PMID- 30212207
TI  - Thermal Decoherence and Disorder Effects on Chiral-Induced Spin Selectivity.
AB  - We use a nonlinear master equation formalism to account for thermal and disorder
      effects on spin-dependent electron transport in helical organic molecules coupled
      to two ideal leads. The inclusion of these two effects has important consequences
      in understanding the observed length and temperature dependence of spin
      polarization in experiments, which cannot be accounted for in a purely coherent
      tunneling model. Our approach considers a tight-binding helical Hamiltonian with
      disordered onsite energies to describe the resulting electronic states when low
      frequency interacting modes break the electron coherence. The high-frequency
      fluctuating counterpart of these interactions, typical of intramolecular modes,
      is included by means of temperature-dependent thermally activated transfer
      probabilities in the master equation, which lead to hopping between localized
      states. We focus on the spin-dependent conductance and the spin-polarization in
      the linear regime (low voltage), which are analyzed as a function of the
      molecular length and the temperature of the system. Our results at room
      temperature agree well with experiments because our model predicts that the
      degree of spin-polarization increases for longer molecules. Also, this effect is
      temperature-dependent because thermal excitation competes with disorder-induced
      Anderson localization. We conclude that a transport mechanism based on thermally
      activated hopping in a disordered system can account for the unexpected behavior
      of the spin polarization.

PMID- 30212208
TI  - An Autonomous Self-Optimizing Flow Reactor for the Synthesis of Natural Product
      Carpanone.
AB  - A modular autonomous flow reactor combining monitoring technologies with a
      feedback algorithm is presented for the synthesis of the natural product
      carpanone. The autonomous self-optimizing system, controlled via MATLAB, was
      designed as a flexible platform enabling an adaptation of the experimental setup
      to the specificity of the chemical transformation to be optimized. The reaction
      monitoring uses either online high pressure liquid chromatography (HPLC) or in
      line benchtop nuclear magnetic resonance (NMR) spectroscopy. The custom-made
      optimization algorithm derived from the Nelder-Mead and golden section search
      methods performs constrained optimizations of black-box functions in a
      multidimensional search domain, thereby assuming no a priori knowledge of the
      chemical reactions. This autonomous self-optimizing system allowed fast and
      efficient optimizations of the chemical steps leading to carpanone. This
      contribution is the first example of a multistep synthesis where all discrete
      steps were optimized with an autonomous flow reactor.

PMID- 30212209
TI  - Application of Reverse Nonequilibrium Molecular Dynamics to the Calculation of
      the Mutual Diffusion Coefficient of Alkane Mixtures.
AB  - In a recent publication, a reverse nonequilibrium molecular dynamics (RNEMD)
      method was presented for computing the mutual diffusion coefficient of liquid
      mixtures. A concentration gradient and a subsequent mass flux are induced in the
      system by suitably exchanging molecules in different regions. The algorithm has
      been successfully tested on Lennard-Jones mixtures and molecular fluid mixtures
      with molecules having the same number of particles. In this work, a modification
      is made to the RNEMD method to determine the mutual diffusion coefficient of
      binary liquid mixtures with molecules having different sizes and masses. To
      migrate molecules of a different type, the splitting method has been used in this
      work. Investigation of the resulting steady-state mass fraction profile allows
      the evaluation of the mutual diffusion coefficient. For validation, the mutual
      diffusion coefficients of ethane-propane and ethane-pentane liquid mixtures at
      different compositions and temperatures have been obtained using this method. The
      mutual diffusion coefficients obtained from the RNEMD simulations are within the
      error bars of values obtained by equilibrium molecular dynamics for the identical
      model and conditions. The excess energy released due to the exchange of molecules
      is efficiently removed by strongly coupling a local thermostat in the region
      around the insertion point. There is no heating of the analysis region.

PMID- 30212210
TI  - Trans and Cis Conformations of the Antihypertensive Drug Valsartan Respectively
      Lock the Inactive and Active-like States of Angiotensin II Type 1 Receptor: A
      Molecular Dynamics Study.
AB  - Angiotensin II type 1 receptor (AT1R) is the principal regulator of blood
      pressure in humans. The overactivation of AT1R by the stimulation of angiotensin
      II would result in high blood pressure. To prevent hypertension, nonpeptide
      "sartan" drugs, such as valsartan (VST), have been developed to competitively
      block the access of angiotensin II to the receptor. Nuclear magnetic resonance
      spectroscopy and molecular modeling studies have identified that VST in solution
      and in lipid micelles (a mimic membrane environment) has two distinct trans/cis
      conformations (VSTtrans/VSTcis) that can be transformed into each other through
      the isomerization of the amide bond. To date, it is still not known whether the
      two conformations of VST can affect the binding of AT1R with VST. To this end,
      the binding of AT1R with VSTtrans or VSTcis was modeled based on the recently
      determined crystal structures of AT1R. Molecular dynamics simulations were then
      performed to study the structural and dynamical differences of AT1R caused by the
      two conformations of VST. Simulation results show that AT1R with VSTtrans has
      higher structural and dynamical stabilities compared to that with VSTcis. Binding
      energy analysis indicates that AT1R bind more strongly with VSTtrans, and the
      energy difference mainly results from the contribution of van der Waals and
      nonpolar interactions. Detailed analyses reveal that unlike AT1R with VSTtrans,
      AT1R with VSTcis displays an activate-like state, which is characterized by a
      small outward movement of transmembrane helix 6. Due to the altered interaction
      with the butyl group of VST, residue Tyr87 undergoes a conformational change that
      causes a contraction of the pocket for VST binding. The rearrangement of AT1R is
      then propagated to the intracellular side of the receptor through the
      conformational change of residue Trp253 (the toggle switch), which results in an
      expansion of the pocket for G protein binding and the breakage of the hydrogen
      bond containing the conserved residue Arg126. These data provide insights into
      the activation mechanism of AT1R caused by the binding of VSTcis, which may help
      to design a new drug to inhibit AT1R and prevent high blood pressure.

PMID- 30212211
TI  - Comparative Studies of the Biosynthetic Gene Clusters for Anthraquinone-Fused
      Enediynes Shedding Light into the Tailoring Steps of Tiancimycin Biosynthesis.
AB  - Comparative analyses of the four known anthraquinone-fused enediynes biosynthetic
      gene clusters identified four genes, tnmE6, tnmH, tnmL, and tnmQ, unique to the
      tnm gene cluster. Larger scale fermentation of both the S. sp. CB03234 wild-type
      and the Delta tnmH and Delta tnmL mutant strains resulted in the characterization
      of 20 new tiancimycin (TNM) congeners, including five enediynes. These findings
      enabled a proposal for the late stage of TNM biosynthesis featuring an
      intermediate possibly common for all anthraquinone-fused enediynes.

PMID- 30212212
TI  - Distinctive Performance of Gemini Surfactant in the Preparation of Hierarchically
      Porous Carbons via High-Internal-Phase Emulsion Template.
AB  - The superior capability of gemini surfactant (GS) in the preparation of
      hierarchically porous carbons via high-internal-phase emulsion (HIPE) template
      followed by pyrolysis was confirmed in this work. Polymerized HIPEs (polyHIPEs)
      of phenol-formaldehyde resin were prepared by cross-linking the continuous phase
      of HIPEs stabilized by GS. Nonionic surfactant and cationic surfactant were also
      selected to stabilize HIPE for comparison. From scanning electron microscope
      observations, polyHIPEs with open-cell pore architectures were obtained with GS
      as emulsifier (polyHIPEs-GS) and the derived carbon foams (carboHIPEs-GS) well
      retained the original pore architectures, whereas polyHIPEs obtained using
      contrastive surfactants showed closed-cell porous structures and notable
      differences were observed for the derived carboHIPEs. Nitrogen
      adsorption/desorption measurements indicated that polyHIPEs-GS and carboHIPEs-GS
      both exhibited hierarchically porous architectures with much higher surface areas
      (SA) than those of the corresponding contrast samples. Mercury intrusion
      porosimetry results indicated that carboHIPEs-GS possessed higher SA and higher
      porosity than that of the contrast samples. The open-cell pore architecture and
      high SA are favorable to many applications, like energy storage. carboHIPE-GS
      expectably showed a higher capacitance than that of contrast samples when used as
      the electrode material of supercapacitor.

PMID- 30212213
TI  - Charge Mobility and Dynamics in Spin-Crossover Nanoparticles Studied by Time
      Resolved Microwave Conductivity.
AB  - We use the electrodeless time-resolved microwave conductivity (TRMC) technique to
      characterize spin-crossover (SCO) nanoparticles. We show that TRMC is a simple
      and accurate means for simultaneously assessing the magnetic state of SCO
      compounds and charge transport information on the nanometer length scale. In the
      low-spin state from liquid nitrogen temperature up to 360 K the TRMC measurements
      present two well-defined regimes in the mobility and in the half-life times, in
      which the former transition temperature TR occurs near 225 K. Below TR, we
      propose that an activationless regime taking place associated with short
      lifetimes of the charge carriers points at the presence of shallow-trap states.
      Above TR, these states are thermally released, yielding a thermally activated
      hopping regime where longer hops increase the mobility and, concomitantly, the
      barrier energy. The activation energy could originate not only from intricate
      contributions such as polaronic self-localizations but also from dynamic disorder
      due to phonons and/or thermal fluctuations of SCO moieties.

PMID- 30212215
TI  - Probing a Spin Transfer Controlled Magnetic Nanowire with a Single Nitrogen
      Vacancy Spin in Bulk Diamond.
AB  - The point-like nature and exquisite magnetic field sensitivity of the nitrogen
      vacancy (NV) center in diamond can provide information about the inner workings
      of magnetic nanocircuits in complement with traditional transport techniques.
      Here, we use a single NV in bulk diamond to probe the stray field of a
      ferromagnetic nanowire controlled by spin transfer (ST) torques. We first report
      an unambiguous measurement of ST tuned, parametrically driven, large-amplitude
      magnetic oscillations. At the same time, we demonstrate that such magnetic
      oscillations alone can directly drive NV spin transitions, providing a potential
      new means of control. Finally, we use the NV as a local noise thermometer,
      observing strong ST damping of the stray field noise, consistent with magnetic
      cooling from room temperature to ~150 K.

PMID- 30212214
TI  - FRET Reveals the Formation and Exchange Dynamics of Protein-Containing Complex
      Coacervate Core Micelles.
AB  - The encapsulation of proteins into complex coacervate core micelles (C3Ms) is of
      potential interest for a wide range of applications. To address the stability and
      dynamic properties of these polyelectrolyte complexes, combinations of cyan,
      yellow, and blue fluorescent proteins were encapsulated with cationic-neutral
      diblock copolymer poly(2-methyl-vinyl-pyridinium)128- b-poly(ethylene-oxide)477.
      Forster resonance energy transfer (FRET) allowed us to determine the kinetics of
      C3M formation and of protein exchange between C3Ms. Both processes follow first
      order kinetics with relaxation times of +/-100 s at low ionic strength ( I = 2.5
      mM). Stability studies revealed that 50% of FRET was lost at I = 20 mM, pointing
      to the disintegration of the C3Ms. On the basis of experimental and theoretical
      considerations, we propose that C3Ms relax to their final state by association
      and dissociation of near-neutral soluble protein-polymer complexes. To obtain
      protein-containing C3Ms suitable for applications, it is necessary to improve the
      rigidity and salt stability of these complexes.

PMID- 30212216
TI  - Toward Developing a Predictive Approach To Assess Electron Beam Instability
      during Transmission Electron Microscopy of Drug Molecules.
AB  - During drug development control of polymorphism, particle properties and
      impurities are critical for ensuring a good quality, reproducible, and safe
      medicine. A wide variety of analytical techniques are employed in demonstrating
      the regulators control over the drug substance and product manufacturing,
      storage, and supply. Transmission electron microscopy (TEM) offers the
      opportunity to analyze in detail pharmaceutical systems at a length scale and
      limit of detection not readily achieved by many traditional techniques. However,
      the use of TEM as a characterization tool for drug development is uncommon due to
      possible damage caused by the electron beam. This work outlines the development
      of a model, using molecular descriptors, to predict the electron beam stability
      of active pharmaceutical ingredients (API). For a given set of conditions and a
      particular imaging or analytical mode, the total number of electrons per unit
      area, which causes observable damage to a sample in the TEM, can be defined as
      the critical fluence ( CF). Here the CF of 20 poorly water-soluble APIs were
      measured using selected area electron diffraction. Principal component analysis
      was used to select the most influential molecular descriptors on CF, which were
      shown to be descriptors involving the degree of conjugation, the number of
      hydrogen bond donors and acceptors, and the number of rotatable bonds. These were
      used to generate several multiple linear regression models. The model that
      provided the best fit to the measured CF data included the ratio of the number of
      conjugated carbons to nonconjugated carbons, the ratio of the number of hydrogen
      bond donors to acceptors, and the ratio of the number of hydrogen bond acceptors
      to donors. Using this model, the CF of the majority of the compounds was
      predicted within +/-2 e-/A2. Molecules with no hydrogen bond acceptors did not
      fit the model accurately possibly due to the limited sample size or the influence
      of other parameters not included in this model, such as intermolecular bond
      energies. The model presented can be used to support pharmaceutical development
      by quickly assessing the stability of other poorly soluble drugs in TEM. Provided
      that the model suggests that the API is relatively stable to electron
      irradiation, TEM offers the prospect of determining the presence of crystalline
      material at low levels at length scales and limits of detection unobtainable by
      other techniques. This is particularly so for amorphous solid dispersions.

PMID- 30212217
TI  - Bioinspired Synthesis of Pygmaeocins and Related Rearranged Abietane Diterpenes:
      Synthesis of Viridoquinone.
AB  - A bioinspired synthesis of rearranged abietane diterpenes, related to
      pygmaeocins, is described. In this process, the key step is the 1,2-migration of
      the C-20 angular methyl to the C-5 position of the abietane skeleton, which
      occurs when a C6-C7 unsaturated dehydroabietane derivative is treated with SeO2
      in dioxane under reflux (19 examples for this rearrangement are described).
      Utilizing this reaction, an enantiospecific synthesis of pygmaeocin C and the
      first synthesis of viridoquinone, starting from the abietane phenol ferruginol,
      are reported. A tentative mechanism for this reaction and a possible biosynthetic
      pathway for this family of metabolites are postulated.

PMID- 30212218
TI  - Nanostructured Bi Grown on Epitaxial Graphene/SiC.
AB  - Controllable growth of metal nanostructures on epitaxial graphene (EG) is
      particularly interesting and important for the applications in electric devices.
      Bi nanostructures on EG/SiC are fabricated through thermal decomposition of SiC
      and subsequent low-flux evaporation of Bi. The orientation, atomic structure, and
      thickness-dependent electronic states of Bi are investigated by scanning
      tunneling microscopy/spectroscopy. It is found that metallic Bi nanoflakes and
      nanorods prefer to grow on the SiC buffer layer region with higher diffusion
      barrier, but Bi nanoribbons are formed on regularly ordered EG. Although the
      thicker Bi nanoribbons of 11 monolayers on EG are still metallic, the thinner
      ones become semiconducting owing to the interfacial effect. This indicates that
      the electronic states and physical properties of Bi are substrate-dependent. The
      results are helpful for the design of Bi- and graphene-based electronic and
      spintronic devices.

PMID- 30212219
TI  - Surface Potential of a Planar Charged Lipid-Water Interface. What Do Vibrating
      Plate Methods, Second Harmonic and Sum Frequency Measure?
AB  - The interfacial electrical potential is an important parameter influencing, for
      instance, electrochemical reactions and biomolecular interactions at membranes. A
      deeper understanding of different methods that measure quantities related to the
      surface potential is thus of great scientific and technological relevance. We use
      lipid monolayers with varying charge density and thoroughly compare the results
      of surface potential measurements performed with the vibrating plate capacitor
      method and second harmonic generation spectroscopy. The two techniques provide
      very different results as a function of surface charge. Using the molecular
      information on lipid alkyl chain, lipid headgroup, and interfacial water provided
      by sum frequency generation spectroscopy, we disentangle the different
      contributions to the surface potential measured by the different techniques. Our
      results show that the two distinct approaches are dominated by different
      molecular moieties and effects. While the shape of the SPOT method response as a
      function of charge density is dominated by the lipid carbonyl groups, the SHG
      results contain contributions from the interfacial water molecules, the lipids
      and hyper-Rayleigh scattering.

PMID- 30212220
TI  - Nitrilotriacetic Acid-Functionalized Glucose-Responsive Complex Micelles for the
      Efficient Encapsulation and Self-Regulated Release of Insulin.
AB  - Insulin plays a significant role in diabetes treatment. Although a huge number of
      insulin-loaded, glucose-responsive nanocarriers have been developed in past
      decades, most of them showed a lower loading capacity and efficiency due to the
      weak interaction between insulin and nanocarriers. In this work, a novel insulin
      encapsulated glucose-responsive polymeric complex micelle (CM) is devised,
      showing (i) enhanced insulin-loading efficiency owing to the zinc ions' chelation
      by nitrilotriacetic acid (NTA) groups of NTA-functioned glycopolymer and the
      histidine imidazole of insulin, (ii) the glucose-triggered pulse release of
      insulin, and (iii) long stability under physiological conditions. This CM was
      fabricated by the self-assembly of block copolymer PEG- b-P(Asp- co-AspPBA) and
      glycopolymer P(Asp- co-AspGA- co-AspNTA), resulting in complex micelles with a
      PEG shell and a cross-linked core composed of phenylboronic acid (PBA)/glucose
      complexations. Notably, the modified nitrilotriacetic acid (NTA) groups of CM
      could specifically bind insulin via chelated zinc ions, thus enhancing the
      loading efficacy of insulin compared to that of nonmodified CM. The dynamic
      PBA/glucose complexation core of CM dissociates under the trigger of high glucose
      concentration (>2 g/L) while being quite stable in low glucose concentrations (<2
      g/L), as demonstrated by the pulse release of insulin in vitro. Finally, in a
      murine model of type 1 diabetes, NTA-modified complex micelles loading an insulin
      (NTA-CM-INS) group exhibited a long hypoglycemic effect which is superior to that
      of free insulin in the PBS (PBS-INS) group and insulin-loaded complex micelles
      without an NTA modification (CM-INS) group. This long-term effect benefited from
      Zn(II) chelation by NTA-modified complex micelles and could avoid hypoglycemia
      caused by the burst release of insulin. Taken together, this constitutes a highly
      effective way to encapsulate insulin and release insulin via an on-demand manner
      for blood glucose control in diabetes.

PMID- 30212221
TI  - Self-Assembly of Metallacages into Multidimensional Suprastructures with Tunable
      Emissions.
AB  - Cubic metallacages were arranged into multidimensional (one-, two-, and three
      dimensional) suprastructures via multistep assembly. Four new shape-controllable,
      hybrid metallacages with modified substituents and tunable electronic properties
      were prepared using dicarboxylate ligands with various substituents (sodium
      sulfonate, nitro, methoxyl, and amine), tetra-(4-pyridylphenyl) ethylene, and cis
      (PEt3)2Pt(OTf)2. The as-prepared metallacages were used as building blocks for
      further assembly. Diverse suprastructures with tunable emissions (lambdamax from
      451 to 519 nm) and various substituents (-SO3Na, -NO2, -OCH3, and -NH2) were
      prepared depending on the substituents and solvents used.

PMID- 30212222
TI  - Spectroscopy of Molecular Ions in Coulomb Crystals.
AB  - In this Perspective, we examine the use of laser-cooled atomic ions and
      sympathetically cooled molecular ions in Coulomb crystals for molecular
      spectroscopy. Coulomb crystals are well-isolated environments that provide
      localization and long storage times for sensitive measurements of weak signals
      and cold temperatures for precise spectroscopy. Coulomb crystals of molecular and
      atomic ions enable the detection of single-photon molecular ion transitions at a
      range of wavelengths by a change in atomic ion fluorescence at visible
      wavelengths. We give an overview of the state of the art from action spectroscopy
      to quantum logic spectroscopy for a wide range of molecular transitions from
      rotational sublevels separated by 10-7 cm-1 to rovibronic transitions at 25 000
      cm-1. We emphasize how this system allows for unparalleled control of the
      molecular ion state for precision spectroscopy with applications in
      astrochemistry and fundamental physics. We conclude with an outlook of the use of
      this control in cold molecular ion reactions.

PMID- 30212223
TI  - Organocatalytic Dearomative [4 + 2] Cycloadditions of Biomass-Derived 2,5
      Dimethylfuran with ortho-Quinone Methides: Access to Multisubstituted Chromanes.
AB  - The organocatalytic dearomative [4 + 2] cycloadditions of biomass-derived 2,5
      dimethylfuran with ortho-quinone methides were developed, affording two
      diffferent types of multisubstituted chromanes in high yields and excellent
      diastereoselectivities. The controllable synthesis of these two types of
      multisubstituted chromanes could be achieved by succinctly varying the reaction
      conditions.

PMID- 30212224
TI  - Advances in the pharmacotherapeutic management of dementia with Lewy bodies.
AB  - INTRODUCTION: Dementia with Lewy bodies (DLB) is the second most common type of
      dementia in people over 65 years of age. Given the complex clinical phenotype,
      the management of DLB may be challenging, especially considering that there is
      limited evidence about specific interventions, and there are currently no Food
      and Drug Administration (FDA)/European Medicines Agency (EMA)-approved
      medications. Areas covered: This article provides an overview of the current
      pharmacotherapy in DLB and gives review to the most recent drug candidates in
      clinical trials. Expert opinion: Commonly prescribed drugs are primarily aimed at
      treating the most troublesome clinical features of DLB. Although these
      medications provide some benefit to symptoms, there is, unfortunately, a lack of
      DLB-specific evidence on effective treatments and their off-label use. Indeed,
      most treatments used come from clinical trials on patients with Alzheimer's
      disease or Parkinson's disease. Thus, there is an urgent need for randomized
      clinical trials in DLB patients. Despite several challenges, potential new drugs
      are in ongoing clinical trials; furthermore, as our understanding of molecular
      and cellular mechanisms underlying DLB broaden, it is likely that we will
      identify novel drug targets for the development of better and more effective
      symptomatic products and disease-modifying therapies.

PMID- 30212225
TI  - Black Race and Body Mass Index Are Risk Factors for Rhabdomyolysis and Acute
      Kidney Injury in Trauma.
AB  - PURPOSE: Obesity has been shown in a single-center study to be a risk factor for
      rhabdomyolysis. More recently, sickle cell trait, known to be more prevalent in
      blacks, has been shown to be a risk factor for rhabdomyolysis. We hypothesized
      that in trauma patients, black race and a higher body mass index (BMI) are
      associated with risk for rhabdomyolysis and acute kidney injury (AKI). MATERIALS
      AND METHODS: The National Trauma Data Bank (NTDB) was queried (2013-2015) to
      identify patients age >=18 years and grouped by BMI: normal (18.5-24.99 kg/m2),
      underweight (16.5-18.49 kg/m2), overweight (25-29.99 kg/m2), obese (30-34.99
      kg/m2), severely obese (35-39.99 kg/m2), and morbidly obese (>=40 kg/m2). A
      multivariable logistic regression model was used to assess whether a higher BMI
      or black race was associated with rhabdomyolysis or AKI. RESULTS: After adjusting
      for covariates, severe obesity (odds ratio (OR) = 1.42, confidence interval (CI)
      = 1.01-1.99, p < .001), morbid obesity (OR = 1.46, CI = 1.04-2.06, p < .001), and
      black race (OR = 1.52, CI = 1.24-1.88, p < .001) were associated with higher risk
      for rhabdomyolysis. Patients that were overweight (OR = 1.17, CI = 1.11-1.24, p <
      .001), obese (OR = 1.32, CI = 1.24-1.41, p < .001), severely obese (OR = 1.72, CI
      = 1.59-1.86, p < .001), morbidly obese (OR = 1.77, CI = 1.64-1.92, p < .001), or
      black (OR = 1.31, CI = 1.24-1.38, p < .001) were associated with higher risk for
      AKI. CONCLUSIONS: Black race was associated with an increased risk of
      rhabdomyolysis as well as AKI in trauma. BMI >=25 kg/m2 was associated with
      increased risk for AKI with the morbidly obese having the highest risk. BMI >=35
      kg/m2 was found to be associated with increased risk of rhabdomyolysis. Future
      studies should investigate the role for routine screening of these high-risk
      populations and other potential associated factors such as adherence to weight
      based fluid resuscitation.

PMID- 30212226
TI  - Effects of the Endocrine-Disrupting Chemicals, Vinclozolin and Polychlorinated
      Biphenyls, on Physiological and Sociosexual Phenotypes in F2 Generation Sprague
      Dawley Rats.
AB  - BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs) during gestation
      influences development of the F1 generation offspring and can result in disease
      and dysfunction in adulthood. Limited evidence suggests consequences on the F2
      generation, exposed as germ cells within the F1 fetus. These F2s provide a unique
      window into the programming effects of EDCs. OBJECTIVE: This study assessed
      intergenerational effects of EDC exposure on adult physiology and behavior in
      Sprague-Dawley rats. METHODS: Pregnant rats were exposed to either a
      polychlorinated biphenyl (PCB) mixture, Aroclor 1,221 (A1221), the fungicide
      vinclozolin (VIN), or the vehicle (VEH) (6% dimethylsulfoxide in sesame oil)
      alone. A1221 is weakly estrogenic, while VIN is antiandrogenic, enabling us to
      compare different classes of EDCs. The F1 male and female offspring were bred to
      generate the paternal- and maternal-lineage F2 generation. This F2 generation was
      assessed for physiological outcomes, ultrasonic vocalizations (USVs), and sexual
      behavior in adulthood. RESULTS: Each EDC caused phenotypic effects in a sex- and
      lineage-dependent manner. The most robustly affected group was the paternal
      lineage males. F2 VIN paternal male descendants had increased body weight
      throughout the lifespan, lower concentrations of circulating estradiol, and lower
      adrenal and testicular indices. Both VIN and A1221 paternal-lineage males also
      exhibited the greatest number of changes in the characteristics of USVs in
      response to an opposite-sex animal and changes in sexual behaviors in a mating
      test. CONCLUSION: Exposure of rats to EDCs at the germ cell stage led to
      differences in the physiological and behavioral phenotype later in life,
      especially in males. This finding has implications for multigenerational
      physiological and reproductive health in wildlife and humans.
      https://doi.org/10.1289/EHP3550.

PMID- 30212227
TI  - Cilostazol for treatment of cerebral infarction.
AB  - INTRODUCTION: Stroke not only causes critical disability and death but is also a
      cause of anxiety with the possibility of secondary cardiovascular events
      including secondary ischemic stroke. Indeed, patients with a history of previous
      stroke have a high rate of stroke recurrence, indicating the clinical importance
      of secondary stroke prevention. Area of covered: This review provides an overview
      of the pooled evidence for cilostazol's use in the management of secondary stroke
      prevention. Among the various antiplatelet agents that are available, aspirin is
      the most frequently used agent worldwide for the prevention of secondary stroke.
      Cilostazol, a selective phosphodiesterase (PDE) 3A inhibitor, is used worldwide
      for the treatment of patients with intermittent claudication. However, in Asia,
      cilostazol is recommended and used in practice for secondary stroke prevention.
      Expert opinion: The authors believe that cilostazol could be used for secondary
      stroke prevention not only in Asia but worldwide. However, further randomized
      trials on cilostazol are needed, especially in the US and Europe to better
      support its case.

PMID- 30212228
TI  - Time-related eating patterns and chronotype are associated with diet quality in
      pregnant women.
AB  - Animal studies strongly suggest that timed feeding can have beneficial
      physiological effects, including protection against the obesogenic and metabolic
      consequences of a high-fat diet. However, the relationship between variables
      related to the timing of eating and diet quality in pregnancy women, which is
      considered as a period of nutritional vulnerability, is still poorly described in
      the literature. Therefore, the aim of the present study was to investigate the
      associations between time-related eating patterns and chronotype with diet
      quality of pregnant women. This cross-sectional study was conducted with 100
      pregnant women in the first gestational trimester (<=12 weeks of gestation). The
      information regarding food intake was obtained by three 24-Hour Dietary Recall
      (24HR). Time-related eating patterns, i.e., the interval between the first and
      the last meal (eating duration), nightly fasting, time of the first and last
      meals, and number of meals eating on a day were determined. Chronotype was
      derived using the mid-sleep time on free days on weekends, with a further
      correction for calculated sleep debt. Diet quality was evaluated using the
      Brazilian Healthy Eating Index-Revised (BHEI-R), validated for the Brazilian
      population. Linear regression modeling analyses adjusted for confounders were
      used to investigate the association between time-related eating patterns and
      chronotype with diet quality. The BHEI-R total score was negatively associated
      with time of the first meal (beta =  -0.355; p = 0.002; r2 adjusted = 0.141), and
      positively associated with eating duration (beta = 0.262; p = 0.024; r2 adjusted
      = 0.086) and number of meals (beta = 0.273; p = 0.019; r2 adjusted = 0.091). In
      addition, the score of total fruit component was negatively associated with
      chronotype (beta = -0.236; p = 0.033; r2 adjusted = 0.078), time of the first
      meal (beta = -0.393; p = 0.001; r2 adjusted = 0.171), and positively associated
      with eating duration (beta = 0.259; p = 0.022; r2 adjusted = 0.087) and number of
      meals (beta = 0.376; p = 0.001; r2 adjusted = 0.159). The score for whole fruit
      component was negatively associated with time of the first meal (beta = -0.388; p
      = 0.001; r2 adjusted = 0.152), and positively associated with number of meals
      (beta = 0.403; p = 0.001; r2 adjusted = 0.164). A longer eating duration, earlier
      time of the first meal, higher number of meals and morningness tendency are
      associated with a better diet quality in the first gestational trimester - higher
      scores of the total BHEI-R and/or fruit components. We suggest that nutritional
      guidelines should consider time-related eating patterns and chronotype to ensure
      good diet quality of pregnant women since the beginning of gestation,
      contributing on prevention of metabolic-nutritional complications.

PMID- 30212229
TI  - Microbial Quality of Agricultural Water Used in Produce Preharvest Production on
      the Eastern Shore of Virginia.
AB  - Several produce-borne outbreaks have been associated with the use of contaminated
      water during preharvest applications. Salmonella has been implicated in a number
      of these outbreaks. The purpose of this study was to evaluate the microbial
      quality of agricultural surface water used in preharvest production on the
      Eastern Shore of Virginia in accordance with the Food Safety Modernization Act's
      Produce Safety Rule water standards. The study also examined the prevalence,
      concentration, and diversity of Salmonella in those water sources. Water samples
      (1 L) from 20 agricultural ponds were collected during the 2015 and 2016 growing
      seasons ( n = 400). Total aerobic bacteria, total coliforms, and Escherichia coli
      were enumerated for each sample. Population levels of each microorganism were
      calculated per 100-mL sample and log transformed, when necessary. Samples (250
      mL) were also enriched for Salmonella. Presumptive Salmonella isolates were
      confirmed by PCR ( invA gene) and were serotyped. In 2016, the concentration of
      Salmonella in each sample was also estimated by most probable number (MPN).
      Indicator bacteria and environmental and meteorological factors were analyzed for
      their association with the detection of a Salmonella-positive water sample by
      using logistic regression analysis. Seventeen of the 20 ponds met the Food Safety
      Modernization Act's Produce Safety Rule standards for production agricultural
      water. Three ponds did not meet the standards because the statistical threshold
      value exceeded the limit. Salmonella was detected in 19% of water samples in each
      year (38 of 200 in 2015 and 38 of 200 in 2016). Of the 118 Salmonella isolates
      serotyped, 14 serotypes were identified with the most prevalent being Salmonella
      Newport. E. coli concentration, farm, and total aerobic bacteria concentration
      were significantly associated with the likelihood of detecting a Salmonella
      positive sample The average concentration of Salmonella in all samples was 4.44
      MPN/100 mL, with the limit of detection being 3.00 MPN/100 mL. The highest
      concentration of Salmonella was 93.0 MPN/100 mL. These data will assist in a
      better understanding of the risks that production water poses to produce
      contamination events.

PMID- 30212230
TI  - Anterior Iliac Spine Avulsion Fracture Treatment Options in Young Athletes.
AB  - PURPOSE: The aim of this research is to perform a literature review of the
      treatments available for the anterior iliac spines avulsion fracture on the young
      subjects. MATERIAL AND METHODS: We performed a systematic literature search for
      studies on spines avulsion fractures in young subjects from January 1, 2013, to
      February 2018; abstracts were screened by a single reviewer. For those studies
      meeting the eligibility criteria, full-text articles were obtained. RESULTS: From
      112 studies found only six articles were included in this systematic review. All
      the studies belonged to level IV of scientific evidence. 64 patients suffered an
      anterior inferior iliac spine fracture while patients 36% patients suffered an
      anterior superior iliac spine fracture. 93.2% underwent conservative treatment
      and 6.8% underwent surgery. CONCLUSIONS: The anterior iliac spine avulsions
      fractures are rare injuries that occur in young male athletes and the
      conservative option is the most selected treatment modality.

PMID- 30212231
TI  - Chronotype and energy intake timing in relation to changes in anthropometrics: a
      7-year follow-up study in adults.
AB  - Individuals with a later preference for the daily activities (evening types) tend
      to have unhealthier behaviors, which could increase their risk for obesity when
      compared those with an earlier preference (morning types). Furthermore, later
      food intake timing, another behavior more characteristic of evening types, has
      been associated with obesity. However, chronotype differences in the long-term
      weight change and the role of chronotype in the association between energy intake
      timing and obesity risk are not clear. To study this we first examined the
      independent associations of chronotype and energy intake timing with
      anthropometric changes and then whether chronotype modified the association
      between energy intake timing and obesity risk. Our data included 1097 Finns from
      DILGOM (DIetary Lifestyle and Genetic Determinants of Obesity and Metabolic
      syndrome) 2007 (baseline) and 2014 (follow-up) and from Findiet 2007. Chronotype
      was assessed with a shortened version of Horne and Ostberg's morningness
      eveningness questionnaire. Energy intake timing (as percentages of the total
      energy intake in the morning/evening) was assessed with 48-h dietary recalls.
      Weight, body mass index (BMI), and waist circumference were based on measured and
      self-reported values. Analysis of co-variance and multivariable logistic
      regression models were used for statistical analyses. Evening typed women had
      greater weight gain (+ 2.3 kg vs. + 0.3 kg, P = 0.016) and increase in BMI (0.7
      kg/m2 vs. -0.1 kg/m2, P = 0.024) than morning typed women. After excluding
      participants with depression, these associations attenuated to non-significant.
      Compared to participants whose energy intake was proportionally lowest during
      evening, those with proportionally highest energy intake during evening were more
      likely with obesity (BMI>= 30 kg/m2) after follow-up (OR 1.97, 95% CI 1.21-3.21,
      Ptrend = 0.042). Participants' chronotype did not modify this association
      (Pinteract = 0.95). In conclusion, our findings indicated that evening energy
      intake may play a role in obesity regardless of the chronotype. Furthermore,
      evening typed women were more prone to increases in their anthropometrics, which
      seem to be at least partly explained by depression. Further studies of this topic
      are warranted.

PMID- 30212232
TI  - The Clearance of High-Risk Human Papillomavirus is Sooner After Thin Loop
      Electrosurgical Excision Procedure (t-LEEP).
AB  - : Purpose/aim of the study: To investigate high-risk human papillomavirus (HPV)
      infection clearance following thin loop electrosurgical excision procedure (t
      LEEP) among patients with cervical benign lesion. MATERIALS AND METHODS: This
      retrospective study analyzed clinical data from patients with cervical benign
      lesion and HPV infection, who had undergone t-LEEP (T-Group), compared with
      patients with HPV infection undergone no treatment (NT-Group). Both groups
      attended regular follow-up between January 2008 and January 2012. Kaplan-Meier
      analysis was used to compare the HPV clearance time. RESULTS: The average
      clearance time was 7.7 months (M) (95% confidence interval [CI]: 6.5-8.9 M) in T
      Group, and 10.4 M (95%CI: 9.4-11.3 M) in NT-Group, with significant difference
      between groups (p = 0.003). Among patients with low viral load, the HPV clearance
      times were 7.6 M (95%CI: 6.3-9.0 M) in T-Group and 9.7 M (95%CI: 8.6-10.8 M) in
      NT-Group (p = 0.042). Among patients with high viral load, the HPV clearance
      times were 8.0 M (95%CI: 5.3-10.6 M) in T-Group and 11.4 M (95%CI: 9.7-13.1 M) in
      NT-Group (p = 0.041). The average time of HPV clearance in T-Group was shorter
      than NT-Group in all age groups, with significant differences in <=29Y-group (p =
      0.008) and 30-39Y-group (p = 0.005). The accumulated clearance rate of HPV
      infection at sixth month and 12th month were 24.5% and 67.9% in T-Group, 7.8% and
      43.1% in NT-Group, with significant differences (p = 0.001 at 6th month, p =
      0.032 at 12th month). CONCLUSIONS: T-LEEP accelerates the clearance of high-risk
      HPV infection and make the HPV infection rates dropped rapidly in the first year.

PMID- 30212233
TI  - Timing of food intake is more potent than habitual voluntary exercise to prevent
      diet-induced obesity in mice.
AB  - : Inappropriate eating habits such as skipping breakfast and eating late at night
      are associated with risk for abnormal weight-gain and adiposity. We previously
      reported that time-imposed feeding during the daytime (inactive phase) induces
      obesity and metabolic disorders accompanied by physical inactivity in mice. The
      present study compares metabolic changes induced in mice by time-imposed feeding
      under voluntary wheel-running (RW) and sedentary (SED) conditions to determine
      the effects of voluntary wheel-running activity on obesity induced in mice by
      feeding at inappropriate times. Mice were individually housed in cages with or
      without running-wheels. We compared food consumption, core body temperature,
      hormonal and metabolic variables in the blood, lipid accumulation in the liver,
      circadian expression of clock and metabolic genes in peripheral tissues, and
      gains in body weight between mice allowed access to food only during the sleep
      phase (daytime feeding; DF) or only during the active phase (nighttime feeding;
      NF) under SED or RW conditions. Only a high-fat high-sucrose diet was available
      to the mice throughout restricted feeding. Nocturnal activity was maintained in
      both NF and DF mice under RW conditions, but significantly suppressed during the
      latter half of the dark phase in DF mice. Nocturnal fluctuations in core body
      temperature were maintained in DF and NF mice under both SED and RW conditions,
      although DF attenuated the day-night amplitude more under SED, than RW
      conditions. The degrees of DF-induced increases in body weight gain, food
      efficiency, adipose tissue mass, lipogenic gene expression in metabolic tissues,
      and hepatic lipid accumulation were essentially identical between SED and RW
      conditions. Daytime feeding also induced hyperinsulinemia and hyperleptinemia
      under both SED and RW conditions, although DF-induced hyperleptinemia was
      slightly attenuated by wheel-running. The temporal expression of circadian clock
      genes became synchronized to feeding cycles in the liver but not in the skeletal
      muscle of mice under both SED and RW conditions. Chronic voluntary exercise on
      running-wheels minimally affected obesity and adiposity in mice caused by daily
      feeding at unusual times. The timing of food intake might be more important than
      physical exercise for preventing metabolic disorders. ABBREVIATIONS: ANOVA:
      analysis of variance; DF: daytime feeding; FFA: free fatty acid; GLP-1: glucagon
      like peptide-1; HOMA-IR: homeostasis model assessment of insulin resistance;
      NEAT: non-exercise activity thermogenesis; NF: nighttime feeding; RF: restricted
      feeding; RW: running-wheel; SCN: suprachiasmatic nucleus; SE: standard error of
      the mean; SED: sedentary; SPA: spontaneous physical activity; T-Cho: total
      cholesterol; TG: triglyceride; WAT: white adipose tissues.

PMID- 30212234
TI  - Assessment of Evidence-Based Health and Safety Policies on Sudden Death and
      Concussion Management in Secondary School Athletics: A Benchmark Study.
AB  - CONTEXT: : Implementation of best-practice health and safety policies has been
      shown to be effective at reducing the risk of sudden death in sport; however,
      little is known about the extent to which these policies are required within
      secondary school athletics. OBJECTIVE: : To examine best-practice health and
      safety policies pertaining to the leading causes of sudden death and to
      concussion management in sport mandated at the state level for secondary school
      athletics. DESIGN: : Descriptive observational study. SETTING: : State high
      school athletic associations (SHSAAs), state departments of education, and
      enacted legislation. PATIENTS OR OTHER PARTICIPANTS: : United States (including
      the District of Columbia) SHSAAs. MAIN OUTCOME MEASURE(S): : A review of SHSAA
      health and safety policies for the 2016-2017 academic year, state department of
      education policies, and enacted legislation was undertaken to assess the polices
      related to the leading causes of sudden death and concussion management in sport.
      Current best-practice recommendations used to assess health and safety policies
      were specific to emergency action plans, automated external defibrillators, heat
      acclimatization, environmental monitoring and modification, and concussion
      management. The total number of best-practice recommendations required for each
      SHSAA's member schools for the aforementioned areas was quantified and presented
      as total number and percentage of recommendations required. RESULTS: : Four of 51
      SHSAA member schools were required to follow best practices for emergency action
      plans, 7 of 51 for access to automated external defibrillators, 8 of 51 for heat
      acclimatization, and 3 of 51 for management of concussion. CONCLUSIONS: : At the
      time of this study, SHSAA member schools were not required to follow all best
      practice recommendations for preventing the leading causes of sudden death and
      for concussion management in sport. Continued advocacy for the development and
      implementation of best practices at the state level to be required of all
      secondary schools is needed to appropriately serve the health and well-being of
      our young student-athletes.

PMID- 30212235
TI  - Contrast Baths, Intramuscular Hemodynamics, and Oxygenation as Monitored by Near
      Infrared Spectroscopy.
AB  - CONTEXT: : Contrast baths (CB) is a thermal treatment modality used in sports
      medicine, athletic training, and rehabilitation settings. Proposed physiological
      effects of CB include increasing tissue blood flow and oxygenation and decreasing
      tissue swelling and edema to promote better healing, improved limb function, and
      quicker recovery. OBJECTIVE: : To investigate the physiological effects of CB on
      the intramuscular hemodynamics and oxygenation of the lower leg muscles using
      near-infrared spectroscopy (NIRS), an optical method for monitoring changes in
      tissue oxygenated (O2Hb), deoxygenated (HHb), and total hemoglobin (tHb) as well
      as tissue oxygen saturation index (TSI%). DESIGN: : Descriptive laboratory study.
      PATIENTS OR OTHER PARTICIPANTS: : Ten healthy men and women with a mean age of 29
      (range = 17 +/- 42) years, mean body mass index of 24.6 +/- 3.2, and mean adipose
      tissue thickness of 6.4 +/- 2.2 mm. INTERVENTION(S): : Conventional CB (10-minute
      baseline, 4 : 1-minute hot : cold ratio) was applied to the left lower leg. MAIN
      OUTCOME MEASURE(S): : Changes in chromophore concentrations of O2Hb, HHb, tHb,
      and TSI% of the gastrocnemius muscle were monitored during 10 minutes of baseline
      measurement, a 30-minute CB protocol, and 10 minutes of recovery using a
      spatially resolved NIRS. RESULTS: : After a 30-minute CB protocol, increases ( P
      < .05) in tissue O2Hb (7.4 +/- 4 MUM), tHb (7.6 +/- 6.1 MUM), and TSI% (3.1% +/-
      2.3%) were observed as compared with baseline measures. CONCLUSIONS: :
      Application of CB induced a transient change in the hemodynamics and oxygenation
      of the gastrocnemius muscle in healthy individuals. The effect of CB application
      in improving tissue hemodynamics and oxygenation may, therefore, support the
      therapeutic benefits of CB in the treatment of muscle injuries.

PMID- 30212236
TI  - Somatic Mutagenesis in Mammals and Its Implications for Human Disease and Aging.
AB  - DNA mutations as a consequence of errors during DNA damage repair, replication,
      or mitosis are the substrate for evolution. In multicellular organisms, mutations
      can occur in the germline and also in somatic tissues, where they are associated
      with cancer and other chronic diseases and possibly with aging. Recent advances
      in high-throughput sequencing have made it relatively easy to study germline de
      novo mutations, but in somatic cells, the vast majority of mutations are low
      abundant and can be detected only in clonal lineages, such as tumors, or single
      cells. Here we review recent results on somatic mutations in normal human and
      animal tissues with a focus on their possible functional consequences.

PMID- 30212237
TI  - Immunoglobulin-Like Receptors and Their Impact on Wiring of Brain Synapses.
AB  - Synapse formation is mediated by a surprisingly large number and wide variety of
      genes encoding many different protein classes. One of the families increasingly
      implicated in synapse wiring is the immunoglobulin superfamily (IgSF). IgSF
      molecules are by definition any protein containing at least one Ig-like domain,
      making this family one of the most common protein classes encoded by the genome.
      Here, we review the emerging roles for IgSF molecules in synapse formation
      specifically in the vertebrate brain, focusing on examples from three classes of
      IgSF members: ( a) cell adhesion molecules, ( b) signaling molecules, and ( c)
      immune molecules expressed in the brain. The critical roles for IgSF members in
      regulating synapse formation may explain their extensive involvement in
      neuropsychiatric and neurodevelopmental disorders. Solving the IgSF code for
      synapse formation may reveal multiple new targets for rescuing IgSF-mediated
      deficits in synapse formation and, eventually, new treatments for psychiatric
      disorders caused by altered IgSF-induced synapse wiring.

PMID- 30212238
TI  - Assessment of the phenolic content, mutagenicity and genotoxicity of ethanolic
      extracts of stem bark and leaves from Strychnos pseudoquina A. St.-hil.
AB  - Strychnos pseudoquina is a plant species whose stem bark is used as bitter tonic
      beverage. The phytochemical analysis, as well as quantification of phenolic
      constituents and antioxidant activity of ethanolic extracts from S. pseudoquina
      stem bark, and leaves were conducted. The extracts were tested for mutagenicity
      (Ames test) and DNA-damaging activity (Plasmid Cleavage test). Leaves recorded
      the largest amount of flavonoids. The performed high-performance liquid
      chromatography (HPLC) showed flavonoids such as isorhamnetin and
      strychnobiflavone (phytochemical markers of the investigated species) in stem
      barks, but not in leaves. The proanthocyanidin content and antioxidant activity
      were significantly higher in stem barks than in leaves. Stem bark and leaf
      extracts presented mutagenic activity against TA98 and TA100 strains with, and
      without, metabolic activation (S9). The Plasmid Cleavage test did not indicate
      DNA-damaging activity. Our results suggest that extracts deriving from S.
      pseudoquina should be used with extreme caution, mainly the stem bark extract,
      which is widely used in folk medicine.

PMID- 30212239
TI  - Comparison between montelukast and tiotropium as add-on therapy to inhaled
      corticosteroids plus a long-acting beta2-agonist in for patients with asthma.
AB  - OBJECTIVE: Asthma often remains uncontrolled despite treatment with inhaled
      corticosteroids (ICS) alone or with ICS plus a long-acting beta2-agonist (LABA).
      The recommended alternative is the addition of either montelukast or tiotropium.
      The aim of this study was to compare the effects of montelukast and tiotropium on
      airway inflammation and remodeling in persistent asthma. METHODS: Eighty-seven
      patients with asthma were treated with budesonide and formoterol (640/18 MUg);
      then, the patients were randomly allocated to three groups to receive oral
      montelukast (10 mg/day), inhaled tiotropium (5 MUg/day), or no add-on to the
      maintenance therapy for 48 weeks. Fractional exhaled nitric oxide (FeNO) and
      pulmonary function were measured, and quantitative computed tomography was
      performed. RESULTS: Compared to the maintenance therapy, add-on montelukast
      significantly decreased FeNO (p < 0.05) and improved airflow obstruction (p <
      0.05), whereas airway dimensions remained unchanged. Changes in FeNO were
      significantly correlated with changes in FEV1 (r = -0.71, p < 0.001). In
      contrast, the addition of tiotropium significantly decreased airway wall area
      corrected for body surface area (WA/BSA) (p < 0.05), decreased wall thickness
      (T/?BSA) (p < 0.05) and improved airflow obstruction (p < 0.05) with no change in
      FeNO. Changes in WA/BSA and T/?BSA were significantly correlated with the change
      in percentage predicted FEV1 (r = -0.84, p < 0.001 and r = -0.59, p < 0.01,
      respectively). CONCLUSIONS: Adding either montelukast or tiotropium to ICS/LABA
      may provide additive benefits with respect to the pulmonary function and airway
      inflammation or remodeling in patients with asthma.

PMID- 30212240
TI  - An Improved Inhaled Mucolytic to Treat Airway Muco-Obstructive Diseases.
AB  - RATIONALE: Airways obstruction with thick, adherent mucus is a pathophysiologic
      and clinical feature of muco-obstructive respiratory diseases, including chronic
      obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF). Mucins,
      the dominant component of mucus, organize into complex polymeric networks via the
      formation of covalent disulfide bonds, which govern the viscoelastic properties
      of the mucus gel. For decades, inhaled N-acetylcysteine (NAC) has been used as a
      mucolytic to reduce mucin disulfide bonds with little, if any, therapeutic
      effects. Improvement of mucolytic therapy requires the identification of NAC
      deficiencies and the development of compounds that overcome them. OBJECTIVES:
      Elucidate the pharmacological limitations of NAC and test a mucin-reducing agent
      candidate in preclinical settings. METHODS: The study used biochemical (e.g.,
      Western blotting, mass spectrometry) and biophysical assays, including
      micro/macrorheology, spinnability, and mucus velocity measurements to test
      compound efficacy and toxicity in in vitro and in vivo models and patient sputa.
      MEASUREMENTS AND MAIN RESULTS: Dithiothreitol (DTT) and a novel mucolytic agent,
      P3001, were directly compared to NAC in vitro and both exhibited superior
      reducing activities. In vivo, P3001 significantly decreased lung mucus burden in
      betaENaC over-expressing mice whereas NAC did not. In NAC-treated CF patients,
      deposited NAC was rapidly cleared from the lungs and was ineffective on sputum
      biophysical properties. In contrast, P3001 acted faster and at lower
      concentrations than NAC, and was more effective than DNase, in CF sputum ex vivo.
      CONCLUSIONS: These results suggest that reducing the viscoelasticity of airway
      mucus is an achievable therapeutic goal with P-3001 class mucolytic agents.

PMID- 30212241
TI  - Preliminary findings for the validity of the Morningness-Eveningness-Stability
      Scale improved (MESSi): Correlations with activity levels and personality.
AB  - Aim of the present study is an additional validation of the Morningness
      Eveningness-Stability Scale improved (MESSi). We screened a total of 97 German
      students using the reduced Morningness-Eveningness Questionnaire (rMEQ) to
      identify a subsample (N = 42) of definite morning and evening types (31% males,
      mean age: 24.8 +/- 5.8 years). The participants provided information about their
      sleep-wake rhythm (diary), personality traits (questionnaire) and experienced
      actigraphic monitoring. Correlations of the MESSi components "Morning affect
      subscale" (MA) (r = 0.91, p < 0.01) and "Eveningness subscale" (r = -0.87, p <
      0.01) with the rMEQ showed good convergent validity. MA was also significantly
      negatively correlated with the acrophase and the midpoint of sleep as measured by
      actigraphy.

PMID- 30212242
TI  - Positional integration of lung adenocarcinoma susceptibility loci with primary
      human alveolar epithelial cell epigenomes.
AB  - AIM: To identify functional lung adenocarcinoma (LUAD) risk SNPs. MATERIALS &
      METHODS: Eighteen validated LUAD risk SNPs (p <= 5 * 10-8) and 930 SNPs in high
      linkage disequilibrium (r2 > 0.5) were integrated with epigenomic information
      from primary human alveolar epithelial cells. Enhancer-associated SNPs likely
      affecting transcription factor-binding sites were predicted. Three SNPs were
      functionally investigated using luciferase assays, expression quantitative trait
      loci and cancer-specific expression. RESULTS: Forty-seven SNPs mapped to putative
      enhancers; 11 located to open chromatin. Of these, seven altered predicted
      transcription factor-binding motifs. Rs6942067 showed allele-specific luciferase
      expression and expression quantitative trait loci analysis indicates that it
      influences expression of DCBLD1, a gene that encodes an unknown membrane protein
      and is overexpressed in LUAD. CONCLUSION: Integration of candidate LUAD risk SNPS
      with epigenomic marks from normal alveolar epithelium identified numerous
      candidate functional LUAD risk SNPs including rs6942067, which appears to affect
      DCBLD1 expression. Data deposition: Data are provided in GEO record GSE84273.

PMID- 30212243
TI  - Reciprocal changes of H3K27ac and H3K27me3 at the promoter regions of the
      critical genes for endometrial decidualization.
AB  - AIM: Decidualization is essential for embryo implantation and placental
      development. We aimed to obtain transcriptome and epigenome profiles for primary
      endometrial stromal cells (ESCs) and in vitro decidualized cells. MATERIALS &
      METHODS: ESCs isolated from human endometrial tissues remained untreated (D0), or
      decidualized for 4 days (D4) and 8 days (D8) in the presence of 8-bromo-cAMP and
      progesterone. RESULTS: Among the epigenetic modifications examined (DNA
      methylation, H3K27ac, H3K9me3 and H3K27me3), the H3K27ac patterns changed most
      dramatically, with a moderate correlation with gene expression changes, upon
      decidualization. Subsets of up- and down-regulated genes upon decidualization
      were associated with reciprocal changes of H3K27ac and H3K27me3 modifications at
      their promoter region, and were enriched with genes essential for decidualization
      such as WNT4, ZBTB16, PROK1 and GREB1. CONCLUSION: Our dataset is useful to
      further elucidate the molecular mechanisms underlying decidualization.

PMID- 30212245
TI  - Can Robots Help Us Manage the Caregiving Crisis?

PMID- 30212244
TI  - The Disappearing Smartphone.

PMID- 30212246
TI  - Facebook Use, Facebook Jealousy, and Intimate Partner Violence Perpetration.
AB  - Social networking sites (SNS) are now deeply ingrained in our interpersonal
      world. Past research has shown various impacts of SNS on intimate relationships,
      from facilitation of relationship initiation to new sources of conflicts between
      romantic partners. In two studies, we examined Facebook-related jealousy as a
      risk factor for the perpetration of intimate partner violence (IPV) in
      adolescents and young adults. In study 1, 1508 participants completed an online
      survey assessing Facebook use, Facebook jealousy, and IPV perpetration. Facebook
      jealousy emerged as a significant mediator of the association between Facebook
      use and IPV. In study 2, we used a dyadic perspective to investigate the joint
      contribution of both partners' Facebook jealousy to IPV perpetration. In a sample
      of 92 youth (46 couples), results showed a significant interaction between own
      and partner Facebook jealousy. More specifically, own Facebook jealousy was
      associated with IPV perpetration only at high levels of partner Facebook
      jealousy. These findings suggest that online behaviors have meaningful
      implications for offline conflicts and aggression in intimate relationships.

PMID- 30212247
TI  - How Does the World Google the Internet, Anxiety, and Happiness?
AB  - This article investigates how the world uses Google, the most popular search
      engine, to look for information about the "Internet" as well as two symptoms of
      emotional well-being, namely "anxiety" and "happiness." Data corresponding to 202
      countries were collected for a period of 5 years from 2013 to 2017 using Google
      Trends, a free surveillance tool that reports data from the search engine. The
      search volume of "Internet" was positively correlated with that of "anxiety" as
      well as "happiness." Furthermore, the article analyzed if the search volumes
      correlated with actual emotional well-being measured using the World Happiness
      Index provided by the United Nations (UN) and the Life Satisfaction Index
      provided by the Organization for Economic Co-operation and Development (OECD).
      The search volume of "anxiety" showed positive correlations with both the
      indices. The results are discussed, and new directions for future research are
      identified.

PMID- 30212248
TI  - Marital Quality, Loneliness, and Internet Infidelity.
AB  - The rapid development of information technology, such as the Internet and social
      networks, lead to an increasing number of online relationships in the world and
      caused some problems for families and society. One of these problems is
      extramarital relationships that occur through the Internet and social networks.
      The purpose of this study was to investigate the relationship between marital
      quality and Internet infidelity by considering the role of loneliness.
      Participants comprised a total of 406 (190 female and 216 male) married persons,
      who responded to Social and Emotional Loneliness Scale for Adults (SELSA-S),
      Internet Infidelity Questionnaire (IIQ), and Revised Dyadic Adjustment Scale
      (RDAS). The structural model showed that marital quality has negative correlation
      with loneliness and online infidelity and loneliness has positive correlation
      with online infidelity. Results also showed that loneliness has a mediating role
      in the relationship between marital quality and online infidelity.

PMID- 30212249
TI  - Social Media and Couples: What Are the Important Factors for Understanding
      Relationship Satisfaction?
AB  - The current study sought to examine specific Facebook behaviors, related to one's
      relationship and their association with relationship satisfaction. Data were
      collected from 115 undergraduates who were in a relationship and had an active
      Facebook account. Participants completed a number of measures focused on their
      relationship and gave the researcher access to their Facebook profiles to record
      the frequency of all posts (comments and status updates), pictures, tags, and
      likes from the previous two weeks. Each of these behaviors was then coded as
      relationship-specific (involving one's partner) or not. Descriptive statistics
      were calculated for each relationship-specific Facebook behavior. A number of
      participants did not include relationship information on their Facebook page.
      Only relationship status and having one's partner in a profile picture were
      significantly associated with relationship satisfaction. The current study is the
      first of its kind to examine the association between relationship-specific
      Facebook behaviors and relationship satisfaction, beyond that of one's
      relationship status or profile photo alone. The results of this study provide an
      initial glimpse into the specific relationship-oriented behaviors that
      individuals engage in on social media. Furthermore, the results provide guidance
      on macro- versus micro-analysis of online behavior for other researchers who are
      examining social media and couples' relationships.

PMID- 30212250
TI  - City4Age: The Ultimate City for the Elderly Population.

PMID- 30212251
TI  - Perioperative Efficiency vs. Quality of Care - Do We Always Have to Choose?
AB  - INTRODUCTION: ATTEMPTS to enforce optimization practices for operating room (OR)
      efficiency are often interpreted as a "pressure for production" which threatens
      patient safety. The aim of this study is to assess if and how improvements in OR
      efficiency affect patient safety and thus the quality of care. METHODS: In an
      attempt to optimize OR efficiency, a new OR management approach "Integrated
      Practice Improvement Solutions" (IPIS) was developed at the Weiler Division of
      Montefiore Medical Center in 2011. IPIS is a flexible managerial system based on
      elements of multiple practice improvement methodologies incorporated into an open
      source framework. It was implemented in 2012. The data presented covers the
      period from 2012 through 2014 when the system was temporarily discontinued due to
      administrative restructuring. Data from 2011 was used as a baseline. The impact
      of IPIS on patient safety and quality of care was assessed based on quality
      improvement and patient safety (QIPS) Committee reports covering the same period
      of time. RESULTS: IPIS implementation resulted in an increase in surgical
      workload by an average of 10.7%, an increase in OR and anesthesia revenues by
      18.5% and 6.9%, respectively, and decreases in turnover time by 15% and overtime
      for the anesthesia staff by 26%. Based on QIPS reports, the total number of
      complications potentially attributable to "production pressure" was 0.25%, 0.2%
      and 0.16% in 2012, 2013 and 2014, respectively compared to 0.21% in 2011 (p =
      0.56). CONCLUSIONS: Gradual implementation of a methodologically structured
      improvement in OR efficiency has no negative impact on patient safety and quality
      of care.

PMID- 30212252
TI  - Eosinophilic Esophagitis - Pathophysiology and its Clinical Implications.
AB  - Eosinophilic Esophagitis is an antigen mediated chronic disease that is distinct
      from gastroesophageal reflux disease. EoE an emerging clinical problem that is
      rapidly growing in incidence and in recognition. It is characterized clinically
      by feeding dysfunction, dysphagia and reflux-like symptoms. Histologically EoE is
      identifiable by a dense epithelial eosinophilic infiltrate. Experimental modeling
      and clinical studies over the last decade have greatly improved our understanding
      of this disease and led to improvements in clinical understanding and the
      assessment of therapeutic options for patients and their clinicians who manage
      this disease. In this review we review the cliniopathologic diagnostic criteria
      and our understanding of EoE as an allergic disease with genetic and
      immunological components in the pathophysiology. We make note of the berth of
      studies defining the importance of the epithelial barrier and discuss the concept
      of barrier function as an initiating or perpetuating factor for this disease. The
      relationship between the symptoms of dysphagia, feeding dysfunction and our
      current knowledge of the underlying pathophysiologic mechanisms of these clinical
      indicators, as well as advances in clinical assessment of decreased esophageal
      distensibility and narrowing in EoE patients. Lastly, therapeutic implications
      relating to the advances that have led to our current understanding of the
      pathophysiology of EoE are explored.

PMID- 30212253
TI  - Associations between the gut microbiota and host responses to high altitude.
AB  - Hypobaric hypoxia, and dietary protein and fat intakes have been independently
      associated with an altered gastrointestinal (GI) environment and gut microbiota,
      but little is known regarding host-gut microbiota interactions at high altitude
      (HA) and the impact of diet macronutrient composition. This study aimed to
      determine the effect dietary protein:fat ratio manipulation on the gut microbiota
      and GI barrier function during weight loss at high altitude (HA), and to identify
      associations between the gut microbiota and host responses to HA. Following sea
      level (SL) testing, 17 healthy males were transported to HA (4300m) and randomly
      assigned to consume provided standard-protein (SP; 1.1g/kg/d, 39% fat) or higher
      protein (HP; 2.1g/kg/d, 23% fat) carbohydrate-matched hypocaloric diets for 22d.
      Fecal microbiota composition and metabolites, GI barrier function, GI symptoms,
      and acute mountain sickness (AMS) severity were measured. Macronutrient intake
      did not impact fecal microbiota composition, had only transient effects on
      microbiota metabolites, and had no effect on increases in small intestinal
      permeability, GI symptoms, and inflammation observed at HA. AMS severity was also
      unaffected by diet, but in exploratory analyses was associated with higher SL
      relative abundance of Prevotella, a known driver of inter-individual variability
      in human gut microbiota composition, and greater microbiota diversity after AMS
      onset. Findings suggest that the gut microbiota may contribute to variability in
      host responses to HA independent of the dietary protein:fat ratio, but should be
      considered preliminary and hypothesis-generating due to the small sample size and
      exploratory nature of analyses associating the fecal microbiota and host
      responses to HA.

PMID- 30212254
TI  - IL-15 regulates fibrosis and inflammation in a mouse model of chronic
      pancreatitis.
AB  - Pancreatitis is an inflammatory disease characterized by the induction of several
      pro-inflammatory cytokines like interleukin (IL)-6, IL-8, IL-1beta, and IL-1.
      Recently, a multifunctional innate cytokine IL-15 has been implicated in the
      protection of several diseases including cancer. Tissue fibrosis is one of the
      major problems to treat successfully chronic pancreatitis pathogenesis.
      Therefore, we tested the hypothesis that rIL-15 treatment may induce innate
      tissue responses and its over-expression will improve the pathogenesis of
      cerulein-induced chronic pancreatitis, associated remodeling and fibrosis. We
      observed atrophy of acinar cells, increased inflammation, and increased
      deposition of perivascular collagen, the up-regulated protein level of TGF-beta1,
      alpha-SMA, and collagen-1 in cerulein-induced chronic pancreatitis in mice.
      Further, we reported that rIL-15 treatment protects mice from the cerulein
      induced chronic pancreatitis pathogenesis including acinar cells atrophy, and
      perivascular accumulation of tissue collagen followed by down-regulation of pro
      fibrotic genes such as TGF-beta1, alpha-SMA, Collagen-1, Collagen-3, and
      Fibronectin in cerulein-induced chronic pancreatitis in mice. Mechanistically, we
      show that IL-15-mediated increase of IFN-Upsilon responsive iNKT cells in the
      blood and tissue protects cerulein-induced pancreatic pathogenesis in mice. Of
      note, a reduced iNKT cells were also observed in the human chronic pancreatitis
      compared to the normal individuals. Taken together, these data suggest that IL-15
      treatment may be a novel therapeutic strategy for treating chronic pancreatitis
      pathogenesis.

PMID- 30212255
TI  - Increased Subsequent Risk of Coronary Heart Disease in Primary Cesarean Delivery
      Women: A Population-Based Cohort Study.
AB  - BACKGROUND: Impacts of delivery modes on the subsequent risk of coronary heart
      disease (CHD) in pregnant women have not been elucidated. MATERIALS AND METHODS:
      Data of women who had undergone cesarean delivery (CD cohort) or vaginal delivery
      (VD cohort) between January 2000 and December 2012 from Taiwan Health Insurance
      Database were analyzed. All subjects were tracked until December 31, 2013. For
      women with multiple deliveries, only the first delivery data were included. Study
      end point was the diagnosis of new-onset CHD after delivery. RESULTS: In total,
      51,765 subjects (CD cohort: n = 17,839; VD cohort: n = 33,926) were included.
      During 1-14 years of follow-up, the incidence rate of new-onset CHD in the CD
      cohort was significantly higher than in the VD cohort (1.3% [231/17,839] vs. 0.8%
      [257/33,926], p < 0.001; effect size: 0.30). Analysis revealed that the
      subsequent risk of CHD in the CD cohort was significantly higher than in the VD
      cohort (adjusted hazard ratio [HR] = 1.28, 95% confidence intervals [CI]: 1.06
      1.55, p = 0.012). We performed sensitivity tests by excluding subjects who had
      undergone CD due to nonmedical reasons from the CD cohort. The remaining subjects
      were named as the *CD cohort. Analysis also revealed a higher subsequent risk of
      CHD in the *CD cohort than in the VD cohort (adjusted HR = 1.32, 95% CI: 1.08
      1.60, p = 0.006). CONCLUSIONS: Women who had undergone primary CD, especially
      those who had undergone CD due to medical reasons, were associated with an ~30%
      higher risk of CHD than those who had undergone VD.

PMID- 30212256
TI  - Perioperative opioids and colorectal cancer recurrence: a systematic review of
      the literature.
AB  - AIM: To summarize the literature on the long-term impact of perioperative opioids
      in colorectal cancer. MATERIALS & METHODS: Combined results from two searching
      strategies in PubMed/MEDLINE (1950-2018), based on a PICO approach; P: Opioid
      influence on cancer-related long-term outcome in patient undergoing colorectal
      surgery; I: Opioid drugs administered in the perioperative period; C: Correlation
      between dose and/or type of opioid with long-term oncologic outcome; O: Disease
      free survival and/or overall survival (OS). RESULTS: Thirteen articles fulfilled
      the predetermined inclusion criteria. Due to the heterogeneity of the different
      studies, a quantitative meta-analysis to sum the evidence was deemed unfeasible.
      CONCLUSION: Our review indicates that there is no conclusive evidence to avoid
      the use of opioids with the goal of reducing the risk of recurrence in colorectal
      cancer.

PMID- 30212257
TI  - Managing chronic pain: are gabapentinoids being misused?

PMID- 30212258
TI  - Military and Veteran Caregivers' Perspectives of Stressors and a Mind-Body
      Program.
AB  - There are over one million post-9/11 military caregivers in the United States who
      face a variety of stressors inherent to caring for an incapacitated loved one.
      Mind-body interventions, such as the Stress Management and Resilience Training
      Relaxation Response Resiliency Program (SMART-3RP), have been shown to reduce
      stress and improve overall health and functioning. The present qualitative study
      aims to explore stressors experienced by military caregivers in their caregiving
      role and to assess attitudes towards the virtual delivery of the SMART-3RP. We
      conducted two focus groups with a total of 13 caregivers [M (SD) age = 41.25
      (11.49); 92% female], and participants subsequently completed a survey on their
      caregiving experiences. Focus groups were conducted remotely via Google Hangouts
      by two doctoral-level clinicians, transcribed verbatim, and coded using inductive
      thematic analysis. Themes related to stressors of caregiving included: logistical
      stressors faced by caregivers, demands of the caregiving role, concerns about
      children, worries about the future, exacerbation of the caregiver's
      physical/mental health concerns, social dynamics, sacrifices made for their
      veteran in the caregiving role, and relationship dynamics between the veteran and
      caregiver. Military caregivers found the SMART-3RP logical and felt as though it
      could be helpful to them. Caregivers expressed interest in a brief, virtual
      version of the SMART-3RP. Using the findings from the current study, we are
      adapting the SMART-3RP to be administered virtually as a podcast-based
      intervention.

PMID- 30212259
TI  - The Variable Southern Ocean Carbon Sink.
AB  - The CO2 uptake by the Southern Ocean (<35 degrees S) varies substantially on all
      timescales and is a major determinant of the variations of the global ocean
      carbon sink. Particularly strong are the decadal changes characterized by a
      weakening period of the Southern Ocean carbon sink in the 1990s and a rebound
      after 2000. The weakening in the 1990s resulted primarily from a southward shift
      of the westerlies that enhanced the upwelling and outgassing of respired (i.e.,
      natural) CO2. The concurrent reduction in the storage rate of anthropogenic CO2
      in the mode and intermediate waters south of 35 degrees S suggests that this
      shift also decreased the uptake of anthropogenic CO2. The rebound and the
      subsequent strong, decade-long reinvigoration of the carbon sink appear to have
      been driven by cooling in the Pacific Ocean, enhanced stratification in the
      Atlantic and Indian Ocean sectors, and a reduced overturning. Current-generation
      ocean models generally do not reproduce these variations and are poorly skilled
      at making decadal predictions in this region. Expected final online publication
      date for the Annual Review of Marine Science Volume 11 is January 3, 2019. Please
      see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30212260
TI  - Planktonic Marine Archaea.
AB  - Archaea are ubiquitous and abundant members of the marine plankton. Once thought
      of as rare organisms found in exotic extremes of temperature, pressure, or
      salinity, archaea are now known in nearly every marine environment. Though
      frequently referred to collectively, the planktonic archaea actually comprise
      four major phylogenetic groups, each with its own distinct physiology and
      ecology. Only one group-the marine Thaumarchaeota-has cultivated representatives,
      making marine archaea an attractive focus point for the latest developments in
      cultivation-independent molecular methods. Here, we review the ecology,
      physiology, and biogeochemical impact of the four archaeal groups using recent
      insights from cultures and large-scale environmental sequencing studies. We
      highlight key gaps in our knowledge about the ecological roles of marine archaea
      in carbon flow and food web interactions. We emphasize the incredible
      uncultivated diversity within each of the four groups, suggesting there is much
      more to be done. Expected final online publication date for the Annual Review of
      Marine Science Volume 11 is January 3, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30212261
TI  - Teaching children with autism to tie their shoes using video prompt-models and
      backward chaining.
AB  - Video-Based Interventions (VBIs) are those that make use of pre-recorded video
      footage to assist in the acquisition of a variety of skills and behaviours. This
      study examined one type of VBI, video prompting, and its effectiveness when
      combined with backward chaining. Prior research suggests that both VBIs and
      backward chaining are effective intervention methods for skill acquisition. Using
      a single-subject multiple baseline design, this experiment expands the current
      literature by thoroughlyexamining backward chaining and a VBI for the acquisition
      of the shoe-tying behavior in children with Autism Spectrum Disorder. The results
      obtained from this study support prior research that VBIs are effective and their
      effectiveness is influenced by a number of factors. We also found that majority
      of the participants were able to retain their newly acquired behaviors one week
      after achieving mastery.

PMID- 30212262
TI  - Hepatitis E Virus infection seroprevalence and the associated risk factors in
      animals raised in Ibadan, Nigeria.
AB  - Hepatitis E (HE) is an important viral hepatitis of global public and livestock
      health, and food security significance due to the ubiquitous distribution,
      multiple transmission route and zoonotic potentials. HE is also endemic in most
      developing countries including Nigeria. This study therefore investigates the
      seroprevalence and associated risk factors of HEV infection in pigs raised in
      Ibadan, Nigeria. Taking an analytical cross-sectional study design, 176 animals
      (comprising 120 pigs, 26 goats, and 30 cattle) were randomly sampled at the
      Bodija Municipal abattoir, Ibadan. Serum samples and demographic information were
      collected for HEV antibody detection (using a commercial recombinant genotype-3
      antigen ELISA kit) and risk factors, respectively. A 57.5% (69/120) HEV
      seroprevalence was reported in the pigs while 0% prevalence was reported in the
      goats and cattle. In the pigs, a significant age-based HEV seropositivity
      difference (chi2 = 5.30; OR = 0.20-0.89; p = 0.02) with a higher seroprevalence
      in the < 6 months (68.42%; 39/57) compared to the > 6 months age group (47.62%;
      20/63) was reported. No significant sex, breed and husbandry system effect on HEV
      seroprevalence was detected in the pigs. This study therefore underscores the
      high HEV seroprevalence and age-based odds of HEV-exposure in pigs in Ibadan,
      Nigeria.

PMID- 30212263
TI  - Antigen binding allosterically promotes Fc receptor recognition.
AB  - A key question in immunology is whether antigen recognition and Fc receptor (FcR)
      binding are allosterically linked. This question is also relevant for therapeutic
      antibody design. Antibody Fab and Fc domains are connected by flexible
      unstructured hinge region. Fc chains have conserved glycosylation sites at
      Asn297, with each conjugated to a core heptasaccharide and forming biantennary Fc
      glycan. The glycans modulate the Fc conformations and functions. It is well known
      that the antibody Fab and Fc domains and glycan affect antibody activity, but
      whether these elements act independently or synergistically is still uncertain.
      We simulated four antibody complexes: free antibody, antigen-bound antibody, FcR
      bound antibody, and an antigen-antibody-FcR complex. We found that, in the
      antibody's "T/Y" conformation, the glycans, and the Fc domain all respond to
      antigen binding, with the antibody population shifting to two dominant clusters,
      both with the Fc-receptor binding site open. The simulations reveal that the Fc
      glycan-receptor complexes also segregate into two conformational clusters, one
      corresponding to the antigen-free antibody-FcR baseline binding, and the other
      with an antigen-enhanced antibody-FcR interaction. Our study confirmed allosteric
      communications in antibody-antigen recognition and following FcR activation. Even
      though we observed allosteric communications through the IgG domains, the most
      important mechanism that we observed is the communication via population shift,
      stimulated by antigen binding and propagating to influence FcR recognition.

PMID- 30212264
TI  - Fibromyalgia: is it a neuropathic pain?
AB  - Fibromyalgia is a chronic pain syndrome of unclear pathophysiology. It is
      believed to be a dysfunction of the CNS, but no definite structural lesion has
      been identified so far. Despite a number of changes in the diagnostic criteria,
      diagnosis remains a clinical one. Since the 2011 revision of the IASP definition
      of neuropathic pain, fibromyalgia has been excluded from the diagnosis of
      neuropathic pain. More recent studies however found newer evidences of
      pathophysiology including small fiber neuropathy in patients with fibromyalgia.
      This may challenge the existing consensus and have implications on future
      diagnosis and management of this condition.

PMID- 30212265
TI  - Immuno-analytical approach and its application for cardiac disease marker
      detection.
AB  - Cardiac troponin-I is a promising diagnostic marker for cardiovascular diseases.
      Troponin-I immunoassays rely on monoclonal antibodies, while polyclonal
      antibodies, cheaper to manufacture, are uncommonly used. The current study
      established an immuno-analytical assay using a polyclonal antibody capable of
      mapping troponin-I antigenic determinant. Proteolytic digestion of troponin-I was
      performed. Antigenic determinant was assigned by separation of fragments using
      gel electrophoresis followed by Western blot and high-performance liquid
      chromatography followed by dot blot. The antigenic determinant region appeared
      within amino acid sequence 30-90. This robust procedure is suitable for early
      prognosis of diseases, stratification of patients, and possibly individualized
      therapy.

PMID- 30212266
TI  - The Role of Elastography in Diagnosis and Staging of Breast Cancer-Related
      Lymphedema.
AB  - BACKGROUND: Early detection of lymphedema gives an opportunity for effective and
      successful treatment of lymphedema. However, the current diagnosis methods,
      except the bioimpedance analysis, perometry, and indocyanine green lymphography,
      have limitations in detecting early stage lymphedema. Sonoelastography is a
      diagnostic ultrasound technique that provides an opportunity to estimate soft
      tissue stiffness. Shear wave elastography (SWE) is a brand new elastography
      technique. Unlike strain elastography, this method is conducted automatically,
      that is, independently of user's manual tissue compression. The aim of this study
      is to establish the role of sonoelastography in diagnosis and staging of
      lymphedema by using the SWE technique in lymphedema patients. METHODS AND
      RESULTS: A total of 36 female lymphedema patients were included in the study.
      There was no significant difference between patients with stages 1 (n = 17) and 2
      (n = 19) lymphedema in terms of age, duration after surgery, and body mass index
      (p > 0.05). But, differences in terms of circumference measurements for forearm
      and arm, L-DEX values, and duration of lymphedema were found to be statistically
      significant (p = 0.002-0.000-0.000-0.001). Elastography measurements between
      normal forearm and forearm with lymphedema showed a statistically significant
      difference (p = 0.012). Correlation was found between circumference measurements
      and elastography values of forearms (p = 0.004, r = 0.471) and L-DEX scores and
      elastography measurements (p = 0.041, r = 0.352). When circumferential
      measurements of the forearms with lymphedema were compared with those with normal
      forearms, stage 1 patients showed no significant difference (p = 0.850), whereas
      a significant difference was detected in stage 2 patients (p = 0.003).
      CONCLUSION: SWE should be a useful tool in diagnosis and distinguishing early and
      late stages of lymphedema.

PMID- 30212267
TI  - Interstitial Cystitis: An Update on the Disease Process and Treatment.
AB  - Interstitial cystitis (IC) is a chronic pain disorder of the bladder that is
      often underdiagnosed and mistreated. The difficulties in diagnosis stem from
      numerous theories regarding pathophysiology and etiology, including the breakdown
      of the glycosaminoglycan (GAG) layer, altered permeability of the urothelium,
      uroinflammation, and neural up-regulation. Dysfunction of the bladder increases
      the struggle for proper treatment and continues to prove difficult for health
      care providers to correctly diagnose and manage IC. If diagnosed and/or managed
      inappropriately, IC may contribute to increased symptom burden and decreased
      quality of life with respect to activities of daily living. When evaluating a
      patient's clinical presentation in combination with predefined risk factors, a
      health care provider can better establish a true diagnosis of IC, which, in turn,
      leads to better management of IC-associated symptoms. This review will help
      health care providers better understand the disease process by discussing
      pathophysiology, pain pathways, and common symptoms of IC, with the goal of
      better aiding them in the proper diagnosis and treatment of patients with IC.

PMID- 30212268
TI  - Real-World Comparative Effectiveness, Safety, and Health Care Costs of Oral
      Anticoagulants in Nonvalvular Atrial Fibrillation Patients in the U.S. Department
      of Defense Population.
AB  - BACKGROUND: The ARISTOTLE trial demonstrated that apixaban had significantly
      lower rates of stroke/systemic embolism (SE) and major bleeding than warfarin;
      however, no direct clinical trials between apixaban and other direct oral
      anticoagulants (DOACs) are available. Few real-world studies comparing the
      effectiveness and safety between DOACs have been conducted. OBJECTIVE: To compare
      effectiveness, safety, and health care costs among oral anticoagulants (OACs) for
      nonvalvular atrial fibrillation (NVAF) patients in the U.S. Department of Defense
      (DoD) population. METHODS: Adult NVAF patients initiating warfarin or DOACs
      (apixaban, rivaroxaban, and dabigatran) were selected from U.S. DoD data from
      January 1, 2013, to September 30, 2015. The first OAC claim date was designated
      as the index date. Patients initiating another OAC were matched 1:1 to apixaban
      patients using propensity score matching to balance demographics and clinical
      characteristics. Cox proportional hazards models were used to estimate the risk
      of stroke/SE and major bleeding for each OAC versus apixaban. Generalized linear
      and two-part models with bootstrapping were used to compare all-cause health care
      costs and stroke/SE-related and major bleeding-related medical costs. RESULTS: Of
      the 41,001 eligible patients, 7,607 warfarin-apixaban, 4,129 dabigatran-apixaban,
      and 11,284 rivaroxaban-apixaban pairs were matched. Warfarin (HR = 1.84; 95% CI =
      1.30-2.59; P < 0.001) and rivar-oxaban (HR = 1.46; 95% CI = 1.08-1.98; P = 0.015)
      were associated with a significantly higher risk of stroke/SE compared with
      apixaban. Dabigatran (HR = 1.17; 95% CI = 0.68-2.03; P = 0.573) was associated
      with a numerically higher risk of stroke/SE compared with apixaban. Warfarin (HR
      = 1.53; 95% CI = 1.24-1.89; P < 0.001), dabigatran (HR = 1.76; 95% CI = 1.27
      2.43; P < 0.001), and rivaroxaban (HR = 1.59; 95% CI = 1.34-1.89; P < 0.001) were
      associated with higher risks of major bleeding compared with apixaban. Compared
      with apixaban, patients prescribed warfarin incurred numerically higher all-cause
      total health care costs per patient per month (PPPM) ($2,498 vs. $2,277; P =
      0.148) and significantly higher stroke/SE-related ($118 vs. $46; P = 0.012) and
      major bleeding-related ($166 vs. $76; P = 0.003) medical costs. Dabigatran
      patients incurred numerically higher all-cause total health care PPPM costs
      ($2,372 vs. $2,143; P = 0.150) and stroke/SE-related medical costs ($61 vs. $32;
      P = 0.240) but significantly higher major bleeding-related costs ($114 vs. $58; P
      = 0.025). Rivaroxaban patients incurred significantly higher all-cause total
      health care costs ($2,546 vs. $2,200; P < 0.001) and major bleeding-related
      medical costs PPPM ($137 vs. $69; P < 0.001) but numerically higher stroke/SE
      related medical costs PPPM ($58 vs. $38; P = 0.057). CONCLUSIONS: Among NVAF
      patients in the U.S. DoD population, warfarin and rivaroxaban were associated
      with a significantly higher risk of stroke/SE and major bleeding compared with
      apixaban. Dabigatran use was associated with a numerically higher risk of
      stroke/SE and a significantly higher risk of major bleeding compared with
      apixaban. Warfarin and dabigatran incurred numerically higher all-cause total
      health care costs compared with apixaban. Rivaroxaban was associated with
      significantly higher all-cause total health care costs compared with apixaban.
      DISCLOSURES This study was funded by Bristol-Myers Squibb and Pfizer, which were
      involved in the study design, as well as in the writing and revision of the
      manuscript. Keshishian and Zhang are paid employees of STATinMED Research, which
      was paid by Bristol-Myers Squibb and Pfizer to conduct this study and develop the
      manuscript. Gupta, Rosenblatt, Hede, and Nadkarni are paid employees of Bristol
      Myers Squibb. Trocio, Dina, Mardekian, Liu, and Shank are paid employees of
      Pfizer.

PMID- 30212269
TI  - Antibodies against human parvovirus B19 in pregnant women in Ogbomoso, Oyo State
      Nigeria.
AB  - Infection caused by Human parvovirus B19 (HPVB19) during pregnancy has been
      associated with adverse effects on fetus such as intrauterine fetal death but
      there is dearth information about the seroprevalence and risk factors among
      pregnant women. This study was carried out to determine the incidence of specific
      IgM antibodies to HPVB19 among pregnant women attending Bowen University Teaching
      Hospital, Ogbomoso, Oyo State. A total of 185 participants, in the age range 18
      49 years, who consented voluntarily after thorough explanation of the purpose of
      the study were recruited for the study. Specific IgM antibodies were detected
      using commercially available third-generation ELISA kits. Data on socio
      demographic characteristics and potential risk factors were collected using
      structured questionnaires. Chi-square (chi2) test was utilized to assess the
      association between the socio-demographic variables and HPVB19 status (P ? 0.05).
      Logistic regression was done to determine the strength of association between the
      potential risk factors and HPVB19 status (P ? 0.05). The overall incidence of IgM
      antibody recorded was 2.70% (5/185). Pregnant women in the age group 36-45 (7.7%)
      years had the highest record. None of the socio-demographic characteristics and
      risk factor considered were significantly associated with acquiring HPVB19.
      However, a one-fold risk was observed among those who had previous history of
      blood transfusion (95% CI = 0.949-0.997, OR = 1.0) The findings in this study
      confirmed the presence of antibodies to HPVB19 among pregnant women in Ogbomoso.
      Public awareness, enlightenment, and screening for the virus should be encouraged
      to prevent fetal complications during pregnancy.

PMID- 30212270
TI  - Soluble glycoproteins of the lacrimal sac: role in defense with special reference
      to prolactin-inducible protein (PIP).
AB  - PURPOSE: Glycoproteins play an important role in human mucosal defenses and
      immunity-related cell-to-cell interactions. The aim of the present study is to
      investigate the presence and patterns of lacrimal sac glycoproteins involved in
      defense mechanisms with a special reference to prolactin-inducible protein (PIP).
      METHODS: The study was performed on healthy lacrimal sacs obtained from
      exenteration samples immediately after surgery and frozen at -80 degrees for
      subsequent analysis. Four lectins namely Concanavalin A (Con A), Dolichos lablab
      lectin (DLL), Wheat Germ agglutinin (WGA), and Momordica charantia lectin (MCL)
      were purified by affinity chromatography. Soluble proteins extract of the
      lacrimal sac was subjected to chromatography on lectin-affigel columns. Eluted
      samples from each of the lectin coupled-affigels were analyzed by 10% SDS-PAGE
      under reducing conditions and the protein bands were visualized using Coomassie
      blue stain. The protein gel bands were further subjected to mass spectrometry for
      glycoprotein analysis. RESULTS: Mass spectrometry identified several
      glycoproteins from the lacrimal sac extracts, with known roles in defense
      mechanisms. The number of such glycoproteins identified were 9 each from Con A
      and DLL-I affinity eluted gel bands and 8 and 14 from MCL and WGA affinity eluted
      gel bands, respectively. Interestingly, PIP was detected in significant
      proportions in all the eluted gel bands with WGA showing the highest expression.
      CONCLUSIONS: This study is the first step towards the lacrimal sac glycoprotein
      profiling. PIP could be a major lead for further work on the etiopathogenesis of
      lacrimal drainage obstructions.

PMID- 30212271
TI  - Regulating stool for microbiota transplantation.
AB  - In 2017 Gut Microbes published "A proposed definition of microbiota
      transplantation for regulatory purposes," in which the authors suggest that
      regulators should draw a line between microbiota transplants and biologic drugs
      composed of microbial communities (or other products derived from the human
      microbiome). They develop a definition of microbiota transplantation (MT) to help
      regulators draw such a line, and suggest that MT need not be, and cannot be,
      regulated as a biologic drug (a live biotherapeutic product). However, an
      agency's regulatory scrutiny of a medical product should be commensurate with
      that product's degree of risk to patients. Products for MT, such as stool, are
      likely to be as or more dangerous than more highly manipulated microbial products
      that scientists and regulators agree should be regulated as biologic drugs.
      Therefore, we argue that MT, as defined by the authors, should receive the same
      regulatory oversight as any other biologic product intended to cure, mitigate,
      treat, or prevent disease. We also suggest that regulators might not be able to
      operationalize the proposed definition of MT.

PMID- 30212272
TI  - Caries Diagnosis in Dental Practices: Results From Dentists in a Brazilian
      Community.
AB  - The aim of this study was to assess practices related to diagnosis of dental
      caries among dentists (n=217) from Araraquara, Sao Paulo State, Brazil. Data on
      sociodemographic information and practitioner characteristics were collected
      using a pretested questionnaire, and data on practices related to caries
      diagnosis were gathered by using a translated and culturally adapted
      questionnaire from the US National Dental Practice-Based Research Network.
      Descriptive statistics and regression analyses were used for data analysis.
      Respondents reported using in most of their patients radiographs (Rx) to diagnose
      proximal caries (59%), explorer (Ex) for the diagnosis of occlusal caries (64%)
      and on the margins of existing restorations (79%), as well as air jet (AJ) with
      drying (92%). Magnification (M) (25%), fiber optic transillumination (FOTI; 14%),
      and laser fluorescence (LF) (3%) were used in the minority of patients.
      Regression analysis revealed that the following dentists' characteristics were
      significantly associated (p<0.05) with the use of diagnostic methods on a greater
      percentage of their patients: advanced degree (Rx, FOTI), higher percentage of
      patients with individualized caries prevention (Rx, FOTI, M), more years since
      dental school graduation (Ex, M), and work in an exclusively private practice
      model (LF). In conclusion, most Brazilian dentists from Araraquara reported they
      most commonly use visual, tactile, and radiographic imaging for the diagnosis of
      dental caries. Some dentists' characteristics, such as time from dental school
      graduation and having a postgraduation course, were associated with the use of
      certain diagnostic methods.

PMID- 30212273
TI  - Effect of Different Adhesive Strategies and Time on Microtensile Bond Strength of
      a CAD/CAM Composite to Dentin.
AB  - PURPOSE: The aim of this study was to evaluate the effect of adhesive strategy
      and time on the microtensile bond strength of a computer-aided design/computer
      aided manufacturing (CAD/CAM) composite to dentin. METHODS AND MATERIALS: Sixty
      CAD/CAM composite blocks were bonded to human dentin with simplified bonding
      agents using etch-and-rinse and self-etching approaches and amine-based and amine
      free resin cements, with and without the application of a dual-cure activator
      (DCA; n=10): SBP-ARC (Adper Single Bond Plus + RelyX ARC), SBP-RXU (Adper Single
      Bond Plus + RelyX Ultimate), SBP-DCA-RXU (Adper Single Bond Plus + DCA + RelyX
      Ultimate), SBU-ARC (Scotchbond Universal + RelyX ARC), SBU-RXU (Scotchbond
      Universal + RelyX Ultimate), and SBU-DCA-ARC (Scotchbond Universal + DCA + RelyX
      ARC). Each specimen was light cured for 40 seconds under load and stored in
      distilled water at 37 degrees C for seven days. Stick-shaped specimens (1.0 mm2)
      were obtained. Half of the specimens underwent microtensile bond strength
      testing, and the other half were subjected to the same tests after six months of
      storage. Failure mode was determined using an optical microscope (40*). The data
      were analyzed by a two-way analysis of variance followed by the Games-Howell test
      and Student t-test (preset alpha of 0.05). RESULTS: After seven days, SBU-RXU
      presented the highest mean bond strength, statistically different from only SBU
      ARC ( p<0.05). Most of the groups exhibited a statistically significant reduction
      in bond strength after 6 months ( p<0.05), except SBP-RXU and SBU-ARC ( p>0.05).
      CONCLUSION: The adhesive strategy, with different associations between adhesive
      systems and resin cements, as well as the use of a DCA, affected the bond
      strength of both amine-free and amine-based resin cements to a CAD/CAM composite.

PMID- 30212274
TI  - Diverse Plasmids Harboring blaCTX-M-15 in Klebsiella pneumoniae ST11 Isolates
      from Several Asian Countries.
AB  - To reveal whether an increase of CTX-M-15-producing Klebsiella pneumoniae ST11
      isolates is due to clonal dissemination across the countries, plasmids (pHK02
      026, pM16-13, pIN03-01, and pTH02-34) were extracted from four K. pneumoniae
      isolates collected in Hong Kong, Malaysia, Thailand, and Indonesia, respectively.
      Complete sequencing of blaCTX-M-15-carrying plasmids was performed. In addition
      to the four plasmids, a previously sequenced plasmid (pKP12226) of a K.
      pneumoniae ST11 isolate from Korea was included in the analysis. While pIN03-01
      and pTH02-34, which belonged to the incompatibility group IncX3, showed nearly
      the same structure, the others of IncF1A or IncFII exhibited very different
      structures. The number and kinds of antibiotic genes found in the plasmids were
      also different from each other. Cryptic prophage genes were identified in all
      five blaCTX-M-15-harboring plasmids from the ST11 isolates; P1-like region in
      pKP12226, CPZ-55 prophage region in pHK02-026, phage shock operon pspFABCD in
      pM16-13, and SPBc2 prophage yokD in pIN03-01 and pTH02-34. The plasmids with
      blaCTX-M-15 in the prevailing K. pneumoniae ST11 isolates in Asian countries
      might emerge from diverse origins by recombination. The prevalence of CTX-M-15
      producing K. pneumoniae ST11 clone in Asian countries is not mainly due to the
      dissemination of a single strain.

PMID- 30212275
TI  - Outcome of isolated posterior cruciate ligament reconstruction at mean 6.3-year
      follow up: a consecutive case series.
AB  - OBJECTIVES: There is a paucity of reporting on surgical outcomes of isolated
      posterior cruciate ligament reconstruction (PCLR). We hypothesize that isolated
      PCL injuries failing nonoperative treatment achieve good outcomes and are able to
      return to sport following PCLR. METHODS: A retrospective analysis was performed
      to identify patients with isolated PCL injuries that underwent reconstruction
      between 2001 and 2014. Patients with multi-ligamentous injury or another
      concomitant knee pathology were excluded. Medical records were reviewed for
      demographic, clinical and operative data. Patients were contacted for
      administration of a telephone-based questionnaire which included the
      International Knee Documentation Committee (IKDC) Subjective Knee Evaluation
      form, Lysholm-Tegner scales, Marx activity scale (MAS), return to sport status,
      and patient satisfaction instruments. RESULTS: A total of 15 isolated PCL
      reconstructions in 14 patients with a mean age of 27.5 years (range 17-43) met
      the study inclusion criteria; mean follow up was 6.3 years (range 1.4-15.2). Pre
      operatively, the primary complaint was knee instability in all patients; on
      physical examination, lack of a firm end point during posterior drawer testing
      was found in 93% (14/15) of the knees. In total, 12 of 15 knees underwent
      transtibial, single-bundle PCLR and three of 15 underwent tibial inlay, double
      bundle PCLR. Graft types included: quadriceps autograft (7/15), Achilles
      allograft (6/15), and hamstring autograft (2/15). There were no graft failures in
      our patient cohort. At most recent follow up the mean scores respectively on the
      IKDC form, Lysholm-Tegner scales and MAS were (standard deviation): 77.3 (16.5),
      83.1 (17.9), 6.13 (2.6), and 7.1 (6.0). All fourteen patients were athletes prior
      to their injury and 79% (11/14) returned to sport and overall patient
      satisfaction was 9.2/10. CONCLUSIONS: Isolated PCLR provides good outcomes at
      mean medium-term follow up with restoration of function, high rate of return to
      sport and overall patient satisfaction.

PMID- 30212276
TI  - Pharmacodynamic safety of clopidogrel monotherapy in patients under oral
      anticoagulation with a vitamin K antagonist undergoing coronary stent
      implantation.
AB  - Current guidelines recommend as treatment option in patients on oral
      anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) an
      antiplatelet monotherapy with clopidogrel if there is an increased risk for
      bleeding. However, retrospective data suggested a potential interaction of
      clopidogrel and the vitamin K antagonist (VKA) phenprocoumon leading to a
      diminished antiplatelet effect. This would increase the ischemic risk of patients
      treated with this combination. Thus, this prospective study sought to evaluate
      the pharmacodynamic effect of clopidogrel monotherapy in patients on
      phenprocoumon undergoing PCI and assessed clinical outcomes. This study enrolled
      100 patients on aspirin plus clopidogrel (DAPT-cohort, without indication for
      VKA) and 100 patients on clopidogrel monotherapy plus phenprocoumon (OAC-cohort)
      undergoing elective PCI. Platelet reactivity was assessed by impedance
      aggregometry on day 1 following PCI. Ischemic (death, stroke, or myocardial
      infarction) and bleeding (BARC 2-5) events within 12 months were compared in a
      propensity score adjusted model. Platelet reactivity was not different in the OAC
      and DAPT-cohort (187 [127-242] vs. 167 [126-218] AU*min; p = 0.23). Overall, 17
      ischemic and 34 bleeding events were recorded during follow-up. The OAC-cohort
      showed a nonsignificant trend to an 80% higher incidence for ischemic and
      bleeding events in unadjusted analyses, which disappeared following adjustment
      (ischemic events HR 1.07, 95%-CI 0.32-3.59, p = 0.91; bleeding events HR 1.25,
      95%-CI 0.46-3.40, p = 0.67). Following PCI, the pharmacodynamic effect of a
      clopidogrel monotherapy together with phenprocoumon is similar as compared to
      DAPT without a VKA, and not associated with an increased risk for ischemic events
      beyond the higher underlying baseline risk.

PMID- 30212277
TI  - An updated understanding of the mechanisms involved in chemotherapy-induced
      neuropathy.
AB  - The burdensome condition of chemotherapy-induced peripheral neuropathy occurs
      with various chemotherapeutics, including bortezomib, oxaliplatin, paclitaxel and
      vincristine. The symptoms, which include pain, numbness, tingling and loss of
      motor function, can result in therapy titrations that compromise therapy
      efficacy. Understanding the mechanisms of chemotherapy-induced peripheral
      neuropathy is therefore essential, yet incompletely understood. The literature
      presented here will address a multitude of molecular and cellular mechanisms,
      beginning with the most well-understood cellular and molecular-level changes.
      These modifications include alterations in voltage-gated ion channels,
      neurochemical transmission, organelle function and intracellular pathways. System
      level alterations, including changes to glial cells and cytokine activation are
      also explored. Finally, we present research on the current understanding of
      genetic contributions to this condition. Suggestions for future research are
      provided.

PMID- 30212278
TI  - Long-Term Outcomes and Complications of Baerveldt Glaucoma Drainage Implants in
      Adults with Glaucoma Secondary to Uveitis.
AB  - PURPOSE: This study investigated the efficacy and safety of Baerveldt glaucoma
      implants (BGI) in adults with uveitic glaucoma (UG) at the Manchester Uveitis
      Clinic. METHODS: This was a retrospective study of 42 patients with UG who
      underwent BGI implantation between 2006 and 2015. Primary outcome measures were
      intraocular pressure (IOP) reduction and number of medications at 5-year follow
      up. Three IOP success criteria were chosen: 1.IOP <=21 mmHg and >=20% reduction
      from baseline 2.IOP <=17 mmHg and >=20% reduction from baseline and 3.IOP <=14
      mmHg. RESULTS: The mean pre-operative IOP was 29.5 +/- 9.5 mmHg on 3.9
      antiglaucoma drops. At 5-year follow-up, IOP reduced to 14.4 +/- 7.0 mmHg (p <
      0.005) on 1.4 drops. The cumulative probability of failure at 5 years based on
      criteria 1, 2, and 3 was 24.3%, 39.6%, and 56.3%, respectively. CONCLUSION: This
      study demonstrated that BGI are safe and effective in refractory UG, especially
      in younger adults with complex uveitis.

PMID- 30212280
TI  - Telelactation Via Mobile App: Perspectives of Rural Mothers, Their Care
      Providers, and Lactation Consultants.
AB  - BACKGROUND: Rural-urban disparities exist in breastfeeding rates and availability
      of lactation support. Direct-to-consumer (DTC) telelactation that uses two-way
      video through personal devices has the potential to increase access to
      international board-certified lactation consultants (IBCLCs) in rural settings
      that lack them. This study describes the feasibility and acceptability of DTC
      telelactation for rural mothers. METHODS: We conducted semi-structured interviews
      among various stakeholders involved in a study exploring the impact of
      telelactation through mobile phone app in rural Pennsylvania. Interviewees
      included mother participants assigned to receive telelactation (n = 17), IBCLCs
      employed by the telelactation vendor (n = 7), and nurses (n = 2) and physicians
      (n = 1) caring for mother participants at the recruitment hospital. Thematic
      content analysis was used to analyze qualitative data. RESULTS: Interviewees
      reported that telelactation was convenient and efficient, provided a needed
      service in rural areas lacking breastfeeding support services, and increased
      maternal breastfeeding confidence. Telelactation was noted to have several
      advantages over in-person and telephone-based support. Barriers to use included
      maternal reluctance to conduct video calls with an unknown provider, preference
      for community-based breastfeeding resources, and technical issues including
      limited WiFi in rural areas. CONCLUSIONS: Among rural women who experience
      inequitable access to qualified breastfeeding support resources, DTC
      telelactation appears to be an acceptable delivery model for lactation
      assistance.

PMID- 30212281
TI  - The Empower Nudge lottery to increase dual protection use: a proof-of-concept
      randomised pilot trial in South Africa.
AB  - The objective of this study is to measure the preliminary efficacy of a pilot
      intervention, grounded in behavioural economics, increasing adherence of dual
      protection (simultaneous use of effective modern contraception and a barrier
      method, such as a condom) to protect against HIV, other sexually transmitted
      infections, and unintended pregnancy. Between 2015 and 2016, 100 women aged 18-40
      years, seeking post-abortion care in Cape Town, South Africa were recruited to
      Empower Nudge, a randomised controlled trial to test a lottery incentive
      intervention designed to increase dual protection. At baseline, the mean age of
      participants was 27 years; 82% of them were from South Africa; 58% self
      identified as Black African; average education completed was 11.7 years. At three
      months, assignment to the lottery intervention was associated with higher odds of
      returning for study visits (OR: 6.0; 95%CI: 2.45 to 14.7, p < 0.01), higher
      condom use (OR: 4.5; 95%CI: 1.43 to 14.1; p < 0.05), and higher use of dual
      protection (OR: 3.16; 95%CI: 1.01 to 9.9; p < 0.05). Only 60% of the study
      population returned after three months and only 38% returned after six months.
      Women who receive post-abortion care represent a neglected population with an
      urgent need for HIV and pregnancy prevention. Dual protection is a critically
      important strategy for this population. Lottery-based behavioural economics
      strategies may offer possible ways to increase dual protection use in this
      population. Further research with larger samples, longer exposure time, and more
      sites is needed to establish fully powered efficacy of lottery incentives for
      dual protection; using objective verification for monitoring.

PMID- 30212282
TI  - Multi-disciplinary approach to perioperative risk assessment and post-transplant
      management for liver transplantation in a patient at risk for Brugada syndrome.
AB  - Brugada syndrome, an autosomal dominant genetic disorder, is characterised by
      abnormal electrocardiogram findings and increased risk of ventricular
      tachyarrhythmias and sudden cardiac death. Our report describes the multi
      disciplinary perioperative management of a 28-year-old patient presenting to the
      Duke Transplant Center with a familial sodium channel gene SCN51 mutation
      concerning Brugada syndrome. We discuss the preparatory work-up, medication
      review and appropriate post-surgical follow-up for patients undergoing liver
      transplant surgery with cardiac monitoring.

PMID- 30212283
TI  - Required time for setting up an anaesthesia machine mounted on a movable ceiling
      pendant.
AB  - The present study was performed to evaluate the duration of time required to set
      up an anaesthesia machine mounted on an automated or manually movable ceiling
      pendant. Nurses moved the machine's position according to the surgical site
      (right or left). The duration of time required to set up the anaesthesia machine
      for surgery was compared between automated and manual operation and among nurses
      with varying years of work experience. Movement of the anaesthesia machine from
      the right to left position took longer for the automated (278 +/- 11s) than
      manual (188 +/- 63s) method. However, no difference was observed between
      automated (288 +/- 11s) and manual (267 +/- 140s) movement of the machine from
      the left to right position. Experienced nurses took less time in both directions.
      Manual movement took less time than automated movement in the right-to-left
      direction, which may be advantageous when nurses are in a hurry or have
      musculoskeletal system disorders and may allow them to perform other operating
      room preparation tasks. Either automated or manual movement may be used depending
      on the situation. Both the larger deviations with manual movement and the shorter
      time required by experienced nurses suggest that training and experience shorten
      the manual set-up time.

PMID- 30212284
TI  - A review of Operating Department Practitioner students' experiences of clinical
      placements as a result of changing organisations in each academic year.
AB  - Operating Department Practitioner students as part of their education undertake
      placements that enable them alongside their academic studies to meet the Health
      and Care Professions Council Standards of Proficiency; however, like all
      education providers there was an annual shortage of appropriate placements. As a
      result, the organisation involved in this review needed to explore an alternative
      approach to allocating clinical placements. In addition, the course team wanted
      to change how students gained their clinical skills and possibly increase their
      understanding of the Operating Department Practitioner role. Traditionally the
      institution involved like other Operating Department Practitioner education
      providers placed students in one organisation for all of their clinical
      placements unlike other professions such as nursing who placed students in
      different areas. The review resulted in students being placed in a different
      organisation in each year of their course. A qualitative methodology in the form
      of focus groups was employed to review students' views of the change and their
      clinical experiences and this resulted in students highlighting area such as
      readiness for being qualified and links to evidenced-based practice as benefits
      of the new system. The review has been successful in terms of placement numbers
      but also student experiences, although an ongoing review is being undertaken, the
      change has been successful.

PMID- 30212285
TI  - Getting in the Flo: My year as a scholar.
AB  - In November 2016, I was awarded an Emerging Leaders Scholarship from the Florence
      Nightingale Foundation to help me positively impact patient care and also improve
      how I lead change within my organisation. This article highlights some of the
      learning experiences over the last year and the impact that the Scholarship has
      had.

PMID- 30212286
TI  - The story of minimal access surgery.

PMID- 30212287
TI  - Care of the person with a learning disability in the perioperative environment.

PMID- 30212288
TI  - An evidence-based review of enhanced recovery after surgery in total knee
      replacement surgery.
AB  - RATIONALE: Enhanced recovery after surgery is gaining popularity among
      orthopaedic surgeons across the globe and hence a strong evidence base had to be
      reviewed to make an evidence-based sustainable protocol. Methods The following
      databases, PubMed, OVID, Cochrane database and EMBASE were searched. The search
      was limited to 15 components of enhanced recovery after surgery programme which
      is divided into preoperative, intraoperative and postoperative phases. Inclusion
      criteria were restricted to articles published in English within the last 15
      years and articles comprising of unicompartmental arthroplasty, revision knee
      arthroplasty, bilateral simultaneous knee arthroplasty and only hip arthroplasty
      excluded. The full texts were analysed and controversies and limitations of
      various studies were summarised. Discussion Each component of the programme was
      thoroughly reviewed and strength and weaknesses of the evidence base summarised.
      The strength of the evidence was assessed by critically appraising the study
      methodology and justifying the appropriateness of the inclusion in enhanced
      recovery after surgery protocol. Conclusion Enhanced recovery after surgery has
      already been used successfully in various surgical specialities. Enhanced
      recovery after surgery programmes in knee arthroplasty are yet to be established
      as a universal practice to be adopted globally. This evidence-based review
      provides an insight into the best evidence linked to each component and their
      rationale for inclusion in the proposed enhanced recovery after surgery protocol.

PMID- 30212289
TI  - Special Issue: Stem Cells, Radiation, and Microgravity.

PMID- 30212290
TI  - Reply to A.J. Chang et al and A. Gomez-Iturriaga et al.

PMID- 30212291
TI  - Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Relapsed or
      Refractory Pediatric B-Cell Acute Lymphoblastic Leukemia.
AB  - Purpose The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel
      was recently approved to treat relapsed or refractory pediatric acute
      lymphoblastic leukemia. With a one-time infusion cost of $475,000,
      tisagenlecleucel is currently the most expensive oncologic therapy. We aimed to
      determine whether tisagenlecleucel is cost effective compared with currently
      available treatments. Methods Markov modeling was used to evaluate
      tisagenlecleucel in pediatric relapsed or refractory acute lymphoblastic leukemia
      from a US health payer perspective over a lifetime horizon. The model was
      informed by recent multicenter, single-arm clinical trials. Tisagenlecleucel
      (under a range of plausible long-term effectiveness) was compared with
      blinatumomab, clofarabine combination therapy (clofarabine, etoposide, and
      cyclophosphamide), and clofarabine monotherapy. Scenario and probabilistic
      sensitivity analyses were used to explore uncertainty. Main outcomes were life
      years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs),
      and incremental cost-effectiveness ratio (3% discount rate). Results With an
      assumption of a 40% 5-year relapse-free survival rate, tisagenlecleucel increased
      life expectancies by 12.1 years and cost $61,000/QALY gained. However, at a 20% 5
      year relapse-free survival rate, life-expectancies were more modest (3.8 years)
      and expensive ($151,000/QALY gained). At a 0% 5-year relapse-free survival rate
      and with use as a bridge to transplant, tisagenlecleucel increased life
      expectancies by 5.7 years and cost $184,000/QALY gained. Reduction of the price
      of tisagenlecleucel to $200,000 or $350,000 would allow it to meet a
      $100,000/QALY or $150,000/QALY willingness-to-pay threshold in all scenarios.
      Conclusion The long-term effectiveness of tisagenlecleucel is a critical but
      uncertain determinant of its cost effectiveness. At its current price,
      tisagenlecleucel represents reasonable value if it can keep a substantial
      fraction of patients in remission without transplantation; however, if all
      patients ultimately require a transplantation to remain in remission, it will not
      be cost effective at generally accepted thresholds. Price reductions would
      favorably influence cost effectiveness even if long-term clinical outcomes are
      modest.

PMID- 30212292
TI  - Treating Patients With Bladder Cancer: Is There an Ethical Obligation to Include
      Smoking Cessation Counseling?

PMID- 30212293
TI  - Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases.

PMID- 30212294
TI  - Should I Have Lied?

PMID- 30212295
TI  - National Cancer Institute Breast Cancer Steering Committee Working Group Report
      on Meaningful and Appropriate End Points for Clinical Trials in Metastatic Breast
      Cancer.
AB  - Purpose To provide evidence-based consensus recommendations on choice of end
      points for clinical trials in metastatic breast cancer, with a focus on biologic
      subtype and line of therapy. Methods The National Cancer Institute Breast Cancer
      Steering Committee convened a working group of breast medical oncologists,
      patient advocates, biostatisticians, and liaisons from the Food and Drug
      Administration to conduct a detailed curated systematic review of the literature,
      including original reports, reviews, and meta-analyses, to determine the current
      landscape of therapeutic options, recent clinical trial data, and natural history
      of four biologic subtypes of breast cancer. Ongoing clinical trials for
      metastatic breast cancer in each subtype also were reviewed from
      ClinicalTrials.gov for planned primary end points. External input was obtained
      from the pharmaceutic/biotechnology industry, real-world clinical data
      specialists, experts in quality of life and patient-reported outcomes, and
      combined metrics for assessing magnitude of clinical benefit. Results The
      literature search yielded 146 publications to inform the recommendations from the
      working group. Conclusion Recommendations for appropriate end points for
      metastatic breast cancer clinical trials focus on biologic subtype and line of
      therapy and the magnitude of absolute and relative gains that would represent
      meaningful clinical benefit.

PMID- 30212296
TI  - Reply to L. Zeng et al.

PMID- 30212297
TI  - Addressing Financial Barriers to Patient Participation in Clinical Trials: ASCO
      Policy Statement.
AB  - Research conducted through clinical trials is essential for evaluating new
      treatment modalities, establishing new standards of cancer care, and ultimately
      improving and prolonging the lives of patients with cancer. However,
      participation in trials has been low, and this is attributable to various factors
      including patient financial barriers. Such financial barriers include the rising
      cost of cancer care; a lack of transparency in coverage policy; and the
      perception of ethical, compliance, or institutional impediments to patient
      financial support. ASCO convened a roundtable discussion with a variety of
      stakeholders to define the scope of the problem, as well as to identify clinical
      practice and policy solutions applicable at the institutional and system-wide
      levels. This statement summarizes key discussions from the ASCO Roundtable, as
      well as findings from the literature, and provides ASCO's recommendations for
      overcoming financial barriers that may otherwise prevent participation in
      clinical trials. These recommendations broadly address the following key areas:
      (1) improving the policy environment for coverage of clinical trials; (2)
      facilitating transparency among providers, patients, and payers for trial-related
      out-of-pocket costs; (3) refuting the specter of inducement to enable targeted
      financial support for patients; and (4) improving the available data on costs of
      cancer clinical trials.

PMID- 30212298
TI  - The American Brachytherapy Society and the American Radium Society Appropriate
      Use Criteria Genitourinary Committee Endorse the American Society of Clinical
      Oncology/Cancer Care Ontario Guidelines.

PMID- 30212299
TI  - Reply to D.M. Green.

PMID- 30212300
TI  - High-Risk Localized Prostate Cancer: How Important Is the Addition of
      Brachytherapy to External-Beam Radiotherapy?

PMID- 30212301
TI  - Should Crizotinib Take It All in ROS1-Positive Non-Small-Cell Lung Cancer?

PMID- 30212302
TI  - Exercise training-induced effects on the abdominal subcutaneous adipose tissue
      phenotype in obese humans.
AB  - BACKGROUND: Rodent studies have indicated that physical exercise may improve
      adipose tissue function. We investigated the effects of a 12-weeks supervised,
      progressive exercise training program on adipocyte morphology and abdominal
      subcutaneous adipose tissue function in metabolically well-phenotyped, obese
      subjects. METHODS: 21 obese men participated in a 12-weeks supervised,
      progressive, combined exercise training program, consisting of aerobic exercise
      (30min at 70% of Wmax, 2x/week) and resistance exercise (3x10 repetitions at 60%
      of 1RM, 1x/week), with adjustment of exercise intensity every 4 weeks. At
      baseline and after intervention, abdominal subcutaneous adipose tissue biopsies
      were collected to determine 1) adipocyte morphology, 2) gene expression of
      markers for lipolysis, inflammation, browning, adipokines and mitochondrial
      biogenesis/function, 3) protein expression of mitochondrial oxidative
      phosphorylation (OXPHOS) complexes and 4) ex vivo basal and beta2-adrenergic
      stimulated lipolysis. RESULTS: The exercise training program, which increased
      maximal aerobic capacity (P<0.001) and muscle strength (P<0.001), slightly
      reduced adipose tissue mass (~ 0.7 kg, P=0.021) but did not affect abdominal
      subcutaneous adipocyte size (P=0.744), adipose tissue gene expression of markers
      for mitochondrial biogenesis and function, browning, lipolysis, inflammation and
      adipokines, total OXPHOS protein content (P=0.789) and beta2-adrenergic
      sensitivity of lipolysis (P=0.555). CONCLUSIONS: A 12-weeks supervised,
      progressive exercise training program did neither alter abdominal subcutaneous
      adipocyte morphology and adipose tissue gene/protein expression of markers
      related to adipose tissue function, nor beta2-adrenergic sensitivity of lipolysis
      in obese male subjects.

PMID- 30212303
TI  - Effect of reflexive activation of motor units on torque development during
      electrically-evoked contractions of the triceps surae muscle.
AB  - The aim of the study was to identify stimulation conditions permitting the
      occurrence of extra-torque (ET) and to examine their impact on spinal and
      corticospinal excitabilities. Twelve subjects received stimulation trains over
      the tibial nerve (20 sec duration, 1ms pulse duration) that were delivered at
      three stimulation frequencies (20, 50 and 100 Hz) and at 5 intensities (110, 120,
      130, 140 and 150% of the motor threshold). Torque-Time Integral (TTI) of each
      stimulation train was calculated. Spinal (Hmax/Mmax) and corticospinal
      (MEPmax/Mmax) excitabilities were assessed at rest before and after each
      stimulation train by tibial nerve stimulation and by transcranial magnetic
      stimulation, respectively. Moreover, a twitch at each stimulation intensity was
      delivered before and after each stimulation train. The EMG associated with this
      twitch was analyzed in order to identify the initial motor unit (MU) recruitment
      pathway before each stimulation train and discriminate trials to H-trials
      (indirect recruitment) and M-trials (direct recruitment). TTI was higher for H
      trials compared to M-trials for all tested frequencies. There was a decrease in
      Hmax/Mmax for the 20 Hz-H trials and an increase for the 100 Hz-H trials, while
      MEPmax/Mmax remained unchanged at post measurements. Present results demonstrate
      that the initial MU recruitment pattern plays a main role in the ET occurrence,
      with the indirect recruitment via the afferent volley being substantial for its
      development. The modulations of Hmax/Mmax without changes in MEPmax/Mmax, suggest
      that the ET development affects spinal excitability and that these changes are
      frequency-dependent.

PMID- 30212304
TI  - The intersection between gonadal function and vascular aging in women.
AB  - Vascular aging, characterized by endothelial dysfunction and large elastic
      arterial stiffening, is a major risk factor for age-associated cardiovascular
      disease (CVD). Although women have a lower prevalence of CVD until mid-life,
      prevalence rates increase rapidly coincident with the menopausal transition to
      match those observed in men. The menopausal transition, or perimenopause, is a
      chaotic period that is associated with increased symptoms (e.g., hot flashes,
      depressed mood, anxiety, sleep disturbances) and CVD risk factors due to changes
      in the hormonal environment. Because these quality of life factors and CVD risk
      factors also change with aging, the arteries of women appear to endure a double
      insult. Our laboratory has been investigating how changes in gonadal function and
      hormone levels with the menopause transition impacts the vascular aging process
      in healthy women. Our work has shown that vascular endothelial function
      progressively declines and large elastic arterial stiffness is greater across the
      stages of the menopausal transition. This acceleration in vascular aging may be
      due to the loss of vasodilatory, antioxidant, anti-inflammatory and anti
      proliferative effects of estradiol on the vascular wall. This mini-review will
      discuss the impact of changes in gonadal function and hormones with the
      menopausal transition on vascular aging in women, and areas for investigations to
      further our understanding of the intersection between gonadal function and
      vascular aging.

PMID- 30212305
TI  - Healthy Lifestyle-Based Approaches for Successful Vascular Aging.
AB  - This review summarizes a presentation given at the 2016 Gerontological Society of
      America Annual Meeting as part of a Vascular Aging Workshop. The development of
      age-related vascular dysfunction increases the risk of cardiovascular disease as
      well as other chronic age-associated disorders, including chronic kidney disease
      and Alzheimer's disease. Healthy lifestyle behaviors, most notably regular
      aerobic exercise and certain dietary patterns, are considered "first-line"
      strategies for the prevention and/or treatment of vascular dysfunction with
      aging. Despite the well-established benefits of these strategies, however, many
      older adults do not meet the recommended guidelines for exercise or consume a
      healthy diet. Therefore, it is important to establish alternative and/or
      complementary evidence-based approaches to prevent or reverse age-related
      vascular dysfunction. Time-efficient forms of exercise training, hormetic
      exposure to mild environmental stress, fasting "mimicking" dietary paradigms, and
      nutraceutical/pharmaceutical approaches to favorably modulate cellular and
      molecular pathways activated by exercise and healthy dietary patterns may hold
      promise as such alternative approaches. Determining the efficacy of these novel
      strategies is important to provide alternatives for adults with low adherence to
      conventional healthy lifestyle practices for healthy vascular aging.

PMID- 30212306
TI  - Protein intake in the early recovery period after exhaustive exercise improves
      performance the following day.
AB  - : The aim of the present study was to investigate the effect of protein and
      carbohydrate ingestion during early recovery from exhaustive exercise on
      performance after 18 h recovery. Eight elite cyclists (VO2max 74.0+/-1.6 ml?kg
      1?min-1) completed two exercise and diet interventions in a double-blinded,
      randomized, crossover design. Participants cycled first at 73% of VO2max (W73%)
      followed by one-min intervals at 90% of VO2max until exhaustion. During the first
      two hours of recovery, participants ingested either 1.2 g carbohydrate?kg-1?h-1
      (CHO) or 0.8 g carbohydrate + 0.4 g protein?kg-1?h-1 (CHO+PROT). The diet during
      the remaining recovery period was similar for both interventions and adjusted to
      body weight. After an 18 h recovery, cycling performance was assessed with a 10 s
      sprint test, 30 min of cycling at W73%, and a cycling time trial (TT). The TT was
      8.5% faster (41:53+/-1:51 min vs 45:26+/-1:32 min; p<0.03) after CHO+PROT
      compared to CHO. Mean power output during the sprints was 3.7% higher in CHO-PROT
      compared to CHO (1063+/-54 W vs 1026+/-53 W; p<0.01). Nitrogen balance in the
      recovery period was negative in CHO and neutral in CHO+PROT (-82.4+/-11.5 vs
      7.0+/-15.4 mg?kg-1; p<0.01). IN CONCLUSION: TT and sprint performances were
      improved 18 h after exhaustive cycling by CHO-PROT supplementation during the
      first two hours of recovery compared with isoenergetic CHO supplementation. Our
      results indicate that intake of carbohydrate plus protein after exhaustive
      endurance exercise more rapidly converts the body from a catabolic to an anabolic
      state than carbohydrate alone, thus speeding recovery and improving subsequent
      cycling performance.

PMID- 30212307
TI  - Microendoscopy reveals positive correlation in multiscale length changes and
      variable sarcomere lengths across different regions of human muscle.
AB  - Sarcomere length is a key physiological parameter that affects muscle force
      output; however, our understanding of the scaling of human muscle from sarcomere
      to whole muscle is based primarily on cadaveric data. The aims of this study were
      to explore the in vivo relationship between passive fascicle length and passive
      sarcomere length at different muscle-tendon unit lengths and determine whether
      sarcomere and fascicle length relationships are the same in different regions of
      muscle. A microendoscopy needle probe capable of in vivo sarcomere imaging was
      inserted into a proximal location of the human tibialis anterior muscle at three
      different ankle positions (5 degrees  dorsiflexion [DF], 5 degrees  plantar
      flexion [PF], 15 degrees  PF) and one distal location at a constant ankle
      position (5 degrees  PF distal). Ultrasound imaging of tibialis anterior
      fascicles, centred on the location of the needle probe, was performed for each
      condition to estimate fascicle length. Sarcomere length and fascicle length
      increased with increasing muscle-tendon unit length, although the correlation
      between sarcomere length change and muscle fascicle length change was only
      moderate (r2 = 0.45). Passive sarcomere length was longer at the distal imaging
      site than the proximal site (P = 0.01). When sarcomere number was estimated from
      sarcomere length and fascicle length, there were fewer sarcomeres in the fibres
      of distal location than the proximal location (P = 0.01). These data demonstrate
      that fascicle length changes are representative of sarcomere length changes,
      although significant variability in sarcomere length exists within a muscle, and
      sarcomere number per fibre is region dependent.

PMID- 30212308
TI  - Measuring mistreatment of women throughout the birthing process: implications for
      quality of care assessments.
AB  - Measuring mistreatment and quality of care during childbirth is important in
      promoting respectful maternity care. We describe these dimensions throughout the
      birthing process from admission, delivery and immediate postpartum care. We
      observed 677 client-provider interactions and conducted 13 facility assessments
      in Kenya. We used descriptive statistics and logistic regression model to
      illustrate how mistreatment and clinical process of care vary through the
      birthing process. During admission, the prevalence of verbal abuse was 18%, lack
      of informed consent 59%, and lack of privacy 67%. Women with higher parity were
      more likely to be verbally abused [AOR: 1.69; (95% CI 1.03,2.77)]. During
      delivery, low levels of verbal and physical abuse were observed, but lack of
      privacy and unhygienic practices were prevalent during delivery and postpartum
      (>65%). Women were less likely to be verbally abused [AOR: 0.88 (95% CI 0.78,
      0.99)] or experience unhygienic practices, [AOR: 0.87 (95% CI 0.78, 0.97)] in
      better-equipped facilities. During admission, providers were observed creating
      rapport (52%), taking medical history (82%), conducting physical assessments
      (5%). Women's likelihood to receive a physical assessment increased with higher
      infrastructural scores during admission [AOR: 2.52; (95% CI 2.03, 3.21)] and
      immediately postpartum [AOR 2.18; (95% CI 1.24, 3.82)]. Night-time deliveries
      were associated with lower likelihood of physical assessment and rapport creation
      [AOR; 0.58; (95% CI 0.41,0.86)]. The variability of mistreatment and clinical
      quality of maternity along the birthing process suggests health system drivers
      that influence provider behaviour and health facility environment should be
      considered for quality improvement and reduction of mistreatment.

PMID- 30212310
TI  - Clinical Gerontologist.

PMID- 30212311
TI  - HEMATOLOGY, PLASMA BIOCHEMISTRY, AND URINALYSIS OF FREE-RANGING GREY-HEADED
      FLYING FOXES ( PTEROPUS POLIOCEPHALUS) IN AUSTRALIA.
AB  - The grey-headed flying fox ( Pteropus poliocephalus) is a species endemic to
      coastal eastern Australia. This study presents a comprehensive set of
      biochemistry, hematology, and urinalysis biomarkers from which reference values
      were derived. Blood samples collected from free-ranging P. poliocephalus were
      submitted for hematology ( n = 140) and plasma biochemistry ( n = 161) and urine
      for urinalysis ( n = 95). The values for P. poliocephalus were broadly consistent
      with those values published for other Australian Pteropus species. Statistically
      significant within-species age and sex effects were observed: adult P.
      poliocephalus had higher mean corpuscular volume, mean corpuscular hemoglobin,
      urea, creatinine, bilirubin, alanine transferase (ALT), protein, globulin,
      urinary specific gravity, and urinary ketones, whereas subadults had higher mean
      red blood cell, white blood cell (WBC), lymphocyte, and monocyte counts, and
      juveniles had higher mean neutrophil count and alkaline phosphatase; male P.
      poliocephalus had higher mean reticulocyte count, alanine transferase, glucose,
      and urinary ketones, whereas females had higher mean WBC, lymphocyte, and
      monocyte counts. The findings inform both clinical and research scenarios for P.
      poliocephalus in captivity or rehabilitation and for health assessments of free
      living populations.

PMID- 30212312
TI  - HEMOLYMPH CHEMISTRY REFERENCE RANGES OF THE CHILEAN ROSE TARANTULA GRAMMOSTOLA
      ROSEA (WALKENAER, 1837) USING THE VETSCAN BIOCHEMISTRY ANALYZER BASED ON IFCC
      CLSI C28-A3.
AB  - The use of invertebrate hemolymph chemistry analysis has the potential to become
      a major diagnostic tool. The goal of this study was to generate statistically
      sound hemolymph reference ranges from healthy tarantulas. Hemolymph was drawn
      from wild caught, acclimatized, and apparently healthy female Chilean rose
      tarantulas Grammostola rosea (Walkenaer, 1837) ( n = 43) using a modified
      technique. Hemolymph samples were separately analyzed using the Avian-Reptilian
      Profile Plus reagent rotor for VetScan(r) for the following chemistries:
      aspartate aminotransferase, bile acids, creatine kinase, uric acid, glucose,
      total calcium, phosphorus, total protein, albumin, potassium, and sodium. With
      this method the authors were able to establish statistically sound reference
      ranges for aspartate aminotransferase, creatine kinase, glucose, phosphorus, and
      total protein. Further in situ studies will determine the practical usability of
      these values in the evaluation of tarantula health.

PMID- 30212313
TI  - SURVEY FOR EQUINE HERPESVIRUSES IN POLAR BEARS ( URSUS MARITIMUS) AND EXOTIC
      EQUIDS HOUSED IN US AZA INSTITUTIONS.
AB  - Infection by equine herpesvirus (EHV) strains (EHV-1, EHV-9) in ursid species,
      including polar bears ( Ursus maritimus), has been associated with neurological
      disease and death. A serosurvey of captive exotic equid and polar bear
      populations in US Association of Zoos and Aquaria institutions was performed to
      determine the prevalence of EHV strains using quantitative polymerase chain
      reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) tests. Equid
      species surveyed included zebra ( Equus spp.), Przewalski's wild horse ( Equus
      ferus przewalskii), Persian onager ( Equus hemionus), and Somali wild ass ( Equus
      africanus somaliensis). A questionnaire regarding husbandry and medical variables
      was distributed to institutions housing polar bears. No polar bears tested
      positive for EHVs on qPCR of blood or nasal swabs. No exotic equids tested
      positive for EHVs on qPCR of blood, but two exotic equids ( n = 2/22; 9%) tested
      positive for EHVs on qPCR of nasal swabs. On ELISA, polar bears infrequently were
      positive for EHV-1 ( n = 5/38; 13%). Exotic equids were positive for EHV-4 on
      ELISA more frequently ( n = 30/43; 70%) than for EHV-1 ( n = 8/43; 19%). Nine
      institutions submitted samples from both exotic equids and polar bears, two of
      which had both exotic equids and polar bears positive for EHVs by ELISA. Each of
      these institutions reported that the polar bear and exotic equid exhibits were
      within 80 m of each other and that risk factors for fomite transmission between
      exhibits based on husbandry practices were present. One institution that did not
      house exotic equids had a polar bear test positive for EHV-1 on ELISA, with no
      history of exposure to exotic equids. Further testing of captive polar bears and
      exotic equids is recommended, as is modification of husbandry practices to limit
      exposure of polar bears to exotic equids.

PMID- 30212314
TI  - OUTBREAK AND TREATMENT OF CARP EDEMA VIRUS IN KOI ( CYPRINUS CARPIO) FROM
      NORTHERN CALIFORNIA.
AB  - Carp edema virus (CEV) is the causative agent of carp edema virus disease (CEVD),
      also referred to as koi sleepy disease, which is an emerging disease of global
      concern that may cause high rates of morbidity and mortality in common carp and
      ornamental koi ( Cyprinus carpio). This article reports the third confirmed
      outbreak of CEVD in California. In June 2015, three koi presented with clinical
      signs of cutaneous lesions, severe lethargy, and signs of hypoxia. All fish
      tested positive for CEV by polymerase chain reaction (PCR). Euthanasia and
      complete necropsy were performed on two fish. The most significant necropsy
      findings included necrotizing branchitis with marked interstitial edema,
      multifocal cutaneous ulcerations, and severe cutaneous edema. Treatment of the
      pond with 0.3-0.5% salt was recommended to the owner. Approximately 7 wk later, a
      recheck visit was made to the pond. No mortalities had been noted since the
      initiation of the salt treatment. Physical examination revealed a vast
      improvement but not complete elimination of the clinical signs of hypoxia and
      intermittent lethargy in the affected fish. Gill biopsy samples from the two most
      affected fish were tested and remained PCR positive for CEV. Subsequent recheck
      visits over 11 mo postdiagnosis and initiation of treatment showed continued
      improvement in most fish. Gill samples from all fish in the pond ( n = 9) were
      repeatedly tested by quantitative PCR for CEV, and all samples were negative.
      This case series further confirms the global spread of CEV and the need for
      practitioners to be vigilant for outbreaks of this disease. If CEVD is suspected,
      treatment with 0.3-0.5% salt can be recommended to potentially mitigate the
      effects of this disease. However, fish may remain potential carriers of this
      pathogen, and strict biosecurity measures should continue to be enforced for any
      pond that has had a confirmed CEV outbreak.

PMID- 30212315
TI  - MOOSE ( ALCES ALCES) MORTALITY ASSOCIATED WITH CAPRINE HERPESVIRUS 2 (CPHV-2) IN
      A ZOOLOGICAL COLLECTION.
AB  - Malignant catarrhal fever (MCF) can affect both domestic and wild artiodactyls.
      In a zoological setting, in which subclinical carriers and susceptible species
      are often housed in close proximity, the disease can prove fatal. This report
      describes a case of goat-associated MCF in a captive moose ( Alces alces). The
      diagnosis was confirmed by histopathology, which showed lymphocytic vasculitis in
      the brain and panuveitis, and by detection of caprine herpesvirus 2 DNA in
      tissues. Identical viral DNA sequences amplified from the clinically affected
      moose and from domestic, petting goats ( Capra aegagrus hircus) housed in the zoo
      suggest that the goats were the source for the virus transmutation. This is the
      first report, to our knowledge, of confirmed goat-associated MCF in any moose in
      North America and of the surveillance measures and procedures put in place to
      prevent additional spread of the disease.

PMID- 30212316
TI  - MOTOR NERVE CONDUCTION VELOCITIES OF THE MEDIAN AND SCIATIC-TIBIAL NERVES IN
      EIGHT NORMAL LARGE FLYING FOXES ( PTEROPUS VAMPYRUS).
AB  - Electrodiagnostic testing is an integral part of the evaluation of the motor unit
      in many neurologic conditions. Literature about the peripheral nervous system of
      flying foxes ( Pteropus spp) is sparse, and reference range values for motor
      nerve conduction velocities in vivo have not been established in Chiropterans.
      The goals of this study were to determine reference range conduction velocities
      in flying fox for the thoracic and pelvic limb nerve. Eight Pteropus vampyrus,
      large flying foxes, of varying ages and gender underwent nerve conduction studies
      of the median nerve and sciatic-tibial nerve. Mean (SD) conduction velocity
      values were 49.8 (12.7) m/sec for the median nerve and 42.1 (10.2) m/sec for the
      sciatic-tibial nerve. Median nerve conduction velocities were not significantly
      faster than sciatic-tibial nerve conduction velocities, although a trend was
      seen. Differences by sex or age class were not statistically significant. It was
      also noted that flying foxes rapidly lose body heat under general anesthesia.

PMID- 30212317
TI  - REFERENCE INTERVALS FOR ERYTHROCYTE SEDIMENTATION RATE, LACTATE, FIBRINOGEN,
      HEMATOLOGY, AND PLASMA PROTEIN ELECTROPHORESIS IN CLINICALLY HEALTHY CAPTIVE
      GOPHER TORTOISES ( GOPHERUS POLYPHEMUS).
AB  - Currently available tests for the diagnosis of inflammatory disease in reptiles
      are limited and poorly sensitive. However, a number of hematological and plasma
      biochemical analytes are validated in the diagnosis of inflammation in mammals.
      The objective of this study was to establish reference intervals for erythrocyte
      sedimentation rate, lactate, heat-precipitated fibrinogen, hematology, and plasma
      protein electrophoresis based on total protein by biuret method in 23 clinically
      healthy, captive gopher tortoises ( Gopherus polyphemus) after successful
      rehabilitation and to determine differences by age, sex, and season. In order to
      investigate biological differences, samples were collected in April, July, and
      November. There were no sex differences in any measured analyte; however, there
      were significant differences by age and season. Immature animals (<2 kg) had
      significantly higher total protein, albumin : globulin ratio, pre-albumin,
      albumin, and alpha-1 globulin than adults. Tortoises sampled in the spring season
      had significantly higher total solids (refractometer) and lower eosinophils
      compared with animals sampled in the summer. Further investigation is required to
      determine the clinical utility of these analytes in the diagnosis of inflammation
      in this species.

PMID- 30212318
TI  - EVALUATION OF TWO ENZYME-LINKED IMMUNOSORBENT ASSAYS MEASURING PREGNANCY
      ASSOCIATED GLYCOPROTEINS IN THE BLOOD OF MUSKOXEN ( OVIBOS MOSCHATUS).
AB  - Pregnancy-associated glycoproteins (PAGs) are expressed by the ruminal placenta,
      making their detection in blood an accurate indicator of pregnancy. This study
      aimed to evaluate two commercially available PAG enzyme-linked immunosorbent
      assays (ELISAs) in muskoxen ( Ovibos moschatus). The two tests are based on the
      same principles; however, one is evaluated photometrically and the other
      visually. Sixteen samples covering all trimesters of pregnancy, and 16
      nonpregnant samples were included to evaluate test performance. Both tests
      reliably detected pregnancy. The photometric ELISA showed a sensitivity and
      specificity of 94% and 100%, respectively. Although the visual ELISA depends on
      somewhat subjective interpretations, it came up with a sensitivity of 81% and a
      specificity of 100%, and might thus provide a useful in-house tool when limited
      laboratory equipment is available. Analysis of additional samples showed
      consistent results during pregnancy and circulating PAGs for at least 18 days
      postpartum.

PMID- 30212319
TI  - COMPARISON OF PROPOFOL CONSTANT RATE INFUSION AND ISOFLURANE FOR MAINTENANCE OF
      ANESTHESIA IN SPEKE'S GAZELLE, GAZELLA SPEKEI.
AB  - The aims of this study were to determine if a propofol constant rate infusion
      (CRI) in Speke's gazelle, Gazella spekei, would serve as an effective alternative
      maintenance anesthetic, result in shorter recovery times, and improve anesthetic
      recovery quality when compared with isoflurane. Eight adult gazelle were enrolled
      in this complete crossover study with a minimum 3-wk washout period. All gazelle
      were induced with 10 mg/kg intravenous propofol and maintained with either
      propofol CRI (0.4 mg/kg/min) or isoflurane (1-3%) for 45 min. Animals were
      monitored for anesthetic depth and physiologic variables including heart and
      respiratory rates, oxygen saturation, end-tidal carbon dioxide, indirect blood
      pressure, and temperature every 5 min. Blood gas samples were analyzed within the
      first 10 min following anesthetic induction and within the last 10 min of
      anesthesia. Recovery times were recorded. Recovery quality was classified by a
      residual ataxia grading scale. Seven gazelle completed the study by undergoing
      both anesthetic treatments; one female (12 yr old) developed complications 2 days
      after isoflurane anesthesia, consisting of seizures, azotemia, leukocytosis,
      hypocalcemia, and hypomagnesemia but was treated successfully. Propofol
      anesthesia resulted in lower respiratory rates compared with isoflurane and a
      decrease in respiratory rate over time. Propofol CRI maintained blood pressure
      values closer to physiologically normal ranges compared with isoflurane for 45
      min of anesthesia. Recovery times were comparable between propofol and isoflurane
      treatments. While individuals receiving propofol had higher residual ataxia
      scores compared with individuals receiving isoflurane, differences were not
      clinically important. This study demonstrated that propofol CRI (0.4 mg/kg/min)
      is an effective maintenance anesthetic agent in healthy adult Speke's gazelle for
      noninvasive procedures with endotracheal intubation and intermittent positive
      pressure ventilation.

PMID- 30212320
TI  - LETTER TO THE EDITOR.

PMID- 30212321
TI  - ABSENCE OF ACUTE TOXICITY OF A SINGLE INTRAMUSCULAR INJECTION OF MELOXICAM IN
      GOLDFISH ( CARASSIUS AURATUS AURATUS): A RANDOMIZED CONTROLLED TRIAL.
AB  - Meloxicam is a nonsteroidal anti-inflammatory drug with preferential
      cyclooxygenase-2 inhibitory activity. It is frequently used in veterinary
      medicine, including in fish species. The efficacy and safety of meloxicam,
      however, has not yet been reported in adult fish. The purpose of this study was
      to evaluate the acute toxicity of a single intramuscular injection of meloxicam
      in goldfish ( Carassius auratus auratus). Following 3 wk of acclimation, 32
      goldfish were randomly assigned to two groups of 16 individuals. Fish from the
      treatment group received a single intramuscular injection of 5 mg/kg meloxicam,
      while the fish from the control group received a single intramuscular injection
      of a 0.9% sodium chloride solution using a similar volume (1 ml/kg). No external
      lesions, mortality, or modifications in behavior or position in the water column
      were noted during the following 72 hr. Three days after the initial injection,
      all fish were euthanized by immersion in a solution of tricaine methanesulfonate.
      Complete postmortem and histologic evaluations were performed for each fish.
      Hemorrhage and muscular necrosis were observed at the site of injection in fish
      from both groups. Multiple granulomas of undetermined etiology were detected in
      numerous organs from fish of both groups. No statistically significant
      differences were detected in regard to the lesions observed in these two groups.
      This study demonstrates that a single intramuscular injection of meloxicam at a
      dosage of 5 mg/kg does not cause acute toxicity in goldfish.

PMID- 30212322
TI  - EVALUATION OF CONJUNCTIVAL MICROBIOTA IN CLINICALLY NORMAL PERSIAN SQUIRRELS (
      SCIURUS ANOMALUS).
AB  - This study aimed to evaluate the bacterial flora in the conjunctival fornix of
      clinically normal Persian squirrels ( Sciurus anomalus). Forty healthy Persian
      squirrels of equal gender distribution with similar ages (approximately 2 yr)
      were used for this study. A total of 80 conjunctival swabs were taken from both
      the right and left eyes of each squirrel for aerobic and anaerobic bacterial
      identification. A slit-lamp examination was conducted and no external ocular
      disease was identified. From 80 normal eyes, Staphylococcus spp. comprised the
      most frequently isolated organism (83%), while Corynebacterium spp. were the
      second most frequently isolated bacteria (56%), followed by Streptococcus spp.
      (53%), Chlamydia spp. (33%). Mycoplasma spp. (30%), Pseudomonas spp. (23%),
      Escherichia coli spp. (12.5%), Enterococcus spp. (7%), and Micrococcus spp. (4%)
      were also isolated. The most frequently isolated bacteria from the conjunctival
      fornix of healthy Persian squirrels were Staphylococcus spp. followed by
      Corynebacterium spp.

PMID- 30212323
TI  - ENVIRONMENTAL FUNGAL LOADS IN AN INDOOR-OUTDOOR AFRICAN PENGUIN ( SPHENISCUS
      DEMERSUS) EXHIBIT.
AB  - Aspergillosis continues to be one of the most important causes of disease in
      captive penguins. As such, designing exhibits and holding areas that minimize the
      risk of aspergillosis is of great interest; however, very little has been
      published regarding this topic. The goal of this study was to assess total fungal
      spore loads as well as the loads of Aspergillus spp. encountered in multiple
      indoor and outdoor microenvironments around the exhibit for a large colony of
      African penguins ( Spheniscus demersus). Air samples were collected via impaction
      at the microenvironments on a monthly basis over a 1-yr period. Results of this
      study indicated seasonal trends in both total fungal spore loads as well as
      Aspergillus spp. loads, with the lowest levels encountered during January through
      April. During the warmer, more humid spring, summer, and fall months when outdoor
      microenvironments experienced the highest fungal loads, the air-handling system
      and the pleated filters used indoors are thought to have reduced the fungal loads
      in the indoor microenvironments compared with the outdoor microenvironments.
      Additionally, surrounding planting beds were thought to contribute to the higher
      total fungal loads and Aspergillus spp. loads in the outdoor microenvironments.
      Results of this study are useful in understanding the factors that contribute to
      Aspergillus spp. loads in areas that house penguins, and can be used in guiding
      design, construction, and landscaping of penguin enclosures.

PMID- 30212324
TI  - A PRELIMINARY ANALYSIS OF PROLONGED ABSORPTION RATE OF PONAZURIL IN RED-FOOTED
      TORTOISES, CHELONOIDIS CARBONARIA.
AB  - Coccidial disease is significant in tortoises; Testudines intranuclear
      coccidiosis (TINC), caused by an unnamed coccidia, causes high mortality in
      diverse tortoise species. There is a lack of information on anticoccidial drugs
      in tortoises. The drug ponazuril has demonstrated efficacy in treating mammals
      infected with similar coccidial disease. Previous empirical use of ponazuril in
      TINC cases suggests that it may be an effective treatment. In this study, 20
      mg/kg of ponazuril was orally administered to tortoises with the goal of
      achieving blood concentrations known to be effective for anticoccidial therapy in
      mammals. Ponazuril was measured in tortoise plasma, and noncompartmental analyses
      of pharmacokinetic parameters were attempted. Ponazuril in these tortoises did
      not achieve the desired concentrations known to be effective for anticoccidial
      treatment in mammals. Tortoises showed prolonged oral absorption, and despite
      sampling for 168 hr (1 wk), a terminal elimination rate constant and half-life
      were not able to be determined. Additional studies are needed to fully
      characterize ponazuril pharmacokinetics in red-footed tortoises. The optimal dose
      for treating TINC remains to be determined.

PMID- 30212325
TI  - PAROTID CARCINOMA IN A FREE-RANGING CALIFORNIA SEA LION ( ZALOPHUS
      CALIFORNIANUS).
AB  - A free-ranging juvenile California sea lion ( Zalophus californianus) stranded on
      the coast of Vancouver, British Columbia, with signs of lethargy and emaciation
      in April 2016. An asymmetrical skull with a prominent superficial cervical lymph
      node was found on initial assessment. Fine-needle aspirates and biopsies of the
      lymph node were consistent with neoplasia and the animal was humanely euthanized
      and presented for necropsy. A metastatic parotid gland adenocarcinoma was
      diagnosed with regional lymph node and pulmonary metastases. Local invasion of
      contiguous skeletal muscle, bone, ear, and tonsils was extensive and likely
      accounted for the unilateral craniofacial deformity. Neoplasia of nonurogenital
      origin in juvenile California sea lions are reported infrequently. This is the
      first case of a parotid carcinoma in a California sea lion.

PMID- 30212326
TI  - IDIOPATHIC IRON OVERLOAD IN A HARBOR SEAL ( PHOCA VITULINA).
AB  - Iron overload has been described in various wild species. The majority of cases
      involve captive animals, often associated with increased dietary iron uptake.
      Here a case of idiopathic iron overload in a female adult harbor seal under human
      care is presented. The animal displayed a progressive anorexia, apathy, and
      increased serum iron levels. Radiographs showed radiopaque foreign bodies in the
      stomach. The seal died during an elective laparotomy. Twenty-five coins and two
      metal rings were removed from the stomach. Histopathologic examination revealed
      iron storage without cellular damage in liver, spleen, kidney, and pulmonary and
      mesenteric lymph nodes. Atomic absorption spectrophotometry analysis for iron
      revealed values thirty times above the reference ranges in spleen and liver;
      however, the coins only contain minor levels (parts per million) of iron. The
      etiology of the iron overload in this animal remains unclear. A multifactorial
      process cannot be excluded.

PMID- 30212327
TI  - GASTRIC PYTHIOSIS IN A BACTRIAN CAMEL ( BACTRIANUS CAMELUS).
AB  - Pythium insidiosum, an aquatic oomycete, causes chronic lesions in the skin and
      digestive tract of multiple species. A captive-bred Bactrian camel ( Camelus
      bactrianus) showed clinical signs of lethargy and weight loss in a clinical
      course of 30 days, with no response to treatment. At necropsy, the abdominal
      cavity had approximately 32 L of a yellow, turbid fluid with fibrin. The third
      compartment of the stomach (C-3) showed a focal area of rupture covered with
      fibrin. Close to this area, the C-3 wall was thickened and firm, demonstrating
      irregular, yellow, and friable areas on cut surface (kunkers). Microscopically,
      these corresponded to necrosis, characterized by a central amorphous eosinophilic
      material, surrounded by a pyogranulomatous inflammatory infiltrate and fibrosis.
      Negatively stained hyphae were observed at the periphery of the necrotic areas,
      which showed marked immunostaining for P. insidiosum. Pythiosis in camelids may
      involve the stomach, resulting in peritonitis and death.

PMID- 30212328
TI  - APPLICATION OF 3-HYDROXYBUTYRATE MEASUREMENT AND PLASMA PROTEIN ELECTROPHORESIS
      IN THE DIAGNOSIS OF ASPERGILLOSIS IN AFRICAN PENGUINS ( SPHENISCUS DEMERSUS).
AB  - New alternative laboratory means are needed to improve the options for antemortem
      diagnosis of avian aspergillosis. In this study, 3-hydroxybutyrate was measured
      in plasma samples collected from a cohort of African penguins ( Spheniscus
      demersus) maintained under human care. Results were interpreted in combination
      with those of protein electrophoresis and compared with anti- Aspergillus
      antibody and galactomannan antigen detection. Overall, 3-hydroxybutyrate levels
      were found significantly increased in Aspergillus-diseased cases versus the
      control penguin group ( P = 0.002). Mean absolute concentration of beta-globulins
      was increased >20% in samples from infected birds, and alpha2-globublins were
      also found to be significantly increased versus clinically normal controls ( P <
      0.001 and P = 0.001 respectively). Of note, the alpha2-globulins were also
      significantly increased versus penguins with inflammatory (non-aspergillosis)
      diseases ( P = 0.001). The specificity of 3-hydroxybutyrate, beta-globulins, and
      alpha2-globulins for aspergillosis was 78.6%, 79.6%, and 92.2%, respectively.
      Using these measures in tandem resulted in high specificity (>90%) and negative
      predictive value (>=80%). In contrast, anti- Aspergillus antibody and
      galactomannan antigen did not distinguish between infected cases and controls ( P
      > 0.05). This study demonstrates that basic testing in tandem with the new
      biomarker 3-hydroxybutyrate may provide reliable evidence for the diagnosis of
      aspergillosis in penguins.

PMID- 30212329
TI  - IMMUNOHISTOCHEMICAL AND MOLECULAR EVIDENCE OF PUTATIVE NEORICKETTSIA INFECTION IN
      COATIS ( NASUA NASUA) FROM SOUTHERN BRAZIL.
AB  - The pathologic, molecular, and immunohistochemical findings associated with
      Neorickettsia helminthoeca are described in coatis ( Nasua nasua). Tissue
      sections (small intestine, lungs, kidney, liver, and spleen) of coatis ( n = 3)
      that died at the Bela Vista Biological Refuge, Foz do Iguacu, Parana, southern
      Brazil were routinely processed from histopathology. Selected formalin-fixed
      paraffin-embedded (FFPE) tissue sections of the small intestine, lungs, and
      spleen were used in an immunohistochemical (IHC) assay designed to identify the
      antigens of N. helminthoeca. Additionally, FFPE tissue sections of the small
      intestine were used to demonstrate antigens of canine parvovirus-2 (CPV-2) by
      IHC. Histopathology revealed chronic enteritis in all coatis. Parasitic enteritis
      was diagnosed in two coatis; one of these contained examples of a trematode
      within the lumen of the small intestine and the ovum of a trematode encysted in
      the intestinal mucosa. Other significant pathologic findings included
      interstitial pneumonia ( n = 2) and pyogranulomatous splenitis ( n = 1). Positive
      immunolabeling for N. helminthoeca was identified within macrophages of the small
      intestine and reticuloendothelial cells within the germinal centers of the spleen
      of all coatis; the intestinal trematode was N. helminthoeca IHC-positive. All
      pulmonary sections revealed negative immunolabeling for N. helminthoeca.
      Furthermore, the antigens of CPV-2 were not identified in the intestine of any
      coati. These findings indicate that these coatis were infected by N.
      helminthoeca, but since clinical and gross pathological findings were not
      recorded, it is uncertain if this pathogen produced clinical disease in this
      canid host; therefore, coatis may be asymptomatic or dead-end hosts for this
      organism.

PMID- 30212330
TI  - RADIOGRAPHIC EVALUATION OF CARDIAC SILHOUETTE IN CLINICALLY HEALTHY HUMBOLDT
      PENGUINS ( SPHENISCUS HUMBOLDTI).
AB  - Wild populations of Humboldt penguins ( Spheniscus humboldti) on the coasts of
      Chile and Peru have been declining because of food scarcity caused by the El Nino
      Southern Oscillation and human interference. Part of conserving this vulnerable
      and threatened species is maintaining the health of penguins within zoo
      collections. A variety of cardiovascular diseases has been reported in
      individuals from the Spheniscidae family including ventricular septal defects,
      Dirofilaria immitis infection, pulmonary hypertension, and valvular dysplasia,
      ultimately resulting in congestive heart failure. An accurate clinical picture of
      cardiovascular disease in Humboldt penguins requires diagnostics tailored to this
      specific species. The aim of this study was to establish a routine methodology
      for evaluating the cardiac silhouette of clinically healthy Humboldt penguins
      using vertebral heart scale (VHS), cardiocoelomic width ratio (CCWR), and a novel
      cardiac silhouette-to-keel ratio (CKR). Ventrodorsal and right lateral
      radiographs were taken of 10 mature Humboldt penguins during routine health
      evaluations. An echocardiographic exam of each penguin was performed to confirm
      that there was no evidence of cardiac structural remodeling from disease. Two
      penguins were excluded on the basis of echocardiographic findings; therefore,
      data from eight penguins were used to calculate objective cardiac measurements
      for the clinically healthy population. Right lateral radiographs were used to
      determine VHS (7.4-10.4) and CKR (3.4-4.4). Ventrodorsal radiographs were used
      for calculating CCWR (0.45-0.59). The excluded penguins had CCWRs that were
      outside the 95% confidence interval for the range generated by this study. This
      initial work supports that standardizing radiographic views provides objective
      measures for cardiac silhouette evaluation in this species. Further research in
      larger populations and comparison with birds having confirmed cardiac disease is
      needed to determine the value of these three measurement techniques in Humboldt
      penguins.

PMID- 30212331
TI  - NEW APPROACH TO STRESS RESEARCH IN PHOCIDS-POTENTIAL OF DEHYDROEPIANDROSTERONE
      AND CORTISOL/DEHYDROEPIANDROSTERONE RATIO AS MARKERS FOR STRESS IN HARBOR SEALS (
      PHOCA VITULINA) AND GRAY SEALS ( HALICHOERUS GRYPUS).
AB  - Cortisol is known to reflect the level of the stress response. However, measuring
      the cortisol concentration only once fails to provide sufficient information
      about the duration of the stress exposure. Moreover, handling is an acute
      stressor and increases cortisol secretion especially in wildlife species. Yet, in
      phocids reliable indicators are missing that reflect potential chronic effects of
      stress. The adrenal-derived steroid hormone dehydroepiandrosterone (DHEA) has
      been described as biomarker for the assessment of the stress status but has not
      been applied to marine mammal stress research. Therefore, DHEA, the sulfated
      precursor DHEAS and the cortisol/DHEA ratio were determined in serum of different
      seals. One group consisted of harbor ( Phoca vitulina) and gray seals (
      Halichoerus grypus) that were habituated to human handling. The other two groups
      included healthy and free-ranging seals suffering from a disease. Blood samples
      were taken from 11 habituated (six males, five females), 17 wild_healthy (13
      males, four females), and nine wild_diseased seals (four males, five females). No
      differences in serum cortisol levels could be detected between wild_healthy and
      wild_diseased seals. On the contrary, wild_diseased seals showed the lowest DHEA
      concentration compared to the other two groups. Wild_diseased seals also revealed
      the highest cortisol/DHEA ratio compared to the habituated_zoo (2,074.7 +/- 351.4
      vs. 121.5 +/- 26.8, P < 0.001) and wild_healthy seals (827.9 +/- 214.3, P <
      0.01). DHEA and the cortisol/DHEA ratio may reflect differences in the
      functionality of the hypothalamic-pituitary-adrenal axis and therefore represent
      valuable tools for the assessment of stress-related effects in seals.

PMID- 30212332
TI  - OUTBREAK OF MYCOBACTERIUM TUBERCULOSIS IN A HERD OF CAPTIVE ASIAN ELEPHANTS (
      ELEPHAS MAXIMUS): ANTEMORTEM DIAGNOSIS, TREATMENT, AND LESSONS LEARNED.
AB  - Tuberculosis (TB) was diagnosed in four Asian elephants ( Elephas maximus) in a
      zoo in the United States. The first case was detected by isolation of
      Mycobacterium tuberculosis during routine trunk wash (TW) culture testing of a
      herd of eight elephants. Retrospective antibody analyses revealed seroconversion
      1 yr before diagnosis. Serological testing of the whole elephant herd identified
      two additional suspect bulls with detectable antibody, but which remained culture
      negative and had no clinical signs of disease. In the following months, M.
      tuberculosis, identical to the isolate from the index case, was isolated from TW
      samples of these two elephants. A fourth elephant seroconverted nearly 4 yr after
      the first TB case was detected, and M. tuberculosis was isolated from a TW sample
      collected 1 mo later. All four infected elephants received anti-TB therapy. Two
      treated elephants were eventually euthanized for reasons unrelated to M.
      tuberculosis and found to be culture-negative on necropsy, although one of them
      had PCR-positive lung lesions. One infected animal had to be euthanized due to
      development of a drug-resistant strain of M. tuberculosis; this animal did not
      undergo postmortem examination due to risk of staff exposure. The fourth animal
      is currently on treatment. Serial serological and culture results of the other
      four herd mates have remained negative.

PMID- 30212333
TI  - STRECK CELL PRESERVATIVE STABILIZES KOALA ( PHASCOLARCTOS CINEREUS) WHOLE BLOOD
      FOR COMPLETE BLOOD COUNTS.
AB  - Wildlife health assessments at remote sites may lead to delayed testing of whole
      blood for complete blood counts (CBC) resulting in artifacts affecting clinical
      interpretation. Streck Cell Preservative (SCP) is a proprietary liquid
      stabilization reagent designed to preserve human leukocytes and may be applicable
      to wildlife health assessments when immediate processing of blood is not
      possible. The purpose of this study was to determine if SCP adequately preserved
      EDTA-anticoagulated whole blood from koalas ( Phascolarctos cinereus) for up to
      14 days. Blood from 12 captive adult koalas was collected and combined with SCP
      in a 1 : 1 ratio and refrigerated. Paired samples of SCP treated and untreated
      blood had CBCs performed at five time-points over 14 days. Streck Cell
      Preservative extended koala EDTA-anticoagulated whole blood viability to 14 days
      by decreasing cellular lysis. Species- and method-specific reference intervals
      for SCP should be generated to avoid clinical misinterpretation, especially when
      evaluating anemia.

PMID- 30212334
TI  - AORTIC ANEURYSM, DISSECTION, AND RUPTURE IN SIX BILE-FARMED BEARS.
AB  - Across China and Southeast Asia, over 17,000 bears are currently farmed for bile,
      predominantly for traditional Chinese medicines. Bears on farms in China are cage
      confined and undergo repeated daily bile extraction facilitated by surgically
      implanted catheters or gallbladder fistulas. Numerous health problems have been
      reported in bile-farmed bears including peritonitis, abdominal hernias, and
      extraction site abscessation. Between 2009 and 2014, five Asiatic black bears (
      Ursus thibetanus) and one Asiatic black/Eurasian brown bear ( Ursus arctos
      arctos) hybrid, rescued from the bear bile industry in China, died from ruptured
      and/or dissecting aortic aneurysm. Medical records were reviewed and two bears
      exhibited no clinical signs prior to death. In four bears, clinical findings
      varied and included increased stereotypic behavior prior to death, epistaxis,
      retinal lesions, dysphagia, weight loss, and acute onset of hyporexia. On
      postmortem examination, hemopericardium with dissection and/or rupture of the
      ascending aorta and left ventricular wall hypertrophy were present in all cases.
      No evidence of infectious disease, connective tissue disorders, or congenital
      cardiac disease was identified. Based on these observations screening thoracic
      radiography was performed on all bears at the rescue center and aortic dilation
      was identified in 73 of 134 (54.5%) bile-extracted bears. To the authors'
      knowledge, aortic aneurysm, rupture, and/or dissection have not been previously
      reported in any bear species and the high prevalence in this population of bears
      suggests an association with bile-farming practices. Future studies are needed to
      investigate the etiopathogenesis of this condition to aid in early diagnosis and
      improved management of bears being rescued from bile farms across Asia.

PMID- 30212335
TI  - OSTEOCHONDRAL AUTOGRAFT TRANSFER FOR TREATMENT OF STIFLE OSTEOCHONDRITIS
      DISSECANS IN TWO RELATED SNOW LEOPARDS ( PANTHERA UNCIA).
AB  - Two related female snow leopards ( Panthera uncia) were diagnosed with
      osteochondritis dissecans of the lateral femoral condyle via radiographs and
      computed tomography. Lesions were either bilateral (Patient 1) or unilateral
      (Patient 2). Surgical treatment was performed using an osteochondral autograft
      transfer system following cartilage flap removal. After a 6-wk recovery period,
      both animals had a markedly improved gait with mild pelvic limb stiffness.
      Patient 1 developed intermittent lameness 9 mo postsurgery and Patient 2 had mild
      lameness 3 yr postsurgery. Because of recurrent lameness, both animals were
      treated with platelet-rich plasma intra-articular injections and oral gabapentin
      (Patient 1) or oral meloxicam (Patient 2). Full incorporation of autografts was
      confirmed with computed tomography (both patients) and arthroscopy (Patient 1
      only). Osteochondritis dissecans has been previously reported in snow leopards
      and these cases represent the first reported use of osteochondral autograft
      repair and platelet-rich plasma to treat the condition.

PMID- 30212336
TI  - RETROSPECTIVE MORTALITY REVIEW OF SIX CALLITRICHID SPECIES HOUSED AT A SINGLE
      INSTITUTION (1990-2014).
AB  - Callitrichids are commonly exhibited species in zoological institutions.
      Retrospective mortality studies allow institutions to evaluate health trends in
      captive populations and have the potential to advance zoological medicine and
      husbandry practices. In this single institution, retrospective study,
      histopathologic records were reviewed for 166 callitrichids comprising six
      species. For all species and age-groups combined, trauma was the leading cause of
      death followed by enteritis and stillbirth. In adults and juveniles, the leading
      cause of death was enteritis, with neonates dying primarily from trauma. Neonatal
      mortality was high for most species, ranging from 12.5% to 60%, with most
      neonatal loss in Geoffroy's and pied tamarins. Twin births were commonly
      associated with neonatal mortality in most species. Intestinal adenocarcinoma was
      a common finding for adult Geoffroy's tamarin, and hemosiderosis was also
      identified in this species. Renal disease was a common finding in adult
      callitrichids and was the second most common cause of death in this age-group.
      Mortality in the juvenile period (>30 days-1 yr) was uncommon, comprising only
      8.4% of the data set. Although capable of surviving into advanced age (>20 yr for
      one animal), the average age at death for all age classes was 3.84 yr and 9.31 yr
      for adults. This study contributes to the current knowledge regarding trends in
      callitrichid health and husbandry and can be used to investigate health trends in
      this group.

PMID- 30212337
TI  - MILK COMPOSITION OF INDIAN RHINOCEROS ( RHINOCEROS UNICORNIS) AND CHANGES OVER
      LACTATION.
AB  - The objective of this study was to determine the major nutrient composition of
      Indian rhinoceros milk ( Rhinoceros unicornis) over the first 13 mo of an 18-mo
      lactation period and to compare the results to those of previous studies on
      rhinoceros, African elephant ( Loxodonta africana), and horse milk ( Equus ferus
      caballus). The following parameters were measured: dry matter (DM), crude ash
      (ASH), crude protein (CP), ether extract (EE), nitrogen-free extract (NFE;
      calculated), lactose, calcium (Ca), phosphorus (P), magnesium (Mg), fatty acids
      (FAs), and gross energy (GE). DM, ASH, CP, and EE were determined with a
      proximate analysis, lactose with infrared spectroscopy and an enzymatic method,
      minerals with an autoanalyzer, FA with gas chromatography, and GE with bomb
      calorimetry. Milk samples were collected from two Indian rhinoceros cows from Zoo
      Basel. Rhino A gave birth to her third calf on 10 September 2012; three samples
      were collected and analyzed (colostrum, milk 1 wk and 2 wk postpartum). Rhino B
      gave birth to her eighth calf on 05 October 2013; samples were collected and 15
      were chosen for the analyses (from colostrum to 13 mo postpartum). The
      composition of rhino B's colostrum was 13.8% DM (wet-weight basis), 4.8% ASH,
      61.8% CP, 0.7% EE, 32.6% NFE, 26.7% lactose, 0.59% Ca, 0.54% P, 0.2% Mg (DM
      basis), and 20.3 MJ GE/kg DM. Rhino B's sample collected 13 mo postpartum
      averaged 8.0% DM (wet-weight basis), 3.6% ASH, 16.3% CP, 1.8% EE, 78.3% NFE,
      84.7% lactose, 0.54% Ca, 0.48% P, 0.09% Mg (on DM basis), and 17.43 MJ GE/kg DM.
      The main FAs in rhino B's and rhino A's samples were C10 : 0, C12 : 0, C16 : 0,
      C18 : 1n9c, and C18 : 2n6c. Milk of the Indian rhinoceros is low in fat and
      protein but high in lactose, which is comparable to the milk composition of other
      rhinoceros species and horses, but not African elephants.

PMID- 30212338
TI  - RISK ANALYSIS: CHANGING THE QUARANTINE PARADIGM?
AB  - As modern zoos evolved from menageries, quarantine practices were developed to
      protect animal collections from the introduction of diseases that might arrive
      with new animals from wild populations and, more recently, from other managed
      populations. As the understanding of, and ability to diagnose, diseases grew
      tremendously in recent decades, quarantine protocols became more stringent and
      standardized as the tolerance for disease introduction decreased. These practices
      resulted in healthier animal collections, and the introduction of transmissible
      pathogens of concern became rarer. Sustainable population management in zoos has
      further lessened the reliance on taking animals from the wild, and the knowledge
      of disease risk in such situations has deepened. Today animals being transferred
      between modern zoological institutions have well-documented medical histories
      complemented with robust collection health histories. This improved understanding
      has reduced concerns about disease transmission in many cases. Consequently, more
      formal use of risk analysis to drive transfer-related examination, diagnostic
      testing, and quarantine decision making was adopted by a number of zoos and
      aquariums that have modified their quarantine practices and use risk analysis to
      reduce quarantine requirements, in some cases moving animals directly into
      collections after transportation. This commentary discusses the rationale for and
      changes to quarantine processes for animal acquisitions in zoos and aquariums,
      using risk analysis to direct decision making.

PMID- 30212339
TI  - NEOSPORA CANINUM-SPECIFIC ANTIBODIES IN FREE-RANGING WHITE-LIPPED PECCARIES (
      TAYASSU PECARI) FROM THE PERUVIAN AMAZON: DETECTION OF ANTIBODIES IN SERUM AND
      EVALUATION OF INDIRECT FLUORESCENT ANTIBODY TEST WITH HETEROLOGOUS SECONDARY
      ANTIBODY.
AB  - Neospora caninum is a coccidian parasite originally reported in dogs and widely
      prevalent in numerous species of wild and domestic animals and has as definitive
      hosts some species of canids. The white-lipped peccary (WLP) ( Tayassu pecari) is
      a Tayassuidae mammal, found from Mexico to south of Brazil and north of
      Argentina. It is a game species with great economic importance in the Peruvian
      Amazon. Blood samples from 101 WLPs were collected from near or within three
      different conservation reserves located in the southeastern region of the
      Peruvian Amazon. For the detection of antibodies against N. caninum, indirect
      fluorescent antibody tests (IFAT) were performed using collared peccary ( Pecari
      tajacu) and swine ( Sus scrofa domesticus) heterologous secondary antibodies. For
      both IFAT tests, the cutoff was 1:50. Positive samples were titrated by a two
      fold serial dilution. In addition to IFAT, samples were also analyzed using an
      immunoblotting test (IB) with anti-swine conjugate. To confirm the viability of
      the anti-swine conjugate, the results of these samples previously tested by a
      modified agglutination test (MAT) for Toxoplasma gondii were used as reference.
      From the total of 101 samples tested, 5 (4.9%) were N. caninum positive by the
      three tests and an extra sample was positive by both IFATs and negative in the
      IB. Comparing both IFATs and considering IB as the gold standard, the relative
      sensitivity of IFATs was 100%, the specificity was 98.9%, the positive predictive
      value was 83.3%, and the negative predictive value was 100%. The agreement
      between tests was characterized by a kappa value of 0.904 (95% confidence
      interval, 0.717 to 1.0) and an SE of 0.095. This is the first report of N.
      caninum antibodies in free-ranging T. pecari, and swine and collared peccary
      conjugate can be used as a secondary antibody for detection of antibodies in
      Tayassu species.

PMID- 30212340
TI  - SERUM COBALAMIN AND FOLATE CONCENTRATIONS AS INDICATORS OF GASTROINTESTINAL
      DISEASE IN KILLER WHALES ( ORCINUS ORCA).
AB  - Cobalamin and folate are water-soluble vitamins that are useful indicators of
      chronic gastrointestinal (GI) function in humans and some animal species. Serum
      cobalamin and folate concentrations in an ex situ population of killer whales (
      Orcinus orca) were measured and factors that may affect their serum
      concentrations were identified. Serum samples ( n = 104) were analyzed from
      killer whales ( n = 10) both while clinically healthy and during periods of
      clinical GI disease as defined by clinical signs and fecal cytology. To
      characterize serum cobalamin and folate concentrations in clinically healthy
      animals, a mixed-model regression was used, with cobalamin and folate both
      significantly affected by weight (cobalamin: P < 0.0001, folate: P = 0.006) and
      season (cobalamin: P < 0.0001, folate: P < 0.0001). The marginal mean
      concentrations for cobalamin and folate across weight and season were 742 +/-
      53.6 ng/L and 30.2 +/- 2.6 MUg/L, respectively. The predicted 95% confidence
      intervals (CI) for these analytes were then compared with samples collected
      during periods of GI disease. Across individuals, 22% (2/9) of the folate and 80%
      (8/10) of the cobalamin samples from the animals with GI disease fell outside the
      95% CI for the population. When comparing samples within an individual, a similar
      pattern presented, with 100% of cobalamin of the observed abnormal samples
      reduced compared to healthy animal concentration variability. The same was not
      true for folate. These results suggest that serum concentrations of cobalamin and
      folate may be useful minimally invasive markers to identify GI disease in killer
      whales, especially when values are compared within an individual.

PMID- 30212341
TI  - MAMMARY FIBROADENOMATOUS HYPERPLASIA IN A JUVENILE CALIFORNIA SEA LION ( ZALOPHUS
      CALIFORNIANUS).
AB  - A juvenile female California sea lion ( Zalophus californianus) presented with a
      firm subcutaneous mass in the right caudoventral pelvic region, measuring
      approximately 15 * 15 cm, and edema in the right hind flipper. The initial
      diagnostic workup included an ultrasound, blood analysis, and fine-needle
      aspirate of the mass under manual restraint. While the blood analysis was within
      normal limits, the ultrasound revealed a large discrete hyperechoic homogeneous
      mass with anastomosing hypoechoic fluid pockets that, when aspirated, was
      suggestive of a reactive lymph node. Short-term empiric antibiotic therapy
      prescribed to address possible lymphadenitis yielded no response, and edema of
      the right hind flipper and perianal region worsened. The sea lion was
      anesthetized to facilitate a more thorough exam, repeat blood analysis, obtain
      survey radiographs, evaluate with ultrasound, and perform biopsy of mass. The
      thoracic radiographs were normal; however, the large radiopaque mass was observed
      cranial to the pelvis on lateral abdominal view and appeared solitary on
      ultrasound. An exploratory surgery was performed to completely excise the mass.
      On histopathologic review, the mass demonstrated diffuse fibrous hyperplasia of
      lobular ducts of the mammary gland and mild mastitis, characterizing it as a
      mammary fibroadenoma. The surgical wound healed within 6 wk, and there was no
      recurrence of mammary hyperplasia.

PMID- 30212342
TI  - ANTEMORTEM DIAGNOSIS AND SUCCESSFUL TREATMENT OF A COMPLETE MOLAR PREGNANCY IN A
      GERIATRIC BONOBO ( PAN PANISCUS).
AB  - A 47-yr-old multiparous female bonobo ( Pan paniscus) tested positive for
      pregnancy on a routine urine test. Because this geriatric animal was considered
      postreproductive, oral contraception had been discontinued. Sequential
      transabdominal ultrasound evaluations were performed under voluntary behavior and
      revealed that the uterus contained a mass of heterogenous tissue which was
      rapidly increasing in size. Due to a lack of normal fetal development and the
      ultrasonographic appearance of the uterine tissue, a molar pregnancy was
      suspected. Ovariohysterectomy was performed, and a complete hydatidiform mole was
      confirmed through human chorionic gonadotropin levels as well as gross and
      histological examination of the uterus. To the authors' knowledge, this is the
      first time a complete molar pregnancy has been reported antemortem in a nonhuman
      great ape, although a single case of partial hydatidiform mole was previously
      documented in a chimpanzee on postmortem examination. This case describes the
      successful medical and surgical management of complete molar pregnancy in a
      bonobo and provides support for extending the age range of birth control
      recommendations in geriatric captive great apes that exhibit active breeding
      behavior.

PMID- 30212343
TI  - COMPARISON OF A SMARTPHONE-BASED ELECTROCARDIOGRAM DEVICE WITH A STANDARD SIX
      LEAD ELECTROCARDIOGRAM IN THE ATLANTIC BOTTLENOSE DOLPHIN ( TURSIOPS TRUNCATUS).
AB  - A bipolar, single-lead electrocardiogram (ECG) device is capable of recording
      ECGs with an integrated smartphone application. To determine the utility of this
      device, phone-based ECGs (pECG) were compared with standard six-lead ECGs (sECG)
      in four female Atlantic bottlenose dolphins ( Tursiops truncatus) at the National
      Aquarium. Study animals were trained to haul out onto a dry deck in ventral
      recumbency and allow simultaneous 30-sec ECG acquisition using the two devices.
      The pECG device was held against the thoracic wall caudal to the left axilla. The
      sECGs were recorded in the frontal plane. Instantaneous heart rates were obtained
      from identical QRS complexes on both ECGs. Three boarded cardiologists
      independently evaluated the rhythm and the polarity of the QRS depolarization for
      each recording and the results were compared. The mean heart rate was 80
      beats/min (range 62-92 beats/min) and 80 beats/min (range 60-92 beats/min) for
      the pECG and sECGs, respectively. All four dolphins displayed sinus respiratory
      arrhythmia, and one animal had occasional atrial premature contractions. Rhythm
      diagnosis and QRS polarity were identical for the pECG and sECG. Dolphin
      vocalizations created artifacts on the pECG that were not present on the sECG, so
      pECGs had to be acquired without vocalization. The pECG appears to be an accurate
      and useful method to monitor the heart rate in Atlantic bottlenose dolphins. This
      system is inexpensive and portable, making it valuable for health examinations,
      transport monitoring, and stranding responses.

PMID- 30212344
TI  - INHALANT ANESTHETIC RECOVERY FOLLOWING INTRAMUSCULAR EPINEPHRINE IN THE
      LOGGERHEAD SEA TURTLE ( CARETTA CARETTA).
AB  - Prolonged anesthetic recovery time is a common complication of chelonian inhalant
      anesthesia and may be exacerbated by right-to-left intracardiac shunting of
      blood. Epinephrine may decrease intracardiac shunting, which may shorten
      anesthetic recovery time. The study objective was to assess inhalant anesthetic
      recovery time following intramuscular epinephrine compared with saline in the
      loggerhead sea turtle ( Caretta caretta). With the use of a prospective,
      randomized, blinded, crossover design with a 1-wk washout period, six turtles
      were anesthetized with intravenous (IV) alfaxalone 3 mg/kg, orotracheally
      intubated, manually ventilated with 3.5% isoflurane inhalant in 100% oxygen for
      90 min, and administered either intramuscular (IM) epinephrine 0.1 mg/kg or IM
      saline 0.1 ml/kg. Isoflurane administration was immediately discontinued and
      turtles were manually ventilated with room air until extubation. Physiologic
      variables, sedation scores, end-tidal carbon dioxide (ETCO2) and isoflurane
      (ETISO) concentrations, time to first movement, and time to extubation were
      recorded and two-time-point venous blood gas analyses performed. Data were
      compared with the use of paired t-tests and repeated-measures analyses of
      variance (ANOVA) ( P < 0.05). No morbidity, mortality, or adverse events
      occurred. ETCO2 and ETISO did not significantly change over time during the
      isoflurane delivery period ( P = 0.990). Mean time to first movement was
      significantly faster following epinephrine (69.24 +/- 12.28 min) compared with
      saline (87.71 +/- 27.05 min, P = 0.047). Although differences were not
      statistically significant ( P = 0.133), time to extubation was at least 30 min
      faster (31-123 min) in 4/6 turtles following epinephrine compared with saline.
      Intramuscular epinephrine significantly reduces time to first movement during
      isoflurane anesthetic recovery in loggerhead sea turtles.

PMID- 30212345
TI  - COMPARISON OF THE EFFICACY AND SAFETY OF MEDETOMIDINE-KETAMINE VERSUS
      MEDETOMIDINE-AZAPERONE-ALFAXALONE COMBINATION IN FREE-RANGING ROCKY MOUNTAIN
      BIGHORN SHEEP ( OVIS CANADENSIS).
AB  - Chemical immobilization is a key aspect of wildlife management. To minimize dose
      dependent adverse effects, immobilization protocols often include two or more
      synergistic agents, which allows for reductions in individual drug dosages. Free
      ranging bighorn sheep ( Ovis canadensis) in Canada ( n = 74) were remotely
      injected with a combination of medetomidine (0.16 +/- 0.04 mg/kg) and ketamine
      (4.0 +/- 1.4 mg/kg) (MK), or combination of medetomidine (0.14 +/- 0.06 mg/kg),
      azaperone (0.21 +/- 0.11 mg/kg), and alfaxalone (0.45 +/- 0.21 mg/kg) (MAA). Once
      recumbency was achieved, arterial blood samples were collected and immediately
      analyzed for blood gas and acid-base status. Rectal temperature, heart rate, and
      respiratory rate were recorded upon recumbency and throughout anesthesia at 5-15
      min intervals. At conclusion of the procedures, medetomidine was reversed by
      intramuscular atipamezole at five times the medetomidine dose. Induction times
      (mean +/- standard deviation) of animals that became immobilized with one dart
      (8.7 +/- 3.2 min, 7.3 +/- 3.9 min) and recovery times of all animals (3.4 +/- 1.5
      min, 3.9 +/- 1.6 min) were not significantly different between MK and MAA groups,
      respectively. Both MK and MAA groups experienced severe hypoxemia (PaO2 42 +/- 9
      mmHg, 40 +/- 10 mmHg, respectively). PaCO2 was significantly higher ( P = 0.0248)
      in the MK group (median 54 mmHg) than the MAA group (median 48 mmHg) with a trend
      towards lower pH (7.40 vs 7.42, respectively, P = 0.07). Initially, MK animals
      had higher heart rates than MAA animals (median 49 vs 40 beats/min), which
      decreased over time. In bighorn sheep, both MK and MAA produced reliable,
      reversible immobilization with smooth inductions and recoveries. However, less
      respiratory depression was seen with MAA than MK.

PMID- 30212347
TI  - AAZV PUBLICATIONS AVAILABLE.

PMID- 30212346
TI  - DIAGNOSTIC PERFORMANCE OF INFLAMMATORY MARKERS IN GOPHER TORTOISES ( GOPHERUS
      POLYPHEMUS).
AB  - The lack of sensitive and specific markers of inflammation poses a diagnostic
      challenge in sick or injured reptile patients. The objective of this study was to
      investigate the diagnostic performance of blood analytes associated with
      inflammation in healthy ( n = 24) and sick ( n = 38) gopher tortoises ( Gopherus
      polyphemus). Receiver operating characteristic analysis identified the following
      as the best-performing diagnostic tests: erythrocyte sedimentation rate (area
      under the curve [AUC] = 0.812; 95% confidence interval [CI] = 0.693, 0.900),
      absolute mature heterophils (AUC = 0.771; 95% CI = 0.646, 0.869), total
      leukocytes (AUC = 0.767; 95% CI = 0.642, 0.866), lactate (AUC = 0.766; 95% CI =
      0.641, 0.864), and absolute immature heterophils (AUC = 0.755; 95% CI = 0.628,
      0.856). These results support the clinical application of additional tools for
      the diagnosis and monitoring of inflammatory disease in gopher tortoises.
      Clinicians may consider adding erythrocyte sedimentation rate and lactate to the
      minimum database for this species.

PMID- 30212348
TI  - ANATOMY, HISTOLOGY, AND DIAGNOSTIC IMAGING OF THE REPRODUCTIVE TRACT OF MALE
      AARDVARK ( ORYCTEROPUS AFER).
AB  - The reproductive tracts of three captive male aardvark ( Orycteropus afer) were
      evaluated to characterize the gross and histological anatomy, with correlations
      to ultrasonographic and computed tomographic imaging. Observations were made from
      a reproductive tract examined at necropsy, with subsequent evaluation of tissues
      histologically. Two living specimens were evaluated via ultrasonography with a 10
      MHz linear transducer. One living animal was also evaluated via computed
      tomography. Prominent external scent glands were present at the base of the
      prepuce. Testicles were present internally at the level of the inguinal canal and
      capable of sliding into a subcutaneous position. Accessory sex glands consisted
      of seminal vesicles, prostate gland, and bulbourethral glands, with histological
      characteristics similar to other species. Ultrasonography was an effective tool
      for evaluation of internal and external reproductive structures, while the
      usefulness of computed tomography was limited in the evaluation of pelvic organs
      due to artifact from nearby bony structures. While a larger study population is
      desirable, this report provides an important comparative anatomical reference and
      will help improve the clinical management and care of this species.

PMID- 30212350
TI  - PLASMA CONCENTRATIONS OF VITAMIN A1, B1, D3, AND E IN HUMBOLDT PENGUINS (
      SPHENISCUS HUMBOLDTI) BEFORE AND AFTER DIETARY VITAMIN SUPPLEMENTATION OF THEIR
      FISH DIET.
AB  - In a practical feeding trial at Ouwehand Zoo, plasma concentrations of vitamin
      A1, calcidiol (D3), alpha-tocopherol (E), and B1 in 17 Humboldt penguins (
      Spheniscus humboldti) were measured before and after supplementation to gain
      insight into the effect of supplementing these vitamins in animals being fed
      thawed frozen-fish diets. None of the penguins received vitamin supplements for
      at least 6 mo before the supplementation trial, which was conducted prior to
      their normal nesting and molting period. During the trial period, eight penguins
      received daily vitamin A1, D3, tocopheryl acetate, and B1 supplementation placed
      in their fish immediately prior to feeding and nine control penguins received no
      supplementation. Concentrations of vitamins A1, D3, alpha-tocopherol, and B1 were
      also measured in the thawed ready-to-feed fish. Concentrations of vitamins B1 and
      alpha-tocopherol were below the Association of Zoos and Aquariums (AZA)
      recommendations for penguin diets, while concentrations of vitamins A1 and D3
      were far above AZA recommendations. At the start of the study and after 70 days
      of supplementation, plasma concentrations were determined for these vitamins.
      Vitamin B1 concentrations in plasma increased significantly ( P < 0.05) between
      Day 0 (mean 39.9 MUg/L) and day 70 (mean 160.5 MUg/L) in the supplemented group.
      Plasma vitamin D3 and alpha-tocopherol did not show a significant change. Vitamin
      A1 levels in the supplemented group decreased significantly from 1.65 mg/L on day
      0 to 1.4 mg/L on day 70. In the control group no significant changes were
      observed. The results of the study support the necessity of supplementing vitamin
      B1 in penguins fed thawed frozen fish. Depletion of vitamin A and E
      concentrations in frozen food fish over time support recommendations to regularly
      measure vitamin concentrations in different batches of frozen fish.

PMID- 30212351
TI  - SQUAMOUS CELL CARCINOMAS WITH PULMONARY METASTASIS AND ENDOCARDIOSIS IN THE
      SIBERIAN CHIPMUNK ( EUTAMIAS SIBIRICUS): TWO NECROPSY CASES.
AB  - Reports of neoplastic diseases in the Siberian chipmunk ( Eutamias sibiricus) are
      limited. The authors describe herein two necropsy cases of Siberian chipmunks
      with squamous cell carcinoma; both of which showed self-biting behaviors on
      presentation to the clinician. In both cases, the neoplasms comprised trabeculae
      and islands of polyhedral cells, supported by moderate amounts of fibrous stroma.
      Anisocytosis and anisokaryosis were moderate to prominent. Neoplastic cells were
      occasionally keratinized, with a keratin pearl formation. In one case, valvular
      endocardiosis of the left and right atrioventricular valves with secondary
      pulmonary and hepatic lesions was incidentally diagnosed. This report provides
      the first documentation of squamous cell carcinoma and endocardiosis in the
      Siberian chipmunk.

PMID- 30212352
TI  - REVIEW OF MORTALITY AND EFFECTIVENESS OF NEONATAL TREATMENT IN CAPTIVE ATTWATER'S
      PRAIRIE CHICKENS ( TYMPANUCHUS CUPIDO ATTWATERI).
AB  - A retrospective study of mortality and neonatal treatment for 975 Attwater's
      prairie chickens ( Tympanuchus cupido attwateri) was conducted from 2009-2015.
      Gross necropsy, histopathology, and medical records for chicks less than 8 wk of
      age at the Houston Zoo were reviewed and summarized. The total mortality rate was
      36% ( n = 352). Yolk sac infection was the most common cause of death (21%; n =
      73) followed by maladaptation (19%; n = 68), musculoskeletal abnormalities (19%;
      n = 66), necrotic enteritis (13%; n = 44), and mucoid enteritis (11%; n = 39).
      Gavage feeding of a highly digestible formula was associated with a higher
      proportion of necrotic enteritis and a reduced occurrence of both mucoid
      enteritis and maladaptation. Meloxicam administration had a significantly reduced
      incidence of mucoid enteritis. Survival past 10 days of age, prevention of
      neonatal bacterial infection, and supportive treatment with meloxicam are
      important factors to increase chick survival and improve captive breeding success
      for Attwater's prairie chickens. Gavage feeding of a diet low in digestible
      carbohydrates has the potential for reducing disease due to necrotic enteritis in
      this species.

PMID- 30212353
TI  - EVALUATION OF THE OPHTHALMIC DISEASE AND HISTOPATHOLOGIC EFFECTS DUE TO THE
      OCULAR TREMATODE PHILOPHTHALMUS ZALOPHI ON JUVENILE GALAPAGOS SEA LIONS (
      ZALOPHUS WOLLEBAEKI).
AB  - The Galapagos sea lion ( Zalophus wollebaeki) is an otariid species endemic to
      the Galapagos archipelago and is currently listed as endangered. The ocular
      trematode Philophthalmus zalophi was recently reported to affect the survival of
      juvenile Galapagos sea lions on Santa Cruz Island, resulting in marked ophthalmic
      changes. This study evaluated the ophthalmic disease and histopathologic effects
      of P. zalophi on juvenile Galapagos sea lions in the largest rookery located on
      San Cristobal Island. Twenty juvenile Galapagos sea lions (10 male and 10 female)
      were evaluated among five sites in the rookery El Malecon. Ophthalmic
      examination, including fluorescein staining and evaluation of the adnexa, cornea,
      and sclera, were performed on each eye. The presence, number, and location of
      ocular parasites were determined, and parasites were collected for
      identification. Conjunctival biopsy was performed on 11 animals: 2 that lacked
      parasites and gross lesions and 9 with both parasites and gross lesions. All
      parasites collected were confirmed as P. zalophi and identified in 80% (16/20) of
      the study animals and 70% (28/40) of the examined eyes. Philophthalmus zalophi
      was most frequently found attached to the nictitating membrane but also located
      on the palpebral conjunctiva or cornea. The most common clinical signs were
      varying degrees of conjunctival hyperemia (28/40 eyes), most frequently of the
      nictitating membrane and mucoid ocular discharge (12/40 eyes). The number of
      parasites was significantly associated with the degree of conjunctival hyperemia
      ( P < 0.001). Histopathology of conjunctival biopsies revealed organized lymphoid
      follicles and lymphoplasmacytic infiltrates. The histopathologic changes and
      gross lesions were likely due to the parasite's attachment to the conjunctiva.
      This study provides additional details of P. zalophi infection in juvenile
      Galapagos sea lions. Further research is warranted to detail the life cycle of
      this parasite, transmission to sea lions, and potential treatment protocols.

PMID- 30212354
TI  - REPRODUCTIVE HORMONE PATTERNS IN MALE AND FEMALE COWNOSE RAYS ( RHINOPTERA
      BONASUS) IN AN AQUARIUM SETTING AND CORRELATION TO ULTRASONOGRAPHIC STAGING.
AB  - Reproductive management of cownose rays ( Rhinoptera bonasus) under professional
      care plays an important role in conservation of the species, but hormone and
      ultrasonographic analyses of their 12-mo reproductive cycle have not been
      documented previously. Plasma reproductive hormone concentrations (17B-estradiol,
      progesterone, testosterone, and androstenedione) were measured monthly via
      radioimmunoassay for 1 yr in an aquarium-managed population of adult females ( n
      = 15) and males ( n = 5). Ultrasounds of the uterus were performed each month at
      the time of sample collection to identify gestation stage (0-5) based on a
      previously developed in-house staging system. Stages were correlated to hormone
      concentrations to track progression through pregnancy. Thirteen females were
      reproductively active, and each produced one pup in March-June, similar to timing
      for free-ranging populations. Female estradiol increased steadily throughout
      gestation from stages 0 to 5, while progesterone, testosterone, and
      androstenedione were increased only in early gestation (stages 1 and 2). Unlike
      month of year, gestation stage strongly predicted hormone concentration, but
      specific values to predict parturition date were not identified. Male
      testosterone and progesterone were higher in March-June (mating season) than July
      January, while estradiol and androstenedione did not exhibit a seasonal pattern.
      Aquarium-managed cownose rays have similar reproductive patterns to what is
      reported in wild populations. Ultrasonographic monitoring with serial hormone
      analysis and accurate mating records will provide the most useful information for
      managing a reproductive population of cownose rays in an aquarium setting.

PMID- 30212355
TI  - EFFECTS OF GONADOTROPIN-RELEASING HORMONE ANTAGONIST DEGARELIX ON MUSTH AND SERUM
      TESTOSTERONE CONCENTRATIONS IN ASIAN ELEPHANTS ( ELEPHAS MAXIMUS).
AB  - Two male Asian elephants (bulls 1 and 2) in musth were subcutaneously injected
      with a long-acting gonadotropin-releasing hormone (GnRH) antagonist, degarelix
      acetate (240 MUg/kg; total dose of 960 mg). Musth behavior (MB) and temporal
      gland secretions (TGS) were monitored and serum testosterone concentrations were
      determined. In bull 1, MB and TGS ceased on day 1 and reappeared 5.5 mo after the
      treatment (day 0). During the subsequent musth cycle, MB and TGS ceased on day 1
      and did not appear for 4 mo. In bull 2, MB and TGS ceased at day 7 after the
      treatment. Musth behavior and TGS recurred on Day 11 and continued for 1 wk, then
      disappeared for 8 mo. Serum testosterone concentrations decreased ( P < 0.05) in
      all occasions from day 0 (29.8 +/- 15.8 ng/ml; mean +/- SEM) to day 1 (2.2 +/-
      1.1 ng/ml), suggesting a sudden drop in circulating testosterone in musth
      elephants after the GnRH-antagonist treatment.

PMID- 30212356
TI  - PHARMACOKINETICS OF ORAL GABAPENTIN IN CARIBBEAN FLAMINGOS ( PHOENICOPTERUS RUBER
      RUBER).
AB  - Gabapentin is a first-line treatment for neuropathic pain and adjunct
      anticonvulsant medication in humans and other species. Gabapentin may have
      advantages over other analgesics because of its broad therapeutic range with
      limited adverse effects and wide availability as an oral formulation. This study
      determined the pharmacokinetics of gabapentin in Caribbean flamingos (
      Phoenicopterus ruber ruber) after a single-dose oral administration of either 15
      mg/kg ( n = 6) or 25 mg/kg ( n = 6). Plasma gabapentin concentrations were
      determined using liquid chromatography with mass spectrometry, and
      pharmacokinetic analysis was performed using noncompartmental methods.
      Respectively for the 15 mg/kg and 25 mg/kg dose, mean peak plasma concentration (
      Cmax) was (mean +/- pseudo SD) 13.23 +/- 1.47 and 24.48 +/- 5.81 MUg/ml; mean
      time to peak plasma concentration ( Tmax) was 0.50 +/- 0.24 and 0.56 +/- 0.28 hr;
      mean area under the curve (AUC) was 76.0 +/- 26.3 and 114.7 +/- 27.5 hr.MUg/ml;
      and mean terminal half-life ( T1/2) was 3.39 +/- 0.90 and 4.46 +/- 1.12 hr. Based
      on the results of this study, gabapentin dosed at 25 mg/kg orally in most
      Caribbean flamingos is likely to maintain plasma concentrations above the
      therapeutic range established for humans for approximately 12 hr.

PMID- 30212357
TI  - RETROSPECTIVE ANALYSIS AND VALIDATION OF SERUM SYMMETRIC DIMETHYLARGININE (SDMA)
      CONCENTRATIONS IN CHEETAHS ( ACINONYX JUBATUS).
AB  - Kidney disease is common among captive cheetahs ( Acinonyx jubatus). Serum
      creatinine is the most common measurement to estimate glomerular filtration rate
      (GFR) because of the ease of its clinical use, but it is a crude estimate that
      only increases after significant disease is already present and is affected by
      extrarenal factors. Symmetric dimethylarginine (SDMA) is a renal biomarker in
      humans, dogs, and cats that correlates with serum creatinine and GFR and appears
      to be an earlier and more specific biomarker for kidney disease. Ninety-two
      banked serum samples from 11 cheetahs housed at the Oklahoma City Zoo from 1992
      to 2012 were retrospectively analyzed. Histopathology results were available for
      10/11 cheetahs, and all 10 had histologic renal lesions. General categories of
      renal lesions included glomerulosclerosis (7/10; 70%), amyloidosis (7/10; 70%),
      inflammatory (9/10; 90%), and oxalate nephrosis (2/10; 20%). SDMA immunoassay and
      mass spectrometry were measured for validation and compared with creatinine to
      assess for correlation. Serum creatinine concentrations were determined by
      enzymatic colorimetric methods. SDMA immunoassay was validated in cheetahs and
      correlated well with serum creatinine ( R2=0.687; P < 0.0001). SDMA and serum
      creatinine measured from freeze-thawed stored samples show high correlation in
      individual cheetahs ( R2 = 0.972; P < 0.0001). These data support that SDMA could
      be a promising renal biomarker in cheetahs. Further research is warranted to
      investigate whether SDMA might be an earlier indicator of kidney disease in
      cheetahs and whether this assay can be extended to other nondomestic carnivores.

PMID- 30212358
TI  - ARTIFICIAL ULTRAVIOLET B RADIATION RAISES PLASMA 25-HYDROXYVITAMIN D3
      CONCENTRATIONS IN BURMESE PYTHONS ( PYTHON BIVITTATUS).
AB  - Deficiency of vitamin D can contribute to health complications that present as
      metabolic bone disease. The aim of this small-scale study was to determine if a
      high UVb irradiance would affect an increase in plasma vitamin D3 concentrations
      in Burmese pythons ( Python bivittatus). There have been inconsistent results
      throughout the literature concerning the usefulness of UVb radiation regarding
      vitamin D3 synthesis. Blood samples of four healthy Burmese pythons were taken at
      day 0 and day 310. After the first blood sample was taken, an Arcadia Superzoo T5
      ASZ01 lamp was fitted in the enclosure. For 310 days, the pythons were exposed to
      UVb radiation. Blood plasma vitamin D3 concentrations were considerably higher
      after UVb exposure. This study indicates that a period of 10 mo of UVb exposure
      can result in an increased vitamin D3 status in Burmese pythons. Answering
      whether these elevated levels have health benefits for Burmese pythons (and
      possibly other snake species) requires further studies.

PMID- 30212359
TI  - Retracted: Comparison of DNA Damage and Apoptosis Induced By Silver Nanoparticle
      containing Dressing Materials During Wound Healing.
AB  - The Editor and Publisher regretfully have to retract the following two
      publications due to faulty study design.

PMID- 30212360
TI  - Retracted: Degree of the Hazards of Silver-Containing Dressings on MRSA-Infected
      Wounds in Sprague-Dawley and Streptozotocin-Induced Diabetic Rats.
AB  - The Editor and Publisher regretfully have to retract the following two
      publications due to faulty study design.

PMID- 30212361
TI  - Using Bacterial Fluorescence Imaging and Antimicrobial Stewardship to Guide Wound
      Management Practices: A Case Series.
AB  - The urgent need to eliminate unnecessary use of antibiotics in wound patients has
      been hampered by diagnostic uncertainty and the time required to obtain culture
      results. The authors evaluated bedside use of a handheld bacterial fluorescence
      imaging device for real-time visualization of bacteria within and around wounds,
      used in addition to monitoring of clinical signs and symptoms of infection, in a
      series of 7 patients (5 women, 2 men; age range 57-93 years) with varying
      comorbidities who were referred to the wound ostomy continence clinician for
      wound assessment. When excited by 405-nm violet light, tissues fluoresce green
      (collagens) and bacteria fluoresce red; specialized optical filters reveal these
      colored signals in real time on the device's display screen. Wounds exhibiting
      red fluorescence were presumed to have moderate/heavy bacterial contamination
      (>=104 CFU/g) and were subsequently swabbed. Swabs from the 5 wounds with regions
      of red fluorescence confirmed heavy growth of 1 or more pathogenic bacterial
      species. Images revealing pronounced bacterial fluorescence in 3 patients with
      pressure injuries about to be discharged led to prescription of systemic
      antibiotics and additional patient monitoring. In 2 patients (1 with a skin tear,
      1 with a surgical wound), the absence of bacterial fluorescence prevented
      planned, unwarranted use of systemic antibiotics. Fluorescence images obtained
      bedside during routine wound assessments had a direct effect on antimicrobial
      stewardship practices. Follow-up images demonstrated antibiotic effectiveness
      and, in some instances, led to reduced antibiotic courses and duration. This case
      series demonstrates the potential use for real-time information on bacterial
      presence obtained via bacterial fluorescence imaging to guide evidence-based
      deployment of antibiotics and prevent unnecessary use. Additional studies to
      optimize the diagnostic potential and randomized controlled studies to examine
      the effect of this technique on antibiotic usage, antimicrobial stewardship
      practices, and wound outcomes are warranted.

PMID- 30212362
TI  - The Role of Topical Estrogen, Phenytoin, and Silver Sulfadiazine in Time to Wound
      Healing in Rats.
AB  - Many recent studies have focused on the potential role of topical agents in the
      wound healing process. To compare the time to healing of full-thickness wounds
      treated with topical estrogen, phenytoin, or silver sulfadiazine (SSD), an in
      vivo study was conducted using 32 male Wistar rats. Animals were housed
      individually in standard cages in similar environmental conditions, and a single,
      circular (4 mm in diameter), full-thickness skin wound was created on the dorsum
      of each rat. Animals were randomly divided into 4 groups of 8 rats each and
      treated with topical phenytoin, SSD, estrogen cream, or no treatment/control.
      Each wound was measured and examined daily until healing, defined as complete
      reepithelialization and closure of the wound. Group mean healing times were
      calculated, and Tukey's multiple comparison test was used to compare these data.
      Average times to healing were 11 days in estrogen group, 10 days in phenytoin
      group, 7.62 days in SSD group, and 11.87 days in control group. Wound healing was
      significantly faster in the SSD compared to control (P <.01) and the estrogen
      group (P <.01). No other differences were statistically significant. Further
      studies, especially randomized clinical trials on human beings with larger sample
      sizes, are recommended to elucidate if these topical agents affect wound
      outcomes.

PMID- 30212363
TI  - Assessment of Prelicensure Undergraduate Baccalaureate Nursing Students: Ostomy
      Knowledge, Skill Experiences, and Confidence in Care.
AB  - Care of the patient with an ostomy is included in the curriculum of prelicensure
      nursing programs, but no studies examining student nurses' knowledge about stoma
      care have been published. The purpose of this project was to examine the ostomy
      knowledge, experiences, and confidence of nursing students in order to assess and
      improve the curriculum. At the end of the fall 2016 semester, students enrolled
      in 3 separate nursing courses in an undergraduate program were asked to
      participate in a project to examine students' ostomy knowledge, their
      experiences, and their confidence in providing care. This project was undertaken
      to explore the college's ostomy curriculum. Participation was voluntary, and no
      student who was willing to participate was excluded. Students completed a 50
      question knowledge test, answered questions about the frequency of performing
      ostomy-related skills, and rated their confidence in providing ostomy care.
      Responses were examined with descriptive and inferential statistics. Of 189
      possible participants, 138 completed the questionnaires and included mostly women
      (113, 81.9%); participant mean age was 27.26 +/- 6.22 years. The mean number of
      correct knowledge responses was 35.66 (71.32%); 66 participants (47.8%) reported
      no experience caring for a patient with an ostomy. The most common skills
      performed in clinical rotations were emptying (49) and changing (24) the pouch. A
      scale of 1 to 5 was used to evaluate 6 confidence items, with students having a
      mean confidence score of 19.54 +/- 5.20. They had the most confidence in their
      ability to empty a pouch and to size and fit the pouching and the least
      confidence in teaching and community resources. Confidence was related to the
      number of skills performed in the lab (r = .32; P <.001), the number of skills
      performed in clinical practice (r = .38; P <.001), and ostomy knowledge scores (r
      = .23; P <.007). Total correct knowledge scores did not differ significantly by
      year in the educational program. Based on the results of this survey, it was
      concluded that students had a beginning knowledge about ostomy care and very
      limited clinical experience, yet confidence in providing ostomy care was high.
      Curriculum adjustments were implemented, including strategies for increasing
      ostomy knowledge, opportunities to provide care, and confidence; these need
      further investigation in prelicensure undergraduate nursing programs. The effect
      of curriculum adjustments remains to be evaluated.

PMID- 30212364
TI  - Is PASH Syndrome a Biofilm Disease?: A Case Series and Review of the Literature.
AB  - INTRODUCTION: When occurring together, pyoderma gangrenosum, severe acne, and
      hidradenitis suppurativa have been described as PASH syndrome. Due to the chronic
      autoinflammatory state existing in affected patients, PASH syndrome has been
      attributed to the dysregulation of wound healing. CASE REPORTS: Two cases are
      presented that demonstrate the paradigmatic clinical features of PASH syndrome
      and its potential link as an expanding spectrum of bacterial biofilm disorder.
      CONCLUSIONS: As reported herein, based on biofilm's clinical presentation and
      resistance to proper wound healing, it could serve as the common denominator and
      may redirect clinicians' treatment pathways in the near future.

PMID- 30212365
TI  - Efficacy of Dehydrated Human Amniotic Membrane Allograft for the Treatment of
      Severe Extravasation Injuries in Preterm Neonates.
AB  - INTRODUCTION: A peripheral intravenous (PIV) catheter is placed in 60% to 70% of
      neonatal intensive care unit (NICU) infants. Extravasation injuries occur in 18%
      to 33%, with 70% in neonates < 27 weeks of gestational age. Despite such frequent
      use of PIV therapy, evidence on best practice, injury prevention, management, and
      treatment of extravasations is lacking. OBJECTIVE: This case series of 4 neonatal
      patients describes the experience and efficacy of using a dehydrated human
      amniotic membrane allograft (dHAMA) in the treatment of severe extravasation
      injuries. MATERIALS AND METHODS: The 4 preterm, critically ill neonates, all with
      stage 4 extravasations, were treated with 1 to 2 applications of the dHAMA to
      facilitate the repair process. Prior to treatments, standard of care included
      either enzymatic (collagenase ointment) or autolytic debridement (active
      Leptospermum honey) followed by mechanical debridement prior to allograft
      placement. RESULTS: The 4 full-thickness wounds exhibited recalcitrant healing.
      The dHAMA invigorated the wounds after standard management failed to induce
      repair. Application was easy and follow-up care was minimal. All wounds healed
      without contractures and with minimal soft scars and normal pigmentation at the 1
      to 2-month follow-up visits. CONCLUSIONS: The dHAMA proved to be an effective,
      safe, and easy-to-apply treatment in this case series, leading to regeneration
      and healing of deep neonatal wounds associated with extravasations.

PMID- 30212366
TI  - The Role of Negative Pressure Wound Therapy in Managing Chinese Patients With
      Wound-derived Acute Severe Illness.
AB  - INTRODUCTION: Resulting mostly from major injury or infection, severe acute
      wounds are often accompanied by septic shock or multiple organ failure and
      associated with high disability and mortality rates. In managing Chinese patients
      with wound-derived acute severe illnesses, salvage treatment in the emergency
      department has traditionally prioritized life support and protection of vital
      organs before wound repair. OBJECTIVE: This retrospective review evaluated the
      outcomes of patients with wound-derived acute severe illness who were treated
      with a new salvage protocol that combined proactive wound care with simultaneous
      life-support measures. MATERIALS AND METHODS: Records from 2011 to 2013 at Peking
      Union Medical College Hospital (PUMCH) in Beijing, China, were reviewed to
      identify patients with wound-derived acute severe illness treated with the new
      protocol. The plastic surgery department, emergency department, and intensive
      care unit developed the protocol, which included proactive wound treatment with
      negative pressure wound therapy (NPWT), interdepartmental cooperation, and
      comprehensive patient treatment. RESULTS: Fifty-six patients were managed with
      the new protocol. At presentation, all patients were in septic shock and 29 of 56
      (51.8%) required mechanical ventilation. Of the treated patients, 21 (37.5%)
      fully recovered and 29 (51.8%) improved sufficiently enough for transfer to a
      general ward. Six patients (10.7%) died of causes unrelated to NPWT. CONCLUSIONS:
      At PUMCH, the new collaborative salvage protocol with proactive use of NPWT with
      simultaneous life- support methods resulted in greater therapeutic effects than
      traditional salvage treatment could offer.

PMID- 30212367
TI  - Surgical Site Infections Related to ESBL Pathogens Post Colon Surgery.

PMID- 30212368
TI  - Two Cases of Severe Erosive Pustular Dermatosis Mimicking Infection.
AB  - INTRODUCTION: Erosive pustular dermatosis of the scalp (EPDS) is a noninfectious
      inflammatory disorder characterized by pustules, erosions, ulcerations, and
      crusted erythematous plaques that is often associated with mechanical or chemical
      trauma. While its appearance may mimic infection, its etiology is thought to have
      an autoimmune component based on responsiveness to immunomodulators. CASE REPORT:
      Herein, the authors present 2 cases of EPDS that were initially treated as
      primary infections. In both cases, the wounds did not respond to antimicrobial
      treatment and led to severe ulceration, exposing cranial bone. Both wounds
      improved with topical corticosteroid therapy. CONCLUSIONS: These cases represent
      the importance of considering topical steroid treatment and a diagnosis of EPDS
      after debridement for purulent scalp ulcers.

PMID- 30212369
TI  - A Patient-centered Remote Therapy Monitoring Program Focusing on Increased
      Adherence to Wound Therapy: A Large Cohort Study.
AB  - OBJECTIVE: This retrospective study of 510 patients receiving negative pressure
      wound therapy (NPWT) in a home care setting examines the relationship between
      remote therapy monitoring (RTM) and patient adherence, as well as determines the
      impact of patient adherence on wound progression. MATERIALS AND METHODS:
      Adherence to treatment was continuously monitored via RTM, and patients with
      therapy usage < 16 hours in 1 day received an adherence call. Repeated failures
      to reach a noncompliant patient led to an escalation call to the caregiver to
      discuss treatment. Wound volume and surface area were collected to determine the
      rate of wound size reduction. RESULTS: A total of 3261 calls were made with an
      average of 6.4 calls per patient. Among the 510 patients, 98% received a welcome
      call, 87% received at least 1 call due to low adherence, and 30% received an
      escalation call. The day following an adherence call, 73.5% of patients increased
      therapy use. As adherence to NPWT increased (< 60% to 90%-100% therapy use),
      there was an increase in the daily reduction rate in wound volume (1.42% to
      2.23%) and surface area (0.86% to 1.45%). CONCLUSIONS: The data suggest RTM can
      be used to influence patient behavior, and there may be a potential relationship
      between patient behavior and wound healing outcomes. Additional studies are
      needed to elucidate the relationship between RTM and wound outcomes.

PMID- 30212370
TI  - Implantable Nanomedical Scaffold Facilitates Healing of Chronic Lower Extremity
      Wounds.
AB  - BACKGROUND: Chronic, nonhealing wounds are a growing health care problem in the
      United States, affecting more than 6.5 million patients annually. OBJECTIVE: This
      retrospective study evaluates the clinical efficacy and utility of an implantable
      nanomedical scaffold in the treatment of chronic, nonhealing lower extremity
      wounds in patients with multiple comorbidities. MATERIALS AND METHODS: Data from
      patients with chronic wounds that had persisted for >= 4 weeks and were
      unresponsive to existing advanced wound care modalities were included in the
      study. Wounds received the implantable nanomedical scaffold weekly, or as deemed
      appropriate, for up to 12 weeks based on physician assessment of wound status.
      RESULTS: A total of 82 wounds were included in this study; wound types consisted
      of 34 diabetic foot ulcers, 34 venous leg ulcers, and 14 other wounds. Overall,
      treated wounds demonstrated progressive and sustained wound area reduction over
      the course of treatment, with 85% achieving complete closure at 12 weeks.
      CONCLUSIONS: The implantable nanomedical scaffold proved to be an effective
      alternative to existing wound matrices capable of supporting the natural wound
      healing process and may provide significant benefits as part of the treatment
      algorithm for challenging chronic wounds.

PMID- 30212371
TI  - Extract of Berula angustifolia (L.) Mertens Enhances Wound Healing in
      Streptozotocin-induced Diabetic Rats.
AB  - INTRODUCTION: Diabetes-impaired wound healing and other tissue abnormalities are
      considered to be a major concern. OBJECTIVE: The aim of this study is to assess
      the wound healing activity of the methanolic extracts of Berula angustifolia
      leaves. MATERIALS AND METHODS: Seven- week-old male Wistar rats with diabetes
      induced by streptozotocin injection were randomized into 5 groups of 6 rats based
      on allocated treatment. Wounds were created by an excision-based or incision
      based wound model. For wound healing activity, the extracts were applied
      topically in the form of ointment and compared with the control groups. The
      healing of the wound was assessed based on excision, incision, hydroxyproline
      estimation, biomechanical, and biochemical studies. RESULTS: The healing rate of
      the extract-treated groups was significantly different compared with the control
      group (P < .05). Hydroxyproline contents increased significantly in the extract
      treated groups (P < .05). There were significant differences in the extract
      treated versus nonextract-treated groups, particularly in terms of cellular
      infiltration, acute hemorrhage, congestion, edema, collagen production and
      density, reepithelialization, and neovascularization. CONCLUSIONS: The methanolic
      extract of B angustifolia enhances wound healing activity significantly in both
      studied wound models. From this animal study, enhanced wound contraction,
      decreased epithelialization time, increased hydroxyproline content, improved
      mechanical indices, histological characteristics, and biochemical studies suggest
      the extract of B angustifolia leaves may have therapeutic benefits in diabetes
      impaired wound healing.

PMID- 30212372
TI  - Pressure Injury Prevention Practices in the Intensive Care Unit: Real-world Data
      Captured by a Wearable Patient Sensor.
AB  - BACKGROUND: Compliance with turning protocols in the intensive care unit (ICU) is
      low; however, little is known about the quality of turning, such as turn angle
      magnitude or depressurization time. Wearable sensors are now available that
      provide insight into care practices. OBJECTIVE: This secondary descriptive study
      describes the turning practices of nurses from 2 ICUs at an academic medical
      center among consecutive ICU patients. MATERIALS AND METHODS: A wearable patient
      sensor was applied to patients on hospital admission. The sensor continuously
      recorded position data but was not visible to staff. A qualified turn was one
      that reached > 20 degrees  angle and was held for 1 minute after turning. The
      institution's clinical research repository provided clinical data. RESULTS: A
      total of 555 patients were analyzed over a 5-month period (September 2015-January
      2016); 44 870 hours of monitoring data (x- = 73 hours +/- 97/patient) and 27 566
      individual turns were recorded. Compliant time was recorded as 54%, with 39% of
      observed turns reaching the minimum angle threshold and 38% of patients remaining
      in place for > 15 minutes (depressurization). Turn magnitude was similar for
      medical and surgical patients. Factors associated with lower compliant time
      included male sex, high body mass index, and low Braden score. Patients were
      supine for 72% of the observed time. CONCLUSIONS: The investigators found
      dynamically measured turning frequency, turn magnitude, and tissue
      depressurization time to be suboptimal. This study highlights the need to
      reinforce best practices related to preventive turning and to consider staff and
      patient factors when developing individualized turn protocols.

PMID- 30212373
TI  - Soft Tissue Coverage of Complex Periprosthetic Defects in Patients With Total
      Knee Arthroplasty: Analysis of Factors That Influence Reconstructive and
      Functional Outcomes.
AB  - INTRODUCTION: Wound breakdown following total knee arthroplasty (TKA) increases
      the risk of device exposure, infection, and major amputation. Although a variety
      of options to facilitate coverage of compromised knee joint prostheses exist, the
      relative safety, efficacy, and functional impact of each has not been determined.
      OBJECTIVE: This study aims to identify those perioperative factors that influence
      reconstructive and functional outcomes in patients with periprosthetic TKA
      defects. MATERIALS AND METHODS: A 5-year retrospective review of outcomes
      following surgical management of TKA wounds was undertaken. Data pertaining to
      the timing of presentation, type and frequency of operative interventions, rates
      of implant/limb salvage, ambulatory status, visual analogue scores (VAS) for
      pain, and complications were collected. RESULTS: Thirty patients were identified
      during the study period with a mean follow-up of 20 months. Rates of limb salvage
      (66.7% vs. 91.7% vs. 75% vs. 0%, P < .001) and postoperative ambulation (100% vs.
      83.3% vs. 75% vs. 54.5%, P = .036) were significantly different between patients
      who underwent primary closure, local muscle flap coverage, free tissue transfer
      coverage, and above-the-knee amputation, respectively. The number of debridements
      prior to definitive closure did not significantly influence rates of limb salvage
      (P = .21). Active tobacco use (odds ratio [OR], 4; 95% confidence interval [CI],
      1.13-14.2; P = .03) and time to initial presentation from the index joint
      replacement (OR, 0.99; 95% CI, 0.9-1.0; P = .04) adversely impacted device
      salvage. Both of these factors similarly influenced the overall likelihood of
      limb salvage (OR, 6.5; 95% CI, 1.5-28.8; P = .01; OR, 0.99; 95% CI, 0.99-1.0; P =
      .04). The VAS scores were not significantly different between index closure types
      (P = .77) but were significantly lower for patients who required < 10
      debridements prior to definitive closure (P = .02). CONCLUSIONS: Early
      intervention with limited-frequency, and thorough debridement and prompt soft
      tissue coverage optimizes the chances of functional limb salvage in patients with
      complex periprosthetic TKA wounds. These findings may inform practice patterns
      and surgical treatment of patients presenting with compromised TKA and suggest
      that early involvement by reconstructive surgeons should be advocated to optimize
      reconstructive and functional outcomes in this difficult patient population.

PMID- 30212374
TI  - Negative Pressure Wound Therapy of Open Abdomen and Definitive Closure Techniques
      After Decompressive Laparotomy: A Single-center Observational Prospective Study.
AB  - INTRODUCTION: Open abdomen is a concept that was developed especially in relation
      to abdominal compartment syndrome (ACS). OBJECTIVE: This study presents the
      evolution and complications related to the management of the open abdomen after
      decompressive laparotomy, using a standardized method based on negative pressure
      wound therapy (NPWT). MATERIALS AND METHODS: This observational prospective study
      conducted over a 9-month period included 19 patients who underwent decompressive
      laparotomies for ACS. The triggering conditions were peritonitis, infected and
      noninfected acute pancreatitis, ileus, and trauma. Temporary abdominal closure
      was performed using NPWT and the final closure by primary suture or dual mesh.
      Intra-abdominal pressure was permanently and indirectly monitored transvesically.
      RESULTS: After decompressive laparotomy, the intra-abdominal pressure decreased
      significantly (P < .001) compared with the value preoperatively (41.4 mm Hg to
      15.3 mm Hg). Mortality was 21.2%, with higher rates for acute pancreatitis (odds
      ratio [OR] = 3.75) and trauma (OR = 1.25) due to the severity of the primary
      illness. The final closure was performed after 11.7 days, and primary closure was
      possible in 4 cases. CONCLUSIONS: Decompressive laparotomy significantly reduced
      intra-abdominal pressure for ACS, improving the prognosis.

PMID- 30212375
TI  - Insulated Offloading Provides Offloading Protection and Enhanced Skin Perfusion.
AB  - INTRODUCTION: Locally and neurally mediated vasodilation of the cutaneous
      vasculature has been shown to occur in response to locally and systemically
      applied heat stresses. The resultant shunting of blood to the periphery can be
      upwards of 7 L/min to 8 L/min when profound heat stresses are applied. The
      increased cutaneous circulation from local heat stress may benefit extremities
      afflicted with a wound or area of compromised arterial supply. Insulating the
      extremity also may increase local cutaneous perfusion. OBJECTIVE: This study aims
      to determine if increased local warmth from an insulated offloading boot or mitt
      (designed to protect an extremity from trauma, offload the extremity to prevent
      pressure ulcers, and insulate the extremity to minimize heat loss) also results
      in increased local cutaneous perfusion using indocyanine green fluorescence
      angiography (ICGFA). MATERIALS AND METHODS: Nine patients from an outpatient
      wound care clinic with a wound or area of compromised arterial supply on the
      upper or lower extremity were studied prior to and following a minimum of a
      single 60-minute session of insulated offloading boot or mitt use utilizing
      ICGFA. Measurements taken were time to first onset of fluorescence (seconds) and
      ingress and egress rates for the area of concern and the remainder of the area
      imaged. RESULTS: All 9 patients exhibited signs of increased local warmth by a
      mean of 3.1oF while body temperature decreased by a mean of 1.2oF. Local
      cutaneous perfusion increased with a mean change of 1 for the ingress rate to the
      area of concern and a mean change of 0.1 to the remainder of the area imaged.
      Also, ICGFA was able to demonstrate preferential shunting of the increased
      cutaneous perfusion to the site of most need. CONCLUSIONS: These findings suggest
      enhanced skin perfusion may be an additional advantage of insulated offloading
      boot or mitt use.

PMID- 30212376
TI  - Improved performance of GaAsSb/AlGaAs nanowire ensemble Schottky barrier based
      photodetector via in situ annealing.
AB  - In this work, we report on the p-i GaAsSb/AlGaAs nanowires (NWs) ensemble device
      exhibiting good spectral response up to 1.1 MUm with a high responsivity of 311 A
      W-1, an external quantum efficiency of 6.1 * 104%, and a detectivity of 1.9 *
      1010 Jones at 633 nm. The high responsivity of the NWs has been attributed to in
      situ post-growth annealing of GaAsSb axial NWs in the ultra-high vacuum. The
      enabling growth technology is molecular beam epitaxy for the Ga-assisted
      epitaxial growth of these NWs on Si (111) substrates. Room temperature Raman
      spectra, as well as temperature dependent micro-photoluminescence peak analysis
      indicated suppression of band tail states and non-radiative channels due to
      annealing. A similar improvement in in situ annealed p-i GaAsSb NW ensemble with
      an AlGaAs passivating shell was inferred from a reduction in the Schottky barrier
      height as well as the NW resistance compared to the as-grown NW ensemble. These
      results demonstrate in situ annealing of nanowires to be an effective pathway for
      improving the optoelectronic properties of the NWs and the device thereof.

PMID- 30212377
TI  - V-Mart, a Virtual Reality Grocery Store: A Focus Group Study of a Promising
      Intervention for Mild Traumatic Brain Injury and Post-Traumatic Stress Disorder.
AB  - OBJECTIVE: This study examined the potential usability, relevance, and
      acceptability of V-Mart, a virtual reality grocery store as an assessment and
      intervention tool for veterans with mild traumatic brain injury (mTBI). DESIGN:
      Six focus groups were conducted over a two-year period to assess perceptions from
      three key stakeholders: therapists, veterans with neither mTBI nor PTSD, and
      veterans with mTBI with or without PTSD (mTBI/PTSD). The System Usability Scale
      (SUS) was applied as an objective measure of usability. Transcripts from the six
      focus groups were subjected to thematic analyses using the constant, comparative
      method. RESULTS: The focus groups indicated that V-Mart was perceived as highly
      usable, relevant, and acceptable. Early technical problems were resolved
      satisfactorily. Therapists indicated that they would use an application such as V
      Mart if it were available. The veterans with neither mTBI nor PTSD felt it was
      realistic and likely to be useful, as did the veterans with mTBI/PTSD. SUS mean
      follow-up scores ranged from 71.4-86.0, surpassing the threshold for acceptable
      usability in health care settings. CONCLUSIONS: Focus group and SUS data indicate
      that the V-Mart has great potential as an assessment tool and intervention for
      veterans with mTBI/PTSD. Further development and clinical trials are warranted.

PMID- 30212378
TI  - Effects of twitch contraction induced by magnetic stimulation on expression of
      skeletal muscle fibrosis related genes and limited range of motion in rat.
AB  - OBJECTIVE: We examined the effects of twitch contraction induced by lumbar spinal
      root magnetic stimulation on immobilization-induced limited ROM and skeletal
      muscle fibrosis in rat soleus muscle. DESIGN: The groups included male Wistar
      rats (controls), rats with both bilateral ankle joints immobilized with plaster
      casts for 4 weeks (IM), and rats in which twitch contraction of the soleus muscle
      was induced by lumbar magnetic stimulation over the course of 4 weeks of
      immobilization (TC). Group differences in ankle dorsiflexion ROM, collagen
      content as determined by hydroxyproline assay, and the expression of fibrosis
      related genes as determined by RT-PCR (hypoxia inducible factor-1alpha, alpha
      smooth muscle actin, and types I and III collagen) in the soleus muscle were
      examined after the 4-week-long experiment. RESULTS: ROM in the TC group was
      significantly greater than that in the IM group. The hydroxyproline content and
      the expressions of fibrosis-related genes decreased significantly in the TC group
      compared to those in the IM group. No significant differences were seen in the
      expression of TGF-beta mRNA. CONCLUSIONS: These results suggest that twitch
      contraction induced by lumbar spinal root magnetic stimulation may reduce
      immobilization-induced limited ROM and skeletal muscle fibrosis.

PMID- 30212379
TI  - Nestin Expression in Spitzoid Lesions: An Immunohistochemical Characterization
      With Clinical and Dermoscopic Correlations.
AB  - Spindle or epithelioid melanocytic (Spitz) nevi usually affect children or
      adolescents and growth in the face or the lower extremities. Histologically, they
      may show cytoarchitectural atypia and mitotic figures that could represent
      diagnostic pitfalls with malignant melanoma. Atypical spitzoid tumors (AST)
      indicate lesions that microscopically show intermediate characteristics between
      benign nevi and malignant melanoma. Nestin expression has been evaluated in
      benign nevi and malignant melanoma, but no studies on its role in Spitz lesion
      have been elaborated so far. Our results indicate that Nestin could allow to
      discriminate between AST and malignant spiztoid melanoma; the typical dermoscopic
      pattern is also associated with benign nevi in contrast to the atypical pattern
      that accumunates AST and malignant spitzoid melanoma.

PMID- 30212380
TI  - Severe Acute Liver Injury Following Therapeutic Doses of Acetaminophen in a
      Patient With Spinal Muscular Atrophy.

PMID- 30212381
TI  - Myelodysplastic Syndrome After Olaparib Treatment in Heavily Pretreated Ovarian
      Carcinoma.

PMID- 30212382
TI  - Anaplastic Kaposi's Sarcoma of the Adrenal in an HIV-negative Patient With
      Literature Review.
AB  - Kaposi's sarcoma (KS) is a peculiar tumor of viral etiology, with the HHV8
      rhadinovirus playing a fundamental role in its development. Several
      epidemiological categories of KS have been identified, of which the sporadic,
      endemic, iatrogenic, and the epidemic are the main ones. Several histologic
      disease morphologies have been described, such as inflammatory, angiomatous,
      spindle cell, mixed, and the anaplastic (sarcomatous) subtypes. The skin of the
      limbs is most commonly affected, but any other organ or site may be involved.
      Microscopically KS may enter the differential diagnosis with several different
      entities, and for this purpose the immunohistochemical detection of the viral
      latent nuclear antigen-1 (LNA-1) may be crucial. Sporadic KS is usually benign,
      but rarely it may be aggressive. Anaplastic histology heralds an ominous course
      in any clinical context. We report a case of anaplastic retroperitoneal KS,
      occurring in an HIV-negative adult man. This patient presented with a huge left
      suprarenal mass, which was totally resected, and initially diagnosed as
      inflammatory leiomyosarcoma, because of the monomorphic spindle cell tumor
      morphology. After 12 years the tumor recurred locally as an unresectable mass,
      which was biopsied and examined. At the time of recurrence, the histologic slides
      of the primary tumor were reviewed, and the previous diagnosis was changed to
      that of atypical KS. Histologically the recurrent tumor showed both spindle cell
      and epithelioid appearances. Strongly diffuse HHV8/LAN-1 immunopositivity was
      documented in both tumors. The final diagnosis for the entire case was anaplastic
      KS. Then, the patient died in a few months.

PMID- 30212383
TI  - Sex differences in the effectiveness of buprenorphine to decrease rates of
      responding in rhesus monkeys.
AB  - Sex differences in MU-opioid receptor (MOR) agonist-induced antinociception have
      been reported in nonhuman primates. The degree to which MU-opioid receptor
      agonist sex differences in nonhuman primates extend to other behavioral endpoints
      remains unknown. The present study compared the behavioral effects of three MOR
      ligands (fentanyl, buprenorphine, and naltrexone) that varied in efficacy to
      stimulate [S]-GTPgammaS binding (from highest to lowest: fentanyl, buprenorphine,
      and naltrexone) in male and female rhesus monkeys. Male (n=3) and female (n=3)
      monkeys were trained to respond under a fixed-ratio 10 schedule of food
      presentation during daily sessions consisting of multiple components. Once rates
      of responding were stable, cumulative dose-effect functions were determined for
      intramuscular fentanyl (0.00032-0.032 mg/kg), buprenorphine (0.001-1 mg/kg), and
      naltrexone (0.01-0.1 mg/kg). Fentanyl dose-dependently decreased rates of
      responding in both sexes and the corresponding ED50 values were not significantly
      different. Buprenorphine dose-dependently decreased rates of responding in
      females, but not males. Naltrexone did not significantly alter behavior in either
      females or males. Overall, these results suggest that the expression of sex
      differences in MOR pharmacology depends upon both the efficacy of the MOR ligand
      and the behavioral endpoint.

PMID- 30212384
TI  - Spatial learning and flexibility in 129S2/SvHsd and C57BL/6J mouse strains using
      different variants of the Barnes maze.
AB  - Behavioural flexibility is the ability to switch between tasks and strategies
      following a change in rules, and involves intact functioning of the medial
      prefrontal cortex. Impairments of behavioural flexibility have frequently been
      reported in patients with schizophrenia and rodents with disruption/dysfunction
      of the prefrontal cortex. The discovery of a mutation in the disrupted in
      schizophrenia 1 (DISC1) gene in the 129 mouse strain suggests that these mice may
      be exploited as a 'naturally occurring' model of schizophrenia. The aim of this
      present study was to assess cognition and behavioural flexibility of 129S2/SvHsd
      mice in comparison with C57BL/6J mice in the Barnes maze, using three different
      maze variations that consisted of either 8, 16 or 32 holes. Whereas C57BL/6J mice
      were able to perform both acquisition and reversal learning in all three mazes,
      129S2/SvHsd mice displayed impairments dependent on the complexity of the test.
      Intact acquisition and reversal occurred in the 8-hole maze; intact acquisition,
      but impaired reversal, was evident in the 16-hole maze and impaired acquisition
      was evident in the most difficult 32-hole test. Furthermore, analysis of search
      strategies confirmed strain differences in the adoption of spatial searches
      across both acquisition and reversal trials. 129S2/SvHsd mice displayed fewer
      spatial-type trials than C57BL/6J mice and instead employed more random or
      serial/chaining search behaviours. The deficits observed in both cognition and
      behavioural flexibility support the notion of the 129 mouse strain as a potential
      model of schizophrenia.

PMID- 30212385
TI  - Turkish adaptation of Parkinson fatigue scale and investigating its psychometric
      properties.
AB  - Parkinson's disease (PD) is one of the most common chronic degenerative diseases
      of the nervous system. In PD, nonmotor symptoms are seen as frequently as motor
      symptoms. Fatigue can occur in all stages of PD and leads to significant
      disabilities. The aim of this study was to investigate the psychometric
      properties of the Turkish version of Parkinson fatigue scale (PFS). Ninety-six
      patients with idiopathic PD were included in this study with a cross-sectional
      and test-retest design. Structural validity, internal consistency and test-retest
      reliability of PFS were analyzed. For convergent validity, fatigue severity scale
      and modified fatigue impact scale were used. Internal consistency was determined
      by the Cronbach's alpha coefficient. For test-retest reliability, PFS was
      repeated after a 7-14-day period. Significant strong correlations were found
      between the PFS and the fatigue severity scale (rs=0.844) and the modified
      fatigue impact scale (rs=0.764), which indicate a high convergent validity. The
      Cronbach's alpha coefficient, which indicates the internal consistency of the
      scale, was calculated as 0.947. The test-retest reliability was found to be high
      (intraclass correlation coefficient=0.928). This study suggests that the Turkish
      version of PFS is valid and reliable. PFS is suitable for use by researchers and
      healthcare professionals to assess fatigue in Turkish-speaking patients with PD.

PMID- 30212386
TI  - Overachieving Municipalities in Public Health: A Machine-learning Approach.
AB  - BACKGROUND: Identifying successful public health ideas and practices is a
      difficult challenge towing to the presence of complex baseline characteristics
      that can affect health outcomes. We propose the use of machine learning
      algorithms to predict life expectancy at birth, and then compare health-related
      characteristics of the under- and overachievers (i.e., municipalities that have a
      worse and better outcome than predicted, respectively). METHODS: Our outcome was
      life expectancy at birth for Brazilian municipalities, and we used as predictors
      60 local characteristics that are not directly controlled by public health
      officials (e.g., socioeconomic factors). RESULTS: The highest predictive
      performance was achieved by an ensemble of machine learning algorithms (cross
      validated mean squared error of 0.168), including a 35% gain in comparison with
      standard decision trees. Overachievers presented better results regarding primary
      health care, such as higher coverage of the massive multidisciplinary program
      Family Health Strategy. On the other hand, underachievers performed more cesarean
      deliveries and mammographies and had more life-support health equipment.
      CONCLUSIONS: The findings suggest that analyzing the predicted value of a health
      outcome may bring insights about good public health practices.

PMID- 30212387
TI  - 17th Biennial Meeting of the International Gynecologic Cancer Society Kyoto,
      Japan September 14-16, 2018.

PMID- 30212388
TI  - Evaluation of Urine Choline Levels in Women With and Without Overactive Bladder
      Syndrome.
AB  - OBJECTIVE: The objective of this study was to determine whether levels of choline
      (Ch) differ in women with and without overactive bladder (OAB) symptoms. METHODS:
      New patients were evaluated using the overactive bladder symptom score; Medical,
      Epidemiologic, and Social Aspects of Aging (MESA) urgency incontinence
      questionnaire; and Impact Questionnaire 7 and provided a urine sample. Patients
      were stratified into asymptomatic controls, scoring 0 on overactive bladder
      symptom score and the MESA questionnaire, and patients with OAB and urgency
      incontinence (OAB-wet). Patients with conditions predisposing to OAB or had a
      history of OAB treatment were excluded. Choline detection was accomplished using
      a commercially available kit. Wilcoxon rank sum test and Fisher exact test were
      used to express differences between groups. Spearman rho correlation was used to
      determine the relationship between Ch and questionnaire scores. Logistic
      regression was used to identify significant variables associated with OAB.
      RESULTS: Sixty-three women were included in the final analysis. Patients with OAB
      wet were older (P = 0.001), more likely to be obese (P = 0.04), had greater
      apical descent (P = 0.02), were more likely to be postmenopausal (P = 0.01), and
      were more likely to have stress incontinence (P = 0.005). Choline was 34.8% lower
      in OAB compared with the controls (P = 0.014). Lower Ch levels were associated
      with higher MESA (Spearman rho = -0.311, P = 0.03). After logistic regression,
      lower Ch (adjusted odds ratio [aOR], 0.97; 95% confidence interval [CI], 0.96
      0.98), age (aOR, 1.12; 95% CI, 1.08-1.18), and body mass index (aOR, 1.09; 95%
      CI, 1.01-1.18) were significantly associated with OAB-wet. CONCLUSIONS: Choline
      levels are significantly decreased in women complaining of OAB with urgency
      incontinence, and lower levels are associated with higher MESA scores.

PMID- 30212389
TI  - Golden Hour Protocol for Preterm Infants: A Quality Improvement Project.
AB  - BACKGROUND: Preterm infants are a vulnerable patient population, especially
      during the first hours of life. Hypothermia, hypoglycemia, and early-onset sepsis
      are common problems related to prematurity. Implementation of a Golden Hour
      protocol has been shown to improve outcomes for preterm infants. PURPOSE: To
      evaluate the effectiveness of a Golden Hour protocol for infants born at less
      than 32 weeks' gestation on improving the admission process in a military care
      facility. Specific aims focused on temperature, time to initiation of intravenous
      (IV) fluids, time to administration of antibiotics, and time to close of the
      incubator top. METHODS: A pre-/postdesign was used to compare outcomes from
      preimplementation to postimplementation. Predata were collected using electronic
      health record chart review and postdata were collected from the Neonatal
      Intensive Care Unit admission worksheet. RESULTS: Although we did not find
      statistical significance, we found that more infants had a temperature greater
      than 36.5 degrees C within 1 hour of birth and decrease in time to initiation of
      IV fluids and antibiotics from preimplementation to postimplementation, which is
      clinically significant. Time to close of the incubator top remained greater than
      1 hour. IMPLICATIONS FOR PRACTICE: Implementation of a Golden Hour protocol
      provides a guide to caring for preterm infants during the first hour of life to
      improve patient outcomes. Involvement of key stakeholders and staff education are
      key to successful implementation. IMPLICATIONS FOR RESEARCH: Researchers should
      examine long-term outcomes related to implementation of a Golden Hour protocol in
      future studies. Future quality improvement projects should include the
      effectiveness of similar protocols and address possible barriers.

PMID- 30212390
TI  - Recurrent Mutations in APC and CTNNB1 and Activated Wnt/beta-catenin Signaling in
      Intraductal Papillary Neoplasms of the Bile Duct: A Whole Exome Sequencing Study.
AB  - This study aimed to elucidate the genetic landscape of biliary papillary
      neoplasms. Of 28 cases examined, 7 underwent whole exome sequencing, while the
      remaining 21 were used for validation studies with targeted sequencing. In the
      whole exome sequencing study, 4/7 cases had mutations in either APC or CTNNB1,
      both of which belong to the Wnt/beta-catenin pathway. Somatic mutations were also
      identified in genes involved in RAS signaling (KRAS, BRAF), a cell cycle
      regulator (CDC27), histone methyltransferase (KMT2C, KMT2D), and DNA mismatch
      repair (MSH3, MSH6, PMS1). Combined with discovery and validation cohorts,
      mutations in APC or CTNNB1 were observed in 6/28 subjects (21%) and were mutually
      exclusive. When the cases were classified into intraductal papillary neoplasms of
      the bile duct (IPNBs, n=14) and papillary cholangiocarcinomas (n=14) based on the
      recently proposed classification criteria, mutations in APC and CTNNB1 appeared
      to be entirely restricted to IPNBs with 6/14 cases (43%) harboring mutations in
      either gene. These genetic alterations were detected across the 3 nonintestinal
      histologic types. In immunohistochemistry, the aberrant cytoplasmic and/or
      nuclear expression of beta-catenin was found in not only 5/6 IPNBs with APC or
      CTNNB1 mutations, but also 6/8 cases with wild-type APC and CTNNB1 (total 79%).
      In addition, APC and CTNNB1 alterations were exceptional in nonpapillary
      cholangiocarcinomas (n=29) with a single case harboring CTNNB1 mutation (3%).
      This study demonstrated recurrent mutations in APC and CTNNB1 in nonintestinal
      type IPNBs, suggesting that activation of the Wnt/beta-catenin signaling pathway
      is relevant to the development and progression of IPNBs.

PMID- 30212391
TI  - FIGO Versus Silverberg Grading Systems in Ovarian Endometrioid Carcinoma: A
      Comparative Prognostic Analysis.
AB  - The International Federation of Obstetrics and Gynecology (FIGO) grading system
      for endometrial carcinoma is currently applied to ovarian endometrioid carcinoma
      (OEC) in many practices. However, previous reports claim superior prognostication
      by using the Silverberg grading system for ovarian carcinoma. Thus, a thorough
      comparison between FIGO and Silverberg in OEC is still warranted. A total of 72
      OECs diagnosed at our institution were independently graded using both systems.
      Grade (G) following Silverberg was based on combined scores for architecture,
      nuclear atypia, and mitotic activity. FIGO grading was based on the % of
      nonsquamous solid component; severe atypia warranted upgrade to the architectural
      FIGO grade (G1 to G2 or G2 to G3). Case grouping by grade was correlated with
      disease-free (DFS), disease-specific (DSS), and overall (OS) survival. Eleven
      (15.3%) OECs were bilateral, 26 (36.1%) had ovarian surface involvement, and 12
      (16.7%) had lymphovascular space invasion. Forty-seven OECs were stage I (65%),
      16 (22%) stage II, and 9 (13%) stage III. Median follow-up period was 62 months
      (range: 1 to 179 mo). Median DFS was 60.5 months (1 to 179 mo); median OS was 61
      months (1 to 179 mo). Sixteen (22%) OECs recurred and 9 (13%) patiets died of
      disease. In univariate analysis, both FIGO and Silverberg correlated
      significantly with DFS, DSS, and OS (all with P<0.05). However, when compared in
      multivariate analysis, only Silverberg retained statistical correlation with
      survival (P<0.05). G1+G2 OEC by Silverberg had significantly better DFS, DSS, and
      OS compared with G3; such separation was not seen with FIGO. Survival was similar
      in Silverberg G1 and G2 tumors even 5 years after diagnosis, whereas FIGO G2
      tumors had survival approaching G1 in the first 5 years, but declined after the 5
      year mark approaching G3 tumors. Tumor laterality, lymphovascular space invasion,
      and stage also correlated with outcome. Stage showed prognostication superior to
      all other variables in multivariate analysis. As currently defined, the
      Silverberg grading system is a better predictor of survival than FIGO. Such
      differences may be explained by the G2 OEC groups, with G2 Silverberg clustering
      with G1 tumors, and having a more favorable behavior compared with G2 FIGO. Thus,
      Silverberg may be preferable in order to stratify patients in low and high-risk
      categories for prognosis and disease management.

PMID- 30212392
TI  - SATB2 Is Superior to CDX2 in Distinguishing Signet Ring Cell Carcinoma of the
      Upper Gastrointestinal Tract and Lower Gastrointestinal Tract.
AB  - Signet ring cell carcinomas of the gastrointestinal (GI) tract are clinically
      aggressive neoplasms with frequent intra-abdominal metastases at initial
      presentation. Currently available immunohistochemistry (IHC) markers cannot
      distinguish signet ring cell carcinomas of the lower GI tract and upper GI tract,
      suggesting the need for more specific diagnostic markers. SATB2 is a novel,
      sensitive marker for colorectal carcinoma. We hypothesized that SATB2 IHC can
      reliably identify primary and metastatic signet ring cell carcinomas of lower GI
      tract origin. SATB2 and CDX2 IHC was performed on 159 primary (n=93) and
      metastatic (n=66) signet ring cell carcinomas of GI tract origin and 13
      metastatic breast carcinomas with signet ring cell features. Positive SATB2
      expression (SATB2) was identified in 82% (27/33) of appendiceal, 88% (43/49) of
      colorectal, 13% (7/54) of gastric, and 35% (8/23) of esophageal/esophagogastric
      junction signet ring cell carcinomas. Primary and metastatic signet ring cell
      carcinomas of lower GI tract origin were more frequently SATB2 than those from
      upper GI tract (70/82, 85% vs. 15/77, 19%, P<0.01). Compared with CDX2, SATB2 and
      dual-positive staining for SATB2 and CDX2 both had higher specificities for
      signet ring cell carcinomas from the lower GI tract (81% vs. 49% and 86% vs. 49%,
      respectively, P<0.01 for both). Two (15%) metastatic breast carcinoma were SATB2,
      but all 13 demonstrated negative CDX2 staining. In summary, our results show
      SATB2 is a relatively specific immunohistochemistry marker for both metastatic
      and primary signet ring cell carcinomas of lower GI tract origin.

PMID- 30212393
TI  - Cancerization of the Pancreatic Ducts: Demonstration of a Common and Under
      recognized Process Using Immunolabeling of Paired Duct Lesions and Invasive
      Pancreatic Ductal Adenocarcinoma for p53 and Smad4 Expression.
AB  - Invasive pancreatic ductal adenocarcinoma (PDAC) can infiltrate back into and
      spread along preexisting pancreatic ducts and ductules in a process known as
      cancerization of ducts (COD). Histologically COD can mimic high-grade pancreatic
      intraepithelial neoplasia (HG-PanIN). We reviewed pancreatic resections from 100
      patients with PDAC for the presence or absence of ducts with histologic features
      of COD. Features supporting COD included adjacent histologically similar invasive
      PDAC and an abrupt transition between markedly atypical intraductal epithelium
      and normal duct epithelium or circumferential involvement of a duct. As the TP53
      and SMAD4 genes are frequently targeted in invasive PDAC but not HG-PanIN, paired
      PDAC and histologically suspected COD lesions were immunolabeled with antibodies
      to the p53 and Smad4 proteins. Suspected COD was identified on hematoxylin and
      eosin sections in 89 (89%) of the cases. Immunolabeling for p53 and Smad4 was
      performed in 68 (76%) of 89 cases. p53 was interpretable in 55 cases and all 55
      (100%) cases showed concordant labeling between COD and invasive PDAC. There was
      matched aberrant p53 immunolabeling in 37 (67%) cases including overexpression in
      30 (55%) cases and lack of expression in 7 (13%) cases. Smad4 immunolabeling was
      interpretable in 61 cases and 59 (97%) cases showed concordant labeling between
      COD and invasive PDAC. Matched loss of Smad4 was seen in 28 (46%) cases. The
      immunolabeling of invasive PDAC and COD for p53 and Smad4 supports the high
      prevalence of COD observed on hematoxylin and eosin and highlights the utility of
      p53 and Smad4 immunolabeling in differentiating COD and HG-PanIN.

PMID- 30212395
TI  - The Effect of Hormonal Contraception on Pharmacokinetics of Vaginal Tenofovir in
      Healthy Women: Increased Tenofovir Diphosphate in Injectable Depot
      Medroxyprogesterone Acetate users.
AB  - OBJECTIVE: Endogenous and exogenous contraceptive hormones may affect mucosal
      pharmacokinetics of topical anti-retrovirals such as tenofovir. We present
      pharmacokinetic data from healthy women using tenofovir vaginal gel, at baseline
      (follicular and luteal phases) and after oral contraceptive pill (OCP) or depot
      medroxyprogesterone acetate (DMPA) use. METHODS: CONRAD A10-114 was a
      prospective, interventional, open-label, parallel study. We enrolled 74 women and
      60 completed the study (32 and 28 who selected OCPs or DMPA, respectively).
      Participants used 2 doses of tenofovir gel separated by 2 hours, without
      intercourse, and were examined 3 or 11 hours after the last dose. We assessed
      pharmocokinetics in plasma, cervico-vaginal (CV) aspirate and vaginal tissue.
      RESULTS: In general, there were no significant differences in mucosal tenofovir
      and tenofovir-diphosphate concentrations (p>0.23) in the follicular and luteal
      phases, except for lower mean tenofovir tissue concentrations (p<0.01) in the
      follicular phase. Tenofovir concentrations significantly decreased in CV aspirate
      (p<0.01) after contraceptive use, but overall remained very high (>10 ng/mL).
      Mean tissue tenofovir-diphosphate increased to 6,229 fmol/mg after DMPA use
      compared to 3,693 and 1,460 fmol/mg in the follicular and luteal phases
      respectively (p<0.01). The molecular conversion of tenofovir into tenofovir
      diphosphate was more effective in DMPA users (molecular ratio of 2.02 vs 0.65
      luteal phase, p<0.01). CONCLUSIONS: Both menstrual cycle phase and exogenous
      hormones affect topical tenofovir mucosal and systemic pharmacokinetics. However,
      high levels of tenofovir and tenofovir-diphosphate were observed in the CV mucosa
      in the presence or absence of OCPs and DMPA, with tissue levels exceeding
      benchmarks of predicted mucosal anti-HIV efficacy (tenofovir > 1,00 ng/mL in CV
      aspirate and tenofovir-diphosphate > 1,000 fmol/mg).

PMID- 30212394
TI  - Effect of Antiretroviral Therapy on Treatment Outcomes in a Prospective Study of
      Extensively Drug-Resistant Tuberculosis (XDR-TB) HIV Coinfection Treatment in
      KwaZulu-Natal, South Africa.
AB  - BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB)/HIV coinfection has
      been associated with high mortality and poor TB outcomes. We performed a
      prospective study to comprehensively characterize a cohort of patients with XDR
      TB. METHODS: Adult patients with XDR-TB were enrolled at treatment initiation at
      a TB referral hospital in KwaZulu-Natal Province, South Africa, and followed
      through the end of treatment. Clinical data, questionnaires, adherence data, and
      sputum were collected monthly. Whole genome sequencing was performed on baseline
      Mycobacterium tuberculosis (MTB) isolates. Treatment outcomes were defined using
      standard definitions. RESULTS: One hundred five patients with XDR-TB (76.1% HIV
      infected) were enrolled from August 2009 to July 2011. Among HIV-coinfected
      patients, 82.5% were on antiretroviral therapy initially and 93.8% cumulatively
      over the study period. At 24 months, 31.4% had a successful outcome and 68.6% had
      an unsuccessful outcome with 41% mortality. Antiretroviral therapy was associated
      with improved mortality in HIV-coinfected patients (P = 0.05), as was TB culture
      conversion (P < 0.0001). On whole genome sequencing, most strains were LAM4/KZN
      lineage (68%), with few single nucleotide polymorphism differences. CONCLUSIONS:
      Despite improved HIV care, treatment outcomes and mortality were only modestly
      improved compared with previous South African XDR-TB/HIV treatment cohorts. Of
      note, this study was completed before the introduction of new antimycobacterial
      agents (eg, bedaquiline and delamanid). As new TB drugs and regimens become
      available, it is important to monitor treatment to ensure that benefits seen in
      clinical trials are reproduced in high-burden, low-resource settings.

PMID- 30212396
TI  - Why Do You Keep Telling Me That Drug-Drug Interactions Are Important in
      Psychopharmacology When I Do Not See Them in My Clinical Practice?: My Failure to
      Convince Clinicians.

PMID- 30212397
TI  - A Compatibility Guide for the Orthopaedic Surgeon Planning to Perform Hardware
      Removal Surgery.
AB  - BACKGROUND: Removal of previously placed orthopaedic implants is a commonly
      performed procedure worldwide. Given the diversity of orthopaedic implant
      manufacturers, surgeons may be uncertain whether they have the appropriate
      screwdriver on site. The purpose of this study was to assess the compatibility of
      screw head and size configurations from various orthopaedic manufacturers with
      two commonly used universal screw removal sets. METHODS: Inclusion of orthopaedic
      implant manufacturers was determined by market share based on industry-monitoring
      financial firms. Screw size and drive type for the top grossing orthopaedic
      implant manufacturers were collected and recorded. Screw and screwdriver
      compatibility was assessed and compared with two commonly used universal screw
      removal sets. RESULTS: In total, six orthopaedic implant companies with commonly
      implanted screws throughout the appendicular skeleton were included. The data
      were compiled in table format with noncannulated, cannulated, and locking screw
      offerings separated by the screw size and manufacturer. Guidewire size
      compatibility for cannulated offerings was also assessed. CONCLUSIONS: Given the
      ubiquity of implanted orthopaedic implant, removal must be as safe, planned, and
      controlled as possible. The data in this article provide an inclusive,
      centralized resource for surgeons looking to confirm the compatibility of
      previously implanted screws and available removal equipment at their institution.

PMID- 30212398
TI  - Role of Relative Malnutrition in Exercise-Hypogonadal Male Condition.
AB  - OBJECTIVE: Exercise Hypogonadal Male Condition (EHMC) is a well-recognized
      condition in women but much less understood in men. The aim of this case report
      is to highlight exercise induced hypogonadotropic hypogonadism in a male who
      recovered with lifestyle modifications. METHODS: We report a case of an
      adolescent male who developed hypogonadotropic hypogonadism secondary to
      excessive exercise and malnutrition that was followed up for a year without
      exogenous testosterone supplementation. Informed consent was obtained from the
      patient for his information to be used in a manuscript submitted to a journal.
      RESULTS: 18-year-old adolescent male presented to the clinic with symptoms of
      fatigue and low endurance, low libido and lack of morning erections. At the time
      of his presentation, he was running about 60 miles per week for school cross
      country team in addition to cross training with kick-boxing. Physical examination
      was remarkable for low BMI (Body mass index) of 19 but was otherwise normal.
      Biochemical work up confirmed hypogonadotropic hypogonadism and a mild
      pancytopenia. Other pituitary laboratory values and MRI of the brain were
      unremarkable. Bone marrow biopsy performed for anemia showed features consistent
      with malnutrition. With a working diagnosis of EHMC, he was advised to reduce the
      frequency and intensity of his exercise and increase calorie intake. Cell counts
      and testosterone levels normalized and his symptoms resolved without any further
      interventions. CONCLUSION: Significant reversible hypogonadism can develop after
      intensive and prolonged exercise. One of the mechanisms of hypogonadism in
      endurance athletes performing intensive exercise could be relative malnutrition.
      Further studies to evaluate the role of nutrition and BMI in male endurance
      athletes presenting with hypogonadism are needed to identify the underlying
      mechanism of this condition.

PMID- 30212399
TI  - Concussion History, Reporting Behaviors, Attitudes, and Knowledge in Jockeys.
AB  - OBJECTIVE: To examine concussion history, knowledge, and attitudes among Irish
      professional and amateur jockeys. DESIGN: Cross-sectional survey. SETTING:
      Questionnaire was distributed through e-mails sent to all licensed jockeys, over
      social media and during professional and amateur race meetings. PARTICIPANTS: An
      average of 23.6% (12%-44%) Irish professional and amateur jockeys (n = 119)
      holding a license in 2017. MAIN OUTCOME MEASURES: Jockeys reported their previous
      concussion history, actions after their most recent concussion and responded to
      questions examining their knowledge and attitudes toward concussion. RESULTS:
      Amateur (32.4%) and professional (19.6%) jockeys, who were never medically
      diagnosed over their career, suspected that they had sustained a concussion.
      Jockeys displayed good knowledge of concussion signs and symptoms; yet, one in 2
      jockeys would continue to ride out the same day if they suspected they had a
      concussion. They were less likely if they had a race that day. Reasons for
      continuing to ride include not considering a concussion as serious (85.7%); risk
      of losing the ride (84.0%); not wanting to let anyone down (77.8%); and
      considered it a sign of weakness (74.1%). Risky behavior was more common after a
      suspected concussion than a medically diagnosed concussion. CONCLUSIONS:
      Underreporting of concussions is proposed as a serious concern, and concussion
      understanding and attitudes can impact reporting. To address the issue of
      underreporting of concussions in Irish horseracing, there is a need to educate
      jockeys and the wider racing community on the importance of timely concussion
      assessments and access to appropriate management systems.

PMID- 30212400
TI  - Meta-analysis of meta-analyses in oncologic positron emission tomography.
AB  - OBJECTIVES: As PET has become a standard of treatment in patients with cancer,
      publications of oncologic PET have grown sharply. We aimed to organize the data
      of meta-analyses of oncologic PET and assess the quality of studies. MATERIALS
      AND METHODS: The inclusion criteria were studies that meta-analyzed to combine
      the data from multiple studies of oncologic PET. We used the Preferred Reporting
      Items for Systematic Reviews and Meta-analyses (PRISMA) to assess the reporting
      quality of the included studies. RESULTS: A total of 254 meta-analyses were
      eligible for inclusion in the study. The peak number of publications increased up
      to 42 in 2014. Lung (n=39, 15.4%) is the most common site of tumor included in
      meta-analysis with oncologic PET. Overall, 84% of studies were categorized into
      diagnostic test accuracy reviews (n=214). Studies published in 2010 or later
      (n=213) showed higher PRISMA scores than those published in 2009 or before.
      CONCLUSION: A large number of meta-analyses are published in the field of
      oncologic PET. Meta-analyses in oncologic PET seem to be cited more often than
      regular research papers. The overall quality of studies is low; however, they
      showed improvement after PRISMA statement.

PMID- 30212401
TI  - Docking, synthesis, in-vitro evaluation, and optimization of reaction conditions
      for direct radiolabeling of CGPRPPC with technetium-99m through the GAGG
      sequence.
AB  - OBJECTIVE: With respect to the reported promising results of cyclic peptide
      CGPRPPC in early detection of thrombotic lesions, we developed a practical
      approach for technetium-99m labeling of this peptide using the Glycine-Alanine
      Glycine-Glycine (GAGG) sequence as a chelating moiety. MATERIALS AND METHODS: The
      peptide conjugated to GAGG was prepared using the solid-phase method. The
      optimization of radiolabeling conditions was performed on the basis of such
      variables as incubation time, reaction temperature, pH, and concentration of
      peptide and stannous chloride. Moreover, the stability and fibrin-binding
      affinity of the radiolabeled peptide were measured. The peptide-fibrin
      interactions were analyzed by docking studies using HEX and Auto dock 4.2.
      Softwares. RESULTS: The amounts of synthesized peptide and stannous chloride
      required for optimal radiolabeling through GAGG were 10 umol/l and 5 ug,
      respectively. The best radiochemical purity% (>93%) was achieved at pH 7-8 within
      15 min and a reaction temperature of 37 degrees C. On the basis of in silico and
      in-vitro results, the GAGG-conjugated CGPRPPC peptide showed better binding
      affinity versus the HYNIC-conjugated one. CONCLUSION: We could radiolabel the
      fibrin-targeting peptide with high radiochemical purity% and stability during a
      short incubation period without a boiling step. Compared with the HYNIC
      conjugated peptide, a higher binding affinity was found. Therefore, the GAGG
      chelating moiety possesses a considerable potentiality in Technetium 99m labeling
      of peptides while CGPRPPC maintains its binding properties to thrombotic lesions.

PMID- 30212402
TI  - Fecal calprotectin is significantly linked to azathioprine metabolite
      concentrations in Crohn's disease.
AB  - BACKGROUND: The value of therapeutic drug monitoring during azathioprine (AZA)
      therapy with respect to clinical outcomes has been convincingly demonstrated in
      recent meta-analyses. However, the association between AZA metabolites and the
      mucosal state in inflammatory bowel disease is largely unclear. AIMS: We
      investigated the association between AZA's active metabolite 6-thioguanine
      nucleotides (6-TGN) and fecal calprotectin (FC) as a well-validated surrogate
      marker of mucosal inflammation in patients with Crohn's disease (CD) on AZA
      monotherapy. PATIENTS AND METHODS: Of 443 6-TGN measurements, 140 values from 88
      patients with CD on AZA monotherapy visiting the inflammatory bowel disease
      outpatient clinic between 2009 and 2016 were retrospectively analyzed. In a
      subcohort with serial 6-TGN measurements, longitudinal FC measurements in
      patients with versus without intervention (dose increase, allopurinol, and
      education) were assessed. RESULTS: In patients with 6-TGN concentrations within a
      predefined range (250-450 pmol/8*10 red blood cells), FC was significantly lower
      (median: 119.5 vs. 327.2 mg/kg, P=0.003), and hemoglobin as well as serum protein
      concentrations were significantly higher than in patients with 6-TGN outside of
      this range. C-reactive protein and transferrin saturation were not different. In
      the longitudinal cohort, 6-TGN increased in the intervention group, but only a
      minority reached the defined range; no significant change in FC was observed.
      CONCLUSION: This study is the first to show that in patients with CD receiving
      AZA monotherapy, 6-TGN concentrations within a defined range (250-450 pmol/8*10
      red blood cells) are associated with significantly lower FC. A treat-to-target
      concept directed by 6-TGN to reach mucosal healing may thus be a promising
      approach (DRKS00013246).

PMID- 30212403
TI  - Daily or on-demand oral tenofovir disoproxil fumarate/emtricitabine for HIV pre
      exposure prophylaxis: experience from a hospital-based clinic in France.
AB  - BACKGROUND: On-demand oral tenofovir disoproxil fumarate and emtricitabine
      (TDF/FTC) has been approved for pre-exposure prophylaxis (PrEP) in MSM in France
      following the results of clinical studies, but data are limited on real-world
      experience. DESIGN: A single-center, open-label, prospective cohort study that
      recruited people at high risk of HIV infection in Paris. METHODS: Participants
      were enrolled in a single hospital-based outpatient clinic and were proposed to
      start PrEP with daily or on demand TDF/FTC. At baseline and every 3 months
      thereafter, patients were tested for HIV and creatinine plasma levels, and data
      on sexual behavior, other sexually transmitted infections (STIs), and
      tolerability were collected. RESULTS: From 10 November 2015 to 30 April 2017,
      1069 patients were screened and 1049 (98.1%) started PrEP. Median age was 36
      years, 99.4% were MSM with a median number of partners of 10, and 793 (75.6%)
      opted for on demand PrEP. Over 486 person-years of follow-up, four HIV-infections
      were diagnosed in poorly or nonadherent patients (incidence 0.82/100 person
      years). Rate of condomless sex at last intercourse increased from 53.3% at
      baseline to 79% at month 12 (P < 10), but increase in bacterial STI rates was
      modest (14.6% at baseline vs. 19.2% at month 12; P < 10). Most adverse events
      were gastrointestinal and did not lead to PrEP discontinuation. CONCLUSIONS: Most
      PrEP users were high-risk MSM and opted for on-demand PrEP. PrEP use was
      associated with a low HIV incidence and a high rate of condomless sex with a
      modest increase in bacterial STIs.

PMID- 30212404
TI  - Similar tenofovir hair concentrations in men and women after directly observed
      dosing of tenofovir disoproxil fumarate/emtricitabine: implications for
      preexposure prophylaxis adherence monitoring.
AB  - OBJECTIVES: Women likely require higher adherence than men to preexposure
      prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)
      for similar efficacy. Pharmacologic metrics of adherence predict efficacy better
      than self-report, but expected drug levels (adherence benchmarks) must be
      established using directly observed therapy. We sought to evaluate whether
      tenofovir hair concentrations differ between women and men receiving directly
      observed TDF/FTC. METHODS: We assessed tenofovir hair concentrations in HIV
      uninfected volunteers randomized to receive 100%, 67%, or 33% of daily dosing of
      TDF/FTC for 12 weeks (DOT-DBS, NCT02022657). Hair samples were collected at
      dosing weeks 4, 8, and 12 and every 3 weeks during a 12-week washout. Tenofovir
      concentrations in the proximal 1.5 cm of hair (representing ~6 weeks of exposure)
      were analyzed using liquid chromatography/tandem mass spectrometry. Linear
      regression was used to model tenofovir hair concentrations in terms of sex, doses
      over the prior 6 weeks, and number of days since last dose. RESULTS: A total of
      264 hair samples were analyzed from 23 female and 24 male participants. Female
      participants had similar tenofovir hair concentrations to men (estimated fold
      difference 0.92, 95% CI 0.75-1.13, P = 0.43). The estimated fold-difference in
      tenofovir levels for female versus male participants did not appreciably change
      when age (0.93, 95% CI 0.76-1.15), weight (0.89, 95% CI 0.71-1.11), or
      race/ethnicity (0.95, 95% CI 0.77-1.17) were added to the model. CONCLUSION:
      Women and men have similar adherence benchmarks for tenofovir in hair samples. As
      pharmacokinetic metrics are increasingly used for PrEP monitoring, these findings
      provide guidance for assessing adherence via hair concentrations.

PMID- 30212405
TI  - HIV DNA decay during antiretroviral therapy: lessons from a clinic-based cohort
      study.

PMID- 30212406
TI  - Measurement of soluble glycoprotein VI in studies of abacavir-based therapy:
      concerns about test precision.

PMID- 30212408
TI  - High rates of incident diabetes and prediabetes are evident in men with treated
      HIV followed for 11 years: Erratum.

PMID- 30212409
TI  - The pharmacology of executive functioning.

PMID- 30212407
TI  - 'Discovering' primary effusion lymphoma in Malawi.

PMID- 30212410
TI  - Anterior-Segment Optical Coherence Tomography and Scanning Electron Microscopy to
      Evaluate Corneal Epithelial Changes in Patients Undergoing Glaucoma Therapy.
AB  - PURPOSE: To measure corneal epithelial thickness (CET) in patients with glaucoma
      using anterior-segment optical coherence tomography and to evaluate CET changes
      in relation to corneal epithelial microvilli analyzed by scanning electron
      microscopy (SEM). METHODS: Twenty-two eyes (16 patients) being treated with
      preservative-containing topical medications and 12 normal eyes underwent anterior
      segment optical coherence tomography imaging using RTVue-100. The CET maps
      generated corresponded to a 6-mm diameter area of cornea that was divided into 17
      sectors. We compared the CETs of each sector obtained in the glaucomatous group
      with those obtained in the control group. RESULTS: Glaucomatous eyes were divided
      into 2 groups based on the number of microvilli on SEM: group 1 (6 eyes) = grades
      1 and 2 at SEM (range: 500-3000) and group 2 (10 eyes) = grades 3 and 4 at SEM
      (range: 0-500). Four CET sectors were significantly thinner in group 1 than in
      normal eyes: central (P = 0.012), superior (P = 0.005), temporal paracentral (P =
      0.003), and temporal midperipheral (P = 0.023). No significant differences were
      observed between group 2 and normal eyes. CET sectors were significantly thinner
      in group 1 than in group 2 only in the superior (P = 0.024) and superior-temporal
      paracentral (P = 0.020) sectors. CET progressively increased in patients with
      glaucoma as the number of corneal epithelial microvilli decreased. CONCLUSIONS:
      CET and corneal epithelial microvilli are new parameters with which to evaluate
      early stages of corneal epithelial changes during glaucoma therapy. In advanced
      stages of corneal epithelial damage, SEM evaluation reveals ultrastructural
      epithelial changes that may not be observed on CET measurements.

PMID- 30212411
TI  - Penetrating Keratoplasty Using the Femtosecond Laser: A Comparison of
      Postoperative Visual Acuity and Astigmatism by Suture Pattern.
AB  - PURPOSE: To compare the effect of 3 common suturing techniques on eyes that
      received femtosecond laser-enabled penetrating keratoplasty (FLEK) with a zig-zag
      configuration at the Gavin Herbert Eye Institute, University of California-
      Irvine, California. METHODS: This is a retrospective chart review of a series of
      319 eyes of 286 patients who underwent FLEK with a zig-zag configuration. One
      hundred fifty-seven eyes had running sutures, 136 eyes had simple interrupted
      sutures, and 26 eyes had combined sutures (single running and simple
      interrupted). The main outcome measures were uncorrected distance visual acuity,
      best spectacle-corrected visual acuity (BSCVA), and topographic astigmatism
      (TCyl). These parameters were recorded for the first year of follow-up regardless
      of suture removal status and also after full suture removal. RESULTS: At 3
      months, the BSCVA of the running, interrupted, and combined suture groups was
      0.22 (+/-0.2), 0.41 (+/-0.3), and 0.29 (+/-0.1), respectively (P < 0.01). The
      mean TCyl of the running, interrupted, and combined groups at 3 months was 3.95
      (+/-2.7), 6.41 (+/-4.4), and 5.44 (+/-3.3) D, respectively (P < 0.01) All sutures
      were removed in 190 of 319 eyes, and at the last recorded visit, the mean BSCVA
      was 0.18 (+/-0.2), 0.34 (+/-0.2), and 0.19 (+/-0.2) logarithm of the minimum
      angle of resolution in the running, interrupted, and combined groups,
      respectively (P < 0.01) and mean TCyl was 4.51 (+/-2.8), 5.62 (+/-3.7), and 4.57
      (+/-2.9) D, respectively (P = 0.11). CONCLUSIONS: Better visual acuity after full
      suture removal was observed in the running suture group; however, the subgroups
      of patients with keratoconus were similar after all sutures were removed.

PMID- 30212412
TI  - Morbidity and Mortality of Crystalloids Compared to Colloids in Critically Ill
      Surgical Patients: A Subgroup Analysis of a Randomized Trial.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
      BACKGROUND:: The multicenter randomized Colloids versus Crystalloids for the
      Resuscitation of the Critically Ill (CRISTAL) trial was designed to test whether
      colloids altered mortality compared to crystalloids in the resuscitation of
      intensive care unit patients with hypovolemic shock. This preplanned analysis
      tested the same hypothesis in the subgroup of surgical patients. METHODS: The
      CRISTAL trial prospectively defined patients as critically ill surgical patients
      whenever they underwent emergency or scheduled surgery immediately before or
      within 24 h of intensive care unit admission and had hypovolemic shock. The
      primary outcome measure was death by day 28. Secondary outcome measures included
      death by day 90, the need for renal replacement therapy, or the need for fresh
      frozen plasma transfusion. RESULTS: There were 741 critically ill surgical
      patients, 356 and 385 in the crystalloid and colloid arm, respectively. Median
      (interquartile range) age was 66 (52 to 76) yr, and 484 (65.3%) patients were
      male. Surgery was unscheduled in 543 (73.3%) cases. Mortality by day 28 did not
      significantly differ for crystalloids 84 (23.6%) versus colloids 100 (26%;
      adjusted odds ratio, 0.86; 95% CI, 0.61 to 1.21; P = 0.768). Death by day 90 (111
      [31.2%] vs. 122 [31.7%]; adjusted odds ratio, 0.97; 95% CI, 0.70 to 1.33; P =
      0.919) did not significantly differ between groups. Renal replacement therapy was
      required for 42 (11.8%) patients in the crystalloids arm versus 49 (12.7%) in the
      colloids arm (P = 0.871). CONCLUSIONS: The authors found no survival benefit when
      comparing crystalloids to colloids in critically ill surgical patients.

PMID- 30212413
TI  - Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short
      Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by
      L-Cysteine.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
      BACKGROUND:: Structure-activity studies were performed to identify a new
      neuromuscular blocking agent retaining the ultra-short acting characteristics of
      gantacurium, including degradation and reversal by L-cysteine, but lacking its
      histaminoid properties in man. CW 1759-50 has emerged from this program. METHODS:
      Adduction of CW 1759-50 with L-cysteine was studied by high-performance liquid
      chromatography and mass spectrometry. Institutional Animal Care and Use Committee
      approved comparisons of CW 1759-50 to gantacurium were performed in rhesus
      monkeys. ED95 for neuromuscular blockade was established. Spontaneous recovery
      was compared to reversal by L-cysteine in paired studies of boluses or infusions.
      In addition, changes in mean arterial pressure and heart rate after very large
      doses of 15 to 60 * ED95 were compared. RESULTS: The half-time of adduction of L
      cysteine to CW 1759-50 in vitro was 2.3 min. The ED95 of CW 1759-50 was 0.069 +/-
      0.02 mg/kg; ED95 of gantacurium was 0.081 +/- 0.05 mg/kg (P = 0.006). Duration of
      action (recovery to 95% twitch height after 98 to 99% blockade) was as follows:
      CW 1759-50, 8.2 +/- 1.5 min; and gantacurium, 7.4 +/- 1.9 min; (n = 8 and 9, P =
      0.355). Administration of L-cysteine (30 mg/kg) shortened recovery (i.e., induced
      reversal) from CW 1759-50 after boluses or infusions (P always less than 0.0001).
      Recovery intervals (5 to 95% twitch) ranged from 6.1 to 6.7 min (and did not
      differ significantly) after boluses of 0.10 to 0.50 mg/kg, as well as control
      infusions (P = 0.426 by analysis of variance). Dose ratios comparing changes of
      30% in mean arterial pressure or heart rate to ED95 for neuromuscular blockade
      (ED 30% Delta [mean arterial pressure or heart rate]/ED95) were higher for CW
      1759-50 than for gantacurium. CONCLUSIONS: CW 1759-50, similar to gantacurium, is
      an ultra-short acting neuromuscular blocking agent, antagonized by L-cysteine, in
      the monkey. The circulatory effects, however, are much reduced in comparison with
      gantacurium, suggesting a trial in humans.

PMID- 30212414
TI  - Management of Irreducible Hip Dislocations in Infants With Developmental
      Dysplasia of the Hip Diagnosed Below 6 Months of Age.
AB  - BACKGROUND: Infants with dislocated irreducible (D/I) hips can be substantially
      harder to treat than infants with dislocated but reducible hips. The purpose of
      this study was to compare treatment methods and outcomes for infants with D/I
      hips in order to optimize management of this difficult patient cohort. METHODS: A
      multicenter prospective hip dysplasia study database was analyzed from 2010 to
      2016. Infants aged below 6 months with clinically and radiologically confirmed
      D/I hips were included in the study. Teratological hips (syndromic/neuromuscular)
      were excluded. RESULTS: In total, 59 hips in 52 patients were included. All hips
      were clinically Ortolani negative and radiologically dislocated but irreducible
      on presentation and had at least 20 months of follow-up. Mean age at diagnosis
      was 1.9 months (range, 0.1 to 5.9 mo). There were 33 left hips, 12 right hips,
      and 14 bilateral hips (7 patients). In total, 48 of 59 hips were treated in
      Pavlik harness. The remainder were treated by alternative braces or primary
      closed or open reductions. Pavlik treatment was successful in 27 of 48 hips.
      Pavlik treatment was abandoned in 21 D/I hips, 3 due to femoral nerve palsy and
      the remainder due to failure to achieve reduction. There was no statistical
      correlation between Pavlik success and age at diagnosis (P=0.22), patient sex
      (P=0.61), or bilateral compared with unilateral D/I hips (P=0.07). Left hips were
      more likely to be successfully reduced in Pavlik harness than right hips
      (P=0.01). Five complications occurred: 3 patients developed femoral nerve palsy
      in Pavlik harness, while 2 patients developed avascular necrosis, both after
      failed Pavlik treatment and subsequent surgery. CONCLUSIONS: Pavlik harness
      treatment has been demonstrated to be a safe and sensible first-line treatment
      for infants with D/I hips. Left hips were more likely to be successfully reduced
      in Pavlik harness than right hips, but age, sex, and bilaterality were not
      correlated. The outcomes demonstrated from this multicentre prospective database
      inform management of this complex patient cohort. LEVEL OF EVIDENCE: Level II
      prognostic study: less-quality prospective study.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- 30212415
TI  - Copaiba Oil Attenuates Right Ventricular Remodeling by Decreasing Myocardial
      Apoptotic Signaling in Monocrotaline-Induced Rats.
AB  - There is an increase in oxidative stress and apoptosis signaling during the
      transition from hypertrophy to right ventricular (RV) failure caused by pulmonary
      arterial hypertension (PAH) induced by monocrotaline (MCT). In this study, it was
      evaluated the action of copaiba oil on the modulation of proteins involved in RV
      apoptosis signaling in rats with PAH. Male Wistar rats (+/-170 g, n = 7/group)
      were divided into 4 groups: control, MCT, copaiba oil, and MCT + copaiba oil. PAH
      was induced by MCT (60 mg/kg intraperitoneally) and, 7 days later, treatment with
      copaiba oil (400 mg/kg by gavage) was given for 14 days. Echocardiographic and
      hemodynamic measurements were performed, and the RV was collected for
      morphometric evaluations, oxidative stress, apoptosis, and cell survival
      signaling, and eNOS protein expression. Copaiba oil reduced RV hypertrophy (24%),
      improved RV systolic function, and reduced RV end-diastolic pressure, increased
      total sulfhydryl levels and eNOS protein expression, reduced lipid and protein
      oxidation, and the expression of proteins involved in apoptosis signaling in the
      RV of MCT + copaiba oil as compared to MCT group. In conclusion, copaiba oil
      reduced oxidative stress, and apoptosis signaling in RV of rats with PAH, which
      may be associated with an improvement in cardiac function caused by this
      compound.

PMID- 30212416
TI  - Evaluation of an Ion Trap Toxtyper Liquid Chromatography With An Ion Trap Mass
      Spectrometric Instrument (Toxtyper) for Drug of Abuse Screening in Oral Fluid.
AB  - BACKGROUND: Oral fluid (OF) is increasingly used as an alternative sample matrix
      in drug of abuse screening. Screening is commonly performed by immunoassays and
      results confirmed using laborious gas chromatography-mass spectrometry (GC-MS)
      based methods. Therefore, an easy to operate ion trap mass spectrometric (IT-MS)
      commercial screening method (Toxtyper; Bruker Daltronik, Bremen, Germany)
      combined with a laboratory-developed sample preparation procedure has been
      evaluated for their application to OF. METHODS: OF samples were subjected to
      protein precipitation followed by HybridSPE-Phospholipid extraction.
      Chromatographic separation was achieved by ultra-high-performance liquid
      chromatography; MS2/MS3 spectra were recorded by IT-MS and analyzed using a
      library provided by the manufacturer (Bruker Daltronik). The lower limit of
      detection, linearity, imprecision, inaccuracy, and specificity (interferences and
      matrix effects) were investigated for methadone, buprenorphine, pregabalin,
      fentanyl, amphetamine, 3,4-methylendioxy-N-methylamphetamine, cocaine,
      acetylcodeine, and nordiazepam, after spiking drug-free OF with these test
      substances. In addition, concordance between IT-MS results and gas chromatography
      tandem mass spectrometry, liquid chromatography-tandem mass spectrometry, or
      immunoassay (buprenorphine) results was investigated. RESULTS: No interferences
      or matrix effects were observed. The lower limit of detection for acetylcodeine,
      amphetamine, benzoylecgonine, methadone, and nordiazepam was below the common
      cutoffs for immunological screening assays and comparable to that of GC-MS.
      Imprecision and inaccuracy, both in- and between-series, were consistently <25%,
      except for buprenorphine. Toxtyper screening for pregabalin and fentanyl was less
      sensitive than a targeted liquid chromatography-tandem mass spectrometry assay. A
      very good concordance was found between the previous analytical approach and the
      new IT-MS method. CONCLUSIONS: The Toxtyper IT-MS is easy to use and can be
      applied for the screening of drug of abuse and the qualitative confirmation
      analysis in OF in a clinical toxicology service. Although intended for
      qualitative analysis, performance data suggest that the methods investigated may
      also be applicable for semiquantitative longitudinal follow-up.

PMID- 30212417
TI  - Childhood and Adolescent Cancer in the State of Pernambuco, Brazil: Incidence,
      Geographical Distribution, and Association With Environmental Health Indicators.

PMID- 30212418
TI  - Ethosuximide-induced Thrombocytopenia: A Case Report.

PMID- 30212419
TI  - Vitamin D Intake and Status of Children With Sickle Cell Disease in Montreal,
      Canada.
AB  - Sickle cell disease (SCD) and vitamin D deficiency share manifestations such as
      bone complications and bony pains. Canadian SCD children are characterized by
      compromised sun exposure all year long and potential dietary deficiency, which
      combined to SCD-causing high nutritional demands, may lead to impaired vitamin D
      status. The objectives of this study were to document vitamin D status and intake
      and assess the relationship between vitamin D status and SCD-related outcomes in
      Canadian children with SCD followed in a tertiary pediatric center. Our study
      population included 119 children (47% males, median age [interquartile range]:
      11.1 [9.2-14.8]) mainly of Haitian and Sub-Saharan African origin who had at
      least one measure of serum 25-hydroxyvitamin D (25OHD) performed between June
      2015 and February 2017. Predominant genotypes were homozygous hemoglobin S (60%)
      and sickle hemoglobin-C (32%). Vitamin D deficiency (25OHD<30 nmol/L) and
      insufficiency (30 to 49 nmol/L) were present in 31% and 37% of children,
      respectively. Vitamin D-sufficient children (25OHD>50 nmol/L) had higher
      hemoglobin levels, lower leukocyte, reticulocyte, and neutrophil counts, compared
      with vitamin D-deficient and insufficient children. Vitamin D intake was low and
      modestly correlated to serum 25OHD levels. Acute SCD complications in the
      preceding 2 years were not associated with vitamin D status in these children.

PMID- 30212420
TI  - Understanding Platelet Function in Microsurgical Arterial Anastomosis: The
      Charing Cross Clamp Technique.

PMID- 30212421
TI  - Reporting Time Horizons in Randomized Controlled Trials in Plastic Surgery: A
      Systematic Review.
AB  - BACKGROUND: Current guidelines for randomized controlled trial reporting do not
      require authors to justify their choice of time horizon. This is concerning, as
      the time horizon when an outcome is assessed has important implications for the
      interpretation of study results, and resources allocated to an investigation.
      Therefore, this study seeks to examine the standards of time horizon reporting in
      the plastic surgery literature. METHODS: This is a systematic review of plastic
      surgery randomized controlled trials published within the past 4 years. The
      MEDLINE database was searched to yield relevant studies. All studies included
      were English language, prospective, nonpharmaceutical randomized controlled
      trials, comparing two plastic surgical interventions. Studies were classified
      into plastic surgery domains, and information regarding study population, time
      horizon reporting, and justification of chosen time horizon, was extracted.
      RESULTS: The search retrieved 720 articles, of which 103 were eligible for
      inclusion. Time horizons were reported as either a standardized time point at
      which all patients were assessed, or a follow-up duration range, or were not
      reported at all. Although most studies (85.4 percent) reported a standardized
      time horizon, the majority (85.4 percent) failed to provide a valid justification
      to support their selection of time horizon. CONCLUSIONS: Clinical investigators
      failed to justify their choice of time horizon in the majority of published
      randomized controlled trials. To limit heterogeneity, time horizons for given
      interventions should be standardized to improve validity of outcome assessments,
      enable future pooling of results, and increase research efficiency.

PMID- 30212422
TI  - Compact and Economical Microsurgical Training Made Possible with Virtual Reality.

PMID- 30212423
TI  - Bladder Symptoms in Children With Functional Constipation: A Systematic Review.
AB  - OBJECTIVE: The aim of the review is to perform a systematic review of the
      literature examining the prevalence of bladder symptoms in children with
      functional constipation (FC) and to compare the prevalence of those symptoms
      between children with and without FC. METHODS: In this systematic review 4
      databases were searched to July 2018. Studies investigating the prevalence of
      bladder symptoms in children aged 4 to 17 years with FC were included. There was
      no language restriction. Two reviewers independently extracted data and assessed
      study quality. Clinical heterogeneity between studies was investigated.
      Prevalence rates of bladder symptoms in children with FC were calculated.
      Relative risks were calculated to compare the prevalence of bladder symptoms
      between children with and without FC. RESULTS: Among 23 studies of children with
      FC, 22 reported the prevalence bladder symptoms (12,281 children) and 7 reported
      the prevalence of urinary tract infections (UTIs) (687 children). The prevalence
      rates of single bladder symptoms, lower urinary tract symptoms (LUTS), and UTI
      varied between 2% to 47%, 37% to 64%, and 6% to 53%. The relative risks were 1.24
      to 6.73 for 20 single bladder symptoms (12 studies) and 2.18 to 6.55 for UTI (2
      studies). The 95% confidence intervals indicated significance in 14 of 20 single
      bladder symptoms. CONCLUSIONS: Bladder symptoms seem common in children with FC,
      but the reported prevalence varies greatly. Children with FC are more likely to
      have bladder symptoms than children without FC. We recommend that clinicians be
      aware of concomitant bladder symptoms in children presenting with FC.

PMID- 30212424
TI  - Impact of Licensed Federal Firearm Suppliers on Firearm-Related Mortality.
AB  - BACKGROUND: Legal firearm sales occur largely through suppliers that have Federal
      Firearm Licensees (FFLs). Since FFL density might reflect ease-of-access to
      firearm purchases, we hypothesized that the number of FFL dealers would be
      associated with firearm-related deaths. We further hypothesized that licensee
      type subsets would be associated with differential risks for gun-related deaths.
      METHODS: We used data from the National Center for Health Statistics National
      Vital Statistics System (2008-2014) and national data on Federal Firearms
      Licensees for 2014. Correlation analysis and linear regression analysis were
      performed to determine the relationship between different licensee types and
      firearm-related deaths. We controlled for population, number of statewide
      registered firearms, and the density of other types of FFLs. RESULTS: We
      identified a total of 65,297 FFLs. There was a moderate correlation (R = 0.53,
      rho = 0.48) between total FFL density and firearm-related death rates. Further
      analysis by type of firearm-related death showed a strong correlation (R = 0.81,
      rho = 0.76) between total FFL density and firearm-related suicide rates. No
      correlation was found between total FFL density and firearm-related homicide
      rate. Among individual FFL types, FFL02 (firearm dealing pawnshop) density was
      the only FFL-type found to be correlated with firearm-related death rates. We
      found a strong correlation between FFL02 density and overall firearm-related
      death rate (R = 0.69, rho = 0.78) and firearm-related suicide rate (R = 0.72, rho
      = 0.78). Linear regression analysis showed that even while controlling for number
      of registered firearms and population, the number of firearm-dealing pawnshops
      remained significantly associated with overall firearm-related deaths and firearm
      related suicides. CONCLUSION: Access to legally-distributed firearms is
      associated with firearm-related death rates, particularly firearm-related
      suicides. Specifically, firearm-dealing pawnshops were associated with suicide
      related deaths. These findings suggest that deeper exploration of legal firearm
      access and firearm-related injuries would benefit discussion of preventative
      measures. LEVEL OF EVIDENCE: IV TYPE OF STUDY: Prognostic and Epidemiological.

PMID- 30212425
TI  - Treatment of tibial deformities with the Fassier-Duval telescopic nail and
      minimally invasive percutaneous osteotomies in patients with osteogenesis
      imperfecta type III.
AB  - Osteogenesis imperfecta (OI) is a rare congenital osteodystrophy. Patients with
      OI present with osteoporosis, extreme bone fragility and severe deformities of
      the lower limbs, which predispose them to frequent fractures. The aim of our
      study is to describe the minimally invasive osteotomy technique to correct the
      tibial deformities in patients with OI type III, using the Fassier-Duval (FD)
      intramedullary nailing, which is considered the gold standard in this kind of
      surgery. We analyzed the results obtained from 14 patients with OI type III,
      treated for tibial deformities with the minimally invasive percutaneous osteotomy
      technique and osteosynthesis with the FD telescopic nail. The results were
      compared with that of a control group composed of 18 patients with OI type III,
      treated for tibial deformities with open technique osteotomies and osteosynthesis
      with FD telescopic nail. The follow-up was set at 18 months postoperatively. The
      data concerning the following were collected from the two groups: duration of
      surgery, number of osteotomies performed, postoperative pain, time required for
      functional recovery, and for the formation of bone callus. To analyze the
      variations in the quality of life, all the patients were given the Pediatric
      Outcomes Data Collection Instrument questionnaire, before surgery and at the end
      of the follow-up. In patients who underwent corrective surgery with the
      percutaneous technique, the average duration of surgery was inferior, the
      postoperative pain was significantly lower, the recovery of 90 degrees  range of
      motion of knee flexion was reached at an average of 37.8 days, and they ambulated
      bearing full weight on the leg without auxiliary aids on average 45 days after
      surgery. The Pediatric Outcomes Data Collection Instrument questionnaire values
      were satisfactory in both groups. The osteosynthesis with the FD telescopic nail,
      performed with the minimally invasive surgical technique, has improved the
      management of deformities in OI. The minimally invasive technique, however,
      requires the maturation of three distinct learning curves: surgery on patients
      with OI, open technique with the FD nail, and percutaneous technique with the FD
      nail.

PMID- 30212426
TI  - Multifocal Inflammatory Pseudotumor of the Temporal Bone, Maxillary Sinus, and
      Orbit.
AB  - OBJECTIVE: This is the first report of multifocal inflammatory pseudotumor (IPT)
      involving the temporal bone, orbit and paranasal sinus, and the use of rituximab
      as adjunctive therapy in multifocal temporal bone IPT. PATIENT: We describe a 46
      year-old man with orbital and maxillary sinus IPT, whose disease progressed
      despite radiation and steroid burst. He then developed contralateral mastoid
      disease, otalgia, aural fullness, and hearing loss. INTERVENTION: He was
      initiated on rituximab and prednisone therapy. Mastoidectomy with near-total
      tumor removal was accomplished and histopathology confirmed IPT. A literature
      review was also performed. MAIN OUTCOME MEASURE: Tumor regression or recurrence.
      RESULT: Despite disease progression after radiation and steroids, his orbital,
      sinus, and mastoid disease improved after surgery, steroids, and rituximab. A
      review of four other previously reported cases of multifocal disease involving
      the temporal bone suggest that multifocal disease may be a more aggressive entity
      with higher recurrence rate compared with solitary disease. Although surgery and
      steroids are typically recommended, there is currently no consensus treatment
      recommendation. CONCLUSIONS: Multifocal IPT of the temporal bone is a rare but
      aggressive entity for which surgery and steroid combination therapy should be
      first line treatment. We suggest rituximab may be an effective adjunctive
      treatment particularly for recurrent disease or where systemic therapy may be
      favored.

PMID- 30212427
TI  - Sudden Sensorineural Hearing Loss in Hemodialysis Patients Could be a Marker of
      Pathogenic Progression in the Mortality and Atherosclerotic Events: A National
      Cohort Study.
AB  - OBJECTIVES: There are higher incidence of sudden sensorineural hearing loss
      (SSHL) in hemodialysis (HD) patients than in the general population. Long-term
      outcomes of HD patients with new-onset SSHL have yet to be investigated although
      SSHL is considered as an independent risk of cardiovascular diseases in the
      general population. We examined the risks of mortality and atherosclerotic events
      in HD patients with new-onset SSHL in Taiwan. STUDY DESIGN: Cohort study.
      METHODS: Using the Taiwan National Health Institutes Research Database, 105,243
      HD patients were identified between 1997 and 2008. In total, 288 HD patients with
      a new diagnosis of idiopathic SSHL were enrolled and matched with 1,728 HD
      patients without SSHL by using propensity score matching at a ratio of 1:6. MAIN
      OUTCOME MEASURES: A multivariate Cox regression and a competing risk regression
      were used to evaluate mortality and atherosclerotic events. RESULTS: Results
      revealed a risk of mortality in HD patients with SSHL than in HD patients without
      SSHL (adjusted hazard ratios [aHRs] 2.22, 95% confidence interval [CI] 1.71
      2.89). HD patients with SSHL had higher risks of hemorrhagic stroke (competing
      risk aHR 4.08, 95% CI 1.93-8.61), ischemic stroke (competing risk aHR 2.34, 95%
      CI 1.45-3.78), acute coronary syndrome, and peripheral arterial occlusive disease
      than did the HD patients without SSHL. CONCLUSION: This study is the first to
      signify that the risks of mortality and atherosclerotic complications in HD
      patients with new-onset SSHL are increased. Therefore, we should pay attention to
      risks of mortality and atherosclerotic events in HD patients with new-onset SSHL.

PMID- 30212428
TI  - Cholesteatoma of the External Auditory Canal: Review of Staging and Surgical
      Strategy.
AB  - INTRODUCTION: External auditory canal cholesteatomas (EACC) is insidious in
      nature and rare entity. There are only few case series on EACCs and surgical
      strategy is not standardized. OBJECTIVES: 1) To elucidate etiology of EACC and
      cardinal features. 2) To suggest a practical staging of EACC. 3) To enumerate
      surgical management according to stage of EACC. STUDY DESIGN: Retrospective study
      in a quaternary referral center of 31 consecutive cases of EACC. RESULTS: Thirty
      one patients with EACC were reviewed. Unilateral otorrhea 19 (61.2%), hearing
      loss 22 (70.9%), and otalgia 8 (25.8%) are cardinal symptoms. Sixteen primary and
      15 secondary EACCs were treated. Bone erosion was observed in 20 cases. In the
      present series, stage III = 12 (38.7%), stage II = 8 (25.8%), stage I = 11
      (35.4%) underwent definitive treatment by surgery. Canalplasty with
      reconstruction was done in 19 cases of stages I and II. Of 12 cases in stage III,
      3 cases underwent canalplasty with reconstruction. Subtotal petrosectomy was done
      in five cases. Intact canal wall mastoidectomy with canalplasty in two cases and
      radical mastoidectomy in two cases. Fascia, cartilage, muscle, and bone dust were
      used for reconstruction. Median follow-up period was 6 years and no recurrence of
      cholesteatoma was observed. CONCLUSION: EACC is unique entity. Intraoperative and
      radiological findings assist in correct and practical staging of EACC. Late stage
      presentations of EACC are common. Definitive surgical treatment in our series
      avoided recurrence of cholesteatoma.

PMID- 30212429
TI  - The Medial Canthus Reference Electrode Is not Electrically Indifferent to the
      Ocular Vestibular Evoked Myogenic Potential.
AB  - OBJECTIVE: To determine whether a reference electrode placed over the
      contralateral medical canthus is electrically indifferent to the ocular
      vestibular evoked myogenic potential (oVEMP). STUDY DESIGN: Prospective
      observational study. SETTING: Tertiary academic center. PARTICIPANTS: Nineteen
      otologically normal subjects. METHODS: oVEMPs were recorded using a 500 Hz tone
      burst at 125 dB pSPL using both a conventional dual infra-orbital derivation and
      contralateral infraorbital electrode referenced to a medial canthus electrode
      known as the "belly-tendon" derivation. RESULTS: The belly-tendon derivation
      produced significantly larger oVEMP amplitudes. This appears to be due to a
      polarity inversion of the first negative peak that occurs when the reference
      electrode is placed over the medial canthus. Thus, the belly-tendon derivation
      was associated with reference contamination, but in this instance the reference
      contamination produced an augmented oVEMP amplitude. CONCLUSIONS: Neither the
      dual infra-orbital nor belly-tendon electrode montages are electrically neutral.
      Reference contamination is the source of both a decrease in amplitude using
      conventional recording techniques and increased amplitude using the belly-tendon
      montage. The results support the contention that the belly-tendon montage
      generates a reversed polarity response, i.e., algebraically subtracted (i.e.,
      added in the differential amplifier) from the response recorded at the
      infraorbital midline enhancing the oVEMP amplitude. It should be noted that the
      amplitude gained when using the belly-tendon montage may also be due to
      electromyographic (EMG) generated by extraocular muscles other than the inferior
      oblique generator, resulting in a loss of specificity. The authors recommend the
      belly-tendon montage be used in clinical situations where the oVEMP is absent or
      low in amplitude.

PMID- 30212430
TI  - 25 years and sex is still hot.

PMID- 30212431
TI  - Fractional microablative CO2 laser in breast cancer survivors affected by
      iatrogenic vulvovaginal atrophy after failure of nonestrogenic local treatments:
      a retrospective study: Erratum.

PMID- 30212433
TI  - Racial and Ethnic Differences in Viral Suppression Among HIV-Positive Women in
      Care.
AB  - BACKGROUND: Women with HIV diagnoses are less likely to be virally suppressed
      than men. Women of different racial/ethnic groups may be differentially affected
      by sociodemographic factors. We examined differences in viral suppression among
      women by race/ethnicity and associated variables to inform prevention
      interventions. METHODS: We used data from the 2010-2014 cycles of the Medical
      Monitoring Project, a cross-sectional survey of HIV-positive adults in care. We
      limited analyses to black, Hispanic, and white women. We calculated weighted
      prevalences of recent viral suppression (undetectable or <200 copies/mL) and
      sustained viral suppression (consistent viral suppression during the past 12
      months) among women by race/ethnicity. We computed adjusted prevalence
      differences (aPDs) and 95% confidence intervals (CIs) for viral suppression by
      racial/ethnic group, controlling for selected variables, including available
      social determinants of health variables. RESULTS: Among women, 62.9% were black,
      19.8% Hispanic, and 17.3% white. Overall, 74.3% had recent viral suppression, and
      62.3% had sustained viral suppression. Compared with white women (79.7%, CI: 77.2
      to 82.2), black (72.5%, CI: 70.3 to 74.7; PD: 7.2) and Hispanic (75.4%, CI: 72.6
      to 78.3; PD: 4.3) women were less likely to have recent viral suppression. In
      multivariable analyses, after adjusting for antiretroviral therapy adherence, HIV
      disease stage, age, homelessness, and education, black-white aPDs remained
      significant for recent (aPD: 4.8, CI: 1.6 to 8.1) and sustained (aPD: 5.0, CI:
      1.1 to 9.0) viral suppression. CONCLUSION: Viral suppression was suboptimal for
      all women, but more for black and Hispanic women. Differences between black,
      Hispanic, and white women may be partially due to antiretroviral therapy
      adherence, HIV disease stage, and social determinants of health factors.

PMID- 30212432
TI  - Human Immunodeficiency Virus Infection Increases the Risk of Incident Uveitis
      Among People Living With HIV/AIDS.
AB  - BACKGROUND: Case reports indicated that HIV itself may be a direct cause of
      uveitis. However, the association of HIV with incident uveitis has not been
      extensively studied. This nationwide cohort study determined the association of
      HIV with incident uveitis. METHODS: Since January 1, 2003, we identified adult
      people living with HIV/AIDS (PLWHA) from Taiwan Centers for Disease Control HIV
      Surveillance Database. A control cohort without HIV infection, matched for age
      and sex, was selected for comparison from the Taiwan National Health Insurance
      Research Database. The time-dependent Cox proportional hazards model was used to
      determine the associations of HIV and highly active antiretroviral therapy
      (HAART) with incident uveitis, while considering death as a competing risk event.
      RESULTS: Of the total 120,430 patients (24,086 PLWHA and 96,344 matched
      controls), 609 (0.51%) had incident uveitis, including 334 (1.39%) PLWHA and 265
      (0.28%) controls. After adjusting for age, sex, and comorbidities, HIV infection
      was found to be an independent risk factor for incident uveitis [adjusted hazard
      ratio (AHR), 5.55; 95% confidence interval (CI): 4.67 to 6.59]. Within PLWHA, the
      risk of incident uveitis was significantly higher in those who received HAART
      (AHR, 2.46; 95% CI: 1.71 to 3.54). In addition, considering the short- and long
      term effects of HAART on incident uveitis, HAART was found to associate with a
      higher risk of uveitis development within 1 year of treatment (AHR, 3.36; 95% CI:
      2.41 to 4.69), but not after 1 year of HAART initiation (AHR, 1.14; 95% CI: 0.76
      to 1.72). CONCLUSIONS: HIV infection is an independent risk factor for incident
      uveitis.

PMID- 30212434
TI  - Is on-Demand HIV Pre-exposure Prophylaxis a Suitable Tool for Men Who Have Sex
      With Men Who Practice Chemsex? Results From a Substudy of the ANRS-IPERGAY Trial.
AB  - BACKGROUND: Chemsex-the use of psychoactive substances during sexual encounters
      among men who have sex with men is a growing concern. On-demand HIV pre-exposure
      prophylaxis (PrEP) may be a suitable tool to prevent HIV transmission among
      "chemsexers." We used the open-label extension study of the ANRS-IPERGAY trial to
      describe chemsexers and their PrEP use. METHODS: Among the 361 men who have sex
      with men enrolled in ANRS-IPERGAY's open-label extension study, we selected the
      331 with available data on drug use. A 2-monthly web questionnaire on
      sociobehavioral data was used to compare sexual behaviors between questionnaires
      where chemsex was reported and those where it was not. Using a generalized
      estimating equation logistic regression, we studied whether practicing chemsex
      was associated with correct PrEP use. RESULTS: Among the 331 participants, 30%
      reported chemsex practice at least once during follow-up and were considered
      chemsexers. Chemsex was reported in 16% of all questionnaires. Chemsexers were
      not significantly different from nonchemsexers regarding sociodemographic
      characteristics, although they reported greater use of anxiolytics and more
      sensation-seeking. Reporting chemsex was associated with more high-risk sexual
      practices and a higher perception of risk. After adjustment for other potential
      correlates, chemsex remained associated with correct PrEP use [odds ratio (95%
      confidence interval) = 2.24 (1.37 to 3.66)]. CONCLUSIONS: Our findings show that
      chemsexers were more likely to report high-risk sexual practices but also had a
      higher perception of risk. They were also more likely to use PrEP correctly when
      practicing chemsex. Consequently, PrEP may be a suitable tool to reduce HIV-risk
      transmission among chemsexers.

PMID- 30212435
TI  - Self-management Interventions for Pain and Physical Symptoms Among People Living
      With HIV: A Systematic Review of the Evidence.
AB  - INTRODUCTION: Pain and symptoms still persist among people living with HIV/AIDS.
      Evidence-based self-management interventions have the potential to help people
      with HIV/AIDS to successfully manage pain and symptoms. We aimed to identify and
      appraise the evidence regarding the effectiveness of self-management
      interventions for pain and/or physical symptoms in people living with HIV/AIDS.
      METHODS: We searched for controlled intervention studies in Amed, Assian, CINAHL,
      Cochrane Library, Embase, Medline, PsycInfo, Scopus, and Web of Science data
      bases, from 1984 to February 2017. Two reviewers screened and extracted data,
      assessed risk of bias (using Joanna Briggs Institute Critical Appraisal checklist
      for randomized and nonrandomized trials), and rated the quality of evidence
      (GRADE tool). RESULTS: We identified 22 original papers reporting 19 different
      studies. Of these, 17 used randomized controlled trial designs. Three studies
      reported data on pain severity, and 2 studies reported data on pain interference
      outcomes with one study reporting positive effect on both outcomes. Outcomes for
      physical symptoms were reported in 13 studies with 6 studies reporting positive
      effect. The quality of evidence was moderate for pain outcomes. For physical
      symptoms, one study was rated as moderate; the rest were rated as low n = 8 and
      very low n = 4 quality. CONCLUSIONS: There is some evidence to suggest that self
      management interventions delivered either online, face-to-face, or group-based
      consisting of booklet, leaflet, or manuals are effective in improving pain and
      physical symptoms. Findings suggest the need for theoretically plausible high
      quality clinical trials of pain and physical symptom self-management among
      culturally diverse people with HIV.

PMID- 30212437
TI  - Brief Report: Antimalarial Benefit of HIV Antiretroviral Therapy in Areas of Low
      to Moderate Malaria Transmission Intensity.
AB  - BACKGROUND: We previously used mathematical modeling to predict reduced malaria
      incidence in children with protease inhibitor (PI)-, compared with nonnucleoside
      reverse transcriptase inhibitor-, based highly active antiretroviral therapy
      (HAART), in moderate to high malaria transmission areas. These effects were
      accounted for, in part, by pharmacokinetic (PK) interactions between PIs and
      artemether-lumefantrine (AL). OBJECTIVE: Because of potentially reduced malaria
      transmission reservoirs in HIV-infected children due to PI/AL PK interactions
      impacting non-HIV-infected children, we estimate the antimalarial benefit of PI
      based HAART in all children, and in HIV-infected children only residing in low to
      moderate malaria transmission areas. DESIGN: A dynamic model of malaria
      transmission was developed to evaluate the PK interaction of PI-based HAART with
      the antimalarial, AL for preventing malaria. METHODS: To evaluate the benefit of
      HIV PI-based HAART on malaria incidence, a malaria transmission model with
      varying degrees of HIV newborn prevalence was developed using recent pediatric
      clinical trial data in Lilongwe, Malawi. RESULTS: Comparing situations of low to
      high HIV newborn prevalence, and low to moderate malaria transmission
      intensities, our model predicts the combination of PI-based HAART with AL-treated
      malaria prevents 0.04-24.8 and 0.05-34.5 annual incidences of malaria overall per
      1000 children, and saves 0.003-1.66 and 0.003-2.30 disability-adjusted life years
      per 1000 children, respectively. When incorporating seasonality, 0.01-7.3 and
      0.01-5.9 annual incidences of malaria overall per 1000 children, and 0.0-0.5 and
      0.001-0.41 disability-adjusted life years per 100 children, are prevented,
      respectively. CONCLUSIONS: In low to moderate malaria transmission intensity
      areas, PI-based HAART may reduce malaria events in children when AL is used.

PMID- 30212436
TI  - Brief Report: Safety and Tolerability of Inguinal Lymph Node Biopsy in
      Individuals With Acute HIV Infection in Thailand.
AB  - INTRODUCTION: Latent HIV reservoirs are rapidly established in lymphoid tissues
      during acute HIV infection (AHI). Sampling these tissues provides important
      information about HIV pathogenesis. This period is associated with viral
      replication and immune activation that may affect procedure-related adverse
      events (AEs). We examined the safety and tolerability of inguinal lymph node (LN)
      biopsy in research participants with AHI in Bangkok, Thailand. METHODS: Between
      2013 and 2016, 67 AHI participants in the RV254/SEARCH010 study underwent at
      least one optional inguinal LN biopsy during AHI at the baseline visit and/or
      after antiretroviral therapy (median 48 weeks after antiretroviral therapy).
      Biopsy-related AEs were graded according to NIH Division of AIDS guidelines.
      Poisson regression was used to calculate incidence rate ratios and 95% confidence
      intervals to evaluate associations of demographic and HIV characteristics,
      procedure timing, and repetition with AE incidence. RESULTS: Of the 67
      participants, 97% were male with a median age of 26. Among 78 LN biopsies (39 at
      baseline and 39 at follow-up), 10 (12.8%) AEs were reported: 6 (7.7%) grade 1 and
      4 (5.1%) grade 2. The AEs were biopsy-site discomfort (n = 8, 10.2%) and hematoma
      (n = 2, 2.6%). No factors were significantly associated with AE incidence. All
      biopsy-related AEs were transient and self-limited. CONCLUSIONS: Inguinal LN
      biopsies were safe and well tolerated in mostly Thai men with AHI. As LN biopsies
      become an integral part of HIV research, this study provides information to
      participants, researchers, and institutional review boards that these samples can
      be safely obtained.

PMID- 30212438
TI  - Integrated Treatment for Smoking Cessation, Anxiety, and Depressed Mood in People
      Living With HIV: A Randomized Controlled Trial.
AB  - OBJECTIVE: Among people living with HIV, cigarette smoking rates are higher than
      among the general population, and anxiety, depression, and their disorders are
      common and associated with smoking and poorer outcomes during cessation. This
      study evaluated the efficacy of an integrated smoking cessation intervention,
      developed to target anxiety, depression, and smoking cessation concurrently among
      people living with HIV. METHOD: Smokers living with HIV who reported at least
      moderate motivation to quit smoking were randomized into a novel 9-week
      integrated intervention (QUIT), consisting of 1 psychoeducation
      (prerandomization) session and 9 weekly 1-hour sessions of cognitive behavioral
      therapy for smoking cessation and anxiety/depression plus nicotine replacement
      therapy, or a 9-week enhanced standard smoking intervention (ETAU), consisting of
      1 psychoeducation session (prerandomization) and 4 brief weekly check-in sessions
      plus nicotine replacement therapy. All were instructed to make a quit attempt at
      week 6. RESULTS: Seventy-two participants were enrolled, and 53 were randomized.
      41/53 participants completed the active treatment phase of the study. 7-day point
      prevalence abstinence, verified with expired carbon monoxide, was significantly
      higher among those in the integrated intervention than those in the enhanced
      standard intervention both end-of-treatment {[MQUIT = 59%, METAU = 9%; b = 5.60,
      95% confidence interval: (2.64 to 8.56), t(332) = 3.72, P < 0.001]} and 6-months
      post-quit date {[MQUIT = 46%, METAU = 5%; b = 7.69, 95% confidence interval:
      (4.60 to 10.78), t(332) = 4.90, P < 0.001]}. Consideration of patterns of
      missingness did not alter the significance of these findings. CONCLUSIONS: The
      integrated intervention was associated with substantially higher short-term and
      long-term abstinence rates than the enhanced standard intervention. These data
      provide promising initial evidence supporting the benefits of an integrated
      anxiety-depression/smoking cessation program specifically tailored for people
      living with HIV.

PMID- 30212439
TI  - HIV Status Is a Greater Determinant of Low Self-perceived Life Expectancy Than
      Cigarette Smoking in a Well-resourced Setting.

PMID- 30212440
TI  - Plasma Resistin Levels in Patients with Acute Aortic Dissection: A Propensity
      Score-Matched Observational Case-Control Study.
AB  - BACKGROUND The aim of this observational case-control study was to compare the
      levels of plasma resistin between patients with acute aortic dissection and
      matched controls, and to use propensity score matching (PSM) to reduce case
      selection bias and clinical confounders. MATERIAL AND METHODS With the use of
      PSM, this study included 43 pairs of patients with acute aortic dissection (type
      A and type-B dissection) and matched controls. Plasma resistin levels and other
      laboratory parameters were compared between the two groups, including white blood
      cell (WBC) count, glucose, high sensitivity C-reactive protein (hs-CRP),
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and D-dimer. The
      correlations between resistin and other laboratory parameters were evaluated in
      patients with acute aortic dissection. RESULTS Following PSM adjustment for
      clinical variables, including age, sex, body mass index, smoking, alcohol
      drinking, hypertension, diabetes mellitus, coronary heart disease and stroke,
      plasma resistin levels were significantly increased in patients with acute aortic
      dissection when compared with controls (35.2+/-13.8 vs. 18.4+/-9.1 ng/ml)
      (p<0.001). WBC counts, and levels of glucose, hs-CRP, IL-6, TNF-alpha and D-dimer
      were also significantly increased in the patients with aortic dissection compared
      with the control group. After adjustment for these variables, the association
      between plasma resistin levels and acute aortic dissection remained significant
      (OR, 1.114; 95% CI, 1.036-1.224) (p<0.001). Plasma resistin levels was positively
      correlated with WBC count (r=0.368, p=0.015), hs-CRP (r=0.359, p=0.022), IL-6
      (r=0.306, p=0.046) and TNF-alpha levels (r=0.315, p=0.040) in patients with acute
      aortic dissection. CONCLUSIONS Acute aortic dissection is associated with
      elevated levels of plasma resistin and other pro-inflammatory cytokines. Plasma
      resistin levels is positively associated with other pro-inflammatory cytokines in
      acute aortic dissection.

PMID- 30212441
TI  - Notes from the Field: Enterovirus A71 Neurologic Disease in Children - Colorado,
      2018.

PMID- 30212442
TI  - Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults - United
      States, 2016.
AB  - Chronic pain, one of the most common reasons adults seek medical care (1), has
      been linked to restrictions in mobility and daily activities (2,3), dependence on
      opioids (4), anxiety and depression (2), and poor perceived health or reduced
      quality of life (2,3). Population-based estimates of chronic pain among U.S.
      adults range from 11% to 40% (5), with considerable population subgroup
      variation. As a result, the 2016 National Pain Strategy called for more precise
      prevalence estimates of chronic pain and high-impact chronic pain (i.e., chronic
      pain that frequently limits life or work activities) to reliably establish the
      prevalence of chronic pain and aid in the development and implementation of
      population-wide pain interventions (5). National estimates of high-impact chronic
      pain can help differentiate persons with limitations in major life domains,
      including work, social, recreational, and self-care activities from those who
      maintain normal life activities despite chronic pain, providing a better
      understanding of the population in need of pain services. To estimate the
      prevalence of chronic pain and high-impact chronic pain in the United States, CDC
      analyzed 2016 National Health Interview Survey (NHIS) data. An estimated 20.4%
      (50.0 million) of U.S. adults had chronic pain and 8.0% of U.S. adults (19.6
      million) had high-impact chronic pain, with higher prevalences of both chronic
      pain and high-impact chronic pain reported among women, older adults, previously
      but not currently employed adults, adults living in poverty, adults with public
      health insurance, and rural residents. These findings could be used to target
      pain management interventions.

PMID- 30212444
TI  - QuickStats: Age-Adjusted Death Rates* for Lung Cancer,? by Urbanization of County
      of ResidenceS - National Vital Statistics System, United States, 2006 and 2016.

PMID- 30212443
TI  - Sentinel Surveillance for Congenital Rubella Syndrome - India, 2016-2017.
AB  - Rubella infection during pregnancy can result in miscarriage, fetal death,
      stillbirth, or a constellation of congenital malformations known as congenital
      rubella syndrome (CRS). The 11 countries in the World Health Organization (WHO)
      South-East Asia Region are committed to the elimination of measles and control of
      rubella and CRS by 2020. Until 2016, when the Government of India's Ministry of
      Health and Family Welfare and the Indian Council of Medical Research initiated
      surveillance for CRS in five sentinel sites, India did not conduct systematic
      surveillance for CRS. During the first 8 months of surveillance, 207 patients
      with suspected CRS were identified. Based on clinical details and serologic
      investigations, 72 (34.8%) cases were classified as laboratory-confirmed CRS,
      four (1.9%) as congenital rubella infection, 11 (5.3%) as clinically compatible
      cases, and 120 (58.0%) were excluded as noncases. The experience gained during
      the first phase of surveillance will be useful in expanding the surveillance
      network, and data from the surveillance network will be used to help monitor
      progress toward control of rubella and CRS in India.

PMID- 30212445
TI  - Notes from the Field: Mumps Outbreak Associated with Cheerleading Competitions -
      North Texas, December 2016-February 2017.

PMID- 30212446
TI  - Sexual Risk Behavior Differences Among Sexual Minority High School Students -
      United States, 2015 and 2017.
AB  - Sexual minority youths (i.e., those identifying as gay, lesbian, bisexual, or
      another nonheterosexual identity or reporting same-sex attraction or sexual
      partners) are at higher risk than youths who are not sexual minority youth
      (nonsexual minority youth) for negative health behaviors and outcomes, including
      human immunodeficiency virus (HIV) infection, other sexually transmitted diseases
      (STDs), pregnancy (1),* and related sexual risk behaviors (2). Less is known
      about sexual risk behavior differences between sexual minority youth subgroups.
      This is the first analysis of subgroup differences among sexual minority youths
      using nationally representative Youth Risk Behavior Survey (YRBS) data. CDC
      analyzed pooled data from the 2015 and 2017 cycles of the national YRBS, a cross
      sectional, school-based survey assessing health behaviors among U.S. students in
      grades 9-12. Analyses examined differences in eight sexual risk behaviors between
      subgroups of sexual minority youths and nonsexual minority youths, as well as
      within sexual minority youths. Logistic regression models controlling for
      race/ethnicity and grade found that bisexual females and "not sure" males
      reported higher prevalences for many behaviors than did heterosexual students.
      For behavior-based subgroups, the largest number of differences were seen between
      students who had sexual contact with both sexes compared with students with only
      opposite-sex sexual contact. Findings highlight subgroup differences within
      sexual minority youths that could inform interventions to promote healthy
      behavior.

PMID- 30212447
TI  - Erratum: Vol. 65, No. 15.

PMID- 30212448
TI  - Refined RIP-seq protocol for epitranscriptome analysis with low input materials.
AB  - N6-Methyladenosine (m6A) accounts for approximately 0.2% to 0.6% of all adenosine
      in mammalian mRNA, representing the most abundant internal mRNA modifications.
      m6A RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq) is
      a powerful technique to map the m6A location transcriptome-wide. However, this
      method typically requires 300 MUg of total RNA, which limits its application to
      patient tumors. In this study, we present a refined m6A MeRIP-seq protocol and
      analysis pipeline that can be applied to profile low-input RNA samples from
      patient tumors. We optimized the key parameters of m6A MeRIP-seq, including the
      starting amount of RNA, RNA fragmentation, antibody selection, MeRIP
      washing/elution conditions, methods for RNA library construction, and the
      bioinformatics analysis pipeline. With the optimized immunoprecipitation (IP)
      conditions and a postamplification rRNA depletion strategy, we were able to
      profile the m6A epitranscriptome using 500 ng of total RNA. We identified
      approximately 12,000 m6A peaks with a high signal-to-noise (S/N) ratio from 2
      lung adenocarcinoma (ADC) patient tumors. Through integrative analysis of the
      transcriptome, m6A epitranscriptome, and proteome data in the same patient
      tumors, we identified dynamics at the m6A level that account for the discordance
      between mRNA and protein levels in these tumors. The refined m6A MeRIP-seq method
      is suitable for m6A epitranscriptome profiling in a limited amount of patient
      tumors, setting the ground for unraveling the dynamics of the m6A
      epitranscriptome and the underlying mechanisms in clinical settings.

PMID- 30212450
TI  - Misconceptions and paradoxes in soil-transmitted helminthiases control as a
      public health problem.
AB  - Soil-transmitted helminthiases (STHs) constitute a public health problem that
      requires immediate action to resolve the morbidity of those harboring the
      parasites in their guts, to prevent infection in all those at risk, and to
      interrupt the vicious circle of poverty and disease in the affected communities,
      structural poverty being the main determinant of this group of infectious
      diseases. Since the times of the Rockefeller initiatives over a hundred years
      ago, the strategy has been viewed as one requiring community-wide efforts rather
      than pure individual case management. The World Health Organization (WHO) and its
      regional offices, as the governing institutions endorsed by the countries and
      their governments, have been the leaders in stating the actual executive measures
      to reach the goals and endpoints for the management of the problem. With the task
      of setting a group of activities that could be launched, monitored, and measured,
      these actions were established with the available resources since this public
      health problem had to be launched immediately, resources were those available at
      the moment and not those appearing on a wish list. Considerable progress has been
      made in the establishment of policies for the achievement of the Millennium
      Development Goals (MDGs), later followed by the Sustainable Development Goals
      (SDGs) through WHO-lead actions for the control of neglected tropical diseases
      (NTDs). With an initial goal of morbidity control, there are already discussions
      and proposals for elimination of STH if support is sustained and empiric facts
      confirm data emerging from modeling and small-scale studies. The aim of these
      comments is to describe and question instances of currently accepted concepts,
      theories, and practices that conform to the dogmatic status quo that serves as
      the foundation on top of which the new elimination aspirations are supposed to be
      built on, which might not be serving the desired purpose if taken unrevised.

PMID- 30212449
TI  - Structure and function of archaeal histones.
AB  - The genomes of all organisms throughout the tree of life are compacted and
      organized in chromatin by association of chromatin proteins. Eukaryotic genomes
      encode histones, which are assembled on the genome into octamers, yielding
      nucleosomes. Post-translational modifications of the histones, which occur mostly
      on their N-terminal tails, define the functional state of chromatin. Like
      eukaryotes, most archaeal genomes encode histones, which are believed to be
      involved in the compaction and organization of their genomes. Instead of discrete
      multimers, in vivo data suggest assembly of "nucleosomes" of variable size,
      consisting of multiples of dimers, which are able to induce repression of
      transcription. Based on these data and a model derived from X-ray
      crystallography, it was recently proposed that archaeal histones assemble on DNA
      into "endless" hypernucleosomes. In this review, we discuss the amino acid
      determinants of hypernucleosome formation and highlight differences with the
      canonical eukaryotic octamer. We identify archaeal histones differing from the
      consensus, which are expected to be unable to assemble into hypernucleosomes.
      Finally, we identify atypical archaeal histones with short N- or C-terminal
      extensions and C-terminal tails similar to the tails of eukaryotic histones,
      which are subject to post-translational modification. Based on the expected
      characteristics of these archaeal histones, we discuss possibilities of
      involvement of histones in archaeal transcription regulation.

PMID- 30212452
TI  - Exemplar-based image completion using image depth information.
AB  - Image completion techniques are required to complete missing regions in digital
      images. A key challenge for image completion is keeping consistency of image
      structures without ambiguity and visual artifacts. We propose a novel method for
      image completion using image depth cue. Our method includes three major features.
      First, we compute the image gradient to improve image completion when searching
      for the most similar patches. Second, using image depth, we guide image
      completion by means of appropriate scale transformation. Third, we propose a
      global optimization patch-based method having gradient and depth features for
      image completion. Experiments demonstrate that our approach is a potentially
      superior method for completing missing regions.

PMID- 30212451
TI  - Isolation of pathogenic Leptospira strains from naturally infected cattle in
      Uruguay reveals high serovar diversity, and uncovers a relevant risk for human
      leptospirosis.
AB  - Leptospirosis is a neglected zoonosis with worldwide distribution. The causative
      agents are spirochete bacteria of the Leptospira genus, displaying huge diversity
      of serovars, the identity of which is critical for effective diagnosis and
      vaccination purposes. Among many other mammalian species, Leptospira infects
      cattle, eliciting acute signs in calves, and chronic disease in adult animals
      often leading to abortions. In South America, and including in Uruguay, beef and
      dairy export are leading sources of national income. Despite the importance of
      bovine health, food safety, and bovine-related dissemination of leptospirosis to
      humans, extremely limited information is available as to the identity of
      Leptospira species and serovars infecting cattle in Uruguay and the South
      American subcontinent. Here we report a multicentric 3-year study resulting in
      the isolation and detailed characterization of 40 strains of Leptospira spp.
      obtained from infected cattle. Combined serologic and molecular typing identified
      these isolates as L. interrogans serogroup Pomona serovar Kennewicki (20
      strains), L. interrogans serogroup Canicola serovar Canicola (1 strain), L.
      borgpetersenii serogroup Sejroe serovar Hardjo (10 strains) and L. noguchii (9
      strains). The latter showed remarkable phenotypic and genetic variability,
      belonging to 6 distinct serogroups, including 3 that did not react with a large
      panel of reference serogrouping antisera. Approximately 20% of cattle sampled in
      the field were found to be shedding pathogenic Leptospira in their urine,
      uncovering a threat for public health that is being largely neglected. The two L.
      interrogans serovars that we isolated from cattle displayed identical genetic
      signatures to those of human isolates that had previously been obtained from
      leptospirosis patients. This report of local Leptospira strains shall improve
      diagnostic tools and the understanding of leptospirosis epidemiology in South
      America. These strains could also be used as new components within bacterin
      vaccines to protect against the pathogenic Leptospira strains that are actually
      circulating, a direct measure to reduce the risk of human leptospirosis.

PMID- 30212454
TI  - Correction: Genome Sequence of the Pea Aphid Acyrthosiphon pisum.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.1000313.].

PMID- 30212453
TI  - Latent tuberculosis infection is associated with increased unstimulated levels of
      interferon-gamma in Lima, Peru.
AB  - BACKGROUND: We previously reported increased unstimulated blood levels of
      interferon-gamma in persons with latent tuberculosis infection (LTBI) in the
      United States, suggesting enhanced immune activation in LTBI. To investigate this
      further in a TB-endemic setting, we assessed interferon-gamma levels in persons
      with and without LTBI in Peru. METHODS: We analyzed data from patients with and
      without a recent type 1 (spontaneous) acute myocardial infarction (AMI) who were
      enrolled from two public hospital networks in Lima, Peru, and underwent LTBI
      testing using the QuantiFERON(r) TB Gold In-tube (QFT) assay. Participants with a
      positive QFT test were defined as having LTBI, whereas participants with a
      negative QFT test were defined as non-LTBI. Unstimulated interferon-gamma was
      quantified via enzyme-linked immunosorbent assay in the QFT nil-tube, which does
      not contain antigens. We compared unstimulated interferon-gamma levels between
      LTBI and non-LTBI groups using the Wilcoxon rank sum test. We used proportional
      odds modeling for multivariable analysis. RESULTS: Data from 214 participants
      were included in this analysis. Of those, 120 (56%) had LTBI. There were no
      significant differences in age, sex and comorbidities between LTBI and non-LTBI
      participants, except for recent AMI that was more frequent in LTBI. LTBI
      participants had higher unstimulated interferon-gamma levels compared to non-LTBI
      participants (median, interquartile range; 14 pg/mL, 6.5-52.8 vs. 6.5 pg/mL, 4.5
      15; P<0.01). LTBI remained associated with higher unstimulated interferon-gamma
      levels after controlling for age, sex, recent AMI, history of hypertension,
      diabetes mellitus, dyslipidemia, end stage renal disease, malignancy, obesity,
      and tobacco use (adjusted odds ratio, 2.93; 95% confidence interval, 1.8-4.9). In
      a sensitivity analysis that excluded participants with AMI, the association
      between unstimulated interferon-gamma and LTBI remained present (adjusted odds
      ratio; 3.93; 95% confidence interval, 1.9-8.2). CONCLUSIONS: LTBI was associated
      with higher unstimulated interferon-gamma levels. These data suggest ongoing
      immune activation in LTBI.

PMID- 30212455
TI  - Clinical usefulness of the angle between left main coronary artery and left
      anterior descending coronary artery for the evaluation of obstructive coronary
      artery disease.
AB  - BACKGROUND: A wider angle between the left anterior descending coronary artery
      (LAD) and left circumflex coronary artery (LCX) has been suggested to induce
      plaque formation in the arterial system via changes in shear stress. However, the
      relationship between the left main coronary artery (LM)-LAD angle and LAD
      stenosis has not been investigated. Therefore, we aimed to evaluate the
      associations between the LM-LAD and LAD-LCX angles and LAD stenosis. METHODS:
      Coronary computed tomography angiographies (CTAs) of 201 patients with suspected
      coronary artery disease were analyzed. Angle measurements were performed twice by
      experts using CTA images, and the values were averaged. The patients were divided
      into two groups, based on the presence of significant LAD stenosis (luminal
      diameter narrowing >=50%) on CTA. RESULTS: The mean LM-LAD and LAD-LCX angles
      were 37.46 degrees  and 63.04 degrees , respectively. The LM-LAD and LAD-LCX
      angles of the group with significant LAD stenosis were significantly wider than
      that of the group with nonsignificant LAD stenosis (P<0.001; P = 0.020,
      respectively). In a multivariate analysis, an LAD-LCX angle greater than 60
      degrees  showed a trend toward predicting significant LAD stenosis (HR, 3.14; 95%
      CI: 0.96-1026; P = 0.058). In contrast, an LM-LAD angle greater than 40 degrees 
      was a significant predictor of significant LAD stenosis (HR, 12.2; 95% CI: 2.60
      56.52; P = 0.001). CONCLUSIONS: The results of the present study may suggest that
      a wider LM-LAD angle could be used to identify patients at higher risk for
      coronary artery disease (CAD). Thus, close follow-up and preventive management of
      other risk factors may be needed in such cases.

PMID- 30212458
TI  - Cross-national comparison of gender differences in the enrollment in and
      completion of science, technology, engineering, and mathematics Massive Open
      Online Courses.
AB  - Massive Open Online Courses (MOOCs) have the potential to democratize education
      by providing learners with access to high-quality free online courses. However,
      evidence supporting this democratization across countries is limited. We explored
      the question of MOOC democratization by conducting cross-national comparisons of
      gender differences in the enrollment in and completion of science, technology,
      engineering, and mathematics (STEM) MOOCs. We found that while females were less
      likely than males to enroll in STEM MOOCs, they were equally likely to complete
      them. Further, a higher probability to enroll in STEM MOOCs and smaller gender
      gaps in STEM MOOC enrollment and completion were found in less gender-equal and
      less economically developed countries.

PMID- 30212456
TI  - Detection of genetic alterations in gastric cancer patients from Saudi Arabia
      using comparative genomic hybridization (CGH).
AB  - BACKGROUND: The present study was conducted to discover genetic imbalances such
      as DNA copy number variations (CNVs) associated with gastric cancer (GC) and to
      examine their association with different genes involved in the process of gastric
      carcinogenesis in Saudi population. METHODS: Formalin-fixed paraffin-embedded
      (FFPE) tissues samples from 33 gastric cancer patients and 15 normal gastric
      samples were collected. Early and late stages GC samples were genotyped and CNVs
      were assessed by using Illumina HumanOmni1-Quad v.1.0 BeadChip. RESULTS: Copy
      number gains were more frequent than losses throughout all GC samples compared to
      normal tissue samples. The mean number of the altered chromosome per case was 64
      for gains and 40 for losses, and the median aberration length was 679115bp for
      gains and 375889bp for losses. We identified 7 high copy gain, 52 gains, 14
      losses, 32 homozygous losses, and 10 copy neutral LOHs (loss of
      heterozygosities). Copy number gains were frequently detected at 1p36.32, 1q12,
      1q22, 2p11.1, 4q23-q25, 5p12-p11, 6p21.33, 9q12-q21.11, 12q11-q12, 14q32.33,
      16p13.3, 17p13.1, 17q25.3, 19q13.32, and losses at 1p36.23, 1p36.32, 1p32.1,
      1q44, 3q25.2, 6p22.1, 6p21.33, 8p11.22, 10q22.1, 12p11.22, 14q32.12 and 16q24.2.
      We also identified 2 monosomy at chromosome 14 and 22, 52 partially trisomy and
      22 whole chromosome 4 neutral loss of heterozygosities at 13q14.2-q21.33, 5p15.2
      p15.1, 5q11.2-q13.2, 5q33.1-q34 and 3p14.2-q13.12. Furthermore, 11 gains and 2
      losses at 1p36.32 were detected for 11 different GC samples and this region has
      not been reported before in other populations. Statistical analysis confirms
      significant association of H. pylori infection with T4 stage of GC as compare to
      control and other stages. CONCLUSIONS: We found that high frequency of copy
      number gains and losses at 1p36.23, 1p32.1, 1p36.32, 3q25.2, 6p21.33 and 16q24.2
      may be common events in gastric cancer. While novel CNVs at 1p36.32 harbouring
      PRDM16, TP73 and TP73-AS1 genes showed 11 gains and 2 losses for 11 different GC
      cases and this region is not reported yet in Database of Genomic Variants may be
      specific to Saudi population.

PMID- 30212457
TI  - Exome sequencing-based identification of novel type 2 diabetes risk allele loci
      in the Qatari population.
AB  - BACKGROUND: Type 2 diabetes (T2D) susceptibility is influenced by genetic and
      lifestyle factors. To date, the majority of genetic studies of T2D have been in
      populations of European and Asian descent. The focus of this study is on genetic
      variations underlying T2D in Qataris, a population with one of the highest
      incidences of T2D worldwide. RESULTS: Illumina HiSeq exome sequencing was
      performed on 864 Qatari subjects (574 T2D cases, 290 controls). Sequence kernel
      association test (SKAT) gene-based analysis identified an association for low
      frequency potentially deleterious variants in 6 genes. However, these findings
      were not replicated by SKAT analysis in an independent cohort of 12,699 exomes,
      primarly due to the absence of low frequency potentially deleterious variants in
      5 of the 6 genes. Interestingly one of the genes identified, catenin beta 1
      (CTNNB1, beta-catenin), is the key effector of the Wnt pathway and interacts with
      the nuclear receptor transcription factor 7-like 2 (TCF7L2), variants which are
      the most strongly associated with risk of developing T2D worldwide. Single
      variant analysis did not identify any associated variants, suggesting the SKAT
      association signal was not driven by individual variants. None of the 6
      associated genes were among 634 previously described T2D genes. CONCLUSIONS: The
      observation that genes not previously linked to T2D in prior studies of European
      and Asian populations are associated with T2D in Qatar provides new insights into
      the complexity of T2D pathogenesis and emphasizes the importance of understudied
      populations when assessing genetic variation in the pathogenesis of common
      disorders.

PMID- 30212459
TI  - Innovative digital technologies for quality assurance of diagnosis of human
      African trypanosomiasis.

PMID- 30212460
TI  - Bacterial community composition in the salivary glands of triatomines (Hemiptera:
      Reduviidae).
AB  - BACKGROUND: Chagas disease is caused by the parasite Trypanosoma cruzi and is
      transmitted through triatomines (Hemiptera: Reduviidae). In the last year, many
      studies of triatomine gut microbiota have outlined its potential role in
      modulating vector competence. However, little is known about the microbiota
      present in the salivary glands of triatomines. Bacterial composition of salivary
      glands in selected triatomine species was investigated, as well as environmental
      influences on the acquisition of bacterial communities. METHODOLOGY/PRINCIPAL
      FINDINGS: The diversity of the bacterial communities of 30 pairs of salivary
      glands of triatomines was studied by sequencing of the V1- V3 variable region of
      the 16S rRNA using the MiSeq platform (Illumina), and bacteria isolated from skin
      of three vertebrate hosts were identified based on 16S rRNA gene sequence
      analysis (targeting the V3-V5 region). In a comparative analysis of microbiota in
      the salivary glands of triatomine species, operational taxonomic units belonging
      to Arsenophonous appeared as dominant in Triatoma spp (74% of the total 16S
      coverage), while these units belonging to unclassified Enterobacteriaceae were
      dominant in the Rhodnius spp (57% of the total 16S coverage). Some intraspecific
      changes in the composition of the triatomine microbiota were observed, suggesting
      that some bacteria may have been acquired from the environment. CONCLUSIONS AND
      SIGNIFICANCE: Our study revealed the presence of a low-diversity microbiota
      associated to the salivary glands of the evaluated triatomines. The predominant
      bacteria genera are associated with triatomine genera and the bacteria can be
      acquired in the environment in which the insects reside. Further studies are
      necessary to determine the influence of bacterial communities on vector
      competence.

PMID- 30212461
TI  - Modeling of xenobiotic transport and metabolism in virtual hepatic lobule models.
AB  - Computational models of normal liver function and xenobiotic induced liver damage
      are increasingly being used to interpret in vitro and in vivo data and as an
      approach to the de novo prediction of the liver's response to xenobiotics. The
      microdosimetry (dose at the level of individual cells) of xenobiotics vary
      spatially within the liver because of both compound-independent and compound
      dependent factors. In this paper, we build model liver lobules to investigate the
      interplay between vascular structure, blood flow and cellular transport that lead
      to regional variations in microdosimetry. We then compared simulation results
      obtained using this complex spatial model with a simpler linear pipe model of a
      sinusoid and a very simple single box model. We found that variations in
      diffusive transport, transporter-mediated transport and metabolism, coupled with
      complex liver sinusoid architecture and blood flow distribution, led to three
      essential patterns of xenobiotic exposure within the virtual liver lobule: (1)
      lobular-wise uniform, (2) radially varying and (3) both radially and azimuthally
      varying. We propose to use these essential patterns of exposure as a reference
      for selection of model representations when a computational study involves
      modeling detailed hepatic responses to xenobiotics.

PMID- 30212462
TI  - Thyromental height test as a new method for prediction of difficult intubation
      with double lumen tube.
AB  - BACKGROUND: Predicting difficult intubation is of high clinical interest.
      METHODS: 237 patients aged >=18 years were included in the study. Preoperative
      airway evaluation included: Mallampati test, thyromental distance, sternomental
      distance and thyromental height test. During direct laryngoscopy Cormack & Lehane
      classification was graded. We calculated the ROC AUC, sensitivity and specificity
      for thyromental height test as a primary end point of our study. RESULTS: Only
      thyromental height test and Cormack-Lehane scale proved significant on occurrence
      of difficult intubation. The optimal sensitivity and specificity values of
      thyromental height test were met with a cut off value of 50 mm. With 1 mm
      increase in thyromental height test, risk of difficult intubation decreased by
      7%. CONCLUSION: Thyromental height test is a simple, easy to perform and non
      invasive test to predict difficult intubation in patients scheduled for elective
      double lumen tube intubation during thoracic surgical procedures. With 1 mm above
      50 mm increase in thyromental height test the risk of difficult intubation
      decreased by 7%. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02988336.

PMID- 30212463
TI  - Flexibility and constraint: Evolutionary remodeling of the sporulation initiation
      pathway in Firmicutes.
AB  - The evolution of signal transduction pathways is constrained by the requirements
      of signal fidelity, yet flexibility is necessary to allow pathway remodeling in
      response to environmental challenges. A detailed understanding of how flexibility
      and constraint shape bacterial two component signaling systems is emerging, but
      how new signal transduction architectures arise remains unclear. Here, we
      investigate pathway remodeling using the Firmicute sporulation initiation (Spo0)
      pathway as a model. The present-day Spo0 pathways in Bacilli and Clostridia share
      common ancestry, but possess different architectures. In Clostridium
      acetobutylicum, sensor kinases directly phosphorylate Spo0A, the master regulator
      of sporulation. In Bacillus subtilis, Spo0A is activated via a four-protein
      phosphorelay. The current view favors an ancestral direct phosphorylation
      architecture, with the phosphorelay emerging in the Bacillar lineage. Our results
      reject this hypothesis. Our analysis of 84 broadly distributed Firmicute genomes
      predicts phosphorelays in numerous Clostridia, contrary to the expectation that
      the Spo0 phosphorelay is unique to Bacilli. Our experimental verification of a
      functional Spo0 phosphorelay encoded by Desulfotomaculum acetoxidans (Class
      Clostridia) further supports functional phosphorelays in Clostridia, which
      strongly suggests that the ancestral Spo0 pathway was a phosphorelay. Cross
      complementation assays between Bacillar and Clostridial phosphorelays demonstrate
      conservation of interaction specificity since their divergence over 2.7 BYA.
      Further, the distribution of direct phosphorylation Spo0 pathways is patchy,
      suggesting multiple, independent instances of remodeling from phosphorelay to
      direct phosphorylation. We provide evidence that these transitions are likely the
      result of changes in sporulation kinase specificity or acquisition of a sensor
      kinase with specificity for Spo0A, which is remarkably conserved in both
      architectures. We conclude that flexible encoding of interaction specificity, a
      phenotype that is only intermittently essential, and the recruitment of kinases
      to recognize novel environmental signals resulted in a consistent and repeated
      pattern of remodeling of the Spo0 pathway.

PMID- 30212464
TI  - First natural crossover recombination between two distinct species of the family
      Closteroviridae leads to the emergence of a new disease.
AB  - Lettuce chlorosis virus-SP (LCV-SP) (family Closteroviridae, genus Crinivirus),
      is a new strain of LCV which is able to infect green bean plants but not lettuce.
      In the present study, high-throughput and Sanger sequencing of RNA was used to
      obtain the LCV-SP full-length sequence. The LCV-SP genome comprises 8825 nt and
      8672 nt long RNA1 and RNA2 respectively. RNA1 of LCV-SP contains four ORFs, the
      proteins encoded by the ORF1a and ORF1b are closely related to LCV RNA1 from
      California (FJ380118) whereas the 3' end encodes proteins which share high amino
      acid sequence identity with RNA1 of Bean yellow disorder virus (BnYDV; EU191904).
      The genomic sequence of RNA2 consists of 8 ORFs, instead of 10 ORFs contained in
      LCV-California isolate. The distribution of vsiRNA (virus-derived small
      interfering RNA) along the LCV-SP genome suggested the presence of subgenomic
      RNAs corresponding with HSP70, P6.4 and P60. Results of the analysis using RDP4
      and Simplot programs are the proof of the evidence that LCV-SP is the first
      recombinant of the family Closteroviridae by crossover recombination of intact
      ORFs, being the LCV RNA1 (FJ380118) and BnYDV RNA1 (EU191904) the origin of the
      new LCV strain. Genetic diversity values of virus isolates in the recombinant
      region obtained after sampling LCV-SP infected green bean between 2011 and 2017
      might suggest that the recombinant virus event occurred in the area before this
      period. The presence of LCV-SP shows the role of recombination as a driving force
      of evolution within the genus Crinivirus, a globally distributed, emergent genus.

PMID- 30212465
TI  - Integrative proteomics and bioinformatic prediction enable a high-confidence
      apicoplast proteome in malaria parasites.
AB  - Malaria parasites (Plasmodium spp.) and related apicomplexan pathogens contain a
      nonphotosynthetic plastid called the apicoplast. Derived from an unusual
      secondary eukaryote-eukaryote endosymbiosis, the apicoplast is a fascinating
      organelle whose function and biogenesis rely on a complex amalgamation of
      bacterial and algal pathways. Because these pathways are distinct from the human
      host, the apicoplast is an excellent source of novel antimalarial targets.
      Despite its biomedical importance and evolutionary significance, the absence of a
      reliable apicoplast proteome has limited most studies to the handful of pathways
      identified by homology to bacteria or primary chloroplasts, precluding our
      ability to study the most novel apicoplast pathways. Here, we combine proximity
      biotinylation-based proteomics (BioID) and a new machine learning algorithm to
      generate a high-confidence apicoplast proteome consisting of 346 proteins.
      Critically, the high accuracy of this proteome significantly outperforms previous
      prediction-based methods and extends beyond other BioID studies of unique
      parasite compartments. Half of identified proteins have unknown function, and 77%
      are predicted to be important for normal blood-stage growth. We validate the
      apicoplast localization of a subset of novel proteins and show that an ATP
      binding cassette protein ABCF1 is essential for blood-stage survival and plays a
      previously unknown role in apicoplast biogenesis. These findings indicate
      critical organellar functions for newly discovered apicoplast proteins. The
      apicoplast proteome will be an important resource for elucidating unique pathways
      derived from secondary endosymbiosis and prioritizing antimalarial drug targets.

PMID- 30212466
TI  - Rural youths' understanding of gene x environmental contributors to heritable
      health conditions: The case of podoconiosis in Ethiopia.
AB  - OBJECTIVES: Assess the feasibility of engaging youth to disseminate accurate
      information about gene by environmental (GxE) influences on podoconiosis, a
      neglected tropical lymphedema endemic in southern Ethiopia. METHODS: A cross
      sectional survey was conducted with 377 youth randomly selected from 2 districts
      of Southern Ethiopia. Measures included GxE knowledge (4 true/false statements),
      preventive action knowledge (endorse wearing shoes and foot hygiene), causal
      misconceptions (11 items related to contagion) and confidence to explain GxE (9
      disagree/agree statements). RESULTS: Over half (59%) accurately endorsed joint
      contributions of gene and environment to podoconiosis and preventive mechanisms
      (e.g., wearing protective shoes and keeping foot hygiene). Multivariable logistic
      regression showed that youth with accurate understanding about GxE contributors
      reported having: some education, friends or kin who were affected by the
      condition, and prior interactions with health extension workers. Surprisingly,
      higher accurate GxE knowledge was positively associated with endorsing contagion
      as a causal factor. Accuracy of GxE and preventive action knowledge were
      positively associated with youth's confidence to explain podoconiosis-related
      information. CONCLUSIONS: Youth have the potential to be competent disseminators
      of GxE information about podoconiosis. Interventions to foster confidence among
      youth in social or kin relationships with affected individuals may be most
      promising. Efforts to challenge youth's co-existing inaccurate beliefs about
      contagion could strengthen the link of GxE explanations to preventive actions.

PMID- 30212467
TI  - Informational structures: A dynamical system approach for integrated information.
AB  - Integrated Information Theory (IIT) has become nowadays the most sensible general
      theory of consciousness. In addition to very important statements, it opens the
      door for an abstract (mathematical) formulation of the theory. Given a mechanism
      in a particular state, IIT identifies a conscious experience with a conceptual
      structure, an informational object which exists, is composed of identified parts,
      is informative, integrated and maximally irreducible. This paper introduces a
      space-time continuous version of the concept of integrated information. To this
      aim, a graph and a dynamical systems treatment is used to define, for a given
      mechanism in a state for which a dynamics is settled, an Informational Structure,
      which is associated to the global attractor at each time of the system. By
      definition, the informational structure determines all the past and future
      behavior of the system, possesses an informational nature and, moreover, enriches
      all the points of the phase space with cause-effect power by means of its
      associated Informational Field. A detailed description of its inner structure by
      invariants and connections between them allows to associate a transition
      probability matrix to each informational structure and to develop a measure for
      the level of integrated information of the system.

PMID- 30212468
TI  - Whole genome sequencing of Neisseria meningitidis W isolates from the Czech
      Republic recovered in 1984-2017.
AB  - INTRODUCTION: The study presents the analysis of whole genome sequence (WGS) data
      for Neisseria meningitidis serogroup W isolates recovered in the Czech Republic
      in 1984-2017 and their comparison with WGS data from other countries. MATERIAL
      AND METHODS: Thirty-one Czech N. meningitidis W isolates, 22 from invasive
      meningococcal disease (IMD) and nine from healthy carriers were analysed. The 33
      year study period was divided into three periods: 1984-1999, 2000-2009, and 2010
      2017. RESULTS: Most study isolates from IMD and healthy carriers were assigned to
      clonal complex cc22 (n = 10) in all study periods. The second leading clonal
      complex was cc865 (n = 8) presented by IMD (n = 7) and carriage (n = 1) isolates
      that emerged in the last study period, 2010-2017. The third clonal complex was
      cc11 (n = 4) including IMD isolates from the first (1984-1999) and third (2010
      2017) study periods. The following clonal complex was cc174 (n = 3) presented by
      IMD isolates from the first two study periods, i.e. 1984-1999 and 2000-2009. One
      isolate of each cc41/44 and cc1136 originated from healthy carriers from the
      second study period, 2000-2009. The comparison of WGS data for N. meningitidis W
      isolates recovered in the Czech Republic in the study period 1984-2017 and for
      isolates from other countries recovered in the same period showed that clonal
      complex cc865, ST-3342 is unique to the Czech Republic since 2010. Moreover, the
      comparison shows that cc11 in the Czech Republic does not comprise novel
      hypervirulent lineages reported from both European and non-European countries.
      All 31 study isolates were assigned to Bexsero(r) Antigen Sequence Types (BAST),
      and seven of them were of newly described BASTs. CONCLUSIONS: WGS analysis
      contributed considerably to a more detailed molecular characterization of N.
      meningitidis W isolates recovered in the Czech Republic over a 33-year period and
      allowed for a spatial and temporal comparison of these characteristics between
      isolates from the Czech Republic and other countries. The most interesting
      finding of this study is that eight of 31 Czech isolates of N. meningitidis W
      belong to clonal complex cc865, which is uncommon for serogroup W. In addition,
      the WGS data precised the base for the update of the recommendation for
      vaccination in the Czech Republic.

PMID- 30212469
TI  - Microvillous cells in the olfactory epithelium express elements of the solitary
      chemosensory cell transduction signaling cascade.
AB  - The nasal cavity hosts an array of chemoresponsive cells, including the extended
      olfactory system and several other cells involved in detection of and responses
      to irritants. Solitary chemosensory cells (SCCs), which respond to irritants and
      bacteria, express the transient receptor potential channel TRPM5 an essential
      element of the taste transduction-signaling cascade. Microvillous cells (MVCs),
      non-neuronal cells situated in the apical layer of the main olfactory epithelium,
      also express TRPM5, but their function has not yet been clarified. TRPM5-positive
      MVCs, like SCCs, show a cholinergic phenotype expressing choline acetyl
      transferase (ChAT), but none of the other elements of the bitter taste
      transduction cascade could be detected. We reexamined TRPM5-positive MVCs with
      more sensitive gene expression and staining techniques to clarify whether they
      rely only on TRPM5 and ChAT or express other elements of the taste/SCC
      transduction cascade. Analyzing existing RNA sequencing data from whole olfactory
      mucosa and isolated olfactory sensory neurons, we determined that several
      elements of the taste/SCC transduction cascade, including taste receptors, are
      expressed in the olfactory mucosa in cells other than olfactory sensory neurons.
      Immunostaining confirmed the presence TRPM5 and ChAT in a subset of cells of the
      olfactory mucosa, which also showed the expression of PLCB2, gustducin, and T1R3.
      Specifically, these cells were identified as TRPM5-positive MVCs. Furthermore, we
      examined whether MVCs are innervated by trigeminal fibers, similarly to SCCs.
      Using antibodies against trigeminal nerve markers calcitonin gene-related peptide
      and substance P, we determined that, despite the cholinergic phenotype, most MVCs
      in the olfactory mucosa lacked consistent trigeminal innervation. Our findings
      indicate that MVCs, like SCCs, express all the elements of the bitter taste
      transduction cascade but that, unlike SCCs, they possess only sparse trigeminal
      innervation. The cholinergic phenotype of MVCs suggests a modulatory function of
      the surrounding olfactory epithelium, through the release of acetylcholine.

PMID- 30212470
TI  - Ginsenoside Rb1 does not halt osteoporotic bone loss in ovariectomized rats.
AB  - Osteoporosis (OP) is a systemic skeletal disorder, manifesting with a reduction
      in bone mass and deterioration of the microarchitecture. Mesenchymal stem cells
      (MSCs) have an innate ability to differentiate into several cell types, including
      osteoblasts (OB). Ginsenoside Rb1 (GRb1) is an ethanol extract from ginseng and
      contains a highly concentrated form of ginsenoside. GRb1 shows extensive
      beneficial health effects such as anti-oxidative and anti-inflammatory functions,
      modulating the immune system and inhibiting osteoclastogenesis. We hypothesized
      that GRb1 can promote MSC differentiation into OBs and inhibit bone loss. In the
      present study, we aimed to address two questions: (1) Will GRb1 have a positive
      effect on osteogenic differentiation of MSCs? and (2) Will GRb1 halt bone loss in
      ovariectomized (OVX) rats? We investigated the effects of GRb1 on viability and
      osteogenic differentiation of rat mesenchymal stem cells (rMSCs). Our results
      showed that GRb1 at concentrations of 10-8 M and 10-6 M can increase alkaline
      phosphatase activity, mineralization and the expression of osteogenic related
      proteins, such as osteopontin and osteoprotegerin, while incubating rMSCs with
      osteogenic induction medium and GRb1. Adding GRb1 into the medium can prevent
      rMSCs from Oxidative damage at the concentration of 25MUM H2O2. Furthermore, 40 4
      month-old rats were assigned to 5 groups(8 rats per group): the basal group, the
      sham group, the OVX group, the high dose of GRb1 group (6 mg/kg/day) and the low
      dose of GRb1 group (3 mg/kg/day). Rats recrived treatment 3days after surgery and
      last for 14 weeks. Examinations included serum analysis, mechanical testing,
      Masson-Goldner trichrome staining and bone histomorphometry analysis. The results
      showed that OVX can lead to dyslipidemia and excessive oxidative stress, whereas
      GRb1 cannot significantly halt dyslipidemia and excessive oxidative stress in OVX
      rats. In addition, the bone density of the lumbar vertebra and femur were
      decreased significantly in the OVX rats, and GRb1 could not inhibit bone loss.
      Bone histomorphometry analysis showed that the number and width of bone trabecula
      of the tibia were reduced in OVX rats, and GRb1 could not prevent their
      occurrence. A bone biomechanics assay showed that GRb1 cannot improve the ability
      of bone structure to resist fracture of the femur in OVX rats. The current study
      demonstrated that GRb1 has an obvious effect on osteogenic differentiation in
      rMSCs but no obvious effect on bone loss in OVX rats. These findings indicate
      GRb1 has a positive effect on rMSCs but does not have an effect on bone loss in
      OVX rats at the concentration we used.

PMID- 30212471
TI  - Bayesian analysis of isothermal titration calorimetry for binding thermodynamics.
AB  - Isothermal titration calorimetry (ITC) is the only technique able to determine
      both the enthalpy and entropy of noncovalent association in a single experiment.
      The standard data analysis method based on nonlinear regression, however,
      provides unrealistically small uncertainty estimates due to its neglect of
      dominant sources of error. Here, we present a Bayesian framework for sampling
      from the posterior distribution of all thermodynamic parameters and other
      quantities of interest from one or more ITC experiments, allowing uncertainties
      and correlations to be quantitatively assessed. For a series of ITC measurements
      on metal:chelator and protein:ligand systems, the Bayesian approach yields
      uncertainties which represent the variability from experiment to experiment more
      accurately than the standard data analysis. In some datasets, the median enthalpy
      of binding is shifted by as much as 1.5 kcal/mol. A Python implementation
      suitable for analysis of data generated by MicroCal instruments (and adaptable to
      other calorimeters) is freely available online.

PMID- 30212473
TI  - Traceable ciphertext-policy attribute-based encryption scheme with attribute
      level user revocation for cloud storage.
AB  - In a ciphertext-policy attribute-based encryption (CP-ABE) scheme, a user may
      have multiple attributes, and each attribute may be shared simultaneously by many
      users. The decryption key of an attribute can thus be shared by many users who
      all possess the attribute. For monetary gain, a malicious authorized user may
      reveal his/her decryption key to a third party, and it is difficult to trace the
      owner of primitive secret key from an exposed key. At the same time, this
      situation may also limit commercial applications of CP-ABE systems. To solve
      these problems and enable fine-grained access control for the encrypted data, we
      propose a traceable CP-ABE scheme with attribute-level user revocation for cloud
      storage (TUR-CPABE). Our scheme enjoys four advantages. First, it has the ability
      to trace malicious users who have leaked key information from the system. Second,
      it supports attribute-level user revocation for malicious users and allows ABE
      fine-grained access control. Third, it allows secret key updates and ciphertext
      updates to resist collusion attacks between users. Fourth, outsourcing
      encryption, decryption and attribute revocation are used to reduce the
      computational burden on data owners, data users and the trust authority,
      respectively. In addition, our scheme has been proven to be secure against chosen
      plaintext attacks under a selective access policy based on decisional q - BDHE
      assumption in the standard model.

PMID- 30212472
TI  - The impact of surveillance and control on highly pathogenic avian influenza
      outbreaks in poultry in Dhaka division, Bangladesh.
AB  - In Bangladesh, the poultry industry is an economically and socially important
      sector, but it is persistently threatened by the effects of H5N1 highly
      pathogenic avian influenza. Thus, identifying the optimal control policy in
      response to an emerging disease outbreak is a key challenge for policy-makers. To
      inform this aim, a common approach is to carry out simulation studies comparing
      plausible strategies, while accounting for known capacity restrictions. In this
      study we perform simulations of a previously developed H5N1 influenza
      transmission model framework, fitted to two separate historical outbreaks, to
      assess specific control objectives related to the burden or duration of H5N1
      outbreaks among poultry farms in the Dhaka division of Bangladesh. In particular,
      we explore the optimal implementation of ring culling, ring vaccination and
      active surveillance measures when presuming disease transmission predominately
      occurs from premises-to-premises, versus a setting requiring the inclusion of
      external factors. Additionally, we determine the sensitivity of the management
      actions under consideration to differing levels of capacity constraints and
      outbreaks with disparate transmission dynamics. While we find that reactive
      culling and vaccination policies should pay close attention to these factors to
      ensure intervention targeting is optimised, across multiple settings the top
      performing control action amongst those under consideration were targeted
      proactive surveillance schemes. Our findings may advise the type of control
      measure, plus its intensity, that could potentially be applied in the event of a
      developing outbreak of H5N1 amongst originally H5N1 virus-free commercially
      reared poultry in the Dhaka division of Bangladesh.

PMID- 30212474
TI  - Potential carbon storage in biochar made from logging residue: Basic principles
      and Southern Oregon case studies.
AB  - The industrial production of long-lived charcoal products (commonly referred to
      as biochar) from otherwise shorter-lived logging resides (commonly referred to a
      slash) has been proposed as a means to increasing terrestrial carbon storage thus
      mitigating global warming caused by anthropogenic greenhouse gas emissions. We
      present a generalized model that describes the temporal dynamics of biochar
      carbon stocks, relative to carbon of unmodified logging residue, and evaluate the
      sensitivity of carbon storage to various biophysical and production parameters.
      Using this model, we then attribute net carbon storage to several potential
      biochar production scenarios, specifically engineered to use wood recovered from
      harvests prescribed to reduce fire hazard in mixed-conifer forests of South
      central Oregon. Relative to a baseline scenario where logging residue is left to
      decay on site, the net carbon storage attributed to 20 years of biochar
      production is generally negative for the first several decades, then remains
      positive for several centuries at levels approximately one-fourth the total
      feedstock carbon processed. Positive net carbon storage and the time required for
      it to manifest is notably sensitive to biochar conversion efficiencies, logging
      residue decay rates, and alternate baseline fates of logging residue. The
      magnitude of net carbon storage, and the time required for it to become positive,
      is largely similar across range of production facility types. Moreover, the time
      required for net carbon storage to become positive, and its magnitude over the
      first 100 years is notably insensitive to biochar decomposition rates provided
      biochar decays at least ten-times slower than the logging residue it is made
      from.

PMID- 30212475
TI  - Trend analysis of major cancer statistics according to sex and severity levels in
      Korea.
AB  - Existing epidemiologic reports or studies of cancer statistics in Korea lack
      sufficient data on cancer severity distributions and observed survival rates.
      This study analyzed trends in major cancer statistics according to sex and
      severity levels in Korea from 2006 to 2013. We included eight cancers
      (hepatocellular carcinoma, and thyroid, colorectal, gastric, lung, prostate,
      breast, and cervical cancer), using Korea Central Cancer Registry data. Severity
      level was classified by Surveillance, Epidemiology, and End Results (SEER) stage
      as follows: localized, regional, distant, or unknown. Numbers of incident cancer
      cases from 2006 to 2013 were described by sex and SEER stage. We estimated up to
      8-year observed survival rates of major cancers by sex and SEER stage, and
      provided prevalence rates by sex and SEER stage in 2011, 2012, and 2013. Although
      increases in new cancer cases are slowing and the total number of incident cancer
      cases in 2013 decreased for the first time since 2006, the number of prevalent
      cancer cases was 663,530 in 2013, an increase of 13.3% compared to 2011. Among
      the five cancers affecting both sexes, sex-related differences in 5-year observed
      survival rates for lung cancer were greatest in the localized stage (men, 31.9%;
      women, 48.1%), regional stage (men, 20.0%; women, 31.3%), and unknown stage (men,
      24.3%; women, 37.5%). The sum of the proportions of localized and regional stages
      for thyroid and breast cancer was over 90% in 2013, while the sum of the
      proportions of localized and regional stages for lung cancer was only 56.7% in
      2013. Differences in observed survival rates between men and women were prominent
      in lung cancer for all SEER stages. The reported epidemiologic data from this
      study can be used to obtain a more valid measure of cancer burden using a summary
      measure of population health.

PMID- 30212476
TI  - Longitudinal study of multiple sclerosis lesions using ultra-high field (7T)
      multiparametric MR imaging.
AB  - Pathophysiology of multiple sclerosis (MS) lesions is dynamic and changes over
      time. The purpose of this exploratory study was to determine the longitudinal
      changes in MS lesions over time on ultra-high field MR imaging. Nine patients
      with MS underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D
      gradient-echo-T2*-weighted imaging on 7T MRI at baseline and after ~2.4 years of
      follow-up. Morphologic imaging characteristics, signal intensity patterns and
      quantitative susceptibility mapping (QSM) values of lesions were recorded at both
      time points. Lesions were classified as "iron-laden" if they demonstrated
      hypointense signal on T2*-weighted images and/or SWI as well as hyperintense
      signal on QSM. Lesions were considered "non-iron-laden" if they were hyperintense
      on T2*/SWI and isointense or hyperintense on QSM. Total of 162 non-iron-laden and
      29 iron-laden lesions were observed at baseline. No change in baseline lesion
      size during follow up was recorded in 92.7%; no change in lesion-vessel
      relationship in 86.5%; and no change in signal intensity pattern in 96.9% of
      lesions. Three lesions which were non-iron-laden at baseline, exhibited iron at
      follow-up. In two iron-laden lesions, redistribution of iron content was observed
      at follow-up. Two-thirds of these iron-laden lesions showed an increase in QSM at
      follow-up relative to baseline, and the remaining one-third exhibited decrease in
      QSM. Most of the newly formed lesions (11/13, 84.6%) at follow-up were iron
      laden. 7T multiparametric MRI is a useful tool for tracking the evolution of MS
      lesions, especially with regard to changes in iron content.

PMID- 30212477
TI  - Antibiotic usage in surgical prophylaxis: A prospective observational study in
      the surgical ward of Nekemte referral hospital.
AB  - BACKGROUND: Surgical antimicrobial prophylaxis guidelines are considered as
      important interventional tools for antimicrobial resistance. Guideline compliance
      was poor across different countries and thus results in an inappropriate and
      overuse of antibiotics. OBJECTIVE: To evaluate the selection, timing and duration
      of prophylactic antibiotic administration among surgical patients in Nekmte
      referral hospital. METHOD: Prospective, facility based cross-sectional study was
      conducted from 1st April to 30th June 2017. Data were collected using data
      abstraction format among surgical inpatients prescribed with surgical antibiotic
      prophylaxis. Surgical antimicrobial prophylaxis guidelines were used as data
      assessment protocols. SPSS version 21.0 was used for data entry and analysis.
      Descriptive statistics and binary logistic regression were used for analysis.
      RESULTS: The median age of the study participants was 35.0 (IQR: 25-50) years
      with the preponderance (58.8%) of male patients. The median hospitalization
      period was 8.0 (IQR: 5-11) days. Majority of the participants were from the
      general surgical ward (60.1%). About 43% of the procedures were clean. Most of
      the surgical cases were gastrointestinal (39.2%). Only 10.6% of the drug
      selections comply with American Society of Health-System Pharmacists guideline.
      Surprisingly, none of the selections were compliant to the national Standard
      Treatment Guideline of the country. About 84% of the study participants received
      ceftriaxone. Majority of the prophylactic antibiotics (75.8%) were administered
      for greater than 24 hours and above half (52.3%) of the antibiotics were
      administered preoperatively. Emergent surgery procedures (AOR = 2.89, 95% CI:
      (1.09-9.10) and being a male patient (AOR = 3.10, 95% CI: 1.07-8.98) were
      associated with inappropriate preoperative antibiotic administration. Patients
      admitted to the gynecology and obstetrics ward was less likely to receive
      surgical prophylaxis for greater than 24 hours (AOR = 0.07, 95% CI: 0.01-0.81).
      CONCLUSION: Surgical antibiotic compliance was far below the guideline
      recommendation. Patients admitted in the gynecology and obstetrics ward were more
      likely to comply with the surgical antimicrobial prophylaxis duration
      recommendation. The timing was most likely to be inappropriate among male
      patients and patients on emergent surgery. Availability and awareness creation on
      the antibiotic drugs and the guidelines were important interventions recommended
      for appropriate surgical antimicrobial use.

PMID- 30212479
TI  - Anti-cancer effects of disulfiram in head and neck squamous cell carcinoma via
      autophagic cell death.
AB  - BACKGROUND: Disulfiram (DSF), which is used to treat alcohol dependence, has been
      reported to have anti-cancer effects in various malignant tumors. In this study,
      we investigated the anti-cancer effects and mechanism of DSF in HNSCC. METHODS:
      Head and neck squamous carcinoma cell lines (FaDu and Hep2) were used to analyze
      the anti-cancer effects of DSF. The anti-cancer effects of DSF were confirmed in
      vivo using a xenograft tumor model. RESULTS: The anti-cancer effects of DSF in
      HNSCC were found to be copper (Cu) dependent. Specifically, DSF/Cu markedly
      inhibited HNSCC at a concentration of 1 MUM. After DSF/Cu administration,
      production of reactive oxygen species (ROS) was remarkable starting at 0.5 MUM,
      suggesting that the inhibitory effects of DSF/Cu on HNSCC are mediated through
      the formation of ROS. The levels of phospho-JNK, phospho-cJun and phospho-p38
      were increased after DSF/Cu treatment while levels of phospho-Akt were decreased.
      These results suggested that the inhibitory effects of DSF/Cu on HNSCC cells
      involve ROS formation and down-regulation of Akt-signaling. Through these
      molecular mechanisms, DSF ultimately induce the inhibitory effects on HNSCC cell
      lines mainly through autophagic cell death, not apoptotic cell death. Lastly, we
      investigated the clinical relevance of DSF/Cu using a HNSCC xenograft animal
      model, which showed that tumor growth was remarkably decreased by DSF (50 mg/kg
      injection). CONCLUSION: In treating patients with HNSCC, DSF may contribute to
      improved HNSCC patient's survival. The characteristic anti-cancer effects of DSF
      on HNSCC may suggest new therapeutic potential for this medication in HNSCC
      patients.

PMID- 30212478
TI  - HbA1c, lipid profiles and risk of incident type 2 Diabetes in United States
      Veterans.
AB  - United States Veterans are at excess risk for type 2 diabetes, but population
      differentials in risk have not been characterized. We determined risk of type 2
      diabetes in relation to prediabetes and dyslipidemic profiles in Veterans at the
      VA New York Harbor (VA NYHHS) during 2004-2014. Prediabetes was based on American
      Diabetes Association hemoglobin A1c (HbA1c) testing cut-points, one of several
      possible criteria used to define prediabetes. We evaluated transition to type 2
      diabetes in 4,297 normoglycemic Veterans and 7,060 Veterans with prediabetes. Cox
      proportional hazards regression was used to relate HbA1c levels, lipid profiles,
      demographic, anthropometric and comorbid cardiovascular factors to incident
      diabetes (Hazard Ratio [HR] and 95% confidence intervals). Compared to
      normoglycemic Veterans (HbA1c: 5.0-5.6%; 31-38 mmol/mol), risks for diabetes were
      >2-fold in the moderate prediabetes risk group (HbA1c: 5.7-5.9%; 39-41 mmol/mol)
      (HR 2.37 [1.98-2.85]) and >5-fold in the high risk prediabetes group (HbA1c: 6.0
      6.4%; 42-46 mmol/mol) (HR 5.59 [4.75-6.58]). Risks for diabetes were increased
      with elevated VLDL (>=40mg/dl; HR 1.31 [1.09-1.58]) and TG/HDL (>=1.5mg/dl; HR
      1.34 [1.12-1.59]), and decreased with elevated HDL (>=35mg/dl; HR 0.80 [0.67
      0.96]). Transition to diabetes in Veterans was related in age-stratified risk
      score analyses to HbA1c, VLDL, HDL and TG/HDL, BMI, hypertension and race, with 5
      year risk differentials of 62% for the lowest (5-year risk, 13.5%) vs. the
      highest quartile (5-year risk, 21.9%) of the risk score. This investigation
      identified substantial differentials in risk of diabetes in Veterans, based on a
      readily-derived risk score suitable for risk stratification for type 2 diabetes
      prevention.

PMID- 30212480
TI  - Measurement invariance of the SF-12 among different demographic groups: The
      HELIUS study.
AB  - AIM: To investigate whether items of the SF-12, widely used to assess health
      outcome in clinical practice and public health research, provide unbiased
      measurements of underlying constructs in different demographic groups regarding
      gender, age, educational level and ethnicity. METHODS: We included 23,146 men and
      women aged 18-70 of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian,
      Turkish, or Moroccan origin from the HELIUS study. Both multiple group
      confirmatory factor analyses (MGCFA), with increasingly stringent model
      constraints (i.e. assessing Configural, Metric, Strong and Strict measurement
      invariance (MI)), and regression analysis were conducted to establish
      comparability of SF-12 items across demographic groups. RESULTS: MI regarding
      gender, age and education was tested in the ethnic Dutch group (N = 4,615). In
      each subsequent step of testing MI, change in goodness-of-fit measures did not
      exceed 0.010 (RMSEA) or 0.004 (CFI). Moreover, goodness-of-fit indices showed
      good fit for strict invariance models: RMSEA<0.055; CFI>0.97. Regarding
      ethnicity, RMSEA values of metric and subsequent models fell above 0.055,
      indicating violation of measurement invariance in factor loadings, thresholds and
      residual variances. Regression analysis revealed possible age-, education- and
      ethnicity-related DIF. Adjustment for this DIF had little impact on the magnitude
      of age and educational differences in physical and mental health, but ethnic
      inequalities in physical health-and to a lesser extent mental health-were reduced
      after DIF adjustment. CONCLUSIONS: We found no evidence of violation of
      measurement invariance of the SF-12 regarding gender, age and educational level.
      If minor DIF would remain undetected in our MGCFA analyses, we showed that this
      would have negligible effect on the magnitude of demographic health inequalities.
      Regarding ethnicity, the SF-12 was not measurement invariant. After accounting
      for DIF, we observed a reduction of ethnic inequalities in health, in particular
      in physical health. Caution is warranted when comparing SF-12 scores across
      population groups with various ethnic backgrounds.

PMID- 30212481
TI  - Red cell distribution width and common disease onsets in 240,477 healthy
      volunteers followed for up to 9 years.
AB  - Higher Red Blood Cell Distribution Width (RDW or anisocytosis) predicts incident
      coronary artery disease (CAD) plus all-cause and cardiovascular mortality, but
      its predictive value for other common diseases in healthy volunteers is less
      clear. We aimed to determine the shorter and longer term associations between RDW
      and incident common conditions in participants free of baseline disease, followed
      for 9 years. We undertook a prospective analysis of RDW% using 240,477 healthy UK
      Biobank study volunteers aged 40-70 years at baseline, with outcomes ascertained
      during follow-up (<=9 years). Participants were free of anemia, CAD, type-2
      diabetes, stroke, hypertension, COPD, and any cancer (except non-melanoma skin
      cancer) at baseline. Survival models (with competing Hazards) tested associations
      with outcomes from hospital admission records and death certificates. High RDW
      (>=15% variation, n = 6,050) compared to low (<12.5% n = 20,844) was strongly
      associated with mortality (HR 3.10: 95% CI 2.57 to 3.74), adjusted for age, sex,
      smoking status, education level, mean cell volume and hemoglobin concentration.
      Higher RDW was also associated with incident CAD (sub-HR 1.67: 1.40 to 1.99),
      heart failure, peripheral vascular disease, atrial fibrillation, stroke, and
      cancer (sHR 1.37: 1.21 to 1.55; colorectal cancer sHR 1.92: 1.36 to 2.72),
      especially leukemia (sHR 2.85: 1.63 to 4.97). Associations showed dose-response
      relationships, and RDW had long-term predictive value (>=4.5 years after
      assessment) for the majority of outcomes, which were similar in younger and older
      persons. In conclusion, higher RDW predicted onsets of a wide range of common
      conditions as well as mortality in a large healthy volunteer cohort. RDW is not
      just a short term predictor, as high levels were predictive 4.5 to 9 years after
      baseline in healthy volunteers. The wide range of outcomes reflects known RDW
      genetic influences, including diverse disease risks. RDW may be a useful clinical
      marker for inclusion in wellness assessments.

PMID- 30212482
TI  - PPARalpha-mediated peroxisome induction compensates PPARgamma-deficiency in
      bronchiolar club cells.
AB  - Despite the important functions of PPARgamma in various cell types of the lung,
      PPARgamma-deficiency in club cells induces only mild emphysema. Peroxisomes are
      distributed in a similar way as PPARgamma in the lung and are mainly enriched in
      club and AECII cells. To date, the effects of PPARgamma-deficiency on the overall
      peroxisomal compartment and its metabolic alterations in pulmonary club cells are
      unknown. Therefore, we characterized wild-type and club cell-specific PPARgamma
      knockout-mice lungs and used C22 cells to investigate the peroxisomal compartment
      and its metabolic roles in the distal airway epithelium by means of 1) double
      immunofluorescence labelling for peroxisomal proteins, 2) laser-assisted
      microdissection of the bronchiolar epithelium and subsequent qRT-PCR, 3) siRNA
      transfection of PPARgammaand PPRE dual-luciferase reporter activity in C22 cells,
      4) PPARg inhibition by GW9662, 5) GC-MS based lipid analysis. Our results reveal
      elevated levels of fatty acids, increased expression of PPARalpha and PPRE
      activity, a strong overall upregulation of the peroxisomal compartment and its
      associated gene expression (biogenesis, alpha-oxidation, beta-oxidation, and
      plasmalogens) in PPARgamma-deficient club cells. Interestingly, catalase was
      significantly increased and mistargeted into the cytoplasm, suggestive for
      oxidative stress by the PPARgamma-deficiency in club cells. Taken together,
      PPARalpha-mediated metabolic induction and proliferation of peroxisomes via a
      PPRE-dependent mechanism could compensate PPARgamma-deficiency in club cells.

PMID- 30212483
TI  - Prevalence and spectrum of AKT1, PIK3CA, PTEN and TP53 somatic mutations in
      Chinese breast cancer patients.
AB  - Breast cancer, one of the most frequently occurring cancers worldwide, is the
      leading cause of cancer-related death among women. AKT1, PIK3CA, PTEN and TP53
      mutations were common observed in breast cancer representing potential clinical
      biomarkers for cancer classification and treatment. A comprehensive knowledge of
      AKT1, PIK3CA, PTEN and TP53 mutations in breast cancer was still insufficient in
      Chinese population. In this study, the complete coding regions and exon-intron
      boundaries of AKT1, PIK3CA, PTEN and TP53 genes were sequenced in paired breast
      tumor and normal tissues from 313 Chinese breast cancer patients using
      microfluidic PCR-based target enrichment and next-generation sequencing
      technology. Total 120 somatic mutations were identified in 190 of the 313
      patients (60.7%), with the mutation frequency of AKT1 as 3.2%, PIK3CA as 36.4%,
      PTEN as 4.8%, and TP53 as 33.9%. Among these mutations, 1 in PIK3CA (p.I69N), 3
      in PTEN (p.K62X, c.635-12_636delTTAACCATGCAGAT and p.N340IfsTer4) and 5 in TP53
      (p.Q136AfsTer5, p.K139_P142del, p.Y234dup, p.V274LfsTer31 and p.N310TfsTer35)
      were novel. Notably, PIK3CA somatic mutations were significantly associated with
      ER-positive or PR-positive tumors. TP53 somatic mutations were significantly
      associated with ER-negative, PR-negative, HER2-positive, BRCA1 mutation, Ki67
      high expression and basal-like tumors. Our findings provided a comprehensive
      mutation profiling of AKT1, PIK3CA, PTEN and TP53 genes in Chinese breast cancer
      patients, which have potential implications in clinical management.

PMID- 30212484
TI  - Alexithymia mediates the relationship between interoceptive sensibility and
      anxiety.
AB  - A number of empirical and theoretical reports link altered interoceptive
      processing to anxiety. However, the mechanistic understanding of the relationship
      between the two remains poor. We propose that a heightened sensibility for
      interoceptive signals, combined with a difficulty in attributing these sensations
      to emotions, increases an individual's vulnerability to anxiety. In order to
      investigate this, a large sample of general population adults were recruited and
      completed self-report measures of interoceptive sensibility, trait anxiety and
      alexithymia. Results confirmed that the positive association between
      interoceptive sensibility and trait anxiety was partially mediated by
      alexithymia, such that those most at risk for clinically significant levels of
      trait anxiety have both significantly higher levels of interoceptive sensibility
      and alexithymia. A subsequent factor analysis confirmed the independence of the
      three measures. Altered interoceptive processing in combination with alexithymia,
      increased the risk for anxiety above and beyond altered interoceptive processing
      alone. We suggest that a heightened sensibility for interoceptive signals,
      combined with a difficulty in attributing these sensations to emotions, leaves
      these sensations vulnerable to catastrophizing interpretation. Interventions that
      target the attribution of bodily sensations may prove valuable in reducing
      anxiety.

PMID- 30212485
TI  - Readmissions of adults within three age groups following hospitalization for
      pneumonia: Analysis from the Nationwide Readmissions Database.
AB  - BACKGROUND: While 30-day readmissions following hospitalization for pneumonia
      have been well-studied in the elderly, their burden in young adults remains
      poorly understood. OBJECTIVE: To study patterns of readmissions following
      hospitalization for pneumonia across age groups and insurance payers. METHODS: In
      the Nationwide Readmission Database for the years 2013 and 2014 we identified all
      adults (>=18 years) discharged alive after a hospitalization with the primary
      diagnosis of pneumonia, and examined rates of readmissions within 30-days of
      discharge. Using covariates included in the Center for Medicare & Medicaid
      Services risk-adjustment model for pneumonia readmissions in a multivariable
      regression model for survey data, we identified predictors of 30-day readmission.
      RESULTS: We identified 629,939 index pneumonia hospitalizations with a weighted
      estimate of 1,472,069 nationally. Overall, 16.2% of patients were readmitted
      within 30 days of their hospitalization for pneumonia, with 30-day readmission
      rates of 12.4% in the 18-44 year age-group, 16.1% in the 45-64 year age-group,
      and 16.7% in the >=65-year age-group. In risk-adjusted analyses, compared with
      elderly, middle-aged adults were more likely to be readmitted (risk-adjusted OR
      1.05, 95% CI 1.03-1.07). Mean cost per readmission was also highest for this age
      group at $15,976. CONCLUSION: Middle-aged adults experience substantial rates of
      30-day readmission that are comparable to those over 65 years of age, with a
      higher cost per readmission event. Future efforts are needed to identify
      potential interventions to alleviate the high burden of pneumonia readmissions in
      middle-aged adults.

PMID- 30212486
TI  - A comprehension scale for central-line associated bloodstream infection: Results
      of a preliminary survey and factor analysis.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSI) are
      associated with significant morbidity and mortality. This condition is therefore
      the focus of quality initiatives, which primarily use audit and feedback to
      improve performance. However, feedback of quality data inconsistently affects
      clinician behavior. A hypothesis for this inconsistency is that a lack of
      comprehension of CLABSI data by decision makers prevents behavior change. In
      order to rigorously test this hypothesis, a comprehension scale is necessary.
      Therefore, we sought to develop a scale to assess comprehension of CLABSI quality
      metric data. METHODS: The initial instrument was constructed via an exploratory
      approach, including literature review and iterative item development. The
      developed instrument was administered to a sample of clinicians, and each item
      was scored dichotomously as correct or incorrect. Psychometric evaluation via
      exploratory factor analyses (using tetrachoric correlations) and Cronbach's alpha
      were used to assess dimensionality and internal consistency. RESULTS: 97
      clinicians responded and were included. Factor analyses yielded a scale with one
      factor containing four items with an eigenvalue of 2.55 and a Cronbach's alpha of
      0.82. The final solution was interpreted as an overall CLABSI "comprehension"
      scale given its unidimensionality and assessment of each piece of data within the
      CLABSI feedback report. The cohort had a mean performance on the scale of 49%
      correct (median = 50%). CONCLUSIONS: We present the first psychometric evaluation
      of a preliminary scale that assesses clinician comprehension of CLABSI quality
      metric data. This scale has internal consistency, assesses clinically relevant
      concepts related to CLABSI comprehension, and is brief, which will assist in
      response rates. This scale has potential policy relevance as it could aid efforts
      to make quality metrics more effective in driving practice change.

PMID- 30212487
TI  - Quality appraisal of clinical guidelines for surgical site infection prevention:
      A systematic review.
AB  - BACKGROUND: Surgical site infections (SSI) occur in up to 10% of surgeries. Wound
      care practices to prevent infections are guided by Clinical Practice Guidelines
      (CPGs), yet their contribution to improving patient outcomes relies on their
      quality and adoption in practice. We critically evaluated the quality of CPGs for
      SSI prevention during pre-, intra- and post-operative phases of care. METHODS: We
      systematically reviewed the literature from 1990-2018 using the Cochrane Library,
      CINAHL, EMBASE, MEDLINE, ProQuest databases and five guidelines repositories. We
      extracted characteristics of each guideline using purposely-developed data
      collection tools. We assessed overall quality using the Appraisal of Guidelines
      for Research and Evaluation II (AGREE II) tool. RESULTS: Combined searches of
      databases and repositories yielded 5,910 citations. Of these, we reviewed 215
      full text documents. The final sample included 15 documents: 6 complete CPGs, 3
      CPG updates, and 6 supplementary documents. The overall %mean scores across AGREE
      II domains for CPGs were: 1) scope and purpose (%mean +/- SD = 86.3+/-23.5); 2)
      stakeholder involvement (%mean +/- SD = 64+/-31.0); 3) rigour of development
      (%mean +/- SD = 68.7+/-30.6); 4) clarity and presentation (%mean +/- SD = 88.5+/
      16.7); 5) applicability (%mean +/- SD = 44+/-30.2); and, 5) editorial
      independence (%mean +/- SD = 61+/-37.6). Based on individual AGREE II domains and
      overall scores, we appraised 4 out of 6 CPGs (inclusive of updates) as
      "recommended" for use in practice. Overall agreement among appraisers was
      excellent (ICC 0.86 [95%CI 0.73-0.94] - 0.98 [95%CI 0.96-0.99]; p <0.001).
      DISCUSSION: International interest in CPG development has resulted in refinements
      to methodologies, which has led to improvements in the overall quality of the
      product. IMPLICATIONS FOR TRANSLATION: Given the domains that received the lowest
      scores, it is clear that we need more consumer involvement and better
      consideration of the implementation challenges with CPG uptake and
      sustainability.

PMID- 30212488
TI  - Comparison of Esterman disability scores obtained using Goldmann perimetry and
      the Humphrey field analyzer in Japanese low-vision patients.
AB  - PURPOSE: To compare the Esterman Disability Score (EDS) obtained with Goldmann
      perimetry (GP) testing and the Humphrey field analyzer (HFA) in low vision
      Japanese subjects. Subjects were also divided into groups by diagnosis to examine
      how disease influences EDS measurements. METHODS: The EDS was obtained using GP
      (GP-EDS) and the built-in testing program of the HFA (HFA-EDS). Tests were
      performed within 3 months of each other. Regression analyses were used to examine
      the relationship between GP-EDS and HFA-EDS. RESULTS: A total of 128 visually
      impaired subjects were included in this study. Subjects had low vision because of
      glaucoma (57 subjects), age-related macular degeneration (AMD, 17 subjects),
      retinitis pigmentosa (RP, 17 subjects), and other causes (37 subjects). The GP
      EDS obtained was well-correlated with HFA-EDS (r = 0.87, P < 0.001) and it was
      possible to estimate HFA-EDS from GP-EDS. The GP-EDS was significantly lower than
      the HFA-EDS in eyes with glaucoma and RP. There was no significant difference
      between EDS values in eyes with AMD or other disease. CONCLUSION: The GP-EDS
      correlated well with the HFA-EDS. However, the relationship between the EDS
      measured with the two different testing modalities varies by disease.

PMID- 30212489
TI  - Socioeconomic determinants of rural women's desired fertility: A survey in rural
      Shaanxi, China.
AB  - There has been evidence demonstrating that China has had a persistently low and
      below-replacement level fertility since early 1990s, causing concerns of a
      rapidly aging population and sustainability of the Chinese economy. To avoid
      adverse effects of excessively low fertility, the Chinese government has recently
      changed its family planning policy from "one-child policy" to "two-child policy."
      Nonetheless, the effectiveness of the newly initiated two-child policy is
      questionable if women's average desired number of children or desired fertility
      for their lifetime is below the threshold fertility allowed by the two-child
      policy. Therefore, this study argues that it would be interesting and pertinent
      to know women's fertility desires under the circumstances of no policy
      restrictions and understand major factors that may affect their desired
      fertility. Based on a multi-stage stratified cluster sampling survey with 2,516
      women respondents in rural Shaanxi, this study tries to estimate desired
      fertility of rural women and evaluate the impact of important socioeconomic
      factors on their desired fertility. The results of this study reveal that the
      average lifetime desired fertility for rural women of childbearing age in Shaanxi
      is about 1.71, below the total fertility rate at the replacement level. The
      findings of this study suggest that women's marriage age, the pecuniary costs of
      having children, women's income forgone for having children, and social security
      benefits available for rural residents at retirement age, are significantly and
      negatively related to desired fertility. However, rural women's cultural views
      towards fertility are significantly but positively related to their desired
      fertility. This study further confirms that China has entered an era of low
      fertility, and thus, any policy restrictions on fertility may no longer be
      necessary. Instead, government programs which support childbearing and
      childrearing are needed to prevent excessive low fertility and rapid aging of the
      population.

PMID- 30212490
TI  - Treatment with placental growth factor attenuates myocardial ischemia/reperfusion
      injury.
AB  - Studies have established that oxidative stress plays an important role in the
      pathology of myocardial ischemia/reperfusion injury (MIRI). Vascular endothelial
      growth factor receptor 1 (VEGFR1) activation was reported to reduce oxidative
      stress and apoptosis. In the present study, we tested the hypothesis that the
      activation of VEGFR1 by placental growth factor (PlGF) could reduce MIRI by
      regulating oxidative stress. Mouse hearts and neonatal mouse cardiomyocytes were
      subjected to ischemia/reperfusion (I/R) and oxygen glucose deprivation (OGD),
      respectively. PlGF pretreatment markedly ameliorated I/R injury, as demonstrated
      by reduced infarct size and improved cardiac function. The protection was
      associated with a reduction of cardiomyocyte apoptosis. Similarly, our in vitro
      study showed that PlGF treatment improved cell viability and reduced
      cardiomyocyte apoptosis. Also, activation of VEGFR1 by PlGF suppressed
      intracellular and mitochondrial reactive oxygen species (ROS) generation.
      However, VEGFR1 neutralizing monoclonal antibody, which preventing PlGF binding,
      totally blocked this protective effect. In conclusion, activation of VEGFR1 could
      protect heart from I/R injury by suppression of oxidative stress and apoptosis.

PMID- 30212491
TI  - Pan-cancer inference of intra-tumor heterogeneity reveals associations with
      different forms of genomic instability.
AB  - Genomic instability is a major driver of intra-tumor heterogeneity. However,
      unstable genomes often exhibit different molecular and clinical phenotypes, which
      are associated with distinct mutational processes. Here, we algorithmically
      inferred the clonal phylogenies of ~6,000 human tumors from 32 tumor types to
      explore how intra-tumor heterogeneity depends on different implementations of
      genomic instability. We found that extremely unstable tumors associated with DNA
      repair deficiencies or high chromosomal instability are not the most
      intrinsically heterogeneous. Conversely, intra-tumor heterogeneity is greatest in
      tumors exhibiting relatively high numbers of both mutations and copy number
      alterations, a feature often observed in cancers associated with exogenous
      mutagens. Independently of the type of instability, tumors with high number of
      clones invariably evolved through branching phylogenies that could be stratified
      based on the extent of clonal (early) and subclonal (late) instability.
      Interestingly, tumors with high number of subclonal mutations frequently
      exhibited chromosomal instability, TP53 mutations, and APOBEC-related mutational
      signatures. Vice versa, mutations of chromatin remodeling genes often
      characterized tumors with few subclonal but multiple clonal mutations.
      Understanding how intra-tumor heterogeneity depends on genomic instability is
      critical to identify markers predictive of the tumor complexity and envision
      therapeutic strategies able to exploit this association.

PMID- 30212492
TI  - Characterization of EGF-guided MDA-MB-231 cell chemotaxis in vitro using a
      physiological and highly sensitive assay system.
AB  - Chemotactic cell migration is a central mechanism during cancer cell invasion and
      hence metastasis. In order to mimic in vivo conditions, we used a three
      dimensional hydrogel matrix made of collagen I and a stable gradient-generating
      chemotaxis assay system, which is commercially available (MU-Slide Chemotaxis) to
      characterize epidermal growth factor (EGF)-induced chemotaxis of the human breast
      cancer cell line MDA-MB-231. Surprisingly, chemotactic effects of EGF on MDA-MB
      231 cells could neither be observed in the standard growth medium DMEM/F-12
      supplemented with 10% serum nor in starvation medium. In contrast, after adapting
      the cells to the serum-free growth medium UltraCULTURETM, significant chemotactic
      effects could be measured with high sensitivity. The extremely time-stable linear
      gradients, generated in the chemotaxis chamber, led to consistent directional
      migration of MDA-MB-231 cells. Dose-response experiments showed increased
      directional and kinetic response of MDA-MB-231 cells towards stable gradients of
      EGF. While EGF-guided directional migration (chemotaxis) was highly concentration
      dependent with the highest response at 1.5 nM/mm EGF, we found that the
      chemokinetic effect induced by EGF was concentration-independent. Both, blocking
      the ligand-binding domain of the EGF receptor by an antibody (monoclonal anti
      EGFR antibody 225) and inhibition of its kinase domain by a small molecule
      inhibitor (AG1478) led to a reduction in EGF-induced directed migration. The high
      sensitivity of the assay even allowed us to observe synergistic effects in EGF
      receptor inhibition using a combination of low doses of both inhibitor types.
      Those results validate the fact that EGF is a potent guidance cue for MDA-MB-231
      cell migration and help to understand the mechanism behind chemotaxis-driven
      cancer metastasis.

PMID- 30212493
TI  - Effects of body habitus on contrast-induced acute kidney injury after
      percutaneous coronary intervention.
AB  - BACKGROUND: Limiting the contrast volume to creatinine clearance (V/CrCl) ratio
      is crucial for preventing contrast-induced acute kidney injury (CI-AKI) after
      percutaneous coronary intervention (PCI). However, the incidence of CI-AKI and
      the distribution of V/CrCl ratios may vary according to patient body habitus.
      OBJECTIVE: We aimed to identify the clinical factors predicting CI-AKI in
      patients with different body mass indexes (BMIs). METHODS: We evaluated 8782
      consecutive patients undergoing PCI and who were registered in a large Japanese
      database. CI-AKI was defined as an absolute serum creatinine increase of 0.3
      mg/dL or a relative increase of 50%. The effect of the V/CrCl ratio relative to
      CI-AKI incidence was evaluated within the low- (<=25 kg/m2) and high- (>25 kg/m2)
      BMI groups, with a V/CrCl ratio > 3 considered to be a risk factor for CI-AKI.
      RESULTS: A V/CrCl ratio > 3 was predictive of CI-AKI, regardless of BMI (low-BMI
      group: odds ratio [OR], 1.77 [1.42-2.21]; P < 0.001; high-BMI group: OR, 1.67
      [1.22-2.29]; P = 0.001). The relationship between BMI and CI-AKI followed a
      reverse J-curve relationship, although baseline renal dysfunction (creatinine
      clearance <60 mL/min, 46.9% vs. 21.5%) and V/CrCl ratio > 3 (37.3% vs. 20.4%)
      were predominant in the low-BMI group. Indeed, low BMI was a significant
      predictor of a V/CrCl ratio > 3 (OR per unit decrease in BMI, 1.08 [1.05-1.10]; P
      < 0.001). CONCLUSIONS: A V/CrCl ratio > 3 was strongly associated with the
      occurrence of CI-AKI. Importantly, we also identified a tendency for physicians
      to use higher V/CrCl ratios in lean patients. Thus, recognizing this trend may
      provide a therapeutic target for reducing the incidence of CI-AKI.

PMID- 30212494
TI  - Exploiting hot-spots; effective determination of lichen diversity in a Carpathian
      virgin forest.
AB  - Although lichenized fungi are among the most reliable indicators of forest
      quality and represent a considerable part of forest biodiversity, methods
      maximizing completeness of their species lists per area are lacking. Employing a
      novel methodological approach including a multi-expert competition and a search
      for local hot-spot plots, we have obtained outstanding data about epiphytic
      lichen biota in a part of the largest Central European virgin forest reserve
      Uholka-Shyrokyi Luh situated in Ukrainian Carpathians. Our field research
      consisted of two four-day periods: (1) an overall floristic survey and a search
      for spots with raised lichen diversity, and (2) survey in four one-hectare plots
      established in lichen diversity hot-spots along an altitudinal gradient. Recorded
      alpha-diversities in plots ranged from 181-228 species, but estimated species
      richness is in the range 207-322 species. Detected gamma-diversity was 387
      species; estimates are 409-484 species. 93% of the species found in the forest
      were recorded in plots, but only 65% outside the plots. This underlines the high
      efficiency of the multi-expert competitive survey in diversity hot-spot plots.
      Species richness in each one-hectare plot was equal to the numbers of species
      obtained by floristic surveys of much larger old-growth forest areas in Central
      Europe. Gamma-diversity detected in the Uholka primeval forest far exceeded all
      numbers achieved in Central European old-growth forests. Our method appears to be
      both effective (it obtains a more nearly complete inventory of species) and
      practical (the resources required are not unreasonably large).

PMID- 30212495
TI  - Correction: Whole exome sequencing reveals HSPA1L as a genetic risk factor for
      spontaneous preterm birth.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1007394.].

PMID- 30212496
TI  - Long-lasting insecticidal net use and asymptomatic malaria parasitaemia among
      household members of laboratory-confirmed malaria patients attending selected
      health facilities in Abuja, Nigeria, 2016: A cross-sectional survey.
AB  - INTRODUCTION: In Nigeria, malaria remains a major burden. There is the
      presupposition that household members could have common exposure to malaria
      parasite and use of long-lasting insecticidal net (LLIN) could reduce
      transmission. This study was conducted to identify factors associated with
      asymptomatic malaria parasitaemia and LLIN use among households of confirmed
      malaria patients in Abuja, Nigeria. METHODS: A cross-sectional survey was
      conducted from March to August 2016 in twelve health facilities selected from
      three area councils in Abuja, Nigeria. Participants were selected using multi
      stage sampling technique. Overall, we recruited 602 participants from 107
      households linked to 107 malaria patients attending the health facilities. Data
      on LLIN ownership, utilization, and house characteristics were collected using a
      semi-structured questionnaire. Blood samples of household members were examined
      for malaria parasitaemia using microscopy. Data were analyzed using descriptive
      statistics, Chi-square, and logistic regression (alpha = 0.05). RESULTS: Median
      age of respondents was 16.5 years (Interquartile range: 23 years); 55.0% were
      females. Proportions of households that owned and used at least one LLIN were
      44.8% and 33.6%, respectively. Parasitaemia was detected in at least one family
      member of 102 (95.3%) index malaria patients. Prevalence of asymptomatic malaria
      parasitaemia among study participants was 421/602 (69.9%). No association was
      found between individual LLIN use and malaria parasitaemia (odds ratio: 0.9, 95%
      confidence interval (95%CI): 0.6-1.3) among study participants. Having bushes
      around the homes was associated with having malaria parasitaemia (adjusted OR
      (aOR): 2.7, 95%CI: 1.7-4.2) and less use of LLIN (aOR: 0.4, 95%CI: 0.2-0.9).
      Living in Kwali (aOR: 0.1, 95% CI: 0.0-0.2) was associated with less use of LLIN.
      CONCLUSION: High prevalence of asymptomatic malaria and low use of LLIN among
      household members of malaria patients portend the risk of intra-household common
      source of malaria transmission. We recommend household health education on LLIN
      use and environmental management. Study to explore the role of preventive
      treatment of household members of confirmed malaria patient in curbing
      transmission is suggested. Strategies promoting LLIN use need to be intensified
      in Kwali.

PMID- 30212497
TI  - Influence of supply-side factors on voluntary medical male circumcision costs in
      Kenya, Rwanda, South Africa, and Zambia.
AB  - BACKGROUND: In this study, we described facility-level voluntary medical male
      circumcision (VMMC) unit cost, examined unit cost variation across facilities,
      and investigated key facility characteristics associated with unit cost
      variation. METHODS: We used data from 107 facilities in Kenya, Rwanda, South
      Africa, and Zambia covering 2011 or 2012. We used micro-costing to estimate
      economic costs from the service provider's perspective. Average annual costs per
      client were estimated in 2013 United States dollars (US$). Econometric analysis
      was used to explore the relationship between VMMC total and unit cost and
      facility characteristics. RESULTS: Average VMMC unit cost ranged from US$66 (SD
      US$79) in Kenya to US$160 (SD US$144) in South Africa. Total cost function
      estimates were consistent with economies of scale and scope. We found a negative
      association between the number of VMMC clients and VMMC unit cost with a 3%
      decrease in unit cost for every 10% increase in number of clients and we found a
      negative association between the provision of other HIV services and VMMC unit
      cost. Also, VMMC unit cost was lower in primary health care facilities than in
      hospitals, and lower in facilities implementing task shifting. CONCLUSIONS:
      Substantial efficiency gains could be made in VMMC service delivery in all
      countries. Options to increase efficiency of VMMC programs in the short term
      include focusing service provision in high yield sites when demand is high,
      focusing on task shifting, and taking advantage of efficiencies created by
      integrating HIV services. In the longer term, reductions in VMMC unit cost are
      likely by increasing the volume of clients at facilities by implementing
      effective demand generation activities.

PMID- 30212498
TI  - Accuracy of four digital scanners according to scanning strategy in complete-arch
      impressions.
AB  - STATEMENT OF PROBLEM: Although there are specific and general digital scanning
      guidelines depending on the system used, it is important to have the necessary
      flexibility in the acquisition of three-dimensional (3D) images to adapt to any
      clinical situation without affecting accuracy. PURPOSE: The purpose of this in
      vitro study was to identify and compare the scanning strategy with the greatest
      accuracy, in terms of trueness and precision, of four intraoral scanners in the
      impression of a complete dental arch. MATERIAL AND METHODS: Four digital scanners
      were evaluated with a 3D measuring software, using a highly accurate reference
      model obtained from an industrial scanner as a comparator. Four scanning
      strategies were applied 10 times on a complete maxillary arch cast inside a black
      methacrylate box. The data were statistically analyzed using one-way analysis of
      variance (ANOVA) and post hoc comparisons with Tamhane T2 test. RESULTS: The
      trueness of the Trios and iTero system showed better results with strategy "D,"
      Omnicam with strategy "B," and True Definition with strategy "C". In terms of
      precision, both iTero and True Definition showed better results with strategy
      "D", while Trios showed best results with strategy "A" and Omnicam with strategy
      "B". There were significant differences between the scanning strategies (p<0.05)
      with the iTero scanner, but not with the other scanners (p>0.05). CONCLUSIONS:
      The digital impression systems used in the experiment provided sufficient
      flexibility for the acquisition of 3D images without this affecting the accuracy
      of the scanner.

PMID- 30212499
TI  - A Bayesian framework for efficient and accurate variant prediction.
AB  - There is a growing need to develop variant prediction tools capable of assessing
      a wide spectrum of evidence. We present a Bayesian framework that involves
      aggregating pathogenicity data across multiple in silico scores on a gene-by-gene
      basis and multiple evidence statistics in both quantitative and qualitative
      forms, and performs 5-tiered variant classification based on the resulting
      probability credible interval. When evaluated in 1,161 missense variants, our
      gene-specific in silico model-based meta-predictor yielded an area under the
      curve (AUC) of 96.0% and outperformed all other in silico predictors.
      Multifactorial model analysis incorporating all available evidence yielded 99.7%
      AUC, with 22.8% predicted as variants of uncertain significance (VUS). Use of
      only 3 auto-computed evidence statistics yielded 98.6% AUC with 56.0% predicted
      as VUS, which represented sufficient accuracy to rapidly assign a significant
      portion of VUS to clinically meaningful classifications. Collectively, our
      findings support the use of this framework to conduct large-scale variant
      prioritization using in silico predictors followed by variant prediction and
      classification with a high degree of predictive accuracy.

PMID- 30212500
TI  - Women's perception about contraceptive use benefits towards empowerment: A
      phenomenological study in Southern Ethiopia.
AB  - BACKGROUND: Despite the availability of copious information regarding
      contraceptive use benefits and the factors that influence the uptake of the
      services, there is little evidence revealing the lived experiences of rural
      women. Thus, this study was conducted with the purpose of exploring the lived
      experiences of women regarding contraceptive use and related benefits towards
      women's empowerment. METHODS: Interpretative phenomenological qualitative
      methodology was employed to explore the lived experiences of women. Data were
      collected through focus group discussions and in-depth individual interviews and
      analyzed using an interpretive phenomenological framework including phases of
      data immersion, transcribing, coding, theme development and phenomenological
      interpretation through hermeneutic circle. RESULT: The reported lived experiences
      of rural women revealed that their livelihoods greatly improved in different ways
      after they began to use contraceptives. The benefits included securing more time,
      energy and social engagements. Contraceptive use helped women postpone unwanted
      pregnancies and child births and engage in various income generation activities
      that not only boosted family incomes but also created opportunity to mobilize the
      resources for different expenses without waiting for the handouts from their
      husbands. The women's experiences also indicated that contraceptive use improved
      the educational status of their daughters and they experienced improved self
      image, better social standing and improved family relations. The experiences
      further illustrated that contraceptive use was not only emancipatory and
      transformative, but also created peace and stability in their lives. CONCLUSION:
      The study concludes that contraceptive use, which is part of a woman's life
      experience, created remarkable opportunities and achievements. One of these was
      that women were able to control their bodies, reproduction and fertility which
      resulted in a higher degree of empowerment. The control of reproduction and
      fertility has liberated them from worries and entrapment of unplanned and
      unwanted pregnancies. Moreover, contraceptive use led to wider opportunities in
      the community, by improving their status and building a sense of empowerment.
      Creating awareness around the benefits of contraceptive use has the potential to
      improve community and national development. Based on the result, the study
      recommends that systems should be established to capitalize on the lessons
      learned about the lives of current users and expand the remarkable achievements
      and experiences to non-user counterparts.

PMID- 30212501
TI  - 2018 PLOS Genetics Research Prize: Bundling, stabilizing, organizing-The
      orchestration of acentriolar spindle assembly by microtubule motor proteins.

PMID- 30212502
TI  - Risk factors associated with obstructive sleep apnea-hypopnea syndrome in Chinese
      children: A single center retrospective case-control study.
AB  - Pediatric obstructive sleep apnea-hypopnea syndrome is caused by multiple
      factors. The present study aimed to investigate the potential risks of pediatric
      obstructive sleep apnea hypopnea syndrome (OSAHS) and their correlation with the
      disease severity. A total of 338 pediatric patients with OSAHS (polysomnography
      (PSG) diagnosis) were enrolled between June 2008 and October 2010. These
      pediatric patients were divided into mild, moderate and severe subgroups
      according to the obstructive apnea index (OAI) and/or apnea hypoventilation index
      (AHI). A total of 338 pediatric patients with vocal nodules who were without
      obstruction of the upper respiratory tract were enrolled as the control group.
      The patients were analyzed retrospectively. The average number of upper
      respiratory tract infections each year and tonsil hypertrophy, adenoid
      hypertrophy, positive serum tIgE, chronic sinusitis, nasal stenosis, craniofacial
      features and obesity were significantly higher in OSAHS compared with controls
      (P<0.01). The parameters the average number of upper respiratory tract infections
      each year (OR: 1.395, 95% CI: 1.256-1.550), adenoid hypertrophy (OR: 8.632, 95%
      CI: 3.990-18.672), tonsil hypertrophy (OR: 9.138, 95% CI: 4.621-18.073), nasal
      stenosis (8.023, 95% CI: 3.633-17.717) and chronic sinusitis (OR: 27.186, 95% CI:
      13.310-55.527) were independent factors of pediatric OSAHS (P<0.01). The
      distribution of chronic sinusitis, nasal stenosis, craniofacial features and
      obesity indicated a gradual increasing trend in the severity of OSAHS (P<0.01).
      Number of upper respiratory tract infections per year, adenoid hypertrophy,
      tonsil hypertrophy, chronic sinusitis, nasal stenosis, infections, allergic
      reactions, craniofacial features and obesity may be potential risk factors of
      pediatric OSAHS.

PMID- 30212503
TI  - Transcriptional response of rice flag leaves to restricted external phosphorus
      supply during grain filling in rice cv. IR64.
AB  - Plant phosphorus (P) remobilisation during leaf senescence has fundamental
      implications for global P cycle fluxes. Hypothesising that genes involved in
      remobilisation of P from leaves during grain filling would show altered
      expression in response to P deprivation, we investigated gene expression in rice
      flag leaves at 8 days after anthesis (DAA) and 16 DAA in plants that received a
      continuous supply of P in the nutrient solution vs plants where P was omitted
      from the nutrient solution for 8 consecutive days prior to measurement. The
      transcriptional response to growth in the absence of P differed between the early
      stage (8 DAA) and the later stage (16 DAA) of grain filling. At 8 DAA, rice
      plants maintained production of energy substrates through upregulation of genes
      involved in photosynthesis. In contrast, at 16 DAA carbon substrates were
      produced by degradation of structural polysaccharides and over 50% of highly
      upregulated genes in P-deprived plants were associated with protein degradation
      and nitrogen/amino acid transport, suggesting withdrawal of P from the nutrient
      solution led to accelerated senescence. Genes involved in liberating inorganic P
      from the organic P compounds and vacuolar P transporters displayed differential
      expression depending on the stage of grain filling stage and timing of P
      withdrawal.

PMID- 30212504
TI  - Participation experiences of people with deafblindness or dual sensory loss: A
      scoping review of global deafblind literature.
AB  - BACKGROUND: Deafblindness, also known as dual sensory loss, is a varying
      combination of visual and hearing impairment in the same individual. Interest in
      this topic has increased recently due to evidence suggesting an increase in
      prevalence of this condition among older adults. Persons with deafblindness
      frequently experience participation barriers and social isolation. Developing an
      understanding of their experiences can inform the design of programs and policies
      to enhance participation of people with deafblindness in society. OBJECTIVE: To
      identify and summarize available research literature on participation experiences
      of people with deafblindness or dual sensory loss. METHODS: A comprehensive
      literature search of eight databases (CINAHL/EBSCO, Embase, ERIC, Global Health,
      MEDLINE, ProQuest, PsycINFO, PubMed) was performed in accordance with the
      Preferred Reporting Items for Systematic Reviews (PRISMA) during January 2017 and
      last updated in June 2017. In addition, non-peer reviewed (grey) literature was
      also retrieved in the form of online published reports of research projects by 16
      deafblind-specific organizations across the globe. To be included, sources had to
      be published after 1990, had persons with deafblindness as the focal population,
      and focused on their participation experiences. RESULTS: A total 1172 sources
      were identified of which 54 studies were included. The findings reveal that
      persons with deafblindness, regardless of origin of their impairment, experience
      difficulty in communication, mobility, daily living functioning, and social
      interactions. While these experiences may vary between individuals with
      congenital versus acquired conditions, they generally feel socially isolated,
      insecure and uncertain about their future. CONCLUSION: Participation experiences
      of persons with deafblindness are shaped by dynamic interactions between personal
      factors (such as onset and type of impairments) and environmental influences
      (such as attitude, technology, and supports). A better understanding of
      participation experiences may help professionals in placing emphasis on affected
      participation domains to design services to enhance participation of people with
      deafblindness.

PMID- 30212505
TI  - Evaluation of Xpert MTB/RIF assay for detection of Mycobacterium tuberculosis in
      stool samples of adults with pulmonary tuberculosis.
AB  - BACKGROUND: The Xpert MTB/RIF (Xpert) assay technology allows rapid and sensitive
      diagnosis of pulmonary tuberculosis (PTB) from sputum specimens. However,
      diagnosis of PTB is difficult for patients who cannot produce sputum. The
      objective of this study was to investigate the use of Xpert assay for successful
      detection of PTB using stool samples from adult subjects. METHODS: Both stool and
      sputum samples from known smear and Xpert positive PTB patients were collected
      from a TB hospital in Dhaka. Stool samples were collected from healthy
      individuals without TB symptoms from a slum area of Dhaka. Stool and sputum
      samples were decontaminated and concentrated using NALC-NaOH-Na-citrate solution
      and the resultant sediment was used for Xpert, acid-fast bacilli (AFB) microscopy
      and culture. RESULTS: A total of 102 stool samples were collected from PTB
      patients and another 50 stool samples from healthy individuals without TB. The
      sensitivity of the Xpert assay for detection of M. tuberculosis in stool samples
      of PTB patients was 90.2% (95% CI, 82.9-95.0). All 50 stool samples from healthy
      individuals were negative by the assay (Specificity 100%; 95% CI, 92.9-100).
      Compared with the sputum culture positive results the sensitivity of the stool
      Xpert assay was 94.8% (95% CI, 88.5-97.8). Moreover, stool Xpert demonstrated
      full concordant results with the sputum culture for detection of rifampicin
      susceptibility. The cycle threshold values of rpoB probes obtained from Xpert
      assay correlated significantly with the bacilli load in the corresponding stool
      (Spearman correlation = -0.40, P < 0.01) and sputum (Spearman correlation = 
      0.77, P < 0.01) samples as determined by microscopy. CONCLUSIONS: Stool Xpert can
      be applied as a potential alternative of sputum testing for detection of M.
      tuberculosis and accurate determination of RIF susceptibility in adult PTB
      patients. The assay would be beneficial for rapid diagnosis of PTB for those
      adult patients who cannot expectorate sputum.

PMID- 30212506
TI  - Post-operative immune suppression is mediated via reversible, Interleukin-10
      dependent pathways in circulating monocytes following major abdominal surgery.
AB  - INTRODUCTION: Post-operative infections occur frequently following major surgery.
      The magnitude of the post-operative immune response is associated with an
      increased risk of post-operative infections, although the mechanisms driving post
      operative immune-dysfunction and the potential reversibility of this response
      with immune stimulants are not well understood. This study aims to describe the
      immediate immune response to major surgery and establish links to both post
      operative infection and functional aspects of immune dysregulation. We also
      investigate the potential of clinically available immune stimulants to reverse
      features of post-operative immune-dysfunction. METHODS: Patients over 45 years
      old undergoing elective gastro-intestinal surgery with planned post-operative
      surgical ICU admission were recruited. The expression of selected genes was
      determined pre-operatively and at 2, 24 and 48 hours post-operatively using qRT
      PCR. Circulating levels of Interleukin-10 protein were determined by ELISA. Peri
      operative cell surface monocyte HLA-DR (mHLA-DR) expression was determined using
      flow cytometry. Gene expression and mHLA-DR levels were determined in healthy
      monocytes cultured in peri-operative serum with and without neutralising
      antibodies and immune stimulants. RESULTS: 119 patients were recruited; 44
      developed a post-operative infection. Interleukin-10 mRNA and protein increased 4
      fold post-operatively (P<0.0001), peaking within 2 hours of the procedure. Higher
      post-operative Interleukin-10 mRNA (P = 0.007) and protein (P = 0.001) levels
      were associated with an increased risk of infection. Cell surface mHLA-DR
      expression fell post-operatively (P<0.0001). Reduced production, rather than
      intracellular sequestration, accounted for the post-operative decline in cell
      surface mHLA-DR expression. Interleukin-10 antibody prevented the decrease in
      mHLA-DR expression observed when post-operative serum was added to healthy
      monocytes. GM-CSF and IFN-gamma prevented the decline in mHLA-DR production
      through distinct pathways. CONCLUSIONS: Monocyte dysfunction and features of
      immune suppression occur frequently after major surgery. Greater post-operative
      Interleukin-10 production is associated with later infection. Interleukin-10 is
      an important mediator of post-operative reductions in mHLA-DR expression, while
      clinically available immune stimulants can restore mHLA-DR levels.

PMID- 30212507
TI  - Variables associated with the oral impact on daily performance of adults in the
      state of Sao Paulo: A population-based study.
AB  - OBJECTIVE: This study aimed to assess the oral impact on daily performance and
      its association with sociodemographic characteristics, tooth pain, need for
      prosthesis, and periodontal disease of adults in the state of Sao Paulo, Brazil.
      METHODS: This was a cross-sectional epidemiological study with secondary data
      obtained from the Oral Health Conditions Project- 2015 conducted in 163
      municipalities in the state of Sao Paulo with the participation of 17,560
      individuals. This study evaluated adults in the age-range between 35-44 years (n
      = 5,855), selected by means of probabilistic cluster sampling in two stages. The
      outcome variable was the OIDP (Oral Impacts on Daily Performances), obtained by
      using this instrument to assess daily activities (eating, speaking, oral hygiene,
      relaxation, sports practice, smile, study/work, social contact, and sleep). The
      independent variables were collected and grouped into three blocks: Block 1 (sex,
      age group, and ethnic group); Block 2 (household income and education); and Block
      3 (tooth pain, need for prosthesis, bleeding, calculus, and periodontal pockets).
      A hierarchical multiple logistic regression analysis was performed considering
      the complex cluster sampling plan. Each observation was assigned a specific
      weight, depending on the location, which resulted in weighted frequencies
      adjusted for the effect of outlining. RESULTS: the female sex (p<0.0001), ethnic
      group black/mulatto (p<0.0001), low household income (p = 0.0112), up to 8 years
      of education (p<0.0001), tooth pain (p<0.0001), presence of bleeding (p<0.0001),
      and presence of periodontal pockets (p<0.0001) had greater oral impact on daily
      performance. CONCLUSION: sociodemographic characteristics, tooth pain, and
      presence of periodontal disease were associated with oral impact on daily
      performance of the adult population in the state of Sao Paulo, Brazil.

PMID- 30212508
TI  - The prevalence and associated factors of non-communicable disease risk factors
      among civil servants in Ibadan, Nigeria.
AB  - BACKGROUND: Non-communicable diseases (NCDs) have become a global public health
      problem, which threatens Sub-Sahara Africa (SSA) including Nigeria. Civil
      servants are at risk of NCDs because of the stressful and sedentary nature of
      their work. The study aimed to determine the prevalence and associated factors of
      the major risk factors of NCDs among civil servants in Ibadan, Nigeria. METHODS:
      A cross-sectional study was conducted among 606 civil servants in Oyo State using
      a two-stage cluster sampling technique. The WHO Stepwise approach was used to
      assess the behavioural and metabolic risk factors. Anthropometric (weight,
      height, waist and hip circumferences), blood pressure and biochemical
      measurements (fasting blood sugar) were obtained. Prevalence rates and 95%
      confidence intervals were calculated. Multivariate logistic models with adjusted
      odds ratios and their 95% confidence intervals were used to assess the associated
      factors of NCD risk factors. Multiple Poisson regression was also performed to
      determine the effects of certain socio-demographic factors on the clustering of
      NCD risk factors. RESULTS: The mean age of the civil servants was 43.0+/-10.3 and
      53.8% were males. The prevalence estimates and 95% confidence intervals of the
      risk factors were 6.5% (95% CI:4.5-8.5) for current smoking, 7.8% (95% CI:5.1
      10.5) for harmful use of alcohol, 62.2% (95% CI:58.2-66.2) for low physical
      activity, 69.7% (95% CI:66.0-73.4) for insufficient fruit and vegetable intake,
      37.1% (95% CI:33.2-41.0) for abdominal obesity, 57.3% (95% CI:53.3-61.3) for
      overweight and obesity, 33.1% (95% CI:29.3-36.8) for raised blood pressure and
      7.1% (95% CI:5.0-9.1) for raised blood sugar. Over 75% of the population had at
      least two NCD risk factors and the study participants had an average of 3 NCD
      risk factors 3.01 (95% CI: 2.88-3.14) The female gender was significantly
      associated with an increased risk for abdominal obesity (AOR 27.9; 95% CI: 12.09
      64.6) and being overweight or obese (AOR 6.78; 95% CI: 3.53-13.01), but was
      protective of smoking (AOR 0.21; 95% CI: 0.07-0.61) and binge drinking (AOR 0.04;
      95% CI: 0.01-0.45). Also, the risk of hypertension increased with age- 30-39
      years (AOR 12.29; 95% CI: 1.06-141.8), 40-49 years (AOR 14.28; 95% CI: 1.10
      181.4) and 50 years and above (AOR 32.43; 95% CI: 2.44-413.7). Raised blood
      pressure was a strong correlate for having raised blood sugar (AOR 5.63; 95% CI:
      1.48-21.3). Increasing age (IRR 1.02; 95% CI: 1.01-1.02) and being female (IRR
      1.36; 95% CI: 1.23-1.49) were also important predictors of the clustering of risk
      factors. CONCLUSION: The feminization (i.e. the preponderance of risk factors
      among the females) and clustering of non-communicable disease risk factors were
      observed among Oyo State civil servants. Our findings highlight the high
      prevalence of cardio-metabolic risk factors among the working class. Hence the
      need for targeted preventive and therapeutic interventions among this population.

PMID- 30212510
TI  - Biodeterioration of plasma pretreated LDPE sheets by Pleurotus ostreatus.
AB  - Low-density polyethylene (LDPE) waste generates an environmental impact. To
      achieve the most suitable option for their degradation, it is necessary to
      implement chemical, physical and biological treatments, as well as combining
      procedures. Best treatment was prognosticated by Plackett-Burman Experimental
      Design (PB), evaluating five factors with two levels (0.25 mM or 1.0 gL-1
      glucose, 1.0 or 2.0 mM CuSO4, 0.1 or 0.2 mM ABTS [2, 20-azino-bis(3
      ethylbenzothiazoline-6-sulphonic acid)], pH 4.5 +/- 0.2 or 7.0 +/- 0.2 and 30 or
      90 day incubation), which was reproduced for 150 days. Therefore, PB identified a
      sequential treatment (plasma followed by fungus) for partial LDPE
      biodeterioration. Sheets were pretreated with glow discharge plasma (O2, 3.0 x 10
      2 mbar, 600 V, 6 min.), followed by Pleurotus ostreatus biodeterioration. Fungus
      growth, colonization percentage, and pigment generation followed. Laccase (Lac),
      manganese peroxidase (MnP) and lignin peroxidase (LiP) activities were appraised.
      Additionally, contact angle (CA), functional group presence and changes and
      carbonyl and vinyl indices (Fourier transformed infrared spectroscopy) were
      evaluated. LDPE surface changes were assessed by Young's modulus, yield strength,
      scanning electronic microscopy (SEM), Fourier transformed infrared spectroscopy
      (FTIR) and atomic force microscopy (AFM). Plasma discharge increased
      hydrophilicity, decreasing CA by 76.57% and increasing surface roughness by
      99.81%. P. ostreatus colonization was 88.72% in 150 days in comparison with
      untreated LDPE (45.55%). After this treatment carbonyl groups (C = O), C = C
      insaturations, high hydrophilicity CA (16 +/- 4)  degrees , and low surface
      roughness (7 +/- 2) nm were observed. However, the highest Lac and LiP activities
      were detected after 30 days (Lac: 2.817 U Lac g-1 and LiP: 70.755 U LiP g-1). In
      addition, highest MnP activity was observed at day 120 (1.097 U MnP g-1) only for
      P. ostreatus treated LDPE. Plasma favored P. ostreatus adsorption, adherence,
      growth and colonization (88.72%), as well as partial LDPE biodeterioration,
      supported by increased hydrophilicity and presence of specific functional
      chemical groups. The approximate 27% changes in LDPE physical properties support
      its biodeterioration.

PMID- 30212509
TI  - Does emotion regulation engage the same neural circuit as working memory? A meta
      analytical comparison between cognitive reappraisal of negative emotion and 2
      back working memory task.
AB  - Research into cognitive emotion regulation (ER) extends our understanding of
      human cognition, which is capable of processing objective information and is
      crucial in maintaining subjective/internal homeostasis. Among various ER
      strategies, the alleviation of negative emotion via reappraisal is of particular
      importance for adaptation and psychological well-being. Although still debated,
      previous neuroimaging studies tend to infer that the reappraisal ER is mediated
      by the capability of working memory (WM), which has not been examined
      empirically. This meta-analytical study of published neuroimaging literature used
      activation likelihood estimation (ALE) to compare the neural circuits that
      regulate negative emotion (reappraisal tasks; 46 studies/1254 subjects) and
      execute WM (2-back tasks; 50 studies/1312 subjects), with special emphasis on the
      prefrontal cortex (PFC). Taking the canonical WM network as a reference, ALE
      results revealed that the dorsal midline PFC was partly shared by both ER and WM,
      whereas ER-specific PFC structures were delineated in the inferior, middle, and
      superior frontal cortices, as well as in the posterior brain regions. The peak
      coordinates of ER in the middle frontal cortex were dorsal to those of WM by 15.1
      mm (left) and 21.6 mm (right). The results support specialized emotion-related
      neural substrates in the PFC, negating the assumption that reappraisal ER and WM
      rely on the same neural resources. The holistic picture of "emotional brain" may
      need to incorporate the emotion-related PFC circuit, together with subcortical
      and limbic emotion centers.

PMID- 30212512
TI  - Impact of mesoscale eddies on chlorophyll variability off the coast of Chile.
AB  - The mesoscale eddies off the coast of Chile significantly impact the distribution
      of local chlorophyll and the development of marine ecosystem. Multiple processes,
      including eddy trapping, pumping, advection, Ekman-pumping, and submesoscale
      dynamics, exert their impacts simultaneously on transport of water masses at
      different distances with respect to the eddy center. The cyclonic (anticyclonic)
      eddies are generally characterized by upwelling (downwelling) within the eddy,
      which elevates (depresses) chlorophyll inside the eddy. Outside the eddy
      periphery, multiple processes are involved simultaneously, but their
      corresponding influences on chlorophyll are not well identified. In this study,
      the amplitudes of cyclonic and anticyclonic eddies are distinguished as positive
      and negative values, respectively. A linear regression method is applied to seek
      the connection between eddy's amplitude and chlorophyll distribution at different
      locations w.r.t. the eddy center. The regression slope between eddy amplitude and
      chlorophyll anomaly is found to be negative in the eddy interior and along the
      periphery, which gradually changes to positive away from the periphery. The
      location where the response of chlorophyll to an eddy switches its sign is
      defined as the transition zone. The location of the transition zone varies with
      offshore distance and is impacted by topography, such as the presence of islands,
      which can change the dynamics of eddies. Thus, the distance from eddy center and
      offshore distance from coast should be taken into consideration when
      investigating their influences on nutrient transport and chlorophyll
      distribution.

PMID- 30212511
TI  - Are government incentives effective for avoided deforestation in the tropical
      Andean forest?
AB  - In order to ensure the provision of goods and services from forests, many
      governments have promoted less-traditional conservation initiatives such as
      programs of payments for ecosystem services called, more broadly, direct payments
      for conservation. The Socio Bosque Program (SBP) is a governmental program in
      Ecuador that directly provides economic incentives to rural families and local
      and indigenous communities who have voluntarily agreed to comply with some
      conservation activities. An impact evaluation method (matching) was used to
      assess the impact of the SBP between 2008 and 2014. This study revealed that on
      average, the SBP reduced deforestation by 1.5% in those forests that received the
      SBP's direct payment. These forests would have been deforested if the SBP had not
      been implemented. Assessment of the impact of the SBP on individual and
      collective contracts, using the matching method, revealed that 3.4% and roughly
      1% of the forest would have been deforested in the absence of the program,
      respectively. In other words, the protected area in the collective SBP was
      1,247,500 ha and, if the SBP had not been implemented, an area of 11,227 ha would
      have been lost between 2008 and 2014. The 165,700 ha protected by the individual
      SBP, it was estimated that 5,733 ha were not deforested due to the implementation
      of the conservation program. Conventional estimates of the impact of the SBP tend
      to overestimate avoided deforestation because they do not control for observable
      covariates that correlate with or affect both SBP participation and
      deforestation. The conclusions are robust, even given potential hidden biases.
      The present study demonstrated that the SBP serves to mitigate the effects of
      climate change, especially with those contracts that are intended for individual
      owners.

PMID- 30212513
TI  - Population-level HIV incidence estimates using a combination of synthetic cohort
      and recency biomarker approaches in KwaZulu-Natal, South Africa.
AB  - INTRODUCTION: There is a notable absence of consensus on how to generate
      estimates of population-level incidence. Incidence is a considerably more
      sensitive indicator of epidemiological trends than prevalence, but is harder to
      estimate. We used a novel hybrid method to estimate HIV incidence by age and sex
      in a rural district of KwaZulu-Natal, South Africa. METHODS: Our novel method
      uses an 'optimal weighting' of estimates based on an implementation of a
      particular 'synthetic cohort' approach (interpreting the age/time structure of
      prevalence, in conjunction with estimates of excess mortality) and biomarkers of
      'recent infection' (combining Lag-Avidity, Bio-Rad Avidity and viral load results
      to define recent infection, and adapting the method for age-specific incidence
      estimation). Data were obtained from a population-based cross-sectional HIV
      survey conducted in Mbongolwane and Eshowe health service areas in 2013. RESULTS:
      Using the combined method, we find that age-specific HIV incidence in females
      rose rapidly during adolescence, from 1.33 cases/100 person-years (95% CI:
      0.98,1.67) at age 15 to a peak of 5.01/100PY (4.14,5.87) at age 23. In males,
      incidence was lower, 0.34/100PY (0.00-0.74) at age 15, and rose later, peaking at
      3.86/100PY (2.52-5.20) at age 30. Susceptible population-weighted average
      incidence in females aged 15-29 was estimated at 3.84/100PY (3.36-4.40), in males
      aged 15-29 at 1.28/100PY (0.68-1.50) and in all individuals aged 15-29 at
      2.55/100PY (2.09-2.76). Using the conventional recency biomarker approach, we
      estimated HIV incidence among females aged 15-29 at 2.99/100PY (1.79-4.36), among
      males aged 15-29 at 0.87/100PY (0.22-1.60) and among all individuals aged 15-59
      at 1.66/100PY (1.13-2.27). DISCUSSION: HIV incidence was very high in women aged
      15-30, peaking in the early 20s. Men had lower incidence, which peaked at age 30.
      The estimates obtained from the hybrid method are more informative than those
      produced by conventional analysis of biomarker data, and represents a more
      optimal use of available data than either the age-continuous biomarker or
      synthetic cohort methods alone. The method is mainly useful at younger ages,
      where excess mortality is low and uncertainty in the synthetic cohort estimates
      is reasonably small. CONCLUSION: Application of this method to large-scale
      population-based HIV prevalence surveys is likely to result in improved incidence
      surveillance over methods currently in wide use. Reasonably accurate and precise
      age-specific estimates of incidence are important to target better prevention,
      diagnosis and care strategies.

PMID- 30212514
TI  - The effects of oral nutritional supplements in patients with maintenance dialysis
      therapy: A systematic review and meta-analysis of randomized clinical trials.
AB  - BACKGROUND/OBJECTIVE: This systematic review aims to determine the potential
      effects of oral nutritional supplements (ONS) in patients receiving maintenance
      dialysis therapy (MDT). METHODS: Electronic databases were searched without
      language limits through to July 2018. Randomized controlled trials (RCTs) that
      involved comparisons of ONS versus placebo or routine care are included in this
      meta-analysis. RevMan 5.3 statistical software was used for meta-analysis.
      RESULTS: 15 articles with 589 subjects were included in our study. There are
      insufficient comparable data of randomized trials to allow meta-analysis of
      mortality. Albumin levels may be improved by the macronutrient blends or
      protein/amino acid supplements in MDT patients. Compared with the control group,
      serum albumin levels and BMI in the ONS group were increased by 1.58 g/L (95% CI,
      0.52-2.63, P = 0.003; I2 = 85%) and 0.40 kg/m2 (95% CI, 0.10-0.71, P = 0.01; I2 =
      49%), respectively. In the subgroup analysis of patients receiving hemodialysis,
      albumin levels in ONS group were increased by 2.17 g/L (95% CI, 0.89-3.45,
      P<0.001; I2 = 90%). ONS may not influence serum phosphorus and potassium levels.
      CONCLUSIONS: Very low-quality evidence suggests that Short-term oral energy or
      protein/amino acid supplements may improve nutritional status by increasing serum
      albumin levels and BMI in MDT patients, without influence on serum potassium
      levels. High-quality and large RCTs, particularly regarding the effects of ONS on
      mortality and quality of life, are needed to further validate our findings.

PMID- 30212515
TI  - Building university-based boundary organisations that facilitate impacts on
      environmental policy and practice.
AB  - Responding to modern day environmental challenges for societal well-being and
      prosperity necessitates the integration of science into policy and practice. This
      has spurred the development of novel institutional structures among research
      organisations aimed at enhancing the impact of environmental science on policy
      and practice. However, such initiatives are seldom evaluated and even in cases
      where evaluations are undertaken, the results are rarely made publicly available.
      As such there is very little empirically grounded guidance available to inform
      other organisations in this regard. To help address this, the aim of this study
      is to evaluate the Baltic Eye Project at Stockholm University-a unique team
      consisting of researchers from different fields, science communicators,
      journalists and policy analysts-working collectively to support evidence-informed
      decision-making relating to the sustainable management of the Baltic Sea
      environment. Specifically, through qualitative interviews, we (1) identify the
      impacts achieved by the Baltic Eye Project; (2) understand the challenges and
      barriers experienced throughout the Baltic Eye Project; and (3) highlight the key
      features that are needed within research organisations to enhance the impact of
      science on policy and practice. Results show that despite only operating for
      three years, the Baltic Eye Project has achieved demonstrable impacts on a range
      of levels: impacts on policy and practice, impacts to individuals working within
      the organisation and impacts to the broader University. We also identify a range
      of barriers that have limited impacts to date, such as a lack of clear goals at
      the establishment of the Baltic Eye Project and existing metrics of academic
      impact (e.g. number of publications). Finally, based on the experiences of
      employees at the Baltic Eye Project, we identify the key organisational,
      individual, financial, material, practical, political, and social features of
      university-based boundary organisations that have impact on policy and practice.
      In doing so this paper provides empirically-derived guidance to help other
      research organisations increase their capacity to achieve tangible impacts on
      environmental policy and practice.

PMID- 30212516
TI  - Derivation and validation of a new visceral adiposity index for predicting
      visceral obesity and cardiometabolic risk in a Korean population.
AB  - OBJECTIVES: The visceral adiposity index (VAI), an indirect marker of visceral
      adipose tissue, serves as a model associated with cardiometabolic risk, but has
      limitations regarding the Asian population. We sought to develop a new VAI (NVAI)
      for the Korean population and compare it to VAI for prediction of atherosclerotic
      cardiovascular disease (ASCVD) risk and development of major cardiovascular
      diseases (CVD) and stroke. METHODS: Patients (969) who underwent visceral fat
      area measurement were analyzed. After exclusion, 539 patients (142 men, 397
      women) were randomly divided into internal (n = 374) and external validation (n =
      165) data set. The NVAI was developed using univariate and multivariate logistic
      regression with backward selection of predictors. Receiver operating
      characteristic (ROC) curve analysis and comparison of the area under the curve
      (AUC) verified the better predictor of ASCVD risk score. Additionally, nationwide
      population-based cross-sectional survey data (Korean National Health and
      Nutrition Examination Survey [KNHANES] 2008-2010, n = 29,235) was used to
      validate the NVAI's ability to predict ASCVD risk and major CVD and stroke.
      RESULTS: The NVAI better reflected visceral fat area in internal and external
      data sets, with AUCs of 0.911 (95% confidence interval [CI]: 0.882-0.940) and
      0.879 (95% CI: 0.828-0.931), respectively. NVAI better discriminated for ASCVD
      risk (AUC = 0.892, 95% CI: 0.846-0.938) compared to VAI (0.559, 95% CI: 0.439
      0.679). The NVAI also better predicted MI or angina, and stroke with AUCs of
      0.771 (95% CI: 0.752-0.789), and 0.812 (95% CI: 0.794-0.830), respectively,
      compared with waist circumference (WC), body mass index (BMI), TG to HDL ratio,
      and VAI via KNHANES, in a statistically significant manner. CONCLUSIONS: The NVAI
      has advantages as a predictor of visceral obesity and is significantly associated
      with ASCVD risks and development of major CVD and stroke in the Korean
      population. The NVAI could be a screening tool for improved risk estimation
      related to visceral obesity.

PMID- 30212517
TI  - Wheezing after the use of acetaminophen and or ibuprofen for first episode of
      bronchiolitis or respiratory tract infection.
AB  - BACKGROUND: Bronchiolitis sometimes triggers the development of subsequent
      recurrent wheezing. Treatment with either acetaminophen or ibuprofen during the
      initial episode may affect the occurrence of subsequent wheezing. MATERIALS AND
      METHODS: We did a retrospective study comparing the effect of prescribing
      acetaminophen, ibuprofen, or neither for a first episode of bronchiolitis on
      medical attendances for subsequent wheezing in infants younger than 12 months. We
      created our cohorts using California Medicaid data from 2003 to 2010. We used
      propensity score derived inverse probability weights to adjust for non-random
      drug assignment. We used robust negative binomial regression to model incident
      rate ratios (IRR) for medical attendances at 365, 30, and 14-day follow-up. We
      did similar analyses for the effect of antipyretics for a first medically
      attended upper respiratory tract infection (URI) on subsequent wheezing. RESULTS:
      Compared with no antipyretic, treatment with acetaminophen or ibuprofen for a
      first episode of bronchiolitis was associated with decreased wheezing at 365-day
      follow-up (IRR 0.18, 95% CI 0.15-0.22), and ibuprofen plus acetaminophen over
      ibuprofen (IRR at 0.12, 95% CI 0.05-0.32). The results were similar at 30 and 14
      day follow-up. Ibuprofen alone and ibuprofen plus acetaminophen were associated
      with decreased visits for subsequent wheezing at 365-day (IRR 0.79, 95% CI 0.68
      0.92), but not earlier timepoints, when compared with acetaminophen. A smaller
      effect was seen for ibuprofen at one year if prescribed for a URI (IRR 0.87, 95%
      CI 0.76-1.00) but not at earlier follow-up. CONCLUSION: Children who are
      prescribed antipyretics for a first episode of bronchiolitis may have less
      subsequent wheezing than those who are not. We found fewer visits for subsequent
      wheezing for those prescribed ibuprofen, and ibuprofen combined with
      acetaminophen, compared with acetaminophen alone.

PMID- 30212518
TI  - In vivo conversion of astrocytes into oligodendrocyte lineage cells with
      transcription factor Sox10; Promise for myelin repair in multiple sclerosis.
AB  - Recent studies demonstrate that astroglial cells can be directly converted into
      functional neurons or oligodendrocytes. Here, we report that a single
      transcription factor Sox10 could reprogram astrocytes into oligodendrocyte-like
      cells, in vivo. For transdifferentiation, Sox10-GFP expressing viral particles
      were injected into cuprizone-induced demyelinated mice brains after which we
      assessed for the presence of specific oligodendrocyte lineage cell markers by
      immunohistofluorescence (IHF). As control, another group of demyelinated mice
      received GFP expressing viral particles. After 3 weeks, the majority of
      transduced (GFP+) cells in animals which received control vector were astrocytes,
      while in animals which received Sox10-GFP vector, the main population of GFP+
      cells were positive for oligodendrocyte lineage markers. We also extracted
      primary astrocytes from mouse pups and purified them. Primary astrocytes were
      transduced in vitro and then transplanted into demyelinated brains for later fate
      mapping. After three weeks, in vitro transduced and then transplanted astrocytes
      showed oligodendrocyte progenitor and mature oligodendrocyte markers. Further
      confirmation was done by transduction of astrocytes with lentiviral particles
      that expressed Sox10 and GFP and their culture in the oligodendrocyte progenitor
      medium. The induced cells expressed oligodendrocyte progenitor cells (iOPCs)
      markers. Our findings showed the feasibility of reprogramming of astrocytes into
      oligodendrocyte-like cells in vivo, by using a single transcription factor,
      Sox10. This finding suggested a master regulatory role for Sox10 which enabled
      astrocytes to change their fate to OPC-like cells and establish an
      oligodendroglial phenotype. We hope this approach lead to effective myelin repair
      in patients suffering from myelination deficit.

PMID- 30212519
TI  - Gender differences in factors associated with prehypertension and hypertension in
      Nepal: A nationwide survey.
AB  - BACKGROUND: Nepal has one of the highest prevalence of hypertension in South
      Asia. However, no national studies have examined the gender differences in the
      determinants of prehypertension and hypertension in the country to inform
      targeted interventions. This study aimed to investigate gender differences in
      factors associated with prehypertension and hypertension in Nepal using the 2016
      Nepal Demographic and Health Survey (NDHS). METHODS: Sociodemographic,
      behavioural, anthropometric and health status data and information on
      hypertension were obtained from 14,857 (males: 6,245 and females: 8,612)
      individuals aged 15 years or above from the biomarker sample of the 2016 NDHS.
      Factors associated with prehypertension and hypertension by gender were
      investigated using generalized linear latent and mixed models (GLLAM) with the
      mlogit link and binomial family that adjusted for clustering and sampling
      weights. RESULTS: The overall prevalence of prehypertension and hypertension was
      26.9% [95% confidence interval (CI): 25.7, 28.1] and 17.2% (95% CI 16.1, 18.3),
      respectively. Prehypertension was present in 30.4% (95%CI: 28.7, 32.2) of males
      and 24.3% (95% CI: 23.1, 25.6) of females, while hypertension was present in
      20.4%, (95% CI 18.9, 22.0) of males and 14.8% (95% CI: 13.7, 16.0) of females.
      Key modifiable factors that were strongly associated with prehypertension and
      hypertension in both genders included overweight and obesity, caffeine intake,
      tobacco use, no schooling, previously informed of hypertension in a health
      facility, and alcohol consumption (for males). Other significant factors
      associated with prehypertension and hypertension included increasing age (> 30
      years), ecological zone (Hill), Developmental zone (Western) and being married.
      CONCLUSION: Our results suggest that prehypertension and hypertension were higher
      in males compared to females. Interventions to improve awareness, screening,
      treatment and control of prehypertension and hypertension in Nepal are warranted
      and should target key modifiable factors, as well as people aged 30 years and
      above.

PMID- 30212520
TI  - Longitudinal anthropometry of children and adolescents using 3D-body scanning.
AB  - 3D-body scanning anthropometry is a suitable method for characterization of
      physiological development of children and adolescents, and for understanding
      onset and progression of disorders like overweight and obesity. Here we present a
      novel body typing approach to describe and to interpret longitudinal 3D-body
      scanning data of more than 800 children and adolescents measured in up to four
      follow-ups in intervals of 1 year, referring to an age range between 6 and 18
      years. We analyzed transitions between body types assigned to lower-, normal- and
      overweight participants upon development of children and adolescents. We found a
      virtually parallel development of the body types with only a few transitions
      between them. Body types of children and adolescents tend to conserve their
      weight category. 3D body scanning anthropometry in combination with body typing
      constitutes a novel option to investigate onset and progression of obesity in
      children.

PMID- 30212522
TI  - A qualitative study of motivations for meditation in anthroposophic
      practitioners.
AB  - Research on meditation is advancing, but few studies about the motivations of
      meditators exist. Additionally, many forms and traditions of meditation have yet
      to be investigated. This study addresses both of these issues by presenting an
      overview of different forms of motivations found in contemporary Anthroposophic
      meditation practice. 30 Anthroposophic meditators were interviewed about their
      meditation experiences. The interviews were examined using thematic analysis. 14
      data-driven themes were extracted and organized within a framework consisting of
      three superordinate theory-driven forms of motivation: External, internal and
      service. A developmental trajectory running from external and internal to service
      motivations is indicated. This approach improves upon a scheme developed by
      Shapiro by including additional types of motivations and being able to
      differentiate between forms of motivations that are fundamentally different: Self
      related (heteronomous and autonomous) motivations and other-related motivations.

PMID- 30212521
TI  - Impact of violacein from Chromobacterium violaceum on the mammalian gut
      microbiome.
AB  - Violacein is a violet pigment produced by Chromobacterium violaceum that
      possesses several functions such as antibacterial, antiviral, antifungal, and
      antioxidant activities. The search for potential compounds and therapies that may
      interfere with and modulate the gut microbial consortia without causing severe
      damage and increased resistance is important for the treatment of inflammatory,
      allergic, and metabolic diseases. The aim of the present work was to evaluate the
      ability of violacein to change microbial patterns in the mammalian gut by
      favoring certain groups over the others in order to be used as a therapy for
      diseases associated with changes in the intestinal microflora. To do this, we
      used male Wistar rats, and administered violacein orally, in low (50 MUg/ml) and
      high (500 MUg/ml) doses for a month. Initially, the changes in the microbial
      diversity were observed by DGGE analyses that showed that the violacein
      significantly affects the gut microbiota of the rats. Pyrosequencing of 16S rDNA
      was then employed using a 454 GS Titanium platform, and the results demonstrated
      that higher taxonomic richness was observed with the low violacein treatment
      group, followed by the control group and high violacein treatment group.
      Modulation of the microbiota at the class level was observed in the low violacein
      dose, where Bacilli and Clostridia (Firmicutes) were found as dominant. For the
      high violacein dose, Bacilli followed by Clostridia and Actinobacteria were
      present as the major components. Further analyses are crucial for a better
      understanding of how violacein affects the gut microbiome and whether this change
      would be beneficial to the host, providing a framework for the development of
      alternative treatment strategies for intestinal diseases using this compound.

PMID- 30212523
TI  - College-aged women in the United States that play overhand throwing sports have
      masculine digit ratios.
AB  - Athletic prowess in both males and females is negatively correlated with the
      ratio between the lengths of the second and fourth fingers (2D:4D), a correlate
      of prenatal testosterone exposure. Because multiple lines of evidence suggest
      that prenatal testosterone exposure is associated with sports interest,
      motivation, and athletic performance we measured the digit ratios of 77 non
      athletes, 103 varsity athletes, and 78 club sport athletes to test 8 hypotheses
      about the relationship between digit ratio and the athletic behavior of college
      age women in the USA. Using independent samples t-tests, we found no significant
      differences between the digit ratios of women that (1) were athletes and non
      athletes, (2) were varsity or club sport athletes, (3) had played or were
      currently playing individual or team sports, (4) played contact and non-contact
      sports, (5) played sports involving a ball and those that do not, (6) played
      sports where the outcome was determined by a score or the outcome of direct
      physical competition or subjectively by judges, or (7) were starters or reserves
      on their teams. However, women that played overhand throwing sports softball and
      water polo had significantly smaller digit ratios than did women that played
      other sports. These differences were not due to scaling effects. The independent
      samples t-test results were supported by subsequent Monte Carlo bootstrap,
      Bayesian, Random Forest, and multiple linear regression analyses. We suggest that
      the organizational consequences of prenatal testosterone exposure may influence
      the anatomy and physiology of women that leads to success playing overhand
      throwing sports.

PMID- 30212524
TI  - Reduced length of stay and hospitalization costs among inpatient hysterectomy
      patients with postoperative pain management including IV versus oral
      acetaminophen.
AB  - OBJECTIVE: To compare the outcomes of hysterectomy patients who received standard
      pain management including IV acetaminophen (IV APAP) versus oral APAP. METHODS:
      We performed a retrospective analysis of the Premier Database (January 2012 to
      September 2015) comparing hysterectomy patients who received postoperative pain
      management including IV APAP to those who received oral APAP starting on the day
      of surgery and continuing up to the third post-operative day, with no exclusions
      based on additional pain management. We compared the groups on length of stay
      (LOS), hospitalization costs, and average daily morphine equivalent dose (MED).
      The quarterly rate of IV APAP use for all hospitalizations by hospital was used
      as an instrumental variable in two-stage least squares regressions also adjusting
      for patient demographics, clinical risk factors, and hospital characteristics.
      RESULTS: We identified 22,828 hysterectomy patients including 14,811 (65%) who
      had received IV APAP. Study subjects averaged 50 and 52 years of age,
      respectively in the IV APAP and oral APAP cohorts and were predominantly non
      Hispanic Caucasians (>=60% in both cohorts). Instrumental variable models found
      IV APAP associated with 0.8 days shorter hospitalization (95% CI: -0.92 to -0.68,
      p<0.0001) and $2,449 lower hospitalization costs (95% CI: -$2,902 to -$1,996,
      p<0.0001). Average daily MED trended lower without statistical significance (
      1.41 mg, 95% CI: -3.43 mg to 0.61 mg, p = 0.17). CONCLUSIONS: Compared to oral
      APAP, managing post-hysterectomy pain with IV APAP is associated with shorter LOS
      and lower total hospitalization costs.

PMID- 30212525
TI  - Performance and usability evaluation of the INSTI HIV self-test in Kenya for
      qualitative detection of antibodies to HIV.
AB  - BACKGROUND: HIV testing is often undermined by lack of confidentiality, stigma,
      shortage of counselors and long distances to testing centers. Self-testing has
      the potential to circumvent these constraints. OBJECTIVE: To determine the
      performance and usability characteristics of the INSTI(r) HIV-1/HIV-2 Self-Test.
      METHODS: The performance evaluation was a cross sectional study and the usability
      a mixed methods study. For method comparison, Bioelisa HIV-1+2 Ag/Ab test was
      used as the reference test. When the test results were discrepant, results from
      Alere DetermineTM HIV-1/2 and First Response HIV-1-2 Antibody tests were used for
      confirmation of status. RESULTS: Sensitivity of the INSTI HIV Self-Test was
      98.99% (95% CI 96.05-99.75%), and specificity 98.15% (95% CI 95.63-99.23%). The
      concordance was therefore 97.27%. A total of 354 participants took part in the
      usability study. Of those, 343 (98.00%) found instructions for use easy to
      follow, 330 (94.29%) found the finger prick device easy to use, 303 (86.57%) were
      confident while performing the test, 342 (97.71%) felt result interpretation was
      easy, while 304 (86.86%) declared results within the recommended five minutes.
      Three hundred and forty two (342, 97.71%) were willing to use the test again
      while 344 (98.29%) would recommend the kit to a sexual partner. None of the 350
      participants quit the process at any stage. Three hundred and eighteen (318,
      91.12%) participants felt the test needed no further improvement. All 91 lay
      users correctly identified cartridges that showed positive, negative and invalid
      results. Only 31 (34.07%) participants correctly identified weak positive dummy
      test results. CONCLUSION: The excellent performance and usability characteristics
      of INSTI HIV-1/HIV-2 self-test make the kit a viable option for HIV self-testing.
      To improve the identification of weak positive results, the manufacturer should
      indicate on the IFU that even a faint test spot should be interpreted as
      positive.

PMID- 30212526
TI  - Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias.
AB  - PURPOSE: Multiple clinical and epidemiological studies have provided estimates of
      fibromyalgia prevalence and sex ratio, but different criteria sets and
      methodology, as well as bias, have led to widely varying (0.4%->11%) estimates of
      prevalence and female predominance (>90% to <61%). In general, studies have
      failed to distinguish Criteria based fibromyalgia (CritFM) from Clinical
      fibromyalgia (ClinFM). In the current study we compare CritFM with ClinFM to
      investigate gender and other biases in the diagnosis of fibromyalgia. METHODS: We
      used a rheumatic disease databank and 2016 fibromyalgia criteria to study
      prevalence and sex ratios in a selection biased sample of 1761 referred and
      diagnosed fibromyalgia patients and in an unbiased sample of 4342 patients with
      no diagnosis with respect to fibromyalgia. We compared diagnostic and clinical
      variables according to gender, and we reanalyzed a German population study (GPS)
      (n = 2435) using revised 2016 criteria for fibromyalgia. RESULTS: In the
      selection-biased sample of referred patients with fibromyalgia, more than 90%
      were women. However, when an unselected sample of rheumatoid arthritis (RA)
      patients was studied for the presence of fibromyalgia, women represented 58.7% of
      fibromyalgia cases. Women had slightly more symptoms than men, including
      generalized pain (36.8% vs. 32.4%), count of 37 symptoms (4.7 vs. 3.7) and mean
      polysymptomatic distress scores (10.2 vs. 8.2). We also found a linear relation
      between the probability of being females and fibromyalgia and fibromyalgia
      severity. Women in the GPS represented 59.2% of cases. DISCUSSION: The perception
      of fibromyalgia as almost exclusively (>=90%) a women's disorder is not supported
      by data in unbiased studies. Using validated self-report criteria and unbiased
      selection, the female proportion of fibromyalgia cases was <=60% in the unbiased
      studies, and the observed CritFM prevalence of fibromyalgia in the GPS was ~2%.
      ClinFM is the public face of fibromyalgia, but is severely affected by selection
      and confirmation bias in the clinic and publications, underestimating men with
      fibromyalgia and overestimating women. We recommend the use of 2016 fibromyalgia
      criteria for clinical diagnosis and epidemiology because of its updated scoring
      and generalized pain requirement. Fibromyalgia and generalized pain positivity,
      widespread pain (WPI), symptom severity scale (SSS) and polysymptomatic distress
      (PSD) scale should always be reported.

PMID- 30212527
TI  - Antenatal exposure to betamethasone induces placental 11beta-hydroxysteroid
      dehydrogenase type 2 expression and the adult metabolic disorders in mice.
AB  - Antenatal overexposure to glucocorticoids causes fetal intrauterine growth
      restriction (IUGR) and adult metabolic disorders. 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD) 1 and 2 are key enzymes for glucocorticoid metabolism,
      however, the detailed effects of antenatal overexposure to glucocorticoids on
      placental 11beta-HSD1 and 2 expression and adult metabolic disorders remain
      obscure. Here, we report that, in placenta 11beta-HSD1 is diffusely localized,
      whereas 11beta-HSD2 is specifically expressed in labyrinthine layer. Exposure of
      pregnant dams to betamethasone significantly increases the expression of
      placental 11beta-HSD2 but not 11beta-HSD1, and decreases the weights of fetuses
      but not placentas. Antenatal exposure to betamethasone leads to either
      significant weight loss in the offspring younger than 10-week-old, or weight gain
      in those older than 14-week-old. Furthermore, antenatal exposure to betamethasone
      results in coexistence of various metabolic disorders in adult offspring,
      including hyperglycemia, glucose intolerance, low insulin secretory capacity and
      hyperlipidemia. The present study demonstrates that exposure of pregnant dams to
      betamethasone induces the expression of placental 11beta-HSD2 but not 11beta
      HSD1, leads to fetal IUGR and causes adult metabolic disorders, providing
      evidence for fetal origins of adult diseases and the potential role of placental
      11beta-HSD2 in them.

PMID- 30212528
TI  - Surface properties of dental zirconia ceramics affected by ultrasonic scaling and
      low-temperature degradation.
AB  - Zirconia (3Y-TZP) dental prostheses are widely used in clinical dentistry.
      However, the effect of ultrasonic scaling performed as a part of professional
      tooth cleaning on 3Y-TZP dental prostheses, especially in conjunction with low
      temperature degradation (LTD), has not been fully investigated. The present study
      aimed to evaluate the influence of ultrasonic scaling and LTD on the surface
      properties of 3Y-TZP in relation to bacterial adhesion on the treated surface. 3Y
      TZP specimens (4 * 4 * 2 mm) were polished and then subjected to autoclaving at
      134 degrees C for 100 h to induce LTD, followed by 10 rounds of ultrasonic
      scaling using a steel scaler tip for 1 min each. Surface roughness, crystalline
      structure, wettability, and hardness were analyzed by optical interferometry, X
      ray diffraction analysis, contact angle measurement, and nano-indentation
      technique, respectively. Subsequently, bacterial adhesion onto the treated 3Y-TZP
      surface was evaluated using Streptococcus mitis and S. oralis. The results
      demonstrated that the combination of ultrasonic scaling and LTD significantly
      increased the Sa value (surface roughness parameter) of the polished 3Y-TZP
      surface from 1.6 nm to 117 nm. LTD affected the crystalline structure, causing
      phase transformation from the tetragonal to the monoclinic phase, and decreased
      both the contact angle and surface hardness. However, bacterial adhesion was not
      influenced by these changes in surface properties. The present study suggests
      that ultrasonic scaling may be acceptable for debridement of 3Y-TZP dental
      prostheses because it did not facilitate bacterial adhesion even in the
      combination with LTD, although it did cause slight roughening of the surface.

PMID- 30212529
TI  - Anaerobic capacity estimated by the sum of both oxygen equivalents from the
      glycolytic and phosphagen pathways is dependent on exercise mode: Running versus
      cycling.
AB  - The purpose of this study was to verify whether the exercise modality (i.e.,
      running and cycling) alters the magnitude of "anaerobic" capacity estimated by a
      single supramaximal effort (AC[La]+EPOCfast). Fourteen healthy men (age: 26+/-9
      years) underwent a maximum incremental test and a supramaximal effort to
      exhaustion at 115% of the intensity associated with maximal oxygen uptake to
      determine the AC[La]+EPOCfast (i.e., the sum of both oxygen equivalents from the
      glycolytic and phosphagen pathways), performed on both a treadmill and cycle
      ergometer. The maximal oxygen uptake during running was higher (p = 0.001; large
      effect size) vs. cycling (48.9+/-3.9mL.kg-1.min-1 vs. 44.8+/-5.5mL.kg-1.min-1
      respectively). Contrarily, the oxygen equivalent from the glycolytic metabolism
      was not different between exercise modalities (p = 0.133; small effect size;
      running = 2.35+/-0.48 L and cycling = 2.18+/-0.58 L). Furthermore, the
      "anaerobic" capacity was likely meaning fully (3.65+/-0.70 L) and very likely
      meaningfully (949.1+/-5.7 mL.kg-1) greater in running than cycling (3.81+/-0.71 L
      and 52.0+/-8.1 mL.kg-1). Additionally, the contribution of the phosphagen
      metabolism was higher (p = 0.001; large effect size) for running compared to
      cycling (1.6+/-0.3 L vs.1.3+/-0.3 L respectively). Therefore, the "anaerobic"
      capacity estimated by the sum of both oxygen equivalents from the glycolytic and
      phosphagen pathways during a supramaximal effort is influenced by exercise
      modality and is able to identify the difference in phosphagen metabolic
      contribution, based on the methodological conditions of this study.

PMID- 30212530
TI  - The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces
      hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.
AB  - There are no registered veterinary drugs for treating insulin dysregulation and
      preventing insulin-associated laminitis in horses. Velagliflozin is a sodium
      glucose co-transport 2 inhibitor that reduces renal glucose reabsorption,
      promotes glucosuria, and consequently, decreases blood glucose and insulin
      concentrations. This study aimed to determine if velagliflozin reduced
      hyperinsulinemia and prevented laminitis in insulin-dysregulated ponies fed a
      challenge diet high in non-structural carbohydrates (NSC). An oral glucose test
      (1 g dextrose/kg BW) was used to screen 75 ponies for insulin dysregulation, of
      which 49 ponies with the highest insulin concentrations were selected. These
      animals were assigned randomly to either a treated group (n = 12) that received
      velagliflozin (0.3 mg/kg BW, p.o., s.i.d.) throughout the study, or a control
      group (n = 37). All ponies were fed a maintenance diet of alfalfa hay for 3
      weeks, before transferring to a challenge diet (12 g NSC/kg BW/d) for up to 18 d.
      Blood glucose and serum insulin concentrations were measured over 4 h after
      feeding, on d 2 of the diet. The maximum glucose concentration was 22% lower (P =
      0.014) in treated animals, with a geometric mean (95% CI) of 9.4 (8.0-11.0) mM,
      versus 12.1 (10.7-13.7) mM in the controls. This was reflected by lower (45%)
      maximum insulin concentrations in the treated group (P = 0.017), of 149 (97-228)
      MUIU/mL, versus 272 (207-356) MUIU/mL for controls. The diet induced Obel grade 1
      or 2 laminitis in 14 of the 37 controls (38%), whereas no velagliflozin-treated
      pony developed laminitis (P = 0.011). Velagliflozin was well-tolerated, with no
      hypoglycemia or any clinical signs of adverse effects. The main limitation of
      this study was the sample size. Velagliflozin shows promise as a safe and
      effective compound for treating insulin dysregulation and preventing laminitis by
      reducing the hyperinsulinemic response to dietary NSC.

PMID- 30212532
TI  - The feasibility of a training course for clubfoot treatment in Africa: A mixed
      methods study.
AB  - BACKGROUND: There is no available training programme with standard elements for
      health workers treating clubfoot in Africa. Standardised training with continued
      mentorship has the potential to improve management of clubfoot. We aimed to
      evaluate the feasibility of such a training programme among clubfoot providers in
      Africa, and assess implications for training effectiveness and scale up. METHOD:
      We used participatory research with trainers from 18 countries in Africa over two
      years to devise, pilot and refine a 2-day basic and a 2-day advanced clubfoot
      treatment course. (The Africa Clubfoot Training or 'ACT' Course.) The pilots
      involved training 113 participants. Mixed methods (both qualitative and
      quantitative) were used for evaluation. We describe and synthesise the results
      using the eight elements proposed by Bowen et al (2010) to assess feasibility.
      All participants completed feedback questionnaires, and interviews were conducted
      with a subset of participants. We undertook a narrative description of themes
      raised in the participant questionnaires and interviews. Descriptive statistics
      were used to compare pre- and post-course scores for confidence and knowledge.
      RESULTS: 113 participants completed pre and post-course measures (response rate =
      100%). Mean participant confidence increased from 64% (95%CI: 59-69%) to 88%
      (95%CI: 86-91%) post course. Mean participant knowledge increased from 55%
      (95%CI: 51-60%) to 78% (95%CI: 76-81%) post course. No difference was found in
      mean for either subscale of cadre or sex. The qualitative analysis generated
      themes under four domains: 'practical learning in groups', 'interactive
      learning', 'relationship with the trainer' and 'ongoing supervision and
      mentorship'. CONCLUSION: The Africa Clubfoot Training package to teach health
      care workers to manage clubfoot is likely to be feasible in Africa. Future work
      should evaluate its impact on short and long term treatment outcomes and a
      process evaluation of implementation is required.

PMID- 30212531
TI  - Large conductance voltage- and calcium-gated potassium channels (BK) in cerebral
      artery myocytes of perinatal fetal primates share several major characteristics
      with the adult phenotype.
AB  - Large conductance voltage- and calcium-gated channels (BK) control fundamental
      processes, including smooth muscle contractility and artery diameter. We used a
      baboon (Papio spp) model of pregnancy that is similar to that of humans to
      characterize BK channels in the middle cerebral artery and its branches in near
      term (165 dGa) primate fetuses and corresponding pregnant mothers. In cell
      attached patches (K+pipette = 135 mM) on freshly isolated fetal cerebral artery
      myocytes, BK currents were identified by large conductance, and voltage- and
      paxilline-sensitive effects. Their calcium sensitivity was confirmed by a lower
      Vhalf (transmembrane voltage needed to reach half-maximal current) in inside-out
      patches at 30 versus 3 MUM [Ca2+]free. Immunostaining against the BK channel
      forming alpha subunit revealed qualitatively similar levels of BK alpha protein
      corresponding fluorescence in fetal and maternal myocytes. Fetal and maternal BK
      currents recorded at 3 MUM [Ca2+]free from excised membrane patches had similar
      unitary current amplitude, and Vhalf. However, subtle differences between fetal
      and maternal BK channel phenotypes were detected in macroscopic current
      activation kinetics. To assess BK function at the organ level, fetal and maternal
      artery branches were pressurized in vitro at 30 mmHg and probed with the
      selective BK channel blocker paxilline (1 MUM). The degree of paxilline-induced
      constriction was similar in fetal and maternal arteries, yet the constriction of
      maternal arteries was achieved sooner. In conclusion, we present a first
      identification and characterization of fetal cerebral artery BK channels in
      myocytes from primates. Although differences in BK channels between fetal and
      maternal arteries exist, the similarities reported herein advance the idea that
      vascular myocyte BK channels are functional near-term, and thus may serve as
      pharmacological targets during the perinatal-neonatal period.

PMID- 30212533
TI  - Ex vivo drug sensitivity testing as a means for drug repurposing in esophageal
      adenocarcinoma.
AB  - BACKGROUND: Esophageal cancer remains one of the hardest cancers to treat with
      rising incidence rates, low overall survival and high levels of treatment
      resistance. The lack of clinically available biomarkers hinder diagnosis and
      treatment stratification. While large scale sequencing approaches have uncovered
      a number of molecular makers, little has translated in the routine treatment of
      esophageal cancer patients. MATERIAL AND METHODS: We evaluate the treatment
      response towards a panel of 215 FDA-approved and 163 epigenetic compounds of 4
      established and 2 patient-derived esophageal cancer cell lines. Cell viability
      was evaluated after 72h of treatment using cell titer glow. The drug sensitivity
      testing results for gemcitabine and cisplatin were validated using clonogenic
      assays. RESULTS: The tested cell lines display different drug sensitivity
      profiles, although we found compounds that display efficacy in all of the tested
      established or patient-derived cell lines. Clonogenic assays confirmed the
      validity of the drug sensitivity testing results. Using the epigenetic library,
      we observed high sensitivity towards a number of epigenetic modifiers.
      DISCUSSION: Ex vivo drug sensitivity testing may present a viable option for the
      treatment stratification of esophageal cancer patients and holds the potential to
      greatly improve patient outcome while reducing treatment toxicity.

PMID- 30212534
TI  - Olfactory modulation of colour working memory: How does citrus-like smell
      influence the memory of orange colour?
AB  - Olfactory modulation of vision is not well understood whereas visual modulation
      of olfaction has been more fully investigated. This study aimed to reveal in a
      simple manner whether there is olfactory modulation of colour working memory
      using an odour that induces a citrus-like smell and is associated with orange
      colours. We assumed that the odour would have modulatory effects on the colour
      information stored in working memory. To clarify whether these effects are
      supportive or disruptive, during the colour working memory task we measured an
      event-related potential component, P3, which is involved in attentional processes
      of working memory. The results indicated that odour presentation mediated a
      decline in the rate of correct guesses for orange colours. Furthermore, the odour
      suppressed P3 during reddish-colour retrieval, including orange. These results
      suggest that colour working memory in orange can be disrupted via olfactory
      modulation with citrus-like odours.

PMID- 30212535
TI  - Underlying determinants of maternal mortality in a rural South African population
      with high HIV prevalence (2000-2014): A population-based cohort analysis.
AB  - INTRODUCTION: Maternal mortality is one of the significant health indicators of
      any country and it's a frequent subject in many global heath discussions. Even
      though the global trends have shown a decrease on maternal mortality, many
      countries in sub-Saharan Africa failed to achieve the MDG 5 target in 2015.There
      is no specific single solution for reducing maternal mortality but there is
      unanimity that a reliable health system with skilled personal is vital for
      addressing maternal mortality. This study therefore seeks to identify the risk
      factors for maternal mortality in typical rural sub-Saharan African countries.
      METHOD: A longitudinal population based cohort study was conducted using data
      from 2000-2014 in Africa Health Research Institute (AHRI).The Cox regression
      method was used to assess the influence of selected risk factors using the Mosley
      Chen model on maternal mortality. A total of 20701 women aged 15-49 years were
      included in the study. RESULTS: The study found 212 maternal deaths from 32,620
      live births with a maternal mortality ratio (MMR) of 650 per 100,000 live births.
      The main causes of death were Communicable diseases (38.2%), Aids and TB (31%)
      and Unknown causes (11.8%). An increased risk of death was identified on, poor
      wealth index (HR 3.92[1.01, 15.3]), period of death 2000-2006(HR32.1 [3.79,
      71.5]) and number of deliveries (6.76[2.70, 16.9]) were associated with a high
      risk of maternal mortality after adjusting for other independent variables
      included in the study. CONCLUSION: Socio-economic status, number of deliveries
      and period of death were found to be associated with maternal death in rural
      South Africa.

PMID- 30212536
TI  - Study on the aggregation behavior of kaolinite particles in the presence of
      cationic, anionic and non-ionic surfactants.
AB  - Aggregation behaviors of kaolinite particles with different surfactants were
      studied in this paper. Aggregation settling yield and fractal dimension analysis
      were used to determine the aggregation results. Zeta potential measurements,
      adsorption tests, Infrared spectroscopy analysis and scanning electron microscope
      measurements were conducted for further investigation into the mechanism.
      Experimental results showed that much better aggregation results was obtained in
      the presence of cationic surfactant than that in the presence of anionic and non
      ionic surfactants. 98% aggregation setting yield was obtained in the presence of
      dodecylamine. Adsorption tests indicated that the adsorption capacity of
      dodecylamine on kaolinite surface was larger than that of sodium oleate and
      Tween80. Zeta potential measurements confirmed that dodecylamine was more
      beneficial to the aggregation of kaolinite particles. Infrared spectroscopy
      analysis revealed that the adsorption of dodecylamine on kaolinite surface was
      attributed to electrostatic and hydrogen-bonding interactions. Sodium oleate was
      adsorbed by chemical adsorption. However, Tween80 can hardly be adsorbed by
      kaolinite surface.

PMID- 30212537
TI  - CD4+T cells mediate protection against Zika associated severe disease in a mouse
      model of infection.
AB  - Zika virus (ZIKV) has gained worldwide attention since it emerged, and a global
      effort is underway to understand the correlates of protection and develop
      diagnostics to identify rates of infection. As new therapeutics and vaccine
      approaches are evaluated in clinical trials, additional effort is focused on
      identifying the adaptive immune correlates of protection against ZIKV disease. To
      aid in this endeavor we have begun to dissect the role of CD4+T cells in the
      protection against neuroinvasive ZIKV disease. We have identified an important
      role for CD4+T cells in protection, demonstrating that in the absence of CD4+T
      cells mice have more severe neurological sequela and significant increases in
      viral titers in the central nervous system (CNS). The transfer of CD4+T cells
      from ZIKV immune mice protect type I interferon receptor deficient animals from a
      lethal challenge; showing that the CD4+T cell response is necessary and
      sufficient for control of ZIKV disease. Using a peptide library spanning the
      complete ZIKV polyprotein, we identified both ZIKV-encoded CD4+T cell epitopes
      that initiate immune responses, and ZIKV specific CD4+T cell receptors that
      recognize these epitopes. Within the ZIKV antigen-specific TCRbeta repertoire, we
      uncovered a high degree of diversity both in response to a single epitope and
      among different mice responding to a CD4+T cell epitope. Overall this study
      identifies a novel role for polyfunctional and polyclonal CD4+T cells in
      providing protection against ZIKV infection and highlights the need for vaccines
      to develop robust CD4+T cell responses to prevent ZIKV neuroinvasion and limit
      replication within the CNS.

PMID- 30212538
TI  - Chronic kidney disease (CKD) patients are exposed to more proton pump inhibitor
      (PPI)s compared to non-CKD patients.
AB  - BACKGROUND: Proton pump inhibitor use is associated with incident chronic kidney
      disease, chronic kidney disease progression and end-stage renal disease. However,
      the extent of proton pump inhibitor prescriptions to chronic kidney disease
      patients is still unclear. METHOD: In a retrospective study, we enrolled patients
      (>18 years old) who received proton pump inhibitor in the out-patient setting
      from 2014 through 2015. All data was obtained from electronical medical records
      of Soonchunhyang Medical Center. The prescription patterns and characteristics of
      proton pump inhibitors were analyzed according to individual estimated glomerular
      filtration rate of the patients. RESULT: During the study period 178,228 patients
      visited the out-patient clinic. Proton pump inhibitors were prescribed to 9,109
      (5.11%) patients. In our sample, 50% were females and 9.8% were chronic kidney
      disease (eGFR<60mL/min/1.73 m2) patients. Among the patients with chronic kidney
      disease, 730 (8.0%) were categorized as stage 3 or 4 and 166 (1.8%) were
      categorized as stage 5 or end-stage renal disease. The prevalence of proton pump
      inhibitors prescription among chronic kidney disease patients was higher than in
      the non-chronic kidney disease group (p<0.001). Median duration of usage was 120
      [interquartile range 63-273] days in the stage 3-4 group, 106 [56-266] days in
      the stage 5-end-stage renal disease group and 90 [56-176] days in the non-chronic
      kidney disease group. Patients in stage 3-4 group were prescribed longer duration
      of proton pump inhibitors than the non-chronic kidney disease group even after
      adjusting for age and sex (p<0.001). The main departments of medicine which
      prescribed proton pump inhibitors for the stage 3-4 group were gastroenterology
      (40.0%), cardiology (29.6%), nephrology (9.5%) and neurology (4.8%). Compared to
      the non-chronic kidney disease group, the stage 3-4 and stage 5-end-stage renal
      disease group were taking larger number of drugs simultaneously (6.90+/-4.17
      vs4.54+/-2.43; p<0.001, 5.64+/-2.87 vs 4.54+/-2.34; p<0.001, respectively).
      CONCLUSION: Chronic kidney disease patients are taking proton pump inhibitors for
      a much longer duration compared to non-chronic kidney disease patients.
      Physicians should pay careful attention when prescribing proton pump inhibitors
      to high risk groups.

PMID- 30212539
TI  - Psychometric evaluation of the Family Focused Mental Health Practice
      Questionnaire in measuring home visitors' family focused practice.
AB  - BACKGROUND: Worldwide maternal mental illness poses a major public health issue.
      Supporting maternal mental health and family health is a core aspect of home
      visiting. Increasingly the benefits of family focused treatments to maternal
      mental illness are being recognised. However, there are few reliable and valid
      measures that attempt to assess this type of practice. OBJECTIVES: To explore the
      psychometric properties of the Family Focused Mental Health Practice
      Questionnaire in a population of home visitors. METHODS: Home visitors (n = 230)
      from across a single region of the United Kingdom completed the Family Focused
      Mental Health Practice Questionnaire. Participants were all females, had a mean
      age of 44 years, and had an average of 11 years' experience of home visiting.
      Exploratory factor analysis was used to explore the factor structure of the
      questionnaire in this population while Cronbach's alpha was used to assess the
      internal consistency of questionnaire subscales. RESULTS: Exploratory factor
      analysis revealed a 3-factor solution where each factor contained at least three
      questionnaire items and had eigenvalues >= 1.0. Checks for internal consistency
      revealed that one factor was unsatisfactory (alpha < 0.6), which was subsequently
      discarded. A further exploratory factor analysis supported a 2 factor solution.
      The factors were named: professional influences on family focused practice and
      organisational influences on family focused practice. Cronbach's alpha for the
      new scale was 0.949. CONCLUSION: As home visitors play a key role in supporting
      parents who have mental illness and their families, it is important to assess
      their practice using a reliable measure. Our psychometric evaluation has created
      a more valid, reliable and concise measure that can be used to examine home
      visitors' family focused practice.

PMID- 30212540
TI  - Biomarkers for diagnosis of childhood tuberculosis: A systematic review.
AB  - INTRODUCTION: As studies of biomarkers of tuberculosis (TB) disease provide hope
      for a simple, point-of-care test, we aimed to synthesize evidence on biomarkers
      for diagnosis of TB in children and compare their accuracy to published target
      product profiles (TPP). METHODS: We conducted a systematic review of biomarkers
      for diagnosis of pulmonary TB in exclusively paediatric populations, defined as
      age less than 15 years. PubMed, EMBASE and Web of Science were searched for
      relevant publications from January 1, 2000 to November 27, 2017. Studies using
      mixed adult and paediatric populations or reporting biomarkers for extrapulmonary
      TB were excluded. Study quality was assessed using the Quality Assessment of
      Diagnostic Accuracy Studies-2 (QUADAS-2) framework. No meta-analysis was done
      because the published childhood TB biomarkers studies were mostly early stage
      studies and highly heterogeneous. RESULTS: The 29 studies included in this
      systematic review comprise 20 case-control studies, six cohort studies and three
      cross-sectional studies. These studies reported diverse and heterogeneous forms
      of biomarkers requiring different types of clinical specimen and laboratory
      assays. Majority of the studies (27/29 [93%]) either did not meet the criteria in
      at least one of the four domains of the QUADAS-2 reporting framework or the
      assessment was unclear. However, the diagnostic performance of biomarkers
      reported in 22 studies met one or both of the WHO-recommended minimal targets of
      66% sensitivity and 98% specificity for a new diagnostic test for TB disease in
      children, and/or 90% sensitivity and 70% specificity for a triage test.
      CONCLUSION: We found that majority of the biomarkers for diagnosis of TB in
      children are promising but will need further refining and optimization to improve
      their performances. As new data are emerging, stronger emphasis should be placed
      on improving the design, quality and general reporting of future studies
      investigating TB biomarkers in children.

PMID- 30212541
TI  - Turning off the empathy switch: Lower empathic concern for the victim leads to
      utilitarian choices of action.
AB  - Empathy enables people to vicariously experience the other's pain. At the same
      time, the focus of empathy can be narrow and reserved for a limited number of
      people. In sacrificial dilemmas, non-empathic people are more likely to sacrifice
      one person for greater good. However, no study has investigated the role of
      diminished empathic concern for the victim in utilitarian choices of action. In
      two studies, we investigated how empathy actually experienced in sacrificial
      dilemmas affects a decision to perform a harmful action onto the victim. In Study
      1 (N = 275), participants were asked to rate the extent to which they were
      feeling two divergent tropes of affective empathy: other-oriented empathy
      (empathic concern) and self-oriented empathy (personal distress). Results showed
      that lower levels of other-focused empathy for the victim predicted utilitarian
      choices of action. In Study 2 (N = 170), participants were asked to rate the
      extent to which they empathized with the victim and the saved. We also assessed
      dispositional empathy and psychopathy to test a hypothesis that psychopathy
      mediates the relationship between lower empathy for the victim and utilitarian
      choices of action. Results supported this hypothesis, whereas dispositional
      empathy was not significantly correlated with utilitarian choices of action.
      Overall, lower empathy experienced in the dilemma situation was associated with
      utilitarian choices of action, and this was specific to reduced empathic concern
      for the victim. People choose to pursue the utilitarian end that accompanies harm
      onto the other as a mean when the victim is out of their empathic focus.

PMID- 30212542
TI  - Food and water restriction lead to differential learning behaviors in a head
      fixed two-choice visual discrimination task for mice.
AB  - Head-fixed behavioral tasks can provide important insights into cognitive
      processes in rodents. Despite the widespread use of this experimental approach,
      there is only limited knowledge of how differences in task parameters, such as
      motivational incentives, affect overall task performance. Here, we provide a
      detailed methodological description of the setup and procedures for training mice
      efficiently on a two-choice lick left/lick right visual discrimination task. We
      characterize the effects of two distinct restriction regimens, i.e. food and
      water restriction, on animal wellbeing, activity patterns, task acquisition, and
      performance. While we observed reduced behavioral activity during the period of
      food and water restriction, the average animal discomfort scores remained in the
      'sub-threshold' and 'mild' categories throughout the experiment, irrespective of
      the restriction regimen. We found that the type of restriction significantly
      influenced specific aspects of task acquisition and engagement, i.e. the number
      of sessions until the learning criterion was reached and the number of trials
      performed per session, but it did not affect maximum learning curve performance.
      These results indicate that the choice of restriction paradigm does not strongly
      affect animal wellbeing, but it can have a significant effect on how mice perform
      in a task.

PMID- 30212543
TI  - Enabling tomography with low-cost C-arm systems.
AB  - In scenarios where the use of a Computed Tomography (CT) is difficult, such as
      during surgery or in the ICU, the use of a C-arm system to generate tomographic
      information could contribute with interesting additional clinical information.
      Recent days are seeing the development of the so-called cone-beam CT (CBCT) based
      on advanced motorized isocentric C-arm systems. To be able to make use of more
      basic C-arm systems, apart from the geometric non-idealities common to any CBCT,
      we need to address other difficulties. First, the trajectory of the source
      detector pair may differ from a circular path and the system may suffer
      mechanical strains that modify the relative positions of the source and detector
      for different projection angles. Second, and more importantly, the exact position
      of the source and detector elements may not be repeatable for consecutive
      rotations due to low mechanical precision, thus preventing an accurate
      geometrical calibration of the system. Finally, the limitation of the angular
      span and the difficulty of obtaining a high number of projections pose a great
      challenge to the image reconstruction. In this work, we present a novel method to
      adapt a standard C-arm, originally designed for planar imaging, to be used as a
      tomograph. The key parts of the new acquisition protocol are (1) a geometrical
      calibration method to compensate mechanical inaccuracies that prevent an accurate
      repetition of source-detector position between acquisitions, and (2) an advanced
      image reconstruction method able to deal with limited angle data, sparse
      projections and non-circular trajectories. Both methods exploit surface
      information from the patient, which can be obtained using a 3D surface scanner.
      The proposed method was evaluated with two real C-arm systems, based on an image
      intensifier and a flat panel detector respectively, showing the feasibility of
      the proposal.

PMID- 30212544
TI  - Improvement of reverse sequence algorithm for syphilis diagnosis using optimal
      treponemal screening assay signal-to-cutoff ratio.
AB  - BACKGROUND: Although reverse sequence algorithms (RSA) for syphilis screening are
      performing well, they still have to rely on treponemal confirmatory tests at
      least for sera reactive by enzyme immunoassay/chemiluminescence immunoassay
      (EIA/CIA) and unreactive by rapid plasma reagin (RPR). Quebec's laboratory
      network previously showed that 3.3% of EIA/CIA reactive and weakly-reactive RPR
      samples (RPR titer of 1 to 4) would have been misclassified as syphilis cases if
      a treponemal confirmatory test had not been performed. OBJECTIVES: To correlate
      the magnitude of signal-to-cutoff (S/CO) ratios of the 4 most used commercial
      first-line EIA/CIA kits in Quebec with syphilis confirmation results and
      establish a S/CO value above which treponemal confirmation would not be required.
      METHODS: Serum samples from previously undiagnosed individuals (n = 7 404)
      obtained between January 2014 and February 2017 that were reactive by EIA/CIA and
      either negative by RPR or reactive with a low titer (1 to 4) were included in the
      study. All samples were tested with Treponema pallidum particle agglutination (TP
      PA) and, if negative or inconclusive, with a line immunoassay (LIA). Syphilis
      infection confirmation was defined by a reactive TP-PA or LIA. Logistic
      regression analysis was used to determine S/CO values (95% CI lower bound = 0.98)
      above which confirmation would not be required. The four kits studied were
      Architect TP, BioPlex IgG, Syphilis EIA II, and Trep-Sure. RESULTS: Of 2609
      reactive EIA/CIA specimens tested for the determination of S/CO values, 1730
      (66%) were confirmed as true syphilis cases. Confirmation rate was significantly
      higher in samples with low-titer positive RPR (92%) than with negative RPR
      samples (54%); p<0.01. A linear probability model (95% CI lower bound = 0.98)
      predicted the S/CO value above which a confirmation would no longer be needed for
      the Architect TP (16.4), Bioplex IgG (7.4) and Trep-Sure (24.6). No linearity was
      observed between the S/CO value of Syphilis EIA II and the confirmation rate. The
      validity of the predicted S/CO values was investigated using 4 795 specimens. The
      use of an S/CO value of 16.4 with the Architect TP kit and of 24.6 for the Trep
      Sure kit would obviate the need for confirmation of 18.5% and 13.2% of sera from
      the all RPR subgroup, respectively. For the BioPlex IgG kit, 81.1% of sera would
      not require confirmation when using the S/CO value of 7.4 in the low titer RPR
      subgroup. CONCLUSION: Signal-to-cut-off values could be used to identify sera
      that do not require extra treponemal confirmation for 3 of the 4 most used first
      line EIA/CIA kits in Quebec. Using these values in our current reverse screening
      algorithm (RSA) would avoid the need for confirmatory tests in 14 to 20% of sera,
      a proportion that could reach 75% among low-titer RPR.

PMID- 30212545
TI  - Effect of pupil dilation on biometric measurements and intraocular lens power
      calculations in schoolchildren.
AB  - PURPOSE: To investigate the effect of pupil dilation on ocular biometric
      parameters and intraocular lens (IOL) power calculation in schoolchildren using
      the Lenstar LS 900. METHODS: One hundred forty eyes of 140 healthy schoolchildren
      were included in the analysis. Axial length (AL), central corneal thickness
      (CCT), aqueous depth (AD), anterior chamber depth (ACD), lens thickness (LT),
      flat keratometry (K), steep K, astigmatism, white-to-white (WTW), and iris/pupil
      barycenter distance were measured, before and after pupil dilation. Anterior
      segment length (ASL) was defined as the sum of ACD and LT, and lens position (LP)
      was defined as ACD plus half of the LT. The relative lens position (RLP) was
      defined as LP divided by AL. IOL power was calculated using the eight formulas
      (Hill-RBF, Barrett, Haigis, Hoffer Q, Holladay, Olsen, SRK II, and SRK/T)
      integrated in the Lenstar LS 900. Parameters before and after pupil dilation were
      compared. RESULTS: AL, AD, ACD, LT, ASL, LP, RLP, flat K, iris barycenter
      distance, pupil barycenter distance, and PD differed significantly after pupil
      dilation (P < 0.001 in all cases), as compared to before dilation. The Olsen
      formula demonstrated significant differences in the magnitude of astigmatism (P =
      0.010) and IOL power (P = 0.003) after pupil dilation. Using the different
      formulas, 23.6-40.7% of participants had IOL power changes of more than 0.50
      diopters, while 0.7-1.4% had IOL changes of more than 1.0 diopter after pupil
      dilation. CONCLUSIONS: Dilated and undilated pupil size affected the Lenstar LS
      900 measurement of some ocular biometric parameters, and pupil dilation led to
      IOL power changes exceeding 0.50 diopters with a high percentage (from 23.6% to
      40.7%) in schoolchildren, which should be noticed in clinical practice.

PMID- 30212546
TI  - Natural variations in the promoter of OsSWEET13 and OsSWEET14 expand the range of
      resistance against Xanthomonas oryzae pv. oryzae.
AB  - Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the
      major diseases that impact rice production in Asia. The bacteria use
      transcription activator-like effectors (TALEs) to hijack the host transcription
      machinery and activate key susceptibility (S) genes, specifically members of the
      SWEET sucrose uniporters through the recognition of effector-binding element
      (EBEs) in the promoter regions. However, natural variations in the EBEs that
      alter the binding affinity of TALEs usually prevent sufficient induction of SWEET
      genes, leading to resistance phenotypes. In this study, we identified candidate
      resistance alleles by mining a rice diversity panel for mutations in the promoter
      of OsSWEET13 and OsSWEET14, which are direct targets of three major TALEs PthXo2,
      PthXo3 and AvrXa7. We found natural variations at the EBE of both genes, which
      appeared to have emerged independently in at least three rice subspecies. For
      OsSWEET13, a 2-bp deletion at the 5th and 6th positions of the EBE, and a
      substitution at the 17th position appear to be sufficient to prevent activation
      by PthXo2. Similarly, a single nucleotide substitution at position 10 compromised
      the induction of OsSWEET14 by AvrXa7. These findings might increase our
      opportunities to reduce pathogen virulence by preventing the induction of SWEET
      transporters. Pyramiding variants along with other resistance genes may provide
      durable and broad-spectrum resistance to the disease.

PMID- 30212547
TI  - Knowledge and use of HIV pre-exposure prophylaxis among men who have sex with men
      in Berlin - A multicentre, cross-sectional survey.
AB  - BACKGROUND: HIV pre-exposure prophylaxis (PrEP) has likely contributed to large
      decreases in HIV incidence among men who have sex with men (MSM) in several major
      cities. Berlin has seen a smaller decline, and affordable PrEP has been
      accessible through formal channels in Germany only since autumn 2017. We aimed to
      investigate knowledge and use of PrEP among MSM in Berlin, and factors predictive
      of a desire to use PrEP and history of PrEP use. METHODS: Multicentre, paper
      based, self-administered survey of adult MSM whose HIV status was negative or
      unknown at time of participation. Data were collected from 1 October 2017 to 2
      April 2018. RESULTS: 473 of 875 questionnaires were returned (response rate
      54.1%; mean age 37.4 years, range 18-79). 90.0% of participants were aware of
      PrEP and, of these, 48.2% felt well informed about it. Among the 17.2% of
      participants reporting PrEP use, 59.3% indicated obtaining some or all of it from
      informal sources. 23.7% of those with no history of PrEP use reported having
      condomless anal intercourse (CAI) with two or more partners over the past six
      months. Worries about side effects, cost, not having a doctor who prescribes it,
      and a lack of information were the most frequently reported barriers to PrEP use.
      A desire to use PrEP and history of PrEP use were associated in our multivariable
      model with having multiple CAI partners. A history of PrEP use was associated
      with having a university degree, one or two parents born outside Germany, or
      friends living with HIV. CONCLUSIONS: We found high awareness of PrEP among MSM
      in Berlin, but also a strong need for more education on its pros, cons and proper
      use. The frequency of informal PrEP use was also high, raising urgent individual
      and public health concerns. Policy makers need to consider recent calls to
      improve access to PrEP and PrEP education through regular health services.

PMID- 30212548
TI  - Evolutionary history and spatiotemporal dynamics of the HIV-1 subtype B epidemic
      in Guatemala.
AB  - Different explanations exist on how HIV-1 subtype B spread in Central America,
      but the role of Guatemala, the Central American country with the highest number
      of people living with the virus, in this scenario is unknown. We investigated the
      evolutionary history and spatiotemporal dynamics of HIV-1 subtype B in Guatemala.
      A total of 1,047 HIV-1 subtype B pol sequences, from newly diagnosed ART-naive,
      HIV-infected Guatemalan subjects enrolled between 2011 and 2013 were combined
      with published subtype B sequences from other Central American countries (n =
      2,101) and with reference sequences representative of the BPANDEMIC and BCAR
      lineages from the United States (n = 465), France (n = 344) and the Caribbean (n
      = 238). Estimates of evolutionary, demographic, and phylogeographic parameters
      were obtained from sequence data using maximum likelihood and Bayesian coalescent
      based methods. The majority of Guatemalan sequences (98.9%) belonged to the
      BPANDEMIC clade, and 75.2% of these sequences branched within 10 monophyletic
      clades: four also included sequences from other Central American countries (BCAM
      I to BCAM-IV) and six were mostly (>99%) composed by Guatemalan sequences (BGU
      clades). Most clades mainly comprised sequences from heterosexual individuals.
      Bayesian coalescent-based analyses suggested that BGU clades originated during
      the 1990s and 2000s, whereas BCAM clades originated between the late 1970s and
      mid 1980s. The major hub of dissemination of all BGU, and of BCAM-II, and BCAM-IV
      clades was traced to the Department of Guatemala, while the root location of BCAM
      I and BCAM-III was traced to Honduras. Most Guatemalan clades experienced initial
      phases of exponential growth (0.23 and 3.6 year-1), followed by recent growth
      declines. Our observations suggest that the Guatemalan HIV-1 subtype B epidemic
      is driven by dissemination of multiple BPANDEMIC founder viral strains, some
      restricted to Guatemala and others widely disseminated in the Central American
      region, with Guatemala City identified as a major hub of viral dissemination. Our
      results also suggest the existence of different sub-epidemics within Guatemala
      for which different targeted prevention efforts might be needed.

PMID- 30212549
TI  - Food and nutrient gaps in rural Northern Ghana: Does production of smallholder
      farming households support adoption of food-based dietary guidelines?
AB  - Food-based dietary guidelines (FBDGs) provide guidance to policy makers, the
      private sector and consumers to redesign food systems and to improve diets of
      vulnerable populations. As appropriate FBDGs are based on the actual dietary
      patterns and their costs, it is assumed that the recommended foods are available,
      affordable and acceptable for the population under study. Using quantitative
      dietary intake data of young children in rural Northern Ghana, we developed local
      FBDGs and studied whether these are supported by the diversity and quantity of
      the production of a household among 329 households. We found that 40% of rural
      Northern Ghanaian infants and young children were stunted and their nutrient
      intakes were far below the recommendations: the probability of adequacy for most
      nutrient intakes was less than 50%. At household level, the developed FBDGs were,
      on average, unable to sufficiently cover the household requirements for fat
      (60.4% of recommended nutrient intake (RNI)), calcium (34.3% RNI), iron (60.3%
      RNI), vitamin A (39.1% RNI), vitamin B12 (2.3% RNI) and vitamin C (54.6% RNI).
      This implies that even when these FBDGs are fully adopted the requirements for
      these nutrients will not be met. In addition, the nutrient needs and food needs
      (according to the developed FBDGs) of a household were only marginally covered by
      their own food production. The food production of over half the households
      supplied insufficient calcium (75.7%), vitamin A (100%), vitamin B12 (100%) and
      vitamin C (77.5%) to cover their needs. The food production of about 60% of the
      households did not cover their required quantities of grains and legumes and none
      covered their required quantities of vegetables. Further analysis of the food
      gaps at district and national level showed that sufficient grains were available
      at both levels (267% and 148%, respectively) to meet requirements; availability
      of legumes was sufficient at district level (268%) but not at national level
      (52%); and vegetables were insufficient at both levels (2% and 49%,
      respectively). Diversifying household food production is often proposed as a
      means to increase the diversity of foods available and thereby increasing dietary
      diversity of rural populations. We found that the diversity of the production of
      a household was indeed positively related with their food and nutrient coverage.
      However, the diversity of the production of a household and their food and
      nutrient coverage were not related with children's dietary diversity and nutrient
      adequacy. Our results show that the production of a households does not support
      the adoption of FBDGs in rural Northern Ghana, especially for vegetables. This
      suggests that the promotion of FBDGs through nutrition education or behaviour
      change communications activities alone is insufficient to lead to improvements in
      diets. Additional strategies are needed to increase the food availability and
      accessibility of the households, especially that of fruits and vegetables, such
      as diversification of the crops grown, increased production of specific crops and
      market-based strategies.

PMID- 30212550
TI  - Interdevice variability of central corneal thickness measurement.
AB  - PURPOSE: To evaluate variability of central corneal thickness measurement (CCT)
      devices using a hitherto unprecedented number of CCT devices. METHODS: CCT was
      measured consecutively in 122 normal corneas of 61 subjects with seven different
      devices using three distinct measurement technologies: Scheimpflug, Ultrasound,
      and Optical Coherence Tomography (OCT). Per device deviation from the mean CCT
      value per eye was used to determine which of the devices performed best, compared
      to the mean value. RESULTS: Cirrus OCT yielded the lowest deviation. Deviations
      of the individual devices from the mean CCT of each eye were (OS/OD) 12.8+/
      5.0/14.9+/-9.4 MUm for Topcon noncontact specular microscopy (NCSM), 11.3+/
      5.9/10.6+/-7.3 MUm for Pentacam, 10.7+/-5.2/10.4+/-4.8 MUm for Spectralis OCT,
      6.0+/-3.9/6.2+/-4.9 MUm for Topcon DRI OCT, 5.1+/-3.4/5.9+/-10.3 MUm for AngioVue
      OCT, 4.8+/-4.1/5.7+/-4.6 MUm for US pachymetry, and 4.2+/-3.2/5.7+/-4.6 MUm for
      Cirrus OCT. The maximum differences between US pachymetry and the other devices
      were very high (up to 120 MUm). CONCLUSION: Central corneal thickness may be
      under- or overestimated due to high interdevice variations. Measuring CCT with
      one device only may lead to inappropriate clinical and surgical recommendations.
      OCT showed superior results.

PMID- 30212551
TI  - Characterization of a novel disease-associated mutation within NPHS1 and its
      effects on nephrin phosphorylation and signaling.
AB  - Mutations in the transmembrane protein nephrin (encoded by NPHS1) underlie nearly
      half of all cases of congenital nephrotic syndrome (CNS), which is caused by
      aberrations in the blood filtering function of glomerular podocytes. Nephrin
      directly contributes to the structure of the filtration barrier, and it also
      serves as a signaling scaffold in podocytes, undergoing tyrosine phosphorylation
      on its cytoplasmic tail to recruit intracellular effector proteins. Nephrin
      phosphorylation is lost in several human and experimental models of glomerular
      disease, and genetic studies have confirmed its importance in maintenance of the
      filtration barrier. To date, however, the effect of CNS-associated NPHS1 variants
      on nephrin phosphorylation remains to be determined, which hampers genotype
      phenotype correlations. Here, we have characterized a novel nephrin sequence
      variant, A419T, which is expressed along with C623F in a patient presenting with
      CNS. Nephrin localization is altered in kidney biopsies, and we further
      demonstrate reduced surface expression and ER retention of A419T and C623F in
      cultured cells. Moreover, we show that both mutations impair nephrin tyrosine
      phosphorylation, and they exert dominant negative effects on wildtype nephrin
      signaling. Our findings thus reveal that missense mutations in the nephrin
      extracellular region can impact nephrin signaling, and they uncover a potential
      pathomechanism to explain the spectrum of clinical severity seen with mild NPHS1
      mutations.

PMID- 30212553
TI  - The symmetry of the Kepler problem, the inverse Ligon-Schaaf mapping and the
      Birkhoff conjecture.
AB  - The Ligon-Schaaf regularization (LS mapping) was introduced in 1976 and has been
      used several times. However, we are not aware of any direct usage of the inverse
      mapping, perhaps since it appears at first sight to be quite complex, involves
      the use of a transcendental equation (referred to as the generalized Kepler
      equation) that cannot be solved in closed form, and lacks smoothness near the
      collision point. Here, we provide some insight into the significance of this
      equation, along with a very simple derivation and confirmation of the inverse LS
      mapping. Then we use numerical methods to investigate three applications: 1)
      solutions of the Kepler function, 2) calculation of orbits including time-of
      flight data based on the Delaunay Hamiltonian, and 3) numerical evidence for the
      Birkhoff conjecture for the circular restricted 3-body problem.

PMID- 30212552
TI  - Alterations in heart rate variability in patients with peripheral arterial
      disease requiring surgical revascularization have limited association with
      postoperative major adverse cardiovascular and cerebrovascular events.
AB  - OBJECTIVE: Obstructive sleep apnea (OSA) is common in peripheral arterial disease
      (PAD) and associates with high mortality after surgery. Since abnormal heart rate
      variability (HRV) is predictive of postoperative complications, we investigated
      the relations of HRV with PAD, OSA and major adverse cardiovascular and
      cerebrovascular events (MACCE). MATERIALS AND METHODS: Seventy-five patients
      (67+/-9 years) scheduled for sub-inguinal revascularization and 15 controls (63+/
      6 years) underwent polysomnography and HRV analyses. OSA with an apnea-hypopnea
      index (AHI) >=20/hour was considered significant. HRV was measured during
      wakefulness, S2, S3-4 and rapid eye movement (REM) sleep with time and frequency
      domain methods including beat-to-beat variability, low frequency (LF) and high
      frequency (HF) power, and detrended fluctuation analysis (DFA). MACCE was defined
      as cardiac death, myocardial infarction, coronary revascularization, hospitalized
      angina pectoris and stroke. RESULTS: Thirty-six patients (48%) had AHI>=20/hour.
      During follow-up (median 52 months), 22 patients (29%) suffered a MACCE. Compared
      to controls, fractal correlation of HRV (scaling exponent alpha 1 measured with
      DFA) was weaker during S2 and evening wakefulness in all subgroups (+/
      AHI>=20/hour, +/-MACCE) but only in patients with AHI>=20/hour during morning
      wakefulness. The LF/HF ratio was lower in all subgroups during S2 but only in
      patients with AHI >=20/hour during evening or morning wake. In the covariance
      analysis adjusted for age, body mass index, coronary artery disease and PAD
      duration, the alpha 1 during morning wakefulness remained significantly lower in
      patients with AHI>=20/hour than in those without (1.12 vs. 1.45; p = 0.03).
      Decreased HF during REM (p = 0.04) and S3-4 sleep (p = 0.03) were predictive of
      MACCE. In analyses with all sleep stages combined, mean heart rate as well as
      very low frequency, LF, HF and total power were associated with OSA of mild-to
      moderate severity (AHI 10-20/hour). CONCLUSIONS: HRV is altered in patients with
      PAD. These alterations have a limited association with OSA and MACCE.

PMID- 30212554
TI  - Genetic insights into elephantgrass persistence for bioenergy purpose.
AB  - Persistence may be defined as high sustained yield over multi-harvest. Genetic
      insights about persistence are essential to ensure the success of breeding
      programs and any biomass-based project. This paper focuses on assessing the
      biomass yield persistence for bioenergy purpose of 100 elephantgrass clones
      measured in six growth seasons in Brazil. To assess the clones' persistence, an
      index based on random regression models and genotype-ideotype distance was
      proposed. Results suggested the existence of wide genetic variability between
      elephantgrass clones, and that the yield trajectories along the harvests generate
      genetic insights into elephantgrass clones' persistence and G x E interaction. A
      gene pool that acts over the biomass yield (regardless of the harvest) was
      detected, as well as other gene pools, which show differences on genes expression
      (these genes are the major responsible for clones' persistence). The lower and
      higher clones' persistence was discussed based on genome dosage effect and
      natural biological nitrogen fixation ability applied to bioenergy industry. The
      huge potential of energy crops necessarily is associated with genetic insights
      into persistence, so just this way, breeding programs could breed a new cultivar
      that fulfills the bioenergy industries.

PMID- 30212555
TI  - Alternative package leaflets improve people's understanding of drug side effects
      A randomized controlled exploratory survey.
AB  - BACKGROUND: Current German and EU package leaflets (PLs) do not distinguish to
      what extent listed side effects are indeed side effects caused by drug intake or
      instead symptoms that occur regardless of drug use. We recently showed that most
      health professionals misinterpret the frequencies of listed side effects as
      solely caused by the drug. The present study investigated whether (1) these
      misinterpretations also prevail among laypeople and (2) alternative PLs reduce
      these misinterpretations. METHODS: In March 2017, 397 out of 400 laypeople
      approached completed an online survey. They were randomized to one of four PL
      formats: three alternative PLs (drug facts box with/without reading instruction,
      narrative format with numbers) and one standard PL. Each PL listed four side
      effects for a fictitious drug: two were presented as occurring more often, one as
      equally often, and one as less often with drug intake. The alternative formats
      (interventions) included information on frequencies with and without drug intake
      and included a statement on the causal relation. The standard PL (control) only
      included information on frequency ranges with drug intake. Questions were asked
      on general occurrence and causality of side effects. RESULTS: Participants
      randomized to the standard PL were unable to answer questions on causality. For
      side effects occurring more often (equally; less often) with drug intake, only
      1.9% to 2.8% (equally: 1.9%; less often: 1.9%) provided correct responses about
      the causal nature of side effects, compared to 55.0% to 81.9% (equally: 23.8% to
      70.5%; less often: 21.0% to 43.2%) of participants who received alternative PLs.
      It remains unclear whether one alternative format is superior to the others.
      CONCLUSION: In conclusion, information on the frequency of side effects in
      current package leaflets is misleading. Comparative presentation of frequencies
      for side effects with and without drug intake including statements on the causal
      relation significantly improves understanding.

PMID- 30212556
TI  - Study on healing technique for weak interlayer and related mechanical properties
      based on microbially-induced calcium carbonate precipitation.
AB  - The weak interlayer refers to the filling material in shear belts or large-scale
      structural planes, which is usually composed of soil, fine sand and gravels. It
      is prone to argillization when encountering water and its mechanical strength and
      stiffness are generally low, which has adverse effects on the stability of
      underground structures. In recent years, research on reinforcement techniques for
      weak interlayers has been a hot topic in geotechnical field. As a new
      reinforcement method for structural planes, the microbial healing technique has
      attracted a lot of attention. In this paper, a study on the healing technique for
      weak interlayer based on microbially induced calcium carbonate precipitation
      (MICP) and related mechanical properties was conducted for the interlayer shear
      belt at Baihetan Hydropower Station in China. First, Sporosarcina pasteurii was
      activated in laboratory. Reinforcement of the weak interlayer was realized by
      utilizing calcium carbonate precipitation on the weak interlayer. Continuous
      monitoring of the precipitates on the weak interlayer by XRD and SEM indicated
      that the precipitates on the weak layer were microbially induced calcium
      carbonate. Its crystals were irregular fish scale-shaped cubes with size in the
      range of 5~20MUm. With favorable crystal growth, the crystals and the particles
      of the weak interlayer were cemented together. Finally, the mechanical properties
      of the healed weak interlayer were tested and the variations of uniaxial
      compressive strength, shear strength and triaxial compressive strength with
      bacteria concentration were discussed. The test results indicated that the
      maximum uniaxial compressive strength, peak shear strength and triaxial
      compressive strength can be increased by 149%, 162% and 119%, respectively, which
      subsequently improve the overall strength of the shear zone or structural plane.
      This can provide a new idea for soft ground reinforcement in underground
      projects.

PMID- 30212557
TI  - Optimization of the Cohesion Index in the SeDeM Diagram Expert System and
      application of SeDeM Diagram: An improved methodology to determine the Cohesion
      Index.
AB  - In this study, we suggest optimizing the methodology to determine the Cohesion
      Index (Icd) in order to avoid mistaken characterizations due to powder bulk
      density. For this purpose, five different excipients, with different bulk
      densities and of different chemical nature, were compressed at different heights.
      Their compression and their tablet characterization enable establishing a powder
      weight for compression in accordance with its bulk density. Therefore, the
      resulting tablet will have a height within a defined range of heights where it
      has no critical effects on its hardness. Then, the impact of this optimization is
      shown in a formula development, one of the main SeDeM's applications. A
      mathematical equation was used to calculate the theoretical amount of excipient
      to formulate the API according to both methodologies. The compression results
      demonstrate that the characterization with the NM-Icd is more accurate than the
      previous one while preserving its simplicity.

PMID- 30212558
TI  - Differentiation in fitness-related traits in response to elevated temperatures
      between leading and trailing edge populations of marine macrophytes.
AB  - The nature of species distribution boundaries is a key subject in ecology and
      evolution. Edge populations are potentially more exposed to climate-related
      environmental pressures. Despite research efforts, little is known about
      variability in fitness-related traits in leading (i.e., colder, high latitude)
      versus trailing (i.e., warmer, low latitude) edge populations. We tested whether
      the resilience, i.e. the resistance and recovery, of key traits differs between a
      distributional cold (Greenland) and warm (Portugal) range edge population of two
      foundation marine macrophytes, the intertidal macroalga Fucus vesiculosus and the
      subtidal seagrass Zostera marina. The resistance and recovery of edge populations
      to elevated seawater temperatures was compared under common experimental
      conditions using photosynthetic efficiency and expression of heat shock proteins
      (HSP). Cold and warm edge populations differed in their response, but this was
      species specific. The warm edge population of F. vesiculosus showed higher
      thermal resistance and recovery whereas the cold leading edge was less tolerant.
      The opposite was observed in Z. marina, with reduced recovery at the warm edge,
      while the cold edge was not markedly affected by warming. Our results confirm
      that differentiation of thermal stress responses can occur between leading and
      trailing edges, but such responses depend on local population traits and are thus
      not predictable just based on thermal pressures.

PMID- 30212559
TI  - Factors affecting soil microbial biomass and functional diversity with the
      application of organic amendments in three contrasting cropland soils during a
      field experiment.
AB  - The effects of soil type and organic material quality on the microbial biomass
      and functional diversity of cropland soils were studied in a transplant
      experiment in the same climate during a 1-year field experiment. Six organic
      materials (WS: wheat straw, CS: corn straw, WR: wheat root, CR: corn root, PM:
      pig manure, CM: cattle manure), and three contrasting soils (Ferralic Cambisol,
      Calcaric Cambisol and Luvic Phaeozem) were chosen. At two time points (at the end
      of the 1st and 12th months), soil microbial biomass carbon (C) and nitrogen (N)
      (MBC and MBN) and Biolog Ecoplate substrate use patterns were determined, and the
      average well color development and the microbial functional diversity indices
      (Shannon, Simpson and McIntosh indices) were calculated. Organic material quality
      explained 29.5-50.9% of the variance in MBC and MBN when compared with the minor
      role of soil type (1.4-9.3%) at the end of the 1st and 12th months, and C/N ratio
      and total N of organic material were the main parameters. Soil properties, e.g.,
      organic C and clay content were the predominant influence on microbial functional
      diversity in particular at the end of the 12th month (61.8-82.8% of the variance
      explained). The treatments of WS and CS significantly improved the MBC and
      microbial functional diversity indices over the control in the three soils in
      both sampling periods (P < 0.05). These results suggest that the application of
      crop straw is a long-term effective measure to increase microbial biomass, and
      can further induce the changes of soil properties to regulate soil microbial
      community.

PMID- 30212560
TI  - Newborn blood DNA epigenetic variations and signaling pathway genes associated
      with Tetralogy of Fallot (TOF).
AB  - Tetralogy of Fallot (TOF) is the most common Critical Congenital Heart Defect
      (CCHD). The etiology of TOF is unknown in most cases. Preliminary data from our
      group and others suggest that epigenetic changes may play an important role in
      CHD. Epidemiologically, a significant percentage of CHD including TOF fail to be
      diagnosed in the prenatal and early newborn period which can negatively affect
      health outcomes. We performed genome-wide methylation assay in newborn blood in
      24 non-syndromic TOF cases and 24 unaffected matched controls using Illumina
      Infinium HumanMethylation450 BeadChips. We identified 64 significantly
      differentially methylated CpG sites in TOF cases, of which 25 CpG sites had high
      predictive accuracy for TOF, based on the area under the receiver operating
      characteristics curve (AUC ROC) >= 0.90). The CpG methylation difference between
      TOF and controls was >=10% in 51 CpG targets suggesting biological significance.
      Gene ontology analysis identified significant biological processes and functions
      related to these differentially methylated genes, including: CHD development,
      cardiomyopathy, diabetes, immunological, inflammation and other plausible
      pathways in CHD development. Multiple genes known or plausibly linked to heart
      development and post-natal heart disease were found to be differentially
      methylated in the blood DNA of newborns with TOF including: ABCB1, PPP2R5C, TLR1,
      SELL, SCN3A, CREM, RUNX and LHX9. We generated novel and highly accurate putative
      molecular markers for TOF detection using leucocyte DNA and thus provided
      information on pathogenesis of TOF.

PMID- 30212561
TI  - High rates of sexual violence by both intimate and non-intimate partners
      experienced by adolescent girls and young women in Kenya and Zambia: Findings
      around violence and other negative health outcomes.
AB  - BACKGROUND: While links between intimate-partner violence (IPV) and HIV risk have
      been established, less is known about violence perpetrated by people other than
      intimate partners. In addition, much of the research on IPV has been conducted
      with adults, while relatively little is known about violence experienced by
      adolescent girls and young women (AGYW). We examined experiences of sexual
      violence and associated sexual and mental health among AGYW in Kenya and Zambia.
      METHODS: Using cross-sectional surveys with women aged 15-24 years, we assessed
      experience of partner sexual violence among respondents who reported a
      boyfriend/husband in the last 12 months (Kenya N = 597; Zambia N = 426) and non
      partner sexual violence among all respondents (Kenya N = 1778; Zambia N = 1915).
      We conducted logistic regression analyses to examine experiences of sexual
      violence and health outcomes. RESULTS: Sexual violence from intimate partners
      over the last year was reported by 19.1 percent of AGYW respondents in Kenya and
      22.2 percent in Zambia; sexual violence from non-partners was reported by 21.4
      percent in Kenya and 16.9 percent in Zambia. Experience of sexual violence was
      associated with negative health outcomes. Violence from non-partners was
      associated with increased odds of STI symptoms and increased levels of anxiety
      and depression. Results were similar for violence from partners, although only
      significant in Kenya. While sexual violence from a non-partner was associated
      with increased HIV risk perception, it was not associated when the violence was
      experienced from an intimate partner. CONCLUSIONS: AGYW reported high levels of
      sexual violence from both intimate partners and non-partners. These experiences
      were associated with negative health outcomes, though there were some differences
      by country context. Strengthening sexual violence prevention programs, increasing
      sexual violence screening, and expanding the provision of post-violence care are
      needed to reduce intimate and non-partner violence and the effects of violence on
      AGYW.

PMID- 30212562
TI  - Stroke incidence and anticoagulation treatment in patients with pacemaker
      detected silent atrial fibrillation.
AB  - BACKGROUND: Silent atrial fibrillation (AF) episodes are common but the role of
      anticoagulation treatment is under debate. METHODS: Consecutive patients with
      dual-chamber pacemakers for sinus node disease or AV block/bundle branch block
      were retrospectively enrolled and the development of silent AF, any
      anticoagulation and the incidence of ischaemic stroke and dementia were recorded.
      RESULTS: In total 411 patients without and 267 with known AF at implant were
      included. During a median follow-up of 38 months, 30% (125/411) of patients
      without known AF at implant were diagnosed with silent AF, 62% of those had or
      were prescribed anticoagulation. Heart failure (p = 0.03) and age >75 years (p =
      0.0002) were risk markers for incident silent AF. In patients with known AF at
      implant, 80% (216/267) were on anticoagulation at implant. The annual stroke
      incidence was 2.1% in patients with known AF at implant, as compared to 1.9% in
      patients who developed silent AF during follow-up, and 1.4% in patients without
      AF. Vascular dementia developed in 11.2% and 6.2% respectively in patients with
      known AF versus no AF (p = 0.048) as well as in 5.6% of those with silent AF (p =
      0.09). CONCLUSION: The stroke risk in our study population with an incident
      silent AF diagnosis may have been significantly decreased by the high proportion
      of anticoagulation treatment. This could imply that without this treatment the
      stroke risk might have been high enough to justify anticoagulation. Development
      of vascular dementia was twice as common among patients with known AF as compared
      to those witht silent AF or no AF. More data is needed to inform the optimal
      treatment for these patients.

PMID- 30212564
TI  - Association between emergency physician self-reported empathy and patient
      satisfaction.
AB  - BACKGROUND: Higher physician self-reported empathy has been associated with
      higher overall patient satisfaction. However, more evidence-based research is
      needed to determine such association in an emergent care setting. OBJECTIVE: To
      evaluate the association between physician self-reported empathy and after-care
      instant patient-to-provider satisfaction among Emergency Department (ED)
      healthcare providers with varying years of medical practice experience. RESEARCH
      DESIGN: A prospective observational study conducted in a tertiary care hospital
      ED. METHODS: Forty-one providers interacted with 1,308 patients across 1,572
      encounters from July 1 through October 31, 2016. The Jefferson Scale of Empathy
      (JSE) was used to assess provider empathy. An after-care instant patient
      satisfaction survey, with questionnaires regarding patient-to-provider
      satisfaction specifically, was conducted prior to the patient moving out of the
      ED. The relation between physician empathy and patient satisfaction was estimated
      using risk ratios (RR) and their corresponding 95% confidence limits (CL) from
      log-binomial regression models. RESULTS: Emergency Medicine (EM) residents had
      the lowest JSE scores (median 111; interquartile range [IQR]: 107-122) and senior
      physicians had the highest scores (median 119.5; IQR: 111-129). Similarly, EM
      residents had the lowest percentage of "very satisfied" responses (65%) and
      senior physicians had the highest reported percentage of "very satisfied"
      responses (69%). There was a modest positive association between JSE and
      satisfaction (RR = 1.04; 95% CL: 1.00, 1.07). CONCLUSION: This study provides
      evidence of a positive association between ED provider self-reported empathy and
      after-care instant patient-to-provider satisfaction. Overall higher empathy
      scores were associated with higher patient satisfaction, though minor
      heterogeneity occurred between different provider characteristics.

PMID- 30212563
TI  - Encoding of locomotion kinematics in the mouse cerebellum.
AB  - The cerebellum is involved in coordinating motor behaviour, but how the
      cerebellar network regulates locomotion is still not well understood. We
      characterised the activity of putative cerebellar Purkinje cells, Golgi cells and
      mossy fibres in awake mice engaged in an active locomotion task, using high
      density silicon electrode arrays. Analysis of the activity of over 300 neurons in
      response to locomotion revealed that the majority of cells (53%) were
      significantly modulated by phase of the stepping cycle. However, in contrast to
      studies involving passive locomotion on a treadmill, we found that a high
      proportion of cells (45%) were tuned to the speed of locomotion, and 19% were
      tuned to yaw movements. The activity of neurons in the cerebellar vermis provided
      more information about future speed of locomotion than about past or present
      speed, suggesting a motor, rather than purely sensory, role. We were able to
      accurately decode the speed of locomotion with a simple linear algorithm, with
      only a relatively small number of well-chosen cells needed, irrespective of cell
      class. Our observations suggest that behavioural state modulates cerebellar
      sensorimotor integration, and advocate a role for the cerebellar vermis in
      control of high-level locomotor kinematic parameters such as speed and yaw.

PMID- 30212565
TI  - Peripapillary and macular choroidal area in patients with normal-tension
      glaucoma.
AB  - PURPOSE: To evaluate normal and normal-tension glaucoma (NTG) eyes for
      differences in peripapillary and macular choroidal area measurements. METHODS:
      This cross-sectional comparative study enrolled 52 normal subjects and 35 NTG
      patients. Peripapillary and macular choroidal images were recorded by enhanced
      depth imaging optical coherence tomography (EDI-OCT), with conversion of the
      luminal and interstitial areas to binary images performed using the Niblack
      method. RESULTS: While there was a significant difference between normal subjects
      and NTG patients for the peripapillary choroidal area (1,853,672 +/- 626,501 MUm2
      vs. 1,606,448 +/- 418,214 MUm2, P = 0.047), there were no significant differences
      between the normal subjects and NTG patients observed for the macular choroidal
      area (345,365 +/- 119,248 MUm2 vs. 316,442 +/- 85,732 MUm2, P = 0.23). In the NTG
      patients, multivariate regression analysis demonstrated a correlation between the
      macular choroidal area and the axial length (beta = -0.345, P = 0.04).
      Furthermore, there was also a significant correlation between the peripapillary
      choroidal area and the age of the NTG patients (beta = -0.469, P = 0.004). In
      addition, there was no relationship between the glaucoma severity and the
      peripapillary and macular choroidal areas in the NTG patients. CONCLUSIONS: There
      was no correlation between the peripapillary choroidal area and glaucoma severity
      in NTG patients, even though the area was smaller in these patients.

PMID- 30212566
TI  - Enzymatic chokepoints and synergistic drug targets in the sterol biosynthesis
      pathway of Naegleria fowleri.
AB  - Naegleria fowleri is a free-living amoeba that can also act as an opportunistic
      pathogen causing severe brain infection, primary amebic meningoencephalitis
      (PAM), in humans. The high mortality rate of PAM (exceeding 97%) is attributed to
      (i) delayed diagnosis, (ii) lack of safe and effective anti-N. fowleri drugs, and
      (iii) difficulty of delivering drugs to the brain. Our work addresses
      identification of new molecular targets that may link anti-Naegleria drug
      discovery to the existing pharmacopeia of brain-penetrant drugs. Using inhibitors
      with known mechanism of action as molecular probes, we mapped the sterol
      biosynthesis pathway of N. fowleri by GC-MS analysis of metabolites. Based on
      this analysis, we chemically validated two enzymes downstream to CYP51, sterol
      C24-methyltransferase (SMT, ERG6) and sterol Delta8-Delta7 -isomerase (ERG2), as
      potential therapeutic drug targets in N. fowleri. The sterol biosynthetic cascade
      in N. fowleri displayed a mixture of canonical features peculiar to different
      domains of life: lower eukaryotes, plants and vertebrates. In addition to the
      cycloartenol->ergosterol biosynthetic route, a route leading to de novo
      cholesterol biosynthesis emerged. Isotopic labeling of the de novo-synthesized
      sterols by feeding N. gruberi trophozoites on the U13C-glucose-containing growth
      medium identified an exogenous origin of cholesterol, while 7-dehydrocholesterol
      (7DHC) had enriched 13C-content, suggesting a dual origin of this metabolite both
      from de novo biosynthesis and metabolism of scavenged cholesterol. Sterol
      homeostasis in Naegleria may be orchestrated over the course of its life-cycle by
      a "switch" between ergosterol and cholesterol biosynthesis. By demonstrating the
      growth inhibition and synergistic effects of the sterol biosynthesis inhibitors,
      we validated new, potentially druggable, molecular targets in N. fowleri. The
      similarity of the Naegleria sterol Delta8-Delta7 -isomerase to the human non
      opioid sigma1 receptor, implicated in human CNS conditions such as addiction,
      amnesia, pain and depression, provides an incentive to assess structurally
      diverse small-molecule brain-penetrant drugs targeting the human receptor for
      anti-Naegleria activity.

PMID- 30212567
TI  - 320-row CT transcatheter aortic valve replacement planning with a single reduced
      contrast media bolus injection.
AB  - OBJECTIVE: To reduce the iodine load required for CT Transcatheter Aortic Valve
      Replacement (TAVR) planning on a 320-row scanner by acquiring the two CT TAVR
      steps (ECG-gated aortic root CTA and non-gated aorto-ilio-femoral CTA) within a
      single contrast media bolus injection. METHODS: 50 consecutive patients (82.6+/
      6.9 years; 56% female) were prospectively enrolled and underwent a TAVR planning
      using a 320-row CT, with ECG-gated aortic root CTA immediately followed by a non
      gated aorto-iliac acquisition, all within a single bolus of 40-70mL of Iohexol
      350mgI/mL. The Iodine load, image quality, SNR, CNR and radiation dose were
      compared using a Mann-Whitney test to that of 24 consecutive patients (84.3+/-4.8
      years, 58% female) previously imaged on a 64-row scanner with a conventional two
      step protocol. RESULTS: Iodine load was reduced by 44%. All examinations were of
      diagnostic quality, with improvement of the aortic root CTA image quality (4.9+/
      0.3 versus 4.6+/-0.5, p<0.01) and a non-significant decrease of the aorto-iliac
      CTA image quality (4.7+/-0.6 versus 4.9+/-0.3, p = 0.07). SNR and CNR were
      significantly improved in the aortic root CTA (14.0+/-5.3 and 10.4+/-4.5 versus
      10.3+/-4.2 and 6.8+/-3.3, p<0.01 for both) and non-significantly higher in the
      aorto-iliac CTA (16.5+/-8.0 and 14.1+/-7.9 versus 14.7+/-5.5 and 12.5+/-5.0, p =
      0.42 and p = 0.66). Total radiation dose was reduced by 32%. CONCLUSION: 320-row
      CT scanner enables a 44% reduction of iodine load in TAVR planning, while
      maintaining excellent aorto-ilio-femoral arterial enhancement and lowering
      radiation dose.

PMID- 30212568
TI  - Shugoshin 1 is dislocated by KSHV-encoded LANA inducing aneuploidy.
AB  - Shugoshin-1 (Sgo1) protects the integrity of the centromeres, and H2A
      phosphorylation is critical for this process. The mitotic checkpoint kinase Bub1,
      phosphorylates H2A and ensures fidelity of chromosome segregation and chromosome
      number. Oncogenic KSHV induces genetic alterations through chromosomal
      instability (CIN), and its essential antigen LANA regulates Bub1. We show that
      LANA inhibits Bub1 phosphorylation of H2A and Cdc20, important for chromosome
      segregation and mitotic signaling. Inhibition of H2A phosphorylation at residue
      T120 by LANA resulted in dislocation of Sgo1, and cohesin from the centromeres.
      Arrest of Cdc20 phosphorylation also rescued degradation of Securin and Cyclin B1
      at mitotic exit, and interaction of H2A, and Cdc20 with Bub1 was inhibited by
      LANA. The N-terminal nuclear localization sequence domain of LANA was essential
      for LANA and Bub1 interaction, reversed LANA inhibited phosphorylation of H2A and
      Cdc20, and attenuated LANA-induced aneuploidy and cell proliferation. This
      molecular mechanism whereby KSHV-induced CIN, demonstrated that the NNLS of LANA
      is a promising target for development of anti-viral therapies targeting KSHV
      associated cancers.

PMID- 30212569
TI  - Outbreaks of histoplasmosis: The spores set sail.

PMID- 30212571
TI  - Relationship between the dissemination of small ruminant lentivirus infection in
      goat herds and opinion of farmers on the occurrence of arthritis.
AB  - Small ruminant lentivirus (SRLV) infection manifests itself mainly with chronic
      progressive arthritis affecting mainly carpal joints. The data from serological
      and questionnaire surveys were retrospectively analyzed to determine how the
      dissemination of SRLV infection in the herd influenced farmer's subjective
      opinion on the occurrence of swelling of carpal joints (considered as a proxy of
      arthritis). Between 1996 and 2017 153 different Polish dairy goat herds counting
      at least 20 adult goats were serologically screened for CAE and their owners were
      asked about their opinion on the occurrence of arthritis (never, rarely, often).
      Of them 73 SRLV-seropositive herds, in which true seroprevalence had been
      estimated, were included in the analysis. The ordinal logistic regression model
      was developed to determine the relationship between the true within-herd
      seroprevalence and the probability that the farmer would observe arthritis in the
      herd never, rarely or often. True within-herd seroprevalence ranged from 0.2% to
      100% with the median of 34.6%. Farmers declared not to have observed arthritis in
      40 (54.8%) herds, to have seen it rarely in 9 (12.3%) of herds, and to have
      observed it often in 24 (32.9%) of herds. The model proved that the probability
      of observing goats with carpal arthritis in the herd was significantly linked to
      the true within-herd seroprevalence (OR = 1.058, CI 95% from 1.037 to 1.078;
      p<0.001), but this relationship was not linear and SRLV infection proved to
      remain unapparent to farmers even when a considerable part of the herd had
      already become infected. Concluding, the study shows that when the farmer
      realizes that goats in the herd suffer from arthritis, SRLV infection is almost
      certainly already widespread in the herd.

PMID- 30212570
TI  - The MAPK kinase BcMkk1 suppresses oxalic acid biosynthesis via impeding
      phosphorylation of BcRim15 by BcSch9 in Botrytis cinerea.
AB  - The mitogen-activated protein kinase (MAPK) cassette of the cell wall integrity
      (CWI) pathway is primarily responsible for orchestrating changes of cell wall.
      However, functions of this cassette in other cellular processes are not well
      understood. Here, we found that the Botrytis cinerea mutant of MAPK kinase
      (BcMkk1) displays more serious defects in mycelial growth, conidiation, responses
      to cell wall and oxidative stresses, but possesses less reduced virulence than
      the mutants of its upstream (BcBck1) and downstream (BcBmp3) kinases.
      Interestingly, BcMkk1, but not BcBck1 and BcBmp3, negatively regulates production
      of oxalic acid (OA) and activity of extracellular hydrolases (EHs) that are
      proposed to be virulence factors of B. cinerea. Moreover, we obtained evidence
      that BcMkk1 negatively controls OA production via impeding phosphorylation of the
      Per-Arnt-Sim (PAS) kinase BcRim15 by the Ser/Thr kinase BcSch9. In addition, the
      fungal Pro40 homolog BcPro40 was found to interact simultaneously with three
      MAPKs, implying that BcPro40 is a scaffold protein of the CWI pathway in B.
      cinerea. Taken together, results of this study reveal that BcMkk1 negatively
      modulates virulence via suppressing OA biosynthesis in B. cinerea, which provides
      novel insight into conserved and species-specific functions of the MAPK kinase in
      fungi.

PMID- 30212572
TI  - Plant A20/AN1 protein serves as the important hub to mediate antiviral immunity.
AB  - Salicylic acid (SA) is a key phytohormone that mediates a broad spectrum of
      resistance against a diverse range of viruses; however, the downstream pathway of
      SA governed antiviral immune response remains largely to be explored. Here, we
      identified an orchid protein containing A20 and AN1 zinc finger domains,
      designated Pha13. Pha13 is up-regulated upon virus infection, and the transgenic
      monocot orchid and dicot Arabidopsis overexpressing orchid Pha13 conferred
      greater resistance to different viruses. In addition, our data showed that
      Arabidopsis homolog of Pha13, AtSAP5, is also involved in virus resistance. Pha13
      and AtSAP5 are early induced by exogenous SA treatment, and participate in the
      expression of SA-mediated immune responsive genes, including the master regulator
      gene of plant immunity, NPR1, as well as NPR1-independent virus defense genes. SA
      also induced the proteasome degradation of Pha13. Functional domain analysis
      revealed that AN1 domain of Pha13 is involved in expression of orchid NPR1
      through its AN1 domain, whereas dual A20/AN1 domains orchestrated the overall
      virus resistance. Subcellular localization analysis suggested that Pha13 can be
      found localized in the nucleus. Self-ubiquitination assay revealed that Pha13
      confer E3 ligase activity, and the main E3 ligase activity was mapped to the A20
      domain. Identification of Pha13 interacting proteins and substrate by yeast two
      hybrid screening revealed mainly ubiquitin proteins. Further detailed biochemical
      analysis revealed that A20 domain of Pha13 binds to various polyubiquitin chains,
      suggesting that Pha13 may interact with multiple ubiquitinated proteins. Our
      findings revealed that Pha13 serves as an important regulatory hub in plant
      antiviral immunity, and uncover a delicate mode of immune regulation through the
      coordination of A20 and/or AN1 domains, as well as through the modulation of E3
      ligase and ubiquitin chain binding activity of Pha13.

PMID- 30212573
TI  - Real-time, simultaneous myoelectric control using a convolutional neural network.
AB  - The evolution of deep learning techniques has been transformative as they have
      allowed complex mappings to be trained between control inputs and outputs without
      the need for feature engineering. In this work, a myoelectric control system
      based on convolutional neural networks (CNN) is proposed as a possible
      alternative to traditional approaches that rely on specifically designed
      features. This CNN-based system is validated using a real-time Fitts' law style
      target acquisition test requiring single and combined wrist motions. The
      performance of the proposed system is then compared to that of a standard support
      vector machine (SVM) based myoelectric system using a set of time-domain
      features. Despite the prevalence and demonstrated performance of these well-known
      features, no significant difference (p>0.05) was found between the two methods
      for any of the computed control metrics. This demonstrates the potential for
      automated learning approaches to extract complex and rich information from
      stochastic biological signals. This first evaluation of the usability of a CNN in
      a real-time myoelectric control environment provides a basis for further
      exploration.

PMID- 30212574
TI  - Food cue-induced craving in individuals with bulimia nervosa and binge-eating
      disorder.
AB  - Individuals with bulimia nervosa (BN) or binge-eating disorder (BED) experience
      more frequent and intense food cravings than individuals without binge eating.
      However, it is currently unclear whether they also show larger food cue-induced
      increases in craving (i.e., food cue reactivity) than those without binge eating,
      as suggested by conditioning theories of binge eating. A group of individuals
      with BN or BED (binge-eating group, n = 27) and a group of individuals with low
      trait food craving scores and without binge eating (control group, n = 19)
      reported their current food craving before and after a food cue exposure.
      Although food craving intensity significantly increased in both groups, this
      increase was significantly stronger in the binge-eating group than in the control
      group. This result is in line with conditioning models of binge eating that
      propose that food cues are conditioned stimuli that elicit a conditioned response
      (e.g., food craving) and that this association is stronger in individuals with
      binge eating. As food craving increased in individuals with low trait food
      craving scores as well-although to a lesser extent-previous null results might be
      explained by methodological considerations such as not screening control
      participants for trait food craving.

PMID- 30212575
TI  - Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium
      term chemically-induced male and female models.
AB  - Hepatocellular carcinoma causes ~10% of all cancer-related deaths worldwide,
      usually emerging in a background of liver fibrosis/cirrhosis (70%-90% of cases).
      Chemically-induced mouse models for fibrosis-associated hepatocarcinogenesis are
      widely-applied, resembling the corresponding human disease. Nonetheless, a long
      time is necessary for the development of preneoplastic/neoplastic lesions. Thus,
      we proposed an early fibrosis-associated hepatocarcinogenesis model for male and
      female mice separately, focusing on reducing the experimental time for
      preneoplastic/neoplastic lesions development and establishing standard models for
      both sexes. Then, two-week old susceptible C3H/HeJ male and female mice (n = 8
      animals/sex/group) received a single dose of diethylnitrosamine (DEN, 10 or 50
      mg/Kg). During 2 months, mice received 3 weekly doses of carbon tetrachloride
      (CCl4, 10% corn oil solution, 0.25 to 1.50 MUL/g b.wt.) and they were euthanized
      at week 17. DEN/CCl4 protocols for males and females displayed clear liver
      fibrosis, featuring collagen accumulation and hepatic stellate cell activation
      (alpha-SMA). In addition, liver from males displayed increased CD68+ macrophage
      number, COX-2 protein expression and IL-6 levels. The DEN/CCl4 models in both
      sexes impaired antioxidant defense as well as enhanced hepatocyte proliferation
      and apoptosis. Moreover, DEN/CCl4-treated male and female developed multiple
      preneoplastic altered hepatocyte foci and hepatocellular adenomas. As expected,
      the models showed clear male bias. Therefore, we established standard and
      suitable fibrosis-associated hepatocarcinogenesis models for male and female
      mice, shortening the experimental time for the development of hepatocellular
      preneoplastic/neoplastic lesions in comparison to other classical models.

PMID- 30212576
TI  - Surgical results of internal limiting membrane flap inversion and internal
      limiting membrane peeling for macular hole.
AB  - PURPOSE: The internal limiting membrane (ILM) is a normal part of the retina, and
      the outcomes of ILM removal have not been fully investigated. ILM flap inversion
      is a recently developed technique that increases the success rate of macular hole
      (MH) surgery. Thus, we compared the anatomical closure rate and visual outcome in
      patients undergoing microincision vitrectomy surgery (MIVS) with ILM flap
      inversion or conventional ILM peeling for the treatment of MH. METHODS: The
      medical records of 90 eyes with MH were reviewed retrospectively. The patients
      were classified into two groups based on MIVS procedure (group 1: ILM flap
      inversion, 46 eyes; group 2: ILM peeling, 44 eyes). RESULTS: Preoperative
      characteristics were similar in the two groups, and there were no significant
      differences in 1 month- or 6 month-postoperative VA between the groups (P = 0.25
      and P = 0.42, respectively). However, the surgical success rate was significantly
      higher in group 1 than group 2 (P = 0.04; 46/46: 100% and 41/44: 93%,
      respectively). Multiple regression analysis revealed that axial length and MH
      diameter were independent factors predicting 6-month postoperative BCVA in group
      2 (P = 0.001 and P = 0.03, respectively), and that MH diameter was an independent
      factor predicting 6-month postoperative VA in group 1 (P = 0.03). Logistic
      regression analysis revealed that axial length (OR = 2.11; P = 0.02; area under
      the curve: 0.94; cut off score: 28.4 mm) was an independent factor indicating
      surgical failure in group 2. CONCLUSION: Our results suggest that MIVS with ILM
      flap inversion might be best suited to treat MH, particularly in patients with
      high myopia.

PMID- 30212577
TI  - Pancreatic duct size and gland texture are associated with pancreatic fistula
      after pancreaticoduodenectomy but not after distal pancreatectomy.
AB  - BACKGROUND: Pancreatic fistula remains a morbid complication after
      pancreatectomy. Since the proposed mechanism of pancreatic fistula is different
      between pancreaticoduodenectomy and distal pancreatectomy, we hypothesized that
      pancreatic gland texture and duct size are not associated with pancreatic fistula
      after distal pancreatectomy. METHODS: All patients >=18 years in the 2014-15
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP) targeted pancreatectomy dataset were linked with the ACS NSQIP Public Use
      File (PUF). Pancreatic duct size (<3 mm, 3-6 mm, >6 mm) and pancreatic gland
      texture (hard, intermediate, soft) were categorized. Separate multivariable
      analyses were performed to evaluate associations between pancreatic duct size and
      gland texture after pancreaticoduodenectomy and distal pancreatectomy. RESULTS: A
      total of 9366 patients underwent pancreaticoduodenectomy or distal pancreatectomy
      during the study period. Proportion of pancreatic fistula was similar after
      distal pancreatectomy (606 of 3132, 19.4%) and pancreaticoduodenectomy (1163 of
      6335, 18.4%, p = 0.245). Both pancreatic gland texture and duct size were
      significantly associated with pancreatic fistula after pancreaticoduodenectomy
      (p<0.001). However, there was no association between pancreatic fistula and gland
      texture or duct size (all p>=0.169) after distal pancreatectomy. Operative
      approach (minimally invasive versus open) was not associated with pancreatic
      fistula after distal pancreatectomy (p = 0.626). Patients with pancreatic fistula
      after distal pancreatectomy had increased rate of postoperative complications
      including longer length of stay, higher rates of readmission and reoperation
      compared to patients who did not have a pancreatic fistula (all p<0.001).
      CONCLUSIONS: Unlike among patients who had pancreaticoduodenectomy, pancreatic
      gland texture and duct size are not associated with development of pancreatic
      fistula following distal pancreatectomy. Other clinical factors should be
      considered in this patient population.

PMID- 30212578
TI  - Machinability investigation in turning of high density fiberboard.
AB  - A series of experiments were conducted to assess the machinability of high
      density fiberboard using cemented carbide cutting tools. The objective of this
      work was to investigate the influence of two cutting parameters, spindle speed
      and feed per turn, on cutting forces, chip formation and cutting quality. The
      results are as follows: cutting forces and chip-breaking length decrease with
      increasing spindle speed and decreasing feed per turn. In contrast, surface
      roughness increases with decrease of spindle speed and increase in feed per turn.
      Chips were divided into four categories based on their shape: dust, particle,
      splinter, and semicontinuous chips. Chip-breaking length had a similar tendency
      to the variance of cutting forces with respect to average roughness and mean peak
      to-valley height: an increase in the variance of cutting forces resulted in
      increased average roughness and mean peak-to-valley height. Thus, high cutting
      speed and low feed rate are parameters suitable for high-quality HDF processing
      and will improve not only machining quality, but production efficiency.

PMID- 30212579
TI  - Great phenotypic and genetic variation among successive chronic Pseudomonas
      aeruginosa from a cystic fibrosis patient.
AB  - BACKGROUND/OBJECTIVES: Different adapted Pseudomonas aeruginosa morphotypes are
      found during chronic infections. Relevant biological determinants in P.
      aeruginosa successively isolated from a cystic fibrosis (CF) patient were
      analyzed in this work to gain insight into P. aeruginosa heterogeneity during
      chronic infection. METHODS: Seventeen P. aeruginosa isolates collected from a
      patient over a 3 year period were included, 5 small colony variants (SCV) and 12
      mucoids. The following analyses were performed: Pulsed-Field-Gel-Electrophoresis
      (PFGE)/Multilocus- sequence-typing (MLST)/serotype, antimicrobial susceptibility,
      growth curves, capacity to form biofilm, pigment production, elastase activity,
      motility; presence/expression of virulence/quorum sensing genes, and
      identification of resistance mechanisms. RESULTS: All isolates had closely
      related PFGE patterns and belonged to ST412. Important phenotypic and genotypic
      differences were found. SCVs were more resistant to antimicrobials than mucoid
      isolates. AmpC hyperproduction and efflux pump activity were detected. Seven
      isolates contained two integrons and nine isolates only one integron. All SCVs
      showed the same OprD profile, while three different profiles were identified
      among mucoids. No amino acid changes were found in MutL and MutS. All isolates
      were slow-growing, generally produced high biofilm, had reduced their toxin
      expression and their quorum sensing, and showed low motility. Nevertheless,
      statistically significant differences were found among SCV and mucoid isolates.
      SCVs grew faster, presented higher biofilm formation and flicA expression; but
      produced less pyorubin and pyocyanin, showed lower elastase activity and rhlR,
      algD, and lasB expression than mucoid isolates. CONCLUSION: These results help to
      understand the molecular behavior of chronic P. aeruginosa isolates in CF
      patients.

PMID- 30212580
TI  - The Arctic charr (Salvelinus alpinus) genome and transcriptome assembly.
AB  - Arctic charr have a circumpolar distribution, persevere under extreme
      environmental conditions, and reach ages unknown to most other salmonids. The
      Salvelinus genus is primarily composed of species with genomes that are
      structured more like the ancestral salmonid genome than most Oncorhynchus and
      Salmo species of sister genera. It is thought that this aspect of the genome may
      be important for local adaptation (due to increased recombination) and anadromy
      (the migration of fish from saltwater to freshwater). In this study, we describe
      the generation of a new genetic map, the sequencing and assembly of the Arctic
      charr genome (GenBank accession: GCF_002910315.2) using the newly created genetic
      map and a previous genetic map, and present several analyses of the Arctic charr
      genes and genome assembly. The newly generated genetic map consists of 8,574
      unique genetic markers and is similar to previous genetic maps with the exception
      of three major structural differences. The N50, identified BUSCOs, repetitive DNA
      content, and total size of the Arctic charr assembled genome are all comparable
      to other assembled salmonid genomes. An analysis to identify orthologous genes
      revealed that a large number of orthologs could be identified between salmonids
      and many appear to have highly conserved gene expression profiles between
      species. Comparing orthologous gene expression profiles may give us a better
      insight into which genes are more likely to influence species specific
      phenotypes.

PMID- 30212582
TI  - Correction: Improvement in cardiac dysfunction with a novel circuit training
      method combining simultaneous aerobic-resistance exercises. A randomized trial.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0188551.].

PMID- 30212581
TI  - Lower serum levels of Meteorin-like/Subfatin in patients with coronary artery
      disease and type 2 diabetes mellitus are negatively associated with insulin
      resistance and inflammatory cytokines.
AB  - Meteorin-like (Metrnl) is a newly discovered adipokine with favorable effect on
      insulin sensitivity. Previous studies have reported lower levels of Metrnl in
      obese patients. However, there is conflicting data regarding its circulating
      levels in type 2 diabetes mellitus (T2DM) and there is no data in patients with
      coronary artery disease (CAD). The aim of the present study was to evaluate the
      Metrnl serum level in patients with T2DM and CAD, and also to evaluate the serum
      levels of Metrnl with serum levels of adiponectin, IL-6 and TNF-alpha in
      patients. This study was conducted on 66 patients with CAD, 63 T2DM patients and
      41 controls. The serum levels of Metrnl, adiponectin, IL-6 and TNF-alpha were
      measured using ELISA techniques. The serum levels of Metrnl were found to be
      lower in CAD (75.18 +/- 28.48 pg/mL) and T2DM patients (73.89 +/- 33.60 pg/mL)
      compared to the control group (95.33 +/- 32.56 pg/mL) (p < 0.005 and p<0.003,
      respectively). Additionally, adiponectin decreased in CAD and T2DM patients as
      compared to the control group, while IL-6 and TNF-alpha were higher in CAD and
      T2DM patients. Metrnl showed independent association with the risk of CAD and
      T2DM presence. Furthermore, Metrnl illustrated a negative correlation with IL-6
      and TNF-alpha in both CAD patients and also with BMI, insulin resistance, IL-6
      and TNF-alpha in T2DM patients. Metrnl showed an association with CAD and T2DM
      presence and with components of their pathogenesis such as inflammation and
      insulin resistance. These results suggested a possible interaction between Metrnl
      and the pathogenesis of CAD and T2DM, however more studies are needed to prove
      this concept.

PMID- 30212583
TI  - Hypoxia impairs adaptation of skeletal muscle protein turnover- and AMPK
      signaling during fasting-induced muscle atrophy.
AB  - BACKGROUND: Hypoxemia in humans may occur during high altitude mountaineering and
      in patients suffering from ventilatory insufficiencies such as cardiovascular- or
      respiratory disease including Chronic Obstructive Pulmonary Disease (COPD). In
      these conditions, hypoxemia has been correlated to reduced appetite and decreased
      food intake. Since hypoxemia and reduced food intake intersect in various
      physiological and pathological conditions and both induce loss of muscle mass, we
      investigated whether hypoxia aggravates fasting-induced skeletal muscle atrophy
      and evaluated underlying protein turnover signaling. METHODS: Mice were kept
      under hypoxic (8% oxygen) or normoxic conditions (21% oxygen), or were pair-fed
      to the hypoxia group for 12 days. Following an additional 24 hours of fasting,
      muscle weight and protein turnover signaling were assessed in the gastrocnemius
      muscle by RT-qPCR and Western blotting. RESULTS: Loss of gastrocnemius muscle
      mass in response to fasting in the hypoxic group was increased compared to the
      normoxic group, but not to the pair-fed normoxic control group. Conversely, the
      fasting-induced increase in poly-ubiquitin conjugation, and expression of the
      ubiquitin 26S-proteasome E3 ligases, autophagy-lysosomal degradation-related mRNA
      transcripts and proteins, and markers of the integrated stress response (ISR),
      were attenuated in the hypoxia group compared to the pair-fed group. Mammalian
      target of rapamycin complex 1 (mTORC1) downstream signaling was reduced by
      fasting under normoxic conditions, but sustained under hypoxic conditions.
      Activation of AMP-activated protein kinase (AMPK) / tuberous sclerosis complex 2
      (TSC2) signaling by fasting was absent, in line with retained mTORC1 activity
      under hypoxic conditions. Similarly, hypoxia suppressed AMPK-mediated
      glucocorticoid receptor (GR) signaling following fasting, which corresponded with
      blunted proteolytic signaling responses. CONCLUSIONS: Hypoxia aggravates fasting
      induced muscle wasting, and suppresses AMPK and ISR activation. Altered AMPK
      mediated regulation of mTORC1 and GR may underlie aberrant protein turnover
      signaling and affect muscle atrophy responses in hypoxic skeletal muscle.

PMID- 30212584
TI  - Chromatin remodeling controls Kaposi's sarcoma-associated herpesvirus
      reactivation from latency.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of three
      human malignancies, the endothelial cell cancer Kaposi's sarcoma, and two B cell
      cancers, Primary Effusion Lymphoma and multicentric Castleman's disease. KSHV has
      latent and lytic phases of the viral life cycle, and while both contribute to
      viral pathogenesis, lytic proteins contribute to KSHV-mediated oncogenesis.
      Reactivation from latency is driven by the KSHV lytic gene transactivator RTA,
      and RTA transcription is controlled by epigenetic modifications. To identify host
      chromatin-modifying proteins that are involved in the latent to lytic transition,
      we screened a panel of inhibitors that target epigenetic regulatory proteins for
      their ability to stimulate KSHV reactivation. We found several novel regulators
      of viral reactivation: an inhibitor of Bmi1, PTC-209, two additional histone
      deacetylase inhibitors, Romidepsin and Panobinostat, and the bromodomain
      inhibitor (+)-JQ1. All of these compounds stimulate lytic gene expression, viral
      genome replication, and release of infectious virions. Treatment with Romidepsin,
      Panobinostat, and PTC-209 induces histone modifications at the RTA promoter, and
      results in nucleosome depletion at this locus. Finally, silencing Bmi1 induces
      KSHV reactivation, indicating that Bmi1, a member of the Polycomb repressive
      complex 1, is critical for maintaining KSHV latency.

PMID- 30212585
TI  - Correction: Blood pressure control in chronic kidney disease: A cross-sectional
      analysis from the German Chronic Kidney Disease (GCKD) study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0202604.].

PMID- 30212586
TI  - It's in the mix: Reassortment of segmented viral genomes.

PMID- 30212587
TI  - Self-assessed goal achievement (SAGA) after Holmium laser enucleation of the
      prostate (HoLEP): Association with patients' postoperative satisfaction.
AB  - This study aimed to determine serial changes in self-assessed goal achievement
      (SAGA) and treatment satisfaction after HoLEP, to identify correlations between
      the two, and to compare them with results assessed by traditional outcome
      measures. For a total of 170 patients, outcomes were evaluated serially at
      postoperative 1-, 3-, 6-, and 12-months using IPSS, OABSS, SAGA questionnaires
      and uroflowmetry. The SAGA questionnaire consisted of five questions including
      one open-ended question (self-assessed goals and degree of SAGA) and another
      question regarding treatment satisfaction. The number of self-assessed treatment
      goals was two or more in 74.1% of the patients. Most common treatment goal was
      relief from straining/hesitancy, followed by increased daytime frequency,
      nocturia and feeling of incomplete emptying. Degree of achievement for the first
      or second goal and treatment satisfaction tended to increase with time throughout
      the follow-up period. Patients with the greatest treatment satisfaction scores
      showed greater improvement by traditional outcome parameters including quality of
      life (QOL) index, total OABSS, maximum flow rate (Qmax), post-void residual urine
      volume (PVR) and bladder voiding efficiency (BVE) compared to those without
      treatment satisfaction. After adjusting for other influential variables, the
      improvements in subjective outcome parameters including total IPSS, QOL index and
      total OABSS were significantly associated with treatment satisfaction, but
      improvements in objective outcome parameters including Qmax, PVR and BVE were
      not. In addition, the degree of SAGA for the first goal or second goal was more
      predictive in determining treatment satisfaction than the traditional outcome
      measures. In conclusion, treatment goals of patients with lower urinary tract
      symptoms (LUTS)/BPH vary from individual to individual. The degree of SAGA and
      treatment satisfaction for HoLEP tends to increase with time throughout the
      follow-up period. Compared to the traditional outcome measures, the degree of
      goal achievement can be more predictive when assessing patient-centered outcomes
      such as treatment satisfaction.

PMID- 30212588
TI  - Bias caused by sampling error in meta-analysis with small sample sizes.
AB  - BACKGROUND: Meta-analyses frequently include studies with small sample sizes.
      Researchers usually fail to account for sampling error in the reported within
      study variances; they model the observed study-specific effect sizes with the
      within-study variances and treat these sample variances as if they were the true
      variances. However, this sampling error may be influential when sample sizes are
      small. This article illustrates that the sampling error may lead to substantial
      bias in meta-analysis results. METHODS: We conducted extensive simulation studies
      to assess the bias caused by sampling error. Meta-analyses with continuous and
      binary outcomes were simulated with various ranges of sample size and extents of
      heterogeneity. We evaluated the bias and the confidence interval coverage for
      five commonly-used effect sizes (i.e., the mean difference, standardized mean
      difference, odds ratio, risk ratio, and risk difference). RESULTS: Sampling error
      did not cause noticeable bias when the effect size was the mean difference, but
      the standardized mean difference, odds ratio, risk ratio, and risk difference
      suffered from this bias to different extents. The bias in the estimated overall
      odds ratio and risk ratio was noticeable even when each individual study had more
      than 50 samples under some settings. Also, Hedges' g, which is a bias-corrected
      estimate of the standardized mean difference within studies, might lead to larger
      bias than Cohen's d in meta-analysis results. CONCLUSIONS: Cautions are needed to
      perform meta-analyses with small sample sizes. The reported within-study
      variances may not be simply treated as the true variances, and their sampling
      error should be fully considered in such meta-analyses.

PMID- 30212589
TI  - Correction: Preferring more e-cigarette flavors is associated with e-cigarette
      use frequency among adolescents but not adults.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189015.].

PMID- 30212591
TI  - Association of HindIII-polymorphism in kappa-casein gene with milk, fat and
      protein yield in holstein cattle.
AB  - The aim of this paper was to evaluate the effect of genetic polymorphism of kappa
      casein on milk production in Holstein cattle. Two hundred and ten Holstein cows
      were used in this study. We established genotype structure of cattle population
      and calculated allelic frequencies based on PCR-RFLP analyses. The three
      genotypes: AA (69.52%), AB (27.62%), and BB (2.86%) were detected. Frequency of
      allele A was 83.33%, and of allele B 16.67%. The Holstein cattle kept in Slovak
      Republic exhibit a high value of homozygosity (0.7222) and low values of
      polymorphism information content (0.2392), effective number of alleles (1.3847)
      and level of possible variability realization (27.91%). The effect of
      polymorphism of CSN3 gene on average breeding values for milk production traits,
      such as yield of milk, fat and protein expressed in kilograms, as well as
      percentage content of fat and protein in milk, has been assessed. In our
      assessment of the observed traits' variability's dependence on CSN3 gene
      polymorphism, we detected a statistically significant difference between
      genotypes only in case of the average breeding value for the percentage of
      protein in milk.

PMID- 30212590
TI  - Impact of human sepsis on CCCTC-binding factor associated monocyte
      transcriptional response of Major Histocompatibility Complex II components.
AB  - BACKGROUND: Antigen presentation on monocyte surface to T-cells by Major
      Histocompatibility Complex, Class II (MHC-II) molecules is fundamental for
      pathogen recognition and efficient host response. Accordingly, loss of Major
      Histocompatibility Complex, Class II, DR (HLA-DR) surface expression indicates
      impaired monocyte functionality in patients suffering from sepsis-induced
      immunosuppression. Besides the impact of Class II Major Histocompatibility
      Complex Transactivator (CIITA) on MHC-II gene expression, X box-like (XL)
      sequences have been proposed as further regulatory elements. These elements are
      bound by the DNA-binding protein CCCTC-Binding Factor (CTCF), a superordinate
      modulator of gene transcription. Here, we hypothesized a differential interaction
      of CTCF with the MHC-II locus contributing to an altered monocyte response in
      immunocompromised septic patients. METHODS: We collected blood from six patients
      diagnosed with sepsis and six healthy controls. Flow cytometric analysis was used
      to identify sepsis-induced immune suppression, while inflammatory cytokine levels
      in blood were determined via ELISA. Isolation of CD14++ CD16-monocytes was
      followed by (i) RNA extraction for gene expression analysis and (ii) chromatin
      immunoprecipitation to assess the distribution of CTCF and chromatin
      modifications in selected MHC-II regions. RESULTS: Compared to healthy controls,
      CD14++ CD16-monocytes from septic patients with immune suppression displayed an
      increased binding of CTCF within the MHC-II locus combined with decreased
      transcription of CIITA gene. In detail, enhanced CTCF enrichment was detected on
      the intergenic sequence XL9 separating two subregions coding for MHC-II genes.
      Depending on the relative localisation to XL9, gene expression of both regions
      was differentially affected in patients with sepsis. CONCLUSION: Our experiments
      demonstrate for the first time that differential CTCF binding at XL9 is
      accompanied by uncoupled MHC-II expression as well as transcriptional and
      epigenetic alterations of the MHC-II regulator CIITA in septic patients. Overall,
      our findings indicate a sepsis-induced enhancer blockade mediated by variation of
      CTCF at the intergenic sequence XL9 in altered monocytes during
      immunosuppression.

PMID- 30212592
TI  - NLCs as a potential carrier system for transdermal delivery of forskolin.
AB  - Nanostructured lipid carriers (NLC) composed of the substances generally
      recognized as safe (GRAS) were obtained by using a hot high-pressure
      homogenization technique (HPH). The influence of the number of homogenization
      cycles and concentration of a decyl glucoside surfactant on the NLC properties
      were studied. The system's stability was assessed by macroscopic observation,
      light backscattering and zeta potential measurements. NLC particle size was
      measured using dynamic light scattering (DLS). The kinetically stable
      formulations were loaded with forskolin and selected for in vitro drug permeation
      study using the Franz cell method. Concentration of forskolin in the receptor
      solution (i.e. ethanol/PBS mixture) was analyzed with high performance liquid
      chromatography (HPLC) with UV detection. The obtained results have shown that NLC
      formulations could be used as effective carriers for forskolin permeation through
      the skin.

PMID- 30212593
TI  - Influence of oleic acid in different solvent media on BRL 3A cell growth and
      viability.
AB  - Oleic acid (OA) is widely used in pathology studies of hepatocellular lipid
      deposition. Identifying the effects of different solvents on OA-induced liver
      lipid deposition would be beneficial for studies on hepatocytes. We treated BRL
      3A cells with OA dissolved in different solvents. After 12 h incubation, cell
      viability was assessed using MTT assays. Reactive oxygen species (ROS),
      triglyceride (TG) and total cholesterol (TC) counts, and the expression level of
      glucose regulated protein (GRP78), sterol regulatory element binding protein
      (SREBP-1C) and fatty acid synthase (FAS) were analyzed. Water, PBS and DMSO were
      disadvantageous to the dissolution of OA and did not cause an OA-induced response
      in hepatocytes. In the alcohol+OA-treated cells, the severe ER stress, oxidative
      stress and cellular fat deposition were significantly increased. BSA promoted
      cell growth and the cells treated with 1.2% BSA+OA showed a lower grade TG and
      endoplasmic reticulum stress compared with KOH+OA and alcohol+OA treatments. KOH
      had no significant influence on BRL 3A cells viability. When treated with OA
      dissolved in KOH, BRL 3A cells showed a typical hepatocyte damage. KOH was
      considered the suitable choice for an OA solvent for BRL 3A cells in hepatic
      lipidosis research.

PMID- 30212594
TI  - Chlamydial genomic MinD protein does not regulate plasmid-dependent genes like
      Pgp5.
AB  - Chlamydia has a unique intracellular developmental cycle, which has hindered the
      single protein function study of Chlamydia. Recently developed transformation
      system of Chlamydia has greatly advanced the chlamydial protein's function
      research and was used to find that a chlamydial plasmid-encoded Pgp5 protein can
      down-regulate plasmid-dependent genes. It is assumed, that chlamydial genomic
      MinD protein has a similar function to Pgp5. However, it is unknown whether MinD
      protein regulates the same plasmid-dependent genes. We replaced pgp5 gene in the
      shuttle vector pGFP::CM with minD gene of C. trachomatis (CT0582) or C. muridarum
      (TC0871). The recombinant plasmid was transformed into plasmid-free organisms
      CMUT3 and qRT-PCR was used to detect the transcription level of plasmid-encoded
      and -dependent genes in these pgp5 deficient organisms. As a readout, GlgA, one
      of the plasmid-regulated gene products was detected by immunofluorescence assay.
      After recombination, transformation and plaque purification, the stable
      transformants CT0582R and TC0871R were generated. In these transformants, the
      plasmid-dependent genes were up-regulated, alike in the pgp5 premature stop
      mutant and pgp5 replacement with mCherry mutant. GlgA protein level was also
      increased in all pgp5 mutants, including CT0582R and TC0871R. Thus, our study
      showed that genomic MinD protein had different function than Pgp5, which was
      useful for further understanding the chlamydiae.

PMID- 30212596
TI  - In Response to "Normalization of Plus Size and the Danger of Unseen Overweight
      and Obesity in England".

PMID- 30212595
TI  - Pancreaticoduodenectomy and metastasectomy for metastatic pancreatic
      neuroendocrine tumors.
AB  - BACKGROUND AND OBJECTIVES: Various treatment options exist for patients with
      metastatic pancreatic neuroendocrine tumors (PNETs). Surgical resection with
      pancreaticoduodenectomy (PD) typically reserved for patients with limited
      disease. Definitive data are lacking to support either the resection of primary
      PNET in the metastatic setting or for surgical debulking of metastatic lesions.
      METHODS: We conducted an analysis of the National Cancer Database (NCDB) using
      the pancreatic cancer Participant User File. Thirty- and 90-day mortality rates
      and survival rates were determined for patients undergoing PD for primary tumor
      resection and compared with patients who had no surgery or metastasectomy. The
      Kaplan-Meier method was used to compare survival time. Cox regression models were
      used to assess factors independently associated with overall survival time.
      RESULTS: Resection of the primary tumor or metastatic disease each significantly
      improved overall survival time compared with no resection. Adding metastasectomy
      to PD resulted in an incremental increase in overall survival time. Both PD and
      metastasectomy are independently associated with overall survival time.
      CONCLUSIONS: Our report highlights the potential for survival time benefit in
      appropriately selected patients who undergo PD in the setting of metastatic PNET.

PMID- 30212598
TI  - Nipple-sparing mastectomy and breast reconstruction with a deep inferior
      epigastric perforator flap using thoracodorsal recipient vessels and a low
      lateral incision.
AB  - BACKGROUND: Nipple-sparing mastectomy poses challenges in providing esthetically
      pleasing immediate autologous breast reconstruction. This study was to
      investigate the outcomes of nipple-sparing mastectomy with breast reconstruction
      using free abdominal flaps between two different recipient sites. METHODS:
      Between 2010 and 2016, 79 patients who underwent nipple-sparing mastectomy with
      autologous breast reconstruction using thoracodorsal (TD) vessels in 30 cases or
      internal mammary (IM) vessels in 49 cases were investigated. Demographics,
      intraoperative findings, complications, and quality of life using Breast-Q
      questionnaire were compared between two groups. RESULTS: All flap survived. There
      was no statistical difference in age, BMI, ischemia time, and flap-used
      percentage. The TD artery had a statistically smaller diameter 1.8 +/- 0.4 mm
      than the IM artery 2.7 +/- 0.43 mm (p = 0.02). At a mean follow-up of 44.4 +/-
      35.2 months, there was no statistical difference in total complication rates
      between TD and IM groups (23.3% and 36.7%, respectively, p > 0.05). The
      "psychosocial well-being" of Breast-Q in TD group 83.9 +/- 14.6 was statistically
      greater than IM group 72.8 +/- 17.6 (p = 0.04). CONCLUSIONS: Nipple-sparing
      mastectomy with immediate breast reconstruction using TD vessels with a low
      lateral scar is a safe procedure that provides an inconspicuous scar with better
      cosmesis and minimal complication rate.

PMID- 30212597
TI  - Introducing fluorescence guided surgery into orthopedic oncology: A systematic
      review of candidate protein targets for Ewing sarcoma.
AB  - Ewing sarcoma (ES), an aggressive bone and soft-tissue tumor, is treated with
      chemotherapy, radiotherapy, and surgery. Intra-operative distinction between
      healthy and tumorous tissue is of paramount importance but challenging,
      especially after chemotherapy and at complex anatomical locations. Near infrared
      (NIR) fluorescence-guided surgery (FGS) is able to facilitate the determination
      of tumor boundaries intra-operatively, improving complete resection and therefore
      survival. This review evaluates potential ES-specific proteins from the
      literature as targets for NIR FGS.

PMID- 30212599
TI  - Recovery of cortical volume and thickness after remission from acute anorexia
      nervosa.
AB  - OBJECTIVE: Reduced grey (GM) and white matter (WM) volumes and increased
      cerebrospinal fluid (CSF) have been frequently reported in anorexia nervosa (AN),
      but studies focusing on cortical thickness (CT) are scarce and findings
      inconsistent. We conducted the first study in AN that analyzed both parameters in
      the same study to gain novel and comprehensive insight. METHOD: Voxel-based
      morphometry (VBM) analysis was performed on T1-weighted magnetic resonance images
      from 34 predominantly adult women with acute AN, 24 REC participants, and 41
      healthy controls (HC). Global brain segment volumes (GM, WM, and CSF), regional
      GM volume, and cortical thickness measures were obtained from the same study
      sample. We further focused on recovery by including a REC group. RESULTS: The GM
      and WM volumes were decreased, and correspondingly, the CSF volume increased in
      the AN in comparison to the HC and REC groups. No significant volume differences
      between the REC and HC groups could be observed. AN patients showed reduced
      regional GM volumes in the right hippocampus and the left middle and right
      inferior frontal gyrus. Cortical thinning occurred in the AN group, which was
      particularly robust in fronto-parietal areas. The REC and HC groups failed to
      show any regional GM or cortical thickness differences. DISCUSSION: AN is
      accompanied by severe loss of brain volume and cortical thickness as assessed by
      complementary investigation tools. However, these changes seem to be largely
      reversible, which should be encouraging for therapists and patients. The
      underlying neurobiological mechanisms remain unclear and should be assessed in
      further studies.

PMID- 30212600
TI  - Lymph node metastases in splenic flexure colon cancer: Is subtotal colectomy
      warranted?
AB  - BACKGROUND AND OBJECTIVES: Tumors of the splenic flexure (TSF) can be associated
      with metastatic lymph nodes (LN) along the left colic pedicle, but also along the
      superior mesenteric vessels. We aimed to detail the anatomical distribution of
      metastatic LNs in patients undergoing elective subtotal colectomy for TSF.
      METHOD: Between 2000 and 2016, 65 patients were included. At pathological
      analysis, LNs were classified into two groups: locoregional LN (along the left
      colic artery) and distant LN (along the middle colic, right colic, and ileocolic
      arteries). RESULTS: The median number of LNs examined was 20. Eighteen patients
      (27%) were pN+. Among them, six (33% of pN+ patients and 9% of the series) had at
      least one positive distant LN. All these patients had a positive distant LN along
      the right colic artery. These patients had a significantly advanced stage and
      more positive LNs than the others (stage III-IV: 100% vs 22%, P = 0.0009 and 6 [3
      15] vs 0 [0-15], P < 0.0001, respectively). The presence of synchronous
      metastases was predictor of metastatic distant LNs (P = 0.042). CONCLUSION:
      Elective subtotal colectomy for TSF allows to discover distant positive LNs in
      nearly 10% of patients. For those having TSF and synchronous metastatic disease
      enable to resection, subtotal colectomy should be recommended.

PMID- 30212601
TI  - A Functional Comparison of Treatment of Intrinsic Sphincter Deficiency with
      Muscle-Derived and Adipose Tissue-Derived Stem Cells.
AB  - This study investigated the effect of muscle-derived stem cells (MDSCs) and
      adipose tissue-derived stem cells (ADSCs) in the treatment of stress urinary
      incontinence (SUI) and their differences in a rat model. MDSCs and ADSC were
      isolated from rats (n = 10), examined for their properties, and labeled with
      enhanced green fluorescent protein (EGFP) and beta-galactosidase (beta-gal) gene.
      Rats received bladder-neck and transurethral sphincter injection of EGFP-labeled
      MDSCs and beta-gal gene-labeled ADSC and injection of D-Hanks as a control (n =
      24 each group). At 0, 15, 30, and 60 days after cells injection, urinary voiding
      function was assessed by urine dynamics detector. The rats were killed to harvest
      their urethras for tracking of MDSCs and ADSC. Western blotting and quantitative
      real-time reverse transcription PCR (qRT-PCR) was performed to detect smooth
      muscle contents. Urodynamic test showed that MDSCs and ADSC improved the function
      of urination in rats with intrinsic sphincter deficiency (ISD), and effect of
      MDSCs-treatment was more pronounced. In addition, histologic analysis showed that
      the MDSCs and ADSC-treated groups had significantly higher myosin and alpha
      smooth muscle actin (alpha-SMA) content than the control group. Compared with
      ADSC-treated groups, the MDSCs-treated groups in myosin and alpha-SMA content
      showed the tendency of increase. In summary, MDSCs and ADSCs have obvious effects
      in the treatment and/or prevention of ISD and transplantation of MDSCs is more
      effective than ADSC. (c) 2018 IUBMB Life, 70(10):976-984, 2018.

PMID- 30212602
TI  - Flow Cytometric Monitoring for Residual Disease in B Lymphoblastic Leukemia Post
      T Cell Engaging Targeted Therapies.
AB  - The use of targeted therapy is growing in the setting of hematopoietic neoplasms.
      Flow cytometry is a cornerstone of residual disease monitoring post therapy in
      this group of malignancies. Often, there is overlap between antigens targeted by
      immunotherapies and gating reagents utilized for population identification by
      flow cytometry. Such overlap can render a previously excellent gating reagent
      inadequate for disease detection. Recently, several anti-CD19 T cell-engaging
      immunotherapeutic agents and an anti-CD22 immunotoxin have been FDA approved for
      use in B lymphoblastic leukemia (B-LL), with an anti-CD22 T cell-engaging agent
      in development. In the setting of such targeted therapies, CD19 and CD22
      expression may be altered, compromising the use of these reagents for
      identification of abnormal blasts. We describe herein a strategy for flow
      cytometric monitoring for residual disease in patients with B-LL post T cell
      engaging anti-CD19 and anti-CD22 therapies. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30212603
TI  - Preparation of Ligand-Targeted Drug Conjugates for Cancer Therapy and Their
      Evaluation In Vitro.
AB  - Present treatment strategies focus on minimizing unwanted toxicity to healthy
      cells during chemotherapeutic treatment. This is achieved by developing
      strategies to selectively deliver drugs to malignant cells over-expressing
      specific protein biomarkers. The drugs are attached via a self-immolative linker
      to a small molecule homing ligand having affinity for protein biomarkers over
      expressed during disease states. Several such targeting-ligand drug conjugates
      have now reached preclinical and clinical trials, and this article aims to show a
      general methodology to prepare the same. Using solid-phase peptide synthesis
      (SPPS) methodology, the targeting ligand is covalently linked to a peptide spacer
      having appropriate hydrophobic and hydrophilic amino acids. The targeting ligand
      attached peptide spacer is next conjugated with the required drug molecule
      through a cleavable disulfide bond in a solution-phase reaction. This protocol
      further elucidates the step-by-step procedures to be followed for complete
      evaluation of newly synthesized ligand-targeted drug conjugates in vitro. (c)
      2018 by John Wiley & Sons, Inc.

PMID- 30212604
TI  - TeamSTEPPS(r) : An evidence-based approach to reduce clinical errors threatening
      safety in outpatient settings: An integrative review.
AB  - OBJECTIVE: The objective of this integrative review of literature was to
      investigate and evaluate feasibility and potential for success of TeamSTEPPS(r)
      implementation, the influence of TeamSTEPPS for Office-Based Care on the clinical
      error rate in a private outpatient clinic, and influence of TeamSTEPPS for Office
      Based Care on patient satisfaction. BACKGROUND: Patient safety remains a top
      priority for all health care providers in all clinical settings. Despite multiple
      varied efforts, clinical errors directly attributed to communication are
      consistently at the top of the list of root causes, although improvement
      strategies such as Team Strategies and Tools to Enhance Performance and Patient
      Safety (TeamSTEPPS) have been implemented, there is insufficient data reported
      measuring the influence of this intervention on patient safety, clinical errors
      related to communication, and patient satisfaction. SEARCH STRATEGY: A systematic
      search of the electronic databases MEDLINE Complete, CINAHL Complete, Embase, and
      Science Direct was conducted to seek literature that reported the effectiveness
      of the TeamSTEPPS tool to reduce clinical errors, improve communication, and
      increase patient satisfaction. Nineteen studies met inclusion criteria. Levels of
      evidence for each study was determined using the 2009 American Association of
      Critical Care Nursing (AACN) levels. CONCLUSIONS: The present review is
      consistent with marked improvement in communication, decrease in clinical error
      rates, and improvement in patient satisfaction. There is a significant need for
      evaluation of the impact of this validated toolkit from the Agency for Healthcare
      Research and Quality to maintain a sustainable health care environment for all
      stakeholders. As a result of this integrative review, a quality improvement
      project related to both the primary and secondary end points is in progress.

PMID- 30212605
TI  - The Alcohol-to-Jet Conversion Pathway for Drop-In Biofuels: Techno-Economic
      Evaluation.
AB  - The alcohol-to-jet (ATJ) process is a method for the conversion of alcohols to an
      alternative jet fuel blendstock based on catalytic steps historically utilized by
      the petroleum refining and petrochemical industry. This pathway provides a means
      for producing a sustainable alternative jet fuel (SAJF) from a wide variety of
      resources and offers a near-term opportunity for alcohol producers to enter the
      SAJF market and for the aviation sector to meet growing SAJF demand. Herein, the
      technical background is reviewed and selected variations of ATJ processes
      evaluated. Simulation and modeling were employed to assess some ATJ conversion
      schemes, with a particular focus on comparisons between the use of an ethanol or
      isobutanol intermediate. Although the utilization of isobutanol offers a 34 %
      lower conversion cost for the catalytic upgrading process, the cost of alcohol
      production is estimated to contribute more than 80 % of the total cost at the
      refinery. The cost of feedstock and alcohol production has a dominant effect on
      the overall process economics.

PMID- 30212606
TI  - Impact of teamwork improvement training on communication and teamwork climate in
      ambulatory reproductive health care.
AB  - BACKGROUND: While team training is associated with improved hospital-based team
      climate, less is known about effects in the ambulatory setting. STUDY DESIGN: In
      2014 and 2015, we enrolled 20 organizations, each operating various health
      centers, into this ongoing study. Evaluation tools include a communication
      behaviors assessment (CBA) and Team Strategies and Tools to Enhance Performance
      and Patient Safety (TeamSTEPPS(r) ) Teamwork Perceptions Questionnaire (T-TPQ),
      which staff completes at baseline, 6 months, and 1 year, and the Patients'
      Insights and Views of Teamwork (PIVOT) survey, which patients complete at
      baseline and 1 year. We also assessed patient satisfaction. We analyzed T-TPQs
      paired at the individual level and CBAs and PIVOTs paired at the health center
      level. We also conducted key informant interviews with the first cohort. RESULTS:
      CBAs showed that TeamSTEPPS tools and strategies were utilized, with 50% or more
      of centers reporting increases in all behaviors at 1 year; key informant
      interviews confirmed this. T-TPQ findings indicated that TeamSTEPPS
      implementation was associated with improved staff perceptions of teamwork at 6
      months; lesser improvements were seen at 1 year. The PIVOT survey demonstrated
      significant improvements in select patient ratings of teamwork. Patient
      satisfaction improved at 1 year. CONCLUSIONS: TeamSTEPPS has positive effects in
      the ambulatory reproductive health care environment. Improvements persisted at 1
      year.

PMID- 30212607
TI  - Contribution of bacterial effectors and host proteins to the composition and
      function of Salmonella-induced tubules.
AB  - Cells infected with Salmonella are characterised by the appearance of membrane
      tubular structures that stretch from the bacterial vacuole. The formation of
      these tubules requires the translocation of Salmonella effector proteins within
      the infected cell. Different types of Salmonella-induced tubules with varying
      host protein compositions have been identified. This variability probably
      reflects the ability of these tubules to interact with different host
      compartments. Membrane tubules decorated with effector proteins but essentially
      devoid of host proteins and named LAMP1-negative (LNT) were observed. LNTs wrap
      around LAMP1-positive vesicles and may promote recruitment of lysosomal
      glycoproteins to bacterial vacuole and the formation of a replication niche. We
      conducted a biochemical and functional characterisation of LNTs. We show that the
      effector proteins SseF and SseG are necessary for their formation. The absence of
      these tubules is associated with decreased recruitment of LAMP1 to SCVs,
      decreased intracellular replication of Salmonella, and decreased virulence in
      mice. We found that the process leading to the recruitment of lysosomal
      glycoproteins to tubules involves the C-terminal domain of the effector protein
      SifA and the GTPase Arl8b. Overall, these data suggest that Salmonella-induced
      tubules promote the establishment of the replication niche by promoting
      recruitment of host proteins to the bacterial vacuole.

PMID- 30212608
TI  - Physical Activity Modulates the Overexpression of the Inflammatory miR-146a-5p in
      Obese Patients.
AB  - Specific microRNAs (miRs), including the "angio-miR-126" and the "inflamma-miR
      146a-5p," have been proposed as biomarkers and even therapeutic targets of
      obesity-associated metabolic diseases. Physical activity, a key measure of
      prevention for obesity and its complications, is reported to influence the
      expression of these miRs. In this study, we investigate whether a physical
      activity program proven to improve metabolic parameters in obese patients can
      correct the circulating levels of these miRs. Plasma miR-126 and miR-146a-5p were
      measured in a cohort of obese patients (n = 31, 16F + 15M) before and after the 3
      month physical activity program of the CURIAMO trial (registration number for
      clinical trials: ACTRN12611000255987) and in 37 lean controls (24F + 13M). miR
      146a-5p, but not miR-126, was significantly increased in obese patients as
      compared with lean controls and decreased in approximately two-thirds of the
      participants post-intervention with a response that positively correlated with
      pre-intervention levels of this miR. Waist circumference, the inflammatory
      cytokine IL-8 and lipid parameters, principally total cholesterol, showed the
      strongest correlation with both the baseline levels and post-intervention
      correction of miR-146a-5p. Post-hoc analysis of experimental data supports the
      use of miR-146a-5p as a biomarker and predictor of the clinical response to
      physical activity in obese patients. Furthermore, miR-146a-5p expression was
      confirmed to increase together with that of the inflammatory genes TLR4, NF
      kappaB, IL-6, and TNF-alpha in LPS-stimulated human mononuclear leukocytes. In
      conclusion, the inflamma-miR-146a-5p can serve as a personalized predictor of
      clinical outcome in obese patients entering physical activity weight-reduction
      programs. (c) 2018 IUBMB Life, 70(10):1012-1022, 2018.

PMID- 30212609
TI  - When the Surface Matters: Prebiotic Peptide-Bond Formation on the TiO2 (101)
      Anatase Surface through Periodic DFT-D2 Simulations.
AB  - The mechanism of the peptide-bond formation between two glycine (Gly) molecules
      has been investigated by means of PBE-D2* and PBE0-D2* periodic simulations on
      the TiO2 (101) anatase surface. This is a process of great relevance both in
      fundamental prebiotic chemistry, as the reaction univocally belongs to one of the
      different organizational events that ultimately led to the emergence of life on
      Earth, as well as from an industrial perspective, since formation of amides is a
      key reaction for pharmaceutical companies. The efficiency of the surface
      catalytic sites is demonstrated by comparing the reactions in the gas phase and
      on the surface. At variance with the uncatalyzed gas-phase reaction, which
      involves a concerted nucleophilic attack and dehydration step, on the surface
      these two steps occur along a stepwise mechanism. The presence of surface Lewis
      and Bronsted sites exerts some catalytic effect by lowering the free energy
      barrier for the peptide-bond formation by about 6 kcal mol-1 compared to the gas
      phase reaction. Moreover, the co-presence of molecules acting as proton-transfer
      assistants (i.e., H2 O and Gly) provide a more significant kinetic energy barrier
      decrease. The reaction on the surface is also favorable from a thermodynamic
      standpoint, involving very large and negative reaction energies. This is due to
      the fact that the anatase surface also acts as a dehydration agent during the
      condensation reaction, since the outermost coordinatively unsaturated Ti atoms
      strongly anchor the released water molecules. Our theoretical results provide a
      comprehensive atomistic interpretation of the experimental results of Martra et
      al. (Angew. Chem. Int. Ed. 2014, 53, 4671), in which polyglycine formation was
      obtained by successive feedings of Gly vapor on TiO2 surfaces in dry conditions
      and are, therefore, relevant in a prebiotic context envisaging dry and wet cycles
      occurring, at mineral surfaces, in a small pool.

PMID- 30212610
TI  - A General Amino Acid Synthesis Enabled by Innate Radical Cross-Coupling.
AB  - The direct union of primary, secondary, and tertiary carboxylic acids with a
      chiral glyoxylate-derived sulfinimine provides rapid access into a variety of
      enantiomerically pure alpha-amino acids (>85 examples). Characterized by
      operational simplicity, this radical-based reaction enables the modular assembly
      of exotic alpha-amino acids, including both unprecedented structures and those of
      established industrial value. The described method performs well in high
      throughput library synthesis, and has already been implemented in three distinct
      medicinal chemistry campaigns.

PMID- 30212611
TI  - In Vivo Evaluation of Ligand Targeted Drug Conjugates for Cancer Therapy.
AB  - The development of small molecule ligand-targeted therapeutics is currently of
      paramount importance for treatment of cancer due to their potential to reduce
      system toxicity and increase potency of a delivered chemotherapeutic drug. The
      main aim of a targeted drug-delivery technique is to release the drug cargo
      selectively into tumor tissues, avoiding off-site toxicity to healthy tissues and
      organs during chemotherapy. In this strategy, a chemotherapeutic drug is
      conjugated to a homing ligand, which has high affinity for proteins over
      expressed on cancer cells, via a peptide linker and a self-immolative segment
      that facilitates intracellular release of drug cargo. During development of
      targeted drug conjugates, preclinical evaluation in tumor models of small animals
      like mice adds valuable data on the clinical performance of the drug. This
      article contains a set of protocols for implantation of tumor, determination of
      optimum dosage required for effective treatment, and estimation of maximum
      tolerated dose required for any visible side effects during treatment of cancer
      in tumor models of mice. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30212612
TI  - When do Children with Autism Spectrum Disorder Take Common Ground into Account
      During Communication?
AB  - One feature of autism spectrum disorder (ASD) is a deficit in verbal reference
      production, that is, providing an appropriate amount of verbal information for
      the listener to refer to things, people, and events. However, very few studies
      have manipulated whether individuals with ASD can take a speaker's perspective to
      interpret verbal reference. A critical limitation of all interpretation studies
      is that comprehension of another's verbal reference required the participant to
      represent only the other's visual perspective. Yet, many everyday interpretations
      of verbal reference require knowledge of social perspective (i.e., a
      consideration of which experiences one has shared with which interlocutor). We
      investigated whether 22 5;0-7;11-year-old children with ASD and 22 well-matched
      typically developing (TD) children used social perspective to comprehend (Study
      1) and produce (Study 2) verbal reference. Social perspective-taking was
      manipulated by having children collaboratively complete activities with one of
      two interlocutors such that for a given activity, one interlocutor was
      Knowledgeable and one was Naive. Study 1 found no between-group differences for
      the interpretation of ambiguous references based on social perspective. In Study
      2, when producing referring terms, the ASD group made modifications based on
      listener needs, but this effect was significantly stronger in the TD group.
      Overall, the findings suggest that high-functioning children with ASD know with
      which interlocutor they have previously shared a given experience and can take
      this information into account to steer verbal reference. Nonetheless, they show
      clear performance limitations in this regard relative to well-matched controls.
      Autism Res 2018, 11: 1366-1375. (c) 2018 International Society for Autism
      Research, Wiley Periodicals, Inc. LAY SUMMARY: No one had studied if young
      children with autism spectrum disorder (ASD) could take into account previous
      collaboration with particular conversation partners to drive how well they
      communicate with others. In both their language understanding and spoken
      language, we found that five to 7-year-olds with ASD were able to consider what
      they had previously shared with the conversation partner. However, they were
      impaired when compared to typically developing children in the degree to which
      they tailored their spoken language for a specific listener.

PMID- 30212613
TI  - The Hattie Hemschemeyer Award 2018: Nancy K. Lowe, CNM, PhD, FACNM, FAAN.

PMID- 30212614
TI  - Chemotherapy for Fighting Schistosomiasis: Past, Present and Future.
AB  - Chemotherapy based on repeated doses of praziquantel remains the most effective
      control strategy against schistosomiasis, a neglected tropical disease caused by
      platyhelminths of the genus Schistosoma spp. Its long-term use, however, raises
      serious concerns about drug resistance against praziquantel. Therefore, it is
      generally acknowledged that alternative treatment options are urgently needed.
      This Review summarizes data on relinquished drugs as well as recent advances in
      the area of antischistosomal compounds from a medicinal chemistry point of view.
      Furthermore, insights into the structure-activity relationships of each class of
      compounds are presented including in vitro and in vivo data, if available.
      Although many compounds have demonstrated good antischistosomal activity in
      vitro, they offer little promise to replace praziquantel. Nevertheless, the race
      to develop novel antischistosomal agents is ongoing.

PMID- 30212615
TI  - A Catch-and-Release Approach to Selective Modification of Accessible Tyrosine
      Residues.
AB  - The tyrosine side chain is amphiphilic leading to significant variations in the
      surface exposure of tyrosine residues in the folded structure of a native
      sequence protein. This variability can be exploited to give residue-selective
      functionalization of a protein substrate by using a highly reactive diazonium
      group tethered to an agarose-based resin. This novel catch-and-release approach
      to protein modification has been demonstrated for proteins with accessible
      tyrosine residues, which are compared with a control group of proteins in which
      there are no accessible tyrosine residues. MS analysis of the modified proteins
      showed that functionalization was highly selective, but reactivity was further
      attenuated by the electrostatic environment of any individual residue. Automated
      screening of PDB structures allows identification of potential candidates for
      selective modification by comparison with the accessibility of the tyrosine
      residue in a benchmark peptide (GYG).

PMID- 30212616
TI  - Corrigendum.

PMID- 30212617
TI  - Shapiro's seventh law.

PMID- 30212618
TI  - Analytical Methods for Deciphering RNA Modifications.

PMID- 30212619
TI  - New Generation of Clickable Nucleic Acids: Synthesis and Active Hybridization
      with DNA.
AB  - Due to the ability to generate oligomers of precise sequence, sequential and
      stepwise solid-phase synthesis has been the dominant method of producing DNA and
      other oligonucleotide analogues. The requirement for a solid support, however,
      and the physical restrictions of limited surface area thereon significantly
      diminish the efficiency and scalability of these syntheses, thus, negatively
      affecting the practical applications of synthetic polynucleotides and other
      similarly created molecules. By employing the robust photoinitiated thiol-ene
      click reaction, we developed a new generation of clickable nucleic acids (CNAs)
      with a polythioether backbone containing repeat units of six atoms, matching the
      spacing of the phosphodiester backbone of natural DNA. A simple, inexpensive, and
      scalable route was utilized to produce CNA monomers in gram-scale, which
      indicates the potential to dramatically lower the cost of these DNA mimics and
      thereby expand the scope of these materials. The efficiency of this approach was
      demonstrated by the completion of CNA polymerization in 30 seconds, as
      characterized by size-exclusive chromatography (SEC) and infrared (IR)
      spectroscopy. CNA/DNA hybridization was demonstrated by gel electrophoresis and
      used in CdS nanoparticle assembly.

PMID- 30212620
TI  - Boolean Computation in Plants Using Post-translational Genetic Control and a
      Visual Output Signal.
AB  - Due to autotrophic growing capacity and extremely rich secondary metabolism,
      plants should be preferred targets of synthetic biology. However, developments in
      plants usually run below those in other taxonomic groups. In this work we
      engineered genetic circuits capable of logic YES, OR and AND Boolean computation
      in plant tissues with a visual output signal. The circuits, which are deployed by
      means of Agrobacterium tumefaciens, perform with the conditional activity of the
      MYB transcription factor Rosea1 from Antirrhinum majus inducing the accumulation
      of anthocyanins, plant endogenous pigments that are directly visible to the naked
      eye or accurately quantifiable by spectrophotometric analysis. The translational
      fusion of Rosea1 to several viral proteins, such as potyvirus NIb or fragments
      thereof, rendered the transcription factor inactive. However, anthocyanin
      accumulation could be restored by inserting protease cleavage sites between both
      moieties of the fusion and by coexpressing specific proteases, such as potyvirus
      nuclear inclusion a protease.

PMID- 30212621
TI  - How Entanglement of Different Physicochemical Properties Complicates the
      Prediction of in Vitro and in Vivo Interactions of Gold Nanoparticles.
AB  - The physicochemical properties of a set of 21 different gold nanoparticles
      (spherical and rod-shaped nanoparticles (NPs) of different diameters with three
      different surface coatings) were studied. Protein corona formation, in vitro
      uptake, effect on cell viability and proliferation, and in vivo biodistribution
      of these NPs were determined. The relation of the results of the different NPs
      was analyzed by hierarchical cluster analysis, which will tell which NPs have the
      most similar physicochemical properties and biological effects, without having to
      specify individual physicochemical parameters. The results show that the
      physicochemical properties of gold nanoparticles (Au NPs) are mainly accounted
      for by their hydrodynamic diameter and their zeta-potential. The formation of the
      protein corona is determined by the pH-dependence of their zeta-potential. While
      several reports found that in vitro uptake and in vivo biodistribution of NPs are
      correlated to individual physicochemical parameters, e. g., size, shape, or
      surface chemistry, such direct dependence in the investigated multidimensional
      set of NPs was not found in our study. This most likely is due to entanglement of
      the different parameters, which complicates the prediction of the biological
      effect of NPs in case multiple physicochemical properties are simultaneously
      varied. The in vitro uptake and in vivo biodistribution of NPs seem to be not
      directly driven by the protein corona, but the physicochemical properties
      determine as well the corona as they influence in vitro/ in vivo behaviors, and
      thus the effect of the protein corona would be rather indirect.

PMID- 30212622
TI  - Deep Insight into PEGylation of Bioadhesive Chitosan Nanoparticles: Sensitivity
      Study for the Key Parameters Through Artificial Neural Network Model.
AB  - Ionically cross-linked chitosan nanoparticles have great potential in
      nanomedicine due to their tunable properties and cationic nature. However, low
      solubility of chitosan severely limits their potential clinical translation.
      PEGylation is a well-known method to increase solubility of chitosan and chitosan
      nanoparticles in neutral media; however, effect of PEG chain length and
      chitosan/PEG ratio on particle size and zeta potential of nanoparticles are not
      known. This study presents a systematic analysis of the effect of PEG chain
      length and chitosan/PEG ratio on size and zeta potential of nanoparticles. We
      prepared PEGylated chitosan chains prior to the nanoparticle synthesis with
      different PEG chain lengths and chitosan/PEG ratios. To precisely estimate the
      influence of critical parameters on size and zeta potential of nanoparticles, we
      both developed an artificial neural network (ANN) model and performed
      experimental characterization using the three independent input variables: (i)
      PEG chain length, (ii) chitosan/PEG ratio, and (iii) pH of solution. We studied
      the influence of PEG chain lengths of 2, 5, and 10 kDa and three different
      chitosan/PEG ratios (25 mg chitosan to 4, 12, and 20 MUmoles of PEG) for the
      synthesis of chitosan nanoparticles within the pH range of 6.0-7.4. Artificial
      neural networks is a modeling tool used in nanomedicine to optimize and estimate
      inherent properties of the system. Inherent properties of a nanoparticle system
      such as size and zeta potential can be estimated based on previous experiment
      results, thus, nanoparticles with desired properties can be obtained using an
      ANN. With the ANN model, we were able to predict the size and zeta potential of
      nanoparticles under different experimental conditions and further confirmed the
      cell-nanoparticle adhesion behavior through experiments. Nanoparticle groups that
      had higher zeta potentials promoted adhesion of HEK293-T cells to nanoparticle
      coated surfaces in cell culture medium, which was predicted through ANN model
      prior to experiments. Overall, this study comprehensively presents the PEGylation
      of chitosan, synthesis of PEGylated chitosan nanoparticles, utilizes ANN model as
      a tool to predict important properties such as size and zeta potential, and
      further captures the adhesion behavior of cells on surfaces prepared with these
      engineered nanoparticles.

PMID- 30212623
TI  - Study of Electrical Stimulation with Different Electric-Field Intensities in the
      Regulation of the Differentiation of PC12 Cells.
AB  - The strategy of using electrical stimulation (ES) to promote the neural
      differentiation and regeneration of injured nerves is proven feasible. Study of
      the possible molecular mechanisms in relation to this ES promotion effect should
      be helpful for understanding the phenomenon. In this study, it was identified
      that the neuronal differentiation of PC12 cells was enhanced when the electric
      field intensity was in the range of 30-80 mV/mm, and a lower or higher electric
      field intensity displayed inferior effects. Under ES, however, levels of
      intracellular reactive oxygen species (ROS), intracellular Ca2+ dynamics, and
      expression of TREK-1 were measured as being gradually increasing alongside higher
      electric-field intensity. In trying to understand the relationship between the ES
      enhancement on differentiation and these variations in cell activities, parallel
      experiments were conducted by introducing exogeneous H2O2 into culture systems at
      different concentrations. Similarly, the effects of H2O2 concentration on the
      neuronal differentiation of PC12 cells, intracellular ROS and Ca2+ levels, and
      TREK-1 expression were systematically characterized. In comparative studies, it
      was found in two cases that ES of 50 mV/mm for 2 h/day and H2O2 of 5 MUM in
      culture medium shared comparable results for intracellular ROS and Ca2+ levels
      and TREK-1 expression. Higher H2O2 concentrations (e.g., 10 and 20 MUM)
      demonstrated adverse effects on cell differentiation and caused DNA damage. A
      stronger ES (e.g., 100 mV/mm), being associated with a higher intracellular ROS
      level, also resulted in weaker enhancement of the neuronal differentiation of
      PC12 cells. These facts suggested that the intracellular ROS generated under ES
      might be an intermediate signal transducer involved in cascade reactions relative
      to cell differentiation.

PMID- 30212624
TI  - Structural Diversity in White-Light-Emitting Hybrid Lead Bromide Perovskites.
AB  - Hybrid organic-inorganic halide perovskites are under intense investigations
      because of their astounding physical properties and promises for optoelectronics.
      Lead bromide and chloride perovskites exhibit intrinsic white-light emission
      believed to arise from self-trapped excitons (STEs). Here, we report a series of
      new structurally diverse hybrid lead bromide perovskites that have broad-band
      emission at room temperature. They feature Pb/Br structures which vary from 1D
      face-sharing structures to 3D corner- and edge-sharing structures. Through single
      crystal X-ray diffraction and low-frequency Raman spectroscopy, we have
      identified the local distortion level of the octahedral environments of Pb2+
      within the structures. The band gaps of these compounds range from 2.92 to 3.50
      eV, following the trend of "corner-sharing < edge-sharing < face-sharing".
      Density functional theory calculations suggest that the electronic structure is
      highly dependent on the connectivity mode of the PbBr6 octahedra, where the edge-
      and corner-sharing 1D structure of (2,6-dmpz)3Pb2Br10 exhibits more disperse
      bands and smaller band gap (2.49 eV) than the face-sharing 1D structure of
      (hep)PbBr3 (3.10 eV). Using photoemission spectroscopy, we measured the energies
      of the valence band of these compounds and found them to remain almost constant,
      while the energy of conduction bands varies. Temperature-dependent PL
      measurements reveal that the 2D and 3D compounds have narrower PL emission at low
      temperature (~5 K), whereas the 1D compounds have both free exciton emission and
      STE emission. The 1D compound (2,6-dmpz)3Pb2Br10 has the highest
      photoluminescence quantum yield of 12%, owing to its unique structure that allows
      efficient charge carrier relaxation and light emission.

PMID- 30212625
TI  - Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related
      Peptidase 6 with On-Target Cellular Activity.
AB  - Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs
      to the family of tissue kallikreins (KLKs). Many KLKs are investigated as
      potential biomarkers for cancer as well as therapeutic drug targets for a number
      of pathologies. KLK6, in particular, has been implicated in neurodegenerative
      diseases and cancer, but target validation has been hampered by a lack of
      selective inhibitors. This work introduces a class of depsipeptidic KLK6
      inhibitors, discovered via high-throughput screening, which were found to
      function as substrate mimics that transiently acylate the catalytic serine of
      KLK6. Detailed structure-activity relationship studies, aided by in silico
      modeling, uncovered strict structural requirements for potency, stability, and
      acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good
      selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular
      assay. Moreover, DKFZ-633, an inhibitor-derived activity-based probe, could be
      used to pull down active endogenous KLK6.

PMID- 30212626
TI  - Rational Design of a LiNbO3-like Nonlinear Optical Crystal, Li2ZrTeO6, with High
      Laser-Damage Threshold and Wide Mid-IR Transparency Window.
AB  - With existing and emerging technologies urgently demanding the expansion of the
      laser wavelengths, high-performance nonlinear optical (NLO) crystals are becoming
      indispensable. Here, a prospective NLO crystal, Li2ZrTeO6, is rationally designed
      by the element substitution of Nb for Zr and Te from LiNbO3, which has been
      recognized as one of the most commercial NLO crystals. Li2ZrTeO6 with R3 symmetry
      inherits the structural merits of LiNbO3 (space group R3 c) and thus meets the
      requirements for NLO applications, including noncentrosymmetric crystal
      structure, moderate birefringence, and phase-matchability. Moreover, it can be
      exploited to achieve more outstanding optical damage resistant behavior (>1.3 GW
      cm-2), exceeding 22 times that of LiNbO3, which is more suitable for high-energy
      laser applications. Notably, this compound displays the widest IR absorption edge
      (7.4 MUm) among all of the noncentrosymmetric tellurates reported so far. These
      excellent attributes suggest that Li2ZrTeO6 is a promising candidate for
      providing high NLO performance. The substitution of Nb for Zr and Te from LiNbO3
      demonstrates a viable strategy toward the rational design of NLO crystals with
      anticipated properties.

PMID- 30212627
TI  - Unphysical Discontinuities in GW Methods.
AB  - We report unphysical irregularities and discontinuities in some key
      experimentally measurable quantities computed within the GW approximation of many
      body perturbation theory applied to molecular systems. In particular, we show
      that the solution obtained with partially self-consistent GW schemes depends on
      the algorithm one uses to self-consistently solve the quasiparticle (QP)
      equation. The main observation of the present study is that each branch of the
      self-energy is associated with a distinct QP solution and that each switch
      between solutions implies a significant discontinuity in the quasiparticle energy
      as a function of the internuclear distance. Moreover, we clearly observe "ripple"
      effects, i.e., when a discontinuity in one of the QP energies induces (smaller)
      discontinuities in the other QP energies. Going from one branch to another
      implies a transfer of weight between two solutions of the QP equation. The cases
      of occupied, virtual, and frontier orbitals are separately discussed on distinct
      diatomics. In particular, we show that multisolution behavior in frontier
      orbitals is more likely if the HOMO-LUMO gap is small.

PMID- 30212628
TI  - Biomimetic Cascade Network between Interactive Multicompartments Organized by
      Enzyme-Loaded Silica Nanoreactors.
AB  - Physical separation of reactions by interactive multicompartments in biological
      cells is an attractive motif to design efficient microreactors that create
      biomimetic cascade reactions. We present an aqueous compartment with three
      different subcompartments that comprise of silica nanoreactors with encapsulated
      enzymes, namely, beta-glucosidase, glucose oxidase, and peroxidase, providing a
      model cascade reaction in confinement. The encapsulated enzymes retain their
      activity as the substrate can reach the active site and the silica shell further
      protects the enzymes from external stresses, such as heat and proteolytic
      degradation. We demonstrate the biomimetic cascade reaction in between the
      compartments ("organelles") inside of an additional microconfinement (water-in
      oil emulsion). This strategy will allow us to design efficient
      multicompartmentalized reactors for further biological and organic reactions.

PMID- 30212629
TI  - Accelerated Construction of Kinetic Network Model of Biomolecules Using Steered
      Molecular Dynamics.
AB  - A new class of rare event acceleration techniques based on steered molecular
      dynamics (SMD) simulations is introduced. A stretching force applied on a
      biomolecule causes it to access large end-to-end distances. Under these
      conditions the biomolecule undergoes rapid conformational changes that are rare
      at zero-force conditions. A theory describing kinetics of a biomolecule at
      various stretching forces is presented. Using the theory, a master-Markov state
      model (master-MSM) is constructed from rates frequently accessed over a small
      range of force conditions. The master-MSM is shown to be applicable over a wide
      range of force conditions. We demonstrate application of the theory to three
      different biomolecular systems, namely, deca-alanine, TBA (thrombin binding
      aptamer), and a RNA hairpin. The master-MSM is used to estimate the kinetics at
      zero-force conditions, i.e., on the unbiased free-energy landscape, resulting
      inasmuch as 2-6 orders-of-magnitude speed-up over standard molecular dynamics.

PMID- 30212630
TI  - Ruthenium-Catalyzed C-H Allylation of Alkenes with Allyl Alcohols via C-H Bond
      Activation in Aqueous Solution.
AB  - A robust Ru(II)-catalyzed C-H allylation of electron-deficient alkenes with allyl
      alcohols in aqueous solution is reported. This method provides a straightforward
      and efficient access to the synthetically useful 1,4-diene skeletons. With the
      assistance of the N-methoxycarbamoyl directing group, this allylation reaction
      features a broad substrate scope with good functional group tolerance, excellent
      regio- and stereoselectivity, absence of metal oxidants, water-tolerant solvents,
      and mild reaction conditions. The mechanistic studies indicate that the process
      of the reversible C-H bond ruthenation is assisted by acetate, and the rate
      determining step is unlikely to be the step of C-H bond cleavage.

PMID- 30212631
TI  - Water Interactions with Hydrophobic versus Hydrophilic Nanosilica.
AB  - It is well-known that interaction of hydrophobic powders with water is weak, and
      upon mixing, they typically form separated phases. Preparation of hydrophobic
      nanosilica AM1 with a relatively large content of bound water with no formation
      of separated phases was the aim of this study. Unmodified nanosilica A-300 and
      initial AM1 (A-300 completely hydrophobized by dimethyldichlorosilane), compacted
      A-300 (cA-300), and compacted AM1 (cAM1) containing 50-58 wt % of bound water
      were studied using low-temperature 1H NMR spectroscopy, thermogravimetry,
      infrared spectroscopy, microscopy, small-angle X-ray scattering, nitrogen
      adsorption, and theoretical modeling. After mechanical activation (~20 atm) upon
      stirring of AM1/water mixture at the degree of hydration h = 1.0 or 1.4 g of
      distilled water per gram of dry silica, all water is bound and the blend has the
      bulk density of 0.7 g/cm3. The temperature and interfacial behaviors of bound
      water depend strongly on a dispersion media type (air, chloroform, and chloroform
      with trifluoroacetic acid (4:1)) because the boundary area between immiscible
      water and chloroform should be minimal. Water and chloroform molecules are of
      different sizes affecting their distribution in pores (voids between silica
      nanoparticles in their aggregates) of different sizes. Structural, morphological,
      and textural characteristics of silicas, and environmental features affect not
      only the distribution of bound water, but also the amounts of strongly (frozen at
      T < 260 K) and weakly (frozen at 260 K < T < 273 K) bound and strongly (chemical
      shift deltaH = 4-6 ppm) and weakly (deltaH = 1-2 ppm) associated waters. Despite
      the changes in the characteristics of cAM1, it demonstrates a flotation effect.
      The developed system with cAM1/bound water could be of interest from a practical
      point of view due to controlled interactions with aqueous surroundings.

PMID- 30212632
TI  - Tracking Ultrafast Bond Dissociation Dynamics at 0.1 A Resolution by Femtosecond
      Extreme Ultraviolet Absorption Spectroscopy.
AB  - Visualizing the real-time dissociation of chemical bonds represents a challenge
      in the study of ultrafast molecular dynamics due to the simultaneous need for sub
      angstrom spatial and femtosecond temporal resolution. Here, we follow the C-I
      dissociation dynamics of strong-field-ionized 2-iodopropane (2-C3H7I) with
      femtosecond extreme ultraviolet (XUV) absorption spectroscopy. By probing the
      iodine 4 d core-level absorption, we resolve a continuous XUV spectral shift on
      the sub-100 fs time scale that accompanies the dissociation of the 2-C3H7I+ spin
      orbit-excited 2 E1/2 state to yield atomic I in the 2 P3/2 state. In combination
      with ab initio calculations of the C-I distance-dependent XUV transition energy,
      we reconstruct the temporal evolution of the C-I distance from the Franck-Condon
      region to the asymptotic region with 10 fs and 0.1 A resolution. The C-I bond
      elongation appears to couple to coherent vibrational motion along the HC(CH3)2
      umbrella mode of the 2-C3H7+ fragment, whose effect on the I 4 d XUV transition
      even at C-I distances of 3.5 A points to the long-range nature of XUV absorption
      probing. Our results suggest that femtosecond XUV absorption spectroscopy, in
      combination with ab initio simulations of XUV transition energies, can be used to
      resolve the ultrafast structural dynamics of large polyatomic molecules.

PMID- 30212633
TI  - Efflux Pump Substrates Shuttled to Cytosolic or Vesicular Compartments Exhibit
      Different Permeability in a Quantitative Human Blood-Brain Barrier Model.
AB  - Representative in vitro blood-brain barrier (BBB) models can support the
      development of strategies to efficiently deliver therapeutic drugs to the brain
      by aiding the characterization of their internalization, trafficking, and
      subsequent transport across the BBB. A collagen type I (COL1) hydrogel-based in
      vitro BBB model was developed to enable the simultaneous characterization of drug
      transport and intracellular processing using confocal microscopy, in a way that
      traditional insert-based in vitro BBB models cannot. Human induced pluripotent
      stem cells (hiPSCs) were differentiated into cells that exhibited a BBB-like
      phenotype on COL1 hydrogels, which included the expression of key BBB-specific
      proteins and low permeability of representative small and large molecule
      therapeutics. Furthermore, the BBB phenotype observed on the COL1 hydrogel was
      similar to that previously reported on porous inserts. The intracellular
      visualization of two small molecule efflux pump substrates within the hiPSC
      derived BBB-like cells demonstrated a difference in cytosolic and vesicular
      accumulation, which complemented permeability measurements demonstrating a
      difference in transport rate. The easy-to-construct COL1-based hiPSC-derived BBB
      model presented here is the first in vitro two-dimensional BBB experimental
      system that enables the simultaneous quantification of cellular permeability and
      visualization of intracellular processes by utilizing confocal microscopy, which
      can provide insights regarding the relationship between transport and
      intracellular trafficking of therapeutic drugs.

PMID- 30212634
TI  - Regio- and Stereodivergent Allylic Reductions of Bicyclic Piperidine Enecarbamate
      Derivatives.
AB  - The particular nature of tetrahydropyrido[4,3- e]-1,4,2-dioxazines of type 1
      allows the regio- and stereoselective obtainment of substituted N-carbamoyl
      tetrahydropyridines by common reducing agents. A completely novel, biologically
      active, bicyclic 1,3-diaza-4-oxa-[3.3.1]-nonene scaffold can be generated by the
      use of lithium triethylborohydride through unprecedented cascade syn-SN2'
      reduction/carbamate reduction/cyclization reactions. The remarkable
      regioselectivity switches in the allylic reduction process have been rationalized
      with the aid of computational studies.

PMID- 30212635
TI  - Intracellular Delivery of Human Purine Nucleoside Phosphorylase by Engineered
      Diphtheria Toxin Rescues Function in Target Cells.
AB  - Despite a wealth of potential applications inside target cells, protein-based
      therapeutics are largely limited to extracellular targets due to the inability of
      proteins to readily cross biological membranes and enter the cytosol. Bacterial
      toxins, which deliver a cytotoxic enzyme into cells as part of their intoxication
      mechanism, hold great potential as platforms for delivering therapeutic protein
      cargo into cells. Diphtheria toxin (DT) has been shown to be capable of
      delivering an array of model proteins of varying sizes, structures, and
      stabilities into mammalian cells as amino-terminal fusions. Here, seeking to
      expand the utility of DT as a delivery vector, we asked whether an active human
      enzyme, purine nucleoside phosphorylase (PNP), could be delivered by DT into
      cells to rescue PNP deficiency. Using a series of biochemical and cellular
      readouts, we demonstrate that PNP is efficiently delivered into target cells in a
      receptor- and translocation-dependent manner. In patient-derived PNP-deficient
      lymphocytes and pluripotent stem cell-differentiated neurons, we show that human
      PNP is efficiently translocated into target cells by DT, where it is able to
      restore intracellular hypoxanthine levels. Further, through replacement of the
      native receptor-binding moiety of DT with single-chain variable fragments that
      were selected to bind mouse HBEGF, we show that PNP can be retargeted into mouse
      splenocytes from PNP-deficient mice, resulting in restoration of the
      proliferative capacity of T-cells. These findings highlight the versatility of
      the DT delivery platform and provide an attractive approach for the delivery of
      PNP as well as other cytosolic enzymes implicated in disease.

PMID- 30212636
TI  - Contact Interaction of Two Oil Lenses Floating on Surface of Deionized Water.
AB  - Droplets on the surface of liquid play an important role in a variety of areas,
      including the petroleum industry, pollution control, and environmental processes.
      In this work, we study the contact interaction between two floating oil lenses on
      the surface of immiscible water. The contact interaction between the two floating
      oil lenses can be divided into three different regimes: (a) the collision
      involving deformation for low-viscous oils, (b) the direct coalescence for high
      viscous oils, and (c) the coexistence (noncoalescence) of oil lenses at
      relatively high temperatures. The temperature dependence of the coalescence time
      for the coalescence of two silicone-oil lenses of large viscosities follows the
      Arrhenius equation.

PMID- 30212637
TI  - Switching to normal diet reverses kwashiorkor-induced salivary impairments via
      increased nitric oxide level and expression of aquaporin 5 in the submandibular
      glands of male Wistar rats.
AB  - Kwashiorkor, a form of malnutrition has been shown to cause impaired salivary
      secretion. However, there is dearth of information on mechanism that underlies
      this complication. Also, whether returning to normal-diet after kwashiorkor will
      reverse these complications or not is yet to be discerned. Thus, this study aimed
      at assessing the mechanisms that underlie kwashiorkor-induced salivary
      impairments and to evaluate the effects of switching back to normal-diet on
      kwashiorkor-induced salivary impairments. Weaning rats were randomly divided into
      3 groups (control, kwashiorkor, re-fed kwashiorkor) of 7 rats each. The control
      had standard rat-chow while the kwashiorkor group (KG) and re-fed kwashiorkor
      group (RKG) were fed 2% protein-diet for 6 weeks to induce kwashiorkor. The RKG
      had their diet changed to standard rat-chow for another 6 weeks. Blood and
      stimulated saliva samples were collected for the analysis of total protein,
      electrolytes, amylase, IgA secretion rate, leptin and ghrelin. Tissue total
      protein, nitric oxide level, expressions of Na+/K+-ATPase, muscarinic (M3)
      receptor and aquaporin5 in the submandibular glands were also determined. Data
      were presented as mean +/- SEM and compared using ANOVA with Tukey's post-hoc
      test. RKG showed improved salivary function evidenced by reduced salivary lag
      time, potassium, with increased, flow rate, sodium, amylase, IgA secretion rate,
      leptin, submandibular nitric oxide level and aquaporin5 expression compared with
      KG. This study for the first time has demonstrated that kwashiorkor caused
      significant reduction in salivary secretion through reduction of nitric oxide
      level and aquaporin5 expression in submandibular salivary glands. Normal-diet re
      feeding after kwashiorkor returned salivary secretion to normal.

PMID- 30212638
TI  - UK newspaper reporting of the NHS cancer drugs fund, 2010 to 2015: a
      retrospective media analysis.
AB  - Objective We wished to explore how UK national newspapers had covered the
      creation and operation of the Cancer Drugs Fund from 2010 to 2015. This was
      introduced to provide cancer patients in England with access to drugs not
      appraised or approved by the National Institute for health and Care Excellence.
      Design We sought stories in nine newspapers from the Factiva database, and copied
      their salient details to a spreadsheet. They were categorised by whether they
      were supportive or critical of the Cancer Drugs Fund and their main arguments,
      which drugs they mentioned and for which cancers. Settings Not applicable
      Participants Not applicable Main outcome results Press coverage was mainly very
      positive, arguing for the Cancer Drugs Fund's extension to Scotland and Wales,
      and a bigger budget, but neglecting the lack of patient benefit and the severe
      side effects that sometimes occurred. Leading this support was the Daily Mail,
      whose influence (measured by the product of number of stories and the paper's
      circulation) was almost greater than that of the other newspapers combined.
      Results Press coverage was mainly very positive, arguing for the Cancer Drugs
      Fund's extension to Scotland and Wales, and a bigger budget, but neglecting the
      lack of patient benefits and the severe side effects that sometimes occurred.
      Leading this support was the Daily Mail, whose influence (measured by the product
      of number of stories and the paper's circulation) was almost greater than that of
      the other newspapers combined. Conclusions Although there was some critical
      analysis of the Cancer Drugs Fund, our analysis shows that most press coverage
      was largely positive and unrepresentative in comparison with the lack of overall
      benefits to patients and society. It is likely that it contributed to the Cancer
      Drugs Fund's continuation despite mounting evidence of its ineffectiveness.

PMID- 30212639
TI  - Deletion of oxyR in Legionella pneumophila causes growth defect on agar.
AB  - The intracellular pathogen Legionella pneumophila (Lp) is a strict aerobe,
      surviving and replicating in environments where it frequently encounters reactive
      oxygen species (ROS), such as the nutrient-poor water environment and its
      replicative niche inside host cells. In many proteobacteria, the LysR-type
      regulator OxyR controls the oxidative stress response; however, the importance of
      the OxyR homologue in Lp is still unclear. Therefore, we undertook the
      characterization of phenotypes associated with the deletion of oxyR in Lp.
      Contrary to the wild type, the oxyR deletion mutant exhibits a severe growth
      defect on charcoal - yeast extract (CYE) agar lacking alpha-ketoglutarate
      supplementation. Growth in AYE broth (CYE without agar and charcoal), in amoeba
      and in human cultured macrophages, and survival in water is unaffected by the
      deletion. Supplementing CYE agar with antioxidants that neutralize ROS or
      introducing the oxyR gene in trans rescues the observed growth defect. Moreover,
      the mutant grows as well as the wild type on CYE plates made with agarose instead
      of agar, suggesting that a compound present in the latter is responsible for the
      growth defect phenotype.

PMID- 30212640
TI  - Paths into Sepsis: Trajectories of Pre-Sepsis Healthcare Use.
AB  - RATIONALE: Sepsis is a leading cause of death and disability whose heterogeneity
      is often cited as a key impediment to translational progress. OBJECTIVE: To test
      the hypothesis that there are consequential and significant differences in sepsis
      outcomes that result from differences in a patient's clinical course leading up
      to sepsis hospitalization. METHODS: Observational cohort study of US Health and
      Retirement Study (HRS) participants in Medicare (1998-2012); US Veterans Affairs
      (VA) beneficiaries (2009). Using latent profile analysis, we identified patient
      sub-types based on trajectory of pre-sepsis healthcare facility use. Subtypes
      were identified in the derivation cohort (1,512 sepsis hospitalizations among
      earlier HRS participants), then validated in two additional cohorts (1,992 sepsis
      hospitalizations among later HRS participants; 32,525 sepsis hospitalizations
      among VA beneficiaries). We measured the association between pre-sepsis path and
      90-day mortality, using chi-square tests and multivariable logistic regression.
      RESULTS: We identified 3 subtypes: "low use" of inpatient healthcare facilities,
      84% of derivation cohort; "rising use"; 12%; and "high use"; 4%. The shape and
      distribution of pre-sepsis trajectories were similar in all three cohorts. In the
      derivation cohort, 90-day mortality differed by pre-sepsis trajectory: 38% (low
      use), 63% (rising use), and 48% (high use), p<0.001. This association persisted
      in the validation cohorts, p<0.001 for each. The rising use class remained an
      independent predictor of mortality after adjustment for potential confounders,
      including detailed physiologic data. CONCLUSIONS: In national cohorts of sepsis
      patients, we have shown that several distinct paths into sepsis exist. These
      paths, identified from trajectories of pre-sepsis healthcare use, are predictive
      of 90-day mortality.

PMID- 30212641
TI  - Determining the impact of an interprofessional learning in practice model on
      learners and patients.
AB  - The Institute of Medicine recently expressed a need to measure the impact of
      interprofessional education (IPE) on health professions collaborative behavior in
      practice environments and patient outcomes, and the National Center for
      Interprofessional Practice and Education has focused research efforts to connect
      interprofessional practice and education. We describe a model intentionally
      designed to link interprofessional practice experience in ambulatory care setting
      and an IPE curriculum for students, called the Interprofessional Learning in
      Practice (ILIP) model. The study objective was to determine the impact of the
      ILIP model on student and patient outcomes during a 24-month intervention period.
      Student satisfaction was collected through a brief survey administered post-ILIP
      model. Patient outcomes were collected from before and after the intervention
      period through a retrospective chart review of patients who received care through
      the ILIP model. For the study, disease indicators for the top three chronic
      diagnoses of depression, hypertension, and type 2 diabetes mellitus were chosen
      as the patient outcomes. Student outcomes were analyzed using descriptive
      statistics and the Mann-Whitney U test. Patient outcomes were analyzed using
      McNemar's test and paired t-tests. Of the 382 students who participated in the
      ILIP model during the study period, 179 completed surveys, indicating that they
      valued the experience, valued learning from interprofessional preceptors, and
      gained interprofessional skills to use in their future practice. During the 24
      month intervention, 401 patients were evaluated post-ILIP model, statistically
      significant results demonstrated HbA1c values for patients with diabetes were
      reduced by 0.5% and depression screening improved from 9% to 91%. Additionally,
      patients' hypertension control was similar to baseline and diabetes control (as
      defined as HbA1c <=8%) was improved compared to baseline but did not reach
      statistical significance. By aligning interprofessional practice and education in
      the ILIP model, students had a positive experience, gained interprofessional
      collaboration skills, and provided value-added benefits to improve patient
      outcomes.

PMID- 30212642
TI  - A Chemical Time Machine for Mucosal Healing.
AB  - Mucosal healing regenerates the mucosal complex upon injury. Mucosal repair
      requires sequential biologic steps paradoxically enabled or blocked by
      prostaglandin E2. In this issue of Cell Host & Microbe, Jain et al. (2018) find
      that the microbial metabolite, deoxycholate, regulates prostaglandin E2 and thus
      coordinates the steps of mucosal healing.

PMID- 30212643
TI  - NLRP12: The Monarch of the Gut.
AB  - Innate pattern recognition receptors have been implicated in the obesity
      associated imbalance of gut microbiota. In this issue of Cell Host & Microbe,
      Truax et al. (2018) report that NLRP12 prevents high-fat-diet-induced obesity by
      maintaining beneficial short-chain fatty acid-producing microbiota.

PMID- 30212644
TI  - Blocking the Exit: CHIKV Neutralizing Antibodies Nip Viral Egress in the Bud.
AB  - Neutralizing antibody responses are critical for protection from virus-induced
      disease. In this issue of Cell Host & Microbe, Jin et al. (2018) use advanced
      microscopy to elucidate mechanisms by which anti-CHIKV neutralizing monoclonal
      antibodies block viral egress and activate ADCC, suggesting such antibodies may
      be "triply functional."

PMID- 30212645
TI  - Mycobacterium tuberculosis Joyrides Alveolar Macrophages into the Pulmonary
      Interstitium.
AB  - Alveolar macrophages reside in the airway lumen, where they are thought to
      remain. However, in this issue of Cell Host & Microbe,Cohen et al. (2018) show
      that Mycobacterium tuberculosis may induce their translocation into the lung
      interstitium, potentially acting as a Trojan horse for bacillary dissemination to
      other phagocytes.

PMID- 30212646
TI  - With Probiotics, Resistance Is Not Always Futile.
AB  - Probiotics and other bacteriotherapies are actively being explored and applied as
      symptom- and disease-modifying agents. In a recent issue of Cell, two papers
      contribute to our understanding of how live bacterial therapies variably affect
      individuals and the short- and longer-term impact of these therapies on
      colonization and host response.

PMID- 30212647
TI  - Breathe Soft, What Bugs through Early Windows Break?
AB  - In this issue of Cell Host & Microbe, Teo et al. (2018) explore the development
      of the upper airway microbiota over the first 5 years of life and provide
      evidence for a "critical window" of microbial exposure that contributes to
      chronic wheezing, a precursor to asthma.

PMID- 30212648
TI  - Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic
      Bacteria and Allergy in Childhood Respiratory Disease.
AB  - Repeated cycles of infection-associated lower airway inflammation drive the
      pathogenesis of persistent wheezing disease in children. In this study, the
      occurrence of acute respiratory tract illnesses (ARIs) and the nasopharyngeal
      microbiome (NPM) were characterized in 244 infants through their first five years
      of life. Through this analysis, we demonstrate that >80% of infectious events
      involve viral pathogens, but are accompanied by a shift in the NPM toward
      dominance by a small range of pathogenic bacterial genera. Unexpectedly, this
      change frequently precedes the detection of viral pathogens and acute symptoms.
      Colonization of illness-associated bacteria coupled with early allergic
      sensitization is associated with persistent wheeze in school-aged children, which
      is the hallmark of the asthma phenotype. In contrast, these bacterial genera are
      associated with "transient wheeze" that resolves after age 3 years in non
      sensitized children. Thus, to complement early allergic sensitization, monitoring
      NPM composition may enable early detection and intervention in high-risk
      children.

PMID- 30212649
TI  - The Inhibitory Innate Immune Sensor NLRP12 Maintains a Threshold against Obesity
      by Regulating Gut Microbiota Homeostasis.
AB  - In addition to high-fat diet (HFD) and inactivity, inflammation and microbiota
      composition contribute to obesity. Inhibitory immune receptors, such as NLRP12,
      dampen inflammation and are important for resolving inflammation, but their role
      in obesity is unknown. We show that obesity in humans correlates with reduced
      expression of adipose tissue NLRP12. Similarly, Nlrp12-/- mice show increased
      weight gain, adipose deposition, blood glucose, NF-kappaB/MAPK activation, and M1
      macrophage polarization. Additionally, NLRP12 is required to mitigate HFD-induced
      inflammasome activation. Co-housing with wild-type animals, antibiotic treatment,
      or germ-free condition was sufficient to restrain inflammation, obesity, and
      insulin tolerance in Nlrp12-/- mice, implicating the microbiota. HFD-fed Nlrp12-/
      mice display dysbiosis marked by increased obesity-associated
      Erysipelotrichaceae, but reduced Lachnospiraceae family and the associated
      enzymes required for short-chain fatty acid (SCFA) synthesis. Lachnospiraceae or
      SCFA administration attenuates obesity, inflammation, and dysbiosis. These
      findings reveal that Nlrp12 reduces HFD-induced obesity by maintaining beneficial
      microbiota.

PMID- 30212651
TI  - The Legionella Effector Kinase LegK7 Hijacks the Host Hippo Pathway to Promote
      Infection.
AB  - The intracellular pathogen Legionella pneumophila encodes translocated effector
      proteins that modify host cell processes to support bacterial survival and
      growth. Here, we show that the L. pneumophila effector protein LegK7 hijacks the
      conserved Hippo signaling pathway by molecularly mimicking host Hippo kinase
      (MST1 in mammals), which is the key regulator of pathway activation. LegK7, like
      Hippo/MST1, phosphorylates the scaffolding protein MOB1, which triggers a
      signaling cascade resulting in the degradation of the transcriptional regulators
      TAZ and YAP1. Transcriptome analysis revealed that LegK7-mediated targeting of
      TAZ and YAP1 alters the transcriptional profile of mammalian macrophages, a key
      cellular target of L. pneumophila infection. Specifically, genes targeted by the
      transcription factor PPARgamma, which is regulated by TAZ, displayed altered
      expression, and continuous interference with PPARgamma activity rendered
      macrophages less permissive to L. pneumophila intracellular growth. Thus, a
      conserved L. pneumophila effector kinase exploits the Hippo pathway to promote
      bacterial growth and infection.

PMID- 30212652
TI  - Non-linguistic effects of language switching training.
AB  - What is the relationship between bilingual language control (BLC) mechanisms and
      domain-general executive control (EC) processes? Do these two domains share some
      of their mechanisms? Here, we take a novel approach to this question,
      investigating whether short-term language switching training improves non
      linguistic task switching performance. Two groups of bilinguals were assigned to
      two different protocols; one group was trained in language switching (switching
      task training group) another group was trained in blocked language picture naming
      (single-block training group). Both groups performed a non-linguistic and
      linguistic switching task before (pre-training) and after training (post
      training). Non-linguistic and linguistic switch costs decreased to a greater
      extent for the switching-task training than for the single-block training group
      from pre- to post-training. In contrast, mixing costs showed similar reductions
      for both groups. This suggests short-term language switching training can
      transfer to the non-linguistic domain for certain sub-mechanisms (i.e., switch
      cost). Thus, there is some overlap of the control mechanisms across domains.

PMID- 30212650
TI  - The MAP4 Kinase SIK1 Ensures Robust Extracellular ROS Burst and Antibacterial
      Immunity in Plants.
AB  - Microbial patterns are recognized by cell-surface receptors to initiate pattern
      triggered immunity (PTI) in plants. Receptor-like cytoplasmic kinases (RLCKs),
      such as BIK1, and calcium-dependent protein kinases (CPKs) are engaged during PTI
      to activate the NADPH oxidase RBOHD for reactive oxygen species (ROS) production.
      It is unknown whether protein kinases besides CPKs and RLCKs participate in RBOHD
      regulation. We screened mutants in all ten Arabidopsis MAP4 kinases (MAP4Ks) and
      identified the conserved MAP4K SIK1 as a positive regulator of PTI. sik1 mutants
      were compromised in their ability to elicit the ROS burst in response to
      microbial features and exhibited compromised PTI to bacterial infection. SIK1
      directly interacts with, phosphorylates, and stabilizes BIK1 in a kinase activity
      dependent manner. Furthermore, SIK1 directly interacts with and phosphorylates
      RBOHD upon flagellin perception. Thus, SIK1 positively regulates immunity by
      stabilizing BIK1 and activating RBOHD to promote the extracellular ROS burst.

PMID- 30212653
TI  - Gestalt similarity groupings are not constructed in parallel.
AB  - Our visual system organizes spatially distinct areas with similar features into
      perceptual groups. To better understand the underlying mechanism of grouping, one
      route is to study its capacity and temporal progression. Intuitively, that
      capacity seems unlimited, and the temporal progression feels immediate. In
      contrast, here we show that in a visual search task that requires similarity
      grouping, search performance is consistent with serial processing of those
      groups. This was true across several experiments, for seeking a single ungrouped
      pair among grouped pairs, vice versa, and for displays with tiny spacings between
      the grouped items. In a control condition that ruled out display complexity
      confounds, when the small inter-object spacing was removed so that that pairs
      touched, removing the need to group by similarity, search became parallel. Why is
      similarity grouping so slow to develop? We argue that similarity grouping is
      'just' feature selection - seeing a red, bright, or square group is global
      selection of those features. This account predicts serial processing of one
      feature group at a time, and makes new falsifiable predictions about how
      properties of feature-based selection should be reflected in similarity grouping.

PMID- 30212654
TI  - Women's perceived barriers to giving birth in health facilities in rural Kenya: A
      qualitative evidence synthesis.
AB  - BACKGROUND: In Kenya, uptake of skilled care during birth remains lower in rural
      areas when compared to urban areas, despite efforts by the government to
      encourage facility-based births by abolishing maternity fees in public health
      facilities. OBJECTIVE: To synthesise published and unpublished qualitative
      research that explores women's perceived barriers to facility-based birth in
      rural Kenya. DESIGN: Qualitative evidence synthesis DATA SOURCES: Multiple
      electronic databases (MEDLINE, EMBASE, PsycINFO, POPLINE, CINAHL, Web of Science
      and ProQuest), grey literature searches, citation chaining and checking of
      reference lists. REVIEW METHODS: Studies were screened by title, abstract and
      full text, after which a standardised qualitative checklist was used to assess
      study quality. Synthesis of extracted data followed the 'best-fit' framework
      method, enhanced with a pathway-based model for the improvement of maternal and
      newborn care. RESULTS: Sixteen eligible studies were identified. Key themes were:
      (i) knowledge, attitudes and practices, including past experiences of health
      facilities and community beliefs about facility services; (ii) insufficient
      demand for professional care caused by the perceived advantages of seeking
      alternative care during birth and the disadvantages of facility-based births;
      (iii) limited access to services, especially in rural areas, because of poor
      infrastructure; (iv) misconceptions regarding labour characteristics and, (v)
      poor awareness of labour outcomes. CONCLUSIONS: Important factors can be
      characterised as 'push' factors (those pushing women away from facilities) and
      'pull' factors (those related to the relative advantage of facility-based
      births). However, key to an individual woman's decision are factors relating to
      knowledge, attitudes and practices and awareness of labour outcomes. While a
      critical tension exists between government policy and consumer choice, the
      prevalence of inadequate awareness and the dominance of past experiences and
      community beliefs offer significant obstacles to a woman in making an informed
      choice about her preferred place of giving birth.

PMID- 30212655
TI  - Chemotherapy based combinations in AML: Time to take a step back?

PMID- 30212656
TI  - Co2P@NiCo2O4 bi-functional electrocatalyst with low overpotential for water
      splitting in wide range pH electrolytes.
AB  - The Co2P@NiCo2O4 bi-functional electrocatalyst was fabricated for hydrogen
      evolution reaction and oxygen evolution reaction in acidic, neutral and alkaline
      media. The Co2P@NiCo2O4 in alkaline media exhibites an extremely low
      overpotential of 170 mV in oxygen evolution to achieve a current density of 10 mA
      cm-2 and produces stable water splitting nearly 30 h. The anchored-Co2P can
      enhance the electrochemical performance of pristine NiCo2O4 as well as increase
      the tolerance in acidic media of NiCo2O4. Additional, the Co2P is oxidized to
      oxides/hydroxides species during the electrocatalytic reaction, which acts as the
      active centers of the electrocatalysis. The Co2P@NiCo2O4 catalyst can be used as
      an effective bifunctional synergistic center in a wide range of pH values (from 0
      to 14).

PMID- 30212657
TI  - The performance of surfactant mixtures at low temperatures.
AB  - Optimising detergency at lower temperatures is of increasing interest due to
      environmental and economic factors, and requires a greater understanding of the
      effects of temperature on the adsorption of surfactant mixtures at interfaces.
      The adsorption properties of surfactant mixtures and biosurfactant/surfactant
      mixtures have been studied at room temperatures and at temperatures below ambient
      using surface tension and neutron reflectivity measurements. For the ternary
      surfactant mixture of octaethylene monododecyl ether, C12E8, sodium dodecyl 6
      benzene sulfonate, LAS, and sodium dioxyethylene glycol monododecyl sulfate,
      SLES, the surface tension at the air-water interface increases with decreasing
      temperature. In contrast, there is a notable reduction in the increase in the
      surface tension with a decrease in temperature from 25  degrees C to 10  degrees
      C for the 5 component rhamnolipid/surfactant mixture of the mono-rhamnose, R1,
      and di-rhamnose, R2, with C12E8/LAS/SLES. The associated neutron reflectivity
      data for the ternary C12E8/LAS/SLES mixture and the significant observation is
      that the 3, 4, and 5-component mixtures containing rhamnolipids in conjunction
      with the other surfactants show changes in composition and adsorbed amounts of
      the individual components which are close to the experimental error. However the
      significant observation is that the neutron reflectivity data indicate that the
      improved surface tension tolerance at lower temperatures is associated with the
      dominance of the rhamnolipid adsorption in such mixtures. Hence the introduction
      of the rhamnolipids provides a tolerance to the adverse effects associated with
      reduced temperatures, and a potential for improved detergency at relatively low
      temperatures.

PMID- 30212658
TI  - Combined drought and virus infection trigger aspects of respiratory metabolism
      related to grapevine physiological responses.
AB  - In the Mediterranean region, grapevines usually deal with drought during their
      summer growth season. Concurrently, grapevines are hosts to a large number of
      viruses from which grapevine leafroll associated virus-3 is one of the most
      widespread and provokes considerable economic losses in many vineyards. However,
      information concerning grapevine metabolic responses to the combination of
      drought and viral infection is scarce. Gas-chromatography coupled to mass
      spectrometry based metabolite profiling was used in combination with growth
      analysis, viral loads and gas exchange data to perform an integrative study of
      the effects of individual and combined stress in two Majorcan grapevine varieties
      at two experimental years. Metabolic responses of both varieties to the
      combination of water stress and virus infection were specific and not predicted
      from the sum of single stress responses. Correlations between respiration,
      biomass and key metabolites highlight specific adjustments of respiratory and
      amino acid metabolism possibly underlying the maintenance of carbon balance and
      growth in grapevines under stress combination.

PMID- 30212659
TI  - Functional analysis of tomato rhamnogalacturonan lyase gene Solyc11g011300 during
      fruit development and ripening.
AB  - Rhamnogalacturonan I (RG-I) is a domain of plant cell wall pectin. The
      rhamnogalacturonan lyase (RGL) enzyme (EC 4.2.2.23) degrades RG-I by cleaving the
      alpha-1,4 glycosidic bonds located between the l-rhamnose and d-galacturonic
      residues of the main chain. While RGL's biochemical mode of action is well known,
      its effects on plant physiology remain unclear. To investigate the role of the
      RGL enzyme in plants, we have expressed the Solyc11g011300 gene under a
      constitutive promoter (CaMV35S) in tomato cv. 'Ohio 8245' and evaluated the
      expression of this and other RGL genes, enzymatic activity and alterations in
      vegetative tissue, and tomato physiology in transformed lines compared to the
      positive control (plants harboring the pCAMBIA2301 vector) and the isogenic line.
      The highest expression levels of the Solyc11g011300, Solyc04g076630, and
      Solyc04g076660 genes were observed in leaves and roots and at 10 and 20 days
      after anthesis (DAA). Transgenic lines exhibited lower RGL activity in leaves and
      roots and during fruit ripening, whereas higher activity was observed at 10, 20,
      and 30 DAA than in the isogenic line and positive control. Both transgenic lines
      showed a lower number of seeds and fruits, higher root length, and less pollen
      germination percentage and viability. In red ripe tomatoes, transgenic fruits
      showed greater firmness, longer shelf life, and reduced shriveling than did the
      isogenic line. Additionally, a delay of one week in fruit ripening in transgenic
      fruits was also recorded. Altogether, our data demonstrate that the
      Solyc11g011300 gene participates in pollen tube germination, fruit firmness, and
      the fruit senescence phenomena that impact postharvest shelf life.

PMID- 30212660
TI  - The establishment of a shared care plan as it is experienced by elderly people
      and their next of kin: A qualitative study.
AB  - One strategy to achieve coordination of care for older people with complex care
      needs is the establishment of shared care plans. The aim of this study was to
      explore the process of establishing a shared care plan from the perspective of
      elderly people and their next of kin. Data were collected via 12 semi-structured
      interviews with 12 older persons targeted in joint care planning and 11 next of
      kin, either alone or together. The analysis was conducted using content analysis.
      The results reflect the process of establishing a shared care plan in the three
      categories; Preparation, Content and Results with belonging sub-categories.
      Preparation showed that the possibility to influence the preparation of the joint
      care plan meeting was sometimes limited and the purpose was not always clear. The
      Content category showed that the meeting was sometimes experienced as an
      unstructured, general conversation or focused on practical matters. And Results
      of the process were shown to be successful in terms of having positive effects or
      fulfilling needs, but also sometimes as being pointless. Thus, the results show
      that the process of establishing a shared care plan is somewhat unclear to the
      older person and their next of kin and that they are rarely involved in the
      decisions regarding when and if a shared care plan is needed. If joint care
      planning is expected to serve as a tool to accomplish a more person-centred care,
      then the person must be regarded as an equal partner all throughout the decision
      making and planning process.

PMID- 30212661
TI  - Forensic age determination of human inflicted porcine bruises inflicted within 10
      h prior to slaughter by application of gene expression signatures.
AB  - Prediction-models based on gene expression profiles from experimental bruises are
      capable of determining the age of bruises with a precision of +/-2 h. However,
      these models have not yet been applied on tissue from pigs in forensic cases
      requested by the police. We applied two prediction-models, based on mRNA
      expression of 13 (prediction-model no. 1) and 4 genes (prediction-model no. 2)
      involved in inflammation, on forensic cases of porcine bruises in order to
      determine if gene expression profiles can be used for age determination in
      forensic cases. Subcutaneous fat tissue from bruises notified to the police was
      sampled: 1) within 6 h after slaughter (group no. I, n = 142), and 2) after
      freezing the skin for up to 1 year (group no. II, n = 40). qPCR of genes involved
      in inflammation was performed to predict the bruise age after partial least
      squares analysis. mRNA expression data were obtained for 52.8% and 7.5% bruises
      in group nos. I and II, respectively. Prediction-model no. 2, based on the mRNA
      expression of Selectin E, Selectin P, Interleukin 6 and Nuclear Factor Kappa Beta
      Subunit1, was most suitable for predicting the age of bruises within 8 h prior to
      slaughter. In conclusion, mRNA expression profiles can assist in estimating the
      age of bruises. However, when applying gene expression signatures in forensic
      cases the age estimate should be interpreted together with histological
      manifestations. Subcutaneous tissue must be stabilized hours after the bruises
      are detected in order to obtain mRNA of a sufficient quality.

PMID- 30212662
TI  - Reply to Dr. Ueshima: The relationship of local anesthetic volume and dermatomal
      spread of sensorial block in erector spinae plane blocks: A new dilemma.

PMID- 30212663
TI  - A comparative study of different aspects in manipulating ratio spectra used for
      the analysis of cefradine in the presence of its alkaline degradation product.
AB  - Six stability-indicating UV-spectrophotometric methods manipulating ratio spectra
      were utilized for the analysis of cefradine in presence of its alkaline
      degradate. These methods are different forms of transformations; ratio
      difference, mean centering, derivative ratio using numerical differentiation,
      derivative ratio using Savitsky-Golay filter, continuous wavelet transform and
      derivative continuous wavelet transform. Water was used as a solvent and the
      linearity ranges were 6-26 MUg/mL. Determination of accuracy and precision for
      the suggested procedures were executed. Assessment of specificity was run through
      analyzing laboratory prepared mixtures containing cefradine and its alkaline
      degradate. The suggested methods were useful for cefradine estimation in tablets.
      Statistically, the outputs obtained from the recommended and published methods
      reveal no significant differences.

PMID- 30212664
TI  - New fluorescent chemosensors based on mononuclear copper complex for highly
      selective and sensitive detection of phosphate anion in aqueous solution and
      living cells.
AB  - Three new probes, named, [Cu(L1)2]Cl2 (C1), [Cu(L2)2]Cl2 (C2) and [Cu(L3)2]Cl2
      (C3) were synthesized and well characterized. The probes C1, C2 and C3 were
      successfully achieved for the efficient detection of PO43- as turn-on
      fluorescence chemosensors in DMSO/H2O (v:v = 2:8, Tris-HCl pH = 7.20). The limit
      of detection (LOD) of probes C1, C2 or C3 for PO43- could be as low as 0.029 MUM,
      0.048 MUM, 0.079 MUM, respectively, which were effectively applied for the
      determination of the PO43- concentration in environmental water of swimming pool.
      What's more, the binding constant between probes C1, C2, C3 and PO43- are
      estimated to be 3.11 * 107 M-1 (R2 = 0.9992), 1.84 * 107 M-1 (R2 = 0.9956), 1.93
      * 107 M-1 (R2 = 0.9976), respectively. The proposed mechanism for the "on-off-on"
      fluorescence response was confirmed by ESI-MS and fluorescence spectrum.
      Moreover, the membrane-permeable probe C1 was successfully demonstrated in
      monitoring of PO43- in cultured HepG2 cells.

PMID- 30212665
TI  - Design and validation of a universal influenza virus enrichment probe set and its
      utility in deep sequence analysis of primary cloacal swab surveillance samples of
      wild birds.
AB  - Influenza virus infections in humans and animals are major public health
      concerns. In the current study, a set of universal influenza enrichment probes
      was developed to increase the sensitivity of sequence-based virus detection and
      characterization for all influenza viruses. This universal influenza enrichment
      probe set contains 46,953 120nt RNA biotin-labeled probes designed based on all
      available influenza viral sequences and it can be used to enrich for influenza
      sequences without prior knowledge of type or subtype. Marked enrichment was
      demonstrated in influenza A/H1N1, influenza B, and H1-to-H16 hemagglutinin
      plasmids spiked into human DNA and in cultured influenza A/H2N1 virus.
      Furthermore, enrichment effects and mixed influenza A virus infections were
      revealed in wild bird cloacal swab samples. Therefore, this universal influenza
      virus enrichment probe system can capture and enrich influenza viral sequences
      selectively and effectively in different samples, especially ones with degraded
      RNA or containing low amount of influenza RNA.

PMID- 30212666
TI  - Clinical implications and electrochemical biosensing of monoamine
      neurotransmitters in body fluids, in vitro, in vivo, and ex vivo models.
AB  - Monoamine neurotransmitters (MNTs) belong to one of the most important groups of
      neurotransmitters in the central nervous system. They play crucial role in
      functioning of cardiovascular, renal, and hormonal systems along with
      establishing human brain-body integration. Abnormal level of MNT is associated
      with numerous psychotic (schizophrenia, depression, dementia, etc.) and
      neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's disease,
      etc.), therefore their sensitive and robust detection is of great clinical
      significance. Electrochemical detection (ECD) techniques have been paving the
      path in this direction, for more than four decades now. Keeping the immense
      importance of MNTs in mind, this review has been formulated to describe
      fundamentals of MNTs followed by their clinical significance in neuroscience.
      Herein, we have emphasized on the ECD of MNTs, in various matrices reported till
      date. In order to provide information on ECD of MNTs in clinically comparable
      systems, we have included a comprehensive discussion on sensor design and its
      analytical performance towards analyzing MNTs in the in vitro, in vivo, and ex
      vivo models. An extensive table is also incorporated to provide better
      understanding of the role of MNTs in various clinical conditions. Furthermore,
      this review briefly discusses the challenges faced with EC sensing techniques and
      loopholes present in current research works. Apart from this, three extended
      tables are also included in this review, to provide an insight into the amount of
      work done in ECD of MNTs in last ten years (2008-2018). These tables
      comprehensively discuss sensor fabrication strategies for determining MNTs in
      various matrices and models along with their mode of detection and analytical
      performance.

PMID- 30212667
TI  - Sensitive detection of telomerase activity in cancer cells using portable pH
      meter as readout.
AB  - This study developed a portable and sensitive biosensor for the detection of
      telomerase activity extracted from HeLa cells by monitoring urease regulated pH
      change. In the presence of telomerase, the telomerase substrate (TS) primer was
      elongated by adding telomeric repeats (TTAGGG)n firstly. The TS primer was then
      immobilized onto streptavidin magnesphere paramagnetic particles (PMPs). The
      elongated repeat unit can hybridize with biotinylated complementary DNA (cDNA) to
      specifically capture biotinylated urease onto PMPs. After magnetic separation,
      the PMPs complex was mixed with urea solution. As urease can catalyze the
      hydrolysis of urea into ammonia and induce pH increasing of the solution, the
      activity of telomerase can be detected by pH-sensitive dyes or by a portable pH
      meter easily. The changed pH has a linear relationship with the logarithm of the
      number of HeLa cells from 50 to 10,000 and with a detection limit of ~20 HeLa
      cells, which indicated the proposed method have potential application in
      telomerase-related cancer diagnosis.

PMID- 30212668
TI  - Socioeconomic determinants of China's growing CH4 emissions.
AB  - Reducing CH4 emissions is a major global challenge, owing to the world-wide rise
      in emissions and concentration of CH4 in the atmosphere, especially in the past
      decade. China has been the greatest contributor to global anthropogenic CH4
      emissions for a long time, but current understanding towards its growing
      emissions is insufficient. This paper aims to link China's CH4 emissions during
      2005-2012 to their socioeconomic determinants by combining input-output models
      with structural decomposition analysis from both the consumption and income
      perspectives. Results show that changes in household consumption and income were
      the leading drivers of the CH4 growth in China, while changes in efficiency
      remained the strongest factor offsetting CH4 emissions. After 2007, with the
      global financial crisis and economic stimulus plans, embodied emissions from
      exports plunged but those from capital formation increased rapidly. The enabled
      emissions in employee compensation increased steadily over time, whereas
      emissions induced from firms' net surplus decreased gradually, reflecting the
      reform on income distribution. In addition, at the sectoral level, consumption
      and capital formation respectively were the greatest drivers of embodied CH4
      emission changes from agriculture and manufacturing, while employee compensation
      largely determined the enabled emission changes across all industrial sectors.
      The growth of CH4 emissions in China was profoundly affected by the macroeconomic
      situation and the changes of economic structure. Examining economic drivers of
      anthropogenic CH4 emissions can help formulate comprehensive mitigation policies
      and actions associated with economic production, supply and consumption.

PMID- 30212669
TI  - Biodiesel production as a solution to waste cooking oil (WCO) disposal. Will any
      type of WCO do for a transesterification process? A quality assessment.
AB  - Biodiesel production can be the solution to the problem of how to deal with waste
      cooking oils (WCO) and the associated problem of environmental contamination.
      Every year, tonnes of WCO are poured into toilets and drains, contaminating water
      supplies and creating serious problems in waste water treatment plants. WCO is a
      waste material that can be used to produce biodiesel. The main aim of this study
      is to determine how the type of WCO (and how much it has been used) affect the
      quality of the biodiesel obtained. Four types of WCO (sunflower, maize, olive and
      a blend of soybean, palm and sunflower) with two different levels of degradation
      were used to produce biodiesel. The WCO were subjected to a transesterification
      process, using NaOH and methanol as reagents, reaction temperatures of between 50
      and 67.5  degrees C, a 60 min reaction time and magnetic stirring. The quality of
      the biodiesel that was obtained was measured on the basis of four parameters as
      set out in the UNE-EN 14214 standard: density at 15  degrees C, kinematic
      viscosity at 40  degrees C, acid number and iodine value. This characterisation
      forms part of the second aim of this research, namely to determine which types of
      WCO can produce a quality biodiesel via a single stage transesterification
      process. The results show that the biodiesel quality is closely related to that
      of the WCO, and that the transesterification method can be recommended for WCO
      with densities (at 15  degrees C) of up to 930 kg/m3, kinematic viscosity (at 40 
      degrees C) of up to 38.46 mm2/s, and acid numbers of up to 4.19 mg KOH/g. The
      production method used is a simple, economic and effective way of adding value to
      a hazardous and difficult to manage waste material like WCO.

PMID- 30212670
TI  - Optimization of aluminium recovery from water treatment sludge using Response
      Surface Methodology.
AB  - For decades, water treatment plants in Malaysia have widely employed aluminium
      based coagulant for the removal of colloidal particles in surface water. This
      generates huge amount of by-product, known as sludge that is either reused for
      land applications or disposed to landfills. As sludge contains high concentration
      of aluminium, both can pose severe environmental issues. Therefore, this study
      explored the potential to recover aluminium from water treatment sludge using
      acid leaching process. The evaluation of aluminium recovery efficiency was
      conducted in two phases. The first phase used the one factor at a time (OFAT)
      approach to study the effects of acid concentration, solid to liquid ratio,
      temperature and heating time. Meanwhile, second phase emphasized on the
      optimization of aluminium recovery using Response Surface Methodology (RSM). OFAT
      results indicated that aluminium recovery increased with the rising temperature
      and heating time. Acid concentration and solid to liquid ratio, however, showed
      an initial increment followed by reduction of recovery with increasing
      concentration and ratio. Due to the solidification of sludge when acid
      concentration exceeded 4 M, this variable was fixed in the optimization study.
      RSM predicted that aluminium recovery can achieve 70.3% at optimal values of 4 M,
      20.9%, 90  degrees C and 4.4 h of acid concentration, solid to liquid ratio,
      temperature and heating time, respectively. Experimental validation demonstrated
      a recovery of 68.8 +/- 0.3%. The small discrepancy of 2.2 +/- 0.4% between
      predicted and validated recovery suggests that RSM was a suitable tool in
      optimizing aluminium recovery conditions for water treatment sludge.

PMID- 30212671
TI  - Simultaneous boron (B) removal and electricity generation from domestic
      wastewater using duckweed-based wastewater treatment reactors coupled with
      microbial fuel cell.
AB  - Boron removal from water environment is a critical issue for scientific spotlight
      because its removal from wastewater is difficult and costly with conventional
      treatment method. Herein, an innovative, cost effective and attractive method
      which depends on duckweed-based wastewater treatment systems coupled with
      microbial fuel cell reactor (DWWT-MFC) was investigated for B-polluted domestic
      wastewater treatment and simultaneous electricity generation for the first time
      in an eco-technological study. Lemna gibba L. was selected as a model duckweed
      species, and different reactors were also designed to identify which mechanisms
      are dominant for B removal in a DWWT-MFC reactor matrix. DWWT-MFC reactor
      achieved 71% B removal in experiment period, and the plant effect on B removal
      mechanisms in the reactor matrix was recorded as 37.7 +/- 4.92% (F = 2.543, p <
      0.05). However, supplementary aeration and microbial effects on B removal were
      determined as negligible. Average maximum voltage output was found as 1.47 V, and
      maximum power density was 34.8 mW/m2 at a current density of 43.9 mA/m2 with
      supplementary aeration. Moreover, DWWT-MFC reactor achieved 84%, 81% and 76% of
      COD, NH4+ and PO43- removal efficiencies, respectively. Moreover, L. gibba grew
      well in the anode chamber of DWWT-MFC with an average biomass yield of 218 +/- 43
      g/m2 and a total chlorophyll (a+b) concentration of 30.2 mg g-1, which indicates
      that anolyte environment was not toxic for L. gibba growth. Consequently, it can
      be suggested that environmental experts may use DWWT-MFC as an efficient removal
      method to treat B from domestic wastewater and to produce bioelectricity.

PMID- 30212672
TI  - Degradation of organic pollutants by photoelectro-peroxone/ZVI process:
      Synergistic, kinetic and feasibility studies.
AB  - In this study a novel hybrid process was employed for the degradation of Metanil
      Yellow (MY). The operational parameters of photoelectro-peroxone/zero valent iron
      (PEP/ZVI) process were studied and the complete decoloration was found at pH =
      3.0, 100 mg/L ZVI, 33.2 mg/L ozone, 300 mA applied current and 25 min reaction
      time. The combination of UV, ozone, electrogenerated H2O2 and ZVI showed high
      synergistic effect for MY degradation. ZVI showed high reusability in PEP/ZVI
      process. Among anions, nitrite ion demonstrated high inhibitory effect while
      chloride ions had no significant effect on MY degradation. Scavenging tests
      depicted that hydroxyl radical and singlet oxygen were the main agents of MY
      degradation. PEP/ZVI process was tested for several emerging pollutants
      (benzotriazole, 4-chlorophenol, carmoisine and tetracycline); the results
      presented the effectiveness of the process for the degradation of pollutants in a
      way that complete degradation occurred at only 30 min. Moreover, the performance
      of PEP/ZVI was examined for the treatment of two actual wastewaters. PEP/ZVI
      demonstrated an excellent function in terms of the removal of organic compounds
      to achieve discharging standards.

PMID- 30212673
TI  - Carbon Sequestration Anticipation Response to land use change in a mountainous
      karst basin in China.
AB  - The present article reports an assessment of afforestation potential and
      anticipation of carbon sequestration in the Houzhai River Basin in Guizhou
      Province in southwestern China. Total of 2755 soil profiles consisting of 22,057
      soil samples were collected according to a grid-sampling method at a 150 m scale
      in the Houzhai River basin, and the SOC contents in soil samples were analyzed
      using a titration method. General information regarding the geographic
      characteristics of each sampling grid was recorded in the field. The results
      indicate that land use in the Houzhai River Basin is very complex. Land use
      status and land use change in the study area were closely associated with local
      geographic characteristics and variations in economic structures. There were
      approximately 15.26 km2 of land that could or should be rearranged as
      afforestation land in the Houzhai River Basin. The increased SOC storage (0.00
      1.00 m soil horizon) would be up to 5.48 * 104 Mg, 6.42 * 104 Mg, 4.77 * 104 Mg
      and 3.18 * 104 Mg when all of the calculated lands became shrub-grass lands,
      shrub lands, arbor-shrub forest lands and arbor forest lands, respectively. The
      increased SOC percentages would be 52.16%, 61.13%, 45.39% and 30.32%,
      respectively, in comparison with the present SOC storage in these lands.

PMID- 30212674
TI  - Vegetation and soil nutrient restoration of cut slopes using outside soil spray
      seeding in the plateau region of southwestern China.
AB  - Outside soil spray seeding (OSSS) is used widely for road cut revegetation, and
      the artificial soil used in OSSS can improve slope soil conditions and nutrients,
      and help promote plant growth and succession. Three different slopes was
      investigated to evaluate the effectiveness of OSSS for restoration, including a
      natural slope (NS), a cut slope without any artificial recovery treatment (CSW)
      and a cut slope treated with OSSS (CSO). The recovery of cut slopes was
      determined by evaluating a number of factors, including indices associated with
      plants on the slopes, soil enzyme activities (urease and sucrase), and soil
      nutrient content (soil organic matter (SOM), total phosphorous (TP), total
      potassium (TK), available nitrogen (AN), available phosphorous (AP), available
      potassium (AK), potassium (K+), calcium (Ca2+), magnesium (Mg2+), and sulphate
      (SO42-)). The results indicated that the vegetation and soil conditions differed
      between the three slopes. The Shannon-Wiener index (H), the Simpson index (D),
      and the Margalef index (R) values from the CSO and NS were lower than those of
      the CSW, whilst the Pielou index (E) value and vegetation canopy cover were
      higher for the CSO and NS than for the CSW. The content of SOM and AN in soil
      from the CSO was lower than in soil from the NS and CSW, and content of many
      nutrients were higher in soil from the CSO than in soil from the NS and CSW. This
      suggests that the restoration of vegetation and soil nutrients on the CSO was
      relatively successful. Our results indicated that the use of OSSS to restore cut
      slopes is effective in plateau areas. However, despite improvements in soil
      nutrient levels, there were still nutritional imbalances. Therefore, more
      attention should be paid to balancing nutrients in the later stage of OSSS
      implementation for the recovery of cut slopes at high altitudes.

PMID- 30212675
TI  - Phosphorus retention along a typical urban landscape river with a series of
      rubber dams.
AB  - Small dams are widely constructed in urban rivers as landscape engineering
      practice, which increasingly cause eutrophication problems. Phosphorus retention
      in dammed rivers is a critical factor driving eutrophication, but it is little
      known in urban landscape river systems controlled by small dams. In this study,
      we investigated the retention of different phosphorus species along an urban
      landscape river with 30 rubber dams. We found that 42.5% (7.69 metric tons/yr) of
      the total phosphorus (TP) was trapped within dams, of which total particulate
      phosphorus (TPP) retention load accounted for 81.5%. From first river segment BBF
      4# to the segments further downstream, the TP retention rate sharply decreased
      from 47.6% to -8.3%-9.2%, and phosphorus was mainly retained in the uppermost
      segment of the dammed river. The retention rate of dissolved reactive phosphorus
      (86.3%) was higher than that of TPP (40.3%) because of biological uptake.
      Further, with a retention rate of -11.3%, the dammed river was a net source of
      dissolved organic phosphorus. Different hydrological regimes, due to seasonal
      events and dam management, greatly influenced phosphorus retention within the
      dammed river, resulting in higher retention loads in the rainy season than in the
      dry season, and very low retention loads in the snowmelt season, with 1.48, 0.55
      and 0.06 t/month, respectively. Our findings imply that management practices
      should focus on reducing the phosphorus export from the upper watershed and
      improving the hydrodynamic conditions of the dammed urban landscape river with
      regard to eutrophication.

PMID- 30212676
TI  - Terrestrial humic-like fluorescence peak of chromophoric dissolved organic matter
      as a new potential indicator tracing the antibiotics in typical polluted
      watershed.
AB  - Natural surface waters are threatened globally by antibiotics pollution. In this
      study, we analyzed antibiotics and CDOM (Chromophoric dissolved organic matter)
      fluorescence in different water bodies using HPLC method and Excitation Emission
      Matrix- Parallel factor analysis, respectively. A combination of field studies in
      the Yinma River Watershed were conducted in rivers, reservoirs and urban rivers,
      and 65 CDOM and antibiotic samples were taken in April, May, July, and August
      2016. EEM-PARAFAC analysis identified two components; a humic-like (C1) component
      and a tryptophan-like (C2) component. The redundancy analysis (RDA) demonstrated
      that CDOM could explain 38.2% (two axes) of the five antibiotics in reservoirs (N
      = 31), and 26.0% (two axes) of those in rivers and urban water (N = 30).
      Furthermore, the Pearson correlation coefficient between Sulfamethoxazole and C1
      in reservoir water was 0.91 (t-test, 2-tailed, p < 0.01), and that between
      Sulfamethoxazole and C2 was 0.68 (t-test, 2-tailed, p < 0.01). This indicated
      that the humic-like component of CDOM PARAFAC fluorescence could detect
      Sulfamethoxazole contamination levels in the homogenized reservoir waters. Our
      results identified Sulfamethoxazole and Quinolones (Norfloxacin, 16.5 ng L-1;
      Enrofloxacin, 0.3 ng L-1; Ciprofloxacin, 30.9 ng L-1) at mean concentrations of
      369.5 ng L-1 and 15.9 ng L-1, respectively, which were the higher levels in
      natural surface waters. The FTIR spectroscopy of the mixture of humic acid and
      sulfamethoxazole showed that the absorbance at 3415 cm-1 linked to OH stretching
      of OH groups and at 1386 cm-1 because of OH bending and vibration of COOH groups
      became weaker, indicating that COOH groups of humic acid can adsorb and react
      with -NH2 of sulfamethoxazole. The CDOM PARAFAC components can be adapted for
      online or in situ fluorescence measurements as an early warning of
      Sulfamethoxazole distribution and contamination in similar aquatic environments.

PMID- 30212677
TI  - Efficiency of wastewater treatment facilities: The influence of scale economies.
AB  - The water cycle, from catchment to discharge, is a sector that involves an
      important investment and operation and maintenance costs. In particular, sewage
      treatment is a challenge for governments because they are having to consider
      economic, environmental, and social aspects. Within the European Union,
      implementation of Directive 91/271/EEC is responsible for the location of
      wastewater treatment facilities in the territory, due to the requirement that all
      urban areas must have this infrastructure to reduce the environmental impact of
      treated water in water bodies. Different sizes of municipalities affect the
      design of each wastewater treatment plant (WWTP) and cause variations in the
      operation process. The presence of scale economies in this sector has a
      significant influence on the efficiency of the wastewater treatment process and
      has a direct impact on the operational costs. Based on the pursuit of economic
      and environmental efficiency, this analysis extends the scope of the current
      literature because it recommends a specific, population equivalent (p.e.) range
      for which it would be suitable to achieve efficiency in wastewater treatment
      facilities-shedding light on the open debate about scale economies in WWTPs.

PMID- 30212678
TI  - Study on cellulose microfilaments based composite spheres: Microwave-assisted
      synthesis, characterization, and application in pollutant removal.
AB  - A novel study of synthesizing the temperature-responsive polymer grafted
      cellulose filaments/Poly (N-isopropylacrylamide) (NIPAM) spheres (P-MCCBs) was
      carried out for the removal of dyes and heavy metal ions. The novelty of the
      presented work consists of the application of the nano-sized pore-forming agent
      (Calcium Carbonate) and the introduction of a temperature-responsive monomer
      (NIPAM) while preparing the adsorbents. In addition, the spherical adsorbents
      were synthesized through an in-situ free radical polymerization using a microwave
      assisted heating approach. The morphology, chemical structure, pH, and thermal
      sensitivity of P-MCCBs were characterized properly. The adsorption and desorption
      behaviors of dyes and heavy metal ions on P-MCCBs were also investigated. The
      results showed that P-MCCBs exhibited a fast adsorption rate, the adsorption
      equilibrium reached within 80 min and 40 min for MB and Pb2+, respectively (25 
      degrees C). Moreover, around 5-8% and 20% of adsorbed MB and Pb2+ were released
      at the temperature above 45  degrees C. The adsorption kinetics followed pseudo
      second-order model, and the desorption process was fit well using Higuchi and
      Korsmeyer-Peppas models. These results indicated that P-MCCBs could be served as
      a novel material for controllable adsorption and desorption processes of various
      contaminants.

PMID- 30212679
TI  - Blended pulp mill, forest humus and mine residual material Technosols for mine
      reclamation: A growth-chamber study to explore the role of physiochemical
      properties of substrates and microbial inoculation on plant growth.
AB  - A growth chamber trial was conducted to investigate the effects of blends of pulp
      and paper mill residuals and forest humus on soil properties, microbial
      communities and germination rate and biomass production of annual ryegrass
      (Lolium multiflorum) in both acid-producing and neutral to mildly alkaline mine
      tailings in a mine reclamation context. The organic residual amendments improved
      the nutritional status of the tailings substrates, and increased pH in acid
      generating tailings, leading to higher germination rates and improved plant
      growth. A trace addition (<0.02% of sludge by dry weight) of natural forest floor
      material as a microbial inoculum to the sludge could increase plant biomass up to
      four-fold. The effects of sludge application on bioavailability of metals were
      variable, with the concentration of soluble copper (Cu) and nickel (Ni)
      increasing in some of the substrates following organic amendments. Addition of
      paper mill residuals to mine tailings modified the microbial communities observed
      in the oligotrophic tailings with the majority of DNA sequences in the sludge
      amended substrates being found to be closely related to heterotrophic bacterial
      species rather than the chemolithotrophic communities that dominate tailings
      environments.

PMID- 30212680
TI  - Use of proton pump inhibitors and risk of ischemic events in the general
      population.
AB  - BACKGROUND AND AIMS: A potential increased risk of cardiovascular events has been
      suggested for proton pump inhibitors (PPIs), the most commonly prescribed drugs
      for the management of upper gastrointestinal disorders. We aimed to estimate the
      risk of hospitalization for cardio/cerebrovascular (CV) events in a cohort of
      incident PPI users. METHODS: A nested case-control study was carried out using
      regional healthcare utilization databases. For each case (hospitalization for non
      haemorrhagic CV event), up-to-five controls randomly selected from the cohort
      were matched by gender, age at cohort entry, and index date. Exposure was
      estimated as recency of therapy (current, recent and past users) and number of
      days covered. Adjusted conditional logistic regression was used to estimate the
      association between exposure and outcome. RESULTS: Among new PPI users, we
      identified 17,832 cases and 89,160 controls (males 64.9%; mean age 58.9 years).
      Cases showed a significantly higher prevalence of use of drugs for diabetes,
      hypertension and hypercholesterolemia than controls. Risk of CV events was
      significantly higher for current (OR 1.61; 95%CI 1.55-1.68) and recent users (OR
      1.15; 95%CI 1.06-1.26) compared to past users. Analogous results were found
      stratifying for cardiovascular (ORcurrent 1.71; 95%CI 1.63-1.81) and
      cerebrovascular events (ORcurrent 1.43; 95%CI 1.34-1.54). The increased risk was
      confirmed in subgroups by antithrombotic, statin use, or exposure duration. The
      same analysis for H2-antagonists use showed no significant results. CONCLUSIONS:
      In primary care setting, PPI use was independently associated with increased risk
      of first-time cardiovascular event, consistent with the evidence that PPIs
      adversely impact vascular function, underlying the need to promote appropriate
      prescribing of these drugs.

PMID- 30212681
TI  - Comparison of angiotensin-converting enzyme inhibitors and angiotensin II
      receptor blockers in patients with diabetes mellitus and non-ST-segment elevation
      myocardial infarction who underwent successful percutaneous coronary
      intervention.
AB  - BACKGROUND AND AIMS: Angiotensin-converting-enzyme inhibitors (ACEI) and
      angiotensin II receptor blockers (ARB) are known to be beneficial for either non
      ST-segment elevation myocardial infarction (NSTEMI) patients or diabetes mellitus
      (DM) patients. However, the comparative efficacy of ACEI versus ARB in patients
      with NSTEMI and DM is unclear. The aim of this study was to compare the
      protective efficacy of ACEI versus ARB in patients with NSTEMI and DM, who
      underwent percutaneous coronary intervention (PCI) with drug-eluting stents
      (DES). METHODS: Among 53,281 patients enrolled in the nationwide Korea Acute
      Myocardial Infarction Registry, 3426 patients with NSTEMI and DM, who were
      treated with renin-angiotensin system (RAS) inhibitors, had undergone successful
      PCI with DESs. They were classified into two groups: ACEI group (N = 2076), and
      ARB group (N = 1350). Individual major clinical outcomes and major adverse
      cardiac events (MACE), the composite of total death, myocardial infarction (MI),
      and revascularization were compared between the two groups for up to two years.
      RESULTS: After propensity score-matching analysis, two propensity-matched groups
      (1103 pairs, total = 2206) were generated, and the baseline characteristics were
      balanced. Although all causes of death and recurrent MI were not different
      between the two groups, the incidence of revascularization (4.0% vs. 7.1%; p =
      0.002), including target vessel (2.3% vs. 5.0; p = 0.002), and MACE (8.7% vs.
      12.5%, p = 0.008), were lower in the ACEI group than the ARB group at two-year
      follow-up. CONCLUSIONS: Compared with ARB, no beneficial effects of ACEI on all
      causes of death, cardiac death, or recurrence of MI were observed, but ACEI
      reduced the incidence of revascularization and MACE in this population. Thus,
      well-designed trials with a larger population are needed to confirm these
      results.

PMID- 30212682
TI  - Treatment of atherosclerosis by traditional Chinese medicine: Questions and
      quandaries.
AB  - Atherosclerosis and its complications, such as myocardial infarction and stroke,
      are the major causes of morbidity and mortality, and development of effective
      therapies for both prevention and treatment of this disease is critically
      important. Currently, there are many drugs available for atherosclerotic disease,
      but the lipid-lowering drugs statins are still the first-choice for treatment of
      hypercholesterolemia, a major risk factor for atherosclerosis. On the other hand,
      traditional Chinese medicines, mainly Chinese herbal medicines (CHM), have been
      widely used in China and in other Asian countries for the treatment of
      atherosclerotic diseases. Although many CHMs have been reported to be effective
      for treating atherosclerotic diseases for more than two thousand years, there are
      still many difficulties for their use, such as lack of scientific evidence
      assessed by rigorous clinical trials, complicated components and unclear
      pharmacological mechanisms, which often hamper the widespread use of CHMs in
      Western countries. Due to these concerns, CHMs are usually considered as
      complimentary or alternative treatment for atherosclerotic diseases. In this
      review, we provide an overview of the pathophysiology of atherosclerosis viewed
      by Western and traditional Chinese medicine, summarize pros and cons on the
      efficacy of CHMs for atherosclerosis and discuss what is necessary for CHM use to
      spread to Western societies.

PMID- 30212683
TI  - Progranulin in the hematopoietic compartment protects mice from atherosclerosis.
AB  - BACKGROUND AND AIMS: Progranulin is a circulating protein that modulates
      inflammation and is found in atherosclerotic lesions. Here we determined whether
      inflammatory cell-derived progranulin impacts atherosclerosis development.
      METHODS: Ldlr-/- mice were transplanted with bone marrow from wild-type (WT) or
      Grn-/- (progranulin KO) mice (referred to as Tx-WT and Tx-KO, respectively).
      RESULTS: After 10 weeks of high-fat diet feeding, both groups displayed similarly
      elevated plasma levels of cholesterol and triglycerides. Despite abundant
      circulating levels of progranulin, the size of atherosclerotic lesions in Tx-KO
      mice was increased by 47% in aortic roots and by 62% in whole aortas. Aortic root
      lesions in Tx-KO mice had increased macrophage content and larger necrotic cores,
      consistent with more advanced lesions. Progranulin staining was markedly reduced
      in the lesions of Tx-KO mice, indicating little or no uptake of circulating
      progranulin. Mechanistically, cultured progranulin-deficient macrophages
      exhibited increased lysosome-mediated exophagy of aggregated low-density
      lipoproteins resulting in increased cholesterol uptake and foam cell formation.
      CONCLUSIONS: We conclude that hematopoietic progranulin deficiency promotes diet
      induced atherosclerosis in Ldlr-/- mice, possibly due to increased exophagy
      mediated cholesterol uptake. Circulating progranulin was unable to prevent the
      increased lesion development, consistent with the importance of progranulin
      acting via cell-autonomous or local effects.

PMID- 30212684
TI  - Performance, microbial community and fluorescent characteristic of microbial
      products in a solid-phase denitrification biofilm reactor for WWTP effluent
      treatment.
AB  - Microbial products, i.e. extracellular polymeric substance (EPS) and soluble
      microbial product (SMP), have a significant correlation with microbial activity
      of biologically based systems. In present study, the spectral characteristics of
      two kinds of microbial products were comprehensively evaluated in a solid-phase
      denitrification biofilm reactor for WWTP effluent treatment by using poly
      (butylene succinate) (PBS) as carbon source. After the achievement of PBS
      biofilm, nitrate and total nitrogen removal efficiencies were high of 97.39 +/-
      1.24% and 96.38 +/- 1.1%, respectively. The contents of protein and
      polysaccharide were changed different degrees in both LB-EPS and TB-EPS.
      Excitation-emission matrix (EEM) implied that protein-like substances played a
      significant role in the formation of PBS-biofilm. High-throughput sequencing
      result implied that the proportion of denitrifying bacteria, including
      Simplicispira, Dechloromonas, Diaphorobacter, Desulfovibrio, increased to 9.2%,
      7.4%, 4.8% and 3.6% in PBS-biofilm system, respectively. According to EEM
      PARAFAC, two components were identified from SMP samples, including protein-like
      substances for component 1 and humic-like and fulvic acid-like substances for
      component 2, respectively. Moreover, the fluorescent scores of two components
      expressed significant different trends to reaction time. Gas chromatography-mass
      spectrometer (GC-MS) implied that some new organic matters were produced in the
      effluent of SP-DBR due to biopolymer degradation and denitrification processes.
      The results could provide a new insight about the formation and stability of
      solid-phase denitrification PBS-biofilm via the point of microbial products.

PMID- 30212685
TI  - Topsoil application during the rehabilitation of a manganese tailing dam
      increases plant taxonomic, phylogenetic and functional diversity.
AB  - Rehabilitation of tailing dams poses important challenges because sterile
      materials and poor or even toxic soils hinder plant development and the
      regeneration of the pre-mining-activity biota. In this study, we analyzed the
      effectiveness of rehabilitating a 14-year-old manganese tailing dam by comparing
      three different regeneration treatments (topsoil application, seedling plantation
      and spontaneous regeneration) with undisturbed reference sites. We used soil
      chemical composition, taxonomic, functional and phylogenetic diversity and the
      above-ground tree biomass as indicators of rehabilitation success. In terms of
      soil chemical composition, we showed that the seedling and natural regeneration
      treatments were similar to one another but different from the reference sites.
      Topsoil application presented an intermediate chemical composition between the
      reference site and the other two treatments. Moreover, the species richness,
      Shannon diversity index and phylogenetic diversity indicated faster
      rehabilitation of ecosystem biodiversity with the topsoil treatment, although
      levels from reference are not yet achieved. We also observed higher basal area
      and biomass production in the topsoil treatment. However, these patterns were not
      observed for functional diversity, for which no differences among treatments were
      observed. We concluded that topsoil application provided the best results;
      however, we must emphasize that even this approach was not sufficient to
      rehabilitate the system to the similar level of biodiversity found in the
      surrounding ecosystem up to the present.

PMID- 30212686
TI  - A review on agro-industrial waste (AIW) derived adsorbents for water and
      wastewater treatment.
AB  - There is a large amount of studies surrounding the usage of agro-industrial waste
      (AIW) for the adsorptions of organic pollutants (dyes) and inorganic pollutants
      (heavy metals) in water/wastewater. This method is normally treated as an
      alternative approach to the conventional water/wastewater treatment. However,
      there are some increasing interests for investigators to identify novel
      adsorption materials for pollutants removal. It is particularly noteworthy that
      most AIW wastes are not currently used at the original state, but modified in a
      variety of ways to reinforce the porosity and adsorption surface area of the
      material. Nanostructuring, activation, carbonization, and grafting are some
      common modification technologies of agricultural waste adsorbents. Besides, the
      characteristic, preparation and application of adsorbents from various industrial
      wastes, including natural materials and biosorbents, were summarized.
      Additionally, the challenges and perspectives for future researches of waste
      derived adsorbents were studied. This review provides an important insight on
      using AIWs as precursor materials for preparing adsorbents in water/wastewater
      treatment.

PMID- 30212687
TI  - Effect of organic/inorganic nanoparticles on performance of polyurethane
      nanocomposites for potential wound dressing applications.
AB  - This study focuses on the evaluation and modification of polyurethane (PU)
      membranes containing organic and inorganic nanoparticles for potential use as a
      wound dressing. For the purpose of PU nanocomposite preparation, chitosan (CS)
      was converted into nanoparticles by the ionic-gelation method to improve its
      blending capability with the PU matrix. These CS nanoparticles (nano-CS) were
      obtained as a hydrophilic organic filler with different contents and were
      utilized along with inorganic titanium dioxide (TiO2) nanoparticles in the
      nanocomposite membrane preparation. The membranes were prepared using phase
      inversion technique and their microstructure was controlled by manipulating the
      solvent non-solvent exchange rate. Obtained results demonstrate that addition of
      polymer solvent to nonsolvent induced a microstructure alteration from finger
      like to sponge-like, which is more suitable for fluid uptake and consequently
      more useful for wound dressing applications. Similar results were obtained by
      introduction of nanoparticles to membranes. Due to the polar nature of
      nanoparticles and their effects on PU structure, prepared membranes showed 71.5%
      improve in swelling when compared to neat PU. Moreover, the reinforcement effect
      of nanoparticles caused an 18.94% increase in ultimate tensile strength in
      comparison with bare PU film, while elongation at break was not affected
      considerably. In addition, prepared PU nanocomposite films showed suitable
      antibacterial activity of 69% against Staphylococcus aureus and did not show any
      toxicity to human fibroblast cells. Based on these results, simultaneous use of
      TiO2 and chitosan nanoparticles can improve both physical and antibacterial
      properties of PU as an ideal wound dressing.

PMID- 30212688
TI  - Vitamin E-based redox-sensitive salinomycin prodrug-nanosystem with paclitaxel
      loaded for cancer targeted and combined chemotherapy.
AB  - Cancer stem cells (CSCs) can resist conventional chemotherapy to lead to cancer
      recurrence. For complete eradication of cancers, an effective CSCs therapeutic
      strategy should be developed to combine with conventional chemotherapy. In this
      work, a novel vitamin E-based redox-sensitive salinomycin (SAL, an inhibitor for
      CSCs) prodrug nanoparticles (TS NPs) and hyaluronic acid (HA)-coated TS NPs (HTS
      NPs) were fabricated to deliver paclitaxel (PTX) for cancer-targeted and combined
      chemotherapy. Both TS and HTS prodrug NPs had mean diameter of about 200 nm with
      uniform size distribution, excellent drug loading capacity for PTX, and
      glutathione-triggered SAL and PTX release profiles. The HTS prodrug NPs had
      enhanced cellular uptake efficiency over TS NPs due to CD44 receptor-mediated
      endocytosis, hence exerting stronger potency of SAL upon CSCs-enriched
      mammospheres formation and G0/G1 cell phase arresting. Cytotoxicity and 3D tumor
      spheroids assays demonstrated that both TS and HTS prodrug NPs themself can
      synergize with loaded PTX to maximize the chemotherapeutic effect. Obviously, the
      latter demonstrated a more potent anticancer efficacy due to improved
      intracellular drug delivery efficiency. These results suggested that the designed
      TS prodrug NPs, especially the coated HTS NPs can serve as an effective anti-CSCs
      strategy for cancer targeted and combination treatments.

PMID- 30212689
TI  - Physicochemical characterization of solid lipid nanoparticles comprised of
      glycerol monostearate and bile salts.
AB  - Successful applications of solid lipid nanoparticles (SLNs) rely on their
      physicochemical properties which are mainly governed by their comprising
      materials (e.g., lipids, emulsifiers) and preparation methods. We have prepared
      biocompatible solid lipid nanoparticles with glycerol monostearate as lipid and
      varying combinations of bile salts sodium deoxycholate and sodium cholate (bile
      salts to lipid ratio 8% w/w) as emulsifiers. The detailed characterization of
      solid lipid nanoparticles was performed using a combination of light scattering,
      microscopic, calorimetric, and spectroscopic techniques. It was seen that
      different compositions of bile salts yield nanoparticles with different sizes.
      The use of only sodium deoxycholate (8% w/w) produces nanoparticles with average
      sizes ~487 nm. The average particle size increases with increasing cholate
      fraction. A higher average particle size around ~652 nm is obtained with 8% (w/w)
      sodium cholate. All the SLNs show good physical stability at room temperature and
      do not show polymorphic transformation during the storage. In order to study the
      microenvironments, solid lipid nanoparticles are loaded with an external
      fluorescent-probe fisetin (probe to lipid ratio 1% w/w). Photophysical properties
      of fisetin loaded SLNs indicate the micro-heterogenicity inside the
      nanoparticles.

PMID- 30212690
TI  - Burkholderia cepacia immobilized on eucalyptus leaves used to simultaneously
      remove malachite green (MG) and Cr(VI).
AB  - A multifunctional biomaterial capable of simultaneously removing malachite green
      (MG) and Cr(VI) was prepared by immobilizing Burkholderia cepacia (B. cepacia) on
      eucalyptus leaves (EL). The maximum uptake of MG (60 mg/L) and Cr(VI) (20 mg/L)
      were 94.8% and 71.9% respectively, which was more efficient than when using EL or
      free cells alone. SEM-EDS demonstrated that B. cepacia was attached to EL and
      that Cr(VI) was biosorbed into the immobilized cells. FTIR showed that the
      degradation by functional groups of immobilized cells was in keeping with the
      products, detected by GC-MS, which suggested that MG could be degraded to 4
      dimethylamino benzophenone and 4-dimethylamino phenol. The removal of both MG and
      Cr(VI) by EL immobilized cells fit the pseudo-second order adsorption kinetic
      model well (with both R2>0.983). The equilibrium adsorption capacity of MG was
      9.59, 18.67 and 28.64 mg/g for initial MG concentrations of from 30, 60, 90 mg/L,
      respectively when the concentration of Cr(VI) was held constant at 20 mg/L. The
      adsorption capacity of Cr(VI) increased from 3.49, 7.68 to 9.79 mg/g as the
      initial Cr(VI) concentrations increased (10, 20, 30 mg/L) while the MG
      concentration was kept constant at 60 mg/L. The results showed that eucalyptus
      leaves as a low cost and eco-friendly material have some potential to be an
      effective immobilization for environmental applications.

PMID- 30212691
TI  - Cadmium governance in Europe's phosphate fertilizers: Not so fast?
AB  - The European Union has been concerned about cadmium (Cd), because of its toxic
      nature, since the 1970s. While many anthropogenic sources of Cd were regulated
      early on at the community level, and most member states later established
      national limits, Cd content in widely used mineral fertilizers remains
      uncontrolled across the EU. In 1997, the European Commission first suggested
      phased Cd limit values in mineral fertilizers as a promising approach to reducing
      Cd content in soils and harmonising national measures. For over 20 years,
      however, no harmonised measures have been adopted because confusion remains about
      the basis for, and level of, such limits. We comment on the latest deadlock over
      the revision of the Fertilisers Regulation and strengthen assumptions as to why
      such limits are timely, pertinent, and possible.

PMID- 30212692
TI  - The translocation of antimony in soil-rice system with comparisons to arsenic:
      Alleviation of their accumulation in rice by simultaneous use of Fe(II) and NO3.
AB  - Antimony (Sb) accumulation in rice grains is a potential risk to human health.
      This study aims to develop agronomic practices that can reduce the accumulation
      of Sb in rice grain in contaminated soil. A pot culture experiment was conducted
      to investigate the effects of co-application of ferrous iron and nitrate (Fe(II)
      + NO3-) in paddy soils on Sb uptake by rice. The co-application of Fe(II) and NO3
      promoted abiotic/biotic Fe(II) oxidation and mineralization in the rhizosphere
      soil and formation of Fe plaques, consequently, Sb bioavailability was
      significantly reduced by enhancing Sb immobilization on the newly formed Fe(III)
      (hydr)oxides. The results were compared with those for arsenic (As) in the same
      trial and it was shown that the two metalloids have different translocation
      behavior in the soil-rice plant system. The adsorption of Sb, especially the
      Sb(V), on Fe(III) (hydr)oxides was more significantly enhanced by the decreased
      soil pH after the application of Fe(II) + NO3- than that of As. The uptake of Sb
      by the roots of rice was much more difficult but it was much easier to be
      transported from the rice straw to the grains compared to As. The differences
      might be mainly caused by the different uptake mechanisms of Sb and As by rice
      plants from paddies. The bioavailable As(III) would be much more efficient in
      entering into the rice roots than Sb(III) through the aquaporin channel due to
      its much smaller ionic radius; the bioavailable As(V), entering into the rice
      roots via phosphate transporters, would also be more efficient in taking up by
      roots than Sb(V), which pathway from soil to rice roots remains unclear. These
      findings provide new insights into Sb biogeochemical behavior in soil-rice plant
      systems and demonstrate that co-application of Fe(II) and NO3- could be a
      promising strategy for safely-utilizing Sb contaminated sites in the future.

PMID- 30212693
TI  - The pharmaceutical pollutant fluoxetine alters reproductive behaviour in a fish
      independent of predation risk.
AB  - Pharmaceutical pollutants constitute a major threat to wildlife because of their
      capacity to induce biological effects at low doses. One such pollutant is the
      antidepressant fluoxetine, which has been detected in surface waters globally at
      levels that recent studies suggest can alter physiology and behaviour in aquatic
      organisms. However, wildlife exposed to pharmaceutical contaminants are typically
      confronted with multiple stressors simultaneously, including predation risk,
      which is a particularly important natural stressor that can have direct (e.g.
      mortality) and indirect (e.g. changed prey behaviour) fitness effects.
      Accordingly, we investigated potential impacts of environmentally realistic
      fluoxetine exposure on reproductive behaviour in the guppy (Poecilia reticulata)
      under predation risk. Specifically, we tested whether fluoxetine exposure altered
      mating behaviour in male and female guppies in the presence of either a predatory
      spangled perch (Leiopotherapon unicolor) or a non-predatory rainbowfish
      (Melanotaenia splendida) control. We found that fluoxetine and the presence of a
      predatory spangled perch did not interact to affect reproductive behaviour. We
      also found that, independent of a predatory threat, fluoxetine exposure altered
      male mating strategy, with males in the high treatment conducting significantly
      more coercive 'sneak' copulations, whereas the number of courtship displays
      performed was not significantly affected. Moreover, while fluoxetine exposure did
      not significantly affect the amount of time that males and females spent
      following one another, we found that females, but not males, followed a potential
      partner less when in the presence of the predatory fish. Finally, both sexes
      reacted to the risk of predation by spending less time in close proximity to a
      predator than a non-predator. In combination, our findings highlight the capacity
      of fluoxetine to influence processes of sexual selection at field-realistic
      concentrations and emphasise the importance of considering multiple stressors
      when assessing impacts of pharmaceutical pollutants on the behaviour of wildlife.

PMID- 30212694
TI  - Significant reduction in air pollutant emissions from household cooking stoves by
      replacing raw solid fuels with their carbonized products.
AB  - Residential solid fuel combustion contributes significantly to ambient and indoor
      air pollutions. An appropriate clean solid fuel to reduce residential emissions
      is urgently needed. This study evaluates the reduction in pollutant emissions
      achieved by carbonized solid fuels in residential cooking practice. Four biochar
      samples, three semi-coke briquette samples and their raw materials were tested in
      a typical cooking stove. These carbonized samples showed higher thermal
      efficiencies and lower particulate matter (PM) emission factors (EFs) than their
      raw material samples. Owing to distilled volatile matter during carbonization
      treatment, average energy delivered-based PM2.5 EFs were 10 +/- 5 mg/kJ
      (carbonized) and 50 +/- 28 mg/kJ (raw) for the biomass and 0.33 +/- 0.04 mg/kJ
      (carbonized) and 3.0 +/- 1.3 mg/kJ (raw) for the coal samples. The energy
      delivered-based EFs of organic carbon, elemental carbon, and 16 priority
      polycyclic aromatic hydrocarbons extracted from PM2.5 samples from carbonized
      fuels were reduced by 97 +/- 1%, 93 +/- 3%, and 97 +/- 2%, respectively, for the
      tested biomass samples, and those for the tested coal samples were 96 +/- 1%, 90
      +/- 6%, and 98 +/- 2%, respectively. Average EFs of benzo[a]pyrene equivalent
      carcinogenic potency for individual polycyclic aromatic hydrocarbons were reduced
      95 +/- 3% to ~0.51 MUg/kJ (carbonized) from ~19.6 MUg/kJ (raw). Furthermore, the
      average ratio of volatile organic compounds contained in PM2.5 samples was also
      reduced from 38.8 +/- 5.4% to 7.1 +/- 3.9%. These results suggest that carbonized
      solid fuels exhibit better performance in reducing carcinogenic potency and
      pollutants, most of which are highly correlated with the volatile matter content
      of the fuel. Switching from raw solid fuel to carbonized solid fuel will help to
      reduce pollutant emissions from household combustion and achieve both
      environmental benefits and health benefits for household residents.

PMID- 30212695
TI  - Spatial distribution and changes of permafrost on the Qinghai-Tibet Plateau
      revealed by statistical models during the period of 1980 to 2010.
AB  - The Qinghai-Tibet Plateau (QTP), where is underlain by the highest and most
      extensive mid-altitude permafrost, is undergoing more dramatic climatic warming
      than its surrounding regions. Mapping the distribution of permafrost is of great
      importance to assess the impacts of permafrost changes on the regional climate
      system. In this study, we applied logistic regression model (LRM) and multi
      criteria analysis (MCA) methods to map the decadal permafrost distribution on the
      QTP and to assess permafrost dynamics from the 1980s to 2000s. The occurrence of
      permafrost and its impacting factors (i.e., climatic and topographic elements)
      were constructed from in-situ field investigation-derived permafrost distribution
      patterns in 4 selected study regions. The validation results indicate that both
      LRM and MCA could efficiently map the permafrost distribution on the QTP. The
      areas of permafrost simulated by LRM and MCA are 1.23 * 106 km2 and 1.20 * 106
      km2, respectively, between 2008 and 2012. The LRM and MCA modeling results
      revealed that permafrost area has significantly decreased at a rate of 0.066 *
      106 km2 decade-1 over the past 30 years, and the decrease of permafrost area is
      accelerating. The sensitivity test results indicated that LRM did well in
      identifying the spatial distribution of permafrost and seasonally frozen ground,
      and MCA did well in reflecting permafrost dynamics. More parameters such as
      vegetation, soil property, and soil moisture are suggested to be integrated into
      the models to enhance the performance of both models.

PMID- 30212696
TI  - Adsorption mechanisms of five bisphenol analogues on PVC microplastics.
AB  - Polyvinyl chloride (PVC) plastics are easily embrittled and decomposed to
      microplastics in an aquatic environment. The plasticizers such as bisphenol A
      (BPA), bisphenol S (BPS) and their analogues might be released and adsorbed by
      the PVC microplastics causing consequential pollution to the ecosystem. Herein, a
      systematic study was performed to determine the adsorption mechanisms of five
      bisphenol analogues (BPA, BPS, BPF, BPB and BPAF) on PVC microplastics. The
      maximum adsorption efficiency reached 0.19 +/- 0.02 mg.g-1 (BPA), 0.15 +/- 0.01
      mg.g-1 (BPS), 0.16 +/- 0.01 mg.g-1 (BPF), 0.22 +/- 0.01 mg.g-1 (BPB), and 0.24 +/
      0.02 mg.g-1 (BPAF) at PVC dosage of 1.5 g.L-1. The kinetics study shows that the
      adsorption processes can be divided into three stages including external mass
      transport, intraparticle diffusion and dynamic equilibrium. The isotherm modeling
      shows a better fit of the adsorption results to the Freundlich isotherm compared
      to the Langmuir model. The thermodynamic study indicates the adsorption of all
      bisphenols as exothermic processes. Furthermore, the adsorption mechanisms of
      bisphenols were explicated intensively, with respect to hydrophobic interactions,
      electrostatic forces, and noncovalent bonds. A positive effect of hydrophobic
      interactions was identified for bisphenols adsorption on PVC microplastics, but
      an obvious inhibition by electrostatic repulsions was revealed for BPF due to its
      ionization in the neutral solution. In addition, noncovalent bonds (hydrogen and
      halogen bonds) may promote the adsorption of bisphenols on PVC microplastics.
      Finally, the desorption and competitive adsorption of five bisphenol analogues on
      the microplastics were provided together with a perspective for future works.

PMID- 30212697
TI  - Signs of adaptation to trace metal contamination in a common urban bird.
AB  - Metals and metalloids at elevated concentrations can be toxic to both humans and
      wildlife. In particular, lead exposure can act as a stressor to wildlife and
      cause negative effects on fitness. Any ability to adapt to stress caused by the
      negative effects of trace metal exposure would be beneficial for species living
      in contaminated environments. However, mechanisms for responding adaptively to
      metal contamination are not fully understood in free-living organisms. The
      Australian populations of the house sparrow (Passer domesticus) provides an
      excellent opportunity to study potential adaptation to environmental lead
      contamination because they have a commensal relationship with humans and are
      distributed broadly across Australian settlements including many long-term mining
      and smelting communities. To examine the potential for an evolutionary response
      to long-term lead exposure, we collected genomic SNP data using the house sparrow
      200 K SNP array, from 11 localities across the Australian distribution including
      two mining sites (Broken Hill and Mount Isa, which are two genetically
      independent populations) that have well-established elevated levels of lead
      contamination as well as trace metals and metalloids. We contrast these known
      contaminated locations to other lesser-contaminated environments. Using an
      ecological association genome scan method to identify genomic differentiation
      associated with estimates of lead contamination we identified 60 outlier loci
      across three tests. A total of 39 genes were found to be physically linked
      (within 20 kbps) of all outliers in the house sparrow reference genome. The
      linked candidate genes included 12 genes relevant to lead exposure, such as two
      metal transporters that can transport metals including lead and zinc across cell
      membranes. These candidate genes provide targets for follow up experiments
      comparing resilience to lead exposure between populations exposed to varied
      levels of lead contamination.

PMID- 30212698
TI  - Phosphorus footprint in China over the 1961-2050 period: Historical perspective
      and future prospect.
AB  - The phosphorus footprint (PF) is a novel concept to analyze human burdens on
      phosphorus resources. However, research on PF approach is still limited, and
      current several PF studies include incomplete phosphorus sources and have limited
      quantitative interpretation about the drivers of PF changes, which can help
      understand future trends of PF. This study develops a more comprehensive PF model
      by considering crop, livestock and aquatic food, and non-food goods, which covers
      the mainly phosphorus containing products consumed by human. The model is applied
      to quantify China's PF from 1961 to 2014, and the results of the model are also
      used to analyze the factors driving the PF changes and explored China's PF
      scenarios for 2050 using an econometric analysis model (STIRPAT). The result
      shows that China's PF increased over 11-fold, from 0.9 to 10.6 Tg between 1961
      and 2014. The PF of livestock food dominated China's PF, accounting for 57% of
      the total in 1961 and 45% in 2014. The key factors driving the increase in
      China's PF are the increase in population and urbanization rate, with
      contributions of 38% and 33%, respectively. We showed that in the baseline
      scenario, China's PF would increase by 70% during 2014-2050 and cause the
      depletion of China's phosphate reserves in 2045. However, in the best case
      scenario, China's PF would decrease by 15% in 2050 compared with that in 2014,
      and it would have 50% of current phosphate reserve remaining by 2050. Several
      mitigation measures are then proposed by considering China's realities from both
      production and consumption perspective, which can provide valuable policy
      insights to other rapid developing countries to mitigate the P footprint.

PMID- 30212699
TI  - Corrigendum to "Application of response surface methodology in physicochemical
      removal of dyes from wastewater: A critical review" [Sci. Total Environ. 640
      641(2018) 772-797].

PMID- 30212700
TI  - Effects of elevated CO2 on plant C-N-P stoichiometry in terrestrial ecosystems: A
      meta-analysis.
AB  - A substantial number of experiments have so far been carried out to study the
      response of the C-N-P stoichiometry of terrestrial plants to the rising CO2 level
      of the earth. However, there is a need of systematic evaluation for assessing the
      impact of the elevated CO2 on plant C-N-P stoichiometry. In the present
      investigation, a comprehensive meta-analysis involving 386 published reports and
      including 4481 observations has been carried out. The goal of the research was to
      determine the response of plants to their C-N-P stoichiometry due to elevated
      levels of global atmospheric CO2. The results showed that rising CO2 altered the
      concentration of C (+2.19%, P < 0.05), N (-9.73%, P < 0.001) and P (-3.23%, P <
      0.001) and C:N (+13.29%, P < 0.001) and N:P ratios (-7.32%, P < 0.0001). Overall,
      a slightly increasing trend in the C:P ratio (P > 0.05) in the plant was
      observed. However, plant leaf, shoot and herbaceous type of plants showed more
      sensitivity to rising CO2. CO2 magnitude exhibited a positive effect (P < 0.05)
      on C:N ratio. Additionally, "CO2 acclimation" hypothesis as proposed by the
      authors of the current paper was also tested in the study. Results obtained,
      especially, show changes of C and N concentrations and C:P ratio to an obvious
      down-regulation for long-term CO2 fumigation. At spatial scales, a reduction of
      plant N concentration was found to be higher in the southern hemisphere. The CO2
      enrichment methods affected the plant C-N-P stoichiometry. Compared to FACE (free
      air CO2 enrichment), OTC (open top chamber) showed larger changes of C, N, P, and
      N:P. The results of the present study should, therefore, become helpful to offer
      a better understanding towards the response of the terrestrial plant C-N-P
      stoichiometry to an elevated global atmospheric CO2 in the future.

PMID- 30212701
TI  - Occurrence of organophosphorus flame retardants and plasticizers in wild insects
      from a former e-waste recycling site in the Guangdong province, South China.
AB  - Due to the fast growth of the electronic industry, a large quantity of electronic
      waste (e-waste) is generated worldwide and then often inappropriately dismantled
      and disposed of. In a pilot study, the occurrence of organophosphorus flame
      retardants and plasticizers (PFRs) was investigated for the first time in several
      wild insect species collected from a former e-waste recycling site in the
      Guangdong province, South China. TEHP was the most abundant PFR (average
      concentration of 5.8 ng/g ww), followed by TPHP (2.5 ng/g ww), TCIPP (2.2 ng/g
      ww), TCEP (0.8 ng/g ww), EHDPHP and TCP (both 0.1 ng/g ww). Dragonfly nymphs were
      the most contaminated insects, with total PFR concentrations of 68 ng/g ww,
      followed by moth adults (26 ng/g ww) and terrestrial stinkbug (17 ng/g ww). The
      different contamination patterns observed in the analyzed insects could be
      explained by their different habitats and feeding habits. This study shows that e
      waste recycling areas can be an important local source of contamination with
      PFRs, mainly caused by inadequate recycling activities.

PMID- 30212702
TI  - Assessing the impact of long-term changes in climate and atmospheric deposition
      on a shallow alpine lake from southeast Tibet.
AB  - Regional warming and atmospheric nitrogen deposition have been widely recorded to
      impact remote catchments and alpine lakes; however, their independent roles and
      interactions have rarely been identified. Here, we combined down-core analyses of
      sedimentary mercury (Hg) and aluminum (Al) with multiple proxies (i.e. nitrogen
      stable isotope, chlorophyll a pigments, diatoms) for a radiometrically-dated
      sediment core of an alpine lake in southeast Tibet to track the atmospheric
      deposition of pollutants, and to examine possible effects of climate and
      catchment forcing over the past three centuries. The sediment data revealed that
      airborne deposition of Hg was recorded from the ~1860s, with an accelerating
      increase in anthropogenic Hg flux since the ~1960s. A synchronous decrease in
      reconstructed lake-water TOC indicated that acid deposition may have affected
      lake-water carbon concentrations and impaired catchment export of decomposed
      organic matter (OM). A moderate depletion of bulk sediment delta15N started from
      the ~1820s, but was followed by an enriching trend after the ~1970s. This
      positive shift of delta15N was associated with elevated sediment OM and decreased
      catchment runoff of clastic materials (as inferred by Al). Sediment OM content
      displayed an accelerating increase from the ~1960s, with an increased input of
      autochthonous sources (i.e. lower bulk sediment C:N ratios), such as algae (as
      inferred by sedimentary chlorophyll a pigments). Meanwhile, climate warming and
      decreased lake-water TOC enhanced the production of algae, which was
      characterized by a more enriched delta15N signal than that of allochthonous OM.
      Furthermore, atmospheric acid deposition was significantly related to diatom
      assemblage changes, with an increase in acidophilous taxa. Our sediment evidence
      revealed the dominating impact of climate and catchment processes on lake-water
      chemistry and algal shifts in the context of atmospheric nitrogen deposition, and
      highlighted an increasing link of external forcing with in-lake processes in
      enriching sediment delta15N signal over the last few decades.

PMID- 30212703
TI  - Heavy metal contamination and health risk assessment for children near a large Cu
      smelter in central China.
AB  - Nonferrous metallurgy is causing significant concerns due to its emissions of
      heavy metals into environment, degrading environmental quality, and consequently
      posing high risks to human health. In this study, the concentration levels of
      Cadmium (Cd), Copper (Cu), Lead (Pb), and Arsenic (As) were investigated in soil,
      crop, well water, and fish samples collected around the Daye Copper Smelter in
      Hubei province, China, and the potential health risks were assessed for local
      children. The results showed that soils near the smelter were heavily polluted by
      Cd, Cu, Pb, and As, with the mean concentrations of 4.87, 195.26, 92.65, and
      35.84 mg/kg, respectively, which were significantly higher than the values of
      soil Cd (0.18 mg/kg), Cu (32.84 mg/kg), Pb (28.46 mg/kg), and As (13.65 mg/kg) in
      the reference area (p < 0.001). The concentrations of Cd and As in vegetable
      samples collected from smelter-affected area exceeded the maximum permissible
      level (MPL) for food in China by 82% and 39%, respectively. The concentrations of
      Cd and Pb in rice grain harvested from smelter-affected area were 9.35 and 1.35
      times higher than the corresponding MPL, respectively. The concentrations of Cd,
      As, and Cu in fish muscle from smelter-affected area exceeded the national MPL by
      72%, 41%, and 24% of analyzed samples, respectively. The concentrations of Cd (p
      < 0.05) and As (p < 0.01) in well water were significantly higher in the smelter
      affected area than those in the reference area, respectively. The health risks to
      local children in the smelter-affected area were 30.25 times higher than the
      acceptable level of 1, and most of the risks were resulted from Cd (46%), As
      (27%) and Pb (20%). The intake of crops was a major source (78%) to health risks
      for local children.

PMID- 30212704
TI  - Agricultural irrigation of vine crops from desalinated and brackish groundwater
      under an economic perspective. A case study in Siggiewi, Malta.
AB  - Maltese agriculture faces great challenges due to the severe scarcity of water.
      Sufficient water resources, in quantity and quality, are necessary to cover the
      demand in the production of wine grape, one of the most important crops in
      Maltese agriculture. But also, economic efficiency is essential in the grape
      cultivation. A Cost-Benefit Analysis (CBA) is defined for Maltese vineyards in
      the Siggiewi region, considering two irrigation scenarios, irrigation with
      groundwater or "do-nothing", compared with the "use non-conventional waters" from
      mixing water from a small desalination plant and groundwater. For the alternative
      'mixing desalinated water with groundwater' it is possible to improve water
      availability and quality for vine crops, while increasing economic benefits for
      farmer. The results indicate a profitable project from a minimum area of 1 ha,
      but final benefit is highly dependent on the irrigated surface extension
      according to water price. Desalination, compared with other type of non
      conventional water is considered the best option in this assessment with a small
      reverse osmosis (RO) desalination plant (120 m3/day) for covering the irrigation
      needs.

PMID- 30212705
TI  - Student midwives' intention to deliver weight management interventions: A theory
      of planned behaviour & self-determination theory approach.
AB  - OBJECTIVES: Overweight and obesity during pregnancy is a risk to the health of
      mother and child. Midwives can modify this key risk factor by providing weight
      management interventions to women before and during pregnancy. This study
      investigated social cognitive determinants of pre-clinical student midwives'
      intention to provide weight management intervention in preconception and
      antenatal clinical contexts. Social cognitive determinants from the theory of
      planned behaviour (attitudes, subjective norms, perceived behavioural control)
      and self-determination theory (autonomous motivation) were used to predict pre
      clinical students' intentions once they enter practice. METHOD: The sample was
      183 female pre-clinical student midwives from 17 Australian universities (age
      range = 18-54 years). Participants received a cross-sectional questionnaire that
      measured demographic items, attitudes, subjective norms, perceived behavioural
      control and autonomous motivation towards providing weight management
      intervention at two different stages of pregnancy - preconception and antenatal.
      RESULTS: Attitudes, subjective norms, and perceived behavioural control accounted
      for 56% of intention to provide weight management interventions to women planning
      pregnancy; however, the addition of autonomous motivation was non-significant. In
      contrast, attitudes and subjective norms (but not perceived behavioural control)
      accounted for 39% of intention to provide weight management interventions to
      women during pregnancy. Furthermore, the addition of autonomous motivation to the
      model was significant and accounted for an additional 3.1% of variance being
      explained. IMPLICATIONS AND CONCLUSIONS: Curriculum changes that support and
      increase pre-clinical student midwives' intention should focus on these specific
      correlates of intention in order to foster long term changes in clinical
      practice. Changes to the education and training of midwives should be carefully
      considered to understand their impact on these important determinants of
      intention to engage in this critical clinical skill.

PMID- 30212706
TI  - Student-faculty relationships and its impact on academic outcomes.
AB  - OBJECTIVE: The aim of this review of the literature is to synthesis the knowledge
      attained about determinants of student-faculty relationships and its impact on
      student outcomes. While adding to the body knowledge, the researchers discuss the
      importance, barriers, and facilitators to student-faculty academic relationships
      in nursing education. DESIGN: We conducted a narrative literature review using a
      modified version of the framework of the Population, Intervention, Comparison,
      and Outcome method to develop the research question for this review. That
      question was: What determinants of undergraduate nursing students' relationships
      with faculty affect those students' academic outcomes? DATA SOURCES: To search
      and review the literature systematically, we entered the specific criteria into
      the EBSCOhost interface. The following databases were used for data sourcing:
      Cumulative Index to Nursing and Allied Health Literature Plus with Full Text;
      Teacher Reference Center; Education Resources Information Center; Medline; and
      Theses and Dissertations. We selected only full-text, peer-reviewed sources that
      were written in English for final inclusion. REVIEW METHODS: After the retrieval
      of 56 reports via an EBSCO host search, abstracts were reviewed and 29 were
      rejected based on the exclusion/inclusion criteria. The rejected reports met some
      or no criteria and not others; or showed little to no association with
      determinants of nursing student-faculty academic relationships or students'
      academic outcomes. An inductive method of analysis was used to review and extract
      emerging themes. RESULTS: Findings revealed four core determinants of student
      faculty relationships: support, caring, diversity, and incivility. These
      determinants were interrelated and appeared to have an impact on student academic
      outcomes. CONCLUSIONS: Nursing institutions should be proactive to ensure that
      barriers such as incivility are reduced and that diversity is included and
      appreciated in the teaching and learning environment. Additionally, a caring and
      supportive climate of learning should be emphasized and enacted by nurse
      educators.

PMID- 30212707
TI  - RIPK4 promoted the tumorigenicity of nasopharyngeal carcinoma cells.
AB  - RIPK4 (receptor interacting serine/threonine kinase 4) has been reported to be
      aberrantly expressed in several cancer types. However, its expression pattern and
      functions in nasopharyngeal carcinoma (NPC) have never been reported. In this
      study, we have shown that the expression of RIPK4 was up-regulated in NPC
      tissues. RIPK4 promoted the growth and anchorage-independent growth of NPC cells,
      and down-regulation of RIPK4 inhibited the growth of NPC cells both in the plate
      based culture and on the soft agar. Moreover, RIPK4 promoted the expression of
      VEGF in the NPC cells and induced the tube formation of HUVEC, and Axitinib (the
      inhibitor for VEGF receptor) inhibited the tumorigenesis driven by RIPK4. In the
      molecular mechanism study, RIPK4 was found to enhance the interaction between
      IKKalpha and IKKbeta, and activated NF-kB signaling. Taken together, our study
      demonstrated the oncogenic roles of RIPK4 in NPC and suggested that RIPK4 might
      be a therapeutic target.

PMID- 30212708
TI  - Amelioration of oxidative stress in differentiated neuronal cells by rutin
      regulated by a concentration switch.
AB  - Increasing studies have implicated superfluous production of reactive oxygen
      species (ROS) as a significant factor in the progress of neurodegenerative
      disorders ranging from ischemic stroke to amyotrophic lateral sclerosis. The
      possible mechanisms relating to oxidative stress and neurodegeneration are yet to
      be thoroughly understood. Rutin, a flavonoid, has been well documented for its
      beneficial and pharmacological activities against diverse targets. However, the
      mechanism involved in the beneficial effects of rutin against neurodegeneration
      still remains unclear. Our study investigates the concentration switch effects of
      rutin on differentiated human neuroblastoma cells (IMR32) in vitro to unveil the
      possible mechanism of its action. IMR32 cells were differentiated using retinoic
      acid and challenged with different doses of rutin for 24 h duration to study the
      influence of ROS on differentiated neuronal cells and ROS-mediated apoptosis. The
      study showed that the high (100 MUM) and low (100 nM and 10MUM) rutin
      concentrations significantly avert ROS generation by two different mechanisms, by
      enhancing apoptosis through the modulation of levels of Bcl2, Caspase-3, survivin
      and its antioxidant activity via stress-related proteins, JNK and p38 MAPK. Our
      study suggests that rutin is a multi-targeted therapeutic and preventive agent
      that may act as an adjuvant complementary therapeutic molecule to treat oxidative
      stress-mediated neurodegeneration.

PMID- 30212709
TI  - miR-217 represses TGF-beta1-induced airway smooth muscle cell proliferation and
      migration through targeting ZEB1.
AB  - Aberrant proliferation and migration of airway smooth muscle cells (ASMCs)
      contribute to the pathogenesis of airway remodeling during asthma development.
      Here, the potential function of microRNA-217 (miR-217) on the cell proliferation
      and migration of TGF-beta1-induced ASMCs and the involved mechanisms were
      investigated in this study. We found that miR-217 expression was apparently
      downregulated in a time and dose dependent characteristic in ASMCs exposed to
      transforming growth factor-beta (TGF-beta1) stimulation. Overexpression of miR
      217 significantly inhibited TGF-beta1-induced proliferation, migration,
      extracellular matrix (ECM) deposition, but promoted apoptosis in ASMCs, whereas,
      miR-217 inhibitor showed an opposed effect. Bioinformatics analyses revealed that
      the 3'-untranslated region (UTR) of ZEB1 was a potential target for miR-217,
      which was further confirmed by luciferase activity, qRT-PCR and western blot
      assay. In addition, rescue experiment also displayed that restoration of ZEB1
      expression partially abrogated the inhibitory effect of miR-217 on TGF-beta1
      induced proliferation and migration in ASMCs. By chromatin immunoprecipitation
      (ChIP) assay, we further confirmed that the binding of ZEB1 to the fibronectin
      promoter in TGF-beta1-treated ASMCs was reduced by miR-217 overexpression.
      Therefore, our findings suggested the potential protective role of miR-217 on the
      attenuation of cell proliferation and migration was through targeting ZEB1 in TGF
      beta1-stimulated ASMCs.

PMID- 30212710
TI  - Down-regulation of microRNA-21 reduces inflammation and podocyte apoptosis in
      diabetic nephropathy by relieving the repression of TIMP3 expression.
AB  - BACKGROUND: Several miRNAs including miR-21 have emerged as important regulators
      in the development of diabetic nephropathy (DN). However, the molecular mechanism
      of miR-21 underlying DN pathogenesis remains to be further discussed. METHODS:
      Streptozotocin (STZ)-induced DN rats and high glucose (HG)-induced podocytes were
      used as the in vivo and in vitro models of DN. miR-21 level was detected by qRT
      PCR assay. Inflammatory cytokine levels were assessed by ELISA. Kidney injury of
      rats was evaluated by blood glucose, serum creatinine and blood urine nitrogen
      concentrations and periodic acid schiff (PAS) staining. Apoptosis in kidney
      tissues and podocytes was determined by TUNEL and flow cytometry analyses,
      respectively. Western blot analysis was applied to measure the protein levels of
      tissue inhibitors of metalloproteinase 3 (TIMP3), Bax and Bcl-2. The relationship
      between TIMP3 and miR-21 was confirmed by luciferase reporter assay. RESULTS: miR
      21 expression was upregulated in serum and kidney tissues of DN patients, kidney
      tissues of STZ-induced DN rats, and HG-treated podocytes. miR-21 depletion
      inhibited pro-inflammatory factor (IL-1beta, TNF-alpha) secretions and alleviated
      kidney damages in STZ-induced DN rats. Moreover, TIMP3 was a target of miR-21 in
      HG-treated podocytes. Additionally, TIMP3 overexpression abated HG-induced
      inflammatory responses and podocyte apoptosis. Furthermore, the inhibitory
      effects of TIMP3 on inflammatory responses and podocyte apoptosis were alleviated
      by increased miR-21. CONCLUSION: The down-regulation of miR-21 inhibited the
      progression of DN by targeting TIMP3 in STZ-induced DN rats and HG-treated
      podocytes, elucidating a novel regulatory mechanism of miR-21 in DN progression
      and offering a potential target for DN therapy.

PMID- 30212712
TI  - In situ oxidation and reduction of cerium dioxide nanoparticles studied by
      scanning transmission electron microscopy.
AB  - Cerium dioxide nanocubes and truncated octahedra were reduced and oxidized in the
      scanning transmission electron microscope. The reduction process was stimulated
      by the electron beam and oxidation was supported by background gases in the
      microscope environment. High-angle annular dark field imaging is sensitive to
      local lattice distortions that arise as oxygen vacancies are created and cerium
      cations reduce enabling high spatial resolution characterization of this process
      with temporal resolution on the order of seconds. Such measurements enable us to
      differentiate and infer that the observed behavior between the nanocubes and
      truncated octahedra may be due to the difference in crystallographic termination
      of surfaces. In situ measurements taken with different partial pressures of
      oxygen reveal the cerium oxidation state and the dose rate threshold for the
      onset of beam reduction are influenced by the environment. Increasing oxygen
      partial pressure reduces the Ce3+ content and decreases susceptibility to
      electron beam driven reduction.

PMID- 30212711
TI  - Dopamine-dependent cognitive processes after menopause: the relationship between
      COMT genotype, estradiol, and working memory.
AB  - The present study examined how a gene related to functioning of the dopaminergic
      system, catechol-O-methyltransferase (COMT), and estradiol were related to brain
      functioning in healthy postmenopausal women. Participants were 118 healthy,
      cognitively normal postmenopausal women between the ages of 50-60 years. All
      women provided a blood sample for COMT and estradiol analyses and underwent a
      magnetic resonance imaging scan. Working memory performance and related brain
      activation were measured with BOLD functional magnetic resonance imaging during
      the N-back task. Results were examined across each COMT genotype and a median
      split was performed on the circulating estradiol levels to create high and low
      estradiol groups for each genotype. COMT genotype and estradiol level were
      hypothesized to be proxy measures for brain dopamine levels with the Met/Met and
      high estradiol group having the most dopamine and Val/Val and low estradiol group
      having the least dopamine. The functional magnetic resonance imaging results
      showed that the N-back task activated the expected bilateral frontal and
      bilateral parietal working memory network. However, no main effects of COMT
      genotype or estradiol group were found. There was COMT-estradiol interaction
      found in a small area of decreased activation in the right precentral gyrus
      (Brodmann Area 6) that was related to the increasing hypothesized dopamine level.
      Specifically, women with a Met/Met genotype in the high estradiol group had the
      least activation in this frontal lobe working memory region. Women with a Val/Val
      genotype in the low estradiol group had greater activation in this region
      relative to the other groups. Performance on the N-back task did not show any
      group differences. These data indicate that after menopause COMT genotype and
      potentially the menopause-related changes to the dopaminergic system are not
      related to cognition. Future studies should examine how the relationship between
      COMT, estradiol, and cognition around the menopause transition as there appear to
      be differences in this relationship for premenopausal and postmenopausal women.

PMID- 30212713
TI  - Neuromodulation of hippocampal long-term synaptic plasticity.
AB  - Multiple neuromodulators including acetylcholine, noradrenaline, dopamine and
      serotonin are released in response to uncertainty to focus attention on events
      where the predicted outcome does not match observed reality. In these situations,
      internal representations need to be updated, a process that requires long-term
      synaptic plasticity. Through a variety of common and divergent mechanisms, it is
      recently shown that all these neuromodulators facilitate the induction and/or
      expression of long-term synaptic plasticity within the hippocampus. Under
      physiological conditions, this may be critical for suprathreshold induction of
      plasticity endowing neuromodulators with a gating function and providing a
      mechanism by which neuromodulators enable the targeted updating of memory with
      relevant information to improve the accuracy of future predictions.

PMID- 30212714
TI  - Homeostatic synaptic plasticity as a metaplasticity mechanism - a molecular and
      cellular perspective.
AB  - The molecular mechanisms underlying various types of synaptic plasticity are
      historically regarded as separate processes involved in independent cellular
      events. However, recent progress in our molecular understanding of Hebbian and
      homeostatic synaptic plasticity supports the observation that these two types of
      plasticity share common cellular events, and are often altered together in
      neurological diseases. Here, we discuss the emerging concept of homeostatic
      synaptic plasticity as a metaplasticity mechanism with a focus on cellular
      signaling processes that enable a direct interaction between Hebbian and
      homeostatic plasticity. We also identify distinct and shared molecular players
      involved in these cellular processes that may be explored experimentally in
      future studies to test the hypothesis that homeostatic synaptic plasticity serves
      as a metaplasticity mechanism to integrate changes in neuronal activity and
      support optimal Hebbian learning.

PMID- 30212715
TI  - Discourse-based treatment in mild traumatic brain injury.
AB  - BACKGROUND: Individuals with traumatic brain injury (TBI) present with numerous
      discourse deficits associated with impairments to the linguistic system and other
      cognitive systems. Individuals with TBI may produce discourse that is lacking
      important information and poorly organized, as well as containing numerous
      coherence disrupting elements. Yet there are few studies directly addressing
      discourse deficits in individuals with TBI to guide clinicians. AIMS: The purpose
      of the study was to determine if discourse processing treatment improved the
      discourse production in individual with TBI. Aims of the study included
      determining if the discourse processing treatment improved completeness and
      informativeness in TBI discourse samples. METHODS & PROCEDURES: The study
      included three participants with mild-to-moderate TBI. The study utilized an A-B
      with maintenance design that incorporated components of functional practice,
      structured cues in the form of comprehension questions and story guide, and meta
      cognitive and meta-linguistic processes. Discourse samples were obtained for
      baseline, treatment, and maintenance one-week and one-month post treatment.
      Stimuli included 12 sequential pictures, as well as a single picture and a
      recount probe. OUTCOMES & RESULTS: All participants demonstrated small gains in
      completeness and informativeness for treated items, and 2 of 3 participants
      demonstrated a medium therapeutic effect for untreated stimuli. Participants also
      produced discourse with fewer errors for both treated and untreated stimuli after
      treatment with no therapeutic effect to a small effect for the generalization
      stimuli. CONCLUSIONS: The study demonstrated that the discourse processing
      treatment is capable of producing small therapeutic effects that persisted one
      month post treatment in adults with mild-to-moderate TBI.

PMID- 30212717
TI  - Disinfection by-products formation and ecotoxicological effects of effluents
      treated with peracetic acid: A review.
AB  - Peracetic acid (PAA) has gained increasing attention over the last decades as a
      suitable and environmentally-friendly alternative to chlorine-based compounds for
      wastewater disinfection, claiming limited disinfection by-products (DBPs) formed
      and no persistent residues in the environment. The present work aims at
      presenting a comprehensive and updated review of the ecotoxicological effects of
      effluents treated with PAA, to be ascribed to residual PAA and hydrogen peroxide
      (H2O2) and DBP formation. Modest concentrations of DBPs have been observed after
      PAA treatment, mainly carboxylic acids, which are not recognized as genotoxic.
      Moreover, there is no evidence of any endocrine disruption potential of PAA in
      human health or in the ecotoxicological studies. The associated H2O2 fraction can
      potentially minimize the formation of halogenated DBPs and also contribute to the
      acute toxic effects of treated effluents. Effluents disinfected with PAA at
      concentrations typical of the wastewater treatment field have displayed limited
      toxic, mutagenic and genotoxic effects on different aquatic organisms,
      particularly low compared to chlorine-based disinfectants.

PMID- 30212716
TI  - Cosmetic camouflage improves quality of life among patients with skin
      disfigurement: A systematic review.
AB  - This study systematically reviewed the impact of cosmetic camouflage use on
      different psychosocial outcomes in patients with disfiguring skin disorders.
      Electronic databases and reference lists were searched in February 2018 for
      studies reporting the impact of cosmetic camouflage on different quality of life
      (QoL) outcomes. Eighteen studies met the inclusion criteria: six randomized
      controlled trials, two quasi-experimental studies, nine single group 'before and
      after' interventions, and one comparative study with single post-intervention
      measurement. Quality appraisal of included studies was undertaken using the
      Joanna Briggs critical appraisal tools. While the studies varied in design, those
      included in this review indicated significant improvement in QoL after the use of
      cosmetic camouflage. The mean reduction in Dermatological Life Quality Index
      scores ranged from 1.4 to 6.4 signifying improvement in QoL of participants after
      treatment with cosmetic camouflage. Cosmetic camouflage can be an effective
      therapy in improving QoL among patients with skin disfigurement.

PMID- 30212718
TI  - Gold-based nanospheres and nanorods particles used as theranostic agents: An in
      vitro and in vivo toxicology studies.
AB  - The adverse effect of gold-based nanoparticles is still an open question since it
      depends on several factors as shape, surface charge or route of administration.
      In this study, we investigated the influence of shape and human serum albumin
      (HSA) coating on the adverse effects of spherical (AuNP) and nanorods (AuNR) gold
      based particles. F C3H (fibroblast) and HTC (hepatocellular carcinoma) cell lines
      both from liver were exposed to 25, 75 and 125 MUg mL-1, which correspond to 109
      NP mL-1. For in vivo studies, Wistar rats received these materials by oral
      administration in doses of 10 MUg kg-1 or 40 MUg kg-1. Systemic toxicity was
      verified after 24 h and 48 h by morphological analysis, blood parameters and
      myeloperoxidase enzyme activity. Our results revealed that HSA corona does not
      influence totally the pathway of interactions between AuNP and AuNR. In vitro
      results evidenced that AuNP can decrease in at least 50% viability of F C3H and
      cell adhesion of HTC, but corona significantly overcomes these effects. No
      differences between shape or corona were observed in function of cell lines. In
      vivo studies showed that 40 MUg kg-1 of AuNP-HSA caused an enhancement of the
      myeloperoxidase response indicating inflammatory processes. An increase from 40%
      to 80% on alkaline phosphatase levels were found for all groups. Our findings
      suggested that gold-based particles coated or not with HSA do not cause
      expressive adverse effects on in vitro or in vivo systems, and their oral
      administration cannot cause a systemic effect in the experimental conditions used
      here.

PMID- 30212719
TI  - Identification of the influence of distal inputs on mercury loading across the
      mid Great Lakes region using chemical sediment chronologies.
AB  - Sediment cores from 47 inland lakes in Michigan, USA were used to assess spatial
      and temporal trends in loadings of mercury (Hg). Focusing/background corrected
      accumulation rates and inventories and peak concentrations were used to examine:
      1) responses of loadings to post-1990 reductions in emissions, 2) if spatial
      trends are consistent with modeled Hg deposition and 3) evidence for local and
      distal inputs. Results showed that decreases in concentrations and anthropogenic
      accumulation rates of Hg were consistent with recent reductions in emissions of
      Hg. Most lakes exhibiting a decreasing trend were located within an area with the
      most emission sources. Not all lakes showed the decreasing trend with some
      showing increases or no change. These lakes tended to be in the northern portion
      of the state. In all lakes, current concentrations of Hg remain greater than long
      term, historical, background concentrations. Sub-regional mean inventories and
      mean decadal accumulation rates exhibited a south to north gradient, consistent
      with previously modeled spatial trends. However, individual lake inventories and
      rates of accumulation compared at shorter times scales varied among lakes.
      Evidence for event deposition (e.g., volcanic eruptions, manufacturing) was also
      variable among lakes. These results suggest influence of more distal inputs of
      Hg, perhaps driven by well-mixed, global sources. Cause(s) of variability on
      shorter time scales (e.g., events) needs further work. Finally, the results
      reveal that understanding risks to humans and ecosystems due to exposure to Hg
      and developing effective abatement policy is challenging.

PMID- 30212720
TI  - Zinc oxide nanoparticles induce toxicity by affecting cell wall integrity
      pathway, mitochondrial function and lipid homeostasis in Saccharomyces
      cerevisiae.
AB  - Growing numbers of nanotoxicity research demonstrating that mechanical damage and
      oxidative stress are potential modes of nanoparticles (NPs) induced toxicity.
      However, the underlying mechanisms by which NPs interact with the eukaryotic cell
      and affect their physiological and metabolic functions are not fully known. We
      investigated the toxic effects of zinc oxide nanoparticles (ZnO-NPs) on budding
      yeast, Saccharomyces cerevisiae and elucidated the underlying mechanism. We
      observed cell wall damage and accumulation of reactive oxygen species (ROS)
      leading to cell death upon ZnO-NPs exposure. We detected a significant change in
      the cellular distribution of lipid biosynthetic enzymes (Fas1 and Fas2).
      Furthermore, exposure of ZnO-NPs altered the architecture of endoplasmic
      reticulum (ER) and mitochondria as well as ER-mitochondria encounter structure
      (ERMES) complex causing cellular toxicity due to lipid disequilibrium and
      proteostasis. We also observed significant changes in heat shock and unfolded
      protein responses, monitored by Hsp104-GFP localization and cytosolic Hac1
      splicing respectively. Moreover, we observed activation of MAP kinases of CWI
      (Mpk1) and HOG (Hog1) pathways upon exposure to ZnO-NPs. Transcript level
      analyses showed induction of chitin synthesis and redox homeostasis genes.
      Finally, we observed induction in lipid droplets (LDs) formation, distorted
      vacuolar morphology and induction of autophagy as monitored by localization of
      Atg8p. However, we did not observe any significant change in epigenetic marks,
      examined by western blotting. Altogether, we provide evidence that exposure of
      ZnO-NPs results in cell death by affecting cell wall integrity and ER homeostasis
      as well as accumulation of ROS and saturated free fatty acids.

PMID- 30212721
TI  - Prediction of biopersistence of hydrocarbons using a single parameter.
AB  - Aerobic biodegradation is an important attenuation process for petroleum
      hydrocarbons (PHCs) in the natural environment. It has also been frequently used
      in engineered systems to remediate PHC-contaminated sites. A model such as a
      quantitative structure property relationship (QSPR) that can predict the
      biodegradation rate of PHCs would be helpful prior to implementing any extensive
      environmental measurements and bioremediation strategies. Existing QSPRs either
      have a large number of predictor variables that may cause overfitting or are
      based on a small dataset of PHCs. The goal of this study is to develop a simple,
      portable QSPR that has only a few predicator variables but can accurately predict
      the biodegradation half-lives of a large group of PHCs. To this end, more than
      500 molecular variables were screened, and candidate variables were refined by a
      feature selection method and fitted to biodegradation data of a group of
      structurally heterogeneous PHCs (n = 173). The model was established by means of
      hierarchical clustering and classification and regression tree algorithms, which
      was optimized by an internal validation procedure and validated by an external
      dataset. The optimal QSPR model, containing only one predictor variable (the
      number of bonds that do not contain hydrogen), was able to accurately predict
      biodegradation half-lives for a wide variety of PHCs. The internal validation
      test indicated an overall prediction accuracy of 93%, and predictions applied to
      an independent external set of 64 PHCs yielded 95% accuracy. The new model is
      transparent and easily portable from one user to another.

PMID- 30212722
TI  - Social determinants of emotional well-being in new refugees in the UK.
AB  - OBJECTIVES: Refugees are most vulnerable to mental health problems of all migrant
      groups, and an understanding of the role of postdisplacement social factors in
      refugee emotional well-being can help to shape the future interventions for this
      group. We aimed to investigate the effect of social determinants, such as
      employment, language ability and accommodation, on mental health in refugees in
      the UK. STUDY DESIGN: This prospective longitudinal cohort study was set in the
      UK. The study population of new UK refugees was drawn from an existing data set
      of the Longitudinal Survey of New Refugees (n = 5678), in which all new UK
      refugees (2005-2007) were sent a postal questionnaire at four time points across
      2 years. METHODS: Ordered logistic regression models were used to evaluate
      associations between social determinants and the dependent variables, emotional
      well-being or change in emotional well-being, using a question from the Short
      Form-36 Health Survey Questionnaire. RESULTS: Refugees who were unemployed in the
      UK, could not speak English well or were unsatisfied with their accommodation had
      significantly higher odds of poorer emotional well-being in the cross-sectional
      analysis (P < 0.05 at all time points measured). CONCLUSIONS: Postdisplacement
      social factors, including language ability, employment status and accommodation
      satisfaction, were important determinants of refugee emotional well-being.
      Changes in these social determinants have the potential to improve refugee mental
      health, making them legitimate, modifiable targets for important public health
      interventions. Accounting for this, further research into how to improve refugee
      well-being is crucial given the increase in refugee numbers around the developed
      world.

PMID- 30212723
TI  - Neuropsychology of frontal lobe epilepsy in children and adults: Systematic
      review and meta-analysis.
AB  - Frontal lobe epilepsy (FLE) is associated with cognitive problems, especially in
      areas related to frontal lobe functioning as executive functions, attention, and
      motor skills, but with impact on memory and psychosocial adaptation. Deficits are
      similar in both adults and children with FLE, although no studies have compared
      adult and pediatric performance in the same study. The aim of this research was
      to analyze the existing evidence concerning the cognition in adults and children
      with FLE. A random effect meta-analysis was used using Cohen's d, and the
      confidence interval for each cognitive factor was calculated. The results in the
      meta-analysis show a general pattern of cognitive dysfunction in FLE, especially
      in functions related to the frontal lobe, with an influence of the duration and
      the age at onset of epilepsy, as well as the age of the sample used. In addition,
      researches in this type of epilepsy are heterogeneous, with too many different
      sampling and methodological characteristics, which is not a standard format for
      reporting clinical sample characterization, making it difficult to study FLE in
      depth.

PMID- 30212724
TI  - Epileptic auditory illusions as reliable findings in the determination of the
      lateralization and localization of epileptogenic zone.

PMID- 30212725
TI  - Cognitive features and surgical outcome of patients with long-term epilepsy
      associated tumors (LEATs) within the temporal lobe.
AB  - OBJECTIVE: The objective of the study was to evaluate cognitive and epilepsy
      related features in 166 surgically treated patients with epilepsy with long-term
      epilepsy-associated tumors (LEATs) located in the temporal lobe. METHOD: Pre- and
      postsurgical cognitive as well as the one-year seizure outcome of adult patients
      with histopathologically confirmed LEATs (28 grade-I dysembryoplastic
      neuroepithelial tumors (DNET), 95 grade-I gangliogliomas (GG), 24 grade-I
      pilocytic astrocytomas (PA), 9 grade-II pleomorphic xanthoastrocytoma (PXA), 10
      grade-II diffuse astrocytoma (DA)) who underwent epilepsy surgery in Bonn/Germany
      between 1988 and 2012 were evaluated. RESULTS: At baseline, tumor groups differed
      in regard to age at epilepsy onset and location within the temporal lobe.
      Postoperative seizure freedom was achieved most frequently (>77.8%) in DNET, GG,
      and DA, less often in PXA (62.5%) and the least in PA (56.5%). Preoperative
      memory was impaired in 67.1% of all patients, executive functions in 44.7%, and
      language in 45.5%. Patients with PA displayed the poorest cognitive performance.
      Individual significant memory decline that was observed in 27.1% of all patients
      was predicted by left-sided surgery, a mesial pathology, and extended hippocampal
      resection. Executive functions depended on antiepileptic drug (AED) load and
      remained stable (72.0%) or even improved (21.6%) after surgery. Language
      functions were unchanged in 89.5% of patients. CONCLUSION: Patients with LEATs in
      the temporal lobe frequently show cognitive impairments. Predictors for pre- and
      postoperative cognition mostly correspond to what is known for temporal lobe
      epilepsy and resections in general. However, different tumor types appear to be
      associated with different cognitive and seizure outcomes with astrocytoma as the
      least benefitted group.

PMID- 30212726
TI  - Integrating the systematic assessment of psychological states in the epilepsy
      monitoring unit: Concept and compliance.
AB  - BACKGROUND: Admission to the epilepsy monitoring unit (EMU) for long-term video
      electroencephalography (EEG) monitoring (VEEG) constitutes the gold standard for
      seizure diagnosis and presurgical evaluation. This study applied the concept of a
      high-frequency systematic monitoring of psychological states and tested patients'
      compliance in order to evaluate if its integration in the EMU is feasible and if
      patients benefit from the graphically underpinned discussion of their EMU stay
      related cognitions and emotions. METHODS: The process-monitoring is technically
      realized by an internet-based device for data collection and data analysis, the
      Synergetic Navigation System (SNS). A convenient sample was enrolled: All
      eligible patients who were admitted to the EMU of the Department of Neurology,
      Christian Doppler Medical Center, Salzburg, Austria, between November 6th 2017
      and January 26th 2018 were approached and recruited upon consent. After a short
      resource-oriented interview, each enrolled patient was provided with a tablet.
      The daily questionnaire included eight standardized and up to three personalized
      items. Self-assessments were collected every 5 h prior to meal times (6:30 am,
      11:30 am, and 4:30 pm) and at 9:30 pm. The detailed visualizations of the
      patients' replies were discussed with the participants during a feedback session
      at the end of the EMU stay. RESULTS: Twenty-one patients (12 women/9 men, median
      age 29 years [range 18-74 years]) were consecutively recruited (72% of all
      eligible patients). Compliance rates were high (median: 82%, range 60%-100%)
      among the respondents. Mood correlated strongly with hopefulness (r = 0.71) and
      moderately with energy (r = 0.63) in all patients. When correlating the
      intraindividual medians of the process questionnaire time series with the pretest
      total scores, energy correlated moderately and negatively with the Perceived
      Stress Scale (PSS) (r = -0.45), while self-efficacy correlated moderately and
      negatively with the Neurological Disorders Depression Inventory for Epilepsy
      (NDDI-E) total scores in all patients (r = -0.5). Nine patients (43%) reported
      that they learned something meaningful about themselves after the feedback
      discussion of their individual time series. CONCLUSION: The results support the
      feasibility of high-frequency monitoring of psychological states and processes in
      routine EMU settings. Repeated daily collections four times per day of
      psychological surveys allow for the assessment of highly resolved, equidistant
      time series data, which gives insight into psychological states and processes
      during EMU admission.

PMID- 30212728
TI  - Maternal C-reactive protein and cytokine levels during pregnancy and the risk of
      selected neuropsychiatric disorders in offspring: A systematic review and meta
      analysis.
AB  - The pathophysiology of neuropsychiatric disorders is unclear. Increasing evidence
      has suggested maternal immune system dysregulation may be implicated in
      offspring's early brain development and related to an increased risk of
      neuropsychiatric disorders in offspring. The primary objective of this meta
      analysis was to investigate the association of maternal CRP and cytokine levels
      with offspring's neuropsychiatric disorders. We identified relevant studies
      following a search of PubMed, Web of Science, EMbase database between January
      1971 and February 2018. A meta-analysis was performed on studies which reported
      the association of prenatal maternal peripheral blood concentrations of CRP and
      cytokines with offspring's neuropsychiatric disorders. Results were reported
      according to PRISMA statement. Fifteen studies (six for maternal CRP, nine for
      maternal cytokines) were included in the meta-analysis, of which 80% were of high
      methodological quality. Random-effect meta-analysis showed that increasing
      maternal CRP (OR = 1.31, 95% CI 1.11-1.55, SMD = 0.15, 95% CI 0.06-0.24, P <
      0.01), pro-inflammatory cytokine interleukin (IL)-8 (OR = 1.64, 95% CI 1.06-2.55,
      SMD = 0.27, 95% CI 0.03-0.52, P = 0.03) and anti-inflammatory cytokine IL-10 (OR
      = 2.16, 95% CI 1.30-3.59, SMD = 0.43, 95% CI 0.14-0.71, P < 0.01) were
      significantly associated with schizophrenia in offspring. The finding of our meta
      analysis has identified significantly altered maternal CRP and cytokine
      concentrations in schizophrenia, strengthening evidence of maternal immune system
      dysregulation in neuropsychiatric disorders where inflammatory signals dominate.

PMID- 30212727
TI  - Differential relations of suicidality in depression to brain activation during
      emotional and executive processing.
AB  - Suicidal behavior is highly prevalent in major depressive disorder (MDD), though
      not present in all patients. It is unclear whether the tendency for suicidal
      behavior is associated with a unique functional neuroanatomical signature
      identifiable through neuroimaging. In this study, we investigated brain
      activation in suicidal and non-suicidal patients with MDD during facial emotion
      processing and executive control. Functional magnetic resonance imaging (fMRI)
      data from the NESDA-fMRI study (MDD patients N = 103, healthy controls N = 26,
      HC) were analyzed. Patients were divided in a group of suicide attempters (N =
      18, SA), suicide ideators (N = 31, SI) and a patient-control group (N = 73, PC).
      A gender discrimination task with emotional faces and the Tower of London
      executive planning task were investigated. An ANOVA was performed to compare
      brain activation among suicidal patients (SA + SI), PC and HC first and then
      among SI, SA, PC and HC. Significance was determined as meeting p < .05 family
      wise error (FWE) corrected at the voxel-level. We observed that SA patients
      showed lower activation in the bilateral fusiform gyri during emotional faces
      processing compared to SI, PC and HC. No group differences were found during
      executive planning. Results were independent of childhood emotional maltreatment,
      depression severity, anxiety severity, use of psychotherapy and SSRI-use. Results
      suggest that a propensity for suicidal behavior in MDD is associated with
      abnormal emotional processing but not executive functioning, represented by
      altered face processing compared to non-suicidal patients and controls. While in
      need of replication, these results indicate that altered fusiform gyrus
      activation during emotion processing may serve as a marker for suicidality.

PMID- 30212729
TI  - Low duty-cycle pulsed irradiation reduces magnetization transfer and increases
      the inhomogeneous magnetization transfer effect.
AB  - Intense off-resonant RF irradiation can lead to saturation of the macromolecular
      pool magnetization and enhance bound pool dipolar order responsible for the
      inhomogeneous magnetization transfer (ihMT) effect, but the intensity of RF power
      in human imaging studies is limited by safety constraints on RF heating. High RF
      intensities can still be achieved if applied in short pulses with low duty-cycle.
      Here we investigate the benefits of low duty-cycle irradiation for MT and ihMT
      studies with both theoretical and experimental methods. Solutions for pulsed
      irradiation of a two-pool model including dipolar order effects were implemented.
      Experiments were conducted at 3 T in the brain and through the calf of healthy
      human subjects. 2D echo planar images were acquired following a preparation of RF
      irradiation with a 2 s train of 5 ms pulses repeated from between 10 to 100 ms
      for duty-cycles (DCs) of 50% to 5%, and at varying offset frequencies, and time
      averaged RF powers. MT and ihMT data were measured in regions of interest within
      gray matter, white matter and muscle, and fit to the model. RF irradiation
      effects on signal intensity were reduced at 5% relative to 50% DCs. This reduced
      RF effect was much larger for single than dual frequency irradiation. 5% DC
      irradiation reduced single and dual frequency MT ratios but increased ihMT ratios
      up to 3 fold in brain tissues. Muscle ihMT increased by an even larger factor,
      depending on the frequency and applied power. The model predicted these changes
      with duty-cycle. The model fit the data well and constrained model parameters.
      Low duty-cycle pulsed irradiation reduces MT effects and markedly increases
      dipolar order effects. This approach is an attractive method to enhance ihMT
      signal-to-noise ratio and demonstrates a measurable ihMT effect in muscle tissue
      at 3 T under acceptable specific absorption rates. The effects of duty-cycle
      changes demonstrated in a separate MT/ihMT preparation provide a route for new
      applications in magnetization-prepared MRI sequences.

PMID- 30212730
TI  - Human skin volatiles: Passive sampling and GC * GC-ToFMS analysis as a tool to
      investigate the skin microbiome and interactions with anthropophilic mosquito
      disease vectors.
AB  - Volatile organic compounds (VOCs) emanating from the surfaces of human skin are
      of great interest to researchers in medical and forensic fields, as well as to
      biologists studying the ecology of blood-feeding insect vectors of human disease.
      Research involving the comparison of relative abundances of VOCs emanating from
      human skin is currently limited by the methodology used for sample collection and
      pre-concentration. The use of in-house developed silicone rubber
      (polydimethylsiloxane (PDMS)) passive sampling devices constructed in the form of
      bracelets and anklets was explored to address this need. The easy-to-use samplers
      were employed as non-invasive passive sampling devices for the non-targeted
      collection and concentration of volatile human skin emissions prior to thermal
      desorption thereof coupled with comprehensive gas chromatographic time-of-flight
      mass spectrometric (GC * GC-TOFMS) analysis. Compounds collected were from a wide
      range of compound classes. Several compounds, notably cyclic ketones, identified
      have not been previously reported in skin volatile literature. Comparison of
      normalized unique mass peak area signals has revealed relative quantitative
      differences and similarities between the samples collected from two individuals'
      wrists and as well as between an individual's wrist and ankle. The sampling
      method was evaluated based on its ability to provide many candidate compounds for
      potential biomarker discovery. The results show the ability of the new sampling
      method for augmenting the current knowledge on human skin volatile emissions. The
      samplers are both easy to use and economical. Applications explored include the
      study of the complex relationships between the human skin microbiome and the
      attractiveness of individuals to anthropophilic blood host seeking mosquitoes.

PMID- 30212731
TI  - HCPro-mediated transmission by aphids of purified virions does not require its
      silencing suppression function and correlates with its ability to coat cell
      microtubules in loss-of-function mutant studies.
AB  - Native and amino acid (aa) substitution mutants of HCPro from potato virus Y
      (PVY) were transiently expressed in Nicotiana benthamiana leaves. Properties of
      those HCPro variants with regard to silencing suppression activities, mediation
      of viral transmission by aphids, and subcellular localization dynamics, were
      determined. One mutant failed to suppress silencing in agropatch assays, but
      could efficiently mediate the transmission by aphids of purified virions. This
      mutant also retained the ability to translocate to microtubules (MTs) in stressed
      cells. By contrast, another single aa substitution mutant displayed native-like
      silencing suppression activity in agropatch assays, but could not mediate
      transmission of PVY virions by aphids, and could not relocate to MTs. Our data
      show that silencing suppression by HCPro is not required in the aphid-mediated
      transmission of purified virions. In addition, since the same single aa
      alteration compromised both, viral transmission and coating of MTs, those two
      properties could be functionally related.

PMID- 30212732
TI  - Inherent bacterial community response to multiple heavy metals in sediment from
      river-lake systems in the Poyang Lake, China.
AB  - Sediment is the one of most important storage of heavy metal. Microbiotas in
      sediment can be used as the effective indicators of heavy metals. The goal of
      this study was to understand the bacterial communities responding to heavy metal
      enrichment in sediments and prioritize some factors that affected significantly
      to bacterial community. Sediments were sampled from five river-lake systems in
      the Poyang Lake in dry season, and the bacterial community was analyzed using
      Illumina high-throughput sequencing. Relationships between sediment environment
      and the diversity and structure of bacterial communities were determined by
      correlation analysis and redundancy analysis (RDA). The result indicated that Cd
      and Sb were identified as the heavy metals of the great risk in sediments.
      Sediments from five river-lake systems shared 31.83% core operational taxonomic
      units (OTUs) of bacterial communities. Proteobacteria (33.54% of total sequences)
      and Actinobacteria (15.04%) were the dominant phyla across all sites. High
      enrichment of heavy metals (MRI and mCd) resulted in low diversity of bacterial
      communities (Simpson index). The RDA revealed pH, OC, mCd, and Efs of As, Pb, Cd
      were major factors related to bacterial community structure changes. The dominant
      phylum Actinobacteria was regarded as tolerant bacteria, while the dominant
      phylum Proteobacteria was named as resistant bacteria in sediment with high
      anthropogenic Cd enrichment.

PMID- 30212733
TI  - Macrophytes are highly sensitive to the herbicide diquat dibromide in test
      systems of varying complexity.
AB  - The herbicide diquat dibromide is used in North America to manage nuisance
      macrophytes. However, its effect on native macrophytes is less clear and it could
      cause indirect effects on other aquatic biota. This study determined the
      sensitivity of both native and non-native macrophytes grown in test systems with
      varying complexity to diquat dibromide applied directly to water following label
      directions. In an outdoor mesocosm experiment and single species greenhouse
      concentration-response tests, Elodea canadensis Michx., Myriophyllum spicatum L.,
      Ceratophyllum demersum L. and Hydrocharis morsus-ranae L. were exposed to a range
      of diquat dibromide concentrations (4.7 - 1153 ug/L), corresponding to 0.4 - 100%
      of the recommended label rate of the formulated product. The mesocosm experiment
      contained all four plant taxa in the same system along with caged amphipods
      (Hyalella azteca Saus.), tadpoles (Lithobates pipiens Schreber), phytoplankton
      and periphyton; however, this study focuses on the macrophytes only. In both test
      systems, severe direct effects of diquat dibromide on macrophytes were detected,
      with almost 100% mortality of all macrophytes in both test systems at 74 ug/L.
      The most sensitive species in the single species tests, E. canadensis, showed
      almost 100% mortality at concentrations below the HPLC-based method detection
      limit of 5 ug/L. Effects occurred very rapidly and showed no difference in
      severity between native and non-native macrophytes or complexity of test systems.
      These results suggest that diquat dibromide could be applied at a considerably
      lower label rate, depending on the characteristics of the waterbody, while still
      achieving effective control of nuisance macrophytes.

PMID- 30212734
TI  - Pb speciation in rare earth minerals and use of entropy and fuzzy clustering
      methods to assess the migration capacity of Pb during mining activities.
AB  - Ionic rare earth mining is of strategic importance in China; however, the heavy
      metal pollution it causes is of great concern, both at home and abroad. Data on
      Pb speciation at a rare earth mine were used to analyse the migration capacity of
      Pb during the process of ore leaching. The major factors thought to influence the
      migration capacity of Pb, including the clay mineral content, soil pH, oxidation
      reduction potential, organic matter content, and cation exchange capacity (CEC),
      were quantified. Entropy and fuzzy clustering methods were used to identify the
      most predictive factors. The results showed that the clay mineral content of the
      soil exerts the strongest influence on the migration capacity of Pb in rare earth
      mines; the other factors demonstrated relatively weak influences on the transport
      processes. The results obtained from the classification of Pb per the potential
      migration index (PMI) approximated those obtained from fuzzy clustering, and the
      results of entropy analyses were consistent with those of fuzzy clustering. Thus,
      the methods upon which the proposed model is based are suitable for predicting
      the migration capacity of Pb in ore during the mining of ionic rare earth
      minerals.

PMID- 30212735
TI  - Distribution of polybrominated diphenyl ethers (PBDEs) in feather and muscle of
      the birds of prey from Beijing, China.
AB  - Polybrominated diphenyl ethers (PBDEs) in the feather and muscle of common
      kestrels (Falco tinnunculus), eagle owls (Bubo bubo) and little owls (Athene
      noctua) collected from Beijing, China were investigated. The concentrations of
      ?23PBDEs in the muscle and feather of all the birds of prey ranged from 46 to
      7.77 * 104 ng/g lipid weight (lw; median 241 ng/g lw) and 1.50-191 ng/g dry
      weight (dw; median 21.1 ng/g dw), respectively. Higher brominated congeners,
      e.g., BDE-209, -153, -207 and -196 were the dominant congeners in both feather
      and muscle. However, the concentrations of lower brominated congeners in feather
      were significantly correlated with those in muscle (p < 0.05), which suggested
      that feather could efficiently reflect lower brominated BDEs in the internal
      tissue of birds of prey. The calculated hazard quotients (HQs) > 10 in common
      kestrel and little owl suggested that the high levels of PBDEs posed potentially
      high risk to some birds of prey living in Beijing area.

PMID- 30212736
TI  - A wavelet gradient sparsity based algorithm for reconstruction of reduced-view
      tomography datasets obtained with a monochromatic synchrotron-based X-ray source.
AB  - High-resolution synchrotron computed tomography (CT) is very helpful in the
      diagnosis and monitor of chronic diseases including osteoporosis. Osteoporosis is
      characterized by low bone mass and cortical bone porosity best imaged with CT.
      Synchrotron CT requires a large number of angular projections to reconstruct
      images with high resolution for detailed and accurate diagnosis. However, this
      poses great risks and challenges for serial in-vivo human and animal imaging due
      to a large amount of X-ray radiation dose required that can damage living
      specimens. Also, longer scan times are associated with increased risk of specimen
      movement and motion artifact in the reconstructed images. We developed a wavelet
      gradient sparsity based algorithm to be utilized as a synchrotron tomography
      reconstruction technique allowing accurate reconstruction of cortical bone
      porosity assessed for in-vivo preclinical study which significantly reduces the
      radiation dose and scan time required while maintaining satisfactory image
      resolution for diagnosis. The results of our study on a rat forelimb sample
      imaged in the Biomedical Imaging and Therapy Bending Magnet (BMIT-BM) beamline at
      the Canadian Light Source show that the proposed algorithm can produce
      satisfactory image quality with more than 50 percent X-ray dose reduction as
      indicated by both visual and quantitative-based performance.

PMID- 30212738
TI  - Iterative multi-path tracking for video and volume segmentation with sparse point
      supervision.
AB  - Recent machine learning strategies for segmentation tasks have shown great
      ability when trained on large pixel-wise annotated image datasets. It remains a
      major challenge however to aggregate such datasets, as the time and monetary cost
      associated with collecting extensive annotations is extremely high. This is
      particularly the case for generating precise pixel-wise annotations in video and
      volumetric image data. To this end, this work presents a novel framework to
      produce pixel-wise segmentations using minimal supervision. Our method relies on
      2D point supervision, whereby a single 2D location within an object of interest
      is provided on each image of the data. Our method then estimates the object
      appearance in a semi-supervised fashion by learning object-image-specific
      features and by using these in a semi-supervised learning framework. Our object
      model is then used in a graph-based optimization problem that takes into account
      all provided locations and the image data in order to infer the complete pixel
      wise segmentation. In practice, we solve this optimally as a tracking problem
      using a K-shortest path approach. Both the object model and segmentation are then
      refined iteratively to further improve the final segmentation. We show that by
      collecting 2D locations using a gaze tracker, our approach can provide state-of
      the-art segmentations on a range of objects and image modalities (video and 3D
      volumes), and that these can then be used to train supervised machine learning
      classifiers.

PMID- 30212737
TI  - Sizing up the cell cycle: systems and quantitative approaches in Chlamydomonas.
AB  - The unicellular green alga Chlamydomonas provides a simplified model for defining
      core cell cycle functions conserved in the green lineage and for understanding
      multiple fission, a common cell cycle variation found in many algae. Systems
      level approaches including a recent groundbreaking screen for conditional lethal
      cell cycle mutants and genome-wide transcriptome analyses are revealing the
      complex relationships among cell cycle regulators and helping define roles for
      CDKA/CDK1 and CDKB, the latter of which is unique to the green lineage and plays
      a central role in mitotic regulation. Genetic screens and quantitative single
      cell analyses have provided insight into cell-size control during multiple
      fission including the identification of a candidate 'sizer' protein. Quantitative
      single-cell tracking and modeling are promising approaches for gaining additional
      insight into regulation of cellular and subcellular scaling during the
      Chlamydomonas cell cycle.

PMID- 30212739
TI  - Exploring the intrinsic benefits of nursing preceptorship: A personal
      perspective.
AB  - Preceptorship is a strategy commonly used in nursing education. Its benefits have
      been reported in assisting nursing students and novice nurses with reality based
      knowledge, skill acquisition, confidence, and professional socialization. Though
      the benefits provided to the preceptor are under reported. This article aims to
      explore the intrinsic value seasoned nurses obtain through their participation in
      preceptorship in clinical practice. A personal perspective is examined using
      appreciative inquiry and reveals eight key themes which include: acknowledgement,
      preceptor-preceptee relationship/friendship, reciprocal learning, passion,
      satisfaction, helping, legacy and affirmation. Connections are then formed with
      the identified intrinsic values and the preceptor's commitment and desire to
      participate in preceptorship in clinical practice. Exploration of positive based
      personal experiences with preceptorship in clinical practice may help to retain
      and recruit preceptors for future preceptorship experiences, contribute to the
      growth and development of the preceptor role, and professional nursing practice.

PMID- 30212740
TI  - The association between restless legs syndrome and premotor symptoms of
      Parkinson's disease.
AB  - BACKGROUND: Previous studies regarding the association between restless legs
      syndrome (RLS) and Parkinson's disease (PD) have produced contradictory results.
      However, the time frame between them has varied across these studies, and also,
      the longitudinal trajectroy of RLS symptoms has not been considered. OBJECTIVE:
      To investigate if transient or continuous/recurrent RLS identified by
      questionnaire are associated with the premotor symptoms of PD. METHODS: The study
      population comprised 16,636 men in the Health Professional Follow-Up Study, who
      answered questions regarding RLS symptoms in both 2002 and 2008, and were not
      diagnosed with PD. Outcomes were self-reported constipation, possible REM sleep
      behavior disorder (pRBD) in 2012 and smell identification test score in 2014.
      RESULTS: RLS was associated with increased odds of constipation, but only
      continuous/recurrent RLS status was associated with higher odds of having pRBD.
      RLS was not significantly associated with olfactory scores. CONCLUSION: In this
      large-scale longitudinal study, we found moderate associations between the
      presence of RLS and increased odds of having constipation and pRBD.

PMID- 30212741
TI  - Microcystin-leucine arginine (MC-LR) induced inflammatory response in bovine
      sertoli cell via TLR4/NF-kB signaling pathway.
AB  - Sertoli cells were treated with 0, 20, 40, 60 and 80 MUg/L of MC-LR to
      investigate its toxic effects, mechanism of action and immune response of the
      cells. Our results revealed that treatment containing 20 MUg/L of MC-LR was non
      toxic to the cells. Treatments containing 40, 60 and 80 MUg/L of MC-LR reduced
      the cell viability, induced nuclear morphological changes and downregulated the
      blood-testis barrier constituent proteins within 48 h after treatment. The toll
      like receptor 4 (TLR4) and nuclear factor-kappaB (NF-kB) were activated and
      significantly (P < 0.05) upregulated in cells treated with 40, 60 and 80 MUg/L of
      MC-LR compared to the control. The pro-inflammatory cytokines were upregulated
      within 48 h after treatment. However commencing from 72 h, upregulation of anti
      inflammatory cytokines and expression of blood-testis barrier constituent
      proteins was observed. This study indicates that MC-LR induced inflammatory
      response in bovine Sertoli cell via activation of TLR4/NF-kB signaling pathway.

PMID- 30212742
TI  - Quantitative assessment of HR and NHEJ activities via CRISPR/Cas9-induced
      oligodeoxynucleotide-mediated DSB repair.
AB  - Homologous recombination (HR) and non-homologous end joining (NHEJ) are the two
      major mechanisms for the repair of DNA double-strand breaks (DSBs) in eukaryotic
      cells. Previously, we designed an assay for detecting NHEJ activity by using
      clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated protein 9 (Cas9) system, however, this approach cannot be used to
      predict the activity of HR repair. Hence, we developed a novel method that is
      capable of quantitatively measuring both HR and NHEJ activities via CRISPR/Cas9
      induced oligodeoxynucleotide (ODN)-mediated DSB repair. In the present
      experimental procedures, the CRISPR/Cas9 plasmid was cotransfected with single
      stranded ODN (ssODN) or blunt-ended double-stranded ODN (dsODN), both of which
      harbored a unique marker sequence. After the induction of site-specific DSBs by
      CRISPR/Cas9 system, the ssODN, functioned as the donor template for HR repair,
      could insert the marker sequence into the DSB sites, while the dsODN was embedded
      in the DSB sites through NHEJ pathway. Next, by means of PCR analysis using a
      specific primer for the marker sequence and the primers that flank the DSB sites,
      the relative amount of integrated marker sequence in the genomic DNA could be
      quantitatively determined. The correlation between the marker sequence abundance
      and the HR and NHEJ activities was confirmed by using the selective HR and NHEJ
      inhibitors. This accessible and rapid quantitative assay for HR and NHEJ
      activities might be useful for the future research of the DSB repair mechanisms.

PMID- 30212743
TI  - Exome sequencing in adult neurology practice: Challenges and rewards in a mixed
      resource setting.
AB  - OBJECTIVE: To share the experience of next-generation sequencing (NGS) in
      delineating molecular basis of neuro-genetic disorders in adults of Indian
      origin. PATIENTS AND METHODS: Adults (aged >=18 years) evaluated in a single
      neurology unit at a tertiary-care teaching hospital between August 2014 and
      September 2016, underwent NGS for (i) sporadic occurrence of neurological
      disorder where an extensive search did not reveal an acquired cause or (ii)
      familial or sporadic, uncommon, seemingly genetic disorder where single monogenic
      cause could not be ascertained based on phenotype. Presence of pathogenic/ likely
      pathogenic variants, novel genetic variants, and novel phenotype associations
      were noted. RESULTS: Clinical phenotypes included: neuromuscular (n = 14),
      extrapyramidal (n = 8), ataxia (n = 7), leukoencephalopathy (n = 6), spastic
      paraplegia (n = 5), stroke (n = 4), progressive myoclonic epilepsy (n = 1) and
      epilepsy with developmental delay (n = 1). Fifty-eight variants were identified
      in 43 genes in 34 patients, that included 15 (25.9%) reported variants. Genetic
      diagnosis could be established in 14 (30.43%) subjects. Six probands (13%)
      harboured previously unreported variants in a clinically relevant gene. Nine
      probands harboured unreported variants in two or more different genes associated
      with the clinical phenotype. In three probands we noted novel associations
      between the phenotype and genetic variation. In all patients, genetic diagnosis
      impacted treatment and prognostication. CONCLUSIONS: We present data of NGS in
      adults with suspected neuro-genetic disorders from India and this is the first
      report of its kind. It sets a platform for further basic science research to
      validate 'novel' variants and those of 'uncertain significance' as pathogenic or
      otherwise with specific reference to Indian ethnicity.

PMID- 30212744
TI  - Towards a repository of synthetic electrograms for atrial activation detection in
      atrial fibrillation.
AB  - BACKGROUND: Recently, the analysis of the spatio-temporal behavior of atrial
      fibrillation activation patterns has been widely investigated with the aim to
      better understand the arrhythmia implications on the heart electrical activity.
      Most of the proposed techniques are based on atrial activation timing detections.
      Unfortunately atrial activation timings are not easily recognizable on the
      electrograms (EGMs) and an approach to support the validation of such techniques
      is highly desirable. The aim of this study is to provide an effective workflow
      for the generation of synthetic unipolar atrial electrograms (SEGMs) in atrial
      fibrillation (AF) condition and with different levels of noise. METHOD: Real EGMs
      signals were obtained from a dataset of 6 subjects that underwent ablation. Each
      SEGM was obtained by modeling the three principal components of an EGM starting
      from real signals: atrial far-field (Afar), atrial near-field (Anear) and the
      ventricular far-field (Vfar). Afar was generated using an autoregressive model
      applied on segments from real EGMs not characterized by ventricular or atrial
      activations; Anear and Vfar were extracted directly from the real signals. A
      Gamma distribution and an atrio-ventricular node model were used to locate both
      Anear and Vfar on Afar, respectively. Three electrophysiologists with different
      levels of expertise evaluated the realism of the SEGMs on a set of 100 randomly
      selected signals including 50 EGMs and 50 SEGMs. Analysis was repeated by the
      three experts on a subset of 21 signals. RESULTS: The time required to generate
      the synthetic EGMs was less than 1 min once annotated EGMs are available. The
      cardiologists succeeded in distinguishing real from synthetic EGMs in 45%, 43%
      and 35% of the signals, respectively. By repeating the evaluation, 28%, 0% and
      48% of signals were classified differently, including 67%, 52% and 36% of correct
      classifications. CONCLUSION: The proposed approach proved to be effective in
      producing SEGMs which are difficult to distinguish from real EGMs. This study
      provides a tool for realistic SEGM generation from real EGMs in AF condition with
      different levels of noise and at different AF rates. The tool may be easily
      adopted to obtain SEGMs in different arrhythmic conditions. SEGMs generated in
      this study are shared with the scientific community as a first step towards a
      repository of synthetic and real atrial signals supporting the benchmarking of
      new approaches to investigate AF.

PMID- 30212745
TI  - Bone remodelling of the humerus after a resurfacing and a stemless shoulder
      arthroplasty.
AB  - BACKGROUND: New implant designs, such as resurfacing and stemless implants, have
      been developed to improve the long-term outcomes of the shoulder arthroplasty.
      However, it is not yet fully understood if their influence on the bone load
      distribution can compromise the long-term stability of the implant due to bone
      mass changes. Using three-dimensional finite element models, the aim of the
      present study was to analyse the bone remodelling process of the humerus after
      the introduction of resurfacing and stemless implants based on the Global C.A.P.
      and Sidus Stem-Free designs, respectively. METHODS: The 3D geometric model of the
      humerus was generated from the CT data of the Visible Human Project and the
      resurfacing and stemless implants were modelled in Solidworks. Considering a
      native humerus model, a humerus model with the resurfacing implant, and a humerus
      model with the stemless implant, three finite element models were developed in
      Abaqus. Bone remodelling simulations were performed considering healthy and poor
      bone quality conditions. The loading condition considered comprised 6 load cases
      of standard shoulder movements, including muscle and joint reaction forces
      estimated by a multibody model of the upper limb. FINDINGS: The results showed
      similar levels of bone resorption for the resurfacing and stemless implants for
      common humeral regions. The regions underneath the head of the resurfacing
      implant, unique to this design, showed the largest bone loss. For both implants,
      bone resorption was more pronounced for the poor bone quality condition than for
      the healthy bone quality condition. INTERPRETATION: The stemless implant lost
      less density at the fixation site, which might suggest that these implants may be
      better supported in the long-term than the resurfacing implants. However, further
      investigation is necessary to allow definite recommendations.

PMID- 30212747
TI  - The relationship between perceived competence and perceived workplace bullying
      among registered nurses: A cross sectional survey.
AB  - BACKGROUND: Workplace bullying is one of the most prevalent work-related
      psychological and physical issues in health care facilities. Workplace bullying
      has detrimental effects not only on the bullied person/persons but also on health
      care facilities and care quality and patient safety. AIMS: To examine the
      prevalence of workplace bullying and the relationship between workplace bullying
      and perceived competence among Jordanian registered nurses working in private
      hospitals DESIGN: A cross-sectional survey study. SETTING: Data were collected
      from registered nurses working in seven private hospitals in the Capital of
      Amman. PARTICIPANTS: Participants were 269 registered nurses who had a minimum of
      a bachelor degree, passed the hospital's competency nursing examinations, able to
      read and understand English, and were able and willing to complete the survey.
      METHODS: The Negative Act Questionnaire-Revised, and Nurse Professional
      Competence scale were used for data collection. Multiple linear regression
      analysis was conducted to assess predictors of greater reporting of perceived
      workplace bullying. FINDINGS: Almost 43% of the participants perceived themselves
      to be victims of severe workplace bullying while more than 31% perceived
      themselves to be victims of occasional workplace bullying. Person-related
      bullying was the most frequently reported type of workplace bullying followed by
      work-related bullying. Age, gender, and sum score on Nurse Professional
      Competence scale explained significant amount of variance in perceived workplace
      bullying. CONCLUSION: The majority of Jordanian nurses working in private
      hospitals perceive themselves as victims of either occasional or severe workplace
      bullying. Amongst all related variables, perceived competence is the most
      significant predictor of perceived workplace bullying.

PMID- 30212746
TI  - Cortical regions supporting reading comprehension skill for single words and
      discourse.
AB  - A substantial amount of variation in reading comprehension skill is explained by
      listening comprehension skill, suggesting tight links between printed and spoken
      discourse processing. In addition, both word level (e.g., vocabulary) and
      discourse-level sub-skills (e.g., inference-making) support overall
      comprehension. However, while these contributions to variation in comprehension
      skill have been well-studied behaviorally, the underlying neurobiological basis
      of these relationships is less well understood. In order to examine the neural
      bases of individual differences in reading comprehension as a function of input
      modality and processing level, we examined functional neural activation to both
      spoken and printed single words and passages in adolescents with a range of
      comprehension skill. Data driven Partial Least Squares Correlation (PLSC)
      analyses revealed that comprehension skill was positively related to activation
      in a number of regions associated with discourse comprehension and negatively
      related to activation in regions associated with executive function and memory
      across processing levels and input modalities.

PMID- 30212748
TI  - Relationships between family resilience, breast cancer survivors' individual
      resilience, and caregiver burden: A cross-sectional study.
AB  - BACKGROUND: Caregivers of breast cancer survivors experience various types of
      burden, which in turn is linked to patients' physical and psychological status.
      Family resilience might be able to decrease caregiver burden and facilitate
      survivors' individual resilience, and individual resilience might be related to
      caregiver burden. Nevertheless, these relationships have not yet been confirmed.
      OBJECTIVE: To determine the relationships between family resilience, breast
      cancer survivors' resilience, and principal caregivers' caregiver burden, as well
      as determine whether breast cancer survivors' individual resilience plays a
      mediating role in the relationship between family resilience and caregiver
      burden. DESIGN: Cross-sectional study design. SETTING: The comprehensive cancer
      center of a public hospital in Shandong Province, China. PARTICIPANTS: The sample
      comprised 108 dyads of early-stage breast cancer survivors and their principal
      caregivers. METHODS: The principal caregivers completed the Shortened Chinese
      Version of the Family Resilience Assessment Scale and the Chinese Version of the
      Zarit Caregiver Burden Interview, while the breast cancer survivors completed the
      10-item Chinese version of the Connor-Davidson Resilience Scale and provided
      their sociodemographic information. The mediating effect of individual resilience
      was estimated using the bootstrap method via IBM SPSS Amos 21.0. RESULTS:
      Caregiver burden was significantly negatively associated with both family
      resilience and breast cancer survivors' individual resilience (both p < .01).
      Furthermore, individual resilience mediated the relationship between family
      resilience and caregiver burden (b = -0.052; 95% confidence interval: -.412, 
      .036). CONCLUSIONS: The findings suggest that both family resilience and breast
      cancer survivors' individual resilience may ease caregiver burden among the
      principal caregivers of breast cancer survivors, and family resilience tends to
      promote the survivors' individual resilience. Therefore, family resilience and
      survivors' individual resilience should be enhanced for breast cancer survivors
      and their family to ease the principal caregivers' caregiver burden.

PMID- 30212749
TI  - The respiratory effect of tracheal gas insufflation (TGI) on tracheostomized
      spontaneously breathing ICU patients.

PMID- 30212750
TI  - American ginseng microbial metabolites attenuate DSS-induced colitis and
      abdominal pain.
AB  - Inflammatory bowel disease (IBD) is a significant public health problem in the
      United States. Abdominal pain is a major complaint among individuals with IBD.
      Successful IBD management not only controls enteric inflammation, but also
      reduces abdominal discomfort. Recently, increased attention has been focused on
      alternative strategies for IBD management. HPLC/Q-TOF-MS analysis was employed to
      evaluate the intestinal microbiome's biotransformation of parent American ginseng
      compounds into their metabolites. Using a DSS mouse model, the effects of
      American ginseng microbial metabolites on chemically induced colitis was
      investigated with disease activity index and histological assessment. Expressions
      of inflammatory cytokines were determined using real-time PCR and ELISA.
      Abdominal pain was evaluated using the von Frey filament test. After the gut
      microbiome's biotransformation, the major metabolites were found to be the
      compound K and ginsenoside Rg3. Compared with the DSS animal group, American
      ginseng treatment significantly attenuated experimental colitis, as supported by
      the histological assessment. The enteric microbiome-derived metabolites of
      ginseng significantly attenuated the abdominal pain. American ginseng treatment
      significantly reduced gut inflammation, consistent with pro-inflammatory cytokine
      level changes. The gut microbial metabolite compound K showed significant anti
      inflammatory effects even at low concentrations, compared to its parent
      ginsenoside Rb1. American ginseng intestinal microbial metabolites significantly
      reduced chemically-induced colitis and abdominal pain, as mediated by the
      inhibition of pro-inflammatory cytokine expression. Intestinal microbial
      metabolism plays a critical role in American ginseng mediated colitis management.

PMID- 30212751
TI  - Suppression of mouse miRNA-222-3p in response to Echinococcus multilocularis
      infection.
AB  - During Echinococcus multilocularis infection, serum miR-222-3p is dramatically
      downregulated, but its role is yet to be established. Here the expression of miR
      222-3p in the spleen of infected mice was shown to be significantly decreased in
      response to parasite infection (p < 0.05). Using RAW264.7 macrophages, it was
      further demonstrated that E. multilocularis crude antigens significantly
      inhibited miR-222-3p expression (p < 0.01). In macrophages transfected with a miR
      222-3p inhibitor, NO secretion was moderately decreased compared with the control
      (p < 0.05). Although all the pro- and anti-inflammatory cytokine genes tested
      kept constant in expression, four key genes involved in the LPS/TLR4 signaling
      pathway were significantly down- or up-regulated in transfected cells (p < 0.05),
      including CD14, TLR4, TICAM2 and AP-1. These results suggest that downregulated
      miR-222-3p is capable of modulating macrophage immune functions, possibly
      contributing to the pathogenesis during E. multilocularis infection.

PMID- 30212752
TI  - Direct and indirect influences of virus-insect vector-plant interactions on non
      circulative, semi-persistent virus transmission.
AB  - Plant viruses that are transmitted in a non-circulative, semi-persistent (NCSP)
      manner have determinants on, and/or accessories to, their capsids that facilitate
      virion binding to specific retention sites in their insect vectors. Bilateral
      interactions and interactions occurring at the nexus of all three partners
      (virus, vector and plant) also contribute to transmission by influencing virus
      acquisition and inoculation. Vector feeding behavior lies at the core of this
      trio of virus transmission processes (retention-acquisition-inoculation), but
      transmission may also be mediated by virus infection-triggered and/or vector
      feeding-triggered plant cues that influence behavioral responses such as vector
      attraction, deterrence and dispersal. Insights into the multiphasic interactions
      and coordinated processes will lead to a better understanding of the mechanisms
      of NCSP transmission.

PMID- 30212753
TI  - It's all in your head: Expectations create illusory perception in a dual-task
      setup.
AB  - Predictions about the world can guide our perception and action, but they can
      also misguide us. We developed novel dual-task setups where the participants are
      occupied by a primary task and are from time to time queried about the phenomenal
      contents of the auxiliary task. We show that "hallucinating" the presence of an
      actually absent stimulus is not an exception, but a common phenomenon (more than
      90% of participants experienced illusory objects at least once). Additionally, in
      experiment 1 we found a negative correlation between the amount of illusory
      perceptions and the Autism Spectrum Quotient score. People who scored higher on
      the questionnaire, were less likely to experience illusory objects. Finally, we
      observed no effect of spatial attention on expectation-based illusory presence of
      an object. More generally our results demonstrate that expectations misguide
      perception when attention is diverted to another task.

PMID- 30212754
TI  - Inducing dissociation and schizotypal experiences through "vision-deforming"
      glasses.
AB  - Derealization, depersonalization and schizotypal experiences are described as
      separate concepts but they can be hard to distinguish. One way to show the
      uniqueness of these concepts is by showing a dissociation between these
      experiences. The aim of this study was to experimentally induce derealization
      without inducing depersonalization or schizotypal experiences. Healthy
      participants watched a neutral video in one of four conditions: (1) with
      stroboscopic light, (2) while wearing deforming glasses, (3) with stroboscopic
      light and while wearing "vision deforming glasses" or (4) without any
      manipulation. The results show that the "vision deforming" glasses induced
      derealization without inducing depersonalization but not without inducing
      schizotypal experiences. The stroboscopic light showed no significant effect, nor
      was there a significant interaction between the stroboscopic light and the
      deforming glasses. The results indicate that using "vision deforming" glasses as
      a manipulation method can show a single dissociation between derealization and
      depersonalization but cannot dissociate derealization from state schizotypy. This
      association between derealization and schizotypal experiences might be helpful in
      understanding the high comorbidity rate between dissociative disorders and
      schizophrenia spectrum disorders.

PMID- 30212755
TI  - Examining the role of youth empowerment in preventing adolescence obesity in low
      income communities.
AB  - INTRODUCTION: Youth empowerment programs have increasingly gained attention in
      public health as emphasis shifts on children and adolescents as decision makers
      in their health and well-being. Adolescence obesity is among the public health
      concerns that require more active engagement at individual and community level
      while empowering adolescents to take charge of their own health. This study
      examines the influence of youth empowerment on nutritional and physical activity
      factors associated with adolescence obesity. METHODS: Data were gathered through
      a self-administered survey among adolescents (N = 410) ages 11-15 years in three
      U.S. States - Kansas, Ohio and South Dakota. RESULTS: Findings show that youth
      empowerment significantly influences adolescents' self-efficacy, perceptions for
      healthy food choice, healthy eating, attitudes towards physical activity and the
      overall motivation for health. Gender differences exist in adolescents' self
      efficacy for physical activity whereas ethnicity played a role in perceived youth
      empowerment and perceived barriers to healthy eating. Age was also a significant
      contributor in efficacy for healthy food choice and perception of healthy food
      availability. CONCLUSIONS: This study suggests more focus on youth empowerment in
      interventions that seek to reduce obesity and improve adolescents' overall health
      by creating environments where they can play a more active decision-making role.
      With empowerment, adolescents are more likely to be motivated to adopt healthier
      dietary habits and engage more in physical activity. Further research would
      establish the impact of youth empowerment on obesity reduction and other public
      health problems that impact children across ages.

PMID- 30212757
TI  - Type 1 narcolepsy in anti-Hu antibodies mediated encephalitis: a case report.

PMID- 30212756
TI  - Real-time predictors of smoking among sexual minority and heterosexual young
      adults: An ecological momentary assessment study.
AB  - BACKGROUND: Sexual minority young adults have higher smoking rates than the
      general young adult population, but reasons for this disparity are poorly
      understood. The current study aimed to: 1) identify real-time predictors of
      smoking among sexual minority and heterosexual smokers and 2) examine between
      group differences in these predictors. METHODS: We conducted an ecological
      momentary assessment (EMA) study in the San Francisco Bay Area, California in
      2016-2017. Data from 84 young adult smokers (44% identified as sexual minority,
      including 29 bisexual and 8 gay/lesbian) with 6498 EMA assessments were analyzed.
      Both internal and external predictors and interaction terms between each
      predictor and sexual group were examined using generalized estimating equation
      models. RESULTS: Common correlates of smoking were found for both groups (e.g.,
      craving, absence of smoking bans, presence of other smokers, outside location,
      and seeing triggers). Unique factors for sexual minority smokers were being at a
      bar (aOR = 1.75, 95% CI = 1.06-2.90) and the number of other smokers present (aOR
      = 1.12, 95%CI = 1.04-1.20), while the presence of a smoking family member reduced
      the odds of smoking in this group (aOR = 0.13, 95%CI = 0.02-0.85). In interaction
      models, the number of other smokers exerted a greater influence on sexual
      minority participants compared to their heterosexual counterparts (aOR = 1.10,
      95%CI = 1.01-1.20), while craving (aOR = 0.84, 95%CI = 0.75-0.93) and presence of
      a smoking family member (aOR = 0.11, 95%CI = 0.01-0.82) had weaker influences.
      CONCLUSIONS: Our study highlights unique situational factors associated with
      smoking among sexual minority young adults and differences in these factors by
      sexual identity. Future interventions targeting sexual minorities should address
      bar attendance and specific triggers.

PMID- 30212758
TI  - "We were on our own": Mothers' experiences navigating the fragmented system of
      professional care for autism.
AB  - Autism is a developmental disorder that emerges in early childhood. Treatments
      for autism span a wide variety of professionals and paraprofessionals in the
      medical and educational realms. This article draws on data from a survey of 620
      parents of autistic children, including 385 written narratives, to examine the
      experiences of mothers as they engage with this fragmented system of professional
      care for children with autism. Findings suggest that engagement with treatments
      sent families into a complex and confusing universe of diagnosis and treatment.
      The fragmentation of autism's professional jurisdiction between the medical and
      educational systems meant that mothers struggled to find comprehensive
      professional care that met the standards recommended by leading medical research
      organizations. Many mothers found it necessary to reduce their workforce
      participation in order to obtain and maintain their children's treatment regimes,
      a phenomenon that transcended social class. However, the consequences of reducing
      work had differential impacts on families. While married and high socioeconomic
      status mothers were more insulated from the potential negative effects of losing
      one partner's income, single and low SES mothers experienced greater precarity.
      These findings connect the structure and arrangement of professional
      jurisdictions to the experiences of parents, suggesting ways that the
      fragmentation of professional care for autism can have negative impacts for
      women, single mothers, and low SES families.

PMID- 30212759
TI  - OsJMJ703, a rice histone demethylase gene, plays key roles in plant development
      and responds to drought stress.
AB  - JmjC-domain-containing (JmjC) protein, an important kind of histone demethylase
      in plants, plays key roles in multiple growth and development processes and in
      adversity resistance. In this study, we found that OsJMJ703, a known histone
      demethylase, is expressed in various tissues. Furthermore, over-expression of
      OsJMJ703 influenced the type of rice panicle, and knock-down of the expression of
      OsJMJ703 showed an earlier flowering time in rice. In addition, OsJMJ703 is
      involved in abiotic stress. Transgenic rice of over-expressing OsJMJ703 is
      sensitive to drought stress, whereas knocking down OsJMJ703 enhances the
      tolerance to drought stress. This study provides a theoretical basis of the
      biological function of JmjC protein and further promotes the study of drought
      resistance.

PMID- 30212761
TI  - Application of biochar to soils may result in plant contamination and human
      cancer risk due to exposure of polycyclic aromatic hydrocarbons.
AB  - Biochars are added to soil to improve agronomic yield. This greenhouse- and field
      scale study evaluated polycyclic aromatic hydrocarbon (PAH) contamination in 35
      commercial and laboratory-produced biochars, and assessed the effects of biochar
      amendment of soils on PAH accumulation in vegetables and the risk for cancer. The
      total and bioavailable PAH concentrations in biochars varied from 638 to 12,347
      MUg/kg and from below the detection limit (BDL) to 2792 MUg/kg, respectively. PAH
      formation in biochars decreased with increasing production temperature (350-650 
      degrees C). Root exudates enhanced PAH release from biochars. The total PAH
      concentrations in eight edible vegetables growing in biochar-amended soil varied
      according to biochar and vegetables type from BDL to 565 MUg/kg. A health risk
      assessment framework was integrated with the benzo[a]pyrene toxic equivalency
      quotient and the incremental lifetime cancer risk (ILCR) to estimate the exposure
      risk for human beings via ingestion of PAH-contaminated vegetables. The total
      ILCR for adults was above 10-6, which suggests a risk to human health from direct
      exposure to PAHs in vegetables grown in biochar-amended soil. These results
      demonstrate that biochar application may lead to contamination of plants with
      PAHs, which represents a risk to human health. The PAH levels in biochars
      produced using different conditions and/or feedstocks need to be evaluated and
      biochars should be pretreated to remove PAHs before their large-scale agronomic
      application.

PMID- 30212760
TI  - Ammonium mitigates Cd toxicity in rice (Oryza sativa) via putrescine-dependent
      alterations of cell wall composition.
AB  - In plants, different forms of nitrogen (NO3- or NH4+) affect nutrient uptake and
      environmental stress responses. In the present study, we tested whether NO3- and
      NH4+ affect the ability of rice (Oryza sativa) to tolerate the toxic heavy metal
      cadmium (Cd). Compared with NO3-, NH4+ treatment significantly increased
      chlorophyll contents and reduced Cd2+ levels in rice cultivars Nipponbare
      (japonica) and Kasalath (indica) grown in 0.2 mM Cd2+. NH4+ significantly reduced
      the pectin and hemicellulose contents and inhibited the pectin methylesterase
      (PME) activity in rice roots, thereby reducing the negative charges in the cell
      wall and decreasing the accumulation of Cd2+ in roots. In addition, NH4+ reduced
      the absorption and root-to-shoot translocation of Cd2+ by decreasing the
      expression of OsHMA2 and OsNramp5 in the root. Levels of the signaling molecule
      putrescine were significantly higher in the roots of both rice cultivars provided
      with NH4+ compared with NO3-. The addition of putrescine reduced Cd2+ contents in
      both rice cultivars and increased the chlorophyll content in shoots by reducing
      root cell wall pectin and hemicellulose contents, inhibiting PME activity and
      suppressing the expression of OsHMA2 and OsNramp5 in the root. Taken together,
      these results indicate that NH4+ treatment alleviated Cd toxicity, enabling rice
      to withstand the noxious effects of Cd by modifying the cell wall Cd-binding
      capacity due to alterations of pectin and hemicellulose contents and Cd
      transport, processes induced by increasing putrescine levels. Our findings
      suggest methods to decrease Cd accumulation in rice by applying NH4+ fertilizers.

PMID- 30212762
TI  - Multivariate analysis of genome-wide data to identify potential pleiotropic genes
      for five major psychiatric disorders using MetaCCA.
AB  - BACKGROUND: Genome-wide association studies have been extensively applied in
      identifying SNP associated with major psychiatric disorders. However, the SNPs
      identified by the prevailing univariate approach only explain a small percentage
      of the genetic variance of traits, and the extensive data have shown the major
      psychiatric disorders have common biological mechanisms and the overlapping
      pathophysiological pathways. METHODS: We applied the genetic pleiotropy-informed
      metaCCA method on summary statistics data from the Psychiatric Genomics
      Consortium Cross-Disorder Group to examine the overlapping genetic relations
      between the five major psychiatric disorders. Furthermore, to refine all genes,
      we performed gene-based association analyses for the five disorders respectively
      using VEGAS2. Gene enrichment analysis was applied to explore the potential
      functional significance of the identified genes. RESULTS: After metaCCA analysis,
      1147 SNPs reached the Bonferroni corrected threshold (p < 1.06 * 10-6) in the
      univariate SNP-multivariate phenotype analysis, and 246 genes with a significance
      threshold (p < 3.85 * 10-6) were identified as potentially pleiotropic genes in
      the multivariate SNP-multivariate phenotype analysis. By screening the results of
      gene-based p-values, we identified 37 putative pleiotropic genes which achieved
      significance threshold in metaCCA analyses and were also associated with at least
      one disorder in the VEGAS2 analyses. LIMITATIONS: Alternative approaches and
      experimental studies may be applied to check whether novel genes could still be
      identified/substantiated with these methods. CONCLUSIONS: The metaCCA method
      identified novel variants associated with psychiatric disorders by effectively
      incorporating information from different GWAS datasets. Our analyses may provide
      insights for some common therapeutic approaches of these five major psychiatric
      disorders based on the pleiotropic genes and common mechanisms identified.

PMID- 30212763
TI  - Design, synthesis, and biological evaluations of phenylpropiolic acid derivatives
      as novel GPR40 agonists.
AB  - GPR40, also known as free fatty acid receptor 1 (FFAR1), is a member of G protein
      coupled receptors (GPCR) family and has emerged as an attractive target for the
      treatment of type 2 diabetes mellitus. So far, most of the synthetic GPR40
      agonists, including several drug candidates discontinued in clinical trials, were
      derived from the phenylpropionic acid scaffold. For discovering novel GPR40
      agonists with diverse chemical structures, a series of phenylpropiolic acid
      derivatives were designed, synthesized, and evaluated under a battery of
      bioassays. Compound 9, the most potent compound in this series, exhibited
      submicromolar agonist activity and similar agonistic efficacy compared to that of
      TAK-875. In addition, compound 9 was able to dose-dependently amplify glucose
      stimulated insulin secretion (GSIS) in pancreatic beta-cell line MIN6, which
      could be reversed by a selective GPR40 antagonist GW1100. In addition, compound 9
      was found to have potent glucose-lowering effects during an oral glucose
      tolerance test in normal C57BL/6 mice.

PMID- 30212764
TI  - Defatted algal biomass as feedstock for short chain carboxylic acids and
      biohydrogen production in the biorefinery format.
AB  - The objective of the study was to evaluate the potential application of defatted
      algal biomass (DAB) residue as a resource for biobased product synthesis in the
      biorefinery framework. Acid-catalyzed pretreatment of DAB residue resulted in
      higher reducing sugars (RS) solubilization (0.26 g RS/g DAB) than corresponding
      base method (0.19 g RS/g DAB). Subsequently, resulting RS were acidogenically
      fermented for the production of Bio-H2 and short chain carboxylic acids
      (SCA)/volatile fatty acids (VFA) at varying redox conditions (pH: 6, 7 and 10).
      Biosystem with pH-6 resulted in higher SCA (0.54 g SCA/g RS) and Bio-H2
      production (0.83  l) followed by pH-10 (0.43 g SCA/g RS, 0.71  l) and pH-7 (0.27
      g SCA/g RS, 0.48  l). Higher SCA production in pH-6 system resulted in maximum
      acidification (23%). Algal biomass majorly derived from CO2 and its residues
      after lipids extraction accounted as major feedstock for acidogenic product
      synthesis. Evaluation of these studies using DAB residues offers sustainability
      to algal refineries on its entirety use.

PMID- 30212765
TI  - Oxadiazolone derivatives, new promising multi-target inhibitors against M.
      tuberculosis.
AB  - A set of 19 oxadiazolone (OX) derivatives have been investigated for their
      antimycobacterial activity against two pathogenic slow-growing mycobacteria,
      Mycobacterium marinum and Mycobacterium bovis BCG, and the avirulent
      Mycobacterium tuberculosis (M. tb) mc26230. The encouraging minimal inhibitory
      concentrations (MIC) values obtained prompted us to test them against virulent M.
      tb H37Rv growth either in broth medium or inside macrophages. The OX compounds
      displayed a diversity of action and were found to act either on extracellular M.
      tb growth only with moderated MIC50, or both intracellularly on infected
      macrophages as well as extracellularly on bacterial growth. Of interest, all OX
      derivatives exhibited very low toxicity towards host macrophages. Among the six
      potential OXs identified, HPOX, a selective inhibitor of extracellular M. tb
      growth, was selected and further used in a competitive labelling/enrichment assay
      against the activity-based probe Desthiobiotin-FP, in order to identify its
      putative target(s). This approach, combined with mass spectrometry, identified 18
      potential candidates, all being serine or cysteine enzymes involved in M. tb
      lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA, TesA,
      KasA and MetA have been reported as essential for in vitro growth of M. tb and/or
      its survival and persistence inside macrophages. Overall, our findings support
      the assumption that OX derivatives may represent a novel class of multi-target
      inhibitors leading to the arrest of M. tb growth through a cumulative inhibition
      of a large number of Ser- and Cys-containing enzymes involved in various
      important physiological processes.

PMID- 30212767
TI  - Retrospective analysis of children with myelin oligodendrocyte glycoprotein
      antibody-related disorders.
AB  - BACKGROUND: Knowledge has been expanding on myelin oligodendrocyte glycoprotein
      (MOG) antibody-associated central nervous system disorders. We delineate the
      clinical and paraclinical findings and outcome of our pediatric patients with MOG
      antibody seropositive disease. METHODS: We retrospectively analyzed the clinical
      presentation, cerebrospinal fluid findings, magnetic resonance imaging (MRI)
      studies, course and outcome of children seropositive for anti-MOG IgG. RESULTS:
      Total 20 children with neurological symptoms and serum anti-MOG IgG were
      identified from six centers in Turkey. Median age at onset was 9 years (mean 8.8
      +/- 5.0 years, range: 1.5-16.5 years). Final diagnoses were acute disseminated
      encephalomyelitis (ADEM) (n = 5), ADEM + optic neuritis (n = 4), neuromyelitis
      optica spectrum disorder (NMOSD) (n = 3), myelitis (n = 2), relapsing optic
      neuritis (n = 2), multiphasic DEM (n = 3), and unclassified relapsing
      demyelinating disease (n = 1). Seven/20 (35%) children experienced a single
      episode while 13/20 (65%) had a least one relapse during follow-up. On MRI,
      subcortical white matter, brainstem, and corpus callosum were preferentially
      involved regions. Full recovery was observed in 15/20 (75%) children. CONCLUSION:
      MOG autoimmunity in children has a wide clinical spectrum, tendency to relapse,
      and a favourable outcome compared with other relapsing demyelinating diseases.

PMID- 30212766
TI  - Neuroendocrine aspects of improving sleep in epilepsy.
AB  - Sleep plays an intricate role in epilepsy and can affect the frequency and
      occurrence of seizures. With nearly 35% of U.S. adults failing to obtain the
      recommended 7 h of sleep every night, understanding the complex relationship
      between sleep and epilepsy is of utmost relevance. Sleep deprivation is a common
      trigger of seizures in many persons with epilepsy and sleep patterns play a role
      in the occurrence of seizures. Some patients have their first seizure or repeated
      seizures after an "all-nighter" at college or after a long period of chronic
      sleep deprivation. The strength of the relationship between sleep and seizures
      varies between patients, but improving sleep and optimizing seizure control can
      have significant positive effects on the quality of life for all these patients.
      Research has shown that the changes in the brain's electrical and hormonal
      activity occurring during normal sleep-wake cycles can be linked to both sleep
      and seizure patterns. Many questions remain to be answered about sleep and
      epilepsy. How can sleep deprivation trigger an epileptic seizure? How do
      circadian and hormonal changes influence sleep pattern and seizure occurrence?
      Can hormones or sleeping pills help with sleep in epilepsy? In this article we
      discuss these and many other questions on sleep in epilepsy, with an emphasis on
      sleep architecture, hormone changes, mechanistic factors, and possible prevention
      strategies.

PMID- 30212769
TI  - Recurrent schilder's disease.
AB  - Schilder's disease is a rare and aggressive central nervous system demyelinating
      disorder that is typically monophasic and steroid responsive. Here, we present an
      unusual case of a teenager with Schilder's disease who was treated with
      corticosteroids and had a clinical and radiographic recurrence nearly one year
      after the initial presentation.

PMID- 30212768
TI  - Modified Functional Walking Categories and participation in people with multiple
      sclerosis.
AB  - BACKGROUND: Gait velocity influences the ability of a person to move in different
      outdoor or indoor contexts and has accordingly been classified through the
      Modified Functional Walking Categories (MFWC). Community ambulation in persons
      with multiple sclerosis (PwMS) may give information on their social and
      productive participation, as well as independence in household activities.
      OBJECTIVES: To investigate factors associated with walking and mobility
      restrictions as classified by the Modified Functional Walking Categories (MFWC)
      and analyze the influence of disease characteristics, demographical and walking
      factors on participation in PwMS. METHODS: 155 PwMS attending two rehabilitation
      center were evaluated. Community ambulation was classified with the MFWC;
      participation was measured with the Community Integration Questionnaire (CIQ).
      MFWC and statistically significant variables associated with CIQ score were
      entered in a multivariate logistic model to assess the multiple relationships.
      RESULTS: PwMS with a secondary progressive type of disease, longer disease
      duration and using walking aids were classified in the worse MFWC. Participation
      restrictions were more frequent in Limited Household (72.3%) and in Physiological
      Walkers (93.7%). The final multivariate model (p < 0.0001) showed that the use of
      a walking aid (OR = 2.59), being male (OR = 2.94) and older (OR = 1.06) increased
      the likelihood of having participation restrictions. The same variables predicted
      home participation; MFWC and age predicted productive participation while only
      age influenced social participation. CONCLUSIONS: Modified Functional Walking
      Categories were associated with type of disease, disease duration, disability
      level and type of walking aid. The best clinical predictor of participation
      restriction was walking aid while walking categories only predicted productive
      participation.

PMID- 30212770
TI  - Reactor performance and economic evaluation of anaerobic co-digestion of dairy
      manure with corn stover and tomato residues under liquid, hemi-solid, and solid
      state conditions.
AB  - Anaerobic co-digestion of tomato residues, dairy manure, and corn stover at
      ratios of 20:48:32, 40:36:24, and 60:24:16 (volatile solid basis) were compared
      for liquid anaerobic digestion (L-AD), hemi-solid state AD (HSS-AD), and solid
      state AD (SS-AD) systems. The highest methane yield (353.5 L/kg-VSadded) and
      volumetric methane productivity (24.5 m3methane/m3reactor volume) were both
      obtained with 20% tomato residues addition under L-AD and HSS-AD conditions,
      respectively. Total solid and feedstock mixing ratio affected the degradation of
      protein and lipids during AD, but not cellulose and hemicellulose. Economic
      analysis results indicated that capital and labor costs have the dominant effect
      on total investment. SS-AD of tomato residues, dairy manure, and corn stover at
      ratios of 20:48:32 (VS basis) has the highest net present value (2.6 million US$)
      and shortest payback period (10.1 year), which indicated SS-AD was financially
      attractive under analysis conditions.

PMID- 30212771
TI  - Evaluation of oleaginous eustigmatophycean microalgae as potential biorefinery
      feedstock for the production of palmitoleic acid and biodiesel.
AB  - This study aimed to evaluate the potential of six oleaginous eustigmatophytes for
      use as biorefinery feedstock for the co-production of palmitoleic acid (PA) and
      biodiesel under different initial nitrogen concentrations (INCs). Six
      eustigmatophytes were studied, the nitrogen deficiency strategy significantly
      stimulated the simultaneous hyper-accumulation of PA and lipids, and led to a
      desirable fatty acid profile (FAP), except in Vacuoliviride sp. and
      Nannochloropsis oculata. Particularly, Eustigmatos cf. polyphem exhibited great
      potential when supplied with 1 mM INC and yielded the highest PA (29.71% of dry
      weight (DW)) and lipid (72.01% of DW) contents, as their productivities increased
      to 96.26 and 232.79 mg/L/d, respectively. Furthermore, neutral lipids accounted
      for 91.82% of the total lipids and were rich in PA, and the favourable FAPs of
      C16-C18 (87.95%) and monounsaturated FAs (70.10%) ensured good biodiesel
      properties including the cetane number (55.69) and iodine value (92.81 gI2/100
      g), and all met the standard requirements.

PMID- 30212772
TI  - Drag reduction and shear-induced cells migration behavior of microalgae slurry in
      tube flow.
AB  - To optimize the designing of microalgae slurry pumping system and enhance the
      efficiency of microalgae products production, the flow characteristics of
      microalgae slurries (Chlorella pyrenoidosa) in tube flow were for the first time
      investigated combining experiments and numerical simulation. The drag reduction
      behavior of microalgae slurry in the fully developed laminar flow regime was
      studied. In addition, the transition Reynolds number of microalgae slurries from
      laminar flow to turbulent flow was about 1000-1300, which was similar to the
      expression of two-phase flow. To provide a further understanding of flow feature
      of microalgae slurries in tube, a two-phase mixture model was proposed by
      considering the heterogeneity of concentration due to the shear-induced
      microalgae cells migration behavior. Simulation results revealed that the
      heterogeneous distribution of concentration was affected by average velocity and
      volume fraction of microalgae slurries, significantly affecting the flow
      resistance and flow stability of microalgae slurry in the tube flow.

PMID- 30212773
TI  - Inhibition of anammox by sludge thermal hydrolysis and metagenomic insights.
AB  - Anaerobic ammonium oxidation (anammox) would be a feasible treatment method for
      thermal hydrolysis processed sidestream (THPS). Short-term study revealed that
      the 1/20 diluted THPS caused a 28% decrease of specific anammox activity. The MBR
      achieved a volumetric nitrogen loading rate of 3.64 kg/(m3.d) with undiluted
      regular sidestream (RS) fed, while the reactor crashed with 70% diluted THPS as
      feed. The ratio of produced NO3--N to consumed NH4+-N also decreased compared
      with RS feeding. Candidatus brocadia was the major anammox bacteria species with
      the average abundance of 33.3% (synthetic wastewater), 6.42% (RS) and 2.51%
      (THPS). The abundances of metagenome bins for dissimilatory nitrate reduction to
      ammonium (DNRA) increased in the system with THPS compared with RS. The reason
      for the inhibition of anammox by THPS could be the high content of organic carbon
      in THPS, which caused the over-population of heterotrophic bacteria, i.e. DNRA
      bacteria, leading to anammox bacteria washout.

PMID- 30212774
TI  - Lewis acid-catalyzed biphasic 2-methyltetrahydrofuran/H2O pretreatment of
      lignocelluloses to enhance cellulose enzymatic hydrolysis and lignin
      valorization.
AB  - Lewis acid-catalyzed pretreatment in a biphasic system consisting of bio-based
      solvent 2-methyltetrahydrofuran (2-MeTHF) and water for a highly integrated one
      pot catalytic transformation of lignocelluloses have been achieved. The aim of
      this work was to study the effects of different Lewis acid catalysts and
      pretreatment temperatures on the structural characteristics of precipitated
      lignin and enzymatic hydrolysis of the pretreated substrates, as well as the
      quantitative analysis of precipitates, solid residues, soluble carbohydrates and
      inhibitors. After the AlCl3-catalyzed biphasic 2-MeTHF/H2O pretreatment at 180 
      degrees C, its maximum cellulose conversion rate was enhanced by 7.4-fold as
      compared to the raw material. The precipitated lignin exhibited the
      representative structure, relatively low molecular weight and high purity for
      preparing value-added aromatic chemicals or renewable polymers. Overall, AlCl3
      catalyzed biphasic 2-MeTHF/H2O pretreatment may offer a promising approach for
      enhancing enzymatic hydrolysis and obtaining valorized lignin by-product.

PMID- 30212775
TI  - Psychrophilic anaerobic dynamic membrane bioreactor for domestic wastewater
      treatment: Effects of organic loading and sludge recycling.
AB  - Two upflow anaerobic dynamic membrane bioreactors (AnDMBRs) with and without
      sludge recycling were operated in parallel at varied organic loadings and
      psychrophilic temperature for domestic wastewater treatment. A 75 MUm nylon mesh,
      used as a supporting material, enabled quick and stable dynamic membrane
      formation. The AnDMBRs could operate continuously without relaxation at a high
      flux rate of 22.5 L/m2h; however, high organic loading accelerated the increasing
      rate of trans-membrane pressure (TMP). High chemical oxygen demand removal was
      achieved in both AnDMBRs with removal efficiencies of 70-90%. Sludge recycling
      enhanced the cross-flow velocity but negatively affected the effluent turbidity,
      sludge properties (particle size reduction and biopolymer release) and dynamic
      membrane filterability. Although increased organic loading enhanced biogas yield,
      the low biogas production was related to the dissolved methane loss in the
      effluent. Easy-operation, minimal maintenance and low-energy consumption makes
      the AnDMBR process cost-effective for practical wastewater treatment in temperate
      areas.

PMID- 30212776
TI  - Assessing the performance of a sequencing batch biofilm reactor bioaugmented with
      P. stutzeri strain XL-2 treating ammonium-rich wastewater.
AB  - Pseudomonas stutzeri XL-2, with the capability of heterotrophic nitrification
      aerobic denitrification and biofilm-forming, was applied in a sequencing batch
      biofilm reactor (SBBR) for bioaugmented treatment of ammonium-rich wastewater.
      The bioaugmented system SBBR 1 showed a rapid development of biofilm and
      relatively shorter time for biofilm hanging compared with the control system SBBR
      2 without strain XL-2 inoculation. At different NH4+-N loads of 100, 200 and 300
      mg/L, the effluent TN removal ratios ranged in 88.7-97.0%, 85.1-93.5% and 87.8
      92.5% respectively in SBBR 1, while only ranged in 77.4-85.4%, 77.1-84.3% and
      79.8-85.0% in SBBR 2. Less accumulation of NO2--N and NO3--N resulted in the
      better performance on TN removal in SBBR 1. Microbial community structure
      analysis revealed that strain XL-2 successfully proliferated in SBBR 1 and
      contributed to the less accumulation of NO2--N and NO3--N as well as biofilm
      formation.

PMID- 30212777
TI  - Optimizing culture conditions for heterotrophic-assisted photoautotrophic biofilm
      growth of Chlorella vulgaris to simultaneously improve microalgae biomass and
      lipid productivity.
AB  - In order to solve the technical bottleneck that the biomass yield and lipid
      accumulation cannot be increased simultaneously during microalgae growth, a
      heterotrophic-assisted photoautotrophic biofilm (HAPB) growth mode of Chlorella
      vulgaris was constructed. The light penetration capability of the microalgae
      biofilm formed through heterotrophic-assisted photoautotrophic growth was 64%
      stronger than that formed by photoautotrophic growth. Due to the different
      demands of autotrophic and heterotrophic growth of microalgae, the nutrient
      environment and growth conditions were optimized to fully utilize the advantages
      and potentials of the HAPB culture model. An optimized molar ratio of total
      inorganic carbon (CO2) to total organic carbon (glucose) (20:1) and a molar ratio
      of total carbon to total nitrogen (72:1) were obtained. The maximum specific
      growth rate of Chlorella vulgaris increased by 78% compared to that before
      optimization. Meanwhile, the lipid content and yield increased by 120% and 147%,
      respectively, up to 47.53% and 41.95 g m-2.

PMID- 30212778
TI  - On-site and ground-based remote sensing measurements of methane emissions from
      four biogas plants: A comparison study.
AB  - Methods for quantifying methane (CH4) emissions from biogas plants are needed, in
      order to ensure that emissions are within acceptable levels and to identify
      options for emission mitigation. Two emission measuring approaches were used at
      four biogas plants: an on-site approach, whereby emission sources were identified
      and subsequently quantified one at a time, and a ground-based remote sensing
      approach, which was applied to measure total CH4 emissions. The emissions were
      between 5.5 and 13.5 kg CH4 h-1 from the four plants, measured using ground-based
      remote sensing. Even though the measurements were performed on the same days at
      each facility, the sum of on-site emission rates varied between the remote
      sensing measurements (up to ~100%). Several factors may have caused this
      difference: emission sources not measured using an on-site approach and short
      time emission variation. On-site measurements showed that the majority of the
      emissions often occurred from just a few sources.

PMID- 30212779
TI  - Genetic manipulation of Escherichia coli central carbon metabolism for efficient
      production of fumaric acid.
AB  - Fumaric acid is one of the top 12-biomass building-block chemicals. In this
      study, we reported manipulation of E. coli central carbon metabolism with the aim
      to decrease the by-products and improve fumaric acid production. PEP-dependent
      glucose phosphotransferase system was replaced with a galactose translocation
      system to minimize the consumption of phosphoenolpyruvate. Engineering
      anaplerotic pathway (phosphoenolpyruvate carboxylase) was employed to
      redistribute carbon flux from glycolysis to Krebs cycle. Deletion of malate
      dehydrogenase and overexpression of acetyl-CoA synthase could decrease the
      byproducts malic acid and acetic acid. The combined strategies led to fumaric
      acid yield up to 1.53 g/g dry cell weight, a 50% increase compared with the
      parental strain. The result demonstrated that these genetic modifications were
      effective strategies for improving the production of fumaric acid and the
      engineered strain may serve a platform microbial cell factory for efficient
      production of fumaric acid or other dicarboxylic acids.

PMID- 30212780
TI  - Changing our minds: the neural bases of dynamic impression updating.
AB  - While a great deal of initial work in social neuroscience addressed the
      functional bases of our first impressions, our social evaluations of other people
      are anything but static. Just as our impressions can change, so too has our
      understanding of the neural underpinnings supporting this dynamic form of social
      learning. First, I review initial neuroimaging work on behavior-based impression
      updating, which observed that a distributed network of regions works in concert
      to revise trait representations in light of new behavioral information. Next, I
      discuss more recent research detailing how the updating process may be influenced
      by both bottom-up (e.g. experience) and top-down factors (e.g. motivation).
      Finally, I explore the contributions of more computational work studying similar
      processes via tasks that model social learning through repeated interactions and
      feedback-based reinforcement. Taken together, this work illustrates the expansion
      of our understanding of social impression formation, beyond static initial
      snapshots and towards a more dynamic process in which our representations of
      other people are continuously revised and reinterpreted in light of new
      information.

PMID- 30212781
TI  - Back muscle activity and sagittal spinal alignment during quadruped upper and
      lower extremity lift in young men with low back pain history.
AB  - BACKGROUND: Quadruped upper and lower extremity lift (QULEL) is performed for
      selective training of the lumbar multifidus muscle in patients with low back pain
      (LBP) or individuals with LBP history (LBPH). However, the activities of the back
      muscles and sagittal spinal alignment during QULEL are not clarified in
      individuals with LBPH. RESEARCH QUESTION: This study aimed to analyze the
      activities of the back muscles and sagittal spinal alignment during QULEL in
      young male with LBPH. METHODS: The study comprised 9 asymptomatic young men and 8
      young men with LBPH. The activities of the lumbar multifidus, latissimus dorsi
      and thoracic erector spinae, and lumbar erector spinae muscles were measured
      using surface electromyography. The flexion angles of the upper and lower
      thoracic spine, and extension angle of the lumbar spine were measured using a 6
      DF electromagnetic motion tracking system. The association with LBPH was
      investigated using multiple logistic regression analysis with a forward selection
      method, with the activities of the back muscles, sagittal spinal alignment, age,
      body height, and body weight as independent variables. RESULTS: Multiple logistic
      regression analysis (p = 0.0002) showed that the activity of the latissimus dorsi
      and thoracic erector spinae muscles in the side on which the lower extremity was
      lifted and body height were significant and independent determinants of LBPH, but
      other factors were not. SIGNIFICANCE: The results of this study suggest that the
      activity of the latissimus dorsi and thoracic erector spinae muscles increases
      while there are no decrease in activity of the lumbar multifidus muscle and
      excessive extension of the lumbar spine during QULEL in young men with LBPH.

PMID- 30212782
TI  - A kinematic and kinetic analysis of the hip and knee joints in patients with
      posterior tibialis tendon dysfunction; comparison with healthy age-matched
      controls.
AB  - BACKGROUND: The biomechanical abnormalities in patients with posterior tibial
      tendon dysfunction (PTTD) have been described, but few studies have investigated
      biomechanical chains of adjacent joints. Therefore, we examined the gait pattern
      of the lower extremity in subjects with PTTD, focusing on the hip and knee
      joints. METHODS: We compared 19 PTTD patients (average age: 67.1) with 30 age
      matched control subjects (average age: 65.1). Gait analysis was performed with a
      nine-camera motion-capture system and four force plates, using the Vicon Plug-In
      Gait and Vicon Nexus software. Temporal-spatial parameters were compared between
      PTTD and control subjects, and motion and ground reaction force data were
      compared between the affected limb, the contralateral limb, and the right limb in
      control subjects. RESULTS: Subjects with PTTD had increased stance phase ratio
      and decreased stride length, cadence, and gait speed. The limbs of subjects with
      PTTD showed increased knee internal rotation at lording response, which was
      biased to abduction in the knee joint during the gait cycle, and irregular hip
      flexion and knee extension moment in the terminal stance, even under control of
      gait speed. SIGNIFICANCE: We believe that the subjects with PTTD have an
      increased risk of knee osteoarthritis in both the affected and contralateral
      limbs.

PMID- 30212783
TI  - Maximum Lyapunov exponent revisited: Long-term attractor divergence of gait
      dynamics is highly sensitive to the noise structure of stride intervals.
AB  - BACKGROUND: The local dynamic stability method (maximum Lyapunov exponent) can
      assess gait stability. Two variants of the method exist: the short-term
      divergence exponent (DE), and the long-term DE. Only the short-term DE can
      predict fall risk. However, the significance of long-term DE has been unclear so
      far. Some studies have suggested that the complex, fractal-like structure of
      fluctuations among consecutive strides correlates with long-term DE. The aim,
      therefore, was to assess whether the long-term DE is a gait complexity index.
      METHODS: The study reanalyzed a dataset of trunk accelerations from 100 healthy
      adults walking at preferred speed on a treadmill for 10 min. By interpolation,
      the stride intervals were modified within the acceleration signals for the
      purpose of conserving the original shape of the signal, while imposing a known
      stride-to-stride fluctuation structure. Four types of hybrid signals with
      different noise structures were built: constant, anti-correlated, random, and
      correlated (fractal). Short- and long-term DEs were then computed. RESULTS: The
      results show that long-term DEs, but not short-term DEs, are sensitive to the
      noise structure of stride intervals. For example, it was that observed that
      random hybrid signals exhibited significantly lower long-term DEs than hybrid
      correlated signals did (0.100 vs 0.144, i.e. a 44% difference). Long-term DEs
      from constant hybrid signals were close to zero (0.006). Conversely, short-term
      DEs of anti-correlated, random, and correlated hybrid signals were closely
      grouped (2.49, 2.50, and 2.51). CONCLUSIONS: The short-term DE and the long-term
      DE, although they are both computed from divergence curves, should not be
      interpreted in a similar way. The long-term DE is very likely an index of gait
      complexity, which may be associated with gait automaticity or cautiousness.
      Consequently, to better differentiate between short- and long-term DEs, the use
      of the term attractor complexity index (ACI) is proposed for the latter.

PMID- 30212784
TI  - The performance of a multi guard ring (MGR) diode for clinical electron beams
      dosimetry.
AB  - The dosimetric response of a multi guard ring structure (MGR) diode has been
      studied with clinical electron beam energies from 5 MeV to 15 MeV. The results
      showed that the MGR dose response is linear in the range of 5-320 cGy and
      presents reproducibility with variation coefficients less than 0.4%. The field
      output factors measured with the MGR agreed within 2% with those measured with an
      ionization chamber. This study evidences that this diode can be used for clinical
      electron beam dosimetry.

PMID- 30212785
TI  - IFNG +874 A/T is associated with acute lymphoblastic leukemia in Mexican
      Mestizos.
AB  - Acute lymphoblastic leukemia (ALL), the most common type of cancer in children
      worldwide, has one of the highest incidence rates in Mexico. It is a
      multifactorial disease and different cytokine single nucleotide polymorphisms
      (SNP), have been associated with ALL expression. Few studies have been published
      analyzing IFNG +874 T/A and IL2 -330 G/T in this type of leukemia. These SNPs are
      involved in high or low expression, and are central to cellular immunity,
      influencing greatly tumor growth. The purpose of this work was to explore the
      association of IFNG +874 A/T (rs2430561) and IL2 -330 G/T (rs2069762) SNPs with
      ALL susceptibility and/or protection in 488 Mexican Mestizos patients, as
      compared to 950 Mexican Mestizo healthy controls. The results demonstrated that
      IFNG +874 T allele (pc = 0.00004, OR = 0.673) and the TT genotype (pc = 0.00015,
      OR = 0.349), protect against ALL expression with no specific gender association;
      however, the TT homozygote genotype (vs. TA+AA) seems more protective in males
      (pc = 0.00683). IL2 -330 G/T does not contribute to the development of ALL. In
      healthy Mexicans, the most common genotypes for IL2 and IFNG, are the low
      cytokine producers, suggesting that the genetic background in this ethnic group,
      may be partly responsible for the high incidence of ALL. These results show for
      the first time in Mexicans, the relevant role that IFNG SNP has in the genetic
      etiology of ALL. Thus, a large group of patients belonging to different
      ethnicities will be very helpful to study in order to demonstrate if these SNPs
      contribute to the genetic etiology of ALL, as shown here in Mexican Mestizos.

PMID- 30212786
TI  - An fMRI study of theory of mind in individuals with first episode psychosis.
AB  - Theory of mind (ToM), the ability to infer one's own and others' mental states,
      is the social cognitive process shown to have the greatest impact on functional
      outcome in schizophrenia. It is not yet known if neural abnormalities underlying
      ToM present early, during the first episode of psychosis (FEP). Fourteen FEP
      participants and twenty-two healthy control participants, aged 15-25, were
      included in analyses. All participants had a 3T magnetic resonance imaging scan
      and completed a block-design picture-story attribution-of-intentions ToM fMRI
      task, and completed a battery of behavioral social cognitive measures including a
      ToM task. General linear model analyses were carried out. Post-hoc regression
      analyses were conducted to explore whether aberrant ToM-related activation in FEP
      participants was associated with symptomatology and global social and
      occupational functioning. FEP participants, when compared to healthy controls,
      had significantly less activity in the right temporoparietal junction, right
      orbitofrontal cortex and left middle prefrontal/inferior frontal cortex, when
      making social attributions. Aberrant ToM-related activation in the right
      temporoparietal junction was associated with severity of overall psychopathology,
      but not functional outcome. Specific regions of the social brain network,
      associated with ToM, are dysfunctional in young people with FEP. Future research
      should determine whether alteration of normal brain functioning in relation to
      ToM occurs before or during illness onset.

PMID- 30212787
TI  - Structural alterations in the caudate nucleus and precuneus in un-medicated
      anorexia nervosa patients.
AB  - Anorexia nervosa (AN) is a mental disorder characterized by a preoccupation with
      thinness and may be associated with brain structural alteration. The aim of the
      study was to examine the brain structural alteration in AN patients, including
      subcortical structure volume and cortical thickness. Thirty-five un-medicated AN
      patients and 20 matched healthy controls underwent structural magnetic resonance
      imaging brain scans. High resolution structural images were acquired on a SIEMENS
      3T scanner and preprocessed using FreeSurfer software. Subcortical structure
      volume and cortical thickness were compared between the two groups. We found
      larger percentage of caudate volume relative to total grey matter (GM) volume in
      the AN group. Reduced cortical thickness at the left precuneus was also observed
      in AN patients. Moreover, an interaction between group and hemisphere was found,
      suggesting that cortical thinning was more prominent in the left hemisphere in AN
      patients. These findings provide further evidence for structural brain
      abnormalities in patients with AN.

PMID- 30212788
TI  - Parental-reported neurodevelopmental issues in Loeys-Dietz syndrome.
AB  - BACKGROUND: Loeys-Dietz syndrome (LDS) is a congenital multisystem disorder
      affecting the cardiovascular and musculoskeletal system. Limited data have
      reported neurodevelopmental (ND) issues in LDS. AIMS: To determine the extent of
      ND issues in patients with LDS. METHODS: A prospective study was performed of LDS
      patients or their caregivers. The study included data collected via an online
      survey of age-specific questions. Standard statistical methods were used for
      baseline and demographic characteristics, as well as group comparisons. OUTCOMES:
      Data were obtained from 67 patients with LDS (54% female). Median age was 14.9
      years. Gene mutations included TGFBR1 (39%), TGFBR2 (40%), SMAD3 (7%), and
      unknown (14%). Motor delays (30%, 18/61) and hypotonia (63%, 37/60) occurred
      frequently. Physical (62%, 39/62), occupational (41%, 23/56), and speech
      therapies (34%, 20/58) were common. Feeding issues were common (41%, 23/56).
      TGFBR1 mutations were more frequent among those with motor delays and feeding
      issues. CONCLUSIONS: Patients with LDS and/or their caregivers report at least
      one ND problem in most cases, and many require therapies. These data suggest ND
      disorders should be considered to be part of the phenotype.

PMID- 30212789
TI  - A transmural migration of a gossypiboma in the right colon responsible for a mass
      which mimicked an abscessed colonic tumor: A case report.
AB  - INTRODUCTION: Gossypiboma or retained surgical sponge is a rare but serious
      complication of abdominal surgery. Clinical and radiological polymorphism of
      gossypiboma makes an accurate preoperative diagnosis difficult. PRESENTATION OF
      CASE: We report an unusual case of a transmural migration of a gossypiboma in the
      right colon responsible for a mass which mimicked an abscessed colonic tumor,
      three years after an open myomectomy. A 40-year-old woman was admitted in
      emergency with generalized abdominal pain associated with fever. Initially,
      physical examination revealed an acute localized peritonitis in lower right
      quadrant. A right pericolic perforated abscess was found. A right hemicolectomy
      was performed. Surgical specimen dissection revealed an intracolonic surgical
      sponge. DISCUSSION: Gossypiboma after laparotomy may present with symptoms of
      acute surgical or chronic abdominal pain. Radiographs are the most commonly used
      method to detect retained sponges. Surgery is the preferred method of treatment
      for gossypiboma. CONCLUSION: Episodes of atypical colonic obstruction and
      nonspecific abdominal pain that have occurred for several years in a patient with
      a history of multiple abdominal surgery should be suggestive of intra-colonic
      migration of a gossypiboma. The most important approach to reduce the incidence
      of gossibypomas is prevention.

PMID- 30212790
TI  - Ischemic damage and early inflammatory infiltration are different in the core and
      penumbra lesions of rat brain after transient focal cerebral ischemia.
AB  - Clinical and experimental observations emphasize that inflammation is a direct
      risk factor for stroke. We performed a detailed histological and
      immunohistochemical analysis, assisted by digital morphometry, to compare the
      representative brain lesions in the ischemic core and penumbra in a rat model.
      Focal neuronal necrosis and degeneration were significantly more intense in the
      core, whereas inflammatory infiltration, MPO, CD68, CD3, FXIII, Cox-2, iNOS2, Arg
      1 expressions were stronger in the penumbra. Our findings indicate that
      neuroinflammation affects the penumbra more than the core and suggest that
      targeted modulation of the cellular infiltrate could be exploited to save brain
      volume.

PMID- 30212791
TI  - Bacterial community and climate change implication affected the diversity and
      abundance of antibiotic resistance genes in wetlands on the Qinghai-Tibetan
      Plateau.
AB  - Antibiotic resistance genes (ARGs) have been identified as emerging pollutants in
      the environment. However, little information is available for ARGs in natural
      wetlands at high altitude. In this study, we investigated 32 wetlands across the
      Qinghai-Tibetan Plateau, with the variation of wetland types, altitude, and
      environmental factors, to assess the determinant factor of ARGs in this area.
      ARGs were detected in all the wetlands, ranged from 1.80 * 105 to 1.35 * 107
      copies per gram of soils. The ARGs in wetland soils were diverse and abundant,
      and varied from each site, but the spatial geographical distance did not
      influence the ARG profile. The mobile genetic elements in wetlands ranged from
      3.13 * 103 to 1.02 * 106 copies per gram of soil, indicating the low abundance of
      mobile genetic elements suggests a lower transfer rate of ARGs between bacteria
      in the Plateau. Bacterial community composition was the main driver in shaping
      the ARG diversity and geographic distribution. Soil moisture and temperature were
      positively correlated with ARG abundance in this region. These results not only
      provide a better understanding of the background levels of ARGs in the Qinghai
      Tibetan Plateau, but also shed light on the influence of climate change and
      increased human activities on the distribution of ARGs.

PMID- 30212792
TI  - Efficient visible-light-driven hydrogen evolution and Cr(VI) reduction over
      porous P and Mo co-doped g-C3N4 with feeble N vacancies photocatalyst.
AB  - Developing highly efficient and inexpensive photocatalysts without noble metals,
      yet remarkably enhancing hydrogen production and Cr(VI) reduction activity, is
      highly needed. Here, the effective photocatalytic H2 evolution under visible
      light from an Eosin Y (EY)-sensitized (P, Mo)-g-C3Nx system by avoiding any noble
      metal co-catalyst is reported by the first time. Meanwhile, the optimized sample
      also displays the excellent performance in photocatalytic hexavalent chromium
      (Cr(VI)) reduction. In addition, this composite exhibits delectable stability for
      photocatalytic activities, no significant decay of activity is being observed
      after 16h reaction for photocatalytic H2 evolution (8h for Cr(VI) reduction). It
      is believed that this work will open up a new route for fabricating high
      performance and inexpensive photocatalysts for hydrogen production and Cr(VI)
      reduction.

PMID- 30212793
TI  - Korean adults' beliefs about and social distance toward attention-deficit
      hyperactivity disorder, Tourette syndrome, and autism spectrum disorder.
AB  - Given the scarcity of studies examining public beliefs regarding multiple
      neurodevelopmental disorders, this study compared lay beliefs regarding the
      etiology of attention-deficit hyperactivity disorder (ADHD), Tourette syndrome
      (TS), and autism spectrum disorder (ASD), and attitudes toward individuals with
      the disorders. We recruited 673 participants aged 20-64 years via an online panel
      survey in South Korea. Participants completed questionnaires regarding perceived
      causation of each disorder. Preferred social distance from people with the
      disorders was measured using a modified version of the Bogardus Social Distance
      Scale. Four causal factors were revealed: dietary/physical, social-environmental,
      biological, and volitive/religious. ADHD causes were considered more social
      environmental relative to TS and ASD causes, while ASD causes were considered
      more dietary/physical and biological relative to ADHD and TS causes. Preferred
      social distances for ASD and TS were the highest and lowest, respectively.
      Greater social distance from individuals with ADHD and TS was associated with
      older age; having close family members, relatives, or friends with the disorder;
      and beliefs regarding biological etiology. Greater social distance from
      individuals with ASD was associated with beliefs regarding biological etiology.
      Beliefs regarding ADHD, TS, and ASD causes and attitudes toward the disorders
      differed, and beliefs regarding etiology affected preferred social distance.

PMID- 30212794
TI  - Mytilus spp. as sentinels for monitoring microplastic pollution in Norwegian
      coastal waters: A qualitative and quantitative study.
AB  - Microplastic (MP) contamination is ubiquitous in the environment and many species
      worldwide have been shown to contain MP. The ecological impact of MP pollution is
      still unknown, thus there is an urgent need for more knowledge. One key task is
      to identify species suitable as sentinels for monitoring in key eco-compartments,
      such as coastal waters. In Norway, mussels (Mytilus spp.) have been monitored for
      hazardous contaminants through OSPAR since 1981. Norway has the longest coastline
      in Europe and adding MP to the Norwegian Mussel Watch is therefore important in a
      European and global context. The present study reports MP data in mussels (332
      specimens) collected from multiple sites (n = 15) spanning the whole Norwegian
      coastline. MPs were detected at all locations, except at one site on the west
      coast. Among the most surprising findings, mussels from the Barents Sea coastline
      in the Finnmark region, contained significantly more MPs than mussels from most
      of the southern part of the country, despite the latter sites being located much
      closer to major urban areas. Only mussels from a site located very close to Oslo,
      the capital, contained levels similar to those observed in the remote site in
      Finnmark. In total an average of 1.5 (+/-2.3) particles ind-1 and 0.97 (+/-2.61)
      particles w.w. g-1 was found. The most common MPs were <1 mm in size, and fibres
      accounted for 83% of particles identified, although there was inter-site
      variability. Thirteen different polymeric groups were identified; cellulosic
      being the most common and black rubbery particles being the second. This study
      suggests Mytilus spp. are suitable for semi-quantitative and qualitatively
      monitoring of MPs in coastal waters. However, some uncertainties remain including
      mussel size as a confounding factor that may influence ingestion, the role of
      depuration and other fate related processes, and this call for further research.

PMID- 30212795
TI  - Minimizing the effect of precipitation in clarifying the responses of leaf N and
      P stoichiometry to temperature.
AB  - How terrestrial ecosystem responds to global warming has received wide attention.
      Plant stoichiometry has the potential to reflect ecosystem responses to climate
      change, thus, investigating the variations in plant stoichiometry with
      temperature is important and necessary for revealing the responses of terrestrial
      ecosystem to global warming. Although many studies had explored the relationships
      between plant N, P stoichiometry and temperature, previous field investigations
      did not eliminate the interference of precipitation effect with these observed
      relationships. To minimize the effect of precipitation on leaf N, P
      stoichiometry, this investigation was conducted across a temperature gradient
      over broad geographical scale along the 400 mm isohyet, which extends about 6000
      km in China. This study showed that leaf N did not vary, whereas leaf P decreased
      and leaf N:P ratio increased with increasing mean annual temperature (MAT). The
      responses of leaf N and P stoichiometry to MAT observed in this study might be
      general patterns; because they were almost ubiquitous across functional groups,
      genera and species examined, and moreover, they were independent of vegetation
      and soil type. It could be inferred from this study that global warming in future
      will have no effect on leaf N, but reduce leaf P and increase leaf N:P ratio.
      Stable leaf N and varied leaf P with changing MAT suggested that leaf N and P
      decoupled with changing temperature.

PMID- 30212796
TI  - Using an innovative flag element ratio approach to tracking potential sources of
      heavy metals on urban road surfaces.
AB  - Heavy metals deposited on urban road surfaces can be washed-off by stormwater
      runoff, undermining stormwater reuse safety due to their high toxicity to
      ecological and human health. Heavy metals on urban road surfaces come from
      diverse sources and tracking these sources is essential to effectively manage
      stormwater and hence its reuse safety. This research study developed an
      innovative approach to tracking sources of heavy metals using data collected in
      Shenzhen, China. This approach developed was based on a "flag element ratio"
      theory, where each source generally corresponds to a specific ratio of targeted
      pollutants to the flag element. It is noted that Cr, Cu, Pb, Ni, and Zn on urban
      roads were 19.05 mg/kg to 152.01 mg/kg, 25.66 mg/kg to 310.75 mg/kg, 15.61 mg/kg
      to 220.35 mg/kg, 10.65 mg/kg to 100.28 mg/kg, and 138.14 mg/kg to 1047.05 mg/kg,
      respectively. Gasoline emission was the main source for Cr, Ni and Pb, while
      braking wear and tyre wear were the major sources of Cu and Zn, respectively.
      Furthermore, the rankings of sources of each heavy metal in terms of their
      contributions were obtained by using this approach. Vehicle exhaust was found as
      the main contributor for all the heavy metals on urban road surfaces. This
      highlighted that vehicle exhaust should be seriously considered in terms of
      controlling heavy metal pollution on urban road surfaces and hence resulting
      urban road stormwater runoff.

PMID- 30212797
TI  - Joining empirical and modelling approaches to estimate dry deposition of nitrogen
      in Mediterranean forests.
AB  - In Mediterranean areas, dry deposition is a major component of the total
      atmospheric N input to natural habitats, particularly to forest ecosystems. An
      innovative approach, combining the empirical inferential method (EIM) for surface
      deposition of NO3- and NH4+ with stomatal uptake of NH3, HNO3 and NO2 derived
      from the DO3SE (Deposition of Ozone and Stomatal Exchange) model, was used to
      estimate total dry deposition of inorganic N air pollutants in four holm oak
      forests under Mediterranean conditions in Spain. The estimated total deposition
      varied among the sites and matched the geographical patterns previously found in
      model estimates: higher deposition was determined at the northern site (28.9 kg N
      ha-1 year-1) and at the northeastern sites (17.8 and 12.5 kg N ha-1 year-1) than
      at the central-Spain site (9.4 kg N ha-1 year-1). On average, the estimated dry
      deposition of atmospheric N represented 77% +/- 2% of the total deposition of N,
      of which surface deposition of gaseous and particulate atmospheric N averaged
      10.0 +/- 2.9 kg N ha-1 year-1 for the four sites (58% of the total deposition),
      and stomatal deposition of N gases averaged 3.3 +/- 0.8 kg N ha-1 year-1 (19% of
      the total deposition). Deposition of atmospheric inorganic N was dominated by the
      surface deposition of oxidized N in all the forests (means of 54% and 42% of the
      dry and total deposition, respectively). The relative contribution of NO2 to dry
      deposition averaged from 19% in the peri-urban forests to 11% in the most natural
      site. During the monitoring period, the empirical critical loads provisionally
      proposed for ecosystem protection (10-20 kg N ha-1 year-1) was exceeded in three
      of the four studied forests.

PMID- 30212798
TI  - Degradation of various insecticides in cooked eggs during in vitro human
      digestion.
AB  - The objective of this study was to determine the effects of cooking and in vitro
      human digestion on the changes of five insecticides-fipronil, bifenthrin, 1,1,1
      trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethane (DDD), and 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE)
      in egg whites and yolks. Each insecticide was applied to egg whites and yolks at
      a concentration of 1000 MUg/g. After cooking the egg whites and yolks,
      concentrations of bifenthrin, DDD, and DDE decreased (P < 0.05), whereas those of
      fipronil and DDT were unchanged (P > 0.05) in both egg whites and yolks. Next, an
      in vitro human digestion model that simulates all the steps of human digestion
      was employed. Until digestion in the small intestine, the concentrations of
      fipronil and DDT in the cooked egg whites and yolks were unchanged (P > 0.05),
      whereas those of bifenthrin, DDD, and DDE decreased (P < 0.05) at each digestion
      step. In the large intestinal digestion step with Escherichia coli and
      Lactobacillus sakei as enterobacteria, the concentrations of all the insecticides
      decreased (P < 0.05) in the cooked egg whites and yolks. Among the insecticides,
      bifenthrin showed the lowest concentration (P < 0.05). In conclusion, the use of
      bifenthrin as an insecticide would be comparatively less toxic than other
      insecticides in terms of environmental pollution and human health, because of its
      easy degradation.

PMID- 30212799
TI  - Occurrence and partitioning behavior of perfluoroalkyl acids in wastewater
      effluent discharging into the Long Island Sound.
AB  - Perfluoroalkyl acids (PFAAs) were measured in aqueous and suspended particulate
      matter (SPM) fractions in the final effluents from 12 wastewater treatment
      facilities located around the Connecticut shoreline. Aqueous phase concentrations
      ranged from 53 to 198 ng/L for ?PFAAs with <=7 perfluorinated carbons (CF2) and 2
      73 ng/L for >7 CF2 PFAAs. Predominant PFAAs associated with effluent derived SPM
      were perfluorodecanoic acid and perflurorooctane sulfonic acid, detected in 48%
      and 52% of samples in concentrations ranging from <LOQ-1770 ng/g and <LOQ-2750
      ng/g respectively. Based on the range of concentrations detected and the average
      flow of final effluent to the Long Island Sound (LIS), average total annual PFAA
      mass loads from wastewater treatment facilities to the LIS is estimated in the
      range of 70-315 kg/year, with 4-100 kg/year consisting of >7 CF2 PFAAs.
      Partitioning coefficients (log KOC) derived for effluent water and SPM phases
      (4.2 +/- 0.3, 4.4 +/- 0.4, 5.1 +/- 0.2 and 5.3 +/- 0.2 for PFOA, PFNA PFDA and
      PFUnA; 4.5 +/- 0.2 and 5.2 +/- 0.2 for PFOS and PFHsX respectively) were found to
      be of similar magnitude to aeration tank particles, though 0.5 to 2 log units
      greater than sludge solids and to natural system particulates including riverine
      SPM, estuarine SPM and sediments. Results from this study suggest that effluent
      derived suspended particulate matter could be an effective vector in the
      transport of long-chained PFAAs through wastewater treatment into receiving
      waters, and a potential vector to the local food chain.

PMID- 30212800
TI  - Utility of virtual monoenergetic images derived from a dual-layer detector-based
      spectral CT in the assessment of aortic anatomy and pathology: A retrospective
      case control study.
AB  - OBJECTIVES: To evaluate the ability of the retrospectively generated virtual
      monoenergetic images (VMIs) from a dual-layer detector-based spectral computed
      tomography (SDCT) to augment aortic enhancement for the evaluation of aortic
      anatomy and pathology. METHODS: 98 patients with suboptimal aortic enhancement
      (<=200 HU) were retrospectively identified from SDCT scans. VMI from 40 to 80 keV
      were generated. Attenuation, noise, SNR, and CNR were measured at seven levels in
      the aorta. Image quality was graded on a 5-point scale, 5 being the best. From
      the VMI, an ideal set was chosen with mean vascular attenuation above 200 HU
      while maintaining diagnostic quality. Image parameters and quality of this ideal
      set were compared to the standard 120-kVp images. RESULTS: The mean attenuation
      of all seven measured anatomical regions was 156.6 +/- 61.7 HU in the 120-kVp
      images. Attenuation of the VMI from 40 to 70 keV were higher than the 120-kVp
      image, measuring 439.2 +/- 215.3 HU, 298.5 +/- 140.6 HU, 213.4 +/- 94.3 HU, and
      164.7 +/- 90.2 HU, for 40 keV, 50 keV, 60 keV, and 70 keV, respectively (p value
      <0.01 for 40, 50, 60 keV; 0.07 for 70 keV). SNR and CNR showed similar trends.
      The 50 keV VMI had the best image quality (4.48 +/- 0.84 vs. 2.24 +/- 0.92 on 120
      kVp images, p < 0.001). Attenuation, CNR, and SNR increased by 90.6%, 85.0%, and
      108.1% at 50 keV compared to 120-kVp. CONCLUSIONS: A contrast-enhanced CT study
      can be optimized for the assessment of the aorta by using low-energy VMI obtained
      using SDCT. At the optimal monoenergetic level, attenuation, SNR, CNR and image
      quality were significantly higher than that of conventional polyenergetic images.

PMID- 30212801
TI  - 25-Hydroxycholesterol and 27-hydroxycholesterol inhibit human rotavirus infection
      by sequestering viral particles into late endosomes.
AB  - A novel innate immune strategy, involving specific cholesterol oxidation products
      as effectors, has begun to reveal connections between cholesterol metabolism and
      immune response against viral infections. Indeed, 25-hydroxycholesterol (25HC)
      and 27-hydroxycholesterol (27HC), physiologically produced by enzymatic oxidation
      of cholesterol, act as inhibitors of a wide spectrum of enveloped and non
      enveloped human viruses. However, the mechanisms underlying their protective
      effects against non-enveloped viruses are almost completely unexplored. To get
      insight into this field, we investigated the antiviral activity of 25HC and 27HC
      against a non-enveloped virus causing acute gastroenteritis in children, the
      human rotavirus (HRV). We found that 25HC and 27HC block the infectivity of
      several HRV strains at 50% inhibitory concentrations in the low micromolar range
      in the absence of cell toxicity. Both molecules affect the final step of virus
      penetration into cells by preventing the association of two cellular proteins:
      the oxysterol binding protein (OSBP) and the vesicle-associated membrane protein
      associated protein-A (VAP-A). By altering the activity of these cellular
      mediators, 25HC and 27HC disturb the recycling of cholesterol between the
      endoplasmic reticulum and the late endosomes which are exploited by HRV to
      penetrate into the cell. The substantial accumulation of cholesterol in the late
      endosomal compartment results in sequestering viral particles inside these
      vesicles thereby preventing cytoplasmic virus replication. These findings suggest
      that cholesterol oxidation products of enzymatic origin might be primary
      effectors of host restriction strategies to counteract HRV infection and point to
      redox active lipids involvement in viral infections as a research area of focus
      to better focus in order to identify novel antiviral agents targets.

PMID- 30212802
TI  - Selenium supplementation of lung epithelial cells enhances nuclear factor E2
      related factor 2 (Nrf2) activation following thioredoxin reductase inhibition.
AB  - The trace element selenium (Se) contributes to redox signaling, antioxidant
      defense, and immune responses in critically ill neonatal and adult patients. Se
      is required for the synthesis and function of selenoenzymes including thioredoxin
      (Trx) reductase-1 (TXNRD1) and glutathione peroxidases (GPx). We have previously
      identified TXNRD1, primarily expressed by airway epithelia, as a promising
      therapeutic target to prevent lung injury, likely via nuclear factor E2-related
      factor 2 (Nrf2)-dependent mechanisms. The present studies utilized the TXNRD1
      inhibitor auranofin (AFN) to test the hypothesis that Se positively influences
      Nrf2 activation and selenoenzyme responses in lung epithelial cells. Murine
      transformed Club cells (mtCCs) were supplemented with 0, 10, 25, or 100 nM
      Na2SeO3 to create a range of Se conditions and were cultured in the presence or
      absence of 0.5 MUM AFN. TXNRD1 and GPX2 protein expression and enzymatic activity
      were significantly greater upon Se supplementation (p < 0.05). AFN treatment (0.5
      MUM AFN for 1 h) significantly inhibited TXNRD1 but not GPx activity (p < 0.001).
      Recovery of TXNRD1 activity following AFN treatment was significantly enhanced by
      Se supplementation (p < 0.041). Finally, AFN-induced Nrf2 transcriptional
      activation was significantly greater in mtCCs supplemented in 25 or 100 nM
      Na2SeO3 when compared to non-supplemented controls (p < 0.05). Our novel studies
      indicate that Se levels positively influence Nrf2 activation and selenoenzyme
      responses following TXNRD1 inhibition. These data suggest that Se status
      significantly influences physiologic responses to TXNRD1 inhibitors. In
      conclusion, correction of clinical Se deficiency, if present, will be necessary
      for optimal therapeutic effectiveness of TXNRD1 inhibitors in the prevention of
      lung disease.

PMID- 30212803
TI  - Bisphenol S instead of Bisphenol A: Toxicokinetic investigations in the ovine
      materno-feto-placental unit.
AB  - Bisphenol S (BPS) is widely used as a substitute for Bisphenol A in consumer
      products. Despite its potential endocrine-disrupting effects and widespread
      exposure, toxicokinetic data, particularly during the critical period of
      pregnancy, are not available for BPS. The objectives of our study were to
      evaluate the mechanisms determining fetal exposure to BPS and to BPS glucuronide
      (BPSG) and to compare them with those prevailing for BPA. The disposition of BPS
      and BPSG was evaluated in the materno-fetal unit of the catheterized pregnant ewe
      model, following intravenous administrations of BPS and BPSG to mothers and their
      fetuses. In a second experiment, the rate of BPS accumulation in the fetal
      compartment was determined under steady-state conditions after repeated
      intravenous BPS administrations to the mother. In the maternal compartment, BPS
      was mainly metabolized into BPSG and totally eliminated in urine. Only 0.40% of
      the maternal dose was transferred to the fetus. However, once in the fetal
      compartment, 26% of the fetal dose was rapidly eliminated through placental
      transfer, while 46% of BPS was metabolized into BPSG which remained trapped in
      the fetal compartment. Thus, the elimination of BPSG from the fetal compartment
      required its back-conversion into bioactive BPS, leading to an 87% enhancement of
      the fetal BPS exposure. Our findings demonstrate that, despite the low materno
      fetal placental transfer of BPS, this substitute for BPA is able to accumulate in
      the fetal compartment after repeated maternal exposure, leading to chronic fetal
      exposure to BPS in a range of concentrations similar to those of BPA.

PMID- 30212805
TI  - Effect of epileptiform abnormality burden on neurologic outcome and antiepileptic
      drug management after subarachnoid hemorrhage.
AB  - OBJECTIVE: To quantify the burden of epileptiform abnormalities (EAs) including
      seizures, periodic and rhythmic activity, and sporadic discharges in patients
      with aneurysmal subarachnoid hemorrhage (aSAH), and assess the effect of EA
      burden and treatment on outcomes. METHODS: Retrospective analysis of 136 high
      grade aSAH patients. EAs were defined using the American Clinical Neurophysiology
      Society nomenclature. Burden was defined as prevalence of <1%, 1-9%, 10-49%, 50
      89%, and >90% for each 18-24 hour epoch. Our outcome measure was 3-month Glasgow
      Outcome Score. RESULTS: 47.8% patients had EAs. After adjusting for clinical
      covariates EA burden on first day of recording and maximum daily burden were
      associated with worse outcomes. Patients with higher EA burden were more likely
      to be treated with anti-epileptic drugs (AEDs) beyond the standard prophylactic
      protocol. There was no difference in outcomes between patients continued on AEDs
      beyond standard prophylaxis compared to those who were not. CONCLUSIONS: Higher
      burden of EAs in aSAH independently predicts worse outcome. Although nearly half
      of these patients received treatment, our data suggest current AED management
      practices may not influence outcome. SIGNIFICANCE: EA burden predicts worse
      outcomes and may serve as a target for prospective interventional controlled
      studies to directly assess the impact of AEDs, and create evidence-based
      treatment protocols.

PMID- 30212806
TI  - Application of untargeted metabolomics for the detection of pathogenic Naegleria
      fowleri in an operational drinking water distribution system.
AB  - Found in drinking water distribution systems (DWDSs), swimming pools, and
      recreational waters, N. fowleri, is the causative agent of primary amoebic
      meningoencephalitis (PAM). Although cases of N. fowleri infections are rare, the
      fatality is comparatively high (>95%) and surveillance is essential to minimize
      N. fowleri infections. However, conventional N. fowleri detection methods are
      less satisfying owing to their time-consuming and lab intensive characteristics
      as well as the lack of the ability to determine viability. As a result, an
      alternative detection approach capable of determining viability as well as
      species identification is required to better ensure public health. Based on our
      previous research focusing on distinguishing laboratory cultured N. fowleri from
      N. lovaniensis and N. italica, this study applies untargeted metabolomics methods
      to field samples from operational DWDSs. A list of diagnostic features was found
      to preliminarily discriminate the N. fowleri positive from N. fowleri negative
      and N. lovaniensis positive field samples with satisfying predictive accuracy.
      The results outlined in this manuscript further validate and improve the
      metabolite-based N. fowleri detection approach, potentially aiding water
      utilities in the detection and management of N. fowleri in drinking water.

PMID- 30212804
TI  - Multidisciplinary development of the Geriatric Core Dataset for clinical research
      in older patients with cancer: A French initiative with international survey.
AB  - BACKGROUND: To define a core set of geriatric data to be methodically collected
      in clinical cancer trials of older adults, enabling comparison across trials.
      PATIENTS AND METHODS: Following a consensus approach, a panel of 14 geriatricians
      from oncology clinics identified seven domains of importance in geriatric
      assessment. Based on the international recommendations, geriatricians selected
      the mostly commonly used tools/items for geriatric assessment by domain (January
      October 2015). The Geriatric Core Dataset (G-CODE) was progressively developed
      according to RAND appropriateness ratings and feedback during three successive
      Delphi rounds (July-September 2016). The face validity of the G-CODE was assessed
      with two large panels of health professionals (55 national and 42 international
      experts) involved both in clinical practice and cancer trials (March-September
      2017). RESULTS AND DISCUSSION: After the last Delphi round, the tools/items
      proposed for the G-CODE were the following: (1) social assessment: living alone
      or support requested to stay at home; (2) functional autonomy: Activities of
      Daily Living (ADL) questionnaire and short instrumental ADL questionnaire; (3)
      mobility: Timed Up and Go test; (4) nutrition: weight loss during the past 6
      months and body mass index; (5) cognition: Mini-Cog test; (6) mood: mini
      Geriatric Depression Scale and (7) comorbidity: updated Charlson Comorbidity
      Index. More than 70% of national experts (42 from 20 cities) and international
      experts (31 from 13 countries) participated. National and international surveys
      showed good acceptability of the G-CODE. Specific points discussed included age
      year cut-off, threshold of each tool/item and information about social support,
      but no additional item was proposed. CONCLUSION: We achieved formal consensus on
      a set of geriatric data to be collected in cancer trials of older patients. The
      dissemination and prospective use of the G-CODE is needed to assess its utility.

PMID- 30212807
TI  - Further developing the bacterial growth potential method for ultra-pure drinking
      water produced by remineralization of reverse osmosis permeate.
AB  - Ensuring the biological stability of drinking water is essential for modern
      drinking water supply. To understand and manage the biological stability, it is
      critical that the bacterial growth in drinking water can be measured. Nowadays,
      advance treatment technologies, such as reverse osmosis (RO), are increasingly
      applied in drinking water purification where the produced water is characterized
      by low levels of nutrients and cell counts. The challenge is, therefore, how to
      measure the low bacterial growth potential (BGP) of such ultra-pure water using
      the available methods which were originally developed for conventionally treated
      drinking water. In this study, we proposed a protocol to assess BGP of ultra-pure
      drinking water produced by RO and post-treatment (including remineralization).
      Natural bacterial consortium from conventional drinking water was added to all
      water samples during this study to ensure the presence of a wide range of
      bacterial strains. The method development included developing an ultra-pure blank
      with high reproducibility to lower the detection limit of the BGP method (50 +/-
      20 * 103 intact cells/mL) compared with conventional blanks such as bottled
      spring water, deep groundwater treated by aeration and slow sand filtrate of
      surface water supply. The ultra-low blank consists of RO permeate after adjusting
      its pH and essential mineral content under controlled laboratory conditions to
      ensure carbon limitation. Regarding the test protocol, inoculum concentrations of
      >10 * 103 intact cells/mL may have a significant contribution to the measured low
      levels of BGP. Pasteurization of water samples before measuring BGP is necessary
      to ensure reliable bacterial growth curves. The optimized method was used to
      assess BGP of ultra-pure drinking water produced by RO membranes and post
      treatment (including remineralization), where the BGP has decreased more than 6
      fold to a level of 90 +/- 20 * 103 intact cells/mL compared with conventionally
      treated water (630 +/- 70 * 103 intact cells/mL).

PMID- 30212808
TI  - Formation of abstract task representations: Exploring dosage and mechanisms of
      working memory training effects.
AB  - Working memory is strongly involved in human reasoning, abstract thinking and
      decision making. Past studies have shown that working memory training generalizes
      to untrained working memory tasks with similar structure (near-transfer effect).
      Here, we focused on two questions: First, we ask how much training might be
      required in order to find a reliable near-transfer effect? Second, we ask which
      choice- mechanism might underlie training benefits? Participants were allocated
      to one of three groups: working-memory training (combined set-shifting and N-back
      task), active-control (visual search) and no-contact control. During pre/post
      testing, all participants completed tests tapping procedural and declarative
      working memory as well as reasoning. We found improved performance only in the
      procedural working-memory transfer tasks, a transfer task that shared a similar
      structure to that of the training task. Intermediate testing throughout the
      training period suggest that this effect emerged as soon as after 2 training
      sessions. We applied evidence accumulation modeling to investigate the choice
      process responsible for this near-transfer effect and found that trained
      participants, compared with active-controls had quicker retrieval of the action
      rules, and more efficient classification of the target. We conclude that
      participants were able to form abstract representations of the task procedure
      (i.e., stimulus-response rules) that was then ~applied to novel stimuli and
      responses.

PMID- 30212809
TI  - Feasibility of Underwater Clip Closure for Large Mucosal Defects after Colorectal
      Endoscopic Submucosal Dissection.
AB  - BACKGROUND/AIMS: Clip closure of mucosal defects after colorectal endoscopic
      submucosal dissection (C-ESD) may decrease the incidence of delayed adverse
      events. The size of the defect to be closed by conventional clip is limited,
      however, and we sometimes encounter incomplete closure when the defect is located
      at the flexure. As, theoretically, underwater clip closure (UCC) could achieve
      complete closure despite these difficult cases, we investigated its feasibility.
      METHODS: We retrospectively analyzed 21 patients who underwent UCC after C-ESD.
      The main outcome was the UCC success rate, defined as complete closure of the
      defect. Other outcomes were procedure time, number of clips, and the delayed
      adverse event rate. RESULTS: The median resected specimen size was 31 mm (range
      18-47 mm). The UCC success rate was 100%. The median procedure time was only 11
      min (range 6-21 min). The median number of clips was 9 (range 5-16). No delayed
      adverse event occurred. CONCLUSION: It is feasible to use UCC to close large
      mucosal defects, although further studies are warranted to assess its efficacy.

PMID- 30212810
TI  - Environmental Influences on Neuromorphology in the Non-Native Starling Sturnus
      vulgaris.
AB  - Cognitive traits are predicted to be under intense selection in animals moving
      into new environments and may determine the success, or otherwise, of dispersal
      and invasions. In particular, spatial information related to resource
      distribution is an important determinant of neural development. Spatial
      information is predicted to vary for invasive species encountering novel
      environments. However, few studies have tested how cognition or neural
      development varies intraspecifically within an invasive species. In Australia,
      the non-native common starling Sturnus vulgaris inhabits a range of habitats that
      vary in seasonal resource availability and distribution. We aimed to identify
      variations in the brain mass and hippocampus volume of starlings in Australia
      related to environmental variation across two substantially different habitat
      types. Specifically, we predicted variation in brain mass and hippocampal volume
      in relation to environmental conditions, latitude, and climatic variables. To
      test this, brain mass and volumes of the hippocampus and two control brain
      regions (telencephalon and tractus septomesencephalicus) were quantified from
      starling brains gathered from across the species' range in south eastern
      Australia. When comparing across an environmental gradient, there was a
      significant interaction between sex and environment for overall brain mass, with
      greater sexual dimorphism in brain mass in inland populations compared to those
      at the coast. There was no significant difference in hippocampal volume in
      relation to environmental measures (hippocampus volume, n = 17) for either sex.
      While these data provide no evidence for intraspecific environmental drivers for
      changes in hippocampus volume in European starlings in Australia, they do suggest
      that environmental factors contribute to sex differences in brain mass. This
      study identifies associations between the brain volume of a non-native species
      and the environment; further work in this area is required to elucidate the
      mechanisms driving this relationship.

PMID- 30212811
TI  - Comparison of Clinical Characteristics of Patients with Acute Esophageal Mucosal
      Lesion and those with Severe Reflux Esophagitis.
AB  - BACKGROUND: The term "acute esophageal mucosal lesion (AEML)" includes black
      esophagitis, and non-black esophagitis characterized by diffuse circumferential
      erosions without black-appearing mucosa. Black esophagitis is easily diagnosed,
      whereas non-black esophagitis is often misdiagnosed as severe reflux esophagitis
      (sRE). The aim of this study was to determine differences in clinical
      characteristics of patients with AEML and those with sRE. METHODS: Thirty-nine
      patients with sRE and 32 patients with AEML were diagnosed on the basis of
      endoscopic findings from 2009 to 2016. Characteristics assessed included age,
      sex, medication use, coexisting endoscopic finding, comorbidities, laboratory
      tests results, and chief complaints. RESULTS: In contrast with sRE, male sex,
      need for emergency endoscopy, presence of duodenal lesions, hypertension, and
      renal dysfunction were positively associated with AEML. Analysis of associations
      between laboratory data and AEML showed that high white blood cell count, blood
      urea nitrogen, and blood glucose were significantly associated with an increase
      OR for AEML. CONCLUSIONS: We showed that AEML differed from sRE regarding both
      endoscopic findings and clinicopathological features. AEML has not been widely
      recognized, but it should be defined as a distinct inflammatory disease of the
      esophagus consisting of both black and non-black esophagitis.

PMID- 30212813
TI  - Evidence of Cross-Reactivity between Different Seed Storage Proteins from
      Hazelnut (Corylus avellana) and Walnut (Juglans regia) Using Recombinant Allergen
      Proteins.
AB  - Seed storage proteins are extremely stable allergens in nuts, seeds, and legumes
      and are responsible for the most severe allergic reactions to these foods. The
      cross-reactivity between seed storage proteins from different sources has not
      been studied at a molecular level so far. This study aimed to ascertain the cross
      reactivity between walnut and hazelnut seed storage proteins using recombinant
      allergens. Sera from 13 consecutive patients with severe primary walnut and/or
      hazelnut allergy and hypersensitive to both nuts were studied. IgE specific for
      rCor a 9, rCor a 14, and rJug r 1 was measured, and inhibition experiments were
      carried out by measuring IgE reactivity after absorption of patients' sera with
      freshly prepared walnut extract. All 13 sera showed strong IgE reactivity against
      walnut 2S albumin, Jug r 1, 12 reacted to hazelnut 2S albumin, Cor a 14, and 8 to
      the hazelnut legumin, Cor a 9. In inhibition experiments, absorption of sera with
      whole walnut extract led to the complete disappearance of IgE reactivity to Jug r
      1 in 12/13 cases, as expected, but also to the complete disappearance of specific
      IgE to Cor a 14 in 9/12 sera, and of IgE reactivity to Cor a 9 in 7/8. In the
      remaining cases a dramatic drop in IgE reactivity was observed. The study shows
      that patients primarily allergic to either walnut or hazelnut showing a skin or
      serological reactivity to the other nut also are potentially at risk of severe
      allergic reactions caused by cross-reactivity between 2S albumins and legumins.

PMID- 30212812
TI  - Rac Regulates the TRAP-Induced Release of Phosphorylated-HSP27 from Human
      Platelets via p38 MAP Kinase but Not JNK.
AB  - BACKGROUND/AIMS: Thrombin induces the activation of human platelets through
      protease-activated receptor (PAR) 1 and PAR4, and Rac, a member of the Rho family
      of small GTPases, is implicated in PAR activation. We previously reported that
      phosphorylated-heat shock protein 27 (HSP27) is released from the thrombin
      receptor-activating peptide (TRAP)-stimulated platelets of diabetic patients. In
      the present study, we investigated the role of Rac in the TRAP-elicited release
      of phosphorylated-HSP27 from human platelets. METHODS: Platelet aggregation was
      measured using an aggregometer with laser scattering. Protein phosphorylation was
      analyzed by Western blotting. The levels of phosphorylated-HSP27 and platelet
      derived growth factor-AB (PDGF-AB) were measured by enzyme-linked immunosorbent
      assays. RESULTS: NSC23766, an inhibitor of Rac-guanine nucleotide exchange factor
      interaction, suppressed the TRAP-elicited release of phosphorylated-HSP27 as well
      as platelet aggregation. The TRAP-induced phosphorylation of HSP27, p38 mitogen
      activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) was attenuated
      by NSC23766. SB203580, a p38 MAPK inhibitor, but not SP600125, a JNK inhibitor,
      suppressed the release of phosphorylated-HSP27 in addition to HSP27
      phosphorylation. On the other hand, both SB203580 and SP600125 reduced the TRAP
      stimulated secretion of PDGF-AB. CONCLUSION: Our results strongly suggest that
      Rac acts as a positive regulator of the PAR-elicited release of phosphorylated
      HSP27 from human platelets via p38 MAPK but not JNK.

PMID- 30212814
TI  - Clear Liquids versus Polyethylene Glycol Preparation for Video Capsule Endoscopy
      of the Small Bowel: A Randomized Controlled Trial.
AB  - BACKGROUND: An effective bowel cleanse can improve the imaging quality of video
      capsule endoscopy (VCE). We aimed to further investigate the optimal small bowel
      cleanse method by comparing the efficacy of 4 L of clear liquids, 2 L of
      polyethylene glycol (PEG), and 4 L of PEG on the image quality of VCE. METHODS: A
      randomized controlled, non-inferiority trial was performed comparing 4 L of clear
      liquids (Group A), 2 L of PEG (Group B), and 4 L of PEG (Group C). The primary
      endpoint was image quality between the groups. The secondary endpoints included
      patient tolerability and side effects. RESULTS: Eighty-one patients were analyzed
      in group A, 84 patients were analyzed in group B, and 80 patients were analyzed
      in group C. Image quality scores revealed 4 L of clear liquids to be non-inferior
      to 2 L of PEG, and 2 L of PEG to be non-inferior to 4 L of PEG (p < 0.0167).
      Group A had a lower difficulty of completion rate than Group B and Group C and a
      lower rate of side effects when compared to Group C (p < 0.0167). CONCLUSION:
      Four liters of clear liquids should be considered a routine method for small
      bowel preparation prior to VCE.

PMID- 30212815
TI  - Plasma Drug Concentrations in Children Receiving Pulmonary Arterial Hypertension
      Combination Treatment.

PMID- 30212816
TI  - Correlations between the Recurrence Patterns and Sizes of Lateral Pelvic Lymph
      Nodes before and after Chemoradiotherapy in Patients with Lower Rectal Cancer.
AB  - OBJECTIVE: Factors that predict rectal cancer metastasis to the lungs remain
      undefined. We investigated whether the lateral pelvic lymph node (LPN) sizes
      before and after chemoradiotherapy (CRT) correlate with lung metastasis after
      surgery for lower rectal cancer. METHODS: Two hundred and forty patients with
      lower rectal cancer who received preoperative CRT and curative surgery between
      2003 and 2017 were examined. Computed tomography-measured LPN sizes before and
      after CRT were retrospectively determined by 1 colorectal surgeon who was blinded
      to the patients' clinical and pathological outcomes. RESULTS: The 5-year
      cumulative lung metastasis rates were 15.2%. The mean LPN sizes in patients who
      developed lung metastasis were larger than those in patients who did not (pre
      CRT: 8.7 vs. 6.3 mm, p = 0.003; post-CRT: 6.8 vs. 4.5 mm, p = 0.001). The
      cumulative lung metastasis rate in patients with large LPNs was higher than in
      those with small LPNs both before and after CRT. On multivariate analysis, lung
      metastasis was independently correlated with the LPN size only after CRT (hazard
      ratio [HR]: 5.58), together with the ypT stage (HR: 2.96) and the tumor location
      (HR: 0.38). CONCLUSIONS: LPN size after CRT is strongly predictive of
      postoperative lung metastasis in patients with lower rectal cancer.

PMID- 30212817
TI  - Treatment of Oesophageal Varices in Liver Cirrhosis.
AB  - BACKGROUND: The development of cirrhosis with resultant portal hypertension can
      lead to oesophageal varices at a rate of 7% per annum. Bleeding from varices
      happens when the portal pressure is >=12 mm Hg and can threaten life. SUMMARY:
      Eliminating the aetiology of cirrhosis is a pivotal step to prevent the formation
      of varices. In patients with established varices, primary prophylaxis with non
      selective beta blockers (NSBB) may slow down the progression of varices and
      prevent the first variceal bleed. NSBB, similar to other agents such as
      renin/angiotensin blockers, statins, and rifaximin, may have the additional
      advantage of blunting inflammatory stimuli, which can contribute to the
      progression of varices. Variceal band ligation is an alternative for primary
      bleeding prophylaxis with excellent results. Any acute variceal bleed should be
      managed with band ligation after careful resuscitation. Early pre-emptive
      transjugular intrahepatic portosystemic shunt (TIPS) in decompensated cirrhotic
      patients is very effective in controlling the bleeding and improves survival.
      Secondary prophylaxis against further variceal bleeding using NSBB and band
      ligation is recommended in most other patients. TIPS may be considered in
      appropriate patients as a secondary prophylaxis against recurrent variceal bleed.
      Future research should be directed towards the prevention of varices and
      targeting inflammation to reduce cirrhotic complications. Key Messages: Treatment
      strategies depend on the stage the patient is at along the natural history of
      varices: NSBB or band ligation for primary prophylaxis; band ligation or early
      TIPS for acute bleed; and a combination of NSBB + band ligation or TIPS for
      secondary prophylaxis (Fig. <xref ref-type="fig" rid="f01">1</xref>).

PMID- 30212818
TI  - Diagnosing Alport Syndrome: Lessons from the Pediatric Ward.
AB  - BACKGROUND: Alport syndrome is a rare inheritable kidney disease frequently
      leading to end-stage kidney disease in young adults. Patients could benefit from
      early recognition of the disease. In several children with Alport syndrome, a
      parent was noticed to have renal symptoms attributed to another renal disease.
      AIM: To review the renal history of the closest family members of a cohort of
      pediatric patients with genetically proven Alport syndrome. METHODS: The medical
      records of all children with genetically proven Alport syndrome identified at our
      pediatric nephrology department in the last 20 years were reviewed, with focus on
      the medical history of affected parents. RESULTS: Twenty-three children with
      Alport syndrome from 21 different families were identified. Eight of 21 probands
      had family member(s) with renal symptoms attributed to other diseases. In these,
      a type IV collagen mutation was determined only after the manifestation of Alport
      syndrome in their child. One proband presented atypically with acute membrano
      proliferative glomerulo-nephritis. Only 3 out of 8 probands with a known family
      history of Alport syndrome had been intentionally screened for this disease. A
      COL4A5 mutation was found in 18 probands, COL4A3 in 2, and COL4A4 in 1. Each
      family showed private mutations; 17 out of 21 mutations were novel. CONCLUSIONS:
      Atypical presentation of Alport syndrome was quite common in mothers of our
      pediatric patients. To enable earlier diagnosis of Alport syndrome, nephrologists
      should look for a positive diagnosis in any patient with persistent renal
      symptoms, especially if there is a positive family history of (any) renal
      disease.

PMID- 30212820
TI  - Compatibility of Intravenous Fat Emulsion with Antibiotics for Secondary
      Piggyback Infusion.
AB  - BACKGROUND: The Guidelines for Parenteral and Enteral Nutrition in Japan state
      that parenteral fat emulsion can be infused through a secondary administration
      set. We tested the compatibility of fat emulsion with antibiotics in piggyback
      infusions in terms of changes in the size distribution of fat particles. METHODS:
      Test mixtures of 5% glucose solution, fat emulsion, and 25 antibiotic agents were
      prepared in the ratio appropriate for piggyback infusion (33: 10: 40) and
      analyzed serially for the number of fine particles by size using a light-shielded
      automatic fine particle counter. RESULTS: No marked changes were observed in the
      12 beta-lactam antibacterial drugs, clindamycin phosphate, teicoplanin,
      trimethoprim/sulfamethoxazole, and micafungin sodium even at 24 h after
      preparation. The particle size in the mixture containing vancomycin
      hydrochloride, levofloxacin hydrate, metronidazole, and fluconazole gradually
      increased after preparation. The particle size in the mixture containing
      gentamicin sulfate, arbekacin sulfate, minocycline hydrochloride, ciprofloxacin,
      and fosfomycin sodium changed significantly after preparation. CONCLUSIONS: The
      changes in the particle size observed with some drugs suggest that they may cause
      changes in the lipid particle size during administration and, therefore, those
      antibiotics agents should not be administered concurrently with fat emulsion.

PMID- 30212819
TI  - Prenatal Exposure to Persistent Organic Pollutants and Anogenital Distance in
      Children at 18 Months.
AB  - BACKGROUND: Anogenital distance (AGD) is a measure of in utero exposure to
      hormonally active agents. The aim of the present study was to evaluate the
      association between prenatal exposure to persistent organic pollutants (POPs) and
      AGD. METHODS: POP levels were measured in pregnant women, and the AGD was
      recorded in 43 offspring at 18 months. We used linear regression models to
      analyze the association between maternal POP exposure and offspring AGD. We
      defined the anogenital index (AGI) as AGD divided by weight at 18 months (AGI =
      AGD / weight at 18 months [mm/kg]) and included this variable in the regression
      models. RESULTS: AGI measure was 2.35 (0.61) and 1.38 (0.45) in males and
      females, respectively. AGI was inversely associated with lipid-adjusted
      concentrations of PBDE-99 (beta = -0.28, 95% confidence interval [CI]: -0.51, 
      0.04) and PBDE-153 (beta = -0.61, 95% CI: -1.11, -0.11) in males. We did not find
      any statistically significant relationship between any POPs and AGI in females.
      CONCLUSIONS: Environmental exposure to POPs may affect genital development and
      result in reproductive tract alterations with potentially relevant health
      consequences in maturity.

PMID- 30212822
TI  - The Fructose Hydrogen Breath Test: Nothing Behind the Sweet Fog?

PMID- 30212821
TI  - Observations of Bacterial Biofilm on Ureteral Stent and Studies on the
      Distribution of Pathogenic Bacteria and Drug Resistance.
AB  - OBJECTIVE: This study aims to observe the morphological characteristics of
      bacterial biofilm on the surface of ureteral stents and analyze distribution
      characteristics of pathogens on the bacterial biofilm and drug resistance.
      METHODS: Ureteral stents were sampled from 129 patients. A scanning electron
      microscope was used to observe the morphological characteristics of bacterial
      biofilms, and the Congo red medium was applied to screen bacterial biofilm
      strains on the renal pelvis section, ureter section, and bladder section
      respectively. Urine culture was performed, and the drug sensitive test analysis
      was carried out for the pathogenic bacteria detected. RESULTS: Bacterial biofilms
      can be observed on the surface of ureteral stents, and these bacteria are
      embraced by large amounts of fiber membranes. A total of 107 patients were found
      to be positive for biofilms with a positive rate of 82.9%. The positive rates of
      the bladder section, ureter section, renal pelvis section, and urine culture were
      85.0, 42.9, 67.3, and 24.3% respectively. Pathogenic bacteria mainly concentrated
      on Escherichia coli, and the drug resistance rate of the bacterial biofilm
      strains on the ureteral stent was relatively higher. CONCLUSION: The bacterial
      biofilm on the ureteral stent is an important factor that induces catheter
      associated urinary tract infections.

PMID- 30212823
TI  - Mechanical Thrombectomy in Acute Stroke Due to Carotid Occlusion: A Series of 153
      Consecutive Patients.
AB  - BACKGROUND: Strokes due to carotid artery occlusion (CAO) are associated with bad
      clinical prognosis and poor response to intravenous thrombolysis. Several studies
      in the past have shown the benefits of mechanical thrombectomy (MT) and compared
      bridging therapy (BT) and primary MT (PMT) in large vessel occlusions, but only a
      few studies have focused on the specific population of CAO and their response to
      endovascular treatment. METHODS: Retrospective review of patients treated at our
      center between January 2010 and June 2017 that (1) presented with acute ischemic
      stroke caused by CAO in the first 4.5 h since symptom onset, and (2) were treated
      with MT (BT or PMT). Baseline characteristics of the population, comparison
      between BT and PMT, intrahospital mortality, symptomatic intracranial hemorrhage,
      and functional outcome were investigated. RESULTS: A total of 153 patients were
      included. Baseline characteristics: 51.6% were male, and the median age was 71
      years. The most frequent risk factor was hypertension (71.9%). The main stroke
      etiology was atherothrombotic (40.5%). The mean admission National Institute of
      Health Severity Score (NIHSS) was 19, mean discharge NIHSS was 7. Isolated
      occlusion of the Extracranial or Intracranial Internal Carotid Artery was the
      most frequent occlusion location (52.3%). TICI 2b-3 was achieved in 87.6%,
      intrahospital mortality was 26.8%, symptomatic hemorrhage was 8.5%, and 3 months
      modified Rankin Score (mRS) 0-2 was 26.8%. Definitive carotid stenting was needed
      in 33.3% of the cases. BT versus PMT: Patients treated with PMT presented a
      higher incidence of atrial fibrillation, anticoagulation, and cardioembolic
      stroke compared to those treated with BT. No differences in TICI 2b-3, 3 months
      mRS or symptomatic hemorrhage were found between both groups. Intrahospital
      mortality: Poor perfusion-CT mismatch (p = 0.005), isolated Internal carotid
      artery location (p = 0.024), and symptomatic hemorrhage (p < 0.001) were
      independent predictors. Symptomatic intracranial hemorrhage: Patients with post
      treatment symptomatic hemorrhage had higher intrahospital mortality (p < 0.001)
      and worse 3 months-mRS (p = 0.033). Functional outcome: Admission NIHSS (p =
      0.012) independently predicted 3 months-mRS. CONCLUSIONS: In our population,
      patients with CAO clinically present with severe strokes. Isolated occlusions of
      the extra- or intracranial segments of the carotid are more frequent than tandem
      occlusions. Successful recanalization after thrombectomy is achieved in most of
      the patients, but association with favorable functional outcome is poor. Clinical
      evolution is similar in patients treated with PMT and BT. Intracranial
      symptomatic hemorrhage after treatment is associated with higher intrahospital
      mortality and worse 3 months-mRS. Poor perfusion-CT mismatch, symptomatic
      hemorrhage, and isolated CAO are independent predictors of intrahospital
      mortality. Admission NIHSS is an independent predictor of 3 months-mRS.

PMID- 30212824
TI  - The CircRNA-ACAP2/Hsa-miR-21-5p/ Tiam1 Regulatory Feedback Circuit Affects the
      Proliferation, Migration, and Invasion of Colon Cancer SW480 Cells.
AB  - BACKGROUND/AIMS: Circular RNAs (circRNAs), a type of RNA that is widely expressed
      in human cells, have essential roles in the development and progression of
      cancer. CircRNAs contain microRNA (miRNA) binding sites and can function as miRNA
      sponges to regulate gene expression by removing the inhibitory effect of an miRNA
      on its target gene. METHODS: We used the bioinformatics software TargetScan and
      miRanda to predict circRNA-miRNA and miRNAi-Mrna interactions. Rate of inhibiting
      of proliferation was measured using a WST-8 cell proliferation assay. Clone
      formation ability was assessed with a clone formation inhibition test. Cell
      invasion and migration capacity was evaluated by performing a Transwell assay.
      Relative gene expression was assessed using quantitative real-time polymerase
      chain reaction and relative protein expression levels were determined with
      western blotting. circRNA and miRNA interaction was confirmed by dual-luciferase
      reporter and RNA-pull down assays. RESULTS: In the present study, the miRNA hsa
      miR-21-5p was a target of circRNA-ACAP2, and T lymphoma invasion and metastasis
      protein 1 (Tiam1) was identified as a target gene of hsa-miR-21-5p. CircRNA-ACAP2
      and Tiam1 were shown to be highly expressed in colon cancer tissue and colon
      cancer SW480 cells, but miR-21-5p was expressed at a low level. SW480 cell
      proliferation was suppressed when the expression of circRNA-ACAP2 and Tiam1 was
      decreased and the expression of miR-21-5p was increased in vivo and in vitro.
      SW480 cell migration and invasion were also inhibited under the same
      circumstance. The circRNA-ACAP2 interaction regulated the expression of miR-21
      5p, and miR-21-5p regulated the expression of Tiam1. Down-regulation of circRNA
      ACAP2 promoted miR-21-5p expression, which further suppressed the transcription
      and translation of Tiam1. CONCLUSION: The present study shows that the circRNA
      ACAP2/hsa-miR-21-5p/Tiam1 regulatory feedback circuit could affect the
      proliferation, migration, and invasion of colon cancer SW480 cells. This was
      probably due to the fact that circRNA-ACAP2 could act as a miRNA sponge to
      regulate Tiam1 expression by removing the inhibitory effect of miR-21-5p on Tiam1
      expression. The results from this study have revealed new insights into the
      pathogenicity of colon cancer and may provide novel therapeutic targets for the
      treatment of colon cancer.

PMID- 30212826
TI  - Obstructive Sleep Apnea and Sudden Cardiac Death: Is the Landscape Clear?

PMID- 30212827
TI  - Interstitial Cells in the Pineal Gland of Pregnant and Nonpregnant Viscachas
      (Lagostomus maximus maximus): A Morphometric and Biochemical Study.
AB  - The pineal gland of mammals undergoes morphological and biochemical changes
      throughout the gestation period. In viscachas, a seasonal breeding rodent,
      pregnancy lasts approximately 154 days and 3 stages can be defined, i.e., early,
      mid, and late pregnancy. The purpose of this study is to analyze morphometric
      variations in the expression of S-100 protein, glial fibrillary acidic protein
      (GFAP), and vimentin in the interstitial cells (IC) in pregnant and nonpregnant
      viscachas by immunohistochemistry (IHC). We also aim to evaluate a probable
      relation between glandular activity and pregnancy. The immunopositive percentage
      area (%IA) for the studied proteins and the number of immunoreactive cells
      against the S-100 protein with a visible nucleus (no IC-S-100) were analyzed.
      Estradiol and progesterone serum levels were also determined by RIA. Variations
      in the expression of the S-100 protein and GFAP, as well as changes in the no IC
      S-100 related to serum hormone levels, were found between pregnant and
      nonpregnant viscachas. Viscachas in mid pregnancy exhibited the highest values of
      %IA for the analyzed proteins, followed by females in late and early pregnancy,
      while the nonpregnant ones showed the lowest values for all of the groups
      studied. Likewise, the no IC-S-100 also varied following the same pattern. Thus,
      these variations seem to indicate a direct relationship between glandular
      activity and gonadal hormone levels. On these grounds, we may conclude that IC
      undergo changes in relation to ovarian hormone levels and participate in the
      regulation of glandular activity during pregnancy. However, further research is
      necessary to elucidate this relationship.

PMID- 30212825
TI  - Total Flavonoids from Leaves of Carya Cathayensis Ameliorate Renal Fibrosis via
      the miR-21/Smad7 Signaling Pathway.
AB  - BACKGROUND/AIMS: Renal tubulointerstitial fibrosis is the most common pathway of
      progressive kidney injury, leading to end-stage renal disease. At present, no
      effective prophylactic treatment method is available. This study investigated the
      anti-fibrotic effects of total flavonoids (TFs) extracted from leaves of Carya
      Cathayensis in vivo and in vitro, and explored the underlying mechanisms.
      METHODS: Anti-fibrotic effects of TFs were measured using a mouse model of
      unilateral ureteral obstruction (UUO) and in transforming growth factor-beta1
      (TGF-beta1)-treated mouse tubular epithelial cells (mTECs). mRNA expression and
      protein levels of Collagen I, Collagen III, and alpha-smooth muscle actin (alpha
      SMA) were also tested by real-time reverse transcription PCR and western blot
      analysis. To elucidate the underlying mechanisms, expression of miR-21 was
      examined in mTECs treated with TFs using miR-21 mimics transfected into mTECs
      before TGF-beta1 and TFs treatment. Regulation of mothers against decapentaplegic
      homolog (Smad) signaling by miR-21 was subsequently validated via overexpression
      and deletion of miR-21 followed by a luciferase assay. RESULTS: TFs treatment
      attenuated renal fibrosis, and inhibited expression of collagens and alpha-SMA in
      the kidneys of mice subjected to UUO. In vitro, the TFs significantly decreased
      expression of fibrotic markers in TGF-beta1-treated mTECs. Moreover, TFs reduced
      miR-21 expression in a time- and dose-dependent manner in mTECs, increased
      expression of Smad7, and decreased phosphorylation of Smad3. Treatment with miR
      21 mimics abolished the anti-fibrotic effects of the TFs on the TGF-beta1-treated
      mTECs. In addition, genetic deletion of miR-21 upregulated expression of Smad7
      and suppressed phosphorylation of Smad3, attenuating renal fibrosis in mice.
      Bioinformatics predictions revealed the potential binding site of miR-21 in the
      3'-untranslated region of Smad7, and this was further confirmed by the luciferase
      assay. CONCLUSION: TFs ameliorate renal fibrosis via a miR-21/Smad7 signaling
      pathway, indicating a potential therapy for the prevention of renal fibrosis.

PMID- 30212828
TI  - The Optimal Management of Malignant Pleural Effusion: Steady Progress Towards an
      Evidence-Based Approach.

PMID- 30212829
TI  - Prognostic Significance of the Neutrophil/Lymphocyte Ratio in Patients with Non
      Human Papilloma Virus-Related Oropharyngeal Cancer: A Retrospective Cohort Study.
AB  - PURPOSE: To investigate the effects of the pretreatment neutrophil-to-lymphocyte
      ratio (N/L) on non-human papilloma virus (HPV)-related oropharyngeal cancer.
      MATERIALS AND METHODS: N/L was calculated by dividing the neutrophil count by the
      lymphocyte count. Survival outcomes were estimated using the Kaplan-Meier method
      and compared by the log-rank test. Univariate and multivariate analyses were
      performed to evaluate the prognostic impact of N/L and other clinical factors on
      survival outcomes. High/low N/L groups were defined as > 4.7 and <=4.7,
      respectively. RESULTS: Data of 57 consecutive patients with non-HPV-related
      oropharyngeal cancer were analyzed. The 3-year disease-free survival was 79
      versus 36.9% in favor of the low N/L group (p = 0.04). The 5-year overall
      survival was 71.6 versus 53.3% in the low N/L and high N/L group, respectively (p
      = 0.07). CONCLUSION: N/L could play an important role in non-HPV-related
      oropharyngeal cancer progression and indicate prognosis.

PMID- 30212830
TI  - Melatonin Attenuates Endothelial-to-Mesenchymal Transition of Glomerular
      Endothelial Cells via Regulating miR-497/ROCK in Diabetic Nephropathy.
AB  - BACKGROUND/AIMS: Endothelial-to-mesenchymal transition (EndMT) of glomerular
      endothelial cells (GEnCs) can induce albuminuria in diabetic nephropathy.
      Melatonin attenuates diabetic nephropathy, but its role and mechanism in EndMT of
      GEnCs in diabetic nephropathy remain unknown. METHODS: The effect of melatonin on
      EndMT induced by transforming growth factor (TGF)-beta2 in human renal GEnCs was
      determined by assaying the expression of endothelial marker cells (VE-cadherin
      and CD31) and mesenchymal cells (alpha-SMA and Snail), as well as monolayer
      permeability. The molecular mechanism of melatonin in these processes was focused
      on miR-497/ROCK signaling. Furthermore, the effect and mechanism of melatonin in
      EndMT were confirmed in glomeruli of rats with streptozotocin-induced diabetes.
      RESULTS: Melatonin increased expression of VE-cadherin and CD31 and inhibited
      alpha-SMA and Snail levels that were altered by TGF-beta2 in GEnCs. Melatonin
      treatment reduced expression and activity of ROCK1 and ROCK2, which suppressed
      TGF-beta2-induced hyperpermeability of GEnCs and EndMT of GEnCs. Melatonin
      reduced ROCK1 and ROCK2 expression and activity in TGF-beta2-stimulated GEnCs by
      enhancing expression of miR-497, which targets ROCK1 and ROCK2. Furthermore, we
      found that melatonin inhibited EndMT in glomeruli and albuminuria in rats with
      streptozotocin-induced diabetes. MiR-497 expression increased, whereas ROCK1 and
      ROCK2 expression and activity decreased in melatonin-treated diabetic rats.
      CONCLUSION: Melatonin attenuated EndMT of GEnCs via regulating miR-497/ROCK
      signaling in diabetic nephropathy. This study improves understanding of EndMT and
      the role of melatonin in diabetic nephropathy.

PMID- 30212831
TI  - A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate
      Homeostasis.
AB  - BACKGROUND/AIMS: Hyperphosphatemia is a serious complication of late-stage
      chronic kidney disease (CKD). Intestinal inorganic phosphate (Pi) handling plays
      an important role in Pi homeostasis in CKD. We investigated whether intestinal
      alkaline phosphatase 3 (Akp3), the enzyme that hydrolyzes dietary Pi compounds,
      is a target for the treatment of hyperphosphatemia in CKD. METHODS: We
      investigated Pi homeostasis in Akp3 knockout mice (Akp3-/-). We also studied the
      progression of renal failure in an Akp3-/- mouse adenine treated renal failure
      model. Plasma, fecal, and urinary Pi and Ca concentration were measured with
      commercially available kit, and plasma fibroblast growth factor 23, parathyroid
      hormone, and 1,25(OH)2D3 concentration were measured with ELISA. Brush border
      membrane vesicles were prepared from mouse intestine using the Ca2+ precipitation
      method and used for Pi transport activity and alkaline phosphatase activity. In
      vivo intestinal Pi absorption was measured with oral 32P administration. RESULTS:
      Akp3-/- mice exhibited reduced intestinal type II sodium-dependent Pi transporter
      (Npt2b) protein levels and Na-dependent Pi co-transport activity. In addition,
      plasma active vitamin D levels were significantly increased in Akp3-/- mice
      compared with wild-type animals. In the adenine-induced renal failure model, Akp3
      gene deletion suppressed hyperphosphatemia. CONCLUSION: The present findings
      indicate that intestinal Akp3 deletion affects Na+-dependent Pi transport in the
      small intestine. In the adenine-induced renal failure model, Akp3 is predicted to
      be a factor contributing to suppression of the plasma Pi concentration.

PMID- 30212832
TI  - The Telomerase and Alternative Lengthening of Telomeres Mechanisms Regulate
      Laryngeal Cancer Cell Apoptosis via the PI3K/Akt Pathway.
AB  - PURPOSE: To investigate the possible telomerase and alternative lengthening of
      telomeres (ALT) mechanisms influencing the apoptosis of laryngeal squamous cells.
      MATERIALS AND METHODS: The effects of the telomerase mechanism were observed by
      knockdown of human telomerase reverse transcriptase (hTERT). The ALT mechanism
      was induced by silencing related genes including TRF2, RAD51, and NBS1. Effects
      of telomerase and ALT mechanisms on tumor development were confirmed by xenograft
      tumors model. Tumor cell apoptosis was investigated by flow cytometry and Hoechst
      staining. Caspase-3 activity assay and Western blot were performed to investigate
      the possible mechanisms. RESULTS: After silencing ALT- and telomerase mechanism
      related genes, Bax and Bcl-2 were increased, and nuclear factor (NF)-kappaB
      translocation and PI3K/Akt phosphorylation were inhibited. CONCLUSIONS: The
      inhibition of telomere-related genes inhibited the growth of laryngeal squamous
      cell carcinoma by promoting cell apoptosis via the PI3K/Akt pathway.

PMID- 30212833
TI  - Effect of Provisioning on the Temporal Variation in the Activity Budget of Urban
      Long-Tailed Macaques (Macaca fascicularis) in West Sumatra, Indonesia.
AB  - We studied the behavioral ecology of provisioned long-tailed macaques (Macaca
      fascicularis) in Padang, West Sumatra, Indonesia, to examine how temporal changes
      in food provisioning within a day affect macaque activity. We conducted a field
      survey from October 2015 to January 2016 at two different sites: Gunung Meru (GM)
      and Gunung Padang (GP), where macaques receive high and low provisioning,
      respectively. The time budgets of macaques significantly differed between study
      groups. At GM, macaques spent more time resting, feeding, acting out agonistic
      behaviors, and less time moving and searching for food, than the macaques at GP.
      Diurnal activity patterns significantly changed within a day. The short-term
      change in activity of the macaques was closely related to the number of tourists:
      they spent a greater time feeding and searching when more tourists came to feed
      the monkeys, while time for grooming decreased. Our result showed that the
      ability of the macaques to adjust their activity in response to the number of
      tourists (that is, provisioning patterns) indicated their behavioral flexibility.
      Our result may aid the management strategies to reduce human-macaque conflicts,
      which has become a major problem in Padang.

PMID- 30212834
TI  - Application of 3D Printing for Patient-Specific Silicone Stents: 1-Year Follow-Up
      on 2 Patients.
AB  - Managing complex benign airway disease is a major challenge in interventional
      pulmonology. Airway stent placement can result in complications due to a variety
      of factors, including poor fit of the stent in the airway. We report the 1-year
      outcome of 2 patients with airway disease caused by granulomatosis with
      polyangiitis (Wegener's) affecting the left main bronchus and secondary carina.
      These patients had not responded to systemic therapy or standard bronchoscopic
      techniques and had complications with commercially available airway stents. We
      describe a first-in-human, clinical experience to address these issues. Using
      computed tomography (CT) imaging and 3D printing technology, we generated and
      implanted patient-specific silicone airway stents to address airway disease. 3D
      patient-specific stent prescription was created using a CT scan of the patient's
      chest and a proprietary software package originally developed for orthopedic
      surgical planning. Silicone stents were manufactured and implanted. Observation
      for > 1 year after implantation compared to the 6 months prior to patient
      specific stent implant were compared for the number, clinically required stent
      changes, procedure time, and general clinical improvement per usual standard of
      care after airway stenting. Patients showed improved durability, a shorter
      procedure time, and improvement of patient-reported symptoms leading to a reduced
      need for stent changes and modifications. The use of 3D printing technology to
      make patient-specific silicone stents is feasible with early clinical proof of
      concept noting a durable improvement over 1 year of follow-up.

PMID- 30212835
TI  - Intussusceptive Pillar Formation in Developing Porcine Glomeruli.
AB  - BACKGROUND/AIMS: Intussusceptive angiogenesis (IA) is a dynamic process which
      contributes to vascular expansion and remodeling. Intraluminal pillars have long
      been the distinctive structural indicator of IA. However, the mechanism of their
      formation has not been fully elucidated. METHODS: Using light and electron
      microscopy, we studied intussusceptive vascular growth in the developing porcine
      metanephric kidney. RESULTS: We observed intraluminal pillars formed by
      endothelial cells in the vasculature of developing glomeruli. Their diameter was
      < 2.5 um, consistent with the diameter of nascent pillars. TEM revealed that the
      majority of these pillars consisted only of endothelium. However, a central core
      of extracellular matrix (ECM) covered by endothelium, reminiscent of a more
      mature intussusceptive pillar, was also found in the lumen of a glomerular
      capillary. Perivascular cells or pericytes were not involved in the pillar
      structure during these stages of formation. CONCLUSION: This study shows ECM
      presence in a mature intussusceptive pillar without any perivascular cell
      involvement in the structure. This leads to the hypothesis that ECM deposition
      precedes the participation of these cells in the formation of intraluminal
      pillars during IA in porcine metanephric glomerular capillaries.

PMID- 30212836
TI  - Profile Shift in Latex Sensitization over the Last 20 Years.
AB  - BACKGROUND: Natural rubber latex (NRL) allergy is commonly diagnosed according to
      medical history, skin allergy tests, and serological analyses. However, skin
      tests are increasingly being abandoned because of (i) their time-consuming
      nature, (ii) latex preparations for skin tests being not commercially available,
      and (iii) the use of in-house prepared test solutions is becoming ever more
      difficult due to increasing regulatory hurdles. In this light, we have evaluated
      differences in the profiles of current and former patients with suspected latex
      allergy. METHODS: Sera of skin test-positive patients from a historic cohort
      (1995-2001, n = 149 patients) and currently (2014-2015, n = 48 patients) were
      simultaneously analyzed for specific IgE to latex by ImmunoCAP. If the
      serological screening was positive (>=0.35 kU/L), component-resolved diagnostics
      including profilins and cross-reactive carbohydrate determinants (CCDs) were
      performed. RESULTS: In contrast to 88% (131/149) of the skin test-positive
      patients from the 1990s, only 51.1% (24/47) of the current cohort were found
      positive for specific IgE to latex. While 48.3% (72/149) of the patients had a
      convincing positive history in the 1990s, current skin test-positive patients
      rarely reported a relevant medical history (8.5%, 4/47). Specific IgE levels to
      latex were significantly higher in former patients with suspected latex allergy
      (p < 0.001) than in former sensitized individuals without allergy. However, this
      significant difference was lost in current allergic and sensitized patients with
      positive skin tests. CONCLUSION: Sensitization profiles in patients with latex
      allergy have changed significantly over the last 2 decades. Discrimination
      between NRL sensitization and clinical allergy remains a diagnostic challenge.
      Our data highlight the need for a combination of all 3 criteria, i.e., patient
      history, skin test, and analysis of specific IgE, for a correct diagnosis of
      latex allergy.

PMID- 30212838
TI  - Brain oscillations, inhibition and social inappropriateness in frontotemporal
      degeneration.

PMID- 30212837
TI  - Role of Albumin Assay on Calcium Levels and Prescription of Phosphate Binders in
      Chronic Hemodialysis Patients.
AB  - BACKGROUND/AIMS: In hemodialysis (HD) patients, the bromcresol green (BCG) assay
      overestimates, whereas the bromcresol purple (BCP) assay underestimates albumin
      concentration. Since corrected calcium concentrations depend on albumin, the
      albumin assay may have implications for the management of bone mineral disorders.
      METHODS: A subset of patients from CONTRAST, a cohort of prevalent HD patients,
      was analyzed. Bone mineral parameters and prescription of medication were
      compared between patients in whom albumin was assessed by BCP versus BCG.
      RESULTS: Albumin was assessed by BCP in 331 patients (9 of 25 centers) and by BCG
      in 175 patients (16 of 25 centers). Albumin was the lowest in the BCP group (34.5
      +/- 4.2 vs. 40.3 +/- 3.1 g/L; p < 0.0005). Measured calcium levels and the
      prescription of calcium-based phosphate binders were similar in both groups.
      Corrected calcium levels, however, were markedly higher in the BCP group (2.45 +/
      0.18 vs. 2.33 +/- 0.18 mmol/L; p < 0.0005). CONCLUSION: These findings suggest
      that calcium levels are not corrected for albumin in clinical practice when
      considering the prescription of calcium-free or calcium-based phosphate-binders
      in dialysis patients.

PMID- 30212839
TI  - Apathy in rapid eye movement sleep behaviour disorder is associated with
      serotonin depletion in the dorsal raphe nucleus.
AB  - Apathy is a common and under-recognized disorder that often emerges in the
      prodromal phase of Parkinsonian diseases. The mechanism by which this occurs is
      not known, but recent evidence from patients with established Parkinson's disease
      suggests that serotonergic dysfunction may play a role. The integrity of the
      raphe serotonergic system can be assessed alongside dopaminergic basal ganglia
      imaging using the radioligand 123I-ioflupane, which binds both serotonin and
      dopamine transporters. To investigate the relative roles of these
      neurotransmitters in prodromal parkinsonism, we imaged patients with idiopathic
      rapid eye movement sleep behaviour disorder, the majority of whom will develop a
      parkinsonian disorder in future. Forty-three patients underwent brain imaging
      with 123I-ioflupane single photon emission computed tomography and structural
      MRI. Apathy was quantified using the Lille Apathy Rating Scale. Other clinical
      parkinsonian features were assessed using standard measures. A negative
      correlation was observed between apathy severity and serotonergic 123I-ioflupane
      signal in the dorsal raphe nucleus (r = -0.55, P < 0.001). There was no
      significant correlation between apathy severity and basal ganglia dopaminergic
      signal, nor between dorsal raphe signal and other neuropsychiatric scores. This
      specific association between apathy and raphe 123I-ioflupane signal suggests that
      the serotonergic system might represent a target for the treatment of apathy.

PMID- 30212840
TI  - Quality and Quantity in Kidney Cancer Surgery: The Role of Nonneoplastic Kidney
      and Kidney Volumetrics in Predicting Postoperative Renal Function.
AB  - Objectives: To model renal function 2 years following radical nephrectomy with
      quantitative analyses using clinical, histopathologic, and renal composite
      cortical volumes (CCV). Methods: This retrospective study involved an assessment
      of the nonneoplastic kidney tissue by three blinded nephropathologists using
      modified Banff 1997 criteria for renal allograft pathology. Volumetric image
      acquisition was obtained by three independent radiologists using preoperative
      imaging. A 2-year estimated glomerular filtration (eGFR) calculator was created.
      Results: Among the 126 patients, median age was 60 years; median CCV, 398.1 cm3;
      preoperative eGFR, 77 mL/min/1.73 m2; and 2-year postoperative eGFR, 54
      mL/min/1.73 m2. Of the subjects, 64% had hypertension, 26% diabetes, and 37% were
      smokers. Increasing age, glomerulopathy/sclerosis, tubulointerstitial scarring,
      and arteriosclerosis were statistically significantly and adversely associated
      with eGFR. Conversely, increasing CCV was associated with a higher eGFR.
      Conclusions: Quantitative analysis of the nephrectomized kidney in conjunction
      with patient age can accurately predict renal function at 2 years.

PMID- 30212841
TI  - Genome-wide identification of FOXL2 binding and characterization of FOXL2
      feminizing action in the fetal gonads.
AB  - The identity of the gonads is determined by which fate, ovarian granulosa cell or
      testicular Sertoli cell, the bipotential somatic cell precursors choose to
      follow. In most vertebrates, the conserved transcription factor FOXL2 contributes
      to the fate of granulosa cells. To understand FOXL2 functions during gonad
      differentiation, we performed genome-wide analysis of FOXL2 chromatin occupancy
      in fetal ovaries and established a genetic mouse model that forces Foxl2
      expression in the fetal testis. When FOXL2 was ectopically expressed in the
      somatic cell precursors in the fetal testis, FOXL2 was sufficient to repress
      Sertoli cell differentiation, ultimately resulting in partial testis-to-ovary sex
      reversal. Combining genome-wide analysis of FOXL2 binding in the fetal ovary with
      transcriptomic analyses of our Foxl2 gain-of-function and previously published
      Foxl2 loss-of-function models, we identified potential pathways responsible for
      the feminizing action of FOXL2. Finally, comparison of FOXL2 genome-wide
      occupancy in the fetal ovary with testis-determining factor SOX9 genome-wide
      occupancy in the fetal testis revealed extensive overlaps, implying that
      antagonistic signals between FOXL2 and SOX9 occur at the chromatin level.

PMID- 30212842
TI  - Lemons and Lyme.

PMID- 30212843
TI  - Searching for the Immature Stages of Ixodes scapularis (Acari: Ixodidae) in Leaf
      Litter and Soil in Texas.
AB  - The standard tick collection methods of flagging and dragging are successful for
      collecting all stages of the blacklegged tick, Ixodes scapularis (Say) (Acari:
      Ixodidae), in the northern United States. However, for unknown reasons, these
      methods are unsuccessful for collecting the immature stages of I. scapularis in
      the southern United States. Thus, a different collection strategy was employed to
      search for the immature stages of I. scapularis in the southern state of Texas.
      Monthly sampling of three types of microhabitats potentially harboring ticks was
      conducted for 17 mo at the Big Thicket National Preserve. Samples of leaf litter,
      topsoil, and subsoil were placed within Berlese funnels to determine if the
      immature stages of I. scapularis are residing in these layers. No ticks were
      found in any of the 600 substrate samples examined. Along nearby trail edges in
      the same area, 656 adult I. scapularis (an average of 22.6 per 1,000 m2), as well
      as 268 immatures of other species (i.e., Amblyomma americanum (Linnaeaus) (Acari:
      Ixodidae) and Dermacentor variabilis (Say) (Acari: Ixodidae)) were collected
      using flagging and dragging. These results suggest that unlike speculations from
      previous studies in the southern United States, the immature stages of I.
      scapularis may not be residing in the leaf litter and soil layers in Texas. We
      hypothesize that they may be residing in their host's nests and burrows. Perhaps
      I. scapularis in the south is exhibiting a stage specific mixed host-seeking
      strategy by residing in nests and burrows as immatures, contributing to the
      geographical difference in Lyme disease prevalence between the northern and
      southern United States.

PMID- 30212844
TI  - Smokers Display Reduced Glucocorticoid Sensitivity Prior to Symptomatic Chronic
      Disease Development.
AB  - Background: Chronic stress plays a critical role in many of today's diseases and
      causes of death. Tobacco use reliably increases the likelihood of chronic disease
      development and premature death. In addition, habitual tobacco use elevates risk
      of chronic inflammatory diseases, and glucocorticoid therapy is often less
      effective in smokers compared with nonsmokers. Taken together, smokers may
      develop glucocorticoid insensitivity, thereby removing the body's greatest anti
      inflammatory mechanism. Purpose: The purpose of this study was to examine
      glucocorticoid sensitivity among 24 smokers and 24 age-, sex-, and body mass
      index-matched never smokers who were clinically healthy individuals (i.e., no
      diagnosis or medication use for chronic diseases and normotensive). Method:
      Participants visited the lab after a 12 hr fast, provided a blood sample, and
      completed a series of psychosocial questionnaires. Smokers continued smoking ad
      libitum before the lab visit. Group differences in glucocorticoid sensitivity
      were examined using ANCOVA and repeated with linear mixed model to account for
      possible dependence among immune outcomes that matching participants on age, sex,
      and body mass index may have introduced. Results: Prior to clinical disease
      onset, smokers' peripheral blood mononuclear cells (PBMCs) exhibited reduced
      glucocorticoid sensitivity as well as a diminished inflammatory response to
      lipopolysaccharide compared with never smokers' PBMCs; results were identical
      regardless of statistical modeling used. Conclusions: Cigarette smoking, a self
      initiated pharmacological chronic stressor, may provide a unique opportunity to
      examine early wear and tear on physiological functioning that may lead to chronic
      disease development. Additional research into PBMCs' intracellular changes must
      be examined as well as repeating this study in a larger, more heterogeneous
      population.

PMID- 30212845
TI  - Open-label Placebos for Wound Healing: A Randomized Controlled Trial.
AB  - Background: Open-label placebos are a novel treatment option, in which
      participants take placebos with full knowledge that they do not contain active
      medicine. Open-label placebo treatments have been shown to result in patient
      reported symptom improvements, but they have not been tested on objectively
      measurable physiological outcomes such as wound healing. Purpose: The current
      study aimed to determine whether open-label placebos improved wound healing in
      punch biopsy wounds compared with no treatment. Methods: In a randomized
      controlled trial, 70 participants (mean age 27.6 +/- 10.1, 58 female) were
      provided with information about the beneficial effects of placebos and given a 4
      mm punch biopsy wound. Participants were then randomized to either an open-label
      placebo intervention (two placebo tablets twice a day for 10 days) or a no
      treatment control group. Wounds were photographed at 7 days and 10 days to
      determine reepithelialization of the wound surface. Results: No significant
      differences were observed between the open-label placebo and control conditions
      in the percentage of wound area healed or for the number of participants with
      fully reepithelialized wounds at 7 days (placebo 7/32 wounds healed, control
      10/33 wounds healed, (chi2[1, N = 65] = 0.60, p = .440, phi = 0.10) and 10 days
      after wounding (placebo 17/32, control 25/33 wounds healed (chi2[1, N = 65] =
      3.64, p = .056, phi = 0.24). Conclusions: Open-label placebo treatment does not
      improve the healing rate of wounds. Open-label placebos may be beneficial for
      subjective patient-reported outcomes but do not influence wound healing.
      Australian New Zealand Clinical Trials Registration: ACTRN12616000411448.

PMID- 30212846
TI  - Connectionism and Behavioral Clusters: Differential Patterns in Predicting
      Expectations to Engage in Health Behaviors.
AB  - Background: The traditional approach to health behavior research uses a single
      model to explain one behavior at a time. However, health behaviors are
      interrelated and different factors predict certain behaviors better than others.
      Purpose: To conceptualize groups of health behaviors as memory events that elicit
      various beliefs. A connectionist approach was used to examine patterns of
      construct activation related to expectations to engage in health behavior
      clusters. Methods: A sample of lay people (N = 1,709) indicated their
      expectations to perform behaviors representing four clusters (Risk Avoidance,
      Nutrition & Exercise, Health Maintenance, and General Well-Being) and rated them
      on 14 constructs obtained from health behavior literature. Results: Expectations
      to engage in all behavioral clusters were significantly and positively associated
      with "frequency of performance," "perceived behavioral control," and "anticipated
      regret," and negatively associated with "effort." However, each behavioral
      cluster was also predicted by activation of a unique pattern of predictors.
      Conclusions: A connectionist approach can be useful for understanding how
      different patterns of constructs relate to specific outcomes. The findings
      provide a rationale for lay people's cognitive schema of health behaviors, with
      each behavioral cluster possessing characteristics associated with distinct
      predictors of expectations to engage in it. These unique activation patterns
      point to factors that may be particularly significant for health interventions
      targeting different clusters of health behaviors.

PMID- 30212847
TI  - Social Isolation Predicts Frequent Attendance in Primary Care.
AB  - Background: Frequent attenders in primary care have complex physical and mental
      healthcare needs as well as low satisfaction with their health care.
      Interventions targeting mental health or psychoeducation have not been effective
      in reducing attendance. Here, we test the proposition that both frequent
      attendance and poor health are partly explained by unmet social needs (i.e.,
      limited social group support networks). Methods: Study 1 (N = 1,752) was a large,
      cross-sectional community sample of primary care attenders in Scotland. Study 2
      (N = 79) was a longitudinal study of a group of young people undergoing a life
      transition (moving countries and commencing university) that increased their risk
      of frequent attendance. Study 3 (N = 46) was a pre-post intervention study
      examining whether disadvantaged adults who joined a social group subsequently had
      reduced frequency of primary care attendance. Results: All three studies found
      that low social group connectedness was associated with a higher frequency of
      primary care attendance. This was not attributable to poorer health among those
      who were socially isolated. In Study 3, joining a social group led to reduced
      primary care attendance to the extent that participants experienced a
      (subjective) increase in their social group connectedness. Conclusions: Unmet
      social needs among frequent attenders warrant closer consideration. Interventions
      that target social group connectedness show promise for reducing overutilization
      of primary care services.

PMID- 30212848
TI  - Efficacy of Online Multi-Player Versus Single-Player Exergames on Adherence
      Behaviors Among Children: A Nonrandomized Control Trial.
AB  - Background: Exergames have the potential to significantly increase physical
      activity in children. Studies to date have shown mixed results and often rely on
      self-reported data. Multi-player gaming may augment participation. Purpose: The
      purpose of the study was to examine children's adherence behaviors in multi
      player online exergames compared to a single-player condition within a home
      environment. Methods: Seventy-two children, aged 9-12 years, who were not meeting
      physical activity guidelines at baseline, were allocated to the multi-player or
      single-player condition. Six-week cycle-based exergaming trials took place 5
      day/week in the early evening with online game supervision. Bike use was
      objectively recorded via game logs. Results: Adherence was high throughout the
      trial. Play session duration was M = 37.65 (SD = 15.39) min/day, and overall play
      duration was M = 133.45 (SD = 81.27) min in Week 1 and M = 77.23 (SD = 84.09) min
      in Week 6. Total physical activity was significantly higher at 6 weeks compared
      to baseline (p = .01, etap2 = .13). There was no significant difference in play
      duration between conditions (p = .57, etap2 = .01). Conclusion: This trial
      objectively demonstrated that exergames can promote high adherence levels. Multi
      player capabilities did not augment adherence levels. Introducing new games
      throughout the trial may have motivated participants to keep playing, regardless
      of whether play was against real or artificial opponents. Weekly play duration
      decreased due to a significant drop in play frequency. For children who enjoy
      exergames, innovative solutions to promote more frequent exergame play are
      needed. Clinical This Registration: NCT02032667.

PMID- 30212849
TI  - A Randomized Controlled Trial of an Optimized Smoking Treatment Delivered in
      Primary Care.
AB  - Background: The effectiveness of smoking cessation treatment is limited in real
      world use, perhaps because we have not selected the components of such treatments
      optimally nor have treatments typically been developed for and evaluated in real
      world clinical settings. Purpose : To validate an optimized smoking cessation
      treatment package that comprises intervention components identified as effective
      in factorial screening experiments conducted as per the Multiphase Optimization
      Strategy (MOST). Methods: Adult smokers motivated to quit were recruited from
      primary care clinics (N = 623). Participants were randomized to receive either
      recommended usual care (R-UC; 10 min of in-person counseling, 8 weeks of nicotine
      patch, and referral to quitline services) or abstinence-optimized treatment (A
      OT; 3 weeks of prequit mini-lozenges, 26 weeks of nicotine patch + mini-lozenges,
      three in-person and eight phone counseling sessions, and 7-11 automated calls to
      prompt medication use). The key outcomes were self-reported and biochemically
      confirmed (carbon monoxide, CO <6 ppm) 7-day point-prevalence abstinence.
      Results: A-OT participants had significantly higher self-reported abstinence
      rates than R-UC participants at 4, 8, 16, and 26 weeks (ORs: 1.91-3.05; p <.
      001). The biochemically confirmed 26-week abstinence rates were lower than the
      self-reported 26-week rates, but revealed a similar treatment effect size (OR =
      2.94, p < .001). There was no moderation of treatment effects on 26-week
      abstinence by demographic, psychiatric, or nicotine dependence variables. A-OT
      had an incremental cost-effectiveness ratio for 26-week CO-confirmed abstinence
      of $7,800. Conclusions: A smoking cessation treatment that is optimized via MOST
      development meaningfully enhances cessation rates beyond R-UC smoking treatment
      in smokers seen in primary care. Clinical Trial Registration: NCT02301403.

PMID- 30212851
TI  - Diagnostic value of longitudinal flow gradient for the presence of
      haemodynamically significant coronary artery disease.
AB  - Aims: The longitudinal myocardial blood flow (MBF) gradient derived from positron
      emission tomography (PET) has been proposed as an emerging non-invasive index of
      haemodynamically significant coronary artery disease (CAD). This study aimed to
      investigate the diagnostic value of longitudinal MBF gradient for the presence of
      haemodynamically significant CAD. Methods and results: A total of 204 patients
      (603 vessels) with suspected CAD underwent [15O]H2O PET followed by invasive
      coronary angiography with fractional flow reserve (FFR) of all major coronary
      arteries. Longitudinal base-to-apex MBF gradients were assessed by two methods,
      using MBF in apical and mid (Method 1) or in apical and basal (Method 2)
      myocardial segments to calculate the gradient. The hyperaemic longitudinal MBF
      gradient was only weakly correlated with FFR (Method 1: r = 0.12, P = 0.02;
      Method 2: r = 0.22, P < 0.001). The hyperaemic longitudinal MBF gradient (by both
      methods), had lower diagnostic value when compared with hyperaemic MBF for the
      presence of haemodynamically significant CAD, defined as an FFR <= 0.80. No
      significant correlations between longitudinal MBF gradients and FFR were noted in
      proximal lesions, whereas longitudinal MBF gradients and FFR were significantly
      correlated in non-proximal lesions (r = 0.57, P < 0.001). Conclusion: PET
      measured longitudinal flow parameters had lower diagnostic value when compared
      with hyperaemic MBF for the presence of haemodynamically significant CAD. Since
      lesion location was found to affect the correlation of PET measured longitudinal
      flow parameters and FFR, presence of a longitudinal flow gradient may be partly
      caused by normalization to a relatively normal perfused areas.

PMID- 30212852
TI  - Updating the determinants of health model in the Information Age.
AB  - In 1991, Dahlgren and Whitehead produced a highly influential model of the
      determinants of health that has since been used by numerous national and
      international public health organizations globally. The purpose of the model is
      to enable interventions that improve health to be addressed at four key policy
      levels. It is not a model of health or disease; instead the model is structured
      around health policy decision-making. However the model needs an update, since it
      was devised there has been a digital revolution that has transformed every aspect
      of: human life, our cities, society and the fundamental principles upon which the
      global economy operates. The article examines the impact of Information and
      Communication Technologies (ICT) on the determinants of health. ICT has given
      rise to a new Information Age that is implicated in many of the major global
      health issues today. Addressing contemporary health issues requires intervention
      at the level of ICT, particularly as health communication online is central to
      the delivery and dissemination of public health policies.

PMID- 30212850
TI  - Adverse Childhood Experiences and Symptoms of Urologic Chronic Pelvic Pain
      Syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain
      Research Network Study.
AB  - Background: Adverse Childhood Experiences (ACEs) such as sexual and physical
      violence, serious illness, and bereavement have been linked to number of chronic
      pain conditions in adulthood, and specifically to urologic chronic pelvic pain
      syndrome (UCPPS). Purpose: We sought to characterize the prevalence of ACEs in
      UCPPS using a large well-characterized cohort in comparison with a group of
      healthy controls. We also sought to determine the association of ACE severity
      with psychological factors known to impact pain and to determine whether ACEs are
      associated with patterns of improvement or worsening of symptom over a year of
      naturalistic observation. Methods: For longitudinal analyses we used functional
      clusters identifying broad classes of (a) improved, (b) worsened, and (c) stable
      groups for genitourinary pain and urinary symptoms. We employed a mediation/path
      analysis framework to determine whether ACEs influenced 1 year outcomes directly,
      or indirectly through worse perceptions of physical well-being. Results: ACE
      severity was elevated in UCPPS (n = 421) participants compared with healthy
      controls (n = 414; p < .001), and was most strongly associated with factors
      associated with complex chronic pain, including more diffuse pain, comorbid
      functional symptoms/syndromes, and worse perceived physical well-being (all p <
      .001). Finally, worse physical well-being mediated the relationship between ACE
      severity and less likelihood of painful symptom improvement (OR = .871, p =
      .007)) and a greater likelihood of painful symptom worsening (OR = 1.249, p =
      .003) at 1 year. Conclusions: These results confirm the association between ACEs
      and UCPPS symptoms, and suggest potential targets for therapeutic interventions
      in UCPPS. Clinical Trial registration: NCT01098279.

PMID- 30212853
TI  - Developmental and cancer-associated plasticity of DNA replication preferentially
      targets GC-poor, lowly expressed and late-replicating regions.

PMID- 30212854
TI  - Cretaceous asterid evolution: fruits of Eydeia jerseyensis sp. nov. (Cornales)
      from the upper Turonian of eastern North America.
AB  - Background and aims: The asterids (>80 000 extant species) appear in the fossil
      record with considerable diversity near the Turonian-Coniacian boundary (~90 Ma;
      Late Cretaceous) and are strongly represented in the earliest diverging lineage,
      Cornales. These early asterid representatives have so far been reported from
      western North America and eastern Asia. In this study, we characterize a new
      cornalean taxon based on charcoalified fruits from the upper Turonian of eastern
      North America, a separate landmass from western North America at the time, and
      identify early palaeobiogeographical patterns of Cornales during the Cretaceous.
      Methods: Fossils were studied and imaged using scanning electron microscopy and
      micro-computed tomography (micro-CT) scanning. To assess the systematic
      affinities of the fossils, phylogenetic analyses were conducted using maximum
      parsimony.  Key results : The charcoalified fruits are represented by tri-locular
      woody endocarps with dorsal apically opening germination valves. Three septa
      intersect to form a robust central axis. Endocarp ground tissue consists of two
      zones: an outer endocarp composed of isodiametric sclereids and an inner endocarp
      containing circum-locular fibres. Central vasculature is absent; however, there
      are several small vascular bundles scattered within the septa. Phylogenetic
      analysis places the new taxon within the extinct genus Eydeia. Discussion: Thick
      walled endocarps with apically opening germination valves, no central vascular
      bundle and one seed per locule are indicative of the order Cornales. Comparative
      analysis suggests that the fossils represent a new species, Eydeia jerseyensis
      sp. nov. This new taxon is the first evidence of Cornales in eastern North
      America during the Cretaceous and provides insights into the palaeobiogeography
      and initial diversification of the order.

PMID- 30212855
TI  - Cohort Profile: The Finnish Health in Teens (Fin-HIT) study: a population-based
      study.

PMID- 30212856
TI  - Non-conventional yeast cell factories for sustainable bioprocesses.
AB  - The non-conventional yeasts Kluyveromyces lactis, Yarrowia lipolytica, Ogataea
      polymorpha and Pichia pastoris have been developed as eukaryotic expression hosts
      because of their desirable growth characteristics, including inhibitor and thermo
      tolerance, utilisation of diverse carbon substrates and high amount of
      extracellular protein secretion. These yeasts already have established in the
      heterologous production of vaccines, therapeutic proteins, food additives and bio
      renewable chemicals, but recent advances in the genetic tool box have the
      potential to greatly expand and diversify their impact on biotechnology. The
      diversity of these yeasts includes many strains possessing highly useful, and in
      some cases even uncommon, metabolic capabilities potentially helpful for the
      bioprocess industry. This review outlines the recent updates of non-conventional
      yeast in sustainable bioprocesses.

PMID- 30212858
TI  - Late lumen loss in the era of new generation drug-eluting stents: perspective on
      a quarter century companion.

PMID- 30212857
TI  - Sex differences in calcified plaque and long-term cardiovascular mortality:
      observations from the CAC Consortium.
AB  - Aims : Pathologic evidence supports unique sex-specific mechanisms as precursors
      for acute cardiovascular (CV) events. Current evidence on long-term CV risk among
      women when compared with men based on measures of coronary artery calcium (CAC)
      remains incomplete. Methods and results : A total of 63 215 asymptomatic women
      and men were enrolled in the multicentre, CAC Consortium with median follow-up of
      12.6 years. Pooled cohort equation (PCE) risk scores and risk factor data were
      collected with the Agatston score and other CAC measures (number of lesions and
      vessels, lesion size, volume, and plaque density). Cox proportional hazard models
      were employed to estimate CV mortality (n = 919). Sex interactions were
      calculated. Women and men had average PCE risk scores of 5.8% and 9.1% (P <
      0.001). Within CAC subgroups, women had fewer calcified lesions (P < 0.0001) and
      vessels (P = 0.017), greater lesion size (P < 0.0001), and higher plaque density
      (P = 0.013) when compared with men. For women and men without CAC, long-term CV
      mortality was similar (P = 0.67), whereas detectable CAC was associated with 1.3
      higher hazard for CV death among women when compared with men (P < 0001).
      Cardiovascular mortality was higher among women with more extensive, numerous, or
      larger CAC lesions. The relative hazard for cardiovascular disease (CVD)
      mortality for women and men was 8.2 vs. 5.1 for multivessel CAC, 8.6 vs. 5.9 for
      >=5 CAC lesions, and 8.5 vs. 4.4 for a lesion size >=15 mm3, respectively.
      Additional explorations revealed that women with larger sized and more numerous
      CAC lesions had 2.2-fold higher CVD mortality (P < 0.0001) as compared to men.
      Moreover, CAC density was not predictive of CV mortality in women (P = 0.51) but
      was for men (P < 0.001), when controlling for CAC volume and cardiac risk
      factors. Conclusion: Our overall findings support that measures beyond the
      Agatston score provide important clues to sex differences in atherosclerotic
      plaque and may further refine risk detection and focus preventive strategies of
      care.

PMID- 30212859
TI  - First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney
      Transplant Recipient.
AB  - Cestodes are emerging agents of severe opportunistic infections among
      immunocompromised patients. We describe the first case of human infection, with
      the recently-proposed genus Versteria causing an invasive, tumor-like hepatic
      infection with regional and distant extension in a 53-year-old female kidney
      transplant recipient from Atlantic Canada.

PMID- 30212860
TI  - Reply: Brain oscillations, inhibition and social inappropriateness in
      frontotemporal degeneration.

PMID- 30212861
TI  - Depressive Symptomatology in School-Aged Children with Obstructive Sleep Apnea
      Syndrome: Incidence, Demographic Factors, and Changes Following a Randomized
      Controlled Trial of Adenotonsillectomy.
AB  - Study Objectives: Depressive symptoms following adenotonsillectomy (AT) relative
      to controls were examined in children with OSAS. Methods : The Childhood
      Adenotonsillectomy Trial (CHAT) multisite study examined the impact of AT in 453
      children aged 5 to 9.9 years with polysomnographic evidence of OSAS without
      prolonged desaturation, randomized to early adenotonsillectomy (eAT) or watchful
      waiting with supportive care (WWSC). 176 children (eAT n=83; WWSC n=93) with
      complete evaluations for depressive symptomatology between baseline and after a 7
      month intervention period were included in this secondary analysis. Results:
      Exact binomial test assessed proportion of depressive symptomatology relative to
      norms, while effects of AT and OSAS resolution were assessed through linear
      quantile mixed-models. Treatment group assignment did not significantly impact
      depression symptoms, although self-reported depression symptoms improved over
      time (p<0.001).  Resolution of OSAS symptoms demonstrated a small interaction
      effect in an unexpected direction, with more improvement in parent ratings of
      anxious/depressed symptoms for children without resolution (p=0.030). Black
      children reported more severe depressive symptoms (p=0.026) and parents of
      overweight/obese children reported more withdrawn/depressed symptoms (p=0.004). 
      Desaturation nadir during sleep was associated with self-report depressed (r=
      0.17, p=0.028), parent-reported anxious/depressed (r=-0.15, p=0.049), and
      withdrawn/depressed (r=-0.24, p=0.002) symptoms. Conclusions: Increased risk for
      depressed and withdrawn/depressed symptoms was detected among children with OSAS,
      and different demographic variables contributed to risk in self-reported and
      parent-reported depression symptoms. Arterial oxygen desaturation nadir during
      sleep was strongly associated with depressed symptoms. However, despite
      improvements in child-reported depressed symptoms over time, changes were
      unrelated to either treatment group or OSAS resolution status.

PMID- 30212862
TI  - Temporal variability in the allergenicity of airborne Alternaria spores.
AB  - The concentration of fungal spores in the air is traditionally considered as a
      proxy of allergen exposure. However, in vitro experiments have shown that the
      allergenicity of Alternaria spores varies depending on ecophysiological and
      developmental factors. Despite the potential clinical significance of these
      findings, it has never been verified in outdoor environments. This study,
      therefore, aims to investigate variability in the amount of the major allergen
      (Alt a 1) released from Alternaria spores in outdoor air. During the 3-year
      monitoring study (2014-2016), the median seasonal allergenicity of Alternaria
      spores exceeded 8.6 * 10-3 pg Alt a 1/spore. The most allergenic spores were
      collected during the driest and the most polluted season (with respect to
      seasonal concentrations of ozone, sulphur dioxide, and particulate matter).
      Within the season, daily spore allergenicity ranged from 2.4 to 34.7 * 10-3 pg
      Alt a 1/spore (5th-95th percentile). No repeatable effects of weather and
      pollution on short-term variations in Alternaria spore allergenicity were found.
      However, during the episodes when high-potency spores were recorded, the air
      masses arrived from eastern directions. Contrary, the spores with the lowest
      allergenicity were related to western winds. This suggests that factors such as
      source area (habitat types) and species diversity could be responsible for the
      varying exposure to Alternaria allergens. Our findings show that high and low
      potency spores are recorded in the air; therefore, the airborne concentrations of
      fungal spores alone may not be sufficient to provide allergy sufferers and
      healthcare professionals with information about allergen exposure.

PMID- 30212863
TI  - Brood Affects Hygienic Behavior in the Honey Bee (Hymenoptera: Apidae).
AB  - Despite receiving much attention, the ectoparasitic mite Varroa destructor
      (Anderson and Trueman) and the pathogens it vectors remain critical threats to
      the health of the honey bee Apis mellifera (Linnaeus) (Hymenoptera: Apidae). One
      promising intervention approach is the breeding of hygienic honey bees, which
      have an improved ability to detect and remove unhealthy brood from the colony,
      and are thus more resistant to Varroa. While much hygienic behavior-related
      research has focused on enhanced adult honey bee olfaction, less attention has
      been paid to the olfactory signals that originate inside the brood cell,
      triggering hygienic removal. Here, we hypothesized that selection for hygienic
      behavior in honey bees has influenced brood signaling, predicting that: 1) in a
      common social environment, removal rates differ among brood with different
      selective breeding histories, and 2) the removal rates of brood positively
      correlate to the hygiene level of the brood's colony of origin. To test these
      predictions, we cross-fostered brood subjected to control, wound, or Varroa
      treatment in unselected (UNS), Minnesota Hygienic (HYG), and Varroa-Sensitive
      Hygienic (VSH) colonies, and monitored individual brood cells for hygienic
      removal. Results confirmed both predictions, as brood from hygienic colonies was
      more likely to be removed than brood from UNS colonies, regardless of where the
      brood was fostered. These findings suggest that hygiene-related brood signals
      complement previously identified characteristics of hygienic adults, constituting
      an important mechanism of social immunity in honey bees. Thus, selective breeding
      for honey bee hygienic behavior may be improved through the utilization of field
      assays containing compounds related to larval signaling.

PMID- 30212864
TI  - Reply to Boning.

PMID- 30212865
TI  - Commentary on: The Impact on Mortality and Societal Costs From Smoking Cessation
      in Aesthetic Plastic Surgery in the United States.

PMID- 30212866
TI  - Replication-dependent histone isoforms: a new source of complexity in chromatin
      structure and function.

PMID- 30212867
TI  - A Proposal for Separation of Nuclear Atypia and Architectural Atypia in Bethesda
      Category III (AUS/FLUS) Based on Differing Rates of Thyroid Malignancy.
AB  - Objectives: Bethesda category III (atypia of undetermined significance/follicular
      lesion of undetermined significance) includes sparsely cellular specimens with
      nuclear atypia (3N) and/or architectural atypia (3A). This study investigates
      whether the two types of atypia have different rates of malignancy (ROMs).
      Methods: Cytologic and histologic diagnoses of resected thyroid nodules were
      recorded. ROM was calculated for all Bethesda categories and for 3N and 3A
      subcategories. Possible noninvasive follicular thyroid neoplasms with papillary
      like nuclear features were reviewed and removed from malignancies, and ROM was
      recalculated. Results: A total of 1,396 nodules were included. ROM of 3N (33.3%
      26.0%) was higher than 3A (7.7%-5.0%) (P < .0001) and was similar to suspicious
      for follicular neoplasm (25.0%-20.3%) (P = .3). ROM of 3A approached benign (2.4%
      1.5%) (P = .02). Conclusions: Strong consideration should be given to separating
      3N (nuclear atypia with higher risk for papillary thyroid carcinoma) from 3A
      (architectural atypia with higher chance of being benign) to convey different
      ROMs.

PMID- 30212868
TI  - Methodological quality assessment of network meta-analysis of drug interventions:
      implications from a systematic review.
AB  - Background: We aimed to determine the methodological quality of network meta
      analyses (NMAs) and their compliance with reporting guidelines. Methods: A
      systematic review of NMAs comparing any pharmacological interventions was
      performed (searches in Medline and Scopus). The characteristics of NMAs were
      collected by two independent reviewers. We applied R-AMSTAR to all NMAs,
      generating a methodological quality score that could range from 11 to 44 points.
      PRISMA and PRISMA-NMA reporting checklists were converted into quantitative
      scores (maximum values of 27 and 32 points). To normalize the values between
      these two checklists, a third score (PRISMA-SCORE) of 0-1 was created. The
      correlation of the scores with NMA publication year, journal impact factor and
      most productive countries were calculated using non-parametric tests. Results: We
      identified 477 NMAs. Only 36.1% of studies reported having followed PRISMA
      statements. The medians of R-AMSTAR, PRISMA and PRISMA-NMA scores were 28 (IQR 25
      31), 21 (IQR 19-23) and 23 (IQR 19-26), respectively. Several problems were noted
      in NMAs (e.g. lack of study protocol, issues in literature searches, lack of raw
      data). NMAs from the most productive countries (USA and China) have similar
      methodological quality. Correlation analyses between R-AMSTAR and normalized
      PRISMA-SCORE revealed a strong positive correlation (Spearman's rho = 0.776; P
      <0.001). A weak but positive correlation was found for PRISMA-SCORE and journal
      impact factor (0.193; P <0.001). Conclusions: The important growth of NMA
      publication rate during the past 5 years is not associated with better
      methodological and reporting quality. Editors, peer reviewers, researchers and
      funding agencies should ensure that methodological and reporting standards are
      met before publication.

PMID- 30212869
TI  - Herpes Simplex Virus-1 qPCR in the Diagnosis of Lower Respiratory Tract
      Infections in Organ Transplant Recipients and Critically Ill Patients.
AB  - Objectives: To determine a quantitative herpes simplex virus (HSV) DNA threshold
      in lower respiratory tract specimens that correlates with positive viral culture
      and clinical outcomes. Methods: Bronchoalveolar lavage and bronchial wash samples
      from 53 HSV culture-positive and 61 culture-negative matched controls were tested
      using HSV-1 and HSV-2 quantitative polymerase chain reaction (qPCR). Results:
      Median viral culture turnaround time was 21.8 days and 9.9 days for culture
      negative and culture-positive specimens, respectively. Using an HSV-1 viral load
      threshold of 1.62 * 103 copies/mL, there was 93% agreement with viral culture. An
      HSV-1 viral load >=1.3 * 104 copies/mL was associated with worse clinical outcome
      compared to a viral load <1.3 * 104 copies/mL (hazard ratio [HR] = 4.27, P =
      .017), and there was a trend of worse outcome compared to patients with
      undetectable HSV-1 DNA (HR = 1.60, P = .056). Conclusions: qPCR has clinical
      utility for rapid accurate identification of HSV-1 in lower respiratory tract
      specimens.

PMID- 30212870
TI  - Capacity assessment in public health community interventions: a systematic
      review.
AB  - The importance of building capacity in community interventions is well
      recognized. There is general agreement about the determinants of capacity and a
      range of existing capacity frameworks, however there is limited evidence or
      consistency in practice around assessing capacity in community interventions. The
      aim of this review was to describe how capacity is assessed in community
      interventions. A systematic review of the literature across four databases
      (MEDLINE, CINAHL, PsycINFO and Sociological Abstracts) was performed. Studies in
      English from 2000 to 2017, that explicitly described how capacity building
      processes were assessed in community interventions in healthy populations, were
      included. All types of empirical study designs were eligible. From 2596 records,
      after exclusion criteria were applied, 19 studies were included describing 12
      different capacity assessment frameworks or tools. Seventeen studies assessed
      capacity processes by measuring individual capacity domains in community
      interventions. The most common capacity domains used to assess capacity were
      leadership, resources, partnerships and intelligence. The majority (n = 15) of
      studies used qualitative or mixed methods designs to measure capacity. Nine
      studies assessed capacity prospectively over time; three before/after and six
      multiple times during the intervention. Five studies assessed capacity
      retrospectively. The findings suggest that capacity assessment may need to remain
      context specific and flexible in order to capture the ever-changing nature of
      capacity building over time. Future research should explore the utility of
      theoretical adaptive capacity assessment guidelines that direct researchers and
      practitioners when describing capacity assessment in community interventions.

PMID- 30212871
TI  - Phenotypic Characterization of Very Early-Onset Inflammatory Bowel Disease with
      Interleukin-10 Signaling Deficiency: Based on a Large Cohort Study.
AB  - Background: Interleukin-10 (IL10)/interleukin-10 receptor (IL10R) deficiency is a
      rare disease with life-threatening infantile-onset colitis. We sought to
      accurately phenotype this disorder based on a large cohort of patients with a
      proven defect of IL10 signaling and to clarify the effects of allogeneic
      hematopoietic stem cell transplantation (HSCT). Methods: We analyzed the
      phenotypes of our 61 patients and reviewed 78 other previously reported cases
      with identified mutations in the genes encoding IL10 or IL10R. We also compared
      the clinical features of patients with interleukin-10 receptor B (IL10RB),
      interleukin-10 receptor A (IL10RA), and IL10 mutations. The therapeutic effects
      of allogeneic HSCT were evaluated. Results: We found that the disease onset time
      was extremely early: 70.3% within 30 days postnatal and 94.9% within the first 6
      months of life. In addition, 94.2% of patients typically presented with perianal
      lesions. Oral ulcers and skin rash were common extra-intestinal manifestations
      (33.8% and 51.8%, respectively). There was no statistically significant
      difference in disease onset time, perianal lesion involvement, or mortality rate
      among patients with IL10RB, IL10RA, or IL10 deficiency. However, the surgery rate
      was higher in patients with IL10RB mutations than in those with IL10 or IL10RA
      mutations (P < 0.05). Compared with those with IL10RA deficiency, a higher
      percentage (32%, 9 of 28) of patients with IL10RB mutations developed B-cell
      lymphoma (P < 0.01). Compared with other regions, a higher percentage (98.7%) of
      IL10RA mutations was detected among patients in East Asia countries (P < 0.01),
      with hot-spot mutation sites of c.C301T and c.G537A. Allogeneic HSCT is
      efficacious but has a high mortality rate (17.5%, 7 of 40). Conclusions: Our
      study expands the current knowledge on the genotype-correlated phenotypes with a
      defect of IL10 signaling. B-cell lymphoma was more frequent than would be
      expected in patients with IL10RB mutations. There may be a unique genetic
      architecture among Eastern Asia compared with other populations. Although
      allogeneic HSCT represents a causal therapeutic approach for IL10-and IL10R
      deficient patients, a word of caution is warranted.

PMID- 30212872
TI  - Using the EPIDEM Model of Quality Improvement to Increase Value of BCR-ABL1
      Tests.
AB  - Objectives: As pathologists and laboratorians, we can enhance patient care by
      promoting the appropriate ordering of diagnostic tests. Our goal was to improve
      the ordering of BCR-ABL1 tests by using the EPIDEM model of quality improvement.
      Methods: We applied the EPIDEM model, which emphasizes understanding local
      context, culture, and resources, to explore inappropriate BCR-ABL1 ordering,
      promote and implement a new reflexive testing strategy in-house, document and
      evaluate effectiveness, and make stepwise modifications. Results: Multiple
      quality improvement interventions correlated with cost savings and decreased
      total errors and incorrect orders for both BCR-ABL1 major and minor positive
      patients. Furthermore, our laboratory built stronger collaborative relationships
      with colleagues within and outside of pathology. Conclusions: Our molecular
      pathology laboratory successfully used the EPIDEM model of quality improvement to
      improve the ordering of BCR-ABL1 tests and promote better patient care by
      focusing on educational efforts and modification of laboratory workflow.

PMID- 30212873
TI  - NK-Cell Enteropathy and Similar Indolent Lymphoproliferative Disorders: A Case
      Series With Literature Review.
AB  - Objectives: We report four new cases of natural killer-cell enteropathy (NKCE)
      and similar lymphoproliferative disorders (LPDs), as well as review the
      literature concerning indolent natural killer (NK)-cell LPDs of the
      gastrointestinal tract. Methods: Pathologic and clinical data were obtained from
      institutional/referral records. Results: Patient 1 (45-year-old man) had anemia;
      a small intestinal lesion was endoscopically biopsied. Patient 2 (65-year-old
      woman) had biliary colic, treated with cholecystectomy. Patient 3 (62-year-old
      man) had a small colonic polyp, biopsied on routine colonoscopy. Patient 4 (68
      year-old man) had presumed Crohn disease; multiple biopsies were performed over
      more than 10 years. Diagnostic specimens showed atypical infiltrates of Epstein
      Barr virus-negative lymphocytes with immunophenotypes suggestive of NK cells. In
      all cases, there was distortion of glandular architecture but no marked
      intraepithelial lymphocytosis or necrosis. The patients did not receive therapy
      for lymphoma and were well on follow-up. Conclusions: These cases support the
      indolent nature of NKCE and similar LPDs, and they indicate that involvement
      outside the alimentary canal may occur.

PMID- 30212874
TI  - Perioperative outcomes of thoracoscopic lung resection requiring a long operative
      time.
AB  - OBJECTIVES: Difficult thoracoscopic surgery sometimes requires a long operative
      time. It is unclear whether patients benefit from such thoracoscopic surgeries.
      We investigated whether thoracoscopic surgery for difficult cases contributed to
      improvements in perioperative outcomes. METHODS: We retrospectively reviewed
      cases of anatomical lung resection with thoracoscopic surgery, including
      conversion to thoracotomy, between January 2006 and December 2016 and compared
      patient demographics and perioperative outcomes of the long (>=360 min) and the
      normal operative time groups (<360 min). RESULTS: One hundred and seventy-six
      patients were in the long operative time group and 655 patients were in the
      normal operative time group. The long operative time group had more male
      patients, more progressive clinical stages, bilobectomy or pneumonectomy,
      conversion to thoracotomy and more blood loss than the normal operative time
      group. The long operative time group had higher rates of postoperative
      complications and longer hospital stay (30% vs 16%, P < 0.001 and 9 +/- 9 days vs
      7 +/- 8 days, P < 0.001; respectively). Multivariate analysis showed that in the
      first half of the operative period, chronic obstructive pulmonary disease and
      bilobectomy or pneumonectomy were independent predictive factors for
      postoperative complications. The long operative time as a factor was close to
      statistical significance (odds ratio 1.689, P = 0.079) unlike the elective
      conversion to thoracotomy (odds ratio 0.784, P = 0.667) and emergency conversion
      to thoracotomy (odds ratio 0.938, P = 0.924). CONCLUSIONS: In conclusion, when
      difficult cases are encountered, conversion to thoracotomy should be considered
      by surgeons if continuation of thoracoscopic surgery increases the operative
      time.

PMID- 30212875
TI  - Precision public health-the Emperor's new clothes.

PMID- 30212876
TI  - Novel lytic bacteriophages of Klebsiella oxytoca ABG-IAUF-1 as the potential
      agents for mastitis phage therapy.
AB  - Mastitis is an inflammation of the mammary gland that occurs when pathogenic
      microorganisms enter the udder. Even though tremendous advancements in veterinary
      diagnosis and therapeutics, mastitis is still the most frequent and costly
      disease of dairy herds overall the world. The purpose of this research was to
      isolate and identify the lytic phages as a potential method for biological
      control of bovine mastitis. In this study Klebsiella oxytoca was isolated from
      contaminated milk samples of Isfahan dairy herds, Isfahan, Iran and characterized
      as K. oxytoca ABG-IAUF-1 and its 16s-rRNA sequence was deposited in GenBank under
      the accession numbers of MF175803.1. Then, the four novel specific lytic
      bacteriophages of K. oxytoca ABG-IAUF-1 from Isfahan public wastewater were
      isolated and identified. The results of transmission electron microscopy
      indicated that theses isolated phages were related to Myoviridae and Podoviridae
      families of bacteriophages. Also the analysis of the growth curve of K. oxytoca
      ABG-IAUF-1 before and after treatment with lytic phage showed the 97% success
      rate of the phages in preventing of bacterial growth. This is the first report
      indicating the use of bacteriophages as the potential agents for eliminating the
      pathogenic bacteria responsible for bovine mastitis in Iran. The applications of
      these lytic phages could be an asset for biocontrolling of pathogenic agents in
      medical and veterinary biotechnology.

PMID- 30212877
TI  - Is there an effect of antithrombotics on carotid intraplaque haemorrhage?

PMID- 30212878
TI  - Dissociable effects of self-reported daily sleep duration on high-level cognitive
      abilities.
AB  - Most people will at some point experience not getting enough sleep over a period
      of days, weeks, or months. However, the effects of this kind of everyday sleep
      restriction on high-level cognitive abilities - such as the ability to store and
      recall information in memory, solve problems, and communicate - remain poorly
      understood. In a global sample of over 10,000 people, we demonstrated that
      cognitive performance, measured using a set of 12 well-established tests, is
      impaired in people who reported typically sleeping less, or more, than 7-8 hours
      per night - which was roughly half the sample. Crucially, performance was not
      impaired evenly across all cognitive domains. Typical sleep duration had no
      bearing on short-term memory performance, unlike reasoning and verbal skills,
      which were impaired by too little, or too much, sleep. In terms of overall
      cognition, a self-reported typical sleep duration of 4 hours per night was
      equivalent to aging 8 years. Also, sleeping more than usual the night before
      testing (closer to the optimal amount) was associated with better performance,
      suggesting that a single night's sleep can benefit cognition. The relationship
      between sleep and cognition was invariant with respect to age, suggesting that
      the optimal amount sleep is similar for all adult age groups, and that sleep
      related impairments in cognition affect all ages equally. These findings have
      significant real-world implications, because many people, including those in
      positions of responsibility, operate on very little sleep and may suffer from
      impaired reasoning, problem-solving, and communications skills on a daily basis.

PMID- 30212879
TI  - Health and Safety Education in Auto Body Collision and Machine Tool Technology
      Programs in Vocational Colleges: Challenges and Opportunities.
AB  - Collision repair, machining, and metal manufacturing are industries with a large
      percentage of small businesses whose owners face unique challenges implementing
      health and safety regulatory requirements. Previous research found that 72% of
      collision repair technicians and 47% of machinists attended some classes or
      graduated from vocational colleges. Although health and safety is a mandatory
      part of the curricula for post-secondary vocational education, little is known
      about what, how, and when health and safety is taught and if teaching is
      effective. Surveys and discussion groups were used to evaluate health and safety
      education in two vocational colleges in Minnesota. Six instructors and 76
      students in collision repair, and 6 instructors and 130 students in machine tool
      technology programs participated. Instructors had no formal training in health
      and safety, few teaching materials, and lacked opportunities to learn about
      safety in their trade. Teaching was unscripted and heavily influenced by each
      instructor'sTM industry experience, knowledge, perceptions and attitude towards
      safety, with little or no guidance from school administration, or safety
      professionals. Student survey results show that graduates have significant gaps
      in safety and health knowledge. Standardized trade-specific curricula and
      instructor training are needed to ensure students receive adequate health and
      safety education.

PMID- 30212880
TI  - Safety Talk and Safety Culture: Discursive Repertoires as Indicators of Workplace
      Safety and Health Practice and Readiness to Change.
AB  - Background: Small construction businesses (SCBs) account for a disproportionate
      share of occupational injuries, days lost, and fatalities in the US and other
      modern economies. Owner/managers of SCBs confront risks associated with their own
      and workers' safety and business survival, and their occupational safety and
      health (OSH) related values and practices are key drivers of safety and business
      outcomes. Given owner/mangers are the key to understanding and affecting change
      in smaller firms, as well as the pressing need for improved OSH in small firms
      particularly in construction, there is a critical need to better understand SCB
      owners' readiness to improve or adopt enhanced OSH activities in their business.
      Unfortunately, the social expectation to support safety can complicate efforts to
      evaluate owners' readiness. Objectives: To get a more accurate understanding of
      the OSH values and practices of SCBs and the factors shaping SCB owners'
      readiness and intent to implement or improve safety and health programming by
      comparing their discourse on safety with their self-rated level of stage of
      change. Methods: In-depth, semi-structured interviews were conducted with 30 SCB
      owner managers. Respondents were asked to self-rate their safety program activity
      on a 5-point scale from unaware or ignorant ('haven't thought about it at all')
      to actively vigilant ('well-functioning safety and health program for at least 6
      months'). They were also asked to discuss the role and meaning of OSH within
      their trade and company, as well as attitudes and inclinations toward improving
      or enhancing business safety practices. Analysis and results: Respondents' self
      rating of safety program activity was compared and contrasted with results from
      discourse analysis of their safety talk, or verbal descriptions of their safety
      values and activities. Borrowing from normative and stage theories of safety
      culture and behavioral change, these sometimes contradictory descriptions were
      taxonomized along a safety culture continuum and a range of safety cultures and
      stages of readiness for change were found. These included descriptions of strong
      safety cultures with intentions for improvement as well as descriptions of safety
      cultures with more reactive and pathological approaches to OSH, with indications
      of no intentions for improvement. Some owner/managers rated themselves as having
      an effective OSH program in place, yet described a dearth of OSH activity and/or
      value for OSH in their business. Conclusion: Assessing readiness to change is key
      to improving OSH performance, and more work is needed to effectively assess SCB
      OSH readiness and thus enable greater adoption of best practices.

PMID- 30212881
TI  - Components of an Occupational Safety and Health Communication Research Strategy
      for Small- and Medium-Sized Enterprises.
AB  - The majority of the global labor force works in firms with fewer than 50
      employees; firms with fewer than 250 employees make up 99% of workplaces. Even
      so, the lack of extensive or comprehensive research has failed to focus on
      occupational safety and health communication to these small- and medium-sized
      enterprises (SMEs). Given that the magnitude of all occupational safety and
      health (OSH) morbidity, mortality, and injury disproportionately occurs in
      businesses with fewer than 250 employees, efforts to communicate with employers
      to engage in preventative occupational safety and health efforts merit attention.
      This article provides an overview of important components that should be
      considered in developing an occupational safety and health (OSH) communication
      research strategy targeting SMEs. Such a strategy should raise awareness about
      the diversity and complexity of SMEs and the challenges of targeting OSH
      communication toward this diverse group. Companies of differing sizes (e.g. 5,
      50, 500 employees) likely require differing communication approaches.
      Communication strategies will benefit from deconstructing the term 'small
      business' into smaller, more homogenous categories that might require approaches.
      Theory-based research assessing barriers, message content, channels, reach,
      reception, motivation, and intention to act serve as the foundation for
      developing a comprehensive research framework. Attention to this type of research
      by investigators is warranted and should be encouraged and supported. There would
      also be value in developing national and international strategies for research on
      communication with small businesses.

PMID- 30212882
TI  - Conference Summary Understanding Small Enterprises Conference, 25-27 October
      2017.
AB  - Objectives: The specific objectives of the 2017 Understanding Small Enterprises
      Conference were to: (i) identify successful strategies for overcoming
      occupational safety and health (OS&H) barriers in small and medium-sized
      enterprises (SMEs); (ii) disseminate best practices to research and business
      communities; (iii) build collaborations between different stakeholders including
      researchers, insurers, small enterprises, government agencies; and (iv) better
      inform OS&H research relevant to SMEs. Methods: A two and a half day
      international conference was organized, building upon three previously successful
      iterations. This conference brought together researchers, practitioners, and
      other stakeholders from 16 countries to share best practices and emerging
      strategies for improving OS&H in SMEs. Findings: Cross-cutting themes that
      emerged at the conference centered around: 1) stakeholder and intermediary
      involvement; 2) what occupational health and safety looks like across different
      industries; 3) intervention programs (tools and resources); 4) precarious and
      vulnerable work and the informal sector; and 5) Total Worker Health(r) in SMEs.
      Conclusion: A number of innovative initiatives were shared at the conference.
      Researchers must build collaborations involving a variety of stakeholder groups
      to ensure that OS&H solutions are successful in SMEs. Future OS&H research should
      continue to build upon the successful work of the 2017 Understanding Small
      Enterprises Conference.

PMID- 30212883
TI  - Developing an Integrated Approach to Workplace Mental Health: A Hypothetical
      Conversation with a Small Business Owner.
AB  - An integrated approach to workplace mental health encompasses three main areas of
      activity: (i) protecting mental health by reducing work-related and other risk
      factors for mental health problems, (ii) promoting mental health by developing
      the positive aspects of work as well as worker strengths and positive capacities,
      and (iii) responding to mental health problems as they manifest at work
      regardless of cause (work-related or otherwise). This represents an effort to
      distil what is a complex issue warranting a correspondingly complex set of
      responses into information for action that is accessible and engaging to
      workplace stakeholders, and that enables workplaces to begin from varying
      starting points to build over time towards mature multicomponent workplace mental
      health programs. This article, based on a plenary presentation at the
      Understanding Small Enterprises 2017 international conference (25-27 October
      2017, Denver), is presented in two parts. Part I is a concise summary of our
      integrated approach to workplace mental health. Part II presents a hypothetical
      conversation with a small business owner/operator who has yet to implement
      workplace mental health programs, but is considering doing so. In this
      Conversation, representing an effort in knowledge translation, we attempt to
      convince the small business owner/operator to begin taking action.

PMID- 30212884
TI  - The Impact of Worksite Wellness Programs by Size of Business: A 3-Year
      Longitudinal Study of Participation, Health Benefits, Absenteeism, and
      Presenteeism.
AB  - Objective: Worksite wellness programs (WWP) may positively impact employee
      health, medical expenditures, absenteeism, and presenteeism. However, there has
      been little research to assess the benefits of WWP in small businesses. The
      purpose of this study is to prospectively evaluate changes in health,
      absenteeism, and presenteeism for employees who participated in a WWP. Methods:
      We conducted an observational, 3-year cohort study of 5766 employees from 314
      businesses of differing sizes. We followed two cohorts of employees, who
      completed at least two annual health risk assessments (HRA) between May 2010 and
      December 2014. Changes from baseline to the first and second follow-up periods
      were assessed for chronic and non-chronic health conditions, absenteeism, and
      presenteeism. Results: Small business employees were more likely to participate
      in the WWP than were employees from large businesses. Changes in chronic and non
      chronic health conditions varied by size of business, with small business
      employees showing improvements in stress, overall health, depression, smoking
      status, vegetable and fruit consumption, and physical activity, and in their
      perceptions of job health culture. In contrast, large business employees
      experienced improvements in stress, vegetable consumption, and alcohol use. No
      changes in absenteeism or presenteeism were observed. Conclusions: Small
      businesses achieve higher employee participation rates and more health
      improvements when compared to employees from large employers. Findings suggest
      that small businesses may gain the most from a WWP.

PMID- 30212885
TI  - Engaging Small Residential Construction Contractors in Community-Based
      Participatory Research to Promote Safety.
AB  - Construction is a large employment sector with a high prevalence of small
      businesses. Despite the high injury rates reported for employees of small
      construction firms, these firms are under-represented in occupational safety
      research studies. Such studies are needed to understand barriers experienced by
      these firms and to examine ways to overcome them. However, challenges accessing
      and recruiting this hard-to-reach population are frequently reported. Traditional
      approaches of recruiting through unions or workers' compensation insurers may not
      be appropriate or effective for small construction businesses. Previous studies
      have demonstrated the value of academic collaborations with community-based
      organizations for recruiting participants from hard-to-reach populations for
      research studies. In accordance with the principles of Community-Based
      Participatory Research (CBPR), we formed a recruitment team comprised of staff
      from a local union, a community organization, and a community outreach team to
      recruit small construction contractors in Lawrence, MA. Media marketing
      strategies, participation in community events, exploring neighborhoods in search
      of ongoing residential projects, and partnership with vocational training
      institutions and building trade associations were some of the strategies
      implemented during this project. We recruited 118 contractors, supervisors, and
      foremen from more than 50 construction firms across the Greater Lawrence area to
      participate in an intervention project to reduce falls and silica exposure. The
      CBPR approach facilitated the development and implementation of recruitment
      strategies that resulted in the participation of a significant number of hard-to
      reach small construction contractors.

PMID- 30212886
TI  - Intermediaries Supporting Occupational Health and Safety Improvements in Small
      Businesses: Development of Typology and Discussion of Consequences for Preventive
      Strategies.
AB  - Intermediaries have been suggested as a potential source for improving
      Occupational Health and Safety (OHS) in small businesses (SBs), because SB due to
      their sheer number and limited managerial and financial resources typically have
      weak OHS management and higher occupational risks. SB furthermore typically has a
      reactive approach to OHS and do not seek out OHS assistance on their own. We
      propose, based on a large comparative study of SB and intermediaries, a general
      typology for intermediaries in relation to SB, and further, discuss the
      implications for preventive strategies in SB. We argue that there is a strong
      potential for improving OHS by including various intermediaries, however, the
      inclusion is not enough in itself. The interests of the intermediaries and the
      OHS improvement must be aligned, and the efforts across various intermediaries
      should be orchestrated among the key actors to maximize the outcome.

PMID- 30212887
TI  - What Could Total Worker Health(r) Look Like in Small Enterprises?
AB  - Small enterprises have fewer resources, are more financially precarious, and have
      higher rates of occupational injury and illness compared with larger enterprises.
      Interventions that address the promotion of health and well-being in addition to
      traditional occupational safety and health hazards, a Total Worker Health(r)
      (TWH) approach, may be effective in reducing injuries and preventing illness.
      However, little research has examined the impact of TWH interventions in small
      enterprises. The aim of this research was to explore and characterize health and
      safety practices, policies, and programs in small Midwestern enterprises from a
      TWH perspective. Utilizing a case studies approach, site visits were conducted
      with small business, between 10 and 250 employees, from 2014 through 2016 and
      included workplace audits and interviews with multiple employees in varying roles
      within each organization. Both open and closed coding were used to identify
      specific themes. Eight themes emerged from the site visits: value and return on
      investment, organizational factors, program design, engaging employees, low-cost
      strategies, evaluation, and integration. These themes overlapped with both the
      National Institute for Occupational Safety and Health's (NIOSH) Essential
      Elements of TWH and the NIOSH Fundamentals. Industry sector and enterprise size
      also affect resources and integration of these resources. As TWH expands to
      organizations of all sizes, it is necessary to address the unique needs of
      smaller enterprises.

PMID- 30212888
TI  - Construction Safety and Health in the USA: Lessons From a Decade of Turmoil.
AB  - The construction industry is one of the largest and also most hazardous
      industries in the USA. It is affected more severely by the business cycle than
      most other industries. We examined industry trends during the last decade
      including the severe recession. During 2008 to 2010, as a result of the
      recession, 2.7 million workers and 20% of all employers left the industry. By
      2010, the number and rate of traumatic fatalities had reached its lowest point
      ever, only to gradually increase again as the industry recovered from the
      recession. The risks of a fatality were disproportionate with employer size. The
      small employers (<20 employees), which account for 37.5% of employment, were
      responsible for 57% of all fatalities. These small employers are less likely to
      embrace essential safety culture practices and are slow to adopt new approaches
      to occupational safety and health. These employers-especially those which hire
      immigrant workers and self-employed workers-lag far behind in terms of adopting
      even essential elements of good safety cultures and management practices.
      Currently, there are no restrictions on going into business as a construction
      contractor or seeking employment as a construction worker. There is a great need
      to find ways to establish minimum qualifications for becoming a construction
      contractor and for becoming a construction worker. Some jurisdictions have
      established minimum occupational safety and health training. This is a good
      start, but qualifications must include greater emphasis on minimum skills
      requirements. State and local jurisdictions have good policy tools which could be
      deployed for this purpose but which have largely been neglected: licensing of
      both companies and workers could include skills qualifications; construction
      permits could include requirements for occupational safety and health; and
      greater use of criminal prosecution could be pursued where it is obvious that
      basic requirements for safety and health have been ignored.

PMID- 30212889
TI  - Cohort Profile: The Epidemiology of Chronic Diseases Cohort (EpiDoC).

PMID- 30212890
TI  - Arterial hypertension and the turbulent ageing of the aortic valve.

PMID- 30212892
TI  - A geometric morphometric evaluation of hard and soft tissue profile changes in
      borderline extraction versus non-extraction patients.
AB  - Objectives: To evaluate the hard tissue and facial profile changes in matched
      extraction and non-extraction Class I patients by the use of geometric
      morphometrics. Subjects and Methods: From a parent sample of 542 Class I
      patients, previously subjected to discriminant analysis, a subsample of 68
      borderline cases was obtained, 34 treated with extraction and 34 without
      extraction of 4 first premolars. Geometric morphometric methods (Procrustes
      superimposition and Principal Component Analysis) were applied on cephalometric
      tracings to assess the validity of the discriminant analysis in successfully
      identifying a morphologically homogeneous group and to evaluate inter- and intra
      group skeletal and facial profile shape changes. Results: No significant pre
      treatment shape difference between the two groups was found, thus validating the
      discriminant analysis. The non-extraction group showed increase in hard tissue
      facial height (P < 0.001), with slight lower lip retrusion and upper lip
      protrusion (P = 0.027). The extraction group showed retraction of the hard tissue
      and facial profile outline (P < 0.001). Permutation tests for post-treatment
      inter-group differences resulted in P = 0.054 for the soft tissue outline and P =
      0.078 for the hard tissue skeletal component. Conclusions: The evidence indicates
      that borderline cases treated with four premolar extractions will exhibit lip
      retrusion compared to non-extraction treatment.

PMID- 30212891
TI  - Elevated blood pressure and risk of aortic valve disease: a cohort analysis of
      5.4 million UK adults.
AB  - Aims: To test two related hypotheses that elevated blood pressure (BP) is a risk
      factor for aortic valve stenosis (AS) or regurgitation (AR). Methods and results:
      In this cohort study of 5.4 million UK patients with no known cardiovascular
      disease or aortic valve disease at baseline, we investigated the relationship
      between BP and risk of incident AS and AR using multivariable-adjusted Cox
      regression models. Over a median follow-up of 9.2 years, 20 680 patients (0.38%)
      were diagnosed with AS and 6440 (0.12%) patients with AR. Systolic BP (SBP) was
      continuously related to the risk of AS and AR with no evidence of a nadir down to
      115 mmHg. Each 20 mmHg increment in SBP was associated with a 41% higher risk of
      AS (hazard ratio 1.41, 95% confidence interval 1.38-1.45) and a 38% higher risk
      of AR (1.38, 1.31-1.45). Associations were stronger in younger patients but with
      no strong evidence for interaction by gender or body mass index. Each 10 mmHg
      increment in diastolic BP was associated with a 24% higher risk of AS (1.24, 1.19
      1.29) but not AR (1.04, 0.97-1.11). Each 15 mmHg increment in pulse pressure was
      associated with a 46% greater risk of AS (1.46, 1.42-1.50) and a 53% higher risk
      of AR (1.53, 1.45-1.62). Conclusion: Long-term exposure to elevated BP across its
      whole spectrum was associated with increased risk of AS and AR. The possible
      causal nature of the observed associations warrants further investigation.

PMID- 30212893
TI  - Tomographic regression of pulmonary rheumatoid nodules under baricitinib therapy.

PMID- 30212894
TI  - Distinctive structural basis for DNA recognition by the fission yeast Zn2Cys6
      transcription factor Pho7 and its role in phosphate homeostasis.
AB  - Pho7, a member of the Zn2Cys6 family of fungal transcription factors, is the key
      transcriptional activator underlying fission yeast phosphate homeostasis, a
      physiological response to phosphate starvation in which the pho1, pho84 and tgp1
      genes are upregulated. Here, we delineated a minimized 61-amino-acid Pho7 DNA
      binding domain (DBD) and determined the 1.7 A crystal structure of the DBD at its
      target site in the tgp1 promoter. Two distinctive features of the Pho7 DBD are:
      it binds DNA as a monomer, unlike most other fungal zinc-cluster factors that
      bind as homodimers; and it makes extensive interactions with its asymmetric
      target sequence over a 14-bp footprint that entails hydrogen bonding to 13
      individual bases within, and remote from, the CGG triplet typically recognized by
      other Zn2Cys6 DBDs. Base pair substitutions at Pho7 sites in the tgp1 and pho1
      promoters highlight the importance of the 5'-CGG triplet for Pho7 binding in
      vitro and Pho7-dependent gene expression in vivo. We identify several DBD amino
      acids at which alanine substitution effaced or attenuated the pho1 phosphate
      starvation response and concordantly reduced Pho7 binding to a pho1 promoter
      site.

PMID- 30212895
TI  - Admissions for ambulatory care sensitive conditions: a national observational
      study in the general and COPD population.
AB  - Background: Hospital admissions for ambulatory care sensitive conditions (ACSCs)
      may be prevented by effective ambulatory management and treatment. ACSC
      admissions is used as indicator for primary care quality and accessibility.
      However, debate continues to which extent these admissions are truly preventable.
      The aim of this study was to provide more objective insight into the
      preventability of ACSC admissions. Methods: Observational study using 2012-15
      health insurer claim data of 13 182 602 Dutch insured inhabitants. Logistic
      multilevel regression analyses were conducted to investigate factors (ambulatory
      care and characteristics of inhabitants) possibly associated with ACSC
      admissions. Prior ambulatory care use was examined for patients with an ACSC
      contributing to the highest number of ACSC admissions: chronic obstructive
      pulmonary disease (COPD). Results: In 2014, 89.8 hospital admissions for ACSCs
      per 10 000 insured inhabitants were claimed. Percentage of inhabitants with ACSC
      admissions varied between general practices from 0.58-0.84%. ASCS admissions were
      hardly associated with ambulatory care. One month prior to admission, 97% of
      admitted COPD patients had at least one ambulatory care contact. Conclusions:
      Variation in ACSC admissions between general practitioners was observed,
      indicating that certain hospital admissions may be prevented. However, we found
      no indication that ACSC admissions were preventable, as no link was found with
      the provision of ambulatory care and ACSC admissions. This may indicate that this
      indicator is country and health care system specific. Before including ACSC
      admission as quality indicator of primary care in the Netherlands, more insight
      into the causes of variation is required.

PMID- 30212896
TI  - Learning from other autoimmunities to understand targeting of B cells to control
      multiple sclerosis.
AB  - Although many suspected autoimmune diseases are thought to be T cell-mediated,
      the response to therapy indicates that depletion of B cells consistently inhibits
      disease activity. In multiple sclerosis, it appears that disease suppression is
      associated with the long-term reduction of memory B cells, which serves as a
      biomarker for disease activity in many other CD20+ B cell depletion-sensitive,
      autoimmune diseases. Following B cell depletion, the rapid repopulation by
      transitional (immature) and naive (mature) B cells from the bone marrow masks the
      marked depletion and slow repopulation of lymphoid tissue-derived, memory B
      cells. This can provide long-term protection from a short treatment cycle. It
      seems that memory B cells, possibly via T cell stimulation, drive relapsing
      disease. However, their sequestration in ectopic follicles and the chronic
      activity of B cells and plasma cells in the central nervous system may drive
      progressive neurodegeneration directly via antigen-specific mechanisms or
      indirectly via glial-dependent mechanisms. While unproven, Epstein-Barr virus may
      be an aetiological trigger of multiple sclerosis. This infects mature B cells,
      drives the production of memory B cells and possibly provides co-stimulatory
      signals promoting T cell-independent activation that breaks immune tolerance to
      generate autoreactivity. Thus, a memory B cell centric mechanism can integrate:
      potential aetiology, genetics, pathology and response to therapy in multiple
      sclerosis and other autoimmune conditions with ectopic B cell activation that are
      responsive to memory B cell-depleting strategies.

PMID- 30212897
TI  - Arbuscular mycorrhizal fungal communities and global change: an uncertain future.
AB  - Arbuscular mycorrhizal (AM) fungi are amongst the most common and functionally
      important symbionts of terrestrial plants and are highly likely to be affected by
      global change. The potential consequences of this on plant growth and carbon and
      nutrient cycling has led to a growing demand for their inclusion in global change
      models. However, our understanding of their responses to environmental change
      remains limited. This review provides an overview of recent experiments
      attempting to predict the effects of atmospheric and climatic change on AM fungal
      community diversity, composition and functioning. This includes rising
      atmospheric carbon dioxide and tropospheric ozone levels, altered water
      availability, warming and nitrogen deposition. Changes detected are often highly
      variable and context dependent, but trends are emerging such as the similar
      responses of community composition to enhanced nitrogen deposition and
      atmospheric CO2, despite the likely contrasting effects of these environmental
      changes on carbon availability. The review also highlights shortfalls in our
      current knowledge and suggests priorities for future research, particularly
      advocating more integrated approaches linking the study of community
      characteristics and functions and examination of fine level genetic changes,
      wider geographical contexts and a greater range of AM fungal functions.

PMID- 30212898
TI  - Is what you see all there is?

PMID- 30212899
TI  - Experience with stentless biological aortic valves.

PMID- 30212901
TI  - Assessment of the anti-biofilm effect of micafungin in an animal model of
      catheter-related candidemia.
AB  - In cases where catheter-related candidemia (CRC) must be managed without catheter
      withdrawal, antifungal lock therapy using highly active anti-biofilm (HAAB)
      agents is combined with systemic treatment. However, the activity of HAAB agents
      has never been studied in in vivo models using bioluminescence. We assessed the
      efficacy of micafungin using a bioluminescent Candida albicans SKCA23-ACTgLuc
      strain in an animal model of CRC. We divided 33 female Wistar rats into five
      groups: sham (A), infected nontreated (B), treated with lock therapy (0.16 mg/ml)
      (C), systemically treated only (1 mg/kg) (D), and systemically treated+lock (E).
      Catheters were colonized 24 h before insertion into the femoral vein (day 0).
      Treatment started on day 1 and lasted 7 days, followed by 7 days of surveillance.
      Bioluminescence assays were carried out on days 1, 3, 5, and 14, together with
      daily monitoring of clinical variables. Postmortem microbiological cultures from
      the catheter and several tissue samples were also obtained. Overall, 28 rats
      (84.8%) completed the study. Group B animals showed significant weight loss at
      days 2, 4, and 5 compared with groups C and D (P < .05). In group B, no animals
      survived after day 7, 75% had CRC, and bioluminescence remained constant 5 days
      after catheter implantation. Positive catheter culture rates in groups C, D, and
      E were, respectively, 83.3%, 62.5%, and 25.0% (P = .15). Micafungin proved to be
      a HAAB agent when administered both systemically and in lock therapy in an animal
      model of CRC, although the bioluminescence signal persists after treatment. This
      persistence should be further analyzed.

PMID- 30212900
TI  - Synthetic negative feedback circuits using engineered small RNAs.
AB  - Negative feedback is known to enable biological and man-made systems to perform
      reliably in the face of uncertainties and disturbances. To date, synthetic
      biological feedback circuits have primarily relied upon protein-based,
      transcriptional regulation to control circuit output. Small RNAs (sRNAs) are non
      coding RNA molecules that can inhibit translation of target messenger RNAs
      (mRNAs). In this work, we modelled, built and validated two synthetic negative
      feedback circuits that use rationally-designed sRNAs for the first time. The
      first circuit builds upon the well characterised tet-based autorepressor,
      incorporating an externally-inducible sRNA to tune the effective feedback
      strength. This allows more precise fine-tuning of the circuit output in contrast
      to the sigmoidal, steep input-output response of the autorepressor alone. In the
      second circuit, the output is a transcription factor that induces expression of
      an sRNA, which inhibits translation of the mRNA encoding the output, creating
      direct, closed-loop, negative feedback. Analysis of the noise profiles of both
      circuits showed that the use of sRNAs did not result in large increases in noise.
      Stochastic and deterministic modelling of both circuits agreed well with
      experimental data. Finally, simulations using fitted parameters allowed dynamic
      attributes of each circuit such as response time and disturbance rejection to be
      investigated.

PMID- 30212903
TI  - Missed opportunities to identify occupational asthma in acute secondary care.

PMID- 30212904
TI  - Mentoring in occupational medicine: where might it fit in?

PMID- 30212902
TI  - The RNA exosome contributes to gene expression regulation during stem cell
      differentiation.
AB  - Gene expression programs change during cellular transitions. It is well
      established that a network of transcription factors and chromatin modifiers
      regulate RNA levels during embryonic stem cell (ESC) differentiation, but the
      full impact of post-transcriptional processes remains elusive. While cytoplasmic
      RNA turnover mechanisms have been implicated in differentiation, the contribution
      of nuclear RNA decay has not been investigated. Here, we differentiate mouse
      ESCs, depleted for the ribonucleolytic RNA exosome, into embryoid bodies to
      determine to which degree RNA abundance in the two states can be attributed to
      changes in transcription versus RNA decay by the exosome. As a general
      observation, we find that exosome depletion mainly leads to the stabilization of
      RNAs from lowly transcribed loci, including several protein-coding genes.
      Depletion of the nuclear exosome cofactor RBM7 leads to similar effects. In
      particular, transcripts that are differentially expressed between states tend to
      be more exosome sensitive in the state where expression is low. We conclude that
      the RNA exosome contributes to down-regulation of transcripts with disparate
      expression, often in conjunction with transcriptional down-regulation.

PMID- 30212905
TI  - Disaster risk reduction and sustainable development: the role for occupational
      health.

PMID- 30212906
TI  - Reply.

PMID- 30212907
TI  - Suspected endocarditis turns out to be a fibroelastoma.

PMID- 30212908
TI  - Snapshots of archaeal DNA replication and repair in living cells using super
      resolution imaging.
AB  - Using the haloarchaeon Haloferax volcanii as a model, we developed nascent DNA
      labeling and the functional GFP-labeled single-stranded binding protein RPA2 as
      novel tools to gain new insight into DNA replication and repair in live
      haloarchaeal cells. Our quantitative fluorescence microscopy data revealed that
      RPA2 forms distinct replication structures that dynamically responded to
      replication stress and DNA damaging agents. The number of the RPA2 foci per cell
      followed a probabilistic Poisson distribution, implying hitherto unnoticed
      stochastic cell-to-cell variation in haloarchaeal DNA replication and repair
      processes. The size range of haloarchaeal replication structures is very similar
      to those observed earlier in eukaryotic cells. The improved lateral resolution of
      3D-SIM fluorescence microscopy allowed proposing that inhibition of DNA synthesis
      results in localized replication foci clustering and facilitated observation of
      RPA2 complexes brought about by chemical agents creating DNA double-strand
      breaks. Altogether our in vivo observations are compatible with earlier in vitro
      studies on archaeal single-stranded DNA binding proteins. Our work thus
      underlines the great potential of live cell imaging for unraveling the dynamic
      nature of transient molecular interactions that underpin fundamental molecular
      processes in the Third domain of life.

PMID- 30212909
TI  - MetaHCR: a web-enabled metagenome data management system for hydrocarbon
      resources.
AB  - The ever-increasing metagenomic data necessitate appropriate cataloguing in a way
      that facilitates the comparison and better contextualization of the underlying
      investigations. To this extent, information associated with the sequencing data
      as well as the original sample and the environment where it was obtained from is
      crucial. To date, there are not any publicly available repositories able to
      capture environmental metadata pertaining to hydrocarbon-rich environments. As
      such, contextualization and comparative analysis among sequencing datasets
      derived from these environments is to a certain degree hindered or cannot be
      fully evaluated. The metagenomics data management system for hydrocarbon
      resources (MetaHCRs) enables the capturing of marker gene and whole metagenome
      sequencing data as well as over 300 contextual attributes associated with
      samples, organisms, environments and geological properties, among others.
      Moreover, MetaHCR implements the Minimum Information about any Sequence
      hydrocarbon resource specification from the Genomic Standards Consortium; it
      integrates a user-friendly web interface and relational database model, and it
      enables the generation of complex custom search. MetaHCR has been tested with 36
      publicly available metagenomic studies, and its modular architecture can be
      easily customized for other types of environmental and metagenomics studies.

PMID- 30212911
TI  - Hemagglutination ability and hemolytic activity of Trichosporon asahii.
AB  - Trichosporon asahii is a human fungal pathogen that causes deep-seated infections
      in immunocompromised patients. While the pathogenic mechanisms of T. asahii
      remain unknown, our previous studies indicate that adherent colony morphologies
      were generated from parent strains, which may contribute to their pathogenicity.
      In the present study, we analyzed the hemolytic and hemagglutination activities
      of T. asahii. We report that T. asahii cells demonstrate hemagglutination and
      hemolytic activities, and that cell surface molecules play a role in the
      hemagglutination activity of adherent strains. These observations suggest that
      hemagglutination and hemolysis may be one of the pathogenic mechanisms of T.
      asahii.

PMID- 30212910
TI  - Spfy: an integrated graph database for real-time prediction of bacterial
      phenotypes and downstream comparative analyses.
AB  - Public health laboratories are currently moving to whole-genome sequence (WGS)
      based analyses, and require the rapid prediction of standard reference laboratory
      methods based solely on genomic data. Currently, these predictive genomics tasks
      rely on workflows that chain together multiple programs for the requisite
      analyses. While useful, these systems do not store the analyses in a genome
      centric way, meaning the same analyses are often re-computed for the same
      genomes. To solve this problem, we created Spfy, a platform that rapidly performs
      the common reference laboratory tests, uses a graph database to store and
      retrieve the results from the computational workflows and links data to
      individual genomes using standardized ontologies. The Spfy platform facilitates
      rapid phenotype identification, as well as the efficient storage and downstream
      comparative analysis of tens of thousands of genome sequences. Though generally
      applicable to bacterial genome sequences, Spfy currently contains 10 243
      Escherichia coli genomes, for which in-silico serotype and Shiga-toxin subtype,
      as well as the presence of known virulence factors and antimicrobial resistance
      determinants have been computed. Additionally, the presence/absence of the entire
      E. coli pan-genome was computed and linked to each genome. Owing to its database
      of diverse pre-computed results, and the ability to easily incorporate user data,
      Spfy facilitates hypothesis testing in fields ranging from population genomics to
      epidemiology, while mitigating the re-computation of analyses. The graph approach
      of Spfy is flexible, and can accommodate new analysis software modules as they
      are developed, easily linking new results to those already stored. Spfy provides
      a database and analyses approach for E. coli that is able to match the rapid
      accumulation of WGS data in public databases.

PMID- 30212912
TI  - The Cardioband annuloplasty system: is it ready for prime time?

PMID- 30212913
TI  - Looking up to virtue: averting gaze facilitates moral construals via
      posteromedial activations.
AB  - Witnessing exemplary actions triggers admiration, a positive emotion that can
      pertain to concrete skills, or move the onlooker beyond physical characteristics
      to appreciate the abstract, moral implications. Participants reacted to
      narratives depicting skilled or virtuous protagonists first during a videotaped
      interview then during functional magnetic resonance imaging (fMRI). We analyzed
      participants' gaze aversion (an indicator of disengaging from the immediate
      environment) and cognitive construals (mentions of concrete characteristics vs
      abstract beliefs and values) during the interview, and relations to individuals'
      subsequent neural activations. When participants averted their gaze, they were
      more likely to mention abstract construals, and both behaviors were more likely
      when reacting to virtue. Gaze aversion to virtue narratives predicted greater
      subsequent activation for those narratives in dorsal posterior cingulate cortex
      (dPCC), involved in visual attention control. The inferior-posterior
      posteromedial cortices (ipPMC), a default mode network hub involved in abstract
      thought, activated only to virtue, and activity level reflected individuals'
      tendency to abstract construals. Critically, dPCC and ipPMC activity sequentially
      mediated the relationship between individuals' gaze and abstract construal
      tendencies. No such relationships existed for reactions to skill, despite
      participants reporting equivalently strong positive emotion. In appreciating
      virtue, dPCC may support individuals in transcending the viewable context,
      facilitating ipPMC activity and moral construals.

PMID- 30212914
TI  - [Short Stem, Straight Stem or Anatomical Stem: Free Decision or Recommendations?]
AB  - The main goal of total hip arthroplasty is to reduce pain. But function,
      stability, and longevity are also of major importance. Since the inauguration of
      modern total hip arthroplasty by Charnley, the designs of stems has undergone
      many changes. The following paper concerns the straight stem, the anatomical stem
      and the short stem in total hip arthroplasty. It attempts to answer the question
      as to whether there is a recommendation for the use of a special stem. The
      straight stem is the oldest of these stem types. Depending on the particular
      design, the anchorage of these stems may lie in the metaphyseal or the diaphyseal
      parts of the femur. The closer the contact of the stem is to the diaphyseal part,
      the greater is the risk of stress shielding. The anatomical stem attempts to
      match the geometry of the proximal femoral endosteal. This can be helpful to
      reconstruct the natural load bearing but has also limitations in fitting. The
      short stem was designed to achieve an anatomical pattern of stress distribution,
      resection of less bone and reduction in thigh pain. There are additional
      differences between the designs. But not only the stem design has to be
      considered. The proximal part of the femur exhibits a great variety of
      morphologies. Whereas younger patients mostly have secondary osteoarthritis due
      to deformities, elderly patients may have changes in morphology due e.g.
      osteoporosis. Depending on these patient-specific factors and bearing
      biomechanical aspects in mind, the surgeon must choose the stem design. This may
      require different stem designs with different mechanisms of fixation.

PMID- 30212915
TI  - The Sacred Cow in Orthopaedics.

PMID- 30212916
TI  - Treatment of Long Bone Fractures in Calves with Ilizarov External Fixator.
AB  - In this study, the advantages and disadvantages of Ilizarov external fixator in
      the treatment of long bone fractures in calves were investigated. For this
      purpose, 26 calves of different breeds, ages and genders, having metacarpal (n =
      12), metatarsal (n = 5) and antebrachial (n = 9) fractures underwent surgery
      under general anaesthesia. Frames, which were prepared before surgery in
      accordance with the radiographic findings, were applied under open reduction in
      18 cases, and under closed reduction in eight cases. In the postoperative period,
      all calves except one started to bear some weigh on the injured limb on the first
      day, while the remaining calf did the same on the second day. The consolidation
      started in the first 2 weeks for 24 of the calves and was completed by the day
      55. In the two remaining cases, it started in the third week and was completed on
      day 71 and day 90, respectively.The soft tissue wounds were completely healed in
      all calves and no complications occurred. In five calves that were not kept in
      our clinic pin tract infections formed. They were controlled rapidly, and there
      was no change in the fracture reduction or healing duration.In conclusion, in our
      study, the Ilizarov external fixator system was applied to long bone fractures in
      cattle calves, in cases where the fragments were not large enough to apply pins
      and plates, and which became open and infected after defective bandage practices
      or unsuitable treatment. Fractures completely healed in all cases, without any
      complications. These results show that many of the long bone fractures
      experienced by calves, that were considered for amputation due to the anticipated
      inability to treat them successfully, could be treated with the use of the
      Ilizarov system.

PMID- 30212918
TI  - Early Failure in Medial Unicondylar Arthroplasty: Radiographic Analysis on the
      Importance of Joint Line Restoration.
AB  - Survivorship of unicondylar knee arthroplasty (UKA) remains a drawback,
      especially compared with the outcome of total knee arthroplasty. This could be
      improved by identifying and correcting failure mechanisms. To this purpose, this
      study aimed at exploring failure modalities of UKA, with particular focus on the
      role of joint line (JL) position and alignment as variable to be optimized for a
      successful outcome. This study explored modes of failure in 266 medial UKAs.
      Radiological comparison was performed between 24 failures and 24 matched
      controls, to determine the importance of UKA positioning in terms of femorotibial
      angle (FTA), tibial plateau angle, and posterior tibial slope (PTS). Radiographic
      comparative analysis showed statistically significant differences in the failure
      group compared with the control group in terms of variation in FTA (p = 0.0222),
      PTS (p = 0.0025), and JL height (p = 0.0022). Variations not only in FTA but also
      PTS and JL height were correlated with failures observed in this series. Thus,
      based on the results of this study, it emerges that JL position should be
      carefully controlled in all planes while implanting a UKA. This is a Level III,
      case-control study.

PMID- 30212917
TI  - Implementing Obstetric Venous Thromboembolism Protocols on a Statewide Basis:
      Results from New York State's Safe Motherhood Initiative.
AB  - OBJECTIVE:  To determine whether a state-level initiative to reduce obstetric
      venous thromboembolism (VTE) risk affected outcomes and process measures.
      METHODS:  In 2013, the Safe Motherhood Initiative (SMI) developed a VTE safety
      bundle to reduce obstetric VTE risk. A total of 117 of 124 hospitals providing
      obstetrical services in New York participated in SMI. Data evaluating
      thromboembolism events (deep vein thrombosis and pulmonary embolism) and
      thromboprophylaxis process measures were collected from March through November
      2015. RESULTS:  A total of 107 hospitals, in any individual quarter, reported
      data on each of the VTE bundle outcomes and measures. Centers that provided low
      risk care (Level 1 centers) reported the lowest rate of bundle implementation at
      the end of the study period (55.6%). Mechanical prophylaxis for a cesarean was
      common at all centers. Hospitals that adopted the bundle were more likely to
      provide routine pharmacologic prophylaxis for women undergoing cesarean. The risk
      of VTE did not differ by bundle implementation. CONCLUSION:  While adoption of
      the SMI VTE bundle occurred at a majority of centers across New York, uptake was
      less likely at low-acuity centers. Bundle adoption was associated with
      implementation of recommended practices. The rare nature of VTE events
      underscores the need for large data samples to determine the best prophylaxis
      strategies.

PMID- 30212919
TI  - Outcomes of Anterior Cruciate Ligament Reconstruction in Females Using Patellar
      Tendon-Bone versus Hamstring Autografts: A Systematic Review and Meta-Analysis.
AB  - The current review aims to compare the outcomes of anterior cruciate ligament
      (ACL) reconstruction in the female population after patellar-tendon-bone and
      hamstring grafts. The review was conducted using the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses guidelines. All original randomized
      controlled trials and prospective cohort studies that compared clinical outcomes
      after female ACL reconstruction using hamstring versus patellar-tendon-bone
      grafts were included. All clinical outcomes reported by three or more studies
      were included. Fifteen publications, with 948 female patients, were included.
      Most outcomes were reported to have no significant graft differences by all
      studies that reported the outcome. These included all the outcomes for objective
      knee scores (International Knee Documentation Committee [IKDC] objective knee
      score), neuromuscular testing (quadriceps strength, hamstring strength, and
      single hop test), graft rupture or failure, and subjective knee scores (Lysholm
      score and IKDC subjective knee score). The pivot shift test, flexion deficit, and
      presence of crepitus were also reported to have no significant graft differences
      by all studies. Some studies reported a significant difference in anteroposterior
      laxity (Lachman's test and instrumented laxity), range of motion deficits
      (extension deficit), and sports and activity level (Tegner score). However, these
      statistically significant differences were noted to be clinically insignificant
      due to the normal population variation or standard error of measurement of these
      tools of evaluation. Patients reconstructed with patellar-tendon-bone grafts have
      a higher risk of kneeling pain. There was no significant difference in the
      incidence of crepitus. Most of the outcomes following female ACL reconstructions
      showed no clinically and statistically significant difference when either
      patellar-tendon-bone or hamstring autograft was used. These included outcomes for
      anteroposterior laxity, objective knee scores, neuromuscular testing, graft
      rupture or failure, subjective knee scores, sports and activity level, and
      crepitus. This a level II study.

PMID- 30212920
TI  - ?

PMID- 30212921
TI  - ?

PMID- 30212922
TI  - Modifications and Further Development of the Original Nuss Procedure: Blessing or
      Curse?
AB  - The procedure introduced by Donald Nuss in 1997 for the treatment of pectus
      excavatum at the American Pediatric Surgical Association meeting has now been
      adopted by pediatric, thoracic, and plastic surgeons around the world. Rather
      than resection of the costal cartilages and sternal fracture, which had been
      standard practice for decades, he advocated using a metal bar to push the sternum
      into position. Reasoning that the chest wall of children is very flexible, he
      felt that resection was unnecessary. Since that time, medical centers from around
      the world have reported their experience with the procedure. There is now robust
      evidence of its safety and efficacy. As the Nuss procedure has become a standard
      treatment, indications for operation have expanded, and numerous modifications
      have been introduced. Some of these were intended to improve upon the original
      procedure, and others to adapt it to new circumstances, such as use in adults
      whose chest is not as flexible. This report reviews those modifications.

PMID- 30212923
TI  - Direct-Injection Electron Ionization-Mass Spectrometry Metabolomics Method for
      Analyzing Blueberry Leaf Metabolites That Inhibit Adult T-cell Leukemia
      Proliferation.
AB  - Metabolic profiling is often used to identify possible correlations between a
      compound's metabolic profile and biological activity. Direct-injection electron
      ionization-mass spectrometry "fingerprinting" is useful for characterizing
      biological materials. We demonstrate the utility of direct-injection electron
      ionization-mass spectrometry for metabolic profiling using 100 different extracts
      of leaves from 20 blueberry cultivars collected at 5 time points from April to
      December 2008. A qualitative direct-injection electron ionization-mass
      spectrometry method was used to profile the major and/or minor constituents in
      the blueberry leaf extracts. Blueberry leaf extracts could be distinguished by
      principal component analysis based on the absolute intensity of characteristic
      fragment ions. Twenty cultivars were categorized into four species, and the most
      appropriate discriminative marker m/z value for identifying each cultivar was
      selected statistically. Correlated m/z values indicating the collection month
      were determined in the same analysis, and air temperature variance factors were
      extracted from score plots by principal component analysis. We previously
      reported that blueberry extracts inhibit the proliferation of adult T-cell
      leukemia cells. Leaves of Vaccinium virgatum collected in December of 2008
      exhibited significantly greater inhibition of adult T-cell leukemia cell
      proliferation than other species. Highly bioactive cultivars or species were
      identified by direct-injection electron ionization-mass spectrometry metabolomics
      analysis of blueberry leaf extracts. The components extracted based on our direct
      injection electron ionization-mass spectrometry analyses could be used to
      construct a model to predict anti-adult T-cell leukemia bioactivity. This is the
      first study to report a relationship between seasonal variation and bioactivity
      of natural products using a direct-injection electron ionization-mass
      spectrometry metabolomics method.

PMID- 30212924
TI  - Marfan syndrome combined with huge abdominal aortic aneurysm size of 20 * 11 cm:
      A case report of surgical approach.
AB  - RATIONALE: Abdominal aortic aneurysm is one of the most common aneurisms.
      Patients presenting with secondary back pain should be given prompt medical
      attention. Herein, a rare case of a giant abdominal aortic aneurysm that was
      successfully treated with surgery is described. PATIENT CONCERNS: A 33-year-old
      Chinese male suffered from Marfan syndrome combined with giant abdominal aortic
      aneurysm, and presented with back pain, fever, nausea, vomiting, abdominal
      distention, and constipation. After undergoing numerous tests, the patient
      underwent an abdominal aortic aneurysm resection coupled with artificial graft
      bypass. The patient's recovery was smooth, and he was discharged 14 days after
      the operation in stable condition. DIAGNOSIS: Abdominal aortic aneurysm.
      INTERVENTIONS: The patient underwent a surgery involving mass resection and
      artificial graft bypass. OUTCOME: The patient was discharged 14 days after
      surgery in stable condition. LESSONS: Giant abdominal aortic aneurysms are rarely
      seen, and aneurysmectomy associated with prosthetic vascular graft repair is an
      effective and standard treatment for such aneurysms.

PMID- 30212925
TI  - Combined transbronchoscopic needle aspiration (TBNA) and rapid on-site
      cytological evaluation (ROSE) for diagnosis of tuberculous mediastinal
      lymphadenitis: A case report.
AB  - INTRODUCTION: The diagnosis of tuberculous mediastinal lymphadenitis remains a
      challenge, and the use of transbronchoscopic needle aspiration (TBNA) combined
      with rapid on-site cytological evaluation (ROSE) is still unclear. A case of
      tuberculous mediastinal lymphadenitis was illustrated to show the diagnostic
      value of TBNA and ROSE. CASE PRESENTATION: In this case report, we presented a
      typical case of a 44-year-old male who underwent obvious odynophagia and mild
      symptom of dyspnea. One isolated mass positioned on posterior mediastinum was
      examined as positive discovery. Finally, he was diagnosed with tuberculous
      mediastinal lymphadenitis by using TBNA combined with ROSE and treated with anti
      TB. CONCLUSIONS: TBNA is an efficacious and safe approach, which is worth
      popularizing for the clinical diagnosis of mediastinal masses. Meanwhile, ROSE is
      useful to reduce the numbers of needle passes during TBNA. We aimed to emphasize
      2 key points in this case report. Firstly, a rare symptom of Tuberculosis in
      adults was supported by the patient. Secondly, TBNA combined with ROSE is useful
      for the diagnosis of tuberculous mediastinal lymphadenitis.

PMID- 30212926
TI  - The association between transforming growth factor beta1 polymorphism and
      susceptibility to pulmonary fibrosis: A meta-analysis (MOOSE compliant).
AB  - Although many studies have investigated the association of single nucleotide
      polymorphisms (SNPs) in transforming growth factor beta1 (TGF-beta1) gene with
      pulmonary fibrosis (PF), but their association is still controversial. To clarify
      this, we performed a meta-analysis.Studies related to TGF-beta1 and PF were
      retrieved from PubMed, Medline, Embase, Scopus, and Wanfang (up to November 30,
      2017). We targeted TGF-beta1 SNPs that have been reported by >=3 studies to be
      included in the current meta-analysis, resulting in only 1 final SNP (rs1800470).
      The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in the
      models of allele comparison (T vs C), homozygote comparison (TT vs CC), dominant
      (TT vs TC + CC), recessive (TT + TC vs CC) to evaluate the strength of the
      associations.A total of 7 case-control studies were included in this meta
      analysis. Overall, no significant association between TGF-beta1 rs1800470 and PF
      was found (T vs C: OR [95% CI] = 0.96 [0.80, 1.15]; TT vs CC: 0.87 [0.61, 1.22];
      TT vs TC + CC: 0.80 [0.62, 1.04]; TT + TC vs CC: 1.13 [0.83, 1.54]). In subgroup
      analyses by ethnicity or original disease, no statistically significant
      association between TGF-beta1 rs1800470 polymorphisms and PF was
      demonstrated.This meta-analysis revealed that TGF-beta1 rs1800470 polymorphism
      was not associated with susceptibility to PF development.

PMID- 30212928
TI  - Effect of omega 3 fatty acids on C-reactive protein and interleukin-6 in patients
      with advanced nonsmall cell lung cancer.
AB  - This study investigated the anti-inflammatory effects of omega 3 fatty acids
      (O3FAs) for patients with advanced nonsmall cell lung cancer (ANSCLC).A total of
      137 patients with ANSCLC were included in this study. Of those, 77 patients
      underwent O3FA and were assigned to a treatment group, while 60 patients did not
      receive it, and were assigned to a control group. C-reactive protein (CRP), and
      interleukin (IL)-6 levels, as well as the levels of tumor necrosis factor-alpha
      (TNFalpha) and prostaglandin E2 (PGE2) were checked. In addition, nutritional
      status and quality of life were also evaluated. All patients in the treatment
      group received a total of 6 weeks treatment.After 6 weeks treatment, patients in
      the treatment group exerted better outcomes in CRP and IL-6, although no
      significant differences were found in nutritional status, as well as the quality,
      compared with patients in the control group.The results of this retrospective
      study found that O3FA may change levels of CRP and IL-6, except the nutritional
      status and quality of life.

PMID- 30212927
TI  - Mediating effects of body mass index, physical activity, and emotional distress
      on the relationship between short sleep and cardiovascular disease.
AB  - The current study investigated the mediating effects of body mass index (BMI),
      physical activity, and emotional distress on the association between short sleep
      duration (<7 hours per 24-hour period) and cardiovascular disease (CVD) and risk
      factors.We used data from the National Health Interview Survey, an ongoing
      nationally representative cross-sectional study of noninstitutionalized US adults
      (>=18 years) from 2004 to 2013 (N = 206,049). Participants provided information
      about anthropometric features (height and weight), sociodemographic factors,
      health behaviors (smoking and physical activity), emotional distress, and
      physician-diagnosed health conditions, including hypertension, coronary heart
      disease, diabetes, heart attack, stroke, kidney disease, and cancer. Structural
      equation modeling was used to assess the mediating effects of physical activity,
      BMI, and emotional distress on the relationship between short sleep and CVDs and
      risk factors (coronary heart disease, hypertension, diabetes, chronic kidney
      disease, heart attack, and stroke).Of the sample, 54.7% were female, 60.1%
      identified as white, 17.7% as Hispanic, and 15.4% as black. The mean age of the
      respondents was 46.75 years (SE = 0.12), with a mean BMI of 27.11 kg/m (SE =
      0.02) and approximately 32.5% reported short sleep duration. The main
      relationship between short sleep and CVD and risk factors was significant (beta =
      0.08, P < .001), as was the mediated effect via BMI (indirect effect = 0.047, P <
      .001), emotional distress (indirect effect = 0.022, P < .001), and physical
      activity (indirect effect = -0.022, P = .035), as well as after adjustment for
      covariates, including age, race, sex, marital status, and income: short sleep and
      CVD (B = 0.15; SE = 0.01; P < .001), BMI (B = 0.05; SE = 0.00; P < .001),
      emotional distress (B = 0.02; SE = 0.00; P < .001), and physical activity (B =
      0.01; SE = 0.00; P < .001).Our findings indicate that short sleep is a risk
      factor for CVD and that the relationship between short sleep and CVD and risk
      factors may be mediated by emotional distress and obesity, and negatively
      mediated by physical activity.

PMID- 30212930
TI  - Gene co-expression network analysis identifies the hub genes associated with
      immune functions for nocturnal hemodialysis in patients with end-stage renal
      disease.
AB  - End-stage renal disease (ESRD) is the final stage of chronic kidney disease in
      which the kidney is not sufficient to meet the needs of daily life. It is
      necessary to understand the role of genes expression involved in ESRD patient
      responses to nocturnal hemodialysis (NHD) and to improve the immunity
      responsiveness. The aim of this study was to investigate novel immune-associated
      genes that may play important roles in patients with ESRD.The microarray
      expression profiles of peripheral blood in patients with ESRD before and after
      NHD were analyzed by network-based approaches, and then using Gene Ontology (GO)
      and Kyoto Encyclopedia of Genes and Genomes pathway analysis to explore the
      biological process and molecular functions of differentially expressed genes.
      Subsequently, a transcriptional regulatory network of the core genes and the
      connected transcriptional regulators was constructed. We found that NHD had a
      significant effect on neutrophil activation and immune response in patients with
      ESRD.In addition, Our findings suggest that MAPKAPK3, RHOA, ARRB2, FLOT1, MYH9,
      PRKCD, RHOG, PTPN6, MAPK3, CNPY3, PI3KCG, and PYGL genes maybe potential targets
      regulated by core transcriptional factors, including ARNT, C/EBPalpha, CEBPA,
      CREB1, PSG1, DAND5, SP1, GATA1, MYC, EGR2, and EGR3.

PMID- 30212929
TI  - CYP2D6 genotypes in revolving door patients with bipolar disorders: A case
      series.
AB  - RATIONALE: In psychiatric disorders, interindividual differences in cytochrome
      P450 (CYP)2D6 (CYP2D6) enzymatic activity could be responsible of adverse drug
      reactions (ADRs) and therapeutic failures (TFs) for CYP2D6-metabolized drugs,
      contributing to the periodical hospital readmissions of the revolving door (RD)
      condition. PATIENT CONCERNS: We investigated CYP2D6 genotypes in a controlled
      series of 5 consecutive RD patients with Bipolar Disorder (BD). DIAGNOSES:
      Psychiatric patients affected by Bipolar Disorder. INTERVENTIONS: We defined TFs
      as a difference at the Brief Psychiatric Rating Scale score DeltaBPRS < 25% at
      each 1-week of stable treatment, and ADRs as the onset of extrapyramidal symptoms
      and/or metabolic impairment with weight gain. OUTCOMES: At 3 months, a mean
      number of 2.75 +/- 1.26 ADR and a mean DeltaBPRS score of 16.07 +/- 0.05% were
      observed. At 6 months of follow-up, compared to the only patient without BD
      (DeltaBPRS < 32.10%), BD patients (n = 4) showed TFs (DeltaBPRS < 25%). CYP2D6
      genotyping revealed intermediate metabolizer phenotypes for BD patients and an
      extensive metabolizer phenotype for the patient without BD. In BD patients, the
      ratio of drugs maintained/discontinued for TFs or ADRs was 1.75 for non-CYP2D6
      versus 0.33 for CYP2D6 interacting drugs, while the proportion of ADR:TF was 0:4
      versus 6:3. LESSONS: Our findings may suggest that CYP2D6 clinically relevant
      genotypes may be involved in the unwanted outcomes observed in RD patients with
      BD.

PMID- 30212931
TI  - Exploring the molecular mechanism associated with breast cancer bone metastasis
      using bioinformatic analysis and microarray genetic interaction network.
AB  - BACKGROUND: Bone metastases are common in advanced breast cancer patients and
      frequently leading to skeletal-related morbidity and deterioration in the quality
      of life. Although chemotherapy and hormone therapy are able to control the
      symptoms caused by bone destruction, the underlying molecular mechanisms for the
      affinity of breast cancer cells towards skeletal bones are still not completely
      understood. METHODS: In this study, bioinformatic analysis was performed on
      patients' microarray gene expression data to explore the molecular mechanism
      associated with breast cancer bone metastasis. Microarray gene expression profile
      regarding patients with breast cancer and disseminated tumor cells was downloaded
      from Gene Expression Omnibus (GEO) database (NCBI, NIH). Raw data were normalized
      and differently expressed genes were identified by using Significance Analysis of
      Microarrays (SAM) methods. Protein interaction networks were expanded using
      String. Moreover, molecular functions, biological processes and signaling pathway
      enrichment analysis were performed using Gene Ontology (GO) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG). RESULTS: We identified 66
      differentially expressed genes. After submitting the set of genes to String,
      genetic interaction network was expanded, which consisted of 110 nodes and 869
      edges. Pathway enrichment analysis suggested that adhesion kinase, ECM-receptor
      interaction, calcium signaling, Wnt pathways, and PI3K/AKT signaling pathway are
      highly associated with breast cancer bone metastasis. CONCLUSION: In this study,
      we established a microarray genetic interaction network associated with breast
      cancer bone metastasis. This information provides some potential molecular
      therapeutic targets for breast cancer initiation and progression.

PMID- 30212932
TI  - Influential factors on cognitive performance in middle-aged cohort: Third
      National Health and Nutrition Examination Survey-based study.
AB  - Aging-associated cognitive decline is closely linked to illness, dementia,
      increased mortality, and is a major health and social issue. The purpose of this
      study was to determine modifiable factors associated with cognitive
      performance.We analyzed data from a random sample of participants of the Third
      National Health and Nutrition Examination Survey, which is a cross-sectional
      survey, of the US population, aged 20 to 59 years, who underwent computer-based
      neurocognitive testing. There were 5 outcome measures in 3 neurocognitive tests:
      the mean of simple reaction time test, the mean total latency of the symbol digit
      substitution test (SDST), the average number of errors of the SDST, the average
      trials to criterion of the serial digit learning test (SDLT), and the average
      total score of the SDLT.Socioeconomic status, including older age, black
      ethnicity, lower income ratio, and lower education level, were associated with
      poorer neurocognitive function in all analyzed tests. In addition, participants
      with poor health, nonsmokers, and nondrinkers performed worse in all administered
      tests compared with individuals with good health, smokers, and participants
      consuming alcoholic beverages. Dietary and biochemical characteristics of the
      blood were not consistently associated with neurocognitive performance.Our
      results indicate that socioeconomic factors, health-related and dietary habits,
      biochemical parameters of the blood, and job category were associated with
      neurocognitive performance in visual attention, learning, and concentration in a
      large, nationally representative sample of healthy, ethnically diverse 20 to 59
      year-olds. Future studies are needed to understand the mechanisms of cognitive
      aging and the factors that contribute to its individual differences.

PMID- 30212933
TI  - Comprehensive analysis of lysine crotonylation in proteome of maintenance
      hemodialysis patients.
AB  - INTRODUCTION: Histone post-translational modifications (PTMs) carry epigenetic
      information to regulate diverse cellular processes at the chromatin level.
      Crotonylation, one of the most important and common PTMs, plays a key role in the
      regulation of various biological processes. However, no study has evaluated the
      role of lysine crotonylation in maintenance hemodialysis patients (MHP). METHODS:
      Here, we comparatively evaluated the crotonylation proteome of normal controls
      (NC) and MHP using liquid chromatography tandem mass spectrometry (LC-MS/MS)
      coupled with highly sensitive immune-affinity purification. RESULTS: A total of
      1109 lysine modification sites distributed on 347 proteins were identified,
      including 93 and 252 crotonylated upregulated and downregulated proteins,
      respectively. Thus, a decrease in crotonylation of histone proteins was observed
      in patients with kidney failure undergoing maintenance hemodialysis. Intensive
      bioinformatic analysis revealed that most of the crotonylated proteins were
      distributed in the cytoplasm, nucleus, mitochondria, and extracellular region.
      Gene ontology enrichment analysis showed that the crotonylated proteins were
      significantly enriched in the platelet alpha granule lumen, platelet
      degranulation, and cell adhesion molecule binding. In addition, protein domain,
      including fibrinogen alpha/beta/gamma chain, zinc finger, and WD40-repeat
      containing domain, were significantly enriched in crotonylated proteins. Kyoto
      Encyclopedia of Genes and Genomes (KEGG)-based functional enrichment analysis
      revealed that crotonylated proteins were enriched in complement and coagulation
      cascades, cardiac muscle contraction, and hematopoietic cell lineage, all of
      which have important associations with hemodialysis complications. CONCLUSIONS:
      This is the first report on the global crotonylation proteome of MHP. Lysine
      crotonylation was found to play important regulatory roles in pathophysiological
      processes in MHP.

PMID- 30212934
TI  - Correlation between esophageal pH-metry and esophagitis in gastroesophageal
      reflux disease in children.
AB  - Gastroesophageal reflux (GER) is the intermittent or permanent passage of stomach
      content into the esophagus and gastroesophageal reflux disease (GERD) is the
      reflux which triggers a whole set of symptoms or complications. The study
      compares the 24-hours esophageal pH-metry, used for diagnosis of the GERD, with
      the esophagitis degree observed at the upper digestive endoscopy.72 children were
      included, aged over 4 years old, admitted in a pediatric gastroenterology
      regional center in Northeast Romania, diagnosed with GERD by 24 hours pH-metry
      (with a positive Boix-Ochoa score), which also underwent the upper digestive
      endoscopy.Out of the 72 children diagnosed with GERD, 47 (65.28%) had grade A
      esophagitis and 25 (34.72%) grade B esophagitis. In GERD associated with grade B
      esophagitis the Boix-Ochoa score is statistically significant higher, compared
      with the GERD associated with grade A esophagitis (F = 9.76, P = .0036, 95%
      CI).Upper digestive endoscopy performed in patients with gastroesophageal reflux
      disease shows the constant presence of esophagitis at all patients. There were
      only grade A and B esophagitis due to the fact that they are young patients with
      a relative short history of the disease. The correlation tests show a perfect
      parallel between the pH-metry scores and the endoscopic lesion. The correlation
      is so accurate that the pH-metry scores can be sufficient to prove GERD and the
      grade of esophagitis, the upper digestive endoscopy being reserved only for the
      cases that does not respond to the medical treatment or have other complications.

PMID- 30212935
TI  - A new modified bone grafting technique for periodontally accelerated osteogenic
      orthodontics.
AB  - The aim of this study was to introduce an improved surgical technique using a
      pouch design and tension-free wound closure for periodontally accelerated
      osteogenic orthodontics (PAOO) in the anterior alveolar region of the
      mandible.Patients with bone dehiscence and fenestrations on the buccal surfaces
      of the anterior mandible region underwent the modified PAOO technique (using a
      pouch design and tension-free closure). Postoperative symptoms were evaluated at
      1 and 2 weeks intervals following the procedure. Probing depth (PD), gingival
      recession depth (GRD), and clinical attachment level (CAL) were assessed at the
      gingival recession sites at baseline, postoperative 6 and 12 months. Cone-beam
      computerized tomography (CBCT) was used for quantitative radiographic analyses at
      baseline, 1 week and 12 months after bone-augmentation procedure.The sample was
      composed of a total of 12 patients (2 males and 10 females; mean age, 21.9 years)
      with 72 teeth showing dehiscence/fenestrations and 17 sites presenting with
      gingival recessions. Clinical evaluations revealed a statistically significant
      reduction in swelling, pain, and clinical appearance from postoperative week 1 to
      week 2 (P < .05). Moreover, gingival recession sites exhibited a significant
      reduction in the GRD and an increase in CAL after surgery with mean root coverage
      of 69.8% at the end of observation period (P < .01). Both alveolar bone height
      and width increased after surgery (P < .01) and decreased during the 12-month
      follow-up (P < .01). However, compared with the baseline records, there was still
      a significant increase in alveolar bone volume (P < .01).This modified PAOO
      technique may have advantages in terms of soft and hard tissue augmentation,
      facilitating extensive bone augmentation and allowing the simultaneous correction
      of vertical and horizontal defects in the labial aspect of the mandibular
      anterior area.

PMID- 30212936
TI  - A correlation between gastrointestinal dysfunction and cirrhosis severity.
AB  - This study aims to investigate the relationship between gastrointestinal
      dysfunction (GD) and cirrhosis severity in cirrhotic patients, to provide
      evidences for the prevention and treatment of GD in cirrhotic patients.A total of
      95 cirrhotic inpatients and outpatients, who were treated in the Department of
      Gastroenterology of Xinqu Hospital of the First Affiliated Hospital of Henan
      University of Science and Technology, were enrolled in the present study, and
      assigned as the experimental group (cirrhosis group). According to Child-Pugh
      classification, these patients were divided into 3 groups: group A (n = 45),
      group B (n = 23), and group C (n = 27). Forty healthy adults who received health
      check-ups during the same period served as the control group. The
      gastrointestinal (GI) symptoms of cirrhotic patients were scored, and the fasting
      serum gastrin (GAS), motilin (MTL), and vasoactive intestinal peptide (VIP)
      levels were measured in all subjects.The potential correlations of GI symptom
      scores of patients in these cirrhosis groups with GI hormone levels and cirrhosis
      severity were analyzed. In cirrhotic patients, the GI symptom scores
      significantly increased. Furthermore, the symptom scores gradually increased
      along with the aggravation of liver damage. Moreover, serum GAS and VIP levels
      were significantly higher in the cirrhosis groups than in the control group,
      whereas MTL levels were significantly lower. These changes were significantly
      correlated with cirrhosis severity. The linear correlation analysis revealed that
      the GI symptom score was positively correlated with GAS and VIP levels, and
      negatively correlated with MTL level. In addition, the linear correlation
      analysis revealed that GI symptom score and GAS and VIP levels were positively
      correlated with cirrhosis severity, whereas MTL level was negatively correlated
      with cirrhosis severity.Cirrhotic patients have more obvious GI symptoms and
      higher GI hormone levels, which are closely correlated with the progression of
      liver cirrhosis and the degree of liver function damage.

PMID- 30212937
TI  - Ankle joint dislocation treating dislocated trimalleolar fractures accompanied
      with the complex posterior malleolus fracture without separation of the
      tibiofibular syndesmosis.
AB  - To explore the therapy of ankle joint dislocation treating dislocated
      trimalleolar fractures accompanied with the complex posterior malleolus fracture
      without separation of the tibiofibular syndesmosis and improve surgical
      results.Patients who had dislocated trimalleolar fractures accompanied with the
      complex posterior malleolus fracture without separation of the tibiofibular
      syndesmosis were retrospectively analyzed and 30 patients were enrolled the
      study. They were all treated by ankle joint dislocation and the surgical results
      were evaluated by the Baird-Jackson ankle scoring system. Longitudinal curved
      incision in medial malleolus was made in ankle joint dislocation and subluxation
      was automatically formed by appropriate traction of ankle joint. The talus and
      the distal end of internal and external malleolus were pushed the outside to form
      the lateral dislocation of the ankle joint. After fully revealed the posterior
      malleolus and distal articular surface of the tibia, the anatomical reduction of
      comminuted bones with joint cartilage and posterior malleolus was achieved by
      fixed with absorbable screw or Kirschner wire. Internal and external malleolus
      fracture was fixed by the conventional approach.The average follow-up period was
      13 months. According to the Baird-Jackson ankle scoring system, the excellent and
      good result was 28 cases, fair was 2 cases which the excellent and good rate was
      93.3% without talar necrosis in any cases.Ankle joint dislocation can achieve the
      satisfactory results in treating dislocated trimalleolar fractures accompanied
      with the complex posterior malleolus fracture without separation of the
      tibiofibular syndesmosis. Ankle joint dislocation can make joint cartilage
      restore accurately with excellent results.

PMID- 30212938
TI  - Effects of platelet-rich plasma in the treatment of plantar fasciitis: A meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Plantar fasciitis is a common cause of heel pain, which often results
      in significant morbidity. There have been several treatment options that are used
      for plantar fasciitis, including nonsteroidal anti-inflammatory drugs, orthoses,
      physical therapy, and steroid injections. OBJECTIVES: The aim of this meta
      analysis was to compare the effects of platelet-rich plasma (PRP) and other
      treatments in patients with plantar fasciitis. SEARCH METHODS: Medline, Web of
      Science, and Embase were systematically searched to identify relevant trials.
      SELECTION CRITERIA: Randomized controlled trials (RCTs) that compared the effects
      of PRP and other treatments on plantar fasciitis were included. DATA COLLECTION
      AND ANALYSIS: The main outcomes included changes from baseline in visual analog
      scale (VAS) score, American Orthopaedic Foot and Ankle Society Score (AOFAS), and
      Roles-Maudsley score (RMS). Results were expressed as weight mean difference
      (WMD) with 95% confidence interval (95% CI). The meta-analysis was performed
      using a fixed-effects or random-effects model according to heterogeneity. MAIN
      RESULTS: Ten RCTs involving a total of 445 patients with plantar fasciitis were
      included. Among these studies, 9 compared PRP with steroid, and 1 compared PRP
      with whole blood.Four studies were categorized as being at low risk of bias, and
      the remaining 6 as being at unclear risk of bias.Pooled estimates suggested that
      PRP had greater changes in VAS and AOFAS scores than other treatments. However,
      it had no benefit effect in the RMS.Subgroup analysis for VAS and AOFAS showed
      that PRP had superior effect than other treatments at 12 months, but not at the
      1, 3, 6 months.Subgroup analysis based on treatment regimens demonstrated that
      PRP was more effective than steroid in the change from baseline in AOFAS, but not
      in VAS and RMS scores. AUTHORS' CONCLUSION: PRP was as effective as other
      treatments in reducing pain and improving function in patients with plantar
      fasciitis. Subgroup analysis indicated that PRP had better effect than steroid in
      AOFAS Score and its effect was durable in a long term. However, considering the
      potential limitations in this study, more large-scale RCTs are needed to confirm
      the current findings.

PMID- 30212939
TI  - Anomalous course and stenosing tenosynovitis of the extensor pollicis longus
      tendon at the radial styloid process: A case report.
AB  - RATIONALE: Anomalous course and tenosynovitis of extensor pollicis longus (EPL)
      tendon is a rare condition that presents clinical symptoms very similar to de
      Quervain's disease. Herein we report a case of anomalous course and tenosynovitis
      of the extensor pollicis longus (EPL) tendon associated with symptoms of de
      Quervain's disease. PATIENT CONCERNS: A 44-year-old right-handed man visited the
      clinic because of radial pain associated with the left wrist, which was
      aggravated during the previous 10 days. The patient tested positive on the
      Finkelstein's test and displayed a limited range of motion of the left wrist.
      Motion of the thumb and wrist aggravated pain. DIAGNOSES: Magnetic resonance
      imaging (MRI) of the left wrist suggested mild tenosynovitis at the third
      extensor compartment and intersection syndrome. However, clinical symptoms failed
      to match the MRI findings. INTERVENTIONS: A zig-zag skin incision on the radial
      styloid process was made. The operative findings revealed stenosing tenosynovitis
      with partial tearing. Retraction of the tendon extended the thumb interphalangeal
      joint, suggesting that the tendon was the EPL tendon rather than EPB tendon.
      After operation, we reviewed the MRI of the patient, which revealed that the
      oblique course of the EPL tendon originated from the ulnar side of the forearm to
      the radial styloid at the radial and proximal site of Lister's tubercle. No EPB
      tendon was present. OUTCOMES: At 12 months of follow-up, the patient's radial
      styloid process was completely asymptomatic and resumed full daily activities.
      LESSONS: Anomalous course of the EPL tendon is rarely reported associated with
      similar symptoms of de Quervain's disease. However, the knowledge and
      understanding of this potential anomaly in the course of EPL tendon is very
      important for the treatment of de Quervain's disease to decrease patient
      dissatisfaction after surgery.

PMID- 30212940
TI  - Successful retrieval of a plastic bead from the airway of a child by flexible
      bronchoscopy and a balloon-tipped catheter: A case report and literature review.
AB  - RATIONALE: Bronchial foreign body aspiration is a critical condition that
      jeopardizes the respiratory function of children. Prompt diagnosis and removal of
      the foreign body can reduce occurrence of foreign body complications and
      mortality. Aspiration of spherical plastic beads is rare, and the bead is
      difficult to retrieve. PATIENT CONCERNS: An 8-year-old girl developed cough,
      transient throat wheezing, and intermittent cough after she accidentally inhaled
      a plastic bead 7 hours ago. Chest computed tomography scan revealed a round
      shadow 1.2 cm in diameter in the right main bronchus. DIAGNOSES: Foreign body in
      the right main bronchus. INTERVENTIONS: Retrieval by balloon-tipped catheter via
      flexible bronchoscopy was undertaken. OUTCOMES: The bead was successfully
      retrieved and the child recovered uneventfully. LESSONS: Foreign body aspiration
      in children constitutes a medical emergency in severe cases. Flexible
      bronchoscopy and balloon-tipped catheter retrieval can be used as an effective
      noninvasive treatment for aspiration of plastic beads.

PMID- 30212941
TI  - Spontaneous rupture of flexor pollicis longus tendon by tendolipomatosis in
      proximal phalanx: A case report.
AB  - RATIONALE: Spontaneous flexor pollicis longus (FPL) tendon rupture is rarely
      reported. Although there are several studies investigating spontaneous FPL tendon
      rupture, the exact etiology of spontaneous rupture is unclear. Here, we present a
      case of unusual spontaneous FPL tendon rupture due to tendolipomatosis. PATIENT
      CONCERNS: A 64-year-old right-handed retired male teacher was referred to our
      clinic with an inability to flex the interphalangeal joint of his left thumb.
      DIAGNOSIS: Magnetic resonance imaging (MRI) revealed complete FPL tendon rupture
      at the level of the distal one-third of the proximal phalanx. INTERVENTIONS: With
      the patient under general anesthesia, the FPL tendon was explored through a volar
      zig-zag incision. During the operation, the FPL tendon was found to be ruptured
      completely. Gross examination revealed a slightly yellowish denaturated tissue at
      the distal end of the ruptured tendon. We excised the denaturated tissue from the
      distal end of the ruptured tendon and sent it for histological examination. FPL
      tendon was repaired primarily via modified Becker method. Histopathological
      examination revealed normal vasculature in the tendon tissue and degenerative
      changes associated with lipid deposits in the tendon tissue. OUTCOMES: At 12
      month follow-up, the patient was completely asymptomatic and had excellent IP
      joint range of motion (0 degrees  to 40 degrees ) in his left thumb. The wrist
      grip strength was 30 kg (28 kg in the Rt.) and the thumb pinch strength was 5.7
      kg (4.7 kg in the Rt.). The Quick DASH score was 0. LESSONS: Spontaneous rupture
      of the FPL tendon, attributed to degenerative changes caused by tendolipomatosis,
      is the first report of its kind, in the authors' opinion. Hence we recommend to
      perform the histopathological examination of the debrided tissue from the ends of
      the ruptured tendon, if the physicians couldn't know the exact cause of the
      spontaneous intratendinous rupture of the FPL. And early diagnosis followed by
      debridement and primary tendon repair provides an effective outcome.

PMID- 30212942
TI  - Sacral agenesis combined with spinopelvic dissociation: A case report and
      literature review.
AB  - INTRODUCTION: Sacral agenesis is a rare congenital disease with radiologic
      manifestation of sacrum deformity. Its clinical manifestations include
      spinopelvic instability due to sacroiliac joint deformity, spinal rotation,
      scoliosis, difficulties in walking, and claudication. Surgical intervention aims
      to prevent further deformity progression and to improve the patients' walking
      function. It is challenging to achieve solid arthrodesis for this congenital
      disease, and fusion failure could aggravate deformity. CASE PRESENTATION: We
      retrospectively studied one case of a 12-year-old girl with sacral agenesis
      combined with spinopelvic dissociation and spinal scoliosis. She was presented
      with intermittent lumbosacral pain and worsening walking instability. We
      reconstructed the posterior pelvic ring through 1 iliac screw implanted in the
      bilateral posterior superior iliac spine, and the preflexed connecting rod was
      tightly locked with bilateral screws through the opening at the right spinal
      process of S2. With this method, bilateral ilia and sacrum were integrated and
      hemipelvic floating could be corrected. Bone fusion was achieved between the
      bilateral ilia and the sacrum. CONCLUSION: Ilium-sacrum-ilium internal fixation
      and fusion for treating sacral agenesis combined with spinopelvic dissociation
      could achieve sacroiliac joint fusion. It is easy to perform and could cause
      little trauma while preserving the lumbar motion segment, which will provide new
      insight for treating sacral agenesis.

PMID- 30212943
TI  - Association between dietary carrot intake and breast cancer: A meta-analysis.
AB  - BACKGROUND: We aimed to estimate the association between dietary carrot intake
      and risk of breast cancer by conducting a meta-analysis of epidemiologic studies.
      METHODS: Relevant studies were identified by searching databases through
      September 2017. We included studies that reported risk estimates with 95%
      confidence intervals for the association between dietary carrot intake and breast
      cancer risk. Random-effects models were used to calculate the summary risk
      estimates. Publication bias was estimated using Begg's funnel plot and Egger's
      regression asymmetry test. RESULTS: A total of 10 articles met the eligibility
      criteria and were included in the meta-analysis involving 13,747 cases. The
      combined odds ratios (ORs) of breast cancer for the highest compared with the
      lowest dietary carrot intake was 0.79 (95% CI: 0.68, 0.90), and a significant
      heterogeneity was observed. In the subgroup analyses separated by study design,
      the inverse associations were more pronounced in the case-control studies than in
      the cohort studies, while the associations did not significantly differ by
      geographical region, study quality, exposure assessment. Omission of any single
      study had little effect on the combined risk estimate. CONCLUSION: The overall
      current literatures suggested that dietary carrot intake was associated with
      decreased risk of breast cancer.

PMID- 30212945
TI  - Possibility of venoarterial extracorporeal membranous oxygenator being a bridging
      therapy for hemodynamic deterioration of pulmonary tumor thrombotic
      microangiopathy prior to initiating chemotherapy: A case report.
AB  - RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but lethal
      complication of carcinoma, defined as non-occlusive pulmonary tumor embolism
      complicated by fibrocellular intimal proliferation of the small pulmonary
      arteries, with eventual occlusion of the pulmonary arteries. Hemodynamic
      deterioration caused by this condition leads to high mortality. PATIENT CONCERNS:
      A 46-year-old woman who had undergone radiation therapy for anaplastic
      oligoastrocytoma and who was taking temozolomide presented with cough and
      palpitations. DIAGNOSES: A 12-lead electrocardiogram showed sinus tachycardia and
      SIQIII TIII, with negative T in V1-3. Ultrasound cardiography showed a distended
      right ventricle. Enhanced chest computed tomography showed no significant
      thrombus in the major pulmonary artery. The patient's condition deteriorated the
      next morning, with her blood pressure decreasing to 40 mmHg and her SpO2
      unmeasurable. She suffered cardiac arrest. INTERVENTIONS: We initiated
      venoarterial extracorporeal membranous oxygenation (VA-ECMO) and her blood
      pressure increased to 80 mmHg. Her hemodynamic status stabilized and she was
      weaned off VA-ECMO on intensive care unit (ICU) day 3. OUTCOMES: Gastroesophageal
      endoscopy on ICU day 4 revealed gastric cancer (Borrman type IV), and she
      arrested again and died on ICU day 5. Autopsy confirmed gastric cancer and PTTM.
      LESSONS: VA-ECMO rapidly stabilized the hemodynamic status of this patient with
      PTTM, and may thus be a possible bridging therapy for deterioration of PTTM prior
      to initiating imatinib.

PMID- 30212944
TI  - Wnt2 knock down by RNAi inhibits the proliferation of in vitro-cultured human
      keloid fibroblasts.
AB  - To study the effect of knocking down wingless-related MMTV integration site 2
      (Wnt2) expression by RNAi on the growth and signaling pathways of ex vitro
      cultured keloid fibroblasts (KFB).Human KFB were isolated from 10 keloid patient
      specimens. The KFB cells were then transfected with 4 pairs of small interfering
      RNA (siRNA) targeting human Wnt2, respectively. Reverse transcriptase-polymerase
      chain reaction and Western blot analysis were conducted to verify the knock down
      of Wnt2, and the expression of beta-catenin glycogen synthase kinase-3beta (GSK
      3beta) and cyclin D1 were examined.siRNA Wnt2 transfection (siWnt2) resulted in
      the significant inhibition of Wnt2 expression at both the mRNA and protein
      levels. The expression of beta-catenin, GSK-3beta, p-GSK-3beta, and cyclin D1 at
      the protein level also decreased in siWnt2 cells. siWnt2 resulted in a
      substantially slower growth and significant delay in cell doubling time of the
      KFB cells compared with control groups. Further, the siRNA knock down of GSK
      3beta and beta-catenin resulted in slower proliferation rates, respectively.Wnt2
      siRNA has an inhibitive effect on keloid fibroblast proliferation, which may be a
      potential therapeutic approach for keloid and other human fibrotic diseases.

PMID- 30212946
TI  - Nonsteroidal anti-inflammatory drugs use and risk of Parkinson disease: A dose
      response meta-analysis.
AB  - Previous studies have indicated that nonsteroidal anti-inflammatory drugs
      (NSAIDs) use is associated with Parkinson disease risk, but presented
      controversial results.Medline, Embase, Web of Science, and the Cochrane Database
      were searched update to November 2017. Key data were extracted from eligible
      studies. A dose-response meta-analysis was conducted for synthesizing data from
      eligible studies.Fifteen eligible studies were included in this meta-analysis.
      NSAIDs use was not associated with Parkinson disease risk [relevant risk (RR):
      0.06; 95% confidence interval (95% CI), 0.91-1.02]. Subgroup analysis showed that
      aspirin use (RR: 1.14; 95% CI, 0.98-1.30) or ibuprofen use (RR: 1.01; 95% CI,
      0.88-1.17) was not associated with Parkinson disease risk; however, the use of
      non-aspirin NSAIDs was significantly associated with Parkinson disease risk
      (RR:0.91; 95% CI, 0.84-0.99). Furthermore, NSAIDs use was not associated with the
      risk of Parkinson disease in female (RR: 0.99; 95% CI, 0.83-1.17) and male (RR:
      1.01; 95% CI, 0.88-1.16). In addition, a dose-response showed per 1 number of
      prescription incremental increase in NSAIDs use was not associated with the risk
      of Parkinson disease (RR: 0.96; 95% CI, 0.91-1.02), per 1 year of duration of
      NSAIDs use incremental increase was not associated with the risk of Parkinson
      disease (RR: 0.98; 95% CI, 0.92-1.03), and per 1 dosage of NSAIDs use incremental
      increase was not associated with the risk of Parkinson disease (RR: 0.98; 95% CI,
      0.95-1.02).NSAIDs use was not associated with the risk of Parkinson disease. The
      potency and the cumulative NSAIDs use did not play critical roles.

PMID- 30212947
TI  - Effect of linezolid on serum PCT, ESR, and CRP in patients with pulmonary
      tuberculosis and pneumonia.
AB  - BACKGROUND: The continuous development of drug-resistant tuberculosis in recent
      years has brought new attention to tuberculosis. linezolid is usually used to
      treat infection in patients with pulmonary tuberculosis and pneumonia, for it has
      good effects on Mycobacterium tuberculosis, and has strong antibacterial activity
      on the drug-resistant strain. This study aims to investigate the effects of
      linezolid on serum procalcitonin (PCT), erythrocyte sedimentation rate (ESR), and
      C-reactive protein (CRP) in patients with pulmonary tuberculosis and pneumonia.
      METHODS: Forty patients with pulmonary tuberculosis and pneumonia were divided
      into 2 groups: observation group (n = 20), patients treated with linezolid;
      control group (n = 20), patients treated with moxifloxacin. At 14 days, one month
      and 3 months of treatment, changes in serum PCT, ESR, CRP, and bacterial
      eradication rate (negative conversion rate) were compared between the 2 groups,
      and the incidence of adverse reactions was compared. RESULTS: Serum PCT, ESR, and
      CRP in the 2 groups were significantly lower after 14 days of treatment than
      before treatment (P < .05), the decrease was more significant in the observation
      group, and the differences in ESR and CRP were statistically significant (t =
      2.199, 2.494, P < .05). Furthermore, the negative conversion rate was higher in
      the observation group, but the difference was not statistically significant (P >
      .05). At one month of treatment, serum PCT, ESR, and CRP were lower in the
      observation group, and the difference in CRP was statistically significant (t =
      3.274, P < .05). Furthermore, the negative conversion rate was slightly higher in
      the observation group, but the difference was not statistically significant (P >
      .05). At 3 months of treatment, differences in PCT, ESR, and CRP were not
      statistically significant, and the negative conversion rate was the same between
      the 2 groups. Furthermore, the incidence of adverse reactions was higher in the
      observation group, but all were mild, and the differences between these 2 groups
      were not statistically significant (P > .05). CONCLUSION: In the treatment of
      tuberculosis and pneumonia, linezolid can improve serum PCT, ESR, and CRP levels,
      and eradicate bacteria. However, adverse reactions should be strictly monitored
      to ensure its safety.

PMID- 30212948
TI  - Effect of rational emotive behavior therapy on stress management and irrational
      beliefs of special education teachers in Nigerian elementary schools.
AB  - BACKGROUND/OBJECTIVE: From a rational emotive behavior therapy viewpoint, stress
      related disorders originate from irrational beliefs and self-defeating
      philosophies and attitude. Individuals affected by stress are different from
      those ones with neurotic problems mainly because the stressed individuals have
      irrational beliefs about specific, short-term, or more readily identifiable
      events, in contrast to the more mundane and diffuse difficulties faced by
      neurotic persons. The present study aimed to examine the impact of a rational
      emotive behavior therapy (REBT) intervention on the stress levels and irrational
      beliefs among special education teachers in elementary schools in Nigeria.
      METHODS: We employed a group randomized controlled trial design for this study.
      Eighty six participants recruited from elementary schools in the South-eastern
      part of the country were randomly assigned to either a treatment group (n = 43)
      or no-intervention control group (n = 43). We used the REBT Stress Management
      Manual to conduct the intervention. Stress levels and irrational beliefs were
      assessed using self-report questionnaires. Participants in the treatment group
      took part in the REBT program for 12 weeks and a follow-up program for 2 weeks.
      Analysis of the data was completed through a 2 * 3 within * between-subjects
      repeated measures analysis of variance, and independent samples t test. RESULTS:
      Results showed that the REBT group experienced a significant mean decline in
      stress levels and their beliefs shifted to rational ones both at post-treatment
      and follow-up. In contrast, the participants in the no-intervention control group
      showed no improvements at either posttreatment or follow-up sessions. CONCLUSION:
      Rational-emotive behavior therapy is an effective therapeutic modality that can
      be applied by REBT clinicians for the management of stress. Additional clinical
      assessments will be necessary to further confirm the impact of an REBT
      intervention on teachers' stress management and irrational beliefs in Nigerian
      elementary school setting.

PMID- 30212949
TI  - Primary poorly differentiated lacrimal gland adenocarcinoma in left ocular
      region: A rare case report.
AB  - RATIONALE: Primary poorly differentiated lacrimal gland adenocarcinoma in the
      orbital region is an extremely rare type of neoplasm with only 1 related case in
      the literature. Its high grade of malignancy makes the timely data reported
      necessary. Hence, we present an extremely rare disease with biopsy results and
      recommendations on clinical treatment in an elderly male with Chinese descent.
      PATIENT CONCERNS: A 66-year-old Chinese man presented with swelling in the left
      ocular region and eyeball proptosis. On physical examination, the patient had
      redness, tenderness, and swelling of the left eye. A surgical incision was noted
      on the left orbital region. Left eye movements were restricted. DIAGNOSES:
      Immunohistochemical examination revealed pan-cytokeratin (PCK, +), p63 (partial,
      +), cytokeratin 7 (CK7, +), cytokeratin 14 (CK14, +), epithelial membrane antigen
      (EMA, +), protein expressed by erythroblast transformation-specific related gene
      (ERG, -), S-100 (, -), Epstein-Barr virus-encoded small RNA (EBER, -), smooth
      muscle actin (SMA, -), and Ki-67 (with a proliferation index approximately 40%).
      After carefully reviewed the manifestations, imaging findings, and
      immunohistochemical evidences, a diagnosis of poorly differentiated
      adenocarcinoma of lacrimal gland was made. INTERVENTION: Based on the gene
      sequencing results, we started the patient with an intensive PF chemotherapy
      including a combination of cisplatine, fluorouracil, and epirubicin. Two months
      later, radiotherapy was introduced to the therapy regimen. OUTCOMES: The patient
      responded well to the treatment without severe adverse events. MRI scan showed
      remarkable remission. LESSONS: This rare case report will help raise the
      awareness of high grade lacrimal gland cancer, and subsequently aid the diagnosis
      in future cases. Positive immunohistochemical markers of CK7, CK14, EMA, p63, and
      high proliferation index of Ki-67 can help establishing a diagnosis, and
      cisplatine-fluorouracil program is proved feasible. We share the difficulties we
      have encountered, hoping to improve patient care in the future.

PMID- 30212950
TI  - Clinical outcome comparison of polymethylmethacrylate bone cement with and
      without mineralized collagen modification for osteoporotic vertebral compression
      fractures.
AB  - A retrospective study of consecutive patients.The purpose of this study was to
      compare the clinical effect of biomimetic mineralized collagen (MC) modified
      polymethylmethacrylate (PMMA) bone cement and traditional PMMA bone cement for
      the treatment of osteoporotic vertebral compression fractures (OVCF).New fracture
      on adjacent level is the major postoperative complication of percutaneous
      vertebroplasty (PVP). The clinical incidence was 12.4% to 27.7%. The increased
      stiffness of the treated vertebral body caused by filling bone cement is
      considered as one of the main reasons.A total of 30 patients treated with
      traditional PMMA bone cement from June 2013 to March 2016 were selected as the
      traditional group, while 50 patients treated with MC modified PMMA bone cement
      from July 2014 to March 2016 were selected as the modified group. The 2 groups
      were compared by injection time of the bone cements, postoperative pain relief
      effects, vertebral height restoration, CT value changes of the treated vertebral
      bodies, and postoperative complications in the clinical observations.The
      surgeries were successfully completed in both groups. In the treatment of OVCF,
      the MC modified bone cement was able to achieve the same pain relief and
      vertebral height restoration effects compared to traditional bone cement during
      the follow-ups, although the injection time of the cement was prolonged in the
      operation. MC modified bone cement significantly reduced the incidence of
      postoperative adjacent vertebral fracture from 13.3% to 2%, and significantly
      increased bone density of the treated vertebral bodies.The MC modified PMMA bone
      cement showed good clinical outcomes and better mechanical properties than the
      traditional bone cements.

PMID- 30212951
TI  - Effects of prophylactic oral ibuprofen on the closure rate of patent ductus
      arteriosus in premature infants.
AB  - The aim of this study was to investigate the effects of prophylactic oral
      ibuprofen on the closure rate of patent ductus arteriosus (PDA).This was a
      retrospective study and data on infants born before 36 weeks were collected. The
      prophylactic group was treated with ibuprofen (10, 5, and 5 mg/kg) from days 1 to
      3 after birth, respectively. The conventional group was treated with the same
      dose of ibuprofen from days 4 to 6 once they were echocardiographically confirmed
      with PDA on day 3 after birth. The placebo group was treated with 5% glucose.The
      closure rate of PDA in the prophylactic group significantly increased on day 7
      compared with the placebo group (P = .02), but showed no difference compared with
      the conventional group (P = .12). Serum NT-proBNP in the prophylactic and
      conventional groups decreased compared with the placebo group (P = .03 vs P =
      .07).Prophylactic oral ibuprofen can increase the closure rate of PDA in
      premature infants; however, it showed no significant advantages compared with
      conventional treatment. Serum NT-proBNP can be used to observe PDA treatment
      responses in premature infants.

PMID- 30212952
TI  - Robot-assisted radical prostatectomy may induce inguinal hernia within the first
      2 years: An 11-year single-surgeon experience of >400 cases.
AB  - At present, robot-assisted radical prostatectomy (RARP) is a gold standard in
      radical prostatectomy. The aim of this study was to evaluate the incidence, risk
      factors, and timing of occurrence of inguinal hernia (IH) after RARP.We included
      427 patients with prostate cancer who underwent RARP by a single surgeon from
      February 2006 to August 2017. Incidence, clinical, and pathological factors were
      investigated to assess relationship with the development of IH.Postoperative IH
      occurred in 29 cases (6.79% of all RARP patients), whereas 22 cases (75.9% of all
      IH patients) occurred within the first 2 years. The median follow-up period was
      5.2 years, and the median age of patients was 65 years. Postoperative IH
      occurrence was significantly associated with body mass index (BMI), smoking
      history, and low surgeon experience (P = .036, .023, and .048, respectively).
      However, low surgeon experience did not reach statistical significance after
      multivariate analysis.The overall incidence of IH after RARP was significantly
      associated with BMI and smoking history. With obvious incidence of IH within the
      first 2 years after operation which was not observed at the open prostatectomy,
      RARP itself may play a role in the development of IH.

PMID- 30212953
TI  - Bilateral sciatic neuropathy with severe rhabdomyolysis following venlafaxine
      overdose: A case report.
AB  - RATIONALE: Venlafaxine is an antidepressant and anxiolytic agent that functions
      by inhibiting central serotonin and norepinephrine reuptake, and it is a
      relatively recently introduced drug. In particular, overdose of venlafaxine has
      been reported to cause severe cardiac toxicity including ventricular tachycardia,
      prolongation of QT interval, and seizure or severe muscular injury. However,
      reports describing venlafaxine-induced rhabdomyolysis with neuropathy remain
      scarce. Accordingly, we report such a case involving a 49-year-old woman with
      bilateral sciatic neuropathy combined with rhabdomyolysis following venlafaxine
      overdose. PATIENT CONCERNS: The patient complained of severe pain and tenderness
      in both thighs, weakness in both ankle flexor and extensor muscles, and a
      tingling sensation in the toes of both feet. DIAGNOSES: Bilateral sciatic
      neuropathy combined with rhabdomyolysis following venlafaxine overdose.
      INTERVENTION: Needle electromyography revealed fibrillation potentials and
      positive sharp waves, with absent recruitment in all the major muscles
      innervating the sciatic nerve bilaterally. Pelvic magnetic resonance imaging was
      performed after electromyography and revealed multifocal enhancement of signal
      intensity, suggesting muscle necrosis in the gluteus and thigh muscles, and
      swelling of both sciatic nerves on short tau inversion recovery (STIR) imaging
      sequences. OUTCOMES: Two months later, the patient's ankle dorsiflexion strength,
      measured with manual muscle test, was grade 0/0, and ankle plantar flexion was
      grade 0/0. The patient reported little sensation at the lateral and posterior
      aspects of her lower leg, and dorsum and sole of the foot. A follow-up
      electromyography study revealed improvement in the long head of the right biceps
      femoris; polyphasic motor unit action potentials with diminished recruitment were
      observed, but otherwise unchanged. LESSONS: When encountering patients who have
      overdosed on venlafaxine, it is very important to detect and treat severe
      complications such as cardiac toxicity, seizure, and rhabdomyolysis, among
      others. However, if rhabdomyolysis has already materialized, it should not be
      forgotten that the secondary damage caused by it. Physicians should rapidly
      detect and be minimized to mitigate future complications.

PMID- 30212954
TI  - The risk factors of miscarriage and obstetrical outcomes of intrauterine normal
      pregnancy following heterotopic pregnancy management.
AB  - To investigate the clinical characteristics and risk factors for miscarriage of
      intrauterine normal pregnancy of patients with a heterotopic pregnancy (HP) after
      treatment.This was a retrospective study of medical records from CHA Bundang
      Medical Center. Sixty-four patients who were diagnosed with a HP between February
      2006 and July 2017 were included in this study. All analyses were performed using
      SAS software, version 9.4 (SAS Institute, Inc., Cary, NC). P values < .05 were
      considered statistically significant.Forty-eight patients had tubal ectopic
      pregnancies (EP), 10 patients had cornual EPs, 1 patient had a cesarean section
      scar EP, 4 patients had an ovarian EP, and 1 patient had bilateral tubal EP.
      Among the 64 patients, 14.1% (9/64) miscarried before 10 weeks of gestation after
      management. Mean gestational age (GA) at treatment was 5.97 +/- 0.50 weeks and
      6.80 +/- 1.04 weeks for miscarriage and nonmiscarriage group, respectively (P =
      .008). Significant differences were observed between 2 groups in terms of
      ultrasonographic features at the time HP was diagnosed (P = .040) Logistic
      regression models indicated that gestational age at treatment showed significant
      differences between 2 groups (OR: 0.003, 95% CI: 0.001-0.604).Immediate
      management after diagnosis could expect favorable prognosis of HP. GA at
      treatment was the only independent risk factor for miscarriage in patients with
      HP regardless of treatment methods.

PMID- 30212955
TI  - Fondaparinux in a critically Ill patient with heparin-induced thrombocytopenia: A
      case report.
AB  - RATIONALE: Fondaparinux, as a factor Xa-inhibitor, is used off label to manage
      heparin-induced thrombocytopenia (HIT), but little experience with HIT patients
      has been reported in the literature. Moreover, the use of fondaparinux for full
      anticoagulation in critically ill patients with HIT and renal insufficiency is
      limited. PATIENT CONCERNS: A trauma patient, who had received low molecular
      weight heparin (LMWH) and heparin to treat venous thromboembolism, developed
      thrombocytopenia and multiple organ dysfunction in the intensive care unit (ICU).
      Also, her deep venous thromboembolism (DVT) continued to progress. DIAGNOSIS: The
      final diagnosis was HIT. INTERVENTIONS: Fondaparinux was temporarily used for
      anticoagulation treatment of DVT for 7 days when another anticoagulant
      (argatroban) was unavailable. Although the patient had kidney dysfunction, a full
      therapeutic dose of 7.5 mg fondaparinux was administered every morning through
      subcutaneous injection for consecutive 7 days. OUTCOMES: The patient's
      thrombocytopenia and thrombosis were successfully treated without bleeding
      complications during therapeutic fondaparinux administration. LESSONS: This is
      the first case reporting the successful use of fondaparinux for full
      anticoagulation for DVT in a critically ill patient with HIT and renal
      insufficiency. Our experience suggests that fondaparinux might be an alternative
      for anticoagulation treatment in patients with HIT and kidney dysfunction if
      another anticoagulant (argatroban) is unavailable.

PMID- 30212956
TI  - Evaluation of nephroprotection of silymarin on contrast-induced nephropathy in
      liver cirrhosis patients: A population-based cohort study.
AB  - Recent findings from an animal experiment suggest a modest association between
      silymarin and decreased risk of contrast-induced nephropathy. However, the
      relationship between silymarin and contrast-induced nephropathy in patients with
      liver cirrhosis remains unclear.From 1997 to 2007, we identified 3019 patients
      with liver cirrhosis who were administered silymarin and matched them with 3019
      patients with liver cirrhosis who were not administered silymarin. Each patient
      was followed up for a minimum of 4 years. After adjusting for age, gender,
      hepatitis B, hepatitis C, alcoholic hepatitis, and Charlson comorbidity index, we
      considered death occurrence and used the Fine and Gray regression models to
      calculate subdistribution hazard ratios (sHRs) for contrast-induced nephropathy.
      Sensitivity analyses were also performed using the same model on the subgroups
      classified by comorbidity.Using the Fine and Gray regression models and with
      death as the competing risk, we observed that sHR for contrast-induced
      nephropathy was 0.94-fold higher in the silymarin cohort than in the nonsilymarin
      cohort (95% confidence interval = 0.61-1.47, P = .791). On the basis of
      sensitivity analyses results classified by comorbidity, a nonsignificant decrease
      in risk of contrast-induced nephropathy was found.Silymarin shows no nephron
      protective positive effects on contrast-induced nephropathy. Silymarin did not
      play a nephron-protective role according to Longitudinal Health Insurance
      Database of Taiwan. Clinical trials are necessary to further assess the nephron
      protective effects of silymarin of contrast-induced nephropathy.

PMID- 30212957
TI  - Association between oral health and colorectal adenoma in a screening population.
AB  - Although periodontal disease and gastrointestinal tract health are closely
      associated, few studies have investigated whether periodontitis is a risk factor
      for colorectal adenoma. The aim of this study was to investigate whether there is
      an association between periodontitis and the risk of colorectal adenoma in
      asymptomatic healthy people.From January 2013 to October 2015, we retrospectively
      enrolled 42,871 patients who underwent health screening at Kangbuk Samsung
      Hospital in South Korea. Demographic and clinical data were collected before
      colonoscopy. We calculated the odds ratio (OR) for adenoma in these patients.The
      median age was 39.3 +/- 8.7 years and 70.4% of the patients were men; 32.5% had a
      body mass index (BMI) 25.0 kg/m. The frequency of adenoma was 12% (n = 5136). A
      higher risk of adenoma was associated with the following factors: BMI 25.0 kg/m
      (OR 1.51, 95% confidence interval [CI]: 1.42-1.61), current smoker (OR 1.51, 95%
      CI: 1.42-1.61), former smoker (OR 1.28, 95% CI: 1.19-1.37), periodontitis (OR
      1.95, 95% CI: 1.82-2.0), moderate alcohol intake (OR 1.8, 95% CI: 1.69-1.93), and
      heavy alcohol intake (OR 2.67, 95% CI: 2.24-3.18).Being male or a former or
      current smoker, alcohol intake above the moderate level, and periodontitis
      increase the risk of colorectal adenoma. These findings suggest that controlling
      oral disease is important to the prevention and management of colorectal adenoma.
      The findings of this study could be applied to risk stratification and colorectal
      cancer prevention programs, including screening guidelines.

PMID- 30212958
TI  - Texture analysis of magnetic resonance T1 mapping with dilated cardiomyopathy: A
      machine learning approach.
AB  - The diagnosis of dilated cardiomyopathy (DCM) remains a challenge in clinical
      radiology. This study aimed to investigate whether texture analysis (TA)
      parameters on magnetic resonance T1 mapping can be helpful for the diagnosis of
      DCM.A total of 50 DCM cases were retrospectively screened and 24 healthy controls
      were prospectively recruited between March 2015 and July 2017. T1 maps were
      acquired using the Modified Look-Locker Inversion Recovery (MOLLI) sequence at a
      3.0 T MR scanner. The endocardium and epicardium were drawn on the short-axis
      slices of the T1 maps by an experienced radiologist. Twelve histogram parameters
      and 5 gray-level co-occurrence matrix (GLCM) features were extracted during the
      TA. Differences in texture features between DCM patients and healthy controls
      were evaluated by t test. Support vector machine (SVM) was used to calculate the
      diagnostic accuracy of those texture parameters.Most histogram features were
      higher in the DCM group when compared to healthy controls, and 9 of these had
      significant differences between the DCM group and healthy controls. In terms of
      GLCM features, energy, correlation, and homogeneity were higher in the DCM group,
      when compared with healthy controls. In addition, entropy and contrast were lower
      in the DCM group. Moreover, entropy, contrast, and homogeneity had significant
      differences between these 2 groups. The diagnostic accuracy when using the SVM
      classifier with all these histogram and GLCM features was 0.85 +/- 0.07.A
      computer-based TA and machine learning approach of T1 mapping can provide an
      objective tool for the diagnosis of DCM.

PMID- 30212959
TI  - Testing the neutral theory of biodiversity with the microbiome dataset from
      cystic fibrosis patients.
AB  - Cystic fibrosis (CF) is a hereditary disease that is characterized by defective
      mucociliary clearance, airway obstruction, chronic infection, and persistent
      inflammation. Cystic fibrosis pulmonary exacerbation (CFPE) majorly causes the
      morbidity of CF patients. Although CF has been demonstrated to change the
      composition of lung microbial community, previous studies have not made efforts
      to study the differences in the mechanism of assembly and diversity maintenance
      of lung microbial community in CF patients. In this study, we applied the neutral
      theory of biodiversity to comparatively investigate the assembly and diversity
      maintenance of the lung microbial community before and after the antibiotic
      treatment by reanalyzing the dataset from Fodor et al's study. We found that no
      one sample in the lung microbial communities of the sputum samples of
      Exacerbation group, nor those of End-of-treatment group satisfied the predictions
      of neutral model, suggesting that the neutral-process does not dominate in CF
      patients before and after antibiotic treatments. By comparing the biodiversity
      parameter between Exacerbation and End-of-treatment group, we found that the
      former had the significantly higher biodiversity, but the change in diversity
      parameter is slight and the P value is close to.05 (P value = .41). Therefore,
      our second finding is that although CFPE may increase the biodiversity of lung
      microbial community, the change is not essential.

PMID- 30212960
TI  - Accuracy of objective parameters in acute epiglottitis diagnosis: A case-control
      study.
AB  - Lateral neck radiography is often used as a screening tool in emergency
      departments for suspected acute epiglottitis. The qualitative radiographic signs
      have been mainly used. The aim of this study was to evaluate the accuracy of
      objective radiographic parameters to aid diagnosis of acute epiglottitis.Patients
      who were diagnosed with acute epiglottitis from January 2006 to December 2016
      were included in this case-control study. Control subjects with normal lateral
      neck radiograph findings were included at a 1:4 ratio during the same period. The
      clinical findings of the patients were assessed from electronic medical records
      and radiographs were interpreted by a board-certified radiologist and a board
      certified emergency medicine physician. The widths of the 3rd cervical vertebral
      body, epiglottis base (EWB), epiglottis tip (EWT), aryepiglottic fold (AFW), and
      hypopharynx, as well as the dimensions of the retropharyngeal and retrotracheal
      soft tissues, were retrospectively measured. The sensitivity, specificity, and
      receiver operating characteristic (ROC) curves were analyzed for the measured
      parameters, and cutoff values were determined to predict acute epiglottitis. The
      predictive cutoff values of radiologic parameters were evaluated using 5-fold
      cross-validation.A total 260 epiglottitis patients and 1166 controls were
      included in the study. In the ROC curve analysis, the EWB had an area under the
      ROC curve (AUROC) of 0.99 for a cutoff value of 5.02 mm (sensitivity, 96.2%;
      specificity, 98.2%). The EWT had an AUROC of 0.97 for a cutoff value of 4.84 mm
      (sensitivity, 91.2%; specificity, 97.3%). The AFW had an AUROC of 0.88 for a
      cutoff value of 6.59 mm (sensitivity, 86.5%; specificity, 78.8%). The 5-fold
      cross-validation achieved AUROCs of 0.97 for EWB, 0.94 for EWT, and 0.83 for
      AFW.The objective radiographic parameters in lateral neck radiography may be
      useful in diagnosing acute epiglottitis. Further prospective studies may be
      warranted to evaluate the diagnostic performance in actual clinical practice.

PMID- 30212961
TI  - Efficacy of diode-emitting diode (LED) photobiomodulation in pain management,
      facial edema, trismus, and quality of life after extraction of retained lower
      third molars: A randomized, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: In dentistry, one of the most common surgical procedures is the
      removal of retained third molars. This surgery generates great morbidity to the
      participants for causing pain, edema, and trismus due to surgical trauma. The
      objective of the present study is to evaluate the efficacy of photobiomodulation
      with light emitting diode (LED) in the control of pain, facial edema, trismus,
      and quality of life resulting from the extraction of retained lower third molars.
      METHODS: A randomized, double-blind, placebo-controlled clinical trial involving
      38 adult participants, who meet the criteria of eligibility and agree to
      participate in the study. Before the surgeries are performed, the facial and
      mouth opening measures of all the participants will be taken. Immediately after
      the surgeries, participants will be randomized into 2 groups. In the LED group,
      participants will receive LED applications (intra oral with 660 nm, 12J and
      extraoral with 850 nm, 108J) in the immediate postoperative, first and second
      days after the surgical procedure. In the control group, the participants will be
      attended in the same way as in the LED group, however, the person in charge of
      the application will simulate the irradiation. Pain (EVA and NRS-101),
      postoperative edema, trismus, temperature, dysphagia, and hematoma will be
      evaluated after 1, 2, 5, and 7 days. The oral health impact profile (OHIP-14
      Questionnaire) and anxiety analysis (Beck anxiety inventory -BAI) questionnaires
      will be applied preoperatively and 7 days after treatment. The appropriate
      statistical tests will be applied for each specific analysis in a significance
      level of 5%. DISCUSSION: Although the use of low-power laser in the postoperative
      has shown good results in the control of postoperative sequelae, this is the
      first study on the efficacy of the use of LED in this situation.

PMID- 30212962
TI  - Risk-adjusted outcomes of inpatient medicare medical admissions.
AB  - It is important that actual outcomes of care and not surrogate markers, such as
      process measures, be used to evaluate the quality of inpatient care. Because of
      the heterogenous composition of patients, risk-adjustment is essential for the
      objective evaluation of outcomes following inpatient care. Comparative evaluation
      of risk-adjusted outcomes can be used to identify suboptimal performance and can
      provide direction for care improvement initiatives.We studied the risk-adjusted
      outcomes of 6 medical conditions during the inpatient and 90-day post-discharge
      period to identify the opportunities for care improvement. The Medicare Limited
      Dataset for 2012 to 2014 was used to identify acute myocardial infarction (AMI),
      chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF),
      pneumonia (PNEU), cerebrovascular accidents (CVA), and gastrointestinal
      hemorrhage (GIH). Stepwise logistic predictive models were developed for the
      adverse outcomes (AOs) of inpatient deaths, 3-sigma prolonged length-of-stay
      outliers, 90-day post-discharge deaths, and 90-day readmissions after unrelated
      events were excluded. Observed and predicted AOs were determined for each
      hospital with >=75 cases for each of the 6 medical conditions. Z-scores and risk
      adjusted AO rates for each hospital permitted comparative analysis of outcomes
      after adjusting for covariance among the medical conditions.There were a total of
      1,811,749 patients from 973 acute care hospitals with the 6 medical conditions. A
      total of 41% of all patients had >=1 AO events. One or more readmissions were
      identified in 29.8% of patients. A total of 64 hospitals (6.4%) were 2 standard
      deviations better than the mean for risk-adjusted outcomes, and 72 (7.4%) were 2
      standard deviations poorer. The best performing decile of hospitals had mean AO
      rates of 35.1% (odds ratio = 0.766; 95% confidence interval (CI) CI: 0.762-0.771)
      and the poorest performing decile a mean AO rate of 48.5% (odds ratio = 1.357;
      95% CI: 1.346-1.369). Volume of qualifying cases ranged from 670 to 9314; no
      association was identified for increased volume of patients (P < .40).Risk
      adjusted AO rates demonstrated nearly a 14% opportunity for care improvement
      between top and suboptimal performing hospitals. Hospitals must be able to
      benchmark objective measurement of outcomes to inform quality initiatives.

PMID- 30212964
TI  - Brain metastasis of choriocarcinoma presenting as multiple intracranial
      hematomas: A case report.
AB  - RATIONALE: Choriocarcinoma is the most malignant type of gestational
      trophoblastic neoplasia. Brain metastasis is the main cause of death and
      disability in choriocarc- inoma patients. Brain metastasis of choriocarcinoma
      easily invades the vessel wall to form microaneurysms, so we have reason to
      believe that multiple intracerebral hemorrhage is related to neoplastic
      intracranial microaneurysms. PATIENT CONCERNS: We report a rare case of brain
      metastasis of choriocarcinoma that caused six hemorrhages in four lesions within
      50 days and anterior cerebral artery aneurysm. DIAGNOSES: We diagnosed multiple
      intracerebral hematoma, choriocarcinoma and intracranial aneurysms.
      INTERVENTIONS: Evacuation of hematoma by craniotomy. OUTCOMES: The patient
      finally asked to terminate the treatment and was discharged. One month later, the
      patient died of upper gastrointestinal bleeding. LESSONS: more than 20 cases of
      oncotic aneurysm from choriocarcinoma have been reported in the English
      literature, but few had multiple hematomas. Therefore, this case is unique. Brain
      metastasis of choriocarcinoma should be considered when patients experience
      unexplained cerebral hemorrhage, especially repeated intracranial hemorrhage in
      women of childbearing age. Early and intensive treatment can help achieve a
      better prognosis and avoid a fatal outcome. Multiple intracranial hematomas are
      related to neoplastic intracranial microaneurysms.

PMID- 30212963
TI  - Omega-3 polyunsaturated fatty acid supplementation and non-alcoholic fatty liver
      disease: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Clinical trials examining the therapeutic benefit of omega-3
      polyunsaturated fatty acids (omega-3 PUFAs) on nonalcoholic fatty liver disease
      (NAFLD) have reported inconsistent results. We performed a meta-analysis of
      randomized controlled trials (RCTs) examining the effect of omega-3 PUFA
      supplementation on NAFLD, and provide substantial evidence on whether omega-3
      PUFA supplementation has a favorable effect for treating NAFLD. METHODS: We
      searched the PubMed, Cochrane Library, Springer Link, China National Knowledge
      Infrastructure (CNKI), Wanfang, and Chinese Scientific and Technological Journal
      (VIP) databases for RCTs on oral omega-3 PUFA supplementation in patients with
      NAFLD. The data were pooled; meta-analyses were conducted using random-effect or
      fixed-effect models. RESULTS: Eighteen studies involving 1424 patients were
      included. We found a significant benefit for omega-3 PUFAs vs control for liver
      fat, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl
      transferase, triglycerides, insulin resistance, and glucose. However, there was
      significant interstudy heterogeneity. Subgroup and regression analyses showed no
      significantly clear methodologic discrepancy. Publication bias and serious
      adverse events were not detected. CONCLUSIONS: Our meta-analysis suggests that
      omega-3 PUFA supplementation may decrease liver fat and hepatic enzyme
      parameters. However, more large-scale, well-designed RCTs are needed to confirm
      the effect of omega-3 PUFA supplementation on these parameters.

PMID- 30212965
TI  - Relationship between skeletal muscle mass and lung function in Korean adults
      without clinically apparent lung disease.
AB  - Previous studies have demonstrated that low skeletal muscle mass is related to
      decreased lung function in patients with chronic obstructive pulmonary disease.
      However, there is little information about the relationship between skeletal
      muscle mass and lung function in asymptomatic adults without clinically apparent
      lung disease.This was a cross-sectional study of 240,562 Korean adults without
      known lung disease. All subjects underwent both pulmonary function test (PFT) and
      bioelectrical impedance analysis in the health checkup program at Kangbuk Samsung
      Hospital. Skeletal muscle mass index (SMI) was estimated as skeletal muscle
      mass/weight*100. We analyzed the relationship between SMI and PFT using
      multivariate logistic regression models.Of the 240,562 study subjects, values for
      forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and
      peak expiratory flow (PEF) were decreased across quartiles (Qs) of decreasing
      SMI. After adjustments for various confounders including demographic and health
      behavior-related factors, odds ratios (ORs; 95% confidence interval) for subjects
      with FVC% <80% for Q1-Q3 compared with Q4 (reference) were 2.97 (2.74-3.17), 2.11
      (1.99-2.27), and 1.66 (1.52-1.83), respectively. ORs for subjects with FEV1% <80%
      for Q1-Q3 compared with Q4 were 2.64 (2.43-2.83), 1.96 (1.83-2.09), and 1.51
      (1.43-1.62), respectively. Lastly, OR for subjects with PEF% <80% for Q1-Q3
      compared with Q4 were 1.73 (1.58-1.89), 1.35 (1.26-1.45), and 1.23 (1.15-1.30),
      individually. Subgroup analyses for gender and all age groups showed the
      associations of decreasing SMI Qs with lower FVC%, FEV1%, and PEF% remained
      significant.Decreased SMI was independently associated with decline in lung
      function in apparently healthy adults. This association was sustained in subgroup
      analyses by gender and all age groups.

PMID- 30212966
TI  - Associations of the risk of lung cancer with serum 25-hydroxyvitamin D level and
      dietary vitamin D intake: A dose-response PRISMA meta-analysis.
AB  - The associations of the risk of lung cancer with the vitamin D intake and serum
      level are controversial. We performed a comprehensive dose-response meta-analysis
      to evaluate the precise relationships between the above mentioned parameters.We
      performed a web search of the PubMed, Medline, and Embase databases to identify
      potential studies that evaluated the relationships between vitamin D intake or
      serum 25-hydroxyvitamin D (25([OH]D) levels and the risk of lung cancer on
      December 5, 2017. According to the inclusion and exclusive criteria, 16 studies
      were included in this meta-analysis. The pooled relative risks (RRs) with 95%
      confidence intervals (CIs) were used to assess the strength of the associations.
      A dose-response analysis was conducted to quantitate the relationship between the
      serum 25(OH)D or vitamin D intake and the risk of lung cancer.The pooled RR
      (highest level vs lowest level) showed that the serum 25(OH)D level was not
      associated with the risk of lung cancer (RR = 1.046, 95% CI = 0.945-1.159). A
      high vitamin D intake was inversely correlated with the lung cancer risk (RR =
      0.854, 95% CI = 0.741-0.984). No significant dose-response relationship was
      observed between the serum 25(OH)D level and the lung cancer risk. The linearity
      model of the dose-response analysis indicated that with every 100 IU/day increase
      in vitamin D intake, the risk of lung cancer decreased by 2.4% (RR = 0.976, 95%
      CI = 0.957-0.995, P = .018).A high vitamin D intake provides limited protection
      against lung cancer carcinogenesis.

PMID- 30212967
TI  - A novel 55-basepair deletion of hydroxymethylbilane synthase gene found in a
      Chinese patient with acute intermittent porphyria and her family: A case report.
AB  - RATIONALE: Acute intermittent porphyria (AIP) is caused by hydroxymethylbilane
      synthase (HMBS) gene mutation. PATIENT CONCERNS: A Chinese female patient with
      very typical AIP symptoms of severe abdominal pain, seizures, hypertension, and
      tachycardia, accompanied with hyponatremia, anemia, and hyperbilirubinemia.
      DIAGNOSES: She was diagnosed as AIP based on positive result of urine
      porphobilinogen and her clinical syndrome. INTERVENTIONS: The proband was treated
      with intravenous glucose (at least 250 g per day) for 4 days. HMBS mutation was
      investigated in this family by Sanger sequencing. OUTCOMES: A heterozygous
      mutation of the HMBS gene was identified in the proband and 7 other family
      members. Genetic sequencing showed a deletion of 55 basepairs
      (C.1078_1132delGCCCATTAACTGGTTTGTGGGGCACAGATGCCTGGGTTGCTGCTGTCCAGTGCCT) including
      the stop codon position, leading to frameshift mutation. The mutation has not
      been documented in current gene databases. Further prediction of mutated protein
      structure suggests that the mutation is likely to produce prolonged peptide with
      structural change and less stability. LESSONS: Physicians should pay attention to
      AIP attack in patients with suspected symptoms and make use of genetic testing to
      increase identification of mutated HMBS gene carriers for further preventive
      strategy.

PMID- 30212968
TI  - Prognostic impact of preoperative anemia on upper tract urothelial carcinoma.
AB  - The aim of this study was to investigate the effect of preoperative anemia on the
      prognosis of patients who underwent radical nephroureterectomy (RNU) for upper
      tract urothelial carcinoma (UTUC).A total of 620 patients with UTUC were
      retrospectively analyzed. Anemia was decided by preoperatively measured
      hemoglobin values based on the World Health Organization (WHO) classification.
      Kaplan-Meier method and Cox proportional hazards regression models were used to
      analyze the relationship between anemia and survival outcomes. The meta-analysis
      part was performed according to PRISMA guidelines.The median follow-up was 51
      (range: 1-168) months. A total of 246 patients had preoperative anemia in our
      cohort. Anemia was found to be related to high-grade (P < .001), sessile
      architecture (P = .001), advanced T stage (P < .001), lymphovascular invasion
      (LVI) (P = .006), and worse chronic kidney disease (CKD) stage (P = .012). Kaplan
      Meier curves revealed that patients with preoperative anemia had worse overall
      survival (OS), cancer-specific survival (CSS), and disease recurrence-free
      survival (RFS) (all P < .001). Multivariable Cox analyses found that anemia was
      an independent predictor of CSS [hazard ratio (HR) 1.719, 95% confidence interval
      (95% CI): 1.285-2.300], RFS (HR 1.427, 95% CI: 1.114-1.829) and OS (HR 1.756, 95%
      CI: 1.353-2.279). Among patients without end-stage renal disease (ESRD, n = 614),
      the anemia was also proved to be associated with worse outcomes in multivariable
      Cox analysis (OS, HR 1.759, 95% CI: 1.353-2.287; CSS, HR 1.726, 95% CI: 1.289
      2.311, and RFS, HR 1.431, 95% CI: 1.117-1.837). Seven studies were included in
      the meta-analysis, and the pooled results showed that anemia was also related to
      worse CSS (HR 2.05, 95% CI: 1.73-2.44), RFS (HR 1.57, 95% CI: 1.30-1.90), and OS
      (HR 1.53, 95% CI: 1.10-2.13), but not related to intravesical recurrence (HR
      1.17, 95% CI: 0.75-1.82).Preoperative anemia was proved to be significantly
      associated with worse oncologic outcomes in patients with UTUC following RNU.

PMID- 30212969
TI  - Comedication with interacting drugs predisposes amiodarone users in cardiac and
      surgical intensive care units to acute liver injury: A retrospective analysis.
AB  - Risk factors and underlying mechanisms for liver injury associated with
      amiodarone remain elusive. This study aimed to investigate the drug-related
      covariates for acute liver injury by amiodarone-an intriguing compound of high
      lipophilicity, with a long half-life and notable efficacy.The medical, pharmacy,
      and laboratory records of new amiodarone users admitted to the cardiac or
      surgical intensive care units of a medical center were examined retrospectively.
      A Cox regression model with time-varying dose-related variables of amiodarone was
      utilized to estimate the hazard ratio (HR) of amiodarone-associated liver injury
      while adjusting for concomitant therapy and relevant covariates.Of the 131
      eligible patients among 6,572 amiodarone users (46,402 prescriptions), 6 were
      identified as amiodarone-associated liver injury cases. In comparison to controls
      (n = 125), this liver injury cohort (n = 6) had significantly higher numbers of
      amiodarone-interacting (2.7 +/- 2.0 vs 0.9 +/- 0.9 drugs, P = .02) and
      hepatotoxic (3.8 +/- 0.8 vs 2.5 +/- 1.7 drugs, P = .03) comedications. The number
      of comedications with amiodarone-interacting potential (HR 2.07, 95% confidence
      interval [CI] 1.02-4.22, P = .04) and amiodarone cumulative doses standardized by
      body surface area (HR 6.82, 95% CI 1.72-27.04, P = .01) were independent risk
      factors for liver injury associated with amiodarone.Drug-related (amiodarone
      cumulative dose, interacting drugs) factors were significant predictors of
      amiodarone-associated acute liver injury. A prudent evaluation of each medication
      profile is warranted to attain precision medicine at the level of patient care,
      especially for those treated by medications with complex physicochemical and
      pharmacokinetic properties, such as amiodarone.

PMID- 30212970
TI  - 11C-acetate and 18F-fluorodeoxyglucose positron emission tomography/computed
      tomography dual imaging for the prediction of response and prognosis after
      transarterial chemoembolization.
AB  - The aim of the present study was to evaluate the clinical significance of dual
      radiotracer studies, C-acetate and F-fluoro-D-glucose positron emission
      tomography/computed tomography (F-FDG PET/CT), for the prediction of response and
      recurrence after transarterial chemoembolization (TACE).This study
      retrospectively included a total 42 hepatoceullar carcinoma (HCC) patients
      (median age, 59; range, 34-85 years old) who underwent C-acetate and F-FDG PET/CT
      concurrently. Tumor uptake normalized by liver uptake (TNR; maximum tumor SUV to
      mean normal liver SUV ratio) was obtained first. Then, FAratio, which is the
      ratio of F-FDG TNR (TNR_FDG) to C-acetate TNR, was obtained and correlated with
      response after TACE and recurrence-free survival (RFS), using a Cox multivariate
      proportional-hazard model.Among clinical factors, including the Hepatoma Arterial
      Embolization Prognostic score and positron emission tomography (PET) parameters,
      multiple regression analysis revealed FAratio and tumor size to be the only
      significant factors. As a PET parameter, FAratio exhibited the largest area under
      the curve in the prediction of response after TACE. In the Cox multivariate
      proportional-hazard model, TNR_FDG was the only significant predictive factor for
      RFS. In subgroup analysis, TNR_FDG was the only significant predictive factor for
      recurrence in intermediate stage patients. However, FAratio was the only
      significant predictive factor for recurrence in advanced stage patients.Dual
      radiotracer use of C-acetate and F-FDG PET/CT contributed to the prediction of
      response and recurrence after TACE. Used in addition to F-FDG, C-acetate PET/CT
      could give additional information in advanced stage patients. Based on the
      characteristics of tumor metabolism assessed by dual radiotracer PET/CT,
      treatment plans could be more personalized and optimized.

PMID- 30212971
TI  - An account of data entry inconsistencies and their impact on positron emission
      tomography quantification.
AB  - Reproducibility is essential to clinical application of positron emission
      tomography (PET) quantification. Human lapses in data registration and protocol
      compliance are pervasive sources of intrasite quantification variability.
      Although rarely assessed or reported, these lapses are ultimately a limitation to
      harmonization in multicenter clinical trials. A comprehensive account of their
      possible extent is relayed here.This is a retrospective audit of errors in manual
      registration of study parameters and in protocol adherence across a sample of in
      center research projects over one year (201 patients, 222 PET/CT scans).
      Discrepancies in patient height and weight; tracer type; dose; injection; and
      scan times were listed. Correspondent variances in standardized uptake values
      (SUVs) normalized by body weight, SUV (BW), and body surface area, SUV (BSA),
      were assessed.Manual misregistrations totalled 41.8%. These were mainly small,
      but with a few large deviations, and most significant in weight (range: -1-100
      kg) and dose (-19 to 12 MBq). Errors were more frequent and generally larger in
      non-routine studies. This also applied to protocol compliance. A 50.7%
      noncompliance was found with significant deviations in dose (-106 to 208 MBq) and
      especially in early scan uptake times (-37 to 54 min). Although misregistrations
      did not overall translate into significant SUV variability, noncompliance did.
      These errors contributed a factor 0.02 to 1.45 and 0.71 to 3.09 SUV (BW) change,
      respectively. SUV (BSA) saw a significant 21% to 22% decrease with mistyped
      height and weight.Inconsistency was frequent but less prominent in data entry
      than in protocol compliance. As both caused some substantial SUV variances, intra
      site assessments and data checking are required for clinical trials.

PMID- 30212972
TI  - Anatomical feasibility study of unilateral percutaneous kyphoplasty for lumbar
      through the conventional transpedicular approach: An observational study using 3D
      CT analysis.
AB  - The aim of the study was to discuss the significance of sex, level, age, and side
      in relation to the anatomical distinctions of unilateral percutaneous kyphoplasty
      (PKP) for lumbar osteoporotic vertebral compression fractures (OVCFs) through the
      conventional transpedicle approach (CTPA).We have retrospectively collected
      lumbar spines (L1-L5) of 200 patients and simulated PKP on the 3D CT scans
      through unilateral CTPA. We have measured the distance between the entry point
      and the midline of the vertebral body (DEM), the puncture inclination angle
      (PIA), safe range of the inner inclination angles (SRA), and the success rate
      (SR) of puncture.Significant differences (P < .05) between the male and female
      for L1 to L5, left and right side for L1 to L3 in the mean DEM were shown. The
      DEM from L1 to L5 was significantly increased (P < .05) from (20.6 +/- 2.0) mm to
      (29.8 +/- 2.9) mm. For L1 to L5, the right maximum PIA was significantly larger
      than the left. The maximum PIA and SRA in the male was significantly larger than
      that in the female. The SRA from L1 to L5 was significantly increased (P < .05)
      from (19.5 +/- 5.9) degrees  to (48.9 +/- 8.1) degrees . The SR in male was
      significantly higher than that in female for L1 to L4. There were no significant
      differences in the SR between different age groups except for L4. The SR from L1
      to L5 was significantly increased (P < .05) from 26.3% to 99.0%.DEM was 20.6 to
      29.8 mm according to different levels. The value of DEM, PIA, SRA, and SR was
      significantly increased from L1 to L5. No significant differences in the SR
      between right and left for L1 to L5, different age groups except for L4 were
      observed.

PMID- 30212973
TI  - Fluoroscopic guidance biopsy for severe anastomotic stricture after
      esophagogastrostomy of esophageal carcinoma: A STROBE-compliant article.
AB  - To determine the safety and effectiveness of fluoroscopic guidance biopsy in the
      diagnosis of serve anastomotic stricture after esophagogastrostomy for esophageal
      carcinoma.A total of 55 patients with severe anastomotic stricture were enrolled
      for forceps biopsy between June 2013 and July 2017. Chest computed tomography
      (CT) and esophagogram were used to determine the location and extent of
      stricture. Specimens were collected from the site of stricture by using biopsy
      forceps under fluoroscopic guidance. Stooler's dysphagia score was compared
      before and after treatment.The technical success rate of fluoroscopic guidance
      biopsy was 100%, with no serious complications occurred. A total of 38 patients
      were diagnosed as benign stricture, of which, 2 patients were further diagnosed
      as cancer by further biopsy, with a missed diagnosis rate of 5.3%, and 1 patient
      developed squamous cell carcinoma after 5 months. Thus 20 cases were diagnosed as
      cancer, 3 cases were adenocarcinoma and 17 cases were squamous cell carcinoma.
      Balloon dilation was performed for 20 patients (33 times) of benign stricture,
      and 9 patients (10 times) of malignant stricture. A total of 26 esophageal
      covered stents were implanted for benign restenosis after repeated balloon
      dilation. A total of 8 esophageal covered stents were implanted for malignant
      stricture. After esophagus stenting, dysphagia was immediately alleviated. The
      dysphagia score decreased from 3.4 +/- 0.1 to 0.7 +/- 0.1 (P < .001) after
      treatment.Fluoroscopic guidance biopsy is a safe and effective procedure for
      directing appropriate treatment of anastomotic stricture after
      esophagogastrostomy, and it may be an alternative approach for patients who
      cannot tolerate fibergastroscopy.

PMID- 30212974
TI  - Association between the overexpression of Her3 and clinical pathology and
      prognosis of colorectal cancer: A meta-analysis.
AB  - BACKGROUND: This study aimed to investigate the association between the
      overexpression of human epidermal growth factor receptor-3 (Her3) and the
      clinicopathological parameters and survival of patients with colorectal cancer
      (CRC). METHODS: Relevant studies on the overexpression of Her3 (measured by
      immunohistochemistry) and overall survival (OS) in patients with CRC were
      searched for in PubMed, EMBASE, and Cochrane Library. Published data were
      extracted and computed into odds ratios (ORs) for assessing the association of
      Her3 overexpression with tumor differentiation, tumor node metastasis (TNM)
      stage, position of colon cancer, sex, and age. Prognostic data were computed into
      hazard ratios (HRs) for OS. RESULTS: Eight studies including 1716 patients with
      CRC were included in this meta-analysis. The results revealed a significant
      association between Her3 overexpression and tumor differentiation [OR = 2.38; 95%
      confidence interval (95% CI): 1.76-3.22; P < .001], TNM tumor stage (OR = 0.71;
      95% CI: 0.53-0.96; P = .03), and position of colon cancer (OR = 1.71; 95% CI:
      1.28-2.27; P < .001). While patients with Her3 overexpression demonstrated a
      worse tumor response (OR = 0.31; 95% CI: 0.16-0.60; P < .001) and OS after
      treatment with cetuximab (HR = 1.86; 95% CI: 1.24-2.79; P = .003), they
      demonstrated better OS after symptomatic treatment (HR = 0.65; 95% CI: 0.50-0.85;
      P = .002). Her3 overexpression was not associated with sex (OR = 1.03; 95% CI:
      0.83-1.28; P = .79), age (OR = 0.96; 95% CI: 0.75-1.24; P = .77), colon or rectum
      site (OR = 0.79; 95% CI: 0.44-1.43; P = .44), and total OS (HR = 1.09; 95% CI:
      0.69-1.72; P = .72). CONCLUSION: Her3 expression is associated with the clinical
      pathology and prognosis of CRC, which explains the nonefficacy of cetuximab
      treatment in patients with CRC.

PMID- 30212975
TI  - Comparison of 99mTc-methyl diphosphonate bone scintigraphy and 18F
      fluorodeoxyglucose positron emission tomography/computed tomography to predict
      histologic response to neoadjuvant chemotherapy in patients with osteosarcoma.
AB  - We compared the usefulness of Tc-methyl diphosphonate (Tc-MDP) bone scintigraphy
      and F-fluorodeoxyglucose (FDG) for positron emission tomography/computed
      tomography (PET/CT) in predicting histologic response in patients with
      osteosarcoma receiving neoadjuvant chemotherapy (NAC).We retrospectively reviewed
      62 patients with high-grade osteosarcoma who had received 2 cycles of NAC and
      surgery. All patients underwent Tc-MDP bone scintigraphy and F-FDG PET/CT before
      and after NAC. Tc-MDP uptake in the primary tumor was measured quantitatively as
      the maximum tumor-to-nontumor ratio (T/NTmax) and F-FDG uptake was measured as
      the maximum standardized uptake value (SUVmax), before and after NAC. The percent
      changes of T/NTmax (percent changes of the maximum tumor-to-nontumor ratio
      [Delta%T/NTmax]) and SUVmax (percent changes of the maximum standardized uptake
      value [Delta%SUVmax]) after NAC were calculated and the correlations between
      these parameters were evaluated. After surgery, the effects of NAC were graded
      histopathologically (good vs poor) and the optimum cut-off values of
      Delta%T/NTmax and Delta%SUVmax for predicting histologic response were assessed
      using the receiver operating characteristic (ROC) curve analysis.Delta%T/NTmax
      and Delta%SUVmax were positively correlated with each other (r = 0.494, P < .01).
      Based on the ROC curve analysis, both Delta%T/NTmax (area under the curve [AUC] =
      .772, P < .01) and Delta%SUVmax (AUC = .829, P < .01) predicted good histologic
      response. However, there was no significant difference between the AUCs of
      Delta%T/NTmax and Delta%SUVmax (P = .44). The sensitivity and specificity for
      predicting good histologic response were 83.3% and 75.0%, for the criterion
      Delta%T/NTmax <-12.5%, and 80.0% and 81.3% for the criterion Delta%SUVmax <
      49.0%, respectively.The Tc-MDP bone scan and F-FDG PET scan are non-inferior to
      each other in predicting the histologic response of osteosarcoma treatments. The
      Tc-MDP bone scan and F-FDG PET scan showed respective advantages with differing
      features. Therefore, physicians should consider which scan is appropriate for
      their own institute based on the advantages of each scan and the circumstances of
      the institute.

PMID- 30212976
TI  - The impact of informing diagnosis on quality of life in patients with cancer: A
      protocol of systematic review and meta-analysis.
AB  - BACKGROUND: Cancer is the second leading cause of death globally. More millions
      new cancer cases are diagnosed, and millions persons died due to cancer each
      year. There are different attitudes on disclosure of diagnosis to the patients
      with cancer. The current systematic reviews are qualitative, and indicate that
      there is limited evidence on the association between awareness of diagnosis and
      quality of life in patients with cancer. In this study, we aim to evaluate the
      effect of awareness of diagnosis on quality of life in patients with cancer by
      conducting a systematic review and meta-analysis. METHODS: We will perform a
      comprehensive electronic search in the databases below: MEDLINE (via PubMed),
      EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, WEB OF SCIENCE,
      Chinese Biomedical Literature database, WANFANG database, and China National
      Knowledge Infrastructure. The cohort studies focusing on the association between
      awareness of diagnosis and quality of life in patients with cancer will be
      included. The risk of bias for the included studies will be appraised using the
      Newcastle-Ottawa Scale tool for cohort study. We will pool the effect estimates
      from the included studies to quantitatively present the strength of the
      association of interest. RESULTS: This study will present pooled effect estimates
      regarding the impact of informing diagnosis on quality of life in patients with
      cancer. CONCLUSION: This is the first quantitative systematic review which tends
      to provide modest evidence on the association between informing diagnosis and
      quality of life in patients with cacner. PROSPERO REGISTRATION NUMBER:
      CRD42017060073.

PMID- 30212977
TI  - The effectiveness of non-invasive brain stimulation on arousal and alertness in
      patients in coma or persistent vegetative state after traumatic brain injury:
      Protocol of systematic review and network meta-analysis.
AB  - BACKGROUND: Traumatic brain injury is a leading cause of death and disability
      worldwide. The survivors usually suffer from disorders of consciousness,
      especially coma state and persistent vegetative state. For these patients, there
      is no standard treatment for them, but non-invasive brain stimulations are
      considered as relatively more acceptable treatments. However, the knowledge
      regarding the relative effectiveness and the rank of the effectiveness of the non
      invasive brain stimulations is limited. Thus, in this study, we aim to conduct a
      systematic review and network meta-analysis to evaluate the effect of non
      invasive train stimulations on arousal and alertness in patients in a coma or
      persistent vegetative state after traumatic brain injury. METHODS AND ANALYSIS: A
      comprehensive search strategy will be performed in the relevant databases
      (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, World Health
      Organization (WHO) International Clinical Trials Registry Platform (ICTRP),
      Chinese Biomedical Literature Database, China National Knowledge Infrastructure,
      Wan Fang Data). The random or quasi-random controlled trails focusing on the
      effectiveness of the non-invasive brain stimulations will be included. The risk
      of bias for the included studies will be appraised using the Cochrane
      collaboration tool for assessing risk of bias. The standard pairwise meta
      analysis and a Bayesian network meta-analysis will be conducted. ETHICS AND
      DISSEMINATION: This research is a systematic review and network meta-analysis.
      Thus, there is no requirement of ethical approval and patient informed consent.
      PROSPERO REGISTRATION NUMBER: CRD42018104945.

PMID- 30212978
TI  - Herbal medicine (Gancao Xiexin decoction) for Behcet disease: A systematic review
      protocol.
AB  - BACKGROUND: Behcet disease (BD) is a systemic vasculitis that causes blood vessel
      inflammation throughout body and no cure exists. The purpose of this review is to
      evaluate the safety and efficacy of Gancao Xiexin Decoction (GCXX) in the
      treatment of BD and provide a clinical reference for the treatment of the
      refractory disease. METHODS: First, the researcher will retrieve the following
      database based on the established search strategy: MEDLINE (PubMed), the Cochrane
      Central Register of Controlled Trials (CENTRAL), EMBASE, Allied and Complementary
      Medicine Database (AMED), China National Knowledge Infrastructure, Wanfang, VIP
      (Journal Integration Platform). The quality of the literature will be evaluated
      according to Cochrane's handbook and review inclusion criteria. Data will be
      extracted and data of sufficient homogeneity was combined using Review Manager
      (RevMan) software V5.3.5. RESULTS: This study will provide a high quality
      synthesis of herbal medicine (Gancao Xiexin decoction) for Behcet disease.
      CONCLUSIONS: The conclusion of our systematic review will provide evidence to
      judge whether herbal medicine (Gancao Xiexin decoction) for Behcet disease is an
      effective intervention for patient with menopausal women. TRIAL REGISTRATION
      NUMBER: PROSPERO CRD 42018104099.

PMID- 30212979
TI  - The protective effect of different dialysis types on residual renal function in
      patients with maintenance hemodialysis: A systematic review and meta-analysis.
AB  - BACKGROUND: Residual renal function (RRF) is an important determinant of
      mortality and morbidity in patients undergoing hemodialysis. Different dialysis
      types may have different effects on RRF. We therefore conducted this meta
      analysis to examine the RRF protective effect of different dialysis types for
      hemodialysis patients. METHODS: A systematic search was performed on PubMed,
      EMbase, Web of Science, Chinese Biomedical Literature Database, Wanfang database,
      and China National Knowledge Infrastructure for randomized controlled trials and
      cohort studies. Dialysis types included low-flux hemodialysis (LFHD), high-flux
      hemodialysis (HFHD), hemodiafiltration (HDF), and hemodialysis and hemoperfusion
      (HD+HP). The mean of endogenous creatinine clearance rate (CCR) and urea
      clearance rate (Curea), or urine volume was used to estimate RRF [95% confidence
      interval (95% CI), 6.05-16.80]. RESULTS: There were 12 articles involving 1224
      patients, including 11 random controlled trials and 1 cohort study. Meta-analysis
      showed that the RRF protective effect of HFHD [mean difference (MD) = 1.48, 95%
      CI (2.11 to 0.86), P < .01] and HD+HP [MD = 0.41, 95% CI (0.69 to 0.12), P =
      .005] was better than that of LFHD, and the RRF decline rate was the lowest in
      HFHD group [MD = 0.13, 95% CI (0.17 to 0.09), P < .01]. Descriptive analysis
      showed that HDF could better protect RRF when compared with LFHD. However, there
      was no consistency among other interventions when removing LFHD due to limited
      data. CONCLUSION: For patients undergoing maintenance hemodialysis, the HFHD,
      HD+HP and HDF may better protect RRF, compared with LFHD.

PMID- 30212980
TI  - Retroperitoneal ganglioneuroma combined with scoliosis: A case report and
      literature review.
AB  - RATIONALE: Ganglioneuroma (GN) is a rare tumour arising from the sympathetic
      nervous system. GN is constantly asymptomatic, easily ignored and likely damages
      other organs during tumour progression. PATIENT CONCERNS: The case report
      involved a 21-year-old girl who was admitted to a hospital because of a computed
      tomography result after her pregnancy examination showed retroperitoneal tumour
      and scoliosis. The scoliosis was considered as a tumour complication. DIAGNOSES:
      The tumour was finally diagnosed as GN by pathological examination.
      INTERVENTIONS: We carried out surgical treatment and performed a pathological
      examination on postoperative tumour specimens. OUTCOMES: The patient was followed
      up for 19 months and did not show tumour recurrence. However, the condition of
      the scoliosis did not improve. LESSONS: This paper reports a case of GN with
      scoliosis at the same time. GN is a benign tumour consisting of cells with a
      special origin. GN grows extensively and leads to different complications.
      Presently, pathological examination after an operation is the only approach to
      formulate an exact diagnosis. We should consider the possibility of
      retroperitoneal tumour, especially GN, if a patient suffers from scoliosis with
      an unknown cause. Thus, CT and MRI are needed to provide additional information
      that would help formulate a diagnosis.

PMID- 30212981
TI  - A multicenter, randomized, and double-blind phase IV clinical trial to compare
      the efficacy and safety of fixed-dose combinations of amlodipine
      orotate/valsartan 5/160 mg versus valsartan/hydrochlorothiazide 160/12.5 mg in
      patients with essential hypertension uncontrolled by valsartan 160 mg
      monotherapy.
AB  - BACKGROUND: To determine whether the effectiveness and safety of fixed-dose
      combinations (FDCs) of amlodipine orotate/valsartan (AML/VAL) 5/160 mg are
      noninferior to those of valsartan/hydrochlorothiazide (VAL/HCTZ) 160/12.5 mg in
      hypertensive patients with inadequate response to valsartan 160 mg monotherapy.
      METHODS: This 8-week, active-controlled, parallel-group, fixed-dose, multicenter,
      double-blind randomized controlled, and noninferiority trial was conducted at 17
      cardiovascular centers in the Republic of Korea. Eligible patients had mean
      sitting diastolic blood pressure (msDBP) >=90 mm Hg despite monotherapy with
      valsartan 160 mg for 4 weeks. Patients were randomly assigned to treatment with
      AML/VAL 5/160 mg FDC (AML/VAL) group or VAL/HCTZ 160/12.5 mg FDC (VAL/HCTZ) group
      once daily for 8 weeks. A total of 238 patients were enrolled (AML/VAL group, n =
      121; VAL/HCTZ group, n = 117), of whom 228 completed the study. RESULTS: At 8
      weeks after randomization, msDBP was significantly decreased in both groups (
      9.44 +/- 0.69 mm Hg in the AML/VAL group and -7.47 +/- 0.71 mm Hg in the VAL/HCTZ
      group, both P < .001 vs baseline). Between group difference was -1.96 +/- 1.00 mm
      Hg, indicating that AML/VAL 5/160 mg FDC was not inferior to VAL/HCTZ 160/12.5 mg
      FDC at primary efficacy endpoint. Control rate of BP defined as the percentage of
      patients achieving mean sitting SBP (msSBP) <140 mm Hg or msDBP <90 mm Hg (target
      BP) from baseline to week 8 was significantly higher in the AML/VAL group than
      that in the VAL/HCTZ group (84.3% [n = 102] in the AML/VAL group vs 71.3% [n =
      82] in the VAL/HCTZ group, P = .016). At 8 weeks after randomization, mean uric
      acid level was significantly increased in the VAL/HCTZ group compared to that at
      baseline (0.64 +/- 0.08 mg/dL; P < .001). However, it was slightly decreased from
      baseline in the AML/VAL group (-0.12 +/- 0.08 mg/dL; P = .085). The intergroup
      difference was significant (P < .001). CONCLUSION: The effectiveness and safety
      AML/VAL 5/160 mg FDC are noninferior to those of VAL/HCTZ 160/12.5 mg FDC in
      patients with hypertension inadequately controlled by valsartan 160 mg
      monotherapy.

PMID- 30212982
TI  - Olanzapine with ondansetron and dexamethasone for the prevention of cisplatin
      based chemotherapy-induced nausea and vomiting in lung cancer.
AB  - Olanzapine is an atypical antipsychotic that has shown efficacy for the treatment
      of nausea, anxiety, and insomnia. This study was conducted to evaluate the
      efficacy of olanzapine (5 mg) combined with 5-HT3 receptor antagonists and
      dexamethasone for the prevention of chemotherapy-induced nausea and vomiting
      (CINV) in lung patients receiving cisplatin-based (25 mg/m2 d1-3) highly
      emetogenic chemotherapy (HEC).Olanzapine (5 mg) was administered a day prior to
      cisplatin administration and continued on days 1 to 5. We evaluated complete
      response (CR) rate and rates of no nausea and no vomiting in 3 periods. In
      addition, Self-Rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS),
      and The Functional Living Index-Emesis (FLIE) questionnaire were also assessed.A
      total of 40 lung cancer patients were included. CR for acute, delayed, and over
      all phases were 82.5%, 75.0%, and 70.0%, respectively. The rate of no nausea in
      the acute phase was 70.0% and 62.5% in delayed phase. The rate of no vomiting in
      the acute phase was 85.0%, and 77.5% in delayed phase. The rate of no nausea and
      no vomiting in the overall phase were 57.5% and 75.0%, respectively. The median
      SAS and SDS score were 37.9 and 41.6 in pre-chemotherapy, respectively. Up to day
      6 after chemotherapy treatment, the median SAS and SDS score were 36.9 and 42.0,
      respectively. The median FLIE score was 111.7. The main side effects were grade 1
      somnolence (35.0%) and mild constipation (52.5%).Around 5 mg olanzapine may be
      used as a potential, safe, and cost-beneficial alternative to prevent nausea and
      vomiting for HEC, particular for multiday chemotherapy regimen.

PMID- 30212983
TI  - Prodromal angina and risk of 2-year cardiac mortality in patients with ST-segment
      elevation myocardial infarction undergoing primary percutaneous intervention.
AB  - We sought to investigate the prognostic significance of prodromal angina (PA) in
      unselected patients with ST-segment elevation myocardial infarction (STEMI)
      undergoing primary percutaneous coronary intervention (PPCI) and its additive
      predictive value to the GRACE score.We prospectively enrolled 3015 consecutive
      STEMI patients undergoing PPCI. Patients were divided in 2 groups according to
      the presence or absence of PA. Multivariable Cox regression was used to establish
      the relation to 2-year cardiac mortality of PA.The mean age of the study
      population was 68 (+/-14) years; 2178 patients (72%) were male. During follow-up,
      395 (13%) patients died with 278 of these (9.2%) suffering from cardiac
      mortality. Kaplan-Meier estimates showed a survival rate of 95% and 87% for
      patients with PA and no PA, respectively (log rank test < 0.001). After
      multivariable analysis, patients with PA had still a lower risk of 2 years'
      cardiac mortality compared with patients without PA (adjusted hazard ratio =
      0.50; 95% confidence interval [CI] 1.06-1.81, P = .001). Evaluation of net
      reclassification improvement showed that reclassification improved by 0.16% in
      case patients, whereas classification worsened in control patients by 1.08%
      leading to a net reclassification improvement of -0.93% (95% CI: -0.98, -0.88).In
      patients with STEMI undergoing PPCI the presence of PA is independently
      associated with a lower risk of 2-year cardiac mortality. However, the
      incorporation of this variable to the GRACE score slightly worsened the
      classification of risk. Accordingly, it seems unlikely that the evaluation of PA
      may be useful in clinical practice.

PMID- 30212984
TI  - Syncope and hypotension associated with carotid sinus hypersensitivity in a
      patient with nasopharyngeal carcinoma: A case report.
AB  - RATIONALE: Carotid sinus hypersensitivity (CSH) is traditionally classified into
      3 subgroups: cardioinhibitory, vasodepressor, and mixed subtypes. However, the
      underlying mechanism of CSH in head and neck cancer is controversial. Several
      pathological mechanisms of CSH have been proposed: atherosclerotic noncompliance,
      sternocleidomastoid proprioceptive denervation, and generalized autonomic
      dysfunction. PATIENT CONCERNS: We reported a 75-year-old man who had recurrent
      syncope attacks secondary to hypotension and reduced plasma norepinephrine (NE)
      levels. CSH was suspected when carotid massage induced syncope-like symptom.
      DIAGNOSES: Nasopharynx carcinoma with regional lymph node involvement and CSH.
      INTERVENTIONS: On admission, dopamine was administered to maintain the blood
      pressure. When NE deficiency was confirmed, intravenous NE combined with oral
      midodrine replaced the dopamine treatment. OUTCOMES: The syncopal episodes
      completely resolved with periodic occurrence of hypertension. LESSONS: Our case
      suggests a potential role of carotid sinus in regulating the release of NE in
      adrenal gland and that the monitoring of catecholamine level is recommended in
      the CSH cases either from head and neck tumors or other mechanical manipulation
      of carotid sinus.

PMID- 30212985
TI  - Case report: two cases of extremely rare primary pure squamous cell carcinoma of
      the breast.
AB  - RATIONALE: Since primary pure squamous cell carcinoma of the breast is a rare
      disease, few reports describe the characteristic findings on performing
      preoperative imaging that can be used to distinguish it from normal breast
      cancer. The rapid evolution and lack of an established method of treatment has
      resulted in several reports of advanced cases of primary pure squamous cell
      carcinoma of the breast. PATIENT CONCERNS: Case 1 was a 44-year-old woman with an
      elastic, hard tumor in the left C region. Ultrasonographic analysis revealed a
      maximal 11-mm hypoechoic area. Histologically, the tumor was a well
      differentiated squamous cell carcinoma with prominent keratinization, and there
      was prominent inflammatory cell infiltration, necrosis, and fibrosis. Case 2 was
      a 58-year-old woman with an elastic, hard tumor in the left C/D region.
      Ultrasonographic analysis revealed a maximal 31-mm hypoechoic area with partially
      calcified areas and a hyperechoic margin. Histologically, the tumor was a
      squamous cell carcinoma with prominent keratinization exhibiting an infiltrative
      growth pattern. The tumor had no connection to the epidermis and partially
      transitioned into the atypical ductal epithelium in the area surrounding the
      focus. DIAGNOSES: The patient in Case 1 was preoperatively diagnosed with T1cN0M0
      Stage I cancer of the left breast, but both patients were finally diagnosed with
      T2N0M0 Stage IIA cancer. INTERVENTIONS: Case 1: left partial mastectomy and
      axillary lymph node dissection were performed. The patient was administered 4
      courses of FEC100 and 4 courses of DTX as postoperative adjuvant therapy. Case 2:
      left modified radical mastectomy and axillary lymph node dissection were
      performed without any postoperative adjuvant therapy. OUTCOMES: Case 1: no sign
      of relapse was observed, but the patient moved away from the area to another
      hospital in March 2014 and eventually died due to relapse in January 2016. Case
      2: four years after surgery, no relapse has been observed. LESSONS: We should
      always keep the presence of primary pure squamous cell carcinoma among breast
      cancers in mind although the crisis rate is very low. Due to its high malignancy,
      needle biopsy and aspiration biopsy cytology should be performed to make a
      definitive diagnosis.

PMID- 30212986
TI  - Gastric adenocarcinoma of fundic gland mucosa type localized in the submucosa: A
      case report.
AB  - RATIONALE: Gastric adenocarcinoma of fundic gland type (GA-FG) is a new
      histological type of gastric cancer manifesting with differentiation into a
      fundic gland. Furthermore, gastric adenocarcinoma of fundic gland mucosa type (GA
      FGM) is a tumor that shows differentiation into not only a fundic gland but also
      foveolar epithelium and a mucous gland. These tumors tend to invade the
      submucosal layer. However, no cases of these tumors being localized only in the
      submucosa have been reported. Here, we present a case of GA-FGM localized in the
      submucosa and describe the cytological features of this tumor. To our knowledge,
      this is the first reported case of GA-FGM localized in the submucosa. PATIENT
      CONCERNS: A man in his early 70s was referred to our institution because of the
      detection of a gastric submucosal tumor during a health checkup. DIAGNOSES:
      Gastric adenocarcinoma of fundic gland mucosa type. INTERVENTIONS: Endoscopic
      ultrasound-guided fine-needle aspiration (FNA), endoscopic submucosal dissection
      (ESD), and total gastrectomy with lymph node dissection were performed. OUTCOMES:
      The FNA specimen showed epithelial cells with low-grade atypia. In the ESD
      specimen, adenocarcinoma showing a gastric fundic gland mucosa-like morphology
      was observed. Immunohistochemical analysis showed positive staining for
      pepsinogen I, H+/K+-adenosine triphosphatase, MUC6, and MUC5AC and negative
      staining for MUC2 and CD10, indicating tumor differentiation into fundic gland
      mucosa. Therefore, the tumor was diagnosed as GA-FGM, with localization in the
      submucosal layer. Total gastrectomy and lymph node dissection were performed
      because of the positive margins of the ESD specimen. Neither residual tumor nor
      lymph node metastasis was detected; however, many foci of heterotopic gastric
      glands (HGGs) were observed in the gastric wall, suggesting that GA-FGM arose
      from an HGG. After treatment, no recurrence was observed during a 1-year follow
      up period. LESSONS: Various tumors may arise from HGGs. Furthermore, when an FNA
      specimen shows gastric fundic gland mucosa-like epithelial cells with weak
      atypia, the possibility of GA-FG and GA-FGM should be considered.

PMID- 30212987
TI  - Successful management of a spontaneous viable monochorionic diamniotic twin
      pregnancy on cesarean scar with systemic methotrexate: A case report.
AB  - RATIONALE: Cesarean scar twin pregnancy is exceedingly rare and it remains to be
      a life-threatening condition even in the early weeks of gestation. Because of its
      rare occurrence, there is no consensus on the treatment modality of cesarean
      ectopic pregnancy. PATIENT CONCERNS: A 41-year-old, woman, gravida 7, para 6,
      with a history of low transverse cesarean section 2 years back presented with an
      estimated 6 weeks gestational age and viable spontaneous twin, monochorionic
      diamniotic gestation. The patient presented to the Emergency Department with
      complaints of vaginal bleeding and mild lower abdominal pain for 5 days.
      DIAGNOSES: An ultrasound examination was performed demonstrating a single
      intrauterine gestational sac with 2 viable embryos (monochorionic diamniotic)
      implanted in the lower uterine segment at the level of the prior cesarean section
      scar. A diagnosis of viable cesarean scar twin pregnancy was made. INTERVENTIONS:
      A 2 doses of 50 mg/m methotrexate (MTX) was given intramuscularly. The response
      to the treatment was monitored by serial beta-human chorionic gonadotropin (beta
      hCG) and ultrasound. OUTCOMES: Patient was followed up with beta-hCG weekly
      levels which became 0 after 68 days of treatment. During the follow-up, the
      patient was asymptomatic, no side effects of MTX were noticed. LESSONS: We
      reported a rare case of viable monochorionic diamniotic twin pregnancy on a
      cesarean scar that was successfully treated with systemic MTX without any
      additional therapy. Additionally, the decline of beta-hCG in twin ectopic
      cesarean scar pregnancy appears to be similar to a singleton ectopic pregnancy.

PMID- 30212988
TI  - Evaluation of T cell infiltration in matched biopsy and nephrectomy samples in
      renal cell carcinoma.
AB  - T cell infiltration in tumors has been investigated as a biomarker of response to
      checkpoint inhibitors. Neo-adjuvant studies in renal cell carcinoma (RCC) may
      provide a unique opportunity to compare T cell infiltration in a pretreatment
      renal mass biopsy to a posttreatment nephrectomy specimen, and thus evaluate the
      effects of immune checkpoint inhibitors. However, there are no data regarding the
      association of T cell infiltration in matched biopsy and nephrectomy samples
      without intervening treatment. Understanding this association will inform
      investigation of this potential biomarker in future studies.Matched biopsy and
      nephrectomy samples (without intervening systemic therapy) were identified from
      patients with nonmetastatic RCC. Selected tissue sections from biopsy and
      nephrectomy samples were reviewed and marked for intratumoral lymphocytes by a
      pathologist. Immunohistochemistry (IHC) was utilized to stain for T cell markers
      (CD3, CD4, and CD8). Intratumoral staining was then quantified in the tissue
      sections as counts per total tumor area surveyed. Spearman correlation (r) was
      used to measure associations.Thirty matched pairs were investigated. The median
      interval between biopsy and nephrectomy was 2.8 (0.2-87.7) months. Clear cell was
      the most common histology (29/30; 97%). There was a statistically significant
      positive correlation between the frequency of CD3 and CD8 T cells between matched
      biopsy and nephrectomy samples (r = 0.39; P = .036 and r = 0.38; P = .041,
      respectively).The frequencies of CD8+ T cells in matched biopsy and nephrectomy
      samples in RCC in the absence of intervening treatment have been characterized
      and show a positive correlation between matched biopsy and nephrectomy samples.

PMID- 30212989
TI  - Transition patients: Adults with chronic pediatric disorder presenting to a
      tertiary pediatric emergency department in Korea.
AB  - The primary objective was to evaluate the characteristics of adults (>=18 years
      old) with chronic pediatric disorders (transition patients) who visited the
      pediatric emergency department (PED). The secondary objective was to determine
      the associated factors for their admission.This study was a retrospective chart
      review of transition patients seen at a large, urban PED in Korea from 2010 to
      2015. Epidemiologic and clinical data were used to identify the characteristics
      of transition patients compared with those of pediatric patients in the PED. A
      multivariable logistic regression model was used to calculate odds ratios (ORs)
      for the factors associated with hospitalization.Transition patients accounted for
      2776 (2.4%) of the total encounters. A total of 463 (38.9%) of the transition
      patients had >1 visit. Congenital heart disease was the most common (23.2%)
      chronic pediatric disorder. Most encounters (94.5%) were related to an underlying
      disorder, and 34.4% of the encounters required consultations with other pediatric
      subspecialties. Diagnostic procedures were performed in 90.1% of the encounters.
      Transition patients were hospitalized more than pediatric patients (35.3% vs
      15.3%; P < .001). The associated factors for admission in the transition patients
      were chronic gastrointestinal disorder (adjusted odds ratio [AOR]: 3.76 [95%
      confidence interval, CI, 2.29-6.16]), complaints related to an underlying
      disorder (AOR: 3.13 [95% CI, 1.94-5.05]), respiratory complaints (AOR: 2.02 [95%
      CI, 1.33-3.08]), and infectious complaints (AOR: 1.97 [95% CI, 1.40-2.76]).A
      substantial number of transition patients used the PED, and they required a
      larger amount of resources in the PED. Chronic gastrointestinal disorder,
      respiratory symptoms, or complaints related to an underlying disorder were the
      related factors for admission of transition patients.

PMID- 30212990
TI  - Maternal anaphylactic shock in pregnancy: A case report.
AB  - RATIONALE: Anaphylaxis is a very rare event in pregnancy, triggering maternal
      hypotension leading to intrapartum hypoxic-ischemic encephalopathy in infant.
      Furthermore, cesarean sections are performed at a high rate in anaphylactic
      pregnant women. PATIENT CONCERNS: A 34-year-old pregnant woman presented with
      maternal anaphylaxis following prophylactic antibiotic injection for cesarean
      section. Within a few minutes after initiation of intradermal skin test with
      cefotetan, the pregnant woman developed generalized itchy rash, chest tightness,
      and dyspnea. DIAGNOSES: Several minutes after the injection of antibiotics, a
      diffuse urticarial rash was detected over her face and trunk followed by
      complaints of chest tightness and dyspnea. She was diagnosed with hypotension and
      hypoxia. Further, fetal heart tones showed bradycardia. A presumptive diagnosis
      of anaphylactic reaction induced by cefotetan was made for surgical prophylaxis.
      INTERVENTIONS: The patient was managed for anaphylaxis, via administration of
      epinephrine, glucocorticoid, and antihistamine. Emergency cesarean section
      performed under general anesthesia resulted in a favorable perinatal outcome for
      the fetus. OUTCOMES: Maternal and fetal outcomes were good after prompt treatment
      for anaphylaxis and emergency cesarean section. LESSONS: This is the first
      reported case of anaphylaxis following cefotetan administration in pregnancy.
      Cefotetan, a second-generation cephalosporin, is a commonly prescribed antibiotic
      used to treat a wide range of bacterial infections. The case demonstrated life
      threatening anaphylactic reaction during pregnancy. Even a skin test using
      antibiotics alone triggered anaphylaxis.

PMID- 30212991
TI  - The role of pelvic lymphocele in the development of early postoperative
      complications.
AB  - With the increasing incidence of gynecologic malignancy, radical hysterectomy
      represents an important part of the adequate treatment of these patients. The
      pelvic lymphocele is a known side effect of pelvic and para-aortic
      lymphadenectomy. The aim of our study was to assess the role of the lymphocele in
      the development of early postoperative complications.A single-center,
      retrospective analysis between January 2000 and May 2017 revealed 1867 patients
      with cervical and endometrial cancer, treated through radical or modified radical
      hysterectomy and pelvic lymphadenectomy. Postoperative complications and the
      occurrence of pelvic lymphocele were evaluated.Approximately 47.6% of patients
      were diagnosed with pelvic lymphocele, with only 5.2% being symptomatic. Early
      postoperative complications rate recorded an incidence of 8.1%, occurring more
      frequent if lymphocele were present (P < .001). The pelvic lymphocele
      represented, in univariate analysis, a risk factor for the development of pelvic
      abscesses, but not for deep vein thrombosis, lymphedema, or bowel obstruction.
      Hydronephrosis was found to be significantly correlated with the pelvic
      lymphocele, but we believe this urological complication to have a different
      underlining mechanism. Neoadjuvant radiotherapy represented in both uni- and
      multivariate analysis a risk factor for the occurrence of postoperative
      complications.In the postoperative context of oncogynecological surgery, pelvic
      lymphocele occur at high rates, representing a statistical risk factor for
      hydronephrosis and pelvic abscesses, with neoadjuvant radiotherapy being an
      independent risk factor for early postoperative complications.

PMID- 30212992
TI  - Risk factors associated with nonalcohol fatty liver disease and fibrosis among
      patients with type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is closely related to hepatic steatosis and
      fibrosis. The aim of this study was to analyze the occurrence of hepatic
      steatosis and fibrosis in patients with T2DM and to explore the risk factors.A
      total of 629 patients with T2DM were enrolled. Liver stiffness value (LSV) and
      controlled attenuation parameters (CAP) were measured using Fibroscan. Liver
      fibrosis was diagnosed when LSV was greater than 7.4 kPa, and advanced liver
      fibrosis was diagnosed when LSV was greater than 10.6 kPa. Hepatic steatosis
      diagnosis was made when CAP value was greater than 238 dB/m. Demographic
      information, physical examination data, and laboratory tests results were
      collected. The 629 patients were classified into 2 groups by the liver fibrosis
      and liver steatosis, and then the difference was analyzed.Among patients
      enrolled, 231 patients were diagnosed as liver fibrosis. The age of the patients
      in the fibrosis group was significantly greater than that in the non-fibrosis
      group, and similar trends were observed in the waist-hip ratio (WHR), systolic
      blood pressure, and diastolic blood pressure. The proportion of smoking and
      alcoholic consumption was significantly lower in patients with non-fibrosis
      group. A total of 426 patients were diagnosed with liver steatosis. Body mass
      index (BMI), WHR, systolic blood pressure, and diastolic blood pressure in
      patients with steatosis were significantly higher than those in non-steatosis
      group. We observed that the LSV (P = .042) and CAP value (P < .001) are
      positively correlated with metabolic syndrome components in T2DM patients. Older
      age (OR = 1.099, P = .001), high BMI (OR = 1.088, P = .003), low platelet level
      (OR = 0.996, P = .014), and smoking (OR = 1.653, P = .013) were independent risk
      factors of liver fibrosis among T2DM patients. High BMI (OR = 1.369, P < .001),
      high diastolic blood pressure (OR = 1.048, P < .001), and high gamma glutamyl
      transpeptidase (OR = 1.018, P = .009) were independent risk factors for liver
      steatosis among T2DM patients.This study suggested risk factors screening of
      liver fibrosis and steatosis. Timely intervention should be taken into
      consideration among high risk patients to prevent progress liver diseases.

PMID- 30212993
TI  - Alpha-fetoprotein producing hepatoid gastric adenocarcinoma with neuroendocrine
      differentiation: A case report.
AB  - RATIONALE: Hepatoid gastric adenocarcinoma is a rare type of gastric cancer. The
      phenomenon of neuroendocrine differentiation (NED) in gastrointestinal tumor
      needs further research. Both hepatoid adenocarcinoma and neuroendocrine
      differentiation are the factors leading to a poor prognosis of gastric cancer.
      However, there is still no specific treatment. PATIENT CONCERNS: A 60-year-old
      man who had a pain and distention in his upper abdomen presented melena.
      Gastroscopy and pathology revealed a gastric cancer. DIAGNOSES: Postoperative
      pathology revealed a hepatoid gastric adenocarcinoma. Immunohistochemical
      analysis showed a-fetoprotein (AFP), hepatocyte, synaptophysin (Syn), and
      chromogranin A (CgA) positive, and Ki67 60% positive. A-fetoprotein producing
      hepatoid gastric adenocarcinoma with NED is diagnosed. INTERVENTIONS: The patient
      was treated with an R2 radical gastrectomy, but refused chemotherapy. OUTCOMES:
      The AFP level was >2000 ng/mL (0-8.78) half a year after the surgery. There was
      no obvious abnormality from computed tomography (CT). The patient refused
      positron emission tomography computed tomography (PET-CT) and left the hospital.
      LESSONS: Hepatoid adenocarcinoma and neuroendocrine differentiation are the
      factors leading to a poor prognosis of gastric cancer. It relapses easily. Long
      term follow-up and regular examinations are necessary to detect relapses.

PMID- 30212994
TI  - Neurosurgical anesthesia for a pregnant woman with macroprolactinoma: A case
      report.
AB  - RATIONALE: Being required to perform neurosurgery on a pregnant woman is rare,
      but occasionally unavoidable. In these cases, clinical anesthesiologists are
      confronted with conflicting information and few evidence-based guidelines.
      PATIENT CONCERNS: Here, we describe the successful anesthetic management of a 24
      week pregnant woman with macroprolactinoma who underwent endonasal
      transsphenoidal resection of pituitary adenoma. DIAGNOSES: According to the
      prolactin (PRL) level and magnetic resonance imaging (MRI) results, the patient
      was diagnosed with macroprolactinoma and kept stable after taking the regular
      bromocriptine treatment. However, after stopping the drug by herself because of
      pregnancy, her tumor increased in size and she suffered from vision loss. Surgery
      was recommended as soon as possible to lessen the compression in the eye.
      However, the anesthetic management was a considerable risk due to the increased
      chance of maternal mortality, intrauterine growth restriction, or preterm labor.
      INTERVENTIONS: We held a multidisciplinary meeting before the operation and made
      a detailed plan for how to proceed. During the operation, our team ensured
      intensive monitoring, provided adequate oxygen, and achieved haemodynamic
      stability. Anesthetics like sufentanyl, rocuronium, propofol, and desflurane were
      carefully chosen in order to ensure the safety of both the mother and fetus.
      OUTCOMES: Under the careful and successful anesthetic management, the pregnant
      woman underwent the surgery smoothly and neither the mother nor baby experienced
      any pre- or postoperative complications. At the 38th week of gestation, the
      patient received a cesarean section and the baby had developed normally. LESSONS:
      Neurosurgeries in pregnancy are sparse, and careful planning with cross
      disciplinary specialists was needed in advance of the operation. Moreover, when
      dealing with such surgeries, we should consider the safety of both the mother and
      fetus, which is challenging but important.

PMID- 30212995
TI  - Clinical course and treatment outcomes of toxocariasis-related eosinophilic
      disorder.
AB  - Blood eosinophilia is a common clinical finding. Helminthic infections, including
      toxocariasis, are a common cause of eosinophilia; however, the clinical course of
      toxocariasis associated with eosinophilia is not fully understood. Thus,
      controversies exist regarding treatment indications.To evaluate the clinical
      features and natural course of various types of eosinophilia, with a particular
      focus on toxocariasis, we retrospectively reviewed the medical records of 1000
      patients with peripheral blood eosinophilia who were referred to the allergy
      clinic at Asan Medical Center between 2007 and 2012. Clinical parameters and
      imaging study findings were evaluated. The treatment response to albendazole and
      resulting changes in eosinophilia and imaging studies were analyzed in patients
      diagnosed with toxocariasis.Among the 1000 subjects, toxocariasis was the most
      common cause of eosinophilia (n = 534; 53.4%), followed by allergic disease and
      adverse drug reactions. The majority of patients with toxocariasis were men, and
      they were mostly asymptomatic. More than one-third of patients (n = 215; 40.3%)
      with toxocariasis exhibited organ involvement, particularly hepatic involvement.
      In most cases of eosinophilia and organ involvement due to toxocariasis, the
      symptoms normalized regardless of treatment.Most cases of eosinophilia related to
      toxocariasis displayed a self-remitting course regardless of treatment. With the
      exception of several clinical situations, including ocular involvement, the
      clinical need for anti-helminthic therapy in toxocariasis is not that
      significant.

PMID- 30212996
TI  - A case report of CRB2 mutation identified in a Chinese boy with focal segmental
      glomerulosclerosis.
AB  - RATIONALE: Focal segmental glomerulosclerosis (FSGS) is a common disease
      resulting in end-stage renal disease. The incidence of FSGS is increasing in
      Western countries. The clinical manifestations include proteinuria,
      hypoproteinemia, oedema, and hypertension. Single-gene heritable mutations are
      considered to be the source of FSGS pathogenicity according to recent in-depth
      studies on the pathogenesis. Here, we first reported the case of a Chinese boy
      whose histology presented with FSGS caused by a compound heterozygous mutation.
      PATIENT CONCERNS: A 7-year-old Chinese boy was repeatedly admitted to our
      hospital for fever, cough, and proteinuria since he was 1.6 years old. DIAGNOSES:
      FSGS was identified by renal biopsy. Whole exome sequencing (WES) showed that a
      novel mutation of crumbs homolog 2 (CRB2) was identified in a Chinese boy with
      FSGS. INTERVENTIONS: Patient was treated with low-dose corticosteroid and
      mycophenolate mofetil for maintenance therapy. OUTCOMES: At last follow-up,
      protein (+~++) was observed in his urinalysis. LESSONS: We identified a novel
      mutation of CRB2 in a Chinese boy with FSGS that had never been described in a
      previous report. These findings suggested that mutations in recessive disease
      genes are more frequent among early-onset disease.

PMID- 30212997
TI  - Total en bloc spondylectomy for primary tumors of the lumbar spine.
AB  - This was a retrospective clinical study.This study aimed to evaluate our
      institution's experience with total en bloc spondylectomy (TES) in patients
      treated for primary lumbar spine tumors and investigate postoperative clinical
      outcomes.TES is a widely accepted by spinal and musculoskeletal surgical
      oncologists and results in favorable health-related quality of life outcomes.
      However, this procedure still imposes major risks and complications.The cases of
      TES performed for primary lumbar spine tumors between 1993 and 2015 were
      retrospectively analyzed. Primary outcome measures were the rates of
      perioperative complications and reoperation for instrumentation failure.We
      enrolled 30 patients (13 men and 17 women; median age and follow-up, 38 years and
      87 months, respectively). Three, 7, and 5 cases involved previous radiotherapy,
      intralesional resection, and chemotherapy, respectively. The most common tumor
      was giant cell tumor (14 cases) followed by osteosarcoma (4 cases) and
      plasmacytoma (3 cases). The median estimated blood loss was 1450 mL, and the
      median operative time was 11 hours. At least 1 perioperative complication
      occurred in 26 patients (86.7%), with the most common being postoperative muscle
      weakness (24 patients, 80.0%) followed by surgical site infection and
      postoperative cerebrospinal fluid leakage (7 patients, respectively; 23.3% each).
      Revision surgery for instrumentation failure was required in 6 patients (20.0%)
      at a median of 33 months after the index TES. Four patients experienced local
      tumor recurrence (13.3%), and their 10-year disease-free rate was 75.0%.TES is a
      feasible and effective procedure for primary lumbar spine tumors, but the risks
      of perioperative complications and late instrumentation failure should be
      acknowledged. Surgical oncologic outcomes were good, especially in patients who
      underwent TES as their first surgical treatment. Therefore, being familiar with
      the indications for TES and the surgical technique is important.

PMID- 30212998
TI  - The optimal anticoagulant therapy for mechanical heart valves in a gallbladder
      cancer patient with hepatic metastases: A case report.
AB  - RATIONALE: Developing an optimal anticoagulant strategy poses a challenging task
      in patients with mechanical heart valves (MHVs) throughout their lifetime. We
      report an optimal anticoagulant therapy in a cancer patient with hepatic
      metastases after MHV replacement. PATIENT CONCERNS: A 68-year-old female with
      MHVs suffered from gallbladder cancer with hepatic metastases. Her international
      normalized ratio (INR) fluctuated owing to the declined hepatic function.
      DIAGNOSES: Gallbladder cancer and hepatic metastases, with a history of mechanic
      aortic valve replacement and mitral valve replacement. INTERVENTIONS: Warfarin
      was discontinued and Vitamin K1 was immediately administrated via intravenous
      infusion. low-molecular-weight heparin (LMWH) was regarded as a preferable
      option, and nadroparin at the dosage of 4100IU daily was administered. OUTCOMES:
      No adverse event occurred during the patient's hospitalization and two-week
      follow up after discharge. LESSONS: LMWH may represent a reasonable alternative
      regarding the inhibition of thrombus and bleeding in MHVs carriers with cancer
      and hepatic metastases.

PMID- 30212999
TI  - Novel biochemical predictors of unfavorable prognosis for stable coronary
      disease.
AB  - Successful risk stratification is necessary for optimum management of patients
      after acute coronary syndrome (ACS). The aim of the study was to evaluate the
      role of novel biochemical markers in the prediction of adverse cardiovascular
      events in stable patients several years after ACS.The study group was randomly
      selected from all ACS patients treated with reperfusion therapy between 2002 and
      2003 at 1st Department of Cardiology, Medical University of Warsaw, Poland. All
      patients were readmitted to hospital between 2010 and 2011 for clinical and
      biochemical cardiovascular risk factors assessment and were prospectively
      observed for 30-months follow-up. The primary endpoint was all-cause death or
      hospital readmissions due to a cardiovascular condition at 30 months. The
      secondary endpoint was a composite of all-cause death or hospitalization-related
      noncardiovascular condition during the follow-up.The study population consisted
      of 146 patients (mean age 66.6 +/- 9.8 years; 60 female). The primary and
      secondary endpoints occurred in 49 and 65 patients, respectively. Univariate
      analysis demonstrated that out of 17 analyzed biomarkers only high-sensitive C
      reactive protein (hsCRP), Soluble Fms-Like Tyrosine kinase-1 (sFlt-1), and
      endothelin-1 (ET-1) were significantly associated with primary end-point and N
      Terminal pro-B-type natriuretic peptide (NT-proBNP), hsCRP, ET-1, sFlt-1, and
      procalcitonin (PCT)-with secondary end-point. Multivariate analysis demonstrated
      that concentration of sFlt-1 was the only independent factor associated with
      primary end-point (P = .007 and P = .025, respectively), whereas NT-proBNP and
      hsCRP levels were only associated with secondary end-point (P = .004 and P =
      .001, respectively).sFlt-1, NT-proBNP, and hsCRP are associated with adverse
      outcomes in stable patients several years after ACS and may emerge as useful
      clinical biomarkers to enhance stratify patient's risk.

PMID- 30213000
TI  - Impact of neutrophil-lymphocyte ratio on long-term outcome in patients with
      craniopharyngioma.
AB  - Neutrophil-lymphocyte ratio (NLR) is a poor prognostic factor in many tumors
      including glioblastoma multiforme (GBM), colorectal, and prostate cancer. The aim
      of this study was to investigate the prognostic value of preoperative NLR in
      patients with craniopharyngioma.Around 149 patients of craniopharyngioma
      surgically were treated at the Department of Neurosurgery, West China Hospital
      from January 2008 to December 2010, including 84 males and 65 females aged from 6
      to 70 years were retrospectively reviewed, and preoperative NLR was analyzed.
      Overall survival (OS), progression free survival (PFS), and quality of life (QOL)
      were evaluated.The 5-year OS and PFS rates were 81.21% and 75.84%. Preoperative
      NLR was significantly correlated with OS (HR = 1.44, 95% CI 1.16-1.79, P = .001)
      and PFS (HR = 1.46, 95% CI 1.22-1.74, P < .001). The best cut-off value of NLR
      was found to be 4 based on the receiver operator characteristics (ROC) curve.
      Patients with NLR >=4 had a significantly worse QOL (P = .039), lower OS rate (P
      = .009), and PFS rate (P < .001).Preoperative NLR may be a simple, readily
      available, and valid predictor of long-term outcome in craniopharyngioma. We
      suggest that the NLR can provide effective guidance to neurosurgeons for more
      information about the tumor and prognostic evaluation.

PMID- 30213001
TI  - Cervical disc herniation causing Brown-Sequard syndrome: Case report and review
      of literature (CARE-compliant).
AB  - RATIONALE: Brown-Sequard syndrome (BSS) is manifested as ipsilateral motor
      deficit and contralateral sensory loss. BSS caused by herniated cervical disc is
      extremely rare and easily be misdiagnosed, and clinical features of this problem
      were not fully understood. PATIENT CONCERNS: A 57-year-old man presented with a 3
      month history of weakness in his right arm, and he experienced progressive right
      hemiparesis at 2 days before admission, along with contralateral deficit in
      sensation of pain and temperature below T2. DIAGNOSES: Magnetic Resonance Imaging
      (MRI) showed severe cord compression due to a large paracentral extradural C4-C5
      cervical disc herniation (CDH). INTERVENTIONS: Subtotal cervical corpectomy,
      decompression, and fusion through anterior approach were performed. The patient
      recovered rapidly after surgery. OUTCOMES: Complete recovery of sensory and motor
      functions was obtained at a 4-months follow-up after surgery. LESSONS: Our case,
      along with a review of the literature, highlights that careful medical history
      inquiries, detailed neurologic examinations, and cervical spinal MRI scans are
      essential for diagnosis of CDH caused BSS. Prompt surgical decompression
      according to individual condition is commonly warranted. Early diagnosis with
      prompt surgical decompression could lead to favorable recovery.

PMID- 30213002
TI  - Computed tomography color mapping for evaluation of bone ongrowth on the surface
      of a titanium-coated polyetheretherketone cage in vivo: A pilot study.
AB  - Bone ongrowth on the surfaces of titanium (Ti)-coated polyetheretherketone (PEEK)
      materials has been demonstrated in animal models; however, whether this occurs on
      the surfaces of Ti-coated PEEK cages in lumbar interbody fusion has not been
      demonstrated clinically in vivo. This prospective observational study was aimed
      to develop and validate a computed tomography (CT) color mapping based on
      Hounsfield unit (HU) values for evaluation of bone ongrowth on the surfaces of
      the Ti-coated PEEK cage after posterior lumbar interbody fusion (PLIF).Twenty
      four consecutive patients (11 men and 13 women; mean age, 67.0 years; range, 20
      82 years) who underwent single- or 2-level PLIF since March 2015 were included.
      Two Ti-coated PEEK cages were inserted in all PLIF segments. From reconstructed
      sagittal planes from postoperative CT scans (within 1 week and 6 months
      postoperatively), bone ongrowth on the surfaces of cage frames was evaluated by
      CT color mapping. Inter- and intraobserver reliability of the assessment of bone
      ongrowth by CT color mapping was evaluated by Cohen's kappa coefficient. The
      relation between CT color mapping and HU values on the surfaces of cage frames
      was also analyzed.A total of 248 surfaces of cage frames were evaluated. Bone
      ongrowth was observed in 134 of 248 surfaces (54.0%) by CT color mapping.
      Intraobserver reliability for the evaluation of bone ongrowth was kappa = 0.831,
      and interobserver reliability was kappa = 0.713. The HU values in the local
      regions of interest (ROIs) on the surfaces of cage frames where the postoperative
      bone ongrowth existed on CT color mapping increased significantly postoperatively
      (P < .001), and the median postoperative change rate of the HU values in the
      local ROIs was 22.4%.The assessment of bone ongrowth on the surfaces of Ti-coated
      PEEK cages by CT color mapping had adequate inter- and intraobserver reliability,
      which was useful especially in detecting local increase in HU values on the
      surfaces of the cages. This method is an easy and visually comprehensible method
      for the assessment of bone ongrowth in the bone-implant interface.

PMID- 30213004
TI  - Cognitive behavioral therapy for insomnia combined with eszopiclone for the
      treatment of sleep disorder patients transferred out of the intensive care unit:
      A single-centred retrospective observational study.
AB  - Patients transferred out of the intensive care unit (ICU) are always impaired by
      sleep disorders. Cognitive behavioral therapy for insomnia (CBT-I) and
      eszopiclone are 2 commonly prescribed strategies for insomnia. In the current
      study, the effect of the combined application of the 2 methods on sleep disorders
      in ICU transferred out patients was assessed.Twenty-nine insomnia patients
      receiving combined treatment of CBT-I and eszopiclone and a corresponding number
      of patients treated with eszopiclone were collected. The incidence of discomfort
      experiences in ICU was recorded. Polysomnogram (PSG), Pittsburgh Sleep Quality
      Index (PSQI), self-rating anxiety scale (SAS), self-rating depression scale
      (SDS), and treatment emergent symptom scale (TESS) were used to assess the
      treatment efficacy and side effects.Hospitalization for over 7 days, use of
      benzodiazepines, and experiencing anxiety, insomnia, and mechanical ventilation
      increased chances of sleep disorders. The sleep latency, awakening time, and
      total sleep time were further improved in patients treated with the combined
      therapy than patients treated with eszopiclone (t = -2.334, -2.412, 2.383, P <
      .05). Similar changing pattern was observed for PSQI score (t = -2.262, P < .05).
      The improvement effect of the combined therapy on the sleep efficacy, SWS phase
      III, and rapid eye movement sleep was also significantly stronger (t = 2.112,
      2.268, 2.311, P < .05). Moreover, the SAS and SDS scores in patients treated with
      the combined therapy decreased more than those of patients treated with
      eszopiclone.The efficacy of CBT-I combined with eszopiclone in the treatment of
      sleep disorders in ICU transferred out patients was better than eszopiclone.

PMID- 30213003
TI  - Improved survival of hospitalized patients with cardiac arrest due to coronary
      heart disease after implementation of post-cardiac arrest care: A population
      based study.
AB  - Post-cardiac arrest care was implemented in 2010 and has been shown to improve
      the survival of patients with coronary heart disease (CHD). However, the findings
      varied for different survival conditions.We conducted a retrospective
      longitudinal study of records from 2007 to 2013 in the National Health Insurance
      Research Database. We evaluated the differences in short-term (2-day and 7-day)
      and long-term (30-day and survival to discharge) survival after the
      implementation of post-cardiac arrest care and among age subgroups. We reviewed
      inpatient datasets in accordance with the International Classification of Disease
      Clinical Modification, 9th revision codes (ICD-9-CM). Eligible participants were
      identified as those with simultaneous diagnoses of cardiac arrest (ICD-9-CM
      codes: 427.41 or 427.5) and CHD (ICD-9-CM codes: 410-414). Multiple logistic
      regression was applied to establish the relationship between calendar year and
      survival outcomes.The odds of 2-day survival from 2011 to 2013 were higher than
      those from 2007 to 2010 (adjusted odds ratio [aOR]: 1.15; 95% confidence interval
      [CI]: 1.03-1.29). Similarly, the odds of 7-day survival from 2011 to 2013 were
      higher than those from 2007 to 2010 (aOR: 1.11; 95% CI: 1.01-1.22). Improvements
      in the odds of 2-day and 7-day survival were discovered only in patients <65
      years old. Our data reinforce that short-term survival improved after
      implementation of post-cardiac arrest care. However, older age seemed to nullify
      the influence of post-cardiac arrest care on survival.

PMID- 30213005
TI  - Rationale and design of randomized controlled trial protocol of cardiovascular
      rehabilitation based on the use of telemedicine technology in the Czech Republic
      (CR-GPS).
AB  - BACKGROUND: Cardiovascular diseases remain the most common causes of death in the
      world. Instructions for secondary prevention recommend multifaceted approach in
      cardiovascular diseases risk management. Center-based physical exercise training
      is considered as an important integral part of cardiac rehabilitation (CR).
      Despite all recognized benefits CR brings, active interest of patients remains
      low in many countries, including the Czech Republic. That is why there is a need
      to focus on more effective patients' participation in CR with respect to their
      preferences and needs. One of possible approaches is using telemonitoring
      guidance based on obtaining data via technological equipment during home exercise
      training. The aim of this study is to compare effectiveness of both center- and
      home-based exercise training with focus on participants' physical fitness and
      quality of life. METHODS/DESIGN: This randomized control trial intends to monitor
      cardiorespiratory health indicators and quality of life of patients diagnosed
      with a coronary artery disease (CAD) at the University Hospital Brno, Czech
      Republic. These patients will be randomly separated into 2 groups-a regular
      outpatient group (ROT) and an intervention training group (ITG). Both groups
      undergo a 12-week rehabilitation training program. The ROT group will undergo
      center-based exercise trainings in the hospital and receive feedback and support
      directly by their coach. The ITG group will be telemonitored during exercise
      training in their home environment via a wrist sport tester and Internet
      application.All patients will be supposed to exercise at 70% to 80% of their
      heart rate reserve obtained from cardiopulmonary exercise test (CPX). The primary
      outcome is to measure and compare physical fitness values assessed at baseline
      and after 12 weeks of training. Physical fitness is expressed as peak oxygen
      uptake assessed by the CPX test. The secondary outcomes are patients, training
      adherence, and their quality of life. DISCUSSION: This trial focuses on an up-to
      date topic. As there have not been any similar trials in the Czech Republic yet,
      we expect it to bring great benefits not only for our hospital in Brno. In the
      long term, this method seems to be low-cost for all participants and brings a lot
      of benefits for those patients, who are for many reasons unable to participate in
      center-based CR provided by hospitals and other health care centers. Physical
      exercise therapy brings good results in reducing cardiovascular risk factors and
      improves its global impact. Thanks to its simplicity, it is expected to increase
      patients' training adherence as well.

PMID- 30213006
TI  - Management of lumbar radiculopathy due to disc herniation with interlaminar
      epidural steroid injection in the presence of multilevel Tarlov cysts in the
      neural foramina: A case report.
AB  - RATIONALE: Perineural cysts, commonly referred to as Tarlov cysts, are
      cerebrospinal fluid-filled dilations between the perineurium and endoneurium
      typically arising at the junction of posterior and dorsal root ganglia in the
      neural foramina. This anatomical location is in close proximity to usual needle
      trajectory during performing transforaminal epidural injection, and therefore
      presents a potential risk of dural puncture and associated complications. PATIENT
      CONCERNS: Severe lower extremity pain interfering with activities of daily
      living. DIAGNOSES: Lumbar radiculopathy secondary to left-sided L4-5 disc
      herniation in the presence of multilevel Tarlov cysts in the neural foramina.
      INTERVENTIONS: Posterior interlaminar epidural steroid injection technique was
      preferred, as opposed to transforaminal approach, to avoid potential risk of
      dural puncture and associated complications in the presence of multilevel Tarlov
      cysts in the neural foramina. OUTCOMES: The patient responded favorably to
      epidural steroid injection via interlaminar approach with complete resolution of
      pain, symptoms, and signs. There were no complications. The patient was able to
      tolerate physical therapy, wean pain medications, and achieve normal activities
      of daily living without any significant limitations. LESSONS: In patients
      presenting with an MRI report of "Tarlov cysts", meticulous evaluation of
      diagnostic images should be an essential first step before considering invasive
      spinal procedures. Should there be any presence of Tarlov cyst in close proximity
      to planned needle trajectory, we recommend appropriate modification of spinal
      intervention to avoid potential complications.

PMID- 30213007
TI  - Recent global trends in testicular cancer incidence and mortality.
AB  - Testicular cancer (TCa) has a relatively rare incidence and mortality, but has
      not been thoroughly evaluated. We analyzed global variations and recent trends in
      TCa incidence and mortality.Age-standardized rates (ASRs) of TCa incidence and
      mortality were retrieved from the GLOBOCAN 2012 database. Temporal patterns were
      assessed using data obtained from the Cancer Incidence in Five Continents
      (volumes I-X) and World Health Organization Mortality databases. The incidence
      and mortality trends over the last 10 years were analyzed using join point
      analysis.Western and Northern Europe had the highest incidence of TCa (ASR = 8.7
      and 7.2, respectively), with most countries showing an increase in incidence
      rates except for China, which had a stable incidence. Incidence rates were
      markedly increased in Southern European countries (average annual percent change
      of 6.8% in Croatia and 6.1% in Spain) but were attenuated in western Europe. The
      highest mortality rates were observed in western Asia (ASR = 0.7), with most
      countries showing a decrease in mortality.While the incidence of TCa has
      increased, mortality from TCa has decreased in most countries. More
      socioeconomically developed countries had a higher incidence of TCa with lower
      mortality.

PMID- 30213008
TI  - Comparison of perioperative flurbiprofen axetil or celecoxib administration for
      pain management after total-knee arthroplasty: A retrospective study.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal
      postoperative pain management. The purpose of this study was to evaluate the
      postoperative pain relief, time to ambulation, and opioid-sparing effects of
      flurbiprofen axetil (FA) and celecoxib (CX) after total-knee arthroplasty (TKA)
      surgery.A convenience sample of 300 patients was obtained using a retrospective
      chart review of patients who underwent TKA and received FA or CX or saline (SA)
      as control. Institutional review board approval was obtained, and 300 charts of
      patients who received TKA were reviewed. Visual analog scale (VAS) pain scores up
      to 6 months postoperatively, opioid requirements, range of knee motion, adverse
      effects, and length of hospital stay are recorded. Data were analyzed using the
      Pearson Chi-square where appropriate or the Fisher exact test, and all continuous
      variables were examined using a Wilcoxon rank test.The results of the study
      showed no significant differences between the 3 groups for the age, gender,
      American Society of Anesthesiologists class, number of patients who underwent
      knee surgery, weight, height, and operation duration. Patients in FA and CX
      demonstrated significantly reduced pain scores and less morphine consumption at
      rest and active motion compared to SA in 24 hours after surgery, with lower
      scores and less opioid requirements in the FA group. However, after 48 hours
      postoperatively, there are no significant differences between these
      groups.Intravenous application of 1 mg/kg flurbiprofen axetil twice a day and 200
      mg celecoxib once a day improved analgesia and decreased morphine consumption
      following TKA. When the 2 active drugs were compared, it was found that
      flurbiprofen axetil was superior to celecoxib in terms of short-term analgesic
      efficacy and opioid consumption.

PMID- 30213010
TI  - Primary biliary cholangitis associated with drug-induced liver injury and
      alcoholic liver fibrosis: A case report.
AB  - RATIONALE: Primary biliary cholangitis (PBC) is a liver autoimmune disease. If
      this disease is associated with other liver injury factors, both misdiagnosis and
      missed diagnosis will easily occur. Therefore, detailed disease history
      collection and related laboratory examination should be performed on patients
      with liver injury for unidentified causes. When necessary, liver biopsy should be
      performed to confirm the histopathological diagnosis. PATIENT CONCERNS: The
      subject patient was a 63-year-old Chinese male with chronic liver injury who had
      a drinking history of about 30 years and drank 500 g daily on average and began
      to take health products and dietary supplements (multivitamins) since June 2014.
      DIAGNOSES: Drug-induced liver injury (DILI) and alcoholic fatty liver disease
      (AFLD) were initially considered because the patient had a history of using
      health products (HP) and dietary supplements (DS) and drinking alcohol. However,
      he was subsequently considered with PBC based on the findings of anti
      mitochondrial antibody positivity and elevated immunoglobulin level. Obstructive
      jaundice and space-occupying lesion in the liver were excluded by imaging
      examinations. Liver biopsy was performed to confirm the reasons for liver injury.
      Histopathological examination was conducted, and the patient was diagnosed with
      PBC associated with DILI and alcoholic liver fibrosis. INTERVENTIONS:
      Ursodeoxycholic acid, glycyrrhizic acid, and methylprednisolone (small dose) were
      used to treat the patient. OUTCOMES: After 2 months, the serum levels of ALT,
      AST, AKP, GGT, and globulin returned to normal. After 4 months, the patient
      showed liver injury once again (an increase in ALT, AST, AKP, GGT and GLB) caused
      by repaglinide administration due to hyperglycemia. Ursodeoxycholic acid and
      methylprednisolone replaced the repaglinide administration. After 3 weeks, the
      levels of ALT, AST, AKP, GGT, and GLB returned to normal again. LESSONS: The
      correct knowledge on PBC and early-stage recognition and diagnosis should be
      emphasized. When other causes of the liver injury cannot be excluded, liver
      biopsy is suggested. Histopathological change can be used to further clarify the
      reasons for liver injury and the principal contradiction as well as to guide the
      theraputic regimen.

PMID- 30213009
TI  - The different association of allocentric and egocentric neglect with dorsal and
      ventral pathways: A case report.
AB  - RATIONALE: Egocentric neglect is characterized by responses missing on the
      contralateral side with respect to the viewer, while allocentric neglect is
      characterized in responses missing on the contralateral side with respect to the
      object . However, little has been reported about the neural tracts associated
      with egocentric and allocentric neglect. We investigated which neural tracts were
      involved in two types of neglect (egocentric and allocentric) in a stroke patient
      who showed allocentric neglect by using the Apple Cancellation test, a
      specialized test to distinguish between egocentric and allocentric neglect.
      PATIENT CONCERNS: He showed good cognitive function but presented with severe
      neglect on the left side (A 42-year-old, right-handed male patient). He was
      unable to undergo even the pencil and paper test for evaluation of the severity
      of neglect. DIAGNOSES: He was diagnosed as spontaneous intracerebral hemorrhage
      at the right basal ganglia and underwent conservative management at the
      neurosurgery department of a university hospital. INTERVENTIONS: Two weeks after
      onset, he began rehabilitation at the rehabilitation department of the same
      university hospital. During a seven month rehabilitation, the patient showed
      significant improvement of his severe left neglect. OUTCOMES: We used the Apple
      Cancellation test to distinguish between egocentric and allocentric neglect; the
      results failed to reveal egocentric neglect, however, they did reveal severe
      allocentric neglect. In addition, on diffusion tensor tractography (DTT) at 2
      weeks after onset, the right superior longitudinal fasciculus (SLF) showed
      partial injury and narrowing in the parietal lobe compared to that of the left
      SLF. In addition, the right inferior fronto-occipital fasciculus (IFOF) was not
      reconstructed. By contrast, on 7-month post-onset DTT, the right SLF revealed
      elongation and thickening in the parietal lobe that approached similarity to that
      for the left SLF. However, the right IFOF was still not reconstructed. LESSONS:
      The associations of egocentric neglect with the dorsal pathway (SLF) and the
      association of allocentric neglect with the ventral pathway (IFOF) in the right
      hemisphere were demonstrated in a stroke patient. It appears that DTT can be
      helpful in demonstrating both the affected pathway and the neglect type in
      patients with neglect.

PMID- 30213011
TI  - Clinical presentation and treatment of cardiac myxoma in 153 patients.
AB  - Cardiac myxoma (CM) is the most common benign cardiac tumor. We retrospectively
      reviewed our single center experience in 153 patients with CM over a period 25
      years.From November 1993 to May 2017, 153 patients were operated in our
      institution with diagnosis of a CM. In all patients preoperative, perioperative,
      and postoperative data were recorded including the long-term follow-up. All
      patients followed up in the outpatient's clinics and echocardiography at regular
      intervals.Mean age 59 +/- 12 years old. There were 104 women and 49 men.
      Preoperative clinical manifestations of the patients were hemodynamic
      consequences (47.7%), asymptomatic (46.4%), systemic embolism (4.5%), systemic
      manifestations-fever (0.7%), and hemoptysis (0.7%). The most common location of
      CM was in the left atrium in 82.4% patients. Mean tumors diameter was 4.5 +/- 1.9
      cm. In addition, we were observed that the age of the patients have differences
      between sex groups women versus men, 60.3 and 54.8 years old respectively (P =
      .02). On the other hand the tumor size have not differences between the sex
      groups (P = .56). Combine operations were performed in 24 (15.7%) patients. New
      cerebrovascular accident was observed in 2 patients post-op. Mean in-hospital
      stay was 8.02 +/- 2.8 days. In-hospital mortality was 1 patient (0.7%) (from
      sepsis). During median follow-up 3.7 +/- 4.3 years CM recurrence was identified
      in 5 (3.3%) patients.Surgical resection of CMs contributes in an excellent
      prognosis and associated with low complications and recurrences rate. Regular
      long-term follow-up is recommended in all patients with CM.

PMID- 30213013
TI  - A meta-analysis of surgical decompression in the treatment of diabetic peripheral
      neuropathy.
AB  - BACKGROUND: Over the last decade, surgical decompression procedures have been
      commonly used in the treatment of diabetic peripheral neuropathy (DPN). However,
      the effectiveness of them remains to be proved. METHODS: A comprehensive
      literature search of databases including PubMed-Medline, Ovid-Embase, and
      Cochrane Library was performed to collect the related literatures. The Medical
      Subject Headings used were "diabetic neuropathy," "surgical decompression," and
      "outcomes." The methodological index for nonrandomized studies was adopted for
      assessing the studies included in this review. Analyses were performed with
      Review Manager (Version 5.3, The Nordic Cochrane Centre, the Cochrane
      Collaboration, Copenhagen, 2014). RESULTS: A total of 12 literatures (including 8
      prospective and 4 retrospective) encompassing 1825 patients with DPN were
      included in the final analysis. Only 1 literature was identified as a randomized
      controlled trial. The remaining 11 literatures were observational studies; 7 of
      them were classified as upper-extremity nerve decompression group and 4 of them
      were classified as lower-extremity nerve decompression group. Meta-analysis shows
      that Boston questionnaire symptom severity and functional status of upper
      extremities, and distal motor latency and sensory conduction velocity of median
      nerve of DPN patients are significantly improved after carpal tunnel release.
      Besides, visual analog scale and 2-point discrimination are considered clinically
      and statistically significant in lower extremities after operation. CONCLUSIONS:
      The findings from our review have shown the efficacy of surgical decompression
      procedures in relieving the neurologic symptoms and restoring the sensory
      deficits in DPN patients. As there are few high-quality randomized-controlled
      trials or well-designed prospective studies, more data are needed to elucidate
      the role of surgical procedures for DPN treatment in the future.

PMID- 30213012
TI  - Efficacy and safety of combined high-dose interferon and red light therapy for
      the treatment of human papillomavirus and associated vaginitis and cervicitis: A
      prospective and randomized clinical study.
AB  - BACKGROUND: We evaluated the efficacy and safety of combined high-dose interferon
      (IFN) and red light therapy for the treatment of subclinical and latent human
      papillomavirus (HPV) infections. METHODS: Ninety women diagnosed with subclinical
      or latent HPV infection were randomized to receive topical application of low
      dose recombinant IFNalpha-2b (1 million IU), high-dose IFNalpha-2b (9 million
      IU), or a combination of high-dose IFNalpha-2b and red light therapy on the
      cervix and vagina. All patients received treatment once daily for 4 weeks. HPV
      titer was measured immediately and 4, 8, and 12 weeks after treatment to
      determine the rates of viral clearance and infection cure. Treatment of HPV
      associated vaginitis and cervicitis was also evaluated. RESULTS: Results showed
      that immediately and 4, 8, and 12 weeks after treatment, the HPV clearance rates
      and infection cure rates were higher in the high-dose IFN and combination groups
      compared to the low-dose IFN group. High-dose IFN and combination therapies were
      significantly effective against both low-risk and high-risk HPV infections.
      Although the cure rates for vaginitis and cervicitis were significantly higher in
      the high- compared to the low-dose IFN group, rates were even higher in the
      combination group compared to the high-dose IFN group. Mild adverse effects were
      reported by a very small subset of patients (3/30) in the combination group.
      CONCLUSIONS: This study suggests that combination of high-dose IFN and red light
      therapy is safe and effective against subclinical and latent HPV infections.

PMID- 30213014
TI  - Effectiveness of 3-dimensional shoulder ultrasound in the diagnosis of rotator
      cuff tears: A meta-analysis.
AB  - BACKGROUND: Numerous quantitatively based studies measuring the accuracy of 3D
      shoulder ultrasound (US) for the diagnosis of rotator cuff tears remain
      inconclusive. In order to determine how effective 3D shoulder US is for detecting
      rotator cuff tears, a meta-analysis was performed systematically. METHODS: Six
      electronic databases, PubMed/Medline, Embase, Cochrane Library, CNKI, VIP data,
      and Wanfang data, were utilized to retrieve articles praising the diagnostic
      value of 3D shoulder US for use in detecting rotator cuff tears. After screening
      and diluting out the articles that met inclusion criteria to be used for
      statistical analysis, the pooled evaluation indexes including sensitivity,
      specificity, and diagnostic odds ratio (DOR) as well as the summary receiver
      operating characteristic curve (SROC) were calculated utilizing Meta-Disc v.1.4.
      RESULTS: Screening determined that out of 4220, 7 studies involving a total of
      282 patients were deemed viable for inclusion in the meta-analysis. The results
      of the analysis showed that the sensitivity and specificity were at 94% and 83%,
      respectively, with a DOR of 60.06, Q* index of 0.9058 and the area under SROC of
      0.9609. Additionally, a satisfactory accuracy of 3D shoulder US was observed in
      detecting full- and partial-thickness rotator cuff tears. CONCLUSION: This meta
      analysis suggests that 3D shoulder US is very effective and highly accurate to
      detect full-thickness rotator cuff tears, but may lack accuracy in the diagnosis
      of partial tears.

PMID- 30213015
TI  - Utilization of extracorporeal membrane oxygenation for a severe cardiocirculatory
      dysfunction recipient in liver transplantation: A case report.
AB  - RATIONALE: Severe cardiac dysfunction or severe pulmonary hypertension is a
      contraindication of liver transplantation (LT). Extracorporeal membrane
      oxygenation (ECMO) is an advanced therapy for severe lung and/or
      cardiocirculatory dysfunction or failure. The application of ECMO to patients
      during the LT perioperative period may help recipients with severe cardiac
      disease to maintain the heart function and alleviate the reperfusion syndrome.
      PATIENT CONCERNS: A female liver recipient complained about weakness for 6
      months. DIAGNOSES: The patient was diagnosed as hepatitis B virus (HBV)-related
      hepatic cirrhosis (MELD 24, Child-Pugh C) with severe mitral regurgitation,
      severe tricuspid regurgitation, left atrium and left ventricle enlargement,
      cardiac insufficiency, pulmonary arterial hypertension, and hypoxemia.
      INTERVENTIONS: The patient underwent LT from a cardiac deceased donor. The
      surgery was completed by venoarterial ECMO. The femoral vessels cannulation was
      done after the dissection of the patient's liver and before the venous blocking.
      Venous cannula reached to the position below renal vein, while arterial cannula
      reached to common iliac artery. We regulated the ECMO index according to the
      patient's condition. The dosage of heparin was adjusted on the basis of the
      activated clotting time. Respiratory support, milrinone, furosemide, and mannitol
      were used to improve the circulation. The bleeding volume of surgery was 1200 mL.
      The cardiocirculatory function and other vital signs remained good in the
      perioperative period. In the first 24 hours after surgery, central venous
      pressure decreased from 17 to 7 cmH2O. Thirty hours after surgery, the ECMO was
      removed. Eighteen hours later, the recipient did not need respiratory support.
      OUTCOMES: No complications of transplantation or ECMO were found. LESSONS: It is
      feasible to utilize ECMO as a cardiocirculatory function support in the LT. ECMO
      does not increase the risk of hemorrhage. ECMO can play an important role in
      ensuring the security of the liver recipients in the surgery and in the
      postoperative period.

PMID- 30213017
TI  - Favorable remodeling after hybrid arch debranching and modified provisional
      extension to induce complete attachment technique in type a aortic dissection: A
      case report.
AB  - RATIONALE: Type A aortic dissection (TAAD) usually requires emergency open repair
      of the ascending aorta. In cases of diffuse dissection that spreads along the
      descending and abdominal aorta (type I, DeBakey classification), the risk of
      aneurysmal degeneration varies between 30% and 50% during 5 years and increases
      even higher during a longer follow-up. Those patients might require complex
      intervention to prevent aortic rupture. A combination of hybrid arch debranching
      and the extended provisional extension to induce complete attachment (e
      PETTICOAT) technique might be an available alternative in such cases. This is the
      first report of the successful use of the e-PETTICOAT technique for treating
      degenerative, diffuse TAAD. PATIENT CONCERNS: Acute chest pain and syncope were
      the initial symptoms of diffuse TAAD in our 66-year-old female patient. Open
      replacement of the ascending aorta followed by surgical arch debranching was
      performed as a staged procedure. Unfortunately, progressive aneurysmal
      degeneration was revealed 6 months later in the thoracic, abdominal, and
      infrarenal aorta with the recurrence of chest and lumbar pain. DIAGNOSES:
      Computed angiotomography revealed severe aneurysmal degeneration of aortic
      dissection in the thoracic and abdominal aorta. INTERVENTION: The e-PETTICOAT
      enabled good remodeling and stopped degeneration. OUTCOME: At the 2-year follow
      up, good remodeling with complete false lumen thrombosis and a stable aortic size
      were confirmed. LESSON: Lifelong follow-up in extensive TAAD should be
      considered. The e-PETTICOAT technique is an available alternative to fenestrated
      endovascular aortic repair for degenerative TAAD, as it promotes favorable
      remodeling after successful surgery of the ascending aorta.

PMID- 30213016
TI  - Treatment of primary hepatic neuroendocrine tumors with associating liver
      partition and portal vein ligation for staged hepatectomy (ALPPS): A case report
      and literature review.
AB  - RATIONALE: Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare and
      are difficult to diagnose preoperatively.We report a case of PHNET diagnosed
      preoperatively and successfully resected using associating liver partition and
      portal vein ligation for staged hepatectomy (ALPPS). PATIENT CONCERNS: A 72-year
      old woman was admitted to our hospital for a hepatic mass, which was incidentally
      identified during a routine health checkup. The patient has no other obvious
      symptoms of discomfort. DIAGNOSES: Physical examination revealed a palpable mass
      in the right upper quadrant of her abdomen. Dynamic contrast-enhanced abdominal
      computed tomography (CT) showed a low-density mass measuring 13 * 7 * 6 cm in
      both, the right and left hepatic lobes. F-fluorodesoxyglucose positron emission
      tomography (F-FDG PET) and fused PET/CT showed increased uptake by the mass,
      which was indicative of a hepatic tumor. INTERVENTIONS: We use a novel ALPPS
      surgical procedure to safely and radically remove primary neuroendocrine tumors.
      OUTCOMES: No postoperative bleeding and bile leakage were reported, and the
      patient recovered uneventfully.The patient was followed-up for a year without
      recurrence. LESSONS: PHNETs are rare tumors, and confirming the diagnosis using
      the best possible preoperative examination is important. An optimal treatment
      plan is selected based on the patient's condition to ensure a favorable
      prognosis. Tumors too large to undergo surgical removal can be resected using the
      ALPPS procedure, as described in this case report.

PMID- 30213018
TI  - Treatment of a symptomatic cervical perineural cyst with ultrasound-guided
      cervical selective nerve root block: A case report.
AB  - RATIONALE: Symptomatic cervical perineural cysts are extremely rare, and they
      cause radicular pain by compressing the cervical nerve root. Several methods have
      been applied to manage the radicular pain induced by cervical perineural cysts,
      including medication, percutaneous procedures, and surgery. However, these
      methods are associated with various outcomes and complications. The percutaneous
      procedure is simple and easy to perform, but if the perineural cyst wall is
      punctured, it can lead to secondary complications, which include aseptic
      meningitis and intracranial hypotension. PATIENT CONCERNS: A 51-year-old woman
      presented with a dull pain in the left shoulder and a tingling sensation in the
      left dorsal arm, hand, and middle finger. DIAGNOSIS: The patient was diagnosed
      with left C7 radicular pain caused by a perineural cyst. INTERVENTIONS: The left
      C7 radicular pain did not respond to treatment with medication. Therefore, a left
      C7 nerve root block with local anesthetics and steroids was performed under
      ultrasound guidance. Adjunctively, real-time fluoroscopy with contrast was used
      to avoid intravascular injection. OUTCOME: The symptoms resolved without any
      complications. LESSONS: In this case, perineural cyst-induced radicular pain,
      which was resistant to medication, was treated using ultrasound guided cervical
      selective nerve root block with local anesthetics and steroids. Ultrasound
      guidance can enable successful cervical selective nerve root block without
      perineural cystic wall puncture. Therefore, ultrasound-guided cervical nerve root
      block is an effective treatment option for radicular pain caused by a symptomatic
      perineural cyst.

PMID- 30213019
TI  - Mixed cryoglobulinemic membranoproliferative glomerulonephritis due to monoclonal
      gammopathy of undetermined significance: A case report.
AB  - RATIONALE: Membranoproliferative glomerulonephritis (MPGN) can be induced by
      autoimmune diseases, chronic infection, chronic hepatitis, and paraproteins
      (including cryoglobulinemia). In addition, the mixed cryoglobulinemic MPGN is
      reported to be highly correlated with hepatitis C virus (HCV) infection. PATIENT
      CONCERNS: We reported a rare case of a 61-year-old woman without a history of
      viral hepatitis infection; she presented with bilateral leg edema and
      proteinuria. Renal pathology revealed MPGN with multiple positive
      immunofluorescent staining. The consequent serum survey revealed positive
      cryoglobulin and monoclonal gammopathy of kappa type of immunoglobulin M.
      However, bone marrow study showed no obvious plasma cell proliferation,
      indicating that multiple myeloma was less likely. DIAGNOSES: This patient's
      cryoglobulinemic MPGN could be related to monoclonal gammopathy of undetermined
      significance. INTERVENTIONS: Oral immunosuppressant. OUTCOMES: After steroid
      treatment, her renal function normalized and proteinuria kept in low level.
      LESSONS: We demonstrated a rare cause of cryoglobulinemic MPGN without HCV
      infection, which led to a favorable prognosis after receiving steroid therapy.
      Moreover, the diagnosis of monoclonal gammopathy should be considered when facing
      such case and aggressive steroid therapy might be beneficial.

PMID- 30213020
TI  - Validation of the Chinese version of the Mini Sarcopenia Risk Assessment
      questionnaire in community-dwelling older adults.
AB  - A new sarcopenia screening tool named Mini Sarcopenia Risk Assessment (MSRA) has
      recently been developed, which showed a reasonable sensitivity and specificity.We
      cross-culturally adapted and validated the Chinese version of the MSRA in a
      population of community-dwelling older adults.We conducted a cross-sectional
      study in a community in Chengdu, China. Older adults aged 60 years or older were
      included. A Chinese translation of the MSRA was created. The Chinese version of
      the MSRA included 2 questionnaires named C-MSRA-7 (containing 7 items) and C-MSRA
      5 (containing 5 items). For C-MSRA-7 and C-MSRA-5, total scores of <= 30 and 45,
      respectively, indicate that the subject has sarcopenia. Using 4 common diagnostic
      criteria of sarcopenia (the European Working Group on Sarcopenia in Older People,
      Asia Working Group for Sarcopenia, International Working Group on Sarcopenia, and
      Foundation for the National Institutes of Health criteria) as the "gold
      standard"; the sensitivity and specificity of the C-MSRA-7 and C-MSRA-5 were
      examined. We applied the receiver operating characteristic curve to compare the
      overall accuracy of the C-MSRA-7 and C-MSRA-5 for screening sarcopenia.We
      recruited 384 participants (mean age: 71.5 +/- 5.8 years). Using different
      criteria as the "gold standard," both C-MSRA-7 and C-MSRA-5 have acceptable
      sensitivity (ranging from 78.0% [95% confidence interval [CI]: 66.3-87.7] to
      86.9% [95% CI: 75.87-94.2] for C-MSRA-7 and from 80.2% [95% CI: 70.8-87.6] to
      90.2% [95% CI: 79.8-96.3] for C-MSRA-5) for screening sarcopenia. However,
      compared with the C-MSRA-7, the C-MSRA-5 is simpler and has better specificity
      (ranging from 55.9% to 70.6% for C-MSRA-5; and 38.3% to 41.0% for C-MSRA-7) and
      overall diagnostic accuracy.The MSRA scale was successfully adapted to the
      Chinese language and validated in Chinese community-dwelling older adults.
      Compared with C-MSRA-7, C-MSRA-5 is the better tool for screening sarcopenia.

PMID- 30213021
TI  - Validation of same-day bowel preparation regimen using 4L polyethylene glycol:
      Comparison of morning and afternoon colonoscopy.
AB  - A split-dose regimen is the recommended method of bowel preparation for
      colonoscopy. However, for colonoscopy performed in the afternoon, same-day
      preparation is recommended rather than a split-dose regimen. No study has
      compared the efficacy of same-day bowel-cleansing for morning colonoscopy (MC)
      and afternoon colonoscopy (AC). The aims of this study were to evaluate the bowel
      cleansing efficacy, adverse events, and patient tolerability of same-day bowel
      preparation for colonoscopy using 4L polyethylene glycol (PEG).The medical
      records of consecutive patients who underwent colonoscopy at our healthcare
      center over 3 months were retrospectively reviewed. Colonoscopy was performed
      between 10:00 and 16:00. Study subjects were assigned to the MC or AC group
      according to their colonoscopy start time (MC group, before 12:00; AC group,
      after 12:00). Study subjects were instructed to drink 500-mL PEG every 15
      minutes. In the MC group, bowel cleansing was started at 05:00 and finished at
      07:00. For the AC group, 2L PEG was consumed from 07:00, and the remaining 2L PEG
      was started 3 hours before colonoscopy. The composite safety profile included
      vital signs, laboratory test results, and questionnaire findings. Laboratory
      testing of subjects and completion of the questionnaire were performed before
      colonoscopy. The questionnaire asked about adverse events and tolerability of the
      bowel cleansing regimen. Bowel-cleansing efficacy was assessed using the Boston
      bowel preparation scale (BBPS). Bowel-cleansing efficacy, tolerability, and
      safety profile were compared between the 2 groups.Two hundred and ninety-one
      subjects were included (MC group, 169; AC group, 122).The BBPS did not differ
      between the 2 groups (7.3 +/- 0.8 vs. 7.3 +/- 0.8, P = .68). There were no
      instances of electrolyte imbalance or hemodynamic instability in either group.
      The tolerability of the bowel-cleansing regimen did not differ between the 2
      groups (P = .59).The bowel-cleansing efficacy, safety profile, and patient
      tolerability of MC and AC were comparable. A same-day dose of 4L PEG is a
      feasible bowel preparation method.

PMID- 30213023
TI  - Meta-analysis of the efficacy of Ningmitai capsule on the treatment of chronic
      prostatitis in China: Erratum.

PMID- 30213022
TI  - Treatment variation related to comorbidity and complications in type 2 diabetes:
      A real world analysis.
AB  - A complex comorbidity status may cause treatment variance interfering with type 2
      diabetes (T2D) guideline-confirm therapy and influence the occurrence of
      complications but evidence on its relationships and alternative treatments are
      lacking. This study aimed to identify treatment variance and common T2D drug
      treatment related to comorbid status and the association with comorbidity and
      complications.Based on Korean National Health Insurance Service-National Sample
      Cohort (NHIS-NSC) databases, we conducted a retrospective, observational
      exploratory study including 7123 T2D patients without microvascular-,
      macrovascular complication. We explored patterns of comorbid status and drug
      treatment and its relation to the development of complications within 4-year
      period. Analysis was performed by two-step cluster analysis and nonlinear
      canonical correlation analysis.64.9% had at least one other chronic disease and
      61.7% of T2D patients were treated with >1 glucose lowering drugs. 15.8%
      developed microvascular complications and 6.5% had ischemic heart disease or
      cerebrovascular complications. 82.2% of the treatment patterns were identified
      among T2D patients with 1 or no comorbidity while 14.4% was identified in
      patients with >=2 comorbidities. Combination treatment such as, sulfonylurea or
      dipeptidyl peptidase-4 inhibitors combined with metformin were observed.
      Occurrence of microvascular- or/and macrovascular complication and its relation
      to comorbidity and treatment pattern was not identified.In conclusion, as number
      of comorbidity increased with both type of comorbidity (diabetes related-,
      unrelated) present, common treatment patterns were less or not identified. More
      treatment variance was observed in patient's groups that had developed
      complications.

PMID- 30213024
TI  - A randomized controlled trial for effectiveness of zolpidem versus acupressure on
      sleep in hemodialysis patients having chronic kidney disease-associated pruritus:
      Erratum.

PMID- 30213026
TI  - Epigenetics of Neurodevelopmental Disorders Comes of Age with Roles in Clinical
      and Educational Applications.
AB  - Epigenetics is a gene regulation mechanism that does not depend on genomic DNA
      sequences, but depends instead on chemical modifications of DNA and histone
      proteins. [...].

PMID- 30213027
TI  - No Increase in Colon Cancer Risk Following Induction with Neu5Gc-Bearing Rabbit
      Anti-T Cell IgG (ATG) in Recipients of Kidney Transplants.
AB  - Because of a mutation of the gene allowing the synthesis of the Neu5Gc form of
      neuraminidic acid, humans lack the Neu5Gc present in other mammals and develop
      anti-Neu5Gc. However, humans can absorb dietary Neu5Gc and normal colon
      epithelium displays minute amounts of Neu5Gc. The potential "physiological"
      formation of in situ immune complexes has been proposed as a risk factor for
      colon cancer and as the link between red meat-rich diet and colon carcinoma. In
      this article, we took advantage of evidence that polyclonal rabbit IgG (ATG)
      elicits an immune response against Neu5Gc and we consulted a large data base of
      allograft recipients treated or not with animal-derived IgG to discuss this
      hypothesis. Based on data from 173,960 and 38,505 patients without and with ATG
      induction, respectively, we found no evidence that exposure to higher levels of
      anti-Neu5Gc is associated with a higher incidence of colon carcinoma.

PMID- 30213025
TI  - Tanshinone IIA Attenuates Insulin Like Growth Factor 1 -Induced Cell
      Proliferation in PC12 Cells through the PI3K/Akt and MEK/ERK Pathways.
AB  - The insulin like growth factor 1 (IGF-1) and its receptor (IGF-1R) facilitate
      tumor proliferation and progression. Tanshinone IIA (TSN) is an active diterpene
      quinone isolated from the roots of the herbal plant Salvia miltiorrhiza. TSN
      inhibits the proliferation of various types of cancer cells but its role in the
      IGF-1R-induced proliferation of pheochromocytoma (PC12) cells and the potential
      mechanisms are largely unknown. This study aims to investigate the anti
      proliferative effect of TSN in PC12 cells and its role on IGF-1R signaling
      transduction. PC12 cells were treated with IGF-1 with or without TSN, methyl
      thiazolytetrazolium (MTT) assay, and cell counting kit-8 and flow cytometry were
      used to evaluate the proliferation of PC12 cells. The role of TSN on the
      apoptosis of PC12 cells were detected by flow cytometry as well. The effects of
      TSN and IGF-1 on the phosphorylation of IGF-1R, protein kinase B (Akt),
      extracellular-signal related kinase 1/2 (ERK1/2) and other downstream targets
      were analyzed by Western blotting analysis. Our results showed that IGF-1
      promoted the growth of PC12 cells in a dose-dependent manner and increased the
      phosphorylation of IGF-1R, whereas TSN attenuated the effect of IGF-1.
      Interestingly, TSN did not induce cell apoptosis in PC12 cells. Moreover, TSN
      attenuated the phosphorylation of Akt and ERK1/2 induced by IGF-1, and the
      phosphorylation of glycogen synthase kinase-3beta, forkhead box O3a (FOXO3a) and
      c-Raf were also inhibited by TSN. Furthermore, TSN inhibited cell growth induced
      by IGF-1 and blocked the activation of IGF-1R in SH-SY5Y cells. Taken together,
      TSN has an inhibitory effect on the proliferation of PC12 cells via down
      regulation of the phosphorylated IGF-1R and its downstream signaling.

PMID- 30213028
TI  - DOA Estimation for Coprime Linear Array Based on MI-ESPRIT and Lookup Table.
AB  - In order to improve the angle measurement performance of a coprime linear array,
      this paper proposes a novel direction-of-arrival (DOA) estimation algorithm for a
      coprime linear array based on the multiple invariance estimation of signal
      parameters via rotational invariance techniques (MI-ESPRIT) and a lookup table
      method. The proposed algorithm does not require a spatial spectrum search and
      uses a lookup table to solve ambiguity, which reduces the computational
      complexity. To fully use the subarray elements, the DOA estimation precision is
      higher compared with existing algorithms. Moreover, the algorithm avoids the
      matching error when multiple signals exist by using the relationship between the
      signal subspace of two subarrays. Simulation results verify the effectiveness of
      the proposed algorithm.

PMID- 30213029
TI  - Effects of Sensor Location on Dynamic Load Estimation in Weigh-in-Motion System.
AB  - In recent years, weigh-in-motion systems based on embedded sensor networks have
      received a lot of attention. However, how to improve the accuracy of multi-sensor
      weigh-in-motion (WIM) systems while keeping costs low remains a challenge. In
      this paper, a numerical simulation method is presented to analyze the
      relationship between sensor location and the accuracy of static weight
      estimation. The finite element model of a WIM system is developed, which consists
      of three parts: a pavement model, a moving load model and two types of sensor
      models. Analysis of simulation results shows that the ability of sensing dynamic
      load is closely related to the installation depth of sensors and pavement
      material. Moreover, the distance between the moving wheel and sensors has a great
      impact on estimating performance. Gaussian curve fitting could be used to reduce
      weighing error within a limited range. Our work suggests that much more attention
      should be paid to the design of the sensor layout of a WIM system.

PMID- 30213030
TI  - Development of a Surface Temperature Sensor to Enhance Energy Efficiency Actions
      in Buildings.
AB  - The air temperature increase in urban centers can lead to problems such as
      increased energy consumption associated to air conditioning, the intensification
      of pollution, human discomfort and health problems. In this context, the building
      envelope plays an important role in urban thermal equilibrium. Energy efficiency
      rating systems for buildings (LEED-Leadership in Energy and Environmental Design,
      AQUA-High Environmental Quality, PROCEL Edifica, etc.) stimulate energy
      efficiency actions in the built environment, considering, for example, the
      envelope and energy efficiency initiatives in buildings. Research carried out
      recently has shown that monitoring of buildings can provide important information
      about building performance, supporting building control strategies and enabling
      actions aimed at improving energy efficiency and thermal comfort. More
      specifically, wireless sensors are also being used to monitor buildings. This
      work proposes and presents the development of a surface temperature sensor that
      can support actions to enhance energy efficiency in the built environment,
      meeting the requirements proposed by the energy efficiency rating systems of
      buildings. This sensor must have characteristics such as low cost, the storage
      capacity of a large amount of data and the possibility of remote monitoring of
      the collected temperatures. Computer simulations and validation tests were
      carried out showing that the proposed sensor allows the remote monitoring (using
      a wireless transmission system) of the surface temperature in buildings,
      respecting the requirements of high storage capability and low cost.

PMID- 30213031
TI  - An All-Organic Flexible Visible Light Communication System.
AB  - Visible light communication systems can be used in a wide variety of
      applications, from driving to home automation. The use of wearables can increase
      the potential applications in indoor systems to send and receive specific and
      customized information. We have designed and developed a fully organic and
      flexible Visible Light Communication system using a flexible OLED, a flexible
      P3HT:PCBM-based organic photodiode (OPD) and flexible PCBs for the emitter and
      receiver conditioning circuits. We have fabricated and characterized the I-V
      curve, modulation response and impedance of the flexible OPD. As emitter we have
      used a commercial flexible organic luminaire with dimensions 99 * 99 * 0.88 mm,
      and we have characterized its modulation response. All the devices show frequency
      responses that allow operation over 40 kHz, thus enabling the transmission of
      high quality audio. Finally, we integrated the emitter and receiver components
      and its electronic drivers, to build an all-organic flexible VLC system capable
      of transmitting an audio file in real-time, as a proof of concept of the indoor
      capabilities of such a system.

PMID- 30213033
TI  - Fabrication of Dielectric Elastomer Composites by Locking a Pre-Stretched Fibrous
      TPU Network in EVA.
AB  - Dielectric elastomer (DE) composites with high electrical breakdown strength and
      large voltage-induced deformation were developed by retaining pre-stretched
      thermoplastic polyurethane (TPU) fibers in ethylene vinyl acetate copolymer
      (EVA). The microstructure of the candidate E-TPU fiber membrane and EVA coated E
      TPU (E-TPU/EVA) film were characterized by scanning electron microscopy (SEM).
      The quasi-static and dynamic mechanical property, and the electromechanical
      properties, including the dielectric constant, dielectric loss tangent, and
      electromechanical sensitivity, of the DE composites were evaluated. Initially,
      tensile tests demonstrated that the DE composites based on E-TPU/EVAs had a
      higher elongation at break of above 1000% but a low elastic modulus of
      approximately 1.7 MPa. Furthermore, dielectric spectroscopy showed that the E
      TPU/EVA had a dielectric constant of 4.5 at the frequency of 1000 Hz, which was
      1.2 times higher than that of pure EVA film. Finally, it was found from
      electromechanical test that the voltage induced strain of E-TPU/EVA rose to 6%,
      nearly 3 times higher than that of pure TPU film, indicating an excellent
      electromechanical property. The DE composites developed have demonstrated the
      potential to be good candidate materials in the fields of artificial
      intelligence, biomimicry and renewable energy.

PMID- 30213034
TI  - New Multi-Keyword Ciphertext Search Method for Sensor Network Cloud Platforms.
AB  - This paper proposed a multi-keyword ciphertext search, based on an improved
      quality hierarchical clustering (MCS-IQHC) method. MCS-IQHC is a novel technique,
      which is tailored to work with encrypted data. It has improved search accuracy
      and can self-adapt when performing multi-keyword ciphertext searches on privacy
      protected sensor network cloud platforms. Document vectors are first generated by
      combining the term frequency-inverse document frequency (TF-IDF) weight factor
      and the vector space model (VSM). The improved quality hierarchical clustering
      (IQHC) algorithm then generates document vectors, document indices, and cluster
      indices, which are encrypted via the k-nearest neighbor algorithm (KNN). MCS-IQHC
      then returns the top-k search result. A series of experiments proved that the
      proposed method had better searching efficiency and accuracy in high-privacy
      sensor cloud network environments, compared to other state-of-the-art methods.

PMID- 30213032
TI  - In Vivo Genome Editing as a Therapeutic Approach.
AB  - Genome editing has been well established as a genome engineering tool that
      enables researchers to establish causal linkages between genetic mutation and
      biological phenotypes, providing further understanding of the genetic
      manifestation of many debilitating diseases. More recently, the paradigm of
      genome editing technologies has evolved to include the correction of mutations
      that cause diseases via the use of nucleases such as zinc-finger nucleases (ZFN),
      transcription activator-like effector nucleases (TALENs), and more recently, Cas9
      nuclease. With the aim of reversing disease phenotypes, which arise from somatic
      gene mutations, current research focuses on the clinical translatability of
      correcting human genetic diseases in vivo, to provide long-term therapeutic
      benefits and potentially circumvent the limitations of in vivo cell replacement
      therapy. In this review, in addition to providing an overview of the various
      genome editing techniques available, we have also summarized several in vivo
      genome engineering strategies that have successfully demonstrated disease
      correction via in vivo genome editing. The various benefits and challenges faced
      in applying in vivo genome editing in humans will also be discussed.

PMID- 30213035
TI  - Developments in Taste-Masking Techniques for Traditional Chinese Medicines.
AB  - A variety of pharmacologically active substances, including chemotherapeutic
      drugs and the substances from traditional Chinese medicine (TCM), always exhibit
      potent bioactivities after oral administration. However, their unpleasant taste
      (such as bitterness) and/or odor always decrease patient compliance and thus
      compromise their curative efficacies in clinical application. Therefore, the
      developments of taste-masking techniques are of great significance in improving
      their organoleptic properties. However, though a variety of taste-masking
      techniques have been successfully used to mask the unpalatable taste of
      chemotherapeutic drugs, their suitability for TCM substances is relatively
      limited. This is mainly due to the fact that the bitter ingredients existing in
      multicomponent TCM systems (i.e., effective fractions, single Chinese herbs, and
      compound preparations) are always unclear, and thus, there is lack of tailor-made
      taste-masking techniques to be utilized to conceal their unpleasant taste. The
      relevant studies are also relatively limited. As a whole, three types of taste
      masking techniques are generally applied to TCM, including (i) functional masking
      via sweeteners, bitter blockers, and taste modifiers; (ii) physical masking via
      polymer film-coating or lipid barrier systems; and (iii) biochemical masking via
      intermolecular interaction, beta-cyclodextrin inclusion, or ion-exchange resins.
      This review fully summarizes the results reported in this field with the purpose
      of providing an informative reference for relevant readers.

PMID- 30213036
TI  - The Effect of Pain Relief on Daily Physical Activity: In-Home Objective Physical
      Activity Assessment in Chronic Low Back Pain Patients after Paravertebral Spinal
      Block.
AB  - This study evaluates the effect of paravertebral spinal injection (PSI),
      utilizing both subjective and objective assessments in chronic low back pain
      (LBP) associated with facet joint arthrosis over a one-month duration. Subjective
      questionnaires included the visual analogue scale (VAS) for pain, the Oswestry
      Disability Index, the Health Survey SF-12, and the short Falls Efficacy Scale
      International (FES-I). Objective assessments included in-clinic gait and Timed Up
      and Go (TUG) tests using wearable sensors, as well as 48 h daily physical
      activity (DPA) monitored using a chest-worn triaxial accelerometer. Subjective
      and objective measures were performed prior to treatment, immediately after the
      treatment, and one month after the treatment. Eight LBP patients were recruited
      for this study (mean age = 54 +/- 13 years, body mass index = 31.41 +/- 6.52
      kg/m2, 50% males). Results show significant decrease in pain (~55%, p < 0.05) and
      disability (Oswestry scores, ~21%, p < 0.05). In-clinic gait and TUG were also
      significantly improved (~16% and ~18% faster walking and shorter TUG, p < 0.05);
      however, DPA, including the percentage of physical activities (walking and
      standing) and the number of steps, showed no significant change after PSI (p >
      0.25; effect size <= 0.44). We hypothesize that DPA may continue to be truncated
      to an extent by conditioned fear-avoidance, a psychological state that may
      prevent increase in daily physical activity to avoid pain.

PMID- 30213038
TI  - The Happiness, Hardiness, and Humor Styles of Students with a Bachelor's Degree
      in Sport Sciences.
AB  - Happiness, psychological hardiness, and humor ("the 3Hs") are useful ways of
      assessing resilience to stress in positive psychology. The literature analyzing
      their confluence regarding sports is scarce. This study aims to analyze the
      participants' 3H levels and the relationships between those levels and specific
      variables. The Psychological Hardiness Scale (Psikolojik Dayaniklilik Olcegi,
      PDO), the Oxford Happiness Questionnaire Short Form (OHQ-SF), and the Humor
      Styles Questionnaire (HSQ) were used. Students in pedagogical formation training
      during the 2016-2017 fall semester have participated in the study (N = 211).
      Significant differences were found regarding the levels of psychological
      hardiness in relation to gender, type of sport, and years of participation, and,
      in humor types regarding the variables of gender, age, residence and perceived
      income. There were significant differences in all instruments regarding gender.
      Negative relationships were found between the "aggressive humor" and "challenge"
      and "self-commitment" sub-dimensions of PDO, while the relationships were
      positive between "self-enhancing humor" and PDO and OHQ-SF, and between
      "affiliative humor" style and PDO and OHQ-SF. This study enhances the positive
      socio-psychological account in the literature by incorporating the issues of 3H
      and provides an understanding of particularities that may help improve the
      practice of relevant experts and individuals.

PMID- 30213037
TI  - Acute Effects of Dietary Carbohydrate Restriction on Glycemia, Lipemia and
      Appetite Regulating Hormones in Normal-Weight to Obese Subjects.
AB  - Postprandial responses to food are highly dependent on the macronutrient
      composition of the diet. We investigated the acute effects of transition from the
      recommended moderately high carbohydrate (HC) diet towards a carbohydrate-reduced
      high-protein (CRHP) diet on postprandial glycemia, insulinemia, lipemia, and
      appetite-regulating hormones in non-diabetic adults. Fourteen subjects, including
      five males (Mean +/- SD: age 62 +/- 6.5; BMI 32 +/- 7.6 kg/m2; hemoglobin A1c
      (HbA1c) 40 +/- 3.0 mmol/mol; HOMA2-IR 2.1 +/- 0.9) were included in this
      randomized, cross-over study. Iso-caloric diets were consumed for two consecutive
      days with a median wash-out period of 21 days (range 2-8 weeks) between diets
      (macronutrient energy composition: CRHP/HC; 31%/54% carbohydrate, 29%/16%
      protein, 40%/30% fat). Postprandial glucose, insulin secretion rate (ISR),
      triglycerides (TGs), non-esterified fatty acids (NEFAs), and satiety ratings were
      assessed after ingestion of breakfast (Br) and lunch (Lu), and gut hormones and
      glucagon were assessed after ingestion of Br. Compared with the HC diet, the CRHP
      diet reduced peak glucose concentrations (Br 11%, p = 0.024; Lu 11%, p < 0.001),
      glucose excursions (Br 80%, p = 0.20; Lu 85%, p < 0.001), and ISR (Br 31%; Lu
      64%, both p < 0.001) whereas CRHP, as compared with HC, increased glucagon-like
      peptide-1 (Br 27%, p = 0.015) and glucagon values (Br 249%, p < 0.001). NEFA and
      TG levels increased in the CRHP diet as compared with the HC diet after Br, but
      no difference was found after Lu (NEFA Br 22%, p < 0.01; TG Br 42%, p = 0.012).
      Beta-cell glucose sensitivity, insulin clearance, cholecystokinin values, and
      subjective satiety ratings were unaffected. It is possible to achieve a reduction
      in postprandial glycemia and insulin without a deleterious effect on beta-cell
      glucose sensitivity by substituting part of dietary carbohydrate with iso-caloric
      protein and fat in subjects without type 2 diabetes mellitus (T2DM). The
      metabolic effects are more pronounced after the second meal.

PMID- 30213039
TI  - Ex Vivo and in Vivo Study of Sucrosomial(r) Iron Intestinal Absorption and
      Bioavailability.
AB  - The present study aimed to demonstrate that Sideral(r) RM (SRM, Sucrosomial(r)
      Raw Material Iron) is transported across the excised intestine via a biological
      mechanism, and to investigate the effect that this transport route may produce on
      oral iron absorption, which is expected to reduce the gastrointestinal (GI) side
      effects caused by the bioavailability of non-absorbed iron. Excised rat intestine
      was exposed to fluorescein isothiocyanate (FITC)-labeled SRM in Ussing chambers
      followed by confocal laser scanning microscopy to look for the presence of
      fluorescein-tagged vesicles of the FITC-labeled SRM. To identify FITC-labeled SRM
      internalizing cells, an immunofluorescence analysis for macrophages and M cells
      was performed using specific antibodies. Microscopy analysis revealed the
      presence of fluorescein positive particulate structures in tissues treated with
      FITC-labeled SRM. These structures do not disintegrate during transit, and
      concentrate in macrophage cells. Iron bioavailability was assessed by determining
      the time-course of Fe3+ plasma levels. As references, iron contents in liver,
      spleen, and bone marrow were determined in healthy rats treated by gavage with
      SRM or ferric pyrophosphate salt (FP). SRM significantly increased both area
      under the curve (AUC) and clearance maxima (Cmax) compared to FP, thus increasing
      iron bioavailability (AUCrel = 1.8). This led to increased iron availability in
      the bone marrow at 5 h after single dose gavage.

PMID- 30213040
TI  - Low-Cost and Lightweight 3D-Printed Split-Ring Resonator for Chemical Sensing
      Applications.
AB  - In this paper, a microwave cavity resonator is presented for chemical sensing
      applications. The proposed resonator is comprised of a three dimensional (3D)
      split-ring resonator (SRR) residing in an external cavity and capacitively
      coupled by a pair of coaxial probes. 3D-printing technology with polylactic acid
      (PLA) filament is used to build the 3D SRR and cavity. Then, the surfaces of the
      SRR and the inside walls of cavity are silver-coated. The novelty of our proposed
      structure is its light weight and inexpensive design, owing to the utilization of
      low density and low-cost PLA. A Teflon tube is passed through the split-gap of
      the SRR so that it is parallel to the applied electric field. With an empty tube,
      the resonance frequency of the structure is measured at 2.56 GHz with an
      insertion loss of 13.6 dB and quality factor (Q) of 75. A frequency shift of 205
      MHz with respect to the empty channel was measured when deionized water (DIW) was
      injected into the tube. Using volume occupied by the structure, the weight of the
      proposed microwave resonator is estimated as 22.8 g which is significantly
      lighter than any metallic structure of comparable size.

PMID- 30213041
TI  - Characterizing Virulence of the Pyrenophora tritici-repentis Isolates Lacking
      Both ToxA and ToxB Genes.
AB  - The fungus Pyrenophora tritici-repentis (Ptr) causes tan spot of wheat crops,
      which is an important disease worldwide. Based on the production of the three
      known necrotrophic effectors (NEs), the fungal isolates are classified into eight
      races with race 4 producing no known NEs. From a laboratory cross between 86-124
      (race 2 carrying the ToxA gene for the production of Ptr ToxA) and DW5 (race 5
      carrying the ToxB gene for the production of Ptr ToxB), we have obtained some Ptr
      isolates lacking both the ToxA and ToxB genes, which, by definition, should be
      classified as race 4. In this work, we characterized virulence of two of these
      isolates called B16 and B17 by inoculating them onto various common wheat
      (Triticum aestivum L.) and durum (T. turgidum L.) genotypes. It was found that
      the two isolates still caused disease on some genotypes of both common and durum
      wheat. Disease evaluations were also conducted in recombinant inbred line
      populations derived from two hard red winter wheat cultivars: Harry and Wesley.
      QTL mapping in this population revealed that three genomic regions were
      significantly associated with disease, which are different from the three known
      NE sensitivity loci. This result further indicates the existence of other NE-host
      sensitivity gene interactions in the wheat tan spot disease system.

PMID- 30213042
TI  - Supramolecular Networks from Block Copolymers Based on Styrene and Isoprene Using
      Hydrogen Bonding Motifs-Part 2: Dynamic Mechanical Analysis.
AB  - Thermo-reversible supramolecular networks from polyisoprene-block-polystyrene
      block-polyisoprene (ISI) triblock copolymers with short, functionalized
      polyisoprene (PI) blocks were investigated. Functional groups along the PI blocks
      were hydroxyl groups, ester groups with a carboxylic end-group (-O-CO-CH2-CH2
      COOH), and urethane groups with an amine end-group-synthesized from various types
      of diamines-(-O-CO-NH-R-NH2). Dynamic mechanical analysis (DMA) was performed at
      temperatures above Tg of polystyrene (PS) to investigate the influence of the
      different functional groups, the molecular weight, and the composition of the
      triblock copolymers on the materials' properties. Furthermore, comparisons to DMA
      results of diblock copolymers, modified in the same way, will be presented.
      Arising reversible and irreversible processes observed during DMA experiments
      will be compared to results from temperature-dependent Fourier transform infrared
      (FTIR) spectroscopy. For the elaborated systems, the transition from reversible,
      hydrogen-bonded to permanently cross-linked networks was observed at around 150 
      degrees C.

PMID- 30213043
TI  - Wall Thickness of Industrial Multi-Walled Carbon Nanotubes Is Not a Crucial
      Factor for Their Degradation by Sodium Hypochlorite.
AB  - The propensity of multi-walled carbon nanotubes (MWCNTs) for biodegradation is
      important for their safe use in medical and technological applications. Here, we
      compared the oxidative degradation of two samples of industrial-grade MWCNTs-we
      called them MWCNT-d and MWCNT-t-upon their treatment with sodium hypochlorite
      (NaOCl). The MWCNTs had a similar inner diameter but they differed about 2-fold
      in the outer diameter. Electron microscopy combined with morphometric analysis
      revealed the different degradation of the two types of MWCNTs after their
      incubation with NaOCl-the thicker MWCNT-d were damaged more significantly than
      the thinner MWCNT-t. The both types of MWCNTs degraded at the inner side, but
      only MWCNT-d lost a significant number of the outer graphitic layers. Raman
      spectroscopy demonstrated that both MWCNTs had a similar high defectiveness.
      Using energy-dispersive X-ray spectroscopy, we have shown that the more
      degradable MWCNT-d contained the same level of oxygen as MWCNT-t, but more metal
      impurities. The obtained results suggest that the biodegradability of MWCNTs
      depends not only on the wall thickness but also on the defects and impurities.
      Thus, the biodegradability can be regulated by the synthesis conditions or the
      post-synthesis modifications. Such degradation flexibility may be important for
      both medical and industrial applications.

PMID- 30213044
TI  - Status of Retinoids and Carotenoids and Associations with Clinical Outcomes in
      Maternal-Infant Pairs in Nigeria.
AB  - Vitamin A is an essential nutrient in pregnancy, and other carotenoids have been
      independently associated with maternal-infant outcomes. The objective of this
      study was to quantify the status of vitamin A and carotenoids in Nigerian
      maternal-infant pairs at delivery, compare these to a cohort from a developed
      nation, and determine the impact on clinical outcomes. Maternal and cord blood
      samples were collected in 99 Nigerian mother-infant pairs. Concentrations of
      lutein + zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotenes, and
      retinol were measured using HPLC. Descriptive statistics were calculated and
      Spearman coefficients were used to assess correlations between maternal and cord
      measurements; Mann-Whitney tests were used to compare median plasma values
      between dichotomous variables. Linear regression models were used to adjust for
      relevant confounders. A p < 0.05 was considered statistically significant. Thirty
      five percent of mothers had plasma retinol concentrations <=0.70 umol/L; 82% of
      infants had plasma retinol concentrations <=0.70 umol/L at delivery. Maternal and
      infant concentrations of vitamin A compounds were highly correlated and were
      associated with newborn growth and Apgar scores. Despite plasma concentrations of
      pro-vitamin A carotenoids higher than those reported in other populations,
      pregnant Nigerian women have a high prevalence of vitamin A deficiency. As
      vitamin A related compounds are modifiable by diet, future research determining
      the clinical impact of these compounds is warranted.

PMID- 30213045
TI  - A Novel Fingerprint Sensing Technology Based on Electrostatic Imaging.
AB  - In this paper, we propose a new fingerprint sensing technology based on
      electrostatic imaging, which can greatly improve fingerprint sensing distance.
      This can solve the problem of the existing capacitive fingerprint identification
      device being easy to damage due to limited detection distance and a protective
      coating that is too thin. The fingerprint recognition sensor can also be placed
      under a glass screen to meet the needs of the full screen design of the mobile
      phone. In this paper, the electric field distribution around the fingerprint is
      analyzed. The electrostatic imaging sensor design is carried out based on the
      electrostatic detection principle and MEMS (micro-electro-mechanical system)
      technology. The MEMS electrostatic imaging array, analog, and digital signal
      processing circuit structure are designed. Simulation and testing are carried out
      as well. According to the simulation and prototype test device test results, it
      is confirmed that our proposed electrostatic imaging-based fingerprint sensing
      technology can increase fingerprint recognition distance by 46% compared to the
      existing capacitive fingerprint sensing technology. A distance of more than 439
      MUm is reached.

PMID- 30213046
TI  - A Digital Shade-Matching Device for Dental Color Determination Using the Support
      Vector Machine Algorithm.
AB  - In this study, we developed a digital shade-matching device for dental color
      determination using the support vector machine (SVM) algorithm. Shade-matching
      was performed using shade tabs. For the hardware, the typically used intraoral
      camera was modified to apply the cross-polarization scheme and block the light
      from outside, which can lead to shade-matching errors. For reliable experiments,
      a precise robot arm with +/-0.1 mm position repeatability and a specially
      designed jig to fix the position of the VITA 3D-master (3D) shade tabs were used.
      For consistent color performance, color calibration was performed with five
      standard colors having color values as the mean color values of the five shade
      tabs of the 3D. By using the SVM algorithm, hyperplanes and support vectors for
      3D shade tabs were obtained with a database organized using five developed
      devices. Subsequently, shade matching was performed by measuring 3D shade tabs,
      as opposed to real teeth, with three additional devices. On average, more than
      90% matching accuracy and a less than 1% failure rate were achieved with all
      devices for 10 measurements. In addition, we compared the classification
      algorithm with other classification algorithms, such as logistic regression,
      random forest, and k-nearest neighbors, using the leave-pair-out cross-validation
      method to verify the classification performance of the SVM algorithm. Our
      proposed scheme can be an optimum solution for the quantitative measurement of
      tooth color with high accuracy.

PMID- 30213047
TI  - Passive Q-Switching by Cr4+:YAG Saturable Absorber of Buried Depressed-Cladding
      Waveguides Obtained in Nd-Doped Media by Femtosecond Laser Beam Writing.
AB  - We report on laser performances obtained in Q-switch mode operation from buried
      depressed-cladding waveguides of circular shape (100 MUm diameter) that were
      inscribed in Nd:YAG and Nd:YVO4 media by direct writing with a femtosecond laser
      beam. The Q-switch operation was realized with a Cr4+:YAG saturable absorber,
      aiming to obtain laser pulses of moderate (few MUJ) energy at high (tens to
      hundreds kHz) repetition rate. An average power of 0.52 W at 1.06 MUm consisting
      of a train of pulses of 7.79 MUJ energy at 67 kHz repetition rate, was obtained
      from a waveguide realized in a 4.8 mm long, 1.1-at % Nd:YAG ceramics; the pulse
      peak power reached 1.95 kW. A similar waveguide that was inscribed in a 3.4 mm
      long, 1.0-at % Nd:YVO4 crystal yielded laser pulses with 9.4 MUJ energy at 83 kHz
      repetition rate (at 0.77 W average power) and 1.36 kW peak power. The laser
      performances obtained in continuous-wave operation were discussed for each
      waveguide used in the experiments. Thus, a continuous-wave output power of 1.45 W
      was obtained from the circular buried depressed-cladding waveguide inscribed in
      the 1.1-at %, 4.8 mm long Nd:YAG; the overall optical-to-optical efficiency, with
      respect to the absorbed pump power, was 0.21. The waveguide inscribed in the 1.0
      at %, 3.4 mm long Nd:YVO4 crystal yielded 1.85 W power at 0.26 overall optical
      efficiency. This work shows the possibility to build compact laser systems with
      average-to-high peak power pulses based on waveguides realized by a femtosecond
      (fs) laser beam direct writing technique and that are pumped by a fiber-coupled
      diode laser.

PMID- 30213048
TI  - Exfoliation of Hexagonal Boron Nitride (h-BN) in Liquide Phase by Ion
      Intercalation.
AB  - A green approach to prepare exfoliated hexagonal boron nitride nanosheets (h
      BNNS) from commercially pristine h-BN involving a two-step procedure was
      investigated. The first step involves the dispersion of pristine h-BN within an
      aqueous solution containing gelatin and potassium or zinc chloride using a
      sonication method. The second involves the removal of larger exfoliated h-BNNS
      through a centrifugation procedure. The exfoliation was caused not only by the
      sonication effect but also by intercalation of K+ and Zn2+ ions. Transmission
      electronic microscopy, X-ray diffraction and Raman spectroscopy techniques show
      that the obtained h-BNNS generally display a thickness of about a few (2-3)
      layers with an exfoliation efficiency as high as 16.3 +/- 0.4%.

PMID- 30213049
TI  - Conservation Implications of Shifting Gut Microbiomes in Captive-Reared
      Endangered Voles Intended for Reintroduction into the Wild.
AB  - The Amargosa vole is a highly endangered rodent endemic to a small stretch of the
      Amargosa River basin in Inyo County, California. It specializes on a single,
      nutritionally marginal food source in nature. As part of a conservation effort to
      preserve the species, a captive breeding population was established to serve as
      an insurance colony and a source of individuals to release into the wild as
      restored habitat becomes available. The colony has successfully been maintained
      on commercial diets for multiple generations, but there are concerns that colony
      animals could lose gut microbes necessary to digest a wild diet. We analyzed
      feces from colony-reared and recently captured wild-born voles on various diets,
      and foregut contents from colony and wild voles. Unexpectedly, fecal microbial
      composition did not greatly differ despite drastically different diets and
      differences observed were mostly in low-abundance microbes. In contrast, colony
      vole foregut microbiomes were dominated by Allobaculum sp. while wild foreguts
      were dominated by Lactobacillus sp. If these bacterial community differences
      result in beneficial functional differences in digestion, then captive-reared
      Amargosa voles should be prepared prior to release into the wild to minimize or
      eliminate those differences to maximize their chance of success.

PMID- 30213050
TI  - Chaperone-E3 Ligase Complex HSP70-CHIP Mediates Ubiquitination of Ribosomal
      Protein S3.
AB  - In addition to its role in ribosome biogenesis, ribosomal protein S3 (RPS3), a
      component of the 40S ribosomal subunit, has been suggested to possess several
      extraribosomal functions, including an apoptotic function. In this study, we
      demonstrated that in the mouse brain, the protein levels of RPS3 were altered by
      the degree of nutritional starvation and correlated with neuronal apoptosis.
      After endurable short-term starvation, the apoptotic function of RPS3 was
      suppressed by Akt activation and Akt-mediated T70 phosphorylation, whereas after
      prolonged starvation, the protein levels of RPS3 notably increased, and abundant
      neuronal death occurred. These events coincided with ubiquitination and
      subsequent degradation of RPS3, controlled by HSP70 and the cochaperone E3
      ligase: carboxy terminus of heat shock protein 70-interacting protein (CHIP).
      Thus, our study points to an extraribosomal role of RPS3 in balancing neuronal
      survival or death depending on the degree of starvation through CHIP-mediated
      polyubiquitination and degradation.

PMID- 30213052
TI  - Avocado Fruit on Postprandial Markers of Cardio-Metabolic Risk: A Randomized
      Controlled Dose Response Trial in Overweight and Obese Men and Women.
AB  - Avocados are distinctive fruits having both fats and fibers along with various
      micronutrients and bioactive phytochemicals. This study aimed to assess the
      effects of replacing carbohydrate energy in meals with half or whole avocado on
      postprandial indices of metabolic and vascular health. A single-center,
      randomized, controlled, 3-arm, 6 h, crossover study was conducted in
      overweight/obese middle-aged adults (n = 31). Participants consumed energy
      matched breakfast meals containing 0 g (Control), 68 g (Half-A) or 136 g (Whole
      A) fresh Hass avocado on 3 separate occasions. Post-meal glycemic (p < 0.0001),
      insulinemic (p < 0.0001) and flow mediated vasodilation (FMD) responses were
      reduced compared to Control meal (p < 0.01), independent of dose. Nuclear
      magnetic resonance analyses indicated lower concentrations of triglyceride-rich
      lipoproteins and higher concentrations of larger high-density lipoprotein (HDL)
      particles after the Whole-A vs. the Control meal (p = 0.02, p < 0.05,
      respectively). Race/ethnicity influenced sub-class lipoprotein concentrations (p
      < 0.05). Oxidized low-density-lipoproteins, monocyte chemoattractant protein-1,
      and interleukin-6 were not different among meals. Tumor necrosis factor-alpha
      tended to be lower after Whole-A vs. Control meal (p = 0.07). Replacing
      carbohydrate components with avocados in a meal improved FMD, a measure of
      endothelial function, and improved glycemic and lipoprotein profiles in
      overweight/obese adults. The study provides insight on the acute cardio-metabolic
      benefits of incorporating avocados into a meal.

PMID- 30213053
TI  - Synthesis and Antiproliferative Activity of New Cyclodiprenyl Phenols against
      Select Cancer Cell Lines.
AB  - Six new cyclodiprenyl phenols were synthesized by direct coupling of perillyl
      alcohol and the appropriate phenol. Their structures were established by IR, HRMS
      and mainly NMR. Three human cancer cell lines-breast (MCF-7), prostate (PC-3) and
      colon (HT-29)-were used in antiproliferative assays, with daunorubicin and
      dunnione as positive controls. Results described in the article suggest that
      dihydroxylated compounds 2-4 and monohydroxylated compound 5 display selectivity
      against cancer cell lines, cytotoxicity, apoptosis induction, and mitochondrial
      membrane impairment capacity. Compound 2 was identified as the most effective of
      the series by displaying against all cancer cell lines a cytotoxicity close to
      dunnione antineoplastic agent, suggesting that the cyclodiprenyl phenols from
      perillyl alcohol deserve more extensive investigation of their potential
      medicinal applications.

PMID- 30213051
TI  - The Significance of Chondroitin Sulfate Proteoglycan 4 (CSPG4) in Human Gliomas.
AB  - Neuron glial antigen 2 (NG2) is a chondroitin sulphate proteoglycan 4 (CSPG4)
      that occurs in developing and adult central nervous systems (CNSs) as a marker of
      oligodendrocyte precursor cells (OPCs) together with platelet-derived growth
      factor receptor alpha (PDGFRalpha). It behaves variably in different pathological
      conditions, and is possibly involved in the origin and progression of human
      gliomas. In the latter, NG2/CSPG4 induces cell proliferation and migration, is
      highly expressed in pericytes, and plays a role in neoangiogenesis. NG2/CSPG4
      expression has been demonstrated in oligodendrogliomas, astrocytomas, and
      glioblastomas (GB), and it correlates with malignancy. In rat tumors
      transplacentally induced by N-ethyl-N-nitrosourea (ENU), NG2/CSPG4 expression
      correlates with PDGFRalpha, Olig2, Sox10, and Nkx2.2, and with new vessel
      formation. In this review, we attempt to summarize the normal and pathogenic
      functions of NG2/CSPG4, as well as its potential as a therapeutic target.

PMID- 30213054
TI  - New Antibacterial Bagremycins F and G from the Marine-Derived Streptomyces sp.
      ZZ745.
AB  - As part of our research to discover novel bioactive natural products from marine
      microorganisms, five bagremycin analogues, including the previously unreported
      bagremycins F (1) and G (2), were isolated from a marine actinomycete
      Streptomyces sp. ZZ745. The structures of these compounds were determined by
      means of NMR spectroscopic analysis, HRESIMS data, and optical rotation. Both
      bagremycins F (1) and G (2) showed antibacterial activity against Escherichia
      coli, with MIC values of 41.8 and 61.7 MUM, respectively.

PMID- 30213055
TI  - Zinc Oxide Nanoparticles from Waste Zn-C Battery via Thermal Route:
      Characterization and Properties.
AB  - Disposable batteries are becoming the primary sources of powering day-to-day
      gadgets and consequently contributing to e-waste generation. The emerging e-waste
      worldwide is creating concern regarding environmental and health issues.
      Therefore, a sustainable recycling approach of spent batteries has become a
      critical focus. This study reports the detail characterization and properties of
      ZnO nanoparticles recovered from spent Zn-C batteries via a facile thermal
      synthesis route. ZnO nanoparticles are used in many applications including energy
      storage, gas sensors, optoelectronics, etc. due to the exceptional physical and
      optical properties. A thermal treatment at 900  degrees C under an inert
      atmosphere of argon was applied to synthesize ZnO nanoparticles from a spent Zn-C
      battery using a horizontal quartz tube furnace. X-ray diffraction (XRD), selected
      area electron diffraction (SAED) and X-ray photoelectron spectroscopy (XPS)
      results confirmed the formation of crystalline ZnO nanoparticles. Field emission
      scanning electron microscopy (FESEM) and transmission electron microscopy (TEM)
      analysis confirmed that the size of synthesised ZnO particles were less than 50
      nm and mainly composed of sphere shaped nanoparticles. Synthesized ZnO exhibited
      BET surface area of 9.2629 m2/g and showed absorption of light in the UV region.
      Excitation of ZnO by UV light showed photoluminescence in the visible range. This
      study will create an opportunity for potential applications of ZnO nanoparticles
      from spent batteries and will benefit the environment by reducing the volume of e
      waste in landfills.

PMID- 30213056
TI  - Theoretical Calculations for Highly Selective Direct Heteroarylation
      Polymerization: New Nitrile-Substituted Dithienyl-Diketopyrrolopyrrole-Based
      Polymers.
AB  - Direct Heteroarylation Polymerization (DHAP) is becoming a valuable alternative
      to classical polymerization methods being used to synthesize pi-conjugated
      polymers for organic electronics applications. In previous work, we showed that
      theoretical calculations on activation energy (Ea) of the C-H bonds were helpful
      to rationalize and predict the selectivity of the DHAP. For readers' convenience,
      we have gathered in this work all our previous theoretical calculations on Ea and
      performed new ones. Those theoretical calculations cover now most of the widely
      utilized electron-rich and electron-poor moieties studied in organic electronics
      like dithienyl-diketopyrrolopyrrole (DT-DPP) derivatives. Theoretical
      calculations reported herein show strong modulation of the Ea of C-H bond on DT
      DPP when a bromine atom or strong electron withdrawing groups (such as fluorine
      or nitrile) are added to the thienyl moiety. Based on those theoretical
      calculations, new cyanated dithienyl-diketopyrrolopyrrole (CNDT-DPP) monomers and
      copolymers were prepared by DHAP and their electro-optical properties were
      compared with their non-fluorinated and fluorinated analogues.

PMID- 30213057
TI  - Contrasting In Vitro Apatite Growth from Bioactive Glass Surfaces with that of
      Spontaneous Precipitation.
AB  - Body-fluid-exposed bioactive glasses (BGs) integrate with living tissues due to
      the formation of a biomimetic surface layer of calcium hydroxy-carbonate apatite
      (HCA) with a close composition to bone mineral. Vast efforts have been spent to
      understand the mechanisms underlying in vitro apatite mineralization, as either
      formed by direct precipitation from supersaturated solutions, or from BG
      substrates in a simulated body fluid (SBF). Formally, these two scenarios are
      distinct and have hitherto been discussed as such. Herein, we contrast them and
      identify several shared features. We monitored the formation of amorphous calcium
      phosphate (ACP) and its crystallization into HCA from a Na 2 O-CaO-SiO 2 -P 2 O 5
      glass exposed to SBF for variable periods out to 28 days. The HCA growth was
      assessed semi-quantitatively by Fourier transform infrared spectroscopy and
      powder X-ray diffraction, with the evolution of the relative apatite content for
      increasing SBF-exposure periods evaluated against trends in Ca and P
      concentrations in the accompanying solutions. This revealed a sigmoidal apatite
      growth behavior, well-known to apply to spontaneously precipitated apatite. The
      results are discussed in relation to the prevailing mechanism proposed for in
      vitro HCA formation from silicate-based BGs, where we highlight largely
      simultaneous growth processes of ACP and HCA.

PMID- 30213058
TI  - Transcriptional Identification of Related Proteins in the Immune System of the
      Crayfish Procambarus clarkii.
AB  - The freshwater crayfish Procambarus clarkii is an animal model employed for
      physiological and immunological studies and is also of great economic importance
      in aquaculture. Although it is a species of easy husbandry, a high percentage of
      its production is lost annually as a result of infectious diseases. Currently,
      genetic information about the immune system of crustaceans is limited. Therefore,
      we used the abdominal nerve cord from P. clarkii to obtain its transcriptome
      using Next Generation Sequencing (NGS) to identify proteins that participate in
      the immune system. The reads were assembled de novo and consensus sequences with
      more than 3000 nucleotides were selected for analysis. The transcripts of the
      sequences of RNA were edited for annotation and sent to the GenBank database of
      the National Center for Biotechnology Information (NCBI). We made a list of
      accession numbers of the sequences which were organized by the putative role of
      the immune system pathway in which they participate. In this work, we report on
      80 proteins identified from the transcriptome of crayfish related to the immune
      system, 74 of them being the first reported for P. clarkii. We hope that the
      knowledge of these sequences will contribute significantly to the development of
      future studies of the immune system in crustaceans.

PMID- 30213059
TI  - K+ and Rb+ Affinities of the Na,K-ATPase alpha1 and alpha2 Isozymes: An
      Application of ICP-MS for Quantification of Na+ Pump Kinetics in Myofibers.
AB  - The potassium affinities of Na,K-ATPase isozymes are important determinants of
      their physiological roles in skeletal muscle. This study measured the apparent K+
      and Rb+ affinities of the Na,K-ATPase alpha1 and alpha2 isozymes in intact,
      dissociated myofibers obtained from WT and genetically altered mice
      (alpha1S/Salpha2R/R and skalpha2-/-). It also validates a new method to quantify
      cations in intact, dissociated myofibers, using inductively coupled plasma mass
      spectrometry (ICP-MS). Our findings were that: (1) The extracellular substrate
      sites of Na,K-ATPase bind Rb+ and K+ with comparable apparent affinities;
      however; turnover rate is reduced when Rb+ is the transported ion; (2) The rate
      of Rb+ uptake by the Na,K-ATPase is not constant but declines with a half-time of
      approximately 1.5 min; (3) The apparent K+ affinity of the alpha2 isozymes for K+
      is significantly lower than alpha1. When measured in intact fibers of WT and
      alpha1S/Salpha2R/R mice in the presence of 10 uM ouabain; the K1/2,K of alpha1
      and alpha2 isozymes are 1.3 and 4 mM, respectively. Collectively, these results
      validate the single fiber model for studies of Na,K-ATPase transport and kinetic
      constants, and they imply the existence of mechanisms that dynamically limit pump
      activity during periods of active transport.

PMID- 30213060
TI  - Chemical Characterization of Opuntia ficus-indica (L.) Mill. Hydroalcoholic
      Extract and Its Efficiency against Gastrointestinal Nematodes of Sheep.
AB  - Opuntia ficus-indica (L.) Mill. is a xerophylous plant that originated in
      tropical and subtropical America. This plant is popularly known in Brazil as
      "palma forrageira" (cactus pear) and plays a fundamental role in animal
      nutrition, mainly in the Northeastern semi-arid region of the country. The plant
      has several uses since it presents bioactive compounds that confer biological and
      pharmacological properties. In this context, the cactus pear can also be
      considered a potential product to combat parasite infections. The objective of
      this study was to chemically characterize the O. ficus-indica hydroalcoholic
      extract (OFIEOH) and to determine its efficacy against gastrointestinal parasites
      using in vitro tests. Initially, the hydroalcoholic extract from cladode peels of
      O. ficus-indica was produced by maceration for 21 days. For the chemical
      characterization, colorimetric dosages were performed for carbohydrates,
      proteins, phenols and condensed tannins. Liquid chromatography coupled to mass
      spectrometry/electron spray ionization (LC-MS/ESI) was used to characterize the
      polyphenolic profile of the OFIEOH extract. Fifteen compounds were identified in
      the OFIEOH extract, such as methyl, glycosylated and aglycone quercetin
      derivatives and aglycone and glycosylated kaempferol derivatives. Tri
      glycosylated methyl quercetin derivatives were the main compounds identified. In
      vitro egg hatch (EHT) and larval migration tests (LMT) were used in a range of
      concentrations of OFIEOH from 12.5 to 100 mg/mL for EHT and 12.5 to 200 mg/mL for
      LMT. In addition, the LMT was used to test ivermectin (IVM) (from 11.4 to 57.1
      uM), associated with the inhibitory concentration of 50% (IC50) for OFIEOH. The
      combination of OFIEOH (12.5 to 200 mg/mL) plus the IC50 of IVM was also tested.
      The efficacy of OFIEOH alone varied from 19.33 to 90.0% using the EHT. The LMT
      revealed an efficacy of 5.78 to 77.26% for the extract. Both tests showed a
      concentration-dependence inhibitory effect. We found a drug-extract antagonistic
      neutralizing effect when doses of IVM were added to OFIEOH (maximum efficacy of
      73.78%), while a positive additive effect was observed when OFIEOH was added to
      the IC50 of IVM (IC50 of 82.79 for OFIEOH alone against an IC50 of 55.08 of
      OFIEOH + IVM). The data from this work indicate that OFIEOH alone may be
      considered as a suitable ecofriendly product to control gastrointestinal
      parasites of sheep, offering a more holistic approach to improve animal farming
      and welfare. The drug-extract interaction is also a promising therapeutic
      alternative, reducing the final dose to the host, with an optimum combination
      effect.

PMID- 30213061
TI  - "On-Water" Synthesis of Quinazolinones and Dihydroquinazolinones Starting from o
      Bromobenzonitrile.
AB  - A versatile and practical "on-water" protocol was newly developed to synthesize
      quinazolinones using o-bromobenzonitrile as a novel starting material. Studies
      have found that air as well as water plays an important role in synthesis of
      quinazolinones. Further investigation indicated that dihydroquinazolinones can be
      prepared with this protocol under the protection of N2. The protocol can be
      extended to other substrates and various quinazolinones and dihydroquinazolinones
      were obtained. o-Bromobenzamide, o-aminobenzonitrile, and o-aminobenzamide were
      also evaluated as starting materials, and the results further proved the
      versatility of this protocol, especially towards dihydroquinazolinones.

PMID- 30213063
TI  - Carbon Black-Carbon Nanotube Co-Doped Polyimide Sensors for Simultaneous
      Determination of Ascorbic Acid, Uric Acid, and Dopamine.
AB  - Carbon black (CB) and carbon nanotube (CNT) co-doped polyimide (PI) modified
      glassy carbon electrode (CB-CNT/PI/GCE) was first prepared for the simultaneous
      determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA). The CB
      CNT/PI/GCE exhibited persistent electrochemical behavior and excellent catalytic
      activities. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were
      used for the simultaneous detection of AA, DA, and UA in their ternary mixture.
      The peak separations between AA and DA, and DA and UA, are up to 166 mV and 148
      mV, respectively. The CB-CNT/PI/GCE exhibited high sensitivity to DA and UA, with
      the detection limit of 1.9 uM and 3 uM, respectively. In addition, the CB
      CNT/PI/GCE showed sufficient selectivity and long-term stability, and was
      applicable to detect AA, DA, and UA in human urine sample.

PMID- 30213064
TI  - Influence of the Quartz Deformation Structures for the Occurrence of the Alkali
      Silica Reaction.
AB  - Defects in the crystalline structure of quartz facilitate the connection with the
      alkali hydroxides, since under a high alkalinity condition (e.g., in concrete),
      the Si-O bonds of quartz are easily broken. This study set out to investigate the
      influence of the deformation structures of quartz on its susceptibility to the
      alkali-silica reaction. A granite, a protomylonite, and a mylonite were selected
      for this study. Using optical microscopy, the quartz grains contained in these
      rocks were quantified and their texture characterized. The quartz samples
      extracted from the rocks were analyzed by magnetic nuclear resonance, to evaluate
      their potential for dissolving silica as well as changes in their atomic scale
      before and after the reaction with alkali hydroxides. These analyses were
      compared with the results of the accelerated mortar bar test. The study showed
      that the quartz with intense undulatory extinction and deformation bands denotes
      the most favorable condition to the development of the alkali-silica reaction.
      However, on an atomic scale, the slightly deformed grains were highly prone to
      react. Thus, in a high alkalinity condition, over a long period of time, any
      quartz tends to develop the alkali-silica reaction, regardless of the deformation
      degree of the grain.

PMID- 30213062
TI  - Wholegrain Intake and Risk of Type 2 Diabetes: Evidence from Epidemiological and
      Intervention Studies.
AB  - Type 2 diabetes mellitus (T2DM) is one of the most common metabolic diseases and
      represents a leading cause of morbidity and mortality because of its related
      complications. The alarming rise in T2DM prevalence worldwide poses enormous
      challenges in relation to its social, economic, and a clinical burden requiring
      appropriate preventive strategies. Currently, lifestyle modifications-including
      approaches to promote a moderate body weight reduction and to increase regular
      physical exercise-are the first crucial intervention for T2DM prevention. In the
      light of the difficulty in reducing body weight and in long-term maintenance of
      weight loss, quality changes in dietary patterns-in terms of macro and
      micronutrient composition-can also strongly affect the development of T2DM. This
      may provide a more practical and suitable preventative approach than simply
      implementing caloric restriction. Along this line, there is increasing evidence
      that wholegrain consumption in substitution of refined grains is associated with
      a reduction of the incidence of several non-communicable chronic diseases. The
      aim of the present review is to summarize the current evidence from observational
      and randomized controlled clinical trials on the benefits of wholegrain on T2DM
      prevention and treatment. Plausible mechanisms by which wholegrain could act on
      glucose homeostasis and T2DM prevention are also evaluated. Altogether, the
      totality of the available evidence supports present dietary recommendations
      promoting wholegrain foods for the prevention and treatment of T2DM.

PMID- 30213065
TI  - Mechanical and Sorptivity Characteristics of Edge-Oxidized Graphene Oxide (EOGO)
      Cement Composites: Dry- and Wet-Mix Design Methods.
AB  - This paper aims to investigate the effects of edge-oxidized graphene oxide
      nanoflakes (EOGO) on the mechanical properties and sorptivity of cement
      composites. The EOGO used in this study was produced by a mechanochemical process
      that assists the production of EOGO in large quantities at significantly reduced
      costs, enabling its practical use for infrastructure construction. The scope of
      this work includes the use of EOGO as an additive in cement composites, including
      cement paste and mortar. This study explores two mixing methods: The dry-mix
      method and the wet-mix method. The dry-mix method uses EOGO as dry powder in
      cement composites whereas the wet-mix method uses a water-dispersed solution
      (using a sonication process). Varied percentages of EOGO, ranging from 0.01% to
      1.0%, were used for both methods. To evaluate the concrete durability, the effect
      of EOGO addition on sorptivity of the cement composites was investigated by
      performing total porosity and water sorptivity tests. It was found that 0.05% of
      EOGO is the optimum proportion to exert the highest strength in compressive and
      flexural strength tests. In addition, the dry-mix method is comparable to the wet
      mix method (with dispersion of EOGO), thus more practical for field engineering
      applications.

PMID- 30213066
TI  - Competition among Supply Chains and Governmental Policy: Considering Consumers'
      Low-Carbon Preference.
AB  - Many manufacturers and retailers have cooperated for low-carbon production in
      various industries. This study examines the role of consumers' low-carbon
      preference in this cooperation. We construct four scenarios to investigate the
      effects of consumers' low-carbon preference on the market equilibrium of supply
      chains' product selection strategy. Based on the game theoretic models, optimal
      solutions for the two supply chains are derived with different consumers'
      preference for low-carbon products. Through the discussion, we uncovered the
      influence of consumers' preference on price and demand and the relationship
      between the influence coefficient of retailers' promotional effort on consumers'
      utility and retailer profits. In addition, given the increase of government's low
      carbon production subsidy, two supply chains will both more likely choose low
      carbon production. Interestingly, under the government subsidy, the profit of
      manufacturer will increase or decrease more than its retailer and the market
      structure will not change if the two supply chains have chosen low-carbon
      production.

PMID- 30213067
TI  - Folic Acid Has a Protective Effect on Retinal Vascular Endothelial Cells against
      High Glucose.
AB  - Diabetic retinopathy (DR) is a severe complication of diabetes, which seriously
      affects the life quality of patients. Because of the damage caused by DR, there
      is an urgent need to develop effective drugs. Folic acid, a water-soluble
      vitamin, is one of the vitamin B complexes. Folic acid is widely found in the
      meat and vegetables. In the clinic, low folic acid levels in the body may have a
      certain correlation with DR. However, there is no relevant basic research proving
      a relationship between folic acid levels and DR. The purpose of this study was
      therefore to investigate whether folic acid has a protective effect on the
      retinal vascular endothelial cells against high glucose levels. Moreover, the
      molecular mechanism of action of folic acid was further explored. The results
      showed that folic acid significantly suppressed the cell viability, tube length,
      migrated cells and the percentage of BrdU+ cells compared with the high glucose
      group. Moreover, folic acid decreased the mRNA expression of TEAD1 and the
      protein expression of TEAD1 and YAP1. These findings indicate that folic acid can
      protect retinal vascular endothelial cells from high glucose-induced injury by
      regulating the proteins in the Hippo signaling pathway.

PMID- 30213068
TI  - Air Pollution, Autophagy, and Skin Aging: Impact of Particulate Matter (PM10) on
      Human Dermal Fibroblasts.
AB  - A World Health Organization (WHO) report from 2016 states that over 3 million
      people die annually from air pollution, which places air pollution as the world's
      largest single environmental health risk factor. Particulate matter (PM) is one
      of the main components of air pollution, and there is increasing evidence that PM
      exposure exerts negative effects on the human skin. To see the impact of air
      pollution on skin aging, we analyzed the effect of PM exposure on human dermal
      fibroblasts (HDFs) with Western blot, enzyme-linked immunosorbent assay (ELISA),
      and gene analysis. Cultured HDFs were exposed to PM10 at a concentration of 30
      ug/cm2 for 24 h, and their gene/protein expression of inflammatory cytokines,
      fibroblast chemical mediators, and autophagy were assessed. A total of 1977 genes
      were found to be differentially expressed following PM exposure. We observed a
      significantly increased expression of pro-inflammatory genes interleukin (IL)
      1beta, IL-6, IL-8 and IL-33 in dermal fibroblasts exposed to PM10. Protein
      expression of IL-6 and IL-8 also significantly increased, which complemented our
      gene analysis results. In addition, there was a significant increase in
      cytochrome P450 (CYP1A1, CYP1B1), matrix metalloproteinase (MMP-1, MMP-3) mRNA
      expression, and significant decrease in transforming growth factor (TGF)-beta,
      collagen type I alpha chain (COL1A1, COL1A2), and elastin (ELN) mRNA expression
      in PM-exposed dermal fibroblasts. Protein expression of MMP-1 was significantly
      increased and that of TGF-beta and procollagen profoundly decreased, similar to
      the gene analysis results. Autophagy, an integrated cellular stress response, was
      also increased while transmission electron microscopy (TEM) analysis provided
      evidence of PM internalization in the autolysosomes. Taken together, our results
      demonstrate that PM10 contributes to skin inflammation and skin aging via
      impaired collagen synthesis. Increased autophagy in our study suggests a
      reparative role of autophagy in HDFs stressed with PM, but its biological
      significance requires further research.

PMID- 30213069
TI  - Regulatory Mechanism of ABA and ABI3 on Vegetative Development in the Moss
      Physcomitrella patens.
AB  - The moss Physcomitrella patens is a model system for studying plant developmental
      processes. ABSCISIC ACID INSENSITIVE3 (ABI3), a transcription factor of the ABA
      signaling pathway, plays an important role in plant growth and development in
      vascular plant. To understand the regulatory mechanism of ABA and PpABI3 on
      vegetative development in Physcomitrella patens, we applied physiological,
      cellular, and RNA-seq analyses in wild type (WT) plants and ?abi3 mutants. During
      ABA treatment, the growth of gametophytes was inhibited to a lesser extent ?abi3
      plants compared with WT plants. Microscopic observation indicated that the
      differentiation of caulonemata from chloronemata was accelerated in ?abi3 plants
      when compared with WT plants, with or without 10 MUM of ABA treatment. Under
      normal conditions, auxin concentration in ?abi3 plants was markedly higher than
      that in WT plants. The auxin induced later differentiation of caulonemata from
      chloronemata, and the phenotype of ?abi3 plants was similar to that of WT plants
      treated with exogenous indole-3-acetic acid (IAA). RNA-seq analysis showed that
      the PpABI3-regulated genes overlapped with genes regulated by the ABA treatment,
      and about 78% of auxin-related genes regulated by the ABA treatment overlapped
      with those regulated by PpABI3. These results suggested that ABA affected
      vegetative development partly through PpABI3 regulation in P. patens; PpABI3 is a
      negative regulator of vegetative development in P. patens, and the vegetative
      development regulation by ABA and PpABI3 might occur by regulating the expression
      of auxin-related genes. PpABI3 might be associated with cross-talk between ABA
      and auxin in P. patens.

PMID- 30213070
TI  - Transcriptomic Signature of Right Ventricular Failure in Experimental Pulmonary
      Arterial Hypertension: Deep Sequencing Demonstrates Mitochondrial, Fibrotic,
      Inflammatory and Angiogenic Abnormalities.
AB  - Right ventricular failure (RVF) remains the leading cause of death in pulmonary
      arterial hypertension (PAH). We investigated the transcriptomic signature of RVF
      in hemodynamically well-phenotyped monocrotaline (MCT)-treated, male, Sprague
      Dawley rats with severe PAH and decompensated RVF (increased right ventricular
      (RV) end diastolic volume (EDV), decreased cardiac output (CO), tricuspid annular
      plane systolic excursion (TAPSE) and ventricular-arterial decoupling). RNA
      sequencing revealed 2547 differentially regulated transcripts in MCT-RVF RVs.
      Multiple enriched gene ontology (GO) terms converged on mitochondria/metabolism,
      fibrosis, inflammation, and angiogenesis. The mitochondrial transcriptomic
      pathway is the most affected in RVF, with 413 dysregulated genes. Downregulated
      genes included TFAM (-0.45-fold), suggesting impaired mitochondrial biogenesis,
      CYP2E1 (-3.8-fold), a monooxygenase which when downregulated increases oxidative
      stress, dehydrogenase/reductase 7C (DHRS7C) (-2.8-fold), consistent with
      excessive autonomic activation, and polypeptide N-acetyl-galactose-aminyl
      transferase 13 (GALNT13), a known pulmonary hypertension (PH) biomarker (-2.7
      fold). The most up-regulated gene encodes Periostin (POSTN; 4.5-fold), a
      matricellular protein relevant to fibrosis. Other dysregulated genes relevant to
      fibrosis include latent-transforming growth factor beta-binding protein 2
      (LTBP2), thrombospondin4 (THBS4). We also identified one dysregulated gene
      relevant to all disordered transcriptomic pathways, ANNEXIN A1. This anti
      inflammatory, phospholipid-binding mediator, is a putative target for therapy in
      RVF-PAH. Comparison of expression profiles in the MCT-RV with published
      microarray data from the RV of pulmonary artery-banded mice and humans with bone
      morphogenetic protein receptor type 2 (BMPR2)-mutations PAH reveals substantial
      conservation of gene dysregulation, which may facilitate clinical translation of
      preclinical therapeutic and biomarkers studies. Transcriptomics reveals the
      molecular fingerprint of RVF to be heavily characterized by mitochondrial
      dysfunction, fibrosis and inflammation.

PMID- 30213072
TI  - Investigation of the Antioxidant Capacity, Insecticidal Ability and Oxidation
      Stability of Chenopodium formosanum Seed Extract.
AB  - To maximize the extraction of antioxidants from Chenopodium formosanum seeds, the
      process factors, such as the ethanol concentration (0-100%), extraction time (30
      180 min) and temperature (30-70  degrees C), for the extraction of the bioactive
      contents as well as the antioxidant capacity are evaluated using response surface
      methodology (RSM). The experimental results fit well with quadratic models. The
      extract was identified by GC/MS, and it was found that some active compounds had
      antioxidant, repellency and insecticidal activities. Various concentrations of
      the extract were prepared for the evaluation of the insecticidal activity against
      Tribolium castaneum, and the toxicity test results indicated that the extract was
      toxic to Tribolium castaneum, with an LC50 value of 354.61 ppm. The oxidative
      stability of the olive oil determined according to the radical scavenging
      activity and p-anisidine test demonstrates that the extract obtained from the
      Chenopodium formosanum seeds can retard lipid oxidation.

PMID- 30213071
TI  - Prevalence of Depression among Migrants: A Systematic Review and Meta-Analysis.
AB  - As the number of migrants worldwide increases, it is worthwhile to examine the
      extent to which depression has affected this group of often vulnerable
      individuals. The purpose of this systematic review and meta-analysis is to
      examine the aggregate prevalence of depression among international migrants and
      to explore the variations in prevalence with demographic and educational factors.
      A search was conducted on the online databases PubMed and ScienceDirect whole
      using the terms "depression", "depressive disorder", "immigration", "immigrant",
      "migration", and "migrant". A total of 25 studies met our inclusion criteria. A
      random-effects model meta-analysis calculated an aggregate prevalence of 15.6%
      among migrants. Heterogeneity was identified by meta-regression and subgroup
      analyses, and the level of educational attainment, employment status, and length
      of residency spent in country of migration were found to be significant
      moderators contributing to depression prevalence. In conclusion, newly arrived
      migrants appear to be susceptible to developing depression and it is imperative
      that more in the form of preventive strategies and increased assistance be
      incorporated to ensure their psychological wellbeing and improve their mental
      health outcomes. Further research should be conducted to better understand the
      risk of psychiatric disorders among members of this subpopulation.

PMID- 30213074
TI  - Synthesis and Irreversible Thermochromic Sensor Applications of Manganese Violet.
AB  - An irreversible thermochromic material based on manganese violet (MnNH4P2O7) is
      synthesized. The crystal phase, chemical composition, and morphology of the
      synthesized material are analyzed using X-ray diffraction, scanning electron
      microscopy coupled with energy-dispersive X-ray spectrometry, and Fourier
      transform infrared spectroscopy. The absorption spectra of the synthesized
      material are obtained using a UV-Vis spectrometer, and the thermochromism
      exhibited by the powdered samples at high temperatures is also investigated. The
      as-synthesized manganese violet pigment consists of pure alpha-MnNH4P2O7 phase.
      In addition, the synthesized pigment largely consists of hexagonal crystals with
      a diameter of hundreds of nanometers. On heating, the pigment simultaneously
      loses H2O and NH3 in two successive steps at approximately 330-434.4  degrees C
      and 434.4-527  degrees C, which correspond to the formation of an intermediate
      phase and of Mn2P4O12, respectively. An overall mass loss of 14.22% is observed,
      which is consistent with the expected 13.79%. An irreversible color change from
      violet to white is observed after exposure of the synthesized manganese violet
      pigment at 400  degrees C for 30 min. This is attributed to the oxidation of
      ammonia to hydroxylamine, which then decomposes to nitrogen and water, or
      alternatively to the direct oxidation of ammonia to nitrogen. Furthermore, we
      demonstrate the potential application of synthesized manganese violet in the
      production of irreversible thermochromic paint by mixing with potassium silicate
      solution as a binder and deionized water as a solvent at a specific ratio. The
      thermochromic paint is then applied in fabrication of irreversible thermochromic
      sensors by coating it onto a steel plate surface. Finally, we show that manganese
      violet-based irreversible thermochromic sensors are able to detect temperatures
      around 400  degrees C by changing color from violet to white/milky.

PMID- 30213073
TI  - Resveratrol Suppresses Matrix Metalloproteinase-2 Activation Induced by
      Lipopolysaccharide in Mouse Osteoblasts via Interactions with AMP-Activated
      Protein Kinase and Suppressor of Cytokine Signaling 1.
AB  - Porphyromonas endodontalis (P. endodontalis) lipopolysaccharide (LPS) is
      associated with the progression of bone resorption in periodontal and periapical
      diseases. Matrix metalloproteinase-2 (MMP-2) expression and activity are elevated
      in apical periodontitis and have been suggested to participate in bone
      resorption. Therefore, inhibiting MMP-2 activation may be considered a
      therapeutic strategy for treating apical periodontitis. Resveratrol is a natural
      non-flavonoid polyphenol that has been reported to have antioxidant, anti-cancer,
      and anti-inflammatory properties. However, the capacity of resveratrol to protect
      osteoblast cells from P. endodontalis LPS insults and the mechanism of its
      inhibitory effects on MMP-2 activation is poorly understood. Here, we demonstrate
      that cell viability is unchanged when 10 mg L-1P. endodontalis LPS is used, and
      MMP-2 expression is drastically induced by P. endodontalis LPS in a concentration
      and time-dependent manner. Twenty micromolar resveratrol did not reduce MC3T3-E1
      cell viability. Resveratrol increased AMP-activated protein kinase (AMPK)
      phosphorylation, and Compound C, a specific AMPK inhibitor, partially abolished
      the resveratrol-mediated phosphorylation of AMPK. In addition, AMPK inhibition
      blocked the effects of resveratrol on MMP-2 expression and activity in LPS
      induced MC3T3-E1 cells. Treatment with resveratrol also induced suppressor of
      cytokine signaling 1 (SOCS1) expression in MC3T3-E1 cells. SOCS1 siRNA negated
      the inhibitory effects of resveratrol on LPS-induced MMP-2 production.
      Additionally, resveratrol-induced SOCS1 upregulation was reduced by treatment
      with compound C. These results demonstrate that AMPK and SOCS1 activation are
      important signaling events during resveratrol-mediated inhibition of MMP-2
      production in response to LPS in MC3T3-E1 cells, and there is crosstalk between
      AMPK and SOCS1 signaling.

PMID- 30213075
TI  - G9a Correlates with VLA-4 Integrin and Influences the Migration of Childhood
      Acute Lymphoblastic Leukemia Cells.
AB  - Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. As ALL
      progresses, leukemic cells cross the endothelial barrier and infiltrate other
      tissues. Epigenetic enzymes represent novel therapeutic targets in hematological
      malignancies, and might contribute to cells' capacity to migrate across physical
      barriers. Although many molecules drive this process, the role of the nucleus and
      its components remain unclear. We report here, for the first time, that the
      expression of G9a (a histone methyltransferase related with gene silencing)
      correlates with the expression of the integrin subunit alpha4 in children with
      ALL. We have demonstrated that G9a depletion or its inhibition with BIX01294
      abrogated the ability of ALL cells to migrate through an endothelial monolayer.
      Moreover, G9a-depleted and BIX01294-treated cells presented bigger nuclei and
      more adherent phenotype than control cells on endothelial monolayers. Blocking
      G9a did not affect the cell cytoskeleton or integrin expression of ALL cell
      lines, and only its depletion reduced slightly F-actin polymerization. Similarly
      to the transendothelial migration, G9a inhibition impaired the cell migration
      induced by the integrin VLA-4 (alpha4beta1) of primary cells and ALL cell lines
      through narrow spaces in vitro. Our results suggest a cellular connection between
      G9a and VLA-4, which underlies novel functions of G9a during ALL cell migration.

PMID- 30213076
TI  - Stress-Driven Discovery of New Angucycline-Type Antibiotics from a Marine
      Streptomyces pratensis NA-ZhouS1.
AB  - Natural products from marine actinomycetes remain an important resource for drug
      discovery, many of which are produced by the genus, Streptomyces. However, in
      standard laboratory conditions, specific gene clusters in microbes have long been
      considered silent or covert. Thus, various stress techniques activated latent
      gene clusters leading to isolation of potential metabolites. This study focused
      on the analysis of two new angucycline antibiotics isolated from the culture
      filtrate of a marine Streptomyces pratensis strain NA-ZhouS1, named, stremycin A
      (1) and B (2) which were further determined based on spectroscopic techniques
      such as high resolution time of flight mass spectrometry (HR-TOF-MS), 1D, and 2D
      nuclear magnetic resonance (NMR) experiments. In addition, four other known
      compounds, namely, 2-[2-(3,5-dimethyl-2-oxo-cyclohexyl)-6-oxo-tetrahydro-pyran
      4yl]-acetamide (3), cyclo[l-(4-hydroxyprolinyl)-l-leucine] (4), 2-methyl-3H
      quinazoline-4-one (5), and menthane derivative, 3-(hydroxymethyl)-6-isopropyl
      10,12-dioxatricyclo[7.2.1.0]dodec-4-en-8-one (6) were obtained and elucidated by
      means of 1D NMR spectrometry. Herein, we describe the "Metal Stress Technique"
      applied in the discovery of angucyclines, a distinctive class of antibiotics that
      are commonly encoded in microbiomes but have never been reported in "Metal
      Stress" based discovery efforts. Novel antibiotics 1 and 2 exhibited
      antimicrobial activities against Pseudomonas aeruginosa, methicillin resistant
      Staphylococcus aureus (MRSA), Klebsiella pneumonia, and Escherichia coli with
      equal minimum inhibitory concentration (MIC) values of 16 ug/mL, while these
      antibiotics showed inhibition against Bacillus subtilis at MIC value of
      approximately 8-16 ug/mL, respectively. As a result, the outcome of this
      investigation revealed that metal stress is an effective technique in unlocking
      the biosynthetic potential and resulting production of novel antibiotics.

PMID- 30213078
TI  - Benefits of Multi-Constellation/Multi-Frequency GNSS in a Tightly Coupled
      GNSS/IMU/Odometry Integration Algorithm.
AB  - Localization algorithms based on global navigation satellite systems (GNSS) play
      an important role in automotive positioning. Due to the advent of autonomously
      driving cars, their importance is expected to grow even further in the next
      years. Simultaneously, the performance requirements for these localization
      algorithms will increase because they are no longer used exclusively for
      navigation, but also for control of the vehicle's movement. These requirements
      cannot be met with GNSS alone. Instead, algorithms for sensor data fusion are
      needed. While the combination of GNSS receivers with inertial measurements units
      (IMUs) is a common approach, it is traditionally executed in a single
      frequency/single-constellation architecture, usually with the Global Positioning
      System's (GPS) L1 C/A signal. With the advent of new GNSS constellations and
      civil signals on multiple frequencies, GNSS/IMU integration algorithm performance
      can be improved by utilizing these new data sources. To achieve this, we upgraded
      a tightly coupled GNSS/IMU integration algorithm to process measurements from GPS
      (L1 C/A, L2C, L5) and Galileo (E1, E5a, E5b). After investigating various
      combination strategies, we chose to preferably work with ionosphere-free
      combinations of L5-L1 C/A and E5a-E1 pseudo-ranges. L2C-L1 C/A and E5b-E1
      combinations as well as single-frequency pseudo-ranges on L1 and E1 serve as
      backup when no L5/E5a measurements are available. To be able to process these six
      types of pseudo-range observations simultaneously, the differential code biases
      (DCBs) of the employed receiver need to be calibrated. Time-differenced carrier
      phase measurements on L1 and E1 provide the algorithm with pseudo-range-rate
      observations. To provide additional aiding, information about the vehicle's
      velocity obtained by an odometry model fed with angular velocities from all four
      wheels as well as the steering wheel angle is incorporated into the algorithm. To
      evaluate the performance improvement provided by these new data sources, two sets
      of measurement data are collected and the resulting navigation solutions are
      compared to a higher-grade reference system, consisting of a geodetic GNSS
      receiver for real-time kinematic positioning (RTK) and a navigation grade IMU.
      The multi-frequency/multi-constellation algorithm with odometry aiding achieves a
      3-D root mean square (RMS) position error of 3.6 m / 2.1 m in these data sets,
      compared to 5.2 m / 2.9 m for the single-frequency GPS algorithm without odometry
      aiding. Odometry is most beneficial to positioning accuracy when GNSS measurement
      quality is poor. This is demonstrated in data set 1, resulting in a reduction of
      the horizontal position error's 95% quantile from 6.2 m without odometry aiding
      to 4.2 m with odometry aiding.

PMID- 30213077
TI  - The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive
      Phytochemicals Targeting the TLR4 Signaling Pathway.
AB  - Toll-like receptors (TLRs) are a well-known family of pattern recognition
      receptors that play an important role in a host immune system. TLR triggering
      leads to the induction of pro-inflammatory cytokines and chemokines, driving the
      activation of both innate and adaptive immunity. Recently, an increasing number
      studies have shown the link between TLRs and cancer. Among them, the toll-like
      receptor 4 (TLR4) signaling pathway is associated with inflammatory response and
      cancer progression. Dietary phytochemicals are potential modulators of
      immunological status with various pharmacological properties including anti
      cancer, anti-oxidant and anti-inflammatory. Curcumin, 6-gingerol, 6-shogaol, 1
      dehydro-10-gingerdione, epigallocatechin gallate (EGCG), luteolin, quercetin,
      resveratrol, caffeic acid phenethyl ester, xanthohumol, genistein, berberine, and
      sulforaphane can inhibit TLR4 activation. The aim of the present review is to
      describe the role of the TLR4 signaling pathway between inflammatory response and
      cancer progression. We further introduce bioactive phytochemicals with potential
      anti-inflammation and chemoprevention by inhibiting TLR activation.

PMID- 30213079
TI  - Multidisciplinary Perioperative Care for Children with Neuromuscular Disorders.
AB  - Children with neuromuscular diseases present unique challenges to providing safe
      and appropriate perioperative care. Given the spectrum of disease etiologies and
      manifestations, this is a population that often requires specialized
      multidisciplinary care from pediatricians, geneticists, neurologists, dieticians,
      and pulmonologists which must also be coordinated with surgeons and
      anesthesiologists when these patients present for surgery. Several of these
      diseases also have specific pharmacologic implications for anesthesia, most
      notably mitochondrial disease and muscular dystrophies, which put them at
      additional risk during the perioperative period particularly in patients
      presenting without a formal diagnosis. Techniques and strategies to fully
      evaluate and optimize these patients preoperatively, manage them safely
      intraoperatively, and return them to their baseline status postoperative are
      particularly important in this vulnerable group of patients. Utilizing a review
      of inherited neuromuscular conditions, generalized perioperative concerns, and
      specific complications related to anesthesia, this article provides an overview
      of pertinent considerations and recommends a framework for management of these
      patients.

PMID- 30213080
TI  - Excessive Weight Gain Followed by Catch-Down in Exclusively Breastfed Infants: An
      Exploratory Study.
AB  - Some infants experience excessive weight gain (EWG) during exclusive
      breastfeeding, but causes and consequences are unknown. The objective was to
      identify factors associated with early EWG. Infants with EWG (HW-group) were
      examined at 5, 9 and 18 mo and compared to a breastfed group with normal weight
      gain (NW-group). Anthropometry, body composition, milk and blood samples, and
      milk intake were measured. Mean body-mass-index-for-age z-scores (BAZ) increased
      1.93 from birth to 5 mo in the HW-group (n = 13) while the NW-group (n = 17) was
      unchanged (-0.01). The HW-group had 70% more fat mass at 5 mo, and then showed
      marked catch-down in BAZ from 5 to 18 mo (-0.84). Milk intake at 5-6 mo did not
      differ between the groups. In the HW-group milk-leptin was lower at 5 mo and
      serum-leptin was considerably higher at 5 and 9 mo compared to the NW-group.
      Serum-leptin at 5 mo was positively associated with weight-for-age z-score (WAZ)
      and fat mass and negatively with WAZ change from 5 to 9 mo. In conclusion,
      breastfed infants with EWG had catch-down growth when other foods were
      introduced. Low milk-leptin in the HW-group may have stimulated appetite and milk
      intake when weight gain was high. High serum-leptin in the HW-group suggests
      early leptin resistance, which could impact cerebral regulation of energy intake.
      Larger studies are needed to confirm these results.

PMID- 30213081
TI  - Magnetic Noise Prediction and Evaluation in Tunneling Magnetoresistance Sensors.
AB  - We propose a simple model for prediction of magnetic noise level in tunneling
      magnetoresistance (TMR) sensors. The model reproduces experimental magnetic 1/f
      and white noise components, which are dependent on sensors resistance and field
      sensitivity. The exact character of this dependence is determined by comparing
      the results with experimental data using a statistical cross-validation
      procedure. We show that the model is able to correctly predict magnetic noise
      level for systems within wide range of resistance, volume and sensitivity, and
      that it can be used as a robust method for noise evaluation in TMR sensors based
      on a small number of easily measurable parameters only.

PMID- 30213084
TI  - Supervised PolSAR Image Classification with Multiple Features and Locally Linear
      Embedding.
AB  - In this paper, we propose a new method of land use and land cover classification
      for polarimetric SAR data. This algorithm consists of three parts. First, the
      multiple-component model-based scattering decomposition technique is improved and
      the decomposed scattering powers can be used to support the classification of
      PolSAR data. With this decomposition, the volume scattering of vegetated areas is
      enhanced while their double-bounce scattering is reduced. Furthermore, the double
      bounce scattering of urban areas is enhanced and their volume scattering is
      decreased, which leads to an improvement in the classification accuracy
      especially for the urban areas. Second, this classification strategy is carried
      out on the superpixel level, which can decrease the influence of speckle noise
      and speed up the classification. Moreover, the contexture and spatial features
      extracted from these superpixels are utilized to improve classification accuracy.
      Lastly, we introduce the supervised locally linear embedding approach to map the
      high dimensional features into the low dimensional features as the inputs of
      classifiers. The classification is completed using the nearest neighbor
      classifier. The effectiveness of our proposed method is demonstrated using the
      AIRSAR C-band PolSAR data set, which is compared with the original MCSM-SVM and
      newly published LE-IF PolSAR classification methods. Further investigation is
      also carried out on the individual contribution of the three parts to LULC
      classification using AIRSAR C-band data. It indicates that all three components
      have important contributions to the final classification result.

PMID- 30213083
TI  - Hydrogen Peroxide Diffusion through Enamel and Dentin.
AB  - The purpose of this study was to evaluate the in vitro diffusion of commercial
      bleaching products (hydrogen peroxide (HP) or carbamide peroxide (CP) based) with
      different application protocols. Human enamel-dentin discs were obtained and
      divided into 20 groups. Four commercial products based on HP (Pola Office+(PO),
      Perfect Bleach (PB), Norblanc Office-automix (NO), and Boost (BT)), and one based
      on CP (PolaDay CP (PD)), were evaluated with different application protocols (3
      applications * 10 min or 1 application * 30 min, with or without light
      activation). Artificial pulp chambers with 100 uL of a buffer solution were
      prepared. After each application, the buffer was removed and diffused HP was
      quantified by fluorimetry. Data were analyzed with two-way analysis of variance
      (ANOVA) and Tukey's test. In groups where 3 * 10 min applications were done,
      after the first 10 min, PB, NO, and PD showed similar diffusion (p < 0.05). After
      the second and third applications, diffusion proved similar for PO and PD, while
      PB exhibited the greatest diffusion. In the 30 min application groups, PO and BT
      showed no significant differences (p > 0.05), with similar results for NO and PD.
      Comparing products with or without light activation, PO, BT, and PB showed
      significantly greater diffusion with light activation (p < 0.05). Reapplication,
      and light activation, increased HP diffusion independently of the concentration
      of the product.

PMID- 30213082
TI  - Omega-3 Fatty Acids Prevent Early Pancreatic Carcinogenesis via Repression of the
      AKT Pathway.
AB  - Pancreatic cancer remains a daunting foe despite a vast number of accumulating
      molecular analyses regarding the mutation and expression status of a variety of
      genes. Indeed, most pancreatic cancer cases uniformly present with a mutation in
      the KRAS allele leading to enhanced RAS activation. Yet our understanding of the
      many epigenetic/environmental factors contributing to disease incidence and
      progression is waning. Epidemiologic data suggest that diet may be a key factor
      in pancreatic cancer development and potentially a means of chemoprevention at
      earlier stages. While diets high in omega3 fatty acids are typically associated
      with tumor suppression, diets high in omega6 fatty acids have been linked to
      increased tumor development. Thus, to better understand the contribution of these
      polyunsaturated fatty acids to pancreatic carcinogenesis, we modeled early stage
      disease by targeting mutant KRAS to the exocrine pancreas and administered diets
      rich in these fatty acids to assess tumor formation and altered cell-signaling
      pathways. We discovered that, consistent with previous reports, the omega3
      enriched diet led to reduced lesion penetrance via repression of proliferation
      associated with reduced phosphorylated AKT (pAKT), whereas the omega6-enriched
      diet accelerated tumor formation. These data provide a plausible mechanism
      underlying previously observed effects of fatty acids and suggest that
      administration of omega3 fatty acids can reduce the pro-survival, pro-growth
      functions of pAKT. Indeed, counseling subjects at risk to increase their intake
      of foods containing higher amounts of omega3 fatty acids could aid in the
      prevention of pancreatic cancer.

PMID- 30213085
TI  - An Ontology-Based Cybersecurity Framework for the Internet of Things.
AB  - The use of sensors and actuators as a form of controlling cyber-physical systems
      in resource networks has been integrated and referred to as the Internet of
      Things (IoT). However, the connectivity of many stand-alone IoT systems through
      the Internet introduces numerous cybersecurity challenges as sensitive
      information is prone to be exposed to malicious users. This paper focuses on the
      improvement of IoT cybersecurity from an ontological analysis, proposing
      appropriate security services adapted to the threats. The authors propose an
      ontology-based cybersecurity framework using knowledge reasoning for IoT,
      composed of two approaches: (1) design time, which provides a dynamic method to
      build security services through the application of a model-driven methodology
      considering the existing enterprise processes; and (2) run time, which involves
      monitoring the IoT environment, classifying threats and vulnerabilities, and
      actuating in the environment ensuring the correct adaptation of the existing
      services. Two validation approaches demonstrate the feasibility of our concept.
      This entails an ontology assessment and a case study with an industrial
      implementation.

PMID- 30213086
TI  - Symmetry-Induced Structuring of Ultrathin FeO and Fe3O4 Films on Pt(111) and
      Ru(0001).
AB  - Iron oxide films epitaxially grown on close-packed metal single crystal
      substrates exhibit nearly-perfect structural order, high catalytic activity (FeO)
      and room-temperature magnetism (Fe3O4). However, the morphology of the films,
      especially in the ultrathin regime, can be significantly influenced by the
      crystalline structure of the used support. This work reports an ultra-high vacuum
      (UHV) low energy electron/synchrotron light-based X-ray photoemission electron
      microscopy (LEEM/XPEEM) and electron diffraction (uLEED) study of the growth of
      FeO and Fe3O4 on two closed-packed metal single crystal surfaces: Pt(111) and
      Ru(0001). The results reveal the influence of the mutual orientation of adjacent
      substrate terraces on the morphology of iron oxide films epitaxially grown on top
      of them. On fcc Pt(111), which has the same mutual orientation of adjacent
      monoatomic terraces, FeO(111) grows with the same in-plane orientation on all
      substrate terraces. For Fe3O4(111), one or two orientations are observed
      depending on the growth conditions. On hcp Ru(0001), the adjacent terraces of
      which are 'rotated' by 180 degrees  with respect to each other, the in-plane
      orientation of initial FeO(111) and Fe3O4(111) crystallites is determined by the
      orientation of the substrate terrace on which they nucleated. The adaptation of
      three-fold symmetric iron oxides to three-fold symmetric substrate terraces leads
      to natural structuring of iron oxide films, i.e., the formation of patch-like
      magnetite layers on Pt(111) and stripe-like FeO and Fe3O4 structures on Ru(0001).

PMID- 30213087
TI  - Green Preparation of Straw Fiber Reinforced Hydrolyzed Soy Protein
      Isolate/Urea/Formaldehyde Composites for Biocomposite Flower Pots Application.
AB  - The effects of soil burial on the biodegradation of biocomposite flower pots
      (BFP) made from straw fiber (SF) and hydrolyzed soy protein
      isolate/urea/formaldehyde (HSPI/U/F) copolymer resin were studied in detail. The
      microstructure, crystallinity, functional groups, mechanical, degradation and
      thermal property of the prepared SF with HSPI/U/F copolymer resin have been
      studied, and the degradation mechanism was also elucidated. XRD results showed
      that the bond breakage between SF and HSPI/U/F copolymer resin induced a decrease
      in relative degradation-resistant crystal structures. FTIR spectra showed that
      the methylolated HSPI units could form a cross-linking network with U/F and SF.
      The BFP degradation after soil burial was mainly attributed to the effects of
      microorganisms. The degradation products were environmentally friendly, because
      they were degradable and could fertilize the soil. In addition, the U/F adhesives
      were slightly degraded by the microorganisms due to the HSPI in the pots. The TG
      and DSC results showed that the molecular motion of the BFP matrix could be
      restricted by the degradation action and the content of HSPI, resulting in
      decreased crystallization enthalpy and showing good thermal property. The tensile
      strength of different reinforced samples was not significantly reduced in
      comparison to U/F resin, and still kept good mechanical performance. Thus, the
      prepared SF reinforced HSPI/U/F copolymer resins could have good potential for
      use in the field of biodegradable flower pots because of their good thermal
      property, mechanical property, biodegradability, and relatively low cost.

PMID- 30213088
TI  - Energy-Based Approach to Predict Fatigue Life of Asphalt Mixture Using Three
      Point Bending Fatigue Test.
AB  - The three-point bending fatigue tests were carried out in order to accurately
      predict the fatigue life of an asphalt mixture based on the plateau value (PV) of
      the dissipated strain energy ratio (DSER). The relations of the dissipated strain
      energy (DSE) to the stress-strength ratio, temperature and loading rate were
      studied, and the constructions of the mathematical models of DSE and DSER were
      completed based on the change laws of the DSE. The relation of the fatigue life
      to the PV was determined based on the analysis of damage evolution, based on
      which the fatigue equation was established and used to predict the fatigue life.
      The results show that the change laws of DSE and DSER can be well described by
      the proposed mathematical models. The PV is defined as the average value of the
      DSER in the second stage and the fatigue life decreases in power function with
      the increase of PV, based on which the fatigue equation of Nf = A(PV)B was
      established, and the established fatigue equation is very close to that is used
      in the MEPDG. The fatigue equation can well predict the fatigue life asphalt
      mixture.

PMID- 30213090
TI  - Determination of Eudragit(r) L100 in an Enteric-Coated Tablet Formulation Using
      Size-Exclusion Chromatography with Charged-Aerosol Detection.
AB  - Eudragit(r) L100 is a commonly used polymer in a coating layer of modified
      release drug formulation to prevent drug release in the stomach. The amount of
      Eudragit(r) L100 in the formula determines the dissolution profile of drug at its
      release medium. Hence, its quantification in reference product will facilitate
      the formulation of a bioequivalent drug product. Some analytical methods
      including size-exclusion chromatography (SEC) have been reported for
      characterization of Eudragit(r) L100 either as single component or its conjugate
      with the enzyme, but none for its quantification in drug formulation. In this
      work, an SEC method with charged-aerosol detection (CAD) was developed for
      determination of Eudragit(r) L100 in an enteric-coated tablet formulation using
      Waters Ultrahydrogel 1000 and Waters Ultrahydrogel 120 columns in series. The
      mobile phase was a mixture of 90:10 (v/v) 44.75 mM aqueous ammonium acetate
      buffer, pH 6.6 and acetonitrile pumped at a constant flow rate of 0.8 mL/min in
      isocratic mode. The method was validated for specificity, working range, limit of
      detection (LOD), limit of quantification (LOQ), accuracy and precision. The
      method was shown to be specific for Eudragit(r) L100 against the diluent (mobile
      phase) and placebo of a coating layer for the tablet. A good correlation
      coefficient (r = 0.9997) of CAD response against Eudragit(r) L100 concentration
      from 0.1-1.0 mg/mL was obtained using polynomial regression. LOD and LOQ
      concentrations were 0.0015 and 0.0040 mg/mL, respectively. The mean recovery of
      Eudragit(r) L100 was in the range of 88.0-91.1% at three levels of working
      concentration: 50%, 100% and 150%. Six replicated preparations of samples showed
      good precision of the peak area with % relative standard deviation (RSD) 2.7. In
      conclusion, the method was suitable for quantification of Eudragit(r) L100 in an
      enteric-coated tablet formulation.

PMID- 30213092
TI  - Comparing Interviewer-Administered and Web-Based Food Frequency Questionnaires to
      Predict Energy Requirements in Adults.
AB  - Traditional food frequency questionnaires (FFQs) are influenced by systematic
      error, but web-based FFQ (WEB-FFQs) may mitigate this source of error. The
      objective of this study was to compare the accuracy of interview-based and web
      based FFQs to assess energy requirements (mERs). The mER was measured in a series
      of controlled feeding trials in which participants daily received all foods and
      caloric drinks to maintain stable body weight over 4 to 6 weeks. FFQs assessing
      dietary intakes and hence mean energy intake were either interviewer-administered
      by a registered dietitian (IA-FFQ, n = 127; control method) or self-administered
      using a web-based platform (WEB-FFQ, n = 200; test method), on a single occasion.
      Comparison between self-reported energy intake and mER revealed significant under
      reporting with the IA-FFQ (-9.5%; 95% CI, -12.7 to -6.1) and with the WEB-FFQ (
      11.0%; 95% CI, -15.4 to -6.4), but to a similar extent between FFQs (p = 0.62).
      However, a greater proportion of individuals were considered as accurate
      reporters of energy intake using the IA-FFQ compared with the WEB-FFQ (67.7% vs.
      48.0%, respectively), while the prevalence of over-reporting was lower with the
      IA-FFQ than with the WEB-FFQ (6.3% vs. 17.5%, respectively). These results
      suggest less accurate prediction of true energy intake by a self-administered WEB
      FFQ than with an IA-FFQ.

PMID- 30213089
TI  - Microfluidic and Paper-Based Devices for Disease Detection and Diagnostic
      Research.
AB  - Recent developments in microfluidic devices, nanoparticle chemistry, fluorescent
      microscopy, and biochemical techniques such as genetic identification and
      antibody capture have provided easier and more sensitive platforms for detecting
      and diagnosing diseases as well as providing new fundamental insight into disease
      progression. These advancements have led to the development of new technology and
      assays capable of easy and early detection of pathogenicity as well as the
      enhancement of the drug discovery and development pipeline. While some studies
      have focused on treatment, many of these technologies have found initial success
      in laboratories as a precursor for clinical applications. This review highlights
      the current and future progress of microfluidic techniques geared toward the
      timely and inexpensive diagnosis of disease including technologies aimed at high
      throughput single cell analysis for drug development. It also summarizes novel
      microfluidic approaches to characterize fundamental cellular behavior and
      heterogeneity.

PMID- 30213091
TI  - Autoalgometry: An Important Tool for Pressure Pain Threshold Evaluation.
AB  - The term "pain threshold" refers to the measurement of the intensity of a
      physical stimulus that evokes pain. To estimate the pain threshold, a mechanical
      or electrical stimulus with increasing intensity is usually applied until the
      subject under evaluation refers to a pain sensation. This study aims to evaluate
      the autoalgometric pain threshold as a perfect technique to determine the effects
      of stimulation rate in relation to both gender and the site of stimulation. In
      this experimental model, pressure algometry was applied: the subject under
      evaluation pushed a finger against a small round metal tip, producing and at the
      same time controlling the intensity of the noxious stimulus. Through
      autoalgometry, the stimulus intensity was recorded over time, measuring the force
      change rate applied and studying the subject's behavior on approaching pain. This
      test was performed with 50 healthy volunteers on two days, applying a fast or
      slow rate of stimulation. The results described demonstrate that there is a
      positive correlation between the pressure increase rate and the pressure
      threshold evaluation. In light of these findings, autoalgometry can be proposed
      as an objective measure of pressure pain threshold for clinical and research use.

PMID- 30213093
TI  - Quantile Coarsening Analysis of High-Volume Wearable Activity Data in a
      Longitudinal Observational Study.
AB  - Owing to advances in sensor technologies on wearable devices, it is feasible to
      measure physical activity of an individual continuously over a long period. These
      devices afford opportunities to understand individual behaviors, which may then
      provide a basis for tailored behavior interventions. The large volume of data
      however poses challenges in data management and analysis. We propose a novel
      quantile coarsening analysis (QCA) of daily physical activity data, with a goal
      to reduce the volume of data while preserving key information. We applied QCA to
      a longitudinal study of 79 healthy participants whose step counts were monitored
      for up to 1 year by a Fitbit device, performed cluster analysis of daily
      activity, and identified individual activity signature or pattern in terms of the
      clusters identified. Using 21,393 time series of daily physical activity, we
      identified eight clusters. Employment and partner status were each associated
      with 5 of the 8 clusters. Using less than 2% of the original data, QCA provides
      accurate approximation of the mean physical activity, forms meaningful activity
      patterns associated with individual characteristics, and is a versatile tool for
      dimension reduction of densely sampled data.

PMID- 30213094
TI  - Geographical Accessibility of Community Health Assist System General
      Practitioners for the Elderly Population in Singapore: A Case Study on the
      Elderly Living in Housing Development Board Flats.
AB  - Accessible primary healthcare is important to national healthcare in general and
      for older persons in particular, in societies where the population is ageing
      rapidly, as in Singapore. However, although much policy and research efforts have
      been put into this area, we hardly find any spatial perspective to assess the
      accessibility of these primary healthcare services. This paper analyzes the
      geographical accessibility of one major healthcare service in Singapore, namely,
      General Practitioners (GPs) services under the Community Health Assist Scheme
      (CHAS) for older persons. A Python script was developed to filter the website
      data of the Housing Development Board (HDB) of Singapore. The data derived was
      comprehensively analyzed by an Enhanced 2-Step Floating Catchment Area (E2SFCA)
      method based on a Gaussian distance-decay function and the GIS technique. This
      enabled the identification of areas with relatively weak geographical
      accessibility of CHAS-GPs. The findings are discussed along with suggestions for
      health practitioners, service planners and policy makers. Despite its initial
      nature, this study has demonstrated the value of innovative approaches in data
      collection and processing for the elderly-related studies, and contributed to the
      field of healthcare services optimization and possibly to other human services.

PMID- 30213096
TI  - Bayesian Finite Element Model Updating and Assessment of Cable-Stayed Bridges
      Using Wireless Sensor Data.
AB  - We focus on a Bayesian inference framework for finite element (FE) model updating
      of a long-span cable-stayed bridge using long-term monitoring data collected from
      a wireless sensor network (WSN). A robust Bayesian inference method is proposed
      which marginalizes the prediction-error precisions and applies Transitional
      Markov Chain Monte Carlo (TMCMC) algorithm. The proposed marginalizing error
      precision is compared with other two treatments of prediction-error precisions,
      including the constant error precisions and updating error precisions through
      theoretical analysis and numerical investigation based on a bridge FE model.
      TMCMC is employed to draw samples from the posterior probability density function
      (PDF) of the structural model parameters and the uncertain prediction-error
      precision parameters if required. It is found that the proposed Bayesian
      inference method with prediction-error precisions marginalized as "nuisance"
      parameters produces an FE model with more accurate posterior uncertainty
      quantification and robust modal property prediction. When applying the identified
      modal parameters from acceleration data collected during a one-year period from
      the large-scale WSN on the bridge, we choose two candidate model classes using
      different parameter grouping based on the clustering results from a sensitivity
      analysis and apply Bayes' Theorem at the model class level. By implementing the
      TMCMC sampler, both the posterior distributions of the structural model
      parameters and the plausibility of the two model classes are characterized given
      the real data. Computation of the posterior probabilities over the candidate
      model classes provides a procedure for Bayesian model class assessment, where the
      computation automatically implements Bayesian Ockham razor that trades off
      between data-fitting and model complexity, which penalizes model classes that
      "over-fit" the data. The results of FE model updating and assessment based on the
      real data using the proposed method show that the updated FE model can
      successfully predict modal properties of the structural system with high
      accuracy.

PMID- 30213095
TI  - Potassium Citrate Supplementation Decreases the Biochemical Markers of Bone Loss
      in a Group of Osteopenic Women: The Results of a Randomized, Double-Blind,
      Placebo-Controlled Pilot Study.
AB  - The relationship involving acid-base imbalance, mineral metabolism and bone
      health status has previously been reported but the efficacy of the alkalizing
      supplementation in targeting acid overload and preventing bone loss has not yet
      been fully elucidated. In this randomized, double-blind, placebo-controlled
      study, the hypothesis that potassium citrate (K citrate) modifies bone turnover
      in women with postmenopausal osteopenia was tested. Three hundred and ten women
      were screened; 40 women met the inclusion criteria and were randomly assigned to
      the treatment or the placebo group. They were treated with K citrate (30 mEq day
      1) or a placebo in addition to calcium carbonate (500 mg day-1) and vitamin D
      (400 IU day-1). At baseline and time points of 3 and 6 months, serum indicators
      of renal function, electrolytes, calciotropic hormones, serum bone turnover
      markers (BTMs), tartrate-resistant acid phosphatase 5b (TRACP5b), carboxy
      terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (BAP),
      procollagen type 1 N terminal propeptide (PINP)), and urine pH, electrolytes, and
      citrate were measured. The follow-up was completed by 17/20 patients in the "K
      citrate" group and 18/20 patients in the "placebo" group. At baseline, 90% of the
      patients exhibited low potassium excretion in 24 h urine samples, and 85% of
      cases had at least one urine parameter associated with low-grade acidosis (low
      pH, low citrate excretion). After treatment, CTX and BAP decreased significantly
      in both groups, but subjects with evidence of low-grade acidosis gained
      significant benefits from the treatment compared to the placebo. In patients with
      low 24h-citrate excretion at baseline, a 30% mean decrease in BAP and CTX was
      observed at 6 months. A significant reduction was also evident when low citrate
      (BAP: -25%; CTX: -35%) and a low pH (BAP: -25%; CTX: -30%) were found in fasting
      morning urine. In conclusion, our results suggested that K citrate
      supplementation improved the beneficial effects of calcium and vitamin D in
      osteopenic women with a documented potassium and citrate deficit, and a metabolic
      profile consistent with low-grade acidosis.

PMID- 30213097
TI  - A KPI-Based Probabilistic Soft Sensor Development Approach that Maximizes the
      Coefficient of Determination.
AB  - Advanced technology for process monitoring and fault diagnosis is widely used in
      complex industrial processes. An important issue that needs to be considered is
      the ability to monitor key performance indicators (KPIs), which often cannot be
      measured sufficiently quickly or accurately. This paper proposes a data-driven
      approach based on maximizing the coefficient of determination for probabilistic
      soft sensor development when data are missing. Firstly, the problem of missing
      data in the training sample set is solved using the expectation maximization (EM)
      algorithm. Then, by maximizing the coefficient of determination, a probability
      model between secondary variables and the KPIs is developed. Finally, a Gaussian
      mixture model (GMM) is used to estimate the joint probability distribution in the
      probabilistic soft sensor model, whose parameters are estimated using the EM
      algorithm. An experimental case study on the alumina concentration in the
      aluminum electrolysis industry is investigated to demonstrate the advantages and
      the performance of the proposed approach.

PMID- 30213098
TI  - EasyLB: Adaptive Load Balancing Based on Flowlet Switching for Wireless Sensor
      Networks.
AB  - Load balancing is effective in reducing network congestion and improving network
      throughput in wireless sensor networks (WSNs). Due to the fluctuation of wireless
      channels, traditional schemes achieving load balancing in WSNs need to maintain
      global or local congestion information, which turn out to be complicated to
      implement. In this paper, we design a flowlet switching based load balancing
      scheme, called EasyLB, by extending OpenFlow protocol. Flowlet switching is
      efficient to achieve adaptive load balancing in WSNs. Nevertheless, one tricky
      problem lies in determining the flowlet timeout value, delta . Setting it too
      small would risk reordering issue, while setting it too large would reduce
      flowlet opportunities. By formulating the timeout setting problem with a
      stationary distribution of Markov chain, we give a theoretical reference for
      setting an appropriate timeout value in flowlet switching based load balancing
      scheme. Moreover, non-equal probability path selection and multiple parallel load
      balancing paths are considered in timeout setting problem. Experimental results
      show that, by setting timeout value following the preceding theoretical
      reference, EasyLB is adaptive to wireless channel condition change and achieves
      fast convergence of load balancing after link failures.

PMID- 30213099
TI  - Effects of Mining Activities on the Release of Heavy Metals (HMs) in a Typical
      Mountain Headwater Region, the Qinghai-Tibet Plateau in China.
AB  - Understanding the heavy metal (HM) contamination in alpine mountain headwaters
      regions is important to maintaining the ecosystem stability of the basin. A total
      of 119 water samples and 104 sediment samples were collected along tributaries
      and the main course of Heihe River. The concentrations of eight heavy metals (As,
      Cd, Cr, Cu, Mn, Ni, Pb, and Zn) in water and sediment were measured to describe
      their spatial variability and to assess water quality. To identify the origins
      and pathways of HMs, anions, cations, and trace elements, as well as
      deltaD/delta18O stable isotopes in water samples were also measured. The results
      of water quality assessment suggested that tributaries were affected by local
      mining activity. Factor analysis in sediments showed that all HMs in sediments
      were inherited from the parent bedrock. Both natural weathering and mining
      contribute HMs. Cr and Ni were homologous with a source from the weathering of
      basic gabbro and serpentine at Yushigou. Mn appeared to be influenced more by
      artificial activities such as agriculture and grazing. Depending on the mining
      technique involved, two pathways for the release of HMs were distinguished in
      this area. For open-pit mining, mining promoted the release of HMs primarily via
      enhanced weathering. For underground mining, HMs might have contributed to
      greater acid mine discharge at high elevations due to the weak weathering
      processes. As the elevation decreases, precipitation increases, and a series of
      complex hydrological factor significantly affect leaching and runoff. The study
      results can be applied to improve water management efficiency.

PMID- 30213100
TI  - Distorter Characterisation Using Mutual Inductance in Electromagnetic Tracking.
AB  - Electromagnetic tracking (EMT) is playing an increasingly important role in
      surgical navigation, medical robotics and virtual reality development as a
      positional and orientation reference. Though EMT is not restricted by line-of
      sight requirements, measurement errors caused by magnetic distortions in the
      environment remain the technology's principal shortcoming. The characterisation,
      reduction and compensation of these errors is a broadly researched topic, with
      many developed techniques relying on auxiliary tracking hardware including
      redundant sensor arrays, optical and inertial tracking systems. This paper
      describes a novel method of detecting static magnetic distortions using only the
      magnetic field transmitting array. An existing transmitter design is modified to
      enable simultaneous transmission and reception of the generated magnetic field. A
      mutual inductance model is developed for this transmitter design in which
      deviations from control measurements indicate the location, magnitude and
      material of the field distorter to an approximate degree. While not directly
      compensating for errors, this work enables users of EMT systems to optimise
      placement of the magnetic transmitter by characterising a distorter's effect
      within the tracking volume without the use of additional hardware. The
      discrimination capabilities of this method may also allow researchers to apply
      material-specific compensation techniques to minimise position error in the
      clinical setting.

PMID- 30213103
TI  - Bilateral Asymmetries in Ultrasound Assessments of the Rectus Femoris throughout
      an NCAA Division I Volleyball Preseason.
AB  - The purpose of the study was to assess glycogen content of the rectus femoris
      (RF) muscles utilizing high-frequency ultrasound throughout an intensive, nine
      day preseason training period in NCAA division I volleyball athletes. In the
      morning prior to the beginning of practice, athletes (n = 13) left and right RF
      muscles were assessed via ultrasound to quantify muscle fuel ratings (0-100 score
      range). The recommended location of the RF ultrasound scans were based on
      manufacturer guidelines, and the same technician recorded the daily measurements.
      To assess daily training load, session ratings of perceived exertion (s-RPE) were
      utilized. A paired t-test revealed a large significant difference between left
      (51.7 +/- 17.9) and right (32.8 +/- 17.4) RF muscle fuel ratings (p < 0.001).
      There was also a major effect of time on s-RPE (p < 0.001) and left (dominant) RF
      fuel rating (p = 0.001). s-RPE decreased from the beginning to the end of the
      training camp. However, left RF fuel ratings increased from the first to the
      second day, then remained elevated all throughout the preseason. In conclusion,
      all athletes were left-leg dominant and had a 57.6% bilateral asymmetry between
      their left and right RF muscle fuel ratings despite changes in training load.
      High-frequency ultrasounds are a noninvasive assessment tool that can determine
      glycogen replenishment asymmetries in the RF.

PMID- 30213102
TI  - Algal Viruses: The (Atomic) Shape of Things to Come.
AB  - Visualization of algal viruses has been paramount to their study and
      understanding. The direct observation of the morphological dynamics of infection
      is a highly desired capability and the focus of instrument development across a
      variety of microscopy technologies. However, the high temporal (ms) and spatial
      resolution (nm) required, combined with the need to operate in physiologically
      relevant conditions presents a significant challenge. Here we present a short
      history of virus structure study and its relation to algal viruses and highlight
      current work, concentrating on electron microscopy and atomic force microscopy,
      towards the direct observation of individual algae-virus interactions. Finally,
      we make predictions towards future algal virus study direction with particular
      focus on the exciting opportunities offered by modern high-speed atomic force
      microscopy methods and instrumentation.

PMID- 30213101
TI  - NLRP3 Inflammasome and IL-33: Novel Players in Sterile Liver Inflammation.
AB  - In sterile liver inflammation, danger signals are released in response to tissue
      injury to alert the immune system; e.g., by activation of the NLRP3 inflammasome.
      Recently, IL-33 has been identified as a novel type of danger signal or
      "alarmin", which is released from damaged and necrotic cells. IL-33 is a
      pleiotropic cytokine that targets a broad range of immune cells and exhibits pro-
      and anti-inflammatory properties dependent on the disease. This review summarizes
      the immunomodulatory roles of the NLRP3 inflammasome and IL-33 in sterile liver
      inflammation and highlights potential therapeutic strategies targeting these
      pathways in liver disease.

PMID- 30213104
TI  - Dietary Cows' Milk Protein A1 Beta-Casein Increases the Incidence of T1D in NOD
      Mice.
AB  - The contribution of cows' milk containing beta-casein protein A1 variant to the
      development of type 1 diabetes (T1D) has been controversial for decades. Despite
      epidemiological data demonstrating a relationship between A1 beta-casein
      consumption and T1D incidence, direct evidence is limited. We demonstrate that
      early life exposure to A1 beta-casein through the diet can modify progression to
      diabetes in non-obese diabetic (NOD) mice, with the effect apparent in later
      generations. Adult NOD mice from the F0 generation and all subsequent generations
      (F1 to F4) were fed either A1 or A2 beta-casein supplemented diets. Diabetes
      incidence in F0-F2 generations was similar in both cohorts of mice. However,
      diabetes incidence doubled in the F3 generation NOD mice fed an A1 beta-casein
      supplemented diet. In F4 NOD mice, subclinical insulitis and altered glucose
      handling was evident as early as 10 weeks of age in A1 fed mice only. A
      significant decrease in the proportion of non-conventional regulatory T cell
      subset defined as CD4+CD25-FoxP3+ was evident in the F4 generation of A1 fed
      mice. This feeding intervention study demonstrates that dietary A1 beta-casein
      may affect glucose homeostasis and T1D progression, although this effect takes
      generations to manifest.

PMID- 30213105
TI  - Primary Structure Analysis of Antifungal Peptides from Cultivated and Wild
      Cereals.
AB  - Cereal-derived bioactive peptides with antimicrobial activity have been poorly
      explored compared to those from dicotyledonous plants. Furthermore, there are a
      few reports addressing the structural differences between antimicrobial peptides
      (AMPs) from cultivated and wild cereals, which may shed light on significant
      varieties in the range and level of their antimicrobial activity. We performed a
      primary structure analysis of some antimicrobial peptides from wild and
      cultivated cereals to find out the features that are associated with the much
      higher antimicrobial resistance characteristic of wild plants. In this review, we
      identified and analyzed the main parameters determining significant antifungal
      activity. They relate to a high variability level in the sequences of C-terminal
      fragments and a high content of hydrophobic amino acid residues in the
      biologically active defensins in wild cereals, in contrast to AMPs from
      cultivated forms that usually exhibit weak, if any, activity. We analyzed the
      similarity of various physicochemical parameters between thionins and defensins.
      The presence of a high divergence on a fixed part of any polypeptide that is
      close to defensins could be a determining factor. For all of the currently known
      hevein-like peptides of cereals, we can say that the determining factor in this
      regard is the structure of the chitin-binding domain, and in particular, amino
      acid residues that are not directly involved in intermolecular interaction with
      chitin. The analysis of amino acid sequences of alpha-hairpinins (hairpin-like
      peptides) demonstrated much higher antifungal activity and more specificity of
      the peptides from wild cereals compared with those from wheat and corn, which may
      be associated with the presence of a mini cluster of positively charged amino
      acid residues. In addition, at least one hydrophobic residue may be responsible
      for binding to the components of fungal cell membranes.

PMID- 30213106
TI  - Newcastle Disease Virus V Protein Promotes Viral Replication in HeLa Cells
      through the Activation of MEK/ERK Signaling.
AB  - Newcastle disease virus (NDV) can infect a wide range of domestic and wild bird
      species. The non-structural V protein of NDV plays an important role in
      antagonizing innate host defenses to facilitate viral replication. However, there
      is a lack of knowledge related to the mechanisms through which the V protein
      regulates viral replication. The extracellular signal-regulated kinase (ERK)
      signaling pathway in the host is involved in a variety of functions and is
      activated by several stimuli, including viral replication. In this study, we show
      that both the lentogenic strain, La Sota, and the velogenic strain, F48E9, of NDV
      activate the mitogen-activated protein kinase (MEK)/ERK signaling pathway. The
      pharmacological inhibition of ERK1/2 phosphorylation using the highly selective
      inhibitors U0126 and SCH772984 resulted in the reduced levels of NDV RNA in cells
      and virus titers in the cell supernatant, which established an important role for
      the MEK/ERK signaling pathway in NDV replication. Moreover, the overexpression of
      the V protein in HeLa cells increased the phosphorylation of ERK1/2 and induced
      the transcriptional changes in the genes downstream of the MEK/ERK signaling
      pathway. Taken together, our results demonstrate that the V protein is involved
      in the ERK signaling pathway-mediated promotion of NDV replication and thus, can
      be investigated as a potential antiviral target.

PMID- 30213107
TI  - Norepinephrine Administration Is Associated with Higher Mortality in Dialysis
      Requiring Acute Kidney Injury Patients with Septic Shock.
AB  - (1) Background: Norepinephrine (NE) is the first-line vasoactive agent used in
      septic shock patients; however, the effect of norepinephrine on dialysis-required
      septic acute kidney injury (AKI-D) patients is uncertain. (2) Methods: To
      evaluate the impact of NE on 90-day mortality and renal recovery in septic AKI-D
      patients, we enrolled patients in intensive care units from 30 hospitals in
      Taiwan. (3) Results: 372 patients were enrolled and were divided into
      norepinephrine users and non-users. After adjustment by Inverse probability of
      treatment weighted (IPTW), there was no significant difference of baseline
      comorbidities between the two groups. NE users had significantly higher 90-day
      mortality rate and using NE is a strong predictor of 90-day mortality in the
      multivariate Cox regression (HR = 1.497, p = 0.027) after adjustment. The
      generalized additive model disclosed norepinephrine alone exerted a dose
      dependent effect on 90-day mortality, while other vasoactive agents were not. (4)
      Conclusion: Using norepinephrine in septic AKI-D patients is associated with
      higher 90-day mortality and the effect is dose-dependent. Further study to
      explore the potential mechanism is needed.

PMID- 30213109
TI  - Semi-Supervised Segmentation Framework Based on Spot-Divergence Supervoxelization
      of Multi-Sensor Fusion Data for Autonomous Forest Machine Applications.
AB  - In this paper, a novel semi-supervised segmentation framework based on a spot
      divergence supervoxelization of multi-sensor fusion data is proposed for
      autonomous forest machine (AFMs) applications in complex environments. Given the
      multi-sensor measuring system, our framework addresses three successive steps:
      firstly, the relationship of multi-sensor coordinates is jointly calibrated to
      form higher-dimensional fusion data. Then, spot-divergence supervoxels
      representing the size-change property are given to produce feature vectors
      covering comprehensive information of multi-sensors at a time. Finally, the
      Gaussian density peak clustering is proposed to segment supervoxels into sematic
      objects in the semi-supervised way, which non-requires parameters preset in
      manual. It is demonstrated that the proposed framework achieves a balancing act
      both for supervoxel generation and sematic segmentation. Comparative experiments
      show that the well performance of segmenting various objects in terms of
      segmentation accuracy (F-score up to 95.6%) and operation time, which would
      improve intelligent capability of AFMs.

PMID- 30213108
TI  - Antioxidant Activity and Neuroprotective Activity of Stilbenoids in Rat Primary
      Cortex Neurons via the PI3K/Akt Signalling Pathway.
AB  - Antioxidant activity and neuroprotective activity of three stilbenoids, namely,
      trans-4-hydroxystilbene (THS), trans-3,5,4'-trihydroxy-stilbene (resveratrol,
      RES), and trans-3',4',3,5-tetrahydroxy-stilbene (piceatannol, PIC), against beta
      amyloid (Abeta)-induced neurotoxicity in rat primary cortex neurons were
      evaluated. THS, RES, and PIC significantly scavenged DPPH* and *OH radicals. All
      three stilbenoids were able to inhibit Abeta neurotoxicity by decreasing
      intracellular reactive oxygen species (ROS) via the PI3K/Akt signalling pathway.
      Specifically, stilbenoids significantly promoted Akt phosphorylation; suppressed
      Bcl-2/Bax expression; and inhibited caspase-9, caspase-3, and PARP cleavage.
      Molecular docking between stilbenoids with Akt indicated that stilbenoids could
      form hydrogen bond interactions with the COOH-terminal region of Akt.
      Additionally, the neuroprotective activity of stilbenoids correlated with the
      number and position of hydroxyl groups. The lack of meta-dihydroxyl groups on THS
      did not affect its neuroprotective activity in comparison with RES, whereas the
      ortho-dihydroxyl moiety on PIC significantly enhanced neuroprotective activity.
      These results provide new insights into the correlation between the biological
      activity and chemical structure of stilbenoids.

PMID- 30213110
TI  - Robust Directional Angle Estimation of Underwater Acoustic Sources Using a Marine
      Vehicle.
AB  - Acoustic source localization is used in many underwater applications. Acquiring
      an accurate directional angle for an acoustic source is crucial for source
      localization. To achieve this purpose, this paper presents a method for
      directional angle estimation of underwater acoustic sources using a marine
      vehicle. It is assumed that the vehicle is equipped with two hydrophones and that
      the acoustic source transmits a specific signal repeatedly. The proposed method
      provides a probabilistic model for time delay estimation. The probability is
      recursively updated by prediction and update steps. The prediction step performs
      a probability transition using the angular displacement of the marine vehicle.
      The predicted probability is updated using a generalized cross correlation
      function with a verification process using entropy measurement. The proposed
      method can provide a reliable and accurate estimation of the directional angles
      of underwater acoustic sources. Experimental results demonstrate good performance
      of the proposed probabilistic directional angle estimation method in both an
      inland water environment and a harbor environment.

PMID- 30213111
TI  - Display in the Wild (DIW): An Adaptive Projection-Imaging System to Screen
      Geometry in Real Time.
AB  - TVs and monitors are among the most widely used displays in various environments.
      However, they have limitations in their physical display conditions, such as a
      fixed size/position and a rigid/flat space. In this paper, we suggest a new
      "Display in the Wild" (DIW) concept to overcome the aforementioned problems. Our
      proposed DIW system allows us to display a flexibly large screen on dynamic non
      planar surfaces at an arbitrary display position. To implement our DIW concept
      practically, we choose a projector as the hardware configuration in order to
      generate a screen anywhere with different sizes. However, distortion occurs when
      the projector displays content on a surface that is dynamic and/or non-planar.
      Therefore, we propose a distortion correction method for DIW to overcome the
      aforementioned surface constraints. Since projectors are not capture devices, we
      propose using a depth camera to determine the distortions on the surfaces
      quickly. We also propose DIW-specific calibration and fast/precise correction
      methods. Our calibration method is constructed to detect the projection surface
      easily and quickly, and also allows our proposed system to accommodate the
      intrinsic parameters such as a display resolution and field of view. We
      accomplish a fast undistortion process of the projector by considering only
      surface boundary pixels, which enables our method to run in real time. In our
      comprehensive experiments, the proposed DIW system generates undistorted screens
      such as TVs and monitors on dynamic non-planar surfaces at an arbitrary display
      position with Unmanned Aerial Vehicles (UAVs) in a fast and accurate manner,
      demonstrating its usefulness in practical DIW scenarios.

PMID- 30213112
TI  - Identification of Bioactive Chemical Markers in Zhi zhu xiang Improving Anxiety
      in Rat by Fingerprint-Efficacy Study.
AB  - Zhi zhu xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi
      Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood
      disorders for more than 2000 years, especially anxiety. The aim of the present
      work was to identify the bioactive chemical markers in Zhi zhu xiang improving
      anxiety in rats by a fingerprint-efficacy study. More specifically, the chemical
      fingerprint of ZZX samples collected from 10 different regions was determined by
      High Performance Liquid Chromatography (HPLC) and the similarity analyses were
      calculated based on 10 common characteristic peaks. The anti-anxiety effect of
      ZZX on empty bottle stimulated rats was examined through the Open Field Test
      (OFT) and the Elevated Plus Maze Test (EPM). Then we measured the concentration
      of CRF, ACTH, and CORT in rat's plasma by the enzyme-linked immune sorbent assay
      (ELISA) kit, while the concentration of monoamine and metabolites (NE, DA, DOPAC,
      HVA, 5-HT, 5-HIAA) in the rat's cerebral cortex and hippocampus was analysed by
      HPLC coupled with an Electrochemical Detector. At last, the fingerprint-efficacy
      study between chemical fingerprint and anti-anxiety effect of ZZX was
      accomplished by partial least squares regression (PLSR). As a result, we screened
      out four compounds (hesperidin, isochlorogenic acid A, isochlorogenic acid B and
      isochlorogenic acid C) as the bioactive chemical markers for the anti-anxiety
      effect of ZZX. The fingerprint-efficacy study we established might provide a
      feasible way and some elicitation for the identification of the bioactive
      chemical markers for TCM.

PMID- 30213115
TI  - Grain Boundary Segregation in Pd-Cu-Ag Alloys for High Permeability Hydrogen
      Separation Membranes.
AB  - Dense metal membranes that are based on palladium (Pd) are promising for hydrogen
      separation and production due to their high selectivity and permeability.
      Optimization of alloy composition has normally focused on bulk properties, but
      there is growing evidence that grain boundaries (GBs) play a crucial role in the
      overall performance of membranes. The present study provides parameters and
      analyses of GBs in the ternary Pd-Ag-Cu system, based on first-principles
      electronic structure calculations. The segregation tendency of Cu, Ag, and
      vacancies towards 12 different coherent ? GBs in Pd was quantified using three
      different procedures for relaxation of supercell lattice constants, representing
      the outer bounds of infinitely elastic and stiff lattice around the GBs. This
      demonstrated a clear linear correlation between the excess volume and the GB
      energy when volume relaxation was allowed for. The point defects were attracted
      by most of the GBs that were investigated. Realistic atomic-scale models of
      binary Pd-Cu and ternary Pd-Cu-Ag alloys were created for the ?5(210) boundary,
      in which the strong GB segregation tendency was affirmed. This is a starting
      point for more targeted engineering of alloys and grain structure in dense metal
      membranes and related systems.

PMID- 30213113
TI  - Alterations of Signaling Pathways Related to the Immune System in Breast Cancer:
      New Perspectives in Patient Management.
AB  - In recent years, immune manipulation for cancer treatment, including breast
      cancer, has been increasingly gaining consent, and many attempts have been made,
      mainly by either strengthening the immune response (IR) or by inhibiting immune
      evasion. Therefore, elucidating the related mechanisms is of importance due to
      the potential to improve the management of cancer patients by immunotherapy. This
      review article summarized some recent experimental studies, which have discovered
      novel alterations of signaling pathways related to the immune system in breast
      cancer. These altered signaling pathways have been grouped according to the
      general biological mechanism involved: tumor-initiating cells (TICs), cancer stem
      cells (CSCs), immune evasion, tumor growth and progression, prediction of
      clinical outcome and prediction of response, or resistance to chemotherapy. These
      altered pathways related to the immune system open clinical opportunities for the
      prognosis or treatment of patients. Many of these pathways are related to the
      origin of breast cancer and immune evasion. We recommended development of new
      drugs which act on these molecular pathways, and the designing of clinical trials
      to be carried out mainly in breast cancer patients who required adjuvant
      treatment.

PMID- 30213114
TI  - Obesity Proteomics: An Update on the Strategies and Tools Employed in the Study
      of Human Obesity.
AB  - Proteomics has become one of the most important disciplines for characterizing
      cellular protein composition, building functional linkages between protein
      molecules, and providing insight into the mechanisms of biological processes in a
      high-throughput manner. Mass spectrometry-based proteomic advances have made it
      possible to study human diseases, including obesity, through the identification
      and biochemical characterization of alterations in proteins that are associated
      with it and its comorbidities. A sizeable number of proteomic studies have used
      the combination of large-scale separation techniques, such as high-resolution two
      dimensional gel electrophoresis or liquid chromatography in combination with mass
      spectrometry, for high-throughput protein identification. These studies have
      applied proteomics to comprehensive biochemical profiling and comparison studies
      while using different tissues and biological fluids from patients to demonstrate
      the physiological or pathological adaptations within their proteomes. Further
      investigations into these proteome-wide alterations will enable us to not only
      understand the disease pathophysiology, but also to determine signature proteins
      that can serve as biomarkers for obesity and related diseases. This review
      examines the different proteomic techniques used to study human obesity and
      discusses its successful applications along with its technical limitations.

PMID- 30213116
TI  - A Method of HBase Multi-Conditional Query for Ubiquitous Sensing Applications.
AB  - Big data gathered from real systems, such as public infrastructure, healthcare,
      smart homes, industries, and so on, by sensor networks contain enormous value,
      and need to be mined deeply, which depends on a data storing and retrieving
      service. HBase is playing an increasingly important part in the big data
      environment since it provides a flexible pattern for storing extremely large
      amounts of unstructured data. Despite the fast-speed reading by RowKey, HBase
      does not natively support multi-conditional query, which is a common demand and
      operation in relational databases, especially for data analysis of ubiquitous
      sensing applications. In this paper, we introduce a method to construct a linear
      index by employing a Hilbert space-filling curve. As a RowKey generating schema,
      the proposed method maps multiple index-columns into a one-dimensional encoded
      sequence, and then constructs a new RowKey. We also provide a R-tree-based
      optimization to reduce the computational cost of encoding query conditions.
      Without using a secondary index mode, experimental results indicate that the
      proposed method has better performance in multi-conditional queries.

PMID- 30213117
TI  - Association of Pre-Eclampsia with Carotid Artery Intima-Media Thickness and Non
      Alcoholic Fatty Liver Disease.
AB  - Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are considered
      important complications of pre-eclampsia. This study was conducted to determine
      the association of pre-eclampsia with non-alcoholic fatty liver disease and the
      association of pre-eclampsia with bilateral intima-media thickness (IMT; right
      and left), separately. Twenty-one pregnant women with pre-eclampsia and 21 normal
      pregnant women were enrolled in the present study. The right and left intima
      media thicknesses of carotid arteries were evaluated using Doppler sonography.
      The diagnosis of NAFLD was based on sonography. Linear and binary logistic
      regression analyses were performed to evaluate the association between pre
      eclampsia and related outcomes. The mean right IMT was determined as 0.60 +/-
      0.07 mm in women with pre-eclampsia and 0.51 +/- 0.08 mm in normal pregnant women
      (p = 0.001). On the other hand, the mean left IMT was 0.59 +/- 0.09 mm in women
      with pre-eclampsia and 0.50 +/- 0.10 mm in normal pregnant women (p = 0.003). The
      frequencies of NAFLD in women with pre-eclampsia and normal pregnant women were
      found to be 66.7% and 23.8% respectively (p = 0.006). Multivariate linear
      regression analysis revealed an association between pre-eclampsia and right (p =
      0.014) and left (p = 0.019) IMT, without removing the effects of other
      confounding variables. Binary regression analysis (multivariate) did not confirm
      an independent association between pre-eclampsia and NAFLD. Pre-eclampsia
      exhibited a direct and independent association with right and left IMT. Although
      the prevalence of NAFLD was significantly higher in women with pre-eclampsia, pre
      eclampsia was not an independent predictor for NAFLD.

PMID- 30213118
TI  - Monitoring and Assessing the Degradation Rate of Magnesium-Based Artificial Bone
      In Vitro Using a Wireless Magnetoelastic Sensor.
AB  - A magnetoelastic-based (MB) sensor was employed as a novel method to monitor and
      assess the degradation rate of magnesium-based artificial bone (MBAB) in vitro,
      which can be used as an implant to repair a bone defect, providing a quantitative
      method to depict the degradation rate of MBAB. MBABs were fabricated by the
      Pro/Engineering software and a precision machine tool using high-purity (HP)
      magnesium. The MB sensor was embedded in the neutral surface of MBAB by an
      unharmful quick adhesive, forming the MB sensor-embedded MBAB (EMBAB). The
      modified simulated body fluid (MSBF) media (PH = 7.4), mimicking the human
      internal environment, and the NaOH media (PH = 12), accelerating EMBAB's
      degradation, were used to immerse the EMBAB for 15 days at 37  degrees C. The
      EMBAB was then tested daily on a self-developed experimental platform to monitor
      the relative output power under a 100 N external force. The results showed that
      the relative output power of the sensing coil gradually increased with the
      EMBAB's degradation. The degradation rate of the EMBAB could be calculated on the
      basis of the changes of the relative output power caused by the MB sensor and of
      the degradation time. With the EMBAB's degradation, an increasing strain directly
      worked on the MB sensor, significantly changing the value of the relative output
      power, which means that the EMBAB was characterized by a quick degradation rate.
      During the 15 days of the experiment, the degradation rates on the 7th and 15th
      days were 0.005 dbm/day and 0.02 dbm/day, and 0.02 dbm/day and 0.04 dbm/day in
      MSBF and alkaline media, respectively. Therefore, the MB sensor provides a
      wireless and passive method to monitor and assess the degradation rate of bone
      implants in vitro.

PMID- 30213119
TI  - Improving Electron Extraction Ability and Device Stability of Perovskite Solar
      Cells Using a Compatible PCBM/AZO Electron Transporting Bilayer.
AB  - Due to the low temperature fabrication process and reduced hysteresis effect,
      inverted p-i-n structured perovskite solar cells (PSCs) with the PEDOT:PSS as the
      hole transporting layer and PCBM as the electron transporting layer have
      attracted considerable attention. However, the energy barrier at the interface
      between the PCBM layer and the metal electrode, which is due to an energy level
      mismatch, limits the electron extraction ability. In this work, an inorganic
      aluminum-doped zinc oxide (AZO) interlayer is inserted between the PCBM layer and
      the metal electrode so that electrons can be collected efficiently by the
      electrode. It is shown that with the help of the PCBM/AZO bilayer, the power
      conversion efficiency of PSCs is significantly improved, with negligible
      hysteresis and improved device stability. The UPS measurement shows that the AZO
      interlayer can effectively decrease the energy offset between PCBM and the metal
      electrode. The steady state photoluminescence, time-resolved photoluminescence,
      transient photocurrent, and transient photovoltage measurements show that the
      PSCs with the AZO interlayer have a longer radiative carrier recombination
      lifetime and more efficient charge extraction efficiency. Moreover, the
      introduction of the AZO interlayer could protect the underlying perovskite, and
      thus, greatly improve device stability.

PMID- 30213120
TI  - Regeneration of Transected Recurrent Laryngeal Nerve Using Hybrid-Transplantation
      of Skeletal Muscle-Derived Stem Cells and Bioabsorbable Scaffold.
AB  - Hybrid transplantation of skeletal muscle-derived multipotent stem cells (Sk
      MSCs) and bioabsorbable polyglyconate (PGA) felt was studied as a novel
      regeneration therapy for the transected recurrent laryngeal nerve (RLN). Sk-MSCs
      were isolated from green fluorescence protein transgenic mice and then expanded
      and transplanted with PGA felt for the hybrid transplantation (HY group) into the
      RLN transected mouse model. Transplantation of culture medium (M group) and PGA +
      medium (PGA group) were examined as controls. After eight weeks, trans-oral video
      laryngoscopy demonstrated 80% recovery of spontaneous vocal-fold movement during
      breathing in the HY group, whereas the M and PGA groups showed wholly no
      recoveries. The Sk-MSCs showed active engraftment confined to the damaged RLN
      portion, representing favorable prevention of cell diffusion on PGA, with an
      enhanced expression of nerve growth factor mRNAs. Axonal re-connection in the HY
      group was confirmed by histological serial sections. Immunohistochemical analysis
      revealed the differentiation of Sk-MSCs into Schwann cells and
      perineurial/endoneurial cells and axonal growth supportive of
      perineurium/endoneurium. The number of axons recovered was over 86%. These
      results showed that the stem cell and cytokine delivery system using hybrid
      transplantation of Sk-MSCs/PGA-felt is a potentially practical and useful
      approach for the recovery of transected RLN.

PMID- 30213121
TI  - Out-of-Band Response for the Coastal Zone Imager (CZI) Onboard China's Ocean
      Color Satellite HY-1C: Effect on the Observation Just above the Sea Surface.
AB  - The out-of-band (OOB) response is one of the key specifications for satellite
      optical sensors, which has important influences on quantitative remote sensing
      retrieval. In this paper, the effect of OOB response on the radiometric
      measurements made just above the sea surface is evaluated for the three broad
      visible bands (i.e., blue, green, and red) of the Coastal Zone Imager (CZI)
      onboard China's ocean satellite HY-1C to be launched in September 2018. For the
      turbid coastal (Case 2) waters whose optical properties are mainly dominated by
      suspended sediment and colored dissolved organic material, the OOB effect can be
      neglected (<2%) for all three CZI visible bands. For the phytoplankton-dominated
      (Case 1) waters which are mainly distributed in the clear open ocean, a
      significant (>2%) OOB effect was found in the green band over oligotrophic waters
      (chlorophyll a concentration <=~0.1 mg/m3), and accordingly a model based on the
      CZI blue-green band ratio is proposed to correct this effect. The OOB influence
      on the CZI ocean color retrieval is discussed. This research highlights the
      importance of the comprehensive pre-launch radiometric characterization and the
      OOB effect correction for the broad band space-borne sensor, in order to achieve
      a high-quality quantitative ocean product.

PMID- 30213122
TI  - Experimental Study of Wireless Monitoring of Human Respiratory Movements Using
      UWB Impulse Radar Systems.
AB  - This paper analyzes and discusses the capability of human being detection using
      impulse ultra-wideband (UWB) radar with an improved detection algorithm. The
      multiple automatic gain control (AGC) technique is employed to enhance the
      amplitudes of human respiratory signals. Two filters with seven values averaged
      are used to further improve the signal-to-noise ratio (SNR) of the human
      respiratory signals. The maximum slope and standard deviation are used for
      analyzing the characteristics of the received pulses, which can provide two
      distance estimates for human being detection. Most importantly, based on the two
      distance estimates, we can accurately judge whether there are human beings in the
      detection environments or not. The data size can be reduced based on the defined
      interested region, which can improve the operation efficiency of the radar system
      for human being detection. The developed algorithm provides excellent performance
      regarding human being detection, which is validated through comparison with
      several well-known algorithms.

PMID- 30213123
TI  - Synthesis of Spirooxindole-O-Naphthoquinone-Tetrazolo[1,5-a]Pyrimidine Hybrids as
      Potential Anticancer Agents.
AB  - A series of novel spirooxindole-O-naphthoquinone-tetrazolo[1,5-a]pyrimidine
      hybrids were designed, synthesized and evaluated as potent antitumor agents.
      These hybrids exhibited relatively high cytotoxic activity against cancer cell
      line HepG2 (IC50 = 2.86-36.34 MUM), while normal cell line LO2 was less sensitive
      to these hybrids (IC50 = 36.37-248.39 MUM). On the whole, among all the compounds
      tested, compound 4e, with a mean IC50 value of 2.86 MUM, was the most active. The
      novel hybrids may find their pharmaceutical applications after further
      investigations.

PMID- 30213124
TI  - Endocannabinoid Metabolome Characterization of Transitional and Mature Human
      Milk.
AB  - Recognized as the gold standard, human milk (HM) is an extremely complex yet
      fascinating biofluid tailored to meet an infant's nutritional requirements
      throughout development. Endocannabinoids and endocannabinoid-like compounds
      (endocannabinoid metabolome, ECM) are endogenous lipid mediators derived from
      long-chain polyunsaturated fatty acids that have been identified in HM. Previous
      research has shown that arachidonoylglycerol might play a role in establishing
      the infant's suckling response during lactation by activating the type 1
      cannabinoid receptor in the infant's brain. The mechanisms of action and the role
      of the ECM in HM are not fully understood. Transitional and mature milk samples
      were collected from lactating women (n = 24) for ECM characterization,
      quantification, and to evaluate differences among the two stages. HM samples were
      analyzed by liquid chromatography-mass spectrometry. Identified members of the
      ECM were: arachidonoylethanolamine, palmitoylethanolamine, oleoylethanolamine,
      docosahexaenoylethanolamine, eicoapentaenoylethanolamine, eicosenoylethanolamine,
      arachidonoylglycerol, palmitoyglycerol, oleoylglycerol, docosahexaenoylglycerol,
      eicosapentaenoylglycerol, eiconenooylglycerol, arachidonic acid, docosahexaenoic
      acid, and eicosapentaenoic acid. Only docosahexaenoylglycerol was different
      across transitional and mature milk (p <= 0.05). Data from this cohort suggest
      that bioactive constituents in HM may also play a role in infant health and
      development. Future studies can be developed based on this study's data to help
      elucidate specific roles for each ECM member in addition to understanding how the
      ECM modulates infant health.

PMID- 30213125
TI  - Validation of Internal Control Genes for Quantitative Real-Time PCR Gene
      Expression Analysis in Morchella.
AB  - The reliability of qRT-PCR results depend on the stability of reference genes
      used for normalization, suggesting the necessity of identification of reference
      genes before gene expression analysis. Morels are edible mushrooms well-known
      across the world and highly prized by many culinary kitchens. Here, several
      candidate genes were selected and designed according to the Morchella importuna
      transcriptome data. The stability of the candidate genes was evaluated with
      geNorm and NormFinder under three different experimental conditions, and several
      genes with excellent stability were selected. The extensive adaptability of the
      selected genes was tested in ten Morchella species. Results from the three
      experimental conditions revealed that ACT1 and INTF7 were the most prominent
      genes in Morchella, CYC3 was the most stable gene in different development
      stages, INTF4/AEF3 were the top-ranked genes across carbon sources, while
      INTF3/CYC3 pair showed the robust stability for temperature stress treatment. We
      suggest using ACT1, AEF3, CYC3, INTF3, INTF4 and INTF7 as reference genes for
      gene expression analysis studies for any of the 10 Morchella strains tested in
      this study. The stability and practicality of the gene, vacuolar protein sorting
      (INTF3), vacuolar ATP synthase (INTF4) and14-3-3 protein (INTF7) involving the
      basic biological processes were validated for the first time as the candidate
      reference genes for quantitative PCR. Furthermore, the stability of the reference
      genes was found to vary under the three different experimental conditions,
      indicating the importance of identifying specific reference genes for particular
      conditions.

PMID- 30213126
TI  - Cell Group Recognition Method Based on Adaptive Mutation PSO-SVM.
AB  - The increased volume and complexity of flow cytometry (FCM) data resulting from
      the increased throughput greatly boosts the demand for reliable statistical
      methods for the analysis of multidimensional data. The Support Vector Machines
      (SVM) model can be used for classification recognition. However, the selection of
      penalty factor c and kernel parameter g in the model has a great influence on the
      correctness of clustering. To solve the problem of parameter optimization of the
      SVM model, a support vector machine algorithm of particle swarm optimization (PSO
      SVM) based on adaptive mutation is proposed. Firstly, a large number of FCM data
      were used to carry out the experiment, and the kernel function adapted to the
      sample data was selected. Then the PSO algorithm of adaptive mutation was used to
      optimize the parameters of the SVM classifier. Finally, the cell clustering
      results were obtained. The method greatly improves the clustering correctness of
      traditional SVM. That also overcomes the shortcomings of PSO algorithm, which is
      easy to fall into local optimum in the iterative optimization process and has
      poor convergence effect in dealing with a large number of data. Compared with the
      traditional SVM algorithm, the experimental results show that, the correctness of
      the method is improved by 19.38%. Compared with the cross-validation algorithm
      and the PSO algorithm, the adaptive mutation PSO algorithm can also improve the
      correctness of FCM data clustering. The correctness of the algorithm can reach
      99.79% and the time complexity is relatively lower. At the same time, the method
      does not need manual intervention, which promotes the research of cell group
      identification in biomedical detection technology.

PMID- 30213127
TI  - Rapid Determination of the Oil and Moisture Contents in Camellia gauchowensis
      Chang and Camellia semiserrata Chi Seeds Kernels by Near-infrared Reflectance
      Spectroscopy.
AB  - A fast and effective determination method of different species of vegetable seeds
      oil is vital in the plant oil industry. The near-infrared reflectance
      spectroscopy (NIRS) method was developed in this study to analyze the oil and
      moisture contents of Camelliagauchowensis Chang and C.semiserrata Chi seeds
      kernels. Calibration and validation models were established using principal
      component analysis (PCA) and partial least squares (PLS) regression methods. In
      the prediction models of NIRS, the levels of accuracy obtained were sufficient
      for C.gauchowensis Chang and C.semiserrata Chi, the correlation coefficients of
      which for oil were 0.98 and 0.95, respectively, and those for moisture were 0.92
      and 0.89, respectively. The near infrared spectrum of crush seeds kernels was
      more precise compared to intact kernels. Based on the calibration models of the
      two Camellia species, the NIRS predictive oil contents of C.gauchowensis Chang
      and C.semiserrata Chi seeds kernels were 48.71 +/- 8.94% and 58.37 +/- 7.39%, and
      the NIRS predictive moisture contents were 4.39 +/- 1.08% and 3.49 +/- 0.71%,
      respectively. The NIRS technique could determine successfully the oil and
      moisture contents of C.gauchowensis Chang and C.semiserrata Chi seeds kernels.

PMID- 30213128
TI  - Learning-Directed Dynamic Voltage and Frequency Scaling Scheme with Adjustable
      Performance for Single-Core and Multi-Core Embedded and Mobile Systems.
AB  - Dynamic voltage and frequency scaling (DVFS) is a well-known method for saving
      energy consumption. Several DVFS studies have applied learning-based methods to
      implement the DVFS prediction model instead of complicated mathematical models.
      This paper proposes a lightweight learning-directed DVFS method that involves
      using counter propagation networks to sense and classify the task behavior and
      predict the best voltage/frequency setting for the system. An intelligent
      adjustment mechanism for performance is also provided to users under various
      performance requirements. The comparative experimental results of the proposed
      algorithms and other competitive techniques are evaluated on the NVIDIA JETSON
      Tegra K1 multicore platform and Intel PXA270 embedded platforms. The results
      demonstrate that the learning-directed DVFS method can accurately predict the
      suitable central processing unit (CPU) frequency, given the runtime statistical
      information of a running program, and achieve an energy savings rate up to 42%.
      Through this method, users can easily achieve effective energy consumption and
      performance by specifying the factors of performance loss.

PMID- 30213129
TI  - Chemical Constituents from Croton Species and Their Biological Activities.
AB  - The genus Croton belongs to the Euphorbiaceae family, which comprises
      approximately 1300 species. Many Croton species have been used as folk medicines.
      This review focuses on the chemical constituents from Croton species and their
      relevant biological activities, covering the period from 2006 to 2018. A total of
      399 new compounds, including 339 diterpenoids, were reported. Diterpenoids are
      characteristic components of the Croton species. These isolated compounds
      exhibited a broad spectrum of bioactivities, including cytotoxic, anti
      inflammatory, antifungal, acetylcholinesterase inhibitory, and neurite outgrowth
      promoting properties. The present review provides a significant clue for further
      research of the chemical constituents from the Croton species as potential
      medicines.

PMID- 30213131
TI  - Intelligent Ball Bearing Fault Diagnosis Using Fractional Lorenz Chaos Extension
      Detection.
AB  - In this study we used a non-autonomous Chua's circuit, and the fractional Lorenz
      chaos system. This was combined with the Extension theory detection method to
      analyze the voltage signals. The bearing vibration signals, measured using an
      acceleration sensor, were introduced into the master and slave systems through a
      Chua's circuit. In a chaotic system, minor differences can cause significant
      changes that generate dynamic errors. The matter-element model extension can be
      used to determine the bearing condition. Extension theory can be used to
      establish classical and sectional domains using the dynamic errors of the fault
      conditions. The results obtained were compared with those from discrete Fourier
      transform analysis, wavelet analysis and an integer order chaos system. The
      diagnostic rate of the fractional-order master and slave chaotic system could
      reach 100% if the fractional-order parameter adjustment was used. This study
      presents a very efficient and inexpensive method for monitoring the state of ball
      bearings.

PMID- 30213132
TI  - Study on the Magnetic-machine Coupling Characteristics of Giant Magnetostrictive
      Actuator Based on the Free Energy Hysteresis Characteristics.
AB  - A giant magnetostrictive actuator presents advantages such as large strain, high
      precision, and quick response. It is a hotly debated research topic in the field
      of micro drivers; however, the nonlinear intrinsic relationship between its
      output and input signals make it difficult to construct its nonlinear eigen model
      in the process of its practical application. Therefore, the motivation of this
      paper is to study the nonlinear magnetic-mechanical coupling characteristics of
      the giant magnetostrictive actuator, which is driven by free energy hysteresis
      characteristics. The nonlinear magnetic-mechanical coupling model under the weak
      form solution is deduced from the basic electromagnetic and mechanical theories,
      based on the distribution law of the axial magnetic field simulation, carried out
      to analyze the output displacement characteristics of the giant magnetostrictive
      actuator under preload. Experimental characterization of the device is also
      studied in the built experiment setup. Research results show that the
      experimental results coincide well with the simulation results, which show that
      the designed magnetic circuit for the giant magnetostrictive actuator is correct,
      and the coupling model of magnetic and machine of the giant magnetostrictive
      actuator based on the free energy hysteresis characteristics is reasonable.

PMID- 30213130
TI  - Suppressive Effects of EGCG on Cervical Cancer.
AB  - Cervical cancer is the fourth most common gynecological cancer worldwide.
      Although prophylactic vaccination presents the most effective method for cervical
      cancer prevention, chemotherapy is still the primary invasive intervention. It is
      urgent to exploit low-toxic natural anticancer drugs on account of high
      cytotoxicity and side-effects of conventional agents. As a natural product, (-)
      epigallocatechingallate (EGCG) has abilities in anti-proliferation, anti
      metastasis and pro-apoptosis of cervical cancer cells. Moreover, EGCG also has
      pharmaceutical synergistic effects with conventional agents such as cisplatin
      (CDDP) and bleomycin (BLM). The underlying mechanisms of EGCG suppressive effects
      on cervical cancer are reviewed in this article. Further research directions and
      ambiguous results are also discussed.

PMID- 30213133
TI  - Martial Arts as a Form of Undertaking Physical Activity in Leisure Time Analysis
      of Factors Determining Participation of Poles.
AB  - BACKGROUND: The aim of this paper was to analyze selected sociodemographic and
      economic factors that determine practicing martial arts (MA) in Poland. Our
      hypothesis states that MA constitute a niche sport, which is a result of
      conditions shaping the decision to undertake them: perception through the lens of
      the media/entertainment business (rather than primary values), insufficient space
      for practicing, as well as high costs. METHODS: The study was based on a survey
      conducted on a representative sample of Poles (n = 12,183). Results for 470
      participants declaring some level of proficiency in MA were presented (including
      124 declaring active participation). In order to verify statistically significant
      differences, a Chi-Square test, single-agent logistic regression analysis, and
      adds ratio were applied. RESULTS: 3.0% of respondents declared basic skills in
      MA, while advanced skills were declared by 0.9% participants. Only 1% were active
      practitioners. The leading motivation was "pleasure" (62.1%), followed by
      "keeping fit and maintaining healthy body shape" (21.8%) and "health" (7.3%). The
      probability of participation in MA decreased with age (40 years of age being the
      turning point). As for young people, there is a 15 times lower chance of married
      individuals undertaking MA, while possessing advanced skills doubles the
      probability. School provides a place to practice MA during school years, but
      there is a problem with continuation at a later age (18.8% declaring classes
      organized at school vs. 5.4% organized at work). CONCLUSIONS: Reversing the trend
      of decreasing popularity of MA requires promotion on each level of education and
      creating opportunities to continue participation after graduation. There is a
      need to increase the availability of cheap sport facilities in the vicinity of
      the place of residence or work. In case of adults, it is important to build
      platforms facilitating contact with MA centers.

PMID- 30213134
TI  - Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity.
AB  - Cyclin dependent kinase inhibitor 1c (Cdkn1c) is a maternally expressed imprinted
      gene with roles in embryonic development, post-natal metabolism and behaviour.
      Using mouse models with altered dosages of Cdkn1c, we have previously identified
      a role for the gene in promoting brown adipose tissue formation. Here, we use
      these transgenic mouse lines to model the loss of imprinting of Cdkn1c in
      adulthood. We demonstrate that only a two-fold increase in the expression of
      Cdkn1c during development is sufficient to protect against age-related weight
      gain in addition to glucose and insulin intolerance. Further to this, we show
      that the loss of imprinting of Cdkn1c protects against diet-induced obesity.
      Bisulphite sequencing was performed to test the stability of the two
      differentially methylated regions that regulate Cdkn1c imprinting, and both were
      found to be unaltered in aged or diet-challenged adipose tissue, despite drastic
      reductions in Cdkn1c expression. These data demonstrate a critical role for
      Cdkn1c in regulating adult adipose tissue, with modest changes in expression
      capable of protecting against both age and diet-induced obesity and metabolic
      syndrome, with a natural decline in Cdkn1c expression observed that may
      contribute to less healthy metabolic aging. Finally, we have observed a post
      natal insensitivity of the imprint to environmental factors, in contrast to
      recent observations of an in utero sensitivity.

PMID- 30213135
TI  - Blacks' Diminished Return of Education Attainment on Subjective Health; Mediating
      Effect of Income.
AB  - Background: Minorities' Diminished Return (MDR) can be defined as smaller health
      gains from socioeconomic status (SES) indicators, such as education attainment
      among ethnic minorities compared to the majority group. The current study tested
      whether income explains why Black and White adults differ in the association
      between education attainment and self-rated health (SRH). Methods: With a cross
      sectional design, this study used data from Cycle 5 of the Health Information
      National Trends Survey (HINTS), 2017. With a nationally representative sample,
      the HINTS study generates results that are generalizable to US adults. This study
      included 2277 adults who were either non-Hispanic White (n = 1868; 82%) or non
      Hispanic Black (n = 409; 18%). The independent variable was education attainment.
      The dependent variable was SRH, measured using a standard single item. Age,
      gender, and health insurance status were covariates. Ethnicity was the focal
      moderator. Income was the mediator. A structural equation model (SEM) was applied
      for data analysis. Results: Overall, higher education attainment was associated
      with better SRH, net of covariates. However, a significant interaction between
      ethnicity and education attainment suggested a smaller SRH gain from education
      for Blacks compared to Whites. This interaction could be explained by Black-White
      differences in income. Conclusion: Our study results suggests that labor market
      preferences may explain smaller effects of education attainment on SRH for Blacks
      relative to Whites. Given this finding and other studies documenting MDR,
      policies should reduce labor market discrimination, increasing job opportunities
      and reducing the racial pay gap for Blacks. Programs should help Blacks compete
      for prestigious and high-paying jobs.

PMID- 30213137
TI  - DM-MQTT: An Efficient MQTT Based on SDN Multicast for Massive IoT Communications.
AB  - Edge computing is proposed to solve the problem of centralized cloud computing
      caused by a large number of IoT (Internet of Things) devices. The IoT protocols
      need to be modified according to the edge computing paradigm, where the edge
      computing devices for analyzing IoT data are distributed to the edge networks.
      The MQTT (Message Queuing Telemetry Transport) protocol, as a data distribution
      protocol widely adopted in many international IoT standards, is suitable for
      cloud computing because it uses a centralized broker to effectively collect and
      transmit data. However, the standard MQTT may suffer from serious traffic
      congestion problem on the broker, causing long transfer delays if there are
      massive IoT devices connected to the broker. In addition, the big data exchange
      between the IoT devices and the broker decreases network capability of the edge
      networks. The authors in this paper propose a novel MQTT with a multicast
      mechanism to minimize data transfer delay and network usage for the massive IoT
      communications. The proposed MQTT reduces data transfer delays by establishing
      bidirectional SDN (Software Defined Networking) multicast trees between the
      publishers and the subscribers by means of bypassing the centralized broker. As a
      result, it can reduce transmission delay by 65% and network usage by 58% compared
      with the standard MQTT.

PMID- 30213138
TI  - Dose-Related Antihypertensive Properties and the Corresponding Mechanisms of a
      Chicken Foot Hydrolysate in Hypertensive Rats.
AB  - The antihypertensive properties of different doses of a chicken foot hydrolysate,
      Hpp11 and the mechanisms involved in this effect were investigated. Spontaneously
      hypertensive rats (SHR) were administered water, Captopril (50 mg/kg) or Hpp11 at
      different doses (25, 55 and 85 mg/kg), and the systolic blood pressure (SBP) was
      recorded. The SBP of normotensive Wistar-Kyoto (WKY) rats administered water or
      Hpp11 was also recorded. Additionally, plasmatic angiotensin-converting enzyme
      (ACE) activity was determined in the SHR administered Hpp11. Moreover, the
      relaxation caused by Hpp11 in isolated aortic rings from Sprague-Dawley rats was
      evaluated. Hpp11 exhibited antihypertensive activity at doses of 55 and 85 mg/kg,
      with maximum activity 6 h post-administration. At this time, no differences were
      found between these doses and Captopril. Initial SBP values of 55 and 85 mg/kg
      were recovered 24 or 8 h post-administration, respectively, 55 mg/kg being the
      most effective dose. At this dose, a reduction in the plasmatic ACE activity in
      the SHR was found. However, Hpp11 did not relax the aortic ring preparations.
      Therefore, ACE inhibition could be the mechanism underlying Hpp11
      antihypertensive effect. Remarkably, Hpp11 did not modify SBP in WKY rats,
      showing that the decreased SBP effect is specific to the hypertensive state.

PMID- 30213139
TI  - Novel Protein Kinase Inhibitors Related to Tau Pathology Modulate Tau Protein
      Self Interaction Using a Luciferase Complementation Assay.
AB  - The current number of drugs available for the treatment of Alzheimer's disease
      (AD) is strongly limited and their benefit for therapy is given only in the early
      state of the disease. An effective therapy should affect those processes which
      mainly contribute to the neuronal decay. There have been many approaches for a
      reduction of toxic Abeta peptides which mostly failed to halt cognitive
      deterioration in patients. The formation of neurofibrillary tangles (NFT) and its
      precursor tau oligomers have been suggested as main cause of neuronal
      degeneration because of a direct correlation of their density to the degree of
      dementia. Reducing of tau aggregation may be a viable approach for the treatment
      of AD. NFT consist of hyperphosphorylated tau protein and tau
      hyperphosphorylation reduces microtubule binding. Several protein kinases are
      discussed to be involved in tau hyperphosphorylation. We developed novel
      inhibitors of three protein kinases (gsk-3beta, cdk5, and cdk1) and discussed
      their activity in relation to tau phosphorylation and on tau-tau interaction as a
      nucleation stage of a tau aggregation in cells. Strongest effects were observed
      for those inhibitors with effects on all the three kinases with emphasis on gsk
      3beta in nanomolar ranges.

PMID- 30213140
TI  - Preparation, Characterization, and In Vivo Evaluation of an Oral Multiple
      Nanoemulsive System for Co-Delivery of Pemetrexed and Quercetin.
AB  - Co-administration of conventional and natural chemotherapeutics offers
      synergistic anticancer efficacy while minimizing adverse effects. In this study,
      an oral co-delivery system for pemetrexed (PMX) and quercetin (QCN) was designed
      based on water-in-oil-in-water nanoemulsion (NE), which is highly absorbable
      because it enhances the intestinal membrane permeability of PMX and aqueous
      solubility of QCN. To create this system, an ion-pairing complex of PMX with
      Nalpha-deoxycholyl-l-lysyl-methylester (DCK) was formed and further incorporated
      with QCN into the NE, yielding PMX/DCK-QCN-NE. The results revealed synergistic
      inhibitory effects on human lung carcinoma (A549) cell proliferation and
      migration after combined treatment with PMX/DCK and QCN. The intestinal membrane
      permeability and cellular uptake of PMX/DCK and QCN from the NE were
      significantly improved via facilitated transport of PMX by the interaction of DCK
      with bile acid transporters, as well as NE formulation-mediated alterations in
      the membrane structure and fluidity, which resulted in 4.51- and 23.9-fold
      greater oral bioavailability of PMX and QCN, respectively, than each free drug.
      Tumor growth in A549 cell-bearing mice was also maximally suppressed by 62.7%
      after daily oral administration of PMX/DCK-QCN-NE compared with controls. Thus,
      PMX/DCK-QCN-NE is a promising oral nanocarrier of PMX and QCN for synergistic
      anticancer efficacy and long-term chemotherapy.

PMID- 30213141
TI  - Development of a Prediction Model for Colorectal Cancer among Patients with Type
      2 Diabetes Mellitus Using a Deep Neural Network.
AB  - OBJECTIVES: Observational studies suggested that patients with type 2 diabetes
      mellitus (T2DM) presented a higher risk of developing colorectal cancer (CRC).
      The current study aims to create a deep neural network (DNN) to predict the onset
      of CRC for patients with T2DM. METHODS: We employed the national health insurance
      database of Taiwan to create predictive models for detecting an increased risk of
      subsequent CRC development in T2DM patients in Taiwan. We identified a total of
      1,349,640 patients between 2000 and 2012 with newly diagnosed T2DM. All the
      available possible risk factors for CRC were also included in the analyses. The
      data were split into training and test sets with 97.5% of the patients in the
      training set and 2.5% of the patients in the test set. The deep neural network
      (DNN) model was optimized using Adam with Nesterov's accelerated gradient
      descent. The recall, precision, F1 values, and the area under the receiver
      operating characteristic (ROC) curve were used to evaluate predictor performance.
      RESULTS: The F1, precision, and recall values of the DNN model across all data
      were 0.931, 0.982, and 0.889, respectively. The area under the ROC curve of the
      DNN model across all data was 0.738, compared to the ideal value of 1. The
      metrics indicate that the DNN model appropriately predicted CRC. In contrast, a
      single variable predictor using adapted the Diabetes Complication Severity Index
      showed poorer performance compared to the DNN model. CONCLUSIONS: Our results
      indicated that the DNN model is an appropriate tool to predict CRC risk in
      patients with T2DM in Taiwan.

PMID- 30213136
TI  - Voltage-Dependent Calcium Channels, Calcium Binding Proteins, and Their
      Interaction in the Pathological Process of Epilepsy.
AB  - As an important second messenger, the calcium ion (Ca2+) plays a vital role in
      normal brain function and in the pathophysiological process of different
      neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's
      disease (PD), and epilepsy. Ca2+ takes part in the regulation of neuronal
      excitability, and the imbalance of intracellular Ca2+ is a trigger factor for the
      occurrence of epilepsy. Several anti-epileptic drugs target voltage-dependent
      calcium channels (VDCCs). Intracellular Ca2+ levels are mainly controlled by
      VDCCs located in the plasma membrane, the calcium-binding proteins (CBPs) inside
      the cytoplasm, calcium channels located on the intracellular calcium store
      (particular the endoplasmic reticulum/sarcoplasmic reticulum), and the Ca2+-pumps
      located in the plasma membrane and intracellular calcium store. So far, while
      many studies have established the relationship between calcium control factors
      and epilepsy, the mechanism of various Ca2+ regulatory factors in epileptogenesis
      is still unknown. In this paper, we reviewed the function, distribution, and
      alteration of VDCCs and CBPs in the central nervous system in the pathological
      process of epilepsy. The interaction of VDCCs with CBPs in the pathological
      process of epilepsy was also summarized. We hope this review can provide some
      clues for better understanding the mechanism of epileptogenesis, and for the
      development of new anti-epileptic drugs targeting on VDCCs and CBPs.

PMID- 30213142
TI  - Comparative Study of Water-Leaching and Acid-Leaching Pretreatment on the Thermal
      Stability and Reactivity of Biomass Silica for Viability as a Pozzolanic Additive
      in Cement.
AB  - The present work aims to introduce a novel and eco-friendly method, i.e., a water
      leaching pretreatment for extracting highly reactive biomass silica from rice
      husk (RH), for viability as a pozzolanic additive in cement. For comparison, the
      traditional acid pretreatment method was also employed throughout the
      experimental study. The silica from RH was extracted using boiled deionized water
      and acid solution as leaching agents to remove the alkali metal impurities, and
      then dried and submitted to pyrolysis treatment. The results indicated that
      potassium was found to be the major contaminant metal inducing the formation of
      undesirable black carbon particles and the decrease in crystallization
      temperature of amorphous RHA silica. The boiling-water-leaching pretreatment and
      acid-leaching pretreatment on RHs significantly removed the metallic impurities
      and reduced the crystallization sensitivity of RHA silica to calcination
      temperature. A highly reactive amorphous silica with purity of 96% was obtained
      from RH via 1 N hydrochloric acid leaching followed by controlled calcination at
      600  degrees C for 2 h. The acid treatments increased the crystallization
      temperature of silica to 1200  degrees C and retained the amorphous state of
      silica for 2.5 h. In the case of water-leaching pretreatment, leaching duration
      for 2.5 h could yield an amorphous silica with purity of 94% and render the
      silica amorphous at 900  degrees C for 7 h. The RHA silica yielded by water
      leaching pretreatment presented a comparable enhancing effect to that of acid
      leaching on hydration and improved the strength of cement. Furthermore, compared
      with the acid-leaching method, the water-leaching pretreatment method is more
      environmentally friendly and easier to operate, and hence more widely available.

PMID- 30213144
TI  - Classification of Tidal Breathing Airflow Profiles Using Statistical Hierarchal
      Cluster Analysis in Idiopathic Pulmonary Fibrosis.
AB  - In idiopathic pulmonary fibrosis (IPF) breathing pattern changes with disease
      progress. This study aims to determine if unsupervised hierarchal cluster
      analysis (HCA) can be used to define airflow profile differences in people with
      and without IPF. This was tested using 31 patients with IPF and 17 matched
      healthy controls, all of whom had their lung function assessed using spirometry
      and carbon monoxide CO transfer. A resting tidal breathing (RTB) trace of two
      minutes duration was collected at the same time. A Euclidian distance technique
      was used to perform HCA on the airflow data. Four distinct clusters were found,
      with the majority (18 of 21, 86%) of the severest IPF participants (Stage 2 and
      3) being in two clusters. The participants in these clusters exhibited a distinct
      minute ventilation (p < 0.05), compared to the other two clusters. The
      respiratory drive was greatest in Cluster 1, which contained many of the IPF
      participants. Unstructured HCA was successful in recognising different airflow
      profiles, clustering according to differences in flow rather than time. HCA
      showed that there is an overlap in tidal airflow profiles between healthy RTB and
      those with IPF. The further application of HCA in recognising other respiratory
      disease is discussed.

PMID- 30213143
TI  - Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview.
AB  - Poloxamer 407, also known by the trademark Pluronic(r) F127, is a water-soluble,
      non-ionic triblock copolymer that is made up of a hydrophobic residue of
      polyoxypropylene (POP) between the two hydrophilic units of polyoxyethylene
      (POE). Poloxamer 407-based hydrogels exhibit an interesting reversible thermal
      characteristic. That is, they are liquid at room temperature, but they assume a
      gel form when administered at body temperature, which makes them attractive
      candidates as pharmaceutical drug carriers. These systems have been widely
      investigated in the development of mucoadhesive formulations because they do not
      irritate the mucosal membranes. Based on these mucoadhesive properties, a simple
      administration into a specific compartment should maintain the required drug
      concentration in situ for a prolonged period of time, decreasing the necessary
      dosages and side effects. Their main limitations are their modest mechanical
      strength and, notwithstanding their bioadhesive properties, their tendency to
      succumb to rapid elimination in physiological media. Various technological
      approaches have been investigated in the attempt to modulate these properties.
      This review focuses on the application of poloxamer 407-based hydrogels for
      mucosal drug delivery with particular attention being paid to the latest
      published works.

PMID- 30213148
TI  - Tracheation of abdominal ganglia and cerci in the house cricket Acheta domesticus
      (Orthoptera, Gryllidae).
AB  - Patterns of tracheation in the abdominal central nervous system and the cerci of
      Acheta domesticus are described from whole mounts, and light and electron
      microscopy. The tracheal supply of the ganglia is derived from ventral
      longitudinal tracheal trunks which have segmental connections to the spiracels.
      Each abdominal ganglion is served by a single pair of tracheal trunks, except the
      terminal ganglion, which has two pairs. Within the ganglia, tracheoles occur
      principally in association with glia-rich areas of the neuropile. We suggest that
      the respiratory exchange may be concentrated in the cell bodies of neurons and
      glia. Each cercus has a tracheal supply in paralle with a large air sac which, it
      is suggested, serves to lighten the cercus, functions as a resonator for sound
      reception, or facilitates tidal flow of hemolymph and postecdysial expansion of
      the cercus. No tracheae run continuously between ganglia or between the terminal
      ganglion and the cerci, and they do not appear to have a potential role as a
      contact guidance pathway for cercal nerve growth.

PMID- 30213145
TI  - Characterization of the Microbial Population Inhabiting a Solar Saltern Pond of
      the Odiel Marshlands (SW Spain).
AB  - The solar salterns located in the Odiel marshlands, in southwest Spain, are an
      excellent example of a hypersaline environment inhabited by microbial populations
      specialized in thriving under conditions of high salinity, which remains poorly
      explored. Traditional culture-dependent taxonomic studies have usually under
      estimated the biodiversity in saline environments due to the difficulties that
      many of these species have to grow at laboratory conditions. Here we compare two
      molecular methods to profile the microbial population present in the Odiel
      saltern hypersaline water ponds (33% salinity). On the one hand, the construction
      and characterization of two clone PCR amplified-16S rRNA libraries, and on the
      other, a high throughput 16S rRNA sequencing approach based on the Illumina MiSeq
      platform. The results reveal that both methods are comparable for the estimation
      of major genera, although massive sequencing provides more information about the
      less abundant ones. The obtained data indicate that Salinibacter ruber is the
      most abundant genus, followed by the archaea genera, Halorubrum and
      Haloquadratum. However, more than 100 additional species can be detected by Next
      Generation Sequencing (NGS). In addition, a preliminary study to test the
      biotechnological applications of this microbial population, based on its ability
      to produce and excrete haloenzymes, is shown.

PMID- 30213149
TI  - Ultrastructural features of the retina and optic nerve of Strombus luhuanus, a
      marine gastropod.
AB  - The retina and optic nerve of Strombus luhuanus were examined by transmission
      electron microscopy in order to provide an ultrastructural basis for their
      electrophysiological responses, described elsewhere. The retina exhibits a
      distinct rhabdomeric layer and layers of cell nuclei and neuropile. These layers
      are comprised predominantly of three cell types that can be readily distinguished
      on the basis of their shape, their nuclei and cytoplasmic inclusions such as
      vesicles and filaments. One type of cell, apparently a photoreceptor that
      depolarizes in response to photic stimulation, possesses a long distal segment
      with microvilli; such distal segments comprise the bulk of the rhabdomeric layer.
      A second cell type, which appears to be supportive in function, contains a bundle
      of tightly packed tonofilaments that extend across the retina from the capsule to
      the vitreous body; this cell is quite narrow except in the region near the
      rhabdomeric layer, where it is expanded and wraps around the other cell types. A
      third type of cell possesses many short microvilli that project from its apical
      end into the rhabdomeric layer; it may be a second type of photoreceptor or
      another type of neuron. The retina also contains bundles of cilia that appear to
      project from a possible fourth type of cell. The layer of neuropile contains
      numerous processes that exhibit a variety of vesicle types and structures
      generally associated with synapses; these appear to play a role in mediating
      inhibitory and excitatory interactions between the retinal neurons. The optic
      nerve exhibits two populations of fiber distinguishable on the basis of mean
      diameter. Fibers in these two populations apparently yield "on" and "off"
      discharges in response to photic stimulation of the eye.

PMID- 30213146
TI  - Effects of 462 nm Light-Emitting Diode on the Inactivation of Escherichia coli
      and a Multidrug-Resistant by Tetracycline Photoreaction.
AB  - The adaptability of bacterial resistance to antibiotics contributes to its high
      efficiency during evolution. Tetracycline (TC) is a broad-spectrum antimicrobial
      agent. Chromatographic analyses and mass spectrometry were used to study the
      effects of the light illumination of a 462 nm light-emitting diode (LED) on the
      conformational changes of TC in a phosphate buffer solution (PBS, pH 7.8).
      Especially, the inactivation of superoxide anion radicals (O2*-) and Escherichia
      coli (E. coli), including that of a multidrug-resistant E. coli (MDR E. coli),
      were investigated during the photolysis of TC. A photolysis product of TC (PPT)
      was generated in an alkaline solution after the illumination of a blue light. The
      mass spectra of PPT had characteristic ion signals in m/z 459, 445, and 249.1 Da.
      The PPT has the molecular formula of C22H22N2O9, and the exact mass is 458.44
      g/mol. The inactivation of MDR E. coli is not significant with TC treatment. The
      drug-resistant ability of MDR E. coli has a less significant effect on PPT, and
      the changed conformation of TC retained the inactivation ability of MDR E. coli
      upon blue light photoreaction. With TC, illuminated by a blue light in a pH 7.8
      PBS, O2*- was generated from TC photolysis, which enhanced the inactivation of E.
      coli and MDR E. coli. A 96.6% inactivation rate of MDR E. coli was reached with
      TC under 2.0 mW/cm2 blue light illumination at 25 +/- 3  degrees C for 120 min,
      and the effects of the TC-treated photoreaction on MDR E. coli viability
      repressed the growth of MDR E. coli by 4 to 5 logs. The present study of the blue
      light photoreaction of TC offers a new approach to the inactivation of MDR E.
      coli.

PMID- 30213147
TI  - Functional Evolution of Avian RIG-I-Like Receptors.
AB  - RIG-I-like receptors (retinoic acid-inducible gene-I-like receptors, or RLRs) are
      family of pattern-recognition receptors for RNA viruses, consisting of three
      members: retinoic acid-inducible gene I (RIG-I), melanoma differentiation
      associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2). To
      understand the role of RLRs in bird evolution, we performed molecular
      evolutionary analyses on the coding genes of avian RLRs using filtered predicted
      coding sequences from 62 bird species. Among the three RLRs, conservation score
      and dN/dS (ratio of nonsynonymous substitution rate over synonymous substitution
      rate) analyses indicate that avian MDA5 has the highest conservation level in the
      helicase domain but a lower level in the caspase recruitment domains (CARDs)
      region, which differs from mammals; LGP2, as a whole gene, has a lower
      conservation level than RIG-I or MDA5. We found evidence of positive selection
      across all bird lineages in RIG-I and MDA5 but only on the stem lineage of
      Galliformes in LGP2, which could be related to the loss of RIG-I in Galliformes.
      Analyses also suggest that selection relaxation may have occurred in LGP2 during
      the middle of bird evolution and the CARDs region of MDA5 contains many
      positively selected sites, which might explain its conservation level. Spearman's
      correlation test indicates that species-to-ancestor dN/dS of RIG-I shows a
      negative correlation with endogenous retroviral abundance in bird genomes,
      suggesting the possibility of interaction between immunity and endogenous
      retroviruses during bird evolution.

PMID- 30213150
TI  - Ultrastructural investigation of spermiogenesis in Peripatopsis capensis
      (Onychophora).
AB  - Early spermatids of the onychophoran Peripatopsis capensis are spherical cells
      with a centrally located nucleus, numerous mitochondria, Golgi complexes,
      microtubules and two centrioles. During spermiogenesis, Golgi vesicles migrate to
      one side of the cell where they form a tight aggregate, which is later shed. The
      mature spermatozoon has no acrosome. Several mitochondria fuse to form a middle
      piece containing three large mitochondria. Nucleus and middle-piece elongate,
      presumably under the influence of helically twisted microtubules. Outside this
      set of microtubules a continuous layer of endoplasmic reticulum cisternae is
      formed which separates the interior portion of the cell from an external
      cytoplasmic rim, which is later shed. Outside the 9 + 2 complex, the tail
      presents nine accessory microtubules, and a peripheral layer of microtubules
      beneath the plasma membrane. The enforcement of the tail structure may be related
      to the fertilization biology of this animal, which is by "hypodermal"
      impregnation.

PMID- 30213151
TI  - Ultrastructure of the bone marrow of the salamander Plethodon glutinosus
      (Caudata: Plethodontidae).
AB  - The unusual lymphogranulopoietic bone marrow of the large lungless salamander
      Plethodon glutinosus was examined by light and electron microscopy. Developing
      neutrophils, eosinophils, and fat cells were found in large numbers, while
      lymphocytes of various sizes, plasma cells, plasmablasts, macrophages, pigment
      cells, and fibroblasts were present in more moderate numbers. Basophils were
      observed only rarely. Macrophages were found in extravascular locations and did
      not appear to be associated directly with the walls of the blood vessels
      supplying the marrow. Both neutrophils and eosinophils seemed to arise from small
      precursor cells whose ultrastructural features bore a resemblance in some ways to
      those of mammalian myeloblasts described by Bainton and Farquhar ('66).
      Developing neutrophils and eosinophils seemed to produce only single populations
      of specific cytoplasmic granules, rather than both primary (azurophilic) and
      secondary (specific) inclusions, as are produced typically by mammalian
      granulocytes. Both eosinophilic and neutrophilic granules were formed in
      association with Golgi complexes; and eosinophilic granules were much larger,
      more densely stained, and more regularly rounded in shape than the inclusions of
      developing neutrophils. Peroxidase activity was associated with the specific
      granules of neutrophils but seemed to be lacking in the granules of eosinophils.
      The specific granules of eosinophils were especially unusual because they
      contained irregularly shaped, lightly stained cores which occasionally displayed
      a distinctly crystalline substructural organization. The specific granules of
      basophils also possessed a prominent crystalline organization. The overall
      appearance of the marrow of Plethodon suggests that it functions not only as a
      valuable source of neutrophils, eosinophils, and cells of the lymphoid series,
      but also as a part of the phagocytic system of the animals and as an important
      repository for fat.

PMID- 30213152
TI  - Ultrastructure of an exocrine dermal gland in the gills of the grass shrimp,
      Palaemonetes pugio: Occurrence of transitory ciliary axonemes associated with the
      sloughing and reformation of the ductule.
AB  - Exocrine dermal glands, comparable to the class 3 glandular units of insects, are
      found in the gills of the grass shrimp, Palaemonetes pugio. The dermal glands are
      composed of three cells: secretory cell, hillock cell and canal cell. Originating
      as a complex invagination of the apical cytoplasm of the granular secretory cell,
      a duct ascends through the hillock and canal cells to the cuticular surface. The
      duct is divisible into four regions: the secretory apparatus in the granular
      secretory cell, the locular complex, the hillock region within the hillock cell
      and the canal within the canal cell. A tubular ductule is contained within the
      latter two regions. As the ductule ascends to the cuticular surface, its
      constitution gradually changes from one of a fibrous material to one which
      possesses layers of epicuticle. During the proecdysial period, the ductule is
      extruded into the ecdysial space and this is followed by the secretion of a new
      ductule. Temporary ciliary structures, located near the secretory apparatus of
      the secretory cell, are associated with the extrusion and reformation of the
      ductule. Characterized only by a basal body and rootlets throughout most of the
      intermolt cycle, the ciliary organelles give rise to temporary axonemic processes
      which ascend through the ductule toward the ecdysial space at the onset of
      proecdysis. Subsequently, the old ductule is sloughed off and a new ductule is
      reformed around the ciliary axonemes. Following this reformation, the ciliary
      axonemes degenerate. The function of cytoplasmic processes, derived from the
      apical cytoplasm of the secretory cell, is also discussed.

PMID- 30213153
TI  - Ultrastructure of the accessory glands of the Mediterranean flour moth.
AB  - Five regions are recognized in the accessory glands of the Mediterranean flour
      moth, Anagasta kuehniella (Zeller), on the basis of cellular morphology and
      aggregates of secretory material in the lumen. Some variation is found in each of
      the posterior four regions, especially the third one. In the most anterior region
      (region 1) the epithelium is composed of a single type of cell, while in each of
      the other regions there are two classes of cells. The cells of region 1 and one
      class in each of the other four regions are fairly typical exocrine cells with
      extensive rough endoplasmic reticula. Secretion is primarily via Golgi-derived
      vesicles. Apocrine secretion in the form of sloughing off of the apical cytoplasm
      probably also occurs in all regions but is most prominent in the posterior two
      regions. One class of cells is very similar in morphology in each of the
      posterior four regions though their secretory products form characteristic
      aggregates in the lumen. The second class of cells (foliate cells) occurring in
      the posterior four segments is most notably characterized by elongate apical
      projections that extend out into the lumen. The apical projections contain large
      quantities of glycogen, some microtubules, and, in some cases, many minute
      mitochondria. The membrane content of the projections is also very high. In the
      anterior regions, the membranes are mostly fused in pairs and typically form
      multilayered whorls. Fusion and whorl formation decrease in the posterior
      regions. The cytoplasm of the foliate cells has a high organelle content
      including many lysosomes and mitochondria. The latter exhibit considerable
      polymorphism, with particular forms occurring in the different regions of the
      glands. The apical projections of the foliate cells are detached during
      copulation, presumably as the result of nervous stimulation, and become a part of
      the ejaculate. Replenishment of all secretory material, including the apical
      projections, occurs after copulation.

PMID- 30213154
TI  - Ultrastructure of the parathyroid gland of the japanese lizard in the spring and
      summer season.
AB  - The ultrastructure of the parathyroid glands of adult Japanese lizards
      (Takydromus tachydromoides) in the spring and summer season was examined. The
      parenchyma of the gland consists of chief cells arranged in cords or solid
      masses. Many chief cells contain numerous free ribosomes and mitochondria, well
      developed Golgi complexes, a few lysosome-like bodies, some multivesicular bodies
      and relatively numerous lipid droplets. The endoplasmic reticulum is mainly
      smooth-surfaced. Cisternae of the rough endoplasmic reticulum are distributed
      randomly in the cytoplasm. Small coated vesicles of 700-800 A in diameter are
      found occasionally in the cytoplasm, especially in the Golgi region. The chief
      cells contain occasional secretory granules of 150-300 nm in diameter that are
      distributed randomly in the cytoplasm and lie close to the plasma membrane.
      Electron dense material similar to the contents of the secretory granules is
      observed in the enlarged intercellular space. These findings suggest that the
      secretory granules may be discharged into the intercellular space by an
      eruptocrine type of secretion. Coated vesicles (invaginations) connected to the
      plasma membrane and smooth vesicles arranged in a row near the plasma membrane
      are observed. It is suggested that such coated vesicles may take up extracellular
      proteins. The accumulation of microfilaments is sometimes recognized.
      Morphological evidence of synthetic and secretory activities in the chief cells
      suggests active parathyroid function in the Japanese lizard during the spring and
      summer season.

PMID- 30213155
TI  - Tooth crown morphology in caecilians (Amphibia: Gymnophiona).
AB  - The morphology of tooth crowns is variable inter-specifically among caecilians.
      Cusp number and shape, crown dimensions, and crown curvature characterize various
      species and have both functional and phylogenetic implications. Ichthyophis,
      Uraeotyphlus, Hypogeophis, and Geotrypetes have bicuspid teeth; Dermophis,
      Gymnopis, Caecilia, and Typhlonectes monocuspid. Crown morphology as revealed by
      scanning electron microscopy is associated with prey grasping and, in one case,
      possible specialization of prey type.

PMID- 30213156
TI  - The wrist joint of two-toed sloths and its relevance to brachiating adaptations
      in the hominoidea.
AB  - Two-toed sloths have evolved a wrist complex that includes the following traits:
      (1) diminution and distal migration of the pisiform, with a loss of contact with
      the ulna; (2) reduction of the distal end of the ulna to a styloid process; and
      (3) extremely reduced contact between the ulna and triquetrum. These traits were
      proposed by Lewis ('65, '74) to be indicative of brachiating habits and to be a
      unique adaptation of the Hominoidea. Cartmill and Milton ('77) recently found a
      similar complex in the wrists of the lorisines. Very similar adaptations of the
      wrist among the Hominoidea, lorisines, and two-toed sloths clearly refute
      contentions of Lewis and strengthen the hypothesis of Cartmill and Milton that
      the traits common to those animals are due to similar slow, cautious, but
      acrobatic locomotion.

PMID- 30213157
TI  - Ultrastructure of differentiated malpighian tubules from cockroach nymphs during
      the molting cycle.
AB  - Differentiated Malpighian tubules of Periplaneta americana nymphs consist of four
      distinct regions. The distal, middle, and proximal regions are similar to the
      same regions in adult tubules. However, the transparent portion of the middle
      region was found to have ultrastructural characteristics different from those of
      the longer opaque segment of the middle region and the two other tubule regions.
      This newly distinguished region is called the lower middle region. Transitional
      zones, areas where cells show characteristics of two adjacent regions, are
      apparent between the distal and middle regions and between the middle and lower
      middle regions. The middle region of primary tubules undergoes an increase in
      autophagic activity and a modification of its basal infoldings and microvilli
      shortly before each molt. An increase in autophagic activity is also observed in
      the lower middle region near the time of molting.

PMID- 30213158
TI  - Application of contrast-enhanced ultrasound for evaluation of thyroid nodules.
AB  - Contrast-enhanced ultrasound (CEUS) is widely used to evaluate tumor
      microcirculation, which is useful in the differential diagnosis between benignity
      and malignancy. In the last 10 years, the applicability of CEUS to thyroid
      nodules has greatly improved due to technological refinements and the development
      of second-generation contrast agents. In this review, we summarize the
      applications of CEUS for thyroid nodules, focusing on the imaging findings of
      malignant and benign nodules in the existing literature and the use of those
      findings to predict malignancies, with an additional brief description of the
      utilization of CEUS for other thyroid-related diseases.

PMID- 30213159
TI  - Sensory and Motor Behavior Evidences Supporting the Usefulness of Conditioned
      Medium from Dental Pulp-Derived Stem Cells in Spinal Cord Injury in Rats.
AB  - STUDY DESIGN: Experimental animal study. PURPOSE: This study aimed to assess
      effects of conditioned medium (CM) of dental pulp-derived stem cells loaded in
      collagen hydrogel on functional recovery following spinal cord injury (SCI).
      OVERVIEW OF LITERATURE: SCI affects sensory and motor functions, and behavioral
      recovery is the most essential purpose of therapeutic intervention. Recent
      studies have reported that CM from dental pulp-derived stem cells has therapeutic
      benefits. In addition, collagen hydrogel acts as a drug delivery system in SCI
      experiments. METHODS: Stem cells from human exfoliated deciduous teeth (SHEDs)
      were cultured, and SHED-CM was harvested and concentrated. Collagen hydrogel
      containing SHED-CM was prepared. The rats were divided into five groups receiving
      laminectomy, compressive SCI with or without intraspinal injection of
      biomaterials (SHED-CM), and collagen hydrogel with or without SHED-CM. Basso,
      Beattie, and Bresnahan (BBB) scoring, inclined plane, cold allodynia, and beam
      walk tests were performed for 6 weeks to assess locomotor, motor, sensory, and
      sensory-motor performances, respectively. RESULTS: Scores of the rats receiving
      SHED-CM loaded in collagen hydrogel were significantly better than those of the
      other injured groups at 1-week post-injury for BBB, 2 weeks for inclined plane, 2
      weeks for cold allodynia, and 4 weeks for beam walk tests (p <0.05). The
      differences remained significant throughout the study. CONCLUSIONS: Intraspinal
      administration of SHED-CM loaded in collagen hydrogel leads to improved
      functional recovery and proposes a cell-free therapeutic approach for SCI.

PMID- 30213160
TI  - Magnetically Controlled Growing Rods: The Experience of Mechanical Failure from a
      Single Center Consecutive Series of 28 Children with a Minimum Follow-up of 2
      Years.
AB  - STUDY DESIGN: Retrospective observational study of a continuous series of 28
      children. PURPOSE: To determine the mechanical failure rate in our cohort of
      children treated with magnetically controlled growth rods (MCGRs). OVERVIEW OF
      LITERATURE: Previous studies report a MCGR mechanical failure rate of 0%-75%.
      METHODS: All patients with MCGR implantation between 2012 and 2015 were examined
      and followed up for a minimum of 2 years. A retrospective evaluation of
      contemporaneously documented clinical findings was conducted, and radiographs
      were retrospectively examined for mechanical failure. The external remote
      controller (ERC)-specified length achieved in the clinic was compared to the
      length measured on subsequent radiographs. RESULTS: Fourteen mechanical failures
      were identified in 28 children (50%) across a total of 52 rods (24 pairs and four
      single constructs). Mechanical failures were due to: failure to lengthen under
      general anesthesia (seven children), actuator pin fracture (four), rod fracture
      (one), foundation screw failure (one), and ran out of rod length (one). Of the 14
      mechanical failures, six were treated with final fusion operations (reflecting
      limited further growth potential), and eight patients were treated with the
      intention for further lengthening. We therefore consider these eight patients to
      represent the true incidence of mechanical failure in our cohort (29%). The
      difference between the ERC length and radiographic length was found to be
      identical in 11% cases; 35% were overestimates, and 54% were underestimates. The
      median underestimate was 2.45 mm whereas the median overestimate was 3.1 mm per
      distraction episode. In total, 95% of all ERC distractions were within +/-10 mm
      of the radiographic length achieved over a median of nine distraction episodes.
      CONCLUSIONS: Our series is the most comprehensive MCGR series published to date,
      and we present a mechanical failure rate of 29%. Clinicians should be mindful of
      the discrepancies between ERC length and radiographic measurements of rod length;
      other modalities may be more helpful in this regard.

PMID- 30213161
TI  - Endoscopic Decompression Can Be Effective for Diagnosing and Treating Tubercular
      Spondylodiskitis with Early Epidural Spinal Compression: A Retrospective Study of
      18 Cases.
AB  - STUDY DESIGN: Retrospective study. PURPOSE: In this study, we describe an
      endoscopic method of effectively treating tubercular lumbar spondylodiskitis with
      early onset epidural spinal cord compression in the lumbar spine on magnetic
      resonance imaging (MRI). OVERVIEW OF LITERATURE: Percutaneous aspiration and
      biopsy of spondylodiskitis under ultrasonography and computer tomography scan
      invariably provides an inadequate diagnosis. METHODS: From May 2015 to May 2017,
      18 patients presented with intractable back pain and were diagnosed with
      tubercular spondylodiskitis on MRI; these patients were enrolled in this study.
      The goal was to confirm the pathogen on biopsy, drain the abscess, and perform
      debridement. Chemotherapy was started after histologic diagnosis, and data
      collected included blood cell counts, erythrocyte sedimentation rate, C-reactive
      protein, and repeat MRI after 3 months. RESULTS: Mean duration of surgery was 52
      minutes. Mean follow-up was 17 months. The average preoperative Visual Analog
      Scale score of 8 (range, 6-10) decreased to 3 (range, 1-8) postoperatively.
      Tubercular spondylodiskitis was observed in 14 cases; two cases were pyogenic,
      and the biopsy was inconclusive in two cases. After adequate chemotherapy, no
      recurrences were noted. CONCLUSIONS: We hereby conclude that endoscopic biopsy
      and drainage can provide a better diagnosis and decrease pain in a predictable
      manner.

PMID- 30213162
TI  - Short-Term Clinical Evaluation of Enhanced Unilateral Open-Door Laminoplasty
      Using Titanium Mesh.
AB  - STUDY DESIGN: Observational, cross-sectional study. PURPOSE: The purpose of this
      study was to evaluate the clinical efficacy and safety profile of open-door
      laminoplasty (ODL) using titanium mesh. OVERVIEW OF LITERATURE: The most
      appropriate surgical management of degenerative spine disorders, particularly
      ossification of the posterior longitudinal ligament, remains controversial and
      continues unabated in the neurosurgical community. However, recently, ODL has
      become popular among surgeons. Many modifications have been developed since
      Hirabayashi in 1983 to enhance the clinical efficacy and safety of this
      procedure. METHODS: We reviewed the obtained data of patients with ossification
      of the posterior longitudinal ligament (OPLL) who underwent ODL using titanium
      mesh at Neurosurgery Subdivision, the Dr. Sardjito Hospital, Yogyakarta,
      Indonesia, during January 2013-December 2015. Motor improvement (Nurick score),
      axial neck pain (neck disability index [NDI]), and incidence of complications
      were pre- and postoperatively examined, and the clinical efficacy and safety of
      the procedure was evaluated. Data were analyzed using Wilcoxon signed-rank test
      and paired t -test. RESULTS: This study included five patients were included
      (i.e., four males and one female) with mean age of 47.00+/-9.68 years, where
      reassessments were done after mean follow up of 20.2+/-4.74 months. Mean duration
      of surgery was 165+/-12.55 minutes. Pre- and postoperative motor assessments were
      3.4+/-1.52 and 2.0+/-1.22 (p =0.059), respectively. Axial neck pains using NDI
      were 23.60+/-7.44 and 12.40+/-6.50 (p =0.004) before and after operations,
      respectively. No infected postoperative scar was found, and only one patient had
      a left C5 motor palsy. CONCLUSIONS: The results of the present study suggest that
      enhanced ODL using titanium mesh has favorable outcome and safety profile, which
      can pave the way for a suitable treatment in patients with OPLL.

PMID- 30213163
TI  - Validity and Reliability of the Arabic Version of the Copenhagen Neck Functional
      Disability Scale in Neck Pain Patients.
AB  - STUDY DESIGN: Prospective observational study. PURPOSE: To test the face
      validity, content validity, feasibility, internal consistency, reliability, and
      test-retest reliability of the Arabic version of the Copenhagen Neck Functional
      Disability Scale (CNFDS). OVERVIEW OF LITERATURE: CNFDS is a clinical evaluation
      tool that accurately reflects the patient's perception regarding his/her
      functionality with existing cervical pain. This study aimed to investigate the
      validity and reliability of the Arabic version of the CNFDS in measuring the
      disability level in chronic neck pain patients. METHODS: Seventy-four patients
      with neck pain were recruited, and 135 sheets (test and retest sheets) were
      completed by patients; two expert panels (each comprising ten experts)
      participated in this study. Arabic translation (forward translation), development
      of the preliminary translated version, English translation (backward
      translation), development of the prefinal version, and testing of the prefinal
      version was performed by experts; thereafter, the final version was tested on
      patients. Index of clarity, expert proportion of clearance, index of content
      validity (CVI), expert proportion of relevance, descriptive statistics, missed
      item index, Cronbach's alpha, and Spearman's rank correlation coefficient were
      used for statistical analyses. RESULTS: The study revealed that the scale index
      of clarity was 86.84%, scale CVI was 99.33%, scale-level content validity index
      (universal agreement method) was 99.33%, 99.15% of the scale items were filled in
      all sheets, the scale was answered in less than 3 minutes in about 75% cases,
      Cronbach's alpha was 0.856 (0.796, 0.905), and all Spearman's correlations
      between the test and retest results were statistically significant. CONCLUSIONS:
      The Arabic version of the CNFDS has adequate validity and reliability for the
      measurement of the disability level in chronic neck pain patients.

PMID- 30213164
TI  - Anterolateral Cervical Kyphoplasty for Metastatic Cervical Spine Lesions.
AB  - STUDY DESIGN: Retrospective case series. PURPOSE: To evaluate the clinical and
      radiological efficacy of anterolateral kyphoplasty for cervical spinal
      metastasis. OVERVIEW OF LITERATURE: Although the spine is the third most common
      site of tumor metastasis, the cervical spine is the least commonly affected
      (incidence, 10%-15%). Surgical decompression is highly challenging because of the
      proximity of neural and vascular elements. Kyphoplasty for cervical spine
      metastasis has been described in small case reports with promising results.
      METHODS: Retrospective analysis of a prospective collected single-center spine
      metastasis database was done for cervical kyphoplasty cases. Data pertaining to
      age, sex, primary tumor diagnosis, modified Tokuhashi score, Spinal Instability
      Neoplastic Score (SINS), preoperative Visual Analog Scale (VAS) score, and
      analgesic medication were extracted. Postoperative data included VAS score at
      postoperative day 1, duration of hospitalization, self-reported functional
      outcome, and VAS score at the last follow-up. RESULTS: Eleven patients (mean age,
      62.5 years) with cervical spine metastases were treated with 15-level
      kyphoplasty. Mean Tokuhashi score was 8.1, and mean SINS was 7.85. Mean
      preoperative pain score was 7.1, and 82% of patients used opioid analgesics. Mean
      total bleeding volume was 100 mL. Mean complication-free length of stay was 2.6
      days with a decrease in postoperative pain (VAS score=2.8, p <0.05). There was a
      56% decrease in opioid dosage and the number of consumed analgesics (1.09, p
      =0.004). Eightytwo percent of the patients reported excellent improvement at the
      last follow-up self-assessment. CONCLUSIONS: To our knowledge, this case series
      represents the largest series of vertebral augmentation using balloon kyphoplasty
      for cervical spinal metastasis. This technique is associated with low
      postoperative complications as well as significant decrease in pain, use of
      opioids, and length of hospital stay. The main indications for vertebral
      kyphoplasty are lytic lesions of the cervical spine, painful lesions refractory
      to medical treatment, SINS score of 6-10, and absence of posterior wall defect.

PMID- 30213165
TI  - Risk Factors for Pseudarthrosis in Minimally-Invasive Transforaminal Lumbar
      Interbody Fusion.
AB  - STUDY DESIGN: Retrospective cohort study (level of evidence: 4). PURPOSE: To
      describe the potential comorbid, operative, and radiographic risk factors for the
      development of clinically-relevant pseudarthrosis following minimally-invasive
      transforaminal lumbar interbody fusion (MIS-TLIF). OVERVIEW OF LITERATURE: MIS
      TLIF has shown long-term clinical outcomes with decreased perioperative morbidity
      and earlier return to work, similar to those of open TLIF. However, unsuccessful
      fusion still remains a concern. The impacts of various patient, operative, and
      radiographic risk factors have not been evaluated for their potential association
      with pseudarthrosis related to MIS-TLIF. METHODS: Between 2012 and 2015, 204
      consecutive patients underwent one or two-level MIS-TLIF at St. Joseph's
      University Medical Center, Paterson, NJ, USA; they had a minimum of 1 year of
      follow-up. The patients were divided into two cohorts: those who developed
      clinically-relevant pseudarthrosis and those who did not. Clinically-relevant
      pseudarthrosis was determined by both evidence on computed tomography and
      presence of continued clinical symptoms at 1-year follow-up. RESULTS: Revision
      surgery was the only identified non-radiographic factor associated with
      pseudarthrosis. Disc angle had the highest (R 2=0.8), followed by anterior disc
      height (R 2=0.79). Although posterior disc height and the ratio of anterior to
      posterior disc height showed a marked relationship with the outcome, the R 2
      values were <0.3, thus indicating a less-strong correlation. The overall
      pseudarthrosis rate was 8%. No statistically significant differences were
      identified between the two cohorts with respect to mean age, sex, medical
      comorbidities, smoking status, or number of levels fused. CONCLUSIONS: Clinically
      relevant pseudarthrosis is not uncommon following MIS-TLIF. In the current study,
      undergoing revision surgery, disc angle, and anterior disc height were observed
      to be associated with clinically-relevant pseudarthrosis. This study demonstrated
      that the patient population may benefit from an alternate approach.

PMID- 30213166
TI  - Use of Bioelectrical Impedance Analysis for the Measurement of Appendicular
      Skeletal Muscle Mass/Whole Fat Mass and Its Relevance in Assessing Osteoporosis
      among Patients with Low Back Pain: A Comparative Analysis Using Dual X-ray
      Absorptiometry.
AB  - STUDY DESIGN: Cross-sectional observational study. PURPOSE: To compare
      measurements of appendicular skeletal muscle mass (ASMM) and whole fat mass (WFM)
      obtained using dualenergy X-ray absorptiometry (DXA) and bioelectrical impedance
      analysis (BIA) among patients with low back pain (LBP). Moreover, the study
      investigated the correlation between BIA-based ASMM and DXA-based bone mineral
      density (BMD). Overview of the Literature: If reliable, BIA may be a useful
      alternative to DXA as a screening tool for sarcopenia and osteoporosis among
      patients with LBP. METHODS: Measurements were performed in 130 patients,
      including BMD of the lumbar spine and femoral neck. The correlation between DXA
      and BIA as well as between BIA-ASMM and BMD were evaluated. RESULTS: BIA and DXA
      were highly correlated in both male and female patients (r =0.73-0.90, p
      <0.0001). However, BIA consistently overestimated ASMM by 1.5-2.5 kg on an
      average (p <0.0001) and underestimated WFM (-4.0 to -2.7 kg) on an average (p
      <0.0001). BIA-based ASMM correlated with BMD of the lumbar spine in both male and
      female patients (r =0.28-0.37, p <=0.02) and that of the femoral neck (r =0.34
      0.51, p <=0.005). Regarding the calculated skeletal muscle index (SMI:
      ASMM/height [m2]) used as a criterion for sarcopenia, BIA-based SMI correlated
      with BMD of the lumbar spine in male patients (r =0.44, p =0.0004) and that of
      the femoral neck in female patients (r =0.33, p =0.009). CONCLUSIONS: BIA may be
      a favorable alternative to DXA as a screening tool for sarcopenia and
      osteoporosis among patients with LBP. Considering the overestimation of BIA-based
      ASMM and SMI, we recommend using the cutoff values for sarcopenia of 7.9 kg/m2
      for males and 6.1 kg/m2 for females.

PMID- 30213167
TI  - Outcomes and Prognosis of Neurological Decompression and Stabilization for Spinal
      Metastasis: Is Assessment with the Spinal Instability Neoplastic Score Useful for
      Predicting Surgical Results?
AB  - STUDY DESIGN: Retrospective study. PURPOSE: To evaluate the efficacy of the
      Spinal Instability Neoplastic Score (SINS) in predicting surgical outcomes and
      survival. Patients were categorized into two groups according to the SINS, and
      their surgical outcomes and survival following decompression and stabilization
      were assessed. OVERVIEW OF LITERATURE: Palliative surgery in patients with a life
      expectancy >=3 months may effectively improve their overall condition in the long
      term. Currently, the effectiveness of the SINS for predicting surgical results
      and survival remains controversial. METHODS: This study included 44 patients who
      underwent decompression and stabilization for spinal metastases at Yokosuka
      Kyosai Hospital between 2008 and 2017. The patients were divided into two groups:
      stable (SINS <=12) and unstable (SINS >=13). Changes in the Frankel score and
      Eastern Cooperative Oncology Group Performance Status (ECOG-PS) were compared
      between the two groups, and patient survival was evaluated according to the SINS,
      Tokuhashi score, and Katagiri score. RESULTS: The stable group (SINS range, 7-12)
      included 24 patients while the unstable group (SINS range, 13-16) included 20
      patients. The Frankel score significantly improved from 2.8 to 3.6 in the stable
      group (p <0.001) and from 2.7 to 3.9 in the unstable group (p <0.001). The ECOG
      PS significantly improved from 3.2 to 2.1 in the stable group (p <0.001) and from
      3.0 to 1.8 in the unstable group (p <0.001). There was a statistically
      significant difference in median survival between the two groups. CONCLUSIONS:
      All patients treated with palliative surgery showed favorable outcomes, as
      indicated by improved the Frankel score and ECOG-PS following surgery. However,
      median survival was significantly better in the stable group. The results of this
      study indicate that the SINS is appropriate for surgical decision making and may
      be used to predict survival.

PMID- 30213168
TI  - Impact of Multidisciplinary Spine Conferences on Surgical Planning and
      Perioperative Care in Elective Lumbar Spine Surgeries.
AB  - STUDY DESIGN: Pre- and post-implementation analysis. PURPOSE: We examined the
      impact of implementing multidisciplinary spine conferences-"spine board" reviews
      on the general utilization of elective lumbar spine surgeries in a tertiary
      medical institute. OVERVIEW OF LITERATURE: A multidisciplinary approach to spine
      care reportedly improves the appropriate utilization of surgical spine
      procedures. METHODS: A multidisciplinary spine board was established to review
      candidates selected for elective lumbar spine surgery. The board comprised
      representatives from orthopedic spine surgery, neurosurgery, psychology, physical
      therapy, radiology, pharmacy, primary care, pain management, anesthesiology, and
      veteran advocacy. Two similar 6-month periods were selected to study the impact
      of this implementation: pre-implementing (June 1, 2015 to November 30, 2015) and
      post-implementation (June 1, 2016 to November 30, 2016) periods. RESULTS: Between
      March 1, 2016 and December 30, 2016, the spine board discussed 11 patients. All
      patients underwent clinical examinations and radiological assessments findings
      that warranted elective lumbar surgery. The board recommended non-surgical
      interventions before proceeding with the planned surgeries in all cases. In the
      pre-implementation period, a total of 101 elective lumbar spine surgeries were
      performed. In the post-implementation period, a total of 51 elective lumbar spine
      surgeries were performed (p <0.05). The surgical plan for elective lumbar spine
      surgery in the post-implementation period was not directly influenced by the
      review of spine board because none of the cases were discussed in the
      conferences; however, the care occurred at a hospital where the spine board was
      implemented. There was no significant change in the number of cervical spine
      surgeries performed (66 preimplementation vs. 56 post-implementation). The
      average surgery duration was 52 minutes shorter in the post-implementation period
      compared with that in the pre-implementation period (p <0.05). CONCLUSIONS:
      Implementation of a multidisciplinary spine board was concurrent with an overall
      decrease in the utilization of lumbar spine surgeries for elective cases of low
      back pain in a tertiary medical center.

PMID- 30213169
TI  - Radiological and Clinical Outcomes of Balloon Kyphoplasty versus Radiofrequency
      Kyphoplasty in the Treatment of Vertebral Compression Fractures.
AB  - STUDY DESIGN: Retrospective cohort analysis. PURPOSE: Comparison of balloon
      kyphoplasty (BKP) and radiofrequency kyphoplasty (RFK) with respect to height
      restoration of the fractured vertebral bodies and the pain relief experienced
      after the surgical procedure. OVERVIEW OF LITERATURE: BKP and RFK both offer
      safe, time-saving, and potent treatment options for vertebral compression
      fractures, but neither of these methods demonstrated any key advantage over the
      other yet. METHODS: We performed a retrospective analysis of a cohort of 156
      patients (mean age, 73+/-11 years) with 252 fractured vertebral bodies treated
      with kyphoplasty. Pain intensity was measured using a Visual Analogue Scale.
      Preoperative and postoperative computed tomography images were analyzed and
      gauged using modified bisegmental Cobb angle, vertebral angle, as well as
      anterior (Ha), middle (Hm), and posterior (Hp) vertebral body heights. RESULTS:
      The mean postoperative pain relief was 5.1+/-1.8, which was maintained over the
      entire follow-up period. There were no significant differences in the pain relief
      between BKP and RFK. Postoperative changes in the vertebral angle (-1.3 degrees
      +/-3.3 degrees , p <0.001) and Ha, Hm, and Hp vertebral body heights (Ha, 1.5+/
      2.9 mm; Hm, 2.1+/-2.9 mm; Hp, 0.9+/-2.1 mm; p <0.001) were significant. However,
      the initial height restoration could not be maintained by the 6-week and 1-year
      follow-up. Neither BKP nor RFK could achieve a clinically relevant advantage over
      each other. There was no correlation between pain relief and height restoration
      after kyphoplasty. CONCLUSIONS: Both BKP and RFK had comparable beneficial
      clinical and radiological effects in the treatment of vertebral compression
      fractures. However, neither the actual extent of height restoration nor its loss
      seems to affect the marked pain relief.

PMID- 30213170
TI  - Clinical and Radiological Comparison between Three Different Minimally Invasive
      Surgical Fusion Techniques for Single-Level Lumbar Isthmic and Degenerative
      Spondylolisthesis: Minimally Invasive Surgical Posterolateral Fusion versus
      Minimally Invasive Surgical Transforaminal Lumbar Interbody Fusion versus Midline
      Lumbar Fusion.
AB  - STUDY DESIGN: Retrospective cohort study. PURPOSE: Comparison between three
      different minimally invasive surgical (MIS) fusion techniques for single-level
      lumbar spondylolisthesis. OVERVIEW OF LITERATURE: There has been an increase in
      the development and utilization of MIS techniques for lumbar spine fusion. No
      study has compared the efficacy of MIS-posterolateral fusion (MIS-PLF), MIS
      transforaminal lumbar interbody fusion (MIS-TLIF), and midline lumbar fusion
      (MIDLF) with modified cortical bone trajectory screws for lumbar
      spondylolisthesis. METHODS: Fifty-nine patients with single-level lumbar
      spondylolisthesis and a minimum follow-up period of 1 year were included in this
      study. The MIS-PLF, MIS-TLIF, and MIDLF groups included 22, 15, and 22 patients,
      respectively. The average age of the groups was 70.6, 49.3, and 62.7 years,
      respectively. The evaluation parameters were operation time, intraoperative
      bleeding, serum C-reactive protein (CRP) value, creatine kinase (CK) value, and
      overall functional outcome as per the Japanese Orthopedic Association Back Pain
      Evaluation Questionnaire (JOABPEQ) score. The changes in the lumbar lordosis
      angle (LLA), segmental disc angle (SDA), and disc height were measured. Fusion
      rate, screw loosening, and loss of correction were also assessed. RESULTS: MIDLF
      showed a significantly shorter operation time (111 min), less bleeding amount
      (112.5 mL), and lower values of CRP and CK than the other two techniques. There
      was no significant difference in the JOABPEQ scores of the three groups. MIDLF
      resulted in a greater increase in the LLA and SDA postoperatively. MIDLF and MIS
      TLIF resulted in a significant increase in the middle disc height compared with
      MIS-PLF. MIDLF showed a lower loss of correction after 6 months postoperatively
      (2.6%) than MIS-PLF (5.2%) and MIS-TLIF (4.2%). The fusion rate was 100% in the
      MIDLF and MIS-TLIF groups and 90% in the MIS-PLF group. Screw loosening occurred
      in 10% of the MIS-PLF cases, 7.14% of the MIS-TLIF cases, and 4.76% of the MIDLF
      cases. CONCLUSIONS: MIDLF was the least invasive, and there was no significant
      difference between the three groups in terms of fusion, screw loosening, and
      clinical outcomes.

PMID- 30213171
TI  - Does Recombinant Human Bone Morphogenic Protein 2 Affect Perioperative Blood Loss
      after Lumbar and Thoracic Spinal Fusion?
AB  - STUDY DESIGN: Retrospective cohort design. PURPOSE: This study aimed to determine
      whether recombinant human bone morphogenic protein 2 (rhBMP-2) reduces total
      perioperative blood loss during lumbar and thoracic fusion. OVERVIEW OF
      LITERATURE: Previous studies on rhBMP-2 versus iliac crest bone grafting in
      thoracic and lumbar fusions have yielded mixed results regarding reductions in
      blood loss and have largely neglected the postoperative period when analyzing
      total blood loss. Additionally, these studies have been limited by heterogeneity
      and sample size. METHODS: We analyzed the blood loss patterns of 617 consecutive
      adult patients undergoing lumbar and/or thoracic fusions requiring subfascial
      drain placement at a single institution from January 2009 to December 2016.
      Patients were divided into BMP and non-BMP cohorts, and a propensity score
      analysis was conducted to account for the differences between cohorts. RESULTS:
      At a per-level fused basis, the BMP group exhibited a significant reduction in
      the intraoperative (66.1 mL per-level fused basis; 95% confidence interval [CI],
      127.9 to 4.25 mL; p =0.036) and total perioperative blood loss (100.7 mL per
      level fused basis; 95% CI, 200.9 to 0.5 mL; p =0.049). However, no significant
      differences were observed in an analysis when not controlling for the number of
      levels or when examining the postoperative drain output. CONCLUSIONS: RhBMP-2
      appears to reduce both intraoperative and total blood loss during lumbar and
      thoracic fusions on a per-level fused basis. This total reduction in blood loss
      was achieved via intraoperative effects because RhBMP-2 had no significant effect
      on the postoperative drain output.

PMID- 30213172
TI  - Minimally Invasive Augmented Fixation for Anatomical Reduction of Grade 2 and
      Grade 3 Listhesis in Patients with Osteoporosis.
AB  - STUDY DESIGN: A retrospective study. PURPOSE: To study the efficacy of augmented
      fixation for anatomical reduction of grade 2 and grade 3 listhesis in patients
      with osteoporosis. OVERVIEW OF LITERATURE: Spondylolisthesis in osteoporotic
      patients requiring spinal fixation are associated with complications such as loss
      of surgical construct stability, screw pulling out, and screw loosening.
      Augmented fixation is a novel strategy to achieve necessary construct integrity.
      METHODS: Thirteen consecutive patients with grade 2 or grade 3 listhesis, with
      proven osteoporosis on dual energy X-ray absorptiometry (DEXA) scan, and who
      underwent augmented fixation for reduction of listhesis were retrospectively
      analyzed. In all patients, surgical access was achieved with a fixed 22 mm
      tubular retractor. A modified technique of bilateral, sequential, transforaminal
      decompression and discectomy, followed by reduction of listhesis using
      unilaterally placed augmented screws was employed in all the cases. Patients were
      followed up with plain X-rays at regular intervals to assess for implant
      stability and fusion status. All patients were started on medical treatment for
      osteoporosis. RESULTS: The mean age of the patients was 52.46 years, with 12
      females and one male. The median T-score on DEXA scan was -3.0. Of the 13
      patients, listhesis was at L4-L5 in five and at L5-S1 in eight. Nine patients had
      grade 2 listhesis, while four patients had grade 3 listhesis. Complete reduction
      was achieved in 10 patients. The median duration of follow-up was 18 months.
      Postoperative outcomes were satisfactory in all cases. CONCLUSIONS: Augmented
      fixation is a useful technique for achieving anatomical reduction of listhesis in
      patients with osteoporosis.

PMID- 30213173
TI  - Comparison of Preoperative and Postoperative Parecoxib Administration for Pain
      Control Following Major Spine Surgery.
AB  - STUDY DESIGN: Prospective randomized, double-blind controlled trial. PURPOSE:
      Here, we aim to compare the efficacy and safety of pain control between pre- and
      postoperative parecoxib administration in patients who have undergone major spine
      surgery. OVERVIEW OF LITERATURE: Several studies have compared the efficacy of
      pre- and postoperative administration of parecoxib, which led to inconclusive
      results owing to variation in operative time. Preincisional parecoxib
      administration reduces inflammatory response in major spine surgery requiring
      longer operative time; however, it may not reduce pain as much as parecoxib
      administration immediately after surgery would. METHODS: Totally, 127 patients
      who underwent major spine surgery were randomly divided into three groups: pre
      group, which received 40 mg parecoxib before skin incision and at 12 and 24 hours
      after the first dose; post-group, which received the same dose at wound closure
      and at 12 and 24 hours after the first dose; and control group, which did not
      receive any parecoxib. Efficacy and safety of parecoxib were measured based on
      pain score, morphine consumption, and side effects from both morphine and
      parecoxib at 24 hours after surgery. RESULTS: Initial postoperative pain score,
      postoperative pain score at rest, and accumulative morphine consumption at 24
      hours after surgery were similar between the pre- and post-groups. Despite the
      significantly lower pain score and morphine consumption in both pre- and post
      groups compared with the control group, cumulative morphine consumption at 24
      hours after surgery was reduced by approximately 50% in the pre-group and 46% in
      the post-group compared. Analgesic-related complication incidence was similar in
      all groups. CONCLUSIONS: The timing of parecoxib administration, either before or
      after major spinal surgery, did not affect the safety and analgesic efficacy of
      pain management.

PMID- 30213174
TI  - Zygapophyseal Joint Orientation and Facet Tropism and Their Association with
      Lumbar Disc Prolapse.
AB  - STUDY DESIGN: Cross-sectional study. PURPOSE: To evaluate the association between
      zygapophyseal joint angle (ZJA), facet tropism (FT), and lumbar intervertebral
      disc prolapse (IVDP). OVERVIEW OF LITERATURE: Several studies have shown that FT
      increases the risk of IVDP and have postulated that a more sagittally oriented
      zygapophyseal joint provides less mechanical resistance to axial torque, thereby
      exerting excessive rotational strain on the intervertebral disc, resulting in an
      annular tear. In contrast, other studies have found no definitive association
      between FT and IVDP. Therefore, conclusive evidence regarding the role of FT in
      the pathogenesis of disc prolapse is currently lacking. METHODS: Magnetic
      resonance imaging scans of 426 patients with single-level lumbar IVDP were
      analyzed. Right and left ZJAs of the lumbar segments were measured on axial
      sections. The frequency and severity of FT were determined by calculating the
      absolute difference between the right and left ZJAs. Patients without IVDP at L4
      L5 and L5-S1 served as controls for those with IVDP at L4-L5 and L5-S1,
      respectively. Chi-square test and t -test were used to compare the severity and
      frequency of FT between patients with and without IVDP. The receiver operating
      characteristic analysis was performed to determine the critical FT values that
      were predictive of IVDP. RESULTS: Patients with IVDP exhibited a higher frequency
      (L4-L5: 47% vs. 15.08%; L5-S1: 39.62% vs. 22.69%; p =0.001) and severity (L4-L5:
      7.85 degrees +/-3.5 degrees  vs. 4.05 degrees +/-2.62 degrees ; L5-S1: 7.30
      degrees +/-3.07 degrees  vs. 4.82 degrees +/-3.29 degrees ; p <0.001) of FT than
      those without IVDP. Critical FT values of 5.7 degrees  at L4-L5 and 6 degrees  at
      L5-S1 increased the likelihood of IVDP by a factor of 2.89 and 1.75,
      respectively. CONCLUSIONS: Our results confirm the existence of a significant
      association between lumbar IVDP and FT; however, a causal relationship could not
      be ascertained.

PMID- 30213175
TI  - Mechanisms of Cervical Spine Disc Injury under Cyclic Loading.
AB  - STUDY DESIGN: Determination of human cervical spine disc response under cyclic
      loading. PURPOSE: To explain the potential mechanisms of intervertebral disc
      injury caused by cyclic loading. OVERVIEW OF LITERATURE: Certain occupational
      environments in civilian and military populations may affect the cervical spine
      of individuals by cyclic loading. Research on this mechanism is scarce. METHODS:
      Here, we developed a finite element model of the human C4-C5 disc. It comprised
      endplates, five layers of fibers, a nucleus, and an annulus ground substance. The
      endplates, ground substance, and annular fibers were modeled with elastic,
      hyperviscoelastic, and hyper-elastic materials, respectively. We subjected the
      disc to compressive loading (150 N) for 10,000 cycles at frequencies of 2 Hz
      (low) and 4 Hz (high). We measured disc displacements over the entire loading
      period. We obtained maximum and minimum principal stress and strain and von Mises
      stress distributions at both frequencies for all components. Further, we used
      contours to infer potential mechanisms of internal load transfer within the disc
      components. RESULTS: The points of the model disc displacement versus the loading
      cycles were within the experimental corridors for both frequencies. The principal
      stresses were higher in the ground matrix, maximum stress was higher in the
      anterior and posterior annular regions, and minimum stress was higher along the
      superior and inferior peripheries. The maximum principal strains were radially
      directed, whereas the minimum principal strains were axially/obliquely directed.
      The stresses in the fibers were greater and concentrated in the posterolateral
      regions in the innermost layer. CONCLUSIONS: Disc displacement was lower at high
      frequency, thus exhibiting strain rate stiffening and explaining stress
      accumulation at superior and interior peripheries. Greater stresses and strains
      at the boundaries explain disc injuries, such as delamination. The greater
      development of stresses in the innermost annular fiber layer (migrating toward
      the posterolateral regions) explains disc prolapse.

PMID- 30213177
TI  - Efficacy of Virtual Reality in Upper Limb Rehabilitation in Patients with Spinal
      Cord Injury: A Pilot Randomized Controlled Trial.
AB  - STUDY DESIGN: Pilot randomized controlled trial. PURPOSE: To compare the efficacy
      between virtual reality intervention (using Nintendo Wii) along with conventional
      occupational therapy and conventional occupational therapy alone in improving
      upper limb function in patients with spinal cord injury (SCI). OVERVIEW OF
      LITERATURE: The use of virtual reality has gained importance in the
      rehabilitation sector over the last few years. Nintendo Wii has the potential to
      encourage upper limb function while engaging in an interesting activity, which is
      important in long-term interventions, such as the treatment of SCI. METHODS:
      Overall, 22 patients with SCI participated in the study. They were randomly
      assigned to two groups. Group I received 30 minutes of virtual reality
      intervention (using Nintendo Wii) and 30 minutes of conventional therapy, whereas
      group II received conventional therapy only for 30 minutes. Both groups received
      therapy 3 days a week for 4 weeks. One hand of each patient was identified as the
      target hand based on the inclusion criteria. All patients were assessed at
      baseline, 2 weeks and 4 weeks (post-intervention), and 6 weeks (follow-up). The
      functional ability of the target hand was assessed using the Capabilities of
      Upper Extremity (CUE) questionnaire. Gross motor dexterity was assessed using the
      Box and Block Test (BBT). The level of independence in activities of daily living
      was assessed by the Spinal Cord Independence Measure-Self Report and quality of
      life by the World Health Organization Quality of Life-BREF. RESULTS: After 4
      weeks of intervention, there was no significant difference in improved hand
      function between the groups. Mean scores were higher for group I than for group
      II, with a higher percent change (31.5% in CUE questionnaire and 51.7% in BBT) in
      group I. CONCLUSIONS: Virtual reality along with conventional therapy produces
      similar results in upper limb function as does conventional therapy alone.

PMID- 30213176
TI  - Prognosis of Single Spinal Metastatic Tumors: Predictive Value of the Spinal
      Instability Neoplastic Score System for Spinal Adverse Events.
AB  - STUDY DESIGN: This was a retrospective cohort study. PURPOSE: We evaluated the
      predictive value of the Spinal Instability Neoplastic Score (SINS) system for
      spinal adverse events (SAEs) in patients with single spinal metastatic tumor.
      OVERVIEW OF LITERATURE: The SINS system was developed to assess spinal
      instability in patients with single metastatic spinal tumor. However, the
      system's potential predictive value for SAEs has been partially studied. METHODS:
      This system was applied to a retrospective cohort of 78 patients with single
      spinal metastatic tumors. The patients underwent surgical treatment and were
      postoperatively followed up for at least 2 years or until death. The attribution
      of each score and total SINS to SAE (vertebral compression fracture [VCF] and
      spinal cord compression [SCC]) occurrence was assessed using the Cox proportional
      hazards model. RESULTS: SAEs occurred on average 7 months after diagnosis of
      spinal metastasis. The mean survival rate post diagnosis was 43 months.
      Multivariate analysis using the Cox proportional hazards model revealed that the
      pain (p =0.029) and spinal alignment (p =0.001) scores were significantly related
      to VCF occurrence, whereas the pain (p =0.008) and posterolateral involvement (p
      =0.009) scores were related to SCC occurrence. CONCLUSIONS: Among the components
      of the SINS system, while pain and spinal alignment showed a significant
      association with VCF occurrence, pain and posterolateral involvement showed
      association with SCC occurrence.

PMID- 30213178
TI  - Risk Factors for Cement Loosening after Vertebroplasty for Osteoporotic Vertebral
      Fracture with Intravertebral Cleft: A Retrospective Analysis.
AB  - STUDY DESIGN: Retrospective case-control study. PURPOSE: To evaluate the primary
      outcomes and radiographic results of percutaneous vertebroplasty (PVP) in
      patients with singlelevel osteoporotic vertebral fracture (OVF) with
      intravertebral cleft (IVC) to identify the risk factors for cement loosening
      after PVP. OVERVIEW OF LITERATURE: PVP is a widely accepted method for managing
      painful OVF; however, cement loosening occasionally occurs with poor outcomes.
      METHODS: This retrospective study involved 195 patients treated with PVP for
      single-level OVF with IVC. Six months thereafter, the primary outcomes were
      evaluated using the Visual Analog Scale (VAS) for back pain and the modified
      Oswestry Disability Index. Computed tomography was conducted to detect cement
      loosening. Possible risk factors, such as age, sex, wedging angle, intravertebral
      instability, Parkinson's disease, spinous process fracture, ankylosing spinal
      hyperostosis, split vertebrae, and adjacent intervertebral vacuum, were assessed.
      RESULTS: Forty-nine patients (25%) experienced cement loosening 6 months after
      PVP. The mean VAS scores were significantly higher in patients with cement
      loosening than in those without (50 vs. 26 mm, respectively; p <0.01). Cement
      loosening was closely associated with intravertebral instability (odds ratio
      [OR], 1.20; 95% confidence interval [CI], 1.04-1.40; p =0.015), Parkinson's
      disease (OR, 54.31; 95% CI, 4.47-659.53; p =0.002), spinous process fracture (OR,
      7.11; 95% CI, 1.65-30.60; p =0.009), and split vertebrae (OR, 11.59; 95% CI, 1.64
      82.02; p =0.014). CONCLUSIONS: Patients with cement loosening experienced worse
      back pain than those without cement loosening. The important risk factors that
      influenced cement loosening after PVP were high intravertebral instability,
      Parkinson's disease, spinous process fracture, and split vertebrae.

PMID- 30213179
TI  - Lumbar Extensor Muscle Size and Isometric Muscle Strength in Women with
      Symptomatic Lumbar Degenerative Diseases.
AB  - STUDY DESIGN: A cross-sectional design. PURPOSE: To determine the characteristics
      of lumbar extensor muscle (LEM) size and isometric muscle strength and examine
      their correlations in women with lumbar degenerative diseases (LDDs). OVERVIEW OF
      LITERATURE: Many studies have evaluated the relationship between muscle size and
      strength, but the results have been controversial. METHODS: Seventy-four female
      patients (mean age, 66 years) who consecutively underwent posterior lumbar
      interbody fusion (L1-S1) were recruited. The cross-sectional area (CSA) of the
      back extensor muscles was measured between L1-2 to L5-S1, and the total sum of
      the CSAs at each disc level was calculated. Back extensor muscle strength was
      evaluated using a MedX lumbar extension machine. The Oswestry Disability Index
      (ODI, 0-100) and Visual Analog Scale (VAS, 0-10) of lower back pain were
      determined. RESULTS: The mean CSAs of the LEM at each level (L1/2-L5/S1) and the
      total sum were 34.3, 36.3, 35.1, 31.4, 21.9, and 156.2 cm2, respectively. The
      mean isometric strength at each angle (range, 0 degrees -72 degrees ) was 32.5,
      50.1, 72.0, 88.7, 100.7, 112.2, and 126.2 ft-lb, respectively. The mean ODI and
      VAS scores were 54.6 and 6.6, and the mean body weight and body mass index (BMI)
      were 59.9 kg and 24.9 kg/m2, respectively. The CSAs of the upper lumbar level (L1
      4) and the total sum of the CSAs were associated with isometric strength, which
      was negatively correlated with patients' age and ODI and positively associated
      with body weight and BMI, mainly at higher lumbar flexion angles (48 degrees -72
      degrees ). CONCLUSIONS: In women with LDD, LEM sizes of the upper lumbar levels
      (L1-4) were larger than those of the lower levels (L4-S1) and were positively
      associated with muscle strength. The upper lumbar levels in patients with LDDs
      appear to play a compensatory role when degenerative lesions are present in the
      lower lumbar levels.

PMID- 30213181
TI  - A Potential Therapy Using Engineered Stem Cells Prevented Malignant Melanoma in
      Cellular and Xenograft Mouse Models.
AB  - Purpose: In the present study, human neural stem cells (hNSCs) with tumor-tropic
      behavior were used as drug delivery vehicle to selectively target melanoma. A
      human neural stem cell line (HB1.F3) was transduced into two types: one expressed
      only the cytosine deaminase (CD) gene (HB1.F3.CD) and the other expressed both CD
      and human interferon-beta (IFN-beta) genes (HB1.F3.CD.IFN-beta). Materials and
      Methods: This study verified the tumor-tropic migratory competence of engineered
      hNSCs on melanoma (A375SM) using a modified Boyden chamber assay in vitro and CM
      DiI staining in vivo. The antitumor effect of HB1.F3.CD and HB1.F3.CD.IFN-beta on
      melanoma was also confirmed using an MTT assay in vitro and xenograft mouse
      models. Results: A secreted form of interferon-beta from the HB1.F3.CD.IFN-beta
      cells modified the epithelial-mesenchymal transition (EMT) process and metastasis
      of melanoma. 5-fluorouracil (5-FU) treatment also accelerated the expression of
      the pro-apoptotic protein BAX and decelerated the expression of the anti
      apoptotic protein Bcl-xL on melanoma cell line. Conclusion: Our results
      illustrate that engineered hNSCs prevented malignant melanoma cells from
      proliferating in the presence of the prodrug, and the form that secreted
      interferon-beta intervened in the EMT process and melanoma metastasis. Hence,
      neural stem cell-directed enzyme/prodrug therapy is a plausible treatment for
      malignant melanoma.

PMID- 30213180
TI  - Efficacy of Corrective Surgery for Gait and Energy Expenditure in Patients with
      Scoliosis: A Literature Review.
AB  - The aim of this literature review was to evaluate selected original papers that
      measured gait parameters and energy expenditure in idiopathic scoliosis (IS)
      treated with surgical intervention. IS is a progressive growth disease that
      affects spinal anatomy, mobility, and left-right trunk symmetry. Consequently, IS
      can modify human gait. Spinal fusions remain the primary approach to correcting
      scoliosis deformities, thereby halting progression. Using the population
      intervention comparison outcome measure framework and selected keywords, 15
      studies that met the inclusion criteria were selected. Alteration of spatial and
      temporal variables in patients with IS was contradictory among the selected
      studies. Ankle and foot kinematics did not change after surgery; however, pelvic
      and hip frontal motions increased and pelvic rotation decreased following
      surgery. Patients with IS continued to show excessive energy expenditure
      following surgery in the absence of a physical rehabilitation protocol. Spinal
      surgery may be considered for gait improvement and IS treatment. There were
      inadequate data regarding the effect of corrective surgery on the kinetics,
      energy expenditure, and muscle activity parameters.

PMID- 30213182
TI  - Unveiling the Takai Olefination Reagent via Tris( tert-butoxy)siloxy Variants.
AB  - The elusive Takai olefination reagent, namely, the iodo-methylidene Cr(III)
      complex [Cr2Cl4(CHI)(thf)4], has been isolated by careful handling of the
      reaction between CrCl2 and CHI3 in THF at -35  degrees C. Alternatively,
      treatment of [Cr(OSi(O tBu)3)2] with CHI3 gave the mixed-valent dihalido
      methanide complex [CrII/III2I2(OSi(O tBu)3)2(CHI2)], featuring a Cr(III)-CHI2
      moiety. In the presence of TMEDA nucleophilic attack at CHI2 occurred generating
      the zwitterionic species [CrIII(OSi(O tBu)3)2(tmeda-CHI)][I]. Complexes
      [Cr2Cl4(CHI)(thf)4] and [CrII/III2I2(OSi(O tBu)3)2(CHI2)] were screened for their
      ability to induce monohalido olefination of benzaldehyde. Remarkably, both
      complexes promote olefination, with [Cr2Cl4(CHI)(thf)4] accomplishing the same E
      selectivity as Takai 's original mixture. Complex [CrII/III2I2(OSi(O
      tBu)3)2(CHI2)], however, appeared to give preferentially Z isomer, corroborating
      the monoiodo-methylidene species Cr(III)-CHI-Cr(III) as the active olefination
      component of the original in situ generated Takai reagent mixture.

PMID- 30213183
TI  - Robust Micron-Sized Silicon Secondary Particles Anchored by Polyimide as High
      Capacity, High-Stability Li-Ion Battery Anode.
AB  - Silicon is an attractive high-capacity anode material for lithium-ion battery.
      With the help of nanostructures, cycling performance of silicon anode has
      improved significantly in the past couple of years. However, three major
      shortcomings associated with nanostructures still need to be addressed, namely,
      their high surface area, low tap density, and poor scalability. Herein, we
      present a facile and practical method to produce micron-sized Si secondary
      particle cluster (SiSPC) with a high tap density and a low surface area from bulk
      Si by high-energy ball-milling. By coupling SiSPC with a mechanically robust
      polyimide binder, more than 95% of the initial capacity is retained after 500
      cycles at 3500 mA g-1 (1C rate). Reversibility of electrode thickness change is
      confirmed by in situ dilatometry. In addition, the polyimide binder suppresses
      the surface reaction of the particles with electrolyte, resulting in a high
      Coulombic efficiency of 99.7%. Excellent cycling performance is obtained even for
      thick electrodes with an areal capacity of 3.57 mAh cm-2, similar to those in
      commercial lithium-ion batteries. The presented Si electrode system has a high
      volumetric capacity of 598 mAh cm-3, which is higher than that of the commercial
      graphite anode materials.

PMID- 30213184
TI  - Synthesis of 2-Tetrazolyl-Substituted 3-Acylpyrroles via a Sequential Ugi
      Azide/Ag-Catalyzed Oxidative Cycloisomerization Reaction.
AB  - A new efficient Ag-catalyed cascade cycloisomerization/aerobic oxidation reaction
      of a Ugi-azide adduct for the preparation of 3-acylpyrroles using molecular
      oxygen as the terminal oxidant has been developed. A series of 2-tetrazolyl
      substituted 3-acylpyrroles were obtained in 62-89% yields from readily available
      enynals 1, primary amines 2, isocyanides 3, and trimethylsilyl azide 4 in the
      presence of a catalytic amount of AgNO3 and DMAP under an O2 atmosphere.

PMID- 30213185
TI  - Electrochemical and Surface-Plasmon Correlation of a Serum-Autoantibody
      Immunoassay with Binding Insights: Graphenyl Surface versus Mercapto-Monolayer
      Surface.
AB  - We present here the correlation of picomolar affinities between surface-plasmon
      and electrochemical immunoassays for the binding of serum glutamic acid
      decarboxylase 65 autoantibody (GADA), a biomarker of type 1 diabetes (T1D), to
      its antigen GAD-65. Carboxylated (~5.0%)-graphene-modified immunoassembly on a
      gold surface-plasmon chip or on an electrochemical array provided significantly
      larger binding affinity, higher sensitivity, and lower detection limits than a
      self-assembled monolayer surface of mercaptopropionic acid (MPA). Estimation of
      the relative surface -COOH groups by covalent tagging of an electroactive
      aminoferrocene showed that the graphenyl surface displayed a greater number of 
      COOH groups (9-fold) than the MPA surface. X-ray-photoelectron-spectroscopy
      analysis showed more C-O and C?O functionalities on the graphene-COOH surface
      than on the MPA surface. The graphene-COOH coating on gold exhibited ~5.5-fold
      enhancement of plasmon signals compared with a similar coating on a plain glass
      surface. In summary, this article provides a quantitative comparison of
      carboxylated graphene with a mercapto-monolayer immunoassembly. Additionally, we
      propose that the binding-constant value can be useful as a quality-control
      checkpoint for reproducible and reliable production of large-scale biosensors for
      clinical bioassays.

PMID- 30213186
TI  - Halide-Induced Self-Limited Growth of Ultrathin Nonlayered Ge Flakes for High
      Performance Phototransistors.
AB  - 2D nonlayered materials have attracted intensive attention due to their unique
      surface structure and novel physical properties. However, it is still a great
      challenge to realize the 2D planar structures of nonlayered materials owing to
      the naturally intrinsic covalent bonds. Ge is one of them with cubic structure
      impeding its 2D anisotropic growth. Here, the ultrathin single-crystalline Ge
      flakes as thin as 8.5 nm were realized via halide-assisted self-limited CVD
      growth. The growth mechanism has been confirmed by experiments and theoretical
      calculations, which can be attributed to the preferential growth of the (111)
      plane with the lowest formation energy and the giant interface distortion effect
      of the Cl-Ge motif. Excitingly, a Ge flake-based phototransistor shows excellent
      performances such as a high hole mobility of ~263 cm2 V-1 s-1, a high
      responsivity of ~200 A/W, and fast response rates (taurise = 70 ms, taudecay = 6
      ms), suggesting its great potential in the applications of electronics and
      optoelectronics.

PMID- 30213187
TI  - Imidazolium-Based Ionic Liquids Affect Morphology and Rigidity of Living Cells:
      An Atomic Force Microscopy Study.
AB  - The study of the toxicity, biocompatibility, and environmental sustainability of
      room-temperature ionic liquids (ILs) is still in its infancy. Understanding the
      impact of ILs on living organisms, especially from the aquatic ecosystem, is
      urgent, since large amounts of these substances are starting to be employed as
      solvents in industrial chemical processes, and on the other side, evidence of
      toxic effects of ILs on microorganisms and single cells have been observed. To
      date, the toxicity of ILs has been investigated by means of macroscopic assays
      aimed at characterizing the effective concentrations (like the EC50) that cause
      the death of a significant fraction of the population of microorganisms and
      cells. These studies allow us to identify the cell membrane as the first target
      of the IL interaction, whose effectiveness was correlated to the lipophilicity of
      the cation, i.e., to the length of the lateral alkyl chain. Our study aimed at
      investigating the molecular mechanisms underpinning the interaction of ILs with
      living cells. To this purpose, we carried out a combined topographic and
      mechanical analysis by atomic force microscopy of living breast metastatic cancer
      cells (MDA-MB-231) upon interaction with imidazolium-based ILs. We showed that
      ILs are able to induce modifications of the overall rigidity (effective Young's
      modulus) and morphology of the cells. Our results demonstrate that ILs act on the
      physical properties of the outer cell layer (the membrane linked to the actin
      cytoskeleton), already at concentrations below the EC50. These potentially toxic
      effects are stronger at higher IL concentrations, as well as with longer lateral
      chains in the cation.

PMID- 30213189
TI  - Benchmarking Bicontinuous Nanospheres against Polymersomes for in Vivo
      Biodistribution and Dual Intracellular Delivery of Lipophilic and Water-Soluble
      Payloads.
AB  - Bicontinuous nanospheres (BCNs) are polymeric analogs to lipid cubosomes,
      possessing cubic liquid crystalline phases with high internal surface area,
      aqueous channels for loading hydrophilic molecules, and high hydrophobic volume
      for lipophilic payloads. Primarily due to difficulties in scalable and consistent
      fabrication, neither controlled delivery of payloads via BCNs nor their organ or
      cellular biodistributions following in vivo administration have been demonstrated
      or characterized. We have recently validated flash nanoprecipitation as a rapid
      method of assembling uniform monodisperse 200-300 nm diameter BCNs from
      poly(ethylene glycol) -b-poly(propylene sulfide) (PEG -b-PPS) co-polymers. Here,
      we compare these BCNs both in vitro and in vivo to 100 nm PEG -b-PPS polymersomes
      (PSs), which have been well characterized as nanocarriers for controlled delivery
      applications. Using a small molecule fluorophore and a fluorescently tagged
      protein as respective lipophilic and water-soluble model cargos, we demonstrate
      that BCNs can achieve significantly higher encapsulation efficiencies for both
      payloads on a per unit mass basis. At time points of 4 and 24 h after intravenous
      administration to mice, we found significant differences in organ-level uptake
      between BCNs and PSs, with BCNs showing reduced accumulation in the liver and
      increased uptake in the spleen. Despite these organ-level differences, BCNs and
      PSs displayed strikingly similar uptake profiles by immune cell populations in
      vitro and in the liver, spleen, and blood, as assayed by flow cytometry. In
      conclusion, we have found PEG -b-PPS BCNs to be well suited for dual loading and
      delivery of molecular payloads, with a favorable organ biodistribution and high
      cell uptake by therapeutically relevant immune cell populations.

PMID- 30213191
TI  - Impact of mild traumatic brain injury understanding on intended help-seeking
      behaviour.
AB  - Children do not always receive adequate medical attention following a mild
      traumatic brain injury (mTBI), despite the necessity of this treatment. Adult
      mTBI knowledge may be one factor that affects if a child receives medical
      attention, but little is known about association between mTBI knowledge and help
      seeking behaviour. Participants were 212 females and 58 males, including 84
      parents, with a mean age of 35.57 years (standard deviation = 10.96). A
      questionnaire evaluated participants' understanding of mTBI and vignettes to
      evaluate behavioural intentions regarding help-seeking behaviour after an mTBI.
      Only 40.0% of participants were able to recall an adequate number of mTBI
      symptoms (5+). Surprisingly, mTBI history was not associated with better mTBI
      knowledge, t(df, 268) = 1.29, p = .20. Similarly, knowing a close friend or
      family member with mTBI was not associated with higher mTBI knowledge, t(df =
      268) = .81, p = .4. Further, neither mTBI symptom knowledge nor vignette child
      age (young = 5 years, older = 15 years) significantly predicted participants'
      cited intentions to perform help-seeking behaviour. Consistent with the existing
      research, the current study demonstrates a continued lack of mTBI knowledge in
      the general population. However, this may not be a factor that influences an
      adult's decision to take a child to hospital following mTBI. Future research
      should investigate the association between help-seeking intentions and actual
      behaviour in relation to paediatric mTBI.

PMID- 30213190
TI  - Anticholinergic Burden in Hospice Patients With Dementia.
AB  - BACKGROUND: End-of-life (EOL) patients with dementia have an increased risk for
      anticholinergic toxicities due to age-related pharmacokinetic and physiologic
      changes in conjunction with an increased susceptibility to drug-induced cognitive
      impairments. Despite this well-documented risk, the use of drugs with
      anticholinergic properties (DAPs) remains prevalent in EOL patients with
      dementia. OBJECTIVE: The aims of this study were to describe prescribing patterns
      and characterize anticholinergic burden among hospice patients with dementia, as
      measured by the Anticholinergic Cognitive Burden (ACB) scale. METHODS: This was a
      retrospective review of a national hospice patient information database. Patients
      included were admitted on January 1, 2016, discharged by death by December 31,
      2016, and had a primary diagnosis of dementia. Patients' anticholinergic burden
      was calculated using ACB scores. RESULTS: A total of 1283 patients met the
      inclusion criteria. Of those, 37.1% (n = 476) were prescribed at least 1 DAP.
      Specifically, 28.9% (n = 371) were prescribed 1 DAP, 6.6% (n = 84) were
      prescribed 2 DAPs, 1.6% (n = 20) were prescribed 3 DAPs, and 0.08% (n = 1) were
      prescribed 4 DAPs. The majority of patients prescribed a DAP had an ACB score of
      3 (n = 359, 75.4%) and an average ACB score of 3.8. The most common DAPs
      prescribed in patients with an ACB score of 2 or higher were quetiapine (n = 202,
      42.4%), atropine (n = 155, 32.6%), hyoscyamine (n = 61, 12.8%), olanzapine (n =
      46, 9.6%), and scopolamine (n = 35, 7.4%). CONCLUSION: Due to the limited benefit
      and increased harms with the use of DAPs, providers should aim to maximize
      nonpharmacologic options. By reducing the use of the top 5 DAPs identified in
      this study, the quality of life and care for EOL patients with dementia can
      potentially be improved.

PMID- 30213188
TI  - Replacement of the Distal Histidine Reveals a Noncanonical Heme Binding Site in a
      2-on-2 Hemoglobin.
AB  - Heme ligation in hemoglobin is typically assumed by the "proximal" histidine.
      Hydrophobic contacts, ionic interactions, and the ligation bond secure the heme
      between two alpha-helices denoted E and F. Across the hemoglobin superfamily,
      several proteins also use a "distal" histidine, making the native state a bis
      histidine complex. The group 1 truncated hemoglobin from Synechocystis sp. PCC
      6803, GlbN, is one such bis-histidine protein. Ferric GlbN, in which the distal
      histidine (His46 or E10) has been replaced with a leucine, though expected to
      bind a water molecule and yield a high-spin iron complex at neutral pH, has low
      spin spectral properties. Here, we applied nuclear magnetic resonance and
      electronic absorption spectroscopic methods to GlbN modified with heme and amino
      acid replacements to identify the distal ligand in H46L GlbN. We found that
      His117, a residue located in the C-terminal portion of the protein and on the
      proximal side of the heme, is responsible for the formation of an alternative bis
      histidine complex. Simultaneous coordination by His70 and His117 situates the
      heme in a binding site different from the canonical site. This new holoprotein
      form is achieved with only local conformational changes. Heme affinity in the
      alternative site is weaker than in the normal site, likely because of strained
      coordination and a reduced number of specific heme-protein interactions. The
      observation of an unconventional heme binding site has important implications for
      the interpretation of mutagenesis results and globin homology modeling.

PMID- 30213192
TI  - Beyond Lipids: Antiarrhythmic Effects of Statins.

PMID- 30213193
TI  - Predictive Factors for Functional Outcomes After Intravenous Thrombolytic Therapy
      in Acute Ischemic Stroke.
AB  - The objective of our study is to detect the patient group that will most benefit
      from intravenous (IV) thrombolytic therapy by showing predictive factors of good
      functional outcomes. The present study covers 88 patients who were admitted to
      our clinic within the first 4.5 hours from the onset of stroke symptoms,
      diagnosed with acute ischemic stroke and who received IV thrombolytic therapy
      between May 2014 and June 2017 as a result of a retrospective analysis of a
      database prospectively collected. The patients with a score of <=2 on modified
      Rankin scale within 3 months were accepted as good functional outcome and those
      with a score of >2 were accepted as poor functional outcome. As a result, within
      the period of 3 months posttreatment, good functional outcomes were obtained in
      45 (51.1%) patients and poor functional outcomes were obtained in 43 (48.9%)
      patients. In comparisons, cardioembolic stroke group was statistically
      significantly higher in the good functional outcome group ( P = .03).
      Pretreatment National Institute of Health Stroke Scale (NIHSS) scores ( P <
      .001), presence of proximal hyperintense middle cerebral artery sign in
      noncontrast computed brain tomography ( P = .03), and being aged >=80 and older (
      P = .04) were markedly higher in the group with poor functional outcomes. In
      conclusion, our study demonstrated that cardioembolic strokes may have an impact
      on good functional outcomes and being aged 80 and older, presence of proximal
      HMCAS in computed brain tomography, and pretreatment NIHSS scores may have an
      impact on poor functional outcomes.

PMID- 30213194
TI  - Association between Inhaled Corticosteroid Use and Pulmonary Nontuberculous
      Mycobacterial Infection.
AB  - RATIONALE: Nontuberculous mycobacterial (NTM) pulmonary disease prevalence is
      increasing. OBJECTIVES: To determine the association between the use of inhaled
      corticosteroids and the likelihood of NTM pulmonary infection among individuals
      with treated airway disease. METHODS: We conducted a case-control study of
      subjects with airway disease with and without NTM pulmonary infection (based on
      mycobacterial respiratory cultures) between 2000 and 2010 in northern California.
      We quantified the use of inhaled corticosteroids, other airway disease
      medications, and healthcare use within 6 months of NTM pulmonary infection
      identification. We used 1:10 case-control matching and conditional logistic
      regression to evaluate the association between the duration and cumulative dosage
      of inhaled corticosteroid use and NTM pulmonary infection. RESULTS: We identified
      248 cases with NTM pulmonary infection with an estimated rate of 16.4 cases per
      10,000 subjects treated for airway disease. The median interval between treated
      airway disease cohort entry (defined as date of patient filling the third airway
      disease treatment prescription) and NTM case identification was 1,217 days.
      Compared with control subjects, subjects with NTM pulmonary infection were more
      likely to use airway disease medications including systemic steroids; they were
      also more likely to use health care. Any inhaled corticosteroids use between 120
      days and 2 years before cohort entry was associated with substantially increased
      odds of NTM infection. For example, the adjusted odds ratio for NTM infection
      among inhaled corticosteroid users in a 2-year interval was 2.51 (95% confidence
      interval, 1.40-4.49; P < 0.01). Increasing cumulative inhaled corticosteroid dose
      was also associated with greater odds of NTM infection. CONCLUSIONS: Inhaled
      corticosteroid use, and particularly high-dose inhaled corticosteroid use, was
      associated with an increased risk of NTM pulmonary infection.

PMID- 30213195
TI  - Clinical Significance of Squamous Differentiation in Urothelial Carcinoma of the
      Bladder.
AB  - The prognostic value of squamous differentiation (SD) in urothelial carcinoma
      (UC) of the bladder is unclear. The aim of this study was to identify the
      clinical significance of SD in UC in terms of oncological outcomes in patients
      undergoing radical cystectomy (RC). We evaluated consecutive patients with muscle
      invasive bladder cancer (MIBC; clinical T2-4aN0M0) treated with RC at our
      institution from March 2003 to March 2017. We enrolled 20 and 81 patients with UC
      with SD (UCSD) and pure UC, respectively. Postoperative survival outcomes were
      compared between the patients with UCSD and pure UC using the Kaplan-Meier
      method. Pre- and postcystectomy factors that influenced the overall survival (OS)
      and recurrence-free survival (RFS) were investigated in these patients.
      Multivariate Cox regression models were used to identify the predictors of OS and
      RFS. With a median follow-up time of 31 months, the 5-year OS rate of the UCSD
      and pure UC groups was 41.1% and 69.7% ( P = .002) and the 5-year RFS rate was
      51.8% and 59.5% ( P = .027), respectively. The shape of the Kaplan-Meier curves
      for UCSD suggested a more rapid course of the disease within the first 2 years
      than observed in pure UC. Multivariate analyses suggested that SD in UC was
      significantly associated with OS (hazard ratio [HR]: 4.22; 95% confidence
      interval [CI]: 1.20-14.8; P = .024) and close to significance for a lower RFS
      (HR: 2.13, 95% CI: 0.74-6.15, P = .064). Our results indicate that SD may be an
      independent predictor of OS and RFS in UC of MIBC in patients undergoing RC.

PMID- 30213196
TI  - Exploratory Study of Associations Between DNA Repair and Oxidative Stress Gene
      Polymorphisms and Cognitive Problems Reported by Postmenopausal Women With and
      Without Breast Cancer.
AB  - PURPOSE: Women with breast cancer report varying frequencies of cognitive
      problems during adjuvant systemic therapy. This variability suggests latent
      subgroups. Therefore, we identified latent subgroups of self-reported cognitive
      problems among postmenopausal women with and without breast cancer. We explored
      associations between membership in these subgroups and (a) demographic, clinical,
      and symptom characteristics and (b) variations in candidate gene polymorphisms.
      METHODS: We evaluated frequency of cognitive problems using the Patient
      Assessment of Own Functioning Inventory. Growth mixture modeling identified
      latent subgroups over 18 months of adjuvant systemic therapy and at matched time
      points for women without cancer ( N = 331). We evaluated for differences among
      subgroups in demographic, clinical, and symptom characteristics and in 41 single
      nucleotide polymorphisms in 10 candidate genes involved in DNA repair and
      oxidative stress pathways ( n = 199). We modeled associations between genotypes
      and subgroup membership using multinomial logistic regression. RESULTS: We
      identified three latent subgroups: more frequent, persistent, and almost never.
      Receipt of chemotherapy plus anastrozole, depressive symptoms, and baseline
      neuropathic symptoms increased the odds of belonging to the more frequent
      subgroup. Anxiety and depressive symptoms increased the odds of belonging to the
      persistent subgroup. With covariates controlled for, carrying the ERCC5 rs873601
      G minor allele increased the odds of reporting more frequent cognitive problems.
      CONCLUSIONS: Chemotherapy plus anastrozole, depressive symptoms, and presence of
      neuropathic symptoms may predict more frequent cognitive problems during systemic
      therapy that later resolve. Mood dysregulation before therapy may predict
      persistent cognitive problems during therapy. ERCC5 genotype may influence
      frequency of cognitive problems after controlling for these risk factors.

PMID- 30213197
TI  - Comparison of Efficacy between Ramipril and Carvedilol on Limiting the Expansion
      of Abdominal Aortic Aneurysm in Mouse Model.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) is a common condition that may be life
      threatening when it is unrecognized. The aim of this study is to evaluate and
      compare the efficacy of ramipril and carvedilol on limiting AAA expansion in
      mouse model. METHODS AND RESULTS: A total of 36 experimental AAA mouse model was
      induced with the continuous infusion of angiotensin II (Ang II) in 20-week-old
      male apolipoprotein E-deficient mice. They were randomly divided into 3 treatment
      groups and fed orally for 8 weeks; saline alone, ramipril (2.5 mg/30g/d), or
      carvedilol (3.125 mg/30g/d), respectively. Aortic diameter (AD) was measured by
      micro-computed tomography, and the level of biomarkers of aortic tissue such as
      monocyte chemoattractant protein-1 (MCP-1) and tissue inhibitor matrix
      metalloproteinase-1 (TIMP-1) was evaluated. After treatment, AD of both ramipril
      and carvedilol group was smaller than in the saline group. The percentage change
      of AD in both ramipril and carvedilol groups was significantly smaller than that
      of the saline group. Pathologic examination revealed relatively well-preserved
      aortic walls in the ramipril group compared to the carvedilol and saline groups.
      The level of MCP-1 was markedly decreased in both the ramipril and carvedilol
      groups compared to the saline group. The level of TIMP-1 was higher in the
      carvedilol group when compared to either the saline or ramipril groups.
      CONCLUSIONS: Ramipril and carvedilol treatment shows similar efficacy in limiting
      AAA expansion in mouse model. Future clinical research would be warranted to
      validate these results.

PMID- 30213199
TI  - Rotation Advancement in Cleft Nose Rhinoplasty-Buccal Mucosal Grafts Serves as a
      Powerful Tool.

PMID- 30213200
TI  - Time in the Therapeutic Range for Assessing Anticoagulation Quality in Patients
      Receiving Continuous Unfractionated Heparin.
AB  - Due to variable pharmacokinetic properties, therapeutic anticoagulation with
      continuous unfractionated heparin (UFH) requires ongoing laboratory monitoring,
      generally with activated partial thromboplastin time (aPTT). In the ambulatory
      setting, clinicians who manage warfarin therapy often use time in the therapeutic
      range (TTR) to estimate a percentage of time the international normalized ratio
      is therapeutic. We applied the TTR concept to aPTT monitoring for therapeutic UFH
      and used 2 methodologies for estimation: percentage of aPTT values in range
      (%aIR) and a modification of the Rosendaal method (mod-Rosendaal). This study
      included adult inpatients admitted between September 30, 2015, and September 30,
      2016, at Brigham and Women's Hospital. For each patient, all available aPTT
      values were extracted to calculate 2 individual TTRs according to each
      methodology. Comparison between methods was performed using Student t test, and
      correlation was assessed with simple linear regression. A total of 255 patients
      were included in this study. The major outcome of TTR estimation was
      significantly higher using mod-Rosendaal (43.7% [26.5%]) versus %aIR (37.7%
      [25.7%], P = .012) by a mean difference of 6% points (95% confidence interval:
      1.3-10.7). Time in the therapeutic range estimated by mod-Rosendaal significantly
      correlated with those estimated by %aIR ( r = 0.84, P < .001). Further studies
      should evaluate the correlation between TTR and clinical outcomes and establish a
      benchmark for quality therapeutic anticoagulation with continuous UFH.

PMID- 30213198
TI  - Cervical Cancer, Human Papillomavirus Infection, and Vaccine-Related Knowledge:
      Awareness in Chinese Women.
AB  - Cervical cancer (CC) has a high incidence and mortality and is accompanied by
      lack of organized CC screening programs, lack of health-care facilities, and a
      lack of human papillomavirus (HPV) vaccination among female population in the
      world, particularly China. We recruited 487 females who visited the outpatient
      department of the First People's Hospital of Yunnan Province from November 2015
      to January 2016 to complete a standardized-designed questionnaire. We found that
      only 39.6% of the females knew about the role of HPVs in the development of
      cervical cancer. Moreover, none of the females knew that HPV could cause penile
      carcinomas, perianal carcinomas, and head and neck carcinomas. The majority of
      the participants acquired information about cervical cancer, HPV, and the HPV
      vaccine from medical workers. Only 15.6% of the recruited females had heard about
      the HPV vaccine. The overall HPV vaccine acceptance rate was higher (91.2%) if
      the vaccine was available free of cost. In this study, we found high
      acceptability of the HPV vaccine in Chinese women and high awareness about
      cervical cancer. However, very low levels of knowledge about HPVs and their role
      in cancer development among the recruited women is alarming. Therefore, it is
      very important to initiate educational programs to raise awareness and knowledge
      about cervical cancer, HPV, and the HPV vaccine in this region.

PMID- 30213201
TI  - Facial solitary morphea profunda presenting with painful trigeminal neuropathy: A
      case report.
AB  - Background Localized facial scleroderma usually presents as frontal linear
      morphea or progressive hemifacial atrophy. Only isolated cases of trigeminal
      painful neuropathy have been described. Case report A 43-year-old woman developed
      an oval lesion on the right cheek. After 1 year, she noticed constant "pulling"
      pain and episodes of lancinating pain, both spontaneous and triggered by chewing
      and cold drinks. She was diagnosed with solitary morphea profunda and CT scan,
      ultrasonography, cranial MRI and biopsy were completed. Methylprednisolone (1
      gr/day for 3 days) was prescribed. For pain, gabapentin, oxcarbazepine,
      amitryptiline, pregabalin and eslicarbacepine were all ineffective. A capsaicin
      patch was placed with prolonged benefit. Later on, the pain slightly worsened;
      occipital blockade was effective and methotrexate was recommended. Conclusion
      This is the first case of solitary morphea profunda associated with painful
      trigeminal neuropathy. Treatment should include immunosuppressants and treatment
      of neuropathic pain, in which local therapies seem particularly beneficial.

PMID- 30213202
TI  - A prospective pilot study of the effect on catecholamines of mindfulness training
      vs pharmacological prophylaxis in patients with chronic migraine and medication
      overuse headache.
AB  - Aim To address whether, in patients with chronic migraine and medication overuse
      headache, mindfulness-based treatment is associated with changes in plasma levels
      of catecholamines and elusive amines that are similar to those observed in
      patients undergoing pharmacological prophylaxis. Methods In this non-randomized,
      clinic-based effectiveness study, patients aged 18-65, with a history of chronic
      migraine >= 10 years and overuse of triptans or non-steroidal anti-inflammatory
      drugs >= 5 years, were enrolled. Upon completion of a structured withdrawal
      program, patients received either pharmacological prophylaxis or six weekly
      sessions of mindfulness-based treatment and were followed for 12 months. Daily
      headache diaries were used to record headache frequency and medication intake;
      catecholamines (noradrenaline, epinephrine and dopamine) and levels of elusive
      amines were assayed from poor platelet plasma. Results Complete follow-up data
      were available for 15 patients in the pharmacological prophylaxis-group (14
      females, average age 44.1) and 14 in the mindfulness treatment-group (all
      females, average age 46.4), and all variables were comparable between groups at
      baseline. At 12 months, significant improvement ( p < .001) was found in the
      pharmacological prophylaxis group for headache frequency and medication intake
      (by 51% and 48.7%, respectively), noradrenaline, epinephrine and dopamine (by
      98.7%, 120.8% and 501.9%, respectively); patients in the mindfulness treatment
      group performed similarly. For elusive amines, no longitudinal changes were
      found. Conclusions The similar improvement trends observed in the two groups of
      patients further support the utility of mindfulness-based treatment in migraine
      care, and reinforce the hypothesis that alteration and normalization of tyrosine
      metabolism are implicated in migraine chronification and in remission of chronic
      migraine.

PMID- 30213203
TI  - Comparison of Total Joint Replacement Rate Between Patients With Hemophilia A and
      Patients With Hemophilia B: A Population-Based and Retrospective Cohort Study.
AB  - Recurrent hemarthrosis in patients with hemophilia (PWH) results in chronic
      arthropathy requiring total joint replacement (TJR). This study aimed to compare
      the difference in TJR rate between patients with hemophilia A (HA) and hemophilia
      B (HB). A final total of 935 PWH (782 HA and 153 HB) without inhibitors were
      collected from the Taiwan's National Health Insurance Research Database between
      1997 and 2013. Demographics, clinical characteristics, and TJR rate were compared
      between the 2 groups. The annual use of clotting factor concentrate was not
      different between HA and HB groups ( P = .116). The rate of comorbidities except
      for 29 PWH having HIV who were all in the HA group was also not different between
      the 2 groups. A total of 99 (10.6%) PWH had undergone 142 TJR procedures during
      the study period. All of them had received on-demand therapy. No difference was
      found in the cumulative incidence of TJR between HA and HB ( P = .787). After
      adjusting for various confounders including age, pyogenic arthritis, and HIV
      infection, no increased risk of TJR was found in patients with HA versus Patients
      with HB (hazard ratio: 0.92, 95% confidence interval 0.54-1.58). This finding
      suggests that the rate of TJR between patients with HA and HB is not
      significantly different.

PMID- 30213204
TI  - Impact of Cardiac Risk Factors in the Postsurgical Outcomes of Patients With
      Cleft Palate: Analysis of the 2012-2014 NSQIP Database.
AB  - OBJECTIVE: To assess the risk of complication in patients undergoing cleft palate
      repair with congenital cardiac comorbidities in a large, national cohort. DESIGN:
      Retrospective review. PATIENTS/SETTING: Using the 2012-2014 National Surgical
      Quality Improvement Program (NSQIP) Pediatric database, patients undergoing cleft
      palate repair were selected for analysis. Patients with cleft palate repairs were
      stratified based on the presence or absence congenital cardiac comorbidities.
      Univariate and stepwise forward logistic regression were conducted. MAIN OUTCOME
      MEASURES: It is hypothesized that risk of postoperative adverse events in
      patients with congenital cardiac comorbidities is higher than in patients without
      cardiac disease. RESULTS: Nationally, between 2012 and 2014, 3240 patients
      underwent cleft palate repair, 422 (13.0%) with cardiac disease, and 2818 (87.0%)
      without cardiac disease. Patients with cardiac disease were smaller (10.5 [6.6]
      kg vs 11.6 [8.6] kg, P < .01) and more likely to be premature (4.6% vs 13.0%, P <
      .01) compared to those without cardiac disease. Postoperatively, patients with
      cardiac conditions were more likely to experience an adverse event (8.8% vs 4.2%,
      P < .01). Specifically, they were more likely to experience reintubation (1.7% vs
      0.4%, P < .01), reoperation (2.1% vs 0.6%, P < .01), and longer length of stay
      (2.7 [7.0] vs 1.6 [2.8] days, P < .01). Rates of surgical site infection and
      dehiscence were not different. CONCLUSIONS: Cleft palate repair in patients with
      concurrent congenital cardiac defects is a safe procedure but carries elevated
      risk in the postoperative period as demonstrated in this analysis of the NSQIP
      Pediatric database. Technical risks are equivalent. Additional anesthesia and
      surgical awareness of these potential complications is essential to minimize
      perianesthesia risks.

PMID- 30213205
TI  - What the doctor doesn't know: Discarded patient knowledge of older adults with
      multimorbidity.
AB  - Objectives Adherence to treatment has proven to require the involvement of
      patients in treatment and care planning. This process involves incorporating
      patient knowledge, or knowledge about the patients' everyday life, into the
      clinical encounter. This article explores the disclosure practices of such
      knowledge from older adults with multimorbidity. Methods This was an 18-month
      qualitative study among 14 older adults with multimorbidity living in Denmark. A
      thematic analysis was applied, focusing on perceptions of patient knowledge and
      disclosure practices among the participating patients. Results Older adults with
      multimorbidity have various reasons for not disclosing personal knowledge. The
      results present three different domains of what we termed discarded patient
      knowledge: (1) knowledge that had no direct biomedical relevance from
      participants' perspective; (2) knowledge considered too private; and (3)
      knowledge assumed to position one as inferior. Discussion The participants made
      judgments on what they believed was welcome in the clinical encounter, framing
      their knowledge within the purview of biomedicine. Participants' disclosure
      practices showed that personal knowledge is sometimes not recognized as important
      for health and care by participants themselves. Knowledge that could have
      influenced practitioners' understanding of the problem and provided different
      solutions, is argued to be discarded patient knowledge.

PMID- 30213206
TI  - Regarding Maxillary Impaction for the Treatment of Labial Incompetence in Mobius
      Syndrome.

PMID- 30213207
TI  - Detection of pathogenic Leptospira in ornamental water fountains from urban sites
      in Cali, Colombia.
AB  - Leptospirosis is a disease endemic to both rural and urban areas of tropical
      countries and resource-poor communities. Little information is available on the
      presence of Leptospira spp. in urban water sources. A study was conducted to
      detect pathogenic Leptospira in ornamental water fountains in Cali, Colombia.
      Twenty-seven water fountains were tested for pathogenic Leptospira using a
      multiplex PCR assay targeting the secY and the flaB genes. Pathogenic Leptospira
      was confirmed in 11 (41%) ornamental water fountains. Plazas, building exteriors,
      and sidewalks presented the highest proportion (67%) of pathogenic Leptospira
      positive water fountains. Urban ornamental water fountains might be sources of
      pathogenic Leptospira and might pose a risk to humans who come into close
      contact, although relevance from a public health perspective is yet to be
      established.

PMID- 30213209
TI  - Design of Ciprofloxacin-Loaded Nano-and Microcomposite Particles for Dry Powder
      Inhaler Formulations: Preparation, Invitro Characterization and Antimicrobial
      Efficacy.
AB  - In this study, ciprofloxacin hydrochloride (CIP)-loaded poly-epsilon-caprolactone
      (PCL) nanoparticles were prepared for pulmonary administration. CIP-loaded PCL
      nanoparticles were prepared by solid-in-oil-in-water (s/o/w) emulsion solvent
      evaporation method and the effects of various formulation parameters on the
      physicochemical properties of the nanoparticles were investigated. PCL
      nanoparticles showed spherical shapes with particle sizes around 143-489 nm.
      Encapsulation efficiency was found to be very low because of water-solubility
      properties of CIP. However, surface modification of nanoparticles with chitosan
      caused an increase in the encapsulation efficiency of nanoparticles. At drug
      release study, CIP-loaded PCL nanoparticles showed initial burst effect for 4 h
      and then continuously released for 72 h. Nanocomposite microparticles containing
      CIP-loaded PCL nanoparticles were prepared freeze-drying method and mannitol was
      used as carrier material. Tapped density and MMADt results show that
      nanocomposite microparticles have suitable aerodynamic properties for pulmonary
      administration. Antimicrobial efficacy investigations showed that CIP
      encapsulated PCL nanoparticles and nanocomposite microparticles inhibited the
      growth of bacteria. Also when the antimicrobial activity of the nanoparticles at
      the beginning and at the sixth month was examined, it was found that the
      structure of the particulate system was still preserved. These results indicated
      that nanocomposite microparticles containing CIP-loaded PCL nanoparticles can be
      used for pulmonary delivery.

PMID- 30213208
TI  - Tricyclic Antidepressants Modulate Stressed Mitochondria in Glioblastoma
      Multiforme Cells.
AB  - : A common feature of solid tumors, including glioblastoma multiforme (GBM), is
      mitochondrial dysfunction. However, it is reported that the current standard of
      anti-GBM therapies may potentiate mitochondrial damage and, in effect, support
      the aggressive character of cancer. As mitochondria are implicated in the
      modulation of cellular drug sensitivity and chemoresistance mechanisms,
      activation-stressed mitochondria in GBM cells may represent a new target for anti
      GBM therapy that is nontoxic for normal cells. METHODS: As mitochondria are
      possible targets for antidepressant drugs used as adjuvant therapy in patients
      with GBM, we examined their influence on mitochondrial volume and activity,
      reactive oxygen species level, extracellular lactate concentration, and p65 NF
      kappaB gene expression in GBM cells. RESULTS: Our investigation showed, for the
      first time, that tricyclic antidepressants, imipramine and amitriptyline,
      partially reverse GBM abnormalities. CONCLUSION: In the light of reported
      studies, the mitochondrial disturbance observed in glioma cells is a dynamic
      process that can be reversed or silenced. Moreover, imipramine and amitriptyline
      are attractive cellular metabolic modulators and can potentially be used to
      restoring a proper function of mitochondria in GBM cells.

PMID- 30213210
TI  - Heme oxygenase-1 inhibits neointimal hyperplasia in rat by histone deacetylase 2.
AB  - It has been reported that heme oxygenase-1 (Hmox1) induction attenuates
      neointimal thickening. Here we further investigated the potential mechanisms
      regulating this important pathological process. We revealed that histone
      deacetylase 2 (HDAC2) was induced following Hmox1 induction under 1% oxygen
      treatment and this induction was attenuated after the treatment of siRNA against
      Hmox1. Interestingly, this HDAC2 induction was dependent on Hmox1 protein as well
      as its enzymatic activity, and was regulated by carbon monoxide released from
      heme degradation. Furthermore, histone deacetylase inhibitor, trichostatin A,
      successfully abrogated the inhibitory effects of vascular smooth muscle migration
      and proliferation by Hmox1 induction in vitro. In a rat carotid balloon injury
      model, similar results were observed by measuring neointimal thickening. As such,
      we concluded that Hmox1 inhibits neointimal hyperplasia via HDAC2 in rats.

PMID- 30213211
TI  - The Information for the Dosing of Medicinal Products in Different Age Intervals
      Is Ambiguous.
AB  - OBJECTIVES: Information on the use of medicinal products should be particularly
      clear and un-ambiguous, including the information on dosing for children. Age
      groups of children in patient information leaflets are sometimes described with a
      "gap" (eg, 2-4 years, 5-12 years) or without a gap (2-4 years, 4-12 years). The
      first style is based on the view that person's age is a discrete variable and the
      second style is based on continuous understanding of person's age. The aim of
      this 3-language study was to test if these 2 styles are comprehensive. METHODS:
      We presented a dosing chapter from patient information leaflet to 274 volunteers
      and asked them what dose they would use for a child whose age is on the border
      between the two age intervals. RESULTS: We found that all commonly used styles
      are ambiguous. On average, 10% to 20% of people understand the instructions
      differently than the majority. CONCLUSIONS: A need exists to develop a new,
      unambiguous style to present this information and prevent suboptimal dosing of
      drug with a lack of efficacy or additional risks of adverse effects.

PMID- 30213213
TI  - A Message from the Editor-in-Chief.

PMID- 30213212
TI  - Triple antithrombotic therapy in patients with atrial fibrillation undergoing
      PCI: current evidence and practice.
AB  - INTRODUCTION: Patients with atrial fibrillation taking oral anticoagulation and
      undergoing percutaneous coronary intervention with stent insertion are
      recommended to receive antithrombotic therapy with aspirin and P2Y12 receptor
      antagonist. This combinatory regime encompasses triple therapy (TT). Although TT
      reduces the risk of ischemic events such as stroke and stent thrombosis, it is
      associated with an increased bleeding risk. Areas covered: The efficacy and
      safety profile of TT is uncertain with undetermined optimal duration and
      therapeutic combination. This review summarizes relevant trials evaluating TTs
      application and introduces exploration of duration and dosage in addition to
      other contributory factors including stent type and choice of antithrombotic
      agents. Expert commentary: TT has shown to be effective for reduction of ischemic
      risk. However, trials have failed to demonstrate the regime's superiority in
      efficacy over alternatives such as dual therapy (single antiplatelet plus
      anticoagulant) and continue to denote an increased bleeding risk. Further
      research driven by a balance between thromboembolic and bleeding end points is
      required to demonstrate TTs potential beneficence, along with optimal duration
      identification and antithrombotic choice. Individualized patient risk
      stratification, along with risk factor optimization should also be incorporated.

PMID- 30213214
TI  - The Sensitivity of Impact Estimates to Data Sources Used: Analysis From an Access
      to Postsecondary Education Experiment.
AB  - BACKGROUND: This article reports on the Future to Discover Project-a Canadian
      randomized controlled trial of two high school interventions-where data on key
      postsecondary enrollment outcomes were collected for two phases. During the
      initial phase, outcomes were recorded from administrative data and follow-up
      surveys. During the later phase, data came from administrative records only.
      OBJECTIVES: The article provides analyses that are informative about the
      consequences of a change from administrative-only data to survey-only data (and
      vice versa) for the estimation of impacts. RESULTS: The change from
      administrative-only to survey-only data tended to produce apparent drops in
      postsecondary enrollment rates that varied by subgroup and education outcome.
      Nonetheless, levels and significance of impact with respect to postsecondary
      enrollment remained relatively stable. CONCLUSIONS: The findings of the article
      provide evidence that estimating education program impacts in the context of a
      randomized experiment can be relatively robust to the data sources chosen. They
      suggest that internal validity and conclusions for policy need not be affected by
      changing data sources even when the change produces marked changes in levels of
      the outcome of interest observed.

PMID- 30213215
TI  - Hand strength and dexterity in patients with Prader-Willi syndrome: a pilot
      intervention study.
AB  - OBJECTIVE: The study aim was to examine the hand function (hand strength and
      dexterity) and intervention effects of training in adults with Prader-Willi
      syndrome (PWS). METHODS: Six adults with PWS (two females; mean age 26.14 years)
      underwent hand muscle strength and dexterity training for 3 months (2 hours per
      week). The following hand function tests were performed pre- and post
      intervention: (1) hand grip, lateral pinch, and tip pinch hand strength tests,
      (2) the Box and Block test (BBT) for gross manual dexterity and (3) the Purdue
      Pegboard test for finger dexterity. RESULTS: Before treatment, all subjects
      showed lower hand grip, lateral pinch, tip pinch strength, and poorer
      manual/finger dexterity relative to healthy adults. After training, hand function
      scores improved on many test items, but only the left hand tip pinch and the
      right hand BBT performance showed significant improvements. CONCLUSIONS: All
      subjects showed lower hand strength and poorer manual/finger dexterity compared
      with healthy adults; this should be considered during physical training programs.
      Owing to limitations in the intervention intensity and possible subject
      behavioral deficits, further research is needed to clarify the effects of this
      intervention on hand function in PWS patients.

PMID- 30213216
TI  - Rescue of four pediatric patients with severe influenza A (H3N2) in Weifang,
      China.
AB  - In this report, we summarize our experience of rescuing four children with severe
      type A H3N2 influenza from January to February 2017 in Weifang People's Hospital,
      Shandong Province, China for reference in clinical treatment. Two boys and two
      girls, ranging in age from 3 months to 6 years, with fever, cough, and asthma,
      were admitted to the pediatric intensive care unit. All children had severe
      pulmonary infection with respiratory distress. Three children had myocardial
      damage, two had liver damage, and one had encephalitis. One child had a history
      of bronchial asthma and one had severe spinal muscular atrophy. After all four
      children were admitted to the pediatric intensive care unit, they were provided
      active and effective organ function support and ventilator-assisted respiration.
      They were treated with gamma globulin, methylprednisolone, and antibiotics. Three
      children were treated with anti-influenza drugs and recovered from influenza; one
      child died even before antiviral treatment intervention on the first day.
      Definite diagnosis of the cases was through clinical manifestations, supplemented
      by laboratory tests, such as influenza virus H3N2 rapid antigen detection and
      nucleic acid detection. Early antiviral therapy, high-dose glucocorticoids and
      immunoglobulins, and systemic comprehensive rescue might be important for
      rescuing children with severe influenza A (H3N2).

PMID- 30213217
TI  - Implementation of a Direct Oral Anticoagulation Screening Service at a Large
      Academic Medical Center Provided by a Pharmacist-managed Antithrombosis Clinic as
      a Method to Expand Antithrombotic Stewardship Efforts.
AB  - BACKGROUND: How and when to monitor direct oral anticoagulants (DOACs) for safety
      and efficacy is a question many anticoagulation clinics are trying to answer. A
      pharmacist-led antithrombosis clinic (ATC) initiated a clinical service to
      provide oversight for all prescribed DOACs. OBJECTIVE: Describe the
      implementation and outcomes of a DOAC screening service. METHODS: The service was
      initiated utilizing a daily electronic prescribing report of DOAC prescriptions.
      Prescriptions were reviewed by clinical pharmacists to assess patient insurance,
      eligibility, and accuracy of prescribed doses. RESULTS: In the first year since
      service implementation in April 2016, 317 new prescriptions and 595 refill
      prescriptions were reviewed. A DOAC service pharmacist was able to reach 125
      (39.4%) of 317 patients about their new prescription and 59 (9.9%) of 595 refill
      patients to provide education and follow-up on management as needed.
      Interventions were performed for 79 (28%) of 317 new prescriptions and 86 (14.5%)
      of 595 refill prescriptions. Common interventions with new prescriptions include
      contacting the prescriber for a medication or dose change (25.4%), assistance
      with medication access (21.5%), and coordinating appropriate lab and provider
      follow up (21.5%). Common interventions with refill prescriptions include
      recommending appropriate follow-up (50%) and contacting the prescriber for
      medication or dosage change (24.4%). CONCLUSION: Implementation of a DOAC
      screening service identified and resolved dosing errors, improved medication
      access, provided patient education, and improved follow-up.

PMID- 30213218
TI  - Effects of fibrin glue as a three-dimensional scaffold in cultivated adult human
      retinal pigment epithelial cells.
AB  - This study was conducted to examine morphological, genotypic, and phenotypic
      alterations occurring in cultured adult human retinal pigment epithelial cells
      when encapsulated with different concentrations of fibrin glue. Cultivated adult
      human retinal pigment epithelial cells were encapsulated with different
      concentrations of fibrin glue, namely FG1 (42 mg/dl), FG2 (84 mg/dl), FG3 (124
      mg/dl), FG4 (210 mg/dl), followed by the evaluation of genetic and
      cytomorphological changes and protein expression. Cultured adult human retinal
      pigment epithelial cells showed dendritiform morphology during the early days of
      encapsulation with fibrin glue. Moreover, an increasing inhibitory effect on cell
      growth was observed with increasing concentrations of fibrin glue. At the
      transcriptional level, the expression of MMP2, PAX6, and ITGB1 in FG1
      encapsulated cells was significantly higher than that in other treated groups;
      however, the expression of ACTA2 was lower in all fibrin glue-encapsulated groups
      compared to that in the controls. Immunocytochemistry showed that FG2
      encapsulated cells expressed cytokeratin 8/18, RPE65, and ZO-1 proteins, but not
      PAX6. In conclusion, fibrin glue at a concentration of 84 mg/dl allows proper
      encapsulation of adult human retinal pigment epithelial cells, while preserving
      the morphometric, genotypic, and phenotypic features of the cells. This three
      dimensional biopolymer can be considered a reliable vehicle for retinal pigment
      epithelium cell transplantation in cell-based therapies.

PMID- 30213219
TI  - Association of low socioeconomic status and physician assessment of disease
      severity with oral health-related quality of life in patients with systemic
      sclerosis: a pilot study from Croatia, a country in transition.
AB  - Objective This study was performed to identify a possible association of the
      clinical parameters of systemic sclerosis (SSc) and the socioeconomic status
      (SES) with oral health-related quality of life (OHrQoL) as measured by the Oral
      Health Impact Profile 49 (OHIP 49), taking into account the effect of educational
      level (as a proxy of SES) on oral health. Methods Subjects were recruited from
      the Croatian SSc Center of Excellence cohort. Detailed dental and clinical
      examinations were performed according to standardized protocols. The associations
      of OHrQoL with disease characteristics and socioeconomic status were examined.
      Results Thirty-one consecutive patients with SSc were enrolled (29 women; mean
      age, 56.45 +/- 13.60 years). OHIP 49 scores were significantly correlated with
      disease activity and severity. Furthermore, OHrQoL was positively correlated with
      skin involvement as evaluated by the modified Rodnan skin score. Impaired OHrQoL
      was positively correlated with the severity of general, skin, gastrointestinal,
      and joint/tendon involvement. The OHIP 49 score differed between patients who
      were positive and negative for anti-topoisomerase I antibody. Higher OHIP 49
      scores were detected in patients with lower SES (primary school educational
      level). Conclusion Collaboration between rheumatologists and dental professionals
      is required to improve dental care and oral health outcomes of SSc.

PMID- 30213220
TI  - Increased circulating levels of tumor necrosis factor-like cytokine 1A and decoy
      receptor 3 correlate with SYNTAX score in patients undergoing coronary surgery.
AB  - Objective Chronic inflammation of the arteries is a critical mechanism
      responsible for coronary atherosclerosis. We aimed to determine if tumor necrosis
      factor (TNF)-like cytokine 1A (TL1A) and decoy receptor 3 (DcR3) were involved in
      promoting atherosclerosis. Methods We compared plasma levels of TL1A and DcR3 in
      patients with coronary artery disease (CAD) undergoing coronary artery bypass
      grafting (n=40) and patients without CAD group (n=37, normal coronary artery
      angiogram) by enzyme-linked immunosorbent assay. We also analyzed the correlation
      between CAD and SYNTAX scores. Results Plasma levels of TL1A and DcR3 were
      significantly higher in the CAD compared with the no-CAD group. Multivariate
      analysis showed that TL1A and DcR3 were significantly correlated with the
      presence of CAD, and receiver operating characteristic curve analysis indicated
      that both TL1A and DcR3 showed high sensitivity and specificity for diagnosing
      CAD. Furthermore, TL1A was positively and significantly correlated with SYNTAX
      score in CAD patients. Conclusions CAD patients requiring coronary artery bypass
      grafting have high circulating levels of both TL1A and DcR3, which may thus be
      useful biomarkers for diagnosing severe CAD. Furthermore, plasma levels of TL1A
      correlate with SYNTAX score, supporting its potential use as an indicator of the
      severity of CAD.

PMID- 30213221
TI  - Acute Ketamine Infusion in Rat Does Not Affect In Vivo [11C]ABP688 Binding to
      Metabotropic Glutamate Receptor Subtype 5.
AB  - Detecting changes in metabotropic glutamate receptor 5 (mGluR5) availability
      through molecular imaging with the positron emission tomography (PET) tracer
      [11C]ABP688 is valuable for studying dysfunctional glutamate transmission
      associated with neuropsychiatric disorders. Using an infusion protocol in rats,
      we visualized the acute effect of subanesthetic doses of ketamine on mGluR5 in
      rat brain. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist known
      to increase glutamate release. Imaging was performed with a high-affinity PET
      ligand [11C]ABP688, a negative allosteric modulator of mGluR5. Binding did not
      change significantly from baseline to ketamine in any region, thereby confirming
      previous literature with other NMDA receptor antagonists in rodents. Hence, in
      rats, we could not reproduce the findings in a human setup showing significant
      decreases in the [11C]ABP688 binding after a ketamine bolus followed by ketamine
      infusion. Species differences may have contributed to the different findings in
      the present study of rats. In conclusion, we could not confirm in rats that
      endogenous glutamate increases by ketamine infusion are reflected in [11C]ABP688
      binding decreases as was previously shown for humans.

PMID- 30213223
TI  - "Real-World" Application of Thrombolysis in Cardiac Arrest.
AB  - BACKGROUND: Current guidelines recommend consideration of thrombosis as a
      reversible cause of cardiac arrest. The use of thrombolytic therapy during
      cardiac arrest, however, is controversial. OBJECTIVE: We sought to characterize
      the use of thrombolytic therapy during cardiac arrest and to evaluate the rate of
      return of spontaneous circulation (ROSC) in a "real-word" setting. METHODS: A
      single-center, retrospective, cohort study of adult patients who received
      alteplase during cardiac arrest between 2010 and 2015 were performed at a
      tertiary academic medical center. RESULTS: Twenty-six patients were identified.
      Patients were predominantly male (65%) and Caucasian (89%) and were a median age
      of 64 years. Five patients had a history of preexisting venous thromboembolism,
      and eight patients were receiving systemic anticoagulation. Pulmonary embolism
      was confirmed prior to the administration of alteplase in 5 patients. The median
      dose of alteplase administered was 100 mg. ROSC was achieved in 65% of patients,
      2 of whom survived to hospital discharge. Both surviving patients experienced a
      bleeding event. CONCLUSION: In a single center's experience, thrombolytic therapy
      is used infrequently for the management of cardiac arrest. Thrombolysis during
      cardiac arrest should be considered on a case-by-case basis and should be
      utilized only when there is a high suspicion for pulmonary embolism as the cause
      of arrest and when thrombolytic therapy is readily available.

PMID- 30213224
TI  - The Notch Family Transcription Factor, RBPJkappa, Modulates Glucose Transporter
      and Ovarian Steroid Hormone Receptor Expression During Decidualization.
AB  - During decidualization, endometrial stromal cells differentiate into a secretory
      phenotype to modulate the uterine microenvironment and promote embryo
      implantation. This highly metabolic process relies on ovarian steroid receptors
      and glucose transporters. Canonical Notch signaling is mediated by the
      transcription factor Recombination Signal Binding Protein for Immunoglobulin
      Kappa J Region (RBPJ). Loss of RBPJ in the mouse uterus ( Pgrcre/+Rbpjflox/flox;
      Rbpj c-KO) results in subfertility in part due to an abnormal uterine-embryonic
      axis during implantation and, as described herein, decidualization failure.
      Induced in vivo decidualization in Rbpj c-KO mice was impaired with the
      downregulation of decidual markers and decreased progesterone receptor (Pgr)
      signaling. Consistent with in vivo mouse data, RBPJ knockdown during in vitro
      Human uterine fibroblast (HuF) cell decidualization results in the reduced
      expression of decidual marker genes along with PGR. Expression of the glucose
      transporter, SLC2A1, was decreased in the RBPJ-silenced HuF cells, which
      corresponded to decreased Slc2a1 in the secondary decidual zone of Rbpj c-KO
      mouse uteri. Exogenous administration of pyruvate, which bypasses the need for
      glucose, rescues PRL expression in RBPJ-deficient HuF cells. In summary, Notch
      signaling through RBPJ controls both ovarian steroid receptor PGR and glucose
      transporter SLC2A1 expression during decidualization, and this dysregulation
      likely contributes to embryo implantation failure.

PMID- 30213226
TI  - Spleen thickness can predict significant liver pathology in patients with chronic
      hepatitis B with persistently normal alanine aminotransferase or minimally raised
      alanine aminotransferase: a retrospective study.
AB  - Objective Liver biopsy is the gold standard test for assessment of liver
      pathology. This study was performed to assess the predictive value of spleen
      thickness for liver pathology and the role of routine follow-up procedures in
      significant liver pathology for patients with chronic hepatitis B (CHB) with
      persistently normal alanine aminotransferase (PNALT) or minimally raised alanine
      aminotransferase (ALT). Methods Patients with CHB who underwent percutaneous
      liver biopsy were retrospectively reviewed. The relationship of liver pathology
      with age, ALT, hepatitis B e-antigen, and spleen thickness was statistically
      analyzed, and the predictive accuracy of spleen thickness was evaluated. Results
      In total, 80.65% of patients had significant necroinflammation and/or fibrosis.
      Nearly 60% of patients had splenomegaly, of which 89.12% had a histopathological
      grade of >=G2 and/or S2. Spleen thickness was predictive of liver pathology, and
      significant histological findings increased as the hepatitis B virus (HBV) DNA
      level increased. Conclusions Spleen thickness is an effective predictor of liver
      pathology in patients with PNALT or minimally raised ALT. Additionally, the
      prevalence of significant histological findings tended to increase as the HBV DNA
      level increased. Patients with CHB and splenomegaly and a high HBV DNA level
      should be treated early with antivirals to improve liver pathology.

PMID- 30213227
TI  - Kinematic sequence patterns in the overhead baseball pitch.
AB  - Conceptually, an efficient baseball pitch demonstrates a proximal-to-distal
      transfer of segmental angular velocity. Such a timing pattern (or kinematic
      sequence) reduces stress on musculoskeletal structures of the throwing arm and
      maximises ball velocity. We evaluated the variability of kinematic sequences in
      208 baseball pitches. 3D biomechanical pitch analyses were performed on 8-10
      fastball pitches from 22 baseball pitchers (5 high school, 11 collegiate and 6
      professional). The kinematic sequence patterns - time of peak angular velocity of
      five body segments: pelvis, trunk, arm, forearm and hand - were measured. None of
      the pitches analysed demonstrated an entirely proximal-to-distal kinematic
      sequence. Fourteen different kinematic sequence patterns were demonstrated, with
      the most prevalent sequence being pelvis -> trunk -> arm -> hand -> forearm.
      Fewer than 10% of the pitchers performed only one kinematic sequence pattern
      across the sampled pitches. The variability of the kinematic sequence was similar
      in high-school pitchers and professionals. Previous studies report that deviation
      from the proximal-to-distal kinematic sequence is associated with increased
      injury risk. As a method of evaluating the efficient transfer of energy to the
      hand, the kinematic sequence may provide insight to injury risk in the future.
      The ideal kinematic sequence and ideal variability of the sequence when throwing
      have yet to be determined.

PMID- 30213225
TI  - Added value of contrast echocardiography in characterization of nonischemic
      cardiomyopathy.
AB  - Nonischemic cardiomyopathy (NICM) is a group of noncoronary heterogonous
      myocardial diseases. The heterogonous nature of NICM has impeded its diagnosis.
      In the present case series, we demonstrate the added value of using contrast
      echocardiography in the characterization of NICM. Two patients of advanced age
      were admitted for possible acute coronary syndrome, which was subsequently
      excluded by coronary angiography. Conventional and contrast echocardiography
      revealed characteristic structural and dynamic features of the left ventricle
      that were compatible with two distinct NICM diseases: stress-induced
      cardiomyopathy and noncompaction of the ventricular myocardium. Contrast
      echocardiography characterizes the cardiac structure and allows for real-time
      assessment of myocardial motion and perfusion. It may help to distinguish
      diseases with different etiologies.

PMID- 30213222
TI  - From Micro- to Nano-Multifunctional Theranostic Platform: Effective Ultrasound
      Imaging Is Not Just a Matter of Scale.
AB  - Ultrasound Contrast Agents (UCAs) consisting of gas-filled-coated Microbubbles
      (MBs) with diameters between 1 and 10 um have been used for a number of decades
      in diagnostic imaging. In recent years, submicron contrast agents have proven to
      be a viable alternative to MBs for ultrasound (US)-based applications for their
      capability to extravasate and accumulate in the tumor tissue via the enhanced
      permeability and retention effect. After a short overview of the more recent
      approaches to ultrasound-mediated imaging and therapeutics at the nanoscale,
      phase-change contrast agents (PCCAs), which can be phase-transitioned into highly
      echogenic MBs by means of US, are here presented. The phenomenon of acoustic
      droplet vaporization (ADV) to produce bubbles is widely investigated for both
      imaging and therapeutic applications to develop promising theranostic platforms.

PMID- 30213228
TI  - Post-Renal Transplantation Outcomes in Elderly Patients Compared to Younger
      Patients in the Setting of Early Steroid Withdrawal.
AB  - BACKGROUND:: Previous studies reported improved outcomes for renal recipients
      undergoing early steroid withdrawal (ESW), with significantly lower rates of new
      onset diabetes, cytomegalovirus (CMV), and malignancy. As renal transplants in
      older adults has increased, studies have shown similar outcomes between elderly
      and younger patients. We aim to evaluate post-renal transplantation outcomes in
      elderly patients compared to younger patients who have undergone ESW. METHODS:: A
      retrospective analysis of adults who received transplants between January 2004
      and December 2014 and received either basiliximab or antithymocyte globulin for
      induction, underwent ESW, and received tacrolimus and mycophenolate for
      maintenance. Patients were stratified based on age (>=60 vs <60). The 1-year
      primary end point was a composite of patient survival, graft survival, biopsy
      proven acute rejection, and serum creatinine. The secondary outcomes included
      renal function, the incidence of opportunistic infections, malignancies,
      diabetes, and cardiovascular complications. Cox regression was used to evaluate
      variables that may affect rejection. RESULTS:: The sample included 292 patients;
      72 were elderly individuals and 220 were younger adults. No significant
      differences were found in the primary end point or incidence of CMV, BK virus, or
      malignancy ( P = 1.0, .82, and .06, respectively). The use of blood pressure
      medications and the need for lipid-lowering agents were significantly higher in
      elderly patients at last follow-up. Diabetes was more common in elderly patients
      (15.2% vs 8.41%, P = .11). The induction agent used did not show any significant
      effect on rejection risk. CONCLUSION:: We report similar outcomes in elderly
      patients compared to younger patients in the setting of ESW.

PMID- 30213229
TI  - The Effect of Assisted Hatching on Live Birth Rate Following Fresh Embryo
      Transfer in Advanced Maternal Age.
AB  - OBJECTIVE: Assisted hatching (AH) was introduced 3 decades ago as an adjunct
      method to in vitro fertilization (IVF) and embryo transfer (ET) to improve embryo
      implantation rate. Limited data are available on the effect of AH on live birth
      rate (LBR) in advanced maternal age. The objective of this study is to
      investigate the effect of AH on LBR in women aged 40 years and older. MATERIALS
      AND METHODS: A retrospective study conducted at a single academic reproductive
      center. Women aged >=40 years, who were undergoing their first IVF cycle were
      included. Laser-assisted hatching was the method used for AH and single or double
      embryos were transferred. Embryo transfer was performed at the cleavage or
      blastocyst stage. Separate analysis was performed on each ET stage. Live birth
      rate was the primary outcome. RESULTS: A total of 892 patients were included. Of
      these, 681 women underwent cleavage ET and 211 underwent blastocyst ET. The
      clinical pregnancy rate in the entire group was 15.3% and the LBR was 10.2%.
      Baseline and cycle parameters between the AH group and the control group were
      comparable. Assisted hatching in the cleavage stage was associated with lower
      clinical pregnancy rate (odds ratio [OR], 0.52; confidence interval [CI], 0.31
      0.86; P = .012) and lower LBR (OR, 0.36; CI, 0.19-0.68; P = .001). Assisted
      hatching did not have any effect on outcomes in blastocyst ET. CONCLUSION:
      Assisted hatching does not improve the reproductive outcomes in advanced maternal
      age. Performing routine AH for the sole indication of advanced maternal age is
      not clinically justified.

PMID- 30213232
TI  - Age, Cohort, and Social Change: Parental and Spousal Education and White Women's
      Health Limitations From 1967 to 2012.
AB  - A large body of research finds that the association between educational
      attainment and health is at historic highs for White women. Rapid changes in
      labor force participation, access to high-paying jobs, and gender attitudes have
      radically altered the meaning of education for women's lives and their dependence
      on the socioeconomic attainments of their families. Drawing on three nationally
      representative longitudinal surveys conducted from 1967 to 2012, this study
      examines how personal, parental, and spousal attainments contribute to the
      widening education gap in health for successive cohorts of White women ( N =
      8,405). Overall, the health of women did not change substantially across cohorts,
      but results did uncover cohort differences among low-educated women that were
      linked to parental and spousal educational attainments and personal earnings.
      These findings confirm growing educational inequalities in health and demonstrate
      the importance of historical context and family attainments when examining cohort
      variation in the education-health relationship.

PMID- 30213230
TI  - The Binding of BF-227-Like Benzoxazoles to Human alpha-Synuclein and Amyloid beta
      Peptide Fibrils.
AB  - Development of an alpha-synuclein (alpha-Syn) positron emission tomography agent
      for the diagnosis and evaluation of Parkinson disease therapy is a key goal of
      neurodegenerative disease research. BF-227 has been described as an alpha-Syn
      binder and hence was employed as a lead to generate a library of alpha-Syn
      binding compounds. [3H]BF-227 bound to alpha-Syn and amyloid beta peptide (Abeta)
      fibrils with affinities (KD) of 46.0 nM and 15.7 nM, respectively. Affinities of
      BF-227-like compounds (expressed as Ki) for alpha-Syn and Abeta fibrils were
      determined, along with 5 reference compounds (flutafuranol, flutemetamol,
      florbetapir, BF-227, and PiB). Selectivity for alpha-Syn binding, defined as the
      Ki(Abeta)/Ki(alpha-Syn) ratio, was 0.23 for BF-227. A similar or lower ratio was
      measured for analogues decorated with alkyl or oxyethylene chains attached to the
      oxygen at the 6 position of BF-227, suggesting a lack of involvement of the side
      chain in fibril binding. BF-227-like iodobenzoxazoles had lower affinities and
      poor alpha-Syn selectivity. However, BF-227-like fluorobenzoxazoles had improved
      alpha-Syn selectively having Ki(Abeta)/Ki(alpha-Syn) ranging from 2.2 to 5.1 with
      appreciable fibril affinity, although not sufficient to warrant further
      investigation. Compounds based on fluorobenzoxazoles might offer an approach to
      obtaining an alpha-Syn imaging agent with an appropriate affinity and
      selectivity.

PMID- 30213231
TI  - Ectopic transglutaminase 1 and 3 expression accelerating keratinization in oral
      lichen planus.
AB  - OBJECTIVE: Oral lichen planus (OLP) characterized by interface mucositis
      frequently shows hyper-keratinization. To clarify mechanisms of excess
      keratinization, we investigated key molecules for cornified cell envelope (CE).
      METHODS: Involucrin (IVL), loricrin (LOR), transglutaminase 1 (TGase 1) and
      transglutaminase 3 (TGase 3) were immunohistochemically examined in 20 specimens
      of OLP; five specimens of buccal mucosa served as controls. Subsequently, the
      data were statistically analyzed. RESULTS: IVL in OLP was localized in the cell
      membrane, in contrast to its localization in the cytoplasm in controls. No
      positive reaction indicative of LOR was noted in any specimens. Although the
      TGase 1 localization in controls was restricted to the upper three-quarters of
      the membrane, the localization in OLP was in both membrane and in the cytoplasm
      of full thickness mucosal layers. The TGase 3 localization pattern was
      dramatically altered from cytoplasmic to membranous in OLP. CONCLUSION: Our data
      suggest that aberrant TGase 1 and TGase 3 localization and distribution are
      closely related to hyper-keratinization in OLP. This is the first report of
      ectopic transglutaminase localization in OLP.

PMID- 30213233
TI  - Reducing anthracycline-induced cardiotoxicity through pharmacogenetics.

PMID- 30213234
TI  - Renal Allograft Torsion Following Simultaneous Pancreas Kidney Transplant Should
      Be Suspected With Sustained Kidney Injury With Normal Pancreas Function.

PMID- 30213235
TI  - Diagnostic Criteria for Somatosensory Tinnitus: A Delphi Process and Face-to-Face
      Meeting to Establish Consensus.
AB  - Since somatic or somatosensory tinnitus (ST) was first described as a subtype of
      subjective tinnitus, where altered somatosensory afference from the cervical
      spine or temporomandibular area causes or changes a patient's tinnitus
      perception, several studies in humans and animals have provided a
      neurophysiological explanation for this type of tinnitus. Due to a lack of
      unambiguous clinical tests, many authors and clinicians use their own criteria
      for diagnosing ST. This resulted in large differences in prevalence figures in
      different studies and limits the comparison of clinical trials on ST treatment.
      This study aimed to reach an international consensus on diagnostic criteria for
      ST among experts, scientists and clinicians using a Delphi survey and face-to
      face consensus meeting strategy. Following recommended procedures to gain expert
      consensus, a two-round Delphi survey was delivered online, followed by an in
      person consensus meeting. Experts agreed upon a set of criteria that strongly
      suggest ST. These criteria comprise items on somatosensory modulation, specific
      tinnitus characteristics, and symptoms that can accompany the tinnitus. None of
      these criteria have to be present in every single patient with ST, but in case
      they are present, they strongly suggest the presence of ST. Because of the
      international nature of the survey, we expect these criteria to gain wide
      acceptance in the research field and to serve as a guideline for clinicians
      across all disciplines. Criteria developed in this consensus paper should now
      allow further investigation of the extent of somatosensory influence in
      individual tinnitus patients and tinnitus populations.

PMID- 30213236
TI  - SRS in Combination With Ipilimumab: A Promising New Dimension for Treating
      Melanoma Brain Metastases.
AB  - Stereotactic radiosurgery provides effective local control, but high recurrence
      rate are observed while ipilimumab have shown promising improvements in survival
      in the treatment of melanoma brain metastases. This meta-analysis was done to
      review the clinical evidence regarding the combination of stereotactic
      radiosurgery and ipilimumab in the treatment of brain metastases from melanoma.
      Comprehensive research of the electronic databases (PubMed and Cochrane Library)
      was carried out in April 2017. Different combination of MESH headings and words
      were used. Review Manager was used to analyze the outcome data of interest.
      According to heterogeneity, fixed effects model or random effects model was
      adapted. Six retrospective studies comparing stereotactic radiosurgery plus
      ipilimumab with stereotactic radiosurgery alone were found. Total of 411
      participants were included in this meta-analysis. Of that, 128 patients had
      received stereotactic radiosurgery + ipilimumab, while 283 patients had received
      stereotactic radiosurgery only. Stereotactic radiosurgery plus ipilimumab
      significantly improved survival when compared to stereotactic radiosurgery alone
      (hazard ratio: 0.74 [95% confidence interval: 0.56-0.99, P = .04]), with no
      significant increase in the incidence of adverse events (odds ratio 0.57 [95%
      confidence interval: 0.28-1.17, P = .12]). Stereotactic radiosurgery with
      ipilimumab is safe and effective treatment option and can be recommended for the
      treatment of brain metastases in patients with melanoma.

PMID- 30213238
TI  - Neurobehavioral disability in stroke patients during subacute inpatient
      rehabilitation: prevalence and biopsychosocial associations.
AB  - BACKGROUND AND OBJECTIVES: There are scarce data on post-stroke neurobehavioral
      disability (NBD). The aim of this study was to identify the prevalence of NBD in
      a subacute inpatient stroke population and examine potential associations with
      demographic, stroke-related, functional and psychosocial variables. METHODS: 82
      survivors of stroke were consecutively recruited during their inpatient
      rehabilitation admission. Nursing staff rated NBD in patients using the St
      Andrews -Swansea Neurobehavioral Outcome Scale (SASNOS). Measures of patient
      functional independence (FIM), cognition (MoCA), and mood symptoms (HADS) were
      collected in addition to nursing reports of whether observed NBD negatively
      impacted on the patient or those around them. RESULTS: NBD relating to
      interpersonal relationships (44.4% of participants) and cognition (52.4%) were
      highly prevalent within the sample while NBD relating to inhibition (1.2%),
      aggression (3.6%), and communication (2.5%) were relatively rare. Presence of NBD
      was significantly associated with reduced functional independence (rs=0.39, p <
      0.01) and associated with trends in cognitive impairment (rs=0.29, p = 0.03),
      increased anxiety (rs=-0.43, p = 0.02) and depressive symptoms (rs=-0.43, p =
      0.02). Presence of NBD was significantly correlated with negative impact to the
      patient and those around them across all SASNOS domains (rs range 0.42 - 0.45,
      all p <= 0.01). CONCLUSIONS: NBD is common within a subacute stroke inpatient
      population, particularly interpersonal and cognitive difficulties and preliminary
      analyses indicate associations with reduced functional ability, cognition and
      mood. There is a need to provide education and support to clinicians to
      facilitate routine assessment and management of NBD following stroke.

PMID- 30213237
TI  - Excessive release of endogenous neuropeptide Y into cerebrospinal fluid after
      treatment of spontaneous subarachnoid haemorrhage and its possible impact on self
      reported neuropsychological performance - results of a prospective clinical pilot
      study on good-grade patients.
AB  - OBJECTIVES: Neuropsychological dysfunction after treatment of spontaneous
      subarachnoid haemorrhage (sSAH) is common but underreported. The vasoconstrictor
      neuropeptide Y (NPY) is excessively released after sSAH and in psychiatric
      disorders. We prospectively analysed the treatment-specific differences in the
      secretion of endogenous cerebrospinal fluid (CSF) NPY during the acute stage
      after sSAH and its impact on cognitive processing. METHODS: A total of 26
      consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were
      enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6
      microsurgery, and n = 6 patients with perimesencephalic SAH received standardized
      intensive medical care. Ventricular CSF was drawn daily from day 1-10. CSF NPY
      levels were determined with competitive enzyme immunoassay. All patients
      underwent neuropsychological self-report assessment [36-Item Short Form Health
      Survey (SF-36) and ICD-10-Symptom-Rating questionnaire (ISR)] after the onset of
      sSAH (day 11-35; t1) and at the 6-month follow-up (t2). RESULTS: At t1, increased
      mean levels of NPY in CSF significantly correlated with impaired performance in
      most ISR scores (ISR total p = .018, depression p = .035, anxiety p = .008,
      nutrition disorder p = .047, supplementary items p = .038) and in several
      psychological SF-36 items (vitality p = .019, general mental health p = .001,
      mental component summary p = .025). DISCUSSION: To the best of our knowledge,
      this study is the first to correlate the levels of endogenous NPY in
      supratentorial CSF with cognitive outcome in good-grade sSAH patients. Excessive
      NPY release into CSF may have a short-term influence on the pathogenesis of
      neuropsychological deficits. The impact of cerebrovascular manipulation on NPY
      release has to be further elucidated. ABBREVIATIONS: ANOVA: analysis of variance;
      aSAH: aneurysmal subarachnoid haemorrhage; AUC: area under the curve; CBF:
      cerebral blood flow; CSF: cerebrospinal fluid; CT (scan): computed tomography
      (scan); CV: cerebral vasospasm; DIND: delayed ischemic neurological deficit; DSA:
      digital subtraction angiography; EIA: enzyme immunoassay; EV: endovascular
      aneurysm occlusion; EVD: external ventricular drainage; FU: 6-month follow-up;
      GCS: Glasgow Coma Scale; Ghp: general health perceptions; GOS: Glasgow Outcome
      Scale; h: hour/s; HH: Hunt and Hess; ICU: intensive care unit; ISR: ICD-10
      Symptom-Rating questionnaire; MCS: mental component summary; Mhi: general mental
      health; min: minute/s; min-max: minimum - maximum; ml: millilitre; mRS: modified
      Ranking Scale; MS: microsurgical clipping, microsurgical aneurysm occlusion; ng:
      nanograms; no. [n]: number; NPY: Neuropeptide Y; p: p value; Pain: bodily pain;
      PCS: physical component summary; Pfi: physical functioning; pSAH:
      perimesencephalic subarachnoid haemorrhage; PTSD: posttraumatic stress disorder;
      QoL: quality of life; Rawhtran: health transition item; Rolem: role limitations
      because of emotional problems; Rolph: role limitations due to physical health
      problems; SAH: subarachnoid haemorrhage; SD: standard deviation; SF-36: 36-Item
      Short Form Health Survey; Social: social functioning; sSAH: spontaneous
      subarachnoid haemorrhage; TCD: trans-cranial Doppler ultrasound; (test) t1: test
      in the sub-acute phase after the onset of bleeding (between day 11 and 35 after
      subarachnoid haemorrhage); (test) t2: test in the short-term (chronic phase)
      after treatment at 6-month follow-up; test t1 - t2: intergroup development from
      t1 to t2; Vital: vitality; vs: versus.

PMID- 30213239
TI  - Trypsin inhibition by Ligupurpuroside B as studied using spectroscopic, CD, and
      molecular docking techniques.
AB  - It is well known that Ligupurpuroside B is a water-soluble polyphenolic compound
      and used to brew bitter tea with antioxidant activities. It acted as a stimulant
      to the central nervous system and a diuretic (increase the excretion of urine),
      was used to treat painful throat and high blood pressure, and also exerted weight
      loss function. In this regard, a detailed investigation on the mechanism of
      interaction between Ligupurpuroside B and trypsin could be of great interest to
      know the pharmacokinetic behavior of Ligupurpuroside B and for the design of new
      analogues with effective pharmacological properties. Ligupurpuroside B
      successfully quenched the intrinsic fluorescence of trypsin via static quenching
      mechanism. The binding constants (Ka) at three temperatures (288, 298, and 308 K)
      were 1.7841 * 104, 1.6251 * 104 and 1.5483 * 104 L mol-1, respectively. Binding
      constants revealed the stronger binding interaction between Ligupurpuroside B and
      trypsin. The number of binding sites approximated to one, indicating a single
      class of binding for Ligupurpuroside B in trypsin. The enzyme activity result
      suggested that Ligupurpuroside B can inhibit trypsin activity. Thermodynamic
      results revealed that both hydrogen bonds and hydrophobic interactions play main
      roles in stabilization of Ligupurpuroside B-trypsin complex. Circular dichroism
      (CD) results showed that the conformation of trypsin changed after bound to
      ligupurpuroside B. Molecular docking indicated that Ligupurpuroside B can enter
      the hydrophobic cavity of trypsin and was located near Trp215 and Tyr228 of
      trypsin. Communicated by Ramaswamy H. Sarma.

PMID- 30213240
TI  - The effect of using the Partners for Change Outcome Management System as feedback
      tool in psychotherapy-A systematic review and meta-analysis.
AB  - OBJECTIVE: The aims of the study were to evaluate the effects of using the
      Partners for Change Outcome Management System (PCOMS) in psychotherapy and to
      explore potential moderators of the effect. METHOD: A comprehensive literature
      search including grey literature was conducted to identify controlled outcome
      studies on the PCOMS, randomized (RCTs), or non-randomized trials (N-RCT).
      RESULTS: The literature search identified 18 studies, 14 RCTs, and four N-RCTs,
      including altogether 2910 participants. The meta-analysis of all studies found a
      small overall effect of using the PCOMS on general symptoms (g  =  0.27, p  = 
      .001). The heterogeneity of the results was substantial. Moderation analyses
      revealed no effect of the PCOMS in psychiatric settings (g  =  0.10, p  =  .144),
      whereas a positive effect was found in counseling settings (g  =  0.45, p  < 
      .001), although almost all of these studies were characterized by a positive
      researcher allegiance and using the PCOMS Outcome Rating Scale (ORS) as the only
      outcome measure. CONCLUSION: The meta-analysis revealed a small overall effect of
      using the PCOMS, but no effect in psychiatric settings. The positive results in
      counseling settings might be biased due to researcher allegiance and use of the
      ORS as the only outcome measure.

PMID- 30213241
TI  - Collagen Features of Dermatofibrosarcoma Protuberans Skin Base on Multiphoton
      Microscopy.
AB  - Dermatofibrosarcoma protuberans is a rare, low-grade skin fibroblastic tumor
      which tends to recur locally due to its high misdiagnosis. Dermatofibrosarcoma
      protuberans usually spreads through the intracutaneous and subcutaneous layers
      into the deep dermis layer in which the main component is collagen. Therefore,
      alterations in collagen shape and content are important for accurate diagnosis of
      dermatofibrosarcoma protuberans. In this study, multiphoton microscopy was
      employed to observe normal human skin and dermatofibrosarcoma protuberans skin.
      Then, a centerline based on an algorithm that skeletonizes a binary image of
      fibers was applied to analyze collagen shapes in 2 types of skin. Then, collagen
      content, including intensity and density, was quantitatively obtained to
      demonstrate differences between the 2 skin types. Results indicate that collagen
      shape and density can be considered as auxiliary diagnostic parameters to improve
      the accuracy of dermatofibrosarcoma protuberans diagnosis.

PMID- 30213242
TI  - Mycotic Aortic Aneurysm and Infected Aortic Graft After Intravesical Bacillus
      Calmette-Guerin Treatment for Bladder Cancer.
AB  - Although intravesical therapy with bacillus Calmette-Guerin (BCG) has proven its
      efficiency in the treatment of early-stage bladder cancer, infectious
      complications can occur and mycotic aneurysms represent a rare but life
      threatening complication. Here, we report the case of an aortic graft infection
      in a patient with abdominal aortic aneurysm who received BCG instillations for
      the treatment of bladder cancer. Based on the current knowledge on this rare
      vascular complication, we discuss factors that may have contributed to its
      occurrence and review issues to optimize its management and early detection.

PMID- 30213243
TI  - Neuroimaging, serum biomarkers, and patient characteristics as predictors of
      upper limb functioning 12 weeks after acute stroke: an observational, prospective
      study.
AB  - OBJECTIVE: To evaluate the potential of neuroimaging, serum biomarkers, stroke
      etiology, and clinical characteristics as predictors of upper limb functioning 12
      weeks after stroke. METHODS: This was a prospective, observational study of
      patients (18-85 years-old) hospitalized due to acute ischemic stroke in the
      territory of the middle cerebral artery. Patients were hospitalized at a stroke
      rehabilitation center, where they underwent a standardized rehabilitation
      program. Clinical, imagiology, laboratory (biomarkers: C-reactive protein, D
      dimer, and fibrinogen, and S100 calcium binding protein beta [S100beta]), and
      functionality assessments were conducted four different times: within 24 hours,
      and at 48 hours, 3 weeks, and 12 weeks after acute stroke. RESULTS: Upper limb
      functioning at 12 weeks was significantly associated with Alberta Stroke Program
      Early CT Score (ASPECTS) score (OR:2.012 [CI:1.349-3.000]; P = 0.001) and
      S100beta protein levels (OR:0.997 [CI:0.994-0.999]; P = 0.007). Advanced age was
      associated with poor upper limb functioning. S100beta protein levels < 140.5 ng/L
      at 48 hours and ASPECTS scores >= 7.5 within 24 hours of admission predicted good
      hand functioning at 12 weeks. Upper limb functioning and general functioning were
      significantly correlated (P < 0.001), with strong negative correlations (all
      correlation coefficients <=-0.586) for all comparisons. CONCLUSION: ASPECTS score
      >= 8 within 24 hours and S100beta protein < 140.5 ng/L at 48 hours predict better
      upper limb functioning, while advanced age predicts worse upper limb functioning
      12 weeks after stroke.

PMID- 30213244
TI  - Neuroprotective ability of TMV coat protein on rat PC-12 cells and it's in silico
      study with LRRK2 receptor.
AB  - OBJECTIVE: Present study was to observe the neuroprotective ability of TMV coat
      protein by observing both in vitro studies on Rat PC-12 cells and in silico
      studies with LRRK2 receptor by molecular docking. METHODS: TMV coat protein was
      extracted out from the stem of Nicotiana tabacum and was purified and identified
      by MALDI-TOF/MS/MS analysis. We confer antioxidant activity of TMV coat protein
      by enzyme activity like superoxide dismutase (SOD), catalase (CAT) and
      glutathione-s-transferase (GST) and nonenzyme content by glutathione (GSH) and
      malondialdehyde (MDA) content. Neuroprotective ability of TMV coat protein was
      observed by determining the enzyme activity and nonenzyme content in treated
      cells that were exposed to neurotoxic shock. In silico studies were done in order
      to observe the molecular docking studies against LRRK2 receptor. RESULTS:
      Antioxidant content was found to be high in TMV coat protein and in treated Rat
      PC-12 cells as well. Enzyme activity and nonenzyme content were determined and
      their levels were found to be in increasing level with respect to the volume of
      0.2 mg/ml of TMV coat protein. In silico studies revealed the binding efficacy of
      TMV coat protein with LRRK2 receptor by observing the molecular docking using
      automated servers. CONCLUSION: From the present study, it was found that TMV coat
      protein can be utilized as neuroprotective agent and inhibitor of LRRK2 receptor.

PMID- 30213245
TI  - Synopsis of Sweet! Mouse Models of Diabetic Kidney Disease.
AB  - Diabetes mellitus (types 1 and 2) is the leading cause of glomerular disease and
      end-stage renal disease in most developed countries, with estimates that one
      third of people living with diabetes will develop diabetic kidney disease (DKD).
      The current standard of care medications slow but do not arrest progression of
      kidney disease, and therefore, therapy for DKD is a highly unmet medical need for
      patients. To discover and test novel and durable new therapies, it is necessary
      to develop animal models of human DKD, which authentically recapitulate the human
      disease state and provide translatable efficacy to human patients. Here, we
      review selected mouse models of human DKD, which demonstrate many of the features
      of type 2 human DKD.

PMID- 30213246
TI  - Cora Du Bois' Brief Stint With the World Health Organization (1950-1951): Right
      Time, Wrong Place.
AB  - Brock Chisholm, director-general of the World Health Organization (WHO) in the
      early 1950s, was heard to say that "one cultural anthropologist [Cora Du Bois]
      was worth one hundred malaria teams." Paul Russell, the leading malariologist at
      the time, responded (privately in his diary) that Chisholm's remark was the sort
      that "one might expect from a psychiatrist planning a world health program."
      George Foster reported that Du Bois "was completely disgusted with" her stay at
      WHO. "They never asked her to do anything. She never followed up." Chisholm was
      not the only one who appreciated her contribution to the work of WHO; other WHO
      programs and offices would have welcomed her contribution. However, by operating
      out of WHO's South-East Asia Regional Office (SEARO), she found herself isolated
      with little chance of her work being reviewed favorably, i.e., the "wrong place."

PMID- 30213247
TI  - Digital Platforms, Gig Economy, Precarious Employment, and the Invisible Hand of
      Social Class.
AB  - Digital platform capitalism, as exemplified by companies like Uber or Lyft has
      the potential to transform employment and working conditions for an increasing
      segment of the worforce. Most digital economy workers are exposed to the health
      damaging precarious employment conditions characteristic of the contemporary
      working class in high income countries. Just as with Guy Standing or Mike
      Savage's "precariat" it might appear that digital platform workers are a new
      social class or that they do not belong to any social class. Yet the class
      conflict interests (wages, benefits, employment and working conditions,
      collective action) of digital platform workers are similar to other members of
      the working class.

PMID- 30213248
TI  - Neoliberalism and Accountability Failure in the Delivery of Services Affecting
      the Health of the Public.
AB  - Since the 1980s, the emergence of neoliberalism as a dominant government paradigm
      has led to increasing instances of accountability failure, resulting in
      significant injuries or death. Employing a grounded theory approach,
      accountability failure is defined and explored through analysis of 18 public
      inquiries and reports in the United Kingdom and Canada. The analysis reveals that
      the combination of a neoliberal policy paradigm and flawed regulation,
      governance, culture, and performance management inevitably led to accountability
      failure. Neoliberal policies have precipitated uncoordinated and underfunded
      regulatory regimes, an oppressive culture focused on financial efficiency at the
      expense of quality, self-serving and willfully blind governance, and underfunded
      and inadequate tools for measuring performance. The evidence suggests that
      organizations have not learned from each other within or between countries,
      revealing a pattern of accountability failure in which citizens are placed at
      risk in their communities and hospitals for preventable injury or death within an
      increasingly politicized government and leadership environment.

PMID- 30213249
TI  - Zolpidem and Facebook Don't Mix.

PMID- 30213250
TI  - Superheroes and Spandex.

PMID- 30213251
TI  - What Are Preprints?

PMID- 30213252
TI  - Peristaltic transport of bi-viscosity fluids through a curved tube: A
      mathematical model for intestinal flow.
AB  - The human intestinal tract is a long, curved tube constituting the final section
      of the digestive system in which nutrients and water are mostly absorbed.
      Motivated by the dynamics of chyme in the intestine, a mathematical model is
      developed to simulate the associated transport phenomena via peristaltic
      transport. Rheology of chyme is modelled using the Nakamura-Sawada bi-viscosity
      non-Newtonian formulation. The intestinal tract is considered as a curved tube
      geometric model. Low Reynolds number (creeping hydrodynamics) and long wavelength
      approximations are taken into consideration. Analytical solutions of the moving
      boundary value problem are derived for velocity field, pressure gradient and
      pressure rise. Streamline flow visualization is achieved with Mathematica
      symbolic software. Peristaltic pumping phenomenon and trapping of the bolus are
      also examined. The influence of curvature parameter, apparent viscosity
      coefficient (rheological parameter) and volumetric flow rate on flow
      characteristics is described. Validation of analytical solutions is achieved with
      a MAPLE17 numerical quadrature algorithm. The work is relevant to improving
      understanding of gastric hydrodynamics and provides a benchmark for further
      computational fluid dynamic simulations.

PMID- 30213253
TI  - Application of on-dose identification and blockchain to prevent drug
      counterfeiting.

PMID- 30213254
TI  - Developmental abnormalities of the brain exposed to childhood maltreatment
      detected by diffusion tensor imaging.
AB  - OBJECTIVE: This study aimed to investigate brain developmental alterations in
      individuals exposed to childhood maltreatment (CM) with dissociative experiences
      and motor coordination symptoms using diffusion tensor imaging on a 3Tesla (3T)
      magnetic resonance (MR) system. METHODS: Five individuals exposed to CM who
      manifest behavioral and developmental problems with dissociative experiences and
      motor coordination symptoms (age range: 14-18 years; all female), as well as
      seven age- and gender-matched normal control individuals, participated in the
      study using a 3T MR system. Diffusion characteristics, as indexed by fractional
      anisotropy (FA), were assessed for cerebral white matter structures. A
      preliminary whole brain analysis was performed complementary to an anatomically
      guided region of interest (ROI) analysis. RESULTS: In individuals exposed to CM,
      scattered decreases in FA were detected in multiple brain regions over the
      frontoparietal and temporal areas in the whole brain map. ROI analysis
      subsequently identified significant decreases in FA (p < 0.05) in the right
      parietal white matter area as well as in the right prefrontal, bilateral
      premotor, bilateral orbitofrontal, and temporal white matter areas in CM-exposed
      individuals compared to that in controls. CONCLUSION: The observed altered
      diffusion characteristics indicate attendant developmental abnormalities within
      the white matter structures, which are associated with the observed clinical and
      behavioral patterns including dissociative experiences and coordination symptoms
      in individuals exposed to CM. The study provides objective evidence regarding the
      effects of CM on brain microstructure.

PMID- 30213255
TI  - Dengue: a growing threat requiring vaccine development for disease prevention.
AB  - Dengue disease is the most prevalent mosquito-borne viral infection in humans. At
      least one half of the global population is estimated at risk of infection and an
      estimated 390 million people are infected each year. Over the past few years,
      dengue burden continued to increase, mainly impacting developing countries.
      Alarming changes in dengue epidemiology were observed highlighting a spread from
      tropical to subtropical regions as well as urban to rural areas. An increase in
      the co-infections with the four serotypes has also been noticed, involving a
      shift in the targeted population from pediatric to adult. Facing these global
      changes, authorities will have to reinforce preventive actions and adapt
      healthcare management. New prophylactic strategies are urgently needed to prevent
      severe forms of dengue disease. The lack of specific antiviral therapies
      available turns vaccine development into a socio-economic challenge. In this
      review, we propose an update on the dengue global trends and different vaccine
      strategies in development. A particular attention will be paid to up-to-date
      information on dengue transmission and the protective efficacy of newly
      commercialized tetravalent dengue vaccine Dengvaxia(r), as well as the most
      advanced candidate vaccines in clinical development.

PMID- 30213256
TI  - Pseudobulbar affect after stroke: a narrative review.
AB  - BACKGROUND: Pseudobulbar affect (PBA) is a neuropsychological condition of
      emotional lability and affective dysregulation associated with a variety of
      neurological conditions such as stroke, traumatic brain disease, and
      neurodegenerative disease. The true prevalence and medico-social burden of PBA
      associated with stroke is unclear. Often confused with post-stroke mood
      disorders, PBA is under-recognized and under-treated. OBJECTIVE: To provide a
      comprehensive narrative synthesis of published literature on the topic of PBA.
      METHODS: Literature review was performed by searching the key words "pseudobulbar
      atrophy", "emotional incontinence," and "stroke" in PubMed. Only manuscripts
      published in English were appraised and relevant content was extracted,
      synthesized, and summarized. RESULTS: A narrative overview was performed on the
      following topics: epidemiology, pathophysiology, clinical features of
      differential diagnosis, impact on public health, and therapeutic options.
      CONCLUSION: PBA remains an under-treated condition with significant psychosocial
      burden on both effected stroke survivors and their families. Advances have been
      made in developing consensus-based clinical diagnostic criteria for PBA. Early
      identification and prompt initiation of therapeutic measures are required in
      these stroke patients. Further research is needed to develop better PBA
      diagnostic criteria and more cost-effective therapeutic treatment options.

PMID- 30213257
TI  - The Curious Neglect of High Functioning After Psychopathology: The Case of
      Depression.
AB  - We address a key issue at the intersection of emotion, psychopathology, and
      public health-the startling lack of attention to people who experience benign
      outcomes, and even flourish, after recovering from depression. A rereading of the
      epidemiological literature suggests that the orthodox view of depression as
      chronic, recurrent, and lifelong is overstated. A significant subset of people
      recover and thrive after depression, yet research on such individuals has been
      rare. To facilitate work on this topic, we present a generative research
      framework. This framework includes (a) a proposed definition of healthy end-state
      functioning that goes beyond a reduction in clinical symptoms, (b)
      recommendations for specific measures to assess high functioning, and (c) a road
      map for a research agenda aimed at discovering how and why people flourish after
      emotional disturbance. Given that depression remains the most burdensome health
      condition worldwide, focus on what makes these excellent outcomes possible has
      enormous significance for the public health.

PMID- 30213259
TI  - Correction to: Comparative genomics of the wheat fungal pathogen Pyrenophora
      tritici-repentis reveals chromosomal variations and genome plasticity.
AB  - ?.

PMID- 30213260
TI  - Evaluation on prognostic efficacy of lymph nodes ratio (LNR) and log odds of
      positive lymph nodes (LODDS) in complicated colon cancer: the first study in
      emergency surgery.
AB  - BACKGROUND: Lymph node involvement is one of the most important prognostic
      factors in colon cancer. Twelve is considered the minimum number of lymph nodes
      necessary to retain reliable tumour staging, but several factors can potentially
      influence the lymph node harvesting. Emergent surgery for complicated colon
      cancer (perforation, occlusion, bleeding) could represent an obstacle to reach
      the benchmark of 12 nodes with an accurate lymphadenectomy. So, an efficient
      classification system of lymphatic involvement is crucial to define the
      prognosis, the indication to adjuvant therapy and the follow-up. This is the
      first study with the aim to evaluate the efficacy of lymph nodes ratio (LNR) and
      log odds of positive lymph nodes (LODDS) in the prognostic assessment of patients
      who undergo to urgent surgery for complicated colonic cancer. METHODS: This is a
      retrospective study carried out on patients who underwent urgent colonic
      resection for complicated cancer (occlusion, perforation, bleeding, sepsis). We
      collected clinical, pathological and follow-up data of 320 patients. Two hundred
      two patients met the inclusion criteria and were distributed into three groups
      according to parameter N of TNM, LNR and LODDS. Survival analysis was performed
      by Kaplan-Meier curves, investigating both overall survival (OS) and disease-free
      survival (DFS). RESULTS: The median number of harvested lymph nodes was 17. In
      78.71% (n = 159) of cases, at least 12 lymph nodes were examined. Regarding OS,
      significant differences from survival curves emerged for ASA score, surgical
      indication, tumour grading, T parameter, tumour stage, N parameter, LNR and
      LODDS. In multivariate analysis, only LODDS was found to be an independent
      prognostic factor. Concerning DFS, we found significant differences between
      survival curves of sex, surgical indication, T parameter, tumour stage, N
      parameter, LNR and LODDS, but none of these confirmed its prognostic power in
      multivariate analysis. CONCLUSIONS: We found that N, LNR and LODDS are all
      related to 5-year OS and DFS with statistical significance, but only LODDS was
      found to be an independent prognostic factor for OS in multivariate analysis.

PMID- 30213258
TI  - Reliability, validity, and responsiveness of three scales for measuring balance
      in patients with chronic stroke.
AB  - BACKGROUND: Various outcome measures are used for the assessment of balance and
      mobility in patients with stroke. The purpose of the present study was to examine
      test-retest reliability, construct validity, and responsiveness of the Timed Up
      and Go Test (TUG), Berg Balance Scale (BBS), and Dynamic Gait Index (DGI) for
      measuring balance in patients with chronic stroke. METHODS: Fifty-six patients
      (39 male and 17 female) with chronic stroke participated in this study. A senior
      physical therapist assessed the test-retest reliability and validity of three
      scales, including the DGI, TUG, and BBS over two testing sessions. In addition,
      the third assessment of each scale was taken at the time of discharge to
      determine the responsiveness of the three outcome measures. RESULTS: The
      reliability of the TUG (intraclass correlation coefficient [ICC2,1] = 0.98), DGI
      (ICC2,1 = 0.98) and BBS (ICC2,1 = 0.99) were excellent. The standard error of
      measurement (SEM) of the TUG, DGI, and BBS were 1.16, 0.71, and 0.98,
      respectively. The minimal detectable change (MDC) of the TUG, DGI, and BBS were
      3.2, 1.9, and 2.7, respectively. There was a significant correlation found
      between the DGI and BBS (first reading [r] = 0.75; second reading [r] = 0.77),
      TUG and BBS (first reading [r] = -.52; second reading [r] = -.53), and the TUG
      and DGI (first reading [r] = 0.45; second reading [r] = 0.48), respectively.
      CONCLUSIONS: The test-retest reliability of the TUG, BBS, and DGI was excellent.
      The DGI demonstrated slightly better responsiveness than TUG and BBS. However,
      the small sample size of this study limits the validity of the results.

PMID- 30213261
TI  - Evaluation of blood flow on the remnant distal bowel during left-sided colectomy.
AB  - Adequate blood flow in anastomosis is of paramount importance to prevent
      anastomotic leakage. However, it is sometimes difficult to predict the viability
      of the intestine during surgery. During left-sided colectomy, blood flow on the
      remnant distal bowel is supplied only from the middle and inferior rectal
      arteries. The blood backflow after the root ligation of the inferior mesenteric
      artery is often said to be kept up to promontorium levels; however, this premise
      is actually based on experience, without reliable evidence. Here, we introduce
      the intraoperative evaluation of blood flow on the remnant distal bowel during
      left-sided colectomy using an indocyanine green fluorescence technique.

PMID- 30213263
TI  - Assessing the credibility and transferability of the patient compassion model in
      non-cancer palliative populations.
AB  - BACKGROUND: A lack of evidence and psychometrically sound measures of compassion
      necessitated the development of the first known, empirically derived, theoretical
      Patient Compassion Model (PCM) generated from qualitative interviews with
      advanced cancer inpatients. We aimed to assess the credibility and
      transferability of the PCM across diverse palliative populations and settings.
      METHODS: Semi-structured, audio-recorded qualitative interviews were conducted
      with 20 patients with life-limiting diagnoses, recruited from 4 settings (acute
      care, homecare, residential care, and hospice). Participants were first asked to
      share their understandings and experiences of compassion. They were then
      presented with an overview of the PCM and asked to determine whether: 1) the
      model resonated with their understanding and experiences of compassion; 2) the
      model required any modification(s); 3) they had further insights on the model's
      domains and/or themes. Members of the research team analyzed the qualitative data
      using constant comparative analysis. RESULTS: Both patients' personal
      perspectives of compassion prior to viewing the model and their specific feedback
      after being provided an overview of the model confirmed the credibility and
      transferability of the PCM. While new codes were incorporated into the original
      coding schema, no new domains or themes emerged from this study sample. These
      additional codes provided a more comprehensive understanding of the nuances
      within the domains and themes of the PCM that will aid in the generation of items
      for an ongoing study to develop a patient reported measure of compassion.
      CONCLUSIONS: A diverse palliative patient population confirmed the credibility
      and transferability of the PCM within palliative care, extending the rigour and
      applicability of the PCM that was originally developed within an advanced cancer
      population. The views of a diverse palliative patient population on compassion
      helped to validate previous codes and supplement the existing coding schema,
      informing the development of a guiding framework for the generation of a patient
      reported measure of compassion.

PMID- 30213262
TI  - Longitudinal associations of in utero and early life near-roadway air pollution
      with trajectories of childhood body mass index.
AB  - BACKGROUND: Evidence suggests that childhood near-roadway air pollution (NRAP)
      exposures contribute to increased body mass index (BMI); however, effects of NRAP
      exposure during the vulnerable periods including in utero and first year of life
      have yet to be established. In this study, we examined whether exposure to
      elevated concentrations of NRAP during in utero and/or first year of life
      increase childhood BMI growth. METHODS: Participants in the Children's Health
      Study enrolled from 2002 to 2003 with annual visits over a four-year period and
      who changed residences before study entry were included (n = 2318). Annual height
      and weight were measured and lifetime residential NRAP exposures including in
      utero and first year of life periods were estimated by nitrogen oxides (NOx)
      using the California line-source dispersion model. Linear mixed effects models
      assessed in utero or first year near-road freeway and non-freeway NOx exposures
      and BMI growth after adjusting for age, sex, race/ethnicity, parental education,
      Spanish questionnaire, and later childhood near-road NOx exposure. RESULTS: A two
      standard deviation difference in first year of life near-road freeway NOx
      exposure was associated with a 0.1 kg/m2 (95% confidence interval (CI): 0.03,
      0.2) faster increase in BMI growth per year and a 0.5 kg/m2 (95% CI: 0.02, 0.9)
      higher attained BMI at age 10 years. CONCLUSIONS: Higher exposure to early life
      NRAP increased the rate of change of childhood BMI and resulted in a higher
      attained BMI at age 10 years that were independent of later childhood exposures.
      These findings suggest that elevated early life NRAP exposures contribute to
      increased obesity risk in children.

PMID- 30213264
TI  - Intraosseous intraneural perineurioma derived from the inferior alveolar nerve
      with an abnormality of chromosome 22 and expression of the BCR-ABL fusion gene:
      report of a case and review of recent literature.
AB  - BACKGROUND: Perineurioma (PN) is a peripheral nerve disease that primarily
      develops in the limbs and trunk and very rarely occurs in the oral cavity. PN is
      classified into two types: intraneural perineurioma (INPN) and soft tissue
      perineurioma (extraneural perineurioma, ENPN). In this article, we report a
      patient with mandibular body INPN derived from the perineurium of the inferior
      alveolar nerve. CASE PRESENTATION: The patient was a 43-year-old male. He
      consulted our department for a detailed examination of the right mandibular body.
      A biopsy was performed at another hospital and he was diagnosed with a
      schwannoma. At his first visit, hypesthesia extending from the right lower lip to
      the mental region was recognized and enlargement of the right mandibular canal
      was confirmed with X-ray CT and MRI. Considering the possibility of future tumor
      growth, we extirpated the tumor under general anesthesia. Cystic tumor was seen
      continuously in the inferior alveolar nerve. Immunohistologically, the tumor
      cells were positive for Glut-1, weakly positive for EMA, and weakly positive for
      Claudin-1, and the histopathological diagnosis was INPN. In addition, absence of
      the BCR region of chromosome 22 and expression of the BCR-ABL fusion gene were
      observed by fluorescent in situ hybridization (FISH), and a chromosome 22
      abnormality was confirmed. These findings indicated that the disease was a
      neoplastic lesion. CONCLUSION: Expression of the BCR-ABL fusion gene in INPN that
      develops in the oral cavity is thought to be very rare, and to the best of our
      knowledge, ours is the first case to be reported in the literature. About three
      postoperative years have passed, but findings suggestive of recurrence have not
      been observed.

PMID- 30213265
TI  - Correction to: Jejunal pouch reconstruction after total gastrectomy is associated
      with better short-term absorption capacity and quality of life in early-stage
      gastric cancer patients.
AB  - Following publication of the original article [1], the authors reported that one
      of the authors' names is spelled incorrectly.

PMID- 30213266
TI  - Progress of preoperative and postoperative radiotherapy in gastric cancer.
AB  - BACKGROUND: Gastric carcinoma, a highly common malignant tumor, is treated mainly
      by surgery. Meanwhile, radiotherapy is attracting increased attention as a
      crucial locoregional therapy. However, the application of radiotherapy in gastric
      carcinoma is still limited and radiation standards remain debatable. MAIN BODY:
      The use of preoperative radiotherapy for treating gastroesophageal junction
      cancer has advanced. However, additional phase III clinical trials are needed to
      further verify the therapeutic value of preoperative radiotherapy for gastric
      cancer. Patients with D1 or D1 plus lymphadenectomy can benefit from
      postoperative radiotherapy obviously, and postoperative radiotherapy may be
      effective for patients with D2 lymphadenectomy with a high N stage. The target
      volume delineation of preoperative and postoperative radiotherapy should be based
      on clinical experience and the characteristics of lymphatic drainage.
      CONCLUSIONS: With the advancement of radiotherapy technology, preoperative and
      postoperative radiotherapy are becoming increasingly accepted as important
      auxiliary treatments for gastric cancer.

PMID- 30213268
TI  - Correction to: Palliative long-term abdominal drains versus repeated drainage in
      individuals with untreatable ascites due to advanced cirrhosis: study protocol
      for a feasibility randomised controlled trial.
AB  - Following publication of the original article [1], the authors reported that the
      figure legend for Figure 3 was absent. In addition, they have requested
      additional funding information to be added. In this Correction the initial and
      updated funding information are shown. The original publication of this article
      has been corrected.

PMID- 30213269
TI  - Revealing cellular and molecular complexity of the central nervous system using
      single cell sequencing.
AB  - The mammalian central nervous system (CNS) is one of the most complex systems,
      with thousands of cell types and subtypes with distinct and unique morphology and
      gene expression profiles. Based on classic histological methods and conventional
      cellular and molecular approaches, single cell sequencing is becoming a powerful
      tool to uncover the complexity of the CNS. In this review, we summarize the
      principle of single cell sequencing and highlight its use for studying the
      development of neural stem cells, neural progenitors, and distinct neurons. By
      revealing transcriptomes in each individual cell using single cell sequencing, we
      are now able to dissect the cellular heterogeneity of a hundred billion cells in
      the CNS and comprehensively investigate mechanisms of brain development and
      function at the cellular and molecular levels.

PMID- 30213270
TI  - Novel variant of reversed midgut rotation - retro-arterial proximal jejunum and
      transverse colon: a case report and review of the literature.
AB  - BACKGROUND: Reversed rotation of the midgut is the rarest variation of midgut
      malrotations, which are congenital disorders that result from aberrant rotation
      and fixation of the midgut during embryological development. Common complications
      of these disorders are small bowel obstruction by volvulus or peritoneal bands,
      usually occurring in early infancy. CASE PRESENTATION: A 23-year-old Caucasian
      woman presented with recurrent abdominal pain. A contrast-enhanced multidetector
      computed tomography study revealed a novel variant of reversed rotation of the
      midgut. Besides the specific finding of a retro-arterial transverse colon, we
      also found the proximal jejunum to cross posterior to the mesenteric root, a
      variation that has not been reported in the literature so far. In this case,
      substantial symptomatic relief was achieved with conservative management.
      CONCLUSIONS: The hypothesis of a double reversed rotation of the pre-arterial
      segment of the umbilical loop around the superior mesenteric artery axis provides
      a possible explanation for this anomaly. There is no evidence-based consensus on
      the management of patients presenting with non-symptomatic or mildly symptomatic
      intestinal malrotations. In this case, radiologic and clinical presentations
      excluded acute small bowel obstruction, and surgical intervention was avoided.

PMID- 30213271
TI  - Escherichia coli recombinant sperm immobilizing factor RecX as a potential
      vaginal contraceptive.
AB  - BACKGROUND: To control the overpopulation and unintended pregnancies, vaginal
      contraceptives have gained recent surge of interest because of its topical
      application with possible avoidance of systemic effects. However non-specific
      cytotoxicity associated with detergent-based synthetic vaginal contraceptive
      agents limits their use and generates considerable interest in the development of
      vaginal contraceptives of biological origin for controlling reproduction and
      ultimately growing population. In this study, we have cloned, over-expressed an
      Escherichia coli gene encoding a sperm immobilizing factor (SIF) that inhibits
      sperm motility for the development of vaginal contraceptive from a biological
      source i.e. E. coli. The contraceptive efficacy of the Escherichia coli
      recombinant sperm immobilizing factor (r-SIF) was also determined. METHODS:
      Genomic DNA library of an E. coli strain isolated from semen sample of an
      infertile male was constructed for the identification and cloning of E. coli SIF
      coding gene. This gene was sub-cloned in pBADmycHisB for over-expression and the
      r-SIF was purified using Ni-NTA affinity chromatography. Effect of r-SIF on mouse
      sperm motility, viability and on morphology was evaluated. Binding of r-SIF to
      mouse sperm was demonstrated by fluorescent labeling. Contraceptive efficacy of r
      SIF was checked in murine model. RESULTS: Genomic library resulted in five
      hundred transformants; five clones were found positive for sperm immobilizing
      activity. The protein product of the insert DNA sequence in one of the
      transformants showed maximum sperm immobilizing activity. Sequence analysis of
      ORFs in the insert revealed homology to recX on both nucleotide and protein
      level. 40 MUg of the purified r-SIF showed immediate spermicidal activity in
      vitro for mouse sperm. Scanning electron micrograph of the r-SIF treated sperm
      showed intense morphological damage to sperm. FITC labeled r-SIF showed highest
      fluorescence at the head region of the sperm. 5 MUg of purified r-SIF exhibited a
      complete contraceptive effect in mouse model. CONCLUSION: r-SIF could be seen as
      potential target to be developed as potent and safe vaginal contraceptive in
      future.

PMID- 30213267
TI  - Sympathetic tales: subdivisons of the autonomic nervous system and the impact of
      developmental studies.
AB  - Remarkable progress in a range of biomedical disciplines has promoted the
      understanding of the cellular components of the autonomic nervous system and
      their differentiation during development to a critical level. Characterization of
      the gene expression fingerprints of individual neurons and identification of the
      key regulators of autonomic neuron differentiation enables us to comprehend the
      development of different sets of autonomic neurons. Their individual functional
      properties emerge as a consequence of differential gene expression initiated by
      the action of specific developmental regulators. In this review, we delineate the
      anatomical and physiological observations that led to the subdivision into
      sympathetic and parasympathetic domains and analyze how the recent molecular
      insights melt into and challenge the classical description of the autonomic
      nervous system.

PMID- 30213272
TI  - Control of directionality of chromatin folding for the inter- and intra-domain
      contacts at the Tfap2c-Bmp7 locus.
AB  - BACKGROUND: Contact domains of chromatin serve as a fundamental unit to regulate
      action of enhancers for target genes. Looping between a pair of CCCTC-binding
      factor (CTCF)-binding sites in convergent orientations underlies the formation of
      contact domains, while those in divergent orientations establish domain
      boundaries. However, every CTCF site is not necessarily engaged in loop or
      boundary structures, leaving functions of CTCF in varied genomic contexts still
      elusive. The locus containing Tfap2c and Bmp7 encompasses two contact domains
      separated by a region between the two genes, termed transition zone (TZ),
      characterized by two arrays of CTCF sites in divergent configuration. In this
      study, we created deletion and inversion alleles of these and other regions
      across the locus and investigated how they impinge on the conformation. RESULTS:
      Deletion of the whole two CTCF arrays with the CRISPR/Cas9 system resulted in
      impairment of blocking of chromatin contacts by the TZ, as assessed by the
      circular chromatin conformation capture assay (4C-seq). Deletion and inversion of
      either of the two arrays similarly, but less pronouncedly, led to reduction in
      the blocking activity. Thus, the divergent configuration provides the TZ with the
      strong boundary activity. Uniquely, we show the TZ harbors a 50-kb region within
      one of the two arrays that contacts broadly with the both flanking intervals,
      regardless of the presence or orientation of the other CTCF array. Further, we
      show the boundary CTCF array has little impact on intra-domain folding; instead,
      locally associating CTCF sites greatly affect it. CONCLUSIONS: Our results show
      that the TZ not only separates the two domains, but also bears a wide interval
      that shows isotropic behavior of chromatin folding, indicating a potentially
      complex nature of actual boundaries in the genome. We also show that CTCF-binding
      sites inside a domain greatly contribute to the intra-domain folding of
      chromatin. Thus, the study reveals diverse and context-dependent roles of CTCF in
      organizing chromatin conformation at different levels.

PMID- 30213273
TI  - Skeletal muscle-derived cell implantation for the treatment of sphincter-related
      faecal incontinence.
AB  - BACKGROUND: In an earlier pilot study with 10 women, we investigated a new
      approach for therapy of faecal incontinence (FI) due to obstetric trauma,
      involving ultrasound-guided injection of autologous skeletal muscle-derived cells
      (SMDC) into the external anal sphincter (EAS), and observed significant
      improvement. In the current study, we tested this therapeutic approach in an
      extended patient group: male and female patients suffering from FI due to EAS
      damage and/or atrophy. Furthermore, feasibility of lower cell counts and cryo
      preserved SMDC was assessed. METHODS: In this single-centre, explorative,
      baseline-controlled clinical trial, each patient (n = 39; mean age 60.6 +/- 13.81
      years) received 79.4 +/- 22.5 * 106 cryo-preserved autologous SMDC. Changes in FI
      parameters, Fecal Incontinence Quality of Life (FIQL), anorectal manometry and
      safety from baseline to 1, 6 and 12 months post implantation were evaluated.
      RESULTS: SMDC used in this trial contained a high percentage of myogenic
      expressing (CD56+) and muscle stem cell marker-expressing (Pax7+, Myf5+) cells.
      Intervention was well tolerated without any serious adverse events. After 12
      months, the number of weekly incontinence episodes (WIE, primary variable), FIQL
      and patient condition had improved significantly. In 80.6% of males and 78.4% of
      females, the WIE frequency decreased by at least 50%; Wexner scores and severity
      of FI complaints decreased significantly, independent of gender and cause of FI.
      CONCLUSIONS: Injection of SMDCs into the EAS effectively improved sphincter
      related FI due to EAS damage and/or atrophy in males and females. When confirmed
      in a larger, placebo-controlled trial, this minimal invasive procedure has the
      potential to become first-line therapy for FI. TRIAL REGISTRATION: EU Clinical
      Trials Register, EudraCT 2010-023826-19 (Date of registration: 08.11.2010).

PMID- 30213274
TI  - FANCC localizes with UNC5A at neurite outgrowth and promotes neuritogenesis.
AB  - OBJECTIVE: The Uncoordinated 5A (UNC5A) protein is part of a family of receptors
      that play roles in axonal pathfinding and cell migration. We previously showed
      that the Fanconi anemia C protein (FANCC) interacts with UNC5A and delays UNC5A
      mediated apoptosis. FANCC is a predominantly cytoplasmic protein that has
      multiple functions including DNA damage signaling, oxygen radical metabolism,
      signal transduction, transcriptional regulation and apoptosis. Given the direct
      interaction between FANCC and UNC5A and that FANCC interferes with UNC5A-mediated
      apoptosis, we explored the possibility that FANCC might play a role in axonal
      like growth processes. RESULTS: Here we show that FANCC and UNC5A are localized
      to regions of neurite outgrowth during neuronal cell differentiation. We also
      show that absence of FANCC is required for neurite outgrowth. In addition, FANCC
      seems required for UNC5A expression. Results from this study combined with our
      previous report suggest that FANCC plays a role in tissue development through the
      regulation of UNC5A-mediated functions.

PMID- 30213275
TI  - Do hotspots fuel malaria transmission: a village-scale spatio-temporal analysis
      of a 2-year cohort study in The Gambia.
AB  - BACKGROUND: Despite the biological plausibility of hotspots fueling malaria
      transmission, the evidence to support this concept has been mixed. If
      transmission spreads from high burden to low burden households in a consistent
      manner, then this could have important implications for control and elimination
      program development. METHODS: Data from a longitudinal cohort in The Gambia was
      analyzed. All consenting individuals residing in 12 villages across the country
      were sampled monthly from June (dry season) to December 2013 (wet season), in
      April 2014 (mid dry season), and monthly from June to December 2014. A study
      nurse stationed within each village recorded passively detected malaria episodes
      between visits. Plasmodium falciparum infections were determined by polymerase
      chain reaction and analyzed using a geostatistical model. RESULTS: Household
      level observed monthly incidence ranged from 0 to 0.50 infection per person
      (interquartile range = 0.02-0.10) across the sampling months, and high burden
      households exist across all study villages. There was limited evidence of a
      spatio-temporal pattern at the monthly timescale irrespective of transmission
      intensity. Within-household transmission was the most plausible hypothesis
      examined to explain the observed heterogeneity in infections. CONCLUSIONS: Within
      village malaria transmission patterns are concentrated in a small proportion of
      high burden households, but patterns are stochastic regardless of endemicity. Our
      findings support the notion of transmission occurring at the household and
      village scales but not the use of a targeted approach to interrupt spreading of
      infections from high to low burden areas within villages in this setting.

PMID- 30213277
TI  - Correction to: Histone demethylase KDM4D promotes gastrointestinal stromal tumor
      progression through HIF1beta/VEGFA signalling.
AB  - After the publication of this work [1] an error was noticed in Fig. 7e, in which
      the incorrect information is shown. The updated figure included in this
      correction now shows the quantification of tumor microvessel density. This
      correction does not affect the findings or conclusions of the article.
      Nevertheless, we apologize for the inconvenience.

PMID- 30213276
TI  - A journey through chaos and calmness: experiences of mindfulness training in
      patients with depressive symptoms after a recent coronary event - a qualitative
      diary content analysis.
AB  - BACKGROUND: Psychological distress with symptoms of depression and anxiety is
      common and unrecognized in patients with coronary artery disease (CAD). Efforts
      have been made to treat psychological distress in CAD with both conventional
      methods, such as antidepressant drugs and psychotherapy, and non-conventional
      methods, such as stress management courses. However, studies focusing on the
      experiences of mindfulness training in this population are still scarce.
      Therefore, the aim of this study was to explore immediate experiences of
      mindfulness practice among CAD patients with depressive symptoms. METHODS: A
      qualitative content analysis of diary entries, written immediately after practice
      sessions and continuously during an 8-week long Mindfulness Based Stress
      Reduction course (MBSR), was applied. RESULTS: Twelve respondents participated in
      the study. The main category: a journey through chaos and calmness captured the
      participants' concurrent experiences of challenges and rewards over time. This
      journey appears to reflect a progressive development culminating in the
      harvesting of the fruits of practice at the end of the mindfulness training.
      Descriptions of various challenging facets of mindfulness practice - both
      physical and psychological - commonly occurred during the whole course, although
      distressing experiences were more predominant during the first half. Furthermore,
      the diary entries showed a wide variety of ways of dealing with these struggles,
      including both constructive and less constructive strategies of facing difficult
      experiences. As the weeks passed, participants more frequently described an
      enhanced ability to concentrate, relax and deal with distractions. They also
      developed their capacity to observe the content of their mind and described how
      the practice began to yield rewards in the form of well-being and a sense of
      mastery. CONCLUSIONS: Introducing MBSR in the aftermath of a cardiac event, when
      depressive symptoms are present, is a complex and delicate challenge in clinical
      practice. More nuanced information about what to expect as well as the addition
      of motivational support and skillful guidance during the course should be given
      in accordance with the participants' experiences and needs. TRIAL REGISTRATION:
      The trial was retrospectively registered in clinicaltrials.gov (registration
      number: NCT03340948 ).

PMID- 30213278
TI  - Prediction of psychosis in prodrome: development and validation of a simple,
      personalized risk calculator.
AB  - BACKGROUND: This study aim to derive and validate a simple and well-performing
      risk calculator (RC) for predicting psychosis in individual patients at clinical
      high risk (CHR). METHODS: From the ongoing ShangHai-At-Risk-for-Psychosis (SHARP)
      program, 417 CHR cases were identified based on the Structured Interview for
      Prodromal Symptoms (SIPS), of whom 349 had at least 1-year follow-up assessment.
      Of these 349 cases, 83 converted to psychosis. Logistic regression was used to
      build a multivariate model to predict conversion. The area under the receiver
      operating characteristic (ROC) curve (AUC) was used to test the effectiveness of
      the SIPS-RC. Second, an independent sample of 100 CHR subjects was recruited
      based on an identical baseline and follow-up procedures to validate the
      performance of the SIPS-RC. RESULTS: Four predictors (each based on a subset of
      SIPS-based items) were used to construct the SIPS-RC: (1) functional decline; (2)
      positive symptoms (unusual thoughts, suspiciousness); (3) negative symptoms
      (social anhedonia, expression of emotion, ideational richness); and (4) general
      symptoms (dysphoric mood). The SIPS-RC showed moderate discrimination of
      subsequent transition to psychosis with an AUC of 0.744 (p < 0.001). A risk
      estimate of 25% or higher had around 75% accuracy for predicting psychosis. The
      personalized risk generated by the SIPS-RC provided a solid estimate of
      conversion outcomes in the independent validation sample, with an AUC of 0.804
      [95% confidence interval (CI) 0.662-0.951]. CONCLUSION: The SIPS-RC, which is
      simple and easy to use, can perform in the same manner as the NAPLS-2 RC in the
      Chinese clinical population. Such a tool may be used by clinicians to counsel
      appropriately their patients about clinical monitor v. potential treatment
      options.

PMID- 30213279
TI  - Nutrition and cancer: prevention and survival.
AB  - Cancer is increasing worldwide. Patterns of cancer are also changing. The
      evidence is summarised in the 2018 World Cancer Research Fund/American Institute
      for Cancer Research report Diet, Nutrition, Physical Activity and Cancer: a
      Global Perspective. The plasticity of cancer patterns implicates environmental
      factors as determinants of cancer, and nutrition influences key cellular and
      molecular processes that characterise cancer. Epidemiology identifies
      associations between aspects of diet, nutrition, and physical activity with one
      or more cancers; there is evidence for plausible mechanisms that imply that these
      are causal. Some nutritional exposures (alcohol and processed meat) are likely
      causal factors, but no singular factor protects against cancer (except dietary
      fibre for colorectal cancer). Cancer protection mainly derives from a systemic
      metabolic environment that promotes healthy cell replication and tissue
      integrity. Such a nutritional state reflects avoiding excess adiposity through
      healthy dietary patterns rich in plant foods (legumes, wholegrains, pulses,
      vegetables and fruits), with modest meat, fish and dairy, low in alcohol and salt
      preserved foods, and an active way of life, avoiding sedentary behaviours. Less
      is known about the impact of nutritional interventions in people with a diagnosis
      of cancer, but nutrition including adiposity and physical activity predict breast
      cancer outcome. Promoting healthy ways of life requires public information and
      education, but alone these do not generate change; a socio-political and cultural
      environment that is conducive to adopting healthy behaviours is needed.
      Uncertainties in the evidence offer promising directions for future research, but
      sufficient is known to act as a basis for public policy and clinical practice.

PMID- 30213280
TI  - Resolution of Carotid Artery Dissection Confirmed by DANTE-SPACE MRI Sequence.

PMID- 30213281
TI  - The effect of 6-week zinc supplement and weight training on the blood lipids of
      the sedentaries and athletes.
AB  - In this study, we aimed to investigate the effect of 6 weeks of zinc
      supplementation and weight training on blood lipids of sedentary and athletes.
      Research group consists of total 40 males; 20 athletes who do regularly physical
      exercises and 20 sedentary volunteers. The volunteers were divided into four
      groups. These groups were constituted in that way: the first group is a natural
      sedentary group which called control group as well (S); the second group is
      another sedentary group which is supplied with only zinc (Z+S); the third group
      is training group which composing of athletes and is supplied with zinc (Z+T);
      the fourth group is the natural training group or athletes (T). From the
      beginning of the study to the end of 6-weeks of training, the participants gave
      blood samples before and after every application order to measure the total
      cholesterol, LDL cholesterol and HDL cholesterol and the levels of Triglyceride.
      This study identifies that the values of the total cholesterol, LDL cholesterol
      and Triglyceride of the groups which were supplied with zinc supplement
      decreased, whereas the levels of HDL cholesterol increased in these groups.
      Consequently, this work demonstrates that the 6-weeks zinc supplement and
      training can make a significant contribution to the performance by changing
      positively the levels of blood lipid.

PMID- 30213282
TI  - Insecticidal effects of the Olea europaea subsp. laperrinei extracts on the flour
      Pyralid Ephestia kuehniella.
AB  - In the present study, the aerial parts of the Laperrine olive (Olea europaea
      subsp. Laperrinei) are subjected to acid extraction and the chemical composition
      of the extracts is determined by HPLC-DAD. The main compounds found in all of
      extracts are: hydroxytyrosol (30.45%), tyrosol (0.69%), oleuropein (32.76%),
      ferrulic acid (17.77%), quercetin (31.57%) and hesperetin (6.90%).The extracts
      obtained from the leafy stems of Laperrine olive tree are tested on the moth
      Ephestia kuehniella flour. Their administration by inhalation of newly exuviated
      chrysalises extends the duration of nymphalid development and disturbs the
      exuviated adults reproduction, by reducing the period in which the eggs are being
      laid. Thus, compared to the control insects, the number of eggs laid by treated
      females is significantly reduced after the treatment by extracts. Besides, the
      administration of different extracts of adult butterflies has a premature
      mortality effect.

PMID- 30213283
TI  - Determination of inhibitory activities of enzymes, related to Alzheimer's disease
      and diabetes mellitus of plane tree (Platanus orientalis L.) extracts and their
      antioxidant, antimicrobial and anticancer activities.
AB  - Plane tree (Platanus orientalis L.) leaves have been employed for centuries in
      various countries due to their pharmacological value. Therefore, determination of
      the biological activity of the leaves is of interest. The aim of the study was to
      evaluate the inhibitory effects against Alzheimer's disease-related enzymes
      Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE), diabetes mellitus
      related enzymes alpha-glucosidase and alpha-amylase. The antioxidant, anticancer,
      and antimicrobial activities of the leaves were also studied. According to the
      results, both water and methanol extracts of P. orientalis demonstrated more
      alpha-glucosidase and alpha-amylase inhibition activity than the antidiabetic
      drug-acarbose at the same concentration level. In addition, extracts showed good
      inhibition activity against AChE and BuChE. Significant results were obtained
      regarding antioxidant, anticancer, and antimicrobial activities. These results
      are very promising especially for the improvement of pharmaceutical formulations
      to treat various diseases such as age-related diseases, cancer, diabetes etc. and
      it is necessary to conduct further experiments.

PMID- 30213284
TI  - Genetic variation of yellow pistachio hard scale, Lepidosaphes pistaciae
      Archangelskaya (Hem.: Diaspididae) populations in Kerman province, Iran revealed
      by ISSR markers.
AB  - Yellow pistachio hard scale, Lepidosaphes pistaciae (Hem.: Coccoidea:
      Diaspididae) is one of the detrimental pests to pistachio trees. This pest is
      distributed throughout the pistachio producing regions of Iran. It is complex
      species, having distinct genetic variation. As genetically diversity awareness is
      essential for identification and management, the diaspidid samples selected from
      10 infected region and used to test hypotheses about the genetic variability
      between and within its populations, during 2016. Inter simple sequence repeat
      (ISSR) molecular marker was used to assess genetic diversity. Extracted DNA of
      specimens amplified with nine ISSR primers, six of primers showed the best
      polymorphism. After observation and scoring bands patterns, data were analyzed
      with NTSYS ver. 2.02 and POPGENE ver. 1.31 software. Results showed that the
      bands are in the range between 100 and 2000 bp. The used ISSR primers generated
      63 polymorphic fragments, and the average heterozygosity for each primer was
      0.266 and the maximum number of bands were recorded for primer SMR7. A dendrogram
      based on the Unweighted Pair Group Method with Arithmetic mean (UPGMA) method
      placed them in three groups also, Anar and Baft populations were the most
      difference among populations. The dendrogram includes the group A (comprise
      populations collected from Baft, Bardsir, Zarand, Sirjan and Shahrbabak), group B
      (including populations collected from north Kerman, south Kerman, Kabootarkhan,
      and Rafsanjan) and group C (including populations collected from Anar). The
      results showed that ISSR markers technique is able to detect the genetic
      diversity among the yellow pistachio hard scale populations of various commercial
      pistachio cultivars within the pistachio orchards, in Kerman, Iran.

PMID- 30213285
TI  - Lentiviral-mediated BCL2 gene knockdown using comparative microRNA adaptive
      shRNAs.
AB  - B-cell lymphoma 2 (BCL2) family proteins play a critical role in tuning cell
      death processes. Almost in half of all human cancers, a dysregulation in BCL2
      family gene expression has been shown which made it an impressive target for
      human gene therapy as a novel approach in cancers. In this study we will optimize
      lentiviral-mediated RNA interference (RNAi), recombinant lentiviruses
      accommodating anti-BCL2 micro adaptive short hairpin RNAs (shRNAs), to
      downregulate BCL2 in human embryonic kidney 293T (HEK293T) cells to produce
      stable cell lines. We tested 4 different DharmaconTM GIPZTM shRNAmir lentiviral
      vectors targeting BCL2 in different positions and a pGIPZ non-silencing shRNAmir
      lentiviral vector (as a negative control). Lentivirus packaging was performed by
      the calcium phosphate precipitation method. HEK293T cells were transduced by each
      type of recombinant lentiviruses individually and selected by puromycin within 10
      days. The relative mRNA level and protein expression were assayed by using real
      time polymerase chain reaction (PCR) technic and western blotting, respectively.
      Lentivirus (LV) packaging was performed in high efficiency (transfection rate was
      > 90%). Recombinant viruses of 4 expression vector addition to a control vector
      were produced then transduced to HEK293T cells successfully. All the 4 cell
      groups showed a significant down regulation of BCL2 gene (~90-95%) at mRNA level
      compared to the control group (p<0.01) but differences between silenced groups
      were not significant (P > 0.05). We showed that the lentivirus-mediated RNAi
      technique is an efficient method to establish HEK293 cell lines with stable down
      regulation of BCL2 gene.

PMID- 30213286
TI  - MiR-33b inhibits osteosarcoma cell proliferation through suppression of
      glycolysis by targeting Lactate Dehydrogenase A (LDHA).
AB  - Osteosarcoma (OS) is one of the most common types of malignant bone tumor in
      adolescent. MicroRNAs (miRNAs) are widely studied regulatory molecules which play
      important roles in tumor development, differentiation, growth, invasion,
      chemosensitivity and cellular metabolism. Recently, miR-33b has been reported to
      act as a tumor suppressor in osteosarcoma. However, the detailed mechanism of miR
      33b in regulating osteosarcoma cell proliferation remains unclear. In this study,
      we detected miR-33b was significantly downregulated in osteosarcoma tissues
      compared to their matched adjacent nontumor tissues. The decreased expressions of
      miR-33b were also found in multiple osteosarcoma cell lines, including MG63, Saos
      2, U2OS and SOSP-9607 when compared to normal osteoblast cell line hFOB.
      Overexpression of miR-33b suppressed U2OS cell proliferation and anaerobic
      glycolysis. We identified Lactate dehydrogenase-A (LDHA) as a direct target of
      miR-33b in osteosarcoma tumors and cells by Western blot and luciferase assay.
      Moreover, inhibition of LDHA significantly suppressed glycolysis and cell
      proliferation of osteosarcoma cells. Restoration of LDHA in miR-33b
      overexpressing osteosarcoma cells reversed the suppressive effect of miR-33b on
      cell proliferation. In addition, we report a significantly negative correlation
      between LDHA mRNA and miR-33b expression in osteosarcoma tumors: miR-33b is
      downregulated in OS tumors with high levels of LDHA (92.9%). Meanwhile, high miR
      33b expressions were found majorly in OS tumors with low LDHA mRNA levels
      (82.4%). This study reveals that miR-33b plays a suppressive role in the
      regulation of osteosarcoma cell proliferation through direct targeting LDHA. The
      miR-33b/glycolysis/LDHA axis may contribute to development of therapeutic anti
      tumor agents for osteosarcoma.

PMID- 30213287
TI  - Screening for novel peptides specifically binding to the surface of ectopic
      endometrium cells by phage display.
AB  - A 7-mer phage display library was employed to isolate novel peptides that
      specifically bind to ectopic endometrium in vitro. Phage display technology with
      biopanning and rapid analysis of selective interactive ligands between ectopic
      and eutopic endometrium cells was utilized. After 5 rounds of biopanning, 50
      phage clones were randomly selected and analyzed by enzyme-linked immunosorbent
      assay and DNA sequencing. A peptide-competitive inhibition assay was performed to
      identify the affinity of positive phages toward ectopic endometrium cells. The
      most enriched polypeptide RTRLHTR showed higher affinity toward ectopic
      endometrium cells.The polypeptide RTRLHTR screened by phage display technology
      may offer a new direction for early diagnosis and treatment of endometriosis.

PMID- 30213288
TI  - Investigation of cochlear hair cells and the perception of ultrasound signals in
      guinea pigs.
AB  - We established a specific ultrasound frequency-dependent model of cochlear injury
      using bone conduction ultrasounds in the inner ear of guinea pigs at 50 kHz and
      83 kHz, to explore the effects of bone conduction ultrasound in the cochlea. To
      establish a unilateral cochlear damage model, the unilateral cochlea was
      destroyed. The control group consisted of 50 kHz and 83 kHz bone conduction
      ultrasounds in unaltered guinea pigs. In each group, cerebral blood oxygenation
      level dependent (BOLD) effects were determined by functional magnetic resonance
      imaging (fMRI). The cochlear outer hair cell motor protein, Prestin, and the
      microfilament protein, F-Actin, were detected. We found that bone conduction
      ultrasound irradiation at 50 kHz and 83 kHz on the guinea pig inner ear for six
      hours leads to hair cell damage. Furthermore, low frequency bone conduction
      ultrasound induces major damage to outer hair cells, while high frequency
      ultrasound damages both internal and external hair cells. fMRI analysis of
      cerebral BLOD effects revealed an affected cerebral cortex region of interest
      (ROI) of 4 and 2, respectively, for the normal control group at 50 kHz or 83 kHz,
      and 2 for the 83 kHz bone conduction ultrasound cochlear injury group, while 50
      kHz bone conduction ultrasound failed to induce the cortical ROI within injury
      model. Results reveal that the spatial location of guinea pig cochlear hair cells
      determines coding function for lower ultrasound frequencies, and high frequency
      bone conduction ultrasound may affect the cochlear spiral ganglion or cranial
      nerve nucleus in bone conduction ultrasound periphery perception.

PMID- 30213289
TI  - MiR-637 suppresses melanoma progression through directly targeting P-REX2a and
      inhibiting PTEN/AKT signaling pathway.
AB  - MicroRNAs (miRNAs) play important roles in melanoma. Although miR-637 has been
      suggested to be a tumor suppressor in several cancers, its function in melanoma
      and the molecular mechanism behind that function remain unclear. In this study,
      we investigated the role of miR-637 in human melanoma and explored its relevant
      mechanisms. We found that the expression of miR-637 is significantly
      downregulated in melanoma tissues and cell lines. While overexpression of miR-637
      inhibited melanoma cell proliferation and cell cycle G1-S transition, and induced
      apoptosis. Inhibition of miR-637 promoted cell proliferation and G1-S transition,
      and suppressed apoptosis. Subsequent investigation revealed that miR-637
      expression was inversely correlated with P-REX2a expression in melanoma tissues.
      P-REX2a was determined to be a direct target of miR-637 by using a luciferase
      reporter assay. Overexpression of miR-637 decreased P-REX2a expression at both
      the mRNA and protein levels, and suppression of miR-637 increased P-REX2a
      expression. Importantly, silencing P-REX2a recapitulated the cellular and
      molecular effects seen upon miR-637 overexpression, whereas, overexpression of P
      REX2a eliminated the effects of miR-637 overexpression on melanoma cells.
      Furthermore, both enforced expression of miR-637 or silencing of P-REX2a resulted
      in activation of PTEN, leading to a decline in AKT phosphorylation. Taken
      together, our study demonstrates that miR-637 inhibites melanoma cell
      proliferation by activation of AKT signaling pathway and induces apoptosis
      through regulation of Bcl-2/Bax expression via targeting P-REX2a. These findings
      suggest that miR-637 plays a crucial role in melanoma progression, and may serve
      as a potential novel target for melanoma therapy.

PMID- 30213290
TI  - Effect of hesperetin on inflammatory and oxidative status in trinitrobenzene
      sulfonic acid-induced experimental colitis model.
AB  - In our study, the effect of hesperetin on inflammatory and oxidative status in
      trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model was
      investigated through different methods. Eighteen Wistar albino male rats were
      divided in to three groups: Group I (Control, n = 8; 1 ml physiological saline),
      Group II (Colitis, n = 8; 1 ml TNBS), Group III (Hesperetin, n = 8; 1 ml TNBS and
      100 mg/kg hesperetin). Macroscopic and microscopic scores were calculated to
      determine the damage to the colon at the end of the experiment. Serum tumor
      necrosis factor-alpha (TNF-alpha) and tissue interleukin-6 (IL-6) levels were
      determined using the ELISA method. Myeloperoxidase (MPO), superoxide dismutase
      (SOD), catalase (CAT) and malondialdehyde (MDA) levels were investigated
      spectrophotometrically. The TUNEL method was used for the detection of apoptotic
      cells in the colon tissue. Inducible nitric oxide synthase (iNOS) and nuclear
      factor-kappa-B (NF-Kbeta) expression in the colon were determined
      immunohistochemically. Hesperetin administration has shown to significantly
      reduce levels of MPO, MDA, and proinflammatory agents (TNF-alpha, IL-6, and NF
      Kbeta). It has also been proven to inhibit mucosal apoptosis. This study
      indicates that hesperetin is protective against TNBS-induced colitis model via
      antiinflammatory, antioxidant and antiapoptotic effects.

PMID- 30213291
TI  - Expression profiles of proto-oncogene TWIST1 and tumor metastasis suppressor gene
      LASS2 in bladder cancer.
AB  - Transcription factor proto-oncogene TWIST1 and tumor metastasis suppressor gene
      LASS2 have been reported to be involved in various carcinomas but their
      expression profiles and prognostic significances in bladder cancer are largely
      unknown. We aimed to determine these genes' expression levels both at mRNA and
      protein level in bladder cancer. mRNA expression levels of TWIST1 and LASS2 genes
      were examined using real-time quantitative PCR (qPCR) in human bladder tumors and
      paired normal adjacent tissues obtained from 44 patients. Protein expression
      profiles of both genes were detected by immunohistochemical staining in formalin
      fixed and paraffin-embedded tissues from the same patients. The expression
      profiles of TWIST1 mRNA in bladder tumors were significantly lower than the
      normal adjacent tissues and linked to both the stage and the grade. The
      expression profiles of LASS2 mRNA in bladder tumors were also significantly lower
      than the normal adjacent tissues reflecting the potential tumor suppressor
      profile of the gene, independently from stage or grade. By immunohistochemistry,
      TWIST1 and LASS2 positive expression rates were found as 14.3% (6/42) and 38.1%
      (16/42), respectively. As potential molecular markers for bladder carcinoma, both
      TWIST1 and LASS2 transcripts seem to play role during the tumorigenesis and
      development of bladder cancer. Lack of a functional link and/or weak inverse link
      between TWIST1 and LASS2 transcripts and immunohistochemical findings may reflect
      the potential associations of transcription regulation mechanisms and merit
      further investigations. To the best of our knowledge, this is the first report
      investigating the combined expression profile of TWIST1 and LASS2 in bladder
      cancer both at mRNA and protein level.

PMID- 30213292
TI  - The effects of apelin on myometrium contractions in pregnant rats.
AB  - Apelin, which is a new hormone, is secreted especially in the brain by
      hypothalamus as well as by many other organs like the stomach, fat tissue, and
      the heart. For apelin, whose possible effects on many bodily functions like the
      endocrine system, cardiovascular system and metabolic activities are still under
      investigation, the reproductive system is also an important target area. The
      purpose of the present study was to investigate the effects of plasma apelin
      levels in rats that were in diestrus, pregnancy and lactation periods, and to
      examine its possible effects on myometrium contractions of pregnant rats and non
      pregnant rats that were in diestrus period.  The plasma apelin concentrations in
      female adult Wistar rats were determined with the ELISA method in the diestrus
      period, and on the 12th, 18th, and 21st days of the pregnancy, and on the 2nd and
      10th days of lactation (n=7 for each group). In addition, the effect of apelin at
      0.01, 0.1, 1 and 10 MUM doses on isometric contractions in the rat uterus on the
      21st day of pregnancy and in diestrus period was tested by using isolated organ
      bath. This protocol was repeated under conditions that were pre-treated with
      protein kinase C inhibitor in calcium-free medium, and the possible effect of
      apelin on contractions and the mechanisms that might mediate this effect were
      investigated. When plasma apelin levels were compared with the rats in diestrus
      period, the apelin concentrations in the 21-day pregnancy group were high at a
      significant level (p<0.05); and low at a significant level in the 2-day lactation
      group (p<0.05). In myometrium contraction trials, it was observed that apelin
      induced the contractions. Apelin increased the frequency of the myometrium
      contractions at a significant level when applied at 1 MUM and 10 MUM
      concentrations (p<0.05 and p<0.001). Only after the apelin application at 10 MUM
      concentration did the amplitude of the contractions increase at a significant
      level (p<0.01). In the myometrium of the rats that were on the 21st day of
      pregnancy, the frequency of the contractions was statistically significant at 0.1
      MUM, 1 MUM and 10 MUM doses (p<0.01). In addition, the amplitude of the
      contractions increased at a statistically significant level at 1 MUM and 10 MUM
      dose application (p<0.05 and p<0.01, respectively). The apelin application
      induced the contractions in calcium-free medium. When apelin was applied after
      the pre-application with protein kinase C inhibitor, no contractions were
      observed. The present study showed that apelin levels were increased at the end
      of pregnancy in rats, and the hormone induced the uterus contractions. This
      effect does not occur with protein kinase C inhibitor and in calcium-free medium,
      which shows that protein kinase C pathway might play a role in these mechanism. 
      These findings show that apelin might be an endogenous peptide that plays a role
      on uterine contractions at birth in rats.

PMID- 30213293
TI  - Effect of GDF11 on proliferation and apoptosis of esophageal cancer cells.
AB  - This study was aimed at investigating the effect of growth differentiation factor
      11 (GDF11) on the proliferation and apoptosis of esophageal cancer cells. Serum
      levels of GDF11 in esophageal cancer patients were determined with ELISA kits,
      and the correlation between serum GDF11 and pathological features of esophageal
      cancer were determined. The effect of recombinant GDF11 on the growth of
      esophageal cancer cells was measured by CCK6 method. In order to investigate the
      effect of recombinant GDF11 on the proliferation and apoptosis of esophageal
      cancer cells, the expression of apoptosis-promoting protein Bax and proliferative
      associated protein Bcl-2 in esophageal cancer cells were determined using western
      blot. Moreover, GDF11 was used to treat esophageal cancer cells, and its effect
      on proliferation and apoptosis was determined with MTT assay and flow cytometry,
      respectively. The serum content of GDF11 was much less in esophageal cancer
      patients than in the control group. Esophageal GDF II in cancer patients was
      correlated with cancer differentiation: the higher the degree of differentiation,
      the higher the content of GDF11. GDF11 inhibits proliferation and apoptosis of
      esophageal cancer cells.

PMID- 30213294
TI  - -174 G/C polymorphism of interleukin 6 gene is not significantly different in
      Turkish professional short and long distance runners.
AB  - Interleukin-6 (IL-6) is a kind of multifunctional cytokine and involved in
      mediating muscle repair metabolism, and therefore athletic capacity.  Muscular
      and circulating IL-6 levels increase in response to physical exercise.
      Responsible gene coding for IL-6 has a functional polymorphism in its promoter
      region, -174 G/C (rs1800795). We aimed to analyze the association of G allele and
      GG genotype in Turkish professional athletes and compare the allelic and
      genotypic difference between short distance and long distance runners. For this
      purpose, we enrolled 40 (24 short distance runners and 16 long distance runners)
      Turkish professional athletes to the study. Real time genotyping procedure was
      carried out to determine the -174 G/C polymorphism. G allele and GG genotype was
      more prevalent than the others in our cohort. We found no statistically
      significant difference between short and long distance runners in the terms of
      genotype (p=0.07). Our study suggests that-174 G/C polymorphism of IL-6 gene
      differs in athletes, G allele and GG genotype is higher than the other ones, at
      least in Turkish athletes, and therefore should be taken into consideration when
      determining genetic aspects of athletes. Further studies are necessary to confirm
      our results and show the effect of the given polymorphism in sports science.

PMID- 30213295
TI  - Contrast enhanced ultrasound in diagnosis of endometrial carcinoma and
      endometrial hyperplasia.
AB  - The present study was aimed to compare application of contrast enhanced
      ultrasound (CEUS) in diagnosis of endometrial carcinoma (EC) and endometrial
      hyperplasia (EH). A total of 81 patients with EC and simple EH were selected in
      this study. Among all patients, 39 cases were diagnosed as EC and 42 cases were
      diagnosed with EH. All patients were diagnosed by CEUS examination. The diagnosis
      of EC and EH was also confirmed by endometrial biopsy. CEUS was conducted for all
      patients. Eendometrial thickness was measured and the mean arrival time, time-to
      peak, enhancement time, arrival intensity, peak intensity, enhancement intensity,
      rising rate, washout half-time and clearance half-time were recorded. Myometrial
      invasion was categorized into 2 stages <50% and >50%. No significant difference
      was observed in clinical basis between the two groups. Endometrial thickness of
      EC was significantly higher than that of EH, P<0.05. Results of CEUS parameters
      showed that in EC patients, all values of arrival time, time-to-peak, washout
      half-time and clearance half-time were all shorter in EC group compared with
      those in EH patients, P<0.05. And values of peak intensity, enhancement
      intensity, and rising rate were also lower in EC patients than those in EH
      patients, P<0.05. Diagnostic accuracy of CEUS in myometrial invasion for EC was
      shown showed that 26 of 30 cases were diagnosed as myometrial invasion <50% by
      CEUS and 7 of 9 cases were diagnosed as myometrial invasion >50%. The total
      diagnostic accuracy of CEUS is 82.62% (33/39). We conducted a comparison study to
      analyze different diagnostic effects of CEUS for EC and EH. The study may give
      more clinical basic data in the field of CEUS application in diagnosis of EC and
      can give a reference to the difference between EC and EH.

PMID- 30213296
TI  - CTLA-4 (+49A/G) and NOD2/CARD15 (N852S) polymorphisms with inflammatory bowel
      disease in Turkish patients.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are the major types of
      inflammatory bowel disease (IBD) and exhibit similar clinical features and
      epidemiology. The main objective of this study was to analyze the correlation
      between the CTLA-4 gene +49A/G polymorphism and the NOD2/CARD15 gene N852S
      polymorphism in Turkish patients with IBD using polymerase chain reaction and
      restriction fragment length polymorphism (PCR-RFLP) analysis. In this study, we
      evaluated the frequency of the CTLA-4 (+49A/G) and NOD2/CARD15 (N852S)
      polymorphisms in 62 patients with CD, 76 patients with UC, and 152 healthy
      individuals. The CTLA-4 and NOD2/CARD15 variants, rs231775 and rs104895467, were
      genotyped by PCR followed by RFLP. The results for the patients and the control
      group were statistically analyzed. According to our results, the CTLA-4 gene
      +49A/G polymorphism AA genotype was prevalent in CD patients and controls (29% vs
      40%); the AG (56% vs 51%) and GG (15% vs 9%) genotypes were also observed. The
      prevalence of the of AA, AG and GG genotypes for the +49A/G polymorphism was 56%,
      32% and 12%, respectively, in the UC patients, and 40%, 51% and 9%, respectively,
      in the healthy controls. In all subjects, just one band of 151 bp, corresponding
      to wild-type N852S, was found, and no other N852S mutant bands (151+129+22 and
      129+22 bp) were detected using PCR-RFLP fragment electrophoresis.The CTLA-4 gene
      +49 A/G polymorphism and the NOD2/CARD15 gene N852S polymorphism were not
      associated with CD or UC in a Turkish population.

PMID- 30213297
TI  - Piperlongumine as anticancer agent: The story so far about killing many birds
      with one stone.
AB  - Piperlongumine is a biologically and pharmacologically active constituent of the
      plant Piper longum. This compound is gradually gaining attention because of its
      ability to inhibit/prevent different cancers. Modern era of molecular oncology is
      incomplete without ground-breaking discoveries made in the field of cell
      signaling pathways. High-throughput technologies have considerably improved our
      understanding about wide ranging signal transduction cascades which play crucial
      role in cancer development and progression. It is exciting to note that
      piperlongumine has been shown to pleiotropically modulate different oncogenic
      signaling pathways. We partition this multi-component review into discrete
      sections and categorically summarize key findings related to excellent ability of
      piperlongumine to therapeutically target JAK-STAT, NF-kB and PI3K/AKT/mTOR
      pathways. We also set spotlight on regulation of TRAIL pathway and autophagy by
      piperlongumine in different cancers. On the basis of the current understanding of
      piperlongumine, molecular biologists and pharmacologists will develop the next
      generation of translational studies, which will prove to be helpful in improving
      the clinical outcome and getting a step closer to personalized medicine.

PMID- 30213298
TI  - The influence of dimethyl sulfoxide (DMSO) on metabolic activity and morphology
      of melanoma cell line WM-266-4.
AB  - Dimethyl sulphoxide (DMSO) is widely used as a solvent in biomedical research,
      regularly in concentrations up to 1%. Nevertheless, little is known about the
      effect of different DMSO concentration on WM-266-4 metastatic melanoma cells,
      which are often used in melanoma research. Due to resistance of melanoma cells
      high concentrations of cytotoxic substances soluble in DMSO are used in vitro
      tests. Consequently, total DMSO concentration often exceeds 1%. The aim of our
      study was to test the metabolic activity and morphology of WM-266-4 cells exposed
      to selected DMSO concentrations for different period of time. Cells were
      incubated in selected ethanol concentrations for comparison. MTT test was
      performed to determine proliferation activity of the cells and morphological
      analysis was carried out by phase-contrast microscopy. Our results show
      inhibitory effect of DMSO on WM-266-4 cells' metabolic activity. Morphology of
      the cells changed progressively with the time of exposure. Ethanol showed little
      effect on metabolic activity of the cells and no effect on cell morphology after
      selected period of time. According to our study, for specific in vitro tests
      concentrations of DMSO up to 1.5% may be appropriate for WM-266-4 cell line
      experiments.

PMID- 30213299
TI  - Association between BIM polymorphism and lung cancer outcomes: a meta-analysis.
AB  - Accumulating evidences have indicated that BIM expression largely decides the
      development of lung cancer and outcome of EGFR-mutant lung cancers after TKI
      treatments. BIM polymorphism is a 2,903-bp deletion in the second exon. To
      clarify the relationship between this BIM polymorphism and clinical outcomes of
      lung cancers, we conducted this meta-analysis and observed the survival and
      responses to TKIs. Sixteen cohort studies, covering 4393 WT and 916 BIM deletion
      patients were included. Overall, BIM deletion polymorphism was associated with
      significantly shorter progression-free survival (PFS) and slightly shorter
      overall survival (OS), compared to the WT group. Moreover, patients with BIM
      deletion polymorphism showed significantly inferior response to EGFR TKIs. In
      conclusion, our analysis confirmed that lung cancer patients harboring the BIM
      deletion have inferior survival and TKI responses. Examination of the novel
      biomarker BIM deletion in lung cancer patients, especially for the EGFR mutant
      cohort, could provide some prognostic utility.

PMID- 30213300
TI  - [Semen quality and fertility: the role of the environment and health].
AB  - Sperm quality appears to be degrading over the past 40 years. Nowadays, more than
      35 % of causes of male infertility are still idiopathic. More and more studies
      have suggested an impact of environment on sperm quality, essentially through
      epigenetic and hormonal changes. Recent studies in men with impaired sperm
      quality, have demonstrated epigenetic variations in sperm DNA. These
      modifications are responsible for modifications of the expression of
      transmissible genes to theiroffspring. Those transgenerational effects have been
      particularly illustrated in drosophila and caenorhabditis elegans. In humans,
      consequences of the environment on fertility have been studied in obese men, who
      present hypogonadotropic as well as hypergonadotropic hypogonadisms.
      Interestingly, recent studies have suggested a correlation between sperm quality
      and longevity. In summary, those environmental factors are the source of new
      causes of infertility.

PMID- 30213302
TI  - [Differences of Sex Development (DSD): Controversies and Challenges].
AB  - DSD for "Differences of Sex Development" or "Sexual Differences Development"
      refers to situations where chromosomal, gonadal or anatomical sex is atypical.
      DSD 46,XX are mainly represented by congenital adrenal hyperplasia (HCS) and are
      not a diagnostic issue. DSD 46,XY involve genes for the determination and
      differenciation of the bipotential gonad, making sometimes difficult the choice
      of sex at birth. They remain without diagnosis in about half of the cases,
      despite the new genetic techniques (exome, NGS). The management of DSD is complex
      as well as are the long-term consequences, particularly in terms of options for
      medical or surgical treatments, fertility and quality of life of patients that
      should be discussed. This review describes the main causes of DSD and the recent
      issues of their clinical management. It addresses the difficult question of
      identity of these patients, in a society that leaves no place for difference.

PMID- 30213301
TI  - [Hereditary pheochromocytoma and paraganglioma: screening and follow-up
      strategies in asymptomatic mutation carriers].
AB  - The management of pheochromocytoma and paraganglioma has deeply evolved over the
      last years due to the discovery of novel genes of susceptibility, especially
      SDHx, MAX and TMEM127. While the modalities of diagnosis and management of
      patients presenting with hereditary pheochromocytoma and paraganglioma are now
      well defined, screening and follow-up strategies for asymptomatic mutation
      carriers remain a matter of debate. This raises major questions as these
      asymptomatic patients will require a lifelong follow-up. The aim of this review
      is an attempt to give insights on the optimal screening and follow-up strategies
      of asymptomatic carriers of SDHx, MAX and TMEM127 mutations, with additional
      thoughts on the forensic and psychological aspects of the management of such
      patients with rare diseases.

PMID- 30213303
TI  - [New perspectives for the diagnosis and prognosis of Graves' disease].
AB  - Graves' thyroiditis is a frequent disease. It has a considerable impact on
      patient's life quality and health expenses. Thus, it is important to optimize the
      treatment and follow up. The identification of new factors predisposing to the
      disease and factors that may help to predict the severity or recurrence of the
      disease or the occurrence of graves' orbitopathy could optimize the management.
      Genetic predisposition has a major role in the development of Graves' disease.
      The new genes in addition to those already known to be involved in Graves'
      disease are under study. However, genetic predisposition alone cannot explain the
      occurrence of the disease. MicroRNAs are non-genetic factors that are
      significantly associated with different severities or relapses of Graves' disease
      as well as with the occurrence of graves' orbitopathy. These genetic and
      epigenetic factors together with known environmental factors can be used to
      predict the risk of relapse of Graves' disease or of the occurrence of orbital
      orbitopathy. This will lead to new promising therapeutic targets.

PMID- 30213305
TI  - Special Issue Introduction.

PMID- 30213304
TI  - [Bone and metabolism].
AB  - Bone is now considered as a particular endocrine organ. Its endocrine function is
      not yet fully understood and has been the subject of several conferences at the
      European Society of Endocrinology Congress 2018. Bone regulates phosphate
      metabolism by secreting fibroblast growth factor 23; it also regulates glucose
      metabolism via osteocalcin and energy metabolism, thanks to lipocalin 2, a new
      hormone acting on the brain. In addition, the incidence of diabetes continues to
      grow, and its impact on bone has been demonstrated, with an increased risk of
      fractures regardless the type of diabetes. The mechanism of bone fragility in
      this disease is not fully known but it involves a decrease in bone turnover and
      bone demineralization. Recent findings on the role of bone on glucose and mineral
      metabolism could open therapeutic perspectives, especially for the treatment of
      diabetes or obesity.

PMID- 30213306
TI  - ?

PMID- 30213307
TI  - [Topical application of analgesic cream for spinal anaesthesia in elective
      orthopaedic surgery].
AB  - Lidocaine-Prilocaine (Emla(r)) analgesic cream is commonly used for pain relief
      during puncture in patients receiving spinal anaesthesia. The protocols for this
      procedure vary widely. A study was conducted in elective orthopaedic surgery to
      determine the factors influencing the quality of application and those that
      improve it.

PMID- 30213308
TI  - [Screening for sepsis, the central role of the nurse].
AB  - In 2016, the International Consensus Conference 'Sepsis-3' highlighted the value
      of Sequential Organ Failure Assessment (SOFA) and Quick Sequential Organ Failure
      Assessment (qSOFA) scores in addition to medical and paramedical clinical
      reasoning to assess severity and the risk of mortality. The option of using qSOFA
      scores in healthcare services underlines the important role of nurses in the
      early detection of sepsis with a risk of unfavourable outcome, raising hopes of
      reducing the associated mortality.

PMID- 30213309
TI  - ?

PMID- 30213310
TI  - [Semantics, epidemiology and semiology of stroke].
AB  - Stroke is a cerebrovascular disorder characterised by the sudden onset of
      symptoms and clinical signs. Each year, an estimated 140,000 people in France are
      hospitalised for stroke. Ischemic stroke is the most common kind of stroke,
      accounting for 80% of all cases. Haemorrhagic stroke accounts for about 20% of
      all strokes.

PMID- 30213311
TI  - [Acute phase of stroke: every minute counts].
AB  - Cerebral infarction (CI) is caused by intracranial artery occlusion. The main
      treatment approach is recanalisation, which is performed either medically, by
      intravenous thrombolysis within 4 hours and a half of the event, or by mechanical
      thrombectomy, which is possible up to 24 hours after CI.

PMID- 30213312
TI  - ?

PMID- 30213313
TI  - [Role of pre-hospital and hospital emergency services in the management of
      stroke].
AB  - Any out-of-hospital neurological deficit of less than 24 hours should prompt a
      call for emergency medical help Urgent Medical Aid Service. Early identification
      of signs of stroke or transient ischaemic attack allows to guide the therapeutic
      approach towards intravenous thrombolysis or other alternatives. Telemedicine
      centres complement the network of neurovascular units.

PMID- 30213314
TI  - [Nursing support during thrombolysis in the neurovascular ICU].
AB  - Intravenous thrombolysis is one of two emergency procedures for ischaemic stroke.
      Its implementation requires fine coordination of the healthcare team and must be
      adapted to the local context of each hospital and sector. International good
      clinical practice guidelines are available to support team organisation.

PMID- 30213315
TI  - [Nursing care after thrombectomy].
AB  - Since its inception in 2015, thrombectomy has revolutionised the emergency
      management of ischaemic stroke with large vessel occlusion. Indeed, early
      endovascular extraction of the thrombus considerably improves the prognosis.
      Different medical teams are involved in the critically urgent management of these
      very fragile patients.

PMID- 30213316
TI  - [Multidisciplinary management in the first few hours after treatment of a
      stroke].
AB  - The first 24 hours of post-treatment management of stroke in a neurovascular unit
      are critical. Combined assistance from nurses, nursing assistants and
      physiotherapists ensures patient safety, preventing complications and recurrence
      and allowing prompt initiation of rehabilitation therapy. Multidisciplinary
      management focuses on patients and their specific needs based on values shared by
      all members of the team.

PMID- 30213317
TI  - [A fun information tool for patients after a stroke].
AB  - "L'ABC de l'AVC(r)" [A complete guide to stroke] is a fun information tool
      created for stroke patients by the multidisciplinary team of a neurovascular
      unit. It is designed to improve patient knowledge of the disease, its causes and
      consequences, preparing them to better understand what the future holds. It also
      serves as a training tool for professionals.

PMID- 30213318
TI  - [Psychological rehabilitation after stroke].
AB  - Stroke often causes psychological trauma as a result of dealing with serious,
      life-threatening disease. While each patient reacts differently, conversion
      disorders such as sideration are commonly observed. These can be managed by
      resilient psychological rehabilitation therapy with the various caregivers.

PMID- 30213319
TI  - ?

PMID- 30213320
TI  - [Peer network for the therapeutic education of patients with type 2 diabetes in
      Mali].
AB  - Despite numerous health challenges, African healthcare systems are faced with
      limited financial and human resources. In this context, the epidemiological
      transition witnessing an explosion in the prevalence of non-communicable
      diseases, particularly diabetes, there are tremendous challenges to be met. Given
      the lack of human resources in these health systems, therapeutic education relies
      on networks of trained peer educator patients who also provide significant
      psychosocial support.

PMID- 30213321
TI  - ?

PMID- 30213323
TI  - Has the SYNTAX Score Become Obsolete?

PMID- 30213322
TI  - Prognostic Value of the Residual SYNTAX Score After Functionally Complete
      Revascularization in ACS.
AB  - BACKGROUND: The residual SYNTAX (Synergy Between Percutaneous Coronary
      Intervention With Taxus and Cardiac Surgery) score (RSS) quantitatively assesses
      angiographic completeness of revascularization after percutaneous coronary
      intervention (PCI) and has been shown to be a predictor of events after
      angiography-guided PCI. In stable patients undergoing functionally complete
      revascularization with fractional flow reserve (FFR) guidance, RSS did not
      predict outcome. Whether this is also true in patients with acute coronary
      syndromes (ACS) is unknown. OBJECTIVES: The purpose of this study was to
      determine whether the RSS could predict outcomes in patients with ACS. METHODS:
      From the DANAMI-3-PRIMULTI (Primary PCI in Patients With ST-elevation Myocardial
      Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete
      Revascularization), FAME (Fractional Flow Reserve Versus Angiography for
      Multivessel Evaluation), and FAMOUS-NSTEMI (Fractional Flow Reserve Versus
      Angiographically Guided Management to Optimise Outcomes in Unstable Coronary
      Syndromes) trials, 547 patients presented with ACS and underwent functionally
      complete revascularization. Major adverse cardiac events (MACE) were defined as
      the composite endpoint of all-cause death, nonfatal myocardial infarction, and
      any repeat revascularization. The RSS was based on the recalculation of the
      SYNTAX score after PCI. We compared differences in 2-year outcome by the RSS
      subgroups: 0, 1 to <5, 5 to <10, >=10 (RSS = 0 represents angiographically
      complete revascularization). RESULTS: The study population consisted of 271
      patients with unstable angina/non-ST-segment elevation myocardial infarction and
      276 with ST-segment elevation myocardial infarction. The mean RSS was 6.7 +/-
      5.8. MACE at 2 years occurred in 69 patients (12.6%). Patients with and without
      MACE had similar RSS after PCI (RSS: 7.2 +/- 5.5 vs. 6.6 +/- 5.9; p = 0.23).
      Kaplan-Meier curve analysis showed a similar incidence of MACE regardless of the
      RSS subgroups (p = 0.54). With and without adjustment of clinical variables, RSS
      was not a significant predictor of MACE or of each component of MACE.
      CONCLUSIONS: After complete revascularization of functionally significant
      stenosis by FFR, the extent of residual angiographic disease is not associated
      with subsequent ischemic events in patients presenting with ACS. These results
      suggest that the concept of functionally complete revascularization is applicable
      even in ACS patients. (Fractional Flow Reserve Versus Angiography for Multivessel
      Evaluation [F.A.M.E.] NCT00267774; Fractional Flow Reserve Versus
      Angiographically Guided Management to Optimise Outcomes in Unstable Coronary
      Syndromes [FAMOUS NSTEMI] NCT01764334; Primary PCI in Patients With ST-elevation
      Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only
      or Complete Revascularization [DANAMI-3-PRIMULTI]; NCT01960933).

PMID- 30213324
TI  - 21-Year Survival of Left Internal Mammary Artery-Radial Artery-Y Graft.
AB  - BACKGROUND: In 1999, Royse et al. reported on the left internal mammary artery,
      radial artery, Y-graft technique (LIMA-RA-Y), which achieves total arterial
      revascularization (TAR). However, the most common coronary reconstruction remains
      LIMA and supplementary saphenous vein grafts (LIMA + SVG). OBJECTIVES: The goal
      of this study was to conduct a survival comparison of LIMA-RA-Y versus the
      conventional LIMA + SVG. METHODS: Of the original 464 LIMA-RA-Y patients reported
      (1996 to 1998), 346 were from the Royal Melbourne Hospital. Survival at June 2017
      was compared with a group of 534 patients from 1996 to 2003 from the same
      institution who received LIMA + SVG, or 5,800 patients who received TAR with
      different grafting configurations. Propensity score matching (PSM) was performed
      with 1:1 matching using 26 variables. Comparisons used Kaplan-Meier (KM) and Cox
      proportional hazards methods. LIMA-RA-Y was compared with LIMA + SVG in which all
      non-left anterior descending artery grafts were performed with either composite
      RA or aorta-coronary SVG with no use of right internal mammary artery. We also
      conducted a comparison of LIMA-RA-Y versus TAR. RESULTS: Baseline characteristics
      of the LIMA-RA-Y group (n = 346) compared with LIMA + SVG (n = 534) after PSM (n
      = 232 pairs) did not differ (3.3 +/- 0.8 grafts per patient). Survival was worse
      for LIMA + SVG in the unmatched groups (KM, p < 0.001) and for PSM groups (KM, p
      = 0.043; Cox proportional hazards ratio: 1.3; 95% confidence interval: 1.0 to
      1.6; p = 0.038). Survival did not differ between LIMA-RA-Y and other TAR (n =
      5,800) patients before, or after, PSM (n = 332 pairs). CONCLUSIONS: Use of LIMA +
      SVG has worse survival than LIMA-RA-Y in achieving total arterial
      revascularization.

PMID- 30213325
TI  - Total Arterial Revascularization for Coronary Artery Bypass: A Gold Standard
      Searching for Evidence and Application.

PMID- 30213326
TI  - Epicardial Left Atrial Appendage Exclusion Reduces Blood Pressure in Patients
      With Atrial Fibrillation and Hypertension.
AB  - BACKGROUND: Percutaneous left atrial appendage exclusion (LAAE) has evolved as an
      alternative strategy for stroke prevention in atrial fibrillation (AF). Recent
      observational data have suggested that epicardial LAAE can have substantial
      impact on arrhythmia burden and hemodynamic profile. OBJECTIVES: The authors
      aimed to study the impact of epicardial versus endocardial LAAE on systemic blood
      pressure in hypertensive AF patients. METHODS: This was a prospective,
      nonrandomized study comparing 247 patients who underwent epicardial LAAE with 124
      patients with endocardial exclusion. Clinical outcomes were measured at 3 months
      and 1 year. Primary outcome was improvement in systolic blood pressure (SBP)
      between both groups compared with baseline. Secondary outcome included changes in
      diastolic pressures (DBP), serum electrolytes, and creatinine. RESULTS: There was
      no significant difference in baseline SBP between epicardial and endocardial
      groups. SBP was significantly lower in the epicardial group both at 3 months (122
      +/- 11.8 mm Hg vs. 129.7 +/- 8.2 mm Hg; p < 0.001) and 1 year (123 +/- 11.6 mm Hg
      vs. 132.2 +/- 8.8 mm Hg; p < 0.001) compared with the endocardial group. An
      adjusted multivariate linear mixed effects model demonstrated that epicardial
      LAAE significantly decreased SBP by 7.4 mm Hg at 3 months and by 8.9 mm Hg at 1
      year (p < 0.0001). There was a trend toward lower DBP with epicardial LAAE at 3
      months by 1.3 mm Hg (p = 0.2) and at 1 year by 1.8 mm Hg (p = 0.09). There was no
      significant difference in serum electrolytes and creatinine between both groups.
      CONCLUSIONS: In hypertensive AF patients, epicardial LAAE significantly decreases
      SBP both at 3 and 12 months compared with endocardial exclusion.

PMID- 30213327
TI  - The Lariat Device: R.I.P. or Buried Alive.

PMID- 30213328
TI  - Outcomes Among Patients With Atrial Fibrillation and Appropriate Anticoagulation
      Control.
AB  - BACKGROUND: Atrial fibrillation (AF) patients on a vitamin K antagonist (VKA)
      with time in therapeutic range (TTR) >=70% are not recommended to switch to a
      direct oral anticoagulant according to guidelines. OBJECTIVES: This study sought
      to assess future TTR and risk of stroke/thromboembolism and major bleeding among
      AF patients on VKA with TTR >=70%. METHODS: The authors used Danish nationwide
      registries to identify AF patients on VKA from 1997 to 2011 with available
      international normalized ratio values. Patients were included 6 months after VKA
      initiation, divided according to TTR, and followed for 12 months after inclusion.
      Cox proportional hazard models estimated hazard ratios (HRs). TTR was examined
      both as a baseline variable and as a time-dependent covariate in the Cox models.
      RESULTS: Of the 4,772 included AF patients still on VKA 6 months after
      initiation, 1,691 (35.4%) had a TTR >=70%, and 3,081 (65.6%) had a TTR <70%.
      Among patients with prior TTR >=70% still on treatment 12 months after inclusion,
      only 513 (55.7%) still had a TTR >=70%. Compared with prior TTR >=70%, prior TTR
      <70% was not associated with a higher risk of stroke/thromboembolism (HR: 1.14;
      95% confidence interval [CI]: 0.77 to 1.70) or major bleeding (HR: 1.12; 95% CI:
      0.84 to 1.49). When the authors estimated TTR time-dependently during follow-up,
      TTR <70% was associated with an increased risk of stroke/thromboembolism (HR:
      1.91; 95% CI: 1.30 to 2.82) and major bleeding (HR: 1.34; 95% CI: 1.02 to 1.76).
      CONCLUSIONS: Among AF patients on VKA, almost one-half of patients with prior TTR
      >=70% had TTR <70% during the following year. Prior TTR >=70% per se had limited
      long-term prognostic value.

PMID- 30213329
TI  - Should We Switch Patients Who Appear to Be Optimally Anticoagulated on Warfarin
      to DOACs?

PMID- 30213330
TI  - Oral Fluoroquinolone and the Risk of Aortic Dissection.
AB  - BACKGROUND: Previous studies raised safety concerns on the association between
      fluoroquinolone treatment and serious collagen disorders, aortic aneurysm and
      dissection (AA/AD). OBJECTIVES: This study sought to evaluate this association
      via a case-crossover analysis in a large national administrative database.
      METHODS: A case-crossover design was used to compare the distributions of
      fluoroquinolone exposure for the same patient across a 60-day period before the
      AA/AD event (hazard period) and 1 randomly selected 60-day period (referent
      period) between 60 to 180 days before the AA/AD events. In the sensitivity
      analysis, the authors repeated the main analysis using a 1:5 ratio of hazard
      period to referent period, to adjust for the effect of time-variant confounders.
      A disease-risk score-matched time control analysis was performed to investigate
      the potential time-trend bias. The risks were calculated by a conditional
      logistic regression model. RESULTS: A total of 1,213 hospitalized AA/AD patients
      were identified between 2001 and 2011. In the main case-crossover analysis,
      exposure to fluoroquinolone was more frequent during the hazard periods than
      during the referent periods (1.6% vs. 0.6%; odds ratio [OR]: 2.71; 95% confidence
      interval [CI]: 1.14 to 6.46). In the sensitivity analysis, after adjustment for
      infections and co-medications, the risk remains significant (OR: 2.05; 95% CI:
      1.13 to 3.71). An increased risk of AA/AD was observed for prolonged exposure to
      fluoroquinolones (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day
      exposure). Susceptible period analysis revealed that the use of fluoroquinolone
      within 60 days was associated with the highest risk of AA/AD. In the case-time
      control analysis, there was no evidence that the observed association is due to
      temporal changes in fluoroquinolone exposure. CONCLUSIONS: Exposure to
      fluoroquinolone was substantially associated with AA/AD. This risk was modified
      by the duration of fluoroquinolone use and the length of the hazard period.

PMID- 30213331
TI  - Do Fluoroquinolones Increase the Risk of Aortic Aneurysms and Aortic Dissection?

PMID- 30213332
TI  - Positive Psychological Well-Being and Cardiovascular Disease: JACC Health
      Promotion Series.
AB  - Facets of positive psychological well-being, such as optimism, have been
      identified as positive health assets because they are prospectively associated
      with the 7 metrics of cardiovascular health (CVH) and improved outcomes related
      to cardiovascular disease. Connections between psychological well-being and
      cardiovascular conditions may be mediated through biological, behavioral, and
      psychosocial pathways. Individual-level interventions, such as mindfulness-based
      programs and positive psychological interventions, have shown promise for
      modifying psychological well-being. Further, workplaces are using well-being
      focused interventions to promote employee CVH, and these interventions represent
      a potential model for expanding psychological well-being programs to communities
      and societies. Given the relevance of psychological well-being to promoting CVH,
      this review outlines clinical recommendations to assess and promote well-being in
      encounters with patients. Finally, a research agenda is proposed. Additional
      prospective observational studies are needed to understand mechanisms underlying
      the connection between psychological well-being and cardiovascular outcomes.
      Moreover, rigorous intervention trials are needed to assess whether psychological
      well-being-promoting programs can improve cardiovascular outcomes.

PMID- 30213333
TI  - Rheumatic Heart Disease Worldwide: JACC Scientific Expert Panel.
AB  - Rheumatic heart disease (RHD) is a preventable heart condition that remains
      endemic among vulnerable groups in many countries. After a period of relative
      neglect, there has been a resurging interest in RHD worldwide over the past
      decade. In this Scientific Expert Panel, the authors summarize recent advances in
      the science of RHD and sketch out priorities for current action and future
      research. Key questions for laboratory research into disease pathogenesis and
      epidemiological research on the burden of disease are identified. The authors
      present a variety of pressing clinical research questions on optimal RHD
      prevention and advanced care. In addition, they propose a policy and
      implementation research agenda that can help translate current evidence into
      tangible action. The authors maintain that, despite knowledge gaps, there is
      sufficient evidence for national and global action on RHD, and they argue that
      RHD is a model for strengthening health systems to address other cardiovascular
      diseases in limited-resource countries.

PMID- 30213334
TI  - Professor Sir Magdi Yacoub and the Aswan Heart Centre.

PMID- 30213335
TI  - ABIM/ACC Competency-Based Education Pilot in Internal Medicine-Cardiology: A
      Fellow's Perspective.

PMID- 30213336
TI  - RESPONSE: Are We Ready for Competency-Based Cardiology Training?

PMID- 30213337
TI  - Prognosis in Patients With Diabetes Mellitus and STEMI Undergoing Primary PCI.

PMID- 30213338
TI  - Noncardiac Production of Soluble ST2 in ST-Segment Elevation Myocardial
      Infarction.

PMID- 30213339
TI  - 50 Years From Bench to Bedside: His Bundle Pacing Versus Right Ventricular Apical
      Pacing.

PMID- 30213340
TI  - Reply: 50 Years From Bench to Bedside: His Bundle Pacing Versus Right Ventricular
      Apical Pacing.

PMID- 30213341
TI  - Inflammatory Pathways in CVD and Diabetes: Broad-Spectrum Versus Selective
      Targeting.

PMID- 30213342
TI  - Reply: Inflammatory Pathways in CVD and Diabetes: Broad-Spectrum Versus Selective
      Targeting.

PMID- 30213343
TI  - The Smartwatch Will See You Now: Implications of Mass Screening for Atrial
      Fibrillation.

PMID- 30213344
TI  - Reply: The Smartwatch Will See You Now: Implications of Mass Screening for Atrial
      Fibrillation.

PMID- 30213345
TI  - Correction.

PMID- 30213346
TI  - Recognizing the Relationship Between Disorders in the Oral Cavity and Systemic
      Disease.
AB  - Oral health is integral to general health. The oral cavity may harbor
      manifestations of systemic disease and can be the harbinger of early onset.
      Primary care providers (PCPs) can therefore use the oral cavity to support
      working diagnoses. Conversely, systemic diseases and treatments can affect oral
      health and require interactions between PCPs and dental providers. Acute oral
      manifestations of systemic disease may involve teeth and/or gums. This article
      reviews oral and systemic disease connections for some diseases, identifies
      issues that benefit patients through medical-dental collaboration, and highlights
      some nondental oral injuries that might confront PCPs or emergency medical
      providers.

PMID- 30213347
TI  - Benign and Malignant Oral Lesions in Children and Adolescents: An Organized
      Approach to Diagnosis and Management.
AB  - Oral lesions in children encompass a wide range of etiologies, including
      idiopathic entities as well as those related to an underlying systemic illness.
      In addition, oral masses include benign entities harboring locally destructive
      behavior and even malignancies in rare cases. Thorough patient history and
      detailed and efficient physical examination are critical for determining which
      lesions can be closely observed versus those require further diagnostic work-up.
      Understanding normal oral cavity anatomy is crucial for performing appropriate
      evaluation. This review describes the appropriate diagnostic and therapeutic
      strategies for oral cavity lesions and reviews the broad differential diagnosis
      of oral cavity masses.

PMID- 30213348
TI  - Periodontal Diseases and Traumatic Dental Injuries in the Pediatric Population.
AB  - This article provides an overview of periodontal diseases and traumatic dental
      injuries (TDIs) in children and adolescents, which are serious public health
      problems worldwide. Periodontal diseases, including gingivitis and periodontitis,
      commonly affect the oral soft tissues and teeth and often co-occur with other
      chronic diseases. TDIs are prevalent from an early age and carry high treatment
      costs. Behavioral and environmental factors contribute to both TDIs and
      periodontal diseases, but their etiology varies according to population
      characteristics and case definition. Both conditions may lead to pain, function
      impairment, esthetic problems, and psychosocial effects, with major consequences
      on quality of life.

PMID- 30213349
TI  - Preventing Oral Disease: Alternative Providers and Places to Address This
      Commonplace Condition.
AB  - Oral health disease in young children has not decreased, despite adequate
      modalities for treatment and prevention. Because many children may not see a
      dentist before oral disease has begun, disease progression can be expected,
      affecting short-term and long-term oral health. However, most children are seen
      by other health professionals frequently in their youngest years, providing a
      unique opportunity to help weave a safety net of oral health care until they are
      established in a dental home. This article details ways primary care providers
      can promote oral health, including ways to integrate ancillary dental
      professionals into the primary care home.

PMID- 30213350
TI  - Oral-Health-Related Quality of Life in Children and Adolescents.
AB  - This article describes child oral health-related quality of life measures and
      provides some examples of their use in determining the effect of clinical
      interventions, such as dental treatment under general anesthesia, orthodontic
      treatment, and treatment of orofacial clefting.

PMID- 30213351
TI  - Pediatric Oral Health Policy: Its Genesis, Domains, and Impacts.
AB  - Over recent years, pediatric oral health has become well established in the
      United States as an essential component of pediatric health policy as evidenced
      by the programs authorized and funded by Congress. These actions have improved
      access and utilization of dental care, engaged primary care pediatrics in oral
      health, and improved children's oral health outcomes. Nonetheless, there remains
      a host of authorized but unfunded approaches to addressing children's oral health
      through coverage, workforce, safety net, prevention, and surveillance. Child
      health advocates and practitioners need to actively engage as advocates if
      further improvements are to be attained through policymaking.

PMID- 30213352
TI  - A Developmental Approach to Pediatric Oral Health.
AB  - Orofacial growth and development is a complex process spanning the life course.
      This article provides an oral health overview in the context of overall growth,
      physical and social development from infancy through adolescence. It reviews oral
      health-specific developmental milestones during childhood (0-12 years) and
      adolescence (>=13 years). It examines issues particular to each age category or
      spanning multiple ages (eg, pediatric overweight and obesity, tobacco use, and
      dental trauma) in relation to oral health and development. In addition, the oral
      microbiome and its potential role in informing personalized oral health care
      across the life course is discussed.

PMID- 30213353
TI  - Infant Oral Health.
AB  - It may be easy to discount oral health in infancy because most infants are not
      born with teeth and only a few teeth erupt during the first year of life.
      Infancy, however, is a critical time for formation of habits. Positive habits,
      such as twice-daily brushing with fluoride toothpaste starting at first teeth
      eruption, provides topical fluoride, which is important for remineralization of
      the tooth and helps establish a lifelong healthy practice. Negative habits, such
      as bottle propping and frequent juice consumption, reinforce behaviors that
      promote caries and obesity. This article reviews normal dental development and
      eruption. Congenital anomalies affecting the mouth as well as acquired
      conditions, primarily dental caries, are reviewed. Oral health preventive
      modalities, including professionally applied products and home-based strategies,
      are discussed.

PMID- 30213354
TI  - The Role of Fluoride in the Prevention of Tooth Decay.
AB  - Although there are recommendations to prevent tooth decay by other means, this
      nonsystematic review finds that fluoride is the key to prevention and control of
      tooth decay. There are multiple fluoride modalities with effectiveness and safety
      of fluoride depending on dose and concentration. Prevention of tooth decay occurs
      at the individual level by fluoride use at home and with professional application
      and at the community level through fluoridation of water or salt.

PMID- 30213355
TI  - Early Childhood Caries.
AB  - Early childhood caries (ECC) is a common childhood disease with highest
      prevalence found in poor, socially disadvantaged, and minority groups. The main
      risk factors for ECC are frequent sugar consumption, lack of tooth brushing, and
      enamel hypoplasia. Contributory factors include environmental and psychosocial
      stresses that modify caregiver behaviors. Strategies for prevention include
      preventing mutans streptococci transmission, restricting dietary sugars, tooth
      brushing, topical fluoride applications, and early dental examinations. This
      article provides an overview of ECC based on current understanding of its cause,
      prevention, and management.

PMID- 30213356
TI  - The Burden and Management of Dental Caries in Older Children.
AB  - Dental caries is endemic in children and adolescents and has significant
      morbidity. This complex and chronic disease has both genetic and environmental
      etiologic factors. In children the preponderance of caries affects tooth surfaces
      with pits and fissures despite these representing only a small portion of the
      tooth surfaces that are at risk. Pit and fissure sealants are effective in
      preventing and managing noncavitated caries lesions in these surfaces. A variety
      of materials are clinically effective, and health care guidelines recommend the
      use of pit and fissure sealants as part of a comprehensive dental caries
      prevention program.

PMID- 30213357
TI  - Oral Health Disparities in Children: A Canary in the Coalmine?
AB  - Despite being largely preventable, oral diseases are still a major public health
      problem in child populations in many parts of the world. Increasingly, however,
      oral diseases disproportionately affect socially disadvantaged groups in society.
      It is unjust and unfair that children and families from disadvantaged backgrounds
      experience high levels of oral diseases. This article analyzes oral diseases
      through a health disparities lens. Action to combat oral health disparities
      requires a radical multifaceted strategy that addresses the shared underlying
      root causes of oral diseases, the social determinants of health inequality.

PMID- 30213358
TI  - Oral Health for US Children with Special Health Care Needs.
AB  - Children with special health care needs (CSHCN) are a vulnerable population
      subgroup, but little is known about their oral health, particularly regarding the
      prevalence and cause of tooth decay. This lack of knowledge is a barrier to
      progress in terms of developing evidence-based clinical interventions and
      policies aimed at promoting oral health in CSHCN. This article reviews the oral
      health literature pertaining to CSHCN, identifies critical knowledge gaps,
      highlights future research opportunities, and extends clinical recommendations to
      pediatric health care providers.

PMID- 30213359
TI  - Orthodontics in Children and Impact of Malocclusion on Adolescents' Quality of
      Life.
AB  - Orthodontics is the dental specialty concerned with the position of teeth and the
      relationship between the maxilla and mandible. Much evidence regarding the
      characteristics of normal occlusion during childhood/adolescence, the timely
      referral of children/adolescents to orthodontic treatment, and the impact of
      orthodontic outcomes on individuals' physical, functioning, and psychosocial well
      being exists in the literature. This body of evidence may be helpful for
      pediatricians and primary care physicians. For those willing to be skilled
      providers of health care to children/adolescents, knowledge of basic concepts of
      oral health may contribute to the communication among physicians, the young
      individual and their parents/caregivers.

PMID- 30213360
TI  - Teeth: Vital to Our Children's Health.

PMID- 30213361
TI  - Oral Health: A Critical Piece to Develop into a Healthy Adult.

PMID- 30213362
TI  - Insights into the art of recreation.

PMID- 30213363
TI  - Psychometric validation of the adapted Traditional Chinese version of the
      Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ).
AB  - BACKGROUND: Low back pain is a common health problem encountered by various
      populations among different countries. This prospective study aimed to translate
      and cross-culturally adapt the Japanese Orthopaedic Association Back Pain
      Evaluation Questionnaire (JOABPEQ) into Traditional Chinese and to assess its
      validity, reliability and sensitivity in Chinese patients experiencing low back
      pain. METHODS: Double forward and single back translation of the JOABPEQ was
      performed with cross-cultural adaptation. By convenience sampling, the final
      version of the translated JOABPEQ was administered to Chinese patients attending
      a specialty outpatient clinic with a history of back pain, followed by the
      traditional Chinese versions of Oswestry Disability Index (ODI) and Short Form-12
      version 2 (SF-12v2). Construct validity of the domains were assessed using
      Spearman's correlation test. Internal consistency was assessed by Cronbach's
      alpha (alpha). Sensitivity of the adapted JOABPEQ was determined by known group
      comparisons. RESULTS: A total of 100 patients were recruited. The translated
      JOABPEQ demonstrated excellent overall internal consistency (alpha: 0.912); and
      good internal consistency for the domains of Lumbar Function, Walking Ability,
      Social Life Function and Mental Health (alpha: 0.811, 0.808, 0.788, and 0.827
      respectively). Scores of all domains of the translated JOABPEQ had significant
      correlations (p < 0.01) with ODI at all domains, as well as with almost all
      domains of SF-12v2 (p < 0.01-0.05). The translated JOABPEQ was sensitive in
      detecting differences in patients with/without a history of previous spine
      surgery, and also between patients with acute/acute on chronic versus chronic
      pain in specific domains. CONCLUSIONS: The Traditional Chinese version of JOABPEQ
      has satisfactory psychometric properties in general, including adequate clinical
      and construct validity, and internal consistency in assessing Southern-Chinese
      patients with low back pain. It is demonstrated as a sensitive outcome measure.
      The translated JOABPEQ is verified for its use in the local clinical setting for
      patient assessment and future research.

PMID- 30213364
TI  - Is there a difference in clinical outcomes and repair integrity between
      arthroscopic single-row versus transosseous (anchorless) fixation? A
      retrospective comparative study.
AB  - BACKGROUND: Few studies have investigated clinical and structural outcomes after
      transosseous (TO) repair. The purpose of this study was to compare structural and
      clinical outcomes of rotator cuff tear, repaired arthroscopically, with a single
      row (SR) or transossoeus (TO) anchorless technique. METHODS: 96 patients who
      underwent an arthroscopic repair for superior or posterosuperior rotator cuff
      tear using TO (n:54) or a SR (n:42) were retrospectively enrolled in this study
      after evaluation of clinical and surgical notes. Functional evaluation was
      performed with the adjusted Constant score, and American Shoulder and Elbow
      Surgeons (ASES) score. Postoperative cuff integrity was determined through MRI
      study. RESULTS: Patients were recalled after a minimum follow-up of two years.
      All the patients were available for the study. In the SR group the Constant
      rating system showed a significant improvement from a preoperative average rating
      of 44.8 to an average of 85.7. In the group of TO repair the Constant rating
      system showed a significant improvement from a preoperative average of 46.1 to an
      average of 87.6 postoperatively. According to ASES index scores, the average
      total score improved from 42.8 to 92.0 in the anchor group and from 40.4 to 94.6
      in the TO group. There was no statistical difference between the two groups about
      clinical outcomes. Postoperative MRI revealed no differences in term of complete
      re-tears between the two techniques. In the SR group at MRI we observe
      significant more cases of rotator cuff with a Sugaya type III healing.
      CONCLUSIONS: Arthroscopic rotator cuff repair yielded successful clinical
      outcomes using SR and TO technique. However using the TO technique we saw less
      type 3 Sugaya readings on MRI suggesting a possible benefit with TO repair. LEVEL
      OF EVIDENCE II: Retrospective study.

PMID- 30213365
TI  - The effect of morphine added to periarticular multimodal drug injection or spinal
      anesthesia on pain management and functional recovery after total knee
      arthroplasty.
AB  - BACKGROUND: The efficacy of morphine added to periarticular multimodal drug
      injection (PMDI) for pain management after total knee arthroplasty (TKA) is
      controversial. Adding morphine to spinal anesthesia has reportedly improved pain
      relief for the first 24 h. We examined the effect of morphine added to PMDI or
      spinal anesthesia on pain management and functional recovery after TKA. METHODS:
      A total of 97 patients were randomized into three groups: in Group A (34
      patients), 10 mg morphine was added to PMDI; Group B (31 patients), 0.1 mg
      morphine was added to spinal anesthesia; and Group C (32 patients), morphine was
      added to neither the PMDI nor spinal anesthetic. To evaluate the efficacy of
      added morphine for pain management, we assessed rest pain, the number of times
      analgesics were used, and the time period until the first analgesic use. The
      adverse effects of morphine were assessed by counting the numbers of times
      vomiting occurred and antiemetics were used. Functional recovery was evaluated by
      recording the range of motion of the knee and the date of ability to walk.
      RESULTS: Rest pain was the least in Group B at 6 and 12 h after operation. The
      number of times analgesics were used was the least in Group B. The time period
      until the first analgesic use was the longest in Group B. The number of vomiting
      episodes was the least in Group C. The number of times antiemetics were used was
      higher in Group A than in Group C. There were no significant differences in the
      range of motion and date of ability to walk among the three groups. CONCLUSIONS:
      The efficacy of morphine added to PMDI was limited, and that of morphine added to
      spinal anesthesia disappeared within 20 h postoperatively. Adding morphine to
      PMDI or spinal anesthesia did not improve functional recovery and caused some
      adverse effects.

PMID- 30213366
TI  - Screening program including the Loco-check and fracture risk assessment tool
      (FRAX(r)) questionnaires for assessing locomotive syndrome in a municipality in
      Japan: A pilot study.
AB  - BACKGROUND: Although the concept of locomotive syndrome and its relevant test
      methods have been established, approaches for incorporating them into regular
      health checkups have not been established. We aimed to assess the utility and
      problems of including Loco-check and the fracture risk assessment tool (FRAX(r))
      as primary screening for locomotive syndrome during health checkups under the Act
      on Assurance of Medical Care for Elderly People (specified health checkup) in the
      municipality. METHODS: Loco-check and FRAX(r) questionnaires were mailed to
      subjects eligible for the 2015 specified health checkup in Asahi-machi, Japan.
      Subjects with more than one affirmative response in the Loco-check questionnaire
      (Loco-check positive) or whose FRAX(r) major osteoporotic fracture risk was >=10%
      (FRAX(r) positive) were identified as high risk and were evaluated in secondary
      checkups that included an locomotive syndrome risk test and sarcopenia and bone
      mineral density screenings. The degree of locomotive syndrome was assessed
      according to clinical diagnostic criteria of the Japanese Orthopaedic
      Association. RESULTS: Questionnaires were collected from 2209 subjects and
      included 1193 Loco-check-positive and 1108 FRAX(r)-positive subjects. There were
      367 FRAX(r)-positive subjects who were Loco-check-negative and 452 Loco-check
      positive subjects who were FRAX(r)-negative. Three hundred fifty-one subjects
      completed secondary checkups (42 in the no locomotive syndrome group, 171 in the
      locomo stage 1 group, and 138 in the locomo stage 2 group). Fourteen subjects had
      sarcopenia. CONCLUSION: The locomotive syndrome prevalence is high among subjects
      eligible for specified health checkups; these subjects were appropriate for
      locomotive syndrome screening. Using Loco-check and FRAX(r) in primary screening,
      many subjects can be evaluated for locomotive syndrome in a timely and cost
      effective manner, a more diversified risk of fall/fracture can be obtained, and
      the sensitivity of screening may be increased. These checkup protocols will
      assist in promoting locomotive syndrome checkups in municipalities throughout
      Japan.

PMID- 30213367
TI  - Feline Injection Site Sarcomas: Data from Switzerland 2009-2014.
AB  - Feline injection site sarcomas (FISS) were first described in the early 1990s.
      Despite extensive research, the pathogenesis of these tumours has not been
      elucidated conclusively. Their appearance and the marked increase in their
      incidence has been mainly connected to the injection of vaccines, and it is
      assumed that a chronic inflammatory reaction at the injection site triggers
      subsequent malignant transformation. The role of alum-based adjuvants has been
      discussed, but is controversial. The present study of the Swiss Feline Cancer
      Registry (SFCR) with data from 2009 to 2014 revealed a marked decrease of the
      incidence of fibrosarcomas compared with the previous observation period.
      Notably, this drop occurred after a non-adjuvanted feline leukaemia virus vaccine
      was introduced in Switzerland in 2007. This observation, together with the
      previous findings of the SFCR, further supports the notion that alum-adjuvanted
      vaccines are involved in the genesis of FISS and that non-adjuvanted vaccines
      might be safer for cats.

PMID- 30213368
TI  - Oral and Dental Examination Findings in Beech Martens (Martes foina).
AB  - Detailed clinical and radiographical descriptions of oral/dental pathology in the
      beech marten (Martes foina) are lacking. In the present study, skulls of M. foina
      from a museum collection (n = 109) were examined macroscopically according to
      predefined criteria and full-mouth dental radiographs were obtained. Occlusion
      was diagnosed as 'scissor bite' in 22.5% of evaluated skulls, 77% of evaluated
      skulls showed 'level bite' of incisors and 9.2% of evaluated skulls had 'open
      bites'. In three skulls, class III malocclusion was diagnosed. Linguoversion of
      the mandibular second incisor teeth was noted in all skulls. Of the maximum
      possible number of teeth (i.e. full set of teeth in each skull), 90.4% were
      available for examination, 6.4% were missing artifactually, 2.0% were absent
      presumably congenitally and in 1.2 % the absence was presumably acquired. In
      three skulls supernumerary teeth were noted, all being incisor teeth. In four
      skulls, unerupted maxillary canine teeth were noted and in one skull
      odontodysplasia of the maxillary canine teeth was diagnosed. All other teeth were
      considered normal in morphology. The number of roots per tooth varied in the
      mandibular second premolar, maxillary first molar and mandibular second molar
      teeth. The most common dental pathology was attrition/abrasion with 72 skulls
      (66%) and 857 teeth (24.1% of evaluated teeth) affected, followed by periodontal
      disease affecting 52 (47.7%) of skulls and 773 teeth (18.9% of evaluated teeth).
      Dental fractures were present in 49 (45%) skulls and 148 teeth (3.8% of evaluated
      teeth). Radiographically evident periapical lesions were detected in 11 (10.1%)
      skulls and 18 teeth (0.5% of evaluated teeth). Other rare abnormal findings
      included tooth resorption, enamel hypoplasia/hypocalcification, fenestrations at
      palatal root of maxillary first molar tooth and different bony changes.

PMID- 30213369
TI  - Computerized Cytomorphometric and Cytomorphological Analysis of Canine
      Transmissible Venereal Tumours.
AB  - Canine transmissible venereal tumour (CTVT) has three cytomorphological types:
      plasmacytic, lymphocytic and mixed type. Cytomorphometry, a method of
      computerized image analysis, has been used recently in veterinary medicine. This
      study compared the nuclear and cellular morphometric parameters (i.e. radius,
      diameter, perimeter and area) in different types of CTVT with other canine round
      cell tumours including lymphoma, mast cell tumour (MCT) and histiocytic tumour
      (HCT). We also evaluated the relationship between clinical information and the
      different CTVT cytomorphologic types. CTVT cells from 44 dogs revealed that the
      measured parameters were significantly different between different round cell
      tumours and among the CTVT cytomorphological types. CTVT had the largest cells,
      followed by HCTs, MCTs and lymphomas. The mixed type of CTVT had the largest
      nuclear and cellular size, followed by the plasmacytic and lymphocytic types.
      Lymphocytic CTVTs had less aggressive biological behaviour than the other types.
      Mixed type CTVTs were more likely to show malignant behaviour including
      metastasis and resistance to chemotherapy; however, there was no significant
      correlation between cytomorphological type of CTVT and response to chemotherapy.

PMID- 30213370
TI  - Complex Gill Disease: an Emerging Syndrome in Farmed Atlantic Salmon (Salmo salar
      L.).
AB  - Gill disorders have become a significant problem during the marine phase of
      farming Atlantic salmon (Salmo salar L.). The term complex gill disease (CGD)
      includes a wide range of clinical gill disease presentations generally occurring
      from the end of summer to early winter on marine Atlantic salmon farms. The gross
      and histological lesions observed are the resultant culmination of exposure to a
      mixture of environmental insults, pathogenic organisms and farm management
      practices. None of the three principal agents purportedly associated with CGD
      (Desmozoon lepeophtherii, salmon gill poxvirus or Candidatus Branchiomonas
      cysticola) have been cultured successfully in-vitro, so individual in-vivo
      challenge studies to identify their pathogenesis have not been possible. Studies
      of cohabitation of single pathogen-infected fish with naive fish, and
      epidemiological investigations are required urgently to elucidate the roles of
      these pathogens and other factors in CGD.

PMID- 30213371
TI  - Ganglioneuromatosis of the Gallbladder in a Dog with Cholecystitis and
      Cholestasis.
AB  - A 2-year-old entire female mixed-breed dog was presented with signs of
      cholestasis. Abdominal ultrasonography revealed a gallbladder with a thickened
      and hyperechoic wall and luminal calculi. Exploratory laparotomy with
      cholecystectomy was performed and histopathological examination of the specimens
      from the cholecystectomy demonstrated extensive proliferation of large, prominent
      nerves containing ganglion cells with no atypia mainly located in the gallbladder
      mucosa. The neural nature of these components was confirmed by
      immunohistochemical labelling with antibodies specific for synaptophysin, glial
      fibrillary acidic protein, S100 protein and neurofilaments. Based on these
      findings, the lesion was diagnosed as ganglioneuromatosis. Reports of
      ganglioneuromatosis in animals have so far been restricted to the intestine. This
      is the first case of ganglioneuromatosis affecting the gallbladder in an animal
      in which no intestinal involvement was apparent.

PMID- 30213372
TI  - Sympathetic Innervation and Adrenergic Receptors in Equine Deep Digital Flexor
      Tendinopathy: Preliminary Results.
AB  - The aim of this study was to delineate the pattern of sympathetic innervation in
      the suprasesamoidean region of the deep digital flexor tendon (DDFT) in horses
      with tendinopathy by immunohistochemical labelling for tyrosine hydroxylase (TH)
      and alpha-1 adrenergic receptor (alpha1-AR). Twelve forelimbs were obtained from
      10 horses with DDFT tendinopathy and six feet obtained from six horses were used
      as healthy controls. Post-mortem radiographic, ultrasonographic and gross
      examinations were performed on the suprasesamoidean area of the DDFT to assess
      the presence of tendinopathy. Longitudinal sections were collected and processed.
      Lesions were classified as core lesions, dorsal border lesions and parasagittal
      oblique splits. Immunohistochemistry was performed and the degree of
      immunoreaction was classified as absent, mild or marked. Seven core lesions, four
      dorsal border lesions and one parasagittal oblique split were identified. There
      was no increased expression of sympathetic innervation in samples with a dorsal
      border lesion of the DDFT compared with healthy samples. In contrast, core
      lesions showed increased expression of alpha1-AR and reduced expression of TH,
      which supports the hypothesis of a compensatory imbalance between the sympathetic
      mediator and the sympathetic receptors as a cause or effect of structural damage.
      In addition, adrenergic activation could stimulate cell proliferation and
      differentiation within these lesions.

PMID- 30213374
TI  - The Journal of Comparative Pathology Educational Trust and Petplan Charitable
      Trust Joint Research Award in Veterinary Pathology.

PMID- 30213373
TI  - Metaphyeal and Diaphyseal Dysplasia of the Third Cervical Vertebra Secondary to
      Physeal Necrosis in a Quarter Horse Foal.
AB  - Ischaemia-induced physeal injury has not been described previously in the horse.
      A 1-month-old Quarter horse foal was submitted for necropsy examination due to an
      acute onset of ataxia followed by a 4-week history of progressive decline. Focal
      narrowing of the spinal canal due to ventral compression by the rotation of the
      cranial aspect of the third cervical vertebra (C3) was observed. The metaphysis
      and diaphysis of C3 were markedly shortened and white-tan in colour.
      Microscopically, there was complete loss of the dorsal compact bone of C3 and
      replacement of 80% of the physis that runs parallel to the vertebral canal with
      fibrous tissue and thickened viable trabecular bone. Both cranial and caudal
      physes of C3 showed widespread bands of coagulative necrosis of the hypertrophic
      and calcifying zones. Marked bone marrow hypoplasia with slight fibrosis was
      observed in the metaphyses and diaphysis. There was no evidence of fracture or
      inflammation. The epiphyses were microscopically unremarkable. It was
      hypothesized that a regional transient incomplete and possibly multiphasic
      ischaemia involving the nutrient artery caused necrosis of the physes, resulting
      in dysplasia of the bone. Ischaemic injury to the physis should be considered in
      the pathogenesis of focal bone dysplasia in horses.

PMID- 30213375
TI  - Expression of Stem Cell Factor in Feline Mast Cell Tumour.
AB  - Stem cell factor (SCF) is a ligand of the molecule Kit, which is expressed in
      mast cells and is important for mast cell proliferation, migration and survival.
      Mast cell tumours (MCTs) are associated with mutations of c-kit, a proto-oncogene
      encoding the Kit protein. In this study, we examined SCF expression in 23 samples
      of feline MCTs. SCF expression was detected in 10 cutaneous MCTs and a case of
      splenic mastocytosis. In the cutaneous MCTs, SCF-positive tumour cells were
      located at the margins. Kit was expressed in eight of the 10 cutaneous cases of
      SCF-expressing MCTs. In these cases, Kit-positive cells were located near to SCF
      positive cells, and SCF/Kit double-positive tumour cells were found. Ki67
      positive tumour cells were not found near to SCF-positive cells. These results
      suggest that SCF autocrine/paracrine mechanisms are involved in the expansion of
      cutaneous MCTs, but not in tumour proliferation.

PMID- 30213376
TI  - Corrigendum to "Symptom severity prediction from neuropsychiatric clinical
      records: Overview of 2016 CEGS N-GRID shared tasks Track 2" [J Biomed Inform.
      2017 Nov;75S:S62-S70].

PMID- 30213377
TI  - Quantitative non-invasive imaging of target engagement in small animals.

PMID- 30213379
TI  - Safety and Accuracy of Anatomic and Lateral Fluoroscopic-Guided Placement of C2
      Pars/Pedicle Screws and C1 Lateral Mass Screws, and Freehand Placement of C2
      Laminar Screws.
AB  - OBJECTIVE: To evaluate the safety and accuracy of anatomic- and lateral
      fluoroscopic-guided placement of C2 pars/pedicle, C1 lateral mass screws, and
      freehand placement of C2 laminar screws. METHODS: All the patients who underwent
      posterior cervical/occipitocervical fixation that involved the placement of C1/C2
      screws during a 5-year period (2011-2015) at our institute were included in this
      study. RESULTS: C1/C2 screws were placed in a total of 94 patients during this
      period. A total of 97 C1 lateral mass, 49 C2 pars, 24 C2 pedicle, and 82 C2
      laminar screws were placed in these patients. C1 lateral mass screws and C2
      pars/pedicle screws were placed under anatomic and lateral fluoroscopic guidance.
      C2 laminar screws were placed by a freehand technique. The mean length (range) of
      various C2 screws was 16.4 +/- 2.6 mm (12-22 mm) for pars screws, 18.8 +/- 2.7 mm
      (14-24 mm) for pedicle screws, and 25.6 +/- 3.4 mm (18-32 mm) for laminar screws.
      Postoperative CT imaging done in all patients before discharge revealed
      malposition of 2 laminar screws with breach of the inner cortex. The position of
      the remaining C1/C2 screws was perfect. The superior and medial angulation of the
      pars screws and superior angulation of the pedicle screws as measured in
      postoperative CT images were found to significantly deviate from the angles
      described in the literature. There was no mortality, vertebral artery injury, or
      neurologic injury related to C1/C2 screw placement in this series. CONCLUSIONS:
      Anatomic and lateral fluoroscopic-guided placement of C2 pars/pedicle screws and
      C1 lateral mass screws and freehand placement of C2 laminar screws is extremely
      safe.

PMID- 30213381
TI  - Usefulness of Pulsed Dye Laser in Cutaneous Lupus Erythematosus.

PMID- 30213380
TI  - Commentary: Dimensions of the maxillary sinus drainage system associated with
      pathology of the sinus.

PMID- 30213382
TI  - Implementation of an adhesive small bowel obstruction protocol using low-osmolar
      water soluble contrast and the impact on patient outcomes.
AB  - BACKGROUND: Small bowel obstruction (SBO) is a common condition leading to
      numerous hospital admissions and operations. Standardized care of adhesive SBO
      patients has not been widely implemented in hospital systems. METHODS: A
      prospective cohort of SBO patients was compared to a historical cohort of SBO
      patients after implementation of a SBO protocol using evidence-based guidelines
      and Omnipaque, a low-osmolar water soluble contrast. Patients without a history
      of abdominal surgery were excluded and data was collected through chart review.
      RESULTS: Univariate analyses demonstrated a decrease in both LOS by 1.35 days and
      in the proportion of patients receiving surgery (37% vs 25%; p < 0.05). There was
      a decrease in time to surgery, rate of SBR, and rate of complications, yet an
      increase in readmission, although these findings were not statistically
      significant. CONCLUSIONS: Utilizing an evidence-based SBO protocol can lead to
      shorter LOS and may result in fewer operations for adhesive SBO patients.

PMID- 30213383
TI  - Effect of Guideline-Based Therapy on Left Ventricular Systolic Function Recovery
      After ST-Segment Elevation Myocardial Infarction.
AB  - Little is known about the proportion of ST-segment elevation myocardial
      infarction (STEMI) patients treated with primary percutaneous coronary
      intervention, who have reduced left ventricular ejection fraction (LVEF) within
      48 hours (baseline) of admission and exhibit LVEF recovery under optimal
      guideline-based medical treatment. Therefore, the present study evaluates the
      evolution of LVEF in patients after STEMI and under guideline-based medical
      therapy. In 2,853 STEMI patients treated with primary percutaneous coronary
      intervention, echocardiography was performed at baseline and at 6 months follow
      up. Patients with previous myocardial infarction, reinfarction, coronary artery
      bypass grafting or incomplete echocardiographic data at 6 months follow-up were
      excluded. Reduced LVEF at baseline was defined as <40%. LVEF recovery was defined
      as LVEF >50% at 6 months follow-up. The prevalence of LVEF <40% at baseline was
      13% (n = 371 patients; mean age 60 [range 33 to 88] years; 76% men). At follow
      up, 31% of patients remained with a LVEF <40%, 30% showed a LVEF between 41% and
      49% and in 39% of patients LVEF improved to >50%. There were no differences in
      usage of guideline-based medications at discharge across groups. On multivariable
      analysis, peak troponin T levels (odds ratio [OR] 0.895; p < 0.001), baseline
      LVEF (OR 1.069; p = 0.023) and absence of significant mitral regurgitation (OR
      0.376; p = 0.018) were independently associated with LV recovery at follow-up. In
      conclusion, the prevalence of LVEF <40% is low. With optimal medical therapy,
      LVEF normalizes in 39% of patients. Smaller enzymatic infarct size, baseline LVEF
      and absence of mitral regurgitation were independently associated with LVEF
      recovery at follow-up.

PMID- 30213385
TI  - Re: Letter to the Editor of Public Health in response to 'Increasing inequality
      in childhood obesity in primary schools in a northern English town'.

PMID- 30213384
TI  - Characteristics and Outcomes of Patients Hospitalized With Suspected Acute
      Coronary Syndrome in Whom the Diagnosis is not Confirmed.
AB  - Patients admitted with suspected acute coronary syndrome (ACS) in whom the
      diagnosis is not confirmed are poorly characterized. In a contemporary registry
      of consecutive patients hospitalized with suspected ACS as the primary diagnosis,
      we assessed characteristics on admission and in-hospital and 6-month mortality of
      patients discharged with other diagnoses and compared this subgroup with true ACS
      patients. Of 2557 patients included, 9.0% were discharged with a non-ACS
      diagnosis such as nonspecific chest pain, myopericarditis, stress cardiomyopathy,
      hemodynamic disturbances, heart failure, myocardial, pulmonary or valvular
      disease, or others. Compared with true ACS patients, those with other diagnoses
      were younger, more often female, and had less cardiovascular risk factors. Both
      groups had comparable rates of nonchest pain presentation and similar hemodynamic
      characteristics on admission. Non-ACS patients presented less often with Q waves
      or with ST-segment or T-wave changes and had a lower Global Registry of Acute
      Coronary Events score than true ACS patients. In-hospital (4.3 vs 4.0%,
      respectively, p = 0.834) and 6-month (5.4 vs 8.0%, respectively, p = 0.163)
      mortality rates were comparable in both groups. However, if patients in the non
      ACS group were divided into subgroups with nonspecific chest pain (6.2% of total)
      or other diagnoses (2.8% of total), major differences in in-hospital (0.0 vs
      13.9%, respectively, p < 0.001) and 6-month (0.7 vs 15.7%, respectively, p <
      0.001) mortality rates would become apparent and remain after multivariable
      adjustment. In conclusion, in a non-negligible proportion of patients
      hospitalized with suspected ACS, this diagnosis is not confirmed. Prognosis of
      these patients follows a bimodal pattern, being excellent in those with
      nonspecific chest pain but worse than that of true ACS patients in the rest.
      Efforts are necessary to ensure prompt identification and early risk
      stratification of these patients allowing appropriate management decisions.

PMID- 30213386
TI  - Should UK based Physiotherapists Choose Wisely?
AB  - In 2012 the Choose Wisely campaign was launched in the United States in order to
      address concerns regarding medicalisation, over diagnosis and medical
      consumerism. The campaign has now spread internationally and includes a number of
      countries including Canada, Australia, New Zealand and Germany. The primary aim
      of the campaign is to facilitate healthcare professionals and patients to
      question the overall utility of medical interventions. Professionals through
      their professional organisations identify at least five commonly used
      interventions or tests, within their areas of speciality, which they feel
      provided no or little benefit to patients. This paper provides the background to
      the Choose Wisely campaign. The paper reviews the concepts of medicalisation,
      over diagnosis and medical consumerism, before considering the utility of the
      campaign in the UK alongside other forms of governance such as NICE. The paper
      goes on to consider distributive justice as the principal ethical issue related
      to the campaign. The paper concludes by asking if UK based Physiotherapists
      should Choose Wisely.

PMID- 30213387
TI  - Editor's introduction.

PMID- 30213388
TI  - Dissecting aggressive B-cell lymphoma through genomic analysis - What is
      clinically relevant?
AB  - The aggressive B-cell lymphomas are a diverse collection of cancers grouped
      together based on clinical behavior and derivation from B lymphocytes. Genomic
      analyses on these tumours are now translating into improved classification
      systems and identification of underpinning targetable biology. Simple karyotyping
      revealed key translocations involving MYC, BCL2, and BCL6 that have impacted
      lymphoma classification in the World Health Organization classification scheme.
      Subsequently, gene expression profiling identified molecular subgroups within the
      most common lymphoma, diffuse large B-cell lymphoma (DLBCL): activated B-cell
      like and germinal centre B-cell-like. Finally, next generation sequencing has
      revealed a modest number of frequently mutated genes and a long list of
      infrequent mutations. The mutational landscapes involve diverse genes associated
      with dysregulated signalling, epigenetic modification, blockade of cellular
      differentiation, and immune evasion. These mutational "signatures" are enriched
      in the different aggressive lymphoma subtypes impacting phenotypes and
      identifying therapeutic targets. Challenges to implementing genomic assays into
      clinical practice remain.

PMID- 30213389
TI  - Optimizing initial therapy in DLBCL.
AB  - Diffuse large B-cell lymphoma (DLBCL) is a group of lymphomas comprising
      heterogeneous molecular and biological subtypes, reflected in a broad range of
      clinical outcomes. With the standard R-CHOP regimen of cyclophosphamide,
      doxorubicin, vincristine, and prednisone plus rituximab administered every 21
      days, the treatment failure rate remains unacceptably high in certain DLBCL
      subsets. Here we review possible avenues for optimizing initial therapy. The role
      of functional imaging and biological features, such as double-hit lymphomas,
      defined by the dual translocation of MYC and BCL2, and dual protein-expresser
      lymphomas, defined by the overexpression of MYC and BCL2, activated B-cell (ABC)
      like DLBCL, to better define these high-risk patient subsets, and their use to
      guide and personalize treatment decisions are discussed. Secondly, the
      implications of varying dose-intensification of the various agents administered,
      and the link to imaging are reviewed. Thirdly, the results of the addition of
      novel drugs to standard R-CHOP will be analyzed, when added at induction or in
      maintenance. Finally, with CNS relapse in DLBCL representing a major and
      devastating unmet medical need, an overview and future directions for CNS
      prophylaxis is presented.

PMID- 30213390
TI  - Management of relapsed/refractory DLBCL.
AB  - Diffuse large B cell lymphoma represents the most common type of non-Hodgkin
      lymphoma. Although the curability rate is high, around 40% of patients will
      relapse or exhibit refractory disease. To obtain long-term disease-free survival
      after relapse, an intensive salvage regimen followed by autologous steam cell
      transplant remains the standard of care. However, more than 60% of patients will
      be transplant ineligible, presenting a therapeutic challenge. In this setting,
      there is no definitive standard approach, as management should be individualized
      according to patient tolerance. Importantly, these transplant ineligible patients
      are ideal for consideration of novel agents. In this review, we will discuss the
      incidence, outcome, and management of relapsed and refractory DLBCL, as well as
      explore some of the novel agents in development.

PMID- 30213391
TI  - Successful role of radiation therapy: Account for every single gray and make
      every single gray count.
AB  - Combined-modality treatment involving immuno-chemotherapy with or without
      radiation has become the mainstay of treatment for aggressive lymphomas such as
      diffuse large B-cell lymphoma (DLBCL). Long-term goals in the treatment of DLBCL
      are to keep improving the therapeutic ratio and to extend survival; these goals
      have been accomplished largely by (a) gaining insight into disease biology and
      developing biologically based criteria to guide choice of therapy, (b) avoiding
      unnecessarily long courses of chemotherapy, and (c) reducing both the size of the
      radiation fields and the radiation dose. Here I review the available literature
      on which clinical presentations can benefit the most from radiation; how the
      availability of advanced imaging has led to radical changes in the use of
      radiation therapy in DLBCL; and examples of best-practice radiation planning and
      delivery.

PMID- 30213392
TI  - Double hit lymphoma: How do we define it and how do we treat it?
AB  - Double/triple hit lymphoma is recognised as a distinct entity within the
      heterogeneous group of high grade B-cell lymphomas, accounting for between 5 and
      10% of cases of diffuse large B-cell lymphoma. Under the WHO 2016 it is now known
      as high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6.
      When treated with standard chemotherapy it has a poor outcome. There is currently
      no standard of care for the management of this condition. Diagnosing double hit
      lymphoma requires identification of translocations of MYC and BCL2 and/or BCL6.
      This review will discuss the role of stratification to screen cases based on
      immunohistochemical profiling as a viable option. Treatment options in the
      frontline and relapsed setting will be reviewed based on the current literature.
      Recognition of the risk of CNS involvement and how best to manage this will be
      discussed. Future considerations and current research will be described.

PMID- 30213393
TI  - The unique biology and treatment of primary mediastinal B-cell lymphoma.
AB  - The unique biological features of primary mediastinal large B-cell lymphoma are
      offering suggestions for the development and application of innovative drugs in
      patients who do not respond to first-line regimens or relapse. This lymphoma, in
      fact, is characterised by high rates of curability with standard anthracycline
      containing chemoimmunotherapy regimens, but still displays a severe prognosis if
      adequate responses are not rapidly achieved or if the disease recurs.
      Radiotherapy has proved to be effective to consolidate responses after induction,
      but it may be safely avoided in certain cases, especially when a metabolic
      complete response is obtained, as to reduce the incidence of radiation-induced
      long-term sequelae. The current management of this lymphoma, both at diagnosis
      and at relapse, is reviewed in this paper, along with the description of its
      peculiar biological panorama.

PMID- 30213394
TI  - An update in treating transformed lymphoma.
AB  - Indolent lymphomas typically have a prolonged course and favorable prognosis.
      Recent data support survival times that can reach several decades, even if
      periodic treatment is needed to manage symptoms or stabilize disease. However,
      all indolent lymphomas have the potential to undergo transformation to an
      aggressive phenotype, clinically characterized by a rapid progression of
      adenopathy, new-onset constitutional symptoms, or laboratory abnormalities, and
      the immediate need for therapeutic intervention. The most common scenario is
      transformation of follicular lymphoma to either diffuse large B-cell lymphoma or
      high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations; however,
      other indolent subtypes such as marginal zone lymphoma, lymphoplasmacytic
      lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, or even
      nodular lymphocyte predominant Hodgkin lymphoma, can undergo similar histologic
      transformation. The prognosis of transformed lymphomas has historically been
      quite poor, but there is ample evidence this is changing in the rituximab era.
      This article will provide a review of transformed lymphomas with an emphasis on
      treatment and the nuances of diagnosis and clinical management. Unless otherwise
      specified, all discussion in this review pertains to transformed follicular
      lymphoma which is the more common scenario and the subtype with the most robust
      data. In many cases, this information can be extrapolated and applied to other
      indolent histologies (i.e. transformed marginal zone lymphoma); however, several
      other clinical scenarios, such as Richter's transformation and "double hit"
      transformations, warrant a distinct discussion and will be reviewed separately.

PMID- 30213395
TI  - Improving outcomes in primary CNS lymphoma.
AB  - Primary central nervous system lymphoma (PCNSL) is an aggressive disease with
      previously poor prognosis. The advent of high-dose methotrexate-based induction
      regimens as well as use of consolidation therapy has greatly improved this
      prognosis in recent decades, but durable remission still eludes half of patients.
      In this review, we summarize the progress made in the treatment of PCNSL as well
      as the challenges that remain, with a focus on defining optimal induction and
      consolidation regimens, including the promise of developing biotherapies. Future
      studies will help delineate the best combination of existing and novel treatment
      strategies, with the goal of expanding the cohort of patients achieving a cure.

PMID- 30213396
TI  - Evolving treatment strategies in mantle cell lymphoma.
AB  - Mantle cell lymphoma is an incurable, moderately aggressive B cell lymphoma.
      While a small proportion of patients with indolent disease can be managed
      expectantly, most patients require treatment. The therapeutic approach is driven
      by physician recommendation, patient choice, age, fitness and comorbidities.
      Young, fit patients often receive combination chemoimmunotherapy, including high
      dose cytarabine, with autologous stem cell transplant. Recent data has indicated
      benefit from maintenance rituximab following autologous stem cell transplant.
      Ongoing trials are investigating combinations of chemotherapy and targeted agents
      as well as the role of minimal residual disease guided therapy. Older, less fit
      patients often receive bendamustine and rituximab or anthracycline based
      regimens. Maintenance rituximab is typically administered in older MCL patients
      after anthracycline based chemotherapy although its use after bendamustine based
      therapy is not supported by current data. Current trials focus on refining this
      regimen with the addition of targeted agents. In the relapsed and refractory
      setting, novel agents have demonstrated activity although durability of responses
      remains unsatisfactory.

PMID- 30213397
TI  - Burkitt lymphoma- a rare but challenging lymphoma.
AB  - Burkitt lymphoma (BL) is a rare, aggressive subtype of non-Hodgkin lymphoma
      affecting approximately 1500 patients per year. Three forms of BL exist
      (sporadic, endemic, immunodeficiency associated) and the endemic form was first
      discovered as being driven by the Epstein Barr virus in areas of the world where
      malaria is prevalent. BL has the characteristic t8; 14 cytogenetic translocation
      that leads to constitutive activation of the MYC gene, which drives BL cell
      division. Therapy of BL has resulted in cure for many patients but significant
      toxicity and treatment related complications remains problematic in the approach
      to BL therapy. Treatment options for relapsed and refractory disease remain
      limited however novel treatments are being studied to block MYC activation, and
      cold lead to promising options for patients with relapsed and refractory disease.

PMID- 30213398
TI  - Monitoring clinical outcomes in aggressive B-cell lymphoma: From imaging studies
      to circulating tumor DNA.
AB  - Recent guidelines have de-emphasized the role of routine surveillance computed
      tomography (CT) scans for diffuse large B-cell lymphoma (DLBCL) patients who
      achieve a complete response to front-line therapy. This shift in practice
      recommendations was prompted by retrospective studies that failed to demonstrate
      clear clinical utility for surveillance CT in unselected DLBCL patients.
      Controversy remains, however, over the role of routine surveillance CT in the
      highest risk patients for treatment failure who would remain candidates for
      aggressive salvage therapies. Novel high-throughput sequencing methods can non
      invasively monitor tumor-specific DNA in the blood and offers clear advantages
      designed to overcome fundamental limitations of CT scans. This review will
      discuss the current controversies surrounding monitoring clinical outcomes in
      aggressive B-cell lymphomas, with a specific emphasis on DLBCL. Fundamental
      limitations of imaging scans will be addressed and the potential of monitoring
      circulating tumor DNA as an adjunct or replacement for CT scans will be
      discussed.

PMID- 30213399
TI  - The promise of CAR T-cell therapy in aggressive B-cell lymphoma.
AB  - Relapsed or refractory aggressive B-cell lymphoma has an extremely poor prognosis
      and efforts to develop novel therapies for these patients have failed for almost
      four decades until the advent of chimeric antigen receptor (CAR) T-cell therapy.
      Within the last one year, two anti-CD19 CAR T-cell therapy products, axicabtagene
      ciloleucel and tisagenlecleucel, were approved by the United States Food and Drug
      Administration for the treatment of relapsed or refractory large B-cell lymphoma
      after at least two lines of systemic therapy based on multicenter single-arm
      phase two clinical trials. Here, we will discuss the different components of the
      CAR construct and their mechanisms of action, the role of conditioning
      chemotherapy, the efficacy and toxicity observed with anti-CD19 CAR T-cell
      therapies in aggressive B-cell lymphomas, and emerging strategies to further
      improve the safety and efficacy of these highly promising approaches.

PMID- 30213400
TI  - Immunotherapy in aggressive B-cell lymphomas.
AB  - The idea that the immune system could be co-opted to treat cancer is not new; it
      has existed for centuries. However, what is new is the advancement of our
      understanding of how the immune system is regulated and how a tumor evolves to
      evade an immune response. This knowledge, combined with modern technologies to
      manipulate the immune system, both pharmacologically and genetically, has led to
      the realization of immuno-oncology as a new frontier in cancer therapeutics. This
      review will focus on pharmacologic immunotherapies in aggressive B cell
      lymphomas: checkpoint inhibition and bispecific antibodies. The success of
      checkpoint inhibitors in this heterogenous collection of diseases has largely
      been limited to those that genetic aberrations involving genes for checkpoint
      ligands, whereas bispecific antibodies appear to be more broadly efficacious but
      responses are short-lived. Investigation into the tumor microenvironment for each
      of the aggressive B cell lymphoma histologies, and interrogation of mechanisms of
      resistance as well as predictors of response to these immunotherapy approaches,
      will undoubtedly identify rational combinations as well as new therapeutic
      targets such that outcomes can be improved across these diseases.

PMID- 30213401
TI  - Peripheral T-cell lymphoma - are we making progress?
AB  - Peripheral T cell lymphoma (PTCL) is a rare subtype of non-Hodgkin lymphoma.
      PTCLs are heterogeneous in terms of biology, but generally have more aggressive
      features and poorer outcomes than aggressive B-cell lymphomas when treated with
      combination chemotherapy. While the best long-term results are still seen with
      intensive chemotherapeutic approaches, significant progress has been made with
      molecular profiling identifying genetic drivers of PTCL that could serve as
      therapeutic targets. Tailoring therapy to different subtypes of PTCL may lead to
      more individualized approaches with the hope of improved outcomes. In this paper,
      we review current therapies for treatment of PTCL, newly identified molecular
      markers, and the role of emerging therapy and novel combinations of existing
      agents.

PMID- 30213402
TI  - Extranodal NK/T-cell lymphoma: Updates in biology and management strategies.
AB  - Extranodal NK/T-cell lymphoma, nasal type (ENKL), is a rare lymphoma subtype of
      peripheral T/NK-cell lymphoma that is very common in East Asia and Latin America.
      Two-thirds of patients have localized disease in the nasal cavity or adjacent
      sites. Large retrospective studies have revealed the clinicopathologic features
      of ENKL patients, identified risk factors for short survival time, and developed
      prognostic models. Next-generation sequencing studies have provided a
      comprehensive list of recurrent mutations in ENKL. Since the early 2000s, disease
      specific therapeutic approaches have been developed, and the standard of care for
      ENKL has markedly changed. Non-anthracycline-containing chemotherapy with or
      without radiotherapy is the current standard approach for ENKL treatment.
      Emerging therapies, including the use of immune checkpoint inhibitors, are being
      investigated.

PMID- 30213403
TI  - Integrating novel systemic therapies for the treatment of mycosis fungoides and
      Sezary syndrome.
AB  - Novel systemic therapies are generally prescribed to patients with advanced-stage
      disease or those with early-stage disease refractory to skin-directed therapies.
      In general, systemic chemotherapy should be reserved for patients who fail to
      respond to biological agents. Such biological agents include interferon alfa,
      bexarotene, histone deacetylase inhibitors (vorinostat, romidepsin), brentuximab
      vedotin and mogamulizumab. Extracorporeal photopheresis is particularly effective
      for patients with Sezary Syndrome. Allogeneic transplantation is becoming
      increasing used for younger patients. Novel agents in advanced development
      include the monoclonal antibody IPH4102,duvelisib,and the new modified
      formulation of denileukin diftitox. The choice of agents for patients is
      typically a balance of patient factors (age, co-morbidities, geographic
      location), relative efficacy and toxicity.

PMID- 30213404
TI  - [Autologous microsurgical breast reconstruction by free perforator flap at the
      expense of the Profund Femoral Artery (PAP): Harvest technique, modeling and
      results].

PMID- 30213405
TI  - Implications of the Affordable Care Act on Surgery and Cancer Care.
AB  - The Patient Protection and Affordable Care Act increased health insurance
      coverage to millions in the United States, transformed both the private and
      public insurance markets, and invested in care delivery changes in an attempt to
      increase the quality and value of health care. How these changes have translated
      to improved long-term oncologic outcomes, including for survivorship, remains to
      be seen. Newer models of payment and care delivery attempt to improve both short
      term and long-term quality while better controlling cost trends. The extent to
      which cancer care delivery will be affected also needs further study and
      optimization.

PMID- 30213406
TI  - Repealing the Affordable Care Act and Implications for Cancer Care.
AB  - Calls to repeal the Affordable Care Act (ACA) have become increasingly frequent.
      Most attempts to repeal the ACA have targeted specific policies rather than the
      ACA as a whole. This article describes the specific policies under debate and the
      ramifications of repealing each of them. Specific attention is given to insurance
      coverage, individual premiums, and budgetary impact. Based on the literature
      regarding the ACA's impact to date, the impact of ACA repeal on Surgical oncology
      care is predicted.

PMID- 30213407
TI  - Quality Measurement and Pay for Performance.
AB  - Recent debate has focused on which quality measures are appropriate for surgical
      oncology and how they should be implemented and incentivized. Current quality
      measures focus primarily on process measures (use of adjuvant therapy, pathology
      reporting) and patient-centered outcomes (health-related quality of life). Pay
      for performance programs impacting surgical oncology patients focus primarily on
      preventing postoperative complications, but are not specific to cancer surgery.
      Future pay for performance programs in surgical oncology will likely focus on
      incentivizing high-quality, low-cost cancer care by evaluating process measures,
      patient-centered measures, and costs of care specific to cancer surgery.

PMID- 30213408
TI  - Surgical Collaboratives for Quality Improvement.
AB  - How best to improve the surgical quality remains unknown. Historically, most
      efforts were either top down national policy efforts or local hospital/practice
      level efforts. This article reviews the limitations of these methods and how
      collaborative quality improvement a mix of local, regional, and national efforts
      is the most effective means of achieving sustainable, meaningful improvement in
      surgical care.

PMID- 30213409
TI  - Utilizing Big Data in Cancer Care.
AB  - Clinical research has boomed over the past decade, with the development of
      multiple clinical datasets that are available for retrospective review. However,
      data remain incomplete based on fragmented reporting, provider change, and loss
      of follow-up. New technologies are being developed to assist with this
      limitation, by joining health care systems' medical records, and tracking
      Medicare claims files. The future of health care will rely more heavily on these
      systems, and artificial intelligence to quickly pull relevant clinical and
      genomic data regarding particular diagnoses, as a means to personalize medicine.
      This article reviews current advances in management of Big Data.

PMID- 30213410
TI  - Cancer Care Delivery Research: A Path to Improving the Quality of Oncologic
      Surgical Care.
AB  - The goal of cancer care delivery research (CCDR) is to inform sustainable
      practice changes that will provide better clinical outcomes and patient
      experience guided by patient values. CCDR encompasses salient concepts from other
      well-established research approaches and spans the continuum of research from
      hypothesis generation to effectiveness studies to policy development. CCDR
      incorporates pertinent attributes, such as saliency to stakeholders, inclusion of
      diverse participants, and implementation into real-world settings. This article
      provides examples of CCDR studies, focusing specifically on how CCDR can improve
      the quality of oncologic surgical care.

PMID- 30213411
TI  - Engaging Stakeholders and Patient Partners.
AB  - Recent advances in engagement of stakeholders and patient partners in clinical
      research have bridged the disconnect between researchers and stakeholders,
      resulting in improved research goals with relevant outcomes, increased clinical
      trial enrollment, and improved communication of research results. This article
      focuses on the mechanisms, challenges, and benefits of patient and stakeholder
      engagement, with strategies for improvement. The 3 stages of clinical research
      and key iterative steps to create a reciprocal relationship are presented.
      Despite recent advances in stakeholder engagement, additional investigation and
      improved reporting of methods will facilitate strong reciprocal relationships
      between researchers and stakeholders.

PMID- 30213412
TI  - Health-Related Quality of Life: The Impact on Morbidity and Mortality.
AB  - In the age of ever-expanding treatments and precision medicine, the hope for cure
      remains the ultimate goal for patients and providers. Equally important to many
      patients is the quality of life achieved during and after treatment. Evidence
      suggests that overall quality of life is important to patients and plays a role
      in determining outcomes in patients with cancer. This article examines components
      of health-related quality of life and cancer treatment, including physical,
      psychosocial, and financial burden, as well as how these components affect
      patients' overall wellbeing and survival.

PMID- 30213413
TI  - Regionalization and Its Alternatives.
AB  - This article begins by introducing the historical background surrounding the
      volume-outcomes relationship literature, particularly in complex cancer surgery.
      The state of evidence surrounding mortality, as well as other outcomes, in
      relation to both hospital and surgeon procedure volume is synthesized. Where it
      is understood, the level of adoption of regionalization of various complex
      surgeries in the United States is also presented. Various controversies are
      weighed and discussed. Finally, various models of regionalization and proposed
      alternatives to regionalization from the peer-reviewed literature are presented.

PMID- 30213414
TI  - Malignant Bowel Obstruction: Reappraising the Value of Surgery.
AB  - Urgent palliative surgery in the setting of advanced malignancy is associated
      with significant morbidity, mortality, and cost. Malignant bowel obstruction is
      the most frequent indication for such intervention. Traditional surgical dogma is
      often invoked to justify associated risks and cost, but little evidence exists to
      support surgical over nonsurgical approaches. Evolving evidence may provide more
      meaningful guidance for treatment selection.

PMID- 30213415
TI  - The Accountable Care Organization for Surgical Care.
AB  - Rising health care costs superimposed on uncertainty surrounding the relationship
      between health care spending and quality have resulted in an urgent need to
      develop strategies to better align health care payment with value. Such
      approaches, at least in theory, work to achieve the dual aims of reducing growth
      in health care spending and improving population health. To date, surgery has not
      been prioritized in accountable care organizations (ACOs). Nonetheless, it is
      critically important to begin to consider strategic and impactful mechanisms
      through which surgery can be seamlessly woven into innovative population health
      models.

PMID- 30213416
TI  - Expanding the Scope of Evidence-Based Cancer Care.
AB  - This article explores how oncology research can be expanded to ensure that
      research spending results in maximum benefit. The focus has shifted to the value
      and quality of care, which view cancer care with the perspective of the patient
      at the center and cover the spectrum of care. Because there is no agreed-upon
      definition for value in cancer care, we overview various contributions to
      defining value and quality in oncology. We outline how cancer care costs are
      measured in the United States and explore outcome measures that have been
      proposed and implemented to enable us to assess value in oncology.

PMID- 30213417
TI  - Quality in a Shifting Payment Landscape and the Implications for Surgical
      Oncology.

PMID- 30213418
TI  - Measuring Quality in a Shifting Payment Landscape: Implications for Surgical
      Oncology.

PMID- 30213419
TI  - Evaluation of measurement variability in quantitative analyses: Application to
      dynamic contrast-enhanced MRI histogram analysis in rectal cancer.

PMID- 30213421
TI  - Introduction: An Overview.
AB  - The use of biologicals for clinical use is rapidly increasing. One of the logical
      questions is what constitutes a biological? The official definition of biological
      products by the Food and Drug Administration is "Biological products can be
      composed of sugars, proteins, or nucleic acids, or a combination of these
      substances. They may also be living entities, such as cells and tissues.
      Biologics are made from a variety of natural resources-human, animal, and
      microorganism-and may be produced by biotechnology methods."

PMID- 30213422
TI  - How to Use Oral and Topical Cosmeceuticals to Prevent and Treat Skin Aging.
AB  - Skin aging is caused by DNA damage in nuclei and mitochondria, inflammation,
      glycation, decreased function of keratinocytes and fibroblasts and breakdown of
      heparan sulfate, hyaluronic acid, collagen, and elastin. Identifying patients at
      an increased risk of skin aging using a standardized methodology to diagnose the
      Baumann Skin Type will allow doctors to prescribe an efficacious antiaging skin
      care regimen. Cosmeceuticals can activate LGR6+ stem cells, improve cell response
      to signals such as growth factors, stimulate collagen genes, neutralize free
      radicals, and decrease breakdown of collagen and elastin. Giving written
      instructions will increase patient compliance and improve outcomes.

PMID- 30213420
TI  - Assessment of Novel Antioxidant Therapy in Atherosclerosis by Contrast Ultrasound
      Molecular Imaging.
AB  - BACKGROUND: Ultrasound molecular imaging was used to evaluate the therapeutic
      effects of antioxidant therapy with EUK-207, which has superoxide dismutase and
      catalase activities, on suppressing high-risk atherosclerotic features. METHODS:
      Mice with age-dependent atherosclerosis produced by deletion of the low-density
      lipoprotein receptor and Apobec-1 were studied at 20 and 40 weeks of age. EUK-207
      or vehicle was administered for the preceding 8 weeks. Therapy for 28 weeks was
      also studied for 40-week-old mice. Ultrasound molecular imaging of the thoracic
      aorta was performed with contrast agents targeted to endothelial P-selectin, von
      Willebrand factor A1-domain, and platelet glycoprotein Ibalpha or control agent.
      Aortic plaque area and macrophage content were assessed by histology. RESULTS: In
      20-week-old double-knockout mice, EUK-207 compared with sham therapy produced
      only nonsignificant trends for reduction in molecular imaging signal for
      endothelial P-selectin, von Willebrand factor A1-domain, and platelet adhesion.
      At 40 weeks, EUK-207 given for 8 or 28 weeks significantly (P < .05) reduced
      signal for all three endothelial-associated events essentially to background
      levels, with the exception of glycoprotein Ibalpha signal after 8 weeks (P =
      .06). On aortic histology, EUK-207 therapy for 8 weeks did not affect plaque area
      or macrophage content at either age. However, EUK-207 for 28 weeks almost
      completely suppressed plaque development (350 +/- 258 vs 4 +/- 6 * 103 MUm2, P =
      .014) and macrophage content (136 +/- 103 vs 3 +/- 2 * 103 MUm2, P = .002)
      compared with control mice at 40 weeks. CONCLUSIONS: Molecular imaging can be
      used to assess vascular responses to antioxidants and has demonstrated that
      certain antioxidants reduce vascular endothelial activation and platelet
      adhesion, but reductions in plaque size and macrophage content occurs only with
      long-duration therapy that is started early.

PMID- 30213423
TI  - Hair Biology: Growth and Pigmentation.
AB  - Healthy hair is vital to identity. Understanding the intricate anatomy and
      physiology of hair provides insight into the aging process and the eventual loss
      of either hair pigmentation or hair shafts. Several biologics are available that
      have enabled altering or slowing the aging process of hair, but, unfortunately,
      no agent exists that can reverse the natural course. The commonly used biologics
      are discussed.

PMID- 30213424
TI  - Stem Cells in Dermatology and Anti-aging Care of the Skin.
AB  - Multipotent stem cells have paved the way for new applications and deeper
      understanding in regenerative medicine and the pathophysiology of aging. During
      skin aging, cumulative photodamage, exhaustion of endogenous stem cell
      populations, mechanical stress, and increased fibrosis lead to skin with
      decreased epidermal thickness and compromised dermal integrity. Specific stem
      cells in the hair follicle create new keratinocytes after activation by defensin
      peptides, released by neutrophils during wounding. Studies pertaining to defensin
      peptides' efficacy on skin aging have been published, highlighting their
      potential as a new therapy for skin rejuvenation.

PMID- 30213425
TI  - Platelet-Rich Plasma for Skin Rejuvenation and Tissue Fill.
AB  - Platelet preparations, including platelet-rich plasma and platelet-rich fibrin
      matrix, have been used to improve wound healing, recovery time, and cosmetic
      outcomes for facial rejuvenation. Bioactive growth factors released from
      platelets are the putative agents in producing a reparative tissue reaction in
      the treated area. Different methods of processing the patients' blood will yield
      different types of platelet preparations with different components and
      properties, and it is important to understand these differences and their
      potential implications. More robust studies are necessary to better understand
      the nuances of these preparations and their optimal use.

PMID- 30213426
TI  - Microneedling with Biologicals: Advantages and Limitations.
AB  - Microneedling is a popular and cost-effective treatment with little down time.
      The application of topical agents to enhance outcomes is common practice.
      Microchannels created with nonthermal needling close at 4 hours to 6 hours due to
      fibrin plugs. Channels created with thermal needling or fractional laser stay
      open longer and enhance drug or biological uptake more due to the dermal sponge
      injury pattern that is created. Nonthermal microneedling devices may need Food
      and Drug Administration clearance, which also notes that dermaceuticals should be
      considered drugs in many cases.

PMID- 30213427
TI  - Lasers, Microneedling, and Platelet-Rich Plasma for Skin Rejuvenation and Repair.
AB  - Skin resurfacing for the purpose of rejuvenation and repair continues to evolve
      with the development of noninvasive or minimally invasive surgical substitutes.
      Advances in laser therapy, microneedling, and platelet-rich plasma have
      reinvigorated research in wound repair and regenerative science. An overall
      positive clinical response toward the use of platelet-rich plasma as an adjuvant
      to fractional photothermolysis and percutaneous collagen induction is observed.
      Its effect on post-treatment adverse symptoms, erythema, edema, crusting, and
      clinical outcomes in rejuvenation are summarized in this article. The lack of
      identifiable complications and convenience of treatment provides a positive
      outlook for future use and investigations.

PMID- 30213428
TI  - Platelet-Rich Plasma for Hair Loss: Review of Methods and Results.
AB  - Given substantial advances in hair regrowth research and platelet-rich plasma
      (PRP) science, a review of currently used systems and results is informative for
      physicians using a biologics approach to hair restoration. Overall positive
      clinical response to the use of PRP in androgenetic and alopecia areata patients
      is observed. The effects on hair density, count, and thickness were demonstrated
      through multiple clinical trials. Use as an adjunct to hair transplantation and
      with other technologies is also described. When compared with traditional
      oral/topical treatments, the lack of identifiable complications and convenience
      of treatment provide a positive outlook for future use and investigation.

PMID- 30213429
TI  - Mesothelial Stem Cells and Stromal Vascular Fraction: Use in Functional
      Disorders, Wound Healing, Fat Transfer, and Other Conditions.
AB  - Autologous human fat-derived mesenchymal stem cells are present in stromal
      vascular fraction. Stromal vascular fraction can be easily and safely extracted
      from lipoaspirate. The regenerative, antiinflammatory and immunomodulatory
      effects of stromal vascular fraction are being documented in ongoing therapeutic
      response studies.

PMID- 30213430
TI  - Mesenchymal Stem Cells and Stromal Vascular Fraction for Hair Loss: Current
      Status.
AB  - The current state of the applicability of cell therapy for the treatment of
      various conditions of hair loss reveals a promising and potentially effective
      role. Further research, based on published work to date, is indicated to further
      explore the potential roles of autologous fat grafting, mesenchymal stem cells,
      and stromal vascular fraction therapy. The authors' evolving experience matches
      these promising scientific findings.

PMID- 30213431
TI  - Mesothelial Stem Cells and Stromal Vascular Fraction for Skin Rejuvenation.
AB  - The use of stem cells in regenerative medicine and specifically facial
      rejuvenation is thought provoking and controversial. Today there is increased
      emphasis on tissue engineering and regenerative medicine, which translates into a
      need for a reliable source of stem cells in addition to biomaterial scaffolds and
      cytokine growth factors. Adipose tissue is currently recognized as an accessible
      and abundant source for adult stem cells. Cellular therapies and tissue
      engineering are still in their infancy, and additional basic science and
      preclinical studies are needed before cosmetic and reconstructive surgical
      applications can be routinely undertaken and satisfactory levels of patient
      safety achieved.

PMID- 30213432
TI  - Biologic Treatments Are Our Future, but a More Regulated One.

PMID- 30213433
TI  - Author's reply.

PMID- 30213434
TI  - Predicting early recurrence of hepatocellular carcinoma with texture analysis of
      preoperative MRI: a radiomics study.
AB  - AIM: To investigate the feasibility of using texture analysis in preoperative
      magnetic resonance imaging (MRI) to predict early recurrence (ER) in
      hepatocellular carcinoma (HCC) post-curative surgery. MATERIAL AND METHODS:
      Institutional review board was obtained. A retrospective review of all patients
      who underwent hepatectomy between 1 January 2007 and 31 December 2015 was
      performed. Inclusion criteria included preoperative MRI, tumour size >=1 cm, new
      cases of HCC. Exclusion criteria included loss to follow-up, ruptured HCCs,
      movement artefacts, and previous hepatectomy or interval adjuvant therapy.
      Patients were divided into ER and late or no recurrence (LNR) groups. ER was
      defined as new foci of HCC within 730 days of curative surgery. Radiomics feature
      extraction was performed on T2, diffusion-weighted imaging (DWI), T1 arterial,
      and T1 portovenous acquisitions on MATLAB (Mathworks, Matick, MA, USA). The MaZda
      software was used to analyse 290 texture parameters and PRTools was used for
      feature selection. RESULTS: Fifty patients (43 male, mean age 67 years) were
      divided into ER (n=20) and LNR (n=30) groups. Serum alpha-fetoprotein level
      (p=0.026), serum gamma-glutamyltranspeptidase (p=0.014), Child-Pugh score
      (p=0.02) and the presence of vascular invasion (gross and/or microvascular,
      p=0.025) were found to be statistically significant different between the two
      groups. Parameters S(4,0)SumVarnc, S(0,3)SumOfSqs, and S(1,1)DifVarnc of the
      equilibrium phase were most accurate, achieving 84%, 82%, and 78% accuracy,
      respectively. CONCLUSION: Texture analysis of preoperative MRI has the potential
      to predict ER of HCC with up to 84% accuracy using an appropriate, single texture
      analysis parameter. Future studies are needed to validate these findings.

PMID- 30213436
TI  - Heparin-induced thrombocytopenia in cardiac surgery: Incidence, costs, and
      duration of stay.
AB  - BACKGROUND: Heparin is routinely used in many cardiovascular procedures to
      prevent thrombosis. An antibody-mediated process, heparin-induced
      thrombocytopenia occurs in a small subset of patients exposed to heparin. Though
      some have suggested a recent increase in the incidence of heparin-induced
      thrombocytopenia, data on the impact of heparin-induced thrombocytopenia on costs
      and duration of stay after cardiac surgery is generally lacking. The present
      study aimed to assess national trends in the incidence and resource use
      associated with heparin-induced thrombocytopenia in cardiac surgical patients.
      METHODS: A retrospective cohort study was performed identifying adult cardiac
      surgery patients with a diagnosis of heparin-induced thrombocytopenia by using
      the 2009-2014 National Inpatient Sample Database. Association between development
      of heparin-induced thrombocytopenia and complications during hospitalization were
      evaluated using multivariate regression models. RESULTS: Of the 3,547,883 cardiac
      surgery patients, 13,943 (0.40%) were diagnosed with heparin-induced
      thrombocytopenia. Heparin-induced thrombocytopenia was associated with
      significantly longer median index duration of stay (elective 12 vs 6 days, urgent
      17 vs 10 days; P < .001) and higher hospitalization costs (elective $56,230 vs
      $35,072, urgent $75,509 vs $42,789; P < .001). Independent predictors of heparin
      induced thrombocytopenia included female sex (elective odds ratio 1.4, 95%
      confidence interval 1.01-1.03) and history of hypercoagulable condition (elective
      odd ratio 4.03, 95% confidence interval 1.8-8.9). After adjustment for baseline
      differences, heparin-induced thrombocytopenia was independently associated with
      increased risk of mortality (elective odds ratio 2.0, 95% confidence interval 1.3
      3.1; urgent odds ratio 1.8, 95% confidence interval 1.3-2.5), neurologic
      (elective odds ratio 1.5, 95% confidence interval 1.2-1.9; urgent odds ratio 1.3,
      95% confidence interval 1.1-1.6), infectious (elective odds ratio 2.4, 95%
      confidence interval 1.9-3.0; urgent odds ratio 1.6, 95% confidence interval 1.4
      2.0), and respiratory (elective odds ratio 1.4, 95% confidence interval 1.2-1.5;
      urgent odds ratio 1.4, 95% confidence interval 1.2-1.5) complications.
      CONCLUSION: Based on this national analysis of adult cardiac surgical patients,
      the presence of heparin-induced thrombocytopenia was associated with higher odds
      of mortality and morbidity, greater costs, and longer duration of stay. Female
      gender, history of hypercoagulability, and heart failure, among others, are
      independent predictors of heparin-induced thrombocytopenia. These findings have
      significant implications in the era of value-based health care delivery. In
      addition to reducing unnecessary exposure to heparin, proper diagnosis and
      treatment are essential for favorable outcomes.

PMID- 30213437
TI  - [Social responsibility and health: A pending task].

PMID- 30213435
TI  - A practical guide for the safe implementation of early phase drug development and
      immunotherapy program in gynecologic oncology practice.
AB  - The success of targeted and immune therapies in other malignancies has led to an
      exponential increase in the number of active and pending clinical trials using
      these therapeutic approaches in patients with gynecologic cancers. These novel
      investigational agents are associated with unique and potentially life
      threatening toxicities and many require special multidisciplinary logistical
      considerations. The objective of this review is to describe a practical approach
      for the safe implementation of targeted and immune therapies in academic
      gynecologic oncology practices based on our experience at M.D. Anderson Cancer
      Center.

PMID- 30213438
TI  - Music therapy in a sleepless child with Pierre Robin sequence, partial trisomy 14
      and partial monosomy 21.

PMID- 30213440
TI  - Right Atrium Angiosarcoma: An Unexpected Cause of Stroke.

PMID- 30213439
TI  - Pulmonary Ionocytes Challenge the Paradigm in Cystic Fibrosis.
AB  - Two recent studies have identified novel airway cells termed pulmonary ionocytes
      that express higher levels of CFTR than other airway cells express. These
      findings raise new questions in the evolving debate about the physiological role
      of CFTR in lung epithelia and its importance in the pathogenesis of cystic
      fibrosis (CF).

PMID- 30213441
TI  - Severe neurologic and hepatic toxicity in a newborn prenatally exposed to
      methamphetamine. A case report.
AB  - OBJECTIVE: In the recent years the increase of methamphetamines (MTA) abusers
      women has become an emerging problem. Very little data has been published
      regarding the effects of prenatal MTA exposure. We describe a case of MTA related
      toxicity in a term newborn which have early onset of neonatal encephalopathy and
      liver failure. CASE REPORT: A term infant born to a MTA abuser mother developed
      seizures and severe neurological symptoms shortly after birth. Methamphetamine
      was detected both in maternal and in neonatal urine. The laboratoristic tests
      revealed severe hepatic insufficiency, coagulopathy and thrombocytopenia. Due to
      neonatal encephalopathy the newborn underwent hypothermia. Phenobarbital, fresh
      frozen plasma, platelet transfusions and vitamin K were administered. Cranial
      ultrasonography and magnetic resonance imaging (MRI) showed diffuse white matter
      damage and two ischemic-hemorrhagic cerebral lesions. Gradually the clinical
      conditions improved, at 1 month MRI showed a stabilization of cerebral lesions
      with residual diffuse leukomalacia. Physiotherapy and neurological follow up is
      ongoing to evaluate the long term effects. CONCLUSIONS: although infrequent, MTA
      related toxicity should be suspected in infants with neurologic and hepatic
      symptoms. Further studies are warranted to confirm our findings in order to
      identify newborns at high risk of acute MTA toxicity in time to provide them the
      appropriate support.

PMID- 30213442
TI  - Aggregate formation analysis of GFAPR416W found in one case of Alexander disease.
AB  - Alexander disease (AxD) is a neurodegenerative disease in astrocytes caused by a
      mutation in the gene encoding glial fibrillary acidic protein, GFAP. We herein
      present the case of a 12-year-old girl who showed intermittent exotropia at 3
      years of age and central precocious puberty at 7 years of age. The
      periventricular and medulla oblongata showed high signal intensity on T2-weighted
      magnetic resonance imaging. The patient was diagnosed with AxD after direct
      sequencing revealing a de novo recurrent mutation, c.1246C>T (p.R416W) in GFAP.
      The transient expression of GFAPR416W in cells resulted in the significant
      formation of aggregates, which recapitulated the hallmark of AxD. We firstly
      utilized In Cell analyzer to prove the tendency of aggregate formation by mutants
      of GFAP.

PMID- 30213443
TI  - Efficacy of the anti-IL 17 secukinumab in refractory Behcet's syndrome: A
      preliminary study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of secukinumab in Behcet's
      patients with active mucocutaneous and articular manifestations refractory to
      previous treatments. METHODS: We retrospectively evaluated 5 patients treated
      with the IL17-inhibitor secukinumab and diagnosed with Behcet according to
      ISG/ICBD criteria. All patients had active mucocutaneous and articular
      manifestations refractory to colchicine, conventional DMARDs and at least one
      anti-TNFalpha agent. Four patients received secukinumab in the dose of 150
      mg/monthly since also fulfilling the criteria for ankylosing spondylitis, while
      the fifth patient received secukinumab 300 mg/monthly because she met psoriatic
      arthritis criteria. Achievement of response was based on the number of oral
      ulcers, BASDAI and ASDAS for articular involvement, and BDCAF for Behcet
      activity. Complete response was defined as: i) decrease >=50% in the number of
      oral ulcers; ii) BASDAI index <4; iii) ASDAS index <1.4; iv) decrease of 50% or
      more in BDCAF index. RESULTS: The patient starting secukinumab 300 mg/month
      successfully achieved complete response within 3 months. Complete response was
      maintained during all 9-months follow-up. Among the 4 subjects starting
      secukinumab 150 mg/month, two achieved complete response at month 6, but one
      relapsed. This patient and the two who not achieved complete response at month 6
      were switched to secukinumab 300 mg/month. Within 3 months from the dosage
      increase, all three subjects successfully (re)achieved complete response.
      CONCLUSION: Our study suggested for the first time that secukinumab (either 150
      mg and 300 mg/month) improved active mucocutaneous manifestations refractory to
      previous treatments, while secukinumab 300 mg/monthly resulted superior in
      inducing articular and complete response in Behcet's patients.

PMID- 30213444
TI  - Characteristics of breath sound in infants with risk factors for asthma
      development.
AB  - BACKGROUND: Breath sound parameters have been suggested as biomarkers of the
      airway narrowing in children. Using a commercially available breath sound
      analyzer, the characteristics of the airway condition were investigated in
      infants with the risk factors for asthma development. METHODS: A total of 443
      infants (mean age, 9.9 months; range, 3-24 months) were included in the present
      study. The breath sound parameters of the frequency limiting 99% of the power
      spectrum (F99), the roll-off from 600 to 1200 Hz (Slope) and spectrum curve
      indices, the total area under the curve of the dBm data (A3/AT) and the ratio of
      power and frequency at 50% and 75% of the highest frequency of the power spectrum
      (RPF75 and RPF50), were evaluated. Using an ATS-DLD based original Japanese
      questionnaire, we examined the characteristics of airway condition of infants.
      RESULTS: Finally, 283 infants in good health were included in the present study.
      The RPF75, RPF50, Slope and F99 in infants with positive results of allergy and
      atopic dermatitis were significantly increased more than those in the infants
      with negative result. CONCLUSIONS: Our data highlight the characteristics of
      breath sounds in infants with risk factors for asthma. The breath sound analysis
      may be useful for assessing the airways of infants for asthma development.

PMID- 30213446
TI  - Improving visualization of trace components for quantification using a power law
      based integration approach.
AB  - In some cases, trace component analysis only requires a sensitive and high
      resolution mass spectrometer. However, enantiomers must be completely separated
      to be differentiated with a mass spectrometer, which is highly dependent on the
      stationary-mobile phase composition. In case of a challenging chiral separation,
      instead of trying new columns for screening purpose, resolution enhancement
      techniques could be used to resolve partially overlapping peaks. A well-known
      enhancement method is the power law, which increases the linear dynamic range of
      each analyte and reduces excessive noise. In many cases, the peak noise can
      decrease significantly by applying the power law. However, the main drawback is
      that this approach changes relative peak areas and heights of each peak in a non
      linear fashion which limits its use for quantitative purposes. In this study, a
      normalized power law was utilized for extracting correct area information. It is
      a simple (5 step) protocol that only requires Microsoft Excel, and results in
      enhanced visualization of trace components, especially in low signal/noise
      environments, and makes integration convenient and reproducible. Several
      difficult chiral trace component analyses were investigated, including
      applications pertaining to ultrafast high-throughput chromatography,
      enantiopurity, and peak purity analysis. For complicated cases with multiple
      overlapped peaks of different resolutions, a segmented normalized power law was
      utilized. A trace component coeluting near a dead volume peak and a trace
      enantiomeric component in the tail of the corresponding enantiomeric peak were
      virtually enhanced. As an additional tool, first and second derivatives were
      utilized to identify if an enantiomeric impurity is coeluting with the dominant
      enantiomer under overload conditions. Idiosyncrasies of the derivative test are
      discussed. This study shows how these simple approaches can be used for accurate
      quantitation, specifically for trace enantiomeric components.

PMID- 30213445
TI  - Surgical treatment and prognosis of adult patients with brainstem gliomas.
AB  - The paper presents 47 adult patients who were surgically treated due to brainstem
      gliomas. Thirteen patients presented with contrast-enhancing Grades III and IV
      gliomas, according to the WHO classification, 13 patients with contrast-enhancing
      tumours originating from the glial cells (Grade I; WHO classification), 9
      patients with diffuse gliomas, 5 patients with tectal brainstem gliomas and 7
      patients with exophytic brainstem gliomas. During the surgical procedure,
      neuronavigation and the diffusion tensor tractography (DTI) of the corticospinal
      tract were used with the examination of motor evoked potentials (MEPs) and
      somatosensory evoked potentials (SSEPs) with direct stimulation of the fundus of
      the fourth brain ventricle in order to define the localization of the nuclei of
      nerves VII, IX, X and XII. Cerebellar dysfunction, damage to cranial nerves and
      dysphagia were the most frequent postoperative sequelae which were also the most
      difficult to resolve. The Karnofsky score established preoperatively and the
      extent of tumour resection were the factors affecting the prognosis. The mean
      time of progression-free survival (14 months) and the mean survival time after
      surgery (20 months) were the shortest for malignant brainstem gliomas. In the
      group with tectal brainstem gliomas, no cases of progression were found and none
      of the patients died during the follow-up. Some patients were professionally
      active. Partial resection of diffuse brainstem gliomas did not prolong the mean
      survival above 5 years. However, some patients survived over 5 years in good
      condition.

PMID- 30213447
TI  - Sigmapider diagram: A universal and versatile approach for system comparison and
      classification. Part 2: Stationary phase properties.
AB  - Many different sorts of bonded phase chemistries may be used in high-performance
      liquid chromatography (HPLC) in the reversed-phase mode: C8, C18 (type A or B),
      polar-embedded C18, phenyl, pentafluorophenyl, or cyanopropyl. To assess their
      retention and selectivity properties, chromatographic tests exist. The data
      obtained from these tests may be presented in three ways. First, simple
      classification diagrams may be plotted, when only two or three parameters are
      studied. Secondly, chemometric treatments such as principal component analyses
      (PCA) or hierarchical cluster analyses (HCA) may be computed, when at least 4
      parameters are studied. These are sometimes uneasy to interpret. Thirdly, the
      "distance" between one column and a reference column may be estimated, through
      calculated ranking (F or CDF) or selectivity (s) factors. In this paper, another
      treatment type is applied to the data of Euerby (Tanaka test) and Snyder
      (Hydrophobic Subtraction Model), each of these tests having 6 parameters. This
      treatment produces a visual classification, called spider diagram. In the first
      part of this series, this type of classification was applied to the
      classification of solvents. A logical and easily comprehensible classification is
      obtained for the varied types of bonded phases, with a clear location, which can
      be related to the chromatographic properties. The comparison of these diagrams
      shows that the classification based on Snyder's hydrophobic subtraction model
      discriminates the stationary phases more effectively than the one based on the
      Tanaka test. Finally, on the basis of the parameter relevance and in order to
      favour comparison between these two tests and a third one called the carotenoid
      test, simplified classification maps are proposed. For Tanaka test, the selected
      parameters are the pentylbenzene retention factor (hydrophobicity), the
      benzylamine/phenol separation factor at pH 7.6 (polar surface activity) and the
      triphenylene/ortho-terphenyl (shape selectivity) separation factor. For Snyder
      test, the parameters selected are the ethylbenzene retention factor
      (hydrophobicity) the C term at pH 7.0 (polar surface activity) and the S* term
      (steric electivity). The location of some stationary phases onto the maps and
      their rankings are compared and shown to agree well between the three tests.

PMID- 30213448
TI  - Age estimation accuracies from black South African os coxae.
AB  - The accurate estimation of age is considered important from an ethical, legal and
      archaeological perspective. Among the numerous methods based on macroscopic
      skeletal studies for age estimation, the Brooks and Suchey (1990) method for
      aging from the pubic symphysis and the Buckberry and Chamberlain (2002) method
      for aging from the auricular surface are considered more reliable. However, both
      these methods have been derived from American populations. Therefore, the
      following study aimed to assess the accuracy of the estimation of age-at-death
      from morphological age related changes seen on the pubic symphysis and the
      auricular surface in a black South African population. A total of 197 individuals
      of known age of both sexes using both left and right ossa coxae were
      investigated. Age was estimated using descriptions stipulated by Brooks and
      Suchey (1990) and Buckberry and Chamberlain (2002). Correlation coefficients,
      inaccuracies and bias were calculated for both skeletal elements for both sexes
      and sides. Inaccuracies and bias were lower in the pubic symphysis than in the
      auricular surface thus making the pubic symphysis a more reliable age estimator.
      Similarly, males indicated lower inaccuracies and bias than did females. Overall,
      the pubic symphysis outperformed the auricular surface, even though the method
      described by Buckberry and Chamberlain (2002) is considered more reliable. It is
      advised that these two methods be improved to produce better accuracies,
      particularly when applying the methods to a black South African population.

PMID- 30213450
TI  - Quality of life is not compromised with intensification of androgen therapy in
      recurrent prostate cancer.

PMID- 30213449
TI  - Effect of apalutamide on health-related quality of life in patients with non
      metastatic castration-resistant prostate cancer: an analysis of the SPARTAN
      randomised, placebo-controlled, phase 3 trial.
AB  - BACKGROUND: In the SPARTAN trial, addition of apalutamide to androgen deprivation
      therapy, as compared with placebo plus androgen deprivation therapy,
      significantly improved metastasis-free survival in men with non-metastatic
      castration-resistant prostate cancer who were at high risk for development of
      metastases. We aimed to investigate the effects of apalutamide versus placebo
      added to androgen deprivation therapy on health-related quality of life (HRQOL).
      METHODS: SPARTAN is a multicentre, international, randomised, phase 3 trial.
      Participants were aged 18 years or older, with non-metastatic castration
      resistant prostate cancer, a prostate-specific antigen doubling time of 10 months
      or less, and a prostate-specific antigen concentration of 2 ng/mL or more in
      serum. Patients were randomly assigned (2:1) to 240 mg oral apalutamide per day
      plus androgen deprivation therapy, or matched oral placebo plus androgen
      deprivation therapy, using an interactive voice randomisation system. Permuted
      block randomisation was used according to the three baseline stratification
      factors: prostate-specific antigen doubling time (>6 months vs <=6 months), use
      of bone-sparing drugs (yes vs no), and presence of local-regional nodal disease
      (N0 vs N1). Each treatment cycle was 28 days. The primary endpoint was metastasis
      free survival. The trial was unblinded in July, 2017. In this prespecified
      exploratory analysis we assessed HRQOL using the Functional Assessment of Cancer
      Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaires, which we collected at
      baseline, day 1 of cycle 1 (before dose), day 1 of treatment cycles 1-6, day 1 of
      every two cycles from cycles 7 to 13, and day 1 of every four cycles thereafter.
      This study is registered with ClinicalTrials.gov, number NCT01946204. FINDINGS:
      Between Oct 14, 2013, and Dec 15, 2016, we randomly assigned 1207 patients to
      receive apalutamide (n=806) or placebo (n=401). The clinical cutoff date, as for
      the primary analysis, was May 19, 2017. Median follow-up for overall survival was
      20.3 months (IQR 14.8-26.6). FACT-P total and subscale scores were associated
      with a preservation of HRQOL from baseline to cycle 29 in the apalutamide group;
      there were similar results for EQ-5D-3L. At baseline, the mean for FACT-P total
      score in both the apalutamide and placebo groups were consistent with the FACT-P
      general population norm for US adult men. Group mean patient-reported outcome
      scores over time show that HRQOL was maintained from baseline after initiation of
      apalutamide treatment and was similar over time among patients receiving
      apalutamide versus placebo. Least-squares mean change from baseline shows that
      HRQOL deterioration was more apparent in the placebo group. INTERPRETATION: In
      asymptomatic men with high-risk non-metastatic castration-resistant prostate
      cancer, HRQOL was maintained after initiation of apalutamide treatment.
      Considered with findings from SPARTAN, patients who received apalutamide had
      longer metastasis-free survival and longer time to symptomatic progression than
      did those who received placebo, while preserving HRQOL. FUNDING: Janssen Research
      & Development.

PMID- 30213451
TI  - Camrelizumab for nasopharyngeal carcinoma: a new hope?

PMID- 30213452
TI  - Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin
      for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials.
AB  - BACKGROUND: Platinum-based doublet chemotherapy regimens, preferentially
      gemcitabine plus cisplatin, are generally considered the first-line standard of
      care for patients with recurrent or metastatic nasopharyngeal carcinoma. However,
      no consensus has been reached regarding treatment following progression after
      first-line therapy. Camrelizumab (SHR-1210) is a humanised anti-programmed death
      1 (anti PD-1) antibody. We present safety and preliminary antitumour activity of
      camrelizumab alone as second-line therapy in patients with recurrent or
      metastatic nasopharyngeal carcinoma and combined with gemcitabine and cisplatin
      as first-line therapy in this patient population. METHODS: We report the results
      from two single-arm, phase 1 trials. Both trials included patients aged 18-70
      years with histologically or cytologically confirmed nasopharyngeal carcinoma and
      confirmed metastatic disease or locoreginal recurrence, and an Eastern
      Cooperative Oncology Group performance status of 0 or 1. Patients who received at
      least one previous line of treatment were enrolled at five academic hospitals in
      China into the dose-escalation and expansion trial to receive camrelizumab
      monotherapy intravenously at escalating doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg,
      and a bridging dose of 200 mg per dose once every 2 weeks (monotherapy trial).
      Treatment-naive patients were enrolled from a single centre in China to receive
      six cycles of camrelizumab 200 mg (day 1), gemcitabine 1 g/m2 (days 1 and 8), and
      cisplatin 80 mg/m2 (day 1) every 3 weeks followed by camrelizumab 200 mg
      maintenance once every 3 weeks (combination trial). The primary endpoint of both
      trials was the safety and tolerability of the study treatment. Analyses were done
      per protocol. Both trials are registered with ClinicalTrials.gov, number
      NCT02721589 (camrelizumab monotherapy trial) and NCT03121716 (camrelizumab
      combination trial). Both trials are ongoing, but are no longer enrolling
      patients. FINDINGS: In the camrelizumab monotherapy trial, between March 31,
      2016, and Sept 20, 2017, 121 patients were assessed for eligibility, of whom 93
      patients were enrolled across the dose-escalation and expansion cohorts and
      received at least one dose of camrelizumab (safety population). 15 (16%) of 93
      patients had treatment-related adverse events of grade 3 or 4, the most common of
      which were elevated conjugated bilirubin concentration (three [3%] of 93
      patients), stomatitis, anaemia, and increased concentrations of aspartate
      aminotransferase, alanine aminotransferase, and total bilirubin, each of which
      occurred in two (2%) patients. Eight (9%) patients had a treatment-related
      serious adverse event. No dose-limiting toxic effects were observed during the
      dose-escalation phase. 31 (34%; 95% CI 24-44) of 91 evaluable patients on
      camrelizumab monotherapy had an overall response with a median follow-up of 9.9
      months (IQR 8.1-11.7). In the camrelizumab combination trial, between April 18,
      2017, and Aug 15, 2017, 24 patients were assessed for eligibility, of whom 23
      patients were enrolled and treated (safety population). 20 (87%) of 23 patients
      had grade 3 or 4 treatment-related adverse events: neutropenia (13 [57%] of 23
      patients), anaemia (11 [48%] patients), leucopenia (11 [48%] patients),
      thrombocytopenia (seven [30%] patients), oedema (two [9%] patients),
      hyponatraemia (two [9%] patients), hypochloraemia (one [4%] patients), and rash
      (one [4%] patient). Two patients had treatment-related serious adverse events. No
      treatment-related deaths occurred in these trials. 20 (91% [95% CI 72-97]) of 22
      evaluable patients had an overall response with a median follow-up time of 10.2
      months (IQR 9.7-10.8). INTERPRETATION: Camrelizumab is a well tolerated,
      potential treatment option for patients with recurrent or metastatic
      nasopharyngeal carcinoma. The combination of camrelizumab plus gemcitabine and
      cisplatin has a manageable toxicity profile and promising preliminary antitumour
      activity for this disease in treatment-naive patients. Randomised controlled
      trials are needed to further establish the role of immune checkpoint inhibition
      for nasopharyngeal carcinomas. FUNDING: Hengrui Medicine Co, Chinese National
      Natural Science Foundation project, Science and Technology Program of Guangdong,
      Pearl River Nova Program of Guangzhou.

PMID- 30213454
TI  - Medical decision making for older patients during multidisciplinary oncology team
      meetings.
AB  - OBJECTIVES: Multidisciplinary team meetings aim to facilitate efficient and
      accurate communication surrounding the complex process of treatment decision
      making for older patients with cancer. This process is even more complicated for
      older (>=70 years) patients as the lack of empirical evidence on treatment
      regimens in patients with age-related problems such as comorbidity and
      polypharmacy, necessitates a patient-centred approach.This study investigates the
      decision making process for older patients with cancer during multidisciplinary
      team meetings and the extent to which geriatric evaluation and geriatric
      expertise contribute to this process. METHODS: Non-participant observations of
      171 cases (>=70 years) during 30 multidisciplinary team meetings in five
      hospitals and systematically analysed using a medical decision making framework.
      All cases were in patients with colon or rectal cancer. RESULTS: First, not all
      steps from the medical decision making framework were followed. Second, we found
      limited use of patient-centred information such as (age-related) patient
      characteristics and patient preferences during the decision making process.
      Third, a geriatric perspective was largely missing in multidisciplinary team
      meetings. CONCLUSIONS: This study uncovers gaps in the treatment decision making
      process for older patients with cancer during multidisciplinary team meetings. In
      particular individual vulnerabilities and patient wishes are often neglected.

PMID- 30213453
TI  - Protein- and Peptide-Based Biosensors in Artificial Olfaction.
AB  - Animals' olfactory systems rely on proteins, olfactory receptors (ORs) and
      odorant-binding proteins (OBPs), as their native sensing units to detect odours.
      Recent advances demonstrate that these proteins can also be employed as molecular
      recognition units in gas-phase biosensors. In addition, the interactions between
      odorant molecules and ORs or OBPs are a source of inspiration for designing
      peptides with tunable odorant selectivity. We review recent progress in gas
      biosensors employing biological units (ORs, OBPs, and peptides) in light of
      future developments in artificial olfaction, emphasizing examples where
      biological components have been employed to detect gas-phase analytes.

PMID- 30213455
TI  - Balancing the risks and benefits of antipsychotic medications for symptom
      management in older patients with cancer.

PMID- 30213456
TI  - Hydrological buffering during groundwater acidification in rapidly
      industrializing alluvial plains.
AB  - Shallow groundwater in alluvial plains is vulnerable to contamination due to
      infiltration of pollutants from anthropogenic activities. In the alluvial plain
      of the Yangtze River near Poyang Lake, a silicone monomer industrial park was
      found to discharge undisclosed amount of effluents containing high levels of
      hydrochloric acid and total dissolved solids into ponds and ditches that in turn,
      displayed characteristics of acidic water with high total dissolved solids.
      However, most shallow groundwater (n = 35, depth 5.5-22 m) collected from the
      alluvial aquifer downgradient of the industrial park contained low Cl- (< 59
      mg/L). Only 4 groundwater samples showed high Cl- (59-790 mg/L) with two
      containing superlative levels (449 mg/L and 790 mg/L) located within a 50 m
      distance from the polluted ponds and ditches. In addition to hydrochemical data,
      modeling was used to explain why a highly vulnerable alluvial aquifer was not
      more contaminated when subjected to such intense point source pollution and to
      estimate the effluent discharge. Flow and solute transport modeling suggests that
      a hydrological buffering mechanism resulting from a topography driven groundwater
      outflow along the boundary between the Pleistocene (Qpw) and the Holocene (Qhl)
      aquifers where the polluted ponds and ditches are fortuitously located has
      restricted acid infiltration, with only a few percent of the estimated acid
      discharge in the amount of 1700-4200 tons per year entering the aquifer. Our
      model results show that pumping from the upland Qpw aquifer breaks this
      hydrological buffering much more easily than pumping from the downgradient Qhl
      aquifer, suggesting the vulnerability of this buffering mechanism thus
      compromising groundwater utilization in the future.

PMID- 30213457
TI  - Retrospective cost-effectiveness of the 23-valent pneumococcal polysaccharide
      vaccination program in Australia.
AB  - BACKGROUND: The Australian infant pneumococcal vaccination program was funded in
      2005 using the 7-valent pneumococcal conjugate vaccine (PCV7) and the 13-valent
      conjugate vaccine (PCV13) in 2011. The PCV7 and PCV13 programs resulted in herd
      immunity effects across all age-groups, including older adults. Coincident with
      the introduction of the PCV7 program in 2005, 23-valent pneumococcal
      polysaccharide vaccine (PPV23) was funded for all Australian adults aged over 65
      years. METHODS: A multi-cohort Markov model with a cycle length of one year was
      developed to retrospectively evaluate the cost-effectiveness of the PPV23
      immunisation program from 2005 to 2015. The analysis was performed from the
      healthcare system perspective with costs and quality-adjusted life years
      discounted at 5% annually. The incremental cost-effectiveness ratio (ICER) for
      PPV23 doses provided from 2005 to 2015 was calculated separately for each year
      when compared to no vaccination. Parameter uncertainty was explored using
      deterministic and probabilistic sensitivity analysis. RESULTS: It was estimated
      that PPV23 doses given out over the 11-year period from 2005 to 2015 prevented
      771 hospitalisations and 99 deaths from invasive pneumococcal disease (IPD).
      However, the estimated IPD cases and deaths prevented by PPV23 declined by more
      than 50% over this period (e.g. from 12.9 deaths for doses given out in 2005 to
      6.1 in 2015), likely driven by herd effects from infant PCV programs. The
      estimated ICER over the period 2005 to 2015 was approximately A$224,000/QALY
      gained compared to no vaccination. When examined per year, the ICER for each
      individual year worsened from $140,000/QALY in 2005 to $238,000/QALY in 2011 to
      $286,000/QALY in 2015. CONCLUSION: The cost-effectiveness of the PPV23 program in
      older Australians was estimated to have worsened over time. It is unlikely to
      have been cost-effective, unless PPV23 provided protection against non-invasive
      pneumococcal pneumonia and/or a low vaccine price was negotiated. A key policy
      priority should be to review of the future use of PPV23 in Australia, which is
      likely to be more cost-effective in certain high-risk groups.

PMID- 30213458
TI  - Ultrasound-assisted synthesis of highly functionalized benzo[1,3]thiazine via Cu
      catalyzed intramolecular CH activation reaction from isocyanides, aniline
      benzoyl(acetyl) isothiocyanate adduct.
AB  - A facile sonochemical route for the synthesis of benzo[1,3]thiazine derivatives
      via a one pot, multicomponent, intramolecular CH activation reaction from
      isocyanides, aniline and benzoyl (acetyl) isothiocyanate adduct catalyzed by
      copper (I) iodide in acetone at 30  degrees C have been reported. The advantages
      of the described method include using simple and readily available starting
      materials and performing under mild copper-catalytic reaction conditions and also
      obtaining pure product with high yield without applying column chromatography.
      Furthermore, using the sonochemical methodology as an efficient method led to
      reduce the reaction times.

PMID- 30213459
TI  - Cord Blood Metabolites Associated with Newborn Adiposity and Hyperinsulinemia.
AB  - OBJECTIVE: To evaluate the association between cord blood amino acid and
      acylcarnitine profiles and measures of adiposity and hyperinsulinemia in healthy
      newborns. STUDY DESIGN: A cross-sectional study of 118 full-term infants born to
      mothers without gestational diabetes was performed. Cord blood leptin, C-peptide,
      acylcarnitine, and amino acid levels were measured. Body composition was measured
      by air displacement plethysmography. Multivariate linear regression and principal
      component analysis were used to analyze associations of cord blood metabolites
      with newborn anthropometrics, leptin, and C-peptide. RESULTS: Acylcarnitines AC
      C2, AC C4-DC/Ci4-DC, and AC C8:1-OH/C6:1-DC were positively associated with
      leptin, and AC C14, AC C14:2, AC C16, AC C18, and AC C18:2 were negatively
      associated with C-peptide (P <= .0016). Principal component analysis revealed a
      positive association between factor 1(AC C2, AC C3, AC C5, AC C4/Ci4, AC C4-OH,
      AC C4-DC/Ci4-DC, glutamate/glutamine, and glycine) and adiposity measures.
      CONCLUSIONS: The positive association of AC C2 and AC C4-DC/Ci4-DC levels with
      leptin may reflect excess fat stores, higher fatty acid oxidation rate, and
      mitochondrial dysfunction leading to accumulation of acylcarnitine intermediates.
      Principal component analysis revealed a positive association between branched
      chain amino acid and ketone body metabolites and adiposity, confirming prior
      findings in adults. Cord blood acylcarnitine profiles may identify at-risk
      children before obesity or insulin resistance develops.

PMID- 30213461
TI  - Healthier Choices in School Cafeterias: A Systematic Review of Cafeteria
      Interventions.
AB  - OBJECTIVE: To describe school cafeteria interventions in terms of a behavioral
      economics scheme and to assess which system is more likely to be effective in
      improving food selection or consumption. STUDY DESIGN: With this systematic
      review, we categorize cafeteria interventions using the behavioral economics
      theory of Kahneman into system 1 (fast and intuitive thinking) and system 2 (slow
      and cognitively demanding) or mixed (having elements of system 1 and system 2).
      Pertinent studies were identified from review of the literature of interventions
      performed in school and cafeteria settings in children grades K-12 within the
      past 5 years (2012-2017) at time of search. RESULTS: In all, 48 of 978 studies
      met inclusion criteria. By defining success as a 30% improvement in a desired
      outcome or statistically significant reduction in body mass index, 89% of system
      1, 67% of mixed (had both system 1 and 2 elements), and only 33% of system 2
      interventions were successful. CONCLUSIONS: This review found successful system 1
      type school cafeteria interventions to be more common than system 2 type
      interventions and system 2 type interventions are less effective than system 1.

PMID- 30213462
TI  - Desirable quality-control materials for the establishment of qualified external
      quality assessment on prenatal diagnosis of chromosomal aneuploidies.
AB  - OBJECTIVE: To prepare desirable quality-control materials for the establishement
      of qualified external quality assessment on fluorescence in situ hybridization
      (FISH)-detected prenatal diagnosis of chromosomal aneuploidies. METHODS: Four
      types of amniotic fluid cell suspensions (13-trisomy, 18-trisomy, 21-trisomy and
      47,XXY) were mixed together by ratio to produce mosaicism with the percentages of
      each aneuploidy as 10%, 20%, 30% and 40%, respectively. After being stored in
      liquid nitrogen of -196  degrees C for six months, randomly selected samples were
      incubated in 37  degrees C water, followed by cultivation, hypo-osmosis and
      fixation. Finally, FISH detetion was applied on them before and after external
      laboratory mailing, in step with detection on conventional case samples. RESULTS:
      Before mailing, the positive rates of each aneuploidy described above were 12.8%,
      23.6%, 33.8%, 44.0%, while 12.6%, 23.8%, 34.0%, 43.5% after mailing. t-test,
      criteria for stability assessment of quality-control materials in CANS-GL03:2006,
      showed no significant effect of external mailing on mosaicism since corresponding
      t values are lower than threshold with significance level alpha as 0.05 and
      degree of freedom as 10. CONCLUSION: As FISH detection showed, the mosaic cell
      strains prepared in current study exhibited excellent stabilities after
      cryopreservation in -196  degrees C, subculture, hypo-osmosis, fixation and
      external laboratory mailing, demonstrating them as reliable and promising quality
      control materials for the establishment of a qualified external quality
      assessment on prenatal diagnosis of chromosomal aneuploidies.

PMID- 30213460
TI  - Next-Generation Evaluation and Treatment of Pediatric Acute Lymphoblastic
      Leukemia.

PMID- 30213463
TI  - Effects of Exercise Training and CPAP in Patients With Heart Failure and OSA: A
      Preliminary Study.
AB  - BACKGROUND: Exercise and CPAP improve OSA. This study examined the effects of
      exercise in patients with heart failure (HF) and OSA. METHODS: Patients with HF
      and OSA were randomized to the following study groups: control, exercise, CPAP,
      and exercise + CPAP. RESULTS: Sixty-five participants completed the protocol.
      Comparing baseline vs 3 months, the mean apnea-hypopnea index (AHI) did not
      change significantly (in events per hour) in the control group, decreased
      moderately in the exercise group (28 +/- 17 to 18 +/- 12; P < .03), and decreased
      significantly more in the CPAP group (32 +/- 25 to 8 +/- 11; P < .007) and in the
      exercise + CPAP group (25 +/- 15 to 10 +/- 16; P < .007). Peak oxygen
      consumption, muscle strength, and endurance improved only with exercise. Both
      exercise and CPAP improved subjective excessive daytime sleepiness, quality of
      life, and the New York Heart Association functional class. However, compared with
      the control group, changes in scores on the 36-item Medical Outcomes Study Short
      Form Survey and Minnesota Living with Heart Failure Questionnaire were only
      significant in the exercise groups. CONCLUSIONS: In patients with HF and OSA, our
      preliminary results showed that exercise alone attenuated OSA and improved
      quality of life more than CPAP. In the landscape treatment of OSA in patients
      with HF, this analysis is the only randomized trial showing any treatment (in
      this case, exercise) that improved all the studied parameters. The results
      highlight the important therapeutic benefits of exercise, particularly because
      adherence to CPAP is low.

PMID- 30213464
TI  - MiRNAs as molecular biomarkers in stage II egyptian colorectal cancer patients.
AB  - AIM: To assess the role of aberrant miRNAs expressions in stage II CRC patients
      from Egypt. METHODS: Tumor tissue samples were obtained from 124 CRC stage II
      patients compared to 100 healthy controls for assessing miRNAs expression using;
      1) a cataloged 84-miRNAs PCR array panel, and 2) another five miRNAs (miR-21, miR
      137, miR-145, miR-320 and miR-498) that have been reported in previous studies to
      have a role in CRC, by quantitative real time PCR (qPCR). The results were
      correlated to patients' characteristics, response to treatment and survival.
      RESULTS: There were 17 out of 84 miRNAs differentially expressed in the CRC
      patients. Twenty six miRNAs were significantly differentially expressed in the
      female CRC patients, while 16 miRNAs were significantly differentially expressed
      in the male CRC patients. Only, five miRNAs (miR-21, Let-7a-5p, miR-100-5p, miR
      200c-3p and miR-23b-3p) were significantly common deregulated in CRC patients
      regardless gender. miR-21 was overexpressed in 48.4% of the patients and it was
      significantly downregulated in females and over expressed in males. In univariate
      analysis; performance status, over-expression of miR-21 and miR-498 and reduced
      miR-137, miR-145, and miR-320 associated significantly with reduced DFS and OS
      whereas in multivariate analysis; miR-498 and miR-320 were independent prognostic
      factors for DFS and miR-21 was independent prognostic factors for OS. CONCLUSION:
      miRNAs expression differs significantly between male and female stage II CRC
      patients, miR-21, Let-7a-5p, miR-100-5p, miR-200c-3p and miR-23b-3p could be used
      as common diagnostic biomarkers for CRC. On the other hand, a three miRNAs panel
      (miR-21, miR-498 and miR-320) can predict recurrence and survival in those
      patients.

PMID- 30213465
TI  - Corrigendum to "Effects of Atorvastatin on Surgical Treatments of Chronic
      Subdural Hematoma" [World Neurosurgery 117 (2018) e425-e429].

PMID- 30213466
TI  - Rapid identification of nonblood sterile site broth cultures using the FilmArray
      blood culture identification panel.
AB  - The FilmArray Blood Culture Identification Panel was validated for nonblood
      sterile site specimens with clinical impact of rapid identification compared to
      conventional diagnostics. The panel accurately identified target organisms from
      98% of positive broth cultures a median 1.1 day faster than conventional
      techniques (P < 0.0001) with potential clinical impact in 22% of cases.

PMID- 30213467
TI  - Disseminated herpes simplex virus and varicella zoster virus co-infection in a
      patient with idiopathic thrombocytopenic purpura.
AB  - Concomitant disseminated herpes simplex virus (HSV) and varicella zoster virus
      (VZV) infection is a rare event. We describe a case of disseminated HSV and VZV
      infection in an 80-year-old patient many years after splenectomy for idiopathic
      thrombocytopenic purpura (ITP). This is the first case of disseminated HSV-1 and
      VZV infection with molecular evidence of the simultaneous presence of both
      viruses in two different body sites (the skin and cerebrospinal fluid). This adds
      to the three reports of patients developing cutaneous disseminated herpes zoster
      multiple years after splenectomy for ITP.

PMID- 30213468
TI  - A review on current trends in the treatment of human infection with H7N9-avian
      influenza A.
AB  - The H7N9 subtype of avian influenza is an enzootic and airborne virus which
      caused an influenza outbreak in China. Infected individuals mostly worked with
      poultry, suggesting H7N9 virus-infected poultry as the primary source of human
      infection. Significantly increased levels of proinflammatory mediators
      (chemokines, cytokines) during virus infection could hamper the immune system and
      aggravate the infection. Severe cases are marked by fulminant pneumonia, acute
      respiratory distress syndrome (ARDS) and encephalopathy. Left untreated, the
      condition may rapidly progress to multi-organ failure and death. Reverse
      transcription polymerase chain reaction (rRT-PCR) is the gold standard diagnostic
      test for H7N9 avian influenza. Use of neurominidase inhibitor antivirals remain
      the main treatment. New antivirals are developed to counteract neurominidase
      inhibitor resistance H7N9 viral strains. Corticosteroid use in viral pneumonia
      may provoke mortality and longer viral shedding time. Subjects at high risk of
      contracting avian influenza H7N9 infection are recommended to receive annual
      seasonal influenza vaccination.

PMID- 30213469
TI  - Infections in children with simple obesity: The relation to phagocytic function
      and serum leptin.
AB  - INTRODUCTION: There is a possible association between obesity and infections. We
      sought to investigate phagocytic functions in obese children and their relation
      to serum leptin levels. METHODS: A cross sectional, controlled study was
      conducted, comprising 40 cases with simple visceral-type obesity. Subjects were
      evaluated for percentage of caloric intake, frequency and type of infections,
      body mass index (BMI) z score, in addition to complete blood counting, serum
      leptin assay (ELISA) and Dihydrorhodamine (DHR) flowcytometry. RESULTS: Cases
      were 21 males (52.5%) and 19 females (47.5%) with mean age 7.14 years+/-2.73 SD
      with median duration of obesity 4.2 years (IQR: 2-6). Cases had higher frequency
      of infections compared with controls (p<0.001). Serum leptin was significantly
      higher among cases (t=-12.391, p<0.001), while DHR results were comparable in the
      studied groups (p=0.067). Among cases, absolute lymphocytic count (ALC)
      correlated negatively with percentage of total caloric intake (p=0.045). Leptin
      levels correlated positively with frequency of infections (p=0.019) but
      negatively with ALC (p=0.043). DHR results showed weak negative correlations with
      serum leptin (p=0.177) and with BMI Z score (p=0.109). CONCLUSION: Obese children
      are posed at increased risk of infections and have higher serum leptin levels
      with possible negative effects of leptin on phagocytic functions.

PMID- 30213470
TI  - [Acute pulmonary embolism in the emergency department: What do the guidelines
      say?]
AB  - The therapeutic strategy of acute pulmonary embolism (PE) is based on risk
      stratification of early mortality in the emergency department. Anticoagulant
      therapy should be given to all PE patients as early as possible, and direct oral
      anticoagulants are expected to replace vitamin K antagonists in the majority of
      cases. The use of a reperfusion strategy should always be considered in patients
      with high-risk PE defined as PE with clinical hemodynamic instability. Surgical
      or percutaneous embolectomy is an alternative in case of contraindication to
      thrombolytic therapy in these patients. Intermediate-risk PEs defined by a sPESI
      score of>=1 warrant hospitalization, and continuous care monitoring for patients
      presenting with elevated biomarkers and right ventricular dysfunction. Low risk
      PEs (sPESI=0) could be managed on an outpatient basis, provided that a care
      pathway had been defined beforehand.

PMID- 30213471
TI  - [What is the risk of Takotsubo in women?]
AB  - Takotsubo cardiomyopathy preferentially affects postmenopausal women (# 90%).
      Takotsubo cardiomyopathy mimics an acute coronary syndrome and is defined as a
      transient left ventricular systolic dysfunction. Diagnosis is based on the
      criteria of the Mayo Clinic. Stress is found in around 80% of cases: physical
      stress, emotional stress, medical stress. Physical stress is less found in women.
      Incidence of Takotsubo cardiomyopathy is 54.9/1,000,000 inhabitants in women
      versus only 3.6/1,000,000 inhabitants in men. Diagnosis is based on
      electrocardiogram, biomarkers, echocardiography, coronary angiography and left
      ventricular angiography, and cardiac magnetic imaging. The complete recovery of
      left ventricular systolic function must be assessed, allowing to confirm the
      diagnosis of Takotsubo cardiomyopathy.

PMID- 30213472
TI  - Factors associated with the development of avascular necrosis of the femoral head
      after non-displaced femoral neck fracture treated with internal fixation.
AB  - OBJECTIVE: To identify the factors with influence on the development of avascular
      necrosis of the femoral head (ANFH) in patients with non-displaced femoral neck
      fractures treated with internal fixation. MATERIAL AND METHOD: Retrospective
      study of cases and controls. We included non-displaced femoral neck fractures
      treated with internal fixation, and that presented ANFH with a postoperative
      follow-up of at least 2 years. The baseline variables, active comorbidities of
      the patients, the time for surgery and the number of screws used for
      osteosynthesis were recorded. Comparisons were made between the groups, those
      that presented ANFH and those that did not. By area under the curve, the cut-offs
      of age and time for surgery were located. RESULTS: An association between sex,
      active comorbidities and number of screws used and the development of ANFH was
      not observed. The cut-off points for age and time for surgery were<=69 years
      and<=43hours, respectively. No significant correlation was observed for the cut
      off time for surgery. In the multivariate analysis, age<=69 years was a
      significant predictor of the development of ANFH (OR 4.6; 95% CI 1.1 to 17.9;
      P=.028). CONCLUSIONS: The patients aged 69 years or younger were at increased
      risk of developing ANFH after undisplaced femoral neck fracture treated with
      percutaneous screws.

PMID- 30213473
TI  - The effect of portable HEPA filter air cleaner use during pregnancy on fetal
      growth: The UGAAR randomized controlled trial.
AB  - BACKGROUND: Fine particulate matter (PM2.5) exposure may impair fetal growth.
      AIMS/OBJECTIVES: Our aim was to assess the effect of portable high efficiency
      particulate air (HEPA) filter air cleaner use during pregnancy on fetal growth.
      METHODS: The Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study is a
      single-blind randomized controlled trial conducted in Ulaanbaatar, Mongolia. Non
      smoking pregnant women recruited at <=18 weeks gestation were randomized to an
      intervention (1-2 air cleaners in homes from early pregnancy until childbirth) or
      control (no air cleaners) group. Participants were not blinded to their
      intervention status. Demographic, health, and birth outcome data were obtained
      via questionnaires and clinic records. We used unadjusted linear and logistic
      regression and time-to-event analysis to evaluate the intervention. Our primary
      outcome was birth weight. Secondary outcomes were gestational age-adjusted birth
      weight, birth length, head circumference, gestational age at birth, and small for
      gestational age. The study is registered at ClinicalTrials.gov (NCT01741051).
      RESULTS: We recruited 540 participants (272 control and 268 intervention) from
      January 9, 2014 to May 1, 2015. There were 465 live births and 28 losses to
      follow up. We previously reported a 29% (95% CI: 21, 37%) reduction in indoor
      PM2.5 concentrations with portable HEPA filter air cleaner use. The median (25th,
      75th percentile) birth weights for control and intervention participants were
      3450 g (3150, 3800 g) and 3550 g (3200, 3800 g), respectively (p = 0.34). The
      intervention was not associated with birth weight (18 g; 95% CI: -84, 120 g), but
      in a pre-specified subgroup analysis of 429 term births the intervention was
      associated with an 85 g (95% CI: 3, 167 g) increase in mean birth weight.
      CONCLUSIONS: HEPA filter air cleaner use in a high pollution setting was
      associated with greater birth weight only among babies born at term.

PMID- 30213474
TI  - Apolipoprotein E in Cardiovascular Diseases: Novel Aspects of an Old-fashioned
      Enigma.
AB  - The presence of different APOE isoforms represents a well-known risk factor for
      cardiovascular diseases. Besides the pleiotropic effects of APOE polymorphism on
      heart and neurological diseases, this review summarizes the less-known functions
      of APOE and the possible implications for cardiovascular disorders. Beyond the
      role as lipid transporting protein, its involvement in lipid membrane homeostasis
      and signaling, as well as its nuclear transcriptional effects suggests a more
      complex role of APOE, receiving great interest from researchers and physicians
      from all medical fields. Due to the presence of different APOE isoforms in human
      population, understanding APOE's role in pathological processes represents not
      only a challenge, but a demand for further development of therapeutic strategies
      for cardiovascular diseases.

PMID- 30213475
TI  - Diagnostic accuracy of prehospital electrocardiograms interpreted remotely by
      emergency physicians in myocardial infarction patients.
AB  - BACKGROUND: Prehospital 12-lead electrocardiogram (ECG) is the most widely used
      screening tool for recognition of ST-segment elevation myocardial infarction
      (STEMI). However, prehospital diagnosis of STEMI based solely on ECGs can be
      challenging. OBJECTIVES: To evaluate the ability of emergency department (ED)
      physicians to accurately interpret prehospital 12-lead ECGs from a remote
      location. METHODS: All suspected prehospital STEMI patients who were transported
      by EMS and underwent angiography between 2006 and 2014 were included. We reviewed
      prehospital ECGs and grouped them based on: 1) presence or absence of a culprit
      artery lesion following angiography; and 2) whether they met the 3rd Universal
      Definition of Myocardial Infarction. We also described characteristics of ECGs
      that were misinterpreted by ED physicians. RESULTS: A total of 625 suspected
      STEMI cases were reviewed. Following angiography, 94% (590/625) of patients were
      found having a culprit artery lesion, while 6% (35/625) did not. Among these 35
      patients, 24 had ECGs that mimicked STEMI criteria and 9 had non-ischemic signs.
      Upon ECG reinterpretation, 92% (577/625) had standard STEMI criteria while 8%
      (48/625) did not. Among these 48 patients, 35 had ischemic signs ECGs and 13 did
      not. Characteristics of misinterpreted ECGs included pericarditis, early
      repolarization, STE > 1 mm (1-lead only), and negative T-wave. CONCLUSIONS:
      Remote interpretation of prehospital 12-lead ECGs by ED physicians was a useful
      diagnostic tool in this EMS system. Even if the rate of ECG misinterpretation is
      low, there is still room for ED physicians operating from a remote location to
      improve their ability to accurately diagnose STEMI patients.

PMID- 30213476
TI  - Predictive performance of the SOFA and mSOFA scoring systems for predicting in
      hospital mortality in the emergency department.
AB  - BACKGROUND: The Sequential Organ Failure Assessment (SOFA) and modified SOFA
      (mSOFA) are risk stratification systems which incorporate respiratory,
      coagulatory, liver, cardiovascular, renal, and neurologic systems to quantify the
      overall severity of acute disorder in the intensive care unit. OBJECTIVE: To
      evaluate the prognostic performance of the SOFA and mSOFA scores at arrival for
      predicting in-hospital mortality in the emergency department (ED). METHODS: All
      adult patients with an Emergency Severity Index (ESI) of 1-3 in the ED of Imam
      Reza Hospital, northeast of Iran were included from March 2016 to March 2017. The
      predictive performance of the SOFA or mSOFA scores were expressed in terms of
      accuracy (Brier Score, BS and Brier Skill Score, BSS), discrimination (Area Under
      the Receiver Operating Characteristic Curve, AUC), and calibration. RESULTS: A
      total of 2205 patients (mean age 61.8 +/- 18.5 years, 53% male) were included.
      The overall in-hospital mortality was 19%. For SOFA and mSOFA the BS was 0.209
      and 0.192 and the BSS was 0.11 and 0.09, respectively. The estimated AUCs of SOFA
      and mSOFA models were 0.751 and 0.739, respectively. No significant difference
      was observed between the AUCs (P = 0.186). The Hosmer-Lemeshow test did not show
      that the predictions deviated from the true probabilities. Also, the calibration
      plots revealed good agreement between the actual and predicted probabilities.
      CONCLUSION: The SOFA and mSOFA scores demonstrated fair discrimination and good
      calibration in predicting in-hospital mortality when applied to ED. However,
      further external validation studies are needed before their use in routine
      clinical care.

PMID- 30213477
TI  - Fetal-placental crosstalk occurs through fetal cytokine synthesis and placental
      clearance.
AB  - BACKGROUND: Cytokines modulate fetal well-being and contribute to parturition.
      Their origin in fetal blood, whether maternal, placental or fetal, at the time of
      parturition remains unclear. OBJECTIVE: To determine fetal and placental
      contributions to circulating fetal cytokines by measuring umbilical arterial
      (UmA) and venous (UmV) concentration differences in uncomplicated term
      pregnancies in the absence and presence of labor. METHODS: Term uncomplicated
      pregnancies were assessed: Group 1 were not in labor and delivered by elective
      cesarean section (n = 20); Group 2 delivered vaginally following uncomplicated
      pregnancy and labor (n = 30). UmA and UmV blood was collected before delivery of
      the placenta to measure circulating cytokines. Placental tissue was collected for
      histology and to determine cytokine contents and localization. RESULTS: Group 1
      UmA and UmV IL-10 concentrations were similar (504 +/- 15 and 468 +/- 16 pg/ml,
      respectively; P >= 0.1); other cytokines were below level of detection. During
      labor, IL-10 concentrations increased 15-34%, but placental contents decreased.
      Group 2 UmA IL-6 and IL-8 concentrations increased (P < 0.001) to 16.7 +/- 1.6
      and 18.4 +/- 4.3 pg/ml, respectively, but were less (P < 0.001) in UmV, 0.29 +/-
      0.2 and 0.74 +/- 0.3 pg/ml, respectively, demonstrating placental clearances
      >=97%. This was associated with >6-fold increases in placental IL-6/IL-8 contents
      (P < 0.001) and chorioamniotic infiltration of activated maternal neutrophils. IL
      6 and IL-10 were localized to villous syncytiotrophoblasts. CONCLUSIONS: In
      uncomplicated term pregnancies fetal circulating IL-10 is likely of placental
      origin, whereas IL-6/IL-8 are derived from the fetus, increase during
      parturition, and circulating levels are modulated by non-saturable placental
      clearance, revealing a novel pathway for fetal-placental crosstalk and signaling.

PMID- 30213478
TI  - Race and risk of maternal vascular malperfusion lesions in the placenta.
AB  - INTRODUCTION: The biological mechanisms that underlie racial disparities in
      placenta-mediated pregnancy complications remain unknown. Placental evidence of
      maternal vascular malperfusion (MVM), a common pathologic feature of these
      outcomes, represents hypoxic-ischemic damage to the placenta. We sought to
      separately estimate the risk of MVM and individual lesions associated with
      maternal race. METHODS: This was a retrospective cohort study of black and white
      women with singleton live births and placental pathology data at Magee-Womens
      Hospital during 2008-2012 (n = 15,581). MVM consisted of >=1 individual lesions:
      low placental weight, decidual vasculopathy, accelerated villous maturation,
      infarcts, and fibrinoid deposition. We separately compared the incidence of MVM
      and individual lesions in black and white women using logistic regression with
      generalized estimating equations. RESULTS: After adjusting for covariates, black
      women had increased risks of MVM (aOR 1.14, 95% CI 1.05-1.23), low placental
      weight (aOR 1.41, 95% CI 1.28-1.55), and decidual vasculopathy (aOR 1.58, 95% CI
      1.36-1.83), also observed in uncomplicated, preterm, and term births. Conversely,
      black women had decreased risk of infarcts (aOR 0.84, 95% CI 0.75-0.95) compared
      with white women, also observed in uncomplicated and full-term births. Race was
      not associated with accelerated villous maturation or fibrinoid deposition.
      Inverse probability weighting to account for potential selection bias generated
      similar results. DISCUSSION: Our findings suggest that excess risks of MVM,
      specifically low placental weight and decidual vasculopathy in black women may be
      due to a pathological susceptibility to an underlying high-risk vascular
      phenotype. The clinical significance of race differences in the occurrence of
      infarcts warrants further investigation.

PMID- 30213479
TI  - Evaluating maternal hyperglycemic exposure and fetal placental arterial
      dysfunction in a dual cotyledon, dual perfusion model.
AB  - BACKGROUND: Gestational diabetes affects almost 1 in 10 pregnancies and is
      associated with adverse outcomes including fetal demise. Pregnancy complications
      related to diabetes are attributed to placental vascular dysfunction. With
      diabetes, maternal hyperglycemia is thought to promote placental
      vasoconstriction. However, it remains poorly understood if and how hyperglycemia
      leads to placental vascular dysfunction or if humoral factors related to maternal
      diabetes are responsible. METHODS AND RESULTS: Utilizing a human placenta dual
      cotyledon, dual perfusion assay we examined the arterial pressure response to the
      thromboxane mimetic U44619, in cotyledons exposed to normal vs. a hyperglycemic
      infusion into the intervillous space. Tissues were then analyzed for the activity
      of key signaling molecules related to vascular tone; eNOS, Akt, PKA and VEGFR2.
      Results indicate a significant increase in fetal vascular resistance with
      maternal exposure to hyperglycemia. This response corresponded with a reduction
      in the phosphorylation of eNOS at Ser1177 and Akt at Thr308. In contrast, VEGFR2
      at Tyr1175 and PKA at Thr197 were not different with hyperglycemia. CONCLUSION:
      Reductions of eNOS and Akt phosphorylation at key residues implicated in nitric
      oxide production suggest that hyperglycemia alters the vasodilatory signaling of
      placental vessels. In contrast, acute hyperglycemic exposure may not alter
      vasoconstriction via VEGF and PKA signaling. Altogether our results link
      hyperglycemic exposure in human placentas to nitric oxide signaling; a mechanisms
      that may account for the elevations in vascular resistance commonly observed in
      diabetic pregnancies.

PMID- 30213480
TI  - Postpartum placental CT angiography in normal pregnancies and in those
      complicated by diabetes mellitus.
AB  - INTRODUCTION: Pregnancy complicated by diabetes mellitus (DM) is a central
      obstetric problem often complicated by fetal macrosomia and increased risk of
      intrapartum asphyxia. This risk might be explained by fetoplacental vascular
      abnormalities. This study aimed to investigate the fetoplacental vascular volume
      by placental CT angiography in normal pregnancies and in pregnancies complicated
      by type 1 DM (T1DM), diet controlled gestational DM (GDMd), and insulin treated
      gestational DM (GDMi). METHODS: Postpartum, barium contrast enhanced placental CT
      angiography was performed in 27 normal pregnancies and 25 DM pregnancies (8 T1DM,
      8 GDMd, and 9 GDMi). The fetoplacental vascular volume/placenta weight (FVV/PW)
      ratio and fetoplacental vascular volume/birth weight (FVV/BW)-ratio of each
      diabetic group were compared to the normal group with multiple regression
      analysis adjusted for GA. In all pregnancies a standardized histopathological
      placental examination was performed postpartum. RESULTS: In normal pregnancies,
      the fetoplacental vascular volume increased with GA (p < 0.001), placental weight
      (p < 0.001), and birth weight (p < 0.001). In T1DM and GDMi pregnancies, the
      gestational age adjusted placental weight and the birth weight were increased
      when compared to normal pregnancies (p < 0.05). The FVV/BW-ratio was
      significantly reduced in both T1DM and GDMi pregnancies when compared to normal
      pregnancies (p = 0.003 and p = 0.009, respectively). DISCUSSION: This study
      demonstrates, that in insulin treated DM pregnancies the fetus as well as the
      placenta is larger than normal. However, despite a large placenta, a relatively
      smaller fetoplacental vascular volume supplies the macrosomic fetus. This finding
      might explain why fetuses from insulin treated DM pregnancies have high
      vulnerability to intrauterine and intrapartum asphyxia.

PMID- 30213481
TI  - Decreased apparent diffusion coefficient in the placentas of monochorionic twins
      with selective intrauterine growth restriction.
AB  - OBJECTIVES: The apparent diffusion coefficient (ADC) was associated with the
      onset of intrauterine growth restriction in singleton pregnancies. However, the
      correlation of ADC with selective intrauterine growth restriction (sIUGR) of
      monochorionic (MC) twin pregnancies remained unknown. In this study, we aimed to
      evaluate the association of ADC with sIUGR in MC twin pregnancies by exploring
      diffusion weighted MR imaging (DWI). METHODS: Fifty-one MC twin pregnancies,
      consisting 19 cases of sIUGR and 32 cases without sIUGR, were re-analyzed by DWI.
      ADCs were quantitated from two regions of interest, surrounding the insertion of
      the umbilical cord of placenta for each twin. A rADC (ADClarger twin/ADCsmaller
      twin) in each placenta was also evaluated. Then ADCs and rADCs were compared
      between cases with and without sIUGR. RESULTS: The ADC in cases with sIUGR was
      significantly decreased compared with cases without sIUGR (1.846 * 103 vs 2.471 *
      103 mm2/s, p < 0.001). The rADC in cases with sIUGR was significantly increased
      (1.346 vs 1.053, p < 0.001). CONCLUSIONS: The ADC decreases and the rADC
      increases in the placentas of MC twins with sIUGR, suggesting that diffusion in
      the placenta is restricted in pregnancies with sIUGR.

PMID- 30213482
TI  - Regulation of human placental drug transporters in HCV infection and their
      influence on direct acting antiviral medications.
AB  - INTRODUCTION: The objectives of this study were to determine how HCV infection
      affects placental drug transporters, and to determine the role of drug
      transporters on the cellular accumulation of direct-acting antiviral drugs in
      human trophoblasts. METHODS: Eighty-four ABC and SLC transporter genes were first
      screened in normal and HCV infected pregnant women using PCR profiler array. The
      changes in expression were confirmed by qPCR and Western blot. The impact of
      selected drug transporters on the cellular accumulation of radiolabeled antiviral
      drugs sofosbuvir, entecavir, and tenofovir was measured in primary human
      trophoblasts (PHT) and BeWo b30 cells in the presence or absence of transporter
      specific inhibitors. PHT were then treated with CL097, ssRNA40, and imquimod to
      determine the impact of Toll-like receptor (TLR) 7/8 activation on drug
      transporter expression. RESULTS: The expression of the ABC efflux transporters
      ABCB1/P-gp and ABCG2/BCRP was increased in placenta of women with HCV, while the
      nucleoside transporters SLC29A1/ENT1 and SLC29A2/ENT2 remained unchanged. The
      accumulation of sofosbuvir and tenofovir was unaffected by inhibition of these
      transporters in trophoblast cells. Entecavir accumulation was decreased by the
      inhibition of ENT2. P-gp and BCRP inhibition enhanced entecavir accumulation in
      BeWo b30, but not PHT. Overall, there was little effect of TLR7/8 activation on
      these drug transporters, and the accumulation of entecavir in PHT. DISCUSSION:
      The data suggest that expression of placental drug transporters and selection of
      antiviral drug may impact fetal drug exposure in pregnancies complicated by HCV
      infections.

PMID- 30213483
TI  - Abnormal steroidogenesis and aromatase activity in preeclampsia.
AB  - INTRODUCTION: Estrogens and progesterone play critical roles in angiogenesis and
      vasodilation. Moreover, placental aromatase deficiency is detected in women with
      preeclampsia (PE) at delivery. We hypothesized that abnormal steroidogenesis
      occurs much earlier than typical PE diagnosis. Thus, we investigated whether the
      circulating steroid profile was already disturbed at 24-29 weeks of gestation in
      women with subsequent PE, and compared the profile with that of women with
      "placental" small gestational age (SGA) without PE. METHODS: We selected
      nulliparous women (n = 90) from the MOMA trial, including women with PE (n = 25),
      SGA (n = 25), and controls (NP; n = 40), for plasma steroid profiling by gas
      chromatography/mass spectrometry and to measure placental growth factor and
      soluble fms-like tyrosine kinase-1. Placental aromatase expression was evaluated
      in a new set of women. RESULTS: Compared with that of controls, the women with PE
      had a significantly lower estrone/androstenedione ratio, and exhibited a
      decreasing trend for estradiol and estrone levels. Lower estriol levels were
      observed in the SGA group compared to the NP group. Compared with that of
      controls, the women with PE and SGA had significantly higher levels of 20alpha
      dihydroprogesterone (20alpha-DHP) and 20alpha-DHP/progesterone ratios.
      Pregnenolone sulfate levels were lower in the PE group than in the NP and SGA
      groups. Decreased expression of aromatase was observed in the PE group compared
      to the control group. DISCUSSION: Preeclampsia appears to be characterized by
      specific steroidogenesis dysregulation long before PE diagnosis, highlighting
      potential new biomarkers of PE.

PMID- 30213484
TI  - Impairment of trophoblast survival and differentiation by LXR ligands is
      prevented by cholesterol but not ABCA1 silencing.
AB  - INTRODUCTION: The Liver X Receptors (LXRs) drive the transcriptional response to
      excess intracellular cholesterol. Oxysterols, the products of cholesterol
      oxidation, are activating ligands for LXR that can accumulate under conditions of
      oxidative stress and disrupt cholesterol homeostasis. While activation of LXR
      inhibits trophoblast differentiation, the impact of LXR on trophoblast physiology
      or cholesterol homeostasis is incompletely understood. We sought to determine if
      the effects of LXR activation can be ameliorated through modification of
      cholesterol bioavailability or inhibition of LXR-driven cholesterol efflux in
      trophoblasts. METHODS: We measured the effect of oxysterol exposure on BeWo cells
      and primary human trophoblasts (PHT cells) cultured in lipoprotein-deficient
      medium. We also measured the effect of the synthetic, LXR-specific ligand
      T0901317 on PHT cell differentiation and survival. Finally, we silenced the ATP
      binding cassette transporter A1 (ABCA1), a transcriptional target of LXR that
      drives cholesterol efflux, to determine if inhibition of cholesterol efflux could
      block the effects of T0901317. RESULTS: Oxysterols inhibited BeWo survival and
      PHT cell differentiation, and these effects were blocked by cholesterol
      supplementation. T0901317 also inhibited PHT cell differentiation, and this
      effect was similarly blocked by cholesterol. Unlike cholesterol however, ABCA1
      silencing did not modify the effect of T0901317 on PHT cell differentiation.
      DISCUSSION: Oxysterols and LXR inhibit trophoblast survival and differentiation
      exclusively in conditions of cholesterol scarcity. These findings underscore the
      importance of cholesterol homeostasis in the maintenance of placental function
      and suggest that pathways regulating cholesterol homeostasis may represent
      therapeutic targets to mitigate harmful sequelae of placental injury.

PMID- 30213485
TI  - Asymmetric dimethylarginine levels in preeclampsia - Systematic review and meta
      analysis.
AB  - OBJECTIVE: Preeclampsia (PE) is the leading cause of maternal and perinatal
      mortality around the world. The impaired function of fetal-placental vasculature
      is a key factor in PE. Several studies have investigated the connection between
      PE and endothelial dysfunction. Also, many authors have examined the changes in
      asymmetric dimethylarginine (ADMA) as a prominent marker of endothelial
      dysfunction. Our study aim is to review and analyse the connections between PE
      and ADMA levels. METHODS: To obtain data we performed a comprehensive literature
      search in Pubmed, Embase and Web of Science. Standardized mean differences were
      used to estimate the differences in ADMA levels. RESULTS: The quantitative
      analysis included 10 studies reporting a total number of 631 PE and 498 healthy
      pregnant individuals. We found significantly higher ADMA levels in PE patients
      compared to controls, when comparing the ADMA levels of the patients to the ADMA
      levels of the controls (z = 5.93, p < 0.001). This difference was present
      regardless of the measurement method. Regarding the onset of PE, we found
      significantly higher ADMA levels in patients suffering from early-onset PE when
      comparing the ADMA levels of the early-onset PE patients to that of the controls
      (z = 2.82, p = 0.005). However, we did not find such difference when we compared
      late-onset PE patients' ADMA levels to controls. CONCLUSION: ADMA is
      significantly higher in PE patients than in the controls. Elevated ADMA levels
      can play a major role in the development of PE, but more research is needed to
      clarify the connection between the two.

PMID- 30213487
TI  - Embryonic lethality in mice due to carnitine transporter OCTN2 defect and
      placental carnitine deficiency.
AB  - l-Carnitine plays a crucial role in uptake and subsequent beta-oxidation of long
      chain fatty acids in the mitochondria. Placental trophoblast cells oxidize long
      chain fatty acids for energy production. Here we present data showing that l
      carnitine deficiency due to a defect in the carnitine transporter OCTN2 (SLC22A5)
      in a mouse model leads to embryonic lethality. Placental levels of l-carnitine
      are reduced to <10% of normal and deficiency of l-carnitine is associated with
      markedly reduced expression of several growth factors and transforming growth
      factor beta (TGF-beta) genes. This report links for the first time reduced l
      carnitine levels in the placenta to embryonic lethality.

PMID- 30213486
TI  - Differential expression of leukemia inhibitory factor and insulin like growth
      factor-1 between normal pregnancies, partial hydatidiform moles and complete
      hydatidiform moles.
AB  - INTRODUCTION: Leukemia inhibitory factor (LIF) and insulin like growth factor-1
      (IGF-1) are two of the most important growth factors mediating trophoblast
      actions. We hypothesized that the localization and expression patterns of LIF and
      IGF-1 in partial and complete hydatidiform moles (HM) compared with normal first
      trimester placentas may provide an understanding of the proliferative processes
      in HMs. METHODS: The study population included curettage material of women
      diagnosed as complete or partial HM as a result of histopathological and
      immunohistochemical examination (complete HM group, n = 8; partial HM group, n =
      8) and women undergoing dilatation&curettage for unwanted pregnancies (control
      group, n = 8). Expression of LIF and IGF-1 among placental cell groups was
      evaluated immunohistochemically and given a score depending on immunostaining
      intensity. RESULTS: In normal chorionic villi strong expression of LIF and IGF-1
      was present. Both LIF and IGF-1 expressions were weaker in the chorionic villi of
      complete HMs. In complete mole decidua there was a significant decrease in
      glandular and endothelial IGF-1 expression along with a decrease in decidual cell
      LIF expression compared to normal first trimester decidua. LIF expression in
      extravillous trophoblasts was stronger in complete molar placentas compared to
      normal placentas. DISCUSSION: LIF and IGF-1 are important regulators of
      trophoblast proliferation and invasion. Differential expression of LIF and IGF-1
      in molar trophoblasts and chorionic villi might have a role in regulation of
      trophoblasts in complete moles. Decreased expression of glandular IGF-1 and
      decidual LIF might be related to the decidual changes during trophoblastic
      proliferation and invasion of decidua in complete HMs.

PMID- 30213488
TI  - Comparative determination of placental perfusion by magnetic resonance imaging
      and contrast-enhanced ultrasound in a murine model of intrauterine growth
      restriction.
AB  - INTRODUCTION: Exploration of placental perfusion is essential in screening for
      dysfunctions impairing fetal growth. The objective of this study was to assess
      the potential value of contrast-enhanced ultrasonography (CEUS) and magnetic
      resonance imaging (MRI) for examining placental perfusion in a murine model of
      intrauterine growth restriction (IUGR). We also studied the reproducibility of
      perfusion quantification by CEUS. METHODS: Pregnant Sprague Dawley rat models of
      IUGR were studied during the third trimester. Unilateral uterine artery ligation
      induced IUGR. Placental perfusion was evaluated by CEUS and perfusion MRI with
      gadolinium for both ligated and control fetoplacental units. The kinetic
      parameters of the two imaging modalities were then compared. RESULTS: The
      analysis included 20 rats. The study showed good reproducibility of the CEUS
      indicators. The CEUS perfusion index approximated the blood flow rate and was
      halved in the ligation group (27.9 [u.a] (+/-14.8)) versus 61 [u.a] (+/-22.3) on
      the control side (P = 0.0003). MRI with gadolinium injection showed a clear
      reduction in the blood flow rate to 51.2 mL/min/100 mL (IQR 34.9-54.9) in the
      ligated horn, compared with 90.9 mL/min/100 mL (IQR 85.1-95.7) for the control
      side (P < 0.0001). The semiquantitative indicators obtained from the kinetic
      curves for both CEUS and MRI showed similar trends. Nonetheless, values were more
      widely dispersed with CEUS than MRI. DISCUSSION: The similar results for the
      quantification of placental perfusion by MRI and CEUS reinforce the likelihood
      that CEUS can be used to identify IUGR in a murine model induced by uterine
      vessel ligation.

PMID- 30213490
TI  - Dynamic glucose enhanced MRI of the placenta in a mouse model of intrauterine
      inflammation.
AB  - INTRODUCTION: We investigated the feasibility of dynamic glucose enhanced (DGE)
      MRI in accessing placental function in a mouse model of intrauterine inflammatory
      injury (IUI). DGE uses the glucose chemical exchange saturation transfer
      (glucoCEST) effect to reflect infused d-glucose. METHODS: IUI was induced in
      pregnant CD1 mice by intrauterine injection of lipopolysaccharide (LPS) on
      embryonic day 17. In vivo MRI was performed on an 11.7 T scanner at 6 h s after
      injury, and glucoCEST effect was measured using an on-resonance variable delay
      multi-pulse (onVDMP) technique. onVDMP acquisition was repeated over a period of
      25 min, and d-glucose was infused 5 min after the start. The time-resolved
      glucoCEST signals were characterized using the normalized signal difference
      (DeltaSN) between onVDMP-labeled and nonlabeled images. RESULTS: DeltaSN in the
      PBS-exposed placentae (n = 6) showed an initial drop between 1 and 3 min after
      infusion, followed by a positive peak between 5 and 20 min, the time period
      expected to be associated with the process of glucose uptake and transport. In
      the LPS-exposed placentae (n = 10), the positive peak was reduced or even absent,
      and the corresponding area-under-the-curve (AUC) was significantly lower than
      that in the controls. Particularly, the AUC maps suggested prominent group
      differences in the fetal side of the placenta. We also found that glucose
      transporter 1 in the LPS-exposed placentae did not respond to maternal glucose
      challenge. DISCUSSION: DGE-MRI is useful for evaluating placental functions
      related to glucose utilization. The technique uses a non-toxic biodegradable
      agent (d-glucose) and thus has a potential for rapid translation to human studies
      of placental disorders.

PMID- 30213489
TI  - Comparison of diameter-based and image-based measures of surface area from gross
      placental pathology for use in epidemiologic studies.
AB  - Placental surface area is often estimated using diameter measurements. However,
      as many placentas are not elliptical, we were interested in the validity of these
      estimates. We compared placental surface area from images for 491 singletons from
      the Stillbirth Collaborative Research Network (SCRN) Study (416 live births, 75
      stillbirths) to estimates obtained using diameter measurements. Placental images
      and diameters were obtained from pathologic assessments conducted for the SCRN
      Study and images were analyzed using ImageJ software. On average, diameter-based
      measures underestimated surface area by -5.58% (95% confidence interval: -30.23,
      19.07); results were consistent for normal and abnormal shapes. The association
      between surface area and birthweight was similar for both measures. Thus,
      diameter-based surface area can be used to estimate placental surface area.

PMID- 30213491
TI  - Sex-specific and lasting effects of a single course of antenatal betamethasone
      treatment on human placental 11beta-HSD2.
AB  - INTRODUCTION: We have previously shown that even a single course of antenatal
      betamethasone (BET) as an inductor for lung maturity reduces birth weight and
      head circumference. Moreover, animal studies link BET administration to
      alterations of the hypothalamic-pituitary-adrenal-gland-axis (HPA). The
      unhindered development of the fetal HPA axis is dependent on the function and
      activity of 11beta-hydroxysteroiddehydrogenase type 2 (11beta-HSD2), a
      transplacental cortisol barrier. Therefore, we investigated the effects of BET on
      this transplacental barrier and fetal growth. METHODS: Pregnant women treated
      with a single course of BET between 23 + 5 to 34 + 0 weeks of gestation were
      compared to gestational-age-matched controls. Placental size and neonatal
      anthropometrics were taken. Cortisol and ACTH levels were measured in maternal
      and umbilical cord blood samples. Placental 11beta-hydroxysteroiddehydrogenase
      type 1 (11beta-HSD1) protein levels and 11beta-HSD2 protein and activity levels
      were determined. Parameters were analyzed independent of sex, and in subgroups
      divided by gender and gestational age. RESULTS: In term born females, BET
      administration was associated with reduced head circumference and decreased
      11beta-HSD2 protein levels and enzyme activity. Males treated with BET,
      especially those born prematurely, showed increased 11beta-HSD2 protein levels.
      CONCLUSION: A single course of BET alters placental glucocorticoid metabolism in
      a sex-specific manner. Decreased 11beta-HSD2 levels in term born females may lead
      to an increased placental transfer of maternal cortisol and therefore result in a
      reduced head circumference and a higher risk for altered stress response in
      adulthood. Further research is needed to conclude the significance of increased
      11beta-HSD2 levels in males.

PMID- 30213492
TI  - Macrophage- but not monocyte-derived extracellular vesicles induce placental pro
      inflammatory responses.
AB  - The placenta sheds extracellular vesicles (EVs), including exosomes, into the
      maternal circulation. We recently demonstrated that this trafficking of EVs is bi
      directional; with uptake of macrophage exosomes by the placenta inducing cytokine
      release. The specificity of this response is currently unknown. THP-1 cells were
      cultured as monocytes or differentiated to macrophages, and EVs isolated by ultra
      centrifugation. The effect of EVs on human placental explants was measured by
      cytokine ELISA/luminex. Macrophage, but not monocyte, EVs induce the release of
      pro-inflammatory cytokines by the placenta. Thus, placental responses to immune
      cell EVs, including exosomes, reflects the phenotype of the source cell.

PMID- 30213494
TI  - Bisphenol A induced oxidative stress mediated genotoxicity in Drosophila
      melanogaster.
AB  - This study investigates Bisphenol A (BPA) induced oxidative stress that mediates
      the genotoxicity in in vivo model Drosophila melanogaster. The calculated LC50
      for BPA was 12.35 MUg/mL. The strains of D. melanogaster were reared in 0.1, 1.0,
      2.5 and 5.0 MUg/mL BPA treated food media from the embryonic stage (egg);
      oxidative stress and genotoxicity parameters were analyzed. Food intake analysis
      confirmed that BPA is not an anti feedant for Drosophila larvae and it consumed
      BPA containing food. Increased reactive oxygen species (ROS) and lipid
      peroxidation (LPO) and depletion of superoxide dismutase (SOD), catalase (CAT),
      glutathione (GSH) and glutathione-s-transferase (GST) antioxidant activities were
      observed in BPA treated groups compared to control. Positive single spots/wing
      frequencies were observed in standard (ST) and high bioactivation (HB) crosses of
      marker heterozygous (MH; mwh/flr3) and balancer heterozygous (BH; mwh/TM3)
      genotype flies indicating BPA is mutagenic and not recombinogenic. A significant
      increase in tail length and % tail DNA in Comet assay after BPA treatment reveals
      that BPA has a potential to induce the genotoxicity. Present study suggests that
      BPA exposure induces oxidative stress, which could be one of the possible
      mechanisms for induction of genotoxicity.

PMID- 30213493
TI  - Maternal obesity is not associated with placental lipid accumulation in women
      with high omega-3 fatty acid levels.
AB  - INTRODUCTION: Placentas of obese women have higher lipid content compared to lean
      women. We have previously shown that supplementation of overweight and obese
      women with omega-3 fatty acids decreases placental esterification pathways and
      total lipid content in a mid-western population (Ohio). We hypothesized that
      placental lipid accumulation and inflammation would be similar between lean and
      obese women living in a region of high omega-3 intake, such as Hawaii. METHODS:
      Fifty-five healthy, normal glucose tolerant women from Honolulu Hawaii,
      dichotomized based on pre-pregnancy BMI into lean (BMI <25 kg/m2, n = 29) and
      obese (BMI >30 kg/m2, n = 26), were recruited at scheduled term cesarean
      delivery. Maternal plasma DHA levels were analyzed by mass spectrometry.
      Expression of key genes involved in fatty acid oxidation and esterification were
      measured in placental tissue using qPCR. Total lipids were extracted from
      placental tissue via the Folch method. TNF-alpha concentration was measured by
      enzyme-linked immunosorbent assay in placental lysates. RESULTS: DHA levels were
      higher in lean women compared to obese women (P = 0.02). However, DHA levels in
      obese women in Hawaii were eight times higher compared to obese Ohioan women
      (P=<0.0001). Placental lipid content and expression of key genes involved in
      fatty acid oxidation and esterification were similar (P > 0.05) between lean and
      obese women in Hawaii. Furthermore, TNF-alpha placental lysates were not
      different between lean and obese women. CONCLUSIONS: Though obese women in Hawaii
      have lower DHA levels compared to their lean counterparts, these levels remain
      over eight times as high as obese Ohioan women. These relatively high plasma
      omega-3 levels in obese women in Hawaii may suppress placental lipid
      esterification/storage and inflammation to the same levels of lean women, as seen
      previously in vitro.

PMID- 30213496
TI  - Corrigendum to "Maduramicin-activated protein phosphatase 2A results in
      extracellular signal-regulated kinase 1/2 inhibition, leading to cytotoxicity in
      myocardial H9c2 cells" [Toxicol. Lett. 284 (2018) 96-102].

PMID- 30213495
TI  - One-year survival after in-hospital cardiac arrest: A systematic review and meta
      analysis.
AB  - INTRODUCTION: In-hospital cardiac arrest is a major adverse event with an
      incidence of 1-6/1000 admissions. It has been poorly researched and data on
      survival is limited. The outcome of interest in IHCA research is predominantly
      survival to discharge, however recent guidelines warrant for more long-term
      outcomes. In this systematic review we sought to quantitatively summarize one
      year survival after in-hospital cardiac arrest. METHODS: For this systematic
      review and meta-analysis we performed a systematic search of all published data
      on one-year survival after IHCA up to March 9th, 2018. Results of the meta
      analyses are presented as pooled proportions with corresponding 95% prediction
      intervals (95%PI). Between-study heterogeneity was assessed using I2 statistic
      and the DerSimonian-Laird estimator for tau2. Subgroup analyses were performed
      for cardiac and non-cardiac patients. RESULTS: We included 40 studies in our
      systematic review and meta-analysis. The pooled one-year survival after in
      hospital cardiac arrest was 13.4% (95%PI: 5.6-28.8%, I2 = 100%). Subgroup
      analysis of cardiac patients revealed a one-year survival of 39.3% (16.1%-68.6%)
      in patients with a non-cardiac admission characteristic one-year survival was
      10.7% (4.4%-23.6%). These data cover the period 1985-2018 and show a modest
      change in survival over that period (10-year OR: 1.70, 95% CI: 1.04-2.76).
      DISCUSSION: One-year survival after in-hospital cardiac arrest is poor. Survival
      is higher in patients admitted to cardiac wards. The time trend between 1985-2018
      has shown a modest improvement in one-year survival rates. Research into IHCA
      population characteristics might elicit the issue of heterogeneity and stagnated
      survival over the past decades.

PMID- 30213497
TI  - Zaprinast diminished pain and enhanced opioid analgesia in a rat neuropathic pain
      model.
AB  - The mechanism of neuropathic pain is complex and unclear. Based on our results,
      we postulate that an intensification of the kynurenine pathway occurs as a
      consequence of nerve injury. The G protein-coupled receptor 35 (GPR35) is
      important for kynurenine pathway activation. Cyclic GMP-specific
      phosphodiesterase inhibitors have also been shown to have beneficial effects on
      neuropathic pain. Therefore, the aims of our research were to elucidate how a
      substance that acts as both an agonist of GPR35 and an inhibitor of
      phosphodiesterase influences neuropathic pain in a rat model. Here, we
      demonstrated that preemptive and repeated intrathecal (i.t.) administration (16 h
      and 1 h before injury and then after nerve ligation daily for 7 days) of
      zaprinast (1 MUg/5 MUl) significantly attenuated mechanical (von Frey test) and
      thermal (cold plate test) hypersensitivity measured on day 7 after chronic
      constriction injury, and the effect of even a single injection lasted up to 24 h.
      Our data indicate that zaprinast diminished the number of IBA1-positive cells and
      consequently attenuated the levels of IL-1beta, IL-6, IL-18, and NOS2 in the
      lumbar spinal cord and/or dorsal root ganglia. Our results also demonstrated that
      zaprinast potentiated the analgesic properties of morphine and buprenorphine. In
      summary, in a neuropathic pain model, zaprinast significantly reduced pain
      symptoms and enhanced the effectiveness of opioids. Our data provide new evidence
      that modulation of both GPR35 and phosphodiesterase could be an important
      strategy for innovative pharmacological treatments designed to decrease
      hypersensitivity evoked by nerve injury.

PMID- 30213498
TI  - Inhibition of pyruvate dehydrogenase kinase 1 enhances the anti-cancer effect of
      EGFR tyrosine kinase inhibitors in non-small cell lung cancer.
AB  - Although epidermal growth factor receptor (EGFR) inhibitors have been used to
      treat non-small cell lung cancer (NSCLC) for decades with great success in
      patients with EGFR mutations, acquired-resistance inevitably occurs after long
      term exposure to the treatment of EGFR inhibitors. Glycolysis is a predominant
      process for most cancer cells to utilize glucose, which referred to as the
      Warburg Effect. Targeting critical enzymes, such as pyruvate dehydrogenase kinase
      1 (PDK1) that inversely regulating the process of glycolysis could be a promising
      approach to work alone or in combination with other treatments for cancer
      therapy. The purpose of this study is to evaluate whether PDK1 inhibition could
      enhance the anti-cancer effects of EGFR-TKi. Herein, we utilized a recently
      reported PDK1 inhibitor 2,2-Dichloro-1-(4-isopropoxy-3-nitrophenyl)ethan-1-one
      (Cpd64), which was more potent and selective than dichloroacetate (DCA) and/or
      dichloroacetophenone (DAP), to study the mechanism of PDK1 inhibition in TKi
      mediated anti-cancer activity. We found that the introduction of Cpd64 in EGFR
      TKi therapy enhanced the anti-proliferative effects in EGFR-mutant NSCLC cells
      under hypoxia. In particular, Cpd64 was shown to increase the activity of
      pyruvate dehydrogenase (PDH) and improved XPHOS, such as elevated mitochondrial
      respiration, and increased ATP generation, which effectively modulated the
      upregulation of PDK1 by EGFR-TKi treatment. We have observed that Cpd64
      effectively enhanced the tumor growth inhibition induced by erlotinib in a NCI
      H1975 xenograft mouse model. Collectively, our results suggested that combined
      use of selective PDK inhibitor and EGFR-TKi could be a potential strategy for
      NSCLC therapy.

PMID- 30213499
TI  - Canonical and Non-Canonical Wnt Signaling in Immune Cells.
AB  - Cell differentiation, proliferation, and death are vital for immune homeostasis.
      Wnt signaling plays essential roles in processes across species. The roles of Wnt
      signaling proteins and Wnt ligands have been studied in the past, but the context
      dependent mechanisms and functions of these pathways in immune responses remain
      unclear. Recent findings regarding the role of Wnt ligands and Wnt signaling in
      immune cells and their immunomodulatory mechanisms suggest that Wnt ligands and
      signaling are significant in regulating immune responses. We introduce recent key
      findings and future perspectives on Wnt ligands and their signaling pathways in
      immune cells as well as the immunological roles and functions of Wnt antagonists.

PMID- 30213500
TI  - Paragonimus westermani infection manifesting as a pulmonary cavity and adrenal
      gland mass: A case report.
AB  - We report a case of Paragonimus westermani infection simultaneously affecting two
      separate organs that presented as both a pulmonary cavity and adrenal mass in an
      immunocompromised host. A 65-year-old male with a previous kidney transplant
      visited our clinic because of hemoptysis. Chest computed tomography (CT) showed a
      pulmonary cavity and right adrenal gland mass. The Aspergillus antigen titer in
      bronchial lavage fluid was elevated and showed positive conversion. It was
      necessary to differentiate lung cancer with adrenal gland metastasis from a
      fungal infection with an adrenal gland adenoma. Positron emission tomography CT
      suggested benign disease, and it was misdiagnosed as pulmonary aspergillosis
      based on the elevated Aspergillus antigen titer in the bronchial lavage fluid.
      Owing to the adverse effects of anti-fungal treatment, the patient underwent
      wedge resection of the lung and P. westermani was confirmed. A careful history
      revealed that the patient had eaten raw freshwater crabs 3 years earlier, and a
      test for serum antibodies to P. westermani was positive. Despite treatment with
      praziquantel, the adrenal mass persisted on 3-month follow-up CT. A right
      adrenalectomy was performed and a P. westermani infection was confirmed.

PMID- 30213501
TI  - On the subject of writing letters of recommendation.

PMID- 30213502
TI  - Texting as a Strategy to Increase Contraception Use Compliance in Adolescent
      Females.

PMID- 30213503
TI  - Cross-species molecular dissection across alcohol behavioral domains.
AB  - This review summarizes the proceedings of a symposium presented at the
      "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference
      held in Volterra, Italy on May 9-12, 2017. Psychiatric diseases, including
      alcohol-use disorders (AUDs), are influenced through complex interactions of
      genes, neurobiological pathways, and environmental influences. A better
      understanding of the common neurobiological mechanisms underlying an AUD
      necessitates an integrative approach, involving a systematic assessment of
      diverse species and phenotype measures. As part of the World Congress on Stress
      and Alcoholism, this symposium provided a detailed account of current strategies
      to identify mechanisms underlying the development and progression of AUDs. Dr.
      Sean Farris discussed the integration and organization of transcriptome and
      postmortem human brain data to identify brain regional- and cell type-specific
      differences related to excessive alcohol consumption that are conserved across
      species. Dr. Brien Riley presented the results of a genome-wide association study
      of DSM-IV alcohol dependence; although replication of genetic associations with
      alcohol phenotypes in humans remains challenging, model organism studies show
      that COL6A3, KLF12, and RYR3 affect behavioral responses to ethanol, and provide
      substantial evidence for their role in human alcohol-related traits. Dr. Rob
      Williams expanded upon the systematic characterization of extensive genetic
      genomic resources for quantifying and clarifying phenotypes across species that
      are relevant to precision medicine in human disease. The symposium concluded with
      Dr. Robert Hitzemann's description of transcriptome studies in a mouse model
      selectively bred for high alcohol ("binge-like") consumption and a non-human
      primate model of long-term alcohol consumption. Together, the different
      components of this session provided an overview of systems-based approaches that
      are pioneering the experimental prioritization and validation of novel genes and
      gene networks linked with a range of behavioral phenotypes associated with stress
      and AUDs.

PMID- 30213504
TI  - Seize the opportunity - Recognition and management of functional seizures in
      children.

PMID- 30213505
TI  - Genotype-phenotype correlation: The ultimate challenge in facioscapolohumeral
      muscular dystrophy.

PMID- 30213506
TI  - Mesenchymal stem cells-derived IL-6 activates AMPK/mTOR signaling to inhibit the
      proliferation of reactive astrocytes induced by hypoxic-ischemic brain damage.
AB  - Mesenchymal stem cells (MSCs) treatment is an effective strategy for the
      functional repair of central nervous system (CNS) insults through the production
      of bioactive molecules. We have previously demonstrated that the interleukin-6
      (IL-6) secreted by MSCs plays an anti-apoptotic role in injured astrocytes and
      partly promotes functional recovery in neonatal rats with hypoxic-ischemic brain
      damage (HIBD). However, the mechanisms of IL-6 underlying the proliferation of
      injured astrocytes have not been fully elucidated. In this study, we investigated
      the therapeutic effects of MSCs on astrocyte proliferation in neonatal rats
      subjected to HIBD. A HIBD model was established in Sprague Dawley (SD) rats, and
      MSCs were administered by intracerebroventricular injection 5 days after HIBD.
      Rat primary astrocytes were cultured, subjected to oxygen glucose deprivation
      (OGD) injury and then immediately co-cultured with MSCs in vitro.
      Immunofluorescence staining, Cell Counting Kit (CCK)-8, flow cytometry, Ca2+
      imaging, enzyme-linked immunosorbent assay (ELISA), western blotting, and co
      immunoprecipitation (Co-IP) were performed. We found that MSCs transplantation
      not only promoted the recovery of learning and memory function in HIBD rats but
      also significantly reduced the number of Ki67+/glial fibrillary acidic protein
      (GFAP)+ cells in the hippocampi 7-14 days after HIBD. In addition to increasing
      IL-6 expression in both the hippocampi of HIBD rats and astrocyte culture medium,
      MSCs treatment in vitro significantly increased the expression levels of
      glycoprotein (gp) 130 and phosphorylated AMP-activated protein kinase alpha (p
      AMPKalpha) and decreased the expression levels of p-mammalian target of rapamycin
      (mTOR) and its downstream targets. Furthermore, MSCs treatment induced a protein
      protein interaction between gp130 and p-AMPKalpha. Suppression of IL-6 expression
      in MSCs reversed the above regulatory functions of MSCs in hippocampal
      astrocytes. The utilization of rapamycin further confirmed that mTOR participated
      in the proliferation of reactive astrocytes. These findings suggest that
      endogenous IL-6 produced by MSCs in the HIBD microenvironment provides
      therapeutic advantages by activating AMPK/mTOR signaling, thus reducing the
      proliferation of reactive astrocytes.

PMID- 30213507
TI  - Oncostatin M-induced upregulation of SDF-1 improves Bone marrow stromal cell
      migration in a rat middle cerebral artery occlusion stroke model.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) exhibit potential regenerative
      effects on the injured brain. However, these effects are constrained by their
      limited ability to migrate to the injured site. Oncostatin M (OSM) has been shown
      to affect the proliferation and migration of mesenchymal stem cells. Therefore,
      in the present study, we explored whether OSM improves BMSC migration and
      secretion of growth factors and cytokines in a rat middle cerebral artery
      occlusion (MCAO) stroke model. The effect of OSM on the proliferation and
      apoptosis of rat BMSCs was first assessed in vitro, and the gene and secretion
      levels of factors related to cell nutrition and migration, such as SDF-1 and
      VEGF, were detected. To further explore underlying pathways triggered by OSM,
      BMSCs were treated with OSM in the presence or absence of inhibitors of the STAT3
      and ERK pathways. Effects of OSM on SDF-1 expression in astrocytes and BMSC
      migration were also evaluated. In the rat MCAO model, OSM secretion levels were
      detected in the brain for up to 72 h after model establishment. Ventricle
      injection of OSM alone or OSM combined with caudal vein graft of BMSCs was then
      performed in MCAO stroke rats. After 72 h, production of SDF-1 and grafted BMSCs
      was detected in the lesion areas of the brain, and the nerve function score was
      evaluated. We found that the production of OSM continually increased in the
      brains of MCAO rats from 12 h to 72 h. OSM significantly upregulated SDF-1 in
      BMSCs via the STAT3 and ERK pathways and significantly promoted the expression of
      VEGF and MMP-2. OSM also promoted the secretion of SDF-1 in astrocytes through
      the STAT3 and ERK pathways to in turn enhance BMSC migration. Combination
      treatment with OSM and BMSCs in MCAO rats increased the migration efficiency of
      BMSCs in the brain, which significantly improved neurofunctional recovery while
      reducing the expression of inflammatory mediators and promoting the secretion of
      nutrition factors. Overall, these results show that OSM is highly expressed in
      the brains of MCAO stroke rats and can upregulate SDF-1 to promote BMSC
      migration. Thus, combination treatment with OSM and BMSCs improves the graft
      efficiency of BMSCs and neurofunctional recovery.

PMID- 30213508
TI  - Patients with Peripheral Artery Disease in the COMPASS Trial.

PMID- 30213509
TI  - Continuous Visceral and Distal Perfusion During "Off-pump" Open Thoraco-abdominal
      Repair.

PMID- 30213510
TI  - Rheological and controlled release properties of hydrogels based on mushroom
      hyperbranched polysaccharide and xanthan gum.
AB  - A hyperbranched polysaccharide, coded as TM3a, was extracted from the Pleurotus
      tuber-regium sclerotia. TM3a was hybridized with xanthan gum (XG) by chemical
      crosslinking using sodium trimetaphosphate (STMP) to obtain new hydrogels with
      self-healing and release-controlled properties. The oscillatory rheological
      measurements indicated that chemically crosslinking was happened immediately on
      mixing STMP solutions into the XG-TM3a solutions, and the crosslinked network
      developed slightly as time increased. The resultant hydroges were disturbed into
      the loose structures and regrouped the microstructure in 2 min when a large and a
      small amplitude oscillation were applied in turn, suggesting a self-healable
      property. The XG-TM3a-STMP hydrogels exhibited shear-thinning behavior with yield
      stress. The storage modulus of the XG5-TM3a-STMP hydrogel was 445.2 Pa at 1%
      strain and 243.3 Pa at 100% strain, and yield stress was 160.6 Pa, which was
      higher than the corresponding value of the XG5-STMP hydrogel. The morphological
      observation indicated the aggregates of double helical XG chains exhibited
      directional arrangement, and were combined with the TM3a aggregates to constitute
      a network of hierarchical structures. The hybrid hydrogels with enhanced
      mechanical properties displayed good drug loading efficiencies and sustained drug
      release properties.

PMID- 30213511
TI  - Associations of paternal postpartum depressive symptoms and infant development in
      a Chinese longitudinal study.
AB  - Although fathers actively provide infant care and support to their partners in
      modern societies, data on fathers' difficulties and mental health problems is
      still limited. This study examined paternal postpartum depression and its adverse
      impact on infants, and the possible mediating role of father-infant attachment in
      the link between fathers' depressive symptoms and infants' outcomes. Pregnant
      women and their partners were recruited from the antenatal clinics of two public
      hospitals in Hong Kong. Information about paternal and maternal depression,
      paternal-infant attachment, and infant development were collected at antenatal
      period, 6 weeks and 6 months postpartum. Linear regression was employed to
      examine risk factors for paternal depression symptoms, and mediation analysis was
      conducted to examine the mediating mechanisms. 121 couples joined the
      longitudinal study and completed all the assessments. Paternal postpartum
      depression symptoms were associated with fathers' prenatal depression symptoms,
      and mothers' postpartum depression symptoms. Fathers with postpartum depression
      symptoms experienced reduced paternal-infant attachment, which also acted as
      mediators between postpartum depression in fathers and adverse infants' social
      development. Effective assessment and interventions targeted at preventing or
      identifying and reducing paternal postpartum depression and improving father
      infant relationship would help to lower the risk of infant disorders and poor
      development. Strategies improving the fathers' mental health during antenatal
      period and their partner's psychosocial well-being may also reduce paternal
      postpartum depression.

PMID- 30213512
TI  - Early life experiences: Meaningful differences within and between families.
AB  - Previous research has focused on differences in early life experiences that occur
      between families and their impact on children's development. However, less is
      known about the variations in early life experiences that occur within families.
      Here, 53 British mothers (mean age = 34.46 years; SD = 4.35) of newborn infants
      (mean age = 1.68 months, SD = 0.96) used a smartphone application (app) to
      repeatedly rate their wellbeing and support and to report their baby's and their
      own dietary and sleeping patterns (4 app alerts per week for 3 weeks; 12
      assessments in total). We found that the app was a practicable tool for observing
      early life experiences, and that early life experiences differed on average to a
      greater extent within, rather than between families (59% versus 41% of the total
      variance). We also found preliminary evidence for meaningful associations among
      contemporaneous within-family variations in early life experiences.

PMID- 30213513
TI  - Jejuno-jejunal invagination in a patient with intestinal malrotation.

PMID- 30213514
TI  - Transaxillary endoscopic thyroidectomy: Another approach to offer our patients.

PMID- 30213515
TI  - Giant lumbar incisional hernia reparation by "sandwich" technique.

PMID- 30213516
TI  - Development and validation of a method to record electrophysiological responses
      in direct acoustic cochlear implant subjects.
AB  - Acoustic hearing implants, such as direct acoustic cochlear implants (DACIs), can
      be used to treat profound mixed hearing loss. Electrophysiological responses in
      DACI subjects are of interest to confirm auditory processing intra-operatively,
      and to assist DACI fitting postoperatively. We present two related studies,
      focusing on DACI artifacts and electrophysiological measurements in DACI
      subjects, respectively. In the first study we aimed to characterize DACI
      artifacts, to study the feasibility of measuring frequency-specific
      electrophysiological responses in DACI subjects. Measurements of DACI artifacts
      were collected in a cadaveric head to disentangle possible DACI artifact sources
      and compared to a constructed DACI artifact template. It is shown that for
      moderate stimulation levels, DACI artifacts are mainly dominated by the artifact
      from the radio frequency (RF) communication signal, that can be modeled if the RF
      encoding protocol is known. In a second study, the feasibility of measuring intra
      operative responses, without applying the RF artifact models, in DACI subjects is
      investigated. Auditory steady-state and brainstem responses were measured intra
      operatively in three DACI subjects, immediately after implantation, to confirm
      proper DACI functioning and coupling to the inner ear. Intra-operative responses
      could be measured in two of the three tested subjects. Absence of intra-operative
      responses in the third subject can possibly be explained by the hearing loss,
      attenuation of intra-operative responses, the difference between
      electrophysiological and behavioral threshold, and a temporary threshold shift
      due to the DACI surgery. In conclusion, RF artifacts can be modeled, such that
      electrophysiological responses to frequency-specific stimuli could possibly be
      measured in DACI subjects, and intra-operative responses in DACI subjects can be
      obtained.

PMID- 30213517
TI  - The Tubulin Detyrosination Cycle: Function and Enzymes.
AB  - Microtubules are subjected to a variety of post-translational modifications
      (PTMs). The combination of different alpha- and beta-tubulin isoforms and PTMs
      are referred to as the tubulin code. PTMs are generated by a suite of enzymes
      thought to affect tubulin-interacting proteins. One PTM is the cyclic removal and
      ligation of the C-terminal tyrosine of alpha-tubulin. This has been implicated in
      cellular processes such as mitosis, cardiomyocyte contraction, and neuronal
      function. Recently, vasohibins (VASHs) were identified as the first tubulin
      detyrosinating enzymes, A cell-autonomous role for VASHs in regulating the
      cytoskeleton was unexpected due to their previous association with angiogenesis.
      This review discusses the functionality of the tubulin detyrosination cycle, the
      biology of VASHs, and highlights the emerging questions accompanying this link.

PMID- 30213518
TI  - Novel nano-insulin formulation modulates cytokine secretion and remodeling to
      accelerate diabetic wound healing.
AB  - Little is known about insulin's wound healing capability in normal as well as
      diabetic conditions. We here report specific interaction of silver nanoparticles
      (AgNPs) with insulin by making a ~2 nm thick coat around the AgNPs and its potent
      wound healing efficacy. Characterization of the interaction of human insulin with
      silver nanoparticles showed confirmed alteration of amide-I in insulin whereas
      amide-II and III remained unaltered. Further, nanoparticles protein interaction
      kinetics showed spontaneous interaction at physiological temperature with DeltaG,
      DeltaS, Ea and Ka values -7.48, 0.076, 3.84 kcal mol-1 and 6 * 105 s-1
      respectively. Insulin loaded AgNPs (IAgNPs) showed significant improvement in
      healing activity in vitro (HEKa cells) and in vivo (Wister Rats) in comparison
      with the control in both normal and diabetic conditions. The underlying mechanism
      was attributed to a regulation of the balance between pro (IL-6, TNFalpha) and
      anti-inflammatory cytokines (IL-10) at the wound site to promote faster wound
      remodeling.

PMID- 30213519
TI  - Corrigendum to "Probing the colorectal cancer proteome for biomarkers: Current
      status and perspectives" [J Proteomics Vol. 187 (2018) 93-105].

PMID- 30213520
TI  - Restless legs syndrome in type 2 diabetes mellitus.
AB  - AIMS: This study aimed to investigate the prevalence of restless leg syndrome
      (RLS) in type-2 diabetes mellitus (DM) patients and to determine the risk
      factors. METHODS: Patients were recruited from the Dr. Lutfi Kirdar Kartal
      Training and Research Hospital Diabetes Center. Patients between 18-80 years of
      age and meeting a minimum 5 years diagnosis of type-2 DM were included. All
      patients were examined by the same neurologist in terms of having RLS. The
      diagnosis was made according to the updated International Restless Legs Syndrome
      Study Group consensus criteria. Mimicking conditions such as myalgia, venous
      stasis, leg edema, arthritis, leg cramps, positional discomfort and habitual foot
      tapping were carefully investigated and excluded. Laboratory data, insulin use,
      family history and other related co-morbidities connected to RLS patients were
      recorded. RLS severity assessment was scored and recorded. RESULTS: 318 patients
      were included in the study. The prevalence of RLS in type-2 DM patients was found
      to be 28.3%. RLS prevalence in females was 33.3% and 20.6% in males. 39 patients
      (43.3%) had a family history of RLS. 43 patients with RLS had a co-morbidity link
      with RLS. Any co-morbidity linked to RLS was not seen in 47 patients. The
      prevalence rate of RLS in patients without co-morbidities was 17.1%. Mean
      duration of DM in patients with RLS was 15.6+/-6.7years while in DM patients
      without RLS was 13.7+/-6.3years. The relationship between RLS and the duration of
      diabetes was found to be statically significant. (p=0.025). 68 (75.6%) of
      patients diagnosed with RLS were treated with insulin. A statistical significance
      was found in the development of RLS and insulin usage (p=0.035). CONCLUSIONS:
      This is the first study which shows the RLS prevalence and risk factors in
      Turkish type-2 diabetes mellitus patients. The results indicated that RLS is much
      more frequent in DM patients even after excluding polyneuropathy than in general
      Turkish population. The duration of diabetes and insulin use are related to RLS.

PMID- 30213521
TI  - [Thrombosed external jugular vein saccular aneurysm: Presentation of a case].

PMID- 30213522
TI  - Paeonol attenuates ligation-induced periodontitis in rats by inhibiting
      osteoclastogenesis via regulating Nrf2/NF-kappaB/NFATc1 signaling pathway.
AB  - Paeonol is a natural phenolic compound in Moutan Cortex with multiple biological
      functions, such as anti-inflammatory and anti-oxidant activity. Recent evidence
      has proven that persistent inflammation, oxidative stress, along with nuclear
      factor E2-related factor 2 (Nrf2) signaling dysfunction in periodontium are the
      possible causes of alveolar bone resorption, and ultimately lead to
      periodontitis. The present study was designed to explore the protective effects
      of paeonol on ligation-induced periodontitis in rats, and investigate the
      possible mechanism. We found that treatment with paeonol (40, 80 mg/kg,
      intraperitoneal injection) for 7 days remarkably decreased the expression of
      receptor activator of nuclear factor kappa-B ligand increased the expression of
      osteoprotegrin and inhibited the formation of osteoclasts. This function of
      paeonol might be correlated with its ability to reduce inflammatory factors (IL
      1beta, IL-6 and TNF-alpha) and alleviate oxidative stress (SOD, MDA, GSH and ROS)
      in gingival tissues. Besides, paeonol increased Nrf2 activity. Silence of Nrf2
      using specific siRNA diminished the inhibitory effect of paeonol on NF-kappaB p65
      activation and downstream expression, suggesting that Nrf2 was essential for
      protective effect of paeonol. These results showed that paeonol protected against
      periodontitis-aggravated osteoclastogenesis and alveolar bone lesion via
      regulating Nrf2/NF-kappaB/NFATc1 signaling pathway.

PMID- 30213523
TI  - Molecular Subtypes of Urothelial Bladder Cancer: Results from a Meta-cohort
      Analysis of 2411 Tumors.
AB  - BACKGROUND: Previous molecular subtyping for bladder carcinoma (BLCA) involved
      <450 samples, with diverse classifications. OBJECTIVE: To identify molecular
      subtypes by curating a large BLCA dataset. DESIGN, SETTING, AND PARTICIPANTS:
      Gene expression publicly available were combined and reanalyzed. The dataset
      contained 2411 unique tumors encompassing non-muscle-invasive (NMIBC) and muscle
      invasive BLCA (MIBC). Subtypes were reproduced on The Cancer Genome Atlas,
      UROMOL, and IMvigor210. INTERVENTION: Subtypes were assigned by gene expression.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier analyses were
      performed for subtype-clinical outcome correlations; Chi-square/Fisher exact
      tests were used for subtype-clinicopathological parameters associations. RESULTS
      AND LIMITATIONS: We identified six molecular subtypes with different overall
      survival (OS) and molecular features. Subtype Neural-like (median OS, 87 mo) is
      prevalent in MIBC and characterized by high WNT/beta-catenin signaling. HER2-like
      (107.7 mo) is distributed evenly across NMIBC and MIBC, with higher ERBB2
      amplification and signaling. Papillary-like (>135 mo), an NMIBC subtype enriched
      in urothelial differentiation genes, shows a high frequency of actionable FGFR3
      mutations, amplifications, and FGFR3-TACC3 fusion. Luminal-like (91.7 mo),
      predominantly NMIBC, has higher MAPK signaling and more KRAS and KMT2C/D
      mutations than other subtypes. Mesenchymal-like (MES; 86.6 mo) and Squamous-cell
      carcinoma-like (SCC; 20.6 mo) are predominant in MIBC. MES is high in AXL
      signaling, whereas SCC has elevated PD1, CTLA4 signaling, and macrophage M2
      infiltration. About 20% of NMIBCs show MIBC subtype traits and a lower 5-yr OS
      rate than Papillary-like NMIBC (81% vs 96%). The main limitations of our study
      are the incomplete clinical annotation, and the analyses were based on
      transcriptome subset due to comparisons across gene expression quantification
      technologies. CONCLUSIONS: BLCA can be stratified into six molecular subtypes.
      NMIBC, with a high risk of progression, displays the molecular features of MIBC.
      PATIENT SUMMARY: Biomarkers are urgently needed to guide patient treatment
      selection and avoid unnecessary toxicities in those who fail to respond. We
      believe molecular subtyping is a promising way to tailor disease management for
      those who will benefit most.

PMID- 30213524
TI  - Influence of light-cured luting agents and associated factors on the color of
      ceramic laminate veneers: A systematic review of in vitro studies.
AB  - OBJECTIVE: The luting agent plays a significant role in the appearance of ceramic
      laminate veneers (CLV), allowing improved/stable shade matching with adjacent
      teeth. A systematic review was conducted to investigate the influence of light
      cured luting agents and color-associated factors aiming to draw guidelines for
      stable shade matching of CLV. The paper has also given an overview of the
      compositional characteristics of all luting agents and ceramic systems whose
      performance was presented herein. METHODS: A search of in vitro studies that
      quantitatively investigated the influence of light-cured luting agents on the
      color of CLV was conducted. PubMed/MedLine, Cochrane Library, SciVerse Scopus and
      Web of Science databases were explored until December 2017 with no year limit.
      Data regarding the effect of light-cured luting agent, ceramic systems, effect of
      background, accelerated aging and surface treatments on color change were
      collected. A meta-analysis was not possible due to heterogeneity of data.
      RESULTS: After duplicates' removal, 3630 studies were identified, 48 were
      selected for full-text analysis, and 21 remaining papers met the inclusion
      criteria and were included in this systematic review. SIGNIFICANCE: Considering
      the shade aspects of luting agents, translucency and value showed the greatest
      visible color differences for CLVs. The effect of luting agent shade on the color
      of veneers is greatly affected by ceramic thickness and opacity.

PMID- 30213525
TI  - Psychotropic medicines use in Residents And Culture: Influencing Clinical
      Excellence (PRACTICE) tool(c). A development and content validation study.
AB  - INTRODUCTION: Psychotropic medicines are often prescribed in nursing homes to
      manage behavioral and psychological symptoms of dementia despite marginal
      clinical effects alongside harmful adverse events. Organizational culture has
      been identified as a key factor that contributes to the high-level prescribing of
      psychotropic medicines in nursing homes. There are gaps in existing tools used to
      link organizational culture to the use of psychotropic medicines. The aim of this
      research was to develop and content validate a tool that evaluates organizational
      culture specific to the use of psychotropic medicines, named the Psychotropic
      medicines use in Residents And Culture: Influencing Clinical Excellence
      (PRACTICE) tool(c). METHODS: Schein's theory of organizational culture was used
      to guide the development and content validation of the PRACTICE tool(c). The
      PRACTICE tool(c) was developed based on a comprehensive systematic review,
      qualitative research and generated by the research team. Content validity was
      assessed using the CVI (Content Validity Index). The content relevance and
      importance of the PRACTICE tool(c) items were rated by an expert panel with
      relevant knowledge and experience. Any modified or re-worded items were presented
      to the panel members in a subsequent survey for re-rating. RESULTS: Across the
      two rounds, the PRACTICE tool(c) had 68 items that assessed all aspects of
      culture according to Schein's theory. Sixty-two items out of 68 (91%) met
      predefined cut-off values (>=0.78) for the I -CVI. The remaining six items (9%)
      did not fully meet the cut-off values but were deemed important to be included in
      the tool based on the systematic review, qualitative research and discussions
      with the research team. CONCLUSIONS: The PRACTICE tool(c) is a step forward in
      validating an instrument that will help inform managers and policy makers to
      identify target areas for improvement to create a culture of appropriate
      psychotropic prescribing in nursing homes.

PMID- 30213526
TI  - FOREWORD: Quality Improvement Part II.

PMID- 30213527
TI  - Modeling Causal Relationships in Quality Improvement.
AB  - Taking the time to plan a quality improvement project before starting the project
      improves the likelihood of success. Understanding the tools that can be utilized
      for identification of a problem, the causes behind it, and the development of the
      theoretical framework of the planned improvement are crucial. Fishbone diagrams
      or cause and effect diagrams are often utilized to identify the root causes
      leading to an identified problem. Keydriver diagrams can provide the structure
      for a quality improvement project, establishing the aim and identifying the
      drivers and interventions that lead to change. This paper reviews these two
      quality improvement tools. When beginning a quality improvement project, several
      tools can be used to begin identifying where to target efforts. Utilizing process
      maps and failure modes and effects analysis (FMEA) can help define a process,
      identify failures, and develop interventions to be considered. Process maps
      identify potential gaps or excess steps and reveal sequential relationships.
      FMEAs aid in the development of causal relationships between a failure mode and
      its effects, priming the quality improver to create interventions. An additional
      way to model causal relationships is with fishbone diagrams and key driver
      diagrams. The fishbone diagram enables teams to consider why a problem has
      occurred and search for the root causes. The key driver diagram provides the
      ultimate aim of the project, identifies the drivers which will affect
      accomplishing the aim, and the interventions that affect the identified drivers.
      This paper will carefully examine both fishbone diagrams and key driver diagrams.

PMID- 30213528
TI  - FOREWORD: Quality Improvement Part I.

PMID- 30213529
TI  - Tolerance to vitrification of rat embryos at various developmental stages.
AB  - Numerous genetically engineered rat strains have been produced via genome
      editing. Although freezing of embryos is helpful for the production and storage
      of these valuable strains, the tolerance to freezing of embryos varies at each
      developmental stage of the embryo. This study examined the tolerance to freezing
      of rat embryos at various developmental stages, particularly at the pronuclear
      stage. Embryos that had developed to the pronuclear, 2-cell, and morula stages
      were frozen via vitrification using ethylene glycol- and propylene glycol-based
      solutions. More than 90% of the embryos at all developmental stages survived
      after warming. The developmental rates to offspring of thawed embryos at the
      pronuclear, 2-cell, and morula stages were 19%, 41%, and 52%, respectively.
      Pronuclear stage embryos between the early and late developmental stages were
      then vitrified. The developmental rates to offspring of the thawed pronuclear
      stage embryos collected at 24, 28, and 31 h after the induction of ovulation were
      17%, 21%, and 23%, respectively. These results indicated that the tolerance to
      vitrification of rat embryos increased with the development of embryos. The
      establishment of vitrification method of rat embryos at various developmental
      stages is helpful for improving the production and storage of valuable rat
      strains used for biomedical science.

PMID- 30213530
TI  - Toward genome editing in X-linked RP-development of a mouse model with specific
      treatment relevant features.
AB  - Genome editing represents a powerful tool to treat inherited disorders. Highly
      specific endonucleases induce a DNA double strand break near the mutant site,
      which is subsequently repaired by cellular DNA repair mechanisms that involve the
      presence of a wild type template DNA. In vivo applications of this strategy are
      still rare, in part due to the absence of appropriate animal models carrying
      human disease mutations and knowledge of the efficient targeting of
      endonucleases. Here we report the generation and characterization of a new mouse
      model for X-linked retinitis pigmentosa (XLRP) carrying a point mutation in the
      mutational hotspot exon ORF15 of the RPGR gene as well as a recognition site for
      the homing endonuclease I-SceI. Presence of the genomic modifications was
      verified at the RNA and protein levels. The mutant protein was observed at low
      levels. Optical coherence tomography studies revealed a slowly progressive
      retinal degeneration with photoreceptor loss starting at 9 months of age,
      paralleling the onset of functional deficits as seen in the electroretinogram.
      Early changes to the outer retinal bands can be used as biomarker during
      treatment applications. We further show for the first time efficient targeting
      using the I-SceI enzyme at the genomic locus in a proof of concept in
      photoreceptors following adeno-associated virus mediated gene transfer in vivo.
      Taken together, our studies not only provide a human-XLRP disease model but also
      act as a platform to design genome editing technology for retinal degenerative
      diseases using the currently available endonucleases.

PMID- 30213531
TI  - Interleukin-6 serum levels predict surgical intervention in infants with
      necrotizing enterocolitis.
AB  - BACKGROUND: Symptoms at suspicion of necrotizing enterocolitis (NEC) are often
      nonspecific and several biomarkers have been evaluated for their discriminative
      power to both diagnose and predict the course from NEC suspicion to complicated
      disease requiring surgical intervention. Thus, we aimed to assess the utility of
      interleukin-6 (IL-6) to predict surgical intervention in infants suffering from
      NEC and, furthermore, to discriminate infants with starting NEC or late-onset
      sepsis (LOS). METHODS: IL-6 serum levels at disease onset were retrospectively
      analyzed in 24 infants suffering from NEC as well as 16 neonates with LOS.
      RESULTS: IL-6 serum levels at disease onset were significantly higher in infants
      suffering from NEC necessitating surgical intervention in the disease course
      compared to infants with medical NEC (5000 [785-5000] vs. 370 [78-4716] pg/ml, p
      = 0.0008) as well as gram-positive LOS (5000 [785-5000] vs. 84 [12-269] pg/ml, p
      = 0.0001). Infants suffering from gram-negative LOS exhibited elevated IL-6 serum
      levels at disease onset comparable to infants with surgical NEC (5000 [1919-5000]
      vs. 5000 [785-5000] pg/ml, p = 1.00). CONCLUSION: The proinflammatory cytokine IL
      6 appears to be a promising marker to distinguish surgical NEC from medical NEC
      at the onset of disease but cannot discriminate between surgical NEC and gram
      negative LOS. LEVEL OF EVIDENCE: II.

PMID- 30213532
TI  - Assessing Quality of Life for Pets with Dermatologic Disease and Their Owners.
AB  - Quality of life (QoL) is defined as "the degree to which an individual enjoys his
      or her life." In canine dermatology, 2 research groups have developed and
      validated questionnaires for QoL assessment in dogs with dermatologic conditions,
      the first being limited to canine atopic dermatitis, and the second one
      applicable to all skin conditions. A third group is working on the validation of
      a different QoL questionnaire coupled with a treatment success assessment tool.
      In general, there is an inverse correlation between QoL and pruritus.

PMID- 30213533
TI  - Canine Perianal Fistulas: Clinical Presentation, Pathogenesis, and Management.
AB  - Canine perianal fistulas are painful sinus tracts and ulcers that spontaneously
      develop in the skin around the anus. Middle-aged German shepherd dogs are most
      commonly affected and may have a genetic susceptibility. Although the disease was
      once believed related to conformational factors and primarily managed surgically,
      an immune-mediated pathogenesis is now recognized. Long-term medical management
      with immunomodulatory agents has become standard of care for canine perianal
      fistulas. Perianal fistulas can be debilitating and have a negative impact on
      quality of life of dogs and owners. Accurate diagnosis and aggressive medical
      therapy are key to successful management of canine perianal fistulas.

PMID- 30213534
TI  - Severity of Obstructive Sleep Apnea Is Positively Associated With the Presence of
      Carotid Artery Atheromas.
AB  - PURPOSE: Hypoxemia and hypertension caused by obstructive sleep apnea (OSA) often
      result in atherosclerosis of the carotid and coronary vessels and heightened risk
      of stroke and myocardial infarction (MI). Therefore, this study investigated
      whether severity of OSA, based on the apnea-hypopnea index (AHI), is associated
      with the presence of calcified carotid artery (atherosclerotic) plaque (CCAP)
      seen on panoramic images (PIs). MATERIALS AND METHODS: Using a cross-sectional
      study design, the electronic medical records and PIs of all male patients
      referred from the sleep medicine service to the dental service from 2010 through
      2016 were reviewed. The predictor variable was the patients' OSA intensity level
      as defined by the American Academy of Sleep Medicine based on the AHI score. The
      outcome variable was the presence of CCAP on the PI. Other variables of interest,
      that is, demographic and atherogenic risk factors (age, body mass index,
      diabetes, hypertension, and hyperlipidemia), were included in a multivariate
      analysis to assess the association of OSA with CCAP. RESULTS: The study sample
      consisted of 108 men (mean age, 54.7 +/- 13.5 yr). Approximately one third (n =
      33; 30.6%) presented with CCAP and this group was significantly older with
      greater odds of co-diagnosis of diabetes (P < .05). Patients with more "severe"
      OSA showed significantly greater odds of having CCAP on their PIs compared with
      those with "milder" OSA (odds ratio = 1.035; 95% confidence interval, 1.008
      1.062; P = .010) when adjusted for confounders. CONCLUSION: There is a
      significant association between severity of OSA and the presence of CCAP visible
      on PI. These atherosclerotic plaques are "risk factors" for stroke and "risk
      indicators" for future MI; therefore, clinicians providing corrective airway
      surgery for these patients and noting concomitant CCAP on PI should refer these
      patients for a thorough cerebrovascular and cardiovascular workup.

PMID- 30213535
TI  - Polyester Urethane Implants for Orbital Trapdoor Fracture Repair in Children.
AB  - PURPOSE: The objective of this study was to present the surgical and clinical
      outcomes of polyester urethane implants in orbital trapdoor fracture repair in
      children. This is the first study reporting on the use of polyester urethane
      implants to repair orbital fractures. MATERIALS AND METHODS: A retrospective
      review was performed of children with orbital trapdoor fracture who underwent
      surgical repair in the authors' medical center over 6 years. The trapdoor
      fracture diagnosis was based on clinical and computed topographic findings.
      RESULTS: Eight patients with trapdoor fracture were identified. All cases were
      repaired by polyester urethane implant placement. Patients' mean age was 13.5
      years and mean follow-up was 13.6 months. All patients had orbital floor
      fractures. Two fractures also involved the medial wall. Seven patients had
      inferior rectus muscle entrapment and 1 had medial rectus muscle entrapment.
      Three patients had residual diplopia on extreme upgaze after the surgical repair.
      No patient had enophthalmos or infraorbital paresthesia at the end of follow-up.
      No postoperative complications associated with the used material were reported.
      CONCLUSION: The polyester urethane implant is a reliable, safe, inexpensive, and
      effective implant for trapdoor fracture repair in children. It can serve as a
      promising alternative to implants fabricated from other synthetic materials for
      orbital floor fracture repair.

PMID- 30213537
TI  - Spermatogenesis as a tool for staging gonad development in the gonochoric
      appendicularian Oikopleura dioica Fol 1872.
AB  - Oikopleura dioica, the only gonochoric species among appendicularians, has a
      spematozoon with a mid-piece and a conspicuous acrosome that, during
      fertilisation, undergoes a reaction forming an acrosomal process. To provide more
      insight into the spermatogenesis of a holoplanktonic tunicate species that
      completes its life cycle in three to five days, changes in the testis during
      individual growth have been examined. Spermatogenesis has been subdivided into
      seven stages based on ultrastructural features during the formation and
      organisation of the male gonad and the relationships between its macroscopic
      anatomy and the events of sperm differentiation. Gametes undergo highly
      synchronised differentiation due to the presence of widespread syncytial
      structures. Both meiosis and spermiogenesis are brief, and the passage from
      spermatocytes to spermatids involves a progressive segregation of the germ cells
      from the syncytial mass with the formation of large cytoplasmic bridges and
      volume reduction for nucleus compacting and cytoplasmic material changing. The
      nucleus is small and penetrated anteriorly by a complex acrosome and posteriorly
      by the distal centriole and part of the flagellum. In spermatids, the single,
      large mitochondrion appears laterally to the nucleus, and finally, in
      spermatozoa, it migrates into the mid-piece, wrapping the proximal portion of the
      axoneme. Because this mitochondrial position is reached only in the late phases
      of spermatogenesis, it suggests that appendicularians have derived oligopyrenic
      sperms in which the small nucleus results from adaptation to the assembly of
      numerous spermatozoa inside the narrow space of the testis compacted in the
      genital cavity. The formulation of a staging system of gonad development in a
      model tunicate species known for having the most compacted genome in chordates
      led to a comparison of histological observations with recent molecular data,
      improving the characterisation of its biology and life cycle in light of
      evolutionary implications.

PMID- 30213536
TI  - Extrahepatic manifestations and HEV, the genotype matters.

PMID- 30213538
TI  - Cas9 ribonucleoprotein complex allows direct and rapid analysis of coding and
      noncoding regions of target genes in Pleurodeles waltl development and
      regeneration.
AB  - Newts have remarkable ability to regenerate their organs and have been used in
      research for centuries. However, the laborious work of breeding has hampered
      reverse genetics strategies in newt. Here, we present simple and efficient gene
      knockout using Cas9 ribonucleoprotein complex (RNP) in Pleurodeles waltl, a
      species suitable for regenerative biology studies using reverse genetics. Most of
      the founders exhibited severe phenotypes against each target gene (tyrosinase,
      pax6, tbx5); notably, all tyrosinase Cas9 RNP-injected embryos showed complete
      albinism. Moreover, amplicon sequencing analysis of Cas9 RNP-injected embryos
      revealed virtually complete biallelic disruption at target loci in founders,
      allowing direct phenotype analysis in the F0 generation. In addition, we
      demonstrated the generation of tyrosinase null F1 offspring within a year.
      Finally, we expanded this approach to the analysis of noncoding regulatory
      elements by targeting limb-specific enhancer of sonic hedgehog, known as the zone
      of polarizing activity regulatory sequence (ZRS; also called MFCS1). Disruption
      of ZRS led to digit deformation in limb regeneration. From these results, we are
      confident that this highly efficient gene knockout method will accelerate gene
      functional analysis in the post-genome era of salamanders.

PMID- 30213540
TI  - Serum plasminogen as a potential biomarker for the effects of low-dose benzene
      exposure.
AB  - Exposure to low-dose benzene may lead to hematotoxicity and cause health
      problems. Though peripheral blood cell count is widely used in benzene exposure
      assessment and health risk assessment, the reports regarding the effects of low
      dose benzene exposure on blood cell count remain inconsistent. To uncover more
      sensitive biomarkers for low-dose benzene exposure, our previous study screened
      out three potential serum proteins-plasminogen (PLG), platelet basic protein
      (PBP) and apolipoprotein B100 (ApoB100)-as biomarkers from chronic benzene
      poisoning patients by using proteomic analysis. In the present study, we verify
      the three serum proteins as biomarkers for the effects of low-dose benzene
      exposure in a large low-dose benzene exposure population. The study showed that
      serum PLG increased in benzene exposed workers and was positively correlated with
      benzene exposure levels. However, no significant changes in serum PBP or ApoB100
      were found in the benzene exposed workers. To explore whether the candidate serum
      proteins are associated with hematotoxicity, the study population was regrouped
      into two groups, based on their WBC counts. Our results showed that the workers
      with high serum PLG levels suffered higher risk of WBC abnormalities than did
      workers with low serum PLG levels. Taken together, these findings indicate that
      the increase in serum PLG might be associated with low-dose benzene exposure and
      benzene-induced hematotoxicity. Thus, we suggest serum PLG could be used as a
      potential biomarker for the effects of low-dose benzene exposure.

PMID- 30213539
TI  - The kinases PIG-1 and PAR-1 act in redundant pathways to regulate asymmetric
      division in the EMS blastomere of C. elegans.
AB  - The PAR-1 kinase of C. elegans is localized to the posterior of the one-cell
      embryo and its mutations affect asymmetric spindle placement and partitioning of
      cytoplasmic components in the first cell cycle. However, par-1 mutations do not
      cause failure to restrict the anterior PAR polarity complex to the same extent as
      mutations in the posteriorly localized PAR-2 protein. Further, it has been
      difficult to examine the role of PAR-1 in subsequent divisions due to the early
      defects in par-1 mutant embryos. Here we show that the PIG-1 kinase acts
      redundantly with PAR-1 to restrict the anterior PAR-3 protein for normal polarity
      in the one-cell embryo. By using a temperature sensitive allele of par-1, which
      exhibits enhanced lethality when combined with a pig-1 mutation, we have further
      explored roles for these genes in subsequent divisions. We find that both PIG-1
      and PAR-1 regulate spindle orientation in the EMS blastomere of the four-cell
      stage embryo to ensure that it undergoes an asymmetric division. In this cell,
      PIG-1 and PAR-1 act in parallel pathways for spindle positioning, PIG-1 in the
      MES-1/SRC-1 pathway and PAR-1 in the Wnt pathway.

PMID- 30213541
TI  - A review of the innovative gas separation membrane bioreactor with mechanisms for
      integrated production and purification of biohydrogen.
AB  - This review article focuses on an assessment of the innovative Gas Separation
      Membrane Bioreactor (GS-MBR), which is an emerging technology because of its
      potential for in-situ biohydrogen production and separation. The GS-MBR, as a
      special membrane bioreactor, enriches CO2 directly from the headspace of the
      anaerobic H2 fermentation process. CO2 can be fed as a substrate to auxiliary
      photo-bioreactors to grow microalgae as a promising raw material for
      biocatalyzed, dark fermentative H2-evolution. Overall, these features make the GS
      MBR worthy of study. To the best of the authors' knowledge, the GS-MBR has not
      been studied in detail to date; hence, a comprehensive review of this topic will
      be useful to the scientific community.

PMID- 30213542
TI  - Quorum sensing and quenching in membrane bioreactors: Opportunities and
      challenges for biofouling control.
AB  - Membrane biofouling, due to biofilm growth after planktonic bacteria attachment
      to a membrane, is a major bottleneck limiting the energy-efficient operation and
      maintenance of membrane bioreactors (MBRs). Microbial communications, known as
      quorum sensing (QS), are responsible for this biofouling behavior. Novel
      strategies for stopping this communication, known as quorum quenching (QQ),
      appear to be successful for biofouling control in MBRs used for wastewater
      treatment. This review describes recent information regarding the signal
      molecules and mechanisms responsible for QS behaviors, promising approaches for
      QQ (enzymatic, bacterial, fungal, photocatalytic, mimicking, and biostimulating
      methods), and efficient fabrication and use of QQ media for MBR applications. We
      discuss the opportunities and challenges of QQ techniques for their further
      improvement and practical use in MBRs.

PMID- 30213543
TI  - Higher Serum C-reactive Protein Level Represents the Immunosuppressive Tumor
      Microenvironment in Patients With Clear Cell Renal Cell Carcinoma.
AB  - INTRODUCTION: C-reactive protein (CRP), a representative inflammatory marker,
      could serve as a biomarker in renal cell carcinoma because CRP is an important
      prognostic factor. However, its detailed mechanism remains unknown. This study
      showed that higher CRP levels correlated with the tumor immune microenvironment,
      which leads to a worse prognosis. These findings can help to clarify the
      underlying mechanisms between the presence of systemic inflammatory reaction and
      prognosis. The aim of this study is to investigate the association between tumor
      immune microenvironment and CRP in patients with renal cell carcinoma (RCC) to
      explore the underlying mechanisms between CRP level and prognosis. PATIENTS AND
      METHODS: Immunohistochemical measurement of CD4, CD8, CD163 (M2 macrophages), and
      Foxp3 (Regulatory T [Treg] cells) was performed in patients with clear-cell RCC
      (n = 111) treated with radical or partial nephrectomy at our institution. The
      association between immunohistochemical status and preoperative serum CRP level
      and cancer-specific survival (CSS) was analyzed. RESULTS: Thirty-three patients
      (30%) had a high CRP level (>= 5.0 mg/L), and the CSS rate was significantly
      worse among these patients than among the remaining patients (P < .001). In
      patients with strong infiltration of CD8+, Foxp3+, or CD163+ cells, CRP levels
      were significantly higher (P = .041, P = .001, and P = .035, respectively), and
      CSS was significantly worse compared with patients with weak infiltration (P =
      .040, P = .026, and P < .001, respectively). In multivariate analysis, strong
      CD163+ cells infiltration (P = .001) as well as pathologic T3 (P = .036), lymph
      node involvement (P = .007), distant metastasis (P < .001), and Fuhrman nuclear
      grade 4 (P = .003) were independent prognostic factors for CSS. CONCLUSIONS:
      Infiltration of the immunosuppressive cells known as Tregs and M2 macrophages in
      the tumor microenvironment is associated with higher CRP and poor prognosis in
      patients with clear-cell RCC. CRP could reflect an immunosuppressive
      microenvironment.

PMID- 30213544
TI  - Conventional Polyethylene in Total Hip Arthroplasty in Young Patients:
      Survivorship, Wear Analysis, and Clinical Outcomes Between 15 and 20 Years.
AB  - BACKGROUND: Total hip arthroplasty (THA) remains a successful procedure for most
      patients. However, there is a paucity of information regarding the long-term
      performance of conventional polyethylene (CPE) bearings in young patients
      undergoing THA. METHODS: After accounting for incomplete follow-up of a
      prospective cohort of 123 THAs in patients <=50 years, we performed a
      retrospective review of 101 hips in 84 patients (82.1%) with an average 17.1-year
      follow-up (14.7-19.6 years). Outcomes of interest included linear and volumetric
      wear, clinical outcome scores, implant survivorship, and patient mortality. Wear
      rates were calculated using Martell Software. RESULTS: Wear analysis revealed
      median linear and volumetric wear rates of 0.106 mm/y (confidence interval, 0.079
      0.133) and 43.58 mm3/y (confidence interval, 33.4-53.75). The modified Harris hip
      scores improved by 36 points while University of California, Los Angeles activity
      scores improved by 2.0 points at 15-year follow-up (P < .0001). Twenty-two hips
      (21.8%) were revised, 13 of which (12.8%) were for wear-related causes at an
      average of 14.9 years (range, 9.2-21 years) from index arthroplasty. There was
      significantly higher mortality in patients with a preoperative diagnosis of
      inflammatory avascular necrosis (P = .015). CONCLUSION: Because CPE was commonly
      used in THA over the last 25 years, it is important to understand its
      implications on the growing revision burden. Significant concerns exist with
      regard to the long-term durability of CPE bearings in young, moderately active
      patients 15 years after THA. These patients should be followed closely for wear
      related problems. Our results should be used as a comparison when evaluating the
      outcomes of more modern bearing surface combinations.

PMID- 30213545
TI  - Information and learning in processing adjective inflection.
AB  - We investigated the processing of inflected Serbian adjective forms to bring
      together quantitative linguistic measures from two frameworks - information
      theory and discrimination learning. From each framework we derived several
      quantitative descriptions of an inflectional morphological system and fitted two
      separate regression models to the processing latencies that were elicited by
      inflected adjectival forms presented in a visual lexical decision task. The
      model, which was based on lexical distributional and information theory revealed
      a dynamic interplay of information. The information was sensitive to syntagmatic
      and paradigmatic dimensions of variation; the paradigmatic information
      (formalized as respective relative entropies) was also modulated by lemma
      frequency. The discrimination learning based model revealed an equally complex
      pattern, involving several learning-based variables. The two models revealed
      strikingly similar patterns of results, as confirmed by the very high proportion
      of shared variance in model predictions (85.83%). Our findings add to the body of
      research demonstrating that complex morphological phenomena can arise as a
      consequence of the basic principles of discrimination learning. Learning
      discriminatively about inflectional paradigms and classes, and about their
      contextual or syntagmatic embedding, sheds light on human language-processing
      efficiency and on the fascinating complexity of naturally emerged language
      systems.

PMID- 30213546
TI  - Simple drop cast method for enumeration of bacteriophages.
AB  - Phage enumeration is a basic prerequisite for application of phages in
      industrial, medical and other processes. Double layer agar (DLA) plaque assay is
      the classical method employed for isolation, detection as well as enumeration of
      phage particles in a solution. However, DLA method is considered cumbersome due
      to its specific temperature requirements and need for one petriplate with two
      agar layers for each phage sample. We are proposing a drop cast method for
      enumeration of phages which is comparatively easier and cost effective than
      classical DLA method as single layer of agar without any specific temperature
      condition is required. Added advantage of this method is that 7-10 dilutions of
      phage suspension can be enumerated on a single agar plate in contrast to one
      dilution per plate as required in DLA method. Although standard deviation in
      phage count was higher in the proposed method than DLA method, still drop cast
      method provided first-approximation phage titer which can be further validated by
      DLA method for more accuracy. Hence, the present method can be considered
      reliable, easy and cost effective for determining approximate phage count in an
      unknown phage suspension.

PMID- 30213547
TI  - Using spike train distances to identify the most discriminative neuronal
      subpopulation.
AB  - BACKGROUND: Spike trains of multiple neurons can be analyzed following the summed
      population (SP) or the labeled line (LL) hypothesis. Responses to external
      stimuli are generated by a neuronal population as a whole or the individual
      neurons have encoding capacities of their own. The SPIKE-distance estimated
      either for a single, pooled spike train over a population or for each neuron
      separately can serve to quantify these responses. NEW METHOD: For the SP case we
      compare three algorithms that search for the most discriminative subpopulation
      over all stimulus pairs. For the LL case we introduce a new algorithm that
      combines neurons that individually separate different pairs of stimuli best.
      RESULTS: The best approach for SP is a brute force search over all possible
      subpopulations. However, it is only feasible for small populations. For more
      realistic settings, simulated annealing clearly outperforms gradient algorithms
      with only a limited increase in computational load. Our novel LL approach can
      handle very involved coding scenarios despite its computational ease. COMPARISON
      WITH EXISTING METHODS: Spike train distances have been extended to the analysis
      of neural populations interpolating between SP and LL coding. This includes
      parametrizing the importance of distinguishing spikes being fired in different
      neurons. Yet, these approaches only consider the population as a whole. The
      explicit focus on subpopulations render our algorithms complimentary.
      CONCLUSIONS: The spectrum of encoding possibilities in neural populations is
      broad. The SP and LL cases are two extremes for which our algorithms provide
      correct identification results.

PMID- 30213548
TI  - Self-similarity and multifractality in human brain activity: A wavelet-based
      analysis of scale-free brain dynamics.
AB  - BACKGROUND: The temporal structure of macroscopic brain activity displays both
      oscillatory and scale-free dynamics. While the functional relevance of neural
      oscillations has been largely investigated, both the nature and the role of scale
      free dynamics in brain processing have been disputed. NEW METHOD: Here, we offer
      a novel method to rigorously enrich the characterization of scale-free brain
      activity using a robust wavelet-based assessment of self-similarity and
      multifractality. For this, we analyzed human brain activity recorded with
      magnetoencephalography (MEG) while participants were at rest or performing a
      visual motion discrimination task. RESULTS: First, we report consistent infraslow
      (from 0.1 to 1.5 Hz) scale-free dynamics (i.e., self-similarity and
      multifractality) in resting-state and task data. Second, we observed a fronto
      occipital gradient of self-similarity reminiscent of the known hierarchy of
      temporal scales from sensory to higher-order cortices; the anatomical gradient
      was more pronounced in task than in rest. Third, we observed a significant
      increase of multifractality during task as compared to rest. Additionally, the
      decrease in self-similarity and the increase in multifractality from rest to task
      were negatively correlated in regions involved in the task, suggesting a shift
      from structured global temporal dynamics in resting-state to locally bursty and
      non Gaussian scale-free structures during task. COMPARISON WITH EXISTING
      METHOD(S): We showed that the wavelet leader based multifractal approach extends
      power spectrum estimation methods in the way of characterizing finely scale-free
      brain dynamics. CONCLUSIONS: Altogether, our approach provides novel fine-grained
      characterizations of scale-free dynamics in human brain activity.

PMID- 30213549
TI  - Chemical warfare agent NOVICHOK - mini-review of available data.
AB  - The Cold War period is characterized by the infighting between the Western
      countries and the USSR in diverse areas. One of such fields was development of
      the weapons of mass destruction. Within various programs on both sides, a wide
      scale of different agents have been developed. However, information about some of
      them are still protected under the designation "top secret". Notwithstanding, in
      history several cases are known when such information beheld the daylight. One of
      such cases was the program FOLIANT and NOVICHOK. Both programs were developed by
      the USSR as a reaction to English/American invention of VX agent. If at least a
      part of available information is truthful, we can allege that these compounds
      belong among the most toxic synthetic agents ever. Within this contribution, we
      have reviewed available Eastern and Western data about the A-agents and their
      precursors, so-called NOVICHOKs, including their history, synthesis, physical
      chemical properties, pharmacological characteristics and clinical manifestation.

PMID- 30213550
TI  - Commercial octopus species from different geographical origins: Levels of
      polycyclic aromatic hydrocarbons and potential health risks for consumers.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants that have been
      raising global concern due to their carcinogenic and mutagenic properties. A
      total of 18 PAHs (16 USEPA priority compounds, benzo(j)fluoranthene and
      dibenzo(a,l)pyrene) were assessed in the edible tissues of raw octopus (Octopus
      vulgaris, Octopus maya, and Eledone cirrhosa) from six geographical origins
      available to Portuguese consumers. Inter- and intra-species comparison was
      statistically performed. The concentrations of total PAHs (?PAHs) ranged between
      8.59 and 12.8 MUg/kg w.w. Octopus vulgaris caught in northwest Atlantic Ocean
      presented SigmaPAHs significantly higher than those captured in Pacific Ocean and
      Mediterranean Sea, as well as than the other characterized species from western
      central and northeast Atlantic Ocean. PAHs with 2-3 rings were the predominant
      compounds (86-92% of ?PAHs) but diagnostic ratios indicated the existence of
      pyrogenic sources in addition to petrogenic sources. Known and possible/probable
      carcinogenic compounds represented 11-21% of SigmaPAHs. World and Portuguese per
      capita ingestion of ?PAHs due to cephalopods consumption varied between 1.62-2.55
      * 10-4 and 7.09-11.2 * 10-4 MUg/kg body weight per day, respectively. Potential
      risks estimated for low and high consumers according to USEPA methodology
      suggested that a regular consumption of raw octopus does not pose public health
      risks.

PMID- 30213551
TI  - First study on trichothecene and zearalenone exposure of the Romanian population
      through wheat-based products consumption.
AB  - In this study, a dietary exposure assessment of mycotoxins was conducted for the
      Romanian population using the contamination data of a various categories of wheat
      based products for direct human consumption. Wheat-based foods (n = 181)
      commercialized in Romania, including flour, bread, biscuits, breakfast cereals
      and pasta, were evaluated by GC-QqQ-MS/MS for the occurrence of deoxynivalenol
      (DON), 3-acetyldeoxynivalenol (3AcDON), 15-acetyldeoxynivalenol (15AcDON),
      fusarenon-X, nivalenol, HT-2 and T-2 toxins, diacetoxyscirpenol, neosolaniol and
      zearalenone (ZEA). DON and 15AcDON were detected in 63 and 5% of all the analyzed
      samples, whereas 13-AcDON, HT-2, T-2, NIV and ZEA were not detected. Exposure of
      Romanian adult population was assessed, the EDIs for the sum of
      DON+3AcDON+15AcDON were 669 ng kg-1 bw day-1 at low-bound estimation, and 690 ng
      kg-1 bw day-1 at upper-bound estimation, being lower than the TDI set (1000 ng kg
      1 bw day-1).

PMID- 30213552
TI  - Cadmium alters heat shock protein pathways in SN56 cholinergic neurons, leading
      to Abeta and phosphorylated Tau protein generation and cell death.
AB  - Cadmium, a neurotoxic environmental compound, produces cognitive disorders,
      although the mechanism remains unknown. Cadmium induces a more pronounced cell
      death on cholinergic neurons from basal forebrain (BF), mediated, in part, by
      increase in Abeta and total and phosphorylated Tau protein levels, which may
      explain cadmium effects on learning and memory processes. Cadmium downregulates
      the expression of heat shock proteins (HSPs) HSP 90, HSP70 and HSP27, and of
      HSF1, the master regulator of the HSP pathway. HSPs proteins reduce the
      production of Abeta and phosphorylated Tau proteins and avoid cell death pathways
      induction. Thus, we hypothesized that cadmium induced the production of Abeta and
      Tau proteins by HSP pathway disruption through HSF1 expression alteration,
      leading to BF cholinergic neurons cell death. Our results show that cadmium
      downregulates HSF1, leading to HSP90, HSP70 and HSP27 gene expression
      downregulation in BF SN56 cholinergic neurons. In addition, cadmium induced Abeta
      and total and phosphorylated Tau proteins generation, mediated partially by
      HSP90, HSP70 and HSP27 disruption, leading to cell death. These results provide
      new understanding of the mechanisms contributing to cadmium harmful effects on
      cholinergic neurons.

PMID- 30213553
TI  - Probabilistic cumulative dietary risk assessment of pesticide residues in foods
      for the German population based on food monitoring data from 2009 to 2014.
AB  - Cumulative dietary risks for the German population owing to pesticide residues in
      foods were assessed using food monitoring and consumption data. Based on grouping
      principles for cumulative assessment groups (CAG) as defined by the European Food
      Safety Authority, probabilistic modelling gave cumulative long- and short-term
      dietary exposures relevant to the nervous and thyroid system. Compound specific
      toxicological reference values were considered to assess the total margins of
      exposure (MoEs) for each CAG, allowing an assessment of the cumulative dietary
      consumer risk. For the German population, no public health concerns were
      identified for 6 of 11 CAGs. For three CAGs high uncertainties remained, since
      MoEs were less than the usually required threshold of 100 for the upper
      confidence interval of the modelling uncertainty. For two CAGs relevant to the
      nervous and thyroid system, possible health risks cannot be excluded with the
      selected approach. Most potent risk drivers were chlorpyrifos and the group of
      dithiocarbamates (expressed as propineb). For regulatory decisions on possible
      cumulative dietary health risks the limitations of the published approaches and
      the absence of harmonized data sources for robust refinements have to be
      considered. Future research to reduce this high uncertainty is considered
      necessary in this area.

PMID- 30213554
TI  - Skin irritation and sensitization potential of oxidative hair dye substances
      evaluated with in vitro, in chemico and in silico test methods.
AB  - Permanent oxidative hair dyes are widely used but their toxicity is not well
      established. Here we aimed to evaluate the skin sensitization and irritation of
      nine hair dye substances (MAP, MRP-N, RS, PAOX, 2,4-DAPE, 2,6-PYR, PPD, Grey HED
      and PM) permitted for use in EU and Korea, using in vitro and in chemico and in
      silico test methods. Skin sensitization was evaluated by the KeratinoSensTM
      assay, Direct Peptide Reactivity Assay (DPRA) and DEREK. Six of nine dyes tested
      were determined as sensitizers in common. However, the decision for MAP, RS or
      PAOX was diverged across assays showing 2 positives and 1 negative. Skin
      irritation of hair dye substances was assessed with or without 6% H2O2 on a
      reconstructed human epidermis, EpidermTM, which demonstrated that H2O2 increased
      the skin irritation potential of some hair dyes. PPD and PM were determined to be
      irritants with H2O2. Epidermal damages by hair dye and H2O2 could be further
      confirmed through the histology of tissue remaining after MTT assay.
      Collectively, our study demonstrated that hair dyes possess potential skin
      sensitization and irritation issues which could be further aggravated by H2O2.

PMID- 30213556
TI  - Identifying health information technology related safety event reports from
      patient safety event report databases.
AB  - OBJECTIVE: The objective of this paper was to identify health information
      technology (HIT) related events from patient safety event (PSE) report free-text
      descriptions. A difference-based scoring approach was used to prioritize and
      select model features. A feature-constraint model was developed and evaluated to
      support the analysis of PSE reports. METHODS: 5287 PSE reports manually coded as
      likely or unlikely related to HIT were used to train unigram, bigram, and
      combined unigram-bigram logistic regression and support vector machine models
      using five-fold cross validation. A difference-based scoring approach was used to
      prioritize and select unigram and bigram features by their relative importance to
      likely and unlikely HIT reports. A held-out set of 2000 manually coded reports
      were used for testing. RESULTS: Unigram models tended to perform better than
      bigram and combined models. A 300-unigram logistic regression had comparable
      classification performance to a 4030-unigram SVM model but with a faster relative
      run-time. The 300-unigram logistic regression model evaluated with the testing
      data had an AUC of 0.931 and a F1-score of 0.765. DISCUSSION: A difference-based
      scoring, prioritization, and feature selection approach can be used to generate
      simplified models with high performance. A feature-constraint model may be more
      easily shared across healthcare organizations seeking to analyze their respective
      datasets and customized for local variations in PSE reporting practices.
      CONCLUSION: The feature-constraint model provides a method to identify HIT
      related patient safety hazards using a method that is applicable across
      healthcare systems with variability in their PSE report structures.

PMID- 30213557
TI  - CAD/CAM milled removable complete dentures: time and cost estimation study.
AB  - ObjectiveThis study compared the clinical time spent and the costs incurred
      whilstconstructing complete dentures (CDs) using a two-visit digital-denture
      protocol (DDP) with the conventional complete denture protocol (CCDP), in a
      university setting.Methods Twelve undergraduate final-year dental students
      utilized both the DDP and the CCDP to construct two sets of CDs for patients
      requiring either an upper CD opposing a partial natural dentition restored using
      a partial removable prosthesis [Group#1: students: n = 6, upper CD: n = 12 (6-DDP
      +6-CCDP)] or both upper and lower CDs [Group#2: students: n = 6, upper and lower
      CDs: n = 24 (12-DDP + 12-CCDP)]. Overall time spent and costs (clinical,
      materials, and laboratory) were calculated. Cost minimization analyses was
      performed to compare the economic costs of the two protocols. Paired t-tests were
      applied for the statistical analyses (p < 0.05). Results CCDP required longer
      clinical time than DDP for both Group#1 (p = 0.0206) and Group#2 (p = 0.0020).
      The materials costs were higher for the DDP in both groups (Group#1 p < 0.0001;
      Group#2: p = 0.0002). The overall costs, were significantly higher for the CCDP
      than the DDP (Group#1: p = 0.0032;Group 2: p = 0.0080).ConclusionsIn a university
      setting student clinic in Geneva, Switzerland,construction of CDs utilizing a DDP
      is significantly less costly in terms of the chairside time and overall costs
      incurred when compared with the CCDP.

PMID- 30213555
TI  - Expression of STING Is Increased in Liver Tissues From Patients With NAFLD and
      Promotes Macrophage-Mediated Hepatic Inflammation and Fibrosis in Mice.
AB  - BACKGROUND & AIMS: Transmembrane protein 173 (TMEM173 or STING) signaling by
      macrophage activates the type I interferon-mediated innate immune response. The
      innate immune response contributes to hepatic steatosis and non-alcoholic fatty
      liver disease (NAFLD). We investigated whether STING regulates diet-induced in
      hepatic steatosis, inflammation, and liver fibrosis in mice. METHODS: Mice with
      disruption of Tmem173 (STINGgt) on a C57BL/6J background, mice without disruption
      of this gene (controls), and mice with disruption of Tmem173 only in myeloid
      cells were fed a standard chow diet, a high-fat diet (HFD; 60% fat calories), or
      a methionine- and choline-deficient diet (MCD). Liver tissues were collected and
      analyzed by histology and immunohistochemistry. Bone marrow cells were isolated
      from mice, differentiated into macrophages, and incubated with 5,6
      dimethylxanthenone-4-acetic acid (DMXAA; an activator of STING) or cyclic
      guanosine monophosphate-adenosine monophosphate (cGAMP). Macrophages or their
      media were applied to mouse hepatocytes or human hepatic stellate cells (LX2)
      cells, which were analyzed for cytokine expression, protein phosphorylation, and
      fat deposition (by oil red O staining after incubation with palmitate). We
      obtained liver tissues from patients with and without NAFLD and analyzed these by
      immunohistochemistry. RESULTS: Non-parenchymal cells of liver tissues from
      patients with NAFLD had higher levels of STING than cells of liver tissues from
      patients without NAFLD. STINGgt mice and mice with disruption only in myeloid
      cells developed less severe hepatic steatosis, inflammation, and/or fibrosis
      after the HFD or MCD than control mice. Levels of phosphorylated c-Jun N-terminal
      kinase and p65 and mRNAs encoding tumor necrosis factor and interleukins 1B and 6
      (markers of inflammation) were significantly lower in liver tissues from STINGgt
      mice vs control mice after the HFD or MCD. Transplantation of bone marrow cells
      from control mice to STINGgt mice restored the severity of steatosis and
      inflammation after the HFD. Macrophages from control, but not STINGgt, mice
      increased markers of inflammation in response to lipopolysaccharide and cGAMP.
      Hepatocytes and stellate cells cocultured with STINGgt macrophages in the
      presence of DMXAA or incubated with the medium collected from these macrophages
      had decreased fat deposition and markers of inflammation compared with
      hepatocytes or stellate cells incubated with control macrophages. CONCLUSIONS:
      Levels of STING were increased in liver tissues from patients with NAFLD and mice
      with HFD-induced steatosis. In mice, loss of STING from macrophages decreased the
      severity of liver fibrosis and the inflammatory response. STING might be a
      therapeutic target for NAFLD.

PMID- 30213558
TI  - Dietary oleic acid-induced CD36 promotes cervical cancer cell growth and
      metastasis via up-regulation Src/ERK pathway.
AB  - Epidemiological and experimental studies have revealed strong associations
      between dietary lipids and cancer risk. However, the molecular mechanisms
      underlying the effects of dietary fatty acids on the genesis and progression of
      cancer have been poorly explored. In this study, we found that a high olive oil
      diet stimulated cervical cancer (CC) carcinogenesis, and oleic acid (OA), the
      main lipid in olive oil, was associated with increased malignancy in HeLa cells.
      OA up-regulated the expression of CD36, which is the best characterized fatty
      acid transporter. Inhibiting CD36 prevented the tumor-promoting effects of OA,
      while overexpressing CD36 mimicked the effects of OA. Clinically, CD36 expression
      was positively correlated with tumor progression and poor prognosis in patients
      with CC. Furthermore, OA induced Src kinase and downstream ERK1/2 pathway
      activation in a CD36-dependent manner. Pretreatment of HeLa cells with an Src
      kinase inhibitor largely blocked the tumor-promoting effect of OA. Our findings
      suggest that dietary OA exerts a stimulatory effect on CC growth and metastasis,
      and CD36 might be a promising therapeutic target that acts against CC through an
      Src/ERK-dependent signaling pathway.

PMID- 30213559
TI  - ISG15 in cancer: Beyond ubiquitin-like protein.
AB  - ISG15, the product of interferon (IFN)-stimulated gene 15, is the first
      identified ubiquitin-like protein (Ubl), playing roles not only as an
      unconjugated form but also as a covalently conjugated form onto a target protein.
      ISG15 is not present in lower eukaryotes such as yeast, nematode
      (Caenorhabditis), or insect (Drosophila), indicating that the functions of ISG15
      and ISG15 conjugation (ISGylation) are restricted to higher eukaryotes and have
      evolved with IFN signaling. Despite the highlighted complexity of ISG15 and
      ISGylation, increasing evidences have been emerging that ISG15 and ISGylation are
      implicated in a variety of pivotal cellular processes, involving protein
      translation, autophagy, exosome secretion, DNA repair, and immune modulation,
      which emphasizes the necessity of re-evaluation of ISG15 and ISGylation. In this
      review, we highlight current knowledge in the molecular understanding and
      physiological relevance of ISG15 and ISGylation and discuss new insights into how
      ISG15 is implicated in the pathogenesis of cancer, which could contribute to
      therapeutic intervention in cancer.

PMID- 30213560
TI  - Pre-malignant transformation by senescence evasion is prevented by the PERK and
      ATF6alpha branches of the Unfolded Protein Response.
AB  - The incidence of carcinomas highly increases with age. However, the initial steps
      of the age-related molecular carcinogenic processes remain poorly characterized.
      We previously showed that normal human epidermal keratinocytes spontaneously and
      systematically escape from senescence to give rise to preneoplastic emerging
      cells through a process called post-senescence neoplastic emergence (PSNE). To
      identify molecular pathways involved in the switch from senescence to pre
      transformation, we performed Connectivity Map analyses and DAVID functional
      annotations followed by hierarchical clustering and multidimensional scaling of
      the gene expression signature of PSNE cells. We identified endoplasmic reticulum
      stress related pathways as key regulators of PSNE. Invalidation by RNA
      interference of the UPR sensors PERK, ATF6alpha, but not IRE1alpha, delayed the
      occurrence of senescence when performed in pre-senescent cells, and increased the
      PSNE frequency when performed in already senescent cells. Conversely, endoplasmic
      reticulum stress inducers applied to already senescent cells decreased the
      frequency of PSNE. In conclusion, these results indicate that the activation of
      the UPR could protect from the early carcinogenic steps by senescence evasion.
      This opens new avenues to explore therapeutics that could be useful in decreasing
      the age-associated tumor incidence.

PMID- 30213561
TI  - Mid term functional results following surgical treatment of recto-urinary
      fistulas postprostate cancer treatment.
AB  - INTRODUCTION: To evaluate the mid term functional results of patients treated for
      RUF and to determine an optimal treatment strategy to improve their quality of
      life. Recto-urinary Fistula (RUF) is a rare complication following prostate
      cancer treatment, and can have a major impact on patients' quality of life. There
      is a lack of consensus concerning the best approach and different techniques have
      been proposed: endoscopic, transrectal, perineal and transperitoneal (open,
      laparoscopic or robotic). MATERIALS AND METHODS: We retrospectively reviewed the
      charts of patients who underwent RUF repair from January 2001 to December 2010 at
      our Institute. 16 patients who developed RUF following prostate cancer treatment
      were included in the study. The fistula had to be confirmed both clinically and
      by imaging. All patients had follow up consultation every 3 month for the first
      year and then annually. They were asked to fill questionnaires evaluating
      functional outcomes. The International Continence Society (ICS) score was used to
      assess the postoperative urinary continence. Fecal continence was evaluated with
      the Wexner score and sexual function was assessed with the International Index
      for erectile function (IIEF-5) score. RESULTS: Eighty-seven percent patients
      (14/16) in our series developed RUF as a consequence of prostate cancer surgery
      and 13% (2/16) postbrachytherapy (BT). All patients initially had a diversion
      colostomy and a supra pubic catheter. 69% (11/16) underwent primary YM repair and
      73% (8/11) were successful. 2/3 primary failures were successfully retreated with
      graciloplasty. Primary gracilis flap interposition (GFI), on 3 non-irradiated
      patients were successful (100%). Primary GFI postbrachytherapy, no patient had
      recover urinary and digestive continuity. In total primary GIF was successful in
      60% (3/5). Over all long term, success rate with a urinary and digestive
      continuity and without recurrence of the fistula was 81% (13/16). Mid term
      functional results were evaluated at mean follow up of 40 months (14-92). 13%
      (2/16) achieved complete urinary continence, 48% (7/16) required single pad, 25%
      (4/16) developed major incontinence, 7% (1/16) required urinary diversion and 13%
      (2/16) developed complete urethral closure post BT requiring permanent suprapubic
      catheterization. Colostomy was reversed in 93% (15/16) cases. 75% (12/16)
      achieved complete faecal continence, minor incontinence (wexner score 3-4) was
      seen in 13% (2/16) and major incontinence (wexner score 14) in 7% (1/16) and 7%
      (1/16) required a long term colostomy. 19% (3/16) developed colostomy related
      complications. Only 13% (2/16) achieved adequate erections with the use of intra
      cavernosal prostaglandin injections. CONCLUSIONS: RUF following prostate cancer
      treatment is a serious complication with severe repercussion on patients' quality
      of life. Surgical repair with the York Mason technique or Gracilis Flap
      interposition is associated with good success rates. If available pediculed
      gracilis muscle should be used as it offers better success rates. LEVEL OF
      EVIDENCE: 3.

PMID- 30213562
TI  - Comparison of two simple models for prediction of short term mortality in
      patients after severe traumatic brain injury.
AB  - INTRODUCTION: The subscale motor score of Glasgow Coma Scale (msGCS) and the
      Abbreviated Injury Score of head region (HAIS) are validated prognostic factors
      in traumatic brain injury (TBI). The aim was to compare the prognostic
      performance of a HAIS-based prediction model including HAIS, pupil reactivity and
      age, and the reference prediction model including msGCS in emergency department
      (ED), pupil reactivity and age. METHODS: Secondary analysis of a prospective
      epidemiological study including patients after severe TBI (HAIS > 3) with follow
      up from the time of accident until 14 days or earlier death was performed in
      Switzerland. Performance of prediction, based on accuracy of discrimination [area
      under the receiver-operating curve (AUROC)], calibration (Hosmer-Lemeshow test)
      and validity (bootstrapping with 2000 repetitions to correct) for optimism of the
      two prediction models were investigated. A non-inferiority approach was performed
      and an a priori threshold for important differences was established. RESULTS: The
      cohort included 808 patients [median age 56 {inter-quartile range (IQR) 33-71},
      median motor part of GCS in ED 1 (1-6), abnormal pupil reactivity 29.0%] with a
      death rate of 29.7% at 14 days. The accuracy of discrimination was similar (AUROC
      HAIS-based prediction model: 0.839; AUROC msGCS-based prediction model: 0.826,
      difference of the 2 AUROC 0.013 (-0.007 to 0.037). A similar calibration was
      observed (Hosmer-Lemeshow X2 11.64, p = 0.168 vs. Hosmer-Lemeshow X2 8.66, p =
      0.372). Internal validity of HAIS-based prediction model was high (optimism
      corrected AUROC: 0.837). CONCLUSIONS: Performance of prediction for short-term
      mortality after severe TBI with HAIS-based prediction model was non-inferior to
      reference prediction model using msGCS as predictor.

PMID- 30213563
TI  - Liraglutide and cardiovascular outcomes in a real world type 2 diabetes cohort.
AB  - In the last years, due to new regulatory guidelines requiring a stringent
      documentation of cardiovascular (CV) safety of novel drugs for type 2 diabetes,
      cardiovascular outcomes safety trials (CVOTs) are requested. CVOTs increase the
      knowledge about the safety profile of the new drugs, but they have intrinsic
      limits that make difficult their transferability to clinical practice. For this
      reason, real world evidence is considered an important complement to experimental
      data. Among the glucagon-like peptide-1 receptor agonists, liraglutide in the
      LEADER CVOT demonstrated superiority in reducing the risk of major CV events
      (MACEs) vs. placebo. We conducted an observational, retrospective, longitudinal
      study based on 307 patients with T2DM treated with liraglutide under routine
      clinical practice conditions. Real world impact of liraglutide on metabolic
      control, CV risk factors, hypoglycemia and CV events was assessed. Improvements
      during 36 months were found in HbA1c (-1.0%; p < 0.0001), fasting blood glucose (
      17.6 mg/dL; p < 0.0001), body weight (-3.2 kg; p < 0.0001), waist circumference (
      1.45 cm; p = 0.004), systolic blood pressure (-10.41 mmHg; p < 0.0001), diastolic
      blood pressure (-3.69 mmHg; p < 0.0001), total cholesterol (-7.96 mg/dL; p
      =0.008) and triglycerides (-20.60 mg/dl; p = 0.01). No severe hypoglycemia
      occurred. Incidence of MACEs in this cohort was lower than in the LEADER study
      (2.59 vs. 3.4 events per 100 person-years), confirming CV safety of liraglutide
      even in the real world. On the other hand, a higher incidence of CV event in
      patients with established CV disease was documented (8.1 events per 100 person
      years), in spite of the use of liraglutide. In conclusion, 36-month durability
      and CV safety of liraglutide were documented in a real world cohort of T2DM
      patients, with sustained benefits on a large array of CV risk factors.

PMID- 30213564
TI  - Clinical utility of ABCB1 genotyping for preventing toxicity in treatment with
      irinotecan.
AB  - Preventing severe irinotecan-induced adverse reactions would allow us to offer
      better treatment and improve patients' quality of life. Transporters,
      metabolizing enzymes, and genes involved in the folate pathway have been
      associated with irinotecan-induced toxicity. We analyzed 12 polymorphisms in
      UGT1A1, ABCB1, ABCG2, ABCC4, ABCC5, and MTHFR in 158 patients with metastatic
      colorectal cancer treated with irinotecan and studied the association with grade
      >2 adverse reactions (CTCAE). Among the most frequent ADRs, the SNPs rs1128503,
      rs2032582, and rs1045642 in ABCB1 and rs1801133 in MTHFR were associated with
      hematological toxicity and overall toxicity. The SNP rs11568678 in ABCC4 was also
      associated with overall toxicity. After correction of P values using a false
      discovery rate, only ABCB1 variants remained statistically significant. Haplotype
      analysis in ABCB1 showed an 11.3-fold and 4.6-fold increased risk of
      hematological toxicity (95% CI, 1.459-88.622) and overall toxicity (95% CI, 2.283
      9.386), respectively. Consequently, genotyping of the three SNPs in ABCB1 can
      predict overall toxicity and hematological toxicity with a diagnostic odds ratio
      of 4.40 and 9.94, respectively. Genotyping of ABCB1 variants can help to prevent
      severe adverse reactions to irinotecan-based treatments in colorectal cancer.

PMID- 30213565
TI  - Crystal anisotropy explains structure-mechanics impact on tableting performance
      of flufenamic acid polymorphs.
AB  - Anisotropic features with other crystallographic properties like d-spacing, and
      attachment energy (Eatt) can predict material performance during the secondary
      pharmaceutical processing. A newly developed state-of-the-art compression cell
      lodged in a powder X-ray diffractometer was used to measure anisotropic Young's
      moduli (YM) of flufenamic acid (FFA) polymorphs in this study. Methodology is
      based on the generation of a single crystal deformation in this cell, which
      reflects as a change in the d-spacing in the PXRD pattern. Anisotropic YM was
      calculated from such information gathered along different FFA planes. Measured
      FFA crystallographic molecular features were concatenated to understand
      macroscopic compaction (Heckel and Shapirao's parameters) and tableting
      performance. Block shaped crystals of FFA form I, and III after initial
      characterization with SEM, DSC, PXRD, and FTIR were compressed normal to X, Y,
      and Z-planes, identified from calculated PXRD pattern using the reported single
      crystal structure. YM of X and Y planes of form I was significantly higher than
      corresponding planes of form III. Z plane of form III showed significantly higher
      YM than that for form I. Low YM of form III can be attributed to its large d
      spacing regardless of their high Eatt than form I, as well as orientation of
      supramolecular acid dimer (OH?O) homosynthon chains in the FFA planes. FFA form I
      stiffness was further confirmed with lower densification and higher yield
      pressure of deformation than form III. Clearly, form III exhibited better
      compressibility, compactibility, and tableting performance than form I due to
      favorable molecular and macroscopic features. Thus, developed anisotropic
      measurement approach can be used to distinguish material performance in the early
      development stage of the pharmaceutical processes.

PMID- 30213566
TI  - The future of drug development: the paradigm shift towards systems therapeutics.
AB  - Progress in cell biology, genetics, molecular, and systems pharmacology is the
      driving force behind a current paradigm shift in drug research. This paradigm
      shift shapes new avenues for advanced treatments that are commonly referred to as
      'systems therapeutics'. Systems therapeutics differ in many ways from current
      drugs because they target biological networks rather than single transduction
      pathways, and affect disease processes rather than physiological processes. Here,
      we examine how the paradigm shift towards systems therapeutics will change
      current scientific concepts of the interactions between drugs and diseases, the
      organization of research and development, as well as the clinical use and
      therapeutic evaluations of therapeutic interventions.

PMID- 30213567
TI  - Do urocortins have a role in treating cardiovascular disease?
AB  - Corticotropin-releasing factor (CRF) and the three homolog neuropeptides,
      urocortin (UCN) 1, 2 and 3, are the major neuroendocrine factors implicated in
      the response of the body to stress. Recent evidence suggests that UCNs have a
      significant role in the pathogenesis and management of cardiovascular disease,
      such as congestive heart failure, ischemic heart disease, and hypertension. These
      data led to the initiation of clinical trials testing a possible role of UCNs in
      the diagnosis and therapy of cardiovascular disease, with encouraging results.
      Here, we summarize the available literature concerning the role of UCNs in the
      cardiovascular system, focusing on the emerging data creating a potential for
      clinical applications.

PMID- 30213568
TI  - Characterization of biological pathways associated with semen traits in the Thai
      multibreed dairy population.
AB  - The objective of this research was to characterize biological pathways associated
      with semen volume (VOL), number of sperm (NS), and sperm motility (MOT) of dairy
      bulls in the Thai multibreed dairy population. Phenotypes for VOL (n = 13,535),
      NS (n = 12,773), and MOT (n = 12,660) came from 131 bulls of the Dairy Farming
      Promotion Organization of Thailand. Genotypic data consisted of 76,519 imputed
      and actual single nucleotide polymorphisms (SNP) from 72 animals. The SNP
      variances for VOL, NS, and MOT were estimated using a three-trait genomic
      polygenic repeatability model. Fixed effects were contemporary group, ejaculate
      order, age of bull, ambient temperature, and heterosis. Random effects were
      animal additive genetic, permanent environmental, and residual. Individual SNP
      explaining at least 0.001% of the total genetic variance for each trait were
      selected to identify associated genes in the NCBI database (UMD Bos taurus 3.1
      assembly) using the R package Map2NCBI. A set of 1,999 NCBI genes associated with
      all three semen traits was utilized for the pathway analysis conducted with the
      ClueGO plugin of Cytoscape using information from the Kyoto Encyclopedia of Genes
      and Genomes database. The pathway analysis revealed seven significant biological
      pathways involving 127 genes that explained 1.04% of the genetic variance for
      VOL, NS, and MOT. These genes were known to affect cell structure, motility,
      migration, proliferation, differentiation, survival, apoptosis, signal
      transduction, oxytocin release, calcium channel, neural development, and immune
      system functions related to sperm morphology and physiology during
      spermatogenesis.

PMID- 30213569
TI  - Nerve Growth Factor-beta production in the bull: Gene expression,
      immunolocalization, seminal plasma constitution, and association with sire
      conception rates.
AB  - Nerve Growth Factor-beta (NGF) is a seminal plasma protein that regulates sperm
      physiology in bulls, yet its production and association with fertility remain
      unclear. The objective of this study was to describe NGF distribution in bull
      accessory sex glands, quantify its seminal plasma concentrations, and determine
      its association with sire conception rates. Accessory sex glands were collected
      post-mortem from mature bulls (n = 3). Quantitative PCR and immunohistochemistry
      were performed in tissue samples. Pre-ejaculate and sperm-rich fraction of
      seminal plasma from Angus (n = 42) and sperm-rich fraction from Holstein (n = 10)
      bulls were collected by electroejaculation. Holstein (n = 76) and Jersey (n = 14)
      bulls were collected by artificial vagina, and those with available sire
      conception rate scores were allocated to: (1) negative/0 (n = 15); or (2)
      positive (n = 45). Seminal plasma NGF concentrations were measured using ELISA.
      Relative abundance of NGF mRNA was greatest in the vesicular, intermediate in
      ampulla, and lowest in prostate and bulbourethral glands (P <= 0.03). The most
      intense NGF staining was detected in the ampulla and vesicular glands (P < 0.05).
      Concentrations of NGF were greater in the sperm-rich fraction than in the pre
      ejaculate and in samples collected by artificial vagina (P < 0.01). Seminal
      plasma NGF concentrations were greater in bulls with positive sire conception
      rate than those with negative/0 (P = 0.05). This study determined that NGF is
      produced in the ampulla and vesicular glands of bulls and is secreted into the
      sperm-rich fraction of the ejaculate. The positive association of NGF with bull
      fertility warrants further investigation.

PMID- 30213570
TI  - Effects of maternal feed intake restriction during pregnancy on the expression of
      growth regulation, imprinting and epigenetic transcription-related genes in
      foetal goats.
AB  - Maternal nutrition during gestation is a leading factor of modifying the foetal
      epigenome and phenotype for mammals. Imprinting genes have important roles in
      regulating foetal growth, programming and development. There, however, are
      limited data available on the effects of feed intake restriction on the
      expression of imprinting genes in pregnant goats. The present study, therefore,
      was conducted to assess the effects of maternal feed intake restriction on the
      relative abundance of mRNA for growth imprinting, DNA methyltransferase (DNMT)
      and epigenetic transcription-related genes in the liver and heart of foetal goats
      during gestation. A total of 24 Liuyang black goats (2.0+/-0.3 yr) with similar
      body weight (BW, 31.22+/-8.09 kg) and parity (2) were allocated equally to either
      a control group (CG) or a restriction group (RG) during both early (from 26 to 65
      days) and late (from 96 to 135 days) gestation. All goats were fed a mixed diet
      and had free access to fresh water. The feed of the RG was 40% less than that of
      the CG. The early and late gestation goats were weighed, bled and slaughtered on
      days 65 and 135 of gestation, respectively. In early gestation, the foetal
      weight, body length, the weight of foetal heart and liver were greater (P < 
      0.05) in the RG. The CpG methylation of genomic DNA in the foetal heart was less
      (P =  0.0001) in the RG. The relative abundance of mRNA of methyl-CpG-binding
      domain protein 2 (MBD2) and methyl-CpG-binding domain protein 3 (MBD3) genes in
      the foetal liver were greater (P <  0.05) in the RG. During the late gestation,
      the foetal weight, heart weight and liver weight were less (P <  0.05) in the RG.
      The relative abundance of mRNA for the MBD2 gene (P =  0.043) in the foetal
      heart, and the ten-eleven translocation protein 1 (TET1) gene (P <  0.05) in both
      the foetal heart and liver were greater in the RG. These results indicate feed
      intake restriction during gestation influenced foetal development and regulated
      the relative abundance of mRNA for epigenetic transcription-related genes.

PMID- 30213571
TI  - TGF-beta4 and HSP70 responses in breeder hens treated with thyroxine.
AB  - A hypothesis was tested that long-term administration of thyroxine (T4) in
      broiler breeder hens would affect fertility, sperm penetration rate, and the
      duration of fertility. Relative abundance of oviductal TGF-beta4 and HSP70 mRNA
      was determined to ascertain whether T4 treatment affected these genes, and
      modulated the sustained storage of spermatozoa within the uterovaginal sperm
      storage tubules of hens. A total of 70, 47-week-old Cobb 500 breeder hens was
      randomly allotted to two treatment groups (T4 treatment (ET) and control). The T4
      was orally administered to the ET group (0.3 mg T4/bird/day) for 100 consecutive
      days; whereas the control group was not administered T4 during the experimental
      period. Breeder hens were artificially inseminated to evaluate specific
      reproductive variables. On the last day of the treatment period two hens
      /replicate were randomly killed to estimate oviductal gene expression. The T4
      treatment resulted in an increase in plasma concentration of T4; however, the T3
      concentration was not affected. The long term administration of T4 had no effect
      on fertility; however, it resulted in a decreased sperm penetration rate and
      decreased the duration of fertility compared with the control group. The relative
      abundance of TGF-beta4 and HSP70 mRNA in the SST was not influenced by T4
      supplementation. The correlation coefficients between fertility and sperm
      penetration rate with relative abundance of TGF-beta4 and HSP70 were not
      significant. Overall, among the diverse reproductive variable assessed in the
      current study, the sperm penetration rate and the duration of fertility were most
      responsive to long-term treatment with T4.

PMID- 30213572
TI  - Physico-mechanical and antimicrobial properties of tragacanth/hydroxypropyl
      methylcellulose/beeswax edible films reinforced with silver nanoparticles.
AB  - The novel trinary bio-composite film based on Tragacanth/Hydroxypropyl
      methylcellulose/Beeswax reinforced silver nanoparticles (AgNPs) was developed.
      This study investigated the effect of AgNPs (2, 4 and 8%) on some physico
      mechanical and antimicrobial properties of bio-composite film. It was discovered
      that AgNPs reduced the composite tensile strength from 33.64 to 16.12 MPa.
      However, water vapor permeability was improved by addition of the nanoparticles
      (4.57-2.16 * 10-13 g m/m2 s Pa). The use of AgNPs influenced the apparent color
      of bio-composite film. The microscopic surface structure and topography of the
      films were also examined by scanning electron microscopy and Fourier transform
      infrared, respectively. Dynamic mechanical thermal analysis results showed that
      the thermal stability of film was slightly decreased through incorporation with
      AgNPs. Finally, nano-composite films demonstrated strong antibacterial activity
      against tested pathogen bacteria in the contact surface zone. The antimicrobial
      results suggest that new nanocomposite film may be used as food active packaging.

PMID- 30213573
TI  - Management of antenatally detected kidney malformations.
AB  - Congenital anomalies of the kidneys and the urinary tract (CAKUT) are one of the
      most common sonographically identified antenatal malformations. Dilatation of the
      renal pelvis accounts for the majority of cases, but this is usually mild rather
      than an indicator of obstructive uropathy. Other conditions such as small through
      large hyperechogenic and/or cystic kidneys present a significant diagnostic
      dilemma on routine scanning. Accurate diagnosis and prediction of prognosis is
      often not possible without a positive family history, although maintenance of
      adequate amniotic fluid is usually a good sign. Both pre- and postnatal genetic
      screening is possible for multiple known CAKUT genes but less than a fifth of non
      syndromic sporadic cases have detectable monogenic mutations with current
      technology. In utero management options are limited, with little evidence of
      benefit from shunting of obstructed systems or installation of artificial
      amniotic fluid. Often outcome hinges on associated cardiac, neurological or other
      abnormalities, particularly in syndromic cases. Hence, management centres on a
      careful assessment of all anomalies and planning for postnatal care. Early
      delivery is rarely indicated since this exposes the baby to the risks of
      prematurity in addition to their underlying CAKUT. Parents value discussions with
      a multidisciplinary team including fetal medicine and paediatric nephrology or
      urology, with neonatologists to plan perinatal care and clinical geneticists for
      future risks of CAKUT.

PMID- 30213574
TI  - INR Control of Patients with Mechanical Heart Valve on Long-Term Warfarin
      Therapy.
AB  - BACKGROUND: Warfarin is an anticoagulant indicated for patients who had undergone
      mechanical heart valve(s) replacement (MHVR). In these patients, time in
      therapeutic range (TTR) is important in predicting the bleeding and thrombotic
      risks. OBJECTIVE: This study aimed to describe the anticoagulation control of
      warfarin using TTR in patients with MHVR in a tertiary health care referral
      Center. METHODS: Data were collected retrospectively by reviewing clinical notes
      of outpatients who attended international normalized ratio (INR) clinics in
      November 2015. Patients who had MHVR and who took warfarin were included. The
      data collected were demographics, relevant laboratory investigations, and
      patients' prior medical history. TTR was calculated using Rosendaal and
      traditional methods. RESULTS: A total of 103 patients with MHVR were recruited.
      The mean age was 51.72 +/- 13.97 years and 46.6% were male. A total of 54.4% had
      mitral valve replacement (MVR), whereas 26.2% had aortic valve replacement (AVR).
      The mean TTR calculated using the Rosendaal method was 57.1%. There was no
      significant difference among patients with AVR, MVR, and both valves (AMVR) in
      terms of TTR (AVR vs. MVR vs. AMVR, 62.94 +/- 23.08, 54.12 +/- 21.62, 57.63 +/-
      17.47; p = 0.213). The average dose of warfarin for all groups was approximately
      3 mg/day. Moreover, MVR, AVR, and AMVR patients who had TTR (Rosendaal method)
      <=60% were 58.9%, 37.0%, and 45.0%, respectively. Only 4.8% had minor bleeding,
      whereas none had stroke in the period of TTR determination. CONCLUSIONS: Despite
      a majority of patients having <60% TTR, there were low incidences of bleeding and
      stroke events in this center. There were no factors found to be associated with
      INR control in this study.

PMID- 30213575
TI  - EUS-guided cholecystostomy versus endoscopic transpapillary cholecystostomy for
      acute cholecystitis in high-risk surgical patients.
AB  - BACKGROUND AND AIMS: Endoscopic gallbladder drainage (GBD) has been performed as
      an alternative to percutaneous drainage for acute cholecystitis. To date, there
      has been no comparative study between EUS-guided cholecystostomy (EUSC) and
      endoscopic transpapillary cholecystostomy (ETC). The aim of this study was to
      compare the outcomes of EUSC and ETC. METHODS: A retrospective review of an
      endoscopic GBD database prospectively collected at the Asan Medical Center
      (between July 2010 and December 2014) was performed to identify consecutive
      patients with acute cholecystitis who underwent attempted endoscopic GBD.
      Procedural and long-term outcomes were evaluated using inverse probability of
      treatment weighting (IPTW). RESULTS: A total of 172 patients (76 in the EUSC
      group and 96 in the ETC group) were included in this study. Seven patients who
      failed to undergo ETC crossed over to the EUSC group. After adjustment with the
      IPTW method, technical success (99.3% vs 86.6%, P < .01) and clinical success
      (99.3% vs 86%, P < .01) rates were significantly higher in the EUSC group than in
      the ETC group. The procedure-related adverse event rate was significantly higher
      in the ETC group (7.1% vs 19.3%, P = .02). The cholecystitis or cholangitis
      recurrence rate (12.4% vs 3.2%) was also higher in the ETC group than in the EUSC
      group, as identified using Cox analysis (hazard ratio, 3.01; 95% confidence
      interval, .73-12.9; P = .04). CONCLUSIONS: In patients with acute cholecystitis
      who are unfit for surgery, EUSC may be a more suitable treatment method than ETC.

PMID- 30213576
TI  - Critically appraised paper: The addition of exercise training to a weight-loss
      program improves clinical control in adults with asthma [synopsis].

PMID- 30213577
TI  - Critically appraised paper: Short-term preoperative exercise training improves
      exercise capacity and reduces postoperative pulmonary complications in people
      undergoing lung cancer surgery [synopsis].

PMID- 30213578
TI  - Critically appraised paper: Long-term, individualised physical activity and
      exercise coaching does not improve maintenance of motor function after stroke
      [commentary].

PMID- 30213579
TI  - Critically appraised paper: Workplace physical exercise reduces musculoskeletal
      pain among healthcare workers more than home-based exercise [commentary].

PMID- 30213580
TI  - Modulation of the monocyte/macrophage system in heart failure by targeting heme
      oxygenase-1.
AB  - Upon myocardial infarction (MI) immune system becomes activated by extensive
      necrosis of cardiomyocytes releasing intracellular molecules called damage
      associated molecular patterns. Overactive and prolonged immune responses are
      likely to be responsible for heart failure development and progression in
      patients surviving the ischemic episode. Heme oxygenase-1 (HO-1) plays a crucial
      role in heme degradation and in this way releases carbon monoxide, free iron, and
      biliverdin. This stress-inducible enzyme is induced by various oxidative and
      inflammatory signals. Consequently, biological actions of HO-1 are not limited to
      degradation of a toxic heme released from hemoproteins, but also provide an
      adaptive cellular response against chronic inflammation and oxidative injury.
      Indeed, the immunomodulatory and anti-inflammatory properties of HO-1 were
      demonstrated in several experimental studies, as well as in human cases of
      genetic HO-1 deficiency. HO-1 was shown to suppress the production, myocardial
      infiltration and inflammatory properties of monocytes and macrophages what
      resulted in limitation of post-MI cardiac damage. This review specifically
      addresses the role of HO-1, heme and its degradation products in macrophage
      biology and post-ischemic cardiac repair. A more complete understanding of these
      mechanisms is essential to develop new therapeutic approaches.

PMID- 30213581
TI  - Association Between Plasma Level of Collagen Type III alpha 1 Chain and
      Development of Strictures in Pediatric Patients With Crohn's Disease.
AB  - BACKGROUND & AIMS: There are few serum biomarkers to identify patients with
      Crohn's disease (CD) who are at risk for stricture development. The extracellular
      matrix components, collagen type III alpha 1 chain (COL3A1) and cartilage
      oligomeric matrix protein (COMP), could contribute to intestinal fibrosis. We
      investigated whether children with inflammatory CD (B1) who later develop
      strictures (B2) have increased plasma levels of COL3A1 or COMP at diagnosis,
      compared to children who remain B1. We compared results to previously studied
      biomarkers, including autoantibodies against colony stimulating factor 2 (CSF2).
      METHODS: We selected 161 subjects (mean age, 12.2 years; 62% male) from the Risk
      Stratification and Identification of Immunogenic and Microbial Markers of Rapid
      Disease Progression in Children with Crohn's cohort, completed at 28 sites in the
      United States and Canada from 2008 through 2012. The children underwent
      colonoscopy and upper endoscopy at diagnosis and were followed every 6 months for
      36 months; plasma samples were collected at baseline. Based on CD phenotype,
      children were separated to group 1 (B1 phenotype at diagnosis and follow up),
      group 2 (B2 phenotype at diagnosis), or group 3 (B1 phenotype at diagnosis who
      developed strictures during follow up). Plasma samples were collected from
      patients and 40 children without inflammatory bowel disease (controls) at
      baseline and analyzed by ELISA to measure COL3A1 and COMP. These results were
      compared with those from a previous biomarker study. Kruskal-Wallis test and
      pairwise Dunn's tests with Bonferroni correction were used to compare differences
      among groups. RESULTS: The median baseline concentration of COL3A1 was
      significantly higher in plasma from group 3 vs group 1 (P<.01) and controls
      (P=.01). Median baseline plasma concentrations of COMP did not differ
      significantly among groups. A model comprising baseline concentrations of COL3A1
      and anti-CSF2 identified patients with B2 vs B1 CD with an area under the curve
      of 0.80 (95% CI, 0.71-0.89); the combined concentration identified patients with
      strictures with a sensitivity value of 0.70 (95% CI, 0.55-0.83) and a specificity
      value of 0.83 (95% CI 0.67-0.93). CONCLUSION: We found median plasma
      concentrations of COL3A1, measured by ELISA at diagnosis, to be significantly
      higher in patients with CD who later developed strictures than in patients
      without strictures. The combination of concentrations of COL3A1 and anti-CSF2
      might be used to identify pediatric patients at CD diagnosis who are at risk for
      future strictures.

PMID- 30213582
TI  - Numbers and Features of Patients With a Diagnosis of Celiac Disease Without
      Duodenal Biopsy, Based on a National Survey.
AB  - BACKGROUND & AIMS: According to guidelines, individuals with symptoms of celiac
      disease should undergo duodenal biopsy analysis to establish a diagnosis, but
      little is known about physician adherence to these guidelines. We used a patient
      powered research network (PPRN) to compare demographics, diagnoses, symptoms, and
      treatment between groups of patients with celiac disease diagnosed by biopsy
      analysis and patients with a diagnosis based on results of serology tests.
      METHODS: We analyzed data from iCureCeliac-a voluntary, PPRN hosted and
      distributed by the Celiac Disease Foundation, from January 30, 2016, through
      August 25, 2016. We compared data from adults with a diagnosis of celiac disease
      (mean age, 43.4 years; 85.6% female) based on biopsy analysis (n = 780) vs
      patients with a diagnosis based on only serologic analysis (n = 202) using
      univariate and multivariable analyses. We collected demographic information, as
      well as data on type of health care practitioner, where patients obtain their
      primary information about celiac disease, and the Celiac Disease Quality of Life
      score, nutritionist referral rates, adherence to the gluten-free diet, ongoing
      symptoms and use of supplements. RESULTS: Among patients with a diagnosis based
      on serology results, 33.3% were diagnosed by non-gastroenterologists vs 20.7% in
      the biopsy diagnosed group (P < .001). Fewer patients with a diagnosis based on
      serology results sought nutritional counseling at the time of diagnosis (40.1%)
      than patients with a diagnosis based on biopsy (58.9%) (P < .001). A higher
      proportion of patients diagnosed by serology without biopsy took dietary
      supplements to aid in digestion of gluten (19.8%) than patients with a diagnosis
      based on biopsy (8.9%) (P < .001). After we adjusted for age and sex, patients
      with a diagnosis based on serology were less likely to seek nutritional
      counseling after diagnosis (odds ratio [OR], 0.45; 95% CI, 0.33-0.63), less
      likely to receive a diagnosis from a gastroenterologist (OR, 0.16; 95% CI, 0.07
      0.37), and more likely to use digestive supplements (OR, 2.61; 95%, CI 1.62
      4.19). CONCLUSIONS: In an analysis of data from a PPRN, we found that 21% of
      adult participants with celiac disease did not have a diagnosis based on a
      duodenal biopsy. Patients with a diagnosis based on serology results were more
      likely to be diagnosed by non-gastroenterologists, less likely to seek
      nutritional counseling, and more likely to use dietary supplements. Patients
      require more education about management of celiac disease and referral to
      gastroenterologists for duodenal biopsy confirmation of their disease.

PMID- 30213583
TI  - Clinical and Molecular Factors Associated With Histologic Response to Topical
      Steroid Treatment in Patients With Eosinophilic Esophagitis.
AB  - BACKGROUND & AIMS: Few factors have been identified that can be used to predict
      response of patients with eosinophilic esophagitis (EoE) to topical steroid
      treatment. We aimed to determine whether baseline clinical, endoscopic,
      histologic, and molecular features of EoE can be used to predict histologic
      response. METHODS: We collected data from 97 patients with EoE, from 2009 through
      2015, treated with a topical steroid for 8 weeks; 59 patients had a histologic
      response to treatment. Baseline clinicopathologic features and gene expression
      patterns were compared between patients with a histologic response to treatment
      (<15 eos/hpf) and non-responders (>=15 eos/hpf). We performed sensitivity
      analyses for alternative histologic response definitions. Multivariate logistic
      regression was performed to identify predictive factors associated with response
      to therapy, which were assessed with area under the receiver operator
      characteristic (AUROC) curves. RESULTS: Baseline dilation was the only
      independent predictor of non-response (odds ratio [OR], 0.30; 95% CI, 0.10-0.89).
      When an alternate response (<1 eos/hpf) and non-response (<50% decrease in
      baseline eos/hpf) definition was used, independent predictors of response status
      were age (OR, 1.08; 95% CI, 1.02-1.14), food allergies (OR, 12.95; 95% CI, 2.20
      76.15), baseline dilation (OR, 0.17; 95% CI, 0.03-0.88), edema or decreased
      vascularity (OR, 0.20; 95% CI, 0.04-1.03), and hiatal hernia (OR, 0.07; 95% CI,
      0.01-0.66). Using these 5 factors, we developed a predictive model that
      discriminated complete responders from non-responders with an AUROC of 0.88.
      Baseline gene expression patterns were not associated with treatment response and
      did not change with different histologic response thresholds. CONCLUSIONS: In an
      analysis of 97 patients with EoE, we found dilation to be the only baseline
      factor associated with non-response to steroid treatment (<15 eos/hpf). However,
      a model comprising 5 clinical, endoscopic, and histologic factors identified
      patients with a complete response (<1 eos/hpf). A baseline gene expression panel
      was not predictive of treatment response at any threshold.

PMID- 30213584
TI  - Efficacy and Safety of Induction Therapy With Calcineurin Inhibitors in
      Combination With Vedolizumab in Patients With Refractory Ulcerative Colitis.
AB  - BACKGROUND & AIMS: Vedolizumab is used to treat patients with ulcerative colitis
      (UC), although there is a delay before it is effective. Induction therapy with a
      calcineurin inhibitor (cyclosporine or tacrolimus) in combination with
      vedolizumab as maintenance therapy could be an option for patients with an active
      steroid-refractory UC. We assessed the efficacy and safety of this combination.
      METHODS: We performed a retrospective observational study, collecting data from
      12 referral centers in France that were included in the Groupe d'Etude
      Therapeutique des Affections Inflammatoires du tube Digestif. We collected
      information on 39 patients with an active steroid-refractory UC (31 with active
      severe UC and 36 failed by treatment with a tumor necrosis factor antagonist) who
      received a calcineurin inhibitor as induction therapy along with vedolizumab as
      maintenance therapy. Inclusion date was the first vedolizumab infusion. The
      outcomes were survival without colectomy, survival without vedolizumab
      discontinuation, and safety. RESULTS: After a median follow-up period of 11
      months, 11 patients (28%) underwent colectomy. At 12 months, 68% of the patients
      survived without colectomy (95% CI, 53%-84%) and 44% survived without vedolizumab
      discontinuation (95% CI, 27%-61%). No deaths occurred and 4 severe adverse events
      were observed. CONCLUSIONS: In a retrospective analysis of 39 patients with an
      active steroid-refractory UC (most refractory to a tumor necrosis factor
      antagonist), we found that initial treatment with a calcineurin inhibitor in
      combination with vedolizumab allowed more than two thirds of patients to avoid
      colectomy. Further studies are needed to assess the safety of this strategy.

PMID- 30213585
TI  - Cortico-anorectal, Spino-anorectal, and Cortico-spinal Nerve Conduction and Locus
      of Neuronal Injury in Patients With Fecal Incontinence.
AB  - BACKGROUND & AIMS: The neuropathophysiology of fecal incontinence (FI) is
      incompletely understood. We examined the efferent brain-anorectal and spino
      anorectal motor-evoked potentials (MEP) to characterize the locus of neuronal
      injury in patients with FI. METHODS: We performed bilateral transcranial,
      translumbar, and transsacral magnetic stimulations in 27 patients with FI (19
      female) and 31 healthy individuals (controls, 20 female) from 2015 through 2017.
      MEPs were recorded simultaneously from the rectum and anus using 4 ring
      electrodes. The difference in MEP latencies between the transcranial (TMS) and
      translumbar transsacral magnetic stimulations was calculated as cortico-spinal
      conduction time. MEP data were compared between patients with FI and controls.
      Patients filled out questionnaires that assessed the severity and effects of FI.
      RESULTS: The MEP latencies with TMS were significantly longer in patients with FI
      than controls at most sites, and on both sides (P < .05). Almost all translumbar
      and transsacral MEP latencies were significantly prolonged in patients with FI vs
      controls (P < .01). The cortico-spinal conduction time were similar, on both
      sides, between patients with FI and controls. Ninety-three percent of patients
      had 1 or more abnormal translumbar and transsacral latencies, but neuropathy was
      patchy and variable, and not associated with sex or anal sphincter function or
      defects. CONCLUSIONS: Patients with FI have significant neuropathy that affects
      the cortico-anorectal and spino-anorectal efferent pathways. The primary loci are
      the lumbo-rectal, lumbo-anal, sacro-rectal, and sacro-anal nerves; the cortico
      spinal segment appears intact. Peripheral spino-anal and spino-rectal neuropathy
      might therefore contribute to the pathogenesis of FI.

PMID- 30213586
TI  - Is Low Level Viremia Acceptable During Antiviral Therapy of Patients With HBV
      Infection and Decompensated Cirrhosis?

PMID- 30213587
TI  - Incidence of Progression of Persistent Nondysplastic Barrett's Esophagus to
      Malignancy.
AB  - BACKGROUND & AIMS: The risk of esophageal adenocarcinoma (EAC) in patients with
      non-dysplastic Barrett's esophagus (NDBE) is low, so there is debate over the
      role of ongoing surveillance for patients with NDBE. It is important to identify
      patients at low risk for progression. We assessed cancer risk based on the
      subsequent number of endoscopies showing persistence of NDBE in a nationwide
      study in the Netherlands. METHODS: In a population-based study, patients with a
      first diagnosis of NDBE were selected from the Dutch nationwide registry of
      histopathology. We calculated incidence rates and incidence rate ratios (IRR) for
      high-grade dysplasia (HGD) and EAC to determine whether the number of endoscopies
      negative for dysplasia and the persistence of NDBE over time associate with
      progression to malignancy. RESULTS: We identified 12,728 patients with NDBE
      during 2003 and 2013. HGD or EAC developed in 436 patients (3.4%) during 64,537
      person-years of follow up (median, 4.9 years). The rate of progression to HGD or
      EAC was 0.68 (95% CI, 0.61-0.74) per 100 person-years. In patients with 2
      consecutive endoscopies showing NDBE, the rate of progression to HGD or EAC
      decreased to 0.55 (95% CI, 0.46-0.64) per 100 person-years (IRR 0.72; 95% CI,
      0.60-0.87). Overall, the incidence of HGD or EAC decreased by 14% for each year
      of progression-free follow-up (IRR, 0.86; 95% CI, 0.81-0.92). CONCLUSION: In a
      population-based study in the Netherlands, we found patients with stable NDBE to
      have a low risk of progression to HGD or EAC. These findings indicate that
      surveillance intervals might be lengthened or even discontinued in subgroups
      patients with persistent NDBE.

PMID- 30213588
TI  - Prehospital clinical presentation in patients with acute coronary syndrome
      complicated by cardiogenic shock: A single center study.
AB  - BACKGROUND: The development of cardiogenic shock remains the most important
      factor affecting the prognosis of patients with acute coronary syndrome. Despite
      significant advances in treatment, achieved in the last two decades, the
      mortality rate is still very high. The development of knowledge about the
      pathophysiology of cardiogenic shock, necessitates a thorough and comprehensive
      assessment of its progress at all stages of medical care. OBJECTIVES: The aim of
      the study was to assess the prehospital clinical presentation in patients with
      acute coronary syndrome complicated by cardiogenic shock. METHODS: The population
      of our study consisted of 40 patients with acute coronary syndrome complicated by
      cardiogenic shock who were transported to the Intensive Cardiac Therapy Clinic by
      ambulances directly from place of the event in order to implement primary
      coronary intervention. The control group was selected among age, gender and
      infarct location-matched patients with acute coronary syndrome uncomplicated by
      shock. The clinical presentation in investigated patients was assessed on the
      basis of the data contained in the medical records of Emergency Medical Services
      teams. RESULTS: In univariate logistic regression analysis eight prehospital
      clinical symptoms proved to be statistically significant predictors of the
      development of cardiogenic shock: fainting and/or impaired consciousness, pale
      skin, cold skin, clammy skin, dyspnea, pulmonary congestion, peripheral cyanosis
      and hyperglycemia >11,1 mmol/l. In the multivariate model significant predictors
      of cardiogenic shock development were: pale skin and hyperglycemia >11.1 mmol/l.
      A risk prediction model was constructed. It proved to differentiate patients from
      study and control group highly significantly (p < 0.001). CONCLUSIONS: Patients
      with acute coronary syndrome who develop cardiogenic shock, present a different
      clinical symptoms at the moment of the first medical contact. The proposed 4S
      Scale can be used for quick assessment of risk in patients with acute coronary
      syndrome before the development of a fully-blown cardiogenic shock with severe,
      long-lasting hypotonia.

PMID- 30213589
TI  - Intra-tumoral tertiary lymphoid structures are associated with a low risk of
      early recurrence of hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Tertiary lymphoid structures (TLSs) provide a local and
      critical microenvironment for generating anti-tumor cellular and humoral immune
      responses. TLSs are associated with improved clinical outcomes in most solid
      tumors investigated to date. However, their role in hepatocellular carcinoma
      (HCC) is debated, as they have recently been shown to promote the growth of
      malignant hepatocyte progenitors in the non-tumoral liver. METHODS: We aimed to
      determine, by pathological review, the prognostic significance of both intra
      tumoral and non-tumoral TLSs in a series of 273 patients with HCC treated by
      surgical resection in Henri Mondor University Hospital. Findings were further
      validated by gene expression profiling using a public data set (LCI cohort).
      RESULTS: TLSs were identified in 47% of the tumors, by pathological review, with
      lymphoid aggregates, primary and secondary follicles in 26%, 16% and 5% of the
      cases, respectively. Univariate and multivariate analyses showed that intra
      tumoral TLSs significantly correlated with a lower risk of early relapse (<2
      years after surgery, hazard ratio 0.46, p = 0.005). Interestingly, the risk of
      recurrence was also related to the degree of TLS maturation (primary or secondary
      follicles vs. lymphoid aggregates, p = 0.01). A gene expression signature
      associated with the presence of intra-tumoral TLS was also independently
      associated with a lower risk of early relapse in the LCI cohort. No association
      between the density of TLSs located in the adjacent non-tumoral liver and early
      or late recurrence was observed. CONCLUSIONS: We have shown that intra-tumoral
      TLSs are associated with a lower risk of early relapse in 2 independent cohorts
      of patients with HCC treated by surgical resection. Thus, intra-tumoral TLSs may
      reflect the existence of ongoing, effective anti-tumor immunity. LAY SUMMARY:
      Tertiary lymphoid structures provide a critical microenvironment for generating
      anti-tumor immune responses, and are associated with improved clinical outcome in
      most cancers investigated. Their role in hepatocellular carcinoma is however
      debated. We show in the present study that intra-tumoral tertiary lymphoid
      structures are associated with a low risk of early relapse after surgical
      resection, suggesting that they reflect the existence of in situ, effective anti
      tumor immunity.

PMID- 30213591
TI  - Intestinal microcirculation and necrotizing enterocolitis: The vascular
      endothelial growth factor system.
AB  - Necrotizing enterocolitis (NEC), a leading cause of morbidity and mortality in
      preterm neonates, is a devastating disease characterized by intestinal tissue
      inflammation and necrosis. NEC pathogenesis is multifactorial but remains
      unclear. Translocation of bacteria and/or bacterial products across a weak
      intestinal barrier in the setting of impaired mucosal immunity leads to an
      exaggerated inflammatory response and secondary mucosal epithelial injury. In
      addition to prematurity, other risk factors for NEC include congenital heart
      disease, maternal pre-eclampsia with placental vascular insufficiency, severe
      anemia and blood transfusion - all conditions that predispose the intestine to
      ischemia. We recently found that maldevelopment of the intestinal
      microvasculature plays an important role in NEC pathogenesis. Here we review the
      evidence supporting a role for defective development of the intestinal mucosal
      microvasculature and perturbations of intestinal blood flow in NEC, emphasizing
      the importance of vascular endothelial growth factor (VEGF) and the VEGF receptor
      2 signaling pathway.

PMID- 30213590
TI  - Claudin-3 regulates bile canalicular paracellular barrier and cholesterol
      gallstone core formation in mice.
AB  - BACKGROUND & AIMS: Most cholesterol gallstones have a core consisting of
      inorganic and/or organic calcium salts, although the mechanisms of core formation
      are poorly understood. We examined whether the paracellular permeability of ions
      at hepatic tight junctions is involved in the core formation of cholesterol
      gallstones, with particular interest in the role of phosphate ion, a common food
      additive and preservative. METHODS: We focused on claudin-3 (Cldn3), a
      paracellular barrier-forming tight junction protein whose expression in mouse
      liver decreases with age. Since Cldn3-knockout mice exhibited gallstone diseases,
      we used them to assess the causal relationship between paracellular phosphate ion
      permeability and the core formation of cholesterol gallstones. RESULTS: In the
      liver of Cldn3-knockout mice, the paracellular phosphate ion permeability through
      hepatic tight junctions was significantly increased, resulting in calcium
      phosphate core formation. Cholesterol overdose caused cholesterol gallstone
      disease in these mice. CONCLUSION: We revealed that in the hepatobiliary system,
      Cldn3 functions as a paracellular barrier for phosphate ions, to help maintain
      biliary ion homeostasis. We provide in vivo evidence that elevated phosphate ion
      concentrations play a major role in the lifestyle- and age-related risks of
      developing cholesterol gallstone disease under cholesterol overdose. LAY SUMMARY:
      Herein, we reveal a new mechanism for cholesterol gallstone formation, in which
      increased paracellular phosphate ion permeability across hepatobiliary epithelia
      causes calcium phosphate core formation and cholesterol gallstones. Thus, altered
      phosphate ion metabolism under cholesterol overdose plays a major role in the
      lifestyle- and age-related risks of developing cholesterol gallstone disease.

PMID- 30213592
TI  - Intranasal oxytocin administration promotes emotional contagion and reduces
      aggression in a mouse model of callousness.
AB  - Deficits in empathy, the ability to share an emotion of another individual,
      constitute a hallmark of several psychopathological conditions, including conduct
      disorder. The co-occurrence of excess rates of aggression, general violation of
      societal norms and callous-unemotional traits confers specific risk for adult
      psychopathy. In the present study, we relied on a recently devised experimental
      model of conduct disorder in mice to test the potential efficacy of intranasal
      oxytocin administration. Two subgroups of BALB/cJ male mice exhibiting opposite
      profiles in emotional contagion (i.e. socially transmitted adoption of another's
      emotional states) underwent a series of tests mapping onto reactive aggression,
      information processing, perseverative behaviour, punishment-related emotional
      memory, physiological arousal and hormonal stress reactivity, with or without
      intranasal oxytocin administration (5.0 or 20.0 MUg/kg). Collectively, our data
      indicate that a trait of markedly reduced emotional contagion is associated with
      a behavioural syndrome of sensorimotor gating deficits, impaired emotional
      memory, increased aggression and stereotyped behaviours, dysregulations in the
      circadian rhythms of activity and body temperature and dampened physiological
      reactivity to external stressors. Moreover, in the absence of changes in oxytocin
      receptor density in the neural network involved in empathy-like behaviour, we
      showed that oxytocin administration normalised emotional contagion, aggression
      and behavioural stereotypies, thereby ameliorating the phenotype of mice
      characterised by deficient empathy-like behaviour. Besides, oxytocin led to a
      lower, more prolonged neuroendocrine response of the HPA-axis to stress in all
      mice. Ultimately, current data support the notion that oxytocin may constitute a
      valid therapeutic approach in disturbances characterised by abnormal aggression
      and excess callousness.

PMID- 30213593
TI  - Prognostic role of resection margin in open oncologic laryngeal surgery: survival
      analysis of a cohort of 139 patients affected by squamous cell carcinoma.
AB  - INTRODUCTION: The treatment of laryngeal squamous cell carcinoma needs accurate
      risk stratification, in order to choose the most suitable therapy. The prognostic
      significance of resection margin is still highly debated, considering the
      contradictory results obtained in several studies regarding the survival rate of
      patients with a positive resection margin. OBJECTIVE: To evaluate the prognostic
      role of resection margin in terms of survival and risk of recurrence of primary
      tumour through survival analysis. METHODS: Between 2007 and 2014, 139 patients
      affected by laryngeal squamous cell carcinoma underwent partial or total
      laryngectomy and were followed for mean of 59.44+/-28.65 months. Resection margin
      status and other variables such as sex, age, tumour grading, pT, pN, surgical
      technique adopted, and post-operative radio- and/or chemotherapy were
      investigated as prognostic factors. RESULTS: 45.32% of patients underwent total
      laryngectomy, while the remaining subjects in the cohort underwent partial
      laryngectomy. Resection margins in 73.39% of samples were free of disease, while
      in 21 patients (15.1%) anatomo-pathological evaluation found one of the margins
      to be close; in 16 subjects (11.51%) an involved resection margin was found. Only
      6 patients (4.31%) had a recurrence, which occurred in 83.33% of these patients
      within the first year of follow-up. Disease specific survival was 99.24% after 1
      year, 92.4% after 3 years, and 85.91% at 5 years. The multivariate analysis of
      all covariates showed an increased mortality rate only with regard to pN
      (HR=5.043; p=0.015) and recurrence (HR=11.586; p=0.012). Resection margin did not
      result an independent predictor (HR=0.757; p=0.653). CONCLUSIONS: Our study did
      not recognize resection margin as an independent prognostic factor; most
      previously published papers lack unanimous, methodological choices, and the
      cohorts of patients analyzed are not easy to compare. To reach a unanimous
      agreement regarding the prognostic value of resection margins, it would be
      necessary to carry out meta-analyses on studies sharing definition of resection
      margin, methodology and post-operative therapeutic choices.

PMID- 30213594
TI  - Inflammatory markers in palatine tonsils of children with obstructive sleep apnea
      syndrome.
AB  - INTRODUCTION: Obstrutive sleep apnea syndrome is characterized by repeated
      episodes of upper airway obstruction, associated with intermittent hypoxia and
      hypercapnia, and the main risk factor in childhood is adenotonsillar hypertrophy.
      The lymphocytes in these structures are responsible for local and systemic immune
      responses. OBJECTIVE: Verify the levels of the inflammatory markers, IL-1beta, IL
      4, IL-6, IL-8, IL-10, IL-15, TNF-alpha, CRP and alpha1-GP, in the tonsils of
      children with and without obstructive sleep apnea syndrome. METHODS: This cross
      sectional prospective study included 34 children with complains of snoring,
      difficulty breathing during sleep or recurrent tonsillitis. Patients underwent to
      a complete otorhinolaryngological examination, nasal endoscopy and
      polysomnography and were divided into two groups with 17 children each:
      obstructive sleep apnea syndrome group and control group. All underwent an
      adenotonsillectomy. Cytokines were measured in the collected tonsils (ELISA and
      Multiplex methods). RESULTS: Statistically significant increasing were observed
      between IL-8 and IL-10 cytokines of patients with obstructive sleep apnea when
      compared to the control group; also between c-reactive protein and alpha1-GP of
      the tonsils cortical region in children with obstructive sleep apnea syndrome
      when compared with the medullary region. There were no statistically significant
      differences for the remaining inflammatory mediators. CONCLUSION: After the
      analysis of the levels of pro and anti-inflammatory markers (IL-1beta, IL-4, IL
      6, IL-8, IL-10, Il-15, TNF-alpha, CRP, alpha1-GP) in the tonsils, we observed
      higher levels of markers IL-8 and IL-10 in pediatric patients with obstructive
      sleep apnea syndrome.

PMID- 30213595
TI  - Dicer promotes endothelial recovery and limits lesion formation after vascular
      injury through miR-126-5p.
AB  - BACKGROUND: The recovery of endothelial cells (ECs) after vascular injury is
      mainly mediated by the proliferation of resident ECs, thereby reducing neointima
      formation. The RNase Dicer processes microRNAs (miRNAs) and regulates EC function
      by controlling miRNA-mediated regulation of gene expression. This study aimed to
      investigate the impact of miRNA biogenesis in ECs on endothelial repair during
      lesion formation after vascular injury. METHODS AND RESULTS: To study the effect
      of Dicer on ECs during neointima formation, conditional deletion of Dicer was
      induced in Apoe-/- mice (EC-Dicerflox) by tamoxifen injection. Following wire
      induced injury to carotid arteries of EC-Dicerflox mice, the EC recovery was
      impaired and the neointima formation and lesional macrophage accumulation was
      increased. Moreover, conditional deletion of Dicer in ECs diminished the
      expression of miR-126-5p in EC-Dicerflox mice. Notably, reconstitution of miR-126
      5p in the injured arteries of EC-Dicerflox mice using miR-126-5p mimic, prevented
      the impaired endothelial recovery and increased lesion formation observed in EC
      Dicerflox mice. CONCLUSIONS: Deficiency of endothelial Dicer diminished
      endothelial recovery and promoted neointima formation probably due to impaired
      miR-126-5p expression. Treatment with miR-126-5p mimics promotes endothelial
      recovery and thereby limits neointima formation. Thus, miR-126-5p therapy
      represents a potential approach to improve endothelial recovery and prevent
      restenosis following vascular injury.

PMID- 30213596
TI  - Left ventricular support with Impella for high risk percutaneous coronary
      intervention. The demonstration of the hemodynamic benefit in daily practice.

PMID- 30213597
TI  - Intracoronary imaging to guide percutaneous coronary intervention: Clinical
      implications.
AB  - BACKGROUND: Over the last decade, the intra-coronary imaging (ICI) has emerged to
      guide percutaneous coronary intervention (PCI), thus overcoming the limitations
      of "luminology" offered by angiography. METHODS: In this review, we aim at purely
      focusing on the clinical implications of the employment of ICI in the routine
      practice, thus providing suggestions for future applications. In particular, we
      will describe the principal contributions and implications of ICI in the
      following different clinical settings: 1) assessment of clinical and imaging
      outcomes of PCI; 2) guiding PCI before and after stent implantation; 3)
      identification of mechanisms of stent failure. RESULTS: Several studies showed
      the capability of ICI in assessing the clinical and imaging outcomes of PCI. In
      particular, they have compared the ICI-guided PCI with the angiography-guided
      procedures, emphasizing the advantages of using imaging. Indeed, ICI can
      characterize the coronary plaque, provide a precise estimation of the coronary
      stenosis, select the appropriate method of intervention, and optimize stent
      deployment and lesion coverage. Finally, ICI has been shown to be useful to point
      out the mechanisms of stent failure. CONCLUSIONS: ICI can facilitate decision
      making in patients with unclear angiographic findings, guide-selected
      interventions and optimize the final PCI results in complex lesions or. in high
      risk patients. Finally, by the identification of specific mechanisms of stent
      failure, the ICI can allow to adopt a tailored therapy for the singles cases.

PMID- 30213598
TI  - Long term management of patients after myocardial infarction: How and by whom?

PMID- 30213599
TI  - Intermodality variation of aortic dimensions: How, where and when to measure the
      ascending aorta.
AB  - BACKGROUND: No established reference-standard technique is available for
      ascending aortic diameter measurements. The aim of this study was to determine
      agreement between modalities and techniques. METHODS: In patients with aortic
      pathology transthoracic echocardiography, computed tomography angiography (CTA)
      and magnetic resonance angiography (MRA) were performed. Aortic diameters were
      measured at the sinus of Valsalva (SoV), sinotubular junction (STJ) and tubular
      ascending aorta (TAA) during mid-systole and end-diastole. In echocardiography
      both the inner edge-to-inner edge (I-I edge) and leading edge-to-leading edge (L
      L edge) methods were applied, and the length of the aortic annulus to the most
      cranial visible part of the ascending aorta was measured. In CTA and MRA the I-I
      method was used. RESULTS: Fifty patients with bicuspid aortic valve (36 +/- 13
      years, 26% female) and 50 Turner patients (35 +/- 13 years) were included.
      Comparison of all aortic measurements showed a mean difference of 5.4 +/- 2.7 mm
      for the SoV, 5.1 +/- 2.0 mm for the STJ and 4.8 +/- 2.1 mm for the TAA. The
      maximum difference was 18 mm. The best agreement was found between
      echocardiography L-L edge and CTA during mid-systole. CTA and MRA showed good
      agreement. A mean difference of 1.5 +/- 1.3 mm and 1.8 +/- 1.5 mm was
      demonstrated at the level of the STJ and TAA comparing mid-systolic with end
      diastolic diameters. The visible length of the aorta increased on average 5.3 +/-
      5.1 mmW during mid-systole. CONCLUSIONS: MRA and CTA showed best agreement with L
      L edge method by echocardiography. In individual patients large differences in
      ascending aortic diameter were demonstrated, warranting measurement
      standardization. The use of CTA or MRA is advised at least once.

PMID- 30213600
TI  - Association between dabigatran etexilate and risk of myocardial infarction.

PMID- 30213601
TI  - Reply to the letter "Not only the global longitudinal strain, but we can do more
      for the non-ST elevation acute coronary syndrome patients by speckle-tracking
      echocardiography".

PMID- 30213602
TI  - Comment on "Non-vitamin K antagonists oral anticoagulants are as safe and
      effective as warfarin for cardioversion of atrial fibrillation: A systematic
      review and meta-analysis".

PMID- 30213603
TI  - Circular RNA DLGAP4 ameliorates cardiomyocyte apoptosis through regulating BCL2
      via targeting miR-143 in myocardial ischemia-reperfusion injury.

PMID- 30213604
TI  - Nardilysin: A potential biomarker for the early diagnosis of acute coronary
      syndrome.

PMID- 30213605
TI  - Timing of invasive septal reduction therapies and outcome of patients with
      obstructive hypertrophic cardiomyopathy.
AB  - BACKGROUND: Whether early vs. delayed referral to septal reduction therapies
      (SRT, alcohol septal ablation or surgical myectomy) bears prognostic relevance in
      hypertrophic obstructive cardiomyopathy (HOCM) is unresolved. We analyzed the
      impact of SRT timing on the outcome of HOCM patients. METHODS: We followed 126
      patients for 5 +/- 4 years after SRT (mean age 53 +/- 15 years; 55 post-ASA and
      71 post-SM). Based on time-to-treatment (TTT; from HOCM diagnosis to SRT),
      patients were divided into three groups: "<3" years, N = 50; "3-5" years, N = 25;
      ">5" years, N = 51. RESULTS: Patients with TTT > 5 years were younger at
      diagnosis and more often had atrial fibrillation (AF). Left ventricular outflow
      tract (LVOT) gradients were comparable in the 3 TTT groups. Two patients died
      peri-operatively, all with TTT > 5. Long-term, 8 patients died (3 suddenly and 5
      due to heart failure). Mortality increased progressively with TTT (2% vs. 4% vs.
      12% for TTT "<3", "3-5", and ">5" years, p for trend = 0.039). Independent
      predictors of disease progression (new-onset AF, worsening to NYHA III/IV
      symptoms, re-intervention or death) were TTT ("3-5" vs. "<3" years: HR: 4.988,
      95%CI: 1.394-17.843; ">5" vs. "<3" years: HR: 3.420, 95%CI: 1.258-9.293, overall
      p-value = 0.025), AF at baseline (HR: 1.896, 95%CI: 1.002-3.589, p = 0.036) and
      LVOT gradient (HR per mm Hg increase: 1.022, 95%CI: 1.007-1.024, p = 0.023).
      CONCLUSIONS: Delay in SRT referral has significant impact on long-term outcome of
      patients with HOCM, particularly when >5 years from first detection of gradient,
      even when successful relief of symptoms and gradient is achieved. Earlier
      interventions are associated with lower complication rates and better prognosis,
      suggesting the importance of timely SRT to maximize treatment benefit and prevent
      late HOCM-related complications.

PMID- 30213606
TI  - An ophthalmologic complication of Whipple's disease: Case report.

PMID- 30213607
TI  - [Spontaneous choroidal hemorrhage associated with novel oral anticoagulants: A
      report of two cases and literature review].
AB  - New direct oral anticoagulants (DOAC) have been approved for treatment and
      prevention of some thromboembolic diseases: acute and chronic phase of
      thromboembolic disease, deep venous thrombosis prophylaxis in orthopedic surgery
      and prevention of stroke in patients with atrial fibrillation. These molecules
      are an alternative to heparins and vitamin K antagonists. Among these,
      rivaroxaban (Xarelto(r), Bayer Schering Pharma) is a direct factor Xa inhibitor,
      and dabigatran etexilate (Pradaxa(r), Boehringer Ingelheim) is a direct free
      thrombin inhibitor. These molecules are almost the ideal anticoagulant: oral
      administration, few drug and food interactions, wide therapeutic target, and
      especially no lab monitoring. However, their use remains associated with
      hemorrhagic complications such as gastrointestinal, intracranial or urinary
      hemorrhages. We describe two clinical cases of spontaneous choroidal hemorrhage
      in patients treated with direct oral anticoagulants (rivaroxaban and dabigatran
      etexilate) for atrial fibrillation. These cases show that an ocular hemorrhagic
      risk exists with these drugs. Patients treated with DOAC should have the
      therapeutic dose adjusted based on creatinine clearance. Special monitoring
      should be performed in patients with age-related macular degeneration or with
      hypertension even though meta-analysis shows that the risk of intraocular
      bleeding is reduced by 22% compared with warfarin.

PMID- 30213608
TI  - Revascularization after branch retinal vein occlusion studied by OCT angiography:
      Report of three cases.

PMID- 30213609
TI  - Comparison of the effect of ranibizumab and dexamethasone implant on serous
      retinal detachment in diabetic macular edema.
AB  - PURPOSE: To compare the efficacy of intravitreal ranibizumab (IVR) and
      intravitreal dexamethasone implant (IDI) on neurosensory retinal detachment (SRD)
      associated with diabetic macular edema (DME) in the early treatment period.
      METHODS: This was a retrospective, interventional, case-control study. After
      three monthly loading doses of IVR or an initial IDI injection, the changes in
      best-corrected visual acuity (BCVA), central macular thickness (CMT) on OCT, and
      presence and height of SRD were evaluated. RESULTS: The IVR and IDI groups
      consisted of 101 and 35 eyes, respectively. The mean changes in CMT in the IVR
      and IDI groups were 204.4+/-176.6 and 311.4+/-163, respectively (P<0.001). The
      mean changes in SRD height in the IVR and IDI groups were 133.6+/-92.1 and
      168.6+/-103.9MUm, respectively. The decrease in SRD height was significantly
      greater in the IDI group than in the IVR group (P=0.002). The SRD resolved
      completely in 72.2% and 71.4% of the patients in the IVR and IDI groups,
      respectively (P=0.9). CONCLUSION: The mean reduction in CMT and SRD height was
      greater in the IDI group than in the IVR group. There was a negative correlation
      between baseline best-corrected visual acuity (BCVA) and SRD height and also
      between BCVA and CMT.

PMID- 30213610
TI  - Vitamin D deficiency and graft-versus-host disease in hematopoietic stem cell
      transplant population.
AB  - Vitamins are the organic compounds that have long been known to play a
      significant role in our body by functioning as hormones and antioxidants. Vitamin
      D, a fat-soluble vitamin, is the main regulator of calcium hemostasis in our
      body. At the same time, it is also known to show its potential effects on the
      immune system by modulating the differentiation, activation, and proliferation of
      T and B lymphocytes. The immunomodulatory properties of vitamin D are also known
      to have a crucial role in the prevention and treatment of graft-versus-host
      disease. Patients undergoing hematopoietic stem cell transplantation are
      particularly at risk of vitamin D deficiency. This review article expands our
      understanding of vitamin D, its immunomodulatory effects, and its role in
      prevention and treatment of graft-versus-host disease.

PMID- 30213612
TI  - Penicillin allergy skin testing is safe in pre-lung transplant patients with low
      lung volumes.

PMID- 30213611
TI  - Comparing Asthma Control Questionnaire (ACQ) and National Asthma Education and
      Prevention Program (NAEPP) asthma control criteria.
AB  - BACKGROUND: Adequate assessment of control is critical to asthma management. The
      Asthma Control Questionnaire (ACQ) and the National Asthma Education and
      Prevention Program (NAEPP) criteria are commonly used measures of asthma control.
      OBJECTIVES: To examine the associations between the ACQ and NAEPP criteria and
      compare the validity in association with lung function, asthma exacerbation, and
      quality of life. METHODS: The ACQ and the NAEPP criteria were administered to 373
      adolescents with asthma aged 12 to 20 years. The 2 measures correlated with
      forced expiratory volume in 1 second (FEV1), asthma exacerbation (oral
      corticosteroid use, hospitalization, and emergency department [ED] use) in the
      past 12 months, and quality of life. RESULTS: Agreement between the ACQ and NAEPP
      criteria was moderate (kappa = 0.40-0.61). Neither of the 2 measures was a
      reliable predictor of FEV1 less than 80% because of the high rate of false
      positive results for the ACQ (68%) and low sensitivity for the NAEPP (49%). The
      NAEPP identified more cases of uncontrolled asthma (84.6%) than the ACQ (64.6%).
      The ACQ was a significant predictor of recent oral corticosteroid use,
      hospitalization, and ED visits (area under the curve = 0.66, 0.66, and 0.64,
      respectively; P < .001), as was NAEPP (area under the curve = 0.63, 0.66, and
      0.61, respectively; P < .001). Both measures were significantly associated with
      quality of life, and the associations were particularly strong for the ACQ (r = 
      0.87 for symptom subscale, r = -0.76 for activity subscale, and r = -0.78 for
      emotional function subscale). CONCLUSION: Neither the ACQ nor the NAEPP appears
      to reliably predict lung function, whereas both measures reasonably associate
      with acute asthma exacerbation. The ACQ may be the superior measure in gauging
      the psychosocial effect of asthma control given its particularly strong
      associations with quality of life. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT02293499.

PMID- 30213613
TI  - Development of HLA-matched vascular grafts utilizing decellularized human
      umbilical artery.
AB  - Worldwide, there is a great need of small diameter vascular grafts that can be
      used in human disorders such as cardiovascular and peripheral vascular disease.
      Until now, severe adverse reactions are caused from the use of synthetic or
      animal derived grafts, while the use of autologous vessels is restricted only in
      a small number of patients. The limited availability of the vessels might be
      resolved by the use of HLA-matched vascular grafts utilizing the decellularized
      human umbilical arteries. In this study, human umbilical arteries were
      decellularized and then repopulated with Mesenchymal Stem Cells. The HLA-genotype
      of the repopulated grafts, analyzed by Next Generation Sequencing technology,
      indicated their successful production. The HLA-matched vascular grafts could be
      generated efficiently and might be used in personalized medicine.

PMID- 30213614
TI  - Alcohol consumption increase susceptibility to pneumococcal pneumonia in a
      humanized murine HIV model mediated by intestinal dysbiosis.
AB  - Alcohol use in persons living with HIV (PLWH) worsens the severity of bacterial
      pneumonia. However, the exact mechanism(s) by which this occurs remain ill
      defined. We hypothesized that alcohol in the setting of HIV infection decreases
      S. pneumoniae clearance from the lung through mechanisms mediated by the gut
      microbiota. Humanized BLT (bone marrow, liver, thymus) mice were infected with
      1x104 TCID50 of HIV (BAL and JRCSF strains) via IP injection. One week post HIV
      infection animals were switched to a Lieber-DeCarli 5% ethanol diet or an
      isocaloric control diet for 10 days, alcohol-fed animals were also given 2 binges
      of 2 g kg-1 ethanol on days 5 and 10. Feces were also collected, banked, and the
      community structures were analyzed. Mice were then infected with 1x105 CFU of S.
      pneumoniae and sacrificed 48 hours later. HIV-infected mice had viral loads of
      ~2x104 copies/mL of blood one week post infection, and exhibited an ~57% decrease
      in the number of circulating CD4+ T-cells at the time of sacrifice. Fecal
      microbial community structure was significantly different in each of the feeding
      groups, as well as with HIV infection. Alcohol-fed mice had a significantly
      higher burden of S. pneumoniae 48 hours post infection, regardless of HIV status.
      In follow-up experiments, female C57BL/6 mice were treated with a cocktail of
      antibiotics daily for two weeks and recolonized by gavage with intestinal
      microbiota from HIV+ ethanol-fed, HIV+ pair-fed, HIV- ethanol-fed, or HIV- pair
      fed mice. Recolonized mice were then infected with S. pneumoniae and sacrificed
      48 hours later. The intestinal microbiota from alcohol-fed mice (regardless of
      HIV status) significantly impaired clearance of S. pneumoniae. Collectively,
      these data indicate that alcohol-feeding, as well as alcohol-associated
      intestinal dysbiosis compromise pulmonary host defense against pneumococcal
      pneumonia. Whether HIV infection acts synergistically with alcohol-use in
      impairing pulmonary host defense will require additional study.

PMID- 30213615
TI  - A checklist of the Anopheles mosquito species (Diptera: Culicidae) in Bhutan.
AB  - The present paper records, for the first time, the Anopheles fauna of Bhutan,
      determined from surveys conducted from 2007 to early 2018. Adult mosquitoes were
      collected mainly on cattle bait and occasionally in human landing catches.
      Collections of immature stages were performed in various aquatic habitats. Larvae
      were preserved or reared to adults. Identification was based on morphological
      characters using available keys. A total of 30 species were identified, including
      nine species of subgenus Anopheles and 21 species of subgenus Cellia.
      Distribution and collection data are provided with notes on the locations and
      habitats of the species. Anopheles pseudowillmori is suspected to be a vector of
      malarial parasites in the plains and hilly forested areas of the country because
      it is widely distributed and the most common species collected in human landing
      catches. Notes also include observed morphological variation observed in An.
      baileyi and An. lindesayi, which differ from the type forms. Corrections are made
      for previous reports of Anopheles in Bhutan. The need for further surveys and
      molecular identification of members of species complexes and morphological
      variants is emphasized.

PMID- 30213616
TI  - Three new records of the genus Lutzomyia of the subgenus Helcocyrtomyia (Diptera:
      Psychodidae: Phlebotominae) from Southwestern Brazilian Amazonia.
AB  - The sand fly phlebotomine fauna of the Brazilian municipality of Assis Brasil,
      Acre was sampled between April 2013 and March 2014 using modified CDC light
      traps. A total of 22,334 sand flies were collected, 41 of them belonging to three
      species: Lutzomyia gonzaloi, Lu. kirigetiensis and Lu. munaypata, of the subgenus
      Helcocyrtomyia, which have previously only been recorded in Peru. This paper
      presents their first reported collection in Brazil.

PMID- 30213617
TI  - Dietary Intervention to Increase Fruit and Vegetable Consumption in Breastfeeding
      Women: A Pilot Randomized Trial Measuring Inflammatory Markers in Breast Milk.
AB  - BACKGROUND: Diets rich in fruits and vegetables (F/V) can reduce the inflammatory
      profile of circulating cytokines and potentially decrease the risk of breast
      cancer. However, the extent to which a diet rich in F/V alters cytokine levels in
      breast tissue remains largely unknown. Breast milk provides a means of assessing
      concentrations of secreted cytokines in the breast microenvironment and is a
      potential tool for studying the effects of diet on inflammation in breast tissue
      and breast cancer risk. OBJECTIVE: The aim of this pilot randomized trial was to
      test the feasibility of increasing F/V intake in breastfeeding women and of
      measuring changes in markers of inflammation in breast milk. DESIGN AND
      INTERVENTION: Participants randomized to the intervention (n=5) were provided
      weekly boxes of F/V, along with dietary counseling, to increase consumption of
      F/V to 8 to 10 daily servings for 12 consecutive weeks. Controls (n=5) were
      directed to the US Department of Agriculture's "ChooseMyPlate" diet for pregnancy
      and breastfeeding. PARTICIPANTS/SETTING: Ten breastfeeding women consuming fewer
      than five servings of F/V per day, as estimated by the National Institutes of
      Health "All-Day" Fruit and Vegetable Screener (F/V Screener), were recruited
      through flyers and a lactation consultant between February and May 2016 in the
      Western Massachusetts area. MAIN OUTCOME MEASURES: Baseline demographic and F/V
      intake data were collected during enrollment. At week 1 and week 13 (final) home
      visits, participants provided milk samples and anthropometric measurements were
      recorded. Participants completed F/V screeners at baseline and at study end.
      Adiponectin, leptin, C-reactive protein, and 11 additional cytokines were
      measured in breast milk collected at weeks 1 and 13. STATISTICAL ANALYSES: F/V
      consumption at baseline and after the final visit, and between controls and
      intervention groups, was compared with dependent and independent t tests,
      respectively. Differences between cytokine levels at weeks 1 and 13 were assessed
      with a mixed-effects repeated-measures model. RESULTS: All women in the
      intervention increased F/V intake and were consuming more servings than controls
      by week 13; daily serving of F/V at baseline and final visit: controls=1.6 and
      2.0, diet=2.6 and 9.9. Most cytokines were detected in the majority of milk
      samples: 12 were detected in 90% to 100% of samples, one was detected in 75% of
      samples, and one was detected in 7.5% of samples; coefficients of variation were
      below 14% for 11 of the cytokines. CONCLUSIONS: These preliminary findings
      indicate that it is feasible to significantly increase F/V intake in
      breastfeeding women and provide support for conducting a larger diet intervention
      study in breastfeeding women, in which longer-term benefits of the intervention
      are assessed.

PMID- 30213618
TI  - The Impact of 1 Year of Healthier School Food Policies on Students' Diets During
      and Outside of the School Day.
AB  - BACKGROUND: In 2012, Massachusetts implemented both the updated national school
      meal standards and comprehensive competitive food/beverage standards that closely
      align with current national requirements for school snacks. OBJECTIVES: This
      study examines the impact of these combined standards on school meal and snack
      food selections, as well as food choices outside of school. In addition, this
      study examines the impact of these standards on nutrients consumed. DESIGN: The
      NOURISH (Nutrition Opportunities to Understand Reforms Involving Student Health)
      Study was an observational cohort study conducted among students from spring 2012
      to spring 2013. PARTICIPANTS/SETTING: One hundred sixty students in 12 middle
      schools and high schools in Massachusetts completed two 24-hour recalls before
      (spring 2012) and after implementation (spring 2013) of the updated standards.
      MAIN OUTCOME MEASURES: Changes in school meals, competitive food, and after
      school snack selection, as well as nutrients consumed outside of school were
      examined. STATISTICAL ANALYSES PERFORMED: Logistic regression and mixed-model
      analysis of variance were used to examine food selection and consumption.
      RESULTS: After implementation, 13.6% more students chose a school meal (70.1% vs
      56.5%; P=0.02). There were no differences in competitive food purchases but a
      significant decrease in the number of after-school unhealthy snacks consumed
      (0.69 [standard error=0.08] vs 1.02 [standard error=0.10]; P=0.009). During the
      entire day, students consumed, on average, 22 fewer grams of sugar daily after
      implementation compared with before implementation (86 g vs 108 g; P=0.002).
      CONCLUSIONS: With the reduction in the number of unhealthy school snacks,
      significantly more students selected school meals. Students did not compensate
      for lack of unhealthy snacks in school by increased consumption of unhealthy
      snacks outside of school. This provides important new evidence that both national
      school meal and snack policies may improve daily diet quality and should remain
      strong.

PMID- 30213619
TI  - The Use of the Plate-by-Plate Approach for Adolescents Undergoing Family-Based
      Treatment.

PMID- 30213620
TI  - Memantine attenuated alcohol withdrawal-induced anxiety-like behaviors through
      down-regulating NR1-CaMKII-ERK signaling pathway.
AB  - Alcohol abuse and anxiety disorders often occur concurrently, but their
      underlying cellular mechanisms remain unclear. N-methyl-D-aspartic acid receptors
      (NMDARs) have recently received attention from those interested in the
      neurobiology of anxiety. A chronic alcohol exposure rat model (28 consecutive
      days of 20% alcohol intake and 6 h of withdrawal) was established. Here, we
      investigated the NMDAR1 (NR1), Ca2+/calmodulin-dependent protein kinase II
      (CaMKII) and extracellular signal-regulated kinases (ERK) pathway in the
      modulation of anxiety-like behaviors in rats exposed to an open field and
      elevated plus maze (EPM) through systematic injections of memantine (a NMDAR
      inhibitor). We found that the NR1-CaMKII-ERK signaling pathway was activated
      after alcohol withdrawal in medial prefrontal cortex (mPFC) and nucleus accumbens
      shell (NAcSh) but not core (NAcC). Memantine treatment greatly ameliorated
      anxiety-like behavior in the rats experiencing alcohol withdrawal. Moreover,
      memantine uniformly suppressed the phosphorylation of NR1-CaMKII-ERK pathway
      induced by alcohol withdrawal. Our results suggest that activation of the NR1
      CaMKII-ERK pathway in the mPFC and NAcSh is an important contributor to the
      molecular mechanisms underlying alcohol withdrawal-induced anxiety behaviors.
      NMDAR signaling pathway inhibitors are thus potential therapeutics for treating
      alcohol abuse.

PMID- 30213621
TI  - Peucedani Japonici Radix ameliorates lipopolysaccharide-induced neuroinflammation
      by regulating microglial responses.
AB  - Neuroinflammation is an inflammatory process within the central nervous system
      that is mediated by microglial activation, which releases pro-inflammatory
      mediators leading to neurodegeneration. In this study, we investigated the
      effects of Peucedani Japonici Radix (PJR), a medicinal herb traditionally used in
      East Asia to treat neuroinflammation both in vitro and in vivo. First, we
      examined the effects of PJR on pro-inflammatory mediators in lipopolysaccharide
      (LPS)-stimulated BV-2 microglial cells. The results showed that PJR suppressed
      the LPS-induced increase of several inflammatory factors, such as nitric oxide,
      inducible nitric oxide synthase, cyclooxygenase-2, prostaglandin E2, interleukin
      1beta, and tumor necrosis factor-alpha. We also revealed that PJR inhibited the
      nuclear factor kappa B (NF-kappaB) pathway, which is the upstream modulator of
      inflammatory processes. Furthermore, to confirm the regulatory effects of PJR on
      microglia in vivo, we measured the number of ionized calcium-binding adapter
      molecule 1-positive cells in mouse brains and found that PJR treatment reduced
      microglial activation. Taken together, these results suggest that PJR inhibits
      microglia-mediated neuroinflammation through the modulation of NF-kappaB
      signaling and has the therapeutic potential to prevent inflammation-related
      neurodegenerative diseases.

PMID- 30213622
TI  - Effects of agomelatine on electrocorticogram activity on penicillin-induced
      seizure model of rats.
AB  - Agomelatine is a new antidepressant drug acting as an antagonist of 5
      hydroxytryptamine receptor 2C (5-HTR2C) and agonist of melatonergic receptors 1
      and 2 (MT1 and MT2). Because of this dual action, it is an atypical
      antidepressant. The aim of this study was to investigate chronic anticonvulsant
      effects of agomelatine on penicillin-induced epilepsy model. Adult male Sprague
      Dawley rats divided into four groups and were administered with tap water
      (vehicle), and agomelatine doses of 10 mg/kg, 50 mg/kg and 100 mg/kg for 14 days
      via oral gavage. After the last doses were given, epileptic seizures were induced
      by intracortical penicillin (500 IU/2.5 MUl) application in rats under urethane
      (1.25 g/kg intraperitoneal) anesthesia. Electrocorticogram (ECoG) recordings were
      obtained from the somatomotor cortex through 90 min, and spike frequencies and
      amplitudes were analyzed. The spike frequency analyses revealed that only 50
      mg/kg agomelatine administration decreased the spike frequencies of
      hypersynchronous discharge of neurons caused by penicillin (p < 0.05). No
      significant differences in amplitudes between experimental groups were observed.
      In addition, mRNA expressions of vesicular glutamate transporter 1 (VGLUT1) and
      vesicular gamma-aminobutyric acid transporter (VGAT) in response to the
      agomelatine active dose, 50 mg/kg, showed no significant effect of agomelatine on
      the mRNA expression. Our results indicate that chronic treatment with agomelatine
      may have potential anticonvulsant effects. Agomelatine may be a promising drug
      for epilepsy patients having depression due to its antiepileptic and
      antidepressant effects.

PMID- 30213623
TI  - [A rare infectious etiology of COPD exacerbation].
AB  - Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder.
      Its exacerbation is infectious in more than half of the cases: with viral
      priority, while parasitic causes remain exceptional. In this work, we report a
      case of a COPD exacerbation caused by a visceral leishmaniasis (VL) complicated
      by a macrophage activation syndrome in an adult living in a Moroccan non-endemic
      region for this of leismaniasis form. In such atypical clinical feature, the
      diagnosis of VL was based on the myelogram after presence of peripheral
      cytopenia. Despite the seriousness of these pathologies, the early and specific
      treatment of VL allows a quickly improvement in the disorders caused by these
      diseases.

PMID- 30213624
TI  - [Toxicity of immune checkpoints inhibitors].
AB  - INTRODUCTION: Anti-tumoral immunotherapy is currently the basis of a profound
      modification of therapeutic concepts in oncology, in particular since the arrival
      of immune checkpoint inhibitors (ICI). In addition to their efficacy profile,
      these immune-targeted agents also generate adverse events. With the increasing
      use of ICI for a growing number of tumor types, awareness of immunotherapy
      related adverse events is essential to ensure prompt diagnosis and effective
      management of these potentially serious adverse events. BACKGROUND: Cytotoxic T
      lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co
      inhibitory receptors that are expressed on activated T cells against which
      therapeutic blocking antibodies have reached routine clinical use. Immune
      checkpoint blockade can induce inflammatory adverse effects, termed immune
      related adverse events (irAEs), which resemble autoimmune disease. Though severe
      irAEs remain rare, they can be fatal if not diagnosed and treated in an
      appropriate manner. OUTLOOK AND CONCLUSION: Additional studies are needed to
      better understand the clinical characteristics and chronology of these adverse
      effects and to clarify their pathophysiological mechanisms.

PMID- 30213625
TI  - Advances in asthma in 2017: Mechanisms, biologics, and genetics.
AB  - This review summarizes some of the most significant advances in asthma research
      over the past year. We first focus on novel discoveries in the mechanism of
      asthma development and exacerbation. This is followed by a discussion of
      potential new biomarkers, including the use of radiographic markers of disease.
      Several new biologics have become available to the clinician in the past year,
      and we summarize these advances and how they can influence the clinical delivery
      of asthma care. After this, important findings in the genetics of asthma and
      heterogeneity in phenotypes of the disease are explored, as is the role the
      environment plays in shaping the development and exacerbation of asthma. Finally,
      we conclude with a discussion of advances in health literacy and how they will
      affect asthma care.

PMID- 30213626
TI  - Artemisia species pollen (mugwort) as a major vector for ambient LPS: Brothers in
      harm?

PMID- 30213627
TI  - Rhinitis in children and adolescents with asthma: Ubiquitous, difficult to
      control, and associated with asthma outcomes.
AB  - BACKGROUND: Rhinitis and asthma are linked, but substantial knowledge gaps in
      this relationship exist. OBJECTIVE: We sought to determine the prevalence of
      rhinitis and its phenotypes in children and adolescents with asthma, assess
      symptom severity and medication requirements for rhinitis control, and
      investigate associations between rhinitis and asthma. METHODS: Seven hundred
      forty-nine children with asthma participating in the Asthma Phenotypes in the
      Inner-City study received baseline evaluations and were managed for 1 year with
      algorithm-based treatments for rhinitis and asthma. Rhinitis was diagnosed by
      using a questionnaire focusing on individual symptoms, and predefined phenotypes
      were determined by combining symptom patterns with skin tests and measurement of
      serum specific IgE levels. RESULTS: Analyses were done on 619 children with
      asthma who completed at least 4 of 6 visits. Rhinitis was present in 93.5%, and
      phenotypes identified at baseline were confirmed during the
      observation/management year. Perennial allergic rhinitis with seasonal
      exacerbations was most common (34.2%) and severe. Nonallergic rhinitis was least
      common (11.3%) and least severe. The majority of children remained symptomatic
      despite use of nasal corticosteroids with or without oral antihistamines.
      Rhinitis was worse in patients with difficult-to-control versus easy-to-control
      asthma, and its seasonal patterns partially corresponded to those of difficult-to
      control asthma. CONCLUSION: Rhinitis is almost ubiquitous in urban children with
      asthma, and its activity tracks that of lower airway disease. Perennial allergic
      rhinitis with seasonal exacerbations is the most severe phenotype and most likely
      to be associated with difficult-to-control asthma. This study offers strong
      support to the concept that rhinitis and asthma represent the manifestations of 1
      disease in 2 parts of the airways.

PMID- 30213628
TI  - Identification of linear B-cell epitopes on the phosphoprotein of canine
      distemper virus using four monoclonal antibodies.
AB  - The highly contagious canine distemper virus (CDV) is a non-segmented single
      stranded negative-sense RNA virus, which belongs to the Morbillivirus genus of
      the Paramyxoviridae family. The phosphoprotein (P) of CDV plays the important
      role in the virus replication and pathogenesis. In this study, we characterized
      four monoclonal antibodies (MAbs), designated as Pc7, Pc8, Pc11 and Pc25 MAbs
      against the P protein of CDV-PS strain. A series of overlapping P protein-derived
      peptides representing the CDV-PS phosphoprotein (aa232-507) were screened to
      identify linear peptide epitopes recognized by each MAb. Finally, four epitopes,
      238SHGMGIVAGSTN249 (E2-9), 264GPSVSAENVRQ274 (E6-2), 390INPELRPIIGR400 (E27-2)
      and 252TQSALKSTG260 (E4-9), are minimal linear epitopes recognized by the Pc7,
      Pc8, Pc11 and Pc25 MAbs, respectively. Each identified B-cell epitope was able to
      be recognized by CDV positive dog serum. Alignment analysis of the amino acid
      sequences indicated that the linear B-cell epitope of the Pc11 MAb is relatively
      conserved among different CDV strains, but the linear B-cell epitopes recognized
      by Pc7, Pc8 and Pc25 MAbs are not conserved among CDV strains. Our results
      revealed that the E27-2 peptide might be a common B-cell binding epitope of CDV
      antibodies. These findings may provide a useful basis for the development of new
      diagnostic assays for CDV.

PMID- 30213629
TI  - Graphene-based materials: The missing piece in nanomedicine?
AB  - Nanomedicine utilizes biocompatible nanomaterials for therapeutic as well as
      imaging purposes for the treatment of various diseases including cancer,
      neurological disorders and wound infections. Graphene and its modified
      nanostructures have attracted much attention in recent years in nanomedicine
      owing to their scalable and cost effective preparation and physiochemical
      features (high specific surface area, ease in conjugation to
      peptides/antibodies/proteins and biocompatibility). However, the limited
      fabrication, functionalization, and in vivo functionalities available in
      literature indicate inconsistencies regarding the factors affecting in vivo
      metabolisms, biodistribution as well as toxicity patterns of graphene. It appears
      that redox signaling pathways, and their proper use to target specific diseases
      and to improve biocompatibility and interplay between size and optical properties
      are key determinants to investigate the metabolic fate of such materials. This
      featured letter provides key insights into the significance and multifunctional
      roles of redox regulated species in graphene-based materials which can be used to
      closely mimic therapeutic functions, navigating new paths to nanomedicine and
      synthetic biology. Furthermore, this letter focuses on the missing
      functionalities and challenges in using graphene-based materials as both nano
      carriers and nano-drugs in various biomedical sectors which might be favorable
      for multiple payloads and drug targeting in upcoming years.

PMID- 30213630
TI  - Norepinephrine induces rapid and long-lasting phosphorylation and redistribution
      of connexin 43 in cortical astrocytes.
AB  - Norepinephrine (NE) modulates brain functions depending on both the internal and
      external environment. While the neuromodulatory actions of NE have been well
      characterized, the response and involvement of cortical astrocytes to
      physiological noradrenergic systems remain largely unknown, especially at the
      molecular level. In this study, we biochemically characterize the action of NE on
      astrocytes of the murine neocortex. NE stimulation of acute brain slices rapidly
      increase phosphorylation of connexin 43 (Cx43) at Serine (Ser) 368, in slices
      from both juvenile and adolescent animals. The phosphorylation is mediated by the
      protein kinase C (PKC) pathway under the alpha1-adrenergic receptor and remains
      elevated for tens of minutes following brief exposure to NE, well after the
      intracellular calcium level returns to normal level, suggesting the plastic
      nature of this phosphorylation event. Importantly, this phosphorylation event
      persists in the absence of neuronal transmissions, suggesting that the effect of
      NE on Cx43 phosphorylation is induced directly on astrocytes. Furthermore, these
      NE-induced phosphorylations are associated with biochemical dissociation of Cx43
      from gap-junctional plaques to non-junctional compartments. Finally, we show that
      pharmacological manipulation of the noradrenergic system using psychoactive drugs
      modulates phosphorylation of Cx43 in the cerebral cortex in vivo. These data
      suggest that NE acts directly on astrocytes in parallel with neurons and
      modulates functionally critical connexin channel proteins in a plastic manner.
      Thus, plasticity of astrocytes induced by the "gliomodulatory" actions of NE may
      play important roles in their physiological as well as pharmacological actions in
      the brain.

PMID- 30213631
TI  - Circular orientation fluorescence emitter imaging (COFEI) of rotational motion of
      motor proteins.
AB  - Single-molecule fluorescence polarization technique has been utilized to detect
      structural changes in biomolecules and intermolecular interactions. Here we
      developed a single-molecule fluorescence polarization measurement system, named
      circular orientation fluorescence emitter imaging (COFEI), in which a ring
      pattern of an acquired fluorescent image (COFEI image) represents an orientation
      of a polarization and a polarization factor. Rotation and pattern change of the
      COFEI image allow us to find changes in the polarization by eye and further
      values of the parameters of a polarization are determined by simple image
      analysis with high accuracy. We validated its potential applications of COFEI by
      three assays: 1) Detection of stepwise rotation of F1-ATPase via single quantum
      nanorod attached to the rotary shaft gamma; 2) Visualization of binding of
      fluorescent ATP analog to the catalytic subunit in F1-ATPase; and 3) Association
      and dissociation of one head of dimeric kinesin-1 on the microtubule during its
      processive movement through single bifunctional fluorescent probes attached to
      the head. These results indicate that the COFEI provides us the advantages of the
      user-friendly measurement system and persuasive data presentations.

PMID- 30213632
TI  - Distinct modulation of group I ribozyme activity among stereoisomers of a
      synthetic pentamine with structural constraints.
AB  - Among cationic molecules that can modulate ribozyme activities, polyamines act as
      both activator and inhibitor of ribozyme reactions partly due to their structural
      flexibility. Restriction of structural flexibility of polyamines may allow them
      to emphasize particular modulation effects. We examined eight stereoisomers of a
      synthetic pentamine bearing three cyclopentane rings. In the reaction of a
      structurally unstable group I ribozyme, three stereoisomers exhibited distinct
      effects as inhibitor, an additive with a neutral effect, and also as an
      activator.

PMID- 30213633
TI  - Crystal structure of SSB complexed with inhibitor myricetin.
AB  - Single-stranded DNA-binding protein (SSB) is essential for all DNA-dependent
      cellular processes. SSB inhibitors have been recently suggested as broad-spectrum
      antibacterial agents in antibiotic development. In this paper, we report the
      first inhibitor-complexed crystal structure of SSB from Pseudomonas aeruginosa
      PAO1 (PaSSB) at 2.68 A resolution (PDB entry 5YUN). The inhibitor, myricetin, is
      a flavonol that possesses many pharmacological activities, such as anticancer,
      anti-inflammatory, and antibacterial properties, and is beneficial for humans.
      Four monomers of PaSSB and two of myricetins were found per asymmetric unit.
      Various interactions between myricetin and PaSSB were examined. Among these, four
      residues in PaSSB, Lys7, Arg62, Glu80, and Gly107 were found crucial for forming
      hydrogen bond to myricetin. These two myricetins occupy the grooves for ssDNA
      binding of SSB that may prevent ssDNA-wrapping and ssDNA-binding stably from SSB.
      In addition to explaining how SSB can be inhibited, the myricetin-SSB interaction
      modes in this paper may also provide insights into how myricetin can bind and
      inhibit proteins on cancer-signaling pathways.

PMID- 30213634
TI  - Depleting the carboxy-terminus of human Wnt5a attenuates collagen-induced
      arthritis in DBA/1 mice.
AB  - Wnt5a signalling plays pathological roles in synovial inflammation and bone
      destruction. In the present study, we designed four human Wnt5a-based DNA
      recombinants and detected their effects on immunogenicity and anti-rheumatism in
      a collagen-induced arthritis (CIA) model. Histomorphometry and micro-CT scanning
      showed that the phWnt5a-NL was superior to other recombinants because it resulted
      in decreased severity of arthritis, histopathological scores of synovial
      inflammation and bone erosion in CIA mice. In addition, ELISA and TRAP staining
      showed that the phWnt5a-NL-immunized CIA mice had reductions in the serum
      concentrations of the rheumatoid-associated cytokines IL-1beta and RANKL and in
      osteoclastogenesis. Furthermore, flow cytometry showed that the phWnt5a-NL
      treatment increased the percentage of Treg cells. Finally, western blotting
      analysis showed that the phWnt5a-NL-immunization interrupted beta-catenin and JNK
      expression in osteoclast precursors derived from the CIA mice. The results
      suggest that depleting the carboxy-terminus in hWnt5a-based DNA recombinants may
      be beneficial for the treatment of chronic inflammatory disorders involving bone
      resorption.

PMID- 30213635
TI  - Neuroprotective effects of levetiracetam, both alone and combined with
      propylparaben, in the long-term consequences induced by lithium-pilocarpine
      status epilepticus.
AB  - Status epilepticus (SE) is a neurological condition that frequently induces
      severe neuronal injury in the hippocampus, subsequent epileptogenesis and
      pharmacoresistant spontaneous recurrent seizures (SRS). The repeated
      administration of LEV (a broad-spectrum antiepileptic drug) during the post-SE
      period does not prevent the subsequent development of SRS. However, this
      treatment reduces SE-induced neurodegeneration in the hippocampus. Conversely,
      propylparaben (PPB) is a widely used antimicrobial that blocks voltage-dependent
      Na+ channels, induces neuroprotection and reduces epileptiform activity in vitro.
      The present study attempted to determine if the neuroprotective effects induced
      by LEV are augmented when combined with a sub-effective dose of PPB. Long-term SE
      induced consequences (hyperexcitability, high glutamate release, neuronal injury
      and volume loss) were evaluated in the hippocampus of rats. LEV alone, as well as
      combined with PPB, did not prevent the occurrence of SRS. However, animals
      treated with LEV plus PPB showed high prevalence of low frequency oscillations
      (0.1-4 Hz and 8-90 bands, p < 0.001) and low prevalence of high frequency
      activity (90-250 bands, p < 0.001) during the interictal period. In addition,
      these animals presented lower extracellular levels of glutamate, decreased rate
      of neurodegeneration and a similar hippocampal volume compared to the control
      conditions. This study's results suggest that LEV associated with PPB could
      represent a new therapeutic strategy to reduce long-term consequences induced by
      SE that facilitate pharmacoresistant SRS.

PMID- 30213636
TI  - Positive or negative emotion induced by feeding success or failure can affect
      behaviors, heart rate and immunity of suckling calves.
AB  - This study investigated behavioral and physiological responses of suckling calves
      to either positive or negative situations. Twelve healthy female suckling
      Holstein calves at approximately 30 days of age were randomly selected and
      allocated to two groups: a) a positive situation (POS) group that received a feed
      reward and b) a negative situation (NEG) group that experienced food frustration.
      Behavior, heart rate (HR), and immune parameters were measured during the emotion
      inducing periods and analyzed via ANOVA. The results indicated that the POS
      calves showed significantly increased locomotive play but decreased self
      grooming, head shaking, and tongue-rolling behaviors as compared to the NEG
      counterparts (p < .05). The NEG calves had the highest HR (p < .01) after
      negative emotion induction. Salivary cortisol (S-CORT) level significantly
      increased following both positive and negative emotional induction (p < .05). In
      humoral immunity, serum concentrations of IgA were not significantly affected by
      either the positive or negative situation (p > .05), but the salivary SIgA level
      of the POS calves was higher than that of the NEG group (p < .01). Serum IL-2 and
      IL-3 levels in the POS calves were significantly higher than those of the NEG
      group (p < .01). However, the serum TNF-alpha level in the POS group was
      significantly lower than in the NEG group (p < .05). The results suggest that
      hunger satiation or food frustration may induce different behavioral and
      physiological responses in suckling calves, presenting an interesting set of
      reactions appropriate in response to the emotional situations elicited by this
      short-term stimulus.

PMID- 30213637
TI  - An Unanticipated Airway Finding After Orotracheal Intubation With a GlideScope
      Videolaryngoscope.

PMID- 30213638
TI  - In Reply.

PMID- 30213639
TI  - Development and clinical consequences of white matter lesions in Fabry disease: a
      systematic review.
AB  - BACKGROUND: Fabry disease (FD) is a rare lysosomal storage disorder that might
      result in, amongst other complications, early stroke and white matter lesions
      (WMLs). More insight in WMLs in FD could clarify the role of WMLs in the disease
      presentation and prognosis in FD. In this systematic review we assessed the
      prevalence, severity, location and course of WMLs in FD. We also systematically
      reviewed the evidence on the relation between WMLs, disease characteristics and
      clinical parameters. METHODS: We searched Pubmed, EMBASE and CINAHL (inception to
      Feb 2018) and identified articles reporting on FD and WMLs assessed with MRI.
      Prevalence and severity were assessed for all patients combined and divided by
      sex. RESULTS: Out of 904 studies a total of 46 studies were included in the
      analyses. WMLs were present in 46% of patients with FD (581 out of 1276 patients,
      corrected mean age: 38.8 years, range 11.8-79.3) and increased with age. A total
      of 16.4% of patients (31 out of 189 patients, corrected mean age: 41.1 years,
      range 35.8-43.3 years) showed substantial confluent WMLs. Men and women showed
      comparable prevalence and severity of WMLs. However, men were significantly
      younger at time of WML assessment. Patients with classical FD had a higher chance
      on WMLs compared to non-classical patients. Progression of WMLs was seen in 24.6%
      of patients (49 out of 199 patients) during 38.1 months follow-up. Progression
      was seen in both men and women, with and without enzyme replacement therapy, but
      at an earlier age in men. Stroke seemed to be related to WMLs, but
      cerebrovascular risk factors, cardiac and renal (dys)function did not. Pathology
      in the brain in FD seemed to extend beyond the WMLs into the normal appearing
      white matter. CONCLUSIONS: A significant group of FD patients has substantial
      WMLs and male patients develop WMLs earlier compared to female patients. WMLs
      could be used in clinical trials to evaluate possible treatment effects on the
      brain. Future studies should focus on longitudinal follow-up using modern imaging
      techniques, focusing on the clinical consequences of WMLs. In addition, ischemic
      and non-ischemic pathways resulting in WML development should be studied.

PMID- 30213640
TI  - Quantitative assessment of cyanide in cystic fibrosis sputum and its oxidative
      catabolism by hypochlorous acid.
AB  - RATIONALE: Cystic fibrosis (CF) patients are known to produce cyanide (CN-)
      although challenges exist in determinations of total levels, the precise
      bioactive levels, and specificity of its production by CF microflora, especially
      P. aeruginosa. Our objective was to measure total CN- levels in CF sputa by a
      simple and novel technique in P. aeruginosa positive and negative adult patients,
      to review respiratory tract (RT) mechanisms for the production and degradation of
      CN-, and to interrogate sputa for post-translational protein modification by CN-
      metabolites. METHODS: Sputa CN- concentrations were determined by using a
      commercially available CN- electrode, measuring levels before and after addition
      of cobinamide, a compound with extremely high affinity for CN-. Detection of
      protein carbamoylation was measured by Western blot. MEASUREMENTS AND MAIN
      RESULTS: The commercial CN- electrode was found to overestimate CN- levels in CF
      sputum in a highly variable manner; cobinamide addition rectified this analytical
      issue. Although P. aeruginosa positive patients tended to have higher total CN-
      values, no significant differences in CN- levels were found between positive and
      negative sputa. The inflammatory oxidant hypochlorous acid (HOCl) was shown to
      rapidly decompose CN-, forming cyanogen chloride (CNCl) and the carbamoylating
      species cyanate (NCO-). Carbamoylated proteins were found in CF sputa, analogous
      to reported findings in asthma. CONCLUSIONS: Our studies indicate that CN- is a
      transient species in the inflamed CF airway due to multiple biosynthetic and
      metabolic processes. Stable metabolites of CN-, such as cyanate, or carbamoylated
      proteins, may be suitable biomarkers of overall CN- production in CF airways.

PMID- 30213641
TI  - How communication about risk and role affects women's decisions about birth after
      caesarean.
AB  - OBJECTIVE: This study investigated how health care provider communication of risk
      information, and women's role in decision-making, influenced women's preferences
      for mode of birth after a previous caesarean birth. METHODS: Women (N = 669) were
      randomised to one of eight conditions in a 2 (selectivity of risk information) *
      2 (format of risk information) * 2 (role in decision making) experimental design.
      After exposure to a hypothetical decision scenario that varied information
      communicated by an obstetrician to a pregnant woman with a previous caesarean
      birth across the three factors, women were asked to decide their preferred
      hypothetical childbirth preference. RESULTS: Women provided with selective
      information (incomplete/biased toward repeat caesarean) and relative risk formats
      (ratio of incidence being compared e.g. 2.5 times higher), perceived lower risk
      for caesarean and were significantly more likely to prefer repeat caesarean birth
      than those provided with non-selective information (complete/unbiased) and
      absolute risk formats (incidence rate e.g. 0.01 per 100). Role in decision-making
      did not significantly influence childbirth preferences CONCLUSIONS: Modifiable
      aspects of healthcare provider communication may influence women's decision
      making about childbirth preferences PRACTICE IMPLICATIONS: Optimised
      communication about risks of all options may have an impact on over-use of repeat
      CS.

PMID- 30213642
TI  - Tenacissoside H exerts an anti-inflammatory effect by regulating the nf-kappab
      and p38 pathways in zebrafish.
AB  - Marsdenia tenacissima exhibits biological activity with heat-clearing and
      detoxifying properties, relieving coughs and asthma and exerting anticancer and
      anti-HIV effects. Tenacissioside H (TH) is a Chinese medicine monomer extracted
      from the dried stem of Marsdenia tenacissima. We investigated the in vivo anti
      inflammatory activity of TH using three different zebrafish inflammation models:
      local inflammation induced by tail cutting, acute inflammation induced by CuSO4,
      and systemic inflammation induced by lipopolysaccharide (LPS). Real time
      polymerase chain reaction (RT-PCR) was used to elucidate the mechanism of TH
      action against LPS-induced inflammatory responses. Our results showed TH
      significantly reduced the number of macrophages in the injured zebrafish tail,
      inhibited CuSO4-induced migration of macrophages toward the neural mound, and
      decreased the distribution of macrophages in tail fin compared to LPS-treated
      group. Furthermore, TH inhibits LPS-induced inflammation responses in zebrafish
      by modulating the nuclear factor kappaB (nf-kappab) and p38 pathways to regulate
      inflammatory cytokines, such as tumor necrosis factor-alpha (tnf-alpha),
      cyclooxygenase (cox-2), interleukin-1b (il-1b), interleukin-8 (il-8), interleukin
      10 (il-10), nitric oxide synthase (nos2b) and prostaglandin E synthase (ptges).
      In conclusion, TH possesses anti-inflammation activity via the regulation of the
      nf-kappab and p38 pathways. This finding provides a reference for the clinical
      application of Xiaoaiping (the trade name of Marsdenia tenacissima extract).

PMID- 30213643
TI  - High glucose affected respiratory burst activity of peripheral leukocyte via G6PD
      and NOX inhibition in Megalobrama amblycephala.
AB  - High glucose levels are known to impair growth and immune function in fish. Here
      we investigated the role of glucose-6-phosphate dehydrogenase (G6PD) and NADPH
      oxidase (NOX) in high glucose-associated impairment of leukocyte respiratory
      burst activity in Megalobrama amblycephala. We cultured peripheral leukocytes
      isolated from M. amblycephala with media containing no glucose (non-glucose
      group), 11.1 mmol/L d-glucose (physiologic glucose group), 22.2 mmol/L d-glucose
      (high-glucose group), or 11.1 mmol/L d-glucose + 100 MUmol/L
      dehydroepiandrosterone (DHEA) (DHEA-treated group). After 24 h, we assayed
      production of reactive oxygen species (ROS) as a measure of respiratory burst
      function as well as activity of G6PD and NOX. The high-glucose group and DHEA
      treated group showed significantly reduced respiratory burst function, reduced
      production of ROS, and reduced G6PD and NOX activity at 24 h, compared to the non
      glucose and physiologic glucose groups (P < 0.05). The degree of impairment was
      similar between high-glucose and DHEA-treated groups (P > 0.05). These findings
      suggest that reduced NADPH availability likely underlies the suppression of
      respiratory burst function in M. amblycephala leukocytes exposed to high glucose
      levels.

PMID- 30213644
TI  - Anti-drug antibodies to LMB-100 are enhanced by mAbs targeting OX40 and CTLA4 but
      not by mAbs targeting PD1 or PDL-1.
AB  - LMB-100 is a recombinant immunotoxin being developed for cancer treatment that is
      composed of a Fab that binds to mesothelin and a portion of Pseudomonas exotoxin
      A. LMB-100 is in clinical trials for the treatment of mesothelioma and pancreatic
      cancer. To determine if check point modulating antibodies enhance the formation
      of anti-drug antibodies (ADA) against LMB-100, we treated mice with LMB-100 and
      four different immune modulating monoclonal antibodies that have different
      mechanisms of action; anti-CTLA4, anti-OX40, anti-PD-1 and anti-PDL-1. We found
      that anti-PD-1 and anti PDL-1 do not increase the formation of ADA, but anti-CTLA
      4 and anti-OX-40 do increase the onset of ADA. These results indicate that
      combining anti-CTLA-4 and anti-OX-40 with antibodies and other protein-based
      therapeutics may enhance ADA formation in humans.

PMID- 30213645
TI  - Corrigendum to "Interleukin-1beta, interleukin-1 receptor antagonist, interleukin
      6, interleukin-10, and tumor necrosis factor-alpha levels in CSF and serum in
      relation to the clinical diversity of Parkinson's disease" [Cell. Immunol. 327
      (2018) 77-82].

PMID- 30213646
TI  - Power in sports: A literature review on the application, assumptions, and
      terminology of mechanical power in sport research.
AB  - The quantification of mechanical power can provide valuable insight into athlete
      performance because it is the mechanical principle of the rate at which the
      athlete does work or transfers energy to complete a movement task. Estimates of
      power are usually limited by the capabilities of measurement systems, resulting
      in the use of simplified power models. This review provides a systematic overview
      of the studies on mechanical power in sports, discussing the application and
      estimation of mechanical power, the consequences of simplifications, and the
      terminology. The mechanical power balance consists of five parts, where joint
      power is equal to the sum of kinetic power, gravitational power, environmental
      power, and frictional power. Structuring literature based on these power
      components shows that simplifications in models are done on four levels, single
      vs multibody models, instantaneous power (IN) versus change in energy (EN), the
      dimensions of a model (1D, 2D, 3D), and neglecting parts of the mechanical power
      balance. Quantifying the consequences of simplification of power models has only
      been done for running, and shows differences ranging from 10% up to 250% compared
      to joint power models. Furthermore, inconsistency and imprecision were found in
      the determination of joint power, resulting from inverse dynamics methods,
      incorporation of translational joint powers, partitioning in negative and
      positive work, and power flow between segments. Most inconsistency in terminology
      was found in the definition and application of 'external' and 'internal' work and
      power. Sport research would benefit from structuring the research on mechanical
      power in sports and quantifying the result of simplifications in mechanical power
      estimations.

PMID- 30213647
TI  - Subject-specific calibration of neuromuscular parameters enables
      neuromusculoskeletal models to estimate physiologically plausible hip joint
      contact forces in healthy adults.
AB  - In-vivo hip joint contact forces (HJCF) can be estimated using computational
      neuromusculoskeletal (NMS) modelling. However, different neural solutions can
      result in different HJCF estimations. NMS model predictions are also influenced
      by the selection of neuromuscular parameters, which are either based on cadaveric
      data or calibrated to the individual. To date, the best combination of neural
      solution and parameter calibration to obtain plausible estimations of HJCF have
      not been identified. The aim of this study was to determine the effect of three
      electromyography (EMG)-informed neural solution modes (EMG-driven, EMG-hybrid,
      and EMG-assisted) and static optimisation, each using three different parameter
      calibrations (uncalibrated, minimise joint moments error, and minimise joint
      moments error and peak HJCF), on the estimation of HJCF in a healthy population
      (n = 23) during walking. When compared to existing in-vivo data, the EMG-assisted
      mode and static optimisation produced the most physiologically plausible HJCF
      when using a NMS model calibrated to minimise joint moments error and peak HJCF.
      EMG-assisted mode produced first and second peaks of 3.55 times body weight (BW)
      and 3.97 BW during walking; static optimisation produced 3.75 BW and 4.19 BW,
      respectively. However, compared to static optimisation, EMG-assisted mode
      generated muscle excitations closer to recorded EMG signals (average across hip
      muscles R2 = 0.60 +/- 0.37 versus R2 = 0.12 +/- 0.14). Findings suggest that the
      EMG-assisted mode combined with minimise joint moments error and peak HJCF
      calibration is preferable for the estimation of HJCF and generation of realistic
      load distribution across muscles.

PMID- 30213648
TI  - Between-session reliability of opto-electronic motion capture in measuring
      sagittal posture and 3-D ranges of motion of the thoracolumbar spine.
AB  - This study evaluated between-session reliability of opto-electronic motion
      capture to measure trunk posture and three-dimensional ranges of motion (ROM).
      Nineteen healthy participants aged 24-74 years underwent spine curvature, pelvic
      tilt and trunk ROM measurements on two separate occasions. Rigid four-marker
      clusters were attached to the skin overlying seven spinous processes, plus single
      markers on pelvis landmarks. Rigid body rotations of spine marker clusters were
      calculated to determine neutral posture and ROM in flexion, extension, total
      lateral bending (left-right) and total axial rotation (left-right). Segmental
      spine ROM values were in line with previous reports using opto-electronic motion
      capture. Intraclass correlation coefficients (ICC) and standard error of
      measurement (SEM) were calculated as measures of between-session reliability and
      measurement error, respectively. Retroreflective markers showed fair to excellent
      between-session reliability to measure thoracic kyphosis, lumbar lordosis, and
      pelvic tilt (ICC = 0.82, 0.63, and 0.54, respectively). Thoracic and lumbar
      segments showed highest reliabilities in total axial rotation (ICC = 0.78) and
      flexion-extension (ICC = 0.77-0.79) ROM, respectively. Pelvic segment showed
      highest ICC values in flexion (ICC = 0.78) and total axial rotation (ICC = 0.81)
      trials. Furthermore, it was estimated that four or fewer repeated trials would
      provide good reliability for key ROM outcomes, including lumbar flexion, thoracic
      and lumbar lateral bending, and thoracic axial rotation. This demonstration of
      reliability is a necessary precursor to quantifying spine kinematics in clinical
      studies, including assessing changes due to clinical treatment or disease
      progression.

PMID- 30213649
TI  - Articular-surface-based automatic anatomical coordinate systems for the knee
      bones.
AB  - Increasing use of patient-specific surgical procedures in orthopaedics means that
      patient-specific anatomical coordinate systems (ACSs) need to be determined. For
      knee bones, automatic algorithms constructing ACSs exist and are assumed to be
      more reliable than manual methods, although both approaches are based on non
      unique numerical reconstructions of true bone geometries. Furthermore,
      determining the best algorithms is difficult, as algorithms are evaluated on
      different datasets. Thus, in this study, we developed 3 algorithms, each with 3
      variants, and compared them with 5 from the literature on a dataset comprising 24
      lower-limb CT-scans. To evaluate algorithms' sensitivity to the operator
      dependent reconstruction procedure, the tibia, patella and femur of each CT-scan
      were each reconstructed once by three different operators. Our algorithms use
      principal inertia axis (PIA), cross-sectional area, surface normal orientations
      and curvature data to identify the bone region underneath articular surfaces
      (ASs). Then geometric primitives are fitted to ASs, and the ACSs are constructed
      from the geometric primitive points and/or axes. For each bone type, the
      algorithm displaying the least inter-operator variability is identified. The best
      femur algorithm fits a cylinder to posterior condyle ASs and a sphere to the
      femoral head, average axis deviations: 0.12 degrees , position differences: 0.20
      mm. The best patella algorithm identifies the AS PIAs, average axis deviations:
      0.91 degrees , position differences: 0.19 mm. The best tibia algorithm finds the
      ankle AS center and the 1st PIA of a layer around a plane fitted to condyle ASs,
      average axis deviations: 0.38 degrees , position differences: 0.27 mm.

PMID- 30213650
TI  - Engineering Saccharomyces cerevisiae for production of simvastatin.
AB  - Simvastatin is a semisynthetic cholesterol-lowering medication and one of the top
      selling statins in the world. Currently, industrial production of simvastatin
      acid (SVA) is a multistep process starting from the natural product lovastatin.
      For this reason, there is significant interest in direct production of
      simvastatin from a microbial host. In this study, six heterologous biosynthetic
      genes were introduced into Saccharomyces cerevisiae and the acyl-donor
      dimethylbutyryl-S-methyl mercaptopropionate (DMB-SMMP) was added, resulting in
      initial production of 0.5 mg/L SVA. Switching the yeast strain from JHY686 to
      BJ5464-NpgA increased total polyketide production to over 60 mg/L and conversion
      from dihydromonacolin L acid to monacolin J acid (MJA) was increased from 60% to
      90% by tuning the copy number of the P450 lovA. Increasing the media pH to 8.7
      led to a further 10-fold increase in SVA production. Optimized chemical lysis of
      the cell walls in situ after maximum MJA production led to 55 mg/L SVA titer,
      representing nearly complete conversion from MJA and a 110-fold increase in titer
      from the initial SVA production strain. The yeast strains developed in this work
      can be used as an alternative production method for SVA, and the strategies
      employed can be broadly applied for heterologous production of other fungal
      polyketides and semisynthetic compounds in yeast.

PMID- 30213651
TI  - Associations of abdominal intermuscular adipose tissue and inflammation: The
      Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: This study examined the associations between abdominal IMAT area and
      density with inflammatory markers associated with cardiometabolic disease.
      METHODS: 1897 participants enrolled in the Multi-Ethnic Study of Atherosclerosis
      underwent computed tomography to quantify body composition and measurements of
      adiponectin, leptin, interleukin-6 (IL-6), C-reactive protein (CRP), and
      resistin. RESULTS: The mean age and body mass index of participants was 65years
      and 28kg/m2, respectively, and 50% were female. After adjustment for age, sex,
      and race/ethnicity, as IMAT area increased and density decreased from the first
      to fourth quartile, markers of inflammation increased linearly (p<0.01). Using
      linear regression, and with adjustment for demographics, cardiovascular disease
      risk factors, and abdominal muscle area and density, a 1-standard deviation (SD)
      increase in total abdominal IMAT area was associated with a 21%, 36% and 20%
      higher IL-6, leptin, and CRP, respectively, and 19% lower adiponectin (p<0.001).
      With similar adjustment, a 1-SD decrease in total abdominal IMAT density was
      associated with a 14%, 32%, and 15% higher IL-6, leptin, and CRP, respectively,
      and 22% lower adiponectin (p<0.001). These associations were attenuated with the
      addition of visceral fat (p>0.05). CONCLUSIONS: Abdominal IMAT area and density
      are associated with inflammatory markers, with these associations attenuated by
      central adiposity.

PMID- 30213652
TI  - Antidepressant effect of repeated ketamine administration on kynurenine pathway
      metabolites in patients with unipolar and bipolar depression.
AB  - Ketamine has rapid antidepressant effects on treatment-resistant depression, but
      the biological mechanism underpinning this effect is less clear. Our aims were to
      examine whether kynurenine pathway metabolites were altered by six infusions of
      ketamine and whether these biological factors could act as potential biomarkers
      to predict ketamine's antidepressant effects. Six intravenous infusions of
      ketamine (0.5 mg/kg) were administered to 84 patients with unipolar and bipolar
      depression over a 12-d period. Symptom severity and response were assessed using
      the Montgomery-Asberg Scale (MADRS), and blood samples were collected at baseline
      and 24 h following the first infusion and at 24 h and 14 d after the sixth
      infusion (24 h, 13 d and 26 d). Blood samples from sixty healthy controls were
      collected for comparison with samples from the patients. Serum concentrations of
      tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) were measured by the
      liquid chromatography-tandem mass spectrometry method. At baseline, serum levels
      of TRP and KYNA and the KYNA/KYN ratio were lower and the KYN/TRP ratio was
      greater in depressed patients than in healthy controls. Overall, fifty (59.5%)
      patients responded to ketamine at 13 d. Ketamine responders had a greater KYNA
      level and KYNA/KYN ratio than nonresponders at 24 h and 13 d (all P < 0.05).
      Elevations in the KYNA levels and KYNA/KYN ratio at 24 h were significantly
      associated with reductions in MADRS scores at 24 h, 13 d and 26 d in the linear
      regression analysis (all P < 0.05). Our results showed a possible involvement of
      the kynurenine pathway in the rapid antidepressant effect of ketamine. Early
      changes in serum KYNA levels and the KYNA/KYN ratio could be potential predictors
      of antidepressanteffects of repeated ketamine administration.

PMID- 30213653
TI  - Snapshot summary of diagnosis and management of hepatocellular adenoma subtypes.
AB  - Hepatocellular adenomas (HCA) are rare benign hepatocellular tumors occurring
      mainly in women taking oral contraceptives with 2 major complications: severe
      bleeding and malignant transformation that can be avoided if nodules exceeding 5
      cm are resected. This simple attitude has been challenged in the recent years
      with HCA in men, in young adolescent, in aged persons, and complications in
      hepatocellular adenomas below 5 cm. The discovery of specific mutations leading
      to specific phenotypes has modified the clinical spectrum of the disease. The
      phenotypic immune classification of HCA based on the molecular classification is
      being widely used in liver referral centers. The aim of this snapshot is to
      briefly present for each subtype the clinical, pathological, immuno-pathological
      criteria as well as the risk of complications and guidelines for treatment and
      management.

PMID- 30213654
TI  - Correlations between stochastic epidemics in two interacting populations.
AB  - It is increasingly apparent that heterogeneity in the interaction between
      individuals plays an important role in the dynamics, persistence, evolution and
      control of infectious diseases. In epidemic modelling two main forms of
      heterogeneity are commonly considered: spatial heterogeneity due to the
      segregation of populations and heterogeneity in risk at the same location. The
      transition from random-mixing to heterogeneous-mixing models is made by
      incorporating the interaction, or coupling, within and between subpopulations.
      However, such couplings are difficult to measure explicitly; instead, their
      action through the correlations between subpopulations is often all that can be
      observed. Here, using moment-closure methodology supported by stochastic
      simulation, we investigate how the coupling and resulting correlation are
      related. We focus on the simplest case of interactions, two identical coupled
      populations, and show that for a wide range of parameters the correlation between
      the prevalence of infection takes a relatively simple form. In particular, the
      correlation can be approximated by a logistic function of the between population
      coupling, with the free parameter determined analytically from the
      epidemiological parameters. These results suggest that detailed case-reporting
      data alone may be sufficient to infer the strength of between population
      interaction and hence lead to more accurate mathematical descriptions of
      infectious disease behaviour.

PMID- 30213655
TI  - Effective cholangioscopic management of a patient with type IV Mirizzi syndrome.

PMID- 30213656
TI  - Cesarean delivery, preterm birth, and risk of food allergy: Nationwide Swedish
      cohort study of more than 1 million children.
AB  - BACKGROUND: Little is known about early-life risk factors for food allergy in
      children. OBJECTIVES: We examined the association between perinatal
      characteristics and future risk of food allergy in offspring. METHODS: This
      nationwide Swedish cohort study of 1,086,378 children born in Sweden in 2001-2012
      used prospectively recorded data from health care registers. Using Cox
      regression, we estimated hazard ratios (HRs) with 95% CIs for the association
      between perinatal characteristics (eg, cesarean delivery and preterm birth) and
      food allergy as defined by diagnoses in the National Patient Register, adjusting
      for infant sex and maternal factors (age at delivery, country of birth, parity,
      smoking, body mass index, and asthma/pulmonary disease). RESULTS: During the 13
      year follow-up, 26,732 (2.5%) children were given a diagnosis of food allergy.
      Food allergy was positively associated with cesarean delivery (HR, 1.21; 95% CI,
      1.18-1.25), large for gestational age (HR, 1.15; 95% CI, 1.10-1.19), and low 5
      minute Apgar score (HR, 1.22; 95% CI, 1.10-1.36) but negatively associated with
      very preterm birth (<32 weeks of gestation: HR, 0.74; 95% CI, 0.56-0.98). No
      association was found between food allergy and moderately preterm birth, low
      birth weight, or small for gestational age. Risk estimates were similar when the
      outcome was restricted to 2 records of diagnosed food allergy. In 1,000 children
      undergoing cesarean delivery, an extra 5 developed food allergy compared with the
      reference group, suggesting that 17% of food allergy in children born by means of
      cesarean delivery can be explained by this exposure (attributable fraction).
      CONCLUSIONS: Cesarean delivery was associated with increased risk of food
      allergy, whereas very preterm birth decreased risk.

PMID- 30213657
TI  - Xiaflex for Treatment of Peyronie's Disease.
AB  - Xiaflex or collagenase Clostridium histolyticum intralesional injections are safe
      and effective as first-line treatment for Peyronie's disease.

PMID- 30213658
TI  - What Conservation Does.
AB  - New agendas for conservation are regularly proposed based on the ground that
      existing strategies are overly pessimistic, restricted to biodiversity hotspots,
      and inappropriate to halt biodiversity loss. However, little empirical evidence
      supports such claims. Here we review the 12971 papers published in the leading
      conservation journals during the last 15 years to assess what conservation
      actually does. Although conservation research is affected by specific bias,
      conservation is playing a major role in providing empirical evidence of human
      impacts on biodiversity. Encouraging biodiversity comebacks are also published
      and a wide range of conservation tools, beyond the development of protected areas
      in wilderness areas, are promoted. We argue that finding new routes to
      conservation is neither necessary nor sufficient to halt biodiversity loss.

PMID- 30213659
TI  - Sustainable Biodiversity Databasing: International, Collaborative, Dynamic,
      Centralised.
AB  - The World Register of Marine Species (WoRMS) is a sustainable model of
      international collaboration around a centralised database that provides expert
      validated biodiversity data freely online. This model could be replicated for the
      over 1.2 million terrestrial and freshwater species to improve quality control
      and data management in biology and ecology globally.

PMID- 30213660
TI  - Let Scientific Writing Evolve, Not Stagnate.

PMID- 30213661
TI  - Nitrogen uptake potential under different temperature-salinity conditions:
      Implications for nitrogen cycling under climate change scenarios.
AB  - As projected by climate change models, increase in sea surface temperature and
      precipitation in the future may alter nutrient cycling in the coastal regions due
      to potential changes in phytoplankton community structure and their ability to
      assimilate nitrogen (N) and carbon (C). An experiment simulating different
      temperature and salinity conditions (28 degrees C-35 ambient conditions, 28oC-31,
      31oC-35 and 31oC-31) in mesocosms containing 1000 L of coastal water from the
      Arabian Sea was performed and N uptake rates were measured using 15N tracer
      technique on 2nd, 5th, 7th and 10th day of the experiment. The results show that,
      under all conditions, the total N (NO3- + NH4+) uptake rates were lower in the
      beginning and on the final day of the tracer experiment, while it peaked during
      middle, consistent with chlorophyll a concentrations. Total N uptake rate was
      significantly lower (p = 0.003) under ambient temperature-lower salinity
      condition (28oC-31) than the others. This indicates that lowering of salinity in
      coastal regions due to excessive rainfall in the future may affect the N uptake
      potential of the phytoplankton, which may change the regional C and N budget.

PMID- 30213662
TI  - Muscle-derived autologous mitochondrial transplantation: A novel strategy for
      treating cerebral ischemic injury.
AB  - The available evidence showed that mitochondrial transfer by releasing the
      extracellular vesicles containing mitochondria from astrocytes to neurons exerted
      a neuroprotective effect after stroke. Whether extracellular mitochondrial
      replenishment could rescue the tissues from cerebral ischemic injury still needs
      to be explored completely. It was hypothesized that the augmentation of
      mitochondrial damage after cerebral ischemia could be resolved by timely
      replenishment of exogenous mitochondria. A stroke model of middle cerebral artery
      occlusion (MCAO) was used in this study to verify this hypothesis. This study
      found that the number of extracellular mitochondria increased in rat
      cerebrospinal fluid after MCAO, and a higher proportion of mitochondria were
      associated with good neurological outcomes. Following 90-min ischemia,
      autologously derived mitochondria (isolated from autologous pectoralis major) or
      vehicle alone was infused directly into the lateral ventricles, and the rats were
      allowed to recover for 4 weeks. A plenty of infused mitochondria were found to be
      distributed in the boundary and ischemic penumbra areas. Furthermore, the
      transplantation of mitochondria reduced cellular oxidative stress and apoptosis,
      attenuated reactive astrogliosis, and promoted neurogenesis after stroke.
      Moreover, the transplantation of mitochondria decreased brain infarct volume and
      reversed neurological deficits. The findings suggested that the delivery of
      mitochondria through the lateral ventricles resulted in their widespread
      distribution throughout the brain and exerted a neuroprotective effect after
      ischemia-reperfusion injury.

PMID- 30213663
TI  - Frontal brain injury chronically impairs timing behavior in rats.
AB  - Traumatic brain injury (TBI) affects over 2.8 million people annually, and has
      been shown to increase motor impulsivity in both humans and animals. However, the
      root cause of this behavioral disinhibition is not fully understood. The goal of
      the current study was to evaluate whether timing behavior is disrupted after TBI,
      which could potentially explain increases in impulsive responding. Twenty-one
      male three-month old Long-Evans rats were trained on a fixed interval-18 s
      schedule. Following training, rats were placed on the Peak Interval Procedure,
      with intermittent peak trials. On peak trials, no behaviors were reinforced and
      response rates were recorded to determine timing ability. After reaching a stable
      baseline, rats received bilateral frontal TBI (n = 12) using controlled cortical
      impact or sham procedures (n = 9). After one week recovery, rats were re-assessed
      on the Peak Procedure for six weeks. An amphetamine challenge was carried out
      after behavior reached stable post-injury performance. TBI caused a chronic
      decrease/acceleration in peak time, increase in response variability, and
      reduction in response rate. The shifted peak time suggests that altered
      perception of time may contribute to impairments in response inhibition after
      TBI. Amphetamine significantly increased response variability, with TBI animals
      demonstrating greater sensitivity, but did not affect peak time in either group.
      These data suggest that timing may not be the sole factor explaining impulsive
      action after TBI given that amphetamine reduced motor impulsivity in prior
      studies. Further investigations will be needed to dissociate the effects of
      amphetamine on TBI with regard to timing behavior.

PMID- 30213664
TI  - Striatal dopamine and the temporal control of behavior.
AB  - Striatal dopamine strongly regulates how individuals use time to guide behavior.
      Dopamine acts on D1- and D2- dopamine receptors in the striatum. However, the
      relative role of these receptors in the temporal control of behavior is unclear.
      To assess this, we trained rats on a task in which they decided to start and stop
      a series of responses based on the passage of time and evaluated how blocking D1
      or D2-dopamine receptors in the dorsomedial or dorsolateral striatum impacted
      performance. D2 blockade delayed the decision to start and stop responding in
      both regions, and this effect was larger in the dorsomedial striatum. By
      contrast, dorsomedial D1 blockade delayed stop times, without significantly
      delaying start times, whereas dorsolateral D1 blockade produced no detectable
      effects. These findings suggest that striatal dopamine may tune decision
      thresholds during timing tasks. Furthermore, our data indicate that the
      dorsomedial striatum plays a key role in temporal control, which may be useful
      for localizing neural circuits that mediate the temporal control of action.

PMID- 30213665
TI  - Metapopulation model of rock-scissors-paper game with subpopulation-specific
      victory rates stabilized by heterogeneity.
AB  - Recently, metapopulation models for rock-paper-scissors games have been
      presented. Each subpopulation is represented by a node on a graph. An individual
      is either rock (R), scissors (S) or paper (P); it randomly migrates among
      subpopulations. In the present paper, we assume victory rates differ in different
      subpopulations. To investigate the dynamic state of each subpopulation (node), we
      numerically obtain the solutions of reaction-diffusion equations on the graphs
      with two and three nodes. In the case of homogeneous victory rates, we find each
      subpopulation has a periodic solution with neutral stability. However, when
      victory rates between subpopulations are heterogeneous, the solution approaches
      stable focuses. The heterogeneity of victory rates promotes the coexistence of
      species.

PMID- 30213666
TI  - The relationship between corticospinal tract integrity and lower-extremity
      strength is attenuated when controlling for age and sex in multiple sclerosis.
AB  - Muscle weakness, particularly in the lower-extremities, is common in multiple
      sclerosis (MS) and seemingly results from damage along white matter pathways in
      the central nervous system including the corticospinal tract (CST). This study
      examined CST structural integrity indicated by diffusion tensor imaging (DTI)
      related metrics (fractional anisotropy [FA], mean diffusivity [MD], radial
      diffusivity [RD], and axial diffusivity [AD]) as correlates of knee flexor (KF)
      and knee extensor (KE) muscle strength in MS. We included 36 persons with MS who
      underwent MRI and measurements of peak KE and KF strength using an isokinetic
      dynamometer. We examined associations using bivariate Spearman (rs) and partial
      Spearman correlation (prs) analyses controlling for age and sex. Peak KF strength
      was significantly associated with FA (rs = 0.42) and RD (rs = -0.36) and peak KE
      strength was significantly associated with MD (rs = -0.47) and RD (rs = -0.36).
      The correlations were attenuated after controlling for age and sex, but the
      relationship between KF strength and FA demonstrated a trend towards significance
      (prs = 0.33, p = 0.056). We provide evidence that the anatomical integrity of the
      CST may be associated with lower-extremity strength in MS. The attenuated
      correlations when controlling for age and sex suggest these factors, rather than
      MS per se, may be important contributors toward an association between CST DTI
      metrics and KF and KE strength. Future rehabilitation trials of resistance
      training should consider including CST integrity as an outcome and/or predictor
      of strength adaptations.

PMID- 30213667
TI  - Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues.
AB  - The progression of chronic liver diseases (CLD), irrespective of etiology,
      involves chronic parenchymal injury, persistent activation of inflammatory
      response as well as sustained activation of liver fibrogenesis and wound healing
      response. Liver fibrogenesis, is a dynamic, highly integrated molecular, cellular
      and tissue process responsible for driving the excess accumulation of
      extracellular matrix (ECM) components (i.e., liver fibrosis) sustained by an
      eterogeneous population of hepatic myofibroblasts (MFs). The process of liver
      fibrogenesis recognizes a number of common and etiology-independent mechanisms
      and events but it is also significantly influenced by the specific etiology, as
      also reflected by peculiar morphological patterns of liver fibrosis development.
      In this review we will analyze the most relevant established and/or emerging
      pathophysiological issues underlying CLD progression with a focus on the role of
      critical hepatic cell populations, mechanisms and signaling pathways involved, as
      they represent potential therapeutic targets, to finally analyze selected and
      relevant clinical issues.

PMID- 30213668
TI  - Nicotine improves probabilistic reward learning in wildtype but not alpha7 nAChR
      null mutants, yet alpha7 nAChR agonists do not improve probabilistic learning.
AB  - Cognitive impairments, e.g., reward learning, are present in various psychiatric
      disorders and warrant treatment. Improving reward-related learning could
      synergistically enhance psychosocial treatments and cognition generally. A
      critical first step is to understand the mechanisms underlying reward learning.
      The dopamine system has been implicated in such learning, but less known is how
      indirect activation of this system may affect reward learning. We determined the
      role of alpha7 nicotinic acetylcholine receptors (nAChR) on a probabilistic
      reversal learning task (PRLT) in mice that includes reward and punishment. Male
      alpha7 knockout (KO), heterozygous (HT), and wildtype (WT) littermate mice (n =
      84) were treated with vehicle, 0.03, or 0.3 mg/kg nicotine. Two cohorts of
      C57BL/6NJ male mice were treated with various alpha7 nAChR ligands, including the
      full agonists PNU282877 and AR-R-17779, the positive allosteric modulator CCMI,
      the partial agonist SSR180711, and the antagonist methyllycaconitine. All mice
      were then tested in the PRLT. Nicotine (0.3 mg/kg) significantly improved initial
      reward learning in alpha7 WT and HT mice but did not improve learning in KO mice,
      suggesting an involvement of the alpha7 nAChR in the pro-learning effects of
      nicotine. Neither alpha7 nAChR treatments (PNU282987, AR-R-17779, CCMI,
      SSR180711, nor methyllycaconitine) affected mouse PRLT performance however.
      Nicotine improved reward learning via a mechanism that may include alpha7 nAChRs.
      This improvement unlikely relied solely on alpha7 nAChRs however, since no alpha7
      nAChR ligand improved reward learning in normal mice. Future assessments of the
      effects of other nAChR subtypes on reward learning are needed.

PMID- 30213669
TI  - Continuous Inferior Vena Cava Diameter Tracking through an Iterative Kanade-Lucas
      Tomasi-Based Algorithm.
AB  - Ultrasound assessment of the respiratory-induced change in size of the inferior
      vena cava is a useful technique in the evaluation and management of critically
      ill patients. We have developed an automated technique based on the Kanade-Lucas
      Tomasi feature tracker and pyramidal segmentation to continuously track the
      diameter of the inferior vena cava during ultrasound. To test the accuracy of
      this automated process, the inferior vena cava of 47 spontaneously breathing
      patients were measured by trained ultrasound physicians and compared against the
      results obtained via the automated tracking. Good agreement between the
      techniques was found, with intra-class correlation coefficients for maximum
      vessel diameter, minimum diameter and caval index of 0.897, 0.967 and 0.975,
      respectively. More than 95% of the difference between physicians and automated
      measurements agreed to within 10% of the inferior vena cava collapse. Furthermore
      a phenomenon of cardiac collapsibility index variability was observed and
      reported. The accuracy and precision of this algorithmic technique provide a
      foundation for future automated measures for critical care ultrasound.

PMID- 30213670
TI  - Predicting ICU readmission using grouped physiological and medication trends.
AB  - BACKGROUND: Patients who are readmitted to an intensive care unit (ICU) usually
      have a high risk of mortality and an increased length of stay. ICU readmission
      risk prediction may help physicians to re-evaluate the patient's physical
      conditions before patients are discharged and avoid preventable readmissions. ICU
      readmission prediction models are often built based on physiological variables.
      Intuitively, snapshot measurements, especially the last measurements, are
      effective predictors that are widely used by researchers. However, methods that
      only use snapshot measurements neglect predictive information contained in the
      trends of physiological and medication variables. Mean, maximum or minimum values
      take multiple time points into account and capture their summary statistics,
      however, these statistics are not able to catch the detailed picture of temporal
      trends. In this study, we find strong predictors with ability of capturing
      detailed temporal trends of variables for 30-day readmission risk and build
      prediction models with high accuracy. METHODS: We study physiological
      measurements and medications from the Multiparameter Intelligent Monitoring in
      Intensive Care II (MIMIC-II) clinical dataset. Time series of each variable are
      converted into trend graphs with nodes being discretized measurements of each
      variable. Then we extract important temporal trends by applying frequent subgraph
      mining on the trend graphs. The frequency of a subgraph is a good cue to find
      important temporal trends since similar patients often share similar trends
      regarding their pathophysiological evolution under medical interventions.
      Important temporal trends are then grouped automatically by non-negative matrix
      factorization. The grouped trends could be considered as an approximate
      representation of patients' pathophysiological states and medication profiles. We
      train a logistic regression model to predict 30-day ICU readmission risk based on
      snapshot measurements, grouped physiological trends and medication trends.
      RESULTS: Our dataset consists of 1170 patients who are alive 30 days after
      discharge from ICU and have at least 12 h of data. In the dataset, 860 patients
      were not readmitted and 310 were readmitted, within 30 days after discharge. Our
      model outperforms all comparison models, and shows an improvement in the area
      under the receiver operating characteristic curve (AUC) of almost 4% from the
      best comparison model. CONCLUSIONS: Grouped physiological and medication trends
      carry predictive information for ICU readmission risk. In order to build
      predictive models with higher accuracy, we should add grouped physiological and
      medication trends as complementary features to snapshot measurements.

PMID- 30213671
TI  - Incorporation of Personality Typing into a Neurologic Surgery Residency Program:
      Utility in Systems Based Practice, Professionalism, and Self-Reflection.
AB  - BACKGROUND: In the neurosurgery residency, inherent personality traits can play a
      significant role in the adaptability and success of the resident physician.
      METHODS: The Myers-Briggs Type Indicator has been used extensively in the
      business and administrative world. As a quality improvement effort to promote
      self-reflection, personal and professional improvement among both faculty and
      resident members of a department of neurosurgery at a tertiary care academic
      medical center, a group learning exercise was implemented using the Myers-Briggs
      Type Indicator. RESULTS: All residents (11/11) and 85% of faculty (11/13)
      participated in the exercise. INTJ ("Mastermind," "Scientist") was the most
      commonly represented (36.4% compared with 2.1% in the general population; P <
      0.001). ENTJ ("Field Marshall," "Executive") was present in 18% compared with
      1.8% of the general population (P < 0.001). Thus, the 2 most common types (_NTJ)
      were present in 54.4% of our department compared with 3.9% of the general
      population (P < 0.001). CONCLUSIONS: Personality typing can be used to gain
      valuable insight into the composition of neurosurgery residency cohorts and
      resolve conflicts arising from personality differences within these groups as
      well as within the larger hospital setting.

PMID- 30213672
TI  - Prediction of Objectively Measured Physical Activity and Self-Reported Disability
      Following Lumbar Fusion Surgery.
AB  - OBJECTIVE: To investigate the predictive value of preoperative fear-avoidance
      factors (self-efficacy for exercise, pain catastrophizing, kinesiophobia, and
      depression), walking capacity, and traditional predictor variables for predicting
      postoperative changes in physical activity level and disability 6 months after
      lumbar fusion surgery in patients with chronic low back pain (LBP). METHODS: We
      prospectively enrolled 118 patients scheduled for lumbar fusion surgery for
      motion-elicited chronic LBP with degenerative changes in 1-3 segments of the
      lumbar spine. Associations between the predictors and the dependent variables
      were investigated with multiple linear regression analysis. Dependent variables
      were physical activity level as objectively measured with a triaxial
      accelerometer and disability as measured with the Oswestry Disability Index.
      RESULTS: Preoperative physical activity level (beta = -0.349; P < 0.001) and self
      efficacy for exercise (beta = 0.176; P = 0.021) were significant predictors of
      the postoperative change in physical activity. Preoperative disability (beta = 
      0.790; P < 0.001), self-efficacy for exercise (beta = 0.152; P = 0.024), and pain
      catastrophizing (beta = 0.383; P = 0.033) were significant predictors for the
      change in the Oswestry Disability Index. CONCLUSIONS: Patients with low levels of
      preoperative physical activity were more likely to increase their level of
      physical activity after lumbar fusion surgery, especially when their self
      efficacy for exercise was high. However, most of these patients still had low
      levels of physical activity after surgery, and they may therefore need extra
      support in increasing their postoperative physical activity levels.

PMID- 30213673
TI  - Posterior C2 fixation using trans-C2 inferior articular process screws: A case
      series and technical note.

PMID- 30213674
TI  - Intra- and Perioperative Complications Associated with Endoscopic Spine Surgery:
      A Multi-Institutional Study.
AB  - OBJECTIVE: To report on intra- and perioperative complications associated with
      working channel endoscopic spine surgery. METHODS: This study is a retrospective
      chart review of a multi-institutional patient cohort operated on by surgeons
      within the Endoscopic Spine Study Group between May 2010 and June 2017. RESULTS:
      Our study cohort consists of a total of 553 consecutive cases with an average age
      of 57 years. The most common procedure was an endoscopic discectomy (n = 377,
      68%) followed by foraminotomy (n = 156, 28.2%), unilateral laminotomy for
      bilateral decompression (n = 55, 9.9%), and lateral recess decompression (n = 29,
      5.2%). Overall, the rate of intra- and perioperative complications was 2.7%.
      There were 3 durotomies (0.54%), 2 epidural hematomas (0.36%), 2 patients
      developed a complex pain disorder (0.36%), 4 recurrent disc herniations within 3
      months (1.1%), 4 systemic complications (1.1%), and no wound infections. No risk
      factors were identified with regards to age, sex, approach, or number of
      segments. CONCLUSIONS: Endoscopic spine surgery is associated with a favorable
      rate of intra- and perioperative complications compared with reported rates of
      minimally invasive ortraditional open spine surgeries. Our report proposes safe
      and effective strategies for management of these complications.

PMID- 30213675
TI  - Quantitative Anterior Enlargement of the Spinal Canal by Anterior Controllable
      Antedisplacement and Fusion for the Treatment of Cervical Ossification of the
      Posterior Longitudinal Ligament with Myelopathy.
AB  - PURPOSE: This retrospective study aimed to investigate the effect of quantitative
      enlargement of spinal canal by anterior controllable antedisplacement and fusion
      (ACAF) for cervical ossification of the posterior longitudinal ligament (OPLL).
      METHODS: Forty-three patients with OPLL who underwent ACAF were enrolled.
      According to the use of a curvature ruler (CR), patients were divided into group
      A (CR used, n = 21) and group B (CR not used, n = 22). The average follow-up was
      9.5 months. The occupation rate (OR) of the spinal canal and the curvature of the
      cervical plate were recorded. The Japanese Orthopedic Association (JOA) scores
      were analyzed, and the recovery rate (RR) was calculated. Surgical complications
      were also investigated. RESULTS: The OR of the spinal canal in group A decreased
      from 66.7% +/- 12.8% to 19.1% +/- 10.9% after surgery (P < 0.05). In group B, the
      preoperative and postoperative OR was 63.9% +/- 11.7% and 21.2% +/- 8.7%,
      respectively (P < 0.05). Patients in group A had higher agreement of the
      curvature of the cervical plate between preoperative planning and postoperative
      measurement. The RR of JOA scores in group A was 73.7% +/- 19.7%, higher than in
      group B (70.9% +/- 7.3%, P > 0.05). Further comparison between the 2 groups,
      excluding those patients with OR <50%, showed that both JOA score and RR in group
      A were higher than in group B at the final follow-up (P < 0.05). CONCLUSIONS: The
      quantitative enlargement of the spinal canal by ACAF may provide a positive and
      favorable effect on enlarging the spinal canal and achieving better neurologic
      recovery for the treatment of cervical OPLL with myelopathy. CR can facilitate
      the achievement of better and more quantitative spinal canal enlargement.

PMID- 30213676
TI  - Post-Traumatic Pituitary Tumor Apoplexy After Closed Head Injury: Case Report and
      Review of the Literature.
AB  - BACKGROUND: Head trauma is a rare inciting factor of pituitary apoplexy (PA);
      however, there is a clear temporal relationship between trauma and apoplexy, and
      this is the first reported case of PA after an assault. CASE DESCRIPTION: We
      present a rare case of a 63-year-old man who developed PA after sustaining a
      closed head injury from assault with a metal pole. The patient had a known
      pituitary tumor for which he had previously declined surgical resection. On
      initial computed tomography scan, there was no traumatic intracerebral hemorrhage
      or subarachnoid hemorrhage. There was sellar expansion but no obvious sellar
      hemorrhage. Within 48 hours of admission, the patient was presumed septic after
      developing altered mental status, fevers, hypotension, and tachycardia. Magnetic
      resonance imaging of the brain with and without gadolinium revealed a poorly
      enhancing, necrotic, and hemorrhagic pituitary mass, consistent with pituitary
      tumor apoplexy. After administration of intravenous glucocorticoids, the patient
      underwent emergent endoscopic transsphenoidal resection of the pituitary tumor
      apoplexy. Postoperatively, the patient had neurologic improvement with stable
      vision. CONCLUSIONS: Early and accurate diagnosis is important to allow for
      timely neurosurgical intervention. Symptoms of fever, hypotension, and
      tachycardia in a patient with a known sellar mass should raise the suspicion of
      hypocortisolemia from pituitary tumor apoplexy.

PMID- 30213677
TI  - Surpass Flow Diverter in the Treatment of Ruptured Intracranial Aneurysms-A
      Single-Center Experience.
AB  - BACKGROUND: Use of a Surpass flow diverter (FD) device in the treatment of
      acutely ruptured aneurysm has not been well studied and reported in the
      literature. METHODS: We retrospectively reviewed patients with subarachnoid
      hemorrhage who were treated by Surpass FD placement at our hospital between June
      2016 and March 2018. Detailed analysis of medical records was performed to obtain
      patient age, gender, clinical history, Hunt and Hess grade, Fisher grade, results
      of radiographic and procedural details including technical success and
      complication, clinical outcome, and follow-up angiographic results. RESULTS: Our
      search identified 16 patients with 16 aneurysms who were treated with Surpass FD,
      of which 13 aneurysms (81%) were in the anterior circulation and 3 (19%) were in
      the posterior circulation. Aneurysm size ranged from 1.1 to 16 mm, with a mean of
      4 mm. The mean delay between subarachnoid hemorrhage and endovascular treatment
      was 5 days (range, 3-20 days). Only 1 Surpass FD was used in each patient,
      ranging in size from 3 * 25 mm to 4 * 50 mm. Fifteen patients (94%) achieved
      favorable clinical outcome (modified Rankin Scale score 0-1) at 3 months. One
      patient died of invasive fungal infection. Angiographic follow-up results were
      assessed by O'Kelly-Marotta grading scale in 15 surviving patients and showed a
      grade D result (no filling) in 13/15 aneurysms (87%) at 3 and 6 months.
      CONCLUSIONS: A Surpass FD device is a feasible option for the treatment of
      ruptured intracranial aneurysms that are difficult to treat by conventional
      clipping and coiling; however, larger and comparative studies with long-term
      follow-up are needed to confirm its safety and efficacy.

PMID- 30213678
TI  - Rare Case of Dumbbell-Shaped Spinal Cavernous Hemangioma and Literature Review.
AB  - BACKGROUND: Spinal epidural cavernous hemangiomas are rare vascular
      malformations. Exceptionally, they present with dumbbell-shaped morphology. When
      they happen, it's mandatory to include their pathology in the differential
      diagnosis because of their similarity to schwannomas. CASE DESCRIPTION: We report
      the case of a 72-year-old woman with a dumbbell-shaped thoracic epidural
      cavernous hemangioma. A literature review of diagnostic features and current
      treatment options are also discussed. CONCLUSIONS: Surgery is safe and effective
      in both improving patient condition and preventing acute hemorrhage that can
      worsen the outcome, causing neurologic and potentially irreversible deficits. The
      favorable result we obtained in our patient suggests that surgery should be
      evaluated as the first option, even in patients with large epidural cavernous
      hemangiomas.

PMID- 30213679
TI  - Attenuation of Proximal Junctional Kyphosis Using Sublaminar Polyester Tension
      Bands: A Biomechanical Study.
AB  - OBJECTIVE: To investigate the effect of sublaminar polyester tension bands on the
      biomechanics of the motion segments proximal to a long fusion construct. METHODS:
      This was a human cadaveric biomechanical study. Pure moments of 4 Nm and 8 Nm
      were applied to the native spine and the instrumented spine, respectively (n =
      8). The test conditions included native spine (T7-L2), fused (T10-L2), fused +
      bilateral tethers tensioned to 250 N at T9-T10 (tethers 250 N), fused + tethers
      tensioned to 350 N (tethers 350 N), fused (T11-L2) + tethers tensioned to 250 N
      at T9-T10 and 350 N at T10-T11 (2-level tethers), fused (T10-L2) + hand-tied
      suture loop through the spinous processes at T9-T10 (suture loop), and fused (T10
      L2) with the T9-T10 interspinous and supraspinous ligaments cut (cut ISL/SSL).
      RESULTS: The flexion range of motion (ROM) at T9-T10 of the fused spine, loaded
      at 8 Nm, increased to 162% of the native spine loaded at 4 Nm. The average
      flexion ROM at T9-T10 for tethers 250 N, tethers 350 N, 2-level tethers, suture
      loop, and cut ISL/SSL were 85% (P < 0.0001), 70% (P < 0.0001), 93% (P < 0.0001),
      141% (P = 0.13), and 177% (P = 0.66) of the native spine at 4 Nm, respectively (P
      values vs. fused). CONCLUSIONS: Sublaminar polyester bands can modulate the
      biomechanical flexion ROM as a function of the band pretension and provide a more
      consistent and tunable technique than hand-tying a suture loop between the
      spinous processes.

PMID- 30213680
TI  - Vagal Nerve Stimulation: Indications for Revision in Adult Refractory Epilepsy.
AB  - OBJECTIVE: The goal of this study was to assess the indications of revision for
      vagal nerve stimulation at a single institution in an adult population with drug
      resistant epilepsy. METHODS: This was a retrospective review of a prospectively
      collected database who underwent vagal nerve stimulator implantation for drug
      resistant epilepsy during 1992-2017. Patients receiving vagal nerve stimulation
      (VNS) implants were monitored throughout their perioperative and postoperative
      course and were classified according to type of seizure at the time of diagnosis
      and indications for VNS revision. In addition, response to dysfunctional VNS
      devices or adverse effects were noted. RESULTS: Most patients receiving VNS
      implants were given a diagnosis of complex partial seizures (CPSs) before
      implantation (95.1%). Other epileptic conditions identified requiring
      implantation included generalized seizures, generalized-atonic seizures, Lennox
      Gastaut syndrome, CPS or generalized seizures, and tuberous sclerosis (with
      generalized characteristics). High lead impedance was the most common indication
      for revision (5.6%), whereas device ineffectiveness leading to continued seizures
      was the most common indication for removal (2.3%). Infection, lead fracture, and
      dual- to single-pin lead battery changes occurred at an incidence of 1.9%,
      requiring either implant removal or revision. Other events that occurred, albeit
      rarely, included skin extrusion (0.5%), postoperative hematoma (0.5%), and
      implant rejection (0.5%) necessitating removal. CONCLUSIONS: VNS implantation in
      adults was shown to be a well-tolerated procedure. In addition, indications for
      revision or removal of the VNS device was low in this population with lead
      fracture rates lower than the incidence reported in pediatric population
      literature.

PMID- 30213681
TI  - Neurosurgical Residency Training in Latin America: Current Status, Challenges,
      and Future Opportunities.
AB  - BACKGROUND: This analysis provides an overview of neurosurgery residency programs
      in Latin America; it evaluates strengths, weaknesses, and limitations within the
      Latin American Federation for Societies in Neurosurgery countries. Considering
      the shared cultural background between these neighboring countries and
      globalization of neurosurgical education, similarities in training
      characteristics and equal opportunities are expected. However, program
      differences are inevitable and should be investigated to promote collaboration
      and homogenization of training. METHODS: A 39-item survey was distributed to 970
      neurosurgeons and residents in Latin America to assess aspects including working
      conditions, teaching, research, training, educational opportunities, and
      socioeconomics. RESULTS: In total, 276 neurosurgeons (28%) from 16 countries
      completed the survey. The average participant's age was 37 +/- 7 years, and the
      average duration of residency programs was 5 +/- 1 years. Trainees participated
      in around 5-10 cases during the typical 80-100 work hour week. Only 5% of survey
      respondents had a day off after a night shift, and 60% worked at least 3 night
      shifts per week. Only 34% had a mentorship program, Morbidity and mortality
      conferences were reported by 57% and research activities were compulsory in 45%.
      Satisfaction with evaluation methods was reported in 29%, although 96% reported
      satisfaction with their training programs overall. CONCLUSIONS: This study is the
      first of its kind to review neurosurgical training in Latin America's. Suggested
      areas of improvement include regulation of working hours, implementation of
      mentorship programs and standardized examinations, protected research time,
      increased support for conferences, and more opportunities for exchange rotations
      that will potentially bolster collaboration between programs.

PMID- 30213682
TI  - Automatic Intraoperative Correction of Brain Shift for Accurate Neuronavigation.
AB  - BACKGROUND: Unreliable neuronavigation owing to inaccurate patient-to-image
      registration and brain shift is a major problem in conventional magnetic
      resonance imaging-guided neurosurgery. We performed a prospective intraoperative
      validation of a system for fully automatic correction of this inaccuracy based on
      intraoperative three-dimensional ultrasound and magnetic resonance imaging-to
      ultrasound registration. METHODS: The system was tested intraoperatively in 13
      tumor resection cases, and performance was evaluated intraoperatively and
      postoperatively. RESULTS: Intraoperatively, the system was accurate enough for
      tumor resection guidance in 9 of 13 cases. Manually placed anatomic landmarks
      showed improvement of alignment from 5.12 mm to 2.72 mm (median) after
      intraoperative correction. Postoperatively, the limitations of the current system
      were identified and modified for the system to be sufficiently accurate in all
      cases. CONCLUSIONS: Automatic and accurate correction of spatially unreliable
      neuronavigation is feasible within the constraints of surgery. The current
      limitations of the system were also identified and addressed.

PMID- 30213683
TI  - Directing the nanoparticle formation by the combination with small molecular
      assembly and polymeric assembly for topical suppression of ocular inflammation.
AB  - In this paper, we presented a simple yet versatile strategy to generate a high
      drug payload nanoparticles by the combination with small molecular assembly and
      polymeric assembly for topical suppression of ocular inflammation. Upon physical
      mixing of the succinated triamcinolone acetonide (TA-SA) supramolecular hydrogel
      with the poly (ethylene glycol)-poly (E-caprolactone)-poly (ethylene glycol)
      (PECE) aqueous solution at 37  degrees C, TA-SA/PECE nanoparticles formed
      spontaneously and characterized thoroughly by transmission electron microscopy
      (TEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The
      formed TA-SA/PECE nanoparticles displayed a comparable in vitro anti-inflammatory
      efficacy to that of native triamcinolone acetonide (TA), through a significant
      downregulation of various proinflammatory cytokines levels (e.g., NO, TNF-alpha)
      in a lipopolysaccharide (LPS) actived RAW264.7 macrophage. Meanwhile, the
      enhanced transcorneal drug permeability of TA-SA/PECE nanoparticles over that of
      TA suspension was clearly observed in an isolated rabbit cornea. Intraocular
      biocompatibility test demonstrated that TA-SA/PECE nanoparticles presented good
      biocompatibility after topical instillation during entire study period. More
      importantly, the TA-SA/PECE nanoparticles displayed superior therapeutic efficacy
      over that of the TA suspension in the endotoxin-induced uveitis (EIU) rabbit
      model via decreasing neutrophil infiltration in anterior chamber. Overall, the
      proposed TA-SA/PECE nanoparticles might be a promising candidate for uveitis
      therapy.

PMID- 30213684
TI  - More than just caffeine: psychopharmacology of methylxanthine interactions with
      plant-derived phytochemicals.
AB  - In general, preparations of coffee, teas, and cocoa containing high levels of
      polyphenols, L-theanine and other bioactive compounds selectively enhance mood
      and cognition effects of caffeine. This review summarizes the bioactive
      components of commonly consumed natural caffeine sources (e.g. guayusa, mate and
      camellia teas, coffee and cocoa) and analyzes the psychopharmacology of
      constituent phytochemicals: methylxanthines, polyphenols, and L-theanine. Acute
      and chronic synergistic effects of these compounds on mood and cognition are
      compared and discussed. Specific sets of constituent compounds such as
      polyphenols, theobromine and L-theanine appear to enhance mood and cognition
      effects of caffeine and alleviate negative psychophysiological effects of
      caffeine. However, more research is needed to identify optimal combinations and
      ratios of caffeine and phytochemicals for enhancement of cognitive performance.

PMID- 30213685
TI  - S3I-201, a selective Stat3 inhibitor, restores neuroimmune function through
      upregulation of Treg signaling in autistic BTBR T+ Itpr3tf/J mice.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose symptoms
      include communication deficits, a lack of social skills, and stereotyped
      repetitive behaviors. We used BTBR T+ Itpr3tf/J (BTBR) mice, a model that
      demonstrates most of the core behavioral features of ASD, such as decreased
      sociability and high levels of repetitive behaviors. Currently, there is no
      treatment available that is able to improve most of the ASD disorder symptoms;
      thus, finding novel therapies is immediately required. Stat3 inhibitors are
      potential targets in the treatment of several immune disorders. The aim of the
      present study was to investigate the effects of S3I-201, a selective Stat3
      inhibitor, to determine its potential mechanism in BTBR mice. In this study, we
      first examined the effects of S3I-201 on repetitive behavior and marble burying.
      We also examined the treatment of S3I-201 on Th1 (IFN-gamma and T-bet), Th17 (IL
      17A, RORgammat, Stat3, IL-21, and IL-22), and T regulatory (Treg, Foxp3 and
      Helios) production in spleen CD4+ T cells. We further assessed Th1, Th17, and
      Treg mRNA and protein expression levels in brain tissues. S3I-201 treatment in
      BTBR mice significantly prevents marble burying and repetitive behavior.
      Furthermore, S3I-201 administration causes a considerable decrease in IFN-gamma,
      T-bet, IL-17A, RORgammat, Stat3, IL-21, and IL-22 levels, and increases in Foxp3
      and Helios production CD4+ T cells in BTBR mice. Additionally, S3I-201 treatment
      also significantly decreases Th1 and Th17 levels, and increases Treg mRNA and
      protein expression levels. Therefore, these results suggest that S3I-201 could be
      considered as a therapeutic option for ASD.

PMID- 30213686
TI  - Ligand-mediated dephosphorylation signaling for MAP kinase.
AB  - Extracellular signal-regulated kinase (ERK), also known as classical mitogen
      activated protein kinase, plays critical roles in cell regulation. ERK is
      activated through phosphorylation by a cascade of protein kinases including MEK.
      Various ligands activate the MEK/ERK pathway through receptor-dependent cell
      signaling. In cultured cells, many ligands such as growth factors, hormones,
      cytokines and vasoactive peptides elicit transient activation of MEK/ERK, often
      peaking at ~10 min after the cell treatment. Here, we describe a novel biological
      event, in which ligand-mediated cell signaling results in the dephosphorylation
      of MEK/ERK. Neuromedin N and neurotensin, peptides derived from the same
      precursor polypeptide, elicit cell signaling through the neurotensin receptors.
      In cultured human pulmonary artery smooth muscle cells (PASMCs), but not in human
      pulmonary artery endothelial cells (PAECs), we found that both neuromedin N and
      neurotensin promoted the dephosphorylation of ERK and MEK. Human PASMCs were
      found to express neurotensin receptor (NTR)-1, -2 and -3, while human PAECs only
      express NTR3. Neuromedin N-mediated dephosphorylation was suppressed by small
      chemical inhibitors of protein phosphatase 1/2A and peptidyl-prolyl isomerase.
      Transmission electron microscopy showed the formation of endocytic vesicles in
      response to neuromedin N treatment, and dephosphorylation did not occur when
      sorting nexin 9, a critical regulator of the endocytic vesicle formation, was
      knocked down. We conclude that neuromedin N and neurotensin elicit a unique
      dephosphorylation signaling in the MEK/ERK pathway that is regulated by
      endocytosis. Considering the pathophysiological importance of the MEK/ERK
      pathway, this discovery of the dephosphorylation mechanism should advance the
      field of cell signaling.

PMID- 30213687
TI  - Poly-gamma-glutamic acid suppresses osteoclastogenesis in human osteoclast
      precursors and prevents joint damage in a collagen-induced murine arthritis
      model.
AB  - Poly-gamma-glutamic acid (gamma-PGA), a natural polymer derived from Bacillus
      subtilis, shows anti-inflammatory activity. However, the effects of gamma-PGA on
      osteoclasts, which are important cells for joint destruction in inflammatory
      diseases such as rheumatoid arthritis (RA), have not yet been reported. In this
      study, we show that gamma-PGA markedly inhibits osteoclast differentiation in
      normal PBMC-derived osteoclast precursors and in synovial fluid macrophages of
      patients with RA. gamma-PGA also reduces RANK expression by down-regulating M-CSF
      receptors. Additionally, oral administration of gamma-PGA attenuated bone
      destruction in a collagen-induced arthritis (CIA) model, demonstrating decreases
      in inflammation, cartilage damage, and osteoclast formation in histological
      analyses. Taken together, these data suggest that gamma-PGA could be a good
      candidate for therapeutic prevention of joint destruction in RA.

PMID- 30213688
TI  - An epigenetic perspective on tumorigenesis: Loss of cell identity, enhancer
      switching, and NamiRNA network.
AB  - Various tumorigenic theories have been proposed in the past century, which
      contribute to the prevention and treatment of cancer clinically. However, the
      underlying mechanisms of the initiation of cancer, drug resistance, neoplasm
      relapse, and metastasis are still challenging to be panoramically addressed.
      Based on the abundant evidence provided by others and us, we postulate that Tumor
      Initiated by Loss of Cell Identity (LOCI), which is an inevitable initiating
      event of tumorigenesis. As a result, normal cells are transformed into the
      cancerous cell. In this process, epigenetic regulatory program, especially
      NamiRNA (Nuclear activating miRNA)-enhancer-gene activation network, is vital for
      the cell identity. The disorganization of NamiRNA-enhancer-gene activation
      network is a causal predisposition to the cell identity loss, and the altered
      cell identity is stabilized by genetic variations of the NamiRNA-enhancer-gene
      activation network. Furthermore, the additional genetic or epigenetic abnormities
      confer those cells to carcinogenic characteristics, such as growth advantage over
      normal cells, and finally yield cancer. In this review, we literally explain our
      tumor initiation hypothesis based on the corresponding evidence, which will not
      only help to refresh our understanding of tumorigenesis but also bring benefits
      to developing "cell identity reversing" based therapies.

PMID- 30213689
TI  - New developments in mechanisms of prostate cancer progression.
AB  - Prostate cancer is the most prevalent type of cancer in men. The etiology of
      prostate cancer development and the mechanisms underlying androgen-independent
      progression remains to be further investigated. There are many known targets for
      prostate cancer therapy including the androgen receptor (AR) axis, but resistance
      eventually develops in advanced disease suggesting the need to better understand
      mechanisms of resistance and consideration of multi-targeted therapy. Mechanisms
      contributing to resistance may include gene amplifications, gene mutations, AR
      splice variants, and changes in expression of androgen receptor co-regulatory
      proteins. Given the limitations of approved therapies, further study of
      additional potential targets is warranted. This review focuses on the roles of
      autophagy pathway, p62, Yes-associated protein (YAP), cancer stem cells, and
      epigenetics. Therapies targeting these potential mechanisms of resistance may
      interact with currently approved therapies either additively or synergistically.
      Thus, the study of combination therapy against multiple targets may be critically
      important to achieve more impact against lethal forms of prostate cancer
      resistant to all approved current therapies.

PMID- 30213690
TI  - The Mediterranean diet, fish oil supplements and Rheumatoid arthritis outcomes:
      evidence from clinical trials.
AB  - The impact of dietary interventions such as specific types of diet or nutritional
      supplements in rheumatoid arthritis (RA) has been subject to increased attention
      in recent years. The recognition of the unmet need to better understand the
      effects of specific dietary interventions on disease outcomes in RA, along with
      the growing patient interest on lifestyle interventions beyond pharmacotherapy,
      have informed the undertaking of this narrative literature review. The benefits
      of the Mediterranean Diet (MD) have been shown in various studies, although only
      a limited number of trials focus specifically on RA. Based on the studies
      reviewed, the MD may provide benefits in reducing pain and swollen and tender
      joints in RA patients. There is more and better evidence that n-3 polyunsaturated
      fat (PUFA) supplementation has the potential to reduce inflammation and provide
      clinical benefit, possibly slowing progression to pharmacotherapy. Yet, many of
      these studies to date are limited in their methodology; this being partly a
      reflection of the complexity of the research questions being addressed.
      Consequently, the conclusions that can be robustly drawn from their results are
      restricted. With a focus on clinical trials on the MD and fish oil
      supplementation, this review critically appraises the evidence, discussing the
      findings of studies in the wider context of impact on RA outcomes, methodological
      challenges, and practical points to consider as part of the routine care of RA
      patients.

PMID- 30213691
TI  - How can autoantibodies predict the long-term outcome of patients with
      interstitial lung disease? Results from a retrospective cohort study.
AB  - OBJECTIVES: This study aimed to investigate whether positive serum autoantibodies
      (AAbs) have any impact on survival and time evolution of radiological findings
      and pulmonary function indices in patients with interstitial lung disease (ILD).
      PATIENTS AND METHODS: Ninety four patients with regular clinical, functional and
      high resolution computed tomography (HRCT) imaging follow-up for at least 12
      consecutive months and complete testing for a panel of AAbs most commonly
      associated with ILD were enrolled in this retrospective two-center study.
      Eligible patients were divided into two groups based on the presence [ILD/AAb(+)]
      (n = 69) or absence [ILD/AAb(-)] (n = 25) of positive serum AAbs. All-cause
      mortality and longitudinal indicators of ILD progression such as a sustained
      decrease from baseline in absolute measurements of forced vital capacity (FVC) of
      >=10% or single-breath diffusion capacity (DLCOSB) of >=15% were the primary
      study endpoints. DLCOSB < 40% predicted on at least two consecutive measurements
      and progression of HRCT findings were our secondary endpoints. Kaplan-Meier (K-M)
      survival analysis and multivariate Cox proportional-hazards (PH) model were used
      to evaluate the prognostic significance of positive AAbs in the outcome of
      patients with ILD. RESULTS: ILD/AAb(+) patients were predominantly female (71% vs
      32%), were significantly younger (54.8 +/- 14.6 vs 66.8 +/- 10.1 years), and had
      longer duration of follow-up (78.1 +/- 53.1 vs 41.6 +/- 26.7 months), compared
      with ILD/AAb(-) patients (p < .01 for each comparison). Baseline measurements of
      FVC (% pred.) and DLCOSB (% pred.) did not differ significantly between the two
      groups. At the end of follow-up, mortality rates and the percentage of patients
      with a sustained FVC decrease were lower in the ILD/AAb(+) group (p < .05 for
      each comparison). With the exception of DLCOSB < 40% pred., ILD/AAb(+) patients
      had a longer median time-to-event for each of the other studied outcomes (p < .01
      for each K-M analysis). In addition, Cox PH models adjusted for age, smoking
      status, baseline pulmonary function tests and morphological pattern of ILD
      remained statistically significant in favor of the ILD/AAb(+) group (p < .05 for
      each comparison). CONCLUSIONS: AAb(+) patients with ILD seem to have a more
      favorable prognosis regarding all-cause mortality, long-term deterioration in
      lung function parameters and progression of HRCT findings than their AAb (-)
      counterparts.

PMID- 30213692
TI  - Nutritional recommendations for gout: An update from clinical epidemiology.
AB  - OBJECTIVE: To present the evidence for nutritional lifestyle changes recommended
      for gout patients; an explicit focus will be on the evidence for weight loss in
      overweight gout patients based on a recent systematic review and to describe
      methodological details for an upcoming weight loss trial. METHODS: We did a
      pragmatic but systematic search in MEDLINE for current guidelines that had made
      an attempt to make nutritional recommendations for gout. The quality of the
      evidence for the nutritional recommendations was evaluated based on the
      guidelines' own ratings and converted into a common simple version based on the
      GRADE system. The recently published systematic review on weight loss for gout,
      was based on six databases from which longitudinal studies that had quantified
      the effects following weight loss were included. The internal validity was
      assessed with the ROBINS-I tool and the quality of the evidence was assessed with
      the GRADE approach. Based on the results of the systematic review, a trial was
      designed, adhering to the principles of evidence based research. RESULTS: We
      included 17 guidelines. Most guidelines recommend avoiding or limiting alcohol
      intake (15; i.e. 88%), lose weight if relevant (12; 71%), and reduce fructose
      intake (11; 65%). The majority of the evidence for the nutritional
      recommendations was rated Moderate/Low or Very Low quality. Our recent systematic
      review on weight loss included 10 studies and found that the available evidence
      indicates beneficial effects of weight loss for overweight and obese gout
      patients, but the evidence is of low to moderate quality. As a consequence,
      researchers from the Parker Institute are launching a randomized trial to explore
      the short-term effects related to a diet-induced weight loss in obese gout
      patients. CONCLUSIONS: The nutritional recommendations for gout are generally
      based on low quality evidence. In terms of weight loss as a management strategy,
      the available evidence is in favor of weight loss for overweight/obese gout
      patients. However, since the current evidence consists of only a few studies
      (mostly observational) of low methodological quality, the Parker Institute are
      now initiating a rigorous exploratory randomized trial. Similar efforts are
      needed for other nutritional management strategies for gout.

PMID- 30213693
TI  - Impact of micronutrient deficiency & malnutrition in systemic sclerosis: Cohort
      study and literature review.
AB  - OBJECTIVES: The purpose of our study was to determine the prevalence and risk
      factors associated with malnutrition, and selenium (Se) and vitamin C (vitC)
      deficiencies in systemic sclerosis (SSc) patients. METHODS: We included adult SSc
      patients fulfilling the 2013 ACR/EULAR criteria from the Toulouse University
      Hospital cohort who underwent a micronutrient workup (including vitC, Se or
      thiamine levels) between 2011 and 2016. RESULTS: 82 patients were included,
      mostly women (76%), with a median age of 60 years. SSc was limited in 76% of the
      cases, with Scl-70 and centromere antibodies in 32% and 44%, respectively. Median
      disease duration was 7.4 years. Cardiac involvement was noticed in 19% and
      gastrointestinal tract in and 95%; 9% had pulmonary artery hypertension (PAH) and
      63% had interstitial lung disease. Overt malnutrition was present in 14 (17%)
      patients. Micronutrient deficiencies included Se (35%), vitC (31%) and/or
      thiamine (6%). Malnourished patients had significantly a higher summed Medsger
      disease severity scales (7.5 vs. 5, P = .003), lower hemoglobin (10.6 vs. 12.9
      g/dL, P < .0001) and vitC levels (3.6 vs. 10.6 mg/L, P = .003). Cardiac
      involvement was significantly associated with Se deficiency (OR 6.2, IC 95%[1.48
      32.70], P = .05). The factors associated with vitC deficiency were malnutrition
      (OR 8.57, IC 95%[2.16-43.39], P = .003), modified Rodnan skin score <= 14 (OR
      0.33, IC95[0.11-1], P = .05), PAH (27% in deficient vs. none in non-deficient
      patients, P = .0006) and esophagitis or Barrett's mucosa (OR 4.05, IC95[1.27
      13.54], P = .02). CONCLUSIONS: Se testing should be considered as soon as cardiac
      involvement is suspected. VitC testing should be considered in malnourished SSc
      patients, especially if skin involvement is extensive.

PMID- 30213694
TI  - Osteoarthritis and its management - Epidemiology, nutritional aspects and
      environmental factors.
AB  - Osteoarthritis (OA) is the most prevalent chronic rheumatic diseases worldwide,
      with a strong impact on individual and population health. OA is a clinically
      heterogeneous disease presenting with different clinical phenotypes recognising
      systemic and local risk factors. The pathogenesis is multifactorial including
      constitutive features of the joint, non-modifiable and modifiable risk factors.
      Epidemiological studies highlight the link between metabolic syndrome and OA and
      the effect of interplay between immunological and metabolic processes is getting
      increasing emphasis because of to the discovery that metabolic syndrome is
      implicated in OA pathogenesis and progression. In addition, recent findings
      suggest a potential role of dietary factors in susceptibility and progression of
      OA. In this review, we summarise the most robust evidence on epidemiology and
      classical risk factors OA, also exploring the most recent evidence on metabolic
      changes and Mediterranean diet for OA as a possible target to impact on the
      natural history of the disease.

PMID- 30213695
TI  - Are we really what we eat? Nutrition and its role in the onset of rheumatoid
      arthritis.
AB  - Accumulating research evidence suggests that individual dietary factors and
      dietary patterns might be implicated in the risk of development of rheumatoid
      arthritis (RA). This narrative review aims to present this evidence and provide
      nutritional recommendations for reducing RA risk in susceptible individuals.
      Overall, a 'Western' type diet rich in energy intake, total and saturated fat, an
      unbalanced ratio of n-3 to n-6 fatty acids, high in refined carbohydrates and
      sugar and low in fiber and antioxidants might increase the risk of RA both
      directly through increasing inflammation and indirectly through increasing
      insulin resistance and obesity, with the latter being a known risk factor for RA.
      On the contrary, consumption of long-chain omega-3 polyunsaturated fatty acids,
      derived from fish and fish oil, is associated with a reduced risk of RA probably
      due to their anti-inflammatory properties. The Mediterranean diet (MD), rich in
      plant-based foods such as wholegrains, legumes, fruit, vegetables, extra-virgin
      olive oil and low in red meat consumption, might have the potential to reduce the
      risk of RA. Based on current research evidence, it is suggested that adherence to
      the MD enhanced with an increased consumption of fatty fish, reduced consumption
      of sugar-sweetened drinks and maintenance of a normal body weight, contributes to
      reducing the risk of RA. Further research on RA susceptibility will allow for
      more specific dietary recommendations to be made.

PMID- 30213696
TI  - Autoimmune Hunger Games - a brief outline of the expanding role of nutrition in
      the aggravation and attenuation of autoimmune and rheumatic diseases.

PMID- 30213697
TI  - Food intolerance in patients with manifest autoimmunity. Observational study.
AB  - In the professional medical and scientific world, there is not many interest in
      the correlation of food intolerance and autoimmune diseases. However there is a
      lot of evidence that e.g. gluten or gliadine can induce autoimmmune diseases:
      example the interest in coeliac disease and autoimmunity. There is however a lot
      of informationavailable about leaky gut and autoimmunity. We performed an
      observational study in our data base;, where we selected 100 patients with
      manifest autoimmune disease with clear symptoms and autoimmune antibodies in the
      form of positive anf more tehn 160 titer. These patients were compared with 25
      control patients without any autoimmunity. We could clearly find a difference in
      food intolerance profiles when we compared AI patients with people without any
      AI. Overall there is a much greater reaction to several food epitopes, which can
      be observed on the level of specific antibodies tot he food epitopes. These igG
      levels for specific food antibodies are significantly higher in the patient group
      then in the control group. We can also see that some food epitopes provocate a
      very pronounced reaction, while other show no increased level of igG. Among the
      most reactive food epitopes are caseine, cow milk, wheat, gliadine, white of egg
      and rice. A variable reaction can bes een on nuts e.g.; walnuts and almonds.
      Almost no antibody reaction is noticed on vegetables, fish and meat products, who
      seem tob e immunologially very neutral. We conclude that food intolerance test is
      very important tool in patients with AI disease, and should be performed in each
      patient to tailor an individual diet program, which if properly followed, could
      relieve symptoms and probably stop or slow the the progression of the autoimmune
      disease. Also interesting for global research in AI disease is the fact that food
      is probably an important trigger for autoimmunity in vulnerable patients. More
      research on great scale and multicenter around this topic is mandatory and
      urgent.

PMID- 30213698
TI  - Probiotics and autoimmunity: Current evidence.

PMID- 30213699
TI  - The role of dietary sodium in autoimmune diseases: The salty truth.
AB  - Autoimmune diseases are a group of heterogeneous condition that occur secondary
      to the intrinsic loss of tolerance to self- antigens. In genetically susceptible
      individuals, the complex interplay of environmental factors and epigenetic
      deregulations have been proposed to drive disease etiopathogenesis. Various
      environmental variables have been identified including viral infections, exposure
      to pollutants, stress and dietary factors. Sodium, a major constituent of salt is
      essential for mammalian physiology. However, high salt intake may play a role in
      the development of autoimmune diseases. Several lines of evidence point toward
      the role of high sodium intake in reversing the suppressive effects of Regulatory
      T cells (Tregs) and instead promoting cellular shift toward T-helper (Th)-1 and
      Th17 pro-inflammatory phenotypes. These effects have been attributed to cascade
      of events that ultimately results in downstream activation of serum
      glucocorticoid kinase 1 (Sgk1). In vivo, various autoimmune animal models have
      confirmed the role of high sodium diet in the emergence and the exacerbation of
      autoimmune conditions including for instance Experimental Autoimmune
      Encephalomyelitis model for multiple sclerosis, MRL/lpr mouse model for lupus
      nephritis, collagen induced arthritis model for rheumatoid arthritis, and dextran
      sulfate sodium induced colitis, and TNBS-induced colitis models for Crohn's
      disease. Clinical epidemiological studies are scarce. High sodium intake was
      associated with increased risk of rheumatoid arthritis disease emergence. In
      multiple sclerosis, some studies suggest a relation to clinical exacerbation
      rates however other studies did not corroborate these results. Taken together,
      high dietary salt intake plays a role in the spectrum of autoimmune disease
      etiology. Further research is warranted to better characterize such relationship
      and assist in identifying individuals that would benefit from dietary salt
      restriction.

PMID- 30213700
TI  - Mechanistic immunological based classification of rheumatoid arthritis.
AB  - The classical autoimmunity paradigm in rheumatoid arthritis (RA) is strongly
      supported by immunogenetics suggesting follicular helper T-cell responses driving
      high titre specific autoantibodies that pre-dates disease onset. Using the
      immunological disease continuum model of inflammation against self with "pure"
      adaptive and innate immune disease at opposite boundaries, we propose a novel
      immune mechanistic classification describing the heterogeneity within RA.
      Mutations or SNPs in autoinflammatory genes including MEFV and NOD2 are linked to
      seronegative RA phenotypes including some so called palindromic RA cases.
      However, just as innate and adaptive immunity are closely functionally
      integrated, some ACPA+ RA cases have superimposed "autoinflammatory" features
      including abrupt onset attacks, severe attacks, self-limiting attacks, relevant
      autoinflammatory mutations or SNPs and therapeutic responses to autoinflammatory
      pathway therapies including colchicine and IL-1 pathway blockade. An emergent
      feature from this classification that non-destructive RA phenotypes, both innate
      and adaptive, have disease epicentres situated in the extracapsular tissues. This
      mixed innate and adaptive immunopathogenesis may be the key to understanding
      severe disease flares, resistant disease subsets that are unresponsive to
      standard therapy and for therapies that target the autoinflammatory component of
      disease that are not currently considered by expert therapeutic recommendations.

PMID- 30213701
TI  - New Methods for Disease Modeling Using Lentiviral Vectors.
AB  - Lentiviral vectors (LVs) transduce quiescent cells and provide stable integration
      to maintain transgene expression. Several approaches have been adopted to
      optimize LV safety profiles. Similarly, LV targeting has been tailored through
      strategies including the modification of envelope components, the use of specific
      regulatory elements, and the selection of appropriate administration routes.
      Models of aortic disease based on a single injection of pleiotropic LVs have been
      developed that efficiently transduce the three aorta layers in wild type mice.
      This approach allows the dissection of pathways involved in aortic aneurysm
      formation and the identification of targets for gene therapy in aortic diseases.
      LVs provide a fast, efficient, and affordable alternative to genetically modified
      mice to study disease mechanisms and develop therapeutic tools.

PMID- 30213702
TI  - Autotherapies: Enhancing Endogenous Healing and Regeneration.
AB  - The promise of tissue engineering and regenerative medicine to reduce the burden
      of disease and improve quality of life are widely acknowledged. Traditional
      tissue engineering and regenerative medicine approaches rely on generation of
      tissue constructs in vitro for subsequent transplantation or injection of
      exogenously manipulated cells into a host. While promising, few such therapies
      have succeeded in clinical practice. Here, we propose that recent advances in
      stem cell and developmental biology, immunology, bioengineering, and material
      sciences, position us to develop a new generation of in vivo regenerative
      medicine therapies, which we term autotherapies. Autotherapies are strategies
      based on optimizing endogenous tissue responses and capitalizing on manipulation
      of stem cell niches and endogenous tissue microenvironments to enhance tissue
      healing and regeneration.

PMID- 30213703
TI  - Response to: The Survival Time of 8376 Male Breast Cancer Patients.

PMID- 30213704
TI  - Survey on Adaptive Radiotherapy Practice.

PMID- 30213705
TI  - RADICAL(S) Radiotherapy Post-prostatectomy, Current and Future Practice.

PMID- 30213706
TI  - Applicability of Willems methods and Demirjian's four teeth method for dental age
      estimation: Cross sectional study on Tunisian sub-adults.
AB  - This study aims to evaluate and compare the applicability of three dental methods
      for age estimation, including Demirjian's four teeth, Willems I, and Willems II
      methods in a sample of Tunisian children. Panoramic radiographs of 500 children
      (241 females, 259 males) aged between 5 and 15 years were examined. The mean
      absolute error (MAE) was performed to assess the accuracy of age estimation.
      Independent samples t-test was employed to compare the differences, the
      chronological age minus dental age (CA-DA), between sexes for the three methods.
      All of the three methods underestimated the chronological age on the average, and
      almost for all age groups. The discrepancy between the chronological age and the
      estimated age was most frequently observed for ages above 8 years for all
      methods. In our study, the Demirjian's four teeth method underestimated the
      chronological age by 0.45 years for males and 0.32 years for females, with no
      significant difference (p=0.124). Whereas the Willems I method is indicted for
      underestimating the chronological age by 0.40 years for males, and by 0.69 years
      for females. Willems II method underestimated age by 0.91, and 0.64 years for
      males and females, respectively. It is established that the Demirjian's four
      teeth method was more accurate in estimating the dental age than the Willems I
      and II methods, with a mean absolute error of 0.76 years for males and 0.79 years
      for females (MAE=1.10, and 0.98 years for the Willems I/1.02, and 0.92 years for
      the Willems II). According to the results, it is highly recommended that the
      Demirjian's four teeth method should be applied when estimating the dental age in
      Tunisian males and females. In forensic cases, when the sex is unknown or
      doubted, the Willems II method could be appropriate.

PMID- 30213707
TI  - Re-assessment of South African juvenile facial soft tissue thickness data for
      craniofacial approximation: A comparative analysis using central tendency
      statistics.
AB  - Facial soft tissue thickness (FSTT) data form the basis of craniofacial
      identification methods such as facial approximation in cases where unknown
      skeletal remains lack unique identifiers such as fingerprints, DNA and dental
      records. Appropriate FSTT data are said to be required to produce accurate facial
      approximations that may be recognised by relatives. This view led to a vast
      number of studies considering subdivisions of FSTT data according to ancestry,
      age and sex. The paucity of South African juvenile FSTT standards of particular
      age groups, sex and ancestry is therefore problematic as "accurate" facial
      approximations cannot be produced. However, the use of pooled datasets and
      central tendency statistics offers a unique opportunity to circumvent the problem
      of small or absent FSTT datasets. The aim of this study was to use central
      tendency statistics of previously published South African data in order to assess
      whether it is necessary to subdivide FSTT datasets into different subgroups. In
      addition, a meta-analysis using central tendency statistics of 11 datasets within
      the C-table repository using the free open source TDStats programme (available
      through CRANIOFACIALidentification.com) for midfacial landmarks was performed.
      These datasets comprised of raw juvenile and adult FSTT data gathered from 1895
      to 2015 as measured by a variety of methods Scatter plots showed that FSTT
      correlation with age is rather weak, while Kernel density plots of FSTT by sex
      and landmark indicated no difference between South African juvenile males and
      females. In order to test the practical application of FSTT data, two facial
      approximations were constructed - one based on the shorth from South African data
      and C-tables and one based on an American dataset. When comparing the two facial
      approximations based on different datasets, geometric deviation indicated
      differences at midline and bilateral landmarks, but the visual presentation of
      the facial approximations was similar. Therefore it is suggested that differences
      of less than 3mm at any landmark do not result in profound practical differences
      in the juvenile face. Subcategorizing juvenile data is not necessary as the same
      result can be achieved by weighted means as presented in the sub-adult C-tables.

PMID- 30213708
TI  - New Evidence for Hypnozoite-Independent Plasmodium vivax Malarial Recurrences.
AB  - Information provided in recent, related papers has wide-ranging implications
      concerning, inter alia, the transmission of malaria, drug treatment, and
      eradication of the disease. Additionally, the research results represent support
      for the idea that recurrences of Plasmodium vivax malaria can arise from both
      liver hypnozoites and extravascular merozoites in bone marrow.

PMID- 30213709
TI  - Development of MS-based methods for identification and quantification of proteins
      altered during early pregnancy in dogs.
AB  - : Increased knowledge on serum protein profiles during early pregnancy in dogs
      would be valuable for several reasons, including animal welfare. Inflammatory
      changes during this period have been described. Today, mass spectrometry (MS) is
      a well-established technique to perform unbiased qualitative and quantitative
      studies of proteins in body fluids regardless of species. In the present study, a
      shotgun proteomic analysis based on nano-liquid chromatography-MS was performed
      to identify proteins of altered abundance during canine pregnancy, and,
      thereafter, a targeted parallel reaction monitoring (PRM)-method was developed
      and applied to absolutely quantify the concentrations of a selection of these
      proteins. Among the 32 proteins found altered between pregnant and non-pregnant
      dogs in the initial analysis, 12 were selected based on their changes in
      concentration and known biological importance, and these were analyzed using the
      PRM method. The PRM method showed good linearity, repeatability and sensitivity,
      and confirmed the higher concentration of Fibrinogen A, protein S alpha and C
      reactive protein at early time points in pregnant bitches. In conclusion, the
      combination of both methods allowed the identification of several altered
      proteins, and the quantification and description of the concentration patterns
      for a selection of them during the early stage of dog pregnancy. SIGNIFICANCE: MS
      is a powerful technique that allows the investigation of protein variations in
      samples from different origin, such as serum from dogs. The application of a
      shotgun proteomic analysis as a screening method has revealed the alteration of
      several proteins after fifteen days of pregnancy in dogs. The complementary
      development of a PRM MS-based method for several of these proteins has enabled
      the absolute quantification of their concentrations at five different time points
      during early pregnancy. With the MS technique, a combination of proteins can be
      studied with lower limits of detection than with immunoassays. Care should be
      taken not to interpret the observed changes in pregnant dogs as signs of disease.

PMID- 30213710
TI  - Association of treatment-achieved HbA1c with incidence of coronary artery disease
      and severe eye disease in diabetes patients.
AB  - AIM: To examine the association between treatment-achieved HbA1c values and
      incidence of both coronary artery disease (CAD) and severe eye disease with
      different diabetes treatments. METHODS: Associations of treatment-achieved HbA1c
      were investigated in various treatment groups [diet only; insulin; sulphonylurea
      (SU) alone; SU with glinides; and antihyperglycaemic agents other than glinides,
      SU or insulin] taken from a nationwide claims database of 14,633 Japanese
      diabetes patients. Cox's regression analysis examined risks over a 5.1-year
      follow-up. RESULTS: A significant linear trend was associated with HbA1c levels
      and CAD events in the diet-only group, and CAD risks were significantly higher in
      insulin and SU groups with HbA1c <= 7.0% and > 8.0% than in the diet-only group
      with HbA1c <= 7.0%. In contrast to CAD, a linear association was observed
      regardless of treatment modality between achieved HbA1c levels and risk of severe
      diabetic eye disease, but with no significant difference in eye disease risk
      between groups with HbA1c <= 7.0% and 7.1-8.0% in those treated with either SU
      alone, SU with glinides, or insulin. CONCLUSION: These findings suggest that the
      relationship between treatment-achieved HbA1c and incidence of both CAD and
      severe diabetic eye disease differed according to treatment, based on a large
      scale real-life database. More research is now needed to confirm these findings
      and to further investigate the underlying mechanisms.

PMID- 30213711
TI  - Avalanche Safety Practices Among Backcountry Skiers and Snowboarders in Jackson
      Hole in 2016.
AB  - INTRODUCTION: Carrying standard safety gear (beacon, probe, and shovel), planning
      a route of descent, and recreating with companions can help to mitigate the risk
      of injury or death resulting from avalanches in the backcountry. The goal of this
      study was to identify factors associated with performance of these safety
      practices. METHODS: A convenience sample of backcountry skiers and snowboarders
      was surveyed in 2016 at the backcountry gates of Jackson Hole Mountain Resort.
      Each participant was surveyed on characteristics including skill level, sex, age,
      prior avalanche education, and residency in the Jackson Hole area. Safety
      practices were also measured against avalanche hazard forecasts. Correlations
      were assessed using Fisher's exact testing. RESULTS: A total of 334 participants
      were surveyed. Factors associated with carrying avalanche safety gear included
      higher expertise, being a resident of the Jackson Hole area, and prior avalanche
      education. Factors associated with having a planned route of descent included
      higher expertise and being a resident of the Jackson Hole area. Factors
      associated with recreating with companions included younger age and lower
      expertise. Sex had no association with any of the surveyed safety practices.
      Participants were less likely to carry avalanche safety gear on low avalanche
      hazard days. CONCLUSIONS: Certain individual characteristics of backcountry
      skiers and snowboarders are associated with increased frequency of adherence to
      recommended safety practices. These findings suggest that particular categories
      of backcountry recreationists may benefit from further avalanche safety
      education. The results of this study could help direct future educational efforts
      among backcountry recreationists.

PMID- 30213712
TI  - Response to 'Cerebellum as a possible target for neuromodulation after stroke'.

PMID- 30213713
TI  - National Private Payer Coverage of Prostate MRI.
AB  - PURPOSE: To investigate the national coverage landscape for prostate MRI
      services, assessing the presence of updated and accurate coverage requirements by
      private payers. METHODS: The database Policy Reporter was used to evaluate
      private payer coverage related to prostate MRI for 81 plans covering 149 million
      people in the United States. Both the indications and requirements for prostate
      MRI coverage were recorded in a variety of clinical scenarios, including initial
      diagnosis, staging, active surveillance, and suspected recurrence. RESULTS:
      Overall, 11.1% of payers cover prostate MRI in biopsy-naive patients with
      suspected prostate cancer, with the remaining 88.9% requiring a prior negative
      biopsy. Nearly all payers also require either a rising prostate-specific antigen
      (PSA) or abnormal digital rectal examination (DRE). Rarely, a planned future MRI
      targeted biopsy serves as a basis for MRI coverage. Initial staging is covered by
      most payers, although typically with stringent indications (eg, PSA >= 20 ng/mL,
      Gleason score >=7 or 8, stage T3 or T4, or >=20% risk of nodal metastases). Only
      10 payers discuss active surveillance, with 8 of these requiring a repeat biopsy
      before MRI. Coverage for detection of post-treatment recurrence often requires a
      rising PSA or abnormal DRE, and occasionally only if a CT is first performed;
      only 10 of 81 payers address coverage after androgen deprivation treatment.
      CONCLUSION: Prostate MRI coverage varies widely among private payers, fails to
      recognize major clinical scenarios, is overly restrictive, and is often not
      reflective of current clinical practice. This creates challenges for patients and
      referring physicians seeking to obtain ready access to prostate MRI services.

PMID- 30213714
TI  - Patient-Friendly Summary of the ACR Appropriateness Criteria: Breast Implant
      Evaluation.

PMID- 30213715
TI  - Prolonged perioperative thoracic epidural analgesia may improve survival after
      cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for
      colorectal peritoneal metastases: A comparative study.
AB  - OBJECTIVE: To assess the effectiveness of prolonged perioperative thoracic
      epidural analgesia (PEA) on long term survival of patients who underwent a
      complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM). BACKGROUND:
      Grade III-IV morbidity affects long term outcomes after CRS and HIPEC. As
      compared with opioid administered via patient-controlled analgesia (PCA), PEA
      reduces morbidity. METHOD: From 2005 to 2016, 150 patients underwent CRS plus
      HIPEC with or without prolonged PEA. Clinical data and outcomes collected from
      prospective database were analyzed. Survival was assessed in terms of analgesic
      method using Kaplan-Meier plots and a propensity score. RESULTS: Patients
      'characteristics of 59 patients in PCA group were comparable to those of 91
      patients in PEA group, except for age, ASA score and fluid requirements,
      significantly more important in PEA group. Grade III-IV morbidity was 62.7% in
      PCA group compared with 36.3% in PEA group (p = 0.0015). Median overall survival
      (OS) of PEA group was 54.7 months compared to 39.5 months in PCA group (p =
      0.0078). When adjusted on the covariates, using the propensity score, the PEA
      significantly improves OS [HR 0.40 (95% CI: 0.28-0.56)] (p < 0.0001) and disease
      free survival (DFS) [HR 0.61 (95% CI: 0.45-0.81] (p < 0.0007) CONCLUSIONS: In
      this retrospective study of patients who underwent a complete CRS and HIPEC for
      colorectal peritoneal metastases, the perioperative thoracic epidural analgesia
      prolonged for over 72 h reduced significantly the grade III-IV morbidity and may
      improve OS and DFS.

PMID- 30213716
TI  - Introduction of minimally invasive surgery for distal and total gastrectomy: a
      population-based study.
AB  - BACKGROUND: Minimally invasive gastrectomy has been introduced in Western
      populations during the last decade. As minimally invasive distal gastrectomy
      (MIDG) versus total gastrectomy (MITG) are procedures with a different
      complexity, outcomes may differ. The aim of this population-based cohort study
      was to evaluate the safety of MIDG and MITG. MATERIALS AND METHODS: All patients
      who underwent potentially curative gastrectomy for gastric adenocarcinoma were
      included from the Dutch Upper GI Cancer Audit (2011-2016). Propensity score
      matching was applied to create comparable groups of patients receiving open
      distal gastrectomy (ODG) versus MIDG and open total gastrectomy (OTG) versus
      MITG, using patient and tumor characteristics. Postoperative outcomes and short
      term oncological outcomes were appraised. RESULTS: Of the 1970 eligible patients,
      1138 underwent distal gastrectomy and 832 underwent total gastrectomy. For distal
      gastrectomy, 390 ODG were matched to 288 MIDG patients. Although overall
      postoperative morbidity and mortality were similar, patients who underwent MIDG
      encountered less intra-abdominal abscesses (4% vs. 1%, p = 0.039) and wound
      complications (6% vs. 2%, p = 0.021). The median hospital stay was shorter after
      MIDGs (9 vs. 7 days, p < 0.001). For total gastrectomy, 323 OTG patients were
      matched to 258 MITG patients. Overall postoperative morbidity, mortality and
      hospital stay were similar, whereas the anastomotic leakage rate was higher after
      MITGs (11% vs. 17%, p = 0.030). Short-term oncological outcomes between both
      groups were equal for distal and total gastrectomy. CONCLUSION: Benefits of MIG
      during the early introduction were demonstrated for distal gastrectomy but not
      for total gastrectomy. An increased anastomotic leakage rate was encountered for
      MITG.

PMID- 30213717
TI  - Comparison of pelvic and para-aortic lymphadenectomy versus para-aortic
      lymphadenectomy alone for locally advanced FIGO stage IB2 to IIB cervical cancer
      using a propensity score matching analysis: Results from the FRANCOGYN study
      group.
AB  - INTRODUCTION: Pre-treatment evaluation of nodal status is crucial in women
      presenting with locally advanced cervical cancer (LACC). However, the prognostic
      impact of surgical staging remains to be proved, as published results comparing
      surgical versus radiological staging are contradictory. The aim of this study was
      to compare the prognosis of women with FIGO stage IB2-IIB CC who underwent
      surgical nodal staging including either exclusive para-aortic lymphadenectomy
      (PAL) or comprehensive pelvic + para-aortic lymphadenectomy (P-PAL). MATERIALS
      AND METHODS: Data of 314 women with FIGO stage IB2 to IIB CC treated between
      January 2000 and January 2015 were retrospectively abstracted from nine French
      institutions. The prognosis and outcomes were compared by Propensity score (PS)
      matching (PSM) analysis. RESULTS: The median follow-up was 33 months (2-114).
      When comparing women who underwent PAL vs P-PAL, the recurrence rates were 26%
      (37/144) and 28% (41/144), respectively (p = 0.595). The respective 3-year
      recurrence free survival (RFS) for P-PAL and PAL were 72.9% (95% CI, 65.7-81.0)
      and 70.7% (95% CI, 62.4-80.2), (p = 0.394). The respective 3-year overall
      survival (OS) rates for P-PAL and PAL were 86.8% (95% CI, 81.1-92.9) and 78.6%
      (95% CI, 70.4-87.7) (p = 0.592). In the sub-group of women with lymph node
      metastases, RFS was improved for women who underwent P-PAL compared to those with
      exclusive PAL (p = 0.027), with no difference in OS (p = 0.187). CONCLUSIONS:
      Comprehensive P-PAL does not seem to be of significant therapeutic benefit
      compared to exclusive PAL.

PMID- 30213718
TI  - Antimicrobial resistance, virulence gene profiles and molecular typing of
      Staphylococcus aureus isolates from dairy cows in Xinjiang, Northwest of China.
AB  - BACKGROUND: Staphylococcus aureus (SA) is one of the major pathogens causing
      dairy cow mastitis and endometritis. Recently, animal-derived SA strains have
      posed a serious threat to public health. However, little is known about
      antimicrobial resistance and virulence factors of SA strains isolated from dairy
      cows in Xinjiang China. Here, we characterized antimicrobial resistance,
      virulence gene profiles and genotypes of SA isolates from clinical mastitis and
      endometritis in dairy cows. METHODS: A total of 337 clinical samples (including
      186 milk samples from cases of clinical mastitis and 151 swab samples of
      endometritis) were collected from 15 large-scale dairy farms in Xinjiang China
      and screened for SA. All SA isolates were subjected to antimicrobial
      susceptibility testing, detection of virulence genes and molecular typing.
      RESULTS: A total of 155 strains of SA were isolated from 337 samples, in which 22
      strains were methicillin-resistant Staphylococcus aureus (MRSA) with a detection
      rate of 14.2%. The resistance of MRSA isolates was significantly higher than that
      of methicillin-sensitive SA (MSSA). Nevertheless, the percentage of different
      virulence genes varied between MSSA and MRSA. Staphylococcal Cassette Chromosome
      mec (SCCmec) typing showed that 155 strains could be divided into two genotypes:
      SCCmec I and SCCmec IVa. Agr typing identified three genotypes: Agr I, Agr II and
      Agr III. Spa typing identified four genotypes: t779, t2883, t13751 and t1939.
      MLST typing identified fourteen genotypes: ST188, ST294, ST9, ST805, ST2139, ST1,
      ST2700, ST903, ST2454, ST2990, ST63, ST968, ST2373 and STX, among which ST1 and
      ST9 had relatively high detection rates. CONCLUSIONS: The above findings revealed
      that ST9-t1939-Agr I was the main genotype of MSSA isolates, while ST1-SCCmec I
      t1939-Agr I was the main genotype of MRSA isolates from dairy cows. More
      significantly, STX was a novel genotype that was identified for the first time in
      this study. The fact that the majority of SA strains from dairy cows were
      multidrug resistant and carried multiple virulence genes may pose a potential
      risk to public health.

PMID- 30213719
TI  - Genomic analysis of the first isolate of KPC-2-producing Klebsiella pneumoniae
      from Uruguay.
AB  - OBJECTIVES: Since KPC-2-producing Klebsiella pneumoniae are associated with
      successful dissemination of a major clone, defined as sequence type 258 (ST258),
      the aim of this study was to perform whole-genome sequencing (WGS) of the first
      colistin-resistant K. pneumoniae strain (Kpn666) carrying blaKPC-2 identified in
      Uruguay in 2011 in order to identify genomic and phylogenetic traits. METHODS:
      WGS of strain Kpn666 isolated from an asymptomatic urinary tract infection was
      performed using Illumina MiSeq, and de novo assembly was performed using SPADES
      v.3.11. Contigs were re-ordered using the ST258 reference genome NJST258_1
      (GenBank CP006923) and were oriented with the MAUVE Contig Mover. Twenty complete
      genomes of K. pneumoniae identified as ST258 using the Pasteur MLST site were
      downloaded from GenBank (May 2017). A maximum-likelihood tree was created using
      MEGA7 based on core single nucleotide polymorphisms (SNPs) from whole-genome
      alignment obtained with SNP sites (https://github.com/sanger-pathogens/snp
      sites). RESULTS: WGS analysis revealed a genome of 5448179bp (5232 CDS, 108
      RNAs). Phylogenetic analysis identified that Kpn666 belonged to clade I lineage
      of ST258. Further studies also identified IncR, IncFIB(K) and IncFII(K) plasmid
      replicons and 11 transferable associated antimicrobial resistance genes (ARGs)
      comprising four drug classes. The mgrB gene involved in colistin resistance was
      shown to be disrupted by insertion of an IS5-like element. CONCLUSIONS: The first
      isolate of KPC-2-producing K. pneumoniae detected in Uruguay was sequenced and
      the results confirm the ability of this bacterium to capture several ARGs. The
      KPC-2 carbapenemase in Uruguay is likely to have been introduced by the high-risk
      clone ST258.

PMID- 30213720
TI  - Improved Survival of Elderly-fit Patients With Acute Myeloid Leukemia Requiring
      Intensive Therapy: 3-Year Multicenter Analysis From TALWG.
AB  - BACKGROUND: Elderly patients with acute myeloid leukemia (AML) have a poorer
      prognosis than younger ones. Several factors contribute to the poor outcomes for
      this patient group. PATIENTS AND METHODS: This study investigated the
      epidemiology, clinical characteristics, treatment, and clinical outcomes of
      elderly Thai patients with AML. This 3-year, prospective, multicenter study was
      focused on Thai patients with AML aged over 60 years who were diagnosed between
      2014 and 2016. RESULTS: Of 680 patients with AML, 235 elderly patients with AML
      (34.6%) were identified, with a mean age of 70 +/- 8 years. Using a 3-group
      cytogenetic risk classification (favorable, intermediate, and adverse risk), the
      proportions of patients in each category were 3.6%, 73.8%, and 22.6%,
      respectively. The median follow-up time for surviving patients was 846 days. The
      median overall survival (OS) of the patients was 128.2 days (range, 0-1205 days),
      with a 1-year OS of 13%. From a multivariate analysis, the significant factors
      associated with an improved long-term OS were patients with an Eastern
      Cooperative Oncology Group performance status 0 to 2 and those receiving
      intensive therapy. CONCLUSION: Our study confirms the high prevalence of AML in
      elderly patients with generally poor outcomes. Selected patients with a good
      performance status and those who received intensive induction treatment could
      have a long-term survival.

PMID- 30213724
TI  - Factor Xa inhibition by rivaroxaban regulates fibrogenesis in human atrial
      fibroblasts with modulation of nitric oxide synthesis and calcium homeostasis.
AB  - BACKGROUND: Rivaroxaban, a widely used factor Xa inhibitor in reducing stroke in
      atrial fibrillation (AF) patients has multiple biological effects with activation
      of protease-activated receptor (PAR) signaling. Atrial fibrosis plays a critical
      role in the pathophysiology of AF. In this study, we evaluated whether
      rivaroxaban regulates atrial fibroblast activity and its underlying mechanisms.
      METHODS AND RESULTS: Migration, proliferation analyses, nitric oxide (NO)
      production assay, calcium fluorescence imaging, and western blots were conducted
      in human atrial fibroblasts with or without rivaroxaban (100 nmol/L or 300
      nmol/L) and co-administration of L-NAME (L-NG-nitro arginine methyl ester, 100
      MUmol/L), EGTA (Ethylene glycol tetra-acetic acid, 1 mmol/L), thrombin (0.5
      U/mL), PAR1 agonist peptide (TFLLR-NH2, 100 MUmol/L), PAR1 inhibitor (SCH79797,
      0.5 MUmol/L) and PAR2 inhibitor (GB83, 10 MUmol/L). Atrial fibrosis was examined
      in isoproterenol (100 mg/kg, subcutaneous injection)-treated rats with or without
      rivaroxaban (10 mg/kg/day orally for 14 consecutive days). Rivaroxaban reduced
      the migration, pro-collagen type I production, and proliferation of atrial
      fibroblasts. Rivaroxaban decreased phosphorylated endothelial NO synthase (eNOS)
      (Thr 495, an inhibitory phosphorylated site of eNOS), and calcium (Ca2+) entry,
      and increased NO production. Moreover, L-NAME blocked the effects of rivaroxaban
      on fibroblast collagen and NO production. In the presence of EGTA, the migratory
      capability was similarly decreased in atrial fibroblasts with and without
      treatment with rivaroxaban (100 nmol/L), which suggests that rivaroxaban
      decreases migratory capability of atrial fibroblasts by inhibiting Ca2+ entry.
      Additionally, rivaroxaban significantly attenuated the effects of thrombin, and
      TFLLR-NH2 on migratory, proliferative, and pro-collagen type I production
      capability in atrial fibroblasts. SCH79797 or GB83 decreased pro-collagen type I
      production, migration, and proliferation capability in fibroblasts, but combined
      SCH79797 or GB83 with and without rivaroxaban had similar fibroblast activity.
      Moreover, rivaroxaban significantly decreased atrial fibrosis in isoproterenol
      treated rats. CONCLUSIONS: Rivaroxaban (100-300 nmol/L) regulates atrial
      fibroblast activity and atrial fibrosis by increasing NO production and
      decreasing Ca2+ entry through inhibition of PAR signaling.

PMID- 30213725
TI  - Opportunities and challenges for HIV self-testing in China.

PMID- 30213727
TI  - Phase Separation in Biology and Disease.

PMID- 30213726
TI  - A Sortase A Programmable Phage Display Format for Improved Panning of Fab
      Antibody Libraries.
AB  - Phage display of combinatorial antibody libraries is a versatile tool in the
      field of antibody engineering, with diverse applications including monoclonal
      antibody (mAb) discovery, affinity maturation, and humanization. To improve the
      selection efficiency of antibody libraries, we developed a new phagemid display
      system that addresses the complication of bald phage propagation. The phagemid
      facilitates the biotinylation of fragment of antigen binding (Fab) antibody
      fragments displayed on phage via Sortase A catalysis and the subsequent
      enrichment of Fab-displaying phage during selections. In multiple contexts, this
      selection approach improved the enrichment of target-reactive mAbs by depleting
      background phage. Panels of cancer cell line-reactive mAbs with high diversity
      and specificity were isolated from a naive chimeric rabbit/human Fab library
      using this approach, highlighting its potential to accelerate antibody
      engineering efforts and to empower concerted antibody drug and target discovery.

PMID- 30213728
TI  - What's in the "fold"?
AB  - Complexity in genome architecture determines how gene expression programs are
      established, maintained, and modified from early developmental stages to normal
      adult phenotypes. Large scale and hierarchical organization of the genome impacts
      various aspects of cell functions, ranging from X-chromosome inactivation, stem
      cell fate determination to transcription, DNA replication, and cellular repair.
      While chromatin loops and topologically-associated domains represent a basic
      structural or fundamental unit of chromatin organization, spatio-temporal
      organization of the genome further creates a complex network of interacting
      genome patterns, forming chromosomal compartments and chromosome territories. The
      understanding of human diseases, including cancers, auto-immune disorders,
      Alzheimer's, and cardiovascular diseases, relies on the associated molecular and
      epigenetic mechanisms. There is a growing interest in the impact of three
      dimensional chromatin folding upon the genome structure and function, which gives
      rise to the question "What's in the fold?" and is the main focus of this review.
      Here we discuss the principles determining the spatial and regulatory
      relationships between gene regulation and three-dimensional chromatin landscapes,
      and how changes in chromatin-folding could influence the outcome of genome
      function in healthy and disease states.

PMID- 30213729
TI  - Withaferin A inhibits apoptosis via activated Akt-mediated inhibition of
      oxidative stress.
AB  - Withaferin A (WFA), a withanolide derived from medicinal plant Withania
      somnifera, possesses anti-tumorigenic and immunomodulatory activities against
      various cancer cells. However, the role of WFA in myocardial ischemia reperfusion
      (MI/R) injury remains unclear. In the present study, we determined whether WFA
      may regulate cardiac ischemia reperfusion injury and elucidate the underlying
      mechanisms. We demonstrated that WFA enhanced H9c2 cells survival ability against
      simulated ischemia/reperfusion (SI/R) or hydrogen peroxide (H2O2)-induced cell
      apoptosis. In addition, the enhanced oxidative stress induced by SI/R was
      inhibited by WFA. Among the multiple antioxidant molecules determined,
      antioxidants SOD2, SOD3, Prdx-1 was obviously upregulated by WFA. When Akt
      inhibitor IV was administrated, WFA's suppression effect on oxidative stress was
      obviously abolished. Additional experiments demonstrated that WFA successfully
      inhibited H2O2 induced upregulation of SOD2, SOD3, and Prdx-1, ameliorated
      cardiomyocyte caspase-3 activity via an Akt dependent manner. Collectively, these
      results support the therapeutic potential of WFA against cardiac ischemia
      reperfusion injury and highlight the application of WFA in cardiovascular
      diseases holding great promise for the future.

PMID- 30213730
TI  - The suppressive effect of arsenic trioxide on TET2-FOXP3-Lyn-Akt axis-modulated
      MCL1 expression induces apoptosis in human leukemia cells.
AB  - Arsenic trioxide (ATO) has been reported to inhibit the activity of Ten-eleven
      translocation methylcytosine dioxygenase (TET). TET modulates FOXP3 expression,
      while dysregulation of FOXP3 expression promotes the malignant progression of
      leukemia cells. We examined the role of TET-FOXP3 axis in the cytotoxic effects
      of ATO on the human acute myeloid leukemia cell line, U937. ATO-induced apoptosis
      in U937 cells was characterized by activation of caspase-3/-9, mitochondrial
      depolarization, and MCL1 downregulation. In addition, ATO-treated U937 cells
      showed ROS-mediated inhibition of TET2 transcription, leading to downregulation
      of FOXP3 expression and in turn, suppression of FOXP3-mediated activation of Lyn
      and Akt. Overexpression of FOXP3 or Lyn minimized the suppressive effect of ATO
      on Akt activation and MCL1 expression. Promoter luciferase activity and chromatin
      immunoprecipitation assays revealed the crucial role of Akt-mediated CREB
      phosphorylation in MCL1 transcription. Further, ATO-induced Akt inactivation
      promoted GSK3beta-mediated degradation of MCL1. Transfection of constitutively
      active Akt expression abrogated ATO-induced MCL1 downregulation. MCL1
      overexpression lessened the ATO-induced depolarization of mitochondrial membrane
      and increased the viability of ATO-treated cells. Thus, our data suggest that ATO
      induces mitochondria-mediated apoptosis in U937 cells through its suppressive
      effect on TET2-FOXP3-Lyn-Akt axis-modulated MCL1 transcription and protein
      stabilization. Our findings also indicate that the same pathway underlies ATO
      induced death in human leukemia HL-60 cells.

PMID- 30213731
TI  - Assessment of the effects of transthyretin peptide inhibitors in Drosophila
      models of neuropathic ATTR.

PMID- 30213732
TI  - Increased bioavailability of cyclic guanylate monophosphate prevents retinal
      ganglion cell degeneration.
AB  - The nitric oxide - guanylyl cyclase-1 - cyclic guanylate monophosphate (NO-GC-1
      cGMP) pathway has emerged as a potential pathogenic mechanism for glaucoma, a
      common intraocular pressure (IOP)-related optic neuropathy characterized by the
      degeneration of retinal ganglion cells (RGCs) and their axons in the optic nerve.
      NO activates GC-1 to increase cGMP levels, which are lowered by cGMP-specific
      phosphodiesterase (PDE) activity. This pathway appears to play a role in both the
      regulation of IOP, where reduced cGMP levels in mice leads to elevated IOP and
      subsequent RGC degeneration. Here, we investigated whether potentiation of cGMP
      signaling could protect RGCs from glaucomatous degeneration. We administered the
      PDE5 inhibitor tadalafil orally (10 mg/kg/day) in murine models of two forms of
      glaucoma - primary open angle glaucoma (POAG; GC-1-/- mice) and primary angle
      closure glaucoma (PACG; Microbead Occlusion Model) - and measured RGC viability
      at both the soma and axon level. To determine the direct effect of increased cGMP
      on RGCs in vitro, we treated axotomized whole retina and primary RGC cultures
      with the cGMP analogue 8-Br-cGMP. Tadalafil treatment increased plasma cGMP
      levels in both models, but did not alter IOP or mean arterial pressure.
      Nonetheless, tadalafil treatment prevented degeneration of RGC soma and axons in
      both disease models. Treatment of whole, axotomized retina and primary RGC
      cultures with 8-Br-cGMP markedly attenuated both necrotic and apoptotic cell
      death pathways in RGCs. Our findings suggest that enhancement of the NO-GC-1-cGMP
      pathway protects the RGC body and axon in murine models of POAG and PACG, and
      that enhanced signaling through this pathway may serve as a novel glaucoma
      treatment, acting independently of IOP.

PMID- 30213733
TI  - Dichotomy between motor and cognitive functions of midbrain cholinergic neurons.
AB  - Cholinergic neurons of the pedunculopontine nucleus (PPN) are interconnected with
      all the basal ganglia structures, as well as with motor centers in the brainstem
      and medulla. Recent theories put into question whether PPN cholinergic neurons
      form part of a locomotor region that directly regulates the motor output, and
      rather suggest a modulatory role in adaptive behavior involving both motor and
      cognitive functions. In support of this, experimental studies in animals suggest
      that cholinergic neurons reinforce actions by signaling reward prediction and
      shape adaptations in behavior during changes of environmental contingencies. This
      is further supported by clinical studies proposing that decreased cholinergic
      transmission originated in the PPN is associated with impaired sensorimotor
      integration and perseverant behavior, giving rise to some of the symptoms
      observed in Parkinson's disease and progressive supranuclear palsy. Altogether,
      the evidence suggests that cholinergic neurons of the PPN, mainly through their
      interactions with the basal ganglia, have a leading role in action control.

PMID- 30213734
TI  - Construction and identification of the recombinant hFcepsilonRIalpha/RBL-2H3
      cells.
AB  - IgE/FcepsilonRI signal pathway plays a crucial role in triggering allergic
      reactions, and there is no cross-recognition between IgE and FcepsilonRI in human
      and rats. In order to obtain the hFcepsilonRIalpha/ RBL-2H3 cell line, total RNA
      was extracted from U937 cells, and the human FcepsilonRIalpha gene was obtained
      by RT-PCR technology. Then the amplified product was digested and inserted into
      the pIRES2-EGFP vector. After the plasmid was transfected into the RBL-2H3 cells
      using lipofectamine, and the RBL-2H3 cell lines of stable expression were
      screened by G418. The transfection efficiency reached 60.45% with optimizing
      transfection parameters. The last the expression of hFcepsilonRIalpha was
      detected by RT-PCR, western blotting and fluorescent microscopy. The present
      results demonstrated that the pIRES2-EGFP-hFcepsilonRIalpha vector was
      constructed and a stable cell line of hFcepsilonRIalpha/ RBL-2H3 cells was
      established successfully. This cell line is promising tools for further research
      on the pathogenesis and drug development of allergic diseases.

PMID- 30213735
TI  - Effects and Consequences of Being an OSCE Examiner in Surgery-A Qualitative
      Study.
AB  - OBJECTIVE: Even though objective structured clinical examination (OSCE) is a well
      investigated format for competency-based practical examination, only a few
      studies have explored the motivations of OSCE examiners and their opinions, both
      positive and negative, toward being an examiner. The aim of this study was to
      gain insights into the views of OSCE examiners using semi-structured interviews.
      DESIGN: Surgical OSCE examiners were queried at two medical faculties in Germany
      via semi-structured interviews. The interviews were transcribed verbatim and
      analyzed using the techniques of structured qualitative content analysis.
      SETTING: This study was conducted at the medical faculties of the Goethe
      University, Frankfurt, Germany and of the Otto-von-Guericke University,
      Magdeburg, Germany. PARTICIPANTS: All of the study participants were surgeons
      working at the university hospital of one of the faculties. RESULTS: A total of
      29 examiners were queried until a saturation of content was achieved. A critical
      reflection of one's own teaching was described as a major benefit by most
      participants. Furthermore, they noted that the standards and competences examined
      during the OSCE boosted the detail of their teaching sessions in the wards.
      However, the examiners criticized missed operations due the examination and were
      not appreciated by superiors for being an examiner. Most of the examiners (22/29)
      preferred to be an examiner themselves rather than appointing student peer
      examiners. If they had appointed someone else, that would mean they would miss
      valuable experiences useful for their own teaching. CONCLUSIONS: Being an OSCE
      examiner confers several advantages, notably the reflection of one's own
      teaching, which was described as highly valuable by the examiners.

PMID- 30213736
TI  - Questions Posed by Residents in the Operating Room: A Thematic Analysis.
AB  - OBJECTIVE: Questioning behavior is a type of intraoperative communication for
      which little information exists on the types of questions that residents ask. The
      purpose of this study is to describe and identify themes of questions asked by
      residents in the operating room. DESIGN: Trained observers documented questions
      asked by residents during operations. Thematic analysis was applied. SETTING:
      University of Utah Hospital (Salt Lake City, Utah) operating rooms;
      institutional. PARTICIPANTS: A total of 10 general surgical residents
      (postgraduate year 1 to 5) were observed along with 10 attending general
      surgeons. Cases were purposefully selected to be broadly representative of
      general surgery cases. RESULTS: Thematic saturation occurred following
      examination of 16 operative cases, which included 178 questions asked by
      residents. Two broad categories of questions emerged: case-related (71%) and
      noncase-related (29%), with multiple subcategories within the 2 groups. Case
      related subcategories included operative techniques, logistics, patient care, and
      other. Questions unrelated to the case included subcategories of social, work
      related but unrelated to case, other. Less than 1% of questions asked by
      residents during operations were reflective. CONCLUSIONS: Most questions related
      to the case were technical and most of those unrelated to the case were social;
      almost all questions were transactional in nature. Our identification of
      questioning themes by residents expands understanding of resident questioning
      behaviors, and therefore may enable residents and faculty to be more effective in
      establishing entrustment.

PMID- 30213737
TI  - The Effect of a Global Surgery Resident Rotation on Physician Practices Following
      Residency: The Mount Sinai Experience.
AB  - OBJECTIVE: The goal of the study was to evaluate the impact of Mount Sinai's
      international rotation on physician practices and attitudes following residency.
      DESIGN: An anonymous, retrospective study was conducted using an email survey.
      The initial survey was sent out in July 2015 with a second opportunity in
      September 2015. SETTING: Mount Sinai Hospital, New York City. PARTICIPANTS: All
      62 graduates of the Mount Sinai General and Plastic Surgery residencies who
      participated in the international rotation over the last 10 years. RESULTS: The
      primary outcome was level of involvement in service medicine with a secondary
      outcome examining participants views on the value of international rotations
      during residency. The response rate for the survey was 71% (44/62). Since leaving
      residency, 53% have been involved in one or more types of service medicine, 59%
      have been involved in at least one experience practicing medicine in an
      underserved area and 45% state that their current practice incorporates global
      surgery or service. 61% report that the rotation encouraged an interest in
      practicing in an underserved area and 44% (8/18) of those with no prior interest
      in global health reported that the rotation encouraged an interest. Respondents
      generally believe global health work could be rewarding (89%), provide
      opportunity for professional development (77%), and that residency should include
      global health electives (93%). CONCLUSIONS: Our results suggest that a mandatory
      global health rotation may encourage an interest in service medicine. Thus,
      program directors should continue to provide and encourage participation in
      international rotations during surgical residency.

PMID- 30213738
TI  - Examining the Impact of Using the SIMPL Application on Feedback in Surgical
      Education.
AB  - OBJECTIVE: The System for Improving and Measuring Procedural Learning (SIMPL)
      smartphone application allows physicians to provide dictated feedback to surgical
      residents. The impact of this novel feedback medium on the quality of feedback is
      unknown. Our objective was to compare the delivery and quality of best-case
      operative performance feedback given via SIMPL to feedback given in-person.
      DESIGN: We collected operative performance feedback given both in-person and via
      SIMPL from surgeons to residents over 6 weeks. Feedback transcripts were coded
      using Verbal Response Modes speech acts taxonomy to compare the delivery of
      feedback. We evaluated quality of feedback using a validated resident survey and
      third-party assessment form. SETTING: University of Wisconsin School of Medicine
      and Public Health, a large academic medical institution. PARTICIPANTS: Four
      surgical attendings and 9 general surgery residents. RESULTS: Nineteen SIMPL and
      18 in-person feedback encounters were evaluated. Feedback via SIMPL was more
      directive (containing thoughts, perceptions, evaluations of resident behavior, or
      advice) and contained more presumptuous utterances (in which the physician
      reflected on and assessed resident performance or offered suggestions for
      improvement) than in-person feedback (p = 0.01). The resident survey showed no
      significant difference between the quality of feedback given via SIMPL and in
      person (p = 0.07). The mean score was 47.74 (SD = 3.00) for SIMPL feedback and
      45.33 (SD = 4.77) for in-person feedback, with a total possible score of 50.
      Third-party assessment showed no significant difference between the quality of
      feedback given via SIMPL and in-person (p = 0.486). The mean score was 23.40 (SD
      = 3.75) for SIMPL feedback and 22.25 (SD = 5.94) for in-person feedback, with a
      total possible score of 30. CONCLUSIONS: Although feedback given via SIMPL was
      more direct and based on the attendings' perspectives, the quality of the
      feedback did not differ significantly. Use of the dictation feature of SIMPL to
      deliver resident operative performance feedback is a reasonable alternative to in
      person feedback.

PMID- 30213739
TI  - Introduction to Open Surgical Skills Curriculum: Randomized Trial of Self-Paced
      vs Group Video Tutorial Viewing.
AB  - OBJECTIVE: At our residency program, incoming interns are traditionally taught
      fundamental open surgical skills like suturing and knot tying in a group setting
      by viewing 12 instructional videos consecutively followed by individual baseline
      skill testing. We sought to evaluate if introduction to open surgical skills via
      self-paced viewing of video tutorials, as opposed to traditional group viewing,
      results in improved surgical skill acquisition in Obstetrics and Gynecology
      (OBGYN) interns as measured by higher proficiency score with decreased workload
      stress and anxiety. DESIGN, SETTING, PARTICIPANTS: A randomized control trial was
      conducted in which OBGYN PGY-1 residents in 2015 and 2016 (N = 35) were
      introduced to basic open surgical skills, such as knot tying and suturing, by
      viewing 12 video tutorials produced at UTSW (https://youtu.be/4w3hyL9muVU) for a
      surgical skills curriculum. Residents were randomized to 2 groups: group viewing
      vs self-paced viewing. Performance scores were calculated based on time and
      accuracy while workload and anxiety were measured by preand post-testing surveys
      using the National Aeronautics and Space Administration-Task Load Index and
      Spielberger State-Trait Anxiety Inventory 6 item questionnaires. RESULTS: There
      was no significant difference in proficiency score between the group vs self
      paced viewing in 8 out of 12 tasks using the Wilcoxon signed rank test (p >
      0.10). There was no statistically significant differences in workload stress
      based on the National Aeronautics and Space Administration-Task Load Index
      questionnaire (p = 0.399) or self-reported anxiety based on the Spielberger State
      Trait Anxiety Inventory 6 item questionnaire (p = 0.607). CONCLUSIONS: Contrary
      to recent educational data suggesting self-paced learning may improve outcomes,
      viewing instructional videos in a group setting continues to be a time efficient
      method to introduce basic open surgical skills to incoming OBGYN interns.

PMID- 30213740
TI  - Corrigendum to: Using the ACMGE Milestones as a Handover Tool From Medical School
      to Surgery Residency Journal of Surgical Education 2017 May-Jun;74(3):519-529.

PMID- 30213741
TI  - The Use of the Agatston Calcium Score in Predicting Carotid Plaque Vulnerability.
AB  - BACKGROUND: The use of the Agatston calcium scoring method has been described
      extensively in the coronary circulation, but to date, it has not been
      investigated in the extracranial carotid domain. We sought to evaluate this
      calcium scoring method in its ability to predict carotid plaque vulnerability.
      METHODS: We retrospectively reviewed all computed tomography angiogram studies of
      the carotid arteries performed between March 2012 and March 2017 at a single
      institution. We identified 68 consecutive patients with 99 internal carotid
      arteries who met criteria for review. Total calcium was quantified by the
      Agatston scoring method using the OsiriX software. Stenosis severity was
      determined using North American Symptomatic Carotid Endarterectomy Trial
      criteria. The relation between Agatston score and degree of stenosis was
      evaluated using the Spearman's Rho coefficient (R). RESULTS: Of 99 internal
      carotid arteries, 71 were asymptomatic and 28 were symptomatic. Baseline
      characteristics were comparable, with no significant difference in patient
      characteristics. There were significant differences in mean Agatston scores for
      asymptomatic versus symptomatic arteries (121.95 +/- 70.27 vs. 34.83 +/- 47.77, P
      = 0.0098, 50%-69% stenosis; 151.07 +/- 88.30 vs. 71.59 +/- 77.27, P = 0.0006, 70%
      99% stenosis). In both asymptomatic and symptomatic groups, Agatston calcium
      score increased as severity of stenosis increased. Higher Agatston score is
      protective against symptoms ipsilateral to the carotid lesion. CONCLUSIONS:
      Agatston calcium score may predict carotid plaque vulnerability, with higher
      scores associated with lower likelihood of developing symptoms ipsilateral to the
      carotid lesion. This score may be useful in predicting clinical behavior of
      carotid plaques.

PMID- 30213742
TI  - Effects of the Affordable Care Act on Vascular Patient Amputation Rates in
      Arkansas.
AB  - BACKGROUND: The Patient Protection and Affordable Care Act was signed into law in
      2010 and enacted in 2013 which improved insurance coverage across America due to
      increasing Medicaid eligibility as well as changes to individual insurance
      markets. In Arkansas, this was implemented by a Medicaid expansion waiver which
      allowed patients to purchase insurance with funds provided by the government to
      subsidize premiums through the marketplace. The goal of this study was to
      determine the effects of the Affordable Care Act (ACA) on Arkansas patients with
      peripheral arterial disease. METHODS: A pre-post research design using the
      Arkansas Hospital Discharge Dataset was used to study the impact of the ACA on
      limb amputation, distal bypass, discharge disposition, and total costs for
      patients diagnosed with peripheral arterial disease/atherosclerosis. The data
      were obtained for the years 2007 through 2009 (pre-ACA), 2011 through 2013 (post
      ACA), and 2014 through 2015 (post-Arkansas expansion). Bivariate analysis,
      analysis of variance, and regression analyses were performed to analyze the data.
      RESULTS: A total of 10,923 patients were identified. Uninsured patients ("self
      pay") decreased from 7% pre-ACA to 3.4% post-Arkansas expansion (P < 0.0001).
      There was a decrease in adjusted health-care costs after the Arkansas expansion
      (P < 0.0001). There was no change in mortality or transfer to rehabilitation
      facilities, but there was an increase in discharge to skilled nursing facilities
      along with a decrease in patients being discharged home (P < 0.0001). Regression
      analysis showed private insurance to be associated with a 49% reduction in the
      odds of an amputation (P < 0.0001). The Arkansas expansion was associated with a
      26% reduction in the odds of an amputation when compared with that before the ACA
      implementation (P < 0.005). Having private insurance was associated with a 26%
      increase in the odds of having a bypass when compared with uninsured patients (P
      < 0.05). CONCLUSIONS: Patients with private insurance have a decreased chance of
      amputation and increased odds of having a bypass when compared with patients who
      were of the self-pay category. The increase in private insurance coverage in our
      patient population could improve the rate of amputation in the vascular
      population in Arkansas by increasing early interventions for peripheral vascular
      disease.

PMID- 30213743
TI  - Jitterbug/Filamin and Myosin-II form a complex in tendon cells required to
      maintain epithelial shape and polarity during musculoskeletal system development.
AB  - During musculoskeletal system development, mechanical tension is generated
      between muscles and tendon-cells. This tension is required for muscle
      differentiation and is counterbalanced by tendon-cells avoiding tissue
      deformation. Both, Jbug/Filamin, an actin-meshwork organizing protein, and non
      muscle Myosin-II (Myo-II) are required to maintain the shape and cell orientation
      of the Drosophila notum epithelium during flight muscle attachment to tendon
      cells. Here we show that halving the genetic dose of Rho kinase (Drok), the main
      activator of Myosin-II, enhances the epithelial deformation and bristle
      orientation defects associated with jbug/Filamin knockdown. Drok and activated
      Myo-II localize at the apical cell junctions, tendon processes and are associated
      to the myotendinous junction. Further, we found that Jbug/Filamin co-distribute
      at tendon cells with activated Myo-II. Finally, we found that Jbug/Filamin and
      Myo-II are in the same molecular complex and that the actin-binding domain of
      Jbug/Filamin is necessary for this interaction. These data together suggest that
      Jbug/Filamin and Myo-II proteins may act together in tendon cells to balance the
      tension generated during development of muscles-tendon interaction, maintaining
      the shape and polarity of the Drosophila notum epithelium.

PMID- 30213744
TI  - Postoncological lacrimal duct reconstruction: A practical classification system
      for reconstructive planning and short-term results of a case series.
AB  - BACKGROUND: Surgical resection of skin tumors in the medial canthal area may
      damage the lacrimal duct and can result in chronic epiphora. Postoncologic
      reconstruction of the lacrimal duct has not been studied extensively. The current
      study discusses the anatomical and functional features of the lacrimal duct. It
      describes short-term functional outcomes after monocanalicular reconstruction of
      the lacrimal duct in a case series of 10 patients. METHODS: From February 2015 to
      October 2017, all patients with a postoncological lacrimal duct defect were
      analyzed to make an anatomical classification. The functional outcomes of
      patients after monocanalicular reconstruction were measured with the Munk scale
      up to 3 months after stent removal. RESULTS: Twelve patients had lacrimal duct
      defects after Mohs resection. Anatomical characteristics were used to create a
      clinical classification for lacrimal duct defects. This classification divides
      the upper (U) and lower (L) proximal lacrimal duct into two sections which can be
      damaged: the punctum and pars verticalis (1), the canaliculus horizontalis (2),
      or combined (3). The Common lacrimal duct (C) is the distal part of the lacrimal
      duct and can also be affected. Ten patients were analyzed after lacrimal duct
      reconstruction. Three months after stent removal, none of the patients suffered
      from epiphora. CONCLUSIONS: This article proposes an anatomical classification
      for lacrimal duct defects in the proximal lacrimal drainage system. The
      classification can be applied in comparing cases and determining reconstructive
      strategies after oncologic skin tumor resection. Short-term results are promising
      for future efforts to reconstruct the lacrimal duct.

PMID- 30213745
TI  - Breast imaging for aesthetic surgery: British Society of Breast Radiology (BSBR),
      Association of Breast Surgery Great Britain & Ireland (ABS), British Association
      of Plastic Reconstructive and Aesthetic Surgeons (BAPRAS).
AB  - This is an overview of the guidelines for breast imaging before and after
      aesthetic (cosmetic) breast surgery, which includes but is not limited to
      implants, lipomodelling and mammoplasty procedures. The guidelines are based on a
      review of the literature and consensus of breast imaging and aesthetic breast
      surgery specialists. 1. Pre-aesthetic surgery 2. Post-aesthetic surgery If breast
      imaging or breast assessment is required, it should be performed in a designated
      breast facility with access to specialist breast imaging and a complete breast
      multidisciplinary team in accordance with national guidelines and
      recommendations.

PMID- 30213746
TI  - Autologous fat grafting for enhancement of breast reconstruction with a
      transverse myocutaneous gracilis flap: A cohort study.
AB  - BACKGROUND: The transverse myocutaneous gracilis (TMG) flap is a viable option
      for the reconstruction of small- to moderate-sized breasts. The purpose of this
      series was to examine the outcomes of fat grafting to breast and donor site
      secondary to breast reconstruction with a TMG flap. METHODS: A cohort study was
      conducted to identify all patients who underwent autologous fat grafting after
      breast reconstruction with a TMG flap at two institutions between January 2009
      and October 2013. Data were collected regarding patient demographics, body mass
      index, and medical history as well as surgical details regarding TMG flap surgery
      and fat grafting. RESULTS: A total of 145 fat graftings were performed in 83
      patients following TMG flap breast reconstruction to improve the contour, shape,
      and volume of breasts (98%, n = 142), donor site (9%, n = 13) or both (7%, n =
      10), mainly after breast cancer surgery (83%). On average, 1.8 fat grafting
      sessions were performed with an average of 30cc fat per breast and 56.4cc fat per
      thigh. In 72% of patients, fat injection was performed by other pending
      reconstructive procedures. Fat was harvested by the tumescent technique, by using
      a filter syringe system, and injected without any further processing in multiple
      layers. CONCLUSIONS: Autologous fat grafting as a secondary procedure represents
      a powerful adjunct to enhance the aesthetic outcome of the reconstructed breast
      and donor site. It can be easily combined with other pending reconstructive
      procedures. With additional fat grafting, it may be possible to expand
      indications and offer autologous reconstruction with a TMG flap even in very lean
      patients.

PMID- 30213747
TI  - Beating uncontrolled eating: Training inhibitory control to reduce food intake
      and food cue sensitivity.
AB  - In our food-rich environment we must constantly resist appealing food in order to
      maintain a healthy lifestyle. Previous studies have found that food-specific
      inhibition training can produce changes in eating behaviour, such as a reduction
      in snack consumption. However, the mechanisms that drive the effect of inhibition
      training on eating behaviour remain unknown. Identifying the mechanism underlying
      food-specific inhibition training could lead to more targeted training
      interventions increasing the potential efficacy of such interventions. In the
      current study, we investigated directly whether training-induced effects on
      inhibitory control might underlie the predicted change in eating behaviour.
      Healthy individuals who scored high on uncontrolled eating were randomly assigned
      to receive six online training sessions over six consecutive days of either food
      specific response inhibition training (active group; n = 21) or response
      inhibition training without food stimuli (control group; n = 20). We measured pre
      and post-training inhibitory control in the context of food and food cue
      sensitivity, as well as food consumption in a bogus taste test. As expected, food
      specific inhibition training decreased snack consumption in the bogus taste test
      relative to control training. However, the active training did not improve
      inhibitory control towards food, nor did it reduce food cue sensitivity above and
      beyond the control training. Future studies are needed to investigate the
      potential underlying mechanism of food-specific inhibition training, as it
      remains unclear what drives the reliable effect on eating behaviour.

PMID- 30213748
TI  - Pathways of the relationships among eating behavior, stress, and coping in adults
      with type 2 diabetes: A cross-sectional study.
AB  - Stress is related to eating behavior, and eating behavior is important in
      diabetes treatment. The aim of this study was to examine the relationships among
      perceived stress, diabetes-related stress, coping strategies, and eating
      behaviors in adults living with type 2 diabetes (T2DM). Adults with type 2
      diabetes (n = 183) were recruited from a large metropolitan area in the Midwest
      United States. Stress factors and coping strategies associated with eating
      behaviors were measured using validated questionnaires. Structural equation
      modeling was used to investigate the relationships among perceived stress,
      diabetes-related stress, coping strategies, and eating behaviors. The final model
      showed that emotion-oriented coping partially mediated the effect of stress on
      eating behaviors. Specifically, emotion-oriented coping partially mediated the
      effect of diabetes-related stress on restrained eating behavior (r = 0.318, p <
      .001) and emotional eating behavior (r = 0.399, p < .001); emotion-oriented
      coping partially mediated the effect of perceived stress on external eating
      behavior (r = 0.276, p < .001). Emotion-oriented coping was found to be a partial
      mediator in the path model between stress and eating behaviors in people with
      type 2 diabetes. Knowledge of the association of stress with eating behaviors may
      prove important for health care providers in treatment and care of people with
      type 2 diabetes.

PMID- 30213749
TI  - Sweetness but not sourness enhancement increases acceptance of cucumber and green
      capsicum purees in children.
AB  - For children it is important to consume enough vegetables to establish healthy
      dietary patterns. Taste acceptance is an important factor contributing to food
      choice and consumption. Sweetness and sourness enhancement can increase
      acceptance of specific foods in children. The aim of this study was to determine
      the effect of sweetness and sourness enhancement on acceptance of cucumber and
      green capsicum purees in 5-6-year-old children. Three concentrations of sucrose
      (2, 5 and 10%) and citric acid (0.05, 0.08 and 0.15%) were added to cucumber and
      green capsicum purees. Children (n = 70, 5.7 +/- 0.5 yrs) assessed acceptance of
      the vegetable purees using a 5-point hedonic facial scale. Sweetness enhancement
      significantly increased acceptance of cucumber purees (5 and 10% sucrose) and
      green capsicum purees (2 and 10% sucrose) compared to unmodified purees. Sourness
      enhancement (0.05, 0.08 and 0.15% citric acid) did not significantly influence
      acceptance of cucumber and green capsicum purees compared to unmodified purees.
      Children differed in acceptance of vegetable purees with added sucrose and citric
      acid. Sweetness likers (cucumber 77.1%, green capsicum 58.6%) accepted sucrose
      concentrations better than sweetness non-likers in both vegetables. Sourness
      likers (cucumber 50.0%, green capsicum 44.3%) accepted medium and high
      concentrations of citric acid better than sourness non-likers in cucumber and all
      citric acid concentrations in green capsicum. We conclude that enhancement of
      sweetness increases acceptance of cucumber and green capsicum purees in most
      children whereas enhancement of sourness is better accepted by only a few
      children. This study highlights the challenge to get children to better accept
      vegetables, since only sweetness enhancement improved acceptance while addition
      of sucrose is undesirable. For a small subset of children enhancing sourness
      might be an alternative strategy to increase acceptance of vegetables.

PMID- 30213750
TI  - Cancer Stem Cells, CD44, and Outcomes Following Chemoradiation in Locally
      Advanced Cervical Cancer: Results From a Prospective Study.
AB  - PURPOSE: Although cancer stem cells (CSCs) have been reported across solid
      tumors, there is a dearth of data regarding CSC and its impact on outcomes of
      cervical cancer. METHODS AND MATERIALS: From October 2013 to December 2015,
      patients with squamous cancer of the cervix (stage IB2-IVA) were included.
      Pretreatment and posttreatment biopsy was obtained and immunohistochemistry was
      performed for SOX-2, OCT-4, Nanog, CD44, and Podoplanin. All patients received
      concurrent radiation and brachytherapy to an equivalent dose of 80 to 84 Gy to
      point A with concurrent weekly cisplatin. Correlation of CSC expression was
      performed with known prognostic factors. The effect of stem cell expression on
      disease outcomes was tested within multivariate analysis. RESULTS: One hundred
      fifty patients were included. The median dose to point A was 83 Gy (46-89 Gy) and
      a median of 4 cycles (range, 0-6 cycles) of chemotherapy was administered. At
      baseline, moderate to strong immunohistochemical expression of SOX-2, OCT-4,
      Nanog, CD44, and Podoplanin was observed in 12.8%, 4.8%, 24.4%, 15.5%, and 1.3%
      of patients, respectively. At median follow-up of 30 months (range, 3-51 months),
      locoregional and distant relapse was observed in 12.2% and 23.1% of patients, of
      whom 4.7% had both local and distant relapse. The 3-year disease-free survival
      rate was 87%. On multivariate analysis, moderate to high CSC expression and CD44
      low status (hazard ratio [HR] = 8.8; 95% confidence interval [CI], 1.0-77.2; P <
      .04) independently predicted for locoregional relapse-free survival.
      International Federation of Gynecology and Obstetrics stage (HR = 2.6; 95% CI,
      1.3-5.4; P = .004) and presence of residual tumor after external radiation (HR =
      3.5; 95% CI, 1.8-6.5; P = .0001) predicted for a detriment in disease-free
      survival. CONCLUSIONS: The presence of stem cell proteins and loss of CD44
      independently predicts for reduced locoregional control in locally advanced
      cervical cancer. Further investigation into the interaction of stem cell and CD44
      biology is warranted.

PMID- 30213751
TI  - MR Imaging Evaluation of Hepatocellular Carcinoma Treated with Stereotactic Body
      Radiation Therapy (SBRT): Long Term Imaging Follow-Up.
AB  - PURPOSE: To determine the natural history of imaging findings seen by MRI of
      hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy
      (SBRT). Although arterial hyperenhancement is a key feature of untreated HCC, our
      clinical experience suggested that tumors which never progressed could still show
      hyperenhancement. Therefore, we carried out a systematic study to test the
      hypothesis that persistent arterial phase hyperenhancement (APHE) following SBRT
      is an expected finding that does not suggest failure of treatment. METHODS: A
      total of 146 patients undergoing SBRT for HCC between 1/1/2007 and 12/31/2015
      were retrospectively screened using an IRB approved prospectively maintained
      registry. Inclusion criteria were: 1) HCC treated with SBRT, 2) multiphasic MRI
      <=3 months prior to SBRT, 3) up to 1 year of follow-up MRI post-SBRT, and 4)
      cirrhosis. Exclusion criterion was locoregional therapy <=3 months to the liver
      segment containing the SBRT-treated HCC. Pre- and post-SBRT MR imaging <=3 years
      was analyzed in consensus by independent pairs of subspecialty-trained
      radiologists to determine the temporal evolution of major features for HCC and
      imaging findings in off-target parenchyma. RESULTS: Sixty-two subjects with 67
      HCCs (Organ Procurement and Transplantation Network imaging criteria (OPTN) 5a
      [n=26], OPTN 5b [n=28], OPTN 5x [n=7], Liver Imaging Reporting Data System (LI
      RADs) LiRADs-M [n=4], LiRADs-4 [n=2]) were studied. Tumor size either decreased
      (66% [44/67]) or remained unchanged (34% [23/67]) within the first 12 months.
      Post-SBRT APHE was common (58% [39/67]). When graded by mRECIST criteria at 3-6
      months, 25% (17/67) met criteria for complete response (CR) and 75% (50/67) met
      criteria for stable disease (SD). CONCLUSION: SBRT is an effective locoregional
      treatment option for HCC. Persistent APHE is common and does not necessarily
      indicate viable neoplasm; thus, standard response assessment such as mRECIST
      should be used with caution, particularly in the early phases post-SBRT therapy.

PMID- 30213752
TI  - Preoperative Intensity-Modulated Radiotherapy Compared To Three-Dimensional
      Conformal Radiotherapy For High-Grade Extremity Sarcomas In Children: Analysis of
      the Childrens Oncology Group Study Arst0332.
AB  - BACKGROUND/OBJECTIVES: For pediatric patients with large, high-grade extremity
      non-rhabdomyosarcoma soft tissue sarcomas (NRSTS), preoperative radiation therapy
      (RT) provides the opportunity for smaller radiation fields and tumor shrinkage
      resulting in less extensive surgery. The potential disadvantage is an increased
      risk of wound complications after surgery compared to rates following
      postoperative chemoradiation. We assessed the impact of preoperative RT technique
      on target coverage in relationship to dose to skin and adjacent joints to
      determine if acute wound complications and late musculoskeletal injury might be
      influenced by treatment technique. DESIGN/METHODS: Of 550 eligible patients < 30
      years of age, 200 were enrolled in Arm D of ARST0332 and received neoadjuvant
      ifosfamide/doxorubicin, then chemoradiotherapy (45Gy and ifosfamide), and surgery
      followed by postoperative RT if gross or microscopic positive surgical margins.
      One-hundred thirteen patients had extremity NRSTS of which fifty-six patients had
      preoperative RT plans for digital review. The doses to the target volume, skin
      (surface to 5 mm depth), adjacent joint, and extremity diameter were analyzed
      with respect to RT technique. RESULTS: Thirty-eight patients (65%) received 3D
      conformal RT (3D-CRT) and 18 (32%) received intensity-modulated RT (IMRT). There
      was no difference in clinical target volume (CTV) size between groups (p=0.920);
      however, IMRT plans had improved CTV coverage to 100% of the prescription dose
      compared to 3D-CRT plans (median CTV coverage, 92.7% vs. 98.6%, p=0.011). In
      patients without target overlap with the skin, IMRT use was associated with
      reduced percent volume of skin receiving 45Gy or more (V45Gy) compared to 3D-CRT
      (median, 1.6% vs. 6.3% respectively, p=0.005). IMRT was also associated with
      reduced V45Gy to the adjacent joint compared to 3D-CRT (median, 1.1% vs. 13.2%,
      p=0.018). CONCLUSIONS: Preoperative IMRT may improve CTV coverage and reduce the
      volume of skin and adjacent joint treated to high doses. Future studies should
      assess if these dosimetric findings produce differences in clinical and toxicity
      outcomes.

PMID- 30213753
TI  - Assessment of time-resolved renal diffusion parameters over the entire cardiac
      cycle.
AB  - OBJECT: To assess changes diffusion properties of renal cortex over the entire
      cardiac cycle using electrocardiogram-gated respiratory-triggered dynamic
      diffusion-weighted imaging (DWI). MATERIALS AND METHODS: 20 healthy volunteers
      were investigated on a 1.5 T MR scanner. Blood flow velocity within the renal
      arteries was determined by electrocardiogram-gated phase-contrast measurements.
      For dynamic renal DWI, an electrocardiogram-gated respiratory-triggered coronal
      single-slice EPI sequence was acquired at 14 times at 20, 70, 120, 170, ..., 570,
      620, 720 ms after the R-wave over the cardiac cycle. ROI measurements were
      performed by two authors in the renal cortex on apparent diffusion coefficient
      (ADC) maps. A pulsatility index was calculated for ADC as maximal percentage
      change. Five subjects were measured twice to assess scan-rescan reproducibility.
      RESULTS: Flow measurements exhibited a minimum velocity of 15.7 +/- 4.3 cm/s
      during the R-wave and a maximum of 43.2 +/- 10.4 cm/s at 182.5 +/- 48.3 ms after
      the R-wave. A minimal mean ADC of 2.19 +/- 0.09 * 10-3 mm2/s was observed during
      the R-wave. A maximum mean ADC of 2.85 +/- 0.20 * 10-3 mm2/s was measured 193 +/-
      57 ms after the R-wave. The mean ADC pulsatility index in the renal cortex was
      29.9 +/- 5.8%. ADC variation exhibited a significant correlation with pulsatile
      blood flow velocity. The scan-rescan reproducibility in this study had a low
      deviation of 0.3 +/- 0.1%. The inter-reader reproducibility was 2.9 +/- 0.6%.
      CONCLUSION: Renal ADCs exhibit pulsatile characteristics. Due to the significant
      difference of systolic and diastolic ADCs, the pulsatility index can be
      calculated.

PMID- 30213754
TI  - Motion-compensated reconstruction of magnetic resonance images from undersampled
      data.
AB  - Magnetic resonance imaging of patients who find difficulty lying still or holding
      their breath can be challenging. Unresolved intra-frame motion yields blurring
      artifacts and limits spatial resolution. To correct for intra-frame non-rigid
      motion, such as in pediatric body imaging, this paper describes a multi-scale
      technique for joint estimation of the motion occurring during the acquisition and
      of the desired uncorrupted image. This technique regularizes the motion
      coefficients to enforce invertibility and minimize numerical instability. This
      multi-scale approach takes advantage of variable-density sampling patterns used
      in accelerated imaging to resolve large motion from a coarse scale. The resulting
      method improves image quality for a set of two-dimensional reconstructions from
      data simulated with independently generated deformations, with statistically
      significant increases in both peak signal to error ratio and structural
      similarity index. These improvements are consistent across varying undersampling
      factors and severities of motion and take advantage of the variable density
      sampling pattern.

PMID- 30213755
TI  - Anatomical accuracy of standard-practice tractography algorithms in the motor
      system - A histological validation in the squirrel monkey brain.
AB  - For two decades diffusion fiber tractography has been used to probe both the
      spatial extent of white matter pathways and the region to region connectivity of
      the brain. In both cases, anatomical accuracy of tractography is critical for
      sound scientific conclusions. Here we assess and validate the algorithms and
      tractography implementations that have been most widely used - often because of
      ease of use, algorithm simplicity, or availability offered in open source
      software. Comparing forty tractography results to a ground truth defined by
      histological tracers in the primary motor cortex on the same squirrel monkey
      brains, we assess tract fidelity on the scale of voxels as well as over larger
      spatial domains or regional connectivity. No algorithms are successful in all
      metrics, and, in fact, some implementations fail to reconstruct large portions of
      pathways or identify major points of connectivity. The accuracy is most dependent
      on reconstruction method and tracking algorithm, as well as the seed region and
      how this region is utilized. We also note a tremendous variability in the
      results, even though the same MR images act as inputs to all algorithms. In
      addition, anatomical accuracy is significantly decreased at increased distances
      from the seed. An analysis of the spatial errors in tractography reveals that
      many techniques have trouble properly leaving the gray matter, and many only
      reveal connectivity to adjacent regions of interest. These results show that the
      most commonly implemented algorithms have several shortcomings and limitations,
      and choices in implementations lead to very different results. This study should
      provide guidance for algorithm choices based on study requirements for
      sensitivity, specificity, or the need to identify particular connections, and
      should serve as a heuristic for future developments in tractography.

PMID- 30213756
TI  - Phytochemical and genetic characterization of styles of wild Crocus species from
      the island of Crete, Greece and comparison to those of cultivated C. sativus.
AB  - The aim of this study was to contribute to the characterization of Crocus taxa
      using morphological, phytochemical and genetic analysis. The styles of C.
      cartwrightianus, C. oreocreticus and C. laevigatus, collected in the island of
      Crete were compared to those of C. sativus cultivated at the region of Western
      Macedonia (Greece). Phytochemical analysis was done using GC-MS and HPLC methods,
      while ISSR markers were used for their genetic characterization. Safranal was the
      major volatile component of the styles of C. sativus, 4-hydroxy-2,6,6-trimethyl-1
      cyclohexene-1-carboxaldehyde of C. cartwrightianus and C. oreocreticus, and
      isophorone of C. laevigatus. C. sativus had the highest content of crocins and
      picrocrocin, while C. laevigatus the lowest (only 5% of C. sativus' quantity) and
      negligible amount of picrocrocin. According to both the genetic and the chemical
      analysis, C. cartwrightianus is more related to C. oreocreticus, while C. sativus
      and C. laevigatus are more distinct. Concordance between the two different types
      of data was also confirmed by the Mantel test (r = 0.932, P = .68). This is the
      first thorough screening of secondary metabolites (volatile and non-volatile) and
      also genetic and morphological characters of wild Crocus styles simultaneously,
      that contributes to the identification and valorisation of genotypes with similar
      to C. sativus traits which may be introduced as new cultivars through breeding.

PMID- 30213757
TI  - Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their
      cholinesterase inhibitory activities.
AB  - Four new trace alkaloids with lycodine-related structures, Lycocasuarinines A-D
      (1-4), together with seven known analogues (5-11), were isolated from the
      chloroform extract of Lycopodiastrum casuarinoides. The structures and
      stereochemistry of 1-4 were elucidated by spectroscopic analysis (IR, UV, MS,
      NMR, HRESIMS and CD) and comparison with known ones. The acetylcholinesterase
      (AChE) and butyrocholinesterase (BuChE) inhibitory activities of nine isolates
      were evaluated. Lycocasuarinine D (4) showed the most potent AChE inhibitory
      effect. In addition, a plausible biogenetic pathway of compound 4 was proposed.

PMID- 30213758
TI  - Antioxidant neolignans from the twigs and leaves of Mitrephora wangii HU.
AB  - Two new compounds, odoratisol E (1) and decurrenal A (2), together with 12 known
      compounds were isolated from the twig and leaf extracts of Mitrephora wangii HU
      (Annonaceae). All structures were elucidated by spectroscopic methods. The
      structure of compound (+)-6 was also confirmed by X-ray diffraction analysis. The
      absolute configurations of odoratisol E and decurrenal A were determined by
      comparison of their electronic circular dichroism (ECD) spectra with those of
      related known compounds. Most of the isolated compounds were evaluated for their
      antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'
      azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Compounds 4 and
      (+)-6 displayed potent ABTS radical scavenging activity with IC50 values of 11.9
      +/- 1.8 and 10.8 +/- 1.7 MUM, respectively, which is better than that of standard
      compound, ascorbic acid, (IC50 = 19.3 +/- 0.1 MUM). Compound 9 showed moderate
      DPPH radical scavenging activity with an IC50 value of 38.7 +/- 0.8 MUM.

PMID- 30213759
TI  - Localization of phenolic compounds in the fruits of Silybum marianum
      characterized by different silymarin chemotype and altered colour.
AB  - Silybum marianum (L.) Gaertn (Asteraceae) is a valuable medicinal plant utilized
      for silymarin production. However, only fragmentary and contradictory information
      about silymarin localization within S. marianum fruit are available. In this
      work, a twofold research approach was adopted in order to investigate the
      distribution and quantification of silymarin and of other phenolic compounds
      within the different fruit regions (pericarp, seed integument, cotyledon). Two S.
      marianum wild accessions with contrasting silymarin chemotype (A and B) and a
      mutant line (C) with an altered fruit colour were analysed. Fruits of Cynara
      cardunculus were studied as a reference. Firstly, the fruit morpho-anatomy was
      reviewed by means of light microscopy digital imaging and, secondly, a
      comprehensive histolocalization of the different classes of polyphenols within
      the fruit was carried out. The experimental evidences confirmed that silymarin,
      and its precursor taxifolin, are only accumulated in the seed integuments. The
      dark colour of fully-ripened fruits is due to the accumulation of condensed
      tannins in the pericarp subepidermal cell layer. On the contrary, the studied
      mutant line shows reduced condensed tannin content that probably result from
      impairment at the level of flavonoid biosynthetic pathway. Condensed tannins
      content is comparatively low in S. marianum fruits and very low in the identified
      mutant line. This could represent an advantage for the possible employment of S.
      marianum fruits and of silymarin extraction by-products in the feed and food
      sector.

PMID- 30213760
TI  - The role of ubiquitination in the regulation of primary cilia assembly and
      disassembly.
AB  - The primary cilium is a cellular antenna found on the surface of many eukaryotic
      cells, whose main role is to sense and transduce signals that regulate growth,
      development, and differentiation. Although once believed to be a vestigial
      organelle without important function, it has become clear that defects in primary
      cilium are responsible for a wide variety of genetic diseases affecting many
      organs and tissues, including the brain, eyes, heart, kidneys, liver, and
      pancreas. The primary cilium is mainly present in quiescent and differentiated
      cells, and controls must exist to ensure that this organelle is assembled or
      disassembled at the right time. Although many protein components required for
      building the cilium have been identified, mechanistic details of how these
      proteins are spatially and temporally regulated and how these regulations are
      connected to external cues are beginning to emerge. This review article
      highlights the role of ubiquitination and in particular, E3 ubiquitin ligases and
      deubiquitinases, in the control of primary cilia assembly and disassembly.

PMID- 30213761
TI  - Systemic lupus erythematosus: A new autoimmune disorder in Kabuki syndrome.
AB  - We report a case of a 17-year-old Caucasian girl with syndromic features of
      clinically unrecognized Kabuki syndrome (KS), who developed systemic lupus
      erythematosus (SLE). Diagnosis of KS was established after whole exome sequencing
      (WES) and detection of de novo frameshift 1bp deletion in histone-lysine N
      methyltransferase 2D gene (KMT2D). The pathogenic variant in exon 34 (c.8626delC:
      55 reads C, 56 reads delC), has not been described previously and is predicted to
      truncate the protein (p.Gln2876Serfs*34) resulting in KMT2D loss of function.
      Notwithstanding that patients with KS have a substantial susceptibility to
      various autoimmune diseases, to the best of our knowledge this is the first
      report of an SLE and KS association. The exact relationship between the two
      conditions in our patient is difficult to determine with certainty, as a number
      of clinical features, including positive antiphospholipid antibodies, persistent
      hypogammaglobulinemia and the episode of convulsions may occur in both
      conditions, suggesting potential overlap of KS and SLE. The combination of a high
      susceptibility towards infections and an autoimmune disorder present a great
      challenge when trying to achieve the optimum therapy which will enable the
      patient to stay on the thin line of remission. This case report emphasizes the
      value of WES as a powerful tool for the diagnosis of rare disorders and/or
      unusual disease presentations of possible genetic cause.

PMID- 30213762
TI  - Further evidence of a causal association between AGO1, a critical regulator of
      microRNA formation, and intellectual disability/autism spectrum disorder.
AB  - Among the many regulators of microRNA formation, Argonaute 1 (AGO1) plays
      critical roles in RNA interference, which controls a wide range of biological
      activities. Recent large-scale genomic studies have identified at least five
      patients with intellectual disability/autism spectrum disorder who had de novo
      mutations in AGO1, but detailed clinical information was not available. The
      recognizable clinical features that are associated with AGO1 mutations remain to
      be determined. The proposita was a 15-year-old girl with diffuse hypotonia,
      infrequent seizures, and intellectual disability with an intelligence quotient of
      41. She had characteristic facial features consisting of telecanthus, wide nasal
      bridge with bulbous nasal tip, and a round face with downslanted palpebral
      fissures. Serial computed tomography scans showed progressive calcification in
      the globus pallidus that became evident during childhood. A whole exome analysis
      in trio revealed a de novo heterozygous mutation in AGO1, i.e., c.595G > A
      p.(Gly199Ser). The distinctive facial features, i.e., telecanthus, wide nasal
      bridge with bulbous nasal tip, and a round face with downslanted palpebral
      fissures, closely resembled previously reported patients who had a chromosomal
      microdeletion encompassing AGO1 locus. The combinatory phenotype of such
      characteristic facial features and radiographic features, i.e. progressive
      calcification in the globus pallidus, in the presently reported patient suggest
      that AGO1 mutations lead to a syndromic form of intellectual disability/autism
      spectrum disorder. Distinctive facial features with early and progressive
      calcification in the globus pallidus may be suggestive of the presence of AGO1
      mutations.

PMID- 30213763
TI  - Is antibiotic prophylaxis mandatory in laparoscopic incisional hernia repair?
      Data from the herniamed registry.
AB  - BACKGROUND: Several meta-analyses showed that laparoscopic incisional hernia
      repair is associated with lower surgical site infection (SSI) rates compared to
      open repair. However, the efficiency of antibiotic prophylaxis (AP) in
      laparoscopic incisional hernia repair alone is unknown and needs evaluation. Due
      to increasing antimicrobial resistance, a major global health care problem, AP
      needs to be critically evaluated. The aim of this study was to investigate the
      impact of AP on the rate of SSI and complication-related reoperations in patients
      undergoing laparoscopic incisional hernia repair. MATERIALS AND METHODS:
      Prospectively documented data from the Herniamed Hernia Registry from 2009 to
      2017 were retrospectively analysed. Multivariable analyses were used to study the
      influence of AP as well as further patient and surgery-related risk factors on
      SSI and complication-related reoperation rates. This was verified in a
      sensitivity analysis using propensity-score matching. RESULTS: In the analysed
      time period 13'513 patients undergoing elective laparoscopic incisional hernia
      repair were recorded, of which 14.4% (n = 1949) did not receive AP. The overall
      SSI rate showed no significant difference when directly comparing patients with
      (0.74%) and without AP (0.97%; p = 0.262). In the multivariable analysis the
      presence of patient related risk factors (p = 0.015) and defect size >10 cm (p =
      0.035) significantly increased the rates of SSI and complication-related
      reoperations. The propensity-score matching analysis verified that SSI rates are
      not significantly different between the two groups (p = 0.265). CONCLUSIONS: In
      cases of laparoscopic incisional hernia repair in patients without risk factors
      and moderate hernia diameter (<10 cm), routine administration of AP in
      laparoscopic incisional hernia repair does not seem to be justified.

PMID- 30213764
TI  - Impact of hydrodynamics on iPSC-derived cardiomyocyte differentiation processes.
AB  - Cardiomyocytes (CMs), derived from pluripotent stem cells (PSCs), have the
      potential to be used in cardiac repair. Addition of physical cues, such as
      electrical and mechanical stimulations, have proven to significantly effect
      morphology, density, cardiogenesis, maturity and functionality of differentiated
      CMs. This work combines rigorous fluid dynamics investigation and flow frequency
      analysis with iPSC differentiation experiments to identify and quantify the flow
      characteristics leading to a significant increase of differentiation yield. This
      is towards a better understanding of the physical relationship between frequency
      modulation and embryoid bodies suspension, and the development of dimensionless
      correlations applicable at larger scales. Laser Doppler Anemometry and Fast
      Fourier Transform analysis were used to identify characteristic flow frequencies
      under different agitation modes. Intermittent agitation resulted in a pattern of
      low intensity frequencies at reactor scale that could be controlled by varying
      three identified time components: rotational speed, interval and dwell times. A
      proof of concept biological study was undertaken, tuning the hydrodynamic
      environment through variation of dwell time based on the engineering study
      findings and a significant improvement in CM yield was obtained. This work
      introduces the concept of fine-tuning the physical hydrodynamic cues within a
      three-dimensional flow system to improve cardiomyocyte differentiation of iPSC.

PMID- 30213765
TI  - Src is Implicated in Hepatic Ischemia Reperfusion-Induced Hippocampus Injury and
      Long-Term Cognitive Impairment in Young Mice via NMDA Receptor Subunit 2A
      Activation.
AB  - Hepatic ischemia reperfusion (HIR) has been found to induce hippocampus injury
      and cognitive dysfunction. The N-methyl-d-aspartate (NMDA) receptor subunit 2A
      (NR2A) is an important factor mediating excitotoxicity and neurons injury, and
      autophosphorylation of Src can up-regulate tyrosine phosphorylation of NR2A to
      improve its activity. However, the role of Src and NR2A in HIR-induced
      hippocampus injury in young mice remains unknown. In this study, we found that
      serum biomarkers of brain injury (S100beta and NSE) increased significantly and
      reached highest after reperfusion of 3 days which had the same trend with the
      levels of p-Src and p-NR2A. Interactions between Src and NR2A or PSD95 were
      increased after HIR. Hippocampal neuron apoptosis was increased, and long-term
      cognitive impairment was found after reperfusion of 1 month. Inhibition of Src
      and NR2A with PP2 and NVP-AAM077 respectively not only down-regulated the levels
      of p-Src and p-NR2A, but also ameliorated hippocampal neurons apoptosis and long
      term cognitive impairment after HIR. Serum alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-alpha),
      interferon-gamma (IFN-gamma) and interleukin (IL)-6 were increased after
      reperfusion of 3 days, while PP2 and NVP-AAM077 treatment didn't attenuate the
      changes. And no difference was found in serum TNF-alpha, IFN-gamma, IL-6
      concentrations as well as the levels of Src, p-Src, NR2A, p-NR2A, PSD95 among the
      four groups after reperfusion of 1 month. In summary, HIR can lead to hippocampus
      injury and long-term cognitive dysfunction, and Src-PSD95-NR2A pathway plays an
      important role in the process.

PMID- 30213767
TI  - Neural Mechanisms of Material Perception: Quest on Shitsukan.
AB  - In recent years, a growing body of research has addressed the nature and
      mechanism of material perception. Material perception entails perceiving and
      recognizing a material, surface quality or internal state of an object based on
      sensory stimuli such as visual, tactile, and/or auditory sensations. This process
      is ongoing in every aspect of daily life. We can, for example, easily distinguish
      whether an object is made of wood or metal, or whether a surface is rough or
      smooth. Judging whether the ground is wet or dry or whether a fish is fresh also
      involves material perception. Information obtained through material perception
      can be used to govern actions toward objects and to make decisions about whether
      to approach an object or avoid it. Because the physical processes leading to
      sensory signals related to material perception is complicated, it has been
      difficult to manipulate experimental stimuli in a rigorous manner. However, that
      situation is now changing thanks to advances in technology and knowledge in
      related fields. In this article, we will review what is currently known about the
      neural mechanisms responsible for material perception. We will show that cortical
      areas in the ventral visual pathway are strongly involved in material perception.
      Our main focus is on vision, but every sensory modality is involved in material
      perception. Information obtained through different sensory modalities is closely
      linked in material perception. Such cross-modal processing is another important
      feature of material perception, and will also be covered in this review.

PMID- 30213768
TI  - Assessing the quality of single particle reconstructions by atomic model
      building.
AB  - The 2015/2016 Map Challenge challenged cryo-EM practitioners to process a series
      of publicly available cryo-EM datasets. As part of the challenge, metrics needed
      to be developed to assess and compare the quality of the different map
      submissions. The most common metric for assessing maps is determining the
      resolution by Fourier shell correlation (FSC), but there are well known instances
      where the resolution can be misleading. In this manuscript, we present a new
      approach for assessing the quality of a map by determining the map "modelability"
      rather than on resolution. We used the automated map tracing and modeling
      algorithms in Rosetta to generate populations of models, and then compared the
      populations between different map entries by the Rosetta score, RMSD to a
      reference model provided by the map challenge, and by pair-wise RMSDs between
      different models in the population. These metrics were used to determine
      statistically significant rankings for the map challengers for each dataset. The
      rankings revealed inconsistencies between the resolution by FSC, emphasized the
      importance of the interplay between number of particles contributing to a map and
      map quality, and revealed the importance of software familiarity on single
      particle reconstruction results. However, because multiple variables changed
      between map entries, it was challenging to derive best practices from the map
      challenge results.

PMID- 30213769
TI  - Modular ceramic scaffolds for individual implants.
AB  - Ideal artificial bone grafts aim for multiscale porosity, high mechanical
      strength and ensure rapid vascularization for bone ingrowth. In this work modular
      ceramic arteriovenous loops (AV-loops) with a hierarchical porosity approach were
      designed and manufactured to meet these criteria and to exceed the poor
      mechanical strength of monolithic scaffolds. Bioactive building blocks (beta-TCP,
      HAp, BCP) with dimensions of 1.5-3.0 mm were prepared by injection molding and
      assembled to complex AV-loop scaffolds using a customized automated assembly
      technology (pick and place). The building blocks were bonded with a biocompatible
      adhesive. Single building blocks are characterized by a compressive strength of
      112.4-134.5 MPa with a residual sintering porosity of 32.2-41.5%, matching the
      strength of cortical bone of 100-230 MPa. The compressive strength of the modular
      assemblies varied between 22.3 and 47.6 MPa primary depending on the building
      block arrangement. The achieved compressive strengths are superior to current
      monolithic AV-scaffolds and sufficient for the implantation as non-load-bearing
      AV-loop scaffolds in isolation chambers. The modular AV-loop scaffolds provide a
      hierarchical interconnected pore network (P = 58.8%) combining small macropores
      of 4.1-4.3 um size for possible enhanced protein absorption and large gradient
      macropores of 200-1700 um size for optimum vascularization and complete bone
      ingrowth. The modular building block approach allows to design patient
      individualized scaffolds with complex hierarchical pore networks. The pore
      volume, size and geometry as well as the biological response can effectively be
      tuned by changing the dimensions, shape and placing gap of the bioactive building
      blocks. STATEMENT OF SIGNIFICANCE: Gold standard of bone replacement in case of
      surgery or cancer is still own bone material usually taken from the hip/arm or
      leg in second surgery with poor mechanical properties and limited amount. To
      avoid a second surgery and provide mechanical strong scaffold structures for fast
      patient regeneration a novel modular building block approach is used. This allows
      complex scaffold geometry with a hierarchical interconnection porosity for blood
      vessel ingrowth. The pore volume, size and geometry as well as the biological
      response can effectively be tuned by changing the dimensions, shape and placing
      gap of the bioactive building blocks.

PMID- 30213770
TI  - In utero exposure to gestational diabetes mellitus and long term endocrine
      morbidity of the offspring.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is a worldwide public health
      problem. Few studies investigated the association of intra uterine exposure to
      GDM and long-term endocrine morbidity of offspring. OBJECTIVE: To assess whether
      in utero exposure to GDM increases the risk for long-term endocrine morbidity of
      the offspring. METHODS: A retrospective cohort study was conducted including all
      singleton born to women who delivered between 1988 and 2014. All births occurred
      in a tertiary medical center. Data were collected from the computerized perinatal
      database of the obstetrics and gynecology department and the computerized
      hospitalization database. The exposure variables were: diet-controlled GDM
      (GDMA1) and treated GDM (GDMA2). Multivariate generalized estimating equation
      (GEE) logistic regression model analysis was used to control for confounders and
      for maternal clusters. RESULTS: During the study period 231,271 deliveries met
      the inclusion criteria, of which 12,642 deliveries (5.4%) were diagnosed with
      GDM. During the follow-up period, children exposed in utero to GDM had a higher
      rate of long- term hospitalizations with diagnoses of endocrine morbidity (such
      as diabetes mellitus and obesity) compared to those unexposed. Using a GEE model,
      controlling for confounders such as maternal age, follow up-time, obesity and
      birthweight, in-utero exposure to GDMA1 (adjusted OR = 2.1; 95% CI 1.7-2.7; P <
      0.001) and especially to GDMA2 (adjusted OR = 3.1; 95% CI 2.2-4.4, P < 0.001)
      were found as risk factors for long-term endocrine disease during childhood.
      CONCLUSION: Exposure to GDM is a risk factor for long-term endocrine morbidity in
      the offspring.

PMID- 30213766
TI  - Kainate Receptors Play a Role in Modulating Synaptic Transmission in the
      Olfactory Bulb.
AB  - Glutamate is the neurotransmitter used at most excitatory synapses in the
      mammalian brain, including those in the olfactory bulb (OB). There, ionotropic
      glutamate receptors including N-methyl-d-aspartate receptors (NMDARs) and alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) play a role
      in processes such as reciprocal inhibition and glomerular synchronization.
      Kainate receptors (KARs) represent another type of ionotropic glutamate receptor,
      which are composed of five (GluK1-GluK5) subunits. Whereas KARs appear to be
      heterogeneously expressed in the OB, evidence as to whether these KARs are
      functional, found at synapses, or modify synaptic transmission is limited. In the
      present study, coapplication of KAR agonists (kainate, SYM 2081) and AMPAR
      antagonists (GYKI 52466, SYM 2206) demonstrated that functional KARs are
      expressed by OB neurons, with a subset of receptors located at synapses.
      Application of kainate and the GluK1-selective agonist ATPA had modulatory
      effects on excitatory postsynaptic currents (EPSCs) evoked by stimulation of the
      olfactory nerve layer. Application of kainate and ATPA also had modulatory
      effects on reciprocal inhibitory postsynaptic currents (IPSCs) evoked using a
      protocol that evokes dendrodendritic inhibition. The latter finding suggests that
      KARs, with relatively slow kinetics, may play a role in circuits in which the
      relatively brief duration of AMPAR-mediated currents limits the role of AMPARs in
      synaptic transmission (e.g., reciprocal inhibition at dendrodendritic synapses).
      Collectively, our findings suggest that KARs, including those containing the
      GluK1 subunit, modulate excitatory and inhibitory transmission in the OB. These
      data further suggest that KARs participate in the regulation of synaptic circuits
      that encode odor information.

PMID- 30213771
TI  - Incidence of diabetic eye disease among migrants: A cohort study of 100,000
      adults with diabetes in Denmark.
AB  - AIMS: To examine the incidence rates of any and referable diabetic retinopathy
      (DR) among migrants in Denmark. METHODS: Nationwide clinical data on diabetes
      patients followed since 2005 were analysed. Patients were classified according to
      country of origin into six groups: Denmark, other Europe, Sub Saharan Africa,
      Middle East/North Africa, Asia, and America/Oceania. A total of 93,780 or 110,897
      patients without any (including unspecific diagnoses) or referable
      (proliferative) DR at baseline were analyzed. We estimated event rates and hazard
      ratios (HRs) for incidence of any and referable DR according to country of
      origin. RESULTS: After an average follow-up of 3.59 years 6727 had incident any
      DR and 4747 patients had referable DR. Compared to people of Danish origin,
      migrants from the Middle East/North Africa and Asia had a higher risk of any and
      referable DR after adjustment for age, sex, body mass index, smoking status,
      types and duration of diabetes, clinic type (general practice vs outpatient
      clinic), HbA1c, blood pressure and lipid levels. The associations remained
      significant after further adjustment for frequency of eye screening. CONCLUSIONS:
      Migrants from the Middle East/North Africa and Asia were at increased risk of
      developing any and referable DR compared to native Danes, and these differences
      were not fully explained by differences in underlying clinical, diabetic and
      cardiometabolic risk factors.

PMID- 30213772
TI  - Glucagon secretion determined by the RIA method is lower in patients with low
      left ventricular ejection fraction: The new glass study.
AB  - AIMS: We investigated the glucagon levels in patients with heart failure (HF),
      using long oral glucose tolerance test (OGTT). METHODS: In this prospective
      observational study, we enrolled 30 undiagnosed diabetes patients (age 69 +/- 10
      years, 70% males, HbA1c 43 mmol/mol). A 4-h OGTT was performed. Glucose, insulin,
      and glucagon (radioimmunoassay [RIA] and sandwich ELISA [S-W] methods) were
      evaluated during 4-h. We compared glucagon levels between HF and non-HF patients.
      RESULTS: There were 11 HF and 19 non-HF patients. In patients with HF, glucagon
      (S-W) during 4-h was lower than in patients without HF, with no significant
      difference. The area under the curve (AUC) of glucagon (RIA) during 4-h was
      significantly lower among HF patients. Moreover, in patients with reduced left
      ventricular ejection fraction (LVEF) (<40%), AUC glucagon (RIA) was significantly
      lower than in patients with non-reduced EF (>=40%). However, there was no
      difference in glucagon values between the high E/e' (>=13.0) and low E/e' (<13.0)
      groups. CONCLUSIONS: Although glucagon (S-W) showed no significant difference in
      patients with and without HF, especially reduced LVEF, glucagon (RIA) secretion
      was significantly lower in HF patients than in patients without HF. It is
      suggested that low glucagon secretion might be correlated with low EF.

PMID- 30213773
TI  - Fasting in Ramadan of Muslim patients with diabetes Mellitus, and knowledge and
      practice in relation to diabetes control in Brunei.
AB  - AIM: To investigate the fasting pattern of patients with Diabetes Mellitus in
      Brunei Darussalam, specifically, their fasting activities, and knowledge and
      practice in relation to diabetes control during fasting in Ramadan. METHODS:
      Cross-sectional study that included 18 years and older, Muslim patients with
      diabetes Mellitus who attended the main Diabetes Centre in Brunei. A self
      administered questionnaire was designed, tested and used to collect the
      demographic information, fasting duration, knowledge and practice on diabetes
      control during fasting, and reasons of fasting as a Muslim. RESULTS: 183
      participants with a mean age of 53.7 (SD 11.52) years were recruited. Prevalence
      of fasting during Ramadan was 93.4% with an average number of days of fasting was
      24.1 days. Those with age 55 and above had significant higher prevalence of
      fasting than the younger group (p = 0.010). Only 49.1% of participants had
      consulted their healthcare professionals of their intentions to fast prior to the
      Ramadan, and only 38.1% of participants monitored blood glucose levels throughout
      the month. CONCLUSIONS: Diabetes education and early treatment adjustment
      especially before and during the month of Ramadan is essential to minimize
      hypoglycaemic risks and frequency of diabetes complications.

PMID- 30213774
TI  - Somatosensory responses to nothing: An MEG study of expectations during omission
      of tactile stimulations.
AB  - The brain builds up expectations to future events based on the patterns of past
      events. This function has been studied extensively in the auditory and visual
      domains using various oddball paradigms, but only little exploration of this
      phenomenon has been done in the somatosensory domain. In this study, we explore
      how expectations of somatosensory stimulations are established and expressed in
      neural activity as measured with magnetoencephalography. Using tactile
      stimulations to the index finger, we compared conditions with actual stimulation
      to conditions with omitted stimulations, both of which were either expected or
      unexpected. Our results show that when a stimulation is expected but omitted, a
      time-locked response occurs ~135 ms subsequent to the expected stimulation. This
      somatosensory response to "nothing" was source localized to the secondary
      somatosensory cortex and to the insula. This provides novel evidence of the
      capability of the brain of millisecond time-keeping of somatosensory patterns
      across intervals of 3000 ms. Our results also show that when stimuli are repeated
      and expectations are established, there is associated activity in the theta and
      beta bands. These theta and beta band expressions of expectation were localized
      to the primary somatosensory area, inferior parietal cortex and cerebellum.
      Furthermore, there was gamma band activity in the right insula for the first
      stimulation after an omission, which indicates the detection of a new stimulation
      event after an expected pattern has been broken. Finally, our results show that
      cerebellum play a crucial role in predicting upcoming stimulation and in
      predicting when stimulation may begin again.

PMID- 30213775
TI  - Load modulates the alpha and beta oscillatory dynamics serving verbal working
      memory.
AB  - A network of predominantly left-lateralized brain regions has been linked to
      verbal working memory (VWM) performance. However, the impact of memory load on
      the oscillatory dynamics serving VWM is far less understood. To further
      investigate this, we had 26 healthy adults perform a high-load (6 letter) and low
      load (4 letter) variant of a VWM task while undergoing magnetoencephalography
      (MEG). MEG data were evaluated in the time-frequency domain and significant
      oscillatory responses spanning the encoding and maintenance phases were
      reconstructed using a beamformer. To determine the impact of load on the neural
      dynamics, the resulting images were examined using paired-samples t-tests and
      virtual sensor analyses. Our results indicated stronger increases in frontal
      theta activity in the high- relative to low-load condition during early encoding.
      Stronger decreases in alpha/beta activity were also observed during encoding in
      bilateral posterior cortices during the high-load condition, and the strength of
      these load effects increased as encoding progressed. During maintenance, stronger
      decreases in alpha activity in the left inferior frontal gyrus, middle temporal
      gyrus, supramarginal gyrus, and inferior parietal cortices were detected during
      high- relative to low-load performance, with the strength of these load effects
      remaining largely static throughout maintenance. Finally, stronger increases in
      occipital alpha activity were observed during maintenance in the high-load
      condition, and the strength of these effects grew stronger with time during the
      first half of maintenance, before dissipating during the latter half of
      maintenance. Notably, this was the first study to utilize a whole-brain approach
      to statistically evaluate the temporal dynamics of load-related oscillatory
      differences during encoding and maintenance processes, and our results highlight
      the importance of spatial, temporal, and spectral specificity in this regard.

PMID- 30213777
TI  - Investigating the Relationship Between Eye Movement and Brain Wave Activity Using
      Video Games: Pilot Study.
AB  - BACKGROUND: All eye movements are related in one way or another to our mental
      processes with lateral eye movements being associated with the different
      hemispheres of the brain. Eye movement techniques form the basis of eye movement
      desensitization and reprocessing therapy, wherein forced eye movements activate
      neurological pathways to treat the subject. OBJECTIVE: The objective of our study
      was to examine the relationship between players' eye movements and their brain
      wave activities using a video game. METHODS: We used similar eye movement
      techniques in the form of a video game called Lifeguard that could potentially
      stimulate different eye movement mode and create a more engaging experience for
      the user. By designing an experiment, we further explored the differences in
      electroencephalogram spectral power activity for the alpha, beta, theta, delta,
      and gamma frequency bands in Lifeguard and Tetris. RESULTS: The game based on eye
      movement technologies resulted in decreased delta power and increased beta power,
      but significant difference between 2 games was not found. CONCLUSIONS: The
      applied uses of this research could mean that eye movement desensitization and
      reprocessing can be conducted in a more fun and engaging way through the use of
      gaming technology.

PMID- 30213776
TI  - Irritability uniquely predicts prefrontal cortex activation during preschool
      inhibitory control among all temperament domains: A LASSO approach.
AB  - Temperament, defined as individual variation in the reactivity and regulation of
      emotional, motor, and attentional processes, has been shown to influence
      emotional and cognitive development during the preschool period (ages 4-5). While
      relationships between temperament and neural activity have been investigated
      previously, these have typically investigated individual temperament dimensions
      selected ad hoc. Since significant correlations exist between various temperament
      dimensions, it remains unclear whether these findings would replicate while
      analyzing all temperament dimensions simultaneously. Using functional near
      infrared spectroscopy (fNIRS), 4-5-year-old children (N = 118) were administered
      a Go/No-Go task to assess prefrontal cortex activation during inhibitory control.
      The relationship between PFC activation and all 15 temperament domains defined by
      the Children's Behavior Questionnaire (CBQ) was assessed using automatic feature
      selection via LASSO regression. Results indicate that only the Anger/Frustration
      dimension was predictive of activation during the inhibitory control task. These
      findings support previous work showing relationships between irritability and
      prefrontal activation during executive function and extend those findings by
      demonstrating the specificity of the activation-irritability relationship among
      temperament dimensions.

PMID- 30213778
TI  - Automatic Extraction of Mental Health Disorders From Domestic Violence Police
      Narratives: Text Mining Study.
AB  - BACKGROUND: Vast numbers of domestic violence (DV) incidents are attended by the
      New South Wales Police Force each year in New South Wales and recorded as both
      structured quantitative data and unstructured free text in the WebCOPS (Web-based
      interface for the Computerised Operational Policing System) database regarding
      the details of the incident, the victim, and person of interest (POI). Although
      the structured data are used for reporting purposes, the free text remains
      untapped for DV reporting and surveillance purposes. OBJECTIVE: In this paper, we
      explore whether text mining can automatically identify mental health disorders
      from this unstructured text. METHODS: We used a training set of 200 DV recorded
      events to design a knowledge-driven approach based on lexical patterns in text
      suggesting mental health disorders for POIs and victims. RESULTS: The precision
      returned from an evaluation set of 100 DV events was 97.5% and 87.1% for mental
      health disorders related to POIs and victims, respectively. After applying our
      approach to a large-scale corpus of almost a half million DV events, we
      identified 77,995 events (15.83%) that mentioned mental health disorders, with
      76.96% (60,032/77,995) of those linked to POIs versus 16.47% (12,852/77,995) for
      the victims and 6.55% (5111/77,995) for both. Depression was the most common
      mental health disorder mentioned in both victims (22.30%, 3258) and POIs (18.73%,
      8918), followed by alcohol abuse for POIs (12.24%, 5829) and various anxiety
      disorders (eg, panic disorder, generalized anxiety disorder) for victims (11.43%,
      1671). CONCLUSIONS: The results suggest that text mining can automatically
      extract targeted information from police-recorded DV events to support further
      public health research into the nexus between mental health disorders and DV.

PMID- 30213779
TI  - Using a ResearchKit Smartphone App to Collect Rheumatoid Arthritis Symptoms From
      Real-World Participants: Feasibility Study.
AB  - BACKGROUND: Using smartphones to enroll, obtain consent, and gather self-reported
      data from patients has the potential to enhance our understanding of disease
      burden and quantify physiological impact in the real world. It may also be
      possible to harness integral smartphone sensors to facilitate remote collection
      of clinically relevant data. OBJECTIVE: We conducted the Patient Rheumatoid
      Arthritis Data From the Real World (PARADE) observational study using a
      customized ResearchKit app with a bring-your-own-device approach. Our objective
      was to assess the feasibility of using an entirely digital approach (social media
      and smartphone app) to conduct a real-world observational study of patients with
      rheumatoid arthritis. METHODS: We conducted this observational study using a
      customized ResearchKit app with a bring-your-own-device approach. To recruit
      patients, the PARADE app, designed to guide patients through a series of tasks,
      was publicized via social media platforms and made available for patients in the
      United States to download from the Apple App Store. We collected patient-reported
      data, such as medical history, rheumatoid arthritis-related medications (past and
      present), and a range of patient-reported outcome measures. We included in the
      assessment a joint-pain map and a novel objective assessment of wrist range of
      movement, measured by the smartphone-embedded gyroscope and accelerometer.
      RESULTS: Within 1 month of recruitment via social media campaigns, 399
      participants self-enrolled, self-consented, and provided complete demographic
      data. Joint pain was the most frequently reported rheumatoid arthritis symptom to
      bother study participants (344/393, 87.5%). Severe patient-reported wrist pain
      appeared to be inversely linked with the range of wrist movement measured
      objectively by the app. At study entry, 292 of 399 participants (73.2%) indicated
      a preference for participating in a mobile app-based study. The number of
      participants in the study declined to 45 of 399 (11.3%) at week 12. CONCLUSIONS:
      Despite the declining number of participants over time, the combination of social
      media and smartphone app with sensor integration was a feasible and cost
      effective approach for the collection of patient-reported data in rheumatoid
      arthritis. Integral sensors within smartphones can be harnessed to provide novel
      end points, and the novel wrist range of movement test warrants further clinical
      validation.

PMID- 30213780
TI  - Blockchain Technology for Detecting Falsified and Substandard Drugs in
      Distribution: Pharmaceutical Supply Chain Intervention.
AB  - BACKGROUND: Drug counterfeiting is a global problem with significant risks to
      consumers and the general public. In the Philippines, 30% of inspected drug
      stores in 2003 were found with substandard/spurious/falsely
      labeled/falsified/counterfeit drugs. The economic burden on the population drug
      expenditures and on governments is high. The Philippine Food and Drug
      Administration (FDA) encourages the public to check the certificates of product
      registration and report any instances of counterfeiting. The National Police of
      Philippines responds to such reports through a special task force. However, no
      literature on its impact on the distribution of such drugs were found. Blockchain
      technology is a cryptographic ledger that is allegedly immutable through repeated
      sequential hashing and fault-tolerant through a consensus algorithm. This project
      will develop and test a pharmacosurveillance blockchain system that will support
      information sharing along the official drug distribution network. OBJECTIVE: This
      study aims to develop a pharmacosurveillance blockchain system and test its
      functions in a simulated network. METHODS: We are developing a Distributed
      Application (DApp) that will run on smart contracts, employing Swarm as the
      Distributed File System (DFS). Two instances will be developed: one for Ethereum
      and another for Hyperledger Fabric. The proof-of-work (PoW) consensus algorithm
      of Ethereum will be modified into a delegated proof-of-stake (DPoS) or practical
      Byzantine fault tolerance (PBFT) consensus algorithm as it is scalable and fits
      the drug supply chain environment. The system will adopt the GS1 pedigree
      standard and will satisfy the data points in the data standardization guidelines
      from the US FDA. Simulations will use the following 5 nodes: for FDA,
      manufacturer, wholesaler, retailer, and the consumer portal. RESULTS: Development
      is underway. The design of the system will place FDA in a supervisory data
      verification role, with each pedigree type-specific data source serving a primary
      data verification role. The supply chain process will be initiated by the
      manufacturer, with recursive verification for every transaction. It will allow
      consumers to scan a code printed on the receipt of their purchases to review the
      drug distribution history. CONCLUSIONS: Development and testing will be conducted
      in a simulated network, and thus, results may differ from actual practice. The
      project being proposed is disruptive; once tested, the team intends to engage the
      Philippine FDA to discuss implementation plans and formulate policies to
      facilitate adoption and sustainability. REGISTERED REPORT IDENTIFIER: RR1
      10.2196/10163.

PMID- 30213781
TI  - Reach of Messages in a Dental Twitter Network: Cohort Study Examining User
      Popularity, Communication Pattern, and Network Structure.
AB  - BACKGROUND: Increasing the reach of messages disseminated through Twitter
      promotes the success of Twitter-based health education campaigns. OBJECTIVE: This
      study aimed to identify factors associated with reach in a dental Twitter network
      (1) initially and (2) sustainably at individual and network levels. METHODS: We
      used instructors' and students' Twitter usernames from a Saudi dental school in
      2016-2017 and applied Gephi (a social network analysis tool) and social media
      analytics to calculate user and network metrics. Content analysis was performed
      to identify users disseminating oral health information. The study outcomes were
      reach at baseline and sustainably over 1.5 years. The explanatory variables were
      indicators of popularity (number of followers, likes, tweets retweeted by
      others), communication pattern (number of tweets, retweets, replies, tweeting/
      retweeting oral health information or not). Multiple logistic regression models
      were used to investigate associations. RESULTS: Among dental users, 31.8% had
      reach at baseline and 62.9% at the end of the study, reaching a total of 749,923
      and dropping to 37,169 users at the end. At an individual level, reach was
      associated with the number of followers (baseline: odds ratio, OR=1.003, 95%
      CI=1.001-1.005 and sustainability: OR=1.002, 95% CI=1.0001-1.003), likes
      (baseline: OR=1.001, 95% CI=1.0001-1.002 and sustainability: OR=1.0031, 95%
      CI=1.0003-1.002), and replies (baseline: OR=1.02, 95% CI=1.005-1.04 and
      sustainability: OR=1.02, 95% CI=1.004-1.03). At the network level, users with the
      least followers, tweets, retweets, and replies had the greatest reach.
      CONCLUSIONS: Reach was reduced by time. Factors increasing reach at the user
      level had different impact at the network level. More than one strategy is needed
      to maximize reach.

PMID- 30213783
TI  - Diagnostic Biomarkers: Are We Moving from Discovery to Clinical Application?
AB  - BACKGROUND: Despite considerable research investment, moving from biomarker
      discovery to clinical application has presented unique challenges. We aimed to
      evaluate progress toward clinical application of a sample of molecular- and
      "omics"-based diagnostic tests over a 10-year period. METHODS: We used Scopus to
      locate studies, published before the December 31, 2016, citing 107 original
      research articles published in 2006 that assessed the diagnostic value of a
      molecular- or "omics"-based test. We identified diagnostic studies of the same
      test and disease and determined whether the article represented progress in the
      validation of the molecular test. We classified the types of progress: (a)
      clinical validation (measuring diagnostic accuracy in a series of patients
      similar to the population in which the test will be used in practice), (b)
      technical improvement, (c) extended diagnostic application (modification of the
      diagnostic question attended initially by the test), (d) economic evaluation, or
      (e) clinical use or implementation. RESULTS: In the 10-year period analyzed, 4257
      articles cited the 107 diagnostic studies; 118 (2.8%) were diagnostic studies of
      the same test, and of these papers, 25 (21.2%) did not constitute progress toward
      validation of the test for use in clinical practice (potential research waste).
      Of the 107 molecular- or "omics"-based tests described in 2006, only 28 (26.2%)
      appeared to have made progress toward clinical application. Only 4 (9.1%) of 44
      proteomics-based tests had made progress toward clinical application.
      CONCLUSIONS: Articles evaluating molecular- or "omics"-based diagnostic tests are
      numerous in biomedical journals. Few tests have made progress toward clinical
      application in the 10 years following their discovery.

PMID- 30213785
TI  - Ireland's cervical cancer screening system was "doomed to fail," inquiry finds.

PMID- 30213784
TI  - Endothelin-1 Measurement in Patients Undergoing Diagnostic Coronary Angiography
      Results from the Catheter Sampled Blood Archive in Cardiovascular Diseases
      (CASABLANCA) Study.
AB  - BACKGROUND: Endothelin-1 (ET-1) is a vasoconstrictor produced by vascular
      endothelial cells and may play a role in risk for development of coronary artery
      disease (CAD) and heart failure (HF). In a cohort of 1084 patients referred for
      coronary angiography, we investigated cross-sectional associations between ET-1
      concentrations and prevalent CAD, as well as value of ET-1 for prognostication of
      future cardiovascular events. METHODS: Associations between ET-1 and
      presence/severity of CAD were assessed. Patients were followed for a median of 4
      years for outcomes including incident HF, myocardial infarction (MI),
      cardiovascular mortality, and all-cause mortality. RESULTS: The median
      concentration of ET-1 was 2.57 ng/L. Patients with ET-1 concentrations above the
      median were more likely to have higher risk clinical features. Among those
      without prevalent MI at presentation, ET-1 concentrations were not associated
      with presence or severity of CAD. In adjusted Cox proportional hazards analyses,
      log-transformed ET-1 concentrations predicted incident HF [hazard ratio (HR) =
      1.51 per increase in log-SD; 95% CI, 1.06-2.15; P = 0.02] and all-cause mortality
      (HR = 1.61 per increase in log-SD; 95% CI, 1.03-2.53; P = 0.04). Concentrations
      of ET-1 above the median were associated with shorter time to incident HF, MI,
      cardiovascular mortality, all-cause mortality, and the composite of incident
      HF/MI/cardiovascular mortality (all log-rank P < 0.001). CONCLUSIONS: Despite
      epidemiologic links to CAD, we found no cross-sectional association between
      biologically active ET-1 and prevalent coronary atherosclerosis in an at-risk
      population referred for coronary angiography. Increased ET-1 concentrations
      independently predict incident HF and death and are associated with more near
      term cardiovascular events.

PMID- 30213782
TI  - Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health: A
      Scoping Review.
AB  - BACKGROUND AND OBJECTIVES: Per- and polyfluoroalkyl substances (PFASs) are a
      large group of manufactured nonbiodegradable compounds. Despite increasing
      awareness as global pollutants, the impact of PFAS exposure on human health is
      not well understood, and there are growing concerns for adverse effects on kidney
      function. Therefore, we conducted a scoping review to summarize and identify gaps
      in the understanding between PFAS exposure and kidney health. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We systematically searched PubMed, EMBASE, EBSCO
      Global Health, World Health Organization Global Index, and Web of Science for
      studies published from 1990 to 2018. We included studies on the epidemiology,
      pharmacokinetics, or toxicology of PFAS exposure and kidney-related health,
      including clinical, histologic, molecular, and metabolic outcomes related to
      kidney disease, or outcomes related to the pharmacokinetic role of the kidneys.
      RESULTS: We identified 74 studies, including 21 epidemiologic, 13
      pharmacokinetic, and 40 toxicological studies. Three population-based
      epidemiologic studies demonstrated associations between PFAS exposure and lower
      kidney function. Along with toxicology studies (n=10) showing tubular histologic
      and cellular changes from PFAS exposure, pharmacokinetic studies (n=5)
      demonstrated the kidneys were major routes of elimination, with active proximal
      tubule transport. In several studies (n=17), PFAS exposure altered several
      pathways linked to kidney disease, including oxidative stress pathways,
      peroxisome proliferators-activated receptor pathways, NF-E2-related factor 2
      pathways, partial epithelial mesenchymal transition, and enhanced endothelial
      permeability through actin filament modeling. CONCLUSIONS: A growing body of
      evidence portends PFASs are emerging environmental threats to kidney health; yet
      several important gaps in our understanding still exist.

PMID- 30213786
TI  - Methylation and Expression of Nonclustered Protocadherins Encoding Genes and Risk
      of Precancerous Gastric Lesions in a High-Risk Population.
AB  - Nonclustered protocadherins (PCDH) family is a group of cell-cell adhesion
      molecules. We have found differentially methylated genes in the nonclustered
      PCDHs family associated with Helicobacter pylori (H. pylori) infection in prior
      genome-wide methylation analysis. To further investigate the methylation and
      expression of nonclustered PCDHs encoding genes in H. pylori--related gastric
      carcinogenesis process, four candidate genes including PCDH7, PCDH10, PCDH17, and
      PCDH20 were selected, which were reported to be tumor suppressors for digestive
      cancers. A total of 747 participants with a spectrum of gastric lesions were
      enrolled from a high-risk population of gastric cancer. Promoter methylation
      levels of four genes were significantly higher in H. pylori-positive subjects
      than the negative group (all P < 0.001). Elevated methylation levels of PCDH10
      and PCDH17 were observed with the increasing severity of gastric lesions (both P
      trend < 0.001). In the protein expression analysis, PCDH17 expression was
      inversely associated with gastric lesions; the OR [95% confidence interval (CI)]
      was 0.49 (0.26-0.95) for chronic atrophic gastritis (CAG), 0.31 (0.15-0.63) for
      intestinal metaplasia, and 0.38 (0.19-0.75) for indefinite dysplasia and
      dysplasia, compared with superficial gastritis. In addition, PCDH10 expression
      was significantly lower in CAG (OR, 0.40; 95% CI, 0.24-0.68). The inverse
      association between methylation and protein expression of PCDH10 and PCDH17 was
      further supported when we explored the methylation and mRNA expression in The
      Cancer Genome Atlas database (all P < 0.001). Our study found elevated promoter
      methylation and decreased expression of PCDH10 and PCDH17 in advanced gastric
      lesions, suggesting that elevated PCDH10 and PCDH17 methylation may be an early
      event in gastric carcinogenesis. Cancer Prev Res; 11(11); 717-26. (c)2018 AACR.

PMID- 30213788
TI  - Nedd4-Binding Protein 1 and TNFAIP3-Interacting Protein 1 Control MHC-1 Display
      in Neuroblastoma.
AB  - : Neuroblastoma is the second most common tumor in children. The cause of
      neuroblastoma is thought to lie in aberrant development of embryonic neural crest
      cells and is accompanied by low MHC-1 expression and suppression of the NF-kappaB
      transcription factor, thereby gearing cells toward escape from
      immunosurveillance. Here, we assess regulation of the MHC-1 gene in neuroblastoma
      to enhance its immunogenic potential for therapeutic T-cell targeting. A genome
      wide CRISPR screen identified N4BP1 and TNIP1 as inhibitory factors of NF-kappaB
      mediated MHC-1 expression in neuroblastoma. Patients with advanced stage
      neuroblastoma who expressed high levels of TNIP1 and N4BP1 exhibited worse
      overall survival. Depletion of N4BP1 or TNIP1 increased NF-kappaB and MHC-1
      expression and stimulated recognition by antigen-specific CD8+ T cells. We
      confirmed that TNIP1 inhibited canonical NF-kappaB member RelA by preventing
      activation of the RelA/p50 NF-kappaB dimer. Furthermore, N4BP1 inhibited both
      canonical and noncanonical NF-kappaB through binding of deubiquitinating enzyme
      CEZANNE, resulting in stabilization of TRAF3 and degradation of NF-kappaB
      inducing kinase NIK. These data suggest that N4BP1/CEZANNE or TNIP1 may be
      candidate targets for immunotherapy in neuroblastoma tumors and should lift NF
      kappaB suppression, thereby triggering increased peptide/MHC1-mediated tumor
      reactivity to enhance therapeutic T-cell targeting. SIGNIFICANCE: Aberrant
      regulation of NF-kappaB and MHC-1 in neuroblastoma tumors provides new targets
      for immunotherapeutic approaches against neuroblastoma.

PMID- 30213789
TI  - Seven days in medicine: 5-11 September 2018.

PMID- 30213787
TI  - B cells with aberrant activation of Notch1 signaling promote Treg and Th2 cell
      dominant T-cell responses via IL-33.
AB  - The Notch-signaling pathway in a variety of mature B-cell neoplasms is often
      activated by gene alterations, but its role remains unclear. Here, we show that B
      cells harboring dysregulated activation of Notch1 signaling have an
      immunomodulatory effect on T cells by amplifying regulatory T (Treg) and T helper
      2 (Th2) cell responses in an interleukin-33 (IL-33)-dependent manner. A
      conditional mouse model, in which constitutive expression of an active form of
      Notch1 is induced in B cells by Aicda gene promoter-driven Cre recombinase,
      revealed no obvious phenotypic changes in B cells; however, mice demonstrated an
      expansion of Treg and Th2 cell subsets and a decrease in cytokine production by
      Th1 and CD8+ T cells. The mice were susceptible to soft tissue sarcoma and
      defective production of CD8+ T cells specific for inoculated tumor cells,
      suggesting impaired antitumor T-cell activity. Gene-expression microarray
      revealed that altered T-cell responses were due to increased IL-33 production by
      Notch1-activated B cells. Knockout of IL33 or blockade of IL-33 by a receptor
      blocking antibody abrogated the Treg and Th2 cell-dominant T-cell response
      triggered by B cells. Gene-expression data derived from human diffuse large B
      cell lymphoma (DLBCL) samples showed that an activated Notch-signaling signature
      correlates positively with IL33 expression and Treg cell-rich gene-expression
      signatures. These findings indicate that B cells harboring dysregulated Notch
      signaling alter T-cell responses via IL-33, and suggest that aberrant activation
      of Notch signaling plays a role in fostering immune privilege in mature B-cell
      neoplasms.

PMID- 30213791
TI  - Development and validation of lifestyle-based models to predict incidence of the
      most common potentially preventable cancers.
AB  - BACKGROUND: Most risk models for cancer are either specific to individual cancers
      or include complex or predominantly non-modifiable risk factors. METHODS: We
      developed lifestyle-based models for the five cancers for which the most cases
      are potentially preventable through lifestyle change in the UK (lung, colorectal,
      bladder, kidney and oesophageal for men and breast, lung, colorectal, endometrial
      and kidney for women). We selected lifestyle risk factors from the European Code
      against Cancer and obtained estimates of relative risks from meta-analyses of
      observational studies. We used mean values for risk factors from nationally
      representative samples and mean 10-year estimated absolute risks from routinely
      available sources. We then assessed the performance of the models in 23,768
      participants in the EPIC-Norfolk cohort who had no history of the five selected
      cancers at baseline. RESULTS: In men the combined risk model showed good
      discrimination (AUC: 0.71, 95% CI 0.69-0.73) and calibration. Discrimination was
      lower in women (AUC: 0.59 95% CI 0.57 - 0.61) but calibration was good. In both
      sexes the individual models for lung cancer had the highest AUCs (0.83, 95%CI
      0.80-0.85 for men and 0.82, 95%CI 0.76-0.87 for women). The lowest AUCs were for
      breast cancer in women and kidney cancer in men. CONCLUSIONS: The discrimination
      and calibration of the models are both reasonable, with the discrimination for
      individual cancers comparable or better than many other published risk models.
      IMPACT: These models could be used to demonstrate the potential impact of
      lifestyle change on risk of cancer to promote behaviour change.

PMID- 30213792
TI  - Clinically assisted nutrition and hydration.

PMID- 30213793
TI  - Marketing e-cigarettes to kids has created an "epidemic" in US, says FDA chief.

PMID- 30213790
TI  - The cytochrome P450 CYP77A4 is involved in auxin-mediated patterning of the
      Arabidopsis thaliana embryo.
AB  - Metabolism often plays an important role in developmental control, in addition to
      supporting basal physiological requirements. However, our understanding of this
      interaction remains limited. Here, we performed quantitative phenome analysis of
      Arabidopsis thaliana cytochrome P450 mutants to identify a novel interaction
      between development and metabolism. We found that cyp77a4 mutants exhibit
      specific defects in cotyledon development, including asymmetric positioning and
      cup-shaped morphology, which could be rescued by introducing the CYP77A4 gene.
      Microscopy revealed that the abnormal patterning was detected at least from the 8
      cell stage of the cyp77a4 embryos. We next analysed auxin distribution in mutant
      embryos, as the phenotypes resembled those of auxin-related mutants. We found
      that the auxin response pattern was severely perturbed in the cyp77a4 embryos
      owing to an aberrant distribution of the auxin efflux carrier PIN1. CYP77A4
      intracellularly localised to the endoplasmic reticulum, which is consistent with
      the notion that this enzyme acts as an epoxidase of unsaturated fatty acids in
      the microsomal fraction. We propose that the CYP77A4-dependent metabolic pathway
      is an essential element for the establishment of polarity in plant embryos.

PMID- 30213794
TI  - Correction: Renal scar formation and kidney function following antibiotic-treated
      murine pyelonephritis (doi: 10.1242/dmm.030130).

PMID- 30213795
TI  - SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity.
AB  - Glioblastoma is one of the most aggressive forms of cancers and has a poor
      prognosis. Genomewide analyses have revealed that a set of core signaling
      pathways, the p53, RB, and RTK pathways, are commonly deregulated in
      glioblastomas. However, the molecular mechanisms underlying the tumorigenicity of
      glioblastoma are not fully understood. Here, we show that the lysine deacetylase
      SIRT2 is required for the proliferation and tumorigenicity of glioblastoma cells,
      including glioblastoma stem cells. Furthermore, we demonstrate that SIRT2
      regulates p73 transcriptional activity by deacetylation of its C-terminal lysine
      residues. Our results suggest that SIRT2-mediated inactivation of p73 is critical
      for the proliferation and tumorigenicity of glioblastoma cells and that SIRT2 may
      be a promising molecular target for the therapy of glioblastoma.

PMID- 30213797
TI  - Reversal of Triple-Negative Breast Cancer EMT by miR-200c Decreases Tryptophan
      Catabolism and a Program of Immunosuppression.
AB  - Tryptophan-2,3-dioxygenase (TDO2), a rate-limiting enzyme in the tryptophan
      catabolism pathway, is induced in triple-negative breast cancer (TNBC) by
      inflammatory signals and anchorage-independent conditions. TNBCs express
      extremely low levels of the miR-200 family compared with estrogen receptor
      positive (ER+) breast cancer. In normal epithelial cells and ER+ breast cancers
      and cell lines, high levels of the family member miR-200c serve to target and
      repress genes involved in epithelial-to-mesenchymal transition (EMT). To identify
      mechanism(s) that permit TNBC to express TDO2 and other proteins not expressed in
      the more well-differentiated ER+ breast cancers, miRNA-200c was restored in TNBC
      cell lines. The data demonstrate that miR-200c targeted TDO2 directly resulting
      in reduced production of the immunosuppressive metabolite kynurenine.
      Furthermore, in addition to reversing a classic EMT signature, miR-200c repressed
      many genes encoding immunosuppressive factors including CD274/CD273, HMOX-1, and
      GDF15 Restoration of miR-200c revealed a mechanism, whereby TNBC hijacks a gene
      expression program reminiscent of that used by trophoblasts to suppress the
      maternal immune system to ensure fetal tolerance during pregnancy.Implications:
      Knowledge of the regulation of tumor-derived immunosuppressive factors will
      facilitate development of novel therapeutic strategies that complement current
      immunotherapy to reduce mortality for patients with TNBC. Mol Cancer Res; 1-12.
      (c)2018 AACR.

PMID- 30213796
TI  - FLOWERING LOCUS T3 Controls Spikelet Initiation But Not Floral Development.
AB  - In many angiosperm plants, FLOWERING LOCUS T (FT)-like genes have duplicated and
      functionally diverged to control different reproductive traits or stages. Barley
      (Hordeum vulgare) carries several FT-like genes, the functions of which are not
      well understood. We characterized the role of HvFT3 in the vegetative and
      reproductive development of barley. Overexpression of HvFT3 accelerated the
      initiation of spikelet primordia and the early reproductive development of spring
      barley independently of the photoperiod. However, HvFT3 overexpression did not
      accelerate floral development, and inflorescences aborted under short days,
      suggesting that HvFT3 controls spikelet initiation but not floral development.
      Analysis of a nonfunctional HvFT3 allele supported the specific effects of this
      gene on spikelet initiation independent of the photoperiod. HvFT3 caused the up
      regulation of the winter and spring alleles of the vernalization gene
      VERNALIZATION1 (VRN-H1) in nonvernalized plants and was therefore dominant over
      the repressive effects of the vernalization pathway. Global transcriptome
      analysis in developing main shoot apices of the transgenic lines showed that
      HvFT3 modified the expression of genes involved in hormone synthesis and
      response, of floral homeotic genes, and of barley row-type genes SIX-ROWED-SPIKE1
      (VRS1), SIX-ROWED-SPIKE4 (VRS4), and INTERMEDIUM C Understanding the specific
      functions of individual FT-like genes will allow modification of individual
      phases of preanthesis development and thereby adaptation to different
      environments and improved yield.

PMID- 30213799
TI  - Mental health: 50 organisations vow to win back years of patients' lost physical
      health.

PMID- 30213798
TI  - A New Mobile Application to Reduce Anxiety in Pediatric Patients Before Bone
      Marrow Aspiration Procedures.
AB  - OBJECTIVES: Insufficient preparation for children who are undergoing bone marrow
      aspiration can cause anxiety and negative outcomes. Nonpharmacological therapies
      have been proven to reduce fear in children who are undergoing painful
      procedures. We have therefore developed a mobile application to help reduce these
      patients' anxiety by providing them with procedural information and coping
      skills. METHODS: This single-blinded, randomized controlled trial included 60
      patients age 5 to 12 years old who were undergoing bone marrow aspiration
      procedures in Thailand that were conducted between May 2015 and May 2016. Sixty
      participants were randomly assigned to the intervention group (mobile application
      added to usual care) or the control group (usual care only). Preprocedural
      anxiety levels were evaluated by visual analog scales (child anxiety visual
      analog scale); this was repeated in the intervention group immediately after
      patients used the mobile application. On the day of the procedure, the patients'
      cooperation levels were assessed by using the modified Yale Preoperative Anxiety
      Scale. The total amount of sedative drugs that were used was also recorded. The
      paired t test and the Wilcoxon signed rank test were used to analyze within
      person change, whereas the t test and the Wilcoxon rank sum test were used for
      group comparisons. RESULTS: The child anxiety visual analog scale score of
      patients in the intervention group decreased significantly after they used the
      mobile application (P < .0012). The modified Yale Preoperative Anxiety Scale
      score of patients in the intervention group was significantly lower than that in
      the control group (P < .01). There was no difference in sedative use between the
      2 groups. CONCLUSIONS: This mobile application possibly had effectiveness in
      routine use for reducing anxiety and increasing patients' cooperation in bone
      marrow aspiration procedures.

PMID- 30213801
TI  - Might children rust? What are the risks of supplemental oxygen in acute illness.

PMID- 30213800
TI  - Cholesterol efflux responds to viral load and CD4 counts in HIV+ patients and is
      dampened in HIV exposed.
AB  - Cholesterol efflux (CE) capacity has been inversely associated with
      atherosclerosis and may provide an insight on inflammation occurring in human
      immunodeficiency virus (HIV) individuals. We address this by studying CE in HIV
      patients at different stages of HIV disease progression. In this cross-sectional
      study, CE from ApoB-depleted plasma, lipids levels, viral load (VL), CD4+/CD8+ T
      cells, high-sensitive C-reactive protein (hsCRP), and lipoprotein (a) were
      evaluated in untreated HIV-infected patients (UHIVs; n = 43), elite controllers
      (ECs; n = 8), HIV-exposed seronegative individuals (HESNs; n = 32), and healthy
      controls (HCs; n = 14). Among UHIVs, those with CD4+ <500 cells/mm3 presented the
      lowest significant CE, HDL cholesterol (HDL-C), and ApoAI levels. ECs showed
      similar HDL-C, ApoAI, and CE compared with HCs. Among UHIVs, CE positively
      correlated with CD4+ T-cell counts (Beta: 1.05; 95% CI: 1.02; 1.07), and for VL
      higher than 3.8 log, CE was inversely associated with VL (Beta: 0.70; 95% CI:
      0.51; 0.95). Remarkably, HESNs presented higher CE (0.78 +/- 0.14) than UHIVs
      (0.65 +/- 0.17; P = 0.0005), but lower than HCs (0.90 +/- 0.13; P = 0.009). hsCRP
      levels were highest in the UHIV group (0.45 +/- 0.49). CE was sensitive to HIV
      disease progression. Low CE in HIV patients was associated with lower CD4+ T
      cells and higher VL and hsCRP. CE was also lower in HESNs compared with HCs. Our
      results suggest that immune status secondary to HIV progression and exposure
      influence plasma HDL-CE capacity.

PMID- 30213802
TI  - Utility of an "Allosteric Site-Impaired" M2 Muscarinic Acetylcholine Receptor as
      a Novel Construct for Validating Mechanisms of Action of Synthetic and Putative
      Endogenous Allosteric Modulators.
AB  - Muscarinic acetylcholine receptors (mAChRs) are exemplar models for understanding
      G protein-coupled receptor (GPCR) allostery, possessing a "common" allosteric
      site in an extracellular vestibule (ECV) for synthetic modulators including
      gallamine, strychnine, and brucine. In addition, there is intriguing evidence of
      endogenous peptides/proteins that may target this region at the M2 mAChR. A
      common feature of synthetic and endogenous M2 mAChR negative allosteric
      modulators (NAMs) is their cationic nature. Using a structure-based approach, we
      previously designed a mutant M2 mAChR (N410K+T423K) to specifically abrogate
      binding of ECV cationic modulators (Dror et al., 2013). Herein, we used this
      "allosteric site-impaired" receptor to investigate allosteric interactions of
      synthetic modulators as well as basic peptides (poly-l-arginine, endogenously
      produced protamine, and major basic protein). Using [3H]N-methylscopolamine
      equilibrium and kinetic binding and functional assays of guanosine 5'-O-[gamma
      thio]triphosphate [35S] binding and extracellular signal-regulated kinases 1 and
      2 phosphorylation, we found modest effects of the mutations on potencies of
      orthosteric antagonists and an increase in the affinity of the cognate agonist,
      acetylcholine, likely reflecting the effect of the mutations on the access/egress
      of these ligands into the orthosteric pocket. More importantly, we noted a
      significant abrogation in affinity for all synthetic or peptidic modulators at
      the mutant mAChR, validating their allosteric nature. Collectively, these
      findings provide evidence for a hitherto-unappreciated role of endogenous
      cationic peptides interacting allosterically at the M2 mAChR and identify the
      allosteric site-impaired GPCR as a tool for validating NAM activity as well as a
      potential candidate for future chemogenetic strategies to understand the
      physiology of endogenous allosteric substances.

PMID- 30213804
TI  - Spinal Instrumentation Rescue with Cement Augmentation.
AB  - BACKGROUND AND PURPOSE: Altered biomechanics or bone fragility or both contribute
      to spine instrumentation failure. Although revision surgery is frequently
      required, minimally invasive alternatives may be feasible. We report the largest
      to-date series of percutaneous fluoroscopically guided vertebral cement
      augmentation procedures to address feasibility, safety, results and a variety of
      spinal instrumentation failure conditions. MATERIALS AND METHODS: A consecutive
      series of 31 fluoroscopically guided vertebral augmentation procedures in 29
      patients were performed to address screw loosening (42 screws), cage subsidence
      (7 cages), and fracture within (12 cases) or adjacent to (11 cases) the
      instrumented segment. Instrumentation failure was deemed clinically relevant when
      resulting in pain or jeopardizing spinal biomechanical stability. The main study
      end point was the rate of revision surgery avoidance; feasibility and safety were
      assessed by prospective recording of periprocedural technical and clinical
      complications; and clinical effect was measured at 1 month with the Patient
      Global Impression of Change score. RESULTS: All except 1 procedure was
      technically feasible. No periprocedural complications occurred. Clinical and
      radiologic follow-up was available in 28 patients (median, 16 months) and 30
      procedures. Revision surgery was avoided in 23/28 (82%) patients, and a global
      clinical benefit (Patient Global Impression of Change, 5-7) was reported in 26/30
      (87%) cases at 1-month follow-up, while no substantial change (Patient Global
      Impression of Change, 4) was reported in 3/30 (10%), and worsening status
      (Patient Global Impression of Change, 3), in 1/30 (3%). CONCLUSIONS: Our
      experience supports the feasibility of percutaneous vertebral augmentation in the
      treatment of several clinically relevant spinal instrumentation failure
      conditions, with excellent safety and efficacy profiles, both in avoidance of
      revision surgery and for pain palliation.

PMID- 30213803
TI  - Automated Integration of Multimodal MRI for the Probabilistic Detection of the
      Central Vein Sign in White Matter Lesions.
AB  - BACKGROUND AND PURPOSE: The central vein sign is a promising MR imaging
      diagnostic biomarker for multiple sclerosis. Recent studies have demonstrated
      that patients with MS have higher proportions of white matter lesions with the
      central vein sign compared with those with diseases that mimic MS on MR imaging.
      However, the clinical application of the central vein sign as a biomarker is
      limited by interrater differences in the adjudication of the central vein sign as
      well as the time burden required for the determination of the central vein sign
      for each lesion in a patient's full MR imaging scan. In this study, we present an
      automated technique for the detection of the central vein sign in white matter
      lesions. MATERIALS AND METHODS: Using multimodal MR imaging, the proposed method
      derives a central vein sign probability, piij, for each lesion, as well as a
      patient-level central vein sign biomarker, psii. The method is probabilistic in
      nature, allows site-specific lesion segmentation methods, and is potentially
      robust to intersite variability. The proposed algorithm was tested on imaging
      acquired at the University of Vermont in 16 participants who have MS and 15
      participants who do not. RESULTS: By means of the proposed automated technique,
      participants with MS were found to have significantly higher values of psi than
      those without MS (psiMS = 0.55 +/- 0.18; psinon-MS = 0.31 +/- 0.12; P < .001).
      The algorithm was also found to show strong discriminative ability between
      patients with and without MS, with an area under the curve of 0.88. CONCLUSIONS:
      The current study presents the first fully automated method for detecting the
      central vein sign in white matter lesions and demonstrates promising performance
      in a sample of patients with and without MS.

PMID- 30213805
TI  - Correlation between Human Papillomavirus Status and Quantitative MR Imaging
      Parameters including Diffusion-Weighted Imaging and Texture Features in
      Oropharyngeal Carcinoma.
AB  - BACKGROUND AND PURPOSE: The incidence of Oropharyngeal Squampus Cell Carcinoma
      (OPSCC) cases is increasing especially in the Western countries due to the
      spreading of human papilloma virus (HPV) infection. Radiological investigations,
      MRI in particular, are used in the daily clinical practice to stage OPSCC. The
      aim of this study was to investigate the association of quantitative MR imaging
      features including diffusion-weighted imaging and human papillomavirus status in
      oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: We retrospectively
      analyzed 59 patients with untreated histologically proved T2-T4 oropharyngeal
      squamous cell carcinoma. Human papillomavirus status was determined by viral DNA
      detection on tissue samples. MR imaging protocol included T2-weighted, contrast
      enhanced T1-weighted (volumetric interpolated brain examination), and DWI
      sequences. Parametric maps of apparent diffusion coefficient were obtained from
      DWI sequences. Texture analysis was performed on T2 and volumetric-interpolated
      brain examination sequences and on ADC maps. Differences in quantitative MR
      imaging features between tumors positive and negative for human papillomavirus
      and among subgroups of patients stratified by smoking status were tested using
      the nonparametric Mann-Whitney U test; the false discovery rate was controlled
      using the Benjamini-Hochberg correction; and a predictive model for human
      papillomavirus status was built using multivariable logistic regression. RESULTS:
      Twenty-eight patients had human papillomavirus-positive oropharyngeal squamous
      cell carcinoma, while 31 patients had human papillomavirus-negative oropharyngeal
      squamous cell carcinoma. Tumors positive for human papillomavirus had a
      significantly lower mean ADC compared with those negative for it (median, 850.87
      versus median, 1033.68; P < .001). Texture features had a lower discriminatory
      power for human papillomavirus status. Skewness on volumetric interpolated brain
      examination sequences was significantly higher in the subgroup of patients
      positive for human papillomavirus and smokers (P = .003). A predictive model
      based on smoking status and mean ADC yielded a sensitivity of 83.3% and
      specificity 92.6% in classifying human papillomavirus status. CONCLUSIONS: ADC is
      significantly lower in oropharyngeal squamous cell carcinoma positive for human
      papillomavirus compared with oropharyngeal squamous cell carcinoma negative for
      it. ADC and smoking status allowed noninvasive prediction of human papillomavirus
      status with a good accuracy. These results should be validated and further
      investigated on larger prospective studies.

PMID- 30213806
TI  - CT versus MR Imaging in Estimating Cochlear Radiation Dose during Gamma Knife
      Surgery for Vestibular Schwannomas.
AB  - BACKGROUND AND PURPOSE: Leksell stereotactic radiosurgery is an effective option
      for patients with vestibular schwannomas. Some centers use a combination of
      stereotactic CT fused with stereotactic MR imaging to achieve an optimal target
      definition as well as minimize the radiation dose delivered to adjacent
      structures that correlate with hearing outcomes. The present prospective study
      was designed to determine whether there is cochlear dose variability between MR
      imaging and CT. MATERIALS AND METHODS: Fifty consecutive patients underwent
      stereotactic radiosurgery for vestibular schwannomas. Dose-planning was performed
      using high-definition fused stereotactic MR imaging and stereotactic CT images.
      The 3D cochlear volume was determined by delineating the cochlea on both CT and
      T2-weighted MR imaging. The mean radiation dose, maximum dose, and 3- and 4.20-Gy
      cochlear volumes were identified using standard Leksell Gamma Knife software.
      RESULTS: The median mean radiation dose delivered to the cochlea was 3.50 Gy
      (range, 1.20-6.80 Gy) on CT and 3.40 Gy (range, 1-6.70 Gy) on MR imaging
      (concordance correlation coefficient = 0.86, r 2 = 0.9, P <= .001). The median
      maximum dose delivered to the cochlea was 6.7 Gy on CT and 6.6 Gy on MR imaging
      (concordance correlation coefficient = 0.89, r 2 = 0.90, P <= .001). Dose-volume
      histograms generated from CT and MR imaging demonstrated a strong level of
      correlation in estimating the 3- and 4.20-Gy volumes (concordance correlation
      coefficient = 0.81, r 2 = 0.82, P <= .001 and concordance correlation coefficient
      = 0.87, r 2 = 0.89, P <= .001). CONCLUSIONS: Both MR imaging and CT provide
      similar cochlear dose parameters. Despite the reported superiority of CT in
      identifying bony structures, high-definition MR imaging alone is sufficient to
      identify the radiation doses delivered to the cochlea.

PMID- 30213807
TI  - The Impact of Persistent Leukoencephalopathy on Brain White Matter Microstructure
      in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Chemotherapy
      Only.
AB  - BACKGROUND AND PURPOSE: Survivors of acute lymphoblastic leukemia are at risk for
      neurocognitive deficits and leukoencephalopathy. We performed a longitudinal
      assessment of leukoencephalopathy and its associations with long-term brain
      microstructural white matter integrity and neurocognitive outcomes in survivors
      of childhood acute lymphoblastic leukemia treated on a modern chemotherapy-only
      protocol. MATERIALS AND METHODS: One hundred seventy-three survivors of acute
      lymphoblastic leukemia (49% female), treated on a chemotherapy-only protocol,
      underwent brain MR imaging during active therapy and repeat imaging and
      neurocognitive testing at follow-up (median, 13.5 years of age; interquartile
      range, 10.7-17.6 years; median time since diagnosis, 7.5 years; interquartile
      range, 6.3-9.1 years). Persistence of leukoencephalopathy was examined in
      relation to demographic and treatment data and to brain DTI in major fiber tracts
      and neurocognitive testing at follow-up. RESULTS: Leukoencephalopathy was found
      in 52 of 173 long-term survivors (30.0%) and persisted in 41 of 52 (78.8%) who
      developed it during therapy. DTI parameters were associated with
      leukoencephalopathy in multiple brain regions, including the corona radiata
      (fractional anisotropy, P = .001; mean diffusivity, P < .001), superior
      longitudinal fasciculi (fractional anisotropy, P = .02; mean diffusivity, P <
      .001), and superior fronto-occipital fasciculi (fractional anisotropy, P = .006;
      mean diffusivity, P < .001). Mean diffusivity was associated with neurocognitive
      impairment including in the genu of the corpus callosum (P = .04), corona radiata
      (P = .02), and superior fronto-occipital fasciculi (P = .02). CONCLUSIONS:
      Leukoencephalopathy during active therapy and neurocognitive impairment at long
      term follow-up are associated with microstructural white matter integrity. DTI
      may be more sensitive than standard MR imaging for detection of clinically
      consequential white matter abnormalities in childhood acute lymphoblastic
      leukemia survivors treated with chemotherapy and in children undergoing
      treatment.

PMID- 30213808
TI  - Multidelay Arterial Spin-Labeling MRI in Neonates and Infants: Cerebral Perfusion
      Changes during Brain Maturation.
AB  - BACKGROUND AND PURPOSE: Arterial spin-labeling with multiple postlabeling delays
      can correct transit times. We tried to evaluate CBF in neonates and infants using
      multidelay arterial spin-labeling. MATERIALS AND METHODS: Multidelay arterial
      spin-labeling was applied to 13 preterm neonates (mean postmenstrual age, 34.9
      weeks), 13 term-equivalent-age neonates (mean postmenstrual age, 39.2 weeks), and
      6 infants (mean postmenstrual age, 57.8 weeks). Transit time-corrected CBF in the
      caudate, thalamus, frontal GM, occipital GM, frontal WM, and occipital WM was
      measured, and relative CBF compared with the whole-brain CBF was calculated.
      Inter- and intragroup comparisons were performed among the 3 age groups. A
      correlation and nonlinear regression analysis were performed between
      postmenstrual age and CBF. RESULTS: Intergroup comparisons showed significantly
      higher whole-brain CBF in infants (38.3 mL/100 g/min) compared with preterm (15.5
      mL/100 g/min) and term-equivalent-age (18.3 mL/100 g/min) neonates (P < .001). In
      the intragroup comparison, all 3 groups showed significantly higher relative CBF
      values in the occipital WM (63.6%-90.3%) compared with the frontal WM (46.3%
      73.9%). In term-equivalent-age neonates, the occipital GM (120.8%) had
      significantly higher relative CBF values than the frontal GM (103.5%). There was
      a significant negative correlation between postmenstrual age and the relative CBF
      of the thalamus (r = - 0.449, P = .010). There were significant positive
      relationships between postmenstrual age and the relative CBF of the frontal WM (R
      2 = 0.298, P = .001) and occipital WM (R 2 = 0.452, P < .001). CONCLUSIONS:
      Multidelay arterial spin-labeling with transit time-corrected CBF showed
      developmental changes and regional differences of CBF in neonates and infants.

PMID- 30213809
TI  - The Diagnostic Value of Diffusion-Weighted Imaging in Differentiating Metastatic
      Lymph Nodes of Head and Neck Squamous Cell Carcinoma: A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: Accurate lymph node staging is crucial for proper treatment planning
      for metastasis in patients with head and neck squamous cell carcinoma. PURPOSE:
      Our aim was to evaluate the diagnostic performance of DWI for differentiating
      metastatic cervical lymph nodes from benign cervical lymph nodes in patients with
      head and neck squamous cell carcinoma and to identify optimal cutoff values for
      ADC. DATA SOURCES: A computerized literature search was performed to identify
      relevant original articles in Ovid MEDLINE and EMBASE. STUDY SELECTION: Studies
      evaluating the diagnostic performance of DWI for differentiating metastatic
      cervical lymph nodes from benign cervical lymph nodes were selected. DATA
      ANALYSIS: Diagnostic meta-analysis was conducted with a bivariate random-effects
      model, and a hierarchical summary receiver operating characteristic curve was
      obtained. Meta-regression was also performed. DATA SYNTHESIS: Nine studies with
      337 patients were included. In all studies, ADC values derived from metastatic
      lymph nodes were significantly lower than ADC values derived from benign lymph
      nodes. The median ADC cutoff value was 0.965 * 10-3 mm2/s. The pooled sensitivity
      and specificity for the diagnostic performance of DWI in differentiating
      metastatic lymph nodes from benign lymph nodes were 90% (95% CI, 84%-94%) and 88%
      (95% CI, 80%-93%), respectively. In the meta-regression, sensitivity was
      significantly higher in the studies using a 3-mm slice thickness (93% [95% CI,
      88%-98%]) than in studies using a slice thickness of >3 mm (86% [95% CI, 77%
      95%], P < .01). LIMITATIONS: A small number of studies were included in our meta
      analysis. CONCLUSIONS: DWI demonstrated high diagnostic performance for
      differentiating metastatic lymph nodes from benign lymph nodes in patients with
      head and neck squamous cell carcinoma, and the median ADC cutoff value was 0.965
      * 10-3 mm2/s. A 3-mm DWI slice thickness can provide a slight improvement in
      sensitivity.

PMID- 30213810
TI  - Longitudinal Findings of MRI and PET in West Syndrome with Subtle Focal Cortical
      Dysplasia.
AB  - BACKGROUND AND PURPOSE: Despite the development of neuroimaging, identification
      of focal cortical dysplasia remains challenging. The purpose of this study was to
      show the longitudinal changes of MR imaging and FDG-PET in patients with West
      syndrome and subtle focal cortical dysplasia. MATERIALS AND METHODS: Among 52
      consecutive patients with West syndrome, 4 were diagnosed with subtle focal
      cortical dysplasia on 3T MR imaging. MR imaging and PET findings were evaluated
      longitudinally at onset and at 12 and 24 months of age. RESULTS: At the onset of
      West syndrome, MR imaging demonstrated focal signal abnormalities of the
      subcortical white matter in 2 patients. In the other 2 patients, focal
      subcortical high-intensity signals became visible on follow-up T2WI as
      myelination progressed. PET at onset showed focal cortical hypometabolism in 3
      patients, with 1 of these patients also having focal hypermetabolism and 1 having
      normal findings. On PET at 24 months, hypometabolism persisted in 2 patients and
      disappeared in 1, and hypermetabolism disappeared in 1. In 1 patient with normal
      MR imaging and PET findings at onset, focal hyperintensity and hypometabolism
      first appeared at 24 months of age. The findings on MR imaging and PET in these
      patients evolved differently with brain maturation and the clinical course.
      CONCLUSIONS: Subtle focal cortical dysplasia can be undetectable on MR imaging at
      the onset of West syndrome and is not always accompanied by hypometabolism or
      hypermetabolism on PET. Longitudinal MR imaging and PET studies may be useful for
      detecting such lesions. Even in West syndrome with a congenital structural
      abnormality, PET findings evolve differently with brain maturation and the
      clinical condition.

PMID- 30213811
TI  - Quantification of Blood Velocity with 4D Digital Subtraction Angiography Using
      the Shifted Least-Squares Method.
AB  - BACKGROUND AND PURPOSE: 4D-DSA provides time-resolved 3D-DSA volumes with high
      temporal and spatial resolutions. The purpose of this study is to investigate a
      shifted least squares method to estimate the blood velocity from the 4D DSA
      images. Quantitative validation was performed using a flow phantom with an
      ultrasonic flow probe as ground truth. Quantification of blood velocity in human
      internal carotid arteries was compared with measurements generated from 3D phase
      contrast MR imaging. MATERIALS AND METHODS: The centerlines of selected vascular
      segments and the time concentration curves of each voxel along the centerlines
      were determined from the 4D-DSA dataset. The temporal shift required to achieve a
      minimum difference between any point and other points along the centerline of a
      segment was calculated. The temporal shift as a function of centerline point
      position was fit to a straight line to generate the velocity. The proposed
      shifted least-squares method was first validated using a flow phantom study.
      Blood velocities were also estimated in the 14 ICAs of human subjects who had
      both 4D-DSA and phase-contrast MR imaging studies. Linear regression and
      correlation analysis were performed on both the phantom study and clinical study,
      respectively. RESULTS: Mean velocities of the flow phantom calculated from 4D-DSA
      matched very well with ultrasonic flow probe measurements with 11% relative root
      mean square error. Mean blood velocities of ICAs calculated from 4D-DSA
      correlated well with phase-contrast MR imaging measurements with Pearson
      correlation coefficient r = 0.835. CONCLUSIONS: The availability of 4D-DSA
      provides the opportunity to use the shifted least-squares method to estimate
      velocity in vessels within a 3D volume.

PMID- 30213812
TI  - Clinical Evaluation of Highly Accelerated Compressed Sensing Time-of-Flight MR
      Angiography for Intracranial Arterial Stenosis.
AB  - BACKGROUND AND PURPOSE: Time-of-flight MR angiography is the preferred imaging
      technique to assess intracranial arterial stenosis but is limited by a relatively
      long acquisition time. Compressed sensing provides an innovative approach in
      undersampling k-space to minimize the data-acquisition time. We aimed to evaluate
      the diagnostic accuracy of compressed sensing TOF for detecting intracranial
      arterial stenosis by comparison with conventional parallel imaging TOF-MRA.
      MATERIALS AND METHODS: Compressed sensing TOF and parallel imaging TOF were
      performed in 22 patients with intracranial arterial stenosis. The MRA scan times
      were 2 minutes and 31 seconds and 4 minutes and 48 seconds for compressed sensing
      TOF and parallel imaging TOF, respectively. The reconstructed resolutions were
      0.4 * 0.4 * 0.4 and 0.4 * 0.4 * 0.6 mm3 for compressed sensing TOF and parallel
      imaging TOF, respectively. The diagnostic quality of the images and visibility of
      the stenoses were independently ranked by 2 neuroradiologists blinded to the type
      of method and were compared using the Wilcoxon signed rank test. Concordance was
      calculated with the Cohen kappa. Edge sharpness of the arteries and the luminal
      stenosis ratio were analyzed and compared using a paired-sample t test. RESULTS:
      The interrater agreement was good to excellent. Compressed sensing TOF resulted
      in image quality comparable with that of parallel imaging TOF but boosted
      confidence in diagnosing arterial stenoses (P = .025). The edge sharpness of the
      intracranial arteries for compressed sensing TOF was significantly higher than
      that for parallel imaging TOF (P < .001). The luminal stenosis ratio on
      compressed sensing TOF showed no significant difference compared with that on
      parallel imaging TOF. CONCLUSIONS: Compressed sensing TOF both remarkably reduced
      the scan time and provided adequate image quality for the diagnosis of
      intracranial arterial stenosis.

PMID- 30213813
TI  - Longitudinal Persistence of Meningeal Enhancement on Postcontrast 7T 3D-FLAIR MRI
      in Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: Preliminary research has demonstrated that postgadolinium
      3D-FLAIR MR imaging at 7T may be a valuable tool for detecting abnormal meningeal
      enhancement and inflammation in MS; however, researchers have not systematically
      investigated its longitudinal persistence. We hypothesized that persistence of
      meningeal enhancement in MS varies on the basis of pattern of enhancement as well
      as demographic and clinical factors such as treatment status, disease phenotype,
      and disability score. MATERIALS AND METHODS: Thirty-one subjects with MS were
      prospectively scanned before and after intravenous contrast administration at 2
      time points, approximately 1 year apart. Fifteen subjects in the cohort were
      scanned at another time approximately 1 year later. Foci of enhancement were
      categorized into 4 subtypes: subarachnoid spread/fill, subarachnoid nodular,
      vessel wall, and dural foci. We reviewed follow-up scans to determine whether
      foci changed between time points and then compared persistence with demographic
      and clinical variables. RESULTS: Persistence ranged from 71% to 100% at 1 year
      and 73% to 100% at 2 years, depending on the enhancement pattern. Subarachnoid
      spread/fill and subarachnoid nodular subtypes persisted less often than vessel
      wall and dural foci. Persistence was not significantly different between those
      on/off treatment and those with progressive/nonprogressive disease phenotypes.
      The number of persisting foci was significantly different in subjects
      with/without increasing Expanded Disability Status Scale scores (median, 12
      versus 7.5, P = .04). CONCLUSIONS: Longitudinal persistence of meningeal
      enhancement on 3D-FLAIR at 7T in MS varies by pattern of enhancement and
      correlates with worsening disability; however, it is not significantly different
      in those on/off treatment or in those with progressive/nonprogressive disease
      phenotypes.

PMID- 30213814
TI  - Reply.

PMID- 30213815
TI  - Vertebroplasty: Expectation or Evidence-Based Interventional Radiology?

PMID- 30213816
TI  - Reply.

PMID- 30213817
TI  - Quality-Control Assessment to Improve the Accuracy of Dynamic Contrast-Enhanced
      MR Imaging Perfusion.

PMID- 30213818
TI  - Reply.

PMID- 30213819
TI  - MRI Findings Suggestive of Herpes Simplex Encephalitis in Patients with Anti-NMDA
      Receptor Encephalitis.

PMID- 30213820
TI  - Correction: Incident CTS in a large pooled cohort study: associations obtained by
      a Job Exposure Matrix versus associations obtained from observed exposures.

PMID- 30213821
TI  - Expression of Concern. Kathrin Maedler, Desiree M. Schumann, Fabienne Schulthess,
      Jose Oberholzer, Domenico Bosco, Thierry Berney, and Marc Y. Donath. Aging
      Correlates With Decreased beta-Cell Proliferative Capacity and Enhanced
      Sensitivity to Apoptosis: A Potential Role for Fas and Pancreatic Duodenal
      Homeobox-1. Diabetes 2006;55:2455-2462. DOI: 10.2337/db05-1586. PMID: 16936193.

PMID- 30213822
TI  - Update to Expression of Concern. Kathrin Maedler, Desiree M. Schumann, Nadine
      Sauter, Helga Ellingsgaard, Domenico Bosco, Reto Baertschiger, Yoichiro Iwakura,
      Jose Oberholzer, Claes B. Wollheim, Benoit R. Gauthier, and Marc Y. Donath. Low
      Concentration of Interleukin-1beta Induces FLICE-Inhibitory Protein-Mediated beta
      Cell Proliferation in Human Pancreatic Islets. Diabetes 2006;55:2713-2722.
      DOI:10.2337/db05-1430. PMID: 17003335.

PMID- 30213823
TI  - Lipoxins Protect Against Inflammation in Diabetes-Associated Atherosclerosis.
AB  - Increasing evidence points to the fact that defects in the resolution of
      inflammatory pathways predisposes individuals to the development of chronic
      inflammatory diseases, including diabetic complications such as accelerated
      atherosclerosis. The resolution of inflammation is dynamically regulated by the
      production of endogenous modulators of inflammation, including lipoxin A4 (LXA4).
      Here, we explored the therapeutic potential of LXA4 and a synthetic LX analog
      (Benzo-LXA4) to modulate diabetic complications in the streptozotocin-induced
      diabetic ApoE-/- mouse and in human carotid plaque tissue ex vivo. The
      development of diabetes-induced aortic plaques and inflammatory responses of
      aortic tissue, including the expression of vcam-1, mcp-1, il-6, and il-1beta, was
      significantly attenuated by both LXA4 and Benzo-LXA4 in diabetic ApoE-/- mice.
      Importantly, in mice with established atherosclerosis, treatment with LXs for a 6
      week period, initiated 10 weeks after diabetes onset, led to a significant
      reduction in aortic arch plaque development (19.22 +/- 2.01% [diabetic]; 12.67 +/
      1.68% [diabetic + LXA4]; 13.19 +/- 1.97% [diabetic + Benzo-LXA4]). Secretome
      profiling of human carotid plaque explants treated with LXs indicated changes to
      proinflammatory cytokine release, including tumor necrosis factor-alpha and
      interleukin-1beta. LXs also inhibited platelet-derived growth factor-stimulated
      vascular smooth muscle cell proliferation and transmigration and endothelial cell
      inflammation. These data suggest that LXs may have therapeutic potential in the
      context of diabetes-associated vascular complications.

PMID- 30213824
TI  - Histone H3 Serine 10 Phosphorylation Facilitates Endothelial Activation in
      Diabetic Kidney Disease.
AB  - The posttranslational histone modifications that epigenetically affect gene
      transcription extend beyond conventionally studied methylation and acetylation
      patterns. By examining the means by which podocytes influence the glomerular
      endothelial phenotype, we identified a role for phosphorylation of histone H3 on
      serine residue 10 (phospho-histone H3Ser10) in mediating endothelial activation
      in diabetes. Culture media conditioned by podocytes exposed to high glucose
      caused glomerular endothelial vascular cell adhesion protein 1 (VCAM-1)
      upregulation and was enriched for the chemokine CCL2. A neutralizing anti-CCL2
      antibody prevented VCAM-1 upregulation in cultured glomerular endothelial cells,
      and knockout of the CCL2 receptor CCR2 diminished glomerular VCAM-1 upregulation
      in diabetic mice. CCL2/CCR2 signaling induced glomerular endothelial VCAM-1
      upregulation through a pathway regulated by p38 mitogen-activated protein kinase,
      mitogen- and stress-activated protein kinases 1/2 (MSK1/2), and phosphorylation
      of H3Ser10, whereas MSK1/2 inhibition decreased H3Ser10 phosphorylation at the
      VCAM1 promoter. Finally, increased phospho-histone H3Ser10 levels were observed
      in the kidneys of diabetic endothelial nitric oxide synthase knockout mice and in
      the glomeruli of humans with diabetic kidney disease. These findings demonstrate
      the influence that histone protein phosphorylation may have on gene activation in
      diabetic kidney disease. Histone protein phosphorylation should be borne in mind
      when considering epigenetic targets amenable to therapeutic manipulation in
      diabetes.

PMID- 30213825
TI  - CETP Inhibition Improves HDL Function but Leads to Fatty Liver and Insulin
      Resistance in CETP-Expressing Transgenic Mice on a High-Fat Diet.
AB  - In clinical trials, inhibition of cholesteryl ester transfer protein (CETP)
      raises HDL cholesterol levels but does not robustly improve cardiovascular
      outcomes. Approximately two-thirds of trial participants are obese. Lower plasma
      CETP activity is associated with increased cardiovascular risk in human studies,
      and protective aspects of CETP have been observed in mice fed a high-fat diet
      (HFD) with regard to metabolic outcomes. To define whether CETP inhibition has
      different effects depending on the presence of obesity, we performed short-term
      anacetrapib treatment in chow- and HFD-fed CETP transgenic mice. Anacetrapib
      raised HDL cholesterol and improved aspects of HDL functionality, including
      reverse cholesterol transport, and HDL's antioxidative capacity in HFD-fed mice
      was better than in chow-fed mice. Anacetrapib worsened the anti-inflammatory
      capacity of HDL in HFD-fed mice. The HDL proteome was markedly different with
      anacetrapib treatment in HFD- versus chow-fed mice. Despite benefits on HDL,
      anacetrapib led to liver triglyceride accumulation and insulin resistance in HFD
      fed mice. Overall, our results support a physiologic importance of CETP in
      protecting from fatty liver and demonstrate context selectivity of CETP
      inhibition that might be important in obese subjects.

PMID- 30213827
TI  - JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently mutated in T-cell/histiocyte
      rich large B-cell lymphoma.
AB  - T-cell/histiocyte-rich large B-cell lymphoma is a rare aggressive lymphoma
      showing histopathological overlap with nodular lymphocyte predominant Hodgkin
      lymphoma. Despite differences in tumor microenvironment and clinical behavior,
      the tumor cells of both entities show remarkable similarities, suggesting that
      both lymphomas might represent a spectrum of the same disease. To address this
      issue, we investigated if these entities share mutations. Ultra-deep targeted
      resequencing of 6 typical and 11 histopathological variants of nodular lymphocyte
      predominant Hodgkin lymphoma, and 9 T-cell/histiocyte-rich large B-cell lymphoma
      cases revealed that genes recurrently mutated in nodular lymphocyte predominant
      Hodgkin lymphoma are affected by mutations at similar frequencies in T
      cell/histiocyte-rich large B-cell lymphoma. The most recurrently mutated genes
      were JUNB, DUSP2, SGK1, SOCS1 and CREBBP, which harbored mutations more
      frequently in T-cell/histiocyte-rich large B-cell lymphoma and the
      histopathological variants of nodular lymphocyte predominant Hodgkin lymphoma
      compared to its typical form. Mutations in JUNB, DUSP2, SGK1 and SOCS1 were
      highly enriched for somatic hypermutation hotspot sites, suggesting an important
      role of aberrant somatic hypermutation in the generation of these somatic
      mutations and thus in the pathogenesis of both lymphoma entities. Mutations in
      JUNB are generally rarely observed in malignant lymphomas and thus are relatively
      specific for nodular lymphocyte predominant Hodgkin lymphoma and T
      cell/histiocyte-rich large B-cell lymphoma at such high frequencies (5/17 and 5/9
      cases with JUNB mutations, respectively). Taken together, the present study
      further supports a close relationship of T-cell/histiocyte-rich large B-cell
      lymphoma and nodular lymphocyte predominant Hodgkin lymphoma by showing that they
      share highly recurrent genetic lesions.

PMID- 30213828
TI  - TLR7 ligand R848 prevents mouse graft-versus-host disease and cooperates with
      anti-IL-27 antibody for maximal protection and Treg upregulation.
AB  - In spite of considerable therapeutic progress, acute graft-versus-host disease
      still limits allogeneic hematopoietic cell transplantation. We recently reported
      that mouse infection with nidovirus lactate dehydrogenase elevating virus impairs
      disease in non-conditioned B6D2F1 recipients of parental B6 spleen cells. As this
      virus activates TLR7, we tested pharmacologic TLR7 ligand R848 in this model and
      observed complete survival if donor and recipients were treated before
      transplantation. Mixed lymphocyte culture performed 48 h after R848-treatment of
      normal mice demonstrated that both T cell allo-responsiveness and antigen
      presentation by CD11b+ and CD8alpha+ dendritic cells were inhibited. These
      inhibitions were dependent on IFNAR-1 signaling. In the B6 to B6D2F1
      transplantation model, R848 decelerated, but did not abrogate, donor T cell
      implantation and activation. However, it decreased IFNgamma, TNFalpha and IL-27
      while upregulating active TGF-beta1 plasma levels. In addition, donor and
      recipient Foxp3+ regulatory T cell numbers were increased in recipient mice and
      their elimination compromised disease prevention. R848 also strongly improved
      survival of lethally irradiated BALB/c recipients of B6 hematopoietic cells and
      this also correlated with an upregulation of CD4 and CD8 Foxp3+ regulatory T
      cells that could be further increased by IL-27 inhibition. The anti-IL-27p28
      monoclonal antibody and R848 combination also showed strong synergy in preventing
      disease in the B6 to B6D2F1 transplantation model when recipients were
      sublethally irradiated and this also correlated with Treg upregulation. We
      conclude that R848 modulates multiple aspects of graft-versus-host disease and
      offers potential for safe allogeneic bone marrow transplantation that can be
      further optimized by IL-27 inhibition.

PMID- 30213826
TI  - Effect of Chronic Hyperglycemia on Glucose Metabolism in Subjects With Normal
      Glucose Tolerance.
AB  - Chronic hyperglycemia causes insulin resistance, but the inheritability of
      glucotoxicity and the underlying mechanisms are unclear. We examined the effect
      of 3 days of hyperglycemia on glucose disposal, enzyme activities, insulin
      signaling, and protein O-GlcNAcylation in skeletal muscle of individuals without
      (FH-) or with (FH+) family history of type 2 diabetes. Twenty-five subjects with
      normal glucose tolerance received a [3-3H]glucose euglycemic insulin clamp,
      indirect calorimetry, and vastus-lateralis biopsies before and after 3 days of
      saline (n = 5) or glucose (n = 10 FH- and 10 FH+) infusion to raise plasma
      glucose by ~45 mg/dL. At baseline, FH+ had lower insulin-stimulated glucose
      oxidation and total glucose disposal (TGD) but similar nonoxidative glucose
      disposal and basal endogenous glucose production (bEGP) compared with FH- After 3
      days of glucose infusion, bEGP and glucose oxidation were markedly increased,
      whereas nonoxidative glucose disposal and TGD were lower versus baseline, with no
      differences between FH- and FH+ subjects. Hyperglycemia doubled skeletal muscle
      glycogen content and impaired activation of glycogen synthase (GS), pyruvate
      dehydrogenase, and Akt, but protein O-GlcNAcylation was unchanged. Insulin
      resistance develops to a similar extent in FH- and FH+ subjects after chronic
      hyperglycemia, without increased protein O-GlcNAcylation. Decreased nonoxidative
      glucose disposal due to impaired GS activation appears to be the primary deficit
      in skeletal muscle glucotoxicity.

PMID- 30213829
TI  - Long non-coding RNA NEAT1 shows high expression unrelated to molecular features
      and clinical outcome in multiple myeloma.

PMID- 30213830
TI  - Somatic reversion events point towards RPL4 as a novel disease gene in a
      condition resembling Diamond-Blackfan Anemia.

PMID- 30213831
TI  - Prevalence and management of iron overload in pyruvate kinase deficiency: report
      from the Pyruvate Kinase Deficiency Natural History Study.

PMID- 30213832
TI  - Long-term follow-up of Pediatric Philadelphia Positive Acute Lymphoblastic
      Leukemia treated with the EsPhALL2004 study: high white blood cell count at
      diagnosis is the strongest prognostic factor.

PMID- 30213833
TI  - Exposure to non-inherited maternal antigens by breastfeeding affects antibody
      responsiveness.
AB  - The observation, by Ray Owen and colleagues in 1954, that D-negative women were
      less likely to form anti-D antibodies against their D-positive fetus if their
      mother possessed the D-antigen, was not found in all later studies. We
      hypothesized that breastfeeding, received by the mother, may affect her immunity
      against non-inherited maternal red blood cell antigens. We studied a cohort of
      125 grandmother-mother-child combinations, from a follow-up study of mothers
      after intrauterine transfusion of the fetus for alloimmune hemolytic disease. For
      mismatched red blood cell antigens the mother was exposed to, whether or not
      antibodies were formed, we determined whether her mother, the grandmother,
      carried these antigens. The duration for which the mothers were breastfed was
      estimated by a questionnaire. Using multivariate logistic regression analyses,
      the interaction term (non-inherited maternal antigen exposure by categorized
      breastfeeding period) showed that a longer breastfeeding period was associated
      with decreased alloimmunization against non-inherited maternal antigens (adjusted
      odds ratio 0.66; 95% confidence interval 0.48-0.93). Sensitivity analysis with
      dichotomized (shorter versus longer) breastfeeding periods showed that this lower
      risk was reached after two months (aOR 0.22; 95% CI 0.07-0.71) and longer
      duration of breastfeeding did not seem to provide additional protection. These
      data suggest that oral neonatal exposure to non-inherited maternal red blood cell
      antigens through breastfeeding for at least two months diminish the risk of
      alloimmunization against these antigens when encountered later in life.

PMID- 30213834
TI  - Treatment outcomes and prognostic factors of adult patients with non-malignancy
      associated secondary hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis is an overwhelming systemic inflammatory
      process that is life-threatening if not treated appropriately. We analyzed
      prognostic factors of secondary hemophagocytic lymphohistiocytosis excluding
      malignancy. In this retrospective study, we analyzed 126 adult cases between 2001
      and 2017. Treatment was based on dexamethasone with or without etoposide and
      cyclosporine. Patients who achieved complete response at 4 weeks were defined as
      early-stable responders, those who failed to achieve complete response but showed
      continuous improvement until 8 weeks as late responders, those whose conditions
      waxed and waned until 8 weeks as unstable responders. Patients with
      hemophagocytic lymphohistiocytosis caused by Epstein-Barr virus experienced worse
      5-year overall survival compared to autoimmune disease, other infections, and
      unknown causes (25.1% vs. 82.4%, 78.7%, 55.5%, p<0.001). We observed that overall
      response rate at 4 weeks was similar, but decreased at 8 weeks in the Epstein
      Barr virus subgroup from 75.5% to 51.0%, and finally decreased to 30.6%.
      Multivariate analysis revealed that 8-week treatment response was the most
      relevant factor for overall survival. Excluding 8-week response, Epstein-Barr
      virus, old age, hyperferritinemia, and thrombocytopenia were associated with poor
      survival. We established a prognostic model with the parameters: low-risk (score
      0-1), intermediate-risk (score 2), and high-risk (score>=3). These groups had 5
      year overall survival of 92.1%, 36.8%, and 18.0%, respectively (p<0.001). We
      found that 8-week treatment response was a good predictive factor for overall
      survival, and that Epstein-Barr virus, old age, thrombocytopenia, and
      hyperferritinemia were associated with poor survival outcomes. Physicians should
      take care to identify high-risk patients for appropriate treatment strategies.

PMID- 30213836
TI  - CHIPing out PPM1D-mutant hematopoiesis.

PMID- 30213837
TI  - The incomparable platelet: holy alveoli!

PMID- 30213835
TI  - Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian
      Cancer Organoids.
AB  - Based on genomic analysis, 50% of high-grade serous ovarian cancers (HGSC) are
      predicted to have DNA repair defects. Whether this substantial subset of HGSCs
      actually have functional repair defects remains unknown. Here, we devise a
      platform for functional profiling of DNA repair in short-term patient-derived
      HGSC organoids. We tested 33 organoid cultures derived from 22 patients with HGSC
      for defects in homologous recombination (HR) and replication fork protection.
      Regardless of DNA repair gene mutational status, a functional defect in HR in the
      organoids correlated with PARP inhibitor sensitivity. A functional defect in
      replication fork protection correlated with carboplatin and CHK1 and ATR
      inhibitor sensitivity. Our results indicate that a combination of genomic
      analysis and functional testing of organoids allows for the identification of
      targetable DNA damage repair defects. Larger numbers of patient-derived organoids
      must be analyzed to determine whether these assays can reproducibly predict
      patient response in the clinic.Significance: Patient-derived ovarian tumor
      organoids grow rapidly and match the tumors from which they are derived, both
      genetically and functionally. These organoids can be used for DNA repair
      profiling and therapeutic sensitivity testing and provide a rapid means of
      assessing targetable defects in the parent tumor, offering more suitable
      treatment options. Cancer Discov; 8(11); 1404-21. (c)2018 AACR. This article is
      highlighted in the In This Issue feature, p. 1333.

PMID- 30213838
TI  - Platelet metabolism meets thrombosis.

PMID- 30213839
TI  - Rhesus pieces: genotype matching of RBCs.

PMID- 30213840
TI  - Hairy cell leukemia in a child?!

PMID- 30213841
TI  - An Abeta42 variant that inhibits intra- and extracellular amyloid aggregation and
      enhances cell viability.
AB  - Aggregation and accumulation of the 42-residue amyloid beta peptide (Abeta42) in
      the extracellular matrix and within neuronal cells is considered a major cause of
      neuronal cell cytotoxicity and death in Alzheimer's disease (AD) patients.
      Therefore, molecules that bind to Abeta42 and prevent its aggregation are
      therapeutically promising as AD treatment. Here, we show that a non-self
      aggregating Abeta42 variant carrying two surface mutations, F19S and L34P
      (Abeta42DM), inhibits wild-type Abeta42 aggregation and significantly reduces
      Abeta42-mediated cell cytotoxicity. In addition, Abeta42DM inhibits the uptake
      and internalization of extracellularly added pre-formed Abeta42 aggregates into
      cells. This was the case in both neuronal and non-neuronal cells co-expressing
      Abeta42 and Abeta42DM or following pre-treatment of cells with extracellular
      soluble forms of the two peptides, even at high Abeta42 to Abeta42DM molar
      ratios. In cells, Abeta42DM associates with Abeta42, while in vitro, the two
      soluble recombinant peptides exhibit nano-molar binding affinity. Importantly,
      Abeta42DM potently suppresses Abeta42 amyloid aggregation in vitro, as
      demonstrated by thioflavin T fluorescence and transmission electron microscopy
      for detecting amyloid fibrils. Overall, we present a new approach for inhibiting
      Abeta42 fibril formation both within and outside cells. Accordingly, Abeta42DM
      should be evaluated in vivo for potential use as a therapeutic lead for treating
      AD.

PMID- 30213842
TI  - Medical Marijuana for Minors May Be Considered Child Abuse.
AB  - The Food and Drug Administration categorizes marijuana (cannabis) as a Schedule I
      drug, meaning that it has no currently accepted medical use, a high potential for
      abuse, and no good data on safety. Other Schedule I drugs are heroin, lysergic
      acid diethylamide, peyote, methaqualone, and 3,4-methylenedioxymethamphetamine
      ("ecstasy"). The authors of some studies have shown that marijuana can reduce
      nausea and vomiting from chemotherapy, can improve food intake in patients with
      HIV, can reduce neuropathic pain, and may slow the growth of cancer cells. In
      many states, marijuana use is illegal. No state has approved its use for
      children. What, then, should doctors do if they become aware that parents are
      using marijuana to treat medical conditions in their children? What if the
      children have adverse reactions to the marijuana? In this Ethics Rounds, we
      present such a case and ask experts in child protection and child abuse to
      discuss the appropriate response.

PMID- 30213843
TI  - Eye Findings in Infants With Suspected or Confirmed Antenatal Zika Virus
      Exposure.
AB  - : : media-1vid110.1542/5804915134001PEDS-VA_2018-1104Video Abstract OBJECTIVES:
      To characterize ophthalmic manifestations of confirmed or suspected antenatal
      Zika virus (ZIKV) exposure. METHODS: Infants with antenatal ZIKV exposure were
      referred for evaluation during the 2015-2016 Rio de Janeiro outbreak. Mothers
      with symptomatic ZIKV infection during pregnancy and/or infants with microcephaly
      or other findings that were suggestive of suspected antenatal exposure were
      tested with reverse transcriptase polymerase chain reaction (RT-PCR). Complete
      eye examinations were performed by pediatric ophthalmologists between January
      2016 and February 2017. The main outcome measure was eye abnormalities in RT-PCR
      positive and suspected (ie, not tested or RT-PCR-negative) antenatal ZIKV cases.
      RESULTS: Of 224 infants, 189 had RT-PCR testing performed. Of 189 patients, 156
      had positive RT-PCR results in their blood, urine, and/or placenta. Of 224
      infants, 90 had central nervous system (CNS) abnormalities, including
      microcephaly (62 infants). Eye abnormalities were present in 57 of 224 (25.4%)
      infants. Optic nerve (44 of 57; 77.2%) and retina abnormalities (37 of 57; 64.9%)
      were the most common. The group with suspected ZIKV infection (68 infants) had
      proportionally more eye (36.8% vs 20.5%; P = .022) and CNS abnormalities (68.3%
      vs 28.1%; P = .008), likely because of referral patterns. Eye abnormalities
      consistent with ZIKV infection were clinically comparable in both RT-PCR-positive
      and unconfirmed groups, including 4 RT-PCR-positive infants of 5 without any CNS
      abnormalities. CONCLUSIONS: Similar eye manifestations were identified regardless
      of laboratory confirmation. Well-appearing infants were also found to have eye
      abnormalities. Therefore, all infants born after ZIKV outbreaks should be
      universally screened for eye abnormalities.

PMID- 30213844
TI  - Proteomic profiling of mouse epididymosomes reveals their contributions to post
      testicular sperm maturation.
AB  - The functional maturation of spermatozoa that is necessary to achieve
      fertilization occurs as they transit through the epididymis, a highly specialized
      region of the male reproductive tract. A defining feature of this maturation
      process is that it occurs in the complete absence of nuclear gene transcription
      or de novo protein translation in the spermatozoa. Rather, it is driven by
      sequential interactions between spermatozoa and the complex external milieu in
      which they are bathed within lumen of the epididymal tubule. A feature of this
      dynamic microenvironment are epididymosomes, small membrane encapsulated vesicles
      that are secreted from the epididymal soma. Herein, we report comparative
      proteomic profiling of epididymosomes isolated from different segments of the
      mouse epididymis using multiplexed tandem mass tag (TMT) based quantification
      coupled with high resolution LC-MS/MS. A total of 1640 epididymosome proteins
      were identified and quantified via this proteomic method. Notably, this analysis
      revealed pronounced segment-to-segment variation in the encapsulated
      epididymosome proteome. Thus, 146 proteins were identified as being
      differentially accumulated between caput and corpus epididymosomes, and a further
      344 were differentially accumulated between corpus and cauda epididymosomes (i.e.
      fold change of  -1.5 or  1.5; P < 0.05). Application of gene ontology annotation
      revealed a substantial portion of the epididymosome proteins mapped to the
      cellular component of extracellular exosome and to the biological processes of
      transport, oxidation-reduction, and metabolism. Additional annotation of the
      subset of epididymosome proteins that have not previously been identified in
      exosomes revealed enrichment of categories associated with the acquisition of
      sperm function (e.g. fertilization and binding to the zona pellucida). In tandem
      with our demonstration that epididymosomes are able to convey protein cargo to
      the head of maturing spermatozoa, these data emphasize the fundamental importance
      of epididymosomes as key elements of the epididymal microenvironment responsible
      for coordinating post-testicular sperm maturation.

PMID- 30213845
TI  - Nuclear Medicine Procedures Do Not Pose Cancer Risks in Women-Unappreciated or
      Otherwise.

PMID- 30213847
TI  - Optimizing Longitudinal Amyloid-beta PET Measurement: The Challenges of Intensity
      Normalization.

PMID- 30213846
TI  - Evaluation of a novel PET radioligand to image O-GlcNAcase in brain and periphery
      of rhesus monkey and knock-out mouse.
AB  - Accumulation of hyper-phosphorylated tau, a microtubule-associated protein, plays
      an important role in the progression of Alzheimer's disease (AD). Animal studies
      suggest that one strategy for treating AD and related tauopathies may be
      inhibition of O-GlcNAcase (OGA), which may subsequently decrease pathological tau
      phosphorylation Here, we report the pharmacokinetics of a novel positron emission
      tomography (PET) radioligand, 18F-LSN3316612, which binds with high affinity and
      selectivity to OGA. Methods: PET imaging was performed in rhesus monkeys at
      baseline and after administration of either thiamet G, a potent OGA inhibitor, or
      nonradioactive LSN3316612. The density of the enzyme was calculated as
      distribution volume (VT) using a two-tissue compartment model and serial
      concentrations of parent radioligand in arterial plasma. The radiation burden for
      future studies was calculated based on whole-body imaging of monkeys. Oga?Br, a
      mouse brain-specific knockout of Oga, was also scanned to assess the specificity
      of the radioligand for its target enzyme. Results: Uptake of radioactivity in
      monkey brain was high (~5 SUV) and followed by slow washout. The highest uptake
      was in the amygdala, followed by striatum and hippocampus. Pretreatment with
      thiamet G or nonradioactive LSN3316612 reduced brain uptake to a low and uniform
      concentration in all regions, corresponding to an approximately 90% decrease in
      VT. Whole-body imaging in rhesus monkeys showed high uptake in kidney, spleen,
      liver, and testes. In Oga?Br mice, brain uptake of 18F-LSN3316612 was reduced by
      82% compared to control mice. Peripheral organs were unaffected in Oga?Br mice,
      consistent with loss of OGA expression exclusively in the brain. The effective
      dose of 18F- LSN3316612 in humans was calculated to be 22 uSv/MBq, which is
      typical for 18F-labeled radioligands. Conclusion: These results show that 18F
      LSN3316612 is an excellent radioligand for imaging and quantifying OGA in rhesus
      monkeys and mice. Based on these data, 18F-LSN3316612 merits evaluation in
      humans.

PMID- 30213848
TI  - Three-hour delayed imaging improves assessment of coronary 18F-sodium fluoride
      PET.
AB  - Coronary 18F-sodium fluoride (18F-NaF) PET imaging identifies ruptured plaques in
      patients with recent myocardial infarction and localizes to atherosclerotic
      lesions with active calcification. Most studies to date performed the PET
      acquisition 1-hour (1h) post-injection. Although qualitative and semi
      quantitative analysis is feasible with 1h images, often residual blood pool
      activity makes it difficult to discriminate plaques with 18F-NaF uptake from
      noise. We aimed to assess whether delayed 3-hour (3h) post-injection PET scan
      improves image quality and uptake measurements. Methods: Twenty patients (67+/
      7years old, 55% male) with stable coronary artery disease underwent coronary CT
      angiography and PET/CT both 1 h and 3 h after the injection of 266.2+/-13.3 MBq
      of 18F-NaF. We compared the visual pattern of coronary uptake, maximal background
      (blood pool) activity, noise, standard uptake values (SUVmax), corrected SUV
      (cSUVmax) and target to background (TBR) measurements in lesions defined by CTA
      on 1h vs 3h post injection 18F-NaF PET. Results: On 1h PET 26 CTA lesions with
      18F-NaF PET uptake were identified in 12 (60%) patients. On 3h PET we detected
      18F-NaF PET uptake in 7 lesions which were not identified on the 1h PET. The
      median cSUVmax and TBR values of these lesions were 0.48 [interquartile range
      (IQR) 0.44-0.51] and 1.45 [IQR, 1.39-1.52] compared to -0.01 [IQR, -0.03-0.001]
      and 0.95 [IQR, 0.90-0.98] on 1h PET, both p<0.001. Across the entire cohort 3h
      PET SUVmax values were similar to 1h PET measurements 1.63 [IQR, 1.37-1.98] vs.
      1.55 [IQR, 1.43-1.89], P = 0.30 and the background activity was lower 0.71 [IQR,
      0.65-0.81] vs. 1.24 [IQR, 1.05-1.31], p<0.001. On 3h PET, the TBR values, cSUVmax
      and the noise were significantly higher (2.30 [IQR, 1.70-2.68] vs 1.28 [IQR, 0.98
      1.56], p<0.001; 0.38 [IQR, 0.27-0.70] vs 0.90 [IQR, 0.64-1.17], p<0.001 and 0.10
      [IQR, 0.09-0.12] vs. 0.07 [IQR, 0.06-0.09], P = 0.02). The median cSUVmax and TBR
      values increased by 92% (range: 33-225%) and 80% (range: 20-177%). Conclusion:
      Blood-pool activity decreases on delayed imaging facilitating the assessment of
      18F-NaF uptake in coronary plaques. The median target to background ratios
      increase by 80% leading to the detection of more plaques with significant uptake
      compared to the standard 1h protocol. A greater than a 1h delay may improve the
      detection of 18F-NaF uptake in coronary artery plaques.

PMID- 30213849
TI  - Affibody-based PET imaging to guide EGFR-targeted cancer therapy in head and neck
      squamous cell cancer models.
AB  - In head and neck squamous cell carcinoma (HNSCC), the human epidermal growth
      factor receptor 1 (EGFR) is the dominant signaling molecule among all members of
      the family. So far, cetuximab is the only approved anti-EGFR mAb used for the
      treatment of HNSCC, but despite the benefits of adding it to standard treatment
      regimens, attempts to define a predictive biomarker to stratify patients for
      cetuximab treatment have been unsuccessful. We hypothesized that imaging with
      EGFR-specific radioligands may facilitate non-invasive measurement of EGFR
      expression across the entire tumor burden and also allow for dynamic monitoring
      of cetuximab-mediated changes in receptor expression. Methods: EGFR-specific
      Affibody molecule (ZEGFR:03115) was radiolabeled with zirconium-89 (89Zr) and
      fluorine-18 (18F). The radioligands were characterized in vitro and in mice
      bearing subcutaneous tumors with varying levels of EGFR expression. The protein
      dose for imaging studies was assessed by injecting 89Zr-DFO-ZEGFR:03115 (2.4-3.6
      MBq, 2 ug) either together with or 30 mins after increasing amounts of unlabeled
      ZEGFR:03115 (1, 5, 10, 15 and 20 ug). PET images were acquired at 3, 24 and 48 h
      post-injection and the image quantification data were correlated with the
      biodistribution results. The EGFR expression and biodistribution of the tracer
      were assessed ex vivo by immunohistochemistry, Western blot and autoradiography.
      To downregulate the EGFR level, treatment with cetuximab was performed and 18F
      AlF-NOTA-ZEGFR:03115 (12 ug, 1.5-2 MBq/mouse) used to monitor receptor changes.
      Results: In vivo studies demonstrated that co-injecting 10 ug of non-labeled
      molecules with 89Zr-DFO-ZEGFR:03115 allows for clear tumor visualization 3 h post
      injection. The radioconjugate tumor accumulation was EGFR-specific and PET
      imaging data showed a clear differentiation between xenografts with varying EGFR
      expression levels. A strong correlation was observed between PET analysis, ex
      vivo estimates of tracer concentration and receptor expression in tumor tissues.
      Additionally, 18F-AlF-NOTA-ZEGFR:03115 could measure receptor downregulation in
      response to EGFR inhibition. Conclusion: ZEGFR03115-based radioconjugates can
      assess different levels of EGFR level in vivo and measure receptor expression
      changes in response to cetuximab, indicating a potential for assessment of
      adequate treatment dosing with anti-EGFR antibodies.

PMID- 30213850
TI  - Neural-inspired sensors enable sparse, efficient classification of spatiotemporal
      data.
AB  - Sparse sensor placement is a central challenge in the efficient characterization
      of complex systems when the cost of acquiring and processing data is high.
      Leading sparse sensing methods typically exploit either spatial or temporal
      correlations, but rarely both. This work introduces a sparse sensor optimization
      that is designed to leverage the rich spatiotemporal coherence exhibited by many
      systems. Our approach is inspired by the remarkable performance of flying
      insects, which use a few embedded strain-sensitive neurons to achieve rapid and
      robust flight control despite large gust disturbances. Specifically, we identify
      neural-inspired sensors at a few key locations on a flapping wing that are able
      to detect body rotation. This task is particularly challenging as the rotational
      twisting mode is three orders of magnitude smaller than the flapping modes. We
      show that nonlinear filtering in time, built to mimic strain-sensitive neurons,
      is essential to detect rotation, whereas instantaneous measurements fail.
      Optimized sparse sensor placement results in efficient classification with
      approximately 10 sensors, achieving the same accuracy and noise robustness as
      full measurements consisting of hundreds of sensors. Sparse sensing with neural
      inspired encoding establishes an alternative paradigm in hyperefficient, embodied
      sensing of spatiotemporal data and sheds light on principles of biological
      sensing for agile flight control.

PMID- 30213851
TI  - Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I
      molecules.
AB  - The repertoire of peptides displayed at the cell surface by MHC I molecules is
      shaped by two intracellular peptide editors, tapasin and TAPBPR. While cell-free
      assays have proven extremely useful in identifying the function of both of these
      proteins, here we explored whether a more physiological system could be developed
      to assess TAPBPR-mediated peptide editing on MHC I. We reveal that membrane
      associated TAPBPR targeted to the plasma membrane retains its ability to function
      as a peptide editor and efficiently catalyzes peptide exchange on surface
      expressed MHC I molecules. Additionally, we show that soluble TAPBPR, consisting
      of the luminal domain alone, added to intact cells, also functions as an
      effective peptide editor on surface MHC I molecules. Thus, we have established
      two systems in which TAPBPR-mediated peptide exchange on MHC class I can be
      interrogated. Furthermore, we could use both plasma membrane-targeted and
      exogenous soluble TAPBPR to display immunogenic peptides on surface MHC I
      molecules and consequently induce T cell receptor engagement, IFN-gamma
      secretion, and T cell-mediated killing of target cells. Thus, we have developed
      an efficient way to by-pass the natural antigen presentation pathway of cells and
      load immunogenic peptides of choice onto cells. Our findings highlight a
      potential therapeutic use for TAPBPR in increasing the immunogenicity of tumors
      in the future.

PMID- 30213852
TI  - Parp3 promotes long-range end joining in murine cells.
AB  - Chromosomal rearrangements, including translocations, are early and essential
      events in the formation of many tumors. Previous studies that defined the genetic
      requirements for rearrangement formation have identified differences between
      murine and human cells, most notably in the role of classic and alternative
      nonhomologous end-joining (NHEJ) factors. We reported that poly(ADP)ribose
      polymerase 3 (PARP3) promotes chromosomal rearrangements induced by endonucleases
      in multiple human cell types. We show here that in contrast to classic (c-NHEJ)
      factors, Parp3 also promotes rearrangements in murine cells, including
      translocations in murine embryonic stem cells (mESCs), class-switch recombination
      in primary B cells, and inversions in tail fibroblasts that generate Eml4-Alk
      fusions. In mESCs, Parp3-deficient cells had shorter deletion lengths at
      translocation junctions. This was corroborated using next-generation sequencing
      of Eml4-Alk junctions in tail fibroblasts and is consistent with a role for Parp3
      in promoting the processing of DNA double-strand breaks. We confirmed a previous
      report that Parp1 also promotes rearrangement formation. In contrast with Parp3,
      rearrangement junctions in the absence of Parp1 had longer deletion lengths,
      suggesting that Parp1 may suppress double-strand break processing. Together,
      these data indicate that Parp3 and Parp1 promote rearrangements with distinct
      phenotypes.

PMID- 30213854
TI  - Robust Genome Editing with Short Single-Stranded and Long, Partially Single
      Stranded DNA Donors in Caenorhabditis elegans.
AB  - CRISPR-based genome editing using ribonucleoprotein complexes and synthetic
      single-stranded oligodeoxynucleotide (ssODN) donors can be highly effective.
      However, reproducibility can vary, and precise, targeted integration of longer
      constructs-such as green fluorescent protein tags remains challenging in many
      systems. Here, we describe a streamlined and optimized editing protocol for the
      nematode Caenorhabditis elegans We demonstrate its efficacy, flexibility, and
      cost-effectiveness by affinity-tagging 14 Argonaute proteins in C. elegans using
      ssODN donors. In addition, we describe a novel PCR-based, partially single
      stranded, "hybrid" donor design that yields high efficiency editing with large
      (kilobase-scale) constructs. We use these hybrid donors to introduce fluorescent
      protein tags into multiple loci, achieving editing efficiencies that approach
      those previously obtained only with much shorter ssODN donors. The principals and
      strategies described here are likely to translate to other systems, and should
      allow researchers to reproducibly and efficiently obtain both long and short
      precision genome edits.

PMID- 30213856
TI  - Inhibitors and chemical probes for molecular chaperone networks.
AB  - The molecular chaperones are central mediators of protein homeostasis. In that
      role, they engage in widespread protein-protein interactions (PPIs) with each
      other and with their "client" proteins. Together, these PPIs form the backbone of
      a network that ensures proper vigilance over the processes of protein folding,
      trafficking, quality control and degradation. The core chaperones, such as the
      heat shock proteins Hsp60, Hsp70 and Hsp90, are widely expressed in most tissues,
      yet there is growing evidence that the PPIs among them may be re-wired in disease
      conditions. This possibility suggests that these PPIs, and perhaps not the
      individual chaperones themselves, could be compelling drug targets. Indeed,
      recent efforts have yielded small molecules that inhibit (or promote) a subset of
      inter-chaperone PPIs. These chemical probes are being used to study chaperone
      networks in a range of models and the successes with these approaches have
      inspired a community-wide objective to produce inhibitors for a broader set of
      targets. In this review, we discuss progress towards that goal and point out some
      of the challenges ahead.

PMID- 30213853
TI  - Developmental stage-specific proliferation and retinoblastoma genesis in RB
      deficient human but not mouse cone precursors.
AB  - Most retinoblastomas initiate in response to the inactivation of the RB1 gene and
      loss of functional RB protein. The tumors may form with few additional genomic
      changes and develop after a premalignant retinoma phase. Despite this seemingly
      straightforward etiology, mouse models have not recapitulated the genetic,
      cellular, and stage-specific features of human retinoblastoma genesis. For
      example, whereas human retinoblastomas appear to derive from cone photoreceptor
      precursors, current mouse models develop tumors that derive from other retinal
      cell types. To investigate the basis of the human cone-specific oncogenesis, we
      compared developmental stage-specific cone precursor responses to RB loss in
      human and murine retina cultures and in cone-specific Rb1-knockout mice. We
      report that RB-depleted maturing (ARR3+) but not immature (ARR3-) human cone
      precursors enter the cell cycle, proliferate, and form retinoblastoma-like
      lesions with Flexner-Wintersteiner rosettes, then form low or nonproliferative
      premalignant retinoma-like lesions with fleurettes and p16INK4A and p130
      expression, and finally form highly proliferative retinoblastoma-like masses. In
      contrast, in murine retina, only RB-depleted immature (Arr3-) cone precursors
      entered the cell cycle, and they failed to progress from S to M phase. Moreover,
      whereas intrinsically highly expressed MDM2 and MYCN contribute to RB-depleted
      maturing (ARR3+) human cone precursor proliferation, ectopic MDM2 and Mycn
      promoted only immature (Arr3-) murine cone precursor cell-cycle entry. These
      findings demonstrate that developmental stage-specific as well as species- and
      cell type-specific features sensitize to RB1 inactivation and reveal the human
      cone precursors' capacity to model retinoblastoma initiation, proliferation,
      premalignant arrest, and tumor growth.

PMID- 30213855
TI  - A Robust Methodology for Assessing Differential Homeolog Contributions to the
      Transcriptomes of Allopolyploids.
AB  - Polyploidy has played a pivotal and recurring role in angiosperm evolution.
      Allotetraploids arise from hybridization between species and possess duplicated
      gene copies (homeologs) that serve redundant roles immediately after
      polyploidization. Although polyploidization is a major contributor to plant
      evolution, it remains poorly understood. We describe an analytical approach for
      assessing homeolog-specific expression that begins with de novo assembly of
      parental transcriptomes and effectively (i) reduces redundancy in de novo
      assemblies, (ii) identifies putative orthologs, (iii) isolates common regions
      between orthologs, and (iv) assesses homeolog-specific expression using a robust
      Bayesian Poisson-Gamma model to account for sequence bias when mapping polyploid
      reads back to parental references. Using this novel methodology, we examine
      differential homeolog contributions to the transcriptome in the recently formed
      allopolyploids Tragopogon mirus and T. miscellus (Compositae). Notably, we assess
      a larger Tragopogon gene set than previous studies of this system. Using
      carefully identified orthologous regions and filtering biased orthologs, we find
      in both allopolyploids largely balanced expression with no strong parental bias.
      These new methods can be used to examine homeolog expression in any
      tetrapolyploid system without requiring a reference genome.

PMID- 30213857
TI  - Apoptotic beta-cells induce macrophage reprogramming under diabetic conditions.
AB  - Type 2 diabetes mellitus (T2DM) occurs when insulin-producing pancreatic beta
      cells fail to secrete sufficient insulin to compensate for insulin resistance. As
      T2DM progresses, apoptotic beta-cells need to be removed by macrophages through
      efferocytosis that is anti-inflammatory by nature. Paradoxically, infiltrating
      macrophages are a main source of inflammatory cytokines that leads to T2DM. It is
      unclear how apoptotic beta-cells impact macrophage function. We show under
      diabetic conditions, phagocytosis of apoptotic beta-cells causes lysosomal
      permeabilization and generates reactive oxygen species that lead to inflammasome
      activation and cytokine secretion in macrophages. Efferocytosis-induced lipid
      accumulation transforms islet macrophages into foam cell-like outside the context
      of atherosclerosis. Our study suggests that whereas macrophages normally play a
      protective anti-inflammatory role, the increasing demand of clearing apoptotic
      cells may trigger them to undergo proinflammatory reprogramming as T2DM
      progresses. This shift in the balance between opposing macrophage inflammatory
      responses could contribute to chronic inflammation involved in metabolic
      diseases. Our study highlights the importance of preserving macrophage lysosomal
      function as a therapeutic intervention for diabetes progression.

PMID- 30213858
TI  - CatSper channels are regulated by protein kinase A.
AB  - Mammalian sperm must undergo capacitation as a preparation for entering into
      hyperactivated motility, undergoing the acrosome reaction, and acquiring
      fertilizing ability. One of the initial capacitation events occurs when sperm
      encounter an elevated HCO3 - concentration. This anion activates the atypical
      adenylyl cyclase Adcy10, increases intracellular cAMP, and stimulates protein
      kinase A (PKA). Moreover, an increase in intracellular Ca2+ concentration ([Ca2+]
      i ) is essential for sperm capacitation. Although a cross-talk between cAMP
      dependent pathways and Ca2+ clearly plays an essential role in sperm
      capacitation, the connection between these signaling events is incompletely
      understood. Here, using three different approaches, we found that CatSper, the
      main sperm Ca2+ channel characterized to date, is up-regulated by a cAMP
      dependent activation of PKA in mouse sperm. First, HCO3 - and the PKA-activating
      permeable compound 8-Br-cAMP induced an increase in [Ca2+] i , which was blocked
      by the PKA peptide inhibitor PKI, and H89, another PKA inhibitor, also abrogated
      the 8-Br-cAMP response. Second, HCO3 - increased the membrane depolarization
      induced upon divalent cation removal by promoting influx of monovalent cations
      through CatSper channels, which was inhibited by PKI, H89, and the CatSper
      blocker HC-056456. Third, electrophysiological patch clamp, whole-cell recordings
      revealed that CatSper activity is up-regulated by HCO3 - and by direct cAMP
      injection through the patch-clamp pipette. The activation by HCO3 - and cAMP was
      also blocked by PKI, H89, Rp-cAMPS, and HC-056456, and electrophysiological
      recordings in sperm from CatSper-KO mice confirmed CatSper's role in these
      activation modes. Our results strongly suggest that PKA-dependent phosphorylation
      regulates [Ca2+] i homeostasis by activating CatSper channel complexes.

PMID- 30213859
TI  - Discovery and characterization of conserved binding of eIF4E 1 (CBE1), a
      eukaryotic translation initiation factor 4E-binding plant protein.
AB  - In many eukaryotes, translation initiation is regulated by proteins that bind to
      the mRNA cap-binding protein eukaryotic translation initiation factor 4E (eIF4E).
      These proteins commonly prevent association of eIF4E with eIF4G or form
      repressive messenger ribonucleoproteins that exclude the translation machinery.
      Such gene-regulatory mechanisms in plants, and even the presence of eIF4E
      interacting proteins other than eIF4G (and the plant-specific isoform eIFiso4G,
      which binds eIFiso4E), are unknown. Here, we report the discovery of a plant
      specific protein, conserved binding of eIF4E 1 (CBE1). We found that CBE1 has an
      evolutionarily conserved eIF4E-binding motif in its N-terminal domain and binds
      eIF4E or eIFiso4E in vitro CBE1 thereby forms cap-binding complexes and is an
      eIF4E-dependent constituent of these complexes in vivo Of note, plant mutants
      lacking CBE1 exhibited dysregulation of cell cycle-related transcripts and
      accumulated higher levels of mRNAs encoding proteins involved in mitosis than did
      WT plants. Our findings indicate that CBE1 is a plant protein that can form mRNA
      cap-binding complexes having the potential for regulating gene expression.
      Because mammalian translation factors are known regulators of cell cycle
      progression, we propose that CBE1 may represent such first translation factor
      associated plant-specific cell cycle regulator.

PMID- 30213860
TI  - A versatile insulin analog with high potency for both insulin and insulin-like
      growth factor 1 receptors: Structural implications for receptor binding.
AB  - Insulin and insulin-like growth factor 1 (IGF-1) are closely related hormones
      involved in the regulation of metabolism and growth. They elicit their functions
      through activation of tyrosine kinase-type receptors: insulin receptors (IR-A and
      IR-B) and IGF-1 receptor (IGF-1R). Despite similarity in primary and three
      dimensional structures, insulin and IGF-1 bind the noncognate receptor with
      substantially reduced affinity. We prepared [d-HisB24, GlyB31, TyrB32]-insulin,
      which binds all three receptors with high affinity (251 or 338% binding affinity
      to IR-A respectively to IR-B relative to insulin and 12.4% binding affinity to
      IGF-1R relative to IGF-1). We prepared other modified insulins with the aim of
      explaining the versatility of [d-HisB24, GlyB31, TyrB32]-insulin. Through
      structural, activity, and kinetic studies of these insulin analogs, we concluded
      that the ability of [d-HisB24, GlyB31, TyrB32]-insulin to stimulate all three
      receptors is provided by structural changes caused by a reversed chirality at the
      B24 combined with the extension of the C terminus of the B chain by two extra
      residues. We assume that the structural changes allow the directing of the B
      chain C terminus to some extra interactions with the receptors. These unusual
      interactions lead to a decrease of dissociation rate from the IR and conversely
      enable easier association with IGF-1R. All of the structural changes were made at
      the hormones' Site 1, which is thought to interact with the Site 1 of the
      receptors. The results of the study suggest that merely modifications of Site 1
      of the hormone are sufficient to change the receptor specificity of insulin.

PMID- 30213861
TI  - WW domain-mediated regulation and activation of E3 ubiquitin ligase Suppressor of
      Deltex.
AB  - The Nedd4 family E3 ligases Itch and WWP1/2 play crucial roles in the regulation
      of cell cycle progression and apoptosis and are closely correlated with cancer
      development and metastasis. It has been recently shown that the ligase activities
      of Itch and WWP1/2 are tightly regulated, with the HECT domain sequestered
      intramolecularly by a linker region connecting WW2 and WW3. Here, we show that a
      similar autoinhibitory mechanism is utilized by the Drosophila ortholog of Itch
      and WWP1/2, Suppressor of Deltex (Su(dx)). We show that Su(dx) adopts an inactive
      steady state with the WW domain region interacting with the HECT domain. We
      demonstrate that both the linker and preceding WW2 are required for the efficient
      binding and regulation of Su(dx) HECT. Recruiting the multiple-PY motif
      containing adaptor dNdfip via WW domains relieves the inhibitory state of Su(dx)
      and leads to substrate (e.g. Notch) ubiquitination. Our study demonstrates an
      evolutionarily conservative mechanism governing the regulation and activation of
      some Nedd4 family E3 ligases. Our results also suggest a dual regulatory
      mechanism for specific Notch down-regulation via dNdfip-Su(dx)-mediated Notch
      ubiquitination.

PMID- 30213862
TI  - CD16a with oligomannose-type N-glycans is the only "low-affinity" Fc gamma
      receptor that binds the IgG crystallizable fragment with high affinity in vitro.
AB  - Fc gamma receptors (FcgammaRs) bind circulating IgG (IgG1) at the surface of
      leukocytes. Antibodies clustered at the surface of a targeted particle trigger a
      protective immune response through activating FcgammaRs. Three recent reports
      indicate that the composition of the asparagine-linked carbohydrate chains (N
      glycans) of FcgammaRIIIa/CD16a impacted IgG1-binding affinity. Here we determined
      how N-glycan composition affected the affinity of the "low-affinity" FcgammaRs
      for six homogeneous IgG1 Fc N-glycoforms (G0, G0F, G2, G2F, A2G2, and A2G2F).
      Surprisingly, CD16a with oligomannose N-glycans bound to IgG1 Fc (A2G2) with a KD
      = 1.0 +/- 0.1 nm This affinity represents a 51-fold increase over the affinity
      measured for CD16a with complex-type N-glycans (51 +/- 8 nm) and is comparable
      with the affinity of FcgammaRI/CD64, the sole "high-affinity" FcgammaR. CD16a N
      glycan composition accounted for increases in binding affinity for the other IgG1
      Fc glycoforms tested (10-50-fold). This remarkable sensitivity could only be
      eliminated by preventing glycosylation at Asn162 with an Asn-to-Gln mutation;
      mutations at the four other N-glycosylation sites preserved tighter binding in
      the Man5 glycoform. None of the other low-affinity FcgammaRs showed more than a
      3.1-fold increase upon modifying the receptor N-glycan composition, including
      CD16b, which differs from CD16a by only four amino acid residues. This result
      indicates that CD16a is unique among the low-affinity FcgammaRs, and modifying
      only the glycan composition of both the IgG1 Fc ligand and receptor provides a
      400-fold range in affinities.

PMID- 30213865
TI  - Knee pain in an athletic young man.

PMID- 30213864
TI  - Interaction mapping of the Sec61 translocon identifies two Sec61alpha regions
      interacting with hydrophobic segments in translocating chains.
AB  - Many proteins in organelles of the secretory pathway, as well as secretory
      proteins, are translocated across and inserted into the endoplasmic reticulum
      membrane by the Sec61 translocon, a protein-conducting channel. The channel
      consists of 10 transmembrane (TM) segments of the Sec61alpha subunit and
      possesses an opening between TM2b and TM7, termed the lateral gate. Structural
      and biochemical analyses of complexes of Sec61 and its ortholog SecY have
      revealed that the lateral gate is the exit for signal sequences and TM segments
      of translocating polypeptides to the lipid bilayer and also involved in the
      recognition of such hydrophobic sequences. Moreover, even marginally hydrophobic
      (mH) segments insufficient for membrane integration can be transiently stalled in
      surrounding Sec61alpha regions and cross-linked to them, but how the Sec61
      translocon accommodates these mH segments remains unclear. Here, we used Cys
      scanned variants of human Sec61alpha expressed in cultured 293-H cells to examine
      which channel regions associate with mH segments. A TM segment in a ribosome
      associated polypeptide was mainly cross-linked to positions at the lateral gate,
      whereas an mH segment in a nascent chain was cross-linked to the Sec61alpha pore
      interior positions at TM5 and TM10, as well as the lateral gate. Of note, cross
      linking at position 180 in TM5 of Sec61alpha was reduced by an I179A
      substitution. We therefore conclude that at least two Sec61alpha regions, the
      lateral gate and the pore-interior site around TM5, interact with mH segments and
      are involved in accommodating them.

PMID- 30213863
TI  - Repeat-associated non-ATG (RAN) translation.
AB  - Microsatellite expansions cause more than 40 neurological disorders, including
      Huntington's disease, myotonic dystrophy, and C9ORF72 amyotrophic lateral
      sclerosis/frontotemporal dementia (ALS/FTD). These repeat expansion mutations can
      produce repeat-associated non-ATG (RAN) proteins in all three reading frames,
      which accumulate in disease-relevant tissues. There has been considerable
      interest in RAN protein products and their downstream consequences, particularly
      for the dipeptide proteins found in C9ORF72 ALS/FTD. Understanding how RAN
      translation occurs, what cellular factors contribute to RAN protein accumulation,
      and how these proteins contribute to disease should lead to a better
      understanding of the basic mechanisms of gene expression and human disease.

PMID- 30213866
TI  - Divergent Roles for cAMP-PKA Signaling in the Regulation of Filamentous Growth in
      Saccharomyces cerevisiae and Saccharomyces bayanus.
AB  - The cyclic AMP - Protein Kinase A (cAMP-PKA) pathway is an evolutionarily
      conserved eukaryotic signaling network that is essential for growth and
      development. In the fungi, cAMP-PKA signaling plays a critical role in regulating
      cellular physiology and morphological switches in response to nutrient
      availability. We undertook a comparative investigation of the role that cAMP-PKA
      signaling plays in the regulation of filamentous growth in two closely related
      budding yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus Using
      chemical and genetic perturbations of this pathway and its downstream targets we
      discovered divergent roles for cAMP-PKA signaling in the regulation of
      filamentous growth. While cAMP-PKA signaling is required for the filamentous
      growth response in both species, increasing or decreasing the activity of this
      pathway leads to drastically different phenotypic outcomes. In S. cerevisiae,
      cAMP-PKA inhibition ameliorates the filamentous growth response while hyper
      activation of the pathway leads to increased filamentous growth; the same
      perturbations in S. bayanus result in the obverse. Divergence in the regulation
      of filamentous growth between S. cerevisiae and S. bayanus extends to downstream
      targets of PKA, including several kinases, transcription factors, and effector
      proteins. Our findings highlight the potential for significant evolutionary
      divergence in gene network function, even when the constituent parts of such
      networks are well conserved.

PMID- 30213869
TI  - GP at Hand: NHS England upholds CCG's objection to planned Birmingham expansion.

PMID- 30213867
TI  - A Drosophila CRISPR/Cas9 Toolkit for Conditionally Manipulating Gene Expression
      in the Prothoracic Gland as a Test Case for Polytene Tissues.
AB  - Targeting gene function with spatial or temporal specificity is a key goal in
      molecular genetics. CRISPR-Cas9 has greatly facilitated this strategy, but some
      standard approaches are problematic. For instance, simple tissue-specific or
      global overexpression of Cas9 can cause significant lethality or developmental
      delays even in the absence of gRNAs. In particular, we found that Gal4-mediated
      expression of UAS-Cas9 in the Drosophila prothoracic gland (PG) was not a
      suitable strategy to disrupt gene expression, since Cas9 alone caused widespread
      lethality. The PG is widely used for studying endocrine gland function during
      animal development, but tools validating PG-specific RNAi phenotypes are lacking.
      Here, we present a collection of modular gateway-compatible CRISPR-Cas9 tools
      that allow precise modulation of target gene activity with temporal and spatial
      specificity. We also demonstrate that Cas9 fused to the progesterone ligand
      binding domain can be used to activate gene expression via RU486. Using these
      approaches, we were able to avoid the lethality associated with simple GAL4
      mediated overexpression of Cas9 in the PG. Given that the PG is a polytene
      tissue, we conclude that these tools work effectively in endoreplicating cells
      where Cas9 has to target multiple copies of the same locus. Our toolkit can be
      easily adapted for other tissues and can be used both for gain- and loss-of
      function studies.

PMID- 30213868
TI  - Empirical Comparisons of Different Statistical Models To Identify and Validate
      Kernel Row Number-Associated Variants from Structured Multi-parent Mapping
      Populations of Maize.
AB  - Advances in next generation sequencing technologies and statistical approaches
      enable genome-wide dissection of phenotypic traits via genome-wide association
      studies (GWAS). Although multiple statistical approaches for conducting GWAS are
      available, the power and cross-validation rates of many approaches have been
      mostly tested using simulated data. Empirical comparisons of single variant (SV)
      and multi-variant (MV) GWAS approaches have not been conducted to test if a
      single approach or a combination of SV and MV is effective, through
      identification and cross-validation of trait-associated loci. In this study,
      kernel row number (KRN) data were collected from a set of 6,230 entries derived
      from the Nested Association Mapping (NAM) population and related populations.
      Three different types of GWAS analyses were performed: 1) single-variant (SV), 2)
      stepwise regression (STR) and 3) a Bayesian-based multi-variant (BMV) model.
      Using SV, STR, and BMV models, 257, 300, and 442 KRN-associated variants (KAVs)
      were identified in the initial GWAS analyses. Of these, 231 KAVs were subjected
      to genetic validation using three unrelated populations that were not included in
      the initial GWAS. Genetic validation results suggest that the three GWAS
      approaches are complementary. Interestingly, KAVs in low recombination regions
      were more likely to exhibit associations in independent populations than KAVs in
      recombinationally active regions, probably as a consequence of linkage
      disequilibrium. The KAVs identified in this study have the potential to enhance
      our understanding of the genetic basis of ear development.

PMID- 30213870
TI  - Ferroportin deficiency in erythroid cells causes serum iron deficiency and
      promotes hemolysis due to oxidative stress.
AB  - Ferroportin (FPN), the only known vertebrate iron exporter, transports iron from
      intestinal, splenic, and hepatic cells into the blood to provide iron to other
      tissues and cells in vivo. Most of the circulating iron is consumed by erythroid
      cells to synthesize hemoglobin. Here we found that erythroid cells not only
      consumed large amounts of iron, but also returned significant amounts of iron to
      the blood. Erythroblast-specific Fpn knockout (Fpn KO) mice developed lower serum
      iron levels in conjunction with tissue iron overload and increased FPN expression
      in spleen and liver without changing hepcidin levels. Our results also showed
      that Fpn KO mice, which suffer from mild hemolytic anemia, were sensitive to
      phenylhydrazine-induced oxidative stress but were able to tolerate iron
      deficiency upon exposure to a low-iron diet and phlebotomy, supporting that the
      anemia of Fpn KO mice resulted from erythrocytic iron overload and resulting
      oxidative injury rather than a red blood cell (RBC) production defect. Moreover,
      we found that the mean corpuscular volume (MCV) values of gain-of-function FPN
      mutation patients were positively associated with serum transferrin saturations,
      whereas MCVs of loss-of-function FPN mutation patients were not, supporting that
      erythroblasts donate iron to blood through FPN in response to serum iron levels.
      Our results indicate that FPN of erythroid cells plays an unexpectedly essential
      role in maintaining systemic iron homeostasis and protecting RBCs from oxidative
      stress, providing insight into the pathophysiology of FPN diseases.

PMID- 30213871
TI  - Hepcidin-mediated hypoferremic response to acute inflammation requires a
      threshold of Bmp6/Hjv/Smad signaling.
AB  - Systemic iron balance is controlled by hepcidin, a liver hormone that limits iron
      efflux to the bloodstream by promoting degradation of the iron exporter
      ferroportin in target cells. Iron-dependent hepcidin induction requires
      hemojuvelin (HJV), a bone morphogenetic protein (BMP) coreceptor that is
      disrupted in juvenile hemochromatosis, causing dramatic hepcidin deficiency and
      tissue iron overload. Hjv-/- mice recapitulate phenotypic hallmarks of
      hemochromatosis but exhibit blunted hepcidin induction following
      lipopolysaccharide (LPS) administration. We show that Hjv-/- mice fail to mount
      an appropriate hypoferremic response to acute inflammation caused by LPS, the
      lipopeptide FSL1, or Escherichia coli infection because residual hepcidin does
      not suffice to drastically decrease macrophage ferroportin levels. Hfe-/- mice, a
      model of milder hemochromatosis, exhibit almost wild-type inflammatory hepcidin
      expression and associated effects, whereas double Hjv-/-Hfe-/- mice phenocopy
      single Hjv-/- counterparts. In primary murine hepatocytes, Hjv deficiency does
      not affect interleukin-6 (IL-6)/Stat, and only slightly inhibits BMP2/Smad
      signaling to hepcidin; however, it severely impairs BMP6/Smad signaling and
      thereby abolishes synergism with the IL-6/Stat pathway. Inflammatory induction of
      hepcidin is suppressed in iron-deficient wild-type mice and recovers after the
      animals are provided overnight access to an iron-rich diet. We conclude that Hjv
      is required for inflammatory induction of hepcidin and controls the acute
      hypoferremic response by maintaining a threshold of Bmp6/Smad signaling. Our data
      highlight Hjv as a potential pharmacological target against anemia of
      inflammation.

PMID- 30213872
TI  - Improving CLL Vgamma9Vdelta2-T-cell fitness for cellular therapy by ex vivo
      activation and ibrutinib.
AB  - The efficacy of autologous (alphabeta) T-cell-based treatment strategies in
      chronic lymphocytic leukemia (CLL) has been modest. The Vgamma9Vdelta2-T cell
      subset consists of cytotoxic T lymphocytes with potent antilymphoma activity via
      a major histocompatibility complex-independent mechanism. We studied whether
      Vgamma9Vdelta2-T cells can be exploited as autologous effector lymphocytes in
      CLL. Healthy control Vgamma9Vdelta2-T cells were activated by and had potent
      cytolytic activity against CLL cells. However, CLL-derived Vgamma9Vdelta2-T cells
      proved dysfunctional with respect to effector cytokine production and
      degranulation, despite an increased frequency of the effector-type subset.
      Consequently, cytotoxicity against malignant B cells was hampered. A comparable
      dysfunctional phenotype was observed in healthy Vgamma9Vdelta2-T cells after
      coculture with CLL cells, indicating a leukemia-induced mechanism. Gene
      expression profiling implicated alterations in synapse formation as a conceivable
      contributor to compromised Vgamma9Vdelta2-T-cell function in CLL patients.
      Dysfunction of Vgamma9Vdelta2-T cells was fully reversible upon activation with
      autologous monocyte-derived dendritic cells (moDCs). moDC activation resulted in
      efficient expansion and predominantly yielded Vgamma9Vdelta2-T cells with a
      memory phenotype. Furthermore, ibrutinib treatment promoted an antitumor T helper
      1 (TH1) phenotype in Vgamma9Vdelta2-T cells, and we demonstrated binding of
      ibrutinib to IL-2-inducible kinase (ITK) in Vgamma9Vdelta2-T cells. Taken
      together, CLL-mediated dysfunction of autologous Vgamma9Vdelta2-T cells is fully
      reversible, resulting in potent cytotoxicity toward CLL cells. Our data support
      the potential use of Vgamma9Vdelta2-T cells as effector T cells in CLL
      immunotherapy and favor further exploration of combining Vgamma9Vdelta2-T-cell
      based therapy with ibrutinib.

PMID- 30213874
TI  - A mutation of the human EPHB2 gene leads to a major platelet functional defect.
AB  - The ephrin transmembrane receptor family of tyrosine kinases is involved in
      platelet function. We report the first EPHB2 variant affecting platelets in 2
      siblings (P1 and P2) from a consanguineous family with recurrent bleeding and
      normal platelet counts. Whole-exome sequencing identified a c.2233C>T variant
      (missense p.R745C) of the EPHB2 gene. P1 and P2 were homozygous for this variant,
      while their asymptomatic parents were heterozygous. The p.R745C variant within
      the tyrosine kinase domain was associated with defects in platelet aggregation,
      alphaIIbbeta3 activation, and granule secretion induced by G-protein-coupled
      receptor (GPCR) agonists and convulxin, as well as in thrombus formation on
      collagen under flow. In contrast, clot retraction, flow-dependent platelet
      adhesion, and spreading on fibrinogen were only mildly affected, indicating
      limited effects on alphaIIbbeta3 outside-in signaling. Most importantly, Lyn,
      Syk, and FcRgamma phosphorylation, the initial steps in glycoprotein VI (GPVI)
      platelet signaling were drastically impaired in the absence of platelet-platelet
      contact, indicating a positive role for EPHB2 in GPVI activation. Likewise
      platelet activation by PAR4-AP showed defective Src activation, as opposed to
      normal protein kinase C activity and Ca2+ mobilization. Overexpression of wild
      type and R745C EPHB2 variant in RBL-2H3 (rat basophilic leukemia) cells stably
      expressing human GPVI confirmed that EPHB2 R745C mutation impaired EPHB2
      autophosphorylation but had no effect on ephrin ligand-induced EPHB2 clustering,
      suggesting it did not interfere with EPHB2-ephrin-mediated cell-to-cell contact.
      In conclusion, this novel inherited platelet disorder affecting EPHB2
      demonstrates this tyrosine kinase receptor plays an important role in platelet
      function through crosstalk with GPVI and GPCR signaling.

PMID- 30213873
TI  - miR-150 downregulation contributes to the high-grade transformation of follicular
      lymphoma by upregulating FOXP1 levels.
AB  - Follicular lymphoma (FL) is a common indolent B-cell malignancy with a variable
      clinical course. An unfavorable event in its course is histological
      transformation to a high-grade lymphoma, typically diffuse large B-cell lymphoma.
      Recent studies show that genetic aberrations of MYC or its overexpression are
      associated with FL transformation (tFL). However, the precise molecular
      mechanisms underlying tFL are unclear. Here we performed the first profiling of
      expression of microRNAs (miRNAs) in paired samples of FL and tFL and identified 5
      miRNAs as being differentially expressed. We focused on one of these miRNAs,
      namely miR-150, which was uniformly downmodulated in all examined tFLs (~3.5
      fold), and observed that high levels of MYC are responsible for repressing miR
      150 in tFL by binding in its upstream region. This MYC-mediated repression of miR
      150 in B cells is not dependent on LIN28A/B proteins, which influence the
      maturation of miR-150 precursor (pri-miR-150) in myeloid cells. We also
      demonstrated that low miR-150 levels in tFL lead to upregulation of its target,
      namely FOXP1 protein, which is a known positive regulator of cell survival, as
      well as B-cell receptor and NF-kappaB signaling in malignant B cells. We revealed
      that low levels of miR-150 and high levels of its target, FOXP1, are associated
      with shorter overall survival in FL and suggest that miR-150 could serve as a
      good biomarker measurable in formalin-fixed paraffin-embedded tissue. Overall,
      our study demonstrates the role of the MYC/miR-150/FOXP1 axis in malignant B
      cells as a determinant of FL aggressiveness and its high-grade transformation.

PMID- 30213875
TI  - Bone marrow-specific loss of ABI1 induces myeloproliferative neoplasm with
      features resembling human myelofibrosis.
AB  - Although the pathogenesis of primary myelofibrosis (PMF) and other
      myeloproliferative neoplasms (MPNs) is linked to constitutive activation of the
      JAK-STAT pathway, JAK inhibitors have neither curative nor MPN-stem cell
      eradicating potential, indicating that other targetable mechanisms are
      contributing to the pathophysiology of MPNs. We previously demonstrated that
      Abelson interactor 1 (Abi-1), a negative regulator of Abelson kinase 1, functions
      as a tumor suppressor. Here we present data showing that bone marrow-specific
      deletion of Abi1 in a novel mouse model leads to development of an MPN-like
      phenotype resembling human PMF. Abi1 loss resulted in a significant increase in
      the activity of the Src family kinases (SFKs), STAT3, and NF-kappaB signaling. We
      also observed impairment of hematopoietic stem cell self-renewal and fitness, as
      evidenced in noncompetitive and competitive bone marrow transplant experiments.
      CD34+ hematopoietic progenitors and granulocytes from patients with PMF showed
      decreased levels of ABI1 transcript as well as increased activity of SFKs, STAT3,
      and NF-kappaB. In aggregate, our data link the loss of Abi-1 function to
      hyperactive SFKs/STAT3/NF-kappaB signaling and suggest that this signaling axis
      may represent a regulatory module involved in the molecular pathophysiology of
      PMF.

PMID- 30213876
TI  - Sex Differences in the Pharmacokinetics of Low-dose Ketamine in Plasma and Brain
      of Male and Female Rats.
AB  - Recent work from our group and others has revealed a higher sensitivity of female
      rodents to the antidepressant-like effects of the N-methyl d-aspartate receptor
      antagonist ketamine strongly influenced by circulating estrogen and progesterone
      levels. However, in the absence of any preclinical studies of pharmacokinetic sex
      differences using low-dose ketamine in rats, it is unclear whether the effects of
      sex and hormonal milieu on ketamine's behavioral actions are influenced by
      differences in ketamine metabolism between male and female rats. Therefore, this
      work examined whether sex and hormonal status affect ketamine metabolism and
      distribution in male and female rats using a low antidepressant-like dose
      selectively effective in females. Intact male rats and female rats in either
      diestrus (low estrogen, progesterone) or proestrus (high estrogen, progesterone)
      were administered low-dose ketamine, and their plasma and brains were collected
      to analyze levels of ketamine and its metabolites norketamine (NK) and
      dehydronorketamine. Females exhibited greater concentrations of ketamine and NK
      over the first 30 min following treatment in both brain and plasma, largely
      accounted for by slower clearance rates and longer half-lives. Interestingly,
      despite the impact of ovarian hormones on behavioral sensitivity to ketamine, no
      appreciable differences in pharmacokinetic parameters existed between proestrus
      and diestrus female rats. This work is the first to demonstrate sex differences
      in ketamine pharmacokinetics in rats, and suggests that while sex differences in
      metabolism may influence the amount of ketamine and NK reaching target areas in
      the brain, the impact of circulating hormone levels here is negligible.

PMID- 30213877
TI  - Assessment of Family Planning Service Availability and Readiness in 10 African
      Countries.
AB  - BACKGROUND: Access to family planning services and appropriate contraceptive
      methods is crucial for ensuring good health outcomes for women and adolescent
      girls. The World Health Organization worked with the U.S. Agency for
      International Development to develop the Service Availability and Readiness
      Assessment (SARA) survey to measure health facility capacity to provide end users
      with appropriate, high-quality health care. In this study, we looked at the
      service availability and readiness of health facilities to provide contraception
      in 10 African countries: Benin, Burkina Faso, the Democratic Republic of the
      Congo, Djibouti, Mauritania, Niger, Sierra Leone, Tanzania, Togo, and Uganda.
      METHODS: This study compared SARA survey data on family planning services from
      each of the 10 countries. We conducted a descriptive analysis of variations in
      facility readiness and the availability of services, contraceptive methods,
      trained staff, family planning guidelines, and basic health care equipment.
      RESULTS: Overall, many of the countries surveyed had a relatively high
      availability of at least 1 contraceptive method. Rural facilities tended to have
      more availability of contraception than urban facilities, and government
      facilities tended to have higher availability of family planning than other
      providers. The countries differed in their particular dominant contraceptive
      method, and stock-outs of contraceptive methods were observed. Countries had
      overall low levels of all 6 tracer items (availability of family planning
      guidelines, staff trained in family planning, blood pressure apparatuses,
      combined oral contraceptive, injectable contraceptives, and male condoms on the
      day of the assessment), indicating low health system readiness. There were
      discrepancies between reported and observed availability of blood pressure
      apparatuses and family planning guides and having at least 1 staff member trained
      to use these tools. In all countries, unmarried adolescents appeared to have less
      access to family planning than the general population. CONCLUSION: Stock-outs and
      logistics management problems were common among the countries surveyed. Critical
      gaps between reported and actual availability of products and services often
      makes it difficult for end users to access appropriate family planning methods.
      To address many of the issues, additional health worker training is needed and
      more effort to target and support adolescents should be undertaken. To achieve
      universal health coverage targets for family planning, gaps in the availability
      and readiness of health systems to provide contraceptive products and services
      must be reduced.

PMID- 30213878
TI  - A&E attendances in England are growing twice as fast as population.

PMID- 30213881
TI  - Heartbeat: improving outcomes after myocardial infarction.

PMID- 30213880
TI  - Evolutionary shift toward protein-based architecture in trypanosomal
      mitochondrial ribosomes.
AB  - Ribosomal RNA (rRNA) plays key functional and architectural roles in ribosomes.
      Using electron microscopy, we determined the atomic structure of a highly
      divergent ribosome found in mitochondria of Trypanosoma brucei, a unicellular
      parasite that causes sleeping sickness in humans. The trypanosomal mitoribosome
      features the smallest rRNAs and contains more proteins than all known ribosomes.
      The structure shows how the proteins have taken over the role of architectural
      scaffold from the rRNA: They form an autonomous outer shell that surrounds the
      entire particle and stabilizes and positions the functionally important regions
      of the rRNA. Our results also reveal the "minimal" set of conserved rRNA and
      protein components shared by all ribosomes that help us define the most essential
      functional elements.

PMID- 30213879
TI  - Functional differences of short and long isoforms of spastin harboring missense
      mutation.
AB  - Mutations of the SPG4 (SPAST) gene encoding for spastin protein are the main
      causes of hereditary spastic paraplegia. Spastin binds to microtubules and severs
      them through the enzymatic activity of its AAA domain. Several missense mutations
      located in this domain lead to stable, nonsevering spastins that decorate a
      subset of microtubules, suggesting a possible negative gain-of-function mechanism
      for these mutants. Of the two main isoforms of spastin, only mutations of the
      long isoform, M1, are supposed to be involved in the onset of the pathology,
      leaving the role of the ubiquitously expressed shorter one, M87, not fully
      investigated and understood. Here, we show that two isoforms of spastin harboring
      the same missense mutation bind and bundle different subsets of microtubules in
      HeLa cells, and likely stabilize them by increasing the level of acetylated
      tubulin. However, only mutated M1 has the ability to interact with wild-type M1,
      and decorates a subset of perinuclear microtubules associated with the
      endoplasmic reticulum that display higher resistance to microtubule
      depolymerization and increased intracellular ionic strength, compared with those
      decorated by mutated M87. We further show that only mutated M1 decorates
      microtubules of proximal axons and dendrites, and strongly impairs axonal
      transport in cortical neurons through a mechanism likely independent of the
      microtubule-severing activity of this protein.

PMID- 30213882
TI  - Control of Postprandial Hyperglycemia in Type 1 Diabetes by 24-Hour Fixed-Dose
      Coadministration of Pramlintide and Regular Human Insulin: A Randomized, Two-Way
      Crossover Study.
AB  - OBJECTIVE: Healthy pancreatic beta-cells secrete the hormones insulin and amylin
      in a fixed ratio. Both hormones are lacking in type 1 diabetes, and postprandial
      glucose control using insulin therapy alone is difficult. This study tested the
      pharmacodynamic effects of the amylin analog pramlintide and insulin delivered in
      a fixed ratio over a 24-h period. RESEARCH DESIGN AND METHODS: Patients with type
      1 diabetes were stabilized on insulin pump therapy with insulin lispro before a
      randomized, single-masked, two-way crossover, 24-h inpatient study in which
      regular human insulin was administered with pramlintide or placebo using separate
      infusion pumps in a fixed ratio (9 MUg/unit). Meal content and timing and patient
      specific insulin doses were the same with each treatment. The primary outcome
      measure was change in mean glucose by continuous glucose monitoring (CGM).
      Profiles of laboratory-measured glucose, insulin, glucagon, and triglycerides
      were also compared. RESULTS: Mean 24-h glucose measured by CGM was lower with
      pramlintide versus placebo (8.5 vs. 9.7 mmol/L, respectively; P = 0.012) due to a
      marked reduction of postprandial increments. Glycemic variability was reduced,
      and postprandial glucagon and triglycerides were also lower with pramlintide
      versus placebo. Gastrointestinal side effects were more frequent during use of
      pramlintide; no major hypoglycemic events occurred with pramlintide or placebo.
      CONCLUSIONS: Coadministration of fixed-ratio pramlintide and regular human
      insulin for 24 h improved postprandial hyperglycemia and glycemic variability in
      patients with type 1 diabetes. Longer studies including dose titration under
      daily conditions are needed to determine whether this regimen could provide long
      term improvement of glycemic control.

PMID- 30213883
TI  - Estimated Resting Metabolic Rate and Body Composition Measures Are Strongly
      Associated With Diabetic Retinopathy in Indonesian Adults With Type 2 Diabetes.
AB  - OBJECTIVE: To investigate the associations of estimated resting metabolic rate
      (RMR), body fat (BF), subcutaneous fat (SCF), visceral fat (VF), fat-free mass
      (FFM) percentage, BMI, and waist circumference (WC) with diabetic retinopathy
      (DR) in Indonesian adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: This
      was a community-based cross-sectional study of 1,184 subjects with type 2
      diabetes. DR was assessed from fundus photography and categorized as mild,
      moderate nonproliferative DR (NPDR), and vision-threatening DR (VTDR). RMR and
      body composition parameters were measured using automated body composition scan.
      Logistic regression with semipartial correlation analysis was used. RESULTS: DR
      and VTDR were present in 43.1 and 26.3% of participants, respectively. After
      adjustment for age, sex, diabetes duration, fasting glucose, systolic blood
      pressure, smoking, diabetic ulcer, and use of combined diabetes treatment, per SD
      increase in RMR (odds ratio [OR] 2.60 [95% CI 2.19-3.07]; P < 0.001) was
      associated with DR, while per SD increases in BF (0.66 [95% CI 0.56-0.78]; P <
      0.001), FFM (0.69 [0.57-0.84]; P < 0.001), VF (0.77 [0.67-0.88]; P < 0.001), BMI
      (0.83 [0.73-0.94]; P = 0.004), and WC (0.81 [0.73-0.91]; P < 0.001) were
      inversely associated with presence of DR. Similar associations were found for
      VTDR. Among all variables, RMR had the largest contribution to the variance in
      the DR model (39%). CONCLUSIONS: In this study, RMR and body composition measures
      were strongly associated with and contributed considerably to the presence and
      severity of DR. These findings, if confirmed, suggest that RMR and body
      composition may be strong markers that represent actual metabolic state in the
      pathophysiology of DR.

PMID- 30213884
TI  - Differential IL-2 expression defines developmental fates of follicular versus
      nonfollicular helper T cells.
AB  - In response to infection, naive CD4+ T cells differentiate into two
      subpopulations: T follicular helper (TFH) cells, which support B cell antibody
      production, and non-TFH cells, which enhance innate immune cell functions.
      Interleukin-2 (IL-2), the major cytokine produced by naive T cells, plays an
      important role in the developmental divergence of these populations. However, the
      relationship between IL-2 production and fate determination remains unclear.
      Using reporter mice, we found that differential production of IL-2 by naive CD4+
      T cells defined precursors fated for different immune functions. IL-2 producers,
      which were fated to become TFH cells, delivered IL-2 to nonproducers destined to
      become non-TFH cells. Because IL-2 production was limited to cells receiving the
      strongest T cell receptor (TCR) signals, a direct link between TCR-signal
      strength, IL-2 production, and T cell fate determination has been established.

PMID- 30213885
TI  - Recurrent cortical circuits implement concentration-invariant odor coding.
AB  - Animals rely on olfaction to find food, attract mates, and avoid predators. To
      support these behaviors, they must be able to identify odors across different
      odorant concentrations. The neural circuit operations that implement this
      concentration invariance remain unclear. We found that despite concentration
      dependence in the olfactory bulb (OB), representations of odor identity were
      preserved downstream, in the piriform cortex (PCx). The OB cells responding
      earliest after inhalation drove robust responses in sparse subsets of PCx
      neurons. Recurrent collateral connections broadcast their activation across the
      PCx, recruiting global feedback inhibition that rapidly truncated and suppressed
      cortical activity for the remainder of the sniff, discounting the impact of
      slower, concentration-dependent OB inputs. Eliminating recurrent collateral
      output amplified PCx odor responses rendered the cortex steeply concentration
      dependent and abolished concentration-invariant identity decoding.

PMID- 30213886
TI  - Asymmetric phosphoric acid-catalyzed four-component Ugi reaction.
AB  - The Ugi reaction constructs alpha-acylaminoamide compounds by combining an
      aldehyde or ketone, an amine, a carboxylic acid, and an isocyanide in a single
      flask. Its appealing features include inherent atom and step economy together
      with the potential to generate products of broad structural diversity. However,
      control of the stereochemistry in this reaction has proven to be a formidable
      challenge. We describe an efficient enantioselective four-component Ugi reaction
      catalyzed by a chiral phosphoric acid derivative that delivers more than 80 alpha
      acylaminoamides in good to excellent enantiomeric excess. Experimental and
      computational studies establish the reaction mechanism and origins of
      stereoselectivity.

PMID- 30213887
TI  - Response to Comment on "Unexpected reversal of C3 versus C4 grass response to
      elevated CO2 during a 20-year field experiment".
AB  - Nie and colleagues suggest a key role for interannual climate variation as an
      explanation for the temporal dynamics of an unexpected 20-year reversal of
      biomass responses of C3-C4 grasses to elevated CO2 However, we had already
      identified some climate-dependent differences in C3 and C4 responses to eCO2 and
      shown that these could not fully explain the temporal dynamics we observed.

PMID- 30213888
TI  - Space for nature.

PMID- 30213889
TI  - News at a glance.

PMID- 30213890
TI  - Physicists plan hunt for Higgs boson pairs.

PMID- 30213891
TI  - Steep drop in Zika cases undermines vaccine trial.

PMID- 30213892
TI  - New cancer-fighting cells enter trials.

PMID- 30213893
TI  - NASA space laser targets melting poles.

PMID- 30213894
TI  - Scarred bird bones reveal early settlement on Madagascar.

PMID- 30213895
TI  - Piercing the haze.

PMID- 30213896
TI  - Windfall.

PMID- 30213897
TI  - Gaia 2.0.

PMID- 30213898
TI  - Nervous system-like signaling in plant defense.

PMID- 30213899
TI  - A pinch of RNA spices up DNA repair.

PMID- 30213900
TI  - Revving up an artificial metalloenzyme.

PMID- 30213901
TI  - Enantioselective four-component Ugi reactions.

PMID- 30213902
TI  - Robotic-flapper maneuvers and fruitfly turns.

PMID- 30213903
TI  - A "technology-smart" battery policy strategy for Europe.

PMID- 30213904
TI  - Grazing limits benefited Bridge Creek.

PMID- 30213905
TI  - U.S. fast test reactor will pay dividends.

PMID- 30213906
TI  - Prioritizing population policies.

PMID- 30213907
TI  - A tailless aerial robotic flapper reveals that flies use torque coupling in rapid
      banked turns.
AB  - Insects are among the most agile natural flyers. Hypotheses on their flight
      control cannot always be validated by experiments with animals or tethered
      robots. To this end, we developed a programmable and agile autonomous free-flying
      robot controlled through bio-inspired motion changes of its flapping wings.
      Despite being 55 times the size of a fruit fly, the robot can accurately mimic
      the rapid escape maneuvers of flies, including a correcting yaw rotation toward
      the escape heading. Because the robot's yaw control was turned off, we showed
      that these yaw rotations result from passive, translation-induced aerodynamic
      coupling between the yaw torque and the roll and pitch torques produced
      throughout the maneuver. The robot enables new methods for studying animal
      flight, and its flight characteristics allow for real-world flight missions.

PMID- 30213908
TI  - A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the
      native enzyme.
AB  - Multielectron redox reactions often require multicofactor metalloenzymes to
      facilitate coupled electron and proton movement, but it is challenging to design
      artificial enzymes to catalyze these important reactions, owing to their
      structural and functional complexity. We report a designed heteronuclear heme
      [4Fe-4S] cofactor in cytochrome c peroxidase as a structural and functional model
      of the enzyme sulfite reductase. The initial model exhibits spectroscopic and
      ligand-binding properties of the native enzyme, and sulfite reduction activity
      was improved-through rational tuning of the secondary sphere interactions around
      the [4Fe-4S] and the substrate-binding sites-to be close to that of the native
      enzyme. By offering insight into the requirements for a demanding six-electron,
      seven-proton reaction that has so far eluded synthetic catalysts, this study
      provides strategies for designing highly functional multicofactor artificial
      enzymes.

PMID- 30213909
TI  - Quantum entanglement of the spin and orbital angular momentum of photons using
      metamaterials.
AB  - Metamaterials constructed from deep subwavelength building blocks have been used
      to demonstrate phenomena ranging from negative refractive index and epsilon-near
      zero to cloaking, emulations of general relativity, and superresolution imaging.
      More recently, metamaterials have been suggested as a new platform for quantum
      optics. We present the use of a dielectric metasurface to generate entanglement
      between the spin and orbital angular momentum of photons. We demonstrate the
      generation of the four Bell states on a single photon by using the geometric
      phase that arises from the photonic spin-orbit interaction and subsequently show
      nonlocal correlations between two photons that interacted with the metasurface.
      Our results show that metamaterials are suitable for the generation and
      manipulation of entangled photon states, introducing the area of quantum optics
      metamaterials.

PMID- 30213910
TI  - Quantum metasurface for multiphoton interference and state reconstruction.
AB  - Metasurfaces based on resonant nanophotonic structures have enabled innovative
      types of flat-optics devices that often outperform the capabilities of bulk
      components, yet these advances remain largely unexplored for quantum
      applications. We show that nonclassical multiphoton interferences can be achieved
      at the subwavelength scale in all-dielectric metasurfaces. We simultaneously
      image multiple projections of quantum states with a single metasurface, enabling
      a robust reconstruction of amplitude, phase, coherence, and entanglement of
      multiphoton polarization-encoded states. One- and two-photon states are
      reconstructed through nonlocal photon correlation measurements with polarization
      insensitive click detectors positioned after the metasurface, and the scalability
      to higher photon numbers is established theoretically. Our work illustrates the
      feasibility of ultrathin quantum metadevices for the manipulation and measurement
      of multiphoton quantum states, with applications in free-space quantum imaging
      and communications.

PMID- 30213911
TI  - Classifying drivers of global forest loss.
AB  - Global maps of forest loss depict the scale and magnitude of forest disturbance,
      yet companies, governments, and nongovernmental organizations need to distinguish
      permanent conversion (i.e., deforestation) from temporary loss from forestry or
      wildfire. Using satellite imagery, we developed a forest loss classification
      model to determine a spatial attribution of forest disturbance to the dominant
      drivers of land cover and land use change over the period 2001 to 2015. Our
      results indicate that 27% of global forest loss can be attributed to
      deforestation through permanent land use change for commodity production. The
      remaining areas maintained the same land use over 15 years; in those areas, loss
      was attributed to forestry (26%), shifting agriculture (24%), and wildfire (23%).
      Despite corporate commitments, the rate of commodity-driven deforestation has not
      declined. To end deforestation, companies must eliminate 5 million hectares of
      conversion from supply chains each year.

PMID- 30213912
TI  - Glutamate triggers long-distance, calcium-based plant defense signaling.
AB  - Animals require rapid, long-range molecular signaling networks to integrate
      sensing and response throughout their bodies. The amino acid glutamate acts as an
      excitatory neurotransmitter in the vertebrate central nervous system,
      facilitating long-range information exchange via activation of glutamate receptor
      channels. Similarly, plants sense local signals, such as herbivore attack, and
      transmit this information throughout the plant body to rapidly activate defense
      responses in undamaged parts. Here we show that glutamate is a wound signal in
      plants. Ion channels of the GLUTAMATE RECEPTOR-LIKE family act as sensors that
      convert this signal into an increase in intracellular calcium ion concentration
      that propagates to distant organs, where defense responses are then induced.

PMID- 30213913
TI  - A continental system for forecasting bird migration.
AB  - Billions of animals cross the globe each year during seasonal migrations, but
      efforts to monitor them are hampered by the unpredictability of their movements.
      We developed a bird migration forecast system at a continental scale by
      leveraging 23 years of spring observations to identify associations between
      atmospheric conditions and bird migration intensity. Our models explained up to
      81% of variation in migration intensity across the United States at altitudes of
      0 to 3000 meters, and performance remained high in forecasting events 1 to 7 days
      in advance (62 to 76% of variation was explained). Avian migratory movements
      across the United States likely exceed 500 million individuals per night during
      peak passage. Bird migration forecasts will reduce collisions with buildings,
      airplanes, and wind turbines; inform a variety of monitoring efforts; and engage
      the public.

PMID- 30213914
TI  - An ER surface retrieval pathway safeguards the import of mitochondrial membrane
      proteins in yeast.
AB  - The majority of organellar proteins are translated on cytosolic ribosomes and
      must be sorted correctly to function. Targeting routes have been identified for
      organelles such as peroxisomes and the endoplasmic reticulum (ER). However,
      little is known about the initial steps of targeting of mitochondrial proteins.
      In this study, we used a genome-wide screen in yeast and identified factors
      critical for the intracellular sorting of the mitochondrial inner membrane
      protein Oxa1. The screen uncovered an unexpected path, termed ER-SURF, for
      targeting of mitochondrial membrane proteins. This pathway retrieves
      mitochondrial proteins from the ER surface and reroutes them to mitochondria with
      the aid of the ER-localized chaperone Djp1. Hence, cells use the expanse of the
      ER surfaces as a fail-safe to maximize productive mitochondrial protein
      targeting.

PMID- 30213915
TI  - Semisynthetic sensor proteins enable metabolic assays at the point of care.
AB  - Monitoring metabolites at the point of care could improve the diagnosis and
      management of numerous diseases. Yet for most metabolites, such assays are not
      available. We introduce semisynthetic, light-emitting sensor proteins for use in
      paper-based metabolic assays. The metabolite is oxidized by nicotinamide adenine
      dinucleotide phosphate, and the sensor changes color in the presence of the
      reduced cofactor, enabling metabolite quantification with the use of a digital
      camera. The approach makes any metabolite that can be oxidized by the cofactor a
      candidate for quantitative point-of-care assays, as shown for phenylalanine,
      glucose, and glutamate. Phenylalanine blood levels of phenylketonuria patients
      were analyzed at the point of care within minutes with only 0.5 microliters of
      blood. Results were within 15% of those obtained with standard testing methods.

PMID- 30213917
TI  - Learning to lead.

PMID- 30213918
TI  - Role model: Hugh Herzig.

PMID- 30213916
TI  - Ribonucleotide incorporation enables repair of chromosome breaks by nonhomologous
      end joining.
AB  - The nonhomologous end-joining (NHEJ) pathway preserves genome stability by
      ligating the ends of broken chromosomes together. It employs end-processing
      enzymes, including polymerases, to prepare ends for ligation. We show that two
      such polymerases incorporate primarily ribonucleotides during NHEJ-an exception
      to the central dogma of molecular biology-both during repair of chromosome breaks
      made by Cas9 and during V(D)J recombination. Moreover, additions of
      ribonucleotides but not deoxynucleotides effectively promote ligation. Repair
      kinetics suggest that ribonucleotide-dependent first-strand ligation is followed
      by complementary strand repair with deoxynucleotides, then by replacement of
      ribonucleotides embedded in the first strand with deoxynucleotides. Our results
      indicate that as much as 65% of cellular NHEJ products have transiently embedded
      ribonucleotides, which promote flexibility in repair at the cost of more fragile
      intermediates.

PMID- 30213919
TI  - Toxoplasma gondii seropositivity and substance use in US adults.
AB  - The intracellular parasite Toxoplasma gondii (Nicolle et Manceaux, 1908) infects
      humans resulting in acute toxoplasmosis, an infection that in immunocompetent
      people is typically mild but results in persistent latent toxoplasmosis. In that
      T. gondii appears to affect dopamine synthesis and because addicting drugs affect
      midbrain dopamine transmission, latent toxoplasmosis could influence substance
      use. Using both the third and continuous National Health and Nutrition
      Examination Surveys from the US Centers for Disease Control and Prevention, we
      used logistic regression to test for associations between T. gondii
      seropositivity and subject self-report of having ever used tobacco, alcohol,
      marijuana, cocaine, heroin, or methamphetamine. In the third NHANES dataset,
      which included data for tobacco, alcohol, marijuana and cocaine, T. gondii
      seropositivity was associated with a reduced likelihood of self-reported
      marijuana (OR = 0.71 [95% CI: 0.58; 0.87]; p = 0.001) and cocaine use (OR = 0.72
      [95% CI: 0.56; 0.91]; p = 0.006). In the continuous National Health and Nutrition
      Examination Surveys dataset, which included data for all six substances, T.
      gondii seropositivity was associated with a reduced likelihood of self-reported
      tobacco (OR = 0.87 [95% CI: 0.76; 1.00]; p = 0.044), marijuana (OR = 0.60 [95%
      CI: 0.50; 0.72]; p < 0.001), heroin (OR = 0.60 [95% CI: 0.42; 0.85]; p = 0.005)
      and methamphetamine use (OR = 0.54 [95% CI: 0.38; 0.77]; p = 0.001). We observed
      interactions between sex and T. gondii seropositivity in the prediction of self
      reported use of tobacco and alcohol. Further, T. gondii seropositivity appeared
      to remove the protective effect of education and economic status against self
      reported cigarette smoking. These findings suggest that T. gondii seropositivity
      may be inversely associated with some but not all types of substance use in US
      adults.

PMID- 30213920
TI  - Fabrication of a silver nanoparticle-coated collagen membrane with anti-bacterial
      and anti-inflammatory activities for guided bone regeneration.
AB  - Alveolar bone loss is a common problem that affects dental implant placement. A
      barrier between the bone substitute and gingiva that can prevent fibro-tissue
      ingrowth, bacterial infection and induce bone formation is a key factor in
      improving the success of alveolar ridge reconstruction. This study aims to
      develop a bioactive collagen barrier material for guided bone regeneration, that
      is coupled with anti-bacterial and anti-inflammatory properties. We have
      evaluated two silver coating methods and found controllable and precise coating
      achieved by sonication compared with sputtering. The optimized AgNP-coated
      collagen membrane exhibited excellent anti-bacterial effects against
      Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) with
      limited cellular toxicity. It also displayed effective anti-inflammatory effects
      by reducing the expression and release of inflammatory cytokines including IL-6
      and TNF-alpha. Additionally, AgNP-coated collagen membranes were able to induce
      osteogenic differentiation of mesenchymal stem cells that guide bone
      regeneration. These findings demonstrate the potential application of AgNP-coated
      collagen membranes to prevent infection after bone graft introduction in alveolar
      ridge reconstruction.

PMID- 30213921
TI  - Feasibility and diagnostic accuracy of an electronic nose in children with asthma
      and cystic fibrosis.
AB  - The measurement of volatile organic compounds (VOCs) in exhaled breath is a
      promising tool for diagnosing and monitoring various lung diseases in children.
      Gas chromatography mass spectrometry (GC-MS) analysis is a frequently used
      standard technique for VOCs analysis. However, as GC-MS is an expensive and time
      consuming technique, hand-held devices or electronic noses (eNoses) have been
      developed. Recently, the Aeonose was introduced as an easy-to-use handheld eNose
      capable of point-of-care testing. Although first results using this eNose in
      adults are promising, studies in children are lacking. We therefore performed a
      cross-sectional study in 55 children and adolescents >= 6 years of age (20
      children with moderate to severe asthma, 13 children with CF, and 22 healthy
      controls). The feasibility of the Aeonose was high (> 98% successful
      measurements). The diagnostic accuracy was high for discriminating asthma from CF
      (Area Under the Receiver Operating Characteristic Curve [AUC] 0.90 [95%
      Confidence Interval (CI) 0.78-1.00] sensitivity 89% [65-98%], specificity 77% [46
      94%]), and for the distinction between CF and healthy controls (AUC 0.87 [0.74
      1.00], sensitivity 85% [54-97%], specificity 77% [54-91%]). However, the
      diagnostic accuracy for the discrimination between asthma and healthy controls
      was modest (AUC 0.79 [0.63-0.94], sensitivity 74% [49-90%], specificity 91% [69
      98%]). This is the first study to report test results of the Aeonose in children
      and adolescents >= 6 years. This eNose showed a high feasibility with modest to
      good diagnostic accuracies in asthma and CF. &#13; This study was registered at
      clinicaltrial.gov (NCT 03377686).

PMID- 30213922
TI  - Marker-assisted selection of YY supermales from a genetically improved farmed
      tilapia-derived strain.
AB  - Genetically improved farmed tilapia (GIFT) and GIFT-derived strains account for
      the majority of farmed tilapia worldwide. As male tilapias grow much faster than
      females, they are often considered more desirable in the aquacultural industry.
      Sex reversal of females to males using the male sex hormone 17-alpha
      methyltestosterone (MT) is generally used to induce phenotypic males during large
      scale production of all male fingerlings. However, the widespread use of large
      quantities of sex reversal hormone in hatcheries may pose a health risk to
      workers and ecological threats to surrounding environments. Breeding procedures
      to produce genetically all-male tilapia with limited or no use of sex hormones
      are therefore urgently needed. In this study, by applying marker-assisted
      selection (MAS) for the selection of YY supermales from a GIFT-derived strain, we
      identified 24 XY pseudofemale and 431 YY supermale tilapias. Further performance
      evaluation on the progenies of the YY supermales resulted in male rates of 94.1%,
      99.5% and 99.6%, respectively, in three populations, and a daily increase in body
      weight of 1.4 g at 3 months (n=997). Our study established a highly effective MAS
      procedure in the selection of YY supermales from a GIFT-derived strain.
      Furthermore, the development of MAS-selected YY supermales will help reduce the
      utilization of hormones for controlling sex in the tilapia aquaculture.

PMID- 30213923
TI  - Dual Cestode Infection in a Thai Patient (Spinal Sparganosis and Racemose
      Neurocysticercosis): A Case Report.
AB  - BACKGROUND Spinal sparganosis and racemose (grape-like) neurocysticercosis are
      rare diseases. Co-infection with spinal sparganosis and racemose
      neurocysticercosis has never been reported in the English-language literature.
      CASE REPORT A 41-year-old male presented after having experienced left hip pain
      with radiation to the leg, progressive weakness and numbness of the left leg, and
      difficulty urinating for 4 years, all of which was caused by spinal sparganosis.
      He had also experienced progressive vision and hearing loss on the right side for
      3 years, which were caused by racemose neurocysticercosis. Magnetic resonance
      imaging (MRI) of the lumbosacral spine and the brain revealed intrinsic spinal
      cord lesion and racemose neurocysticercosis, respectively. Spinal sparganosis was
      diagnosed by histological examination and an immunochromatographic test. It was
      treated with a high-dose of praziquantel (75 mg/kg/day) combined with cimetidine;
      without clinical improvement. Treatment consisted of racemose neurocysticercosis
      with albendazole for 2 months. A follow-up MRI of the brain revealed a minimal
      reduction in the amount of racemose neurocysticercosis. Repeat treatment with
      albendazole was administered. However, further MRI examination of the brain
      revealed the condition to be unchanged. Vision and hearing loss had also not
      improved. CONCLUSIONS In this case report, we describe a middle-aged man who
      presented with spinal cord symptoms (hip pain, progressive weakness and numbness
      of the leg, and difficulty urinating) and cranial nerve palsies (vision and
      hearing loss) caused by spinal sparganosis and racemose neurocysticercosis,
      respectively. Neurological symptoms did not improve with anthelmintic drugs.

PMID- 30213924
TI  - Factors in Organ Donation Coordinators: A Cross-Sectional Study in China.
AB  - BACKGROUND Organ donation coordinators play an important role in the organ
      transplantation process. Job burnout can seriously affect their turnover rates
      and the organ donation rate. The present study investigated the level of job
      burnout and its related factors among organ donation coordinators in China.
      MATERIAL AND METHODS From March to May 2017, we administered questionnaire
      surveys to 320 organ donation coordinators from 32 cities. The questionnaire
      included the following: the Chinese version of MBI-GS was used to evaluate the
      burnout levels of organ donation coordinators, the Chinese version of GSES was
      used to assess related personal factors, and the Job Demands Scale and the SSRS
      were used to evaluate related environmental factors. RESULTS We received a total
      of 283 questionnaires with a response rate of 88.4%. Out of 283 organ donation
      coordinators, 169 coordinators (59.7%) showed burnout symptoms. Among them, 161
      (56.9%) had mild burnout and 8 (2.8%) had severe burnout. Analysis by multiple
      linear regression reveals that gender, marital status, educational level, work
      unit, type of coordinator, job demands, self-efficacy, social support, and job
      satisfaction are the main factors affecting job burnout in organ donation
      coordinators. CONCLUSIONS The prevalence of job burnout among Chinese organ
      donation coordinators is relatively high, with mild burnout as the main symptom
      and reduced personal accomplishment as the main clinical feature. We hope this
      study will provide a reference for the recruitment and reduction of coordinator
      burnout.

PMID- 30213925
TI  - Identification of Key Pathways and Genes in Anaplastic Thyroid Carcinoma via
      Integrated Bioinformatics Analysis.
AB  - BACKGROUND To provide a better understanding of anaplastic thyroid carcinoma
      (ATC) at the molecular level, this study aimed to identify the genes and key
      pathways associated with ATC by using integrated bioinformatics analysis.
      MATERIAL AND METHODS Based on the microarray data GSE9115, GSE65144, and GSE53072
      derived from the Gene Expression Omnibus, the differentially expressed genes
      (DEGs) between ATC samples and normal controls were identified. With DEGs, we
      performed a series of functional enrichment analyses. Then, a protein-protein
      interaction (PPI) network was constructed and visualized, with which the hub gene
      nodes were screened out. Finally, modules analysis for the PPI network was
      performed to further investigate the potential relationships between DEGs and
      ATC. RESULTS A total of 537 common DEGs were screened out from all 3 datasets,
      among which 247 genes were upregulated and 275 genes were downregulated. GO
      analysis indicated that upregulated DEGs were mainly involved in cell division
      and mitotic nuclear division and the downregulated DEGs were significantly
      enriched in ventricular cardiac muscle cell action potential. KEGG pathway
      analysis showed that the upregulated DEGs were mainly enriched in cell cycle and
      ECM-receptor interaction and the downregulated DEGs were mainly enriched in
      thyroid hormone synthesis, insulin resistance, and pathways in cancer. The top 10
      hub genes in the constructed PPI network were CDK1, CCNB1, TOP2A, AURKB, CCNA2,
      BUB1, AURKA, CDC20, MAD2L1, and BUB1B. The modules analysis showed that genes in
      the top 2 significant modules of PPI network were mainly associated with mitotic
      cell cycle and positive regulation of mitosis, respectively. CONCLUSIONS We
      identified a series of key genes along with the pathways that were most closely
      related with ATC initiation and progression. Our results provide a more detailed
      molecular mechanism for the development of ATC, shedding light on the potential
      biomarkers and therapeutic targets.

PMID- 30213926
TI  - Influence of surface atomic structure demonstrated on oxygen incorporation
      mechanism at a model perovskite oxide.
AB  - Perovskite oxide surfaces catalyze oxygen exchange reactions that are crucial for
      fuel cells, electrolyzers, and thermochemical fuel synthesis. Here, by bridging
      the gap between surface analysis with atomic resolution and oxygen exchange
      kinetics measurements, we demonstrate how the exact surface atomic structure can
      determine the reactivity for oxygen exchange reactions on a model perovskite
      oxide. Two precisely controlled surface reconstructions with (4 * 1) and (2 * 5)
      symmetry on 0.5 wt.% Nb-doped SrTiO3(110) were subjected to isotopically labeled
      oxygen exchange at 450  degrees C. The oxygen incorporation rate is three times
      higher on the (4 * 1) surface phase compared to the (2 * 5). Common models of
      surface reactivity based on the availability of oxygen vacancies or on the ease
      of electron transfer cannot account for this difference. We propose a structure
      driven oxygen exchange mechanism, relying on the flexibility of the surface
      coordination polyhedra that transform upon dissociation of oxygen molecules.

PMID- 30213927
TI  - Revealing the biexciton and trion-exciton complexes in BN encapsulated WSe2.
AB  - Strong Coulomb interactions in single-layer transition metal dichalcogenides
      (TMDs) result in the emergence of strongly bound excitons, trions, and
      biexcitons. These excitonic complexes possess the valley degree of freedom, which
      can be exploited for quantum optoelectronics. However, in contrast to the good
      understanding of the exciton and trion properties, the binding energy of the
      biexciton remains elusive, with theoretical calculations and experimental studies
      reporting discrepant results. In this work, we resolve the conflict by employing
      low-temperature photoluminescence spectroscopy to identify the biexciton state in
      BN-encapsulated single-layer WSe2. The biexciton state only exists in charge
      neutral WSe2, which is realized through the control of efficient electrostatic
      gating. In the lightly electron-doped WSe2, one free electron binds to a
      biexciton and forms the trion-exciton complex. Improved understanding of the
      biexciton and trion-exciton complexes paves the way for exploiting the many-body
      physics in TMDs for novel optoelectronics applications.

PMID- 30213929
TI  - Nonlocal electron correlations in an itinerant ferromagnet.
AB  - Our understanding of the properties of ferromagnetic materials, widely used in
      spintronic devices, is fundamentally based on their electronic band structure.
      However, even for the most simple elemental ferromagnets, electron correlations
      are prevalent, requiring descriptions of their electronic structure beyond the
      simple picture of independent quasi-particles. Here, we give evidence that in
      itinerant ferromagnets like cobalt these electron correlations are of nonlocal
      origin, manifested in a complex self-energy Sigmasigma(E,k) that disperses as
      function of spin sigma, energy E, and momentum vector k. Together with one-step
      photoemission calculations, our experiments allow us to quantify the dispersive
      behaviour of the complex self-energy over the whole Brillouin zone. At the same
      time we observe regions of anomalously large "waterfall"-like band
      renormalization, previously only attributed to strong electron correlations in
      high-TC superconductors, making itinerant ferromagnets a paradigmatic test case
      for the interplay between band structure, magnetism, and many-body correlations.

PMID- 30213931
TI  - Hierarchical rupture growth evidenced by the initial seismic waveforms.
AB  - The ability to predict the eventual size of an earthquake during its early growth
      stage is a crucial component of earthquake early warning systems. Recent studies
      have revealed that the onsets of small and large earthquakes are variable but
      statistically indistinguishable. However, it is unknown whether small and large
      earthquakes can share the same processes at the same location. Here we show clear
      evidence of almost identical growth processes shared by repeating earthquakes of
      various sizes that have occurred in the Naka region, eastern Japan. Our results
      indicate that a large earthquake is a failure with a large characteristic spatial
      scale that is initially triggered by a failure with a small characteristic scale,
      which may also occur independently controlled by subtle differences in the
      physical conditions, suggesting the existence of a hierarchical structure on the
      plate interface. Earthquakes are random, but they may also be controlled by such
      structures.

PMID- 30213930
TI  - Evaluating climate geoengineering proposals in the context of the Paris Agreement
      temperature goals.
AB  - Current mitigation efforts and existing future commitments are inadequate to
      accomplish the Paris Agreement temperature goals. In light of this, research and
      debate are intensifying on the possibilities of additionally employing proposed
      climate geoengineering technologies, either through atmospheric carbon dioxide
      removal or farther-reaching interventions altering the Earth's radiative energy
      budget. Although research indicates that several techniques may eventually have
      the physical potential to contribute to limiting climate change, all are in early
      stages of development, involve substantial uncertainties and risks, and raise
      ethical and governance dilemmas. Based on present knowledge, climate
      geoengineering techniques cannot be relied on to significantly contribute to
      meeting the Paris Agreement temperature goals.

PMID- 30213932
TI  - Triboelectric microplasma powered by mechanical stimuli.
AB  - Triboelectric nanogenerators (TENGs) naturally have the capability of high
      voltage output to breakdown gas easily. Here we present a concept of
      triboelectric microplasma by integrating TENGs with the plasma source so that
      atmospheric-pressure plasma can be powered only by mechanical stimuli. Four
      classical atmospheric-pressure microplasma sources are successfully demonstrated,
      including dielectric barrier discharge (DBD), atmospheric-pressure non
      equilibrium plasma jets (APNP-J), corona discharge, and microspark discharge. For
      these types of microplasma, analysis of electric characteristics, optical
      emission spectra, COMSOL simulation and equivalent circuit model are carried out
      to explain transient process of different discharge. The triboelectric
      microplasma has been applied to patterned luminescence and surface treatment
      successfully as a first-step evaluation as well as to prove the system
      feasibility. This work offers a promising, facile, portable and safe supplement
      to traditional plasma sources, and will enrich the diversity of plasma
      applications based on the reach of existing technologies.

PMID- 30213933
TI  - Seed-mediated atomic-scale reconstruction of silver manganate nanoplates for
      oxygen reduction towards high-energy aluminum-air flow batteries.
AB  - Aluminum-air batteries are promising candidates for next-generation high-energy
      density storage, but the inherent limitations hinder their practical use. Here,
      we show that silver nanoparticle-mediated silver manganate nanoplates are a
      highly active and chemically stable catalyst for oxygen reduction in alkaline
      media. By means of atomic-resolved transmission electron microscopy, we find that
      the formation of stripe patterns on the surface of a silver manganate nanoplate
      originates from the zigzag atomic arrangement of silver and manganese, creating a
      high concentration of dislocations in the crystal lattice. This structure can
      provide high electrical conductivity with low electrode resistance and abundant
      active sites for ion adsorption. The catalyst exhibits outstanding performance in
      a flow-based aluminum-air battery, demonstrating high gravimetric and volumetric
      energy densities of ~2552 Wh kgAl-1 and ~6890 Wh lAl-1 at 100 mA cm-2, as well as
      high stability during a mechanical recharging process.

PMID- 30213935
TI  - Hepatorenal syndrome.

PMID- 30213928
TI  - Identification of multiple risk loci and regulatory mechanisms influencing
      susceptibility to multiple myeloma.
AB  - Genome-wide association studies (GWAS) have transformed our understanding of
      susceptibility to multiple myeloma (MM), but much of the heritability remains
      unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a
      replication series, totalling 9974 MM cases and 247,556 controls of European
      ancestry. Collectively, these data provide evidence for six new MM risk loci,
      bringing the total number to 23. Integration of information from gene expression,
      epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate
      disruption of developmental transcriptional regulators as a basis of MM
      susceptibility, compatible with altered B-cell differentiation as a key
      mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature
      as recurrently perturbed pathways. Our findings provide further insight into the
      biological basis of MM.

PMID- 30213934
TI  - Crystal structure of TcpK in complex with oriT DNA of the antibiotic resistance
      plasmid pCW3.
AB  - Conjugation is fundamental for the acquisition of new genetic traits and the
      development of antibiotic resistance in pathogenic organisms. Here, we show that
      a hypothetical Clostridium perfringens protein, TcpK, which is encoded by the
      tetracycline resistance plasmid pCW3, is essential for efficient conjugative DNA
      transfer. Our studies reveal that TcpK is a member of the winged helix-turn-helix
      (wHTH) transcription factor superfamily and that it forms a dimer in solution.
      Furthermore, TcpK specifically binds to a nine-nucleotide sequence that is
      present as tandem repeats within the pCW3 origin of transfer (oriT). The X-ray
      crystal structure of the TcpK-TcpK box complex reveals a binding mode centered on
      and around the beta-wing, which is different from what has been previously shown
      for other wHTH proteins. Structure-guided mutagenesis experiments validate the
      specific interaction between TcpK and the DNA molecule. Additional studies
      highlight that the TcpK dimer is important for specific DNA binding.

PMID- 30213936
TI  - Lithiophilic-lithiophobic gradient interfacial layer for a highly stable lithium
      metal anode.
AB  - The long-standing issue of lithium dendrite growth during repeated deposition or
      dissolution processes hinders the practical use of lithium-metal anodes for high
      energy density batteries. Here, we demonstrate a promising lithiophilic
      lithiophobic gradient interfacial layer strategy in which the bottom lithiophilic
      zinc oxide/carbon nanotube sublayer tightly anchors the whole layer onto the
      lithium foil, facilitating the formation of a stable solid electrolyte
      interphase, and prevents the formation of an intermediate mossy lithium corrosion
      layer. Together with the top lithiophobic carbon nanotube sublayer, this gradient
      interfacial layer can effectively suppress dendrite growth and ensure ultralong
      term stable lithium stripping/plating. This strategy is further demonstrated to
      provide substantially improved cycle performance in copper current collector, 10
      cm2 pouch cell and lithium-sulfur batteries, which, coupled with a simple
      fabrication process and wide applicability in various materials for lithium-metal
      protection, makes the lithiophilic-lithiophobic gradient interfacial layer a
      favored strategy for next-generation lithium-metal batteries.

PMID- 30213937
TI  - Finding any Waldo with zero-shot invariant and efficient visual search.
AB  - Searching for a target object in a cluttered scene constitutes a fundamental
      challenge in daily vision. Visual search must be selective enough to discriminate
      the target from distractors, invariant to changes in the appearance of the
      target, efficient to avoid exhaustive exploration of the image, and must
      generalize to locate novel target objects with zero-shot training. Previous work
      on visual search has focused on searching for perfect matches of a target after
      extensive category-specific training. Here, we show for the first time that
      humans can efficiently and invariantly search for natural objects in complex
      scenes. To gain insight into the mechanisms that guide visual search, we propose
      a biologically inspired computational model that can locate targets without
      exhaustive sampling and which can generalize to novel objects. The model provides
      an approximation to the mechanisms integrating bottom-up and top-down signals
      during search in natural scenes.

PMID- 30213938
TI  - Negatively charged nanoporous membrane for a dendrite-free alkaline zinc-based
      flow battery with long cycle life.
AB  - Alkaline zinc-based flow batteries are regarded to be among the best choices for
      electric energy storage. Nevertheless, application is challenged by the issue of
      zinc dendrite/accumulation. Here, we report a negatively charged nanoporous
      membrane for a dendrite-free alkaline zinc-based flow battery with long cycle
      life. Free of zinc dendrite/accumulation, stable performance is afforded for ~240
      cycles at current densities ranging from 80 to 160 mA cm-2 using the negatively
      charged nanoporous membrane. Furthermore, 8 h and 7 h plating/stripping processes
      at 40 mA cm-2 yield an average energy efficiency of 91.92% and an areal discharge
      capacity above 130 mAh cm-2. A peak power density of 1056 mW cm-2 is achieved at
      1040 mA cm-2. This study may provide an effective way to address the issue of
      zinc dendrite/accumulation for zinc-based batteries and accelerate the
      advancement of these batteries.

PMID- 30213939
TI  - Copper-catalyzed methylative difunctionalization of alkenes.
AB  - Trifluoromethylative difunctionalization and hydrofunctionalization of
      unactivated alkenes have been developed into powerful synthetic methodologies. On
      the other hand, methylative difunctionalization of olefins remains an unexplored
      research field. We report in this paper the Cu-catalyzed alkoxy methylation,
      azido methylation of alkenes using dicumyl peroxide (DCP), and di-tert-butyl
      peroxide (DTBP) as methyl sources. Using functionalized alkenes bearing a
      tethered nucleophile (alcohol, carboxylic acid, and sulfonamide), methylative
      cycloetherification, lactonization, and cycloamination processes are subsequently
      developed for the construction of important heterocycles such as 2,2
      disubstituted tetrahydrofurans, tetrahydropyrans, gamma-lactones, and
      pyrrolidines with concurrent generation of a quaternary carbon center. The
      results of control experiments suggest that the 1,2-alkoxy methylation of alkenes
      goes through a radical-cation crossover mechanism, whereas the 1,2-azido
      methylation proceeds via a radical addition and Cu-mediated azide transfer
      process.

PMID- 30213941
TI  - Spin dynamics of the block orbital-selective Mott phase.
AB  - Iron-based superconductors display a variety of magnetic phases originating in
      the competition between electronic, orbital, and spin degrees of freedom.
      Previous theoretical investigations of the multi-orbital Hubbard model in one
      dimension revealed the existence of an orbital-selective Mott phase (OSMP) with
      block spin order. Recent inelastic neutron scattering (INS) experiments on the
      BaFe2Se3 ladder compound confirmed the relevance of the block-OSMP. Moreover, the
      powder INS spectrum revealed an unexpected structure, containing both low-energy
      acoustic and high-energy optical modes. Here we present the theoretical
      prediction for the dynamical spin structure factor within a block-OSMP regime
      using the density-matrix renormalization-group method. In agreement with
      experiments, we find two dominant features: low-energy dispersive and high-energy
      dispersionless modes. We argue that the former represents the spin-wave-like
      dynamics of the block ferromagnetic islands, while the latter is attributed to a
      novel type of local on-site spin excitations controlled by the Hund coupling.

PMID- 30213940
TI  - SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to
      mediate Wntless sorting and Wnt secretion.
AB  - Wntless transports Wnt morphogens to the cell surface and is required for Wnt
      secretion and morphogenic gradients formation. Recycling of endocytosed Wntless
      requires the sorting nexin-3 (SNX3)-retromer-dependent endosome-to-Golgi
      transport pathway. Here we demonstrate the essential role of SNX3-retromer
      assembly for Wntless transport and report that SNX3 associates with an
      evolutionary conserved endosome-associated membrane re-modelling complex composed
      of MON2, DOPEY2 and the putative aminophospholipid translocase, ATP9A. In vivo
      suppression of Ce-mon-2, Ce-pad-1 or Ce-tat-5 (respective MON2, DOPEY2 and ATP9A
      orthologues) phenocopy a loss of SNX3-retromer function, leading to enhanced
      lysosomal degradation of Wntless and a Wnt phenotype. Perturbed Wnt signalling is
      also observed upon overexpression of an ATPase-inhibited TAT-5(E246Q) mutant,
      suggesting a role for phospholipid flippase activity during SNX3-retromer
      mediated Wntless sorting. Together, these findings provide in vitro and in vivo
      mechanistic details to describe SNX3-retromer-mediated transport during Wnt
      secretion and the formation of Wnt-morphogenic gradients.

PMID- 30213942
TI  - Age structure landscapes emerge from the equilibrium between aging and
      rejuvenation in bacterial populations.
AB  - The physiological asymmetry between daughters of a mother bacterium is produced
      by the inheritance of either old poles, carrying non-genetic damage, or newly
      synthesized poles. However, as bacteria display long-term growth stability
      leading to physiological immortality, there is controversy on whether asymmetry
      corresponds to aging. Here we show that deterministic age structure landscapes
      emerge from physiologically immortal bacterial lineages. Through single-cell
      microscopy and microfluidic techniques, we demonstrate that aging and
      rejuvenating bacterial lineages reach two distinct states of growth equilibria.
      These equilibria display stabilizing properties, which we quantified according to
      the compensatory trajectories of continuous lineages throughout generations.
      Finally, we show that the physiological asymmetry between aging and rejuvenating
      lineages produces complex age structure landscapes, resulting in a deterministic
      phenotypic heterogeneity that is neither an artifact of starvation nor a product
      of extrinsic damage. These findings indicate that physiological immortality and
      cellular aging can both be manifested in single celled organisms.

PMID- 30213943
TI  - Hepatorenal syndrome.
AB  - Hepatorenal syndrome (HRS) is a form of kidney function impairment that
      characteristically occurs in cirrhosis. Recent changes in terminology have led to
      acute HRS being referred to as acute kidney injury (AKI)-HRS and chronic HRS as
      chronic kidney disease (CKD)-HRS. AKI-HRS is characterized by a severe impairment
      of kidney function owing to vasoconstriction of the renal arteries in the absence
      of substantial abnormalities in kidney histology. Pathogenetic mechanisms involve
      disturbances in circulatory function due to a marked splanchnic arterial
      vasodilation, which triggers the activation of vasoconstrictor factors. An
      intense systemic inflammatory reaction that is characteristic of advanced
      cirrhosis may also be involved. The main triggering factors of AKI-HRS are
      bacterial infections, particularly spontaneous bacterial peritonitis. The
      diagnosis of AKI-HRS is a challenge because of a lack of specific diagnostic
      tools and mainly involves the differential diagnosis from other forms of AKI,
      particularly acute tubular necrosis. The prognosis of patients with AKI-HRS is
      poor, with a median survival of <=3 months. The ideal treatment for AKI-HRS is
      liver transplantation in patients without contraindications. Medical therapy
      consists of vasoconstrictor drugs to counteract splanchnic arterial vasodilation
      together with volume expansion with albumin. Effective measures to prevent AKI
      HRS include early identification and treatment of bacterial infections and the
      administration of albumin in patients with spontaneous bacterial peritonitis.

PMID- 30213944
TI  - Less absorbed solar energy and more internal heat for Jupiter.
AB  - The radiant energy budget and internal heat are fundamental properties of giant
      planets, but precise determination of these properties remains a challenge. Here,
      we report measurements of Jupiter's radiant energy budget and internal heat based
      on Cassini multi-instrument observations. Our findings reveal that Jupiter's Bond
      albedo and internal heat, 0.503 +/- 0.012 and 7.485 +/- 0.160 W m-2 respectively,
      are significantly larger than 0.343 +/- 0.032 and 5.444 +/- 0.425 Wm-2, the
      previous best estimates. The new results help constrain and improve the current
      evolutionary theories and models for Jupiter. Furthermore, the significant
      wavelength dependency of Jupiter's albedo implies that the radiant energy budgets
      and internal heat of the other giant planets in our solar system should be re
      examined. Finally, the data sets of Jupiter's characteristics of reflective solar
      spectral irradiance provide an observational basis for the models of giant
      exoplanets.

PMID- 30213945
TI  - A patient-centric analysis to identify key influences in allergic rhinitis
      management.
AB  - Allergic rhinitis (AR) is increasingly becoming a patient self-managed disease.
      Just under 70% of patients purchasing pharmacotherapy self-select their treatment
      with no health-care professional intervention often resulting in poor choices,
      leading to suboptimal management and increased burden of AR on the individual and
      the community. However, no decision is made without external, influencing forces.
      This study aims to determine the key influences driving patients' decision-making
      around AR management. To accomplish this aim, we utilised a social network theory
      framework to map the patient's AR network and identify the strength of the
      influences within this network. Adults who reported having AR were interviewed
      and completed an AR network map and AR severity and quality of life
      questionnaires. Forty one people with AR completed the study. The AR networks of
      the participants had a range of 1-11 influences (alters), with an average number
      of 4 and a median of 5. The larger the impact of AR on their quality of life, the
      greater the number of alters within their network. The three most commonly
      identified alters were, general practitioners, pharmacists and the participants'
      'own experience'. The strength of the influence of health-care professionals
      (HCPs) was varied. The proportion of HCPs within the AR network increased as the
      impact of AR on their quality of life increased. By mapping the AR network, this
      study demonstrated that there are multiple influences behind patient's decisions
      regarding AR management but the role of the HCP cannot be dismissed.

PMID- 30213946
TI  - A small molecule targeting myoferlin exerts promising anti-tumor effects on
      breast cancer.
AB  - Breast cancer is one of the most lethal cancers in women when it reaches the
      metastatic stage. Here, we screen a library of small molecules for inhibitors of
      breast cancer cell invasion, and use structure/activity relationship studies to
      develop a series of small molecules with improved activity. We find WJ460 as one
      of the lead compounds exerting anti-metastatic activity in the nanomolar range in
      breast cancer cells. Proteomic and biochemical studies identify myoferlin (MYOF)
      as the direct target of WJ460. In parallel, loss of MYOF or pharmacological
      inhibition of MYOF by WJ460 reduces breast cancer extravasation into the lung
      parenchyma in an experimental metastasis mouse model, which reveals an essential
      role of MYOF in breast cancer progression. Our findings suggest that MYOF can be
      explored as a molecular target in breast cancer metastasis and that targeting
      MYOF by WJ460 may be a promising therapeutic strategy in MYOF-driven cancers.

PMID- 30213947
TI  - Development of an antibody fragment that stabilizes GPCR/G-protein complexes.
AB  - Single-particle cryo-electron microscopy (cryo-EM) has recently enabled high
      resolution structure determination of numerous biological macromolecular
      complexes. Despite this progress, the application of high-resolution cryo-EM to G
      protein coupled receptors (GPCRs) in complex with heterotrimeric G proteins
      remains challenging, owning to both the relative small size and the limited
      stability of these assemblies. Here we describe the development of antibody
      fragments that bind and stabilize GPCR-G protein complexes for the application of
      high-resolution cryo-EM. One antibody in particular, mAb16, stabilizes GPCR/G
      protein complexes by recognizing an interface between Galpha and Gbetagamma
      subunits in the heterotrimer, and confers resistance to GTPgammaS-triggered
      dissociation. The unique recognition mode of this antibody makes it possible to
      transfer its binding and stabilizing effect to other G-protein subtypes through
      minimal protein engineering. This antibody fragment is thus a broadly applicable
      tool for structural studies of GPCR/G-protein complexes.

PMID- 30213948
TI  - METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or
      PPARdelta-dependent pathways in skeletal muscle of mice.
AB  - Physical activity has many beneficial effects on metabolic disorders, such as
      obesity, insulin resistance, and diabetes. Meteorin-like protein (METRNL), a
      novel secreted protein homologous to the neurotrophin Metrn, is induced after
      exercise in the skeletal muscle. Herein, we investigated the effects of METRNL on
      lipid-mediated inflammation and insulin resistance in skeletal muscle via AMP
      activated protein kinase (AMPK) or peroxisome proliferator-activated receptor
      delta (PPARdelta). Treatment with METRNL suppressed inflammatory markers, such as
      nuclear factor kappaB (NFkappaB) nuclear translocation, inhibitory kappaBalpha
      (IkappaBalpha) phosphorylation, interleukin-6 (IL-6) expression, and pro
      inflammatory cytokines (such as TNFalpha and MCP-1). METRNL treatment also
      attenuated the impaired insulin response both in palmitate-treated differentiated
      C2C12 cells and the skeletal muscle of high-fat diet (HFD)-fed mice. Furthermore,
      METRNL administration rescued glucose intolerance and reduced HFD-induced body
      weight gain in mice; however, METRNL did not affect calorie intake. METRNL
      treatment increased AMPK phosphorylation and PPARdelta expression both in
      differentiated C2C12 cells and mouse skeletal muscle. siRNA-mediated suppression
      of AMPK and PPARdelta abrogated the suppressive effects of METRNL on palmitate
      induced inflammation and insulin resistance. Moreover, METRNL augmented the mRNA
      expression of fatty acid oxidation-associated genes, such as carnitine
      palmitoyltransferase 1 (CPT1), acyl-CoA oxidase (ACO), and fatty acid binding
      protein 3 (FABP3). siRNAs for AMPK and PPARdelta reversed these changes. In the
      current study, we report for the first time that METRNL alleviates inflammation
      and insulin resistance and induces fatty acid oxidation through AMPK or PPARdelta
      dependent signaling in skeletal muscle.

PMID- 30213950
TI  - Extreme-ultraviolet high-harmonic generation in liquids.
AB  - High-harmonic generation (HHG) in gases has been the main enabling technology of
      attosecond science since its discovery. Recently, HHG from solids has been
      demonstrated, opening a lively area of research. In contrast, harmonic generation
      from liquids has so far remained restricted to low harmonics in the visible
      regime. Here, we report the observation and detailed characterization of extreme
      ultraviolet HHG from liquid water and several alcohols extending beyond 20 eV.
      This advance was enabled by the implementation of the recent liquid flat-microjet
      technology, which we show to facilitate the spatial separation of HHG from the
      bulk liquid and the surrounding gas phase. We observe striking differences
      between the HHG spectra of water and several alcohols. A comparison with a
      strongly-driven few-band model establishes the sensitivity of HHG to the
      electronic structure of liquids. Our results suggest liquid-phase high-harmonic
      spectroscopy as a new method for studying the electronic structure and ultrafast
      scattering processes in liquids.

PMID- 30213949
TI  - Converting organosulfur compounds to inorganic polysulfides against resistant
      bacterial infections.
AB  - The use of natural substance to ward off microbial infections has a long history.
      However, the large-scale production of natural extracts often reduces
      antibacterial potency, thus limiting practical applications. Here we present a
      strategy for converting natural organosulfur compounds into nano-iron sulfides
      that exhibit enhanced antibacterial activity. We show that compared to garlic
      derived organosulfur compounds nano-iron sulfides exhibit an over 500-fold
      increase in antibacterial efficacy to kill several pathogenic and drug-resistant
      bacteria. Furthermore, our analysis reveals that hydrogen polysulfanes released
      from nano-iron sulfides possess potent bactericidal activity and the release of
      polysulfanes can be accelerated by the enzyme-like activity of nano-iron
      sulfides. Finally, we demonstrate that topical applications of nano-iron sulfides
      can effectively disrupt pathogenic biofilms on human teeth and accelerate
      infected-wound healing. Together, our approach to convert organosulfur compounds
      into inorganic polysulfides potentially provides an antibacterial alternative to
      combat bacterial infections.

PMID- 30213951
TI  - Charge-tuneable biexciton complexes in monolayer WSe2.
AB  - Monolayer transition metal dichalcogenides have strong Coulomb-mediated many-body
      interactions. Theoretical studies have predicted the existence of numerous multi
      particle excitonic states. Two-particle excitons and three-particle trions have
      been identified by their optical signatures. However, more complex states such as
      biexcitons have been elusive due to limited spectral quality of the optical
      emission. Here, we report direct evidence of two biexciton complexes in monolayer
      tungsten diselenide: the four-particle neutral biexciton and the five-particle
      negatively charged biexciton. We distinguish these states by power-dependent
      photoluminescence and demonstrate full electrical switching between them. We
      determine the band states of the elementary particles comprising the biexcitons
      through magneto-optical spectroscopy. We also resolve a splitting of 2.5 meV for
      the neutral biexciton, which we attribute to the fine structure, providing
      reference for subsequent studies. Our results unveil the nature of multi-exciton
      complexes in transitionmetal dichalcogenides and offer direct routes towards
      deterministic control in many-body quantum phenomena.

PMID- 30213952
TI  - Postoperative seizure outcome and timing interval to start antiepileptic drug
      withdrawal: A retrospective observational study of non-neoplastic drug resistant
      epilepsy.
AB  - This study aimed to investigate the impact of timing interval to start AED
      withdraw (TIW) after surgery on the seizure outcome in non-neoplastic drug
      resistant epilepsy (DRE). TIW were divided into three groups (respectively,<1
      year, 1-<2 years, and >=2 years). The seizure outcome at the different time
      points after starting AED withdrawal were compared among three groups. Other
      factors that related to seizure recurrence and TIW were included into the
      multiple analysis to investigate the predictors of seizure-free. Altogether, 205
      patients were involved in the study. 102 individuals (50%) had seizure recurrence
      and 127 (62%) had seizure-free at the final follow up. 115 of them have attempted
      AED reduction and had not seizure recurrence before AED reduction. The rate of
      seizure-free had no significant difference among people with different TIW.
      Multiple analysis indicated that temporal surgery is a favorable predictor of
      seizure-free at the first year after starting AED withdrawal, and preoperative
      secondary generalized seizures is an unfavorable predictor of seizure-free at the
      final follow up. In patients with non-neoplastic DRE, TIW is not the mainly
      influence factor on seizure outcome, however, preoperative secondary generalized
      seizures and extra-temporal surgery are negatively associated with seizure-free.

PMID- 30213953
TI  - RNA-Seq Analysis of Spinal Cord Tissues from hPFN1G118V Transgenic Mouse Model of
      ALS at Pre-symptomatic and End-Stages of Disease.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that
      leads to the loss of motor neurons. The molecular mechanisms of motor neuron
      degeneration are largely unknown and there are currently no effective therapies
      to treat this disease. In this work, we report whole transcriptome profiling of
      spinal cords of mutant transgenic hPFN1G118V mice and their wildtype transgenic
      hPFN1WT controls at a pre-symptomatic stage and at the end-stage of disease.
      Analyses revealed that end-stage hPFN1G118V mice had 890 differentially expressed
      genes (747 up-regulated, 143 down-regulated) when compared to pre-symptomatic
      hPFN1G118V mice, and they had 836 differentially expressed genes (742 up
      regulated, 94 down-regulated) when compared to age-matched hPFN1WT controls. Pre
      symptomatic hPFN1G118V mice were not significantly different from age-matched
      hPFN1WT controls. Ingenuity Pathway Analysis identified inflammatory pathways
      significantly activated in end-stage hPFN1G118V samples, suggesting an excess of
      glial activation at end-stage disease, possibly due to an increase in glial
      composition within the spinal cord during disease progression. In conclusion, our
      RNA-Seq data identified molecules and pathways involved in the mechanisms of
      neurodegeneration that could potentially serve as therapeutic targets for ALS.

PMID- 30213955
TI  - Enhanced-contrast optical readout in ultrafast broadband Raman quantum memories.
AB  - The signal-to-noise contrast of the optical readout in broadband Raman quantum
      memories is analyzed as a function of the pulse widths and phase properties of
      tailored optical field waveforms used to write in and read out broadband photon
      wave packets. Based on this analysis, we quantify the tradeoff between the
      readout contrast and the speed of such memories. Off-resonance coherent four-wave
      mixing is shown to provide a source of noise photons, lowering the readout
      contrast in broadband Raman quantum memories. This noise cannot be suppressed by
      phase matching, but can be radically reduced with a suitable polarization
      arrangement and proper field-waveform tailoring.

PMID- 30213954
TI  - The Possible Role of Neurobeachin in Extinction of Contextual Fear Memory.
AB  - Established fear memory becomes vulnerable to disruption after memory retrieval
      and extinction; this labile state is critical for inhibiting the return of fear
      memory. However, the labile state has a very narrow time window after retrieval,
      and underlying molecular mechanisms are not well known. To that end, we isolated
      the hippocampus immediately after fear memory retrieval and performed proteomics.
      We identified Neurobeachin (NBEA), an autism-related regulator of synaptic
      protein trafficking, to be upregulated after contextual fear memory retrieval.
      NBEA protein expression was rapid and transient after fear memory retrieval at
      the synapse. Nbea mRNA was enriched at the synapses, and the rapid induction of
      NBEA expression was blocked by inhibition of the mammalian target of rapamycin
      (mTOR)-dependent signaling pathway. Mice with cornu ammonis 1 (CA1)-specific Nbea
      shRNA knockdown showed normal fear acquisition and contextual fear memory but
      impaired extinction, suggesting an important role of Nbea in fear memory
      extinction processes. Consistently, Nbea heterozygotes showed normal fear
      acquisition and fear memory recall but showed impairment in extinction. Our data
      suggest that NBEA is necessary either for induction of memory lability or for the
      physiological process of memory extinction.

PMID- 30213956
TI  - A quantitative analysis linking sea turtle mortality and plastic debris
      ingestion.
AB  - Plastic in the marine environment is a growing environmental issue. Sea turtles
      are at significant risk of ingesting plastic debris at all stages of their
      lifecycle with potentially lethal consequences. We tested the relationship
      between the amount of plastic a turtle has ingested and the likelihood of death,
      treating animals that died of known causes unrelated to plastic ingestion as a
      statistical control group. We utilized two datasets; one based on necropsies of
      246 sea turtles and a second using 706 records extracted from a national
      strandings database. Animals dying of known causes unrelated to plastic ingestion
      had less plastic in their gut than those that died of either indeterminate causes
      or due to plastic ingestion directly (e.g. via gut impaction and perforation). We
      found a 50% probability of mortality once an animal had 14 pieces of plastic in
      its gut. Our results provide the critical link between recent estimates of
      plastic ingestion and the population effects of this environmental threat.

PMID- 30213957
TI  - Recovery of horse fly populations in Louisiana marshes following the Deepwater
      Horizon oil spill.
AB  - The Deepwater Horizon oil spill in April 2010 had unprecedented impact on the
      Gulf of Mexico. We established the greenhead horse fly (Tabanus nigrovittatus
      Macquart) as a bioindicator of marsh health. This species is bound to coastal
      marshes, since its larvae develop as top invertebrate predators in the marsh
      soil. Immediately after the oil spill (2010-2011), populations of this horse fly
      declined in oiled areas of Louisiana marshes with significant impacts on genetic
      structure. In this follow-up study five years after the catastrophic event (2015
      2016), we now report signs of recovery of populations in formerly oiled areas.
      Fly numbers increased compared to previous counts. Previously detected genetic
      bottlenecks in oiled populations have disappeared. Migration into oiled areas
      began to replenish formerly depleted horse fly populations in impacted regions
      with populations from non-oiled areas as an important source of migrants.
      Parameters of family structure that had been impacted by the oil spill (number of
      breeding parents, effective population size, number of family clusters) rebounded
      to levels similar to or exceeding those in non-oiled control areas.

PMID- 30213958
TI  - Rapid functional genetics of the oligodendrocyte lineage using pluripotent stem
      cells.
AB  - Oligodendrocyte dysfunction underlies many neurological disorders, but rapid
      assessment of mutation-specific effects in these cells has been impractical. To
      enable functional genetics in oligodendrocytes, here we report a highly efficient
      method for generating oligodendrocytes and their progenitors from mouse embryonic
      and induced pluripotent stem cells, independent of mouse strain or mutational
      status. We demonstrate that this approach, when combined with genome engineering,
      provides a powerful platform for the expeditious study of genotype-phenotype
      relationships in oligodendrocytes.

PMID- 30213959
TI  - Advanced glycation end products accelerate calcification in VSMCs through HIF
      1alpha/PDK4 activation and suppress glucose metabolism.
AB  - Arterial media calcification is associated with diabetes mellitus. Previous
      studies have shown that advanced glycation end products (AGEs) are responsible
      for vascular smooth muscle cell (VSMC) calcification, but the underlying
      mechanisms remain unclear. Hypoxia-inducible factor-1alpha (HIF-1alpha), one of
      the major factors during hypoxia, and pyruvate dehydrogenase kinase 4 (PDK4), an
      important mitochondrial matrix enzyme in cellular metabolism shift, have been
      reported in VSMC calcification. The potential link among HIF-1alpha, PDK4, and
      AGEs-induced vascular calcification was investigated in this study. We observed
      that AGEs elevated HIF-1alpha and PDK4 expression levels in a dose-dependent
      manner and that maximal stimulation was attained at 24 h. Two important HIF
      1alpha-regulated genes, vascular endothelial growth factor A (VEGFA) and glucose
      transporter 1 (GLUT-1), were significantly increased after AGEs exposure.
      Stabilization or nuclear translocation of HIF-1alpha increased PDK4 expression.
      PDK4 inhibition attenuated AGEs-induced VSMC calcification, which was evaluated
      by measuring the calcium content, alkaline phosphatase (ALP) activity and runt
      related transcription factor 2 (RUNX2) expression levels and by Alizarin red S
      staining. In addition, the glucose consumption, lactate production, key enzymes
      of glucose metabolism and oxygen consumption rate (OCR) were decreased during
      AGEs-induced VSMC calcification. In conclusion, this study suggests that AGEs
      accelerate vascular calcification partly through the HIF-1alpha/PDK4 pathway and
      suppress glucose metabolism.

PMID- 30213960
TI  - Volume phase transition kinetics of smart N-n-propylacrylamide microgels studied
      by time-resolved pressure jump small angle neutron scattering.
AB  - The use of smart colloidal microgels for advanced applications critically depends
      on their response kinetics. We use pressure jump small angle neutron scattering
      with supreme time resolution to study the rapid volume phase transition kinetics
      of such microgels. Utilizing the pressure induced microphase separation inside
      the microgels we were able to resolve their collapse and swelling kinetics. While
      the collapse occurs on a time scale of 10 ms, the particle swelling turned out to
      be much faster. Photon correlation spectroscopy and static small angle neutron
      scattering unambiguously show, that the much slower collapse can be associated
      with the complex particle architecture exhibiting a loosely-crosslinked outer
      region and a denser inner core region. These insights into the kinetics of
      stimuli-responsive materials are of high relevance for their applications as nano
      actuators, sensors or drug carriers. Moreover, the used refined pressure jump
      small angle neutron scattering technique is of broad interest for soft matter
      studies.

PMID- 30213961
TI  - Polymeric Nitrogen A7 Layers Stabilized in the Confinement of a Multilayer BN
      Matrix at Ambient Conditions.
AB  - Polymeric nitrogen, as a potential high-energy-density material (HEDM), has
      attracted many theoretical calculations and predictions for its potential
      applications, such as energy storage, propellants and explosives. Searching for
      an effective method to stabilize polymeric nitrogen in ambient conditions of
      temperature and pressure has become a hot topic. Herein, we propose a new hybrid
      material where polymeric nitrogen layers are intercalated in a multilayer BN
      matrix forming a three-dimensional structure, by means of ab initio density
      functional theory. It is demonstrated polymeric nitrogen layers can be stable at
      ambient conditions and can release tremendous energy just above 500 K, more
      gentle and controllable. Further calculations reveal the new hybrid material
      exhibits a much smaller charge transfer than that of previous reports, which not
      only stabilizes polymeric nitrogen layer at ambient conditions, but also favours
      energy releasing at milder conditions. It is also very exciting that, the weight
      ratio of polymeric nitrogen in new material is up to 53.84%, approximately three
      times higher than previous one-dimensional hybrid materials. The energy density
      (5.4 KJ/g) also indicates it is a promising HEDMs candidate. Our findings provide
      a new insight into nitrogen-based HEDMs capture and storage.

PMID- 30213962
TI  - X-ray structure of full-length human RuvB-Like 2 - mechanistic insights into
      coupling between ATP binding and mechanical action.
AB  - RuvB-Like transcription factors function in cell cycle regulation, development
      and human disease, such as cancer and heart hyperplasia. The mechanisms that
      regulate adenosine triphosphate (ATP)-dependent activity, oligomerization and
      post-translational modifications in this family of enzymes are yet unknown. We
      present the first crystallographic structure of full-length human RuvBL2 which
      provides novel insights into its mechanistic action and biology. The ring-shaped
      hexameric RuvBL2 structure presented here resolves for the first time the mobile
      domain II of the human protein, which is responsible for protein-protein
      interactions and ATPase activity regulation. Structural analysis suggests how ATP
      binding may lead to domain II motion through interactions with conserved N
      terminal loop histidine residues. Furthermore, a comparison between hsRuvBL1 and
      2 shows differences in surface charge distribution that may account for
      previously described differences in regulation. Analytical ultracentrifugation
      and cryo electron microscopy analyses performed on hsRuvBL2 highlight an oligomer
      plasticity that possibly reflects different physiological conformations of the
      protein in the cell, as well as that single-stranded DNA (ssDNA) can promote the
      oligomerization of monomeric hsRuvBL2. Based on these findings, we propose a
      mechanism for ATP binding and domain II conformational change coupling.

PMID- 30213963
TI  - A machine learning approach to estimating preterm infants survival: development
      of the Preterm Infants Survival Assessment (PISA) predictor.
AB  - Estimation of mortality risk of very preterm neonates is carried out in clinical
      and research settings. We aimed at elaborating a prediction tool using machine
      learning methods. We developed models on a cohort of 23747 neonates <30 weeks
      gestational age, or <1501 g birth weight, enrolled in the Italian Neonatal
      Network in 2008-2014 (development set), using 12 easily collected perinatal
      variables. We used a cohort from 2015-2016 (N = 5810) as a test set. Among
      several machine learning methods we chose artificial Neural Networks (NN). The
      resulting predictor was compared with logistic regression models. In the test
      cohort, NN had a slightly better discrimination than logistic regression (P <
      0.002). The differences were greater in subgroups of neonates (at various
      gestational age or birth weight intervals, singletons). Using a cutoff of death
      probability of 0.5, logistic regression misclassified 67/5810 neonates (1.2
      percent) more than NN. In conclusion our study - the largest published so far -
      shows that even in this very simplified scenario, using only limited information
      available up to 5 minutes after birth, a NN approach had a small but significant
      advantage over current approaches. The software implementing the predictor is
      made freely available to the community.

PMID- 30213964
TI  - Artificial Shape Perception Retina Network Based on Tunable Memristive Neurons.
AB  - Retina shows an extremely high signal processing efficiency because of its
      specific signal processing strategy which called computing in sensor. In retina,
      photoreceptor cells encode light signals into spikes and ganglion cells finish
      the shape perception process. In order to realize the neuromorphic vision sensor,
      the one-transistor-one-memristor (1T1M) structure which formed by one memristor
      and one MOSFET in serial is used to construct photoreceptor cell and ganglion
      cell. The voltage changes between two terminals of memristor and MOSFET can mimic
      the changes of membrane potential caused by spikes and illumination respectively.
      In this paper, the tunable memristive neurons with 1T1M structures are built.
      According to the concept of receptive field of ganglion cells (GCs) in the
      retina, the artificial shape perception retina network is constructed with these
      memristive neurons. The final results show that the artificial retina can extract
      shape information from the image and transfer it into spike frequency realizing
      the function of computing in sensor.

PMID- 30213966
TI  - The Atlantic salmon (Salmo salar) antimicrobial peptide cathelicidin-2 is a
      molecular host-associated cue for the salmon louse (Lepeophtheirus salmonis).
AB  - Chemical signals are a key element of host-parasite interactions. In marine
      ecosystems, obligate ectoparasites, such as sea lice, use chemical cues and other
      sensory signals to increase the probability of encountering a host and to
      identify appropriate hosts on which they depend to complete their life cycle. The
      chemical compounds that underlie host identification by the sea lice are not
      fully described or characterized. Here, we report a novel compound - the Atlantic
      salmon (Salmo salar) antimicrobial peptide cathelicidin-2 (Cath-2) - that acts as
      an activation cue for the marine parasitic copepod Lepeophtheirus salmonis. L.
      salmonis were exposed to 0, 7, 70 and 700 ppb of Cath-2 and neural activity,
      swimming behaviour and gene expression profiles of animals in response to the
      peptide were evaluated. The neurophysiological, behavioural and transcriptomic
      results were consistent: L. salmonis detects Cath-2 as a water-soluble peptide
      released from the skin of salmon, triggering chemosensory neural activity
      associated with altered swimming behaviour of copepodids exposed to the peptide,
      and chemosensory-related genes were up-regulated in copepodids exposed to the
      peptide. L. salmonis are activated by Cath-2, indicating a tight link between
      this peptide and the salmon louse chemosensory system.

PMID- 30213965
TI  - Critical steps in clinical shotgun metagenomics for the concomitant detection and
      typing of microbial pathogens.
AB  - High throughput sequencing has been proposed as a one-stop solution for
      diagnostics and molecular typing directly from patient samples, allowing timely
      and appropriate implementation of measures for treatment, infection prevention
      and control. However, it is unclear how the variety of available methods impacts
      the end results. We applied shotgun metagenomics on diverse types of patient
      samples using three different methods to deplete human DNA prior to DNA
      extraction. Libraries were prepared and sequenced with Illumina chemistry. Data
      was analyzed using methods likely to be available in clinical microbiology
      laboratories using genomics. The results of microbial identification were
      compared to standard culture-based microbiological methods. On average, 75% of
      the reads corresponded to human DNA, being a major determinant in the analysis
      outcome. None of the kits was clearly superior suggesting that the initial ratio
      between host and microbial DNA or other sample characteristics were the major
      determinants of the proportion of microbial reads. Most pathogens identified by
      culture were also identified through metagenomics, but substantial differences
      were noted between the taxonomic classification tools. In two cases the high
      number of human reads resulted in insufficient sequencing depth of bacterial DNA
      for identification. In three samples, we could infer the probable multilocus
      sequence type of the most abundant species. The tools and databases used for
      taxonomic classification and antimicrobial resistance identification had a key
      impact on the results, recommending that efforts need to be aimed at
      standardization of the analysis methods if metagenomics is to be used routinely
      in clinical microbiology.

PMID- 30213967
TI  - Global establishment threat from a major forest pest via international shipping:
      Lymantria dispar.
AB  - The global shipping network is widely recognised as a pathway for vectoring
      invasive species. One species of particular concern is Lymantria dispar (gypsy
      moth). Two subspecies, L. d. asiatica and L. d. japonica (herein referred to as
      Asian Gypsy Moth - AGM) are of considerable concern as ships arriving to a number
      of countries have been found carrying AGM egg masses. However, ships carrying AGM
      eggs can only threaten a country at ports located in a climatically suitable
      region. We present a CLIMEX model of climate suitability and combine this with
      international shipping to estimate the global threat from AGM. We find that for
      the USA more than half of international ships (approximately 18,000 ships) arrive
      to climatically suitable ports. Other countries with a large number of ships
      arriving to ports with suitable climates include Canada and Brazil. This is the
      first global analysis of the invasion threat from AGM, and we recommend countries
      focus AGM-inspection programs towards ships arriving at ports found within
      climatically suitable regions.

PMID- 30213968
TI  - Optogenetic stimulation of complex spatio-temporal activity patterns by acousto
      optic light steering probes cerebellar granular layer integrative properties.
AB  - Optogenetics provides tools to control afferent activity in brain microcircuits.
      However, this requires optical methods that can evoke asynchronous and
      coordinated activity within neuronal ensembles in a spatio-temporally precise
      way. Here we describe a light patterning method, which combines MHz acousto-optic
      beam steering and adjustable low numerical aperture Gaussian beams, to achieve
      fast 2D targeting in scattering tissue. Using mossy fiber afferents to the
      cerebellar cortex as a testbed, we demonstrate single fiber optogenetic
      stimulation with micron-scale lateral resolution, >100 um depth-penetration and
      0.1 ms spiking precision. Protracted spatio-temporal patterns of light delivered
      by our illumination system evoked sustained asynchronous mossy fiber activity
      with excellent repeatability. Combining optical and electrical stimulations, we
      show that the cerebellar granular layer performs nonlinear integration, whereby
      sustained mossy fiber activity provides a permissive context for the transmission
      of salient inputs, enriching combinatorial views on mossy fiber pattern
      separation.

PMID- 30213969
TI  - DNA hypermethylation and differential gene expression associated with Klinefelter
      syndrome.
AB  - Klinefelter syndrome (KS) has a prevalence ranging from 85 to 250 per 100.000
      newborn boys making it the most frequent sex chromosome aneuploidy in the general
      population. The molecular basis for the phenotypic traits and morbidity in KS are
      not clarified. We performed genome-wide DNA methylation profiling of leucocytes
      from peripheral blood samples from 67 KS patients, 67 male controls and 33 female
      controls, in addition to genome-wide RNA-sequencing profiling in a subset of 9 KS
      patients, 9 control males and 13 female controls. Characterization of the
      methylome as well as the transcriptome of both coding and non-coding genes
      identified a unique epigenetic and genetic landscape of both autosomal
      chromosomes as well as the X chromosome in KS. A subset of genes show significant
      correlation between methylation values and expression values. Gene set enrichment
      analysis of differentially methylated positions yielded terms associated with
      well-known comorbidities seen in KS. In addition, differentially expressed genes
      revealed enrichment for genes involved in the immune system, wnt-signaling
      pathway and neuron development. Based on our data we point towards new candidate
      genes, which may be implicated in the phenotype and further point towards non
      coding genes, which may be involved in X chromosome inactivation in KS.

PMID- 30213971
TI  - Replacement of the L-iduronic acid unit of the anticoagulant pentasaccharide
      idraparinux by a 6-deoxy-L-talopyranose - Synthesis and conformational analysis.
AB  - One critical part of the synthesis of heparinoid anticoagulants is the creation
      of the L-iduronic acid building block featured with unique conformational
      plasticity which is crucial for the anticoagulant activity. Herein, we studied
      whether a much more easily synthesizable sugar, the 6-deoxy-L-talose, built in a
      heparinoid oligosaccharide, could show a similar conformational plasticity,
      thereby can be a potential substituent of the L-idose. Three pentasaccharides
      related to the synthetic anticoagulant pentasaccharide idraparinux were prepared,
      in which the L-iduronate was replaced by a 6-deoxy-L-talopyranoside unit. The
      talo-configured building block was formed by C4 epimerisation of the commercially
      available L-rhamnose with high efficacy at both the monosaccharide and the
      disaccharide level. The detailed conformational analysis of these new
      derivatives, differing only in their methylation pattern, was performed and the
      conformationally relevant NMR parameters, such as proton-proton coupling
      constants and interproton distances were compared to the corresponding ones
      measured in idraparinux. The lack of anticoagulant activity of these novel
      heparin analogues could be explained by the biologically not favorable 1C4 chair
      conformation of their 6-deoxy-L-talopyranoside residues.

PMID- 30213970
TI  - Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.
AB  - Transcriptomic analysis showed that the central circadian pathway genes had
      significantly altered expression in fracture calluses from mice fed a low
      phosphate diet. This led us to hypothesize that phosphate deficiency altered the
      circadian cycle in peripheral tissues. Analysis of the expression of the central
      clock genes over a 24-36 hour period in multiple peripheral tissues including
      fracture callus, proximal tibia growth plate and cardiac tissues after 12 days on
      a low phosphate diet showed higher levels of gene expression in the
      hypophosphatemia groups (p < 0.001) and a 3 to 6 hour elongation of the circadian
      cycle. A comparative analysis of the callus tissue transcriptome genes that were
      differentially regulated by hypophosphatemia with published data for the genes in
      bone that are diurnally regulated identified 1879 genes with overlapping
      differential regulation, which were shown by ontology assessment to be associated
      with oxidative metabolism and apoptosis. Network analysis of the central
      circadian pathway genes linked their expression to the up regulated expression of
      the histone methyltransferase gene EZH2, a gene that when mutated in both humans
      and mice controls overall skeletal growth. These data suggest that phosphate is
      an essential metabolite that controls circadian function in both skeletal and non
      skeletal peripheral tissues and associates its levels with the overall oxidative
      metabolism and skeletal growth of animals.

PMID- 30213972
TI  - Link between carrot leaf secondary metabolites and resistance to Alternaria
      dauci.
AB  - Alternaria Leaf Blight (ALB), caused by the fungus Alternaria dauci, is the most
      damaging foliar disease affecting carrots (Daucus carota). In order to identify
      compounds potentially linked to the resistance to A. dauci, we have used a
      combination of targeted and non-targeted metabolomics to compare the leaf
      metabolome of four carrot genotypes with different resistance levels. Targeted
      analyses were focused on terpene volatiles, while total leaf methanolic extracts
      were subjected to non-targeted analyses using liquid chromatography couple to
      high-resolution mass spectrometry. Differences in the accumulation of major
      metabolites were highlighted among genotypes and some of these metabolites were
      identified as potentially involved in resistance or susceptibility. A bulk
      segregant analysis on F3 progenies obtained from a cross between one of the
      resistant genotypes and a susceptible one, confirmed or refuted the hypothesis
      that the metabolites differentially accumulated by these two parents could be
      linked to resistance.

PMID- 30213973
TI  - Investigating the genetic profile of dopaminergic neurons in the VTA in response
      to perinatal nicotine exposure using mRNA-miRNA analyses.
AB  - Maternal smoking during pregnancy is associated with an increased risk of
      developmental, behavioral, and cognitive deficits. Nicotine, the primary
      addictive component in tobacco, has been shown to modulate changes in gene
      expression when exposure occurs during neurodevelopment. The ventral tegmental
      area (VTA) is believed to be central to the mechanism of addiction because of its
      involvement in the reward pathway. The purpose of this study was to build a
      genetic profile for dopamine (DA) neurons in the VTA and investigate the
      disruptions to the molecular pathways after perinatal nicotine exposure.
      Initially, we isolated the VTA from rat pups treated perinatally with either
      nicotine or saline (control) and collected DA neurons using fluorescent-activated
      cell sorting. Using microarray analysis, we profiled the differential expression
      of mRNAs and microRNAs from DA neurons in the VTA in order to explore potential
      points of regulation and enriched pathways following perinatal nicotine exposure.
      Furthermore, mechanisms of miRNA-mediated post-transcriptional regulation were
      investigated using predicted and validated miRNA-gene targets in order to
      demonstrate the role of miRNAs in the mesocorticolimbic DA pathway. This study
      provides insight into the genetic profile as well as biological pathways of DA
      neurons in the VTA of rats following perinatal nicotine exposure.

PMID- 30213974
TI  - Geobiology reveals how human kidney stones dissolve in vivo.
AB  - More than 10% of the global human population is now afflicted with kidney stones,
      which are commonly associated with other significant health problems including
      diabetes, hypertension and obesity. Nearly 70% of these stones are primarily
      composed of calcium oxalate, a mineral previously assumed to be effectively
      insoluble within the kidney. This has limited currently available treatment
      options to painful passage and/or invasive surgical procedures. We analyze kidney
      stone thin sections with a combination of optical techniques, which include
      bright field, polarization, confocal and super-resolution nanometer-scale auto
      fluorescence microscopy. Here we demonstrate using interdisciplinary geology and
      biology (geobiology) approaches that calcium oxalate stones undergo multiple
      events of dissolution as they crystallize and grow within the kidney. These
      observations open a fundamentally new paradigm for clinical approaches that
      include in vivo stone dissolution and identify high-frequency layering of organic
      matter and minerals as a template for biomineralization in natural and engineered
      settings.

PMID- 30213975
TI  - Copper mediated amyloid-beta binding to Transthyretin.
AB  - Transthyretin (TTR), a homotetrameric protein that transports thyroxine and
      retinol both in plasma and in cerebrospinal (CSF) fluid provides a natural
      protective response against Alzheimer's disease (AD), modulates amyloid-beta
      (Abeta) deposition by direct interaction and co-localizes with Abeta in plaques.
      TTR levels are lower in the CSF of AD patients. Zn2+, Mn2+ and Fe2+ transform TTR
      into a protease able to cleave Abeta. To explain these activities, monomer
      dissociation or conformational changes have been suggested. Here, we report that
      when TTR crystals are exposed to copper or iron salts, the tetramer undergoes a
      significant conformational change that alters the dimer-dimer interface and
      rearranges residues implicated in TTR's ability to neutralize Abeta. We also
      describe the conformational changes in TTR upon the binding of the various metal
      ions. Furthermore, using bio-layer interferometry (BLI) with immobilized Abeta(1
      28), we observe the binding of TTR only in the presence of copper. Such Cu2+
      dependent binding suggests a recognition mechanism whereby Cu2+ modulates both
      the TTR conformation, induces a complementary Abeta structure and may participate
      in the interaction. Cu2+-soaked TTR crystals show a conformation different from
      that induced by Fe2+, and intriguingly, TTR crystals grown in presence of Abeta(1
      28) show different positions for the copper sites from those grown its absence.

PMID- 30213976
TI  - Biexcitons in monolayer transition metal dichalcogenides tuned by magnetic
      fields.
AB  - We present time-integrated four-wave mixing measurements on monolayer MoSe2 in
      magnetic fields up to 25 T. The experimental data together with time-dependent
      density function theory calculations provide interesting insights into the
      biexciton formation and dynamics. In the presence of magnetic fields the
      coherence at negative and positive time delays is dominated by intervalley
      biexcitons. We demonstrate that magnetic fields can serve as a control to enhance
      the biexciton formation and help search for more exotic states of matter,
      including the creation of multiple exciton complexes and excitonic condensates.

PMID- 30213977
TI  - Highly transparent light emitting diodes on graphene encapsulated Cu nanowires
      network.
AB  - The internal quantum efficiency of blue LEDs is almost close to the limit,
      therefore, advanced transparent electrode has been long explored for gaining high
      external quantum efficiency. However, work function mismatch at electrode
      semiconductor interface remains the fundamental difficulty in obtaining low
      resistance ohmic contact. Here, we demonstrate the gas phase encapsulation of
      graphene layer on superfine Cu nanowires network by chemical vapor deposition for
      highly transparent LEDs. The fast encapsulation of graphene shell layer on Cu
      nanowires achieves high optoelectronic performance (33 Omega/sq @ 95% T), broad
      transparency range (200~3000 nm) and strong antioxidant stability. A novel
      phenomenon of scattered-point contact is revealed at the Cu nanowires/GaN
      interface. Point discharge effect is found to produce locally high injection
      current through contact points, which can effectively overcome Schottky barrier
      and form ohmic contact. The transparent LED on Cu@graphene nanowire network is
      successfully lighted with bright blue emission.

PMID- 30213978
TI  - Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular
      Dynamics Simulations.
AB  - Cannabinoid receptor 1 (CB1) is a promising therapeutic target for a variety of
      disorders. Distinct efficacy profiles showed different therapeutic effects on CB1
      dependent on three classes of ligands: agonists, antagonists, and inverse
      agonists. To discriminate the distinct efficacy profiles of the ligands, we
      carried out molecular dynamics (MD) simulations to identify the dynamic behaviors
      of inactive and active conformations of CB1 structures with the ligands. In
      addition, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method
      was applied to analyze the binding free energy decompositions of the CB1-ligand
      complexes. With these two methods, we found the possibility that the three
      classes of ligands can be discriminated. Our findings shed light on the
      understanding of different efficacy profiles of ligands by analyzing the
      structural behaviors of intact CB1 structures and the binding energies of
      ligands, thereby yielding insights that are useful for the design of new potent
      CB1 drugs.

PMID- 30213979
TI  - Morroniside regulates hair growth and cycle transition via activation of the
      Wnt/beta-catenin signaling pathway.
AB  - Hair loss is characterized by a shortened hair anagen phase and hair follicles
      (HF) miniaturization. Morroniside is the most abundant iridoid glycoside
      extracted from Cornus officinalis and has various bioactivities in different cell
      functions and tissue regeneration. In this study, we investigated the effects and
      the underlying mechanism of morroniside on hair growth and regulation of HF cycle
      transition. Morroniside treatment significantly enhanced outer root sheath cell
      (ORSC) proliferation and migration in vitro. Additionally, morroniside
      upregulated Wnt10b, beta-catenin and lef1. The enhanced ORSC proliferation and
      migration due to morroniside treatment were partly rescued by a Wnt/beta-catenin
      signaling inhibitor, DKK1. Furthermore, in a hair-induced mouse model,
      morroniside injection accelerated the onset of anagen and delayed HF catagen, as
      shown by histological examination. Immunohistochemical analyses revealed that
      Wnt/beta-catenin signaling pathway expression was upregulated in the HFs. These
      findings suggest that morroniside regulates HF growth and development partly
      through the Wnt/beta-catenin signaling pathway and may be a potential treatment
      for hair loss.

PMID- 30213980
TI  - G2Vec: Distributed gene representations for identification of cancer prognostic
      genes.
AB  - Identification of cancer prognostic genes is important in that it can lead to
      accurate outcome prediction and better therapeutic trials for cancer patients.
      Many computational approaches have been proposed to achieve this goal; however,
      there is room for improvement. Recent developments in deep learning techniques
      can aid in the identification of better prognostic genes and more accurate
      outcome prediction, but one of the main problems in the adoption of deep learning
      for this purpose is that data from cancer patients have too many dimensions,
      while the number of samples is relatively small. In this study, we propose a
      novel network-based deep learning method to identify prognostic gene signatures
      via distributed gene representations generated by G2Vec, which is a modified
      Word2Vec model originally used for natural language processing. We applied the
      proposed method to five cancer types including liver cancer and showed that G2Vec
      outperformed extant feature selection methods, especially for small number of
      samples. Moreover, biomarkers identified by G2Vec was useful to find significant
      prognostic gene modules associated with hepatocellular carcinoma.

PMID- 30213981
TI  - Effects on 24-hour blood pressure variability of ace-inhibition and calcium
      channel blockade as monotherapy or in combination.
AB  - Cardiovascular events in hypertensives are associated with elevated average blood
      pressure (BP) and higher short-term BP variability (V), but little is known on
      treatment effects on BPV and on how to assess changes in short-term BPV. Aim of
      our study was to address the methodology of short-term BPV assessment and its
      reduction by Lercanidipine (L) or Enalapril (E) and their combination, through
      analysis of 24-hour ambulatory BP recordings from two studies including subjects
      of different age. Study-1: 64 middle-age hypertensives (52.9 +/- 9.5 yrs)
      received L and E s.i.d. at 10 mg (L10, E10) or 20 mg doses (L20, E20) for 8
      weeks. Study-2: 66 elderly hypertensives (65.5 +/- 4.7 yrs) received placebo,
      L10, E20 and L10 + E20 s.i.d. for 4 weeks. In middle-age subjects, both L and E
      decreased mean BP and, at the highest dose, also short-term BPV. In elderly
      subjects, L10 alone or in combination with E20 reduced BPV. Treatment-induced
      reductions in BP levels and BPV were uncorrelated. Different methods for short
      term BPV assessment did not always provide superimposable results in the elderly.
      Our study supports a better reduction of BPV by L in the elderly and by E + L
      combination at any age, suggesting BPV reduction to be independent from reduction
      in average BP.

PMID- 30213982
TI  - Fluid absorption by skin tissue during intradermal injections through hollow
      microneedles.
AB  - Hollow microneedles are an emerging technology for delivering drugs and
      therapeutics, such as vaccines and insulin, into the skin. Although the benefits
      of intradermal drug delivery have been known for decades, our understanding of
      fluid absorption by skin tissue has been limited due to the difficulties in
      imaging a highly scattering biological material such as skin. Here, we report the
      first real-time imaging of skin tissue at the microscale during intradermal
      injections through hollow microneedles, using optical coherence tomography. We
      show that skin tissue behaves like a deformable porous medium and absorbs fluid
      by locally expanding rather than rupturing to form a single fluid filled cavity.
      We measure the strain distribution in a cross section of the tissue to quantify
      local tissue deformation, and find that the amount of volumetric expansion of the
      tissue corresponds closely to the volume of fluid injected. Mechanically
      restricting tissue expansion limits fluid absorption into the tissue. Our
      experimental findings can provide insights to optimize the delivery of drugs into
      skin for different therapeutic applications, and to better model fluid flow into
      biological tissue.

PMID- 30213983
TI  - Etoposide-resistance in a neuroblastoma model cell line is associated with
      13q14.3 mono-allelic deletion and miRNA-15a/16-1 down-regulation.
AB  - Drug resistance is the major obstacle in successfully treating high-risk
      neuroblastoma. The aim of this study was to investigate the basis of etoposide
      resistance in neuroblastoma. To this end, a MYCN-amplified neuroblastoma cell
      line (HTLA-230) was treated with increasing etoposide concentrations and an
      etoposide-resistant cell line (HTLA-ER) was obtained. HTLA-ER cells, following
      etoposide exposure, evaded apoptosis by altering Bax/Bcl2 ratio. While both cell
      populations shared a homozygous TP53 mutation encoding a partially-functioning
      protein, a mono-allelic deletion of 13q14.3 locus, where the P53 inducible miRNAs
      15a/16-1 are located, and the consequent miRNA down-regulation were detected only
      in HTLA-ER cells. This event correlated with BMI-1 oncoprotein up-regulation
      which caused a decrease in p16 tumor suppressor content and a metabolic
      adaptation of HTLA-ER cells. These results, taken collectively, highlight the
      role of miRNAs 15a/16-1 as markers of chemoresistance.

PMID- 30213984
TI  - Sertraline, chlorprothixene, and chlorpromazine characteristically interact with
      the REST-binding site of the corepressor mSin3, showing medulloblastoma cell
      growth inhibitory activities.
AB  - Dysregulation of repressor-element 1 silencing transcription factor REST/NRSF is
      related to several neuropathies, including medulloblastoma, glioblastoma,
      Huntington's disease, and neuropathic pain. Inhibitors of the interaction between
      the N-terminal repressor domain of REST/NRSF and the PAH1 domain of its
      corepressor mSin3 may ameliorate such neuropathies. In-silico screening based on
      the complex structure of REST/NRSF and mSin3 PAH1 yielded 52 active compounds,
      including approved neuropathic drugs. We investigated their binding affinity to
      PAH1 by NMR, and their inhibitory activity toward medulloblastoma cell growth.
      Interestingly, three antidepressant and antipsychotic medicines, sertraline,
      chlorprothixene, and chlorpromazine, were found to strongly bind to PAH1.
      Multivariate analysis based on NMR chemical shift changes in PAH1 residues
      induced by ligand binding was used to identify compound characteristics
      associated with cell growth inhibition. Active compounds showed a new chemo-type
      for inhibitors of the REST/NRSF-mSin3 interaction, raising the possibility of new
      therapies for neuropathies caused by dysregulation of REST/NRSF.

PMID- 30213985
TI  - Method for immobilization of living and synthetic cells for high-resolution
      imaging and single-particle tracking.
AB  - Super-resolution imaging and single-particle tracking require cells to be
      immobile as any movement reduces the resolution of the measurements. Here, we
      present a method based on APTES-glutaraldehyde coating of glass surfaces to
      immobilize cells without compromising their growth. Our method of immobilization
      is compatible with Saccharomyces cerevisiae, Escherichia coli, and synthetic
      cells (here, giant-unilamellar vesicles). The method introduces minimal
      background fluorescence and is suitable for imaging of single particles at high
      resolution. With S. cerevisiae we benchmarked the method against the commonly
      used concanavalin A approach. We show by total internal reflection fluorescence
      microscopy that modifying surfaces with ConA introduces artifacts close to the
      glass surface, which are not present when immobilizing with the APTES
      glutaraldehyde method. We demonstrate validity of the method by measuring the
      diffusion of membrane proteins in yeast with single-particle tracking and of
      lipids in giant-unilamellar vesicles with fluorescence recovery after
      photobleaching. Importantly, the physical properties and shape of the fragile
      GUVs are not affected upon binding to APTES-glutaraldehyde coated glass. The
      APTES-glutaraldehyde is a generic method of immobilization that should work with
      any cell or synthetic system that has primary amines on the surface.

PMID- 30213986
TI  - Association of circulating calprotectin with lipid profile in axial
      spondyloarthritis.
AB  - Calprotectin (CPT) is released during inflammation, also in the context of
      atherosclerosis. The link between CPT and the atherosclerotic process was
      evaluated in several diseases. However, studies in axial spondyloarthritis
      (axSpA), associated with a high incidence of subclinical atherosclerosis, are
      scarce. Therefore, we assessed the association of CPT with subclinical
      atherosclerosis and metabolic risk factors in axSpA. CPT serum levels were
      measured by enzyme-linked immunosorbent assay in 163 axSpA patients and 63
      controls. Subclinical atherosclerosis was determined in patients by carotid
      ultrasonography (assessing the presence/absence of carotid plaques and carotid
      intima-media thickness [cIMT]). Data on inflammation, disease activity, lipid
      profile and treatment were collected to evaluate its relationship with CPT. axSpA
      patients evidenced lower CPT levels than controls. CPT showed no association with
      plaques or cIMT in axSpA. CPT and HDL-cholesterol negatively correlated, while a
      positive association of CPT with the atherogenic index was disclosed.
      Additionally, axSpA patients with C-reactive protein values at diagnosis higher
      than 3 mg/L displayed higher CPT levels. Our study shows no relationship between
      CPT and markers of subclinical atherosclerosis in axSpA. Nevertheless, it
      demonstrates an association of CPT with adverse lipid profiles and inflammatory
      biomarkers, which could further influence on the development of atherosclerosis.

PMID- 30213988
TI  - A novel method for detection of camellia oil adulteration based on time-resolved
      emission fluorescence.
AB  - In this study, time-resolved emission fluorescence (TRES) combined with
      chemometrics was developed and employed for adulteration analysis of camellia
      oil. TRES was first decomposed by parallel factors analysis (PARAFAC). Next, an
      artificial neural network (ANN) model was built for the adulteration analysis. A
      linear range of 5-50%, a limit of detection (LOD) of 3% and root mean square
      error of prediction (RMSEP) values lower than 3% were achieved. Compared with the
      steady-state measurement, easy access to the information from fluorophores of low
      concentration was shown to be an intrinsic advantage of the time-resolved
      measurement; this advantageous characteristic was helpful for optimizing
      adulteration analysis. It was demonstrated that TRES combined with chemometrics
      was a simple, rapid and non-intrusive method for adulteration analysis of
      vegetable oil.

PMID- 30213987
TI  - A comprehensive manually-curated compendium of bovine transcription factors.
AB  - Transcription factors (TFs) are pivotal regulatory proteins that control gene
      expression in a context-dependent and tissue-specific manner. In contrast to
      human, where comprehensive curated TF collections exist, bovine TFs are only
      rudimentary recorded and characterized. In this article, we present a manually
      curated compendium of 865 sequence-specific DNA-binding bovines TFs, which we
      analyzed for domain family distribution, evolutionary conservation, and tissue
      specific expression. In addition, we provide a list of putative transcription
      cofactors derived from known interactions with the identified TFs. Since there is
      a general lack of knowledge concerning the regulation of gene expression in
      cattle, the curated list of TF should provide a basis for an improved
      comprehension of regulatory mechanisms that are specific to the species.

PMID- 30213990
TI  - Nitinol powders generate from Plasma Rotation Electrode Process provide clean
      powder for biomedical devices used with suitable size, spheroid surface and pure
      composition.
AB  - The nickel-titanium alloy (57Ni-43Ti in wt%) was atomized by the plasma rotating
      electrode process (PREP). The PREP parameters such as plasma arc current,
      rotating electrode speed with corresponding PREP powder size range in weight
      percentage analysis, powder morphology and biocapability of cells were studied by
      scanning electron microscopies, Inductively Coupled Plasma and X-ray diffraction
      techniques. From the electrode of the produced powders, the composition has no
      obviously changes. Weight percentage up to 31.8% of the range under 300 MUm while
      the rotation electrode speed increase to 12k rpm. Spherical and flat with smooth
      surface were observed in different size range. Brittle phase was not observed of
      XRD data. The nitinol powder has high biocapability with cells showed no
      cytotoxicity and well cell adhesion in the in vivo assay.

PMID- 30213989
TI  - One-pot synthesis of graphene- cobalt hydroxide composite nanosheets (Co/G NSs)
      for electrocatalytic water oxidation.
AB  - We report a one-pot method for the preparation of graphene-cobalt hydroxide
      nanosheets (Co/G NSs) and their use as an effective elelctrocatalyst for water
      oxidation. Mechanical exfoliation of graphite via sonication produced graphene
      sheets, which were stabilized by the surface adsorption of a cationic surfactant
      (CTAB). In a subsequent step, varying amount of a cobalt complex [sodium
      hexanitrocobaltate(III)] was added which selectively bound with the positively
      charged head of surfactant. In the last step, cobalt complex was reduced with
      sodium borohydride to obtain Co/G NSs catalyst. The catalyst showed lower
      overpotential (280 mV) as compared to benchmark catalysts and decent stability
      and turnover frequency (TOF: 0.089 s-1) for oxygen evolution reaction (OER).

PMID- 30213991
TI  - Efficient identification of somatic mutations in acute myeloid leukaemia using
      whole exome sequencing of fingernail derived DNA as germline control.
AB  - Recent advances in next-generation sequencing have made it possible to perform
      genome wide identification of somatic mutation in cancers. Most studies focus on
      identifying somatic mutations in the protein coding portion of the genome using
      whole exome sequencing (WES). Every human genome has around 4 million single
      nucleotide polymorphisms (SNPs). A sizeable fraction of these germline SNPs is
      very rare and will not be found in the databases. Thus, in order to unambiguously
      identify somatic mutation, it is absolutely necessary to know the germline SNPs
      of the patient. While a blood sample can serve as source of germline DNA from
      patients with solid tumours, obtaining germline DNA from patients with
      haematological malignancies is very difficult. Tumor cells often infiltrate the
      skin, and their DNA can be found in saliva and buccal swab samples. The DNA in
      the tips of nails stems from keratinocytes that have undergone keratinization
      several months ago. DNA was successfully extracted from nail clippings of 5
      probands for WES. We were able to identify somatic mutations in one tumor exome
      by using the nail exome as germline reference. Our results demonstrate that nail
      DNA is a reliable source of germline DNA in the setting of hematological
      malignancies.

PMID- 30213992
TI  - Non-thermal plasma treated solution with potential as a novel therapeutic agent
      for nasal mucosa regeneration.
AB  - Adequate and rapid mucosal regeneration is one of the most important factors in
      the healing process of nasal mucosa after surgery or trauma. In particular,
      delayed mucosal regeneration after surgery is an important cause of surgical
      failure. However, no effective treatment is available yet. Non-thermal plasma
      (NTP) has several medical effects, but the existing probe type is limited to
      local direct treatment. Therefore, we investigated the various effects using
      liquid type plasma to overcome this limitation. In addition, the therapeutic
      effects of non-thermal plasma treated solution (NTS) on nasal mucosa have yet to
      be determined. Experiments were carried out using BEAS-2B, a human bronchial
      epithelial cell line similar to nasal mucosa epithelium. NTS had no cytotoxicity
      to the BEAS-2B cells and enhanced cell proliferation. NTS also promoted migration
      of BEAS-2B cells. NTS increased cell proliferation and migration via epidermal
      growth factor receptor (EGFR) activities and epithelial-to-mesenchymal transition
      (EMT) signaling. Furthermore, NTS enhanced wound healing of nasal mucosa in an
      animal model. Accordingly, NTS promotes nasal mucosa wound healing by increasing
      cell proliferation and migration. These findings suggest the therapeutic
      potential of NTS in nasal mucosa wound healing.

PMID- 30213993
TI  - Microwave treatment of the cornea leads to localised disruption of the
      extracellular matrix.
AB  - Microwave keratoplasty is a thermo-refractive surgical procedure that can correct
      myopia (short-sightedness) and pathologic corneal steepening by using microwave
      energy to cause localised shrinkage around an annulus of the cornea leading to
      its flattening and vision correction. The effects on the corneal extracellular
      matrix, however, have not yet been evaluated, thus the current study to assess
      post-procedure ultrastructural changes in an in-vivo rabbit model. To achieve
      this a series of small-angle x-ray scattering (SAXS) experiments were carried out
      across whole transects of treated and untreated rabbit corneas at 0.25 mm
      intervals, which indicated no significant change in collagen intra-fibrillar
      parameters (i.e. collagen fibril diameter or axial D-period), whereas inter
      fibrillar measures (i.e. fibril spacing and the degree of spatial order) were
      markedly altered in microwave-treated regions of the cornea. These structural
      matrix alterations in microwave-treated corneas have predicted implications for
      corneal biomechanical strength and tissue transparency, and, we contend,
      potentially render microwave-treated corneas resistant to surgical stabilization
      using corneal cross-linking procedures currently employed to combat refractive
      error caused by corneal steepening.

PMID- 30213994
TI  - Oocyte growth, follicular complex formation and extracellular-matrix remodeling
      in ovarian maturation of the imperial zebra pleco fish Hypancistrus zebra.
AB  - This contribution describes the growth of oocytes, addressing the formation of
      structures that compose the follicular complex, as well as the remodeling of the
      extracellular matrix, specifically laminin, fibronectin and type IV collagen
      during gonadal maturation. Thirty-seven females of the Acari zebra fish,
      Hypancistrus zebra were captured and the ovaries were submitted to histological
      processing for light and electron microscopy and immunohistochemistry techniques.
      Oogonia and four stages (I - IV) of oocytes were distinguished, and structures
      such as the postovulatory follicle and atretic oocytes (initial and advanced
      atresia) were observed. The follicular complex consists of the mature oocyte,
      zona radiata (Zr1, Zr2 and Zr3), follicular cells, basement membrane and theca.
      During oocyte growth, proteins of the extracellular matrix showed different
      intensities of staining. Based on these observations, a model of oocyte growth is
      proposed to define specific characteristics of the oocyte and the remodeling of
      the extracellular matrix in the ovary of H. zebra. This model of oocyte growth
      can be extended to other species of ornamental fishes. This study contributes
      data for induced fertilization and eventual conservation of this species.

PMID- 30213995
TI  - Fabrication and Characterization of Glucose Biosensors by Using Hydrothermally
      Grown ZnO Nanorods.
AB  - Highly oriented ZnO nanorod (NR) arrays were fabricated on a seeded substrate
      through a hydrothermal route. The prepared ZnO nanorods were used as an
      amperometric enzyme electrode, in which glucose oxidase (GOx) was immobilised
      through physical adsorption. The modified electrode was designated as
      Nafion/GOx/ZnO NRs/ITO. The morphology and structural properties of the
      fabricated ZnO nanorods were analysed using field-emission scanning electron
      microscope and X-ray diffractometer. The electrochemical properties of the
      fabricated biosensor were studied by cyclic voltammetry and amperometry.
      Electrolyte pH, electrolyte temperature and enzyme concentration used for
      immobilisation were the examined parameters influencing enzyme activity and
      biosensor performance. The immobilised enzyme electrode showed good GOx retention
      activity. The amount of electroactive GOx was 7.82 * 10-8 mol/cm2, which was
      relatively higher than previously reported values. The Nafion/GOx/ZnO NRs/ITO
      electrode also displayed a linear response to glucose ranging from 0.05 mM to 1
      mM, with a sensitivity of 48.75 uA/mM and a low Michaelis-Menten constant of 0.34
      mM. Thus, the modified electrode can be used as a highly sensitive third
      generation glucose biosensor with high resistance against interfering species,
      such as ascorbic acid, uric acid and L-cysteine. The applicability of the
      modified electrode was tested using human blood samples. Results were comparable
      with those obtained using a standard glucometer, indicating the excellent
      performance of the modified electrode.

PMID- 30213996
TI  - Pollination niche availability facilitates colonization of Guettarda speciosa
      with heteromorphic self-incompatibility on oceanic islands.
AB  - Obligate out-breeding plants are considered relatively disadvantageous comparing
      with self-breeding plants when colonizing oceanic islets following long-distance
      dispersal owing to mate and pollinator limitation. The rarity of heterostyly, a
      typical out-breeding system, on oceanic islands seems a good proof. However, a
      heterostylous plant, Guettarda speciosa, is widely distributed on most tropical
      oceanic islets. Our research demonstrates that its heteromorphic self
      incompatibility, plus herkogamy and long flower tube make it rely on pollinator
      for sexual reproduction, which is generally considered "disadvantageous" for
      island colonization. We hypothesize that available pollination niche will be a
      key factor for its colonization on islands. Our studies on remote coral islands
      show that G. speciosa has built equilibrium population with a 1:1 morph ratio. It
      could obtain pollination niche from the hawkmoth Agrius convolvuli. A pioneer
      island plant Ipomoea pes-caprae sustain the pollination niche by providing
      trophic resource for the larvae of the pollinator. Geographic pattern drawn by
      Ecological Niche Modelling further indicates the interaction between G. speciosa,
      A. convolvuli and I. pes-caprae can be bounded on those remote oceanic islands,
      explaining the colonization of G. speciosa distylous population. These findings
      demonstrated obligate out-breeding system could be maintained to acclimatize long
      distance dispersal, if the pollination niche is available.

PMID- 30213997
TI  - Earth's Subdecadal Angular Momentum Balance from Deformation and Rotation Data.
AB  - Length-of-Day (LOD) measurements represent variations in the angular momentum of
      the solid Earth (crust and mantle). There is a known ~6-year LOD signal suspected
      to be due to core-mantle coupling. If it is, then the core flow associated with
      the 6-year LOD signal may also deform the mantle, causing a 6-year signal in the
      deformation of the Earth's surface. Stacking of Global Positioning System (GPS)
      data is found to contain a ~6-year radial deformation signal. We inverted the
      deformation signal for the outer core's flow and equivalent angular momentum
      changes, finding good agreement with the LOD signal in some cases. These results
      support the idea of subdecadal core-mantle coupling, but are not robust.
      Interpretation of the results must also take into account methodological
      limitations. Gravitational field changes resulting from solid Earth deformation
      were also computed and found to be smaller than the errors in the currently
      available data.

PMID- 30213998
TI  - Somatosensory Response to Trigeminal Stimulation: A Functional Near-Infrared
      Spectroscopy (fNIRS) Study.
AB  - Functional near-infrared spectroscopy (fNIRS) is an optical imaging technique
      measuring relative hemodynamic changes in superficial cortical structures. It has
      successfully been applied to detect a hemodynamic response in the somatosensory
      cortex evoked by irritating mechanical, electrical, and heat stimulations of
      limbs or the face. The aim of the current study was to explore the feasibility of
      fNIRS to detect respective responses evoked by irritating chemical stimulations
      of the nasal divisions of the trigeminal nerve. In two experiments, healthy
      subjects were exposed to acetic acid and ethyl acetate presented using a
      respiration-synchronized olfactometer. Results demonstrated that fNIRS can detect
      a signal in both hemispheres after birhinal (experiment 1: n = 14) and monorhinal
      (experiment 2: n = 12) stimulations using acetic acid but not ethyl acetate. This
      is a first evidence that fNIRS might be a suitable imaging technique to assess
      chemosensory neuronal correlates in the somatosensory cortex thereby offering a
      new, portable method to evaluate the irritating properties of certain volatiles
      in an objective, nonverbal, easy, and comparably inexpensive manner.

PMID- 30213999
TI  - Tracking Fish Abundance by Underwater Image Recognition.
AB  - Marine cabled video-observatories allow the non-destructive sampling of species
      at frequencies and durations that have never been attained before. Nevertheless,
      the lack of appropriate methods to automatically process video imagery limits
      this technology for the purposes of ecosystem monitoring. Automation is a
      prerequisite to deal with the huge quantities of video footage captured by
      cameras, which can then transform these devices into true autonomous sensors. In
      this study, we have developed a novel methodology that is based on genetic
      programming for content-based image analysis. Our aim was to capture the temporal
      dynamics of fish abundance. We processed more than 20,000 images that were
      acquired in a challenging real-world coastal scenario at the OBSEA-EMSO testing
      site. The images were collected at 30-min. frequency, continuously for two years,
      over day and night. The highly variable environmental conditions allowed us to
      test the effectiveness of our approach under changing light radiation, water
      turbidity, background confusion, and bio-fouling growth on the camera housing.
      The automated recognition results were highly correlated with the manual counts
      and they were highly reliable when used to track fish variations at different
      hourly, daily, and monthly time scales. In addition, our methodology could be
      easily transferred to other cabled video-observatories.

PMID- 30214000
TI  - Infant-directed speech facilitates seven-month-old infants' cortical tracking of
      speech.
AB  - This study assessed cortical tracking of temporal information in incoming natural
      speech in seven-month-old infants. Cortical tracking refers to the process by
      which neural activity follows the dynamic patterns of the speech input. In
      adults, it has been shown to involve attentional mechanisms and to facilitate
      effective speech encoding. However, in infants, cortical tracking or its effects
      on speech processing have not been investigated. This study measured cortical
      tracking of speech in infants and, given the involvement of attentional
      mechanisms in this process, cortical tracking of both infant-directed speech
      (IDS), which is highly attractive to infants, and the less captivating adult
      directed speech (ADS), were compared. IDS is the speech register parents use when
      addressing young infants. In comparison to ADS, it is characterised by several
      acoustic qualities that capture infants' attention to linguistic input and assist
      language learning. Seven-month-old infants' cortical responses were recorded via
      electroencephalography as they listened to IDS or ADS recordings. Results showed
      stronger low-frequency cortical tracking of the speech envelope in IDS than in
      ADS. This suggests that IDS has a privileged status in facilitating successful
      cortical tracking of incoming speech which may, in turn, augment infants' early
      speech processing and even later language development.

PMID- 30214001
TI  - Coulomb-bound four- and five-particle intervalley states in an atomically-thin
      semiconductor.
AB  - As hosts for tightly-bound electron-hole pairs carrying quantized angular
      momentum, atomically-thin semiconductors of transition metal dichalcogenides
      (TMDCs) provide an appealing platform for optically addressing the valley degree
      of freedom. In particular, the valleytronic properties of neutral and charged
      excitons in these systems have been widely investigated. Meanwhile, correlated
      quantum states involving more particles are still elusive and controversial
      despite recent efforts. Here, we present experimental evidence for four-particle
      biexcitons and five-particle exciton-trions in high-quality monolayer tungsten
      diselenide. Through charge doping, thermal activation, and magnetic-field tuning
      measurements, we determine that the biexciton and the exciton-trion are bound
      with respect to the bright exciton and the trion, respectively. Further, both the
      biexciton and the exciton-trion are intervalley complexes involving dark
      excitons, giving rise to emissions with large, negative valley polarization in
      contrast to that of the two-particle excitons. Our studies provide opportunities
      for building valleytronic quantum devices harnessing high-order TMDC excitations.

PMID- 30214002
TI  - A new method for discovering EMAST sequences in animal models of cancer.
AB  - Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST)
      occur in up to 60% of colorectal cancers and may associate with aggressive and
      advanced disease in patients. Although EMAST occurs in many cancer types, current
      understanding is limited due to the lack of an animal model. Reported here is the
      design and implementation of an algorithm for detecting EMAST repeats in mice.
      This algorithm incorporates properties of known human EMAST sequences to identify
      repeat sequences in animal genomes and was able to identify EMAST-like sequences
      in the mouse. Seven of the identified repeats were analyzed further in a colon
      cancer mouse model and six of the seven displayed EMAST instability
      characteristic of that seen in human colorectal cancers. In conclusion, the
      algorithm developed successfully identified EMAST repeats in an animal genome
      and, for the first time, EMAST has been shown to occur in a mouse model of colon
      cancer.

PMID- 30214003
TI  - Nitrogen cycle microorganisms can be reactivated after Space exposure.
AB  - Long-term human Space missions depend on regenerative life support systems (RLSS)
      to produce food, water and oxygen from waste and metabolic products. Microbial
      biotechnology is efficient for nitrogen conversion, with nitrate or nitrogen gas
      as desirable products. A prerequisite to bioreactor operation in Space is the
      feasibility to reactivate cells exposed to microgravity and radiation. In this
      study, microorganisms capable of essential nitrogen cycle conversions were sent
      on a 44-days FOTON-M4 flight to Low Earth Orbit (LEO) and exposed to 10-3-10-4 g
      (gravitational constant) and 687 +/- 170 uGy (Gray) d-1 (20 +/- 4  degrees C),
      about the double of the radiation prevailing in the International Space Station
      (ISS). After return to Earth, axenic cultures, defined and reactor communities of
      ureolytic bacteria, ammonia oxidizing archaea and bacteria, nitrite oxidizing
      bacteria, denitrifiers and anammox bacteria could all be reactivated. Space
      exposure generally yielded similar or even higher nitrogen conversion rates as
      terrestrial preservation at a similar temperature, while terrestrial storage at 4
      degrees C mostly resulted in the highest rates. Refrigerated Space exposure is
      proposed as a strategy to maximize the reactivation potential. For the first
      time, the combined potential of ureolysis, nitritation, nitratation,
      denitrification (nitrate reducing activity) and anammox is demonstrated as key
      enabler for resource recovery in human Space exploration.

PMID- 30214004
TI  - Defining animal welfare standards in hunting: body mass determines thresholds for
      incapacitation time and flight distance.
AB  - Shooting is an important tool for managing terrestrial wildlife populations
      worldwide. To date, however, there has been few quantitative methods available
      enabling assessment of the animal welfare outcomes of rifle hunting. We apply a
      variety of factors to model flight distance (distance travelled by an animal
      after bullet impact) and incapacitation from the moment of bullet impact. These
      factors include body mass, allometric and isometric scaling, comparative
      physiology, wound ballistics and linear kinematics. This approach provides for
      the first time a method for quantifying and grading the quality of shooting
      processes by examining only body mass and flight distance. Our model is a
      universally applicable tool for measuring animal welfare outcomes of shooting
      regimes both within and among species. For management agencies the model should
      be a practical tool for monitoring and evaluating animal welfare outcomes
      regarding shooting of mammalian populations.

PMID- 30214005
TI  - Soil resources and element stocks in drylands to face global issues.
AB  - Drylands (hyperarid, arid, semiarid, and dry subhumid ecosystems) cover almost
      half of Earth's land surface and are highly vulnerable to environmental
      pressures. Here we provide an inventory of soil properties including carbon (C),
      nitrogen (N), and phosphorus (P) stocks within the current boundaries of
      drylands, aimed at serving as a benchmark in the face of future challenges
      including increased population, food security, desertification, and climate
      change. Aridity limits plant production and results in poorly developed soils,
      with coarse texture, low C:N and C:P, scarce organic matter, and high
      vulnerability to erosion. Dryland soils store 646 Pg of organic C to 2 m, the
      equivalent of 32% of the global soil organic C pool. The magnitude of the
      historic loss of C from dryland soils due to human land use and cover change and
      their typically low C:N and C:P suggest high potential to build up soil organic
      matter, but coarse soil textures may limit protection and stabilization
      processes. Restoring, preserving, and increasing soil organic matter in drylands
      may help slow down rising levels of atmospheric carbon dioxide by sequestering C,
      and is strongly needed to enhance food security and reduce the risk of land
      degradation and desertification.

PMID- 30214006
TI  - Epalrestat, an Aldose Reductase Inhibitor, Restores Erectile Function in
      Streptozocin-induced Diabetic Rats.
AB  - Epalrestat, an aldose reductase inhibitor (ARI), was adopted to improve the
      function of peripheral nerves in diabetic patients. The aim of this study was to
      investigate whether epalrestat could restore the erectile function of diabetic
      erectile dysfunction using a rat model. From June 2016, 24 rats were given
      streptozocin (STZ) to induce the diabetic rat model, and epalrestat was
      administered to ten diabetic erectile dysfunction (DED) rats. Intracavernous
      pressure (ICP) and mean systemic arterial pressure (MAP), levels of aldose
      reductase (AR), nerve growth factor (NGF), neuronal nitric oxide synthase (nNOS),
      alpha-smooth muscle antigen (alpha-SMA), and von Willebrand factor (vWF) in the
      corpus cavernosum were analyzed. We discovered that epalrestat acted on cavernous
      tissue and partly restored erectile function. NGF and nNOS levels in the corpora
      were increased after treatment with epalrestat. We also found that the content of
      alpha-SMA-positive smooth muscle cells and vWF-positive endothelial cells in the
      corpora cavernosum were declined. Accordingly, epalrestat might improve erectile
      function by increasing the upregulation of NGF and nNOS to restore the function
      of the dorsal nerve of the penis.

PMID- 30214007
TI  - Blocking HIF signaling via novel inhibitors of CA9 and APE1/Ref-1 dramatically
      affects pancreatic cancer cell survival.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has reactive stroma that promotes tumor
      signaling, fibrosis, inflammation, and hypoxia, which activates HIF-1alpha to
      increase tumor cell metastasis and therapeutic resistance. Carbonic anhydrase IX
      (CA9) stabilizes intracellular pH following induction by HIF-1alpha. Redox
      effector factor-1 (APE1/Ref-1) is a multifunctional protein with redox signaling
      activity that converts certain oxidized transcription factors to a reduced state,
      enabling them to upregulate tumor-promoting genes. Our studies evaluate PDAC
      hypoxia responses and APE1/Ref-1 redox signaling contributions to HIF-1alpha
      mediated CA9 transcription. Our previous studies implicated this pathway in PDAC
      cell survival under hypoxia. We expand those studies, comparing drug responses
      using patient-derived PDAC cells displaying differential hypoxic responses in 3D
      spheroid tumor-stroma models to characterize second generation APE1/Ref-1 redox
      signaling and CA9 inhibitors. Our data demonstrates that HIF-1alpha-mediated CA9
      induction differs between patient-derived PDAC cells and that APE1/Ref-1 redox
      inhibition attenuates this induction by decreasing hypoxia-induced HIF-1 DNA
      binding. Dual-targeting of APE1/Ref-1 and CA9 in 3D spheroids demonstrated that
      this combination effectively kills PDAC tumor cells displaying drastically
      different levels of CA9. New APE1/Ref-1 and CA9 inhibitors were significantly
      more potent alone and in combination, highlighting the potential of combination
      therapy targeting the APE1-Ref-1 signaling axis with significant clinical
      potential.

PMID- 30214008
TI  - Whole genome sequencing identifies high-impact variants in well-known
      pharmacogenomic genes.
AB  - More than 1100 genetic loci have been correlated with drug response outcomes but
      disproportionately few have been translated into clinical practice. One
      explanation for the low rate of clinical implementation is that the majority of
      associated variants may be in linkage disequilibrium (LD) with the causal
      variants, which are often elusive. This study aims to identify and characterize
      likely causal variants within well-established pharmacogenomic genes using next
      generation sequencing data from the 1000 Genomes Project. We identified 69,319
      genetic variations within 160 pharmacogenomic genes, of which 8207 variants are
      in strong LD (r2>0.8) with known pharmacogenomic variants. Of the latter, eight
      are coding or structural variants predicted to have high impact, with 19
      additional missense variants that are predicted to have moderate impact. In
      conclusion, we identified putatively functional variants within known
      pharmacogenomics loci that could account for the association signals and
      represent the missing causative variants underlying drug response phenotypes.

PMID- 30214010
TI  - Longstanding alopecia and nail dystrophy are associated with more severe overall
      chronic graft-versus-host disease in adults.

PMID- 30214009
TI  - Metabolic gene expression and epigenetic effects of the ketone body beta
      hydroxybutyrate on H3K9ac in bovine cells, oocytes and embryos.
AB  - The rapid decline in fertility that has been occurring to high-producing dairy
      cows in the past 50 years seems to be associated with metabolic disturbances such
      as ketosis, supporting the need for research to improve our understanding of the
      relations among the diet, metabolism and embryonic development. Recently, the
      ketone body beta-hydroxybutyrate (BOHB) was demonstrated to be a potent inhibitor
      of histone deacetylases (HDACs). Herein, we performed a series of experiments
      aiming to investigate the epigenetic effects of BOHB on histone acetylation in
      somatic cells, cumulus-oocyte complexes (COCs) and somatic cell nuclear transfer
      (SCNT) embryos. Treatment with BOHB does not increase histone acetylation in
      cells but stimulates genes associated with ketolysis and master regulators of
      metabolism. We further demonstrated that maturing COCs with high levels of BOHB
      does not affect their maturation rate or histone acetylation but increases the
      expression of PPARA in cumulus cells. Treatment of somatic cell nuclear transfer
      zygotes with BOHB causes hyperacetylation, which is maintained until the
      blastocyst stage, causing enhanced FOXO3A expression and blastocyst production.
      Our data shed light on the epigenetic mechanisms caused by BOHB in bovine cells
      and embryos and provide a better understanding of the connection between
      nutrition and reproduction.

PMID- 30214013
TI  - The Quality of Life Measurement in Recurrent Acute Pancreatitis Needs to be More
      Accurate.

PMID- 30214012
TI  - Combining BH3-mimetics to target both BCL-2 and MCL1 has potent activity in pre
      clinical models of acute myeloid leukemia.
AB  - Improving outcomes in acute myeloid leukemia (AML) remains a major clinical
      challenge. Overexpression of pro-survival BCL-2 family members rendering
      transformed cells resistant to cytotoxic drugs is a common theme in cancer.
      Targeting BCL-2 with the BH3-mimetic venetoclax is active in AML when combined
      with low-dose chemotherapy or hypomethylating agents. We now report the pre
      clinical anti-leukemic efficacy of a novel BCL-2 inhibitor S55746, which
      demonstrates synergistic pro-apoptotic activity in combination with the MCL1
      inhibitor S63845. Activity of the combination was caspase and BAX/BAK dependent,
      superior to combination with standard cytotoxic AML drugs and active against a
      broad spectrum of poor risk genotypes, including primary samples from patients
      with chemoresistant AML. Co-targeting BCL-2 and MCL1 was more effective against
      leukemic, compared to normal hematopoietic progenitors, suggesting a therapeutic
      window of activity. Finally, S55746 combined with S63845 prolonged survival in
      xenograft models of AML and suppressed patient-derived leukemia but not normal
      hematopoietic cells in bone marrow of engrafted mice. In conclusion, a dual BH3
      mimetic approach is feasible, highly synergistic, and active in diverse models of
      human AML. This approach has strong clinical potential to rapidly suppress
      leukemia, with reduced toxicity to normal hematopoietic precursors compared to
      chemotherapy.

PMID- 30214011
TI  - NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel
      disease.
AB  - Anti-microbial signaling pathways are normally triggered by innate immune
      receptors when detecting pathogenic microbes to provide protective immunity. Here
      we show that the inflammasome sensor Nlrp1 aggravates DSS-induced experimental
      mouse colitis by limiting beneficial, butyrate-producing Clostridiales in the
      gut. The colitis-protective effects of Nlrp1 deficiency are thus reversed by
      vancomycin treatment, but recapitulated with butyrate supplementation in wild
      type mice. Moreover, an activating mutation in Nlrp1a increases IL-18 and
      IFNgamma production, and decreases colonic butyrate to exacerbate colitis. We
      also show that, in patients with ulcerative colitis, increased NLRP1 in inflamed
      regions of the colon is associated with increased IFN-gamma. In this context,
      NLRP1, IL-18 or IFN-gamma expression negatively correlates with the abundance of
      Clostridiales in human rectal mucosal biopsies. Our data identify the NLRP1
      inflammasome to be a key negative regulator of protective, butyrate-producing
      commensals, which therefore promotes inflammatory bowel disease.

PMID- 30214014
TI  - Reply to Johnson et al. Regarding Optimizing Selection of Biologics in
      Inflammatory Bowel Disease: Development of an Online Patient Decision Aid Using
      Conjoint Analysis.

PMID- 30214015
TI  - Palmoplantar Hyperkeratosis and Strong Family History of Esophageal Cancer:
      Tylosis or Not?

PMID- 30214016
TI  - Predictive accuracy of partial coherence interferometry and swept-source optical
      coherence tomography for intraocular lens power calculation.
AB  - The purpose of this study is to compare the predictive accuracy of intraocular
      lens (IOL) calculations made with partial coherence interferometry (PCI,
      IOLMaster, version 5) and swept-source optical coherence tomography (SS-OCT,
      Argos). Axial length (AL), mean keratometry value (K), and anterior chamber depth
      (ACD) were obtained using PCI and SS-OCT optical biometers. Intraocular lens
      (IOL) power calculations were made using the Barret-Universal II, Haigis, Hoffer
      Q, SRK/T, and T2 formulas and compared the predictive accuracy between biometers.
      In 153 eyes (153 patients), axial length measurements made with PCI (24.65 +/-
      2.35 mm) and SS-OCT (24.62 +/- 2.29 mm) were significantly different (P < 0.001).
      Corneal power (P = 0.97) and anterior chamber depth (P = 0.51) were not
      significantly different between biometer. The mean absolute error was not
      significantly different between the five IOL power calculation formulas for
      either PCI or SS-OCT measurements. When AL was 24.5-26.0 mm, mean absolute error
      derived from SS-OCT was smaller than mean absolute error derived from PCI for all
      five IOL power calculation formulas (all P < 0.05). In conclusion, predictive
      accuracy of PCI and SS-OCT were nearly the same. However, in medium-long eyes,
      the predictive accuracy of SS-OCT for IOL calculations was higher.

PMID- 30214017
TI  - Noninvasive assessment of characteristics of novel anti-HER2 antibodies by
      molecular imaging in a human gastric cancer xenograft-bearing mouse model.
AB  - Human epidermal growth factor receptor 2 (HER2) overexpression occurs in various
      types of cancers. Regarding the anti-HER2 targeted therapies showed superior
      treatment outcomes in several (pre)clinical studies, we used multimodality image
      to rapidly select novel HER2-targeting antibodies for further therapeutics
      development. The four anti-HER2 antibodies (H32 IgG, 75 IgG, 61 IgG, and
      trastuzumab) labeled with either In-111 or a DyLight680 fluorescent dye were
      applied to perform cellular uptake, endocytosis, optical/microSPECT/CT imaging
      and biodistribution studies. In vitro and in vivo relative effectiveness of these
      antibodies were also compared in an N87 gastric cancer xenograft model. The
      internalized radioactivity of [111In]61 IgG in N87 cells increased from 33% at 12
      hr to 56% at 48 hr after incubation, while the majority of other antibodies
      stayed on the cell membranes. Among these antibodies, 61 IgG showed the highest
      accumulation in tumors with the tumor-to-muscle ratio (T/M) of 131 +/- 61.4 and
      19.13 +/- 3.42 conducted by IVIS and microSPECT/CT, respectively. We demonstrated
      that multimodality imaging is a reliable approach for selecting potential
      antibodies and found that 61 IgG manifested significant tumor accumulation with
      elevated internalization rate thus could be a suitable candidate for further
      development of new HER2-targeted therapies.

PMID- 30214019
TI  - Tafamidis: a new treatment for ATTR cardiomyopathy.

PMID- 30214020
TI  - No benefit of n-3 fatty acid supplements in diabetes.

PMID- 30214018
TI  - Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state
      decisions.
AB  - Groucho related gene 5 (GRG5) is a multifunctional protein that has been
      implicated in late embryonic and postnatal mouse development. Here, we describe a
      previously unknown role of GRG5 in early developmental stages by analyzing its
      function in stem cell fate decisions. By both loss and gain of function
      approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem
      Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self
      renewal and acquisition of cancer cell-like properties. The malignant
      characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its
      pro-oncogenic potential. Furthermore, transcriptomic analysis and cell
      differentiation approaches underline GRG5 as a multifaceted signaling regulator
      that represses mesendodermal-related genes. When ESCs exit pluripotency, GRG5
      promotes neuroectodermal specification via Wnt and BMP signaling suppression.
      Moreover, GRG5 promotes the neuronal reprogramming of fibroblasts and maintains
      the self-renewal of Neural Stem Cells (NSCs) by sustaining the activity of
      Notch/Hes and Stat3 signaling pathways. In summary, our results demonstrate that
      GRG5 has pleiotropic roles in stem cell biology functioning as a stemness factor
      and a neural fate specifier.

PMID- 30214022
TI  - HIV-1's fingerprint.

PMID- 30214021
TI  - Cardiovascular safety of lorcaserin.

PMID- 30214023
TI  - Neonatal encephalopathy versus Hypoxic-Ischemic Encephalopathy.

PMID- 30214024
TI  - Fucosylated oligosaccharides in mother's milk alleviate the effects of caesarean
      birth on infant gut microbiota.
AB  - One of the most abundant components in human milk is formed by oligosaccharides,
      which are poorly digested by the infant. The oligosaccharide composition of
      breast milk varies between mothers, and is dependent on maternal secretor (FUT2)
      genotype. Secretor mothers produce milk containing alpha1-2 fucosylated human
      milk oligosaccharides, which are absent in the milk of non-secretor mothers.
      Several strains of bacteria in the infant gut have the capacity to utilise human
      milk oligosaccharides (HMOs). Here we investigate the differences in infant gut
      microbiota composition between secretor (N = 76) and non-secretor (N = 15)
      mothers, taking into account birth mode. In the vaginally born infants, maternal
      secretor status was not associated with microbiota composition. In the caesarean
      born, however, many of the caesarean-associated microbiota patterns were more
      pronounced among the infants of non-secretor mothers compared to those of
      secretor mothers. Particularly bifidobacteria were strongly depleted and
      enterococci increased among the caesarean-born infants of non-secretor mothers.
      Furthermore, Akkermansia was increased in the section-born infants of secretor
      mothers, supporting the suggestion that this organism may degrade HMOs. The
      results indicate that maternal secretor status may be particularly influential in
      infants with compromised microbiota development, and that these infants could
      benefit from corrective supplementation.

PMID- 30214025
TI  - Peanut-Shell Biochar and Biogas Slurry Improve Soil Properties in the North China
      Plain: A Four-Year Field Study.
AB  - Biochar and biogas slurry have been proved to improve the quality of some soil
      types, but the long-term effects on fluvo-aquic soil are not fully understood.
      This study aimed to compare the continuity effects of peanut-shell biochar and
      biogas slurry on the physicochemical properties, microbial population size, and
      enzyme activities of fluvo-aquic soil. We conducted a four-year field experiment
      of winter wheat-summer maize rotation in the North China Plain. Along with equal
      nitrogen inputs, three treatments were applied-conventional fertilizers, peanut
      shell biochar, and hoggery biogas slurry-after which various soil quality
      indicators were compared. Compared with those of control, both biochar and biogas
      slurry increased the soil total nitrogen and organic matter content, and improved
      soil aggregation, microbial biomass, and actinomycetes. Biogas slurry decreased
      soil pH and improved urease and protease activities. With biochar and biogas
      slurry treatments, wheat yield increased by 8.46% and 23.47%, and maize yield by
      18% and 15.46%, respectively. Biogas slurry increased the content of crude
      protein and starch in the grains. Both biogas slurry and peanut-shell biochar
      improved fluvo-aquic soil nutrient content, water-stable macroaggregates, and
      microbial population, which might be related to their high nutrient content,
      large specific surface area, adsorption capacity, and functional groups. Biogas
      slurry generally exhibited stronger effects than biochar probably because of its
      richness in nutrients and bioactive substances.

PMID- 30214026
TI  - Efficient generation of neutral and charged biexcitons in encapsulated WSe2
      monolayers.
AB  - Higher-order correlated excitonic states arise from the mutual interactions of
      excitons, which generally requires a significant exciton density and therefore
      high excitation levels. Here, we report the emergence of two biexcitons species,
      one neutral and one charged, in monolayer tungsten diselenide under moderate
      continuous-wave excitation. The efficient formation of biexcitons is facilitated
      by the long lifetime of the dark exciton state associated with a spin-forbidden
      transition, as well as improved sample quality from encapsulation between
      hexagonal boron nitride layers. From studies of the polarization and magnetic
      field dependence of the neutral biexciton, we conclude that this species is
      composed of a bright and a dark excitons residing in opposite valleys in momentum
      space. Our observations demonstrate that the distinctive features associated with
      biexciton states can be accessed at low light intensities and excitation
      densities.

PMID- 30214027
TI  - Attention allows the SNARC effect to operate on multiple number lines.
AB  - To investigate whether participants can activate only one spatially oriented
      number line at a time or multiple number lines simultaneously, they were asked to
      solve a unit magnitude comparison task (unit smaller/larger than 5) and a parity
      judgment task (even/odd) on two-digit numbers. In both these primary tasks,
      decades were irrelevant. After some of the primary task trials (randomly),
      participants were asked to additionally solve a secondary task based on the
      previously presented number. In Experiment 1, they had to decide whether the two
      digit number presented for the primary task was larger or smaller than 50. Thus,
      for the secondary task decades were relevant. In contrast, in Experiment 2, the
      secondary task was a color judgment task, which means decades were irrelevant. In
      Experiment 1, decades' and units' magnitudes influenced the spatial association
      of numbers separately. In contrast, in Experiment 2, only the units were
      spatially associated with magnitude. It was concluded that multiple number lines
      (one for units and one for decades) can be activated if attention is focused on
      multiple, separate magnitude attributes.

PMID- 30214028
TI  - Soil exchange rates of COS and CO18O differ with the diversity of microbial
      communities and their carbonic anhydrase enzymes.
AB  - Differentiating the contributions of photosynthesis and respiration to the global
      carbon cycle is critical for improving predictive climate models. Carbonic
      anhydrase (CA) activity in leaves is responsible for the largest biosphere
      atmosphere trace gas fluxes of carbonyl sulfide (COS) and the oxygen-18
      isotopologue of carbon dioxide (CO18O) that both reflect gross photosynthetic
      rates. However, CA activity also occurs in soils and will be a source of
      uncertainty in the use of COS and CO18O as carbon cycle tracers until process
      based constraints are improved. In this study, we measured COS and CO18O exchange
      rates and estimated the corresponding CA activity in soils from a range of biomes
      and land use types. Soil CA activity was not uniform for COS and CO2, and
      patterns of divergence were related to microbial community composition and CA
      gene expression patterns. In some cases, the same microbial taxa and CA classes
      catalyzed both COS and CO2 reactions in soil, but in other cases the specificity
      towards the two substrates differed markedly. CA activity for COS was related to
      fungal taxa and beta-D-CA expression, whereas CA activity for CO2 was related to
      algal and bacterial taxa and alpha-CA expression. This study integrates gas
      exchange measurements, enzyme activity models, and characterization of soil
      taxonomic and genetic diversity to build connections between CA activity and the
      soil microbiome. Importantly, our results identify kinetic parameters to
      represent soil CA activity during application of COS and CO18O as carbon cycle
      tracers.

PMID- 30214030
TI  - Novel biomarker profiles in experimental aged maternal mice with hypertensive
      disorders of pregnancy.
AB  - Recently, advanced maternal age (AMA) has increased in Western countries because
      of late marriage and advances in assisted reproductive technology. One major
      complication of AMA is hypertensive disorders of pregnancy (HDP). While clinical
      investigations into human AMA have been reported, there has been limited
      information obtained from basic research. In this investigation, we established
      the AMA mouse model using aged pregnant ICR mice. We demonstrated that the
      phenotypes of aged pregnant ICR mice reflect the same characteristics as human
      AMA. The significant findings of our investigation are as follows: (1) The AMA
      mouse model manifested the same complication phenotypes of human AMA, including
      maternal obesity, declining fertility, small for gestational age, and a higher
      rate of intrauterine fetal death; (2) The AMA mouse model exhibited an increasing
      systolic blood pressure at late gestation (108.2 +/- 7.7 vs. 92.7 +/- 5.7 mmHg, P
      < 0.01) that normalized after delivery similar to human HDP patients; and (3)
      While HDP and placental dysfunction are complicated, AMA mice and human HDP AMA
      patients manifested a low serum soluble fms-like tyrosine kinase-1 (sFlt-1) level
      in late gestation (AMA group vs. control group, mice, 16800.0 +/- 10709.5 vs.
      26611.9 +/- 8702.0 pg/mL, respectively, P < 0.01; human, 8507.6 +/- 3298.7 vs.
      14816.9 +/- 5413.5 pg/mL, respectively, P < 0.05). In conclusion, the aged
      pregnant mouse model resembled human AMA. The AMA mouse model was complicated
      with HDP despite the low serum sFlt-1 level. Our findings provide evidence that
      the serum sFlt-1 level does not necessarily reflect the conventional pathogenesis
      of HDP in aged human and murine pregnancies and may contribute to the future
      management of HDP in AMA.

PMID- 30214029
TI  - Low birthweight in second children after nurse home visiting.
AB  - OBJECTIVE: To examine low birthweight and preterm birth of second children born
      to home-visited first-time mothers. SUBJECTS: Women were previously recruited for
      a randomized controlled trial of the home visiting model disseminated as Nurse
      Family Partnership. 512 of these women had second children within 18 years of the
      first child's birth, and were included in our sample. RESULTS: The intervention
      was associated with a lower likelihood of low birthweight for second children
      (odds ratio: 0.51, 95% CI: 0.27, 0.97), an effect apparent only if the first-born
      had low birthweight and mediated by close birth spacing. These moderation and
      mediation patterns were similar in the preterm birth outcome. CONCLUSION: A home
      visiting program provided for first-born children reduced low birthweight for
      second-born children, if the first-born had low birthweight. This finding implies
      a broader impact than previously documented, because few studies have included
      these second children.

PMID- 30214031
TI  - Application of laser scanning cytometry in vascular smooth muscle remodeling.
AB  - Pulmonary artery hyperplasia is the result of proliferation of the pulmonary
      arterial smooth muscles (PASM). Hypoxia-induced PASM proliferation in the fetus
      and the newborn is the primary cause of persistent pulmonary hypertension of the
      newborn (PPHN). This study was performed to characterize the utility of the Laser
      Scanning Cytometry (LSC) method in elucidating arterial cytoskeletal remodeling
      in an in vitro model of PPHN. The aim was to demonstrate the following: (a) LSC
      is a valid method for the analysis of nuclear and cytosolic fluorescence and (b)
      the cumulative effects of mechanical stretch together with hypoxia promote
      reactive oxygen species (ROS) formation. The molecular events in response to
      hypoxia and the mechanical overload of the pulmonary circuit were demonstrated in
      vitro by subjecting hypoxic cultured primary PASM or human airway smooth muscles
      (hASM) to repetitive stretch-relaxation cycles at rates comparable to dynamic
      stretch in vivo. The altered cytoskeleton in the form of filamentous to globular
      actin (F:G actin) ratio was imaged and quantified at the cellular level by LSC as
      an endpoint. LSC can remove the nuclear G-actin fluorescence from the total G
      actin fluorescence. Pulsatile stretch was found to significantly increase the
      total endogenous ROS and superoxide anion release in normoxic and hypoxic
      conditions in primary PASM fibers. The effect of stretch was predominant in
      increasing superoxide anion release, only under hypoxic conditions. These
      findings, obtained by LSC in vitro are amenable to validation in any in vivo
      model of interest. The in vitro model is clinically relevant to human pulmonary
      vascular remodeling.

PMID- 30214032
TI  - Forgotten heroes of the Enigma story.

PMID- 30214033
TI  - Airway obstruction, serum vitamin D and mortality in a 33-year follow-up study.
AB  - BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease and low vitamin D
      status predict mortality, but their combined effect on mortality remains
      inconclusive. We aimed to investigate a joint effect of airway obstruction and
      vitamin D status on mortality in a nationally representative cohort. METHODS: We
      analysed data of 6676 Finnish adults participating between 1978 and 1980 in a
      national health examination survey, undergoing spirometry and having all
      necessary data collected. We followed them up in national registers through
      record linkage until 31 December 2011. We categorised the subjects with
      obstruction using the lower limit of normal (LLN) and the measured serum 25
      hydroxyvitamin-D (s-25(OH)D) into tertiles. RESULTS: Both obstruction and low s
      25(OH)D independently predicted mortality in a multivariate model adjusted also
      for age, sex, smoking, education, leisure physical activity, body mass index,
      asthma and serum C-reactive protein. However, a statistically significant (p =
      0.007) interaction emerged: the adjusted mortality HRs (95% CI's) for s-25(OH)D
      in tertiles among the subjects without and with obstruction were 1.00 (lowest),
      0.96 (0.87-1.05) and 0.89 (0.81-0.98); and 1.00, 0.96 (0.71-1.31) and 0.57 (0.40
      0.80), respectively. CONCLUSIONS: In conclusion, obstruction and low s-25(OH)D
      predict mortality independently of each other. Our findings suggest that low
      vitamin D status might be particularly detrimental among subjects with
      obstruction.

PMID- 30214034
TI  - Serum cholesterol and prostate cancer risk in the Finnish randomized study of
      screening for prostate cancer.
AB  - BACKGROUND: Hypercholesterolemia has been associated with advanced stage prostate
      cancer (PCa), but the role of lipid parameters such as HDL and triglycerides is
      unclear. We examined PCa risk by lipid parameters in a population nested within
      the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). METHODS:
      Cholesterol measurements were available on 17,696 men. During the 17-year median
      follow-up, 2404 PCa cases were diagnosed. Cox regression model was used to
      estimate hazard ratios (HR) and their 95% confidence intervals (95% CI) for
      overall PCa risk and stratified by Gleason grade and tumor stage. We compared
      normolipidemic and hyperlipidemic men on four cholesterol parameters total
      cholesterol (TC), HDL, LDL, and triglycerides (TG), analyzed as time-dependent
      variables. RESULTS: TC in the highest tertile (above 5.1 mmol/l) and LDL above 3
      mmol/l were associated with increased risk of Gleason 8-10 cancer (HR 1.42, 95%
      CI 1.04-1.95 and HR 1.38, 95% CI 1.02-1.86, respectively). Further, overall PCa
      risk was elevated in the 3-year lag time analysis by TC in the highest two
      tertiles (HR 1.27, 95% CI 1.05-1.54 for TC above 4.4 mmol/l, and HR 1.26, 95% CI
      1.05-1.51 for TC above 5.1 mmol/l) and HDL in the highest tertile (HR 1.33, 95%
      CI 1.08-1.64) and above 1 mmol/l (HR 1.29, 95% CI 1.01-1.65). In contrast, TC in
      the highest tertile was associated with a decreased risk of PCa with 20-year lag
      time. The risk associations for overall PCa grew stronger with added lag time but
      were observed only in the FinRSPC control arm. Statin use did not modify the risk
      association. CONCLUSIONS: Hypercholesterolemia may increase overall PCa risk in
      short-term, inverse risk association was observed with 20-years' time lag.
      Similar risk increase of overall PCa was also observed for elevated HDL,
      conflicting with previous findings on the subject.

PMID- 30214036
TI  - Nocturia and associated mortality: observational data from the REDUCE trial.
AB  - BACKGROUND: Nocturia (voids arising from sleep) is a ubiquitous phenomenon
      reflecting many diverse conditions but whether it has significance in its own
      right remains uncertain. We examined whether nocturia was an independent risk
      factor for mortality METHODS: These were observational analyses employing
      primarily North American and European participants and included 7343 men, aged 50
      75 years participating in the REDUCE (Reduction by Dutasteride of Prostate Cancer
      Events) trial. Cox proportional hazards models were used to test the association
      between baseline nocturia (voiding >=3 times per night) and all-cause mortality.
      Potential confounding variables included: age; race; region of origin; treatment
      group; self-reported coronary artery disease, diabetes mellitus, hypertension,
      and peripheral vascular disease; smoking; alcohol use; prostate volume; and
      diuretics. Self-reported sleep quality, as measured with the Medical Outcomes
      Study sleep scale, was entered as a final step in the model. RESULTS: Nocturia
      was associated with increased mortality risk (hazard ratio [HR] = 1.72; 95% CI
      1.15-2.55) independent from demographics and medical comorbidities. Inclusion of
      disturbed sleep in the model reduced the magnitude of the association (HR = 1.43;
      95% CI 0.93-2.19). CONCLUSIONS: Although the findings are limited to men, half of
      whom ingested dutasteride, the interruption of sleep by nocturia may have long
      term impact on health and may warrant targeted intervention.

PMID- 30214035
TI  - Importance of androgen-deprivation therapy during enzalutamide treatment in men
      with metastatic castration-resistant prostate cancer following chemotherapy:
      results from retrospective, multicenter data.
AB  - BACKGROUND: Enzalutamide can significantly prolong the survival of patients with
      metastatic castration-resistant prostate cancer (mCRPC). However, there is a
      paucity of evidence on continuing androgen-deprivation therapy (ADT) for mCRPC.
      Here, we analyzed the effect of concomitant ADT during enzalutamide treatment in
      men with mCRPC following chemotherapy. METHODS: We retrospectively reviewed the
      medical records of 232 patients with mCRPC who received oral enzalutamide (160 mg
      per day) following chemotherapy at 9 tertiary centers in Korea between 2014 and
      2016. The primary endpoint was overall survival, while secondary endpoints
      included time to prostate-specific antigen (PSA) progression and radiographic
      progression-free survival. RESULTS: The median age of the patients was 71 years
      (interquartile range, 64-75 years). The proportion of patients in a grade group
      >=4 was 77.6%. The rate of concomitant ADT was 29.3%, and the all-cause mortality
      rate was 27.1% (n = 63). Median overall survival, time to PSA progression, and
      radiographic progression-free survival were 24.0, 8.0, and 10.0 months,
      respectively. Notably, concomitant ADT showed a significant association with
      longer overall survival (median duration not reached vs. 18.2 months; p = 0.008).
      After adjusting for confounding factors, concomitant ADT was still associated
      with longer overall survival (hazard ratio, 0.35; 95% confidence interval, 0.17
      0.72). CONCLUSION: Concomitant ADT during enzalutamide treatment may improve the
      survival of patients with mCRPC following chemotherapy.

PMID- 30214037
TI  - Senescence prevents regeneration after acute liver injury.

PMID- 30214038
TI  - Mechanisms by which gut microorganisms influence food sensitivities.
AB  - Finely tuned mechanisms enable the gastrointestinal tract to break down dietary
      components into nutrients without mounting, in the majority of cases, a
      dysregulated immune or functional host response. However, adverse reactions to
      food have been steadily increasing, and evidence suggests that this process is
      environmental. Adverse food reactions can be divided according to their
      underlying pathophysiology into food intolerances, when, for instance, there is
      deficiency of a host enzyme required to digest the food component, and food
      sensitivities, when immune mechanisms are involved. In this Review, we discuss
      the clinical and experimental evidence for enteric infections and/or alterations
      in the gut microbiota in inciting food sensitivity. We focus on mechanisms by
      which microorganisms might provide direct pro-inflammatory signals to the host
      promoting breakdown of oral tolerance to food antigens or indirect pathways that
      involve the metabolism of protein antigens and other dietary components by gut
      microorganisms. Better understanding of these mechanisms will help in the
      development of preventive and therapeutic strategies for food sensitivities.

PMID- 30214039
TI  - Increased macrophages and changed brain endothelial cell gene expression in the
      frontal cortex of people with schizophrenia displaying inflammation.
AB  - Elevated pro-inflammatory cytokines exist in both blood and brain of people with
      schizophrenia but how this affects molecular indices of the blood-brain barrier
      (BBB) is unclear. Eight mRNAs relating to BBB function, a microglia and three
      immune cell markers were measured by qPCR in the prefrontal cortex from 37 people
      with schizophrenia/schizoaffective disorder and 37 matched controls. This cohort
      was previously grouped into "high inflammation" and "low inflammation" subgroups
      based on cortical inflammatory-related transcripts. Soluble intercellular
      adhesion molecule-1 (sICAM1) was measured in the plasma of 78 patients with
      schizophrenia/schizoaffective disorder and 73 healthy controls. We found that
      sICAM1 was significantly elevated in schizophrenia. An efflux transporter, ABCG2,
      was lower, while mRNAs encoding VE-cadherin and ICAM1 were higher in
      schizophrenia brain. The "high inflammation" schizophrenia subgroup had lower
      ABCG2 and higher ICAM1, VE-cadherin, occludin and interferon-induced
      transmembrane protein mRNAs compared to both "low inflammation" schizophrenia and
      "low inflammation" control subgroups. ICAM1 immunohistochemistry showed
      enrichment in brain endothelium regardless of diagnosis and was localised to
      astrocytes in some brains. Microglia mRNA was not altered in schizophrenia nor
      did it correlate with ICAM1 expression. Immune cell mRNAs were elevated in "high
      inflammation" schizophrenia compared to both "low inflammation" schizophrenia and
      controls. CD163+ perivascular macrophages were identified by immunohistochemistry
      in brain parenchyma in over 40% of "high inflammation" schizophrenia brains.
      People with high levels of cytokine expression and schizophrenia display changes
      consistent with greater immune cell transmigration into brain via increased
      ICAM1, which could contribute to other neuropathological changes found in this
      subgroup of people.

PMID- 30214040
TI  - mGluR5 hypofunction is integral to glutamatergic dysregulation in schizophrenia.
AB  - Multiple lines of evidence point to glutamatergic signaling in the postsynaptic
      density (PSD) as a pathophysiologic mechanism in schizophrenia. Integral to PSD
      glutamatergic signaling is reciprocal interplay between GluN and mGluR5
      signaling. We examined agonist-induced mGluR5 signaling in the postmortem
      dorsolateral prefrontal cortex (DLPFC) derived from 17 patients and age-matched
      and sex-matched controls. The patient group showed a striking reduction in mGluR5
      signaling, manifested by decreases in Gq/11 coupling and association with PI3K
      and Homer compared to controls (p < 0.01 for all). This was accompanied by
      increases in serine and tyrosine phosphorylation of mGluR5, which can decrease
      mGluR5 activity via desensitization (p < 0.01). In addition, we find altered
      protein-protein interaction (PPI) of mGluR5 with RGS4, norbin, Preso 1 and
      tamalin, which can also attenuate mGluR5 activity. We previously reported
      molecular underpinnings of GluN hypofunction (decreased GluN2 phosphorylation)
      and here we show those of reduced mGluR5 signaling in schizophrenia. We find that
      reduced GluN2 phosphorylation can be precipitated by attenuated mGluR5 activity
      and that increased mGluR5 phosphorylation can result from decreased GluN
      function, suggesting a reciprocal interplay between the two pathways in
      schizophrenia. Interestingly, the patient group showed decreased mGluR5-GluN
      association (p < 0.01), a mechanistic basis for the reciprocal facilitation. In
      sum, we present the first direct evidence for mGluR5 hypoactivity, propose a
      reciprocal interplay between GluN and mGluR5 pathways as integral to
      glutamatergic dysregulation and suggest protein-protein interactions in mGluR5
      GluN complexes as potential targets for intervention in schizophrenia.

PMID- 30214041
TI  - Neuroimaging of reward mechanisms in Gambling disorder: an integrative review.
AB  - Gambling disorder (GD) was reclassified as a behavioral addiction in the DSM-5
      and shares clinical and behavioral features with substance use disorders (SUDs).
      Neuroimaging studies of GD hold promise in isolating core features of the
      addiction syndrome, avoiding confounding effects of drug neurotoxicity. At the
      same time, a neurobiologically-grounded theory of how behaviors like gambling can
      become addictive remains lacking, posing a significant hurdle for ongoing
      decisions in addiction nosology. This article integrates research on reward
      related brain activity (functional MRI) and neurotransmitter function (PET) in
      GD, alongside the consideration of structural MRI data as to whether these
      signals more likely reflect pre-existing vulnerability or neuroadaptive change.
      Where possible, we point to qualitative similarities and differences with
      established markers for SUDs. Structural MRI studies indicate modest changes in
      regional gray matter volume and diffuse reductions in white matter integrity in
      GD, contrasting with clear structural deterioration in SUDs. Functional MRI
      studies consistently identify dysregulation in reward-related circuitry
      (primarily ventral striatum and medial prefrontal cortex), but evidence is mixed
      as to the direction of these effects. The need for further parsing of reward sub
      processes is emphasized, including anticipation vs outcome, gains vs. losses, and
      disorder-relevant cues vs natural rewards. Neurotransmitter PET studies indicate
      amplified dopamine (DA) release in GD, in the context of minimal differences in
      baseline DA D2 receptor binding, highlighting a distinct profile from SUDs.
      Preliminary work has investigated further contributions of opioids, GABA and
      serotonin. Neuroimaging data increasingly highlight divergent profiles in GD vs.
      SUDs. The ability of gambling to perpetually activate DA (via maximal
      uncertainty) may contribute to neuroimaging similarities between GD and SUDs,
      whereas the supra-physiological DA effects of drugs may partly explain
      differences in the neuroimaging profile of the two syndromes. Coupled with
      consistent observations of correlations with gambling severity and related
      clinical variables within GD samples, the overall pattern of effects is
      interpreted as a likely combination of shared vulnerability markers across GD and
      SUDs, but with further experience-dependent neuroadaptive processes in GD.

PMID- 30214043
TI  - Genetic identification of a population of noradrenergic neurons implicated in
      attenuation of stress-related responses.
AB  - Noradrenergic signaling plays a well-established role in promoting the stress
      response. Here we identify a subpopulation of noradrenergic neurons, defined by
      developmental expression of Hoxb1, that has a unique role in modulating stress
      related behavior. Using an intersectional chemogenetic strategy, in combination
      with behavioral and physiological analyses, we show that activation of Hoxb1
      noradrenergic (Hoxb1-NE) neurons decreases anxiety-like behavior and promotes an
      active coping strategy in response to acute stressors. In addition, we use
      cerebral blood volume-weighted functional magnetic resonance imaging to show that
      chemoactivation of Hoxb1-NE neurons results in reduced activity in stress-related
      brain regions, including the bed nucleus of the stria terminalis, amygdala, and
      locus coeruleus. Thus, the actions of Hoxb1-NE neurons are distinct from the well
      documented functions of the locus coeruleus in promoting the stress response,
      demonstrating that the noradrenergic system contains multiple functionally
      distinct subpopulations.

PMID- 30214042
TI  - Neurotransmitter changes after traumatic brain injury: an update for new
      treatment strategies.
AB  - Traumatic brain injury (TBI) is a pervasive problem in the United States and
      worldwide, as the number of diagnosed individuals is increasing yearly and there
      are no efficacious therapeutic interventions. A large number of patients suffer
      with cognitive disabilities and psychiatric conditions after TBI, especially
      anxiety and depression. The constellation of post-injury cognitive and behavioral
      symptoms suggest permanent effects of injury on neurotransmission. Guided in part
      by preclinical studies, clinical trials have focused on high-yield
      pathophysiologic mechanisms, including protein aggregation, inflammation,
      metabolic disruption, cell generation, physiology, and alterations in
      neurotransmitter signaling. Despite successful treatment of experimental TBI in
      animal models, clinical studies based on these findings have failed to translate
      to humans. The current international effort to reshape TBI research is focusing
      on redefining the taxonomy and characterization of TBI. In addition, as the next
      round of clinical trials is pending, there is a pressing need to consider what
      the field has learned over the past two decades of research, and how we can best
      capitalize on this knowledge to inform the hypotheses for future innovations.
      Thus, it is critically important to extend our understanding of the
      pathophysiology of TBI, particularly to mechanisms that are associated with
      recovery versus development of chronic symptoms. In this review, we focus on the
      pathology of neurotransmission after TBI, reflecting on what has been learned
      from both the preclinical and clinical studies, and we discuss new directions and
      opportunities for future work.

PMID- 30214044
TI  - Ant1 mutant mice bridge the mitochondrial and serotonergic dysfunctions in
      bipolar disorder.

PMID- 30214045
TI  - Linking unfolded protein response to inflammation and depression: potential
      pathologic and therapeutic implications.
AB  - Depression is a devastating mental disorder that affects millions of people
      worldwide. Inflammation has been shown to be a key factor involved in the
      underlying pathophysiology of depression and has been shown in a substantial
      proportion of cases of depression. Changes attributed with morphological
      deformities and immunomodulation in susceptible regions of the depressed brain
      raised the possibility of altered cellular homeostasis transduced by the
      intracellular stress response. How emotional stressors can lead to an inflamed
      brain that directly affects physiology and activity is yet to be fully
      understood. The unfolded protein response (UPR) has been shown to be active in
      both models of depression as well as in postmortem brain of depressed
      individuals. The UPR is the cellular response to stress which results in
      misfolded proteins. Interestingly, UPR activation is directly linked to both
      inflammatory cytokine production and Toll-like receptor (TLR) expression. The
      TLRs are part of the innate immune response which typically reacts to "classic
      invasions" such as bacteria or viruses as well as trauma. TLRs have also been
      shown to be upregulated in depression, thus solidifying the connection between
      inflammation and depression. In this review, we aim to tie the UPR-TLR response
      and depression, and describe the implications of such an association. We also
      propose future directions for their role in treatment for depression.

PMID- 30214046
TI  - Alcohol and dementia - risk or protective factor?

PMID- 30214047
TI  - Therapeutic potential for peripheral clearance of misfolded brain proteins.

PMID- 30214048
TI  - Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of
      PPARgamma2.
AB  - Understanding the epigenetic mechanisms underlying the progression of hepatic
      steatosis is important for identifying new therapeutic targets against
      nonalcoholic fatty liver disease (NAFLD). We investigated the functional role of
      histone demethylase JMJD2B in the pathologic regulation of hepatic steatosis.
      JMJD2B expression was markedly increased in HepG2 cells treated with palmitate
      and oleate or liver X receptor agonist T09013178 and in the liver of high-fat
      diet (HFD)-induced obese mice. Overexpression of JMJD2B using adenovirus in HepG2
      cells stimulated the expression of peroxisome proliferator-activated receptor
      gamma2 (PPARgamma2) and its steatosis target genes associated with fatty acid
      uptake and lipid droplet formation, resulting in increased intracellular
      triglyceride (TG) accumulation. Conversely, knocking down JMJD2B using siRNA
      reversed JMJD2B-mediated effects in HepG2 cells. The JMJD2B-dependent
      upregulation of PPARgamma2 was associated with the removal of di- and
      trimethylation of histone H3 lysine 9 on the promoter of PPARgamma2. Furthermore,
      exogeneous expression of JMJD2B using adenovirus in mice resulted in hepatic
      steatosis when fed a HFD, which was accompanied with increased expression of
      hepatic PPARgamma2 and its steatosis target genes. Together, our results provide
      novel insights into the pivotal role of JMJD2B in the development of hepatic
      steatosis through upregulation of PPARgamma2 and steatosis target genes.

PMID- 30214049
TI  - Spinning-disc confocal microscopy in the second near-infrared window (NIR-II).
AB  - Fluorescence microscopy in the second near-infrared optical window (NIR-II, 1000
      1350 nm) has become a technique of choice for non-invasive in vivo imaging. The
      deep penetration of NIR light in living tissue, as well as negligible tissue
      autofluorescence within this optical range, offers increased resolution and
      contrast with even greater penetration depths. Here, we present a custom-built
      spinning-disc confocal laser microscope (SDCLM) that is specific to imaging in
      the NIR-II. The SDCLM achieves a lateral resolution of 0.5 +/- 0.1 um and an
      axial resolution of 0.6 +/- 0.1 um, showing a ~17% and ~45% enhancement in
      lateral and axial resolution, respectively, compared to the corresponding wide
      field configuration. We furthermore showcase several applications that
      demonstrate the use of the SDCLM for in situ, spatiotemporal tracking of NIR
      particles and bioanalytes within both synthetic and biological systems.

PMID- 30214050
TI  - Altering Compliance of a Load Carriage Device in the Medial-Lateral Direction
      Reduces Peak Forces While Walking.
AB  - Altering mechanical compliance in load carriage structures has shown to reduce
      metabolic cost and accelerative forces of carrying weight. Currently,
      modifications to load carriage structures have been primarily targeted at
      vertical motion of the carried mass. No study to date has investigated altering
      load carriage compliance in the medial-lateral direction. We developed a backpack
      specifically for allowing a carried mass to oscillate in the horizontal
      direction, giving us the unique opportunity to understand the effects of lateral
      mass motion on human gait. Previous modelling work has shown that walking economy
      can be improved through the interaction of a bipedal model with a laterally
      oscillating walking surface. To test whether a laterally oscillating mass can
      experimentally improve walking economy, we systematically varied step width above
      and below the preferred level and compared the effects of carrying an oscillating
      and fixed mass. Walking with an oscillating mass was found to reduce the
      accelerative forces of load carriage in both horizontal and vertical directions.
      However, load eccentricity caused the vertical force component to create a
      significant bending moment in the frontal plane. Walking with an oscillating mass
      led to an increase in the metabolic energy expenditure during walking and an
      increase in positive hip work during stance. The device's ability to reduce
      forces experienced by the user, due to load carriage, holds promise. However, the
      requirement of additional metabolic energy to walk with the device requires
      future study to improve.

PMID- 30214051
TI  - High-Reynolds Microfluidic Sorting of Large Yeast Populations.
AB  - Microfluidic sorting offers a unique ability to isolate large numbers of cells
      for bulk proteomic or metabolomics studies but is currently limited by low
      throughput and persistent clogging at low flow rates. Recently we uncovered the
      physical principles governing the inertial focusing of particles in high-Reynolds
      numbers. Here, we superimpose high Reynolds inertial focusing on Dean vortices,
      to rapidly isolate large quantities of young and adult yeast from mixed
      populations at a rate of 107 cells/min/channel. Using a new algorithm to rapidly
      quantify budding scars in isolated yeast populations and system-wide proteomic
      analysis, we demonstrate that protein quality control and expression of
      established yeast aging markers such as CalM, RPL5, and SAM1 may change after the
      very first replication events, rather than later in the aging process as
      previously thought. Our technique enables the large-scale isolation of
      microorganisms based on minute differences in size (+/-1.5 MUm), a feat unmatched
      by other technologies.

PMID- 30214052
TI  - Innovative Biocatalysts as Tools to Detect and Inactivate Nerve Agents.
AB  - Pesticides and warfare nerve agents are frequently organophosphates (OPs) or
      related compounds. Their acute toxicity highlighted more than ever the need to
      explore applicable strategies for the sensing, decontamination and/or
      detoxification of these compounds. Herein, we report the use of two different
      thermostable enzyme families capable to detect and inactivate OPs. In particular,
      mutants of carboxylesterase-2 from Alicyclobacillus acidocaldarius and of
      phosphotriesterase-like lactonases from Sulfolobus solfataricus and Sulfolobus
      acidocaldarius, have been selected and assembled in an optimized format for the
      development of an electrochemical biosensor and a decontamination formulation,
      respectively. The features of the developed tools have been tested in an ad-hoc
      fabricated chamber, to mimic an alarming situation of exposure to a nerve agent.
      Choosing ethyl-paraoxon as nerve agent simulant, a limit of detection (LOD) of
      0.4 nM, after 5 s of exposure time was obtained. Furthermore, an optimized
      enzymatic formulation was used for a fast and efficient environmental
      detoxification (>99%) of the nebulized nerve agent simulants in the air and on
      surfaces. Crucial, large-scale experiments have been possible thanks to
      production of grams amounts of pure (>90%) enzymes.

PMID- 30214053
TI  - High-performance flexible metal-on-silicon thermocouple.
AB  - We have demonstrated metal-on-silicon thermocouples with a noticeably high
      Seebeck coefficient and an excellent temperature-sensing resolution. Fabrication
      of the thermocouples involved only simple photolithography and metal-liftoff
      procedures on a silicon substrate. The experimentally measured Seebeck
      coefficient of our thermocouple was 9.17 * 10-4 V/ degrees K, which is 30 times
      larger than those reported for standard metal thin-film thermocouples and
      comparable to the values of alloy-based thin-film thermocouples that require
      sophisticated and costly fabrication processes. The temperature-voltage
      measurements between 20 to 80  degrees C were highly linear with a linearity
      coefficient of 1, and the experimentally demonstrated temperature-sensing
      resolution was 0.01  degrees K which could be further improved up to a
      theoretical limit of 0.00055  degrees K. Finally, we applied this approach to
      demonstrate a flexible metal-on-silicon thermocouple with enhanced thermal
      sensitivity. The outstanding performance of our thermocouple combined with an
      extremely thin profile, bending flexibility, and simple, highly-compatible
      fabrication will proliferate its use in diverse applications such as micro
      /nanoscale biometrics, energy management, and nanoscale thermography.

PMID- 30214054
TI  - Mesenchymal stem cells and the embryonic reawakening theory of BPH.
AB  - The prostate is the only organ in a man that continues to grow with age. John
      McNeal proposed, 40 years ago, that this BPH is characterized by an age-related
      reinitiation of benign neoplastic growth selectively in developmentally abortive
      distal ducts within the prostate transition-periurethral zone (TPZ), owing to a
      reawakening of inductive stroma selectively within these zones. An innovative
      variant of this hypothesis is that, owing to its location, the TPZ is
      continuously exposed to urinary components and/or autoantigens, which produces an
      inflammatory TPZ microenvironment that promotes recruitment of bone marrow
      derived mesenchymal stem cells (MSCs) and generates a paracrine-inductive stroma
      that reinitiates benign neoplastic nodular growth. In support of this hypothesis,
      MSCs infiltrate human BPH tissue and have the ability to stimulate epithelial
      stem cell growth. These results provide a framework for defining both the
      aetiology of BPH in ageing men and insights into new therapeutic approaches.

PMID- 30214055
TI  - Establishment of a modified CRISPR/Cas9 system with increased mutagenesis
      frequency using the translational enhancer dMac3 and multiple guide RNAs in
      potato.
AB  - CRISPR/Cas9 is a programmable nuclease composed of the Cas9 protein and a guide
      RNA (gRNA) molecule. To create a mutant potato, a powerful genome-editing system
      was required because potato has a tetraploid genome. The translational enhancer
      dMac3, consisting of a portion of the OsMac3 mRNA 5'-untranslated region, greatly
      enhanced the production of the protein encoded in the downstream ORF. To enrich
      the amount of Cas9, we applied the dMac3 translational enhancer to the Cas9
      expression system with multiple gRNA genes. CRISPR/Cas9 systems targeting the
      potato granule-bound starch synthase I (GBSSI) gene examined the frequency of
      mutant alleles in transgenic potato plants. The efficiency of the targeted
      mutagenesis strongly increased when the dMac3-installed Cas9 was used. In this
      case, the ratio of transformants containing four mutant alleles reached
      approximately 25% when estimated by CAPS analysis. The mutants that exhibited
      targeted mutagenesis in the GBSSI gene showed characteristics of low amylose
      starch in their tubers. This result suggests that our system may facilitate
      genome-editing events in polyploid plants.

PMID- 30214056
TI  - Low survival of strongly footed pheasants may explain constraints on
      lateralization.
AB  - Brain lateralization is considered adaptive because it leads to behavioral biases
      and specializations that bring fitness benefits. Across species, strongly
      lateralized individuals perform better in specific behaviors likely to improve
      survival. What constrains continued exaggerated lateralization? We measured
      survival of pheasants, finding that individuals with stronger bias in their
      footedness had shorter life expectancies compared to individuals with weak
      biases. Consequently, weak, or no footedness provided the highest fitness
      benefits. If, as suggested, footedness is indicative of more general brain
      lateralization, this could explain why continued brain lateralization is
      constrained even though it may improve performance in specific behaviors.

PMID- 30214057
TI  - Identifying weak interdomain interactions that stabilize the supertertiary
      structure of the N-terminal tandem PDZ domains of PSD-95.
AB  - Previous studies of the N-terminal PDZ tandem from PSD-95 produced divergent
      models and failed to identify interdomain contacts stabilizing the structure. We
      used ensemble and single-molecule FRET along with replica-exchange molecular
      dynamics to fully characterize the energy landscape. Simulations and experiments
      identified two conformations: an open-like conformation with a small contact
      interface stabilized by salt bridges, and a closed-like conformation with a
      larger contact interface stabilized by surface-exposed hydrophobic residues. Both
      interfaces were confirmed experimentally. Proximity of interdomain contacts to
      the binding pockets may explain the observed coupling between conformation and
      binding. The low-energy barrier between conformations allows submillisecond
      dynamics, which were time-averaged in previous NMR and FRET studies. Moreover,
      the small contact interfaces were likely overridden by lattice contacts as
      crystal structures were rarely sampled in simulations. Our hybrid approach can
      identify transient interdomain interactions, which are abundant in multidomain
      proteins yet often obscured by dynamic averaging.

PMID- 30214059
TI  - NMDA-receptor independent actions of ketamine: a new chapter in a story that's
      not so old.

PMID- 30214060
TI  - Motion mapping in humans as a biomarker for psychiatric disorders.

PMID- 30214058
TI  - Sex differences in hippocampal cognition and neurogenesis.
AB  - Sex differences are reported in hippocampal plasticity, cognition, and in a
      number of disorders that target the integrity of the hippocampus. For example,
      meta-analyses reveal that males outperform females on hippocampus-dependent tasks
      in rodents and in humans, furthermore women are more likely to experience greater
      cognitive decline in Alzheimer's disease and depression, both diseases
      characterized by hippocampal dysfunction. The hippocampus is a highly plastic
      structure, important for processing higher order information and is sensitive to
      the environmental factors such as stress. The structure retains the ability to
      produce new neurons and this process plays an important role in pattern
      separation, proactive interference, and cognitive flexibility. Intriguingly,
      there are prominent sex differences in the level of neurogenesis and the
      activation of new neurons in response to hippocampus-dependent cognitive tasks in
      rodents. However, sex differences in spatial performance can be nuanced as animal
      studies have demonstrated that there are task, and strategy choice dependent sex
      differences in performance, as well as sex differences in the subregions of the
      hippocampus influenced by learning. This review discusses sex differences in
      pattern separation, pattern completion, spatial learning, and links between adult
      neurogenesis and these cognitive functions of the hippocampus. We emphasize the
      importance of including both sexes when studying genomic, cellular, and
      structural mechanisms of the hippocampal function.

PMID- 30214061
TI  - Structural characterization of a novel KH-domain containing plant chloroplast
      endonuclease.
AB  - Chlamydomonas reinhardtii is a single celled alga that undergoes apoptosis in
      response to UV-C irradiation. UVI31+, a novel UV-inducible DNA endonuclease in C.
      reinhardtii, which normally localizes near cell wall and pyrenoid regions, gets
      redistributed into punctate foci within the whole chloroplast, away from the
      pyrenoid, upon UV-stress. Solution NMR structure of the first putative UV
      inducible endonuclease UVI31+ revealed an alpha1-beta1-beta2-alpha2-alpha3-beta3
      fold similar to BolA and type II KH-domain ubiquitous protein families. Three
      alpha-helices of UVI31+ constitute one side of the protein surface, which are
      packed to the other side, made of three-stranded beta-sheet, with intervening
      hydrophobic residues. A twenty-three residues long polypeptide stretch (D54-H76)
      connecting beta1 and beta2 strands is found to be highly flexible. Interestingly,
      UVI31+ recognizes the DNA primarily through its beta-sheet. We propose that the
      catalytic triad residues involving Ser114, His95 and Thr116 facilitate DNA
      endonuclease activity of UVI31+. Further, decreased endonuclease activity of the
      S114A mutant is consistent with the direct participation of Ser114 in the
      catalysis. This study provides the first structural description of a plant
      chloroplast endonuclease that is regulated by UV-stress response.

PMID- 30214062
TI  - Behavioral performance and visual strategies during skill acquisition using a
      novel tool use motor learning task.
AB  - Habitual tool use is considered a hallmark of human evolution. One potential
      explanation for humanity's advanced tool using abilities is that humans possess a
      unique neurobiological system that estimates efficient ways to manipulate objects
      with novel tools, resulting in rapid tool use motor learning. However, since
      humans regularly use a multitude of tools, examining these underlying processes
      is challenging. As such, we developed a tool use motor learning paradigm that
      utilizes a challenging tool (chopsticks) in order to accomplish a difficult
      behavioral task that requires extensive practice to continuously improve one's
      proficiency. We then assessed the paradigm by recruiting participants with little
      experience using chopsticks and training them over the course of eight training
      sessions to grasp marbles with chopsticks and drop them in a cylindrical
      container. Throughout training, we examined behavioral performance and visual
      strategies to determine whether practicing the task resulted in outcomes
      congruent with traditional motor learning. Results show that performance
      increases in a logarithmic pattern and is accompanied by decreased confirmatory
      visual strategies. Since these findings are congruent with those seen in
      traditional motor learning, this paradigm is a novel method for use in future
      research examining the underlying mechanisms that mediate tool use motor
      learning.

PMID- 30214064
TI  - Increasing genomic literacy among adolescents.
AB  - PURPOSE: Adolescents increasingly need to be "genomics literate," and may engage
      more with video educational formats than traditional written formats. We
      conducted a pilot study to assess and compare the impact of two modes of
      education about genome sequencing (GS) on adolescents' genomic knowledge and
      genomic-related decisions. METHODS: Using an online survey, 43 adolescents ages
      14-17 years were randomly assigned to watch a video or read a pamphlet about GS.
      Measures included pre- and postintervention assessment of genomic knowledge,
      perceived utility of these materials for decisions about participating in genetic
      research, interest in receiving GS results, and overall satisfaction with these
      materials. Analyses described results for all participants and compared results
      between intervention groups. RESULTS: Self-reported genomic knowledge increased
      overall (p < 0.001). Postintervention knowledge about GS limitations was higher
      among video group than pamphlet group participants (p = 0.038). More video group
      than pamphlet group participants expressed satisfaction with the material's
      understandability (45% vs. 29%) and suitability (91% vs. 76%). Interest in
      receiving personal GS results was significantly associated with being female (p =
      0.01) and younger (14-15 years vs. 16-17 years) (p = 0.002). CONCLUSION: A video
      format may be preferable for increasing genomic literacy among adolescents.
      Further research with adolescents is needed to better understand how gender and
      age may impact genomic decisions and preferences.

PMID- 30214063
TI  - Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel
      therapeutic drug for AML with high EVI1 expression.
AB  - G protein-coupled receptor 56 (GPR56) is highly expressed in acute myeloid
      leukemia (AML) cells with high EVI1 expression (EVI1high AML). Because GPR56 is a
      transcriptional target of EVI1 and silencing of GPR56 expression induces
      apoptosis, we developed a novel drug to suppress GPR56 expression in EVI1high AML
      cells. For this purpose, we generated pyrrole-imidazole (PI) polyamides specific
      to GPR56 (PIP/56-1 or PIP/56-2) as nuclease-resistant novel compounds that
      interfere with the binding of EVI1 to the GPR56 promoter in a sequence-specific
      manner. Treatment of EVI1high AML cell lines (UCSD/AML1 and Kasumi-3) with PIP/56
      1 or PIP/56-2 effectively suppressed GPR56 expression by inhibiting binding of
      EVI1 to its promoter, leading to suppression of cell growth with increased rates
      of apoptosis. Moreover, intravenous administration of PIP/56-1 into
      immunodeficient Balb/c-RJ mice subcutaneously transplanted with UCSD/AML1 cells
      significantly inhibited tumor growth and extended survival. Furthermore, organ
      infiltration by leukemia cells in immunodeficient Balb/c-RJ mice, which were
      intravenously transplanted using UCSD/AML1 cells, was successfully inhibited by
      PIP/56-1 treatment with no apparent effects on murine hematopoietic cells. In
      addition, PIP treatment did not inhibit colony formation of human CD34+
      progenitor cells. Thus, PI polyamide targeting of GPR56 using our compound is
      promising, useful, and safe for the treatment of EVI1high AML.

PMID- 30214065
TI  - The physician-patient relationship in the age of precision medicine.

PMID- 30214066
TI  - Use of a novel computerized decision aid for aneuploidy screening: a randomized
      controlled trial.
AB  - PURPOSE: To assess whether knowledge following use of a decision aid (DA) for
      aneuploidy screening and testing is inferior to knowledge in women who saw a
      genetic counselor (GC) only. METHODS: This is a randomized controlled
      noninferiority trial of pregnant women at <=22 weeks. Women who were scheduled
      for GC were randomly allocated to use a DA before GC or to GC alone. The primary
      outcome was knowledge score, comparing women who had used the DA only to those
      who saw GC alone. Analysis was by intent to treat. RESULTS: Between January and
      October 2017, 197 women were randomized, 105 to GC only and 92 to DA use before
      GC. Demographics and baseline knowledge were similar between groups. Mean
      knowledge score following DA use was not inferior to mean knowledge score
      following GC only (10.4 vs. 10.6, p = 0.306). Decisional conflict was similar
      following completion of the DA to following GC only, but was reduced following
      completion of both the DA and GC compared with GC only (0.22 vs. 1.74, p =
      0.003). CONCLUSION: Knowledge surrounding aneuploidy screening in women who used
      a DA was not inferior to knowledge in women who underwent GC. Use of the DA in
      addition to GC reduced decisional conflict.

PMID- 30214067
TI  - Frequency and signature of somatic variants in 1461 human brain exomes.
AB  - PURPOSE: To systematically study somatic variants arising during development in
      the human brain across a spectrum of neurodegenerative disorders. METHODS: In
      this study we developed a pipeline to identify somatic variants from exome
      sequencing data in 1461 diseased and control human brains. Eighty-eight percent
      of the DNA samples were extracted from the cerebellum. Identified somatic
      variants were validated by targeted amplicon sequencing and/or PyroMark(r) Q24.
      RESULTS: We observed somatic coding variants present in >10% of sampled cells in
      at least 1% of brains. The mutational signature of the detected variants showed a
      predominance of C>T variants most consistent with arising from DNA mismatch
      repair, occurred frequently in genes that are highly expressed within the central
      nervous system, and with a minimum somatic mutation rate of 4.25 * 10-10 per base
      pair per individual. CONCLUSION: These findings provide proof-of-principle that
      deleterious somatic variants can affect sizeable brain regions in at least 1% of
      the population, and thus have the potential to contribute to the pathogenesis of
      common neurodegenerative diseases.

PMID- 30214069
TI  - CFTR variants and renal abnormalities in males with congenital unilateral absence
      of the vas deferens (CUAVD): a systematic review and meta-analysis of
      observational studies.
AB  - PURPOSE: CFTR variant is the main genetic contributor to congenital
      (unilateral/bilateral) absence of the vas deferens (CAVD/CUAVD/CBAVD). We
      performed a systematic review to elucidate the genetic link between CFTR
      variants, CUAVD, and the associated risk of renal abnormality (RA). METHODS: We
      searched relevant databases for eligible articles reporting CFTR variants in
      CUAVD. The frequency of CFTR variants and RA, and the odds ratios (ORs) for
      common alleles and RA risk, were pooled under random-/fixed-effect models.
      Subgroup analyses and heterogeneity tests were performed. RESULTS: Twenty-three
      studies were included. Among CUAVD patients, 46% had at least one CFTR variant,
      with 27% having one and 5% having two. The allele frequency in CUAVD was 4% for
      F508del and 9% for 5T. The summary OR for 5T risk in CUAVD was 5.79 compared with
      normal controls and 2.82 compared with non-CAVD infertile males. The overall
      incidence of RA was 22% in CUAVD. The pooled OR for RA risk among CUAVD patients
      was 4.85 compared with CBAVD patients. CONCLUSION: CFTR variants are common in
      CUAVD, and the 5T allele may be associated with increased CUAVD risk. CUAVD
      patients bear a higher RA risk than CBAVD patients, but this is not associated
      with CFTR variants.

PMID- 30214068
TI  - Misattributed parentage as an unanticipated finding during exome/genome
      sequencing: current clinical laboratory practices and an opportunity for
      standardization.
AB  - PURPOSE: Clinical laboratories performing exome or genome sequencing (ES/GS) are
      familiar with the challenges associated with proper consenting for and reporting
      of medically actionable secondary findings based on recommendations from the
      American College of Medical Genetics and Genomics (ACMG). Misattributed parentage
      is another type of unanticipated finding a laboratory may encounter during family
      based ES/GS; however, there are currently no professional recommendations related
      to the proper consenting for and reporting of misattributed parentage encountered
      during ES/GS. METHODS: We surveyed 10 clinical laboratories offering family-based
      ES/GS regarding their consent language, discovery, and reporting of misattributed
      parentage. RESULTS: Many laboratories have already developed their own
      practices/policies for these issues, which do not necessarily agree with those
      from other labs. CONCLUSION: There are several other possibilities besides true
      misattributed parentage that could result in similar laboratory findings, and
      laboratories often feel they lack sufficient information to make formal
      conclusions on a report regarding the true genetic relatedness of the submitted
      samples. However, understanding the genetic relatedness (or lack thereof) of the
      samples submitted for family-based ES/GS has medical relevance. Therefore,
      professional recommendations for the appropriate handling of suspected
      misattributed parentage encountered during ES/GS are needed to help standardize
      current clinical laboratory practices.

PMID- 30214070
TI  - Developing a genetic services assessment tool to inform quality improvement
      efforts in state genetic service delivery.
AB  - PURPOSE: The Institute of Medicine recommended the utilization of metrics to
      improve quality in health care, although they have rarely been used in genetics.
      This study developed and tested a set of metrics for a quality assessment tool
      for genetic services METHODS: A systematic review of literature, guidelines, and
      consensus statements identified candidate measures for a possible assessment
      tool. An expert panel conducted a modified Delphi technique to rank the metrics.
      Ratings were computed to generate a score for each metric, creating a set of
      metrics for consensus discussions, pilot testing, and feasibility testing in
      eight Midwestern states. RESULTS: The panel reduced 61 candidate metrics to 21
      for pilot testing in two states, which further limited and refined the set to 16
      metrics. These 16 were categorized into five domains: service capacity, access to
      care, data systems, performance reporting, and workforce. Further feasibility
      testing in one Regional Genetics Collaborative identified the tool's usefulness
      and barriers to implementation. CONCLUSIONS: These quality metrics for both
      clinical and public health genetics across the lifespan may help medical
      professionals and policymakers evaluate quality and cost-effectiveness of genetic
      services on a statewide basis and stimulate outcome-oriented, health services
      research in medical genetics and genomics.

PMID- 30214071
TI  - Genomic and phenotypic delineation of congenital microcephaly.
AB  - PURPOSE: Congenital microcephaly (CM) is an important birth defect with long term
      neurological sequelae. We aimed to perform detailed phenotypic and genomic
      analysis of patients with Mendelian forms of CM. METHODS: Clinical phenotyping,
      targeted or exome sequencing, and autozygome analysis. RESULTS: We describe 150
      patients (104 families) with 56 Mendelian forms of CM. Our data show little
      overlap with the genetic causes of postnatal microcephaly. We also show that a
      broad definition of primary microcephaly -as an autosomal recessive form of
      nonsyndromic CM with severe postnatal deceleration of occipitofrontal
      circumference-is highly sensitive but has a limited specificity. In addition, we
      expand the overlap between primary microcephaly and microcephalic primordial
      dwarfism both clinically (short stature in >52% of patients with primary
      microcephaly) and molecularly (e.g., we report the first instance of CEP135
      related microcephalic primordial dwarfism). We expand the allelic and locus
      heterogeneity of CM by reporting 37 novel likely disease-causing variants in 27
      disease genes, confirming the candidacy of ANKLE2, YARS, FRMD4A, and THG1L, and
      proposing the candidacy of BPTF, MAP1B, CCNH, and PPFIBP1. CONCLUSION: Our study
      refines the phenotype of CM, expands its genetics heterogeneity, and informs the
      workup of children born with this developmental brain defect.

PMID- 30214072
TI  - An immune tolerance approach using transient low-dose methotrexate in the ERT
      naive setting of patients treated with a therapeutic protein: experience in
      infantile-onset Pompe disease.
AB  - PURPOSE: To investigate immune tolerance induction with transient low-dose
      methotrexate (TLD-MTX) initiated with recombinant human acid alpha-glucosidase
      (rhGAA), in treatment-naive cross-reactive immunologic material (CRIM)-positive
      infantile-onset Pompe disease (IOPD) patients. METHODS: Newly diagnosed IOPD
      patients received subcutaneous or oral 0.4 mg/kg TLD-MTX for 3 cycles (3
      doses/cycle) with the first 3 rhGAA infusions. Anti-rhGAA IgG titers, classified
      as high-sustained (HSAT; >=51,200, >=2 times after 6 months), sustained
      intermediate (SIT; >=12,800 and <51,200 within 12 months), or low (LT; <=6400
      within 12 months), were compared with those of 37 CRIM-positive IOPD historic
      comparators receiving rhGAA alone. RESULTS: Fourteen IOPD TLD-MTX recipients at
      the median age of 3.8 months (range, 0.7-13.5 months) had a median last titer of
      150 (range, 0-51,200) at median rhGAA duration ~83 weeks (range, 36-122 weeks).
      One IOPD patient (7.1%) developed titers in the SIT range and one patient (7.1%)
      developed titers in the HSAT range. Twelve of the 14 patients (85.7%) that
      received TLD-MTX remained LT, versus 5/37 HSAT (peak 51,200-409,600), 7/37 SIT
      (12,800-51,000), and 23/37 LT (200-12,800) among comparators. CONCLUSION: Results
      of TLD-MTX coinitiated with rhGAA are encouraging and merit a larger longitudinal
      study.

PMID- 30214076
TI  - The ultimate guide to restoration longevity in England and Wales. Part 6: molar
      teeth: restoration time to next intervention and to extraction of the restored
      tooth.

PMID- 30214074
TI  - Missense mutation of VKORC1 leads to medial arterial calcification in rats.
AB  - Vitamin K plays a crucial role in the regulation of vascular calcifications by
      allowing activation of matrix Gla protein. The dietary requirement for vitamin K
      is low because of an efficient recycling of vitamin K by vitamin K epoxide
      reductase (VKORC1). However, decreased VKORC1 activity may result in vascular
      calcification. More than 30 coding mutations of VKORC1 have been described. While
      these mutations have been suspected of causing anticoagulant resistance, their
      association with an increase in the risk of vascular calcification has never been
      considered. We thus investigated functional cardiovascular characteristics in a
      rat model mutated in VKORC1. This study revealed that limited intake in vitamin K
      in mutated rat induced massive calcified areas in the media of arteries of lung,
      aortic arch, kidneys and testis. Development of calcifications could be inhibited
      by vitamin K supplementation. In calcified areas, inactive Matrix Gla protein
      expression increased, while corresponding mRNA expression was not modified.
      Mutation in VKORC1 associated with a limited vitamin K intake is thus a major
      risk for cardiovascular disease. Our model is the first non-invasive rat model
      that shows spontaneous medial calcifications and would be useful for studying
      physiological function of vitamin K.

PMID- 30214075
TI  - Exploration of ligand binding modes towards the identification of compounds
      targeting HuR: a combined STD-NMR and Molecular Modelling approach.
AB  - Post-transcriptional processes have been recognised as pivotal in the control of
      gene expression, and impairments in RNA processing are reported in several
      pathologies (i.e., cancer and neurodegeneration). Focusing on RNA-binding
      proteins (RBPs), the involvement of Embryonic Lethal Abnormal Vision (ELAV) or Hu
      proteins and their complexes with target mRNAs in the aetiology of various
      dysfunctions, has suggested the great potential of compounds able to interfere
      with the complex stability as an innovative pharmacological strategy for the
      treatment of numerous diseases. Here, we present a rational follow-up
      investigation of the interaction between ELAV isoform HuR and structurally
      related compounds (i.e., flavonoids and coumarins), naturally decorated with
      different functional groups, by means of STD-NMR and Molecular Modelling. Our
      results represent the foundation for the development of potent and selective
      ligands able to interfere with ELAV-RNA complexes.

PMID- 30214077
TI  - Midterm outcomes of mini-invasive surgical and hybrid ablation of atrial
      fibrillation.
AB  - BACKGROUND: We evaluated the feasibility and effectiveness of thoracoscopic and a
      staged surgical and transcatheter ablation technique to treat stand-alone atrial
      fibrillation (AF). METHODS: . Between 2009 and 2016, a cohort of 65 patients
      underwent bilateral totally thoracoscopic ablation of symptomatic paroxysmal AF
      (n=30; 46%), persistent AF (n=18; 28%) or long-standing persistent AF (n=17; 26%)
      followed by catheter ablation in case of AF recurrence. Surgical box lesion
      procedure included bilateral pulmonary vein and left atrial posterior wall
      ablation using irrigated bipolar radiofrequency with documentation of conduction
      block. RESULTS: There were no intra- or peri-operative ablation-related
      complications. There was no operative mortality, no myocardial infarction, and no
      stroke. Skin-to-skin procedure time was 120.5 +/- 22.0 min and the postoperative
      average length of stay was 8.1 +/- 3.0 days. At discharge, 60 patients (92%) were
      in sinus rhythm. Median follow-up time was 866 days (IQR, 612-1185 days). One
      year success rate after surgical procedure was 78% (off antiarrhythmic drugs).
      Eleven patients (17%) underwent catheter re-ablation. Sixty (92%) patients were
      free of atrial fibrillation after hybrid ablation (on demand) at 1 year follow up
      after the last ablation. The success at 24-months was achieved in 96%
      (paroxysmal) and 78% (persistent) patients. At the last follow-up control, 69%
      patients discontinued oral anticoagulant therapy. CONCLUSIONS: . Combination of
      mini-invasive surgical and endocardial treatment (two-stage hybrid procedure) is
      a safe and effective method for the treatment of isolated (lone) AF. This
      procedure provided good midterm outcomes.

PMID- 30214078
TI  - Preclinical progression of neurodegenerative diseases.
AB  - Neurodegenerative diseases are disorders that are characterized by a progressive
      decline of the motor and/or cognitive function caused by a selective loss of
      neurons within the central nervous system. Recent advancements in the
      translational research have facilitated extensive insights into the molecular
      pathophysiology of neurodegenerative diseases. Nonetheless, a myriad of compounds
      that suppressed the disease progression in cellular and animal models did not
      exhibit efficacy in clinical trials. Perhaps, various biological, medical, and
      methodological factors could be attributed to unfavorable results of clinical
      trials of such disease-modifying therapies. Primarily, the fact that pathological
      changes at molecular and cellular levels precede the clinical onset by several
      years underscores a pressing need for the initiation of interventions before the
      emergence of neurological symptoms. Using exquisite biomarkers, recent studies
      revealed the preclinical and prodromal progression of pathophysiology, as well as
      compensatory brain responses in several neurodegenerative diseases. This review
      aims to discuss the recent advancement of biomarker studies on presymptomatic
      subjects and the perspective on a preventive trial of disease-modifying therapies
      for devastating neurological disorders.

PMID- 30214080
TI  - Brain research and clinical psychiatry: establishment of a psychiatry brain bank
      in Japan.
AB  - The Japan Agency of Medical Research and Development (AMED) has approved the
      budget for the 5-year project called Establishment of the JAPAN Brain Bank
      Network, which commenced in 2016. This project was established with the aim of
      storing brain tissue samples to enable research on the etiologies and mechanisms
      of psychiatric diseases, which would eventually improve standards of clinical
      treatment for these diseases. Japanese researchers in the field of biological
      psychiatry have historically depended on Western brain banks, particularly from
      Europe and the United States, which is regrettable. To remedy this situation and
      improve the Japanese research standards, attempts for establishing an autonomous
      Japanese brain bank are ongoing. Reviews of the previous attempts on elucidating
      the etiopathology of neuropsychiatric diseases reveal that rapid advances result
      from studies on tissue samples from diseased brains. For example, in the
      Kraepelin era, i.e. in 1900 years before and after, long-term, resolute research
      on diseased brain specimens ultimately led to the discoveries of entities such as
      Alzheimer disease and Lewy body disease. The recent advances in techniques of
      neuroimaging and molecular biology have resulted in a shift of interest from
      brain tissue analysis. However, the integration of findings of all these
      techniques is recommended going forward, with a shift in focus back to brain
      tissue analysis. The JAPAN Brain Bank Network project was launched under this
      setting. The success of this project largely depends on the will of patients and
      family members (for donating samples) as well as cooperation among many
      clinicians. In this paper, we provide a brief overview of the history of
      biological psychiatric research and related perspectives, which will hopefully
      encourage further studies that will help bridge the gap between clinical and
      biological research on psychiatric diseases.

PMID- 30214079
TI  - Congenital diseases caused by defective O-glycosylation of Notch receptors.
AB  - The Notch signaling pathway is highly conserved and essential for animal
      development. It is required for cell differentiation, survival, and
      proliferation. Regulation of Notch signaling is a crucial process for human
      health. Ligands initiate a signal cascade by binding to Notch receptors expressed
      on a neighboring cell. Notch receptors interact with ligands through their
      epidermal growth factor-like repeats (EGF repeats). Most EGF repeats are modified
      by O-glycosylation with residues such as O-linked N-acetylglucosamine (O-GlcNAc),
      O-fucose, and O-glucose. These O-glycan modifications are important for Notch
      function. Defects in O-glycosylation affect Notch-ligand interaction, trafficking
      of Notch receptors, and Notch stability on the cell surface. Although the roles
      of each modification are not fully understood, O-fucose is essential for binding
      of Notch receptors to their ligands. We reported an EGF domain-specific O-GlcNAc
      transferase (EOGT) localized in the endoplasmic reticulum. Mutations in genes
      encoding EOGT or NOTCH1 cause Adams-Oliver syndrome. Dysregulation of Notch
      signaling because of defects or mutations in Notch receptors or Notch signal
      regulating proteins, such as glycosyltransferases, induce a variety of congenital
      disorders. In this review, we discuss O-glycosylation of Notch receptors and
      congenital human diseases caused by defects in O-glycans on Notch receptors.

PMID- 30214082
TI  - Associations of treatment completion against drug addiction with motivational
      interviewing and related factors in Afghanistan.
AB  - Despite the increase in the number of drug treatment centers, patients with drug
      addicts have been increasing without the improvement of treatment in Afghanistan.
      This study aimed to examine the associations of the completion of drug addiction
      treatment with motivational interviewing (MI) and other factors among male drug
      users in Afghanistan. Subjects were patients admitted to Jangalak Hospital in
      Kabul, Afghanistan in 2014 and 2015. Systematic sampling and supplementary
      sampling were applied. The records of 327 males aged 18 to 54 years were
      collected from those of 3,373 male inpatients. Completion of treatment was
      defined as presence and receiving treatment in the hospital for at least 45 days.
      Multiple logistic regression models were applied to estimate the adjusted odds
      ratio (AOR) and 95% confidence interval (CI) for the completion of drug addiction
      treatment. Among the patients, heroin was the most commonly used drug, followed
      by opium, crystal, hashish, and other drugs. Patients with treatment history for
      drug addiction (AOR 2.46; 95% CI 1.14-5.30), those attended MI before admission
      (AOR 43.98; 95% CI 17.21-112.39), and those used heroin (AOR 4.74; 95% CI 1.32
      16.97) were more likely to complete the drug addiction treatment. Among the
      factors examined in this study, attending MI was most strongly associated with
      the completion of drug addiction treatment. Amendments to policies to include
      compulsory MI in standard operational procedures of drug addiction treatment
      before hospitalization may be recommended.

PMID- 30214081
TI  - A review of impaired visual processing and the daily visual world in patients
      with schizophrenia.
AB  - Several studies have investigated perceptual processes in patients with
      schizophrenia. Research confirms that visual impairments are one of the most
      important features of schizophrenia. Many studies, using behavioral and
      psychological experiments, confirm that visual impairments can be used to
      determine illness severity, state, and best treatments. Herein, we review recent
      research pertaining to visual function in patients with schizophrenia and
      highlight the relationship between laboratory findings and subjective, real-life
      reports from patients themselves. The purpose of this review is to 1) describe
      visual impairments that manifest in patients with schizophrenia, 2) examine the
      relationship between visual dysfunction, assessed by laboratory tests, and the
      experiences of patients themselves, and 3) describe real-life experiences related
      to visual function in this population. In this review, the impairments of motion
      and color perception, perceptual organization, and scan paths are summarized,
      along with the relationship between laboratory findings and patients' real-world
      subjective experiences related to visual function.

PMID- 30214083
TI  - Characteristics of falls in orthopedic patients during hospitalization.
AB  - Falls are common in elderly patients and comprise 20-30% of all incident reports
      in hospitals. The current study examined falls in orthopedic patients among
      212,617 inpatients admitted to our hospital from April 2012 to March 2017, using
      a prospective database in the hospital event reporting system. The risk of fall
      was evaluated using a fall assessment scoresheet at admission and during
      hospitalization, based on which patients were divided into risk grades 1, 2 and
      3. Fall leading to fracture or a life-threatening injury was defined as an
      adverse event. The number of falls during the study period was 3,925, including
      230 in orthopedic patients. Fall cases occurred at all times, but adverse events
      were significantly more common from 1-7 a.m. (67% vs. 24%, p<0.01). Patients
      hospitalized for orthopedic surgery had significantly higher fall rates compared
      to all other patients (3.12% vs. 1.80%, p<0.01), and were older (65.8 vs. 61.4
      years, p<0.05) and more frequently >80 years old (23.4% vs. 17.9%, p<0.05). There
      was a significant difference in fall incidence between risk grades 2 and 3 for
      patients hospitalized for non-orthopedic surgery, but not for patients
      hospitalized for orthopedic surgery. We conclude that fall can occur in
      orthopedic patients with a low predicted risk of fall, and particularly for older
      patients. This may indicate that frequent specialized fall assessment is
      desirable after orthopedic surgery.

PMID- 30214084
TI  - <Editors' Choice> Efficacy of enteral nutrients containing beta-hydroxy-beta
      methylbutyrate, glutamine, and arginine for the patients with anastomotic leakage
      after gastrectomy: study protocol of a multicenter phase II clinical trial.
AB  - Anastomotic leakage is a major cause of prolonged hospitalization after
      gastrectomy and sometimes leads to fatal complications, such as abdominal abscess
      and sepsis. Arginine, glutamine, and beta-hydroxy-beta-methylbutyrate (HMB) are
      indispensable for biosynthesis of collagen, which plays an important role in the
      process of wound healing. However, treatment effects of amino acid supplements
      containing HMB on the healing process of anastomotic leakage after gastrectomy
      remain unclear. We designed an open-label, multicenter, phase II clinical trial
      to evaluate the therapeutic efficacy of an enteral amino acid supplement
      consisting of arginine, glutamine, and HMB (Abound, Abbott Japan Co., Ltd.,
      Tokyo, Japan) in patients with anastomotic leakage after gastrectomy. Patients
      who are diagnosed with anastomotic leakage within 14 days after gastrectomy are
      eligible for this trial and the target sample size is 20. A pack of Abound is
      administered twice a day for 2 weeks. The primary objective of this clinical
      trial is to determine the length of time between diagnosis and cure of
      anastomotic leakage. The secondary endpoints include the safety of Abound,
      duration of drainage placement and fasting, postoperative hospital stay, surgical
      procedure, and blood test data. Variables are compared between enrolled patients
      and a historical control consisting of 20 patients who underwent gastrectomy
      between 2004 and 2016 at Nagoya University Hospital. We herein describe the study
      design and the concept in this protocol paper.

PMID- 30214085
TI  - <Editors' Choice> Effect of postoperative doxorubicin administration on ischemic
      wound healing.
AB  - Some patients undergo postoperative chemotherapy despite showing impaired wound
      healing after a major surgery. We speculated that postoperative chemotherapy
      further delays wound healing in these patients. This study aimed to compare the
      effects of doxorubicin (DXR) in ischemic skin flap and normal incisional wound
      models after surgery. A 2-cm incisional wound was made in group 1 rats, and
      saline was injected intravenously, following surgery on the same day. Incisional
      wound was made in group 2-5 rats, and 8 mg/kg DXR was injected intravenously,
      following surgery on the same day and after 7, 14, and 21 days respectively. H
      shaped double flaps were made in group 6 rats, and saline was injected
      intravenously, following surgery on the same day. Flaps were made in group 7-10
      rats, and 8 mg/kg DXR was injected intravenously, following surgery on the same
      day and after 7, 14, and 21 days respectively. On days 7, 14, 21, and 28 after
      surgery, the suture wounds were removed, tensile wound strengths were measured,
      and tissue samples were collected for histopathological evaluation. The tensile
      strength was significantly lower in the DXR-treated groups than in the control
      groups for both ischemic skin flaps and incision wounds. Additionally, the cross
      effect between DXR and ischemia was not significant. On pathological examination,
      DXR showed atrophic skin changes and degeneration of skin appendages on days 14
      21 after the surgery in both the models. DXR decreased the wound tensile strength
      and caused an atrophic change in the ischemic wound.

PMID- 30214086
TI  - Stigma among international students is associated with knowledge of mental
      illness.
AB  - Increasing numbers of international students require Japanese universities to
      provide mental health support as one of their primary responsibilities. The
      problem with the provision of such support is that the stigma of mental disorder
      causes many individuals to avoid seeking help. We aim to clarify the association
      between stigma and mental illness to develop anti-stigma education. We performed
      a cross-sectional observational study. The target population comprised
      international students enrolled in a Japanese university. Online questionnaires
      were used to assess self-stigma, perceived stigma, recognized knowledge of
      schizophrenia and depression, gender, country and region, general mental health
      status, parents' income, non-clinical and clinical help-seeking attitudes, and
      Japanese and English language ability. Logistic regression model was used to
      estimate odds ratios (ORs) for self-stigma and perceived stigma after adjusting
      for the above factors. A total of 119 students were invited to participate, 61
      (51.3%) of whom were enrolled. Students with good knowledge of
      depression/schizophrenia did not indicate more severe self-stigma compared with
      those without such knowledge. Students with good knowledge of schizophrenia
      indicated more severe perceived stigma compared with those without such knowledge
      (OR 3.78 [95% confidence intervals; CI, 1.21-11.78]). Students with good
      knowledge of depression indicated less severe perceived stigma compared with
      those without such knowledge (OR 0.31 [95% CI, 0.10-0.94]). In this study, among
      international students, higher perceived stigma was associated with knowledge of
      schizophrenia and lower knowledge of depression.

PMID- 30214087
TI  - Tobacco Control Law awareness, enforcement, and compliance among high school
      students in Myanmar.
AB  - In Myanmar, the Control of Smoking and Consumption of Tobacco Products Law
      (Tobacco Control Law; TCL), which covers the prohibition of sale of tobacco to
      minors and all forms of tobacco advertisement, was enacted in 2006. This study
      aimed to examine the awareness of the TCL among high school students. A cross
      sectional study was conducted in November 2015. Participants were 1,339 high
      school students (554 boys and 785 girls) from two regions and two states of
      Myanmar. Data were collected using anonymous self-administered questionnaires and
      revealed that 78.0% of boys and 86.5% of girls responded the sale of tobacco
      products in or within 100 feet from school, and 83.4% of boys had ever seen
      someone selling tobacco products to minors. More than half of the students had
      ever seen minors selling or distributing tobacco products, and had knowledge
      about the TCL, while only 9.7% knew about the penalties. The adjusted odds ratio
      (95% confidence interval) of awareness of the TCL was 2.12 (1.35-3.31) for
      students who had ever received tobacco products free of charge, or seen/heard
      about their distribution free of charge, 1.86 (1.20-2.89) for current smokeless
      tobacco users, and 0.58 (0.43-0.77) for students who had ever seen someone
      selling tobacco products to minors. The majority of high school students did not
      know that the violation of the TCL could be punished with a fine and/or
      imprisonment. These findings suggest that awareness of the TCL was very low among
      high school students, highlighting that TCL enforcement and compliance, and
      tobacco-related health education programs are not satisfactory in Myanmar.

PMID- 30214088
TI  - Comparison of twice a day and three times a day meropenem administration in
      elderly patients in a Japanese community hospital.
AB  - Meropenem (MEPM) is a broad-spectrum antibiotic prescribed to patients with
      moderate or severe pneumonia. It is well recognized that appropriate medicine
      reduces the burden on not only young patients but elderly ones as well. We
      enrolled 56 patients aged 75 and over who were diagnosed with moderate or severe
      pneumonia (body temperature: ?37.5  degrees C; white blood cell (WBC) count:
      ?10,000/MUL; C-reactive protein (CRP): ?4 mg/dL) on the basis of Clinical
      Evaluation Methods for New Antimicrobial Agents to Treat Respiratory Infections
      defined by the Japanese Society of Chemotherapy, at the National Hospital
      Organization Kanazawa Medical Center from January 1, 2007 to May 31, 2010. Forty
      two patients were given MEPM twice a day and 14 were given the same drug three
      times a day in a Japanese community hospital. After four days, the three times a
      day group showed significant decreases in body temperature, WBC count, and CRP
      level, which are commonly used indices for evaluating therapeutic effects.
      Similarly, the twice a day group showed decreases of those indices, and both
      treatments had no serious adverse effects. Simulation analysis based on the
      pharmacokinetics-pharmacodynamics (PK/PD) theory revealed that both treatments
      effectively inhibited the activities of Pneumococcus, Haemophilus influenzae,
      Providencia stuartii, and Staphylococcus aureus, which are the major bacteria in
      the patients. In this retrospective study, simulation analysis based on the PK/PD
      theory revealed that even the twice a day MEPM administration has sufficient
      effectiveness against pneumonia. It also may pave the way for the use of
      personalized medicine in the patients.

PMID- 30214089
TI  - Clinical significance of SUVmax on preoperative 18F-fluorodeoxyglucose positron
      emission tomography in patients who underwent R0-esophagectomy for esophageal
      cancer.
AB  - The standardized uptake value (SUV) is a marker of tumor glucose metabolism,
      detected using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and
      may reflect tumor aggressiveness. The purpose of this study was to evaluate the
      clinical significance of maximum SUV (SUVmax) of primary esophageal cancer (EC)
      lesions. A total of 86 patients with EC who underwent pre-treatment FDG-PET and
      R0-resection were included in our study. The mean patient age was 65 years, and
      87% were men. Histologically, cancers included squamous cell carcinomas,
      adenocarcinomas, and other tumors in 72, 3, and 11 patients, respectively.
      Preoperative chemotherapy with or without radiotherapy was performed in 4 and 37
      patients, respectively. Measured patient outcomes included the correlation
      between the SUVmax of the primary EC lesion and clinicopathological factors in
      patients who did not undergo preoperative treatment (n = 45), and the
      investigation of relapse-free survival (RFS) according to SUVmax and the
      relationship between SUVmax and recurrence sites in all patients (n=86). The mean
      SUVmax was 8.9 +/- 4.6, and SUVmax values significantly correlated with tumor
      invasion depth and stage. The 5-year RFS for the enrolled patients was 57%, and
      the RFS of patients with SUVmax < 7.0 was better than that of patients with
      SUVmax >= 7.0, with a marginal difference (p = 0.0892). Lymph node recurrences
      were significantly more common in patients with SUVmax >= 7.0, compared to
      patients with SUVmax < 7.0. Therefore, the SUVmax value of the primary EC lesion
      before preoperative treatment may be predictive of RFS and lymph node recurrence.

PMID- 30214090
TI  - An open-label, single-arm study of CRYO2 for tissue removal at the site of
      central airway obstruction or stenosis: study protocol.
AB  - Argon-plasma coagulation, high-frequency electrosurgical snare, laser therapy,
      and microwave treatment are therapeutic options to reduce tumor-related stenosis
      of the central airway. These treatments may cause airway fire under a high
      concentration of oxygen, so FiO2 levels must be <=40%. This restriction may be
      dangerous when treating patients with respiratory failure. The cryosurgery unit,
      ERBE-CRYO2, facilitates treatment under an FiO2 level of 100%, safely reducing
      this risk. In Japan, CRYO2 has been approved for cryobiopsy and foreign body
      removal, but not for tissue removal at the site of obstruction or stenosis due to
      lack of sufficient evidence. Since CRYO2 may be useful for reducing airway
      stenosis, the present study was designed to increase indications for this unit in
      Japan.

PMID- 30214091
TI  - Characteristics of outpatient falls that occurred in hospital.
AB  - A fall may cause trauma and bone fracture, which can affect ADL and QOL.
      Therefore, countermeasures to prevent falls are important. There are many reports
      on falls in hospitalized patients, but few for outpatients. Therefore, the
      purpose of this study is to report the characteristics of outpatient falls that
      occurred in hospital over five years to identify factors associated with fall in
      these patients. From April 2012 to March 2017, we investigated fall cases in
      outpatients using a hospital database. Fall that led to fracture or a life
      threatening injury was defined as an adverse event. A total of 3,758 patients had
      falls in the hospital, and this included 146 outpatients, giving an incidence of
      3.9% (146/3,758). Most falls involved outpatients in their 70s, and most occurred
      in operating rooms (15%), followed by examination rooms (13%), escalators (10%),
      and waiting rooms (7%). Falls in neurology patients accounted for 12%, followed
      by neurosurgery (10%), and ophthalmology (8%). Among all falls, 5% occurred in
      patients wearing slippers, and 54% and 46% occurred in patients without and with
      a need for assistance with mobility, respectively. There were 6 adverse events
      (4%) due to fall in outpatients: 4 femoral neck fractures, 1 teeth injury, and 1
      pubic bone fracture. In conclusion, a fall accident occurs most commonly in
      outpatients suffering from a neurological disease and in ophthalmologic
      outpatients aged about 70 years old, and is likely to occur in the operating
      room, examination room, escalator and waiting room. Our findings suggest that
      countermeasures for each location are necessary.

PMID- 30214092
TI  - Primary hepatic carcinosarcoma with multimodal treatment.
AB  - Hepatic carcinosarcoma (HCS) generally presents in advanced stages, demonstrates
      aggressive behavior, and has a poor prognosis. Other than curative primary
      resection, no effective treatment options exist. We present a case of resected
      HCS with four repeat resections for solitary lymph node recurrence followed by
      chemoradiotherapy with doxorubicin and ifosfamide. A 67-year-old Japanese man was
      admitted to our hospital for evaluation of an asymptomatic hepatic tumor. The
      patient underwent right hepatectomy with a presumptive preoperative diagnosis of
      atypical hepatocellular carcinoma. Based on histopathological and
      immunohistochemical findings, the tumor was diagnosed as HCS containing
      osteosarcoma and chondrosarcoma components. After the initial surgery, the
      patient underwent four additional resections for solitary lymph node HCS
      recurrence, and then underwent chemoradiotherapy with doxorubicin and ifosfamide
      for an unresectable lymph node recurrence. Chemotherapy was stopped after two
      cycles because of severe adverse events, although chemoradiotherapy markedly
      reduced the size of the lymph node recurrence and provided a progression-free
      survival of 12 months. Thirty-seven months after the initial surgery, the patient
      died of cardiac invasion of multiple mediastinal lymph node metastases. The
      clinical course outlined in this case report suggests that chemoradiotherapy with
      doxorubicin and ifosfamide for metastatic HCS may prolong survival in patients
      with unresectable lesions.

PMID- 30214093
TI  - Meningioma mimicking an intraparenchymal cystic tumor.
AB  - Meningiomas rarely exhibit cystic lesions with mural nodules, and may be
      misdiagnosed as intraparenchymal cystic tumors. We herein present a 64-year-old
      woman with a cystic lesion and enhancing mural nodule in the left temporal lobe
      accompanied by peritumoral brain edema. Differential diagnoses included low-grade
      gliomas, hemangioblastoma, and cystic meningioma. Gross total resection of the
      tumor was achieved through a temporal surgical approach. Intraoperative findings
      showed that the tumor was an extraparenchymal tumor. The cyst was covered by an
      extraparenchymal thin membrane and the cystic fluid was yellowish in color. The
      final result of the pathological examination was microcystic meningioma, WHO
      grade I. Although intraparenchymal tumors, such as hemangioblastoma,
      ganglioglioma, pilocytic astrocytoma, and pleomorphic xanthoastrocytoma, commonly
      display this MRI pattern, meningioma needs to be included in the differential
      diagnosis.

PMID- 30214094
TI  - Response by Lau and Rothwell to Letter Regarding Article, "Antiplatelet treatment
      after transient ischemic attack and ischemic stroke in patients with cerebral
      microbleeds in 2 large cohorts".

PMID- 30214095
TI  - LARGE COVARIANCE ESTIMATION THROUGH ELLIPTICAL FACTOR MODELS.
AB  - We propose a general Principal Orthogonal complEment Thresholding (POET)
      framework for large-scale covariance matrix estimation based on the approximate
      factor model. A set of high level sufficient conditions for the procedure to
      achieve optimal rates of convergence under different matrix norms is established
      to better understand how POET works. Such a framework allows us to recover
      existing results for sub-Gaussian data in a more transparent way that only
      depends on the concentration properties of the sample covariance matrix. As a new
      theoretical contribution, for the first time, such a framework allows us to
      exploit conditional sparsity covariance structure for the heavy-tailed data. In
      particular, for the elliptical distribution, we propose a robust estimator based
      on the marginal and spatial Kendall's tau to satisfy these conditions. In
      addition, we study conditional graphical model under the same framework. The
      technical tools developed in this paper are of general interest to high
      dimensional principal component analysis. Thorough numerical results are also
      provided to back up the developed theory.

PMID- 30214096
TI  - Investigating Variation in Island Effects: A Case Study of Norwegian Wh
      Extraction.
AB  - We present a series of large-scale formal acceptability judgment studies that
      explored Norwegian island phenomena in order to follow up on previous
      observations that speakers of Mainland Scandinavian languages like Norwegian
      accept violations of certain island constraints that are unacceptable in most
      languages cross-linguistically. We tested the acceptability of wh-extraction from
      five island types: whether-, complex NP, subject, adjunct, and relative clause
      (RC) islands. We found clear evidence of subject and adjunct island effects on wh
      extraction. We failed to find evidence that Norwegians accept wh-extraction out
      of complex NPs and RCs. Our participants judged wh-extraction from complex NPs
      and RCs to be just as unacceptable as subject and adjunct island violations. The
      pattern of effects in Norwegian paralleled island effects that recent
      experimental work has documented in other languages like English and Italian
      (Sprouse et al. 2012; Sprouse et al. 2016). Norwegian judgments consistently
      differed from prior findings for one island type: whether-islands. Our results
      reveal that Norwegians exhibit significant inter-individual variation in their
      sensitivity to whether-island effects, with many participants exhibiting no
      sensitivity to whether-island violations whatsoever. We discuss the implications
      of our findings for universalist approaches to island constraints. We also
      suggest ways of reconciling our results with previous observations, and offer a
      systematic experimental framework in which future research can investigate
      factors that govern apparent island insensitivity.

PMID- 30214097
TI  - Prevalence of Hypercholesterolemia, High LDL, and Low HDL in Iran: A Systematic
      Review and Meta-Analysis.
AB  - Background: Chronic and abnormal increase of different types of dyslipidemia
      leads to some important diseases, such as constriction and abstraction of vessels
      in various parts of the body, especially in the heart. High lipid profile, such
      as increased total cholesterol and LDL as well as decreased HDL are recognized as
      cardiovascular disease risk factors. The present study aimed to estimate the
      prevalence of different types of dyslipidemia in Iran by a meta-analysis method.
      Methods: A literature search for studies published during 1998-2015 was carried
      out using both Persian and English databases (SID, Magiran, IranMedex, MedLib,
      PubMed, and Scopus). Keywords such as lipid, dyslipidemia, CVD, cardiovascular
      risk factors, hypercholesterolemia, high LDL-C, low HDL-C, and prevalence were
      used in the search. Random-effects model was used for the analysis using STATA
      (version 11.2). Results: In total, 163 articles were identified of which 49
      articles fulfilled the inclusion criteria. The estimated prevalence (95%
      confidence interval) of eligible articles for high cholesterol >=200 mg/dl and
      >=240 mg/dl was 42% (95% CI: 38-45) and 17% (95% CI: 14-20), respectively.
      Moreover, the prevalence (95% confidence interval) for high LDL-C >=130 mg/dl and
      >=160 mg/dl was 40% (95% CI: 32-48) and 19% (95% CI: 16-23), respectively. The
      pooled prevalence estimate for low HDL-C (<40 among males, <50 among females) was
      43% (95% CI: 33-53) in both sexes of the Iranian people. All types of lipid
      component abnormalities (hypercholesterolemia, high LDL-C, and low HDL-C) were
      more prevalent in women. Conclusion: The results indicate that the prevalence of
      different types of dyslipidemia in Iran is substantial. Given the risk of
      complications (e.g. cardiovascular disease and control of different types of
      dyslipidemia) in Iranian people, it is important to reduce the burden of
      cardiovascular diseases.

PMID- 30214098
TI  - Assessment of Subclinical Myocardial Changes in Non-Alcoholic Fatty Liver
      Disease: A Case-Control Study Using Speckle Tracking Echocardiography.
AB  - Background: Considering the association between cardiac abnormalities and non
      alcoholic fatty liver disease (NAFLD), the present study aimed to evaluate the
      relationship between biopsy-proven NAFLD and functional echocardiographic
      parameters, including left ventricular (LV) global longitudinal strain (GLS) in
      asymptomatic individuals. Methods: Thirty asymptomatic patients with liver biopsy
      proven NAFLD and the same number with no evidence of fatty liver in
      ultrasonography were enrolled in the study as cases and controls, respectively.
      The measured echocardiographic parameters included LV ejection fraction (LVEF),
      LV end-systolic and end-diastolic dimensions (ESD, EDD), LV end-systolic and end
      diastolic volumes (ESV, EDV), E/e' ratio (early-diastolic mitral inflow
      velocity/early-diastolic myocardial velocity), E/A ratio (early-diastolic mitral
      inflow velocity/late-diastolic mitral inflow velocity), and GLS. Data were
      analyzed using the SPSS statistical software (version 18.0) by performing the
      independent t test, Chi-square, and non-parametric Mann-Whitney U tests. P values
      <0.05 were considered statistically significant. Results: A significant
      difference in ESD (32.1+/-1.4 mm vs. 34+/-1.8 mm), EDD (41.9+/-1.7 mm vs. 45.2+/
      3.1 mm), and E/e' ratio (8.4+/-0.8 vs. 7.4+/-1.2) was detected among individuals
      with NAFLD compared with those without NAFLD (P<0.001 for the first two
      parameters and P=0.002 for the last one). GLS was also significantly lower in
      NAFLD patients than in controls, but within normal levels (19.3%+/-2.0 vs.
      21.2%+/-1.4, P<0.001). Conclusion: The findings support the presence of
      subclinical cardiovascular structural and functional changes in patients affected
      by NAFLD. It also indicates that the use of GLS is more sensitive than LVEF for
      the detection of LV systolic dysfunction in NAFLD patients.

PMID- 30214099
TI  - Human Amniotic Membrane Effect on Perianal Fistula Healing in Rabbits: An
      Experimental Study.
AB  - Background: Perianal fistula is a complicated disorder and most difficult to
      manage. New treatment methods would help surgeons to achieve a better outcome in
      patients with perianal fistula. Human amniotic membrane (HAM) has positive
      effects on wound healing in several conditions. The present study aimed to
      further determine the effect of HAM on wound healing of perianal fistula in
      rabbits. Methods: In a prospective experimental study, 14 male rabbits (aged 4-6
      months and weighing 3-4 kg) were randomly divided into 2 groups. After 12 weeks,
      the high type perianal fistula was repaired with endorectal flap (ERF) and ERF
      plus HAM in the control and case groups, respectively. In all rabbits of the case
      group, a 1*1 cm width wrap of HAM was applied and fixed around the ERF site.
      Three weeks later, the repaired site of the perianal fistula was sent for
      pathologic wound healing scoring. The results were analyzed with the SPSS 21.0
      software using Mann-Whitney test. Results: Six rabbits of each group survived the
      study period. There was a statistically significant difference in wound healing
      between the case and control groups (P<0.001). Wound healing process in the case
      group occurred better and faster than the control group. Conclusion: HAM has an
      effective role in enhancing the ERF procedure and considered appropriate. A
      combination of HAM with other methods is recommended.

PMID- 30214100
TI  - Safety Assessment of Mentha mozaffarianii Essential Oil: Acute and Repeated
      Toxicity Studies.
AB  - Background: Mentha mozaffarianii, an endemic species from the Labiatae family, is
      used in Iranian traditional medicine. This study evaluated the acute and repeated
      oral toxicity of the Mentha mozaffarianii essential oil (MMEO) in rats and mice.
      Methods: To assess the toxicity profile of the MMEO, we administered the
      essential oil to 48 rats and mice of both sexes by gavage in acute and repeated
      models. In acute toxicity, the animals were administered the MMEO (2000 mg/kg)
      and were monitored for 14 days. In the repeated toxicity, the MMEO was
      administered (100 mg/kg) daily for 4 weeks. On the 28th day, all the animals were
      scarified and blood and tissue samples were prepared. All the clinical,
      biochemical, and histopathological changes were assessed and compared with those
      in the controls. Statistical significance was determined by one- and two-way
      analyses of variance, followed by the Tukey test using GraphPad Prism 6. Results:
      In the acute test, there was no mortality; therefore, the oral LD50 value
      determined in the mice and rats of both sexes was greater than 2000 mg/kg. In the
      repeated test, the animals received the MMEO and there was no mortality. In the
      biochemical analysis, there were significant increases in blood glucose,
      cholesterol, ALT, AST, ALP, and TSH in the female rats and also in BUN in the
      male rats. The histopathological studies revealed evidence of microscopic lesions
      in the liver, kidney, stomach, and small intestine tissues of the MMEO group.
      Conclusion: The results indicated that the acute toxicity of the MMEO in the mice
      and rats was of a low order and it revealed slight tissue damage to several
      organs when given subchronically at a dose of 100 mg/kg.

PMID- 30214101
TI  - Prevalence of Aminoglycoside Resistance Genes in Enterococcus Strains in
      Kermanshah, Iran.
AB  - Background: This study aimed to investigate the occurrence of aminoglycoside
      resistance and the prevalence of the resistance-modifying enzyme genes, ant(3")
      III, ant(6')-Ia, aac(6')-Ie-aph(2")-Ia, and aph(2')-Id, in Enterococcus strains
      isolated in Kermanshah Province, west of Iran. Methods: In this cross-sectional
      study, 108 enterococcal isolates from urine, wound, blood, and cerebrospinal
      fluid samples were collected. The Enterococcus species were recognized by
      standard phenotypic/biochemical tests. The antimicrobial resistance forms were
      detected using a disc diffusion method. Polymerase chain reaction was designed to
      identify aminoglycoside resistance genes, including ant(3")-III, ant(6')-Ia,
      aac(6')-Ie-aph(2")-Ia, and aph(2')-Id. Results: Totally, 108 strains with a final
      diagnosis of Enterococcus were extracted from 84 (77.8%) urine, 14 (13%) wound, 6
      (5.6%) blood, and 4 (3.7%) cerebrospinal fluid samples. Among the 108
      Enterococcus specimens, 94 (87%) cases were Enterococcus faecalis and 14 (13%)
      were Enterococcus faecium. The highest frequency of resistance was observed for
      erythromycin (88.9%), while the lowest was found for streptomycin (44.4%). The
      frequency of high-level gentamicin resistance was 42.2%. Among the identified
      specimens, 42.6% contained the aac(6')-Ie-aph(2")-I gene, 20.4% contained the
      ant(6')-Ia gene, and 15.7% contained the ant(3")-III gene. A significant
      correlation was found between phenotypic gentamicin resistance and the presence
      of the aminoglycoside resistance genes (P<0.05). Conclusion: This study showed
      the high resistance of Enterococcus strains isolated from hospital samples.
      Compared with the previous studies, the strains isolated in our study showed a
      higher percentage of resistance to aminoglycosides.

PMID- 30214102
TI  - National Minimum Data Set for Antimicrobial Resistance Management: Toward Global
      Surveillance System.
AB  - Background: Success of infection treatment depends on the availability of
      accurate, reliable, and comprehensive data, information, and knowledge at the
      point of therapeutic decision-making. The identification of a national minimum
      data set will support the development and implementation of an effective
      surveillance system. The goal of this study was to develop a national
      antimicrobial resistance surveillance minimum data set. Methods: In this cross
      sectional and descriptive study, data were collected from selected pioneering
      countries and organizations which have national or international antimicrobial
      resistance surveillance systems. A minimum data set checklist was extracted and
      validated. The ultimate data elements of the minimum data set were determined by
      applying the Delphi technique. Results: Through the Delphi technique, we obtained
      80 data elements in 8 axes. The resistance data categories comprised basic,
      clinical, electronic reporting, infection control, microbiology, pharmacy, World
      Health Organization-derived, and expert-recommended data. Relevance coding was
      extracted based on the Iranian electronic health record coding system.
      Conclusion: This study provides a set of data elements and a schematic framework
      for the implementation of an antimicrobial resistance surveillance system. A
      uniform minimum data set was created based on key informants' opinions to cover
      essential needs in the early implementation of a global antimicrobial resistance
      surveillance system in Iran.

PMID- 30214103
TI  - Effects of Two-by-Two Combination Therapy with Valproic Acid, Lithium Chloride,
      and Celecoxib on the Angiogenesis of the Chicken Chorioallantoic Membrane.
AB  - Background: The synergistic effects of valproic acid (VPA), lithium (Li), and
      celecoxib (CX) have been shown in combination therapy against the proliferation
      and metastasis of numerous cancers. Angiogenesis plays a critical role in the
      pathogenesis of tumor growth and metastasis. The aim of the present study was to
      evaluate the antiangiogenic effects of VPA, lithium chloride (LiCl), and CX,
      alone or in 2-by-2 combinations, using the chicken chorioallantoic membrane (CAM)
      assay. Methods: Fertilized chicken eggs were randomly divided into 10 groups:
      control, VPA (1.8 and 3.6 umol/CAM), Li (0.15 and 0.60 umol/CAM), CX (0.02 and
      0.08 umol/CAM), VPA+Li, VPA+CX, and CX+Li (n=10 per group). A window was made on
      the eggshells and the CAMs were exposed to a filter disk containing VPA, LiCl,
      and CX, alone or in 2-by-2 combinations. The control CAMs were treated with
      distilled water (vehicle). Three days after the treatment, the number of vessel
      branch points was counted in each CAM. The data were analyzed using SPSS, version
      15.One-way ANOVA, followed by the Tukey tests, was used to compare the groups. A
      P<0.05 was considered a statistically significant difference between the groups.
      Results: According to the results, all the tested drugs decreased the number of
      the vessel branch points in a dose-dependent manner compared to the control group
      (P<0.001). In addition, combinations of the drugs were more effective in
      decreasing angiogenesis than the use of each drug alone. Conclusion: These
      findings suggest that 2-by-2 combinations of VPA, CX, and LiCl can be considered
      an effective antiangiogenesis therapeutic modality.

PMID- 30214104
TI  - Captopril Attenuates Diazinon-Induced Oxidative Stress: A Subchronic Study in
      Rats.
AB  - Background: Diazinon (DZN) is an organophosphate pesticide commonly used for pest
      control in agriculture. It may engender a variety of negative effects in non
      target species, including humans and animals. The objective of the present study
      was to evaluate the ameliorative properties of captopril (CAP), as a thiol
      containing an angiotensin-converting enzyme inhibitor, against DZN-induced
      oxidative stress. Methods: Twenty-eight male Wistar rats were divided randomly
      into 4 groups. All the rats were treated orally via gavage once a day for 7
      weeks: control (corn oil), CAP (10 mg/kg), DZN (10 mg/kg), and CAP+DZN
      combination (as mentioned above). Oxidative stress indices in blood serum, liver
      and kidney homogenates (malondialdehyde [MDA], total thiol groups, and total
      antioxidant capacity), and erythrocyte hemolysis (superoxide dismutase [SOD] and
      glutathione peroxidase) were evaluated. Statistical analysis was performed using
      GraphPad Prism software, version 6.0 (GraphPad, San Diego, CA, USA), by ANOVA,
      followed by the Tukey post hoc analysis. Results: The MDA content and SOD
      activity increased significantly in the DZN group compared with those in the
      control group. Treatment with CAP in the DZN-exposed group significantly
      decreased (P<0.05) the MDA concentration and the SOD activity. The total thiol
      groups were decreased in the DZN group and elevated again by CAP treatment.
      Conclusion: The co-administration of CAP and DZN was able to attenuate lipid
      peroxidation and enzyme changes caused by DZN.

PMID- 30214105
TI  - 9-cis-Retinoic Acid and 1,25-dihydroxy Vitamin D3 Improve the Differentiation of
      Neural Stem Cells into Oligodendrocytes through the Inhibition of the Notch and
      Wnt Signaling Pathways.
AB  - Background: Differentiating oligodendrocyte precursor cells (OPCs) into
      oligodendrocytes could be improved by inhibiting signaling pathways such as Wnt
      and Notch. 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxyvitamin D3
      (1,25[OH]2D3) can ameliorate oligodendrogenesis. We investigated whether they
      could increase oligodendrogenesis by inhibiting the Wnt and Notch signaling
      pathways. Methods: Cortical neural stem cells were isolated from 14-day-old rat
      embryos and cultured using the neurosphere assay. The cells were treated in 4
      different conditions for 1 week: the negative control group received only the
      basic fibroblast growth factor, the positive control group received only T3
      without growth factors, the RA group was treated with 9-cis-RA, and the Vit D3
      group was treated with 1,25(OH)2D3. The effects of 9-cis-RA and 1,25(OH)2D3 on
      the level of the myelin basic protein (MBP) and the gene expression of the SOX10,
      MBP gene, HES5, and LRP6 were studied using flow cytometry and real-time PCR. The
      data were analyzed using one-way ANOVA with GraphPad Prism. A P value less than
      0.05 was considered significant. Results: The mRNA expressions of the SOX10, MBP,
      and MBP gene were significantly increased in the treated groups compared with the
      negative control group; the increase was similar in the 9-cis-RA group and the
      positive control group. Furthermore, 9-cis-RA significantly decreased the
      expression of the HES5 gene, a Notch signaling pathway transcription factor, and
      1,25(OH)2D3 significantly reduced the expression of the LRP6 gene, a Wnt
      signaling pathway co-receptor. Conclusion: It seems that 9-cis-RA and 1,25(OH)2D3
      are good candidates to improve the differentiation of OPCs into oligodendrocytes.

PMID- 30214106
TI  - An Effective Concentration of 5-Aza-CdR to Induce Cell Death and Apoptosis in
      Human Pancreatic Cancer Cell Line through Reactivating RASSF1A and Up-Regulation
      of Bax Genes.
AB  - Background: Promoter hyper-methylation of tumor suppressor genes is a common
      event that occurs in cancer. As methylation is a reversible modification, agents
      capable of reversing an abnormal methylation status should help to combat cancer.
      5-Aza-CdR is a DNA methyl-transferase inhibitor. The present study aimed to
      evaluate the effect of 5-Aza-CdR on the proliferation of human pancreatic cancer
      cell line (PANC-1) and the expression of RASSF1A and Bax genes. Methods: PANC-1
      cells were cultured and treated with 5 and 10 uM/L of 5-Aza-CdR for 24, 48, 72,
      and 96 hours and the percentages of cell viability and apoptosis were measured by
      MTT and flow cytometry. RASSF1A gene promoter methylation was assessed by methyl
      specific primer-PCR (MSP-PCR) and the expression of RASSF1A and Bax genes was
      measured using quantitative real-time PCR (qPCR). All quantitative data are
      presented as mean+/-SD (standard deviation). The one-way analysis of variance
      (ANOVA) with the LSD post hoc test was performed for statistical analysis using
      the SPSS software package, version 16.0. Results: 3-[4,5-dimethythiaziazol-2yl]
      2,5-diphenyl tetrazoliumbr omide (MTT) assay revealed that 5-Aza-CdR
      significantly inhibit the growth and proliferation of PANC-1. The flow cytometry
      results showed over 40% and 70% of early and late apoptotic cells after treatment
      with 5 and 10 um/L of 5-Aza-CdR, respectively. MSP-PCR data indicated that the
      treatment of cells with 10 um/L 5-Aza-CdR resulted in partial demethylation of
      RASSF1A gene promoter. qPCR results showed significant re-expression of RASSF1A
      and up-regulation of Bax genes after 96 hours treatment of cells with 10 um/L 5
      Aza-CdR versus control cells (P<0.01). Conclusion: The result demonstrated that 5
      and 10 uM of 5-Aza-CdR induce cell death and apoptosis by epigenetic reactivation
      of RASSF1A and up-regulation of Bax genes.

PMID- 30214108
TI  - A Case of Multi-Ulcerative Abscess Due to Brucella abortus in Kerman, South East
      of Iran.
AB  - Cutaneous involvement is an unusual complication in brucellosis that has been
      reported to range between 0.4% and 17%. We here introduce a 40-year-old shepherd,
      who presented with two ulcerative abscesses in his lower left leg. Cultivation of
      the abscess aspirate was positive for Brucella abortus. The first titer of his
      serological test was 1/160, which subsequently rose to 1/640. In countries like
      Iran where brucellosis is still endemic, it is important to take Brucella species
      into account among other pyogenic bacteria as a causative agent of cutaneous
      abscesses.

PMID- 30214107
TI  - Comparing Human Sperm Quality Preserved at Two Different Temperatures; Effect of
      Trolox, Coenzyme Q10 and Extracellular Adenosine Triphosphate.
AB  - Cooling method was proposed to maintain the sperm quality for several days.
      Nevertheless, during this procedure, sperm is encountered to "cold shock", and
      its quality decreases time-dependently. This study was designed to improve the in
      vitro sperm preservation methods. Thirty normal semen samples were examined in
      Shiraz, Iran, 2017. Fifteen samples were incubated at 22-27  degrees C and 15
      samples were cooled moderately to 4  degrees C. Each sample was divided into five
      subgroups; control, solvent, 200 MUM Trolox, 40 MUM Coenzyme Q10, and 10 mM ATP.
      ATP was added only 15 minutes before the analysis. Assessments of motility
      parameters and sperm viability were done every 24 hours. Statistical analysis was
      performed using SPSS 16 software. The differences between two main groups and
      subgroups were compared by t test and one-way ANOVA, respectively. The effect of
      time was analyzed by repeated measurement test. Sperm motility and viability were
      the same in both groups until 24 hours, except the straight line velocity was
      greater in the cold group. Even after 48 hours, progressive motility and sperm
      velocity, but not viability, were still the same. The greatest reduction in
      progressive motility occurred on the second day; and after 72 hours, sperm
      quality was better preserved in 22-27  degrees C. Treatment with Trolox, coenzyme
      Q10, and extracellular ATP did not have effect on sperm quality. Cold temperature
      is recommended for in-vitro sperm preservation up to 24 hours, and 22-27  degrees
      C is preferred for longer time storage. The sperm does not need antioxidant
      therapy for quality maintenance, but the extender media must be supplied with
      nutrients and antibiotics.

PMID- 30214109
TI  - Treatment of the Mirror Foot with Central Ray Resection: Report of 2 Cases.
AB  - The mirror foot is a rare congenital foot anomaly which is often associated with
      6- to 8-toed polydactyly. Postaxial polydactyly is the most common form of this
      anomaly, while central polydactyly is seen infrequently. We report on 2 cases of
      the central mirror-foot anomaly. Calcaneus duplication and fibular hypoplasia
      were present in 1 case. We treated both patients by resecting the middle foot
      rays and narrowing the foot width through cuneiform excision and use of cerclage
      wires or heavy suture approximation of the remaining adjacent rays. In the mirror
      foot, the old and more common treatment was the resection of the border extra
      toes or rays. Central-ray amputation with dorsal and plantar incisions and
      narrowing the foot with soft-tissue reduction and cuneiform excision confer
      excellent functional and cosmetic results.

PMID- 30214110
TI  - First Iranian Experience of the Minimally Invasive Nuss Procedure for Pectus
      Excavatum Repair: A Case Series and Literature Review.
AB  - Pectus excavatum is the most common congenital deformity of the chest wall. The
      most frequently used techniques include Ravitch (costochondral resection) and
      Nuss (minimally invasive pectus repair of pectus excavatum [MIRPE]). The Nuss
      technique includes using temporary metallic bars without costochondral resection
      to correct the chest wall deformity. Modified MIRPE can be learned easily and
      performed safely with few complications. There are no reports of successful MIRPE
      in Iran, although the Ravitch technique is well known. In the present study, we
      report the first Iranian experience with the modified Nuss procedure in 5
      patients with pectus excavatum (age range=13-48 y). All the patients suffered
      from low self-esteem, and one of them complained of low exercise capacity and
      occasional chest pain. With single-lung ventilation and sternal elevation, an
      introducer was entered into the right thoracic cavity and retrosternal tunneling
      was performed under thoracoscopic vision. The introducer was passed to the left
      thoracic cavity and exited on the left thoracic wall. A titanium plate bar was
      implanted and fixed with stabilizers. There were no cases of mortality, and all
      the patients were discharged in good conditions within 2 weeks. Postoperative
      complications consisted of 1 case of pneumothorax and 2 cases of fixed bar
      protrusion. The present case series indicated that a skilled thoracoscopic
      surgeon is able to do the Nuss procedure in Iranian patients with symmetrical
      pectus excavatum with few complications. However, mixed or redo cases require
      more expertise.

PMID- 30214111
TI  - First Report of the Isolation of Nocardia thailandica from the Bronchoalveolar
      Lavage of a Patient in Iran.
AB  - Nocardiae are Gram-positive, filamentous, aerobic, relatively slow-growing, and
      weakly acid-fast bacteria which cause nocardiosis in humans. We describe a 53
      year-old patient with chronic bronchitis referred to Al-Zahra Hospital, Isfahan.
      A bronchial washing sample was taken from the patient. A Nocardia-like
      microorganism was detected in microscopic evaluation. Based on the phenotypic and
      16S rRNA gene sequencing, the isolate was identified as Nocardia thailandica. The
      patient was treated with trimethoprim-sulfamethoxazole and linezolid. This is the
      first report of the isolation of Nocardia thailandica from Iran.

PMID- 30214112
TI  - Experimental Treatment of a Suspected Case of Mycetoma Based on Dot-in-Circle
      Sign.

PMID- 30214113
TI  - Dynamic balance asymmetries in pre-season injury-prevention screening in healthy
      young soccer players using the Modified Star Excursion Balance Test-a pilot
      study.
AB  - [Purpose] The purpose of this preliminary study was to investigate whether young
      players with no history of injury, have developed early asymmetries in dynamic
      balance ability tested via the recommended for screening in sports, Modified Star
      Excursion Balance Test (MSEBT). [Participants and Methods] Twenty-four young
      healthy male soccer players participated in the study having at least 4 years of
      systematic soccer training. The Waterloo Footedness Questionnaire was used to
      discriminate the stability dominant leg (STAB) from the non-stability dominant
      leg (NSTAB). Dynamic balance was assessed via the MSEBT. Participants, after
      familiarization, made 3 attempts in each direction for both legs: a) Anterior
      (AN), b) Posterolateral (PL) and c) Posteromedial (PM). [Results] The sole
      statistically significant performance asymmetry was in the PL direction, in favor
      of the STAB (94.5 +/- 13.3 cm vs. 98.1 +/- 10.4 cm). [Conclusion] The results of
      this pilot study showed a potential for developing dynamic balance asymmetries,
      in soccer players at the age of 13-14 years. Since asymmetry was significant in
      only one direction, further long term monitoring would be helpful to evaluate
      whether this is a growing functional deficit, potentially involving any of the
      other two directions of testing or if it is alleviated with increasing training
      age. These asymmetries could comprise an injury risk factor.

PMID- 30214114
TI  - Effect of radial shock wave on chronic pelvic pain syndrome/chronic prostatitis.
AB  - [Purpose] This study aimed to evaluate the effect of radial extracorporeal shock
      wave therapy (rESWT) on patients with chronic pelvic pain syndrome (CPPS).
      [Participants and Methods] Forty male CPPS patients were randomly assigned into
      either an rESWT group or a control group. The first group was treated with rESWT
      two times per week for four weeks with a protocol 3,000 pulse, 12 Hz at 3 to 5
      bar. The control group was treated with the same protocol, but the device's probe
      had been turned off. The follow-up assessment was done using the National
      Institutes of Health-developed Chronic Prostatitis Symptom Index (NIH-CPSI)
      before treatment, as well as one week, four weeks, and 8 weeks after treatment.
      [Results] No significant difference was found in terms of age, sub-domain, or the
      total score of the NIH-CPSI between the rESWT group and the control group at the
      baseline. A statistically significant decrease was determined in the pain domain,
      urine score, quality of life, and the total NIH-CPSI score of the rESWT group at
      all post-treatment time points. All domains and the total score of the NIH-CPSI
      at all three follow-up time points decreased more significantly in the rESWT
      group as compared to the control group. [Conclusion] The findings of this study
      confirmed that rESWT is an effective method for treating CPPS.

PMID- 30214115
TI  - Effect of hindlimb unloading and reloading on the soleus and plantaris muscles in
      diabetic rats.
AB  - [Purpose] This study aimed to induce disuse muscle atrophy in Goto-Kakizaki rats,
      a type 2 diabetes model, to investigate the effects of reloading on the soleus
      and plantaris muscles. [Materials and Methods] Wistar and Goto-Kakizaki (GK) rats
      were divided into 6 groups: Wistar Control (WC), GK Control (GC), Wistar Tail
      suspension (WS), GK Tail suspension (GS), and Wistar Reload (WR), GK Reload (GR).
      [Results] Investigation of myofiber cross-sectional area in Goto-Kakizaki rat
      soleus muscles indicated that the GS group showed significantly lower values than
      the GC and GR groups. No significant differences were observed between the GC and
      GR groups. However, investigation of plantaris muscles in Goto-Kakizaki rats
      indicated that the GS and GR groups showed a significant decrease compared to the
      GC group. No significant differences were found between the GS and GR groups.
      [Conclusion] Investigation of muscle weight/body weight ratios and myofiber cross
      sectional area in tail suspension groups confirmed the induction of muscular
      atrophy. The differences in the degree of atrophy and recovery in terms of
      myofiber cross-sectional area observed in Goto-Kakizaki rat plantaris muscles may
      be influenced by the myofiber type and diabetes.

PMID- 30214116
TI  - The effect of a short term conservative physiotherapy versus occlusive splinting
      on pain and range of motion in cases of myogenic temporomandibular joint
      dysfunction: a randomized controlled trial.
AB  - [Purpose] This study compared the effects of a short-term conservative
      physiotherapy program versus those of occlusive splinting on pain and range of
      motion in cases of Temporomandibular Joint Dysfunction. [Participants and
      Methods] This study included 112 male and female participants with ages ranging
      from 15-27 years. Outcome measures were pain assessed by the visual analogue
      scale and Temporomandibular Joint Range of Motion measured with the
      Temporomandibular joint opening index. Patients were randomly assigned to one of
      two groups. Conservative physiotherapy was provided to one group 3 days weekly
      while the other group received standard occlusive splinting. Splinting was used
      daily for the total period of treatment. Any adjustments for splints were done by
      the treating dentist. Both groups were treated for a total period of 6 weeks.
      [Results] Between group statistical analysis revealed a significant reduction in
      pain intensity and Temporomandibular joint opening index in favor of the
      conservative physiotherapy group. [Conclusion] Over a treatment period of 6
      consecutive weeks, conservative physiotherapy could be a better initial treatment
      than occlusive splint in relieving pain and improving range of motion in cases of
      myogenic temporomandibular dysfunction.

PMID- 30214117
TI  - Study on the design development of a multi joint ankle foot orthosis.
AB  - [Purpose] The purpose of this study was to investigate the effects of a newly
      designed multi joint ankle-foot orthosis on the gait and dynamic balance of
      stroke patients having foot drop. [Participants and Methods] This study was
      investigated 10 participants who were diagnosed with stroke. Patients were
      evaluated based on a 10-meter walk test, timed up and go test and Berg balance
      scale after each participant wore a plastic ankle-foot orthosis and a multi joint
      ankle-foot orthosis (AFO) that consisted of orthosis joints (having poster-stop
      joint and Klenzak joint functions). [Results] The 10-meter walk test, timed up
      and go test and Berg balance scale showed significant differences in the orthosis
      with the Klenzak joint function. [Conclusion] The appropriate use of Klenzak AFO
      of the newly designed multi joint AFO is expected to have a positive effect on
      improving the gait and balancing ability of stroke patients having foot drop.

PMID- 30214118
TI  - A predictor of aerobic threshold for patients with heart failure with reduced
      ejection fraction.
AB  - [Purpose] The initial cardiopulmonary response to exercise is hypothesized to be
      a useful predictor of aerobic threshold in patients with heart failure. This
      study aimed to evaluate the correlation between aerobic threshold and
      cardiopulmonary responses to exercise onset by comparing patients with heart
      failure using preserved (>=50%) and reduced (<50%) left ventricular ejection
      fractions. [Participants and Methods] Twenty-eight males (age, 36-82 years; 12
      with preserved and 16 with reduced left ventricular ejection fractions) underwent
      a progressive submaximal cardiopulmonary exercise test using a cycle ergometer.
      The aerobic threshold, time constant, and area under the oxygen uptake curve for
      the first 4 min (VO2AUC) were determined. [Results] A significant association was
      observed between aerobic threshold and VO2AUC in the reduced group but not in the
      preserved group. No significant correlations were found between time constant and
      VO2AUC or between aerobic threshold and time constant in either group.
      [Conclusion] The results suggest that VO2AUC measured from exercise onset to an
      initial 4-min period could provide an easily and safely obtained predictor to
      assess aerobic capacity in people with reduced left ventricular ejection
      fractions.

PMID- 30214119
TI  - Novel method for evaluation of frontal plane knee alignment using bony
      prominences in patients with osteoarthritis.
AB  - [Purpose] Angle measurement using images of bony prominences (AMI) determines
      frontal plane knee alignment from the skin surface without using radiation. The
      purpose of this study was to assess the validity and reliability of images
      obtained with the AMI method. [Participants and Methods] The study included 21
      patients with osteoarthritis. We measured the functional axis of the lower limb,
      obtained via full-leg radiography and correlated the findings with the angle of
      dissection and the angle measured with the AMI method. Additionally, we assessed
      the reliability of the AMI method. [Results] The angle obtained using the AMI
      method and the radiographic anatomic axis (the full-leg radiograph)/the
      mechanical axis were well correlated. The AMI method also showed high
      reliability. [Conclusion] The AMI method is a valid and reliable alternative to
      full-leg radiography for imaging of functional and anatomical knee axes. As AMI
      does not use special equipment or involve radiation exposure, the method can be
      used in outside medical facilities and can be repeated over time without
      increased risk to patients.

PMID- 30214120
TI  - Effects of breathing exercises on resting metabolic rate and maximal oxygen
      uptake.
AB  - [Purpose] The aim of the present study is to examine effects of diaphragm
      breathing exercise and feedback breathing exercise on maximal oxygen uptake and
      resting metabolic rate. [Participants and Methods] Thirty-eight healthy
      participants were randomly assigned to two groups; the diaphragm breathing
      exercise group and the feedback breathing exercise group. The diaphragm breathing
      exercise group was asked to perform diaphragm respiration, and the feedback
      breathing exercise group was asked to breathe with feedback breathing device.
      Maximal oxygen uptake and resting metabolic rate were measured before and after
      two breathing exercises. [Results] Significant difference was found in maximal
      oxygen uptake before and after two breathing exercises. There was also
      significant difference in resting metabolic rate before and after diaphragm
      breathing exercise. However, significant difference was not found in resting
      metabolic rate before and after feedback breathing exercise. There were not
      significant between-group differences in both maximal oxygen uptake and resting
      metabolic rate. [Conclusion] Diaphragm breathing exercise and feedback breathing
      exercise could influence maximal oxygen uptake. Diaphragm breathing exercise
      could influence resting metabolic rate, but feedback breathing exercise could
      not.

PMID- 30214121
TI  - Correlation between the Gait Deviation Index and skeletal muscle mass in children
      with spastic cerebral palsy.
AB  - [Purpose] This study aimed to identify a simple and useful muscle parameter for
      use with the Gait Deviation Index in assessment of ambulatory children with
      unilateral and bilateral spastic cerebral palsy. [Participants and Methods]
      Twenty-eight patients (aged 6 to 18 years; 16 females and 12 males) participated
      in this cross-sectional study. Outcome measurements included the Gait Deviation
      Index, grip strength, 5-repetition chair stand test, upper limb skeletal muscle
      mass index, and lower limb skeletal muscle mass index. [Results] By multiple
      regression analysis, significant independent correlations were observed between
      the Gait Deviation Index and 5-repetition chair stand test and the Gait Deviation
      Index and lower limb skeletal muscle mass index, but not between the Gait
      Deviation Index and grip strength or upper limb skeletal muscle mass index.
      [Conclusion] The Gait Deviation Index was correlated with lower limb muscle mass
      in children with spastic cerebral palsy. Determination of lower limb muscle mass
      may be useful gait evaluation.

PMID- 30214122
TI  - Effects of a progressive walking program on the risk of developing locomotive
      syndrome in elderly Japanese people: a single-arm trial.
AB  - [Purpose] This study aimed to identify the efficacy of a progressive walking
      program on the risk of developing locomotive syndrome among untrained elderly
      Japanese people. [Participants and Methods] Twenty-four untrained elderly
      individuals (68 +/- 4 years) completed a 17-week progressive walking program. The
      stand-up, two-step tests and the 25-question geriatric locomotive function scale
      were used to assess the risk of locomotive syndrome at baseline, the 8-week
      midpoint (2 months), and the 17-week endpoint (4 months). Maximal isometric
      muscle strength of the knee extensors and flexors were measured using a
      dynamometer with the hip joint angle at 90 degrees  of flexion and physical
      function (the 30-s sit-to-stand, sit-up, 10-meter walk, and grip strength) were
      evaluated. [Results] The 4-month walking program significantly improved the two
      step test and geriatric locomotive function scale scores. This may be
      attributable to the improvement in knee flexor strength and physical function.
      [Conclusion] A 4-month program of progressive walking effectively lowered the
      risk of developing locomotive syndrome in elderly Japanese people by improving
      knee flexor muscle strength and physical function.

PMID- 30214123
TI  - Effects of 8 weeks of modified hatha yoga training on resting-state brain
      activity and the p300 ERP in patients with physical disability-related stress.
AB  - [Purpose] We examined the effects of Hatha yoga on EEG and ERP in patients with
      physical disability-related stress. [Participants and Methods] Eighteen male and
      female injured workers with high stress levels, aged between 18 to 55 years, were
      evenly divided into two groups: untrained (CG) and trained (TG) modified hatha
      yoga groups. A modified Hatha yoga protocol was designed for this population by
      two certified yoga instructors, approved by a physical therapist, and conducted
      for one hour, three times weekly for 8 weeks. [Results] The results indicated a
      significant increase in alpha EEG activity over the frontal, central, and
      parietal electrodes and the delta EEG activity over the centroparietal electrode
      from pre- to post-training in TG. In addition, significantly faster auditory
      reaction time for target stimuli, as well as lower P300 peak latency of ERP in
      auditory oddball paradigm were obtained in TG after 8 weeks of yoga training
      compare to CG. [Conclusion] Changes in brain activity and ERP components
      following yoga training would support the psychophysiological effects of hatha
      yoga as an adjunct to routine rehabilitation.

PMID- 30214124
TI  - Rehabilitation and early mobilization in the critical patient: systematic review.
AB  - [Purpose] To review the literature that examines rehabilitation and early
      mobilization and that involves different practices (effects of interventions) for
      the critically ill patient. [Materials and Methods] A PRISMA-Systematic review
      has been conducted based on different data sources: Biblioteca Virtual en Salud,
      CINHAL, Pubmed, Scopus, and Web of Science were used to identify randomized
      controlled trials, crossover trials, and case-control studies. [Results] Eleven
      studies were included. Early rehabilitation had no significant effect on the
      length of stay and number of cases of Intensive Care Unit Acquired Weaknesses.
      However, early rehabilitation had a significant effect on the functional status,
      muscle strength, mechanical ventilation duration, walking ability at discharge,
      and health quality of life. [Conclusion] Rehabilitation and early mobilization
      are associated with an increased probability of walking more distance at
      discharge. Early rehabilitation is associated with an increase in functional
      capacity and muscle strength, an improvement in walking distance and better
      perception of the health-related quality of life. Cycloergometer and electrical
      stimulation can be used to maintain muscle strength. Further research is needed
      to establish stronger evidences.

PMID- 30214125
TI  - Correction of pseudoscoliosis (lateral thoracic translation posture) for the
      treatment of low back pain: a CBP(r) case report.
AB  - [Purpose] To present the case of a total reduction of pseudoscoliosis spinal
      deformity in an adult female suffering from recurrent back pains. [Participant
      and Methods] A 29 year old female suffering from recurrent back pains was
      diagnosed with lateral thoracic translation posture; aka pseudoscoliosis. The
      patient was initially given 12 treatments of relief care including spinal
      manipulative therapy, then another 24 treatments receiving the same plus mirror
      image(r) translation traction and exercises. [Results] The patient achieved a
      complete reduction of the lateral thoracic translation posture (pseudoscoliosis)
      as indicated on a post-treatment radiograph after 36 total treatments. Most
      orthopedic tests became normalized and the patients back pains were significantly
      improved after the correction of posture, but only slight improvements after the
      initial 12 sessions of manipulative therapy only. [Conclusion] Pseudoscoliosis is
      structurally reducible by use of CBP(r) mirror image(r) lateral translation
      traction methods and exercises and led to the resolution of back pains in this
      case. The diagnosis of pseudoscoliosis as opposed to true scoliosis is very
      important and likely underdiagnosed in common practice. Upright radiographic
      imaging is essential to differentiate these two spinal disorders and offers no
      harm to the patient. Comprehensive assessment including routine use of x-ray is
      recommended to differentiate between spinal disorders.

PMID- 30214126
TI  - Long-term sustained effect of gait training using a hybrid assistive limb on gait
      stability via prevention of knee collapse in a patient with cerebral palsy: a
      case report.
AB  - [Purpose] The hybrid assistive limb was developed to improve the kinematics and
      muscle activity in patients with neurological and orthopedic conditions. The
      purpose of the present study was to examine the long-term sustained effect of
      gait training using a hybrid assistive limb on gait stability, kinematics, and
      muscle activity by preventing knee collapse in a patient with cerebral palsy.
      [Participant and Methods] A 17 year-old male with cerebral palsy performed gait
      training with a hybrid assistive limb 12 times in 4 weeks. After completion of 12
      sessions of hybrid assistive limb training, monthly follow-up was conducted for 8
      months. The improvement was assessed on the basis of joint angle and muscle
      activity during gait. [Results] The degree of knee collapse observed at baseline
      was improved at 8-month follow-up. Regarding muscle activity, electromyography
      revealed increased activation of the vastus lateralis at 8-month follow-up.
      Moreover, the hip and knee angles were expanded during gait. In particular, the
      knee extension angle at heel contact was increased at 8 months after follow-up.
      [Conclusion] Gait training with a hybrid assistive limb provided improvement of
      gait stability such as kinematics and muscle activity in a patient with cerebral
      palsy. The improved gait stability through prevention of knee collapse achieved
      with hybrid assistive limb training sustained for 8 months.

PMID- 30214127
TI  - Importance of long-term motor function evaluation after prednisolone treatment
      for Duchenne muscular dystrophy.
AB  - [Purpose] Motor function evaluation by physical therapists is considered a
      valuable tool to assess the progression of muscular dystrophies. Few reports have
      described long-term motor function assessment during the administration of
      corticosteroids such as prednisolone (PSL) in these patients. This study examined
      the importance of long-term non-invasive motor function evaluation in a series of
      3 cases. [Participants and Methods] Three boys with Duchenne muscular dystrophy
      who were administered an identical PSL dosage regimen were retrospectively
      evaluated, and motor function tests were compared in them before and after an
      increase in PSL dosage. Regular feedback was obtained from the patients' mothers
      regarding their impressions of their child's motor function after the
      introduction of PSL. [Results] Motor function was conserved or significantly
      improved after an increase in dosage in all cases. Interestingly, subjective
      assessment by mothers revealed a perceived improvement only in case 1 without any
      changes reported in cases 2 or 3. [Conclusion] PSL was demonstrably effective for
      2.5-5 years after initiating PSL treatment, although parental impressions varied.
      Thus, long-term non-invasive evaluation by physical therapists may provide
      important objective data regarding medication efficacy and disease progression.
      Future studies should include long-term testing results as an essential component
      of the discontinuation criteria for PSL.

PMID- 30214128
TI  - Sustainable Land-use Management Under Biodiversity Lag Effects.
AB  - The destruction of natural habitats for agricultural production results in local
      biodiversity loss. Biodiversity loss in turn affects agricultural production
      indirectly through a range of biodiversity-dependent ecosystem services. Land
      conversion thus results in a negative externality, mediated by changes in
      biodiversity. When the consequences of this externality are delayed in time, lack
      of internalization results in overshoot-and-collapse dynamics, which are
      undesirable from a sustainability perspective. Here, we emphasize the importance
      of forward-looking policies for the long-term sustainability of human-nature
      interactions. We show that the internalization of this externality through a land
      tax can result in several win-win effects in the long run. First, more
      biodiversity is preserved at equilibrium, which increases the carrying capacity
      and total well-being of the human population. Second, a taxation path that
      maximizes the discounted sum of human utilities prevents or greatly alleviates
      overshoot-and-collapse crises, thus increasing the sustainability of the system.
      In particular, this result holds in the case of imperfect information regarding
      the precise temporal dynamics of biodiversity loss, suggesting that the design of
      efficient land-use management policies is possible despite incomplete ecological
      data. This study highlights the need to internalize biodiversity-dependent
      externalities through economic incentives, especially under uncertainty regarding
      long-term ecological dynamics.

PMID- 30214129
TI  - A sparse representation and dictionary learning based algorithm for image
      restoration in the presence of Rician noise.
AB  - Rician noise removal for Magnetic Resonance Imaging (MRI) is very important
      because the MRI has been widely used in various clinical applications and the
      associated Rician noise deteriorates the image quality and causes errors in
      interpreting the images. Great efforts have recently been devoted to develop the
      corresponding noise-removal algorithms, particularly the development based on the
      newly-established Total Variation (TV) theorem. However, all the TV-based
      algorithms depend mainly on the gradient information and have been shown to
      produce the so called "blocky" artifact, which also deteriorates the image
      quality and causes image interpretation errors. In order to avoid producing the
      artifact, this paper presents a new de-noising model based on sparse
      representation and dictionary learning. The Split Bregman Iteration strategy is
      employed to implement the model. Furthermore, an appropriate dictionary is
      designed by the use of the Kernel Singular Value Decomposition method, resulting
      in a new Rician noise removal algorithm. Compared with other de-noising
      algorithms, the presented new algorithm can achieve superior performance, in
      terms of quantitative measures of the Structural Similarity Index and Peak Signal
      to Noise Ratio, by a series of experiments using different images in the presence
      of Rician noise.

PMID- 30214130
TI  - Robustness analysis of a green chemistry-based model for the classification of
      silver nanoparticles synthesis processes.
AB  - This paper proposes a robustness analysis based on Multiple Criteria Decision
      Aiding (MCDA). The ensuing model was used to assess the implementation of green
      chemistry principles in the synthesis of silver nanoparticles. Its
      recommendations were also compared to an earlier developed model for the same
      purpose to investigate concordance between the models and potential decision
      support synergies. A three-phase procedure was adopted to achieve the research
      objectives. Firstly, an ordinal ranking of the evaluation criteria used to
      characterize the implementation of green chemistry principles was identified
      through relative ranking analysis. Secondly, a structured selection process for
      an MCDA classification method was conducted, which ensued in the identification
      of Stochastic Multi-Criteria Acceptability Analysis (SMAA). Lastly, the agreement
      of the classifications by the two MCDA models and the resulting synergistic role
      of decision recommendations were studied. This comparison showed that the results
      of the two models agree between 76% and 93% of the simulation set-ups and it
      confirmed that different MCDA models provide a more inclusive and transparent set
      of recommendations. This integrative research confirmed the beneficial
      complementary use of MCDA methods to aid responsible development of
      nanosynthesis, by accounting for multiple objectives and helping communication of
      complex information in a comprehensive and traceable format, suitable for
      stakeholders and/or decision-makers with diverse backgrounds.

PMID- 30214131
TI  - Environmental health aspects of coal ash phytoremediation by selected crops.
AB  - The objective of this research was to determine the effects of growth media
      containing FA and FA mixed with soil on selected crop plants seedlings growth. We
      studied the influence of various FA concentrations (e.g., 0, 10, 20, 30, 40, 50,
      60, 70, 80, 90, and 100% of FA in growth media by weight basis) in FA/soil
      composed media on the germination, growth, and heavy metals uptake of the
      following plants: barley, Sudan grass, ryegrass, rape, alfalfa, and canola.
      Plants were grown on Petri dishes (10 cm diameter, 3 replications) for 14-21
      days, harvested, dried, and weighed. Experiments have been replicated three
      times. The concentrations of Al, B, Ba, Co, Cr, Cu, Mo, Sr, Ti, Tl, and V in
      growth media were determined, and the concentrations of the same elements in
      young plants were analyzed. Addition of 10, 20, and 30% of FA to the soil were
      acceptable for most plants, as compared to FA alone used as a growth media.
      Barley was the only plant of plants used in our research, which was able to
      sustain seedlings growth on media consisting on FA alone. Preliminary results of
      chemical analysis of FA and harvested young plants implicate that plants do not
      accumulate toxic amounts of heavy metals even being grown on media containing
      100% FA. Our research results indicate that coal FA might be used as a plant
      growth media additive. However, additional studies should be undertaken to
      determine the effects of FA on plants grown till maturity.

PMID- 30214132
TI  - Dynamic conflict among heterogeneous groups: a comment on Christensen and
      Radford.

PMID- 30214133
TI  - Organization enhances collective vigilance in the hovering guards of Tetragonisca
      angustula bees.
AB  - One benefit of group living is vigilance against predators. Previous studies have
      investigated the group size effect, where individual vigilance decreases as group
      size increases without reducing the overall ability of the group to detect
      predators. However, there has been comparatively little research on whether the
      positioning of individuals can improve the collective vigilance of the group. We
      studied the coordination of vigilance and its effect on predator detection in the
      eusocial bee Tetragonisca angustula. Nests are defended by hovering guards that
      detect and intercept intruders before they reach the nest entrance, in addition
      to those that stand upon it. We show that hovering guards are positioned
      nonrandomly, with a strong tendency for equal numbers on both sides of the
      entrance. This organization increases the collective vigilance of the guard
      group, as groups distributed in an even ratio, either side of the entrance, have
      a greater collective field of view than groups that deviate from an even ratio.
      Finally, we use a bioassay to show that when guards are on both sides of the
      entrance, their ability to detect intruders before they reach the entrance
      increases. Overall, our results provide strong evidence that vigilance is
      coordinated and that this improves nest defense. Although other group-living
      animals are often selfish in their individual vigilance behaviors and face
      competing time constraints such as foraging, the altruistic nature of eusocial
      insect workers has probably facilitated the evolution of coordinated vigilance,
      as documented here in T. angustula.

PMID- 30214135
TI  - Experimental cross-fostering of eggs reveals effects of territory quality on
      reproductive allocation.
AB  - Parental and territory quality are often correlated in territorial birds, and
      both factors influence the resources allocated to offspring. Surprisingly, the
      relative contribution of these two components of variation in parental investment
      remains obscure. We experimentally decoupled the normal covariation between
      parental quality and territory quality to test the hypothesis that territory
      quality influences female prenatal and postnatal reproductive allocation.
      Territories were categorized into low-, intermediate-, and high-quality based on
      fledging success of nests over the previous 6 years (nesting sites are fixed in
      space).To decouple covariation between territory quality and individual quality,
      nestbox entrance size was increased on high-quality territories and left small on
      poor-quality sites because house wrens (Troglodytes aedon) prefer small over
      large entrances to their nest sites. We found a significant prenatal effect of
      territory quality on nestling provisioning: when reared on intermediate-quality
      territories, nestlings hatching from eggs produced on low-quality territories
      were provisioned at a higher rate than those hatching from eggs produced on high
      quality territories. We propose that the increased provisioning was brought about
      by increased nestling begging mediated by a maternally derived compound, such as
      corticosterone, transferred to the eggs of stressed females in poor-quality
      habitat.

PMID- 30214136
TI  - Recruiting Students into Science: Evaluating the Impact of the North Dakota IDeA
      Network of Biomedical Research Excellence.

PMID- 30214134
TI  - Genomic analysis of MHC-based mate choice in the monogamous California mouse.
AB  - Variation at Major Histocompatibility Complex (MHC) genes is thought to be an
      important mechanism underlying mate choice in vertebrates, with individuals
      typically predicted to prefer MHC-dissimilar reproductive partners. However,
      analyses based on individual MHC loci have generated contradictory results
      regarding the role of these genes in mate-choice decisions. To provide a more
      comprehensive assessment of relationships between MHC variation and mating
      behavior, we used an exome capture strategy to characterize variability at 13 MHC
      loci, 312 innate immune system genes, and 1044 nonimmune genes in 25 obligate
      monogamous pairs of California mice (Peromyscus californicus) from 2 free-living
      populations of this species in Monterey County, California. Pairwise genotypic
      comparisons and analyses of SNP-based allelic differences failed to detect
      disassortative mating based on MHC variability; reproductive partners were not
      more dissimilar than randomly generated male-female pairs at MHC, innate or
      nonimmune loci. Within populations, individuals tended to be more closely related
      at MHC genes than at innate or nonimmune genes. Consistent with the functional
      role of immunogenes, the 2 study populations were highly differentiated at MHC
      and innate genes but not at nonimmune loci. Collectively, our results suggest
      that MHC genetic variation in California mice reflects local differences in
      pathogen exposure rather than disassortative mating based on variability at MHC
      Class I and II genes.

PMID- 30214137
TI  - The Relation Between the Two Factors of Psychopathy and Intimate Partner
      Aggression.
AB  - Psychopathy is a personality disorder that has emerged as a correlate of
      antisocial, impulsive, and violent behavior, including intimate partner violence
      (IPV). In the current study, we sought to explore the complex relationship
      between two factors of psychopathy and IPV perpetration. The Fearlessness
      Dominance Factor 1 (PPI-I) assesses the affective-interpersonal traits of
      psychopathy, whereas the Impulsive-Antisociality Factor II (PPI-II) assesses the
      behavioral-lifestyle traits of psychopathy. Data from 114 couples was utilized in
      the current study. When using male self-report of IPV, all forms of violence were
      significantly correlated with PPI-I. No male self-report or female-report of any
      of the forms of violence were significantly correlated with PPI-II. Hierarchical
      regression was utilized to study the impact of psychopathy factors in predicting
      physical violence while controlling for demographic variables. In predicting
      women's report of men's violence, the addition of psychopathy factors to the
      model explained significantly more of the variance (F = 2.71; p < .05) above and
      beyond demographic variables. The addition of psychopathy factors to the model
      predicting men's self-reported physical violence was also significant (F = 4.78,
      p < .001). These results suggest that individuals high in PPI-I may be at higher
      risk of IPV perpetration compared to those high in PPI-II.

PMID- 30214138
TI  - Impact of the anterior-posterior corneal radius ratio on intraocular lens power
      calculation errors.
AB  - Purpose: To evaluate the distribution of the anterior-posterior corneal radius
      ratio (AP ratio; anterior corneal radius/posterior corneal radius) in patients
      before cataract surgery, and investigate which parameters can affect this ratio.
      We also investigated the impact of the AP ratio on the intraocular lens (IOL)
      power calculation error in cataract surgery. Method: A total of 501 eyes of 501
      consecutive patients who had no history of corneal diseases and had undergone
      cataract surgery were enrolled in this study. The patients' AP ratio was measured
      before surgery using anterior segment optical coherence tomography; using these
      data, we evaluated the correlation between the AP ratio and various parameters
      that can affect the corneal radius. For subgroup analyses, we investigated the
      correlation between the AP ratio and IOL power calculation error in 181 eyes of
      181 patients. Stepwise multiple regression analysis was performed with the IOL
      power calculation errors of the SRK/T, Haigis, Holladay 1, and Hoffer Q formulas
      as the dependent variables and various parameters that can affect the
      postoperative IOL power calculation error as the independent variables. Results:
      The mean AP ratio was 1.19+/-0.02, and it weakly correlated with corneal
      thickness, horizontal corneal diameter, and posterior corneal radius. The
      correlations between the AP ratio and IOL power calculation errors in the 4
      calculation formulas were not statistically significant. Stepwise multiple
      regression analysis could not detect any significant parameters affecting this
      ratio. Conclusion: The AP ratio has no major influence on IOL power calculation
      error in patients with any history of corneal disease.

PMID- 30214139
TI  - The use of WaveLight Contoura to create a uniform cornea: 6-month results with
      subjective patient surveys.
AB  - Purpose: The aim of this study was to report on the 6-month visual results of
      Contoura with Layer Yolked Reduction of Astigmatism (LYRA) protocol, as well as
      the subjective patient-reported outcomes (PRO) by standardized survey. Patients
      and methods: A retrospective analysis was conducted in 50 consecutive eyes with 6
      month results that had bilateral Contoura laser-assisted in situ keratomileusis
      (LASIK) correction of measured astigmatism and axis using the LYRA protocol. PRO
      were measured via the Refractive Status and Vision Profile (RSVP) standardized
      survey. Objective visual results, subjective patient results, and rates of
      regression were reported. Results: Most (78%) of the eyes achieved an uncorrected
      visual acuity (UCVA) of 20/15 and 98% of the eyes achieved an UCVA of 20/20
      vision after primary correction. After enhancements, the percentage of
      uncorrected eyes achieving 20/15 vision was 90 and 20/20 vision was 100. RSVP
      patient-related outcomes showed that all patients (100%) were either satisfied or
      very satisfied with their vision. Most patients (21/25, 84%) were very satisfied.
      On a numerical ordinal scale of 1-10 (where 10 is the best vision), as reported
      by patients post-operative (post-op), 15 (60%) patients reported a vision score
      of 10, nine (36%) patients reported a score of 9, and one (4%) patient reported a
      score of 8. Initial correction was accurate on all patients, but nine eyes had
      refractive error changes due to epithelial masking of higher order aberrations
      (HOAs) over the follow-up period, a number that was also likely artificially high
      due to study bias. Conclusion: Contoura measured axis and astigmatism-eliminated
      HOA, resulting in a more uniform cornea with an accurate removal of astigmatism,
      excellent 20/15 and 20/20 visual outcomes, and favorable patient-reported
      subjective outcomes.

PMID- 30214140
TI  - Intracameral cefuroxime in combined pars plana vitrectomy and
      phacoemulsification: a study of safety.
AB  - Background: Postoperative endophthalmitis is a severe complication after
      intraocular surgery. The aim of this pilot study was to investigate the safety of
      intracameral cefuroxime in combined vitrectomy and phacoemulsification for
      cataract and various vitreoretinal disease. Methods: The charts of 152 patients
      who underwent combined phacoemulsification, intraocular lens implant and pars
      plana vitrectomy were reviewed. The final tamponade was chosen among fluid, air,
      gas or silicone oil, based on the requirement of each single case. Patients were
      operated on by four different surgeons. At the end of surgery, 1 mg/0.1 mL of
      intracameral cefuroxime (Aprokam) was administered. Results: The mean follow-up
      was 6.26+/-7.78 months (range 1-12). No retinal complication, such as retinal
      infarction or hemorrhages were observed. No acute macular serous detachment and
      no new intraretinal cysts were noted, in those patients who received optical
      coherence tomography within the fifth day after surgery. No endophthalmitis was
      recorded. Conclusion: Intracameral cefuroxime, at the end of combined
      phacoemulsification and pars plana vitrectomy, is safe as it has no toxicity on
      the retina and maybe could be considered effective in endophthalmitis prevention.
      Due to the relatively small number of patients, further studies are advisable.
      Summary statement: The standard dose of intracameral cefuroxime at the end of
      combined phacoemulsification and pars plana vitrectomy has no toxic effects on
      the retina. This paper/The abstract of this paper was presented at the European
      Vitreo Retinal Society Conference 2017 as a conference talk with interim
      findings. The poster's abstract was not published.

PMID- 30214141
TI  - Development of a highly sensitive and reliable enzyme-linked immunosorbent assay
      for MUC5AC in human tears extracted from Schirmer strips.
AB  - Purpose: Reliable measurement of MUC5AC in human tears is essential for
      elucidation of the pathophysiological role of MUC5AC in dry eye disease. The
      purpose of this study was to develop a sensitive and reliable method for
      measurement of MUC5AC in human tear samples extracted from Schirmer strips by
      modifying a commercially available ELISA. Methods: MUC5AC was extracted from
      Schirmer strips containing human tears by PBS with various concentrations of
      polysorbate 20. The extracts were treated with neuraminidase A to cleave the
      sialic acids in MUC5AC. An ELISA plate was blocked to prevent nonspecific
      binding. The rate of extraction of MUC5AC from Schirmer strips, linearity of
      dilution, limit of quantification, calibration range, and intra-assay and inter
      assay reproducibility were examined. Results: MUC5AC was extracted using
      polysorbate 20 in a concentration-dependent manner. Extraction was more efficient
      at 37 degrees C than at 25 degrees C. The signal-to-noise ratio of the assay was
      dramatically increased by treatment with neuraminidase A. Treatment with a
      blocking reagent before incubation produced good linearity of dilution. The inter
      assay and intra-assay coefficients of variation were <=16.6%. The relative error
      was within 13%. Conclusion: We developed an efficient method for extraction of
      MUC5AC from Schirmer strips and a highly sensitive, reliable assay for MUC5AC in
      human tear samples using a commercially available ELISA kit. This method will aid
      in our understanding of the pathophysiology of dry eye, assessment of the effects
      of treatment in daily practice, and selection of appropriate therapeutic agents
      for patients.

PMID- 30214142
TI  - Myopia prevalence and risk factors in children.
AB  - Purpose: To evaluate the prevalence and risk factors for pediatric myopia in a
      contemporary American cohort. Methods: A cross-sectional study of pediatric
      patients enrolled in the Kaiser Permanente Southern California health plan was
      done. Eligible patients were 5- to 19-years old between January 1, 2008, through
      December 31, 2013, and received an ophthalmologic or optometric refraction.
      Electronic medical records were reviewed for demographic data, refraction
      results, and exercise data. Prevalence and relative risks of myopia (defined as
      <=-1.0 diopter) were characterized. Age, sex, race/ethnicity, median neighborhood
      income, and minutes of exercise per day were examined as risk factors. Results:
      There were 60,789 patients who met the inclusion criteria, of which 41.9% had
      myopia. Myopia was more common in older children (14.8% in 5- to 7-year olds,
      59.0% in 17- to 19-year olds). Asian/Pacific Islander patients (OR 1.64, CI 1.58
      1.70) had an increased rate of myopia compared to White patients as did African
      Americans to a lesser extent (OR 1.08, CI 1.03-1.13). Median neighborhood
      household income of $25,000-40,000 was associated with lower rates of myopia (OR
      0.90, CI 0.83-0.97) compared to median neighborhood household incomes less than
      $25,000. Having at least 60 min of daily exercise was associated with lower
      prevalence of myopia (OR 0.87, CI 0.85-0.89). Discussion: Myopia was common in
      this large and diverse Southern Californian pediatric cohort. The prevalence of
      myopia increases with age. Asian children are at highest risk for myopia.
      Exercise is associated with a lower rate of myopia and represents an important
      potentially modifiable risk factor that may be a target for future public health
      efforts.

PMID- 30214144
TI  - Selective laser trabeculoplasty vs micropulse laser trabeculoplasty in open-angle
      glaucoma.
AB  - Aim: The aim of this study was to prospectively compare the efficacy, safety, and
      tolerability of selective laser trabeculoplasty (SLT) vs micropulse laser
      trabeculoplasty (MLT) in reducing intraocular pressure (IOP) in open-angle
      glaucoma patients. Patients and methods: In all, 38 patients were randomized to
      360 degrees  MLT and 31 patients were randomized to 360 degrees  SLT. IOP was
      measured at intervals of 1 hour and 1, 1-6, 6-12, 6-24, 24-36, and 36-52 weeks.
      Patients completed a survey 1 week after the procedure. Patients with end-stage,
      neovascular, uveitic, or angle-closure glaucoma were excluded. Treatment response
      was defined as an IOP reduction of >=20.0% or >=3 mmHg from baseline. Results:
      IOP was lowered to >=3 mmHg from baseline among 37.0% of the micropulse patients
      and 36.0% of patients in the selective laser group at 24-52 weeks. Similarly,
      29.6% of the micropulse patients and 36.0% of the selective laser patients
      experienced a 20.0% IOP decrease from baseline during the 24-52-week interval
      (P=0.77). Both groups revealed similar reductions in IOP as absolute values and
      percentage decreases from baseline at all intervals up to 52 weeks post
      treatment. There were more treatment failures in the micropulse group up to 52
      weeks post laser treatment; however, this was not statistically significant. The
      micropulse group reported less pain both during and after the procedure
      (P=0.005). Conclusion: Micropulse trabeculoplasty has demonstrated similar
      efficacy to SLT over a 52-week follow-up period with less discomfort experienced
      both during and after the procedure.

PMID- 30214143
TI  - Two-year outcome of treat-and-extend aflibercept after ranibizumab in age-related
      macular degeneration and polypoidal choroidal vasculopathy patients.
AB  - Background: The purpose of the study was to evaluate the 2-year outcome and
      predictive factors of treat-and-extend aflibercept in patients with eyes affected
      by typical neovascular age-related macula degenelation (t-AMD) or polypoidal
      choroidal vasculopathy (PCV), who were switched from ranibizumab. Patients and
      methods: The patients underwent three monthly aflibercept injections and
      subsequent administration following the treat-and-extend protocol. Sixty-two eyes
      of 62 patients were reviewed retrospectively. R statistical software was used for
      statistical analysis. Results: Twenty-two eyes were t-AMD and the remaining 40
      eyes were PCV. There was no significant difference in the logarithm of the
      minimal angle of resolution visual acuity (VA) between baseline and 2 years after
      switching to aflibercept (0.40 vs 0.40; P=0.99). Multivariate analyses suggested
      that the following factors were significantly correlated with better VA at 2
      years after switching to aflibercept: patients with PCV, the absence of
      intraretinal fluid at baseline, and better VA at baseline. Conclusion: In
      conclusion, VA was maintained and there was an anatomical improvement at 2 years
      in patients with t-AMD and PCV who were switched from ranibizumab to treat-and
      extend aflibercept. PCV patients showed more favorable visual outcomes and less
      injections at 2 years compared to t-AMD patients. Intraretinal fluid and VA at
      baseline were predictors of VA at 2 years.

PMID- 30214145
TI  - Scleral buckling in the management of rhegmatogenous retinal detachment: patient
      selection and perspectives.
AB  - Although the technique of pars plana vitrectomy (PPV) develops rapidly, scleral
      buckling (SB) has several advantages over PPV for rhegmatogenous retinal
      detachment (RRD), including early visual rehabilitation and prevention of
      cataract progression. It is recommended to select the primary procedure for RRD
      by considering the advantages and disadvantages of each procedure based on the
      patient status. The vitreous body status affects the features of RRD. Vitreous
      liquefaction is an age-dependent process, resulting in the development of
      posterior vitreous detachment (PVD). RRD is usually associated with PVD,
      typically presenting with a retinal tear, strong vitreoretinal traction, and
      bullous detachment. In contrast, RRD may develop without PVD, and typically
      presents with a small atrophic hole, shallow detachment, and slow progression.
      RRD with less liquefied vitreous and no PVD can be managed successfully with SB
      alone even in the presence of subretinal strand as less liquefied vitreous acts
      as bio-tamponade blocking fluid passage. The strong traction induced by PVD and
      bullous detachment in an eye with extensively liquefied vitreous reduces the
      success rate of SB. PPV is gaining popularity as the primary procedure for RRD,
      especially in eyes with retinal tears, PVD, or pseudophakia. Nevertheless, SB
      remains the preferred procedure in young phakic patients without PVD.

PMID- 30214146
TI  - Effect of quantitative intraocular pressure reduction on visual field defect
      progression in normal tension glaucoma under medical therapy applying Markov
      model.
AB  - Purpose: To quantitatively evaluate the association of intraocular pressure (IOP)
      reduction with visual field defect (VFD) progression in normal tension glaucoma
      (NTG) under medical therapy. Patients and methods: Clinical data for 622 eyes of
      311 primary open-angle glaucoma and NTG patients were collected from April 2006
      to March 2016. Of these patients, those with normal IOP, glaucomatous VFD by
      Anderson's criteria, corrected visual acuity >=0.7, >5 years of medical therapy,
      >=5 visual field tests at least five times at 12-month intervals, visual field
      testing reliability coefficients of <=33%, and mean deviation (MD) exceeding
      below -20 dB in the initial visual field test were included in this retrospective
      data analysis. MD and IOP data were collected at baseline and after 5 years.
      Following MD categorization into stages I to IV, stage transition matrices were
      generated using a Markov model to evaluate VFD changes. Eyes were divided based
      on IOP reduction (0%, 10%, 15%, 20%, 25%, 30%) from baseline. VFD aggravations
      were compared using the Markov model and MD slopes with IOP reduction rates as
      cutoff values. Results: Overall, 132 eyes of 132 NTG patients fulfilled the
      eligibility criteria. MD decreased significantly (P<0.0001) at 5 years vs
      baseline. During follow-up, visual field stage using the Markov model was
      constant in ~60%, with transitions in ~40%. IOP decreased significantly (P>0.001)
      at 5 years vs baseline. Though MD slopes did not differ significantly between
      each of the groups that achieved the various IOP reduction cut-off values and the
      corresponding group that did not achieve the cut-off values, a significant
      difference (P=0.0432) in VFD was found between the group that achieved the 25%
      cut-off value and the group that did not when evaluated using the Markov model.
      Conclusion: In NTG patients, VFD aggravation was significantly suppressed in
      groups with IOP reductions of >=25% from baseline.

PMID- 30214147
TI  - Endophthalmitis rates among patients receiving intravitreal anti-VEGF injections:
      a USA claims analysis.
AB  - Purpose: Intravitreal (IVT) injections of the anti-vascular endothelial growth
      factor (VEGF) agents aflibercept, bevacizumab, and ranibizumab are commonly
      prescribed to treat neovascular age-related macular degeneration (nAMD). Studies
      comparing inflammation rates in large populations of patients receiving these
      agents and the treatment of ocular inflammation post-IVT anti-VEGF injections are
      scarce. In this study, we compared rates of endophthalmitis claims (sterile and
      infectious) following IVT anti-VEGF injections to determine the risk factors
      associated with developing endophthalmitis, and examined the claims for
      subsequent treatment. Patients and methods: This retrospective cohort study of
      USA claims data examined the risk of developing endophthalmitis following IVT
      injection of aflibercept, bevacizumab, or ranibizumab in patients with nAMD
      between 11/18/2011 and 5/31/2013. The primary study outcome was occurrence of
      endophthalmitis within 30 days of a claim for an IVT anti-VEGF injection.
      Endophthalmitis rates were calculated separately for aflibercept, bevacizumab,
      and ranibizumab, followed by pairwise comparisons of endophthalmitis frequencies
      among the 3 treatments. Results: This analysis included 818,558 injections from
      156,594 patients with nAMD. The rates (% [n/N]) of endophthalmitis following
      aflibercept, bevacizumab, and ranibizumab IVT injections were 0.100%
      (136/135,973), 0.056% (268/481,572), and 0.047% (94/201,013), respectively. In a
      multivariate analysis, aflibercept was associated with a significantly higher
      risk of endophthalmitis vs ranibizumab (adjusted odds ratio, 2.19; 95% CI: 1.68
      2.85; P<0.0001). The risk of endophthalmitis was similar for bevacizumab and
      ranibizumab. Within 14 days after endophthalmitis, 38.6% of cases received
      injectable antibiotics, 15.3% received injectable steroids, and 30.3% underwent
      vitrectomy. Conclusion: The rate of endophthalmitis was very low, but higher
      following IVT injection with aflibercept compared with both bevacizumab and
      ranibizumab in patients with nAMD.

PMID- 30214148
TI  - Ocular findings in Japanese children with Down syndrome: the course of visual
      acuity and refraction, and systemic and ocular anomalies.
AB  - Purpose: To investigate the age-related development of refractive errors and
      changes of visual acuity (VA), and the systemic and ocular anomalies in Japanese
      children and young adults with Down syndrome (DS). Design: Retrospective cohort
      study. Subjects and methods: This study involved 222 Japanese children and young
      adults with DS (age range: 3 months to 19 years) seen at the Department of
      Ophthalmology, Shiga Medical Center for Children, Shiga, Japan. The subjects were
      divided into the following six age groups: 1) infant (age 0 to <4 years), 2)
      preschool (age 4 to <7 years), 3) lower primary-school grades (age 7 to <10
      years), 4) upper primary-school grades (age 10 to <13 years), 5) junior high
      school (age 13 to <16 years), and 6) late teen/young adults (age 16 to <20
      years). Through examination of the subjects' medical charts, we investigated the
      development and changes of refractive errors and VA, best-corrected VA (BCVA),
      and systemic and ocular anomalies. Results: For vision testing, Teller Acuity
      CardsTM (Bernell Corporation) were used for the infants, and the Landolt ring was
      used for the school-age children. VA was found to develop with age. Mean BCVA was
      0.19+/-0.17 logarithm of the minimum angle of resolution (mean age: 11.3+/-3.2
      years). Mean of refractive errors was hyperopia in the infant (2.2+/-2.4 diopters
      [D] OD, 2.4+/-2.5D OS), yet became myopia to the junior high school (-0.3+/-4.4D
      OD, -0.2+/-4.4D OS). Conclusion: Our findings revealed that in children and in
      late-teen and young-adult subjects with DS, VA slowly develops and that
      refractive errors requiring correction exist and are difficult to examine.

PMID- 30214149
TI  - Focus on biosimilar etanercept - bioequivalence and interchangeability.
AB  - Background: The recent approval of reference etanercept (re-ETN) biosimilars SB4,
      GP2015, and HD203 produced relevant changes in the management of rheumatoid
      arthritis (RA), psoriatic arthritis, and ankylosing spondylitis due to the
      considerably lower cost of these products and the consequent savings. Aims: To
      review the pharmacodynamics, pharmacokinetics, efficacy, and safety of ETN
      biosimilars when employed as first-line therapy or after transition from re-ETN.
      Patients' acceptability was also addressed. Evidence review: The available
      literature was reviewed through a search of PubMed database, and abstract books
      of the American College for Rheumatology and European League Against Rheumatism
      annual meetings. SB4, GP2015, and HD203 were licensed by the US, European and
      South Korea regulatory agencies after the bioequivalence to re-ETN was
      demonstrated through pharmacodynamic and pharmacokinetic studies, and randomized,
      head to head, controlled trials. Based on the evidence of efficacy and safety of
      SB4 and HD203 in RA, and of GP2015 in psoriasis, by the extrapolation principle,
      the three biosimilars were approved for all indications licensed for re-ETN, and
      the regulatory agencies introduced the interchangeability from the originator to
      the biosimilar. Extrapolation of indications, and particularly interchangeability
      raised relevant concerns among the rheumatologists due to the low level of
      evidence supporting the switching strategy (or transition). Rheumatologists'
      concerns are oriented toward the relevant number of biosimilar discontinuations
      after the transition ranging from 7%-17% over a short-term follow-up period. As
      resulted from two studies, at least 20%-30% of the patients claimed more
      exhaustive information on the switching procedure. Conclusion: Based on the
      available evidence, re-ETN biosimilars may be a good option as first-line
      therapy, while further data are needed to definitively establish the efficacy,
      safety, and the economic reflexes of transitioning from re-ETN.

PMID- 30214150
TI  - Fabrication and characterization of dexibuprofen nanocrystals using microchannel
      fluidic rector.
AB  - Purpose: Dexibuprofen is an enantiomer of ibuprofen with low bioavailability
      which results from its hydrophobic nature. Nanosuspensions have developed a
      podium to solve the in vitro dissolution problem that frequently occurs in
      current research. Materials and methods: The drug and polymer solutions were
      mixed in a microchannel fluid reactor and the successive embryonic nanosuspension
      was decanted into a vial having the polymer solution. The impact of different
      process and formulation parameters including inlet angle, antisolvent and solvent
      flow rate(s), mixing time, drug concentration, polymer type and concentration was
      evaluated. Results and discussion: Stable dexibuprofen nanocrystals with a
      particle size of 45+/-3.0 nm and polydispersity index of 0.19+/-0.06 were
      obtained. Differential scanning calorimetry and powder X-ray diffraction
      confirmed the crystallinity. The key parameters observed were inlet angle 10
      degrees , antisolvent to solvent volume of 2.0/0.5 mL/min, 60 minutes mixing with
      5 minutes sonication, Poloxamer-407 with a concentration of 0.5% w/v and drug
      concentration (5 mg/mm). The 60-day stability studies revealed that the
      nanocrystals were stable at 4 degrees C and 25 degrees C. The scanning electron
      microscopy and transmission electron microscopy images showed crystalline
      morphology with a homogeneous distribution. Conclusion: Stable dexibuprofen
      nanocrystals with retentive distinctive characteristics and having marked
      dissolution rate compared to raw and marketed formulations were efficiently
      fabricated. In future perspectives, these nanocrystals could be converted to
      solid dosage form and the process can be industrialized by chemical engineering
      approach.

PMID- 30214151
TI  - Spectroscopic and molecular modeling studies of binding interaction between
      bovine serum albumin and roflumilast.
AB  - Background: The binding interaction between bovine serum albumin (BSA) and
      roflumilast (ROF) was explored in this study. The binding of drugs to albumin
      plays a vital role in their pharmacokinetics and pharmacodynamics in vivo. The
      mechanisms involved in the interaction between BSA and ROF was studied using
      multi-spectroscopic experimental and computational approaches. Materials and
      methods: Spectrofluorometric experiments were used to determine the method of
      quenching involved and the conformational changes in the BSA. UV-visible
      spectroscopy synchronous and three-dimensional fluorescence spectroscopy were
      used to further explore the binding interaction mechanism. Results: The results
      suggested that the intrinsic fluorescence of BSA was quenched due to the
      formation of a static complex between ROF and BSA. Conformational changes in BSA
      were determined based on its interaction with ROF. The thermodynamic results
      suggested that the interaction between ROF and BSA was spontaneous and a
      hydrophobic interaction occurred between them. Site I of BSA was suggested as the
      site of interaction between ROF and BSA based on the site marker experiments.
      Conclusion: The molecular simulation results and the experimental outcomes were
      complimentary to each other and helped to identify the binding site and nature of
      bonds involved in the interaction between ROF and BSA.

PMID- 30214152
TI  - Efficient drug delivery of beta-estradiol encapsulated in Zn-metal-organic
      framework nanostructures by microwave-assisted coprecipitation method.
AB  - Metal-organic frameworks (MOFs) are structures made up of inorganic nodes, which
      can be either single ions or clusters of ions and organic linkers. This study
      reports on a novel processing route for producing beta-estradiol encapsulated in
      Zn-MOF nanocomposites by microwave-assisted coprecipitation as a facile and fast
      method. Zn-MOF nanocomposites were synthesized with the aid of Zn(OAc)2?2H2O and
      2,6-pyridine dicarboxylic acid ammonium as an organic ligand. Furthermore, we
      studied encapsulated beta-estradiol which is one of the most important classes of
      estrogenic compounds that are used in the treatment of prostate cancer and breast
      cancer. The effects of beta-estradiol concentration and microwave irradiation on
      the morphology, particle size, distribution, and in vitro photoluminescence
      spectroscopy experiments of beta-estradiol entrapped in Zn-MOF nanocomposites
      were characterized by X-ray diffraction, scanning electron microscopy,
      transmission electron microscopy, ultraviolet-visible spectroscopy, Fourier
      transform infrared spectroscopy, and Brunauer-Emmett-Teller spectroscopy. These
      nanostructures can be a good option for thawing hydrophilic and hydrophobic drugs
      over time. Zn-MOF nanocomposites with high porosity, total pore volume (0.04665
      cm3g-1), and nanostructures have provided the platform to load beta-estradiol
      such as low soluble drugs. Maximum of drug release was about 82% at pH 8.9 after
      8 h.

PMID- 30214153
TI  - A novel multifunctional anti-CEA-IL15 molecule displays potent antitumor
      activities.
AB  - Introduction: Interleukin-15 (IL-15) is an immunomodulatory cytokine. It can
      activate and expand cytotoxic CD8 T lymphocytes and natural killer cells, leading
      to potent antitumor effects. Various forms of IL-15 are now in different stages
      of development for cancer immunotherapy. One of the major issues with IL-15 or
      IL15-IL15Ralpha fusion is high toxicity due to systemic activation of immune
      cells. Materials and methods: In this study, we engineered a nanobody-cytokine
      fusion molecule, anti-CEA-IL15, in which an anti-CEA nanobody was linked to an
      IL15Ralpha-IL15 fusion. The nanobody-cytokine fusion exhibited multiple
      mechanisms to kill tumor cells, including promoting immune cell proliferation and
      directing antibody-dependent cytotoxicity against CEA-positive tumor cells.
      Results: In xenograft models, anti-CEA-IL15 was localized in the tumor
      microenvironment and exhibited more potent antitumor activities than non
      targeting IL-15, supporting potential application of this multifunctional fusion
      molecule in tumor immunotherapy. Conclusion: We generated and validated a
      tumortargeting fusion protein, anti-CEA-IL15, which has potent cytokine activity
      to activate and mobilize the immune system to fight cancer cells. Such strategies
      may also be applied to other cytokines and tumor-targeting molecules to increase
      antitumor efficacy.

PMID- 30214154
TI  - Inhibiting eEF-2 kinase-mediated autophagy enhanced the cytocidal effect of AKT
      inhibitor on human nasopharyngeal carcinoma.
AB  - Aim: Our previous research showed that AKT inactivation via small molecule
      inhibitors did not induce significant apoptosis, but rather markedly increased
      autophagy in nasopharyngeal carcinoma (NPC). The purpose of the current study was
      to determine whether autophagy inhibition can enhance the anticancer efficacy of
      an AKT inhibitor (MK-2206). Materials and methods: NPC cell lines CNE-2 (Epstein
      Barr virus negative) and C666-1 (Epstein-Barr virus positive) were used to
      conduct the research. Autophagy induction effects were evaluated via Western
      blotting. Eukaryotic elongation factor-2 (eEF-2) kinase was specifically and
      stably knocked down using shRNA. The growth and proliferation of the cells were
      assessed by Cell Counting Kit-8. In CNE-2 xenograft tumors, the antitumor effects
      of an AKT inhibitor (MK-2206) combined with an eEF-2 kinase inhibitor (NH125)
      were tested. Results: MK-2206 induced eEF-2 kinase-dependent autophagy in NPC
      cell lines. Knockdown of eEF-2 kinase using shRNA blunted the autophagy activated
      by MK-2206. Compared with treatment with MK-2206 alone, shRNA or NH125 suppressed
      eEF-2 kinase and increased the growth-inhibitory effect of MK-2206 on the human
      NPC cell lines. The synergistic effects of eEF-2 kinase inhibition and MK-2206
      were similar to those of the combination of hydroxychloroquine and MK-2206.
      Moreover, NH125 showed good synergistic effects with MK-2206 in vivo. Conclusion:
      eEF-2 kinase-mediated autophagy induced by AKT inhibition played a protective
      role in NPC cells. Inhibition of eEF-2 kinase may be an effective method for
      increasing the efficacy of an AKT inhibitor such as MK-2206 in NPC.

PMID- 30214155
TI  - Profile of pitolisant in the management of narcolepsy: design, development, and
      place in therapy.
AB  - Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness
      and rapid eye movement sleep dysregulation, manifesting as cataplexy and sleep
      paralysis, as well as hypnagogic and hypnopompic hallucinations. Disease onset
      may occur at any age, although adolescents and young adults are mainly affected.
      Currently, the diagnosis delay ranges from 8 to 10 years and drug therapy may
      only attenuate symptoms. Pitolisant is a first-in-class new drug currently
      authorized by the European Medicines Agency to treat narcolepsy with or without
      cataplexy in adults and with an expanded evaluation for the treatment of
      neurologic diseases such as Parkinson's disease and epilepsy. This article
      reviews the pharmacokinetic and pharmacodynamic profile of pitolisant,
      highlighting its effectiveness and safety in patients with narcolepsy. We
      performed a systematic review of the literature using PubMed, Embase, and Google
      Scholar. We report on the efficacy and safety data of pitolisant in narcoleptic
      patients regarding cataplexy episodes and subjective and objective daytime
      sleepiness. The development program of pitolisant was characterized by eight
      Phase II/III studies. One proof-of-concept study followed by two pivotal studies,
      three randomized controlled trials, and two open studies were evaluated. Our
      review confirmed the effectiveness of pitolisant in treating major clinically
      relevant narcolepsy symptoms, including cataplexy, as compared to placebo. In
      addition, pitolisant revealed a safe profile when compared with placebo and
      active comparators. Headache, insomnia, and nausea were the prominent side
      effects. Further long-term randomized controlled trials comparing the efficacy of
      pitolisant with active comparators (ie, modafinil and sodium oxybate) may clarify
      its real place in therapy and its possible use as a first-line agent on the basis
      of its safety and tolerability.

PMID- 30214156
TI  - Asenapine pharmacokinetics and tolerability in a pediatric population.
AB  - Purpose: This study aimed to characterize the pharmacokinetic (PK) properties,
      safety, and tolerability of asenapine, and to develop a population PK model in
      pediatric patients with schizophrenia, bipolar disorder, or other psychiatric
      disorders. Methods: Two Phase I multiple ascending-dose studies were conducted to
      evaluate the PK, safety, and tolerability of sublingual asenapine in pediatric
      patients (age 10-17 years) with schizophrenia or bipolar I disorder. Patients
      received asenapine 1-10 mg twice daily for up to 12 days. PK parameters (maximum
      concentration [Cmax], area under the curve from 0 to 12 hours [AUC0-12], time to
      Cmax [Tmax], and half-life) were summarized for asenapine with descriptive
      statistics, and safety parameters were collected. A population PK model, which
      included the two Phase I studies and two additional Phase III efficacy studies
      (asenapine 2.5-10 mg twice daily for up to 8 weeks, age 10-17 years), was
      developed using nonlinear mixed-effect modeling based on a previously developed
      adult PK model. The final model was used in simulations to obtain asenapine
      exposure estimates across pediatric subgroups and to determine if intrinsic
      covariates warrant dose adjustments. Results: The PK of asenapine showed rapid
      absorption (Tmax ~1 hour) with an apparent terminal half-life between 16 and 32
      hours. Increases in mean Cmax and AUC0-12 appeared to be dose-proportional in one
      study and near dose-proportional in the second study. Steady state was attained
      within 8 days. The most frequently occurring treatment-emergent adverse events
      were dysgeusia, sedation, and oral hypoesthesia. Simulation-based estimates of
      Cmax and AUC0-12 were similar for pediatric and adult patients; age, body-mass
      index, race, and sex were not associated with changes in asenapine exposure.
      Conclusion: Asenapine was generally safe and well tolerated in pediatric patients
      aged 10-17 years. PK and safety data were similar to that observed in the adult
      population. Intrinsic factors had no significant impact on asenapine exposure,
      indicating there is no need for dose adjustments in the pediatric population.

PMID- 30214157
TI  - The total alkaloids from Coptis chinensis Franch improve cognitive deficits in
      type 2 diabetic rats.
AB  - Background: Coptis chinensis Franch is extensively used in traditional Chinese
      medicine to treat diabetes and dementia. Alkaloids are the main active
      ingredients of C. chinensis. Purpose: This study was designed to probe the
      effects and possible mechanisms of the total alkaloids from C. chinensis (TAC) on
      cognitive deficits in type 2 diabetic rats. Methods: Cognitive deficits were
      induced in rats by streptozotocin and high glucose/high fat diet. After treatment
      with TAC (80, 120, and 180 mg/kg) for 24 weeks, the behavioral parameters of each
      rat were assessed by Morris water maze and Y-maze tests. The indexes of glucose
      and lipid metabolism, pathological changes of brain tissue, and the
      phosphorylation levels of insulin signaling related proteins were also evaluated.
      Results: The type 2 diabetic rats showed significantly elevated levels of fasting
      blood glucose, glycosylated hemoglobin and glycosylated serum protein, as well as
      apolipoprotein B, free fatty acid, triglyceride and total cholesterol but
      decreased the content of apolipoprotein A1, and TAC treatment dose-dependently
      reversed these abnormal changes. Furthermore, the behavioral results showed that
      TAC alleviated the cognitive deficits in type 2 diabetic rats. Moreover,
      immunohistochemical and histopathologic examinations indicated that the diabetic
      rats showed significant Abeta deposition, and neuronal damage and loss, which can
      be reversed by TAC treatment. The western blot results showed that TAC treatment
      markedly increased the phosphorylation of IRS, PI3K, and Akt, and inhibited the
      overactivation of GSK3beta in the brain of type 2 diabetic rats. Conclusion:
      These findings conclude that TAC prevents diabetic cognitive deficits, most
      likely by ameliorating the disorder of glucose and lipid metabolism, attenuating
      Abeta deposition, and enhancing insulin signaling.

PMID- 30214158
TI  - Fasudil inhibits actin polymerization and collagen synthesis and induces
      apoptosis in human urethral scar fibroblasts via the Rho/ROCK pathway.
AB  - Purpose: To examine the effects and mechanism of action of fasudil on
      cytoskeletal polymerization, collagen synthesis, and apoptosis in fibroblasts
      derived from human urethral scar tissue. Materials and methods: Fibroblasts
      treated with or without transforming growth factor beta1 (TGF-beta1, 10 ng/mL)
      were incubated with fasudil (12.5, 25, 50 MUmol/L) for 24 hours. Quantitative
      real-time polymerase chain reaction and Western blotting were used to determine
      the expression of Arp2, Arp3, WASP, and WAVE2. Collagen I and III protein levels
      were also evaluated by Western blotting. The filamentous actin cytoskeleton was
      examined by immunofluorescence and epifluorescence microscopy. An Annexin V
      FITC/PI staining assay was used to investigate apoptosis. Results: TGF-beta1
      dependent induction of actin polymerization and collagen synthesis and promotion
      of apoptosis were dose dependent. When compared with untreated controls, fasudil
      significantly decreased the expression of Arp2, Arp3, WASP, WAVE2, Collagen I,
      and Collagen III in cells treated with or without TGF-beta1. Fasudil also
      promoted apoptosis in cells, irrespective of TGF-beta1 treatment. Conclusion:
      Irrespective of TGF-beta1 activation status, fasudil suppressed actin
      polymerization and collagen synthesis and induced apoptosis in human urethral
      scar fibroblasts via the Rho/ROCK signaling pathway.

PMID- 30214159
TI  - Changes in adherence and associated factors among patients on newly introduced
      prostaglandin analog and timolol fixed-combination therapy.
AB  - Purpose: We investigated patient adherence and factors related to a newly
      introduced prostaglandin analog and timolol fixed-combination eye drops (PGTFC).
      Patients and methods: The Glaucoma Research on Adherence to fixed-Combination Eye
      drops in Japan (GRACE) study group performed a nationwide prospective
      questionnaire survey. Participants in this study were patients with glaucoma who
      were scheduled to receive any type of PGTFC for the first time. The participants
      answered a questionnaire on the day of PGTFC introduction and again at a return
      visit 4-6 weeks after PGTFC introduction. The physicians in charge were asked to
      complete a separate questionnaire on the day of PGTFC introduction. One of two
      leaflets was randomly delivered to each participant before the description of the
      PGTFC. One leaflet explained how to correctly instill the eye drops, and the
      other explained the clinical meaning of intraocular pressure reduction in
      addition to explaining how to correctly instill the eye drops. Nonadherence was
      defined as forgetting to instill the eye drops one or more times during the week
      before the return visit. Results: In total, 3,597 patients (age, 68.4+/-12.2
      years) met the study protocol requirements. PGTFC introduction significantly
      reduced the number of antiglaucoma eye drops from 1.93+/-0.78 to 1.34+/-0.54
      (P<0.0001) and significantly improved adherence (P<0.00001). Factors
      significantly associated with nonadherence at the return visit included a history
      of nonadherence as reported by either the patient or their physician before
      introduction, acceptable instillation times as reported by the patient, and
      burdensome eye drop instillation as reported by the patient. No significant
      difference was observed between the two leaflets in terms of their effects on
      adherence. Conclusion: PGTFC significantly improved adherence and some of the
      factors that were significantly associated with adherence. Registration number:
      UMIN000013696.

PMID- 30214160
TI  - Disease-related information requirements in patients with Crohn's disease.
AB  - Aim: To explore the demands for different disease-related information and the
      acceptance of various information sources in patients with Crohn's disease (CD).
      Methods: This study included 159 patients with CD and was conducted from April
      2017 to December 2017 in our hospital. We obtained the demographic
      characteristics of the patients and used the modified information demands
      questionnaire to assess patients' disease information demands, covering 4 aspects
      which include general knowledge, fertility, clinical treatment, and daily
      management. Then, we analyzed the factors associated with the information demand.
      In addition, we studied the patients' acceptance of different information
      sources. Results: The disease-related information demands of patients with CD are
      generally high. Female patients, young patients, and patients with plans to have
      children have significantly higher information demands concerning fertility. The
      information demands in clinical treatment are higher in young patients. Patients
      living in the countryside and patients with a short disease duration have high
      information demands concerning life management. The patients' acceptance of
      different information sources is variable. Doctor-mediated guidance, brochures,
      and videos are the top 3 patient choices for information sources. Conclusion:
      Patients' information demands concerning many aspects of CD are generally high.
      Certain demands are significantly associated with the demographic characteristics
      of the patients. Doctor-mediated guidance, brochures, and videos are the top 3
      patient choices for information sources. Therefore, corresponding education
      programs can be developed to improve the physical and psychological health of CD
      patients in the future.

PMID- 30214161
TI  - The Chinese version of the Coronary Artery Disease Education Questionnaire-II
      (CADEQ-II): translation and validation.
AB  - Objectives: It is necessary to assess disease-related knowledge in patients with
      coronary artery disease (CAD) for tailored patient education; however there is a
      lack of a well-validated measurement in China. The objective of this study was to
      translate and validate a Chinese version of the Coronary Artery Disease Education
      Questionnaire-II (CADEQ-II). Methods: The Chinese version of CADEQ-II was
      translated and culturally adapted. Then, it was tested for psychometric
      properties through a convenient sampling. Content validity was examined based on
      a panel of five experts. The item difficulty index and item discrimination index
      were calculated to assess the item difficulty and item discrimination. Internal
      consistency reliability was measured with the Cronbach's alpha coefficient.
      Criterion-related validity was established through comparing scores in patients
      with different education levels. Construct validity was assessed through
      confirmatory factor analysis (CFA). Results: The Chinese version of the CADEQ-II
      was finalized after deleting three items and modifying two items from the
      original version. Three hundred and sixteen participants completed the whole
      questionnaire. Content validity index of the whole questionnaire was 0.87. The
      Cronbach's alpha coefficient of the overall questionnaire was 0.907. The
      significant difference of the knowledge scores among patients with different
      education levels supported criterion-related validity. CFA confirmed the proposed
      four-factorial structure of the questionnaire. Conclusion: The Chinese version of
      CADEQ-II had an acceptable reliability and validity among Chinese patients with
      CAD. It could be used to develop individualized health education for Chinese
      patients with CAD. Also, it could serve as a suitable outcome measurement to
      evaluate the effectiveness of education interventions related to CAD.

PMID- 30214162
TI  - Use patterns of over-the-counter (OTC) medications and perspectives on OTC
      medications among Korean adult patients with chronic diseases: gender and age
      differences.
AB  - Background: A number of symptomatic patients tend to use over-the-counter (OTC)
      medications and prescription medications. OTC medications can be easily obtained
      in pharmacies for self-treatment, but using OTC medications is not always safe
      and beneficial for patients. The aims of this study were to examine the use
      patterns of OTC medications and assess patients' perspectives regarding the use
      of OTC medications in Korean patients with chronic diseases. Patients and
      methods: A descriptive, cross-sectional survey was carried out with Korean
      patients who visited the community pharmacy, located at the southern region of
      South Korea, during September 2015. Results: A total of 345 patients participated
      in this survey. Approximately 64% of Korean survey respondents reported that they
      had used OTC drugs. The most commonly used OTC medications were antipyretics,
      analgesics and anti-inflammatory drugs. The perception level of Korean consumers
      on adverse drug reactions and drug-drug interactions from OTC medications was
      relatively low. Although OTC package leaflets are a main source of information
      about OTC medications, Korean consumers' level of reading OTC package leaflets
      was relatively low. Conclusion: Based on these results, this study can serve as a
      meaningful starting point for interventions of health care professionals
      regarding OTC medications in South Korea. In particular, pharmacists should
      inform their consumers of drug-related problems from OTC drugs during
      consultation with the consumers; however, information about OTC drugs should be
      tailored to consumer information needs with the consideration of his or her
      circumstance. It is somewhat difficult to generalize the results from this study
      to other regions of South Korea since most of the respondents were probably
      residents of a small rural city located in the southern region of South Korea.

PMID- 30214163
TI  - A cohort study to evaluate infection prevention protocol in pediatric trauma
      patients with blunt splenic injury in a Dutch level 1 trauma center.
AB  - Purpose: Asplenic patients are at increased risk for the development of
      overwhelming postsplenectomy infection (OPSI) syndrome. It is believed that
      adequate immunization, antimicrobial prophylaxis, as well as appropriate
      education concerning risks on severe infection lead to the decreased incidence of
      OPSI. The aim of this study was to analyze the methods used to prevent OPSI in
      trauma patients splenectomized before the age of 18. Patients and methods: A
      retrospective, single-center study of all pediatric patients sustaining blunt
      splenic injury (BSI) managed at our level 1 trauma center from January 1979 to
      March 2012 was performed. A questionnaire was sent to all the included patients
      to determine the level of knowledge concerning infection risks, the use of
      antibiotics, and compliance to vaccination recommendations. Furthermore, we
      investigated whether the implementation of guidelines in 2003 and 2011 resulted
      in higher vaccination rates. Results: We included 116 children with BSI. A total
      of 93 completed interviews were eligible for analysis, resulting in a total
      response rate of 80% and 1,116 patient years. Twenty-seven patients were
      splenectomized, and 66 patients were treated by a spleen preserving therapy
      (including embolization). Only two out of 27 splenectomized patients were
      adequately vaccinated, five patients without a spleen used prophylactic
      antibiotics, and about half of the asplenic patients had adequate knowledge of
      the risk that asplenia entails. A total of 22/27 splenectomized patients were
      neither adequately vaccinated nor received prophylactic antibiotics. There was no
      OPSI seen in our study population during the 1,116 follow-up years. Conclusion:
      The vaccination status, the level of knowledge concerning prevention of an OPSI,
      and the use of prophylactic antibiotics are suboptimal in pediatric patients
      treated for BSI. Therefore, we created a new follow-up treatment guideline to
      have adequate preventive coverage to current standards for these patients.

PMID- 30214164
TI  - Patient preferences for rheumatoid arthritis treatments: results from the
      national cross-sectional LERACS study.
AB  - Introduction: To investigate the treatment preferences of patients with
      rheumatoid arthritis (RA) and determine whether these preferences are related to
      specific disease characteristics. Method: A national survey was designed to
      collect demographic, disease, treatment, and preference data on RA patients
      enrolled in 7 private and university hospital clinics in Lebanon. Associations
      between patient factors and treatment preferences for RA were analyzed by chi2 or
      Mann-Whitney U test. Results: A total of 693 patients (83% female; 67% aged 41-70
      years) consulting 7 trained rheumatologists completed the survey. Most patients
      (80%) had established RA >24 months, and approximately one-third (34%) were in
      remission according to the disease activity score in 28 joints (DAS28). Most
      (87%) were receiving oral agents (60% oral only). Almost two-thirds of patients
      (64%) expressed a preference for oral treatments, and more than half (53%) ranked
      doctor's advice as the most influential factor when choosing treatment. In
      univariable analysis, health coverage, radiographic damage, disease duration,
      current therapy, and previous side effects were significantly associated with
      treatment preference. In multivariable analyses, only radiographic damage and
      current route of administration were independently associated with preference
      (both P<0.001), with patients with no radiographic damage and those on oral-only
      therapy being more likely to prefer oral agents. Conclusion: RA patients
      expressed a preference for oral rather than subcutaneous/intravenous-administered
      drugs. Understanding patients' preferences may help to inform policymaker
      decisions.

PMID- 30214165
TI  - Treatment preferences among Japanese women with dysmenorrhea: results from a
      discrete choice experiment study.
AB  - Purpose: To examine patient preferences for oral and intrauterine system
      treatments for dysmenorrhea in Japan. Patients and methods: A discrete choice
      experiment was conducted to assess the willingness to accept trade-offs among
      hypothetical treatment profiles. An internet-based survey was administered to
      women 18-49 years of age who self-reported a dysmenorrhea diagnosis or
      experienced dysmenorrhea at least once in the past 6 months (N=309). Choice
      questions included pairs of treatments presented with different attributes: mode
      of administration, reduction in bleeding after 6 months, chance of symptoms
      becoming "improved", nausea, weight gain, irregular bleeding, and risk of venous
      thromboembolism. Relative importance (RI) estimates were computed. Results: The
      mean respondent age was 35.8 years (standard deviation =7.0), and 85 women
      (27.5%) reported that they had previously used hormonal therapy for dysmenorrhea.
      Treatment preference was most strongly associated with mode of administration
      (RI=49.8%), followed by chance of irregular bleeding (RI=17.3%). In contrast,
      treatment preference was most weakly associated with chance of weight gain
      (RI=2.4%) and reduction in bleeding after 6 months (RI=0.8%). Respondents
      preferred oral treatments: for twice-daily regimen, odds ratio (OR)=4.90; for
      once-daily fixed cyclic regimen, OR=4.20; and for once-daily flexible extended
      regimen, OR=2.44; whereas for intrauterine system, OR=0.02 (p<0.001 for all).
      Those with prior hormonal therapy experience exhibited the same pattern.
      Conclusion: Mode of administration factored heavily in dysmenorrhea treatment
      preferences. Women of reproductive age preferred oral medication, especially
      twice-daily regimen and once-daily fixed cyclic regimen. Findings can potentially
      help to improve physician-patient communication and treatment decision making.
      Physicians should consider factors that can influence patient preference to
      optimize treatment acceptance and adherence.

PMID- 30214166
TI  - Distribution characteristics and factors influencing oral warfarin adherence in
      patients after heart valve replacement.
AB  - Purpose: Oral warfarin anticoagulation is a long-term treatment that is required
      after heart valve replacement. This treatment can prevent serious complications,
      such as embolism, thereby increasing patients' postoperative survival rates and
      quality of life. Patients treated with artificial mechanical heart valve
      replacement were followed up over the phone at different times after the
      procedure, which is an effective method for preventing accidents related to
      postoperative oral warfarin anticoagulation. Our goal was to determine a method
      for providing theoretical guidance to patients on oral warfarin anticoagulation
      following heart valve replacement. Patients and methods: The participants of this
      study were patients who received artificial mechanical heart valve replacements
      and were followed up for 2 years after the procedure. Patient adherence to
      medical advice was calculated, and the distribution characteristics of adherence
      to prescribed timing, prescribed dose, and regular clinical follow-up among
      patients of both sexes and of different ages, regions, and educational levels
      attained were compared. Results: Univariate and multifactorial logistic
      regression analyses were used to evaluate the factors influencing adherence. Our
      analyses showed that adherence to oral warfarin anticoagulation in patients after
      heart valve replacement is influenced by sex, age, residential location, and
      educational attainment. The medication habits of patients can be evaluated
      accordingly via phone follow-up. As such, dose adjustment recommendations can be
      provided, significantly increasing the adherence to oral warfarin anticoagulation
      in patients after heart valve replacement. Conclusion: Adherence to oral warfarin
      anticoagulation among patients after heart valve replacement is affected by sex,
      age, type of residence, and educational level, as well as adherence to clinical
      follow-up over the phone. The follow-up sessions help establish good doctor
      patient communication, which is critical for timely medication guidance, thus
      shortening medication administration delays and decreasing the overall length of
      therapy.

PMID- 30214167
TI  - Dental professionalism and influencing factors: patients' perception.
AB  - Background: Professionalism was recognized as a fundamental competency of
      medical/dental practice at the beginning of the twenty-first century.
      Organizations and experts published several definitions of professionalism, but
      research on patients' perception of professionalism has been limited. To address
      this gap in literature, this study explored dental patients' perception of dental
      professionalism, and then compared their perception with that of dental
      professionals. Methods: Of the 800 questionnaires that were distributed to dental
      patients in public and private clinics and hospitals, 504 were returned and were
      used in the analysis. A factor analysis was used to generate themes and sub
      themes. Independent sample t-tests were performed to compare two independent
      groups and the ANOVA tests to compare means in more than two independent groups.
      Results: A factor analysis revealed four factors: excellence and communication
      skills; humanism, commitment, and service mindedness; competence in practice; and
      dentists' duties and management skills. Adherence to sterilization and infection
      control rules and procedures; personal hygiene and clean professional attire;
      good communication skills; diagnostic and clinical judgment and provision of the
      most efficient dental treatment; and ethical decisions and ethical care were
      ranked as the first five most important elements of dental professionalism from
      patients' perspective. Several demographic factors showed significant differences
      in perception. Conclusion: Patients' and dentists' perception of dental
      professionalism and professional behavior vary in certain aspects. These
      differences must be addressed to ensure excellence of dental service. Dental
      professionals must also be aware of the personal factors that affect a patient's
      perception of professionalism.

PMID- 30214168
TI  - Attitudes of cancer patients and their families toward disclosure of cancer
      diagnosis in Saudi Arabia: a Middle Eastern population example.
AB  - Objectives: Particularly in the Middle East, few studies have explored the
      attitude of cancer patients and their families toward cancer diagnosis disclosure
      (CDD). This study was conducted to investigate the preference and attitude of a
      sample of cancer patients and their families in Saudi Arabia toward CDD. Methods:
      We constructed a questionnaire based on previous studies. The questionnaire
      assessed preference and attitude toward CDD. Participants were recruited from the
      King Abdullah Medical City, which has one of the largest cancer centers in Saudi
      Arabia. Results: Three hundred and four cancer patients and 277 of their family
      members participated in the study. The patient group preferred CDD more than the
      family group (82.6% vs 75.3%, P<0.05). This preference is especially more evident
      toward disclosure of detailed cancer information (status, prognosis, and
      treatment) (83.6% vs 59.9%, P<0.001). In a binary logistic regression, factors
      associated with preference toward CDD included having information about cancer
      (odds ratio [OR] 1.8; 95% confidence interval [CI], 1.15-2.84) and being employed
      (OR, 1.77; 95% CI, 1-2.82) while being from the patient group was the only factor
      associated with preference toward detailed cancer information (OR, 3.25; 95% CI,
      2.11-5.05). In terms of patient reaction after CDD, "fear" was the attitude
      expected by the family group more than the patient group (56.3% vs 70.4%,
      P<0.001) while "acceptance" was the attitude anticipated by the patient group
      more than the family group (38% vs 15.2%, P<0.001). Conclusion: Patients
      preferred CDD and disclosure of related information, while their families were
      more inclined toward scarce disclosure. Family members seem to experience
      negative attitudes more than the patients themselves.

PMID- 30214169
TI  - Assessment of prescribing potentially inappropriate medications listed in Beers
      criteria and its association with the unplanned hospitalization: a cross
      sectional study in Lahore, Pakistan.
AB  - Background and objectives: Due to physiological and pharmacological variations,
      geriatrics are at high risk of experiencing life-threatening outcomes related to
      the use of potentially inappropriate medications (PIMs). Thus, the present study
      aims to evaluate prescribing practices of PIMs among elderly patients who may
      lead to unplanned hospitalization and associated risk factors. Methods: A cross
      sectional study was conducted in different hospitals of Lahore, Pakistan. The
      study population consisted of geriatric patients aged >=65 years. Data were
      collected from the medical records of geriatric patients, who attended these
      selected hospitals between December 1, 2017, and February 28, 2018. Data were
      analyzed using SPSS (IBM SPSS Statistics for Windows, Version 21.0) and Microsoft
      Excel (MS Office 2010). Results: The records of 385 geriatric patients were
      investigated. More than half (60.8%) of the patients were subjected to
      polypharmacy, which can be defined as the utilization of 5-9 drugs by the patient
      at the same time, whereas 36.4% were prescribed with one PIM and 56.4% were
      hospitalized due to PIMs. Majority of them were prescribed with PIMs including
      N02BA01 (aspirin, 32.4%), A02BC01 (omeprazole, 23.6%), A10AB02 (insulin, 17.4%),
      A02BC05 (esomeprazole, 8.5%), C08CA01 (amlodipine, 8.3%), and R06AA02
      (diphenhydramine, 5.9%). Results of regression analysis revealed that patients
      exposed to polypharmacy (OR=2.556, 95% CI=1.579-4.135, P-value<=0.001) and
      excessive polypharmacy (OR=37.828, 95% CI=4.754-300.9, P-value<=0.001) were
      significantly associated with unplanned hospitalization, whereas factors such as
      age 75-84 years (OR=0.343, 95% CI=0.156-0.756, P-value=0.008) and polypharmacy
      (OR=2.480, 95% CI=1.219-5.048, P-value=0.012) were significantly correlated with
      PIMs. Conclusion: The utilization of PIMs listed in Beers criteria among
      geriatric population can cause unplanned hospitalization. As the patients
      receiving polypharmacy are at high risk of unplanned hospitalization, so caution
      must be exercised in prescribing PIMs for elderly people.

PMID- 30214170
TI  - Gut microbiota, cognitive frailty and dementia in older individuals: a systematic
      review.
AB  - Cognitive frailty, defined as the coexistence of mild cognitive impairment
      symptoms and physical frailty phenotype in older persons, is increasingly
      considered the main geriatric condition predisposing to dementia. Recent studies
      have demonstrated that gut microbiota may be involved in frailty physiopathology
      by promoting chronic inflammation and anabolic resistance. The contribution of
      gut microbiota to the development of cognitive impairment and dementia is less
      defined, even though the concept of "gut-brain axis" has been well demonstrated
      for other neuropsychiatric disorders. The aim of this systematic review was to
      summarize the current state-of-the-art literature on the gut microbiota
      alterations associated with cognitive frailty, mild cognitive impairment and
      dementia and elucidate the effects of pre- or probiotic administration on
      cognitive symptom modulation in animal models of aging and human beings. We
      identified 47 papers with original data (31 from animal studies and 16 from human
      studies) suitable for inclusion according to our aims. We concluded that several
      observational and intervention studies performed in animal models of dementia
      (mainly Alzheimer's disease) support the concept of a gut-brain regulation of
      cognitive symptoms. Modulation of vagal activity and bacterial synthesis of
      substances active on host neural metabolism, inflammation and amyloid deposition
      are the main mechanisms involved in this physiopathologic link. Conversely, there
      is a substantial lack of human data, both from observational and intervention
      studies, preventing to formulate any clinical recommendation on this topic. Gut
      microbiota modulation of cognitive function represents, however, a promising area
      of research for identifying novel preventive and treatment strategies against
      dementia.

PMID- 30214172
TI  - Sleep onset latency is related with reduced bone mineral density in elderly
      people with insomnia: a retrospective study.
AB  - Purpose: Inconsistent outcome about association between insufficient sleep and
      bone mineral density (BMD) has been reported. The present study aimed to
      determine whether BMD was associated with score of Pittsburgh Sleep Quality Index
      (PSQI). Methods: A total of 410 patients (mean age 81.6+/-5.9 years) attending
      our hospital for evaluation of sleep were retrospectively studied. Dual-Energy X
      ray Absorptiometry was used to measure BMD and T-score at femoral neck and lumbar
      spines over L2-L4 regions. Subjective sleep status was evaluated by the PSQI
      questionnaires. The Mann-Whitney U test and chi-square analysis were used to
      compare continuous variables and categorical variables, respectively. Spearman
      correlation test was conducted to find the relationship between BMD and other
      clinical factors. Multinomial logistic regressions analysis was performed to
      analyze independent factors predicting BMD. Results: Majority of the participants
      with osteoporosis (OP) were female and had lower body mass index (BMI) and higher
      sleep onset latency score. Spearman correlation test showed that gender, BMI,
      score of total PSQI, and sleep onset latency were significantly related to BMD
      and T-score in femoral neck and lumbar region L2-L4. Finally, multinomial
      logistic regression analysis demonstrated that gender and age were independent
      factors for OP and osteopenia and that after adjustment for gender, age, and BMI,
      sleep onset latency of <15 minutes (OR: 0.38; 95% CI: 0.15-0.96; P=0.04) and 16
      30 minutes (OR: 0.37; 95% CI: 0.17-0.79; P=0.01) were less likely to have reduced
      BMD. Conclusion: There was a significant association between BMD and sleep onset
      latency, suggesting that, in elderly patients with sleep problem, BMD measurement
      and intervention for OP might be valuable.

PMID- 30214171
TI  - Frailty assessment in older adults with chronic obstructive respiratory diseases.
AB  - The number of patients with chronic obstructive pulmonary disease (COPD) has been
      rising with continued exposure to environmental risk factors and aging of
      populations around the world. Frailty is a geriatric syndrome with a decline in
      physiological reserve and often coexists with chronic diseases such as COPD.
      Frailty is an independent risk factor for the development and progression of
      COPD, and COPD can lead to frailty; treating one might improve the other. Thus,
      there is an increasing interest in the assessment of frailty in patients with
      COPD. Furthermore, early identification and assessment of frailty in patients
      with COPD may affect the choice of intervention and improve its effectiveness.
      Based on the current literature, the intent of this review was to summarize and
      discuss frailty assessment tools used for COPD patients and the relevant clinical
      practices for predicting outcomes. We ascertain that using suitable frailty
      assessment tools could facilitate physicians to screen and stratify physically
      frail patients with COPD. Screening appropriately targeted population can achieve
      better intervention outcomes and pulmonary rehabilitation among frail COPD
      patients.

PMID- 30214173
TI  - Von Willebrand disease in the elderly: clinical perspectives.
AB  - Von Willebrand disease (VWD) is an inherited bleeding disorder that affects up to
      1% of the population. In most cases, VWD results from a mutation in the von
      Willebrand Factor (VWF) gene, which alters the amount and function of VWF, a key
      glycoprotein in both primary and secondary hemostasis. A comprehensive analysis
      of patients with VWD should include VWF activity, antigen levels, platelet
      function, and a careful bleeding history. Treatment options include
      antifibrinolytics, desmopressin, and VWF replacement therapy. VWF levels
      fluctuate due to age, stress, environmental exposures, and pharmacologic
      treatment. Treatment guidelines exist to treat and prevent bleeding for patients
      undergoing surgery and medical procedures, but often these must be reevaluated in
      the setting of age-related comorbidities including cardiovascular events, venous
      thrombosis, and malignancy. In addition, many age-related complications are
      associated with a secondary acquired von Willebrand syndrome (AVWS), including
      malignancies, hypothyroidism, cardiovascular diseases, and cardiac replacement
      devices. The current literature is limited by a lack of older patients in
      clinical trials. Larger studies are needed to determine if age-related
      comorbidities affect VWD patients at different frequencies than the general
      elderly population. There is also a significant need for registry-based studies
      to evaluate many age-related comorbidities in VWD patients.

PMID- 30214176
TI  - Prediction of severe acute exacerbation using changes in breathing pattern of
      COPD patients on home noninvasive ventilation.
AB  - Introduction: Acute exacerbation of COPD (AECOPD) is associated with poor
      outcome. Noninvasive ventilation (NIV) is recommended to treat end-stage COPD. We
      hypothesized that changing breathing pattern of COPD patients on NIV could
      identify patients with severe AECOPD prior to admission. Methods: This is a
      prospective monocentric study including all patients with COPD treated with long
      term home NIV. Patients were divided in two groups: a stable group in which
      patients were admitted for the usual respiratory review and an exacerbation group
      in which patients were admitted for inpatient care of severe AECOPD. Data from
      the ventilator were downloaded and analyzed over the course of the 10 days that
      preceded the admission. Results: A total of 62 patients were included: 41 (67%)
      in the stable group and 21 (33%) in the exacerbation group. Respiratory rate was
      higher in the exacerbation group than in the stable group over the 10 days
      preceding inclusion (18.2+/-0.5 vs 16.3+/-0.5 breaths/min, respectively)
      (P=0.034). For 2 consecutive days, a respiratory rate outside the interquartile
      limit of the respiratory rate calculated over the 4 preceding days was associated
      with an increased risk of severe AECOPD of 2.8 (95% CI: 1.4-5.5) (P<0.001). This
      assessment had the sensitivity, specificity, positive predictive, and negative
      predictive values of 57.1, 80.5, 60.0, and 78.6% respectively. Over the 10 days'
      period, a standard deviation (SD) of the daily use of NIV >1.0845 was associated
      with an increased risk of severe AECOPD of 4.0 (95% CI: 1.5-10.5) (P=0.001). This
      assessment had the sensitivity, specificity, positive predictive, and negative
      predictive values of 81.0, 63.4, 53.1, and 86.7%, respectively. Conclusion: Data
      from NIV can identify a change in breathing patterns that predicts severe AECOPD.

PMID- 30214174
TI  - Differential effects of a computerized cognitive stimulation program on older
      adults with mild cognitive impairment according to the severity of white matter
      hyperintensities.
AB  - Objective: This study aimed to explore whether a computerized cognitive
      stimulation program (CCS) induced differential effects in older adults with mild
      cognitive impairment (MCI) according to the severity of white matter
      hyperintensities (WMH), which are associated with cognitive impairment and
      increased risk of progression to Alzheimer's disease because of the damage they
      cause to cortical and subcortical networks. Patients and methods: Twenty-nine MCI
      patients with no or little WMH (MCI-non-WMH) and 22 MCI patients with moderate or
      severe WMH (MCI-WMH) attended a 24-session CCS program (two sessions per week for
      a duration of 3 months) focused on executive functions, attention, and processing
      speed. Cognitive and psychosocial assessments were performed at baseline,
      postintervention, and 3 months after the intervention. Results: Both groups
      improved on several cognitive measures after the intervention. However, the MCI
      non-WMH group improved on a higher number of cognitive measures than the MCI-WMH
      group. At postintervention assessment, CCS had a more beneficial effect on the
      MCI-non-WMH group than on the MCI-WMH group with regard to improving categorical
      fluency (4.6+/-6.8 vs 0.4+/-6.4; effect size=0.37; p=0.002). During the 3-month
      follow-up assessment, significantly higher score improvements were observed in
      the MCI-non-WMH group for the paired-associate learning test (6.4+/-3 vs 4.7+/
      3.5 points; effect size=0.43; p=0.005) as well as categorical fluency (3.8+/-7.8
      vs -0.7+/-6 points; effect size=0.55; p=0.0003). Conclusions: These findings
      suggest that WMH severity was related to cognitive improvement induced by a CCS
      program and highlight the importance of considering WMH in interventional studies
      on subjects with MCI.

PMID- 30214177
TI  - Inhaled corticosteroids for chronic obstructive pulmonary disease: what is their
      role in therapy?
AB  - Inhaled corticosteroids (ICSs) are a mainstay of COPD treatment for patients with
      a history of exacerbations. Initial studies evaluating their use as monotherapy
      failed to show an effect on rate of pulmonary function decline in COPD, despite
      improvements in symptoms and reductions in exacerbations. Subsequently, ICS use
      in combination with long-acting beta2-agonists (LABAs) was shown to provide
      improved reductions in exacerbations, lung function, and health status. ICS-LABA
      combination therapy is currently recommended for patients with a history of
      exacerbations despite treatment with long-acting bronchodilators alone. The
      presence of eosinophilic bronchial inflammation, detected by high blood
      eosinophil levels or a history of asthma or asthma-COPD overlap, may define a
      population of patients in whom ICSs may be of particular benefit. Prospective
      clinical studies to determine an appropriate threshold of eosinophil levels for
      predicting the beneficial effects of ICSs are needed. Further study is also
      required in COPD patients who continue to smoke to assess the impact of cell- and
      tissue-specific changes on ICS responsiveness. The safety profile of ICSs in COPD
      patients is confounded by comorbidities, age, and prior use of systemic
      corticosteroids. The risk of pneumonia in patients with COPD is increased,
      particularly with more advanced age and worse disease severity. ICS-containing
      therapy also has been shown to increase pneumonia risk; however, differences in
      study design and the definition of pneumonia events have led to substantial
      variability in risk estimates, and some data indicate that pneumonia risk may
      differ by the specific ICS used. In summary, treatment with ICSs has a role in
      dual and triple therapy for COPD to reduce exacerbations and improve symptoms.
      Careful assessment of COPD phenotypes related to risk factors, triggers, and
      comorbidities may assist in individualizing treatment while maximizing the
      benefit-to-risk ratio of ICS-containing COPD treatment.

PMID- 30214175
TI  - Lactobacillus helveticus (ATCC 27558) upregulates Runx2 and Bmp2 and modulates
      bone mineral density in ovariectomy-induced bone loss rats.
AB  - Purpose: Osteoporosis is one of the major health concerns among the elderly
      population, especially in postmenopausal women. Many menopausal women over 50
      years of age lose their bone density and suffer bone fractures. In addition, many
      mortality and morbidity cases among the elderly are related to hip fracture. This
      study aims to investigate the effect of Lactobacillus helveticus (L. helveticus)
      on bone health status among ovariectomized (OVX) bone loss-induced rats. Methods:
      The rats were either OVX or sham OVX (sham), then were randomly assigned into
      three groups, G1: sham, G2: OVX and G3: OVX+L. helveticus (1 mL of 108-109 colony
      forming units). The supplementation was force-fed to the rats once a day for 16
      weeks while control groups were force-fed with demineralized water. Results: L.
      helveticus upregulated the expression of Runx2 and Bmp2, increased serum
      osteocalcin, bone volume/total volume and trabecular thickness, and decreased
      serum C-terminal telopeptide and total porosity percentage. It also altered bone
      microstructure, as a result increasing bone mineral density and bone strength.
      Conclusion: Our results indicate that L. helveticus attenuates bone remodeling
      and consequently improves bone health in OVX rats by increasing bone formation
      along with bone resorption reduction. This study suggests a potential therapeutic
      effect of L. helveticus (ATCC 27558) on postmenopausal osteoporosis.

PMID- 30214178
TI  - Relationship between obstructive lung disease and non-alcoholic fatty liver
      disease in the Korean population: Korea National Health and Nutrition Examination
      Survey, 2007-2010.
AB  - Purpose: Previous studies have shown that progressive forms of non-alcoholic
      fatty liver disease (NAFLD) occur frequently in patients with obstructive lung
      disease (OLD). However, few studies have written about this relationship. This
      study aimed to investigate the relationship between OLD and NAFLD. Subjects and
      methods: The Korea National Health and Nutrition Examination Survey is a national
      population-based, cross-sectional surveillance program that was initiated to
      assess the health and nutritional status of the Korean population. From 2007 to
      2010, 11,738 subjects were enrolled. The subjects were defined as having NAFLD
      when they had scores higher than -0.640 in a NAFLD liver fat score prediction
      model, which was a previously validated prediction score. Individuals with forced
      expiratory volume in one second/forced vital capacity <0.7 were considered to
      have OLD. The subjects were divided into non-OLD and OLD groups and non-NAFLD and
      NAFLD groups. All analyses were performed using sample weighting using the
      complex samples plan. Results: The prevalences of NAFLD and OLD were 30.2% and
      8.9%, respectively. Although not statistically significant, subjects in the NAFLD
      group involved a higher tendency of having OLD than did those in the non-NAFLD
      group (8.5% vs 10.0%, respectively, P=0.060). Subjects with OLD showed a higher
      tendency to have NAFLD than non-OLD subjects (30.0% vs 33.7%, respectively,
      P=0.060). NAFLD subjects were at higher odds of OLD (odds ratio=1.334; 95%
      confidence interval=1.108-1.607, P=0.002) than non-NAFLD subjects, after
      adjusting for age, sex, and smoking history. OLD subjects were at higher odds of
      NAFLD (odds ratio=1.556; 95% confidence interval=1.288-1.879, P<0.001) than non
      OLD subjects, after adjusting for age, sex, and smoking history. Conclusion: This
      study showed that NAFLD is related to OLD. Clinicians should be aware of possible
      liver comorbidities in OLD patients and that extrahepatic disease in NAFLD
      patients may vary more than previously thought.

PMID- 30214180
TI  - Daily duration of long-term oxygen therapy and risk of hospitalization in oxygen
      dependent COPD patients.
AB  - Introduction: Long-term oxygen therapy (LTOT) improves survival and may reduce
      hospital admissions in patients with chronic obstructive pulmonary disease (COPD)
      and severe hypoxemia, but the impact of daily duration of LTOT on hospitalization
      rate is unknown. We aimed to estimate the association between the daily duration
      of LTOT (24 vs 15 h/d) and hospital admissions in patients with LTOT due to COPD.
      Materials and methods: A population-based, cohort study included patients who
      started LTOT due to COPD between October 1, 2005 and June 30, 2009 in the Swedish
      national register for respiratory failure (Swedevox). Time to first
      hospitalization from all causes and from respiratory or nonrespiratory disease,
      using the National Patient Registry, was analyzed using Fine-Gray regression,
      adjusting for potential confounders. Results: A total of 2,249 patients with COPD
      (59% women) were included. LTOT 24 h/d was prescribed to 539 (24%) and LTOT 15-16
      h/d to 1,231 (55%) patients. During a median follow-up of 1.1 years
      (interquartile range, 0.6-2.1 years), 1,702 (76%) patients were hospitalized. No
      patient was lost to follow-up. The adjusted rate of all-cause hospitalization was
      similar between LTOT 24 and 15-16 h/d (subdistribution hazard ratio [SHR] 0.96;
      [95% CI] 0.84-1.08), as was cause-specific hospitalizations analyzed for
      respiratory disease (SHR: 1.00; 95% CI: 0.86-1.17) and nonrespiratory disease
      (SHR: 0.92; 95% CI: 0.75-1.14). Conclusion: LTOT prescribed for 24 h/d was not
      associated with decreased hospitalization rates compared with LTOT for 15-16 h/d
      in patients with oxygen-dependent COPD. The results should be validated in a
      randomized controlled trial.

PMID- 30214179
TI  - Vitamin D status is associated with muscle strength and quality of life in
      patients with COPD: a seasonal prospective observation study.
AB  - Background: Owing to hospitalization, reduced functional capacity and
      consequently, less sunlight exposure, suboptimal vitamin D status (25
      hydroxyvitamin D [25(OH)D]?50 nmol/L) is prevalent among COPD patients.
      Objective: This study aimed to investigate seasonal changes in vitamin D status
      and any associated changes in fat-free mass (FFM), muscle strength and quality of
      life (QoL) in COPD patients. Patients and methods: COPD patients living in
      Northern Ireland (n=51) completed study visits at the end of winter (March/April)
      and at the end of summer (September/October), corresponding to the nadir and peak
      of vitamin D status, respectively. At both time points, serum concentration of
      25(OH)D was quantified by liquid chromatography-tandem mass spectrometry, FFM
      (kg) was measured using bioelectrical impedance and muscle strength (kg) was
      measured using handgrip dynamometry. QoL was assessed using the validated St
      George's Respiratory Questionnaire. Results: Mean+/-SD 25(OH)D concentration was
      significantly higher at the end of summer compared to the end of winter (52.5+/
      30.5 nmol/L vs 33.7+/-28.4 nmol/L, P<0.001); and house- bound patients had
      significantly lower 25(OH)D concentration compared to nonhousebound patients at
      the end of summer (42.9+/-4.2 vs 57.2+/-9.9 nmol/L; P?0.001). Muscle strength (at
      both time points) and QoL (end of summer only) were positively predicted by
      25(OH)D concentration, independent of age, sex and smoking status. Conclusion:
      This study highlights the need for health policies to include a recommendation
      for year-round vitamin D supplementation in housebound COPD patients, and
      wintertime supplementation in nonhousebound patients, to maintain optimal 25(OH)D
      concentrations to protect musculoskeletal health. Furthermore, an optimal vitamin
      D status may have potential benefits for QoL in these patients.

PMID- 30214181
TI  - COPD uncovered: a cross-sectional study to assess the socioeconomic burden of
      COPD in Japan.
AB  - Background: COPD remains a major health problem in Japan. Patients with COPD
      experience a reduced quality of life (QoL) and have a higher chance of work
      impairment and productivity loss. However, there is a lack of data on the impact
      of COPD in terms of QoL and work activity impairment in Japan. This study
      assessed the socioeconomic burden of COPD in Japan and the impact it may have on
      the working age population. Patients and methods: This was a 2-year retrospective
      chart review in COPD patients aged >=40 years, with at least one health care
      visit to clinic or hospital in the previous 12 months. Patients were required to
      have available medical charts for at least the previous 24 months. Symptoms were
      assessed using COPD assessment test score; EuroQoL Group 5 Dimension (EQ-5D-5L)
      and work productivity and activity impairment general health questionnaires were
      used to evaluate health-related QoL and work productivity, and health care
      resource utilization data were obtained from clinical charts. Results: In total,
      71 patients aged <65 years, and 151 patients aged >=65 years were included; the
      majority of patients had moderate or severe airflow limitation. Exacerbations
      (moderate or severe) were reported by ~35% of patients in both age groups; 52.1%
      and 62.9% of patients in the <65-year and >=65-year age groups had COPD
      assessment test scores >=10. EQ-5D-5L index scores in the <65-year and >=65-year
      age groups were 0.79 and 0.77, respectively. Work productivity and activity
      impairment scores were higher in <65-year age group. Annual costs of health care
      resource use per patient in the <65-year and >=65-year age groups were Y438,975
      (US$4,389) and Y467,871 (US$4,678), respectively. Costs due to productivity loss
      were estimated to be Y5,287,024 (US$52,870) in the <65-year age group and
      Y3,018,974 (US$30,187) in the >=65-year age group. Conclusion: COPD represents a
      significant socioeconomic burden in Japan. Patients with COPD report significant
      use of health care resources. Higher impact on work impairment and productivity
      loss was observed frequently in the working age population.

PMID- 30214182
TI  - Gene expression profile of human lung in a relatively early stage of COPD with
      emphysema.
AB  - Purpose: As only some smokers develop COPD with emphysema, we explored the
      molecular pathogenesis of early-stage COPD with emphysema using gene expression
      profiling of human lung tissues. Patients and methods: First, 110 subjects who
      had smoked more than ten pack-years were classified into three groups: COPD with
      emphysema, COPD without emphysema, and healthy smokers. COPD and emphysema were
      confirmed by post-bronchodilator forced expiratory volume in 1 second/forced
      vital capacity <0.7 and by chest computed tomography. Lung tissues obtained
      surgically from the 110 subjects were processed and used for RNA-Seq analysis.
      Results: Among the 110 subjects, 29 had COPD with emphysema, 21 had COPD without
      emphysema, and 60 were healthy smokers; their mean post-bronchodilator forced
      expiratory volume in 1 second values were 78%, 80%, and 94%, respectively. Using
      RNA-Seq, we evaluated 16,676 genes expressed in lung tissues. Among them, 1,226
      genes in the COPD with emphysema group and 434 genes in the COPD without
      emphysema group were differentially expressed genes compared to the expression in
      healthy smokers. In the COPD with emphysema group, ACER2 and LMAN2L were markedly
      increased and decreased, respectively. In the COPD without emphysema group, the
      CHRM3 gene, previously reported to be associated with COPD, and HDAC10 were
      markedly increased and decreased, respectively. Conclusion: Our study identified
      differences in gene expression in subjects with COPD according to emphysema
      status using RNA-Seq transcriptome analysis. These findings may have mechanistic
      implications in COPD.

PMID- 30214183
TI  - Effect of tele-health care on quality of life in patients with severe COPD: a
      randomized clinical trial.
AB  - Background and objective: Telemonitoring (TM) of patients with COPD has gained
      much interest, but studies have produced conflicting results. We aimed to
      investigate the effect of TM with the option of video consultations on quality of
      life (QoL) in patients with severe COPD. Patients and methods: COPD patients at
      high risk of exacerbations were eligible for the 6-month study and a total of 281
      patients were equally randomized to either TM (n=141) or usual care (n=140). TM
      comprised recording of symptoms, oxygen saturation, spirometry, and video
      consultations. Algorithms generated alerts if readings breached thresholds. Both
      groups filled in a health-related QoL questionnaire (15D(c)) and the COPD
      Assessment Test (CAT) at baseline and at 6 months. Within-group differences were
      analyzed by paired t-test. Results: Most of the enrolled patients had severe COPD
      (86% with Global Initiative for Chronic Obstructive Lung Disease stage 3 or 4 and
      45% with admission for COPD within the last year, respectively). No difference in
      drop-out rate and mortality was found between the groups, and likewise there was
      no difference in 15D or CAT at baseline. At 6 months, a significant improvement
      of 0.016 in 15D score (p=0.03; minimal clinically important difference 0.015) was
      observed in the TM group (compared to baseline), while there was no improvement
      in the control group -0.003 (p=0.68). After stratifying 15D score at baseline to
      <0.75 or >=0.75, respectively, there was a significant difference in the <0.75 TM
      group of 0.037 (p=0.001), which is a substantial improvement. No statistically
      significant changes were found in CAT score. Conclusion: Compared to the
      nonintervention group, TM as an add-on to usual care over a 6-month period
      improved QoL, as assessed by the 15D questionnaire, in patients with severe COPD,
      whereas no difference between groups was observed in CAT score.

PMID- 30214184
TI  - Oropharyngeal swallow physiology and swallowing-related quality of life in
      underweight patients with concomitant advanced chronic obstructive pulmonary
      disease.
AB  - Background: Swallowing impairment (dysphagia) has been associated with COPD and
      may contribute to exacerbations of this chronic and progressive disease. Further,
      risk of mortality increases with concomitant presence of cachexia in the COPD
      population. The purpose of this prospective study was to depict oropharyngeal
      swallowing physiology in underweight patients with stable but advanced-stage
      COPD. Patients and methods: Ten underweight patients with stable but advanced
      COPD underwent a modified barium swallow study. Analysis of oropharyngeal
      swallowing function was completed using the standardized Modified Barium Swallow
      Impairment Profile and the Penetration-Aspiration Scale. Scores from the
      Dysphagia Handicap Index and 10-item Eating Assessment Tool were collected to
      assess patient perception of swallowing difficulty. Findings were compared to age
      and sex-matched healthy controls. Results: Significantly higher MBSImP oral
      total scores (P=0.007) were observed in COPD patients compared to matched
      controls, but no difference was observed in pharyngeal total scores (P=0.105).
      Patients with COPD had significantly higher maximum PAS scores compared with
      controls (P=0.030). There was no significant difference in EAT-10 or DHI scores
      between patients with COPD and controls (P=0.41 and P=0.08, respectively).
      Conclusion: Underweight patients with severe but stable COPD present with
      dysphagia that may not be recognized by the patient. Further investigation is
      needed to elucidate the interaction between the respiratory-swallowing systems,
      how muscular weakness may contribute to swallowing impairment, and responsiveness
      to swallowing treatment.

PMID- 30214185
TI  - A randomized study using functional respiratory imaging to characterize
      bronchodilator effects of glycopyrrolate/formoterol fumarate delivered by a
      metered dose inhaler using co-suspension delivery technology in patients with
      COPD.
AB  - Background: Functional respiratory imaging (FRI) uses high-resolution computed
      tomography (HRCT) scans to assess changes in airway volume and resistance.
      Patients and methods: In this randomized, double-blind, 2-week, crossover, Phase
      IIIB study, patients with moderate-to-severe COPD received twice-daily
      glycopyrrolate/formoterol fumarate delivered by a metered dose inhaler (GFF MDI,
      18/9.6 MUg) and placebo MDI, formulated using innovative co-suspension delivery
      technology. Co-primary endpoints included the following: specific image-based
      airway volume (siVaw) and specific image-based airway resistance (siRaw) at Day
      15, measured using FRI. Secondary and other endpoints included the following:
      change from baseline in post-dose forced expiratory volume in 1 second (FEV1) and
      inspiratory capacity (IC; spirometry) and ratio to baseline in post-dose
      functional residual capacity (FRC) and residual volume (RV; body
      plethysmography). Results: Twenty patients (46-78 years of age) were randomized
      and treated; of whom 19 completed the study. GFF MDI treatment increased siVaw by
      75% and reduced siRaw by 71% vs placebo MDI (both P<0.0001). Image-based airway
      volume (iVaw) and image-based airway resistance (iRaw), without adjusting for
      lobe volume, demonstrated corresponding findings to the co-primary endpoint, as
      lobe volumes did not change with either treatment. Approximately 48% of the
      delivered dose of glycopyrronium and formoterol fumarate was estimated to be
      deposited in the lungs. Compared with placebo, GFF MDI treatment improved post
      dose FEV1 and IC (443 mL and 454 mL, respectively; both P<0.001) and reduced FRC
      and RV (13% and 22%, respectively; both P<0.0001). There were no significant
      safety findings. Conclusion: GFF MDI demonstrated significant, clinically
      meaningful benefits on FRI-based airway volume and resistance in patients with
      moderate-to-severe COPD. Benefits were associated with improvements in FEV1, IC,
      and hyperinflation. Clinical trial registration: ClinicalTrials.gov: NCT02643082.

PMID- 30214186
TI  - Determining the minimally important difference in quadriceps strength in
      individuals with COPD using a fixed dynamometer.
AB  - Background: Measurement of quadriceps muscular force is recommended in
      individuals with COPD, notably during a pulmonary rehabilitation program (PRP).
      However, the tools used to measure quadriceps maximal voluntary contraction
      (QMVC) and the clinical relevance of the results, as well as their interpretation
      for a given patient, remain a matter of debate. The objective of this study was
      to estimate the minimally important difference (MID) of QMVC using a fixed
      dynamometer in individuals with COPD undergoing a PRP. Methods: Individuals with
      COPD undergoing a PRP were included in this study. QMVC was measured using a
      dynamometer (MicroFET2) fixed on a rigid support according to a standard-ized
      methodology. Exercise capacity was measured by 6-minute walk distance (6MWD) and
      evaluation of quality of life with St George's respiratory questionnaire (SGRQ)
      and Hospital Anxiety and Depression Scale (HADS) total scores. All measures were
      obtained at baseline and the end of the PRP. The MID was calculated using
      distribution-based methods. Results: A total of 157 individuals with COPD (age
      62.9+/-9.0 years, forced expiratory volume in 1 second 47.3%+/-18.6% predicted)
      were included in this study. At the end of the PRP, the patients had improved
      their quadriceps force significantly by 8.9+/-15.6 Nm (P<0.001), as well as 6MWD
      by 42+/-50 m (P<0.001), SGRQ total score by -9+/-17 (P<0.001) and HADS total
      score by -3+/-6 (P<0.001). MID estimation using distribution-based analysis was
      7.5 Nm by empirical rule effect size and 7.8 Nm by Cohen's effect size.
      Conclusion: Measurement of QMVC using a fixed dynamometer is a simple and
      valuable tool capable of assessing improvement in quadriceps muscle force after a
      PRP. We suggest an MID of 7.5 Nm to identify beneficial changes after a PRP
      intervention.

PMID- 30214187
TI  - Exhaled nitric oxide in patients with chronic obstructive pulmonary disease: a
      systematic review and meta-analysis.
AB  - Background: Fractional exhaled nitric oxide (FENO) is a useful and noninvasive
      biomarker for eosinophilic airway inflammation, particularly in asthma. However,
      its utility in chronic obstructive pulmonary disease (COPD) remains
      controversial. In this study, we performed a systematic review and meta-analysis
      to evaluate FENO levels in COPD. Methods: A search of PubMed, Embase, Cochrane
      Library, and clinical trial registry was conducted from inception to January
      2018. Studies were included if they reported FENO levels in patients with COPD
      and healthy controls. We then extracted relevant information and analyzed data.
      Standard mean difference (SMD) with 95% confidence interval (CI) was applied in
      this meta-analysis. Results: A total of 2,073 studies were reviewed for
      eligibility, with 24 studies pooled for analysis. The FENO levels in patients
      with COPD were elevated mildly compared with healthy controls (SMD 1.28, 95% CI
      0.60-1.96). A similar result was also observed in stable COPD, with an SMD of
      1.21 (95% CI 0.47-1.96). On the other hand, we found no association between FENO
      levels and exacerbated COPD. Additionally, for patients with COPD, ex-smokers had
      higher levels of FENO than current smokers (SMD 2.05, 95% CI 1.13-2.97).
      Conclusion: Our studies demonstrated a mild elevation of FENO in COPD, and the
      association between exacerbated COPD and FENO levels needs to be further
      explored. The potential mechanism is still unknown and conflicting.

PMID- 30214188
TI  - Cost-effectiveness of roflumilast as an add-on to triple inhaled therapy vs
      triple inhaled therapy in patients with severe and very severe COPD associated
      with chronic bronchitis in the UK.
AB  - Purpose: Patients with severe COPD are at high risk of experiencing disease
      exacerbations, which require additional treatment and are associated with
      elevated mortality and increased risk of future exacerbations. Some patients
      continue to experience exacerbations despite receiving triple inhaled therapy
      (ICS plus LAMA plus LABA). Roflumilast is recommended by the Global Initiative
      for Chronic Obstructive Lung Disease as add-on treatment to triple inhaled
      therapy for these patients. This cost-effectiveness analysis compared costs and
      quality-adjusted life-years for roflumilast plus triple inhaled therapy vs triple
      inhaled therapy alone, using data from the REACT and RE2SPOND trials. Patients
      and methods: Patients included in the analysis had severe to very severe COPD,
      FEV1 <50% predicted, symptoms of chronic bronchitis and >=2 exacerbations per
      year. Our model was adapted from a previously published and validated model, and
      the analyses conducted from a UK National Health Service perspective. A scenario
      analysis considered a subset of patients who had experienced at least one COPD
      related hospitalization within the previous year. Results: Roflumilast as add-on
      to triple inhaled therapy was associated with non-significant reductions in rates
      of both moderate and severe exacerbations compared with triple inhaled therapy
      alone. The incremental cost-effectiveness ratio (ICER) for roflumilast as add-on
      to triple inhaled therapy was L24,976. In patients who had experienced previous
      hospitalization, roflumilast was associated with a non-significant reduction in
      the rate of moderate exacerbations, and a statistically significant reduction in
      the rate of severe exacerbations. The ICER for roflumilast in this population was
      L7,087. Conclusions: Roflumilast is a cost-effective treatment option for
      patients with severe or very severe COPD, chronic bronchitis, and a history of
      exacerbations. The availability of roflumilast as add-on treatment addresses an
      important unmet need in this patient population.

PMID- 30214189
TI  - Delivery siRNA with a novel gene vector for glioma therapy by targeting Gli1.
AB  - Background: Gene therapy has recently shown considerable clinical benefit in
      cancer therapy during the past few years, and the application of this choice in
      cancer treatments is increasing continually. Gli1 is an ideal candidate target
      for cancer gene therapy and is important for tumorigenesis. Methods: In this
      study, we developed a novel gene delivery system with a self-assembly method by
      using a 1,2-dioleoyl-3-trimethylammonium-propane and methoxy poly (ethylene
      glycol)-poly(lactide) copolymer (DMP), with zeta potential of 32.7 mV and
      measuring 35.6 nm. The effect of this delivery system was tested in vitro and in
      vivo. Results: DMP showed good performance in delivering siRNA to glioma cells in
      vitro with high transfection performance (98%). Moreover, DMP-Gli1si shows a
      satisfactory anti-glioma effect via induction of cell apoptosis and cell growth
      inhibition in vitro. Furthermore, for subcutaneous tumor-bearing mice, treatment
      with the DMP-Gli1si complex significantly inhibited tumor growth by inhibiting
      Gli1 protein expression, promoting apoptosis, and reducing proliferation.
      Conclusion: The complex of Gli1 siRNA and DMP may potentially play an important
      role as a new drug in the clinical treatment of gliomas.

PMID- 30214190
TI  - Tumor-specific delivery of therapeutic siRNAs by anti-EGFR immunonanoparticles.
AB  - Background: Efficient target-specific siRNA delivery has always been a primary
      concern in the field of siRNA clinical application. Purpose: In this study, four
      different types of anti-epidermal growth factor receptor (EGFR) antibody
      conjugated immunonanoparticles were prepared and tested for cancer cell-targeted
      therapeutic siRNA delivery. Materials and methods: The prepared nanoparticles
      encapsulating siRNAs were character-ized by gel retardation and particle analysis
      using a Zetasizer. In vitro transfection and reduction of target genes, vimentin
      and JAK3, were determined using quantitative reverse transcription polymerase
      chain reaction. In vivo tumor targeting and antitumoral efficacies of the
      nanoparticles were evaluated in mice carrying tumors. Results: Among these
      immunonanoparticles, anti-EGFR immunolipoplexes and immunoviroplexes exhibited
      remarkable cell binding and siRNA delivery to EGFR-expressing tumor cells
      compared to immunoliposomes and immunovirosomes. Especially, the anti-EGFR
      immunoviroplexes exhibited the most efficient siRNA transfection to target tumor
      cells. Therefore, antitumoral vimentin and Janus kinase-3 siRNAs were loaded in
      the anti-EGFR immunolipoplexes and immunoviroplexes, which were tested in mice
      carrying SK-OV-3 tumor xenografts. In fact, the therapeutic siRNAs were
      efficiently delivered to the tumor tissues by both delivery vehicles, resulting
      in significant inhibition of tumor growth. Moreover, administration of
      doxorubicin in combination with anti-EGFR immunoviroplexes resulted in remarkable
      and synergistic tumor growth inhibition. Conclusion: This study provides
      experimental proof that cancer cell-targeted immunoviroplexes are an efficient
      siRNA delivery system for cancer therapy. Moreover, this study also suggests that
      a combination of conventional chemotherapy and tumor-directed anticancer siRNA
      therapy would be a better modality for cancer treatment.

PMID- 30214191
TI  - Icariin-loaded electrospun PCL/gelatin sub-microfiber mat for preventing epidural
      adhesions after laminectomy.
AB  - Background: Epidural adhesion is one of the major reasons attributed to failed
      back surgery syndrome after a successful laminectomy, and results in serious
      clinical complications which require management from physicians. Therefore, there
      is an urgent demand within the field to develop biodegradable anti-adhesion
      membranes for the prevention of post-operative adhesion. Methods: In this study,
      icariin (ICA) was initially loaded into polycaprolactone (PCL)/gelatin fibers via
      electrospinning to fabricate nanofibrous membranes. The effects of the ICA
      content (0.5wt%, 2wt% and 5wt%) and the bioactivity of ICA in the nanofibrous
      membranes were investigated in vitro and in vivo. Results: The nanofibrous
      membranes showed suitable pore size and good properties that were unaffected by
      ICA concentration. Moreover, the ICA-loaded membranes exhibited an originally
      rapid and subsequently gradual sustained ICA release profile that could
      significantly prevent fibroblast adhesion and proliferation. In vivo studies with
      rabbit laminectomy models demonstrated that the ICA-loaded membranes effectively
      reduced epidural adhesion by gross observation, histology, and biochemical
      evaluation. The anti-adhesion mechanism of ICA was found to be via suppression of
      the TGF-beta/Smad signaling proteins and down regulation of collage I/III and a
      SMA expression for the first time. Conclusion: We believe that these ICA-loaded
      PCL/gelatin electrospun membranes provide a novel and promising strategy to
      resist adhesion formation following laminectomy in a clinical application.

PMID- 30214192
TI  - Erratum: Treatment of a multiple sclerosis animal model by a novel nanodrop
      formulation of a natural antioxidant [Corrigendum].
AB  - [This corrects the article on p. 7165 in vol. 10, PMID: 26648720.].

PMID- 30214193
TI  - Anticancer activity of paclitaxel-loaded keratin nanoparticles in two-dimensional
      and perfused three-dimensional breast cancer models.
AB  - Purpose: Taxanes are highly effective cytotoxic drugs for progressing breast
      cancer treatment. However, their poor solubility and high toxicity urge the
      development of innovative formulations of potential clinical relevance. Materials
      and methods: By using a simple and straightforward aggregation method, we have
      generated paclitaxel (PTX) loaded in keratin nanoparticles (KER-NPs-PTX). Their
      activities were tested against human breast cancer MCF-7 and MDA MB 231 cell
      lines in conventional two-dimensional (2D) cultures and in a dynamic three
      dimensional (3D) model with perfused bioreactor (p3D). Moreover, KER-NPs-PTX
      activity was compared to free PTX and to PTX loaded in albumin nanoparticles (HSA
      NPs-PTX). Cell viability, induction of apoptosis, and gene expression analysis
      were used as readouts. Results: In 2D cultures, KER-NPs-PTX was able to inhibit
      tumor cell viability and to induce apoptosis similarly to PTX and HSA-NPs-PTX. In
      the p3D model, a lower sensitivity of tumor cells to treatments was observed.
      Importantly, only KER-NPs-PTX was able to induce a statistically significant
      increase in apoptotic cell percentages following 24 h treatment for MCF-7 (16.7+/
      4.0 early and 11.3+/-4.9 late apoptotic cells) and 48 h treatment for MDA MB 231
      (21.3+/-11.2 early and 10.5+/-1.8 late apoptotic cells) cells. These effects were
      supported, at least for MCF-7 cells, by significant increases in the expression
      of proapoptotic BAX gene (5.8+/-0.5) 24 h after treatment and of cleaved caspase
      3 (CC3) protein. Conclusion: KER-NPs-PTX, generated by a simple procedure, is
      characterized by high water solubility and enhanced PTX-loading ability, as
      compared to HSA-NPs-PTX. Most importantly, it appears to be able to exert
      effective anticancer activities on breast cancer cells cultured in 2D or in p3D
      models.

PMID- 30214194
TI  - Antitumor effect of gemcitabine-loaded albumin nanoparticle on gemcitabine
      resistant pancreatic cancer induced by low hENT1 expression.
AB  - Purpose: Gemcitabine is currently the standard first-line chemotherapeutic drug
      for treating pancreatic cancer. However, many factors can contribute to
      gemcitabine resistance. One of the most important reasons is the low hENT1
      expression. In this study, we tested the antitumor effect of gemcitabine-loaded
      human serum albumin nanoparticle (GEM-HSA-NP) on gemcitabine-resistant pancreatic
      cancer induced by low hENT1 expression. Materials and methods: S-(4-nitrobenzyl)
      6-thioinosine was utilized to inhibit the activity of hENT1 and simulate low
      hENT1 expression. Growth inhibition assays and cell cycle and apoptosis analyses
      were performed on human pancreatic cancer cell lines such as BxPC-3 and SW1990.
      The in vivo antitumor effect was studied by using patient-derived xenograft (PDX)
      models. The in vivo toxicity assessment was performed on healthy Kunming mice.
      Results: In in vitro studies, GEM-HSA-NP showed its ability to inhibit cell
      proliferation, arrest cell cycle and induce apoptosis when tumor cells were
      resistant to gemcitabine. In in vivo studies, GEM-HSA-NP was more effective than
      gemcitabine on inhibiting tumor growth whether the expression levels of hENT1
      were high or low in PDX models. The in vivo toxicity assessment showed that the
      biotoxicity of GEM-HSA-NP did not increase compared with gemcitabine. Conclusion:
      GEM-HSA-NP can overcome gemcitabine resistance induced by low hENT1 expression,
      which suggests its potential role for the clinical application.

PMID- 30214195
TI  - Low-molecular-weight sulfonated chitosan as template for anticoagulant
      nanoparticles.
AB  - Purpose: In this work, low-molecular-weight sulfoethyl chitosan (SECS) was used
      as a model template for the generation of silver core-shell nanoparticles with
      high potential as anticoagulants for medical applications. Materials and methods:
      SECS were synthesized by two reaction pathways, namely Michael addition and a
      nucleophilic substitution with sodium vinylsulfonate or sodium 2
      bromoethanesulfonate (NaBES). Subsequently, these derivatives were used as
      reducing and capping agents for silver nanoparticles in a microwave-assisted
      reaction. The formed silver-chitosan core-shell particles were further surveyed
      in terms of their anticoagulant action by different coagulation assays focusing
      on the inhibition of either thrombin or cofactor Xa. Results: In-depth
      characterization revealed a sulfoalkylation of chitosan mainly on its sterically
      favored O6-position. Moreover, comparably high average degrees of substitution
      with sulfoethyl groups (DSSE) of up to 1.05 were realized in reactions with
      NaBES. The harsh reaction conditions led to significant chain degradation and
      consequently, SECS exhibits masses of <50 kDa. Throughout the following microwave
      reaction, stable nanoparticles were obtained only from highly substituted
      products because they provide a sufficient charge density that prevented
      particles from aggregation. High-resolution transmission electron microscopy
      images reveal that the silver core (diameter ~8 nm) is surrounded by a 1-2 nm
      thick SECS layer. These core-shell particles and the SECS itself exhibit an
      inhibiting activity, especially on cofactor Xa. Conclusion: This interesting
      model system enabled the investigation of structure-property correlations in the
      course of nanoparticle formation and anticoagulant activity of SECS and may lead
      to completely new anticoagulants on the basis of chitosan-capped nanoparticles.

PMID- 30214196
TI  - Macropinocytosis activated by oncogenic Dbl enables specific targeted delivery of
      Tat/pDNA nano-complexes into ovarian cancer cells.
AB  - Background: Successful implementation of gene therapy heavily relies on
      efficiently delivering genetic materials and specific targeting into cells.
      Oncogene-driven endocytosis stimulates nutrient uptake and also develops an
      endocytosis-mediated defense against therapeutic agents. Cell-penetrating
      peptides, typically HIV-Tat, are well known for efficient delivery of nucleic
      acid drugs but lack targeting specificity. Various passive targeting strategies
      were pursued to enhance the tumor targeting efficiency; however, they are still
      limited by complicated cellular endocytosis routes and the heterogeneity of
      cancer types. Methods: Tat/pDNA complexes were noncovalently compacted and their
      physiochemical properties were determined. The siRNA pool and pLV-RNAi-GFP
      lentivirus were used to knock down dbl oncogene (originally isolated from diffuse
      B-cell lymphoma) expression, and its overexpression was performed by plasmid
      transient transfection. The cellular uptake of fluorescent ligands was quantified
      by confocal imaging and flow cytometry analysis. The transgene efficiency was
      determined by the Luciferase expression assay. Rho GTPase activation was checked
      by the GST-Rho GTPase-binding domain pull-down assay. Results: pGL3 plasmid DNA
      was noncovalently compacted with the Tat peptide into nano-size complexes at high
      N/P ratios. Macropinocytosis, a clathrin- and caveolin-independent endocytosis
      process, was shown to contribute to the uptake of middle-sized (~600 nm) Tat/pGL3
      complexes. Cell-type-specific variation in macropinocytosis was essentially
      controlled by the action of the Dbl oncogene. Onco-Dbl presentation constantly
      induced a high level of macropinocytosis activity in ovarian cancer cells. Onco
      Dbl overexpression hyperstimulated macropinocytosis enhancement in cells mainly
      through actin cytoskeleton reorganization mediated by the PH domain and Rac1
      activation. The Dbl-driven Rho GTPase signaling collectively determined the cell
      type-specific macropinocytosis phenotype. Conclusion: Such an aspect can be
      exploited to selectively confer targeted delivery of Tat/pDNA nano-complexes into
      ovarian cancer cells. Our work provides a novel alternative for targeted delivery
      of cell-penetrating peptide-based nucleic acid drugs into certain tumor types if
      specific endocytosis pathways are used.

PMID- 30214197
TI  - Studies of acute and subchronic systemic toxicity associated with a copper/low
      density polyethylene nanocomposite intrauterine device.
AB  - Introduction: The physiologic safety of devices and materials intended for
      clinical implantation should be evaluated. This study, a logical extension of our
      previous work, aimed to investigate the safety of a novel contraceptive device,
      the copper/low-density polyethylene nanocomposite intrauterine device (nano
      Cu/LDPE IUD), through studies of its potential toxicity after acute and
      subchronic administration in mice and rats. Methods: For the acute toxicity
      study, single 50 mL/kg doses of nano-Cu/LDPE IUD extracts were administered to
      mice via intravenous or intraperitoneal injection. General behavioral adverse
      effects, mortality, and body weights were evaluated for up to 72 hours. In the 13
      week subchronic toxicity study, the nano-Cu/LDPE composite with 10-fold higher
      than the standard clinical dose was implanted subcutaneously into the dorsal skin
      of Wistar rats. The control group underwent a sham procedure without material
      insertion. Results: During all acute study observation times, the biologic
      reactions of the mice in the nano-Cu/LDPE group did not differ from those
      observed in the control group. The groups did not differ statistically in terms
      of body weight gain, and no macroscopic changes were observed in any organs. In
      the subchronic study, no clinical signs of toxicity or mortality were observed in
      either the nano-Cu/LDPE or control group during the 13-week period. The nano
      Cu/LDPE composite did not cause any alterations in body weight, food consumption,
      hematologic and biochemical parameters, or organ weight relative to the control
      for any observed sample group. Histopathologic examinations of the organs
      revealed normal architecture, indicating that the inserted material did not cause
      morphologic disturbances in the rats. Conclusion: Overall, the results indicate
      that the nano-Cu/LDPE IUD did not induce systemic toxicity under experimental
      conditions of the recommended standard practices, suggesting that the novel
      material IUD is safe and feasible for future contraceptive applications.

PMID- 30214198
TI  - Mangosteen pericarp extract embedded in electrospun PVP nanofiber mats:
      physicochemical properties and release mechanism of alpha-mangostin.
AB  - Background: alpha-Mangostin is a major active compound of mangosteen (Garcinia
      mangostana L.) pericarp extract (MPE) that has potent antioxidant activity.
      Unfortunately, its poor aqueous solubility limits its therapeutic application.
      Purpose: This paper reports a promising approach to improve the clinical use of
      this substance through electrospinning technique. Methods: Polyvinylpyrrolidone
      (PVP) was explored as a hydrophilic matrix to carry alpha-mangostin in MPE.
      Physicochemical properties of MPE:PVP nanofibers with various extract-to-polymer
      ratios were studied, including morphology, size, crystallinity, chemical
      interaction, and thermal behavior. Antioxidant activity and the release of alpha
      mangostin, as the chemical marker of MPE, from the resulting fibers were
      investigated. Results: It was obtained that the MPE:PVP nanofiber mats were flat,
      bead-free, and in a size range of 387-586 nm. Peak shifts in Fourier-transform
      infrared spectra of PVP in the presence of MPE suggested hydrogen bond formation
      between MPE and PVP. The differential scanning calorimetric study revealed a
      noticeable endothermic event at 119 degrees C in MPE:PVP nanofibers, indicating
      vaporization of moisture residue. This confirmed hygroscopic property of PVP. The
      absence of crystalline peaks of MPE at 2theta of 5.99 degrees , 11.62 degrees ,
      and 13.01 degrees  in the X-ray diffraction patterns of electrospun MPE:PVP
      nanofibers showed amorphization of MPE by PVP after being electrospun. The
      radical scavenging activity of MPE:PVP nanofibers exhibited lower IC50 value (55
      67 ug/mL) in comparison with pure MPE (69 ug/mL). The PVP:MPE nanofibers
      tremendously increased the antioxidant activity of alpha-mangostin as well as its
      release rate. Applying high voltage in electrospinning process did not destroy
      the chemical structure of alpha-mangostin as indicated by retained in vitro
      antioxidant activity. The release rate of alpha-mangostin significantly increased
      from 35% to over 90% in 60 minutes. The release of alpha-mangostin from MPE:PVP
      nanofibers was dependent on alpha-mangostin concentration and particle size, as
      confirmed by the first-order kinetic model as well as the Hixson-Crowell kinetic
      model. Conclusion: We successfully synthesized MPE:PVP nanofiber mats with
      enhanced antioxidant activity and release rate, which can potentially improve the
      therapeutic effects offered by MPE.

PMID- 30214199
TI  - Layer-by-layer DNA films incorporating highly transfecting bioreducible
      poly(amido amine) and polyethylenimine for sequential gene delivery.
AB  - Background: The layer-by-layer (LbL) assembly method offers a molecular level
      control of the amount and spatial distribution of bioactive molecules. However,
      successful clinical translation of LbL film technology will most certainly
      require a better understanding and control of not only the film assembly process,
      but also film disassembly kinetics in physiologic conditions. Purpose: This work
      focuses on the understanding and control of degradation properties of LbL films
      for localized gene delivery. Methods: Bioreducible poly(amido amine)s (PAAs)
      containing cystaminebisacrylamide (CBA), methylenebisacrylamide, and 5-amino-1
      pentanol (APOL) were synthesized by Michael addition polymerization for the
      construction of bioreducible LbL films capable of sequential gene delivery.
      Results: The synthesized PAAs were screened for desirable buffering capacity,
      cell transfection, and cytotoxicity characteristics together with 25 kDa branched
      polyethylenimine (PEI) and cross-linked 800 Da PEI. By screening the various
      polycations we were able to identify a copolymer of CBA and APOL for the
      subsequent construction of the LbL films. By incorporating a highly transfecting
      polycation and a nondiffusing polycation we were able to improve the overall
      transfection of HEK293 and MC3T3 cells from the bioreducible LbL films. We also
      demonstrated the dual-stage release and transfection of two different DNAs from
      the LbL films. Conclusion: The results indicate that LbL films consisting of
      bioreducible PAAs and non-diffusing polyelectrolytes have excellent degradation
      properties for the development of LbL coating technology for localized gene
      delivery applications.

PMID- 30214201
TI  - Surface-enhanced Raman spectroscopy of blood serum based on gold nanoparticles
      for tumor stages detection and histologic grades classification of oral squamous
      cell carcinoma.
AB  - Background: Tumor stages detection and histologic grades classification are
      essential for the diagnosis and prognosis of oral squamous cell carcinoma (OSCC).
      In this research, we apply surface-enhanced Raman spectroscopy (SERS) of blood
      serum to detect the tumor stages and histologic classification of OSCC. Methods:
      According to TNM classification and World Health Organization histologic grading
      system, the blood serum samples were collected from a total of 135 OSCC patients
      in the different tumor stages and histologic grades. Then the SERS spectra of
      serum samples from OSCC patients were diagnosed and classified into different
      groups using principal component analysis (PCA) and linear discriminant analysis
      (LDA) based on the tumor sizes, lymph node metastasis and histologic grades.
      Results: The SERS spectra of blood serum samples have shown the distinct changes
      and differences compared with each other, which were assigned to the biomolecule
      alterations (nucleic acids, proteins, lipids, and so on) in blood serums. And all
      accuracies of detection and classification reached above 85%. Conclusion: This
      study demonstrated that the SERS based on blood serum test had an enormous
      potential to carry out the preoperative assessment and prediction of the OSCC
      patients in different tumor stages and histologic classification.

PMID- 30214200
TI  - Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with
      gambogic acid to enhance targeting and antitumor ability in colorectal cancer
      treatment.
AB  - Background: Red blood cell membrane-coated nanoparticle (RBCm-NP) platform, which
      consist of natural RBCm and synthetic polymeric core, can extend circulation time
      in vivo with an improved biocompatibility and stability of this biomimetic
      nanocarrier. To achieve better bioavailability of antitumor drugs that were
      loaded in RBCm-NPs, the functionalization of coated RBCm with specific targeting
      ability is essential. Bispecific recombinant protein anti-EGFR-iRGD, containing
      both tumor penetrating peptide (internalizing RGD peptide) and EGFR single-domain
      antibody (sdAb), seems to be an optimal targeting ligand for RBCm-NPs in the
      treatment of multiple tumors, especially colorectal cancer with high EGFR
      expression. Materials and methods: We modified the anti-EGFR-iRGD recombinant
      protein on the surface of RBCm-NPs by lipid insertion method to construct iE-RBCm
      PLGA NPs and confirmed the presentation of active tumor-targeting ability in
      colorectal cancer models with high EGFR expression when compared with RBCm-PLGA
      NPs. In addition, potential anti-tumor drug gambogic acid (GA) was loaded into
      the NPs to endow the antitumor efficiency of iE-RBCm-GA/PLGA NPs. It was
      simultaneously evaluated whether GA can reach better biocompatibility benefiting
      from the improved antitumor efficiency of iE-RBCm-GA/PLGA NPs in colorectal
      cancer models. Results: We successfully modified anti-EGFR-iRGD proteins on the
      surface of biomimetic NPs with integrated and stable "shell-core" structure. iE
      RBCm-PLGA NPs showed its improved targeting ability in vitro (multicellular
      spheroids [MCS]) and in vivo (nude mice bearing tumors). Besides, no matter on
      short-term cell apoptosis at tumor site (terminal deoxyribonucleotidyl
      transferase-mediated dUTP nick end labeling [TUNEL]) and long-term tumor
      inhibition, iE-RBCm-GA/PLGA NPs achieved better antitumor efficacy than free GA
      in spite of the similar effects of cytotoxicity and apoptosis to GA in vitro.
      Conclusion: We expect that the bispecific biomimetic nanocarrier can extend the
      clinical application of many other potential antitumor drugs similar to GA and
      become a novel drug carrier in the colorectal cancer treatment.

PMID- 30214202
TI  - Chitosan-polyvinyl alcohol nanoscale liquid film-forming system facilitates MRSA
      infected wound healing by enhancing antibacterial and antibiofilm properties.
AB  - Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the
      most predominant and fatal pathogens at wound infection sites. MRSA is difficult
      to treat because of its antibiotic resistance and ability to form biofilms at the
      wound site. Methods: In this study, a novel nanoscale liquid film-forming system
      (LFFS) loaded with benzalkonium bromide was produced based on polyvinyl alcohol
      and chitosan. Results: This LFFS showed a faster and more potent effect against
      MRSA252 than benzalkonium bromide aqueous solution both in vitro and in vivo.
      Additionally, the LFFS had a stronger ability to destroy biofilms (5 mg/mL) and
      inhibit their formation (1.33 MUg/mL). The LFFS inflicted obvious damage to the
      structure and integrity of MRSA cell membranes and caused increases in the
      release of alkaline phosphate and lactate dehydrogenase in the relative
      electrical conductivity and in K+ and Mg2+ concentrations due to changes in the
      MRSA cell membrane permeability. Conclusion: The novel LFFS is promising as an
      effective system for disinfectant delivery and for application in the treatment
      of MRSA wound infections.

PMID- 30214203
TI  - Amphiphilic peptides as novel nanomaterials: design, self-assembly and
      application.
AB  - Designer self-assembling peptides are a category of emerging nanobiomaterials
      which have been widely investigated in the past decades. In this field,
      amphiphilic peptides have received special attention for their simplicity in
      design and versatility in application. This review focuses on recent progress in
      designer amphiphilic peptides, trying to give a comprehensive overview about this
      special type of self-assembling peptides. By exploring published studies on
      several typical types of amphiphilic peptides in recent years, herein we discuss
      in detail the basic design, self-assembling behaviors and the mechanism of
      amphiphilic peptides, as well as how their nanostructures are affected by the
      peptide characteristics or environmental parameters. The applications of these
      peptides as potential nanomaterials for nanomedicine and nanotechnology are also
      summarized.

PMID- 30214205
TI  - Effects of behavioral activation program without psychotropic medication
      treatment for depression in late adolescence: case report.
AB  - Background: A Japanese study revealed that 20.7% of first-year undergraduate
      students had a major depressive episode during the previous 12 months: first-year
      undergraduate students with depression need early support. Reportedly,
      antidepressant medication use during adolescence is associated with modestly
      increased risk of suicidality. This case study of a late-adolescent woman with
      depression illustrates the effects of behavioral activation without psychotropic
      medication. Case presentation: A first-year undergraduate student was diagnosed
      as having major depressive disorder. From earlier studies, we developed a
      behavioral activation program for late-adolescent people with major depressive
      disorder. Behavioral activation administered in 10 weekly 60-minute sessions
      decreased depressive symptoms, avoidant behaviors, and rumination. Moreover, the
      Beck Depression Inventory, second version score was 1 at 1-year follow-up.
      Conclusion: Results of this case study show that behavioral activation is
      effective without psychotropic medication. Future studies of large samples must
      be conducted to assess the effectiveness of behavioral activation without
      psychotropic medication for depression in late adolescence.

PMID- 30214204
TI  - Natural product-based nanomedicines for wound healing purposes: therapeutic
      targets and drug delivery systems.
AB  - Wound healing process is an intricate sequence of well-orchestrated biochemical
      and cellular phenomena to restore the integrity of the skin and subcutaneous
      tissue. Several plant extracts and their phytoconstituents are known as a
      promising alternative for wound healing agents due to the presence of diverse
      active components, ease of access, and their limited side effects. The
      development of nanotechnological methods can help to improve the efficacy of
      different therapeutics as well as herbal-based products. Here, we present a
      review of the efficacy of the plant based-nanomaterials in the management of
      wounds and discuss the involved therapeutic targets. For this purpose, a profound
      search has been conducted on in vitro, in vivo, and/or clinical evidences
      evaluating the efficacy and pharmacological mechanisms of natural product-based
      nanostructures on different types of wounds. Different pharmacological targets
      are involved in the wound healing effects of herbal-based nanostructures,
      including suppressing the production of inflammatory cytokines and inflammatory
      transduction cascades, reducing oxidative factors and enhancing antioxidative
      enzymes, and promoting neovascularization and angiogenic pathways through
      increasing the expression of vascular endothelial growth factor, fibroblast
      growth factor, and platelet-derived growth factor. Moreover, nanostructure of
      plant extracts and their phytochemicals can enhance their bioavailability,
      control their release in the form of sustained delivery systems to the wound
      site, and enhance the permeability of these therapeutics to the underlying skin
      layers, which are all necessary for the healing process. Overall, various plant
      extracts and their natural compounds, used in nanoformulations, have demonstrated
      high activity in the management of wounds and thus can be assumed as future
      pharmaceutical drugs.

PMID- 30214206
TI  - EEG correlates of induced anxiety in obsessive-compulsive patients: comparison of
      autobiographical and general anxiety scenarios.
AB  - Background: The underlying symptomatology of obsessive-compulsive disorder (OCD)
      can be viewed as an impairment in both cognitive and behavioral inhibition,
      regarding difficult inhibition of obsessions and behavioral compulsions.
      Converging results from neuroimaging and electroencephalographic (EEG) studies
      have identified changes in activities throughout the medial frontal and orbital
      cortex and subcortical structures supporting the cortico-striato-thalamo-cortical
      circuit model of OCD. This study aimed to elucidate the electrophysiological
      changes induced by autobiographical and general anxiety scenarios in patients
      with OCD. Methods: Resting-state eyes-closed EEG data were recorded in 19 OCD
      patients and 15 healthy controls. Cortical EEG sources were estimated by
      standardized low-resolution electromagnetic tomography (sLORETA). The changes in
      the emotional state were induced by two different scenarios: the autobiographical
      script related to patient's OCD symptoms and the script triggering general
      anxiety. Results: During the resting state, we proved increased delta activity in
      the frontal, limbic and temporal lobe and the sub-lobar area in OCD patients. In
      a comparison of neural activities during general anxiety in OCD patients and the
      control group, we proved an increase in delta (parietal, temporal, occipital,
      frontal and limbic lobes, and sub-lobal area), theta (temporal, parietal and
      occipital lobes) and alpha-1 activities (parietal lobe). Finally, we explored the
      neural activity of OCD patients during exposure to the autobiographic scenario.
      We proved an increase in beta-3 activity (left frontal lobe). Conclusion: Our
      study proved differences in neural activation in OCD patients and healthy
      controls during imagination of general anxiety. Exposure to the autobiographic
      OCD scenario leads to activation of left frontal brain areas. The results show
      the possibility of using specific scenarios in OCD therapy.

PMID- 30214207
TI  - Aripiprazole combination for reversal of paliperidone-induced increase in
      prolactin level.
AB  - Hyperprolactinemia is a common side effect of antipsychotic drugs. Although
      changes of antipsychotic drugs or reduction of their doses can solve this
      problem, a modification of the treatment regimen can lead to instability in
      patients. Herein, we followed up a patient with elevated prolactin caused by
      paliperidone and found that the prolactin level was decreased after the
      administration of a combination with a low-dose aripiprazole. In addition, we
      summarized and analyzed the findings from the case and the literature review
      conducted.

PMID- 30214208
TI  - Reliability and validity of the Chinese version of Questionnaire - Children with
      Difficulties for Chinese children or adolescents with attention
      deficit/hyperactivity disorder: a cross-sectional survey.
AB  - Purpose: The Questionnaire - Children with Difficulties (QCD) has been developed
      and used to evaluate daily-life problems in children during specified periods of
      the day. The objective of this study was to evaluate the reliability and validity
      of the QCD for Chinese children or adolescents with attention
      deficit/hyperactivity disorder (ADHD). Patients and methods: Outpatients with
      ADHD aged 6-18 years who visited psychiatry clinics were enrolled at four study
      centers in China. Patients with severe psychiatric disorders were excluded.
      Parents of all enrolled patients were given the QCD, the Swanson, Nolan and
      Pelham IV (SNAP-IV), and the Weiss Functional Impairment Scale-Parent (WFIRS-P)
      questionnaires and were asked to complete all three questionnaires. The
      reliability of the QCD was examined by Cronbach's alpha, which assessed the
      internal consistency of the questionnaire. Concurrent criterion validity of QCD
      scores was examined by Spearman's correlation of QCD with SNAP-IV and WFIRS-P
      scores. Results: A total of 200 Chinese patients were analyzed (average age,
      10.4+/-2.66 years). The majority of patients were male (77.5%), and 49.0% had the
      combined ADHD subtype. Cronbach's alpha for QCD was 0.88. Correlation
      coefficients of the QCD total score with SNAP-IV total score and WFIRS-P average
      score were -0.47 and -0.57, respectively. Correlations for the QCD with SNAP-IV
      and WFIRS-P were statistically significant (P<0.01). The area under the curve for
      sensitivity and specificity of the QCD compared with the SNAP-IV and WFIRS-P was
      0.70 and 0.71, respectively. The ADHD severity discrimination threshold range of
      the QCD total score was 30-35. Conclusion: Our study results found the QCD to be
      a reliable and valid instrument and recommend its use in clinical practice to
      identify and evaluate daily-life problems of ADHD patients during specified
      periods of the day in China.

PMID- 30214209
TI  - Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the
      developing brain of rats by enhancing the PI3K/Akt signaling pathway.
AB  - Background: Propofol induces short- and long-term neurotoxicity. Our previous
      study showed that dexmedetomidine (Dex) can attenuate the propofol-induced acute
      neurotoxicity in rodents by enhancing the PI3K/Akt signaling. However, whether
      treatment of young rats with Dex could protect them from long-term neurotoxicity
      induced by propofol is unclear. Materials and methods: Seven-day-old male Sprague
      Dawley rats were randomized and injected intraperitoneally with saline (100 MUL,
      NS), propofol (100 mg/kg), Dex (75 MUg/kg), propofol (100 mg/kg) plus Dex (25, 50
      or 75 MUg/kg), 10% dimethyl sulfoxide (DMSO, 100 MUL) or TDZD-8 (a GSK3beta
      inhibitor, 1 mg/kg), or intracerebroventricularly with DMSO (5 MUL) or LY294002
      (a PI3K inhibitor, 25 MUg/5 MUL DMSO). Other rats in the experimental group were
      injected with the same doses of propofol, Dex and LY294002 or TDZD-8. All the
      rats were monitored until they were 9 weeks old. Their spatial learning and
      memory were tested by Morris water maze. The neuronal apoptosis, expression of
      PSD95, expression and phosphorylation of Akt and GSK3beta and synaptic
      ultrastructures were determined by terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling, immunohistochemistry, Western blot and transmission
      electron microscopy assays, respectively. Results: Compared with the NS control
      group, young rats injected with intralipid, Dex, TDZD-8, LY294002 or DMSO alone
      did not show any significant change as they aged. Propofol significantly
      increased the escape latency time, hippocampal neuroapoptosis and synaptic
      ultrastructural changes but decreased the relative levels of PSD95 expression,
      and Akt and GSK3beta phosphorylation in the developing hippocampus of the rats.
      The neuronal toxic effects of propofol were significantly mitigated by the
      pretreatment with a higher dose of Dex. The neuroprotective effect of Dex was
      enhanced by the treatment with TDZD-8, but was completely abrogated by the
      treatment with LY294002. Conclusion: Our results indicated that the pretreatment
      of young rats with Dex attenuated the propofol-induced long-term neurotoxicity in
      their developing hippocampus by enhancing the PI3K/Akt signaling.

PMID- 30214210
TI  - Investigation of alexithymia and levels of anxiety and depression among patients
      with restless legs syndrome.
AB  - Purpose: The purpose of this study was to examine alexithymia among restless legs
      syndrome (RLS) patients, compare with healthy controls, and argue the clinical
      inferences of this relationship. We searched for anxiety and depression and their
      clinical outcomes among patients and searched whether the results are similar to
      previous studies. Patients and methods: Eighty-seven RLS patients and 88 age,
      gender, and educationally matched healthy controls were assessed in Bezmialem
      Foundation University Hospital. RLS patients and healthy controls were assessed
      with the Sociodemographic Data Form constructed for the present study, 20-item
      Toronto Alexithymia Scale (TAS-20), Beck Depression Inventory (BDI), and Beck
      Anxiety Scale (BAS). The patient group was also assessed with the International
      Restless Legs Syndrome Study Group (IRLSSG) RLS Severity Scale. Results: RLS
      patients were found to have greater TAS-20, BDI, and BAS scores compared with the
      control group (P < 0.05). RLS severity score was positively correlated with the
      scores of anxiety and depression scales. However, no significant relationship was
      found between scores of IRLSSG RLS scale and TAS-20 total and subscale scores.
      Conclusion: RLS patients were found to be more alexithymic than healthy controls,
      whereas no significant relationship was found between RLS severity and levels of
      alexithymia. Still, alexithymia might be a predictor for early diagnosis and may
      be considered in the treatment and follow-up of RLS. RLS patients have higher
      depression and anxiety scores than healthy individuals. Thus, depression and
      anxiety should be taken into consideration throughout the RLS treatment.

PMID- 30214212
TI  - Platelet membrane receptor P2Y12 H1/H2 polymorphism is highly associated with
      cerebral infarction: a case-control study.
AB  - Objectives: This study aimed to determine the relationship between the
      polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and cerebral
      infarction (CI) in a Han population in North Shandong Province, People's Republic
      of China. Patients and methods: A case-control study, which involved 168 nonstoke
      subjects (contrast group) and 152 CI patients (CI group), was conducted. The
      state of subjects in the CI group was validated by computed tomography or MRI.
      The clinical data were categorized into two groups. The data included age,
      gender, smoking, drinking, shrinkage pressure, diastolic blood pressure, blood
      glucose, cholesterol, triglyceride, low-density lipoprotein, high-density
      lipoprotein, serum uric acid, fibrinogen and homocysteine. The polymorphisms were
      genotyped with PCR and restriction fragment length polymorphism analysis. The
      distribution characteristics of nonstoke subjects and CI patients and the
      relationship between the polymorphisms of the H1/H2 gene of platelet membrane
      receptor P2Y12 and ischemic stroke were analyzed. Results: No significant
      difference was found between the contrast group and CI group (P>0.05) in terms of
      age, gender composition, smoking, alcohol consumption, blood glucose,
      cholesterol, triglyceride, low-density protein, high-density lipoprotein
      cholesterol, uric acid and homocysteine. In contrast, significant differences
      were found between these two groups (P<0.01) in terms of SBP, DBP and plasma
      fibrinogen level. The genotyping revealed 112 carriers of the wild-type H1/H1
      genotype and 40 carriers of the mutational H2 allele of P2Y12 H1/H2 in the CI
      group and 140 carriers of the wild-type H1/H1 genotype and 28 carriers of the
      mutational H2 allele of P2Y12 H1/H2 in the contrast group. Furthermore, the H1/H2
      and H2/H2 gene frequencies (26.3%) were significantly higher in the CI group
      (chi2=4.440, P<0.05) than those in the contrast group (16.7%). Moreover, the
      frequencies of the H2 allele in the CI and contrast groups were 14.5% and 8.6%,
      respectively, and the difference was statistically significant (chi2=5.392,
      P<0.05). Multiple logistic regression analysis results revealed that factors
      associated with CI include systolic blood pressure and plasma fibrinogen level,
      which carry the -893T gene. After adjusting for potential confounding factors,
      the H2 allele carriers had a 1.928-fold increased risk for CI (OR=1.928, 95%
      confidence interval: 1.137-3.188; P=0.038) when compared with noncarriers.
      Conclusion: The present study found that hypertension and elevated plasma
      fibrinogen levels are significant risk factors for ischemic stroke and confirmed
      that the H1/H2 and H2/H2 genes of platelet membrane glycoprotein receptor P2Y12
      are risk factors of ischemic stroke.

PMID- 30214213
TI  - Association between platelet distribution width and poor outcome of acute
      ischemic stroke after intravenous thrombolysis.
AB  - Purpose: The platelet distribution width (PDW) reflects the status of platelet
      activity and may be useful for early predictions of the clinical outcome of
      stroke patients. The purpose of the study was to determine the associations
      between PDW and clinical outcomes after intravenous thrombolysis in stroke
      patients. Patients and methods: Acute ischemic stroke patients who received
      intravenous treatment with recombinant tissue-type plasminogen activator were
      selected for inclusion in the retrospective cohort of this study. The relations
      between PDW at admission and clinical outcomes were analyzed, including a poor
      outcome as assessed using the modified Rankin Scale at 3 months, early
      neurological improvement, and any hemorrhage. The effect of PDW at admission on a
      poor outcome at 3 months was analyzed using a multivariable logistic regression
      model with adjustment for potential confounders. The optimal PDW cutoff for
      predicting poor outcome at 3 months was determined by analyzing the receiver
      operating characteristics curve. Results: PDW was significantly higher for a good
      outcome than a poor outcome (p=0.005), with median (interquartile range) values
      of 16.2 (13.2-17.2) and 13.6 (12.5-15.9), respectively. PDW was also higher in
      patients with early neurological improvement than in patients without improvement
      (p=0.020) and did not differ between hemorrhage and nonhemorrhage patients. The
      association between PDW <16.05% and poor outcome remained in a multivariable
      logistic regression analysis, with an OR of 6.68 and a 95% CI of 1.69-26.49
      (p=0.007). Conclusion: Results suggest a novel hypothesis that a lower PDW may be
      related with a poor outcome at 3 months after intravenous thrombolysis in acute
      ischemic stroke patients.

PMID- 30214211
TI  - Relationship between social and cognitive functions in people with schizophrenia.
AB  - Purpose: The purpose of the present study was to examine clinical factors related
      to social function in people with schizophrenia. Patients and methods: The
      participants were 55 stabilized outpatients with schizophrenia. Their mean age
      was 39.36 (SD =10.65) years. Social function was assessed using the Quality of
      Life Scale (QLS). Cognitive function was evaluated with the Measurement and
      Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive
      Battery (MCCB). Clinical symptoms were assessed using the Positive and Negative
      Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia, and the
      Drug-Induced Extrapyramidal Symptoms Scale. Results: Neither the MCCB cognitive
      domain score nor composite score was correlated with the QLS scores. However, of
      the 10 MCCB subtests, the Trail Making Test Part A and the Brief Assessment of
      Cognition in Schizophrenia-Symbol Coding (BACS-SC) scores were positively
      correlated with the QLS scores. Among clinical variables, especially the PANSS
      negative syndrome scale score had a strong negative correlation with the QLS
      scores. Stepwise regression analyses showed that the PANSS negative syndrome
      scale score was an independent predictor of the QLS scores, and although the BACS
      SC score predicted the QLS common objects and activities subscale score, the
      association was not so strong compared to the PANSS negative syndrome scale
      score. Conclusion: These results indicate that speed of processing evaluated by
      BACS-SC could predict some aspect of social function but negative symptoms have a
      much stronger impact on global social function in people with schizophrenia.

PMID- 30214214
TI  - Neurofilament light chain as a biological marker for multiple sclerosis: a meta
      analysis study.
AB  - Purpose: There is a need for biomarkers in multiple sclerosis (MS) to make an
      early diagnosis and monitor its progression. This study was designed to evaluate
      the value of neurofilament light (NFL) chain levels as cerebrospinal fluid (CSF)
      or blood biomarker in patients with MS by using a quantitative meta-analysis.
      Methods: The PubMed, Embase, and Web of Science databases were systematically
      searched for relevant studies. Articles in English that evaluated the utility of
      NFL in CSF and blood in the diagnosis of MS were included. Data were extracted by
      two independent researchers. Mean (+/- SD) NFL concentration for MS patients and
      control subjects were extracted. Review Manager version 5.3 software with a
      continuous-variable random-effects model was used to summarize the diagnostic
      indexes from eligible studies. The Newcastle-Ottawa Scale was used for assessing
      the quality and risk of bias of included studies. In addition, subgroup analysis
      and meta-regression were performed to assess potential heterogeneity sources.
      Results: The meta-analysis included 13 articles containing results from 15
      studies. A total of 10 studies measured NFL levels in CSF and five studies
      measured NFL levels in blood. Data were available on 795 participants in CSF and
      1,856 participants in blood. Moreover, CSF NFL in MS patients was higher than
      that in healthy control groups (pooled standard mean difference [Std.MD]=0.88,
      95% CI [0.50, 1.26], P<0.00001) and serum NFL in MS patients was higher than that
      in control subjects (pooled Std.MD=0.47, 95% CI [0.24, 0.71], P<0.0001).
      Conclusion: NFL chain has significantly increased in MS patients, which
      substantially strengthens the clinical evidence of the NFL in MS. The NFL may be
      used as a prognostic biomarker to monitor disease progression, disease activity,
      and treatment efficacy in the future.

PMID- 30214215
TI  - What is the role of adipokines in myasthenia gravis?
AB  - Objective: Myasthenia gravis (MG) is a disease with autoimmune etiology. The main
      pathomechanism is related to the production of antibodies against nicotinic
      acetylcholine receptor. The present study is aimed to compare the serum level of
      adipokines in patients with MG with that in controls, as well as to study the
      relation of these levels with disease severity. Patients and methods: Fifty
      patients with MG and 30 healthy individuals were enrolled in our study. Serum
      concentrations of select adipokines, namely adiponectin, leptin, omentin,
      visfatin, and resistin were measured. Results: The results showed a significant
      increase in serum concentrations of adiponectin and resistin in the patients with
      MG compared with the controls. Conclusion: Further studies are warranted to
      assess changes in adipokine concentration levels in patients with MG.

PMID- 30214216
TI  - Diagnostic value of PD-1 mRNA expression combined with breast ultrasound in
      breast cancer patients.
AB  - Introduction: This study explored the value of measuring programmed death 1 (PD
      1) in peripheral blood, combined with breast ultrasound using the Breast Imaging
      Reporting and Data System (BI-RADS) classification, for differentiation between
      benign and malignant breast tumors. Materials and methods: We enrolled 113
      patients with breast cancer and 66 patients with benign breast tumors who were
      admitted to Hangzhou First People's Hospital from September 2014 to August 2017.
      The mRNA level of PD-1 was detected by quantitative real-time polymerase chain
      reaction. Results: The mRNA levels of PD-1 were significantly higher in the
      peripheral blood of patients with breast cancer than those in patients with
      benign breast tumors. The diagnostic sensitivity of PD-1 mRNA expression was
      0.805, the specificity was 0.788, and the area under the curve (AUC) was 0.848 (P
      < 0.001); the sensitivity of breast ultrasound-based BI-RADS classification was
      0.752, the specificity was 0.909, and the AUC was 0.906 (P < 0.001); and the
      combined sensitivity, specificity, and AUC of the two assays were 0.920, 0.879,
      and 0.938, respectively (P < 0.001). Progesterone receptor-positive breast cancer
      patients exhibited high levels of PD-1 expression (P < 0.001). Conclusion: This
      study suggests that the measurement of PD-1 combined with breast ultrasound-based
      BI-RADS classification represents a significant improvement for breast cancer
      diagnosis compared with diagnoses based on either method alone.

PMID- 30214218
TI  - Rare complications of neurofibromatosis 1 diagnosed incidentally in two children.
AB  - Neurofibromatosis 1 (NF1) is an autosomal-dominant disorder with various clinical
      expressivity and complications. Arterial hypertension may be present in patients
      with NF1 and is secondary to vasculopathy or pheochromocytoma. We herein describe
      two children (17 and 4 years old) diagnosed late with NF1 after severe arterial
      hypertension had been discovered due to pheochromocytoma and middle aortic
      syndrome. Routine measurement of arterial pressure is mandatory in children with
      NF1, in order to diagnose the complications of this disease.

PMID- 30214217
TI  - The effects of AER and eGFR on outcomes of CVD in patients with T2DM in an urban
      community over 8 years of multifactorial treatment: the Beijing Communities
      Diabetes Study 18.
AB  - Objective: It is well known that diabetic kidney disease is a risk factor for
      cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM).
      In this study, the effects of urine albumin excretion rate (AER) and estimated
      glomerular filtration rate (eGFR) on CVD outcomes were analyzed in a population
      of T2DM. Methods: The study was carried out using recorded information of a
      cohort study. A total of 1,914 patients with T2DM with no prevalent CVD were
      enrolled in an 8 years prospective study and received multifactorial
      intervention. The risk of CVD outcomes was assessed according to chronic kidney
      disease staging, which was categorized using AER (mg/d) and eGFR (mL/min/1.73
      m2). The effects of AER and eGFR on risk of CVD onset were also analyzed.
      Results: During the follow-up period (median 6.8 years), 71 CVD events occurred.
      At baseline, those with AER >=300 mg/d and coexisting eGFR 60-89 mL/min/1.73 m2
      or <60 mL/min/1.73 m2 showed increased risk for CVD outcomes when compared with
      "no chronic kidney disease" (AER <30 mg/d and eGFR >=90 mL/min/1.73 m2). The
      increased CVD risk was observed in patients who progressed to AER >=30 mg/d
      during the follow-up period, whereas patients who progressed to eGFR <90
      mL/min/1.73 m2 alone showed no increased CVD risk. During the follow-up period,
      after multifactorial intervention, 8.7% patients with microalbuminuria and 1.8%
      patients with overt nephropathy reversed to normoalbuminuria or microalbuminuria.
      Conclusion: AER is a more sensitive predictor than eGFR for CVD outcomes in T2DM
      patients. Overt nephropathy can be reversed after multifactorial intervention.

PMID- 30214219
TI  - Prognosis of patients with pulmonary embolism after rehabilitation.
AB  - Introduction: Pulmonary embolism (PE) is a life-threatening disease; in Germany,
      therefore, rehabilitation after PE is recommended in patients with intermediate-
      and high-risk PE. However, no prospective data on PE after inpatient
      rehabilitation have been published so far. Patients and methods: For this
      monocentric study, 70 patients with PE were prospectively recruited between
      November 2013 and November 2014 after giving written informed consent. This study
      was approved by the ethics committee of the Medical Association of Saxony-Anhalt.
      Inclusion criteria were as follows: age >=18 years and a stay at the Paracelsus
      Harz Clinic in Bad Suderode, Germany, with the main indication of PE. During the
      hospital stay, history-relevant medical data and diagnostic findings were
      collected and documented. Furthermore, we recorded whether patients were
      rehospitalized or died during the treatment period in the rehabilitation clinic
      or during the 12-month follow-up. Results: The mean age was 64.5 +/- 13.0 years,
      the mean body mass index (BMI) was 30.4 +/- 6.0 kg/m2, and 54.3% were women.
      During rehabilitation, two patients (3.9%) were transferred to a primary care
      hospital; no patient died. However, four patients died (5.7%) in the 12-month
      follow-up period. A total of 20 patients were hospitalized in the 12-month follow
      up period (hospitalization rate during the 12-month follow-up period: 28.6%). Of
      these 20 patients, one patient was rehospitalized with a newly diagnosed PE
      (1.4%) and two patients were rehospitalized for bleeding events (2.8%).
      Conclusion: PE is a life-threatening disease, and therefore it seems reasonable
      to recommend rehabilitation at least in patients with an intermediate- or high
      risk PE. In this study, death and other serious event rates were low during the
      in-hospital rehabilitation and in the 12-month follow-up period, which underlined
      the safety and importance of a standardized rehabilitation program after survived
      PE.

PMID- 30214220
TI  - Clinical accuracy of the Omron M3 Comfort(r) and the Omron Evolv(r) for self
      blood pressure measurements in pregnancy and pre-eclampsia - validation according
      to the Universal Standard Protocol.
AB  - Background: Electronic devices for blood pressure (BP) measurements need to go
      through independent clinical validation as recommended by different authorities,
      both in general and in special populations such as pregnancy. Objective: To
      evaluate the accuracy of the Omron Evolv(r) (HEM-7600T-E) and the Omron M3
      Comfort(r) (HEM-7134-E) devices in pregnancy and pre-eclampsia according to the
      Universal Standard Validation Protocol. Methods: Both devices, the Evolv and the
      M3 Comfort, measure BP at the brachial level using the oscillometric method. The
      study was performed according to the recently published protocol, the so-called
      "modified Advancement of Medical Instrumentation (AAMI)/British Hypertension
      Society (BHS)/European Society of Hypertension (ESH) protocol" or the "Universal
      Standard Protocol." Validation of each device included 45 pregnant women in the
      second and third gestational trimester of whom 15 had pre-eclampsia, 15 had
      gestational hypertension and 15 were normotensives. BP differences between the
      observer and the device BP values were classified into three categories (<=5,
      <=10, and <=15 mmHg) and the mean BP differences (test vs reference) and its SD
      were calculated. Results: Both devices, the Evolv and the M3 Comfort, achieved a
      grade A/A in both pregnancy and pre-eclampsia. The mean difference (SD) between
      the mercury standard and the device BP values in pregnancy were: 1) for the Evolv
      of -0.7+/-2.3 mmHg for systolic blood pressure (SBP) and -0.1+/-1.8 mmHg for
      diastolic blood pressure (DBP); 2) for the M3 Comfort of -1.6+/-2.8 mmHg for SBP
      and -0.1+/-2.3 mmHg for DBP. Conclusion: Both devices, the Evolv and the M3
      Comfort, achieved a grade A/A for both SBP and DBP and fulfill the validation
      protocol criteria in pregnancy and pre-eclampsia. Consequently, these two devices
      can be recommended for home BP measurements in this specific population.

PMID- 30214221
TI  - Multidisciplinary team approach in the management of popliteal artery injury.
AB  - Popliteal artery injuries (PAIs) remain a challenging entity and carry the
      greatest risk of limb loss among traumatic lower extremity vascular injuries.
      Operative management of traumatic popliteal vascular injuries continues to
      evolve. Improved diagnostic imaging and the introduction of endovascular
      techniques offered alternative modalities to traditional surgical management.
      Despite major efforts in establishing protocols and guidelines in the management
      of vascular trauma, optimal strategies of traumatic PAIs are still under
      investigation. Herein, we discussed the role of multidisciplinary team, involving
      trauma and endovascular surgeons, emergency department personnel, and
      interventional radiologists in the management of complex PAIs.

PMID- 30214222
TI  - Reducing HIV-related stigma and discrimination in healthcare settings: a
      systematic review of guidelines, tools, standards of practice, best practices,
      consensus statements and systematic reviews.
AB  - Introduction: Policy makers and health professionals prefer to use preappraised
      and summarized evidence. Stigma and discrimination (SAD) reduction activities and
      programs are needed to improve the quality of care delivered to people living
      with HIV and the success of HIV-related prevention, care and treatment programs.
      The objective of this review was to identify and describe systematic reviews,
      best practices, consensus statements, standards of practice and guidelines that
      addressed SAD among healthcare workers (HCWs). Methods: All documents in the form
      of systematic reviews, best practices, consensus statements, standards of
      practice and guidelines were considered for inclusion. The search strategy aimed
      to find both published and unpublished studies reported in English with unlimited
      date range in Excerpta Medica Database from Elsevier (EMBASE), Cumulative Index
      to Nursing and Allied Health (CINAHL), Psychological Information (PsycINFO)
      database and Medical Literature Analysis and Retrieval System Online (MEDLINE).
      Websites of organizations and guideline databases were also searched. Two
      individuals independently appraised the quality of the documents using the
      Appraisal of Guidelines for Research and Evaluation (AGREE II) checklist and the
      Joanna Briggs Institute critical appraisal checklist for systematic reviews. Data
      extraction was done using a customized tool that was developed to record the key
      information of the source that is relevant to the review question. Results:
      Twelve records (six guideline-related documents and six systematic reviews) were
      included in the review. Interventions and recommendations developed to reduce HIV
      related SAD were categorized into information-based, structural, biomedical,
      counseling and support, skills building and contact interventions. Conclusion:
      Implications for practice: Interventions that reduce HIV-related SAD are broadly
      categorized into information-based, structural, biomedical, counseling and
      support, skills building and contact interventions. Because of limited
      methodological description of the included documents, it was difficult to draw
      recommendations for policy and practice. Implications for research: Future
      studies need to use up-to-date instruments to measure SAD. Further studies of
      greater methodological quality are needed. Guidelines, tools and best practice
      documents that aim to reduce HIV-related SAD should be developed with the
      considerations of research evidence on the specific setting and specific targeted
      populations.

PMID- 30214223
TI  - Using information and communication technology in the recovery after a coronary
      artery bypass graft surgery: patients' attitudes.
AB  - Background: Patients who have undergone a coronary artery bypass graft (CABG)
      surgery are exposed to physical and mental problems after discharge from the
      specialist hospital and are often in need of post-discharge support and follow
      up. Aim: This study aimed to explore the attitudes of CABG patients toward using
      information and communication technology (ICT) during the first year of recovery
      after discharge from hospital. Methods: A cross-sectional design utilizing an
      electronic survey was employed. The sample consisted of 197 patients who had
      undergone a CABG surgery during 2015. The questionnaire included questions about
      follow-up needs, contacts with health professionals, use of the Internet, and
      attitudes toward using ICT in the recovery phase. Results: Mean age of the
      participants was 67.3 years; 18.3% were women. A total of 48.2% of the patient
      group was satisfied with the pre-discharge information. Only 27% had contacted
      the hospital after discharge. Whereas 58.4% of the participants had used the
      Internet to acquire information, only 30.4% found this information to be useful.
      Many patients (40%) reported that they could benefit from online health
      information and Skype meetings with professionals. More than 30% reported that
      nutritional guidance on the Internet could be motivating for choosing healthy
      diets, and 42.6% reported that Internet-based illustrative videotapes could be
      motivating for undertaking physical training. Conclusion: ICT can be useful and
      resource-saving for patients who have undergone a CABG surgery, as well as for
      the health care services. The technology must be appropriately tailored, with
      regard to content and design, to be helpful for patients.

PMID- 30214224
TI  - 125I seed brachytherapy versus external beam radiation therapy for the palliation
      of painful bone metastases of lung cancer after one cycle of chemotherapy
      progression.
AB  - Purpose: This study aimed to compare the outcomes of 125I seed brachytherapy
      versus external beam radiation therapy (EBRT) for the palliation of painful bone
      metastases of lung cancer after one cycle of chemotherapy progression. Materials
      and methods: We analyzed retrospectively 158 patients with painful bone
      metastases secondary to lung cancer after one cycle of chemotherapy progression
      treated between June 2013 and May 2016. Seventy-six patients with 96 lesions
      received 125I brachytherapy (Group A), whereas 82 patients with 98 metastases
      received EBRT (Group B). Pain intensity on Brief Pain Inventory, percentage of
      patients with pain severity, and quality of life were recorded prior to treatment
      (T0), 2, 4, 6, 8, 12, 16, 20, and 24 weeks (T2, T4, T6, T8, T12, T16, T20, and
      T24) after treatment during a 24-hour period. Cost-effectiveness and number of
      treatment appointments were also compared between groups. Results: One hundred
      and fifty-eight patients had been treated. Visual analog scale for worst pain in
      Group A was significantly lower than in Group B at T2, T4, T6, T16, T20, and T24.
      Group A was superior to group B concerning quality of life scores (T2, T4, T20,
      and T24), cost-effectiveness, and number of treatment appointments. No
      significant differences were observed for complications. Conclusion: Compared
      with EBRT, 125I seed brachytherapy can be an alternative method for painful bone
      metastases from lung cancer after one cycle of chemotherapy progression.

PMID- 30214225
TI  - Alternative treatment strategies to sorafenib in patients with advanced
      hepatocellular carcinoma: a meta-analysis of randomized Phase III trials.
AB  - Introduction: This meta-analysis was conducted to evaluate efficacy and safety in
      patients treated with sorafenib vs other tyrosine-kinase inhibitors (TKIs) or
      selective internal radiotherapy (SIRT) for advanced hepatocellular carcinoma
      (HCC). Methods: Electronic databases were systematically reviewed for randomized
      Phase III trials comparing sorafenib with other TKIs or SIRT in advanced HCC.
      Sorafenib was defined as the control arm. Other TKIs or SIRT was defined as the
      experimental arm. Overall survival (OS), time to progression (TTP), objective
      response rate (ORR), disease-control rate (DCR), and adverse events (AEs) were
      reviewed. Four trials in the other-TKI group (n=4,218) and two in the SIRT group
      (n=819) were eligible. Results: Compared with sorafenib, other TKIs showed
      similar benefit on OS (HR 1.08, 95% CI 0.93-1.24; P=0.31) and TTP (HR 0.86, 95%
      CI 0.66-1.12; P=0.26) for advanced HCC. A significant increase in ORR (RR 1.67,
      95% CI 1.15-2.43; P=0.008) was found with other TKIs, but no increase in DCR (RR
      1.11, 95% CI 0.98-1.26; P=0.11) was observed. Other TKIs were associated with
      more frequent grade 3/4 AEs than sorafenib, including hypertension (P<0.00001),
      thrombocytopenia (P=0.002), fatigue (P<0.00001), decreased appetite (P<0.00001),
      and vomiting (P<0.0001). For locally advanced HCC, neither OS (HR 1.14, 95% CI
      0.98-1.32; P=0.09) nor TTP (HR 0.87, 95% CI 0.74-1.02; P=0.10) differed
      significantly in SIRT and sorafenib. There was an increase in ORR (RR 2.60, 95%
      CI 1.69-4.00; P<0.0001), but no improvement in DCR (RR 0.91, 95% CI 0.81-1.02;
      P=0.11) in the SIRT group. Fewer patients treated with SIRT had grade 3/4 AEs
      than those treated with sorafenib, including diarrhea (P<0.0001), fatigue
      (P=0.0006), and hand-foot syndrome (P=0.0002). Other TKIs were noninferior to
      sorafenib in OS and TTP in advanced HCC, but with increased risk of toxicities.
      Conclusion: Patients with locally advanced HCC treated with SIRT got similar
      efficacy with less toxicity to those treated with sorafenib.

PMID- 30214226
TI  - Radiotherapy for one rectal cancer patient with cirrhosis and moderate to severe
      thrombocytopenia: a case report.
AB  - When patients with cirrhosis and severe thrombocytopenia suffer malignant tumors,
      there is usually no effective and feasible treatment method due to the high risk
      of hemorrhage. Herein, we report a case in which radiotherapy was given to a
      patient with a strong desire for the treatment. The patient was a 66-year-old man
      with a 13-year history of cirrhosis and a 10-year history of thrombocytopenia,
      and was diagnosed with locally advanced rectal cancer (LARC; T4aN1M0, stage
      IIIB). The platelet count before radiotherapy was 32 * 109/L, and the blood
      coagulation was normal. The severity of thrombocytopenia increased after 2 Gy * 7
      fractions pelvic radiation, with platelet counts dropping to 16 * 109/L. Platelet
      counts failed to return to pre-therapy levels after supporting therapy including
      recombinant human interleukin 11 subcutaneous injection and platelet transfusion.
      Although radiotherapy was discontinued eventually, the data presented here
      represent a valuable resource that can help inform treatment decisions for tumor
      patients with cirrhosis and thrombocytopenia.

PMID- 30214227
TI  - Magnolol exerts anticancer activity in hepatocellular carcinoma cells through
      regulating endoplasmic reticulum stress-mediated apoptotic signaling.
AB  - Introduction: Magnolol (Mag), a biologically active compound isolated from the
      root and stem bark of Magnolia officinalis, has been reported to induce apoptosis
      in several cancer cell lines in vitro. In the present study, we aimed to
      determine the anticancer effects of Mag on hepatocellular carcinoma (HCC) cells.
      Materials and methods: The HepG2 cells were treated with varying concentrations
      of Mag (10, 20, and 30 MUM) for 48 hours. The effects of Mag on the
      proliferation, migration, invasion, apoptosis and cell cycle progression of HepG2
      cells were respectively detected by MTT assay, transwell assays, and flow
      cytometric analysis. A HepG2 cell-based tumor-bearing model was established to
      evaluate the effect of Mag on HCC tumor growth in vivo. The protein expression
      levels were determined by Western blot analysis. Results: Our results showed that
      Mag inhibited the proliferation, migration, and invasion of HepG2 cells in vitro
      in a dose-dependent manner. In addition, Mag reduced the HCC tumor volume and
      weight in the mouse xenograft model. Subsequent studies showed that Mag induced
      apoptosis in HepG2 cells, accompanied by a loss in mitochondrial membrane
      potential, cytochrome c release, and induction of endoplasmic reticulum stress.
      Furthermore, inhibition of the endoplasmic reticulum stress by CHOP knockdown
      restored the effects of Mag in HepG2 cells. Conclusion: The present study
      highlighted the possibility of using Mag as a novel therapeutic drug for HCC
      treatment.

PMID- 30214228
TI  - Surgical therapy and next-generation sequencing-based genetic alteration analysis
      of malignant solitary fibrous tumor of the pleura.
AB  - Background: Solitary fibrous tumor of the pleura (SFTP) is a rare pleural
      neoplasm arising from mesenchymal cells, accounting for <5% of pleural neoplasms.
      Approximately 10% of cases of SFTP demonstrate malignant potential, leading to
      local recurrence after radical surgery and subsequent metastasis. Methods: A
      large malignant-like mass was found in the left thoracic cavity of a 61-year-old
      woman. Following radical resection of the mass, the patient was diagnosed with
      malignant SFTP by histologic and immunohistochemical analyses. In addition, a
      next-generation sequencing-based mutation test was used to reveal the mutational
      profile of the tumor. The genetic alteration panel was analyzed with reference to
      public data on the ClinVar and COSMIC databases, after which the public SFTP data
      were analyzed for frequency of altered genes. Finally, through overlay of the
      abovementioned two sets, the genetic alteration accounting for SFTP initiation
      was anticipated to be identified. Results: In the mutation panel of our malignant
      SFTP group, kinase insert domain receptor (KDR) and fms-related tyrosine kinase 1
      (FLT1) scored high in pathogenesis but had only a medium frequency; the NAB2
      STAT6 fusion appeared to be the dominant genetic alteration in public SFTP
      samples. Conclusion: The high frequency of NAB2-STAT6 fusion indicates its
      prominent role in SFTP, while somatic mutations such as FLT1-R593W and KDR-V297I
      may also contribute to the malignant angiogenic phenotype. The present study
      affirmed the heterogeneity of SFTP, and more sophisticated classification methods
      will be needed to explore its underlying mechanisms. Summary: We believe that
      improvement in the prognosis of SFTP relies on early diagnosis, margin-free
      resection, and long-term follow-up. Through genetic analysis, it appears that
      both NAB2-STAT6 fusion and somatic mutations such as FLT1-R593W and KDR-V297I
      contribute to SFTP development.

PMID- 30214229
TI  - miR-361-5p inhibits glioma migration and invasion by targeting SND1.
AB  - Background: Downregulation of miR-361-5p contributes to epithelial-mesenchymal
      transition of glioma cells. However, the relevance of miR-361-5p to migration and
      invasion of gliomas remains unknown. Materials and methods: The relationship
      between miR-361-5p and SND1 expression was analyzed in 120 human gliomas and 8
      glioma cell lines by in situ hybridization, immunohistochemistry, and Western
      blot. Dual-luciferase reporter assay was used to identify SND1 as a target of miR
      361-5p. The mechanisms through which miR-361-5p inhibits glioma cell migration
      and invasion were studied by in vitro assays. Results: miR-361-5p expression was
      significantly downregulated in glioma tissues and glioma cell lines, and was
      inversely correlated with glioma grades. However, SND1 expression was positively
      correlated with glioma grades and inversely correlated with miR-361-5p
      expression. miR-361-5p overexpression suppressed glioma cell migration and
      invasion through targeting SND1 and subsequently decreasing MMP-2 expression. In
      glioma cell lines, SND1 overexpression could partly reverse the antitumor effects
      of miR-361-5p. Conclusion: The findings provide evidence that miR-361-5p directly
      targets SND1 to degradation and then reduces MMP-2 gene transcription, thus
      inhibiting glioma migration and invasion. miR-361-5p is an important tumor
      suppressor and a novel diagnostic biomarker of glioma, and miR-361-5p and SND1
      are potential therapeutic candidates for malignant gliomas.

PMID- 30214230
TI  - Profile of abemaciclib and its potential in the treatment of breast cancer.
AB  - Hormone-receptor-positive breast cancer is the most common subtype of breast
      cancer among patients with both early-stage and metastatic disease. Recent
      advances in the understanding of its pathophysiology have led to the discovery
      and utilization of targeted inhibitors to cyclin-dependent kinases 4 and 6
      (CDK4/6). There are currently three available CDK4/6 inhibitors available for use
      in USA: palbociclib, ribociclib, and abemaciclib. Their oral administration and
      tolerable toxicities make this class of agents appealing to both patients and
      health care providers. Abemaciclib, the most recently approved CDK4/6 inhibitor,
      has unique pharmacologic properties and potential toxicities. This review
      highlights the current understanding of abemaciclib and discusses its current and
      future roles in the treatment of breast cancer.

PMID- 30214231
TI  - Prognostic role of aspartate aminotransferase-lymphocyte ratio index in patients
      with metastatic colorectal cancer: results from the randomized ITACa trial.
AB  - Background: The aim of this study was to investigate the role of pre-treatment
      aspartate aminotransferase-lynphocyte ratio (ALRI) as a predictor of prognosis
      and treatment efficacy in patients with metastatic colorectal cancer (mCRC)
      enrolled in the prospective multicenter randomized ITACa (Italian Trial in
      Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) +
      bevacizumab (B) or CT alone. Patients and methods: Patients randomly received
      CT+B or CT alone as first-line therapy. CT consisted of either FOLFOX4 or FOLFIRI
      at the clinician's discretion. Results: Out of the 284 patients enrolled,
      increased ALRI levels were associated with shorter PFS and OS (p<0.0001). At
      baseline, median PFS was 10.3 months (95% CI 9.4-12.0) and 8.0 months (95 % CI
      6.8-8.9), and median OS was 25.2 months (95 % CI 21.3-30.2) and 18.8 months (95 %
      CI 16.6-21.7) for patients with low (<14) and high (>=14) ALRI levels,
      respectively (HR 1.43, 95% CI 1.12-1.82, p=0.004; HR=1.51, 95% CI 1.17-1.96,
      p<0.001). Interaction tests on ALRI levels and treatment efficacy in the CT+B and
      the CT groups were statistically significant for PFS (p=0.0003), but not for OS
      (p=0.228). Conclusion: Our results indicate that ALRI is a good prognostic and
      predictive marker for mCRC patients candidate for CT+B.

PMID- 30214232
TI  - Long noncoding RNA Sox2 overlapping transcript (SOX2OT) promotes non-small-cell
      lung cancer migration and invasion via sponging microRNA 132 (miR-132).
AB  - Background: Long noncoding RNA (lncRNA) Sox2 overlapping transcript (SOX2OT) has
      been reported to be upregulated in various types of cancers, including non-small
      cell lung cancer (NSCLC). However, the biological role and underlying mechanism
      of SOX2OT activity in NSCLC remain largely unknown. This study aims to
      investigate the function and possible molecular mechanisms of SOX2OT in NSCLC.
      Materials and methods: Quantitative real-time polymerase chain reaction was used
      to detect SOX2OT expression, and cellular proliferation, migration, and invasion
      were measured using cell counting kit-8, wound healing, and Transwell invasion
      assays, respectively. Western blotting was used to determine protein expression.
      Starbase 2.0 and luciferase reporter assay were utilized to identify the
      molecular target of SOX2OT. Results: Here, we discovered that SOX2OT was markedly
      upregulated in NSCLC tissues and cell lines. Knockdown of SOX2OT inhibited the
      proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT)
      process in NSCLC cells. Moreover, we explored the regulatory mechanism of SOX2OT
      and found that SOX2OT directly bound microRNA 132 (miR-132) in NSCLC cells.
      Importantly, miR-132 inhibition partially reversed the SOX2OT knockdown-mediated
      inhibitory effect on cell proliferation, migration, invasion, and EMT process. We
      also found that SOX2OT could regulate zinc finger E-box-binding homeobox 2 (a
      target of miR-132) expression, which played crucial roles in tumor cell
      proliferation and invasion. Conclusion: These findings indicated that SOX2OT was
      a noncoding oncogene that exerted important regulatory functions in NSCLC via
      sponging miR-132 and might represent a novel strategy for overcoming this
      disease.

PMID- 30214233
TI  - Microsurgical treatment of parafalcine meningiomas: a retrospective study of 126
      cases.
AB  - Objective: To discuss the diagnosis, operation methods, and clinical effects of
      parafalcine meningiomas. Methods: The clinical and preoperative imaging
      characteristics, operative methods, and effects of operations of 126 cases of
      parafalcine meningiomas were respectively discussed. Results: G1 resection was
      achieved in 13 cases, G2 in 105 cases, G3 in four cases, and G4 in four cases,
      with no deaths. Among these, there were 16 patients with dyskinesia of the
      contralateral extremities after surgery, but they recovered after several months.
      Conclusion: In order to avoid postoperative complications, we consider it vital
      to analyze the patients' condition, the anatomy of venous drainage in by digital
      subtractional angiography, the relationship between tumor location and brain
      tissue according to MRI, and to remove the tumor in an adequately exposed
      surgical field.

PMID- 30214234
TI  - Successful treatment of relapsed testicular embryonal rhabdomyosarcoma with
      Endostar and traditional chemotherapy: a case report.
AB  - Embryonal rhabdomyosarcoma (ERMS) has a low prevalence, poor prognosis, and
      limited treatment efficacy. We report a case of an 18-year-old male whose disease
      relapsed in the abdominal cavity after a testicular ERMS curative resection. The
      patient received eight sequential cycles of rescue therapy using cisplatin and
      isocyclophosphamide in combination with a vascular targeted drug, Endostar. The
      therapeutic effect of the combination regimen has been evaluated for complete
      response. This is the first case to report using Endostar and chemotherapy in
      relapsed ERMS, and the curative effect results in complete response. Endostar, a
      new vascular targeted drug, combined with chemotherapy may play a synergistic
      role and provide a reference for the treatment of ERMS.

PMID- 30214235
TI  - miR-376a inhibits breast cancer cell progression by targeting neuropilin-1 NR.
AB  - Background: The roles and related mechanism of miR-376a in breast cancer cell
      progression are unclear. Methods: Kaplan-Meier plotter analysis was used to
      analyze the correlation between miR-376a and the overall survival (OS) of breast
      cancer patients. Quantitative reverse transcription polymerase chain reaction
      (qRT-PCR) was performed to detect miR-376a level in breast cancer cells. Cell
      viability, transwell migration and invasion, and cell apoptosis were constructed
      to investigate the effects of miR-376a on breast cancer cells. Luciferase
      reporter and RNA immunoprecipitation (RIP) were used to explore the targeting of
      miR-376a on NRP-1. Results: miR-376a expression was positively correlated with
      the overall survival of breast cancer patients, and significantly decreased in
      breast cancer cells. Functionally, miR-376a over-expression suppressed cell
      proliferation, migration and invasion, and promoted cells apoptosis.
      Additionally, miR-376a could directly target NRP-1 and exerted its effect through
      NRP-1. Conclusion: miR-376a could suppress breast cancer cell progression via
      directly targeting NRP-1.

PMID- 30214236
TI  - E2F3 promotes cancer growth and is overexpressed through copy number variation in
      human melanoma.
AB  - Introduction: Melanoma is a malignant tumor that seriously affects patients. The
      pathogenesis of malignant melanoma is complex, and the cell cycle is closely
      related to tumor progression. Based on the catalog of cancer somatic mutations,
      we found that overexpression of the E2F3 gene ranked first in percentage increase
      in not only melanoma but also in all human cancer tissues. However, there are few
      studies on the high expression of E2F3 and its carcinogenic mechanism in
      melanoma. Methods and results: We found that E2F3 showed extensive copy number
      amplification that was positively correlated with the expression level. Patients
      with high copy number had a significantly poorer prognosis. We also found that
      E2F3 levels were significantly negatively correlated with promoter methylation.
      However, we showed that the E2F3 promoter region is hypomethylated, and in normal
      cells or tumor cells, the methylation level did not correlate with expression.
      Finally, we knocked down the E2F3 gene in melanoma cells by shRNA. Colony
      formation, anchorage-dependent growth, and EdU cell proliferation experiments
      showed a significant decrease in proliferation. Flow cytometry showed a
      significant increase in the G0/G1 ratio. Conclusion: It can be speculated that
      copy number amplification and other mechanisms result in the high expression of
      E2F3 in melanoma, which promotes tumor progression by involving the cell cycle.
      E2F3 is a good target for the treatment of melanoma.

PMID- 30214237
TI  - Eukaryotic translation initiation factor 3 subunit G (EIF3G) resensitized
      HCT116/5-Fu to 5-fluorouracil (5-Fu) via inhibition of MRP and MDR1.
AB  - Purpose: Colorectal cancer (CRC) has become a predominant cancer and accounts for
      approximately 10% of cancer-related mortality. Drug resistance still remains a
      priority mortality factor for patients due to no available therapeutic
      alternatives. The purpose of the present study was to investigate the underlying
      molecular mechanisms how eukaryotic translation initiation factor 3 subunit G
      (EIF3G) resensitized 5-Fu-resistant human CRC cells (HCT116/5-Fu) to 5
      fluorouracil (5-Fu). Methods: Multiple cellular and molecular biology experiments
      were performed in the present study, such as CCK-8, western blotting and flow
      cytometry. Results: We found that EIF3G is highly expressed at RNA and protein
      levels in HCT116/5-Fu cells compared with HCT116 cells using quantitative real
      time polymerase chain reaction and Western blot analysis. In addition, silencing
      EIF3G enhanced 5-Fu-induced apoptosis in HCT116/5-Fu cells. Moreover, EIF3G
      silencing decreased the activity of the drug-related proteins MDR1 and MRP levels
      in HCT116/5-Fu cells. Finally, the xenograft tumor model further confirmed that
      EIF3G resensitized HCT116/5-Fu tumors to 5-Fu. We observed that EIF3G silencing
      followed by 5-Fu administration had a synergistic interaction effect on HCT116/5
      Fu in vitro and in vivo. Conclusion: These findings demonstrate that EIF3G is a
      targetable regulator of chemoresistance in CRC, and inhibiting EIF3G in
      combination with 5-Fu might be a potential therapeutic strategy for colon cancer.

PMID- 30214238
TI  - Prognostic role of long non-coding RNA HNF1A-AS1 in Chinese cancer patients: a
      meta-analysis.
AB  - Background: Long non-coding RNAs (LncRNAs) play important roles in tumorigenesis
      and progression. Recent studies have demonstrated that LncRNA HNF1A antisense RNA
      1 (HNF1A-AS1) is aberrantly expressed in several types of cancers and is
      associated with poor outcomes. This meta-analysis was conducted to investigate
      the relationship between HNF1A-AS1 expression and clinical outcomes in cancer
      patients. Methods: We searched PubMed, Embase, Web of Science, China National
      Knowledge Infrastructure (CNKI), and Wan Fang databases (updated until December
      31, 2017) for literature. A total of eight studies with 789 cancer patients were
      finally included in the present meta-analysis. Results: The results showed that
      high expression of HNF1A-AS1 significantly predicted poor overall survival
      (HR=3.10, 95% CI: 1.58-6.11, P=0.001), which was further validated using The
      Cancer Genome Atlas (TCGA) dataset. Moreover, high HNF1A-AS1 expression was also
      associated with advanced TNM stage (OR=3.32, 95% CI: 2.28-4.83, P<0.001), lymph
      node metastasis (OR=3.08, 95% CI: 1.95-4.85, P<0.001), and distant metastasis
      (OR=5.53, 95% CI: 1.94-15.77, P=0.001). Conclusion: Our results suggested that
      elevated HNF1A-AS1 was associated with poor clinical outcomes and might serve as
      a potential prognostic biomarker of cancer.

PMID- 30214239
TI  - Apatinib mesylate tablet in the treatment of advanced malignant melanoma.
AB  - Background: Observing and studying clinical efficacy and safety of apatinib
      mesylate tablet in the treatment of advanced malignant melanoma (MM). Methods:
      Retrospectively analyzing the clinical data of 22 patients with metastatic MM who
      had failed conventional chemotherapy from June 2016 to January 2018. All patients
      took 500 mg of apatinib mesylate tablets per day. The efficacy should be
      evaluated according to RECIST 1.1 criteria. Adverse events (AEs) should be graded
      according to NCI-CTCAE 4.0. Results: There were two cases of partial remission
      (PR), 11 of stable disease (SD) and nine of progressive disease (PD) in the 22
      patients with advanced MM, where the objective remission rate (ORR) was 9.1% and
      the disease control rate (DCR) was 59.1%. The median progression-free survival
      (PFS) was 7.5 months, and the 6-month progression-free survival rate (PFR) was
      54.7%. Six patients died and the overall survival (OS) was not reached. AEs were
      controllable and all were in Grade 1-3. Conclusion: Apatinib mesylate tablets
      have a certain curative effect on patients with malignant melanomas of Stage IV
      who failed conventional chemotherapy. Apatinib mesylate tablets at a daily dose
      of 500 mg are well tolerated by most patients.

PMID- 30214240
TI  - Lymphangioleiomyomatosis: a case report and review of diagnosis and treatment.
AB  - Lymphangioleiomyomatosis (LAM) is a rare disease that generally affects young
      women and involves the abnormal proliferation of smooth muscle-like cells (LAM
      cells) in the lungs (pulmonary LAM) and extrapulmonary sites (extrapulmonary
      LAM). This disease is rare in males. It is hard to distinguish between lung
      cancer and pulmonary LAM, especially during early stages. Herein, we present a
      case of a 66-year-old man with a small nodule in the right upper lobe that was
      first diagnosed as a lung malignancy using a chest CT scan. After a wedge
      dissection, a pathologist performed a histologic and immunohistochemical
      examination, and a diagnosis of pulmonary LAM was made. We further performed a
      518-gene panel analysis using next-generation sequencing, and only three genes,
      BARD1, BLM, and BRCA2, were found to have mutations. We also provide a summary of
      the diagnosis and treatment of this disease.

PMID- 30214241
TI  - Genome-wide profiling reveals cancer-related genes with switched alternative
      polyadenylation sites in colorectal cancer.
AB  - Background: Alternative polyadenylation (APA) is an important post
      transcriptional regulation in eukaryotic cells. It plays considerable roles in
      many biological processes and diseases, such as cell differentiation,
      proliferation and cancer. Colorectal cancer (CRC) is one of the most common
      malignancies worldwide, which is among the top five in incidence and mortality of
      all cancers in China. Although there have been some studies on the APA of CRC,
      the normal and carcinoma samples used for genome-wide profiling were not matched.
      The purpose of this study was to obtain genes with switched 3'-untranslated
      region (UTR) that may be associated with intracellular regulation of CRC by
      analyzing APA patterns of strict control groups from clinical patients. Materials
      and methods: CRC and matched normal tissues were acquired from surgical specimens
      from three CRC patients. Their libraries of 3'-terminal fragments of mRNA with
      poly(A) tails were constructed by 3T-seq technology and sequenced by Illumina
      Hiseq X Ten. APA patterns of cancer and matched normal tissues were analyzed by
      bioinformatics analysis, and a representative gene, GPI, was verified by
      quantitative reverse transcription PCR. Results: Overall, we identified 35,076
      poly(A) sites in total. Compared to the matched normal tissues, we detected 350,
      405 and 375 genes with significantly APA-mediated 3'-UTR alteration in cancer
      tissues of three patients, respectively. Forty-seven genes with switched 3'-UTR
      were shared in all three patients. In addition, most of these genes have
      shortened 3'-UTRs, some of which were associated with cancers, such as GPI.
      Conclusion: Our studies found several genes with switched 3'-UTR in CRC patients,
      which may provide some important clues for more in-depth study of the cellular
      regulation in CRC from the perspective of post-transcriptional regulation. It may
      also help in the search for new biomarkers of CRC.

PMID- 30214242
TI  - SRPK1 is a poor prognostic indicator and a novel potential therapeutic target for
      human colorectal cancer.
AB  - Background: Serine/arginine protein kinase 1 (SRPK1) is a protein kinase that
      belongs to the serine/arginine-rich domain family of splicing factors which are
      essential for splice-site selection, especially the modulation for RNA
      metabolism, localization, and translation. High expression of SRPK1 has been
      found in numerous human cancers, but its mechanism in colorectal cancer (CRC) is
      still rarely reported. Purpose: To investigate the expression of SRPK1 in CRC
      tissues and cells and determine its functions and mechanism in CRC. Methods: The
      expression of SRPK1 was explored in human CRC patients and cells by
      immunohistochemistry, real-time quantitative PCR, and Western blot; Cell Counting
      Kit-8, Transwell, flow cytometry, and tube formation assay were used to
      investigate the CRC cell viability, migration, apoptosis, and angiogenesis,
      respectively. Results: SRPK1 was overexpressed in CRC tumor tissues and cells,
      and correlated with tumor node metastasis stage; inhibition of SRPK1 by siRNA
      resulted in decreased cell growth and migration, significantly increased
      apoptosis, and suppressed angiogenesis. Conclusion: SRPK1 can be a prognostic
      indicator of CRC and may be a therapeutic target for CRC.

PMID- 30214243
TI  - STARD13 is positively correlated with good prognosis and enhances 5-FU
      sensitivity via suppressing cancer stemness in hepatocellular carcinoma cells.
AB  - Background: STARD13 has been revealed to suppress tumor progression. However, the
      roles in regulating the stemness of hepatocellular carcinoma (HCC) cells are
      unclear. Methods: Quantitative real-time PCR (qRT-PCR) was used to detect STARD13
      expression in HCC tissues and normal adjacent tissues. Kaplan Meier (KM)-plotter
      analysis was performed to analyze the correlation between STARD13 expression and
      overall survival of HCC patients. Cell spheroid formation and ALDH1 activity
      analysis were carried out to detect the effects of STARD13 on the stemness of HCC
      cells. Furthermore, immunofluorescent, luciferase reporter, RhoA GTPase and F
      actin visualization assays were performed to explore the mechanisms contributing
      to STARD13-mediated effects. Results: STARD13 expression was significantly
      downregulated in HCC tissues compared with normal adjacent tissues, and was
      positively correlated with the overall survival of HCC patients. Functionally,
      overexpression of STARD13 inhibited cells stemness and enhanced 5-FU sensitivity
      in HCC cells. Mechanistically, STRAD13 overexpression suppressed RhoGTPase
      signaling and thus inhibited transcriptional factor YAP translocation from
      nuclear to cytoplasm, leading to the downregulation of transcriptional activity
      of YAP. Notably, the inhibitory effects of STARD13 on HCC cells stemness and 5-FU
      sensitivity were rescued by RhoA or YAP-5SA overexpression. Conclusion: Our
      results indicate that STARD13 could enhances 5-FU sensitivity by suppressing
      cancer stemness in hepatocellular carcinoma cells via attenuating YAP
      transcriptional activity.

PMID- 30214244
TI  - Successful cisplatin-etoposide chemotherapy-based treatment of a primary small
      cell neuroendocrine carcinoma of the tonsil with multiple metastases: a case
      report.
AB  - Extrapulmonary small cell neuroendocrine carcinoma (SNEC) is an extremely rare
      and highly malignant tumor with a poor prognosis. Multiple metastases of SNEC are
      even more rare, and patients with locally advanced and metastatic disease
      generally face a poor outcome. To date, only a few cases of SNEC have been
      reported. Here, we describe a rare case of a 70-year-old female patient with SNEC
      of the tonsil who presented with multiple metastases and had achieved a complete
      response (CR) of the primary lesion and cervical lymph nodes for more than 1 year
      after receiving palliative chemotherapy. Initially, the patient presented with a
      2-month history of throat pain. Magnetic resonance imaging and computed
      tomography revealed a soft mass with moderate enhancement on the left tonsil,
      which was confirmed by incisional aspiration biopsy. She was additionally sent
      for a positron emission tomography scan to evaluate small metastases in the left
      cervical lymph node, right lung, multiple mediastinal lymph nodes, and the fourth
      lumbar (L4) vertebra body metastases. Histopathological examination of the SNEC
      confirmed a nested, typical endocrine appearance with small round cells
      containing ovoid-shaped nuclei and high mitotic activity. Immunohistochemically,
      the tumor cells were positive for cytokeratin 8/18+, synaptophysin+, CD56+, and
      Ki-67 (<50%). The patient received 6 cycles of cisplatin combined with etoposide
      and was subsequently placed under close observation (<12 months). To date, she
      has achieved a CR of the primary lesion and cervical lymph nodes. In summary, we
      have described a case of successful treatment after chemotherapy for SNEC and
      have elucidated professional knowledge regarding the relevant aspects of SNEC.

PMID- 30214245
TI  - RGD-modified nanoliposomes containing quercetin for lung cancer targeted
      treatment.
AB  - Purpose: The aim of this study was to prepare RGD-modified nanoliposomes
      containing quercetin (QCT) distearoyl-L-a-phosphatidylethanolamine-polyethylene
      glycol 2000-RGD-liposomes ([DSPE]-PEG2000-RGD-LPs/QCT) for lung cancer targeting
      treatment. Methods: The physicochemical parameters of (DSPE)-PEG2000-RGD-LPs/QCT
      were characterized in terms of the particle size, zeta potential, morphology,
      entrapment efficiency, drug loading, and in vitro release behavior. In vivo,
      pharmacokinetics and antitumor studies of prepared formulations were also
      evaluated. Results: In this study, QCT was found to be easily dispersed in lipid
      solution and entrapped by the thin-film hydration method. The encapsulation ratio
      and drug loading of prepared LPs were 89.2%+/-7.4% and 9.2%+/-1.3% and the mean
      diameter was 93.4+/-7.2 nm from 3 batches. The results of in vitro experiments
      showed that the particle size of liposomes was suitable for the fenestrated
      vasculatures of cancer tissues via the enhanced permeability retention effect. In
      vitro, a relatively slow QCT release profile was observed in (DSPE)-PEG2000-RGD
      LPs, and the release mechanism fit with the Higuchi equation better. In vivo
      imaging results indicated that RGD-modified LPs had very good tumor targeting
      ability. (DSPE)-PEG2000-RGD-LPs/QCT showed a significant antitumor activity in
      mice with A549 tumors. Conclusion: Through this study, it was found that the RGD
      modified LPs loaded with QCT could potentially be a very promising lung-targeted
      preparation.

PMID- 30214246
TI  - Postoperative adjuvant chemo (embolization) therapy for hepatocellular carcinoma
      with portal vein tumor thrombosis.
AB  - Background: The present meta-analysis was aimed to evaluate the effects of
      postoperative adjuvant chemotherapy/transarterial chemoembolization (TACE) on the
      survival/disease-free survival (DFS) rate in hepatocellular carcinoma (HCC)
      patients with portal vein tumor thrombosis (PVTT). Methods: The relevant trials
      were collected using a database search of MEDLINE, Embase, Cochrane Library, Web
      of Science, ScienceDirect, the China Journal Full-text Database, and the National
      Institute of Health Clinical Trials Database. The 1-, 3-, and 5-year survival/DFS
      rates were considered to be the primary end points. A sensitivity analysis was
      conducted by reanalyzing the data using different statistical approaches.
      Results: Eight studies met the inclusion criteria. When compared with surgery
      alone, the pooled OR showed that the postoperative adjuvant therapy significantly
      increased the 1-, 3-, and 5-year survival rates for HCC patients with PVTT (the
      pooled OR and 95% CI of the 1-, 3-, and 5-year survival rates, respectively, were
      as follows: 2.72, 1.98-3.74; 1.62, 1.13-2.33; 1.99, 1.20-3.29). In addition, when
      compared with surgery alone, subgroup analysis showed that the postoperative
      chemotherapy improved the 1-, 3-, and 5-year survival rates of HCC patients with
      PVTT. Conclusion: Compared with surgery alone, postoperative adjuvant
      chemotherapy can improve the 1-, 3- and 5-year survival rates of HCC patients
      with PVTT. However, postoperative TACE can only increase the 1-year survival
      rate. However, due to the limitations of this meta-analysis, additional relevant
      trials are required to confirm these findings.

PMID- 30214247
TI  - Adverse outcomes from initiation of systemic corticosteroids for asthma: long
      term observational study.
AB  - Purpose: Prior work suggests a threshold of four courses/year of systemic
      corticosteroid (SCS) therapy is associated with adverse consequences. The
      objective of this study was to investigate the onset of adverse outcomes
      beginning at SCS initiation in a broad asthma population. Patients and methods:
      This historical matched cohort study utilized anonymized, longitudinal medical
      record data (1984-2017) of patients (>=18 years) with active asthma. Matched
      patients with first SCS prescription (SCS arm) and no SCS exposure (non-SCS arm)
      were followed until first outcome event. Associations between time-varying
      exposure measures and onset of 17 SCS-associated adverse outcomes were estimated
      using Cox proportional hazard regression, adjusting for confounders, in separate
      models. Results: We matched 24,117 pairs of patients with median record
      availability before SCS initiation of 9.9 and 8.7 years and median follow-up 7.4
      and 6.4 years in SCS and non-SCS arms, respectively. Compared with patients in
      the non-SCS arm, patients prescribed SCS had significantly increased risk of
      osteoporosis/osteoporotic fracture (adjusted hazard ratio 3.11; 95% CI 1.87
      5.19), pneumonia (2.68; 2.30-3.11), cardio-/cerebrovascular diseases (1.53; 1.36
      1.72), cataract (1.50; 1.31-1.73), sleep apnea (1.40; 1.04-1.86), renal
      impairment (1.36; 1.26-1.47), depression/anxiety (1.31; 1.21-1.41), type 2
      diabetes (1.26; 1.15-1.37), and weight gain (1.14; 1.10-1.18). A dose-response
      relationship for cumulative SCS exposure with most adverse outcomes began at
      cumulative exposures of 1.0-<2.5 g and for some outcomes at cumulative exposures
      of only 0.5-<1 g (vs >0-<0.5 g reference), equivalent to four lifetime SCS
      courses. Conclusion: Our findings suggest urgent need for reappraisal of when
      patients need specialist care and consideration of nonsteroid therapy.

PMID- 30214248
TI  - School-based supervised therapy programs to improve asthma outcomes: current
      perspectives.
AB  - Background: Asthma is one of the most common chronic diseases of childhood
      affecting 6.2 million (8.4%) children (<18 years old) in the USA. Asthma is also
      a leading cause of school absenteeism. Daily administration of preventive asthma
      medications improves asthma control. However, poor medication adherence is one of
      the barriers in achieving improved asthma outcomes. School-based supervised
      asthma therapy programs have been implemented to address this barrier.
      Objectives: To conduct a review of the literature on school-based supervised
      asthma therapy interventions and the effect on outcomes in children with
      persistent asthma. Methods: We conducted a literature search using electronic
      search engines (ie, PubMed and Cochrane) and combinations of different search
      terms "school-based asthma," "school-based asthma therapy," and "school-based
      supervised asthma therapy." Inclusion criteria were school-based interventions
      with supervised asthma medication administration conducted in the USA, measuring
      asthma outcomes. From 443 titles and abstracts, 9 studies met the inclusion
      criteria. Results: School-based interventions with supervised asthma medication
      administration revealed improvement in asthma outcomes, including improved
      medication adherence, increased symptom-free days, decreased daytime and
      nighttime symptoms, decreased use of rescue medication, decreased asthma-related
      health care utilization, fewer exacerbations requiring treatment with prednisone,
      decreased school absenteeism due to asthma, fewer days of activity limitation,
      improved quality of life, and improvement in both pulmonary inflammatory markers
      and peak flow readings. Conclusion: Our literature review demonstrated that
      school-based supervised asthma therapy improves asthma outcomes in urban children
      with persistent asthma. Schools are an ideal setting for implementation of asthma
      interventions for children and adolescents.

PMID- 30214249
TI  - Characteristics of patients with severe, uncontrolled, eosinophilic asthma
      enrolled in a French cohort.
AB  - Background and objective: Benralizumab (FasenraTM) has recently been approved as
      add-on maintenance treatment for adult patients with severe eosinophilic asthma
      inadequately controlled despite high-dosage inhaled corticosteroids plus long
      acting beta2-agonists. We aimed to identify and describe the clinical
      characteristics and disease burden of patients with severe, uncontrolled,
      eosinophilic asthma in France who may be eligible for treatment with
      benralizumab. Patients and methods: This was a retrospective analysis of a
      prospective, noninterventional, observational study of patients in France
      enrolled in the Asthma and Bronchial Obstruction Cohort (COBRA). First, we
      selected adult patients with severe asthma, a documented blood eosinophil count,
      12 months of baseline data, and 12 months of follow-up data. Of these study
      eligible patients, we next determined the prevalence and described the clinical
      characteristics and disease burden of patients who would be eligible to receive
      benralizumab, namely those with >=2 asthma exacerbations in the previous 12
      months and a blood eosinophil count >=300/MUL who were receiving high-dosage
      inhaled corticosteroids/long-acting beta2-agonists. Results: Of the 441 patients
      eligible for this study, 85 (19%) met the criteria for benralizumab therapy. At
      study inclusion, benralizumab-eligible patients had a smaller prebronchodilator
      forced expiratory volume in 1 second and less effective asthma control compared
      with benralizumab-ineligible patients. During the 12-month follow-up period,
      benralizumab-eligible patients had greater frequencies of asthma exacerbations
      and hospitalizations compared with benralizumab-ineligible patients. Conclusion:
      Of patients with severe asthma, approximately 20% were qualified for benralizumab
      treatment. Benralizumab-eligible patients had increased bronchial obstruction,
      worse asthma control, and a greater frequency of asthma exacerbations and
      hospitalizations during follow-up care compared with benralizumab-ineligible
      patients, demonstrating inadequate disease control for these patients.

PMID- 30214250
TI  - Rupatadine oral solution for 2-5-year-old children with allergic rhinitis: a
      safety, open-label, prospective study.
AB  - Background: There are few clinical trials that assess the efficacy of
      antihistamines in very young children. Rupatadine is a second-generation
      antihistamine indicated for the treatment of allergic rhinitis (AR) and
      urticaria. In this study, AR symptoms were evaluated before and after daily 1
      mg/mL rupatadine oral solution administration in 2-5-year-old children. Methods:
      A multicenter open-label study was carried out in 2-5-year-old children with AR.
      Safety assessments were collected during the study including spontaneous adverse
      events, vital signs, and electrocardiogram (QTc interval). Additionally,
      evaluations of Total Five Symptoms Score (T5SS, including: nasal congestion;
      sneezing; rhinorrhoea; itchy nose, mouth, throat, and/or ears; and itchy, watery,
      and red eyes) were analyzed. Symptoms were evaluated by parents/legal guardian
      before and after 4 weeks of rupatadine administration, dosed according to body
      weight. Results: A total of 44 children received the study treatment. Only 15
      adverse events were reported. All of them were of mild intensity and considered
      not related to the study treatment. No patient exceeded the standard parameter of
      >450 ms in the last visit, for the QTc interval on their electrocardiograms. From
      a maximum score value of 15, T5SS values at Day 14 (6.35) and Day 28 (5.42) were
      both statistically significant different (p<0.001) from the baseline T5SS value
      (mean 8.65), with a reduction of 26.6% and 37.4%, respectively. All individual
      symptoms, including nasal congestion, showed also a decrease from baseline at
      both 14 and 28 days. Conclusion: Rupatadine 1 mg/mL oral solution was found to be
      safe in 2-5-year-old children, correlating with an improvement of AR symptoms,
      overall and each individually, after a daily dose administration. With this
      study, we enlarge the available information in this very young pediatric
      patients' group, in which there is a general lack of clinical evidence.

PMID- 30214251
TI  - Susceptibility to ceftobiprole of respiratory-tract pathogens collected in the
      United Kingdom and Ireland during 2014-2015.
AB  - Purpose: Lower respiratory tract infections (LRTIs) can cause significant
      morbidity and mortality and are becoming increasingly difficult to treat because
      of the growing prevalence of resistance to conventional antimicrobial agents.
      This study aimed to assess the current in vitro susceptibility of respiratory
      tract pathogens collected from the UK and Ireland to ceftobiprole, an advanced
      generation cephalosporin, as compared with other antibiotics. Methods: Pathogens
      isolated from patients with LRTIs were analyzed as part of the British Society
      for Antimicrobial Chemotherapy Antimicrobial Resistance Surveillance Programme
      during 2014-2015. Antibiotic susceptibility was evaluated using European
      Committee on Antimicrobial Susceptibility Testing breakpoints, including the
      ceftobiprole pharmacokinetic/pharmacodynamic non-species-specific breakpoint when
      species-specific breakpoints were not available. Results: One thousand one
      hundred and sixty-eight isolates from community-onset LRTIs and 1,264 isolates
      from hospital-onset LRTIs were analyzed. The ceftobiprole susceptibility rate was
      99.8% (428/429) for Streptococcus pneumoniae, 100% (502/502) for Haemophilus
      influenzae, and 99.6% (236/237) for Moraxella catarrhalis. All Staphylococcus
      aureus isolates, including methicillin-susceptible S. aureus (MSSA; N=181) and
      methicillin-resistant S. aureus (MRSA; N=35), were susceptible to ceftobiprole.
      Overall, ceftobiprole susceptibility was observed in 88.1% (215/244) of
      Escherichia coli isolates, 83.4% (156/187) of Klebsiella pneumoniae isolates and
      86.7% (98/113) of Enterobacter spp. isolates. Conclusion: Ceftobiprole had in
      vitro activity against all S. aureus (both MSSA and MRSA) isolates, and almost
      all S. pneumoniae isolates, as well as against Gram-negative bacteria associated
      with community-onset or hospital-onset LRTIs. Based on this analysis,
      ceftobiprole is a good treatment option when broad-spectrum antibiotic coverage
      is needed for LRTIs.

PMID- 30214252
TI  - The changes of expressive levels of IL-17A, STAT3, and RORgammat in different
      invasive pulmonary aspergillosis mice.
AB  - Background: T helper 17 (Th17) lymphocytes play an important role in Aspergillus
      adaptive immune response against Aspergillus fumigatus, but there is little
      attention focused on the different types of immunosuppressive models in which
      invasive pulmonary aspergillosis (IPA) develops. In addition, the expression
      levels of signal transducer and activator of transcription 3 (STAT3)/retinoic
      acid-related orphan nuclear receptor gamma (RORgammat)/interleukin (IL)-17A
      signaling pathway, which is involved in the regulation of Th17 cells, as well as
      whether there are differences between two types of IPA mice models, remain
      unknown. Materials and methods: Six to eight weeks old female BALB/c mice were
      treated with cortisone acetate or cyclophosphamide to establish the
      immunosuppressive mice models, and then, A. fumigatus inoculum was injected to
      form the IPA groups and sterile saline was injected to form the control groups.
      Flow cytometry was performed to measure the proportion of Th17 cells in CD4+ T
      cells in the peripheral blood, spleen, and lung of the mice. The expression of IL
      17A, RORgammat, and STAT3 mRNA was detected by real-time polymerase chain
      reaction. Concentrations of IL-6 in the plasma and bronchoalveolar lavage fluid
      were measured by enzyme-linked immunosorbent assay. Results: The proportion of
      Th17 in the peripheral blood and lung tissue in neutropenic IPA mice showed a
      more significant increase than in non-neutropenic IPA mice (P<0.01). The IL-6
      protein also showed the same trend in plasma and bronchoalveolar lavage fluid
      (P<0.01). Compared with the control groups, the expression of IL-17A at mRNA
      level in the lung was significantly increased, while RORgammat/STAT3 mRNA was
      significantly decreased in the IPA groups (P<0.01). Conclusion: The expression of
      RORgammat and STAT3 mRNA in the lung tissue in both groups was significantly
      decreased. IL-17 may play a negative role in the defense against Aspergillus
      through uprating IL-6.

PMID- 30214254
TI  - Epidemiology of and risk factors for infection with extended-spectrum beta
      lactamase-producing carbapenem-resistant Enterobacteriaceae: results of a double
      case-control study.
AB  - Purpose: Carbapenem-resistant Enterobacteriaceae (CRE) have been increasingly
      reported worldwide and pose a serious public threat, but the clinical
      significance of extended-spectrum beta-lactamase (ESBL) production in CRE is not
      well established. Patients and methods: A retrospective case-case-control study
      was conducted to identify the clinical characteristics of patients with ESBL-CRE.
      The susceptibility of isolates obtained from these patients was assessed. The
      detection of ESBL and carbapenemase-related genes was performed by PCR methods.
      Predictors of 30-day mortality in patients with ESBL-CRE infection were also
      identified in our study. Results: A total of 149 patients with CRE infection
      caused by Enterobacter cloacae (n=74), Escherichia coli (n=38), and Klebsiella
      pneumoniae (n=37) were identified in Chongqing, Southwestern China, between
      January 2011 and December 2014. Of the 35 isolates detected with carbapenemase
      related genes, 16 isolates had New Delhi metallo-beta-lactamase (NDM), nine
      isolates had K. pneumoniae carbapenemase (KPC), seven isolates had imipenemase
      (IMP), and four isolates had oxacillinase (OXA)-1. One strain of enterobacter
      cloacae carried both NDM-1 and IMP-8 genes. ESBL isolates included the genes CTX
      M (72/149), SHV (64/149), and TEM (54/149). All ESBL-CRE isolates exhibited
      ertapenem resistance, and the rate of cephalosporin resistance was relatively
      high in general. Independent risk factors for infection with ESBL-CRE included
      previous exposure to beta-lactam antibiotics, transfer from another hospital, and
      some underlying diseases. In addition, solid tumors, hypoalbuminemia, and central
      venous catheters were independent predictors of mortality in patients with ESBL
      CRE infection. Conclusion: Physicians should understand the peculiar predictors
      for the identification of these organisms among high-risk patients.

PMID- 30214253
TI  - Prevalence of Plasmodium falciparum antimalarial drug resistance genes in
      Southeastern Gabon from 2011 to 2014.
AB  - Purpose: The introduction of artemisinin-based combination therapies (ACTs) in
      treating uncomplicated malaria and sulfadoxine-pyrimethamine (SP) as intermittent
      preventive treatment during pregnancy drastically decreased the burden of
      malarial disease around the world. However, ACTs are known to select for drug
      resistance markers. In Gabon, artemether-lumefantrine induced an increase in the
      prevalence of N86-Pfmdr1, which is associated with treatment failure. However,
      little data are available regarding resistance markers in Southeastern Gabon.
      This study aimed to evaluate the evolution of resistance haplotypes in the Pfcrt,
      Pfdhps, Pfdhfr, and PfK13 genes from 2011 to 2014 in Southeastern Gabon. Methods:
      A total of 233 Plasmodium falciparum DNA samples were collected from febrile
      pediatric patients in South Gabon: Franceville, an urban area; Koulamoutou, a
      semi-urban area; and Lastourville, a rural area. Pfcrt, Pfdhps, Pfdhfr, and the
      propeller domain of PfK13 were sequenced for all isolates. Results: The overall
      prevalence (3.7%-11.5%) of the wild-type haplotype Pfcrt 72-76 CVMNK was not
      significantly different between 2011 and 2014 in Southeast Gabon. For Pfdhfr
      (codons 51, 59, 108, 164), the IRNI triple-mutant haplotype was the most
      prevalent (>89.0%). The ICNI and NCNI mutant haplotypes and the NCSI wild-type
      haplotype showed a minor prevalence. There were no differences in the
      distributions of these haplotypes across the 4 years and the three study sites.
      For Pfdhps, the AAKAA and SGKAA mutant haplotypes and the SAKAA wild-type
      haplotype were similarly present in the three areas during the study period. The
      AGKAA double mutant was first observed in 2013 in Franceville and in 2014 in
      Koulamoutou and Lastourville. Interestingly, only the A578S mutation (0.4%) and
      two new A494V (0.4%) and V504A (0.9%) mutations were found in PfK13. Conclusion:
      Despite the withdrawal of chloroquine, the frequency of the resistant allele 76T
      remained high in the south of Gabon. Moreover, a high level of resistant
      haplotypes against IPTp-SP was found.

PMID- 30214255
TI  - Comparison of five commonly used automated susceptibility testing methods for
      accuracy in the China Antimicrobial Resistance Surveillance System (CARSS)
      hospitals.
AB  - Objective: The objective of this study was to evaluate the performance of five
      commonly used automated antimicrobial susceptibility testing (AST) systems in
      China (Vitek 2, Phoenix, Microscan, TDR, and DL). Materials and methods: Two
      "unknown" isolates, S1 (ESBL-producing Escherichia coli) and S2 (KPC-producing
      Klebsiella pneumoniae), were sent to 886 hospitals in China for identification
      and AST. Using broth microdilution method (BMD) as gold standard, minimum
      inhibitory concentrations (MICs) were determined. Results: Most hospitals (392,
      46.1%) used Vitek 2, followed by 16% each for Phoenix, Microscan, and DL systems,
      and 5.9% (50) used TDR system. MICs of 22 antimicrobials were evaluated for two
      study isolates plus three ATCC strains. Individual susceptibility results for
      three ATCC strains (n=1581) were submitted by 780 (91.2%) hospitals. For each AST
      system, 8.7% (6/69) to 13.0% (33/253) reported MICs outside the expected range
      for several drugs. For the two study isolates, TDR and DL systems performed the
      worst in MIC determination and susceptibility categorization of cefazolin and
      cefepime, while the Microscan system had difficulties in susceptibility
      categorization for aztreonam and ertapenem. Categorical agreements were >90% for
      most antimicrobials tested for both the isolates, among which, using BMD, no
      essential agreements were noted for ampicillin, piperacillin, cefazolin,
      cefuroxime, ceftriaxone, and trimethoprim/sulfamethoxazole. All AST systems
      except Vitek 2 showed unacceptable VMEs for cefazolin (S1 and S2) and major
      errors for ceftazidime, cefepime, and aztreonam (isolate S1), while Vitek 2
      showed a high VME rate for cefepime (10.0%) and meropenem (6.2%) for S2.
      Conclusion: None of the five automated systems met the criteria for acceptable
      AST performance, but Vitek 2 provided a relatively accurate and conservative
      performance for most of the antimicrobials.

PMID- 30214256
TI  - Management and outcome of bloodstream infections: a prospective survey in 121
      French hospitals (SPA-BACT survey).
AB  - Background: Bloodstream infections (BSIs) are severe infections that can be
      community or hospital acquired. Effects of time to appropriate treatment and
      impact of antimicrobial management team are discussed in terms of outcome of BSI.
      We sought to evaluate the impact of initial BSI management on short-term
      mortality. Patients and methods: A prospective, multicenter survey was conducted
      in 121 French hospitals. Participants declaring BSI during a 1-month period were
      included consecutively. Data on patient comorbidities, illness severity, BSI
      management, and resistance profile of bacterial strains were collected.
      Predictors of 10-day mortality were identified by multivariate regression for
      overall BSI, health care-related and hospital-acquired BSI. Results: We included
      1,952 BSIs. More than a third of them were hospital acquired (39%). Multidrug
      resistance was identified in 10% of cases, mainly in health care-related BSI.
      Empirical therapy and targeted therapy were appropriate for 61% and 94% of cases,
      respectively. Increased 10-day mortality was associated with severe sepsis,
      septic shock, increasing age, and any focus other than the urinary tract.
      Decreased mortality was associated with receiving at least one active antibiotic
      within the first 48 hours. Intervention of antimicrobial management team during
      the acute phase of BSI was associated with a decreased mortality at day 10 in the
      overall population and in health care-related BSI. Conclusion: Optimizing BSI
      management by increasing rapidity of appropriate treatment initiation may
      decrease short-term mortality, even in countries with low rate of multidrug
      resistant organisms. Early intervention of antimicrobial management team is
      crucial in terms of mortality.

PMID- 30214257
TI  - Efficacy of intraventricular amikacin treatment in pan-resistant Pseudomonas
      aeruginosa postsurgical meningitis.
AB  - Background: We describe a case of pan-resistant Pseudomonas aeruginosa
      postsurgical meningitis associated with the presence of an external ventricular
      device. We changed therapy twice; finally, by using amikacin and a continuous
      infusion of cefepime, we obtained clinical improvement. Case presentation: A
      female patient, who underwent surgery for a cavernous angioma, presented with
      meningitis. Cerebrospinal fluid culture revealed a multidrug-resistant
      Pseudomonas aeruginosa, initially sensitive only to colistin. We successfully
      used intrathecal amikacin and intravenous cefepime continuous infusion plus
      intravenous amikacin after two previous ineffective therapeutic approaches.
      Conclusion: The evaluation of the antibiotic concentration and the bactericidal
      activity in cerebrospinal fluid may contribute to the choice of the drug in cases
      of multidrug-resistant meningitis.

PMID- 30214258
TI  - Benchmarking for surgical site infections among gastrointestinal surgeries and
      related risk factors: multicenter study in Kuwait.
AB  - Purpose: To measure surgical site infection (SSI) rates among gastrointestinal
      surgeries and to identify the associated risk factors. Patients and methods: We
      conducted a multicenter, retrospective, surveillance-based study of adults
      undergoing gastric, colon, and small bowel (SB) procedures from January to
      December 2016. Univariate and multivariate analyses were conducted to determine
      the predictive variables in each surgery. Results: In total, 71 of 2,099 patients
      developed SSI - 0.8%, 19.8%, and 10.8% following gastric, colon, and SB
      surgeries, respectively. In gastric surgery, the risk factors identified by
      univariate analysis were age, duration, wound class, risk index, emergency, and
      scope use (P<0.05). Logistic regression analysis revealed that the laparoscopic
      approach was the only significant predictor, with an inverse relationship of SSI
      rate vs open gastric surgery (P<0.05). Prolonged duration was a significant risk
      factor for developing SSI in colon surgery, and emergency was a significant risk
      for development of SSI in SB surgery. Gram-negative bacilli were the main
      causative pathogens, with a high percentage of multidrug-resistant organisms.
      Conclusion: Variances in SSI rates and risk factors among gastric, colon, and SB
      surgery were detected. The use of an endoscope in gastric surgeries exhibited a
      protective effect against the development of SSI. The reduction of the SSI rate
      can be achieved by targeted preventive interventions for the identified risk
      factors.

PMID- 30214259
TI  - In vivo antimicrobial activity of the hybrid peptide H4: a follow-up study.
AB  - Background: The consistent upsurge in antimicrobial resistance globally is
      threatening the world population with the prospect of facing the post-antibiotic
      era. Dry pipelines and a drastic decrease of antimicrobial drug development
      accompany this rise in antimicrobial resistance. Governments and health
      authorities are calling for the development of novel classes of antimicrobial
      agents that would tackle this problem. Antimicrobial peptides represent a
      promising group of molecules for antimicrobial drug development due to their
      potency and rapid mode of killing. However, several obstacles, such as high
      mammalian cell toxicity and lack of target selectivity, have challenged the
      development of such agents. Methods: We have recently designed a novel hybrid
      peptide named H4 that exhibits potent antimicrobial activity and low toxicity in
      vitro. In order to confirm the potential therapeutic efficacy and safety of the
      peptide, we evaluated the in vivo activity and toxicity of H4 against
      Staphylococcus aureus peritonitis mice model. Results: Our results indicate that
      H4 is highly potent in eradicating bacterial infections in vivo with an effective
      dose50 value of 4.55+/-0.89 mg/kg. Additionally, the acute systemic toxicity
      results indicate that the peptide exhibits a high therapeutic index with no
      significant negative effects on the function of major body organs. Conclusion: H4
      is a novel hybrid peptide with great potential for antimicrobial drug
      development.

PMID- 30214260
TI  - Overview of pneumococcal serotypes and genotypes causing diseases in patients
      with chronic obstructive pulmonary disease in a Spanish hospital between 2013 and
      2016.
AB  - Background: Streptococcus pneumoniae is an important pathogen in chronic
      obstructive pulmonary disease (COPD). We aimed at showing the recent changes in
      the epidemiology of pneumococcal diseases in patients with COPD, especially after
      the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13).
      Methods: From 2013 to 2016, strains causing invasive pneumococcal disease (IPD),
      non-bacteremic pneumococcal pneumonia (non-BPP), and acute exacerbation of COPD
      (AE-COPD) were prospectively included. Antimicrobial susceptibility testing,
      serotyping, and genotyping were analyzed. Results: We collected 345 pneumococci
      from 286 COPD patients (57 IPD, 78 non-BPP, and 210 AE-COPD). The most frequent
      serotypes were serotypes 3 (14.0%), 8 (14.0%), and 12F (8.8%) in IPD; serotypes 3
      (16.7%), 11A (9%), 9L/N (7.7%), and 23A (7.7%) in non-BPP; and serotypes 11A
      (11%), nontypeable (11%), and 6C (10%) in AE-COPD. Resistance rates were highest
      among AE-COPD strains. Penicillin resistance was associated with serotypes 11A
      (CC156) and 19A (CC320 and CC230). Compared with previous studies,
      fluoroquinolone resistance in AE-COPD increased (9.5%), PCV13 serotypes decreased
      (31.6%, 26.9%, and 16.7% for IPD, non-BPP, and AE-COPD, respectively), and
      serotype 11A-CC156 in AE-COPD and serotype 8 in IPD increased. Conclusion: The
      epidemiology of pneumococcal disease in COPD changed after the introduction of
      PCV13 in children. Increases in the highly invasive serotype 8 among patients
      with IPD and in serotype 11A-CC156 among patients with AE-COPD could compromise
      the ability of current PCVs to prevent diseases. Vaccines with a greater coverage
      could improve the benefits of adult vaccination.

PMID- 30214261
TI  - Budget impact model of secukinumab for the treatment of moderate-to-severe
      psoriasis, psoriatic arthritis, and ankylosing spondylitis in Italy: a cross
      indication initiative.
AB  - Objective: Secukinumab, a fully human monoclonal IgG1 antibody that selectively
      neutralizes the proinflammatory cytokine IL-17A, has been approved in Europe in
      2015 for the treatment of adult patients with moderate-to-severe plaque
      psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This
      analysis assessed the budget impact of introduction of secukinumab to the Italian
      market for all three indications from the perspective of the Italian National
      Health Service. Materials and methods: A cross-indication budget impact model was
      developed and included biologic-treated adult patients diagnosed with psoriasis,
      PsA, and AS. The analyses were conducted over a 3-year time horizon and included
      direct costs (drug therapy costs, administration costs, diseases-related costs,
      and adverse events costs). Model input parameters (epidemiology, market share
      projections, resource use, and costs) were obtained from the published literature
      and other Italian sources. The robustness of the results was tested via one-way
      sensitivity analyses: secukinumab cost, secukinumab market share, intravenous
      administration costs, and adverse events costs were varied by +/-10%. Results:
      The total patient population for secukinumab over the 3-year timeframe was
      projected to be 6,648 in the first year, increasing to 12,001 in the third year,
      for all three indications combined (psoriasis, PsA, and AS). Compared to a
      scenario without secukinumab in the market, the introduction of secukinumab in
      the market for the treatment of psoriasis, PsA, and AS showed a cumulative 3-year
      incremental budget impact of -5%, corresponding to savings of ?66.1 million and
      per patient savings of about ?1,855. The majority of the cost savings came from
      the adoption of secukinumab in AS (58%), followed by PsA (29%) and psoriasis
      (13%). Sensitivity analyses confirmed the robustness of the results. Conclusion:
      Results from this cross-indication budget impact model show that secukinumab is a
      cost-saving option for the treatment of PsA, AS, and psoriasis patients in Italy.

PMID- 30214262
TI  - Incidence of febrile neutropenia during chemotherapy among patients with
      nonmyeloid cancer receiving filgrastim vs a filgrastim biosimilar.
AB  - Background: Filgrastim and other granulocyte colony-stimulating factors are
      recommended to decrease febrile neutropenia (FN) incidence among patients with
      nonmyeloid cancers undergoing chemotherapy. Data comparing biosimilar filgrastim
      sndz with reference filgrastim (filgrastim-ref) are limited outside of clinical
      trials in the US. Objective: To compare the incidence of FN across chemotherapy
      cycles 1-6 between patients treated with filgrastim-sndz vs filgrastim-ref.
      Materials and methods: This was a retrospective claims analysis of patients with
      nonmyeloid cancer enrolled in commercial or Medicare Advantage plans from March
      2015 to June 2016 and receiving filgrastim-sndz or filgrastim-ref during >=1
      completed chemotherapy cycle. Patients undergoing hematopoietic stem cell
      transplantation, pregnant patients, and those with missing data were excluded. FN
      was identified using the diagnosis codes for neutropenia + fever, neutropenia +
      bacterial/fungal infection, and neutropenia + infection + fever. Equivalence
      testing for FN incidence at the cycle level across chemotherapy cycles 1-6 was
      conducted for filgrastim-sndz vs filgrastim-ref after adjusting for baseline
      characteristics using inverse probability of treatment weighting. Results were
      considered equivalent if the 90% CIs for between-cohort differences were within
      +/-6.0%. Results: The analysis included 3,459 patients (162 filgrastim-sndz and
      3,297 filgrastim-ref). Before weighting, the filgrastim-sndz cohort was younger
      than filgrastim-ref and had a higher proportion of men, a higher proportion with
      commercial insurance, and lower proportions with granulocyte colony-stimulating
      factor prophylaxis or metastatic cancer. After weighting, baseline
      characteristics were similar between cohorts. Adjusted FN incidence was
      equivalent for filgrastim-sndz vs filgrastim-ref, respectively: neutropenia +
      fever, 0.81% vs 0.61% (difference [90% CI]=0.20 [-0.57 to 1.56]); neutropenia +
      infection, 1.21% vs 1.33% (difference [90% CI]=-0.12 [-1.17 to 2.28]);
      neutropenia + infection + fever, 0.0% vs 0.14% (difference=-0.14; CI not
      calculated because filgrastim-sndz had 0 events). Conclusion: Filgrastim-sndz and
      filgrastim-ref are statistically equivalent for preventing FN across chemotherapy
      cycles 1-6 among patients with nonmyeloid cancer.

PMID- 30214263
TI  - Prevalence of diabetic comorbidities and knowledge and practices of foot care
      among diabetic patients: a cross-sectional study.
AB  - Background: Diabetes mellitus with comorbid complications constitute a major
      public health problem worldwide. The aim of this study was to evaluate the risk
      of comorbid complications with glycosylated hemoglobin levels and diabetes
      duration. Also assessed were patients' diabetic foot-care knowledge and
      practices. Patients and methods: This was a quasiexperimental study. A total of
      360 type 2 diabetes mellitus patients were interviewed at a government health
      care center in Riyadh, Saudi Arabia. Diabetic complications and HbA1c-level data
      were collected from hospital records. A standard questionnaire was used to assess
      their diabetic foot-care knowledge and practice. Results: Of the type 2 diabetes
      mellitus patients, 32.5% had highly uncontrolled glycosylated hemoglobin (HbA1c)
      levels (>=8.6%) and 62.8% had had diabetes >10 years. The patients had comorbid
      complications, such as hypertension (61.4%), dyslipidemia (58.6%), retinopathy
      (23.3%), heart disease (14.4%), and severe foot complications (3.9%). The
      majority of highly uncontrolled HbA1c-level patients had retinopathy (OR 8.90,
      P=0.0001), foot complications (OR 8.09, P=0.0001), dyslipidemia (OR 2.81,
      P=0.010), and hypertension (OR 2.0, P=0.028) compared to the controlled HbA1c
      level (<7%) group. Patients with diabetes >10 years also had higher prevalence of
      foot complications (OR 2.92, P=0.0001), retinopathy (OR 2.17, P=0.011), and
      hypertension (OR 1.67, P=0.033). From patient responses, physicians examined only
      34.2% of patient feet and 36.7% of patients received physicians advice for foot
      care. About 70% of patients had knowledge of diabetic foot care; however, only
      41.7% of patients always examined their feet, 41.4% washed feet with warm water,
      31.4% carefully dried between the toes, and 33.1% were using foot-moisturizing
      substances. Conclusion: The prevalence of comorbid complications was higher in
      the Saudi population compared to other international studies. Also, foot-care
      practice was not satisfactory. Therefore, there is need of improvement and
      increased awareness among physicians and patients to check regularly for proper
      care of the diabetic foot to avoid diabetic foot-related complications.

PMID- 30214264
TI  - Daily intake of Kaempferia parviflora extract decreases abdominal fat in
      overweight and preobese subjects: a randomized, double-blind, placebo-controlled
      clinical study.
AB  - Purpose: Obesity is a serious problem, which is now a worldwide health problem.
      Kaempferia parviflora extract (KPE) exhibits anti-obesity effects in animals.
      However, as no clinical trials have evaluated the anti-obesity effects of KPE in
      humans, we examined the effects of KPE in reducing abdominal fat in overweight
      and preobese Japanese subjects. Materials and methods: A 12-week, single-center,
      randomized, double-blind, placebo-controlled clinical trial was conducted.
      Seventy-six subjects (males and females aged 20 to <65 years) with a body mass
      index >=24 and <30 kg/m2 were randomly assigned into two groups. The subjects in
      each group ingested one capsule of placebo or active KPE (containing 150 mg of
      KPE) once daily for 12 weeks. The primary outcome was reduction in visceral fat
      area as determined by computed tomography scanning. The key secondary outcomes
      were reductions in subcutaneous fat area and total fat area. Subgroup analysis
      was also performed in healthy subjects without dyslipidemia, hypertension, or
      hyperglycemia. The safety of KPE ingestion was also evaluated. Results: Compared
      with the placebo group, the active KPE group exhibited significant reduction in
      abdominal fat area (visceral, subcutaneous, and total fat) and triglyceride
      levels after 12 weeks. Subgroup analyses demonstrated a significant reduction in
      abdominal fat area and triglyceride levels in healthy subjects compared with the
      placebo group after 12 weeks. Neither group exhibited adverse events related to
      the test foods or clinically relevant abnormal changes in physical, biochemical,
      or hematologic parameters, or in urinalysis results and medical interview.
      Conclusion: Daily ingestion of KPE safely reduces body fat, particularly
      abdominal fat, in Japanese overweight and preobese subjects.

PMID- 30214265
TI  - Efficacy of bariatric surgery in improving metabolic outcomes in patients with
      diabetes. A 24-month follow-up study from a single center in the UAE.
AB  - Background: Owing to its impact on weight loss, remission of diabetes mellitus
      and metabolic syndrome, bariatric surgery has offered hope for grossly obese
      individuals. In recent years, obesity has increased in the UAE and the use of
      bariatric surgery has increased in-line with this trend. However, data regarding
      bariatric surgery outcomes in diabetic Emirati people is scarce. Objective: To
      evaluate the effect of bariatric surgery in patients with diabetes mellitus.
      Methods: This is a retrospective analysis of diabetic patients treated with
      bariatric surgery with a minimal follow-up of 1 year and extended for some
      patients (21) to 2 years follow up. A total of 80 patients underwent bariatric
      surgery. Two surgical procedures were used; laparoscopic sleeve gastrectomy
      (n=53) or mini-gastric bypass between January 1, 2015, and July 20, 2017.
      Results: Mean baseline weight was 119.2+/-31.2 kg, this has significantly dropped
      to 100.1+/-23.1, 91.2+/-22.3, 82.3+/-17.5, and 81.3+/-15.3 kg at 3, 6, 12, and 24
      months respectively, and this change was statistically significant P<0.001 at
      each time point. Mean baseline HbA1c was 8.6% +/- 2.3% and this dropped
      significantly to 6.5+/-1.7, 5.9+/-1.2, 5.6+/-0.8, and 5.4+/-0.7 at 3, 6, 12, and
      24 months respectively (P<0.000). In 49 (61.3%) we considered fatty liver based
      on ultrasound features either with or without elevation in alanine
      aminotransferase (ALT). We noticed a significant decrease in ALT at 3, 6, and 12
      months after surgery. Furthermore, 11 patients (22.4%) showed sonographic
      features of improvement in fatty liver in addition to normalization of ALT.
      Conclusions: Bariatric surgery was effective over a follow-up period of 2 years
      in achieving significant weight loss as well as resulting in improvements in
      glycemic control, blood pressure, and fatty liver.

PMID- 30214266
TI  - Fecal microbiota transplant - a new frontier in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic multifactorial disease that affects
      the gastrointestinal tract and results from an aberrant immune response toward
      luminal antigens in genetically susceptible people. Most of the current therapies
      for IBD focus on the management of the inflammation by using corticosteroids,
      immune modulators, and more recently, monoclonal antibodies (biological therapy).
      Although these therapies provide benefit in most cases, there are still a
      significant number of patients who do not respond or become refractory over time,
      suggesting the need for alternative therapeutic options. In the last decade, it
      has been recognized that "dysbiosis," an imbalanced gut microbiota, is a key
      element in IBD suggesting microbiome-based therapies as an attractive approach.
      Recently, fecal microbiota transplant (FMT) has been successfully used for the
      treatment of Clostridium difficile infection, and it is now under investigation
      for the treatment of IBD. Clinical trials data are still poor but strongly
      support a future introduction of FMT in therapy to manage IBD microbiome. More
      studies are needed to assess the optimal route of administration and the
      frequency of FMT, the best matched donor for each patient as well as the risks
      associated with FMT in IBD.

PMID- 30214267
TI  - Qualitative user evaluation of a revised pharmacogenetic educational toolkit.
AB  - Introduction: Pharmacogenetic (PGx) testing is a leading application for
      personalized and precision medicine; however, there are barriers, including
      limited provider and patient understanding, which affect its uptake. There is a
      need for tools that can enhance the patient and provider experience with testing
      and promoting the shared and informed decision-making. Materials and methods: In
      this study, we sought to gather additional feedback on a PGx toolkit comprised of
      four educational tools that had been previously evaluated through an online
      survey by pharmacists. Specifically, we conducted semi-structured interviews with
      pharmacists and members of the public regarding their understanding and utility
      of the toolkit and its individual components. Results: Participants found three
      of the four toolkit components, a test information sheet, flipbook, and results
      sheet, to be useful and important. The fourth component, results card, was viewed
      less favorably. Participants differed in their preference for medical jargon and
      detailed results nomenclature (namely star * alleles). Conclusion: User input
      during the development of educational materials is essential for optimizing
      utilization, effectiveness, and comprehension.

PMID- 30214268
TI  - Received care compared to ADP-guided care of patients admitted to hospital with
      chest pain of possible cardiac origin.
AB  - Purpose: To assess the extent to which accelerated diagnostic protocols (ADPs),
      compared to traditional care, identify patients presenting to emergency
      departments (EDs) with chest pain who are at low cardiac risk and eligible for
      early ED discharge. Patients and methods: Retrospective study of 290 patients
      admitted to hospital for further evaluation of chest pain following negative ED
      workup (no acute ischemic electrocardiogram [ECG] changes or elevation of initial
      serum troponin assay). Demographic data, serial ECG and troponin results,
      Thrombolysis in Myocardial Infarction (TIMI) score, cardiac investigations, and
      outcomes (confirmed acute coronary syndrome [ACS] at discharge and major adverse
      cardiac events [MACEs]) over 6 months of follow-up were analyzed. A validated ADP
      (ADAPT-ADP) was retrospectively applied to the cohort, and processes and outcomes
      of ADP-guided care were compared with those of care actually received. Results:
      Patients had mean (+/-SD) TIMI score of 1.8 (+/-1.7); six (2.0%) patients were
      diagnosed with ACS at discharge. At 6 months, one patient (0.3%) re-presented
      with ACS and two (0.6%) died of non-coronary causes. The ADAPT-ADP defined 97
      (33.4%) patients as being at low risk and eligible for early ED discharge, but
      who instead incurred mean hospital stay of 1.5 days, with 40.2% in telemetry
      beds, and 21.6% subject to non-invasive testing with only one positive result for
      coronary artery disease. None had a discharge diagnosis of ACS or developed MACE
      at 6 months. Conclusion: Compared to traditional care, application of the ADAPT
      ADP would have allowed one-third of chest pain patients with initially negative
      investigations in ED to have been safely discharged from ED.

PMID- 30214269
TI  - In-hospital outcomes with anterior versus posterior approaches in total hip
      arthroplasty: meta-analysis of randomized controlled trials.
AB  - Purpose: The purpose of this study was to determine whether in-hospital outcomes
      are different with anterior approach (AA) or posterior approach (PA) in primary
      total hip arthroplasty (THA). Methods: We performed a systematic review with
      random-effects meta-analysis of random-ized controlled trials (RCTs) comparing AA
      with PA in primary THA. Hospital outcomes were reported as odds ratio (OR),
      weight mean difference, or standardized mean difference (SMD). Results: A total
      of seven RCTs with 609 patients were included. Outcomes favoring AA included 1.4
      cm shorter incision (p=0.045), 0.5 days shorter hospital stay (p=0.01), 0.5
      points less pain on a 0-10 scale (p=0.007), and less opioid use (SMD=-0.39
      corresponding to 12 fewer morphine equivalents per day, p=0.01). The procedure
      time was 16 minutes longer with AA vs. PA (p=0.002). There were no statistical
      differences between AA and PA in operative blood loss (mean difference =19 mL,
      p=0.71), transfusions (9.7% vs. 16.2%, OR=0.45, p=0.39), or complications (5.5%
      vs. 4.1%, OR=1.42, p=0.62). Conclusion: While the AA to primary THA may take
      longer time compared with the PA, the incision is shorter, and patients report
      slightly less pain, require less opioid medication, and leave the hospital
      earlier. The clinical relevance of these differences during longer-term follow-up
      is uncertain. The choice of surgical approach in primary THA should also consider
      factors such as experience of the surgeon and preferences of the surgeon and
      patient.

PMID- 30214270
TI  - Prevalence of pain-related diagnoses in patients with dementia: a nationwide
      study.
AB  - Purposes: To investigate the prevalence of pain-related diagnoses in patients
      with dementia and evaluate the association of pain-related diagnoses with
      demographic characteristics and dementia subtypes. Patients and methods: In this
      population-based retrospective cohort study, participants were recruited from a
      cohort of 2 million people randomly sampled from the general population in the
      National Health Insurance Research Database of Taiwan from 2000 to 2013. The
      index year was defined as the period of 1 year from the date of the first
      diagnosis of dementia. Results: The study group comprised 28,450 patients with
      the dementia subtypes of vascular dementia, Alzheimer's disease, or other
      dementia subtypes. The mean age of patients with dementia was 76.75 years. Of all
      patients with dementia, 49.07% had at least one pain-related diagnosis documented
      in their outpatient or inpatient claim records within the index year. The top
      three pain-related diagnoses were osteoarthritis (29.27%), headache (12.53%), and
      osteoporosis (11.43%). Musculoskeletal diagnosis was more likely in female
      patients with vascular dementia. Although patients with vascular dementia had a
      significantly lower prevalence of pain-related diagnosis, they had a
      significantly higher risk of 1-year mortality than patients with other dementia
      subtypes. Conclusion: During the index year, 49.07% of patients with dementia had
      at least one pain-related diagnosis. To investigate the differences of the use of
      pain medication in patients with different dementia subtypes and the difference
      of pain-related diagnosis and treatment in patients with and without dementia,
      future studies are recommended.

PMID- 30214271
TI  - Spotlight on cervical vagus nerve stimulation for the treatment of primary
      headache disorders: a review.
AB  - Objectives: Cervical noninvasive vagus nerve stimulation (nVNS) emerged as an
      adjunctive neuromodulation approach for primary headache disorders with limited
      responsiveness to pharmacologic and behavioral treatment. This narrative review
      evaluates the safety and efficacy of invasive and noninvasive peripheral nerve
      stimulation of the cervical branch of the vagal nerve (afferent properties) for
      primary headache disorders (episodic/chronic migraine [EM/CM] and cluster
      headache [ECH/CCH]) and provides a brief summary of the preclinical data on the
      possible mechanism of action of cervical vagus nerve stimulation (VNS) and
      trigemino-nociceptive head pain transmission. Materials and methods: A systematic
      search of published data was performed in PubMed for randomized controlled trials
      (RCTs) and prospective cohort clinical studies assessing the efficacy/safety and
      cost-effectiveness of cervical VNS in primary headache disorders and related
      preclinical studies. Results: Three RCTs were identified for ECH/CCH (ACT-1, ACT
      2 and PREVA), one RCT for migraine (EVENT) and several prospective cohort studies
      and retrospective analyses for both headache disorders. In ACT-1, a significantly
      higher response rate, a higher pain-free rate and a decrease in mean attack
      duration were found in nVNS-treated ECH/CCH patients compared to sham
      stimulation. ACT-2 confirmed these findings (e.g., significantly higher pain-free
      attacks, pain severity decline and increased responder-rate [defined as >=50%
      reduction]). The PREVA study demonstrated the superiority of adjunctive nVNS to
      standard care alone and observed a significantly higher attack reduction (p=0.02)
      and responder rate (defined as >=50% reduction). For CM, the EVENT study assessed
      a significantly higher frequency of decline in the open-label phase. Mostly
      transient mild/moderate adverse events were recorded, and no severe device
      related adverse events occurred. Conclusion: Cervical nVNS represents a novel,
      safe and efficient adjunctive treatment option for primary headache disorders. In
      particular, preliminary observations suggest enhanced nVNS responsiveness in
      favor of episodic subtypes (EM and ECH). However, preclinical studies are
      urgently warranted to dissect the mechanism of action.

PMID- 30214273
TI  - The effect and safety of ozone autohemotherapy combined with pharmacological
      therapy in postherpetic neuralgia.
AB  - Introduction: We investigated the effect and safety of ozone autohemotherapy
      combined with pharmacological therapy in postherpetic neuralgia (PHN). Methods:
      Ninety-eight patients with PHN were enrolled in this study and randomly divided
      into a pharmacological therapy group and ozone autohemotherapy group (49 patients
      in each group). The PHN patients in the pharmacological therapy group were
      administered pharmacological therapy for 2 weeks, whereas PHN patients in the
      ozone autohemotherapy group were given ozone autohemotherapy (200 mL blood from
      patients, the concentration of medical ozone was set as 30 MUg/mL using an ozone
      medical apparatus, 40 mL medical ozone was incubated in 200 mL autologous blood
      for 3-5 minutes) combined with pharmacological therapy for 2 weeks. The Visual
      Analog Scale (VAS), the 50% VAS reduction in the initial value, McGill Pain
      Questionnaire (MPQ), the Patients' Global Impression of Change (PGIC) scale, and
      the World Health Organization Quality of Life (WHOQOL-BREF) instrument were used
      to evaluate the outcomes of all PHN patients before therapy and at 1 week, 1
      month, and 3 months after therapy. Results: Forty-five patients in the
      pharmacological therapy group and 47 patients in the ozone autohemotherapy group
      completed the study. Compared with before therapy, the two groups showed
      significant improvements in VAS, MPQ, PGIC, and WHOQOL-BREF scores after therapy
      (P<0.05). Moreover, compared with the scores of the pharmacological therapy
      group, the ozone autohemotherapy group's scores were significantly improved in
      the VAS, MPQ, PGIC, and WHOQOL-BREF as well as the 50% VAS reduction of the
      initial value after therapy (P<0.05). Finally, there were no statistically
      significant differences in adverse effects between groups after therapy (P>0.05).
      Conclusion: The results of this study demonstrated that ozone autohemotherapy
      combined with pharmacological therapy was superior to isolated pharmacological
      therapy in patients with PHN and was an effective and safe way to relieve PHN.

PMID- 30214272
TI  - Second edition of SIMPAR's "Feed Your Destiny" workshop: the role of lifestyle in
      improving pain management.
AB  - This review is aimed to summarize the latest data regarding pain and nutrition,
      which have emerged during the second edition of Feed Your Destiny (FYD). Theme
      presentations and interactive discussions were held at a workshop on March 30,
      2017, in Florence, Italy, during the 9th Annual Meeting of Study in
      Multidisciplinary Pain Research, where an international faculty, including
      recognized experts in nutrition and pain, reported the scientific evidence on
      this topic from various perspectives. Presentations were divided into two
      sections. In the initial sessions, we analyzed the outcome variables and methods
      of measurement for health claims pertaining to pain proposed under Regulation EC
      No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on
      nutrition and health claims made on foods. Moreover, we evaluated how the
      Mediterranean diet can have a potential impact on pain, gastrointestinal
      disorders, obesity, cancer, and aging. Second, we discussed the evidence
      regarding vitamin D as a nutraceutical that may contribute to pain control,
      evaluating the interindividual variability of pain nature and nurture, and the
      role of micro-RNAs (miRNAs), polyunsaturated omega 3 fatty acids, and phenolic
      compounds, with a final revision of the clinical role of nutrition in tailoring
      pain therapy. The key take-home message provided by the FYD workshop was that a
      balanced, personalized nutritional regimen might play a role as a synergic
      strategy that can improve management of chronic pain through a precision medicine
      approach.

PMID- 30214274
TI  - Both ipsilateral and contralateral localized vibratory stimulations modulated
      pain-related sensory thresholds on the foot in mice and humans.
AB  - Purpose: This study was aimed to investigate the effect of localized vibration on
      sensory thresholds in mice and humans using a novel quantitative method.
      Participants and methods: The sensory thresholds of 7-week-old male C57BL/6J mice
      were measured with four sine-wave electrostimulation frequencies (5, 50, 250, and
      2,000 Hz) before and after applying 2-minute vibration to the plantar side of the
      foot in mice. In human participants (16 males and 16 females; mean age, 21.0+/
      0.8 years), the sensory threshold was measured at 50 Hz before and after applying
      2-minute and 5-minute vibrations to the dorsal side of the foot. Results:
      Application of a 2-minute vibration at either the ipsilateral or contralateral
      side modulated the sensory thresholds elicited by a 5- or 50-Hz right
      electrostimulation in mice. In human participants, application of a 5-minute
      vibration at either the ipsilateral or contralateral side modulated the sensory
      threshold elicited by 50-Hz right electrostimulation, but had no effect on local
      skin temperature. These results suggest that the right side of pain-related
      Adelta fibers (50 Hz) or C fibers (5 Hz) was modulated by the localized
      ipsilateral or contralateral side of vibratory stimuli, respectively, in mice and
      humans. Conclusion: The ability of contralateral vibration to modify the right
      sensory thresholds suggests possible involvement of the central nervous system in
      vibratory modulation.

PMID- 30214275
TI  - Validation study of a diagnostic scoring system for sacroiliac joint-related
      pain.
AB  - Background: There are no specific radiological findings for the diagnosis of
      sacroiliac joint-related pain. A diagnostic scoring system had been developed in
      2017. The score comprised the sum of scores of six items. The score ranged from 0
      to 9 points, and the cutoff was calculated as 4. Objective: To evaluate the
      validity of the diagnostic scoring system for sacroiliac joint-related pain.
      Patients and methods: The sacroiliac joint-related pain group (n=31) comprised
      patients diagnosed with sacroiliac joint-related pain based on patient history,
      physical findings, and responses to analgesic periarticular injection. In
      addition, it was confirmed that they had no other lumbar or hip joint diseases.
      The non-sacroiliac joint-related pain group (n=123) comprised patients with low
      back pain due to a reason other than sacroiliac joint-related pain. We evaluated
      scores for all subjects. We analyzed the differences in each item between both
      groups and performed receiver-operating characteristic curve analysis to evaluate
      the score validity. Results: There were no significant differences in patient
      characteristics between groups. There were significant differences for the
      following four of six items: one-finger test results (P<0.0001), pain while
      sitting on a chair (P=0.0141), sacroiliac joint shear test results (P<0.0001),
      and tenderness of the posterosuperior iliac spine (P<0.0001). The cut-off value
      was 5 points, the area under the curve was 0.80239, sensitivity was 77.4%, and
      specificity was 76.4%. Conclusion: The score demonstrated moderate validity for
      diagnosing sacroiliac joint-related pain.

PMID- 30214276
TI  - Do laws impact opioids consumption? A breakpoint analysis based on Italian sales
      data.
AB  - Purpose: In Italy, where the adoption of opioid analgesics in pain management has
      been historically poor, an increase in opioids consumption occurred between 2000
      and 2015. The aim of this study is to assess, through specific time series
      analyses for trend changes, the impact of different intervening factors - such as
      the availability of new drugs, the observance of clinical guidelines, changes in
      prescription regulations, and in reimbursement policies - on opioids sales to
      community pharmacies in Italy, focusing on the time period 2000-2010. Materials
      and methods: Five opioids were considered: codeine, tramadol, buprenorphine,
      morphine, and fentanyl. The analysis is based on sales data collected at
      wholesale distributors. For each one of the five drugs, time series of the number
      of Defined Daily Doses per thousand inhabitants per day in the period 2000-2010
      were analyzed, and an estimation of breakpoints was performed using segmented
      linear regression. Results: Drug sales underwent a sharp increase in 2000-2010,
      although on different scales. Segmented regression analysis highlighted different
      potential breakpoints, corresponding to either a significant change in value
      and/or in slope. Sales of the five opioids were affected by at least one relevant
      event, often due to a synergy of regulatory, marketing, and technological
      factors. The effect of reimbursement changes has proved important. Conclusion:
      Between 2000 and 2010, regulatory, technological, and reimbursement changes
      significantly influenced opioid sales to community pharmacies in Italy. The sales
      of relatively new drug products seem to be less influenced by changes in
      reimbursement and regulatory policies than that of more established products,
      suggesting that physicians are more comfortable with "old" drugs, since their
      clinical use is supported by established clinical guidelines and protocols.

PMID- 30214277
TI  - Feasibility of percutaneous interbody fusion as a treatment for adjacent
      vertebral stress fracture of ankylosing spondylitis with intervertebral
      pseudarthrosis formation.
AB  - Objective: The objective of this study was to evaluate the feasibility of
      percutaneous interbody fusion (PIF) using bone cement for adjacent vertebral
      stress fracture of ankylosing spondylitis (AS) with intervertebral pseudarthrosis
      formation. Patients and methods: From January 2010 to February 2018, eleven
      consecutive patients (seven men and four women; median age, 56.09+/-13.64 years;
      age range, 33-80 years) who underwent PIF as a treatment for adjacent stress
      fracture of AS with intervertebral pseudarthrosis formation were retrospectively
      analyzed. The Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) score
      were assessed before and after the procedure; meanwhile, the procedure duration,
      length of hospital stay and complications were assessed. Moreover,
      anterior/lateral and computed tomography (CT) scans were utilized for the
      assessment of bone cement distribution and interbody fusion. Results: Technical
      success was achieved in all patients, and they experienced good interbody fusion
      with bone cement after PIF. Mean VAS scores declined significantly from 8.82+/
      0.87 before the procedure to 3.36+/-0.67 1 day after the procedure and 2.73+/
      0.65 1 month after the procedure, while the mean ODI scores decreased from
      82.91+/-3.02 before treatment to 31.64 +/-2.66 1 day after treatment and 30.00+/
      3.10 1 month after treatment. The mean procedure duration was 49.73+/-6.12
      minutes (range, 42-65 minutes). The average length of hospital stay was 7.09+/
      1.45 days (range, 5-10 days). Extraosseous cement leakage occurred in one case
      without causing any clinical complications. Conclusion: PIF is a feasible
      therapeutic technique for adjacent vertebral stress fracture of AS with
      intervertebral pseudarthrosis formation, which can significantly relieve pain and
      stabilize the fractured spine.

PMID- 30214278
TI  - Surgical results and clinical risks of postoperative complications in patients
      with painful malignant spinal cord compression after decompressive surgery.
AB  - Introduction: This study aims to analyze clinical outcome in patients with
      painful malignant spinal cord compression due to advanced cancers after the
      decompressive surgery and identify risk factors for postoperative complications
      in these patients. Furthermore, we created a scoring model to predict the risk of
      postoperative complications based on identified significant risk factors.
      Methods: We retrospectively analyzed survival outcomes, pain outcomes, and
      postoperative complications of patients with painful malignant spinal cord
      compression who were surgically treated in our department. Identification of risk
      factors for postoperative complications was also performed, and significant
      factors according to the multiple logistic regression models were included in the
      scoring model. Results: As a result, 105 patients were enrolled. The overall
      median survival time was 9.1 months (95% CI, 7.1-11.4 months). The mean worst
      pain score was 8.0 in a 24-hour period before surgery, while it decreased to 6.0,
      5.0, 3.5, 3.3, and 3.6 (all P<0.01, when compared with baseline date) at 1 week,
      1 month, 3, 6, and 12 months after surgery, respectively. Similar decreases were
      also observed in the average pain and the pain interference. Thirty-one
      complications occurred within 4 weeks after operation in 26 patients (24.8%,
      26/105). Based on multiple logistic regression models, age (P=0.03), Karnofsky
      performance status (P<0.01), and Charlson Comorbidity Index (P=0.04) were
      significantly associated with postoperative complications and were included in
      the scoring model. Three risk groups were created based on the complication rates
      of each scoring points. The corresponding postoperative complication rates of the
      three groups were 7.7% in group A (0-3 points), 26.7% in group B (4-6 points),
      and 60.9% in group C (7-10 points), respectively (OR, 4.32, 95% CI: 2.24-8.31,
      P<0.01). Conclusion: Decompressive surgery for painful malignant spinal cord
      compression was found to be useful for pain control with a tolerable rate of
      complications. We created a scoring model to predict the risk of postoperative
      complications in patients with painful malignant spinal cord compression after
      surgery. This scoring model may guide doctors to choose the appropriate care
      strategies to realize better pain management.

PMID- 30214280
TI  - Comparison of the efficacy and safety of pregabalin for postherpetic neuralgia in
      Chinese and international patients.
AB  - Purpose: Pregabalin is indicated for postherpetic neuralgia (PHN) in multiple
      countries, including China. This analysis compared pregabalin efficacy and safety
      in Chinese and international patients with PHN. Patients and methods: Data from
      Chinese and international randomized, double-blind, placebo-controlled trials
      were compared. Pregabalin was administered at fixed (150, 300, or 600 mg/day) or
      flexible (150-600 mg/day) doses. The main efficacy measure was mean pain score
      change at endpoint on an 11-point numeric rating scale ranging from 0 = no pain
      to 10 = worst possible pain. Secondary efficacy measures included proportions of
      30% and 50% pain responders, pain-related sleep interference (PRSI) scores, and
      proportions of Patient Global Impression of Change (PGIC) responders. The
      incidences of serious adverse events (SAEs) and adverse events (AEs) were used to
      assess safety. The effect of baseline pain severity on efficacy was tested. The
      proportions of patients with severe baseline pain who had moderate or mild pain
      at endpoint were also assessed. Results: A total of 1166 patients were analyzed:
      312 Chinese and 854 international. Overall, results were similar between Chinese
      and international patients. Pregabalin statistically significantly improved mean
      pain score versus placebo (least squares mean difference [95% CIs]: Chinese, -0.8
      [-1.2, -0.5]; international, -1.3 [-1.6, -1.0]; both p<0.001). Pregabalin was
      statistically significantly better than placebo in Chinese and international
      patient groups in the proportions of 30% and 50% pain responders, PRSI scores,
      and proportions of PGIC responders. Baseline pain severity did not affect
      efficacy, except for some measures in Chinese patients with moderate baseline
      pain. Similar proportions of pregabalin-treated patients with severe baseline
      pain had moderate or mild pain at endpoint in both groups. SAE and AE profiles
      were comparable in Chinese and international patient groups, except incidences
      were commonly higher in international patients. Conclusion: Chinese and
      international patients with PHN exhibit comparable pregabalin efficacy and
      safety, highlighting the utility of pregabalin for diverse PHN patient
      populations.

PMID- 30214279
TI  - Current pain management strategies for patients with erythromelalgia: a critical
      review.
AB  - Erythromelalgia (EM) is a rare disorder characterized by erythematous, warm,
      painful extremities, which is often precipitated by cold conditions. The
      pathophysiology of EM is incompletely understood. Recent investigations have
      identified sodium channelopathy as a genetic cause for this pain condition,
      classified as primary inherited EM. Other subtypes are idiopathic EM and
      secondary EM. The management of pain in EM is challenging as no single therapy
      has been found to be effective. There is varying response to pharmacotherapy and
      significant variability within this clinical population, resulting in a stepwise
      trial and error approach. Consequently, EM is often associated with poorer health
      related quality of life with higher morbidity. There is currently no consensus or
      guidelines on management of pain in EM. This is a review of the literature on
      management of pain using pharmacologic, procedural intervention and
      nonpharmacologic treatment in children and adults with EM.

PMID- 30214281
TI  - The impact of fluoroscopic confirmation of thoracic imaging on accuracy of
      thoracic epidural catheter placement on postoperative pain control.
AB  - Background: Thoracic epidural analgesia (TEA) provides superior postoperative
      pain control compared to parenteral opioids after major thoracic and abdominal
      surgeries. However, some studies with respect to benefits of continuous TEA have
      shown mixed results. The purpose of this study was to determine the rate of
      successful TEA catheter insertion into the epidural space using contrast
      fluoroscopy and the impact of placement location on postoperative analgesia and
      opioid use. Patients and methods: After Advocate health care institutional review
      board approval, we conducted a prospective, open-label, single intervention study
      on patients undergoing thoracic or upper abdominal surgery. A thoracic paramedian
      epidural approach and a loss of resistance to saline technique were used to place
      an epidural catheter above the T11 level and fluoroscopic images with injected
      contrast were taken to locate the catheter tip in the epidural space. Results:
      Twenty-five subjects were included in the study, of which 3 catheters (12%) were
      not identified as being in the epidural space. We found an average difference of
      1.5 vertebral levels between clinical and radiological assessments of catheter
      tips. Thirteen catheters (52%) were more than 1 vertebral level away from the
      clinically assessed level. No significant difference was found in the pain scores
      at 1, 24, and 48 hours after surgery between patients with correct versus
      incorrect catheter placement. Less opioids were used in the correct catheter
      placement group at 24 hours (256 morphine milligram equivalent [MME] vs 201 MME)
      and at 48 hours after surgery (250 MME vs 173 MME), but it was not statistically
      significant (p=0.149 and p=0.068, respectively). Conclusion: Improvement in
      assuring success in the technique for TEA catheter placement following major
      thoracic or upper abdominal surgery exists, for which contrast-enhanced
      fluoroscopy might be a promising solution.

PMID- 30214282
TI  - Differences in clinical characteristics and mutational pattern between
      synchronous and metachronous colorectal liver metastases.
AB  - Purpose: To investigate differences in clinical characteristics and mutational
      patterns between synchronous and metachronous colorectal liver metastases (CLMs).
      Patients and methods: From June 2008 to December 2014, patients with RAS wild
      type CLMs treated at Zhongshan Hospital, Fudan University were included. DNA
      extracted from formalin-fixed paraffin-embedded tissue of primary tumors was
      sequenced with next-generation sequencing for single-nucleotide polymorphism of
      96 genes according to custom panel. Mutations were compared between synchronous
      and metachronous liver metastases and correlated with clinical characteristics.
      Results: A total of 161 patients were included: 93 patients with synchronous CLM
      and 68 patients with metachronous CLM. Patients with metachronous CLM were
      obviously elder. For pathology of primary tumors, synchronous CLMs were larger in
      size, poorly differentiated, and more frequently local advanced and lymph node
      positive. For evaluation of liver metastases, synchronous CLM had more and larger
      metastatic lesions. The median number of mutations in synchronous CLMs was
      significantly higher than in metachronous group (22 vs. 18, p<0.001). EGFR
      rs2227983 is the most prevalent mutation in both groups and only a part of
      prevalent mutations is shared in both groups. Prevalent mutations were correlated
      with many clinical characteristics. EGFR rs2227983, RBMXL3 rs12399211, and PTCH1
      rs357564 were prognostic for latency of metachronous CLM. Conclusion: Clinically,
      synchronous CLMs, compared with metachronous CLMs, were younger and showed
      heavier tumor burden for both primaries and liver metastases. Genetically, we
      identified different mutational patterns between synchronous and metachronous
      CLMs and several correlations between mutations and clinical characteristics.
      Further researches were needed to confirm these potential key mutations of CLMs.

PMID- 30214283
TI  - Long-term oncologic outcomes of papillary thyroid microcarcinoma according to the
      presence of clinically apparent lymph node metastasis: a large retrospective
      analysis of 5,348 patients.
AB  - Purpose: Active surveillance (AS) of low-risk papillary thyroid microcarcinoma
      (PTMC) may reduce the risk of overtreatment of clinically insignificant cancer.
      However, the absence of predictor for the progression of PTMC resulted in
      treatment delay and potentially compromising cure of aggressive disease.
      Therefore, to anticipate potential damage of delayed surgery, we investigated the
      oncologic outcomes of patients with low-risk PTMC initially eligible for AS
      except clinically apparent lymph node metastasis (LNM), imitating delayed surgery
      with neck dissection. Materials and methods: A total of 5,348 patients, enrolled
      between 1987 and 2016, with low-risk PTMC initially eligible for AS were included
      regardless of LNM. We classified our study patients into two groups: Group I,
      lobectomy with prophylactic central cervical node dissection; Group II, total
      thyroidectomy with modified radical neck dissection for LNM. In addition, we
      investigated the oncological outcomes of patients with second-wave surgery due to
      lateral lymph node recurrence (Group III, subgroup of Group I). Results: Group I
      showed more favorable clinicopathological characteristics compared with Group II.
      In Group I, only 29 (0.58%) of 4,927 patients underwent second-wave surgery with
      neck dissection for lateral lymph node recurrences, whereas in Group II, all 22
      (5.23%) of 421 patients underwent second-wave selective node dissection because
      of nodal recurrence. Disease-free survival rates were significantly different
      between Groups I and II (P<0.05). Of note, the recurrence rate of Group II was
      still significantly higher than that of Group III (5.2% vs 0%, respectively;
      P=0.021). In addition, Kaplan-Mayer survival analysis indicated poor disease-free
      survival rates in Group II compared with Group III (P<0.05). Conclusion: The long
      term treatment outcome of PTMC without LNM was favorable even if the recurrence
      occurs during follow-up period compared with that of PTMC with LNM. It should be
      noted that AS might be able to cause poor prognosis due to clinically apparent
      LNM.

PMID- 30214284
TI  - The role of CCN4/WISP-1 in the cancerous phenotype.
AB  - CCN proteins are secreted into the extracellular environment where they interact
      with both components of the extracellular matrix and with cell surface receptors
      to regulate cellular function. Through these interactions, CCNs act as
      extracellular ligands to activate intracellular signal transduction pathways.
      CCN4/WISP-1, like other CCNs, plays multiple physiologic roles in development and
      also participates in pathogenesis. CCN4 is of particular interest with respect to
      cancer, showing promise as a biomarker or prognostic factor as well as a
      potential therapeutic target. This review focuses on recent work addressing the
      role of CCN4 in cancer. While CCN4 has been identified as an oncogene in a number
      of cancers, where it enhances cell migration and promoting epithelial-mesenchymal
      transition, there are other cancers where CCN4 appears to play an inhibitory
      role. The mechanisms underlying these differences in cellular response have not
      yet been delineated, but are an active area of investigation. The expression and
      activities of CCN4 splice variants are likewise an emerging area for study. CCN4
      acts as an autocrine factor that regulates the cancer cells from which it is
      secreted. However, CCN4 is also a paracrine factor that is secreted by stromal
      fibroblasts, and can affect the function of vascular endothelial cells. In
      summary, current evidence is abundant in regard to establishing potential roles
      for CCN4 in oncogenesis, but much remains to be learned about the functions of
      this fascinating protein as both an autocrine and paracrine regulator in the
      tumor microenvironment.

PMID- 30214285
TI  - Trichostatin A promotes GLI1 degradation and P21 expression in multiple myeloma
      cells.
AB  - Background: Histone deacetylase inhibitors are promising drugs for the future
      application in cancer therapy. Trichostatin A (TSA), a histone deacetylase
      inhibitor, exhibits effective antitumor effects in various cancers. However, the
      effects and underlying mechanisms of TSA on multiple myeloma (MM) are not fully
      investigated. Methods: In the present study, RPMI8226 and MM.1S cells treated
      with TSA were used for cell proliferation, cell cycle, and survival examinations,
      then the localization and post transcriptional modification of GLI1 protein as
      well as the target gene P21 were analyzed using immunofluorescence,
      immunoprecipitation, western blots and qPCR, respectively. Results: TSA exerted a
      time and dose-dependent cytotoxicity on MM cell lines, and suppressed the
      proliferation of MM cells and induced an upregulation of p21 protein accompanied
      by a decreased expression of cyclin D1. TSA treatment led to a downregulation of
      GLI1, and the nuclear accumulation of GLI1 was also inhibited. As a result of
      hedgehog inhibition, the expression of MYC and SURVIVIN was greatly weakened
      after TSA treatment. Furthermore, TSA accelerated GLI1 degradation in a
      proteasome-dependent manner. Additionally, p21 induction also contributed to GLI1
      downregulation via reducing the transcription of GLI in mRNA level. Rescue
      experiments verified that exogenous expression of GLI1 alleviated MM cell
      apoptosis induced by TSA. Conclusion: These results indicated that TSA represses
      MM cell growth and induces cell apoptosis. The inhibition of hedgehog signaling
      is an important mechanism accounting for the cytotoxic effects of TSA.

PMID- 30214286
TI  - Efficacy and safety of TAS-102 in refractory metastatic colorectal cancer: a meta
      analysis.
AB  - Background: TAS-102 has been applied to metastatic colorectal cancer (mCRC)
      patients who had received at least two prior regimens of standard chemotherapy.
      This meta-analysis is designed to assess the efficacy and safety of TAS-102 in
      patients with mCRC. Methods: We searched randomized controlled trials (RCTs)
      through PubMed, Embase, Web of Science and Cochrane clinical trial databases and
      clinicaltrial.gov from database initiation to March 2018. The overall survival
      (OS), progression-free survival (PFS), disease control rate (DCR) and incidence
      of adverse events were summarized with the use of hazard ratio (HR) or risk ratio
      (RR). Results: Three RCTs with 1318 patients were included. Results showed that
      TAS-102 significantly improved OS (HR 0.70, 95% confidence interval [CI] 0.62
      0.79) and PFS (HR 0.46, 95% CI 0.40-0.52) in patients who were intolerant or
      refractory to fluoropyrimidine, irinotecan and oxaliplatin. The pooled odds ratio
      of DCR was 4.15 (95% CI 3.18-5.43). Notably, there were significant OS benefits
      both in patients with KRAS mutation (HR 0.76, 95% CI 0.63-0.92) and those with
      wild-type KRAS (HR 0.66, 95% CI 0.55-0.79). These benefits were also observed in
      patients with different numbers of metastatic sites. However, patients with >18
      months since the diagnosis of first metastases seemed to have better OS (HR 0.65,
      95% CI 0.55-0.77). The most common toxicities associated with TAS-102 were
      neutropenia (RR 116.51, 95% CI 23.51-577.33), leucopenia (RR 67.70, 95% CI 13.63
      336.29), anemia (RR 4.28, 95% CI 2.70-6.79) and diarrhea (RR 5.10, 95% CI 1.40
      18.61). Conclusion: TAS-102 significantly improves OS, PFS and DCR in refractory
      mCRC patients with tolerable toxicity. Meanwhile, the OS benefits have nothing to
      do with KRAS status and the number of metastatic sites.

PMID- 30214287
TI  - TNM-PNI: a novel prognostic scoring system for patients with gastric cancer and
      curative D2 resection.
AB  - Purpose: Gastric cancer (GC) is one of the most common malignancies and has a
      high mortality rate. In recent years, several nutritional or inflammatory
      biomarkers have been shown to effectively predict the prognosis of tumors. In
      this study, we intended to establish a prognostic scoring system for GC patients.
      Patients and methods: Our study included a total of 501 GC patients who were
      diagnosed with GC stage I-III and received curative gastrectomy with D2
      lymphadenectomy between January 2011 and December 2012. Survival analysis was
      performed using Kaplan-Meier and log-rank tests. Two Cox multivariate models, one
      for continuous and one for categorical variables, were established to identify
      independent prognostic factors. All statistical analyses were performed using
      SPSS 20.0. Results: Univariate and multivariate analyses revealed that tumor-node
      metastasis (TNM) stage, preoperative prognostic nutritional index (PNI), and
      adjuvant therapy were independent prognostic factors for GC patients. We
      established a new composite variable, TNM-PNI, which was confirmed to be a major
      prognostic factor for curative D2 resection, independent of whether adjuvant
      therapy was administered. GC patients with higher TNM-PNI scores always had worse
      cancer outcomes. In addition, we found that adjuvant therapy might be beneficial
      for the survival of GC patients with TNM-PNI =4 or 5. Conclusion: Preoperative
      PNI plays a distinctly subsidiary role to the TNM stage when predicting patient
      prognosis. TNM-PNI is a novel and an effective prognostic index for GC patients
      with curative D2 resection and a good supplement for the National Comprehensive
      Cancer Network Guidelines.

PMID- 30214288
TI  - Incidence of bone metastasis and factors contributing to its development and
      prognosis in newly diagnosed renal cell carcinoma: a population-based study.
AB  - Purpose: The purpose of this study was to assess the incidence of and the risk
      factors and prognostic factors for bone metastasis (BM) in initial metastatic
      renal cell carcinoma (RCC) based on a large population analysis. Patients and
      methods: Data were obtained for a total of 45,824 RCC patients recorded in the
      database of the Surveillance, Epidemiology, and End Results program of the
      National Cancer Institute between 2010 and 2014. Multivariate logistic and Cox
      regression analyses were used to identify the risk factors and prognostic factors
      associated with BM in RCC patients. Kaplan-Meier analysis was used to estimate
      the overall survival of RCC patients, and the difference between the survival
      curves was tested by log-rank tests. Results: A total of 1,509 (3.29%) patients
      were diagnosed with bone metastases at initial diagnosis. Male gender, higher T
      stage, lymph node involvement, poor tumor grade, presence of lung, liver, and
      brain metastases, and the collecting duct type of RCC were positively associated
      with BM occurrence. The median survival time for RCC patients with bone
      metastases was 12.0 (95% confidence interval [CI]: 10.69-13.31) months, and the
      survival time for those with collecting duct, clear-cell, papillary, and
      chromophobe subtypes of RCC were 3 (95% CI: 0.23-5.77), 13 (95% CI: 11.60-14.40),
      8 (95% CI: 5.09-10.91), and 11 (95% CI: 5.02-16.98) months; these differences
      were significantly different (P<0.01). Older age, higher T stage, lymph node
      involvement, poor tumor grade, the presence of lung, liver, and brain metastases,
      collecting duct RCC, and the absence of surgical treatments were the factors
      associated with worse prognoses. Conclusion: BM was highly prevalent and
      significantly decreased the survival rate of RCC patients. A number of factors
      associated with the development and prognosis of BM were identified, and these
      insights provide preventive guidelines for screening and treatment of BM in RCC
      patients.

PMID- 30214289
TI  - Computational analysis of mRNA expression profiles identifies a novel triple
      biomarker model as prognostic predictor of stage II and III colorectal
      adenocarcinoma patients.
AB  - Introduction: Although remarkable progress has been made to determine the
      prognosis of patients with colorectal cancer (CRC), it is inadequate to identify
      the subset of high-risk TNM stage II and stage III patients that have a high
      potential of developing tumor recurrence and may experience death. In this study,
      we aimed to develop biomarkers as a prognostic signature for the clinical outcome
      of CRC patients with stage II and stage III. Materials and methods: We performed
      a systematic and comprehensive discovery step to identify recurrence-associated
      genes in CRC patients through publicly available GSE41258 (n=253) and GSE17536
      (n=107) datasets. We subsequently determined the prognostic relevance of
      candidate genes in stage II and III patients and developed a triple-biomarker for
      predicting RFS in GSE17536, which was later validated in an independent cohort
      GSE33113 dataset (n=90). Results: Based upon mRNA expression profiling studies,
      we identified 45 genes which differentially expressed in recurrent vs non
      recurrent CRC patients. By using Cox proportional hazard models, we then
      developed a triple-marker model (THBS2, SERPINE1, and FN1) to predict prognosis
      in GSE17536, which successfully identified poor prognosis in stage II and stage
      III, particularly high-risk stage II CRC patients. Discussion: Notably, we found
      that our triple-marker model once again predicted recurrence in stage II patients
      in GSE33113. Kaplan-Meier survival analysis demonstrated that patients with high
      scores have a poor outcome compared to those with low scores. Our triple-marker
      model is a reliable predictive tool for determining prognosis in CRC patients
      with stage II and stage III, and might be able to identify high-risk patients
      that are candidates for more targeted personalized clinical management and
      surveillance.

PMID- 30214290
TI  - Diagnostic potential of methylated DAPK in brushing samples of nasopharyngeal
      carcinoma.
AB  - Background: The death-associated protein kinase (DAPK) gene is an important
      member of the apoptotic pathway and is inactivated by abnormal methylation in
      numerous cancers, including nasopharyngeal carcinoma (NPC). However, the
      diagnostic value of DAPK methylation in brushing samples and tissue samples of
      NPC remains unclear. Methods: We conducted a systematic meta-analysis based on 17
      studies (including 386 tissue cases, 233 brushing cases, and 296 blood cases).
      Results: Our results revealed an association between methylated DAPK and
      increased risk of NPC in blood, brushing, and tissue samples. In addition, the
      comparison of the pooled sensitivity, specificity, and area under the curve of
      methylated DAPK in brushing and tissue samples demonstrated the non-inferior
      effectiveness of methylated DAPK in brushing samples to monitor the development
      of NPC.

PMID- 30214291
TI  - Relationship between IGF2BP2 and IGFBP3 polymorphisms and susceptibility to non
      small-cell lung cancer: a case-control study in Eastern Chinese Han population.
AB  - Background: IGF2BP2 and IGFBP3 polymorphisms may be associated with cancer risk.
      Methods: With an aim to determine the association of variations in IGF2BP2 and
      IGFBP3 genes with risk of non-small-cell lung cancer (NSCLC), IGF2BP2 rs1470579
      A>C, rs4402960 G>T and IGFBP3 rs2270628 C>T, rs3110697 G>A, and rs6953668 G>A
      polymorphisms were selected and genotyped in 521 NSCLC patients and 1,030
      controls. Results: We found that there was no difference in IGF2BP2 and IGFBP3
      genotype distribution among the NSCLC patients and controls. The stratified
      analyses suggested that IGF2BP2 rs1470579 A>C polymorphism decreased the risk of
      NSCLC in some subgroups (female subgroup: CC vs AA: adjusted P=0.032 and CC vs
      AC/AA: adjusted P=0.028; <60 years subgroup: CC vs AA: adjusted P=0.012 and CC vs
      AC/AA: adjusted P=0.013; and never drinking subgroup: CC vs AA: adjusted P=0.046
      and CC vs AC/AA: adjusted P=0.031). The stratified analyses also found that
      IGF2BP2 rs4402960 G>T polymorphism decreased the risk of NSCLC in some subgroups
      (female subgroup: TT vs GG: adjusted P=0.031 and TT vs GT/GG: adjusted P=0.026;
      <60 subgroup: TT vs GG: adjusted P=0.037 and TT vs GT/GG: adjusted P=0.038; and
      never drinking subgroup: TT vs GT/GG: adjusted P=0.046). Haplotype analysis
      indicated Ars1470579Crs2270628Grs3110697Grs4402960Ars6953668 haplotype decreased
      susceptibility of NSCLC (P=0.007). Conclusion: Our study suggests that IGF2BP2
      rs1470579 A>C, rs4402960 G>T single-nucleotide polymorphisms are candidates for
      decreased susceptibility to NSCLC among female, <60 years, and never drinking
      subgroups. In the future, more case-control studies with functional analysis are
      needed to confirm these preliminary findings.

PMID- 30214292
TI  - Treatment outcomes of ureteral stenting for malignant extrinsic ureteral
      obstruction: a comparison between polymeric and metallic stents.
AB  - Purpose: To compare treatment outcomes, more specifically patency rate, of
      polymeric and metallic stents for malignant ureteral obstruction. Patients and
      methods: Between August 2007 and September 2017, we retrospectively analyzed the
      data of 92 patients (126 ureters) having a diagnosis of malignant extrinsic
      ureteral obstruction treated with indwelling ureteral stents (polymeric and full
      length metallic stents). Of these patients, 35 (54 ureters) were treated with
      polymeric stents and 57 (72 ureters) with a Resonance(r) metallic stent. The
      observation period was censored to 1 year. Survival rate in cases of malignant
      ureteral obstruction was calculated, and the relationship between the causes of
      ureteral obstruction, the stent type, and the patency rate was evaluated.
      Results: The median observation period was 145 days, with a median survival time
      of 258 days. The stent patency rate was 70.9% at 1 year, regardless of stent
      type. Stent occlusion was observed in 20 patients (33 ureters). According to
      stent type, occlusion of the polymeric and metallic stents was identified in 12
      (22%) and 8 (11%) cases, respectively. The clinical features associated with
      stent failure were assessed. In univariate analysis, the patency rate was
      significantly better for the metallic stent than for the polymeric stent (1-year
      patency rate; 78.4%, 61.1%, respectively, HR, 2.15; 95% CI, 1.07-4.33; p=0.031).
      However, the patency rate among patients with abdominal dissemination, lymph node
      metastasis, and direct compression by tumor was not significantly different.
      Conclusion: Indwelling ureteral stents, particularly metallic stents, are
      effective for the treatment of malignant ureteral obstruction.

PMID- 30214293
TI  - Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor
      prognosis in penile squamous cell carcinoma.
AB  - Purpose: Molecular biomarkers, especially serologic factors, have been widely
      applied in cancer diagnosis and patient follow-up. However, there are few
      valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the
      authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum
      LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the
      prediction of survival in PSCC. Patients and methods: This study included 114
      PSCC patients. Reverse transcription-quantitative polymerase chain reaction,
      Western blotting, and immunohistochemistry were performed to detect LAMC2
      expression; enzyme-linked immunosorbent assays were used to test sLAMC2
      concentration; and a Transwell assay and an in vivo experiment in nude mice were
      used to test PSCC cell migration, invasion, and metastasis. The chi-squared test
      was used to analyze the association between LAMC2 level and clinical parameters,
      the Cox proportional hazards regression model was used to evaluate the hazard
      ratio for death, and Kaplan-Meier analysis with a log-rank test was used for the
      survival analysis. Results: LAMC2 was overexpressed in PSCC tissues, and the
      LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in
      primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and
      sLAMC2 were higher in patients with LN metastasis than in those without LN
      metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial
      to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of
      PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with
      advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients
      and predicted shorter disease-specific survival. The predictive value of sLAMC2
      is superior to that of C-reactive protein and squamous cell carcinoma antigen
      previously reported in PSCC patients, and a stratification analysis revealed that
      the level of sLAMC2 had a higher predictive value for disease-specific survival
      in early penile cancer (especially at the N0/X stage) than in later-stage penile
      cancer. Conclusion: These findings suggest that sLAMC2 is a potential serologic
      prognostic marker in PSCC and could aid in risk stratification in early-stage
      PSCC patients.

PMID- 30214294
TI  - Distinct prognostic values of mRNA expression of glutathione peroxidases in non
      small cell lung cancer.
AB  - Introduction: Glutathione peroxidases (GPxs) constitutes an enzyme family which
      has the ability to reduce free hydrogen peroxide to water and lipid
      hydroperoxides to their corresponding alcohols, and its main biological roles are
      to protect organisms from oxidative stress-induced damage. GPxs include eight
      members in different tissues of the body, and they play essential roles in
      carcinogenesis. However, the prognostic value of individual GPx in non-small cell
      lung cancer (NSCLC) remains elusive. Materials and methods: In the current study,
      we investigated the prognostic value of GPxs in NSCLC patients through the
      "Kaplan-Meier plotter" database, wherein updated gene expression data and
      survival information from a total of 1,926 NSCLC patients are included. Results:
      High expression of GPx1 mRNA was correlated with worse overall survival (OS) in
      adenocarcinoma patients. High expression of GPx2 mRNA was correlated with worse
      OS for all NSCLC patients. In contrast, high expression of GPx3 mRNA was
      associated with better OS for all NSCLC patients. High expression of GPx4 mRNA
      was significantly correlated with worsening adenocarcinoma in these patients.
      GPx5 mRNA high expression correlated with worsening OS for all NSCLC patients.
      Discussion: The current findings of prognostic values of individual mRNA
      expression of GPxs in NSCLC patients indicate some GPxs may have prognostic value
      in NSCLC patients, and this needs further study.

PMID- 30214295
TI  - A cumulative score based on preoperative fibrinogen and the neutrophil-lymphocyte
      ratio to predict outcomes in resectable gastric cancer.
AB  - Background: Recent studies have revealed that preoperative fibrinogen and the
      neutrophil-lymphocyte ratio (NLR) are associated with poor outcome in gastric
      cancer (GC). We aimed to evaluate whether the fibrinogen and the NLR score had a
      consistent prognostic value for resectable GC. Methods: We analyzed 1,293
      consecutive patients who underwent curative surgery for GC. The F-NLR score was 2
      for patients with hyperfibrinogenemia (>400 mg/dL) and elevated NLR (>=5.0), 1
      for those with one abnormal index, and 0 for those with no abnormal indices.
      Results: We found that higher F-NLR scores were associated with larger tumor
      size, deeper tumor invasion and more lymph node metastasis (all P<0.05). In a
      multivariate analysis, F-NLR independently predicted postoperative survival
      (P<0.001). When stratified by tumor-node-metastasis (TNM) stage, the prognostic
      value of F-NLR was still maintained for stages I-II (P<0.001) and stage III
      (P=0.003). Of note, F-NLR also effectively stratified overall survival (OS)
      irrespective of age, adjuvant chemotherapy administration, tumor location and
      histological grade (all P<0.05). Furthermore, F-NLR and TNM stratified 5-year OS
      from 61% (F-NLR 0) to 15% (F-NLR 2) and from 92% (stage I) to 37% (stage III),
      respectively. Utilizing both F-NLR and TNM, 5-year OS ranged from 93% (F-NLR 0,
      TNM I) to 6% (F-NLR 2, TNM III). Conclusion: The F-NLR score independently
      predicts outcomes in GC patients after curative surgery. Therefore, it should be
      implemented in routine clinical practice for identifying more high-risk patients.

PMID- 30214296
TI  - The predictive value of cumulative toxicity for quality of life in patients with
      metastatic colorectal cancer during first-line palliative chemotherapy.
AB  - Background: Studies evaluating new systemic agents tend to report severe
      toxicities only, while the cumulative effect of multiple lower grade adverse
      events (AEs) may have an additional negative impact on patient quality of life
      (QOL). In the current observational cohort study, we evaluated whether, in
      patients with metastatic colorectal cancer receiving first-line chemotherapy,
      cumulative toxicity comprising all grades of AEs is more predictive for QOL than
      cumulative toxicity due to only high-grade AEs. Methods: One hundred and five
      patients starting treatment completed the European Organization for the Research
      and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
      questionnaire at baseline and 10 weeks. AEs, clinical outcomes, and demographics
      were retrieved from patient records. Cumulative toxicity scores were calculated
      in three ways: total number of high-grade AEs, total number of all-grade AEs, and
      total number of AEs multiplied by their grade (the severity score). Relations
      between cumulative toxicity scores and QOL were studied using multivariable
      linear regression analyses. Results: The mean age of patients was 65 years, 68%
      were male, and 84% received oxaliplatin-based chemotherapy. A higher total number
      of AEs of all grades (B=-2.4, 95% CI=-3.9; -0.9) and the severity score (B=-1.4,
      95% CI=-2.3; -0.5) were predictive for clinically relevant changes in physical
      QOL, whereas the total high-grade AEs was not. None of the cumulative toxicity
      scores were predictive for global QOL. Conclusion: Cumulative toxicity scores
      comprising all grades of AEs provide a better measure of treatment burden than a
      toxicity score comprising high-grade AEs only. Physical QOL seems to be more
      affected by AEs than global QOL. Our results emphasize that future clinical
      trials should present cumulative toxicity scores comprising all AE grades as well
      as physical QOL instead of global QOL.

PMID- 30214297
TI  - Prognostic value of aspartate aminotransferase to platelet ratio index as a
      noninvasive biomarker in patients with hepatocellular carcinoma: a meta-analysis.
AB  - Background: The aspartate aminotransferase-to-platelet ratio index (APRI) has
      been correlated with clinical outcome in patients with hepatocellular carcinoma
      (HCC), but controversial results were obtained with previous studies. This study
      was aimed to evaluate the prognostic value of the APRI in patients with HCC.
      Materials and methods: A literature survey was conducted by searching PubMed, Web
      of Science, Cochrane library, Embase, Wanfang, and National Knowledge
      Infrastructure for publications released prior to March 1, 2018. Pooled hazard
      ratios (HRs) with 95% CIs were calculated to assess the association between the
      APRI and HCC prognosis using Stata SE 12.0 software. Results: Analysis was
      performed on a total of 15 articles that included 5,051 patients. The pooled
      results showed that APRI was significantly associated with overall survival for
      patients with HCC (HR =1.62, 95% CI: 1.23-2.01). Furthermore, HCC patients with
      higher APRI were at significantly greater risk of short recurrence-free survival
      (HR =1.83, 95% CI: 1.48-2.18) and poor disease-free survival (HR =1.46, 95% CI:
      1.26-1.66). Conclusions: APRI could serve as a promising and noninvasive marker
      for predicting HCC prognosis.

PMID- 30214298
TI  - Quantitative assessment of aberrant P16INK4a methylation in ovarian cancer: a
      meta-analysis based on literature and TCGA datasets.
AB  - Epigenetic alteration of P16INK4a is conventionally thought to induce the
      initiation of carcinoma. However, the role of P16INK4a methylation in ovarian
      cancer still remains controversial. Therefore, we performed a meta-analysis to
      further elucidate the relationship between P16INK4a promoter methylation and
      ovarian cancer. A total of 24 studies, including 20 on risk, 10 on
      clinicopathological features, and 3 on prognosis, were included in our meta
      analysis. Our results indicated that the frequency of P16INK4a methylation in
      cancer tissues was significantly higher than normal tissues and low malignant
      potential tumor tissues (odds ratio [OR] =5.01, 95% CI=1.55-16.14; OR =1.88, 95%
      CI=1.10-3.19, respectively), but similar to benign tissues (OR =1.18, 95% CI=0.52
      2.65). Furthermore, P16INK4a promoter methylation was not strongly correlated
      with age, clinical stage, tumor differentiation, or histological subtype in
      patients with ovarian cancer. Additionally, survival analysis showed that
      patients with P16INK4a promoter methylation had a shorter progression-free
      survival in univariate and multivariate Cox regression models (hazard ratio
      =1.68, 95% CI=1.26-2.24; hazard ratio =1.55, 95% CI=1.15-2.08; respectively). In
      The Cancer Genome Atlas datasets, the methylation levels of seven out of nine CpG
      sites were significantly increased in the ovarian tumor tissues compared with the
      normal tissues. In conclusion, the present meta-analysis suggests that P16INK4a
      promoter methylation may be useful in distinguishing malignant cancer from
      healthy ovarian tissues, and it may be a potential predictive marker for
      prognosis in patients with ovarian cancer.

PMID- 30214299
TI  - Analysis of potential genes associated with primary cilia in bladder cancer.
AB  - Background: Dysfunction of primary cilia (PC), which could influence cell cycle
      and modulate cilia-related signaling transduction, has been reported in several
      cancers. However, there is no evidence of their function in bladder cancer
      (BLCA). This study was performed to investigate the presence of PC in BLCA and to
      explore the potential molecular mechanisms underlying the PC in BLCA. Patients
      and methods: The presence of PC was assessed in BLCA and adjacent non-cancerous
      tissues. The gene expression dataset GSE52519 was employed to obtain
      differentially expressed genes (DEGs) associated with PC. The mRNA expression of
      the DEGs were confirmed by Gene Expression Profiling Interactive Analysis. The
      DEGs properties and pathways were analyzed by Gene ontology and Kyoto
      Encyclopedia of Genes and Genomes pathway enrichment analysis. Genomatix software
      was used to predict putative transcription factor binding sites (TFBS) in the
      promoter region of DEGs, and the transcription factors were achieved according to
      the shared TFBS, which were supported by the ChIP-Sequence data. Results: PC were
      found to be reduced in BLCA tissue samples in this study. Seven DEGs were
      observed to be associated with PC, and gene ontology and Kyoto Encyclopedia of
      Genes and Genomes pathway enrichment analysis indicated that these DEGs exhibited
      the properties and functions of PC, and that the Hedgehog signaling pathway
      probably participated in the pathogenesis and progression of BLCA. The mRNA
      expression of the seven DEGs in 404 BLCA and 28 normal tissue samples were
      analyzed, and five DEGs including CENPF, STIL, AURKA, STK39 and OSR1 were
      identified. Five TFBS including CREB, E2FF, EBOX, ETSF and HOXF in the promoter
      region of five DEGs were calculated and the transcription factors were obtained
      according to the shared TFBS. Conclusion: PC were found to be reduced in BLCA,
      and the potential molecular mechanisms of PC in BLCA helped to provide novel
      diagnosis and therapeutic targets for BLCA.

PMID- 30214300
TI  - Silencing the expression of copine-III enhances the sensitivity of hepatocellular
      carcinoma cells to the molecular targeted agent sorafenib.
AB  - Background: The application of the oral targeted therapeutic agent sorafenib
      provides new hope for patients suffering from advanced stages of hepatocellular
      carcinoma (HCC), but the prognosis of such patients remains poor due to the rapid
      development of the multidrug resistance process in cancer pathogenesis. The
      present work evaluated whether copine-III, a novel cancer regulator encoded by
      the CPNE3 gene, would be a potential indicator of sorafenib resistance in HCC
      treatment. Materials and methods: The endogenous expression of copine-III in
      clinical specimens was examined by quantitative polymerase chain reaction. Copine
      III siRNA was transfected into HCC cells to downregulate copine-III expression.
      The effect of copine-III on sorafenib's antitumor activation was identified by in
      vitro and in vivo experiments (MTT, Transwell, and flow cytometry as well as a
      nude mice model). Results: High levels of copine-III in clinical specimens are
      related to poor prognosis of advanced HCC patients on sorafenib treatment.
      Infection of Ad-siCPNE3 significantly decreased the endogenous expression of
      copine-III and enhanced the susceptibility of MHCC97-H cells to sorafenib: the
      IC50 value decreased from 1.15+/-0.11 to 0.25+/-0.05 MUmol/L. Moreover, silencing
      copine-III enhanced the effect of sorafenib on apoptosis, in vitro
      invasion/migration, and subcutaneous or intrahepatic growth of MHCC97-H cells in
      nude mice. Conclusion: Copine-III is a novel potential indicator of prognosis for
      patients who received sorafenib for advanced HCC treatment.

PMID- 30214301
TI  - A mono-carbonyl analog of curcumin induces apoptosis in drug-resistant EGFR
      mutant lung cancer through the generation of oxidative stress and mitochondrial
      dysfunction.
AB  - Introduction: Targeted therapies using epidermal growth factor receptor-tyrosine
      kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of non-small cell
      lung cancer (NSCLC) patients harboring EGFR mutations, leading to the approval of
      gefitinib and erlotinib as standard first-line clinical treatment. Inevitably, a
      considerable proportion of patients develop resistance to EGFR-TKIs due to the
      acquisition of secondary mutations within EGFR. Therefore, alternative strategies
      to target NSCLC are desperately needed. Materials and methods: In this study, we
      have evaluated the effect of a reactive oxygen species (ROS)-inducing agent WZ35,
      a mono-carbonyl analog of curcumin, to target an inherent biological property of
      cancer cells, increased oxidative stress. To study whether WZ35 can inhibit NSCLC
      tumorigenesis, we used gefitinib- and erlotinib-resistant cell line H1975.
      Results: In this study, we show that WZ35 treatment dramatically decreases cell
      viability and induces apoptosis in H1975 cells through the generation of ROS. We
      also found that the antitumor activity of WZ35 involved ROS-mediated activation
      of the endoplasmic reticulum stress pathway and mitochondrial dysfunction.
      Furthermore, WZ35 significantly inhibited H1975 xenograft tumor growth through
      the inhibition of cell proliferation and induction of apoptosis. Discussion:
      These findings show that WZ35 may be a promising candidate for the treatment of
      EGFR-TKI-resistant NSCLC.

PMID- 30214303
TI  - Predictive value of carcinoembryonic antigen and carbohydrate antigen 19-9
      related to downstaging to stage 0-I after neoadjuvant chemoradiotherapy in
      locally advanced rectal cancer.
AB  - Objective: To explore the value of carcinoembryonic antigen (CEA) and
      carbohydrate antigen 19-9 (CA19-9) in predicting downstaging to stage 0-I cancer
      after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer.
      Materials and methods: We respectively investigated pretreatment CEA,
      pretreatment CA19-9, posttreatment CEA, posttreatment CA19-9, pre-post-CA19-9
      ratio, and pre-post-CEA ratio in 674 patients with locally advanced rectal cancer
      receiving nCRT and determined the patients' thresholds by using the receiver
      operating characteristic curve analysis. The association between downstaging
      (stage 0-I after nCRT), pathological complete response, and clinicopathological
      parameters was evaluated using the Pearson chi2 test. The clinicopathological
      parameters which were found to be significantly associated with downstaging were
      analyzed by logistic regression models and were incorporated into a scoring
      system. Results: Multivariate analysis showed that pretreatment CA19-9 level,
      posttreatment CEA level, pre-post-CEA ratio, and pre-post-CA19-9 ratio were
      significantly correlated with downstaging. Area under the curve of the scoring
      system was higher than that of parameters alone. Conclusion: The 4-factor scoring
      system with CA19-9 level, posttreatment CEA level, pre- post-CEA ratio, and pre
      post-CA19-9 ratio is of more value in predicting downstaging to stage 0-I
      patients with locally advanced rectal cancer after nCRT than using the parameters
      alone.

PMID- 30214302
TI  - Clinical utility of fulvestrant in the treatment of breast cancer: a report on
      the emerging clinical evidence.
AB  - Fulvestrant is the first selective estrogen receptor (ER) downregulator available
      in clinical practice. It is a pure antiestrogen with no agonistic effects,
      leading to degradation of ER alpha, with activity in tamoxifen-resistant breast
      cancer (BC) models. Pharmacokinetic and pharmacodynamic studies and several
      postmarketing clinical trials led to the definition of the optimal dose at 500 mg
      intramuscularly on days 1, 15, and 29 and then every 28 days. Targeting ER alpha,
      fulvestrant is a cornerstone of treatment in luminal BCs, whose growth is largely
      driven by the ER pathway. In endocrine therapy-naive patients with hormone
      receptor-positive, HER2- advanced BC (ABC), fulvestrant yielded significantly
      longer progression-free survival compared to anastrozole in the Phase III FALCON
      study. Due to its mechanism of action and pharmacokinetic properties, fulvestrant
      is an ideal backbone for combination therapies. Preclinical studies have shown
      synergism with drugs acting on signaling pathways involved in the development of
      endocrine resistance, among which the cyclin D/cyclin-dependent kinase 4
      6/retinoblastoma pathway and the phosphatidylinositol 3-kinase
      (PI3K)/Akt/mammalian target of rapamycin pathway, contributing to overcoming or
      delaying endocrine resistance. In the Phase III PALOMA-3 trial, a combination of
      the cyclin-dependent kinase 4/6 inhibitor palbociclib with fulvestrant
      significantly improved progression-free survival over fulvestrant alone in women
      with hormone receptor positive, HER2- ABC progressing during prior endocrine
      therapy. This led to approval of the combination in this clinical setting.
      Similar results were obtained with abemaciclib and ribociclib. Combination with
      pan-PI3K inhibitors, though showing some efficacy, was hampered by the toxicity
      of these agents, and studies in combinations with more selective inhibitors of
      the alpha-catalytic subunit of PI3K are ongoing. Fulvestrant has shown partial
      activity also in patients with tumors harboring mutations of the ESR1 gene. It is
      thus a key drug in the treatment of ABC, whose role in combination with new
      targeted agents is still evolving.

PMID- 30214304
TI  - Probe-based three-dimensional confocal laser endomicroscopy of brain tumors:
      technical note.
AB  - Background: Confocal laser endomicroscopy (CLE) is used during fluorescence
      guided brain tumor surgery for intraoperative microscopy of tumor tissue with
      cellular resolution. CLE could augment and expedite intraoperative decision
      making and potentially aid in diagnosis and removal of tumor tissue. Objective:
      To describe an extension of CLE imaging modality that produces Z-stack images and
      three-dimensional (3D) pseudocolored volumetric images. Materials and methods:
      Hand-held probe-based CLE was used to collect images from GL261-luc2 gliomas in
      C57BL/6 mice and from human brain tumor biopsies. The mice were injected with
      fluorescein sodium (FNa) before imaging. Patients received FNa intraoperatively,
      and biopsies were imaged immediately in the operating room. Some specimens were
      counterstained with acridine orange, acriflavine, or Hoechst and imaged on a
      benchtop confocal microscope. CLE images at various depths were acquired
      automatically, compiled, rendered into 3D volumes using Fiji software and
      reviewed by a neuropathologist and neurosurgeons. Results: CLE imaging, Z-stack
      acquisition, and 3D image rendering were performed using 19 mouse gliomas and 31
      human tumors, including meningiomas, gliomas, and pituitary adenomas. Volumetric
      images and Z-stacks provided additional information about fluorescence signal
      distribution, cytoarchitecture, and the course of abnormal vasculature.
      Conclusion: 3D and Z-stack CLE imaging is a unique new option for live
      intraoperative endomicroscopy of brain tumors. The 3D images afford an increased
      spatial understanding of tumor cellular architecture and visualization of related
      structures compared with two-dimensional images. Future application of specific
      fluorescent probes could benefit from this rapid in vivo imaging technology for
      interrogation of brain tumor tissue.

PMID- 30214305
TI  - Prognostic value of serum alkaline phosphatase in the survival of prostate
      cancer: evidence from a meta-analysis.
AB  - Background: Many studies have evaluated the relationship between alkaline
      phosphatase (ALP) and the prognosis for prostate cancer (PCa). But they have not
      reached a widespread consensus yet. Therefore, we completed a meta-analysis to
      ascertain the significance of ALP and the prognosis for PCa. Methods: A
      literature search was performed in the PubMed, Embase, and Web of Science
      databases. HRs concerning overall survival (OS), progression-free survival (PFS),
      and cancer-specific survival (CSS) were extracted to evaluate the impacts of ALP
      on the prognosis for PCa. Subgroup analyses were conducted on different study
      types, regions, sample sizes, and cutoff values. Sensitivity analysis was
      performed by removing one study in sequence. Results: A total of 63 studies from
      54 articles with 16,135 patients were included in this meta-analysis. The pooled
      results indicated that high baseline ALP was associated with obviously poor OS
      (HR=1.74, 95% CI: 1.47-2.06) and PFS (HR=1.60, 95% CI: 1.13-2.26) in patients
      with PCa. The pooled HR for bone-specific ALP and OS was 1.76 (95% CI: 1.45
      2.15). However, no association between ALP and CSS (HR=1.002, 95% CI: 0.998
      1.005) was found for PCa. The results of subgroup analyses were all in accordance
      with the main findings. Sensitivity analysis suggested that no single study could
      affect the stability of the results. Conclusion: High serum ALP is significantly
      associated with poor OS and PFS except for CSS in PCa. ALP is an efficient and
      convenient biomarker for PCa prognosis.

PMID- 30214306
TI  - Association between lncRNA CASC8 polymorphisms and the risk of cancer: a meta
      analysis.
AB  - Objective: To explore the relationship between single-nucleotide polymorphisms
      (SNPs) in one of the long noncoding RNA (lncRNA), cancer susceptibility candidate
      8 (CASC8) gene and the risk of cancer. Materials and methods: A meta-analysis was
      conducted to summarize the relationship between common SNPs (rs10505477 and
      rs7837328) in the lncRNA CASC8 gene and the risk of cancer. The relevant
      references were retrieved from several authoritative databases. Rigorous
      inclusion and exclusion criteria were adopted to ensure the credibility of the
      results. The fixed effects or random effects model was used to calculate the OR
      and 95% CI. We tested for publication bias. Results: Fifteen articles containing
      20 datasets (24,504 cases and 22,969 controls) were finally included in the meta
      analysis. Compared to the individuals carrying the rs10505477 TT genotype, those
      with the TC or CC genotype had a decreased risk of cancer (TC vs TT: OR 0.876,
      95% CI 0.832-0.923, P<0.001; CC vs TT: OR 0.748, 95% CI 0.703-0.795, P<0.001).
      Allele C of rs10505477 might be a protective factor for decreasing susceptibility
      to cancer (OR 0.866, 95% CI 0.840-0.893, P<0.001). As for rs7837328, the GA and
      AA genotypes were associated with increased risks of cancer as compared to the GG
      genotype (ORs 1.209 and 1.336; 95% CIs 1.127-1.298 and 1.202-1.484,
      respectively); its A allele could significantly increase the risk of cancer
      compared with the G allele (OR 1.169, 95% CI 1.114-1.227, P<0.001). Conclusion:
      The rs10505477 and rs7837328 polymorphisms might be associated with risk of
      cancer.

PMID- 30214307
TI  - Methyl jasmonate enhances the radiation sensitivity of esophageal carcinoma cells
      by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3.
AB  - Purpose: In our previous study, we found that AKR1C3 was a radioresistance gene
      in KY170R cells. Downregulating the expression of AKR1C3 could enhance the
      radiosensitivity of esophageal carcinoma cells. In this study, we investigated
      whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1
      member C3 (AKR1C3), could overcome radiation resistance in AKR1C3 highly
      expressed cells. Patients and methods: We used clone formation assays to detect
      radiosensitivity effects. Flow cytometry assays were used to detect reactive
      oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent
      assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2)
      and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western
      blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor
      gamma (PPARgamma) expression. Results: We found that AKR1C3 was highly expressed
      in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of
      AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells
      expressing high levels of AKR1C3 (P<0.05). MeJ could inhibit the 11
      ketoprostaglandin reductase activity of AKR1C3 in a dose-dependent manner in
      KY170R cells. Incubation of KY170R cells with 200 umol/L of MeJ for 24 h reduced
      the expression of PGF2 by roughly 30% (P<0.05). The PPAR pathway inhibitor GW9662
      prevented the radiation sensitivity enhancement imparted by MeJ. After adding
      GW9662, there were no significant differences between the radiation sensitivities
      of MeJ-treated and -untreated KY170R cells (P>0.05). The radiation sensitivity
      effect of MeJ also depended upon the generation of ROS in KY170R cells; 48 h
      after irradiation, ROS levels in the MeJ group was twofold higher than in the
      untreated KY170R cells (P<0.05). The ROS scavenger, N-acetyl cysteine, could
      reverse the radiosensitivity effects of MeJ (P>0.05). Conclusion: Our results
      indicate that MeJ can increase the radiation sensitivity of AKR1C3-overexpressing
      KY170R cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3
      and increasing cellular ROS levels.

PMID- 30214308
TI  - ZNF259 promotes breast cancer cells invasion and migration via ERK/GSK3beta/snail
      signaling.
AB  - Purpose: Zinc finger protein 259 (ZNF259), also known as ZPR1, is a zinc finger
      containing protein that can bind the intracellular tyrosine kinase domain of
      EGFR. At present, our knowledge on ZNF259 in cancers is limited. Here, we aimed
      to explore the biological functions of ZNF259 in breast cancer and reveal their
      mechanisms. Patients and methods: The expression of ZNF259 was measured in 133
      cases of breast cancer by immunohistochemistry. The online database Kaplan-Meier
      (KM) Plotter Online Tool was used to analyze the relationship between ZNF259
      expression and breast cancer patient survival prognosis. Plasmid transfection and
      small interfering RNA and inhibitor treatments were carried out to explore the
      functions of ZNF259 in breast cancer cell lines and its potential mechanism.
      Matrigel invasion and wound healing assays were performed to detect the invasion
      and migration ability of cancer cells. In addition, protein expressions in
      tissues and cells were determined by Western blotting. Results: ZNF259 expression
      was much higher in breast cancer cells than in the adjacent normal breast duct
      glandular epithelial cells (75.94% vs 7.52%, P<0.001) and was closely related to
      the breast cancer patients' TNM stages (P=0.013) and lymph node metastasis
      (P=0.021). Knockdown of ZNF259 could downregulate p-ERK, p-GSK3beta, and Snail
      expression, and upregulate the expression of E-cadherin and ZO-1, and then it
      also inhibited invasion and migration by the breast cancer cell lines MCF-7 and
      MDA-MB-231. Correspondingly, ZNF259 transfection could upregulate p-ERK, p
      GSK3beta, and Snail expression, and downregulate E-cadherin and ZO-1 expression,
      which led to stronger invasion and migration abilities of cancer cells.
      Furthermore, the ERK inhibitor U0126 could reverse all these effects induced by
      ZNF259 transfection. Conclusion: ZNF259 could promote breast cancer cell invasion
      and migration by activating the ERK/GSK3beta/Snail signaling pathway.

PMID- 30214309
TI  - Prognostic value of tumor burden in nasopharyngeal carcinoma.
AB  - Background: The prognostic value of primary tumor volume (TV) in nasopharyngeal
      carcinoma (NPC) has been confirmed. However, studies of the prognosis value of
      tumor burden, including TV and nodal volume (NV), have been relatively
      infrequent. Therefore, the aim of this study was to evaluate the prognostic value
      of tumor burden in NPC patients treated with intensity-modulated radiotherapy.
      Methods: Receiver operating characteristics curves were generated to determine
      rational cutoff points for TV and NV. The volumes identified included 12.5, 25.0,
      and 50.0 mL, and 0, 12.5, and 25 mL, respectively. According to these cutoff
      volumes, four subgroups were established for TV as TV1-TV4, and four subgroups
      were established for NV as NV0-NV3. Then, the entire cohort (992 NPC patients)
      was divided into 16 subgroups according to these four levels of TV and NV. Based
      on similarities in the 5-year overall survival (OS) rates for these 16 subgroups,
      four patient groups were established, G1-G4. Results: The mean TV and NV values
      for our cohort were 39.5+/-30.8 mL and 16.5+/-17.6 mL, respectively. The 5-year
      distant failure-free rate, the 5-year disease-free survival rate, and the 5-year
      OS rate for G3 and G4 were significantly lower than those for G1 and G2. In
      particular, the OS curves of the four patient groups were significantly
      separated. A multivariate analysis identified TV >50 mL, T-stage (3-4), and N
      stage (2-3) as adverse prognostic factors for OS. Conclusions: The results of
      this study demonstrate that tumor burden has a significant prognostic value for
      NPC patients treated with intensity-modulated radiotherapy. Hence, tumor burden,
      including TV and NV, should be incorporated into the current staging system for
      NPC to improve prognostic significance.

PMID- 30214310
TI  - Trend in relative survival in squamous cervical cancer by decade from 1983 to
      2012: a period analysis.
AB  - Objective: Squamous cervical cancer (SCC), the predominant histological type,
      represents approximately 75-80% of all cervical cancers. Although the overall
      incidence of cervical cancer has declined worldwide, the data describing the
      changes in the incidence and long-term survival in SCC remain limited. Methods:
      The data were extracted from Surveillance, Epidemiology, and End Results (SEER)
      registries for an evaluation of the changes in the incidence and survival
      associated with SCC during 1983-2012. In addition, the patients with SCC were
      stratified by age, race, and socioeconomic status (SES). Stata 12.0 software was
      used to perform the Cox regression and Spearman's rank correlation analyses.
      Results: The overall incidence of SCC constantly declined from 7.3 to 5.6 to 4.3
      per 100,000 people; the peak age of incidence was 55-69 years in the first
      decade, while the 40-54 age group served as another incidence peak in the last 2
      decades. Median survival increased from 189 months to 231 months in the first 2
      decades and was not reached in the third decade. The 10-year relative survival
      rates (RSRs) changed from 63.2% to 66.5% to 62.1% across the 3 decades.
      Additionally, the survival gaps narrowed from 13% to 8% between Whites and Blacks
      and from 5.4% to 3.5% between low- and medium-poverty groups in the 3 decades.
      Conclusion: This study demonstrated a declining incidence over the 3 decades with
      an improvement in median survival. However, the relative survival associated with
      SCC did not improve in the last decade. Furthermore, the survival gaps between
      races and various SESs significantly narrowed over the 3 decades.

PMID- 30214311
TI  - Selective serotonin reuptake inhibitor use and mortality, postoperative
      complications, and quality of care in hip fracture patients: a Danish nationwide
      cohort study.
AB  - Purpose: To examine the association between selective serotonin reuptake
      inhibitor (SSRI) use and mortality, postoperative complications, and quality of
      in-hospital care in hip fracture patients. Patients and methods: The study was a
      nationwide cohort study based on individual-level linked, prospectively collected
      data from Danish population-based national registries covering all hospitals in
      Denmark. The health care system in Denmark is tax-funded, and all citizens have
      equal access to health care services. We included patients with first-time
      hospitalization due to hip fracture undergoing surgery from 2006-2016. We
      estimated the risk of 30-day mortality, any unplanned readmission, any
      reoperation, specific postoperative complications including cardiovascular events
      and major bleeding, and quality of in-hospital care using Cox and Poisson
      regression analyses comparing current and former SSRI users with non-users.
      Results: In 68,487 hip fracture patients, 13,272 (19%) were current SSRI users,
      2,777 (4%) were former SSRI users, and 52,438 (77%) were SSRI non-users. The 30
      day mortality risk was 13% in current SSRI users (HR 1.16, 1.10-1.21) and 12% in
      former (HR 1.15, 1.04-1.27) compared with 10% in non-users. The HR for any
      unplanned readmission was 1.11 (1.02-1.20) in current and 1.13 (1.01-1.27) in
      former SSRI users and for any reoperation 1.21 (1.11-1.31) in current and 1.04
      (0.84-1.28) in former SSRI users compared with non-users. The risk of venous
      thromboembolism, myocardial infarction, stroke, and bleeding were similar
      irrespective of SSRI use. No association between current and former SSRI use and
      quality of in-hospital care was found. Conclusion: In patients undergoing hip
      fracture surgery, 30-day mortality and overall readmission risk were elevated in
      both current and former SSRI users compared with non-users. Those currently using
      SSRI had a 26% increased reoperation risk compared with non-users. However, SSRI
      use was not associated with increased risk of other postoperative complications
      and lower quality of in-hospital care. A limitation of this study was the
      inability to control for potential confounding of social deprivation.

PMID- 30214312
TI  - Mental health, psychotropic medication use, and menstrual cycle characteristics.
AB  - Purpose: To examine the influence of depressive symptoms, perceived stress, and
      psychotropic medication use on prospectively assessed menstrual cycle regularity
      and length. Participants and methods: Data were obtained from Pregnancy Study
      Online, a prospective cohort study of pregnancy planners from North America. At
      baseline, women reported information on demographics, anthropometrics, lifestyle,
      and medical history, including their use of psychotropic medications. They also
      completed the Major Depression Inventory and the Perceived Stress Scale. Every 8
      weeks for up to 12 months or until conception, women completed follow-up
      questionnaires to assess changes in psychotropic medication use, perceived
      stress, and menstrual cycle characteristics (ie, cycle regularity and length).
      Women who completed at least one follow-up questionnaire from 2013 to 2018
      (n=3,346) were included in the primary analyses. A total of 5,439 women were
      included in secondary analyses utilizing baseline data only. Primary analyses
      estimated prevalence ratios (PR) and 95% CIs using log-binomial regression
      models. Results: Women with severe depressive symptoms at baseline, regardless of
      psychotropic medication use, had an 80% greater prevalence of irregular cycles
      during follow-up than women with no or low depressive symptoms (PR =1.80, 95% CI
      =1.48-2.19). Perceived stress was also associated with the prevalence of
      irregular cycles during follow-up (PR =1.33, 95% CI =1.14-1.55). Psychotropic
      medication use was not appreciably associated with menstrual characteristics
      after controlling for history of diagnosed depression and/or anxiety. Depressive
      symptoms, perceived stress, and psychotropic medication use showed little
      association with menstrual cycle length. Conclusion: Higher levels of depressive
      symptoms and perceived stress were associated with irregular menstrual cycles,
      but not appreciably associated with menstrual cycle length. Use of psychotropic
      medications was not meaningfully associated with cycle regularity or length.

PMID- 30214313
TI  - Risk of pneumonia in patients with burn injury: a population-based cohort study.
AB  - Background: Burns are the main cause of accidental injury, and pneumonia is a
      common respiratory disease in humans. Aim: The purpose of this study was to
      investigate the relationship between burn injury and pneumonia. Patients and
      methods: A nationwide population-based cohort study was conducted using data from
      the National Health Insurance Research Database in Taiwan. We identified and
      enrolled 2,893 subjects with burn injury, who were individually matched to 2,893
      subjects in the comparison group by using the propensity score. Furthermore, we
      used a self-controlled case-series design to estimate the temporal association
      between burn injury and pneumonia. Results: Exposure to burn injury revealed a
      higher risk of pneumonia than that to non-burn injury within 1 year. The Cox
      proportional hazards model revealed that, compared with the non-burn injury, burn
      injury yielded a 2.39-fold (95% CI=1.44-3.96) increase in risk of pneumonia. The
      exposure period of burn injury within 30 days showed 2.76-fold increase in risk
      of pneumonia (95% CI=1.44-3.96) compared with that in the baseline period.
      Conclusion: Burn injury was associated with a significant increased risk of
      pneumonia, especially occurring within 30 days.

PMID- 30214314
TI  - Demographic shift disproportionately increases cancer burden in an aging nation:
      current and expected incidence and mortality in Hungary up to 2030.
AB  - Background: Population aging is a common demographic pattern in developed
      countries, and aging increases the risk of cancer. The disproportionately high
      cancer burden, as a consequence, is especially pronounced in Central and Eastern
      European countries, including Hungary. Methods: We summarized current and
      projected future cancer incidences and mortalities utilizing data from the last
      two decades. Predictions are based on cancer incidence and mortality collected
      between 1996 and 2015 in Hungary. In addition to the crude rates, data were age
      standardized to the European standard population (ESP) of 2013, ESP of 1976, and
      local census of 2011. Results: The lifetime probability of developing cancer and
      cancer-related mortality has already reached 56.9% and 27.6% in men,
      respectively, and 51.9% and 21.7% in women. Between 2016 and 2030, the total
      population is expected to shrink by 6%, while the number of 60-year olds and
      above will grow by 18%. This will lead to a 35% increase in cancer incidence and
      30% increase in cancer death among 65-85-year olds. Joinpoint regression
      identified the period 2007-2015 as starting point for this coming increase in new
      cases. In women, lung and breast cancer will increase yearly by 1.9% and 1.7%,
      respectively, between 2016 and 2030, while in men, the prostate and colorectal
      cancer rates will increase yearly by 3.6% and 2.1%. Conclusion: In the aging
      population of Hungary, cancer incidence will increase considerably over previous
      projections. Although a large portion of the most rapidly rising cancers are
      avoidable by implementing public health programs, a substantial portion remains
      inevitably incurable.

PMID- 30214315
TI  - Comparative performance of a modified landmark approach when no time of treatment
      data are available within oncological databases: exemplary cohort study among
      resected pancreatic cancer patients.
AB  - Purpose: The Mantel-Byar method is the gold standard analytical approach to avoid
      immortal time bias, but requires information on the time between start of follow
      up and exposure initiation. Alternatively, a modified landmark approach might be
      used to mitigate the amount of immortal time bias, which assumes exposure
      initiation at a predefined landmark time. In the context of an expected positive
      association between adjuvant chemotherapy (ACT) and overall survival among
      resected pancreatic cancer (PCa) patients, this study aims to empirically assess
      the performance of this approach relative to the Mantel-Byar method. Patients and
      methods: Data from resected PCa patients diagnosed between 2003 and 2014 and
      registered in the national cancer registries of Belgium, the Netherlands, and
      Slovenia were used to estimate the association between ACT and overall survival
      using a Cox proportional hazards model by country and overall. Results derived
      from the immortal time bias (misclassifying the time to ACT initiation), Mantel
      Byar method, and conventional and modified landmark analyses with assumed cutoff
      times of ACT initiation at 9, 12 and 15 weeks post-diagnosis were compared.
      Results: In total, 5,668 patients with a total of 10,921 person-years of follow
      up were eligible. All analytical approaches showed a significant survival benefit
      for resected PCa patients who received ACT, but immortal time bias analyses led
      to strong overestimation of ACT benefits compared to the Mantel-Byar method
      (immortal time bias: overall HR [95% CI] 0.68 [0.62-0.75] vs Mantel-Byar method:
      0.82 [0.71-0.93]), whereas the conventional landmark approach generally provided
      rather conservative estimates (0.86 [0.75-1.00], 15 weeks landmark). HRs derived
      from modified landmark analyses depended on the cutoff time, but were similar
      compared to the Mantel-Byar method at 15 weeks (0.81 [0.70-0.94]). Conclusion: A
      modified landmark approach might be a valid alternative to the Mantel-Byar method
      if no time of treatment information is available. The performance depends on the
      chosen cutoff time.

PMID- 30214317
TI  - Elementary school staff knowledge about management of traumatic dental injuries.
AB  - Aim: This study investigated the knowledge of elementary school staff regarding
      the management of traumatic dental injuries (TDIs) in children. Methods: The
      present cross-sectional study analyzed data collected between September 2016 and
      April 2017. The sample consisted of 2,027 elementary school staff members in
      Riyadh, Saudi Arabia. A stratified cluster random sampling technique was used to
      select the required sample. Those who agreed to participate in the study
      completed a 4-part self-administered questionnaire comprising questions regarding
      demographic data, knowledge on management of tooth fracture, and avulsion using
      photographs of TDI cases. Results: The majority of the school staff showed
      inadequate basic knowledge regarding the importance of saving the broken piece of
      the tooth and identifying the tooth involved in the trauma (67% and 66.3%,
      respectively), P<0.05. However, they had a significantly high number of correct
      responses regarding the immediate management of TDIs for the 2 case scenarios
      presented in the questionnaire (P<0.05), and the majority (41%) reported normal
      saline as a suitable storage medium (P<0.01). Conclusion: This study revealed a
      lack of knowledge in certain aspects of TDIs among elementary school staff.

PMID- 30214316
TI  - Effect of opioid-substitution therapy and mental health counseling on HIV risk
      among hepatitis C-infected individuals.
AB  - Background: Understanding differences in HIV incidence among people living with
      hepatitis C virus (HCV) can help inform strategies to prevent HIV infection. We
      estimated the time to HIV diagnosis among HCV-positive individuals and evaluated
      factors that could affect HIV-infection risk in this population. Patients and
      methods: The British Columbia Hepatitis Testers Cohort includes all BC residents
      (~1.5 million: about a third of all residents) tested for HCV and HIV from 1990
      to 2013 and is linked to administrative health care and mortality data. All HCV
      positive and HIV-negative individuals were followed to measure time to HIV
      acquisition (positive test) and identify factors associated with HIV acquisition.
      Adjusted HRs (aHRs) were estimated using Cox proportional-hazard regression.
      Results: Of 36,077 HCV-positive individuals, 2,169 (6%) acquired HIV over 266,883
      years of follow-up (overall incidence of 8.1 per 1,000 person years). Overall
      median (IQR) time to HIV infection was 3.87 (6.06) years. In Cox regression,
      injection-drug use (aHR 1.47, 95% CI 1.33-1.63), HBV infection (aHR 1.34, 95% CI
      1.16-1.55), and being a man who has sex with men (aHR 2.78, 95% CI 2.14-3.61)
      were associated with higher risk of HIV infection. Opioid-substitution therapy
      (OST) (aHR 0.59, 95% CI 0.52-0.67) and mental health counseling (aHR 0.48, 95% CI
      0.43-0.53) were associated with lower risk of HIV infection. Conclusion:
      Injection-drug use, HBV coinfection, and being a man who has sex with men were
      associated with increased HIV risk and engagement in OST and mental health
      counseling were associated with reduced HIV risk among HCV-positive individuals.
      Improving access to OST and mental health services could prevent transmission of
      HIV and other blood-borne infections, especially in settings where access is
      limited.

PMID- 30214318
TI  - Prevention of gestational diabetes with a prepregnancy lifestyle intervention -
      findings from a randomized controlled trial.
AB  - Purpose: Lifestyle intervention studies performed during pregnancy have shown
      inconsistent results in relation to prevention of gestational diabetes mellitus
      (GDM). Therefore, the aim of this study was to assess the effect of an
      intervention initiated already before pregnancy in prevention of GDM in high-risk
      women. Patients and methods: A randomized controlled trial was conducted in four
      Finnish maternity hospitals between the years 2008 and 2014. Altogether 228 high
      risk women planning pregnancy were randomized to an intervention (n=116) or a
      control group (n=112). The risk factors were body mass index >=30 kg/m2 (n=46),
      prior GDM (n=120), or both (n=62), without manifest diabetes at study inclusion.
      Trained study nurses provided individualized lifestyle counseling every 3 months
      in addition to a group session with a dietician. The control group received
      standard antenatal care. GDM was defined as one or more pathological glucose
      values in a 75 g 2-hour oral glucose tolerance test, performed between 12 and 16
      weeks of gestation and if normal repeated between 24 and 28 weeks of gestation.
      Results: Within 12 months, 67% of the women (n=72) in the intervention group and
      63% of the women (n=71) in the control group (p=0.84) became pregnant. The
      cumulative incidence of GDM among the women available for the final analyses was
      60% (n=39/65) in the intervention group and 54% (n=34/63) in the control group
      (p=0.49). GDM was diagnosed already before 20 weeks of gestation in 60% (n=44/73)
      of the cases. Conclusion: The preconceptional lifestyle intervention applied in
      the present study did not reduce the incidence of GDM.

PMID- 30214319
TI  - Diet-induced vitamin D deficiency triggers inflammation and DNA damage profile in
      murine myometrium.
AB  - Background: Previously, we reported a significantly higher prevalence of uterine
      fibroids (UFs) in African American women. This minority group also commonly
      suffers from vitamin D deficiency. We have demonstrated that 1,25(OH)2D3 attains
      a fibroid growth inhibitory impact through its ability to block the G1/S (gap
      1/synthesis) phase of the cell cycle. Vitamin D is involved in DNA damage as well
      as in immune response regulation, anti-inflammation, autoimmunity and cancer.
      Since most of the prior data on vitamin D and UF were generated in vitro via
      established cell lines, it was necessary to verify and validate this observation
      in vivo using a diet-induced vitamin D-deficient mouse model. Materials and
      Methods: Our model of vitamin D lacking function was established using 8-week
      exposure of C57/BL6 mice to vitamin D-deficient diet provides evidence of
      different functions accomplished by vitamin D in the regulation of myometrium
      homeostasis disrupted in the context of uterine fibroid. Results: We found that
      vitamin D deficiency was associated with increased expression of sex steroid
      receptors in murine myometrium, increased expression of proliferation related
      genes, the promotion of fibrosis and enhanced inflammation, and promoted
      immunosuppression through Tregs expansion in murine myometrium. We also showed
      that a vitamin D deficient diet enhanced DNA damage in murine myometrium.
      Conclusion: Our model mimics the effects in humans that a lack of vitamin D has
      and propels the study of in vivo interaction between inflammation, genomic
      instability and cell proliferation in the myometrium.

PMID- 30214320
TI  - Implantation of toric intraocular lenses in patients with cataract and
      keratoconus: a case series.
AB  - Purpose: To describe the results of phacoemulsification and implantation of toric
      intraocular lenses (IOLs) in patients with cataract and keratoconus. Patients and
      methods: Prospective study of 4 patients (4 eyes) with cataract and keratoconus
      who underwent phacoemulsification with implantation of a toric IOL. Two different
      toric IOLs were used: AcrySof IQ SN6AT9 and AT Torbi 709M(P). Corneal tomography
      was performed preoperatively using Scheimpflug technique with Pentacam.
      Astigmatism was regular or slightly irregular in all patients. Postoperatively,
      best-corrected visual acuity (BCVA), astigmatism, spherical equivalent, and
      complications were recorded for all patients. Follow-up time was between 4 weeks
      and 7 months. Results: BCVA increased and astigmatism decreased in all patients.
      BCVA increased from 20/50 to 20/40 in patient 1, from 20/63 to 20/20 in patient
      2, from 20/40 to 20/32 in patient 3, and from hand motion to 20/40 in patient 4.
      Astigmatism decreased from -6.12 to -3.75 D in patient 1, from -4.62 to -1.75 D
      in patient 2, from -9.0 to -3.0 D in patient 3, and from -8.0 to -2.75 D in
      patient 4. One patient developed pseudophakic cystoid macular edema, but at last
      follow-up after 6 months the edema had resolved. Another patient developed
      posterior capsular opacification after 2 months. No misalignment of the axis of
      the IOL was observed. Conclusion: Correction of both astigmatism and cataract
      with phacoemulsification and implantation of a toric IOL can be an effective and
      safe choice for patients with cataract and keratoconus. However, predicting the
      refractive outcome in cataract surgery is difficult in patients with keratoconus,
      and the surgeon should be aware of different sources of biometric errors and the
      possible consequences.

PMID- 30214321
TI  - Collagen fiber changes related to keratoconus with secondary corneal amyloidosis.
AB  - We describe the histological changes in the collagen fibers of a 50-year-old male
      who presented keratoconus with secondary corneal amyloidosis. Corneal tissue from
      the patient was obtained following a penetrating keratoplasty and was subjected
      to histochemical analysis using Masson's trichrome staining, Congo red staining,
      anti-lactoferrin antibody, and anti-transforming growth factor-beta-induced
      protein (TGFBIp) antibody. A Congo red-positive region was detected in the
      anterior half of the stroma in the center and inferior cornea. Although
      hemotoxylin and eosin staining revealed irregularity in the Congo red-positive
      region, other parts of the stroma did not show any abnormalities. Positive
      staining both by anti-TGFBIp and anti-lactoferrin antibodies was observed in the
      Congo red-positive region. Interestingly, all the layers of the corneal stroma,
      including the peripheral region, were positively stained by anti-TFGBIp antibody,
      even in the Congo red-negative area. Masson's trichrome staining also showed
      irregular staining throughout the corneal stroma, even outside of the Congo red
      positive region. Additionally, Bowman's layer, which consists of collagen type
      IV, was damaged. TGFBIp was strongly expressed and Masson's trichrome staining
      was reduced throughout the entire keratoconic stroma. The constant qualitative
      changes in keratoconic collagen fibers, along with the observed abnormality in
      the Bowman's membrane, might point to the pathogenesis of secondary corneal
      amyloidosis in keratoconus.

PMID- 30214322
TI  - Four-year outcomes after minimally invasive transiliac sacroiliac joint fusion
      with triangular titanium implants.
AB  - Background: Increasing long-term evidence supports the safety and effectiveness
      of minimally invasive sacroiliac joint fusion (SIJF) for sacroiliac joint (SIJ)
      dysfunction, an important cause of chronic low-back/buttock pain. Objective: To
      report 4-year follow-up in patients undergoing SIJF using triangular titanium
      implants (TTI) as part of two prospective trials. Methods: We enrolled 103
      subjects at 12 centers treated with TTI in two prospective clinical trials
      (NCT01640353 and NCT01681004) and followed them in the current study
      (NCT02270203), with clinic visits at 3, 4, and 5 years. Results: At 4 years, mean
      SIJ pain scores (available in 91 subjects [88.3%]) had decreased by 54 points
      from baseline; disability (Oswestry Disability Index) scores decreased by 26
      points; and quality of life (EuroQOL-5D) improved by 0.3 points (0-1 scale).
      Satisfaction rates were high and the proportion of subjects taking opioids
      decreased from 77% at baseline to 43% at 4-year follow-up. Conclusion: Four-year
      follow-up showed continued excellent responses in patients with SIJ pain treated
      with SIJF using triangular titanium implants.

PMID- 30214324
TI  - Conservative treatment of duodenal diverticulitis perforation: a case report and
      literature review.
AB  - Perforation is the rarest complication of the duodenal diverticulum (DD), but it
      is the most serious complication. Mortality rate was reported up to 30%, which
      may be related to diagnostic delay because the symptoms of the perforated DD are
      vague and nonspecific. Therefore, accurate diagnosis is important to improve the
      clinical outcome. Surgical treatment was considered as the standard therapeutic
      option. However, surgical intervention may increase morbidity and mortality due
      to surgical complications. Therefore, nonoperative management can be considered
      in some patients with perforated diverticulum who have stable vital signs without
      generalized peritonitis, or in elderly patients with comorbidities. Several case
      reports of nonoperative management of perforated DD have been reported. Herein,
      we describe a patient with perforated DD diagnosed based on a computed tomography
      scan, who was successfully treated with conservative treatment.

PMID- 30214323
TI  - Spotlight on the LinxTM Reflux Management System for the treatment of
      gastroesophageal reflux disease: evidence and research.
AB  - Background: The initial approach to gastroesophageal reflux disease (GERD)
      management typically involves lifestyle modification and medical therapy
      utilizing acid reducing agents such as histamine blockers and proton pump
      inhibitors. In severe cases refractory to such treatments, surgical therapy may
      be indicated. The gold standard for surgical treatment of GERD is the
      laparoscopic Nissen fundoplication. In recent years, a new technique known as
      magnetic sphincter augmentation (MSA) has been developed using the LinxTM Reflux
      Management System. This is an implantable ring of magnetic beads that is placed
      around the esophagus at the gastroesophageal junction to restore lower esophageal
      integrity. The aim of this review is to discuss the current literature regarding
      indications, surgical technique, efficacy, and complications of MSA using the
      Linx device. Methods: A standardized literature search was performed yielding 367
      abstracts. After elimination due to duplicates between databases and irrelevance,
      96 articles remained. The information found to be significant and non-redundant
      was included in this review. Conclusion: After several years of clinical
      application, the Linx device has been shown to not only be effective for the
      management of GERD but also be as effective as fundoplication. With respect to
      safety, the most common complication of MSA is dysphagia. This often resolved
      without intervention, but esophageal dilation or device explanation are
      occasionally necessary. Not fully appreciated in earlier reviews, erosion of the
      device into the esophagus appears to be the most significant complication of the
      device after extended follow-up. While very rare, the potentially severe
      consequences of this phenomenon suggest that the device should be used with some
      restraint and that patients should be made aware of this potential morbidity.
      Fortunately, in the few cases of device erosion described in the literature
      reviewed, the Linx device was easily and safely removed.

PMID- 30214325
TI  - Hepatitis C in Lebanon: the burden of the disease and the value of comprehensive
      screening and treatment.
AB  - Purpose: To analyze the hepatitis C virus (HCV) burden in Lebanon and the value
      of comprehensive screening and treatment for different age groups and fibrosis
      stages. Methods: We used a multicohort, health-state-transition model to project
      the number of HCV genotype 1 and 4 patients achieving a sustained virologic
      response 12 weeks after treatment or progressing to compensated cirrhosis (CC),
      decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver-related
      death (LrD) from 2016 to 2036. In the low/medium/high screening scenarios, the
      proportion of patients screened for HCV was projected to increase to 60%/85%/99%,
      respectively, by 2036. We analyzed four treatment strategies: 1) no treatment, 2)
      all-oral direct-acting antivirals (DAAs) given to F3-F4 (CC) patients only, 3)
      all-oral DAAs to F2-F3-F4 (CC) patients, and 4) all-oral DAAs to all fibrosis
      patients. Results: Low, medium, and high HCV screening scenarios projected that
      3,838, 5,665, and 7,669 individuals will be diagnosed with HCV infection,
      respectively, from 2016 to 2036, or 40% of those aged 18-39 years, and 60% of
      those aged 40-80 years. With no treatment, the projected number of patients
      reaching CC, DCC, HCC, or LrD in 2036 was 899, 147, 131, and 147, respectively,
      for the 18-39 years age group. For the 40-80 years age group, these projections
      were substantially greater: 2,828 CC, 736 DCC, 668 HCC, and 958 LrD. The overall
      economic burden without treatment reached 150 million EUR. However, introducing
      DAAs for F0-F4 patients was projected to increase the proportion of remaining
      life-years spent in sustained virologic response 12 weeks after treatment by 43%
      and 62% compared to DAAs given at F2-F4 or F3-F4 only, respectively. Conclusion:
      An enhanced screening policy combined with broader access to DAAs can diminish
      the future clinical and economic burden of HCV in the Lebanese population and,
      for the middle-aged and elderly, provide the greatest health benefit with net
      cost savings.

PMID- 30214326
TI  - Copeptin as a novel marker predicting prognosis of liver cirrhosis and its major
      complications.
AB  - Objectives: The aim of the work was to assess the level of copeptin as a
      surrogate marker predicting the severity of liver diseases and its major
      complications. Patients and methods: This was a cross-sectional study that
      included 40 patients and 10 controls and was performed in Tanta University
      Hospital between June 2016 and November 2016. The studied cases were divided into
      five groups: group I (10 patients): compensated cirrhosis; group II (10
      patients): cirrhosis with gastrointestinal hemorrhage due to portal hypertension;
      group III (10 patients): cirrhosis with hepatorenal syndrome; group IV (10
      patients): cirrhosis with liver cell failure; and group V (10 controls): normal
      healthy individuals. Results: Regarding serum copeptin in the studied groups,
      copeptin showed a significant decrease in group I vs group II' group I vs group
      III, and group I vs group IV; and there was a significant increase in group II vs
      group III' group II vs group IV' group II vs control' group III vs control, and
      group IV vs control. No significance was detected between group I vs control and
      group III vs group IV. Conclusions: Copeptin is a novel marker for the
      determination of prognosis of liver cirrhosis. There is significant association
      between serum level of copeptin and complications of liver cirrhosis.

PMID- 30214327
TI  - Macrophage activation syndrome: early diagnosis is key.
AB  - Macrophage activation syndrome (MAS) is a life-threatening condition, and it is a
      subset of hemophagocytic lymphohistiocytosis (HLH). The clinical features include
      a persistent high-grade fever, hepatosplenomegaly, lymphadenopathy, hemorrhagic
      manifestations, and a sepsis-like condition. From the clinical features, it is
      usually difficult to differentiate between a true sepsis, disease flare-ups, or
      MAS. Although the laboratory abnormalities are similar to those of a disseminated
      intravascular coagulation, which shows pancytopenia, coagulopathy,
      hypofibrinogenemia, and an elevated d-dimer test, it can also be a late stage of
      MAS. Currently, MAS is still underrecognized and usually results in delayed in
      diagnosis, which leads to high morbidity and mortality. This literature review
      was conducted in the context of the clinical manifestations and the laboratory
      abnormalities in MAS, which might provide some clues for an early diagnosis. The
      best ways for an early recognition and a satisfactory diagnosis were based on the
      relative changes in the overall parameters from the baseline, together with a
      thorough and continuous physical examination for these kinds of patients. At
      present, diagnostic criteria have been proposed for HLH, MAS-associated systemic
      juvenile idiopathic arthritis, and an MAS-associated systemic lupus
      erythematosus. Therefore, selecting the proper diagnostic criteria for use is
      essential because not all of the criteria are suitable for every autoimmune
      disease.

PMID- 30214328
TI  - Distinct psychopathology of patients who attempted suicide with rodenticide in
      Taiwan: a comparative study with patients of suicide with paraquat.
AB  - Objective: Rodenticide as a means of suicide has been documented for centuries.
      However, this method is often discussed in conjunction with other pesticides.
      Thus, we aimed to focus on patients who committed suicide with rodenticide and
      compared them with those who used paraquat for suicide, another frequently used
      yet lethal method, to highlight the different psychopathology of patients who
      choose rodenticide as their means of suicide. Methods: A 12-year retrospective
      chart review was conducted on the medical records of all patients admitted to
      Chang Gung Memorial Hospital due to attempted suicide by either rodenticide or
      paraquat. Psychiatric consultation sheets were collected to ascertain the
      psychiatric comorbidity and the major stressor for suicide, measured by the
      Social Readjustment Rating Scale. A chi2 test and logistic regression were used
      for group comparisons. Results: Seventeen rodenticide and 157 paraquat suicide
      attempts were identified. Compared with suicides by paraquat, suicides by
      rodenticide had a more even distribution in the gender ratio but a lower Social
      Readjustment Rating Scale score (p<0.001). Depressive disorder was the most
      common diagnosis in suicides by rodenticide and paraquat. However, schizophrenia
      and psychotic disorder (29.4%) was the second most common diagnosis and a
      significant predictor of suicide by rodenticide (odds ratio =9.21, 95% confidence
      interval =1.2-66.07, p=0.027). Conclusion: High comorbidity of psychosis in
      suicide by rodenticide warrants disease-specific suicide prevention and
      additional large-scale research to confirm this association.

PMID- 30214329
TI  - Effects of a group activity-based motivational enhancement therapy program on
      social media addictive behaviors among junior high school students in Thailand: a
      cluster randomized trial.
AB  - Purpose: This study aimed to assess the effects of a group activity-based
      motivational enhancement therapy (GA-MET) program on social media addictive
      behaviors among junior high school students. Materials and methods: This cluster
      randomized trial was performed in 245 junior high school students who used social
      media in the lower part of northeast Thailand. The GA-MET program group and the
      control group sessions lasted 8 weeks and were followed up 4 weeks later. The
      addictive social media behaviors, average duration of social media usage during
      weekdays and weekends (hours/day), child behaviors, self-esteem, and depression
      were investigated using a self-reported questionnaire. Multivariable linear
      regression was used to compare the mean and 95% CIs between two groups. Results:
      The GA-MET program significantly decreased the average duration of social media
      usage during weekdays and weekends (hours/day) (-1.27, 95% CI: -2.18,-0.37 and 
      1.25, 95% CI: -2.22, -0.29, respectively), emotional behavior (-0.69, 95% CI: 
      1.18, -0.19), and depression (-4.03, 95% CI: -6.07, -1.99) in the treated group
      compared to the control group. Conclusion: The GA-MET program could reduce the
      risk of social media addictive behaviors in junior high school students in
      Thailand by decreasing time spent on social media, emotional behaviors, and
      depression.

PMID- 30214330
TI  - Improving access to specialized care for first-episode psychosis: an ecological
      model.
AB  - Psychotic spectrum disorders are serious illnesses with symptoms that
      significantly impact functioning and quality of life. An accumulating body of
      literature has demonstrated that specialized treatments that are offered early
      after symptom onset are disproportionately more effective in managing symptoms
      and improving outcomes than when these same treatments are provided later in the
      course of illness. Specialized, multicomponent treatment packages are of
      particular importance, which are comprised of services offered as soon as
      possible after the onset of psychosis with the goal of addressing multiple care
      needs within a single care setting. As specialized programs continue to develop
      worldwide, it is crucial to consider how to increase access to such specialized
      services. In the current review, we utilize an ecological model of understanding
      barriers to care, with emphasis on understanding how individuals with first
      episode psychosis interact with and are influenced by a variety of systemic
      factors that impact help-seeking behaviors and engagement with treatment. Future
      work in this area will be important in understanding how to most effectively
      design and implement specialized care for individuals early in the course of a
      psychotic disorder.

PMID- 30214332
TI  - Health-related quality of life in patients with iron deficiency anemia: impact of
      treatment with intravenous iron.
AB  - Most physicians appear to be aware of the health consequences of advanced anemia,
      especially in the acute setting, frequently responding with a not inconsequential
      therapeutic default of transfusion. In contrast, the profound impact that chronic
      anemia, of any degree, may have on a patient's performance is underappreciated.
      The focus of this review is to 1) delineate the consistent and broad impact of
      anemia on patient quality of life as documented by multiple well-validated
      patient-reported outcome instruments and 2) demonstrate the essential
      normalization of the debilitation as assessed by these instruments following the
      administration of intravenous iron.

PMID- 30214333
TI  - Satisfied patients and pediatricians: a cross-sectional analysis.
AB  - Background: There is a lack of research in the USA comparing patient satisfaction
      with pediatricians and other primary care physicians (PCPs). We examined and
      compared patient satisfaction toward their pediatricians and PCPs and
      characterized factors associated with higher patient satisfaction in these two
      groups. Methods: A random coefficient model with random slope and intercept was
      fit to the data, with patient satisfaction as a function of pediatrician/PCP,
      covariates, and physician random effects. Effect heterogeneity was assessed by
      allowing slope to vary as a function of covariates. Mediation analysis using the
      random coefficient model was conducted to calculate average total effect, average
      natural direct effect, and average indirect effect of pediatrician/PCP on
      satisfaction mediated by waiting/visit times. Results: Pediatricians had higher
      predicted satisfaction ratings than PCPs (total effect = 4.8, 95% CI 3.7-5.9),
      with population-averaged mean of 82.2 (0.54) vs 77.4 (0.13). The direct effect
      was 3.9 (2.8-5.0) and the indirect effect was 0.9 (0.9-0.9), suggesting that part
      but not all of the total effect can be explained by pediatricians having
      decreased waiting/visit times leading to increased satisfaction. Predictions by
      subgroup suggested that pediatricians had lower ratings than PCPs for first
      visit, but higher ratings for all other covariate strata considered. Having
      longer waiting times and decreased visit times coincided with closer mean ratings
      between pediatricians and PCPs, other significant effect modifiers included
      patient sex, provider sex, and region of practice. Conclusion: Pediatricians
      scored higher patient satisfaction ratings than the combined group of other PCPs.
      Pediatricians had shorter wait times to see their patients compared to PCPs.
      Shorter wait times and longer visit times were associated with higher patient
      satisfaction ratings.

PMID- 30214334
TI  - Thalassemia minor presenting with vitamin B12 deficiency, paraparesis, and
      microcytosis.
AB  - Vitamin B12 is essential for proper neurological functioning, and its deficiency
      may cause a wide range of neuropsychiatric and hematological manifestations. We
      report a case of a previously healthy 32-year-old female who was admitted to our
      hospital with sudden onset of bilateral lower limb paraparesis and loss of
      sensation. The serum level of vitamin B12 was mildly decreased with high
      methylmalonic acid and homocysteine levels. However, her complete blood count
      showed no evidence of anemia or macrocytosis; instead, her mean corpuscular
      volume was low. Hemoglobin electrophoresis showed thalassemia trait, and that
      probably masked the megaloblastic features of vitamin B12 deficiency. She
      responded fully to vitamin B12 replacement therapy.

PMID- 30214331
TI  - Role of normal sleep and sleep apnea in human memory processing.
AB  - A fundamental problem in the field of obstructive sleep apnea (OSA) and memory is
      that it has historically minimized the basic neurobiology of sleep's role in
      memory. Memory formation has been classically divided into phases of encoding,
      processing/consolidation, and retrieval. An abundance of evidence suggests that
      sleep plays a critical role specifically in the processing/consolidation phase,
      but may do so differentially for memories that were encoded using particular
      brain circuits. In this review, we discuss some of the more established evidence
      for sleep's function in the processing of declarative, spatial navigational,
      emotional, and motor/procedural memories and more emerging evidence highlighting
      sleep's importance in higher order functions such as probabilistic learning,
      transitive inference, and category/gist learning. Furthermore, we discuss sleep's
      capacity for memory augmentation through targeted/cued memory reactivation. OSA -
      by virtue of its associated sleep fragmentation, intermittent hypoxia, and
      potential brain structural effects - is well positioned to specifically impact
      the processing/consolidation phase, but testing this possibility requires
      experimental paradigms in which memory encoding and retrieval are separated by a
      period of sleep with and without the presence of OSA. We argue that such
      paradigms should focus on the specific types of memory tasks for which sleep has
      been shown to have a significant effect. We discuss the small number of studies
      in which this has been done, in which OSA nearly uniformly negatively impacts
      offline memory processing. When periods of offline processing are minimal or
      absent and do not contain sleep, as is the case in the broad literature on OSA
      and memory, the effects of OSA on memory are far less consistent.

PMID- 30214335
TI  - Effects of tDCS-like electrical stimulation on retinal ganglion cells.
AB  - Purpose: Transcranial direct current stimulation (tDCS) has been studied in
      humans for its effects on enhancement of learning, amelioration of psychiatric
      disorders, and modification of other behaviors for over 50 years. Typical
      treatments involve injecting 2 mA current through scalp electrodes for 20
      minutes, sometimes repeated weekly for two to five sessions. Little is known
      about the direct effects of tDCS at the neural circuit or the cellular level.
      This study assessed the effects of tDCS-like currents on the central nervous
      system by recording effects on retinal ganglion cell responsiveness using the
      rabbit retina eyecup preparation. Materials and methods: We examined changes in
      firing to On and Off light stimuli during and after brief applications of a range
      of currents and polarity and in different classes of ganglion cells. Results: The
      responses of Sustained cells were consistently suppressed during the first round
      of current application, but responses could be enhanced after subsequent rounds
      of stimulation. The observed first round suppression was independent of current
      polarity, amplitude, or number of trials. However, the light responses of
      Transient cells were more likely to be enhanced by negative currents and
      unaffected or suppressed by first round positive currents. Short-duration
      currents, that is, minutes, as low as 2.5 uA produced a remarkable persistency of
      firing changes, for up to 1.5 hours, after cessation of current. Conclusion: The
      results are consistent with postulated tDCS alteration of central nervous system
      function, which outlast the tDCS session and provide evidence for the isolated
      retina as a useful model to understand tDCS actions at the neuronal level.

PMID- 30214336
TI  - Evaluation of binocular function among pre- and early-presbyopes with asthenopia.
AB  - Purpose: Individuals approaching presbyopia may exhibit ocular symptoms as they
      contend with visual demands of near work, coupled with natural age-related
      changes in accommodation. Therefore, accommodation and vergence of 30- to 40-year
      old, myopic, soft contact lens wearing subjects with symptoms of asthenopia and
      no history of using multifocal lenses were evaluated. Patients and methods: In
      this prospective, observational study, 253 subjects with asthenopia were
      evaluated by 25 qualified practitioners, each at a different clinical site.
      Subjects were 30-40 years in age, had symptoms of soreness, eyestrain, tired
      eyes, or headaches with near work, regularly performed 2-3 consecutive hours of
      near work, and were undiagnosed with presbyopia. Amplitude of accommodation (AC)
      and near point convergence (NPC) were measured with a Royal Air Force binocular
      gauge. Triplicate push up and push down AC and NPC measures were recorded, and
      average AC values were compared to those calculated using the Hofstetter formula
      (HF). Results: The average AC push up/push down value was significantly better
      than the HF prediction for this age range (8.04+/-3.09 vs 6.23+/-0.80 D),
      although 22.5% of subjects had mean AC below their HF value (5.36+/-0.99 D). The
      average NPC push up/push down value was 12.0+/-4.69 cm. The mean binocular AC
      value using the push up measure was significantly better than the push down
      measure (8.5+/-3.4 vs 7.6+/-3.0 D). The mean NPC value using the push up measure
      was significantly worse than the push down measure (13.0+/-5.0 vs 11.0+/-4.7 cm).
      The most frequent primary diagnosis was ill-sustained accommodation (54%),
      followed by accommodative insufficiency (18%), and accommodative infacility
      (12%). Conclusion: Based upon a standardized assessment of accommodation and
      vergence, ill-sustained accommodation was the most frequent diagnosis among this
      population.

PMID- 30214337
TI  - Effects of relative negative spherical aberration in single vision contact lens
      visual performance.
AB  - Objective: The study aimed to compare the visual performance of contact lenses
      with and without negative spherical aberration (SA) over 5 days of wear. Methods:
      At baseline, 32 myopic participants (aged 18-33 years) were fitted in a
      randomized order with two lenses (test lens with minimal or no SA and 1-Day
      Acuvue Moist designed with negative SA) for 5 days (minimum 6 hours wear/day).
      Participants returned for a follow-up visit. This consisted of on-axis SA
      measurements; high- and low-contrast visual acuities at 6 m; high-contrast
      acuities at 70 and 40 cm; low-illumination, low-contrast acuity at 6 m;
      stereopsis at 40 cm; horizontal phorias at 3 m and 33 cm; and +/-2.00 D monocular
      accommodative facility at 33 cm. Participants also rated (1-10 scale) vision
      quality (clarity and lack of ghosting for distance, intermediate, near, driving
      vision and vision stability during day- and night-time), overall vision
      satisfaction, ocular comfort, and willingness to purchase (yes/no response).
      Results: 1-Day Acuvue Moist induced significantly (p<0.05) more negative SA at
      distance (Delta=0.078 MUm) and near (Delta=0.064 MUm) compared to the test lens,
      for a 6 mm pupil. There were no significant differences (p>0.05) in acuity,
      binocular vision, and all subjective metrics except vision stability between
      lenses where the test lens was rated to provide more stable vision (p<0.05).
      Conclusion: Contrary to expectations, incorporating negative SA in single vision
      soft contact lenses did not improve visual performance in non-presbyopic adult
      myopes.

PMID- 30214338
TI  - The prevalence of strabismus types in strabismic Iranian patients.
AB  - Purpose: To determine the frequency of different types of strabismus and
      amblyopia in the patients of strabismus clinics from 2008 to 2014. Methods: This
      retrospective cross-sectional study was conducted using data from the archives of
      Farabi Hospital in Tehran, Iran, from 2008 to 2014. The study consisted of using
      records of strabismic patients. From these, strabismus types and associated
      abnormalities, types of amblyopia and other ocular pathological findings were
      recorded. Results: In this study, 1174 strabismic patients were studied.
      Accommodative esotropia (ET) was the most prevalent type of strabismus accounting
      for 25.04% of all strabismic patients while intermittent exotropia (XT),
      nonaccommodative ET and partially accommodative ET, with 12.09%, 11.24% and
      10.39%, respectively, were relatively common. Also, 63.03% of all strabismic
      patients had esodeviation with XT coming second accounting for 24.53% of
      patients. Other ocular pathologic findings in addition to strabismus were found
      in 236 (20.1%) patients. The most common association with those types of
      strabismus was inferior oblique over action accounting for 11.07% of all cases,
      and 88 patients had nystagmus in addition to strabismus. Significantly 45% of
      patients had no amblyopia and 37% of patients had a combined type of amblyopia
      which was the most common type of amblyopia found in strabismic patients.
      Conclusion: The prevalence of ET was two and a half times more than XT and almost
      half of strabismic patients suffer from amblyopia. This study suggests that
      strabismus screening of children could be useful in the early detection of
      strabismus, appropriate management of it and prevention of strabismic amblyopia.

PMID- 30214339
TI  - Spotlight on fundus autofluorescence.
AB  - Fundus autofluorescence (FAF) imaging is based on the fluorescence from ocular
      endogenous fluorophores located in the retinal pigment epithelium and choroid,
      mainly lipofuscin and melanin. It is a noninvasive technique that provides
      information about the spatial distribution of lipofuscin/melanin and retinal
      pigment epithelium health status. An overview about the fluorophores responsible
      for FAF imaging and the usefulness of FAF imaging in the noninvasive assessment
      and monitoring of retinal diseases, such as age-related macular degeneration,
      diabetic retinopathy, diabetic macular edema, central serous chorioretinopthy,
      retinitis pigmentosa and retinal dystrophies, are discussed in this review.

PMID- 30214340
TI  - Investigating the effect of eye cosmetics on the tear film: current insights.
AB  - Eye cosmetics are frequently applied among female populations of all age groups
      around the world. However, the migration of cosmetic products across the eyelid
      margin has been reported, and this is thought to exacerbate tear film instability
      and symptoms of dry eye. Furthermore, numerous adverse effects and complications
      have also been reported with eye cosmetic wear, and the associated inflammatory
      responses may potentially increase the propensity toward ocular surface disease
      development. Prospective studies have demonstrated that eyeliner application at
      the inner eyelash line is associated with higher levels of tear film
      contamination and ocular discomfort than application at the outer periocular
      skin. A recent randomized trial also highlighted the potential for eye cosmetic
      wear to compromise the efficacy of lipid-based dry eye supplements. This review
      outlines the current evidence base and understanding regarding the periocular
      migration of eye cosmetic products, the effects of cosmetic product contamination
      on tear film function, and the use of dry eye treatments in eye cosmetic wearers.

PMID- 30214341
TI  - A 5-year retrospective record review of hospital-based low-vision rehabilitation
      in Thailand.
AB  - Purpose: To investigate the quality-of-life-related goals of low-vision patients,
      the causes of visual impairment, and the low-vision rehabilitation services at a
      Thai national tertiary referral center. Subjects and methods: A review was
      conducted on the medical records of patients attending the Low Vision
      Rehabilitation Clinic, Siriraj Hospital, Bangkok, Thailand, between 2012 and
      2016. Results: A total of 992 patient records were included, comprising of 760
      adults (aged over 15 years) and 232 children (aged <=15), with a mean age of 52.2
      and 5.4 years, respectively. The retina was the most common anatomic site of
      visual impairment. Among the adults, the most common ocular condition was
      retinitis pigmentosa (28.3%), followed by age-related macular degeneration
      (10.3%), glaucoma (10.0%), and diabetic retinopathy (9.6%). As for the children,
      the most common ocular conditions were cortical visual impairment (17.7%), optic
      nerve hypoplasia (13.4%), and retinopathy of prematurity (9.5%). More patients
      had low vision (a visual acuity of <6/18-3/60) than blindness (a visual acuity
      below 3/60). The most commonly stated goals among the adults were reading,
      writing, and performing near tasks (34.7%), and independent mobility (21.3%),
      whereas for children, the most frequently indicated goal was visual and
      developmental stimulation (38.4%). The services most often provided for the
      adults were the prescribing of visual aid devices (51.8%) and orientation and
      mobility training (40.7%), while the children most often received visual and
      developmental stimulation provided by a multidisciplinary team (33.8%). The Thai
      Government's Universal Health Care Coverage scheme was the most commonly used
      medical insurance. Conclusion: Data from this study can be used to improve low
      vision patient care and rehabilitation services, and as input to the further
      development of national health care policies for low-vision patients.

PMID- 30214342
TI  - Ocular dryness assessment in Saudi employees working indoors and outdoors.
AB  - Objective: To investigate dry eye disease in Saudi employees working in indoor
      and outdoor environments. Methods: A single-center randomized controlled study
      was carried out in an optometry clinic, to assess the ocular dryness of 24 male
      employees (12 indoor and 12 outdoor employees, mean age 36.4+/-2.5 years). The
      Ocular Surface Disease Index questionnaire was used to assess ocular dryness.
      Tear film assessment was carried out using phenol red thread (PRT), tear film
      osmolarity test, and fluorescein tears breakup time (FTBUT) with slit-lamp
      biomicroscopy. Results: Both indoor and outdoor employees showed mild-to-moderate
      ocular dryness. A significant difference (P=0.004) was found for the tear quality
      test (FTBUT) between the indoor (8.58+/-4.8) and outdoor (5.54+/-1.3) employees.
      However, no significant differences for the tear quantity tests (tear osmolarity
      and PRT) between the indoor and outdoor employees were observed. Conclusion: Dry
      eye cases were detected in both groups. This might be due to the hot dry
      environment in Riyadh and the use of air conditioners commonly used indoors. A
      significant difference was observed for the tear film stability, which might be
      due to the effect of environment and/or visual display unit use.

PMID- 30214343
TI  - Demodex blepharitis: clinical perspectives.
AB  - Demodex folliculorum and Demodex brevis are two mites which infest the human eye
      and which may, in excess, lead to a wide range of anterior segment findings.
      Demodex mites have been implicated in anterior and posterior blepharitis,
      blepharoconjunctivitis, blepharokeratitis, and beyond. Due to significant overlap
      with other anterior segment conditions, Demodex infestation remains
      underdiagnosed and undertreated. Definitive diagnosis can be made with lash
      sampling, and the most common mode of treatment is with tea tree oil in varying
      concentrations. This article summarizes elements of pathogenesis, diagnosis, and
      management critical to clinical care of this common condition.

PMID- 30214345
TI  - Strategies for improving the early diagnosis of keratoconus.
AB  - To diagnose keratoconus at its earliest stage is meaningful in order to avoid
      refractive surgery in the eye, which may lead to further damage in the abnormal
      cornea structure and consequently cause iatrogenic ectasia. In this article, the
      following aspects of detecting earliest stage of keratoconus were reviewed: 1)
      nomenclature of the earliest forms of keratoconus; 2) diagnosis of keratoconus
      using curvature-based topography (also known as Placido-based topography, ie,
      videokeratography) as a traditional method and elevation-based topography as a
      new method which has gained popularity in recent years; and 3) other methods
      analyzing keratoconus cornea like corneal biomechanics and wavefront sensing.
      Elevation-based topography using either Scheimpflug imaging techniques or slit
      scanning imaging techniques has shown to be advantageous over the curvature-based
      topography in detecting keratoconus at its earliest stage. Posterior elevation of
      the cornea is notified to enhance the sensitivity and specificity of detection if
      used along with the measurements of anterior surface of the cornea. Cornea
      biomechanics analysis and wavefront sensing also revealed differences between
      normal eyes and keratoconic eyes in their earliest stage. Combining the latest
      technology and the traditional techniques will be the future trend to improve
      early diagnosis of keratoconus.

PMID- 30214344
TI  - Contact lens associated microbial keratitis: practical considerations for the
      optometrist.
AB  - Microbial keratitis (MK) is a corneal condition that encompasses several
      different pathogens and etiologies. While contact lens associated MK is most
      often associated with bacterial infections, other pathogens (fungi, Acanthamoeba
      species, etc) may be responsible. This review summarizes the risk factors,
      microbiology, diagnostic characteristics, and treatment options for all forms of
      contact lens-related MK.

PMID- 30214347
TI  - Visual performance with multifocal soft contact lenses in non-presbyopic myopic
      eyes during an adaptation period.
AB  - Purpose: Multifocal soft contact lenses (MFCLs) have been proposed and used for
      controlling the rate of myopia progression; however, little is known on the
      performance and adaptation with MFCLs in non-presbyopes. This study aims to
      evaluate the visual performance of four commercially available MFCLs in non
      presbyopic myopic eyes during an adaptation period. Methods: Fifty-two
      experienced myopic contact lens wearers (67% female; mean age 21.4+/-2.0 years)
      were enrolled in this trial and 40 completed the trial. Twenty-six participants
      (Group 1) wore Lotrafilcon B single vision (SV, control), Omafilcon A MFCL center
      distance (D) and center-near (N) and the other 26 participants (Group 2) wore
      Lotrafilcon B SV, Lotrafilcon B MFCL N, and Balafilcon A MFCL N. Lens order was
      randomized. Participants wore each allocated lens for a minimum of 8 days over
      four scheduled visits (dispensing and three follow-up visits) with a 1-week
      washout period between the lens types. At each visit, high-contrast visual acuity
      (HCVA) (in logarithm of the minimum angle of resolution [logMAR]) and seven
      subjective performance variables (via questionnaire) were obtained. Power
      profiles of each lens type, pupil size, and contact lens centration, with lens
      placed on the eye, were measured. Results: The SV control outperformed the MFCLs
      in all variables (P<0.05). There were no significant differences in HCVA over
      time, with the exception of monocular HCVA with Omafilcon A MFCL N, which at the
      end of the adaptation period had significantly (P<0.05) improved by 0.10 logMAR.
      No differences were found between visits for any subjective variables.
      Subjectively, Lotrafilcon B MFCL N performed best and was the only lens that did
      not decenter significantly compared to the SV control. Conversely, Omafilcon A
      MFCL N was the worst performing and most decentered lens (P<0.05, y=-0.39 mm),
      with the greatest plus area under the power profile. Conclusion: MFCLs with
      greatest power variation across the optic zone, a greater plus area under the
      distance labeled power profile, and/or lenses that were significantly decentered
      resulted in the lowest subjective ratings. Over time, quality of vision with
      MFCLs did not change in non-presbyopic myopic participants, with the exception of
      Omafilcon A MFCL N, which showed some adaptation effects.

PMID- 30214346
TI  - Diagnosis and treatment of anterior uveitis: optometric management.
AB  - Anterior uveitis encompasses inflammation of the iris and/or ciliary body and is
      one of the most common types of ocular inflammation that primary eye care
      practitioners will encounter. Anterior uveitis may be caused by a variety of
      etiologies, including infectious, non-infectious, and masquerade diseases. The
      short-term and long-term treatment of uveitis should include the evaluation of
      location, duration, pathology, and laterality, in addition to presenting signs
      and symptoms of the disease. A complete review of systems, thorough examination,
      and laboratory testing, may assist the practitioner in narrowing the list of
      possible causes for the uveitis. This is imperative as once a list of diagnoses
      has been made, a targeted approach to treatment can be pursued.

PMID- 30214348
TI  - Assessment of corneal astigmatism following frown and straight incision forms in
      sutureless manual small incision cataract surgery.
AB  - To investigate which of two tunnel incision forms (frown versus straight) in
      sutureless manual small incision cataract surgery creates more corneal
      astigmatism. Sixty eyes of 60 patients who had consented to undergo cataract
      surgery and to partake in this study were followed from baseline through >12-week
      postoperative period. Values of preoperative and postoperative corneal
      astigmatism for the 60 eyes, measured with a Bausch and Lomb keratometer, were
      extracted from the patients' cataract surgery records. Residual astigmatism was
      computed as the difference between preoperative and postoperative keratometry
      readings. Visual acuity was assessed during the preoperative period and at each
      postoperative visit with a Snellen chart at 6 m. Fifty eyes of 50 patients were
      successfully followed-up on. Overall, the mean residual astigmatism was 0.75+/
      0.12 diopters. The differences in mean residual astigmatism between the two
      different incision groups were statistically significant (t [48]=6.33, P<0.05);
      frown incision group recorded 1.00+/-0.12 diopters, whereas the straight incision
      group recorded 0.50+/-0.12 diopters. No significant difference was observed
      between male and female groups (t [48]=0.24, P>0.05). Residual corneal
      astigmatism in the frown incision group was significantly higher than in the
      straight incision group. Fisher's exact test did not reveal a significant
      association between incision forms and visual acuity during the entire
      postoperative period (P>0.05).

PMID- 30214349
TI  - Myopia in schoolchildren in a rural community in the State of Mexico, Mexico.
AB  - Purpose: This study sought to determine the prevalence of myopia in
      schoolchildren of a rural population in Mexico. Methods: A cross-sectional study
      was conducted in 317 children between 6 and 12 years old. A complete refractive
      examination was performed, including static retinoscopy without cycloplegic
      agents. All procedures were conducted according to the Declaration of Helsinki.
      Results: In total, 9.7% (95% CI: 13.07-6.52) of the examined children were myopic
      (spherical equivalent <= -0.50 D), 4.4% (95% CI: 6.66-2.14) presented astigmatism
      (cylinder <= -1.50 D), and 5.4% (95% CI: 7.89-2.91) presented hyperopia
      (spherical equivalent >= +0.50 D). Conclusion: Additional research is required to
      assess the prevalence of refractive errors in rural areas in Mexico, to analyze
      the associated risk factors, and to implement appropriate eye care plans for this
      population.

PMID- 30214350
TI  - Association between multifocal soft contact lens decentration and visual
      performance.
AB  - Purpose: The aim of this study was to assess the association between decentration
      of several commercial multifocal soft contact lenses (MFCLs) and various
      objective and subjective visual performance variables in presbyopic and non
      presbyopic participants. Materials and methods: All presbyopic (age >40 years,
      near add >=+1.25 D) and non-presbyopic (age >=18 years, no near add requirements,
      spherical equivalent <=-0.50 D) participants were each fitted bilaterally with
      six and two MFCLs (test lens), respectively, and with one single vision lens
      (control lens). Lens decentration, ie, the x- and y-differences between the
      contact lens and pupil centers, was objectively determined. Third-order
      aberrations were measured and compared. Visual performance (high- and low
      contrast acuities and several subjective variables) was analyzed for any
      associations (Pearson's correlation, r) with MFCL decentration. Results: A total
      of 17 presbyopic (55.1+/-6.9 years) and eight non-presbyopic (31.0+/-3.3 years)
      participants completed the study. All lenses displayed a temporal-inferior
      decentration (x=-0.36+/-0.29 mm, y=-0.28+/-0.28 mm, mean +/- SD). Compared to the
      control, a significant inferior decentration was found for the Proclear(r) MFCL
      Near lens in both groups (ypresbyopic =-0.26 mm, ynon-presbyopic =-0.70 mm) and
      for the Proclear(r) MFCL Distance lens in the non-presbyopic group (ynon
      presbyopic =-0.69 mm). In both groups, lens-induced vertical coma (C(3, -1)) was,
      by at least tenfold, significantly more positive for the Proclear(r) MFCL
      Distance lens and significantly more negative for the Proclear(r) MFCL Near lens.
      In the presbyopic group, the correlation of total MFCL decentration with vision
      variables was weak (r<|0.191|). Conversely, a moderate but significant
      correlation with total MFCL decentration was found in the non-presbyopic group
      for most of the vision variables, indicating a decrease in vision as decentration
      increased. Conclusion: Certain MFCLs decentered more than others; the same lens
      designs also induced significant amounts of third-order aberrations. An
      association between MFCL decentration and seven out of nine vision variables was
      found in the non-presbyopic group, ie, the group where lenses were most
      decentered, which had larger pupils and lower levels of inherent third-order
      aberrations.

PMID- 30214351
TI  - Diagnosis and management of blepharitis: an optometrist's perspective.
AB  - Blepharitis is a condition characterized by inflammation of the eyelid margin and
      is a common cause of discomfort and irritation among people of all ages,
      ethnicity, and sex. In general, blepharitis is not a sight-threatening condition,
      but if left untreated has the potential to cause keratopathy, corneal
      neovascularization and ulceration, and permanent alterations in eyelid
      morphology. Historically, blepharitis has been categorized according to multiple
      structural classifications, including anatomic location, duration, and etiology.
      The substantial overlap of symptoms and signs from the differing structural
      classifications has led to initial misdiagnoses, clinical underreporting, and
      variability in treatment of blepharitis. The multifactorial nature is still not
      fully appreciated but infection and inflammation have been identified as the
      primary contributors. Ongoing clinical research continues the pursuit for a
      treatment panacea; however, long-term management of the underlying causes of
      blepharitis remains the best clinical approach. Here, we will attempt to review
      the existing literature as it pertains to clinical management of blepharitis and
      address a stepwise approach to diagnosis, treatment, and management.

PMID- 30214352
TI  - In vivo slit scanning confocal microscopic observation in a patient with moderate
      and severe keratoconus: a case report.
AB  - A 22-year-old Indian female was referred to Sg Buloh hospital with the diagnosis
      of bilateral keratoconus. On examination, slit lamp biomicroscopy and corneal
      topography revealed stage 3 keratoconus in the right eye and stage 2 keratoconus
      in the left eye. Corneal cell morphology in both eyes was evaluated using
      confocal microscope. In qualitative observation, almost all corneal layers in
      right eye except endothelium were partially or completely obscured by haze.
      Additionally, morphological alterations, such as elongation of keratocyte nuclei
      and cluster of cells, and dark bands in the anterior stroma were observed in
      right eye. In the left eye, the amount of haze was less, allowing better
      visibility of the corneal layers compared with the right eye. The dark bands were
      evident in the posterior stroma. Quantitative analysis showed that anterior and
      posterior stromal keratocyte density and endothelium cell density were relatively
      low in the right eye (834.0, 700.5, and 2,133 cells/mm2, respectively) compared
      with the left eye (934.1, 750.6, and 2,361 cells/mm2, respectively). In this
      case, the right eye, exhibiting stage 3 keratoconus, showed more morphological
      alteration, particularly in the anterior stroma compared with the left eye with
      stage 2 keratoconus. Increased severity of the disease can explain these
      differences in corneal cell morphology.

PMID- 30214353
TI  - Prevalence and degrees of myopia and hyperopia at Gondar University Hospital
      Tertiary Eye Care and Training Center, Northwest Ethiopia.
AB  - Background: Refractive errors are the second and third leading cause of visual
      impairment and blindness in Ethiopia, respectively. The situation is worse where
      accessing spectacles, which are the only management option in developing
      countries, is a major issue. Gondar University Hospital Tertiary Eye Care and
      Training Center is the only referral eye care center, and it lacks published
      evidence on the prevalence and degrees of refractive errors (myopia and
      hyperopia). Objective: The purpose of this study was to determine the prevalence
      and degrees of myopia and hyperopia at Gondar University Tertiary Eye Care and
      Training Center. Materials and methods: Records of 1,921 patients presented to
      refraction service at Gondar University Hospital Tertiary Eye Care and Training
      Center from January 2010 to January 2014 were reviewed. All cases of refractive
      errors (with visual improvement of at least one line) were converted into
      spherical equivalents (SE = sphere + 1/2 cylinder). Myopia was defined as SE <= 
      0.25 D and hyperopia >= +0.25 D. Results: The study comprised of 61.1% males and
      38.9% females; the patients had an average age of 40+/-17 years. The overall
      prevalence of refractive errors (myopia and hyperopia) was 76.3% (95% confidence
      interval: 75%-77%). Myopia was present in 34.5% patients and hyperopia in 38.3%.
      Low-degree hyperopia (86%) and low-degree myopia (49.5%) were the most frequent
      refractive errors. Conclusion: Myopia and hyperopia are major reasons for
      patients to visit Gondar University Hospital Tertiary Eye Care and Training
      Center. Low-degree myopia and hyperopia were the most common refractive errors.
      Stocking appropriate power lenses is needed at this tertiary eye care center in
      order to alleviate this problem in Ethiopia.

PMID- 30214354
TI  - The prevalence and causes of decreased visual acuity - a study based on vision
      screening conducted at Enukweni and Mzuzu Foundation Primary Schools, Malawi.
AB  - Aim: To determine the prevalence and causes of decreased visual acuity (VA) among
      pupils recruited in two primary schools in Mzimba district, northern region of
      Malawi. Materials and methods: The study was based on the vision screening which
      was conducted by optometrists at Enukweni and Mzuzu Foundation Primary Schools.
      The measurements during the screening included unaided distance monocular VA by
      using Low Vision Resource Center and Snellen chart, pinhole VA on any subject
      with VA of less than 6/6, refraction, pupil evaluations, ocular movements, ocular
      health, and shadow test. Results: The prevalence of decreased VA was found to be
      low in school-going population (4%, n=594). Even though Enukweni Primary School
      had few participants than Mzuzu Foundation Primary School, it had high prevalence
      of decreased VA (5.8%, n=275) than Mzuzu Foundation Primary School (1.8%, n=319).
      The principal causes of decreased VA in this study were found to be amblyopia and
      uncorrected refractive errors, with myopia being the main cause than hyperopia.
      Conclusion: Based on the low prevalence of decreased VA due to myopia or
      hyperopia, it should not be concluded that refractive errors are an insignificant
      contributor to visual disability in Malawi. More vision screenings are required
      at a large scale on school-aged population to reflect the real situation on the
      ground. Cost-effective strategies are needed to address this easily treatable
      cause of vision impairment.

PMID- 30214355
TI  - Prevalence and associated factors of myopia among high school students in Gondar
      town, northwest Ethiopia, 2016.
AB  - Introduction: Myopia is an important cause of correctable visual impairment and
      preventable blindness worldwide. Prevalence rates are approximately 20%-35% among
      the older teenage population globally. It has a medical burden of pathologic
      complications such as maculopathy and glaucomatous optic neuropathy. High school
      students experience high-performance and study pressures in the preparation for
      the final national examination. As a result they are exposed to excessive near
      work and indoor activities. They are also ignored for regular screening.
      Objective: To determine the prevalence and associated factors of myopia among
      high school students in Gondar town, Ethiopia. Methods: An institution-based
      cross-sectional study was conducted on 498 high school students with systematic
      random sampling method from April 18 to April 29, 2016, in three full-cycle high
      schools (9th-12th grades). A standardized structured questionnaire, Snellen
      acuity chart, pinhole, retinoscope, trial case lenses, pen torch, and direct
      ophthalmoscope were used to collect data. Results: A total of 495 study
      participants were included, and they had a mean age of 17.48+/-1.59 years. The
      prevalence of myopia was 11.9% (95% confidence interval [CI]: 10.2, 17.9). Family
      history of myopia (adjusted odds ratio [AOR]=8.08 [95% CI: 4.30, 15.16]), school
      being private (AOR=2.88 [95% CI: 1.02, 8.11]), longer time spent for near work
      (AOR=2.89 [95% CI: 1.12, 7.43]), longer time spent partaking in indoor activities
      (AOR=4.32 [95% CI: 1.69, 10.99]), shorter near working distance (AOR=3.06 [95%
      CI: 1.33, 7.06]), lack of outdoor sport activities (AOR=2.27 [95% CI: 1.05,
      4.90]), use of visual display units (AOR=2.81 [95% CI: 1.30, 6.10]), and abnormal
      ocular findings (AOR=6.69 [CI: 3.43, 13.03]) were found to be independently
      associated with myopia. Conclusion: The prevalence of myopia was 11.9%. Family
      history for myopia, school being private, longer time spent partaking in indoor
      activities, shorter working distance, lack of outdoor sport activities, use of
      visual display units, and presence of abnormal ocular findings were positively
      associated with myopia.

PMID- 30214356
TI  - Visual outcome of cataract surgery at Gondar University Hospital Tertiary Eye
      Care and Training Center, North West Ethiopia.
AB  - Background: Globally, cataract is the leading cause of blindness which accounts
      for 51% of 39 million blind people. The visual rehabilitation is made through
      sight-restoring surgery. The patients' postoperative visual satisfaction, vision
      related quality of life, ability to function in daily activities and their
      overall productivity mainly depend on the visual outcome. However, there are
      limited data on the visual outcome and its associated factors in the study area.
      Therefore, this study intended to evaluate the postoperative level of visual
      acuity to provide a baseline information regarding visual outcome and design a
      standardized protocol to maximize it. Methods and materials: A hospital-based
      cross-sectional study was conducted at the Gondar University Hospital Tertiary
      Eye Care and Training Center on 223 patients who underwent cataract surgery,
      selected using simple random technique from April to June 2015. Results: This
      study consisted of 218 patients or eyes that underwent cataract surgery. The
      median age of the participants was 65 years with an interquartile range of 20
      years. Of 218 cataract-operated visually impaired eyes (<6/60), 26.6% of them
      achieved good visual acuity (>=6/18), 28.9% of them had borderline acuity (<6/18
      6/60), and the remaining of 44.5% were remained as poor visual acuity (<6/60). It
      has been observed that the postoperative visual acuity had an association with
      postoperative follow up time duration (P=0.035). Conclusion: In this study, the
      visual outcome of cataract surgery was significantly low as compared to World
      Health Organization's recommendations, and it has been recognized that there is
      significant progression of visual acuity in different consecutive weeks.

PMID- 30214357
TI  - Determinants of high unmet need for presbyopia correction: a community-based
      study in northwest Ethiopia.
AB  - Purpose: Lack of evidence on the magnitude of unmet presbyopia need, and barriers
      to uptake spectacles, limit appropriate planning and implementation of the
      provision of spectacles to address the backlog of uncorrected presbyopia. The
      purpose of this study was to determine the magnitude of unmet presbyopia need and
      the associated factors in Bahir Dar, Ethiopia. Materials and methods: A community
      based cross-sectional study was conducted in 2015 in Bahir Dar. A multistage
      sampling technique was used to sample 729 study participants. Individuals more
      than 35 years of age who were unable to read the N8 line on a near vision chart
      unaided or with existing spectacles at 40 cm were considered as having unmet need
      for presbyopia correction. Distance and near visual acuities were measured by
      optometrists using Snellen illiterate E chart at 6 m and 40 m, respectively. Data
      were entered into Epi Info 2002 and analyzed using Statistical Package for Social
      Sciences version 16.0. Odds ratio (with 95% confidence interval [CI]) was used to
      determine the strength of association. P-values <0.05 were considered
      statistically significant. Results: A total of 729 people were included in the
      study (response rate of 99.5%). The mean age +/- standard deviation of
      participants was 48.9+/-8.8 years. Unmet presbyopic need was 69.2% (95% CI: 65.8%
      72.6%). Age (36-45 years [adjusted odds ratio {AOR} = 3.95; 95% CI: 1.06, 4.80]),
      having no eye checkup in the past 1 year (AOR = 8.36; 95% CI: 5.16, 13.7), lack
      of awareness about place of refraction service (AOR = 4.38; 95% CI: 1.36, 13.7),
      and female gender (AOR = 1.78; 95% CI: 1.68, 2.9) were determinants of unmet
      presbyopia need. Conclusion: The burden of unmet presbyopia need is a high
      priority according to the World Health Organization prioritization for provision
      of presbyopia services. Accessible and affordable provision of spectacles with
      health education and promotion efforts are imperative to address the backlog of
      unmet presbyopia correction need in the study area.

PMID- 30214358
TI  - Orthokeratology: clinical utility and patient perspectives.
AB  - Orthokeratology (ortho-k) is a special rigid contact lens worn at night to
      achieve myopic reduction and control. This review provides an overview on
      prescribing ortho-k, including clinical consideration on patient aspect and lens
      design; its clinical outcomes; and clinical efficacy and safety. Patient
      satisfaction was summarized. In order to achieve long-term healthy ortho-k
      treatment, it requires both patient and practitioners' care and rapport to
      maintain good ocular health and lens conditions.

PMID- 30214360
TI  - SIDRE: Symptomatic Improvement of Dry Eye Study.
AB  - Purpose: The aim of this study was to evaluate the effectiveness of lifitegrast
      5% ophthalmic solution in reducing the symptoms of eye dryness using Ocular
      Surface Disease Index (OSDI) questionnaire. Methods: A single-center study was
      undertaken to evaluate the clinical outcomes. Fourteen subjects (12 female and 2
      male) with symptoms of dry eye and a positive history of recent use of artificial
      tears were included in the study. OSDI questionnaire scores on the severity of
      symptoms, visual functionality, and quality of life related to the condition were
      recorded pre- and post-therapy. Subsequently, score data were analyzed for
      statistical significance. Results: The mean age of the 14 subjects was 44.86
      (standard deviation [SD] +/-3.08) years, with a range of 23-62 years. Mean
      duration of the evaluation was 28.79 days with a range of 25-34 days. Baseline
      OSDI mean score was 49.40 (SD +/-1.28), and post-therapy mean score was 42.26 (SD
      +/-0.99). Data analysis revealed that the scores were statistically significantly
      improved post-lifitegrast therapy in comparison to baseline (p=0.00041).
      Conclusion: Lifitegrast 5% ophthalmic solution may be a beneficial therapeutic
      option in the management of symptoms associated with dry eye disease.

PMID- 30214359
TI  - Contact lens wear and dry eyes: challenges and solutions.
AB  - The number of contact lens wearers worldwide has remained relatively stable over
      the past decade, despite the investment that has gone into contact lens
      technology. This is largely because 10%-50% of wearers dropout of contact lens
      wear within 3 years of commencement; the most common reason cited being contact
      lens discomfort (CLD). Of the symptoms reported, sensation of dry eye is the most
      common. Given the outcome of reduced wearing time, increased chair time, and
      ultimate contact lens discontinuation, the challenge is to identify the warning
      signs of CLD early on. Clinically detectable changes such as conjunctival
      staining, conjunctival indentation, conjunctival epithelial flap formation, lid
      wiper epitheliopathy, Demodex blepharitis, and meibomian gland dysfunction have
      been linked to CLD, highlighting the need to perform regular aftercare visits to
      identify these changes. At a cellular level, conjunctival metaplasia and reduced
      goblet cell density have been linked to CLD, leading to a downstream effect on
      the tear film breakup time of contact lens wearers. These factors suggest a
      strong link between CLD and friction, raising the need to target this as a means
      of minimizing CLD. The purpose of this review is to identify the clinical signs
      that relate to CLD as a means of earlier detection and management in order to
      combat contact lens dropout.

PMID- 30214361
TI  - Distance associated heterophoria measured with polarized Cross test of MKH method
      and its relationship to refractive error and age.
AB  - Purpose: Due to the expansion of modern optotype liquid crystal display with the
      help of positive polarization, measurement of heterophorias (HTFs) by means of
      polarization, and thus partial dissociation of perceptions, has become more and
      more accessible. Our aims were to establish the prevalence of distance associated
      HTF by measuring with polarized Cross test of MKH [measuring and correcting
      methodology after H-J Haase] method and its association with age and refractive
      error in clinical population of wide age range. Methods: A cross-sectional study
      was carried out with 170 clinical subjects aged 15-78 years with an average age
      of 40.7+/-16.62 years. All the participants had best-corrected visual acuity
      better than 20/25, stereopsis <=60 second of arc, no heterotropia, not undergone
      vision therapy, and had no eye disease. The distance associated HTF was measured
      with the Cross test of the MKH methodology. The quantification of associated HTF
      was acquired by means of Risley rotary prism. Results: The occurrence of distance
      associated HTF was found in 71.2% of participants. Of the total, 36.5% of the
      cases had esophoria (EP), 9.4% EP and hyperphoria, 10.6% exophoria (XP), 7.1% XP
      and hyperphoria, 7.6% hyperphoria, and 28.8% orthophoria. The mean distance
      horizontal associated HTF was +0.76+/-2.38 Delta. With EP, the mean value was
      +2.47+/-2.18 Delta, and with XP, -2.1+/-1.72 Delta. There was no correlation
      observed between the amount of distance associated HTF and age. There was no
      effect of the type and amount of a refractive error on the amount of distance
      associated HTF. Conclusion: A high occurrence of distance associated HTF was
      revealed while performing the polarized Cross test of MKH method. The
      relationship between the degree of associated HTF and refractive error and age
      was not proved.

PMID- 30214362
TI  - Prevalence and associated factors of computer vision syndrome among bank workers
      in Gondar City, northwest Ethiopia, 2015.
AB  - Introduction: Use of computers is generally encouraged; this is to keep up with
      the fast-moving world of technology, research and science. Extensive use of
      computers will result in computer vision syndrome (CVS), and the prevalence is
      increased dramatically. The main objective of the study was to assess the
      prevalence and associated factors of CVS among bank workers in Gondar city,
      northwest Ethiopia. Methods: A cross-sectional institution-based study was
      conducted among computer-using bank workers in Gondar city from April to June,
      2015. Data were collected through structured questionnaires and observations with
      checklists, entered with Epi InfoTM 7 and analyzed by Statistical Package for the
      Social Sciences (SPSS) version 20. Descriptive statistics and logistic regression
      were carried out to compute the different rates, proportion and relevant
      associations. Results: Among the total 304 computer-using bank workers, the
      prevalence of CVS was 73% (95% confidence interval [CI]=68.04, 78.02). Blurred
      vision (42.4%), headache (23.0%) and redness (23.0%) were the most experienced
      symptoms. Inappropriate sitting position was 2.3 times (adjusted odds ratio
      [AOR]=2.33; 95% CI=1.27, 4.28) more likely to be associated with CVS when
      compared with appropriate sitting position. Those working on the computer for
      more than 20 minutes without break were nearly 2 times (AOR=1.93; 95% CI=1.11,
      3.35) more likely to have suffered from CVS when compared with those taking break
      within 20 minutes, and those wearing eye glasses were 3 times (AOR=3.19; 95%
      CI=1.07, 9.51) more likely to suffer from CVS when compared with those not
      wearing glasses. Conclusion: About three-fourths of computer-using bank workers
      suffered from CVS with the most experienced symptoms being blurred vision,
      headache and redness of eyes. In appropriate sitting position, working on the
      computer without a break for more than 20 minutes and wearing eye glasses were
      independently associated with CVS.

PMID- 30214363
TI  - Targeting modifiable risk factors in age-related macular degeneration in
      optometric practice in Sweden.
AB  - Purpose: The purpose of this study was to investigate the extent to which
      ophthalmologists and optometrists in Sweden recommend the use of nutritional
      supplements, changes in diet, or smoking cessation to patients who are at risk of
      or with signs of age-related macular degeneration (AMD). In addition, this study
      also examined how these practitioners rate the strength of evidence for
      nutritional supplements in AMD management and which sources of information they
      consult to determine supplement recommendations for the prevention or treatment
      of AMD. Methods: This study implemented a cross-sectional design using data from
      a questionnaire. All Swedish optometrists and ophthalmologists who were
      registered in the membership databases of their respective professional
      organizations were invited to participate. The questionnaire contained 18 forced
      choice questions and one free text question and was organized into the following
      four sections: use of nutritional supplements, dietary advice, smoking and eye
      diseases, and strength of evidence and the sources of information regarding
      nutritional supplement interventions. Results: The response rate was 40.3% for
      optometrists and 5% for ophthalmologists. Optometrists were more likely than
      ophthalmologists to recommend nutritional supplements in AMD and provided
      significantly more advice about diet than did the ophthalmologists for both
      patients at risk for AMD and those with established disease. The ophthalmologists
      were more likely than the optometrists to rely on the findings from the age
      related eye disease studies of AMD regarding treatment with and selection of
      supplements and to recommend smoking cessation. Conclusion: Common evidence-based
      strategies for AMD management among eye care professionals would presumably be
      beneficial for AMD patients. Targeted education and implementation strategies may
      be needed.

PMID- 30214364
TI  - Prevalence and associated factors of presbyopia among school teachers in Gondar
      city, Northwest Ethiopia, 2016.
AB  - Introduction: Presbyopia is an age-related decline in accommodation that
      diminishes the ability of the eye to focus on near objects. This is due to
      reduced elasticity of the crystalline lens as age increases. It causes near
      vision impairment and affects near work, so it has significant effects on quality
      of life, particularly in the life of teachers, whose work depends mostly on
      reading and writing at short distances. Objective: The overall objective of the
      study was to assess the prevalence and associated factors of presbyopia among
      school teachers in Gondar city, Northwest Ethiopia, 2016. Methods: A cross
      sectional study design with multistage simple random sampling technique was used
      to select 668 teachers in Gondar city. The study was conducted in 12 schools from
      April 15 to May 15, 2016. A pretested structured questionnaire and ophthalmic
      instruments for an eye examination were used as data collection tools by trained
      optometrists. Epi Info version 7 was used for data entry, and the data were
      exported to Statistical Package for Social Science version 20 for further
      analysis. Multivariate logistic regression was employed using enter method and
      odds ratio with 95% confidence interval, and p-value of <=0.05 was considered to
      identify statistically significant associated factors of the outcome. Results:
      Prevalence of presbyopia among school teachers was 68.7%. Out of the total
      examined subjects, 317 (50.2%) were females. On multivariate analysis, increased
      age, salary, work experience, cigarette smoking, pregnancy, and refractive error
      were positively and significantly associated with presbyopia. On the other hand,
      use of sunglasses and alcohol consumption were inversely and significantly
      associated with presbyopia. Conclusion and recommendation: The study had
      demonstrated a higher prevalence of presbyopia among school teachers. Further
      investigation is recommended to assess the effect of alcohol consumption on
      presbyopia.

PMID- 30214365
TI  - Intrasession repeatability of refractive and ocular aberrometric measurements
      obtained using a multidiagnostic device in healthy eyes.
AB  - Purpose: To evaluate the intrasession repeatability of refractive and ocular
      aberrometric measurements obtained using a new multidiagnostic device in healthy
      eyes. Patients and methods: A total of 107 eyes of 107 patients, age ranging from
      23 to 65 years, were enrolled in this study. A complete eye examination was
      performed in all eyes, including an ocular examination using the VX120 system.
      Three consecutive measurements were obtained using this device to assess the
      intrasession repeatability of different refractive and ocular aber-rometric
      parameters. The within-subject standard deviation (Sw), intrasubject precision
      (1.96*Sw), and intraclass correlation coefficient (ICC) were calculated. Results:
      Sw and intrasubject precision for refractive data were below 0.12 and 0.20 D,
      respectively, in all cases. The ICC ranged from 0.947 for the J45 power vector
      component to 0.997 for the sphere. Concerning aberrometric measurements Sw and
      intrasubject precision values were below 0.05 um and 0.10 um, respectively.
      Likewise, the ICC ranged from 0.805 for the quadrafoil root mean square to 0.954
      for the primary spherical aberration. Poor correlations were found between most
      of the refractive parameters and their Sw (-0.033<=r<=0.053, p>=0.064). Moderate
      and significant positive correlations were found between the magnitude of the
      aberrometric parameters evaluated and their Sw (r>=0.446, p<0.001). Conclusion:
      The new multidiagnostic device evaluated is able to provide consistent
      measurements of refraction and ocular aberrations in healthy eyes. Future studies
      should confirm if this consistency is also observed in highly aberrated eyes.

PMID- 30214366
TI  - Myopia onset and role of peripheral refraction.
AB  - Background: To determine the peripheral refraction characteristics related to 18
      month changes in refraction in Caucasian (Mediterranean) children. Methods: Non
      cycloplegic peripheral refraction at 10 degrees  intervals over the central +/-30
      degrees  of horizontal visual field over 18 months (baseline, 12 months, and 18
      months of follow-up) was conducted in 50 healthy children who were 8 years old.
      Axial length (AL) was also recorded. Relative peripheral refraction (RPR) was
      calculated and eyes were divided into three study groups: non-myopic eyes, myopic
      eyes, and eyes that develop myopia. Results: Myopic eyes showed hyperopic RPR and
      emetropic and hyperopic eyes showed myopic RPR. Univariate analysis of variance
      did not find any statistically significant effect of peripheral refraction
      (F36=0.13; P=1.00) and RPR (F36=0.79; P=0.80) on myopia onset (eyes that
      developed myopia along the study). All the studied groups showed an increase of
      AL, without statistically significant differences between the studied groups
      (F6=0.09; P=0.99). Conclusion: Hyperopic relative peripheral shift change in eyes
      that develop myopia has been found with differences in RPR between myopic
      (hyperopic RPR) and hyperopic or emmetropic eyes (with myopic RPR). The results
      suggest that RPR cannot predict development or progression of myopia in Caucasian
      (Mediterranean) children and the efficacy in slowing myopia progression obtained
      with treatments that manipulate the peripheral refraction is not just driven with
      RPR.

PMID- 30214367
TI  - Contact lens care tips for patients: an optometrist's perspective.
AB  - Contact lens (CL) wear has been a viable alternative to spectacle wear for
      several decades. The interest and desire to wear CLs have been stable in recent
      years, evidenced by the consistency of new wearers into this category of
      refractive correction. CLs have become one of the most commonly used medical
      devices in the market, with more than 40 million wearers in the US. There are
      many activities in which patients report a preference of CL wear over spectacles
      (athletics for example). Nearly all patients (even presbyopic patients) have the
      option of contact lenses today given the expansion of powers and parameters in
      recent years. Patients eyes are getting dryer as factors of age and the
      environment. CL materials have improved in recent years in an attempt to meet the
      challenges of dryer eyes. Despite the improvements in CLs and their care,
      challenges persist. Patient education, handwashing, compliance with care, and
      wearing schedule are some of the challenges that providers face in the care of CL
      patients even today.

PMID- 30214368
TI  - Infantile nystagmus: an optometrist's perspective.
AB  - Infantile nystagmus (IN), previously known as congenital nystagmus, is an
      involuntary to-and-fro movement of the eyes that persists throughout life. IN is
      one of three types of early-onset nystagmus that begin in infancy, alongside
      fusion maldevelopment nystagmus syndrome and spasmus nutans syndrome.
      Optometrists may also encounter patients with acquired nystagmus. The features of
      IN overlap largely with those of fusion maldevelopment nystagmus syndrome,
      spasmus nutans syndrome, and acquired nystagmus, yet the management for each
      subtype is different. Therefore, the optometrist's role is to accurately discern
      IN from other forms of nystagmus and to manage accordingly. As IN is a lifelong
      condition, its presence not only affects the visual function of the individual
      but also their quality of life, both socially and psychologically. In this
      report, we focus on the approaches that involve optometrists in the investigation
      and management of patients with IN. Management includes the prescription of
      optical treatments, low-vision rehabilitation, and other interventions such as
      encouraging the use of the null zone and referral to support groups. Other
      treatments available via ophthalmologists are also briefly discussed in the
      article.

PMID- 30214369
TI  - Changes in blink rate and ocular symptoms during different reading tasks.
AB  - Background: Reading from tablets is fundamental to modern culture. This study
      measured differences in the blink rate and symptoms of ocular discomfort in
      healthy participants during reading from a tablet and a paper book. Methods:
      Forty healthy, normal males subjects were recruited for this study. Subjects were
      video recorded during reading a text presented on an electronic device (9.7 inch
      tablet) and a hard copy format, for 15 min. Ocular discomfort experienced during
      reading was scored using a visual analog scale. Each participant was examined
      performing one of the two tasks (randomized) on one visit and the other on a
      separate visit (crossover design). All subjects were evaluated before the reading
      tasks and every 5 min during 15 min of reading. Results: The mean +/- standard
      deviation blink rate was 19.74 +/- 9.12/min at baseline. The blink rate decreased
      significantly under both reading conditions (to 11.35 +/- 10.20 and 14.93 +/-
      10.90/min when reading from a book and a tablet, respectively). There was no
      significant difference in the blink rate over 15 min during either type of
      reading. The mean discomfort symptom scores were 148 for the book and 134 for the
      tablet; both were significantly higher than baseline. A gradual increase in
      symptoms was found every 5 min during both types of reading. Conclusion: The
      study confirmed that both the blink rate and ocular discomfort symptoms were
      strongly affected during performance of close visual tasks. Both reading
      conditions affected blinking; this may interfere with tear film dynamics. Such
      effects were reflected in the immediate development of ocular symptoms, which
      increased significantly during both types of reading.

PMID- 30214370
TI  - An economic examination of private insurance claims among adolescents and young
      adults who were enrolled in hospice during the last year of life.
AB  - Purpose: The purpose of this study was to generate baseline data on the health
      characteristics, health care utilization, and health care spending among
      privately insured adolescents and young adults (AYA), who were enrolled in
      hospice care during their last year of life. Methods: A retrospective,
      nonexperimental design was used to collect and analyze longitudinal claims data
      from the Truven Health MarketScanTM database. The sample included AYA (aged 15-24
      years) who utilized hospice during their last year of life. Results: Totally,
      17,408 AYA were included in this analysis. Mean hospice length of stay (LOS) was
      low overall, but there was a statistically significant difference in hospice LOS
      in ages 15-19 years (mean 3.56, SD 15.17 days) compared with those aged 20-24
      years (mean 2.26, SD 8.24; P<0.001 days). More than a third (37%) of the AYAs
      used the emergency department during the last year of life and 83% sought care
      from a primary care visit. However, only 6% of the sample who were hospice
      enrollees used frequent inpatient hospital services. Conclusions: This study
      provides preliminary data for private insurance expenditures and clinical
      utilization for AYA who were enrolled in hospice. This analysis also provides
      initial evidence to suggest extremely short hospice LOS for AYAs prior to the end
      of life and represents an area of future research need.

PMID- 30214371
TI  - A national survey: use of the National Board of Medical Examiners(r) basic
      science subject exams and Customized Assessment Services exams in US medical
      schools.
AB  - Purpose: The National Board of Medical Examiners(r) (NBME(r)) offers basic
      science subject exams and exams developed using the Customized Assessment
      Services (CAS) program. The scope and utilization of these exams by US medical
      schools has not been reported. Therefore, this survey aimed to measure US medical
      school usage of NBME(r) basic science subject exams and exams administered using
      the CAS program. Methods: In May 2016 a survey was sent to 139 US medical schools
      with provisional or full accreditation by the Liaison Committee on Medical
      Education(r). Schools were asked if they administered NBME(r) basic science
      subject exams or exams developed using the NBME(r) CAS program. Follow-up
      questions were asked if the school responded "Yes" to administering the exams.
      Results: Responses were received from 46-48 schools (33%-35% response rate). Of
      the schools responding, 7-13 schools (15%-28%) administer an NBME(r) basic
      science subject exam and 14 schools (30%) administer an exam developed using the
      CAS program. Of the schools that administer an NBME(r) basic science exam, 7-12
      (83%-100%) use the exam for summative assessment for a course and 6-11 (77%-100%)
      use the exam results for curricular revision. Twelve schools (86%) that
      administer an NBME(r) exam developed using the CAS program use the exam for
      summative assessment for a course. Time of administration within the curriculum
      for NBME(r) basic science subject exams varied between 1 month prior to >6 months
      prior to students taking the United States Medical Licensing Examination(r) Step
      1. Conclusion: According to our data, most US medical schools responding to the
      survey do not administer NBME(r) basic science subject exams or exams developed
      using the NBME(r) CAS program. Schools that do administer NBME(r) basic science
      subject exams use the exams for summative assessment for a course and curricular
      revision, while exams administered using the CAS program are used predominately
      for summative assessment for a course.

PMID- 30214372
TI  - Peer tutoring scheme: a medical student's perspective.

PMID- 30214373
TI  - Transgender health and its current omission from medical school curriculum:
      medical students' perspective.

PMID- 30214374
TI  - Medical professionalism: perspectives of medical students and residents at Ayder
      Comprehensive and Specialized Hospital, Mekelle, Ethiopia - a cross-sectional
      study.
AB  - Background: Different forms of unprofessionalism in terms of lack of respect,
      preventable medical errors, inability to work together with colleagues, and
      discrimination while providing service these days can be explained by traditional
      perceptions of who is a good doctor and who is not. Objectives: The aim of this
      study was to determine the perspective of medical students and residents on
      medical professionalism. Methods: This was a cross-sectional study. A validated
      tool has been used to collect data from 276 participants. SPSS version 23 has
      been used to analyze and summarize data. Results: Only 30% of respondents were
      females and the rest were males. The overall mean score of professionalism was
      174.96 out of 220. There was no significant difference between male and female
      respondents. However, students from a different phase of the study were
      significantly different in some of the core elements of professionalism. The role
      model was indicated as one way of learning professionalism. Conclusion and
      implication: The overall level of professionalism was observed to be positive.
      However, medical education should focus on the core elements of medical
      professionalism through the teaching and learning process. Medical teachers
      should also focus on being role models for their students as students consider
      them to be a means for learning the qualities of professionalism. The teaching
      institution could strengthen efforts through locating and recognizing
      professional faculty members who can be effective role models.

PMID- 30214375
TI  - Combinational immune-cell therapy of natural killer cells and sorafenib for
      advanced hepatocellular carcinoma: a review.
AB  - Background: High prevalence of hepatocellular carcinoma (HCC) and typically poor
      prognosis of this disease that lead to late stage diagnosis when potentially
      curative therapies are least effective; therefore, development of an effective
      and systematic treatment is an urgent requirement. Main body: In this review,
      several current treatments for HCC patients and their advantages or disadvantages
      were summarized. Moreover, various recent preclinical and clinical studies about
      the performances of "two efficient agents, sorafenib or natural killer (NK)
      cells", against HCC cells were investigated. In addition, the focus this review
      was on the chemo-immunotherapy approach, correlation between sorafenib and NK
      cells and their effects on the performance of each other for better suppression
      of HCC. Conclusion: It was concluded that combinational therapy with sorafenib
      and NK cells might improve the outcome of applied therapeutic approaches for HCC
      patients. Finally, it was also concluded that interaction between sorafenib and
      NK cells is dose and time dependent, therefore, a careful dose and time
      optimizing is necessary for development of a combinational immune-cell therapy.

PMID- 30214376
TI  - Correction to: Expression of B7-H6 expression in human hepatocellular carcinoma
      and its clinical significance.
AB  - [This corrects the article DOI: 10.1186/s12935-018-0627-7.].

PMID- 30214377
TI  - Membrane expression of thymidine kinase 1 and potential clinical relevance in
      lung, breast, and colorectal malignancies.
AB  - Background: Lung, breast, and colorectal malignancies are the leading cause of
      cancer-related deaths in the world causing over 2.8 million cancer-related deaths
      yearly. Despite efforts to improve prevention methods, early detection, and
      treatments, survival rates for advanced stage lung, breast, and colon cancer
      remain low, indicating a critical need to identify cancer-specific biomarkers for
      early detection and treatment. Thymidine kinase 1 (TK1) is a nucleotide salvage
      pathway enzyme involved in cellular proliferation and considered an important
      tumor proliferation biomarker in the serum. In this study, we further
      characterized TK1's potential as a tumor biomarker and immunotherapeutic target
      and clinical relevance. Methods: We assessed TK1 surface localization by flow
      cytometry and confocal microscopy in lung (NCI-H460, A549), breast (MDA-MB-231,
      MCF7), and colorectal (HT-29, SW620) cancer cell lines. We also isolated cell
      surface proteins from HT-29 cells and performed a western blot confirming the
      presence of TK1 on cell membrane protein fractions. To evaluate TK1's clinical
      relevance, we compared TK1 expression levels in normal and malignant tissue
      through flow cytometry and immunohistochemistry. We also analyzed RNA-Seq data
      from The Cancer Genome Atlas (TCGA) to assess differential expression of the TK1
      gene in lung, breast, and colorectal cancer patients. Results: We found
      significant expression of TK1 on the surface of NCI-H460, A549, MDA-MB-231, MCF7,
      and HT-29 cell lines and a strong association between TK1's localization with the
      membrane through confocal microscopy and Western blot. We found negligible TK1
      surface expression in normal healthy tissue and significantly higher TK1
      expression in malignant tissues. Patient data from TCGA revealed that the TK1
      gene expression is upregulated in cancer patients compared to normal healthy
      patients. Conclusions: Our results show that TK1 localizes on the surface of
      lung, breast, and colorectal cell lines and is upregulated in malignant tissues
      and patients compared to healthy tissues and patients. We conclude that TK1 is a
      potential clinical biomarker for the treatment of lung, breast, and colorectal
      cancer.

PMID- 30214378
TI  - Levetiracetam enhances the temozolomide effect on glioblastoma stem cell
      proliferation and apoptosis.
AB  - Background: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor in
      which cancer cells with stem cell-like features, called cancer stem cells (CSCs),
      were identified. Two CSC populations have been previously identified in GBM, one
      derived from the GBM area called enhanced lesion (GCSCs) and the other one from
      the brain area adjacent to the tumor margin (PCSCs) that greatly differ in their
      growth properties and tumor-initiating ability. To date the most effective
      chemotherapy to treat GBM is represented by alkylating agents such as
      temozolomide (TMZ), whose activity can be regulated by histone deacetylases
      (HDACs) inhibitors through the modulation of O6-methylguanine-DNA
      methyltransferase (MGMT) expression. Levetiracetam (LEV), a relatively new
      antiepileptic drug, modulates HDAC levels ultimately silencing MGMT, thus
      increasing TMZ effectiveness. However, an improvement in the therapeutic efficacy
      of TMZ is needed. Methods: Cell proliferation was investigated by BrdU cell
      proliferation assay and by Western Blot analysis of PCNA expression. Apoptosis
      was evaluated by Western Blot and Immunofluorescence analysis of the cleaved
      Caspase-3 expression. MGMT and HDAC4 expression was analyzed by Western Blotting
      and Immunofluorescence. Statistical analysis was performed using the Student's t
      test and Mann-Whitney test. Results: Here we evaluated the effect of TMZ on the
      proliferation rate of the IDH-wildtype GCSCs and PCSCs derived from six patients,
      in comparison with the effects of other drugs such as etoposide, irinotecan and
      carboplatin. Our results demonstrated that TMZ was less effective compared to the
      other agents; hence, we verified the possibility to increase the effect of TMZ by
      combining it with LEV. Here we show that LEV enhances the effect of TMZ on GCSCs
      proliferation (being less effective on PCSCs) by decreasing MGMT expression,
      promoting HDAC4 nuclear translocation and activating apoptotic pathway.
      Conclusions: Although further studies are needed to determine the exact mechanism
      by which LEV makes GBM stem cells more  sensitive to TMZ, these results suggest
      that the clinical therapeutic efficacy of TMZ in GBM might be enhanced by the
      combined treatment with LEV.

PMID- 30214379
TI  - Establishment and characterization of a cell line HCS1220 from human liver
      metastasis of colon cancer.
AB  - Background: To establish one primary cell line of human liver metastasis of colon
      cancer. Methods: HCS1220 cell line was derived from one liver metastasis of colon
      cancer patient's resected tumor sample. The characterization of the cell line was
      defined by karyotype analysis, short tandem repeat (STR) analysis and mycoplasma
      contamination. Subcutaneous injection 1 * 106 cells to four BALB/c nude mice, the
      viable tumors were developed and diagnosed (H&E staining). The expression of
      biomarkers CK20 and CDX2 for colon cancer were determined by immunocytochemistry
      assay. Results: HCS1220 cell line can grow stably and continuously passage.
      During the grow process, the contact loss in the growth process and superimposed
      growth, which could be defined as proliferation of malignant tumor. Chromosome
      analysis revealed the cells derived from human female. The cells were not
      contaminated by mycoplasma. By immunohistochemistry, the cell line was proven to
      express the biomarkers of colon cancer CK20 and CDX2, while a-fetoprotein, hep-1
      and glypican-3 were stained negative, which demonstrated that the HCS1220 cell
      line originating from the intestinal tissue. Conclusions: HCS1220 cell line has
      the characteristics of primary human liver metastasis of colon cancer. The
      results of STR have genetically showed that cell line is original, which can
      provided cell materials for research in vitro and can also help for establishing
      the mechanism model of liver metastasis of colon cancer and preparing, screening
      and evaluating anti-tumor drugs.

PMID- 30214381
TI  - In vitro suppression of inflammatory cytokine response by methionine sulfoximine.
AB  - Background: The glutamine synthetase inhibitor methionine sulfoximine (MSO),
      shown previously to prevent death caused by an inflammatory liver response in
      mice, was tested on in vitro production of cytokines by mouse peritoneal
      macrophages triggered with lipopolysaccharide (LPS). Results: MSO significantly
      reduced the production of Interleukin 6 (IL-6) and Tumor Necrosis Factor Alpha
      (TNFalpha) at 4 and 6 h after LPS-treatment. This reduction did not result from
      decreased transcription of IL-6 and TNFalpha genes, and therefore appeared to
      result from post-transcriptional inhibition of synthesis of these cytokines. MSO
      treatment did not inhibit total protein synthesis and did not reduce the
      production of a third LPS-triggered cytokine CXCL1, so the effect was not a toxic
      or global downregulation of the LPS response. The anti-inflammatory effects of a
      glutamine synthetase inhibitor were seen even though the medium contained
      abundant (2 mM) glutamine, suggesting that the target for this activity was not
      glutamine synthetase. In agreement with this hypothesis, the L,R isomer of MSO,
      which does not inhibit glutamine synthetase and was previously thought to be
      inert, both significantly reduced IL-6 secretion in isolated macrophages and
      increased survival in a mouse model for inflammatory liver failure. Conclusions:
      Our findings provide evidence for a novel target of MSO. Future attempts to
      identify the additional target would therefore also provide a target for
      therapies to treat diseases involving damaging cytokine responses.

PMID- 30214380
TI  - Urban air pollution and climate change: "The Decalogue: Allergy Safe Tree" for
      allergic and respiratory diseases care.
AB  - Background: According to the World Health Organization, air pollution is closely
      associated with climate change and, in particular, with global warming. In
      addition to melting of ice and snow, rising sea level, and flooding of coastal
      areas, global warming is leading to a tropicalization of temperate marine
      ecosystems. Moreover, the effects of air pollution on airway and lung diseases
      are well documented as reported by the World Allergy Organization. Methods:
      Scientific literature was searched for studies investigating the effect of the
      interaction between air pollution and climate change on allergic and respiratory
      diseases. Results: Since 1990s, a multitude of articles and reviews have been
      published on this topic, with many studies confirming that the warming of our
      planet is caused by the "greenhouse effect" as a result of increased emission of
      "greenhouse" gases. Air pollution is also closely linked to global warming: the
      emission of hydrocarbon combustion products leads to increased concentrations of
      biological allergens such as pollens, generating a mixture of these particles
      called particulate matter (PM). The concept is that global warming is linked to
      the emission of hydrocarbon combustion products, since both carbon dioxide and
      heat increase pollen emission into the atmosphere, and all these particles make
      up PM10. However, the understanding of the mechanisms by which PM affects human
      health is still limited. Therefore, several studies are trying to determine the
      causes of global warming. There is also evidence that increased concentrations of
      air pollutants and pollens can activate inflammatory mediators in the airways.
      Our Task Force has prepared a Decalogue of rules addressing public
      administrators, which aims to limit the amount of allergenic pollen in the air
      without sacrificing public green areas. Conclusions: Several studies underscore
      the significant risks of global warming on human health due to increasing levels
      of air pollution. The impact of climate change on respiratory diseases appears
      well documented. The last decades have seen a rise in the concentrations of
      pollens and pollutants in the air. This rise parallels the increase in the number
      of people presenting with allergic symptoms (e.g., allergic rhinitis,
      conjunctivitis, and asthma), who often require emergency medical care. Our hope
      is that scientists from different disciplines will work together with
      institutions, pharmaceutical companies and lay organizations to limit the adverse
      health effects of air pollution and global warming.

PMID- 30214382
TI  - Contribution of diminished kidney transplant GFR to increased circulating
      chemokine ligand 27 level.
AB  - Background: Inflammatory chemokine ligands (CCLs) play an important role in
      cardiovascular disease and allograft injury. CCLs may independently associate
      with diminished estimated glomerular filtration rate (eGFR) in stable renal
      transplant recipients (RTR). Methods: Plasma levels of 19 CCLs (1, 2, 3, 4, 5, 8,
      11, 13, 15, 17, 21, 24, 26, 27, CXCL5, 8, 10, 12 and 13) were measured in a
      cohort of 101 RTR. The cohort was divided according to CKD-EPI equation into
      three groups; group 1: eGFR >= 60 ml/min, group 2: eGFR 30-59.9 ml/min and group
      3 eGFR <= 29.9 ml/min. ANOVA, Krusklwallis, Mann- Whitney Spearman correlation
      and regression analysis tests were used to determine association between reduced
      eGFR and inflammatory CCLs plasma levels measured by multiplex techniques. 20
      healthy subjects with eGFR above 90 ml/min were included as control. Significance
      was sat at < 0.05. Results: Levels of CCLs 1, 4, 15, 27, CXCL8 and CXCL10 were
      significantly different among the four studied groups. Multivariate regression
      analysis (MVA) between eGFR and all CCLs demonstrated that CCL27 was the only
      ligand to remain significantly associated with diminished eGFR {P = 0.021 and r =
      - 0.35,(P = 0.001)}. In a second MVA between CCL 27 and patient's demographics
      and laboratory variables, diminished eGFR, and elevated PTH, out of the twenty
      one available variables remained significantly associated with elevated
      CCL27levels. Conclusion: Diminished eGFR in stable RTR is associated with
      elevated plasma levels of CCL27. This association may explain, at least in part,
      the independent contribution of reduced eGFR to enhanced inflammation in RTR.

PMID- 30214385
TI  - Placebo Effect.
AB  - Nature and Science ran completely different news line-ups this week. But their
      lead stories agreed on one thing: patients matter. Nature led with a story about
      a group of patients who will share in a patent after giving blood and tissue
      samples to scientists. Science chose to lead with the controversial World Medical
      Association decision to recommend restricting the use of placebos in certain
      clinical trials.

PMID- 30214384
TI  - The Envelope, Please.
AB  - Nobel Prize announcements dominated science news this week. The Nature news
      section led with three Prize-winner stories: medicine, physics, and chemistry.
      Science saved the Nobel details for next week and instead led with an announced
      $58 million non-profit effort to sequence the mouse genome and distribute the
      results free of charge.

PMID- 30214386
TI  - Death to the Coral Reefs and More Money for Everybody Else.
AB  - It was a bad week for the residents of the world's rapidly disappearing coral
      reefs, says Science in its lead story. But it was a good week to be a
      mathematician. NSF director Rita Colwell proposed tripling their research budget,
      reports Nature's lead story.

PMID- 30214387
TI  - Scientists May Approach the Bench.
AB  - NASA science is lightening up and embracing microgravity research on the
      International Space Station, reports Nature in this week's lead article.
      Science's lead story covers a group of litigious tissue donors who are trying to
      recover control of their genes.

PMID- 30214388
TI  - Split Decisions, Split Decisions.
AB  - The lead stories in Nature and Science went in opposite directions this week.
      Science chose outer space, launching into NASA's hotly disputed decision to
      shelve a planned mission to Pluto. Nature plunged into inner space with a story
      about a report to the European Commission advising against granting "premature"
      approval to create human embryos for stem-cell research.

PMID- 30214383
TI  - microRNA Regulation in Estrogen Receptor-Positive Breast Cancer and Endocrine
      Therapy.
AB  - As de novo and acquired resistance to standard first line endocrine therapies is
      a growing clinical challenge for estrogen receptor-positive (ER+) breast cancer
      patients, understanding the mechanisms of resistance is critical to develop novel
      therapeutic strategies to prevent therapeutic resistance and improve patient
      outcomes. The widespread post-transcriptional regulatory role that microRNAs
      (miRNAs) can have on various oncogenic pathways has been well-documented. In
      particular, several miRNAs are reported to suppress ERalpha expression via direct
      binding with the 3' UTR of ESR1 mRNA, which can confer resistance to
      estrogen/ERalpha-targeted therapies. In turn, estrogen/ERalpha activation can
      modulate miRNA expression, which may contribute to ER+ breast carcinogenesis.
      Given the reported oncogenic and tumor suppressor functions of miRNAs in ER+
      breast cancer, the targeted regulation of specific miRNAs is emerging as a
      promising strategy to treat ER+ breast cancer and significantly improve patient
      responsiveness to endocrine therapies. In this review, we highlight the major
      miRNA-ER regulatory mechanisms in context with ER+ breast carcinogenesis, as well
      as the critical miRNAs that contribute to endocrine therapy resistance or
      sensitivity. Collectively, this comprehensive review of the current literature
      sheds light on the clinical applications and challenges associated with miRNA
      regulatory mechanisms and novel miRNA targets that may have translational value
      as potential therapeutics for the treatment of ER+ breast cancer.

PMID- 30214389
TI  - A Qualitative Study on Primary Care Integration into an Asian Immigrant-specific
      Behavioural Health Setting in the United States.
AB  - Introduction: Integrating primary care and behavioural health services improves
      access to services and health outcomes among individuals with serious mental
      illness. Integrated care is particularly promising for racial and ethnic minority
      individuals given higher rates of chronic illnesses and poorer access to and
      quality of care compared to Whites. However, little is known about integrated
      care implementation in non-White populations. The aim of this study is to
      identify facilitators and barriers to successful implementation of primary care
      behavioural health integration in a multilingual behavioural healthcare setting.
      Methods: Seven focus groups and five semi-structured interviews were conducted
      with 41 patients and 5 providers participating in integrated care in a community
      mental health clinic in California serving Asian immigrants. Results: Themes
      generated from constant comparative analysis suggest limited system-level
      preconditions and cross-organisational dynamics challenged integrated care. At
      the same time, changing organisational culture and practice, improving patient
      provider and provider-provider communication, and increasing patient involvement
      enhanced clinical outcomes and facilitated successful implementation. Discussion
      and conclusions: Findings highlight the importance of patient involvement, peer
      services and interdisciplinary communication to successfully implement integrated
      care in the face of linguistic and operational challenges in settings serving
      multilingual and multicultural patients.

PMID- 30214390
TI  - Advancing a Systemic Perspective on Multidisciplinary Teams: A Comparative Case
      Study of Work Organisation in Four Multiple Sclerosis Hospitals.
AB  - Introduction: Many care organisations claim to employ multidisciplinary teams,
      but the term is used to describe quite different forms of collaboration. A
      systemic view of the work organisation of care delivery is presented and applied
      in this article that allows to identify and understand often overlooked yet
      important differences regarding team composition, working relationships and
      therapeutic relationships. Theory and Methods: We used modern socio-technical
      systems theory to study care delivery for a particular patient population as a
      system of interrelated activities. The concept of work organisation refers to the
      way in which the composite task of care delivery is divided into distinct tasks
      and how these are grouped in either monodisciplinary or multidisciplinary
      organisational units. The systemic perspective was applied in a comparative case
      study of four Multiple Sclerosis hospitals. Results: Among the hospitals, one was
      characterised by a functional work organisation, with similar tasks grouped in
      monodisciplinary teams. Cross-disciplinary working and therapeutic relationships
      were established on an ad hoc basis. The three other hospitals adopted a more
      process-oriented work organisation (which groups all tasks related to a specific
      care process within a single, multidisciplinary team). The more process-oriented
      the work organisation, the more working relationships and therapeutic
      relationships appeared to be fixed and continuous. Conclusion and discussion: The
      systemic view adopted in this study yields a better understanding of
      multidisciplinary teams through the concept of work organisation. The actual
      composition of multidisciplinary teams, and the related working and therapeutic
      relationships will vary depending on the type of underlying work organisation.
      Further validation of this conclusion will be needed in other settings.

PMID- 30214391
TI  - Model-Based Vestibular Afferent Stimulation: Evaluating Selective Electrode
      Locations and Stimulation Waveform Shapes.
AB  - A dysfunctional vestibular system can be a severe detriment to the quality of
      life of a patient. Recent studies have shown the feasibility for a vestibular
      implant to restore rotational sensation via electrical stimulation of vestibular
      ampullary nerves. However, the optimal stimulation site for selective elicitation
      of the desired nerve is still unknown. We realized a finite element model on the
      basis of MUCT scans of a human inner ear and incorporated naturally distributed,
      artificial neural trajectories. A well-validated neuron model of myelinated
      fibers was incorporated to predict nerve responses to electrical stimulation.
      Several virtual electrodes were placed in locations of interest inside the bony
      labyrinth (intra-labyrinthine) and inside the temporal bone, near the target
      nerves (extra-labyrinthine), to determine preferred stimulation sites and
      electrode insertion depths. We investigated various monopolar and bipolar
      electrode configurations as well as different pulse waveform shapes for their
      ability to selectively stimulate the target nerve and for their energy
      consumption. The selectivity was evaluated with an objective measure of the fiber
      recruitment. Considerable differences of required energy and achievable
      selectivity between the configurations were observed. Bipolar, intra-labyrinthine
      electrodes provided the best selectivities but also consumed the highest amount
      of energy. Bipolar, extra-labyrinthine configurations did not offer any
      advantages compared to the monopolar approach. No selective stimulation could be
      performed with the monopolar, intra-labyrinthine approach. The monopolar, extra
      labyrinthine electrodes required the least energy for satisfactory selectivities,
      making it the most promising approach for functional vestibular implants.
      Different pulse waveform shapes did not affect the achieved selectivity
      considerably but shorter pulse durations showed consistently a more selective
      activation of the target nerves. A cathodic, centered triangular waveform shape
      was identified as the most energy-efficient of the tested shapes. Based on these
      simulations we are able to recommend the monopolar, extra-labyrinthine
      stimulation approach with cathodic, centered triangular pulses as good trade-off
      between selectivity and energy consumption. Future implant designs could benefit
      from the findings presented here.

PMID- 30214394
TI  - Dopamine Modulates Homeostatic Excitatory Synaptic Plasticity of Immature Dentate
      Granule Cells in Entorhino-Hippocampal Slice Cultures.
AB  - Homeostatic plasticity mechanisms maintain neurons in a stable state. To what
      extent these mechanisms are relevant during the structural and functional
      maturation of neural tissue is poorly understood. To reveal developmental changes
      of a major homeostatic plasticity mechanism, i.e., homeostatic excitatory
      synaptic plasticity, we analyzed 1-week- and 4-week-old entorhino-hippocampal
      slice cultures and investigated the ability of immature and mature dentate
      granule cells (GCs) to express this form of plasticity. Our experiments
      demonstrate that immature GCs are capable of adjusting their excitatory synaptic
      strength in a compensatory manner at early postnatal stages, i.e., in 1-week-old
      preparations, as is the case for mature GCs. This ability of immature dentate GCs
      is absent in 4-week-old slice cultures. Further investigations into the signaling
      pathways reveal an important role of dopamine (DA), which prevents homeostatic
      synaptic up-scaling of immature GCs in young cultures, whereas it does not affect
      immature and mature GCs in 4-week-old preparations. Together, these results
      disclose the ability of immature GCs to express homeostatic synaptic plasticity
      during early postnatal development. They hint toward a novel role of dopaminergic
      signaling, which may gate activity-dependent changes of newly born neurons by
      blocking homeostasis.

PMID- 30214392
TI  - Parkinson's Disease: Biomarkers, Treatment, and Risk Factors.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder caused
      mainly by lack of dopamine in the brain. Dopamine is a neurotransmitter involved
      in movement, motivation, memory, and other functions; its level is decreased in
      PD brain as a result of dopaminergic cell death. Dopamine loss in PD brain is a
      cause of motor deficiency and, possibly, a reason of the cognitive deficit
      observed in some PD patients. PD is mostly not recognized in its early stage
      because of a long latency between the first damage to dopaminergic cells and the
      onset of clinical symptoms. Therefore, it is very important to find reliable
      molecular biomarkers that can distinguish PD from other conditions, monitor its
      progression, or give an indication of a positive response to a therapeutic
      intervention. PD biomarkers can be subdivided into four main types: clinical,
      imaging, biochemical, and genetic. For a long time protein biomarkers, dopamine
      metabolites, amino acids, etc. in blood, serum, cerebrospinal liquid (CSF) were
      considered the most promising. Among the candidate biomarkers that have been
      tested, various forms of alpha-synuclein (alpha-syn), i.e., soluble, aggregated,
      post-translationally modified, etc. were considered potentially the most
      efficient. However, the encouraging recent results suggest that microRNA-based
      analysis may bring considerable progress, especially if it is combined with alpha
      syn data. Another promising analysis is the advanced metabolite profiling of body
      fluids, called "metabolomics" which may uncover metabolic fingerprints specific
      for various stages of PD. Conventional pharmacological treatment of PD is based
      on the replacement of dopamine using dopamine precursors (levodopa, L-DOPA, L-3,4
      dihydroxyphenylalanine), dopamine agonists (amantadine, apomorphine) and MAO-B
      inhibitors (selegiline, rasagiline), which can be used alone or in combination
      with each other. Potential risk factors include environmental toxins, drugs,
      pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects.
      This review covers molecules that might act as the biomarkers of PD. Then, PD
      risk factors (including genetics and non-genetic factors) and PD treatment
      options are discussed.

PMID- 30214393
TI  - cAMP Response Element-Binding Protein (CREB): A Possible Signaling Molecule Link
      in the Pathophysiology of Schizophrenia.
AB  - Dopamine is a brain neurotransmitter involved in the pathology of schizophrenia.
      The dopamine hypothesis states that, in schizophrenia, dopaminergic signal
      transduction is hyperactive. The cAMP-response element binding protein (CREB) is
      an intracellular protein that regulates the expression of genes that are
      important in dopaminergic neurons. Dopamine affects the phosphorylation of CREB
      via G protein-coupled receptors. Neurotrophins, such as brain derived growth
      factor (BDNF), are critical regulators during neurodevelopment and synaptic
      plasticity. The CREB is one of the major regulators of neurotrophin responses
      since phosphorylated CREB binds to a specific sequence in the promoter of BDNF
      and regulates its transcription. Moreover, susceptibility genes associated with
      schizophrenia also target and stimulate the activity of CREB. Abnormalities of
      CREB expression is observed in the brain of individuals suffering from
      schizophrenia, and two variants (-933T to C and -413G to A) were found only in
      schizophrenic patients. The CREB was also involved in the therapy of animal
      models of schizophrenia. Collectively, these findings suggest a link between CREB
      and the pathophysiology of schizophrenia. This review provides an overview of
      CREB structure, expression, and biological functions in the brain and its
      interaction with dopamine signaling, neurotrophins, and susceptibility genes for
      schizophrenia. Animal models in which CREB function is modulated, by either
      overexpression of the protein or knocked down through gene deletion/mutation,
      implicating CREB in schizophrenia and antipsychotic drugs efficacy are also
      discussed. Targeting research and drug development on CREB could potentially
      accelerate the development of novel medications against schizophrenia.

PMID- 30214395
TI  - Deciphering the Contributions of CRH Receptors in the Brain and Pituitary to
      Stress-Induced Inhibition of the Reproductive Axis.
AB  - Based on pharmacological studies, corticotropin-releasing hormone (CRH) and its
      receptors play a leading role in the inhibition of the hypothalamic-pituitary
      gonadal (HPG) axis during acute stress. To further study the effects of CRH
      receptor signaling on the HPG axis, we generated and/or employed male mice
      lacking CRH receptor type 1 (CRHR1) or type 2 (CRHR2) in gonadotropin-releasing
      hormone neurons, GABAergic neurons, or in all central neurons and glia. The
      deletion of CRHRs revealed a preserved decrease of plasma luteinizing hormone
      (LH) in response to either psychophysical or immunological stress. However, under
      basal conditions, central infusion of CRH into mice lacking CRHR1 in all central
      neurons and glia, or application of CRH to pituitary cultures from mice lacking
      CRHR2, failed to suppress LH release, unlike in controls. Our results, taken
      together with those of the earlier pharmacological studies, suggest that
      inhibition of the male HPG axis during acute stress is mediated by other factors
      along with CRH, and that CRH suppresses the HPG axis at the central and pituitary
      levels via CRHR1 and CRHR2, respectively.

PMID- 30214398
TI  - Microglial Implication in Parkinson's Disease: Loss of Beneficial Physiological
      Roles or Gain of Inflammatory Functions?
AB  - Microglia, often described as the brain-resident macrophages, play crucial roles
      in central nervous system development, maintenance, plasticity, and adaptation to
      the environment. Both aging and chronic stress promote microglial morphological
      and functional changes, which can lead to the development of brain pathologies
      including Parkinson's disease (PD). Indeed, aging, and chronic stress represent
      main environmental risk factors for PD. In these conditions, microglia are known
      to undergo different morphological and functional changes. Inflammation is an
      important component of PD and disequilibrium between pro- and anti-inflammatory
      microglial functions might constitute a crucial component of PD onset and
      progression. Cumulated data also suggest that, during PD, microglia might lose
      beneficial functions and gain detrimental ones, in addition to mediating
      inflammation. In this mini-review, we aim to summarize the literature discussing
      the functional and morphological changes that microglia undergo in PD
      pathophysiology and upon exposure to its two main environmental risk factors,
      aging, and chronic stress.

PMID- 30214399
TI  - Positive Connectivity Predicts the Dynamic Intrinsic Topology of the Human Brain
      Network.
AB  - Functional connectivity MRI (fcMRI) has become instrumental in facilitating
      research of human brain network organization in terms of coincident interactions
      between positive and negative synchronizations of large-scale neuronal systems.
      Although there is a common agreement concerning the interpretation of positive
      couplings between brain areas, a major debate has been made in disentangling the
      nature of negative connectivity patterns in terms of its emergence in several
      methodological approaches and its significance/meaning in specific
      neuropsychiatric diseases. It is still not clear what information the functional
      negative correlations or connectivity provides or how they relate to the positive
      connectivity. Through implementing stepwise functional connectivity (SFC)
      analysis and studying the causality of functional topological patterns, this
      study aims to shed light on the relationship between positive and negative
      connectivity in the human brain functional connectome. We found that the strength
      of negative correlations between voxel-pairs relates to their positive
      connectivity path-length. More importantly, our study describes how the spatio
      temporal patterns of positive connectivity explain the evolving changes of
      negative connectivity over time, but not the other way around. This finding
      suggests that positive and negative connectivity do not display equivalent forces
      but shows that the positive connectivity has a dominant role in the overall human
      brain functional connectome. This phenomenon provides novel insights about the
      nature of positive and negative correlations in fcMRI and will potentially help
      new developments for neuroimaging biomarkers.

PMID- 30214397
TI  - Ketogenic Diet Modulates NAD+-Dependent Enzymes and Reduces DNA Damage in
      Hippocampus.
AB  - The ketogenic diet's (KD) anti-seizure effects have long been documented.
      Recently, its therapeutic potential in multiple neurodegenerative and
      neurodevelopmental disorders has emerged. Yet experimental evidence for a
      fundamental mechanism underlying beneficial effects across numerous diseases
      remains lacking. We previously showed that feeding rats a KD produced an early
      (within 2 days) and persistent elevation of hippocampal nicotinamide adenine
      dinucleotide+ (NAD+), an essential metabolic coenzyme and signaling molecule.
      NAD+ is a marker of cellular health and a substrate for enzymes implicated in
      longevity and DNA damage repair such as sirtuins and poly-ADP ribose polymerase-1
      (PARP-1). As a result, activation of NAD+-dependent enzymes' downstream pathways
      could be the origin of KD's broad beneficial effects. Here rats were fed ad
      libitum regular chow or KD for 2 days or 3 weeks and the levels of hippocampal
      sirtuins, PARP-1, and the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine
      were quantified. We found a significant immediate and persistent increase in the
      collective activity of nuclear sirtuin enzymes, and a significant augmentation of
      Sirt1 mRNA at 2 days. Levels of PARP-1 and 8-hydroxy-2'-deoxyguanosine decreased
      after 2 days of treatment and further declined at 3 weeks. Our data show that a
      KD can rapidly modulate energy metabolism by acting on NAD+-dependent enzymes and
      their downstream pathways. Thus, therapy with a KD can potentially enhance brain
      health and increase overall healthspan via NAD+-related mechanisms that render
      cells more resilient against DNA damage and a host of metabolic, epileptic,
      neurodegenerative, or neurodevelopmental insults.

PMID- 30214400
TI  - Moral Violations and the Experience of Disgust and Anger.
AB  - Disgust is a natural defensive emotion that has evolved to protect against
      potential sources of contamination and has been recently linked to moral
      judgements in many studies. However, that people often report feelings of disgust
      when thinking about feces or moral transgressions alike does not necessarily mean
      that the same mechanisms mediate these reactions. The present study used
      functional magnetic resonance imaging (n = 22) to investigate whether core and
      moral disgusts entrain common neural systems. We provide evidence that: (i)
      activation of overlapping brain regions between core and moral disgust is the
      result of content overlap in the vignettes-core disgust elicitors-across
      conditions, and not from moral violations per se, and (ii) moral residue (i.e.,
      the remaining or "residual" activation after the influence of core disgust
      elicitors have been taken into account) produced a pattern of activation that is
      more consistent with moral anger, than one of "residual disgust." These findings
      run contrary to the premise that our "moral center" is connected to the area of
      the brain in which physical revulsion is located.

PMID- 30214396
TI  - The Two Main Olfactory Receptor Families in Drosophila, ORs and IRs: A
      Comparative Approach.
AB  - Most insect species rely on the detection of olfactory cues for critical
      behaviors for the survival of the species, e.g., finding food, suitable mates and
      appropriate egg-laying sites. Although insects show a diverse array of molecular
      receptors dedicated to the detection of sensory cues, two main types of molecular
      receptors have been described as responsible for olfactory reception in
      Drosophila, the odorant receptors (ORs) and the ionotropic receptors (IRs).
      Although both receptor families share the role of being the first chemosensors in
      the insect olfactory system, they show distinct evolutionary origins and several
      distinct structural and functional characteristics. While ORs are seven
      transmembrane-domain receptor proteins, IRs are related to the ionotropic
      glutamate receptor (iGluR) family. Both types of receptors are expressed on the
      olfactory sensory neurons (OSNs) of the main olfactory organ, the antenna, but
      they are housed in different types of sensilla, IRs in coeloconic sensilla and
      ORs in basiconic and trichoid sensilla. More importantly, from the functional
      point of view, they display different odorant specificity profiles. Research
      advances in the last decade have improved our understanding of the molecular
      basis, evolution and functional roles of these two families, but there are still
      controversies and unsolved key questions that remain to be answered. Here, we
      present an updated review on the advances of the genetic basis, evolution,
      structure, functional response and regulation of both types of chemosensory
      receptors. We use a comparative approach to highlight the similarities and
      differences among them. Moreover, we will discuss major open questions in the
      field of olfactory reception in insects. A comprehensive analysis of the
      structural and functional convergence and divergence of both types of receptors
      will help in elucidating the molecular basis of the function and regulation of
      chemoreception in insects.

PMID- 30214401
TI  - Exhaustive Multi-Parametric Assessment of the Behavioral Array of Daily
      Activities of Mice Using Cluster and Factor Analysis.
AB  - Using automated supervised behavioral assessment software, we recorded and
      analyzed 24 h non-interrupted recordings of mice for a duration of 11 days. With
      the assistance of free R programming, we used correlation matrix-based
      hierarchical clustering and factor analysis to separate the 33 activities into
      meaningful clusters and groups without losing the exhaustive nature of the
      findings. These groups represent novel meaningful behavioral patterns exhibited
      by mice in home cage. Thirty-three activities were separated into 5 clusters
      based on dissimilarity between activities and 6 factors based on statistical
      modeling. Using these two methods, we describe and compare behavioral arrays of
      two groups of animals: 1. Continuously recorded for 11 days in social isolation
      and 2. Intermittently socially isolated for recording on days 1, 3, 5, 8, and 10,
      while socializing on the other days. This is the first work to our knowledge that
      interprets mouse home cage activities throughout a 24 h period and proposes a
      base line of a daily routine of a healthy C57Bl/6J mouse that can be used for
      various experimental paradigms, including disease, neuroinflammation, or drug
      testing to trace behavioral changes that follow intervention. In this work, we
      defined the necessary acclimatization period for the 24 h recording paradigm of
      home cage behavior. We demonstrated the behavioral changes that are associated
      with the effect of social isolation, intermittent socialization, and re
      introduction to a familiar home cage. We provide the full description of the
      codes used in R.

PMID- 30214404
TI  - Expanding the Active Inference Landscape: More Intrinsic Motivations in the
      Perception-Action Loop.
AB  - Active inference is an ambitious theory that treats perception, inference, and
      action selection of autonomous agents under the heading of a single principle. It
      suggests biologically plausible explanations for many cognitive phenomena,
      including consciousness. In active inference, action selection is driven by an
      objective function that evaluates possible future actions with respect to
      current, inferred beliefs about the world. Active inference at its core is
      independent from extrinsic rewards, resulting in a high level of robustness
      across e.g., different environments or agent morphologies. In the literature,
      paradigms that share this independence have been summarized under the notion of
      intrinsic motivations. In general and in contrast to active inference, these
      models of motivation come without a commitment to particular inference and action
      selection mechanisms. In this article, we study if the inference and action
      selection machinery of active inference can also be used by alternatives to the
      originally included intrinsic motivation. The perception-action loop explicitly
      relates inference and action selection to the environment and agent memory, and
      is consequently used as foundation for our analysis. We reconstruct the active
      inference approach, locate the original formulation within, and show how
      alternative intrinsic motivations can be used while keeping many of the original
      features intact. Furthermore, we illustrate the connection to universal
      reinforcement learning by means of our formalism. Active inference research may
      profit from comparisons of the dynamics induced by alternative intrinsic
      motivations. Research on intrinsic motivations may profit from an additional way
      to implement intrinsically motivated agents that also share the biological
      plausibility of active inference.

PMID- 30214402
TI  - Asthma Induction During Development and Adult Lung Function, Behavior and Brain
      Gene Expression.
AB  - In developing youth, allergic asthma is the most common chronic condition, with
      9%-10% of youth affected. Asthma onset during childhood and adolescence is
      further associated with other health issues, particularly psychiatric conditions.
      To understand causal mechanisms by which developmental asthma may lead to altered
      behavior, brain and health trajectories, we developed a mouse model of
      developmental allergic asthma. In the current study, we tested for potential long
      term effects of developmental asthma on adult lung function and behavior and
      brain gene expression associated with emotion and stress regulation. We
      manipulated airway inflammation (AI) and methacholine (MCH)-induced bronchospasm
      (resulting in labored breathing, LB) in young male and female BALB/cJ mice and
      measured adult outcomes 3 months after final asthma manipulations. Results
      indicated that allergen exposure, used to cause AI, and which ended on post-natal
      day 56 (P56), led to persistent lung AI, mucus buildup and gene expression
      related to allergic asthma 3 months after final allergen exposure. In addition,
      at this same age, early allergen exposure led to altered brain gene expression
      related to stress regulation (prefrontal corticotropin releasing hormone receptor
      1, Crhr1 and hippocampal glucocorticoid receptor, GR) and serotonin function
      (brainstem serotonin transporter, SERT). On the other hand, LB events during
      development led to altered anxiety-related behavior. Importantly, sex and pre
      asthma fear-related behavior (ultrasonic vocalization, USV rates) modulated these
      adult outcomes. Asthma that develops during childhood/adolescence may have long
      term impacts on emotion and stress regulation mechanisms, and these influences
      may be moderated by sex and pre-asthma temperament.

PMID- 30214405
TI  - Editorial: Neural Computation in Embodied Closed-Loop Systems for the Generation
      of Complex Behavior: From Biology to Technology.

PMID- 30214403
TI  - EEG Resting State Functional Connectivity in Adult Dyslexics Using Phase Lag
      Index and Graph Analysis.
AB  - Developmental dyslexia may involve deficits in functional connectivity across
      widespread brain networks that enable fluent reading. We investigated the large
      scale organization of electroencephalography (EEG) functional networks at rest in
      28 dyslexics and 36 typically reading adults. For each frequency band (delta,
      theta alpha and beta), we assessed functional connectivity strength with the
      phase lag index (PLI). Network topology was examined using minimum spanning tree
      (MST) graphs derived from the functional connectivity matrices. We found
      significant group differences in the alpha band (8-13 Hz). The graph analysis
      indicated more interconnected nodes, in dyslexics compared to typical readers.
      The graph metrics were significantly correlated with age in dyslexics but not in
      typical readers, which may indicate more heterogeneity in maturation of brain
      networks in dyslexics. The present findings support the involvement of alpha
      oscillations in higher cognition and the sensitivity of graph metrics to
      characterize functional networks in adult dyslexia. Finally, the current results
      extend our previous findings on children.

PMID- 30214406
TI  - Physical Activity, Nutrition, Cognition, Neurophysiology, and Short-Time Synaptic
      Plasticity in Healthy Older Adults: A Cross-Sectional Study.
AB  - The aging brain undergoes remodeling processes because of biological and
      environmental factors. To counteract brain aging, neuronal plasticity should be
      preserved. The aim of this study was to test if the capacity of generating short
      time synaptic plasticity in older adults may be related to either physical
      activity, nutritional status, cognition, or neurophysiological activity. Thirty
      six participants (mean age 73.3 +/- 5.9 years) received transcranial magnetic
      stimulation in combination with peripheral nerve stimulation to experimentally
      induce short-time synaptic plasticity by paired associative stimulation (PAS).
      Adaptations in neuronal excitability were assessed by motor-evoked potential
      (MEP) in the right m. tibialis anterior before and after PAS. The Physical
      Activity Questionnaire 50+ and the StepWatchTM captured physical activity levels.
      Nutritional status was assessed by the Mini Nutritional Assessment. Cognition was
      assessed by reaction time for a divided attention test and with the Montreal
      Cognitive Assessment. Neurophysiological activity was assessed by
      electroencephalography during the divided attention test. MEPs of the highest
      stimulation intensity resulted significantly different comparing before, 5 min,
      or 30 min after PAS (p < 0.05). Data-driven automatic hierarchical classification
      of the individual recruitment curve slopes over the three-time points indicated
      four different response types, however, response groups did not significantly
      differ based on physical activity, nutritional status, cognition, or
      neurophysiological activity. In a second-level analysis, participants having an
      increased slope showed a significant higher energy expenditure (z = -2.165, p =
      0.030, r = 0.36) and revealed a significant higher power activity in the alpha
      frequency band (z = -2.008, p = 0.046, r = 0.37) at the prefrontal-located EEG
      electrodes, compared to the participants having a decreased slope. This study
      hints toward older adults differing in their neuronal excitability which is
      strongly associated to their short-time synaptic plasticity levels. Furthermore,
      a physically active lifestyle and higher EEG power in the alpha frequency band
      seem to be connected to the capacity of generating long-term potentiation-like
      synaptic plasticity in older adults. Future studies should consider more
      sensitive assessments and bigger sample sizes to get a broad scope of the older
      adults' population.

PMID- 30214408
TI  - Measuring Health-Related Quality of Life in Tuberous Sclerosis Complex -
      Psychometric Evaluation of Three Instruments in Individuals With Refractory
      Epilepsy.
AB  - Tuberous sclerosis complex (TSC) is a rare genetic disease associated with
      significant disease burden and considerable impact on health-related quality of
      life (HRQL). Currently no disease-specific clinical outcome assessments evaluate
      HRQL in individuals with TSC. A multi-center phase III study EXIST-3
      (NCT01713946) assessed the efficacy and safety of two trough exposure ranges (Low
      exposure, LE: 3-7 ng/mL and high exposure, HE: 9-15 ng/mL) of adjunctive
      everolimus in patients aged 2-65 years with TSC and refractory partial-onset
      seizures (N = 366). Three age-specific HRQL measures were included as secondary
      endpoints including: quality of life in childhood epilepsy (QOLCE; caregiver
      report for aged 2- < 11), the Quality of Life in Epilepsy Inventory for
      Adolescents-48 (QOLIE-AD-48; self-report, aged >= 11- < 18), and the Quality of
      Life in Epilepsy Inventory-31-Problems (QOLIE-31-P; self-report, aged >= 18).
      Intellectual ability was evaluated using the Wechsler Non-Verbal (WNV) Scale of
      Ability. Post hoc analyses were performed on the core phase primary data from
      EXIST-3 to evaluate the psychometric properties of the HRQL measures and
      calculate meaningful change estimates. Results showed that a significant subset
      of the trial sample (4-21 year olds) scored in the intellectual disability range,
      as assessed by the WNV. Psychometric analyses of the three epilepsy measures
      (including reliability, validity, and ability to detect change) supported the
      appropriateness for use in TSC. Distribution-based meaningful change estimates
      were generated for each HRQL measure, with estimates for the QOLIE-31-P total
      score largely consistent with the published literature. To our knowledge, this is
      the first evaluation using clinical trial data to establish the psychometric
      properties of the QOLCE, QOLIE-AD-48, and QOLIE-31-P for use in individuals with
      TSC. These findings increase confidence in the measures as valid and reliable for
      use in clinical trials and future research in patients with TSC.

PMID- 30214407
TI  - Mapping the Interface of a GPCR Dimer: A Structural Model of the A2A Adenosine
      and D2 Dopamine Receptor Heteromer.
AB  - The A2A adenosine (A2AR) and D2 dopamine (D2R) receptors form oligomers in the
      cell membrane and allosteric interactions across the A2AR-D2R heteromer represent
      a target for development of drugs against central nervous system disorders.
      However, understanding of the molecular determinants of A2AR-D2R heteromerization
      and the allosteric antagonistic interactions between the receptor protomers is
      still limited. In this work, a structural model of the A2AR-D2R heterodimer was
      generated using a combined experimental and computational approach. Regions
      involved in the heteromer interface were modeled based on the effects of peptides
      derived from the transmembrane (TM) helices on A2AR-D2R receptor-receptor
      interactions in bioluminescence resonance energy transfer (BRET) and proximity
      ligation assays. Peptides corresponding to TM-IV and TM-V of the A2AR blocked
      heterodimer interactions and disrupted the allosteric effect of A2AR activation
      on D2R agonist binding. Protein-protein docking was used to construct a model of
      the A2AR-D2R heterodimer with a TM-IV/V interface, which was refined using
      molecular dynamics simulations. Mutations in the predicted interface reduced A2AR
      D2R interactions in BRET experiments and altered the allosteric modulation. The
      heterodimer model provided insights into the structural basis of allosteric
      modulation and the technique developed to characterize the A2AR-D2R interface can
      be extended to study the many other G protein-coupled receptors that engage in
      heteroreceptor complexes.

PMID- 30214409
TI  - Chinese Herbal Medicine for Myasthenia Gravis: A Systematic Review and Meta
      Analysis.
AB  - Myasthenia gravis (MG) is an acquired autoimmune disease with the disorder of the
      neuromuscular junction transmission caused by autoantibodies. Currently, various
      Chinese herbal medicines (CHMs) are widely used for MG. This meta-analysis was
      conducted to assess the effectiveness and safety of CHMs for MG and its possible
      mechanisms. Fourteen studies with 1039 individuals were identified by searching
      seven databases from inception to March 2017. The methodological quality was
      assessed by using 7-item criteria from the Cochrane's Collaboration tool, and
      which assessed >=4 "yes" in the domains were selected for detailed assessment and
      meta-analysis. All the data were analyzed using Rev-Man 5.3 software. Meta
      analysis showed a significant effect of CHM as adjuvant therapy for improving the
      effectiveness compared with WCM alone or placebo in treating MG (p < 0.01).
      Moreover, there were fewer adverse effects and relapse rate in total when
      compared with the control group. The possible mechanisms of CHM for MG are
      associated with immunoregulation by reconstituting the functional ability of
      Tregs. In conclusion, despite the apparent positive results, the present evidence
      supports, to an extent, that CHM can be used for MG patients because of the
      methodological flaws and CHM heterogeneity. Further rigorous RCT for MG is
      needed.

PMID- 30214410
TI  - Magnoflorine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via
      Suppressing NF-kappaB and MAPK Activation.
AB  - Acute lung injury (ALI) which is featured by a strong pulmonary inflammation, is
      a major cause of morbidity and mortality in critically ill patients.
      Magnoflorine, a quaternary alkaloid isolated from Chinese herb Magnolia or
      Aristolochia, has been reported to have potent anti-inflammatory properties.
      However, the effect of magnoflorine on lipopolysaccharide (LPS)-induced ALI in
      mice has not been reported. The purpose of the present study is to investigate
      the anti-inflammatory effect of magnoflorine on LPS-induced ALI and elucidate its
      possible molecular mechanisms in RAW264.7 cells. The results of histopathological
      changes as well as the myeloperoxidase (MPO) activity indicated that magnoflorine
      significantly alleviated the lung injury induced by LPS. In addition, qPCR
      results showed that magnoflorine dose-dependently decreased the expression of pro
      inflammatory cytokines TNF-alpha, IL-1beta, and IL-6. Immunofluorescence assay
      also confirmed that the level of Toll-like receptor 4 (TLR4) induced by LPS was
      inhibited by magnoflorine treatment. Further experiments were performed using
      Western blotting to detect the expression of related proteins in the NF-kappaB
      and MAPK signaling pathways. The results showed that magnoflorine suppressed the
      levels of phosphorylated p65, IkappaBalpha, p38, ERK, and JNK. In conclusion, all
      data indicate that magnoflorine could protect against LPS-induced inflammation in
      ALI at least partially by inhibiting TLR4-mediated NF-kappaB and MAPK signaling
      pathways.

PMID- 30214411
TI  - Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy,
      Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats.
AB  - Koumine, an indole alkaloid, is a major bioactive component of Gelsemium elegans.
      Previous studies have demonstrated that koumine has noticeable anti-inflammatory
      and analgesic effects in inflammatory and neuropathic pain (NP) models, but the
      mechanisms involved are not well understood. This study was designed to explore
      the analgesic effect of koumine on chronic constriction injury (CCI)-induced NP
      in rats and the underlying mechanisms, including astrocyte autophagy and
      apoptosis in the spinal cord. Rats with CCI-induced NP were used to evaluate the
      analgesic and anti-inflammatory effects of koumine. Lipopolysaccharide (LPS)
      induced inflammation in rat primary astrocytes was also used to evaluate the anti
      inflammatory effect of koumine. We found that repeated treatment with koumine
      significantly reduced and inhibited CCI-evoked astrocyte activation as well as
      the levels of pro-inflammatory cytokines. Meanwhile, we found that koumine
      promoted autophagy in the spinal cord of CCI rats, as reflected by decreases in
      the LC3-II/I ratio and P62 expression. Double immunofluorescence staining showed
      a high level of colocalization between LC3 and GFAP-positive glia cells, which
      could be decreased by koumine. Intrathecal injection of an autophagy inhibitor
      (chloroquine) reversed the analgesic effect of koumine, as well as the inhibitory
      effect of koumine on astrocyte activation in the spinal cord. In addition, TUNEL
      staining suggested that CCI-induced apoptosis was inhibited by koumine, and this
      inhibition could be abolished by chloroquine. Western blot analysis revealed that
      koumine significantly increased the level of Bcl-xl while inhibiting Bax
      expression and decreasing cleaved caspase-3. In addition, we found that koumine
      could decrease astrocyte-mediated neuroinflammation and enhance autophagy in
      primary cultured astrocytes. These results suggest that the analgesic effects of
      koumine on CCI-induced NP may involve inhibition of astrocyte activation and pro
      inflammatory cytokine release, which may relate to the promotion of astrocyte
      autophagy and the inhibition for apoptosis in the spinal cord.

PMID- 30214412
TI  - Pharmacological Action of a Pregnane Glycoside, Russelioside B, in Dietary Obese
      Rats: Impact on Weight Gain and Energy Expenditure.
AB  - Background and purpose: Russelioside B (RB) is a pregnane glycoside obtained from
      Caralluma quadrangula; a herb with antidiabetic, anti-inflammatory, and
      antihyperlipidemic activities. The present experiment tested the possible role of
      RB in controlling weight gain in rats fed on high fat (HF) diet. Methods: RB was
      separated from the n-butanol fraction of the crude methanolic extract by
      chromatographic separation on a Si gel column according to the procedures
      described previously. The experiment of the biological assessment of RB used 32
      male Wistar rats (4 groups, n = 8). Group 1 rats were fed with a palatable normal
      diet. Group 2, 3, and 4 were fed on HF diet for 16 weeks. Group 2 served as the
      HF diet control group while Group 3 and 4 received daily oral doses of RB (25 and
      50 mg/kg) during the last four weeks. Animals' parameters like weight gain,
      fasting level of blood sugar, serum lipids, and serum liver enzyme activities
      were measured. Liver or adipose tissue weight was divided by the rat's body
      weight and multiplied by 100 to obtain the liver or adipose tissue index,
      respectively. Adipose tissues were processed for histopathological examination,
      measurement of mRNA expression of visfatin, leptin, adiponectin, uncoupling
      protein-1 (UCP-1), and carnitine palmitoyl transferase-1 (CPT-1). Furthermore,
      serum levels of insulin, interleukin-6 (IL-6), IL-1beta, tumor necrosis factor
      alpha (TNF-alpha), leptin, resistin, and adiponectin were assessed using ELISA
      kits. Results: Rats fed with the HF diet exhibited significant body weight gain,
      abnormal liver function, disturbed lipid profile, and greater serum level of pro
      inflammatory cytokines in addition to greater insulin resistance, adipose tissue
      and liver indices. Further, rats fed with the HF diet displayed upregulations in
      the expression of visfatin and leptin with downregulations in the expression of
      adiponectin, UCP-1, and CPT-1 compared to normal rats. Interestingly, RB (25 or
      50 mg/kg) favorably modulated the measured parameters. Conclusion: Data from this
      study documented the beneficial role of RB in diminishing weight gain, improving
      the inflammatory perturbations and energy expenditure in HF diet fed rats.
      Therefore, RB might be a promising candidate for obesity.

PMID- 30214413
TI  - Proceeding From in vivo Functions of Pheromone Receptors: Peripheral-Coding
      Perception of Pheromones From Three Closely Related Species, Helicoverpa
      armigera, H. assulta, and Heliothis virescens.
AB  - Three closely related species, Helicoverpa armigera, H. assulta, and Heliothis
      virescens from Lepidoptera Noctuidae, are used as a model system for exploring
      sexual communication and species isolation. Pheromone receptors (PRs) previously
      discovered in model moth species include seven in H. armigera, six in H. assulta,
      and six in H. virescens. PRs named OR6, OR13, and OR16 among these species were
      found to be functional, characterized by an in vitro Xenopus oocytes system.
      Using an in vivo transgenic fly system, functional assays of OR6, OR13, and OR16
      clades from three closely related Noctuidae species showed that OR13 function was
      highly conserved, whereas OR6 and OR16 exhibited functional divergence. Similar
      results were produced from assays in the Xenopus oocytes system. Combined with
      earlier behavioral results and electrophysiological recordings, we found
      corresponding relationships among pheromones, PRs, and neurons at the periphery
      sensory system of each species. Our results provide vital information at the
      neuronal and molecular level, shedding insight into the sexual communication of
      closely related species in Lepidoptera.

PMID- 30214414
TI  - Caenorhabditis elegans Show Preference for Stimulants and Potential as a Model
      Organism for Medications Screening.
AB  - The nematode Caenorhabditis elegans (C. elegans) is a popular invertebrate model
      organism to study neurobiological disease states. This is due in part to the
      intricate mapping of all neurons and synapses of the entire animal, the wide
      availability of mutant strains, and the genetic and molecular tools that can be
      used to manipulate the genome and gene expression. We have shown that, C. elegans
      develops a conditioned preference for cues that had previously been paired with
      either cocaine or methamphetamine exposure that is dependent on dopamine
      neurotransmission, similar to findings using place conditioning with rats and
      mice. In the current study, we show C. elegans also display a preference for, and
      self-exposure to, cocaine and nicotine. This substance of abuse (SOA) preference
      response can be selectively blocked by pretreatment with naltrexone and is
      consistent with the recent discovery of an opioid receptor system in C. elegans.
      In addition, pre-exposure to the smoking cessation treatment varenicline also
      inhibits self-exposure to nicotine. Exposure to concentrations of treatments that
      inhibit SOA preference/self-exposure did not induce any significant inhibition of
      locomotor activity or affect food or benzaldehyde chemotaxis. These data provide
      predictive validity for the development of high-throughput C. elegans behavioral
      medication screens. These screens could enable fast and accurate generation of
      data to identify compounds that may be effective in treating human addiction. The
      successful development and validation of such models would introduce powerful and
      novel tools in the search for new pharmacological treatments for substance use
      disorders, and provide a platform to study the mechanisms that underlie
      addictions.

PMID- 30214415
TI  - A New Training Assessment Method for Alpine Ski Racing: Estimating Center of Mass
      Trajectory by Fusing Inertial Sensors With Periodically Available Position Anchor
      Points.
AB  - In this study we present and validate a method to correct velocity and position
      drift for inertial sensor-based measurements in the context of alpine ski racing.
      Magnets were placed at each gate and their position determined using a land
      surveying method. The time point of gate crossings of the athlete were detected
      with a magnetometer attached to the athlete's lower back. A full body inertial
      sensor setup allowed to track the athlete's posture, and the magnet positions
      were used as anchor points to correct position and velocity drift from the
      integration of the acceleration. Center of mass (CoM) position errors (mean +/-
      standard deviation) were 0.24 m +/- 0.09 m and CoM velocity errors were 0.00 m/s
      +/- 0.18 m/s. For extracted turn entrance and exit speeds the 95% limits of
      agreements (LoAs) were between -0.19 and 0.33 m/s. LoA for the total path length
      of a turn were between -0.06 and 0.16 m. The proposed setup and processing
      allowed estimating the CoM kinematics with similar errors than known for
      differential global navigation satellite systems (GNSS), even though the
      athlete's movement was measured with inertial and magnetic sensors only.
      Moreover, as the gate positions can also be obtained with non-GNSS based land
      surveying methods, CoM kinematics may be estimated in areas with reduced or no
      GNSS signal reception, such as in forests or indoors.

PMID- 30214416
TI  - Automatic Detection of Atrial Fibrillation Based on Continuous Wavelet Transform
      and 2D Convolutional Neural Networks.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmias causing morbidity
      and mortality. AF may appear as episodes of very short (i.e., proximal AF) or
      sustained duration (i.e., persistent AF), either form of which causes irregular
      ventricular excitations that affect the global function of the heart. It is an
      unmet challenge for early and automatic detection of AF, limiting efficient
      treatment strategies for AF. In this study, we developed a new method based on
      continuous wavelet transform and 2D convolutional neural networks (CNNs) to
      detect AF episodes. The proposed method analyzed the time-frequency features of
      the electrocardiogram (ECG), thus being different to conventional AF detecting
      methods that implement isolating atrial or ventricular activities. Then a 2D CNN
      was trained to improve AF detection performance. The MIT-BIH Atrial Fibrillation
      Database was used for evaluating the algorithm. The efficacy of the proposed
      method was compared with those of some existing methods, most of which
      implemented the same dataset. The newly developed algorithm using CNNs achieved
      99.41, 98.91, 99.39, and 99.23% for the sensitivity, specificity, positive
      predictive value, and overall accuracy (ACC) respectively. As the proposed
      algorithm targets the time-frequency feature of ECG signals rather than isolated
      atrial or ventricular activity, it has the ability to detect AF episodes for
      using just five beats, suggesting practical applications in the future.

PMID- 30214417
TI  - Extracellular Vesicle Characteristics in beta-thalassemia as Potential Biomarkers
      for Spleen Functional Status and Ineffective Erythropoiesis.
AB  - beta-thalassemia major (beta-TM) is a therapeutically challenging chronic disease
      in which ineffective erythropoiesis is a main pathophysiological factor.
      Extracellular vesicles (EVs) are membrane-enclosed vesicles released by cells
      into biological fluids; they are involved in intercellular communication and in
      multiple physiological and pathological processes. The chaperone heat-shock
      protein 70 (HSP70), which is released from cells via EVs, aggravates ineffective
      erythropoiesis in beta-TM. We propose that beta-TM EVs may show specific
      signatures, reflecting disease mechanisms, stages and severity. Our study aims
      were to define EV profiles in beta-TM patients, investigate the influence of
      hypersplenism and splenectomy on EV features, and explore the association of
      circulating EVs with ineffective erythropoiesis and iron-overload parameters. We
      characterized circulating EVs in 35 transfusion-dependent beta-thalassemia
      patients and 35 controls using several techniques. Nanoparticle-tracking analysis
      revealed increased EV concentration in patients vs. controls (P = 0.0036), with
      smaller EV counts and sizes in patients with hypersplenism. Flow cytometry
      analysis showed lower levels of RBC and monocyte EVs in patients vs. controls.
      RBC-EV levels correlated with patient hematocrit, reflecting degree of anemia.
      The procoagulant potential of the EVs evaluated by flow cytometry revealed lower
      levels of endothelial protein C receptor-labeled EVs in patients vs. controls,
      and increased tissue factor-to-tissue factor pathway inhibitor-labeled EV ratio
      in splenectomized patients, suggesting a hypercoagulable state. Protein content,
      evaluated in EV pellets, showed increased levels of HSP70 in patients (P =
      0.0018), inversely correlated with transfusion requirement and hemoglobin levels,
      and positively correlated with reticulocyte, erythropoietin and lactate
      dehydrogenase levels. This first description of EVs in patients with
      hypersplenism reveals the spleen's importance in EV physiology and clearance.
      Circulating EV-HSP70 levels were associated with markers of ineffective
      erythropoiesis, hemolysis and hematological disease severity. EV analysis in beta
      TM-reflecting spleen status, hypercoagulability state and ineffective
      erythropoiesis-may serve as a biomarker of disease dynamics, supporting both
      anticipation of the risk of complications and optimizing treatment.

PMID- 30214419
TI  - Corrigendum: Real-Time Rotational Activity Detection in Atrial Fibrillation.
AB  - [This corrects the article DOI: 10.3389/fphys.2018.00208.].

PMID- 30214418
TI  - Proteomic Identification of Novel Plasma Biomarkers and Pathobiologic Pathways in
      Alcoholic Acute Pancreatitis.
AB  - Acute pancreatitis (AP) is a painful and potentially life-threatening disorder
      with the potential for therapeutic interventions. Biomarkers that characterize
      cases by severity and pathogenic mechanisms involved are not yet available but
      needed for the implementation of rational therapies. Here, we used shotgun
      proteomics to obtain information from plasma samples about local and systemic
      pathologies taking place during cases of alcoholic AP. Plasma was obtained at
      Kaunas University of Medicine Hospital (Lithuania) from 12 AP patients of alcohol
      related etiology (median age of 40) within 24 h of presentation, and 12 age
      matched, healthy controls. Patients entered into the study had moderately severe
      AP with the following characteristics: mean blood lactate dehydrogenase level of
      1127 mg/dl; median APACHEII score of 5.5 and mean IMRIE score of 3.5. For
      proteomic analysis, less-abundant proteins in plasma samples were enriched using
      Top 12 abundant protein depletion columns. Further processing was performed by a
      modified filter-assisted sample preparation combined with tandem mass tag
      labeling for quantitation. Samples were analyzed using an Orbitrap Elite mass
      spectrometer for high resolution liquid chromatography-tandem mass spectrometry
      (LC-MS/MS). Our analysis revealed 31 proteins that exhibited significant 1.5-fold
      or higher increases in the AP compared to control patients, and six that were
      significantly decreased. Gene ontology analysis indicated a strong correlation
      with exosomal origin in the elevated proteins, with 29/31 (93.5%) associated with
      this extracellularly-secreted compartment. Elevated proteins included established
      and proposed biomarkers of AP including C-reactive protein, LPS-binding protein,
      intercellular adhesion molecule-1, and von Willebrand factor, as well as several
      novel potential biomarkers. These results provide the methodology for proteomic
      analysis of plasma samples to discover novel biomarkers that characterize
      pancreatitis cases by pathogenic mechanism as well as disease activity at an
      early stage that is highly informative for routine clinical practice and clinical
      trials.

PMID- 30214420
TI  - Beyond Exposure to Outdoor Nature: Exploration of the Benefits of a Green
      Building's Indoor Environment on Wellbeing.
AB  - Most research exploring the psychological benefits of the natural environment has
      focused on direct exposure to the outdoors. However, people spend most of their
      time indoors, particularly in office buildings. Poor employee mental health has
      become one the most prevalent and costly occupational health issues. The
      integration of high quality environmental features (e.g., access to sunlight) in
      green-certified office buildings offers a superior work environment. These nature
      based experiences are anticipated to provide beneficial outcomes to wellbeing.
      This study is the first to empirically investigate these benefits. Participants
      in a green (LEED gold certified) office building (N = 213) in Canada completed an
      assessment of environmental features, measures of hedonic, eudaimonic and
      negative wellbeing (NWB) and assessments of psycho-environmental potential,
      environmental behaviors and social belonging. Linear regression analyses
      confirmed the benefits of indoor environmental features for all aspects of
      wellbeing. Multiple regression analyses were conducted to assess the effect of
      specific indoor environmental features on wellbeing. We explored physical
      features (e.g., air quality, light), and social features (e.g., privacy), as well
      as windows to the outside. Results suggest that physical features are important
      in promoting hedonic wellbeing, while social features prevent NWB. Both features
      equally predicted eudaimonic wellbeing (EWB). A view to the outside was
      positively correlated to wellbeing, although it did not uniquely predict it after
      accounting for other environmental features. Path analyses revealed the
      importance of person-environment fit, pro-environmental behavior and social
      belonging in mediating the association of indoor environmental features with
      hedonic and EWB. The results suggests that, by fostering person-environment fit,
      pro-environmental behaviors and feeling of community in a high quality setting,
      green buildings may lead to benefits on an array of wellbeing dimensions. The
      theoretical and practical implications of these findings are discussed.

PMID- 30214421
TI  - Targeting Procrastination Using Psychological Treatments: A Systematic Review and
      Meta-Analysis.
AB  - Background: Procrastination can be stressful and frustrating, but it seldom
      causes any major distress. However, for some people, it can become problematic,
      resulting in anxiety, lowered mood, physical complaints, and decreased well
      being. Still, few studies have investigated the benefits of targeting
      procrastination. In addition, no attempt has previously been made to determine
      the overall efficacy of providing psychological treatments. Methods: A systematic
      review and meta-analysis was conducted by searching for eligible records in
      Scopus, Proquest, and Google Scholar. Only randomized controlled trials comparing
      psychological treatments for procrastination to an inactive comparator and
      assessing the outcomes by a self-report measure were included. A random effects
      model was used to determine the standardized mean difference Hedge's g at post
      treatment. Furthermore, test for heterogeneity was performed, fail-safe N was
      calculated, and the risk of bias was explored. The study was pre-registered at
      Prospero: CRD42017069981. Results: A total of 1,639 records were identified, with
      12 studies (21 comparisons, N = 718) being included in the quantitative
      synthesis. Overall effect size g when comparing treatment to control was 0.34,
      95% Confidence Interval [0.11, 0.56], but revealing significant heterogeneity,
      Q(20) = 46.99, p < 0.00, and I2 = 61.14%, 95% CI [32.83, 84.24]. Conducting a
      subgroup analysis of three out of four studies using cognitive behavior therapy
      (CBT) found an effect size g of 0.55, 95% CI [0.32, 0.77], and no longer showing
      any heterogeneity, Q(4) = 3.92, p = 0.42, I2 = 0.00%, 95% CI [0.00, 91.02] (N =
      236). Risk of publication bias, as assessed by the Egger's test was not
      significant, z = -1.05, p = 0.30, fail-safe N was 370 studies, and there was some
      risk of bias as rated by two independent researchers. In terms of secondary
      outcomes, the self-report measures were too varied to present an aggregated
      estimate. Conclusions: Psychological treatments seem to have small benefits on
      procrastination, but the studies displayed significant between-study variation.
      Meanwhile, CBT was associated with a moderate benefit, but consisted of only
      three studies. Recommendations for future research are provided, including the
      use of more valid and reliable outcomes and a screening interview at intake.

PMID- 30214423
TI  - How Is Learning Motivation Shaped Under Different Contexts: An Ethnographic Study
      in the Changes of Adult Learner's Motivational Beliefs and Behaviors Within a
      Foreign Language Course.
AB  - There has been a burgeoning interest of students' motivational beliefs in
      determining their motivational behaviors in classroom activities: choice of task
      and persistence of task. Previous research mostly used quantitative methods to
      understand students' general motivation, without taking contextual factors into
      consideration. To fill in this gap, the present study examined the influence of
      changing contexts on students' motivational beliefs in a Chinese language
      classroom, and how those changes in motivational beliefs shaped their
      motivational behaviors in class activities. An ethnographic multiple-case study
      approach was adopted, and six adult learners were chosen from a Chinese language
      course in a Hong Kong university. On-going semi-structured interviews, class
      observations, stimulated recall and document reviews were conducted to understand
      student development across time. Findings show that the more proficient students
      were showing relatively stable motivational beliefs as well as behaviors
      throughout the foreign language course. In contrast, the less proficient students
      were demonstrating obvious changes in their motivational beliefs and hence
      behaviors, due to the different contexts of non-exam and high-stake exam. The
      study suggested students' learning motivation in class was context-dependent, and
      could fluctuate substantially on a weekly basis. Those dynamic within-course
      changes at different learning stages and the reasons shaping the changes could
      give pedagogical insights to the teacher with adult learners.

PMID- 30214422
TI  - Sex Differences in Spontaneous Brain Activity in Adolescents With Conduct
      Disorder.
AB  - Purpose: Sex differences in conduct disorder (CD) pathophysiology have yet to be
      resolved. In this study, we applied the amplitude of low-frequency fluctuations
      (ALFF) and fractional ALFF (fALFF) to compare spontaneous brain activity in male
      versus female adolescents diagnosed with CD in light of the gender paradox
      hypothesis. Materials and Methods: Resting-state functional magnetic resonance
      imaging (rs-fMRI) examinations were conducted with 51 CD patients (35 males) and
      53 age-matched healthy controls (HCs; 35 males). Pearson analysis was conducted
      to detect relationship between ALFF/fALFF values in gender-differentiated regions
      and clinical characteristics. Results: We observed that male CD patients showed
      significant increased ALFF in the bilateral superior temporal gyrus (STG)/insula,
      and significant decreased ALFF in the left anterior cingulate cortex (ACC), left
      middle frontal gyrus (BA8 andBA11), left middle temporal gyrus and left
      inferior/middle temporal gyrus relative to female CD patients. The fALFF in male
      CD patients was significantly increased in the right STG/insula, decreased in the
      right superior frontal gyrus, left middle frontal gyrus, right inferior frontal
      gyrus, and right postcentral gyrus relative to female CD patients. Considering
      the sex-by-diagnosis interactions in CD patients, the male CD patients had
      significantly higher fALFF in the left putamen, lower fALFF in the right
      postcentral gyrus relative to the female CD patients. Conclusion: The brain
      regions whose activity index values differed in relation to sex should be further
      explored in CD pathophysiology studies, particularly with respect to sex
      differences in clinical symptoms, emotional features, cognitive features, and
      prevalence rates in CD. The present findings are consistent with the gender
      paradox hypothesis.

PMID- 30214424
TI  - Reversible Valproate-Induced Subacute Encephalopathy Associated With a MT-ATP8
      Variant in the Mitochondrial Genome.
AB  - Introduction: There are several reported cases of patients developing motor and
      cognitive neurological impairment under treatment with valproic acid (VPA). We
      describe a woman who developed a subacute encephalopathy after VPA intake,
      harboring a mitochondrial DNA variant, previously described as causing VPA
      sensitivity in one pediatric patient. Material and Methods: A 65-year old woman
      developed a progressive, severe neurological deterioration after a 3 month
      treatment with valproate sodium, 800 mg daily. Magnetic resonance spectroscopy
      (MRS), muscle histochemical analysis and assay of mitochondrial enzymatic
      activities, and mitochondrial DNA sequencing were performed. Results:
      Neurological examination showed drowsiness, vertical gaze palsy, inability to
      either stand or walk, diffuse weakness, increased tendon reflexes. Blood lactate
      was increased, EEG showed diffuse theta and delta activity, MRI subcortical
      atrophy and leukoencephalopathy, MRS marked reduction of the NAA spectrum, with a
      small signal compatible with presence of lactate. Muscle biopsy evidenced
      presence of ragged red fibers (20%) and reduced COX reactivity. Assay of the
      muscle enzymatic activities showed multiple deficiencies of the electron
      transport chain and reduced ATP production. The mt.8393C>T variant in the MT-ATP8
      gene was found in homoplasmy. The patient considerably improved after valproate
      withdrawal. Conclusion: The variant we found has been reported both as a
      polymorphism and, in a single patient, as related to the valproate-induced
      encephalopathy. The present case is the first bearing this mutation in
      homoplasmy. In case of neurological symptoms after starting VPA therapy, once
      hyperammonemia and liver failure have been ruled out, mtDNA abnormalities should
      be considered.

PMID- 30214425
TI  - Restless Legs Syndrome in Chinese Patients With Sporadic Amyotrophic Lateral
      Sclerosis.
AB  - Objective: To evaluate the frequency and clinical features of restless legs
      syndrome (RLS) in a group of Chinese patients with amyotrophic lateral sclerosis
      (ALS). Methods: 109 Patients included in this study fulfilled the revised El
      Escorial diagnostic criteria for clinically definite, probable and lab-supported
      probable ALS, and a group of 109 control subjects was matched for age and sex to
      the ALS group. Disease severity was assessed by the revised ALS functional rating
      scale (ALSFRS-R). The diagnosis of RLS was made according to the criteria of the
      International RLS Study Group. Other characteristics including sleep quality,
      excessive daytime sleepiness (EDS), REM sleep behavior disorder (RBD), depression
      and anxiety were also evaluated in ALS patients. Results: RLS was significantly
      more frequent in ALS patients than in control subjects (14.6 vs. 0.9%; P < 0.05).
      Compared to those without RLS, ALS patients with RLS reported a higher frequency
      of anxiety and EDS. ALS patients with RLS showed more severe legs dysfunction.
      EDS and legs function scores of the ALSFRS-R were independent factors
      significantly associated with RLS in ALS patients. Conclusions: Our findings
      suggest that Chinese ALS patients exhibit a high frequency of RLS symptoms and
      that these patients may benefit from recognition of the condition and optimized
      management of its symptoms. Moreover, ALS patients might cause circadian rhythms
      disturbance and our study further supports that ALS is a heterogeneous disorder
      involving multiple systems; further studies are needed to confirm these
      preliminary findings.

PMID- 30214427
TI  - Genome-Wide Analysis on the Landscape of Transcriptomes and Their Relationship
      With DNA Methylomes in the Hypothalamus Reveals Genes Related to Sexual Precocity
      in Jining Gray Goats.
AB  - The Jining Gray goat is famous for its sexual precocity; however, the exact
      regulatory mechanism is still unknown. The hypothalamus is the key centrum in the
      process of animal reproduction, especially in signal transduction, and the
      initiation of puberty. The identification of potential genes and pathways in the
      hypothalamus of Jining Gray goat is critical to understanding the regulatory
      mechanism of sexual precocity in these goats. In this study, mRNA transcriptome
      analysis of the hypothalamus of juvenile and pubertal goats revealed eight genes
      (NTS, ADORA1, CRH, UCN3, E2F2, PDGFRB, GNRH1, and CACNA1C) and three pathways
      [neuroactive ligand-receptor interaction; gonadotropin-releasing hormone (GnRH)
      signal; melanoma] that are involved in this regulation. Subsequent methylation
      analysis on differentially methylated region (DMR) genes revealed the potential
      regulation network that influences pubertal onset. Correlation analysis verified
      the methylation level of some DMR genes correlates negatively with expression
      level. Integrated analysis between transcriptomes and methylomes identified 80
      candidate genes involved in GnRH and neuroactive ligand signal pathways, of which
      CACNA1C and CRH were differentially expressed genes (DEGs) influenced by
      methylation level. The GnRH gene was the only DEG not affected by its methylation
      level. In summary, in this study, we identified eight genes and three pathways
      that are related to pubertal onset in Jining Gray goats, and the expression of
      CACNA1C and CRH genes of the GnRH and neuroactive ligand signal pathways were
      influenced by DNA methylation, while that of the GnRH gene was not affected.

PMID- 30214426
TI  - Insulin-Like Growth Factor Binding Proteins in Autoimmune Diseases.
AB  - Insulin-like growth factor binding proteins (IGFBPs) are a family of proteins
      binding to Insulin-like growth factors (IGFs), generally including IGFBP1,
      IGFBP2, IGFBP3, IGFBP4, IGFBP5, and IGFBP6. The biological functions of IGFBPs
      can be classified as IGFs-dependent actions and IGFs-independent effects. In this
      review, we will discuss the structure and function of various IGFBPs,
      particularly IGFBPs as potential emerging biomarkers and therapeutic targets in
      various autoimmune diseases, and the possible mechanisms by which IGFBPs act on
      the pathogenesis of autoimmune diseases.

PMID- 30214430
TI  - Corrigendum: Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A
      Key Role for Pregnancy- Associated Plasma Protein-A.
AB  - [This corrects the article DOI: 10.3389/fendo.2018.00031.].

PMID- 30214428
TI  - The Role of Hepatocyte Growth Factor (HGF) in Insulin Resistance and Diabetes.
AB  - In obesity, insulin resistance (IR) and diabetes, there are proteins and hormones
      that may lead to the discovery of promising biomarkers and treatments for these
      metabolic disorders. For example, these molecules may impair the insulin
      signaling pathway or provide protection against IR. Thus, identifying proteins
      that are upregulated in IR states is relevant to the diagnosis and treatment of
      the associated disorders. It is becoming clear that hepatocyte growth factor
      (HGF) is an important component of the pathophysiology of IR, with increased
      levels in most common IR conditions, including obesity. HGF has a role in the
      metabolic flux of glucose in different insulin sensitive cell types; plays a key
      role in beta-cell homeostasis; and is capable of modulating the inflammatory
      response. In this review, we discuss how, and to what extent HGF contributes to
      IR and diabetes pathophysiology, as well as its role in cancer which is more
      prevalent in obesity and diabetes. Based on the current literature and knowledge,
      it is clear that HGF plays a central role in these metabolic disorders. Thus, HGF
      levels could be employed as a biomarker for disease status/progression, and HGF/c
      Met signaling pathway modulators could effectively regulate IR and treat
      diabetes.

PMID- 30214429
TI  - Variant Alleles of the ESR1, PPARG, HMGA2, and MTHFR Genes Are Associated With
      Polycystic Ovary Syndrome Risk in a Chinese Population: A Case-Control Study.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of
      reproductive age, with a prevalence of 6-8%. Although the etiology of PCOS has
      been investigated extensively, the association between genetic predisposition and
      PCOS risk is largely unknown. In this study, we genotyped 63 SNPs in 10 genes
      among 361 PCOS patients and 331 healthy controls in a Chinese Han population. The
      following variant alleles were significantly associated with decreased PCOS risk:
      ESR1 rs9340799 (P = 0.000), PPARG rs709154 (P = 0.013), and rs1151996 (P =
      0.013), HMGA2 rs2272046 (P = 0.000), MTHFR rs1801133 (P = 0.000). Accordingly,
      the following genotypes at various loci were associated with reduced PCOS risk:
      GA genotype at rs9340799 (P < 0.0001) in ESR1, TA genotype at rs709154(P <
      0.0001) in PPARG and CA genotype at rs2272046 (P < 0.0001) in HMGA2. Moreover, GA
      genotype at rs1999805 (P = 0.013) in ESR1 and TT genotype at rs1801133 in MTHFR
      (P < 0.0001) correlated with elevated PCOS risk. Furthermore, haplotype analysis
      revealed significant differences in haplotype distributions of CYP11A1, ESR2 and
      PPARG gene between cases and controls. In addition to confirming that ESR1
      rs9340799, HMGA2 rs2272046 and MTHFR rs1801133 are related to the risk of PCOS,
      these findings also provide the first evidence that PPARG rs709154 and ESR1
      rs1999805 are significantly associated with PCOS risk in a Chinese population.
      Further functional studies are warranted to elucidate the underlying biological
      mechanisms.

PMID- 30214432
TI  - Multispecies Biofilm Development of Marine Bacteria Implies Complex Relationships
      Through Competition and Synergy and Modification of Matrix Components.
AB  - Microbial communities composition is largely shaped by interspecies competition
      or cooperation in most environments. Ecosystems are made of various dynamic
      microhabitats where microbial communities interact with each other establishing
      metabolically interdependent relationships. Very limited information is available
      on multispecies biofilms and their microhabitats related to natural environments.
      The objective of this study is to understand how marine bacteria isolated from
      biofilms in the Mediterranean Sea interact and compete with each other when
      cultivated in multispecies biofilms. Four strains (Persicivirga mediterranea TC4,
      Polaribacter sp. TC5, Shewanella sp. TC10 and TC11) with different phenotypical
      traits and abilities to form a biofilm have been selected from a previous study.
      Here, the results show that these strains displayed a different capacity to form
      a biofilm in static versus dynamic conditions where one strain, TC11, was highly
      susceptible to the flux. These bacteria appeared to be specialized in the
      secretion of one or two exopolymers. Only TC5 seemed to secrete inhibitory
      molecule(s) in its supernatant, with a significant effect on TC10. Most of the
      strains negatively impacted each other, except TC4 and TC10, which presented a
      synergetic effect in the two and three species biofilms. Interestingly, these two
      strains produced a newly secreted compound when grown in dual-species versus mono
      species biofilms. TC5, which induced a strong inhibition on two of its partners
      in dual-species biofilms, outfitted the other bacteria in a four-species biofilm.
      Therefore, understanding how bacteria respond to interspecific interactions
      should help comprehending the dynamics of bacterial populations in their
      ecological niches.

PMID- 30214431
TI  - Divergence of Fecal Microbiota and Their Associations With Host Phylogeny in
      Cervinae.
AB  - Gastrointestinal microbiota may shape the adaptation of their hosts to different
      habitats and lifestyles, thereby driving their evolutionary diversification. It
      remains unknown if gastrointestinal microbiota diverge in congruence with the
      phylogenetic relationships of their hosts. To evaluate the phylosymbiotic
      relationships, here we analyzed the compositions of fecal microbiota of seven
      Cervinae species raised in the Chengdu Zoo. All sampled animals were kept in the
      same environmental condition and fed identical fodder for years. Results showed
      that Firmicutes and Bacteroidetes were dominant in their fecal microbiota. Even
      though some bacteria (e.g., Ruminococcaceae) were found to be common in the feces
      of all investigated species, some genera (e.g., Sharpea and Succinivibrio) were
      only observed in animals with particular digestive systems. As for the
      intraspecies variations of microbial communities, only a few operational
      taxonomic units (OTUs) were shared among replicates of the same host species
      although they accounted for most of the total abundance. Correlation was observed
      between the fecal microbiota divergence and host phylogeny, but they were not
      congruent completely. This may shed new light on the coevolution of host species
      and their microbiota.

PMID- 30214433
TI  - Comparative Genomics Reveal a Flagellar System, a Type VI Secretion System and
      Plant Growth-Promoting Gene Clusters Unique to the Endophytic Bacterium Kosakonia
      radicincitans.
AB  - The recent worldwide discovery of plant growth-promoting (PGP) Kosakonia
      radicincitans in a large variety of crop plants suggests that this species
      confers significant influence on plants, both in terms of yield increase and
      product quality improvement. We provide a comparative genome analysis which helps
      to unravel the genetic basis for K. radicincitans' motility, competitiveness and
      plant growth-promoting capacities. We discovered that K. radicincitans carries
      multiple copies of complex gene clusters, among them two flagellar systems and
      three type VI secretion systems (T6SSs). We speculate that host invasion may be
      facilitated by different flagella, and bacterial competitor suppression by
      effector proteins ejected via T6SSs. We found a large plasmid in K. radicincitans
      DSM 16656T, the species type strain, that confers the potential to exploit plant
      derived carbon sources. We propose that multiple copies of complex gene clusters
      in K. radicincitans are metabolically expensive but provide competitive advantage
      over other bacterial strains in nutrient-rich environments. The comparison of the
      DSM 16656T genome to genomes of other genera of enteric plant growth-promoting
      bacteria (PGPB) exhibits traits unique to DSM 16656T and K. radicincitans,
      respectively, and traits shared between genera. We used the output of the in
      silico analysis for predicting the purpose of genomic features unique to K.
      radicincitans and performed microarray, PhyloChip, and microscopical analyses to
      gain deeper insight into the interaction of DSM 16656T, plants and associated
      microbiota. The comparative genome analysis will facilitate the future search for
      promising candidates of PGPB for sustainable crop production.

PMID- 30214434
TI  - Plasma Circular RNAs hsa_circ_0001953 and hsa_circ_0009024 as Diagnostic
      Biomarkers for Active Tuberculosis.
AB  - Recent studies have demonstrated that circular RNAs (circRNAs) could serve as
      potential molecular markers for disease diagnosis; however, little is known about
      their diagnostic value in active tuberculosis (TB). This study first performed a
      microarray screening of circRNA changes in plasma samples from 3 patients with
      active pulmonary TB and 3 healthy controls. Then, candidate circRNAs were
      selected for validation on a quantitative real-time PCR system. Of the 61
      differentially expressed circRNAs recorded, 43 and 18 were upregulated and
      downregulated in the TB group, respectively. Validation assays demonstrated that
      plasma levels of 6 circRNAs, including hsa_circ_0009024, hsa_circ_0001953,
      hsa_circ_0008297, hsa_circ_0003528, hsa_circ_0003524 and hsa_circ_0015879 were
      remarkably increased in TB patients. Plasma levels of hsa_circ_0001953 and
      hsa_circ_0009024 were correlated with TB severity. Next, hsa_circ_0001953 and
      hsa_circ_0009024 were assessed in an independent cohort consisting of 120 TB
      patients and 100 control individuals. An area under the receiver operating
      characteristic (ROC) curve of 0.915 (95% confidence interval 0.880-0.951; P <
      0.001) was obtained for detecting TB, with hsa_circ_0001953 and hsa_circ_0009024
      used in combination. Additionally, plasma levels of hsa_circ_0001953 and
      hsa_circ_0009024 were reduced significantly in patients after treatment (P <
      0.001). The present findings indicate that the circRNAs hsa_circ_0001953 and
      hsa_circ_0009024 may represent novel plasma biomarkers for active TB diagnosis.

PMID- 30214435
TI  - The RNA Complement of Outer Membrane Vesicles From Salmonella enterica Serovar
      Typhimurium Under Distinct Culture Conditions.
AB  - Bacterial outer membrane vesicles (OMVs), as well as OMV-associated small RNAs,
      have been demonstrated to play a role in host-pathogen interactions. The presence
      of larger RNA transcripts in OMVs has been less studied and their potential role
      in host-pathogen interactions remains largely unknown. Here we analyze RNA from
      OMVs secreted by Salmonella enterica serovar Typhimurium (S. Typhimurium)
      cultured under different conditions, which mimic host-pathogen interactions. S.
      Typhimurium was grown to exponential and stationary growth phases in minimal
      growth control medium (phosphate-carbon-nitrogen, PCN), as well as in acidic and
      phosphate-depleted PCN, comparable to the macrophage environment and inducing
      therefore the expression of Salmonella pathogenicity island 2 (SPI-2) genes.
      Moreover, Salmonella pathogenicity island 1 (SPI-1), which is required for
      virulence during the intestinal phase of infection, was induced by culturing S.
      Typhimurium to the stationary phase in Lysogeny Broth (LB). For each condition,
      we identified OMV-associated RNAs that are enriched in the extracellular
      environment relative to the intracellular space. All RNA classes could be
      observed, but a vast majority of rRNA was exported in all conditions in variable
      proportions with a notable decrease in LB SPI-1 inducing media. Several mRNAs and
      ncRNAs were specifically enriched in/on OMVs dependent on the growth conditions.
      Important to note is that some RNAs showed identical read coverage profiles
      intracellularly and extracellularly, whereas distinct coverage patterns were
      observed for other transcripts, suggesting a specific processing or degradation.
      Moreover, PCR experiments confirmed that distinct RNAs were present in or on OMVs
      as full-length transcripts (IsrB-1/2; IsrA; ffs; SsrS; CsrC; pSLT035; 10Sa; rnpB;
      STM0277; sseB; STM0972; STM2606), whereas others seemed to be rather present in a
      processed or degraded form. Finally, we show by a digestion protection assay that
      OMVs are able to prevent enzymatic degradation of given full-length transcripts
      (SsrS, CsrC, 10Sa, and rnpB). In summary, we show that OMV-associated RNA is
      clearly different in distinct culture conditions and that at least a fraction of
      the extracellular RNA is associated as a full-length transcripts with OMVs,
      indicating that some RNAs are protected by OMVs and thereby leaving open the
      possibility that those might be functionally active.

PMID- 30214436
TI  - Global Environmental Nontuberculous Mycobacteria and Their Contemporaneous Man
      Made and Natural Niches.
AB  - Seminal microbiological work of environmental nontuberculous mycobacteria (NTM)
      includes the discovery that NTM inhabit water distribution systems and soil, and
      that the species of NTM found are geographically diverse. It is likely that
      patients acquire their infections from repeated exposures to their environments,
      based on the well-accepted paradigm that water and soil bioaerosols - enriched
      for NTM - can be inhaled into the lungs. Support comes from reports demonstrating
      NTM isolated from the lungs of patients are genetically identical to NTM found in
      their environment. Well documented sources of NTM include peat-rich soils,
      natural waters, drinking water, hot water heaters, refrigerator taps, catheters,
      and environmental amoeba. However, NTM have also been recovered in biofilms from
      ice machines, heated nebulizers, and heater-cooler units, as well as seat dust
      from theaters, vacuum cleaners, and cobwebs. New studies on the horizon aim to
      significantly expand the current knowledge of environmental NTM niches in order
      to improve our current understanding of the specific ecological factors driving
      the emergence of NTM lung disease. Specifically, the Hawaiian Island environment
      is currently being studied as a model to identify other point sources of exposure
      as it is the U.S. state with the highest number of NTM lung disease cases.
      Because of its geographic isolation and unique ecosystem, the Hawaiian
      environment is being probed for correlative factors that may promote
      environmental NTM colonization.

PMID- 30214437
TI  - Antagonistic Interaction of Staphylococcus aureus Toward Candida glabrata During
      in vitro Biofilm Formation Is Caused by an Apoptotic Mechanism.
AB  - Background: Infections caused by Candida species and Staphylococcus aureus are
      associated with biofilm formation. C. albicans-S. aureus interactions are
      synergistic due to the significant increase in mixed biofilms and improved
      resistance to vancomycin of S. aureus. C. glabrata and S. aureus both are
      nosocomial pathogens that cause opportunistic infections in similar host niches.
      However, there is scarce information concerning the interaction between these
      last microorganisms. Results: The relationship between C. glabrata and S. aureus
      was evaluated by estimating the viability of both microorganisms in co-culture of
      planktonic cells and in single and mixed biofilms. An antagonistic behavior of S.
      aureus and their cell-free bacterial supernatant (CFBS) toward C. glabrata, both
      in planktonic form and in biofilms, was demonstrated. Scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and confocal laser
      scanning microscopy (CLSM) images showed yeast cells surrounded by bacteria,
      alterations in intracytoplasmic membranes, and non-viable blastoconidia with
      intact cell walls. Concomitantly, S. aureus cells remained viable and unaltered.
      The antagonistic activity of S. aureus toward C. glabrata was not due to cell-to
      cell contact but the presence of CFBS, which causes a significant decrement in
      yeast viability and the formation of numerous lipid droplets (LDs), reactive
      oxygen species (ROS) accumulation, as well as nuclear alterations, and DNA
      fragmentation indicating the induction of an apoptotic mechanism. Conclusion: Our
      results demonstrate that the S. aureus CFBS causes cell death in C. glabrata by
      an apoptotic mechanism.

PMID- 30214439
TI  - Design and Application of a Low pH Upflow Biofilm Sulfidogenic Bioreactor for
      Recovering Transition Metals From Synthetic Waste Water at a Brazilian Copper
      Mine.
AB  - A sulfidogenic bioreactor, operated at low pH (4-5), was set up and used to
      remove transition metals (copper, nickel, cobalt, and zinc) from a synthetic mine
      water, based on the chemistry of a moderately acidic (pH 5) drainage stream at an
      operating copper mine in Brazil. The module was constructed as an upflow biofilm
      reactor, with microorganisms immobilized on porous glass beads, and was operated
      continuously for 462 days, during which time the 2 L bioreactor processed >2,000
      L of synthetic mine water. The initial treatment involved removing copper (the
      most abundant metal present) off-line in a stream of H2S-containing gas generated
      by the bioreactor, which caused the synthetic mine water pH to fall to 2.1. The
      copper-free water was then amended with glycerol (the principal electron donor),
      yeast extract and basal salts, and pumped directly into the bioreactor where the
      other three transition metals were precipitated (also as sulfides), concurrent
      with increased solution pH. Although some acetate was generated, most of the
      glycerol fed to the bioreactor was oxidized to carbon dioxide, and was coupled to
      the reduction of sulfate to hydrogen sulfide. No archaea or eukaryotes were
      detected in the bioreactor microbial community, which was dominated by
      acidophilic sulfate-reducing Firmicutes (Peptococcaceae strain CEB3 and
      Desulfosporosinus acididurans); facultatively anaerobic non-sulfidogens
      (Acidithiobacillus ferrooxidans and Actinobacterium strain AR3) were also found
      in small relative abundance. This work demonstrated how a single low pH
      sulfidogenic bioreactor can be used to remediate a metal-rich mine water, and to
      facilitate the recovery (and therefore recycling) of target metals. The system
      was robust, and was operated empirically by means of pH control. Comparison of
      costs of the main consumables (glycerol and yeast extract) and the values of the
      metals recovered showed a major excess of the latter, supporting the view that
      sulfidogenic biotechnology can have significant economic as well as environmental
      advantages over current approaches used to remediate mine waters which produce
      secondary toxic wastes and fail to recover valuable metals.

PMID- 30214438
TI  - The Impact of Gluten Friendly Flour on the Functionality of an Active Drink:
      Viability of Lactobacillus acidophilus in a Fermented Milk.
AB  - The Gluten FriendlyTM Technology is an innovative method that induces structural
      changes in gluten proteins. In this paper a synbiotic fermented milk, containing
      Lactobacillus acidophilus La-5 and Gluten Friendly Flour (GFF), was proposed. A
      mixture design was used to combine flour, temperature and probiotic to study the
      effects of these variables on the acidification. The experiments were done on
      both GFF and control flour (CF). Thus, the following conditions were chosen to
      produce the fermented milk: L. acidophilus at 6.5 log cfu/ml; flour at 2.5 g/l;
      temperature at 37 degrees C. Then, the fermented milk was produced and stored at
      4 degrees C for 90 days. The most important result was the positive effect of GFF
      on the viability of the probiotic, with a prolongation of the shoulder length to
      20 days (12-13 days in the control). Moreover, GFF did not act on the sensory
      scores and on the physico-chemical parameters.

PMID- 30214440
TI  - Promotion of Para-Chlorophenol Reduction and Extracellular Electron Transfer in
      an Anaerobic System at the Presence of Iron-Oxides.
AB  - Anaerobic dechlorination of chlorophenols often subjects to their toxicity and
      recalcitrance, presenting low loading rate and poor degradation efficiency. In
      this study, in order to accelerate p-chlorophenol (p-CP) reduction and
      extracellular electron transfer in an anaerobic system, three iron-oxide
      nanoparticles, namely hematite, magnetite and ferrihydrite, were coupled into an
      anaerobic system, with the performance and underlying role of iron-oxide
      nanoparticles elucidated. The reductive dechlorination of p-CP was notably
      improved in the anaerobic systems coupled by hematite and magnetite, although
      ferrihydrite did not plays a positive role. Enhanced dechlorination of p-CP in
      hematite or magnetite coupled anaerobic system was linked to the obvious
      accumulation of acetate, lower oxidation-reduction potential and pH, which were
      beneficial for reductive dechlorination. Electron transfer could be enhanced by
      Fe2+/Fe3+ redox couple on the iron oxides surface formed through dissimilatory
      iron-reduction. This study demonstrated that the coupling of iron-oxide
      nanoparticles such as hematite and magnetite could be a promising alternative to
      the conventional anaerobic reduction process for the removal of CPs from
      wastewater.

PMID- 30214441
TI  - Paraburkholderia phytofirmans PsJN-Plants Interaction: From Perception to the
      Induced Mechanisms.
AB  - The use of plant-associated bacteria has received many scientific and economic
      attention as an effective and alternative method to reduce the chemical
      pesticides use in agriculture. The genus Burkholderia includes at least 90
      species including pathogenic strains, plant pathogens, as well as plant
      beneficial species as those related to Paraburkholderia, which has been reported
      to be associated with plants and exerts a positive effect on plant growth and
      fitness. Paraburkholderia phytofirmans PsJN, a beneficial endophyte able to
      colonize a wide range of plants, is an established model for plant-associated
      endophytic bacteria. Indeed, in addition to its plant growth promoting ability,
      it can also induce plant resistance against biotic as well as abiotic stresses.
      Here, we summarized an inventory of knowledge on PsJN-plant interaction, from the
      perception to the resistance mechanisms induced in the plant by a way of the
      atypical colonization mode of this endophyte. We also have carried out an
      extensive genome analysis to identify all gene clusters which contribute to the
      adaptive mechanisms under different environments and partly explaining the high
      ecological competence of P. phytofirmans PsJN.

PMID- 30214443
TI  - Xenogeneic Graft-Versus-Host Disease in Humanized NSG and NSG-HLA-A2/HHD Mice.
AB  - Despite the increasing use of humanized mouse models to study new approaches of
      graft-versus-host disease (GVHD) prevention, the pathogenesis of xenogeneic GVHD
      (xGVHD) in these models remains misunderstood. The aim of this study is to
      describe this pathogenesis in NOD/LtSz-PrkdcscidIL2rgammatm1Wjl (NSG) mice
      infused with human PBMCs and to assess the impact of the expression of HLA-A0201
      by NSG mice cells (NSG-HLA-A2/HHD mice) on xGVHD and graft-versus-leukemia (GvL)
      effects, by taking advantage of next-generation technologies. We found that T
      cells recovered from NSG mice after transplantation had upregulated expression of
      genes involved in cell proliferation, as well as in TCR, co-stimulatory, IL
      2/STAT5, mTOR and Aurora kinase A pathways. T cells had mainly an effector memory
      or an effector phenotype and exhibited a Th1/Tc1-skewed differentiation. TCRbeta
      repertoire diversity was markedly lower both in the spleen and lungs (a xGVHD
      target organ) than at infusion. There was no correlation between the frequencies
      of specific clonotypes at baseline and in transplanted mice. Finally, expression
      of HLA-A0201 by NSG mice led to more severe xGVHD and enhanced GvL effects toward
      HLA-A2+ leukemic cells. Altogether our data demonstrate that the pathogenesis of
      xGVHD shares important features with human GVHD and that NSG-HLA-A2/HHD mice
      could serve as better model to study GVHD and GvL effects.

PMID- 30214444
TI  - ATF3 Stimulates IL-17A by Regulating Intracellular Ca2+/ROS-Dependent IL-1beta
      Activation During Streptococcus pneumoniae Infection.
AB  - Activating transcription factor-3 (ATF3) in the ER stress pathway induces
      cytokine production and promotes survival during gram-positive bacterial
      infection. IL-17A is a critical cytokine that is essential for clearance of
      Streptococcus pneumoniae. However, the mechanism by which ATF3 induces IL-17A
      production remains unknown. Here, we show that ATF3 induces IL-17A production via
      NLRP3 inflammasome-dependent IL-1beta secretion. Survival rates were comparable
      in IL-17A-depleted and ATF3 KO mice but were lower than in WT mice treated with
      isotype control, indicating that ATF3 positively regulated IL-17A production.
      Indeed, ATF3 KO mice showed a marked reduction in IL-17A protein and mRNA
      expression compared to levels in WT mice. Moreover, mitochondrial IL-1beta
      production by bone marrow-derived macrophages was significantly reduced in ATF3
      KO mice as a result of the disruption of cellular ROS and Ca2+ homeostasis.
      Accordingly, ATF3 KO mice displayed diminished survival and bacterial clearance
      following S. pneumoniae infection. Taken together, these data suggest a mechanism
      in which macrophage ATF3 promotes IL-17A production in gammadelta T cells to
      rapidly induce host defenses during early S. pneumoniae infection.

PMID- 30214445
TI  - PD1-CD28 Fusion Protein Enables CD4+ T Cell Help for Adoptive T Cell Therapy in
      Models of Pancreatic Cancer and Non-hodgkin Lymphoma.
AB  - Background: Interaction of the programmed death receptor 1 (PD-1) and its ligand,
      PD-L1, suppresses T cell activity and permits tumors to evade T cell-mediated
      immune surveillance. We have recently demonstrated that antigen-specific CD8+ T
      cells transduced with a PD1-CD28 fusion protein are protected from PD-1-mediated
      inhibition. We have now investigated the potential of PD1-CD28 fusion protein
      transduced CD4+ T cells alone or in combination with CD8+ T cells for
      immunotherapy of pancreatic cancer and non-Hodgkin lymphoma. Methods: OVA
      specific CD4+ and CD8+ were retrovirally transduced with the PD1-CD28 fusion
      protein. Cytokine release, proliferation, cytotoxic activity, and phenotype of
      transduced T cells were assessed in the context of Panc02-OVA (murine pancreatic
      cancer model) and E.G7-PD-L1 (murine T cell lymphoma model) cells. Results:
      Stimulation of PD1-CD28 fusion protein-transduced CD4+ T cells with anti-CD3 and
      recombinant PD-L1 induced specific T cell activation, as measured by IFN-y
      release and T cell proliferation. Coculture with Panc02-OVA or E.G7-PD-L1 tumor
      cells also led to specific activation of CD4+ T cells. Cytokine release and T
      cell proliferation was most effective when tumor cells simultaneously encountered
      genetically engineered CD4+ and CD8+ T cells. Synergy between both cell
      populations was also observed for specific tumor cell lysis. T cell cytotoxicity
      was mediated via granzyme B release and mediated enhanced tumor control in vivo.
      Transduced CD4+ and CD8+ T cells in co-culture with tumor cells developed a
      predominant central memory phenotype over time. Different ratios of CD4+ and CD8+
      transduced T cells led to a significant increase of IFN-y and IL-2 secretion
      positively correlating with CD4+ T cell numbers used. Mechanistically, IL-2 and
      MHC-I were central to the synergistic activity of CD4+ and CD8+ T cells, since
      neutralization of IL-2 prevented the crosstalk between these cell populations.
      Conclusion: PD1-CD28 fusion protein-transduced CD4+ T cells significantly
      improved anti-tumoral effect of fusion protein-transduced CD8+ T cells. Thus, our
      results indicate that PD1-CD28 fusion protein-transduced CD4+ T cells have the
      potential to overcome the PD-1-PD-L1 immunosuppressive axis in pancreatic cancer
      and non-Hodgkin lymphoma.

PMID- 30214442
TI  - Holding All the CARDs: How MALT1 Controls CARMA/CARD-Dependent Signaling.
AB  - The scaffold proteins CARMA1-3 (encoded by the genes CARD11, -14 and -10) and
      CARD9 play major roles in signaling downstream of receptors with immunoreceptor
      tyrosine activation motifs (ITAMs), G-protein coupled receptors (GPCR) and
      receptor tyrosine kinases (RTK). These receptors trigger the formation of
      oligomeric CARMA/CARD-BCL10-MALT1 (CBM) complexes via kinases of the PKC family.
      The CBM in turn regulates gene expression by the activation of NF-kappaB and AP-1
      transcription factors and controls transcript stability. The paracaspase MALT1 is
      the only CBM component having an enzymatic (proteolytic) activity and has
      therefore recently gained attention as a potential drug target. Here we review
      recent advances in the understanding of the molecular function of the protease
      MALT1 and summarize how MALT1 scaffold and protease function contribute to the
      transmission of CBM signals. Finally, we will highlight how dysregulation of
      MALT1 function can cause pathologies such as immunodeficiency, autoimmunity,
      psoriasis, and cancer.

PMID- 30214446
TI  - TCR Analyses of Two Vast and Shared Melanoma Antigen-Specific T Cell Repertoires:
      Common and Specific Features.
AB  - Among Immunotherapeutic approaches for cancer treatment, the adoptive transfer of
      antigen specific T cells is still a relevant approach, that could have higher
      efficacy when further combined with immune check-point blockade. A high number of
      adoptive transfer trials have been performed in metastatic melanoma, due to its
      high immunogenic potential, either with polyclonal TIL or antigen-specific
      polyclonal populations. In this setting, the extensive characterization of T cell
      functions and receptor diversity of infused polyclonal T cells is required,
      notably for monitoring purposes. We developed a clinical grade procedure for the
      selection and amplification of polyclonal CD8 T cells, specific for two shared
      and widely expressed melanoma antigens: Melan-A and MELOE-1. This procedure is
      currently used in a clinical trial for HLA-A2 metastatic melanoma patients. In
      this study, we characterized the T-cell diversity (T-cell repertoire) of such T
      cell populations using a new RNAseq strategy. We first assessed the added-value
      of TCR receptor sequencing, in terms of sensitivity and specificity, by direct
      comparison with cytometry analysis of the T cell populations labeled with anti
      Vbeta-specific antibodies. Results from these analyzes also confirmed specific
      features already reported for Melan-A and MELOE-1 specific T cell repertoires in
      terms of V-alpha recurrence usage, on a very high number of T cell clonotypes.
      Furthermore, these analyses also revealed undescribed features, such as the
      recurrence of a specific motif in the CDR3alpha region for MELOE-1 specific T
      cell repertoire. Finally, the analysis of a large number of T cell clonotypes
      originating from various patients revealed the existence of public CDR3alpha and
      beta clonotypes for Melan-A and MELOE-1 specific T cells. In conclusion, this
      method of high throughput TCR sequencing is a reliable and powerful approach to
      deeply characterize polyclonal T cell repertoires, and to reveal specific
      features of a given TCR repertoire, that would be useful for immune follow-up of
      cancer patients treated by immunotherapeutic approaches.

PMID- 30214447
TI  - Editorial: Cellular Therapies: Past, Present and Future.

PMID- 30214448
TI  - Suppressor of Cytokine Signaling-1/STAT1 Regulates Renal Inflammation in
      Mesangial Proliferative Glomerulonephritis Models.
AB  - Mesangial proliferative glomerulonephritis (MsGN) is a significant global threat
      to public health. Inflammation plays a crucial role in MsGN; however, the
      underlying mechanism remains unknown. Herein, we demonstrate that suppression of
      the cytokine signaling-1 (SOCS1)/signal transducer and activator of transcription
      1 (STAT1) signaling pathway is associated with renal inflammation and renal
      injury in MsGN. Using MsGN rat (Thy1.1 GN) and mouse (Habu GN) models, renal
      SOCS1/STAT1 was determined to be associated with CD4+ T cell infiltration and
      related cytokines. In vitro, SOCS1 overexpression repressed IFN-gamma-induced MHC
      class II and cytokine levels and STAT1 phosphorylation in mesangial cells. SOCS1
      and STAT1 inhibitors significantly inhibited IFN-gamma-induced CIITA promoter
      activity and MHC class II expression. In conclusion, our study emphasizes the
      pivotal role of the SOCS1/STAT1 axis in the regulation of inflammation in MsGN.

PMID- 30214449
TI  - Regulation of Interleukin-6 Receptor Signaling by TNF Receptor-Associated Factor
      2 and 5 During Differentiation of Inflammatory CD4+ T Cells.
AB  - There is growing evidence that tumor necrosis factor (TNF) receptor-associated
      factors (TRAFs) bind to unconventional membrane-bound receptors in many cell
      types and control their key signaling activity, in both positive and negative
      ways. TRAFs function in a variety of biological processes in health and disease,
      and dysregulation of TRAF expression or activity often leads to a patho
      physiological outcome. We have identified a novel attribute of TRAF2 and TRAF5 in
      interleukin-6 (IL-6) receptor signaling in CD4+ T cells. TRAF2 and TRAF5 are
      highly expressed by naive CD4+ T cells and constitutively bind to the signal
      transducing receptor common chain gp130 via the C-terminal TRAF domain. The
      binding between TRAF and gp130 limits the early signaling activity of the IL-6
      receptor complex by preventing proximal interaction of Janus kinases (JAKs)
      associated with gp130. In this reason, TRAF2 and TRAF5 in naive CD4+ T cells
      negatively regulate IL-6-mediated activation of signal transducer and activator
      of transcription 3 (STAT3) that is required for the development of IL-17
      secreting CD4+ TH17 cells. Indeed, Traf2-knockdown in differentiating Traf5-/-
      CD4+ T cells strongly promotes TH17 development. Traf5-/- donor CD4+ T cells
      exacerbate the development of neuroinflammation in experimental autoimmune
      encephalomyelitis (EAE) in wild-type recipient mice. In this review, we summarize
      the current understanding of the role for TRAF2 and TRAF5 in the regulation of IL
      6-driven differentiation of pro-inflammatory CD4+ T cells, especially focusing on
      the molecular mechanism by which TRAF2 and TRAF5 inhibit the JAK-STAT pathway
      that is initiated in the IL-6 receptor signaling complex.

PMID- 30214450
TI  - Structure of TRAF Family: Current Understanding of Receptor Recognition.
AB  - Tumor necrosis factor receptor-associated factor (TRAF) proteins are key
      signaling molecules that function in various cellular signaling events including
      immune response, cell death and survival, development, and thrombosis. Their
      roles in cellular signaling are mediated mostly by direct interactions with
      various receptors via the TRAF domain. To determine how specific TRAF domains can
      interact with various receptors with a limited binding interface and how similar
      binding interfaces of TRAF family members can recognize their specific binding
      partners, extensive structural studies on TRAF family proteins have been
      conducted for several decades. In this review, we discuss the current
      understanding of the structural and molecular diversity of the TRAF domain and
      TRAF-binding motifs in many receptors according to available structural
      information.

PMID- 30214451
TI  - Canola Responses to Drought, Heat, and Combined Stress: Shared and Specific
      Effects on Carbon Assimilation, Seed Yield, and Oil Composition.
AB  - Photosynthetic assimilation is remarkably altered by heat and drought, and this
      depends on the individual or combined occurrence of stressors and their
      respective intensities and durations. Abiotic stressors may also alter the
      nutritional quality and economic value of crops. In this controlled greenhouse
      study, we evaluated the response of Brassica napus L., from flowering to seed
      development, to two temperature and water treatments and a combination of these
      treatments. The diffusional limitations of stomatal conductance and mesophyll
      conductance on photosynthesis, as well as resource-use efficiency (particularly
      water and nitrogen), were assessed. In addition, the effects of stressors on the
      seed fatty acid content and composition and the total protein content were
      examined. The results showed that the reduction in the net photosynthetic
      assimilation rate was caused by combinations of heat and drought (heat + drought)
      treatments, by drought alone, and, to a lesser extent, by heat alone. The
      stomatal conductance decreased under drought and heat + drought treatments but
      not under heat. Conversely, the mesophyll conductance was reduced significantly
      in the plants exposed to heat and heat + drought but not in the plants exposed to
      drought alone. The carboxylation efficiency rate and the electron transport rate
      were reduced under the heat treatment. The seed yield was reduced by 85.3% under
      the heat treatment and, to a lesser extent, under the drought treatment (31%).
      This emphasizes the devastating effects of hotter weather on seed formation and
      development. Seed oil content decreased by 52% in the plants exposed to heat, the
      protein content increased under all the stress treatments. Heat treatment had a
      more deleterious effect than drought on the seed oil composition, leading to
      enhanced levels of saturated fatty oils and, consequently, desaturation
      efficiency, a measure of oil frying ability. Overall, this study showed that
      except for the photosynthetic assimilation rate and stomatal conductance, heat,
      rather than drought, negatively affected the photosynthetic capacity, yield, and
      oil quality attributes when imposed during the flowering and silique-filling
      stages. This result highlights the necessity for a better understanding of heat
      tolerance mechanisms in crops to help to create germplasms that are adapted to
      rapid climate warming.

PMID- 30214452
TI  - Fast Responses of Root Dynamics to Increased Snow Deposition and Summer Air
      Temperature in an Arctic Wetland.
AB  - In wet tundra ecosystems, covering vast areas of the Arctic, the belowground
      plant biomass exceeds the aboveground, making root dynamics a crucial component
      of the nutrient cycling and the carbon (C) budget of the Arctic. In response to
      the projected climatic scenarios for the Arctic, namely increased temperature and
      changes in precipitation patterns, root dynamics may be altered leading to
      significant changes in the net ecosystem C budget. Here, we quantify the single
      and combined effects of 1 year of increased winter snow deposition by snow fences
      and summer warming by open-top chambers (OTCs) on root dynamics in a wetland at
      Disko Island (West Greenland). Based on ingrowth bags, snow accumulation
      decreased root productivity by 42% in the 0-15 cm soil depth compared to ambient
      conditions. Over the growing season 2014, minirhizotron observations showed that
      root growth continued until mid-September in all treatments, and it peaked
      between the end of July and mid-August. During the season, plots exposed to
      experimental warming showed a significant increase in root number during
      September (between 39 and 53%) and a 39% increase in root length by the beginning
      of September. In addition, a significant reduction of root diameter (14%) was
      observed in plots with increased snow accumulation. Along the soil profile (0-40
      cm) summer warming by OTCs significantly increased the total root length (54%),
      root number (41%) and the root growth in the 20-30 cm soil depth (71%). These
      results indicate a fast response of this ecosystem to changes in air temperature
      and precipitation. Hence, on a short-term, summer warming may lead to increased
      root depth and belowground C allocation, whereas increased winter snow
      precipitation may reduce root production or favor specific plant species by means
      of reduced growing season length or increased nutrient cycling. Knowledge on
      belowground root dynamics is therefore critical to improve the estimation of the
      C balance of the Arctic.

PMID- 30214453
TI  - Absolute Quantification of Major Photosynthetic Protein Complexes in
      Chlamydomonas reinhardtii Using Quantification Concatamers (QconCATs).
AB  - For modeling approaches in systems biology, knowledge of the absolute abundances
      of cellular proteins is essential. One way to gain this knowledge is the use of
      quantification concatamers (QconCATs), which are synthetic proteins consisting of
      proteotypic peptides derived from the target proteins to be quantified. The
      QconCAT protein is labeled with a heavy isotope upon expression in E. coli and
      known amounts of the purified protein are spiked into a whole cell protein
      extract. Upon tryptic digestion, labeled and unlabeled peptides are released from
      the QconCAT protein and the native proteins, respectively, and both are
      quantified by LC-MS/MS. The labeled Q-peptides then serve as standards for
      determining the absolute quantity of the native peptides/proteins. Here, we have
      applied the QconCAT approach to Chlamydomonas reinhardtii for the absolute
      quantification of the major proteins and protein complexes driving photosynthetic
      light reactions in the thylakoid membranes and carbon fixation in the pyrenoid.
      We found that with 25.2 attomol/cell the Rubisco large subunit makes up 6.6% of
      all proteins in a Chlamydomonas cell and with this exceeds the amount of the
      small subunit by a factor of 1.56. EPYC1, which links Rubisco to form the
      pyrenoid, is eight times less abundant than RBCS, and Rubisco activase is 32
      times less abundant than RBCS. With 5.2 attomol/cell, photosystem II is the most
      abundant complex involved in the photosynthetic light reactions, followed by
      plastocyanin, photosystem I and the cytochrome b6/f complex, which range between
      2.9 and 3.5 attomol/cell. The least abundant complex is the ATP synthase with 2
      attomol/cell. While applying the QconCAT approach, we have been able to identify
      many potential pitfalls associated with this technique. We analyze and discuss
      these pitfalls in detail and provide an optimized workflow for future
      applications of this technique.

PMID- 30214454
TI  - Activation of Nucleases, PCD, and Mobilization of Reserves in the Araucaria
      angustifolia Megagametophyte During Germination.
AB  - The megagametophyte of mature seeds of Araucaria angustifolia consists of cells
      with thin walls, one or more nuclei, a central vacuole storing proteins, and a
      cytoplasm rich in amyloplasts, mitochondria and lipid bodies. In this study, we
      describe the process of mobilization of reserves and analyzed the dismantling of
      the tissue during germination, using a range of well-established markers of
      programmed cell death (PCD), including: morphological changes in nuclei and
      amyloplasts, DNA degradation, and changes in nuclease profiles. TUNEL reaction
      and DNA electrophoresis demonstrate that DNA fragmentation in nuclei occurs at
      early stages of germination, which correlates with induction of specific
      nucleases. The results of the present study add knowledge on the dismantling of
      the megagametophyte of genus Araucaria, a storage tissue that stores starch as
      the main reserve substance, as well as on the PCD pathway, by revealing new
      insights into the role of nucleases and the expression patterns of putative
      nuclease genes during germination.

PMID- 30214455
TI  - Identification and Analysis of Blood Gene Expression Signature for Osteoarthritis
      With Advanced Feature Selection Methods.
AB  - Osteoarthritis (OA) is a complex disease that affects articular joints and may
      cause disability. The incidence of OA is extremely high. Most elderly people have
      the symptoms of osteoarthritis. The physiotherapy of OA is time consuming, and
      the chances of full recovery from OA are very minimal. The most effective way of
      fighting OA is early diagnosis and early intervention. Liquid biopsy has become a
      popular noninvasive test. To find the blood gene expression signature for OA, we
      reanalyzed the publicly available blood gene expression profiles of 106 patients
      with OA and 33 control samples using an automatic computational pipeline based on
      advanced feature selection methods. Finally, a compact 23-gene set was
      identified. On the basis of these 23 genes, we constructed a Support Vector
      Machine (SVM) classifier and evaluated it with leave-one-out cross-validation.
      Its sensitivity (Sn), specificity (Sp), accuracy (ACC), and Mathew's correlation
      coefficient (MCC) were 0.991, 0.909, 0.971, and 0.920, respectively. Obviously,
      the performance needed to be validated in an independent large dataset, but the
      in-depth biological analysis of the 23 biomarkers showed great promise and
      suggested that mRNA surveillance pathway and multicellular organism growth played
      important roles in OA. Our results shed light on OA diagnosis through liquid
      biopsy.

PMID- 30214457
TI  - 4-Phenyl-1,3-thiazole-2-amines as scaffolds for new antileishmanial agents.
AB  - Background: There is still a need for new alternatives in pharmacological therapy
      for neglected diseases, as the drugs available show high toxicity and parenteral
      administration. That is the case for the treatment of leishmaniasis, particularly
      to the cutaneous clinical form of the disease. In this study, we present the
      synthesis and biological screening of eight 4-phenyl-1,3-thiazol-2-amines assayed
      against Leishmania amazonensis. Herein we propose that these compounds are good
      starting points for the search of new antileishmanial drugs by demonstrating some
      of the structural aspects which could interfere with the observed activity, as
      well as suggesting potential macromolecular targets. Methods: The compounds were
      easily synthesized by the methodology of Hantzsch and Weber, had their purities
      determined by Gas Chromatography-Mass spectrometry and assayed against the
      promastigote forms of Leishmania amazonensis as well as against two white cell
      lines (L929 and THP-1) and the monkey's kidney Vero cells. PrestoBlue(r) and MTT
      viability assays were the methodologies applied to measure the antileishmanial
      and cytotoxic activities, respectively. A molecular modeling target fishing study
      was performed aiming to propose potential macromolecular targets which could
      explain the observed biological behavior. Results: Four out of the eight
      compounds tested exhibited important anti-promastigote activity associated with
      good selectivity indexes when considering Vero cells. For the most promising
      compound, compound 6, IC50 against promastigotes was 20.78 while SI was 5.69.
      Compounds 3 (IC50: 46.63 MUM; SI: 26.11) and 4 (IC50: 53.12 MUM; SI: 4.80) also
      presented important biological behavior. A target fishing study suggested that S
      methyl-5-thioadenosine phosphorylase is a potential target to these compounds,
      which could be explored to enhance activity and decrease the potential toxic side
      effects. Conclusions: This study shows that 4-phenyl-1,3-thiazol-2-amines could
      be good scaffolds to the development of new antileishmanial agents. The S-methyl
      5-thioadenosine phosphorylase could be one of the macromolecular targets involved
      in the action.

PMID- 30214458
TI  - Perioperative care of congenital adrenal hyperplasia - a disparity of physician
      practices in Canada.
AB  - Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency
      is the most common cause of primary adrenal insufficiency in children. Current
      guidelines recommend the use of perioperative stress dose (supraphysiologic)
      glucocorticoids for children with CAH undergoing anesthesia, although a perceived
      difference in practice patterns among Canadian pediatric subspecialists prompted
      an assessment of perioperative glucocorticoid administration. Methods: We
      performed a cross-sectional survey of Canadian Pediatric Anesthesia Society
      (CPAS) and Canadian Pediatric Endocrine Group (CPEG) members via membership email
      lists to assess reported practice patterns to select clinical scenarios. Results:
      Responses were collected from 49 anesthesiologists and 37 pediatric
      endocrinologists. Less than half of anesthesiologists reported they would provide
      stress dose corticosteroids for patients undergoing cystoscopy while a
      significant majority of pediatric endocrinologists reported they would recommend
      stress dose corticosteroid administration (45% vs 92% respectively, p < 0.0001).
      Twenty-one percent of anesthesiologists reported they would not provide stress
      dose corticosteroids for patients undergoing laparotomy. Pediatric
      endocrinologists reported they were more likely to refer to guidelines for
      management of stress dose steroids (84% vs 51%, p < 0.001), with many Canadian
      pediatric endocrinologists reporting to use institution specific guidelines.
      Conclusions: Our results demonstrate a clear difference in the reported approach
      to perioperative stress dose steroids between pediatric anesthesiologists and
      pediatric endocrinologists which may impact patient care. Further dialogue is
      required to address this apparent discrepancy in practice patterns and future
      research is needed to provide evidence-based practice recommendations.

PMID- 30214456
TI  - Stable Histone Methylation Changes at Proteoglycan Network Genes Following
      Ethanol Exposure.
AB  - Alcohol use disorder (AUD) is a chronic mental illness in which patients often
      achieve protracted periods of abstinence prior to relapse. Epigenetic mechanisms
      may provide an explanation for the persisting gene expression changes that can be
      observed even after long periods of abstinence and may contribute to relapse. In
      this study, we examined two histone modifications, histone 3 lysine 4 tri
      methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3), in the
      prefrontal cortex of Withdrawal Seizure Resistant (WSR) mice 21 days after 72 h
      of ethanol vapor exposure. These histone modifications were selected because they
      are associated with active promoters (H3K4me3) and repressed gene expression in a
      euchromatic environment (H3K27me3). We performed a genome-wide analysis to
      identify differences in H3K4me3 and H3K27me3 levels in post-ethanol exposure vs.
      control mice by ChIP-seq. We detected a global reduction in H3K4me3 peaks and
      increase in H3K27me3 peaks in post-ethanol exposure mice compared to controls,
      these changes are consistent with persistent reductions in gene expression.
      Pathway analysis of genes displaying changes in H3K4me3 and H3K27me3 revealed
      enrichment for genes involved in proteoglycan and calcium signaling pathways,
      respectively. Microarray analysis of 7,683 genes and qPCR analysis identified
      eight genes displaying concordant regulation of gene expression and
      H3K4me3/H3K27me3. We also compared changes in H3K4me3 and/or H3K27me3 from our
      study with changes in gene expression in response to ethanol from published
      literature and we found that the expression of 52% of the genes with altered
      H3K4me3 binding and 40% of genes with H3K27me3 differences are altered by ethanol
      exposure. The chromatin changes associated with the 21-day post-exposure period
      suggest that this period is a unique state in the addiction cycle that differs
      from ethanol intoxication and acute withdrawal. These results provide insights
      into the enduring effects of ethanol on proteoglycan and calcium signaling genes
      in the brain.

PMID- 30214459
TI  - A multi-stakeholder perspective on asthma care in Canada: findings from a mixed
      methods needs assessment in the treatment and management of asthma in adults.
AB  - Background: Although several aspects of asthma care have been identified as being
      sub-optimal in Canada, such as patient education, practice guideline adoption,
      and access to care, there remains a need to determine the extent to which these
      gaps remain, so as to investigate their underlying causes, and potential
      solutions. Methods: An ethics-approved mixed methods educational needs assessment
      was conducted in four Canadian provinces (Alberta, British Columbia, Ontario, and
      Quebec), combining a qualitative phase (45-min semi-structured interviews with
      community-based healthcare providers and key stakeholders) and a quantitative
      phase (15-min survey, healthcare providers only). Results: A total of 234
      participants were included in the study, 44 in semi-structured interviews and 190
      in the online survey. Five clinical areas were reported to be suboptimal by
      multiple categories of participants, and specific causes were identified for
      each. These areas included: Integration of guidelines into clinical practice, use
      of spirometry, individualisation of asthma devices to patient needs, emphasis on
      patient adherence and self-management, and clarity regarding roles and
      responsibilities of different members of the asthma healthcare team. Common
      causes for gaps in all these areas included suboptimal knowledge amongst
      healthcare providers, differing perceptions on the importance of certain
      interventions, and inadequate communication between healthcare providers.
      Conclusions: This study provides a better understanding of the specific causes
      underlying common gaps and challenges in asthma care in Canada. This information
      can inform future continuing medical education, and help providers in community
      settings obtain access to adequate materials, resources, and training to support
      optimal care of adult patients with asthma.

PMID- 30214460
TI  - Growth Hormone Did Not Activate Its Intracellular Signaling Molecules in Rats'
      Liver Hepatocytes During Early Life Period.
AB  - Background: Although growth hormone (GH) has essential roles in the growth of
      animals, it has no growth-promoting effect during infancy period. The molecular
      mechanism underlying lack of growth-promoting effect of GH during infancy period
      remains unclear. Important signaling pathways are mediated by GH, including Janus
      kinase 2 (JAK2), extracellular signal-regulated kinase 1/2 (ERK1/2), signal
      transducers, and activators of transcription 5, 3, and 1 (STATs 5, 3 and 1).
      Objectives: This study explored the underlying molecular mechanisms driving to
      the lack of growth-promoting effect of GH in the early stage of life by in vivo
      assessment of intracellular signal response (STAT5/ 3/ 1, JAK2 and ERK1/ 2) to GH
      at different physiological stages. Methods: In this study, five age groups of
      rats (1-, 4-day-old, and 1-, 2-, 3-week-old) were selected. The rats were
      anesthetized using pentobarbital (100 mg/kg) and then received the rat GH
      (2mg/kg) via inferior vena cava injection. The control rats were injected with
      normal saline during the same period. The intracellular signal response to GH was
      assessed by Western blot analysis. Results: JAK2 and STAT5 were expressed in 1
      day and 4-day-old newborn rats and their expression levels were comparable with
      the levels of the 1-, 2-, and 3-week-old rats; however, JAK2/STAT5
      phosphorylation was not observed in 1-day-old and 4-day-old newborn rats after
      stimulation with GH in the liver. Similar to JAK2 and STAT5, we did not detect
      STAT3/1 activation during infancy stages although basic STAT3 and STAT1 were also
      expressed in hepatocytes from newborn rats. In addition we detected ERK1/2
      activation in 4-day-old, 1-, 2-, and 3-week-old rats but not in 1-day-old rats.
      Conclusions: JAK2, STAT5, STAT3, STAT1, and ERK1/2 were not simultaneously
      activated by GH in newborn rats; this finding may be one of the underlying
      mechanism of GH insensitivity in newborn rats.

PMID- 30214461
TI  - Fluconazole as a Safe and Effective Alternative to Ketoconazole in Controlling
      Hypercortisolism of Recurrent Cushing's Disease: A Case Report.
AB  - Introduction: Ketoconazole has long been the first-line medical therapy for
      controlling hypercortisolism secondary to either pituitary or adrenal pathology.
      However, it is largely unavailable in most countries. As a result, we have turned
      to fluconazole as a viable alternative in view of its favourable safety profile.
      Case Presentation: A 50-year-old lady developed recurrent Cushing's disease after
      being in remission following transsphenoidal surgery (TSS) for a left pituitary
      microadenoma 16 years ago. The repeat MRI showed a right pituitary microadenoma
      (1.7 mm * 1.3 mm) for which she underwent a second TSS. However, she continued to
      have persistent hypercortisolism despite repeated MRIs showing absence of tumour
      recurrence. She refused bilateral adrenalectomy and external radiotherapy.
      Ketoconazole was commenced at 200 mg twice daily for disease control but this was
      hindered by intolerable side effects including pruritus and skin exfoliation. In
      the meantime, she suffered a right hypertensive basal ganglia hemorrhage.
      Treatment was subsequently switched to cabergoline and the dose titrated to 0.5
      mg daily. Fluconazole 400 mg daily was later added to control the persistent
      disease. Her clinical and biochemical parameters improved markedly three months
      after the addition of fluconazole. No adverse event was reported. Her disease has
      remained stable for the last 15 months up until the time of the recent clinic
      review. Conclusions: This case demonstrates the long-term efficacy of fluconazole
      in tandem with cabergoline for the control of recurrent Cushing's disease.

PMID- 30214462
TI  - An Overview of Celiac Disease in Childhood Type 1 Diabetes.
AB  - Context: Celiac disease (CD) is a common phenomenon in children with Type 1
      diabetes (T1D). In the present review, we have discussed the pathogenesis,
      diagnostic biomarkers, risk factors, and prognosis of CD in the context of
      pediatric T1D. Evidence Acquisition: Literature published in Web of Science,
      PubMed, Scopus, Google Scholar, and Cochrane Library were scrutinized up to the
      end of 2017. The keywords of celiac disease, Type 1 diabetes, children, and
      pediatric were used in different combinations. Results: Immune cytotoxic
      reactions along with dampen immune regulatory functions contribute to CD in the
      context of pediatric T1D. Many children with simultaneous CD and T1D do not
      represent with the clinical signs of the enteropathy rendering a diagnostic
      challenge. The most common screening tests in these children are routine
      serological tests of CD, anti - endomysial, anti - transglutaminase, and anti -
      deamidated gliadin peptide antibodies. Typing for human leukocyte antigens of DQ 
      2 and DQ - 8 may assist in the diagnosis of silent CD in children with T1D. The
      most significant shared non - HLA genetic loci of CD and T1D comprise CTLA - 4,
      TAGAP, IL - 18RAP, PTPN2, RGS1, SH2B3, CCR5. Interactions between these loci can
      be important in susceptibility to CD in T1D. Some new biomarkers have been
      suggested for diagnosis of CD including ischemia-modified albumin (IMA), soluble
      syndecan-1 (SSDC-1), regenerating gene Ialpha (REG-Ialpha), Neurotensin, and
      Zonulin, which can be useful for diagnosis and screening of CD in childhood T1D.
      Conclusions: Overall, active seropositive CD seems to be of clinical importance
      in T1D with significant impacts on the quality of life and predisposition to
      diabetes associated complications. It is important to detect CD in the context of
      T1D to prevent potential risks contributing to morbidities and mortalities
      associated with either CD or T1D.

PMID- 30214463
TI  - Spectral Doppler and automated software-guided ultrasound assessment of bilateral
      common carotid intima-media thickness in spondyloarthritis: is there a
      correlation with clinical findings?
AB  - Background and aim: Limited information is currently available about whether
      carotid intima-media thickness (IMT) correlates with the degree of disease
      activity in spondyloarthritis. The objective of this study was to evaluate the
      correlation between articular and carotid ultrasound data and laboratory and
      clinical variables in patients with spondyloarthritis. Methods: Twenty-two
      patients with spondyloarthritis, recruited consecutively via the
      spondyloarthritis service of the Universidade Pontificia Catolica de Campinas,
      Sao Paulo, Brazil, were assessed using carotid artery ultrasound (radiofrequency
      quality intima-media thickness, RF-QIMT), joint ultrasound, clinical evaluation,
      and laboratory tests. Results: Mean (standard deviation, SD) carotid RF-QIMT was
      0.643 (0.16) mm. Mean (SD) resistive index (RI) values for the right and left
      carotid arteries were 0.67 (0.12) and 0.82 (0.38), respectively. Mean (SD) RI
      values for the right and left sacroiliac joints were 1.10 (0.97) and 0.94 (0.13),
      respectively. Several significant correlations were detected between ultrasound,
      clinical, and laboratory variables. Notably, there were correlations between
      sacroiliac RI and erythrocyte sedimentation rate (p=0.027) and RF-QIMT (p=0.037);
      between RF-QIMT and Framingham score (p=0.012) and metabolic parameters,
      including abdominal waist measurement, body mass index (BMI) (p=0.032 to
      p=0.044). Conclusions: In patients with spondyloarthritis, RF-QIMT detected
      atherosclerotic changes in the carotid artery wall, and spectral Doppler detected
      inflammatory activity in sacroiliac joints. Positive correlations were observed
      between these ultrasound findings and parameters reflecting patients' metabolic
      profile and alterations in inflammatory markers.

PMID- 30214467
TI  - A multiplexed gas exchange system for increased throughput of photosynthetic
      capacity measurements.
AB  - Background: Existing methods for directly measuring photosynthetic capacity
      (Amax) have low throughput, which creates a key bottleneck for pre-breeding and
      ecological research. Currently available commercial leaf gas exchange systems are
      not designed to maximize throughput, on either a cost or time basis. Results: We
      present a novel multiplexed semi-portable gas exchange system, OCTOflux, that can
      measure Amax with approximately 4-7 times the throughput of commercial devices,
      despite a lower capital cost. The main time efficiency arises from having eight
      leaves simultaneously acclimate to saturating CO2 and high light levels; the long
      acclimation periods for each leaf (13.8 min on average in this study) thus
      overlap to a large degree, rather than occurring sequentially. The cost
      efficiency arises partly from custom-building the system and thus avoiding
      commercial costs like distribution, marketing and profit, and partly from
      optimizing the system's design for Amax throughput rather than flexibility for
      other types of measurements. Conclusion: Throughput for Amax measurements can be
      increased greatly, on both a cost and time basis, by multiplexing gas streams
      from several leaf chambers connected to a single gas analyzer. This can help
      overcome the bottleneck in breeding and ecological research posed by limited
      phenotyping throughput for Amax.

PMID- 30214464
TI  - Primary genetic disorders affecting high density lipoprotein (HDL).
AB  - There is extensive evidence demonstrating that there is a clear inverse
      correlation between plasma high density lipoprotein cholesterol (HDL-C)
      concentration and cardiovascular disease (CVD). On the other hand, there is also
      extensive evidence that HDL functionality plays a very important role in
      atheroprotection. Thus, genetic disorders altering certain enzymes, lipid
      transfer proteins, or specific receptors crucial for the metabolism and adequate
      function of HDL, may positively or negatively affect the HDL-C levels and/or HDL
      functionality and subsequently either provide protection or predispose to
      atherosclerotic disease. This review aims to describe certain genetic disorders
      associated with either low or high plasma HDL-C and discuss their clinical
      features, associated risk for cardiovascular events, and treatment options.

PMID- 30214466
TI  - Using donor human milk to feed vulnerable term infants: a case series in KwaZulu
      Natal, South Africa.
AB  - Background: Donor human milk is the World Health Organization's recommendation
      for infant feeding when the mother's own breast milk is unavailable. Breast milk
      has been shown to reduce morbidity and mortality and in low birthweight infants,
      donor milk reduces the incidence of necrotising enterocolitis, late onset sepsis
      and improves outcomes. There is a paucity of literature documenting outcomes of
      using donor human milk in older children who need additional support for a
      variety of health issues. Case presentation: A series of seven case studies is
      presented of orphaned and abandoned children, many of whom were either HIV
      exposed or positive. All children were fed with pasteurised donor human milk at a
      transition home and their progress reported. Conclusions: Although detailed
      medical records were not always available, the case studies provide anecdotal
      evidence of the protective effects of donor human milk against failure to thrive,
      diarrhoea, atopic dermatitis, and opportunistic infections.

PMID- 30214468
TI  - Development of a seedling inoculation technique for rapid evaluation of soybean
      for resistance to Phomopsis longicolla under controlled conditions.
AB  - Background: Phomopsis seed decay (PSD) of soybean (Glycine max L. Merr.) is
      caused primarily by the seed-borne fungal pathogen Phomopsis longicolla T. W.
      Hobbs. The PSD disease reduces seed quality and yield worldwide. Development of
      effective techniques to evaluate soybean for resistance to PSD can facilitate
      identification of new sources of host resistance to manage the disease. This
      study was undertaken to develop and utilize a rapid cut-seedling inoculation
      technique to evaluate soybean genotypes for resistance to P. longicolla under
      controlled conditions. Results: There were no significant differences in stem
      lesion length determined as the area under disease progress curve at 24  degrees
      C and 30  degrees C. The 21 and 14-day-old seedlings were more susceptible than
      the older seedlings. Inoculation with 7 or 14-day-old pathogens caused higher
      values of AUDPC than older pathogen cultures. Isolates MS17-1 was the most
      aggressive isolate from the test of 25 isolates from seven states in the U.S.
      Eighteen previously reported field PSD-resistant accessions had significantly
      lower AUDPC than the susceptible checks and other entries (P <= 0.05).
      Conclusion: This study provided rapid evaluation of soybeans for reaction to P.
      longicolla and identification of PSD-resistant genotypes. Although PSD is a
      soybean seed disease, results from the cut-seedling inoculation assays without
      waiting a whole growing season were comparable to those obtained from field
      tests. Additionally, concerns about the environmental effects and uneven
      distribution of the pathogen in the field were ameliorated. The cut-seedling
      inoculation technique can also be used to speed up evaluation of PSD populations
      for the discovery of PSD-resistance gene(s), and high throughput phenotyping of
      seed diseases at seedling stage for genetics and genomic studies.

PMID- 30214465
TI  - Amygdala functional connectivity in female patients with major depressive
      disorder with and without suicidal ideation.
AB  - Background: Major depressive disorder (MDD) is a known major risk factor for
      suicide and is one of the most common mental disorders. Meanwhile, gender
      differences in suicidal behavior have long been recognized including the finding
      that women have higher rates of suicidal ideation and/or suicidal behavior than
      men. The mechanism underlying suicide ideation in female patients with MDD
      remains poorly understood. The aim of the present study was to examine possible
      suicidal behavior-related neural circuitry in female MDD. Methods: In this study,
      15 female participants with the first-episode MDD with suicidal ideation and 24
      participants with the first-episode MDD without suicidal ideation as well as 39
      female participants in a healthy control (HC) group, ranging in age from 18 to 50
      years, underwent resting-state functional magnetic resonance imaging. The whole
      brain amygdala resting-state functional connectivity (rsFC) was compared among
      these three groups. Results: Compared with female participants with the first
      episode MDD without suicidal ideation and those in the HC group, female
      participants with the first-episode MDD with suicidal ideation showed a
      significant difference in rsFC between the amygdala and precuneus/cuneus (p <
      0.05, corrected). No significant difference in amygdala-precuneus/cuneus rsFC was
      observed between female patients with the first-episode MDD without suicidal
      ideation and the HC group (p < 0.05, corrected). Conclusions: Our findings
      suggest that suicidal ideation in female patients with the first-episode MDD may
      be related to an abnormality in amygdala neural circuitry. The abnormality in
      amygdala-precuneus/cuneus functional connectivity might present the trait feature
      for suicide in women with the first-episode MDD. The precuneus/cuneus may be an
      important region related to suicide and require future study.

PMID- 30214469
TI  - A combination of SOFA score and biomarkers gives a better prediction of septic
      AKI and in-hospital mortality in critically ill surgical patients: a pilot study.
AB  - Background: Sepsis is a syndrome characterized by a constellation of clinical
      manifestations and a significantly high mortality rate in the surgical intensive
      care unit (ICU). It is frequently complicated by acute kidney injury (AKI),
      which, in turn, increases the risk of mortality. Therefore, it is of paramount
      importance to identify those septic patients at risk for the development of AKI
      and mortality. The objective of this pilot study was to evaluate several
      different biomarkers, including NGAL, calprotectin, KIM-1, cystatin C, and GDF
      15, along with SOFA scores, in predicting the development of septic AKI and
      associated in-hospital mortality in critically ill surgical patients. Methods:
      Patients admitted to the surgical ICU were prospectively enrolled, having given
      signed informed consent. Their blood and urine samples were obtained and
      subjected to enzyme-linked immunosorbent assay (ELISA) to determine the levels of
      various novel biomarkers. The clinical data and survival outcome were recorded
      and analyzed. Results: A total of 33 patients were enrolled in the study. Most
      patients received surgery prior to ICU admission, with abdominal surgery being
      the most common type of procedure (27 patients (81.8%)). In the study, 22
      patients had a diagnosis of sepsis with varying degrees of AKI, while the
      remaining 11 were free of sepsis. Statistical analysis demonstrated that in
      patients with septic AKI versus those without, the following were significantly
      higher: serum NGAL (447.5 +/- 35.7 ng/mL vs. 256.5 +/- 31.8 ng/mL, P value
      0.001), calprotectin (1030.3 +/- 298.6 pg/mL vs. 248.1 +/- 210.7 pg/mL, P value
      0.049), urinary NGAL (434.2 +/- 31.5 ng/mL vs. 208.3 +/- 39.5 ng/mL, P value <
      0.001), and SOFA score (11.5 +/- 1.2 vs. 4.4 +/- 0.5, P value < 0.001). On the
      other hand, serum NGAL (428.2 +/- 32.3 ng/mL vs. 300.4 +/- 44.3 ng/mL, P value
      0.029) and urinary NGAL (422.3 +/- 33.7 ng/mL vs. 230.8 +/- 42.2 ng/mL, P value
      0.001), together with SOFA scores (10.6 +/- 1.4 vs. 5.6 +/- 0.8, P value 0.003),
      were statistically higher in cases of in-hospital mortality. A combination of
      serum NGAL, urinary NGAL, and SOFA scores could predict in-hospital mortality
      with an AUROC of 0.911. Conclusions: This pilot study demonstrated a promising
      panel that allows an early diagnosis, high sensitivity, and specificity and a
      prognostic value for septic AKI and in-hospital mortality in surgical ICU.
      Further study is warranted to validate our findings.

PMID- 30214470
TI  - Flexible versus rigid endoscopy in the management of esophageal foreign body
      impaction: systematic review and meta-analysis.
AB  - Background: Foreign body (FB) impaction accounts for 4% of emergency endoscopies
      in clinical practice. Flexible endoscopy (FE) is recommended as the first-line
      therapeutic option because it can be performed under sedation, is cost-effective,
      and is well tolerated. Rigid endoscopy (RE) under general anesthesia is less used
      but may be advantageous in some circumstances. The aim of the study was to
      compare the efficacy and safety of FE and RE in esophageal FB removal. Methods:
      PubMed, MEDLINE, Embase, and Cochrane databases were consulted matching the terms
      "Rigid endoscopy AND Flexible endoscopy AND foreign bod*". Pooled effect measures
      were calculated using an inverse-variance weighted or Mantel-Haenszel in random
      effects meta-analysis. Heterogeneity was evaluated using I2 index and Cochrane Q
      test. Results: Five observational cohort studies, published between 1993 and
      2015, matched the inclusion criteria. One thousand four hundred and two patients
      were included; FE was performed in 736 patients and RE in 666. Overall, 101
      (7.2%) complications occurred. The most frequent complications were mucosal
      erosion (26.7%), mucosal edema (18.8%), and iatrogenic esophageal perforations
      (10.9%). Compared to FE, the estimated RE pooled success OR was 1.00 (95% CI 0.48
      2.06; p = 1.00). The pooled OR of iatrogenic perforation, other complications,
      and overall complications were 2.87 (95% CI 0.96-8.61; p = 0.06), 1.09 (95% CI
      0.38-3.18; p = 0.87), and 1.50 (95% CI 0.53-4.25; p = 0.44), respectively. There
      was no mortality. Conclusions: FE and RE are equally safe and effective for the
      removal of esophageal FB. To provide a tailored or crossover approach, patients
      should be managed in multidisciplinary centers where expertise in RE is also
      available. Formal training and certification in RE should probably be re
      evaluated.

PMID- 30214471
TI  - Characterization and anti-tumor activity of a polysaccharide isolated from
      Dendrobium officinale grown in the Huoshan County.
AB  - Background: Polysaccharides are carbohydrate chains composed of linked
      monosaccharide units. Accumulating studies report that polysaccharides isolated
      from Dendrobium officinale have a variety of functions. However, the composition
      and anti-tumor activity of D. officinale grown in the Huoshan area are largely
      unknown. Methods: A polysaccharide (DOPA-1) was isolated from D. officinale by
      hot water extraction and ethanol precipitation, followed by purification via DEAE
      cellulose and Sephadex G-100 chromatography. DOPA-1 was analyzed by infrared and
      nuclear magnetic resonance and then characterized by periodate oxidation and
      Smith degradation. The anti-tumor activity of DOPA-1 was then tested in HepG-2
      cells. Results: Our results show that DOPA-1 is mainly comprised of mannose,
      glucose, and galactose at a molar ratio of 1:0.42:0.27 and has an average
      molecular weight of 2.29 * 105 Da. Additionally, DOPA-1 inhibited HepG-2 cell
      growth in a dose-dependent manner. DOPA-1-treated HepG-2 cells also had increased
      reactive oxygen species (ROS) levels and decreased mitochondrial membrane
      potential. Furthermore, apoptosis was observed in DOPA-1-treated HepG-2 cells
      along with Bcl-2 downregulation and Bax upregulation at the protein level.
      Conclusions: Our findings suggest that DOPA-1 induces apoptosis in tumor cells
      via altered mitochondrial function, ROS production, and altered apoptosis-related
      protein expression. This bioactive polysaccharide could, therefore, potentially
      be further developed as an anti-tumor adjuvant drug.

PMID- 30214472
TI  - A cross-sectional assessment of diabetes self-management, education and support
      needs of Syrian refugee patients living with diabetes in Bekaa Valley Lebanon.
AB  - Background: Patients with diabetes require knowledge and skills to self-manage
      their disease, a challenging aspect of treatment that is difficult to address in
      humanitarian settings. Due to the lack of literature and experience regarding
      diabetes self-management, education and support (DSMES) in refugee populations,
      Medecins Sans Frontieres (MSF) undertook a DSMES survey in a cohort of diabetes
      patients seen in their primary health care program in Lebanon. Methods:
      Structured interviews were conducted with diabetes patients in three primary care
      clinics between January and February 2015. Scores (0-10) were calculated to
      measure diabetes core knowledge in each patient (the DSMES score). Awareness of
      long-term complications and educational preferences were also assessed. Analyses
      were conducted using Stata software, version 14.1 (StataCorp). Simple and
      multiple linear regression models were used to determine associations between
      various patient factors and the DSMES Score. Results: A total of 292 patients
      were surveyed. Of these, 92% had type 2 diabetes and most (70%) had been
      diagnosed prior to the Syrian conflict. The mean DSMES score was 6/10. Having
      secondary education, previous diabetes education, a 'diabetes confidant', and
      insulin use were each associated with a higher DSMES Score. Lower scores were
      significantly more likely to be seen in participants with increasing age and in
      patients who were diagnosed during the Syrian conflict. Long-term complications
      of diabetes most commonly known by patients were vision related complications
      (68% of patients), foot ulcers (39%), and kidney failure (38%). When asked about
      the previous Ramadan, 56% of patients stated that they undertook a full fast,
      including patients with type 1 diabetes. Individual and group lessons were
      preferred by more patients than written, SMS, telephone or internet-based
      educational delivery models. Conclusions: DSMES should be patient and context
      appropriate. The variety and complexities of humanitarian settings provide
      particular challenges to its appropriate provision. Understanding patient
      baseline DSMES levels and needs provides a useful basis for humanitarian
      organizations seeking to provide diabetes care.

PMID- 30214473
TI  - The OB Medicine Discussion listserv.

PMID- 30214474
TI  - Hypermobile Ehlers-Danlos syndrome and pregnancy.
AB  - Ehlers-Danlos syndromes are a clinically and genetically heterogeneous group of
      rare inherited connective tissue disorders. Hypermobile Ehlers-Danlos syndrome is
      one of the common types and not infrequently encountered in pregnancy. While, in
      the majority of women with hypermobile Ehlers-Danlos syndrome, the pregnancy is
      uncomplicated, it is important to be aware of the condition in view of potential
      complications such as recurrent joint dislocations and history of surgical joint
      stabilization procedures, secondary autonomic pain and postural orthostatic
      tachycardia syndrome. Increased awareness of the condition and a multi
      disciplinary approach to the management of these women in pregnancy result in
      good outcome for the mother and the baby. We report the clinical characteristics
      and outcome of pregnancies in eight women with hypermobile Ehlers-Danlos syndrome
      and present a review of the literature with particular reference to management in
      a pregnant woman with joint hypermobility syndrome.

PMID- 30214475
TI  - Fertility and pregnancy in cancer survivors.
AB  - Cancer survivors are increasing as improvements in cancer diagnosis and treatment
      translate to improved outcomes. As cancer survivors in their reproductive years
      contemplate pregnancy, it is important to understand the impact of cancer and its
      treatment on fertility and pregnancy outcomes. Cancer treatments such as
      chemotherapy and radiotherapy can affect patients' fertility, and strategies are
      available to help preserve the future fertility of survivors. The potential
      impact of previous cancer diagnoses and treatments on pregnancy and maternal and
      fetal outcomes needs to be assessed and discussed with survivors, with support
      from materno-fetal medicine specialists and high-risk antenatal services as
      needed.

PMID- 30214476
TI  - The effect of pre-eclampsia on retinal microvascular caliber at delivery and post
      partum.
AB  - Background: The retinal microcirculation provides a unique view of microvessel
      structure by means of non-invasive, retinal image analysis. The aim of the study
      was to compare the retinal vessel caliber at delivery and one-year post-partum
      between women who have had pre-eclampsia during pregnancy to a normotensive
      control group. Methods: Digital photos of the eye were taken at delivery and one
      year post-partum. Retinal vessels were analysed and summarised as the corrected
      central retinal arteriolar equivalent and corrected central retinal venular
      equivalent. Results: The corrected central retinal arteriolar equivalent and
      corrected central retinal venular equivalent were significantly lower in the pre
      eclamptic group compared to the control group both at delivery and one-year post
      partum (p < 0.001). Conclusion: Retinal artery and venular caliber changes that
      occur during pregnancies affected by pre-eclampsia persist for up to one-year
      post-partum. These changes may reflect a permanent, long-term microvascular
      dysfunction and may be useful as a biomarker of future vascular risk.

PMID- 30214477
TI  - Visceral fat mass as a novel risk factor for predicting gestational diabetes in
      obese pregnant women.
AB  - Objective: To develop a model to predict gestational diabetes mellitus
      incorporating classical and a novel risk factor, visceral fat mass. Methods:
      Three hundred two obese non-diabetic pregnant women underwent body composition
      analysis at booking by bioimpedance analysis. Of this cohort, 72 (24%) developed
      gestational diabetes mellitus. Principal component analysis was initially
      performed to identify possible clustering of the gestational diabetes mellitus
      and non-GDM groups. A machine learning algorithm was then applied to develop a
      GDM predictive model utilising random forest and decision tree modelling.
      Results: The predictive model was trained on 227 samples and validated using an
      independent testing subset of 75 samples where the model achieved a validation
      prediction accuracy of 77.53%. According to the decision tree developed, visceral
      fat mass emerged as the most important variable in determining the risk of
      gestational diabetes mellitus. Conclusions: We present a model incorporating
      visceral fat mass, which is a novel risk factor in predicting gestational
      diabetes mellitus in obese pregnant women.

PMID- 30214478
TI  - Physiological changes of pregnancy and the Swansea criteria in diagnosing acute
      fatty liver of pregnancy.
AB  - The Swansea criteria are used to assess the likelihood of acute fatty liver of
      pregnancy. There are significant physiological changes in normal pregnancy in
      several of the pathology parameters used in the Swansea criteria. This may impact
      the sensitivity and specificity of the Swansea criteria. Five of the 11 case
      series reporting laboratory values in acute fatty liver of pregnancy used values
      divergent from the Swansea criteria. When using the Swansea criteria for
      diagnosis of acute fatty liver of pregnancy, using pregnancy-specific and/or
      laboratory-specific reference intervals is recommended. Simpler diagnostic
      criteria using parameters of hepatocellular damage and hepatic synthetic
      dysfunction may be an alternative to the Swansea criteria, and further studies
      investigating the sensitivity and specificity of these parameters would be
      useful.

PMID- 30214479
TI  - Development of a Core Outcome Set for research on critically ill obstetric
      patients: A study protocol.
AB  - Background: Current data on critical illness during pregnancy are insufficient
      for evidence-based decision making. Core outcome sets are promoted to improve
      reporting of outcomes important to decision makers. We aim to develop a Core
      Outcome Set for research on critically ill obstetric patients (COSCO study).
      Methods: We will perform a systematic review of studies on critical illness in
      pregnancy and focus groups or interviews with women who were critically ill while
      being pregnant. These data will inform an international Delphi survey where
      stakeholders will rank proposed outcomes. Selected outcomes will be brought
      forward to a consensus meeting where core outcomes will be defined. We will then
      complete a second consensus process to define measures for each core outcome.
      Conclusion: The Core Outcome Set on Critically ill Obstetric patients study aims
      to develop a set of core outcomes to be part of all studies on critically ill
      obstetric patients. Implementation of this core outcome set will help improve
      future research efforts.Trial registration: This study is registered on the COMET
      initiative website (COS #916). This systematic review is registered on PROSPERO
      (CRD #42017071944).

PMID- 30214480
TI  - Insights into pregnancy associated and atypical hemolytic uremic syndrome.

PMID- 30214481
TI  - Acute fatty liver of pregnancy in a woman with ulcerative colitis and familial
      hidradenitis suppurativa.
AB  - Acute fatty liver of pregnancy is a heterogeneous disorder which may occur in the
      absence of a detectable gene mutation for the enzyme long-chain L-3-hydroxyacyl
      CoA dehydrogenase. Acute fatty liver of pregnancy has been reported to complicate
      several gastrointestinal disorders including viral hepatitis, chronic active
      hepatitis and intrahepatic cholestasis of pregnancy. A case of acute fatty liver
      of pregnancy in a woman with ulcerative colitis and familial hidradenitis
      suppurativa without a detectable gene mutation is presented. The potential role
      of inflammatory cytokines in precipitating acute fatty liver of pregnancy is
      discussed.

PMID- 30214482
TI  - Coronary artery dissection in the puerperium: A case report and literature
      review.
AB  - Spontaneous coronary artery dissection is a rare but important cause of acute
      coronary syndrome. Its relevance for women during the puerperium mandates
      awareness and understanding amongst obstetric healthcare professionals. The
      aetiology of the increased risk in pregnancy has not been fully elucidated, but
      include medial eosinophilic angitis, pregnancy-induced degeneration of collagen
      in conjunction with the stresses of parturition, and rupture of the vasa vasorum.
      The risk of mortality necessitates prompt diagnosis, usually by angiography.
      There is no one-size-fits-all treatment; management must be individualised
      according to haemodynamic status and affected vessel(s) and includes conservative
      management, percutaneous coronary intervention, or bypass grafting. Recovery
      complications include extension of the haematoma or false lumen, valvular
      pathology secondary to ischaemia, and sudden cardiac death. Close post-operative
      surveillance is mandatory. We present a 41-year-old lady with post-partum
      spontaneous coronary artery dissection, complicated by ischaemic papillary
      rupture and mitral regurgitation requiring valve replacement. Additionally, we
      present a literature review, including guidance on management and critical
      analysis of potential complications.

PMID- 30214483
TI  - Wilson's disease presenting during pregnancy: A diagnostic and therapeutic
      dilemma.
AB  - Wilson's disease is an autosomal recessive genetic disorder affecting copper
      transport leading to hepatic and/or neuropsychiatric manifestations. Changes in
      pregnancy can mimic certain clinical features of chronic liver disease such as
      spider naevi, and constraints for the use of various investigation for diagnosis
      pose a challenge to physicians. A high index of suspicion, multi-disciplinary
      team approach, use of correct non-invasive testing including viral serology,
      autoantibodies and copper studies and ultrasonography help to diagnose most of
      the pre-existing, de novo or pregnancy-specific hepatological conditions. We
      report a case of Wilson's disease diagnosed during pregnancy and discuss the
      challenges in diagnosis and treatment in pregnancy.

PMID- 30214485
TI  - Pretreatment of South African sugarcane bagasse using a low-cost protic ionic
      liquid: a comparison of whole, depithed, fibrous and pith bagasse fractions.
AB  - Background: Sugarcane bagasse is an abundant and geographically widespread agro
      industrial residue with high carbohydrate content, making it a strong candidate
      feedstock for the bio-based economy. This study examines the use of the low-cost
      protic ionic liquid triethylammonium hydrogen sulfate ([TEA][HSO4]) to
      fractionate a range of South African sugarcane bagasse preparations into a
      cellulose-rich pulp and lignin. The study seeks to optimize pretreatment
      conditions and examine the necessity of applying a depithing step on bagasse
      prior to pretreatment. Results: Pretreatment of five bagasse preparations, namely
      whole, industrially depithed, laboratory depithed (short and long fiber) and pith
      bagasse with [TEA][HSO4]:[H2O] (4:1 w/w) solutions produced highly digestible
      cellulose-rich pulps, as assessed by residual lignin analysis and enzymatic
      hydrolysis. Pretreatment under the optimized condition of 120  degrees C for 4 h
      produced a pretreated cellulose pulp with up to 90% of the lignin removed and
      enabled the release of up to 69% glucose contained in the bagasse via enzymatic
      hydrolysis. Glucose yields from whole and depithed bagasse preparations were very
      similar. Significant differences in lignin recovery were obtained for laboratory
      depithed bagasse compared with whole and industrially depithed bagasse. The
      silica-rich ash components of bagasse were seen to partition mainly with the
      pulp, from where they could be easily recovered in the post-hydrolysis solids.
      Conclusions: The five bagasse preparations were compared but did not show
      substantial differences in composition or cellulose digestibility after
      pretreatment. Evidence was presented that a depithing step appears to be
      unnecessary prior to ionoSolv fractionation, potentially affording significant
      cost and energy savings. Instead, lignin re-deposition onto the pulp surface
      (and, in turn, particle size and shape) appeared to be major factors affecting
      the conditioning of bagasse with the applied IL. We show that pith bagasse, a
      common by-product of paper making, can be successfully conditioned for high
      glucose release while allowing recovery of lignin and silica-rich ash. The
      glucose yields obtained for bagasse using [TEA][HSO4]-water mixtures were ~ 75%
      as high as for conventional aprotic ionic liquids such as [Emim][OAc]; this
      result is highly promising for commercialization of ionoSolv processing given
      [TEA][HSO4] is 40 times less expensive, thermally stable and recyclable.

PMID- 30214486
TI  - Short-term disability progression in two multiethnic multiple sclerosis centers
      in the treatment era.
AB  - Background: Short-term disease progression is well documented in clinical trials,
      but there are limited published data on disease course in real-life practice.
      Methods: Patient-derived Multiple Sclerosis Severity Score (PMSSS), a disease
      severity rank score, was computed at each visit for consecutive MS patients
      attending two large, ethnically diverse MS centers in New York metropolitan area.
      Disability was assessed via Patient-Determined Disease Steps (PDDS). Clinicians
      recorded disease subtype and relapse status at each visit, but did not rate
      disability. PMSSS change from the first to the last visit was calculated for the
      cohort as a whole and for subgroups of interest. Multivariable regression models
      were constructed for predicting final PMSSS based on readily available predictor
      variables collected at the initial visit and relapse history during follow up.
      Results: A total of 1740 consecutive patients from New York University (n = 1079)
      and Barnabas (n = 661) MS Care Centers were included. During follow up (mean 2.4
      +/- 0.82 years, range 1-4 years), mean PDDS score increased from 1.9 +/- 2.2 to
      2.3 +/- 2.2 (p < 0.0001), while PMSSS remained roughly unchanged (initial PMSSS =
      3.71 +/- 2.73, last PMSSS = 3.81 +/- 2.76, paired t test, p = 0.28). The only
      major predictor of final PMSSS was the initial PMSSS. Demographic variables (age,
      sex, race) or relapse status did not predict final severity score. Conclusions:
      Baseline disability in two MS clinics was much lower than in the reference
      population from which PMSSS was derived. We observed no discernable slowing of
      disability accumulation during the short-term follow up in our cohort compared
      with the reference cohort. Overwhelmingly the most important predictor of final
      disease severity rank score was the initial disease severity rank score.

PMID- 30214484
TI  - Engineering and monitoring cellular barrier models.
AB  - Epithelia and endothelia delineate tissue compartments and control their
      environments by regulating the passage of ions and solutes. This barrier function
      is essential for the development and maintenance of multicellular organisms, and
      its dysfunction is associated with numerous human diseases. Recent advances in
      biomaterials and microfabrication technologies have evolved in vitro approaches
      for modelling biological barriers. Current microphysiological systems have become
      more efficient and reliable in mimicking the cell microenvironment. Additionally,
      methods for the quantification of barrier permeability have long provided
      significant insight into their underlying mechanisms. In this review, we outline
      the current techniques to quantify the barrier function of engineered tissues,
      and we also give an overview of recent microphysiological systems of biological
      barriers that emulate the microenvironment and microarchitecture of native
      tissues.

PMID- 30214487
TI  - Effect of high and low-supportive footwear on female tri-planar knee moments
      during single limb landing.
AB  - Background: Higher landing-related external knee joint moments at later stages of
      female pubertal development likely contribute to a higher incidence of non
      contact anterior cruciate ligament (ACL) injury. Athletic footwear may provide a
      potential strategy to alter higher knee moments. Methods: Thirty-one late/post
      pubertal girls (Tanner stage IV-V, menarche and growth spurt attained) performed
      a single limb drop lateral jump in three footwear conditions (barefoot, low
      support shoes and high support shoes), in which peak knee abduction moment
      (KAbM), flexion moment (KFM) and internal rotation moments (KIRM) were measured.
      Repeated measures ANOVA and ANCOVA were used to test for a main effect of
      footwear with and without foot posture index (FPI) as a covariate (p < 0.05) with
      post-hoc test carried out via Fisher's Least Significant Difference (LSD).
      Results: A main effect of footwear condition was observed for peak KFM (p <
      0.05), but not KAbM or KIRM, in both unadjusted and adjusted models. Post-hoc
      analysis demonstrated that both high- and low-support shoes increased peak KFM
      compared with barefoot (p < 0.001). Conclusion: Our findings indicate
      commercially available high- and low-supportive footwear increase peak KFM, but
      do not effect KAbM or KIRM while landing among late/post-pubertal girls. This
      suggests that these styles of footwear are inadequate at reducing higher knee
      moments in an at-risk cohort.

PMID- 30214489
TI  - An assessment of quality of randomized controlled trials in shoulder instability
      surgery using a modification of the clear CLEAR-NPT score.
AB  - Background: The present study aimed to evaluate the methodological quality and
      determine the quality of reporting of randomized controlled trials (RCTs) that
      assess surgical treatment for shoulder instability. Methods: A Cochrane, Pubmed,
      EMBASE and Trip database search was performed, including the relevant literature,
      regarding RCTs that report on shoulder instability published between January 1994
      and January 2017. Methodological quality was assessed with a modification of the
      Checklist to Evaluate A Report of a Nonpharmacologic Trial (CLEAR-NPT). Points
      were assigned based on 18 items regarding patient characteristics, randomization,
      care provider characteristics, surgical details and blinding, with a total score
      ranging from 0 points to 18 points. Missing items were verified with the
      corresponding authors of the studies. Quality of reporting corresponds to the
      total scores including the items that were additionally provided by the authors.
      Results: We included 22 studies. Of these, nine corresponding authors provided
      additional information. The average methodological quality was 16.9 points (11
      studies) and the average quality of reporting was 9.5 points (22 studies). Items
      scoring worst included information regarding the surgeon's experience, the
      patients' level of activity, comorbidities, analyzing according to 'intention-to
      treat' principles, and blinding of care providers, participants and assessors.
      Conclusions: RCTs reporting on shoulder instability surgery are well performed
      but poorly reported.

PMID- 30214488
TI  - Clinical application of a multiplex genetic pathogen detection system remaps the
      aetiology of diarrhoeal infections in Shanghai.
AB  - Background: Culture-based diagnostic methods cannot achieve rapid and precise
      diagnoses for the identification of multiple diarrhoeal pathogens (DPs). A high
      throughput multiplex genetic detection system (HMGS) was adapted and evaluated
      for the simultaneous identification and differentiation of infectious DPs and a
      broad analysis of DP infection aetiology. Results: DP-HMGS was highly sensitive
      and specific for DP detection compared with culture-based techniques and was
      similar to singleplex real-time PCR. The uniform level of sensitivity of DP-HMGS
      for all DPs allowed us to remap the aetiology of acute diarrhoeal infections in
      Shanghai, correcting incidences of massively underdiagnosed DP species with
      accuracy approaching that of sequencing-based methods. The most frequent DPs were
      enteropathogenic Escherichia coli, rotavirus and Campylobacter jejuni. DP-HMGS
      detected two additional causes of infectious diarrhoea that were previously
      missed by routine culture-based methods: enterohemorrhagic E. coli and Yersinia
      enterocolitica. We demonstrated the age dependence of specific DP distributions,
      especially the distributions of rotavirus, intestinal adenovirus and Clostridium
      difficile in paediatric patients as well as those of dominant bacterial
      infections in adults, with a distinct "top 3" pattern for each age group.
      Finally, the multiplexing capability and high sensitivity of DP-HMGS allowed the
      detection of infections co-induced by multiple pathogens (approximately 1/3 of
      the cases), with some DPs preferentially co-occurring as infectious agents.
      Conclusions: DP-HMGS has been shown to be a rapid, specific, sensitive and
      appropriate method for the simultaneous screening/detection of polymicrobial DP
      infections in faecal specimens. Widespread use of DP-HMGS is likely to advance
      routine diagnostic and clinical studies on the aetiology of acute diarrhoea.

PMID- 30214490
TI  - Magnetic resonance imaging scans are not a reliable tool for predicting
      symptomatic acromioclavicular arthritis.
AB  - Background: We investigated whether magnetic resonance imaging (MRI) scans can
      accurately diagnose arthritis of the acromioclavicular joint (ACJ) because it has
      recently been suggested that bone marrow oedema on MRI scans is a predictive sign
      of symptomatic ACJ arthritis. Methods: The MRI scans of 43 patients (50
      shoulders) who underwent ACJ excision for clinically symptomatic ACJ arthritis
      were compared to a control group of 43 age- and sex-matched patients (48
      shoulders) who underwent an MRI scan for investigation of shoulder pain but did
      not have clinical symptoms or signs of ACJ arthritis. The scans were evaluated by
      an experienced musculoskeletal radiologist, who was blinded to the examination
      findings. Results: Bone marrow oedema was present in only 15 (30%) shoulders in
      the ACJ excision group, although this was higher than the six shoulders in the
      asymptomatic group (p = 0.03). Forty-one (82%) shoulders in the symptomatic group
      had grade III/IV ACJ arthritis compared to 31 (65%) in the asymptomatic group (p
      = 0.05). However, 44 out of 48 (92%) shoulders in the asymptomatic group had
      signs of osteoarthritis on MRI scans. Conclusions: In contrast to recent reports,
      the present study shows that MRI is not helpful in making the diagnosis of ACJ
      arthritis. A focused history and clinical examination should remain the mainstay
      for surgical decision making. Level of evidence: Level 3.

PMID- 30214491
TI  - Is the Walch B3 glenoid significantly worse than the B2?
AB  - Background: The Walch B3 glenoid is theorized to be a progression of the B2
      biconcave pattern. The present study aimed to compare glenoid indices between B2
      and B3 patterns. We hypothesized that the B3 pattern would have significantly
      worse retroversion, inclination and medialization. Methods: Computed tomography
      scans of 50 patients with B2 erosions [mean (SD) age 68 (9) years; 25 male] and
      50 patients with B3 erosions [mean (SD) age 72 (8) years; 22 males] were
      converted into three-dimensional reconstructions. Retroversion, inclination,
      medialization and humeral head subluxation were compared. Results: The data
      demonstrated no statistically significant differences [mean (SD)] between groups
      when assessing retroversion: B2 = 21 (8) degrees , B3 = 24 (7) degrees  (p =
      0.602); glenoid inclination: B2 = 9 (6) degrees , B3 = 8 (6) degrees  (p =
      0.967); or medialization: B2 = 12 (4) mm, B3 = 14 (4) mm (p = 0.384). In the B2
      group, the mean (SD) humeral head subluxation was 80% (10%) according to the
      scapular plane and 55% (9%) according to the glenoid plane, which was not
      statistically different from the B3 group with a mean (SD) humeral head
      subluxation of 81% (7%) according to the scapular plane (p = 0.680) and 54% (7%)
      according to the glenoid plane (p = 0.292). Conclusions: These results
      demonstrated no significant differences between the B2 and B3 erosion patterns,
      with respect to the glenoid indicies measured. The aetiology of the B3 glenoid
      cannot be completely explained by progression of wear in a B2 glenoid.

PMID- 30214492
TI  - The influence of age and unreported symptoms on the Oxford Shoulder Score.
AB  - Background: One potential limitation of interpreting the Oxford Shoulder Score
      (OSS) in longitudinal studies is that the observed score may be influenced by age
      and other variables, which may change over time. The purpose of the present study
      was to investigate the influence of increasing age and unreported non-shoulder
      upper limb and neck symptoms on the OSS. Methods: We collected OSS data from a
      sample of our ethnically diverse local population. All subjects indicated whether
      they suffered from any neck, shoulder, elbow or wrist symptoms for which they had
      not sought a medical opinion. Those reporting no symptoms formed the asymptomatic
      group. Results: We found a significant decline in OSS with increasing age in the
      whole study population, as well as in both the asymptomatic and symptomatic
      groups with previously unreported symptoms: Spearman correlation coefficient = 
      0.27, -0.28 and -0.33 respectively (p < 0.001). The median OSS in the
      asymptomatic group was 48 [interquartile range (IQR) 48 to 48]. This was
      significantly higher than the symptomatic group, with a median OSS of 46 (IQR 40
      to 47) (p < 0.001). Conclusions: We found the OSS to be affected by non-shoulder
      upper-limb and neck pathology as well as age. Within the limitations of the OSS,
      the differences we found do not exceed the minimal important change.

PMID- 30214493
TI  - Paediatric axillary artery pseudo-aneurysm after simple shoulder dislocation.
AB  - We report the unique case of a 14-year-old male with axillary artery pseudo
      aneurysm associated with brachial plexus compression after a simple shoulder
      dislocation. Following shoulder reduction under anaesthetic, the child was
      discharged on chemical deep vein thrombosis (DVT) prophylaxis. However,
      progressive shoulder swelling and upper limb neurological symptoms developed. A
      multi-disciplinary approach was taken to diagnose and treat this complication.
      After stopping the anti-coagulants, a combination of endovascular stent-graft and
      open surgical decompression of the brachial plexus was employed. Paediatric
      guidelines on DVT prophylaxis are scarce but DVT has never been reported in
      children following upper limb trauma.

PMID- 30214494
TI  - The reliability and validity of goniometric elbow measurements in adults: A
      systematic review of the literature.
AB  - Background: The universal goniometer is a simple measuring tool. With this review
      we aimed to investigate the reliability and validity of the universal goniometer
      in measurements of the adults' elbow. Methods: Preferred Reporting Items for
      Systematic reviews and Meta-Analysis guidelines were followed and our study
      protocol was published online at PROSPERO. A literature search was conducted on
      relevant studies. Methodological quality was assessed using the Quality Appraisal
      of Diagnostic Reliability (QAREL) scoring system. Results: Out of 697 studies
      yielded from our literature search, 12 were included. Six studies were rated as
      high quality. The intrarater reliability intraclass correlation coefficient
      ranged from 0.45 to 0.99, the interrater reliability ranged from intraclass
      correlation coefficient 0.53-0.97. One study providing instructions on
      goniometric alignment did not find a difference in expert versus non-expert
      examiners. Another study in which examiners were not instructed found a higher
      interrater reliability in expert examiners. One study investigating the validity
      of the goniometer in elbow measurements found a maximum standard error of the
      mean of 11.5 degrees  for total range of motion. Discussion: Overall, the studies
      showed high intra- and interrater reliability of the universal goniometer. The
      reliability of the universal goniometer in non-expert examiners can be increased
      by clear instructions on goniometric alignment.

PMID- 30214495
TI  - The short-term effect of swimming training load on shoulder rotational range of
      motion, shoulder joint position sense and pectoralis minor length.
AB  - Background: Shoulder pain or injury is the most common issue facing elite
      competitive swimmers and the most frequent reason for missed or modified
      training. Literature suggests that highly repetitive upper limb loading leads to
      inappropriate adaptations within the shoulder complex. The most likely
      maladaptations to occur are variations in shoulder rotational range of motion,
      reduction in joint position sense and shortened pectoralis minor length. This has
      yet to have been confirmed in experimental studies. The aim of this study was to
      investigate the short-term effects of swimming training load upon internal and
      external rotation range of motion, joint position sense and pectoralis minor
      length. Method: Sixteen elite swimmers training in the British Swimming World
      Class programme participated. Measures of internal and external range of motion,
      joint position sense error score and pectoralis minor length were taken before
      and after a typical 2 h swimming session. Results: Following swimming training
      shoulder external rotation range of motion and pectoralis minor length reduced
      significantly (-3.4 degrees , p = <0.001 and -0.7 cm, p = <0.001, respectively),
      joint position sense error increased significantly (+2.0 degrees  error angle, p
      = <0.001). Internal rotation range of motion demonstrated no significant change (
      0.6, p = 0.53). Discussion: This study determined that elite level swimming
      training results in short-term maladaptive changes in shoulder performance that
      could potentially predispose them to injury.

PMID- 30214496
TI  - Subpectoral biceps tenodesis using a novel anterior cortical button technique.
AB  - Background: Various surgical treatments are described in the literature for
      biceps pathology. Method: The techniques currently described for subpectoral
      tenodesis involve the use of suture anchors, interference screws, bicortical
      suture buttons or unicortical suture buttons. Results: A review of 31 patients
      with a subpectoral biceps tenodesis using the anterior cortical button technique
      is presented. Conclusions: We describe a novel technique, which provides an
      opportunity to obtain a robust cortical and intramedullary tenodesis, performed
      under direct vision without the risk of drilling the far cortex and therefore
      avoiding any potential for neurological injury. There is no cortical implant,
      which may lead to a diaphyseal stress riser and subsequent fracture risk.

PMID- 30214498
TI  - Methodological issues on interobserver reliability of radiographic assessment
      after radial head arthroplasty.

PMID- 30214497
TI  - Sternoclavicular joint.
AB  - The sternoclavicular joint is a saddle shaped, synovial joint and is the only
      skeletal articulation between the axial skeleton and the upper limb. Here, a
      reviewis provided of the anatomy, biomechanics, traumatic and atraumatic
      conditions, and management options for the various conditions described.

PMID- 30214499
TI  - The kappa paradox.

PMID- 30214500
TI  - Corrigendum to: Investigation and Management of Periprosthetic Joint Infection in
      the Shoulder and Elbow: Evidence and consensus based guidelines of the British
      Elbow and Shoulder Society.
AB  - [This corrects the article DOI: 10.1177/1758573218772976.].

PMID- 30214502
TI  - Nerve conduction study of the association between glycemic variability and
      diabetes neuropathy.
AB  - Background: It remains unclear whether glycemic variability is related to
      diabetes microvascular disease, especially diabetes peripheral neuropathy (DPN).
      We investigated the association between glycemic variability and DPN with type 1
      or 2 diabetes. Methods: Forty patients (23 males and 17 females; aged 34-79
      years) underwent continuous glucose monitoring (CGM) and a nerve conduction study
      (NCS). Glycemic variability was estimated by mean amplitude of glycemic
      excursions (MAGE) in CGM. DPN was quantitatively evaluated by NCS in the median,
      tibial, sural and medial plantar nerves. Results: MAGE had a significantly
      positive correlation with disease duration and low-density lipoprotein
      cholesterol level (r = 0.462, p = 0.003; and r = 0.40, p = 0.011, respectively),
      and a significantly negative correlation with BMI and medial plantar compound
      nerve action potential amplitude (r = - 0.39, p = 0.012; and r = - 0.32, p =
      0.042, respectively). Multivariate linear regression analysis with adjustment for
      clinical background showed that MAGE (beta = - 0.49, p= 0.007) was independently
      associated with a higher risk of medial plantar neuropathy. Conclusions: Glycemic
      variability may be an independent risk factor for DPN.

PMID- 30214501
TI  - Characterization of spontaneously-developed non-alcoholic fatty liver disease in
      aged rhesus monkeys.
AB  - Background: Non-alcoholic fatty liver disease (NAFLD) is a global epidemic
      afflicting 20-30% in the general population. The animal model of NAFLD available
      at the present are less clinically relevant. In this study. We aimed to establish
      a NAFLD model of rhesus monkeys and develop an ultrasonographic steatosis score
      (USS) system to grade hepatic steatosis in this model. Methods: We performed
      hepatic ultrasonography and blood biochemical tests on 86 rhesus monkeys with and
      without metabolic syndrome (MetS), among which 45 animals were further assessed
      by histopathological analysis. Results: The liver histological features of rhesus
      monkeys NAFLD were resemble to those of NAFLD patients. There was a close
      correlation between the histological steatosis grade and the USS (Spearman's
      coefficient, 0.705, p < 0.001). The USS sensitivity was 87.5% and the specificity
      was 94.6% when the cut-off was USS2. In addition, the prevalence of MetS was
      significantly higher in the USS2-3 group. Multiple risk factors of
      cardiometabolic disease, including obesity, insulin resistance and dyslipidemia
      were significantly correlated with the USS. Conclusions: NAFLD was developed
      spontaneously among aging in rhesus monkeys (with increased prevalence in the
      MetS monkeys), which provided an ideal model for NAFLD. The newly developed USS
      system can be used to evaluate fatty liver in the rhesus monkey. The model as
      well as the noninvasive assessment methodology will provide a powerful tool for
      mechanistic studies and preclinical test of novel therapies for NAFLD.

PMID- 30214503
TI  - MicroRNA-124 inhibits cell proliferation, invasion and migration by targeting
      CAV1 in bladder cancer.
AB  - MicroRNAs (miRs) may have promotive or suppressive roles in various human cancers
      types, but the molecular mechanisms underlying the role of miR-124 in bladder
      cancer (BC) progression have remained largely elusive. In the present study, it
      was observed that miR-124 was significantly downregulated in BC tissues compared
      with that in adjacent non-neoplastic tissues. Furthermore, its expression was
      also reduced in several human BC cell lines (T24, HT-1376 and 5637) compared with
      that in the normal bladder epithelial SV-HUC-1 cell line. A low expression of miR
      124 in BC patients was significantly associated with advanced malignancy and a
      poor prognosis. Caveolin 1 (CAV1) was identified as a novel target gene of miR
      124, and the expression of CAV1 was negatively regulated by miR-124 in T24 cells.
      Furthermore, CAV1 was identified to be significantly upregulated in BC tissues
      and cell lines, and a negative correlation was observed between the expression of
      miR-124 and CAV1 in BC tissues. Furthermore, restoration of miR-124 expression
      significantly inhibited the proliferation, migration and invasion of T24 cells,
      and these effects were impaired following overexpression of CAV1. Taken together,
      the present results demonstrate that miR-124 has a suppressive role in the
      proliferation, migration and invasion of BC cells by targeting CAV1, which
      suggests that miR-124 is a potential therapeutic candidate for BC.

PMID- 30214504
TI  - MERS associated with bacterial translocation in a pediatric patient with
      congenital portal vein hypoplasia: A case report.
AB  - A case of mild encephalitis/encephalopathy with a reversible splenial lesion
      (MERS) in a female child who developed bacterial translocation from a congenital
      portal vein hypoplasia is reported. The patient was diagnosed as having portal
      hypertension after examinations and laboratory results showing splenomegaly and
      thrombocytopenia at the age of 1 year. The patient required three endoscopic
      variceal ligation (EVL) surgeries before the age of 9 due to development of
      multiple esophageal varices. After the second and third EVL procedures, she
      developed septicemia, possibly due to bacterial translocation associated with the
      administration of general anesthesia. The day after the third EVL, the patient
      presented with high fever and neurological disturbances (altered consciousness).
      Magnetic resonance imaging detected abnormal intensities in the corpus callosum
      ampulla and cerebral white matter, which suggested a diagnosis of MERS type 2.
      Considering this clinical course, the possible association between bacterial
      translocation and MERS in a patient with congenital portal vein hypoplasia and
      portal hypertension is discussed.

PMID- 30214505
TI  - Cytotoxicity of local anesthetics on rabbit adipose-derived mesenchymal stem
      cells during early chondrogenic differentiation.
AB  - Local anesthetics (LAs) are commonly used to provide peri-operative pain control
      in the peripheral joints. In the field of regenerative medicine, adipose-derived
      mesenchymal stem cells (ADMSCs) are gaining attention as a cellular source for
      repair and regeneration in degenerative diseases. However, previous studies have
      demonstrated that the commonly used drugs lidocaine, ropivacaine, bupivacaine and
      mepivacaine may be toxic to human chondrocytes, which has raised concerns over
      whether they exert similar negative effects on ADMSCs during early chondrogenic
      differentiation. In the present in vitro study, the cytotoxicity of different LAs
      to ADMSCs was determined during early chondrogenic differentiation. At
      concentrations similar to those after physiological dilution once injected into
      the degenerative tissues, LAs (1% lidocaine, 0.5% bupivacaine, 0.5% ropivacaine
      or 2% mepivacaine) and PBS (control group) were incubated with rabbit ADMSCs
      (rADMSCs) for 60 min. Following further culture for 3 or 7 days, the cell
      viability, apoptosis and morphological alterations of chondrogenic
      differentiation were measured by determining the mitochondrial activity, by flow
      cytometric analysis, Safranine Fast Green double staining and reverse
      transcription-quantitative polymerase chain reaction of chondrogenesis-associated
      genes. The results indicated that the mitochondrial activity in rADMSC was
      decreased and the apoptotic rate was increased, following treatment with LAs
      (P<0.05). Lidocaine (1%) was less cytotoxic to rADMSCs during early
      chondrogenesis compared with other LAs. The expression levels of chondrogenesis
      associated markers, including collagen I, collagen III and sex-determining region
      Y box 9 were all decreased at day 3 following exposure to LAs compared with the
      control group (P<0.05). The expression levels of these chondrogenesis-associated
      genes began to increase on day 7 following exposure but remained lower compared
      with the control group (P<0.05). Of note, 2% mepivacaine and 1% lidocaine
      exhibited a less pronounced negative effect on chondrogenesis-associated gene
      expression compared with other LAs. Therefore, the present study concluded that
      LAs are cytotoxic to rADMSCs during early chondrogenesis. Attention should be
      paid to the different types of LA selected in conjunction with ADMSC injection
      therapy.

PMID- 30214506
TI  - Inhibition of endogenous hydrogen sulfide production exacerbates the inflammatory
      response during urine-derived sepsis-induced kidney injury.
AB  - The aim of the present study was to investigate the effects of endogenous H2S on
      the inflammatory response in kidneys following urine-derived sepsis-induced
      injury. A rabbit model of urine-derived sepsis was established by injecting
      Escherichia coli into the ligated ureter. Rabbits were randomly divided into the,
      control, sham, sepsis and DL-propargylglycine (PAG)-treated sepsis groups. The
      same surgical procedure except for the bacteria injection was performed for the
      sham group, while the control group was fed on normal diet without any additional
      treatments. The monitoring of vital signs, routine blood examinations and kidney
      function tests were performed prior to surgery and at 12, 24, 36 and 48 h
      following surgery. The serum H2S concentration and kidney cystathionine-gamma
      lyase (CSE) activity were determined following surgery. Pathological alterations
      were assessed by hematoxylin and eosin (H&E) staining, and the expression levels
      of inflammation-associated cytokines were detected by western blot analysis. The
      results demonstrated that rabbits in the sepsis and PAG groups exhibited a
      significant increase in rectal temperature, heart rate and respiratory rate
      following surgery when compared with the sham group; with the PAG group
      demonstrating the greatest increase. In addition, white cell counts and
      creatinine and urea nitrogen levels were significantly elevated following surgery
      in the sepsis and PAG groups when compared with the sham group. The serum H2S
      concentration and kidney CSE activity were significantly reduced in the sepsis
      group compared with the sham group, and a significant decrease in the levels of
      these factors were observed in the PAG group compared with the sepsis group. H&E
      staining indicated obvious structural abnormalities in kidney tissues in the
      sepsis group, which were exacerbated by PAG treatment. In addition, PAG treatment
      significantly increased the expression levels of nuclear factor-kappaB and
      interleukin-6, and decreased transforming growth factor-beta1 expression when
      compared with the sepsis group. In conclusion, PAG significantly exacerbated
      urine-derived sepsis-induced kidney injury potentially via altering the
      expression of inflammation-associated cytokines.

PMID- 30214507
TI  - Effect of parathyroid hormone on cardiac function in rats with cardiomyopathy.
AB  - The present study investigated the role of parathyroid hormone (PTH) in non
      ischemic cardiomyopathy (CM) and its underlying mechanism. A total of 30 Sprague
      Dawley male rats were randomly divided into a control group (n=6) and an
      experimental group (n=24). To induce CM in the rats of the experimental group, 2
      mg/kg Adriamycin (ADR) was administered intraperitoneally with 5 equal injections
      every third day followed by 5 weekly injections resulting in a cumulative dose of
      20 mg/kg. Following establishment of the model, rats in the experimental group
      were subdivided into a PTH-untreated CM group that received daily normal saline
      subcutaneous injections for 7 days and three treated CM groups that received
      daily subcutaneous injections of 5, 10, or 20 ug/kg of recombinant PTH for 7
      days. Rats in the control group accordingly received intraperitoneal and
      subcutaneous injections of normal saline. Blood sample analysis revealed that B
      type natriuretic peptide (BNP), troponin T, C-reactive protein (CRP), creatinine
      and phosphorus concentrations were increased in the PTH-untreated CM group
      compared with that in the control group, whereas PTH and calcium concentrations
      were decreased. Administration of PTH dose-dependently decreased BNP, CRP,
      creatinine and phosphorus levels, and increased PTH and calcium levels. Notably,
      there were significant differences in PTH, BNP, troponin T, CRP, creatinine,
      calcium, and phosphorus levels among the rats in the five groups (P<0.01).
      Cardiac ultrasonography results indicated that the left ventricular ejection
      fraction (LVEF) was significantly decreased in rats treated with ADR compared
      with the rats from the control group (P<0.01). However, the LVEF gradually
      recovered with elevated PTH treatment doses. The overall differences of LVEF and
      left ventricular end-systolic volume in the five experimental groups were
      statistically significant (P<0.01). Furthermore, there were dose-dependent
      increases in LV mass and left ventricular end-diastolic volume in PTH-treated
      rats; however, the differences between any two groups did not reach statistical
      significance (P>0.05). Immunohistochemical staining and western blot analysis
      using an anti-PTH polyclonal antibody was performed to evaluate the protein
      expression levels of PTH in myocardial tissues. The mRNA expression levels of PTH
      and BNP were measured using reverse transcription-quantitative polymerase chain
      reaction. The results demonstrated that the mRNA and protein expression levels of
      PTH in myocardial tissues were significantly decreased in ADR-treated rats
      compared with the levels in the control group rats. Injection of recombinant PTH
      significantly increased PTH expression and reduced BNP expression in dose
      dependent manners (P<0.05). These findings demonstrated that PTH can improve
      cardiac function in rats with ADR-induced CM, suggesting a potential therapeutic
      application for PTH in non-ischemic CM.

PMID- 30214508
TI  - The function of MMP-28/TGF-beta induced cell apoptosis in human glioma cells.
AB  - The aim of the present study was to assess the expression status of matrix
      metalloproteinase (MMP)-28 and to investigate its molecular mechanisms in glioma
      cells. MicroRNA (miRNA) reverse transcription-quantitative polymerase chain
      reaction was used to analyze the expression of MMP-28 and transforming growth
      factor (TGF)-beta expression in glioma patients and healthy volunteers. MTT and
      Transwell assays were conducted to determine cell growth and metastasis,
      respectively. Annexin V/propidium iodide staining was also employed to measure
      cell apoptosis. MMP-28 and TGF-beta protein expression were measured using
      western Blot analysis. The results indicated that MMP-28 and TGF-beta expression
      was downregulated in glioma patients, when compared with the normal group.
      Overall survival and disease-free survival of patients with a low expression of
      MMP-28 were lower than those with high MMP-28 expression. Overexpression of MMP
      28 induced TGF-beta protein expression, while downregulation of MMP-28 suppressed
      TGF-beta protein expression in glioma cell. The downregulation of MMP-28 reduced
      the cell growth and apoptosis of glioma cell via the suppression of TGF-beta. By
      contrast, upregulation of MMP-28 induced cell growth and reduced the apoptosis of
      glioma cells by activating TGF-beta. In addition, the TGF-beta inhibitor
      attenuated the effects of MMP-28 in glioma cells. Collectively, the results
      indicated that MMP-28 was able to induce TGF-beta in human glioma cells.

PMID- 30214509
TI  - Effect of abnormal GpG methylation in the second trimester of pregnancy on
      adverse health risk of offspring.
AB  - Effect of abnormal GpG methylation in amniotic fluid cells during the second
      trimester of pregnancy on adverse health risk of offspring was investigated. In
      total, 237 sets of amniotic fluid cells were collected from patients who received
      prenatal diagnosis in the Third Affiliated Hospital of Guangzhou Medical
      University (Guangzhou, China) from April 2010 to October 2011. Among them, 156
      sets were from singleton and 81 sets were from twins. H19 gene was amplified by
      PCR, and the product was purified and pyrosequencing was used to detect the DNA
      methylation level of GapG. Follow-up records of the birth outcomes of pregnant
      women's offspring were collected. Positive rate of DNA amplification in 200 cases
      of amniotic fluid cells was 84.4% (200/237). Average age of singleton pregnancies
      was higher than that of twins (P<0.05), and no significant differences were found
      in gestational age and PCR amplification rate (P>0.05). There was no difference
      in the methylation level of GapG between singleton and twins (P>0.05), but the
      abnormal methylation rate of GapG1 in twin fetuses was significantly higher than
      that of singleton (20.3 vs. 3.6%, chi2=8.364, P=0.004). Offspring sex, singleton
      or twins, mode of delivery, time of pregnancy, and low birth weight showed no
      significant effect on GapG methylation level of H19 in the second trimester of
      pregnancy. No offspring deformities were found regardless of the increased or
      decreased degree of methylation (P>0.05). The number of fetuses born may cause
      abnormal GapG1 methylation, but no effect of GapG methylation on the adverse
      health risk of offspring was found.

PMID- 30214510
TI  - A comparison of CD105 and CD31 expression in tumor vessels of hepatocellular
      carcinoma by tissue microarray and flow cytometry.
AB  - Tumor endothelial cells (TECs) have been isolated from solid tumors by using
      immunological magnetic beads and magnetic active cell sorting, and lead to a more
      precise way to investigate tumor angiogenesis as well as screening of vascular
      targeting drugs. However, the question of which endothelial marker is a stable
      molecular signature in TECs and can be used for the isolation of TECs from tumor
      tissues remains unclear. In this study, we investigated the endothelial markers
      CD105 and CD31 in the tumor vessels from 90 patients with hepatocellular
      carcinoma (HCC) by tissue microarray, in addition to their expression in TECs
      isolated from fresh tissues resected from 11 patients with HCC by flow cytometry
      and confocal microscopy. The results revealed that among 90 cases of TMA, all
      tumor vessels were CD31 positive whereas 39 cases (43.3%) had little or no CD105
      expression in tumors and their vessels but not peritumoral tissue spots, and that
      among these 39, 29 cases (74.4%) were poor-differentiated HCC. These findings
      were further verified by flow cytometry and confocal analysis of TECs isolated
      from HCC. Overall, the results suggested that CD105 may not be expressed in TECs
      derived from poor-differentiated HCC cases. In addition, combined with previous
      studies in which CD105 is not only expressed in TECs, but also in tumor cells,
      the results indicated a high risk of contamination with CD105+ tumor cells. Thus,
      there is a limitation to the use CD105 as an endothelial marker for the isolation
      of TECs.

PMID- 30214511
TI  - Application of karyotype analysis combined with BACs-on-Beads for prenatal
      diagnosis.
AB  - This study explored the clinical application of karyotype analysis combined with
      BACs-on-Beads (BoBs) technology in prenatal diagnosis. A total of 558 pregnant
      women who were admitted to Xuzhou Maternity and Child Health Care Hospital from
      July 2015 to June 2017 were enrolled in this study. All the subjects underwent
      amniocentesis. BoBs assay was performed for subjects in the observation group,
      and karyotype analysis was performed for subjects in the control group. The main
      technical indicators of subjects in the two groups were summarized, and cases of
      chromosome abnormalities were further evaluated. Clinical follow-up of their
      pregnancy and neonatal birth was undertaken. Finally, the chromosomal
      manifestations of these patients were compared with those of normal male and
      normal female, as well as common chromosomal abnormalities. All 558 pregnant
      women underwent amniocentesis again. Karyotype analysis combined with BoBs assay
      of amniotic fluid was performed. Cases of chromosomal abnormalities detected
      were: 75 cases of trisomy 21, 20 cases of trisomy 18, 1 case of trisomy 13, 27
      cases of sex chromosomal abnormalities, 12 cases of balanced chromosome
      translocation, and 2 cases of chromosome microdeletion. The results indicated
      that karyotype analysis combined with BoBs technology for prenatal diagnosis was
      easy to perform, and provided quick results with high accuracy. The two testing
      methods were complementary to each other, which significantly improved the
      diagnostic rate of chromosomal abnormalities thus reducing birth defects and
      guiding continued pregnancy of high-risk pregnant women.

PMID- 30214512
TI  - Chlorogenic acid in the oxidative stress injury triggered by Shuang-Huang-Lian
      injection.
AB  - Injections of Chinese herbs are a novel approach to prepare traditional Chinese
      medicines. However, as injections of Chinese herbs have been extensively used,
      adverse drug reactions (ADRs) have been on the increase. Additionally, the
      mechanism for injections of Chinese herbs remains unclear. This study explored
      the potential role played by chlorogenic acid (CGA) in initiating oxidative
      stress injury triggered by the utilization of injections of Chinese herbs and the
      underlying mechanism. A total of 90 male Wistar rats were raised for varying
      periods by using Shuang-Huang-Lian (SHL) injection or CGA in diverse dosages.
      Western blot analysis examined the expression of nicotinamide adenine
      dinucleotide phosphate oxidase subunits, spectrophotometry was used to examine
      the activity taken by catalase, ELISA was used to examine the concentrations of
      inflammatory factors in serum, and intravital microscopy was employed to examine
      the microcirculation. The results showed that the excessive peroxide production
      induced by CGA in high-dose or SHL in the venule walls may well be through
      nicotinamide adenine dinucleotide phosphate oxidase along with a decline in the
      activity of catalase, and led to imbalance of basal levels of pro-(TNF-alpha) and
      anti-(IL-10) inflammatory cytokines. On the basis of the aforementioned results,
      the mechanism hidden behind the adverse effects of CGA induced by irrational use
      of Chinese herbal injection can be identified from a deeper perspective.

PMID- 30214513
TI  - Tanshinone IIA inhibits cell proliferation and tumor growth by downregulating
      STAT3 in human gastric cancer.
AB  - Gastric cancer is the third leading cause of cancer-associated deaths worldwide.
      Research into the underlying mechanisms of gastric cancer is essential for the
      development of novel therapeutic agents to improve the prognoses of patients with
      gastric cancer. Tanshinone IIA (Tan IIA) is the pure extract of Danshen root
      (Salvia miltiorrhiza) and has been report to inhibit the proliferation of gastric
      cancer cells; however, the intrinsic underlying mechanisms remain unclear. The
      aim of the present study was to investigate whether Tan IIA has a direct anti
      cancer effect in gastric cancer cells and determine the underlying mechanisms
      responsible. The results revealed that Tan IIA effectively inhibits proliferation
      in three human gastric cancer cell lines (SNU-638, MKN1 and AGS) in a time- and
      dose-dependent manner. Furthermore, Tan IIA treatment induced an increase in
      apoptosis, B-cell lymphoma (Bcl-2)-associated protein X expression and cleaved
      caspase-3 levels, as well as a decrease in Bcl-2 expression. Treatment with Tan
      IIA inhibited Furthermore, treatment with Tan IIA significantly inhibited the
      phosphorylation of signal transducer and activator of transcription 3 (STAT3),
      which may be responsible for the changes in apoptosis gene expression. However,
      overexpression of STAT3 significantly ameliorated the Tan IIA-induced suppression
      of cell growth and apoptosis. A nude mouse xenograft model was constructed and
      the results revealed that intraperitoneal Tan IIA treatment for 28 days
      significantly inhibited tumor growth and STAT3 activation. The results of the
      present study suggest that Tan IIA exerts potent anti-cancer activity in gastric
      cancer cells and this effect is mediated by the downregulation of STAT3
      activation.

PMID- 30214514
TI  - Thiazolidinedione induces a therapeutic effect on hepatosteatosis by regulating
      stearoyl-CoA desaturase-1, lipase activity, leptin and resistin.
AB  - Hepatosteatosis is a disease present worldwide, which presents a number of health
      problems. Recently, thiazolidinedione (TZD) has been used as a therapy for lipid
      disorders. The present study demonstrates the potential of TZD as a treatment for
      hepatosteatosis and its mechanism of action, particularly focusing on its role in
      lipid metabolism. A total of 60 (80-90 g) rats were divided into three groups: A
      normal group with a standard diet, a high-fat, high-carbohydrate diet (HFCD)
      group or a HFCD+TZD group (n=20/group). The HFCD induced hepatosteatosis over a
      period of 12 weeks and the HFCD+TZD group were administered TZD in weeks 13-16.
      Blood and tissue samples were collected to measure hepatic function, the lipid
      profile, metabolism and hormone biomarkers, including serum triglyceride (TG),
      lipoprotein lipase (LPL), stearoyl-CoA desaturase (SCD-1), leptin and resistin.
      The HFCD-fed rats exhibited a significant increase in serum TG, total
      cholesterol, low-density lipoproteins, alanine transaminase and bilirubin
      compared with the normal group as well as a significant decrease in high-density
      lipoprotein. In addition, serum leptin and resistin were significantly elevated
      in the HFCD group compared with the normal group. The administration of TZD
      significantly increased SCD-1 activity and significantly inhibited LPL activity.
      It also attenuated the changes in the lipid profiles and normalized serum leptin
      and resistin levels. The results of the present study indicated that HFCD induced
      lipid abnormalities associated with hypertriglyceridemia, hypercholesterolemia
      and hepatosteatosis. These changes resulted from disruption to leptin and
      resistin, which may be due to alterations in LPL and SCD-1 activity. TZD
      mitigated the effects of HFCD-induced hepatosteatosis, indicating a possible
      regulatory effect of TZD in the development of hepatosteatosis. The authors
      suggest that the manipulation of SCD-1 and lipase by TZD may be useful as a
      treatment for hepatosteatosis.

PMID- 30214515
TI  - Co-culture of bone marrow stromal cells and chondrocytes in vivo for the repair
      of the goat condylar cartilage defects.
AB  - This study explored the feasibility of inducing the differentiation of BMSCs into
      chondrocytes through co-culture with chondrocytes in hydrogel constructs
      (Pluronic F-127 gel) in vivo for the repair of goat mandibular condylar cartilage
      defects. Chondrocytes and BMSCs were isolated from goat auricular cartilage and
      bone marrow, respectively, and were mixed at a ratio of 3:7. BMSCs were labelled
      with green fluorescence protein (GFP) using a retrovirus vector for tracing.
      Mixed cells were re-suspended in 30% Pluronic F-127 at a concentration of 5*107
      cells/ml to form a gel-cell complex. The gel-cell complex was implanted into the
      temporomandibular joint condylar articular cartilage defects. The whole
      temporomandibular joint and adjacent tissues were harvested at 4, 8, and 12 weeks
      after surgery, and gross observation, histology and collagen II expression were
      evaluated. In the co-culture group, cartilage-like tissues were formed, and
      abundant type II collagen could be detected by immunohistochemistry in the
      condylar cartilage defects. Confocal microscopy revealed that implanted GFP
      labelled BMSCs were embedded in cartilage-like tissues. The co-culture system
      described herein provides a chondrogenic microenvironment to induce the
      chondrogenic differentiation of BMSCs in vivo without any additional cellular
      factors.

PMID- 30214517
TI  - Effects of glucocorticoids combined with probiotics in treating Crohn's disease
      on inflammatory factors and intestinal microflora.
AB  - This study investigated the effect of glucocorticoids combined with probiotics on
      inflammatory factors and intestinal microflora in the treatment of Crohn's
      disease. Eighty-three patients with Crohn's disease were selected from March 2015
      to December 2017 in PLA Army General Hospital (Beijing, China). A total of 83
      patients were randomly divided into the control group and treatment group.
      Patients in the control group were treated with routine treatment of oral
      sulfasalazine. Besides oral sulfasalazine, patients in the treatment group were
      treated with probiotics combined with glucocorticoids. At the same time, a total
      of 40 healthy individuals were selected to serve as the healthy group (received
      no treatment). Clinical efficacy, changes of inflammatory factors, incidence of
      infection and changes of intestinal flora were compared between the different
      groups. After treatment, the levels of inflammatory factors in both groups
      significantly decreased, and the reduction in the treatment group significantly
      increased than that in the control group (P<0.05). The levels of inflammatory
      cytokines in the treatment group reached the levels of that in the healthy
      individuals after treatment. After treatment, the levels of yeast, enterococci
      and peptococcus of the two groups of patients were significantly decreased, while
      the level of lactobacillus was significantly increased, and the changes were more
      significant in the treatment group than those in the control group. After
      treatment, the number of intestinal flora in the treatment group reached that of
      the healthy individuals. Treatment efficiency of the treatment group was
      significantly higher than that of the control group, and the infection rate of
      the control group was significantly higher than that of the treatment group
      (P<0.05). The use of probiotics combined with glucocorticoid in the treatment of
      Crohn's disease can improve clinical curative effect, reduce the secretion of
      inflammatory factors and improve the level of intestinal flora, so as to achieve
      better outcomes compared with conventional method.

PMID- 30214516
TI  - Inhibition of RKIP aggravates thioacetamide-induced acute liver failure in mice.
AB  - Accumulating evidence has indicated that Raf kinase inhibitor protein (RKIP) is
      involved in several intracellular signaling pathways; its abnormal expression is
      associated with tumor progression and metastasis in several human neoplasms.
      However, the role of RKIP in acute liver injury has remained elusive. In the
      present study, acute liver failure was induced by thioacetamide in mice, and
      locostatin was used to interfere with RKIP expression. It was found that RKIP
      expression was significantly inhibited by locostatin. Down-regulation of RKIP
      expression resulted in severe liver injury and extensive release of alanine
      aminotransferase and aspartate aminotransferase. In addition, reduced RKIP
      expression significantly enhanced the levels of reactive oxygen species and the
      content of pro-inflammatory factors such as tumor necrosis factor-alpha as well
      as interleukin-6 and -1beta, and decreased the levels of nuclear factor E2
      related factor-2 and heme oxygenase-1. Furthermore, down-regulation of RKIP
      promoted the activation of the nuclear factor-kappaB and extracellular signal
      regulated kinase signaling pathways. In conclusion, the present study indicates
      an inverse correlation between RKIP level and the degree of hepatic injury, that
      is, a decrease in RKIP expression may exacerbate acute liver failure.

PMID- 30214518
TI  - The expression and correlation between chemokine CCL7 and ABCE1 in non-small cell
      lung cancer.
AB  - Lung cancer is a malignant disease, and has the highest incidence and mortality
      worldwide. Lung cancer is also a popular subject in the field of cancer research.
      The molecular mechanisms of lung cancer development, invasion and metastasis need
      to be determined to prolong survival times and improve the quality of life.
      Recent studies have demonstrated that ATP-binding cassette sub-family E member 1
      (ABCE1) is one of the factors that contributes to the development and metastasis
      of lung cancer, but the specific mechanism of this phenomenon remains unclear. A
      polymerase chain reaction microarray was used in the present study to screen for
      chemokine (C-C motif) ligand 7 (CCL7) expression in cell lines that highly
      expressed ABCE1, and the results showed that CCL7 was highly expressed in H1299
      cells (P<0.01). The expression of CCL7 and ABCE1 in lung cancer tissues obtained
      from 30 patients with non-small cell lung cancer (NSCLC) was higher than that in
      adjacent normal lung tissues (P<0.01), and a positive correlation between the
      expression levels of the two genes in NSCLC was observed. These findings indicate
      that ABCE1 is involved in the development and progression of lung cancer through
      the CCL7 signaling pathway.

PMID- 30214519
TI  - Protective effects of extracellular polymeric substances from Aphanizomenon flos
      aquae on neurotoxicity induced by local anesthetics.
AB  - The neurotoxicity of local anesthetics has received an increasing amount of
      attention and more effective therapeutic agents are required. Extracellular
      polymeric substances from Aphanizomenon flos-aquae (EPS-A) are high molecular
      weight polysaccharides. The present study aimed to elucidate the protective
      effects of EPS-A on neurotoxicity induced by local anesthetics in an
      intraperitoneal injection bupivacaine rat model. The results of
      immunohistochemical staining inicated that following intraperitoneal injection of
      EPS-A the levels of apoptosis and caspase-3 decreased, and the expression levels
      of microtubule-associated protein 1A light chain 3 (LC3) and beclin1 increased.
      In order to further clarify the mechanism of the EPS-A-mediated protection, the
      expression of key proteins associated with autophagy was investigated by western
      blotting. The results suggested that the ratio of LC3-II/LC3-I and the expression
      level of beclin1 increased. Taken together, the results indicated that EPS-A
      induced neuroprotective effects on bupivacaine-induced neurotoxicity. The
      underlying mechanism may be associated with the inhibition of apoptosis,
      upregulation of autophagy and improvement of cell survival. The results suggested
      that EPS-A may be a candidate neuroprotective agent against neurotoxicity caused
      by local anesthetics.

PMID- 30214520
TI  - Ginsenoside Rb1 administration attenuates focal cerebral ischemic reperfusion
      injury through inhibition of HMGB1 and inflammation signals.
AB  - High-mobility group box 1 (HMGB1) is released after focal cerebral
      ischemia/reperfusion (I/R), and aggravates brain tissue damage. Ginsenoside Rb1
      (Rb1), isolated from Panax ginseng, has been reported to inhibit I/R-induced cell
      death in the brain. The present study aimed to investigate the protective ability
      of GRb1 on focal cerebral I/R rats and to explore its further mechanisms. A
      middle cerebral artery occlusion (MCAO) rat model was established and treated
      with different doses of Rb1. The neurological deficits were examined after
      reperfusion, and TTC staining was applied to assess the infarct volume. Histology
      and TUNEL staining were performed to evaluate pathological changes and neuronal
      cell apoptosis in brain tissues. HMGB1 and levels of inflammatory factors and
      proteins, were examined by ELISA or western blotting. Rb1 treatment notably
      improved the neurological deficits in an MCAO model, accompanied by decreased
      infarct volume in the brain tissues. Histological examination revealed that the
      necrotic tissue area in MCAO rats was also diminished by Rb1 treatment. Apoptosis
      induced by cerebral I/R was also attenuated by Rb1 treatment via downregulation
      of cleaved caspase-3 and caspase-9 levels. HMGB1 release was inhibited by Rb1
      treatment in MCAO rats, and the levels of nuclear factor-kappaB, tumor necrosis
      factor-alpha, interleukin-6, inducible nitric oxide synthase and nitric oxide
      were also decreased. The present study suggests that Rb1 serves a protective role
      in I/R-induced cerebral-neuron injury, due to the decreased cerebral infarct
      volume of brain tissue. The mechanisms underlying these effects may be associated
      with the inhibition of HMGB1 inflammatory signals.

PMID- 30214521
TI  - Correlation between controlled lung collapse and early lung injury in dogs.
AB  - A new type of pulmonary sequestration ventilator was used to compare the
      relationship between controlled lung collapse and early lung injury in thoracic
      surgery for dogs. Eighteen experimental dogs were randomly divided into three
      groups (G1-G3 groups). After general anesthesia, the shunt balance in lung was
      controlled and the pulmonary sequestration tube was placed in the femoral artery
      and vein, and the Swan-Ganz tube was placed into the right internal jugular vein
      as well. Two-lung ventilation (TLV) was first performed for 20 min, followed by
      one-lung ventilation (OLV). The degree of collapse was 100% (G1), 90% (G2), and
      50% (G3). Blood samples were extracted from femoral artery and jugular vein prior
      to collapse (T0), and at 30 (T1), 60 (T2), and 120 (T3) min after collapse for
      blood gas analysis to determine the shunt ratio (Qs/Qt). Blood samples were also
      subjected to enzyme linked immunosorbent assay (ELISA) to determine serum tumor
      necrosis factor-alpha (TNF-alpha), intercellular immune adhesion molecule-1 (ICAM
      1) and interleukin-6 (IL-6) levels. Arterial blood pressure, heart rate,
      pulmonary artery pressure and other physiological indicators were monitored
      during the experiment. Lung tissues were collected at T3 to calculate the wet/dry
      weight ratio (W/D). Histopathological changes were observed and compared by
      microscopic observation and blind scoring of pathological section after
      hematoxylin and eosin (H&E) staining. There were no significant differences in
      the physiological indexes between the two groups during TLV (P>0.05). Mean
      pulmonary arterial pressure (MPAP) in G2 and G3 groups was significantly more
      stable than that in G1 group after OLV (P<0.05); shunt ratio Qs/Qt, W/D, and
      serum TNF-alpha, ICAM-1 and IL-6 levels in the lung were decreased; and the
      degrees of pulmonary edema, hemorrhage, inflammatory cell infiltration and lung
      injury were also decreased. There was no statistically significant difference in
      each index at each time-point between G2 and G3 groups (P>0.05). Compared with
      complete lung collapse (collapse degree: 100%), controlled lung collapse
      (collapse degree: 90% and 50%) can better reduce the intraoperative lung injury,
      but there was no significant difference between the collapse degrees of 90 and
      50%.

PMID- 30214522
TI  - Overexpression of TRIM44 is an independent marker for predicting poor prognosis
      in epithelial ovarian cancer.
AB  - Tripartite motif-containing 44 (TRIM44) has been demonstrated to be important in
      tumor metastasis and progression. However, the expression pattern and prognostic
      value of the expression of TRIM44 in epithelial ovarian cancer (EOC) remain to be
      fully elucidated. In the present study, the aim was to investigate the expression
      and clinical role of TRIM44 in EOC. A total of 109 patients, who underwent
      primary surgery with the goal of maximal tumor resection followed by standard
      combination chemotherapy with carboplatin and paclitaxel, were analyzed in the
      present study. The expression level of TRIM44 was determined by western blot
      analysis and immunohistochemistry in 109 ECO tissues. It was found that the
      expression of TRIM44 was low in normal tissues and high in EOC tissues.
      Univariate survival analysis showed that the overexpression of TRIM44 was
      significantly associated with International Federation of Gynecology and
      Obstetrics stage and lymph node metastasis (P<0.05). Kaplan-Meier analysis
      suggested that there was a significant difference in overall survival and disease
      free survival rates between patients with a high expression of TRIM44 and
      patients with a low expression of TRIM44. Patients with a high expression level
      of TRIM44 exhibited poorer overall survival and disease-free survival rates,
      compared with patients expressing a low level of TRIM44 (P<0.001). In addition,
      the results of the multivariate analysis revealed that the predictive value of
      the expression of TRIM44 was independent of other clinicopathological factors for
      predicting prognosis. These findings demonstrated that a high expression of
      TRIM44 was associated with the progression and prognosis of EOC.

PMID- 30214523
TI  - Effect of autophagy-associated proteins on the arecoline-induced liver injury in
      mice.
AB  - Arecoline can be used to treat diseases including glaucoma and tapeworm
      infection, however, long-term administration can cause severe adverse effects,
      including oral submucosal fibrosis, oral cancer, hepatic injury and liver cancer.
      Autophagy serves a role in these injuries. The present study established a mouse
      model of arecoline-induced hepatic injury and investigated the role of autophagy
      associated proteins in this injury. The results indicated that the expression
      levels of the autophagy marker protein microtubule associated protein 1 light
      chain 3 B (MAP1LC3B) and autophagy-promoting protein beclin 1 were elevated in
      the injured hepatic cells, while the expression levels of a well-known negative
      regulator of autophagy, mammalian target of rapamycin (mTOR), were reduced.
      Following treatment of the hepatic injury with glutathione, the liver function
      improved and liver damage was reduced effectively. Compared with the control
      group, the expression levels of both MAP1LC3B and beclin 1 were significantly
      upregulated in the glutathione-treated mice, but the expression of mTOR was
      significantly downregulated. It may be concluded that in the process of
      protecting against arecoline-induced hepatic injury, glutathione cooperates with
      mTOR and beclin 1 to accelerate autophagy, maintaining stable cell morphology and
      cellular functions.

PMID- 30214524
TI  - Correlation of CXCR4/CXCR7 signaling pathway with pre-eclampsia.
AB  - The possible role of C-X-C chemokine receptor type 4 (CXCR4)/CXCR7 signaling
      pathway in pre-eclampsia (PE) was investigated to study the expression of
      CXCR4/CXCR7 in serum of PE patients and its correlation and relationship with PE.
      Twenty patients with mild PE and 40 cases with severe PE enrolled into the PE
      group and 60 cases of the normal pregnancy group during the same period were
      selected as the objects of study. The changes in expression of serum CXCR4
      messenger ribonucleic acid (mRNA) and CXCR7 mRNA were detected by reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR), and CXCR4/CXCR7
      protein concentration in serum was determined by enzyme-linked immunosorbent
      assay (ELISA). The pregnancy termination time of gravid was earlier in the severe
      PE group than that in the normal pregnancy group (P<0.05); the mean arterial
      pressure (MAP), systolic pressure, diastolic pressure were higher in patients
      with mild and severe PE than those in the normal pregnancy group (P<0.05). The
      results of RT-qPCR showed that the mRNA expression of serum CXCR4 and CXCR7 in PE
      patients were distinctly higher than those in the normal pregnancy group
      (P<0.05). The expression level of CXCR4 mRNA was positively correlated with that
      of CXCR7 mRNA (r=0.567, P=0.02). The results of ELISA displayed that the content
      of CXCR4/CXCR7 in serum of patients with PE was remarkably higher than that in
      the normal pregnancy group (P<0.05); the expression of serum CXCR4/CXCR7 in
      patients with severe PE was higher than in those with mild PE (P<0.05). The
      expression level of serum CXCR4 protein was positively correlated with that of
      CXCR7 protein (r=0.563, P=0.01). The expression level of CXCR4/CXCR7 may be
      closely related to the formation of PE.

PMID- 30214525
TI  - Correlation of CCR5 and NLRP3 gene polymorphisms with renal damage due to
      hepatitis C virus-related cryoglobulinemia.
AB  - Correlation of C-C chemokine receptor type 5 (CCR5) and NACHT, LRR and PYD domain
      containing protein 3 (NLRP3) gene polymorphisms with renal damage due to
      hepatitis C virus (HCV)-related cryoglobulinemia were investigated. The 1:1
      matched case-control study design was adopted, 171 patients with renal damage due
      to HCV-related cryoglobulinemia were selected as the case group, and 171 patients
      without renal damage were selected as the control group. Polymerase chain
      reaction and restriction fragment length polymorphism (PCR-RFLP) analysis was
      used to detect the polymorphisms of locus rs1799987A/G in CCR5 gene and locus
      rs35829419A/C in NLRP3 gene of 171 pairs of HCV patients. SPSS 20.0 software was
      used for logistic regression analysis, and genetics package of the R programming
      language for Hardy-Weinberg equilibrium test. The frequencies of locus
      rs1799987A/G in CCR5 gene in the case group were 48.0 and 52.0%, while those in
      the control group were 47.9 and 52.1%; the frequencies of locus rs35829419A/C in
      NLRP3 gene were 55.8 and 44.2%, while those in the control group were 55.3 and
      44.7%. The results of logistic regression analysis showed that the distribution
      of CCR5 gene polymorphism in the case group was statistically different from that
      in the control group (P<0.05), which had a statistical correlation with the renal
      damage due to HCV-related cryoglobulinemia (P<0.05). At rs1799987, GG genotype
      was compared with AA genotype, and AG genotype was compared with AA genotype; the
      results showed that the renal damage due to HCV-related cryoglobulinemia was not
      decreased [odds ratio (OR) = 0.91, 95% confidence interval (95% CI): 0.47-1.54;
      OR = 0.89, 95% CI: 0.49-1.31]. The negative analysis model of the GG genotype
      reduced the risk of renal damage due to HCV-related cryoglobulinemia remarkably
      (OR = 0.62, 95% CI: 0.39-0.98). Rs1799987A/G and gene polymorphism of CCR5 may be
      associated with renal damage due to HCV-related cryoglobulinemia, and the
      carriage of G allele may lower the incidence rate of the disease, while
      rs35829419A/C in NLRP3 has no correlation with renal damage due to HCV-related
      cryoglobulinemia.

PMID- 30214526
TI  - Masquelet induced membrane technique for treatment of rat chronic osteomyelitis.
AB  - The application value of Masquelet induced membrane technique for the treatment
      of rat chronic osteomyelitis was explored. A total of 180 male Sprague-Dawley
      (SD) rats were randomly divided into sham operation group (control group),
      chronic osteomyelitis model group (model group) and Masquelet induced membrane
      therapy + chronic osteomyelitis model group (observation group); 60 rats in each
      group. A rat model of traumatic osteomyelitis was established using a modified
      blunt trauma method in model and observation group. All rats in observation group
      were treated with membrane induction technology while in the control group they
      were not. Postoperative complications, bone healing time and functional status of
      the affected limbs were recorded. After surgery, no obvious perioperative
      complications occurred in most of the rats, except that 5 rats experienced
      partial necrosis at the edge of the flap, and 3 experienced superficial infection
      around the incision site in the ilium. Primary bone healing was achieved in 50
      rats with an average healing time of 15 weeks. Among them, 38 rats restored
      weight-bearing function after 20 weeks. Seven rats experienced infection after
      surgery, but complete bone healing was achieved after treatment with induced
      membrane technique again. Following treatment with induced membrane technique,
      the rat body weight, body temperature and the number of bacteria in the wound
      decreased over time. In conclusion, Masquelet induced membrane technique is
      effective for the treatment of large bone defects in rats after traumatic
      osteomyelitis. This technique significantly shortens the treatment cycle. The
      surgical procedure is simple, and the incidence of postoperative complications is
      low.

PMID- 30214527
TI  - Values of serum LDL and PCT levels in evaluating the condition and prognosis of
      acute cerebral infarction.
AB  - Values of low density lipoprotein (LDL) and procalcitonin (PCT) levels in
      evaluating the condition and prognosis of patients with acute cerebral infarction
      (ACI) were investigated. According to the volume of cerebral infarction, 150
      patients with ACI (observation group) were divided into the mild infarction group
      (n=50), moderate infarction group (n=50), and severe infarction group (n=50).
      Besides, another 50 healthy subjects were enrolled during the same period as the
      control group. The levels of serum LDL and PCT on admission and at the 1st, 3rd,
      7th and 10th day after treatment were detected, which were compared with those in
      the control group. Ten days after treatment, patients were divided into two
      groups, the effective group and non-effective group, based on the clinical
      efficacy. The differences in LDL and PCT levels were compared between the two
      groups. After 1 month, the clinical efficacy was evaluated again, and the
      correlations of LDL and PCT levels with prognosis were analyzed. The levels of
      serum LDL and PCT in the observation group 1 day after admission were higher than
      those in the control group (P<0.05), which reached the peak at the 3rd day and
      continuously declined after the 7th day. The LDL and PCT levels had statistically
      significant differences between the effective group and non-effective group
      (P<0.05). Pearson's correlation analysis showed that the serum LDL and PCT levels
      in acute phase were negatively correlated with the National Institutes of Health
      Stroke Scale (NIHSS) score after 1 month of treatment (P<0.05). The dynamic
      monitoring of serum LDL and PCT levels in ACI patients can help evaluate the
      condition and prognosis of patients.

PMID- 30214529
TI  - An exploration on the influence of positive simple thyroid peroxidase antibody on
      female infertility.
AB  - The aim of the present study was to explore the influence of positive simple
      thyroid peroxidase antibody (TPO-Ab) on female infertility. Venous blood was
      collected on an empty stomach from infertile female patients (all of whom were in
      line with the World Health Organization's diagnostic criteria for infertility)
      receiving treatments at The Affiliated Wuxi Maternity and Child Health Care
      Hospital of Nanjing Medical University from 2014 to 2017 to detect thyroid
      function and thyroid antibodies [thyroglobulin antibody (TG-Ab), TPO-Ab and
      thyroid microsome antibody (TM-Ab)]. A total of 529 patients with normal thyroid
      function, TG-Ab and TM-Ab were included in the present study; they were divided
      into the positive group (121 cases with positive TPO-Ab) and the negative group
      (408 cases with negative TPO-Ab). Comparisons of age, body mass index (BMI),
      basal hormone levels, irregular menstruation, tubal obstruction, premature
      ovarian failure (POF), endometriosis (EMT) and polycystic ovary syndrome (PCOS)
      between the two groups of patients were conducted in order to determine whether
      the differences were statistically significant. The incidence rate of EMT was
      39.6% in the positive group and 17.1% in the negative group (P<0.05). The
      incidence rate of PCOS in the observation group was 43.9%, which was
      significantly higher than that of the control group (21.3%; P<0.01). The results
      revealed that the differences in age, BMI, basal hormone levels, irregular
      menstruation and POF between the two groups were not statistically significant
      (P>0.05). Finally, the factors that had statistical significance (EMT and PCOS)
      were stratified by different age groups to compare the incidence rate of positive
      results among the different age groups, thus concluding which age group was
      influenced to a greater extent by TPO-Ab. The results indicated that positive TPO
      Ab may be associated with PCOS and EMT, though particularly with PCOS. Infertile
      PCOS patients aged 28-35 years old were influenced more by TPO-Ab than those in
      other age groups. Thus, it is recommended that thyroid autoantibodies are
      detected in infertile PCOS females aged 28-35 years old, and treatment should be
      administered as soon thereafter.

PMID- 30214528
TI  - Plasminogen activator inhibitor-1 serves an important role in radiation-induced
      pulmonary fibrosis.
AB  - Radiation-induced pulmonary fibrosis is a serious complication. Plasminogen
      activator inhibitor-1 (PAI-1) has been indicated to be a key factor in the
      progression of pulmonary fibrosis. In the present study, the effect of PAI-1
      deficiency on radiation-induced pulmonary fibrosis was analyzed. Wild-type (WT)
      and PAI-1-deficient (PAI-1-/-) mice were treated with thoracic irradiation of 15
      Gy to induce pulmonary fibrosis. Analyses of bronchoalveolar lavage (BAL) fluids
      were performed 0, 4, 12, 18, and 24 weeks after irradiation. The degree of
      pulmonary fibrosis was assessed according to the histology of lung tissues and
      hydroxyproline contents. The results demonstrated that the irradiation of WT mice
      increased PAI-1 expression in the lungs after 18 weeks and established lung
      fibrosis at 24 weeks. The number of total cells and transforming growth factor
      beta levels in BAL fluid were significantly lower at 24 weeks after irradiation
      in PAI-1-/- mice compared with WT mice. Furthermore, histological examination
      revealed that the extent of pulmonary fibrosis was attenuated in PAI-1-/- mice
      compared with that in WT mice. Hydroxyproline content was also significantly
      lower in PAI-1-/- mice compared with WT mice at 24 weeks after irradiation. In
      conclusion, PAI-1 serves an important role in the development of radiation
      induced pulmonary fibrosis and may represent a novel therapeutic target for
      pulmonary fibrosis.

PMID- 30214530
TI  - Effect of Wnt signaling pathway on pathogenesis and intervention of neuropathic
      pain.
AB  - Neuropathic pain (NP) is a common clinical chronic pain with very complex
      mechanisms. This study explored the function of activated Wnt signaling pathway
      in NP. A rat model of chronic constriction injury (CCI) was established.
      Different doses of IWP-2, a Wnt signal inhibitor, were intrathecally injected to
      observe the behavior indicators at different time-points, including the pain
      induced by mechanical stimulation and thermal stimulation. The mRNA and protein
      levels of Wnt-3a, Frizzled 4 and beta-catenin in lumbar (L) 4-6 dorsal root
      ganglion (DRG) of rats in each group, as well as synaptic plasticity-related
      molecules in DRG region of rats were detected by RT-PCR and western blotting,
      respectively. Compared with Sham group and Naive group, paw withdrawal thermal
      latency and paw withdrawal mechanical threshold were significantly decreased
      after CCI, while synaptic plasticity was increased (P<0.05). Besides, activation
      of Wnt/beta-catenin signaling pathway was observed in rats with CCI. We found
      that intrathecal injection of IWP-2 effectively relieved the pain behavior and
      reduced the synaptic plasticity in rats with neuropathic pain after CCI,
      suggesting that the inactivated Wnt/beta-catenin signaling pathway might be the
      major mechanism responsible for this effect. Our data demonstrated that
      intrathecal injection of IWP-2 ameliorated neuropathic pain in CCI rats by
      inhibiting the Wnt/beta-catenin pathway.

PMID- 30214531
TI  - Clinical efficacy of meniscus plasty under arthroscopy in middle-aged and elderly
      patients with meniscus injury.
AB  - Clinical efficacy of meniscal plasty and total meniscectomy under arthroscopy in
      treating middle-aged and elderly patients with meniscus injury were explored. One
      hundred and fifteen elderly patients with meniscal injuries treated in the First
      Peoples Hospital of Wujiang District Suzhou from May 2012 to October 2014 were
      retrospectively analyzed. They were randomly divided into meniscal plasty group
      (experimental group) and total meniscectomy group (control group). Length of
      stay, operation time and VAS between the two groups were compared. Knee function
      was evaluated before the surgery and at the final follow-up using IKDC 2000 and
      Lysholm score. The differences of postoperative clinical efficacy and
      complications in both groups were observed. Postoperative IKDC 2000 and Lysholm
      score in the experimental group were superior to those of control group
      (P<0.001). There was no significant difference in the relieving effect of knee
      pain between the two types of procedures (P>0.05). Shorter operation time was
      found in control than that of experimental group. We did not observe remarkable
      differences in length of stay and postoperative complication rate between the two
      groups (P>0.05). Both meniscal plasty and total meniscectomy under arthroscopy
      can effectively relieve knee pain in a short time. Meniscal plasty could
      remarkably alleviate the progression of knee osteoarthritis, maintain knee
      function and improve daily life of affected population. We considered that
      meniscal plasty should be served as the preferred approach in treating middle
      aged and elderly patients with meniscus injury.

PMID- 30214532
TI  - Bacterial distribution, changes of drug susceptibility and clinical
      characteristics in patients with diabetic foot infection.
AB  - The present study aimed to investigate the bacterial distribution, changes in
      drug susceptibility and clinical characteristics in patients with diabetic foot
      infection (DFI). A retrospective analysis of 216 patients with DFI treated at
      Xinxiang Central Hospital between 2013 and 2016 was carried out to analyze the
      bacterial distribution, changes of susceptibility and clinical characteristics. A
      total of 262 pathogenic strains were isolated from 216 patients with DFI. Among
      them, 43.13% exhibited Gram-positive (G+) bacteria, 45.04% exhibited Gram
      negative (G-) bacteria and 11.83% was other. Between 2013 and 2016, the
      susceptibility of pathogenic bacteria to common antibacterial drugs showed a
      declining trend year by year. G+ bacteria had high susceptibility to vancomycin
      and acetazolamide; while G- bacteria showed high susceptibility to dibekacin,
      panipenem and biapenem. The main clinical symptoms of the 216 patients included
      edema (98.61%), purulent secretions (62.96%) and lower extremity sepsis (58.80%).
      The top three complications of the 216 cases were lower extremity vascular
      disease (58.80%), peripheral neuropathy (39.81%) and kidney disease (26.39%).
      Logistic regression analysis showed that age [odds ratio (OR), 2.708; P=0.005],
      previous use of antibacterial drugs (OR, 3.816; P=0.007) and application of the
      third generation cephalosporins (OR, 3.014; P=0.008) were the independent risk
      factors of drug resistance in patients with DFI (P<0.05). There were numerous
      types of pathogens in patients with DFI, and all of them had certain drug
      resistance. The drug susceptibility was decreasing year by year. The pathogens
      and drug resistance in patients with DFI should be monitored to reduce the
      incidence of related complications and improve the prognosis of patients.

PMID- 30214533
TI  - Analysis of gene expression and functional changes of adrenal gland in a rat
      model of kidney yang deficiency syndrome treated with Sini decoction.
AB  - Sini decoction (SND), a well-known traditional Chinese medicine, has been used to
      treat kidney Yang deficiency for ~1,800 years. The present study aimed to
      evaluate the effects of SND treatment on hypothalamic-pituitary-adrenal axis
      hormones in a rat model of Yang deficiency and to explore the molecular
      mechanisms using microarray analysis of adrenal glands and in vitro
      adrenocortical cell culture systems. The results indicated that SND treatment
      recovered circulating serum cortisol, adrenocortical hormone (ACTH) and
      testosterone levels in a yang deficiency model. Immunohistochemical analysis of
      pituitary and hypothalamic tissues confirmed increased expression of ACTH and
      corticotropin-releasing factor, respectively, in response to SND treatment.
      Microarray analysis identified a marked upregulation of genes involved in
      <=metabolic and stress response pathways in rat adrenal tissues in response to
      SND treatment, exemplified by cyclooxygenase-2 and nuclear factor (NF)-kappaB. In
      vitro, SND exerted a protective effect on mitochondria in response to H2O2
      exposure also activated NF-kappaB and cyclic adenosine monophosphate response
      element binding protein reporter gene activity. These results contributed towards
      an improved understanding of how SND effectively alleviates the symptoms of
      kidney Yang deficiency syndrome at the molecular level.

PMID- 30214534
TI  - Sedated gastroscopy improves detection of gastric polyps.
AB  - The detection rate of gastric polyps (GPs) is low, improving the detection rate
      would be good. The present study aimed to evaluate the role of sedated
      gastroscopy in GP detection. The data of patients who underwent gastroscopic
      examination from January 2014 to December 2016 at the First Affiliated Hospital
      of Wenzhou Medical University (Wenzhou, China) were retrospectively reviewed.
      Endoscopic records of 6,195 patients diagnosed with GPs were analyzed. The GP
      detection rate was 3.12 and 5.11% in the unsedated and sedated gastroscopy group,
      respectively (P<0.05). Also after stratification by sex, the GP detection rate
      was significantly higher in the sedated gastroscopy group (P<0.05). In addition,
      patients aged >=20 years in the sedated gastroscopy group had a higher GP
      detection rate than those in the unsedated gastroscopy group (P<0.05). The
      incidence of cardiac, gastric fundus, gastric body and multiple-site GPs was
      significantly different between the two groups (P<0.05). GPs <=0.5 and >0.5 cm
      were more common in the sedated gastroscopy group than in the unsedated
      gastroscopy group (P<0.05). The common pathologic types of GPs were gastric
      fundus gland (52.27%) and hyperplastic polyps (34.74%). In conclusion, the GP
      detection rate may be improved by inhibition of gastric muscle cramping with
      sedation.

PMID- 30214535
TI  - Sitagliptin reduces insulin resistance and improves rat liver steatosis via the
      SIRT1/AMPKalpha pathway.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. It is
      asymptomatic at presentation and is frequently identified among individuals with
      metabolic dysfunction, including obesity and diabetes. NAFLD is primarily
      characterized by the accumulation of triacylglycerol in the liver. Since insulin
      resistance and fat metabolism dysregulation are major causes of type 2 diabetes
      and NAFLD, anti-diabetes agents are widely considered as potential therapy
      strategies for NAFLD. Sitagliptin, an inhibitor of dipeptidyl peptidase-4, has
      been developed as an oral anti-hyperglycemic agent. In the present study, the
      effect of sitagliptin on the progression of NAFLD was evaluated in a rat model
      fed with a high fat diet (HFD). It was identified that sitagliptin significantly
      suppressed lipid accumulation in rat blood and liver and improved insulin
      resistance. Furthermore, it was revealed that sitagliptin reactivated the HFD
      suppressed SIRT1/AMPK axis pathway and upregulated its downstream target genes,
      modulating fatty acid metabolism. These findings demonstrate a preventive effect
      of sitagliptin on hepatic lipid dysregulation and suggest that sitagliptin has
      potential as a clinical therapeutic strategy for NAFLD.

PMID- 30214536
TI  - Association of OGG1 and DLST promoter methylation with Alzheimer's disease in
      Xinjiang population.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder leading to progressive
      memory and cognitive impairment. Previous studies have identified multiple genes
      associated with AD. The aim of the present study was to validate the association
      of the five AD-associated variants, 8-oxoguanine DNA glycosylase 1 (OGG1)
      rs1052133, bridging integrator 1 rs744373, sortilin-related receptor 1,
      rs1133174, presenilin 2 rs8383, and nerve growth factor rs6330, in the Xinjiang
      Chinese population. In addition, the present study evaluated the contribution of
      the promoter methylation of two genes, OGG1 and dihydrolipoamide
      succinyltransferase (DLST) to the risk of AD. A total of 17 AD cases and 34
      controls were recruited from Xinjiang province in China. Genotyping was done by
      Sanger sequencing. DNA methylation assay was performed using quantitative
      methylation specific polymerase chain reaction. The study was unable to repeat
      the previous association of the five genetic polymorphisms with AD. However, DLST
      methylation levels were demonstrated to be significantly decreased in AD patients
      (P=0.027), particularly in female AD patients (P=0.025). Subgroup analysis by
      apolipoprotein E (APOE epsilon4) genotype demonstrated that OGG1 methylation
      levels were significantly increased in APOE non-epsilon4 carriers compared with
      APOE epsilon4 carriers (P=0.027). In summary, the present study reported that
      DLST hypomethylation was significantly associated with AD in females, and that
      OGG1 promoter methylation may interact with APOE epsilon4 genotype.

PMID- 30214537
TI  - Radioprotective effect of lactoferrin in mice exposed to sublethal X-ray
      irradiation.
AB  - The radioprotective effect of lactoferrin (LF) was studied in mice subjected to
      sublethal X-ray irradiation. The mice were randomly divided into the Control (non
      irradiated mice fed a standard diet without LF), IR (irradiated mice fed a
      standard diet) and IR+LF (irradiated mice fed LF) groups. The mice were fed daily
      for 7 days prior to irradiation and for 30 continuous days following irradiation.
      The survival ratio of the mice in the IR+LF group was significantly increased
      compared with the IR group between days 15 and 30 after irradiation. The body
      weight of the mice in the IR+LF group was increased compared with the IR group,
      and the difference was statistically significant. Blood was collected from the
      mice via the tail vein on days 2, 7, 14, 21 and 30 following irradiation. The
      laboratory indicators, including leukocyte, erythrocyte and platelet counts
      recovered more rapidly following irradiation in the IR+LF group compared with the
      IR group. Treatment of the irradiated mice with LF significantly reduced the DNA
      damage. In the hepatic tissue the level of superoxide dismutase in the IR+LF
      group was significantly increased, while malondialdehyde was significantly
      decreased compared with the IR group. These findings indicate that LF may prevent
      radiation damage and may have potential as a treatment for patients with cancer
      who receive radiotherapy.

PMID- 30214538
TI  - Evaluation of the diagnostic value of the immunoblotting and ELISA tests using
      recombinant Em18 antigen in human alveolar echinococcosis from Xingjiang China.
AB  - Alveolar echinococcosis (AE) is a prevalent epidemic in the northern hemisphere,
      especially in central Europe and western China. Serum diagnosis is important for
      patients with AE, especially during the first screening. The present study
      purified the recombinant Em18-GST (rEm18-GST), and detected its diagnostic
      performance in human alveolar echinococcosis patients of Xinjiang, China with
      immunoblotting (IB) and enzyme-linked immunosorbent assay (ELISA). Serum samples
      were collected from 50 patients with AE, 222 patients with cystic echinococcosis
      (CE), 158 patients with other unrelated infections and 106 healthy individuals.
      The IB results showed that serum samples of 47 patients with AE and 12 patients
      with CE were rEm18-positive. However, only one sample from patients with cancer
      showed a cross-reaction with rEm18 in IB. The overall sensitivity was 94%, and
      the total specificity was 96.58%. For the rEm18 results using ELISA, the sera of
      46 patients with AE were positive, and the overall sensitivity was 92%. In
      conclusion, compared with imaging tools, including computed tomography, magnetic
      resonance imaging and positron emission tomography, rEm18 has considerable
      advantages for AE serodiagnosis.

PMID- 30214539
TI  - Characteristics of bone marrow cells in 107 patients with juvenile idiopathic
      arthritis: A retrospective study.
AB  - Few studies to date have reported on the myelodysplastic features of children
      with juvenile idiopathic arthritis (JIA). Bone marrow specimens were collected
      from 107 patients aged from 7-12 years who were initially diagnosed with JIA
      between May 2013 and October 2015. In 107 patients with JIA, bone marrow
      proliferation was higher than normal and hemophagocytes were more easily observed
      than usual. The characteristics of bone marrow cells in 107 patients with JIA
      were investigated and the associations of these characteristics with the disease
      was discussed in the present study. It was noticed that there were similar
      changes in the myeloid, erythropoietic and megakaryopoietic series in the
      majority of bone marrow specimens; the presence of hemophagocytes was also
      reported. The present findings suggest that JIA is associated with specific
      myelodysplastic changes, and that cellular immune system dysfunction and
      overreactive inflammatory cytokines may contribute to the development of these
      myelodysplastic changes in the bone marrow.

PMID- 30214540
TI  - Menaquinone-4 modulates the expression levels of calcification-associated factors
      to inhibit calcification of rat aortic vascular smooth muscle cells in a dose
      dependent manner.
AB  - Vascular calcification (VC) caused by chronic kidney disease (CKD)-mineral and
      bone disorder is a common complication of CKD. Recent studies have demonstrated
      that menaquinone-4 (MK-4) is negativly associated with VC in patients with CKD.
      Furthermore, we have previously shown that runt-related transcription factor 2
      (Runx2) is important in the phenotypic transformation process of rat vascular
      smooth muscle cells (VSMCs), which is the key step for the development of VC. The
      present study investigated the influence of MK-4 on the phenotypic transformation
      process of rat VSMCs in order to illustrate its role in the process of VC.
      Calcification assays were perfomed to access the calcified degree of rat VSMCs.
      Additionally, the genes and proteins related to phenotypic transformation were
      measured by reverse transcription-polymerase chain reaction and western blotting
      methods. It was revealed that calcium deposition in the cells was evidently
      increased with an addition of beta-glycerophosphate (beta-GP) and could be
      completely prevented by co-incubation with MK-4 in a dose-dependent manner.
      Furthermore, the expression of Runx2 in the beta-GP-induced VSMCs was inhibited
      by MK-4. It was also revealed that the expression of SMAD1 and bone morphogenetic
      protein (BMP)-2 were decreased in the beta-GP-induced VSMCs treated with MK-4 in
      a dose-dependent manner; however, the expression of SMAD7 was increased in the
      beta-GP-induced VSMCs treated with MK-4 in a dose-dependent manner. These
      observations suggest that MK-4 reduces mineralization by regulating the BMP-2
      signaling pathway in order to attenuate the expression of Runx2.

PMID- 30214541
TI  - Congenital anomalies in infants conceived by infertile women through assisted
      reproductive technology: A cohort study 2004-2014.
AB  - This retrospective cohort study aimed to analyse the risk of congenital anomalies
      (CAs) in infants conceived by infertile women through assisted reproductive
      technology (ART). A total of 9,013 clinical pregnancy cycles resulting in 9,101
      live births between 2004 and 2014 were analysed. Congenital anomalies were
      evaluated and compared with spontaneous pregnancies in infertile women. A total
      of 9,101 infants were born following ART. Three subgroups were established: In
      vitro fertilisation fresh embryo transfer (IVF-ET), n=2,919, intracytoplasmic
      sperm injection fresh embryo transfer (ICSI), n=1,996 and frozen-thawed embryo
      transfer (FET), n=4,186. No significant differences in perinatal outcomes were
      observed between the three subgroups. A total of 105 (1.15%) infants were born
      with CAs. The birth defect rate was slightly higher in the IVF-ET subgroup
      compared with the other subgroups. Among infants in the IVF-ET and ICSI-ET
      subgroup, the probability of birth defects increased with increased maternal age
      (>35 years), male factors and diminished ovarian reserve. In the FET group, the
      risk of birth defects was significantly increased with multiple births and
      maternal age >35 years. The risk of congenital anomalies following ART was not
      significantly different compared with spontaneous conceptions within the
      infertile study population. The results of the present study may provide guidance
      for patients who are considering treatment for infertility in China.

PMID- 30214542
TI  - Effect of luteolin on the methylation status of the OPCML gene and cell growth in
      breast cancer cells.
AB  - The present study aimed to investigate the effect of luteolin on the methylation
      of opioid binding protein/cell adhesion molecule (OPCML) in breast cancer cells,
      as well as its underlying mechanism of action. Human breast cancer cell lines
      BT474 and MCF-7 were cultured in RPMI-1640 medium supplemented with 10% fetal
      bovine serum. The cells were treated with 0-30 umol/l luteolin prior to
      investigation. Reverse transcription-quantitative polymerase chain reaction and
      western blot analysis were used to determine the mRNA and protein expression,
      respectively. High performance liquid chromatography and electrosprary ionization
      mass spectrometry was used to analyze the methylation of the OPCML promoter
      region and whole genome. The methylation activity in the cell nucleus was
      determined using a DNA methyltransferase catalytic test. ELISA analysis was used
      to detect changes in the activity of transcription factors Sp1 and nuclear factor
      (NF)-kappaB. An MTT assay was performed to determine cell proliferation, while
      flow cytometry was used to detect cell cycle stage and apoptosis. Luteolin
      effectively upregulated the expression of OPCML in breast cancer cells. Luteolin
      activated OPCML by reducing intracellular methylation levels. Luteolin
      downregulated intracellular methylation levels by decreasing Sp1 and NF-kappaB
      activities. Luteolin affected the expression of DNMT1 and OPCML by downregulating
      Sp1 activity. Luteolin inhibited the proliferation and induced the apoptosis of
      BT474 and MCF-7 cells. The results of the present study suggest that luteolin
      inhibits the growth of breast cancer cells by decreasing the methylation and
      upregulating the expression of the OPCML gene.

PMID- 30214543
TI  - Longitudinal behavioral and fMRI-based assessment of inhibitory control in heroin
      addicts on methadone maintenance treatment.
AB  - The objective of the present study was to determine whether methadone maintenance
      treatment (MMT) in heroin-dependent patients affects inhibitory control, whether
      any MMT-induced changes correlate with methadone dose and MMT duration, and
      whether these changes depend on the psychological characteristics of patients,
      such as depression, anxiety and impulsivity. Response inhibition in the GO/NO-GO
      test was combined with functional magnetic resonance imaging (fMRI) scanning data
      to examine whether MMT affects inhibitory control in 21 heroin-addicted patients
      who had already undergone at least three months of MMT. Patients were evaluated
      one year prior to and after the MMT period. Participants exhibited no difference
      in their GO/NO-GO reaction time and accuracy rate, or in their false alarm rate
      under NO-GO conditions. However, increased activation was detected in numerous
      brain regions in their 12-month fMRI scans, although these were not in the
      frontal-striatal loop. Increased fMRI activation in the left precentral gyrus and
      superior temporal gyrus were negatively correlated with the daily methadone dose
      and total methadone dose during the one-year study period. In conclusion, these
      results suggested that MMT over one year does not significantly change the
      behavioral indicators of inhibitory control function in heroin-dependent
      patients. The increase in activation leads to the hypothesis that MMT over one
      year may increase cognitive inhibitory control, which may be the result of the
      combined negative effect of methadone and the positive effect of functional
      recovery after withdrawal of heroin.

PMID- 30214545
TI  - Hsa_circ_0033155: A potential novel biomarker for non-small cell lung cancer.
AB  - Circular RNAs (circRNAs) are a novel type of endogenous RNAs and increasing
      evidence have uncovered the important role of circRNA in tumor progression;
      however, the function of circRNAs in non-small cell lung cancer (NSCLC) remains
      largely unclear. In the present study, it was demonstrated that the expression
      level of hsa_circ_0033155 was significantly downregulated in NSCLC tissue and the
      expression of hsa_circ_0033155 correlated with lymphatic metastasis. In order to
      further investigate the possible role of hsa_circ_0033155 in NSCLC progression,
      circRNA was overexpressed in NSCLC cells and it was observed that the
      overexpression of hsa_circ_0033155 significantly decreased cell proliferation,
      colony formation and migration, and elevated the level of phosphatase and tensin
      homolog deleted on chromosome 10, a tumor suppressor in many types of tumor. In
      conclusion, hsa_circ_0033155 may serve as a prospective biomarker for detection
      and a promising therapeutic target for NSCLC.

PMID- 30214544
TI  - Regulation of mPGES-1 composition and cell growth via the MAPK signaling pathway
      in jurkat cells.
AB  - Previous studies have suggested that microsomal prostaglandin E synthase-1 (mPGES
      1) is highly expressed and closely associated with mitogen-activated protein
      kinase (MAPK) signaling pathways in various types of malignant cells. However,
      their expression patterns and function with respect to T-cell acute lymphoblastic
      leukemia (T-ALL) remain largely unknown. The present study investigated whether
      mPGES-1 served a crucial role in T-ALL and aimed to identify interactions between
      mPGES-1 and the MAPK signaling pathway in T-ALL. The results indicated that mPGES
      1 overexpression in T-ALL jurkat cells was significantly decreased by RNA
      silencing. Decreasing mPGES-1 on a consistent basis may inhibit cell
      proliferation, induce apoptosis and arrest the cell cycle in T-ALL jurkat cells.
      Microarray and western blot analyses revealed that c-Jun N-terminal kinase served
      a role in the mPGES-1/prostaglandin E2/EP4/MAPK positive feedback loops. In
      addition, P38 and extracellular signal-regulated kinase 1/2 exhibited negative
      feedback effects on mPGES-1. In conclusion, the results suggested that cross-talk
      between mPGES-1 and the MAPK signaling pathway was very complex. Therefore, the
      combined regulation of mPGES-1 and the MAPK signaling pathway may be developed
      into a new candidate therapy for T-ALL in the future.

PMID- 30214546
TI  - Resveratrol ameliorates sepsis-induced acute kidney injury in a pediatric rat
      model via Nrf2 signaling pathway.
AB  - Acute kidney injury (AKI) is a hyper-inflammation-induced abrupt loss of kidney
      function and has become a major public health problem. The cecal ligation and
      puncture (CLP) model of peritonitis in rat pups mimics the development of sepsis
      induced pediatric AKI is pre-renal without morphological changes of the kidneys
      and high lethality. Resveratrol, a natural polyphenolic compound with low
      toxicity, has obvious anti-oxidant and anti-inflammatory properties. The present
      study aimed to determine whether resveratrol alleviates pediatric AKI and
      investigated the potential mechanism. Thus, a CLP model of 17-18 day-old rat pups
      was used to mimic the development of sepsis-induced AKI in children. In the group
      treated with resveratrol, renal injury induced by CLP was alleviated with
      downregulation of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and
      kidney injury molecule (KIM)-1 expression. Nuclear factor-erythroid-2-related
      factor 2 (Nrf2) signaling is known to effectively inhibit inflammation, the
      present study found that resveratrol reduced the lipopolysaccharide-induced
      inflammatory response in kidney cells in vitro and induced the activation of Nrf2
      signaling, including accumulation of nuclear Nrf2 and increase of the expression
      of Nrf2 target genes heme oxygenase (HO)-1 and NAD(P)H dehydrogenase (quinone) 1
      (NQO1); this was confirmed by the induction of the expression of HO-1 and NQO1 by
      treatment of resveratrol in vitro and in vivo. Of note, knockdown of Nrf2
      effectively abrogated the downregulation of TNF-alpha, IL-1beta and KIM-1
      expression induced by resveratrol in vitro. These results suggested that
      resveratrol ameliorates sepsis-induced acute kidney injury in a pediatric model
      of AKI via the Nrf2 signaling pathway.

PMID- 30214547
TI  - Oscillatory positive expiratory pressure treatment in lower respiratory tract
      infection.
AB  - Oscillatory positive expiratory pressure (OPEP) devices have been utilized as an
      adjunct therapy to conventional chest physiotherapy (CPT) to promote the
      clearance of respiratory secretions in individuals with impaired ability to
      cough, particularly in chronic diseases. However, few studies have focused on the
      effectiveness of OPEP in lower respiratory tract infection. In the present study,
      all patients with lower respiratory tract infections hospitalized in the
      Department of Pulmonary and Critical Care Medicine, Ruijin Hospital (Shanghai,
      China) between February 2016 and July 2017 were analyzed. Daily sputum quantity
      and purulence were recorded on the first 7 days of physiotherapy. Oxygenation
      index, partial pressure carbon dioxide, white blood cell count, neutrophil
      percentage, C reactive protein (CRP) and procalcitonin (PCT) levels before and
      after CPT were compared between patients who received OPEP and patients who
      received mechanical percussion (MP). Sputum was collected prior to and following
      CPT. A total of 17 patients received OPEP, while 10 received MP. The OPEP group
      exhibited improved postural drainage compared with the MP group after 7 days of
      physiotherapy. After 7 days of CPT, patients who received OPEP also exhibited a
      significantly improved oxygenation index, while the oxygenation index in the MP
      group did not improve. The improvement of partial pressure carbon dioxide was not
      significantly different between groups. The OPEP group also exhibited a greater
      decrease in white blood cell count, neutrophil percentage and CRP levels,
      compared with the MP group. However, the decrease in PCT level was similar in the
      OPEP and MP groups. Sputum culture results revealed that the rate of negative
      conversion was very low in both groups. There was no difference between the two
      groups in terms of hospitalization outcomes. In conclusion, OPEP exhibited a
      greater effectiveness in draining sputum, improving oxygenation and reducing
      inflammatory status in patients with lower respiratory tract infections compared
      with MP; however, it did not promote the elimination of microbes.

PMID- 30214548
TI  - MicroRNA-6852 suppresses cell proliferation and invasion via targeting forkhead
      box J1 in gastric cancer.
AB  - Accumulating evidence suggests that microRNAs (miRs) exert vital functions in the
      development and progression of multiple types of human cancer. However, the role
      of miR-6852 in gastric cancer (GC) remains unclear. In the present study, miR
      6852 expression was significantly downregulated in GC tissues compared with
      adjacent normal tissues determined by reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) analysis. Furthermore, miR-6852 expression
      levels in patients with GC were reversely correlated with tumor metastasis and
      TNM stage. Through Cell Counting kit-8 and Transwell assays, it was demonstrated
      that overexpression of miR-6852 significantly inhibited the proliferation,
      migration and invasion of GC cells. With regards to the mechanism involved,
      luciferase reporter assays suggested that miR-6852 directly target forkhead box
      J1 (FOXJ1) in GC cells. Furthermore, overexpression of miR-6852 markedly
      inhibited the mRNA and protein expression levels of FOXJ1 in GC cells determined
      by RT-qPCR and western blot analysis. Additionally, FOXJ1 was overexpressed in GC
      tissues and cell lines, and its expression was negatively correlated with that of
      miR-6852 in GC tissues. Rescue assays indicated that overexpression of FOXJ1
      significantly reversed the effects of miR-6852 transfection on GC cell
      proliferation, migration and invasion. Taken together, the present findings
      demonstrated that miR-6852 exerted a tumor suppressive role through targeting
      FOXJ1 in GC. These results implied that miR-6852 may be a novel therapeutic
      target of GC treatment.

PMID- 30214549
TI  - Identification of a missense mutation in MIP gene via mutation analysis of a
      Guangxi Zhuang ethnic pedigree with congenital nuclear cataracts.
AB  - At present, congenital cataract is the world's leading cause of blindness among
      children. The aim of the present study was to determine and analyze the genetic
      disorder associated with a congenital nuclear cataract in a three-generation
      family of Guangxi Zhuang ethnicity. A total of 3 affected individuals and 5
      unaffected family members underwent appropriate comprehensive medical
      examinations, mainly of the eyes. The white blood cells of the family members
      were collected and genomic DNA was extracted from 100 healthy individuals, as the
      control group. The sequences of candidate genes were determined by polymerase
      chain reaction amplification followed by direct sequencing. The functional
      consequences of the mutation were analysed with biology software. A missense
      mutation (c.97C>T) was found in exon 1 of major intrinsic protein of lens fiber
      (MIP) gene. Therefore, the arginine of the highly conserved codon 33 was changed
      to cysteine. This mutation was identified in the affected family members, but not
      identified in unaffected family members or the 100 normal controls. The mutation
      in the MIP gene is the genetic cause of the congenital cataract in the ethnic
      Guangxi Zhuang family.

PMID- 30214550
TI  - Erratum: Expression and association of VEGF-Notch pathways in infantile
      hemangiomas.
AB  - [This corrects the article DOI: 10.3892/etm.2017.4943.].

PMID- 30214551
TI  - Present and future of cancer immunotherapy: A tumor microenvironmental
      perspective.
AB  - Modulation of the tumor microenvironment is becoming an increasingly popular
      research topic in the field of immunotherapy, and studies regarding immune
      checkpoint blockades and cancer immunotherapy have pushed cancer immunotherapy to
      a climax. Simultaneously, the manipulation of the immune regulatory pathway can
      create an effective immunotherapy strategy; however, the tumor microenvironment
      serves an important role in suppressing the antitumor immunity by its significant
      heterogeneity. A number of patients with cancer do not have a good response to
      monotherapy approaches; therefore, combination strategies are required to achieve
      optimal therapeutic benefits. Targeting the tumor microenvironment may provide a
      novel strategy for immunotherapy, break down the resistance of conventional
      cancer therapy and produce the foundation for personalized precision medicine.
      The present review summarized the research regarding cancer immunotherapy from
      the perspective of how the tumor microenvironment affects the immune response,
      with the aim of proposing a novel strategy for cancer immunotherapy and
      combination therapy.

PMID- 30214552
TI  - Quantitative 18F-FDG PET analysis in survival rate prediction of patients with
      non-small cell lung cancer.
AB  - The aim of the present study was to investigate the prognostic value of
      quantitative [18F]fluorodeoxyglucose (FDG) positron emission tomography
      (PET)/computed tomography (CT) parameters for patients with non-small cell lung
      cancer (NSCLC). The present study conducted a retrospective review of the medical
      records of 203 patients with NSCLC, of which 193 patients underwent baseline 18F
      FDG PET/CT prior to initial therapy. Multivariate analyses using Cox's
      proportional hazards regression were performed for the assessment of the
      association between initial PET/CT measurements and overall survival (OS). The
      multivariate models were adjusted for sex, age, smoking status, disease stage,
      standardized uptake value (SUV), standardized uptake value corrected for lean
      body mass (SUL), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and
      standard deviation of SUV (SD). Kaplan-Meier (K-M) estimator curves were
      constructed following the formation of three approximately equal-sized groups
      using tertiles for each PET/CT measurement (n=65, 64 and 64). OS curves were
      plotted using K-M estimator curves. Results demonstrated significant associations
      between OS and MTVPET volume computerized assisted reporting (PETVCAR), MTV2.5,
      MTV25%, MTV42% and TLGPETVCAR; however, no significant associations were
      identified between OS and MTV50%, MTV75%, TLG2.5, all SUV and SUL. Subgroup
      analyses according to pathology demonstrated that there were statistically
      significant associations between OS and stage (P<0.001), MTV50% (P=0.002) and
      MTV42% (P=0.004) in the adenocarcinoma group, and SULmean (P=0.010), MTV25%
      (P=0.005) and MTV42% (P=0.001) in the squamous cell carcinoma group; however, no
      significant differences were identified between any other group. Furthermore,
      there was a significant association between OS and MTV42% (P=0.02) and MTV50%
      (P=0.04) in the early-stage group; however, no significant differences were
      identified in the advanced-stage group. K-M estimator curve analyses demonstrated
      that the pathology (P=0.01), stage (P<0.001) and all PET metabolic parameters
      with the exception of SD were significantly associated with OS (P<0.05). No
      significant associations were demonstrated between SD and OS. In conclusion, 18F
      FDG PET/CT MTVPETVCAR, MTV2.5, MTV25%, MTV42% and TLGPETVCAR exhibit prognostic
      values with regard to OS. Overall, selection of appropriate metabolic parameters
      may predict NSCLC prognosis.

PMID- 30214553
TI  - Promyelocytic leukemia zinc finger triggers ATP-binding cassette subfamily E
      member 1-mediated growth inhibition in breast cancer cells.
AB  - The promyelocytic leukemia zinc finger (PLZF) protein is a transcription factor
      that is involved in a number of biological processes, including those regulating
      cellular growth; however, little is known regarding how it achieves its
      inhibitory effect in different cell and tissue types. It has previously been
      demonstrated that PLZF expression levels become diminished during the oncogenic
      transformation of certain tissue types and thus, may serve as a hallmark for
      tumor aggressiveness. To examine this in breast cancer, survival curves from
      available oncology databases were analyzed and demonstrated that PLZF expression
      was positively associated with increased survival in patients with breast cancer.
      The mRNA and protein levels of PLZF were also revealed to be associated with the
      tumorigenicity of four breast cancer cell lines. Since ATP-binding cassette
      subfamily E member 1 (ABCE1), also known as RNase L inhibitor, has been
      determined to be a target gene of PLZF, the present study also investigated
      whether the tumor suppressive effect of PLZF was associated with ABCE1
      expression. PLZF was revealed to downregulate the expression of ABCE1 in vitro,
      which relieved the inhibitory effect of ABCE1 on the ribonuclease L enzyme.
      Finally, it was concluded that PLZF expression caused an ABCE1-mediated increase
      in cellular cytotoxicity, as demonstrated by a reduction in the proliferation
      rate of breast cancer cell lines. The results of the present study are important
      for understanding how PLZF exerts its final inhibitory actions in breast cancer
      cells, and potentially in other solid tumors, through the modulation of
      immunological pathways.

PMID- 30214554
TI  - 18F-FDG PET/CT for the early prediction of the response rate and survival of
      patients with recurrent or metastatic breast cancer.
AB  - The present study aimed to explore the value of fludeoxyglucose F 18 positron
      emission tomography-computed tomography (PET/CT) for the early prediction of
      chemotherapy remission rates and survival in patients with recurrent and
      metastatic breast cancer. A total of 24 patients diagnosed with recurrent or
      metastatic breast cancer between 2009 and 2014 were enrolled. All patients
      underwent a PET/CT examination prior to (PET/CT1) and following (PET/CT2)
      chemotherapy. Differences of PET/CT1 maximal standardized uptake values (SUVmax),
      PET/CT2 SUVmax, DeltaSUVmax and the DeltaSUVmax% between objective remission (OR)
      and non-OR groups were measured. Survival differences between OR and non-OR
      groups and the overall survival (OS) between metabolic responsive and metabolic
      non-responsive groups were analyzed. In the present study, it was revealed that
      DeltaSUVmax and DeltaSUVmax% were significantly higher in the OR group compared
      with the non-OR group (P<0.001). Overall survival was significantly prolonged in
      the OR and metabolic responder groups compared with their respective control
      groups (P<0.001 and P<0.01, respectively). DeltaSUVmax% were significantly
      positively associated with OS (r2=0.266; P<0.01). In conclusion, PET/CT may be
      valuable for the early prediction of the chemotherapy efficacy and survival of
      patients with recurrent or metastatic breast cancer.

PMID- 30214555
TI  - A TOP2A-derived cancer panel drives cancer progression in papillary renal cell
      carcinoma.
AB  - The aim of the present study was to investigate the function of the DNA
      topoisomerase IIalpha (TOP2A) gene and its associated genes in the progression of
      papillary renal cell carcinoma (PRCC). Online cancer databases, including
      cBioportal, Oncomine, OncoLnc and Search Tool for the Retrieval of Interacting
      Genes/Proteins were used to analyze the TOP2A gene expression profile, function
      and regulation network in PRCC. The genes that were significantly co-expressed or
      mutually exclusively expressed with TOP2A were identified. The genes co-expressed
      with TOP2A were defined as a 'TOP2A-cancer panel', which cooperatively promotes
      PRCC progression. This gene panel performed well in predicting the prognosis of
      PRCC. In addition, the TOP2A-cancer panel significantly affected the outcome of
      PRCC compared with clear cell renal cell carcinoma (CCRCC). The protein-protein
      interaction network of all genes associated with TOP2A was also generated. This
      interaction network may provide foundation for the additional investigation of
      TOP2A. Integrative understating of the TOP2A-cancer panel may result in a novel
      avenue for treatment intervention in PRCC.

PMID- 30214557
TI  - Serum ProGRP and NSE levels predicting small cell lung cancer transformation in a
      patient with ALK rearrangement-positive non-small cell lung cancer: A case
      report.
AB  - The resistance mechanisms to anaplastic lymphoma kinase (ALK) inhibitors comprise
      ALK gene variations, such as ALK point mutations and copy-number gains, the
      activation of bypass signaling through the activation of other oncogenes and
      small cell lung cancer (SCLC) transformation. To date, few studies have
      investigated whether tumor markers for SCLC correlate with the SCLC
      transformation in EGFR-mutant NSCLC and ALK-positive non-SCLC (NSCLC). The
      present case study reported a patient with SCLC transformation after alectinib
      treatment. The patient exhibited elevation of pro-gastrin-releasing peptide
      precursor and neuron-specific enolase levels, which may be predictive of SCLC
      transformation during the resistance to ALK-tyrosine kinase inhibitors.

PMID- 30214556
TI  - Identification of RFC5 as a novel potential prognostic biomarker in lung cancer
      through bioinformatics analysis.
AB  - Lung cancer is the leading cause of mortalities among all types of cancer.
      Therefore, the screening of biomarkers that are related with the progression of
      lung cancer is crucial for early diagnosis and efficient therapy of lung cancer.
      In the present study, bioinformatic analysis identified replication factor C 5
      (RFC5) as a potential novel oncogene in lung cancer. RFC5 functions as a clamp
      loader and is involved in DNA replication and repair. Analysis of public
      databases and reverse transcription-quantitative polymerase chain reaction
      indicated that RFC5 was significantly increased in tumor tissues compared with
      adjacent normal tissues. A high RFC5 expression was observed to be associated
      with more aggressive malignant clinicopathological features, including higher T
      stage, more advanced regional lymph node metastasis and a higher probability of
      relapse. Notably, there were notable differences in overall survival (OS), first
      progression and post-progression survival between the high RFC5 expression group
      and low RFC5 expression group. Univariate and multivariate Cox regression
      analyses indicated that RFC5 was an independent risk factor that was associated
      with poorer OS and disease-free survival. According to GSEA, several gene sets
      that are associated with cell cycle and DNA damage were enriched in the RFC5
      overexpression group, which indicated that RFC5 might promote the proliferation
      of lung cancer cells. Our finding indicated that RFC5 might be a novel prognostic
      biomarker of lung cancer, and it might be serve as a potential diagnosis and
      therapy target for lung cancer in the future.

PMID- 30214558
TI  - Dihydromyricetin induces apoptosis in a human choriocarcinoma cell line.
AB  - Choriocarcinoma is a malignant trophoblastic tumor. The development of novel
      drugs is required to reduce the toxicity of current multi-agent chemotherapy and
      to successfully treat chemoresistant cases of the disease. The purpose of the
      present study was to investigate the effect of dihydromyricetin (DMY) on the
      human choriocarcinoma cell line, JAr, to identify a novel drug for the treatment
      of choriocarcinoma. An MTT assay was performed to determine the effects of DMY at
      different concentrations and for different exposure durations. Flow cytometry and
      TUNEL assays were performed to detect apoptosis, and western blotting was
      utilized to investigate the underlying mechanism. The results revealed that DMY
      significantly inhibited JAr cell viability in a time- and dose-dependent manner.
      The flow cytometry and TUNEL assays demonstrated that DMY inhibited proliferation
      by inducing apoptosis. Further analysis by western blotting indicated that the
      protein expression level of BCL-2 associated X, associated protein increased,
      while the protein expression levels of BCL-2 and pro-caspase-3 decreased. These
      findings suggest that DMY induced apoptosis in human choriocarcinoma JAr cells,
      through a mitochondrially mediated apoptotic pathway.

PMID- 30214559
TI  - Clinicopathological and genetic characteristics associated with brain metastases
      from lung adenocarcinoma and utility as prognostic factors.
AB  - Brain metastases (BM) are common in patients with lung adenocarcinoma, and
      represent a significant cause of morbidity in the disease. A more comprehensive
      understanding of the clinicopathological characteristics that serve as prognostic
      factors for survival in patients with BM from lung adenocarcinoma may aid in
      informing treatment strategies for this patient population. In the present study,
      clinicopathological factors, including EGFR mutation status, were evaluated in 59
      patients who were diagnosed with BM from lung adenocarcinoma, and underwent BM
      resection between January 1985 and December 2014 at Fukuoka University Hospital.
      The most frequent subtype of BM from lung adenocarcinoma was solid adenocarcinoma
      (57.6%), followed by papillary adenocarcinoma (22.0%) and acinar adenocarcinoma
      (18.6%). A total of 14 patients (23.7%) exhibited EGFR mutations, which were
      significantly associated with female sex (9/14, 64.3%), non-smoker status (8/14,
      57.1%), BM in the frontal lobes (9/14, 64.3%) and papillary adenocarcinoma (5/14,
      35.7%). Statistical analysis revealed a significant association between non
      smoker status and BM in the frontal lobes, and more favorable disease prognosis.
      The results of the present study suggest that histological and genetic analysis
      of tissue from BM provides information useful for managing treatment of patients
      with resectable BM arising from lung adenocarcinoma.

PMID- 30214560
TI  - Eps15 homology domain 1 promotes the evolution of papillary thyroid cancer by
      regulating endocytotic recycling of epidermal growth factor receptor.
AB  - Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy, and
      it is often observed to overexpress epidermal growth factor receptor (EGFR).
      Previous research has indicated that EH domain-containing 1 (EHD1) is associated
      with EGFR-mediated endocytotic recycling in multiple tumor types. The objective
      of the present study was to determine the protein expression levels and clinical
      significance of EHD1, EGFR, caveolin-1 (CAV-1) and RAB11 family interacting
      protein 3 (RAB11FIP3) in PTC. PTC specimens were analyzed for EHD1, EGFR, CAV-1
      and RAB11FIP3 expression via immunohistochemistry and western blotting. The
      associations between protein expression and clinicopathological features were
      assessed. EHD1, EGFR, CAV-1 and RAB11FIP3 expression levels were increased in
      human PTC. Additionally, the expression level of EHD1 protein was significantly
      associated with tumor size, lymph node metastasis and EGFR expression (P<0.05).
      CAV-1 was associated with tumor size and EGFR expression (P<0.05). EGFR was only
      associated with lymph node metastasis (P=0.027) and RAB11FIP3 was not associated
      with any clinicopathological characteristics. The correlations between EHD1 and
      EGFR (r=0.564, P<0.05), CAV-1 (r=0.865, P<0.01) and RAB11FIP3 (r=0.504, P<0.05)
      were statistically significant. Overall, EHD1, CAV-1 and RAB11FIP3, which are key
      proteins in endocytotic recycling, promote PTC tumorigenesis through the
      regulation of the transport of EGFR.

PMID- 30214561
TI  - Effects of RSF-1 on proliferation and apoptosis of breast cancer cells.
AB  - Effect of interference with chromatin remodeling and spacing factor-1 (RSF-1) on
      proliferation and apoptosis of breast cancer cells was investigated. MCF-7 and
      SKBR-3 cells were cultured in vitro and were divided into 3 groups: control
      group, negative siRNA control group (NC) and RSF-1 siRNA group. Western blot
      analysis was used to detect the expression of RSF protein after interference.
      Cell Counting Kit-8 (CCK-8) method was used to detect the effect of RSF-1 siRNA
      on cell proliferation. Plate cloning assay was used to detect the effect of RSF-1
      siRNA on cell clone formation ability. Annexin V/PI double staining method was
      used to detect the effect of RSF-1 siRNA on cell apoptosis. Effect of RSF-1 siRNA
      on nuclear factor-kappaB (NF-kappaB) and its downstream signaling pathway were
      detected by western blot analysis. Western blot analysis showed that RSF-1 siRNA
      significantly downregulated the expression of RSF-1 protein in MCF-7 and SKBR-3
      cells at 72 h after transfection (P<0.01). Cell proliferation assay showed that
      RSF-1 siRNA significantly reduced the proliferation ability and clone formation
      ability of MCF-7 and SKBR-3 cells compared with the control group (P<0.01).
      Annexin V/PI double staining assay results showed that compared with the control
      group, RSF-1 siRNA significantly increased the apoptosis rate of MCF-7 and SKBR-3
      cells (P<0.01). Helenalin and Rsf-1 siRNA significantly reduced the expression
      levels of p-p65, Bcl-2, and XIAP proteins (P<0.01). Interfering with the
      expression of RSF-1, gene can effectively inhibit the proliferation of MCF-7 and
      SKBR-3 cells and promote their apoptosis. RSF-1 can be used as a potential new
      therapeutic target for the treatment of breast cancer.

PMID- 30214562
TI  - Intensity-modulated radiation therapy combined with concomitant temozolomide for
      brain metastases from lung adenocarcinoma.
AB  - Short-term efficacy, adverse effects and the impact on quality of life (QoL) of a
      concomitant treatment with intensity-modulated radiation therapy (IMRT) and
      temozolomide (TMZ) in patients with brain metastases (BMs) from lung
      adenocarcinoma were evaluated. This study sought to confirm the benefit of adding
      TMZ to IMRT in patients with BMs from lung adenocarcinoma. Nine patients were
      enrolled and received a dose of 30 Gy in 10 daily fractions to clinical tumor
      volume (CTV) according to IMRT, then additional dose of 9 Gy in 3 fractions of
      IMRT was delivered to gross tumor volume (GTV) only with concomitant TMZ (75
      mg/m2/day) orally during RT for 3 weeks. One patient achieved complete response
      (CR) (11.1%), 6 patients obtained partial response (PR) (66.7%), and there were
      no patients in progression. Therefore, objective response (OR) reached 77.8%. The
      main adverse effects included neutropenia, anemia, vomiting, fatigue and
      dizziness. Grade >=3 of hematologic toxicities did not occur. However, the other
      9 patients who received only intensity-modulated radiation had much worse
      results. The CR was 0, PR rate was 44.4%, OR rate was 44.4%. The results
      indicated that the benefit of adding TMZ to IMRT was confirmed in patients with
      BMs from lung adenocarcinoma. The treatment was active, a significant OR was
      observed, and achieved an improvement in QoL demonstrated by QoL grade (p<0.05).

PMID- 30214563
TI  - Study on the expression of p53 and MMP-2 in patients with lung cancer after
      interventional therapy.
AB  - The aim of the study was to investigate the expression of tumor suppressor gene
      p53 and MMP-9 in non-small cell lung cancer (NSCLC) before and after
      chemotherapy, and investigate its association with the effect of chemotherapy and
      prognosis. Fifty-eight elderly NSCLC patients comprised the observation group.
      Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used
      to detect the expression of p53 and MMP-9 in lung cancer tissues before and after
      chemotherapy. Immunohistochemistry and western blot analysis were used to detect
      the expression of p53 and MMP-9 proteins in NSCLC tissue before and after
      chemotherapy. Terminal deoxynucleotidyl transferase nick end-labeling (TUNEL) was
      used to detect apoptotic cells. The association between the effect of
      chemotherapy and the expression of p53 and MMP-9 in lung cancer tissues was
      analysed. RT-qPCR results showed that the expression of p53 and MMP-2 mRNA in the
      tumor tissue after chemotherapy was significantly lower than that in the tumor
      tissue before chemotherapy. Western blot analysis revealed that the expression of
      p53 and MMP-2 protein in the tumor tissue after chemotherapy was significantly
      decreased. The positive expression of p53 and MMP-2 in lung cancer tissues before
      chemotherapy was 76.25 and 71.25%, respectively, and were reduced to 27.50 and
      23.75%, respectively, after chemotherapy. After chemotherapy, the positive rates
      of p53 and MMP-2 were significantly lower than those before chemotherapy. TUNEL
      results showed that the apoptosis index increased significantly after
      chemotherapy. Efficiency of chemotherapy in patients with a negative expression
      of p53 and MMP-2 in lung cancer before chemotherapy was significantly higher than
      that in patients with a positive p53 and MMP-2 expression. A significant
      difference was found in the expression levels of p53 and MMP-2 in lung cancer
      before and after chemotherapy. The findings of the present study indicate that
      the expression levels of p53 and MMP-2 can be used as a predictor of chemotherapy
      sensitivity.

PMID- 30214564
TI  - Correlation between CT features and liver function and p53 expression in
      hepatitis, cirrhosis and hepatocellular carcinoma.
AB  - This study aimed to investigate the correlation between CT features and liver
      function and p53 expression in hepatitis, cirrhosis and hepatocellular carcinoma
      (HCC). Forty patients with HCC, 30 patients with cirrhosis and 30 patients with
      chronic hepatitis were enrolled between December, 2015 and December, 2016. At the
      same time, normal liver tissues collected from 30 patients with hepatic
      hemangioma were used as the normal control group. All the patients were scanned
      by CT. Average body surface area, left outer lobe and caudate lobe volume, and
      the proportions of left outer lobe and caudate lobe to the whole liver were
      calculated. Biochemical indexes of liver function were determined. The
      pathological tissues of all the subjects were analyzed. Compared with the control
      group, total liver volume of the HCC group was significantly reduced (P<0.05).
      Compared with the HCC group, the volume of the left outer lobe increased in the
      hepatitis group and the cirrhosis group. Compared with control group, caudate
      lobe volume increased significantly in the hepatitis group (P<0.05). Compared
      with the control group, the volume of the left outer lobe and the proportion of
      caudate lobe to the whole liver volume was significantly increased in all three
      groups (P<0.05). Liver function-related indicators in the HCC and cirrhosis
      groups were significantly different from those in the control group (P<0.05). The
      expression level of p53 in HCC was significantly higher than that in the control
      group (P<0.05). The accuracy of diagnosis by using both p53 and CT was higher
      than the use of p53 or CT alone. CT can accurately measure the volume of each
      lobe of the liver, and p53 has important clinical values in the diagnosis of
      liver diseases. Thus, the reasonable combination of the two can effectively
      improve the diagnostic accuracy.

PMID- 30214565
TI  - Changes in blood glucose of elderly patients with gastric cancer combined with
      type 2 diabetes mellitus after radical operation and the effect of mediation
      adjustment for blood glucose on the recovery of gastric cancer.
AB  - This study aimed to investigate the changes in blood glucose of elderly patients
      with gastric cancer combined with type 2 diabetes mellitus (T2DM) after radical
      operation. Forty-six patients in DM group and 30 patients in non-DM group
      underwent radical surgery between January, 2007 and January, 2017 in The First
      Hospital of Lanzhou University, and the clinical data were retrospectively
      analyzed. Statistical analysis was conducted to explore the effect of radical
      operation on blood glucose control of the two groups of patients. In 46 patients
      with gastric cancer combined with T2DM, 24 patients received postoperative
      insulin intervention, and the remaining 22 patients did not receive insulin
      intervention. This latter set of patients comprised the non-insulin treatment
      group. Blood glucose control conditions, inflammatory markers, tumor markers and
      their effects on the prognosis were compared between the two groups. Level of
      postoperative blood glucose of the DM group was significantly higher than that of
      the non-DM group (P<0.05), while the level of blood glucose in the insulin
      treatment group was significantly lower than that in the control group (P<0.05).
      Levels of related tumor markers and inflammatory factors of insulin treatment
      group were significantly higher than those of the control group (P<0.05). The 5
      year survival rate of insulin treatment group was significantly higher than that
      of the control group (P<0.05). Our results showed that the level of blood glucose
      was significantly increased in elderly patients with gastric cancer combined with
      T2DM after radical operation, and levels of blood glucose, tumor markers and
      inflammatory factors in elderly gastric cancer patients with T2DM without insulin
      were significantly increased after radical operation, and long-term prognosis is
      poor.

PMID- 30214566
TI  - A tetracycline-inducible CRISPR/Cas9 system, targeting two long non-coding RNAs,
      suppresses the malignant behavior of bladder cancer cells.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) associated
      protein 9 (Cas9) technology has been applied in varied biological studies,
      including cancer studies. However, stable mRNA expression of Cas9 has potential
      risks in future gene therapy. Therefore, in the present study, a tetracycline
      inducible switch was used to control the mRNA expression of Cas9. Long non-coding
      RNAs (lncRNAs) may be important functional regulators in tumor development,
      including in bladder cancer. RNA was designed to simultaneously target two
      lncRNAs, PVT1 and ANRIL, which are considered to be bladder cancer oncogenes. The
      mRNA expression of Cas9 was controlled by doxycycline. Reverse transcription
      quantitative polymerase chain reaction revealed that the expression of PVT1 and
      ANRIL was significantly inhibited by the tetracycline-inducible CRISPR/Cas9
      system. Functional assays demonstrated that this system could inhibit
      proliferation, induce apoptosis and suppress cell migration. Therefore, the
      tetracycline-inducible CRISPR/Cas9 system was demonstrated to repress the
      malignant behavior of bladder cancer cells by controlling the expression of Cas9
      and simultaneously targeting two oncogenic lncRNAs.

PMID- 30214567
TI  - miR-23b suppresses lung carcinoma cell proliferation through CCNG1.
AB  - Lung carcinoma with high incidence rate could be divided into four subtypes,
      including small cell carcinoma, squamous cell carcinoma, adenocarcinoma and large
      cell carcinoma. miR-23b has been reported to have a low expression and play major
      roles in abundant tumors, however there is little research in lung carcinoma and
      hence the purpose of this study was to explore the impact of miR-23b in lung
      carcinoma. The RNA level of miR-23b and cyclin G1 (CCNG1) was measured by reverse
      transcription quantitative PCR. Luciferase activity reporter assay was used to
      verify that CCNG1 is a target of miR-23b. MTT and Transwell assays were utilized
      to test the functional studies of miR-23b in lung cancer cells. In lung carcinoma
      and lung cancer cells miR-23b expression is low compared with that in
      paracancerous tissues and normal lung cells. Low miR-23b expression inhibited
      lung cancer cell proliferation measured by MTT assay. We applied luciferase
      reporter to determine whether CCNG1 is a target of miR-23b and there was a
      negative correlation between them. Moreover, interference with CCNG1 reduced the
      cell proliferation ability, which partially reversed function of miR-23b. miR-23b
      inhibited cell proliferation of lung cancer by directly targeting CCNG1. It is
      suggested that miR-23b/CCNG1 axis may present a new target for the treatment of
      lung cancer.

PMID- 30214568
TI  - Expression of IL-23R and IL-17 and the pathology and prognosis of urinary bladder
      carcinoma.
AB  - Expression of interleukin-23 receptor (IL-23R) and IL-17 in urinary bladder
      carcinoma (UBC) was investigated to explore the correlations with prognosis. IL
      23/IL-17 axis significantly inhibited the development of inflammatory bowel
      disease. Thirty patients with UBC were enrolled in Zhengzhou Central Hospital
      Affiliated to Zhengzhou University from September 2013 to September 2014. Tumor
      tissue and adjacent healthy tissue were collected, and the levels of IL-23R and
      IL-17 mRNA were detected by RT-PCR. Thirty healthy people were also selected to
      serve as normal control group. Serum levels of IL-23R and IL-17 in serum of UBC
      patients and normal controls were detected by ELISA, and the correlations with
      clinical features of UBC were analyzed. Pearson's correlation analysis was used
      to analyze the correlation between IL-23R and IL-17 protein expression. Follow-up
      study was performed by phone or during patient's visit to out-patient department.
      Overall survival (OS) and disease-free survival (DFS) curves were plotted by
      Kaplan-Meier method to analyze the correlation between expression of IL-23R and
      IL-17 and survival time. ROC curve was used to detect the diagnostic values of IL
      23R and IL-17 protein for UBC. Levels of IL-23R and IL-17 mRNA in UBC tissue were
      3.26 and 2.65 times higher than those in adjacent tissue (P<0.05), and serum
      levels of IL-23R and IL-17 protein in UBC patients were significantly higher than
      those in normal control group. Protein expression levels of IL-23R and IL-17 were
      correlated with clinical stage and lymph node metastasis in UBC patients
      (P<0.05), and Cox hazard model showed that L-23R and IL-17 expression may be
      independent factors for UBC (P<0.05), and high expression levels of IL-23R and IL
      17 significantly shortened the OS and DFS (P<0.05). Serum levels of IL-23R and IL
      17 can be used to effectively diagnose clinical stage and lymph node metastasis
      of UBC patients, and the combined diagnosis has a higher sensitivity and
      specificity than the diagnosis using a single factor. These findings indicated
      that expression levels of IL-23R and IL-17 were increased in tumor tissue and
      serum of UBC patients, and the increased expression levels of IL-23R and IL-17
      were correlated with poor prognosis. Detection of IL-23R and IL-17 levels has
      certain clinical significance in the diagnosis and prognosis of UBC.

PMID- 30214569
TI  - Expression levels of miR-205 and miR-506 in colon cancer tissues and their
      relationships with clinicopathological features.
AB  - The study intended to investigate the expression levels of micro ribonucleic acid
      (miR)-205 and miR-506 in colon cancer tissues and their relationships with
      clinicopathological features. The expression levels of miR-205 and miR-506 in
      colon cancer tissues and para-carcinoma normal colonic mucosa tissues were
      detected via fluorescence reverse transcription quantitative polymerase chain
      reaction (RT-qPCR), and the expression levels of the two miRNAs in plasma of
      colon cancer patients and healthy control population were also detected.
      Moreover, the relationships of the two miRNAs with clinicopathological features
      of patients with colon cancer were analyzed. The expression levels of the two
      miRNAs in colon cancer tissues were higher than those in para-carcinoma normal
      colonic mucosa tissues, and also significantly higher in plasma of the colon
      cancer patients than those in the healthy control population. The differences
      were statistically significant (P<0.05). The expression level of miR-205 was
      associated with tumor-node-metastasis (TNM) staging and lymph node metastasis,
      while the expression level of miR-506 was associated with lymph node metastasis.
      The differences were statistically significant (P<0.05). The expression levels of
      miR-205 in the colon cancer tissues and plasma in patients had no significant
      correlation (r=0.467, P=0.081). There was a positive correlation between the
      expression levels of miR-506 in the colon cancer tissues and plasma in patients
      (r=0.599, P=0.038). The expression levels of miR-205 and miR-506 are upregulated
      in the colon cancer patients, both of which may be closely related to the
      occurrence and development of colon cancer, and may become potential tumor
      markers as well as relevant therapeutic targets.

PMID- 30214570
TI  - The expression level of CSDAP1 in lung cancer and its clinical significance.
AB  - Expression level of messenger RNA (mRNA) of cold shock domain protein A
      intronless pseudogene (CSDAP1) in lung cancer tissues was studied. Fresh
      pathological specimens collected from 317 patients with primary lung cancer
      through surgical resection from January 2007 to January 2012 were selected.
      Reverse transcription-polymerase chain reaction (RT-PCR) and western blot
      analysis were used to detect the transcription and translation of CSDAP1 in lung
      cancer tissues and cancer-adjacent normal tissues, and the results were analyzed
      in combination with clinicopathological features and prognosis of lung cancer.
      Among 317 lung cancer specimens, 105 cases (33.1%) had high expression of CSDAP1.
      Among 138 cases of pulmonary adenocarcinoma, 59 cases had high expression of
      CSDAP1, and the high expression rate was 42.8%. Among 170 cases of lung squamous
      cell carcinoma, 46 cases had high expression of CSDAP1, and the high expression
      rate was 27.5% (P<0.05). Three cases of large cell carcinoma and 9 cases of small
      cell carcinoma had extremely low expression or had no expression of CSDAP1. Among
      the 127 lung cancer patients with regional lymph node metastasis, 53 cases
      (41.7%) had high expression of CSDAP1, while among the 190 lung cancer patients
      without regional lymph node metastasis, 52 cases (27.4%) had high expression of
      CSDAP1 (P<0.05). The results also revealed that the expression of CSDAP1 was also
      related to tumor-node-metastasis (TNM) staging of lung cancer. One-year, three
      year and five-year survival rates of lung cancer patients who had no expression
      of CSDAP1 were relatively high (P<0.05). The results suggested that CSDAP1 may
      play an important role in the occurrence, development and judgement of prognosis
      of lung cancer.

PMID- 30214571
TI  - Study of miR-143 expression in stomach cancer.
AB  - The present study was planned to investigate miR-143 expression during stomach
      cancer. The study explored the relationship between miR-143 expression and
      clinicopathological characteristics including proliferation, migration and
      apoptosis of stomach cancer cells. Sixty-three samples from each of stomach
      cancer tissue and surrounding tissue were obtained. Total RNA was extracted. The
      expression levels of miR-143 from stomach cancer tissue as well as from
      surrounding tissue were measured by semi-quantitative PCR. The effects of miR-143
      overexpression on the migration of stomach cancer cells were examined by
      Transwell assay. The effects of miR-143 overexpression on the apoptosis of
      stomach cancer cells were examined by flow cytometer. The expression level of miR
      143 was significantly decreased in stomach cancer tissues in comparison to
      surrounding tissues (P<0.01). Moreover, the expression of miR-143 related well
      with the tumor size, TNM stage, lymphatic metastasis and relapse (P<0.01). On the
      other hand, stomach cancer cell line with overexpression of miR-143, showed
      significant decline in proliferation rate and migration rate comparison to
      control cells (P<0.01). However, it showed significant higher in apoptosis rate
      (P<0.01). The present study concluded that expression of miR-143 is low during
      stomach cancer. Further, higher expression levels of miR-143 have the ability to
      decline proliferation and migration of stomach cancer cells. In this manner, the
      expression level of miR-143 could be used as an important factor to determine the
      severity of stomach cancer.

PMID- 30214572
TI  - Novel ELISA for serodiagnosis of nasopharyngeal carcinoma based on a B cell
      epitope of Epstein-Barr virus latent membrane protein 2.
AB  - Epstein-Barr virus (EBV) is widespread and is associated with nasopharyngeal
      carcinoma (NPC). Serological detection of EBV is commonly used for screening,
      diagnosis and epidemiological surveys of NPC. In the present study, a novel B
      cell multi-epitope peptide fusion protein (EBV-LMP2-3B), which is composed of
      three B cell linear epitopes (RIEDPPFNSLL, TLNLT and KSLSSTEFIPN) of EBV latent
      membrane protein 2 (LMP2), was expressed in a prokaryotic expression system and
      purified using Ni2+-nitrilotriacetate-Sepharose. The immunogenicity and binding
      specificity of EBV-LMP2-3B were evaluated on the basis of antibody responses in
      immunized BALB/c mice, western blotting and indirect immunofluorescence assay.
      Evaluation of EBV-LMP2-3B as a serological diagnostic reagent was performed using
      an indirect ELISA in 198 patients with NPC and 102 healthy adults. These results
      revealed that EBV-LMP2-3B was able to eliminate the high-titer serum antibody
      response in BALB/c mice. Western blot analysis and indirect immunofluorescence
      assay confirmed that the mouse immune sera recognized the native LMP2. Compared
      with healthy adults, patients with NPC demonstrated significantly greater
      reactivity to EBV-LMP2-3B (P<0.05). Furthermore, it was possible to effectively
      detect specific IgG in sera from patients with NPC, with a sensitivity of 91.91%
      and specificity of 93.14%, representing an improvement over the traditional viral
      capsid antigen-IgA-based detection method with 59.59% sensitivity and 75.49%
      specificity. In conclusion, the EBV-LMP2-3B protein may be used as a serological
      diagnostic reagent to screen for and diagnose NPC.

PMID- 30214573
TI  - Abnormal changes in the quantity and function of osteoblasts cultured in vitro in
      patients with myelodysplastic syndrome.
AB  - Changes in bone marrow niches can lead to the occurrence of myelodysplastic
      syndrome (MDS). As an important part of the bone marrow niche, osteoblasts serve
      a key role in the progression of MDS. The present study investigated the quantity
      and function of osteoblasts and, through in vitro assays, detected changes in
      signaling pathways and the association with progression in MDS patients. The
      ratios of osteoprogenitors (CD34+OCN+) and OCN+CD34-Lin- osteoblasts in MDS
      patients were significantly less than those of normal controls. The results of
      this study demonstrated that the quantity and activity of osteoblasts in MDS
      patients were lower than those in normal controls. Furthermore the activity of
      osteoblasts in patients correlated with the severity of MDS. The quantity of
      osteoblasts cultured in vitro from high-risk and very high-risk MDS patients (WHO
      Classification-Based Prognostic Scoring System score 3-6) was decreased. The
      levels of T-cell immunoglobulin and mucin domain-containing 3 (TIM3) and Jagged 1
      were also increased in the osteoblasts in vitro. These results indicated that
      osteoblasts are abnormally altered in MDS patients, and that there are
      associations between abnormal changes of osteoblasts and the severity of MDS.

PMID- 30214574
TI  - Ectopic expression of E3 ubiquitin-protein ligase 2 in glioma and enhances
      resistance to apoptosis through activating nuclear factor kappa-light-chain
      enhancer of B cells.
AB  - Nuclear factor kappa-light-chain-enhancer of B cells (NF-kappaB) is one of the
      most important tumorigenic factors. Although it has been established that NF
      kappaB is overly activated in human glioma cells, the molecular mechanisms that
      lead to the signal transduction to NF-kappaB and thereby the induction of
      resistance to apoptosis remain poorly understood. The present study demonstrated
      that mRNA and protein levels of E3 ubiquitin-protein ligase 2 (MIB2) were
      markedly upregulated in glioma cell lines and clinical samples.
      Immunohistochemical analysis also revealed high levels of MIB2 expression in
      glioma specimens. Ectopic overexpression of MIB2 was established in glioma cell
      lines to investigate its fundamental roles in the response of human glioma to
      apoptotic inducers. The results indicated that ultraviolet irradiation-induced
      cell apoptosis was inhibited with MIB2 overexpression in glioma cells. Notably,
      knockdown of MIB2 using RNA interference was able to increase the sensitivity of
      glioma cells to the pro-apoptotic agents. The present study identified that MIB2
      induces NF-kappaB activation and facilitates the resistance of glioma cell to
      apoptosis. It was proposed that MIB2 may not only be an important hallmark to
      glioma disease progression, but that it may also offer novel clinical strategies
      to overcome resistance to cancer therapies.

PMID- 30214575
TI  - Novel strategy of sirolimus plus thymalfasin and huaier granule on tumor
      recurrence of hepatocellular carcinoma beyond the UCSF criteria following liver
      transplantation: A single center experience.
AB  - Although liver transplantation (LT) lengthens the survival time of patients with
      hepatocellular carcinoma (HCC), LT patients exhibit a high recurrence rate;
      particularly those that had advanced HCC associated with the tumor biological
      characteristics and long-term application of immunosuppressants. A consensus on
      optimal prophylaxis and treatment for recurrent HCC following LT does not
      currently exist. The present study retrospectively analyzed data from 36 non
      University of California at San Francisco criteria-eligible patients with
      advanced HCC who underwent LT, and then treated them with sirolimus (SRL)-based
      therapy with thymalfasin and huaier granules (SRL+, n=18), or with tacrolimus
      based therapy (controls; n=18). The SRL+ group had significantly longer
      recurrence times (P=0.008) and survival times (P<0.0001) (OS, 1-year: 100%, 3
      year: 94.4%, 5-year: 77.8%; DFS, 1-year: 88.9%, 3-year: 55.6%, 5-year: 50.0%).
      Furthermore, compared with pre-LT values and the control group, the SRL+ group
      had significantly lower serum alpha-fetoprotein (AFP) levels (both P<0.0001) and
      percentage of Forkhead box P3 (FoxP3)+ Treg lymphocytes (P<0.001) during the
      first year. In the SRL+ group, FoxP3+/cluster of differentiation (CD)8+ Treg
      lymphocyte percentages decreased significantly following LT (P<0.001); however,
      CD8+/CD3+ T-cells significantly increased (P<0.001). Levels of serum AFP and
      FoxP3+ Treg cells increased when tumors relapsed, and decreased to near-normal
      when relapse foci were cured or stabilized. SRL+ therapy may decrease AFP and
      Treg levels, while increasing CD8+ T cells, indicating an associated mechanism
      among them. In conclusion, SRL+ therapy appears to be safe and effective in
      preventing HCC recurrence following LT with no significant adverse events, and
      warrants further investigation.

PMID- 30214576
TI  - Hepatitis B virus-X protein regulates high mobility group box 1 to promote the
      formation of hepatocellular carcinoma.
AB  - Hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma
      (HCC). HBV X protein (HBx) is an important carcinogen for HBV-induced HCC. When
      the HBx gene is integrated into the host cell genome, it is difficult to
      eradicate. The identification of an effective target to inhibit the oncogenic
      function of HBx is therefore critically important. The present study demonstrated
      that HBx, particularly truncated HBx, was expressed in several HBV-derived cell
      lines (e.g., Hep3B and SNU423). By analyzing data from The Cancer Genome Atlas,
      it was revealed that high expression of high mobility group box 1 (HMGB1) was
      associated with the process and prognosis of HCC. In vitro experiments confirmed
      that HBx could regulate the expression of HMGB1 and knockdown of HMGB1 could
      decrease the ability of HBx to promote cellular proliferation. HBx could also
      upregulate six transcription factors (GATA binding protein 3, Erb-B2 receptor
      tyrosine kinase 3, heat shock transcription factor 1, nuclear factor kappaB
      subunit 1, TATA-box binding protein and Kruppel-like factor 4), which could
      directly regulate HMGB1. By analyzing genes that are co-expressed with HMGB1,
      several signaling pathways associated with the development of HCC were
      identified. HBx and HMGB1 were revealed to be involved in these pathways, which
      may be the mechanism by which HBx promotes HCC by regulating HMGB1. These
      findings suggested that HMGB1 may be an effective target for inhibiting HBV
      induced HCC.

PMID- 30214577
TI  - Prognostic validation of the updated 8th edition Tumor-Node-Metastasis
      classification by the Union for International Cancer Control: Survival analyses
      of 307 patients with surgically treated gallbladder carcinoma.
AB  - In December 2016, the Union for International Cancer Control (UICC) published the
      8th edition of the Tumor-Node-Metastasis (TNM) classification of malignant
      tumors, including a number of vital changes in the definitions of the T2
      category, the N category and the stages of gallbladder cancer (GBC). The clinical
      value of this newly updated classification in patients with surgically treated
      GBC has not been rigorously validated. The present study aimed to analyze the
      prognosis of patients with GBC in a high-volume surgical unit, and to validate
      the prognostic value of the new UICC TNM classification, particularly the main
      changes in the stages of GBC. Data from 307 patients who were surgically treated
      and histopathologically diagnosed with GBC between January 2011 and July 2016 in
      The West China Hospital (Chengdu, Sichuan, China) were retrospectively collected
      and analyzed. The new UICC criteria distributed 32, 60, 99 and 116 eligible
      patients in stages I, II, III and IV, respectively. The differences in overall
      survival time between each stage (I-IV) demonstrated statistical significance
      (P<0.05). As a result of the main change of this classification, the novel
      definitions of T2a and T2b effectively stratified the prognosis of patients with
      T2 GBC (P<0.001). Furthermore, patients with stage IIa tumors also obtained
      significantly improved overall survival time compared with patients with stage
      IIb tumors (P=0.04), whereas the comparison between patients with stage IIb and
      IIIa tumors did not present any notable difference (P=0.20). Additionally, the
      new N category stratified the survival of the patients effectively (P<0.001).
      Together with curative resection, this latest classification was indicated to be
      an independent predictor of survival via multivariate analysis (hazard ratio,
      6.25; 95% confidence interval, 3.81-10.26; P<0.001). In conclusion, the newly
      updated UICC TNM classification could effectively reflect the clinical outcome of
      patients with surgically treated GBC. Furthermore, tumor location could predict
      the survival of surgically treated T2 GBC. The novel classification of the N
      category by the number of lymph nodes involved was also demonstrated to be valid.

PMID- 30214578
TI  - Butyrate upregulates the TLR4 expression and the phosphorylation of MAPKs and NK
      kappaB in colon cancer cell in vitro.
AB  - Microbiota and its induced inflammation in colorectal mucosa have been considered
      risk factors for the development of colorectal carcinogenesis. Previous studies
      demonstrated that the coexisting elements of microbiota in the gut, such as short
      chain fatty acids (SCFAs) and lipopolysaccharides (LPS), which exhibited
      regulatory effects on the intestinal epithelial cells individually.
      Unfortunately, the association between butyrate and the toll-like receptor (TLR)
      signaling pathway in the development of colon cancer is not fully elucidated. In
      the present study, by culturing human colon cancer SW480 cells or mouse colon
      cancer CT26 cells with butyrate and/or TLR4 ligand LPS in vitro, it was
      identified that butyrate suppressed the growth and promoted apoptosis of these
      cancer cells. Notably, the expression levels of TLR4 and CD14 were markedly
      increased on these butyrate-treated cells, but not on LPS-alone treated cells.
      Additionally, butyrate treatment induced the phosphorylation of extracellular
      signal-regulated kinase, tumor protein 38, c-Jun NH2-terminal kinase and nuclear
      factor-kappaB (NF-kappaB) p65, and then promoted the pro-inflammatory cytokine
      tumor necrosis factor-alpha, but not interleukin 6 secretion in SW480 and CT26
      cells. Therefore, butyrate treatment regulates the expression of TLR4, mitogen
      activated protein kinase and NF-kappaB signal pathway activation and pro
      inflammatory response in vitro. Although the exact mechanisms have not been fully
      explored, these results suggested that butyrate and LPS-TLR4 signaling mediated
      innate immunity in colon cancer cells through two distinct but inter-regulated
      pathways. Thus, butyrate can further initiate innate immunity against tumor cells
      by upregulating the TLR4 expression and activation to preserve intestinal
      homeostasis.

PMID- 30214579
TI  - High expression of programmed cell death protein 1 on peripheral blood T-cell
      subsets is associated with poor prognosis in metastatic gastric cancer.
AB  - Immune checkpoints in solid tumors serve important roles in metastasis. The
      present study was designed to explore the expression of programmed cell death
      protein 1 (PD-1) on peripheral blood T-cell subsets and its role in the
      clinicopathological features and prognosis of patients with metastatic gastric
      cancer. The expression of PD-1 in peripheral blood T-cell subsets was detected in
      100 metastatic gastric cancer patients prior to the first line chemotherapy by
      flow cytometric analysis. The potential associaton between the peripheral blood T
      cell subsets PD-1 level and the clinicopathological features of patients with
      metastatic gastric cancer and the clinical outcomes was analyzed. The percent of
      high PD-1 expressed cluster of differentiation (CD)3+, CD3+CD4+ and CD3+CD8+ T
      cells was 20.4, 13.0 and 9.4%, respectively in patients with metastatic gastric
      cancer. The overall survival (OS) and progression-free survival (PFS) rate of the
      100 patients with metastatic gastric cancer was 12.2 and 3.9 months,
      respectively. Kaplan-Meier curve with long-rank analysis indicated that patients
      with higher PD-1+/CD3+, PD-1+/CD3+CD4+ and PD-1+/CD3+CD8+ levels had a worse
      prognosis (all P<0.05). Univariate and multivariate analysis revealed that high
      PD-1+/CD3+ [hazard ratio (HR), 2.145; P=0.015], high PD-1+/CD3+CD4+ (HR, 1.866;
      P=0.034) and high PD-1+/CD3+CD8+ (HR, 1.817; P=0.033) level in peripheral blood
      were independent risk factors for predicting the survival time of patients with
      metastatic gastric cancer. High PD-1+/CD3+, high PD-1+/CD3+CD4+ and high PD
      1+/CD3+CD8+ expression conferred a lower overall survival rate in patients with
      metastatic gastric cancer. These results suggest that high PD-1 expression on
      peripheral blood T-cell subsets may potentially be novel prognostic biomarker for
      metastatic gastric cancer.

PMID- 30214580
TI  - High serum Ephrin-B2 levels predict poor prognosis for patients with gastric
      cancer.
AB  - Gastric cancer is an intractable disease with a poor prognosis and limited
      treatment options. Its treatment remains a major clinical challenge worldwide.
      Ephrin-B2 is upregulated and involved in tumor growth in various types of cancer.
      However, the association between ephrin-B2 and prognosis of gastric cancer, and
      the potential of ephrin-B2 as a therapeutic target remains unknown. The present
      study investigated ephrin-B2 as a prognostic factor and a therapeutic target for
      gastric cancer. Reverse transcription-quantitative polymerase chain reaction was
      performed to detect the protein expression level of ephrin-B2 in gastric cancer
      serum samples (n=162) and healthy serum samples (n=165). It was revealed that the
      protein expression level of ephrin-B2 was significantly upregulated in gastric
      cancer serum samples compared with the healthy samples. Ephrin-B2 protein
      expression was associated with tumor size (P<0.001), metastasis (P=0.02) and TNM
      stage (P=0.03), and was indicated to be an independent prognostic factor for
      gastric cancer. Furthermore, the Kaplan-Meier survival curve demonstrated that
      patients with high ephrin-B2 protein expression had shorter overall and
      progression-free survival rates than those with low ephrin-B2 protein expression.
      Ephrin-B2 protein expression was induced by small interfering RNA (siRNA)
      transfection of HGC27 and MKN-45 cells, significantly impeding cell viability and
      inducing apoptosis of HGC27 and MKN-45 cells compared with the respective
      negative control (NC) group. Thus, to the best of our knowledge, the present
      study indicates that ephrin-B2 functions as an oncogene in gastric cancer, and
      that serum ephrin-B2 level may be a promising non-invasive prognostic indicator,
      as well as a therapeutic target for gastric cancer.

PMID- 30214582
TI  - Osthole attenuates angiogenesis in an orthotopic mouse model of hepatocellular
      carcinoma via the downregulation of nuclear factor-kappaB and vascular
      endothelial growth factor.
AB  - Osthole has been demonstrated to have antitumor activity. Previous studies by our
      group indicated that osthole effectively inhibited tumor growth in hepatocellular
      carcinoma (HCC) through the induction of apoptosis and enhancement of antitumor
      immune responses in mice. The importance of angiogenesis in the proliferation,
      invasion and metastasis of tumor cells in HCC is well established. The present
      study aimed to investigate the effects of osthole on angiogenesis in an
      orthotopic mouse model of HCC. Orthotopic HCC in mice was established, and
      osthole at 61, 122 and 244 mg/kg was administered intraperitoneally once daily to
      the tumor-bearing mice for 14 consecutive days. Immunohistochemistry was
      performed to analyze the microvessel density (MVD) of tissues, and the level of
      vascular endothelial growth factor (VEGF) was measured by ELISA. The protein
      levels of nuclear factor-kappaB (NF-kappaB) p65 and IkappaB-alpha were also
      detected by western blotting. MVD was positively correlated with tumor weight in
      the orthotopic mouse model of HCC. Osthole administration significantly decreased
      MVD in tumor and adjacent tissues, and inhibited tumor growth. Furthermore,
      osthole downregulated the expression of VEGF and NF-kappaB p65, and upregulated
      IkappaB-alpha expression in tumor and adjacent tissues. To the best of our
      knowledge, the results of the present study demonstrated for the first time that
      osthole inhibits angiogenesis in an orthotopic mouse model of HCC, which may be
      one of the mechanisms underlying the anti-HCC activity of osthole, which in turn
      may be mediated by the NF-kappaB/VEGF signaling pathway. Therefore, osthole, a
      potential angiogenesis inhibitor and immune system enhancer, may be a promising
      lead compound for the treatment of HCC.

PMID- 30214581
TI  - Aberrant promoter methylation of PCDH10 as a potential diagnostic and prognostic
      biomarker for patients with breast cancer.
AB  - Protocadherin-10 (PCDH10) is a tumor suppressor gene. Its expression level is
      downregulated by promoter methylation in certain types of human tumors. The aim
      of the present study was to examine the expression level and promoter methylation
      status of PCDH10 in breast cancer cells and to evaluate the association of PCDH10
      methylation and tumor progression and prognosis. MethyLight was used to detect
      the methylation status of PCDH10 in breast cancer tissues and healthy breast
      tissues. Reverse transcription-quantitative polymerase chain reaction was used to
      assess the mRNA expression level of PCDH10, as well as to evaluate the
      association between PCDH10 methylation and clinicopathological features, along
      with patients' overall survival (OS). PCDH10 5'-C-phosphate-G-3' (CpG) methylated
      sites were identified in tumor tissues and matched healthy tissues (n=392). Tumor
      tissues and matched healthy tissues exhibited identifiable PCR results, with
      PCDH10 gene promoter methylation identified in ductal carcinoma in situ (66%),
      invasive ductal carcinoma (82%), invasive ductal carcinoma with lymph node
      metastasis (85.32%) and hereditary breast cancer tissues (72.37%). PCDH10 mRNA
      expression was significantly decreased in breast cancer tissues compared with
      healthy breast tissues (P=0.032). PCDH10 methylation was associated with tumor
      size (P=0.004), but not associated with other clinical factors. Survival analysis
      revealed that the patients exhibiting methylated-PCDH10 had significantly poorer
      OS times than patients exhibiting unmethylated-PCDH10 (P<0.0001). Receiver
      operating characteristic analysis indicated a sensitivity of 75%, a specificity
      of 62.5%, and an area under the curve of 0.682 for PCDH10. Additionally, the
      results of the present study indicated that PCDH10 methylation status may be a
      useful diagnostic and prognostic evaluation biomarker for breast cancer. The
      results suggested that PCDH10 methylation is a common occurrence in primary
      breast cancer and is associated with poor survival rates among patients with
      breast cancer.

PMID- 30214583
TI  - H19 contributes to poor clinical features in NSCLC patients and leads to enhanced
      invasion in A549 cells through regulating miRNA-203-mediated epithelial
      mesenchymal transition.
AB  - Recent studies have demonstrated that the overexpression of H19 may contribute
      towards development of tumorigenesis in various types of cancer. To investigate
      the role of H19 in the development of non-small cell lung cancer (NSCLC), 76
      NSCLC tissues samples and their adjacent normal tissue samples were collected.
      Expression level of H19, and its association with clinicopathological features
      and overall survival was analyzed. It was found that compared with normal
      adjacent tissues, H19 expression was elevated in NSCLC tissues along with a
      decreased miR-203 expression level. It was also found that patients who were in
      advanced clinical stages had a higher H19 and a lower miR-203 expression compared
      to normal tissues. The overall survival time of patients with higher H19
      expression was shorter compared with the lower H19 expression group. Upregulation
      of A549 enhanced cell proliferation and promoted invasion. Overexpression of H19
      stimulated the epithelial-mesenchymal transition (EMT) process in lung cancer
      cells and demonstrated typical morphological characteristics of EMT. The level of
      mesenchymal marker protein, such as Vimentin and SNAI1 increased; while CDH1
      protein level decreased. Also, H19 negatively regulated miR-203. Inhibition of
      H19 attenuated miR-203 induced EMT process. Upregulation of H19 contributes to
      poor clinical features in patients with NSCLC, induces occurrence of EMT,
      promotes proliferation and stimulates cell invasion in NSCLC cell line through
      regulating miRNA-203 mediated EMT.

PMID- 30214584
TI  - Influence of SLCO1B1 in gastric cancer patients treated with EOF chemotherapy.
AB  - Cytochrome-P450 enzymes, ATP-binding cassette transporters, and solute carriers
      mediate drug metabolism as metabolic enzymes and membrane transporters,
      respectively. The present study investigated whether single nucleotide
      polymorphisms (SNPs) in genes encoding these proteins were predictive or
      prognostic factors in patients with metastatic gastric cancer (MGC) undergoing
      chemotherapy. A retrospective study of 108 MGC patients who received epirubicin,
      oxaliplatin, and 5-fluorouracil (EOF) as first-line treatment was performed. A
      total of 13 SNPs were genotyped, including SLCO1B1 (rs4149056), SLC2A9
      (rs16890979, rs6449213, rs734553), ABCG2 (rs2231142), CYP2C9 (rs1057910,
      rs1799853), CYP2C19 (rs72552267, rs28399504, rs56337013, rs41291556) and CYP1A2
      (rs12720461, rs56107638). The associations between these genotypes and disease
      control rate (DCR), progression-free survival (PFS) and overall survival (OS)
      were analyzed. Patients with SLCO1B1 rs4149056 TT genotype had a significantly
      shorter OS compared with those with a C allele (CC + CT; 312 vs. 565 days,
      P=0.039). Multivariate analysis revealed that the rs4149056 TT homozygous
      genotype was an independent prognostic factor for shorter OS (hazard ratio:
      2.565, 95% confidence interval: 1.215-5.415, P=0.014). However, no significant
      associations between SLCO1B1 rs4149056 and PFS were observed, between the other
      12 SNPs and PFS or OS, or between any of the 13 SNPs and DCR. In conclusion,
      SLCO1B1 rs4149056 TT may be an independent predictor of survival in patients with
      MCG treated with EOF chemotherapy.

PMID- 30214585
TI  - Stereotactic body radiotherapy for centrally-located lung tumors with 56 Gy in
      seven fractions: A retrospective study.
AB  - Stereotactic body radiotherapy (SBRT) for centrally-located lung tumors remains a
      challenge because of the increased risk of treatment-related adverse events
      (AEs), and uncertainty around prescribing the optimal dose. The present study
      reported the results of central tumor SBRT with 56 Gy in 7 fractions (fr) at the
      University of Tokyo Hospital. A total of 35 cases that underwent SBRT with or
      without volumetric-modulated arc therapy consisting of 56 Gy/7 fr for central
      lung lesions between 2010 and 2016 at the University of Tokyo Hospital were
      reveiwed. A central lesion was defined as a tumor within 2 cm of the proximal
      bronchial tree (RTOG 0236 definition) or within 2 cm in all directions of any
      critical mediastinal structure. Local control (LC), overall survival (OS), and
      AEs were investigated. The Kaplan-Meier method was used to estimate LC and OS.
      AEs were scored per the Common Terminology Criteria for Adverse Events Version
      4.0. Thirty-five patients with 36 central lung lesions were included. Fifteen
      lesions were primary non-small cell lung cancer (NSCLC), 13 were recurrences of
      NSCLC, and 8 had oligo-recurrences from other primaries. Median tumor diameter
      was 29 mm. Eighteen patients had had prior surgery. At a median follow-up of 13.1
      months for all patients and 18.3 months in surviving patients, 22 patients had
      died, ten due to primary disease (4 NSCLC), while three were treatment-related.
      The 1- and 2-year OS were 57.3 and 40.4%, respectively, and median OS was 15.7
      months. Local recurrence occurred in only two lesions. 1- and 2-year LC rates
      were both 96%. Nine patients experienced grade >=3 toxicity, representing 26% of
      the cohort. Two of these were grade 5, one pneumonitis and one hemoptysis.
      Considering the background of the subject, tumor control of our central SBRT is
      promising, especially in primary NSCLC. However, the safety of SBRT to central
      lung cancer remains controversial.

PMID- 30214586
TI  - Time series analysis of death of residents with malignant granules in Shenyang,
      China.
AB  - The aim of the study was to find out the association between air pollution and
      meteorological conditions with the death of residents living in Shenyang due to
      malignant tumors. Tumor related death data of residents of five urban districts
      in Shenyang were obtained from Shenyang Center for Disease Control and
      Prevention. Daily temperature, pressure, wind speed and humidity data of Shenyang
      from 2010 to 2015 were obtained from Shenyang Meteorological Bureau. Urban air
      pollution data were obtained from the Shenyang Environmental Monitoring Center
      Station, Shenyang Environmental Protection Bureau of China. All data were
      analyzed by the Poisson regression model. During the period from 2010 to 2015,
      the number of deaths among malignancies in Shenyang was 215,141,000, and the
      death rate of malignancies in Shenyang was increasing year by year from 2010 to
      2015. Mortality rate is higher in men than in women, and mortality rate increased
      with aging and the highest mortality rate was observed in the 75-80 years age
      group. Average concentration of aerodynamic diameter of <10 um particles, the
      aerodynamic diameter of <2.5 um particles, sulfur dioxide (SO2) and nitrogen
      dioxide (NO2) was 122.37, 74.75, 79.36, and 47.65 ug/m3, respectively. After
      control of confounding factors, it was observed that every 10 ug/m3 increase of
      PM2.5 is followed by the 0.024% (95% confidence interval: 0.005% and 0.043%)
      increase of malignant tumor mortality rate. The results show that the increase of
      air pollution is related to the number of malignant tumors-related deaths in
      Shenyang, China, and season, sex and age are also influencing factors.

PMID- 30214587
TI  - Sequential treatment with celecoxib and bortezomib enhances the ER stress
      mediated autophagy-associated cell death of colon cancer cells.
AB  - Treatment with celecoxib and bortezomib as single chemotherapeutic agents reduces
      the viability and proliferation of colorectal cancer cells. The use of these
      agents in combination with other chemotherapeutic agents is usually associated
      with adverse effects. In the present study, a combination of celecoxib and
      bortezomib was investigated for potential synergistic effects in colon cancer
      cells. The sequential exposure to celecoxib with bortezomib synergistically
      induced apoptotic death in human colon cancer cells compared with groups treated
      with a single drug or other drug combinations. c-Jun N-terminal kinase/p38
      mitogen-activated protein kinase-induced endoplasmic reticulum (ER) stress
      through serial exposure to celecoxib and bortezomib may have induced the
      intracellular Ca2+ release, leading to the generation of autophagosomes in p53
      expressing HCT-116 cells. Targeted inhibition of p53 activity or ER stress or
      treatment with the Ca2+-chelating agent BAPTA-AM suppressed the ER stress
      mediated Ca2+ release and apoptosis. Although p53-/- HCT-116 cells were less
      sensitive to sequential treatment with celecoxib and bortezomib, co-localization
      of autophagosomes was detected in the absence of CCAAT-enhancer-binding protein
      homologous protein expression. Treatment of p53-/- HCT-116 cells with BAPTA-AM
      did not inhibit apoptosis following serial treatment with celecoxib and
      bortezomib. These results suggest that the order of drug administration is
      important in treating cancer and that the sequential treatment with celecoxib and
      bortezomib enhances the ER stress-mediated autophagy-associated cell death of
      colon cancer cells, regardless of p53 expression.

PMID- 30214588
TI  - Antitumor effect of the paclitaxel-eluting membrane in a mouse model.
AB  - Local treatment of primary bile duct cancer, which grows locally at the primary
      lesion and seldom metastasizes to distant sites, is challenging. The present
      study evaluated the antitumor effect, systemic toxicity, biodistribution and
      survival benefit of the paclitaxel-eluting polyurethane membrane in a tumor
      model. Membranes containing various amounts of paclitaxel (0, 100, 300, 600 and
      1,200 ug/disc) were inserted beneath the tumor mass in mouse models. Tumor size
      and body weight of the tumor models were monitored for 26 days after insertion of
      the membrane. The terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling assay was performed in the tumor tissues. High-performance liquid
      chromatography was performed for evaluation of paclitaxel concentration in
      peripheral tissues. Tumor volumes on day 26 of membrane treatment were decreased
      in a dose-dependent manner. No significant difference in body weight was observed
      in the groups. A greater number of apoptotic cells were counted per high power
      field in tumor tissues following an increase of paclitaxel concentration. In the
      1,200 ug-group, concentrations of paclitaxel were significantly higher in tumors
      compared with those of other tissues and serum. The paclitaxel-eluting membrane
      demonstrated a significant and dose-dependent antitumor activity, and did not
      exert systemic toxicity in the tumor model.

PMID- 30214589
TI  - miRNA-199a-5p suppresses proliferation and invasion by directly targeting NF
      kappaB1 in human ovarian cancer cells.
AB  - The aberrant expression of microRNA (miRNA)-199a-5p has been frequently reported
      in a number of cancer types, but to the best of our knowledge, this has not been
      reported in ovarian cancer (OC). The role and the molecular mechanism of miR-199a
      5p in OC have not been reported. Therefore, the present study investigated the
      effects of miR-199a-5p overexpression on the proliferation and invasion of OC
      cells. The level of miR-199a-5p in OC cell lines was determined by reverse
      transcription-quantitative polymerase chain reaction. The miR-199a-5p mimic was
      transiently transfected into OC cells using LipofectamineTM 2000 reagent.
      Subsequently, the BrdU-ELISA results indicated that the exogenous expression of
      miR-199a-5p inhibited cell proliferation. In addition, miR-199a-5p overexpression
      was able to inhibit the invasion of HO-8910 and ES-2 cells. RT-qPCR was performed
      to determine the expression of matrix metalloproteinase (MMP)-2 and -9 in OC
      cells. NF-kappaB1 expression was reduced by upregulation of miR-199a-5p.
      Bioinformatics analysis predicted that NF-kappaB1 was a potential target of miR
      199a-5p. Luciferase reporter assay further confirmed that miR-199a-5p was able to
      directly target the 3'UTR of NF-kappaB1. In conclusion, miRNA-199a-5p may
      suppress the proliferation and invasion of human ovarian cancer cells by directly
      targeting NF-kappaB1.

PMID- 30214590
TI  - Downregulation of peroxiredoxin II suppresses the proliferation and metastasis of
      gastric cancer cells.
AB  - Peroxiredoxin (Prx) II is an imperative member of the superfamily of peroxidases.
      It serves an essential role in scavenging organic hydroperoxide and H2O2. It is
      involved in the development of various malignant tumors. In order to investigate
      the significance of Prx II expressions level in gastric cancer (GC),
      downregulation of Prx II was performed to investigate its role in the
      proliferation and migration of gastric adenocarcinoma cells. In GC cells and 45
      GC specimens, the mRNA and protein expression levels of Prx II were determined
      using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and
      western blot analysis, respectively. The Prx II expression profile in another 116
      GC specimens was also detected with immunohistochemistry (IHC). The changes in
      the proliferation and migration of MKN45 and MGC-803 cells folllowing
      transfection with small interfering RNA (siRNA) were detected by cell counting
      kit (CCK)-8, western blot analysis, and Transwell migration and invasion assays.
      The results revealed that the expression of Prx II in GC tissues and GC cells
      were significantly upregulated compared with the normal control. There was a
      significant association between the expression level of Prx II and various
      factors, including tumor size, histological differentiation, the depth of
      invasion, the stage of tumor-node-metastasis (TNM) and lymph node metastasis in
      GC (P<0.05). Survival in patients with higher Prx II expression was significantly
      decreased compared with those with lower Prx II expression (P<0.01). Prx II,
      depth of invasion, lymph node metastasis and distant metastasis were identified
      as independent prognosis factors of GC (P<0.05). Knockdown of Prx II
      significantly suppressed the proliferation and the migration of GC cells. These
      experiments revealed that Prx II promotes the development of GC, affecting the
      survival of patients with GC.

PMID- 30214591
TI  - AZD8055 inhibits ACTH secretion in a case of bilateral ACTH-secreting
      pheochromocytoma.
AB  - Ectopic adrenocorticotropic hormone (ACTH) syndrome is usually caused by
      pulmonary and bronchial tumors and rarely by pheochromocytoma. To date, the
      majority of ACTH-secreting pheochromocytomas have been unilateral, with the
      exception of two cases. A 54-year-old male presented with hypertension and
      bilateral adrenal tumors. The patient did not report having classic cushingoid
      features or experience of paroxysmal headaches or sweating, but presented with a
      slight abdominal obesity. The patient was clinically and pathologically diagnosed
      with bilateral ectopic ACTH-secreting pheochromocytomas. Whole-exome sequencing
      demonstrated that the 19 pheochromocytoma-related genes were unmutated. The
      pheochromocytomas on the two sides exhibited negative ACTH staining, but the ACTH
      concentration was markedly higher in the tumor tissue homogenates than in those
      tumors of another 3 patients with non-ACTH secretion pheochromocytoma. Electron
      microscopy identified two types of neuroendocrine cells in the tumor tissues.
      Primary culture of the pheochromocytoma cells revealed that ACTH secretion was
      inhibited by a mechanistic target of rapamycin inhibitor, AZD8055.

PMID- 30214592
TI  - Prostaglandin E2 triggers cytochrome P450 17alpha hydroxylase overexpression via
      signal transducer and activator of transcription 3 phosphorylation and promotes
      invasion in endometrial cancer.
AB  - Prostaglandin E2 (PGE2) is the most common prostaglandin in the human body,
      meaning that its malfunction impacts on the development of numerous diseases.
      Prostaglandin E synthase 2 (PTGES2) is involved in the synthesis of PGE2. In the
      present study, immunohistochemistry of PTGES2 was performed in 152 patients with
      endometrial cancer and in 66 patients with normal endometria. The results
      indicate a notable association among increased expression of PTGES2 and age
      (P=0.0092) and the depth of myometrial invasion (P<0.0001). Reverse transcription
      quantitative polymerase chain reaction and western blot analysis demonstrated
      that cytochrome P450 17alpha hydroxylase (CYP17), an enzyme for androgen
      synthesis, is overexpressed following PGE2 stimulation via signal transducer and
      activator of transcription 3 (STAT3) phosphorylation. ELISA also detected
      increased androgen (testosterone) secretion. Further invasion of endometrial
      cancer cells was induced at high androgen levels and when CYP17 was
      overexpressed. Furthermore, the present study observed that CYP17 is
      overexpressed via STAT3 phosphorylation in endometrial cancer cells, which grow
      at a high concentration of PGE2, resulting in increased androgen secretion.
      Concentrations of estrogen and progesterone were not elevated, while the
      concentration of androgens was. Overall, a high concentration of androgens caused
      increased invasion of endometrial cancer cells. A high concentration of
      androgens, which is initiated by a high expression of PTGES2 and a high
      concentration of PGE2, is an important promoter of myometrial invasion in
      endometrial cancer.

PMID- 30214593
TI  - Downregulation of high mobility group protein box-1 resensitizes ovarian cancer
      cells to carboplatin.
AB  - Ovarian cancer, one of the most common types of cancer, has the highest mortality
      among all gynecological malignancies. The development of acquired drug resistance
      is the leading cause of chemotherapy failure. To study the mechanism underlying
      drug resistance in ovarian cancer, a drug-resistant ovarian cancer SKOV3 cell
      line was developed using the chemotherapeutic agent carboplatin (SKOV3-Carb) in
      the present study. It has been reported that high-mobility group protein box-1
      (HMGB1) is associated with the chemoresistance of tumor cells. Therefore, the
      probable involvement of HMGB1 in the development of carboplatin resistance in
      ovarian cancer SKOV3 cells was investigated. HMGB1 has been reported to be
      overexpressed in carboplatin-resistant SKOV3-Carb cells compared with control
      SKOV3 cells. Subsequently, the expression of HMGB1 was silenced by small
      interference RNA technology. Reverse transcription-quantitative polymerase chain
      reaction and western blot analysis indicated that mRNA and protein expression
      levels of HMGB1 were significantly inhibited in HMGB1-silenced cells. Cell
      proliferation and apoptosis analyses were performed to evaluate the effect of
      HMGB1 silencing on resistant ovarian cancer cells. An MTT assay revealed that the
      proliferation of HMGB1-silenced SKOV3 and SKOV3-Carb cells were decreased
      compared with the proliferation of non-silenced control cells. Additionally,
      HMGB1 protein expression levels in SKOV3 cells, but not in SKOV3-Carb cells, were
      decreased in response to carboplatin treatment. Annexin V-fluorescein
      isothiocyanate/propidium iodide staining demonstrated that HMGB1 silencing
      enhanced the effects of carboplatin in inducing the apoptosis of SKOV3-Carb cells
      relative to HMGB1 non-silenced control cells. The results of the present study
      suggested that HMGB1 may be involved in the development of carboplatin resistance
      in ovarian cancer SKOV3 cells and that HMGB1 silencing may induce the
      sensitization of carboplatin-resistant ovarian cancer cells to carboplatin.
      Therefore, HMGB1 may be considered as a potent therapeutic target for increasing
      the sensitivity of ovarian cancer cells to carboplatin in order to improve the
      treatment and prognosis of ovarian cancer.

PMID- 30214594
TI  - Long non-coding RNA-CCAT2 promotes the occurrence of non-small cell lung cancer
      by regulating the Wnt/beta-catenin signaling pathway.
AB  - The present study aimed to investigate the biological function of colon cancer
      associated transcript 2 (CCAT2) in the occurrence and progression of non-small
      cell lung carcinoma (NSCLC) and its potential use in the early diagnosis and
      molecular-targeted therapy of NSCLC. The tumor tissues, para-carcinoma tissues
      and associated clinical data of 36 patients with NSCLC were collected in order to
      detect the expression of CCAT2 and assess the impact of factors including
      histopathological type, Tumor-Node-Metastasis stage and lymph node metastasis on
      CCAT2 expression. The lung cancer NCI-H1975 cell line was transfected with a
      small interfering RNA (siRNA) plasmid to determine the effect of si-CCAT2 on
      NSCLC proliferation, invasion and metastasis. The effect of si-CCAT2 on the
      expression of nuclear and cytoplasmic beta-catenin protein in the lung cancer NCI
      H1975 cell line was detected using western blot analysis. The expression levels
      of CCAT2 in the tumor tissues of patients with NSCLC were significantly higher
      than those in the normal para-carcinoma tissues (t=8.580, P<0.01). Subsequent to
      CCAT2 silencing, the proliferation and invasive abilities of NCI-H1975 cells were
      significantly decreased compared with control cells (P<0.05). In the si-CCAT2
      group, the level of nuclear and cytoplasmic beta-catenin proteins was decreased,
      and the activity of the Wnt signaling pathway was significantly inhibited
      compared with the control cells (P<0.01), and a synergistic effect was exerted
      with the Wnt signaling inhibitor FH535. CCAT2 may therefore promote the
      occurrence of NSCLC by regulating the Wnt/beta-catenin signaling pathway.

PMID- 30214595
TI  - Texture features and pharmacokinetic parameters in differentiating benign and
      malignant breast lesions by dynamic contrast enhanced magnetic resonance imaging.
AB  - Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has become a
      powerful tool for the diagnosis of breast cancer in the clinical setting due to
      its high sensitivity and specificity. Pharmacokinetic parameters, including
      Ktrans and area under the curve (AUC), and texture features derived from DCE-MRI
      have been used to specify the characteristics inside tumors. In the present
      study, 56 patients (average age 45.3+/-11.1; range 25-69 years) with
      histopathologically proved breast tumors were analyzed using the pharmacokinetic
      parameters and texture features. Malignant tumors displayed higher Ktrans and AUC
      values than the benign, Ktrans exhibited a significantly difference between the
      malignant and benign tumors (P=0.001) compared with the AUC values (P=0.029);
      texture features from DCE-MRI images and pharmacokinetic parameter maps also
      showed a good diagnostic ability. Alongside the routine method, principal
      components analysis (PCA) and Fisher discriminant analysis (FDA) were employed on
      these texture features to differentiate the breast lesions automatically. The
      Factor-1 scores of PCA were used to divide the patients into two groups, and the
      diagnosing accuracies of the FDA method on the texture features from DCE-MRI
      images, Ktrans maps, AUC maps were 93, 98 and 98%, with a cross validation
      accuracies of 82, 77 and 77%, respectively. To conclude, pharmacokinetic
      parameters, texture features and the combined computer-assisted classification
      method were discussed. All method involved in this study may be a potential
      assisted tool for radiological analysis on breast.

PMID- 30214596
TI  - Clinical use of trastuzumab combined with different chemotherapy regimens in
      multi-line treatment of advanced human epidermal growth factor receptor 2
      positive gastric cancer: A case report.
AB  - It is generally acknowledged that gastric cancer requires comprehensive treatment
      approaches to be adopted. For patients with human epidermal growth factor
      receptor-2 (HER2)-overexpressing gastric cancer, targeting HER2 with trastuzumab
      in first-line therapy combined with standard chemotherapy significantly improves
      the prognosis. However, there is a lack of international guidance for second-line
      treatment if a patient experiences disease progression. There is also no accepted
      conclusion regarding the efficiency of cross-line therapy with trastuzumab. The
      present study reports the case of a 55-year-old male with gastric cancer who
      underwent radical gastrectomy. Immunohistochemistry indicated that samples were
      EGFR(+) and HER-2(3+), with Ki-67 (20%). From abdominal computed tomography
      scanning and contrast-enhanced ultrasound following surgery, hepatic metastasis
      was identified and the patient was administered microwave thermocoagulation
      therapy. Since December 2012, the patient received multi-line chemotherapy
      regimens as follows: i) Oxaliplatin, tegafur/gimeracil/oteracil and trastuzumab;
      ii) paclitaxel liposome and S-1 plus trastuzumab; iii) apatinib; iv)
      epirubicin/oxaliplatin/xeloda; and v) irinotecan plus trastuzumab. During the
      course of therapy, the trastuzumab served an important function in multi-line
      therapy and the patient benefited from the combined therapy. The application of
      trastuzumab in the multi-line treatment of a patient with HER2-positive advanced
      gastric cancer may be worthy of investigation for use in the clinic.

PMID- 30214597
TI  - Long non-coding RNA AB007962 is downregulated in gastric cancer and associated
      with poor prognosis.
AB  - A number of previous studies have reported that numerous long non-coding RNAs
      (lncRNAs) are dysregulated in gastric cancer (GC) and are involved in a series of
      biological and pathological processes. Total RNA was extracted from the cancerous
      tissues and matched normal adjacent tissues (NATs) of 96 patients with GC. The
      expression level of AB007962, a novel lncRNA, was determined by reverse
      transcription-quantitative polymerase chain reaction. The association between
      AB007962 expression levels and clinicopathological features were analyzed. Kaplan
      Meier curves were also constructed in order to evaluate prognosis. Finally,
      publicly accessible data from The Cancer Genome Atlas was used to further verify
      the expression levels and clinical significance of AB007962. In conclusion, it
      was determined that the expression level of AB007962 was significantly reduced,
      compared with matched NATs in GC tissues (P=0.003). Survival analysis indicated
      that patients with intestinal-type GC with a reduced expression of AB007962 had a
      reduced prognosis, compared with those with an increased expression. AB007962 may
      be involved in the progression of GC and act as a novel prognostic biomarker for
      patients with GC, particularly in intestinal-type GC.

PMID- 30214598
TI  - Neurological manifestations of atrial myxoma: A retrospective analysis.
AB  - Atrial myxoma is the most common type of primary cardiac tumor and it is closely
      associated with stroke in adults. Early diagnosis and treatment of atrial myxomas
      is essential for the prevention of embolic events. The aim of the present study
      was to assess neurological complications associated with atrial myxoma. The
      neurological signs of atrial myxoma were retrospectively assessed in individuals
      who underwent treatment at West China Hospital (Chengdu, China) and The
      Affiliated Hospital of Hainan Medical University (Haikou, China), between March
      2003 and February 2015. A total of 130 patients with atrial myxoma were included
      and 22 (17%) exhibited neurologic signs. These patients were aged 39.9+/-12.6
      years (range, 13-78 years) and there were 13 female and 9 male patients. Ischemic
      cerebral infarct constituted the dominant clinical symptom (68.2%) and 3 patients
      exhibited concomitant cardiac manifestations. Atrial myxoma was diagnosed by
      echocardiography in all patients. Irregular surface of atrial myxomas was
      associated with a high risk of embolic events. The patients with myxoma
      successfully underwent surgery with no mortality recorded. In conclusion, atrial
      myxomas frequently manifest as cerebral infarction in individuals without
      cardiovascular risk factors. These tumors more commonly affect the middle
      cerebral artery. Irregular surface of myxomas appears to be associated with
      embolic events. Echocardiography may improve the diagnosis and early treatment of
      atrial myxomas.

PMID- 30214599
TI  - Intratibial injection of patient-derived tumor cells from giant cell tumor of
      bone elicits osteolytic reaction in nude mouse.
AB  - There have been various reports in the literature of an in vivo model for giant
      cell tumor of bone (GCTB). However, few suitable animal models of GCTB have been
      established, due to the fact that GCTB contains three histologically different
      cell types. To the best of our knowledge, injection of patient-derived GCTB cells
      into bone environment has not been reported until now. In the present study, the
      biological behavior of GCTB cells in nude mice was investigated through
      intratibial injection of patient-derived GCTB cells. Patient-derived GCTB cells
      were obtained from 5 patients who had not undergone chemo- and radiotherapy. Once
      isolated, the cell suspension was injected into the tibias of nude mice. The
      growth process was monitored by weekly observation and photographic documentation
      using X-ray. Four months after injection, nude mice were sacrificed and the
      injected tibial samples were fixed, and further analyzed using micro-computed
      tomography (micro-CT), standard histology, tartrate-resistant acid phosphatase
      (TRAP) staining and mitochondrial immunofluorescence staining. X-ray, micro-CT
      and standard histology revealed osteolytic destruction in the proximal end of the
      tibia. TRAP staining identified TRAP-positive, osteoclast-like cells distributed
      in the bone marrow interface of the lesion area. Anti-human mitochondrial
      immunofluorescence staining confirmed that the surviving cells in the osteolytic
      destruction were of human GCTB cell origin. These findings indicate that
      intratibial injection of patient-derived GCTB cells may elicit osteolytic
      destruction in nude mice. The results of the current study present a novel animal
      model for GCTB, opening new perspectives to investigate this disease and develop
      therapeutic agents.

PMID- 30214600
TI  - Comparison of spatial chromosomal organization between bone marrow and peripheral
      blood in acute myeloid leukemia.
AB  - Acute myeloid leukemia associated with t(8;21)(q22;q22)/runt related
      transcription factor (RUNX)1-RUNX1 translocation partner 1 has been reported to
      exhibit a favorable outcome. The quantitative polymerase chain reaction is a
      reliable method for assessing minimal residual disease persistence, and
      peripheral blood (PB) samples are as informative as bone marrow (BM) samples
      during follow-up monitoring. However, few studies have compared the spatial
      organization of leukemia-specific chromosomes between BM and PB. In the present
      study, paired BM and PB samples were extracted from 6 patients with acute myeloid
      leukaemia-M2 and compared using three-dimensional fluorescence in situ
      hybridization. Cells were classified into three types: Normal, proximal and
      malignant. Comparisons of proportions (% of all cells) of different cell types
      revealed no significant difference between BM and PB samples. The relative radial
      positions (RRPs; d/R) of chromosomes 8 and 21 were consistent for 2/3 of BM and
      PB samples. The RRPs of chromosomes in proximal pairs were more interior in
      nuclei compared with chromosomes in normal pairs for BM and PB samples. The
      consistency of the spatial organization of chromosomes between BM and PB suggests
      that PB may be an alternative to BM for research and clinical diagnosis.

PMID- 30214601
TI  - Chaetominine induces cell cycle arrest in human leukemia K562 and colon cancer
      SW1116 cells.
AB  - Chaetominine is a cytotoxic alkaloid that has been demonstrated to promote
      apoptotic cell death in human leukemia K562 cells. In the present study,
      chaetominine inhibited K562 (IC50 34 nM) and SW1116 (IC50 46 nM) cell growth.
      However, it remains unclear whether the inhibition of cell growth is associated
      with the cell cycle. To assess this potential relationship, the effect of
      chaetominine on the cell cycle of K562 and SW1116 cells was examined.
      Chaetominine treatment caused cell apoptosis and G1-phase arrest in SW1116 cells.
      Conversely, K562 cells underwent S-phase arrest according to flow cytometric
      analysis. The present study also aimed to elucidate the molecular mechanisms
      underpinning cell cycle regulation following the incubation of the associated
      cells with chaetominine. Western blot and reverse transcription-quantitative
      polymerase chain reaction analyses suggested that chaetominine treatment
      facilitated the expression of p53, p21, checkpoint kinase 2 (Chk2) and
      phosphorylated ataxia telangiectasia mutated (p-ATM) and caused a reduction in
      the mRNA levels of cyclin E and cyclin-dependent kinases (CDKs) 2 and 4. These
      results suggest that chaetominine may be involved in the regulation of p53/p21
      and ATM and Rad3-related (ATM)/Chk2 signaling in SW1116 cells. Previous studies
      have demonstrated that these signaling pathways are responsible for G1-phase
      arrest. Results of the present study demonstrated that the expression of p-ATR
      and Chk1 were increased in K562 cells. Additionally, cdc25A levels were
      decreased, while protein and gene expression levels of cyclin A and CDK2 were
      repressed. These results elucidated the role of chaetominine in in the regulation
      of ATR/cdc25A/Chk1 expression in K562 cells. These proteins are thus important
      determinants in the initiation of S-phase arrest. These data support the
      hypothesis that chaetominine is a potential anti-cancer therapeutic agent that
      targets the cell cycle.

PMID- 30214602
TI  - Determination of the prognostic value of preoperative CA15-3 and CEA in
      predicting the prognosis of young patients with breast cancer.
AB  - To the best of our knowledge, no previous study has investigated the association
      of carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) with the
      prognosis for young patients (<=40 years) with breast cancer. In the present
      study, preoperative CEA and CA15-3 serum levels were evaluated in the prediction
      of the prognosis for young patients with breast cancer. In total, 699 patients
      were recruited, for which the CEA and CA15-3 serum levels had been measured prior
      to surgery via a blood sample. The optimal cut-off high and low values were
      determined using receiver operating characteristic curve analysis and Youden's
      index. The value of CEA and CA15-3 in predicting overall survival (OS) and
      disease-free survival (DFS) were measured using univariate and multivariate Cox's
      regression analyses. The cut-off values were 3.38 ng/ml and 12.32 U/ml for CEA
      and CA15-3, respectively. It was identified that CEA, but not CA15-3, was a
      predictor for the prognosis of the young patients with breast cancer.
      Multivariate analysis confirmed that CEA, but not CA15-3, was an independent
      prognostic marker for all young patients with breast cancer. In total, 623 young
      patients exhibited decreased levels of CEA; in these patients, CA15-3 with a cut
      off value of 12.48 U/ml was an independent prognostic factor for OS and DFS.
      Preoperative serum CEA may thus serve as an independent predictor of poor
      prognosis for young patients with breast cancer. However, for low-risk patients
      with decreased CEA levels, serum CA15-3 may supplement the prediction of overall
      prognosis.

PMID- 30214603
TI  - Thiopurine methyltransferase activity in children with acute myeloid leukemia.
AB  - Activity of the enzyme thiopurine methyltransferase (TPMT) determines the anti
      leukemic effect of thiopurines used in the chemotherapy of acute lymphoblastic
      leukemia (ALL) and acute myeloblastic leukemia (AML). TPMT status and its effects
      on treatment outcome have been studied extensively in ALL and autoimmune
      disorders, but few data is available on TPMT in AML. The present study assessed
      the genetic polymorphisms and activity of TPMT in children with AML at different
      treatment stages, and compared the results with those obtained for children with
      ALL. The study included 33 children with AML (0.7-19.7 years) treated with 6
      thioguanine (6-TG) according to the AML-BFM 2004 Protocol. Blood samples were
      collected at diagnosis, during and following maintenance chemotherapy from 8, 10
      and 17 patients with AML (the assay was performed at two time points in 2
      patients), respectively. Blood samples from 105 children with ALL were obtained
      at diagnosis, during the maintenance chemotherapy and following the cessation of
      the chemotherapy from 16, 55 and 34 children, respectively. The activity of TPMT
      in red blood cells lysates was measured using an enzymatic reaction based on the
      conversion of 6-mercaptopurine into 6-methylmercaptopurine, involving S-adenozyl
      L-methionine as the methyl group donor. TPMT mutations were determined using a
      polymerase chain reaction/restriction fragment length polymorphism method. Median
      TPMT activity at diagnosis, during maintenance chemotherapy and following
      chemotherapy was 43.1, 47,3 and 41.7 nmol 6-mMP g-1 Hb h-1, respectively. All
      patients with AML exhibited the homozygous TPMT*1/*1 genotype, with the exception
      of 1, who was a heterozygote with the TPMT*1/*3C genotype and demonstrated a TPMT
      activity level at diagnosis of 42.5 nmol 6-mMP g-1 Hb h-1. At each chemotherapy
      stage, the median TPMT activities in children with AML were significantly
      increased compared with the median TPMT activities in children with ALL. The
      preliminary results suggest that the TPMT activity in AML may be increased
      compared with that in ALL. Comprehensive studies on the association between
      thiopurine metabolism and treatment outcome in AML are required, with regard to
      the cytogenetic and molecular factors currently used for AML risk stratification.

PMID- 30214604
TI  - Toll-like receptor agonist rMBP-NAP enhances antitumor cytokines production and
      CTL activity of peripheral blood mononuclear cells from patients with lung
      cancer.
AB  - Toll-like receptor (TLR) agonists are known for their ability to inhibit tumor
      progression via enhancing antitumor cytokines production and cytotoxic T
      lymphocyte (CTL) activity. Recombinant Helicobacter pylori neutrophil-activating
      protein fused with maltose-binding protein (rMBP-NAP) has been reported as a
      novel TLR agonist for antitumor treatment in murine models. The present study
      aimed to determine the potential and efficacy of the rMBP-NAP for antitumor
      treatment prior to further clinical trials. The rMBP-NAP was expressed and
      purified for subsequent experiments. Peripheral blood mononuclear cells (PBMCs)
      from health donors and patients with lung cancer (LC) were incubated with PBS and
      0.2 mg/ml rMBP-NAP. Antitumor cytokines production was assayed using ELISA and
      reverse transcription-quantitative polymerase chain reaction analysis. The
      cytolytic activity of PBMCs and the number of Interferon-gamma (IFN-gamma)
      secreting cells were assayed using lactate dehydrogenase and Enzyme-linked
      ImmunoSpot assays, respectively. The results from the present study revealed that
      the expression of IFN-gamma, interleukin (IL)-2, tumor necrosis factor-alpha and
      IL-12 of PBMCs from patients with LC and healthy donors were significantly
      increased following treatment with rMBP-NAP (P<0.05). Additionally, rMBP-NAP
      significantly upregulated the number of IFN-gamma-secreting cells in PBMCs and
      prominently increased the cytotoxic activity of PBMCs (P<0.05). Furthermore, the
      expression of TLR2 was significantly enhanced following rMBP-NAP stimulation
      (P<0.05), which indicated that rMBP-NAP may serve an antitumor role via TLR2
      signaling pathways. Overall, these results demonstrated that rMBP-NAP possesses
      the potential to be a novel immunomodulatory candidate drug and requires further
      evaluation in clinical trials.

PMID- 30214605
TI  - Detection of copy number variants and loss of heterozygosity from impure tumor
      samples using whole exome sequencing data.
AB  - Using whole-exome sequencing (WES) for the detection of chromosomal aberrations
      from tumor samples has become increasingly popular, as it is cost-effective and
      time efficient. However, factors which present in WES tumor samples, including
      diversity in exon size, batch effect and tumor impurity, can complicate the
      identification of somatic mutation in each region of the exon. To address these
      issues, the authors of the present study have developed a novel method, PECNV,
      for the detection of genomic copy number variants and loss of heterozygosity in
      WES datasets. PECNV combines normalized logarithm ratio of read counts (Log
      Ratio) and B allele frequency (BAF), and then employs expectation maximization
      (EM) algorithm to estimate parameters involved in the models. A comprehensive
      assessment of PECNV of PECNV was performed by analyzing simulated datasets
      contaminated with different normal cell proportion and eight real primary triple
      negative breast cancer samples. PECNV demonstrated superior results compared with
      ExomeCNV and EXCAVATOR for the detection of genomic aberrations in WES data.

PMID- 30214606
TI  - IRE1alpha-XBP1 signaling pathway regulates IL-6 expression and promotes
      progression of hepatocellular carcinoma.
AB  - Of the three unfolded protein response pathways, which are activated by
      endoplasmic reticulum stress, inositol-requiring enzyme 1alpha (IRE1alpha)-X-box
      binding protein 1 (XBP1) signaling is the most conserved. These pathways are
      implicated in a variety of types of cancer, including hepatocellular carcinoma
      (HCC). However, the role of IRE1alpha-XBP1 signaling in the development of HCC
      remains unclear. In the current study, reverse transcription-quantiative
      polymerase chain reaction was used to analyze the expression levels of XBP1 and
      interleukin (IL)-6 in human tissues and cells. ChIP and luciferase reporter
      assays were utilized to investigate the interaction between XBP1s and IL-6
      promoter DNA. It was revelaed that IRE1alpha-XBP1 signaling promotes the
      proliferation of HCC cells via regulating hepatic IL-6 expression. It was
      observed that the splicing levels of XBP1 and hepatic IL-6 content were increased
      and positively correlated with each other in human HCC tissues (r2=0.5846,
      P=0.004). Ectopic expression of IRE1alpha or XBP1s increased IL-6 levels in LO2
      and Hep3B cells. In addition, pharmacological inhibition of IRE1alpha reduced the
      levels of IL-6 expression and secretion through blocking the generation of XBP1s,
      which bound directly to the IL-6 promoter and activated its expression. Further
      investigation demonstrated that IL-6 driven by XBP1s was secreted outside of
      cells and activated signal transducer and activator of transcription 3 (STAT3)
      signaling in an autocrine/paracrine manner, to regulate the proliferation of
      Hep3B cells. Blockage of IL-6-STAT3 signaling with tocilizumab attenuated the
      effect of IRE1alpha-XBP1 signaling in promoting Hep3B cell proliferation. In
      conclusion, the present study revealed that IRE1alpha-XBP1 signaling promotes
      carcinogenesis of HCC by regulating the activation of the IL-6-STAT3 signaling
      pathway.

PMID- 30214607
TI  - Glucosamine decreases the stemness of human ALDH+ breast cancer stem cells by
      inactivating STAT3.
AB  - Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for
      tumor maintenance and relapse due to their ability to resist various anticancer
      effects. Owing to the resistance of CSCs to the effects of targeted therapy, an
      alternative strategy that targets post-translational glycosylation may be an
      improved approach to treat cancer as it disrupts multiple coordinated signaling
      that maintains the stemness of CSCs. Glucosamine acts as an anticancer agent
      possibly by inhibiting N-linked glycosylation. The aim of the present study was
      to investigate the effect of glucosamine on the stemness of breast CSCs, which is
      regulated by signal transducer and activator of transcription 3 (STAT3)
      signaling. Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7
      cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine
      for 24 h. Subsequently, cell viability was determined by performing a trypan blue
      exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer
      binding transcription factor 4 (OCT-4), and Kruppel-like factor 4 (KLF4)]
      expression was determined using the reverse transcription-quantitative polymerase
      chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were
      determined by performing western blot analysis. Furthermore, the number of
      mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was
      determined. It was determined that glucosamine treatment decreased the viability
      of ALDH+ breast CSCs. Glucosamine treatment also decreased the stemness of ALDH+
      breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4
      expression level, and a decreased number of MFUs. This effect of glucosamine may
      be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine
      inhibited STAT3 activation; therefore, the results of the present study indicated
      that glucosamine treatment may be an improved approach to target the stemness of
      CSCs.

PMID- 30214608
TI  - The function of FAK/CCDC80/E-cadherin pathway in the regulation of B16F10 cell
      migration.
AB  - Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in the
      development and progression of cancer. However, the regulatory role of FAK in
      cell migration remains unclear. The aim of the present study was to investigate
      the mechanism underlying the regulation of melanoma cell migration by FAK. The
      effect of FAK knockdown on gene expression in B16F10 cells was examined by gene
      chip analysis. The expression levels of coiled-coil domain containing 80 (CCDC80)
      and epithelial (E)-cadherin were analyzed by reverse transcription quantitative
      polymerase chain reaction and western blotting. Wound healing and transwell
      assays were used to monitor B16F10 cell migration. It was identified that the
      knockdown of FAK increased the expression levels of CCDC80 and E-cadherin, while
      the overexpression of CCDC80 elevated E-cadherin expression. Concurrently,
      upregulation of CCDC80 inhibited the migration of B16F10 cells, and
      downregulation of CCDC80 promoted the migration of B16F10 cells. The clinical
      data from the Oncomine database also revealed that the mRNA level of FAK was
      increased while the mRNA levels of CCDC80 and E-cadherin were decreased in
      patients with melanoma compared with normal controls. Taken together, the results
      of the present study suggest that the regulation of B16F10 melanoma cell
      migration by FAK is potentially mediated by CCDC80.

PMID- 30214609
TI  - Gefitinib induces non-small cell lung cancer H1650 cell apoptosis through
      downregulating tumor necrosis factor-related apoptosis-inducing ligand expression
      levels.
AB  - Non-small cell lung cancer (NSCLC) presents severe threats to the lives of
      patients. Gefitinib is one of the first-line drugs available for the treatment of
      NSCLC in the clinical setting. The present study investigated the effects of
      gefitinib on NSCLC H1650 cell viability and apoptosis via MTT assays and flow
      cytometry. Western blot analysis was employed to detect tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) expression levels in H1650 cells. In
      the present study, H1650 cells were treated with TRAIL siRNA or an empty plasmid
      vector control, followed by gefitinib treatment to investigate apoptosis.
      Gefitinib treatment markedly inhibited H1650 cell viability, induced apoptosis
      and reduced TRAIL expression levels. TRAIL interference enhanced H1650 cell
      apoptosis induced by gefitinib. TRAIL overexpression suppressed gefitinib-induced
      H1650 cell apoptosis. In addition, gefitinib induced NSCLC H1650 cell apoptosis
      by downregulating TRAIL expression levels.

PMID- 30214611
TI  - Erratum: Downregulation of ubiquitin-specific peptidase 39 suppresses the
      proliferation and induces the apoptosis of human colorectal cancer cells.
AB  - [This corrects the article DOI: 10.3892/ol.2018.8061.].

PMID- 30214610
TI  - Evaluation of the mRNA expression levels of integrins alpha3, alpha5, beta1 and
      beta6 as tumor biomarkers of oral squamous cell carcinoma.
AB  - Integrin signaling may modulate several different functions involved in cell
      migration, invasion, proliferation and motility, and is a potential candidate
      biomarker for oral cancer. In the present study, a total of four integrin genes
      were evaluated as potential biomarkers of oral squamous cell carcinoma (OSCC).
      Gene expression was determined using the reverse transcription-quantitative
      polymerase chain reaction in 55 OSCC and 55 matched normal oral tissues. The
      performance of individual and combined biomarkers was analyzed by receiver
      operating characteristic (ROC) analysis based on the relative mRNA expression
      (OSCC vs. matched oral tissue from the tumor-free margin), which was calculated
      using the DeltaDeltaCq value (DeltaCq of OSCC-DeltaCq of oral tissue from the
      tumor-free margin of the same patient). In the individual ROC analysis, the areas
      under the ROC curve (AUCs) of relative mRNA expression (DeltaDeltaCq) of integrin
      subunit alpha3 (ITGA3), integrin subunit alpha5 (ITGA5), integrin subunit beta1
      (ITGB1) and integrin subunit beta6 (ITGB6) in all tumor locations were 0.724,
      0.698, 0.640 and 0.657, respectively. For locations 2 (tongue/mouth part) and 3
      (edentulous ridge), their individual AUC values were 0.840, 0.765, 0.725 and
      0.763, respectively. In the cumulative ROC analysis, ITGA3, ITGA5 and ITGB1 genes
      exhibited the highest combined AUC values (0.809 and 0.871 for all locations and
      locations 2 and 3 combined, respectively) compared with other biomarker
      combinations. In conclusion, the results of the present study identified that
      higher mRNA expressions of ITGA3, ITGA5, ITGB1 and ITGB6 genes are suitable for
      OSCC diagnosis biomarkers. Cumulative ROC analysis indicated an improved overall
      performance compared with the best individual integrin biomarker of OSCC.

PMID- 30214612
TI  - Adjuvant transarterial chemoembolization to improve the prognosis of
      hepatocellular carcinoma following curative resection.
AB  - The present study aimed to investigate the prognostic factors for recurrence of
      hepatocellular carcinoma (HCC) following curative resection, and evaluate the
      efficacy of postoperative adjuvant transarterial chemoembolization (TACE) in
      improving prognosis. A total of 166 patients who underwent curative resection
      followed by adjuvant TACE, and 190 patients who underwent curative resection
      alone were studied retrospectively. Univariate and multivariate analyses were
      performed to investigate the risk factors of recurrence. Separated based on risk
      factors, subgroup studies were conducted and the association between TACE and
      recurrence rates was examined. Postoperative overall survival rates were
      determined using the Kaplan-Meier method and differences between the two
      therapeutic strategies were identified through log-rank analysis. Computerized
      tomography (CT)/magnetic resonance imaging (MRI) images were used to evaluate the
      function of postoperative adjuvant TACE for enhancing the efficacy of CT/MRI in
      detecting recurrence. The results of the univariate and multivariate analyses
      revealed that tumor capsule invasion, vascular invasion, and multiple nodules
      were risk factors of early recurrence. For patients with these risk factors,
      recurrence rates were markedly decreased at 6 and 12 months, but not at 18 and 24
      months, if TACE was added to curative resection. The hepatitis B virus (HBV) was
      a risk factor for late recurrence. Postoperative TACE was not effective in
      reducing the recurrence rate in patients with HBV. Survival increased following
      curative resection with TACE compared with curative resection alone. Furthermore,
      adjuvant TACE enhanced the efficacy of CT/MRI in detecting recurrence.
      Postoperative adjuvant TACE may improve the prognosis of HCC following curative
      resection.

PMID- 30214613
TI  - Expression of Livin and PlGF in human osteosarcoma is associated with tumor
      progression and clinical outcome.
AB  - Baculoviral IAP repeat containing 7 (BIRC7/Livin/ML-IAP/KIAP; referred to as
      Livin throughout the present study) and placental growth factor (PlGF) are not
      detectable in the majority of normal differentiated tissues, but are present in a
      number of types of cancer, including hepatocellular carcinoma, ovarian cancer and
      renal cell carcinoma. The aim of the present study was to assess the expression
      levels of Livin and PlGF in human osteosarcoma specimens and cell lines, and to
      analyze the functions of Livin and PIGF in the prognosis of osteosarcoma. The
      expression levels of Livin and PlGF in 48 osteosarcoma specimens and three
      osteosarcoma cells were determined using immunohistochemistry and reverse
      transcription-quantitative polymerase chain reaction. The positivity rates of
      Livin and PlGF in osteosarcoma specimens were 58.3 and 60.4%, respectively, but
      were 0% in normal bone tissues. The expression levels of Livin and PlGF were
      increased in MG-63 cells, compared with those in the other cell lines evaluated
      in the present study. In addition, the expression levels of Livin and PlGF were
      significantly associated with tumor diameter and Enneking staging, but were
      independent of tumor site, age and sex of patients. The expression level of Livin
      was not associated with PlGF. Furthermore, the 5-year overall survival rate was
      decreased in the Livin or PlGF expression group, compared with that in the non
      expression group (P=0.034 and P=0.012, respectively). The expression levels of
      Livin and PlGF were independent prognostic factors for patients with
      osteosarcoma. The results of the present study demonstrated that Livin and PlGF
      may participate in the pathogenesis of osteosarcoma. Therefore, pharmacological
      inhibition of Livin or PlGF may provide a novel strategy for osteosarcoma
      treatment.

PMID- 30214614
TI  - Integrated bioinformatic analysis of microarray data reveals shared gene
      signature between MDS and AML.
AB  - Myeloid disorders, especially myelodysplastic syndrome (MDS) and acute myeloid
      leukemia (AML), cause significant mobility and high mortality worldwide. Despite
      numerous attempts, the common molecular events underlying the development of MDS
      and AML remain to be established. In the present study, 18 microarray datasets
      were selected, and a meta-analysis was conducted to identify shared gene
      signatures and biological processes between MDS and AML. Using NetworkAnalyst,
      191 upregulated and 139 downregulated genes were identified in MDS and AML, among
      which, PTH2R, TEC, and GPX1 were the most upregulated genes, while MME, RAG1, and
      CD79B were mostly downregulated. Comprehensive functional enrichment analyses
      revealed oncogenic signaling related pathway, fibroblast growth factor receptor
      (FGFR) and immune response related events, 'interleukine-6/interferon signaling
      pathway, and B cell receptor signaling pathway', were the most upregulated and
      downregulated biological processes, respectively. Network based meta-analysis
      ascertained that HSP90AA1 and CUL1 were the most important hub genes.
      Interestingly, our study has largely clarified the link between MDS and AML in
      terms of potential pathways, and genetic markers, which shed light on the
      molecular mechanisms underlying the development and transition of MDS and AML,
      and facilitate the understanding of novel diagnostic, therapeutic and prognostic
      biomarkers.

PMID- 30214615
TI  - Comparison of redox parameters in ovarian endometrioma and its malignant
      transformation.
AB  - The present study aimed to evaluate the levels of oxidative stress and
      antioxidant markers in benign endometrioma (OE) and its malignant transformation
      [endometriosis-associated ovarian cancer (EAOC)] by measuring 8-hydroxy-2
      deoxyguanosine (8-OHdG), heme oxygenase-1 (HO-1) and total antioxidant capacity
      (TAC/Heme-iron) alterations associated with disease progression. Cyst fluid
      samples from 44 patients with OE and 14 patients with EAOC were studied using an
      enzyme-linked immunosorbent assay. A chi2 test, t-test and Pearson correlation
      test were performed using SPSS version 22.0. The cut-off point, sensitivity and
      specificity of each marker for EAOC diagnosis were evaluated by receiver
      operating characteristic curve analysis. Cyst fluid 8-OHdG and HO-1 levels in the
      EAOC group were significantly decreased compared with the OE subjects (P=0.013
      and P<0.001, respectively). The levels of TAC/Heme-iron in patients with EAOC
      were significantly higher compared with those in the OE subjects (P<0.001). The
      present study demonstrated a positive correlation between 8-OHdG and HO-1 levels
      (P=0.012). HO-1 exhibited the highest discriminant value for EAOC (Area Under the
      Curve=0.901). The optimal cut-off point of HO-1 for the diagnosis of EAOC was
      2.314 ng/ml, with a sensitivity and specifity of 95.2 and 85.7%, respectively.
      The present study revealed a clear separation between the overall redox state in
      OE and EAOC. It was concluded that characteristic alterations in important
      factors in redox may be helpful for understanding the pathogenesis of the
      malignant transformation of endometriosis.

PMID- 30214616
TI  - Increased EZH2 expression during the adenoma-carcinoma sequence in colorectal
      cancer.
AB  - The adenoma-carcinoma sequence, the sequential mutation and deletion of various
      genes by which colorectal cancer progresses, is a well-established and accepted
      concept of colorectal cancer carcinogenesis. Proteins of the polycomb repressive
      complex 2 (PRC2) function as transcriptional repressors by trimethylating histone
      H3 at lysine 27; the activity of this complex is essential for cell proliferation
      and differentiation. The histone methyltransferase enhancer of zeste homolog 2
      (EZH2), an essential component of PRC2, is associated with the transcriptional
      repression of tumor suppressor genes. EZH2 expression has previously been
      reported to increase with the progression of pancreatic intraductal papillary
      mucinous neoplasm. Thus, we hypothesized that EZH2 expression also increases
      during the adenoma-carcinoma sequence of colorectal cancer. The present study
      investigated changes in EZH2 expression during the colorectal adenoma-carcinoma
      sequence. A total of 47 patients with colorectal adenoma, 20 patients with
      carcinoma in adenoma and 43 patients with colorectal carcinoma who underwent
      surgical or endoscopic resection were enrolled in this study. Non-cancerous
      tissue from the clinical specimens was also examined. The association between
      EZH2 expression, pathology and expression of tumor suppressor genes during
      colorectal carcinogenesis were analyzed. Each specimen was immunohistochemically
      stained for EZH2, proliferation marker protein Ki-67 (Ki-67), cyclin-dependent
      kinase inhibitor (CDKN) 1A (p21), CDKN1B (p27) and CDKN2A (p16). Total RNA was
      extracted from formalin-fixed paraffin-embedded blocks and reverse transcription
      quantitative polymerase chain reaction analysis of these genes was performed. Ki
      67 and EZH2 expression scores increased significantly during the progression of
      normal mucosa to adenoma and carcinoma (P=0.009), and EZH2 expression score was
      positively associated with Ki-67 expression score (P=0.02). Conversely, p21 mRNA
      and protein expression decreased significantly, whereas expression of p27 and p16
      did not change significantly. During the carcinogenesis sequence from normal
      mucosa to adenoma and carcinoma, EZH2 expression increased and p21 expression
      decreased significantly. EZH2 may therefore contribute to the development of
      colorectal cancer from adenoma via suppression of p21.

PMID- 30214617
TI  - Identifying miRNA-mRNA regulation network of major depressive disorder in ovarian
      cancer patients.
AB  - Major depression disorder (MDD) has become increasingly common in patients with
      ovarian cancer, which complicates the treatment course. The microRNA (miRNA)-mRNA
      regulation network may help elucidate the potential mechanism of MDD in ovarian
      cancer. The differentially expressed microRNAs (DEmiRs) and mRNAs (DEmRNAs) were
      therefore identified from the GSE61741, GSE58105 and GSE9116 ovarian cancer
      datasets using GEO2R. The target genes of the DEmiRs were then obtained using the
      TargetScan, microRNAorg, microT-CDS, miRDB and miRTarBase prediction tools. The
      DAVID program was used to identify the KEGG pathways of target genes, and the
      core genes of major depressive disorder (MDD) were identified using the Kaplan
      Meier Plotter for ovarian cancer. A total of 5 DEmiRs (miR-23b-3p, miR-33b-3p,
      miR-1265, miR-933 and miR-629-5p) were obtained from GSE61741 and GSE58105. The
      target genes of these DEmiRs were enriched in pathways that were considered high
      risk for developing MDD in ovarian cancer. A total of 11 risk genes were selected
      from these pathways as the core genes in the miRNA-mRNA network of MDD in ovarian
      cancer, and eventually identified the following 12 miRNA-mRNAs pairs: miR-629-5p
      FGF1, miR-629-5p-AKT3, miR-629-5p-MAGI2, miR-933-BDNF, miR-933-MEF2A, miR-23b-3p
      TJP1, miR-23b-3p-JMJD1, miR-23b-3p-APAF1, miR-23b-3p-CAB39, miR-1265-CDKN1B, miR
      33b-3p-CDKN1B, and miR-33b-3p-F2R. These results may provide novel insights into
      the mechanisms of developing MDD in ovarian cancer patients.

PMID- 30214618
TI  - Effects of gene polymorphisms on the risk of severe hyponatremia during DCF
      chemotherapy for patients with esophageal squamous cell carcinoma.
AB  - Combination chemotherapy using docetaxel, cisplatin and 5-fluorouracil (DCF) is a
      promising treatment option for patients with advanced esophageal squamous cell
      carcinoma (ESCC), although its clinical application is limited by severe systemic
      toxicities. There are no validated markers for predicting the adverse effects
      caused by this regimen. This pharmacogenetic study enrolled 57 patients with
      chemotherapy-naive advanced ESCC between July 2012 and March 2016
      (UMIN000008462). All patients received at least one course of DCF chemotherapy
      (docetaxel, 60 mg/m2 on day 1; cisplatin, 70 mg/m2 on day 1; 5-fluorouracil, 600
      mg/m2 on days 1-5). The associations between four gene polymorphisms (ERCC1
      rs11615, GSTP1 rs1695, TYMS rs151264360 and XPD rs13181) and the development of
      grade 3/4 adverse events during the first course of chemotherapy were
      prospectively investigated. The patients had a median age of 66 years (range, 45
      77 years) and the majority were male (51 males vs. 6 females). The treatment
      settings were neoadjuvant (47 patients), adjuvant (1 patient) and salvage (9
      patients), with dose intensities of 100% (51 patients) or 80% (6 patients). The
      severe adverse events were leukopenia (70.2%), neutropenia (86.0%), febrile
      neutropenia (36.8%), acute kidney injury (29.1%) and hyponatremia (43.9%). Two
      polymorphisms were independently associated with the development of severe
      hyponatremia among patients carrying the minor allele (vs. patients with major
      homozygote genotype): TYMS 3'-UTR rs151264360 (odds ratio, 3.64; 95% confidence
      interval, 1.11-11.9) and XPD Lys751Gln rs13181 (odds ratio, 10.1; 95% confidence
      interval, 1.10-93.3). Therefore, the presence of the TYMS and XPD polymorphisms
      may aid in identifying patients with a high risk of developing severe
      hyponatremia during DCF chemotherapy.

PMID- 30214619
TI  - Anti-proliferative and pro-apoptotic effects of rosemary and constituent
      terpenoids in a model for the HER-2-enriched molecular subtype of clinical breast
      cancer.
AB  - Neoadjuvant treatment options for human epidermal growth factor receptor-2 (HER
      2)-enriched and luminal B molecular subtypes of clinical breast cancer include
      HER-2-targeted therapy with chemotherapy or anti-hormonal therapy. These
      treatment options result in systemic toxicity and acquired tumor resistance.
      Minimally toxic naturally occurring phytochemicals may represent testable
      alternatives to conventional therapy. HER-2-overexpressing tumorigenic human
      mammary epithelial 184-B5/HER cells represent a model for the HER-2-enriched
      breast cancer subtype. Non-fractionated rosemary extract (RME) and constituent
      phenolic terpenoids ursolic acid (UA), carnosol (CSOL) and carnosic acid (CA)
      represented the test agents. Anchorage-independent (AI) proliferation, cell cycle
      progression, cellular apoptosis and expression of cell cycle-regulatory and
      apoptosis-specific proteins represented the mechanistic end point biomarkers.
      Relative to the parental non-tumorigenic 184-B5 cells, tumorigenic 184-B5/HER
      cells exhibited decreased population doubling, increased saturation density,
      accelerated cell cycle progression and downregulated cellular apoptosis,
      confirming the loss of homeostatic control of proliferation. Treatment with the
      test agents resulted in a dose-dependent decrease in AI colony number, indicating
      a decrease in cancer risk. Mechanistically, RME and UA inhibited G1-S phase
      transition resulting in an increased G1:S+G2/M ratio and decreased cyclin D1
      expression. The pro-apoptotic effect of RME and UA was indicated by increased sub
      G0 (apoptotic) cell population, and relevant reciprocal modulation, as
      demonstrated by decreased anti-apoptotic B-cell lymphoma-2 (Bcl-2) and increased
      pro-apoptotic Bcl-2-associated X protein expression. In contrast, treatment with
      CA and CSOL resulted in cytostatic G2/M arrest and an increase in cyclin B1
      expression; thus, naturally-occurring rosemary and its constitutive terpenoids re
      establish homeostatic control of proliferation and decrease cancer risk via
      distinct mechanisms. These data validate an experimental approach to prioritize
      efficacious natural compounds as testable alternatives for conventional chemo
      endocrine and HER-2-targeted therapies in HER-2-enriched breast cancer.

PMID- 30214621
TI  - Comparative biodistribution analysis across four different 89Zr-monoclonal
      antibody tracers-The first step towards an imaging warehouse.
AB  - Rationale: Knowledge on monoclonal antibody biodistribution in healthy tissues in
      humans can support clinical drug development. Molecular imaging with positron
      emission tomography (PET) can yield information in this setting. However, recent
      imaging studies have analyzed the behavior of single antibodies only, neglecting
      comparison across different antibodies. Methods: We compared the distribution of
      four 89Zr-labeled antibodies in healthy tissue in a retrospective analysis based
      on the recently published harmonization protocol for 89Zr-tracers and our
      delineation protocol. Results: The biodistribution patterns of 89Zr-lumretuzumab,
      89Zr-MMOT0530A, 89Zr-bevacizumab and 89Zr-trastuzumab on day 4 after tracer
      injection were largely similar. The highest tracer concentration was seen in
      healthy liver, spleen, kidney and intestines. About one-third of the injected
      tracer dose was found in the circulation, up to 15% in the liver and only 4% in
      the spleen and kidney. Lower tracer concentration was seen in bone marrow, lung,
      compact bone, muscle, fat and the brain. Despite low tracer accumulation per gram
      of tissue, large-volume tissues, especially fat, can influence overall
      distribution: On average, 5-7% of the injected tracer dose accumulated in fat,
      with a peak of 19% in a patient with morbid obesity. Conclusion: The similar
      biodistribution of the four antibodies is probably based on their similar
      molecular structure, binding characteristics and similar metabolic pathways.
      These data provide a basis for a prospectively growing, online accessible
      warehouse of molecular imaging data, which enables researchers to increase and
      exchange knowledge on whole body drug distribution and potentially supports drug
      development decisions.

PMID- 30214620
TI  - Imaging and therapy of ovarian cancer: clinical application of nanoparticles and
      future perspectives.
AB  - Despite significant advances in cancer diagnostics and treatment, ovarian cancers
      (OC) continue to kill more than 150,000 women every year worldwide. Due to the
      relatively asymptomatic nature and the advanced stage of the disease at the time
      of diagnosis, OC is the most lethal gynecologic malignancy. The current treatment
      for advanced OC relies on the synergistic effect of combining surgical
      cytoreduction and chemotherapy; however, beside the fact that chemotherapy
      resistance is a major challenge in OC management, new imaging strategies are
      needed to target microscopic lesions and improve both cytoreductive surgery and
      patient outcomes. In this context, nanostructured probes are emerging as a new
      class of medical tool that can simultaneously provide imaging contrast, target
      tumor cells, and carry a wide range of medicines resulting in better diagnosis
      and therapeutic precision. Herein we summarize several exemplary efforts in
      nanomedicine for addressing unmet clinical needs.

PMID- 30214622
TI  - Cholangiocarcinoma therapy with nanoparticles that combine downregulation of
      MicroRNA-210 with inhibition of cancer cell invasiveness.
AB  - Cholangiocarcinoma (CCA) is the second most common primary liver malignancy with
      extremely poor therapeutic outcome due to high drug resistance, widespread
      metastasis and lack of effective treatment options. CCA progression and
      metastasis are regulated by multiple biological factors including multiple miRNAs
      and chemokine receptor CXCR4. The goal of this study was to test if
      nanotherapeutic blockade of CXCR4 by polymeric CXCR4 antagonist (PCX) combined
      with inhibition of hypoxia-inducible miR-210 cooperatively enhances therapeutic
      efficacy in CCA through reducing invasiveness, inducing cell killing, and
      reversing drug resistance. Methods: We first tested the activity of PCX to
      inhibit migration of CCA cells. We then prepared PCX/anti-miRNA nanoparticles and
      analyzed their miRNA delivery efficacy and anticancer activity in vitro. Finally,
      in vivo biodistribution assay and anticancer activity study were performed in CCA
      tumor-bearing mice. Results: Our results show that PCX had a broad inhibitory
      effect on cell migration, effectively delivered anti-miR-210, and downregulated
      miR-210 expression in CCA cells. Combination PCX/anti-miR-210 nanoparticles
      showed cytotoxic activity towards CCA cells and reduced the number of cancer stem
      like cells. The nanoparticles reversed hypoxia-induced drug resistance and
      sensitized CCA cells to standard gemcitabine and cisplatin combination treatment.
      Systemic intravenous treatment with the nanoparticles in a CCA xenograft model
      resulted in prominent combined antitumor activity. Conclusion: Our findings
      support PCX-based nanoparticles as a promising delivery platform of therapeutic
      miRNA in combination CCA therapies.

PMID- 30214623
TI  - Intragland Shh gene delivery mitigated irradiation-induced hyposalivation in a
      miniature pig model.
AB  - Irreversible hypofunction of salivary glands is common in head and neck cancer
      survivors treated with radiotherapy and can only be temporarily relieved with
      current treatments. We found recently in mouse models that transient activation
      of Hedgehog pathway following irradiation rescued salivary gland function by
      preserving salivary stem/progenitor cells, parasympathetic innervation and
      microvessels. Due to huge differences between salivary glands of rodents and
      humans, to examine the translational potential of this approach, we evaluated
      effects of Shh gene transfer in a miniature pig model of irradiation-induced
      hyposalivation. Methods: The right parotid of each pig was irradiated with a
      single dose of 20 Gray. Shh and control GFP genes were delivered into irradiated
      parotid glands by noninvasive retrograde ductal instillation of corresponding
      adenoviral vectors 4 or 16 weeks after irradiation. Parotid saliva was collected
      every two weeks. Parotid glands were collected 5 or 20 weeks after irradiation
      for histology, Western blot and qRT-PCR assays. Results: Shh gene delivery 4
      weeks after irradiation significantly improved stimulated saliva secretion and
      local blood supply up to 20 weeks, preserved saliva-producing acinar cells,
      parasympathetic innervation and microvessels as found in mouse models, and also
      activated autophagy and inhibited fibrogenesis in irradiated glands. Conclusion:
      These data indicate the translational potential of transient activation of
      Hedgehog pathway to preserve salivary function following irradiation.

PMID- 30214624
TI  - Aptamer-functionalized nanoscale metal-organic frameworks for targeted
      photodynamic therapy.
AB  - Photodynamic therapy (PDT) has been applied in clinical cancer treatment. Here we
      report an aptamer-functionalized nanoscale metal-organic framework for targeted
      PDT. Our nanosystem can be easily prepared and successfully used for targeted PDT
      with a significantly enhanced therapeutic efficacy in vitro and in vivo. Methods:
      By combining the strong binding ability between phosphate-terminated aptamers and
      Zr-based nanoscale metal-organic frameworks (Zr-NMOFs) and the intercalation of
      photosensitizer TMPyP4 within the G-quadruplex DNA structure, TMPyP4-G4-aptamer
      NMOFs were prepared. The characteristics and photodynamic performance of TMPyP4
      G4-aptamer-NMOFs were examined after preparation. Then, we studied their
      stability, specific recognition ability, and phototoxicity in vitro. For in vivo
      experiments, the nanosystem was intratumorally injected into a HeLa subcutaneous
      xenograft tumor mouse model. After irradiation on day 0, mice were further
      injected with the nanosystem on day 5 and were again subjected to laser
      irradiation for 30 min. Tumor volumes and body weights of all mice were measured
      by caliper every 2 days after the treatment. Results: The nanosystem induced 90%
      cell death of targeted cells. In contrast, the control cells maintained about 40%
      cell viability at the same concentration of nanosystem. For the in vivo
      experiments, the nanosystem-treated group maintained more than 76% inhibition
      within the entire experimental period. Conclusion: We have demonstrated that our
      smart TMPyP4-G4-sgc8-NMOFs nanosystem can be used for targeted cancer therapy
      with high efficiency.

PMID- 30214625
TI  - Transcriptomic signature associated with carcinogenesis and aggressiveness of
      papillary thyroid carcinoma.
AB  - Papillary thyroid carcinoma (PTC) is the fastest-growing disease caused by
      numerous molecular alterations in addition to previously reported DNA mutations.
      There is a compelling need to identify novel transcriptomic alterations that are
      associated with the pathogenesis of PTC with potential diagnostic and prognostic
      implications. Methods: We gathered and compared 242 expression profiles between
      paired PTC and adjacent normal tissues and identified and validated the coding
      and long non-coding RNAs (lncRNAs) associated with the extrathyroidal extension
      (ETE) of 655 PTC patients in two independent cohorts, followed by predicting
      their interactions with drugs. Co-expression, RNA interaction, Kaplan-Meier
      survival and multivariate Cox proportional regression analyses were performed to
      identify dysregulated lncRNAs and genes that correlated with clinical outcomes of
      PTC. Alternative splicing (AS), RNA circularization, and editing were also
      compared between transcriptomes to expand the repertoire of molecular alterations
      in PTC. Results: Numerous genes related to cellular microenvironment and steroid
      hormone response were associated with the ETE of PTC. Drug susceptibility
      predictions of the expression signature revealed two highly ranked compounds, 6
      bromoindirubin-3'-oxime and lovastatin. Co-expression and RNA interaction
      analysis revealed the essential role of lncRNAs in PTC pathogenesis by modulating
      extracellular matrix and cell adhesion. Eight genes and two novel lncRNAs were
      identified that correlated with the aggressive nature and disease-free survival
      of PTC. Furthermore, this study provided the transcriptome-wide landscape of
      circRNAs in PTC and uncovered dissimilar expression profiles among circRNAs
      originating from the same host gene, suggesting the functional complexity of
      circRNAs in PTC carcinogenesis. The newly identified AS events in the SERPINA1
      and FN1 genes may improve the sensitivity and specificity of these diagnostic
      biomarkers. Conclusions: Our study uncovered a comprehensive transcriptomic
      signature associated with the carcinogenesis and aggressive behavior of PTC, as
      well as presents a catalog of 10 potential biomarkers, which would facilitate PTC
      prognosis and development of new therapeutic strategies for this cancer.

PMID- 30214626
TI  - Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses
      NPM1-mutated leukemic cell survival.
AB  - Acute myeloid leukemia (AML) with an NPM1 mutation (NPMc+) has a distinct gene
      expression signature and displays molecular abnormalities similar to mixed
      lineage leukemia (MLL), including aberrant expression of the PBX3 and HOXA gene
      cluster. However, it is unclear if the aberrant expression of PBX3 and HOXA is
      essential for the survival of NPM1-mutated leukemic cells. Methods: Using the
      gene expression profiling of TCGA and E-MTAB-3444 datasets, we screened for high
      co-expression of PBX3 and HOXA9 in NPMc+ leukemia patients. We performed NPMc+
      depletion and overexpression experiments to examine aberrant H3K79 methylation
      through epigenetic regulation. Through RNA interference technology and small
      molecule inhibitor treatment, we evaluated the effect of methyl-modified H3K79 on
      cell survival and explored the possible underlying mechanism. Results: We showed
      that NPMc+ increased the expression of PBX3 and HOXA9, which are both poor
      prognosis indicators in AML. High PBX3 and HOXA9 expression was accompanied by
      increased dimethylated and trimethylated H3K79 in transgenic murine Lin-Sca-1+c
      Kit+ cells and human NPMc+ leukemia cells. Using chromatin immunoprecipitation
      sequencing (ChIP-seq) assays of NPMc+ cells, we determined that hypermethylated
      H3K79 was present at the expressed HOXA9 gene but not the PBX3 gene. PBX3
      expression was positively regulated by HOXA9, and a reduction in either PBX3 or
      HOXA9 resulted in NPMc+ cell apoptosis. Importantly, an inhibitor of DOT1L,
      EPZ5676, effectively and selectively promoted NPMc+ human leukemic cell apoptosis
      by reducing HOXA9 and PBX3 expression. Conclusion: Our data indicate that NPMc+
      leukemic cell survival requires upregulation of PBX3 and HOXA9, and this action
      can be largely attenuated by a DOT1L inhibitor.

PMID- 30214627
TI  - 3D printing of Mo-containing scaffolds with activated anabolic responses and bi
      lineage bioactivities.
AB  - When osteochondral tissues suffer from focal or degenerative lesions caused by
      trauma or disorders, it is a tough challenge to regenerate them because of the
      limited self-healing capacity of articular cartilage. In this study, a series of
      Mo-doped bioactive glass ceramic (Mo-BGC) scaffolds were prepared and then
      systematically characterized. The released MoO42- ions from 7.5Mo-BGC scaffolds
      played a vital role in regenerating articular cartilage and subchondral bone
      synchronously. Methods: The Mo-BGC scaffolds were fabricated through employing
      both a sol-gel method and 3D printing technology. SEM, EDS, HRTEM, XRD, ICPAES
      and mechanical strength tests were respectively applied to analyze the
      physicochemical properties of Mo-BGC scaffolds. The proliferation and
      differentiation of rabbit chondrocytes (RCs) and human bone mesenchymal stem
      cells (HBMSCs) cultured with dilute solutions of 7.5Mo-BGC powder extract were
      investigated in vitro. The co-culture model was established to explore the
      possible mechanism of stimulatory effects of MoO42- ions on the RCs and HBMSCs.
      The efficacy of regenerating articular cartilage and subchondral bone using 7.5Mo
      BGC scaffolds was evaluated in vivo. Results: The incorporation of Mo into BGC
      scaffolds effectively enhanced the compressive strength of scaffolds owing to the
      improved surface densification. The MoO42- ions released from the 7.5Mo-BGC
      powders remarkably promoted the proliferation and differentiation of both RCs and
      HBMSCs. The MoO42- ions in the co-culture system significantly stimulated the
      chondrogenic differentiation of RCs and meanwhile induced the chondrogenesis of
      HBMSCs. The chondrogenesis stimulated by MoO42- ions happened through two
      pathways: 1) MoO42- ions elicited anabolic responses through activating the HIF
      1alpha signaling pathway; 2) MoO42- ions inhibited catabolic responses and
      protected cartilage matrix from degradation. The in vivo study showed that 7.5Mo
      BGC scaffolds were able to significantly promote cartilage/bone regeneration when
      implanted into rabbit osteochondral defects for 8 and 12 weeks, displaying bi
      lineage bioactivities. Conclusion: The 3D-printed Mo-BGC scaffolds with bi
      lineage bioactivities and activated anabolic responses could offer an effective
      strategy for cartilage/bone interface regeneration.

PMID- 30214628
TI  - State-of-the-art of microbubble-assisted blood-brain barrier disruption.
AB  - Focused ultrasound with microbubbles promises unprecedented advantages for blood
      brain barrier disruption over existing intracranial drug delivery methods, as
      well as a significant number of tunable parameters that affect its safety and
      efficacy. This review provides an engineering perspective on the state-of-the-art
      of the technology, considering the mechanism of action, effects of microbubble
      properties, ultrasound parameters and physiological variables, as well as safety
      and potential therapeutic applications. Emphasis is placed on the use of unified
      parameters, such as microbubble volume dose (MVD) and ultrasound mechanical
      index, to optimize the procedure and establish safety limits. It is concluded
      that, while efficacy has been demonstrated in several animal models with a wide
      range of payloads, acceptable measures of safety should be adopted to accelerate
      collaboration and improve understanding and clinical relevance.

PMID- 30214629
TI  - Suppression of metastasis through inhibition of chitinase 3-like 1 expression by
      miR-125a-3p-mediated up-regulation of USF1.
AB  - Rationale: Chitinase 3-like 1 (Chi3L1) protein is up-regulated in various
      diseases including solid cancers. According to Genome-Wide Association Study
      (GWAS)/Online Mendelian Inheritance in Man (OMIM)/Differentially Expressed Gene
      (DEG) analyses, Chi3L1 is associated with 38 cancers, and more highly associated
      with cancer compared to other oncogenes such as EGFR, TNFalpha, etc. However, the
      mechanisms and pathways by which Chi3L1 is associated with cancer are not clear.
      In current study, we investigated the role of Chi3L1 in lung metastasis. Methods:
      We performed the differentially expressed gene analysis to explore the genes
      which are associated with Chi3L1 using the web-based platform from Biomart. We
      investigated the metastases in lung tissues of C57BL/6 mice injected with B16F10
      melanoma following treatment with Ad-shChi3L1. We also investigated the
      expression of USF1 and Chi3L1 in Chi3L1 KD mice lung tissues by Western blotting
      and IHC. We also analyzed lung cancer cells metastases induced by Chi3L1 using
      migration and cell proliferation assay in human lung cancer cell lines. The
      involvement of miR-125a-3p in Chi3L1 regulation was determined by miRNA qPCR and
      luciferase reporter assay. Results: We showed that melanoma metastasis in lung
      tissues was significantly reduced in Chi3L1 knock-down mice, accompanied by down
      regulation of MMP-9, MMP-13, VEGF, and PCNA in Chi3L1 knock-down mice lung
      tissue, as well as in human lung cancer cell lines. We also found that USF1 was
      conversely expressed against Chi3L1. USF1 was increased by knock-down of Chi3L1
      in mice lung tissues, as well as in human lung cancer cell lines. In addition,
      knock-down of USF1 increased Chi3L1 levels in addition to augmenting metastasis
      cell migration and proliferation in mice model, as well as in human cancer cell
      lines. Moreover, in human lung tumor tissues, the expression of Chi3L1 was
      increased but USF1 was decreased in a stage-dependent manner. Finally, Chi3L1
      expression was strongly regulated by the indirect translational suppressing
      activity of USF1 through induction of miR-125a-3p, a target of Chi3L1.
      Conclusion: Metastases in mice lung tissues and human lung cancer cell lines were
      decreased by KD of Chi3L1. USF1 bound to the Chi3L1 promoter, however, Chi3L1
      expression was decreased by USF1, despite USF1 enhancing the transcriptional
      activity of Chi3L1. We found that USF1 induced miR-125a-3p levels which
      suppressed Chi3L1 expression. Ultimately, our results suggest that lung
      metastasis is suppressed by knock-down of Chi3L1 through miR-125a-3p-mediated up
      regulation of USF1.

PMID- 30214630
TI  - Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal
      cord injury repair.
AB  - Proper selection and effective delivery of combination drugs targeting multiple
      pathophysiological pathways key to spinal cord injury (SCI) hold promise to
      address the thus far scarce clinical therapeutics for improving recovery after
      SCI. In this study, we aim to develop a clinically feasible way for targeted
      delivery of multiple drugs with different physiochemical properties to the SCI
      site, detail the underlying mechanism of neural recovery, and detect any
      synergistic effect related to combination therapy. Methods: Liposomes (LIP)
      modified with a scar-targeted tetrapeptide (cysteine-alanine-glutamine-lysine,
      CAQK) were first constructed to simultaneously encapsulate docetaxel (DTX) and
      brain-derived neurotrophic factor (BDNF) and then were further added into a
      thermosensitive heparin-modified poloxamer hydrogel (HP) with affinity-bound
      acidic fibroblast growth factor (aFGF-HP) for local administration into the SCI
      site (CAQK-LIP-GFs/DTX@HP) in a rat model. In vivo fluorescence imaging was used
      to examine the specificity of CAQK-LIP-GFs/DTX binding to the injured site.
      Multiple comprehensive evaluations including biotin dextran amine anterograde
      tracing and magnetic resonance imaging were used to detect any synergistic
      effects and the underlying mechanisms of CAQK-LIP-GFs/DTX@HP both in vivo (rat
      SCI model) and in vitro (primary neuron). Results: The multiple drugs were
      effectively delivered to the injured site. The combined application of GFs and
      DTX supported neuro-regeneration by improving neuronal survival and plasticity,
      rendering a more permissive extracellular matrix environment with improved
      regeneration potential. In addition, our combination therapy promoted axonal
      regeneration via moderation of microtubule function and mitochondrial transport
      along the regenerating axon. Conclusion: This novel multifunctional therapeutic
      strategy with a scar-homing delivery system may offer promising translational
      prospects for the clinical treatment of SCI.

PMID- 30214631
TI  - Aspirin cooperates with p300 to activate the acetylation of H3K9 and promote FasL
      mediated apoptosis of cancer stem-like cells in colorectal cancer.
AB  - Cancer stem-like cells (CSCs) have been proposed as a key driving force of tumor
      growth and relapse in colorectal cancer (CRC), and therefore, they are promising
      targets for cancer therapy. Epidemiological evidence has suggested that the daily
      use of aspirin reduces overall mortality of CRC and the risk of distant
      metastasis. We investigated the effect and mechanism of aspirin on CSCs in CRC.
      Methods: The ratio of CSCs was analyzed after aspirin treatment both in a cell
      model and patient samples. Chemically modified aspirin and immunoprecipitation
      were adopted to detect the target proteins of aspirin. A locus-specific light
      inducible epigenetic modification system based on CRISPR technology was
      constructed to verify the causal relationship in these molecular events. In vivo
      characterization was performed in a xenograft model. Results: We found that
      aspirin induces apoptosis in enriched colorectal CSCs, inhibits tumor
      progression, and enhances the anti-neoplastic effects of chemotherapeutic agents.
      Furthermore, aspirin directly interacts with p300 in the nucleus, promotes H3K9
      acetylation, activates FasL expression, and induces apoptosis in colorectal CSCs.
      Notably, these effects of aspirin are absent in non-CSCs since H3K9 is
      hypermethylated in non-CSCs and the effects are not induced by other NSAIDs. In
      addition, aspirin can suppress oxaliplatin-enriched CSCs and serve as an adjuvant
      therapy. Conclusions: Taken together, we revealed a unique epigenetic and cox
      independent pathway (p300-AcH3K9-FasL axis) by which aspirin eliminates
      colorectal CSCs. These findings establish an innovative framework of the
      therapeutic significance of aspirin.

PMID- 30214632
TI  - Radionuclide imaging of VEGFR2 in glioma vasculature using biparatopic affibody
      conjugate: proof-of-principle in a murine model.
AB  - Vascular endothelial growth factor receptor-2 (VEGFR2) is a key mediator of
      angiogenesis and therefore a promising therapeutic target in malignancies
      including glioblastoma multiforme (GBM). Molecular imaging of VEGFR2 expression
      may enable patient stratification for antiangiogenic therapy. The goal of the
      current study was to evaluate the capacity of the novel anti-VEGFR2 biparatopic
      affibody conjugate (ZVEGFR2-Bp2) for in vivo visualization of VEGFR2 expression
      in GBM. Methods: ZVEGFR2-Bp2 coupled to a NODAGA chelator was generated and
      radiolabeled with indium-111. The VEGFR2-expressing murine endothelial cell line
      MS1 was used to evaluate in vitro binding specificity and affinity, cellular
      processing and targeting specificity in mice. Further tumor targeting was studied
      in vivo in GL261 glioblastoma orthotopic tumors. Experimental imaging was
      performed. Results: [111In]In-NODAGA-ZVEGFR2-Bp2 bound specifically to VEGFR2
      (KD=33+/-18 pM). VEGFR2-mediated accumulation was observed in liver, spleen and
      lungs. The tumor-to-organ ratios 2 h post injection for mice bearing MS1 tumors
      were approximately 11 for blood, 15 for muscles and 78 for brain. Intracranial
      GL261 glioblastoma was visualized using SPECT/CT. The activity uptake in tumors
      was significantly higher than in normal brain tissue. The tumor-to-cerebellum
      ratios after injection of 4 ug [111In]In-NODAGA-ZVEGFR2-Bp2 were significantly
      higher than the ratios observed for the 40 ug injected dose and for the non
      VEGFR2 binding size-matched conjugate, demonstrating target specificity.
      Microautoradiography of cryosectioned CNS tissue was in good agreement with the
      SPECT/CT images. Conclusion: The anti-VEGFR2 affibody conjugate [111In]In-NODAGA
      ZVEGFR2-Bp2 specifically targeted VEGFR2 in vivo and visualized its expression in
      a murine GBM orthotopic model. Tumor-to-blood ratios for [111In]In-NODAGA-ZVEGFR2
      Bp2 were higher compared to other VEGFR2 imaging probes. [111In]In-NODAGA-ZVEGFR2
      Bp2 appears to be a promising probe for in vivo noninvasive visualization of
      tumor angiogenesis in glioblastoma.

PMID- 30214633
TI  - Integration of magnetic resonance imaging and protein and metabolite CSF
      measurements to enable early diagnosis of secondary progressive multiple
      sclerosis.
AB  - Molecular networks in neurological diseases are complex. Despite this fact,
      contemporary biomarkers are in most cases interpreted in isolation, leading to a
      significant loss of information and power. We present an analytical approach to
      scrutinize and combine information from biomarkers originating from multiple
      sources with the aim of discovering a condensed set of biomarkers that in
      combination could distinguish the progressive degenerative phenotype of multiple
      sclerosis (SPMS) from the relapsing-remitting phenotype (RRMS). Methods: Clinical
      and magnetic resonance imaging (MRI) data were integrated with data from protein
      and metabolite measurements of cerebrospinal fluid, and a method was developed to
      sift through all the variables to establish a small set of highly informative
      measurements. This prospective study included 16 SPMS patients, 30 RRMS patients
      and 10 controls. Protein concentrations were quantitated with multiplexed
      fluorescent bead-based immunoassays and ELISA. The metabolome was recorded using
      liquid chromatography-mass spectrometry. Clinical follow-up data of the SPMS
      patients were used to assess disease progression and development of disability.
      Results: Eleven variables were in combination able to distinguish SPMS from RRMS
      patients with high confidence superior to any single measurement. The identified
      variables consisted of three MRI variables: the size of the spinal cord and the
      third ventricle and the total number of T1 hypointense lesions; six proteins:
      galectin-9, monocyte chemoattractant protein-1 (MCP-1), transforming growth
      factor alpha (TGF-alpha), tumor necrosis factor alpha (TNF-alpha), soluble CD40L
      (sCD40L) and platelet-derived growth factor AA (PDGF-AA); and two metabolites:
      20beta-dihydrocortisol (20beta-DHF) and indolepyruvate. The proteins myelin basic
      protein (MBP) and macrophage-derived chemokine (MDC), as well as the metabolites
      20beta-DHF and 5,6-dihydroxyprostaglandin F1a (5,6-DH-PGF1), were identified as
      potential biomarkers of disability progression. Conclusion: Our study
      demonstrates, in a limited but well-defined and data-rich cohort, the importance
      and value of combining multiple biomarkers to aid diagnostics and track disease
      progression.

PMID- 30214634
TI  - Therapeutic mesopore construction on 2D Nb2C MXenes for targeted and enhanced
      chemo-photothermal cancer therapy in NIR-II biowindow.
AB  - Two-dimensional (2D) MXenes have emerged as a promising planar theranostic
      nanoplatform for versatile biomedical applications; but their in vivo behavior
      and performance has been severely influenced and hindered by a lack of necessary
      surface chemistry for adequate surface engineering. To solve this critical issue,
      this work employs versatile sol-gel chemistry for the construction of a unique
      "therapeutic mesopore" layer onto the surface of 2D niobium carbide (Nb2C) MXene.
      Methods: The in situ self-assembled mesopore-making agent
      (cetanecyltrimethylammonium chloride, in this case) was kept within the mesopores
      for efficient chemotherapy. The abundant surface saline chemistry of mesoporous
      silica-coated Nb2C MXene was further adopted for stepwise surface engineering
      including PEGylation and conjugation with cyclic arginine-glycine-aspartic
      pentapeptide c(RGDyC) for targeted tumor accumulation. Results: 2D Nb2C MXenes
      were chosen based on their photothermal conversion capability (28.6%) in the near
      infrared (NIR)-II biowindow (1064 nm) for enhanced photothermal hyperthermia.
      Systematic in vitro and in vivo assessments demonstrate targeted and enhanced
      chemotherapy and photothermal hyperthermia of cancer (U87 cancer cell line and
      corresponding tumor xenograft; inhibition efficiency: 92.37%) in the NIR-II
      biowindow by these mesopore-coated 2D Nb2C MXenes. Conclusion: This work not only
      significantly broadens the biomedical applications of 2D Nb2C MXene for enhanced
      cancer therapy, but also provides an efficient strategy for surface engineering
      of 2D MXenes to satisfy versatile application requirements.

PMID- 30214635
TI  - CD28null pro-atherogenic CD4 T-cells explain the link between CMV infection and
      an increased risk of cardiovascular death.
AB  - An increased risk of cardiovascular death in Cytomegalovirus (CMV)-infected
      individuals remains unexplained, although it might partly result from the fact
      that CMV infection is closely associated with the accumulation of CD28null T
      cells, in particular CD28null CD4 T-cells. These cells can directly damage
      endothelium and precipitate cardiovascular events. However, the current paradigm
      holds that the accumulation of CD28null T-cells is a normal consequence of aging,
      whereas the link between these T-cell populations and CMV infection is explained
      by the increased prevalence of this infection in older people. Resolving whether
      CMV infection or aging triggers CD28null T-cell expansions is of critical
      importance because, unlike aging, CMV infection can be treated. Methods: We used
      multi-color flow-cytometry, antigen-specific activation assays, and HLA-typing to
      dissect the contributions of CMV infection and aging to the accumulation of
      CD28null CD4 and CD8 T-cells in CMV+ and CMV- individuals aged 19 to 94 years.
      Linear/logistic regression was used to test the effect of sex, age, CMV
      infection, and HLA-type on CD28null T-cell frequencies. Results: The median
      frequencies of CD28null CD4 T-cells and CD28null CD8 T-cells were >12-fold
      (p=0.000) but only approximately 2-fold higher (p=0.000), respectively, in CMV+
      (n=136) compared with CMV- individuals (n=106). The effect of CMV infection on
      these T-cell subsets was confirmed by linear regression. Unexpectedly, aging
      contributed only marginally to an increase in CD28null T-cell frequencies, and
      only in CMV+ individuals. Interestingly, the presence of HLA-DRB1*0301 led to an
      approximately 9-fold reduction of the risk of having CD28null CD4 T-cell
      expansions (OR=0.108, p=0.003). Over 75% of CMV-reactive CD4 T-cells were
      CD28null. Conclusion: CMV infection and HLA type are major risk factors for
      CD28null CD4 T-cell-associated cardiovascular pathology. Increased numbers of
      CD28null CD8 T-cells are also associated with CMV infection, but to a lesser
      extent. Aging, however, makes only a negligible contribution to the expansion of
      these T-cell subsets, and only in the presence of CMV infection. Our results open
      up new avenues for risk assessment, prevention, and treatment.

PMID- 30214636
TI  - Rewiring of cisplatin-resistant bladder cancer cells through epigenetic
      regulation of genes involved in amino acid metabolism.
AB  - Alterations in DNA methylation are important epigenetic markers in bladder cancer
      (BC). These epigenome modifications may drive the mechanisms of aggressive chemo
      resistant BC. Clinicopathological biomarkers that indicate chemotherapeutic
      resistance are critical for better assessing treatment strategies for individual
      patients. Thus, in this study, we aimed to determine whether DNA methylation of
      certain metabolic enzymes is significantly altered in cisplatin-resistant BC
      cells. Methods: To characterize CpG methylation and nucleosome accessibility in
      cisplatin-resistant BC cells, the Illumina Infinium HM450 DNA methylation assay
      was performed. Perturbed gene expression was found to be associated with
      cisplatin resistance, and the biological roles of spermidine/spermine N1
      acetyltransferase (SAT1) and argininosuccinate synthase 1 (ASS1) were further
      studied using qRT-PCR analysis and various cell biology assays, including western
      blot. Results:ASS1 and SAT1, genes for amino acid and polyamine metabolism
      catalysts, respectively, were found to be vastly hypermethylated, resulting in
      greatly downregulated expression. ASS1 expression is of particular interest
      because prior studies have demonstrated its potential association with BC stage
      and recurrence. In regard to chemoresistance, we found that aberrant expression
      or induced stimulation of SAT1 restored cisplatin sensitivity in the cell culture
      system. We also found that the addition of exogenous arginine deiminase through
      administration of ADI-PEG 20 (pegylated arginine deiminase) increased ASS1
      expression and enhanced cisplatin's apoptotic effects. Conclusions: Our study
      demonstrates a novel mechanistic link between the epigenetic perturbation of SAT1
      and ASS1 and cancer metabolism in cisplatin-resistant bladder cancer cells. These
      findings suggest potential utility of SAT1 and ASS1 as predictive biomarkers in
      re-sensitizing bladder cancer to chemotherapy and personalizing therapy.

PMID- 30214638
TI  - Liver-heart crosstalk controls IL-22 activity in cardiac protection after
      myocardial infarction.
AB  - Interleukin (IL)-22 regulates tissue inflammation and repair. Here we report
      participation of the liver in IL-22-mediated cardiac repair after acute
      myocardial infarction (MI). Methods: We induced experimental MI in mice by
      ligation of the left ascending artery and evaluated the effect of IL-22 on post
      MI cardiac function and ventricular remodeling. Results: Daily subcutaneous
      injection of 100 ug/kg mouse recombinant IL-22 for seven days attenuated adverse
      ventricular remodeling and improved cardiac function in mice at 28 days after
      left anterior descending coronary artery ligation-induced MI. Pharmacological
      inhibition of signal transducer and activator of transcription (STAT3) muted
      these IL-22 activities. While cardiomyocyte-selective depletion of STAT3 did not
      affect IL-22 activities in protecting post-MI cardiac injury, hepatocyte-specific
      depletion of STAT3 fully muted these IL-22 cardioprotective activities.
      Hepatocyte-derived fibroblast growth factor (FGF21) was markedly increased in a
      STAT3-dependent manner following IL-22 administration and accounted for the
      cardioprotective benefit of IL-22. Microarray analyses revealed that FGF21
      controlled the expression of cardiomyocyte genes that are involved in cholesterol
      homeostasis, DNA repair, peroxisome, oxidative phosphorylation, glycolysis,
      apoptosis, and steroid responses, all of which are responsible for cardiomyocyte
      survival. Conclusions: Supplementation of IL-22 in the first week after acute MI
      effectively prevented left ventricular dysfunction and heart failure. This
      activity of IL-22 involved crosstalk between the liver and heart after
      demonstrating a role of the hepatic STAT3-FGF21 axis in IL-22-induced post-MI
      cardiac protection.

PMID- 30214637
TI  - AMPK: Potential Therapeutic Target for Ischemic Stroke.
AB  - 5'-AMP-activated protein kinase (AMPK), a member of the serine/threonine
      (Ser/Thr) kinase group, is universally distributed in various cells and organs.
      It is a significant endogenous defensive molecule that responds to harmful
      stimuli, such as cerebral ischemia, cerebral hemorrhage, and, neurodegenerative
      diseases (NDD). Cerebral ischemia, which results from insufficient blood flow or
      the blockage of blood vessels, is a major cause of ischemic stroke. Ischemic
      stroke has received increased attention due to its '3H' effects, namely high
      mortality, high morbidity, and high disability. Numerous studies have revealed
      that activation of AMPK plays a protective role in the brain, whereas its action
      in ischemic stroke remains elusive and poorly understood. Based on existing
      evidence, we introduce the basic structure, upstream regulators, and biological
      roles of AMPK. Second, we analyze the relationship between AMPK and the
      neurovascular unit (NVU). Third, the actions of AMPK in different phases of
      ischemia and current therapeutic methods are discussed. Finally, we evaluate
      existing controversy and provide a detailed analysis, followed by ethical issues,
      potential directions, and further prospects of AMPK. The information complied
      here may aid in clinical and basic research of AMPK, which may be a potent drug
      candidate for ischemic stroke treatment in the future.

PMID- 30214639
TI  - [18F]Fludarabine-PET as a promising tool for differentiating CNS lymphoma and
      glioblastoma: Comparative analysis with [18F]FDG in human xenograft models.
AB  - This paper investigated whether positron emission tomography (PET) imaging with
      [18F]fludarabine ([18F]FDB) can help to differentiate central nervous system
      lymphoma (CNSL) from glioblastoma (GBM), which is a crucial issue in the
      diagnosis and management of patients with these aggressive brain tumors.
      Multimodal analyses with [18F]fluorodeoxyglucose ([18F]FDG), magnetic resonance
      imaging (MRI) and histology have also been considered to address the specificity
      of [18F]FDB for CNSL. Methods: Nude rats were implanted with human MC116 lymphoma
      cells (n = 9) or U87 glioma-cells (n = 4). Tumor growth was monitored by MRI,
      with T2-weighted sequence for anatomical features and T1-weighted with gadolinium
      (Gd) enhancement for blood brain barrier (BBB) permeability assessment. For PET
      investigation, [18F]FDB or [18F]FDG (~11 MBq) were injected via tail vein and
      dynamic PET images were acquired up to 90 min after radiotracer injection. Paired
      scans of the same rat with the two [18F]-labelled radiotracers were investigated.
      Initial volumes of interest were manually delineated on T2w images and set on co
      registered PET images and tumor-to-background ratio (TBR) was calculated to semi
      quantitatively assess the tracer accumulation in the tumor. A tile-based method
      for image analysis was developed in order to make comparative analysis between
      radiotracer uptake and values extracted from immunohistochemistry staining.
      Results: In the lymphoma model, PET time-activity curves (TACs) revealed a
      differential response of [18F]FDB between tumoral and healthy tissues with
      average TBR varying from 2.45 to 3.16 between 5 to 90 min post-injection. In
      contrast, [18F]FDG demonstrated similar uptake profiles for tumoral and normal
      regions with TBR varying from 0.84 to 1.06 between these two time points. In the
      glioblastoma (GBM) model, the average TBRs were from 2.14 to 1.01 for [18F]FDB
      and from 0.95 to 1.65 for [18F]FDG. Therefore, inter-model comparisons showed
      significantly divergent responses (p < 0.01) of [18F]FDB between lymphoma and
      GBM, while [18F]FDG demonstrated overlap (p = 0.04) between the groups. Tumor
      characterization with histology (based mainly on Hoechst and CD79), as well as
      with MRI was overall in better agreement with [18F]FDB-PET than [18F]FDG with
      regard to tumor selectivity. Conclusions: [18F]FDB-PET demonstrated considerably
      greater specificity for CNSL when compared to [18F]FDG. It also permitted a more
      precise definition of target volume compared to contrast-enhanced MRI. Therefore,
      the potential of [18F]FDB-PET to distinguish CNSL from GBM is quite evident and
      will be further investigated in humans.

PMID- 30214641
TI  - Integrated identification and quantification of cyanobacterial toxins from
      Pacific Northwest freshwaters by Liquid Chromatography and High-resolution Mass
      Spectrometry.
AB  - The occurrence of harmful algal blooms in nutrient-rich freshwater bodies has
      increased world-wide, including in the Pacific Northwest. Some cyanobacterial
      genera have the potential to produce secondary metabolites that are highly toxic
      to humans, livestock and wildlife. Reliable methods for the detection of
      cyanobacterial toxins with high specificity and low limits of detection are in
      high demand. Here we test a relatively new hybrid high resolution accurate mass
      quadrupole time-of-flight mass spectrometry platform (TripleTOF) for the analysis
      of cyanobacterial toxins in freshwater samples. We developed a new method that
      allows the quantitative analysis of four commonly observed microcystin congeners
      (LR, LA, YR, and RR) and anatoxin-a in a 6-min LC run without solid-phase
      enrichment. Limits of detection for the microcystin congeners (LR, LA, YR, and
      RR) and anatoxin-a were <5 ng/L (200-fold lower than the guideline value of 1
      MUg/L as maximum allowable concentration of MC-LR in drinking water). The method
      was applied for screening freshwaters in the Pacific Northwest during the bloom
      and post-bloom periods. The use of high resolution mass spectrometry and
      concomitant high sensitivity detection of specific fragment ions with high mass
      accuracy provides an integrated approach for the simultaneous identification and
      quantification of cyanobacterial toxins. The method is sensitive enough for
      detecting the toxins in single Microcystis colonies.

PMID- 30214640
TI  - Biomarkers of legume intake in human intervention and observational studies: a
      systematic review.
AB  - There is a growing interest in assessing dietary intake more accurately across
      different population groups, and biomarkers have emerged as a complementary tool
      to replace traditional dietary assessment methods. The purpose of this study was
      to conduct a systematic review of the literature available and evaluate the
      applicability and validity of biomarkers of legume intake reported across various
      observational and intervention studies. A systematic search in PubMed, Scopus,
      and ISI Web of Knowledge identified 44 studies which met the inclusion criteria
      for the review. Results from observational studies focused on soy or soy-based
      foods and demonstrated positive correlations between soy intake and urinary,
      plasma or serum isoflavonoid levels in different population groups. Similarly,
      intervention studies demonstrated increased genistein and daidzein levels in
      urine and plasma following soy intake. Both genistein and daidzein exhibited dose
      response relationships. Other isoflavonoid levels such as O-desmethylangolensin
      (O-DMA) and equol were also reported to increase following soy consumption. Using
      a developed scoring system, genistein and daidzein can be considered as promising
      candidate markers for soy consumption. Furthermore, genistein and daidzein also
      served as good estimates of soy intake as evidenced from long-term exposure
      studies marking their status as validated biomarkers. On the contrary, only few
      studies indicated proposed biomarkers for pulses intake, with pipecolic acid and
      S-methylcysteine reported as markers reflecting dry bean consumption, unsaturated
      aliphatic, hydroxyl-dicarboxylic acid related to green beans intake and
      trigonelline reported as marker of peas consumption. However, data regarding
      criteria such as specificity, dose-response and time-response relationship,
      reliability, and feasibility to evaluate the validity of these markers is
      lacking. In conclusion, despite many studies suggesting proposed biomarkers for
      soy, there is a lack of information on markers of other different subtypes of
      legumes. Further discovery and validation studies are needed in order to identify
      reliable biomarkers of legume intake.

PMID- 30214643
TI  - Polyglobulia in patients with hemangioblastomas is related to tumor size but not
      to serum erythropoietin.
AB  - Background: Hemangioblastomas are associated with elevated hemoglobin (Hb) levels
      (polyglobulia), which is associated with a higher risk for cerebral stroke,
      cardiac infarction and pulmonary embolism. The pathomechanism of polyglobulia
      remains unclear and different theories have been postulated. Among those are
      elevated serum erythropoietin (EPO) levels caused by secretion of the tumor or
      associated tumor cyst. Methods: To elucidate the pathomechanism, we
      systematically investigated the relation between polyglobulia, serum EPO level,
      size of the solid tumor and associated cyst in hemangioblastomas. We
      prospectively evaluated hemoglobin and EPO levels in a series of 33 consecutive
      patients operated on hemangioblastomas in our center. We measured the size of the
      solid tumor and associated cyst in magnetic resonance imaging. Statistical
      evaluations were performed using the Fisher's exact test and student's t-test.
      Results: As a result five patients had elevated hemoglobin levels. Only one of
      these had an elevated serum EPO level. Of 26 patients with normal hemoglobin
      levels, 4 patients had elevated EPO levels.Patients with low or normal hemoglobin
      levels (84%) had an average tumor size of 0.8 cm3, which differed significantly
      from patients with elevated hemoglobin levels (16%), who had an average solid
      tumor size of 8.0 cm3 (p < 0.05). We did not observe a significant correlation
      between EPO levels or polyglobulia and associated cysts. Conclusions: We
      therefore conclude that in contrast to previous case reports and interpretations,
      our data show no correlation between polyglobulia and EPO levels or associated
      cysts in patients with hemangioblastomas. In fact, it is the size of the solid
      tumor that correlates with polyglobulia.The study was retrospectively registered
      in the German Clinical Trial Registry on 10 July 2014; Trial registration:
      DRKS00006310.

PMID- 30214642
TI  - Morphology regulation in vascular endothelial cells.
AB  - Morphological change in endothelial cells is an initial and crucial step in the
      process of establishing a functional vascular network. Following or associated
      with differentiation and proliferation, endothelial cells elongate and assemble
      into linear cord-like vessels, subsequently forming a perfusable vascular tube.
      In vivo and in vitro studies have begun to outline the underlying genetic and
      signaling mechanisms behind endothelial cell morphology regulation. This review
      focuses on the transcription factors and signaling pathways regulating
      endothelial cell behavior, involved in morphology, during vascular development.

PMID- 30214644
TI  - Type 2 Diabetes and Glycemic Variability: Various Parameters in Clinical
      Practice.
AB  - It has become possible to measure blood glucose levels continuously from 24 h to
      approximately 2 weeks due to the recent development of relevant devices such as
      continuous glucose monitoring and flash glucose monitoring systems. This has
      enabled not only medical professionals but also patients to monitor details of
      glycemic variability (GV) which was not possible in the past. Details of GV for
      both short and intermediate periods can now be obtained, and it is important in
      patient care to appropriately evaluate the data obtained. Types of GV in terms of
      time frame vary from short-term to long-term. Several studies reported that long
      term GV was related to micro- and macro-angiopathies in patients with type 2
      diabetes mellitus (T2DM). However, there are still unknown aspects regarding the
      relationships of various durations of GV with prognosis. Further clinical trials
      are required to examine the mechanism of GV and to evaluate whether GV can be a
      valuable therapeutic target in treatment of patients with T2DM.

PMID- 30214645
TI  - Pancreatic Involvement in Inflammatory Bowel Disease: A Review.
AB  - Inflammatory bowel disease (IBD) is a multisystemic disease, and pancreatic
      manifestations of IBD are not uncommon. The incidence of several pancreatic
      diseases in Crohn's disease and ulcerative colitis is more frequent compared to
      the general population. Pancreatic manifestations in IBD include a wide
      heterogenic group of disorders and abnormalities of the pancreas and range from
      mild self-limited diseases to severe disorders. Acute pancreatitis, chronic
      pancreatitis, autoimmune pancreatitis, pancreatic autoantibodies, exocrine
      pancreatic insufficiency and asymptomatic imaging and laboratory abnormalities
      are included in related-IBD pancreatic manifestations. Involvement of the
      pancreas in IBD may be the result of IBD itself or of medications used.

PMID- 30214646
TI  - Dysfunction and Therapeutic Potential of Endothelial Progenitor Cells in Diabetes
      Mellitus.
AB  - Diabetes mellitus (DM) is a chronic, multifactorial metabolic disease whereby
      insulin deficiency or resistance results in hyperglycemia. Endothelial cells
      (ECs) form the innermost layer of the blood vessel and produce and release a
      variety of vasoactive substances and growth factors to regulate vascular
      homeostasis and angiogenesis. Hyperglycemia and insulin resistance can cause
      endothelial dysfunction, leading to vascular complications such as coronary
      artery disease, peripheral arterial disease, diabetic nephropathy, neuropathy and
      retinopathy. The detrimental effect exerted on ECs by hyperglycemia and insulin
      resistance underlines the importance of reparatory mechanisms in DM. Endothelial
      progenitor cells (EPCs), derived from bone marrow, have been recognized as
      endogenous cells involved in endothelial repair and new blood vessel formation.
      Initially isolated from a subset of circulating CD34+ mononuclear cells, EPCs
      were found to possess the ability to differentiate into ECs when cultured in
      vitro and incorporate into newly formed vessels upon transplantation in animal
      models of ischemia. Due to the low frequency of CD34+ cells in circulation, the
      vast majority of studies investigating EPC actions have used cells that are
      generated through the culture of peripheral blood mononuclear cells (PBMNCs) for
      4 - 7 days in endothelial selective medium. These cells, mainly of myeloid
      hematopoietic cell origin, were termed "Early EPCs," of which, few expressed
      stem/progenitor-cell markers. Therefore, early EPCs were also termed "myeloid
      angiogenic cells" (MACs). When PBMNCs are cultured for over 2 weeks, early EPCs
      gradually diminish while so-called late EPCs appear. Late EPCs share phenotypic
      features with mature ECs and are therefore also termed blood-derived ECs; they
      will not be addressed in this review. MAC dysfunction has been observed in a
      variety of disease conditions including DM. In this article we review the
      activities and therapeutic potential of MACs in DM. We will interchangeably use
      "EPCs" and "MACs" to refer to the cells procured by culture of PBMNCs in EC
      selective medium for approximately 7 days.

PMID- 30214647
TI  - Practice Patterns of Inferior Vena Cava Filter Placement and Factors That Predict
      Retrieval Rates: A Single-Center Institution and Review of the Literature.
AB  - Background: There is a wide variability in practice patterns on the use of
      inferior vena cava filters (IVCFs) among institutions, which is likely due to
      contrasting indication guidelines published by different professional societies.
      The aim of the present study is to report our healthcare system use of IVCF to:
      1) determine practice patterns, 2) determine factors that may predict IVCF
      retrieval and 3) identify areas for improvement. Methods: A retrospective review
      of 180 consecutive IVCF placement performed between July 2014 and December 2015
      was conducted. Results: One hundred nine (60.6%) IVCFs were placed for absolute
      indications, 27 (15.0%) for relative indications, 26 (14.4%) prophylactically and
      18 (10.0%) for unknown indications. Average age was 59.3 years. Ninety-five had
      active cancer. Surgical and medical services requested filter placement in 112
      (62.2%) and 68 (37.8%) patients, respectively. Thirteen (7.2%) patients had a
      hematology consult prior to IVCF placement. Documentation of the presence of an
      IVCF was present in 118/127 (92.9%) discharge summaries, and outlined
      instructions for filter retrieval post-discharge were present in 20/124 (16.1%)
      cases. Only 33 (25.0%) IVCF were retrieved at a median interval of 162 days
      (range: 4 - 1,053 days). None of the factors of interest was found to be
      significantly associated with IVCF retrieval. Conclusion: A root cause analysis
      identified that the lack of a structured system for IVCF tracking resulted in
      poor IVCF retrieval rates. This study resulted in the development of a hospital
      initiated multidisciplinary team to address these issues.

PMID- 30214648
TI  - Number of Nodules but not Size of Hepatocellular Carcinoma Can Predict
      Refractoriness to Transarterial Chemoembolization and Poor Prognosis.
AB  - Background: To determine whether response to transarterial chemoembolization
      (TACE) predicts survival and to identify pretreatment factors associated with
      TACE response and prognosis. Methods: Between April and September 2010, 50
      patients underwent TACE for hepatocellular carcinoma. Response to TACE was
      assessed using post-treatment computed tomography (CT) and magnetic resonance
      imaging (MRI) scans and tumor marker levels and classified as Response Poor (P)
      and Non-poor (NP). Time zero was set to September 30, 2010, and survival rates
      were analyzed by landmarking. Cumulative survival rates were calculated using the
      Kaplan-Meier method and compared according to grades using the log-rank test;
      contributing factors to survival were analyzed using a Cox proportional hazards
      model. Pretreatment factors were analyzed for 109 TACE sessions performed until
      October 2017, using a multiple logistic regression model. Receiver operating
      characteristic (ROC) curves were generated to determine the best tumor number for
      predicting response P. Results: Response P patients showed significantly lower
      cumulative survival rates than Response NP patients (P < 0.001). On multivariate
      analysis, tumor number (hazard ratio (HR), 1.475), protein-induced vitamin-K
      absence-II (HR, 4.539), and the number of previous TACE sessions (HR, 1.472) were
      identified as pretreatment factors contributing to Response P. Further, pre
      treatment platelet count (HR, 0.876) and tumor number (HR, 1.330) were factors
      contributing to survival in multivariate analysis. ROC curve analysis revealed
      that the optimal cut-off value to discriminate Response P was 7.5. Conclusions:
      Response to TACE can predict survival. Pretreatment tumor number is a useful
      factor for predicting both TACE response and prognosis.

PMID- 30214649
TI  - Recommendations of Lifestyle Modification According to a Survey of First-Year
      University Students.
AB  - Background: We analyzed what kind of lifestyle modification first-year university
      students need based on the results of a health-consciousness survey conducted in
      first-year students immediately after they entered a university. Methods: This
      population-based cross-sectional study used a "questionnaire survey on lifestyle
      and health for promoting health" conducted in Japan in 2015. From among an
      initial pool of 3,912 students, we excluded 314 due to insufficient data. The
      remaining 3,598 students (2,206 males and 1,392 females) were divided into four
      groups according to body mass index (BMI) based on Japan Society for the Study of
      Obesity "Guidelines for the management of obesity disease 2016": low (18.5 >
      BMI), less than standard (22.0 > BMI >= 18.5), standard or higher (25.0 > BMI >=
      22.0) and obesity (BMI >= 25.0). Results: Females had an ideal body image that
      was at a lower body weight regardless of their BMI. Males in the low BMI and
      obesity groups tended to be less aware of health issues. For each level of BMI,
      and in both males and females, the most frequent report of stress was "sometimes
      feel". The most frequent method for relieving stress was spending time with
      friends. Among males, those in the obesity group spent more time with "personal
      computers, televisions and games, etc." in a sitting position. When students were
      asked to rank which of their lifestyle habits needed the most improvement, "lack
      of exercise" was the highest, followed by "irregular schedule" and "dietary
      habits". In daily living behavior, a significant difference was observed for
      "exercise" among males, but not females. Conclusion: The attitudes of both males
      and females regarding the importance of physical activity and the necessity of
      efforts to improve health are presented. Health education for university students
      based on the attitudes may be useful for the prevention of lifestyle-related
      diseases for themselves in the future and before they become parents.

PMID- 30214650
TI  - Pulmonary Artery Pseudoaneurysms in the Setting of Gout Polyarthropathy: A Case
      Report.
AB  - Pulmonary artery pseudoaneurysm is a dangerous pathology often missed as a
      differential and on imaging. With a 50% mortality rate early detection and
      intervention are critical to patient outcome, rendering diagnosis based on
      clinical grounds to be of paramount importance. A high index of suspicion should
      be placed on patients presenting with unprovoked hemoptysis, hemorrhage or
      hemothorax. Knowledge of the common causes of pulmonary artery pseudoaneurysms is
      also important; however, it is integral to note spontaneous occurrences in
      patients with no known risk factors. Herein, we report a case of an unprovoked
      pulmonary artery pseudoaneurysm in a 72-year-old male with no known risk factors
      or causes for the pathology. Additionally, we review the pathophysiology behind
      the potential association of polyarthritic gout as a cause of pulmonary artery
      pseudoaneurysms. To the best of our knowledge this is the first reported link
      between the two diseases, providing grounds to widen literature and increase
      diagnoses of pulmonary artery pseudoaneurysms.

PMID- 30214651
TI  - Methimazole-Induced Pauci-Immune Glomerulonephritis and Anti-Phospholipid
      Syndrome: An Important Association to Be Aware of.
AB  - While methimazole (MMI) is the first line treatment for hyperthyroidism, this
      medication is not devoid of adverse effects. In this article, we present a 70
      year-old male who admitted the hospital with right lower extremity pain and rash.
      The patient was recently treated with MMI for hyperthyroidism. Imaging studies
      revealed bilateral renal and splenic infarcts along with thrombosis of popliteal
      artery. Laboratory data revealed hematuria and proteinuria with positive (MPO),
      anti-proteinase-3 (PR3) and anti-cardiolipin IgG antibodies. Renal biopsy
      revealed pauci-immune glomerulonephritis and features with anti-phospholipid
      antibody syndrome (APS). MMI was discontinued and the patient was treated
      successfully with steroid therapy and anti-coagulation with resolution of
      proteinuria, hematuria and normalization of laboratory parameters. While MMI
      induced pauci-immune glomerulonephritis has been previously reported, its
      association with APS has never been described before. Our case demonstrates that
      this rare diagnosis can be treated by early withdrawal of MMI and initiation of
      steroids along with anticoagulation.

PMID- 30214653
TI  - A Different Effect of an Orexin Receptor Antagonist on Metabolic Parameters
      Between Diabetic Patients and Non-Diabetic Patients.

PMID- 30214652
TI  - Dabigatran-Induced Acute Interstitial Nephritis: An Important Complication of
      Newer Oral Anticoagulation Agents.
AB  - Acute kidney injury (AKI) due to an acute interstitial nephritis (AIN) is common
      and can lead to increased morbidity and mortality. Medications such as
      antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump
      inhibitors (PPI) and rifampin are common offending agents. Anticoagulant
      associated AIN is more frequently reported with the use of warfarin; however,
      only few case reports have reported an association with the use of novel oral
      anticoagulants (NOACs). Herein, we report the case of a 59-year-old male who
      developed AKI after initiating dabigatran for the treatment of atrial
      fibrillation. Laboratory data demonstrated elevated blood urea nitrogen (BUN) of
      115 mg/dL (baseline = 35 mg/dL) and serum creatinine (Cr) of 5.06 mg/dL (baseline
      = 1.3 mg/dL). Urinalysis revealed eosinophiluria. Renal biopsy disclosed diffuse
      tubulointerstitial nephritis and eosinophils and confirmed the diagnosis of AIN.
      At 1 week, renal function improved (BUN/Cr = 53/2.73 mg/dL) with steroid therapy
      and discontinuation of dabigatran. With an increasing use of NOACs, it is
      important to monitor renal function to diagnose AIN in a timely fashion. Early
      diagnosis and prompt treatment can mitigate serious renal damage induced by
      dabigatran.

PMID- 30214654
TI  - Strong Association Between Weight Reduction and Suppression of Cardiovascular
      Events in Recent Clinical Trials of DPP4 Inhibitors, GLP-1 Receptor Agonists, and
      SGLT2 Inhibitors.

PMID- 30214655
TI  - ADAPTIVE-WEIGHT BURDEN TEST FOR ASSOCIATIONS BETWEEN QUANTITATIVE TRAITS AND
      GENOTYPE DATA WITH COMPLEX CORRELATIONS.
AB  - High-throughput sequencing has often been used to screen samples from pedigrees
      or with population structure, producing genotype data with complex correlations
      rendered from both familial relation and linkage disequilibrium. With such data,
      it is critical to account for these genotypic correlations when assessing the
      contribution of variants by gene or pathway. Recognizing the limitations of
      existing association testing methods, we propose Adaptive-weight Burden Test
      (ABT), a retrospective, mixed-model test for genetic association of quantitative
      traits on genotype data with complex correlations. This method makes full use of
      genotypic correlations across both samples and variants, and adopts "data-driven"
      weights to improve power. We derive the ABT statistic and its explicit
      distribution under the null hypothesis, and demonstrate through simulation
      studies that it is generally more powerful than the fixed-weight burden test and
      family-based SKAT in various scenarios, controlling for the type I error rate.
      Further investigation reveals the connection of ABT with kernel tests, as well as
      the adaptability of its weights to the direction of genetic effects. The
      application of ABT is illustrated by a whole genome analysis of genes with common
      and rare variants associated with fasting glucose from the NHLBI "Grand
      Opportunity" Exome Sequencing Project.

PMID- 30214656
TI  - Oligomerization Alters Binding Affinity Between Amyloid Beta and a Modulator of
      Peptide Aggregation.
AB  - The soluble oligomeric form of the amyloid beta (Abeta) peptide is the major
      causative agent in the molecular pathogenesis of Alzheimer's disease (AD). We
      have previously developed a pyrroline-nitroxyl fluorene compound (SLF) that
      blocks the toxicity of Abeta. Here we introduce the multi-parametric surface
      plasmon resonance (MP-SPR) approach to quantify SLF binding and effect on the
      self-association of the peptide via a label-free, real-time approach. Kinetic
      analysis of SLF binding to Abeta and measurements of layer thickness alterations
      inform on the mechanism underlying the ability of SLF to inhibit Abeta toxicity
      and its progression towards larger oligomeric assemblies. Depending on the
      oligomeric state of Abeta, distinct binding affinities for SLF are revealed. The
      Abeta monomer and dimer uniquely possess sub-nanomolar affinity for SLF via a non
      specific mode of binding. SLF binding is weaker in oligomeric Abeta, which
      displays an affinity for SLF on the order of 100 MUM. To complement these
      experiments we carried out molecular docking and molecular dynamics simulations
      to explore how SLF interacts with the Abeta peptide. The MP-SPR results together
      with in silico modeling provide affinity data for the SLF-Abeta interaction and
      allow us to develop a new general method for examining protein aggregation.

PMID- 30214657
TI  - Barriers for nurses' participation in and utilisation of clinical research in
      three hospitals within the Kumasi Metropolis, Ghana.
AB  - Introduction: Scientific research results are a necessary base for high quality
      nursing practice. The level of implementation of research in the clinical
      setting, including nurses' participation in and knowledge of research results,
      have gained considerable attention internationally. However, the remarkable
      international increase of such studies does not apply to the Ghanaian context. We
      therefore set out to evaluate the degree of involvement of nurses in research, as
      well as their utilization patterns of research findings in Ghana. Objectives: the
      study sought to investigate the proportion of nurses involved in clinical
      research as well as barriers for nurses' participation and utilization of
      research findings, within the Kumasi Metropolis area, Ghana. Methods: A
      descriptive and analytical cross-sectional study design was used in this study. A
      47 item questionnaire elicited data on 158 participants' demographics, the
      proportion and the barriers to participation, which was then analyzed using SSPS
      version 17 software. Qualitative interviews with key informants complemented
      quantitative survey data. In-depth interviews with nurse managers at the
      hospitals in focus was conducted and analyzed thematically. Results: The study
      shows that 36.1% of the nurses, included in the study, had participated in
      research and only 25.3% of these had (knowingly) used specific research results
      in clinical practice. However, the level of research participation differed
      greatly between nurses working at different hospitals. Nurses' participation in
      clinical research was shown to be associated with their perception of benefit of
      research to practice as well as their understanding of time as a factor for them
      engaging in reading scientific articles. In addition, barriers associated with
      nurses' integration of research findings into the daily practice was their
      perceived lack of support from the collegium and their perception of research as
      not part of the nursing role. Conclusion: Findings from the study suggest that
      there is a need to create institutional support to facilitate and encourage
      nurses' participation in research, yet also to formalize nurses' continuous
      professional development. This, could change nurses' attitudes towards research,
      and contribute to improving health care as it would increase nurses' role as
      agents for evidence based clinical practice.

PMID- 30214658
TI  - Anaphylaxis triggers in a large tertiary care hospital in Qatar: a retrospective
      study.
AB  - Background: Anaphylaxis is a serious allergic disease that may lead to death if
      not immediately recognized and treated. Triggers of anaphylaxis including food,
      drugs, and insect stings can vary widely. The incidence of anaphylaxis seems to
      be affected by age, sex, atopy, and geographic location. This study aims to
      examine the common triggers of anaphylaxis in Qatar. Methods: A total of 1068
      electronic medical records were audited using power chart system: 446 from the
      medical coding system of anaphylaxis and 622 from the epinephrine auto-injectors
      (EAIs) dispensed during January 2012-December 2017. Results: Of 1068 patients,
      574 (53.5%) had anaphylaxis; male to female ratio was 1.2, and 300 patients
      (77.9%) were less than 10 years old. The common triggers were food (n = 316,
      55.0%), insect stings (n = 161, 28.0%), and drugs (n = 103, 17.9%). Common
      anaphylaxis food triggers were nuts (n = 173, 30.1%), eggs (n = 89, 15.5%), and
      seafood (n = 72, 12.5%), and common anaphylaxis medication triggers were
      antibiotics (n = 49, 8.5%) and nonsteroidal anti-inflammatory drugs (n = 30,
      5.2%). Interestingly, 135 anaphylactic patients (23.5%) were due to black ant
      stings. The anaphylaxis triggers varied significantly between children and
      adults. Among children (less than 10 years), three quarters of the events were
      triggered by food (223, 74.3%) while among adults (20-55 years), insect stings (n
      = 59, 43.0%) and drugs (n = 44, 32.0%) were dominant. Discussion: This is the
      first national study stratifying anaphylaxis triggers among different age groups
      in Qatar. This study will serve as a guide for clinical practice in allergy
      clinics in Qatar and will help to assess future trends of anaphylaxis in Qatar.

PMID- 30214661
TI  - BRASSIERE CLASPS ARE A SOURCE OF NICKEL EXPOSURE.

PMID- 30214659
TI  - Allergy diagnosis from symptoms to molecules, or from molecules to symptoms: a
      comparative clinical study.
AB  - Background: Classical allergy diagnostic workup "from symptoms to molecules"
      comprises 1) clinical investigation, 2) skin prick- and IgE- testing, and
      recently, 3) molecular allergy testing. We aimed to examine the diagnostic
      fidelity of the alternative approach "from molecules to symptoms", which was
      recently suggested in the EAACI Molecular Allergology User's Guide, in a
      retrospective clinical study. Methods: Records from 202 patients with clinically
      suspected allergic sensitizations were extracted from files at two sites applying
      either the "ISAC-first" workup with IgE-testing by immuno-solid phase allergen
      chip ISAC112 followed by selected skin prick tests (SPT) or the "SPT-first"
      starting with SPT followed by the microarray test. Results: In the ISAC-first
      procedure significantly less SPTs were performed during allergy diagnosis (median
      4 vs. 14). By SPT in 19% of patients in the ISAC-first group and in 34% in the
      SPT-first group additional respiratory allergens (p = 0.014) were detected not
      positive in ISAC microarray. By ISAC microarray test 18% additional
      sensitizations were found in the ISAC-first, and 32% in SPT-first cohort (p =
      0.016). For food allergens 13 and 12% additional sensitizations were detected by
      the microarray not detected by SPT in the two groups (p = 0.800). No additional
      food allergen was found by SPT in the ISAC-first group, while in 6% of the cases
      in the SPT-first group detected sensitizations were negative in the microarray.
      Discussion: The ISAC-first approach followed by (fewer) SPTs meets the demands
      for a patient's tailored diagnostic work-up and therefore can be considered
      equivalent to the conventional way using the skin prick test as first screening
      tool, followed by IgE diagnosis. Conclusions: For the diagnostic verification of
      clinically suspected allergy, the novel concept "from molecules to clinic" offers
      a reliable diagnostic workup in shorter time. Due to lower skin test numbers it
      is especially applicable for young children and seniors, in atopic patients, and
      whenever skin tests get difficult or unreliable.

PMID- 30214660
TI  - Exploring physical activity engagement in secondary school students in
      Montevideo, Uruguay: A qualitative study.
AB  - Physical activity provides multiple health and educational benefits to children
      and youth, yet the majority of young people across the globe, including
      adolescents in Uruguay, do not participate in sufficient physical activity. This
      study aims to further inform intervention efforts for promoting adolescent
      physical activity in Uruguay by exploring physical activity perceptions and
      practices as well as physical activity barriers and opportunities in a sample of
      public and private secondary school students living in and around Montevideo,
      Uruguay. A total of n=65 secondary school students, ranging in age from 11 to 15
      years, participated in 12 focus groups. Despite generally favorable attitudes
      expressed by participants toward physical activity and identification of common
      physical activities, findings indicated several barriers for physical activity
      engagement in this sample of Uruguayan secondary school students -- which often
      vary by gender and SES, including: lack of access and availability of physical
      activity opportunities both within and outside of school time, lack of places as
      well as equipment and infrastructure for engagement in physical activity, and
      lack of time and competing activities such as video games. Key themes related to
      the importance of the social context for physical activity- especially for girls,
      as well as opportunities for physical activity, including the need for more
      afterschool programming, were also documented. These findings provide further
      context for understanding adolescent physical activity in Uruguay as well as
      direction for future intervention efforts.

PMID- 30214662
TI  - Vitamin D Deficiency, Skin Phototype, Sun Index, and Metabolic Risk Among
      Patients with High Rates of Sun Exposure Living in the Tropics.
AB  - Objective: We sought to evaluate serum 25-hydroxycholecalciferol (vitamin D [25
      OHD]) levels, skin phototype, and sun index in a sample of patients to determine
      the association between these factors and metabolic risk. Design: This was a
      cross-sectional study involving 729 adults (50.2% male). Mean age was 65.13+/
      9.18 years, sun index 5.71+/-5.06, body mass index (BMI) 27.60+/-5.34 kg/m2, and
      waist circumference 97.29+/-12.08cm. Hypertension, metabolic syndrome, and Type 2
      diabetes were reported in 77.8, 74.5, and 38.9 percent, respectively; Fitzpatrick
      Skin Types III and IV were reported in 60.6 percent. Results: Mean serum 25-OHD
      was 25.72+/-10.91ng/mL; 31 percent of subjects had serum 25-OHD below 20ng/mL,
      and 63.1 percent had serum 25-OHD below 30ng/mL. Although there were no
      significant differences between the vitamin D deficient and sufficient groups
      regarding age, BMI, waist circumference, or presence of diabetes, in the group
      with 25-OHD less than 20ng/mL (sun index of 4.5+/-4.08), higher serum
      triglycerides and lower high-density lipoprotein cholesterol (HDL-C) levels were
      measured: triglycerides 179.14+/-103.53 versus 161.63+/-90.23mg/dL (p=0.029) and
      HDL-C 43.48+/-12.38 versus 45.94+/-14.14mg/dL (p=0.018) compared to the group
      with 25-OHD levels of 20ng/mL or higher (sun index: 6.25+/-5.36). Considering
      less than 25th percentile (25-OHD: 18.7ng/mL) and 75th percentile or higher (25
      OHD: 30.8 ng/mL), the differences in serum triglycerides remained significant:
      176.63+/-103.79 versus 157.47+/-80.49 (p=0.039). Conclusion: We found a high
      prevalence of vitamin D deficiency in individuals with high sun exposure,
      regardless of age, BMI, and waist circumference. This deficiency was associated
      with increased serum triglycerides and decreased HDL-C levels.

PMID- 30214663
TI  - A Practical Approach to Chemical Peels: A Review of Fundamentals and Step-by-step
      Algorithmic Protocol for Treatment.
AB  - Background: Chemoexfoliation, also known as chemical peeling, is a method of
      targeted cutaneous ablation using specific caustic agents that allow for rapid,
      predictable, and uniform thickness of chemoablation to a desired cutaneous depth,
      ultimately resulting in an improved appearance of skin. Objective: In this
      review, we provide an up-to-date analysis of all currently available chemical
      peels for dermatologic use, as well as a step-by-step instructional protocol for
      an algorithmic approach to treatment. Methods: A comprehensive search of the
      Cochrane Library, MEDLINE, and PUBMED databases was performed to identify
      relevant literature investigating chemical peeling agents. In addition, a search
      of all commercially available, prescription-based peeling agents was performed to
      identify all products currently available in the United States market. Results
      and Conclusion: Chemical peels are the third most commonly performed noninvasive
      cosmetic procedure in the United States, with over 1,300,000 procedures performed
      in 2016 alone. There has been a paradigm shift in recent years, with lasers
      largely supplanting deep peels. Despite this shift, superficial peels have
      proliferated in both popularity and product diversity. When used for the
      appropriate indication and with proper technique, nearly all peeling agents have
      demonstrated excellent clinical efficacy and remain an indispensable cost
      effective tool in the dermatologist's aesthetic toolbox.

PMID- 30214664
TI  - Safety and Effectiveness of an Automated Microneedling Device in Improving the
      Signs of Aging Skin.
AB  - Objective: The purpose of this study was to evaluate the efficacy and safety of
      an automated microneedling device (Exceed, Amiea Med, MT.DERM GmbH, Berlin,
      Germany) when used for the rejuvenation of facial skin, as well as to generate
      data for an FDA 510K submission for the device. Study design: This was an open
      label, single-center study. Participants: Forty-eight subjects aged 35 to 75
      years with signs of facial skin aging were recruited. After consenting and
      satisfying inclusion criteria, each subject underwent four microneedling sessions
      30 days apart. Subjects were assessed at baseline and at 30, 60, 90, and 150 days
      after the first treatment. Measurements: Wrinkles were assessed using the
      Lemperle Grading Scale. Skin laxity and texture were assessed using a modified
      Alexiades-Armenakas Grading Scale. Digital fringe projection technology (PRIMOS)
      was used to determine skin topography of the periorbital and mesolabial areas.
      Results: Mean improvements in global wrinkle score (mean of nine facial area
      grades), skin laxity, and skin texture at Day 150, compared to baseline were 1.23
      (99% confidence interval [CI]: 1.11, 1.34), 1.09 (99% CI: 0.93, 1.26), and 1.54
      (99% CI: 1.33, 1.75), respectively. Statistically significant mean improvements
      in these three measures were also observed at Day 90. Improvements in wrinkle
      grading and skin texture were confirmed by the PRIMOS profilometry. The treatment
      was well tolerated with minimal pain, discomfort, and downtime. Side effects were
      minor and easily managed. Conclusion: This study demonstrates that four
      microneedling treatments of facial skin, spaced four weeks apart, significantly
      improve lines, wrinkles, skin laxity and skin texture, 90 and 150 days after the
      first treatment. The treatment was well tolerated with minimal pain, discomfort,
      and downtime. Side effects were minor and easily managed compared to other
      invasive technologies, such as laser ablation and radiofrequency.

PMID- 30214665
TI  - The 12-point Revitalization Guide to Pan-facial Application of Injectable Fillers
      in Older Women.
AB  - Soft tissue filler augmentation for beautification is a common aesthetic request
      from women who wish to enhance facial features. These interventions are performed
      in both younger and older women and can result in exaggerated or over-augmented
      lips and cheeks. This unsatisfactory outcome in older women might be due to the
      inappropriate application of filler enhancement principles that are based the
      characteristics of a young face. These existing principles do not necessarily
      translate well to an older face due to underlying facial skeletal changes
      associated with aging. Mature women might prefer subtler corrections that do not
      significantly alter their faces, but rather refresh and revitalize their current
      appearance. Here, the author presents a 12-point revitalization guide, based on
      personal experience, as an approach for the pan-facial application of calcium
      hydroxylapatite and hyaluronic acid fillers specific to the aging female face
      that can result in an understated and age-appropriate appearance. Three
      illustrative cases are also presented.

PMID- 30214666
TI  - Non-insulated Fractional Microneedle Radiofrequency Treatment with Smooth Motor
      Insertion for Reduction of Depressed Acne Scars, Pore Size, and Skin Texture
      Improvement: A Preliminary Study.
AB  - Background: Severe scarring caused by acne is associated with substantial
      physical and psychological distress, both in adolescents and adults. There are
      two basic types of scars: atrophic (depressed) and raised (hypertrophic).
      Microneedle fractional radiofrequency (MFRF) is a new technology that uses extra
      sharp microneedles to heat the depths of the dermis, which promotes dermal
      collagen remodeling. In this study, we used electronically controlled non
      insulated microneedle radiofrequency treatment to treat atrophic acne scars,
      improve skin texture, and reduce pore size. Methods: Nineteen patients were
      enrolled in the study. The goal of the treatment was to improve acne scars and
      skin texture and to reduce pore size. Each patient received 2 to 6 treatments
      with one month intervals between treatments. Treated areas were visually assessed
      for skin response, including edema, erythema, and burns. We used the standard
      pain scale of 0 to 10 to assess pain during and after treatment. Results: All the
      patients completed a series of 2 to 6 treatments. No adverse events as burns,
      scarring, or hyper/hypopigmentation were reported. Subjective pain assessment was
      the average point of 1.5, as reported by the patients. The subjective and
      objective questionnaire revealed high satisfaction from the treatment.
      Conclusions: The presented study results show that the MFRF treatment provides a
      highly effective minimally invasive treatment for acne scars, skin texture
      improvement, and pore size reduction, with a short downtime and high subjective
      satisfaction rates.

PMID- 30214667
TI  - Management of Truncal Acne Vulgaris with Topical Dapsone 7.5% Gel.
AB  - The majority of available data on the prevalence, grading, and management of acne
      vulgaris (AV) are based on studies that evaluate facial AV. Data are limited in
      all of these areas with truncal AV. This study evaluates the efficacy and safety
      of topical management of truncal AV involving the chest and back in a three
      center, open-label, 16-week study. Enrolled subjects (N=20), 12 years of age or
      older, applied dapsone 7.5% gel once daily as monotherapy. The primary endpoint
      of the study was the percent of subjects who achieved a two-grade improvement and
      a rating of clear or almost clear based on the Investigator Global Assessment
      scale. Secondary endpoints included percent reductions of inflammatory, non
      inflammatory (comedonal), and total lesions at Week 16 compared to baseline.
      Tolerability and safety were assessed over the duration of the study.

PMID- 30214668
TI  - A Randomized, Active Comparator-controlled Clinical Trial of a Topical Botanical
      Cream for Skin Hydration, Elasticity, Firmness, and Cellulite.
AB  - Background: The skin is where initial visual signs of aging manifest, including
      increased skin dryness and decreased firmness and elasticity. Cellulite, a skin
      condition characterized by changes in the skin morphology due to excessive lipid
      deposition in subcutaneous adipose tissue, is another characteristic of skin
      aging. Objective: We sought to assess the effectiveness of a topical botanical
      cream on cellulite, skin hydration, firmness, and elasticity after two, four, and
      eight weeks of use compared to an active comparator. Design: The study was a
      single-blind, randomized, controlled study conducted on subjects with mild-to
      severe cellulite on the thighs. Subjects were treated with a topical botanical
      cream (UP1307) and an active comparator for eight weeks. A total of 44 women 18
      to 59 years of age were enrolled. Test products were gently applied in a circular
      motion to the area identified by subjects as the target cellulite area twice per
      day. Measurements: Measurements using Corneometer(r) (for skin hydration) and
      Cutometer(r) (for skin elasticity and firmness) were carried out at each visit in
      addition to expert clinical grader evaluations for cutaneous changes and
      cellulite. Outcomes were also assessed by patients using subject questionnaires.
      Results: Patients reported significant improvement in skin hydration, firmness,
      and elasticity over time. Findings were corroborated with objective instrumental
      measurements. At Week 8, 44.4- and 42.7-percent improvement in appearance of
      cellulite was also observed for the UP1307 cream and the active comparator group,
      respectively. Conclusion: Use of UP1307 cream produced significant improvements
      in skin hydration, firmness, and elasticity, with associated improvement in
      cellulite appearance. There was overall superiority of UP1307 between groups.
      Progressive subject perceptions of product effects are reported.

PMID- 30214670
TI  - SOD1 stimulates lamellipodial protrusions in Neuro 2A cell lines.
AB  - We here investigated the effects of overexpressed superoxide dismutase (SOD)1 and
      amyotrophic lateral sclerosis (ALS)-linked SOD1 mutants G93A and G147S in Neuro
      2A (N2A) cell lines, and found a three-fold increase in lamellipodia either in
      cells cultured under differentiated or undifferentiated growth conditions. In
      undifferentiated N2A cells, SOD1 constructs promoted lamellipodial protrusions to
      similar extent as the overexpression of Rac1, and SOD1-mediated lamellipodia were
      prevented by coexpression of the N17 dominant-negative form of Rac1, or shRNA for
      a downstream effector of Rac1, the insulin receptor tyrosine kinase substrate p53
      (IRSp53) or its binding partner LIN7. Moreover, no additive effect was measured
      by coexpression of the SOD1 constructs with Rac1, IRSp53 or LIN7. Collectively
      these data support a role for SOD1 in the regulation of Rac1-mediated
      lamellipodia pathway, a property fully retained by the two SOD1 mutants.

PMID- 30214669
TI  - Tropoelastin: A novel marker for plaque progression and instability.
AB  - Background: Elastolysis and ineffective elastogenesis favor the accumulation of
      tropoelastin, rather than cross-linked elastin, in atherosclerotic plaques. We
      developed gadolinium-labeled tropoelastin-specific magnetic resonance contrast
      agents (Gd-TESMAs) for tropoelastin imaging in animal models. Methods and
      Results: Two peptides, VVGSPSAQDEASPLS and YPDHVQYTHY were selected to target
      tropoelastin. In vitro binding, relaxivity, and biodistribution experiments
      enabled characterization of the probes and selecting the best candidate for in
      vivo MRI. MRI was performed in atherosclerotic apolipoprotein E-deficient (ApoE-/
      ) mice and New Zealand white rabbits with stable and rupture-prone plaques using
      Gd-TESMA. Additionally, human carotid endarterectomy specimens were imaged ex
      vivo. The VVGSPSAQDEASPLS-based probe discriminated between tropoelastin and
      cross-linked elastin (64+/-7% vs 1+/-2%, P=0.001), had high in vitro relaxivity
      in solution (r1-free=11.7+/-0.6mM-1s-1, r1-bound to tropoelastin = 44+/-1mM-1s-1)
      and favorable pharmacokinetics. In vivo mice vascular enhancement (4wks=0.13+/
      0.007mm2, 8wks=0.22+/-0.01mm2, 12wks=0.33+/-0.01mm2, P<0.001) and R1 relaxation
      rate (4wks=0.90+/-0.01 s-1, 8wks=1.40+/-0.03 s-1, 12wks=1.87+/-0.04s-1, P<0.001)
      increased with atherosclerosis progression after Gd-TESMA injection. Conversely,
      statin-treated (0.13+/-0.01mm2, R1 =1.37+/-0.03s-1) and control (0.10+/-0.005mm2,
      R1 =0.87+/-0.05s-1) mice showed less enhancement. Rupture-prone rabbit plaques
      had higher R1 relaxation rate compared with stale plaques (R1=2.26+/-0.1s-1vs
      R1=1.43+/-0.02s-1, P=0.001), after administration of Gd-TESMA that allowed
      detection of rupture-prone plaques with high sensitivity (84.4%) and specificity
      (92.3%). Increased vascular R1 relaxation rate was observed in carotid
      endarterectomy plaques after soaking (R1pre= 1.1+/-0.26 s-1 vs R1post= 3.0+/-0.1s
      1, P=0.01). Ex vivo analyses confirmed the MRI findings and showed uptake of the
      contrast agent to be specific for tropoelastin. Conclusions: MRI of tropoelastin
      provides a novel biomarker for atherosclerotic plaque progression and
      instability.

PMID- 30214672
TI  - Leaf trichomes affect caterpillar feeding in an instar-specific manner.
AB  - Leaf trichomes play well-established roles in defense against insect herbivores,
      both as a physical barrier that impedes herbivore movement and by mediating
      chemical defenses. However, little work has examined how different trichome types
      influence herbivory by herbivores at different stages of development. We examined
      whether caterpillar instar and trichome type (glandular or non-glandular)
      affected the ability of the specialist herbivore caterpillar Manduca sexta to
      initiate feeding on 11 Solanaceous species exhibiting variation in the density
      and type of leaf trichomes. Our results suggest that non-glandular trichomes are
      far more effective than glandular trichomes in deterring the initiation of
      feeding by first- and second-instar caterpillars. Meanwhile, neither glandular
      nor non-glandular trichomes significantly affected the ability of third-instar
      caterpillars to commence feeding. These findings suggest that while non-glandular
      trichomes deter feeding initiation by early instar caterpillars, the contribution
      of both trichomes on later instars may depend on effects after feeding
      initiation.

PMID- 30214671
TI  - Mapping of quantitative trait loci related to primary rice root growth as a
      response to inoculation with Azospirillum sp. strain B510.
AB  - Azospirillum sp. strain B510 has been known as the plant growth-promoting
      endophyte; however, the growth-promotion effect is dependent on the plant
      genotype. Here, we aimed to identify quantitative trait loci (QTL) related to
      primary root length in rice at the seedling stage as a response to inoculation
      with B510. The primary root length of "Nipponbare" was significantly reduced by
      inoculation with B510, whereas that of "Kasalath" was not affected. Thus, we
      examined 98 backcrossed inbred lines and four chromosome segment substitution
      lines (CSSL) derived from a cross between Nipponbare and Kasalath. The primary
      root length was measured as a response to inoculation with B510, and the relative
      root length (RRL) was calculated based on the response to non-inoculation. Three
      QTL alleles, qRLI-6 and qRLC-6 on Chromosome (Chr.) 6 and qRRL-7 on Chr. 7
      derived from Kasalath increased primary root length with inoculation (RLI),
      without inoculation, (RLC) and RRL and explained 20.2%, 21.3%, and 11.9% of the
      phenotypic variation, respectively. CSSL33, in which substitution occurred in the
      vicinity region of qRRL-7, showed a completely different response to inoculation
      with B510 compared with Nipponbare. Therefore, we suggest that qRRL-7 might
      strongly control root growth in response to inoculation with Azospirillum sp.
      strain B510.

PMID- 30214673
TI  - Involvement of S-type anion channels in disease resistance against an oomycete
      pathogen in Arabidopsis seedlings.
AB  - Pharmacological indications suggest that anion channel-mediated plasma membrane
      (PM) anion efflux is crucial in early defense signaling to induce immune
      responses and programmed cell death in plants. Arabidopsis SLAC1, an S-type anion
      channel required for stomatal closure, is involved in cryptogein-induced PM Cl-
      efflux to positively modulate the activation of other ion fluxes, production of
      reactive oxygen species and a wide range of defense responses including
      hypersensitive cell death in tobacco BY-2 cells. We here analyzed disease
      resistance against several pathogens in multiple mutants of the SLAC/SLAH
      channels of Arabidopsis. Resistance against a biotrophic oomycete
      Hyaloperonospora arabidopsidis Noco2 was significantly enhanced in the SLAC1
      overexpressing plants than in the wild-type, while that against a bacteria
      Pseudomonas syringae was not affected significantly. Possible regulatory roles of
      S-type anion channels in plant immunity and disease resistance against bacterial
      and oomycete pathogens is discussed.

PMID- 30214674
TI  - Senomic view of the cell: Senome versus Genome.
AB  - In the legacy of Thomas Henry Huxley, and his 'epigenetic' philosophy of biology,
      cells are proposed to represent a trinity of three memory-storing media: Senome,
      Epigenome, and Genome that together comprise a cell-wide informational
      architecture. Our current preferential focus on the Genome needs to be
      complemented by a similar focus on the Epigenome and a here proposed Senome,
      representing the sum of all the sensory experiences of the cognitive cell and its
      sensing apparatus. Only then will biology be in a position to embrace the whole
      complexity of the eukaryotic cell, understanding its true nature which allows the
      communicative assembly of cells in the form of sentient multicellular organisms.

PMID- 30214676
TI  - Glycine is able to induce both a motility speed in- and decrease during zebrafish
      neuronal migration.
AB  - Various neurotransmitters influence neuronal migration in the developing
      zebrafish hindbrain. Migrating tegmental hindbrain nuclei neurons (THNs) are
      governed by depolarizing neurotransmitters (acetylcholine and glutamate), and
      glycine. In mature neurons, glycine binds to its receptor to hyperpolarize cells.
      This effect depends on the co-expression of the solute carrier KCC2. Immature
      precursors, however, typically express NKCC1 instead of KCC2, leading to membrane
      depolarization upon glycine receptor activation. As neuronal migration occurs in
      neurons after leaving the cell cycle and before terminal differentiation, we
      hypothesized that the switch from NKCC1 to KCC2 expression could alter the effect
      of glycine on THN migration. We tested this notion using in vivo cell tracking,
      overexpression of glycine receptor mutations and whole mount in situ
      hybridization. We summarize our findings in a speculative model, combining
      developmental age, glycine receptor strength and solute carrier expression to
      describe the effect of glycine on the migration of THNs.

PMID- 30214677
TI  - Black tea differs from green tea: it suppresses long-term memory formation in
      Lymnaea.
AB  - Foods, such as Green tea (GT), containing the flavonol, (-)-Epicatechin (Epi),
      enhance the formation of long-term memory (LTM) when snails are operantly
      conditioned in that substance. That is, a single 0.5 h training session results
      in LTM; whereas similar training in pond water does not result in LTM. It was of
      interest to determine if Black tea (BT), which is a more popular beverage than GT
      and which is derived from the same tea leaves, also enhances LTM formation. We
      found that BT, unlike GT, depressed homeostatic aerial respiratory behaviour and
      obstructed LTM formation. We used two different methods to determine if BT
      altered LTM formation and both procedures showed us that BT obstructed LTM
      formation. We conclude that BT obstructs LTM formation and depresses homeostatic
      aerial respiration.

PMID- 30214675
TI  - On plant defense signaling networks and early land plant evolution.
AB  - All land plants must cope with phytopathogens. Algae face pathogens, too, and it
      is reasonable to assume that some of the strategies for dealing with pathogens
      evolved prior to the origin of embryophytes - plant terrestrialization simply
      changed the nature of the plant-pathogen interactions. Here we highlight that
      many potential components of the angiosperm defense toolkit are i) found in
      streptophyte algae and non-flowering embryophytes and ii) might be used in non
      flowering plant defense as inferred from published experimental data.
      Nonetheless, the common signaling networks governing these defense responses
      appear to have become more intricate during embryophyte evolution. This includes
      the evolution of the antagonistic signaling pathways of jasmonic and salicylic
      acid, multiple independent expansions of resistance genes, and the evolution of
      resistance gene-regulating microRNAs. Future comparative studies will illuminate
      which modules of the streptophyte defense signaling network constitute the core
      and which constitute lineage- and/or environment-specific (peripheral) signaling
      circuits.

PMID- 30214678
TI  - Childhood Maltreatment and HIV Risk-Taking among Men Using the Internet
      Specifically to Find Partners for Unprotected Sex.
AB  - Purpose: Using a Syndemics Theory conceptual model, this study examines the
      relationship between childhood maltreatment experiences and involvement in HIV
      risk taking in a sample of adult men who actively seek partners for unprotected
      sex via the Internet. One of the main advantages to using this theoretical model
      is that it considers the co-varying influences of factors such as childhood
      maltreatment, psychological/psychosocial functioning, risk-related preferences,
      demographic characteristics, substance use/abuse, and attitudes toward risk
      taking on actual risk practices. Methods: The study was based on a national
      random sample of 332 MSM who use the Internet to seek men with whom they can
      engage in unprotected sex. Data collection was conducted via telephone interviews
      between January 2008 and May 2009. Structural equation analysis was undertaken to
      examine the specific nature of the relationships involved in understanding HIV
      risk practices. Results: Childhood maltreatment experiences were not found to be
      related directly to involvement in HIV risk taking in adulthood. Childhood
      maltreatment, particularly in the form of emotional neglect, was found to be an
      important variable in the overall structural equation. Its effect on HIV risk
      taking was indirect, operating principally by having a negative impact upon self
      esteem, which in turn had a negative effect on attitudes toward condom use, which
      in turn were related strongly and directly to risk taking. Conclusions: Childhood
      maltreatment experiences are relevant to understanding HIV risk practices among
      MSM in adulthood, but the relationship is not as simple as usually
      conceptualized. Rather, childhood maltreatment appears to impact risk taking
      indirectly, through its effects on mental health functioning, which in turn
      affects risk-related attitudes.

PMID- 30214679
TI  - Rituximab mechanisms of action in B-CLL: a new piece of the puzzle.

PMID- 30214680
TI  - Acquired palbociclib resistance in KRAS-mutant lung cancer.

PMID- 30214682
TI  - A novel, nontoxic iron chelator, super-polyphenol, effectively induces apoptosis
      in human cancer cell lines.
AB  - Iron chelation therapy is the main treatment for iron overload disease. Iron
      chelators were recently reported to be useful for cancer therapy; however, they
      cause side effects that make them difficult to use in some cancer patients. Thus,
      a novel oral iron chelator, super-polyphenol (SP), was developed for cancer
      therapy to decrease the side effects. SP is either water soluble or insoluble,
      and has different isoforms according to the number of side chains. Of these
      isoforms, water-soluble SP6 and SP10 appear to be the best candidates, as they
      have the strongest chelating abilities. In this study, we focused on the
      usefulness and safety of SP6 and SP10 as anti-cancer drugs, and examined their
      anti-cancer effects and toxicity. The results showed that SP6 and SP10 inhibited
      cancer cell proliferation by inducing apoptosis in HCT116, HSC-2, A549, and MCF-7
      cancer cells. SP10 also inhibited tumor growth in an HCT116 xenograft model. SP6
      and SP10 had no acute toxicities. An intravenous injection test revealed that SP6
      and SP10 had better safety profiles than the iron chelator deferoxamine. In
      conclusion, SP is a novel oral iron chelator with anti-cancer effects and few
      adverse side effects. This is the first report of SP in the literature.

PMID- 30214681
TI  - PKCiota and YAP1 are crucial in promoting pancreatic tumorigenesis.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignant disease with 5-year
      survival rate of less than 6%. Activating mutations of Kras (mu-Kras) are often
      detected in most of PDAC patients. Although it has been known that oncogenic Kras
      is the driver of pancreatic cancer initiation and development, the underlying
      mechanisms by which mu-Kras promotes PDAC remain poorly understood. Here, we
      identify that PKCiota is one of the crucial factors for supporting the survival
      of pancreatic cancer cells expressing mu-Kras. Our study demonstrates that after
      the knockdown of PKCiota, the expression of the transcriptional co-activator YAP1
      is decreased, which hinders the expression of the downstream target gene Mcl-1,
      and subsequently sensitizes pancreatic cancer MiaPaCa and PANC-1 cells experssing
      mu-Kras to apoptosis. In comparison, the suppression of PKCiota has little impact
      on the viability of non-neoplastic pancreatic HPDE6-C7 cells. Moreover, the
      transient overexpression of oncogenic Kras in HPDE6-C7 elevates the expression of
      PKCiota and YAP1 concomitantly. The upregulated YAP1 in HPDE6-C7/ mu-Kras cells
      is abolished once PKCiota is suppressed, suggesting the linear relationship among
      mu-Kras, PKCiota and YAP1. This phenomenon is further proven by the co
      upregulation of PKCiota and YAP1 in HPDE6-C7 cells stably transfected with mu
      Kras. Taken together, our findings suggest that PKCiota acts through promoting
      YAP1 function to promote the survival of pancreatic cancer cells expressing mu
      Kras. It appears that targeting PKCiota-YAP1 signaling is a feasible strategy for
      developing new therapeutics for treating pancreatic cancer patients.

PMID- 30214683
TI  - Differential signaling pathway activation in 7,12-dimethylbenz[a] anthracene
      (DMBA)-treated mammary stem/progenitor cells from species with varying mammary
      cancer incidence.
AB  - A natural variation exists in the susceptibility to mammary cancer among wild and
      domestic mammalian species. Mammary stem/progenitor cells (MaSC) represent a
      primary target cell for transformation; however, little is known about the
      intrinsic response of these cells to carcinogenic insults. Polycyclic aromatic
      hydrocarbons (PAH), such as 7,12-dimethylbenz[a]anthracene (DMBA), are abundantly
      present in the environment and have been linked to the development of mammary
      cancer in humans and rodents. We treated MaSC from equine (mammary cancer
      resistant) and canine (mammary cancer-susceptible) species with DMBA and assessed
      cytochrome P450 metabolic activity, DNA damage and viability. Our notable
      findings were that MaSC from both species showed DNA damage following DMBA
      treatment; however, equine MaSC initiated cell death whereas canine MaSC repaired
      this DNA damage. Follow-up studies, based on genome-wide transcriptome analyses,
      revealed that DMBA induced activation of both the intrinsic and extrinsic
      apoptotic pathways in equine, but not canine, MaSC. Based on these findings, we
      propose a hypothetical model in which undergoing apoptosis in response to an
      oncogenic event might contribute to a lower incidence of mammary cancer in
      certain mammalian species. Such a mechanism would allow for the elimination of
      DNA-damaged MaSC, and hence, reduce the risk of potential tumor-initiating
      mutations in these cells.

PMID- 30214684
TI  - PLAGL1 gene function during hepatoma cells proliferation.
AB  - Hepatocellular carcinoma develops as a multistep process, in which cell cycle
      deregulation is a central feature, resulting in unscheduled proliferation. The
      PLAGL1 gene encodes a homonym zinc finger protein that is involved in cell
      proliferation control. We determined the genomic profile and the transcription
      and expression level of PLAGL1, simultaneously with that of its molecular
      partners p53, PPARgamma and p21, in cell-lines derived from patients with liver
      cancer, during in vitro cell growth. Our investigations revealed that genomic and
      epigenetic changes of PLAGL1 are also present in hepatoma cell-lines.
      Transcription of PLAGL1 in tumor cells is significantly lower than in normal
      fibroblasts, but no significant differences in terms of protein expression were
      detected between these two cell-types, indicating that there is not a direct
      relationship between the gene transcriptional activity and protein expression. RT
      PCR analyses on normal fibroblasts, used as control, also showed that PLAGL1 and
      p53 genes transcription occurs as an apparent orchestrated process during normal
      cells proliferation, which gets disturbed in cancer cells. Furthermore, abnormal
      trafficking of the PLAGL1 protein may occur in hepatocarcinogenesis.

PMID- 30214685
TI  - Thymic stromal lymphopoietin in human pancreatic ductal adenocarcinoma:
      expression and prognostic significance.
AB  - Thymic stromal lymphopoietin (TSLP) has emerged as an important, but
      contradictory, player conditioning tumor growth. In certain contexts, by driving
      T helper (h) 2 responses via tumor-associated OX40 Ligand (OX40L)+ dendritic
      cells (DCs), TSLP may play a pro-tumorigenic role. The study elucidates the
      importance of TSPL in pancreatic ductal adenocarcinoma (PDAC), by analyzing: i)
      TSLP levels in PDAC cell-line supernatants and plasma from patients with locally
      advanced/metastatic PDAC, pre- and post-treatment with different chemotherapeutic
      protocols, in comparison with healthy donors; ii) TSLP and OX40L expression in
      PDAC and normal pancreatic tissues, by immunohistochemistry; iii) OX40L
      expression on ex vivo-generated normal DCs in the presence of tumor-derived TSLP,
      by flow cytometry; iv) clinical relevance in terms of diagnostic and prognostic
      value and influence on treatment modality and response. Some PDAC cell lines,
      such as BxPC-3, expressed both TSLP mRNA and protein. Normal DCs, generated ex
      vivo in the presence of TSLP-rich-cell supernatants, displayed increased
      expression of OX40L, reduced by the addition of a neutralizing anti-TSLP
      polyclonal antibody. OX40L+ cells were detected in pancreatic tumor inflammatory
      infiltrates. Abnormally elevated TSLP levels were detected in situ in tumor cells
      and, systemically, in locally-advanced/metastatic PDAC patients. Of the
      chemotherapeutic protocols applied, gemcitabine plus oxaliplatin (GEMOX)
      significantly increased circulating TSLP levels. Elevated plasma TSLP
      concentration was associated with shorter overall survival and increased risk of
      poor outcome. Plasma TSLP measurement successfully discriminated PDAC patients
      from healthy controls. These data show that TSLP secreted by pancreatic cancer
      cells may directly impact PDAC biology and patient outcome.

PMID- 30214686
TI  - Bladder cancer detection by urinary extracellular vesicle mRNA analysis.
AB  - Objective: Urinary extracellular vesicles (EV) could be promising biomarkers for
      urological diseases. In this retrospective feasibility study, we conducted
      biomarker screening for early stage bladder cancer using EV mRNA analysis.
      Methods: Biomarker candidates were identified through RNA-seq analysis of urinary
      EV from patients with non-muscle invasive bladder cancer (N=3), advanced
      urothelial cancer (N=3), no residual tumor after TURBT (N=2), and healthy and
      disease controls (N=4). Diagnostic performance was evaluated by RT-qPCR in a
      larger patient group including bladder cancer (N=173), renal pelvis and ureter
      cancer (N=33), no residual tumor and non-cancer disease control (N=36). Results:
      Urinary EV SLC2A1, GPRC5A and KRT17 were overexpressed in pT1 and higher stage
      bladder cancer by 20.6-fold, 18.2-fold and 29.5-fold, respectively. These genes
      allowed detection of non-muscle invasive bladder cancer (AUC: 0.56 to 0.64 for
      pTa, 0.62 to 0.80 for pTis, and 0.82 to 0.86 for pT1) as well as pT2 and higher
      muscle invasive bladder cancer (AUC: 0.72 to 0.90). Subgroup analysis indicated
      that these markers could be useful for the detection of cytology-negative/
      suspicious and recurrent bladder cancers. Conclusion: Three urinary EV mRNA were
      discovered to be elevated in bladder cancer. Urinary EV mRNA are promising
      biomarkers of urothelial cancer and worth further investigation.

PMID- 30214688
TI  - PAX5A and PAX5B isoforms are both efficient to drive B cell differentiation.
AB  - Pax5 is the guardian of the B cell identity since it primes or enhances the
      expression of B cell specific genes and concomitantly represses the expression of
      B cell inappropriate genes. The tight regulation of Pax5 is therefore required
      for an efficient B cell differentiation. A defect in its dosage can translate
      into immunodeficiency or malignant disorders such as leukemia or lymphoma. Pax5
      is expressed from two different promoters encoding two isoforms that only differ
      in the sequence of their first alternative exon. Very little is known regarding
      the role of the two isoforms during B cell differentiation and the regulation of
      their expression. Our work aims to characterize the mechanisms of regulation of
      the expression balance of these two isoforms and their implication in the B cell
      differentiation process using murine ex vivo analyses. We show that these two
      isoforms are differentially regulated but have equivalent function during early B
      cell differentiation and may have functional differences after B cell activation.
      The tight control of their expression may thus reflect a way to finely tune Pax5
      dosage during B cell differentiation process.

PMID- 30214687
TI  - Vitamin C promotes decitabine or azacytidine induced DNA hydroxymethylation and
      subsequent reactivation of the epigenetically silenced tumour suppressor CDKN1A
      in colon cancer cells.
AB  - Epigenetic silencing of tumour suppressor genes is a key hallmark of colorectal
      carcinogenesis. Despite this, the therapeutic potential of epigenetic agents
      capable of reactivating these silenced genes remains relatively unexplored.
      Evidence has shown the dietary antioxidant vitamin C (ascorbate) acts as an
      inducer of the ten-eleven translocation (TET) dioxygenases, an enzyme family that
      catalyses a recently described mechanism of DNA demethylation linked to gene re
      expression. In this study, we set out to determine whether vitamin C can enhance
      the known anti-neoplastic actions of the DNA-demethylating agents decitabine
      (DAC) and azacytidine (AZA) in colorectal cancer cells. Administration of vitamin
      C alone significantly enhanced global levels of 5-hydroxymethyl-2'-deoxycytidine
      (5-hmdC), without altering 5-methyl-2'-deoxycytidine (5-mdC), as would be
      expected upon the activation of TET dioxygenases. Concomitant treatment of
      vitamin C with either AZA or DAC resulted in an unexpectedly high increase of
      global 5-hmdC levels, one that administration of any these compounds alone could
      not achieve. Notably, this was also accompanied by increased expression of the
      tumour suppressor p21 (CDKN1A), and a significant increase in apoptotic cell
      induction. Our in vitro data leads us to hypothesize that the reactivation of
      genes in colorectal cancer cells by AZA or DAC can be improved when the 5-hmdC
      levels are simultaneously increased by the TET activator vitamin C. The dual
      administration of demethylating agents and vitamin C to colorectal cancer
      patients, a demographic in which vitamin C deficiencies are common, may improve
      responses to epigenetic therapies.

PMID- 30214689
TI  - Beyond the 3'UTR binding-microRNA-induced protein truncation via DNA binding.
AB  - Here, we present a miR mechanism which is active in the nucleus and is essential
      for the production of intron included, C-terminal truncated and biologically
      active proteins, like e.g. Vim3. We exemplified this mechanism by miRs, miR-15a
      and miR-498, which are overexpressed in clear cell renal carcinoma or oncocytoma.
      Both miRs directly interact with DNA in an intronic region, leading to
      transcriptional stop, and therefore repress the full length version of the pre
      mRNA, resulting in intron included truncated proteins (Mxi-2 and Vim3). A
      computational survey shows that this miR:DNA interactions mechanism may be
      generally involved in regulating the human transcriptome, with putative
      interaction sites in intronic regions for over 1000 genes. In this work, an
      entirely new mechanism is revealed how miRs can repress full length protein
      translation, resulting in C-terminal truncated proteins.

PMID- 30214690
TI  - Identification of a novel gene fusion in ALT positive osteosarcoma.
AB  - The Alternative Lengthening of Telomeres (ALT) pathway stimulates telomere
      elongation and prevents cellular senescence in approximately 60% of osteosarcoma.
      While the precise mechanism underlying activation of the ALT pathway is unclear,
      mutations in the chromatin remodeling protein ATRX, histone chaperone DAXX, and
      the histone variant H3.3 correlate with ALT status. ATRX and DAXX facilitate
      deposition of the histone variant H3.3 within heterochromatic regions suggesting
      that loss of ATRX, DAXX, and/or H3.3 lead to defects in the stability of
      telomeric heterochromatin. Genetic mutations in ATRX, DAXX, and H3.3 have been
      detected in ALT positive cancers, however, a subset of ALT samples show loss of
      ATRX or DAXX protein expression or localization without evidence of genetic
      alterations suggesting additional uncharacterized defects in ATRX/DAXX/H3.3
      function. Here, using Next Generation Sequencing we identified a novel gene
      fusion event between DAXX and the kinesin motor protein, KIFC3, leading to the
      translation of a chimeric DAXX-KIFC3 fusion protein. Moreover, we demonstrate
      that the fusion of KIFC3 to DAXX causes defects in DAXX function likely promoting
      ALT activity. These data highlight a potentially unrecognized mechanism of DAXX
      inactivation in ALT positive osteosarcoma and provide rationale for thorough and
      comprehensive analyses of ATRX/DAXX/H3.3 proteins in ALT positive cancers.

PMID- 30214691
TI  - Correction: Increasing TIMP3 expression by hypomethylating agents diminishes
      soluble MICA, MICB and ULBP2 shedding in acute myeloid leukemia, facilitating NK
      cell-mediated immune recognition.
AB  - [This corrects the article DOI: 10.18632/oncotarget.16657.].

PMID- 30214692
TI  - Correction: The mutational landscape of ocular marginal zone lymphoma identifies
      frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP.
AB  - [This corrects the article DOI: 10.18632/oncotarget.14928.].

PMID- 30214693
TI  - Challenges to belief systems in the context of climate change adaptation.
AB  - This article focuses on the social aspects of climate change and explores the
      interrelationship between belief systems and adaptation. The links and
      interaction between external and internal realities are examined from the
      perspective of contextual vulnerability, with a focus on the multifaceted
      structure of belief systems. The aim was to determine those challenges regarding
      climate change adaptation that are caused by a community's belief system and to
      make recommendations to overcome them. Diverse perceptions of climate change and
      beliefs from three townships in the North-West Province of South Africa were
      collected and analysed using Q-methodology, finding five distinct worldview
      narratives. These narratives were named naturalist collectivist, religious,
      religious determinist, activist collectivist and structural thinker. It is
      recommended that policymakers aim to address diverse views and should be informed
      by factors that increase resistance to belief revision. Information should be
      framed in ways that foster the perception of internal control, are clearly
      evidence based and encourage a desire to learn more.

PMID- 30214694
TI  - Erratum: A political economy analysis of decision-making on natural disaster
      preparedness in Kenya.
AB  - [This corrects the article DOI: 10.4102/jamba.v10i1.497.].

PMID- 30214695
TI  - Intermediate Levels of Antibiotics May Increase Diversity of Colony Size
      Phenotype in Bacteria.
AB  - Antibiotics select for resistant bacteria whose existence and emergence is more
      likely in populations with high phenotypic and genetic diversity. Identifying the
      mechanisms that generate this diversity can thus have clinical consequences for
      drug-resistant pathogens. We show here that intermediate levels of antibiotics
      are associated with higher levels of phenotypic diversity in size of colony
      forming units (cfus), within a single bacterial population. We examine
      experimentally thousands of populations of bacteria subjected to different
      disturbance levels that are created by varying antibiotic concentrations. Based
      on colony sizes, we find that intermediate levels of antibiotics always result in
      the highest phenotypic variation of this trait. This result is supported across
      bacterial densities and in the presence of three different antibiotics with two
      different mechanisms of action. Our results suggest intermediate levels of a
      stressor (as opposed to very low or very high levels) could affect the phenotypic
      diversity of a population, at least with regards to the single trait measured
      here. While this study is limited to a single phenotypic trait within a single
      species, the results suggest examining phenotypic and genetic variation created
      by disturbances and stressors could be a promising way to understand and limit
      variation in pathogens.

PMID- 30214696
TI  - Assessment of tumor necrosis factor alpha (TNFalpha) and interleukin 6 level in
      gingival crevicular fluid during orthodontic tooth movement: a randomized split
      mouth clinical trial.
AB  - Background: Orthodontic tooth movement (OTM) is based on induction of periodontal
      tissue remodeling. Mechanical tooth stimulation results in the release of pro
      inflammatory mediators. These mediators cause bone resorption and deposition at
      the pressure and tension sites and play a role in OTM. Thus, assessment of
      chemical biomarkers can help determine the exact amount of load and its duration
      of application required for each tooth and select the most efficient treatment
      plan with minimal complications. Objective: This study aimed to determine the
      level of tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) in
      gingival crevicular fluid (GCF) during OTM. Methods: This randomized split-mouth
      clinical trial (parallel) was performed on 10 patients who were presenting to the
      Orthodontic Department of Qazvin University of Medical Sciences from November
      2015 to June 2016. A canine tooth was randomly selected as the study group and
      subjected to distalization force while the contralateral canine tooth served as
      control. Using paper strip, GCF was collected from the study and control teeth
      prior to orthodontic force application (T0), one hour after (T1) and 28 days
      after force application (T2), then the level of TNFalpha and IL-6 was measured
      using ELISA. Data were analyzed using SPSS version 20 via Friedman and Wilcoxon
      test, and considering the significance level at p<0.05. Results: The level of
      TNFalpha (p=0.0799) and IL-6 (p=0.678) at both sides of study teeth was higher
      than both side of control teeth at T1. Also, the level of IL-6 (p=0.515) and
      TNFalpha (p=0.508) were higher at the tension side compared to the pressure side;
      but the difference was not statistically significant. Conclusion: Due to the free
      circulation of GCF in gingival sulcus, the level of mediators in the GCF
      collected from the mesial and distal areas alone cannot serve as a suitable index
      for assessment of activity at the tension and pressure sites. Trial registration:
      The trial was registered at the Iranian Registry of Clinical Trials with the IRCT
      ID: IRCT2017030632903N2. Funding: The present study was supported by a grant from
      the Research Council, Qazvin University of Medical Sciences, Qazvin, Iran (thesis
      no.: 40).

PMID- 30214697
TI  - Effect of self-acupressure on fasting blood sugar (FBS) and insulin level in type
      2 diabetes patients: a randomized clinical trial.
AB  - Background: Uncontrolled symptoms of diabetes can lead to irreparable damage to
      vital organs. Despite the global trend towards the use of complementary
      alternative therapies, few studies have evaluated the effectiveness of self
      acupressure in diabetes patients. Objective: The aim of this study was to
      determine the effect of self-acupressure on FBS and insulin level in type 2
      diabetes patients. Methods: This randomized clinical trial was performed from
      September 2016 to February 2017. A total of 60 diabetic patients were selected
      from diabetes clinic in Rafsanjan in Iran, according to inclusion and exclusion
      criteria and then assigned to 2 groups (30 in acupressure and 30 in control)
      randomly by the minimization method. The intervention group received acupressure
      at ST-36, LIV-3, KD-3 and SP-6 points bilaterally for five minutes for each point
      in 10 seconds pressure and 2 seconds rest periods. Subjects in the control group
      received no intervention. The FBS and insulin levels were measured before and
      after the intervention for both groups. The data were analyzed by SPSS version 16
      by the Chi-square test, independent-samples t-test, and paired-samples t-test. A
      level of 0.05 was considered significant for examining the hypotheses. Results:
      There were no significant differences between the acupressure and control group
      regarding age, sex and level of education. The insulin level significantly
      increased after treatment in the acupressure group (p=0.001). There were no
      significant differences between the levels of insulin in study or control groups.
      Serum FBS level decreased significantly after intervention in the acupressure
      group compared to the control group (p=0.02). Conclusion: Self-acupressure as a
      complementary alternative medicine can be a helpful complementary method in
      reducing FBS and increasing insulin levels in type 2 diabetic patients. Trial
      registration: This trial was registered at the Iranian Registry of Clinical
      Trials with clinical trial registration number: IRCT2016122131459N1. Funding:
      This study was financially sported by Deputy of Research and Technology of
      Rafsanjan University of Medical Sciences (Ref: 20.519).

PMID- 30214698
TI  - The risk of cardiovascular events based on the Framingham criteria in Adults
      Living in Mashhad (Iran).
AB  - Background and aim: Cardiovascular diseases are a problem in low- and middle
      income countries, such as Iran. The present research was performed to identify
      risk factors contributing to cardiovascular diseases and their distributions
      among the adult population of Mashhad (Iran) using the Framingham criteria.
      Methods: This cross-sectional population-based study performed in 2015 on 2,976
      adults living in Mashhad (Iran) using Stratified cluster-random sampling method.
      Demographic information was acquired by surveyors in the research team using a
      checklist and referring to a medical laboratory for laboratory assessments. The
      10-year risk of cardiovascular diseases for the participants was calculated using
      the Framingham criteria and was classified into three classes: low risk (<10%),
      intermediate risk (10-20%), and high risk (>20%). The analysis was done by SPSS
      Version 11.5 by using the Independent-samples t-test, Kruskal-Wallis, and
      analysis of variance (ANOVA). Results: A total of 2,978 participants aged 16-90
      participated in our cross-sectional study with an average age of 43.5+/-14.7
      years. Total risk scores among men and women were 7.29+/-6.3 and 5.8+/-6.03,
      respectively. Compared to women, men exhibited a significantly higher risk of
      cardiovascular diseases (p<0.001). Average heart age among men and women was
      estimated at 50.37+/-18.7 and 48.8+/-17.0 respectively, i.e. significantly older
      heart age was obtained for men compared to women (p<0.001). Conclusion: According
      to this study, men are at a great risk of cardiovascular events, so we should
      develop our screening and educational program especially for this population.

PMID- 30214699
TI  - Thyrotoxic periodic paralysis: case report and review of the literature.
AB  - Introduction: Thyrotoxic periodic paralysis (TPP) is a rare and potentially
      lethal complication of hyperthyroidism. It is characterized by sudden onset
      paralysis associated with hypokalemia. Management includes prompt normalization
      of potassium, which results in resolution of the paralysis. Definitive treatment
      of hyperthyroidism resolves TPP completely. Case presentation: A 23-year-old
      African American male patient presented to the emergency room at the University
      of Mississippi Medical Center, USA in November 2016 with sudden onset
      quadriplegia. He also endorsed a history of weight loss, palpitations, heat
      intolerance and tremors. The patient reported similar episodes of quadriplegia in
      the past, which were associated with hypokalemia and resolved with normalization
      of potassium levels. Physical examination was significant for exophthalmos,
      smooth goiter with bruit consistent with the diagnosis of Graves' disease.
      Laboratory assessment showed severe hypokalemia, hypomagnesemia, suppressed
      thyroid stimulating hormone (TSH) and high free thyroxine (T4). Urine potassium
      creatinine ratio was less than one, indicating transcellular shift as the cause
      of hypokalemia. After normalization of potassium and magnesium, the paralysis
      resolved in 12 hours. He was started on methimazole. On follow up, the patient
      was clinically and biochemically euthyroid with no further episodes of paralysis.
      Take-away lesson: TPP is a rare and reversible cause of paralysis. Physicians
      need to be aware of the diagnostic and treatment modalities as delayed
      recognition in treatment could result in potential harm or unnecessary
      interventions.

PMID- 30214700
TI  - Tumefactive multiple sclerosis masquerade as a central nervous system tumor: a
      case report.
AB  - Introduction: Tumefactive multiple sclerosis is a demyelinating disorder that
      appears tumor-like on MRI. To most physicians, diagnosing tumefactive MS by
      applying clinical, radiological, or laboratory examination like Cerebrospinal
      fluid (CSF) analysis, can be challenging and ultimately biopsy is necessary to
      confirm the diagnosis. Case presentation: This paper reports a case of a 37-year
      old woman who presented with progressive headache and a strong family history of
      cancer and was misdiagnosed as having a CNS glioma. After considering the MRI
      features, CSF analysis results and observing improvement with IV steroids, the
      diagnosis of tumefactive MS was made. The patient refused biopsy to rule out the
      possibility of tumor or abscess. Nine months later, she presented with another
      relapse and an injectable disease modifying treatment (DMT) was initiated, and
      her course has been stable in follow up. Take-away lesson: The overall clinical
      importance of this case report is to highlight the real possibility of being
      forced to decide between Tumefactive demyelinating lesions (TDLs) and brain
      tumors in clinical practice, in order to avoid unnecessary biopsy.

PMID- 30214701
TI  - Validation of the Family Stability Questionnaire in married couples: a
      confirmatory factor analysis.
AB  - Background: Marital conflicts and divorce are among the most crucial problems of
      society. Therefore, it is important to maintain family stability at the optimal
      level in order to prevent divorce and its consequences in the family and
      community. Objective: This study was conducted to design and validate the Family
      Stability Questionnaire (FSQ) in married couples. Methods: This study was the
      second stage of a large study. The FSQ was constructed based on a qualitative
      research in our previous study in 2016. It was developed through interviews by
      family therapists, psychiatrists, and couples on 10 dimensions (areas) and was
      based on McMaster's Family Assessment Device (FAD). Then, in the present study, a
      confirmatory factor analysis was conducted on 270 males and females (135 couples)
      of Yazd City (Iran) from January to May 2017. The construct validity and
      reliability of the scales were examined using exploratory and confirmatory factor
      analyses (EFA and CFA) and Cronbach's alpha coefficient, respectively. Test
      retest reliability was assessed with intra-class correlation coefficients (ICC)
      for the agreement between the individual items and domains. SPSS 21 and AMOS 21
      were used for statistical analyses (p<=0.05). Results: At first, the results of
      the CFA on 70 items of FSQ could not confirm (RMSEA=0.06, CFI=0.91, GFI=0.72),
      but FSQ with 56 questions indicated that it had sufficiently high validity and
      reliability to measure family stability (RMSEA=0.04, CFI=0.95, GFI=0.96) with an
      acceptable fit index. A positive significant correlation was observed between the
      FSQ and FAD (r=0.45, p<0.001) indicating that FSQ has convergent validity. The
      Cronbach's alpha and ICC of more than 0.7 in 10 domains of this tool indicated a
      good internal consistency among the items and their high relevance (0.90 and
      0.84, respectively). Conclusion: FSQ, as a multi-dimensional questionnaire, is a
      useful and reliable instrument to assess family stability. It consists of ten
      factors, which were constructed for the first time in Iran. Given the proper
      features, this instrument can be utilized to carry out more research regarding
      family stability in Iranian populations.

PMID- 30214702
TI  - Evaluation of computerized provider order entry systems: assessing the usability
      of systems for electronic prescription.
AB  - Background: The field of medicine has been influenced by the growth and
      development of information systems such as the Computerized Provider Order Entry
      (CPOE) System. Objective: This study aimed to evaluate the usability of CPOE
      systems for electronic prescription in Tehran, Iran. Methods: This was an
      evaluation study conducted in 2017. The research population consisted of the CPOE
      systems used in hospitals of Tehran (Iran) and nurses who had access to, and
      used, the CPOE systems. Five hospitals with CPOE systems were included in the
      research sample. The data were collected using a questionnaire, and included a
      total of 50 questions. The questionnaires were distributed among 254 nurses who
      were the users of the systems. Data analysis was performed by IBM-SPSS version
      21, using independent-samples t-test. A p-value of <=0.05 was considered
      statistically significant. Results: Among the four aspects assessed, the "user
      friendliness" (3.87+/-0.59) had the highest mean score. The lowest mean score
      (2.01+/-0.58) was related to the "decision support" feature of the systems. The
      highest and lowest mean scores for "prescription support" criterion belonged to
      system E (3.26+/-0.23) and system C (1.90+/-0.16), respectively. There was a
      statistically significant difference between the usability of the systems used in
      the private and the public hospitals (p<0.001). It was found that the CPOE
      systems in private hospitals had a higher level of usability (3.42+0.10) compared
      to those in public hospitals (2.91+0.25). Conclusion: Two main functions of the
      studied CPOE systems i.e., decision support and prescription support should be
      developed to make electronic prescription safer and more intuitive. Addressing
      usability aspects of CPOE systems in practice could improve the usability of
      these systems for prescription.

PMID- 30214703
TI  - Explaining nurses' experiences of caring for brain dead patients: a content
      analysis.
AB  - Background: Caring for patients with brain death diagnosis is the heaviest of
      duties for nurses, and, due to the complexities and stressors, it is the biggest
      challenge of nursing in an intensive care unit. Objective: This qualitative
      research aimed to disclose the nurses' experience of caring for brain-dead
      patients. Methods: The present study was a qualitative research using a content
      analysis, where the data collection process included 21 semi-structured and in
      depth interviews with intensive care nurses, physicians, head nurses, a
      transplantation committee coordinator, and the authority of the organ procurement
      unit. Adequate data were collected from March 2014 until the saturation point was
      reached in June 2016. Data were analyzed simultaneously with data collection
      using qualitative content analysis with a conventional approach. Results:
      Qualitative content analysis of data resulted in two themes and eight subthemes,
      reflecting the analysis of nurses' experiences of caring for brain-dead patients.
      The themes included "Challenges of right and duty requirement," and "turbulent
      confrontation with successive chains of tension". Finally, the main themes of
      "resonance of stress and internal conflict in care" were abstracted. Conclusion:
      The findings deepened our understanding and knowledge of the issue. Despite all
      the stress, nurses care for potential organ donors, and this results in
      preserving the organs' viability for donation. Nurses' problems and challenges in
      this caring process should be considered by policymakers of health and treatment
      systems and a supportive model be designed for nurses in the intensive care unit.

PMID- 30214704
TI  - Prevalence of seasonal influenza vaccination among primary healthcare workers in
      Arar city, Saudi Arabia.
AB  - Background: Influenza outbreaks occur annually and have significant ramifications
      on the wellbeing of the population. Influenza is given high priority in Saudi
      Arabia where numerous reports of different types of influenza outbreaks have
      occurred in recent years. Objective: The study aimed to determine the prevalence
      of influenza vaccination among healthcare providers. Methods: The study employed
      a cross-sectional design, and data was collected using a predesigned
      questionnaire which was validated by a panel of experts and tested for
      reliability (Cronbach's alpha =0.8). All primary healthcare workers in Arar city
      (Saudi Arabia) were taken as a comprehensive sample between January and March
      2018. The questionnaire used a Likert scale that assessed the reasons for
      embracing or rejecting the influenza vaccines. A p-value of <=0.05 was considered
      statistically significant. Results: In total, 204 health professionals (72
      physicians, 102 nurses and 30 other staff members) filled the questionnaire. The
      mean age of the healthcare professionals was 31.9+/-8.7 years. Self-report of
      seasonal influenza vaccination uptake was 55.9% (65.3% for physicians, 55.9% for
      nurses and 33.3% for other staff). Perceived risk of severity of influenza was
      2.5 times more in the compliant group than that of the non-compliant group
      (p<0.001, 95% CI: 1.4-4.4). Conclusion: Utilization of influenza vaccine is 55%
      in both nurses and physicians despite 89% of them being aware of influenza
      vaccination guidelines and MOH recommendations. It is needed to ensure the
      intensive education of healthcare providers to understand the protective value of
      influenza vaccine.

PMID- 30214705
TI  - Prevalence and psychological impact of Acne vulgaris among female secondary
      school students in Arar city, Saudi Arabia, in 2018.
AB  - Background: Acne vulgaris is a common heath problem affecting adolescents with
      considerable impact on their quality of life. Objective: To determine the
      prevalence of Acne vulgaris and its psychological impact among female secondary
      school students. Methods: A cross-sectional study was conducted during the period
      from January to March 2018, among all female secondary school students in 3
      randomly selected schools, in Arar city (Saudi Arabia). The participants were
      clinically examined by a dermatologist to identify acne cases. Dermatological
      quality of life of acne cases were assessed using an Arabic version of
      Dermatology Life Quality Index (DLQI). Data collected were analyzed by IBM-SPSS
      version 20, using Chi-square, Fisher's Exact test, Mann-Whitney U, and Kruskal
      Wallis test. P-value <=0.05 was considered statically significant. Results: The
      overall prevalence of Acne vulgaris was 14.3%. It was not significantly affected
      by age, marital status or nationality of participants. Post inflammatory hyper
      pigmentation and scarring were detected in 11.6% and 8.7% respectively. Twenty
      nine percent of the cases had no impact; 56.3% had small to moderate impact and
      14.5% had large effect. The psychological impact was significantly increased with
      increased severity, presence of acne lesions on face and other sites, presence of
      hyper pigmentation and scarring (p=0.001). Conclusion: Acne vulgaris had large
      impact on quality of life in 14.5% of cases. Students should be counseled and
      educated on how to deal with this dermatological problem.

PMID- 30214706
TI  - Supero-medial reduction mammaplasty: a safe and reliable technique in
      gigantomastia and severe breast ptosis.
AB  - Reduction mammaplasty in huge breasts poses a great challenge for plastic
      surgeons. The classic technique is free nipple and areola grafting after breast
      amputation. This paper is a short technical report of reduction mammoplasty on 40
      patients with severe breast ptosis (suprasternal notch to nipple >35 cm) and
      giganticomastia (anticipated resection of more than 1 kg per breast) were
      operated upon using superomedial pedicle technique for reduction mammaplasty. All
      patients were satisfied with their results aesthetically, and showed relief in
      their neck pain. There were no cases of total nipple-areola loss. In one breast,
      the nipple-areolar complex (NAC) was congested intra-operatively and free nipple
      grafting was done. The NAC sensation was preserved in 36 cases, and all other
      complications were minimal and self-limiting. The superomedial pedicle technique
      has proven to be a safe and reliable method for reduction mammaplasty in huge
      breasts. Compared to the classic free nipple and areola technique, this method
      showed promising results in preserving the nipple sensation and giving more
      pleasant natural projecting breasts.

PMID- 30214707
TI  - Engagement and availability in shaping nurses' management of postoperative pain:
      a qualitative study.
AB  - Background: Studies reporting inadequate nursing care for patients indicate that
      nurses are negatively affected in such situations, and research is needed to
      study nursing care in postoperative situations. Objective: To describe situations
      of postoperative pain management in a surgical ward in Thailand. Methods: A
      qualitative approach using the Critical Incident Technique was chosen to
      investigate situations of postoperative pain management from the perspective of
      surgical nurses in Thailand. Data were collected through multiple semi-structured
      interviews with nine nurses over a five-week period. Results: The situations of
      surgical nurses described three elements that heavily influenced the quality of
      postoperative pain management: engagement in a trustful nurse-patient
      relationship, availability of pain medication and nursing care when needed, and
      imbalance between meeting the patient's needs and completing routine nursing
      duties. Conclusion: The results help to expand our understanding of how Thai
      nurses manage pain in postoperative situations and indicate areas that could be
      improved in terms of how nurses respond to patients' pain. Nurses challenge
      existing guidelines and facilitate development of new nursing guidelines and/or
      policies in pain management.

PMID- 30214708
TI  - The effects of mobile text messages on raising knowledge of men with type 2
      diabetes, Isfahan, 2015: an educational experimental study.
AB  - Background: Diabetes is one of the most common metabolic disorders which are
      rapidly increasing. Distance training is a cost-effective, easy and accessible
      way in which time and place dimensions of communication are removed. Objective:
      To determine the effects of mobile text messages on raising knowledge of men with
      type 2 diabetes. Methods: This educational experiment recruited 76 people
      selected by convenient sampling from a population of male patients with type 2
      diabetes presenting to Sedigheh Tahereh Research Center in Isfahan, Iran, in
      2015. They were randomly assigned into intervention and control groups. Data were
      collected with a questionnaire of demographic characteristics and questions
      pertaining to the variable of knowledge, through interview. The intervention
      group received training and follow-up through cell phones and text messages for
      12 weeks. Data were analyzed in IBM-SPSS version 20 using Mann-Whitney test, Chi
      square, Independent-samples t-test and paired-samples t-test. Results: Findings
      suggested that patients' knowledge in both groups significantly increased after
      the training (p<0.001). However, this rise in the intervention group was
      significantly higher than that of the control group (p<0.001). Conclusion: The
      results indicated that designing and implementing educational programs based on
      text messages and cell phones can improve knowledge in diabetics.

PMID- 30214709
TI  - Housing and Service Interventions for Families Experiencing Homelessness in the
      United States: An Experimental Evaluation.
AB  - This paper examines the housing and service interventions that work best to end
      family homelessness and to promote housing stability, adult and child well-being,
      family and self-sufficiency in the United States. It is based on the short-term
      (20-month) results of the Family Options Study, which recruited 2,282 families in
      emergency homeless shelters across 12 sites and randomized them to one of three
      housing and service interventions or to usual care in their communities. The
      approaches test both theoretical propositions about the nature of family
      homelessness and practical efforts to end it. Permanent housing subsidies were
      most successful at ending homelessness and promoting housing stability and had
      radiating impacts on all the other domains, suggesting that homelessness among
      families in the United States is centrally a problem of housing affordability.
      Project-based transitional housing, which attempts to address families'
      psychosocial needs in supervised settings, and temporary 'rapid re-housing'
      subsidies had little effect.

PMID- 30214710
TI  - A challenging abdomino-scrotal hydrocele-successful resolution with the help of
      interventional radiology guided sclerosis.
AB  - Abdomino-scrotal hydrocele is a rare condition that presents in male infants.
      There is no consensus in the literature over treatment. We present the case of a
      4-year-old boy with what was thought to be a straight forward congenital
      hydrocele that persisted despite ligation of a patent processus vaginalis and a
      Jaboulay procedure. A subsequent Magnetic Resonance Imaging scan identified a
      large intra-abdominal component connecting to the scrotum. Laparoscopic excision
      of the intra-abdominal component was performed successfully, but the hydrocele
      persisted. The hydrocele resolved without complication following two episodes of
      image intensifier guided sclerotherapy carried out by the interventional
      radiology team.

PMID- 30214711
TI  - Spontaneous reduction of acute cecal herniation through the foramen of Winslow.
AB  - This is the case of a 70-year-old woman who presented to the emergency department
      complaining of 2 hours of acute-onset epigastric pain. She had experienced this
      pain once before which had spontaneously resolved. Axial imaging demonstrated the
      cecum in an abnormal position within the lesser sac, as well as compression of
      the inferior vena cava and portal vein. She was taken emergently to the operating
      room for laparotomy, where a free-floating cecum and ascending colon was
      identified without ischemia, and a right hemicolectomy was performed. Foramen of
      Winslow hernias are rare internal hernias with a high rate of strangulation and
      bowel ischemia, requiring urgent surgical intervention. Operative treatment
      depends on the type of herniated viscera. Spontaneous reduction is not well
      documented.

PMID- 30214712
TI  - The rare and unusual presentation of a gastric perforation in the setting of a
      large diaphragmatic hernia: a case report and literature review.
AB  - Diaphragmatic hernias are either congenital or acquired defects in the diaphragm
      that permit passing of abdominal contents into the chest cavity. Individuals with
      large diaphragmatic hernias associated with a gastric perforation have rarely
      been reported in literature and can have serious mortality rates. Herein, we
      present a case of gastric perforation in the setting of a significant sized
      diaphragmatic hernia. The value of the current report compared to previously
      published cases is the sub-acute nature and lack of any indicative features on
      initial presentation which can lead to misdiagnosis and serious morbidity later
      in life.

PMID- 30214713
TI  - Cecal volvulus caused by internal herniation after roux-en-y gastric bypass
      surgery.
AB  - Cecal volvulus is the rotation of a mobile cecum resulting in a large bowel
      obstruction. We present the case of a 55-year-old female who underwent a roux-en
      y gastric bypass in 2003 and presented to the emergency department with worsening
      abdominal pain, distention and obstipation. Roentgenogram demonstrated a 14 cm
      colon suggestive of sigmoid volvulus, but CT scan showed rectal contrast abruptly
      ending in the distal transverse colon, mesenteric swirling and a distended cecum,
      consistent with cecal, rather than sigmoid, volvulus. Upon surgical exploration
      the majority of the small bowel, cecum and ascending colon had herniated through
      the transverse mesocolon defect created during her prior gastric bypass. The
      bowel was reduced through the mesenteric defect, and an ileocecectomy was
      performed. This is, to our knowledge, the first reported case of cecal volvulus
      caused by an internal hernia through a mesocolon defect created during a prior
      roux-en-y gastric bypass operation.

PMID- 30214714
TI  - Calu-3 epithelial cells exhibit different immune and epithelial barrier responses
      from freshly isolated primary nasal epithelial cells in vitro.
AB  - Epithelial cell lines are often used to evaluate the effect of
      exogenous/endogenous stimuli on epithelial barrier function and innate immune
      responses in allergic airway diseases, without clear view on differences between
      epithelial cell lines and primary nasal epithelial cell responses. In this
      observational study, we compared the response of Calu-3 and primary nasal
      epithelial cells to two relevant exogenous stimuli: i.e. Staphylococcus aureus
      enterotoxin B (SEB) and house dust mite (HDM). Stimulation of Calu-3 cells with
      SEB decreased epithelial integrity in a dose dependent manner, which was
      associated with a significant increase in IL-6 and IL-8 production. In contrast,
      no alteration in barrier integrity or IL-6 and IL-8 production was seen when
      primary nasal epithelial cells were stimulated with SEB. HDM extract altered the
      integrity of primary nasal epithelial cells, but not of Calu-3 epithelial cells.
      Increased IL-8 production was seen after stimulation with HDM in primary nasal
      epithelial cells and not in Calu-3 epithelial cells. In conclusion, immune and
      barrier function differ between different epithelial cell types studied. As a
      consequence, care must be taken when interpreting data using different epithelial
      cell types.

PMID- 30214715
TI  - Impact of the workforce distribution on the viability of the osteopathic
      profession in Australia: results from a national survey of registered osteopaths.
AB  - Background: Workforce distribution has an important influence on the quality of
      healthcare delivered in a region, primarily because it impacts access to health
      services in the community and overall health equity in the population.
      Distribution of osteopaths in Australia does not appear to follow the Australian
      population with the majority of osteopaths located in Victoria. The implications
      of this imbalance on the osteopathic workforce have not yet been explored.
      Methods: A secondary analysis of data from a survey of 1531 members of Osteopathy
      Australia in 2013. The analysis focused on the practice and occupational
      characteristics associated with practice locality. Results: The survey was
      completed by a representative sample of 432 osteopaths. Respondents practicing
      outside Victoria were more likely to report higher income across all income
      brackets, and were less likely to report a preference for more patients.
      Conclusions: The Australian osteopathic profession should examine the issue of
      imbalanced workforce distribution as a priority. The results of this study are
      worth considering for all stakeholders as part of a coordinated approach to
      ensure the ongoing health of the Australian osteopathic workforce.

PMID- 30214716
TI  - Nuptial gift chemistry reveals convergent evolution correlated with antagonism in
      mating systems of harvestmen (Arachnida, Opiliones).
AB  - Nuptial gifts are material donations given from male to female before or during
      copulation and are subject to sexual selection in a wide variety of taxa. The
      harvestman genus Leiobunum has emerged as a model system for understanding the
      evolution of reproductive morphology and behavior, as transitions between
      solicitous and antagonistic modes of courtship have occurred multiple times
      within the lineage and are correlated with convergence in genital morphology. We
      analyzed the free amino acid content of nuptial gift secretions from five species
      of Leiobunum using gas chromatography-mass spectrometry. Multivariate analysis of
      the free amino acid profiles revealed that, rather than clustering based on
      phylogenetic relationships, nuptial gift chemical composition was better
      predicted by genital morphology and behavior, suggesting that convergent
      evolution has acted on the chemical composition of the nuptial gift. In addition,
      we found that, species with solicitous courtship produce gifts consisting of a
      19% larger proportion of essential amino acids as compared to those with more
      antagonistic courtship interactions. This work represents the first comparative
      study of nuptial gift chemistry within a phylogenetic framework in any animal
      group and as such contributes to our understanding of the evolution of
      reproductive diversity and the participant role of nuptial gift chemistry in
      mating system transitions.

PMID- 30214717
TI  - Synthesis of water-degradable silica nanoparticles from carbamate-containing
      bridged silsesquioxane precursor.
AB  - Silica nanoparticles (SNPs) are attractive for applications for the delivery of
      drugs and as imaging agents due to their ease of synthesis and scale up, robust
      structure, and controllable size and composition. Degradability is one important
      factor that limits biomedical applications of SNPs. With this in mind, we
      designed, prepared and characterized novel hydrolysable organosilica
      nanoparticles (ICPTES-Sorbitol SNPs). These particles were prepared by co
      condensation of tetraethoxysilane with a bridged sorbitol-based silsesquioxane
      precursor containing carbamate linkages. The non-porous spherical ICPTES-Sorbitol
      SNPs became porous after they were placed in an aqueous environment as a result
      of the hydrolysis of carbamate bonds and were completely degraded upon prolonged
      exposure to water. The rate of degradation depended on the pH of the solution,
      with nanoparticles degrading slower at pH 2 than at pH 4 or pH 7. The degradation
      was demonstrated by transmission electron microscopy, nitrogen desorption
      analysis and solution analytical techniques such as ICP-MS and molybdenum blue
      assay, which was also used to follow the dissolution of ICPTES-Sorbitol SNPs.

PMID- 30214718
TI  - The effect of antibiotic stewardship interventions with stakeholder involvement
      in hospital settings: a multicentre, cluster randomized controlled intervention
      study.
AB  - Background: There is limited evidence from multicenter, randomized controlled
      studies to inform planning and implementation of antibiotic stewardship
      interventions in hospitals. Methods: A cluster randomized, controlled,
      intervention study was performed in selected specialities (infectious diseases,
      pulmonary medicine and gastroenterology) at three emergency care hospitals in
      Western Norway. Interventions applied were audit with feedback and academic
      detailing. Implementation strategies included co-design of interventions with
      stakeholders in local intervention teams and prescribers setting local targets
      for change in antibiotic prescribing behaviour. Primary outcome measures were
      adherence to national guidelines, use of broad-spectrum antibiotics and change in
      locally defined targets of change in prescribing behaviour. Secondary outcome
      measures were length of stay, 30-day readmission, in-hospital- and 30-day
      mortality. Results: One thousand eight hundred two patients receiving antibiotic
      treatment were included. Adherence to guidelines had an absolute increase from 60
      to 66% for all intervention wards (p = 0.04). Effects differed across specialties
      and pulmonary intervention wards achieved a 14% absolute increase in adherence (p
      = 0.003), while no change was observed for other specialties. A pulmonary ward
      targeting increased use of penicillin G 2 mill IU * 4 for pneumonia and COPD
      exacerbations had an intended increase of 30% for this prescribing behaviour (p <
      0.001). Conclusions: Pulmonary wards had a higher increase in adherence,
      independent of applied intervention. The effect of antibiotic stewardship
      interventions is dependent on how and in which context they are implemented.
      Additional effects of interventions are seen when stakeholders discuss ward
      prescribing behaviour and agree on specific targets for changes in prescribing
      practice.

PMID- 30214719
TI  - Resistance pattern and maternal knowledge, attitude and practices of suspected
      Diarrheagenic Escherichia coli among children under 5 years of age in Addis
      Ababa, Ethiopia: cross sectional study.
AB  - Background: Diarrheal illness remains one of the leading causes of morbidity and
      mortality among children under 5 years of age worldwide, especially in developing
      countries. Diarrheagenic Escherichia coli (DEC) is the major cause of
      gastroenteritis in children in the developing world and is associated with high
      resistance levels to antibiotics. The aims of this study were to isolate and
      determine susceptibility patterns of DEC among children under 5 years of age with
      acute diarrhea and to assess maternal knowledge, attitude and practice towards
      childhood diarrhea. Methods: A cross sectional study was conducted from August
      December 2015 at 3 selected health institutions. Stool samples were cultured and
      isolated E. coli species were run for antimicrobial susceptibility testing using
      disk diffusion method. In addition, children's caretakers were interviewed using
      structured questionnaires including a Knowledge, Attitude and Practice (KAPs)
      survey. Bivariate and multivariate logistic regression analysis was used to
      quantify the effect of different risk factors on bacterial related diarrhea.
      Results: A total of 253 children, 115 males and 138 females with acute diarrhea
      were enrolled. E. coli was identified in a total of sixty-one children (24.1%),
      followed by Shigella (9.1%) and Salmonella (3.95%). Additionally, eighty-six
      children (34.0%) had parasites identified in stool samples. E. coli isolates
      showed 83.6% resistance to ampicillin and augmentin followed by, trimethoprim
      sulfamethoxazole (62.3%). Multiple resistances were observed in 72.1% of
      isolates; however, more than 90% of the strains were sensitive to ciprofloxacin
      and ceftriaxone. Caretakers identified the following as causes of infection:
      contaminated food and water (83.4%), microorganisms (55.3%), inadequate breast
      milk (54.1%), teething (45.1%), house flies (43.1%) and evil eye (15.8%). No hand
      washing before meals and low levels of knowledge had a significant association
      with E. coli infection (p < 0.05). Conclusion: In children with suspected
      diarrheagenic E. coli, we observed a high frequency of multidrug resistant E.
      coli. Furthermore, study subjects with low awareness about source, cause and
      symptoms of the disease were more likely to acquire suspected diarrheagenic E.
      coli infections. Thus, there is a need for more education in addition to
      continuous surveillance of the prevalence and antibiotic susceptibility pattern
      of diarrheal bacterial isolates in hospitals and in the community.

PMID- 30214722
TI  - Self-check with plaque disclosing solution improves oral hygiene in
      schoolchildren living in a children's home.
AB  - Background: The effectiveness of an oral hygiene program for children living in a
      children's home has been reported. However, to the best of our knowledge, no
      studies have evaluated the possible effects of self-checking of oral health among
      children residing in a children's home. The objective of this study was to
      examine if self-checking using plaque disclosing solution improves oral hygiene
      in schoolchildren living in a children's home. Methods: We enrolled nine
      schoolchildren (six girls) without untreated decayed teeth living in a children's
      home in Japan. This preliminary study was designed as a 5-month program
      comprising group and individual instructions and self-checking using plaque
      disclosing solution. Paired t-test and Wilcoxon signed-rank test were used for
      statistical analysis to evaluate the change of Plaque Control Record (PCR) and
      Patient Hygiene Performance (PHP). Results: The mean PCR significantly decreased
      to 38.7% after 3 months of self-checking using disclosing solution compared with
      that before self-checking (i.e., at 1 month) (60.7%) (P < 0.01). PHP score
      significantly decreased to 1.4 at 4 months compared with that at baseline (2.8)
      and at 1 month (2.7) (P = 0.012 and P = 0.018). Improvement of oral hygiene
      status was evaluated according to the ratio of PCR at 4 months to that at 1
      month. The average improvement ratio was 0.4 +/- 0.35 (range: 0.0-1.0).
      Significant correlation was not found between improvement rate and school grade
      (r = 0.63, P = 0.070). Conclusions: Our results suggest that self-checking with
      disclosing solution may be effective in improving oral hygiene among
      schoolchildren at a children's home.

PMID- 30214723
TI  - An uncommon cause of hemoptysis: aortobronchial fistula.
AB  - Background: Hemoptysis is a frequent sign of respiratory and non-respiratory
      diseases. While in most cases the underlying cause is rapidly identified,
      sometimes the real etiology might be misdiagnosed with dramatic delay in
      treatment. Case presentation: A 46-year-old man with hiatal hernia and a history
      of aortic surgery for aortic coarctation presented with dramatic episodes of
      hemoptysis and subsequent severe anemia (6,9 g/dl). Digestive and respiratory
      endoscopy resulted not exhaustive, thus he underwent a contrast-enhanced computed
      tomography (CT) scan of the chest that showed an aneurysmal dilatation of the
      descending thoracic aorta with suspected aortobronchial fistula. He underwent
      cardiac surgery that confirmed the diagnosis and successfully treated the
      fistula. Conclusion: We briefly review the literature to raise clinical awareness
      on this uncommon cause of hemoptysis.

PMID- 30214721
TI  - Determining the IgG concentrations in bovine colostrum and calf sera with a novel
      enzymatic assay.
AB  - Background: Immune protection in newborn calves relies on a combination of the
      timing, volume and quality of colostrum consumed by the calf after birth. Poor
      quality colostrum with inadequate immunoglobulin concentration contributes to
      failed transfer of passive immunity in calves, leading to higher calf morbidity
      and mortality. Therefore, estimating colostrum quality and ensuring the transfer
      of passive immunity on farm is of critical importance. Currently, there are no on
      farm tools that directly measure immunoglobulin content in colostrum or serum.
      The aim of this study was to apply a novel molecular assay, split trehalase
      immunoglobulin G assay (STIGA), to directly estimate immunoglobulin content in
      dairy and beef colostrum and calf sera, and to examine its potential to be
      developed as on-farm test. The STIGA is based on a split version of trehalase
      TreA, an enzyme that converts trehalose into glucose, enabling the use of a
      common glucometer for signal detection. In a first study, 60 dairy and 64 beef
      colostrum and 83 dairy and 84 beef calf sera samples were tested with STIGA, and
      the resulting glucose production was measured and compared with radial
      immunodiffusion, the standard method for measuring immunoglobulin concentrations.
      Results: Pearson correlation coefficients between the methods were determined and
      the sensitivity, specificity, and accuracy of the test were calculated for
      different colostrum quality and failed transfer of passive immunity cut-off
      points. The correlations of the STIGA measured by colorimetric enzymatic reaction
      compared to radial immunodiffusion for dairy and beef colostrum were 0.72 and
      0.73, respectively, whereas the correlations for dairy and beef sera were 0.9 and
      0.85, respectively. Next, STIGA was tested in a blinded study with fresh
      colostrum and serum samples where the correlation coefficient was 0.93 and 0.94,
      respectively. Furthermore, the performance of STIGA followed by glucometer
      readings resulted in correlations with radial immunodiffusion of 0.7 and 0.85 for
      dairy and beef colostrum and 0.94 and 0.83 for dairy and beef calf serum.
      Conclusions: A split TreA assay was validated for measurement of the
      immunoglobulin content of colostrum and calf sera using both a lab-based format
      and in a more user-friendly format compatible with on-farm testing.

PMID- 30214724
TI  - State of the art in tracheal surgery: a brief literature review.
AB  - Background: Tracheal surgery requires a highly specialized team of
      anesthesiologists, thoracic surgeons, and operative support staff. It remain a
      formidable challenge for surgeons due to the criticality connected to anatomical
      considerations, intraoperative airway management, technical complexity of
      reconstruction, and the potential postoperative morbidity and mortality. Main
      body: This article focuses on the main technical aspects and literature data
      regarding laryngotracheal and tracheal resection and reconstruction. Particular
      attention will be paied to anastomotic and non-anastomotic complications. Short
      conclusion: Results from literature confirm that, when feasible, laryngotracheal
      and tracheal resection and reconstruction is the treatment of choice in cases of
      benign stricture and malign neoplasm. Careful patient selection, operative
      planning, and execution are required for optimal results.

PMID- 30214720
TI  - Application of omics technologies for a deeper insight into quali-quantitative
      production traits in broiler chickens: A review.
AB  - The poultry industry is continuously facing substantial and different challenges
      such as the increasing cost of feed ingredients, the European Union's ban of
      antibiotic as growth promoters, the antimicrobial resistance and the high
      incidence of muscle myopathies and breast meat abnormalities. In the last decade,
      there has been an extraordinary development of many genomic techniques able to
      describe global variation of genes, proteins and metabolites expression level.
      Proper application of these cutting-edge omics technologies (mainly
      transcriptomics, proteomics and metabolomics) paves the possibility to understand
      much useful information about the biological processes and pathways behind
      different complex traits of chickens. The current review aimed to highlight some
      important knowledge achieved through the application of omics technologies and
      proteo-genomics data in the field of feed efficiency, nutrition, meat quality and
      disease resistance in broiler chickens.

PMID- 30214725
TI  - Usefulness of aspartate aminotransferase to platelet ratio index as a prognostic
      factor following hepatic resection for hepatocellular carcinoma.
AB  - Liver function is a major prognostic factor following hepatic resection for
      hepatocellular carcinoma (HCC), which is well correlated with the degree of
      fibrosis. On the other hand, the presence of liver cirrhosis itself leads to a
      higher incidence of HCC than chronic hepatitis. Therefore, preoperative
      noninvasive markers of fibrosis are important for the assessment of prognosis for
      treatment of HCC. The present study aimed to analyze whether aspartate
      aminotransferase to platelet ratio index (APRI) could predict prognosis following
      hepatic resection for HCC. The subjects were 162 patients who underwent hepatic
      resection for HCC between January 2000 and December 2011. The relationship
      between APRI and disease-free and overall survival were retrospectively
      investigated. In multivariate analysis, indocyanine green at 15 min (ICG-R15)
      >=15% (P=0.0306), APRI >=0.45 (P=0.0184), perioperative blood transfusion of red
      cell concentrates (RCC; P=0.0034) and TNM stage II, III or IV (P=0.0184) were
      significant predictors in disease-free survival. For overall survival, ICG-R15
      >=15% (P=0.0454), APRI >=0.45 (P=0.0417), perioperative blood transfusion of RCC
      (P=0.0036) and TNM stage II, III or IV (P=0.0033) were significant predictors. In
      addition, higher APRI values were positively correlated with hepatitis C virus
      infection and preoperative liver function. In conclusion, APRI is an independent
      risk factor for disease-free and overall survival following hepatic resection for
      HCC.

PMID- 30214726
TI  - Immunoexpression of claudins 4 and 7 among invasive breast carcinoma subtypes: A
      large diagnostic study using tissue microarray.
AB  - Molecular phenotyping and tissue microarray (TMA) studies have identified
      distinct invasive breast carcinoma subtypes: Luminal A, luminal B, enriched with
      overexpressed human epidermal growth factor receptor 2 (HER-2) and triple
      negative, i.e., negative for HER-2, as well as for estrogen and progesterone
      receptor (ER and PR, respectively) expression. These subtypes are useful in
      clinical management, since they bear distinct prognoses and predictive responses
      to targeted therapy. However, although molecular profiling provides important
      prognostic indicators, breast cancer risk stratification remains a challenge in
      triple-negative cases. What is referred to as claudin-low subtype was identified
      as a triple-negative subset that is associated with more aggressive tumor
      behavior and worse prognosis. However, the immunohistochemical expression of
      claudins has not yet been standardized. Our objective was to verify whether the
      immunoexpression of claudins 4 and 7 (the main claudins specifically expressed in
      human breast tissue) in TMA is associated with survival and prognosis in luminal
      A, HER-2 and triple-negative molecular subtypes. In this diagnostic study, we
      investigated ER/PR receptor status, HER-2, claudin 4 and 7 expression and stem
      cell CD44/24 profiles, and verified the association with prognosis and survival
      outcomes in 803 invasive breast carcinoma cases arranged in four TMAs. Among
      these, 503 (62.6%) were positive for claudin 4 and 369 (46.0%) for claudin 7.
      Claudin 4 exhibited the lowest expression in luminal A and triple-negative
      subtypes, and the highest frequency of expression in HER-2-enriched subtypes,
      whereas claudin 7 staining was not associated with any subtype. The stem cell
      phenotype was not associated with subgroups or claudins 4 and 7. Claudin
      immunoexpression profile was not able to distinguish between patients with better
      or worse prognosis, and it was not correlated to triple-negative cases.
      Therefore, it may be concluded that the immunoexpression of claudins 4 and 7,
      individually or within the usual immunohistochemical context (ER, PR and HER-2),
      does not provide additional prognostic information on breast cancer subtypes.

PMID- 30214727
TI  - Conversion surgery with gemcitabine plus nab-paclitaxel for locally advanced
      unresectable pancreatic cancer: A case report.
AB  - The standard treatment for locally advanced unresectable (UR-LA) pancreatic
      ductal adenocarcinoma (PDAC) is chemo-radiotherapy. Surgery following chemo
      radiotherapy (conversion surgery), has been considered a useful strategy and has
      been used for UR-LA PDAC. The current study presents the case of a 43-year-old
      woman who complained of back pain. A radiological examination revealed a
      pancreatic tumor in contact with >270 degrees of the superior mesenteric artery
      (SMA) perimeter, with invasion extending from the superior mesenteric vein (SMV)
      to the portal vein (PV). An endoscopic ultrasonography-guided fine needle
      aspiration biopsy revealed adenocarcinoma as the pathological diagnosis and the
      patient was diagnosed with UR-LA PDAC. Following 12 courses of combined
      gemcitabine plus nab-paclitaxel (GnP) for 9 months, the extent of tumor invasion
      to the SMA and SMV was improved and the level of cancer antigen (CA) 19-9
      decreased. A pancreatoduodenectomy with PV resection and reconstruction using a
      left renal vein graft were performed. Pathological examination revealed that the
      operative outcome was R0 (no residual tumor) resection and the patient was alive
      19 months after the initial treatment (9 months post surgery), however, there was
      local tumor recurrence. Between March 2015 and February 2016 a total of 10 cases
      of UR-LA PDAC were encountered at the Department of General Surgery, Chiba
      University Hospital (Chiba, Japan), in which GnP therapy was performed. Including
      the present case, 6 of the 11 cases (55%) underwent conversion surgery with
      curative resection. Kaplan-Meier analysis revealed that patients treated with
      conversion surgery presented significantly longer overall survival (OS) than
      those treated with no conversion surgery (median OS, 22.5 vs. 11 months; P=0.047,
      Wilcoxon test). The minimum reduction of CA19-9 was 67%. In conclusion,
      conversion surgery following GnP therapy is a desirable option for UR-LA PDAC. A
      significant reduction in the CA19-9 levels may be useful in determining the
      timing of changeover from medicine to surgery in patients with UR-LA PDAC in whom
      conversion surgery is being considered.

PMID- 30214728
TI  - Efficacy and safety of sunitinib in elderly patients with advanced renal cell
      carcinoma.
AB  - Elderly individuals represent a consistent proportion of all cancer patients.
      However, they are under-represented in clinical trials. The present study
      evaluated the actual tolerability of sunitinib in elderly Japanese patients with
      advanced renal cell carcinoma (RCC). A total of 56 consecutive patients with
      advanced RCC treated with sunitinib were enrolled. Patients were divided into two
      groups according to their age at the time of sunitinib initiation: i) elderly
      cohort (>=70 years); and ii) younger cohort (<70 years). Disease control rate,
      progression-free survival, overall survival and relative dose intensity (RDI)
      were compared between the two cohorts. The elderly cohort comprised of 14
      patients (25.0%), and the younger cohort included 42 patients (75.0%). The
      elderly cohort had a significantly higher Charlson comorbidity index than the
      younger cohort (mean, 9.7 vs. 7.9; P<0.0001). Disease control rate, progression
      free survival, and overall survival were not significantly different. The elderly
      cohort had a significantly lower RDI than the younger cohort (mean, 51.7 vs.
      65.0%; P=0.0340). Thus, treatment with sunitinib is feasible and effective in
      elderly Japanese patients with advanced RCC. However, the RDI of elderly patients
      was significantly lower, and a relatively low dose of sunitinib provided optimal
      therapeutic efficacy.

PMID- 30214729
TI  - Acute necrotizing pancreatitis as a fatal complication following DC Bead
      transcatheter arterial chemoembolization for hepatocellular carcinoma: A case
      report and review of the literature.
AB  - Transcatheter arterial chemoembolization (TACE) is one of the most effective
      palliative measures for patients with inoperable hepatocellular carcinoma (HCC).
      Acute pancreatitis is a rare but well-known complication following TACE. We
      herein present the case of a patient with HCC who developed fatal complications
      (acute necrotizing pancreatitis and upper gastrointestinal ulcers) after TACE
      with DC Beads. The patient was diagnosed with HCC in segments 4 and 8, measuring
      ~70 mm in greatest diameter, and he was treated by TACE. Hepatic arteriography
      revealed replacement of the origin of the right hepatic artery to the superior
      mesenteric artery, while the left hepatic artery originated from the celiac
      artery. After selection of the segmental arterial branches feeding the tumor, 2
      ml of 100-300-um-sized DC Beads loaded with 150 mg epirubicin were injected
      through the microcatheter. The patient complained of abdominal pain after the
      TACE procedure. Upper gastrointestinal endoscopy revealed longitudinal ulcers
      from the esophagus to the duodenum, and contrast-enhanced computed tomography
      revealed swelling of the pancreas and focal areas of low density in the
      pancreatic body, suggesting necrosis. The patient developed respiratory
      insufficiency, renal failure and sepsis, and finally succumbed to the
      complications 54 days after the procedure, despite general management of the
      acute pancreatitis. An autopsy revealed that the main cause of the patient's
      death was extensive pancreatic necrosis due to a gastroduodenal artery embolism
      after TACE with DC Beads. Therefore, it is crucial for treating physicians to be
      aware of this complication following TACE with DC Beads, particularly in patients
      with anatomical variations.

PMID- 30214730
TI  - Efficacy and safety of Nivolumab in non-small cell lung cancer patients in Tel
      Aviv tertiary medical center: Facing the reality.
AB  - Nivolumab is a human IgG4 programmed death (PD)-1 immune checkpoint inhibitor
      antibody, which is approved in Israel for the treatment of patients with advanced
      non-small cell lung cancer (NSCLC). It is also administered to individuals with
      disease progression during or after platinum-based chemotherapy, without a need
      to determine the level of PD-L1 expression in the tumor. The present study aimed
      to evaluate the survival and efficacy of Nivolumab treatment. A retrospective
      analysis was performed at a thoracic oncology service in a tertiary referral
      center (Tel-Aviv Sourasky Medical Center), on patients with NSCLC (squamous and
      non-squamous). All patients were treated with Nivolumab 3 mg/kg, administered
      intravenously every 2 weeks as part of a compassionate use program. The survival
      data was analyzed after 22 months. The overall survival (OS) was 34.9%, while the
      progression free survival (PFS) was 19.3%. The median PFS from the first dose of
      Nivolumab to treatment discontinuation was 4 months. A response assessment was
      performed in the 62 patients who received at least four cycles of Nivolumab, out
      of the 77 patient cohort. There was a complete response in 1 patient, a partial
      response in 11 patients, stable disease in 25 patients and progressive disease in
      25 patients. The observed response rate of Nivolumab as a service treatment in
      unselected patients with unknown PD-L1 status NSCLC was 19%. The disease control
      rate was 60%. In the present study Nivolumab was given to a cohort of patients
      representing those seen in daily clinical practice, as opposed to a clinical
      trial setting. Survival and efficacy results strongly support the continued use
      of Nivolumab as a treatment for NSCLC.

PMID- 30214731
TI  - Superiority of the 8th edition of the TNM staging system for predicting overall
      survival in gastric cancer: Comparative analysis of the 7th and 8th editions in a
      monoinstitutional cohort.
AB  - The present study was performed to evaluate the predictive capacity of the 8th
      edition vs. the 7th edition of the American Joint Committee on Cancer (AJCC)
      tumor-node-metastasis (TNM) staging system for overall survival (OS) of patients
      with gastric cancer. Data of eligible patients with gastric cancer in our
      institution between June 2004 and June 2014 were retrospectively reviewed. A
      total of 1,506 patients were followed up to July 2016, among whom 1,484 patients
      with complete stage information were included in the TNM staging analysis. A
      total of 339 (22.8%) patients presented stage migration, including 325 (21.9%)
      migrating to a lower tier and 14 (0.9%) to a higher tier. All patients with stage
      migration to a lower tier were in stage III, including 177 (54.5%) patients
      migrating from stage IIIB to IIIA, and 148 (45.5%) from stage IIIC to IIIB.
      Patients migrating from IIIB to IIIA yielded a median OS time and 5-year OS rate
      closer to those remaining in stage IIIA. Similarly, patients migrating from IIIC
      to IIIB yielded a median OS time and 5-year OS rate closer to those remaining in
      stage IIIB. The 7th edition of the staging system exhibited prognostic
      discrepancy in discriminating stage IIIA from IIIB on survival curves, which was
      improved in the 8th edition. The 8th edition had a better predictive capability
      of survival, as evidenced by a smaller value of -2log likelihood in the Cox
      proportional regression model (7th edition 4738.859 vs. 8th edition 4736.683).
      Therefore, the present study demonstrated that the 8th edition of the AJCC TNM
      staging system is superior to the 7th edition in predicting the OS of patients
      with gastric cancer.

PMID- 30214732
TI  - Incidental discovery of mucinous adenocarcinoma of the prostate following
      transurethral resection of the prostate: A report of two cases and a literature
      review.
AB  - Mucinous carcinoma is an unusual subtype of prostate cancer. In particular,
      mucinous adenocarcinomas identified following transurethral resection of the
      prostate (TURP) are extremely rare. The present study conducted are retrospective
      analysis of two cases of mucinous carcinoma of the prostate, which were
      incidentally diagnosed following histological examination of the specimens
      obtained by TURP. The pathological findings, treatment regimen and clinical
      course of the two cases were reviewed. One of the patients, whose surgical
      specimen stained positive for carcinoembryonic antigen (CEA) and negative for
      prostate-specific antigen (PSA), did not respond to androgen deprivation therapy
      (ADT). However, the other patient, whose specimen stained positive for PSA, was
      responsive to ADT, resulting in a better prognosis. Therefore, absence of PSA
      staining in surgical prostate specimens may be associated with a poor response to
      ADT and a worse prognosis.

PMID- 30214733
TI  - Primary adrenal teratoma: A case series and review of the literature.
AB  - Primary adrenal teratoma is a rare type of cancer. Of the 338 patients who
      underwent adrenalectomy during this study, only 2 (aged 69 and 29 years) were
      diagnosed with adrenal teratoma and underwent laparoscopic retroperitoneal
      adrenalectomy. For the purposes of the present study, the term 'adrenal teratoma'
      was searched in the PubMed database, and 237 articles published between June 1952
      and March 2017 were retrieved. However, we were only able to identify 10 relevant
      studies. In total, these studies reported a series of 18 cases of primary adrenal
      teratoma in patients aged >16 years, another 8 cases of adult adrenal
      retroperitoneal teratoma, and 7 cases of adrenal teratoma in children aged <16
      years. In the 18 cases aged >16 years, the age range was 17-61 years (mean +/-
      standard deviation, 33.06+/-15.47 years), the median tumor diameter was 8.25 cm
      and 13 patients (72.22%) were female. Almost all patients underwent laparoscopic
      surgery between 2006 and 2017 (75%). Among the 7 cases of adrenal teratoma in
      children under the age of 16 years, 5 cases (71.43%) were male, the median tumor
      diameter was 10 cm, the oldest patient was aged 8 years, 5 cases (71.43%) were
      selected for open surgical resection of the tumor, and 5 cases (71.43%) were
      followed up without recurrence or death. These data indicate that primary adrenal
      teratomas in children are rarer compared with adults. Although the data are
      limited, it was observed that the clinical symptoms of primary adrenal teratoma
      are not typical, the preferred treatment is retroperitoneal laparoscopic surgery,
      and the prognosis is favorable. The aim of the present study was to elucidate the
      clinical characteristics associated with primary adrenal teratoma, in order to
      further raise awareness of this rare disease.

PMID- 30214734
TI  - A cross-sectional survey of methods for controling hand-foot syndrome in patients
      receiving capecitabine treatment.
AB  - Medical personnel actively provide patients taking capecitabine with information
      on the items to prevent and treat hand-foot syndrome (HFS). However, they are
      typically unable to ascertain the extent of patient compliance with the
      recommended items. Thus, the aim of the present study was to ascertain the
      association between patient compliance with preventative measures for HFS and the
      development of HFS. Subjects included 90 patients who were treated with a drug
      regimen that included capecitabine. Patients were treated at one of four
      facilities between July 2015 and January 2017. The main parameters studied were
      the extent to which items to prevent and treat HFS were (or were not) followed,
      and the associaiton between this extent and the development of HFS symptoms. A
      manual prepared by a pharmaceutical company that manufactures capecitabine
      describes 15 routine items to follow in order to prevent and treat HFS. The two
      activities patients most often performed were 'applying a moisturizer' (74.1%)
      and 'keeping one's skin clean (e.g., washing one's hands and feet)' (64.7%). The
      two activities patients least often performed were 'using sunscreen on exposed
      areas' (14.1%) and 'using soft insoles' (11.8%). Patients who performed more
      items to prevent and treat HFS were significantly less likely to develop symptoms
      of HFS (P=0.022). Based on these findings, it is recommended that medical
      personnel provide instructions to the patients regarding the specific items
      necessary to prevent and treat HFS, and to follow-up with the patients regarding
      their compliance, with an emphasis on the items they are less likely to take and
      on the instructions to avoid external irritants. Following these guidelines
      should lead to qualitative improvement in HFS management.

PMID- 30214736
TI  - Case reports from low- and middle-income countries: supporting clinical evidence
      for those most in need.

PMID- 30214735
TI  - Efficacy of vemurafenib in a heavy smoker with BRAF-mutated lung adenocarcinoma:
      A case report and literature review.
AB  - At present, research on BRAF gene mutations appears to be mainly focused on
      melanoma rather than non-small-cell lung cancer (NSCLC). We herein describe the
      case of a patient with BRAF V600E-mutated advanced NSCLC, whose symptoms were
      relieved and computed tomography imaging revealed partial response to vemurafenib
      following failure of chemotherapy. This case demonstrates the promising prospects
      of BRAF inhibitor treatment in patients with BRAF-mutated NSCLC. Targeted
      therapies have significantly modified the treatment of NSCLC. However, tumor
      tissue is frequently hard to obtain, whereas the coincidence rate of gene
      mutations between the plasma and tumor tissue is 60-80%. Therefore, in cases
      where tumor tissue is difficult to obtain, plasma next-generation sequencing may
      be used to detect gene mutations, which can overcome the limitations of gene
      detection. Furthermore, due to the tumor heterogeneity, different patients
      exhibit different gene mutation abundance. Research has demonstrated that
      mutation abundance is associated with the therapeutic efficacy of epidermal
      growth factor receptor-tyrosine kinase inhibitors. However, the association
      between BRAF mutation abundance and the therapeutic effect of BRAF inhibitors
      requires further verification.

PMID- 30214737
TI  - Uterocutaneous fistula due to held placenta in a low resource setting.
AB  - Postcesarean section complication rate is higher in LMIC (Low and Middle Income
      Countries) due to lack of resources and specialists availability. A completely or
      incompletely held infected placenta might underlie a dehiscent cesarean section
      wound. Humanitarian and local surgeons should consider this differential
      diagnosis and be ready to practice hysterectomies when needed.

PMID- 30214738
TI  - Lead failure in transvenous implantable cardioverter defibrillator: a new
      opportunity for an effective management.
AB  - In case of transvenous defibrillator lead failure, a subcutaneous defibrillator
      may be implanted and the lead may be abandoned in order to avoid particular risk
      situations. For patients who require pacing and with an operational atrial lead,
      the transvenous ICD may be also maintained to ensure antibradycardia support.

PMID- 30214739
TI  - A de novo derivative Y chromosome (partial Yq deletion and partial duplication of
      Yp and Yq) in a female with disorders of sex development.
AB  - We report an atypical disorders of sex development (DSD) case with no mutation of
      SYR gene but partial Yq deletion and partial duplication of Yp and Yq. This case
      emphasizes duplicated region Yp11.2->Yq11.223 with partial deletion of Yq11.223
      >Yqter most probably perturbed the sex differentiation and led to female
      phenotype.

PMID- 30214740
TI  - Peritonitis from injury of an aberrant subvesical bile duct during laparoscopic
      cholecystectomy: A rare case report.
AB  - Aberrant subvesical bile ducts are rare anatomical structures. Damage to these
      ducts leads to bile leakage and can result in life-threatening complications.
      Surgeons should be cautious that such a structure may be present, and surgery
      should be performed with the correct surgical field to prevent damage to these
      structures.

PMID- 30214741
TI  - Cardiac biopsy with intracardiac echocardiographic guidance for successful
      diagnosis of cardiac lymphoma.
AB  - The diagnosis and appropriate treatment of cardiac lymphoma are often delayed by
      the difficulty in obtaining heart tissue biopsies. Intracardiac echocardiography
      guided biopsy can improve the prognosis of cardiac lymphoma by decreasing
      postbiopsy complications and increasing biopsy quality, allowing collection of
      sufficient material for multilateral analysis.

PMID- 30214742
TI  - Alternating hyperthyroidism and hypothyroidism in Graves' disease.
AB  - Spontaneously oscillating thyroid function in Graves' disease is a rare
      phenomenon. Switching between TSH receptor stimulating antibodies (TSAb) and TSH
      receptor blocking antibodies (TBAb) most likely accounts for presentations of
      alternating hyperthyroidism and hypothyroidism. To achieve stability of thyroid
      function, definitive therapy is recommended to remove the pathological thyroid.

PMID- 30214743
TI  - Dental erosion caused by Granny Smith apples: An evidence-based case report and 1
      year follow-up.
AB  - Apples, if indiscriminately consumed without appropriate preventive measures to
      check erosion, can cause accelerated wear of the teeth.Dentists must be fully
      aware of the intrinsic and extrinsic factors that cause erosive tooth wear.
      Management strategy for tooth erosion depends on the severity of erosion,
      esthetics, function, and patient's preference.

PMID- 30214744
TI  - Urethral steinstrasse: Day case care.
AB  - Urethral steinstrasse is rare. Only a few cases of spontaneous or
      postinterventional urethral steinstrasse have been reported in pediatric and
      adult patients. We report a case of a 52-year-old Nigerian man with a secondary
      urethral steinstrasse, and the treatment options possible, as day case
      procedures, under caudal anesthesia.

PMID- 30214745
TI  - A case of antithyroid drug-induced agranulocytosis from a second antithyroid
      drugs (ATD) administration in a relapsed Graves' disease patient who was tolerant
      to the first ATD treatment.
AB  - Agranulocytosis is a rare side effect of antithyroid drugs (ATD) that usually
      develops within the first 3-6 months after starting treatment. We present a 64
      year-old patient who developed agranulocytosis after starting ATD to treat
      relapsed Graves' disease. This patient had tolerated the first course of ATD for
      72 months. This was an unusual case in which a serious side effect developed
      during a second ATD course. It is essential that clinicians remain vigilant to
      the fact that antithyroid drugs can induce agranulocytosis several years after
      initiated.

PMID- 30214746
TI  - Safe delivery of lung stereotactic body radiation therapy in a patient with a
      left ventricular assist device and implantable cardioverter defibrillator.
AB  - This is the first case to discuss the safe delivery of stereotactic body
      radiation therapy to a left lower lobe lung nodule in a patient with a third
      generation left ventricular assist device (Heartware(r)) and implantable
      cardioverter defibrillator.

PMID- 30214747
TI  - A novel semi-solidifying liquid formula via the nasogastric route to maintain
      enteral nutrition in the event of recurrent aspiration pneumonia: A case report.
AB  - Recurrent aspiration pneumonia can impede the continuation of enteral nutrition.
      Semi-solid feeds have been demonstrated to reduce the incidence of aspiration
      pneumonia but are difficult to administer via the nasogastric tube. A novel semi
      solidifying enteral formula may be used instead to avoid the occurrence of severe
      gastroesophageal reflux.

PMID- 30214748
TI  - Gastrointestinal tract metastasis of mandibular diffuse large B-cell lymphoma.
AB  - Not only diffuse large B-cell lymphoma is a malignancy, but also is initially and
      orally diagnosed in early stages. However, it could be misdiagnosed with other
      oral pathologies. However yet, early diagnosis is still crucial for the
      prognosis, morbidity, and mortality in such cases. Additionally, whole-body
      scanning with positron emission tomography/computed tomography should be
      performed for diagnosis and treatment process.

PMID- 30214749
TI  - Application of the modified Zajicek criteria to diagnose probable spinal cord
      neurosarcoidosis.
AB  - Neurosarcoidosis represents a significant diagnostic challenge, as clinical
      features overlap with other neuroinflammatory conditions, and biopsy of affected
      neuronal tissue is often high risk or not feasible. Here we highlight application
      of the modified Zajicek criteria to diagnose probable spinal neurosarcoidosis in
      the absence of histology from affected neuronal tissue.

PMID- 30214750
TI  - Polymyositis as a manifestation of chronic graft-versus-host disease after allo
      HSCT.
AB  - Patients who received allogeneic haematopoietic stem cell transplantation (allo
      HSCT) may develop T cell-mediated immunologic injury to muscles, recapitulating
      the characteristics of polymyositis clinically and pahtologically. Polymyositis
      is a rarely reported complication of graft-versus-host disease (GVHD), which
      often responds well to corticosteroids and immunosuppressive treatment.

PMID- 30214751
TI  - Subcutaneous implantable defibrillator in dextrocardia secondary to Lobectomy.
AB  - Knowledge of anatomy is vital preimplant to screen the patient for the
      subcutaneous implantable defibrillator (S-ICD), particularly those who have
      previously had thoracic surgery. X-ray screening in these patients is highly
      recommended.

PMID- 30214752
TI  - Cutaneous mucormycosis caused by Saksenaea vasiformis in a patient with systemic
      lupus erythematosus.
AB  - Primary cutaneous mucormycosis due to Saksenaea vasiformis is a rare clinical
      manifestation and the actual number of the disease condition is underestimated
      due to lack of sporulation in the absence of molecular diagnosis. Combination
      therapy of antifungal and repetitive debridement is mandatory in curing the
      patients.

PMID- 30214753
TI  - Management of a failed endodontic treatment for a maxillary second molar with two
      separate palatal roots.
AB  - Complexity of root canal system and variations in internal anatomy of teeth
      require careful analysis of preoperative cone beam computed tomography or
      multiangle radiographs to locate and identify possible extra roots or canals. A
      fourth canal in upper molars is expected, and much effort should be made when
      planning the endodontic treatment to avoid missing a canal.

PMID- 30214754
TI  - Conventional and conservative management of placenta accreta is two ends of a
      single continuum: A report of three cases and literature review.
AB  - Placenta accreta (PA) is a critical condition that represents a significant
      source of morbidity and mortality observed in women with multiple prior cesarean
      sections. Precise prenatal identification of affected pregnancies permits optimal
      obstetric management. Antenatal diagnosis leads to less blood loss and a
      requirement for blood transfusion than women diagnose during cesarean section.

PMID- 30214755
TI  - Rupture of hidden abnormal myometrial vessels during cesarean delivery of a
      patient with subserosal leiomyoma: A possible pathogenesis of sudden-onset
      disseminated intravascular coagulation.
AB  - We report a case of sudden-onset disseminated intravascular coagulation during
      cesarean delivery for a patient with a subserosal leiomyoma. Rupture of hidden
      anastomotic vessels resulted in a significant decrease in fibrinogen levels and
      uncontrolled bleeding. Uterine venous flow disturbance caused by subserosal
      leiomyoma compression can possibly cause such a situation.

PMID- 30214756
TI  - Identification of a BRCA2 mutation in a Turkish family with early-onset breast
      cancer.
AB  - We used a multi-gene panel testing to identify the germline variants in a mother
      daughter pair with early-onset breast cancer, and detected one pathogenic protein
      truncating variant in BRCA2. Our results highlight the importance of genetic
      testing in identifying the pathogenic mutation running in cancer families.

PMID- 30214757
TI  - Pseudotumor complicating a well-fixed ceramic-on-polyethylene total hip
      arthroplasty.
AB  - A suspicious area surrounding hardware components, usually following
      arthroplasty, should raise awareness to a possible particle related disease. Even
      in the presence of confusing or less typical symptoms, clinicians and surgeons
      must join efforts to diagnose and treat the patient effectively and in the
      appropriate time.

PMID- 30214758
TI  - Plasma cell mucositis of the larynx.
AB  - Stridor is a symptom with a number of causes, usually identified through careful
      history taking and examination. When the cause is unclear, as in our case,
      consider investigations such as blood tests, biopsy, and imaging. We discuss a
      rare diagnosis of plasma cell mucositis, treated with some success by steroids.

PMID- 30214759
TI  - Bilateral knee septic arthritis: Was it from sternal wound?
AB  - Polyarticular septic arthritis is a rare but life-threatening condition and
      should not be underestimated. Clinicians should look for potential source of
      infection, either local spread or hematogenous distribution. However, this should
      not delay the main treatment for septic arthritis.

PMID- 30214760
TI  - A case of non-alcoholic steatohepatitis complicated with severe acute
      pancreatitis induced by decreased lipoprotein lipase and hepatic triglyceride
      lipase activity levels in a young Japanese woman.
AB  - We report a case of non-alcoholic steatohepatitis complicated with acute
      pancreatitis induced by hypertriglyceridemia in a young Japanese woman. A precise
      examination of the lipid profile showed decreased lipoprotein lipase (LPL) and
      hepatic triglyceride lipase activity levels, while the LPL mass was at the
      minimum level of the normal range.

PMID- 30214761
TI  - Novel TRPV4 variant causes a severe form of metatropic dysplasia.
AB  - We present a girl born with a frontal bossing, short neck, bell-shaped thorax,
      short limbs with prominent joints, and a tail-like coccygeal appendage. Genetic
      screening of TRPV4 identified a novel de novo heterozygous missense variant. We
      believe the variant causes the severe form of metatropic dysplasia in this
      patient.

PMID- 30214762
TI  - Refractory chronic "ITP": When platelet size matters.
AB  - Inherited conditions associated with thrombocytopenia should be included in the
      differential diagnosis of young patients with refractory immune thrombocytopenia
      (ITP), even in the absence of a positive family history. Early identification of
      such conditions is of vital importance in order to reach the right diagnosis and
      avoid unnecessary or even harmful medication.

PMID- 30214763
TI  - Anticoagulation in atrial fibrillation with factor X deficiency-A management
      dilemma.
AB  - Factor X (FX) deficiency is a rare bleeding disorder. There is currently no clear
      guideline or recommendation for the appropriate selection of anticoagulation and
      management of patients with FX deficiency who require anticoagulation. We shared
      our experience in managing such patient, and we further discussed other possible
      treatment options.

PMID- 30214764
TI  - Congenital diaphragmatic hernia in a case of Cat eye syndrome.
AB  - Our findings extend the phenotypic spectrum of Cat eye syndrome, a disorder with
      wide clinical variability. The potentially life-threatening complications of
      congenital diaphragmatic hernia should be considered in genetic counseling and
      prenatal diagnostic.

PMID- 30214765
TI  - Atrial fibrillation, an epiphenomenon of acute Stanford type-A aortic dissection
      with suspected intimo-intimal intussusception.
AB  - Supraventricular arrhythmias can sometimes be "only" epiphenomena appearing
      during acute hypoxia, pneumonia, pulmonary embolism, and thrombosis. Indeed,
      atrial fibrillation is not rare in acute aortic dissection as it is estimated in
      about one half of patients and may be secondary to a perfusion deficit of the
      sinoatrial node artery.

PMID- 30214766
TI  - An implantable cardioverter defibrillator in a patient with triple mechanical
      valves.
AB  - A patient with permanent atrial fibrillation, triple mechanical prosthetic valve
      replacements, and nonischemic cardiomyopathy presented with symptomatic high
      grade atrioventricular block. A transvenous implantable cardioverter
      defibrillator system was achieved with the defibrillator lead and bipolar pace
      sense lead in separate anterolateral branches of the coronary sinus with
      successful defibrillation testing.

PMID- 30214767
TI  - Biological implant-associated granulomatous inflammation resulting in secondary
      hypercalcemia and azotemia in a dog.
AB  - Implant associated granulomatous inflammation causing hypercalcemia can occur
      following use of commercial xenogeneic pericardial tissue patches in dogs.
      Removal of the implant can result in resolution of the hypercalcemia, suggesting
      a causal relationship between the tissue reaction to a xenogeneic implant and
      development of hypercalcemia.

PMID- 30214768
TI  - Preoperative administration of eculizumab to prevent surgery-triggered hemolysis
      during cesarean section with paroxysmal nocturnal hemoglobinuria.
AB  - Eculizumab in pregnancy has been reported to be effective in improving outcomes
      in patients with paroxysmal nocturnal hemoglobinuria. However, a cesarean section
      may result in surgery-triggered hemolysis. An additional dose of eculizumab just
      prior to delivery is an appropriate choice to prevent postoperative hemolysis.

PMID- 30214769
TI  - Postoperative granulomatous peritonitis mimicking abdominal tuberculosis.
AB  - Granulomatous peritonitis represents a rare postoperative complication that
      should be considered as important differential diagnosis in all patients who
      present to the hospital with abdominal pain, abdominal tenderness, and fever
      after abdominal surgery. Clinical distinction from abdominal tuberculosis remains
      a diagnostic challenge and requires thorough histopathological and
      microbiological examination.

PMID- 30214770
TI  - The first case of deafness-dystonia syndrome due to compound heterozygous
      variants in FITM2.
AB  - We report the second known family affected by deafness-dystonia syndrome
      associated with loss of function of FITM2. Our patient is compound heterozygous
      for pathogenic FITM2 variants, while affected siblings in the first report were
      homozygous. This case provides evidence that this novel genetic disorder is
      associated with autosomal recessive inheritance.

PMID- 30214771
TI  - EBV-positive, HHV8-negative large B-cell lymphoma with an unusual germinotropic
      growth pattern in an immunocompetent patient.
AB  - Clinicopathologic and cytogenetic findings of an unusual EBV+ve, HHV8-ve
      germinotropic lymphoma, with a nongerminal center immunophenotype occurring in an
      immunocompetent individual, are presented. A comprehensive literature search
      revealed a single report of three similar cases. These may represent a unique
      subset of EBV-positive large B-cell lymphomas in immunocompetent individuals.

PMID- 30214772
TI  - Late recovery from unconsciousness in a patient with severe posterior reversible
      encephalopathy syndrome.
AB  - This study describes a patient case presenting with severe posterior reversible
      encephalopathy syndrome (PRES) who needed 3 months to recover impaired
      consciousness. We discuss the protracted time course needed to deal with severe
      PRES cases. Positive prognoses can emerge from these situations if treatment is
      prompt and precise.

PMID- 30214773
TI  - Sjogren's syndrome concurrent with protein-losing gastroenteropathy with
      secondary systemic capillary leak syndrome : A case report.
AB  - Sjogren's syndrome concurrent with protein-losing gastroenteropathy can develop
      into secondary systemic capillary leak syndrome. Thus, it is important to
      diagnose the condition as soon as possible and simultaneously administer
      treatment for Sjogren's syndrome, protein-losing gastroenteropathy, and systemic
      capillary leak syndrome.

PMID- 30214774
TI  - Diffuse cutaneous mastocytosis with novel somatic KIT mutation K509I and
      association with tuberous sclerosis.
AB  - Diffuse cutaneous mastocytosis (DCM) is a rare but potentially fatal condition
      when diagnosis and targeted treatments are delayed. This case illustrates the
      life-threatening complications in DCM and reviews the currently available
      treatments. To our knowledge, this is the first report of mastocytosis with
      somatic K509I mutation and concomitant tuberous sclerosis.

PMID- 30214775
TI  - Reduced-toxicity allogeneic hematopoietic stem cell transplantation in congenital
      sideroblastic anemia.
AB  - The case of an infant girl with severe congenital sideroblastic anemia associated
      with a novel molecular defect in mitochondrial transporter SLC25A38 is presented.
      Her transfusion dependence was fully reversed following allogeneic hematopoietic
      stem cell transplantation using a modified reduced-intensity conditioning
      regimen, and she remains healthy 5 years posttransplant.

PMID- 30214776
TI  - Clinical case report on treatment of Listeria monocytogenes meningoencephalitis:
      Intrathecal injection.
AB  - This article mainly reports the process of clinical diagnosis and treatment of a
      misdiagnosed Listeria monocytogenes meningoencephalitis. The patient's condition
      is aggravated because of the ineffective prophase therapy. In the later stage, we
      were mainly through combined antibiotics and given proper routes of
      administration, so that patient can recover quickly.

PMID- 30214777
TI  - Secondary sclerosing cholangitis following extracorporeal membrane oxygenation
      for acute respiratory distress in polytrauma.
AB  - Secondary sclerosing cholangitis is a recently identified phenomenon affecting
      the biliary tree. A subtype has been described in critically ill patients (SSC
      CIP). However, underlying mechanisms are unknown, and few cases have been
      reported following extracorporeal membrane oxygenation (ECMO). We present a 19
      year-old male with SSC-CIP after ECMO following major trauma.

PMID- 30214778
TI  - Third molar in the orbital floor: A precarious presentation of odontogenic
      keratocyst-A case report and review of literature.
AB  - The case illuminates the likelihood of a dental pathology presenting with
      discrete signs and symptoms and the importance of the differential diagnosis of
      some incongruent clinical entities. The purpose of this article was to present a
      case report of odontogenic keratocyst (OKC) arising in the orbital floor, finding
      the common thread in rare pathology, and highlighting the aberration in our
      treatment plan by collating all the wealth of information published in the
      literature.

PMID- 30214779
TI  - Massive air embolism as a complication of upper gastrointestinal endoscopy: A
      case report illustrating a stroke mimic, literature review, and suggested
      management.
AB  - Cerebral air embolism should be considered in case of stroke symptoms during any
      invasive procedure. Transport to a hospital with neurosurgical/hyperbaric oxygen
      treatment (HBOT) facility could improve the outcome for the patient. Absence of
      air on computed tomography (CT) scan should not disqualify a patient from HBOT if
      air embolism is suspected.

PMID- 30214780
TI  - Treatment of solar lentigines using a combination of picosecond laser and
      biophotonic treatment.
AB  - Treating solar lentigines using picosecond-switched lasers that selectively
      remove the excess pigment was combined with Kleresca(r) biophotonic treatment.
      This therapy uses fluorescent light energy to stimulate healing by increasing
      collagen production and reducing inflammation. Combining these therapies
      successfully removed solar lentigines and achieved normalized and rejuvenated
      treated skin.

PMID- 30214781
TI  - Atypical onset of nephropathic infantile cystinosis in a Russian patient with
      rare CTNS mutation.
AB  - We report a Russian patient with atypical onset of infantile nephropathic
      cystinosis. The disease debuted with vomiting and loss of weight and motor
      skills. Nephropathic changes appeared 6 months after onset of disease. Exome
      sequencing can be useful for diagnosing cystinosis in patients with neurological
      abnormalities before onset of nephropathic symptoms.

PMID- 30214782
TI  - Vulvar intraepithelial neoplasia treated with a combination of surgical excision
      and laser ablation during pregnancy.
AB  - Most vulvar intraepithelial neoplasias are associated with human papillomavirus.
      However, detailed surgical plans during pregnancy are rarely discussed. We
      suggest that the treatment policy should focus on performing surgical excision on
      multifocal lesions, combined surgical excision/laser ablation on single lesions,
      and preserving unaffected perineal skin, if possible.

PMID- 30214783
TI  - Prenatally diagnosed large mediastinal lymphangioma: A case report.
AB  - Thoroughly planned labor with immediate postnatal resuscitation and percutaneous
      decompression is mandatory for a large mediastinal lymphangioma that compromises
      the cardiopulmonary function, and close observation with the administration of
      Eppikajutsuto (TJ-28), a Japanese herbal medicine, may be a reasonable treatment,
      especially when resection of the lesion seems technically challenging.

PMID- 30214785
TI  - Hypopharyngeal lipoma-A diagnostic work up.
AB  - It is important to examine the pharynx through nasoendoscopic examination in
      patients that present with dysphagia, to look for pharyngeal masses. Magnetic
      resonance imaging can accurately diagnose lipoma in the pharynx region.

PMID- 30214784
TI  - Pedunculated small bowel lipoma with heterotopic pancreas causing
      intussusception.
AB  - Small bowel intussusception is a relatively uncommon cause of abdominal pain. The
      diagnosis is often delayed due to vague symptoms and limitations with current
      endoscopic and radiographic approaches to evaluate the small bowel lumen.
      Treatment often requires surgical resection, which can usually be performed in a
      minimally invasive fashion.

PMID- 30214786
TI  - Congenital multiple coronary arteriovenous fistulas.
AB  - Coronary arteriovenous fistulas are congenital or acquired abnormalities
      characterized by abnormal communication between the coronary circulation and
      cardiac chambers or other vessels. Frequently, patients are asymptomatic and
      their diagnosis can be carried out incidentally by echocardiography. Knowing the
      echocardiographic findings characteristic of this malformation will prevent the
      diagnosis from going unnoticed.

PMID- 30214787
TI  - A rare complication of pacemaker implantation.
AB  - Lead perforation is a life-threatening rare complication of pacemaker or
      defibrillator lead implantation. Clinical examination, electrocardiogram, device
      interrogation, echocardiography, chest x-ray, and chest computed tomography scan
      can help in the diagnosis. Clinicians should be aware because early diagnosis and
      treatment are the cornerstones for achieving a better outcome.

PMID- 30214788
TI  - Exaggerated arthropod assault: Eosinophilic dermatosis in a patient with small
      lymphocytic lymphoma.
AB  - Dermatologic reactions are commonly encountered in clinical practice. Providers
      must be aware of both the common and uncommon etiologies leading to these
      eruptions, particularly in patients with underlying malignancies. Establishing
      the appropriate etiology directs treatment of these conditions, which may be
      therapy directed at the malignancy itself.

PMID- 30214789
TI  - Young man with acute pain in the hypogastrium: What is the diagnostic?
AB  - Congenital renal anomalies can stay asymptomatic even until adult age and be
      revealed by occurrence of complications. Clinicians should keep in mind this
      eventuality, especially in the countries where screening for congenital
      abnormalities is not adopted. Ultrasound in front of abdominal pain is useful and
      can sometimes rectify the diagnosis.

PMID- 30214790
TI  - Disappearance of multiple pancreatic cysts after prednisolone treatment in a
      patient with autoimmune pancreatitis.
AB  - Autoimmune pancreatitis (AIP) with multiple pancreatic cysts is rare. The severe
      narrowing of the branched pancreatic ducts found in active AIP with a chronic
      pancreatitis background may have caused pancreatic juice outflow obstruction,
      resulting in multiple cysts. Oral steroid therapy resolved the stenosis,
      resulting in disappearance of the cysts.

PMID- 30214791
TI  - Wunderlich syndrome.
AB  - End-stage renal disease (ESRD) patients are predisposed to bleeding diathesis in
      the setting of uremic platelet dysfunction and endothelial abnormalities. One
      should have high index of suspicion for spontaneous renal hemorrhage when these
      patients present with abdominal pain and/or unexplained drop in hemoglobin and
      appropriate imaging should be undertaken without delay.

PMID- 30214792
TI  - GISToscopy.
AB  - Gastrointestinal stromal tumors (GIST) tumors are a rare, though typical cause
      for upper GI bleeding. Excavated ulcerated lesions are common; however, a clear
      cut visualization of the tumor surface ("GISToscopy") itself has not yet been
      reported. In line, careful biopsy taking streamlines the diagnostic work-up by
      providing pathologic diagnosis.

PMID- 30214793
TI  - Acute respiratory distress syndrome caused by salicylate intoxication.
AB  - Salicylate-induced acute respiratory syndrome (ARDS) is a well-known entity
      occurring in 35% of salicylate-intoxicated patient. Careful history taking,
      physical examination, arterial blood gas analysis, and measurement of serum
      salicylate concentration will lead to early recognition to initiate appropriate
      treatment.

PMID- 30214794
TI  - Unusual metastases of melanoma.
AB  - Malignant melanoma is a very aggressive tumor. Immune and targeted therapy could
      prolong patient's clinical benefit and survival, but the correct sequence of
      therapies has still to be defined.

PMID- 30214795
TI  - Two transplant renal arteries: One important lesson.
AB  - High index of suspicion is required for ischemic nephropathy in renal transplant
      recipients presenting with unexplained acute kidney injury, as it is potentially
      reversible. Carbon dioxide (CO2) angiogram is a good alternative to evaluate
      vasculature in patients with renal dysfunction where iodinated contrast is
      relatively contraindicated.

PMID- 30214796
TI  - Hyperplastic gastric polyp with foci of ossification.
AB  - Stromal ossification has been reported in relation with gastrointestinal (GI)
      cancers. Heterotopic ossification of benign gastric polyps with bone formation is
      rarely documented and sometimes associated with calcification. Thus, the presence
      of foci of metaplastic bone (FMB) does not always imply GI cancer.

PMID- 30214797
TI  - Airway foreign body manifested as a coin lesion.
AB  - Foreign body aspiration is a potentially life-threatening event. The nature of
      the inhaled objects is highly variable, ranging from organic to inorganic
      material. Although most pills are radiolucent, lanthanum carbonate is radiopaque
      and may be identified on chest X-rays.

PMID- 30214798
TI  - Severe duodenal stenosis due to rupture of pancreaticoduodenal artery aneurysm.
AB  - When a patient complains of nausea, gastrointestinal endoscopy tends to be the
      first-choice diagnostic method. However, physicians must rule out the possibility
      of aneurysm rupture by careful physical assessment before performing
      gastrointestinal endoscopy, which can be extremely dangerous.

PMID- 30214799
TI  - Blood finds its own way: Axillary vein thrombosis with extensive chest-wall
      collaterals.
AB  - Hemodialysis catheters are associated with upper extremity deep vein thrombosis,
      and chronic venous occlusion leads to the formation of collateral pathways.
      Knowledge of these pathways aids in accurate interpretation of upper extremity
      venograms. Arteriovenous fistula is the preferred access for chronic
      hemodialysis, and long-term use of catheters should be avoided.

PMID- 30214800
TI  - Bilateral semilunar perihilar opacities in a patient with pulmonary hypertension.
AB  - Pulmonary arterial aneurysm is a rare entity with a high mortality if left
      untreated. Pulmonary arterial hypertension is an important cause of PAAs although
      other infective and auto-immune causes must be excluded when an aneurysm is
      identified.

PMID- 30214801
TI  - Rail-tracking calcification of lower limb arteries.
AB  - Peripheral artery disease has increased worldwide in recent years.
      Revascularization of severely calcified vessels is a technically challenging
      problem. Clinicians should recognize that excessive arterial calcification can
      occur even in nonelderly patients with less arteriosclerosis risk, leading to
      severe lower limb ischemia.

PMID- 30214802
TI  - Diode laser treatment of venous lake of the lip.
AB  - The diode laser promotes regression of the small venous lake of the lip by forced
      dehydration with induced photocoagulation of the lesions, with an uneventful
      postoperative course and anesthetic sequelae.

PMID- 30214803
TI  - Specialized group intervention for compulsive exercise in inpatients with eating
      disorders: feasibility and preliminary outcomes.
AB  - Background: Patients with eating disorders (ED) often suffer from compulsive
      exercise behavior, which is associated with lower short-term response to
      treatment and poorer long-term outcome. Evidence-based interventions specifically
      targeting compulsive exercise behavior have been scarce so far. We developed a
      manualized group therapeutic approach integrating cognitive-behavioral therapy,
      exercise therapy and exposure with response management to promote healthy
      exercise behavior. Our objective was to examine the feasibility and acceptance of
      this new approach as add-on to regular inpatient treatment in a pilot study.
      Additionally, we wanted to estimate preliminary effect sizes. Methods: Thirty-two
      female, adolescent and adult eating disordered inpatients were recruited.
      According to the 4th ed. of the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-IV), twenty-six patients met criteria for Anorexia nervosa (AN),
      two for Bulimia nervosa and four for eating disorder not otherwise specified.
      Semi-structured interviews were conducted for qualitative evaluation of
      feasibility and acceptance of the new intervention. Patients completed the
      Commitment to Exercise Scale (CES) and the Compulsive Exercise Test (CET) for
      assessment of compulsive exercise, the Eating Disorder Inventory-2 for assessment
      of eating disorder pathology, the Beck Depression Inventory-II and Brief Symptom
      Inventory for assessment of depressive and general psychopathology and the
      Emotion Regulation Skills Questionnaire for assessment of emotion regulation
      before the beginning and at the end of the group intervention. Additionally,
      weight gain was monitored. Results: Feasibility of our approach was confirmed.
      All patients reported a high satisfaction with both structure and content of the
      group. Between pre- and post-intervention, patients showed significant reductions
      in compulsive exercise (effect size CES: 1.44; effect size CET total: 0.93),
      drive for thinness (effect size: 0.48), depressive symptoms (effect size: 0.36),
      general psychopathology (effect size: 0.29) and acceptance of emotions (effect
      size: - 0.62). Patients with AN also showed significant mean weight gain during
      the intervention (effect size: - 0.44). Conclusions: Results of our pilot study
      indicate that our integrative approach to compulsive exercise in ED patients
      might represent a promising new therapeutic option. Feasibility and acceptance of
      the intervention were confirmed. Preliminary effect sizes on most outcomes were
      promising. As improvements in Body-mass-index, eating disorder and general
      psychopathology are also to be expected by routine inpatient treatment, a large
      randomized trial is currently underway to evaluate the efficacy of this new
      intervention.

PMID- 30214805
TI  - Treatment of penile lichen sclerosus with topical corticosteroids for over 25
      years' duration: A case report.
AB  - Topical corticosteroids are currently recommended only for short-term management
      of flares of lichen sclerosus, with efficacy in halting disease progression.
      Given the chronic nature of this condition, there is a lack of literature
      surrounding the chronic effects of topical corticosteroids on the male genitalia
      with many dermatologists avoiding prescribing long term. This case report aims to
      provide anecdotal observation for the long-term use of topical corticosteroids
      and details the long-term follow-up of an individual who used potent and
      superpotent topical corticosteroids for over 25 years without significant
      demonstrable side effects. A short review on relevant literature is provided.

PMID- 30214804
TI  - Prevalence of disturbed eating behavior and associated symptoms of anxiety and
      depression among adult males and females with type 1 diabetes.
AB  - Background: The increased prevalence of disturbed eating behaviors (DEB),
      depression, and anxiety in type 1 diabetes (T1D) is generally well established;
      however the majority of existing research to date has focused on female
      adolescents and young adults. Data on males and older females is scarce. The aim
      of this study was to assess prevalence of DEB and symptoms of depression and
      anxiety among adult males and females with type 1 diabetes, to investigate
      differences between individuals scoring below and above the cut-off on
      psychopathology, and to examine patterns of eating disorder psychopathology by
      age and weight. Methods: A total of 282 adults with type 1 diabetes aged 18-79
      years participated in the study. Measures included the Diabetes Eating Problem
      Survey - Revised (DEPS-R), the Hospital Anxiety and Depression Scale (HADS), and
      clinical data from the Norwegian Quality Improvement of Laboratory Examinations
      (NOKLUS) system. Results: A total of 20.3% of the whole sample (13.3% among males
      and 24.8% among females) scored above the DEPS-R cut-off score for DEB. As for
      depression and anxiety, the prevalence in the whole sample was 6.2% and 19.0%,
      respectively. The prevalence was generally higher in females than males across
      all psychopathology measures. HbA1c was significantly associated with the DEPS-R
      total score (p < .01) among females, but not with depression and anxiety. Mean
      DEPS-R score decreased with increasing age, and when our previous reported data
      from children and adolescents are included, a peak prevalence in DEB in
      adolescence and young adult age is demonstrated. Conclusions: The results of this
      study point to the need for increased awareness of psychological comorbidity
      among adults with type 1 diabetes, in particular young adult females. Screening
      is recommended to secure early detection and subsequent intervention for these
      individuals.

PMID- 30214806
TI  - Treatment of Darier's disease with oral magnesium: a case report.
AB  - Darier's disease, an autosomal dominant genodermatosis, arises from a mutation in
      the ATP2A2 gene that codes for sarco/endoplasmic reticulum Ca2+-ATPase in the
      endoplasmic reticulum and is characterized by greasy keratotic papules commonly
      found in seborrheic regions. Conventional treatments, including topical
      corticosteroids, antibiotics, antifungals and retinoids, often have limited
      efficacy. The present article reports the novel use of oral magnesium chloride
      supplementation (300 mg daily) in the treatment of Darier disease. After 5 years
      of limited improvement using conventional therapies, significant improvements in
      neck lesions were observed within 1 month of starting oral magnesium chloride.
      This suggests that oral magnesium chloride may be an effective therapeutic option
      for Darier disease, although further in vitro and clinical trials are necessary
      to evaluate its clinical efficacy.

PMID- 30214807
TI  - A case report of bosutinib-induced interstitial granulomatous drug reaction in a
      patient with chronic myelogenous leukemia: a case report.
AB  - Bosutinib is a BCR-ABL tyrosine kinase inhibitor approved for the treatment of
      Philadelphia chromosome-positive chronic myelogenous leukemia. We report a case
      of bosutinib-induced interstitial granulomatous drug reaction in a 50-year-old
      Caucasian female with chronic myelogenous leukemia. Histologic analysis of a
      punch biopsy showed diffuse interstitial granulomatous infiltrates consisting of
      histiocytes amid thickened collagen accompanied by eosinophils. Her lesions
      improved with clobetasol 0.05% cream. No cases describing BCR-ABL tyrosine kinase
      inhibitor-associated interstitial granulomatous drug reaction were found in a
      search of the literature. It is important for physicians to be aware of the risk
      of interstitial granulomatous drug reaction associated with bosutinib treatment.

PMID- 30214808
TI  - Unusual presentation of a cutaneous metastasis in the face arising from gastric
      cancer: a case report.
AB  - A well-known example of gastrointestinal cancers metastasizing to the skin is
      Sister Mary Joseph's nodule, which usually presents as a cutaneous nodule on the
      umbilicus. In this case, a 91-year-old man was referred to our dermatology clinic
      for a rapidly growing 3 cm * 2 cm ulcerative nodule at his chin. Biopsy showed
      skin metastasis originating from a gastric adenocarcinoma. The subcutaneous and
      cutaneous manifestation of gastric cancer is very rare and associated with a poor
      prognosis and widespread metastatic disease as presented in this case. However,
      skin metastasis may be the first clinically apparent sign of underlying systemic
      malignancy and therefore immediate clarification in case of uncertainty is
      recommended.

PMID- 30214809
TI  - Treating electroconvulsive therapy-induced mania with more electroconvulsive
      therapy: Evidence for electroconvulsive therapy as the ultra-mood stabilizer.
AB  - Electroconvulsive therapy has been described as a mood stabilizer, as it is
      effective in all stages of bipolar disorder. Electroconvulsive therapy-induced
      mania is a known and potentially dangerous risk of treating bipolar depression
      with electroconvulsive therapy and there are no established guidelines for the
      management of electroconvulsive therapy-induced mania. We report a case of
      electroconvulsive therapy-induced mania where electroconvulsive therapy was
      continued as the sole, effective antimanic agent, which is the first described
      case in literature.

PMID- 30214810
TI  - A fatal case of Ortner's syndrome and dysphagia aortica secondary to rapidly
      expanding mycotic thoracic aortic aneurysm in a chronic kidney disease patient.
AB  - Ortner's syndrome or cardiovocal syndrome is a rare condition and refers to the
      association between cardiovascular conditions, usually cardiac enlargement from
      mitral stenosis, and recurrent laryngeal nerve palsy. We reported an interesting
      case of a patient with end-stage renal disease on regular dialysis who developed
      both Ortner's syndrome and dysphagia aortica as a result of an aortic arch
      aneurysm. The aneurysm underwent a rapid increase in size, likely as a result of
      Staphylococcus aureus infection (mycotic aneurysm) from an internal jugular
      dialysis catheter. This case highlighted the importance of cardiovascular
      conditions as rarer causes of dysphonia and dysphagia, particularly with the
      existence of an extrinsic infective source.

PMID- 30214811
TI  - Late presentation of Torsades de Pointes related to fluoxetine following a
      multiple drug overdose.
AB  - Background: Fluoxetine is a selective serotonin reuptake inhibitor (SSRI)
      commonly used in the treatment of depression. While most intoxications with
      SSRI's have favorable outcomes and do not require interventions other than strict
      observation of vital signs and heart rhythm, clinicians should be aware of the
      life-threatening complications that may occur. Case presentation: A 61-year-old
      woman presented to the emergency department after an intentional multiple drug
      overdose. Upon examination, she was somnolent with stable respiration and
      hemodynamics. Electrocardiography showed a prolonged QTc interval of 503 ms. The
      patient was admitted to the ICU for cardiopulmonary monitoring. During admission,
      the patient remained stable and showed improved neurologic function over time.
      After 22 h, a second ECG showed normalization of the QTc interval to 458 ms.
      However, 36 to 40 h after admission, our patient developed recurrent episodes of
      Torsades de Pointes (TdP) with loss of cardiac output, leading to cardiopulmonary
      resuscitation. Spontaneous circulation was restored after intravenous
      administration of magnesium sulphate. Retrospective serum analysis revealed
      fluoxetine concentrations of 2700 mcg/l. Conclusion: Most intoxications with
      selective serotonin reuptake inhibitors (SSRI) have favorable outcomes and do not
      require medical interventions other than strict cardiopulmonary observation.
      However, higher doses have been associated with QTc interval prolongation, TdP,
      serotonin syndrome, and death. This case illustrates that life-threatening
      complications may occur late in the course of hospital admission. Even though
      overdoses with SSRI's generally result in few fatalities, clinicians should be
      aware of the life-threatening clinical manifestations that may occur. Despite
      being an imperfect predictor of imminent TdP, continuous monitoring of cardiac
      rhythm is strongly recommended when either cardiac or non-cardiac symptoms are
      present.

PMID- 30214813
TI  - Elevated 4beta-hydroxycholesterol/cholesterol ratio in anorexia nervosa patients.
AB  - Recent studies have shown that the cytochrome P450 (CYP) 3A phenotype marker
      4beta-hydroxycholesterol/cholesterol (4betaOHC/C) ratio is negatively correlated
      with body weight in healthy volunteers, and that obese patients have lower
      4betaOHC levels than healthy controls. However, 4betaOHC/C ratio in underweight
      patients has yet to be reported. The aim of this study was to examine potential
      differences in CYP3A activity between underweight patients with anorexia nervosa
      and normal-weight volunteers by measuring plasma 4betaOHC/C ratio. Furthermore,
      we wished to describe any association between body mass index (BMI) and
      4betaOHC/C ratio in underweight patients. A total of 20 underweight patients and
      16 normal-weight volunteers were included in the study, all females. Underweight
      patients had a median 4betaOHC/C ratio (molar ratio * 10-5) of 2.52 (range, 0.90
      11.3) compared to 1.29 (0.56-2.09) in normal-weight subjects (Mann-Whitney P =
      0.0005). 4betaOHC/C ratio was negatively correlated with BMI in underweight
      patients (r = -0.56, P = 0.011), and in the whole study population (r = -0.67, P
      < 0.0001). This suggests that the negative correlation between 4betaOHC/C and
      BMI, which has previously been reported between 4betaOHC/C and body weight in
      healthy volunteers, extends to underweight patients. The findings indicate that
      CYP3A activity increases with decreasing BMI, resulting in higher CYP3A activity
      in underweight patients compared to normal-weight subjects. The potential
      clinical relevance of this needs to be studied further by comparing
      pharmacokinetics of drugs subjected to CYP3A-mediated metabolism in underweight
      vs. normal-weight individuals.

PMID- 30214812
TI  - Hepcidin predicts response to IV iron therapy in patients admitted to the
      intensive care unit: a nested cohort study.
AB  - Background: Both anaemia and red blood cell (RBC) transfusion are common and
      associated with adverse outcomes in patients admitted to the intensive care unit
      (ICU). The aim of this study was to determine whether serum hepcidin
      concentration, measured early after ICU admission in patients with anaemia, could
      identify a group in whom intravenous (IV) iron therapy decreased the subsequent
      RBC transfusion requirement. Methods: We conducted a prospective observational
      study nested within a multicenter randomized controlled trial (RCT) of IV iron
      versus placebo. The study was conducted in the ICUs of four tertiary hospitals in
      Perth, Western Australia. Critically ill patients with haemoglobin (Hb) of < 100
      g/L and within 48 h of admission to the ICU were eligible for participation after
      enrolment in the IRONMAN RCT. The response to IV iron therapy compared with
      placebo was assessed according to tertile of hepcidin concentration. Results:
      Hepcidin concentration was measured within 48 h of ICU admission in 133 patients.
      For patients in the lower two tertiles of hepcidin concentration (< 53.0 MUg), IV
      iron therapy compared with placebo was associated with a significant decrease in
      RBC transfusion requirement [risk ratio 0.48 (95% CI 0.26-0.85), p = 0.013].
      Conclusions: In critically ill patients with anaemia admitted to an ICU, baseline
      hepcidin concentration predicts RBC transfusion requirement and is able to
      identify a group of patients in whom IV iron compared with placebo is associated
      with a significant decrease in RBC transfusion requirement. Trial registration:
      Australian New Zealand Clinical Trials Registry: ANZCTRN12612001249 Registered
      26/11/2012.

PMID- 30214814
TI  - Country ownership and sustainability of Nigeria's HIV/AIDS Supply Chain System:
      qualitative perceptions of progress, challenges and prospects.
AB  - Background: The emergency response phase to HIV epidemic in Nigeria and other
      countries saw to the deployment of donors' resources with little consideration
      for country ownership (CO) and sustainability. The progress that has been made in
      the fight against the pandemic has however precipitated a paradigm shift towards
      CO and sustainability. With the decline in donors' funding, countries must
      continually evaluate their readiness to own and sustain their HIV response
      especially the supply chain system (SCS) and bridge any observed gaps. This study
      assessed the current understanding of CO and sustainability of Nigeria's HIV/AIDS
      SCS, established progress that has been made, identified challenges that may be
      hampering CO and possible recommendations to address these challenges. It also
      explored opportunities that the country can leverage on. Methods: We conducted a
      cross sectional descriptive study through semi-structured interview of twelve
      purposefully selected key informants involved in HIV/AIDS supply chain
      management. Transcribed qualitative data were analyzed using a thematic approach.
      Results: Among other submissions, respondents acknowledged that CO involves non
      government stakeholders. Key CO and sustainability achievements were: development
      of national strategic plans and policy documents, establishment of coordinating
      structures, allocation of funds for some logistics activities at the state level
      and payment of salaries of government staff, institution of pre-service training,
      use of logistics data for decision making and the unification of the hitherto
      parallel HIV/AIDS supply chains. Challenges included: inadequate domestic
      funding, bureaucratic bottlenecks and inadequate manpower at the health facility
      level. Respondents recommended more political commitment and increased government
      funding, exploration of alternative sources of funding, improved accountability,
      effective healthcare workforce planning and local manufacture of HIV commodities.
      Existing structures and programmes that the country can leverage on included:
      Nigeria Supply Chain Integration Project, National Health Insurance Scheme and
      the private sector. Conclusions: Nigeria has made some progress towards achieving
      CO and sustainability. The country however needs to address financial and human
      resource gaps through innovative resource mobilization and effective workforce
      planning. As other countries plan for CO and sustainability, it is important to
      secure political buy-in and adopt a working definition for CO and sustainability
      while resource mobilization and workforce planning should be prioritized.

PMID- 30214815
TI  - Treatment fidelity in the Camden Weight Loss (CAMWEL) intervention assessed from
      recordings of advisor-participant consultations.
AB  - Background: Variations in the delivery of content and process can alter the
      effectiveness of complex interventions. This study examined the fidelity of a
      weight loss intervention (Camden Weight Loss) from recorded consultations by
      assessing advisors' delivery of content, use of motivational interviewing
      approach and therapeutic alliance. Methods: A process evaluation was conducted of
      advisor-participant consultations in a 12-month randomised controlled trial of an
      intervention for adult volunteers with a body mass index categorised as
      overweight or obese. A convenience sample of 22 consultations (12% of 191
      participants) recorded at the intervention mid-point were available for analysis.
      Consultations were independently rated by two observers independent of
      intervention or study delivery, using: a fidelity scale, the Motivational
      Interviewing Treatment Integrity Scale and the Primary Care Therapy Process
      Rating Scale. Raters were blind to participants' responses to the intervention
      and weight outcomes. Half the participants (N = 11) achieved significant weight
      loss (>= 5% of baseline weight). Results: A mean of 41% of prescribed content was
      delivered, with a range covered per session of 8-98%, falling below the 100%
      content expected per session. Tasks included most frequently were: taking weight
      and waist measurements (98%), scheduling next appointment (86%), review of
      general progress (85%) and reviewing weight change (84%). Individual items most
      frequently addressed were 'giving encouragement' and 'showing appreciation of
      participant's efforts' (95 and 88% respectively). Consultation length (mean 19
      min, range 9-30) was shorter than the 30-min allocation. Quantity of content
      correlated with consultation length (p < 0.01). Advisors' use of motivational
      interviewing was rated at 'beginner proficiency' for Global Clinician Rating,
      Reflection to Question Ratio and Percent Open Questions. Therapeutic alliance
      scores were moderate. Affective aspects were rated highly (e.g. supportive
      encouragement, involvement and warmth). Conclusions: Intervention fidelity varied
      in both content and process, emphasising the importance of ongoing fidelity
      checks in a complex intervention. Advisors focused on certain practical aspects
      of the intervention and providing an encouraging interpersonal climate. This
      concurs with other research findings, which have revealed the value participants
      in a weight loss intervention place on an empathic advisor-participant
      relationship. Clinical trials registration: Registered with Clinicaltrials.gov,
      number NCT00891943, on 1 May 2009.

PMID- 30214816
TI  - Variation of the PR interval for confirming ventricular pre-excitation on a 12
      lead ECG.
AB  - We present the case of a 14-year-old female patient with recurrent episodes of
      paroxysmal supraventricular tachycardia (PSVT). Her ECG showed a PR interval of
      160 ms in lead II, and a delta wave pattern in leads V2 and V3, with a normal QRS
      interval of 100 ms. We analyzed the three criteria for confirmation of minimal
      pre-excitation: (i) absence of a Q wave in V6; (ii) presence of an R wave in V1
      and (iii) absence of an R wave in avR. The 3 criteria were not met and failed to
      establish a diagnosis of ventricular pre-excitation. The electrophysiological
      study confirmed the presence of a left accessory pathway. A new criterion was
      analyzed: the variation of the PR interval on the same ECG. A difference of >30
      ms was successful to confirm the presence of an accessory pathway before ablation
      and its absence after catheter ablation.

PMID- 30214817
TI  - Ventricular pre-excitation using a 12-lead ECG: a challenging diagnosis.

PMID- 30214818
TI  - Undernutrition and its association with socio-demographic, anemia and intestinal
      parasitic infection among pregnant women attending antenatal care at the
      University of Gondar Hospital, Northwest Ethiopia.
AB  - Background: Under nutrition is a worldwide public health problem affecting the
      well-being of millions of pregnant women in the developing world. Only limited
      research has been conducted on the prevalence and determinants of maternal
      nutritional status in Ethiopia. Particularly, data on the nutritional status of
      pregnant women are lacking. The aim of this study was to assess the prevalence
      and determinants of undernutrition among pregnant women attending antenatal care
      at the University of Gondar Hospital, Northwest Ethiopia. Methods: An institution
      based cross-sectional study was conducted in January and February 2016. Randomly
      selected 409 pregnant women were included in the study. Nutritional status was
      estimated using mid-upper-arm circumference. Data on potential determinants of
      undernutrition were gathered using a structured questionnaire. The blood sample
      was collected to analyze hemoglobin. The stool sample was collected to identify
      intestinal parasitic infections. Statistical analysis was done using logistic
      regression. P-value < 0.05 at 95% confidence interval was considered as
      statistically significant. Results: The prevalence of undernutrition among
      pregnant women was 16.2% (95% CI: 12.4-20.1%). Using a logistic regression model,
      factors significantly associated with the undernutrition were living in rural
      areas (AOR = 2.26), low educational status [no formal education (AOR = 2.91),
      primary education (AOR = 2.69)], history of too many births (AOR = 2.55), anemia
      (AOR = 2.01), and intestinal parasitic infection (AOR = 2.73). Conclusion: The
      study findings provide evidence for the public health significance of under
      nutrition among pregnant women in the study area. The problem must be combated
      through rural livelihood promotion, socioeconomic empowerment of women, sustained
      nutrition education and expansion of family-planning services in the area.

PMID- 30214819
TI  - Utility and effectiveness of Symbicort(r) Turbuhaler(r) (oral inhalation
      containing budesonide and formoterol) in a patient with severe asthma after
      permanent tracheostomy.
AB  - Background: The utility and effectiveness of inhalational asthma therapy in
      patients with a permanent tracheostomy has not been established. Previously, a
      few studies reported the use of nebulizer-type inhalers for treating these
      patients. Symbicort(r) Turbuhaler(r) (Symbicort) is an orally inhaled dry powder
      containing the corticosteroid budesonide and the bronchodilator formoterol. There
      are no reports describing the successful use of Symbicort in patients with a
      permanent tracheostomy. Case presentation: We describe the case of a woman with
      poorly controlled severe asthma after a permanent tracheostomy. She had developed
      thyroid cancer with tracheal invasion for which right thyroid lobectomy and
      tracheal and esophageal resection were performed, with subsequent construction of
      a permanent tracheostomy. In our case, prior to surgery, asthma control had been
      improved by adding a bronchodilator-the long-acting muscarinic antagonist
      tiotropium-and the anti-IgE antibody agent omalizumab to single maintenance and
      reliever therapy (SMART) using Symbicort; surgery was then performed. After
      surgery, asthma control worsened as a result of a change from Symbicort to
      budesonide nebulizer and a tulobuterol patch. In order to resume SMART therapy,
      an In-Check(r) inspiratory flow meter was used to measure and assess whether the
      inspiratory flow rate was sufficient for a dry-powder inhaler. Inhalation
      guidance was provided. On inhalation with the tracheostomy closed at the same
      time, the inspiratory flow rate was 43 L/min at the maximum. This was judged to
      be sufficient for the effect of Symbicort, and thus the inhaler was changed to
      Symbicort. Asthma symptoms promptly improved, and the patient was subsequently
      discharged. Conclusions: The use of Symbicort resulted in improved asthma control
      in a patient with severe asthma following a permanent tracheostomy. Thus, it is
      suggested that inhalation powder could be an option for patients with permanent
      tracheostomy.

PMID- 30214820
TI  - Safety profile of prophylactic rescue dosing of immediate-release oral opioids in
      cancer patients.
AB  - Background: Appropriate prophylactic rescue dosing of opioids is considered
      effective for cancer pain relief, but no study has reported the safety of such
      prophylactic rescue. We compared the safety of prophylactic rescue dosing of
      immediate-release oral opioids with that of regular rescue dosing. Methods: The
      study included 103 cancer patients who used either immediate-release morphine
      syrup or immediate-release oxycodone powder at Shizuoka Cancer Center between
      January and December 2016. Patients were divided into those who mostly used
      (prophylactic group) and those who never used (regular group) prophylactic rescue
      doses of opioids and compared the incidence of adverse events (AEs). We also
      investigated whether the prophylactic rescue dose negatively interfered with its
      objective activity, such as meals. Results: Incidence of each AE in the
      prophylactic versus regular groups was as follows: somnolence, 20.6% versus
      14.3%; nausea, 22.1% versus 17.1%; constipation, 19.1% versus 20.0%; urinary
      retention, 1.5% versus 2.9%; delirium, 4.4% versus 8.6%; and pruritus, 0% versus
      2.9%. No serious AE associated with prophylactic rescue dosing was observed. No
      significant difference was observed in the incidence of any AE between the two
      groups (p > 0.05, Fisher's exact test). No AE interfered with the objective
      activity of the prophylactic rescue dose. Conclusion: Incidence of AEs associated
      with prophylactic rescue dosing is not different from that associated with
      regular rescue dosing. In addition, the prophylactic rescue dose did not
      adversely affect its objective activity, suggesting the safety of appropriate
      prophylactic rescue dosing was similar to that of regular rescue dosing. Trial
      registration: The study approval number in the institution; H29-J30-29-1-3.
      Registered June 5, 2017.

PMID- 30214821
TI  - Oral prednisolone for acute otitis media in children: protocol of a pilot
      randomised, open-label, controlled study (OPAL study).
AB  - Background: Acute otitis media (AOM) is an acute inflammation of the middle ear
      commonly found in children, for which antibiotics are frequently prescribed.
      However, antibiotics are beneficial for only one third of AOM cases, and then,
      with only modest benefit. Since antibiotic use leads to risk of side effects and
      resistance, effective alternative treatments are required. Corticosteroids are a
      candidate because of their anti-inflammatory effects, although evidence of their
      efficacy and harms is insufficient. Accordingly, we plan a large, rigorous
      clinical trial to test this. Initially, we will test pre-specified methods and
      procedures (including the overall process, resources, management, and scientific
      components) in a pilot study of corticosteroids for AOM, which will inform a
      future, definitive trial. Methods: This is a pilot pragmatic, randomised, open
      label, single-blind, controlled study of corticosteroids as either monotherapy or
      an addition to antibiotics in 60 children aged 6 months to 12 years with AOM in
      two cities (Jakarta and Bekasi) in Indonesia. We will randomise eligible children
      to prednisolone or control. We will also stratify by disease severity and
      randomise those with mild AOM to expectant observation plus prednisolone or
      observation alone and those with severe AOM to prednisolone plus antibiotic or
      antibiotic alone. Our outcomes are to determine (1) recruitment rates, (2) the
      success of the study procedures, (3) the ability to measure planned outcomes of
      the proposed main study, (4) the compliance to study visits and study medication,
      and (5) verification of the sample size calculation for the main study. We will
      also assess middle ear effusion using tympanometry as part of a mechanistic sub
      study. Discussion: This study will test all procedures in preparation for the
      main study, including several potential obstacles and challenges from the
      perspective of participating physicians, nurses, pharmacists, and the parents of
      eligible children. This information will be useful for developing strategies to
      overcome practical and procedural issues. This study may also provide information
      about the effects of corticosteroids on middle ear effusion in AOM. Trial
      registration: Study registry number: ACTRN12618000049279. Name of registry: the
      Australian New Zealand Clinical Trials Registry (ANZCTR). Date of registration:
      16 January 2018.

PMID- 30214823
TI  - Developing the infrastructure for patient review in academic journals.
AB  - Plain English summary: Peer review is a well-established part of academic
      publishing. Its function is to assess the quality of a manuscript before
      publication in a journal. Research involvement and Engagement is the world's
      first co-produced journal dedicated to developing the evidence base of patient
      and public involvement and engagement in health and social care research.
      Alongside traditional academic peer review we also involve other key
      stakeholders, including patients, carers, the public, policy makers, funders and
      practitioners. Following a recent survey looking at the motivations and feedback
      from patient reviewers in academic journals, we consider the key findings,
      reflect on what we already do and based on the feedback from the survey, we
      outline plans for future development. These plans include improving training and
      guidance for reviewers, changes to systems and workflows, acknowledging and
      engaging reviewers, and building a sense of community. Abstract: Peer review is a
      well-established part of academic publishing. Its function is to assess the
      quality of a manuscript before publication in a journal. Research involvement and
      Engagement is the world's first co-produced journal dedicated to developing the
      evidence base of patient and public involvement and engagement in health and
      social care research. Alongside traditional academic peer review we also involve
      other key stakeholders, including patients, carers, the public, policy makers,
      funders and practitioners. Following a recent survey looking at the motivations
      and feedback from patient reviewers in academic journals, we consider the key
      findings, reflect on what we already do and based on the feedback from the
      survey, we outline plans for future development. These plans include including
      improving training and guidance for reviewers, changes to systems and workflows,
      acknowledging and engaging reviewers, and building a sense of community.

PMID- 30214822
TI  - Models and frameworks of patient engagement in health services research: a
      scoping review protocol.
AB  - Plain English summary: Patient engagement in research is an emerging approach
      that involves active and meaningful collaboration between researchers and
      patients throughout all phases of a project, including planning, data collection
      and analysis, and sharing of findings. To better understand the core features
      (elements) that underlie patient engagement, it is useful to have a look at
      models and frameworks that guide its conduct. Therefore, this manuscript aims to
      present a protocol for a scoping review of models and frameworks of patient
      engagement in health services research. Methods: Our protocol design is based on
      an established framework for conducting scoping reviews. We will identify
      relevant models and frameworks through systematic searches of electronic
      databases, websites, reference lists of included articles, and correspondence
      with colleagues and experts. We will include published and unpublished articles
      that present models and frameworks of patient engagement in health services
      research and exclude those not in English or unavailable as full texts. Two
      reviewers will independently review abstracts and full texts of identified
      articles for inclusion and extract relevant data; a third reviewer will resolve
      discrepancies. Our primary objective is to count and describe elements of patient
      engagement that overlap (present in 2 or more) and diverge among included models
      and frameworks. Discussion: We hope this review will raise awareness of existing
      models and frameworks of patient engagement in health services research. Further,
      by identifying elements that overlap and diverge between models and frameworks,
      this review will contribute to a clearer understanding of what patient engagement
      in research is and/or could be. Abstract: Background: Patients can bring an
      expert voice to healthcare research through their lived experience of receiving
      healthcare services. Patient engagement in research is an emerging approach that
      challenges researchers to acknowledge and utilize this expertise through
      meaningful and active collaboration with patients throughout the research
      process. In order to facilitate a clearer understanding of the core elements that
      underlie patient engagement, it is useful to examine existing models and
      frameworks that guide its conduct. Therefore, the aim of this manuscript is to
      present a protocol for a scoping review of models and frameworks of patient
      engagement in health services research. Methods: Drawing on Arksey and O'Malley's
      and Levac et al.'s framework for scoping reviews, we designed our protocol to
      identify relevant a) published articles through systematic searches of 7
      electronic databases and snowball sampling and b) unpublished articles through
      systematic searches of databases and websites and snowball sampling. We will
      include published and unpublished models and frameworks of patient engagement in
      health services research and exclude those not in English or unavailable as full
      texts. Two reviewers will independently screen the abstracts and full texts of
      identified articles for inclusion and extract relevant data; a third reviewer
      will resolve disagreements. We will conduct a descriptive analysis of the
      characteristics (i.e., elements underlying patient engagement and those related
      to the study authors, publication, and model/framework) of included articles and
      a narrative analysis of the data concerning elements of the model or framework.
      Our primary objective is to count and describe elements of patient engagement
      that overlap (present in >= 2) and diverge (present in < 2) among identified
      models and frameworks. Discussion: Through identification of elements that
      overlap and diverge between existing models and frameworks, this review will
      provide a starting point for the critical reflection on our collective
      understanding of what patient engagement in health services research is and/or
      could be. Ultimately, we hope that the findings of this review raise awareness of
      existing models and frameworks and shed light on some of the complexity of
      conducting patient engaged research through identification of key elements that
      shape this approach.

PMID- 30214824
TI  - Proteomics and melanoma: a current perspective.
AB  - Proteomics is the study of the protein complement of the genome, and this
      powerful technique complements genomic studies. Proteomic experiments result in
      the generation of large volumes of data requiring complicated analysis algorithms
      and subsequent confirmatory studies. Until recently, technological limitations of
      experimental protocols precluded the use of formalin-fixed tissues for these
      types of studies. Recent advances have allowed the use of valuable archived
      patient tissue samples in proteomic research, resulting in an opportunity to
      perform cutting edge translational research. The field of melanoma research
      stands to benefit greatly from collaboration between dermatopathologists and
      proteomic scientists. This article seeks to: 1) describe proteomics for
      dermatologists and pathologists, including the tools used in proteomic research,
      and 2) convey a historical account of proteomic studies within the field of
      melanoma followed by a discussion on how recent advances are informing current
      studies.

PMID- 30214825
TI  - Change in subfoveal choroidal thickness in diabetes and in various grades of
      diabetic retinopathy.
AB  - Background: To evaluate subfoveal choroidal thickness (SFCT) change in diabetes
      and in various grades of diabetic retinopathy (DR) in comparison to age-matched
      healthy subjects. Methods: This prospective observational study included 100 eyes
      of diabetic patients without DR (group D), 100 eyes with DR (group R), and 100
      eyes of healthy subjects (group N). The assessment included demographics,
      duration of diabetes, comprehensive ocular examination, fundus photography
      with/without fundus fluorescein angiography, spectral domain optical coherence
      tomography with enhanced depth imaging to assess SFCT. Results: The SFCT was
      comparable between groups N (310.65 +/- 37.34 um) and D (308.48 +/- 30.06 um; P =
      0.60), but was significantly lower in R (296.52 +/- 21.41 um; P < 0.01). The SFCT
      was significantly lower in proliferative DR (n = 36; SFCT = 284.56 +/- 21.09 um)
      as compared to non-proliferative DR (n = 64; SFCT = 303.25 +/- 18.59 um; P <
      0.001). The SFCT had moderately negative correlation with severity of DR (R = -
      0.50; P < 0.01). The difference in SFCT when compared with normal subjects was
      significant only in severe/very severe non-proliferative DR (294.47 +/- 15.65 um;
      P < 0.01) and in proliferative DR (284.56 +/- 21.09 um; P < 0.01). There was a
      negative correlation of SFCT with the duration of diabetes (R = - 0.41; P <
      0.01). Conclusion: SFCT decreases with increasing duration of diabetes. The
      decrease is significant after the onset of severe DR, and is proportionate to the
      severity of DR.

PMID- 30214826
TI  - Epstein - Barr virus Infection in a Patient with Neuromyelitis Optica Spectrum
      Disorder and Sjogren's Syndrome: A Case Report and Review of Literature.
AB  - Background: The association of Neuromyelitis Optica Spectrum Disorders (NMOSD)
      with autoimmune disorders including Sjogren's syndrome (SS), is well recognized.
      Epstein Barr virus (EBV) has been associated to various neurological entities. We
      describe a case where EBV infection likely preceded NMOSD in a patient with
      unrecognized SS. The clinical features, work up and management are described.
      Case presentation: A 40-year woman with history of stroke and Guillain-Barre
      Syndrome (GBS) two years prior, presented with progressive lower extremity
      weakness and pain. Brain MRI revealed hyperintensities in the cerebellar and
      parietal lobes consistent with old infarcts, high intensity signal in the white
      matter and enhancing intramedullary lesion at the level of T2 and the conus
      medullaris. Cerebrospinal fluid (CSF) revealed no oligoclonal bands. Next day,
      the patient developed right ankle weakness and urinary incontinence. NMOSD was
      suspected and pulse steroids initiated. Patient's weakness resolved. Antinuclear
      antibodies (ANA), anti-SSA/SSB and Aquaporin 4 antibodies (AQP4Ab) were positive.
      CSF was positive for EBV. Parotid gland ultrasound revealed non-homogeneous
      tissue.Ganciclovir and plasmapheresis were started. The patient's sensation and
      motor deficits improved and one month after, she had regained motor power and
      sphincter control. The patient was discharged on oral prednisone and plans for
      rituximab infusions.On follow-up imaging, Spinal MRI showed areas of myelomalacia
      and complete resolution at the level of T2 and conus medularis lesions
      respectively. The patient had no additional flares, but did complain of chronic
      neuropathic pain. Conclusion: NMOSD commonly coexist with other autoimmune
      diseases. The association of SS and NMOSD is well recognized. EBV infections can
      present with neurological manifestations however, EBV has also been linked to the
      development of autoimmunity. In our case, EBV was detected in CSF and antiviral
      therapy was initiated in addition to the treatment modalities for NMOSD which led
      to a full recovery in our patient.

PMID- 30214827
TI  - Barriers to HIV service utilisation by people living with HIV in two provinces of
      Zimbabwe: Results from 2016 baseline assessment.
AB  - Background: The emergence of antiretroviral therapy (ART) transformed HIV from a
      terminal illness to a chronic disease. However, limited access to health services
      remains one of many barriers to HIV service utilisation by people living with HIV
      (PLHIV) in low-resource settings. The goal of this study was to describe the
      barriers to HIV service utilisation in two provinces of Zimbabwe. Methods: A
      qualitative descriptive study was conducted with PLHIV and village health workers
      (VHW) in eight districts within the two provinces. Convenience sampling was used
      to select the participants. This sampling was limited to communities supported by
      health facilities with more than 500 PLHIV enrolled into HIV care and treatment.
      Interviews were audio-recorded and transcripts were subjected to thematic content
      analysis. Results: A total of 22 community focus group discussions (FGDs) were
      conducted. Barriers to using HIV services cited in PLHIV and VHW FGDs were
      similar. These were categorised as health system-related barriers, which include
      user fees, long waiting times, lack of confidentiality and negative attitudes by
      healthcare providers, and lack of consistent community-based HIV services.
      Community-related barriers cited were stigma and discrimination, food insecurity,
      distance to facilities and counterproductive messaging from religious sectors.
      Client-related factors reported were inadequate male involvement in HIV-related
      activities and defaulting after symptoms improved. Conclusion: Our assessment has
      indicated that there are several barriers to the utilisation of HIV services by
      PLHIV in the two provinces of Zimbabwe. As new strategies and programmes are
      being introduced in the current resource-constrained era, efforts should be made
      to understand the needs of the clients. If programmes are designed with an effort
      to address some of these challenges, there is a possibility that countries will
      quickly achieve the 90-90-90 targets set by The Joint United Nations Programme on
      HIV/AIDS.

PMID- 30214829
TI  - Earthquake in Western Iran: Renovation Kills.
AB  - INTRODUCTION: Earthquake is the most important cause of death from natural
      disasters in Iran. This paper brings attention to the main causes of loss of life
      due to the Kermanshah province earthquake (Nov 12 2017), and provides a wakeup
      call about the unsafe nature of buildings there. METHODS: This study is based on
      official reports review and a field assessment in the areas affected by the
      earthquake in western Iran. RESULTS: Although buildings in this area are mainly
      old structures, strangely, more than 70% of the destroyed buildings in this
      earthquake were under 5 years of age, newly built or renovated buildings
      according to mandated building codes. DISCUSSION: Mandated building codes and
      construction rules and regulations are not respected even for the newly
      constructed or reconstructed structures buildings.

PMID- 30214828
TI  - Mortality After Complex Displaced Proximal Humerus Fractures in Elderly Patients:
      Conservative Versus Operative Treatment With Reverse Total Shoulder Arthroplasty.
AB  - Introduction: Proximal humerus fractures (PHFs) are a common fragility fracture
      and have been shown to increase mortality in elderly patients. In the last
      decade, reverse total shoulder arthroplasty (RTSA) was introduced as a reliable
      operative treatment option for this indication. In other fragility fractures,
      most notably hip fractures, urgent surgical treatment can reduce mortality. The
      purpose of this study is to evaluate whether treatment with RTSA can reduce 1
      year mortality in elderly patients with complex displaced PHFs. Materials and
      Methods: A retrospective study was performed to compare 1-year mortality between
      2 groups of elderly patients (>75 years old) who presented to a level 1 trauma
      center emergency department with complex displaced PHFs. The conservative
      treatment group (n = 83; mean age, 83.7 years) presented from 2008 to 2010 when
      RTSA was not yet available, and treatment was nonoperative. The surgical
      treatment group (n = 62; mean age, 82.2 years) presented from 2012 to 2015 and
      underwent RTSA. Results: One-year mortality was 8.1% (male 7.1%; female 8.3%) in
      the surgical treatment group and 10.8% (male 18.8%; female 9.0%) in the
      conservative treatment group. The reduction in mortality in the surgical
      treatment group was not significant (entire cohort P = .56; males P = .35;
      females P = .59). Discussion: Recent studies failed to show better functional
      results after surgical treatment with RTSA when compared to conservative
      treatment. This study suggests that a benefit of surgical treatment with RTSA
      that was not examined until now might exist-a reduction in the increased
      mortality risk associated with PHFs. Conclusions: There was no significant
      difference in 1-year mortality between the groups, although there was a trend
      showing lower mortality with RTSA, mostly in men. Further studies with larger
      populations and longer follow-up times are needed to determine whether this trend
      is of clinical significance.

PMID- 30214830
TI  - Tracing Back the Source of an Outbreak of Salmonella Typhimurium; National
      Outbreak Linked to the Consumption of Raw and Undercooked Beef Products, the
      Netherlands, October to December 2015.
AB  - INTRODUCTION: On 23 October 2015, six related cases with gastroenteritis called
      the Netherlands Food and Consumer Product Safety Authority. They suspected filet
      americain, a raw beef spread, to be the source of infection. Leftovers and stool
      samples tested positive for Salmonella Typhimurium. Multiple locus variable
      number of tandem repeat analysis (MLVA) revealed a MLVA pattern (02-23-08-08
      212), which had not been detected in the Netherlands before. Concomitantly, an
      increase of this MLVA type was observed in the national Salmonella surveillance,
      amounting to 46 cases between 26 October and 9 December. METHODS: To investigate
      whether filet americain or an alternative (related) source could  be linked to
      surveillance-reported cases, cases (n=38) were invited to complete a
      questionnaire and upstream source tracing to map the food supply chain was
      initiated. RESULTS: Rapid interdisciplinary action resulted in identification of
      a contaminated 46-ton batch of beef distributed via a Dutch deboning plant as the
      likely source of infection. In total, 24/29 respondents (83%) could be linked to
      the incriminated batch of beef products (predominantly filet americain and minced
      beef). DISCUSSION: Repeated identification of raw meat products as a source of
      infection emphasizes the importance of awareness of the risk of infection when
      handling or consuming these products. Improved measures and procedures on product
      labelling, pre-treatment or product testing should be considered.

PMID- 30214831
TI  - A cybernetic eye for rare disease.
AB  - Deep learning implemented in a collaborative cloud-based platform empowers
      ophthalmologists in the diagnosis of congenital cataracts.

PMID- 30214832
TI  - Is Usual Dietary Pattern Related to the Risk of Developing Breast Cancer?
AB  - Dietary patterns capture total diet providing a more comprehensive understanding
      of the effect of diet on chronic disease risk. Dietary patterns have been
      associated with several chronic diseases, including cardiovascular disease and
      selected cancers; however, the association with breast cancer remains unclear.
      The objective of this review was to examine critically the most recent literature
      on dietary patterns and breast cancer and report on current results, new
      developments, and future directions. Seven case-control and cohort studies from
      multiple countries have been published during the previous year (2011-2012). Many
      have analyzed a posteriori dietary patterns via factor and principal component
      analysis. Whereas results remain mixed, the majority of studies indicate
      healthier patterns decrease breast cancer risk, although patterns higher in meat
      and alcohol increase risk. Future studies that examine the associations between
      diet and tumor subtypes and collect dietary data at younger ages and, if
      possible, longitudinally would be beneficial.

PMID- 30214833
TI  - Criteria Definitions and Network Relations: The Importance of Criterion
      Thresholds.
AB  - Across various structured diagnostic instruments, the criteria used to diagnose
      alcohol use disorder (AUD) are not assessed consistently. For example, different
      instruments often pose questions that reflect different thresholds of the
      underlying symptoms. We consider the criteria for craving and the inability to
      cut down or stop drinking to demonstrate the influence of using different
      thresholds for a positive symptom endorsement with respect to the estimated edges
      of a symptom network. Results indicate that the utilization of these differing
      thresholds leads to significant differences in edge weights. Generally, higher
      thresholds relate more strongly to lower prevalence rate criteria, and the
      reverse for lower thresholds. These findings have implications for
      reproducibility of effects in symptom networks and their generalization across
      studies.

PMID- 30214834
TI  - SSR markers for Filago subg. Filago (Gnaphalieae: Asteraceae) and cross
      amplification in three other subgenera.
AB  - Premise of the Study: Microsatellite primers were developed for the first time in
      the genus Filago (Gnaphalieae: Asteraceae). These markers will facilitate low
      scale phylogenetic, phylogeographic, and population genetic studies within the
      genus Filago. Methods and Results: Ten pairs of polymorphic microsatellite
      primers (as well as five pairs of monomorphic primers) were identified and
      optimized on two species of Filago (F. gaditana and F. carpetana) using a
      microsatellite-enrichment library method and 454 GS-FLX technique. The
      polymorphic primers amplified tri- to hexanucleotide repeats and showed one to
      six alleles per locus for both species. Transferability was performed in 29
      samples corresponding to nine representative species of Filago. Conclusions: The
      results indicate the utility of the newly developed markers, which will be useful
      to delve into the phylogenetic relationships among the taxa within Filago. These
      microsatellites will enable studies of phylogeographic, reproductive, and genetic
      variation.

PMID- 30214835
TI  - Characterization of microsatellite markers for Moricandia moricandioides
      (Brassicaceae) and related species.
AB  - Premise of the Study: Polymorphic microsatellite markers were developed to study
      population structure and mating patterns of the monocarpic herb Moricandia
      moricandioides (Brassicaceae). Methods and Results: Illumina MiSeq sequencing was
      used to develop a panel of 15 polymorphic microsatellite markers that were tested
      across 77 individuals from three populations on the Iberian Peninsula. All
      markers were polymorphic in at least two studied populations, and the number of
      alleles ranged from one to 11 per locus. The levels of observed and expected
      heterozygosity ranged from 0.000 to 1.000 and from 0.153 to 0.865, respectively.
      Nine and 11 loci were successfully amplified in the congeneric species M.
      arvensis and M. foetida, respectively. Conclusions: The 15 microsatellite markers
      will be useful for population genetic studies of the genus Moricandia. These
      markers will serve as a useful tool for exploring population structure and mating
      patterns of M. moricandioides.

PMID- 30214836
TI  - Development of EST-SSR markers for Pluchea indica (Asteraceae) and cross
      amplification in related species.
AB  - Premise of the Study: Expressed sequence tag-simple sequence repeat (EST-SSR)
      markers were developed for Pluchea indica, a traditional medicinal species
      widespread along the tropical coastlines of Asia and northern Australia. Methods
      and Results: Based on transcriptome data for P. indica, a total of 40 primer
      pairs were initially designed and tested, of which 17 were successfully amplified
      and showed clear polymorphism. For these SSR loci, one to nine alleles per locus
      were identified. The levels of observed and expected heterozygosity ranged from 0
      to 0.9 and 0 to 0.831, respectively. Furthermore, 16, 17, and 12 loci were
      successfully amplified in three congeneric species, P. eupatorioides, P.
      pteropoda, and P. sagittalis, respectively. Conclusions: The SSR markers
      described here may be useful for further investigation of the population genetics
      of P. indica and related species.

PMID- 30214837
TI  - Evaluation of six regions for their potential as DNA barcodes in epiphyllous
      liverworts from Thailand.
AB  - Premise of the Study: Studies on the diversity of epiphyllous bryophytes have
      been limited because of minute and incomplete specimens and a lack of taxonomic
      expertise. The recent development of the DNA barcoding approach has allowed taxon
      identification and species discovery of many obscure groups of organisms.
      Methods: With DNA extractions from 99 samples of 16 species, we compared the
      efficiencies of six DNA markers (rbcL, matK, trnL-F, psbA, ITS1, and ITS2) in
      their ability to amplify, using a standard set of primers, as well as their
      discriminatory power, using distance-based and tree-based approaches with
      nucleotide data. Results: The amplification success was relatively high (70-90%)
      with all of the markers, except for matK, which yielded no success. The barcoding
      gap, as calculated from the difference between inter- and intraspecific genetic
      distances, was the highest in ITS2, whereas the highest numbers of monophyletic
      groups were found with ITS2 and rbcL. Discussion: rbcL should be used as a main
      barcoding marker with the addition of ITS2 for epiphyllous species. The
      development of DNA barcoding as a tool for quantifying species diversity will
      provide a rapid and reliable identification tool for epiphyllous bryophytes.

PMID- 30214838
TI  - Isolation and characterization of SSR and EST-SSR loci in Chamaecyparis
      formosensis (Cupressaceae).
AB  - Premise of the Study: Simple sequence repeat (SSR) and expressed sequence tag
      (EST)-SSR markers were developed as tools for marker-assisted selection of
      Chamaecyparis formosensis and for the molecular differentiation of cypress
      species. Methods and Results: Based on the SSR-enriched genomic libraries and
      transcriptome data of C. formosensis, 300 primer pairs were selected for initial
      confirmation, of which 19 polymorphic SSR and eight polymorphic EST-SSR loci were
      chosen after testing in 92 individuals. The number of alleles observed for these
      27 loci ranged from one to 17. The levels of observed and expected heterozygosity
      ranged from 0.000 to 1.000 and from 0.000 to 0.903, respectively. Most markers
      also amplified in C. obtusa var. formosana. Conclusions: The developed SSR and
      EST-SSR sequences are the first reported markers specific to C. formosensis.
      These markers will be useful for individual identification of C. formosensis and
      to distinguish cypress species such as C. obtusa var. formosana.

PMID- 30214839
TI  - Development and characterization of microsatellite loci for the endemic
      Thalictrum smithii (Ranunculaceae).
AB  - Premise of the Study: Microsatellite primers were developed for the gynodioecious
      Chinese endemic Thalictrum smithii (Ranunculaceae). Methods and Results: Thirty
      nine microsatellite primers were developed using the Fast Isolation by AFLP of
      Sequences COntaining repeats (FIASCO) method. Thirteen microsatellite loci were
      found to be highly polymorphic after screening 114 specimens (60 hermaphrodite
      and 54 female) from three T. smithii populations. The number of alleles per locus
      ranged from three to 13, and the levels of observed and expected heterozygosity
      per locus ranged from 0.000 to 1.000 and from 0.204 to 0.834, respectively.
      Twenty-six of these primers were polymorphic in T. petaloideum and T. finetii.
      Conclusions: These markers will be useful for examining genetic diversity,
      polyploidy, and mating system in populations of T. smithii and for guiding study
      on the evolution of speciation in Thalictrum.

PMID- 30214840
TI  - A refined method for digitally modeling small and complex plant structures in 3D:
      An example from the grasses (Poaceae).
AB  - Premise of the Study: A refined procedure is described for modeling small,
      intricate plant structures using computer-aided design software. The procedure
      facilitates the study of wind pollination in the family Poaceae and provides
      virtual biological illustrations for public outreach. Methods and Results:
      Spikelets were fixed in gFAA, dehydrated using ethanol and xylene, embedded in
      paraffin wax, and then sectioned with a rotary microtome. Images of serial
      sections were used as a reference for modeling the shape of bracts with splines
      in a computer-aided design program. Virtual models produced by this method have
      many potential uses; examples include geometric morphometric analyses and
      simulations of computational fluid dynamics. Conclusions: This protocol is a
      synthesis of modern biological illustration and engineering technology. Virtual
      models facilitate quantitative experiments that may address questions about
      reproductive biology, conditions shaping the form of anatomical support, or the
      morphological evolution of structures of biomechanical interest.

PMID- 30214842
TI  - A Case of Atypical Lipomatous Tumor that Dedifferentiated with Second Recurrence
      after Additional Resection.
AB  - Dedifferentiated liposarcoma is recognized as a type of liposarcoma that usually
      occurs concomitantly with the well-differentiated type. In this report, we
      discuss the case of a 65-year-old man who developed a dedifferentiated
      liposarcoma with second recurrence of an atypical lipomatous tumor. The patient
      first presented to us with an atypical lipomatous tumor of the right elbow for
      which he underwent a marginal resection. After five months, the patient
      experienced tumor recurrence for which he underwent another extended resection.
      Approximately 10 months following this surgery, the tumor recurred a second time
      for which he underwent another extended resection. Histopathological analysis of
      the second recurring tumor revealed a dedifferentiated liposarcoma. So far, two
      years following this resection, recurrence has not been observed. This is the
      first case of an atypical lipomatous tumor that dedifferentiated after the
      additional extended resection.

PMID- 30214841
TI  - Post-football Gonathrosis: Injuries and Surgeries are A Risk.
AB  - Football is one of the most popular sports in the world. Many studies have shown
      there is a high incidence of gonarthrosis in football players. The reason for
      this increase is said to be injuries to the meniscus, the anterior cruciate
      ligament (ACL) and the resulting surgeries. The incidence is significantly
      increased in players with knee injuries. The knee is also the most commonly
      injured site in football and the most common cause of surgery in football
      players. Together these injuries, particularly of the ACL or meniscus and the
      resulting surgeries, increase the risk of developing gonarthrosis in post
      football years.

PMID- 30214843
TI  - Atypical Presentation of Fibrodysplasia Ossificans Progressiva: A Case Report and
      Review of Literature.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease
      characterized by widespread areas of abnormal bone formation in muscles,
      ligaments, tendons and joint capsules. Typically, the symptoms begin in the first
      decade of life with episodes of painful inflammatory soft tissue swellings.
      Gradually, there occurs restriction of motion at various joints, severely
      limiting the activities of daily living and the quality of life of such patients
      by the third decade of life. There is no definite cure available for the disease
      and the current treatment options target symptomatic and palliative management.
      We describe the case of a 10-year-old child who presented to our institute with a
      severe disability of upper limbs due to joint contractures along with several
      bony masses at various locations of the body but without having any prior
      complaints of painful soft tissue lesions or the characteristic flare-ups of the
      disease ever. Identification of typical soft tissue ossified masses in the
      specific anatomic pattern, along with the presence of short and malformed great
      toes helped us in reaching the diagnosis. Surgical procedures including biopsies
      should be strictly avoided in such patients to prevent triggering the development
      of more lesions, which occurred in our patient after inadvertent removal of the
      first swelling by an orthopaedic specialist.

PMID- 30214844
TI  - Intrapelvic Localised Hydatid Cyst.
AB  - Hydatid cysts, caused by Echinococcus granulosus, is an important health problem
      in endemic areas. The disease can localize most commonly in the liver and lungs.
      Primary pelvic involvement is a rare condition. In this case report, we aimed to
      present a 75-year-old male patient with a pelvic mass, which was diagnosed
      preoperatively as a hydatid cyst.

PMID- 30214845
TI  - A Strange Case of Dissociative Identity Disorder: Are There Any Triggers?
AB  - We discuss a strange case of dissociative identity disorder, also known as
      multiple personality disorder. This article describes the case of a 55-year-old
      Caucasian woman with a history of substance use disorder with seven
      personalities. The patient describes a couple of triggers for her condition. More
      research is needed to understand these triggers.

PMID- 30214846
TI  - Local Failure Rate in Oropharyngeal Carcinoma Patients Treated with Intensity
      modulated Radiotherapy Without High-dose Clinical Target Volume.
AB  - PURPOSE: Our purpose was to evaluate whether omitting high-dose clinical target
      volume radiation (CTV-HD) around the gross tumor volume (GTV) in patients with
      oropharyngeal squamous cell carcinoma (OSCC) treated with intensity-modulated
      radiotherapy (IMRT) was associated with increased local failure. METHODS AND
      MATERIALS: Patients diagnosed with stage I to stage IV OSCC between December 2004
      and April 2017 were retrospectively reviewed. All patients were treated with
      radical radiotherapy using IMRT, with or without neoadjuvant or concurrent
      chemotherapy. In accordance with institution guidelines, CTV-HD was not used.
      Local failure was defined as disease persistence or reappearance at the primary
      tumor site. When primary failure was documented, the computed tomography/positron
      emission tomography (CT/PET) scan that showed primary failure was fused with the
      original treatment scan. Each recurrent tumor was contoured to evaluate the
      pattern of recurrence. Recurrences were categorized as in-field, marginal, or out
      of-field if >95%, 20%-95%, or <20% of the recurrent tumor volume, respectively,
      was encompassed by the 95% high-dose prescription isodose line of the original
      treatment plan. We then determined whether omitting CTV-HD was associated with
      increased locoregional failure. RESULTS: A total of 272 patients with OSCC were
      assessed. The median follow-up from initial treatment was 43 months (range: 3-194
      months). Seven patients were lost to follow-up. The overall five-year survival
      rate was 87%. The three- and five-year disease-free survival rates were 86% and
      83%, respectively. Forty-one patients had 53 treatment failures (16 were local,
      eight were regional, and 29 were distant; some patients had treatment failures in
      multiple locations). Fourteen (87.5%) of the local recurrences were in-field, one
      (6.25%) was marginal, and one (6.25%) was out-of-field. CONCLUSION: Our analysis
      of patients with oropharyngeal cancer suggests that local failure is mostly in
      field and potentially due to radioresistance, rather than a marginal miss of the
      tumor. It suggests that omitting CTV-HD is feasible and safe.

PMID- 30214847
TI  - Medium-term Electrophysiologic Effects of a Cellularized Scaffold Implanted in
      Rats After Myocardial Infarction.
AB  - Background Cardiac repair strategies are being evaluated for myocardial
      infarctions, but the safety issues regarding their arrhythmogenic potential
      remain unresolved. By utilizing the in-vivo rat model, we have examined the
      medium-term electrophysiologic effects of a biomaterial scaffold that has been
      cellularized with spheroids of human adipose tissue, derived from mesenchymal
      stem cells and umbilical vein endothelial cells. Methods Mesenchymal stem cells,
      which exhibit adequate differentiation capacity, were co-cultured with umbilical
      vein endothelial cells and were seeded on an alginate based scaffold. After in
      vitro characterization, the cellularized scaffold was implanted in (n=15) adult
      Wistar rats 15 min post ligation of the left coronary artery, with an equal
      number of animals serving as controls. Two weeks thereafter, monophasic action
      potentials were recorded and activation-mapping was performed with a multi
      electrode array. An arrhythmia score for inducible ventricular tachyarrhythmias
      was calculated after programmed electrical stimulation. Results The arrhythmia
      score was comparable between the treated animals and controls. No differences
      were detected in the local conduction at the infarct border and in the voltage
      rise in monophasic action potential recordings. Treatment did not affect the
      duration of local repolarization, but tended to enhance its dispersion.
      Conclusions The fabricated bi-culture cellularized scaffold displayed favorable
      properties after in-vitro characterization. Medium-term electrophysiologic
      assessment after implantation in the infarcted rat myocardium revealed low
      arrhythmogenic potential, but the long-term effects on repolarization dispersion
      will require further investigation.

PMID- 30214849
TI  - Brain Herniation Through the Cribriform Plate: Review and Comparison to
      Encephaloceles in the Same Region.
AB  - Herniations of the brain and/or meninges through an opening of the skull often
      occur through the foramen magnum, e.g., Chiari malformations and encephaloceles.
      The herniation of brain matter through the cribriform plate is a rare incident
      and has not been reported frequently. The presence of such an occurrence still
      requires attention and anatomical understanding. This review will examine the
      potential causes of cribriform plate herniation and its distinguishability to
      nasal encephaloceles. The sloping of brain tissue toward potential space/opening
      in response to elevated pressures in the cranium to accommodate for the added
      pressure are features seen in herniation. The presence of a pedicle and stalk
      seen in an encephalocele define its characteristics, which are not visible in a
      'classical' herniation. Cerebrospinal fluid (CSF) fistula commonly occurs at the
      cribriform plate, and due to the structural weakness, a pathway is formed. This
      is often seen in conjunction with meningoceles. Delineating between herniation
      and encephaloceles is important for both clinicians and neurosurgeons.

PMID- 30214848
TI  - The Role of Vitamin D in Brain Health: A Mini Literature Review.
AB  - Vitamin D is vital for our body as it regulates calcium homeostasis and maintains
      bone integrity. In this article, we will discuss how vitamin D aids in the
      function of neuronal and glial tissue and the many health consequences in a
      person with vitamin D deficiency. Some of the effects of vitamin D deficiency
      that will be discussed include the development of dementia caused by the increase
      of cerebral soluble and insoluble amyloid-beta (Abeta) peptides and a decrease of
      its anti-inflammatory/antioxidant properties, the link to depression by a
      reduction of the buffering of increased calcium in the brain, and vitamin D
      deficiency in expecting mothers linking to the development of autism and
      schizophrenic-like disorders, hypoxic brain injury, and other mental illnesses.
      Lastly, we will discuss how vitamin D deficiency is linked to the development of
      diabetes mellitus, its role in neuronal development and a decrease of microglial
      inflammatory function leading to increased brain infections.

PMID- 30214850
TI  - Distribution of Antisense Oligonucleotides in Rat Eyeballs Using MALDI Imaging
      Mass Spectrometry.
AB  - Oligonucleotide-based therapeutics such as antisense oligonucleotides, small
      interfering RNAs (siRNAs), decoy and aptamer have been extensively developed. To
      investigate the pharmacokinetics of oligonucleotide therapeutics, it is common to
      label a radioisotope in a nucleic acid and visualize it. However, if the labeled
      terminal nucleotide is decomposed by a nuclease in vivo, only the labeled
      nucleotide is detected, and it is impossible to observe the nucleic acid
      exhibiting the drug effect. The distribution of biomolecules, such as
      phospholipids, proteins, and glycolipids, can be obtained and visualized without
      labeling using matrix-assisted laser desorption/ionization imaging mass
      spectrometry (MALDI-IMS). MALDI-IMS is also used in pharmacokinetic analysis to
      visualize a parent drug and its metabolites simultaneously. In this study, we
      reported a methodology for oligonucleotides analysis by MALDI-IMS. When
      phosphorothioate antisense oligonucleotide was administered into the eyeball of
      rats, it reached the retina after 30 min without undergoing decomposition by
      nucleases.

PMID- 30214851
TI  - Mix-&-Read Determination of Mercury(II) at Trace Levels with Hybrid Mesoporous
      Silica Materials Incorporating Fluorescent Probes by a Simple Mix-&-Load
      Technique.
AB  - The synthesis, characterization, and application of mesoporous materials
      containing boron-dipyrromethene (BODIPY) moieties that allow the sensitive and
      selective detection of HgII in aqueous environments by fluorescence enhancement
      is reported. For this purpose, BODIPY dye I containing a thia-aza crown ether
      receptor as the fluorescent probe for the detection of HgII in aqueous
      environments is encapsulated into mesoporous materials to avoid self-quenching or
      aggregation in water. Determination of HgII is accomplished within a few seconds
      with high selectivity and sensitivity, reaching a limit of detection of 12 ppt.
      The determination of trace amounts of HgII in natural waters and in fish extracts
      is demonstrated by using our sensing material. The incorporation of the material
      into several MU-PAD strips yields a portable, cheap, quick, and easy-to-handle
      tool for trace HgII analysis in water.

PMID- 30214852
TI  - Structural Basis for the Inhibition of Cyclin G-Associated Kinase by Gefitinib.
AB  - Gefitinib is the molecular target drug for advanced non-small-cell lung cancer.
      The primary target of gefitinib is the positive mutation of epidermal growth
      factor receptor, but it also inhibits cyclin G-associated kinase (GAK). To reveal
      the molecular bases of GAK and gefitinib binding, structure analyses were
      conducted and determined two forms of the gefitinib-bound nanobody?GAK kinase
      domain complex structures. The first form, GAK_1, has one gefitinib at the ATP
      binding pocket, whereas the second form, GAK_2, binds one each in the ATP binding
      site and a novel binding site adjacent to the activation segment C-terminal
      helix, a unique element of the Numb-associated kinase family. In the novel
      binding site, gefitinib binds in the hydrophobic groove around the activation
      segment, disrupting the conserved hydrogen bonds for the catalytic activity.
      These structures suggest possibilities for the development of selective GAK
      inhibitors for viral infections, such as the hepatitis C virus.

PMID- 30214854
TI  - When better still might not be good enough.

PMID- 30214853
TI  - The associations of sedentary time and breaks in sedentary time with 24-hour
      glycaemic control in type 2 diabetes.
AB  - The aim of this study was to investigate the associations of accelerometer
      assessed sedentary time and breaks in sedentary time with 24-h events and
      duration of hypoglycaemia (<3.9 mmol/l), euglycaemia (3.9-7.8 mmol/l),
      hyperglycaemia (>7.8 mmol/l) and above target glucose (>9 mmol/l). Thirty-seven
      participants with type 2 diabetes (age, 62.8 +/- 10.5 years; body mass index,
      29.6 +/- 6.8 kg/m2) in Glasgow, United Kingdom were enrolled between February
      2016 and February 2017. Participants wore an activity monitor (activPAL3)
      recording the time and pattern of sedentary behaviour and a continuous glucose
      monitoring (CGM, Abbott FreeStyle Libre) for up to 14 days. Linear regression
      analyses were used to investigate the associations. Participants spent 3.7%,
      64.7%, 32.1% and 19.2% of recording h/day in hypoglycaemia, euglycaemia,
      hyperglycaemia and above target, respectively. There was a negative association
      between sedentary time and time in euglycaemia (beta = -0.44, 95% CI -0.86; 
      0.03, p = 0.04). There was a trend towards a positive association between
      sedentary time and time in hyperglycaemia (beta = 0.36, 95% CI -0.05; 0.78, p =
      0.08). Breaks in sedentary time was associated with higher time in euglycaemia
      (beta = 0.38, 95% CI 0.00; 0.75, p = 0.04). To conclude, in individuals with type
      2 diabetes, more time spent in unbroken and continuous sedentary behaviour was
      associated with poorer glucose control. Conversely, interrupting sedentary time
      with frequent breaks appears to improve glycaemic control. Therefore, this should
      be considered as a simple adjunct therapy to improve clinical outcomes in type 2
      diabetes.

PMID- 30214856
TI  - Comparative assessment of qualitative and quantitative perfusion with dual-energy
      CT and planar and SPECT-CT V/Q scanning in patients with chronic thromboembolic
      pulmonary hypertension.
AB  - Background: The purpose of this study was to compare the qualitative and
      quantitative assessment of perfusion on dual-energy CT (DECT) and planar and
      single photon emission computed tomography (SPECT)-CT V/Q scanning in patients
      with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Nineteen
      patients with known CTEPH underwent both DECT and SPECT-CT V/Q scanning. Sixteen
      of these patients underwent planar V/Q imaging concurrently. Two readers
      independently graded DECT-perfused blood volume (PBV) defects on a four-point
      scale (0= normal, 1= mild <25%, 2= moderate 25-50%, 3= severe >50%). A grade was
      given for each lung lobe and for each of 18 lung segments. One reader graded the
      SPECT-CT images similarly. Quantitative measurements of lung perfusion were
      calculated with DECT and planar V/Q scanning for 16 of these patients. Results:
      The inter-reader agreement on DECT was strong with agreement in 85% (258/304) of
      segments (kappa =0.86) and 84% (80/95) of lobes (kappa =0.82). The inter-modality
      agreement between DECT and SPECT-CT was lower. Readers 1 and 3 agreed in only 34%
      (103/304) of segments (kappa =0.25) and 33% (31/94) of lobes (kappa =0.22).
      Agreement between readers 2 and 3 was similar. Correlation between quantitative
      measurements with DECT and planar V/Q imaging was poor and ranged from 0.01 to
      0.45. Conclusions: Inter-observer agreement in subjective grading of PBV maps is
      excellent. However, inter-modality agreement between DECT and SPECT-CT is modest.
      Automated quantification values of PBV maps correlate poorly with established
      tools like planar V/Q imaging. These differences need to be kept in mind during
      clinical decision making.

PMID- 30214855
TI  - Extent of coronary atherosclerosis and arterial remodelling in women: the NHLBI
      sponsored Women's Ischemia Syndrome Evaluation.
AB  - Background: Information regarding the pathogenesis of ischemic heart disease
      (IHD) in women is limited. Sex-specific responses to atherosclerosis and coronary
      arterial remodelling in women versus men have been hypothesized, but limited
      study exists. Methods: Case-matched study of 174 women with suspected ischemia
      referred for coronary angiography: 87 with non-obstructive coronary artery
      disease (CAD) (no luminal diameter stenosis >20% in any coronary artery) and 87
      age and ethnicity matched women with obstructive CAD. Groups were compared with
      regard to atheroma burden and coronary arterial remodelling assessed by coronary
      artery intravascular ultrasound (IVUS). Results: IVUS revealed more extensive
      atheroma with obstructive CAD vs. those without obstructive CAD, with greater
      percent atheroma volume (PAV) (36.1%+/-9.8% vs. 25.4%+/-9.1%, P<0.0001), total
      atheroma volume (TAV) (140.8+/-58.7 vs. 98.8+/-46.9 mm3, P<0.0001) and percentage
      of images containing plaque (70.0%+/-30.5% vs. 35.7%+/-32.6%, P<0.0001).
      Adjusting for risk factors, PAV (35%+/-1% vs. 28%+/-1%, P=0.0008), TAV (131+/-7
      vs. 115+/-7 mm3, P=0.110) and percentage of images containing plaque (66%+/-4%
      vs. 45%+/-5%, P=0.0008) remained greater with obstructive CAD. Obstructive CAD
      was associated with smaller lumen volumes (251.9+/-92.8 vs. 289.7+/-91.8 mm3,
      P=0.005), but surprisingly, the external elastic membrane (EEM) volume was very
      similar comparing the groups (392.7+/-128.1 vs. 388.6+/-113.7 mm3, P=0.910).
      Conclusions: Our findings suggest that women referred to angiography for
      suspected ischemia, have differing patterns of coronary arterial response to
      injury with regard to accumulation of atherosclerosis and compensatory
      remodelling related to the presence and absence of obstructive CAD. Preservation
      and cultivation of compensatory arterial remodelling may be a novel CAD
      therapeutic target.

PMID- 30214857
TI  - Non-cardiac comorbidities in adults with inherited and congenital heart disease:
      report from a single center experience of more than 800 consecutive patients.
AB  - Background: As a result of improved surgical and therapeutical management, more
      than 90% of patients with congenital heart disease (CHD) reach adulthood.
      However, the natural course of CHD is complicated by noncardiac medical problems.
      Aim of the study was to evaluate noncardiac comorbidities in a contemporary
      cohort of adults with CHD (ACHD). Methods: In a tertiary care center for ACHD,
      821 consecutive patients, admitted to the outpatient clinic, were evaluated for
      clinically relevant noncardiac comorbidities. Results: The consecutively included
      patients (age: range, 15-80 years; 56% female) represent all types and severity
      grades of acyanotic and cyanotic CHD. A considerable proportion of ACHD had
      significant noncardiac comorbidities, which have the potential to profoundly
      influence the natural course of the underlying disease. In 95.5%, relevant non
      cardiac comorbidities were apparent, that could be related to 16 special medical
      fields as endocrinologic/metabolic disease, gastroenterology/hepatology,
      gynecology/obstetrics, angiology, orthopedics, neurology/psychiatry and others.
      Most frequently seen comorbidities were endocrine and metabolic disorders
      (43.97%). Conclusions: Non-cardiac comorbidities are increasingly common in ACHD.
      The data revealed non-cardiac comorbidities as they were presented in the cohort
      of ACHD seen in a tertiary center. The study proves that ACHD with significant
      non-cardiac comorbidities need multidisciplinary care by medical organ
      specialists, aside the congenital cardiologist, with a deep knowledge about
      congenital heart defects, the special effects of the organ disease on the
      particular heart defect and, how the heart defect may affect the course of the
      particular organ disease. The study may create the basis for the development of
      screening programs for comorbidities in ACHD as well as a multidisciplinary
      concept for diagnosis and treatment of concomitant disorders or for disease
      prevention. Particularly disease prevention may improve quality of life as well
      as the further fate of the affected patients.

PMID- 30214858
TI  - Hypertension in Sudanese individuals and associated risk factors: the critical
      intersection between salt and sugar intake.
AB  - Background: Hypertension is common problem across the globe. The aim of this
      study was to assess the prevalence of hypertension and impact of salt and sugar
      intake in Sudanese population. Methods: A descriptive cross sectional study,
      included 323 of participants in Khartoum state. The data collection was performed
      to gather demographic information, physical activity and dietary habits. In
      addition to measurement of blood pressure (BP), weight and height measurement for
      calculation of body mass index (BMI). Results: Among the 323 respondents (males
      were 171), 29 (9%) are known hypertensive, 60 (18.6%) are diagnosed to be
      hypertensive. Therefore, the prevalence of hypertension is 27.6%. Hypertension
      was significantly associated with male sex, increasing age, obesity, low physical
      activity, salt and sugar intake. Logistic regression analysis showed that
      increasing age, obesity and high sugar intake are absolute predictors for
      hypertension in Sudanese population. Conclusions: The prevalence of hypertension
      was 27.6%. Hypertension in Sudanese individuals was associated with high sugar
      and salt intake, obesity and increase in age. Therefore, decreasing sugar and
      salt intake should be advocated by health authorities and the public in Sudan.

PMID- 30214859
TI  - Role of preoperative cardiac CT in the evaluation of infective endocarditis:
      comparison with transesophageal echocardiography and surgical findings.
AB  - Background: Significant improvement of computed tomography (CT) technology in the
      last decade has led to more use of this modality for evaluating infective
      endocarditis (IE) especially since the introduction of high resolution
      electrocardiogram (ECG) synchronized multiphasic (4D) acquisition. While there
      are a number of reports on the accuracy and value of 4D CT for evaluation of IE,
      there is no published data regarding the performance of single-phase ECG gated CT
      for assessment of IE. The purpose of this study is to evaluate the sensitivity
      and specificity of preoperative single-phase ECG-gated CT imaging versus
      transesophageal echocardiography (TEE) in the assessment of complications related
      to IE, with comparison to surgical findings. Methods: Among 899 patients with
      surgically proven IE in our database, 122 underwent contrast-enhanced ECG cardiac
      CT and were included in the study; 84 of these patients also underwent TEE.
      Results: Overall, there was no significant difference between CT and TEE in the
      identification of pseudoaneurysm/abscess and dehiscence. For the detection of
      pseudoaneurysm/abscess in prosthetic valves, CT demonstrated higher sensitivity
      (81% vs. 64%) and specificity (75% vs. 33%) in patients with mechanical aortic
      valves; TEE demonstrated marginally higher sensitivity (72% vs. 63%) and
      specificity (80% vs. 73%) in patients with bioprosthetic aortic valves, although
      the differences are not statistically significant. TEE demonstrated significantly
      higher sensitivity (85% vs. 16%) in identifying vegetation in all patients
      (P<0.0001), including patients with prosthetic valves (sensitivity, 78% vs. 19%).
      The combined imaging findings of CT and TEE demonstrated improved sensitivity in
      identifying pseudoaneurysm/abscess and slightly improved detection of prosthesis
      dehiscence. Conclusions: Preoperative single-phase gated CT can be seen as
      complementary to TEE in assessing complications of suspected IE or may be
      substituted for TEE when vegetation or dehiscence is depicted on transthoracic
      echocardiography and the patient has a contraindication to TEE.

PMID- 30214860
TI  - Arterial stiffness in black African ancestry patients with chronic kidney disease
      living in Cameroon.
AB  - Background: Increased aortic pulse wave velocity (PWV), a direct measure of
      arterial stiffness (AS) is an independent predictor of cardiovascular events
      (CVEs) in chronic kidney disease (CKD) patients. This study assessed the patterns
      of PWV among Cameroonian patients with CKD in whom that marker of early vascular
      aging has not been explored so far. Methods: We enrolled 150 Black African
      patients (mean age: 52+/-15 years, 56.7% males) with CKD in a cross-sectional
      study conducted at Douala General Hospital, Douala, Cameroon. Sociodemographic,
      anthropometric and biologic variables, blood pressure (BP) and PWV were recorded
      in all participants. Estimated aortic PWV was measured using a Mobil-O-Graph
      automatic brachial oscillometric device. Results: PWV increased with aging
      (P<0.0001), and PWV adjusted for age, sex, body mass index and mean arterial BP
      (MAP) was higher in non-dialysed (n=90) than in hemodialysed (n=60) patients,
      even in pre-dialysis: 8.5+/-2.0 vs. 7.9+/-1.4 m/s (P=0.026); and in post
      dialysis: 8.5+/-2.0 vs. 7.8+/-1.5 m/s (P=0.008). The mean PWV of all study
      participants was 8.2+/-1.8 m/s, with 61.3% of patients having a PWV >=8.2 m/s,
      indicative of subclinical damage to the aorta, which was more pronounced in non
      dialysis (67.8%) than in hemodialysis (53.3%) patients (P=0.033). Multivariable
      analysis performed in all participants revealed that advanced age, MAP and
      tobacco use were independently associated with PWV (all P<0.05). Conclusions: Our
      findings suggest increased AS in Cameroonian CKD non-dialyzed as compared to
      dialyzed patients. Slower PWV in patients on maintenance hemodialysis suggests
      improvement of aortic distensibility following dialysis. However, further large
      scale studies are needed to confirm our findings and to improve understanding of
      the underlying mechanisms of arterial stiffening in black African ancestry
      patients with CKD.

PMID- 30214861
TI  - Exercise capacity in asymptomatic patients with significant primary mitral
      regurgitation: independent effect of global longitudinal left ventricular strain.
AB  - Background: Despite preserved left ventricular ejection fraction (LVEF), patients
      with significant primary mitral regurgitation (MR) often have reduced exercise
      capacity. In asymptomatic patients with >=3+ primary MR undergoing rest-stress
      echocardiography (RSE), we sought to evaluate the incremental impact of left
      ventricular global longitudinal strain (LV-GLS) on exercise capacity. Methods: A
      total of 660 asymptomatic patients with >=3+ primary MR, non-dilated LV and LVEF
      >=60% (mean age, 57+/-14 years, 66% men, body mass index or BMI 25+/-4 kg/m2) who
      underwent RSE at our center between 2001 and 2013 were included. Standard RSE
      data were obtained. Average resting LV-GLS was measured using Velocity Vector
      Imaging. Results: Mean mitral effective regurgitant orifice, resting right
      ventricular systolic pressure (RVSP) and LV-GLS were 0.45+/-0.2 cm2, 31+/-12 mmHg
      and -21.7%+/-2%, respectively; 28% had flail mitral leaflet. Mean metabolic
      equivalents (METs) and post-stress RVSP were 9.9+/-3, and 46+/-15 mmHg; 28%
      achieved <100% age-gender predicted METs. No patient had ischemia or significant
      arrhythmias. On logistic regression, resting LV-GLS [odds ratio (OR), 1.40, 95%
      confidence interval (CI): 1.21-1.55, BMI (OR, 1.11, 95% CI: 1.06-1.17)] and
      resting RVSP 1.22 (1.02-1.49) were independent predictors of exercise capacity.
      Area under the curve for association between 100% age-gender predicted METs and
      various factors were as follows: (I) BMI (0.60, 95% CI: 0.55-0.65, P<0.001); (II)
      resting RVSP (0.57, 95% CI: 0.52-0.62, P=0.006) and LV-GLS (0.66, 95% CI: 0.61
      0.70, P<0.001). Conclusions: In asymptomatic patients with >=3+ primary MR, non
      dilated LV and preserved LVEF, LV-GLS is independently associated with exercise
      capacity, beyond known predictors.

PMID- 30214862
TI  - Liver enzyme trends in patients taking uninterrupted metformin before and after
      coronary surgery.
AB  - Background: Metformin is an oral antidiabetic agent belonging to the biguanide
      class of antidiabetics. Possible novel applications for metformin in
      cardiovascular disease might exist. The aim of this study was to verify a
      possible association between pre-operative metformin administration and
      protection against ischemia-induced liver injury in diabetic patients undergoing
      coronary artery bypass grafting (CABG) surgery. Methods: A retrospective case
      control series was conducted at a single center. Two hundred consecutive diabetic
      patients underwent isolated on-pump CABG during a 12-month span (July 2015 - July
      2016). Metformin was uninterrupted in patients who took this drug prior to CABG;
      68 patients were metformin users (34%) while 132 patients were taking other
      antidiabetic agents (66%). Liver enzymes and other organ markers were
      consecutively recorded daily for 7 days after surgery and expressed as medians
      with interquartile range (IQR). Results: Both the metformin and non-metformin
      group of patients had similar pre-operative demographic characteristics. The
      median (IQR) post-operative cardiac enzyme creatinine kinase (CK) MB fraction was
      significantly lower in the metformin group [46.4 U/L (35.8-66.5) vs. 66.5 U/L (44
      94.5), P=0.005]. Total bilirubin [0.58 (0.48-0.82) mg/dL vs. 0.67 (0.56-0.95)
      mg/dL, P=0.021], the transaminase aspartate aminotransferase (AST) [32.5 U/L
      (25.0-42.0) vs. 37.5 U/L (28.5-56), P=0.011], the transaminases alanine
      aminotransferase (ALT) [48.5 U/L (40.0-64.0) vs. 57.0 U/L (44.0-77.0), P=0.040]
      and lactate dehydrogenase (LDH) [320.0 U/L (273.5-367.2) vs. 356.5 U/L (289.5
      427), P=0.014] were significantly lower in the metformin group. No differences
      were noted in clinical outcomes. Conclusions: In this limited retrospective
      study, the diabetic patients who took metformin before and after undergoing CABG
      appeared to have a reduced post-operative surge in the total bilirubin and
      transaminase liver enzymes. Metformin's role in mitigating oxidative stress in
      liver cells might explain this observation. Further experimental studies are
      warranted to verify this possible effect.

PMID- 30214864
TI  - Increasing myocardial infarction mortality trends in a middle-income country.
AB  - Background: Developed countries continue to show a decrease in cardiovascular
      disease (CVD) mortality. Little is known about CVD mortality trends in low and
      middle-income countries. The aim of our study is to describe myocardial
      infarction (MI) mortality trends and evaluate if differences between ethnic
      groups and geographic regions are present among the Ecuadorians with acute MI.
      Methods: We conducted a cross sectional analysis mortality national registry and
      included deaths related to MI between 2012 and 2016 that had complete demographic
      data. To describe the general population, we used the 2010 census and applied
      estimates as population projections. We calculated age and sex standardized MI
      mortality rates per 100,000. We compared trends in MI mortality rate for every
      ethnic group and geographic region and used linear regression to estimate
      predictors of the changing mortality rates. Results: We included 18,277 MI deaths
      between the years 2012 and 2016. The mean age of death was 73.6+/-19.5, 59% were
      male and 33% were illiterate. From 2012 to 2016, the standardized MI mortality
      rate increased from 51 to 157 deaths per 100,000. The most significant predictors
      of the increasing mortality rate were living in the coast (beta=0.10), belonging
      to a mixed race (beta=-0.033) and the year of death (beta=0.013). Conclusions:
      Our study found a worrisome increase in MI mortality between 2012-2016 in
      Ecuador, a middle-income country in South America. This rapid increase seems to
      be driven by geographic and racial differences. A thorough evaluation of the
      causes of this increase has to be undertaken by the Ecuadorian health
      authorities.

PMID- 30214865
TI  - Handheld echocardiography for screening and control of rheumatic heart disease
      study in Gezira state, Sudan: a double approach model.
AB  - Background: Rheumatic heart disease (RHD) is prevalent in Sudan's rural areas
      including Gezira state in central Sudan. We initiated a control program aiming at
      measurement of the echocardiographic (echo) prevalence of RHD, training of health
      workers and public awareness. Methods: This is a cross-sectional and
      interventional study conducted in Gezira State, Al Managil Locality from Nov 2016
      to February 2018. We used handheld echo (HHE) to detect the prevalence of RHD in
      school children and those tested positives were referred for standard echo. In
      addition, training on detection of RHD for health professionals was offered using
      training modules for physicians and nurses. Evaluation of health facilities was
      carried out using a questionaire. This was coupled with educational sessions to
      increase public awareness about RHD using posters and pamphlets. Results: Two
      thousand and one hundred twenty-nine school children were screened, 36 cases were
      positive by HHE, out of these 31 underwent standard echo and 5 were confirmed to
      have RHD, giving an echo prevalence of 2.3/1,000. All cases had mild mitral
      regurgitation. Knowledge, attitudes and practices of 175 health workers were
      assessed then a tailored training program was implemented. Practices that are not
      compatible with Sudan's RHD Guidelines were detected including performing skin
      testing prior to administration of benzathine penicillin and under-utilization of
      local anesthetic to decrease the pain when giving the injection. Benzathine
      penicillin was available in only 32% of health facilities and only 25% of their
      personnel received training in RHD management. Conclusions: RHD echo prevalence
      in Gezira is relatively high and the health system needs to be strengthened. A
      double approach, screen-to-control program that utilizes HHE screening, health
      workers' training, public awareness and providing medical supplies in primary
      health care centers is feasible.

PMID- 30214863
TI  - Air pollution and telomere length: a systematic review of 12,058 subjects.
AB  - Background: Over recent decades, adverse effects of ambient air pollution on the
      cardiovascular system have been clearly demonstrated. However, the underlying
      mechanisms are not fully elucidated. Air pollution may accelerates biological
      aging and thereby the susceptibility to cardiovascular diseases (CVDs). Telomeres
      are tandem repetitive DNA complexes that play a critical role in maintaining
      chromosome stability. There are, however, heterogeneities among the reported
      effects of air pollution on telomere. This study sought to evaluate the existing
      literature on the association between air pollution and telomere length (TL).
      Methods: Two reviewers independently searched on electronic databases including
      PUBMED, EMBASE, SCOPUS, WEB OF SCIENCE and Ovid. The key terms were "air
      pollution" and "telomere" without language restriction. Articles relating to
      tobacco smoke were excluded. Results: A total of 12,058 subjects from 25 articles
      remained for final review. All were observational studies: 14 cross-sectional, 6
      cohort and 5 case-control studies. Nineteen (76%) assessed leukocyte telomere
      length (LTL) of which 15 found associations between air pollution and shorter TL,
      2 with longer TL, 1 had mixed results, and a study of patients with type 2
      diabetes found non-significant associations with TL. One found longer TL from
      saliva. The remaining studies were of placental cells, buccal cells or sperm and
      all reported shorter TL associated with air pollution. Particulate matter (PM)
      was investigated in 8 articles, and the remainder assessed black carbon (BC),
      benzene, lead, cadmium and polycyclic aromatic hydrocarbon (PAH). Geographically,
      11 studies were conducted in Europe, with 10 in Asia and 4 in North America.
      While all followed Cawthon's protocol for TL assessment, discordance in the
      reporting formats did not allow us to perform a quantitative meta-analysis.
      Conclusions: Most of the studies support the association of shorter TL with air
      pollution. Uniform reporting format would be warranted for future studies to
      estimate true effect size of air pollution on TL.

PMID- 30214866
TI  - A case of mislabeled textbooks: misnomer of the traditional "bicaval" view.
AB  - Since the early beginning of the transesophageal echocardiography (TEE) era,
      standardized tomographic views describing cardiac key structures have been
      provided. They have become the basis of TEE and have not been modified for
      decades. During our recent structural interventional cases, it has come to our
      attention that the structure frequently labeled "inferior vena cava" in textbooks
      and journal articles illustrating the bicaval TEE view is, in fact, the coronary
      sinus. Our manuscript illustrates our observation.

PMID- 30214867
TI  - Very early antepartum pregnancy-associated spontaneous coronary artery dissection
      case report.
AB  - Spontaneous coronary artery dissection (SCAD) is an elusive cardiovascular
      disease that is increasingly recognized. Classically, pregnancy had been
      perceived as a notable risk factor for SCAD. However, modern studies had revealed
      that pregnancy-associated SCAD (PASCAD) accounted for fewer cases than previously
      thought. The majority of PASCAD cases occur in women post-partum. We describe a
      case of a 30-year-old woman who presented with SCAD while 10 days pregnant, which
      is the earliest PASCAD case reported in the literature.

PMID- 30214868
TI  - Intraarticular extravasation, an unusual complication of computed tomographic
      angiography performed with intraosseous needle intravenous access.
AB  - Off label use of intraosseous needles (IONs) for contrast media (CM) injection
      during computed tomographic angiography (CTA) has been reported in small case
      series and isolated case reports. Presently, complications specific to this novel
      indication are essentially unknown. In this communication, we report an
      extravasation of CM from the intramedullary space of the humerus into the
      glenohumeral joint space during an ION injection of CM during a CTA of the head,
      neck, and chest. Although clinically insignificant in this case, a more severe
      intraarticular extravasation could have had both short or long term adverse
      sequelae. Practitioners of CTA should be aware of this potential complication.

PMID- 30214869
TI  - Pericarditis-complicated takotsubo cardiomyopathy in a patient with rheumatoid
      arthritis.
AB  - A 64-year-old woman with medication-controlled rheumatoid arthritis (RA) was
      admitted to our hospital complaining of chest pains. An electrocardiogram showed
      elevated ST-segments in the inferior leads, and inverted T-waves in the left
      precordial leads. Left ventriculography demonstrated apical ballooning, and
      cardiac magnetic resonance imaging demonstrated apical ballooning of the left
      ventricle, and moderate pericardial effusion. The patient was diagnosed with
      takotsubo cardiomyopathy (TTC), complicated by pericarditis. In the literature,
      autoimmune disorders have been associated with TTC. We suggest that this
      patient's pericardial effusion was caused by TTC, and that her coexisting RA
      might have played a role in the etiology of the significant pericardial fluid
      accumulation.

PMID- 30214870
TI  - Transcatheter aortic valve replacement with intracardiac echocardiography from
      the right internal jugular vein.
AB  - Transesophageal echocardiography (TEE) is a useful imaging modality to guide
      transcatheter aortic valve replacement (TAVR). The limitations of TEE include the
      need for general anesthesia (GA) and endotracheal intubation. In Europe, TAVR
      under local anesthesia (LA) is usually performed without TEE. An intracardiac
      echocardiography (ICE) catheter may be used as an alternative to TEE, but the
      catheter is usually inserted from the femoral vein (FV-ICE). There are some
      reports of TAVR with FV-ICE; however, there are no reports of ICE inserted from
      the right internal jugular vein (JV-ICE). In the first case of its kind, we
      successfully performed TAVR under LA with JV-ICE. JV-ICE allows for the
      evaluation of perioperative hemodynamics, measurement of the aortic valve
      complex, and assessment of major complications during the procedure without
      interference from the operator or fluoroscopes; these represent a distinct
      advantage over TEE, transthoracic echocardiography, and FV-ICE. Moreover, there
      is no need for the echocardiologist to use maximal barrier precautions; the
      catheter can be operated in the standing position, like TEE; and operability is
      higher than that with FV-ICE. TAVR with JV-ICE is a promising alternative to TAVR
      under GA with TEE and TAVR under LA with FV-ICE.

PMID- 30214871
TI  - Leadless left ventricular endocardial pacing: a real alternative or a luxury for
      a few?

PMID- 30214872
TI  - Cardiac resynchronization therapy with wireless left ventricular endocardial
      pacing: is this the direction to go?

PMID- 30214873
TI  - Mechanically expanding transcatheter aortic valves: pros and cons of a unique
      device technology.

PMID- 30214874
TI  - Sacubitril/valsartan: a cardiovascular drug with pluripotential actions.

PMID- 30214875
TI  - Metabolic effects of sacubitril/valsartan: are they relevant in clinical
      practice?

PMID- 30214876
TI  - Head to head transcatheter heart valve comparisons: when theory becomes reality.

PMID- 30214877
TI  - Fractional flow reserve at the crossroad between revascularization and medical
      therapy.

PMID- 30214878
TI  - Stephen Y. Chan: perseverance through criticism is essential for success in
      cardiovascular research.

PMID- 30214879
TI  - Lines of thought.

PMID- 30214880
TI  - Improvement in Confidence Levels for the Management of Paediatric Cardiac Arrests
      in Medical Students Following a Training Course.
AB  - Background: Newly qualified doctors lack competency in handling a cardiopulmonary
      resuscitation. The ability to recall CPR fundamentals have been shown to be
      inadequate. Of greater concern is that medical students over - estimate their
      ability to deliver such aid in a real - world setting. As most medical students
      are only taught adult BLS they are often unskilled and/or unhelpful in managing
      paediatric specific emergencies. This fact is supported by the poor outcomes
      demonstrated in delivering successful Paediatric Basic Life Support (PBLS).
      Objectives: Our aim was to evaluate the baseline confidence levels of medical
      students in dealing with a paediatric cardiac arrest (PCA) and the improvement
      seen following a PBLS training course. Methods: A prospective study was conducted
      on 51 medical students who attended an established one - day PBLS and first aid
      course at one UK medical school. Participants were requested to complete a
      questionnaire directly prior to and after the course. Results: Following the
      delivery of the training, the cohort reported a statistically significant (P <
      0.05) increase in mean confidence with PCA from 2.2/10 (2.2 out of 10) to 7.5/10.
      A pre - training mean confidence score of 2.6/10 was observed for Year 4 and 5
      students who are close to graduating. Conclusions: Our findings clearly
      demonstrate very poor confidence among medical students with PCA at all stages of
      their training. We would strongly advocate the inclusion of a PBLS component in
      medical school curriculums so that future doctors are adequately prepared to
      deliver PBLS with confidence.

PMID- 30214882
TI  - Generalized Tonic Colonic Seizure Followed by Loss of Consciousness Early After
      Using Low Dose of Tramadol: A Case Report.
AB  - Introduction: Despite high efficacy and safety of tramadol as a pain relieving
      analgesic, some minor side effects have been reported following its consumption.
      However, very rarely, serious and life-threatening side effects may appear
      following administration of tramadol. Case Presentation: This research describes
      a case of tramadol poisoning that appeared with acute seizure needing emergent
      and intensive cares. In the described case, using a low dose of tramadol (200 mg,
      orally), the patient experienced generalized tonic colonic seizure followed by
      loss of consciousness and shoulder dislocation due to trauma, requiring admission
      to the intensive care unit. Conclusions: As shown in the study, even using a low
      dose of tramadol might lead to acute generalized seizure with loss of
      consciousness and the need for intensive care.

PMID- 30214881
TI  - The Effectiveness of 2% Lidocaine Gel Compared to 0.5% Tetracaine Eye Drop As
      Topical Anesthetic Agent for Phacoemulsification Surgery.
AB  - Background: Topical anesthetics have become the primary choice in
      phacoemulsification procedures for cataract extraction. The most common topical
      anesthetic drug used is 0.5% tetracaine eye drops. Repeated administration of
      0.5% tetracaine drops can cause corneal epithelial damage. Two percent lidocaine
      gel is latest option which has longer contact time with corneal epithelium.
      Objectives: To compare the effectiveness of 2% lidocaine gel with 0.5% tetracaine
      drops in phacoemulsification surgery. Methods: The study was a single blinded
      randomized clinical trial from March to July 2017 in patients underwent
      phacoemulsification cataract surgery. There were 72 subjects with age >= 40 years
      old who received randomization and divided into 2 groups: 2% lidocaine gel group
      and 0.5% tetracaine eye drop group. Topical anesthetics were applied 5 minutes
      before surgery. Five minutes after surgery, pain scale perceived during surgery
      was assessed by using a numerical rating scale. At the end of surgery, the
      subject filled the satisfaction questionnaire on topical anesthetic drugs
      administered. The ophthalmologists were also given a satisfactory questionnaire
      for topical anesthetic drugs selected for the procedure. Results: The median pain
      scale for 2% lidocaine gel group pain scale was 1; meanwhile, the median pain
      scale for 0.5% tetracaine eye drops was 3 (P < 0.05). Conclusions: Two percent
      lidocaine gel was more effective in relieving pain during phacoemulsification
      cataract surgery compared with 0.5% tetracaine drops.

PMID- 30214884
TI  - Comparison of Effects of Melatonin and Gabapentin on Post Operative Anxiety and
      Pain in Lumbar Spine Surgery: A Randomized Clinical Trial.
AB  - Background: Surgery is one of the stressors that cause physiological and
      psychological stress. Anxiety and pain and their complications are very important
      in anesthesiology and many researches have been done to decrease or eliminate
      them. This training was done to compare the effect of melatonin and gabapentin on
      pain and anxiety during lumbar surgery. Methods: This study was a double-blinded
      clinical trial conducted on 90 patients undergoing lumbar surgery with general
      anesthesia in Golestan Academic Hospital in 2017. Patients were randomly assigned
      into 3 groups: 30 patients received 6 mg melatonin, 30 patients received 600 mg
      gabapentin, and 30 patients were on placebo (control), 100 minutes
      preoperatively. All patients were given a fixed method of anesthesia. The pain
      intensity and patients' satisfaction from analgesia measured at 1, 2, 6, 12, and
      24 h after surgery. The anxiety was measured 15 minutes before surgery and 1, 2,
      6, 12, and 24 h after surgery. Results: In our study, there was a significant
      difference between mean Visual Analog Score between melatonin and gabapentin
      groups in comparison to placebo (P = 0.02). The intensity of anxiety among the
      groups was lower in melatonin and gabapentin groups in comparison to placebo (P =
      0.01). Conclusions: The results show that pretreatment with melatonin or
      gabapentin decreases anxiety and pain in lumbar surgery.

PMID- 30214883
TI  - Investigation of the Effect of Hypnotic Anesthesia on Nerve Conduction Velocity
      (NCV).
AB  - Background: Hypnosis is a psychological method used for treatment of different
      types of disorders and illnesses. This technique is also used in surgical
      interventions. Many studies proved the efficacy of hypnosis in medical treatment.
      However, the mechanism of hypnosis is unclear for scientists. To find out if the
      peripheral nervous system has a role in hypnotic anesthesia, we aimed to
      investigate the effect of hypnotic anesthesia on nerve conduction velocity (NCV).
      Methods: In this study, healthy volunteers with high hypnotizability entered the
      study. First, The NCV test was performed in both hands of participants and then
      they all underwent hypnosis. Hypnotic anesthesia was induced in the right hand of
      all subjects followed by painful stimuli in their hand by vascular clasping.
      Then, the NCV test was repeated in both hands again. Data were analyzed by SPSS
      version16. Results: The group study consisted of 13 (65%) women and 7 (35%) men
      with their age ranging between 14 to 52 years. According to the results, the mean
      values of sensory latency, and NCV changed from 3.225 ms and 54.355 m/s before
      hypnotic anesthesia to 3.32 ms and 55.3 m/s after hypnotic anesthesia in right
      hand, respectively. Results showed that there was a significant difference
      between data before and after hypnotic induction (P < 0.001). The covariance test
      also indicated a significant difference between the data obtained from both hands
      (P < 0.001). Conclusions: In contrast to our hypothesis, the NCV test showed an
      increase after the hypnotic anesthesia. However, increase in NCV did not lead to
      experience pain after the painful stimuli. It seems that central nervous system
      should be involved in this process.

PMID- 30214885
TI  - Normal Reference Interval of WBC Count After On - Pump Coronary Artery Bypass
      Graft; When Values Could Be Misleading.
AB  - Background: Applying the cardiopulmonary pump produces inflammatory responses and
      induces leukocytosis. White Blood Cell (WBC) count has a diagnostic value for
      detecting different infections. In this study, we want to redefine the normal
      value reference intervals of WBC count in Coronary Artery Bypass Graft (CABG)
      patients, to prevent misdiagnose leukocytosis as a sign of infection. Methods: In
      an observational study, 140 patients who underwent on - pump CABG were enrolled
      to find out normal values of the reference interval. WBC counts were evaluated
      for all of them one day before the operation, first 30 minutes of ICU entrance,
      after 24 hours, and 48 hours after operation. Normal values of reference
      intervals were calculated for each measurement by two different statistical
      methods. Results: There were 102 men and 38 women with age average of 61 years.
      There was no significant difference between genders' WBC counts before operation
      (P = 0.151), ICU entrance (P = 0.391), 24 hours after surgery (P = 0.698), and 48
      hours after surgery (P = 0.523). The mean values of WBC after surgery were higher
      than the normal range of reference interval and had an increasing trend in the
      first 48 hours after surgery. The WBC values were significantly different between
      pre and post operation (before operation and ICU admission (P = 0.001), ICU
      admission and 24 hours later (P = 0.001), 24 hours after surgery, and 48 hours
      after surgery (P = 0.001)). All post - operative reference values were
      significantly higher than the range for the general population. Conclusions:
      There is a significant increase in WBC count after on - pump CABG. The normal
      range of WBC should be revised and adjusted to prevent misinterpretation as a
      sign of infection.

PMID- 30214886
TI  - Effect of Local Fibrinogen Administration on Postoperative Bleeding in Open
      Prostatectomy Surgery.
AB  - Background: Open prostatectomy is still accompanied by some postoperative
      bleeding. Prescribing fibrinogen to promote clot formation in patients with
      bleeding is of critical importance. This research studied the effects of local
      injection of fibrinogen on level of postoperative bleeding in open prostatectomy.
      Methods: Overall, 44 patients were randomly entered in a study on open
      prostatectomy. Patients in the intervention group received local injections of
      500 mg fibrinogen (20 mL) dissolved in distilled water, and the control group
      patients only received 20 mL of normal saline, where the injections were given by
      the surgeon at the prostatectomy operation site. All patients were tested for
      hemoglobin, hematocrit, PT, PTT, INR, and fibrinogen level. Also, the amount of
      blood loss and requirement for blood products were recorded. Results: The study
      groups showed no difference regarding baseline variables. One patient in the
      fibrinogen group (1.66%) and four patients in the control group (6.66%) received
      blood products (P < 0.05), and the blood drainage tube at 24 hours after
      operation was 36.50) 18.70 (mL in the fibrinogen group and 151.36) 120.58 (mL in
      the control group (P = 0.005). There were no differences in hemoglobin,
      hematocrit, PT, PTT, INR, and serum fibrinogen level between the groups at any
      time. Conclusions: The current study demonstrated that using fibrinogen in
      patients with high bleeding risk may effectively reduce the amount of bleeding
      and its subsequent blood transfusion requirement, after open prostatectomy
      surgery.

PMID- 30214887
TI  - The Effect of Chronic Consumption of Angiotensin-Converting Enzyme Inhibitors and
      Angiotensin Receptor Antagonists on Blood Pressure and Inotrope Consumption After
      Separation from Cardiopulmonary Bypass.
AB  - Background: Chronic use of renin-angiotensin system (RAS) antagonists
      (angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor
      antagonists (ARAS)) can cause hypotension during anesthesia. In some studies
      hemodynamic instability, including hypotension and its effects on the clinical
      outcome in patients treated with these drugs during coronary artery bypass graft
      (CABG) and need to excessive vasoactive drugs in these patient population, has
      been described. The aim of this study was to evaluate the effect of chronic
      consumption of ACEIs and ARAS on blood pressure and inotrope consumption during
      coronary artery bypass graft under cardiopulmonary bypass. Methods: A total of
      200 patients undergoing coronary artery bypass graft surgery, who were treated
      with either ARAS or ACEIs (n = 100) over at least 2 months, or who were not
      treated with any RAS antagonists (control group, n = 100) were enrolled. The mean
      arterial blood pressure, central venous pressure, and need for vasoactive drugs,
      were measured after induction of anesthesia (T1) before cardiopulmonary bypass
      (T2) and after separation from (CPB), (T3). Results: There were no significant
      differences regarding the mean arterial pressure (case group: T1: 84 +/- 7 mmHg,
      T2: 77 +/- 6 mmHg, T3: 83 +/- 8 mmHg), (control group: T1: 85 +/- 7 mmHg, T2: 81
      +/- 7 mmHg, T3:84 +/- 6 mmHg) between two groups (P > 0.05). Also there were no
      significant differences regarding mean central venous pressure, mean heart rate,
      and vasoactive drug consumption between the two groups during the time of
      intervals. Conclusions: We found that preoperative (RAS) antagonist's
      continuation have not profound hemodynamic changes during coronary artery bypass
      graft under cardiopulmonary bypass and so we conclude that omitting these drugs
      before surgery did not have a sufficient advantage to be recommended routinely.

PMID- 30214888
TI  - The Relationship between Arterial and Central Venous Blood Gases Values in
      Patients Undergoing Mechanical Ventilation after Cardiac Surgery.
AB  - Background: The most straightforward method of ascertaining arterial PO2, PCO2,
      and other components of blood gas is to measure them directly from a blood
      sample. In situations in which arterial puncture cannot be achieved or may be
      technically difficult, the venous blood sample can be used. Methods: In a
      prospective analytical study, 80 patients undergoing mechanical ventilation after
      open-heart surgery in the intensive care unit were evaluated. Simultaneous,
      matched arterial and central venous blood gas samples were taken from radial
      artery line and central vein, respectively, when the ABG (arterial blood gases)
      assessment was needed. Arterial and central venous blood samples were analyzed
      and data were expressed as mean and +/- SD. Results: The Pearson correlation
      coefficient for pH, PCO2, HCO3, and SatO2 was 0.898, 0.940, 0.840, and 0.567,
      respectively. There was a significant correlation between arterial and central
      venous values of pH, PCO2, and HCO3 (P < 0.0001). The mean difference between
      arterial and central venous PCO2 was -2.44 +/- 2.6 mmHg, and the mean venous pH
      value was only 0.021 +/- 0.037 units lower than the mean arterial value. In
      addition, the calculated mean bicarbonate concentration in venous blood was only
      about 0.06 +/- 1.5 mEq.L higher than the mean arterial value. Conclusions: The
      central venous PCO2, pH, and HCO3 measured during mechanical ventilation in the
      intensive care unit approximate arterial values closely enough to permit the
      estimation of the adequacy of ventilation and acid-base status. The central
      venous Sat O2 does not reliably parallel the arterial Sat O2. In conclusion,
      venous blood sampling can potentially reduce the requirement for ABG sampling in
      special situations.

PMID- 30214889
TI  - Propofol-Induced Masseter Muscle Spasm in a Woman with a Major Depressive
      Disorder.
AB  - Masseter muscle rigidity is a known complication of drugs such as succinylcholine
      and volatile agents. However, muscle rigidity is an uncommon complication of
      propofol. We report the case of a 56-year-old ASA-PS class I woman refereeing for
      colonoscopy due to chronic constipation under deep intravenous sedation. She
      suffered masseter spasm after the injection of propofol. Masseter spasm should
      not be considered limited to special drug groups. In any case of difficult mouth
      opening, masseter spasm should be kept in mind and deepening of anesthesia or
      complete blockade of neuromuscular junction should be considered by the use of
      non-depolarizing muscle relaxants.

PMID- 30214890
TI  - Letter to Editor: "A Comparative Study of the Amount of Bleeding and Hemodynamic
      Changes between Dexmedetomidine Infusion and Remifentanil Infusion for Controlled
      Hypotensive Anesthesia in Lumbar Discopathy Surgery; A Double-Blind, Randomized,
      Clinical Trial".

PMID- 30214891
TI  - The impact of genital psoriasis on quality of life: a systematic review.
AB  - Psoriasis is a chronic immune-mediated inflammatory disease with significant
      medical and psychological comorbidities. In addition to having increased
      cardiovascular risk and mortality, psoriasis patients are more likely to be
      depressed, anxious, and endorse suicidal ideation than the general population.
      These patients often have low self-esteem and feel stigmatized due to their skin
      disease, which can prevent them from pursuing relationships, dating, and
      attending social activities. Up to 63% of adult psoriasis patients experience
      psoriatic lesions on their genital area during their lifetime, but often do not
      discuss these issues with their physicians due to embarrassment, stigmatization,
      or shyness about this sensitive location. However, psoriasis in sensitive areas,
      such as the genitals, may result in quality of life impairment greater than that
      of patients with psoriasis elsewhere on their body, particularly in respect to
      romantic relationships, intimacy, and sexual function. This article evaluates the
      current literature regarding the impact of genital psoriasis on the quality of
      life of affected patients.

PMID- 30214892
TI  - Profile of tildrakizumab-asmn in the treatment of moderate-to-severe plaque
      psoriasis: evidence to date.
AB  - Plaque psoriasis is an immune-mediated skin disease that affects roughly 3% of
      adults in the United States. Advances over the past 20 years in understanding the
      immune-mediated pathophysiology of psoriasis have led to the development of
      targeted biologic therapies for this condition. Currently, biologic medications
      approved for the treatment of plaque psoriasis include tumor necrosis factor
      alpha inhibitors, interleukin (IL)-17 or IL-17 receptor inhibitors, IL-12/23
      inhibitors, and IL-23 inhibitors. Tildrakizumab-asmn is a monoclonal antibody
      that targets the p19 subunit of IL-23 and is approved for use in adult patients
      with moderate-to-severe plaque psoriasis who are candidates for systemic therapy
      or phototherapy. This article reviews the current pharmacologic, efficacy, and
      safety data on tildrakizumab-asmn.

PMID- 30214893
TI  - Role of a clinical pharmacist as part of a multidisciplinary care team in the
      treatment of HCV in patients living with HIV/HCV coinfection.
AB  - Background: The objective of the study was to evaluate the role of a clinical
      pharmacist in hepatitis C virus (HCV) treatment of patients living with HIV/HCV
      coinfection. Methods: We conducted a descriptive study to quantify the functions
      of a clinical pharmacist in HCV treatment of patients living with HIV/HCV
      coinfection who were initiating HCV treatment at a publicly funded clinic between
      March 18, 2015 and September 15, 2016. The clinical pharmacist's role was
      categorized into eight categories: 1) HCV prior authorization (PA) completion; 2)
      HCV medication adherence counseling; 3) HCV drug-drug interaction (DDI)
      counseling and screening; 4) HCV medication counseling regarding common adverse
      events (AEs); 5) HCV counseling regarding HCV treatment outcomes and risk of
      reinfection; 6) ordering laboratory tests and interpretation of HCV laboratory
      values; 7) HIV medication AE assessment; and 8) other (including refilling
      medications and management of other comorbidities). Results: One hundred and
      thirty-five patients initiated treatment during this timeframe: 77.0% were males,
      56.3% non-cirrhotic, 77.0% HCV treatment-naive, 45.9% HCV genotype 1a, and 83.0%
      initiated on ledipasvir/sofosbuvir. The clinical pharmacist completed 150 PAs,
      counseled on HCV medication adherence in 79.2% of patients, conducted HCV DDI
      counseling and screening in 54.2%, and monitored HCV medication AEs in 54.2%. The
      clinical pharmacist counseled patients on HCV treatment outcomes and risk of
      reinfection in 53.1%, ordered laboratory tests in 44.8%, and reported and
      interpreted laboratory values in 44.8%. The clinical pharmacist assessed HIV
      medication AEs in 54.2% of patients and participated in other activities in
      42.7%. Conclusion: A clinical pharmacist's expertise as part of a
      multidisciplinary care team facilitates optimal treatment outcomes and provides
      critical support in the management of DAA therapy in individuals living with
      HIV/HCV coinfection.

PMID- 30214894
TI  - The Pan-Cytokeratin Staining Intensity and Fractal Computational Analysis of
      Breast Tumor Malignant Growth Patterns Prognosticate the Occurrence of Distant
      Metastasis.
AB  - Improved prognosis of breast cancer outcome could prolong patient survival by
      reliable identification of patients at high risk of metastasis occurrence which
      could benefit from more aggressive treatments. Based on such clinical need, we
      prognostically evaluated the malignant cells in breast tumors, as the obvious
      potential source of unexploited prognostic information. The patient group was
      homogeneous, without any systemic treatments or lymph node spread, with smaller
      tumor size (pT1/2) and a long follow-up. Epithelial cells were labeled with
      AE1/AE3 pan-cytokeratin antibody cocktail and comprehensively analyzed.
      Monofractal and multifractal analyses were applied for quantification of
      distribution, shape, complexity and texture of malignant cell clusters, while
      mean pixel intensity and total area were measures of the pan-cytokeratin
      immunostaining intensity. The results surprisingly indicate that simple binary
      images and monofractal analysis provided better prognostic information then
      grayscale images and multifractal analysis. The key findings were that shapes and
      distribution of malignant cell clusters (by binary fractal dimension; AUC =
      0.29), their contour shapes (by outline fractal dimension; AUC = 0.31) and
      intensity of the pan-cytokeratin immunostaining (by mean pixel intensity; AUC =
      0.30) offered significant performance in metastasis risk prognostication. The
      results reveal an association between the lower pan-cytokeratin staining
      intensity and the high metastasis risk. Another interesting result was that
      multivariate analysis could confirm the prognostic independence only for fractal
      but not for immunostaining intensity features. The obtained results reveal
      several novel and unexpected findings highlighting the independent prognostic
      efficacy of malignant cell cluster distribution and contour shapes in breast
      tumors.

PMID- 30214895
TI  - Cancerous Protein Network That Inhibits the Tumor Suppressor Function of WW
      Domain-Containing Oxidoreductase (WWOX) by Aberrantly Expressed Molecules.
AB  - Recent findings indicate that the WW domain-containing oxidoreductase (WWOX) is a
      tumor suppressor protein that contains two N-terminal WW domains and a central
      short-chain dehydrogenase/reductase domain. WWOX protein mediates multiple
      signaling networks that suppress carcinogenesis through binding of its first WW
      domain to various cancer-associated proteins, i.e., p73, AP-2gamma, and others.
      Although the tumor suppressor property of WWOX is inarguable, WWOX is not
      inactivated in the manner characteristic of the canonical Knudson hypothesis.
      Impairment of both alleles of WWOX is thought to be a rare event, only occurring
      in a few cancer cell lines. How is the tumor suppressor function of WWOX impaired
      in cancer cells? Recent advances highlight that a small transmembrane protein
      possessing a PPxY motif, called TMEM207, and its relatives are aberrantly
      expressed in various cancer cells and hinder the tumor suppressor function of
      WWOX through inhibiting its WW domain. Here, we review the recent findings
      related to the pathobiological properties of TMEM207 and its relatives based on
      clinicopathological and experimental pathological studies.

PMID- 30214896
TI  - Detection and Phylogenetic Characterization of Anaplasma capra: An Emerging
      Pathogen in Sheep and Goats in China.
AB  - Anaplasma capra is an emerging pathogen, which can infect ruminants and humans.
      This study was conducted to determine the occurrence of A. capra in the blood
      samples of sheep and goats in China. Using nested polymerase chain reaction
      (nested-PCR) targeting the gltA gene and conventional PCR targeting the heat
      shock protein (groEL) gene and the major surface protein4 gene (msp4), A. capra
      was detected in 129 (8.9%) of 1453 sheep and goat blood samples. The positive
      rate was higher in goats (9.4%, 89/943) than in sheep (7.8%, 40/510) (chi2 =
      1.04, p > 0.05, df = 1). For sheep, A. capra was found in 17 sites from 2
      provinces. The prevalence was 28.6% in sheep from Liaoning province, which was
      higher than in Henan Province (7.3%). For goats, A. capra was detected in 35
      sites from 7 provinces. The prevalence varied from 0 to 19.4% in the goat sites
      examined. The prevalence rates were 19.4, 19.3, 10, 8.8, 6.8, 1.8, and 0% in
      goats from Guizhou province, Henan Province, Inner Mongolia Autonomous Region,
      Shanxi Province, Xinjiang Uygur Autonomous Region, Yunnan province, and Gansu
      province, respectively. Based on the analysis of the A. capra citrate synthase
      gene (gltA), two variants were identified. Variant I showed a high sequence
      similarity to the A. capra, which were previously reported in sheep, goats,
      Ixodes persulcatus, Haemaphysalis longicornis, Haemaphysalis qinghaiensis, and
      humans. Variant II was only found in Luoyang, Anyang, and Sanmengxia, of Henan
      province. To our knowledge, this is the first detection of this variant of A.
      capra in sheep and goat blood in China. Phylogenetic analysis based on groEL and
      msp4 genes showed that the Anaplasma sp. sequences clustered independently from
      A. capra and other Anaplasma species with high bootstrap values. We found A.
      capra DNA in sheep and goats in China, providing evidence that sheep and goats
      can be infected by A. capra. We also found that this zoonotic pathogen is widely
      distributed in China. This study provides information for assessing the public
      health risks for human anaplasmosis.

PMID- 30214897
TI  - Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow
      Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L)
      amazonensis Amastigotes-Hosted in Mouse CBA Macrophages.
AB  - The current long-term treatment for leishmaniasis causes severe side effects and
      resistance in some cases. An evaluation of the anti-leishmanial potential of an
      HSP90-inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), demonstrated
      its potent effect against Leishmania spp. in vitro and in vivo. We have
      previously shown that 17-AAG can kill L. (L) amazonensis promastigotes with an
      IC50 of 65 nM and intracellular amastigote at concentrations as low as 125 nM. As
      this compound presents low solubility and high toxicity in human clinical trials,
      we prepared an inclusion complex containing hydroxypropyl-beta-cyclodextrin and
      17-AAG (17-AAG:HPbetaCD) to improve its solubility. This complex was
      characterized by scanning electron microscopy, and X-ray diffraction. Liposomes
      containing 17-AAG:HPbetaCD was prepared and evaluated for encapsulation
      efficiency (EE%), particle size, polydispersity index (PDI), pH, and zeta
      potential, before and after accelerated and long-term stability testing. An
      evaluation of leishmanicidal activity against promastigotes and intracellular
      amastigotes of L. (L) amazonensis was also performed. The characterization
      techniques utilized confirmed the formation of the inclusion complex, HPbetaCD:17
      AAG, with a resulting 33-fold-enhancement in compound water solubility. Stability
      studies revealed that 17-AAG:HPbetaCD-loaded liposomes were smaller than 200 nm,
      with 99% EE. Stability testing detected no alterations in PDI that was 0.295, pH
      7.63, and zeta potential +22.6, suggesting liposome stability, and suitability
      for evaluating leishmanicidal activity. Treatment of infected macrophages with
      0.006 nM of 17-AAG:HPbetaCD or 17-AAG:HPbetaCD-loaded liposomes resulted in
      almost complete amastigote clearance inside macrophages after 48 h. This
      reduction is similar to the one observed in infected macrophages treated with 2
      MUM amphotericin B. Our results showed that nanotechnology and drug delivery
      systems could be used to increase the antileishmanial efficacy and potency of 17
      AAG in vitro, while also resulting in reduced toxicity that indicates these
      formulations may represent a potential therapeutic strategy against
      leishmaniasis.

PMID- 30214898
TI  - One Health Relationships Between Human, Animal, and Environmental Microbiomes: A
      Mini-Review.
AB  - The One Health concept stresses the ecological relationships between human,
      animal, and environmental health. Much of the One Health literature to date has
      examined the transfer of pathogens from animals (e.g., emerging zoonoses) and the
      environment to humans. The recent rapid development of technology to perform high
      throughput DNA sequencing has expanded this view to include the study of entire
      microbial communities. Applying the One Health approach to the microbiome allows
      for consideration of both pathogenic and non-pathogenic microbial transfer
      between humans, animals, and the environment. We review recent research studies
      of such transmission, the molecular and statistical methods being used, and the
      implications of such microbiome relationships for human health. Our review
      identified evidence that the environmental microbiome as well as the microbiome
      of animals in close contact can affect both the human microbiome and human health
      outcomes. Such microbiome transfer can take place in the household as well as the
      workplace setting. Urbanization of built environments leads to changes in the
      environmental microbiome which could be a factor in human health. While affected
      by environmental exposures, the human microbiome also can modulate the response
      to environmental factors through effects on metabolic and immune function. Better
      understanding of these microbiome interactions between humans, animals, and the
      shared environment will require continued development of improved statistical and
      ecological modeling approaches. Such enhanced understanding could lead to
      innovative interventions to prevent and manage a variety of human health and
      disease states.

PMID- 30214899
TI  - Vibrio cholerae Transmits Through Water Among the Household Contacts of Cholera
      Patients in Cholera Endemic Coastal Villages of Bangladesh, 2015-2016 (CHoBI7
      Trial).
AB  - Recurrent cholera causes significant morbidity and mortality in cholera endemic
      estuarine areas of Bangladesh. There have been limited studies to investigate the
      transmission patterns of V. cholerae associated with cholera in Bangladesh. In
      this study, we characterized V. cholerae serogroup O1 isolated from 30 cholera
      patients, 76 household contacts, 119 stored drinking water samples, and 119 water
      source samples in Bakerganj and Mathbaria, two cholera endemic coastal regions in
      Bangladesh. Results of phenotypic and molecular characterization of V. cholerae
      isolates (n = 56) confirmed them to be toxigenic belonging to serogroup O1
      biotype El Tor (ET), and possessing cholera toxin of the classical biotype
      (altered ET). Molecular fingerprinting of the V. cholerae O1 of clinical and
      water origins determined by PFGE of Not-I- digested genomic DNA showed them to be
      closely related, as the PFGE banding patterns were highly homogenous.
      Phylogenetic analysis using dendrogram of cholera patients, household contacts,
      and household groundwater sources showed isolates within households to be
      clonally linked, suggesting water as an important vehicle of transmission of
      cholera in the coastal villages of Bangladesh. Transmission of toxigenic V.
      cholerae O1 through drinking water in cholera endemic rural settings underscores
      the urgent need for evidence based water, sanitation, and hygiene interventions
      promoting safe drinking water to prevent morbidity and mortality related to
      cholera and other enteric infections in Bangladesh.

PMID- 30214900
TI  - Particle-Stabilized Fluid-Fluid Interfaces: The Impact of Core Composition on
      Interfacial Structure.
AB  - The encapsulation of small molecule drugs in nanomaterials has become an
      increasingly popular approach to the delivery of therapeutics. The use of
      emulsions as templates for the synthesis of drug impregnated nanomaterials is an
      exciting area of research, and a great deal of progress has been made in
      understanding the interfacial chemistry that is critical to controlling the
      physicochemical properties of both the encapsulated material and the templated
      material. For example, control of the interfacial tension between an oil and
      aqueous phase is a fundamental concern when designing drug delivery vehicles that
      are stabilized by particulate surfactants at the fluid interface. Particles in
      general are capable of self-assembly at a fluid interface, with a preference for
      one or the other of the phases, and much work has focussed on modification of the
      particle properties to optimize formation and stability of the emulsion. An issue
      arises however when a model, single oil system is translated into more complex,
      real-world scenarios, which are often multi-component, with the incorporation of
      charged active ingredients and other excipients. The result is potentially a huge
      change in the properties of the dispersed phase which can lead to a failure in
      the capability of particles to continue to stabilize the interface. In this mini
      review, we will focus on two encapsulation strategies based on the selective
      deposition of particles or proteins on a fluid-fluid interface: virus-like
      particles and polymer microcapsules formed from particle-stabilized emulsion
      templates. The similarity between these colloidal systems lies in the fact that
      particulate entities are used to stabilize fluid cores. We will focus on those
      studies that have described the effect of subtle changes in core composition on
      the self-assembly of particles at the fluid-fluid interface and how this
      influences the resulting capsule structure.

PMID- 30214901
TI  - Sun Exposure and Melanoma, Certainties and Weaknesses of the Present Knowledge.
AB  - Sun exposure is the main risk factor for cutaneous malignant melanoma (CMM).
      However, the UV-related pathogenetic mechanisms leading to CMM are far to be
      fully elucidated. In this paper we will focus on what we still don't fully know
      about the relationship between UVR and CMM. In particular, we will discuss: the
      action spectrum of human CMM, how different modalities of exposure (continuous/
      intermittent; erythemal/ suberythemal) relate to different CMM variants, the
      preferential UVR induced DNA mutations observed in different CMM variants, the
      role of UV-related and UV-unrelated genetic damages in the same melanoma cells.
      Moreover, we will debate the importance of UVA induced oxidative and anaerobic
      damages to DNA and other cell structures and the role of melanins, of modulation
      of innate and acquired immunity, of vitamin D and of chronic exposure to
      phototoxic drugs and other xenobiotics. A better understanding of these issues
      will help developing more effective preventative strategies and new therapeutic
      approaches.

PMID- 30214902
TI  - Ketogenic Ratio Determines Metabolic Effects of Macronutrients and Prevents
      Interpretive Bias.

PMID- 30214905
TI  - Variables Affecting Thigh Girth Measurement and Observer Reliability in Dogs.
AB  - Objective: The purpose of the study reported here was to describe variables
      affecting thigh girth measurements preoperatively and 2 weeks after surgical
      stabilization of the stifle and to examine inter- and intra-observer reliability.
      Animals: Ten hound-type dogs with experimental, unilateral, cranial cruciate
      ligament transection, and surgical stabilization. Procedures: Dogs were placed in
      lateral recumbency for measurements of thigh circumference after the stifle was
      placed in flexed (F), estimated standing (S), and extended (E) positions.
      Measurements were made at 50 and 70% of thigh length (TL), with hair unclipped
      and then clipped prior to surgery, before and 2 weeks after cruciate ligament
      transection and stifle stabilization, and with and without sedation. A spring
      tension measuring tape was used to determine thigh girth that allowed a
      consistent amount of end-tension to be applied to the tape. All measurements were
      made by two blinded individuals in triplicate, data were recorded for each set of
      measurements and the mean of the three measurements for each condition was used
      for analysis. Results: Thigh girth was significantly greater at the more proximal
      site of 50% TL (36.7 +/- 2.6 cm) when compared to the 70% TL (31.7 +/- 2.7 cm) (P
      = 0.001). Sedation did not significantly affect thigh girth at any stifle
      position at the 70% and 50% TL. Although there were no differences in thigh
      circumference between the flexion and standing positions at 50% TL (F 38.2 +/-
      2.8 cm, S 38.1 +/- 2.9 cm) and 70% TL (F 33.6 +/- 1.6 cm; S 33.6 +/- 1.8 cm),
      full extension of the stifle resulted in significantly less thigh girth (50% TL
      36.6 +/- 2.6 cm, P = 0.006; 70% TL 31.7 +/- 2.6 cm, P = 0.006). Significant
      decreases in thigh girth were seen after surgery in all limb positions at both
      measurement sites. The highest correlations between Observer 1 (OB1) and Observer
      2 (OB2) with least differences in measurements were with the stifle in the
      extended position. Agreement between two observers using standard measuring
      technique was significant at both the 50% (OB1: 34.10 +/- 2.93 cm, OB2: 34.08 +/-
      2.65 cm, P = 0.007, ICC = 0.984) and 70% (OB1: 29.89 +/- 2.43 cm, OB2: 30.04 +/-
      2.30 cm, P = 0.004, ICC = 0.981) TL positions with the stifle placed in extended
      position. Conclusion and Clinical Importance: Thigh girth measurement may be
      useful as an outcome measure when appropriate measuring technique is used. It is
      recommended that thigh girth be obtained at a distance of 70% thigh length, with
      the leg in an extended position while in lateral recumbency, and the dog relaxed
      or under sedation. Further studies should be performed in a variety of clinical
      situations.

PMID- 30214903
TI  - Systematic Analysis of Gene Expression Profiles Controlled by hnRNP Q and hnRNP
      R, Two Closely Related Human RNA Binding Proteins Implicated in mRNA Processing
      Mechanisms.
AB  - Heteregeneous ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins
      that take part in all processes that involve mRNA maturation. As a consequence,
      alterations of their homeostasis may lead to many complex pathological disorders,
      such as neurodegeneration and cancer. For many of these proteins, however, their
      exact function and cellular targets are still not very well known. Here, we
      focused the attention on two hnRNP family members, hnRNP Q and hnRNP R, that we
      previously found affecting TDP-43 activity both in Drosophila melanogaster and
      human neuronal cell line. Classification of these two human proteins as paralogs
      is suported by the high level of sequence homology and by the observation that in
      fly they correspond to the same protein, namely Syp. We profiled differentially
      expressed genes from RNA-Seq and generated functional enrichment results after
      silencing of hnRNP Q and hnRNP R in neuroblastoma SH-SY5Y cell line.
      Interestingly, despite their high sequence similarity, these two proteins were
      found to affect different cellular pathways, especially with regards to
      neurodegeneration, such as PENK, NGR3, RAB26, JAG1, as well as inflammatory
      response, such as TNF, ICAM1, ICAM5, and TNFRSF9. In conclusion, human hnRNP Q
      and hnRNP R may be considered potentially important regulators of neuronal
      homeostasis and their disruption could impair distinct pathways in the central
      nervous system axis, thus confirming the importance of their conservation during
      evolution.

PMID- 30214904
TI  - Percutaneous Coronary Intervention in Familial Hypercholesterolemia Is
      Understudied.
AB  - Familial hypercholesterolemia (FH) is a common heritable condition in which
      mutations of genes governing cholesterol metabolism result in elevated LDL levels
      and accelerated atherosclerosis. The treatment of FH focuses on lipid lowering
      drugs to decrease patients' cholesterol levels and reduce their risk of
      cardiovascular events. Even with optimal medical therapy, some FH patients will
      develop coronary atherosclerosis, suffer myocardial infarction, and require
      revascularization. Yet, the revascularization of FH patients has not been widely
      studied. Here we review FH, identify unanswered questions in the interventional
      management of FH patients, and explore barriers and opportunities for answering
      these questions. Further research is needed in this neglected but important topic
      in interventional cardiology.

PMID- 30214906
TI  - Left Atrial Appendage Occlusion Complicated by Appendage Perforation Rescued by
      Device Deployment.
AB  - The Watchman device is a transcatheter left atrial appendage (LAA) occluding
      device used in patients with nonvalvular atrial fibrillation (NVAF) and a high
      CHADS2-VA2SC score who are poor long-term anticoagulation candidates. Pericardial
      effusion related to device deployment and perforation can be a life-threatening
      complication. While not common in hands of experienced operators, management may
      require surgical intervention. Here we present a rare case of LAA perforation,
      which was corrected by successful repositioning of the device foregoing the need
      for surgical management.

PMID- 30214907
TI  - Patient-Specific 3-Dimensional Modeling and Its Use for Preoperative Counseling
      of Patients Undergoing Hip Arthroscopy.
AB  - Background: Femoroacetabular impingement (FAI) represents complex alterations in
      the bony morphology of the proximal femur and acetabulum. Imaging studies have
      become crucial in diagnosis and treatment planning for symptomatic FAI but also
      have limited patient understanding and satisfaction. Exploration of alternative
      patient counseling modalities holds promise for improved patient understanding,
      satisfaction, and ultimately for outcomes. Purpose: To compare perceived
      understanding of functional anatomy and FAI pathomorphology among patients
      counseled with routine computed tomography (CT), generic hip models, and a 3
      dimensional (3D) model printed in accordance with a patient's specific anatomy.
      Study Design: Cohort study; Level of evidence, 2. Methods: A prospective
      randomized analysis of patients presenting with radiographically confirmed FAI
      was conducted between November 2015 and April 2017. Patients were randomized into
      groups that received preoperative counseling with CT imaging alone, a generic
      human hip model, or a haptic 3D model of their hip. All groups were subjected to
      a novel questionnaire examining patient satisfaction and understanding on a
      variety of topics related to FAI. Data were compared with bivariate and
      multivariate analyses. Statistical significance was determined as P < .05.
      Results: Thirty-one patients were included in this study (25 men, 6 women). Ten
      patients were randomized to the CT-only group, 11 to the generic hip model group,
      and 10 to receive custom 3D-printed models of their hips. Patients preoperatively
      counseled with isolated CT imaging or a generic hip model reported greater
      understanding of their pathophysiology and the role of surgical intervention when
      compared with those counseled with haptic 3D models (P = .03). At final follow
      up, patients counseled with the use of isolated CT imaging or haptic 3D models
      reported greater increases and retention of understanding as compared with those
      counseled with generic hip models alone (P = .03). Conclusion: Preoperative
      counseling with haptic 3D hip models does not appear to favorably affect patient
      reported understanding or satisfaction with regard to FAI when compared with the
      use of CT imaging alone. Continued research into alternative counseling means may
      serve to further improve patient understanding and satisfaction on this complex
      anatomic phenomenon.

PMID- 30214908
TI  - Corneal collagen crosslinking in patients treated with dextran versus isotonic
      hydroxypropyl methylcellulose (HPMC) riboflavin solution: a retrospective
      analysis.
AB  - Background: Corneal collagen crosslinking (CXL) is a widely used treatment for
      halting the progression of keratoconus. Although initial studies of CXL were
      performed with a riboflavin solution containing dextran, recent protocols for CXL
      have indicated the use of a riboflavin solution containing isotonic hydroxypropyl
      methylcellulose (HPMC). This study was performed to investigate differences in
      visual outcomes and Scheimpflug (Pentacam) analysis in patients who have
      undergone epithelium-off CXL with riboflavin solution containing either 20%
      dextran versus 1.1% HPMC. Methods: All patients in this non-randomized, non
      masked, retrospective cohort analysis were treated at Edward S. Harkness Eye
      Institute, Columbia University Medical Center, New York, NY, USA. Thirty-seven
      eyes of 33 patients were crosslinked with a dextran solution and 19 eyes of 19
      patients crosslinked with an isotonic HPMC solution, both using an epithelium-off
      30-min, 3 mW/cm2 protocol. All patients had a diagnosis of keratoconus or post
      refractive surgery ectasia. Best spectacle corrected visual acuity (BSCVA) and
      Pentacam parameters were compared at all follow up visits (1, 6, 12, and 24
      months). Differences between groups treated with HPMC and dextran were compared
      using student's t-test. Differences between treated eye and fellow eye were
      calculated and compared between HPMC and dextran groups using paired t-test.
      Results: Patients treated with a dextran solution had significantly greater
      improvement in BSCVA at 1, 6, and 24 months (p < 0.05) compared to the isotonic
      HPMC-treated group. Kmax increased in both groups at 1 month; however, HPMC
      treated patients had a greater increase compared to dextran-treated patients (p =
      0.01). Kmax decreased in both groups at 6 and 12 months, although this finding
      was only significant in the HPMC-treated group at 12 months. Conclusions: Our
      data suggest that crosslinking with the dextran solution may result in
      significantly better visual outcomes (demonstrated by visual acuity) compared to
      the isotonic HPMC riboflavin solution. Dextran solutions may have other potential
      advantages intrinsic to its biochemical properties facilitating more efficient
      crosslinking. Further research and long-term evidence regarding the use of
      dextran versus HPMC riboflavin solutions in collagen crosslinking is necessary.

PMID- 30214909
TI  - Stone-Induced Purulent Choledocoduodenal Fistula Presenting with Ascending
      Cholangitis.
AB  - A biliary enteric fistula (BEF) is a rare, abnormal communication between any
      segment of the biliary tree with any portion of the small or large intestine. BEF
      is more frequently diagnosed with the increasingly widespread use of endoscopic
      retrograde cholangiopancreatography. Different theories have been postulated
      regarding the etiology of this fistula formation, with the most likely cause
      being gallstones. Treatment modalities, ranging from conservative management to
      surgical reconstruction, show varying levels of success. We present a case of BEF
      secondary to large common bile duct stones, successfully treated with endoscopic
      sphincterotomy (EST) followed by papillary balloon dilatation, and we briefly
      discuss large stone retrieval in the setting of atypical anatomy.

PMID- 30214910
TI  - Primary Pancreatic Chondrosarcoma.

PMID- 30214911
TI  - Cholesterol Crystal Embolization to the Kidney and to a Duodenal Leiomyoma.
AB  - Cholesterol crystal embolism can be spontaneous or iatrogenic, and it can involve
      any organ of the gastrointestinal tract, presenting with common gastrointestinal
      symptoms such as bleeding, perforation, obstruction, and inflammation. It is
      therefore considered the "great masquerader," requiring a high level of suspicion
      because the condition is associated with increased morbidity and mortality. We
      present a 69-year-old man who presented with gastrointestinal bleeding and
      azotemia. He was found to have cholesterol crystal embolization in the kidney and
      a duodenal leiomyoma, the latter being an uncommon site to embolize.

PMID- 30214913
TI  - A New Anthropomorphic Pediatric Spine Phantom for Proton Therapy Clinical Trial
      Credentialing.
AB  - Purpose: To design and evaluate an anthropomorphic spine phantom for use in
      credentialing proton therapy facilities for clinical trial participation by the
      Imaging and Radiation Oncology Core Houston QA Center. Materials and Methods: A
      phantom was designed to perform an end-to-end audit of the proton spine treatment
      process, including simulation, dose calculation, and proton treatment delivery.
      Because plastics that simulate bone in proton beams are unknown, 11 potential
      materials were tested to identify suitable phantom materials. Once built,
      preliminary testing using passive scattering and spot scanning treatment plans
      (including a field junction) were created in-house and delivered 3 times to test
      reproducibility. The following measured attributes were compared with the
      calculated values: absolute dose agreement using thermoluminescent dosimeters,
      planar gamma agreement, distal range, junction match, and right and left profile
      alignment using radiochromic film. Finally, credentialing results from 10
      institutions were also assessed. Results: A suitable bone substitute was
      identified (Techtron HPV Bearing Grade), which had a measured relative stopping
      power that agreed within 1.1% of its value calculated by Eclipse. In-house
      passive scatter testing of the phantom demonstrated that the phantom was suitable
      for assessing craniospinal irradiation dose delivery. However, the in-house
      scanning beam results were more mixed, highlighting challenges in treatment
      delivery. Seven of ten institutions passed the proposed criteria for this
      phantom, a pass rate consistent with other Imaging and Radiation Oncology
      phantoms. Conclusions: An anthropomorphic proton spine phantom was developed to
      evaluate proton therapy delivery. This phantom provides a realistic challenge for
      centers wishing to participate in proton clinical trials and highlights the need
      for caution in applying advanced treatments.

PMID- 30214912
TI  - Cardiac Microvascular Dysfunction in Women Living With HIV Is Associated With
      Cytomegalovirus Immunoglobulin G.
AB  - Background: People living with HIV (PLWH) appear to be at increased risk of
      cardiovascular disease (CVD), and this is possibly more pronounced in women
      living with HIV (WLWH). In the general population, men are more likely to develop
      obstructive coronary artery disease (CAD), and women often present with a
      nonobstructive pattern with cardiac microvascular dysfunction. We investigated
      cardiac microvascular function in men and women living with HIV and tested for
      association with cytomegalovirus (CMV) immunoglobulin G (IgG), as this has been
      associated with CVD in PLWH. Methods: In a cross-sectional study, 94 PLWH on
      antiretroviral therapy were scanned with 82Rb positron emission
      tomography/computed tomography at rest and during adenosine-induced stress, which
      enables the quantification of the myocardial flow reserve (MFR). CMV IgG was
      measured in plasma. Results: WLWH had significantly lower MFR compared with men
      living with HIV (MLWH; P = .003), and >45% of the women had an MFR indicative of
      cardiac microvascular dysfunction, whereas this was only true for 24% of men (P =
      .03). CMV IgG concentrations were inversely associated with MFR among WLWH but
      not MLWH (P = .05 for interaction). Conclusions: In this first study comparing
      MFR in women and men living with HIV, we found that WLWH had significantly lower
      MFR than MLWH and 45% of the women had cardiac microvascular dysfunction despite
      younger age and lower cardiovascular risk. Furthermore, CMV IgG was inversely
      associated with MFR among women but not men. This calls for attention to CVD
      among young WLWH even with low cardiovascular risk.

PMID- 30214914
TI  - Random Insertional Mutagenesis of a Serotype 2 Dengue Virus Clone.
AB  - Protein tagging is a powerful method of investigating protein function. However,
      modifying positive-strand RNA virus proteins in the context of viral infection
      can be particularly difficult as their compact genomes and multifunctional
      proteins mean even small changes can inactivate or attenuate the virus. Although
      targeted approaches to functionally tag viral proteins have been successful,
      these approaches are time consuming and inefficient. A strategy that has been
      successfully applied to several RNA viruses is whole-genome transposon
      insertional mutagenesis. A library of viral genomes, each containing a single
      randomly placed small insertion, is selected by passaging in cell culture and the
      insertion sites can be identified using Next Generation Sequencing (NGS). Here we
      describe a protocol for transposon mutagenesis of the 16681 strain of dengue
      virus, serotype 2. Mutant dengue virus libraries containing short randomly placed
      insertions are passaged through mammalian cells and insertions are mapped by NGS
      of the viable progeny. The protocol is divided into four stages: transposon
      mutagenesis of a dengue cDNA clone, viral genome transfection into permissive
      cells, isolation of viral progeny genomes, and sequencing library preparation.

PMID- 30214917
TI  - A New Era in Pathology Consultation: The MyPathologist Electronic Consultation
      Tool.
AB  - Pathologists and laboratory scientists provide valuable guidance on laboratory
      utilization, test ordering, interpretation, and quality control provided that
      clinical staff can easily access the laboratory team. To encourage consultation
      between clinicians with laboratory scientists and pathologists, we developed an
      easily accessible electronic tool termed "MyPathologist," placed on the homepage
      of our electronic health record system. Over its 2-year pilot, utilization of
      this consultation tool climbed as we continued to publicize it and incorporated
      education into housestaff onboarding and electronic health record training.
      Physician satisfaction with the tool was high. Additionally, this became the
      primary source of consults to our residency call service. Evaluation of
      MyPathologist questions received during its pilot period showed that more than
      half the questions were of significant educational value to the residents, often
      focusing on results interpretation, appropriate test ordering, and quality
      control. MyPathologist is a novel electronic tool for pathology consultation
      within our electronic health record and also represents an avenue for educating
      residents, improving utilization of the laboratory, and improving patient care.

PMID- 30214915
TI  - Quantitative and Qualitative Assessment Methods for Biofilm Growth: A Mini
      review.
AB  - Biofilms are microbial communities attached to a surface and embedded in an
      extracellular polymeric substance which provides for the protection, stability
      and nutrients of the various bacterial species indwelling. These communities can
      build up in a variety of different environments from industrial equipment to
      medical devices resulting in damage, loss of productivity and disease. They also
      have great potential for economic and societal benefits as bioremediation agents
      and renewable energy sources. The great potential benefits and threats of
      biofilms has encouraged researchers across disciplines to study biofilm
      characteristics and antibiofilm strategies resulting in chemists, physicists,
      material scientists, and engineers, to develop beneficial biofilm applications
      and prevention methods. The ultimate outcome is a wealth of knowledge and
      innovative technology. However, without extensive formal training in microbes and
      biofilm research, these scientists find a daunting array of established
      techniques for growing, quantifying and characterizing biofilms while trying to
      design experiments and develop innovative laboratory protocols. This mini-review
      focuses on enriching interdisciplinary efforts and understanding by overviewing a
      variety of quantitative and qualitative biofilm characterization methods to
      assist the novice researcher in assay selection. This review consists of four
      parts. Part 1 is a brief overview of biofilms and the unique properties that
      demand a highly interdisciplinary approach. Part 2 describes the classical
      quantification techniques including colony forming unit (CFU) counting and
      crystal violet staining, but also introduces some modern methods including ATP
      bioluminescence and quartz crystal microbalance. Part 3 focuses on the
      characterization of biofilm morphology and chemistry including scanning electron
      microscopy and spectroscopic methods. Finally, Part 4 illustrates the use of
      software, including ImageJ and predictive modeling platforms, for biofilm
      analysis. Each section highlights the most common methods, including literature
      references, to help novice biofilm researchers make choices which commensurate
      with their study goals, budget and available equipment.

PMID- 30214919
TI  - Editor's Letter.

PMID- 30214918
TI  - Educational Case: Immune-Related Disorders of the Bowel: Celiac Disease.
AB  - The following fictional case is intended as a learning tool within the Pathology
      Competencies for Medical Education (PCME), a set of national standards for
      teaching pathology. These are divided into three basic competencies: Disease
      Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and
      Therapeutic Pathology. For additional information, and a full list of learning
      objectives for all three competencies, see
      http://journals.sagepub.com/doi/10.1177/2374289517715040.

PMID- 30214916
TI  - Status and Future Directions of Preclinical Behavioral Pharmacology in Tobacco
      Regulatory Science.
AB  - Behavioral pharmacology is a branch of the experimental analysis of behavior that
      has had great influence in drug addiction research and policy. This paper
      provides an overview of recent behavioral pharmacology research in the field of
      tobacco regulatory science, which provides the scientific foundation for the Food
      and Drug Administration Center for Tobacco Products (FDA CTP) to set tobacco
      control policies. The rationale and aims of tobacco regulatory science are
      provided, including the types of preclinical operant behavioral models it deems
      important for assessing the abuse liability of tobacco products and their
      constituents. We then review literature relevant to key regulatory actions being
      considered by the FDA CTP, including regulations over nicotine and menthol
      content of cigarettes, and conclude with suggesting some directions for future
      research. The current era of tobacco regulatory science provides great
      opportunities for behavioral pharmacologists to address the leading cause of
      preventable death and disease worldwide.

PMID- 30214920
TI  - Ascribed Meaning of Disease Control: Perspectives of Patients With Type 2
      Diabetes.
AB  - Background: Contemporary treatment of type 2 diabetes mellitus (hereafter
      diabetes) heavily emphasizes "diabetes control," largely defined by measurable
      blood glucose parameters. Little is known about how people living with the
      condition themselves define diabetes control within the lived experience of their
      disease. Methods: As part of a qualitative study investigating the subjective
      construction of diabetes, 83 in-depth interviews were conducted with African
      American and non-Hispanic white older adults. Using content analysis, 4237 pages
      of narrative data were analyzed to explore how informants conceptualized diabetes
      control. Findings: Four themes emerged from the data, describing varied
      understandings of diabetes control: (a) blood sugar regulation, (b) practicable
      treatment adherence, (c) bodily experience, and (d) degree of pharmaceutical
      need. Findings demonstrate that among persons with diabetes, the term diabetes
      control is multifaceted. Conclusion: While clinical guidelines have established
      target blood glucose parameters as the standard indicator of diabetes control,
      persons with diabetes conveyed varied and diverse meanings situated within
      personal experiences. To foster empathetic and collaborative care, health-care
      providers tending to this population may consider integrating the emergent themes
      into communicative and treatment approaches.

PMID- 30214922
TI  - Deserve's Got Nothin' to Do With It: A Philosopher Visits the NICU.
AB  - After the death of my daughter Zoe in neonatal intensive care unit (NICU), a
      colleague asked me whether my status as an academic philosopher changed my
      experience in the NICU. In this short narrative, I outline 5 ways in which
      philosophical perspective helped me understand and cope with our hospital
      experience.

PMID- 30214921
TI  - Use of Visual Decision Aids in Physician-Patient Communication: A Pilot
      Investigation.
AB  - Introduction: A risk calculator paired with a personalized decision aid (RC&DA)
      may foster shared decision-making in primary care. We assessed the feasibility of
      using an RC&DA with patients in a primary care outpatient clinic and patients'
      experiences regarding communication and decision-making. Methods: This pilot
      study was conducted with 15 patients of 3 primary care physicians at a clinic
      within a tertiary medical center. An atherosclerotic cardiovascular disease
      (ASCVD) risk calculator was used to generate a personalized RC&DA that displayed
      absolute 10-year risk information as an icon array graphic. Patient perceptions
      of utility of the RC&DA, preferences for decision-making, and uncertainty with
      risk reduction decisions were measured with a semi-structured interview. Results:
      Patients reported that the RC&DA was easy to understand and knowledge gained was
      useful to modify their ASCVD risk. Patients used the RC&DA to make decisions and
      reported low uncertainty with those decisions. Conclusions: Our findings
      demonstrate the feasibility of, and positive patient experiences related to
      using, an RC&DA to facilitate shared decision-making between physicians and
      patients in an outpatient primary care setting.

PMID- 30214924
TI  - Just for Today.

PMID- 30214923
TI  - Creating Naptime: An Overnight, Nonpharmacologic Intensive Care Unit Sleep
      Promotion Protocol.
AB  - Introduction: Patients in the intensive care unit (ICU) have significantly
      disrupted sleep. Sleep disruption is believed to contribute to ICU delirium, and
      ICU delirium is associated with increased mortality. Experts recommend sleep
      promotion as a means of preventing or shortening the duration of delirium. ICU
      Sleep promotion protocols are highly complex and difficult to implement. Our
      objective is to describe the development, pilot implementation, and revision of a
      medical ICU sleep promotion protocol. Methods: Naptime is a clustered-care
      intervention that provides a rest period between 00:00 and 04:00. We used
      literature review, medical chart review, and stakeholder interviews to identify
      sources of overnight patient disturbance. With stakeholder input, we developed an
      initial protocol that we piloted on a small scale. Then, using protocol
      monitoring and stakeholder feedback, we revised Naptime and adapted it for
      unitwide implementation. Results: We identified sound, patient care, and patient
      anxiety as important sources of overnight disturbance. The pilot protocol altered
      the timing of routine care with a focus on medications and laboratory draws.
      During the pilot, there were frequent protocol violations for laboratory draws
      and for urgent care. Stakeholder feedback supported revision of the protocol with
      a focus on providing 60- to 120-minute rest periods interrupted by brief clusters
      of care between 00:00 and 04:00. Discussion: Four-hour blocks of rest may not be
      possible for all medical ICU patients, but interruptions can be minimized to a
      significant degree. Involvement of all stakeholders and frequent protocol
      reevaluation are needed for successful adoption of an overnight rest period.

PMID- 30214925
TI  - Patient Experience and Satisfaction With Acceptance and Commitment Therapy
      Delivered in a Complimentary Open Group Format for Adults With Eating Disorders.
AB  - We examined patient experiences and satisfaction with acceptance and commitment
      therapy (ACT) delivered in a novel weekly open-group therapy format immediately
      following psychiatric intake assessment into a hospital-based outpatient adult
      eating disorders program. Participants were 68 adults with a Diagnostic and
      Statistical Manual of Mental Disorders, 5th edition diagnosis of an eating
      disorder who reported their experiences and satisfaction with the ACT group.
      Participants reported that they were somewhat satisfied to very satisfied with
      the open ACT group and that the treatment content was helpful. Specifically,
      participants reported that ACT group helped them to recognize their personal
      values and learn strategies for behavior change. Satisfaction with ACT group was
      associated with engagement in the broader group therapy program. Results suggest
      that ACT delivered in an open group format is well liked by adults in an
      outpatient program for eating disorders. ACT is a promising complimentary
      treatment for individuals with eating disorders that can be easily integrated by
      clinicians into outpatient care.

PMID- 30214926
TI  - Challenges to Care and Medication Adherence of Patients With Chronic Myeloid
      Leukemia in a Resource Limited Setting: A Qualitative Study.
AB  - The factors related to care of patients with chronic myeloid leukemia (CML) often
      affects treatment outcome. We examined adherence to medication and other
      challenges to care in our patients on treatment of CML. This qualitative study
      involved in-depth interviews of 20 patients with CML receiving free imatinib
      (Glivec) from the Glivec International Patients' Assistance Program. Data
      collected were thematically analyzed. Findings revealed that despite free drug
      assistance, there was relative lack of awareness resulting in inappropriate
      health-seeking behavior. The challenges cut across situations such as poverty,
      fear of the sustenance of the compassionate drug program, and living far away
      from the clinic. Forgetfulness was reported as the cause of poor adherence in
      this study. Suggested solutions include increasing community awareness, ensuring
      sustainability of the program and establishing more treatment centers nationwide.
      Strategies such as reminders and patents' support will improve drug adherence
      among this cohort.

PMID- 30214928
TI  - Willingness to Pay for Teledermoscopy Services at a University Health Center.
AB  - Background: The study objective was to investigate the willingness to pay (WTP)
      for teledermoscopy services among students at a university health center. The
      hypothesis was that WTP for teledermoscopy among students would exceed the costs
      for traditional consultation. Methods: Between November 2013 and May 2014,
      students at a university health center were surveyed for their perceptions of
      teledermoscopy. One set of responses was collected from students visiting the
      health center for any reason (anonymous sample). An additional set of responses
      was collected from students visiting for dermatologic lesions (in-person sample).
      A contingent valuation method with a maximum likelihood estimation procedure was
      used to estimate the WTP distribution. Results: A total of 214 surveys were
      collected for the anonymous sample and 41 responses for the in-person sample. The
      mean (standard deviation [SD]) WTP for the anonymous sample was $55.27 ($39.11;
      95% confidence interval [CI]: $49.99-$60.55). The mean (SD) WTP for the in-person
      sample was $52.37 ($26.56; 95% CI: $43.99-$60.75). Median WTP for the 2 samples
      was similar: $48.84 and $48.01. Conclusions: We conclude that students would be
      willing to pay for teledermoscopy services that would provide the potential for
      significant system cost savings. This may be especially true in college health or
      similar settings where dermatology services may not be available.

PMID- 30214927
TI  - Codesigning a Measure of Person-Centred Coordinated Care to Capture the
      Experience of the Patient: The Development of the P3CEQ.
AB  - Background: Person-centred coordinated care (P3C) is a priority for stakeholders
      (ie, patients, carers, professionals, policy makers). As a part of the
      development of an evaluation framework for P3C, we set out to identify patient
      reported experience measures (PREMs) suitable for routine measurement and
      feedback during the development of services. Methods: A rapid review of the
      literature was undertaken to identity existing PREMs suitable for the probing
      person-centred and/or coordinated care. Of 74 measures identified, 7 met our
      inclusion criteria. We critically examined these against core domains and
      subdomains of P3C. Measures were then presented to stakeholders in codesign
      workshops to explore acceptability, utility, and their strengths/weaknesses.
      Results: The Long-Term Condition 6 questionnaire was preferred for its short
      length, utility, and tone. However, it lacked key questions in each core domain,
      and in response to requests from our codesign group, new questions were added to
      cover consideration as a whole person, coordination, care plans, carer
      involvement, and a single coordinator. Cognitive interviews, on-going codesign,
      and mapping to core P3C domains resulted in the refinement of the questionnaire
      to 11 items with 1 trigger question. The 11-item modified version was renamed the
      P3C Experiences Questionnaire. Conclusions: Due to a dearth of brief measures
      available to capture people's experience of P3C for routine practice, an existing
      measure was modified using an iterative process of adaption and validation
      through codesign workshops. Next steps include psychometric validation and
      modification for people with dementia and learning difficulties.

PMID- 30214929
TI  - Naive Expectations to Resignation: A Comparison of Life Descriptions of Newly
      Diagnosed Versus Chronic Persons Living With Stage D HF.
AB  - Purpose: This study examined life descriptions of persons with stage D heart
      failure (HF) comparing those newly diagnosed to those with chronic HF. Methods: A
      secondary analysis of interviews from 75 participants followed in a longitudinal
      study of persons with stage D HF was thematically analyzed. There were 24
      participants who were recently diagnosed with stage D HF (less than 2 years) and
      51 participants with HF longer than 2 years. Results: Both groups shared life
      descriptions along a continuum, where recently diagnosed participants described
      naive expectations with hope for improvement, while the chronic group appeared
      resigned to their fate and the reality of the limitations of living with HF. Four
      themes illustrated differences between the groups: outlook on life, activity
      adjustments, understanding of HF, and mood. Conclusions: Although persons with
      stage D HF share the same life descriptions, they have differing perspectives of
      life with HF. Findings from this study can help health-care providers tailor
      interventions based on the length of time from diagnosis.

PMID- 30214930
TI  - Satisfaction With Health Care Among Patients Navigated for Preventive Cancer
      Screening.
AB  - Background: Patient navigation (PN) programs can improve cancer screening in
      underserved populations. PN may advance quality and equity of care by supporting
      individuals at increased risk of not receiving recommended care. Objective: To
      evaluate patient satisfaction with medical care and PN for cancer screening.
      Methods: We conducted a telephone survey of patients enrolled in a randomized
      control trial evaluating the impact of PN for cancer screening to assess their
      satisfaction with overall medical care and the PN program. We measured patient
      satisfaction with medical care using the Patient Satisfaction Questionnaire-18
      and evaluated patient satisfaction with PN in the navigated group using the
      Patient Satisfaction with Interpersonal Relationships with Navigator
      questionnaire. Key Results: Satisfaction surveys were completed by 114 navigated
      and 108 non-navigated patients (33% response rate). Patients who received PN had
      higher satisfaction scores with overall medical care (71.0 vs 66.8; P < .001).
      Conclusions: Our findings show that patients at high risk of nonadherence with
      comprehensive cancer screening were satisfied with PN and suggest that PN could
      positively influence patient satisfaction with overall medical care.

PMID- 30214931
TI  - Patient-Centered Communication Behaviors That Correlate With Higher Patient
      Satisfaction Scores.
AB  - Background: With increased emphasis on improving the patient experience,
      clinicians are being asked to improve their patient-centered communication
      behaviors to improve patient satisfaction (PS) scores. Local Problem: The
      relationship between clinician communication behaviors and PS is poorly studied
      in the emergency department (ED) setting. The purpose of this study was to
      identify whether specific communication behaviors correlate with higher PS scores
      in the ED setting. Methods: During a quality improvement project, we performed
      191 bedside observations of ED clinicians during their initial interaction with
      patients and recorded the frequency of 8 positive communication behaviors as
      defined by the PatientSET tool. Interventions: The frequency of use of the
      PatientSET communication behaviors was compared between known high performers in
      Press Ganey PS scores versus low performers. Results: Being a high Press Ganey
      performer was associated with a significantly higher frequency of performance in
      6 of the 8 PatientSET communication behaviors. Conclusions: Positive
      communication behaviors such as those in the PatientSET tool occurred more
      frequently in ED clinicians with higher PS scores.

PMID- 30214932
TI  - Patients and Providers Are Amenable to Fecal Immunochemical Testing by Digital
      Rectal Exam.
AB  - Fecal immunochemical testing (FIT) for colorectal cancer (CRC) requires patients
      to return samples for processing, after having a spontaneously passed stool at
      home. This results in low completion rates (only 50% in our institution). Using
      stool obtained during an office-based digital rectal exam (DRE-FIT) could improve
      compliance, but it is not known whether patients and providers would find this
      option acceptable. Surveys were given to 100 physicians and 118 patients at our
      institution. We found that 68% of patients and 88% of providers approved of DRE
      FIT making this a potentially effective way to improve CRC screening compliance.

PMID- 30214933
TI  - Nitrogen isotope signature evidences ammonium deprotonation as a common transport
      mechanism for the AMT-Mep-Rh protein superfamily.
AB  - Ammonium is an important nitrogen (N) source for living organisms, a key
      metabolite for pH control, and a potent cytotoxic compound. Ammonium is
      transported by the widespread AMT-Mep-Rh membrane proteins, and despite their
      significance in physiological processes, the nature of substrate translocation
      (NH3/NH4+) by the distinct members of this family is still a matter of
      controversy. Using Saccharomyces cerevisiae cells expressing representative AMT
      Mep-Rh ammonium carriers and taking advantage of the natural chemical-physical
      property of the N isotopic signature linked to NH4+/NH3 conversion, this study
      shows that only cells expressing AMT-Mep-Rh proteins were depleted in 15N
      relative to 14N when compared to the external ammonium source. We observed 15N
      depletion over a wide range of external pH, indicating its independence of NH3
      formation in solution. On the basis of inhibitor studies, ammonium transport by
      nonspecific cation channels did not show isotope fractionation but competition
      with K+. We propose that kinetic N isotope fractionation is a common feature of
      AMT-Mep-Rh-type proteins, which favor 14N over 15N, owing to the dissociation of
      NH4+ into NH3 + H+ in the protein, leading to 15N depletion in the cell and
      allowing NH3 passage or NH3/H+ cotransport. This deprotonation mechanism explains
      these proteins' essential functions in environments under a low NH4+/K+ ratio,
      allowing organisms to specifically scavenge NH4+. We show that 15N isotope
      fractionation may be used in vivo not only to determine the molecular species
      being transported by ammonium transport proteins, but also to track ammonium
      toxicity and associated amino acids excretion.

PMID- 30214935
TI  - Inconsistencies undermine the conclusion that agriculture is a dominant source of
      NO x in California.
AB  - Almaraz et al. reported that agricultural soils are a dominant source of NO x
      pollution in California (20 to 32% of total statewide NO x emissions). However,
      this conclusion may be undermined by the lack of agreement between their modeled
      estimates and previously reported empirical measurements, the extrapolation of NO
      x fluxes during hot moments to derive annual estimates, and the overestimation of
      nitrogen fertilizer consumption in California.

PMID- 30214934
TI  - Frustration-induced phases in migrating cell clusters.
AB  - Certain malignant cancer cells form clusters in a chemoattractant gradient, which
      can spontaneously show three different phases of motion: translational,
      rotational, and random. Guided by our experiments on the motion of two
      dimensional clusters in vitro, we developed an agent-based model in which the
      cells form a cohesive cluster due to attractive and alignment interactions. We
      find that when cells at the cluster rim are more motile, all three phases of
      motion coexist, in agreement with our observations. Using the model, we show that
      the transitions between different phases are driven by competition between an
      ordered rim and a disordered core accompanied by the creation and annihilation of
      topological defects in the velocity field. The model makes specific predictions,
      which we verify with our experimental data. Our results suggest that
      heterogeneous behavior of individuals, based on local environment, can lead to
      novel, experimentally observed phases of collective motion.

PMID- 30214936
TI  - Learning of spatiotemporal patterns in a spiking neural network with resistive
      switching synapses.
AB  - The human brain is a complex integrated spatiotemporal system, where space (which
      neuron fires) and time (when a neuron fires) both carry information to be
      processed by cognitive functions. To parallel the energy efficiency and computing
      functionality of the brain, methodologies operating over both the space and time
      domains are thus essential. Implementing spatiotemporal functions within
      nanoscale devices capable of synaptic plasticity would contribute a significant
      step toward constructing a large-scale neuromorphic system that emulates the
      computing and energy performances of the human brain. We present a neuromorphic
      approach to brain-like spatiotemporal computing using resistive switching
      synapses. To process the spatiotemporal spike pattern, time-coded spikes are
      reshaped into exponentially decaying signals that are fed to a McCulloch-Pitts
      neuron. Recognition of spike sequences is demonstrated after supervised training
      of a multiple-neuron network with resistive switching synapses. Finally, we show
      that, due to the sensitivity to precise spike timing, the spatiotemporal neural
      network is able to mimic the sound azimuth detection of the human brain.

PMID- 30214937
TI  - GLK-IKKbeta signaling induces dimerization and translocation of the AhR-RORgammat
      complex in IL-17A induction and autoimmune disease.
AB  - Retinoic-acid-receptor-related orphan nuclear receptor gammat (RORgammat)
      controls the transcription of interleukin-17A (IL-17A), which plays critical
      roles in the pathogenesis of autoimmune diseases. Severity of several human
      autoimmune diseases is correlated with frequencies of germinal center kinase-like
      kinase (GLK) (also known as MAP4K3)-overexpressing T cells; however, the
      mechanism of GLK overexpression-induced autoimmunity remains unclear. We report
      the signal transduction converging on aryl hydrocarbon receptor (AhR)-RORgammat
      interaction to activate transcription of the IL-17A gene in T cells. T cell
      specific GLK transgenic mice spontaneously developed autoimmune diseases with
      selective induction of IL-17A in T cells. In GLK transgenic T cells, protein
      kinase Ctheta (PKCtheta) phosphorylated AhR at Ser36 and induced AhR nuclear
      translocation. AhR also interacted with RORgammat and transported RORgammat into
      the nucleus. IKKbeta (inhibitor of nuclear factor kappaB kinase beta)-mediated
      RORgammat Ser489 phosphorylation induced the AhR-RORgammat interaction. T cell
      receptor (TCR) signaling also induced the novel RORgammat phosphorylation and
      subsequent AhR-RORgammat interaction. Collectively, TCR signaling or GLK
      overexpression induces IL-17A transcription through the IKKbeta-mediated
      RORgammat phosphorylation and the AhR-RORgammat interaction in T cells. Our
      findings suggest that inhibitors of GLK or the AhR-RORgammat complex could be
      used as IL-17A-blocking agents for IL-17A-mediated autoimmune diseases.

PMID- 30214938
TI  - Early Holocene human presence in Madagascar evidenced by exploitation of avian
      megafauna.
AB  - Previous research suggests that people first arrived on Madagascar by ~2500 years
      before present (years B.P.). This hypothesis is consistent with butchery marks on
      extinct lemur bones from ~2400 years B.P. and perhaps with archaeological
      evidence of human presence from ~4000 years B.P. We report >10,500-year-old human
      modified bones for the extinct elephant birds Aepyornis and Mullerornis, which
      show perimortem chop marks, cut marks, and depression fractures consistent with
      immobilization and dismemberment. Our evidence for anthropogenic perimortem
      modification of directly dated bones represents the earliest indication of humans
      in Madagascar, predating all other archaeological and genetic evidence by >6000
      years and changing our understanding of the history of human colonization of
      Madagascar. This revision of Madagascar's prehistory suggests prolonged human
      faunal coexistence with limited biodiversity loss.

PMID- 30214941
TI  - Extrapolation of point measurements and fertilizer-only emission factors cannot
      capture statewide soil NO x emissions.
AB  - Maaz et al. argue that inconsistencies across scales of observation undermine our
      working hypothesis that soil NO x emissions have been substantially overlooked in
      California; however, the core issues they raise are already discussed in our
      manuscript. We agree that point measurements cannot be reliably used to estimate
      statewide soil NO x emissions-the principal motivation behind our new
      modeling/airplane approach. Maaz et al.'s presentation of fertilizer-based
      emission factors (a nonmechanistic scaling of point measures to regions based
      solely on estimated nitrogen fertilizer application rates) includes no data from
      California or other semiarid sites, and does not explicitly account for widely
      known controls of climate, soil, and moisture on soil NO x fluxes. In contrast,
      our model includes all of these factors. Finally, the fertilizer sales data that
      Maaz et al. highlight are known to suffer from serious errors and do not offer a
      logically more robust pathway for spatial analysis of NO x emissions from soil.

PMID- 30214940
TI  - A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa,
      reveals a hyperdiverse hymenopteran toxin gene family.
AB  - Ants (Hymenoptera: Formicidae) are diverse and ubiquitous, and their ability to
      sting is familiar to many of us. However, their venoms remain largely unstudied.
      We provide the first comprehensive characterization of a polypeptidic ant venom,
      that of the giant red bull ant, Myrmecia gulosa. We reveal a suite of novel
      peptides with a range of posttranslational modifications, including disulfide
      bond formation, dimerization, and glycosylation. One venom peptide has sequence
      features consistent with an epidermal growth factor fold, while the remaining
      peptides have features suggestive of a capacity to form amphipathic helices. We
      show that these peptides are derived from what appears to be a single,
      pharmacologically diverse, gene superfamily (aculeatoxins) that includes most
      venom peptides previously reported from the aculeate Hymenoptera. Two
      aculeatoxins purified from the venom were found to be capable of activating
      mammalian sensory neurons, consistent with the capacity to produce pain but via
      distinct mechanisms of action. Further investigation of the major venom peptide
      MIITX1-Mg1a revealed that it can also incapacitate arthropods, indicative of dual
      utility in both defense and predation. MIITX1-Mg1a accomplishes these functions
      by generating a leak in membrane ion conductance, which alters membrane potential
      and triggers neuronal depolarization. Our results provide the first insights into
      the evolution of the major toxin gene superfamily of the aculeate Hymenoptera and
      provide a new paradigm in the functional evolution of toxins from animal venoms.

PMID- 30214942
TI  - Experiences of type 2 diabetes in sub-Saharan Africa: a scoping review.
AB  - Background: The prevalence of diabetes in Sub-Saharan Africa (SSA) is growing
      rapidly. Qualitative research on experiences of type 2 diabetes in SSA is
      emerging, but no qualitative synthesis has been attempted. This scoping review
      aims to redress this lack of synthesis and to extract policy-relevant suggestions
      from the literature. Methods: Scoping review methodology was employed. Eleven
      online databases were searched (CINAHLplus, Cochrane Library, EBESCOhost, GALE
      Group, MEDLINE, Pro-Quest, Pscyhinfo, Pubmed, SCOPUS, Web of Science, WorldCat),
      using terms designed to identify qualitative studies of experiences of diabetes
      in SSA. Findings from records identified in the search were analysed inductively
      in NVivo 10 in three stages, to produce an analytical synthesis of studies of
      diabetes experiences in SSA. Results: Searches were conducted in 2017 and
      identified 2743 records, which were reduced to 21 after screening. The earliest
      identified record was published in 2003 and there was a clustering of records
      published between 2014 and 2016. The 21 records were based in eight SSA
      countries: Cameroon, Ethiopia, Ghana, Senegal, South Africa, Tanzania, Uganda,
      and Zimbabwe. A majority of the studies were conducted in Ghana (5) and South
      Africa (5), limiting the generalisability of our findings.The analytical
      synthesis produced five themes: identifying type 2 diabetes (how participants
      conceptualise and position their illnesses); hybridity of diabetes care (how
      multiple forms of care are often blended and/or pursued concurrently);
      impediments, improvisation and diabetes management (describing challenges faced,
      how these are responded to and management via diet and physical activity);
      sources of support (who supports participants and how); and diabetes and HIV/AIDs
      (the ways in which the two conditions are sometimes confused and how stigma is
      often experienced). Conclusions: The experiences of people with type 2 diabetes
      in SSA are under-researched across the region, pointing to a gap in knowledge.
      Interpreting our analytical synthesis, we suggest three priority areas for policy
      makers and implementers. Firstly, uncertainties relating to access to diabetes
      treatment need to be reduced. Secondly, more needs to be done to acknowledge and
      alleviate the economic struggles that those with diabetes face. Finally, high
      quality information and education would improve recognition and management of the
      condition.

PMID- 30214939
TI  - Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells
      that correlate with stage and survival.
AB  - High lethality rates associated with metastatic cancer highlight an urgent
      medical need for improved understanding of biologic mechanisms driving metastatic
      spread and identification of biomarkers predicting late-stage progression.
      Numerous neoplastic cell intrinsic and extrinsic mechanisms fuel tumor
      progression; however, mechanisms driving heterogeneity of neoplastic cells in
      solid tumors remain obscure. Increased mutational rates of neoplastic cells in
      stressed environments are implicated but cannot explain all aspects of tumor
      heterogeneity. We present evidence that fusion of neoplastic cells with
      leukocytes (for example, macrophages) contributes to tumor heterogeneity,
      resulting in cells exhibiting increased metastatic behavior. Fusion hybrids
      (cells harboring hematopoietic and epithelial properties) are readily detectible
      in cell culture and tumor-bearing mice. Further, hybrids enumerated in peripheral
      blood of human cancer patients correlate with disease stage and predict overall
      survival. This unique population of neoplastic cells provides a novel biomarker
      for tumor staging, as well as a potential therapeutic target for intervention.

PMID- 30214943
TI  - Validation of a Swahili version of the World Health Organization 5-item well
      being index among adults living with HIV and epilepsy in rural coastal Kenya.
AB  - Objective: The purpose of this study was to evaluate the psychometric properties
      of the World Health Organization's five item well-being index (WHO-5) when
      administered to adults living with HIV or epilepsy in a rural setting at the
      coast of Kenya. Methods: A case control study design was conducted among 230
      adults aged 18-50 years, who comprised 147 cases (63 living with epilepsy and 84
      living with HIV) and 83 healthy controls. The participants were administered to a
      face-to-face interview during which they completed the Swahili version of WHO-5
      well-being index, the Major Depression Inventory (MDI) and responded to some
      items on their socio-demographic characteristics. Analysis to assess internal
      consistency, construct validity, discriminant validity, and convergent validity
      of the Swahili version of WHO-5 well-being index was conducted. A multivariate
      regression was carried out to assess the association between psychological
      wellbeing (assessed using Swahili version of WHO-5 well-being index) and having a
      chronic illness (HIV or epilepsy). Results: The Swahili version of WHO-5 well
      being index demonstrated good internal consistency with Cronbach alpha ranges of
      0.86-0.88 among the three study groups. The tool had good discriminant validity.
      A one factor structure of the tool was obtained from confirmatory factor analysis
      (overall Comparative Fit Index = 1.00, Tuckler Lewis Index = 1.01, Root Mean
      Square of Error Approximation = 0.00). Living with HIV or epilepsy in comparison
      to being a healthy control was significantly associated with greater odds of
      having sub-optimal psychological wellbeing. Conclusion: Our findings demonstrate
      that the Swahili version of WHO-5 well-being index has good psychometric
      properties and is appropriate for use to evaluate psychological well-being among
      adults living with chronic conditions such as HIV or epilepsy from a rural low
      resource setting in Kenya. Given its brevity and ease of use, the Swahili version
      of WHO-5 well-being index could potentially be used by lay workers and other
      paraprofessional to monitor psychological well-being among chronically ill adults
      in resource poor settings.

PMID- 30214944
TI  - Individual-level modifiers of the acute effects of air pollution on mortality in
      Wuhan, China.
AB  - Background: Ambient air pollution has posed negative effects on human health.
      Individual-level factors may modify this effect, but previous studies have
      controversial conclusions, and evidence is lacking especially in developing
      countries. This study aims to examine the modifying effects of sex, age, and
      education level of individuals on the associated between daily mortality and air
      pollutants, including particulate matter < 10 MUm in aerodynamic diameter (PM10),
      sulfur dioxide (SO2), and nitrogen dioxide (NO2). Methods: Time-series analysis
      was conducted to investigate the acute effects of the air pollution on daily
      mortality from January 2002 to December 2010 in Wuhan, China. Generalized
      Additive Models (GAM) were used to examine the association stratified by sex for
      non-accidental, cardiovascular, and respiratory mortality. For non-accidental
      mortality, stratified analysis was also conducted by age and educational level.
      Results: Outdoor air pollution was associated with daily non-accidental and
      cardiovascular mortality. An increase of 10 MUg/m3 in a 2-day average
      concentration of PM10, SO2, and NO2 was corresponding to the increase in non
      accidental mortality of 0.29% (95%CI: 0.06-0.53%), 1.22% (95%CI: 0.77-1.67%) and
      1.60% (95%CI: 1.00-2.19%), respectively. The effects of air pollution were faster
      in females than males. The magnitude of the estimates was higher for females with
      low education, aged 65-75 years for PM10 and < 65 years for SO2. To be more
      specific, we observed that per 10 MUg/m3 increase in SO2 was association with
      increases in non-accidental mortality of 2.03% (95%CI: 1.38-2.67) for all females
      and 3.10% (95%CI: 2.05-4.16) for females with low education. Conclusion: Females
      and people with low-education are more susceptible to the effect of air
      pollution, which would provide a sound scientific basis for determination of air
      pollution standards.

PMID- 30214945
TI  - Postoperative pain management in patients undergoing posterior spinal fusion for
      adolescent idiopathic scoliosis: a narrative review.
AB  - Posterior spinal fusion for adolescent idiopathic scoliosis is one of the most
      invasive surgical procedures performed in children and adolescents. Because of
      the extensive surgical incision and massive tissue trauma, posterior spinal
      fusion causes severe postoperative pain. Intravenous patient-controlled analgesia
      with opioids has been the mainstay of postoperative pain management in these
      patients. However, the use of systemic opioids is sometimes limited by opioid
      related side effects, resulting in poor analgesia. To improve pain management
      while reducing opioid consumption and opioid-related complications, concurrent
      use of analgesics and analgesic modalities with different mechanisms of action
      seems to be rational. The efficacy of intrathecal opioids and nonsteroidal anti
      inflammatory drugs as components of multimodal analgesia in scoliosis surgery has
      been well established. However, there is either controversy or insufficient
      evidence regarding the use of other analgesic methods, such as continuous
      ketamine infusion, perioperative oral gabapentin, acetaminophen, continuous wound
      infiltration of local anesthetics, a single dose of systemic dexamethasone, and
      lidocaine infusion in this patient population. Moreover, appropriate combinations
      of analgesics have not been established. The aim of this literature review is to
      provide detailed information of each analgesic technique so that clinicians can
      make appropriate choices regarding pain management in patients with adolescent
      idiopathic scoliosis undergoing posterior spinal fusion.

PMID- 30214947
TI  - The effects of warm water immersion on blood pressure, heart rate and heart rate
      variability in people with chronic fatigue syndrome.
AB  - Background: Chronic fatigue syndrome (CFS) is a central sensitisation syndrome
      with abnormalities in autonomic regulation of blood pressure (BP), heart rate
      (HR) and heart rate variability (HRV). Prior to exploring the effects of
      hydrotherapy as a treatment for this population, changes in BP, HR and HRV during
      warm water immersion need to be established. Objectives: The study aimed to
      determine the effects of warm water immersion on BP, HR and HRV in adults with
      CFS compared to matched-pair healthy adults. Method: A quasi-experimental, single
      blinded study design was used with nine CFS participants and nine matched
      controls. Participants' BP, HR and HRV were measured before, after 5 minutes and
      post warm water immersion at the depth of the fourth intercostal space, using the
      Ithlete(r) System and Drager BP monitor. Results: There was a significant
      difference between groups in HRV prior to immersion (control group: 73 [55-74]
      vs. chronic fatigue syndrome group: 63 [50-70]; p = 0.04). There was no
      difference in HRV post-immersion. A significant difference in HR after immersion
      was recorded with the control group having a lower HR than those with CFS (78 [60
      86] vs. 86 [65-112]; p = 0.03). The low HRV present in the CFS group prior to
      immersion suggests autonomic dysregulation. Individuals with CFS may have reduced
      vagal nerve activation post-immersion. During immersion, HRV of the CFS
      participants improved similar to that of the healthy controls. Conclusion: Prior
      to immersion, differences were present in the HRV of the participants with CFS
      compared to healthy controls. These differences were no longer present post
      immersion. Clinical implications: Warm water immersion appears safe and may be
      beneficial in the management of individuals with CFS.

PMID- 30214948
TI  - Knowledge, attitude and practice of physiotherapists towards health promotion in
      Ghana.
AB  - Background: Physiotherapists are well equipped to address health promotion issues
      with their patients and the public. However, no studies have been conducted in
      Ghana to assess the knowledge, attitude and practice of physiotherapists towards
      health promotion. Objectives: This study therefore seeks to determine the
      knowledge, attitude and practice of physiotherapists towards health promotion in
      Ghana. Methods: This cross-sectional study was conducted at some selected
      physiotherapy departments in health facilities across Ghana. Ninety-one
      registered physiotherapists living and working in Ghana were recruited for this
      study. A closed-ended self-administered questionnaire was used to collect data on
      the demographics, knowledge, attitude and practice of physiotherapists towards
      health promotion. The scores for each section were calculated individually, and
      the final knowledge, attitude and practices score was obtained by calculating the
      total of the three sections. Statistical Package for Social Sciences version 22.0
      was employed to analyse all the study variables. Results: Physiotherapists'
      knowledge was 72%, attitude 84% and practice 87% towards health promotion. The
      association between the physiotherapists' knowledge of health promotion and
      practice was significant with Pearson's chi-square test (p = 0.013). But there
      was no significant association between knowledge and attitude of physiotherapists
      towards health promotion (p = 0.097). Conclusion: Physiotherapists have very good
      knowledge, attitude and practice towards health promotion in Ghana. This is
      essential for better integration into the scope of physiotherapy practice, and
      therefore, the health promotion policy in Ghana should be revised to include
      physiotherapists, because they are experts in exercise prescription and physical
      activity. Clinical implications: The outcomes of this study could provide the
      impetus for physiotherapists to include health promotion in clinical and
      community services for primary prevention of non-communicable diseases as well as
      secondary and tertiary prevention of disability to promote functional
      independence.

PMID- 30214946
TI  - Effects of shoulder strapping in patients with stroke: A randomised control
      trial.
AB  - Background: Disability post stroke remains a global problem, with upper limb
      involvement playing a key role. Shoulder strapping is one of the techniques used
      clinically to address this. Objectives: To compare the effect of two shoulder
      strapping techniques in patients with stroke. Method: A longitudinal randomised
      controlled trial included baseline, weeks one, two and six assessments of 56
      participants with upper limb hemiplegia. The participants were assessed for
      shoulder subluxation, shoulder pain, upper limb motor function and muscle tone.
      They were randomised into control, longitudinal strapping or circumferential
      strapping groups. Results: Longitudinal strapping had a non-significant decrease
      in shoulder subluxation and pain (p > 0.05). Circumferential strapping had no
      significant effect on any outcomes; however, it prevented the shoulder pain from
      worsening as much as in the control group (p > 0.05). General improvement in
      upper limb motor function was observed for all three groups. Conclusion: Trends
      in improvement showed that longitudinal strapping could be recommended because it
      positively influenced shoulder subluxation and pain. Even without significant
      changes, strapping creates awareness of the limb in patients and caregivers and
      could be of clinical benefit. Clinical implication: Longitudinal strapping of the
      shoulder in patients with stroke seems to positively influence shoulder
      subluxation and pain.

PMID- 30214949
TI  - Impact of the Chelsea critical care physical assessment (CPAx) tool on clinical
      outcomes of surgical and trauma patients in an intensive care unit: An
      experimental study.
AB  - Background: Critically ill patients following traumatic injury or major surgery
      are at risk of loss of skeletal muscle mass, which leads to decreased physical
      function. Early rehabilitation in an intensive care unit (ICU) is thought to
      preserve or restore physical functioning. The Chelsea critical care physical
      assessment (CPAx) is a measurement tool used to assess physical function in the
      ICU. Objectives: To determine whether the use of the CPAx tool as part of
      physiotherapy patient assessment, in two adult trauma and surgical ICU settings
      where early patient mobilisation forms part of standard physiotherapy practice,
      had an impact on ICU and hospital length of stay (LOS) through delivery of
      problem-oriented treatment plans. Method: A single-centred pre-post quasi
      experimental study was conducted. The population was a consecutive sample of
      surgical and trauma ICU patients. Participants' functional ability was assessed
      with the CPAx tool on alternative days during their ICU stay, and rehabilitation
      goals were modified according to their CPAx score. Intensive care unit and
      hospital LOS data were collected and compared to data of a matched historical
      control group. Descriptive and inferential statistics were used. Results: A total
      of 26 ICU patients were included in the intervention group (n = 26). They
      received CPAx-guided therapy, and outcomes were matched with ICU patients in the
      historical control group (n = 26). The median sequential organ failure assessment
      (SOFA) score was significantly higher in the control group (p = 0.005) (3.5 [IQR
      2-6.3]) versus (2 [IQR 1.8-2.5]) for the intervention group. The median admission
      CPAx score for the intervention group was 33.5 (IQR 16.1-44), and the median ICU
      discharge score was 38 (IQR 28.5-43.8). No significant differences were found in
      ICU days (control 2.7 [IQR 1.1-5.2]; intervention 3.7 [IQR 2.3-5.4]; p = 0.27) or
      hospital LOS (control 13.5 [IQR 9.3-18.3]; intervention 11.4 [IQR 8.4-20.3], p =
      0.42). Chelsea critical care physical assessment scores on ICU admission had a
      moderate negative correlation with hospital LOS (r = -0.58, p = 0.00, n = 23).
      Chelsea critical care physical assessment scores at ICU discharge had strong
      positive correlation with discharge SOFA scores (r = 0.7; p = 0.025; n = 10).
      Conclusion: Problem-oriented patient rehabilitation informed by the CPAx tool
      resulted in improvement of physical function but did not reduce ICU or hospital
      LOS. Clinical implications: A higher level of physical function at ICU admission,
      measured with CPAx, was associated with shorter hospital LOS.

PMID- 30214952
TI  - The practice of clinical neurophysiology.

PMID- 30214950
TI  - The efficacy of kinesiology taping for improving gross motor function in children
      with cerebral palsy: A systematic review.
AB  - Background: Kinesiology taping is an increasingly popular technique used as an
      adjunct to physiotherapy intervention for children with cerebral palsy (CP), but
      as yet we do not have a review of the available evidence as to its efficacy.
      Objectives: To critically appraise and establish best available evidence for the
      efficacy of truncal application of kinesiology taping combined with
      physiotherapy, versus physiotherapy alone, on gross motor function (GMF) in
      children with CP. Method: Seven databases were searched using the terms CP,
      kinesio taping and/or kinesiology tape and/or taping, physiotherapy and/or
      physical therapy and GMF. Only randomised controlled trials (RCTs) were included
      and appraised using the PEDro scale. Revman(c) Review Manager was used to combine
      effects for GMF in sitting, standing and activities of daily living. Results:
      Five level IIB RCTs that scored 3-6/8 on the PEDro scale were included. Meta
      analysis showed that taping was effective for improving GMF in sitting and
      standing as measured by the Gross Motor Function Measure (B) (p < 0.001) and (D)
      (p < 0.001), respectively. Conclusion: There is moderate evidence to support
      kinesiology taping applied to the trunk as an effective intervention when used as
      an adjunct to physiotherapy to improve GMF in children with CP, especially those
      with GMF Classification Scale levels I and II, and particularly for improving
      sitting control. Clinical implications: Kinesiology taping is a useful adjunct to
      physiotherapy intervention in higher functioning children with CP. Current
      evidence however is weak and further research into methods of truncal application
      is recommended.

PMID- 30214951
TI  - A verbal descriptor incremental pain scale developed by South African Tswana
      speaking patients with low back pain.
AB  - Background: Measuring pain in patients whose home language is not English can be
      difficult as there may not be a scale available in their home language. Scales
      devised in other countries may also not be accurate after translation.
      Objectives: The aim of this study was to develop and test a new verbal pain
      descriptor scale in a Tswana-speaking population in South Africa with low back
      pain. Method: Two separate Tswana-speaking groups (20 males and 20 females) of
      patients with low back pain were asked to describe each of four categories of
      pain: mild, moderate, severe and worst. They then voted and descriptions
      obtaining more than 70% of the vote were taken to the next round of voting with
      both groups together. A final scale of one description for each category of pain
      (Tswana Verbal Pain Descriptor Scale - TVPDS) for both males and females was
      tested on a sample of 250 patients with low back pain and against three other non
      verbal pain scales. Results: All items on the final scale were approved by at
      least 70% of both male and female participants. The scores for the TVPDS
      correlated well with present pain perception (r = 0.729, p < 0.0001) measured on
      the numerical visual analogue scale. The TVPDS correlated well with the Wong
      Baker FACES Pain Rating Scale (r = 0.695, p < 0.0001) and the Pakistani Coin Pain
      Scale (r = 0.717, p < 0.0001). Conclusion: The TVPDS has the potential to be a
      useful clinical scale but more testing in other languages is still required.
      Clinical implications: This pain scale has the potential to be a useful scale to
      use for Tswana-speaking persons with low back pain and could also be useful for
      persons of other languages, if translated.

PMID- 30214953
TI  - The utility of electrodiagnostic tests for the assessment of medically
      unexplained weakness and sensory deficit.
AB  - Patients with suspected medically unexplained symptoms or psychogenic disorders
      are frequently requested to undergo an EMG exam. However, the suspected diagnosis
      is not always told to the electromyography practitioner, who must be able to
      recognize such a condition to avoid false positive diagnosis without dismissing
      the possibility to uncover any true dysfunction. There are many clinical
      manoeuvers to assess the consistency of the patients' reported weakness or
      sensory deficit. The electrodiagnostic practitioner should be aware of those
      clinical tricks and interpret the electrodiagnostic findings in the clinical
      context. There are many electrodiagnostic tests that the practitioner can use for
      the assessment of motor and sensory functions but these tests have also important
      drawbacks and limitations. Only after a good clinical evaluation would the
      practitioner be able to give his/her opinion on the clinical relevance of the
      electrodiagnostic findings. Here we review some of the tests that can help the
      practitioner to define the electrophysiological characteristics of a suspected
      functional disorder presenting with weakness or sensory deficit.

PMID- 30214954
TI  - Clinical uses of H reflexes of upper and lower limb muscles.
AB  - H reflexes can be recorded from virtually all muscles that have muscle spindles,
      but reflex reinforcement may be required for the reflex response to be
      demonstrable. This can allow conduction across proximal nerve segments and most
      nerve root segments commonly involved by pathology. Stimulus rate is critical in
      subjects who are at rest. However the reflex attenuation with higher rates is
      greatly reduced during a background contraction of the test muscle, with only
      minor changes in latency if any. In addition the contraction ensures that the
      reflex response occurs in the desired muscle. Reflex latencies should be
      corrected for height (or limb length) and age. Because the reflex discharge
      requires a synchronised volley in group Ia afferents, large increases in reflex
      latency occur rarely with purely sensory lesions. If the H reflex of soleus,
      quadriceps femoris or flexor carpi radialis is absent at rest but appears during
      a voluntary contraction at near-normal latency, there is either low central
      excitability or a predominantly sensory abnormality. With the former H reflexes
      will be difficult to elicit throughout the body. If H reflexes can be recorded at
      rest from muscles for which no reflex can normally be demonstrated, there is good
      evidence for hyperreflexia. In the context of possible ALS, this is an important
      finding when there is EMG evidence of chronic partial denervation in that muscle.

PMID- 30214955
TI  - Antidromic vs orthodromic sensory median nerve conduction studies.
AB  - Objective: Median sensory nerve conduction studies are arguably the most often
      performed electrodiagnostic tests worldwide. Routine tests in clinical practice
      are done using either antidromic or orthodromic techniques type of stimulation,
      with no universal agreement on the use of one or the other technique. Methods: We
      review the advantages and drawbacks of antidromic and orthodromic as well as
      their particularities for clinical application and research. Results: The two
      techniques differ on how physical and physiological changes affect the action
      potential. Near-nerve recording is better suited for the orthodromic than for the
      antidromic technique, while studies of nerve excitability are better suited for
      the antidromic than for the orthodromic technique. Conclusion: Both techniques
      are equally suitable for routine tests but research studies may specifically
      demand one or the other.

PMID- 30214956
TI  - Psychophysical estimate of plantar vibration sensitivity brings additional
      information to the detection threshold in young and elderly subjects.
AB  - Objective: Vibration detection threshold of the foot sole was compared to the
      psychophysical estimate of vibration in a wide range of amplitudes in young (20
      34 years old) and elderly subjects (53-67 years old). Methods: The vibration
      detection threshold was determined on the hallux, 5th metatarsal head, and heel
      at frequencies of 25, 50 and 150 Hz. For vibrations of higher amplitude (reaching
      360 MUm), the Stevens power function (Psi = k * Phin ) allowed to obtain
      regression equations between the vibration estimate (Psi) and its physical
      magnitude (Phi), the n coefficient giving the subjective intensity in vibration
      perception. We searched for age-related changes in the vibration perception by
      the foot sole. Results: In all participants, higher n values were measured at
      vibration frequencies of 150 Hz and, compared to the young adults the elderly had
      lower n values measured at this frequency. Only in the young participants, the
      vibration detection threshold was lowered at 150 Hz. Conclusion: The
      psychophysical estimate brings further information than the vibration detection
      threshold which is less affected by age. Significance: The clinical interest of
      psychophysical vibration estimate was assessed in a patient with a unilateral
      alteration of foot sensitivity.

PMID- 30214957
TI  - Home Video Telemetry vs inpatient telemetry: A comparative study looking at video
      quality.
AB  - Objective: To compare the quality of home video recording with inpatient
      telemetry (IPT) to evaluate our current Home Video Telemetry (HVT) practice.
      Method: To assess our HVT practice, a retrospective comparison of the video
      quality against IPT was conducted with the latter as the gold standard. A pilot
      study had been conducted in 2008 on 5 patients.Patients (n = 28) were included in
      each group over a period of one year.The data was collected from referral
      spreadsheets, King's EPR and telemetry archive.Scoring of the events captured was
      by consensus using two scorers.The variables compared included: visibility of the
      body part of interest, visibility of eyes, time of event, illumination, contrast,
      sound quality and picture clarity when amplified to 200%.Statistical evaluation
      was carried out using Shapiro-Wilk and Chi-square tests. The P-value of ?0.05 was
      considered statistically significant. Results: Significant differences were
      demonstrated in lighting and contrast between the two groups (HVT performed
      better in both).Amplified picture quality was slightly better in the HVT group.
      Conclusion: Video quality of HVT is comparable to IPT, even surpassing IPT in
      certain aspects such as the level of illumination and contrast. Results were
      reconfirmed in a larger sample of patients with more variables. Significance:
      Despite the user and environmental variability in HVT, it looks promising and can
      be seriously considered as a preferable alternative for patients who may require
      investigation at locations remote from an EEG laboratory.

PMID- 30214958
TI  - Tongue myokymia presenting twelve years after radiation therapy.
AB  - Objective: This case is a patient with tongue myokymia following radiation
      therapy 12 years earlier, documented using video and EMG. Case report: A 68-year
      old woman with a history of nasopharyngeal carcinoma presented with subacute
      onset of difficulty in speaking and involuntary movements of her tongue
      approximately 12 years after radiation therapy to head and neck. Electromyography
      displayed myokymic discharges. There was no evidence of recurrent malignancy.
      Significance: Delayed effects of radiation therapy might be seen decades later.
      Myokymic discharges may reveal radiation-induced neuropathy.

PMID- 30214959
TI  - Electrochemical skin conductance for quantitative assessment of sweat function:
      Normative values in children.
AB  - Objectives: The SudoscanTM system (Impeto Medical, Paris, France) has been
      recently proposed as a standardized, easy, painless tool for sudomotor function
      assessment. It is now used as an additional diagnostic tool in small fibre
      neuropathy. So far, no work has been published in children. The aim of this study
      was to measure electrochemical skin conductance (ESC) using the SudoscanTM system
      in children in order to assess its feasibility and to provide normative values.
      Methods: 100 children were included in the study: 55 girls and 45 boys, age rank
      2-17, mean 10.5 y. They were accompanying their brother or sister who came as
      outclinic patients in the Department of Paediatrics or the Department of
      Paediatric surgery of the University Hospital. Results: All subjects underwent
      the test. It was performed without any difficulty, except for some of the
      youngest who sometimes had some trouble in keeping calm for 3 min over the
      plates. 4 subjects who took the test were excluded from the analysis (2 diabetic
      patients and 2 having had previous chemotherapy). ESC was quite stable along
      childhood with an overall 80.1 MUS value for hands and 81.9 MUS for feet, very
      similar to what is observed in adults. Conclusion: Maturation process seems to
      occur early in life, in accordance to sudomotor control when assessed by
      sympathetic skin response, which is also recorded early in infancy. Significance:
      ESC measurement is a simple and easy-to-perform test that can be performed in the
      clinical setting in children in 5 min.

PMID- 30214960
TI  - Suprasegmental neurophysiological monitoring with H reflex and TcMEP in spinal
      surgery. Transient loss due to hypotension. A case report.
AB  - Objective: H-reflex is a well known neurophysiological test used to evaluate
      sensory afferent and motor efferent impulses of S1 root. Despite its simplicity
      and feasibility, it is not used very often in the operating room. Methods: We
      report the case of a 16-year-old male patient who undergoes a surgical correction
      for a severe paralytic scoliosis (160 degrees ). On account of previous deficits,
      intraoperative neurophysiological monitoring was achieved through TcMEP and H
      reflex. Results: Intraoperative neurophysiological monitoring (IONM) showed a
      transient and simultaneous loss of bilateral TcMEP and H-reflex, coinciding with
      an abrupt hypotension during pedicle screw placement. After having dismissed
      mechanical injury and after increasing blood pressure, TcMEP and H-reflex were
      equivalent to those at baseline. Conclusions: The H-reflex is a classic
      neurophysiological test not used very frequently in the operating room. It is a
      feasible and reliable technique that can be helpful during spine surgery IONM,
      especially in patients with preexisting neurological deficits. Although
      simultaneous TcMEP and H-reflex monitoring has been previously described, to our
      knowledge, this is the first recorded case of a decline in both associated with
      abrupt hypotension.

PMID- 30214961
TI  - Potential risks of iatrogenic complications of nerve conduction studies (NCS) and
      electromyography (EMG).
AB  - Nerve conduction and electromyography studies are generally well tolerated and
      pose little risk to patients of serious adverse events in the hands of a well
      trained competent practitioner. However, some patients and certain examinations
      do carry a higher risk of potential complications. It is good medical practice to
      inform patients of any risks, their potential severity and relative frequency. In
      order to obtain informed consent a dialogue should take place about the nature,
      purpose and effects of the studies, so patients can decide if they wish to
      undergo the proposed investigation. In this educational review we identify those
      procedures and patients at risk, and provide pragmatic practice recommendations
      for managing these material risks.

PMID- 30214962
TI  - Operator differences in thermal quantitative sensory testing.

PMID- 30214963
TI  - Unilateral suppression of P/N13' potential amplitude in young patients with
      persistent numbness due to cervical monoradiculopathy. A case-control study.
AB  - Objective: The utility of Dermatomal Somatosensory Evoked Potentials (DSEPs) in
      the diagnostic workup of suspected cervical monoradiculopathy has been limited by
      significant overlap between measurements obtained from affected versus unaffected
      roots. In a case-control study, we explored whether, under certain conditions,
      asymmetry in DSEP parameters may offer significant help in the diagnosis of
      monoradiculopathy. Methods: DSEPs were obtained bilaterally from patients with
      persistent (age range 33-55, n = 10) or intermittent (age range 31-55, n = 7)
      unilateral sensory symptoms of less than one month duration due to MRI-confirmed
      cervical monoradiculopathy. DSEPs were also obtained bilaterally from aged
      matched asymptomatic volunteers (age range 31-54, n = 8) and older asymptomatic
      volunteers (age range 57-77, n = 8). Amplitude and latency of the P/N13'
      potential (negative peak at 13 ms) were measured. Results: In all ten patients
      with persistent symptoms, the P/N13' amplitude ratio, defined as P/N13' amplitude
      on the symptomatic side divided by P/N13' amplitude on the contralateral
      asymptomatic side, ranged between 0.0 and 0.50 (unilateral suppression). In all
      seven patients with intermittent symptoms, P/N13' amplitude ratios ranged between
      0.60 and 1.00. In all age-matched asymptomatic controls, P/N13' amplitude ratio
      (side with lower divided by side with higher amplitude) was always at least 0.80.
      Among older asymptomatic subjects, DSEPs had inconsistent characteristics.
      Conclusions: Cervical monoradiculopathy with persistent numbness in young
      patients (aged up to 55 years) is very strongly associated with unilateral
      suppression of P/N13' DSEP amplitude. No significant asymmetry is observed in
      cases of monoradiculopathy with intermittent numbness. Significance: In young
      patients with unilateral upper extremity persistent sensory complaints, DSEP
      amplitude asymmetry, as quantified by the P/N13' ratio, may offer significant
      help in the diagnosis of monoradiculopathy.

PMID- 30214964
TI  - Electrophysiological evidence of the Riche-Cannieu anastomosis in the hand and
      its diagnostic implications; 2 case reports.
AB  - Introduction: Anomalous anastomoses between the nerves of the hand are not as
      rare as thought to be. Amongst these, the Riche-Cannieu anastomosis (RCA) is a
      connection between the ulnar nerve and median motor nerve in the palm. Presence
      of this can sometimes be misdiagnosed as a severe median mononeuropathy at the
      wrist/carpal tunnel syndrome (CTS).We describe two cases that were referred for
      evaluation of CTS and were found to have incidental RCA. Results:
      Electrophysiological studies showed typical findings consistent with RCA and
      coexistent mild CTS. Patients in whom median sensory and motor latency
      prolongations suggest CTS, the presence of an anastomosis should be suspected if
      the median motor amplitudes are worse than the median sensory amplitudes.
      Conclusion: The electrophysiological study should be extended to avoid erroneous
      interpretation of low median motor amplitudes as severe CTS and to prevent
      unnecessary surgical intervention.

PMID- 30214965
TI  - Characteristics and clinical significance of delta brushes in the EEG of
      premature infants.
AB  - Delta brushes are the hallmark of the EEG of premature infants. They are readily
      recognisable because of their characteristic appearance and are a key marker of
      neural maturation. However they are sometimes inconsistently described in the
      literature making identification of abnormalities challenging. The goal of this
      review is to provide an overview of research findings on this topic in the last
      five decades. Firstly, the characteristic features of delta brushes are
      described, including the developmental trajectory of their incidence and how they
      are modulated by vigilance state in normal neonates. Secondly, their clinical
      significance is discussed including how abnormalities in their incidence or
      appearance indicate particular pathophysiology. We propose that (i) the effect of
      age and vigilance state on the frequency, amplitude and topography of delta
      brushes, and (ii) heterogeneity within the cohorts of 'normal' premature infants
      studied, may explain the very variable descriptions of delta brush
      characteristics in the literature. By explicitly taking these factors into
      consideration to explain delta brush variability, the presented summary
      facilitates the clinical electrodiagnostic and prognostic use of delta brush
      abnormalities as a biomarker.

PMID- 30214967
TI  - Repeatability of long intracortical inhibition in healthy subjects.
AB  - Objectives: Transcranial magnetic stimulation (TMS) is widely used to assess
      cortical excitability. To detect changes in excitability with longitudinal
      studies, it is important to validate the repeatability of excitability measures
      within a subject between different sessions. Repeatability studies on long
      intracortical inhibition (LICI) are limited and reported agreement ranges from
      poor to good. This study aims to evaluate the repeatability of LICI in healthy
      subjects using paired pulse TMS. In addition, it investigates whether LICI
      repeatability differs for manual and robot-guided coil positioning. Methods:
      Thirty healthy subjects (10 males, mean age 28.4 +/- 8.2 years) were studied
      twice, approximately one week apart. Both motor cortices were stimulated with 50
      paired pulses (intensity 120% of resting motor threshold) at interstimulus
      intervals (ISIs): 50, 100, 150, 200, 250 and 300 ms. In twenty subjects a figure
      of-eight coil was positioned and held in place manually during both sessions,
      while in ten subjects a robot-navigated arm was used. LICI repeatability was
      assessed using the intraclass correlation coefficient (ICC). Results: For manual
      and robot-guided coil positioning we found a large variation in repeatability at
      the subject level and ISI level, ranging from poor to good agreement. On a group
      level, we found good repeatability for averaged LICI curves (manual: ICC = 0.91,
      robot-guided: ICC = 0.95), which decreased when individual curves were correlated
      between sessions (manual: ICC = 0.76, robot-guided: ICC = 0.84). Conclusion: For
      a correct interpretation of longitudinal study outcomes it is important to know
      the subject specific LICI repeatability and to analyze each ISI individually.
      Furthermore, the added value of robot-guided coil positioning for paired pulse
      TMS seems limited. Significance: The large variation in LICI repeatability at the
      subject level and ISI level should be taken into account in longitudinal studies,
      while robot-guided coil positioning seems unnecessary.

PMID- 30214966
TI  - Adverse events of tDCS and tACS: A review.
AB  - Transcranial direct current stimulation (tDCS) and transcranial alternating
      current stimulation (tACS) have been applied to many research issues because
      these stimulation techniques can modulate neural activity in the human brain
      painlessly and non-invasively with weak electrical currents. However, there are
      no formal safety guidelines for the selection of stimulus parameters in either
      tDCS or tACS. As a means of gathering the information that is needed to produce
      safety guidelines, in this article, we summarize the adverse events of tDCS and
      tACS. In both stimulation techniques, most adverse effects are mild and disappear
      soon after stimulation. Nevertheless, several papers have reported that, in tDCS,
      some adverse events persist even after stimulation. The persistent events consist
      of skin lesions similar to burns, which can arise even in healthy subjects, and
      mania or hypomania in patients with depression. Recently, one paper reported a
      pediatric patient presenting with seizure after tDCS, although the causal
      relationship between stimulation and seizure is not clear. As this seizure is the
      only serious adverse events yet reported in connection with tDCS, tDCS is
      considered safe. In tACS, meanwhile, no persistent adverse events have been
      reported, but considerably fewer reports are available on the safety of tACS than
      on the safety of tDCS. Therefore, to establish the safety of tDCS and tACS, we
      need to scan the literature continuously for information on the adverse events of
      both stimulation techniques. Further safety investigations are also required.

PMID- 30214968
TI  - Normative values of semitendinosus tendon reflex latencies.
AB  - Objectives: The semitendinosus tendon reflex (STR), also known as the medial
      hamstring reflex, is rarely described in literature and is believed to provide
      information mainly concerning the fifth lumbar spinal nerve (L5). Latencies can
      be obtained with clinical neurophysiological tests. Normative data for STR
      latencies are not available. The aim of this study was to provide normative
      values of STR latencies. Also we will describe the technique used for performing
      the tendon reflex measurements in a clinical neurophysiological setting. Methods:
      To determine STR latencies, we measured the stimulus (tap with reflex hammer) -
      response (EMG activity associated with muscle contraction) relation. The stimulus
      was administered with a manually operated reflex hammer, tipped with electrically
      conductive rubber, triggering the EMG recording sweep on impact. The EMG response
      was recorded with surface electrodes placed on the skin overlying the
      semitendinosus muscle. Results: Forty healthy subjects participated in the study.
      The group consisted of 18 women and 22 men with a median age of 30 years. The
      mean subject body height was 181 cm (SD 8.1). Latencies showed a significant
      correlation with body height (r = 0.70, R2 = 0.48, P < 0.0001). The mean latency
      of the STR was 24.73 ms (SD 1.96). The rounded upper limit of normal of
      individual absolute right-left differences was 2 ms. Conclusion: We present, as
      far as we know, the first report on normative values of STR latencies. The STR
      could be elicited in 100% of our population. The left-right difference seems to
      be the most promising clinical parameter for diagnostic purposes. Significance:
      We think our results can be of practical use for all clinical
      neurophysiologists/neurologists and may provide the basis for further research on
      test characteristics of STR latencies in patients with L5 radiculopathy.

PMID- 30214969
TI  - Effects of active and passive warming of the foot sole on vibration perception
      thresholds.
AB  - Objective: Skin temperatures are known to increase cutaneous sensitivity.
      However, it is unclear whether the amount of improved sensitivity differs
      depending on the protocol of heat application. Therefore, this study aimed to
      investigate the effects of active (treadmill walking) and passive (infrared
      radiator) warming of the foot sole on vibration perception thresholds. Methods:
      Sixty healthy and injury-free subjects voluntarily participated in this study.
      Vibration perception thresholds (200 Hz) and plantar temperatures were measured
      at the hallux and 1st metatarsal head. In experiment 1, warming and mechanically
      stimulating the skin was achieved by walking on a treadmill for 30 min. In a
      follow-up study (experiment 2), external plantar heat was administered via an
      infrared radiator (30 min). Results: In both experiments, increasing temperatures
      led to increased plantar sensitivity. However, the amount of improved sensitivity
      was greater in experiment 1, although plantar temperature increases were lower
      compared to experiment 2. Conclusions: Warming in conjunction with mechanical
      stimulation seems to have a greater potential to enhance plantar sensitivity
      compared to external heat supply only. Significance: The possible influence of
      mechanical stimulation and warming towards superior plantar afferent feedback
      highlights its importance regarding human posture and fall prevention.

PMID- 30214970
TI  - Multi-channel motor evoked potential monitoring during anterior cervical
      discectomy and fusion.
AB  - Objectives: Anterior cervical discectomy and fusion (ACDF) surgery is the most
      common surgical procedure for the cervical spine with low complication rate.
      Despite the potential prognostic benefit, intraoperative neurophysiological
      monitoring (IONM), a method for detecting impending neurological compromise, is
      not routinely used in ACDF surgery. The present study aimed to identify the
      potential benefits of monitoring multi-channel motor evoked potentials (MEPs)
      during ACDF surgery. Methods: We retrospectively reviewed 200 consecutive
      patients who received IONM with multi-channel MEPs and somatosensory evoked
      potentials (SSEPs). On average, 9.2 muscles per patient were evaluated under MEP
      monitoring. Results: The rate of MEP change during surgery in the multi-level
      ACDF group was significantly higher than the single-level group. Two patients
      from the single-level ACDF group (1.7%) and four patients from the multi-level
      ACDF group (4.9%) experienced post-operative motor deficits. Multi-channel MEPs
      monitoring during single and multi-level ACDF surgery demonstrated higher
      sensitivity, specificity, positive predictive and negative predictive value than
      SSEP monitoring. Conclusions: Multi-channel MEP monitoring might be beneficial
      for the detection of segmental injury as well as long tract injury during single-
      and multi-level ACDF surgery. Significance: This is first large scale study to
      identify the usefulness of multi-channel MEPs in monitoring ACDF surgery.

PMID- 30214972
TI  - A case of bulbospinal muscular atrophy with large fasciculation manifesting as
      spinal myoclonus.
AB  - Objective: This paper reports a patient with bulbospinal muscular atrophy (BSMA)
      who presented with spinal myoclonus, documented by video and surface
      electromyography. Case report: A 66-year-old man had progressive gait
      disturbance, dysphagia, and easy fatigability of all extremities over a period of
      4 years. Neurologically, muscle atrophy, fasciculation, and weakness were
      observed in the bulbar and limb muscles. When the knees were kept in mild flexion
      in the supine position, fasciculation of the thigh adductor muscles was so large
      that it caused shock-like involuntary movements of the legs, corresponding to
      spinal myoclonus. A genetic test revealed 41 repeats of CAG in the androgen
      receptor gene, and the diagnosis of BSMA was made. Significance: The present case
      suggests that extremely large fasciculation can cause spinal myoclonus.

PMID- 30214971
TI  - Cortical dynamics during simple calculation processes: A magnetoencephalography
      study.
AB  - Objective: We elucidated active cortical areas and their time courses during
      simple calculation by using whole-scalp magnetoencephalography. Methods: Twelve
      healthy volunteers were asked to view meaningless figures (figure viewing) or
      digits (digit viewing) and add single digits (calculation). The magnetic signals
      of the brain were measured using a helmet-shaped 122-channel neuromagnetometer
      during the three tasks. Results: The occipital, inferior posterior temporal, and
      middle temporal areas of each hemisphere and the left superior temporal area
      (STA) were activated during all tasks (approximately 250 ms after the stimulus
      onset). The calculation-related sources were located in the left inferior
      parietal area (IPA) in 8 subjects, right IPA in 5, left STA in 3, right STA in 5,
      right inferior frontal area in 2, and left inferior frontal area in 1. The IPA
      and STA of the left hemisphere were activated more strongly and significantly
      earlier than those of the right hemisphere: the left IPA was activated first
      (mean activation timing: 301 ms), followed by activations of the left STA (369
      ms), right IPA (419 ms), and right STA (483 ms). Conclusions: Simple digit
      addition is executed mainly in the left IPA and left STA, followed by the
      recognition processes of results in the right IPA and right STA. Significance:
      This study clarified the cortical process during simple calculation, with
      excellent temporal and spatial resolution; the IPA and STA of the left hemisphere
      were activated more strongly and earlier than the corresponding areas of the
      right hemisphere.

PMID- 30214973
TI  - A rare type of fibrillation-like EMG activity.

PMID- 30214975
TI  - Afterdischarges following M waves in patients with voltage-gated potassium
      channels antibodies.
AB  - Objective: To explore the correlation between afterdischarges in motor nerve
      conduction studies and clinical motor hyperexcitability in patients with voltage
      gated potassium channels (VGKC) antibodies. Methods: Six patients with positive
      serum antibodies to contactin-associated protein-like 2 (CASPR2) or/and leucine
      rich glioma-inactivated protein 1 (LGI1) were recruited, including 5 with
      autoimmune encephalitis, and 1 with cramp-fasciculation syndrome.
      Electromyography (EMG), nerve conduction studies (NCS) and F waves were
      performed, and afterdischarges were assessed. One patient was followed up.
      Results: Five patients had clinical evidence of peripheral motor nerve
      hyperexcitability (myokymia or cramp), and four of them had abnormal spontaneous
      firing in concentric needle electromyography (EMG). Prolonged afterdischarges
      following normal M waves were present in all six patients, including the two
      patients who had no EMG evidence of peripheral nerve hyperexcitability (PNH).
      Afterdischarges disappeared after treatment with intravenous immunoglobulin
      (IVIG). Conclusion: The afterdischarges in motor nerve conduction study might be
      a sensitive indicator of peripheral motor nerve hyperexcitability in patients
      with VGKC antibodies. Significance: Afterdischarges in motor nerve conduction
      study might be more sensitive than needle electromyography for detecting
      peripheral motor nerve hyperexcitability, and could disappear gradually in
      accordance with clinical improvement and reduction of antibodies.

PMID- 30214974
TI  - Visual evoked potentials after hematopoietic allogeneic stem cell transplantation
      in childhood.
AB  - Objective: To study visual pathway pathology detected by visual evoked potentials
      (VEPs) in patients treated with hematopoietic stem cell transplantation (HSCT) in
      childhood and to determine the impact of adverse ocular findings, somatic
      diseases, and conditioning regimens on the VEP results. Methods: Ophthalmological
      assessments including pattern VEPs were performed in 47 of 79 patients at a
      median age of 15 years (range 3-21 years) in median 6 years (1-17 years) after
      HSCT. Somatic data were extracted from medical records. Results: Eight patients
      of 47 (17%) demonstrated pathological VEPs with prolonged latencies bilaterally
      (n = 3) or unilaterally (n = 5) at their latest VEP test at an age of 12-18
      years. A subnormal visual acuity was present in 8/11 eyes with pathological VEPs:
      one eye had cataract, six eyes had cataract surgery where of two had developed
      secondary cataracts. One eye had residual retinopathy of prematurity.
      Pathological VEPs were associated with decreased visual acuity (p = 0.00019) but
      not linked to gender, malignant diagnosis or conditioning. Conclusion: VEP
      recordings showed an association with decreased visual acuity but no relationship
      with irradiation or chemotherapy in the present study. Significance: VEP
      recordings might be of clinical value for children with an unexplained subnormal
      visual acuity undergoing HSCT.

PMID- 30214976
TI  - Clinical neurophysiology for neurological prognostication of comatose patients
      after cardiac arrest.
AB  - Early prognostication of outcome in comatose patients after cardiac arrest
      represents a daunting task for clinicians, also considering the nowadays commonly
      used targeted temperature management with sedation in the first 24-48 h. A
      multimodal approach is currently recommended, in order to minimize the risks of
      false-positive prediction of poor outcome, including clinical examination off
      sedation, EEG (background characterization and reactivity, occurrence of
      repetitive epileptiform features), and early-latency SSEP responses represent the
      core assessments in this setting; they may be complemented by biochemical markers
      and neuroimaging. This paper, which relies on a recent comprehensive review,
      focuses on an updated review of EEG and SSEP, and also offers some outlook into
      long-latency evoked potentials, which seem promising in clinical use.

PMID- 30214977
TI  - Use of eye tracking improves the detection of evoked responses to complex visual
      stimuli during EEG in infants.
AB  - Objective: To improve the reliability of detecting EEG responses evoked by
      complex visual stimuli to the level required for clinical use by integrating an
      eye tracker to the EEG setup and optimizing the analysis protocol. Methods:
      Infants were presented with continuous orientation reversal (OR), global form
      (GF), and global motion (GM) stimuli. Eye tracking was used to control stimulus
      presentation and exclude epochs with disoriented gaze. The spectral responses
      were estimated from 13 postcentral EEG channels using a circular variant of
      Hotelling's T2 test statistic. Results: Among 39 healthy infants, statistically
      significant (p < 0.01) responses to OR/GF/GM stimuli were found from 92%/100%/95%
      recordings, respectively. The specificity test of the detection algorithm, using
      non-stimulated baseline EEG, did not yield any false-positive findings. Taken
      together, this yields 15% improvement on average in the detection performance
      compared to that in the current literature. Conclusions: Changes to the test
      protocol and incorporation of the eye tracking information improves the detection
      of responses to complex visual stimuli in infants. Significance: This work
      presents a test protocol suitable for use in a clinical environment at a level of
      reliability that allows individual diagnostics.

PMID- 30214978
TI  - Comparison between adaptive and fixed stimulus paired-pulse transcranial magnetic
      stimulation (ppTMS) in normal subjects.
AB  - Objectives: Paired-pulse TMS (ppTMS) examines cortical excitability but may
      require lengthy test procedures and fine tuning of stimulus parameters due to the
      inherent variability of the elicited motor evoked potentials (MEPs) and their
      tendency to exhibit a 'ceiling/floor effects' in inhibition trials. Aiming to
      overcome some of these limitations, we implemented an 'adaptive' ppTMS protocol
      and compared the obtained excitability indices with those from 'conventional'
      fixed-stimulus ppTMS. Methods: Short- and long interval intracortical inhibition
      (SICI and LICI) as well as intracortical facilitation (ICF) were examined in 20
      healthy subjects by adaptive ppTMS and fixed-stimulus ppTMS. The test stimulus
      intensity was either adapted to produce 500 MUV MEPs (by a maximum likelihood
      strategy in combination with parameter estimation by sequential testing) or fixed
      to 120% of resting motor threshold (rMT). The conditioning stimulus was 80% rMT
      for SICI and ICF and 120% MT for LICI in both tests. Results: There were
      significant (p < 0.05) intraindividual correlations between the two methods for
      all excitability measures. There was a clustering of SICI and LICI indices near
      maximal inhibition ('ceiling effect') in fixed-stimulus ppTMS which was not
      observed for adaptive SICI and LICI. Conclusions: Adaptive ppTMS excitability
      data correlates to those acquired from fixed-stimulus ppTMS. Significance:
      Adaptive ppTMS is easy to implement and may serve as a more sensitive method to
      detect changes in cortical inhibition than fixed stimulus ppTMS. Whether equally
      confident data are produced by less stimuli with our adaptive approach (as
      already confirmed for motor threshold estimation) remains to be explored.

PMID- 30214979
TI  - Post-hypoxic myoclonus: Differentiating benign and malignant etiologies in
      diagnosis and prognosis.
AB  - Neurological function following cardiac arrest often determines prognosis.
      Objective tests, including formal neurological examination and neurophysiological
      testing, are performed to provide medical providers and decision-makers
      information to help guide care based on the extent of neurologic injury. The
      demonstration of post-hypoxic myoclonus on examination has been described to
      portend poor outcome after cardiac arrest, but recent studies have challenged
      this idea given that different forms of post-hypoxic myoclonus predict disparate
      prognoses. The presence of myoclonus status epilepticus (MSE) usually signals a
      poor outcome, especially if generalized. Lance-Adams syndrome (LAS), another form
      of post-hypoxic myoclonus, carries a better prognosis. Differentiating subtypes
      of post-hypoxic myoclonus is therefore critical. This can be difficult in the
      acute setting with clinical examination alone due to the use of sedation to
      facilitate mechanical ventilation, and neurophysiological studies may be more
      reliable. In this review, we describe and compare clinical and neurophysiological
      features of MSE and LAS. Generalized epileptiform activity and burst suppression
      on electroencephalography tend to be more common in MSE, and focal epileptiform
      activity at the vertex may define LAS. Those with multifocal MSE may have better
      outcomes than those with generalized MSE. We conclude that neurophysiological
      testing is vital acutely after cardiac arrest when post-hypoxic myoclonus is
      present to help determine prognostication and guide decision-making.

PMID- 30214981
TI  - Post-hypoxic myoclonus: The good, the bad and the ugly.

PMID- 30214980
TI  - Amyotrophic lateral sclerosis with a sudden-onset history.
AB  - Objective: We report on two patients with amyotrophic lateral sclerosis (ALS)
      complaining of sudden-onset difficulty in finger elevation. Case report: A 65
      year-old man (the first patient) and a 66-year-old man (the second patient)
      suddenly became aware of difficulty in finger elevation of one hand. They were
      not aware of any other symptoms prior to the onset. In the first patient,
      cerebral infarction at the precentral gyrus was initially suspected. In the
      second patient, cervical spondylosis was initially suspected, and cervical spine
      surgery was planned. However, needle EMG revealed widespread neurogenic changes
      and abundant fasciculation potentials for both patients. Widespread weakness
      emerged in time and relentlessly progressed, and finally the diagnosis of ALS was
      made. In both cases, notable weakness in the extensor digitorum (ED) muscle with
      relatively mild weakness in the other muscles in the affected limb was a
      characteristic finding. Loss of one motor unit in ED that has already enlarged
      due to reinnervation must have caused sudden awareness of the weakness.
      Significance: Clinicians should recognize the presence of ALS patients with a
      sudden-onset history because the risk of initial misdiagnosis is high for such
      patients.

PMID- 30214982
TI  - Population of the ictal-interictal zone: The significance of periodic and
      rhythmic activity.
AB  - Seizures contribute to patient mortality and are usually treated aggressively.
      Rhythmic and periodic patterns - the "ictal-interictal continuum" - are often
      associated with seizures, yet the optimum method of treating these patterns is
      not known: should they be aggressively suppressed, or monitored without
      treatment? Understanding which patterns are more strongly associated with
      seizures and which are highly associated with mortality is important to help the
      clinician decide how to treat these findings. We present an overview of the
      etiologies, association with seizures, and mortality of periodic and rhythmic
      patterns, and one approach to treatment.

PMID- 30214983
TI  - The temporal stability and variability across frequency bands in neural synchrony
      between primary and secondary somatosensory areas following somatosensory
      stimulation.
AB  - Objectives: To examine the temporal stability and variability of neuronal
      synchronization among the contralateral primary somatosensory cortex (cSI) and
      contralateral (cSII) and ipsilateral secondary somatosensory cortex (iSII) in
      response to median nerve stimulation. Methods: Both the spontaneous
      magnetoencephalography (MEG) signals as the pre-stimulus condition and
      somatosensory evoked magnetic-fields (SEF) were recorded in eleven healthy
      subjects. We calculated a phase-locking value (PLV) between two areas among cSI,
      cSII, and iSII in five frequency bands (theta: 5-7 Hz, alpha: 8-12 Hz, beta: 15
      29 Hz, gamma-1: 30-59 Hz, and gamma-2: 60-90 Hz), and compared the PLV among in
      pre-stimulus and stimulus conditions. Results: The PLV between cSI and cSII for
      the theta band activity varied within 2 s from the stimulus onset. On the other
      hand, the PLV between cSI and iSII for the alpha band did not vary within 2 s.
      Conclusion: The fluctuation of neuronal synchrony among sensory-related cortices
      in response to median nerve stimulation depends on the induced frequency band and
      inter-region. Significance: This study is the first to report the temporal
      characteristic of stimulus-driven neural synchrony following somatosensory
      stimulation.

PMID- 30214984
TI  - Corticobulbar motor evoked potentials from tongue muscles used as a control in
      cervical spinal surgery.
AB  - Objective: Motor evoked potentials (MEPs) changes might be caused to the non
      surgically induced factors during cervical spinal surgery. Therefore, control
      MEPs recorded cranially to the exit of the C5 root are highly recommendable in
      cervical spinal surgery. We studied whether corticobulbar MEPs (C-MEPs) from
      tongue muscle could be used as a control MEPs in cervical spinal surgery.
      Methods: Twenty-five consecutive cervical spinal surgeries were analyzed.
      Stimulation of motor area for tongue was done by subcutaneous electrodes placed
      at C3/C4 (10-20 EEG System), and recording was done from both sides of tongue.
      Results: C-MEPs were recorded successfully 24 out of the 25 (96%) tested
      patients. Forty-six out of fifty MEPs (92%) from tongue muscles were monitorable
      from the baseline. In two patients, we could obtain only unilateral C-MEPs. Mean
      MEPs latencies obtained from the left and right side of the tongue were 11.5 +/-
      1 ms and 11.5 +/- 0.8 ms, respectively. Conclusions: Monitoring C-MEPs from
      tongue muscles might be useful control in cervical spinal surgery. They were
      easily elicited and relatively free from phenomenon of peripheral stimulation of
      the hypoglossal nerves. Significance: This is first study to identify the
      usefulness of C-MEPs as a control of cervical spinal surgery.

PMID- 30214986
TI  - Limbic and new onset refractory tonic status epilepticus (NORSE) in anti-NMDAR
      encephalitis.
AB  - Aims: To present a case of anti-NMDA receptor encephalitis (anti-NMDAR) with new
      onset refractory non-convulsive status epilepticus (NORSE). Methods: Case report
      with clinical details, MRI, PET, and EEG illustrations. Results: New onset
      refractory status epilepticus (NORSE) may arise from anti-NMDAR, and offers
      diagnostic and treatment challenges for immuno-therapy and refractory status
      epilepticus. Non-convulsive status epilepticus with generalized fast activity,
      has not been reported in anti-NMDAR, in NORSE. Conclusions: A patient with anti
      NMDAR and generalized status with stiffening, right focal weakness, high
      frequency alpha/beta on EEG, brain FDG-PET/CT changes in the left temporo
      parietal regions and cerebellum was presented. We discuss the unique treatment
      challenges of anti-NMDAR. NORSE and generalized nonconvulsive status epilepticus.

PMID- 30214987
TI  - Different orthostatic hyperkinesias go "Thump".

PMID- 30214985
TI  - Proposal for best practice in the use of video-EEG when psychogenic non-epileptic
      seizures are a possible diagnosis.
AB  - The gold-standard for the diagnosis of psychogenic non-epileptic seizures (PNES)
      is capturing an attack with typical semiology and lack of epileptic ictal
      discharges on video-EEG. Despite the importance of this diagnostic test, lack of
      standardisation has resulted in a wide variety of protocols and reporting
      practices. The goal of this review is to provide an overview of research findings
      on the diagnostic video-EEG procedure, in both the adult and paediatric
      literature. We discuss how uncertainties about the ethical use of suggestion can
      be resolved, and consider what constitutes best clinical practice. We stress the
      importance of ictal observation and assessment and consider how diagnostically
      useful information is best obtained. We also discuss the optimal format of video
      EEG reports; and of highlighting features with high sensitivity and specificity
      to reduce the risk of miscommunication. We suggest that over-interpretation of
      the interictal EEG, and the failure to recognise differences between typical
      epileptic and nonepileptic seizure manifestations are the greatest pitfalls in
      neurophysiological assessment of patients with PNES. Meanwhile, under-recognition
      of semiological pointers towards frontal lobe seizures and of the absence of
      epileptiform ictal EEG patterns during some epileptic seizure types (especially
      some seizures not associated with loss of awareness), may lead to erroneous PNES
      diagnoses. We propose that a standardised approach to the video-EEG examination
      and the subsequent written report will facilitate a clear communication of its
      import, improving diagnostic certainty and thereby promoting appropriate patient
      management.

PMID- 30214988
TI  - Operation of a P300-based brain-computer interface by patients with
      spinocerebellar ataxia.
AB  - Objective: We investigated the efficacy of a P300-based brain-computer interface
      (BCI) for patients with spinocerebellar ataxia (SCA), which is often accompanied
      by cerebellar impairment. Methods: Eight patients with SCA and eight age- and
      gender-matched healthy controls were instructed to input Japanese hiragana
      characters using the P300-based BCI with green/blue flicker. All patients
      depended on some assistance in their daily lives (modified Rankin scale: mean
      3.5). The chief symptom was cerebellar ataxia; no cognitive deterioration was
      present. A region-based, two-step P300-based BCI was used. During the P300 task,
      eight-channel EEG data were recorded, and a linear discriminant analysis
      distinguished the target from other nontarget regions of the matrix. Results: The
      mean online accuracy in BCI operation was 82.9% for patients with SCA and 83.2%
      for controls; no significant difference was detected. Conclusion: The P300-based
      BCI was operated successfully not only by healthy controls but also by
      individuals with SCA. Significance: These results suggest that the P300-based BCI
      may be applicable for patients with SCA.

PMID- 30214990
TI  - Ketogenic diet: Old treatment, new beginning.

PMID- 30214989
TI  - The role for ketogenic diets in epilepsy and status epilepticus in adults.
AB  - Ketogenic diet (KD) therapies are high fat, low carbohydrate diets designed to
      mimic a fasting state. Although studies demonstrate KD's success in reducing
      seizures stretching back nearly a century, the last 25 years have seen a
      resurgence in diet therapy for the management of drug-resistant epilepsy in
      children as well as adults. With >=50% seizure reduction efficacy rates in adults
      of 22-55% for the classic KD and 12-67% for the modified Atkins diet, diet
      therapy may be in many instances comparable to a trial of an additional anti
      epileptic medication and potentially with fewer side effects and other health
      benefits. Moreover, ketogenic diets offer promising new adjunctive strategies for
      the treatment of acute status epilepticus in the intensive care setting. Here, we
      review the efficacy and utility of ketogenic diets for the management of chronic
      epilepsy and refractory status epilepticus in adults and offer practical
      guidelines for diet implementation and maintenance.

PMID- 30214991
TI  - High-resistance strength training does not affect nerve cross sectional area - An
      ultrasound study.
AB  - Objective: The aim was to study the effect of high-resistance strength training
      on peripheral nerve morphology, by examining properties of peripheral nerves as
      well as distal and proximal muscle thickness with ultrasound, comparing healthy
      individuals who perform and do not perform high-resistance strength training.
      Methods: Neuromuscular ultrasound was used to examine cross sectional area (CSA)
      of the median and musculocutaneous nerves, and muscle thickness of the abductor
      pollicis brevis muscle, biceps brachii muscle, quadriceps muscle and extensor
      digitorum brevis muscle, in 44 healthy individuals, of whom 22 performed regular
      high-resistance strength training. Results: No difference in nerve CSA was found
      between trained and untrained individuals although trained individuals had
      thicker biceps brachii muscles. The CSA of the median nerve in the forearm
      correlated with participants' height and was significantly larger in men than
      women. Conclusions: In this cohort, CSA of the median and musculocutaneous nerves
      was not affected by strength training, whereas gender had a prominent effect both
      on CSA and muscle thickness. Significance: This is the first study to examine the
      effect of high-resistance strength training on peripheral nerves with
      neuromuscular ultrasound.

PMID- 30214992
TI  - A revised glossary of terms most commonly used by clinical
      electroencephalographers and updated proposal for the report format of the EEG
      findings. Revision 2017.

PMID- 30214993
TI  - Median nerve ultrasonography in carpal tunnel syndrome.

PMID- 30214994
TI  - Standard median nerve ultrasound in carpal tunnel syndrome: A retrospective
      review of 1,021 cases.
AB  - Objective: Carpal tunnel syndrome (CTS) is diagnosed with electrodiagnostic (EDx)
      studies. Investigations have examined US cross sectional-area (CSA) and wrist to
      forearm ratio (WFR) cut-offs for screening EDx abnormalities in patients with
      suspected CTS. The objective of this study is to determine if these US parameters
      are effective in a real world population. Methods: This is a retrospective review
      of patients presenting to the Duke Electromyography (EMG) Laboratory during 2013
      2014 with a final diagnosis of CTS. US diagnosis of CTS was based upon median
      nerve cross-sectional area of >9 mm2 and/or wrist-to-forearm ratio of >1.4. EDx
      studies were the gold standard for diagnosis. Results: A total of 670 patients
      and 1,021 extremities were studied. US was positive in 97.6% of EDx confirmed
      CTS. Conclusion: Median nerve US is nearly as sensitive as the gold standard for
      EDx testing for the diagnosis of CTS. Significance: The data here suggest that US
      may have use as a screening tool prior to performing EDx testing for CTS.

PMID- 30214995
TI  - Functional localization and effective connectivity of cortical theta and alpha
      oscillatory activity during an attention task.
AB  - Objectives: The aim of this paper is to investigate cortical electric neuronal
      activity as an indicator of brain function, in a mental arithmetic task that
      requires sustained attention, as compared to the resting state condition. The two
      questions of interest are the cortical localization of different oscillatory
      activities, and the directional effective flow of oscillatory activity between
      regions of interest, in the task condition compared to resting state. In
      particular, theta and alpha activity are of interest here, due to their important
      role in attention processing. Methods: We adapted mental arithmetic as an
      attention ask in this study. Eyes closed 61-channel EEG was recorded in 14
      participants during resting and in a mental arithmetic task ("serial sevens
      subtraction"). Functional localization and connectivity analyses were based on
      cortical signals of electric neuronal activity estimated with sLORETA
      (standardized low resolution electromagnetic tomography). Functional localization
      was based on the comparison of the cortical distributions of the generators of
      oscillatory activity between task and resting conditions. Assessment of effective
      connectivity was based on the iCoh (isolated effective coherence) method, which
      provides an appropriate frequency decomposition of the directional flow of
      oscillatory activity between brain regions. Nine regions of interest comprising
      nodes from the dorsal and ventral attention networks were selected for the
      connectivity analysis. Results: Cortical spectral density distribution comparing
      task minus rest showed significant activity increase in medial prefrontal areas
      and decreased activity in left parietal lobe for the theta band, and decreased
      activity in parietal-occipital regions for the alpha1 band. At a global level,
      connections among right hemispheric nodes were predominantly decreased during the
      task condition, while connections among left hemispheric nodes were predominantly
      increased. At more detailed level, decreased flow from right inferior frontal
      gyrus to anterior cingulate cortex for theta, and low and high alpha
      oscillations, and increased feedback (bidirectional flow) between left superior
      temporal gyrus and left inferior frontal gyrus, were observed during the
      arithmetic task. Conclusions: Task related medial prefrontal increase in theta
      oscillations possibly corresponds to frontal midline theta, while parietal
      decreased alpha1 activity indicates the active role of this region in the
      numerical task. Task related decrease of intracortical right hemispheric
      connectivity support the notion that these nodes need to disengage from one
      another in order to not interfere with the ongoing numerical processing. The
      bidirectional feedback between left frontal-temporal-parietal regions in the
      arithmetic task is very likely to be related to attention network working memory
      function. Significance: The methods of analysis and the results presented here
      will hopefully contribute to clarify the roles of the different EEG oscillations
      during sustained attention, both in terms of their functional localization and in
      terms of how they integrate brain function by supporting information flow between
      different cortical regions. The methodology presented here might be clinically
      relevant in evaluating abnormal attention function.

PMID- 30214996
TI  - Neurophysiology contributes to outcome prediction after cardiac arrest.
AB  - This "Points of View" paper discusses the role of neurophysiology in predicting
      outcome in patients who have initially survived a cardiac arrest but remain in
      coma. The authors, from different clinical backgrounds, discuss their individual
      approaches to neuroprognostication.

PMID- 30214997
TI  - Connectome: Graph theory application in functional brain network architecture.
AB  - Network science and graph theory applications have recently spread widely to help
      in understanding how human cognitive functions are linked to neuronal network
      structure, thus providing a conceptual frame that can help in reducing the
      analytical brain complexity and underlining how network topology can be used to
      characterize and model vulnerability and resilience to brain disease and
      dysfunction. The present review focuses on few pivotal recent studies of our
      research team regarding graph theory application in functional dynamic
      connectivity investigated by electroencephalographic (EEG) analysis. The article
      is divided into two parts. The first describes the methodological approach to EEG
      functional connectivity data analysis. In the second part, network studies of
      physiological aging and neurological disorders are explored, with a particular
      focus on epilepsy and neurodegenerative dementias, such as Alzheimer's disease.

PMID- 30214998
TI  - Standardization of the Jendrassik maneuver in Achilles tendon tap reflex.
AB  - Objective: For many decades, the Jendrassik maneuver (JM) has been used as a
      reinforcement for stretch reflexes, although the underlying mechanism of this
      reinforcement is still not fully understood. Moreover, the term JM has been used
      for many different muscle contraction strategies as there is no fixed movement
      for the maneuver in the literature. In this study, we aimed to investigate the
      effects of clenched hand pull, teeth clenching, and their combined effects to
      reach standardization. Methods: Achilles tendon tap reflex responses in the
      soleus were recorded during rest (R), hand pull (HP), teeth clench (TC), and HP +
      TC combined, hereafter referred to as the JM. Results: Reflex response amplitudes
      significantly increased during JM, HP, and TC in the soleus. HP and JM
      significantly changed the background activity in the soleus, but TC alone did
      not. Conclusion: These results suggest that dominantly presynaptic disinhibitory
      mechanisms may be responsible for the increase in the tendon tap reflex during
      HP, TC, and JM. Significance: Because the findings indicate that HP increases the
      background activity of the soleus, we suggest that researchers should use only TC
      during the Jendrassik maneuver to avoid any confounding background activity
      change.

PMID- 30214999
TI  - Large fasciculation can clinically manifest as spinal myoclonus;
      electromyographic and dynamic echomyographic studies of four cases with motor
      neuron disease.
AB  - Objective: Patients with motor neuron disease rarely present with fasciculation
      which is large enough to be clinically recognized as myoclonus. This study is
      aimed at elucidating the features of large fasciculation manifesting as myoclonus
      by using surface electromyography (surface EMG) and dynamic echomyography
      (dynamic Echo). Methods: Four patients with amyotrophic lateral sclerosis, two of
      whom clinically presented with both fasciculation and myoclonus, were studied by
      using the surface EMG and the dynamic Echo. Results: At rest, all patients had
      fasciculation in atrophic muscles, and the surface EMG showed occasional
      discharges of different waveforms corresponding to fasciculation. During
      voluntary gentle muscle contraction, the surface EMG showed repetitive discharges
      in the contracting muscle, which were constant in size and waveform within each
      muscle. The muscle Echo at rest revealed occasional contractions of a small
      number of muscle fibers corresponding to fasciculation. During voluntary muscle
      contraction, the number of muscle fibers involved in the involuntary motor
      phenomena was larger in the patients who clinically presented with myoclonus
      compared with other patients who clinically presented only with fasciculation. In
      a patient who presented with myoclonus, there was no contraction in the
      antagonist muscle. Conclusions: Fasciculation involving a large number of muscle
      fibers clinically manifests as spinal myoclonus. Significance: Fasciculation
      involving a large number of muscle fibers can be a cause of spinal myoclonus.

PMID- 30215001
TI  - Full 10-20 EEG application in hospitalised neonates is not associated with an
      increase in stress hormone levels.

PMID- 30215002
TI  - Differentiating fasciculations from myoclonus in motor neuron disease.

PMID- 30215003
TI  - The effect of stimulation rate on cervical vestibular evoked myogenic potential
      quality.

PMID- 30215000
TI  - Usefulness of EEG for the differential diagnosis of possible transient ischemic
      attack.
AB  - Objective: EEG value in possible transient ischemic attacks (TIA) is unknown. We
      aim to quantify focal slow wave activity (FSWA) and epileptiform activity (EA)
      frequency in possible TIA, and to analyse its contribution to the final diagnosis
      of seizures and/or definitive TIA. Methods: Prospective longitudinal study of
      possible TIA patients evaluated at a tertiary centre during 36 months and with 1
      3 months follow-up. EEG was performed as soon as possible (early EEG) and one
      month later (late EEG). A stroke neurologist established final diagnosis after
      reassessing all clinical and diagnostic tests. Results: 80 patients underwent an
      early EEG (45.8 h after possible TIA): 52 had FSWA and 6 of them also EA. Early
      FSWA was associated with epileptic seizure or definitive TIA final diagnosis (p =
      .041). Patients with these diagnoses had more frequently early FSWA (19/23;
      82.6%) than EA (6/23; 26.1%). 6/13 (46.2%) patients with epileptic seizure final
      diagnosis had EA.In the late EEG, 43 (58.1%) patients demonstrated persistent
      FSWA and 3 of them also EA. Persistent FSWA in the late EEG was more frequent in
      seizures than in TIA patients (91.7% vs. 45.5%). FSWA disappearance was
      associated with acute vascular lesion on neuroimage. Conclusions: FSWA was the
      commonest EEG abnormality found in the early EEG of patients with possible TIA,
      but did not distinguish between TIA and seizure patients. In patients with
      seizures, FSWA was more common than EA and its presence in the late EEG was more
      likely in patients with epileptic seizures than with TIA. Significance: The
      majority of possible TIA patients with the final diagnosis of epileptic seizures
      do not have EA in the early or late EEG.

PMID- 30215004
TI  - Phenomenology of neurophysiologic changes during surgical treatment of carotid
      stenosis using signal analysis.
AB  - Objective: To describe the changes in the shape and topology of the somatosensory
      evoked potential (SSEP) during carotid endarterectomy, with particular reference
      to the time of clamping. Methods: Routine intraoperative monitoring was performed
      on 30 patients undergoing carotid endarterectomy (15) or undergoing stenting (15)
      using median nerve SSEPs. Post-operatively the first and second derivatives of
      the potential were examined. Separate analysis of the SSEP using wavelets was
      also performed. Results: In no instances did changes in the SSEP reach clinical
      significance. The first derivative showed significant changes that were
      temporally related to the clamp period. After clamping the 'velocity' was higher
      than baseline. There were changes in the wavelets related to the clamp period
      with more marked spectral edges at the conclusion of the procedure than baseline.
      In all instances the patient had a good clinical outcome. Conclusions: Wavelet
      and derivative analysis of evoked potentials show changes that are not apparent
      with measures of amplitude and latency. The clinical relevance of these changes
      remains uncertain and await larger studies. Significance: Increased velocity and
      spectral edges may be markers of increased cerebral blood flow, at least in the
      setting of pre-existing carotid stenosis.

PMID- 30215005
TI  - Vibrotactile and thermal perception and its relation to finger skin thickness.
AB  - Objective: Quantitative measurements of vibrotactile and thermotactile perception
      thresholds (VPT and TPT, respectively) rely on responses from sensory receptors
      in the skin when mechanical or thermal stimuli are applied to the skin. The
      objective was to examine if there is a relation between skin thickness (epidermis
      and dermis) and VPT or TPT. Methods: Perception thresholds were measured on the
      volar side of the fingertip on 148 male subjects, out of which 116 were manual
      workers exposed to hand-transmitted vibration and 32 were white-collar (office)
      workers. Skin thickness was measured using a high-frequency ultrasonic derma
      scanner system. Results: The difference in age, perception thresholds and skin
      thickness between manual and office workers was small and non-significant except
      for the perception of cold, which was decreased by vibration exposure. Skin
      thickness for both subgroups was mean 0.57 mm (range 0.25-0.93 mm). Increased age
      was associated with decreased perception of warmth and vibration. Lifetime
      cumulative exposure to vibration, but not age, was associated with decreased
      perception of cold. Conclusion: No association (p > .05) was found between finger
      skin thickness in the range of about 0.1-1 mm and vibration perception threshold
      for test frequencies from 8 to 500 Hz and thermotactile perception thresholds for
      warmth and cold. Increasing age was associated with reduced perception of
      vibration and warmth. Vibration exposure was associated with decreased perception
      of cold. Significance: Skin thickness is a factor that may affect the response
      from sensory receptors, e.g., due to mechanical attenuation and thermal
      insulation. Thus, to evaluate perception threshold measurements, it is necessary
      to know if elevated thresholds can be attributed to skin thickness. No previous
      studies have measured skin thickness as related to vibrotactile and thermotactile
      perception thresholds. This study showed no association between skin thickness
      and vibrotactile perception or thermotactile perception.

PMID- 30215006
TI  - Evidence of neurophysiological improvement of early manifestations of small-fiber
      dysfunction after liver transplantation in a patient with familial amyloid
      neuropathy.
AB  - Introduction: Small fiber polyneuropathy (SFP) is a common heralding clinical
      manifestation of damage to the nervous system in patients with familial
      amyloidosis. The diagnosis of SFP is a significant factor in the decision to
      treat a previously asymptomatic gene carrier, as treatment would prevent
      irreversible nerve damage. This requires detection of the earliest but
      unequivocal signs of peripheral nerve involvement. Case report: We present the
      case of a young female who was diagnosed of SFP, supported by data from
      quantitative sensory testing. She had preserved sensory nerve action potentials
      in the distalmost nerves of her feet and recordable nociceptive evoked
      potentials. She was successfully transplanted the liver from a previously healthy
      donor, and recovered fully of her symptoms and signs. Improvement was documented
      with repeated psychophysical and electrodiagnostic testing in the course of 4
      years after transplantation. Significance: This case illustrates the utility of
      psychophysical testing to support the diagnosis of SFP.

PMID- 30215007
TI  - Gender, side to side and BMI differences in long thoracic nerve conduction
      velocity: A novel technique.
AB  - Objectives: The purpose of this study was to describe a new technique to record
      long thoracic nerve conduction velocity through the axilla as well as to assist
      in establishing normative values for latency and amplitude of the long thoracic
      nerve and to evaluate side to side, gender and BMI differences. Methods: 26
      healthy subjects (12 males/14 females) participated in the study with data
      collected bilaterally resulting in 52 limbs studied. Surface recording was over
      the serratus anterior muscle with the recording electrode located on the rib
      closest to a distance within a standardized range of 22-24 cm distal to the
      acromion. Stimulation was delivered at the mid axillary line, then again in the
      supraclavicular region. A caliper was used to measure the distance between the
      two stimulation sites in order to calculate the nerve conduction velocity.
      Results: The normal value (mean + 2 SD) for distal latency is <2.7 msec, while
      the normal value for velocity (mean - 2 SD) is >61.0 m/s. Absolute amplitude
      values were not calculated. Side to side difference normal values for distal
      latency, amplitude and velocity are 0.7 msec, 70.3% and 8.5% respectively. A two
      way analysis of variance (ANOVA) revealed a significant gender and BMI difference
      in both distal (0.02) and proximal amplitude (0.05) means. There was no
      significant interaction between gender and BMI for latency or velocity values for
      either stimulation site. Conclusions: The distal latency values are not
      significantly different from those reported previously, however long thoracic
      nerve conduction velocity has not been described before and would be an
      appropriate way to monitor velocity through the proximal portions of the brachial
      plexus. Men who qualified as overweight with a BMI greater than 25 demonstrated a
      larger amplitude when compared with average weight men and women. In contrast
      women with BMI greater than 25 demonstrated a much smaller amplitude when
      compared with overweight men and average weight men and women. Significance:
      Absolute amplitude normal values are not reported as BMI may impact the ability
      to record an accurate amplitude for both men and women. Long thoracic nerve
      conduction velocity and latency appear to be more reliable measures.

PMID- 30215008
TI  - Static magnetic field stimulation applied over the cervical spinal cord can
      decrease corticospinal excitability in finger muscle.
AB  - Objective: Transcranial static magnetic field stimulation has recently been
      demonstrated to modulate cortical excitability. In the present study, we
      investigated the effect of transspinal static magnetic field stimulation (tsSMS)
      on excitability of the corticospinal tract. Methods: A compact magnet for tsSMS
      (0.45 Tesla) or a stainless steel cylinder for sham stimulation was positioned
      over the neck (C8 level) of 24 able-bodied subjects for 15 min. Using 120% of the
      resting motor threshold transcranial magnetic stimulation intensity, motor evoked
      potentials (MEPs) were measured from the first digital interosseous muscle
      before, during, and after the tsSMS or sham intervention. Results: Compared with
      baseline MEP amplitudes were decreased during tsSMS, but not during sham
      stimulation. Additionally, during the intervention, MEP amplitudes were lower
      with tsSMS than sham stimulation, although these effects did not last after the
      intervention ceased. Conclusions: The results suggest that static magnetic field
      stimulation of the spinal cord by a compact magnet can reduce the excitability of
      the corticospinal tract. Significance: Transspinal static magnetic field
      stimulation may be a new non-invasive neuromodulatory tool for spinal cord
      stimulation. Its suppressive effect may be applied to patients who have
      pathological hyperexcitability of the spinal neural network.

PMID- 30215009
TI  - Influence of placement sites of the active recording electrode on CMAP
      configuration in the trapezius muscle.
AB  - Objective: We investigated how the active electrode placement site influences
      compound muscle action potential (CMAP) configuration of the upper trapezius
      muscle (TM). Methods: A nerve conduction study of the accessory nerve was
      performed, and the CMAPs obtained with two different placement sites, i.e.,
      placement of the active recording electrode on the belly of the upper TM (CMAP-A)
      and placement of the electrode 2 cm behind the belly (CMAP-B), were compared.
      CMAPs were also obtained with the active recording electrode placed in the
      supraspinous fossa (CMAP-C). Results: All CMAPs were recorded from 21 healthy
      volunteers. The mean peak-to-peak amplitude of CMAP-B was 3.4 mV higher than that
      of CMAP-A (11.0 +/- 4.0 mV vs. 14.4 +/- 4.9 mV; P < 0.01). The mean peak-to-peak
      amplitude of CMAP-C was 10.3 +/- 5.0 mV. Conclusions: CMAP of the upper TM was
      always higher when the active recording electrode was placed 2 cm behind the
      belly of the muscle. Significance: When stimulating the accessory nerve, a
      current spread occurs to the C5 spinal nerve root and another CMAP originating
      from the supraspinatus muscle occurs in the supraspinous fossa. The volume
      conduction from the supraspinatus muscle affects the active recording electrode
      on the TM, resulting in an increase in CMAP amplitude.

PMID- 30215010
TI  - Visual EEG reviewing times with SCORE EEG.
AB  - Objective: Visual EEG analysis is the gold standard for clinical EEG
      interpretation and analysis, but there is no published data on how long it takes
      to review and report an EEG in clinical routine. Estimates of reporting times may
      inform workforce planning and automation initiatives for EEG. The SCORE standard
      has recently been adopted to standardize clinical EEG reporting, but concern has
      been expressed about the time spent reporting. Methods: Elapsed times were
      extracted from 5889 standard and sleep-deprived EEGs reported between 2015 and
      2017 reported using the SCORE EEG software. Results: The median review time for
      standard EEG was 12.5 min, and for sleep deprived EEG 20.9 min. A normal standard
      EEG had a median review time of 8.3 min. Abnormal EEGs took longer than normal
      EEGs to review, and had more variable review times. 99% of EEGs were reported
      within 24 h of end of recording. Review times declined by 25% during the study
      period. Conclusion: Standard and sleep-deprived EEG review and reporting times
      with SCORE EEG are reasonable, increasing with increasing EEG complexity and
      decreasing with experience. EEG reports can be provided within 24 h.
      Significance: Clinical standard and sleep-deprived EEG reporting with SCORE EEG
      has acceptable reporting times.

PMID- 30215011
TI  - Diagnostic utility of eight-channel EEG for detecting generalized or hemispheric
      seizures and rhythmic periodic patterns.
AB  - Objectives: To compare the diagnostic utility of electroencephalography (EEG)
      using reduced, 8-channel montage (rm-EEG) to full, 18-channel montage (fm-EEG)
      for detection of generalized or hemispheric seizures and rhythmic periodic
      patterns (RPPs) by neurologists with extensive EEG training, neurology residents
      with minimal EEG exposure, and medical students without EEG experience. Methods:
      We presented EEG samples in both fm-EEG (bipolar montage) and rm-EEG (lateral
      leads of bipolar montage) to 20 neurologists, 20 residents, and 42 medical
      students. Unanimous agreement of three senior epileptologists defined samples as
      seizures (n = 7), RPPs (n = 10), and normal or slowing (n = 20). Differences in
      median accuracy, sensitivity, and specificity were assessed using Wilcoxon signed
      rank tests. Results: Full and reduced EEG demonstrated similar accuracy when read
      by neurologists (fm-EEG: 95%, rm-EEG: 95%, p = 0.29), residents (fm-EEG: 80%, rm
      EEG: 80%, p = 0.05), and students (fm-EEG: 60%, rm-EEG: 51%, p = 0.68). Moreover,
      neurologists' sensitivity for detecting seizure activity was comparable between
      fm-EEG (100%) and rm-EEG (98%) (p = 0.17). Furthermore, the specificity of rm-EEG
      for seizures and RPP (neurologists: 100%, residents: 90%, students: 86%) was
      significantly greater than that of fm-EEG (neurologists: 93%, p = 0.03;
      residents: 80%, p = 0.01; students: 69%, p < 0.001). Conclusions: The reduction
      of the number of EEG channels from 18 to 8 does not compromise neurologists'
      sensitivity for detecting seizures that are often a core reason for performing
      urgent EEG. It may also increase their specificity for detecting rhythmic and
      periodic patterns, and thereby providing important diagnostic information to
      guide patient's management. Significance: Our study is the first to document the
      utility of a reduced channel EEG above the hairline compared to full montage EEG
      in aiding medical staff with varying degrees of EEG training to detect
      generalized or hemispheric seizures.

PMID- 30215012
TI  - Clinical utility of contact heat evoked potentials (CHEPs) in a case of mentalis
      nerve lesion.
AB  - Objective: Nociceptive evoked potentials are still infrequently used in
      electrodiagnostic studies of single patients. We report a case in which the
      results of contact heat evoked potentials (CHEPs) provided unique information for
      the diagnosis. Methods: After biopsy for a local cementoma, a 21-year-old woman
      presented with neuropathic pain in the distribution of her left mentalis nerve. A
      CT scan showed a well circumscribed lesion near the mentalis nerve groove. We
      examined brainstem reflexes and evoked potentials conveyed through the mentalis
      nerve. Results: Blink reflex responses recorded from the orbicularis oculi, jaw
      jerk and masseteric silent period recorded from the masseter muscles and long
      latency evoked potentials recorded from Cz to electrical stimulation of the
      mentalis nerve were all within normal values, with no differences between sides.
      However, CHEPs, recorded from Cz to thermoalgesic stimulation of the left
      mentalis area were decreased to approximately 1/3 their size in comparison to
      stimulation to the unaffected side. Conclusion: While the patient reported
      symptoms and had neuroimaging signs of mentalis neuropathy, the sole
      electrophysiological abnormality identified was that of CHEPs, which specifically
      test small, unmyelinated fibers. Significance: Nociceptive evoked potentials can
      provide unique information on damage of small nerve fibers in specific cases.

PMID- 30215014
TI  - Electrodiagnosis, a real added value for the evaluation of upper limb
      paresthesiae and pains.

PMID- 30215015
TI  - Cerebral blood flow changes during tilt table testing in healthy volunteers, as
      assessed by Doppler imaging of the carotid and vertebral arteries.
AB  - Objectives: Using different techniques, reduction of cerebral blood flow (CBF)
      during orthostatic stress were demonstrated. One study reported flow reduction of
      the right internal carotid (ICA) and vertebral (VA) artery during orthostatic
      stress by Doppler imaging, with different effects on the 2 vessels. Global CBF
      changes, using this technique, have not been reported. Therefore, flow of the
      ICA, VA and global CBF were measured during head-up tilt testing. Methods: 33
      healthy volunteers underwent tilt testing. At three time points (supine, half way
      and at the end of the test) Doppler imaging of the ICA and VA was performed, as
      well as PetCO2 measurements. Results: Global CBF was significantly reduced by 4.5
      +/- 2.8% halfway the test and by 6.0 +/- 3.4% at the end. All 4 artery flows were
      significantly reduced during the tilt, without differences between them. Despite
      small changes in PetCO2 there was a significant relation between de CBF decrease
      and PetCO2 decrease (p < 0.05). Conclusions: Orthostatic stress in HV results in
      a small but significant reduction of CBF by a homogenous reduction in the four
      cerebral vessels and is modulated by PetCO2 changes. Significance: CBF changes
      can be measured during tilt testing using Doppler VA and ICA imaging.

PMID- 30215013
TI  - Nerve conduction studies and EMG in carpal tunnel syndrome: Do they add value?
AB  - This paper summarises the views of four experts on the place of
      neurophysiological testing (EDX) in patients presenting with possible carpal
      tunnel syndrome, in guiding their treatment, and in reevaluations. This is not
      meant to be a position paper or a literature review, and heterogeneous viewpoints
      are presented. Nerve conduction studies should be performed in patients
      presenting with possible carpal tunnel syndrome to assist diagnosis, and may need
      to be repeated at intervals in those managed conservatively. There is evidence
      that local corticosteroid injection is safe and effective for many patients,
      thereby avoiding or deferring surgical decompression. All patients should undergo
      EDX studies before any invasive procedure for CTS (injection or surgery). Needle
      EMG studies are not obligatory, but may be needed in those with severe disease
      and those in whom an alternate or concomitant diagnosis is suspected.

PMID- 30215017
TI  - EMG indications and findings in a sub-Saharan African neurorehabilitation center.
AB  - Objective: This study aims to assess the frequency and indication for
      electrodiagnostic referrals as well as to summarize the findings from the
      procedure at a neurorehabilitation center in Ibadan, Nigeria. Methods: This is a
      retrospective cross-sectional study. Data from referrals to Blossom Medical
      Centre/World Federation for Neurorehabilitation (BMC/WFNR) center, Ibadan,
      Nigeria, from April 2014 to December 2016 were collated and analyzed. Results:
      Sixty referrals were received during the period of evaluation. Neurologists
      referred most of the patients (47; 71.7%). Disorders of the peripheral nerves
      were the most frequent reasons for electromyography (EMG), and they were the most
      common electrodiagnosis with better classified into axonal and demyelinating
      types. The overall congruence between the suspected diagnosis and final diagnosis
      was 58.3%. Requests by neurologists were significantly more appropriate than
      those by other specialists (p value = 0.02). Conclusion: Polyneuropathy,
      entrapment neuropathy, and disorders of the motor nerve root and plexus were the
      most common reasons for electrodiagnostic requests, and the majority of the
      referrals were from neurologists. Significance: EMG has changed the approach
      towards the diagnosis and management of neuromuscular disorders in Nigeria. It is
      hoped that with more neurophysiology education in this environment,
      neurophysiological practice will become widely available.

PMID- 30215016
TI  - A rare case of isolated myoclonus in an elderly male without a history of
      epilepsy.
AB  - Aim: Through this case report we attempt to highlight the presentation, initial
      investigation and management of lingual myoclonus as well as consolidate relevant
      literature. Case: We present a unique case of a 72-year-old man who was admitted
      to the hospital for a sudden onset episodic speech arrest. Lingual myoclonus, an
      isolated movement disorder, manifested as an intermittent expressive aphasia
      secondary to the intrusion-protrusion movements of his tongue. During this time,
      the patient remained conscious and was able to continue to follow commands.
      Initial diagnostic evaluation with a CT scan, MRI and EEG failed to illicit a
      clear underlying etiology and the patient was empirically treated with valproic
      acid with complete resolution of his symptoms. Discussion: This unusual
      presentation represents a rare disorder which is not well described in
      literature. Initial evaluation of which required excluding associated etiologies
      including strokes, seizures, medications/toxins or CNS infections. Without a
      clear etiology on initial diagnostic evaluation, the patient was empirically
      treated as no clear guidelines exist. This case presentation is an attempt to add
      to the current understanding of lingual myoclonus.

PMID- 30215018
TI  - Holmes' or functional tremor?
AB  - Objective: Holmes tremor is a rare kind of hyperkinetic movement disorder,
      clinically characterized by irregular, monolateral, high-amplitude jerks, sharing
      a quite similar frequency with those observed in Parkinson's disease; its
      generation likely relies on a combined involvement of cerebello-thalamic and
      nigrostriatal pathways. Methods: We report the case of a man with a combined
      resting-postural-kinetic tremor. Neuroimaging revealed an intracranial dermoid
      cyst at the right pontocerebellar angle with brainstem dislocation. We performed
      an extensive electrophysiological assessment from the extensor digitorum communis
      (EDC) and flexor carpi radialis (FCR) muscles. Results: Both the spontaneous
      variability of tremor frequency and frequency entrainment argued against an
      organic aetiology. Polymyography revealed: 1) a paradoxical increase of tremor
      amplitude with mass loading; 2) jerks' synchronization between antagonistic
      muscles during voluntary contralateral motor performances; 3) tremor inhibition
      while asking the patient to make a ballistic movement. Conclusions: We suggest a
      complete psychogenic genesis or, at least in part, a possible co-existence of a
      rubral tremor with functional traits. Significance: Here, we propose a simple and
      fast test battery for an early diagnosis of functional tremor. Our results prompt
      further studies to re-define electrodiagnostic criteria in hyperkinetic movement
      disorders, possibly updating the floating border between organic and psychogenic
      disease.

PMID- 30215021
TI  - Responsive neurostimulation for epilepsy: More than stimulation.

PMID- 30215019
TI  - Mirror movements or functional tremor masking organic tremor.
AB  - Background: Functional tremors can be diagnosed based on clinical and physiologic
      criteria such as entrainment, suggestibility, distractibility, variable nature
      with the associated clinical history of psychosomatic co-morbidities. The current
      case report highlights the underrecognized utility of neurophysiology in the
      correct diagnosis of tremors, providing useful clinical and neurophysiologic
      insights into clinical and physiological assessment of tremors. Case report: A 62
      year-old woman with a past medical history of polio was referred by a movement
      disorders neurologist for evaluation of tremor with concerns of a likely
      functional etiology. On first assessment there were findings notable for a
      possible organic etiology, but upon subsequent evaluation the tremor was noted to
      be variable and entrainable, suggestive of a functional etiology.
      Neurophysiological tremor study could identify an underlying organic tremor
      (likely of multi-factorial etiology). Tremor entrainment with contralateral hand
      tapping could be mirror movements or functional movements, as the underlying
      organic tremor was not entrained. The amplitude of mirrored movement was
      commensurate with the tapping amplitude. Discussion: Functional tremors may mask
      an underlying organic tremor. Additionally, motor overflow which may happen
      especially with large amplitude movements may masquerade as mirror movements,
      which can be difficult to differentiate from an entrained functional tremor.
      Objective physiology and refinement of the current clinical and physiologic
      tremor evaluation techniques may help identify an underlying organic etiology.

PMID- 30215020
TI  - A quantitative EEG and MRI analysis of intermittent temporal slowing in the
      elderly.
AB  - Objective: Whereas the correlation between diffuse slowing of EEG activity and
      neurodegenerative diseases such as Alzheimer's disease is well established,
      intermittent slowing over the temporal regions, which is a frequent finding in
      the elderly, does not have a specific clinical correlate. In this study, we
      compared quantitative EEG parameters between patients with temporal slowing with
      no signs of neurological disease and controls to evaluate cortical function in
      the temporal lobes and other cerebral regions. We also compared the width of the
      temporal lobes on magnetic resonance imaging (MRI). Methods: Mean dominant
      frequency and relative power in delta, theta, alpha, and beta frequency bands
      were examined in 20 patients older than 60 years with intermittent temporal
      slowing and 20 age-matched controls without significant lesions on MRI or medical
      conditions known to affect the EEG. Furthermore, the correlation between the
      frequency of temporal slowing and the mean dominant frequency and the width of
      the medial temporal lobes on MRI were examined. Results: Mean dominant frequency
      and the relative power in the beta frequency band was lower in patients with
      temporal slowing than in controls in all of the cortical regions examined. No
      significant correlation was found between the frequency of slowing and the mean
      dominant frequency. There was no significant difference in the width of the
      medial temporal lobes. Conclusions: Intermittent temporal slowing was correlated
      with diffusely reduced mean dominant frequency and a shift in relative power to
      lower frequency bands. Significance: The results suggest that subclinical diffuse
      cerebral pathology may be present in subjects with intermittent temporal slowing,
      but prospective studies including tests of cognitive function, cerebral
      perfusion, metabolic status, and advanced neuroimaging should be conducted.

PMID- 30215022
TI  - Evaluation of SEPs in asphyxiated newborns using a 4-electrode aEEG brain
      monitoring set-up.
AB  - Objective: To evaluate the reliability of recording cortical somatosensory evoked
      potentials (SEPs) in asphyxiated newborns using the 4-electrode setup applied in
      routine long-term amplitude-integrated EEG (aEEG) brain monitoring and to assess
      the number of averages needed for reliably detecting the cortical responses.
      Methods: We evaluated median nerve SEPs in 50 asphyxiated full-term newborns. The
      SEP interpretation (present or absent) from the original recordings with 21
      electrodes and approximately 600 trials served as the reference. This was
      compared to SEP classification (absent, present, or unreliable) based on a
      reduced (300 or 150) number of averages, and to classification based on only four
      electrodes (F3, P3, F4, P4). Results: Compared to the original classification,
      cortical SEPs were uniformly interpreted as present or absent in all 50 newborns
      with the 4-electrode setup and 600 averages. Reducing number of averages to 300
      still resulted in correct SEP interpretation in 49/50 newborns with 21-electrode
      setup, and 46/50 newborns with 4-electrode setup. Conclusions: Evaluation of
      early cortical neonatal SEPs is reliable from the 4-electrode setup commonly used
      in aEEG monitoring. SEP is discernible in most newborns with 300 averages.
      Significance: Adding SEP into routine aEEG monitoring offers an additional tool
      for early neonatal neurophysiological evaluation.

PMID- 30215023
TI  - Modified motor unit number index (MUNIX) algorithm for assessing excitability of
      alpha motor neuron in spasticity.
AB  - Objective: The understanding of the spasticity mechanism is still a problem in
      the literature, as its definition can be made on the basis of more than one
      parameter. Therefore, we studied alpha motor neuron excitability, dynamic changes
      based on force production, and patellar tendon (T) reflex in spasticity and
      healthy control groups. Methods: Alpha motor neuron excitability, force
      production, and patellar T reflex were evaluated through three different test
      protocols. Motor Unit Number Index (MUNIX) measurement was applied for
      understanding motor neuron pool properties in the first protocol. Voluntary force
      production and patellar T reflex parameters were evaluated by voluntary force
      production and triggering patellar T reflex. Twenty spasticity and 20 healthy
      volunteers participated in the study. Results: In the spasticity group, both
      MUNIX numbers and Motor Unit Size Index (MUSIX) numbers were lower than those in
      the control group. The results for the Ideal Case Motor Unit Count (ICMUC)
      parameter show that there is no significant difference between spasticity and
      healthy individuals for low-level contractions, whereas there is a significant
      difference for high-level contractions (p < 0.05). In the spasticity group, an
      increase was observed in the ratio of maximal voluntary force to the T reflex
      triggered force production (Tf/Vf). Conclusion: Spasticity and healthy subjects
      can be distinguished easily and clearly by evaluating the changes in both
      kinesiological and electrophysiological findings and the decreasing threshold in
      the alpha motor neuron pool. Significance: This study shows that such combined
      methods, which allow the evaluation of the alpha motor neuron pool, as well as
      kinesiological and electrophysiological parameters, are tools that cannot be
      overlooked in understanding spasticity.

PMID- 30215025
TI  - Electrodiagnosis-based management of patients with radiculopathy: The concept and
      application involving a patient with a large lumbosacral disc herniation.
AB  - Objectives: The evaluation of patients with lower back pain (LBP) is based mainly
      on clinical examinations and imaging procedures that are subjective or anatomic
      in nature. The treatments, either physical therapy or osteopathy, lack evidence
      based protocol and may be disruptive to the spine. Therefore, a neurophysiologic
      based approach to managing such patients is necessary. Methods: A 40-year-old
      female complained of LBP and radiculopathy for more than 12 years, a condition
      that was accompanied by numbness, tingling and weakness in the left leg. This
      study examined the effectiveness of using an innovative concept and method on a
      patient with a 19-mm disc herniation. An electro diagnosis-based evaluation and
      treatment approach testing tool, Soleus H-reflexes, was applied during unloading
      (with the patient lying down), loading (with the patient standing or sitting),
      and various trunk position protocols. A structured treatment was based on the
      results of H-reflex, including direction-sensitive exercises and manipulation,
      progressing from unloading to full loading. A custom-based home program was
      developed for sleeping and sitting positions, with all being directed at non
      invasively decompressing the compromised nerve root. Data was analyzed using
      descriptive statistics. Intervention and results: Stepwise application of the
      developed procedures resulted in complete resolution of the radicular and spinal
      symptoms, with a reduction in the size of the herniated disc from 19 mm to 4 mm
      and recovery of the H-amplitude by the end of the treatment. Functional recovery
      was also complete by the end of the program. A follow-up after 12 months showed
      maintained results. Conclusions: The discussed concept and method exhibited their
      effectiveness in this case study, and the results obtained are due to the
      consistency and maintenance of the neural decompression using a direction
      sensitive therapy protocol. Significance: Direction sensitive exercise therapy
      based on H-reflex testing is effective in treating large herniated lumbar discs.

PMID- 30215024
TI  - Method-of-limits; Cold and warm perception thresholds at proximal and distal body
      regions.
AB  - Objective: Thermal quantitative sensory testing with the 'Method-of-Limits' is an
      established rationale for detection of small nerve fiber dysfunction, but
      adequate reference values are crucial for such evaluations, regardless of the
      underlying cause. This study assessed reference data for cold- (CPT) and warm-
      (WPT) perception thresholds at both proximal and distal sites in eight body
      regions of the lower and upper extremities, all determined within the same test
      session for each subject. Methods: Seventy-five healthy subjects (aged 16-72
      years) were tested according to the method-of-limit for CPT and WPT at the dorsum
      of the foot, the medial and lateral lower leg, the ventral thigh, the thenar
      eminence, the radial and ulnar part of the lower arm, and the anterior deltoid
      part of the upper arm. Results: Overall, thermal perception thresholds (TPT)
      varied with test location, but were higher in the lower than in the upper part of
      the body, also WPT were generally higher than CPT. TPT at the dorsum foot highly
      correlated with age, while inconsistent correlations were noted between TPT and
      age or height at other tested locations. Conclusion: This study describes for the
      first time reference values at eight defined body regions, at both proximal and
      distal sites. Significance: The report enables refined evaluations of general
      small nerve fiber function, as assessed by quantitative thermal sensory testing
      with the Method-of-Limits.

PMID- 30215026
TI  - Stimulated single-fiber electromyography (sSFEMG) in Lambert-Eaton syndrome.
AB  - Objective: To report the clinical features and the neurophysiological approach of
      a patient with Lambert-Eaton myasthenic syndrome (LEMS), highlighting the
      diagnostic role of the stimulated single fiber electromyography (sSFEMG). Case
      report: A 60-year-old woman presenting with the LEMS triad (proximal and axial
      weakness, autonomic dysfunction and areflexia) was evaluated by
      neurophysiological tests (electroneuromyography, repetitive stimulation test
      (TSR), voluntary and stimulated SFEMG). We reported: 1) increase of compound
      muscle action potential (CMAP) amplitude (>60%) following brief isometric
      exercise compared to the rest (baseline); 2) decremental/incremental response of
      CMAP amplitude at low- (3 Hz) and high-frequency (30 Hz) repetitive stimulation
      test (RST), respectively; 3) increased neuromuscular jitter and blocking at
      voluntary single-fiber electromyography (vSFEMG); 4) stimulation rate-dependent
      reduction of the neuromuscular jitter and blocking at sSFEMG. Diagnosis was
      confirmed by serological demonstration of circulating voltage gated calcium
      channels (VGCC) antibodies. Significance: The present case highlights the role of
      the sSFEMG in the diagnosis of LEMS, underling the stimulation rate-dependency of
      both neuromuscular jitter and blocks.

PMID- 30215027
TI  - Image Registration for Microwave Tomography of the Breast Using Priors From
      Nonsimultaneous Previous Magnetic Resonance Images.
AB  - Microwave imaging is a low-cost imaging method that has shown promise for breast
      imaging and, in particular, neoadjuvant chemotherapy monitoring. The early
      studies of microwave imaging in the therapy monitoring setting are encouraging.
      For the neoadjuvant therapy application, it would be desirable to achieve the
      most accurate possible characterization of the tissue properties. One method to
      achieve increased resolution and specificity in microwave imaging reconstruction
      is the use of a soft prior regularization. The objective of this study is to
      develop a method to use magnetic resonance (MR) images, taken in a different
      imaging configuration, as this soft prior. To enable the use of the MR images as
      a soft prior, it is necessary to register the MR images to the microwave imaging
      space. Registration fiducials were placed around the breast that are visible in
      both the MRI and with an optical scanner integrated into the microwave system.
      Utilizing these common registration locations, numerical algorithms have been
      developed to warp the original breast MR images into a geometry closely
      resembling that in which the breast is pendant in the microwave system.

PMID- 30215029
TI  - Editorial: New Trends in Connectomics.
AB  - Connectomics is an integral part of network neuroscience. The field has undergone
      rapid expansion over recent years and increasingly involves a blend of
      experimental and computational approaches to brain connectivity. This Focus
      Feature on "New Trends in Connectomics" aims to track the progress of the field
      and its many applications across different neurobiological systems and species.

PMID- 30215028
TI  - Multi-Tracer Guided PET Image Reconstruction.
AB  - Multi-tracer positron emission tomography (PET) has the potential to enhance PET
      imaging by providing complementary information from different physiological
      processes. However, one or more of the images may present high levels of noise.
      Guided image reconstruction methods transfer information from a guide image into
      the PET image reconstruction to encourage edge-preserving noise reduction. In
      this work we aim to reduce noise in poorer quality PET datasets via guidance from
      higher quality ones by using a weighted quadratic penalty approach. In
      particular, we applied this methodology to [18F]fluorodeoxyglucose (FDG) and
      [11C]methionine imaging of gliomas. 3D simulation studies showed that guiding the
      reconstruction of methionine datasets using pre-existing FDG images reduced
      reconstruction errors across the whole-brain (-8%) and within a tumour (-36%)
      compared to maximum likelihood expectation-maximisation (MLEM). Furthermore,
      guided reconstruction outperformed a comparable non-local means filter,
      indicating that regularising during reconstruction is preferable to post
      reconstruction approaches. Hyperparameters selected from the 3D simulation study
      were applied to real data, where it was observed that the proposed FDG-guided
      methionine reconstruction allows for better edge preservation and noise reduction
      than standard MLEM. Overall, the results in this work demonstrate that
      transferring information between datasets in multi-tracer PET studies improves
      image quality and quantification performance.

PMID- 30215030
TI  - The network architecture of value learning.
AB  - Value guides behavior. With knowledge of stimulus values and action consequences,
      behaviors that maximize expected reward can be selected. Prior work has
      identified several brain structures critical for representing both stimuli and
      their values. Yet, it remains unclear how these structures interact with one
      another and with other regions of the brain to support the dynamic acquisition of
      value-related knowledge. Here, we use a network neuroscience approach to examine
      how BOLD functional networks change as 20 healthy human subjects learn the values
      of novel visual stimuli over the course of four consecutive days. We show that
      connections between regions of the visual, frontal, and cingulate cortices become
      stronger as learning progresses, with some of these changes being specific to the
      type of feedback received during learning. These results demonstrate that
      functional networks dynamically track behavioral improvement in value judgments,
      and that interactions between network communities form predictive biomarkers of
      learning.

PMID- 30215031
TI  - Putting the "dynamic" back into dynamic functional connectivity.
AB  - The study of fluctuations in time-resolved functional connectivity is a topic of
      substantial current interest. As the term "dynamic functional connectivity"
      implies, such fluctuations are believed to arise from dynamics in the neuronal
      systems generating these signals. While considerable activity currently attends
      to methodological and statistical issues regarding dynamic functional
      connectivity, less attention has been paid toward its candidate causes. Here, we
      review candidate scenarios for dynamic (functional) connectivity that arise in
      dynamical systems with two or more subsystems; generalized synchronization,
      itinerancy (a form of metastability), and multistability. Each of these scenarios
      arises under different configurations of local dynamics and intersystem coupling:
      We show how they generate time series data with nonlinear and/or nonstationary
      multivariate statistics. The key issue is that time series generated by coupled
      nonlinear systems contain a richer temporal structure than matched multivariate
      (linear) stochastic processes. In turn, this temporal structure yields many of
      the phenomena proposed as important to large-scale communication and computation
      in the brain, such as phase-amplitude coupling, complexity, and flexibility. The
      code for simulating these dynamics is available in a freeware software platform,
      the Brain Dynamics Toolbox.

PMID- 30215032
TI  - Heritability of the human connectome: A connectotyping study.
AB  - Recent progress in resting-state neuroimaging demonstrates that the brain
      exhibits highly individualized patterns of functional connectivity-a
      "connectotype." How these individualized patterns may be constrained by
      environment and genetics is unknown. Here we ask whether the connectotype is
      familial and heritable. Using a novel approach to estimate familiality via a
      machine-learning framework, we analyzed resting-state fMRI scans from two well
      characterized samples of child and adult siblings. First we show that individual
      connectotypes were reliably identified even several years after the initial
      scanning timepoint. Familial relationships between participants, such as siblings
      versus those who are unrelated, were also accurately characterized. The
      connectotype demonstrated substantial heritability driven by high-order systems
      including the fronto-parietal, dorsal attention, ventral attention, cingulo
      opercular, and default systems. This work suggests that shared genetics and
      environment contribute toward producing complex, individualized patterns of
      distributed brain activity, rather than constraining local aspects of function.
      These insights offer new strategies for characterizing individual aberrations in
      brain function and evaluating heritability of brain networks.

PMID- 30215033
TI  - ADHD and attentional control: Impaired segregation of task positive and task
      negative brain networks.
AB  - In children with attention deficit hyperactivity disorder (ADHD) difficulty
      maintaining task focus may relate to the coordinated, negatively correlated
      activity between brain networks that support the initiation and maintenance of
      task sets (task positive networks) and networks that mediate internally directed
      processes (i.e., the default mode network). Here, resting-state functional
      connectivity MRI between these networks was examined in ADHD, across development,
      and in relation to attention. Children with ADHD had reduced negative
      connectivity between task positive and task negative networks (p = 0.002).
      Connectivity continues to become more negative between these networks throughout
      development (7-15 years of age) in children with ADHD (p = 0.005). Regardless of
      group status, females had increased negative connectivity (p = 0.003). In regards
      to attentional performance, the ADHD group had poorer signal detection (d') on
      the continuous performance task (CPT) (p < 0.0001), more so on easy than
      difficult d' trials (p < 0.0001). The reduced negative connectivity in children
      with ADHD also relates to their attention, where increased negative connectivity
      is related to better performance on the d' measure of the CPT (p = 0.008). These
      results highlight and further strengthen prior reports underscoring the role of
      segregated system integrity in ADHD.

PMID- 30215034
TI  - Using network analysis to localize the epileptogenic zone from invasive EEG
      recordings in intractable focal epilepsy.
AB  - Treatment of medically intractable focal epilepsy (MIFE) by surgical resection of
      the epileptogenic zone (EZ) is often effective provided the EZ can be reliably
      identified. Even with the use of invasive recordings, the clinical
      differentiation between the EZ and normal brain areas can be quite challenging,
      mainly in patients without MRI detectable lesions. Consequently, despite
      relatively large brain regions being removed, surgical success rates barely reach
      60-65%. Such variable and unfavorable outcomes associated with high morbidity
      rates are often caused by imprecise and/or inaccurate EZ localization. We
      developed a localization algorithm that uses network-based data analytics to
      process invasive EEG recordings. This network algorithm analyzes the centrality
      signatures of every contact electrode within the recording network and
      characterizes contacts into susceptible EZ based on the centrality trends over
      time. The algorithm was tested in a retrospective study that included 42 patients
      from four epilepsy centers. Our algorithm had higher agreement with EZ regions
      identified by clinicians for patients with successful surgical outcomes and less
      agreement for patients with failed outcomes. These findings suggest that network
      analytics and a network systems perspective of epilepsy may be useful in
      assisting clinicians in more accurately localizing the EZ.

PMID- 30215036
TI  - Low-dimensional morphospace of topological motifs in human fMRI brain networks.
AB  - We present a low-dimensional morphospace of fMRI brain networks, where axes are
      defined in a data-driven manner based on the network motifs. The morphospace
      allows us to identify the key variations in healthy fMRI networks in terms of
      their underlying motifs, and we observe that two principal components (PCs) can
      account for 97% of the motif variability. The first PC of the motif distribution
      is correlated with efficiency and inversely correlated with transitivity. Hence
      this axis approximately conforms to the well-known economical small-world trade
      off between integration and segregation in brain networks. Finally, we show that
      the economical clustering generative model proposed by Vertes et al. (2012) can
      approximately reproduce the motif morphospace of the real fMRI brain networks, in
      contrast to other generative models. Overall, the motif morphospace provides a
      powerful way to visualize the relationships between network properties and to
      investigate generative or constraining factors in the formation of complex human
      brain functional networks.

PMID- 30215037
TI  - Clinicopathologic Features of Non-Small-Cell Lung Cancer Harboring an NTRK Gene
      Fusion.
AB  - Purpose: Gene rearrangements involving NTRK1/2/3 can generate fusion oncoproteins
      containing the kinase domains of TRKA/B/C, respectively. These fusions are rare
      in non-small cell lung cancer (NSCLC), with frequency previously estimated to be
      <1%. Inhibition of TRK signaling has led to dramatic responses across tumor types
      with NTRK fusions. Despite the potential benefit of identifying these fusions,
      the clinicopathologic features of NTRK fusion-positive NSCLCs are not well
      characterized. Methods: We compiled a database of NSCLC cases harboring NTRK
      fusions. We characterized the clinical, molecular, and histologic features of
      these cases with central review of histology. Results: We identified 11 NSCLC
      cases harboring NTRK gene fusions verified by next-generation sequencing (NGS)
      and with available clinical and pathologic data, forming the study cohort.
      Fusions involved NTRK1 (7 cases) and NTRK3 (4 cases), with 5 and 2 distinct
      fusion partners, respectively. Cohort patients were 55% male, with a median age
      at diagnosis of 47.6 years (range 25.3-86.0) and a median pack year history of 0
      (range 0-58). 73% of patients had metastatic disease at diagnosis. No concurrent
      alterations in KRAS, EGFR, ALK, ROS1, or other known oncogenic drivers were
      identified. Nine cases were adenocarcinoma, including 2 invasive mucinous
      adenocarcinomas and 1 adenocarcinoma with neuroendocrine features; one was
      squamous cell carcinoma; and one was neuroendocrine carcinoma. By collating data
      on 4872 consecutively screened NSCLC cases from unique patients, we estimate a
      frequency of NTRK fusions in NSCLC of 0.23% (95% CI 0.11-0.40). Conclusion: NTRK
      fusions occur in NSCLCs across genders, ages, smoking histories, and histologies.
      Given the potent clinical activity of TRK inhibitors, we advocate that all NSCLCs
      be screened for NTRK fusions using a multiplexed NGS-based fusion assay.

PMID- 30215035
TI  - Functional and structural connectome properties in the 5XFAD transgenic mouse
      model of Alzheimer's disease.
AB  - Neurodegeneration in Alzheimer's disease (AD) is associated with amyloid-beta
      peptide accumulation into insoluble amyloid plaques. The five-familial AD (5XFAD)
      transgenic mouse model exhibits accelerated amyloid-beta deposition, neuronal
      dysfunction, and cognitive impairment. We aimed to determine whether connectome
      properties of these mice parallel those observed in patients with AD. We obtained
      diffusion tensor imaging and resting-state functional magnetic resonance imaging
      data for four transgenic and four nontransgenic male mice. We constructed both
      structural and functional connectomes and measured their topological properties
      by applying graph theoretical analysis. We compared connectome properties between
      groups using both binarized and weighted networks. Transgenic mice showed higher
      characteristic path length in weighted structural connectomes and functional
      connectomes at minimum density. Normalized clustering and modularity were lower
      in transgenic mice across the upper densities of the structural connectome.
      Transgenic mice also showed lower small-worldness index in higher structural
      connectome densities and in weighted structural networks. Hyper-correlation of
      structural and functional connectivity was observed in transgenic mice compared
      with nontransgenic controls. These preliminary findings suggest that 5XFAD mouse
      connectomes may provide useful models for investigating the molecular mechanisms
      of AD pathogenesis and testing the effectiveness of potential treatments.

PMID- 30215038
TI  - Associations of mobile source air pollution during the first year of life with
      childhood pneumonia, bronchiolitis, and otitis media.
AB  - Background: Exposure to pollution from motor vehicles in early life may increase
      susceptibility to common pediatric infections. Methods: We estimated associations
      between residential exposure to primary fine particulate matter (PM2.5), nitrogen
      oxides (NOx), and carbon monoxide (CO) from traffic during the first year of life
      and incident pneumonia, bronchiolitis, and otitis media events by age two years
      in 22,441 children from the Kaiser Air Pollution and Pediatric Asthma Study, a
      retrospective birth cohort of children born during 2000-2010 and insured by
      Kaiser Permanente Georgia. Time to first clinical diagnosis of each outcome was
      defined using medical records. Exposure to traffic pollutants was based on
      observation-calibrated estimates from A Research LINE-source dispersion model for
      near surface releases (RLINE) and child residential histories. Associations were
      modeled using Cox proportional hazards models, with exposure as a continuous
      linear variable, a natural-log transformed continuous variable, and categorized
      by quintiles. Results: During follow-up 2,181 children were diagnosed with
      pneumonia, 5,533 with bronchiolitis, and 14,373 with otitis media. We observed
      positive associations between early-life traffic exposures and all three
      outcomes; confidence intervals were widest for pneumonia as it was the least
      common outcome. For example, adjusted hazard ratios for a 1-unit increase in NOx
      on the natural log scale (a 2.7-fold increase) were 1.19 (95% CI 1.12, 1.27) for
      bronchiolitis, 1.17 (1.12, 1.22) for otitis media, and 1.08 (0.97, 1.20) for
      pneumonia. Conclusions: Our results provide evidence for modest, positive
      associations between exposure to traffic emissions and common pediatric
      infections during early childhood.

PMID- 30215039
TI  - Synergistic effect of metformin on sorafenib in in vitro study using
      hepatocellular carcinoma cell lines.
AB  - Backgrounds/Aims: Hepatocellular carcinoma (HCC) recurrence remains a great
      concern following hepatic resection and liver transplantation. We investigated
      the metformin-induced cytotoxic effects on sorafenib in an in vitro study using
      HCC cell lines. Methods: This research was conducted through an in vitro study
      using one HepG2.2.15 liver tumor and two patient-derived graft HCC cell lines.
      Results: An in vitro study revealed noticeable cytotoxic effects of metformin as
      well as noticeable synergistic cytotoxic effects of metformin and sorafenib on
      cell viability. Assays for the mechanisms of action of antitumor effects revealed
      that alpha-fetoprotein expression was suppressed by both metformin and sorafenib,
      but no synergistic effect was observed. LC3-I and LC3-II assays revealed the
      synergistic upregulation of autophagy and assays for IL-1beta, IL-6, p53, and TNF
      alpha revealed the synergistic upregulation of cell damage and apoptosis. In
      contrast, metformin did not affect HBx expression, thus no noticeable synergistic
      effect was considered to be present. Conclusions: Our in vitro study demonstrated
      cytotoxic effects of metformin and synergistic antitumor effects of sorafenib.
      These results should be verified in further clinical studies with patients of
      advanced HCC.

PMID- 30215040
TI  - Predictors of post-hepatectomy liver failure in patients undergoing extensive
      liver resections for hepatocellular carcinoma.
AB  - Backgrounds/Aims: To determine the prevalence of post-hepatectomy liver
      failure/insufficiency (PHLF/I) in patients undergoing extensive hepatic
      resections for hepatocellular carcinoma (HCC) and to assess the predictive value
      of preoperative factors for post-hepatectomy liver failure or insufficiency
      (PHLF/I). Methods: A retrospective review of patients who underwent liver
      resections for HCC between 2001 and 2013 was conducted. Preoperative parameters
      were assessed and analyzed for their predictive value of PHLF/I. Definitions used
      included the 50-50, International Study Group of Liver Surgery (ISGLS) and
      Memorial Sloan Kettering Cancer Centre (MSKCC) criteria. Results: Among the 848
      patients who underwent liver resections for HCC between 2001 and 2013, 157
      underwent right hepatectomy (RH) and extended right hepatectomy (ERH). The
      prevalence of PHLF/I was 7%, 41% and 28% based on the 50-50, ISGLS and MSKCC
      criteria, respectively. There were no significant differences in PHLF/I between
      RH and ERH. Model for End-Stage Liver Disease (MELD) score and bilirubin were the
      strongest independent predictors of PHLF/I based on the 50-50 and ISGLS/MSKCC
      criteria, respectively. Predictive models were developed for each of the criteria
      with multiple logistic regression. Conclusions: MELD score, bilirubin, alpha
      fetoprotein and platelet count showed significant predictive value for PHLF/I
      (all p<0.05). A composite score based on these factors serves as guideline for
      physicians to better select patients undergoing extensive resections to minimize
      PHLF.

PMID- 30215041
TI  - Identifying the role of neutrophil-to-lymphocyte ratio and platelets-to
      lymphocyte ratio as prognostic markers in patients undergoing resection of
      pancreatic ductal adenocarcinoma.
AB  - Backgrounds/Aims: It is important to point out that the identification of
      inflammation is an essential component of the pathogenesis and the progression of
      cancer. In this study, we analysed the neutrophil-to-lymphocyte ratio (NLR) and
      the platelets-to-lymphocyte ratio (PLR), with an overall survival (OS) in
      patients with pancreatic ductal adenocarcinoma (PDAC), who were treated with a
      resection following or not following a procedure of neoadjuvant
      chemotherapy/chemoradiation. We intended to identify the significance of the role
      of NLR and PLR, as prognostic markers in patients undergoing surgery for PDAC.
      Methods: There were 127 patients enrolled in the study. The NLR and PLR were
      calculated on the basis of the pre-treatment blood cell count. An NLR>4 and a PLR
      >120 were considered to be elevated as measured. OS was analysed in relation to
      the NLR and PLR values, by using both the Kaplan-Meier and multivariate Cox
      regression methods. Results: Both high the NLR and high PLR were associated with
      a decreased OS in the univariate analysis. In the multivariate analysis, the high
      NLR, but not the high PLR, was an independent predictor of a decreased OS. When
      we divided patients into three groups (group 1: normal both NLR and PLR, group 2:
      high NLR or high PLR, group 3: high both NLR and PLR), the three-years OS rates
      for these groups were 48%, 32%, 7% (p=0.001) respectively. Conclusions: It is
      noted that the pre-treatment NLR is an independent adverse prognostic factor, and
      considered to be superior to the PLR, in patients who undergo a resection for
      PDAC following or not neoadjuvant chemotherapy/chemoradiation.

PMID- 30215042
TI  - Surgical approaches to hepatic hydatidosis ranging from partial cystectomy to
      liver transplantation.
AB  - Backgrounds/Aims: A wide range of surgical approaches has been described for
      hepatic hydatidosis aiming primarily at the reduction of disease recurrence and
      minimization of postoperative morbidity. Methods: A database analysis of patients
      with liver hydatidosis who underwent different surgical procedures between March
      2010 and May 2016 was performed. Results: A total of 21 patients with cystic
      echinococcosis (CE) and four cases of alveolar echinococcosis (AED) were
      detected. Nine patients manifested recurrent disease at presentation. Among CE
      cases, 5 underwent partial cystectomy (2 laparoscopic and 3 open), 9 cysto
      pericystectomy (7 open and 2 robotic) and 7 hepatectomies (1 central, 4 right, 1
      left and 1 right trisectionectomy). Living donor liver transplantation was
      performed in 3 patients with AED and the fourth patient underwent right
      trisectionectomy with en bloc resection of hepatic flexure and right diaphragm.
      Seven developed Clavien grade II and three grade III complications. The mean
      follow-up of CE was 34.19+/-19.75 months. One patient of laparoscopic partial
      cystectomy developed disease recurrence at 14 months. No recurrence was detected
      at a mean follow-up of 34+/-4.58 months following LDLT and at 24 months following
      multivisceral resection for AED. Conclusions: The whole spectrum of tailored
      surgical approaches ranging from minimally invasive to open and extended liver
      resections represents safe, effective and recurrence-free treatment of hepatic
      hydatidosis.

PMID- 30215043
TI  - A retrospective review of correlative radiological assessment and surgical
      exploration for hilar cholangiocarcinoma.
AB  - Backgrounds/Aims: Hilar cholangiocarcinomas (HCCAs) are tumors that involve the
      biliary confluence; at present, radical surgery offers the only chance of long
      term survival, but this can be challenging given the complexity of the hilar
      anatomy. Blumgart and Jarnagin described a preoperative staging system that
      incorporates the effect of local tumor extent and its impact on adjacent
      structures and that has been demonstrated to correlate better with actual
      surgical resectability. The primary aim of this study is to describe the
      correlation between preoperative Blumgart-Jarnagin staging and its correlation
      with surgical resectability. Methods: Patients who underwent surgical resection
      for hilar cholangiocarcinoma at Singapore General Hospital between January 1,
      2002, and January 1, 2013, were identified from a prospectively maintained
      institutional database. All patients were staged based on the criteria described
      by Blumgart and Jarnagin. Correlation with surgical resectability was then
      determined. Results: A total of 19 patients were identified. Overall
      resectability was 57.8% (n=11). Patients with Blumgart-Jarnagin stage T1 had the
      highest rates of resectability at 80%; patients with stage T2 and T3 disease had
      resectability rates of 25% and 40% respectively. Median overall survival was 13.6
      months. Conclusions: The Blumgart-Jarnagin staging system is useful for
      predicting tumor resectability in HCCA.

PMID- 30215044
TI  - Outcomes of liver resection in patients with colorectal liver metastases by
      laparoscopic or open surgery.
AB  - Backgrounds/Aims: Colorectal cancer is found with liver metastases about 20-25%
      due to characteristics of cancer itself. Approximately 20% of liver metastases
      are found to be resectable. The objective of this study was to evaluate short
      term outcomes of patients who received liver resection with colorectal cancer
      operation in our center by laparoscopic surgery or open surgery. Methods: Short
      term outcomes of laparoscopic surgery of liver resection (LSLR) group who
      underwent liver resection for colorectal liver metastases (CRLM) at a single
      institute from 2013 to 2016 were compared to those of open surgery of liver
      resection (OSLR) group. Results: A total of 123 patients underwent liver
      resection for CRLM, including 101 (82.1%) patients in the OSLR group and 22
      (17.9%) patients in the LSLR group. There were significant differences in tumor
      characteristics between the two groups, including synchronous and metachronous
      (p=0.004), tumor number (p<0.001), and tumor margin (p=0.002). For postoperative
      outcomes, only the length of hospital stay (LOS) was significantly different
      between the two groups (8.5 days in LSLR vs. 11 days in OSLR, p<0.001). There was
      no significant difference in overall rate of postoperative complications between
      the two groups (9.1% in LSLR vs. 23.8% in OSLR, p=0.158). Conclusions: There are
      no significant differences in postoperative outcomes between LSLR and OSLR except
      LOS, liver metastasis number, and resection margin. LSLR may be favorable for
      highly selected patients with CRLM.

PMID- 30215046
TI  - How to prevent the postoperative pancreatic fistula with an ethylene vinyl
      alcohol copolymer (Onyx(r)): A proposal of a new technique.
AB  - Backgrounds/Aims: Despite the advances in identifying risk factors, improving
      operative technique, and postoperative patient care, pancreatic leakage after
      pancreatic resection remains a highly debated topic. The aim of this study is to
      describe our technique and our initial experience with the intraoperative
      embolization of the main pancreatic duct with an Ethylene Vinyl Alcohol Copolymer
      (Onyx(r)). Methods: Two patients of 63 and 64 years underwent
      pancreaticoduodenectomy for a cholangiocarcinoma of the extrahepatic bile duct
      and a pancreatic adenocarcinoma, respectively. At the time of pancreatic
      parenchyma resection, a Wirsung duct was identified and catheterized. A
      wirsungography was done and then, embolization with Onyx(r) was carried out under
      fluoroscopic control. Results: Neither of the patients developed a postoperative
      pancreatic fistula. They were discharged to home on the 17th and 18th
      postoperative day, respectively. At the last follow-up, no recurrence was found.
      The two patients became diabetics; both needed the support of supplementary
      pancreatic enzymes. Conclusions: To our knowledge, we are the first to describe
      this technique, which seems safe and reliable. Studies on this subject with more
      patients are needed to confirm the validity of this procedure.

PMID- 30215045
TI  - Role of prophylactic antibiotics in elective laparoscopic cholecystectomy: A
      systematic review and meta-analysis.
AB  - Backgrounds/Aims: The role of prophylactic antibiotics for laparoscopic
      cholecystectomy in low-risk patients is still unclear. This study aimed to verify
      the conclusion of previous meta-analyses concerning the effectiveness of
      antibiotic prophylaxis for elective laparoscopic cholecystectomy in low-risk
      patients. Methods: Comprehensive literature searches were performed on electric
      databases and manual searches. Randomized controlled trials (RCTs), prospective
      studies, and retrospective studies comparing antibiotic prophylaxis to placebo or
      no antibiotics in low-risk elective laparoscopic cholecystectomy were included.
      Results: This study included 28 RCTs, three prospective studies, and three
      retrospective studies. In RCTs, prophylactic antibiotics did not prevent deep
      surgical site infections (SSI) (RR 1.10, 95% confidence interval [CI] [0.45
      2.69], p=0.84) but reduced SSI (RR 0.70, 95% CI [0.53-0.94], p=0.02), and
      superficial SSI (RR 0.58, 95% CI [0.42-0.82], p=0.01). Prospective studies showed
      prophylactic antibiotics did not reduce superficial SSI (RR 0.35, 95% CI [0.01
      8.40], p=0.52) but reduced SSI (RR 0.12, 95% CI [0.04-0.35], p=0.0001). In
      retrospective studies, antibiotic prophylaxis did not reduce SSI (RR 1.59, 95% CI
      [0.30-8.32], p=0.58). The pooled data (12121 patients) including RCTs and
      prospective and retrospective studies showed that prophylactic antibiotics were
      not effective in preventing deep SSI (RR 1.01 95% CI [0.46-2.21], p=0.98) but
      effective in reducing SSI (RR 0.67, 95% CI [0.51-0.88], p=0.003) and superficial
      SSI (RR 0.61, 95% CI [0.45-0.83], p=0.002). Conclusions: The use of prophylactic
      antibiotics is effective for reducing the incidence of SSI and superficial SSI
      but is not effective for preventing deep SSI in low-risk patients who underwent
      elective laparoscopic cholecystectomy.

PMID- 30215047
TI  - Comparison of Blumgart versus conventional duct-to-mucosa anastomosis for
      pancreaticojejunostomy after pancreaticoduodenectomy.
AB  - Backgrounds/Aims: Pancreatic leakage is a major cause of postoperative death and
      morbidity after pancreaticoduodenectomy (PD). A recent study introduced Blumgart
      anastomosis (BA), which minimizes severe complications after PD. This study
      compares BA with conventional anastomosis (CA) for pancreaticojejunostomy (PJ)
      after PD at a single institution. Methods: A total of 87 patients who underwent
      PD at our hospital between January 2003 and October 2015 were enrolled in this
      study. The patients were divided into two groups according to the anastomosis
      type. Of them, 44 patients underwent anastomosis using CA (group A, conventional
      duct-to-mucosa anastomosis) and 43 underwent anastomosis using BA (group B,
      Blumgart anastomosis). Results: There was a significant difference in duration of
      the operation between groups A and B (473.1+/-102.0 versus 386.4+/-58.5 min,
      p<0.001) and intraoperative transfusion (2.2+/-2.7 versus 0.7+/-1.5 units,
      p<0.001). There was no significant difference between groups A and B in incidence
      of postoperative pancreatic fistula (POPF) (43.2% versus 27.9%, p=0.137)
      ,postoperative hemorrhage (PPH) (13.7% versus 7.0%, p=0.209), delayed gastric
      emptying (DGE) (29.5% versus 9.3%, p=0.063), surgical and non-surgical
      complications (60.5% versus 59.1%, p=0.896), length of ICU stay (9.0+/-6.3 versus
      7.4+/-7.2 days, p=0.099), or length of postoperative hospital stay (37.7+/-16.7
      versus 41.6+/-15.1 days, p=0.118). Conclusions: The results of this study suggest
      that BA-type PJ is not inferior to CA-type PJ in terms of postoperative
      complications.

PMID- 30215048
TI  - Vein resection in patients with adenocarcinoma of the head of pancreas adherent
      to the portomesenteric venous axis is beneficial despite a high rate of R1
      resection.
AB  - Backgrounds/Aims: En-bloc vein resection (VR) for pancreatic ductal
      adenocarcinoma (PDAC) of the head of pancreas adherent to the portomesenteric
      axis benefits patients when the vein wall is not infiltrated by tumour and an R0
      resection is achieved, albeit at the expense of greater morbidity and mortality.
      Methods: A retrospective review of pancreaticoduodenectomy for PDAC over 6 years
      was conducted. Patients were divided into a standard resection group (Group SR)
      and simultaneous vein resection group (Group VR) and compared for outcome.
      Results: The study group consisted of 41 patients (Group SR 15, Group VR 26). VR
      was performed by end-to-end reconstruction in 12 patients and with interposition
      grafts in 13 cases (autologous vein in 10, PTFE in 3). R1 resections occurred in
      49% patients, with the superior mesenteric artery margin most commonly involved.
      Patients with Ishikawa grade III and IV vein involvement were more likely to
      carry a positive SMA margin (p=0.04). Involvement of the splenoportal junction
      was associated with a significantly greater risk of pancreatic transection margin
      involvement. No difference in morbidity was seen between the groups. Median
      survival in the entire group of patients was 17 months and did not vary
      significantly between the groups. The only significant predictor of survival was
      lymph node status. Conclusions: Venous involvement by proximal PDAC is indicative
      of tumor location rather than tumor biology. VR improves outcomes in patients
      with tumor adhesion to the portomesenteric venous axis despite a high incidence
      of R1 resections and greater operative mortality.

PMID- 30215049
TI  - Undifferentiated embryonal sarcoma of the liver in adult patient: A report of two
      cases.
AB  - Primary sarcomas of the liver are unusual neoplasms developing in adults. They
      constitute a heterogeneous group of neoplasms including undifferentiated
      embryonal sarcoma. Patients usually present with an abdominal mass and abdominal
      pain. Case 1: A 53-year-old woman presented with abdominal pain. Computed
      tomography showed an occupying mass in the right lobule and an intra-auricular
      multi-lobulated mass suggestive of a secondary deposit. Biopsy of the hepatic
      lesion revealed undifferentiated embryonal sarcoma. Despite radiotherapy and
      supportive measures, her overall status progressively worsened until cardiac
      arrest. Case 2: A 41-year-old woman presented with hepatomegaly. Abdominal
      imaging showed cystic lesions in the right hepatic lobule with multiple septae.
      The patient underwent extended right hepatectomy and a histopathological study
      reported high-grade undifferentiated embryonal sarcoma. Two years after surgery,
      a new cystic lesion in the surgical site was recorded and chemotherapy was
      scheduled. The lesion remained stable for three years when disease progression
      was observed and second-line chemotherapy was initiated. Although
      undifferentiated embryonal sarcoma of the liver has poor prognosis, early
      diagnosis is essential to increase the chances of survival. Currently, surgical
      resection and chemotherapy are the primary treatment modalities.

PMID- 30215050
TI  - Long-term complete response after transcatheter arterial chemoembolization and
      stereotactic body radiation therapy in a patient with hepatocellular carcinoma at
      the caudate lobe.
AB  - It is expected that a combination of transcatheter arterial chemoembolization
      (TACE) with stereotactic body radiation therapy (SBRT) may induce synergistic
      therapeutic effects in hepatocellular carcinoma (HCC), which would result in a
      high rate of complete therapeutic response. In this study, we present the 5-year
      clinical course of a patient who had HCC at the caudate lobe, which was treated
      with TACE and SBRT. A 53-year-old male was diagnosed with an 8 cm-sized HCC at
      the caudate lobe with compression of the inferior vena cava (IVC). For fear of
      pulmonary metastasis, we decided to perform sequential TACE-radiotherapy instead
      of upfront hepatectomy, although the tumor appeared resectable. The first session
      of TACE, SBRT with 12 fractions, and the second session of TACE were sequentially
      performed. The patient was administered metformin for chemoprevention. Over the
      course of a 5-year follow-up, there was no evidence of HCC recurrence. We
      reported the clinical sequence of a patient showing complete therapeutic response
      of HCC at the caudate lobe after a combination of TACE and radiotherapy. This
      type of combined locoregional treatment can be a therapeutic option for HCC at
      the caudate lobe with marginal resectability.

PMID- 30215051
TI  - Percutaneous transhepatic biliary drainage catheter fracture: A case report.
AB  - Percutaneous transhepatic biliary drainage (PTBD) is safe treatment for biliary
      decompression given certain indications. However, this is temporary until
      definitive drainage is established. We report on a 76-year-old lady with
      recurrent pyogenic cholangitis and PTBD catheter fracture. She had hepatitis B
      virus-related Child-Pugh class A liver cirrhosis, hypothyroidism,
      hyperlipidaemia, and previous atrial fibrillation with a background of mild
      mitral, tricuspid and aortic valvular regurgitation. She had history of
      laparoscopic cholecystectomy in the past. She was deemed to be a high operative
      risk and declined hepatic resection. She had undergone multiple endoscopic and
      percutaneous biliary interventions to control sepsis and stone burden. A
      bilateral PTBD catheter was left in situ with plans for 3-monthly change.
      However, she defaulted follow-up and presented 11 months later with complaints of
      pain over the drain site and inability to flush the right catheter. Abdominal X
      ray and computed tomography scans detected right catheter fracture at two places,
      making three fragments. She underwent percutaneous removal of the proximal
      fragment by an interventional radiology team. A temporary 4 Fr catheter was
      inserted to maintain biliary access. Endoscopic removal of the intra-biliary
      fragments was done the next day. Complete removal was confirmed on fluoroscopy.
      Finally, the 4 Fr catheter was replaced by a new 12 Fr catheter. The patient was
      discharged well.

PMID- 30215052
TI  - Adrenal metastasis in sequentially developed combined hepatocellular carcinoma
      cholangiocarcinoma: A case report.
AB  - The incidence of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC)
      in a single patient accounts for only 0.4 to 14% of all primary liver cancer.
      However, the prognosis of its intrahepatic cholangiocarcinoma (ICC) component is
      poor. We experienced a unique case of a sequentially developed cHCC-CC with
      adrenal metastasis as the primary presentation and a hidden primary
      hepatocellular carcinoma. A 65-year-old female with a history of jaundice and
      abdominal discomfort was diagnosed with S4 ICC measuring 5 cm in diameter, and
      characterized histologically as papillary adenocarcinoma with intraductal growth,
      but without any evidence of malignant hepatocyte. S4 segmentectomy with
      hepaticojejunostomy revealed no additional masses. A follow-up CT scan 3 months
      after surgery showed a right adrenal mass with markedly increased serum AFP (4950
      ng/mL), which was treated with right adrenalectomy. Histopathology revealed a
      metastatic hepatocellular carcinoma testing positive for AFP, glypican-3, and
      hepatocytes, but negative for CD-10, inhibin-alpha, EMA, S-100, and cytokeratin
      7. Serum AFP level immediately plummeted to 4.1 ng/mL upon adrenal mass removal.
      A recurrent S7 liver mass was suspected 1 year later with serum AFP value of 7.6
      ng/mL, and characteristic CT imaging of HCC. TACE was performed with good
      response. Adrenal metastasis may manifest as the primary focus of hepatocellular
      carcinoma in sequentially developed cHCC-CC patients with hidden primary HCC.
      cHCC-CC should be considered in the differential diagnosis of cholangiocarcinoma
      with elevated AFP.

PMID- 30215053
TI  - Gallbladder agenesis: A case report and brief review.
AB  - Agenesis of the gallbladder and cystic duct represents one of the rarest
      anomalies of the biliary system, with a reported incidence of 0.007% to 0.027%.
      Almost half of the patients develop common duct stones and 23% of them manifest
      signs and symptoms that mimic biliary colic. We present the case of a woman
      presenting with symptoms of biliary colic. Based on the clinical findings and
      after abdominal ultrasonography, which showed hyperechoic material in the
      gallbladder fossa, a laparoscopic cholecystectomy was planned. Laparoscopy failed
      to reveal either gallbladder or cystic duct. The procedure was continued to
      further search for ectopic sites of gallbladder. A condition of gallbladder
      agenesis was hypothesized and the procedure was aborted without dissection of
      hepatic pedicle or conversion to laparotomy. Agenesis of gallbladder and cystic
      duct was confirmed via pos-operative magnetic resonance cholangiopancreatography.
      We report our experience with regard to the challenges associated with the
      diagnosis and management, and a brief review of the literature of this rare
      pathology.

PMID- 30215054
TI  - Trastuzumab-mediated cardiotoxicity: current understanding, challenges, and
      frontiers.
AB  - Trastuzumab, an epidermal growth factor receptor 2 (HER2) targeting humanized
      monoclonal antibody, has been approved for the treatment HER2-positive breast
      cancer and HER2-positve metastatic gastric cancer. However, cardiotoxicity
      associated with its clinical application poses challenges for clinicians and
      patients, mechanisms of which are still evolving. This review will summarize the
      current mechanistic understanding of trastuzumab-mediated cardiotoxicity, discuss
      the novel role of DNA topoisomerase IIB as a shared target for enhanced
      cardiotoxicity induced by trastuzumab and anthracyclines-based combination
      regimens, and speculate the potential impact of trastuzumab intervention in
      immune checkpoint inhibitors-based therapies.

PMID- 30215056
TI  - Introduction to Conditioning Medicine.

PMID- 30215055
TI  - High Frequency Acceleration: A New Tool for Alveolar Bone Regeneration.
AB  - Introduction: A common problem in clinical dentistry is the significant and rapid
      bone loss that occurs after periodontitis, osteoporosis, tooth extractions, lack
      of function, or any other pathologic condition that target the alveolar bone.
      Currently there is no stable solution for the long-term preservation or
      rehabilitation of alveolar bone. In this article, we review the latest concepts
      on bone response to mechanical stimulation, and summarize the results of our
      studies on the effect of high frequency acceleration (HFA) on healthy alveolar
      bone and on healing alveolar bone after extractions. Methods: In both studies, we
      used adult Sprague Dawley rats to test the response of alveolar bone to different
      frequencies and accelerations applied to the maxillary molars. Results: Once we
      determined which parameters of HFA induced a higher osteogenic response, we
      tested the effect of this mechanical stimulation during bone healing after molar
      extraction. Our studies strongly show that HFA can stimulate bone formation in
      the healthy alveolar bone surrounding the tooth/point of application as well as
      the distant bone surrounding the neighboring teeth. When HFA was applied to the
      second molar, after extraction of the third molar, it accelerated bone healing
      and prevented alveolar bone resorption in and around the extraction socket.
      Conclusion: HFA is a noninvasive safe treatment that can be used to prevent
      alveolar bone loss, accelerate bone healing and to improve the quality and
      quantity of alveolar bone under both physiological and pathological conditions.

PMID- 30215058
TI  - Hyperbaric Oxygen Therapy for Alzheimer's Disease.
AB  - Recent studies indicate that hyperbaric oxygen therapy (HBOT), a well-established
      therapy for decompression illness, could be a potential therapy for Alzheimer's
      disease (AD). However, due to oxygen toxicity i.e., increased oxidative stress
      implicated in HBOT, the risk and benefit of HBOT for AD patients need to be
      further assessed clinically.

PMID- 30215059
TI  - Is it a Prime Time for AI-powered Virtual Drug Screening?
AB  - Drug development pipeline inefficiency has called for more novel solutions and
      cutting-edge technologies. Artificial intelligence (AI)-based methods including
      different machine- and deep-learning algorithms have been employed for virtual
      drug screening. With the continuous refinement of algorithms, improvement of
      computing hardware, and increased availability of molecular datasets for drug
      development, it is certainly a prime time for AI-powered virtual drug screening.

PMID- 30215057
TI  - Ischemic Conditioning and neonatal hypoxic ischemic encephalopathy: a literature
      review.
AB  - Hypoxic Ischemic Encephalopathy (HIE) is the result of severe anoxic brain injury
      during the neonatal period and causes life-long morbidity and premature
      mortality. Currently, therapeutic hypothermia immediately after birth is the
      standard of care for clinically relevant HIE. However, therapeutic hypothermia
      alone does not provide complete neuroprotection and there is an urgent need for
      adjunctive therapies. Ischemic conditioning is an adaptive process of endogenous
      protection in which small doses of sub-lethal ischemia can provide a protection
      against a lethal ischemic event. Remote Ischemic Post-conditioning (RIPC), a form
      of ischemic conditioning, is highly translatable for HIE diagnosed immediately
      after birth as the conditioned ischemic stimulus is applied at the limb after the
      lethal ischemic episode. A number of studies in neonatal rats have demonstrated
      that RIPC is effective at reducing injury in focal cerebral ischemia models and
      improves neurological outcomes. In this review, we focus on the available data on
      HIE and its current treatment, models in HIE studies, ischemic conditioning/RIPC
      and its mechanism. We discuss in particular the effect of RIPC on neonatal brain
      with HIE. We postulate that combining RIPC with standard therapeutic hypothermia
      can be an attractive therapeutic approach for HIE.

PMID- 30215060
TI  - SAS(r) Macros for Computing the Mediated Effect in the Pretest-Posttest Control
      Group Design.
AB  - Mediation analysis is a statistical technique for investigating the extent to
      which a mediating variable transmits the relation of an independent variable to a
      dependent variable. Because it is useful in many fields, there have been rapid
      developments in statistical mediation methods. The most cutting-edge statistical
      mediation analysis focuses on the causal interpretation of mediated effect
      estimates. Cause-and-effect inferences are particularly challenging in mediation
      analysis because of the difficulty of randomizing subjects to levels of the
      mediator (MacKinnon, 2008). The focus of this paper is how incorporating
      longitudinal measures of the mediating and outcome variables aides in the causal
      interpretation of mediated effects. This paper provides useful SAS(r) tools for
      designing adequately powered studies to detect the mediated effect. Three SAS
      macros were developed using the powerful but easy-to-use REG, CALIS, and
      SURVEYSELECT procedures to do the following: (1) implement popular statistical
      models for estimating the mediated effect in the pretest-posttest control group
      design; (2) conduct a prospective power analysis for determining the required
      sample size for detecting the mediated effect; and (3) conduct a retrospective
      power analysis for studies that have already been conducted and a required sample
      to detect an observed effect is desired. We demonstrate the use of these three
      macros with an example.

PMID- 30215061
TI  - Ground-state molecular and electronic structures of group-IV nanoribbons,
      nanorings and nanotubes.
AB  - Based on ab initio molecular orbital (MO) theory and first-principles band
      calculations, we systematically study the ground-state molecular and electronic
      structures of group-IV nanoribbons (NRBs), nanorings (NRGs) and nanotubes (NTBs)
      by substituting the honeycomb skeletal atoms with C, Si or Ge atoms. We then
      explore the energetics in the ground-state singlet-triplet (ST) crossover,
      particularly focusing on the configuration hybridization by electron correlation.

PMID- 30215062
TI  - Smoothing the single-crystal to single-crystal conversions of a two-dimensional
      metal-organic framework via the hetero-metal doping of the linear trimetallic
      secondary building unit.
AB  - The two-dimensional (2D) metal-organic framework (MOF)
      [Cd2.25Co0.75(BTB)2(DEF)4].2(DEF)0.5 (1a, BTB = benzene-1,3,5-tribenzolate; DEF =
      N,N'-diethylformamide) featuring linear trimetallic cluster secondary building
      units (SBUs) and replaceable DEF solvates reacts smoothly with dipyridyl ligands
      DPS, DPDS, and BIPY (DPS = 4,4'-dipyridyl sulfide; DPDS = 4,4'-dipyridyl
      disulfide; BIPY = 4,4'-bipyridine), yielding three-dimensional (3D) non
      interpenetrated [Cd2.25Co0.75(BTB)2(DPS)2].xSol (2) and
      [Cd2.25Co0.75(BTB)2(DPDS)2].xSol (3), and interpenetrated
      [Cd2.25Co0.75(BTB)2(BIPY)(H2O)2].xSol (4). The smooth conversion of 1a to 3
      contrasts the drastic single-crystal to single-crystal (SCSC) conversion observed
      for the homometallic [Cd3(BTB)2(DEF)4].2(DEF)0.5 (1b), presumably due to the
      presence of the relatively Lewis acidic Co2+ that lessens the propensity for
      binding by soft dipyridyl donors. Activated samples of 2-4 showed no obvious
      absorption of N2 at 77 K, but reversible type I uptake of CO2 at 195 K.

PMID- 30215063
TI  - Merging base-promoted C-C bond cleavage and iron-catalyzed skeletal rearrangement
      involving C-C/C-H bond activation: synthesis of highly functionalized carbazoles.
AB  - An efficient and atom-economical methodology for the synthesis of multi
      substituted carbazoles starting from alpha-aryl ketones and ynones under mild
      reaction conditions has been developed. This process goes through Cs2CO3 promoted
      C-C sigma-bond activation of alpha-aryl ketones followed by highly selective C-H
      bond activations and C-C bond fragmentations in a one-pot operation.

PMID- 30215064
TI  - One pot synthesis of alpha-AgVO3/palygorskite nanocomposites with enhanced
      photocatalytic activity using triple roles of palygorskite: supporter, dispersant
      and growth-directing agent.
AB  - Novel alpha-AgVO3/palygorskite nanocomposites were successfully prepared via a
      one pot deposition precipitation method. The 1D natural palygorskite
      nanoarchitectures served as an excellent supporting matrix, dispersant and growth
      directing agent for the in situ loading of alpha-AgVO3 nanoparticles. Both the
      photocatalytic activity of the composites and the effect of the amount of
      palygorskite were investigated. The obtained 0D-1D alpha-AgVO3/palygorskite
      nanocomposites exhibited remarkably enhanced performance for photocatalytic
      degradation of rhodamine B (RhB) compared to pristine alpha-AgVO3 microbars under
      visible light irradiation. alpha-AgVO3/palygorskite composites with 40 wt% of
      palygorskite exhibited optimal photocatalytic activity for the degradation of
      RhB, which was approximately 6 times as high as that of pure alpha-AgVO3.
      Moreover, the optimal alpha-AgVO3/palygorskite nanocomposites also showed better
      photocatalytic disinfection activity of E. coli than pure alpha-AgVO3. The
      enhanced photocatalytic activity of the alpha-AgVO3/palygorskite composites
      should be attributed to the intimate contact resulting from electrostatic
      interaction between negatively charged palygorskite and alpha-AgVO3; the enhanced
      adsorption, absorption capability and valid dispersion with the introduction of
      palygorskite resulted in the decrease of alpha-AgVO3 nanoparticles' size and the
      effective transfer and separation of the photogenerated charge carriers. This
      work could provide a new clue for designing natural mineral based highly
      efficient visible-light responding photocatalysts for the organic pollutant
      degradation and bacteria inactivation.

PMID- 30215065
TI  - Observation of current rectification by the new bimetallic iron(iii) hydrophobe
      [Fe(LN4O6)] on Au|LB-molecule|Au devices.
AB  - Targeting the development of stimulus-responsive molecular materials with
      electronic functionality, we have synthesized and studied the redox and
      electronic properties of a new bimetallic iron hydrophobe [FeIII2(LN4O6)] (1).
      The new H6LN4O6 ligand displays bicompartmental topology capable of accomodating
      two five-coordinate HSFeIII ions bridged by tetraaminobenzene at a close distance
      of ca. 8 A. We show that the metal-based reduction processes in (1) proceed
      sequentially, as observed for electronically coupled metal centers. This species
      forms a well-defined Pockels-Langmuir film at the air-water interface, with
      collapse pressure of 32 mN m-1. Langmuir-Blodgett monolayers were deposited on
      gold substrates and used to investigate current-voltage (I-V) measurements. This
      unprecedented bimetallic hydrophobe [FeIII2(LN4O6)] (1) shows unquestionable
      molecular rectification and displays a rectification ratio RR between 2 and 15.

PMID- 30215066
TI  - Fe-Catalyzed three-component carboazidation of alkenes with alkanes and
      trimethylsilyl azide.
AB  - Reported herein is a novel iron-catalyzed, DTBP-mediated carboazidation of
      alkenes using cycloalkanes, CH2Cl2, CHCl3 and CCl4 as alkylating reagents to
      generate electrophilic or nucleophilic alkyl radicals. Mechanistic studies
      suggested that the reaction proceeded via the addition of alkyl radicals to
      alkenes followed by an iron-mediated ligand transfer process. The reaction is
      unique as it is applicable not only to diversely functionalized electron rich
      alkenes, but also to electron-poor olefins to provide chain extended azides and
      gamma-azido chloroalkanes in good to high yields.

PMID- 30215072
TI  - Visible light-promoted umpolung coupling of aryl tri-/difluoroethanones with 2
      alkenylpyridines.
AB  - Tertiary alcohols bearing a trifluoromethyl group are of considerable medicinal
      interest. Using an umpolung strategy, we herein report the first intermolecular
      reductive cross-coupling of aryl tri-/difluoroethanones with 2-alkenylpyridines
      with the aid of a Bronsted acid catalyst upon visible-light irradiation. This
      metal-free reaction is operationally simple and performed at ambient temperature,
      allowing access to desired tertiary alcohols with tri-/difluoromethyl groups in
      moderate to excellent yields. The commercially available and easily handled
      Hantzsch ester effectively serves as an electron donor, as well as a hydrogen
      atom source.

PMID- 30215073
TI  - Cyclopeptidic photosensitizer prodrugs as proteolytically triggered drug delivery
      systems of pheophorbide A: part I - self-quenched prodrugs.
AB  - Herein, we report the synthesis of a new prodrug system consisting of
      regioselectively addressable functionalized templates bearing multiple
      pheophorbide A moieties for use in photodynamic therapy. These coupling reactions
      were achieved using copper-free "click" chemistry, namely a strain-promoted azide
      alkyne cycloaddition. This new design was used to obtain well-defined quenched
      photosensitizer prodrugs with perfect knowledge of the number and position of
      loaded photosensitizers, providing structures bearing up to six photosentitizers
      and two PEG chains. These conjugates are ideally quenched in their native state
      regarding their fluorescence emission (up to 155 +/- 28 times less fluorescent
      for an hexasubstituted conjugate than a monosubstituted non-quenched reference
      compound) or singlet oxygen production (decreased 8.7-fold in the best case) when
      excited. After 2 h of proteolytic activation, the fluorescence emission of a
      tetrasubstituted conjugate was increased 17-fold compared with the initial
      fluorescence emission.

PMID- 30215080
TI  - Magnetic nanoparticles loaded with functional RNA nanoparticles.
AB  - RNA is now widely acknowledged not only as a multifunctional biopolymer but also
      as a dynamic material for constructing nanostructures with various biological
      functions. Programmable RNA nanoparticles (NPs) allow precise control over their
      formulation and activation of multiple functionalities, with the potential to
      self-assemble in biological systems. These attributes make them attractive for
      drug delivery and therapeutic applications. In the present study, we demonstrate
      the ability of iron oxide magnetic nanoparticles (MNPs) to deliver different
      types of RNA NPs functionalized with dicer substrate RNAs inside human cells. Our
      results show that use of functionalized RNA NPs result in statistically higher
      transfection efficiency compared to the use of RNA duplexes. Furthermore, we show
      that the nucleic acids in the MNP/RNA NP complexes are protected from nuclease
      degradation and that they can achieve knockdown of target protein expression,
      which is amplified by magnetic stimulus. The current work represents the very
      first report indicating that iron oxide nanoparticles may efficiently protect and
      deliver programmable RNA NPs to human cells.

PMID- 30215074
TI  - Bioinspired structural transition of synthetic polymers through biomolecular
      ligand binding.
AB  - Inspired by ligand binding-triggered structural transition of biopolymers in
      living systems, we demonstrated the structural transition of thermoresponsive
      poly(N-isopropylacrylamide) through specific ligand binding of artificially
      evolved peptides to the polymer.

PMID- 30215081
TI  - Superatom chemistry: promising properties of near-spherical noble metal clusters.
AB  - Properties of near-spherical metal clusters are best understood on the basis of
      the concept of conventional atoms. Their conduction electrons occupy cluster
      orbitals that remind of hydrogen-like orbitals since they have the same angular
      dependence. When populated with electrons, maxima in their ionization potentials
      and minima in electron affinities reveal the closing of shells in the same sense
      as for noble gases. This suggests that the periodic table of elements should be
      amended by a third dimension reflecting the number of atoms in a cluster of the
      element. In a bonded situation the symmetry of cluster atoms is broken, and the
      atomic orbital momentum is quenched to a large extent. However, if superatoms are
      axially symmetric, there are superatomic orbital angular moments that are locked
      along this symmetry axis. If their z-component is non-zero, this leads to large
      magnetic moments and to significant spin-orbit interactions, which greatly
      complicate spectroscopic observation. This magnetic interaction is anisotropic
      and may lead to hysteresis loops with corresponding blocking temperatures up to
      room temperature. The number of unpaired electrons in such a system is crucial,
      and it may be influenced by doping with different atoms or by chemical bonds to
      capping ligands. Stable superatom clusters with size-tuned, tailored band gaps
      and band edge energies may be attractive replacements for toxic or rare elements
      in photovoltaic cells or batteries; they form chemically inert and well-defined
      stoichiometric complexes with various ligands. This reminds of the established
      transition metal complexes and may lead to a novel branch of chemistry in which
      the central ion of organometallic complexes is replaced by a metal superatom.

PMID- 30215082
TI  - 2D europium coordination polymer as a regenerable fluorescence probe for
      efficiently detecting fipronil.
AB  - Recently, considerable attention has been paid to European eggs that were found
      to contain the poisonous insecticide fipronil. Excessive consumption of fipronil
      can harm the human body, in particular, the liver, thyroid, nervous system and
      kidneys. As a consequence, there is an urgent need to develop a method to detect
      fipronil. In this work, a lanthanide coordination polymer [Eu(SIP)(H2O)4]n (1)
      (NaH2SIP = 5-sulfoisophthalic acid monosodium salt) was synthesized and
      characterized by single-crystal X-ray crystallography, elemental analysis,
      infrared spectrum and powder X-ray diffractions. The X-ray studies show that 1 is
      a two-dimensional layered structure, which is constructed of fused
      {[Eu(H2O)4]3(SIP)3} pseudo-hexagonal grids. The luminescence properties of 1
      exhibit effective recognition for fipronil in methanol solution. Furthermore, a
      wide linear range (10-6-10-4 M), a low detection limit of 0.8 MUM, high
      selectivity and excellent recyclability, reveal that 1 can potentially act as a
      luminescence-based sensor for quantitative and highly sensitive detection of
      fipronil. To the best of our knowledge, it is the first time that a metal-organic
      coordination polymer, as a fluorescent-based probe, has been used for the
      detection of fipronil. Moreover, fluorescent-based test papers of 1 have also
      been prepared, which can be regarded as a simple and practical method for
      detecting fipronil.

PMID- 30215083
TI  - Photophysical properties of a D-pi-A Schiff base and its applications in the
      detection of metal ions.
AB  - A D-pi-A Schiff-base compound, 2-amino-3({[4-(diethylamino)-2
      hydroxylphenyl]methylene}amino)-but-2-enedinitrile (H2L), was prepared using
      diaminomaleonitrile and 4-(N,N-diethylamino)salicylaldehyde. Compared with H2L at
      293 K, a low temperature of 100 K makes the parallel aromatics in H2L come closer
      and fluorescence emission becomes weaker because of pi-pi interaction-caused
      quenching. After grinding the crystals of H2L, the colour changed from dark brown
      red to yellow under room light and the fluorescence emission enhanced about 9
      fold due to the damage of the intermolecular hydrogen bonds, leading to a
      decrease of non-radiative transition. H2L showed aggregation-induced emission
      enhancement (AIEE) characteristics in THF/H2O, whose mechanism is attributed to
      the restriction of intramolecular rotation (RIR). The UV-Vis spectra of H2L with
      Cu2+ in THF/H2O showed that at first a CuL complex was formed and subsequently a
      CuL' complex (H2L' = N',N'-bis(4-N',N'-diethylsalicylidene) ethylenediamine) was
      obtained. The CuL complex turned into the CuL' complex as time prolonged. H2L
      acted as a dual channel chemosensor for Cu2+ ions in THF/HEPES (v/v: 2 : 8, pH =
      8.0) and the CuL complex was stable in this medium. H2L is also a naked-eye probe
      for Mn2+ ions in CH3CN. The limits of detection are much lower than the allowable
      level of copper(ii) and manganese(ii) in drinking water set by the World Health
      Organization (WHO).

PMID- 30215084
TI  - Detection of bacterial contamination in food matrices by integration of quorum
      sensing in a paper-strip test.
AB  - There are an estimated 48 million cases of foodborne illness in the United States
      every year. In general, these illnesses are the result of unintentional
      contamination and improper food handling. Because bacterial contamination plays a
      major role in food spoilage and, hence, in foodborne illnesses, it is important
      to design easy, portable methods to detect bacteria in food. Quorum sensing (QS)
      enables bacteria to communicate with one another and by doing so they can
      modulate their behavior in a cell-density dependent manner. In bacteria, quorum
      sensing molecules (QSMs) are known to control several factors such as virulence
      factor production, antibiotic production, biofilm formation, and gene regulation.
      Herein, we demonstrate the applicability of whole cell biosensing systems for the
      early identification of food contamination via detection of QSMs. Additionally,
      we have developed a portable system for detection of bacterial contamination
      using microdots of immobilized whole cell-based biosensors on paper that boast
      nanomolar level detection of QSMs in two different food matrices, namely beef and
      milk. Limits of detection ranged from 1 * 10-7 M to 1 * 10-9 M with relative
      standard deviations (RSDs) of 1-16%. This rapid, easy, and portable test could be
      a useful tool for use in the field and during all stages of food manipulation,
      i.e., from farms to distribution, storage, sales, and preparation prior to
      consumption, to ensure that food is free of bacterial contamination.

PMID- 30215085
TI  - Confinement-driven radical change in a sequence of rotator phases: a study on n
      octacosane.
AB  - Rotator-phase forming n-alkanes have been studied extensively in both their bulk
      state and in nanoconfinement. While some alkanes maintain their bulk-state
      rotator phases in nanoconfinement albeit with increased disorder, there are
      others exhibiting new rotator phases upon confinement. We present here a
      temperature dependent X-ray diffraction (XRD) and differential scanning
      calorimetric (DSC) study on n-octacosane (C28H58), which almost completely loses
      its bulk state RIV phase and undergoes complete disappearance of its RIII phase.
      In their place, when confined in cylindrical anodized alumina nanopores, a phase
      highly resembling the hexatic mesophase is formed at a higher temperature and the
      RI rotator phase at a lower temperature. The effects of finite size, interfacial
      interactions with the host matrix and alkyl chain flexibility are used to provide
      an explanation for such unexpected behaviour.

PMID- 30215086
TI  - Molecular iodine-mediated synthesis of thiocarbamates from thiols, isocyanides
      and water under metal-free conditions.
AB  - A simple and practical molecular iodine-mediated method for the efficient
      construction of thiocarbamates from isocyanides, thiols and water under metal
      free and mild conditions has been developed. A variety of thiocarbamates were
      easily synthesized through this methodology, which has the advantages of simple
      operation, eco-friendly conditions, good functional group tolerance, and readily
      accessible raw materials.

PMID- 30215087
TI  - A hierarchical CoTe2-MnTe2 hybrid nanowire array enables high activity for oxygen
      evolution reactions.
AB  - In this communication, we demonstrate the development of hierarchical CoTe2-MnTe2
      hybrid nanowires grown on Ti mesh (CoTe2-MnTe2/TM) as an electrocatalyst for the
      oxygen evolution reaction. The catalyst exhibits excellent conductivity and
      exposes sufficient active sites derived from its favorable composition and
      structure, which only needs an overpotential of 310 mV to drive a current density
      of 50 mA cm-2 in 1.0 M KOH.

PMID- 30215088
TI  - Mercury ion-DNA specificity triggers a distinctive photoluminescence depression
      in organic semiconductor probes guided with a thymine-rich oligonucleotide
      sequence.
AB  - DNA strands have been recently found to play a role in crystallizing organic
      semiconductors as a substitute for conventional surfactants. Such DNA-guided
      organic semiconductor particles possessed the recognition ability to
      complementary target DNAs, resulting in "enhanced luminescence" due to the lesser
      degree of non-radiative dissipation. Apart from this, in this study we developed
      selective recognition of mercury ions by utilizing DNA probes having ion-specific
      thymine-rich motifs. Strikingly, the specific ion-DNA interaction triggered
      rather distinctive "depressed luminescence" emitting from the particles. The
      mercury ions were found to be present both at the surface and the inner regions,
      which were discovered to relate to the drastic morphological distortion of the
      particles as evidenced by elemental, electron microscopy, and confocal
      fluorescence microscopy analyses. This novel phenomenon discovered would expand
      the technological values of organic semiconductors conjugated with
      oligonucleotides toward a wider range of target-specific applications.

PMID- 30215089
TI  - The effect of core-shell engineering on the energy product of magnetic
      nanometals.
AB  - Solution-based growth of magnetic FePt-FeCo (core-shell) nanoparticles with a
      controllable shell thickness has been demonstrated. The transition from spin
      canting to exchange coupling of FePt-FeCo core-shell nanostructures leads to a
      28% increase in the coercivity (12.8 KOe) and a two-fold enhancement in the
      energy product (9.11 MGOe).

PMID- 30215090
TI  - Cyclopeptidic photosensitizer prodrugs as proteolytically triggered drug delivery
      systems of pheophorbide A: part II - co-loading of pheophorbide A and black hole
      quencher.
AB  - Previously, we have shown that the use of a cyclopeptidic carrier could be of
      great interest for the design of fully characterized prodrugs for further use in
      photodynamic therapy. In order to further optimize the design, we decided to
      modify the highly quenched conjugate uPA-cPPP4/5 by co-loading a long-distance
      fluorescence quencher. For this purpose we tethered two black hole quenchers
      (BHQ3) together with two pheophorbide A moities onto the same PEGylated backbone
      and assessed the modified photophysical properties. In addition, to prove the
      reliability of our concept, we designed two analogues, uPA-cPPQ2+2/5 and CathB
      cPPQ2+2/5, by using two different peptidic linkers as substrates for uPA and
      cathepsin B, respectively. These two conjugates proved to be much more water
      soluble than their analogues bearing only Phas. These conjugates are not only
      highly quenched in their native state with regard to their fluorescence emission
      (up to 850 +/- 287 times less fluorescent for CathB-cPPQ2+2/5 as compared to the
      unquenched monosubstituted reference uPA-cPPP1/5), but also prevent singlet
      oxygen production (with a total quenching of the emission when the quenchers are
      co-loaded with photosensitizers) when the photosentistizers are excited. After
      proteolytic activation, these conjugates recover their photophysical properties
      in the same way as occurred for uPA-cPPP4/5, with up to a 120-fold increase in
      fluorescence emission for uPA-cPPQ2+2/5 after two hours of incubation with uPA.

PMID- 30215091
TI  - Catalytic regeneration of a Th-H bond from a Th-O bond through a mild and
      chemoselective carbonyl hydroboration.
AB  - Here we present an unprecedented chemoselective hydroboration for aldehydes and
      ketones catalysed by actinides. The reaction features a very low catalyst loading
      (0.1-0.004 mol%) and quantitative product formation in less than 15 minutes, at
      room temperature. Thermodynamic and kinetic studies including stoichiometric and
      labeling studies with deuterated pinacolborane allow us to propose a plausible
      mechanism for this remarkable catalytic regeneration of a Th-H bond via carbonyl
      hydroboration.

PMID- 30215092
TI  - Choline-mediated synthesis of zeolite ERS-7 via an excess fluoride approach.
AB  - A high-silica (Si/Al = 14) version of zeolite ERS-7 has been synthesized using
      choline as an organic structure-directing agent (OSDA) via an excess fluoride
      approach, and the physicochemical properties of this cage-based small-pore
      material and its catalytic and adsorption properties are evaluated.

PMID- 30215094
TI  - Why 0.9% saline is isotonic: understanding the aqueous phase of plasma and the
      difference between osmolarity and osmolality.

PMID- 30215093
TI  - Functional recovery after surgical stabilization and postoperative radiotherapy
      due to metastases of long bones.
AB  - PURPOSE: To reinvestigate the functional recovery after combined treatment with
      surgery and postoperative irradiation of complete or impending pathologic
      fractures of long bones. METHODS: We retrospectively evaluated the results of
      external beam radiation therapy (EBRT) carried out after 68 orthopedic
      stabilization procedures (femur, n = 55, 80.8%; humerus, n = 13, 19.2%) for
      actual or impending pathological fracture of long bone in 61 patients with
      skeletal metastases. The mean normalized total dose was 34.7 +/- 7.8 Gy.
      Endpoints were patient's functional status (FS; 1 = normal pain free status; 2 =
      normal use with pain; 3 = significantly limited used; 4 = nonfunctional status),
      a need for a secondary procedure to the same site and overall survival following
      surgery. RESULTS: Overall, 75% of patients achieved normal functional status (FS
      1-2) within 12 weeks after surgery. Functional recovery in surviving patients
      reached 93%. Median survival was 17 months (95% confidence interval 13.7-20.2).
      Secondary surgical intervention at the same location was necessary in 3 patients
      (4.4%). On multivariate analysis, only general status (p = 0.011) and growing
      potential of primary tumor (p = 0.049) were associated with achieving normal
      functional status within 12 weeks after surgery and radiotherapy. The applied
      radiation schemes demonstrated a comparable impact on functional recovery.
      CONCLUSIONS: Our results confirm the effectiveness of stabilizing surgery and
      fractionated postoperative radiotherapy in terms of functional recovery,
      supporting prior results assessing postsurgical radiotherapy versus follow-up.
      The patient's general status is a strong prognostic factor for functional
      recovery. Rapidly growing tumors may hinder achievement of a normal functional
      status.

PMID- 30215095
TI  - Fundamental insights into autosomal dominant polycystic kidney disease from human
      based cell models.
AB  - Several animal- and human-derived models are used in autosomal dominant
      polycystic kidney disease (ADPKD) research to gain insight in the disease
      mechanism. However, a consistent correlation between animal and human ADPKD
      models is lacking. Therefore, established human-derived models are relevant to
      affirm research results and translate findings into a clinical set-up. In this
      review, we give an extensive overview of the existing human-based cell models. We
      discuss their source (urine, nephrectomy and stem cell), immortalisation
      procedures, genetic engineering, kidney segmental origin and characterisation
      with nephron segment markers. We summarise the most studied pathways and lessons
      learned from these different ADPKD models. Finally, we issue recommendations for
      the derivation of human-derived cell lines and for experimental set-ups with
      these cell lines.

PMID- 30215096
TI  - Pediatric residents' simulation-based training in patient safety during sedation.
AB  - In Israeli emergency departments, pediatric residents are allowed to
      independently perform procedural sedation after training. Preparing the residents
      to practice unsupervised sedations requires participation in a simulation-based
      training in patient safety during sedation (STPSDS). The study objective was to
      evaluate participants' perception of knowledge and confidence from the STPSDS. We
      performed a retrospective analysis of participants' self-reported perception of
      knowledge acquisition. At the end of each course, participants were requested to
      rate, anonymously and independently, the training contribution to their knowledge
      and confidence using a four-point Likert scale. Between January 2010 and December
      2017, 321 pediatric residents participated in 67 STPSDS courses; 315 completed
      the self-assessments. Participants' median responses of the training contribution
      were 4 (IQR 3-4) for overall knowledge, 4 (IQR 4-4) for understanding potential
      complications during sedation, 3 (IQR 3-4) for knowledge in managing adverse
      events, and 3 (IQR 2-4) for knowledge in practicing safe sedation. Median
      response for contribution to participants' confidence in performing sedation was
      3 (IQR 3-4).Conclusion: We found that the STPSDS improved perception of knowledge
      and confidence among pediatric residents. Our findings suggest that this training
      has a valuable role in preparing pediatric residents to practice unsupervised
      sedations in the ED. What is Known: * In Israel, sedation-trained pediatric
      residents performed sedations in the Emergency Department * Successful completion
      of a simulation-based training in patient safety during sedation (STPSDS) is a
      mandatory requirement to perform unsupervised sedation. What is New: * The STPSDS
      improved perception of knowledge and confidence among pediatric residents. * This
      training may be valuable in preparing pediatric residents to practice
      unsupervised sedations.

PMID- 30215098
TI  - Genetics of antigen processing and presentation.
AB  - Immune response to disease requires coordinated expression of an army of
      molecules. The highly polymorphic MHC class I and class II molecules are key to
      control of specificity of antigen presentation. Processing of the antigen, to
      peptides or other moieties, requires other sets of molecules. For classical class
      I, this includes TAP peptide transporters, proteasome components and Tapasin,
      genes which are encoded within the MHC. Similarly, HLA-DO and -DM, which
      influence presentation by HLA class II molecules, are encoded in the MHC region.
      Analysis of MHC mutants, including point mutations and large deletions, has been
      central to understanding the roles of these genes. Mouse genetics has also played
      a major role. Many other genes have been identified including those controlling
      expression of HLA class I and class II at the transcriptional level. Another
      genetic approach that has provided insight has been the analysis of
      microorganisms, including viruses and bacteria that escape immune recognition by
      blocking these antigen processing and presentation pathways. Here, we provide a
      brief history of the genetic approaches, both traditional and modern, that have
      been used in the quest to understand antigen processing and presentation.

PMID- 30215099
TI  - The pararectus approach for internal fixation of acetabular fractures involving
      the anterior column: evaluating the functional outcome.
AB  - INTRODUCTION: Aim of this retrospective analysis of prospectively collected data
      was to evaluate the functional mid-term outcome two years after open reduction
      and internal fixation of acetabular fractures involving the anterior column with
      affection of the quadrilateral plate using the pararectus approach on a large
      cohort. METHOD: Fifty-two patients (12 female, 40 male) with a median age of 55
      (range 18-90) years and displaced acetabular fractures involving the anterior
      column were surgically treated in a single level I trauma centre between July
      2012 and February 2016 using the pararectus approach. Thirty-four patients (8
      female and 26 male) with a median age of 58 (range 20-85) years were available
      for complete clinical follow-up at regular intervals, finally 24 months post
      operatively. Functional outcome was evaluated according to modified Merle
      d'Aubigne score, Lower Extremity Functional Scale, WOMAC, and SF-36. RESULTS:
      Range of time between trauma and surgical treatment was three (range 0-19) days.
      Operation time was 140 (range 60-240) minutes, and duration of hospital treatment
      was 19 (range 7-38) days. Functional results in 34 patients available for final
      follow-up demonstrated 68 points (median; range 39-80) according to the Lower
      Extremity Functional Scale, 6% according to the WOMAC (mean; SD +/- 14.5%), and
      69% (mean; SD +/- 20.1%) according to the SF-36. The modified Merle d'Aubigne
      score was excellent in 22 patients, good in eight patients, and fair in four
      patients. DISCUSSION/CONCLUSION: Based on the good to excellent functional mid
      term follow-up results of this study, the pararectus approach can be recommended
      as sufficient alternative single access to address displaced acetabular fractures
      involving the anterior column, independent of patients' age.

PMID- 30215100
TI  - Outcomes after knee arthroplasty in extra-articular deformity.
AB  - PURPOSE: To assess functional outcomes in patients undergoing total knee
      arthroplasty (TKA) without previous corrective osteotomy for treatment of knee
      osteoarthritis associated with extra-articular deformity. METHODS: From January
      to December 2016, patients with knee osteoarthritis with extra-articular
      deformities who presented for preoperative assessment before TKA were evaluated
      prospectively. Physical and radiological characteristics were documented pre- and
      postoperatively. RESULTS: TKA was performed in 33 knees; 25 were considered for
      analysis. The mean age was 65.2 years (range, 48-79 years). Sixteen deformities
      were secondary to fractures and nine to failed osteotomies. The mean Knee Society
      Score (KSS) improved from 27.1 pre-operatively to 68.7 post-operatively (p =
      0.000). Pre-operative mechanical axis ranged from 32 degrees  varus (negative) to
      26 degrees  valgus. After correction, 20 knees were within 3 degrees  (varus or
      valgus) of mechanical alignment. CONCLUSION: In patients with extra-articular
      deformities, TKA with asymmetric intra-articular resection and ligament balancing
      can relieve pain and realign the mechanical axis of the lower limb.

PMID- 30215097
TI  - A new immunodeficient retinal dystrophic rat model for transplantation studies
      using human-derived cells.
AB  - PURPOSE: To create new immunodeficient Royal College of Surgeons (RCS) rats by
      introducing the defective MerTK gene into athymic nude rats. METHODS: Female
      homozygous RCS (RCS-p+/RCS-p+) and male nude rats (Hsd:RH-Foxn1mu, mutation in
      the foxn1 gene; no T cells) were crossed to produce heterozygous F1 progeny.
      Double homozygous F2 progeny obtained by crossing the F1 heterozygotes was
      identified phenotypically (hair loss) and genotypically (RCS-p+ gene determined
      by PCR). Retinal degenerative status was confirmed by optical coherence
      tomography (OCT) imaging, electroretinography (ERG), optokinetic (OKN) testing,
      superior colliculus (SC) electrophysiology, and by histology. The effect of
      xenografts was assessed by transplantation of human embryonic stem cell-derived
      retinal pigment epithelium (hESC-RPE) and human-induced pluripotent stem cell
      derived RPE (iPS-RPE) into the eye. Morphological analysis was conducted based on
      hematoxylin and eosin (H&E) and immunostaining. Age-matched pigmented athymic
      nude rats were used as control. RESULTS: Approximately 6% of the F2 pups (11/172)
      were homozygous for RCS-p+ gene and Foxn1mu gene. Homozygous males crossed with
      heterozygous females resulted in 50% homozygous progeny for experimentation. OCT
      imaging demonstrated significant loss of retinal thickness in homozygous rats.
      H&E staining showed photoreceptor thickness reduced to 1-3 layers at 12 weeks of
      age. Progressive loss of visual function was evidenced by OKN testing, ERG, and
      SC electrophysiology. Transplantation experiments demonstrated survival of human
      derived cells and absence of apparent immune rejection. CONCLUSIONS: This new rat
      animal model developed by crossing RCS rats and athymic nude rats is suitable for
      conducting retinal transplantation experiments involving xenografts.

PMID- 30215101
TI  - The interplay of context factors in hypnotic and sedative prescription in primary
      and secondary care-a qualitative study.
AB  - PURPOSE: Non-medical or contextual factors strongly influence physicians'
      prescribing behavior and may explain why drugs, such as benzodiazepines and Z
      drugs, are still frequently prescribed in spite of well-known adverse effects.
      This study aimed to explore which contextual factors influence the prescription
      of hypnotics and sedatives and to compare their role in primary and secondary
      care. METHODS: Understanding medical practices as games with specific rules and
      strategies and performed in a largely habitual, not fully conscious manner, we
      asked a maximum variation sample of 12 hospital doctors and 12 general
      practitioners (GPs) about their use of hypnotics and sedatives. The interviews
      were analyzed by qualitative content analysis. RESULTS: Hospital doctors' and
      GPs' use of hypnotics and sedatives was influenced by a variety of contextual
      factors, such as the demand of different patient groups, aims of management, time
      resources, or the role of nurses and peers. Negotiating patient demands,
      complying with administrative regulations, and finding acceptable solutions for
      patients were the main challenges, which characterized the game of drug use in
      primary care. Maintaining the workflow in the hospital and finding a way to
      satisfy both nurses and patients were the main challenges in secondary care.
      CONCLUSIONS: Even if doctors try to act rationally, they cannot escape the
      interplay of contextual factors such as handling patient needs, complying with
      administrative regulations, and managing time resources. Doctors should balance
      these factors as if they were challenges in a complex game and reflect upon their
      own practices.

PMID- 30215102
TI  - FKBP1A rs6041749 polymorphism is associated with allograft function in renal
      transplant patients.
AB  - AIM: To investigate the potential impact of single-nucleotide polymorphisms
      (SNPs) in the FK506-binding protein (FKBP)-calcineurin (CaN)-nuclear factor of
      activated T cells (NFAT) signaling pathway on the efficacy and safety of
      tacrolimus (TAC) in Chinese renal transplant patients. METHODS: Seventy-seven tag
      SNPs were detected in 146 patients who were on TAC-based maintenance
      immunosuppression and who followed up for at least 2 years. The relationships of
      these polymorphisms with clinical outcomes such as acute rejection, acute
      nephrotoxicity, pneumonia, and estimated glomerular filtration rate (eGFR) were
      explored. For the FKBP1A rs6041749 polymorphism, which has a significant
      association with renal function over time, a preliminary functional analysis was
      performed using a dual-luciferase reporter gene system. RESULTS: The patients
      with FKBP1A rs6041749 TT genotype had a more stable eGFR level than CC and CT
      carriers (P = 2.08 * 10-8) during the 2 years following transplantation. Dual
      luciferase reporter assay results showed that the rs6041749 C variant could
      enhance the relative luciferase activity compared with the T variant, which
      indicated that the rs6041749 C allele may increase the FKBP1A gene transcription.
      In addition, we did not find any association between these genetic variants and
      the risk of acute rejection, acute nephrotoxicity, and pneumonia in renal
      transplant patients receiving TAC-based immunosuppression. CONCLUSIONS: FKBP1A
      rs6041749 C allele carriers are at higher risk for eGFR deterioration. The
      variant might serve as a biomarker to predict allograft function in renal
      transplant patients.

PMID- 30215103
TI  - [Time trends of occupational differences in smoking behaviour of employed men and
      women in Germany : Results of the 1999-2013 microcensus].
AB  - BACKGROUND: Studies show that people with a low occupational status are more
      likely to smoke than those with a high occupational status. Against the
      background of a general decline in tobacco consumption, time trends of
      occupational differences in smoking behaviour of employed men and women in
      Germany were examined. METHODS: The analyses were based on the last five waves of
      the German microcensus that included questions about smoking (1999, 2003, 2005,
      2009 and 2013), taking only employed men and women aged 18-64 years into account
      (n = 688,746). Information on occupational position was summarised using
      international classifications of occupation (ISEI-08 and ISCO-08). Raw and model
      based standardized prevalence estimates of current smoking were calculated.
      RESULTS: Between 1999 and 2013, the proportion of smokers in the working
      population fell from 39.9 to 34.4% (men) and from 30.6 to 26.8% (women).
      Differences between occupational status groups increased significantly: while the
      prevalence of smoking among employees with high occupational status decreased, it
      remained largely stable in the low status group. In 2013, the occupations with
      the highest proportion of smokers were waste disposal workers, cleaning staff,
      unskilled workers, truck and bus drivers, salespeople and cashiers, and employees
      in the catering industry. CONCLUSION: Since the beginning of the 2000s, the
      prevalence of smoking in the working population has declined. The strengthened
      tobacco control policy - e. g. the establishment of smoke-free workplace laws -
      might have contributed to this trend. In the context of workplace health
      promotion, tobacco prevention and cessation measures should be targeted at those
      professions in which smoking is still particularly common.

PMID- 30215104
TI  - [Trends in smoking among adults in Germany : Evidence from seven population-based
      health surveys from 1991-2015].
AB  - BACKGROUND: Despite decreasing smoking prevalence, tobacco use remains a key
      public health problem in Germany. For planning, managing, and evaluating tobacco
      control measures, regular data collection on smoking behavior in the population
      is essential. The aim of this article is to present trends in adult tobacco use
      since the early 1990s based on data from the health monitoring of the Robert Koch
      Institute (RKI). METHODS: Analyses are based on data from 106,158 individuals
      aged 18 to 79 years, who participated in seven RKI health surveys from 1991-2015.
      Trends in tobacco consumption were analyzed using different indicators of smoking
      behavior, stratified by age, cohort, and gender. RESULTS: An overall falling
      smoking prevalence can be attributed primarily to a significant decline in the
      younger age groups since the early 2000s. Trend analysis by cohort reveals a
      declining prevalence for almost all cohorts over time from 1991-2015.
      Historically there has been is a sharp increase in the prevalence of women who
      have ever smoked between the 1930-1934 and 1950-1959 cohorts. The proportion of
      men who have ever smoked slightly decreased between the 1930-1934 and 1980-1984
      cohorts. DISCUSSION: The shown overall decline happened concurrently with various
      tobacco prevention measures implemented during this period in Germany. If present
      trends related to continuous high smoking rates are sustained, it can be assumed
      that the tobacco consumption of the population will remain the source of adverse
      health outcomes. Accordingly, tobacco prevention measures and the promotion of
      smoking cessation in all age groups should be a public health priority.

PMID- 30215105
TI  - Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer
      activity.
AB  - OBJECTIVE: To determine the role of brown adipose tissue (BAT) in cancer
      activity. MATERIALS AND METHODS: The study group comprised 142 patients (121
      female, 21 male; mean age, 49 +/- 16 years) who underwent F18-FDG PET/CT (PET/CT)
      for staging or surveillance of cancer and who were BAT-positive on PET/CT. BAT
      volume by PET/CT, abdominal (visceral and subcutaneous) fat and paraspinous
      muscle cross-sectional areas (CSA) were assessed. Groups with and without active
      cancer on PET/CT were compared using a two-sided paired t test. Linear regression
      analyses between BAT and body composition parameters were performed. RESULTS:
      There were 62 patients (54 female, eight male) who had active cancer on PET/CT
      and 80 patients (67 female, 13 male) without active cancer. Groups were similar
      in age and BMI (p >= 0.4), abdominal fat and muscle CSA, fasting glucose, and
      outside temperature at time of scan (p >= 0.2). Patients who had active cancer on
      PET/CT had higher BAT volume compared to patients without active cancer (p =
      0.009). In patients without active cancer, BAT was positively associated with BMI
      and abdominal fat depots (r = 0.46 to r = 0.59, p < 0.0001) while there were no
      such associations in patients with active cancer (p >= 0.1). No associations
      between BAT and age or muscle CSA were found (p >= 0.1). CONCLUSIONS: BAT
      activity is greater in patients with active cancer compared to age-, sex-, and
      BMI-matched BAT-positive patients without active cancer, suggesting a possible
      role of BAT in cancer activity.

PMID- 30215106
TI  - Partial anterior tunnel syndrome: a retrospective analysis of ultrasound findings
      in four surgically proven cases.
AB  - We present the cases of four patients (two men and two women, mean age of 48.5
      years) with surgically confirmed partial anterior tarsal syndrome, diagnosed by
      ultrasound. All patients reported pain in the dorsal aspect of the forefoot
      radiating to the first intermetatarsal space. Ultrasound showed compression of
      the medial branch of the deep fibular nerve by the extensor hallucis brevis
      tendon at the level of the Lisfranc joint, associated with a hypoechoic neuroma.
      The ultrasound allowed a correct diagnosis to be obtained, which was not evident
      from clinical examination or by standard radiographs (four patients) or MRI
      (three patients). Surgery confirmed the sonographic findings, and all patients
      showed complete recovery.

PMID- 30215107
TI  - [Treatment of Fuchs' endothelial dystrophy with DMEK : Experiences from the past
      10 years].

PMID- 30215108
TI  - [Hearing aid provision in children].
AB  - Achieving high-quality hearing aid fitting in children is an interdisciplinary
      task and a challenge for all involved specialist disciplines. According to
      quality agreements (standards), comparative hearing aid fitting is mandatory
      prior to prescription. Furthermore, RECD measurements and, in older children, in
      situ measurements should be applied on a regular basis for finetuning and
      adjustment of the hearing aid fitting. ENT physicians, phoniatricians and
      pediatric audiologists, pediatric acousticians, teachers of the hearing impaired,
      and special educational needs teachers should work together in an
      interdisciplinary approach.

PMID- 30215109
TI  - Effect of preoperative chemotherapy on distal spread of low rectal cancer located
      close to the anus.
AB  - PURPOSE: This study aimed to clarify the frequency of distal spread and the
      optimal distal margin after preoperative chemotherapy for advanced low rectal
      cancer. METHODS: The study included patients with advanced lower rectal cancer
      who received preoperative chemotherapy and underwent surgery during 2012-2015. We
      investigated the distal spread of tumor cells, defined as the distal distance
      from the intramucosal distal tumor edge to the farthest tumor cells located under
      the submucosal layer. Clinical characteristics were compared for distal spreads
      >= 10 and < 10 mm, and risk factors for distal spread >= 10 mm were investigated.
      RESULTS: Of the 71 patients, 42 (59%) showed distal spread. Distal spreads of 1
      9, 10-19, and >= 20 mm were observed in 27 (38%), 11 (15%), and 4 (6%) patients,
      respectively. Multivariate analysis revealed two independent risk factors for
      distal spread >= 10 mm after preoperative chemotherapy. The first risk factor is
      the presence of different therapeutic effects between the mucosal and deeper
      layers (meaning that superficial tumor shrinkage was evident on colonoscopy, but
      little tumor shrinkage was evident on magnetic resonance imaging) (odds ratio,
      11.6; 95% CI, 2.22-61.3). The second risk factor is poorly differentiated or
      mucinous adenocarcinoma (odds ratio, 8.86; 95% CI, 1.58-49.9). CONCLUSION: A
      distal margin of 20 mm is required (10 mm is insufficient) for advanced lower
      rectal cancer patients who receive preoperative chemotherapy followed by surgery.
      Independent risk factors for distal spread >= 10 mm include (1) the presence of
      different therapeutic effects between mucosal and deeper layers and (2) poorly
      differentiated or mucinous adenocarcinomas.

PMID- 30215110
TI  - Mapping of atrial fibrillation: strategies to understand an enigmatic arrhythmia.
AB  - The three-dimensional (3D) mapping of cardiac arrhythmias has evolved in recent
      years to an important and extremely useful tool, providing important insights
      into arrhythmia mechanisms and thus improving ablation success rates, especially
      in complex arrhythmias. In atrial fibrillation (AF), the most common but also one
      of the most complex cardiac arrhythmias, progress in mapping technology has been
      focusing on several aspects according to the type of AF.In paroxysmal AF,
      important progress in the exact anatomic reconstruction of the main ablation
      target, i.e., the pulmonary veins (PV), has been achieved. Perhaps even more
      importantly, new insights into conduction patterns, such as deceleration at the
      PV ostia, spiral conduction more distally into the PV, and PV cross-talk have
      been detected and enable faster and more sustainable PV isolation.In persistent
      AF, the basic understanding of ongoing AF is perhaps the electrophysiological
      challenge of the 21st century. Since AF is instable in its course, mapping tools
      that assess statistically returning patterns or deal with so-called AF "rotors"
      or "drivers" have been developed, offering unique insights into possible AF
      mechanisms. Refined high-density bi-atrial voltage maps make it possible to
      further characterize the arrhythmogenic substrate and scar zones, while new and
      innovative mapping algorithms enable automated, fast, and reliable annotation of
      up to thousands of electrograms.This improved understanding of AF mechanisms has
      led to the development of promising new ablation strategies, some of which are
      already in use in clinical routine.

PMID- 30215111
TI  - Current concepts and challenges in the radiologic assessment of brain tumors in
      children: part 2.
AB  - Assessing tumor response is a large part of everyday clinical work in
      neuroradiology. However in the setting of tumor treatment, distinguishing tumor
      progression from treatment-related changes is difficult on conventional MRI
      sequences. This is made even more challenging in children where mainstay advanced
      imaging techniques that are often used to decipher progression versus treatment
      related changes have technical limitations. In this review, we highlight the
      challenges in pediatric neuro-oncologic tumor assessment with discussion of
      pseudophenomenon including pseudoresponse and pseudoprogression. Additionally, we
      discuss the advanced imaging techniques often employed in neuroradiology to
      distinguish between pseudophenomenon and true progressive disease.

PMID- 30215112
TI  - Anti-inflammatory and antinociceptive activities of the leaf methanol extract of
      Miconia minutiflora (Bonpl.) DC. and characterization of compounds by UPLC-DAD
      QTOF-MS/MS.
AB  - Some species of the genus Miconia are used in Brazilian folk medicine as
      analgesic and anti-inflammatory; however, several species of this genus are still
      poorly studied. Therefore, the aims of this study were to investigate the
      phytochemistry characterization by UPLC-DAD-QTOF-MS/MS, acute toxicity, anti
      inflammatory and antinociceptive properties of Miconia minutiflora (Bonpl.) DC.
      The methanol extract of M. minutiflora (Mm-MeOH) was subjected to ultra-high
      performance liquid chromatography (UPLC-DAD-QTOF-MS/MS) for the identification of
      the main phytocompounds. The anti-inflammatory properties of the extracts were
      studied using several inflammation models induced by carrageenan and acetic acid
      induced vascular permeability. Antinociceptive effects of Mm-MeOH were assessed
      in nociception induced by intraperitoneal acetic acid or subplantar formalin
      injection. The role of alpha-adrenergic, cholinergic, and opioid receptors in
      modulating the extract's antinociceptive activity was determined. Analyses by
      UPLC-DAD-QTOF-MS/MS revealed the presence of ellagic acid, gallotannin, and
      terpenes in the methanol extract. Mm-MeOH (100 mg/kg) reduced carrageenan-induced
      paw edema and vascular permeability and inhibited leukocyte migration toward the
      air pouch and pleural cavity. Furthermore, Mm-MeOH decreased tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels. Administration
      of Mm-MeOH reduced the number of writhes by 58.9% and increased the pain
      threshold in the formalin test. The anti-inflammatory action mechanism of Mm-MeOH
      is associated with inhibition of proinflammatory cytokines TNF-alpha and IL
      1beta, whereas the antinociceptive actions involve peripheral and central
      mechanisms with participation of alpha2-adrenergic receptors. These effects may
      be attributed to the presence of polyphenolics in the extract.

PMID- 30215113
TI  - ["Schuppenflechte" or "Psoriasis"? : Wording and awareness of technical terms in
      the general public].

PMID- 30215114
TI  - [Healthcare research in dermatology 2018 - power of the factual : What healthcare
      research is and who it serves].
AB  - In the dermatology practiced in Germany, healthcare research is an established
      and highly differentiated discipline. In many university dermatological
      institutions and private practices, studies are carried out on the processes of
      healthcare research for skin diseases. Commissioned by the German Society of
      Dermatology and the Professional Association of German Dermatologists, a
      significant number of the studies and projects are conducted by the German Center
      for Health Services Research in Dermatology (CVderm) as a nationwide reference
      center. Important projects include the implementation of patient registers and
      national care studies, research with secondary data and carrying out
      methodological studies for the further development of scientific questions.
      Important results are the national healthcare conferences for psoriasis, skin
      cancer, wounds and atopic dermatitis, the regional care networks as well as
      projects and cooperation with health insurance companies, local government and
      public institutions. In the interests of improved patient care, important factors
      of care are continuously improved. Future health services research in dermatology
      will be able to contribute even more efficiently for better care planning and
      management. Patient registers will facilitate the transfer of innovations into
      care and help to ensure that new treatment approaches can be implemented.
      Registers also support the optimization of therapy approaches, which can no
      longer be carried out on the basis of clinical studies alone, for example in the
      case of psoriasis, due to the large number of drugs available. In the era of
      digital medicine, healthcare research has an even more important function.

PMID- 30215115
TI  - Secular trends of hip fractures in France: impact of changing characteristics of
      the background population.
AB  - INTRODUCTION: Hip fractures are a societal burden because of their high morbidity
      and mortality and the cost they generate. With the aging of the population,
      worries grow about an increase of the incidence and incidence rate of hip
      fracture in the future. Controversial data have been provided in relation to the
      referencepopulation used. The aim of this study was to assess the impact of the
      choice of the reference population in the incidence rate of hip fracture.
      METHODS: Data were extracted from the French National Hospital Database related
      to the hospitalizations for hip fracture in France between 2002 and 2013 in
      patients over 59 years and were classified by gender and age (59-74, 75-84, over
      84 years, over 59 years). The crude incidence rates of hip fracture were
      calculated by dividing the number of hospitalizations for hip fracture by the
      corresponding populations. To assess the impact of the choice of the reference
      population, we then calculated the adjusted incidence rates using direct
      standardization on age for the 2013 reference population. RESULTS: From 2002 to
      2013, the incidence of hip fracture rose by 4.8% in women (from 49,287 to 51,661)
      and 21.8% in men (from 12,716 to 15,482) aged over 59 years. Meanwhile, French
      population over 59 years increased more with a rise of 21.3% in women and 28.7%
      in men, resulting in a decrease in the crude incidence rates of 13.6% in women
      and 5.4% in men. However, this decrease was larger after direct standardization
      on the 2013 population of reference as 25.6% in women and 19.2% in men as a
      result of a difference in age-structure of the population. CONCLUSIONS: The
      incidence of hip fractures continues to grow despite a reduced incidence rate
      throughout a 12-year-period.

PMID- 30215116
TI  - Neurological symptoms in Hypophosphatasia.
AB  - : Hypophosphatasia (HPP) typically manifests with fractures, tooth loss, and
      muscle pain. Although mental health diagnoses and neurological symptoms have not
      been previously well documented in HPP, they occur commonly. The recognition of
      non-traditional symptoms may improve patient satisfaction, preempt costly
      evaluation and misdiagnosis, and lead to further treatment options. INTRODUCTION:
      Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of
      tissue non-specific alkaline phosphatase (TNSALP). It is traditionally
      characterized by rickets in children and osteomalacia in adults, along with
      fractures, tooth loss, and muscle pain. Neurological symptoms and mental health
      diagnoses have not been widely reported, and we therefore report their prevalence
      in a cohort of patients with HPP. METHODS: A retrospective chart review was
      performed on a series of 82 HPP patients. Patient charts were reviewed to
      identify the possible presence and onset of 13 common neurological symptoms.
      RESULTS: Median age was 36 years (2 to 79). Seventeen had adult onset HPP (> 18
      years) and 65 had pediatric onset HPP (< 18 years). Median time from symptom
      onset to HPP diagnosis was 8 years (0 to 67). Seventy-four percent had a family
      history of bone disease, while 17% had a family history of neurologic disease.
      Bone problems occurred in 89%, dental problems in 77%, and muscle problems in
      66%. Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait
      change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in
      35%, and hearing loss in 33%. CONCLUSIONS: The extra-skeletal manifestations of
      HPP, specifically neurological symptoms, have not been previously well
      documented. However, mental health diagnoses and neurological symptoms such as
      headache and sleep disturbance occur commonly in patients with HPP. The
      recognition of non-traditional symptoms in HPP may improve patient satisfaction,
      preempt costly evaluation and misdiagnosis, and may lead to further treatment
      options.

PMID- 30215117
TI  - [Immunopathology of cutaneous drug eruptions].
AB  - BACKGROUND: Adverse drug reactions (ADR) are common and may present clinically
      and histologically in a very heterogeneous manner. The pathophysiological
      understanding about causal immunological and non-immunological events has
      developed significantly over the past years. Skin and mucosa are commonly
      affected and are prone for histopathological examination. Certain groups of drugs
      such as immune checkpoint inhibitors may cause specific adverse reactions.
      OBJECTIVES: To provide a comprehensive overview of the complex immunological
      events and the most common dermatohistopathological findings of cutaneous adverse
      drug reactions. MATERIAL AND METHODS: Review of the literature (PubMed), own
      study data and pictures obtained via routine diagnostics at the University of
      Bonn. RESULTS AND DISCUSSION: Drugs may induce a wide range of skin reactions
      displaying a diversity of cutaneous inflammatory patterns. Histopathological
      clues for drug eruptions may be: eosinophils, lichenoid infiltrate and isolated
      keratinocytic apoptosis; a thorough medical history and correlation of clinical
      findings and dermatohistopathology are most important. Knowledge of typical
      adverse reactions to checkpoint inhibitors and their management is of great
      clinical interest as their use is rising steadily.

PMID- 30215118
TI  - [Molecular predictors in immune oncology].
AB  - The current rapid development of novel therapeutic approaches in immune oncology
      (IO) and specifically in the field of immune checkpoint inhibition is accompanied
      by an equally dynamic development of novel biomarker approaches for the
      identification of responding/non-responding patients under IO treatment. In
      addition to the measurement of the expression of checkpoint ligands/receptors,
      complex molecular predictors are gaining increasing attention in certain IO
      treatment constellations. This includes the entity informed identification of
      molecularly defined biological tumor subtypes (e.g., microsatellite instable
      neoplasms), the measurement of tumor mutational load and immune cell effector
      signatures as relatively routine diagnostic compatible novel biomarker
      strategies. In addition, a multitude of even more complex molecular IO biomarker
      approaches is emerging. This development is accompanied by new patient selection
      strategies which are based on the simultaneous combinatorial evaluation of more
      than one parameter. This article provides a comprehensive overview on currently
      relevant aspects in the field of IO biomarkers.

PMID- 30215119
TI  - Peripheral nerve injuries in the pediatric population: a review of the
      literature. Part I: traumatic nerve injuries.
AB  - OBJECTIVE: This article reviews the clinical results that can be obtained after
      repair of a traumatic peripheral nerve injury in the pediatric population.
      METHODS: A systematic review of the published literature has been made. RESULTS:
      Functional outcome after major nerve injuries is sometimes disappointing in
      adults. However, children have been reported to experience much better functional
      results after nerve repair than adults. Moreover, recovery generally is faster in
      children. The superior capacity of children's central nervous system to adapt to
      external or internal environmental changes (neural plasticity) and the shorter
      recovery distance from the axon repair site to the target muscle are claimed to
      be crucial determinants of their favorable outcomes. Moreover, even in the
      pediatric population, it has been demonstrated that functional results are better
      the younger the patient is, including better clinical results in those injured in
      early childhood (< 6 years old) than in those injured in adolescence. Other
      favorable prognostic factors include the type of nerve injury (with complete
      transections doing less well than crush injuries) and the timing of surgery (with
      better outcomes after early repairs). CONCLUSIONS: All efforts should be done to
      repair in a timely and adequate fashion traumatic peripheral nerve injuries in
      children, as the results are good.

PMID- 30215120
TI  - Decompressive craniectomy in paediatric traumatic brain injury: a systematic
      review of current evidence.
AB  - INTRODUCTION: Paediatric traumatic brain injury (pTBI) is one of the most
      frequent neurological presentations encountered in emergency departments
      worldwide. Every year, more than 200,000 American children suffer pTBIs, many of
      which lead to long-term damage. OBJECTIVES: We aim to review the existing
      evidence on the efficacy of the decompressive craniectomy (DC) in controlling
      intracranial pressure (ICP) and improving long-term outcomes in children with
      pTBI. METHODS: A comprehensive search of the MEDLINE and EMBASE databases led to
      the screening of 212 studies, 12 of which satisfied inclusion criteria. Data
      extracted included the number and ages of patients, Glasgow Coma Scale scores at
      presentation, treatment protocols and short- and long-term outcomes. RESULTS:
      Each of the nine studies including ICP as an outcome reported that it was
      successfully controlled by DC. The 6-12 month outcome scores of patients
      undergoing DC were positive, or superior to those of medically treated groups in
      nine of 11 studies. Mortality was compared in only two studies, and was lower in
      the DC group in both.Very few studies are currently available investigating short
      and long-term outcomes in children with TBI undergoing DC. CONCLUSION: The
      currently available evidence may support a beneficial role of DC in controlling
      ICP and improving long-term outcomes.

PMID- 30215121
TI  - Embryonal tumor with multilayered rosettes: illustrative case and review of the
      literature.
AB  - BACKGROUND: Embryonal tumor with multilayered rosettes (ETMR) is a very rare
      entity and has seldom been reported. It has been newly defined tumor entity
      included in the latest update (revised fourth edition) of WHO 2016 Classification
      of Tumors of the Central Nervous System which portends a uniform dismal prognosis
      and survival even with the best of multimodality approaches. ILLUSTRATIVE CASE:
      This report documents the presentation of a 2-year-old girl with voluminous
      intracranial ETMR in the right parieto-occipital region. We describe clinical
      diagnosis, histological aspects, radiological features, and current management of
      this very aggressive tumor. CONCLUSION: Pediatric intracranial ETMR is a highly
      aggressive neoplasm, and it should be considered in the differential diagnosis of
      pediatric brain tumors.

PMID- 30215123
TI  - Fan Xia, Xiaojin Zhang, Xiaoding Lou, Quan Yuan (Eds.): Biosensors based on
      sandwich assays.

PMID- 30215124
TI  - Prasad L. Polavarapu (Ed.): Chiral analysis: advances in spectroscopy,
      chromatography, and emerging methods, 2nd ed.

PMID- 30215122
TI  - Protamine-gold nanoclusters as peroxidase mimics and the selective enhancement of
      their activity by mercury ions for highly sensitive colorimetric assay of Hg(II).
AB  - We certify that protamine-gold nanoclusters (PRT-AuNCs) synthesized by one-pot
      method exhibit peroxidase-like activity. The catalytic activity of PRT-AuNCs
      followed typical Michaelis-Menten kinetics and exhibited higher affinity to
      3,3',5,5'-tetramethylbenzidine (TMB) as the substrate compared to that of natural
      horseradish peroxidase. Meanwhile, we found that Hg(II) could dramatically and
      selectively enhance the peroxidase-like activity of PRT-AuNCs, and the enhanced
      mechanism by Hg(II) was demonstrated to be generation of the cationic Au species
      and the partly oxidized Au species (Audelta+) by Hg2+-Au0/Au+ interaction. Based
      on this finding, quantitative determinations of Hg(II) via visual observation and
      absorption spectra were achieved. The proposed strategy displays high selectivity
      that arises from the strong aurophilic interaction of mercury towards gold.
      Moreover, the developed method is highly sensitive with a wide linear range and
      low detection limit of 1.16 nM. This strategy is not only helpful to develop
      effective nanomaterials-based artificial enzyme mimics but also irradiative to
      discover new applications of artificial mimic enzymes in bio-detection, medical
      diagnostics, and biotechnology. Graphical abstract Protamine-gold nanoclusters
      (PRT-AuNCs) synthesized by one-pot method exhibit peroxidase-like activity.
      Hg(II) can stimulate the peroxidase-like activity of PRT-AuNCs selectively,
      enhancing their ability to catalyze the chromogenic reaction of TMB by H2O2.

PMID- 30215125
TI  - Sample preparation for mass spectrometry imaging of leaf tissues: a case study on
      analyte delocalization.
AB  - Appropriate sample preparation is pivotally important to obtain high-quality mass
      spectrometry imaging (MSI) data. Unlike mammalian tissues, preparation of
      cryosections from plant tissues for MSI measurement is quite challenging due to
      its intrinsic complex texture and cellular structure. This is especially true for
      leaf samples which are generally thin, water-rich, and fragile. In this work, a
      systematic study was performed, aiming to evaluate three embedding materials and
      five mounting approaches for matrix-assisted laser desorption ionization (MALDI)
      MSI of secondary metabolites in cross sections of the ginkgo leaf. Delocalization
      of endogenous metabolites was chosen as a major indicator for evaluation of three
      embedding materials including ice, carboxymethyl cellulose (CMC), and gelatin and
      different mounting approaches. Image distortion and analyte delocalization were
      observed when ice was used as an embedding medium. CMC embedding provided better
      results compared to the ice by using modified mounting approach. Among three
      embedding materials, no delocalization was observed in specimens embedded with
      gelatin, and gelatin embedding is the least affected by different mounting
      approaches. An alternative approach to mitigate analyte delocalization is the
      removal of embedding media embraced the tissue sections before mounting, which is
      particularly suitable for ice-embedded samples. Additionally, the extent of
      analyte delocalization was closely related to their lipophilicity/hydrophilicity
      properties, and less analyte diffusion was observed for hydrophobic analytes than
      for the water-soluble compounds.

PMID- 30215126
TI  - Sensitive determination of aldehyde metabolites in exhaled breath condensate
      using capillary electrophoresis with laser-induced fluorescence detection.
AB  - A novel capillary electrophoresis with laser-induced fluorescence detection
      method has been developed for the analysis of aldehyde metabolism biomarkers for
      oxidative stress in exhaled breath condensate (EBC), and fluorescein 5
      thiosemicarbazide was used as a derivatization reagent. In a simple capillary
      zone electrophoresis mode, ten low molecular weight aldehydes (LMWAs) could be
      well separated within 30 min. The reaction efficiency was doubled by increasing
      sample solution pH and magnetic stirring, and the LODs of this method reached
      0.16-3.4 nM (S/N = 3). Acceptable recoveries (82.1-115%) were obtained for EBC
      samples, and the RSD data were within 7.9%. This developed method has been
      applied for the analyses of EBC samples and evaluation of the correlation between
      smoking and the contents of aldehyde metabolites in EBC. Due to no need of buffer
      additives and sample preconcentration, this proposed method may provide an
      appealing alternative for the trace analyses of LMWAs in noninvasive biofluids.
      Graphical abstract ?.

PMID- 30215127
TI  - Rhizobacter gummiphilus NS21 has two rubber oxygenases (RoxA and RoxB) acting
      synergistically in rubber utilisation.
AB  - Biodegradation of poly(cis-1,4-isoprene) (rubber) by Gram-negative bacteria has
      been investigated on the enzymatic level only in Steroidobacter cummioxidans 35Y
      (previously Xanthomonas sp. 35Y). This species produces two kinds of rubber
      oxygenases, RoxA35Y and RoxB35Y, one of which (RoxB35Y) cleaves polyisoprene to a
      mixture of C20- and higher oligoisoprenoids while the other (RoxA35Y) cleaves
      polyisoprene and RoxB35Y-derived oligoisoprenoids to the C15-oligoisoprenoid 12
      oxo-4,8-dimethyltrideca-4,8-diene-1-al (ODTD). ODTD can be taken up by S.
      cummioxidans and used as a carbon source. Gram-positive rubber-degrading bacteria
      employ another type of rubber oxygenase, latex clearing protein (Lcp), for the
      initial oxidative attack of the polyisoprene molecule. In this contribution, we
      examined which type of rubber oxygenase is present in the only other well
      documented Gram-negative rubber-degrading species, Rhizobacter gummiphilus NS21.
      No homologue for an Lcp protein but homologues for a putative RoxA and a RoxB
      protein (the latter identical to a previously postulated LatA-denominated rubber
      cleaving enzyme) were identified in the genome of strain NS21. The roxANS21 and
      roxBNS21 genes were separately expressed in a ?roxA35Y/?roxB35Y background of S.
      cummioxidans 35Y and restored the ability of the mutant to produce
      oligoisoprenoids. The RoxANS21 and RoxBNS21 proteins were each purified and
      biochemically characterised. The results-in combination with in silico analysis
      of databases-indicate that Gram-negative rubber-degrading bacteria generally
      utilise two synergistically acting rubber oxygenases (RoxA/RoxB) for efficient
      cleavage of polyisoprene to ODTD.

PMID- 30215129
TI  - Secretory expression of beta-mannanase in Saccharomyces cerevisiae and its high
      efficiency for hydrolysis of mannans to mannooligosaccharides.
AB  - Degradation of mannans is a key process in the production of foods and
      prebiotics. beta-Mannanase is the key enzyme that hydrolyzes 1,4-beta-D
      mannosidic linkages in mannans. Heterogeneous expression of beta-mannanase in
      Pichia pastoris systems is widely used; however, Saccharomyces cerevisiae
      expression systems are more reliable and safer. We optimized beta-mannanase gene
      from Aspergillus sulphureus and expressed it in five S. cerevisiae strains.
      Haploid and diploid strains, and strains with constitutive promoter TEF1 or
      inducible promoter GAL1, were tested for enzyme expression in synthetic
      auxotrophic or complex medium. Highest efficiency expression was observed for
      haploid strain BY4741 integrated with beta-mannanase gene under constitutive
      promoter TEF1, cultured in complex medium. In fed-batch culture in a fermentor,
      enzyme activity reached ~ 24 U/mL after 36 h, and production efficiency reached
      16 U/mL/day. Optimal enzyme pH was 2.0-7.0, and optimal temperature was 60 
      degrees C. In studies of beta-mannanase kinetic parameters for two substrates,
      locust bean gum galactomannan (LBG) gave Km = 24.13 mg/mL and Vmax = 715 U/mg,
      while konjac glucomannan (KGM) gave Km = 33 mg/mL and Vmax = 625 U/mg. One-hour
      hydrolysis efficiency values were 57% for 1% LBG, 74% for 1% KGM, 39% for 10%
      LBG, and 53% for 10% KGM. HPLC analysis revealed that the major hydrolysis
      products were the oligosaccharides mannose, mannobiose, mannotriose,
      mannotetraose, mannopentaose, and mannohexaose. Our findings show that this beta
      mannanase has high efficiency for hydrolysis of mannans to mannooligosaccharides,
      a type of prebiotic, suggesting strong potential application in food industries.

PMID- 30215130
TI  - [Oxytocin in schizophrenia : Evidence for an etiological and therapeutic
      relevance of the social neuromodulator].
AB  - Neurobiological results from animal models as well as biochemical and genetic
      findings in patients indicate that the oxytocin (OT) system may be dysfunctional
      in schizophrenia. On this pathogenetic basis transnasally administered OT (tnOT)
      could be an innovative treatment option for schizophrenia. Experimental data from
      animal studies are also suggestive of a particular effectiveness in treatment
      resistant schizophrenia. To date, clinical data on tnOT treatment of
      schizophrenia patients does not unequivocally support a general therapeutic
      effect on the psychopathology but suggests positive effects on higher integrated
      social cognitive performance, such as empathy and mentalization. In particular,
      tnOT augmentation of a social cognitive skills training resulted in a marked and
      lasting treatment effect; however, numerous person- and context-dependent
      variables can potentially moderate individual effects of OT and may even reverse
      effects in certain constellations. Most clinical studies so far have not
      systematically accounted and controlled for these factors with the probable
      result of larger variance of recorded treatment effects and lower likelihood of
      ascertaining positive effectiveness. Furthermore, there is still a gap of
      knowledge on dose response relations and central nervous system (CNS) permeation
      in man following tnOT administration. This review aims to give a concise overview
      on the evidence for the etiological relevance of the neurohormone OT and its
      treatment potential in schizophrenia.

PMID- 30215131
TI  - [Aceruloplasminemia : Diagnosis and treatment of a rare disease].

PMID- 30215128
TI  - The scale-up cultivation of Candida utilis in waste potato juice water with
      glycerol affects biomass and beta(1,3)/(1,6)-glucan characteristic and yield.
AB  - New ideas on production of yeast origin beta-glucan preparations for industrial
      application are attracting interest considering market development of that high
      value functional polysaccharide. Sellecting an efficient yeast producer and
      designing culture conditions are a prerequisite for obtaining high yield of beta
      glucan. The aim of this study was to describe at the first time the influence of
      the mode of cultivation (shake-flasks and batch fermentation) and time of culture
      on characteristic and yield of biomass and beta(1,3)/(1,6)-glucan preparations of
      Candida utilis ATCC 9950 after cultivation in medium based on waste potato juice
      water supplemented with 10% of glycerol. After shake-flask culture, the biomass
      was characterized by higher protein content (app. 26.5%) compared to 19% after
      batch fermentation while the cultivation on a biofermentor scale promoted
      polysaccharides biosynthesis. The highest output of purified beta(1,3)/(1,6)
      glucan preparation (5.3 gd.w./L), containing app. 85% of that polysaccharide, was
      found after 48 h cultivation in biofermentor. Batch fermentation promoted
      biosynthesis of alkali-insoluble beta(1,3)/(1,6)-glucan fraction, decreasing the
      content of beta(1,6)-glucan. The yield of beta(1,3)/(1,6)-glucan synthesis was
      0.063 (g/g glycerol), while the productivity of that polysaccharide reached 0.094
      (g/L/h). Longer batch fermentation (72 h) resulted in reduction of production
      efficiency of beta-glucan preparation under studied conditions. The results of
      the study provide a new efficient biotechnological solution to produce high-value
      beta-glucan preparations of C. utilis origin based on valorization of agro-waste
      potato juice water with glycerol.

PMID- 30215132
TI  - [Neuroimmunology and rheumatology: overlap and differential diagnoses].
AB  - Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are
      chronic inflammatory diseases of the central nervous system (CNS). They may cause
      inflammation in the brain, spinal cord and optic nerve. Both conditions must be
      differentiated from CNS manifestations of other systemic autoimmune diseases such
      as systemic lupus erythematosus (SLE), Sjogren's syndrome, autoinflammtory
      diseases and sarcoidosis, since amongst others myelitis and optic nerve
      inflammation may also occur in these conditions. Nevertheless, coexistence of MS
      or NMOSD with rheumatic disorders such as SLE or Sjogren's syndrome has also been
      reported especially in NMOSD. Since the therapeutic approach is different it is
      important to determine a clear diagnosis. In addition some drugs used in
      rheumatic disease such as anti-tumor necrosis factor biologics may induce
      inflammatory disease of the CNS and should be avoided in MS. An interdisciplinary
      approach between neuroimmunology and rheumatology is important for optimal care
      and treatment in such patients.

PMID- 30215134
TI  - [Frequency of coercive measures as a quality indicator for psychiatric
      hospitals?]
AB  - BACKGROUND: The percentage of patients subjected to coercive measures has been
      proposed as 1 of 10 quality indicators for psychiatric inpatient treatment by the
      German Association of Psychiatry, Psychotherapy and Psychosomatics (DGPPN).
      Internationally, there are similar recommendations and corresponding reporting
      systems. METHODS: The registry of coercive measures of psychiatric hospitals in
      Baden-Wurttemberg that was established in 2015, yields the possibility to examine
      the appropriateness of this indicator, based on raw data of 108,863 cases in
      2016. This study investigated how the indicator is influenced by patient
      variables and characteristics of hospital structure. RESULTS: The percentage of
      cases exposed to coercive measures was strongly (r = 0.6) correlated with the
      percentage of involuntarily treated cases. With respect to the latter, hospitals
      varied widely with a range from 0.7% up to 24.1%. Specialized wards serving
      patients outside the catchment area with a high number of coercive measures also
      had a strong influence on the results of a benchmarking comparison. CONCLUSION:
      The indicator is a good instrument for longitudinal evaluation of an institution;
      however, due to a high number of known and unknown confounding factors, it is
      inappropriate for the purpose of comparing psychiatric hospitals.

PMID- 30215133
TI  - [Intracranial vascular malformations].
AB  - Intracranial vascular malformations range from incidental asymptomatic vascular
      alterations up to life-threatening vascular disorders. Arteriovenous
      malformations and dural arteriovenous fistulas are cerebral vascular
      malformations with arteriovenous shunting of blood. In the majority of cases they
      are accompanied by an elevated risk of intracerebral hemorrhage and can cause
      severe symptoms. They can be treated conservatively or interventionally via
      microneurosurgery, endovascular embolization and radiation therapy. Cavernous
      malformations, developmental venous anomalies (DVA) and capillary telangiectasia
      are cerebral vascular malformations without arteriovenous shunting. Cavernous
      malformations are rarely symptomatic in the form of cerebral hemorrhage, headache
      or seizures and in such cases an operative treatment can be indicated. The DVA
      and capillary telangiectasia are usually asymptomatic and do not require
      treatment.

PMID- 30215135
TI  - [A selective review of recent research results in biological psychiatry].
AB  - In accordance with the motto of this year's German Society for Psychiatry,
      Psychotherapy and Psychosomatics (DGPPN) conference, this article surveys very
      recent developments in biological psychiatry and neurosciences that have the
      potential to open up new vistas for the psychiatry and psychotherapy of the
      future. The work reported includes progress in genome-wide association studies,
      the implications of these findings for psychiatric nosology and gene-environment
      interactions, new methods to characterize mechanisms of altered brain function in
      animal models and humans and the translation of these findings into new
      therapies. As a core methodology for the psychiatry of the future, biological and
      applied neuroscience approaches should benefit from sustained structural funding
      to ensure that these advances impact real-world patient care.

PMID- 30215136
TI  - Presence of trichomonads in subgingival biofilm of patients with periodontitis:
      preliminary results.
AB  - This study aims to evaluate the prevalence of trichomonads in the subgingival
      biofilm of patients with periodontitis. Secondarily, the trichomonad presence was
      related to patient characteristics and periodontal clinical parameters, in order
      to highlight the factor favoring the development of these protozoans. Subgingival
      biofilm samples were collected from at least two diseased and one healthy site in
      50 patients suffering from periodontitis. Trichomonads were identified using
      phase contrast microscopy. All patient characteristics and periodontal clinical
      parameter data were then statistically analyzed. From the 50 patients examined,
      195 sites were sampled, including 145 diseased ones. Trichomonads were only
      observed on 16 of the 145 diseased sites (11%) and none in the other 50 healthy
      sites. Based on these results, 20% (n = 10) of patients were positive for the
      presence of trichomonads from at least one of the diseased sites collected. Tooth
      mobility, substantial supra-gingival dental deposits, and severe clinical
      attachment loss were statistically associated with trichomonad presence. If the
      subgingival biofilm of male patients over the age of 50 seemed to be more
      frequently contaminated with trichomonads, this data was not statistically
      supported. This preliminary study indicates for the first time that in
      periodontitis-involved patients, trichomonads are observed in the subgingival
      biofilm collected from diseased sites with severe bone loss, but not from healthy
      teeth. Further investigations are needed to fully explore the role of this
      microorganism in the etiology of periodontal disease.

PMID- 30215137
TI  - First molecular identification of Buxtonella ciliates from captive-bred mangabeys
      (Cercocebus torquatus) from China.
AB  - Buxtonella species are large cyst-forming ciliates that infect ruminants and
      monkeys, and are morphologically similar to Balantidium coli ciliates that infect
      pigs, humans, monkeys, and other animals. In this study, we isolated spherical
      cysts of ciliates that were similar to those of Balantidium and Buxtonella
      species within collared mangabeys (Cercocebus torquatus) from the Wangcheng Zoo
      of Luoyang in the Henan Province of central China. The cysts were further
      identified and designated as belonging to the Buxtonella monkey genotype based on
      molecular analyses of 18S rRNA, 5.8S rRNA, and ITS1-5.8S rRNA-ITS2 genetic
      markers. To our knowledge, this is the first report of Buxtonella monkey genotype
      within monkeys in China. These results will help clarify the classification of
      species of cyst-forming ciliate infections in monkeys.

PMID- 30215138
TI  - A gel-free proteomic analysis of Taenia solium and Taenia crassiceps cysticerci
      vesicular extracts.
AB  - The taeniasis/cysticercosis complex is a zoonosis caused by the presence of the
      parasite Taenia solium in humans. It is considered a neglected disease that
      causes serious public health and economic problems in developing countries. In
      humans, the most common locations for the larval form are the skeletal muscles,
      ocular system, and the central nervous system, which is the most clinically
      important. Several glycoproteins of T. solium and Taenia crassiceps cysticerci
      have been characterized and studied for their use in the immunodiagnosis of
      neurocysticercosis and/or the development of synthetic or recombinant vaccines
      against cysticercosis. The aim of this study was to perform a gel-free shotgun
      proteomic analysis to identify saline vesicular extract (SVE) proteins of T.
      solium and T. crassiceps cysticerci. After solubilization of the SVE with and
      without surfactant reagent and in-solution digestion, the proteins were analyzed
      by LC-MS/MS. Use of a surfactant resulted in a significantly higher number of
      proteins that were able to be identified by LC-MS/MS. Novel proteins were
      identified in T. solium and T. crassiceps SVE. The qualitative analysis revealed
      a total of 79 proteins in the Taenia species: 29 in T. solium alone, 11 in T.
      crassiceps alone, and 39 in both. These results are an important contribution to
      support future investigations and for establishing a Taenia proteomic profile to
      study candidate biomarkers involved in the diagnosis or pathogenesis of
      neurocysticercosis.

PMID- 30215139
TI  - Agents of swimmer's itch-dangerous minority in the Digenea invasion of Lymnaeidae
      in water bodies and the first report of Trichobilharzia regenti in Poland.
AB  - Trichobilharzia spp. have been identified as a causative agent of swimmers' itch,
      a skin disease provoked by contact with these digenean trematodes in water. These
      parasites have developed a number of strategies to invade vertebrates. Since we
      have little understanding of the behavior of these parasites inside the human
      body, the monitoring of their invasion in snail host populations is highly
      recommended. In our research, lymnaeid snails were collected from several Polish
      lakes for two vegetation seasons. The prevalence of bird schistosomes in snail
      host populations was significantly lower than that of other digenean species. We
      were the first to detect the presence of the snails emitted Trichobilharzia
      regenti (potentially the most dangerous nasal schistosome) in Poland. In
      addition, by sequencing partial rDNA genes, we confirmed the presence of the
      snails positive with Trichobilharzia szidati in Polish water bodies, showing that
      swimmer's itch is more frequent during summer months and that large snails are
      more often infected with bird schistosomes than small ones.

PMID- 30215140
TI  - Recurrent Urinary Tract Infections in Females and the Overlap with Overactive
      Bladder.
AB  - PURPOSE OF REVIEW: There are an estimated 33 million men and women with
      overactive bladder (OAB) in the USA. Despite the prevalence of OAB, it remains a
      frequently misdiagnosed condition. OAB has shared symptomatology with other
      common urologic conditions, namely recurrent urinary tract infections (UTIs).
      Here, we will review key distinguishing features of OAB that aid in establishing
      an accurate diagnosis and recent advances in OAB management. RECENT FINDINGS:
      Recent studies have shown that among women presenting with lower urinary tract
      symptoms, the majority were diagnosed with UTIs and treated without performing a
      urine culture as routine care. The authors found that when urine cultures were
      obtained, less than half of women had a positive urine culture, suggesting that
      empiric treatment of UTIs without cultures commonly led to a misdiagnosis of UTI.
      The symptoms of OAB have overlap with other common conditions, most notably UTI,
      BPH, and bladder cancer/carcinoma in situ. Despite the shared symptomatology of
      OAB and UTI, the timing of symptom onset is usually very different between the
      two. UTI symptoms are generally acute, whereas those of OAB are generally
      chronic. OAB and UTI share the common features of urgency, frequency, and
      nocturia. However, dysuria and hematuria are not features of OAB, while they are
      frequently seen in UTI. Of note, urgency, frequency, and nocturia are rarely seen
      in bladder cancer/carcinoma in situ; when these symptoms do occur, it is
      generally in the setting of microhematuria. One study of patients with carcinoma
      in situ found that 41% had macroscopic hematuria and 44% had microscopic
      hematuria at presentation. In patients with lower urinary tract symptoms, it is
      important to perform a urinalysis (UA) to evaluate for microhematuria to rule out
      the possibility of malignancy. First-line treatment of OAB (outside the setting
      of UTI) involves behavioral modification, including bladder training, fluid
      management, and pelvic floor exercises. Numerous studies have supported
      behavioral modification strategies as the most efficacious initial step in
      treatment. Although routinely given for recurrent UTIs and vaginal atrophy in
      postmenopausal women, several review articles have shown that vaginal estrogen is
      an effective treatment of lower urinary tract symptoms. The importance of
      distinguishing OAB from other conditions presenting with similar symptoms is key
      in preventing misdiagnosis, treatment delays, and antibiotic overuse. Here, we
      have reviewed key parameters distinguishing OAB from UTI, the most commonly
      misdiagnosed condition among those presenting with lower urinary tract symptoms
      (LUTS). Given that UTI is the most commonly misdiagnosed condition among women
      with OAB, we recommend relying on urine cultures and the constellation of acute
      onset dysuria, frequency, and urgency as more important diagnostic factors in
      distinguishing these conditions.

PMID- 30215141
TI  - Characterization of sub-watershed-scale stream chemistry regimes in an
      Appalachian mixed-land-use watershed.
AB  - An exploratory study was conducted in an urbanizing, mixed-land-use Appalachian
      watershed. Six study sites, characterized by contrasting land use/land cover,
      were instrumented to continuously monitor stream stage. Weekly grab samples were
      collected from each site and analyzed for elemental composition via spectrometric
      and spectrophotometric methods. Additional physico-chemical parameters were
      measured in situ. Data were analyzed using a suite of statistical methods,
      including hypothesis testing, correlation analysis, and principal components
      analysis (PCA). Significant differences (p < 0.05) between study sites were
      identified for every measured parameter except Co, Cu, Pb, and Ti concentrations.
      However, different parameters showed significant differences (p < 0.05) between
      site pairings. PCA results highlight consistent spatial differences between
      elemental composition and physico-chemical characteristics of streamwater
      samples. Results from correlation analyses indicated varying significant (p <
      0.05) relationships between chemical parameters and hydroclimate metrics, with
      certain elements (e.g., Ca and Sr) and physico-chemical parameters (e.g.,
      specific conductance) displaying greater sensitivity to hydroclimate at mixed
      land-use sites, as compared to predominately urban, agricultural, or forest
      sites. Given the geological, topographical, and climatological similarities
      between the sites, and their close proximity, it was concluded that land use
      characteristics and associated hydrologic regime contrasts were the primary
      factors contributing to the observed results. Results comprise valuable
      information for land and water managers seeking to mitigate the impacts of land
      use practices on water resources and aquatic ecosystem health. The applied
      methodology can be used to more effectively target sub-watershed-scale
      remediation/restoration efforts within mixed-use watersheds, thereby improving
      the ultimate efficacy of management practices.

PMID- 30215142
TI  - Illness perceptions are associated with higher health care use in survivors of
      endometrial cancer-a study from the population-based PROFILES registry.
AB  - OBJECTIVES: According to the Common Sense Model of self-regulation, cancer
      survivors construct perceptions of their illness as a (mal)adaptive mechanism.
      These perceptions might impact on health care use. We aimed to explore the
      association between illness perceptions and health care use in stage I-II
      endometrial cancer (EC) survivors, and whether these associations differed by
      time since diagnosis. METHODS: A survey was conducted in 2008 by the population
      based PROFILES registry among EC survivors diagnosed between 1999 and 2007.
      Survivors (n = 742, 77% response) completed the Brief Illness Perception
      Questionnaire (BIPQ) and questions on health care use in the past 12 months.
      Clinical data were accessed from the Netherlands Cancer Registry. Multiple
      logistic regression was used to evaluate the relationship between illness
      perceptions and health care use. RESULTS: Between 15 and 22% of the survivors had
      negative illness perceptions. Survivors with more negative perceptions on
      consequences, timeline, treatment control, identity, cognitive representation,
      concern, emotion, and emotional representation were more likely to make >= 1
      visit to their family physician/general practitioner in relation to their cancer
      when compared with survivors with more positive illness perceptions. More
      negative perceptions on consequences, timeline, identity, and concern were
      associated with >= 2 general or cancer-related visits to the medical specialists.
      The association between negative illness perceptions and health care use was more
      prominent among long-term (>5 years post-diagnosis) EC survivors. CONCLUSIONS:
      Negative illness perceptions among EC survivors were associated with higher
      health care use. For individuals with maladaptive illness perceptions, visits to
      their health care provider may reduce worry about their illness. Future research
      might address the effects of intervening in maladaptive illness perceptions on
      use of health care in this category of survivors.

PMID- 30215144
TI  - Correction to: Diabetes, Renal, and Cardiovascular Disease in p47phox-/- Chronic
      Granulomatous Disease.

PMID- 30215143
TI  - A Privacy Preservation Secure Cross Layer Protocol Design for IoT Based Wireless
      Body Area Networks Using ECDSA Framework.
AB  - Internet of Things (IoT) provides the collection of devices in different
      applications in which Wireless Body Area Network (WBAN) is placed an crucial
      role. The WBAN is a wireless sensor network consisting of sensor nodes that is
      collected from IoT which is implanted in the human body to remotely monitor the
      patient's physiological signals without affecting their routine work. During
      emergency situations or life-threatening situations there is a need for a better
      performance to deliver the actual data with an efficient transmission and there
      is still a challenge in efficient remote monitoring. So, in this paper an
      application for cross layer protocol design architecture of Elliptic Curve
      Digital Signature Algorithm (ECDSA) has been proposed. It replaces the protocol
      architecture of WBAN (IEEE 802.15.6), WMAN (IEEE 802.16), and 3G, WLAN (IEEE
      802.11) or wired networks. The lightweight secure system provides secure data
      transmission and access control mechanisms by using ECDA-based proxy signature
      algorithm. The efficiency of the system is implemented using simulation models
      that were developed using NS-2, and the results obtained shows an optimum
      solution in terms of delay, PDR, throughput, jitter, packet transmission time,
      dropping ratio and packet delivery. The viability of the methodology proposed is
      illustrated by the response.

PMID- 30215145
TI  - Design, Synthesis, Photophysical Properties, Biological Estimation and Molecular
      Docking Studies of Novel Schiff Base Derivatives as Potential Urease Inhibitors.
AB  - A quinoline functionalized two novel fluorescent Schiff bases, N-(quinolin-2
      ylmethylene) anthracen-1-amine (SB1) and 2-(quinolin-2-ylmethyleneamino) benzene
      thiol (SB2) were synthesized and confirmed by using 1H NMR, IR and GC-MS
      techniques. The spectroscopic properties were examined by absorption spectroscopy
      and fluorescence spectroscopy. The absorption and fluorescence spectra of the
      probes (SB1 and SB2) were measured in a variety of solvents. Both the compounds
      were tested for urease inhibitory activity. The synthesized compound SB2 proved
      to be the most effective screening for enzyme inhibitory activity with IC50 =
      0.111 MUM than SB1 (IC50 = 0.287 MUM). Molecular docking studies were performed
      to delineate the binding affinity and conformational positions of chemical
      compounds within the active region of the target protein. In-vitro analysis
      depicts the potency of SB1 in free radical scavenging as compared to the
      reference drug vitamin C.

PMID- 30215147
TI  - Efficacy of a thermally treated single file compared with rotary systems in
      endodontic retreatment of curved canals: a micro-CT study.
AB  - OBJECTIVES: This study aimed to compare WaveOne Gold with ProTaper and RaCe
      systems regarding remaining filling material, apical transportation (AT), and
      working time (WT) after (i) filling removal and (ii) shaping of curved canals.
      METHODS: Thirty mesiobuccal canals of maxillary molars were prepared and filled.
      After 30 days, they were randomly assigned into three groups (n = 10), according
      to the instruments used for filling removal and shaping, respectively: WOG
      WaveOne Gold Primary and Medium; PTG-ProTaper Retreatment and ProTaper Next; RCG
      D-RaCe and RaCe. Micro-CT analysis assessed the residual filling material and AT.
      WT was recorded. Data were statistically analyzed (alpha = .05). RESULTS: There
      was no significant difference between groups in the amount of filling material at
      any evaluated moment (P > .05). All groups presented low AT values. The WT was
      similar in all groups in filling removal (P > .05), and in shaping step WOG was
      faster than PTG and RCG (P < .05). CONCLUSIONS: Neither system could completely
      remove the filling material. The instruments evaluated were safe and the
      reciprocating system was faster than the rotary systems in shaping the canals.
      CLINICAL RELEVANCE: This study provided consistent information on filling
      material removal capacity of WaveOne Gold. Considering that all tested systems
      were safe, WaveOne Gold may be an alternative with cost-effectiveness and shorter
      learning curve for endodontic retreatment.

PMID- 30215146
TI  - Drug-Polymer Interaction, Pharmacokinetics and Antitumor Effect of PEG-PLA/Taxane
      Derivative TM-2 Micelles for Intravenous Drug Delivery.
AB  - PURPOSE: A novel polymer micelle was prepared with a high drug loading, good
      stability, high tolerance and better anti-tumor effect. METHODS: TM-2 was
      encapsulated in poly-block-poly (D, L-lactic acid) self-assembled micelles by the
      thin-film hydration method. From the critical micelle concentrations of the
      copolymers, particle size, drug loading and encapsulation efficiency of drug
      loading micelles, the appropriate polymer material could be assessed. Comparisons
      between TM-2 solution and TM-2 micelles were done to evaluate the
      pharmacokinetics and toxicity in rats, compared with Taxol to evaluate the anti
      tumor effect in mice. RESULTS: The optimized TM-2 micelles achieved a high drug
      loading (~20%) with the polymer material of PEG2k-PLA2.5k, with a particle size
      of 30 nm and no significant change in particle size after lyophilization. The
      result of pharmacokinetic experiment displayed that the half-life in vivo was
      obviously prolonged. The maximum tolerated dose of TM-2 micelles was
      approximately 25 mg/kg in rats, and the relative tumor growth rate of Taxol (15
      mg/kg), TM-2 (10 mg/kg), TM-2 (15 mg/kg) and TM-2 (40 mg/kg) in mice were 49.35%,
      49.14%, 36.44 and 9.98% respectively. CONCLUSIONS: TM-2 micelles with high drug
      loading increased drug solubility, improved tolerance, antitumor effects and
      reduced toxicity.

PMID- 30215148
TI  - Impulse Noise Removal from Medical Images by Two Stage Quaternion Vector Median
      Filter.
AB  - This paper presents a two-stage impulse noise removal filter from medical images.
      Quaternion is used to represent differences of two pixels. The pixels are sorted
      and assigned a rank based on the aggregated sum of pixel differences with other
      pixels inside the filtering window. The central pixel is considered as corrupted
      by an impulse if its rank is bigger than a predefined rank and the minimum
      difference between it and other pixels in the four edge direction inside the
      window is larger than a predefined threshold. The noisy pixel is replaced by
      output of vector median filter implemented using quaternion. For color images,
      both intensity and chromaticity components are used. Quaternion processes color
      images as single unit rather than as separated color channels. This preserves the
      correlation and three dimensional vector natures of the color channels. For
      grayscale medical images, the same algorithm is implemented by using the
      intensity difference between two pixels. Experimental results show improved
      performance of the proposed filter in suppressing the impulse noise while
      retaining the original image details comparing against other well-known filters.

PMID- 30215150
TI  - Effect of providing drug utilization review information on tricyclic
      antidepressant prescription in the elderly.
AB  - Tricyclic antidepressants are known as potentially inappropriate medications in
      the elderly. A notification issued in July 2015 in South Korea recommended
      caution while prescribing tricyclic antidepressants to the elderly. Further,
      since October 2015, the nationwide computerized drug utilization review
      monitoring system provides a pop-up window, on a real-time basis, whenever
      tricyclic antidepressants are prescribed to elderly outpatients. Therefore, we
      evaluated whether providing drug utilization review information was effective in
      reducing tricyclic antidepressant prescription to elderly outpatients. We used
      the Health Insurance Review and Assessment Service-Adult Patient Sample data from
      2014 to 2016. Data related to the prescription of tricyclic antidepressants to
      outpatients aged 65 years or more were extracted. We determined the number of
      prescriptions per day per 100,000 elderly patients in each month, compared the
      average number of prescriptions before and after the drug utilization review
      information was provided, and evaluated the changes in the number of
      prescriptions by using an interrupted time series analysis. The average number of
      tricyclic antidepressant prescriptions per day per 100,000 elderly patients
      decreased from 76.6 (75.5 to 77.6) to 65.7 (64.5 to 66.9), a 14.2% reduction
      after the provision of drug utilization review information started. Following
      initiation of provision of drug utilization review information, there was an
      immediate drop of 9.2 tricyclic antidepressant prescriptions per day per 100,000
      elderly patients, whereas there was no statistically significant change in
      trends. Providing the drug utilization review information on tricyclic
      antidepressant prescription for the elderly contributed to the reduction in
      tricyclic antidepressant prescriptions.

PMID- 30215151
TI  - Deafferentation-induced alterations in mitral cell dendritic morphology in the
      adult zebrafish olfactory bulb.
AB  - The removal of afferent input to the olfactory bulb by both cautery and chemical
      olfactory organ ablation in adult zebrafish results in a significant decrease in
      volume of the ipsilateral olfactory bulb. To examine the effects of
      deafferentation at a cellular level, primary output neurons of the olfactory
      bulb, the mitral cells, were investigated using retrograde tract tracing with
      fluorescent dextran using ex vivo brain cultures. Morphological characteristics
      including the number of major dendritic branches, total length of dendritic
      branches, area of the dendritic arbor, overall dendritic complexity, and optical
      density of the arbor were used to determine the effects of deafferentation on
      mitral cell dendrites. Following 8 weeks of permanent deafferentation there were
      significant reductions in the total length of dendritic branches, the area of the
      dendritic arbor, and the density of fine processes in the dendritic tuft. With 8
      weeks of chronic, partial deafferentation there were significant reductions in
      all parameters examined, including a modified Sholl analysis that showed
      significant decreases in overall dendritic complexity. These results show the
      plasticity of mitral cell dendritic structures in the adult brain and provide
      information about the response of these output neurons following the loss of
      sensory input in this key model system.

PMID- 30215149
TI  - Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?
AB  - PURPOSE OF REVIEW: In the last decade many studies have suggested an association
      between the altered gut microbiota and multiple systemic diseases including
      diabetes. In this review, we will discuss potential pathophysiological
      mechanisms, the latest findings regarding the mechanisms linking gut dysbiosis
      and type 2 diabetes (T2D), and the results obtained with experimental modulation
      of microbiota. RECENT FINDINGS: In T2D, gut dysbiosis contributes to onset and
      maintenance of insulin resistance. Different strategies that reduce dysbiosis can
      improve glycemic control. Evidence in animals and humans reveals differences
      between the gut microbial composition in healthy individuals and those with T2D.
      Changes in the intestinal ecosystem could cause inflammation, alter intestinal
      permeability, and modulate metabolism of bile acids, short-chain fatty acids and
      metabolites that act synergistically on metabolic regulation systems contributing
      to insulin resistance. Interventions that restore equilibrium in the gut appear
      to have beneficial effects and improve glycemic control. Future research should
      examine in detail and in larger studies other possible pathophysiological
      mechanisms to identify specific pathways modulated by microbiota modulation and
      identify new potential therapeutic targets.

PMID- 30215152
TI  - Theoretical design of metal-phthalocyanine dye-sensitized solar cells with
      improved efficiency.
AB  - The present work carried out a theoretical study of the electronic structures,
      absorption spectra, and photovoltaic performance of two series of transition
      metal-phthalocyanine derived from nonperipheral electron-donating substituents,
      either (2-phenyl) phenoxy(M-PC1) or quinoleinoxy(M-PC2). The DFT and TD-DFT were
      employed for this study. The effect of modifying the central metal atoms and the
      substitution on cell performance were investigated in terms of polarizability
      (alpha), hyper-polarizability (beta), chemical potential (MU), chemical hardness
      (eta), electrophilicity power (omega), FMOs, energy gaps, UV/vis absorption
      spectra and injected driving force (DeltaGinject), light harvesting efficiencies
      (LHE), total reorganization energy (lambdatot), open circuit photovoltage (Voc),
      and life time of the excited state (tau). The results obtained by using these
      parameters showed that the replacement of (2-phenyl) phenoxy by a proposed
      substituent such as quinoleinoxy would increase the hyper-polarizability, light
      harvesting efficiency, and open circuit photovoltage, while on the other hand the
      reorganization energy and the injection driving force are decreased. Modifying
      central metal atoms, such as Zn, Cd, Pd, and Pt, exhibited good performance in
      terms of the driving force of electron injection, charge transfer
      characteristics, and dye reorganization as compared with the Cu reference dye.
      The findings provided a useful prediction and perspective for the promising
      future for high-efficiency dye-sensitized solar cells (DSSCs) with dyes based on
      phthalocyanine. Graphical abstract Photovoltaic performance of Metallo
      phthalocyanine contening (2-phenyl) phenoxy and quinoleinoxy.

PMID- 30215153
TI  - Skin Sodium and Hypertension: a Paradigm Shift?
AB  - PURPOSE OF REVIEW: Dietary sodium is an important trigger for hypertension and
      humans show a heterogeneous blood pressure response to salt intake. The precise
      mechanisms for this have not been fully explained although renal sodium handling
      has traditionally been considered to play a central role. RECENT FINDINGS: Animal
      studies have shown that dietary salt loading results in non-osmotic sodium
      accumulation via glycosaminoglycans and lymphangiogenesis in skin mediated by
      vascular endothelial growth factor-C, both processes attenuating the rise in BP.
      Studies in humans have shown that skin could be a buffer for sodium and that skin
      sodium could be a marker of hypertension and salt sensitivity. Skin sodium
      storage could represent an additional system influencing the response to salt
      load and blood pressure in humans.

PMID- 30215155
TI  - A case of facioscapulohumeral muscular dystrophy and myasthenia gravis with
      positivity of anti-Ach receptor antibody: a fortuitous association?

PMID- 30215154
TI  - Sonication-assisted preparation of a nanocomposite consisting of reduced graphene
      oxide and CdSe quantum dots, and its application to simultaneous voltammetric
      determination of ascorbic acid, dopamine and uric acid.
AB  - Cadmium selenide quantum dots were capped with reduced graphene oxide that was
      modified with thioglycolic acid. The nanocomposite was prepared by 5-min
      sonication of a solution of graphene oxide, thioglycolic acid, and cadmium(II)
      nitrate and selenium powder in the presence of NaBH4. X-ray diffraction and
      transmission electron microscopy were used to characterize the nanocomposite. A
      glassy carbon electrode (GCE) was modified with this nanocomposite and used for
      simultaneous determination of dopamine (DA), ascorbic acid (A) and uric acid
      (UA). The modified GCE was characterized by using cyclic voltammetry and
      differential pulse voltammetry. Simultaneous determination of AA, DA and UA was
      accomplished at working voltages of -50, +148 and + 280 mV (all vs. Ag/AgCl),
      respectively. The voltammetric response to DA is linear in the 4.9 to 74.0 MUM
      concentration range, and the detection limit (defined as 3sigma of the blank) is
      0.11 MUM. The respective data are 0.39-1.0 mM and 66 MUM for AA, and 9.0 to 120.0
      MUM and 0.12 MUM for UA. The electrode was successfully applied to the
      determination of the 3 species in spiked urine samples. Graphical abstract
      Graphical abstract contains poor quality of text in image. Otherwise, please
      provide replacement figure file.Thank you for your comment. New garaphical
      abstract was attached. A sonochemical method was applied for synthesizing reduced
      graphene oxide decorated thioglycolic acid capped cadmium selenide quantum dots.
      A modified glassy carbon electrode was prepared for simultaneous determination of
      ascorbic acid, dopamine and uric acid.

PMID- 30215156
TI  - First-time complete visualization of a preserved meningeal artery in the mummy of
      Nakht-ta-Netjeret (ca. 950 BC).
AB  - The preservation of the meningeal artery in ancient mummified bodies,
      particularly in anthropogenic Egyptian mummies, is a highly controversial topic
      in neuroscience and anthropological research. A recent (2015) debate between Wade
      and Isidro, based on the interpretation of the meningeal grooves and cast in a
      skull from the necropolis of Kom al-Ahmar Sharuna (Egypt), highlighted both the
      necessity of having clear radiological descriptions of this anatomical structure
      and of assessing large collections of mummified crania. Here, we present for the
      first time an instance of extremely well-preserved middle meningeal artery in the
      mummy of the ancient Egyptian dignitary Nakht-ta-Netjeret (ca. 950 BC), still
      inside the meninx, using paleo-radiological techniques. We finally link this find
      with experimental data from the neurological literature on the methodology of
      excerebration implemented by ancient Egyptian embalmers.

PMID- 30215157
TI  - Feasibility of a unidirectionally progressive, pancreas-oriented procedure for
      laparoscopic D3 right hemicolectomy.
AB  - BACKGROUND: Complete mesocolic excision (CME) with central ligation or D3
      lymphadenectomy has been reported to provide increased lymph node retrieval with
      the prospect of superior oncological results in colon cancer. However, right
      hemicolectomy with CME or D3 lymphadenectomy by laparoscopy is considered to be a
      technically challenging and time-consuming procedure with a higher risk of
      causing intraoperative injuries. Here, we introduce a novel laparoscopic approach
      for the D3 right hemicolectomy and report its feasibility, safety, and efficacy
      in cancer clearance. METHODS: This purely medial to lateral approach of D3
      hemicolectomy was characterized by the following two features: a series of
      repeated, unidirectional dissections along the superior mesentery vein (SMV) that
      were started below the ileocolic vein and ended at the pancreatic neck, followed
      by the exposure of the whole SMV and its colonic branches precisely before the
      ligation. From January 2012 to December 2015, 58 patients underwent this
      procedure. The short-term outcomes and long-term survival are reported. RESULTS:
      All 58 operations were finished with this procedure successfully, with one injury
      of the jejunal vein. The mean operation time was 164 +/- 28.3 min, the mean blood
      loss was 64 +/- 63.5 ml, and the mean number of retrieved lymph nodes was 28 +/-
      13.9. No mortality or major morbidity was observed. The 4-year overall survival
      was 78%, and the disease-free survival was 77%. CONCLUSION: This novel,
      unidirectionally progressive, pancreas-oriented procedure for laparoscopic
      radical right hemicolectomy with D3 lymphadenectomy is safe and feasible, with
      the merit of providing an easier and safer way to tackle the variable tributaries
      of the SMV.

PMID- 30215158
TI  - Trpm2 Ablation Accelerates Protein Aggregation by Impaired ADPR and Autophagic
      Clearance in the Brain.
AB  - TRPM2 a cation channel is also known to work as an enzyme that hydrolyzes highly
      reactive, neurotoxic ADP-ribose (ADPR). Although ADPR is hydrolyzed by NUT9
      pyrophosphatase in major organs, the enzyme is defective in the brain. The
      present study questions the role of TRPM2 in the catabolism of ADPR in the brain.
      Genetic ablation of Trpm2 results in the disruption of ADPR catabolism that leads
      to the accumulation of ADPR and reduction in AMP. Trpm2-/- mice elicit the
      reduction in autophagosome formation in the hippocampus. Trpm2-/- mice also show
      aggregations of proteins in the hippocampus, aberrant structural changes and
      neuronal connections in synapses, and neuronal degeneration. Trpm2-/- mice
      exhibit learning and memory impairment, enhanced neuronal intrinsic excitability,
      and imbalanced synaptic transmission. These results respond to long-unanswered
      questions regarding the potential role of the enzymatic function of TRPM2 in the
      brain, whose dysfunction evokes protein aggregation. In addition, the present
      finding answers to the conflicting reports such as neuroprotective or
      neurodegenerative phenotypes observed in Trpm2-/- mice.

PMID- 30215159
TI  - Kinesins: Motor Proteins as Novel Target for the Treatment of Chronic Pain.
AB  - Kinesins are one of the neoteric and efficacious targets recently reported to
      play an important role in the initiation and progression of chronic pain.
      Kinesins are anterograde microtubule-based motor proteins that are involved in
      trafficking of receptors including nociceptors and progression of pain. The
      specific kinesin and regulatory proteins interplay is crucial for the delivery of
      nociceptors to the synapse. If this complex and less understood interplay is
      inhibited, it may result in a decrease in central sensitization, and thus
      attenuation of pain. This review is focused on the transportation process of
      receptors/cargos, the role of regulatory proteins influencing the respective
      kinesin, and their relationship with chronic pain. The review also features
      specific strategies adopted by researchers for targeting kinesin and chronic
      pain. Considering the recent preclinical success of kinesin inhibition in pain,
      it is expected that inhibitors for kinesin or enzymes responsible for kinesin
      activation could be developed or repurposed as alternative, safe, and potential
      therapies for the treatment of chronic pain.

PMID- 30215160
TI  - Synchronous Multiple Pituitary Neuroendocrine Tumors of Different Cell Lineages.
AB  - We report clinicopathological features of a large series of synchronous multiple
      pituitary neuroendocrine tumors (PitNETs) of different cell lineages.
      Retrospective review of pathology records from 2001 to 2016 identified 13
      synchronous multiple PitNETs from 1055 PitNETs classified using pituitary cell
      lineage transcription factors, adenohypohyseal hormones, and other biomarkers.
      Clinical, radiological, and histopathological features of these tumors were
      reviewed. The series included seven females and six males. Mean age at diagnosis
      was 55.23 years (range 36-73). Imaging was unavailable for four patients; among
      the other nine, mean tumor size was 2.23 cm (range 0.9-3.9). Five patients had
      acromegaly, four had Cushing disease, and four had clinically non-functional
      tumors. Twelve had double PitNETs; one had a triple PitNET. The most common tumor
      type was corticotroph (n = 8; six densely and one sparsely granulated and one
      Crooke cell; three densely and one sparsely granulated were clinically silent),
      gonadotroph tumors (n = 8), and somatotroph tumors (n = 5; four sparsely
      granulated and one densely granulated somatotroph) were followed by lactotroph
      tumors (n = 4; all sparsely granulated), poorly differentiated Pit-1 lineage
      tumor (n = 1), and unusual plurihormonal tumor (n = 1). A 54-year-old man with
      Cushing disease had MEN1-driven Crooke cell and gonadotroph tumors. The triple
      pitNET consisted of a multilineage plurihormonal tumor associated with a
      gonadotroph and a sparsely granulated lactotroph tumor. The Ki67 (available from
      10 specimens) ranged from 1 to 5% in individual tumors. Radiological and
      biochemical follow-up was available for 10 and 11 patients, respectively.
      Radiological tumor persistence/recurrence was identified in three patients with
      double PitNETs consisting of sparsely granulated lactotroph and gonadotroph
      tumors (n = 1), sparsely granulated somatotroph and silent corticotroph tumors (n
      = 1), and gonadotroph and silent corticotroph tumors (n = 1) with cavernous sinus
      invasion. Biochemical persistence was noted in four patients with double PitNETs
      consisting of sparsely granulated somatotroph and silent corticotroph tumors (n =
      2), gonadotroph and Crooke cell tumors (n = 1), and densely granulated
      somatotroph and silent corticotroph tumors (n = 1). Multiple PitNETs represent
      about 1% of PitNETs and usually have hormone excess due to at least one tumor
      component. Clinical manifestations may be due to the minor component, especially
      in patients with Cushing disease. Invasive growth and aggressive histological
      subtypes predicted disease persistence/recurrence. This series also highlights
      the importance of routine application of pituitary cell lineage transcription
      factors along with hormones to distinguish and subtype multiple synchronous
      PitNETs.

PMID- 30215161
TI  - Mitochondria in Developmental and Adult Neurogenesis.
AB  - Generation of new neurons is a tightly regulated process that involves several
      intrinsic and extrinsic factors. Among them, a metabolic switch from glycolysis
      to oxidative phosphorylation, together with mitochondrial remodeling, has emerged
      as crucial actors of neurogenesis. However, although accumulating data raise the
      importance of mitochondrial morphology and function in neural stem cell
      proliferation and differentiation during development, information regarding the
      contribution of mitochondria to adult neurogenesis processes remains limited. In
      the present review, we discuss recent evidence covering the importance of
      mitochondrial morphology, function, and energy metabolism in the regulation of
      neuronal development and adult neurogenesis, and their impact on memory
      processes.

PMID- 30215163
TI  - The Relationship of the TLR9 and TLR2 Genetic Polymorphisms with Cervical Cancer
      Risk: a Meta-Analysis of Case-Control Studies.
AB  - This meta-analysis aimed to assess the association of common TLR9 and TLR2 gene
      polymorphisms (TLR9 1486 T/C, TLR9 G2848A, and TLR2-196 to -174 del/ins) with
      cervical cancer risk. Studies were searched in Scopus, Pubmed, Embase, and CNKI
      until December 2017. Both fixed-effects and random-effects models were applied to
      combine odds ratio (OR) and 95% confidence intervals (95% CI). A total of 11
      studies including 7856 participants were identified. The pooled estimation
      revealed an increased risk of cervical cancer in Caucasian subjects carrying the
      C allele of the TLR9 1486 T/C polymorphism (OR = 1.46, 95% CI: 1.11-1.92, p =
      0.007), while there was a decreased risk in Mixed subjects carrying the C allele
      (OR = 0.35, 95% CI: 0.15-0.82, p = 0.016). Concerning the TLR9 G2848A
      polymorphism, the A allele was associated with an increased risk of cervical
      cancer in Caucasians (OR = 1.19, 95% CI: 1.02-1.40, p = 0.030), whereas Asian and
      Mixed subjects showed no significant associations. No significant associations
      were demonstrated between the TLR2-196 to -174 del/ins polymorphism and cervical
      cancer. Our findings suggest that the TLR9 1486 T/C and G2848A polymorphisms
      contribute to cervical cancer risk, but there is no association of the TLR2-196
      to -174 del/ins polymorphism with cervical cancer.

PMID- 30215162
TI  - Pancreatic Cancer and Diabetes Mellitus.
AB  - PURPOSE OF REVIEW: The relationship between pancreatic ductal adenocarcinoma
      (PDAC) and diabetes mellitus (DM) is complex. We reviewed the recent medical
      literature regarding the effect of anti-diabetic medication on PDAC risk and
      survival, risk of PDAC in DM, and role of DM in early detection of PDAC. RECENT
      FINDINGS: Studies report that while some anti-diabetic medications (e.g.,
      metformin) may decrease the risk of PDAC, others (insulin, sulfonylureas and
      incretin-based therapies) may increase the risk. However, these observations may
      be subject to protopathic biases. Metformin's anti-tumor activity may have
      influence overall survival of PDAC, but epidemiological reports have largely been
      inconsistent to defend these findings due to heterogeneous methodologies. There
      is congruent data to support the association between DM and PDAC, with an inverse
      relationship to DM duration. Older subjects with new-onset DM are the only known
      high-risk group for PDAC, and strategy using this group for early detection has
      led to development of clinical risk prediction models that define a very high
      risk PDAC group. Role of anti-diabetic medication in PDAC risk modification or
      survival is controversial. With successful efforts to distinguish type 2-DM from
      PDAC-DM using risk-stratifying models, there is an opportunity to initiate
      screening protocols for early detection of PDAC in a sub-set of DM subjects.

PMID- 30215164
TI  - Conceptualizing syntactic categories as semantic categories: Unifying part-of
      speech identification and semantics using co-occurrence vector averaging.
AB  - Co-occurrence models have been of considerable interest to psychologists because
      they are built on very simple functionality. This is particularly clear in the
      case of prediction models, such as the continuous skip-gram model introduced in
      Mikolov, Chen, Corrado, and Dean (2013), because these models depend on
      functionality closely related to the simple Rescorla-Wagner model of discriminant
      learning in nonhuman animals (Rescorla & Wagner, 1972), which has a rich history
      within psychology as a model of many animal learning processes. We replicate and
      extend earlier work showing that it is possible to extract accurate information
      about syntactic category and morphological family membership directly from
      patterns of word co-occurrence, and provide evidence from four experiments
      showing that this information predicts human reaction times and accuracy for
      class membership decisions.

PMID- 30215165
TI  - Platelet-Rich Plasma and the Knee-Applications in Orthopedic Surgery.
AB  - PURPOSE OF REVIEW: To consolidate and synthesize the most recent evidence on the
      effects of platelet-rich plasma (PRP) in the knee with respect to osteoarthritis,
      meniscal injuries, ACL reconstruction, total knee arthroplasty (TKA), and high
      tibial osteotomy. RECENT FINDINGS: PRP has been shown to be more beneficial in
      the context of knee osteoarthritis compared to both placebo and hyaluronic acid.
      Direct comparison with corticosteroid injections has been sparsely studied. It
      has also been shown to improve the clinical postoperative course in meniscal
      injuries and to a lesser extent TKA. Radiographic improvements without clinically
      significant benefits have been observed with ACL reconstructions treated with
      PRP. PRP injections may be more beneficial than other current non-surgical
      management options for specific knee pathologies. Further research should broaden
      the knowledge of PRP effects on the knee, and identify the type of PRP, growth
      factor distribution, and route of administration associated with the most
      benefit.

PMID- 30215167
TI  - Automated Neuron Detection in High-Content Fluorescence Microscopy Images Using
      Machine Learning.
AB  - The study of neuronal morphology in relation to function, and the development of
      effective medicines to positively impact this relationship in patients suffering
      from neurodegenerative diseases, increasingly involves image-based high-content
      screening and analysis. The first critical step toward fully automated high
      content image analyses in such studies is to detect all neuronal cells and
      distinguish them from possible non-neuronal cells or artifacts in the images.
      Here we investigate the performance of well-established machine learning
      techniques for this purpose. These include support vector machines, random
      forests, k-nearest neighbors, and generalized linear model classifiers, operating
      on an extensive set of image features extracted using the compound hierarchy of
      algorithms representing morphology, and the scale-invariant feature transform. We
      present experiments on a dataset of rat hippocampal neurons from our own studies
      to find the most suitable classifier(s) and subset(s) of features in the common
      practical setting where there is very limited annotated data for training. The
      results indicate that a random forests classifier using the right feature subset
      ranks best for the considered task, although its performance is not statistically
      significantly better than some support vector machine based classification
      models.

PMID- 30215166
TI  - Proton Transfer Accounting for Anomalous Collision-Induced Dissociation of Proton
      Bound Hoogsteen Base Pair of Cytosine and Guanine.
AB  - To understand the anomalous collision-induced dissociation (CID) behavior of the
      proton-bound Hoogsteen base pair of cytosine (C) and guanine (G), C:H+???G, we
      investigated CID of a homologue series of proton-bound heterodimers of C, 1
      methylcytosine, and 5-methylcytosine with G as a common base partner. The CID
      experiments were performed in an energy-resolved way (ER-CID) under both multiple
      and near-single collision conditions. The relative stabilities of the protonated
      complexes examined by ER-CID suggested that the proton-bound complexes produced
      by electrospray ionization in this study are proton-bound Hoogsteen base pairs.
      On the other hand, in contrast to the other base pairs, CID of C:H+???G exhibited
      more abundant productions of C:H+, the fragment protonated on the moiety with a
      smaller proton affinity, than that of G:H+. This appeared to contradict general
      prediction based on the kinetic method. However, further theoretical exploration
      of potential energy surfaces found that there can be facile proton transfers in
      the proton-bound Hoogsteen base pairs during the CID process, which makes the
      process accessible to an additional product state of O-protonated C for C:H+
      fragments. The presence of an additional dissociation channel, which in other
      words corresponds to twofold degeneracy in the transition state leading to C:H+
      fragments, effectively doubles the apparent reaction rate for production of C:H+.
      In this way, the process gives rise to the anomaly, the observed pronounced
      formation of C:H+ in the CID of the proton-bound Hoogsteen base pair, C:H+???G.
      Graphical Abstract ?.

PMID- 30215169
TI  - Attention needed for cognitive problems in patients after out-of-hospital cardiac
      arrest: an inventory about daily rehabilitation care.
AB  - AIM: Recent literature and Dutch guidelines for patients with out-of-hospital
      cardiac arrest (OHCA) recommend screening for cognitive impairments and referral
      to cognitive rehabilitation when needed. The aim of this study is to assess the
      uptake of these recommendations for OHCA patients. METHOD: An internet-based
      questionnaire was sent to 74 cardiologists and 143 rehabilitation specialists
      involved in rehabilitation of OHCA patients in the Netherlands. The questionnaire
      covered: background characteristics, availability and content of cognitive
      screening and rehabilitation, organisation of care, experienced need for an
      integrated care pathway including physical and cognitive rehabilitation, barriers
      and facilitators for an integrated care pathway. RESULTS: Forty-five
      questionnaires were returned (16 cardiologists and 29 rehabilitation doctors).
      Thirty-nine percent (n = 17) prescribed cognitive screening. Eighty-nine percent
      underscores an added value of an integrated care pathway. Barriers for an
      integrated care pathway included lack of knowledge, logistic obstacles, and poor
      cooperation between medical specialties. CONCLUSIONS: In the Netherlands, only a
      minority of cardiologists and rehabilitation specialists routinely prescribe some
      form of cognitive screening in OHCA patients, although the majority underscores
      the value of cognitive screening in OHCA patients in an integrated care pathway.
      The uptake of such a care pathway seems hindered by lack of knowledge and
      organisational barriers.

PMID- 30215168
TI  - Development and Evaluation of Compression Coating Gastro-Floating Tablet of
      Alfuzosin Hydrochloride for Zero-Order Controlled Release.
AB  - Alfuzosin hydrochloride is an appropriate candidate drug to prepare a gastro
      retention controlled release dosage form since it demonstrates a narrow
      absorption window in the proximal section of the gastrointestinal tract with a
      short half-life. The purpose of the present study was to develop and optimize a
      gastro-floating tablet of alfuzosin hydrochloride by using the compression
      coating method for controlling drug release in a controlled manner. The floating
      tablets were developed utilizing hydroxypropyl methylcellulose and carbomer as
      matrix materials. The impact of formulation factors on buoyancy property and in
      vitro drug release of the floating tablet was investigated. The "similarity
      factor" (f2) was used as the indicator for the optimization of the formulations.
      Furthermore, in vivo pharmacokinetic study in rabbits and correlation of in
      vitro/in vivo study were also performed. It was found that the optimized
      formulation F9 could float immediately less than 2 min and remain lastingly
      buoyant over 24 h and follow zero-order release kinetics well. In comparison with
      the commercially available prolonged release tablets XATRAL(r) XL, the prepared
      floating tablet exhibited similar pharmacokinetic parameters (Cmax, Tmax, t1/2,
      and AUC0 - t) and plasma concentration versus time profile. Moreover, it
      indicated from the correlation of in vitro/in vivo study that the floating
      tablets exhibited a good correlation of in vitro/in vivo. In summary, the
      compression coating gastro-floating tablets might be a promising drug delivery
      system for alfuzosin hydrochloride to control drug release.

PMID- 30215170
TI  - Molecular autopsy.

PMID- 30215171
TI  - Supranutritional Sodium Selenate Supplementation Delivers Selenium to the Central
      Nervous System: Results from a Randomized Controlled Pilot Trial in Alzheimer's
      Disease.
AB  - Insufficient supply of selenium to antioxidant enzymes in the brain may
      contribute to Alzheimer's disease (AD) pathophysiology; therefore, oral
      supplementation may potentially slow neurodegeneration. We examined selenium and
      selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week
      randomized controlled trial of sodium selenate in AD patients, to assess
      tolerability, and efficacy of selenate in modulating selenium concentration in
      the central nervous system (CNS). A pilot study of 40 AD cases was randomized to
      placebo, nutritional (0.32 mg sodium selenate, 3 times daily), or
      supranutritional (10 mg, 3 times daily) groups. We measured total selenium,
      selenoproteins, and inorganic selenium levels, in serum and CSF, and compared
      against cognitive outcomes. Supranutritional selenium supplementation was well
      tolerated and yielded a significant (p < 0.001) but variable (95% CI = 13.4-24.8
      MUg/L) increase in CSF selenium, distributed across selenoproteins and inorganic
      species. Reclassifying subjects as either responsive or non-responsive based on
      elevation in CSF selenium concentrations revealed that responsive group did not
      deteriorate in Mini-Mental Status Examination (MMSE) as non-responsive group (p =
      0.03). Pooled analysis of all samples revealed that CSF selenium could predict
      change in MMSE performance (Spearman's rho = 0.403; p = 0.023). High-dose sodium
      selenate supplementation is well tolerated and can modulate CNS selenium
      concentration, although individual variation in selenium metabolism must be
      considered to optimize potential benefits in AD. The Vel002 study is listed on
      the Australian and New Zealand Clinical Trials Registry (
      http://www.anzctr.org.au /), ID: ACTRN12611001200976.

PMID- 30215172
TI  - Atypical sleep in critically ill patients on mechanical ventilation is associated
      with increased mortality.
AB  - : Sleep patterns in critically ill patients' polysomnographic sleep studies (PSG)
      are severely abnormal. PURPOSE: We aimed to investigate the association of
      atypical sleep patterns, micro-sleep phenomena (sleep spindles and K-complexes)
      and rapid eye movement (REM) sleep with intensive care unit (ICU), in-hospital
      and 90-day mortality in conscious critically ill patients on mechanical
      ventilation. METHOD: This was a prospective descriptive study. We analysed 52
      PSGs recorded in conscious critically ill patients on mechanical ventilation.
      PSGs were scored according to standard classification when possible. Otherwise,
      modified classification proposed for scoring sleep in critically ill patients was
      used. The association of PSG findings with mortality was studied using logistic
      regression and Weibull model of survival analysis. RESULTS: The presence of
      atypical sleep patterns in accordance with modified sleep scoring classification
      was associated with higher odds for ICU mortality (odds ratio 11.63; p = 0.03).
      The absence of K-complexes was associated with higher odds for ICU mortality
      (odds ratio 11.63; p = 0.03), while the absence of sleep spindles was associated
      with higher odds for in-hospital (odds ratio 7.80; p = 0.02) and 90-day mortality
      (odds ratio 5.51; p = 0.02). Loss of sleep spindles was associated with higher
      mortality risk with cutoff point 90 days (hazard ratio 3.87; p = 0.03).
      CONCLUSIONS: The presence of atypical sleep and absence of normal PSG sleep
      characteristics in conscious critically ill patients on mechanical ventilation
      indicates involvement of sleep producing brain structures in the pathological
      process and is associated with poor outcome.

PMID- 30215173
TI  - Electrochemical sandwich immunoassay for Escherichia coli O157:H7 based on the
      use of magnetic nanoparticles and graphene functionalized with
      electrocatalytically active Au@Pt core/shell nanoparticles.
AB  - A highly sensitive electrochemical sandwich immunoassay is described for
      determination of Escherichia coli O157:H7 (E. coli O157:H7). Silica coated
      magnetite nanoparticles (Fe3O4) were modified with primary antibody to capture E.
      coli O157:H7. Gold-platinum core/shell nanoparticles (Au@Pt NPs) with different
      Pt shell thicknesses were prepared via changing the molar ratio of H2PtCl6 to
      HAuCl4 in the precursor solution. The optimized Au@Pt NPs exhibit enhanced
      activity in the electrocatalytic reduction of hydrogen peroxide (H2O2). The Au@Pt
      NPs were modified with graphene that was functionalized with Neutral Red, and
      then used as an electrochemical label for secondary antibodies and horseradish
      peroxidase (HRP). The sandwich immunocomplexes were magnetically absorbed on a 4
      channel screen printed carbon electrode. Due to the catalysis of the Au@Pt NPs
      and HRP, the signal is strongly amplified in the presence of H2O2 when using
      thionine as the electron mediator. Under optimal conditions, the immunoassay has
      a linear response in the 4.0 * 102 to 4.0 * 108 CFU.mL-1 concentration range,
      with a limit of detection of 91 CFU.mL-1 (at an S/N ratio of 3). Graphical
      abstract Preparation of Au@Pt core/shell nanoparticles with different Pt shell
      thickness (A), rGO-NR (B), rGO-NR-Au@Pt-Ab2-HRP (C) and the preparation and the
      detection process of the immunoassay (D). rGO: reduced graphene oxide, GO:
      graphene oxide, NR: Neutral Red, HRP: horseradish peroxidase, AuNPs: gold
      nanoparticles, Fe3O4@SiO2: Silica coated magnetite nanoparticles, 4-SPCE: 4
      channel screen printed carbon electrode.

PMID- 30215174
TI  - [68Ga]PSMA PET/CT Improves Initial Staging and Management Plan of Patients with
      High-Risk Prostate Cancer.
AB  - PURPOSE: In this retrospective study, we compared the diagnostic value of
      68Gallium prostate-specific membrane antigen positron emission tomography
      computed tomography ([68Ga]PSMA PET/CT) in primary staging of patients with high
      risk prostate cancer (PCa), in comparison to CT, magnetic resonance imaging
      (MRI), and bone scans, and we explored its overall impact on patients' management
      plan. PROCEDURES: Patients with pathological confirmation of PCa with high-risk
      disease were included in this study. Information on patient demographics,
      clinical and histopathological findings with Gleason score and initial prostate
      specific antigen PSA levels, and radiological findings for CT, MRI, bone scan,
      and [68Ga]PSMA PET/CT were retrieved. We stratified the concordance and
      discordance of each imaging modality on per-patient and per-lesion-site bases.
      RESULTS: Twenty-one patients with high-risk disease were included in this study.
      [68Ga]PSMA PET/CT revealed a significantly higher concordance rate (90 %)
      compared to the concordance rates of bone scan (75 %), MRI (73 %), and CT (60 %).
      [68Ga]PSMA PET/CT had a similar accuracy to MRI in detecting prostate lesions but
      a higher accuracy for suspicious pelvic lymph nodes (95.2 % vs. 80 %). It also
      superseded CT scan in detecting suspicious pelvic lymph nodes (95.2 % vs. 75 %)
      and extra-pelvic lymph nodes (100 % vs. 75 %), as well as bone lesions via bone
      scan (100 % vs. 62.5 %). [68Ga]PSMA PET/CT changed the management in 11 patients
      (52 %). CONCLUSIONS: [68Ga]PSMA PET/CT is an invaluable imaging modality in the
      assessment of primary high-risk PCa with great potential for the detection of
      lymph node spread and bone metastases that would impact the management plan.

PMID- 30215175
TI  - Providers' Demeanor Impacts Patient Perceptions of Visit Length.

PMID- 30215176
TI  - An Electronic Best Practice Alert Based on Choosing Wisely Guidelines Reduces
      Thrombophilia Testing in the Outpatient Setting.

PMID- 30215177
TI  - Effects of EHR Use on Patient Participation.

PMID- 30215178
TI  - Trends in Food Insecurity in the USA for Individuals with Prediabetes,
      Undiagnosed Diabetes, and Diagnosed Diabetes.

PMID- 30215179
TI  - Efficacy of Different Types of Exercise-Based Cardiac Rehabilitation on Coronary
      Heart Disease: a Network Meta-analysis.
AB  - BACKGROUND: Exercise-based cardiac rehabilitation (CR) has been recognized as an
      essential component of the treatment for coronary heart disease (CHD).
      Determining the efficacy of modern alternative treatment methods is the key to
      developing exercise-based CR programs. METHODS: Studies published through June 6,
      2016, were identified using MEDLINE, EMBASE, and the Cochrane Library. English
      language articles regarding the efficacy of different modes of CR in patients
      with CHD were included in this analysis. Two investigators independently reviewed
      abstracts and full-text articles and extracted data from the studies. According
      to the categories described by prior Cochrane reviews, exercise-based CR was
      classified into center-based CR, home-based CR, tele-based CR, and combined CR
      for this analysis. Outcomes included all-cause mortality, cardiovascular death,
      recurrent fatal and/or nonfatal myocardial infarction, recurrent cardiac artery
      bypass grafting, recurrent percutaneous coronary intervention (PCI), and hospital
      readmissions. RESULTS: Sixty randomized clinical trials (n = 19,411) were
      included in the analysis. Network meta-analysis (NMA) demonstrated that only
      center-based CR significantly reduced all-cause mortality (center-based: RR =
      0.76 [95% CI 0.64-0.90], p = 0.002) compared to usual care. Other modes of CR
      were not significantly different from usual care with regard to their ability to
      reduce mortality. Treatment ranking indicated that combined CR exhibited the
      highest probability (86.9%) of being the most effective mode, but this finding
      was not statistically significant due to the small sample size (combined: RR =
      0.50 [95% CI 0.20-1.27], p = 0.146). CONCLUSIONS: Current evidence suggests that
      center-based CR is acceptable for patients with CHD. As home- and tele-based CR
      can save time, money, effort, and resources and may be preferred by patients,
      their efficacy should be investigated further in subsequent studies.

PMID- 30215180
TI  - Applying Modern Virtual and Augmented Reality Technologies to Medical Images and
      Models.
AB  - Recent technological innovations have created new opportunities for the increased
      adoption of virtual reality (VR) and augmented reality (AR) applications in
      medicine. While medical applications of VR have historically seen greater
      adoption from patient-as-user applications, the new era of VR/AR technology has
      created the conditions for wider adoption of clinician-as-user applications.
      Historically, adoption to clinical use has been limited in part by the ability of
      the technology to achieve a sufficient quality of experience. This article
      reviews the definitions of virtual and augmented reality and briefly covers the
      history of their development. Currently available options for consumer-level
      virtual and augmented reality systems are presented, along with a discussion of
      technical considerations for their adoption in the clinical environment. Finally,
      a brief review of the literature of medical VR/AR applications is presented prior
      to introducing a comprehensive conceptual framework for the viewing and
      manipulation of medical images in virtual and augmented reality. Using this
      framework, we outline considerations for placing these methods directly into a
      radiology-based workflow and show how it can be applied to a variety of clinical
      scenarios.

PMID- 30215181
TI  - The Use of Probiotic-Loaded Single- and Double-Layered Microcapsules in Cake
      Production.
AB  - To date, the probiotic product development studies have mostly focused on dairy
      based foods. However, endowing bakery products with probiotic properties not only
      provides a variety in food selection but would also potentially improve public
      health when the consumption rates are taken into consideration. This study aimed
      to incorporate single- and double-layered microcapsules containing Saccharomyces
      boulardii, Lactobacillus acidophilus, and Bifidobacterium bifidum, produced by
      spray drying and chilling, in cake production. Microcapsules were added after
      baking to the three different types of cakes (cream-filled, marmalade-filled, and
      chocolate-coated). Additionally, the microcapsules were injected into the center
      of the cake mix and baked at 200  degrees C for 20 min, for plain cake only.
      After baking of plain cakes, the count of S. boulardii and L. acidophilus as
      determined in the double-layered microcapsules produced by spray chilling was 2.9
      log cfu/g. The survivability rates of S. boulardii and L. acidophilus were also
      determined as 67.4 and 70.7% in this microcapsule, respectively. However, there
      were no viable B. bifidum detected after baking. The free forms of these
      probiotics did not survive in any plain cake experiments. Single-layered
      microcapsules produced by spray chilling provided a better protective effect on
      the probiotics in cream-filled and marmalade-filled cake samples during storage,
      particularly the cream-filled cakes. This study showed that combined spray
      chilling and spray drying microencapsulation techniques (double-layered
      microcapsules) could increase the survivability of probiotic microorganisms
      during the cake baking process. During storage, the cake samples had a near
      neutral pH value, and the textural properties deteriorated due to staling.
      However, cake staling had a limited effect on the sensorial attributes of the
      cakes and the samples could be readily consumed after storage for 90 days.

PMID- 30215182
TI  - A Low-Molecular-Weight Compound Derived from Human Leukocytes Determines a
      Bactericidal Activity of the Interferon Preparation.
AB  - The aim of this study was to characterize the structure and mode of action of
      antimicrobials derived from a commercial preparation of alfa-interferon. By
      combination of semi-preparative/analytical reversed-phase high-performance liquid
      chromatography, we isolated and purified a novel active substance based on
      carbohydrate with a complex of amino acids, which determines antimicrobial
      property of commercial preparation of interferon. A size-exclusion chromatography
      was performed and LC/ESI-MS revealed molecular masses of active substance were in
      the range of 180-249 Da. Edman sequencing identified phenylthiohydantoin (PTH)
      derivatives which consisted a set of preliminary (Asp, Glu, Gly, and Ala) and
      minor amino acids (Leu and Thr) at equimolar ratio. Thus, the purified active
      substance is a compound containing the complex of amino acids connected with
      carbohydrate background and called leucidin. Leucidin demonstrated antimicrobial
      activity against the model Escherichia coli (E. coli) K12 strain at a minimal
      inhibitory concentration of 20 MUg mL-1. The revealed antimicrobial mechanism of
      action is associated with violation of the bacterial cell wall leading to a SOS
      response and bacterial autolysis. Despite the preliminary nature of the results,
      obtained data allowed us to discover the previously unknown leukocyte-derived
      antimicrobial molecules.

PMID- 30215183
TI  - Temperature and depth evaluation of the in vitro effects of femtosecond laser on
      oral soft tissue, with or without air-cooling.
AB  - Femtosecond laser is an effective and safe tool in many surgeries, but the
      studies of its effect on oral soft tissue ablation are insufficient. This study
      aimed to investigate the effect of soft tissue ablation with a 1030-nm
      femtosecond laser on temperature and depth. Twenty Sprague-Dawley rat tongue
      specimens were obtained and flat-mounted. The 1030-nm femtosecond laser was
      controlled by a computer system, with a set distance of 4.7 mm between the laser
      aperture and soft tissue surfaces. Ten specimens were ablated for > 1 min with or
      without air-cooling for temperature measurement, while the other 10 specimens
      were ablated for depth measurements, using the following parameters: (i) 3 W,
      2000 mm/s; (ii) 3 W, 4000 mm/s; (iii) 5 W, 2000 mm/s; (iv) 5 W, 4000 mm/s; (v) 8
      W, 2000 mm/s; (vi) 8 W, 4000 mm/s. Temperature changes were measured using a type
      K thermocouple. The depth attained using different power and scanning speed
      settings was measured by a three-dimensional morphology measurement laser
      microscope. Laser power, scanning speed, and air-cooling effects were determined.
      Higher energy and lower speed induced higher temperatures (p < 0.05), which were
      significantly decreased by air-cooling (p < 0.05). The lowest ablation depth was
      obtained at 3 W and 4000 mm/s (72.63 +/- 6.47 MUm) (p < 0.05). The greatest
      incision depth was achieved at 8 W and 2000 mm/s (696.19 +/- 35.37 MUm), or 4000
      mm/s (681.16 +/- 55.65 MUm) (p < 0.05). The 1030-nm femtosecond laser application
      demonstrates clinically acceptable ablation efficiency, without marked
      temperature damage, in a controlled manner.

PMID- 30215184
TI  - Evaluation of theranostic perspective of gold-silica nanoshell for cancer nano
      medicine: a numerical parametric study.
AB  - Using gold-silica nanoshell as a reference nano-agent, this work has performed
      preliminary numerical parametric study to investigate the feasibility and if
      feasible the efficiency of using a single nano-agent to achieve theranostic
      goals. In total, seven generics of gold-silica nanoshells have been tested
      including the R[50,10] (radius of the silica core is 50 nm and thickness of the
      gold shell is 10 nm), R[40,15], R[55,25], R[40,40], R[75,40], R[104,23], and
      R[154,24] nanoshells. A planar tissue model has been constructed as the platform
      for parametric study. For mathematical modeling, radiant transport equation (RTE)
      has been applied to describe the interactions among laser lights, the hosting
      tissue, and the hosted nanoshells and Penne's bio-heat equation has been applied
      to describe the hyperthermia induced by such interactions. Effects of different
      nanoshell generics on the diffuse reflectance signal and hyperthermia temperature
      transition have been simulated, basing on which the potential of a certain
      nanoshell generic as theranostic nano-agent has been evaluated. It has been found
      that it is highly feasible for gold-silica nanoshells to be engineered for
      theranostic purpose and nanoshell generics that are preferentially scattering
      should be explored for good theranostic candidates. On the condition that
      nanoshell generic with the right optical properties has been located, a moderate
      nanoshell retention in the target tissue site is already sufficient to induce
      effective theranostic effects, which indicates that theranostic nano-medicine
      might not have a stringent requirement for the delivery technique. Among
      nanoshells that have been tested, the R[55,25] nanoshell seems to be a promising
      candidate as theranostic nano-agent. Further testing on it is highly recommended.
      Nanoshells that are preferentially absorbing such as the R[50,10] and R[40,15]
      nanoshells are efficient photothermal agent and could be used for therapeutic
      purpose only. However, it is not recommended that preferentially absorbing
      nanoshells being used for theranostic purpose due to possible negative effects
      such nanoshells might bring to the diffuse reflectance signal.

PMID- 30215185
TI  - Er,Cr:YSGG laser associated with acidulated phosphate fluoride gel (1.23% F) for
      prevention and control of dentin erosion progression.
AB  - To evaluate the effect of Er,Cr:YSGG laser, associated with fluoride application,
      on the prevention/control of dentin erosion. Dentin slabs were embedded in
      acrylic resin, flattened, and polished. Half of the specimens were previously
      eroded (10 min immersion in 1% citric acid solution) and half were kept sound.
      The specimens (n = 10 each substrate) were randomly allocated into the
      experimental groups, according to the following treatments: control (no
      treatment); APF gel (1.23% F, 1 min); Er,Cr:YSGG laser irradiation (P1: 0.25 W,
      20 Hz, 2.8 J/cm2, tip S75, beam diameter of 750 MUm, 1 mm away from the surface);
      Er,Cr:YSGG laser irradiation (P2: 0.50 W, 20 Hz, 5.7 J/cm2, tip S75, beam
      diameter of 750 MUm, 1 mm away from the surface); APF gel + Er,Cr:YSGG laser P1
      and; APF gel + Er,Cr:YSGG laser P2. Afterwards, the specimens underwent an
      erosion-remineralization cycling, consisting of a 5-min immersion into 0.3%
      citric acid, followed by 60-min exposure to artificial saliva. This procedure was
      repeated 4*/day, for 5 days. Surface loss (SL, in MUm) was determined by optical
      profilometry. Specimens from each group were analyzed by environmental scanning
      electron microscopy (n = 3). Data were statistically analyzed (alpha = 0.05). For
      the eroded specimens, APF gel presented the lowest SL, being different from the
      control. For the sound specimens, none of the groups differed from the control,
      except for Er,Cr:YSGG laser P2, which presented the highest SL. When substrates
      were compared, only the eroded specimens of the control and APF + Er,Cr:YSGG
      laser P1 Groups showed higher SL. Selective structure removal was observed for
      the laser-treated groups. None of the Er,Cr:YSGG laser parameters were effective
      in the prevention/control dentin erosion. The laser was also unable to enhance
      the protection of fluoride against dentin erosion.

PMID- 30215186
TI  - Spatio-temporal patterns of orchids flowering in Cameroonian rainforests.
AB  - We characterized the flowering patterns of 45 epiphytic orchid species occurring
      in Cameroonian rainforests to explore the environmental and evolutionary forces
      driving their phenology. We used a dataset of 3470 flowering events recorded over
      a period of 11 years in the Yaounde living collection (82% of the flowering
      events) and from in situ observations (18% of the flowering events) to (i)
      describe flowering frequency and timing and synchronization among taxa; (ii) test
      flowering patterns for phylogenetic relatedness at the generic level; and (iii)
      investigate the spatial patterns of phenology. An annual flowering pattern
      prevailed among the species selected for this study. The species-rich African
      genera Angraecum and Polystachya are characterized by subannual and annual
      frequency patterns, respectively. However, in terms of flowering time, no
      phylogenetic signal was detected for the four most diverse genera
      (Ancistrorhynchus, Angraecum, Bulbophyllum, and Polystachya). Results suggest
      also an important role of photoperiod and precipitation as climatic triggers of
      flowering patterns. Moreover, 16% of the taxa cultivated ex situ, mostly
      Polystachya, showed significant differences in flowering time between individuals
      originating from distinct climatic regions, pointing toward the existence of
      phenological ecotypes. Phenological plasticity, suggested by the lack of
      synchronized flowering in spatially disjunct populations of Polystachya, could
      explain the widespread radiation of this genus throughout tropical Africa. Our
      study highlights the need to take the spatial pattern of flowering time into
      account when interpreting phylogeographic patterns in central African
      rainforests.

PMID- 30215189
TI  - Biocompatibility Studies of Gadolinium Complexes with Iminodiacetic Acid
      Derivatives.
AB  - Apart from using as radiopharmaceuticals, iminodiacetic acid derivatives, after
      complexation with gadolinium, have been also tested as MRI CAs (magnetic
      resonance imaging contrast agents) since they show high affinity to hepatocytes
      and therefore provide high-resolution MRI of the liver. The purpose of this study
      was to evaluate the biocompatibility of four gadolinium complexes with
      iminodiacetic acid (IDA) derivatives differing in substituent in aromatic ring by
      estimating their influence on plasma hemostasis, integrity of erythrocyte
      membrane, and toxicity towards human umbilical vein endothelial cells (HUVECs).
      The influence of gadolinium-based CAs on plasma hemostasis was evaluated by
      measuring PT (prothrombin time), APTT (activated partial tromboplastin time), and
      TT (thrombin time). The effects of tested compounds on RBCs (Red Blood Cells)
      were assessed using hemolysis assay and microscopy studies. The influence of
      gadolinium complexes on the barrier properties of HUVECs was assessed by means of
      real-time method based on the measurements of the impedance changes of the cells.
      Gadolinium complexes did not affect significantly PT and TT. APTT measurements
      revealed significant prolongation in the presence of all tested gadolinium
      complexes at the concentration higher than 0.5 MUmol/mL. Hemolysis assay showed
      that compounds with alkyl substituents in benzene ring without halogen atom (1-3)
      do not exert unfavorable effect on the integrity of erythrocyte membrane over the
      entire concentration range. All gadolinium complexes at 1.0 MUmol/mL contribute
      to the decrease in HUVEC viability and integrity. To conclude, the study
      describes biocompatibility studies of gadolinium-based CAs, provides additional
      insight into their potential toxicity associated with systemic administration,
      and underscores the necessity for further research.

PMID- 30215187
TI  - Adrenocortical function during prolonged critical illness and beyond: a
      prospective observational study.
AB  - PURPOSE: For patients suffering from prolonged critical illness, it is unknown
      whether and when the hypothalamus-pituitary-adrenal axis alterations recover, and
      to what extent adrenocortical function parameters relate to sepsis/septic shock,
      to clinical need for glucocorticoid treatment, and to survival. METHODS: Patients
      still in ICU on day 7 (N = 392) and 20 matched healthy subjects were included.
      Morning blood and 24-h urine were collected daily and cosyntropin tests (250 ug)
      performed weekly, repeated 1 week after ICU discharge on the regular ward.
      RESULTS: In all patients free of glucocorticoid treatment up until ICU day 28 (N
      = 347), plasma ACTH always remained low/normal, whereas free cortisol remained
      high (P <= 0.002) explained by reduced binding proteins (P <= 0.02) and
      suppressed cortisol breakdown (P <= 0.001). Beyond ICU day 28 (N = 64 long
      stayers), plasma (free)cortisol was no longer elevated. One week after ICU
      discharge, plasma ACTH and (free)cortisol always rose to supra-normal levels (P
      <= 0.006), most pronounced in long-stayers. Long-stayers always showed low
      incremental total (P <= 0.001), but normal incremental free cortisol responses to
      weekly cosyntropin tests, explained by low cortisol plasma binding proteins.
      Sepsis/septic shock patients were not different from others, patients
      subsequently receiving glucocorticoids (N = 45) were not different from those who
      did not, and non-survivors were distinguishable from survivors only by higher
      (free)cortisol. CONCLUSIONS: Irrespective of sepsis/septic shock, need for
      glucocorticoids and survival, low cortisol plasma binding proteins and suppressed
      cortisol breakdown determine systemic (free)cortisol availability in prolonged
      critical illness, the latter no longer elevated beyond ICU day 28. The uniform
      rise in ACTH and cortisol to supra-normal levels 1 week after ICU discharge
      indicates recovery of a central adrenocortical suppression while in ICU. Low
      cortisol plasma binding invalidates the cosyntropin test.

PMID- 30215188
TI  - Correction to: Epinephrine and short-term survival in cardiogenic shock: an
      individual data meta-analysis of 2583 patients.
AB  - Because of a technical error, the code corresponding to the outcome for the Basir
      et al. cohort was mis-implemented in the original version of our article.
      Characteristics of the cohort are in fact the followings.

PMID- 30215190
TI  - Effect of Fluoride on Small Intestine Morphology and Serum Cytokine Contents in
      Rats.
AB  - This study aimed to determine the effect of excessive fluoride (F) on the
      morphological characteristics of the small intestine and the contents of serum
      cytokines in rats. A total of 48 3-week-old healthy female Sprague-Dawley rats
      were randomly divided into four groups (n = 12). The control group was given
      deionized distilled water, while the F treatment groups were treated with water
      containing 25, 50, and 100 mg F-/L. After 70 days of treatment, the duodenum, the
      jejunum, and the ileum were collected to measure the developmental parameters and
      the distribution of intestinal glycoproteins, goblet cells, and mast cells
      through Pannoramic Viewer, Periodic Acid-Schiff (PAS) staining, Alcian blue and
      periodic acid-Schiff (AB-PAS) staining, and toluidine blue staining,
      respectively. The contents of cytokines, namely, interleukin (IL)-1beta, IL-2, IL
      6, and tumor necrosis factor (TNF)-alpha, in serum were detected via enzyme
      linked immunosorbent assay (ELISA). Results showed that the villus height, crypt
      depth, villus height to crypt depth ratio, goblet cells, glycoproteins, and mast
      cells of the small intestine significantly decreased (P < 0.05 or P < 0.01) in
      the F treatment group. The contents of IL-1beta, IL-2, IL-6, and TNF-alpha were
      significantly lower in the F treatment group than in the control group (P < 0.05
      or P < 0.01). In summary, excessive F intake impaired intestinal development and
      immune function by decreasing the developmental parameters and the distribution
      of immune cells, glycoproteins, and cytokines.

PMID- 30215191
TI  - Association Between Exposure to Heavy Metals and Systemic Sclerosis: the Levels
      of Al, Cd, Hg, and Pb in Blood and Urine of Patients.
AB  - Systemic sclerosis (SSc) is a multisystem connective tissue disease; exogenous
      factors-including heavy metals-may have a role in the disease pathogenesis. In
      this context, a study on the quantification of Al, Cd, Hg, and Pb in blood and
      urine of 27 SSc patients and 30 controls was carried out. Main findings were that
      Al was significantly depleted in blood and increased in urine of SSc patients
      respect to controls; and Pb was found slightly increased in blood and
      significantly decreased in SSc group. In addition, higher Hg levels in urine were
      found in SSc subjects with the higher severity of the disease. Females showed the
      most marked differences in the levels of blood Al, blood Pb, and urine Cd between
      patients and controls. Smoking, hobby, ingestion of contaminated food, job
      exposure may contribute to the bodily levels of Al, Hg, Pb in SSc patients. The
      results indicated that low, chronic, and multiple exposures to heavy metals-also
      through habits, diet, and environment-may influence the risk for SSc.

PMID- 30215192
TI  - Aflatoxin M1 in cow, sheep, and donkey milk produced in Sicily, Southern Italy.
AB  - Samples (n = 485) of raw (n = 394) or heat-treated (n = 91) milk of three
      different species (cow, n = 170; sheep, n = 133; donkey, n = 84), collected 2013
      2016 in Western Sicily (Southern Italy), were analyzed for aflatoxin M1 (AFM1) by
      enzyme-linked immunosorbent assay (ELISA). Positive ELISA results were further
      analyzed by HPLC with fluorescence detection. Both methods had a detection limit
      for AFM1 in milk of 7 ng kg-1. ELISA yielded 12.9 and 5% positives in cows and
      sheep milk, respectively, all samples of donkey milk were negative. Levels of
      AFM1 were in most cases at 0.007-< 0.05 MUg kg-1, only two samples (sheep milk)
      slightly exceeded the European Union maximum level of 0.05 MUg kg-1. Only 6% of
      the samples were positive for AFM1 in a concentration range of 0.008-0.15 MUg kg
      1. Only milk samples collected directly from farms were positive. Overall, the
      levels were much lower than previously reported for Southern Italy cow and sheep
      milk samples purchased in retail stores. The results of this work indicate a
      continuous improvement of the feeding techniques on dairy farms of Southern
      Italy, which is essential to ensure consumers' protection.

PMID- 30215194
TI  - Coherent phenomena in photosynthetic light harvesting: part one-theory and
      spectroscopy.
AB  - The role of non-trivial quantum mechanical effects in biology has been the
      subject of intense scrutiny over the past decade. Much of the focus on potential
      "quantum biology" has been on energy transfer processes in photosynthetic light
      harvesting systems. Ultrafast laser spectroscopy of several light harvesting
      proteins has uncovered coherent oscillations dubbed "quantum beats" that persist
      for hundreds of femtoseconds and are putative signatures for quantum transport
      phenomena. This review describes the language and basic quantum mechanical
      phenomena that underpin quantum transport in open systems such as light
      harvesting and photosynthetic proteins, including the photosystem reaction
      centre. Coherent effects are discussed in detail, separating various meanings of
      the term, from delocalized excitations, or excitons, to entangled states and
      coherent transport. In particular, we focus on the time, energy and length scales
      of energy transport processes, as these are critical in understanding whether or
      not coherent processes are important. The role played by the protein in
      maintaining chromophore systems is analysed. Finally, the spectroscopic
      techniques that are used to probe energy transfer dynamics and that have
      uncovered the quantum beats are described with reference to coherent phenomena in
      light harvesting.

PMID- 30215193
TI  - Multi-spectroscopic studies on the interaction between traditional Chinese herb,
      helicid with pepsin.
AB  - Study on the binding properties of helicid by pepsin systematically using multi
      spectroscopic techniques and molecular docking method, and these interactions
      comprise biological recognition at molecular level and backbone of biological
      significance in medicine concerned with the uses, effects, and modes of action of
      drugs. We investigated the mechanism of interaction between helicid and pepsin by
      using various spectroscopic techniques viz., fluorescence spectra, UV-Vis
      absorption spectra, circular dichroism (CD), 3D spectra, synchronous fluorescence
      spectra and molecular docking methods. The quenching mechanism associated with
      the helicid-pepsin interaction was determined by performing fluorescence
      measurements at different temperatures. From the experimental results show that
      helicid quenched the fluorescence intensity of pepsin via a combination of static
      and dynamic quenching process. The binding constants (Ka) at three temperatures
      (288, 298, and 308 K) were 7.940 * 107, 2.082 * 105 and 3.199 * 105 L mol-1,
      respectively, and the number of binding sites (n) were 1.44, 1.14, and 1.18,
      respectively. The n value is close to unity, which means that there is only one
      independent class of binding site on pepsin for helicid. Thermodynamic parameters
      at 298 K were calculated as follows: DeltaHo (- 83.85 kJ mol-1), DeltaGo (-
      33.279 kJ mol-1), and DeltaSo (- 169.72 J K-1 mol-1). Based on thermodynamic
      analysis, the interaction of helicid with pepsin is driven by enthalpy, and Van
      der Waals' forces and hydrogen bonds are the main forces between helicid and
      pepsin. A molecular docking study further confirmed the binding mode obtained by
      the experimental studies. The conformational changes in the structure of pepsin
      was confirmed by 3D fluorescence spectra and circular dichroism.

PMID- 30215195
TI  - Implementing an Addiction Medicine Module-Based Educational Platform.

PMID- 30215196
TI  - Characteristics of Early Recurrence After Curative Liver Resection for Solitary
      Hepatocellular Carcinoma.
AB  - BACKGROUND: Early recurrence after liver resection of hepatocellular carcinoma
      (HCC) has a great effect on the survival of patients. The aims of this study were
      to identify risk factors for early recurrence and to clarify whether early
      recurrence is related to patient survival rate. METHODS: We identified a total of
      1010 patients with HCC recurrence after hepatic resection between 2009 and 2014
      in Samsung Medical Center and Seoul National University Hospital. Inclusion
      criteria were preoperative solitary tumor Child-Pugh class A and curative
      hepatectomy. Early recurrence was defined as HCC recurrence < 1 year after
      surgery. RESULTS: A total of 628 patients were included in this study: 302 with
      early recurrence and 326 with late recurrence. Multivariate analysis showed that
      HCC grade 3 or 4, tumor size > 3 cm, and microvascular invasion were closely
      associated with early recurrence after liver resection for solitary HCC. When HCC
      recurred, the early recurrence group had large tumor size, increased tumor
      numbers and AFP levels, and high incidence of diffuse intrahepatic recurrence
      compared with the late recurrence group. The overall survival curve for the early
      recurrence group was lower than that for the late recurrence group (P < 0.001).
      Multivariate analysis demonstrated early recurrence was closely associated with
      patient survival. CONCLUSIONS: Patients with early recurrence had different
      characteristics compared to patients with late recurrence after hepatic resection
      in solitary HCC. Early detection of recurrence is necessary through active
      postoperative surveillance in hepatectomy patients with poor prognostic factors.

PMID- 30215197
TI  - Outcomes of Radiation-Associated Esophageal Squamous Cell Carcinoma: The MSKCC
      Experience.
AB  - OBJECTIVE: Esophageal squamous cell carcinoma (ESCC-R) is a rarely encountered
      sequela of chest radiation. Treatment is limited by toxicity with reirradiation
      and complex surgical dissection in a previously radiated field. The clinical
      presentation, prognosis, and treatment selection of ESCC-R remain undefined.
      METHODS: A retrospective review of patients with esophageal squamous cell
      carcinoma at a single institution between 2000 and 2017 was performed to identify
      patients with previous radiation therapy (>= 5 years delay). Clinicopathologic
      characteristics, treatment, and outcomes of ESCC-R (n = 69) patients were
      compared to patients with primary esophageal squamous cell carcinoma (ESCC) (n =
      827). Overall survival (OS) and cumulative incidence of recurrence (CIR) were
      compared using log-rank and Gray's tests, respectively. RESULTS: Median time from
      radiation to ESCC-R was 18.2 years. The majority of ESCC-R patients were female
      and presented with earlier disease and decreased behavioral risk factors. ESCC-R
      treated with surgery alone had worse OS than ESCC (5-year 15 vs 33%; p = 0.045).
      Patients with ESCC-R who received neoadjuvant treatment had higher risk of
      postoperative in-house mortality (16.7 vs 4.2%; p = 0.032). Patients with ESCC-R
      treated with surgery alone and definitive chemoradiation had higher recurrence
      risk than those with neoadjuvant + surgery (5-year recurrence 55 and 45 vs 15%; p
      = 0.101). CONCLUSION: Neoadjuvant chemotherapy or chemoradiation should be used
      whenever possible for ESCC-R as it is associated with lower risk of recurrence.
      The improved survival benefits of aggressive treatment must be weighed against
      the higher associated postoperative risks.

PMID- 30215198
TI  - Dysplasia in Gallbladder: What Should We Do?
AB  - INTRODUCTION: On occasional cholecystectomies, pathologists encounter incidental
      dysplasia in the gallbladder mucosa in the sections submitted per protocol for
      histologic examination. If dysplasia is identified, additional sections are taken
      and/or the gallbladder is entirely submitted to rule out underlying
      adenocarcinoma. The aim of our study was to assess the incidence of subsequent
      identification of invasive adenocarcinoma on additional sections, after an
      incidentally detected dysplasia was noted on a routine cholecystectomy section.
      We also aimed to study the significance of the incidental detection of dysplasia
      and adenocarcinoma, as well as showing the association of gallbladder dysplasia
      to synchronous or metachronous dysplasia/neoplasia in the biliary tract. MATERIAL
      AND METHODS: Our study was approved by the Institutional Review Board. We
      retrospectively identified 41 consecutive cases of routine cholecystectomies from
      1991 to 2017, which had no clinical suspicion of neoplasia, and did not have any
      identifiable mass lesion, but on histopathologic analysis, had neoplasia
      (adenocarcinoma in 4 cases, and dysplasia in 37 cases). The pathologies of all
      cases were reviewed, and the diagnosis and grade of dysplasia were confirmed. The
      clinical information was obtained from the electronic medical records. RESULTS:
      Of the 37 cases with dysplasia, 10 (27%) had high-grade dysplasia (HGD) and the
      remaining showed low-grade dysplasia (LGD). All 4 cases of adenocarcinoma had
      some gross abnormalities (such as porcelain gallbladder, or ruptured, thickened,
      and roughened walls, or a granular mucosa). In contrast, none of the 37 cases
      with dysplasia had any gross abnormality. In 24 (of 37) cases of dysplasia,
      additional sections were submitted (median 8; ranging from 2 to 29), and in 11
      cases, the gallbladder was entirely submitted. None of these cases showed any
      additional pathologic finding on the extra sections. Interestingly, 7 cases with
      dysplasia (18.9%; 6 LGD and 1 HGD) were associated with a concomitant
      pancreatobiliary malignancy. For the remaining 30 cases, follow-up information
      was available in 16 cases (53.3%) with a mean follow-up of 76.5 months (ranging
      from 12 to 204 months). None of these showed any subsequent development of
      pancreatobiliary neoplasms. CONCLUSION: Incidentally detected gallbladder
      dysplasia in a cholecystectomy specimen, without any gross abnormality, has
      almost no risk of a hidden invasive carcinoma. Although cholecystectomy is
      sufficient treatment for gallbladder dysplasia, in our study cohort, 18.9% of
      cases with incidental dysplasia in gallbladder had an associated pancreatobiliary
      carcinoma, which supports the hypothesis of multifocal neoplastic potential in
      the pancreatobiliary tree (also known as field effect). Although follow-up on 16
      cases shows no subsequent development of any other pancreatobiliary neoplasm,
      this number is probably not enough to rule out a serial imaging follow-up of
      patients who have reported dysplasia in their gallbladder, to assess for
      subsequent development of neoplasia elsewhere in the pancreaticobiliary tree.

PMID- 30215199
TI  - Endoscopic Gastrojejunal Revisions Following Gastric Bypass: Lessons Learned in
      More Than 100 Consecutive Patients.
AB  - BACKGROUND: Weight regain and dumping after Roux-en-Y gastric bypass (RYGB) are
      long-term challenges thought to be due to dilation of the gastrojejunal
      anastomosis. The aim of this study was to analyze the feasibility, safety, and
      outcomes of endoscopic gastrojejunal revisions (EGRs) after its introduction in a
      tertiary bariatric surgery center. METHODS: From January 2016 to March 2018, we
      reviewed the electronic records of all patients undergoing EGR with the
      OverStitch suturing device. Demographics, procedure details, and outcomes were
      recorded. RESULTS: There were 107 patients (M:F = 29:78) treated with 133 EGR
      procedures for weight regain (n = 81), dumping syndrome (n = 13), or both (n =
      13) with mean age 47.3 years (R 22.0-72.9) and mean BMI 32.9 kg/m2 (R 22.2-49.8)
      at time of procedure. Mean procedure time was 17.8 min (R 12-41), with median 1
      suture used (R 1-2). No intra-operative or 30-day complications were recorded.
      Mean follow-up time was 9.2 months (R 1-26.8). Patients lost a mean of 4.1, 5.8,
      and 8.0 kg at 3, 6, and 12 months, respectively, after the procedure. Weight loss
      outcomes were significantly better when two compared to one suture was used (p =
      0.036), and for patients with higher starting BMI (p = 0.047). For patients with
      dumping syndrome, 90-100% had treatment response after one or two EGRs.
      CONCLUSION: EGR is feasible and safe for weight regain and dumping syndrome after
      RYGB. It can stabilize weight regain and improve dumping symptoms. Around 20% of
      patients will need repeat EGR within 1 year to achieve sufficient narrowing of
      the anastomosis.

PMID- 30215200
TI  - Surgical Trends in the Management of Duodenal Injury.
AB  - BACKGROUND: Surgical management of traumatic duodenal injury remains challenging.
      While various surgical techniques have been described in the attempt to reduce
      complications and mortality, recent data suggests that surgical approach using
      less invasive procedures might be associated with improved patient outcomes. The
      purpose of this study was to determine the recent trend of surgical procedures
      performed for patients with duodenal injury and their outcome. METHODS: A
      retrospective analysis of the National Trauma Data Bank (NTDB) from 2002 to 2014
      was performed. A total of 2163 patients who sustained a traumatic duodenal injury
      requiring surgical intervention were included. Patient characteristics, injury
      data, procedures, and outcomes were examined. Types of duodenal procedures and
      patient outcomes were compared between two study periods (2002-2006 vs. 2007
      2014). RESULTS: The median age was 27 (IQR 20-39), 78.9% were male, and 63.8%
      sustained penetrating duodenal injury. The median injury severity score was 18
      (IQR 13-26). In patients with isolated duodenal injury, the later study period
      (2007-2014) was significantly associated with the increased use of primary repair
      (OR 1.77; 95% CI 1.11-2.83, p = 0.017). Overall mortality was 11.7%. Patients in
      the later study group were significantly associated with lower odds of inhospital
      mortality (OR 0.47, 95% CI 0.22-0.95, p = 0.041). CONCLUSIONS: A progressive
      trend toward less invasive procedures for duodenal injury was noted in the
      current study. Inhospital mortality has improved in the late study period.

PMID- 30215201
TI  - Financial Impact of Anastomotic Leakage in Colorectal Surgery.
AB  - BACKGROUND: Anastomotic leakage after colorectal surgery is a complication that
      requires additional treatments strongly affecting the economic outcomes. We
      evaluated the use of resources and the economic burden associated with
      anastomotic leaks following colorectal surgery. METHODS: Between January 2015 and
      December 2016, we retrospectively evaluated patients who underwent colorectal
      surgery with primary anastomosis. We compared the medical resource utilization
      and the DRG-based reimbursement of cases with uncomplicated surgery and cases
      complicated by anastomotic leakage. RESULTS: Of the 95 patients included in the
      study, 87 (92%) presented an uneventful postoperative course and 8 patients (8%)
      developed an anastomotic leakage requiring surgery. The statistical analysis
      showed no significant differences in terms of demographics, risks factor, and
      operative results, except the length of hospital stay (9.7 vs. 29.1 days, p <
      0.01). The cost for 87 uncomplicated cases was 1,535,297 EUR (average cost of
      17,647 EUR), whereas the cost of the 8 patients with anastomotic leakage was
      575,822 EUR (average cost of 71,978 EUR) (p < 0.01). For each patient, the
      hospital had 542 EUR profit in the uncomplicated group and a 12,181 EUR loss in
      the anastomotic leakage group (p < 0.01). The multiple R-squared line regression
      analysis showed that factors independently related to costs were age (p = 0.05)
      and length of hospital stay (p = 0.01). CONCLUSIONS: In terms of economic impact,
      the occurrence of an anastomotic leakage has a large negative influence on
      medical resource utilization, so that, despite the complication-related increase
      of DRG-reimbursement, every complicated case represents a financial burden for
      the hospital.

PMID- 30215202
TI  - Circulating Leptin and Branched Chain Amino Acids-Correlation with Intraductal
      Papillary Mucinous Neoplasm Dysplastic Grade.
AB  - BACKGROUND: The most common type of mucinous pancreatic cyst that may progress to
      pancreatic cancer is intraductal papillary mucinous neoplasm (IPMN). Low-risk
      IPMN with low-/moderate-grade dysplasia may be safely watched, whereas high-risk
      IPMN with high-grade dysplasia or invasive components should undergo resection.
      However, there is currently no reliable means of making this distinction. We
      hypothesize that blood concentrations of insulin resistance biomarkers may aid in
      the differentiation of low- and high-risk IPMN. METHODS: Plasma/serum was
      collected from consented patients undergoing pancreatic resection. IPMN diagnosis
      and dysplastic grade were confirmed by surgical pathology. The study included 235
      IPMN (166 low/moderate grade, 39 high grade, 30 invasive). Circulating levels of
      leptin, branched chain amino acids (BCAA), and retinol-binding protein-4 (RBP-4)
      were measured by enzyme-linked immunoassay and correlated with surgical
      pathology. RESULTS: Circulating leptin levels (mean +/- SE) were significantly
      higher in patients with low/moderate IPMN than in high-grade/invasive IPMN
      (15,803 +/- 1686 vs. 10,275 +/- 1228 pg/ml; p = 0.0086). Leptin levels were
      positively correlated with BMI (r = 0.65, p < 0.0001) and were higher in females
      (p < 0.0001). Stratified analysis showed that mean leptin levels were
      significantly different between low/moderate and high/invasive IPMNs only in
      females (24,383 +/- 2748 vs. 16,295 +/- 2040 pg/ml; p = 0.020). Conversely,
      circulating BCAA levels were lower in low/moderate IPMN than in high
      grade/invasive IPMN (0.38 +/- 0.007 vs. 0.42 +/- 0.01 mM; p = 0.011). No
      significant differences in RBP-4 levels were observed. CONCLUSIONS: Circulating
      leptin in females and BCAA correlates with IPMN dysplastic grade and, if combined
      with clinical characteristics, have the potential to improve clinical decision
      making.

PMID- 30215203
TI  - SSAT State-of-the-Art Conference: Advances in the Management of Rectal Cancer.

PMID- 30215205
TI  - Epigenetic markers in basal cell carcinoma: universal themes in oncogenesis and
      tumor stratification? - a short report.
AB  - BACKGROUND: Advanced basal cell carcinomas (BCCs) suffer from a scarcity of
      effective treatment options. Previously, we found that the targetable histone
      methyltransferase EZH2 was upregulated in aggressive BCC subtypes, suggesting
      that epigenetics may play a role in BCC progression. The purpose of this study
      was to determine whether EZH2-associated proteins and marks may be employed for
      the stratification of BCC histologic subtypes. METHODS: Sixty-two specimens (from
      61 patients), representing more or less aggressive BCC histologic subtypes and
      matching non-malignant epidermal cells, were included in this study.
      Immunohistochemistry of H3K27me3, 5hmC, NSD2, MOF and JARID1B was performed to
      assess their putative associations with BCC histologic subtypes, as well as with
      EZH2 and Ki67 expression levels. RESULTS: We found that H3K27me3 and 5hmC
      upregulation was positively correlated with the occurrence of a less aggressive
      BCC histology. The modifications were also positively correlated with each other.
      Interestingly, we found that they were negatively correlated with the expression
      of EZH2, a marker for an aggressive BCC histology. The levels of NSD2, MOF,
      H3K27me3 and 5hmC were found to be universally upregulated in BCCs versus non
      malignant epidermal cells. CONCLUSIONS: Our data reveal an EZH2-associated
      epigenetic marker profile that correlates with histologic signs of BCC
      aggressiveness. Our findings may have diagnostic and therapeutic implications,
      and indicate that epigenetic markers may be shared even with relatively less
      aggressive tumor types, thereby suggesting universal themes.

PMID- 30215206
TI  - Micro-edaphic factors affect intra-specific variations in trace element profiles
      of Noccaea praecox on ultramafic soils.
AB  - The aim of this study was to compare trace element profiles of Noccaea praecox
      (Wulfen) F. K. Mey. growing on ultramafic soils in different habitat types and to
      observe differences in uptake and translocation of trace elements. Physico
      chemical characteristics of the soil and concentrations of P2O5, K2O, Ca, Fe, Mn,
      Zn, Cu, Ni, Cr, Pb, Cd, and Co in plant samples were presented. Biological
      concentration, accumulation, and translocation factors were calculated to
      estimate accumulation potential of different N. praecox accessions. All of the
      studied accessions were Ni hyperaccumulators (with shoot concentrations up to
      14,593 mg kg-1), but with notable differences in accumulation and translocation
      rates. Significant differences in accumulation and translocation patterns of
      trace elements were observed among accessions from habitats characterized as
      serpentine steppes on dry, shallow soils in contrast to the accessions from
      habitats with higher soil moisture, and higher content of organic matter.

PMID- 30215204
TI  - Modulatory Effects of Nicotine on neuroHIV/neuroAIDS.
AB  - Nicotine, one of the key active ingredients in tobacco smoke, exerts its effects
      via binding to nicotinic acetylcholine receptors (nAChRs). Although both negative
      and positive pharmacological effects of nicotine have been shown in numerous
      animals and human studies, its interaction with human immunodeficiency virus-1
      (HIV-1) have not been fully elucidated. Even though combined anti-retroviral
      therapy (cART) limits the progression of HIV-1 to acquired immune deficiency
      syndrome (AIDS), HIV-associated neurocognitive disorders (HAND) remain prevalent.
      There is thus a compelling need to enhance our understanding of HAND-related
      neurologic dysfunction. Some biochemical pathways and physiological dysfunctions
      have been found to be shared by HAND and Alzheimer's (AD) or Parkinson's (PD)
      diseases, and nicotine may exert the same neuroprotection in HAND that has been
      observed in both AD and PD. In the past dozen years, various potential
      therapeutic effects of nicotine such as neuroprotection have been revealed in
      both in vivo and in vitro studies, including using HIV-1 transgenic (HIV-1Tg) rat
      model, which mimics HIV-infected patients receiving cART. In the current review,
      we describe recent progress in the prevalence of HIV/AIDS with and without
      cigarette smoking, some animal models for studying neural dysfunction associated
      with HIV-1 infection, elucidating the modulatory effects of cigarette
      smoking/nicotine on HIV/AIDS, the anti-inflammatory effects of nicotine, and the
      neuroprotective effects observed in HIV-1Tg rat model. Taken together, these
      findings suggest the following: although tobacco smoking does cause deleterious
      effects in both health and disease conditions such as HIV infection, nicotine,
      the significant component of tobacco smoke, has been shown to possess some
      neuroprotective effects in HIV patients, possible via its anti-inflammatory
      activities. It is therefore necessary to study nicotine's dual effects on
      neuroHIV/neuroAIDS in hope of better defining the potential medical uses of
      nicotine or its analogues, and to make them available in a purer and less
      dangerous form.

PMID- 30215207
TI  - Response to "Letter to the editor re: Cheng YH, Chou WC, Yang YF, et al. Environ
      Sci Pollut Res (2018). https://doi.org/10.107/s11356-017-0875-4".

PMID- 30215208
TI  - Levels, distribution, and sources of organophosphate flame retardants and
      plasticizers in urban soils of Shenyang, China.
AB  - Seventy-four soil samples from the road greenbelts, residential areas, drylands,
      waste grasslands, education lands, industrial areas, city parks, and rural
      homesteads of Shenyang city, China, were collected and analyzed for 13
      organophosphate esters (OPEs). OPEs were detected in all analyzed soil samples,
      which indicate that OPEs are ubiquitously environmental contaminants. The ?13OPEs
      concentrations ranged from 0.039 to 0.95 mg/kg dry weight (dw), with the mean and
      median concentrations of 0.23 and 0.16 mg/kg dw, respectively. The pollution
      levels of OPEs in different land use types were different; the concentrations of
      OPEs in dryland soils were maximum and in city park soils were minimum. Of 13
      OPEs, tri-iso-butyl phosphate (TiBP), tris-(1-chloro-2-propyl) phosphate (TCPP),
      tri-butoxyethyl phosphate (TBEP), and tris[2-chloro-1-(chloromethyl) ethyl]
      phosphate (TDCP) were the most abundant OPEs, contributing 42.0 +/- 12.8, 12.4 +/
      2.32, 6.31 +/- 1.88, and 5.76 +/- 1.86% of ?13OPEs, respectively. Principal
      component analysis (PCA) and absolute principal component score-multiple linear
      regression (APCS-MLR) suggested that OPE pollution in soils may be derived from
      atmospheric deposition, road runoff and vehicular traffic emission, and
      wastewater/reclaimed water irrigation and sludge application, their contributions
      were accounting for 62.4, 17.6, and 20.0%, respectively. As compared to the
      results from other studies, the pollution of OPEs in the urban soils of Shenyang
      is relatively serious.

PMID- 30215209
TI  - Use of carbon-based composites to enhance performance of TiO2 for the
      simultaneous removal of nitrates and organics from aqueous environments.
AB  - The simultaneous photocatalytic removal of nitrate from aqueous environment in
      presence of organic hole scavenger using TiO2 has long been explored. However,
      the use of unmodified TiO2 in such reaction resulted in non-performance or
      release of significant amount of undesirable reaction products in the process, a
      problem that triggered surface modification of TiO2 for enhanced photocatalytic
      performance. Previous studies focused on decreasing rate of charge carrier
      recombination and absorption of light in the visible region. Yet, increasing
      active sites and adsorption capacity by combining TiO2 with a high surface area
      adsorbent such as activated carbon (AC) remains unexploited. This study reports
      the potential of such modification in simultaneous removal of nitrates and oxalic
      acid in aqueous environment. The adsorptive behaviour of nitrate and oxalic acid
      on TiO2 and TiO2/AC composites were studied. The Langmuir adsorption coefficient
      for nitrate was four times greater than that of oxalic acid. However, the amount
      of oxalic acid adsorbed was about 10 times greater than the amount of nitrate
      taken up. Despite this advantage, the materials did not appear to produce more
      active photocatalysts for the simultaneous degradation of nitrate and oxalic
      acid. The photocatalytic activity of TiO2 and its carbon-based composites was
      improved by combination with Cu2O particles. Consequently, 2.5 Cu2O/TiO2
      exhibited the maximum photocatalytic performance with 57.6 and 99.8% removal of
      nitrate and oxalic acid, respectively, while selectivity stood at 45.7, 12.4 and
      41.9% for NH4+, NO2- and N2, respectively. For the carbon based, 2.5 Cu2O/TiO2
      20AC showed removal of 12.7% nitrate and 80.3% oxalic acid and achieved 21.6, 0
      and 78.4% selectivity for NH4+, NO2- and N2, respectively. Using the optimal AC
      loading (20 wt%) resulted in significant decrease in the selectivity for NH4+
      with no formation of NO2-, which unveils that selectivity for N2 and low/no
      selectivity for undesirable products can be manipulated by controlling the rate
      of consumption of oxalic acid. In contract, no nitrate reduction was observed
      with Cu2O promoted TiO2-T and its TiO2-(T)-20AC, which may be connected to
      amorphous nature of TiO2-T and perhaps served as charge carrier trapping sites
      that impeded activity.

PMID- 30215212
TI  - ECG-based pulse detection during cardiac arrest using random forest classifier.
AB  - Sudden cardiac arrest is one of the leading causes of death in the industrialized
      world. Pulse detection is essential for the recognition of the arrest and the
      recognition of return of spontaneous circulation during therapy, and it is
      therefore crucial for the survival of the patient. This paper introduces the
      first method based exclusively on the ECG for the automatic detection of pulse
      during cardiopulmonary resuscitation. Random forest classifier is used to
      efficiently combine up to nine features from the time, frequency, slope, and
      regularity analysis of the ECG. Data from 191 cardiac arrest patients was used,
      and 1177 ECG segments were processed, 796 with pulse and 381 without pulse. A
      leave-one-patient out cross validation approach was used to train and test the
      algorithm. The statistical distributions of sensitivity (SE) and specificity (SP)
      for pulse detection were estimated using 500 patient-wise bootstrap partitions.
      The mean (std) SE/SP for nine-feature classifier was 88.4 (1.8) %/89.7 (1.4) %,
      respectively. The designed algorithm only requires 4-s-long ECG segments and
      could be integrated in any commercial automated external defibrillator. The
      method permits to detect the presence of pulse accurately, minimizing
      interruptions in cardiopulmonary resuscitation therapy, and could contribute to
      improve survival from cardiac arrest.

PMID- 30215211
TI  - Environmental hazards associated with open-beach breaking of end-of-life ships: a
      review.
AB  - End-of-life (EOL) ships contribute significantly to the flow of recycled
      industrial Fe and non-Fe metal materials in resource-poor developing countries.
      The ship scrapping (breaking) and recycling industry (SBRI) recycles 90-95% of
      the total weight of EOL ships and is currently concentrated in Bangladesh, India,
      Pakistan, Turkey, and China, due to the high demand for recyclable and reusable
      materials there, an abundance of low-cost labor, and lenient environmental
      regulations. However, the SBRI has long been criticized for non-compliance with
      standards relating to occupational health, labor safety, and to the management of
      hazardous materials. Among the different EOL recycling options, Bangladesh,
      India, and Pakistan use open beaching, a technique that exposes all spheres of
      the environment to the release of hazardous materials from EOL ships. This
      article summarizes the current state of knowledge on the environmental exposure
      of hazardous materials from SBRI, to judge the risks associated with the
      dismantling of EOL ships on open beaches. Our work includes an overview of the
      industry and its recent growth, compares available ship-breaking methods,
      provides an inventory of hazardous releases from EOL ships, and reviews their
      movement into different spheres of the environment. The economic dynamics behind
      open beaching, and apportionment of responsibility for hazards related to it, are
      discussed, in order to generate policy and legal recommendations to mitigate the
      environmental harm stemming from this industry.

PMID- 30215210
TI  - Determination of azole fungal residues in soils and detection of Aspergillus
      fumigatus-resistant strains in market gardens of Eastern France.
AB  - Medical azole antifungals are major compounds used to prevent and to treat
      invasive aspergillosis (IA). Azole fungicides, called DMI (14-alpha demethylase
      inhibitors), are also widely used for crop protection and have been reported to
      be linked to azole-resistant A. fumigatus (aR-Af) development in the environment.
      The aim of this study was to determine whether or not market gardens that spray
      DMIs in Eastern France are also affected by the presence of aR-Af. Forty aR-Afs
      were detected in soils in only two of the four market gardens using DMIs, with
      23% (7/30) and 10% (3/30) of soils containing aR-Af. A total of 87.5% of these
      isolates had the TR34/L98H mutation and 22.5% the TR46/Y121F/T289A mutation on
      the cyp51A gene. Analyses of residual azole concentrations in soils showed the
      presence of difenoconazole for up to 2 years after spraying, but only in soils of
      market gardens where aR-Af was detected. It is very important to identify
      professional activities that could lead to aR-Af development and to develop
      preventive measures for at-risk patients living near professional activities
      using DMIs. We have to better understand why, in some cases, the use of DMI is
      not linked to aR-Af. Measures should be taken to avoid the use of DMI conferring
      cross-resistance to preserve the efficiency of human therapeutics.

PMID- 30215213
TI  - Computer model for leg agility quantification and assessment for Parkinson's
      disease patients.
AB  - Parkinson's disease (PD) is a progressive disorder that affects motor regulation.
      The Unified Parkinson's Disease Rating Scale sponsored by the Movement Disorder
      Society (MDS-UPDRS) quantifies the illness progression based on clinical
      observations. The leg agility is an item in this scale, yet only a visual
      detection of the features is used, leading to subjectivity. Overall, 50 patients
      (85 measurements) with varying motor impairment severity were asked to perform
      the leg agility item while wearing inertial sensor units on each ankle. We
      quantified features based on the MDS-UPDRS and designed a fuzzy inference model
      to capture clinical knowledge for assessment. The model proposed is capable of
      capturing all details regardless of the task speed, reducing the inherent
      uncertainty of the examiner observations obtaining a 92.35% of coincidence with
      at least one expert. In addition, the continuous scale implemented in this work
      prevents the inherent "floor/ceil" effect of discrete scales. This model proves
      the feasibility of quantification and assessment of the leg agility through
      inertial signals. Moreover, it allows a better follow-up of the PD patient state,
      due to the repeatability of our computer model and the continuous output, which
      are not objectively achievable through visual examination. Graphical abstract ?.

PMID- 30215214
TI  - Direct visualizations of air flow in the human upper airway using in-vitro
      models.
AB  - A better understanding of airflow characteristics in the upper airway (UA) is
      crucial in investigating obstructive sleep apnea (OSA), particle sedimentation,
      drug delivery, and many biomedical problems. Direct visualization of air flow
      patterns in in-vitro models with realistic anatomical structures is a big
      challenge. In this study, we constructed unique half-side transparent physical
      models of normal UA based on realistic anatomical structures. A smoke-wire method
      was developed to visualize the air flow in UA models directly. The results
      revealed that the airflow through the pharynx was laminar but not turbulent under
      normal inspiration, which suggested that compared with turbulent models, a
      laminar model should be more suitable in numerical simulations. The flow
      predicted numerically using the laminar model was consistent with the
      observations in the physical models. The comparison of the velocity fields
      predicted numerically using the half-side and complete models confirmed that it
      was reasonable to investigate the flow behaviors in UA using the half-side model.
      Using the laminar model, we simulated the flow and evaluated the effects of UA
      narrowing caused by rostral fluid shift on pharyngeal resistance. The results
      suggested that fluid shift could play an important role in the formation of
      hypopnea or OSA during sleep.

PMID- 30215215
TI  - Fibroblast growth factor-2 enhancement of extinction recall depends on the
      success of within-session extinction training in rats: a re-analysis.
AB  - RATIONALE: One approach to improving exposure therapy for anxiety disorders has
      focused on developing pharmacological adjuncts to enhance extinction, but these
      efforts have produced modest success in clinical trials. Understanding the
      factors that predict the efficacy of adjuncts will help to develop personalized
      treatments for anxiety. OBJECTIVES: We assessed whether individual differences in
      within-session extinction (fear reduction during extinction training) predict the
      extent to which the neurotrophin fibroblast growth factor-2 (FGF2) enhances
      extinction recall in rats. METHODS: We re-analyzed data from five experiments
      that involved administering FGF2 immediately after extinction training;
      extinction recall was assessed the following day. RESULTS: Regression analyses
      revealed that fear responses at the end, but not the start, of extinction
      training predicted extinction recall in FGF2- but not vehicle-treated rats.
      Comparisons between FGF2- and vehicle-treated rats that exhibited better or worse
      extinction recall (determined by a median split in freezing during extinction
      recall) confirmed that FGF2-treated rats exhibiting better extinction recall had
      significantly lower freezing at the end of extinction training relative to FGF2
      treated rats exhibiting poorer extinction recall. In contrast, vehicle-treated
      rats did not differ in within-session extinction based on their performance at
      extinction recall. Finally, even when classified as having poorer extinction
      recall, FGF2-treated rats had stronger extinction recall than vehicle-treated
      rats. CONCLUSIONS: These results suggest that FGF2 may be most effective amongst
      rats that exhibit the lowest fear responses at the end of extinction training.
      Furthermore, FGF2 does not appear to exacerbate fear in rats that exhibit minimal
      fear reduction during extinction training.

PMID- 30215216
TI  - Increased amygdalar metabotropic glutamate receptor 7 mRNA in a genetic mouse
      model of impaired fear extinction.
AB  - RATIONALE: Post-traumatic stress disorder (PTSD) is a devastating anxiety-related
      disorder which develops subsequent to a severe psychologically traumatic event.
      Only ~ 9% of people who experience such a trauma develop PTSD. It is clear that a
      number of factors, including genetics, influence whether an individual will
      develop PTSD subsequent to a trauma. The 129S1/SvImJ (S1) inbred mouse strain
      displays poor fear extinction and may be useful to model this specific aspect of
      PTSD. The metabotropic glutamate receptor 7 (mGlu7 receptor) has previously been
      shown to be involved in cognitive processes and anxiety-like behaviour placing it
      in a key position to regulate fear extinction processes. We sought to compare
      mGlu7 receptor mRNA levels in the S1 strain with those in the robustly
      extinguishing C57BL/6J (B6) inbred strain using in situ hybridisation (ISH) in
      three brain regions associated with fear extinction: the amygdala, hippocampus
      and prefrontal cortex (PFC). RESULTS: Compared to the B6 strain, S1 mice had
      increased mGlu7 receptor mRNA levels in the lateral amygdala (LA) and basolateral
      amygdala (BLA) subdivisions. An increase was also seen in the hippocampal CA1 and
      CA3 subregions of S1 mice. No difference in mGlu7 receptor levels were seen in
      the central nucleus (CeA) of the amygdala, dentate gyrus (DG) of the hippocampus
      or prefrontal cortex. CONCLUSIONS: These data show altered mGlu7 receptor
      expression in key brain regions associated with fear extinction in two different
      inbred mouse strains which differ markedly in their fear extinction behaviour.
      Altered mGlu7 receptor levels may contribute to the deficit fear extinction
      processes seen in fear extinction in the S1 strain.

PMID- 30215217
TI  - Neural circuits for a top-down control of fear and extinction.
AB  - Fear learning and extinction are controlled by the activity of three
      interconnected regions: the amygdala, hippocampus, and prefrontal cortex. Of
      these, the medial prefrontal cortex modulates specific aspects in fear and
      extinction via a top-down regulation. In recent years, extensive progress has
      been made in our understanding of the neural circuits that mediate fear-related
      behaviors and their modulation by ascending systems. The development of new
      experimental techniques is now revealing the details of the intrinsic circuits
      within these structures as well as the connections between them. Here, we
      highlight recent advances in our understanding of how the prefrontal cortex may
      mediate such a top-down regulation.

PMID- 30215219
TI  - Bacterial flagellar switching: a molecular mechanism directed by the logic of an
      electric motor.
AB  - Flagellar rotation regulates the phenomenon of chemotaxis in bacteria. The
      interaction between the stator unit and the rotor unit of the flagellar motors is
      responsible for switching the direction of bacterial flagellar rotation. However,
      the molecular interaction mechanism between the stator (MotA/MotB) and the rotor
      (FliG/FliM/FliN) proteins for the flagellar rotational direction switching was
      not very clear. To address this, the asymmetry in the copies of FliG, FliM, and
      FliN molecules was resolved by reconstructing the switch complex using a modeled
      rotor unit that fulfills the experimentally available geometric constraints. The
      diameter of our assembled switch complex supported the existing literature.
      Experimental evidence and the conformational spread model validates our
      constructed switch complex. Subsequently, normal mode analysis (NMA) on these
      constructed protomer units revealed that the most fluctuating molecule in the
      rotor unit is FliG, which interacts with the bacterial stator through its C
      terminal domain. NMA also facilitates our understanding of the reorientation
      mechanism of FliG between the two states of its flagellar rotation, i.e., counter
      clockwise to clockwise and vice versa. Our observations regarding speed
      regulation, the gap between rotor and stator, and the flagellar switching due to
      the activity of cytoplasmic proteins, indicate that the bacterial flagellar motor
      uses the same mechanism as that of an electric motor. Graphical abstract
      Molecular mechanism of the bacterial flagellar switch.

PMID- 30215220
TI  - Source-based morphometry reveals gray matter differences related to suicidal
      behavior in criminal offenders.
AB  - Relative to the general population, criminal offenders have a higher risk of
      suicide. Neurobiological deficits related to suicidal behavior have been
      identified in the general population, but unexamined in offenders to date. We
      examined the association between brain morphology and suicidal behavior in adult
      male criminal offenders. Brain morphology was examined using voxel-based
      morphometry (VBM) and source-based morphometry (SBM), a multivariate alternative
      to VBM which analyzes brain volume in between-subject spatially independent
      networks. Results showed that offenders with past suicide attempts (n = 19),
      relative to offenders without past suicide attempts (n = 19) and non-offenders (n
      = 26), had reduced gray matter in an SBM component that comprised the posterior
      cingulate, dorsal prefrontal cortex, and amygdala. The SBM source weights were
      significantly associated with suicide attempts independent of other suicide risk
      variables (e.g., depression). VBM results were similar to the SBM results but
      less robust. The results reveal a potential neurobiological marker of
      vulnerability to suicidal behavior among criminal offenders and illustrate the
      utility of multivariate methods of gray matter analyses.

PMID- 30215218
TI  - Lack of deuterium isotope effects in the antidepressant effects of (R)-ketamine
      in a chronic social defeat stress model.
AB  - RATIONALE: (R,S)-ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist,
      exhibits rapid and long-lasting antidepressant effects and anti-suicidal ideation
      in treatment-resistant patients with depression. However, the precise mechanisms
      underlying the antidepressant actions of (R,S)-ketamine are unknown. Although the
      previous report demonstrated the deuterium isotope effects in the antidepressant
      actions of (R,S)-ketamine, the deuterium isotope effects in the antidepressant
      actions of (R)-ketamine, which is more potent than (S)-ketamine, are unknown.
      METHODS: We examined whether deuterium substitution at the C6 position could
      affect antidepressant effects of (R)-ketamine in a chronic social defeat stress
      (CSDS) model. RESULTS: Pharmacokinetic studies showed that levels of (2R,6R)-d1
      hydroxynorketamine [(2R,6R)-d1-HNK], a final metabolite of (R)-d2-ketamine, in
      the plasma and brain after administration of (R)-d2-ketamine (10 mg/kg) were
      lower than those of (2R,6R)-HNK from (R)-ketamine (10 mg/kg), indicating
      deuterium isotope effects in the production of (2R,6R)-HNK. In contrast, levels
      of (R)-ketamine and its metabolite (R)-norketamine in the plasma and brain were
      the same for both compounds. In a CSDS model, both (R)-ketamine (10 mg/kg) and
      (R)-d2-ketamine (10 mg/kg) showed rapid and long-lasting (7 days) antidepressant
      effects, indicating no deuterium isotope effect in the antidepressant effects of
      (R)-ketamine. CONCLUSIONS: The present study suggests that deuterium substitution
      of hydrogen at the C6 position slows the metabolism from (R)-ketamine to (2R,6R)
      HNK in mice. In contrast, we did not find the deuterium isotope effects in terms
      of the rapid and long-lasting antidepressant effects of (R)-ketamine in a CSDS
      model. Therefore, it is unlikely that (2R,6R)-HNK is essential for antidepressant
      effects of (R)-ketamine.

PMID- 30215221
TI  - Automatic segmentation of cervical region in colposcopic images using K-means.
AB  - Colposcopy is an important imaging modality for the detection of cervical
      lesions. The analysis of colposcopic images, especially the effective
      segmentation of the cervical region, has important clinical value in clinical
      application. A cervical segmentation method based on the HSV color mode is
      proposed, which can divide and extract the cervical region in the medical and
      anatomical sense. Firstly, the histogram threshold method is used to analyze the
      histogram (Y) of the colposcopic image. In order to achieve the removal of the
      mirror reflection pretreatment operation in the colposcopy image. Secondly, the
      Preprocessed RGB images is used. Then, the colposcopic image is converted into
      the HSV color space, and the V component is extracted using the K-means
      algorithm. Finally, using the area filter to smooth the edge, the segmented
      cervical region can be obtained. In our study, 110 standard colposcopy images,
      which were tagged by experts, were tested and verified. The segmentation results
      were analyzed and compared using dice coefficients, Jaccard coefficients,
      structural segmentation accuracy specificity, sensitivity, positive predictive
      value, and negative predictive value. Our experimental results show that the
      accuracy, specificity and sensitivity of the method are 87.25%, 81.99% and
      96.70%, respectively. The effectiveness of the method in clinical segmentation
      was verified. Our study has demonstrated that cervical regional segmentation of
      colposcopic images based on HSV color space using K-means has high clinical
      utility and can help medical specialists in the diagnosis of cervical cancer.

PMID- 30215222
TI  - CO2 laser therapy accelerates the healing of ulcers in the oral mucosa by
      inducing the expressions of heat shock protein-70 and tenascin C.
AB  - The treatment of ulceration or stomatitis with laser therapy is known to
      accelerate healing and relieve pain, but the underlying biological mechanism is
      not fully understood. The present study used a mouse model of ulceration to
      investigate the molecular mechanisms by which CO2 laser therapy accelerated the
      wound healing process. An ulcer was experimentally created in the palatal mucosa
      of the mouse and irradiated with light from a CO2 laser. Compared with controls
      (no irradiation), laser irradiation induced the proliferation of epithelial cells
      and faster re-epithelialization of the wound area. Immunohistochemistry
      experiments showed that heat shock protein-70 (HSP70) was expressed mainly in the
      epithelium of normal palatal tissue, whereas there was little tenascin C (TnC)
      expression in the epithelium and mesenchyme under normal conditions. Laser
      irradiation induced HSP70 mRNA and protein expression in the lamina propria as
      well as TnC expression in the mesenchyme underlying the renewing epithelium.
      Epithelial cells and fibroblasts were exposed to heated culture medium or laser
      irradiation to establish whether hyperthermia mimicked the effect of laser
      irradiation. Culture of fibroblasts in heated medium increased the expressions of
      both TnC and TGF-beta1, whereas laser irradiation induced only TnC expression.
      The present study indicates that CO2 laser irradiation exerts a photobiogenic
      effect to up-regulate TnC expression without inducing TGF-beta1 expression. We
      suggest that CO2 laser therapy has an advantage over thermal stimulation.

PMID- 30215223
TI  - Advances in Automated Urinalysis Systems, Flow Cytometry and Digitized
      Microscopy.

PMID- 30215224
TI  - Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility.
AB  - Thyroid disorders are common, affecting more than 10% of people in the US, and
      laboratory tests are integral in the management of these conditions. The
      repertoire of thyroid tests includes blood tests for thyroid-stimulating hormone
      (TSH), free thyroxine, free triiodothyronine, thyroglobulin (Tg), thyroglobulin
      antibodies (Tg-Ab), thyroid peroxidase antibodies (TPO-Ab), TSH receptor
      antibodies (TRAb), and calcitonin. TSH and free thyroid hormone tests are
      frequently used to assess the functional status of the thyroid. TPO-Ab and TRAb
      tests are used to diagnose Hashimoto's thyroiditis and Graves' disease,
      respectively. Tg and calcitonin are important tumor markers used in the
      management of differentiated thyroid carcinoma and medullary thyroid carcinoma
      (MTC), respectively. Procalcitonin may replace calcitonin as a biomarker for MTC.
      Apart from understanding normal thyroid physiology, it is important to be
      familiar with the possible pitfalls and caveats in the use of these tests so that
      they can be interpreted properly and accurately. When results are discordant,
      clinicians and laboratorians should be mindful of possible assay interferences
      and/or the effects of concurrent medications. In addition, thyroid function may
      appear abnormal in the absence of actual thyroid dysfunction during pregnancy and
      in critical illness. Hence, it is important to consider the clinical context when
      interpreting results. This review aims to describe the above-mentioned blood
      tests used in the diagnosis and management of thyroid disorders, as well as the
      pitfalls in their interpretation. With due knowledge and care, clinicians and
      laboratorians will be able to fully appreciate the clinical utility of these
      important laboratory tests.

PMID- 30215225
TI  - Progress in Automated Urinalysis.
AB  - New technological advances have paved the way for significant progress in
      automated urinalysis. Quantitative reading of urinary test strips using
      reflectometry has become possible, while complementary metal oxide semiconductor
      (CMOS) technology has enhanced analytical sensitivity and shown promise in
      microalbuminuria testing. Microscopy-based urine particle analysis has greatly
      progressed over the past decades, enabling high throughput in clinical
      laboratories. Urinary flow cytometry is an alternative for automated microscopy,
      and more thorough analysis of flow cytometric data has enabled rapid
      differentiation of urinary microorganisms. Integration of dilution parameters
      (e.g., creatinine, specific gravity, and conductivity) in urine test strip
      readers and urine particle flow cytometers enables correction for urinary
      dilution, which improves result interpretation. Automated urinalysis can be used
      for urinary tract screening and for diagnosing and monitoring a broad variety of
      nephrological and urological conditions; newer applications show promising
      results for early detection of urothelial cancer. Concomitantly, the introduction
      of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry
      (MALDI-TOF MS) has enabled fast identification of urinary pathogens. Automation
      and workflow simplification have led to mechanical integration of test strip
      readers and particle analysis in urinalysis. As the information obtained by
      urinalysis is complex, the introduction of expert systems may further reduce
      analytical errors and improve the quality of sediment and test strip analysis.
      With the introduction of laboratory-on-a-chip approaches and the use of
      microfluidics, new affordable applications for quantitative urinalysis and
      readout on cell phones may become available. In this review, we present the main
      recent developments in automated urinalysis and future perspectives.

PMID- 30215226
TI  - Effectiveness of Platelet Function Analyzer-100 for Laboratory Detection of Anti
      Platelet Drug-Induced Platelet Dysfunction.
AB  - BACKGROUND: High on-treatment platelet reactivity (HTPR) is the phenomenon
      wherein patients exhibit normal platelet activity in laboratory testing despite
      adequate adherence to anti-platelet treatment. We investigated the detection
      rates of Platelet Function Analyzer (PFA)-100 (Dade Behring AG, Dudingen,
      Switzerland) for drug-induced platelet dysfunction and analyzed potential
      contributors to HTPR with practical PFA-100 data over six years. METHODS: We used
      data from 6,957 patients who underwent PFA-100 testing after receiving aspirin,
      clopidogrel, or non-steroidal anti-inflammatory drugs (NSAIDs). Of these, 6,163
      patients were tested with only the collagen/epinephrine cartridge (Col/EPI) of
      PFA-100; 794 were tested with both Col/EPI and the collagen/ADP cartridge
      (Col/ADP). We calculated PFA-100 closure time (CT) for each drug and compared the
      clinical and laboratory characteristics of the patients with prolonged CTs and
      normal CTs (i.e., HTPR). RESULTS: In Col/EPI, 73.2% (365/499), 72.6% (390/537),
      and 55.3% (3,442/6,228) patients showed prolonged CTs for aspirin, clopidogrel,
      and NSAIDs, respectively. In Col/ADP, prolonged CTs were observed in 37.4%
      (34/91), 43.2% (35/81), and 29.6% (200/676) of patients receiving aspirin,
      clopidogrel, and NSAIDs, respectively. Of the patients tested with both
      cartridges, 88.9% (48/54), 95.3% (41/43), and 89.0% (577/648) of the patients
      receiving aspirin, clopidogrel, and NSAIDs had prolonged CTs, and 10.0% (79/794)
      showed normal CTs regardless of drugs. For clopidogrel users (both cartridges),
      there were more patients with malignancies in the normal CT than prolonged CT
      group. CONCLUSIONS: PFA-100 is not sufficiently effective for laboratory
      screening of drug-induced platelet dysfunction. Malignancy may contribute to
      clopidogrel-related HTPR in PFA-100.

PMID- 30215227
TI  - Evaluation of the SD Bioline Strep A Ultra Test in Relation With Number of Colony
      Forming Units and Color Intensity.
AB  - BACKGROUND: The SD Bioline Strep A Ultra (SD, Yongin, Korea) is a recently
      developed rapid antigen detection test (RADT) for diagnosing bacterial
      pharyngitis caused by Group A Streptococcus, We evaluated the performance of SD
      Bioline Strep A Ultra, using the number of colony forming units and color
      intensity. METHODS: Three throat swabs each were taken from 343 children with
      pharyngitis who visited pediatric clinics. We evaluated the performance of SD
      Bioline Strep A Ultra and compared its positive rate with the number of colony
      forming units, using the Fisher exact test. RESULTS: The sensitivity,
      specificity, positive predictive value, and negative predictive value (95%
      confidence interval) were 97.4% (94.0-99.1%), 90.8% (85.0-94.9%), 93.0% (88.5
      96.1%), and 96.5% (92.0-98.9%), respectively. Positive rate significantly
      differed by number of colony forming units (P=0.021). ROC plot for color
      intensity showed 0.938 of AUC (area under curve). CONCLUSIONS: SD Bioline Strep A
      Ultra showed excellent performance, and its positive rate differed by the number
      of colony counts. This RADT could be used as a sensitive and semi-quantitative
      method detecting bacterial pharyngitis.

PMID- 30215228
TI  - Molecular Epidemiology and Mechanisms of 43 Low-Level Linezolid-Resistant
      Enterococcus faecalis Strains in Chongqing, China.
AB  - BACKGROUND: Enterococcus faecalis strains with low-level resistance to linezolid
      (an oxazolidinone antibiotic) have become common. No large-scale study has
      examined the underlying mechanisms in linezolid-resistant E. faecalis (LRE)
      strains. We investigated these mechanisms and molecular characteristics in
      Chongqing, China. METHODS: A total of 1,120 non-duplicated E. faecalis strains
      collected from August 2014 to June 2017 underwent drug susceptibility testing.
      LRE strains were screened for optrA, cfr, and mutations in the 23S rRNA and
      ribosomal proteins L3 and L4 by PCR amplification and sequencing. Multi-locus
      sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were used for
      epidemiological analysis. RESULTS: All 43 low-level LRE strains (minimum
      inhibitory concentration: 8-16 mg/L) harbored optrA; cfr and 23S rRNA mutations
      were not detected. Novel mutations in the ribosomal proteins L3 and L4-one
      deletion (Q103del) and four substitutions (S113L, T35A, I98V, and N79D)-were
      identified. Novel amino acid substitutions at positions E60K, G197D, and T285P of
      the OptrA protein were observed. MLST revealed 20 types of LRE strains; the most
      common type was ST16 (32.6%). PFGE showed 14 strains of ST16 with unique banding
      patterns. Eight novel sequence types (ST823 to ST830) and one allele (gki95) were
      identified for the first time in China. CONCLUSIONS: optrA plays an important
      role in linezolid resistance and may serve as a marker for resistance screening.
      Since the L3 and L4 mutations did not simultaneously occur in the same strain,
      they play a negligible role in linezolid resistance. Epidemiological
      investigation suggested that the LRE cases were sporadic.

PMID- 30215229
TI  - Shorter Incubation Times for Detecting Multi-drug Resistant Bacteria in Patient
      Samples: Defining Early Imaging Time Points Using Growth Kinetics and Total
      Laboratory Automation.
AB  - BACKGROUND: The transition from manual processing of patient samples to automated
      workflows in medical microbiology is challenging. Although automation enables
      microbiologists to evaluate all samples following the same incubation period, the
      essential incubation times have yet to be determined. We defined essential
      incubation times for detecting methicillin-resistant Staphylococcus aureus
      (MRSA), multi-drug resistant gram-negative bacteria (MDRGN), and vancomycin
      resistant enterococci (VRE). METHODS: We monitored the growth kinetics of MRSA,
      MDRGN, and VRE between two and 48 hours on chromogenic media to establish the
      time points of first growth, single colony appearance, and typical morphology for
      102, 104, 106, and 108 colony forming units/mL. Subsequently, we imaged plates
      inoculated with 778 patient samples after 20, 24, and 36 hours. RESULTS: The
      first growth, single colony appearance, and typical morphology time points were
      inoculum-dependent. First growth appeared after 6-18 hours, 4-18 hours, and 8-48
      hours for MRSA, MDRGN, and VRE, respectively, and single colonies appeared at 12
      18 hours, 6-20 hours, and 12-48 hours, respectively. Typical morphology was
      visible at 14-22 hours and 12-48 hours for MRSA and VRE, but was not determined
      for MDRGN. By examining patient samples, >=98% of MRSA and MDRGN were visible 20
      hours after the start of incubation. Following 24 hours of incubation, only 79.5%
      of VRE were clearly visible on the respective plates. CONCLUSIONS: An incubation
      time of 20 hours is sufficient for detecting MRSA and MDRGN. VRE growth is much
      slower and requires additional imaging after 36 hours.

PMID- 30215230
TI  - Performance Evaluation of the Automated Fluorescent Immunoassay System Rotavirus
      Assay in Clinical Samples.
AB  - BACKGROUND: The Automated Fluorescent Immunoassay System (AFIAS) rotavirus assay
      (Boditech Med Inc., Chuncheon, Korea) is a new rapid antigen test for rotavirus
      detection. We evaluated the performance of this assay for detecting rotaviruses
      and their specific genotypes in clinical stool samples. METHODS: AFIAS rotavirus
      assay was performed in 103 rotavirus-positive and 103 rotavirus-negative stool
      samples (confirmed by both PCR and ELISA), and its results were compared with
      those of PCR, ELISA, and immunochromatographic assay (ICA). We evaluated
      diagnostic sensitivity/specificity, the detectability of rotavirus subtypes,
      lower limit of detection (LLOD), reproducibility, cross-reactivity, and
      interference of AFIAS rotavirus assay. RESULTS: Based on PCR and ELISA results,
      diagnostic sensitivity and specificity of the AFIAS rotavirus assay were both
      99.0%. LLOD results showed that the AFIAS assay had sensitivity similar to or
      greater than ICA and ELISA. High reproducibility was confirmed, and no cross
      reactivity or interference was detected. This assay could detect genotypes
      G1P[8], G2P[4], G3P[8], G4P[6], G4P[8], G8P[4], G8P[8], G9P[4], and G9P[8].
      CONCLUSIONS: The AFIAS rotavirus assay showed high reproducibility, sensitivity,
      and specificity as well as excellent agreement with ELISA, PCR, and ICA. It
      detected the most common as well as unusual genotypes of rotavirus prevalent in
      Korea. It could be a useful on-site assay for rapid, convenient, and cost
      effective detection of rotavirus infection.

PMID- 30215231
TI  - Association of MicroRNA Polymorphisms With Hepatocellular Carcinoma in an Iranian
      Population.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) can modulate various
      biological processes by influencing microRNA (miRNA) biogenesis and altering
      target selection. Common SNPs may alter the processing of miRNA and may be
      associated with hepatocellular carcinoma (HCC). We investigated the relationship
      between miR-499A>G, miR-149C>T, miR-196a2T>C, and miR-146aG>C and HCC
      susceptibility, examining the interaction of the miRNAs with hepatitis B virus
      (HBV). METHODS: We evaluated the associations of miR-499A>G (rs3746444), miR
      149C>T (rs2292832), miR-196a2T>C (rs11614913), and miR-146aG>C (rs2910164) with
      HCC susceptibility in 100 HCC patients (70 males and 30 females) and 120 healthy
      controls (70 males and 50 females), using the PCR-restriction fragment length
      polymorphism method. RESULTS: For miR-499A>G, the frequencies of the AG genotype
      and G allele were higher in female HCC patients than in female controls (P=0.02
      and 0.045, respectively). The frequency of the A allele was higher in HBV
      positive HCC patients than in controls (P=0.019). For miR-149C>T, the frequency
      of the CC genotype was higher in female HCC patients than in female controls
      (P=0.009). For miR-196a2T>C, the frequencies of the CT and CC genotypes and the C
      allele were higher in HBV-positive HCC patients than in controls (P<0.001,
      P=0.009, and P<0.001, respectively). The frequencies of miR-146aG>C polymorphisms
      did not differ between HCC patients and controls. CONCLUSIONS: miR-499A>G, miR
      149C>T, and miR-196a2T>C were associated with the development of HCC in women
      and/or that of HBV-related HCC. They can be considered genetic risk factors for
      the development of HCC among Iranians.

PMID- 30215233
TI  - Role of Salivary Immune Parameters in Patients With Primary Sjogren's Syndrome.
AB  - BACKGROUND: Several factors, including clinical manifestations and laboratory
      data, have been used to evaluate the disease activity of Sjogren's syndrome (SS).
      We investigated saliva indicators of disease activity in primary SS patients.
      METHODS: We enrolled 138 Taiwanese patients with primary SS and 100 Taiwanese
      normal controls. Interleukin (IL)-6, IL-17A, tumor necrosis factor-alpha (TNF
      alpha), and rheumatoid factor (RF)-IgA levels in saliva samples were measured
      using ELISA or fluorescent enzyme-linked immunoassay. Serum IgG, IgA, and IgM
      levels were measured by nephelometry. Erythrocyte sedimentation rate (ESR) was
      measured with an automatic ESR analyzer. The t-test and Pearson correlation test
      were used. RESULTS: IL-6 level was higher in primary SS patients than in normal
      controls (14.23+/-14.77 vs 9.87+/-7.32, P=0.012), but there were no significant
      differences in IL-17A, TNF-alpha, and RF-IgA levels. In primary SS patients, IL-6
      level correlated weakly with ESR and IgG levels (r=0.252, P=0.015, and r=0.248,
      P=0.017, respectively), and TNF-alpha level correlated weakly with IgG level
      (r=0.231, P=0.024). CONCLUSIONS: IL-6 may play a role in SS pathogenesis. Saliva
      IL-6 might be an indicator of disease activity in primary SS patients.

PMID- 30215232
TI  - Performance of Hepatitis B Core-Related Antigen Versus Hepatitis B Surface
      Antigen and Hepatitis B Virus DNA in Predicting HBeAg-positive and HBeAg-negative
      Chronic Hepatitis.
AB  - BACKGROUND: We examined changes in hepatitis B core-related antigen (HBcrAg)
      during the four sequential phases of chronic hepatitis B virus (HBV) infection:
      hepatitis B e antigen (HBeAg)-positive chronic infection (EPCI) and hepatitis
      (EPCH), followed by HBeAg-negative chronic infection (ENCI) and hepatitis (ENCH).
      We compared the performance of serum HBcrAg, hepatitis B surface antigen (HBsAg),
      and HBV DNA in predicting EPCH and ENCH. METHODS: We enrolled 492 consecutive
      patients: 49 with EPCI, 243 with EPCH, 101 with ENCI, and 99 with ENCH. HBcrAg
      was detected by chemiluminescent enzyme immunoassays. HBsAg and HBeAg were
      detected by chemiluminescent microparticle immunoassays. HBV DNA was detected by
      real-time PCR. Predictive performance of HBcrAg, HBsAg, and HBV DNA was evaluated
      using ROC curves. RESULTS: Areas under ROC curves (AUCs) of HBcrAg, HBsAg, and
      HBV DNA for predicting EPCH were 0.738, 0.812, and 0.717, respectively; optimal
      cutoffs were <=1.43*105 kU/mL, <=1.89*104 IU/mL, and <=3.97*107 IU/mL, with
      sensitivities and specificities of 66.3% and 77.6%, 65.0% and 93.9%, and 60.5%
      and 79.6%, respectively. AUCs of HBcrAg, HBsAg, and HBV DNA for predicting ENCH
      were 0.887, 0.581, and 0.978, respectively; optimal cutoffs were >26.8 kU/mL,
      >2.29*102 IU/mL, and >8.75*103 IU/mL, with sensitivities and specificities of
      72.7% and 95.1%, 86.9% and 39.6%, and 89.9% and 92.1%, respectively. CONCLUSIONS:
      HBsAg and HBV DNA were the best predictors of EPCH and ENCH, respectively. HBcrAg
      is an important surrogate marker for predicting EPCH and ENCH.

PMID- 30215234
TI  - Prevalence of Hepatitis B Virus (HBV) Among Blood Donors in Eastern Saudi Arabia:
      Results From a Five-Year Retrospective Study of HBV Seromarkers.
AB  - BACKGROUND: Transfusion-transmissible hepatitis B virus (HBV) infection is a
      major problem worldwide. Recently, confirmatory nucleic acid tests (NATs) for HBV
      DNA have been employed in several countries. We assessed the prevalence and
      yearly trends of HBV infection in blood donors in the Eastern Province of Saudi
      Arabia, screening for HBV surface antigen (HBsAg), antibody against HBV core
      antigen (anti-HBc), and HBV DNA. METHODS: Between 2011 and 2015, a total of
      22,842 donors were screenedfor HBsAg, anti-HBc, and HBV DNA using the HBsAg
      Qualitative II kit (Abbott, Ireland Diagnostics Division, Sligo, Ireland),
      ARCHITECT Anti-hepatitis B core antigen antibody (HBc) II Assay kit (Abbott GmbH
      & Co. KG, Wiesbaden, Germany), and NAT Procleix Ultrio Elite Assay kit (Grifols
      Diagnostic Solutions Inc., Los Angeles, CA, USA), respectively. RESULTS: A total
      of 739 (3.24%) donors were HbsAg(+), anti-HBc(+), or HBV DNA(+); 63 (0.28%) were
      HbsAg(+), anti-HBc(+), and HBV DNA(+). Twelve (0.05%) were anti-HBc(+) and HBV
      DNA(+) but HBsAg(-); they were considered to have occult infection. Further, 664
      (2.91%) were HBsAg(-) but anti-HBc(+), indicating chronic or resolving infection.
      HBV prevalence increased significantly from 2011 to 2012, increased marginally
      till 2013, and showed a decreasing trend from 2013 (P>0.05). CONCLUSIONS: The
      five-year prevalence of HBV infection among blood donors in the Eastern Province
      of Saudi Arabia (3.24%) is lower than that reported for other regions in the
      country. The occult HBV infection rate of 0.05% emphasizes the importance of NATs
      in isolating potential infectious blood units.

PMID- 30215235
TI  - Performance Evaluation of the Beckman Coulter DxN VERIS Hepatitis B Virus (HBV)
      Assay in Comparison With the Abbott RealTime HBV Assay.
AB  - The detection and quantification of hepatitis B virus (HBV) DNA plays an
      important role in diagnosing and monitoring HBV infection as well as in assessing
      the therapeutic response. We compared the analytical performance of a random
      access, fully automated HBV assay-DxN VERIS Molecular Diagnostics System (Beckman
      Coulter, Brea, CA, USA)-with that of Abbott RealTime HBV assay (Abbott
      Laboratories, Des Plaines, IL, USA). The between-day precision of the VERIS assay
      ranged from 0.92% (mean 4.68 log IU/mL) to 4.15% (mean 2.09 log IU/mL) for pooled
      sera from HBV patients. HBV DNA levels measured by the VERIS HBV assay correlated
      with the calculated HBV DNA levels (r2=0.9994; P<0.0001). The lower limit of
      quantification was estimated as 8.76 IU/mL (Probit analysis, 95% confidence
      interval: 7.32-12.00 IU/mL). Passing-Bablok regression analysis showed good
      concordance between the VERIS and RealTime assays for 187 chronic HBV samples (y=
      0.2397+0.9712x; r=0.981), as well as for 20 drug-resistant HBV genotype C
      positive samples (y=-0.5415+0.9954x; r=0.961). The VERIS assay demonstrated
      performance similar to the RealTime assay and is suitable for high-throughput HBV
      DNA monitoring in large hospital laboratories.

PMID- 30215237
TI  - First Case of Plasma Cell Myeloma With Brown Tumor Features Unrelated to
      Hyperparathyroidism.

PMID- 30215236
TI  - Dose Estimation Curves Following In Vitro X-ray Irradiation Using Blood From Four
      Healthy Korean Individuals.
AB  - Cytogenetic dosimetry is useful for evaluating the absorbed dose of ionizing
      radiation based on analysis of radiation-induced chromosomal aberrations. We
      created two types of in vitro dose-response calibration curves for dicentric
      chromosomes (DC) and translocations (TR) induced by X-ray irradiation, using an
      electron linear accelerator, which is the most frequently used medical device in
      radiotherapy. We irradiated samples from four healthy Korean individuals and
      compared the resultant curves between individuals. Aberration yields were studied
      in a total of 31,800 and 31,725 metaphases for DC and TR, respectively, obtained
      from 11 X-ray irradiation dose-points (0, 0.05, 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4,
      and 5 Gy). The dose-response relationship followed a linear-quadratic equation,
      Y=C+alphaD+betaD2, with the coefficients C=0.0011 for DC and 0.0015 for TR,
      alpha=0.0119 for DC and 0.0048 for TR, and beta=0.0617 for DC and 0.0237 for TR.
      Correlation coefficients between irradiation doses and chromosomal aberrations
      were 0.971 for DC and 0.6 for TR, indicating a very strong and a moderate
      correlation, respectively. This is the first study implementing cytogenetic
      dosimetry following exposure to ionizing X-radiation.

PMID- 30215238
TI  - First Case of Catheter-related Malassezia pachydermatis Fungemia in an Adult.

PMID- 30215239
TI  - Planned Transfusion of D-Positive Blood Components in an Asia Type DEL Patient:
      Proposed Modification of the Korean National Guidelines for Blood Transfusion.

PMID- 30215240
TI  - Compound Heterozygous Pathogenic Variants of the 15-Hydroxyprostaglandin
      Dehydrogenase Gene in a Patient With Hypertrophic Osteoarthropathy: First Case in
      Korea.

PMID- 30215241
TI  - A Novel Pathogenic RS1 Variant (c.362delA) in a Korean Patient With Late-onset X
      linked Retinoschisis.

PMID- 30215242
TI  - Erratum: Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration
      Distributions and Resistance-related Gene Mutations in Multidrug-resistant and
      Extensively Drug-resistant Tuberculosis in Korea.
AB  - This corrects the article on p. 563 in vol. 38, PMID: 30027700.

PMID- 30215243
TI  - Simulation in Ophthalmic Training.
AB  - Vision impairment and blindness arise both as a cause, and a consequence, of
      poverty. Achievement of the United Nations Sustainable Development Goals in
      providing universal access and equity in eye care, both within and between among
      countries, remains challenging. A severe shortage of eye care providers is
      creating unnecessary blindness and vision impairment in developing communities
      worldwide. Education and training develops and strengthens the capacity of
      emerging nations to contribute to global eye health and the World Health
      Organization Development Goals in an effective and sustainable way. Although
      relative to other medical professions, adoption of simulation in ophthalmic
      training has been relatively slow, simulation potentially offers reduced training
      costs, increased accessibility, objective measurement of training outcomes, and
      improvements in patient safety during and after clinician training, all of which
      can help address the global burden of vision impairment and blindness. Simulation
      training offers advantages over apprenticeship models, the traditional mode of
      transferring knowledge and skills in medicine and health, which suffers from
      imperfect transference due to inherent biases, heuristic and idiosyncratic
      expectations of experts, and subjective measures of outcomes. Simulation does not
      completely do away with these confounders because it is made to fit into
      established curricula, making it difficult to measure effectiveness of the
      simulation in isolation. The power of simulation training for resource-limited
      regions and countries is immense in offering cost-effective training in-country;
      however, it is important that any such tools are developed within the context of
      the limitations in situ.

PMID- 30215244
TI  - Combination of analytical and experimental optical clearing of rodent specimen
      for detecting beta-carotene: phantom study.
AB  - Recently, compression optical clearing (OC) was applied to detect dermal
      carotenoid using reflection spectroscopy. To enhance the precision and accuracy
      of reflection spectroscopy to better detect the spectral absorption of beta
      carotene inside biological phantom, here, we simultaneously use compression and
      immersion OC using dimethyl sulfoxide. In addition, we analytically extract the
      absorption coefficient of beta-carotene using diffuse reflectance spectroscopy
      (as an analytical OC). Our results show that the presented analytical OC can be
      applied alone as a noninvasive method to measure cutaneous chromophores at deep
      tissues. Finally, we also improve the ability of the analytical clearing method
      mediated with experimental OC. Our result demonstrates that the combination of
      analytical and experimental clearing methods enhance the ability of diffuse
      reflection spectroscopy for extracting the absorption coefficient of beta
      carotene as one of the chromospheres inside biological phantom.

PMID- 30215245
TI  - Photoacoustic speckle tracking for motion estimation and flow analysis.
AB  - This study explores photoacoustic (PA) speckle tracking to characterize flow as
      an alternative to ultrasound (US) speckle tracking or current PA flow imaging
      methods. In cases where tracking of submicrometer particles is required, the US
      signal-to-noise ratio and contrast might be low due to limited reflectivity of
      subwavelength size targets at low concentrations. However, it may be possible to
      perform more accurate velocimetry using PAs due to different contrast mechanisms
      utilized in PA imaging. Here, we introduce a PA-based speckle tracking method
      that overcomes the directional dependence of Doppler imaging and the limited
      field of view of current correlation-based methods used in PA flow imaging. The
      feasibility of this method is demonstrated in a potential application-minimally
      invasive diagnosis of ventricular shunt malfunction, where the velocity of
      optically absorbing particles was estimated in a shunt catheter using block
      matching of PA and US signals. Overall, our study demonstrates the potential of
      the PA-based motion tracking method under various flow rates where US imaging
      cannot be effectively used for specking tracking because of its low contrast and
      low signal-to-noise ratio.

PMID- 30215247
TI  - Mesoporous Colloidal Photonic Crystal Particles for Intelligent Drug Delivery.
AB  - Particle-based delivery systems demonstrate a pregnant value in the fields of
      drug research and development. Efforts to advance this technology focus on the
      fabrication of functional particles with enhanced efficiency and performance for
      drug delivery. Here, we present a new type of mesoporous colloidal photonic
      crystal particle (MCPCP)-based drug-delivery system with distinct features. As
      the MCPCPs were constructed by self-assembling monodisperse mesoporous
      nanoparticles in microfluidic droplet templates, they were composed of
      hierarchical macro- and mesoporous structures and could provide plenty of
      nanopores and interconnected nanochannels for synergistic loading of both micro-
      and macromolecule drugs with large quantity and sustained release. In addition,
      by integrating the stimuli-responsive poly( N-isopropylacrylamide) hydrogel into
      the MCPCPs and employing it as a "gating" to control the opening of the macro-
      and mesopores, the MCPCP delivery systems were imparted with the function of
      controllable release. More attractively, as the average refractive index of the
      MCPCPs was decreased during the release of the loaded actives, the photonic band
      gaps of the MCPCPs blue-shifted correspondingly; this provided a novel stratagem
      for real-time self-reporting of the therapeutic agent release process of the
      MCPCPs. Hence, the MCPCPs are ideal for intelligent drug delivery because of
      these dramatical features.

PMID- 30215246
TI  - Global Sources of Fine Particulate Matter: Interpretation of PM2.5 Chemical
      Composition Observed by SPARTAN using a Global Chemical Transport Model.
AB  - Exposure to ambient fine particulate matter (PM2.5) is a leading risk factor for
      the global burden of disease. However, uncertainty remains about PM2.5 sources.
      We use a global chemical transport model (GEOS-Chem) simulation for 2014,
      constrained by satellite-based estimates of PM2.5 to interpret globally dispersed
      PM2.5 mass and composition measurements from the ground-based surface particulate
      matter network (SPARTAN). Measured site mean PM2.5 composition varies
      substantially for secondary inorganic aerosols (2.4-19.7 MUg/m3), mineral dust
      (1.9-14.7 MUg/m3), residual/organic matter (2.1-40.2 MUg/m3), and black carbon
      (1.0-7.3 MUg/m3). Interpretation of these measurements with the GEOS-Chem model
      yields insight into sources affecting each site. Globally, combustion sectors
      such as residential energy use (7.9 MUg/m3), industry (6.5 MUg/m3), and power
      generation (5.6 MUg/m3) are leading sources of outdoor global population-weighted
      PM2.5 concentrations. Global population-weighted organic mass is driven by the
      residential energy sector (64%) whereas population-weighted secondary inorganic
      concentrations arise primarily from industry (33%) and power generation (32%).
      Simulation-measurement biases for ammonium nitrate and dust identify uncertainty
      in agricultural and crustal sources. Interpretation of initial PM2.5 mass and
      composition measurements from SPARTAN with the GEOS-Chem model constrained by
      satellite-based PM2.5 provides insight into sources and processes that influence
      the global spatial variation in PM2.5 composition.

PMID- 30215248
TI  - DFT Provides Insight into the Additive-Free Conversion of Aqueous Methanol to
      Dihydrogen Catalyzed by [Ru(trop2dad)]: Importance of the (Electronic)
      Flexibility of the Diazadiene Moiety.
AB  - The mechanism for complete dehydrogenation of aqueous methanol to CO2 and three
      equivalents of H2 catalyzed by [Ru(trop2dad)] was investigated with DFT (trop2dad
      = 1,4-bis(5 H-dibenzo[ a, d]cyclohepten-5-yl)-1,4-diazabuta-1,3-diene). To date,
      this is the only catalyst that promotes the acceptorless dehydrogenation of
      aqueous methanol in homogeneous phase under mild conditions without the addition
      of an additive (base, acid, or a secondary catalyst). A detailed understanding of
      the mechanism of this transformation may therefore be of significant importance
      for the conversion of liquid organic fuels. Previous computational studies using
      simplified models of the catalyst suggested entirely ligand-centered reaction
      pathways with rather high-energy barriers for complete dehydrogenation of aqueous
      methanol. These are, however, not consistent with the experimental data. In the
      present paper, we reveal a different reaction mechanism for aqueous methanol
      dehydrogenation that involves metal-ligand cooperativity involving the diazadiene
      (dad) ligand and has substantially lower barriers, in good agreement with the
      experimental data. The dad moiety of the ligand actively participates in the
      alcohol activation mechanism. In the first step of the reaction, the dad ligand
      rearranges from a sigma- to a pi-bound coordination mode. This adjusts the
      electronic structure of both the metal and the ligand, leading to an enhanced
      Bronsted basicity of the nitrogen centers and higher Lewis acidity of the
      ruthenium center. As a result, concerted proton-hydride transfer to/from metal
      hydride and N-protonated dad-ligand moieties becomes possible, leading to low
      barrier metal-ligand cooperative elementary steps for alcohol activation and H2
      elimination.

PMID- 30215249
TI  - HP-beta-CD Functionalized Fe3O4/CNPs-Based Theranostic Nanoplatform for pH/NIR
      Responsive Drug Release and MR/NIRFL Imaging-Guided Synergetic Chemo/Photothermal
      Therapy of Tumor.
AB  - The combination of chemotherapy and photothermal therapy has aroused great
      interest due to its better antitumor effect than either single therapy alone.
      Herein, we report on the development of hydroxypropyl-beta-cyclodextrin
      functionalized Fe3O4/carbon nanoparticles (HFCNPs) for pH/near-infrared (NIR)
      responsive drug release, magnetic resonance/NIR fluorescence (MR/NIRFL) imaging
      guided combined chemo/photothermal therapy. The high doxorubicin (DOX) loading
      capacity (61.2%) and controlled drug release by NIR irradiation and weak acid
      microenvironment render HFCNPs a good vector for DOX delivery and controlled
      release. Moreover, the MR/NIRFL dual-modal imaging was used to define the tumor
      location, size, and boundary and to track the tumor accumulation of HFCNPs and
      their biodistribution. The efficient accumulation and prolonged retention time of
      the nanoparticles in tumor are beneficial to tumor therapy. Taking advantage of
      the NIR laser-induced heating and hence promoted drug permeation, remarkable
      tumor inhibition was realized by synergetic chemo/photothermal therapy. In
      conclusion, the current work offers a promising approach to the development of
      smart and efficient multimodal cancer-targeted nanotheranostics.

PMID- 30215250
TI  - Thermally Controlled Phase Transition of Low-Melting Electrode for Wetting-Based
      Spontaneous Top Contact in Molecular Tunnel Junction.
AB  - Top contacts for molecular-scale electronic devices should exhibit reliable and
      reproducible electronic performance. This goal is challenging and difficult to
      achieve because metals are usually evaporated under high-energy conditions that
      easily damage delicate organic surfaces, and complicated nanofabrication
      processes are needed for achieving geometrically defined small contact areas.
      Soft top contacts that are made by users under ambient conditions can circumvent
      this problem but often show user-dependence. This paper describes that thermally
      controlled phase transition (TCPT) of low-melting (29.76  degrees C) electrode
      comprising gallium covered with a self-passivating oxide layer could be useful to
      form reliable, spontaneous (i.e., user-independent) top contacts over delicate
      ultrathin organic films such as self-assembled monolayers (SAMs). As a proof-of
      concept, we demonstrate that the phase transition from solid to non-Newtonian
      liquid for gallium electrode is tuned under mild thermal conditions (room
      temperature to ~50  degrees C), which does not damage the organic component and
      ensures conformal, geometrically defined contacts. The contact force
      predominantly depends on wetting of compliant liquid gallium onto SAMs, upon
      heating, not on user-pressure. Indeed, the TCPT-based large-area tunnel junctions
      on SAMs of n-mercaptoalkanoic acids yield markedly narrow dispersion of tunneling
      current density (sigmalog| J| = 0.04-0.19) and tunneling attenuation coefficient
      (beta = 0.92 +/- 0.02 nC-1) consistent with the literature value. We envisage
      that our approach can be harnessed to accomplish liquid metal-based tunnel
      junctions without significant user-to-user variations and hence useful for
      reliable understanding of charge transport across molecules and practical
      applications.

PMID- 30215251
TI  - Response to Interpretation of Mass Spectral Data for the Cisplatin 1,2
      Intrastrand Guanine-Guanine Adduct.

PMID- 30215252
TI  - Passive Micropump for Highly Stable, Long-Termed, and Large Volume of Droplet
      Generation/Transport Inside 3D Microchannels Capable of Surfactant-Free and
      Droplet-Based Thermocycled Reverse Transcription-Polymerase Chain Reactions Based
      on a Single Thermostatic Heater.
AB  - It is still one key challenge for traditional passive micropumps (e.g., surface
      tension micropump, hydrostatic micropump, enzymatic micropump, degassed
      polydimethylsiloxane (PDMS) micropump, etc.) to transport a large volume of two
      phased fluid for a long period. Herein we propose a user-friendly and passive
      approach to realize the microdroplet generation by waiving expensive or complex
      equipment. The automation principle is systemically studied in this paper. It is
      affirmed that this micropump can continuously transport over 2000 MUL of two
      phased aqueous/oil microdroplets over a 4 m long 3D microchannel for 8 h. In
      addition, variations in flow rate are little within each hour-period, and the
      evaporation bubbles can be well suppressed under high temperature (95  degrees
      C). As a proof of this concept, the novel micropump is applied to droplet-based
      continuous flow real-time polymerase chain reactions (PCRs), which only require
      several disposable syringes for oil/aqueous-phase storage, two 34 gauge needles
      for droplet generation, a Teflon tube for PCR amplification, and a single
      thermostatic heater for the thermal cycle. The results suggest this droplet
      generation method is acceptable for a house-made setup of microfluidic PCRs.
      Besides, the amplification efficiency of the droplet-based microcontinuous flow
      PCRs here is much higher than the plug-based microcontinuous flow PCRs in our
      previous work and reaches 91% of the commercial qPCR thermocycler for the target
      gene of Rubella virus (Rubv). Without expensive microfabrication instruments,
      this novel method is more accessible to nonprofessionals than previous reports
      and would extend the droplet-based applications to in-field and real-time
      analysis.

PMID- 30215253
TI  - CuS@MOF-Based Well-Designed Quercetin Delivery System for Chemo-Photothermal
      Therapy.
AB  - Quercetin (QT) is one promising candidate for the treatment of various cancers
      with virtually no toxic side effects. However, its anticancer effect is severely
      restricted by its poor bioavailability, low water solubility, and chemical
      instability in the neutral and alkaline medium. Herein, zeolitic imidazolate
      framework-8 (ZIF-8) is first reported as the multifunctional nanoplatform to the
      codelivery of quercetin as an anticancer agent and CuS nanoparticles as a
      photothermal therapy (PTT) agent for synergistic combination of chemotherapy and
      PTT as well as overcoming the drawbacks of quercetin. Moreover, folic acid-bovine
      serum albumin (FA-BSA) conjugates are applied to stabilize the CuS@ZIF-8-QT to
      promote the bioavailability of quercetin and realize active-targeting drug
      delivery. Near-infrared (NIR) fluorescent imaging demonstrated the highly
      increased drug accumulations of FA-BSA/CuS@ZIF-8-QT in tumors, resulting from
      efficient internalization via FA-receptors-mediated endocytosis. The results of
      in vivo and in vitro anticancer experiments demonstrate that quercetin and PTT
      agent can work together efficiently under NIR irradiation, thus remarkably
      improving the anticancer effect. Therefore, our newly designed FA-BSA/CuS@ZIF-8
      QT multifunctional drug delivery system might be a promising nanoplatform for
      cancer treatment.

PMID- 30215255
TI  - In Vitro Mechanistic Study of the Anti-inflammatory Activity of a Quinoline
      Isolated from Spondias pinnata Bark.
AB  - The search for new plant-based anti-inflammatory drugs continues in order to
      overcome the detrimental side effects of conventional anti-inflammatory agents,
      both steroidal and nonsteroidal. This study involves the quinoline SPE2, 7
      hydroxy-6-methoxyquinolin-2(1 H)-one, isolated from the EtOAc fraction of
      Spondias pinnata bark. Structure elucidation was done using analytical
      spectroscopic methods including Fourier transform infrared spectroscopy, high
      resolution electrospray ionization mass spectrometry, nuclear magnetic resonance
      spectroscopy, and single-crystal X-ray crystallography. The anti-inflammatory
      activity of SPE2 was evaluated in a lipopolysaccharide (LPS)-stimulated murine
      macrophage RAW 264.7 model. SPE2 effectively suppressed LPS-induced
      overproduction of pro-inflammatory mediators such as nitric oxide (NO), tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta, and reactive
      oxygen species. Expression levels of NO synthesizing enzyme, cyclooxygenase-2,
      TNF-alpha, IL-6 and IL-1beta were also determined to return to normal after SPE2
      treatment. Localization of NF-kappaB was evaluated by confocal microscopy and
      Western blotting, which showed a dose-dependent reduction of NF-kappaB inside the
      nucleus and an increase in cytoplasmic NF-kappaB with SPE2 treatment.
      Collectively, the results suggest that SPE2 has anti-inflammatory activity via
      inhibition of NF-kappaB activation.

PMID- 30215257
TI  - Poly(allyl alcohol) Homo- and Block Polymers by Postpolymerization Reduction of
      an Activated Polyacrylamide.
AB  - Direct polymerization of allyl alcohol generally results in low molar mass
      oligomers or highly branched or cross-linked structures, and the properties and
      applications of linear, high molar mass poly(allyl alcohol) (PAA) are relatively
      unexplored. Such macromolecular materials that cannot otherwise be obtained
      directly can be accessed by postpolymerization modification strategies. Herein we
      describe the synthesis and characterization of linear, high molar mass PAA by
      borohydride reduction of a new activated polyacrylamide. The facile
      polymerization and mild reduction conditions enable the preparation of PAA of
      targeted molar masses and low dispersity, as well as PAA block polymers via
      chemoselective reduction of the activated amide moiety.

PMID- 30215256
TI  - Necklace-like Multishelled Hollow Spinel Oxides with Oxygen Vacancies for
      Efficient Water Electrolysis.
AB  - The durability and reactivity of catalysts can be effectively and precisely
      controlled through the careful design and engineering of their surface structures
      and morphologies. Herein, we develop a novel "adsorption-calcination-reduction"
      strategy to synthesize spinel transitional metal oxides with a unique necklace
      like multishelled hollow structure exploiting sacrificial templates of
      carbonaceous microspheres, including NiCo2O4 (NCO), CoMn2O4, and NiMn2O4.
      Importantly, benefiting from the unique structures and reduction treatment to
      offer rich oxygen vacancies, the unique reduced NCO (R-NCO) as a bifunctional
      electrocatalyst exhibits the dual characteristics of good stability as well as
      high electrocatalytic activity for both the hydrogen evolution reaction (HER) and
      oxygen evolution reaction (OER). At 1.61 V cell voltage, a 10 mA cm-2 water
      splitting current density is obtained from the dual-electrode, alkaline water
      electrolyzer. Calculations based on density functional theory (DFT) reveal a
      mechanism for the promotion of the catalytic reactions based on a decrease in the
      energy barrier for the formation of intermediates resulting from the introduction
      of oxygen vacancies through the reduction process. This method could prove to be
      an effective general strategy for the preparation of complex, hollow structures
      and functionalities.

PMID- 30215259
TI  - Low-Temperature Surface Forces Apparatus to Determine the Interactions between
      Ice and Silica Surfaces.
AB  - We have developed a low-temperature surface forces apparatus (SFA) using a
      thermoelectric Peltier module inserted below the bottom surface of the lower
      sample holder, giving easy access to the samples and allowing quick temperature
      changes. In air, the temperature can be decreased to ca. -20  degrees C. To
      demonstrate the performance of the apparatus, we measured the interactions
      between ice and a silica surface at -11.5 +/- 0.5  degrees C. An exponentially
      decaying repulsion of the decay length, 11.2 +/- 1.0 nm, was observed, and
      attributed to the electric double layer (EDL) repulsion. The surface potential of
      the ice was calculated to be -35 mV by fitting the data to the EDL model.

PMID- 30215258
TI  - Discovery of ( S)-3-(3-(3,5-Dimethyl-1 H-pyrazol-1-yl)phenyl)-4-(( R)-3-(2
      (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a
      Nonpeptidic alphavbeta6 Integrin Inhibitor for the Inhaled Treatment of
      Idiopathic Pulmonary Fibrosis.
AB  - A series of 3-aryl(pyrrolidin-1-yl)butanoic acids were synthesized using a
      diastereoselective route, via a rhodium catalyzed asymmetric 1,4-addition of
      arylboronic acids in the presence of ( R)-BINAP to a crotonate ester to provide
      the ( S) absolute configuration for the major product. A variety of aryl
      substituents including morpholine, pyrazole, triazole, imidazole, and cyclic
      ether were screened in cell adhesion assays for affinity against alphavbeta1,
      alphavbeta3, alphavbeta5, alphavbeta6, and alphavbeta8 integrins. Numerous
      analogs with high affinity and selectivity for the alphavbeta6 integrin were
      identified. The analog ( S)-3-(3-(3,5-dimethyl-1 H-pyrazol-1-yl)phenyl)-4-(( R)-3
      (2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid
      hydrochloride salt was found to have very high affinity for alphavbeta6 integrin
      in a radioligand binding assay (p Ki = 11), a long dissociation half-life (7 h),
      very high solubility in saline at pH 7 (>71 mg/mL), and pharmacokinetic
      properties commensurate with inhaled dosing by nebulization. It was selected for
      further clinical investigation as a potential therapeutic agent for the treatment
      of idiopathic pulmonary fibrosis.

PMID- 30215260
TI  - A Comprehensive Screening of Escherichia coli Isolates from Scandinavia's Largest
      Sewage Treatment Plant Indicates No Selection for Antibiotic Resistance.
AB  - There is concern that sewage treatment plants (STPs) serve as hotspots for
      emergence and selection of antibiotic resistant bacteria. However, field studies
      investigating resistance selection by comparing bacterial populations in
      influents and effluents have produced variable and sometimes contradictive
      results. Also, large taxonomic changes between influents and effluents make
      interpretation of studies measuring relative gene abundances ambiguous. The aim
      here was to investigate whether within-species selection occurs by conducting a
      comprehensive screening of Escherichia coli isolated from composite influent and
      effluent samples collected at Scandinavia's largest STP, accompanied by analyses
      of antibiotics residues. In total, 4028 isolates, collected on eight occasions
      during 18 months, were screened for resistance to seven antibiotics. Although
      differences in proportions of resistant E. coli between influent and effluent
      samples were detected for a few antibiotics on two occasions, aggregated data
      over time showed no such differences for any of the investigated antibiotics.
      Neither was there any enrichment of multiresistant or extended-spectrum beta
      lactamase-producing isolates through the treatment process. Despite some
      antibiotics were detected at or close to concentrations predicted to provide some
      selective pressure, field observations of resistance profiles in E. coli do not
      provide support for systematic selection in the investigated STP.

PMID- 30215261
TI  - LC-MS/MS bioanalysis of plasma 1, 14-tetradecanedioic acid and 1, 16
      hexadecanedioic acid as candidate biomarkers for organic anion-transporting
      polypeptide mediated drug-drug interactions.
AB  - AIM: A robust LC-MS/MS assay was developed to quantify endogenous 1, 14
      tetradecanedioic acid (TDA) and 1, 16-hexadecanedioic acid (HDA) in human plasma
      as potential biomarkers for evaluating drug-drug interactions mediated by the
      hepatic drug transporters, organic anion-transporting polypeptides. RESULTS: This
      assay was validated using fit-for-purpose approach over standard curve range of
      2.5-1000 nM for TDA and HDA using analyte-free charcoal-stripped human plasma as
      the surrogate matrix. Chromatographic separation condition was successfully
      optimized to separate TDA from an interference peak while maintaining both
      analytes in neutral forms to minimize carryover issue. CONCLUSION: The described
      assay is currently applied to a clinical study for evaluating TDA/HDA as
      potential substitute biomarkers for drug-drug interaction studies.

PMID- 30215262
TI  - Anal Microbial Patterns and Oncogenic Human Papillomavirus in a Pilot Study of
      Nigerian Men Who Have Sex with Men at Risk for or Living with HIV.
AB  - To cluster anal microbiota and define microbial patterns associated with
      biological, clinical, and behavioral correlates among Nigerian men who have sex
      with men (MSM) living with or at risk for HIV. In this cross-sectional pilot
      study, the 15 most abundant 16S taxa in the anal microbiota of 113 MSM underwent
      unsupervised K-means clustering and z-score comparisons to define similarities
      and dissimilarities among 4 microbiota taxonomic profiles. Distributions of
      oncogenic HPV (high-risk human papillomavirus [HR-HPV]), concurrent HIV,
      antiretroviral therapy (ART), and other clinical and behavioral data were
      evaluated using Fisher's exact and Kruskal-Wallis tests to determine biological
      signatures of cluster membership. Prevotella was consistently represented in each
      cluster, but the average composition ranged from 14% to 44%. Cluster 2 was
      enriched with a member of the Fusobacteria phylum, Sneathia (29%). More
      participants of cluster 2 were HIV infected and taking ART (83%, 5/6), were
      virally suppressed (80%, 4/5), had HPV-16 (66.7%, 4/6), and reported no vaginal
      sex partners (83%, 5/6). HPV-35, a highly prevalent oncogenic HPV in Nigeria, was
      observed in all clusters except cluster 2 (0%, 0/6). Other covariates were
      similar across clusters (all p > .05). K-means unsupervised clustering, a
      canonical pattern recognition method, generalized the microbial community
      composition and structure while accounting for among sample variability. Further
      studies are needed to evaluate whether an anal microbial community enriched with
      members of the Fusobacteria phylum is associated with HIV-infected MSM who are
      virally suppressed and have a concurrent HPV-16.

PMID- 30215263
TI  - Expanding Understanding of Community Health Worker Programs: A Cross-Sectional
      Survey on the Work, Satisfaction, and Livelihoods of CHWs in Madagascar.
AB  - With health worker shortages in rural areas, community health workers (CHWs) are
      instrumental to the sustainability of primary health care and to the ability to
      meet health needs. Identifying appropriate operational models and incentive
      structures is an important element of long-term success. This article reports on
      CHWs' work demands and affective response to their volunteer work within the
      broader context of their livelihoods in Madagascar. A cross-sectional survey of
      874 CHWs, called Agents de Sante Communautaire (ACs), from 14 districts across 5
      regions was conducted in June 2015. Only 44% of ACs had cash savings. Subsistence
      farming was the main livelihood strategy; ninety-two percent of ACs were food
      insecure and 89% had experienced a shock in the past year. Overall, 77% of ACs
      financed commodity resupply through sales of health products and 18% from their
      personal savings; stock-outs at point of supply and financial and time
      constraints were the main reported challenges in getting health products. The
      average satisfaction score with AC work was 3 out of 4. This assessment from
      Madagascar helps unveil a more comprehensive view of the reality of CHWs' lives.
      Managers need to take into account the potential implications of the demands of
      CHW work on already precarious livelihoods.

PMID- 30215264
TI  - Role of microRNA-126 in vascular cognitive impairment in mice.
AB  - Vascular dementia (VaD) affects cognition and memory. MicroRNA-126 (miR-126) is
      an angiogenic microRNA that regulates vascular function. In this study, we employ
      a multiple microinfarction (MMI) model to induce VaD in mice, and investigate VaD
      induced cognitive dysfunction, white matter (WM) damage, glymphatic dysfunction
      and the role of miR-126 in mediating these effects. Male six-to eight-months old
      C57/BL6 mice (WT) were subject to MMI model, and cerebral blood flow (CBF),
      vessel patency, glymphatic function, cognitive function, and serum miR-126
      expression were measured. Mice were sacrificed at 28 days after MMI. To
      investigate the role of miR-126 in VaD, cognitive function, water channel
      integrity and glymphatic function were assessed in male, six-to eight months old
      conditional-knockout endothelial cell miR-126 (miR-126EC-/-), and control (miR
      126fl/fl) mice. MMI in WT mice induces significant cognitive deficits, decreases
      CBF and vessel patency; evokes astrocytic and microglial activation, increases
      inflammation, axonal/WM damage; decreases synaptic plasticity and dendritic spine
      density, instigates water channel and glymphatic dysfunction, and decreases serum
      miR-126 expression. MiR-126EC-/- mice exhibit significant cognitive impairment,
      decreased CBF, myelin density and axon density, increased inflammation, and
      significant water channel and glymphatic dysfunction compared to miR-126fl/fl
      mice. Reduction of endothelial miR-126 expression may mediate cognitive
      impairment in MMI-induced VaD.

PMID- 30215265
TI  - Health-Related Quality of Life and Work Productivity of Adults With ADHD: A U.K.
      Web-Based Cross-Sectional Survey.
AB  - OBJECTIVE: The objective of this study was to assess health-related quality of
      life (HRQoL) in adult ADHD. METHOD: U.K. residents aged 18 to 55 years with ADHD
      and no major mental health comorbidities completed an online survey of disorder
      history, the EuroQoL 5-Dimensions 5-Level (EQ-5D-5L), and the Work Productivity
      and Activity Impairment Questionnaire: General Health (WPAI:GH). ADHD Rating
      Scale-IV (ADHD-RS-IV) score was assessed by telephone. RESULTS: In total, 233
      participants completed the study (mean age 32.6 years; 65.2% women). Mean ( SD)
      ADHD-RS-IV total score, EQ-5D utility, and visual analog scale (VAS) scores were
      43.5 (7.88), 0.74 (.21), and 69.8 (17.76), respectively. Mean ( SD) WPAI:GH
      scores indicated that health problems caused 45.7% (29.9) overall work impairment
      and 45.8% (28.9) impairment in regular daily activities. Greater work and
      activity impairment were both significantly independently associated with lower
      utility after adjusting for age, gender, and somatic comorbidities. CONCLUSION:
      Adult ADHD impairs HRQoL, work productivity, and regular daily activities.

PMID- 30215266
TI  - External Quality Assessment Scheme for HIV-1 Drug-Resistance Genotyping in
      Thailand.
AB  - The efficacy of antiretroviral (ARV) therapy can be compromised by the emergence
      and transmission of HIV-1 drug-resistant strains. HIV-1 drug-resistance (DR)
      genotypic testing thus plays an important role in the selection of optimal
      treatment regimens for HIV-infected individuals. Given the complexities of the
      testing procedures and the variety of approaches used, there is considerable
      potential for results to vary between laboratories. In Thailand, the national
      External Quality Assessment (EQA) scheme assesses the DR genotype testing
      performance of laboratories. Here, we evaluated the performance of laboratories
      in nucleotide sequencing and compared drug-resistance-associated mutations (DRMs)
      in the HIV-1 protease (PR) and reverse transcriptase (RT) genes during 2010-2015.
      The EQA samples in the 12 panels showed predominance for the CRF01_AE (85%) and
      subtype B (15%). Fourteen laboratory datasets were generated: eight using TruGene
      (TG), two using ViroSeq (VS), and four using in-house (IH) assays. All IH and VS
      laboratories had penalty scores <7, whereas five of the eight TG laboratories had
      fluctuating penalty scores. Moreover, seven and six TG laboratories could not
      amplify the two identical samples, 10B and 10E samples, or the CRF01_AE. Our
      findings demonstrate the requirement for laboratory participation in the ongoing
      EQA program and the optimization of kit assays using CRF01_AE samples. Our
      results also indicate that one advantage of participation is that the
      laboratories can monitor and investigate the source of laboratory errors.

PMID- 30215267
TI  - Dried Blood Spots Stored at Room Temperature Should Not Be Used for HIV Incidence
      Testing.
AB  - The limiting antigen (LAg)-avidity assay is a serologic assay used for cross
      sectional HIV incidence testing. We compared the results obtained with the LAg
      avidity assay using dried blood spot (DBS) samples stored at room temperature (18
      degrees C-25 degrees C) or stored frozen at -80 degrees C with results obtained
      from matched plasma samples. Matched DBS and plasma samples (306 paired samples)
      were collected in the HIV Prevention Trials Network (HPTN) 068 trial in South
      Africa (2012-2014). The DBS were stored at room temperature before testing.
      Matched DBS and plasma samples (100 paired samples) from the Consortium for the
      Evaluation and Performance of HIV Incidence Assays (CEPHIA) were collected in
      2016 and were stored at -80 degrees C. All DBS testing was performed in 2017.
      Differences in normalized optical density (ODn) were compared between matched DBS
      and plasma samples. For DBS samples stored at room temperature (HPTN 068), the
      average difference in ODn values for plasma versus DBS was 1.49 (95% confidence
      intervals [CI]: 1.36-1.62). In contrast, when DBS samples were stored at -80
      degrees C (CEPHIA), the average difference in ODn values for plasma versus DBS
      was -0.22 (95% CI: -0.32 to -0.13). DBS samples stored at room temperature should
      not be used for cross-sectional HIV incidence testing with the LAg-avidity assay.

PMID- 30215268
TI  - A Window Into the HIV Epidemic from a South African Emergency Department.
AB  - The aim of the study was to describe the HIV care continuum in emergency
      department (ED) patients in the Eastern Cape region of South Africa. This is a
      cross-sectional, identity-unlinked serosurvey, whereby discarded/excess samples
      from all patients who had blood drawn during the study period for routine care
      and sufficient serum remaining were tested for HIV, hepatitis B virus, and
      hepatitis C virus infection; HIV viral load (VL); and presence of antiretroviral
      (ARV) drugs. We also estimated cross-sectional incidence using the Limiting
      Antigen Avidity assay and HIV VL. The study was conducted between September and
      November 2016 at the Frere Hospital Emergency Department in East London, South
      Africa. The overall HIV prevalence in our study population was 26.9% [95%
      confidence interval (CI): 25.0-28.8; n = 2,100]. The highest prevalence was
      observed among females in the 30-39 years age group [60.3% (95% CI: 53.2-67.1)].
      HIV prevalence was significantly higher among females compared with males in both
      the 20-29 years age group and 30-39 years age group (p < .05), but nearly
      identical to older age groups. ARV drugs were detected in 53.5% (95% CI: 48.1
      58.9) of HIV-infected subjects. The frequency of HIV viral suppression (< 1,000
      copies/mL) was 48.5% (95% CI: 44.3-52.7), and was not statistically different
      between males and females (age-adjusted prevalence ratio = 1.15, 95% CI: 0.95
      1.39). The HIV incidence rate was estimated to be 2.6% (95% CI: 1.2-3.9). The
      Frere Hospital ED has an extremely high burden of HIV infection. The detection of
      ARV drugs and prevalence of viral suppression fall short of the World Health
      Organization 90-90-90 goals in this population. Furthermore, there were a large
      number of patients with recent infection in the ED. The ED is a critical venue
      for testing and linkage to care of high-yield population who are likely missed by
      current testing and linkage-to-care programs.

PMID- 30215269
TI  - Comparison between methadone and buprenorphine within the QUAD protocol for
      perioperative analgesia in cats undergoing ovariohysterectomy.
AB  - Objectives The aim of this study was to investigate the analgesic efficacy of
      methadone vs buprenorphine within the QUAD protocol for anaesthesia in cats
      undergoing ovariohysterectomy. Methods One hundred and twenty cats were recruited
      to an assessor-blinded, randomised clinical trial. Cats received either methadone
      (5  mg/m2) or buprenorphine (180  ug/m2) combined with ketamine, midazolam and
      medetomidine intramuscularly. Anaesthesia was maintained with isoflurane in
      oxygen. Atipamezole was administered at extubation. Pain was assessed using the
      feline Composite Measure Pain Scale (CMPS-F), a dynamic interactive visual
      analogue scale (DIVAS) and mechanical nociceptive threshold (MNT). Sedation,
      pain, heart rate and respiratory rate were measured prior to QUAD administration,
      before intubation, and 2, 4, 6 and 8 h post-QUAD administration. If indicated by
      the CMPS-F, rescue analgesia was provided with 0.5 mg/kg of methadone
      administered intramuscularly. Meloxicam was administered after the last
      assessment. Differences in pain scores between groups were compared using a two
      way repeated-measures ANOVA and requirement for rescue analgesia was compared
      using a chi2 test. Results Cats administered methadone had lower CMPS-F scores
      over time ( P = 0.04). Eighteen of 60 cats required rescue analgesia in the
      methadone group vs 29/60 in the buprenorphine group ( P = 0.028). All cats that
      received rescue analgesia required it within 6 h post-QUAD administration. There
      were no differences between groups in MNT or pain measured using the DIVAS.
      Conclusions and relevance Methadone produced clinically superior postoperative
      analgesia for the first 8 h after neutering than buprenorphine when used within
      the QUAD protocol.

PMID- 30215270
TI  - Flow cytometry in cell-based pharmacokinetics or cellular kinetics in adoptive
      cell therapy.

PMID- 30215271
TI  - Synthesis, molecular modeling and biological screening of some pyrazole
      derivatives as antileishmanial agents.
AB  - AIM: Novel open chain and cyclized derivatives containing pyrazole scaffold were
      designed, synthesized and evaluated as antileishmanial compounds. Methodology &
      results: In silico reverse docking experiment suggested Leishmania major
      pteridine reductase (Lm-PTR1) as a putative target for the synthesized compounds.
      In vitro antileishmanial screening against L. major promastigotes and amastigotes
      using miltefosine and amphotericin B as references showed that the majority of
      the compounds displayed activity higher than miltefosine. Compounds 3i and 5
      showed the highest antileishmanial activity with IC50 values of 1.45 +/- 0.08 MUM
      and 2.30 +/- 0.09 MUM, respectively, for the amastigote form. In silico drug
      likeness and toxicity predictions showed acceptable profiles for most of the
      compounds, which were validated by experimental toxicity studies. CONCLUSION:
      This study offers promising entities for antileishmanial activity.

PMID- 30215273
TI  - Effects of Mindfulness-Based Psychoeducation on the Internalized Stigmatization
      Level of Patients With Schizophrenia.
AB  - The aim of this study was to determine the effects of mindfulness-based
      psychoeducation on internalized stigma in patients with schizophrenia. The
      patients were recruited from the community mental health centers. This
      quasiexperimental study was conducted using pretests and posttests with a control
      group. The participants were 69 patients with schizophrenia; 34 were part of the
      experimental group and 35 were part of the control group. The patients in the
      experimental group participated 2 days a week for 6 weeks in a total of 12
      sessions which were given in the form of face-to-face group training. The
      difference between the scale mean posttest scores of the patients in the
      experimental and control groups was found to be statistically significant ( p <
      .05). In the intragroup comparisons, a significant difference was found between
      the stigma mean scores in the experimental group ( p < .05). It was concluded
      that mindfulness-based psychoeducation was effective in reducing stigma in
      patients with schizophrenia.

PMID- 30215272
TI  - Omental Pouch Technique for Combined Site Islet Autotransplantation Following
      Total Pancreatectomy.
AB  - Total pancreatectomy and islet autotransplantation (TPIAT) is an effective
      treatment for selected patients with chronic pancreatitis. The portal circulation
      is the standard infusion site for islet transplant, but marked elevation of
      portal pressures may prevent complete islet infusion. Herein we report a novel
      technique of combined site islet autotransplantation using an omental pouch. This
      technique may be useful when technical limitations prevent complete intraportal
      transplantation. In four TPIAT recipients with intraoperative issues precluding
      the complete intraportal infusion of islets, an omental pouch was created to
      contain the remaining islet mass. Patients were monitored for complications, and
      islet graft function was assessed using mixed meal tolerance testing and compared
      with matched controls who received only intraportally transplanted islets. All
      patients had decreasing insulin requirements as their recovery progressed. At 3
      months follow-up there were no significant differences in glycemic control or
      graft function for the combined site recipients compared with their matched
      controls who only received an intraportal islet infusion. The omentum has
      potentially desirable qualities such as accessibility, capacity, and
      systemic/portal vascularity comparable to the native pancreas. The omental pouch
      technique may represent a safe and effective alternate site for islet
      autotransplantation. Further study is needed to confirm these findings.

PMID- 30215274
TI  - Turning Plasmodium survival strategies against itself.

PMID- 30215275
TI  - Diabetic retinopathy: how far are we from personalized medicine?

PMID- 30215276
TI  - Guardians of the Living Water: Using a Health Literacy Framework to Evaluate a
      Child as Change Agent Intervention.
AB  - BACKGROUND: American Indian communities in the United States experience
      considerable health inequities, including increased exposure to environmental
      contaminants. Consequently, community members of the Apsaalooke (Crow) Nation
      identified the lack of water-related environmental knowledge among children as an
      area of concern. AIM: The purpose of this study was to provide a feasibility
      evaluation of an increasingly sophisticated environmental health literacy program
      for children. METHOD: A community-academic partnership developed and piloted the
      Guardians of the Living Water program to increase environmental health literacy
      among children and their families on the Crow reservation. Nutbeam's framework
      for health literacy, a schema based on functional, interactive, and critical
      literacy, shaped the program evaluation. We used a within-subjects, quasi
      experimental design without a control group. Interviews with children and parents
      were used to assess the feasibility of the program, while pre-/posttests assessed
      changes in knowledge, skills, and behavior. RESULTS: Compared with
      preintervention responses, those from postintervention indicated significant
      increases for selected knowledge and attitude components. Based on qualitative
      interviews with children and caregivers, the camp was a valuable experience and
      increased knowledge of water quality science and reinforced cultural knowledge.
      DISCUSSION: This success of our program stems from the trust initially built
      between partners and then expanded throughout the community. The program and the
      evaluation benefited from both the health literacy framework and from our
      integration of Apsaalooke values. CONCLUSION: Our findings suggest that a
      community-based intervention designed to increase environmental health literacy
      among youth and their social networks is feasible and acceptable to this American
      Indian community.

PMID- 30215277
TI  - Pain inconsistency and sleep in mid to late-life: the role of depression.
AB  - OBJECTIVES: Inconsistency in pain may lead to depression, which may then
      influence sleep. Thus, the purpose of this study was to examine whether
      depression mediates the relationship between day-to-day inconsistency in pain and
      sleep in middle aged to older adults. METHODS: Baseline measures from the Active
      Adult Mentoring Project were used for secondary data analysis. Participants
      included 82 adults in mid- to late-life. Pain was assessed for seven consecutive
      days on an 11-point Likert-scale, with pain inconsistency defined as the seven
      day individual standard deviation. A self-report daily diary was used to assess
      sleep efficiency (SE), total wake time (TWT), total sleep time (TST), and sleep
      quality (SQ), and depression was assessed using the BDI-II. RESULTS: Mediation
      analyses revealed that depression partially mediated the relationship between
      pain inconsistency and SE, TWT, and SQ but not TST. CONCLUSIONS: Results indicate
      that depression may be an important factor through which pain inconsistency
      influences sleep. Although further research is warranted, these preliminary
      findings suggest that intervening on both pain inconsistency and depression may
      be one way to improve sleep in older adults.

PMID- 30215278
TI  - In Vitro Derivation of Functional Sertoli-Like Cells from Mouse Embryonic Stem
      Cells.
AB  - Sertoli cells (SCs) in the mammalian testes are well known as supporting cells of
      spermatogenesis, but have recently become an attractive source of cell therapy
      because of their capacity for immune modulation and trophic effects. In order to
      increase their applicable efficacy, we demonstrate a novel differentiation method
      for mouse embryonic stem cell (ESC)-derived Sertoli-like cells (SLCs) via the
      intermediate mesoderm (IM). We show that IM derived from an induction of 6 days
      expressed markers such as Wt1, Lhx1, Pax2 and Osr1, and that a sequential
      induction of 6 days resulted in ESC-SLCs. The SLCs expressed their marker genes (
      Sf1, Sox9, Gata4, Wt1, Fshr and Scf), but the pluripotency-marker gene Oct4 was
      decreased. After sorting by FSHR expression, high-purity (> 90%) SLCs were
      collected that showed distinct characteristics of SCs such as high phagocytic and
      immune modulation activities as well as the expression of immune-related genes.
      In addition, when transplanted into the seminiferous tubule of busulfan-treated
      mice, SLCs re-located and were maintained in the basal region of the tubule.
      These results demonstrated that our robust sequential differentiation system
      produced functional SLCs from mouse ESCs in vitro.

PMID- 30215279
TI  - Understanding Outcomes in Behavior Change Interventions to Prevent Pediatric
      Obesity: The Role of Dose and Behavior Change Techniques.
AB  - BACKGROUND: Behavioral interventions to prevent pediatric obesity have shown
      inconsistent results across the field. Studying what happens within the "black
      box" of these interventions and how differences in implementation lead to
      different outcomes will help researchers develop more effective interventions.
      AIM: To compare the implementation of three features of a phone-based
      intervention for parents (time spent discussing weight-related behaviors,
      behavior change techniques used in sessions, and intervention activities
      implemented by parents between sessions) with study outcomes. METHODS: A random
      selection of 100 parent-child dyads in the intervention arm of a phone-based
      obesity prevention trial was included in this analysis. Sessions were coded for
      overall session length, length of time spent discussing specific weight-related
      behaviors, number of behavior change techniques used during the sessions, and
      number of intervention-recommended activities implemented by the parents between
      sessions (e.g., parent-reported implementation of behavioral practice/rehearsal
      between sessions). The primary study outcome, prevention of unhealthy increase in
      child body mass index (BMI) percentile, was measured at baseline and 12 months.
      RESULTS: Overall session length was associated with decreases in child BMI
      percentile ( b = -0.02, p = .01). There was no association between the number of
      behavior change techniques used in the sessions and decreases in child BMI
      percentile ( b = -0.29, p = .27). The number of activities the parents reported
      implementing between sessions was associated with decreases in child BMI
      percentile ( b = -1.25, p = .02). DISCUSSION: To improve future interventions,
      greater attention should be paid to the intended and delivered session length,
      and efforts should be made to facilitate parents' implementation of intervention
      recommended activities between sessions (ClinicalTrials.gov, No. NCT01084590).

PMID- 30215280
TI  - Drug metabolism and metabolite safety assessment in drug discovery and
      development.
AB  - INTRODUCTION: Drug metabolism is one of the most important processes involving a
      drug after administration. Undesirable pharmacokinetic properties may lead to
      drug discontinuation. In the past several decades, a number of drugs have been
      withdrawn from the market due to safety issues caused by metabolites, especially
      reactive metabolites (RMs). Area covered: The focus of this review is on the role
      that drug metabolites play in drug discovery and developmental stages, with
      particular emphasis on metabolism-guided lead optimization, safety assessment of
      drug metabolites, drug-drug interaction potential of metabolites, and RMs safety
      assessment. In addition, species-related metabolic differences are briefly
      covered. Expert opinion: For the safety assessment of drug metabolites, a number
      of factors should be given full consideration, such as dose, in vitro and in vivo
      correlations, in vivo animal toxicological findings, and the accumulation of
      metabolites in plasma and/or tissues. Several factors, especially dose and
      multiple metabolic pathways, can significantly affect the occurrence of
      idiosyncratic adverse drug reactions (IADRs). Multiple assays should be used to
      assess RMs and thus avoid false-negative results. There is no clear interplay
      between the formation of RMs and the occurrence of IADRs. Avoidance of structural
      alerts and decreasing dose are the most effective strategies in reducing the risk
      of IADRs.

PMID- 30215281
TI  - Novel bacterial topoisomerase inhibitors: challenges and perspectives in reducing
      hERG toxicity.

PMID- 30215282
TI  - Improving therapeutic potential of antibacterial spider venom peptides: coarse
      grain molecular dynamics guided approach.
AB  - AIM: Spider venom is a rich source of antibacterial peptides, whose hemolytic
      activity is often excessive. METHODOLOGY: How to get rid of it? Using latarcins
      from Lachesana tarabaevi and oxyopinin Oxt 4a from Oxyopes takobius spider venoms
      we performed coarse-grained molecular dynamics simulations of these peptides in
      the presence of lipid bilayers, mimicking erythrocyte membranes. This identified
      hemolytically active fragments within Oxt 4a and latarcins. Then, we synthesized
      five 20-residue peptides, containing different parts of the Oxt 4a and latarcin-1
      sequence, carrying mutations within the identified regions. CONCLUSION: The
      antibacterial and hemolytic tests suggested that the three of the synthesized
      peptides demonstrated substantial decrease in hemolytic activity, retaining, or
      even exceeding antibacterial potential of the parent peptides.

PMID- 30215283
TI  - Select hyperacute complications of ischemic stroke: cerebral edema, hemorrhagic
      transformation, and orolingual angioedema secondary to intravenous Alteplase.
AB  - INTRODUCTION: Remarkable advances have occurred in the management of acute
      ischemic stroke, especially in regards to reperfusion treatments. With advances
      in reperfusion treatments come the risk of complications associated with these
      treatments. Areas covered: The article focuses on three acute complications that
      can occur in the setting of acute ischemic stroke: cerebral edema, hemorrhagic
      transformation, and orolingual angioedema following administration of alteplase,
      a recombinant tissue plasminogen activator. Predictors of the development of
      these complications are reviewed. The management of cerebral edema and
      hemorrhagic transformation is also reviewed in depth including potential new
      treatments targeting the blood-brain barrier. The article also reviews the
      management of the rare but potentially fatal complication of orolingual
      angioedema secondary to alteplase. Expert commentary: An understanding of the
      pathophysiology leading to the development of malignant cerebral edema and
      hemorrhagic transformation allows the clinician to anticipate and properly manage
      these acute complications. Regardless of a patient's age or comorbidities, the
      decision to pursue decompressive hemicraniectomy in patients with malignant
      cerebral edema should be based on an honest assessment of expected outcome and
      guided by the patient's prior wishes regarding an acceptable quality of life.

PMID- 30215284
TI  - A Neuronal Network Model of the Primate Visual System: Color Mechanisms in the
      Retina, LGN and V1.
AB  - Color plays a key role in human vision but the neural machinery that underlies
      the transformation from stimulus to perception is not well understood. Here, we
      implemented a two-dimensional network model of the first stages in the primate
      parvocellular pathway (retina, lateral geniculate nucleus and layer 4C[Formula:
      see text] in V1) consisting of conductance-based point neurons. Model parameters
      were tuned based on physiological and anatomical data from the primate foveal and
      parafoveal vision, the most relevant visual field areas for color vision. We
      exhaustively benchmarked the model against well-established chromatic and
      achromatic visual stimuli, showing spatial and temporal responses of the model to
      disk- and ring-shaped light flashes, spatially uniform squares and sine-wave
      gratings of varying spatial frequency. The spatiotemporal patterns of
      parvocellular cells and cortical cells are consistent with their classification
      into chromatically single-opponent and double-opponent groups, and nonopponent
      cells selective for luminance stimuli. The model was implemented in the widely
      used neural simulation tool NEST and released as open source software. The aim of
      our modeling is to provide a biologically realistic framework within which a
      broad range of neuronal interactions can be examined at several different levels,
      with a focus on understanding how color information is processed.

PMID- 30215285
TI  - Convolutional Neural Networks for Neuroimaging in Parkinson's Disease: Is
      Preprocessing Needed?
AB  - Spatial and intensity normalizations are nowadays a prerequisite for neuroimaging
      analysis. Influenced by voxel-wise and other univariate comparisons, where these
      corrections are key, they are commonly applied to any type of analysis and
      imaging modalities. Nuclear imaging modalities such as PET-FDG or FP-CIT SPECT, a
      common modality used in Parkinson's disease diagnosis, are especially dependent
      on intensity normalization. However, these steps are computationally expensive
      and furthermore, they may introduce deformations in the images, altering the
      information contained in them. Convolutional neural networks (CNNs), for their
      part, introduce position invariance to pattern recognition, and have been proven
      to classify objects regardless of their orientation, size, angle, etc. Therefore,
      a question arises: how well can CNNs account for spatial and intensity
      differences when analyzing nuclear brain imaging? Are spatial and intensity
      normalizations still needed? To answer this question, we have trained four
      different CNN models based on well-established architectures, using or not
      different spatial and intensity normalization preprocessings. The results show
      that a sufficiently complex model such as our three-dimensional version of the
      ALEXNET can effectively account for spatial differences, achieving a diagnosis
      accuracy of 94.1% with an area under the ROC curve of 0.984. The visualization of
      the differences via saliency maps shows that these models are correctly finding
      patterns that match those found in the literature, without the need of applying
      any complex spatial normalization procedure. However, the intensity normalization
      - and its type - is revealed as very influential in the results and accuracy of
      the trained model, and therefore must be well accounted.

PMID- 30215286
TI  - Effects of Brain Temperature on the Outcome of Patients with Traumatic Brain
      Injury: A Prospective Observational Study.
AB  - A prospective observational study collected temperature data from 51 patients in
      11 neurosurgical centers and follow-up outcome information at 6 months in 49
      patients. Brain temperature (Tbr) was measured directly by an intraventricular
      temperature sensor. Axillary temperature (Tax) and rectal temperature (Tre) were
      measured by electric thermometers. Tbr was 0.4 to 1.5 degrees C higher than body
      temperature. Tre correlated well with the Tbr (coefficient: 0.7378; p < 0.05).
      Among all patients, Glasgow Coma Scale (GCS) scores on admission were
      significantly lower in the patients with post-operatively extreme peak
      temperature (Tpeak, < 37 degrees C or >39 degrees C in first 24 h) and major
      temperature variation (Tvari > 1 degrees C in first 12 h; p < 0.05, p < 0.01,
      respectively). Among the patients with no temperature intervention, the extreme
      Tpeak group showed a lower Glasgow Outcome Scale-Extended (GOS-E) score at 6
      months (p < 0.05) with lower GCS scores on admission (p < 0.01), compared with
      the moderate Tpeak group. Remarkably, the major Tvari group showed significantly
      lower GOS-E scores (p < 0.05) with the same GCS scores as the minor Tvari group.
      Thus, Tre is the better candidate to estimate Tbr. Spontaneously extreme Tpeak in
      TBI represents both more serious injury on admission and worse prognosis, and
      Tvari might be used as a novel prognostic parameter in TBI. Brain temperature is
      therefore one of the critical indicators evaluating injury severity,
      prognostication, and monitoring in the management of TBI. This prospective
      observational study has been registered in ClinicalTrials.gov (
      https://clinicaltrials.gov ), and the registration number is NCT03068143.

PMID- 30215287
TI  - Extent of Spinal Cord Decompression in Motor Complete (American Spinal Injury
      Association Impairment Scale Grades A and B) Traumatic Spinal Cord Injury
      Patients: Post-Operative Magnetic Resonance Imaging Analysis of Standard
      Operative Approaches.
AB  - Although decompressive surgery following traumatic spinal cord injury (TSCI) is
      recommended, adequate surgical decompression is rarely verified via imaging. We
      utilized magnetic resonance imaging (MRI) to analyze the rate of spinal cord
      decompression after surgery. Pre-operative (within 8 h of injury) and post
      operative (within 48 h of injury) MRI images of 184 motor complete patients
      (American Spinal Injury Association Impairment Scale [AIS] grade A = 119, AIS
      grade B = 65) were reviewed to verify spinal cord decompression. Decompression
      was defined as the presence of a patent subarachnoid space around a swollen
      spinal cord. Of the 184 patients, 100 (54.3%) underwent anterior cervical
      discectomy and fusion (ACDF), and 53 of them also underwent laminectomy. Of the
      184 patients, 55 (29.9%) underwent anterior cervical corpectomy and fusion
      (ACCF), with (26 patients) or without (29 patients) laminectomy. Twenty-nine
      patients (16%) underwent stand-alone laminectomy. Decompression was verified in
      121 patients (66%). The rates of decompression in patients who underwent ACDF and
      ACCF without laminectomy were 46.8% and 58.6%, respectively. Among these
      patients, performing a laminectomy increased the rate of decompression (72% and
      73.1% of patients, respectively). Twenty-five of 29 (86.2%) patients who
      underwent a stand-alone laminectomy were found to be successfully decompressed.
      The rates of decompression among patients who underwent laminectomy at one, two,
      three, four, or five levels were 58.3%, 68%, 78%, 80%, and 100%, respectively (p
      < 0.001). In multi-variate logistic regression analysis, only laminectomy was
      significantly associated with successful decompression (odds ratio 4.85; 95%
      confidence interval 2.2-10.6; p < 0.001). In motor complete TSCI patients,
      performing a laminectomy significantly increased the rate of successful spinal
      cord decompression, independent of whether anterior surgery was performed.

PMID- 30215288
TI  - Palmitoylation controls trafficking of the intracellular Ca2+ channel
      MCOLN3/TRPML3 to regulate autophagy.
AB  - : MCOLN3/TRPML3 is a Ca2+-permeable cation channel that is expressed in multiple
      subcellular compartments with dynamic localization. Our previous studies suggest
      that upon macroautophagy/autophagy induction MCOLN3/TRPML3 is recruited and
      provides Ca2+ for the fusion process in autophagosome biogenesis. However, how
      intracellular trafficking and the Ca2+ channel function of MCOLN3/TRPML3 are
      related to autophagy are not known. Here we report that MCOLN3/TRPML3 undergoes
      palmitoylation at its C-terminal region, which is required for dynamic
      trafficking and cellular function of MCOLN3/TRPML3 in autophagy. Palmitoylation
      regulated MCOLN3/TRPML3 surface expression and trafficking, but not channel
      properties or localization and function of intracellular MCOLN3/TRPML3.
      Activation of intracellular MCOLN3/TRPML3 induced robust Ca2+ release, which
      solely increased autophagy in Ca2+- and palmitoylation-dependent manners.
      Palmitoylation regulated not only intracellular MCOLN3/TRPML3 trafficking to
      autophagic structures but also autophagic flux in induced autophagy. Importantly,
      nutrient starvation activated MCOLN3/TRPML3 to release Ca2+ and increased the
      level of MCOLN3/TRPML3 palmitoylation. Disruption of MCOLN3/TRPML3
      palmitoylation, however, abolished the starvation-induced MCOLN3/TRPML3
      activation without affecting channel activity. These results suggest that
      trafficking and channel function of MCOLN3/TRPML3 are regulated in the context of
      autophagy, and palmitoylation is a prerequisite for the function of MCOLN3/TRPML3
      as a Ca2+ channel in autophagosome formation by controlling its trafficking
      between subcellular compartments. ABBREVIATIONS: 17-ODYA, 17-octadecynoic acid; 2
      BP, 2-bromopalmitate; BFA, brefeldin A; DN, dominant-negative; GPN, glycyl-L
      phenylalanine-beta-naphthylamide; HN, hydroxylamine; KD, knockdown;
      MCOLN3/TRPML3, mucolipin 3; MS, mass spectrometry; PAT, palmitoyl
      acyltransferase; PM, plasma membrane; WT, wild type; ZDHHC, a zinc-finger motif
      and an Asp-His-His-Cys sequence.

PMID- 30215289
TI  - Fluticasone furoate/vilanterol 92/22 ug once a day: a 12-month study on outcomes
      in mild to moderate asthma.
AB  - BACKGROUND: Fluticasone furoate/vilanterol (FF/V) is an effective long-acting
      beta2 agonist/inhaled corticosteroid combination for managing persistent
      bronchial asthma. The aim of the study was to assess the outcomes achievable in
      patients with mild to moderate asthma receiving FF/V 92/22 ug once daily for 12
      months. METHODS: Data were automatically and anonymously obtained from the
      institutional database: forced expiratory volume in 1 s predicted values; the
      exacerbation and hospitalization rates; days of hospitalization; general
      practitioner (GP) or specialist visits; days of inactivity; courses of systemic
      steroids or antibiotics were recorded at baseline and after 3, 6 and 12 months of
      treatment. The overall adherence to treatment was also calculated. Analysis of
      variance was used for checking the trends of variables. The improvement in lung
      function was significant ( p < 0.001) and time dependent. The mean (+/-standard
      error) exacerbation rate per patient changed from 1.05 (+/-0.16) at baseline to
      0.28 (+/-0.07) after 3 months, 0.33 (+/-0.08) after 6 months and 0.18 (+/-0.08)
      after 12 months ( p < 0.001). The mean hospitalization rate per patient changed
      from 0.30 (+/-0.07) at baseline to 0.08 (+/-0.04) after 3 months, 0.10 (+/-0.05)
      after 6 months and 0.03 (+/-0.03) after 12 months ( p < 0.001). Also mean
      duration of hospitalization and days of inactivity were reduced over time ( p <
      0.001). GP visits were also reduced, together with specialist visits (both p <
      0.001). Steroid and antibiotic courses dropped significantly ( p < 0.001 and p <
      0.001, respectively). Moreover, changes in all outcomes considered proved time
      dependent, particularly over the second semester. Finally, over time, adherence
      to treatment was high. CONCLUSIONS: The once-daily inhalation of combined FF/V
      92/22 ug optimized systematically the exacerbation and hospitalization rates in
      mild to moderate asthma, together with all other outcomes over time. The
      effectiveness of FF/V 92/22 ug once daily proved to be time dependent over the
      period of the study.

PMID- 30215290
TI  - Body-specific influences on performance evaluation in realistic dynamic scenes.
AB  - According to the body-specificity hypothesis, left-handers (right-handers) are
      more likely to associate positive attributes with the left (right) side. We
      tested whether such body-specific influences also apply to evaluative judgments
      in realistic dynamic scenes. In two experiments (order counterbalanced), N = 231
      participants watched videos from dual mogul competition where two skiers turn
      downhill through moguls side by side simultaneously and then comparatively rated
      the skiers' technical performances. Experiments differed in the required response
      mode only. In Exp. 1, participants made forced-choice decisions by selecting
      either the left or right skier as the better performer; in Exp. 2 graded
      judgments were made on a 10-point scale ranging from -5 (skier on the left side)
      to + 5 (skier on the right side). Body-specific associations were found in Exp. 1
      (OR = 3.16), but not in Exp. 2 (OR = 1.50). A control experiment (Exp. 3; same
      participants) revealed that our sample (OR = 2.31) behaved similar to previously
      reported samples in a well-established cartoon character task, thereby confirming
      body-specific associations in our sample on a task with abstract static stimuli.
      Collectively, body-specific associations seem to apply to realistic dynamic
      scenes, particularly when frugal forced-choice decisions are required.

PMID- 30215291
TI  - Antiaging Effects of Urolithin A on Replicative Senescent Human Skin Fibroblasts.
AB  - Although the health benefits attributed to urolithin A, such as anticancer, anti
      inflammatory, and antioxidant effects, are based on numerous, diverse studies
      carried out in vitro, the biological effects of urolith A are still not entirely
      understood. In this study, we explored the biological effects of urolithin A
      using senescent human skin fibroblasts (HSFs) to determine whether urolithin A
      has any antiaging potential. Our results showed that urolithin A significantly
      increased type I collagen expression and reduced matrix metalloproteinase 1 (MMP
      1) expression. Urolithin A also reduced intracellular reactive oxygen species,
      which may be partially due to activation of the Nrf2-mediated antioxidative
      response. These results indicate that urolithin A is a promising antiaging agent.
      Meanwhile, we noticed that the 50 MUM urolithin A could cause changes in cell
      morphology and inhibition in cell proliferation, which were due to cell cycle
      arrest in G2/M phase. However, SA-beta-gal (senescence-associated beta
      galactosidase) staining and gammaH2AX immunofluorescence staining showed cellular
      senescence status of HSFs did not change. Results of DAPI (4'6-diamidino-2
      phenylindole) staining (no significant change) increased BCL2 gene expression and
      mitochondrial membrane potential (no significant change) after urolithin A
      treatment showed that the cells did not undergo apoptosis. These results provided
      further insights into the molecular mechanism of urolithin A. In conclusion,
      urolithin A showed a strong potential of antiaging.

PMID- 30215292
TI  - Pleiotropic Effects of French Maritime Pine Bark Extract to Promote Healthy
      Aging.
AB  - Extension of the healthy life span is of primary importance for the aging
      society. Among exercise, healthy nutrition, and mental training, food supplements
      are widely used as preventive measures to postpone the diverse symptoms of aging.
      The extract from the bark of the French maritime pine, Pycnogenol, rich on
      flavonoids, has anti-inflammatory and antioxidative property, proven in in vivo
      studies. The extract reduces oxidative stress and improves endothelial health.
      Its antithrombotic properties are based on inhibition of platelet aggregation. In
      double-blind, placebo-controlled clinical studies, Pycnogenol shows diverse
      positive effects. With respect to cardiovascular symptoms, the extract has an
      antihypertensive effect, slows down the progression of atherosclerosis, and
      prevents venous thrombosis. As reported in studies in China and the United
      States, type 2 diabetes and diabetic retinopathy is improved with Pycnogenol. The
      extract restores mobility of seniors in case of patients suffering from
      osteoarthritis, Pycnogenol reduces pain and stiffness and use of analgesics.
      Furthermore, cognitive functions of elderly people, especially spatial memory,
      are significantly ameliorated. Climacteric symptoms are significantly alleviated
      by the pine bark extract. Urinary symptoms of benign prostatic hyperplasia are
      reduced by Pycnogenol. In combination with l-arginine, Pycnogenol restores
      erectile function in men with erectile dysfunction. The sum of these positive
      effects on relevant symptoms of aging suggests using Pycnogenol for a more
      extended period of healthy aging.

PMID- 30215294
TI  - Campus Sexual Assault: Forging an Action-Focused Research Agenda.
AB  - In recent years, the problem of campus-based sexual assault has emerged as a
      prominent matter of concern for institutions of higher education. Amid expanded
      media attention and a shifting policy landscape, many institutions have grappled
      with programmatic and legal challenges related to systems of investigation and
      adjudication of sexual assault cases. Meanwhile, many have worked to develop and
      deploy proactive preventive measures including those involving bystander
      engagement, peer-driven interventions, sexual assault awareness campaigns, self
      defense programs, and the innovative use of social media and other technology. In
      this context, there is a growing need for high-quality empirical research that
      can shed light on the extent and nature of campus sexual assault; evaluate
      existing institutional systems and processes; and promote the development,
      testing, and evaluation of novel approaches that respond to unmet needs and
      challenges. As an introduction to a special journal issue devoted to this nascent
      but rapidly emerging field of inquiry, this article offers context and
      perspective on the vital role that research can play in the development and
      advancement of effective policies and strategies to prevent and effectively
      respond to campus-based sexual assault.

PMID- 30215295
TI  - Therapeutic effect of a xeno-free three-dimensional stem cell mass in a hind limb
      ischemia model.
AB  - This study developed a xeno-free (XF) spherical cell cluster of adipose-derived
      stem cells (hASCs) for the treatment of severe ischemic diseases. hASCs are an
      attractive cell source for therapeutic angiogenesis. Herein, we describe an
      innovative method of culturing a three-dimensional stem cell mass (3DCM) in the
      XF condition and demonstrate the therapeutic potential and safety of XF-3DCMs in
      ischemic mice and in SCID/ BALB/c Slc-nu/nu nude mice, respectively. XF-3DCMs
      were generated by culturing hASCs on a maltose-binding protein-linked basic
      fibroblast growth factor-immobilized polystyrene surface. XF-3DCMs produced
      comparable amounts of angiogenic factors such as basic fibroblast growth factor,
      vascular endothelial growth factor, and interleukin-8 compared to 3DCMs formed in
      media containing fetal bovine serum (FBS-3DCMs). The majority of the mice
      injected with XF-3DCMs exhibited limb salvaging and displayed similar blood
      perfusion compared to normal limbs. To a similar degree as for FBS-3DCMs, XF
      3DCMs enhanced therapeutic efficacy by increasing blood vessel regeneration,
      attenuating muscle degeneration and fibrosis, and facilitating the implantation
      of injected cells into host vessels. Further, the soft agar colony forming assay
      and in vivo tumorigenicity analysis showed that XF-3DCMs did not transform into
      tumor cells. No side effects were observed, including hematological and
      immunological toxicity, in mice injected with XF-3DCMs. These results suggest
      that XF-3DCMs show angiogenic and therapeutic efficacy in critical limb ischemia
      in mice and eliminate the safety problem of animal-derived material
      contamination, which is a prerequisite for clinical applications.

PMID- 30215293
TI  - Spinal Progenitor-Laden Bridges Support Earlier Axon Regeneration Following
      Spinal Cord Injury.
AB  - IMPACT STATEMENT: Spinal cord injury (SCI) results in loss of tissue innervation
      below the injury. Spinal progenitors have a greater ability to repair the damage
      and can be injected into the injury, but their regenerative potential is hampered
      by their poor survival after transplantation. Biomaterials can create a cell
      delivery platform and generate a more hospitable microenvironment for the
      progenitors within the injury. In this work, polymeric bridges are used to
      deliver embryonic spinal progenitors to the injury, resulting in increased
      progenitor survival and subsequent regeneration and functional recovery, thus
      demonstrating the importance of combined therapeutic approaches for SCI.

PMID- 30215296
TI  - Core-Shell Biphasic Microspheres with Tunable Density of Shell Micropores
      Providing Tailorable Bone Regeneration.
AB  - Unlike the conventional porous scaffolds, which have continuous three-dimensional
      porous architecture and mechanical support, the macroscopic pore structures of
      bioceramic granules-that is, the void space among closely packed granules-are of
      very limited porosity. Furthermore, it is difficult to adjust the biodegradation
      and bioactive ion release sufficiently to stimulating new bone ingrowth during
      the early stage after implantation. In this study we demonstrate a new strategy
      for selectively tailoring the porous microstructures of specific component in the
      core-shell biphasic microspheres (~2 mm in diameter) composed of 4% strontium
      substituted calcium silicate (CSi-Sr4) and beta-tricalcium phosphate (CaP). Our
      method uses rapidly gelling microspheres derived from bi-flows of alginate-loaded
      CaP and CSi-Sr4 slurries through the coaxially aligned nozzles, and collected
      using chitosan solution. When 15 MUm diameter polystyrene (PS) microspheres are
      premixed into the CaP slurry with a PS/CaP ratio (x; x% = 0%, 15%, 30%, and 45%),
      the micropores can be tailored in the CaP-shell layer after sintering, and as a
      result the biodegradation of both CSi core and CaP shell in CSi-Sr4@CaP-px
      microspheres could be adjusted simultaneously. The critical-sized bone defect
      model reveals that the bone regeneration rate is very slow in the CSi-Sr4@CaP-p0
      group, and the bone ingrowth only occurred in the macropores; but in the CSi
      Sr4@CaP-p15 and CSi-Sr4@CaP-p30 groups, the bone ingrowth increased
      significantly. The histological results show that, intriguingly, the hollow core
      after CSi biodissolution favors new bone ingrowth through the porous CaP shell.
      It is reasonable to consider that this new idea could provide insights toward
      designing biphasic composite scaffolds with precisely tuned, time-dependent
      spatiotemporally evolving porous microstructures that are beneficial for bone
      regeneration and repair in situ.

PMID- 30215297
TI  - Patients with Oncocytic Variant Papillary Thyroid Carcinoma Have a Similar
      Prognosis to Matched Classical Papillary Thyroid Carcinoma Controls.
AB  - BACKGROUND: Previous studies have suggested that oncocytic variant papillary
      thyroid carcinoma (PTC) may be more aggressive, with higher rates of recurrent
      disease. The aim of this study was to evaluate characteristics and outcomes of
      patients with oncocytic variant PTC compared to classical PTC. METHODS: Patients
      with oncocytic variant PTC were retrospectively identified from 519 patients who
      underwent thyroidectomy for PTC between January 2009 and August 2015. Data
      collected included patient demographics, laboratory and pathology findings,
      imaging studies, treatment, and follow-up. Patients were matched 1:1 by age, sex,
      and TNM stage with patients who underwent total thyroidectomy for classical PTC
      during the same time period. RESULTS: The cohort included 21 patients, of whom 18
      (86%) were female, with a median age of 53 years (range 23-68 years). All
      patients underwent total thyroidectomy, and 17 (81%) had a central compartment
      neck dissection (8 [38%] prophylactic). The median tumor size was 2.0 cm (range
      0.9-6.5 cm), and four (19%) patients had extrathyroidal extension. There was no
      significant difference in histopathologic characteristics, including
      extrathyroidal extension and lymphovascular invasion, between the two groups
      except for an increased incidence of thyroiditis in oncocytic variant PTC (90.5%
      vs. 57%; p = 0.01). In oncocytic variant PTC patients who underwent central
      compartment neck dissection, malignant lymph nodes were found in 12 (57%)
      patients compared to 13 (62%) classical (p = 0.75). Lateral neck dissection was
      performed in 5 (24%) oncocytic variant and classical PTC patients, with
      metastatic lymphadenopathy found in four (a median of four malignant lymph nodes;
      range 1-6) and five (a median of 2.5 malignant lymph nodes; range 1-9),
      respectively. Radioactive iodine was administered to 18 (86%) oncocytic variant
      PTC and 18 (86%) classical PTC patients. At a median follow-up of 51 months
      (interquartile range 38-61), one oncocytic variant PTC patient had recurrent
      disease and underwent reoperation at 24 months. In classical PTC patients with a
      median follow-up time of 77 months (range 56-87 months), two (9.5%) patients had
      detectable thyroglobulin levels indicating early recurrence, but neither has
      undergone reoperation. CONCLUSIONS: Oncocytic variant PTC was present in 5% of
      PTC patients. Most (95%) patients remain disease-free at four years, similar to
      classical PTC outcomes, suggesting that oncocytic variant may not represent a
      more aggressive variant.

PMID- 30215298
TI  - Aloe-Emodin Ameliorates Renal Fibrosis Via Inhibiting PI3K/Akt/mTOR Signaling
      Pathway In Vivo and In Vitro.
AB  - Fibrosis is the major pathological feature of chronic kidney disease (CKD). Aloe
      emodin (AE), one of the main active compounds in Rhubarb, is widely used for
      renal protection. However, mechanisms implied in the modulation of kidney
      fibrosis after AE treatment for CKD remain elusive. Here, we explored the
      protective effects of AE for renal fibrosis and the involved mechanisms in vivo
      and in vitro. The renal fibrosis mice model was established by unilateral
      ureteral obstruction (UUO). We found that AE administration significantly
      ameliorated UUO-induced impairment of kidney, evidenced by improved
      histopathological abnormalities, body weight, and abnormal renal function in mice
      model. Immunohistochemical staining showed that TGF-beta1 and Fibronectin
      expressions were significantly decreased in UUO mice compared with sham group.
      Meanwhile, we found that AE suppressed the activation of the PI3K/Akt/mTOR
      pathway induced by TGF-beta1 in vivo. AE improved cell survival and decreased the
      level of fibrosis-related proteins under TGF-beta1-induced fibrosis in HK-2 cells
      as well as in vitro. Furthermore, both wortmannin, an inhibitor of PI3K, and
      short-hairpin RNAs of PI3K knockdown abrogated TGF-beta1-induced phosphorylation
      of Akt and mTOR, and decreased the suppression of fibrosis. These findings
      indicated that AE alleviated fibrosis by inhibiting PI3K/Akt/mTOR pathway in vivo
      and in vitro, which may provide a potential therapeutic option for CKD.

PMID- 30215299
TI  - How registered nurses determine their scope of practice: a cross-sectional study.
AB  - In respect of professional nursing, the term scope of practice is regularly used,
      yet is often poorly defined both in Australia and internationally. This study
      explores the determinants of scope of practice from a national sample of
      Australian registered nurses using an online survey (Scope-QAu). This paper
      reports on two parts of a large cross-sectional survey wherein 1231 registered
      nurses in Australia provided data on how they determined their scope of practice.
      Scope of practice in the Australian nursing context is influenced by a range of
      professional publications, guidelines and standards, as well as professional
      peers and one's own judgement. Findings reveal that few demographic
      characteristics predicted the way nurses determined their own scope of practice.
      Nurses commonly relied upon three professional publications, peers and line
      managers, to establish their individual scope of practice. Impact statement:
      Registered nurses do not rely solely on professional guidelines or regulatory
      frameworks when determining their scope of practice.

PMID- 30215301
TI  - Does occlusal splint affect posture? A randomized controlled trial.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of an occlusal splint
      on body posture of intra-articular temporomandibular joint (TMJ) disorders
      patients. METHODS: The study was performed on 45 women affected by TMJ disorders
      divided into an occlusal splint group and a control group. Rasterstereographic
      recordings were performed at baseline and after 1, 3, and 6 months, in order to
      analyze the following postural parameters: trunk inclination, cervical and lumbar
      arrows, kyphotic and lordotic angles, trunk imbalance, pelvic tilt and torsion.
      RESULTS: Regarding the postural parameters in the intragroup analysis, no
      significant differences were detected. The analysis between the two groups
      revealed significant differences concerning the cervical arrow, the kyphotic and
      lordotic angles. DISCUSSION: Even if some differences were found between the
      control and the occlusal splint group, the low range of statistical significance
      made these results not significant from a clinical point of view.

PMID- 30215302
TI  - Suicide Bereavement and Differences in Religiosity.
AB  - BACKGROUND: The trauma from experiencing a loved one's suicide is often seen as
      an instigator of change in a person's religious life. AIMS: We sought to examine
      whether suicide-bereaved adults were any differently disposed to religious
      participation and observances compared with the nonbereaved and whether
      religiously involved bereaved had any better mental health compared with
      religiously disaffiliated bereaved. METHOD: The 2016 General Social Survey (GSS)
      presented 11 new questions identifying suicide bereavement status. We examined
      how the bereaved (n = 516) compared with the nonbereaved (n = 916) in terms of
      their religious beliefs and participation. We also investigated whether suicide
      bereaved religiously committed adherents, who prayed at least weekly (n = 372),
      showed any better mental health compared with bereaved who were religiously
      disaffiliated (n = 102). RESULTS: Initially, results showed the bereaved more
      inclined to pray and to believe in an afterlife compared with the nonbereaved.
      However, after sex differences were controlled for, most of the remaining
      differences between these contrasted groups faded. LIMITATIONS: Caution is
      advised regarding generalizations from these data to all subgroups of suicide
      bereaved due to the modest number of respondents in many subpopulations. The GSS
      does not include potentially important grief-related indices, and importantly,
      most of the current sample were friends of the deceased and not first-degree
      relatives. CONCLUSION: We discuss the implications of these findings and the need
      for further research on the interconnections between religiosity and suicide
      bereavement.

PMID- 30215303
TI  - Over-the-Counter Drugs and Other Substances Used in Attempted Suicide Presented
      to Emergency Departments in Montreal, Canada.
AB  - BACKGROUND: Over-the-counter (OTC) analgesics are frequently used in suicide
      attempts. Accessibility, toxicity, and unsupervised acquisition of large amounts
      may be facilitators. AIMS: To identify patient characteristics associated with
      OTC drug use as a suicide attempt method among adults. METHOD: A cross-sectional
      study was conducted using chart review of all individuals who presented to the
      emergency department (ED) of two adult general hospitals following a suicide
      attempt during 2009-2010 in Montreal, Canada. RESULTS: Among the 369 suicide
      attempters identified, 181 used overdosing, 47% of whom used OTC drugs. In
      logistic regression, women and those with medical comorbidity were more likely to
      use overdosing, while those with substance use disorders were less likely to do
      so. Among those who overdosed, women were more likely to use OTC drugs, while
      those who were Caucasian, had children, comorbidities, diagnoses with substance
      use disorders, and made attempts in the Fall were less likely to do so.
      Substances most frequently used were: acetaminophen among OTC drugs (30%);
      antidepressants (37%), anxiolytics (30%), opioids (10%), and anticonvulsants (9%)
      among prescription drugs; and cocaine (10%) among recreational drugs.
      LIMITATIONS: Reasons for the suicide method choice were not available.
      CONCLUSION: OTC drugs, in particular acetaminophen, are frequently used in
      suicide attempts. Accessibility to these drugs may be an important contributor.

PMID- 30215304
TI  - Estimating the Magnitude of the Relation Between Bullying, E-Bullying, and
      Suicidal Behaviors Among United States Youth, 2015.
AB  - BACKGROUND: Suicide is the second leading cause of death among US adolescents
      aged 12-19 years. Researchers would benefit from a better understanding of the
      direct effects of bullying and e-bullying on adolescent suicide to inform
      intervention work. AIMS: To explore the direct and indirect effects of bullying
      and e-bullying on adolescent suicide attempts (SAs) and to estimate the magnitude
      of these effects controlling for significant covariates. METHOD: This study uses
      data from the 2015 Youth Risk Behavior Surveillance Survey (YRBS), a nationally
      representative sample of US high school youth. We quantified the association
      between bullying and the likelihood of SA, after adjusting for covariates (i.e.,
      sexual orientation, obesity, sleep, etc.) identified with the PC algorithm.
      RESULTS: Bullying and e-bullying were significantly associated with SA in
      logistic regression analyses. Bullying had an estimated average causal effect
      (ACE) of 2.46%, while e-bullying had an ACE of 4.16%. LIMITATIONS: Data are cross
      sectional and temporal precedence is not known. CONCLUSION: These findings
      highlight the strong association between bullying, e-bullying, and SA.

PMID- 30215305
TI  - Utilizing Confocal Microscopy to Characterize Human and Mouse Adipose Tissue.
AB  - Significant advances in our understanding of human obesity, endocrinology, and
      metabolism have been made possible by murine comparative models, in which
      anatomically analogous fat depots are utilized; however, current research has
      questioned how truly analogous these depots are. In this study, we assess the
      validity of the analogy from the perspective of cellular architecture. Whole
      tissue mounting, confocal microscopy, and image reconstruction software were used
      to characterize the three-dimensional structure of the inguinal fat pad in mice,
      gluteofemoral fat in humans, and subcutaneous adipose tissue of the human
      abdominal wall. Abdominal and gluteofemoral adipose tissue specimens from 12
      human patients and bilateral inguinal fat pads from 12 mice were stained for
      adipocytes, blood vessels, and a putative marker for adipose-derived multipotent
      progenitor cells, cluster of differentiation 34 (CD34). Samples were whole
      mounted and imaged with laser scanning confocal microscopy. Expectedly, human
      adipocytes were larger and demonstrated greater size heterogeneity. Mouse fat
      displayed significantly higher vascular density compared with human fat when
      normalized to adipocyte count. There was no significant difference in the
      concentration of CD34-positive (CD34+) stromal cells from either species.
      However, the mean distance between CD34+ stromal cells and blood vessels was
      significantly greater in human fat. Finally, mouse inguinal fat contained larger
      numbers of brown adipocytes than did human gluteofemoral or human abdominal fat.
      Overall, the basic architecture of human adipose tissue differs significantly
      from that of mice. Insofar as human gluteofemoral fat differs from human
      abdominal adipose tissue, it was closer to mouse inguinal fat, being its
      comparative developmental analog. These differences likely confer variance in
      functional properties between the two sources and thus must be considered when
      designing murine models of human disease.

PMID- 30215300
TI  - New strategies in immunotherapy for lung cancer: beyond PD-1/PD-L1.
AB  - Immunotherapy has significantly altered the treatment landscape for many cancers,
      including non-small cell lung cancer (NSCLC). Currently approved immuno-oncology
      agents for lung cancer are aimed at the reversal of immune checkpoints,
      programmed death protein-1 (PD-1) and programmed death ligand-1 (PD-L1). Although
      responses to checkpoint inhibitors are encouraging, and in some cases durable,
      these successes are not universal among all treated patients. In order to
      optimize our treatment approach utilizing immunotherapy, we must better
      understand the interaction between cancer and the immune system and evasion
      mechanisms. In this review, we will provide an overview of the immune system and
      cancer, and review novel therapies that promote tumor antigen release for immune
      system detection, activate the effector T-cell response, and reverse inhibitory
      antitumor signals.

PMID- 30215306
TI  - Diagnosis: History, Physical Examination, Imaging, and Arthroscopy: Proceedings
      of the International Consensus Meeting on Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle are based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article is to report the consensus statements on "Diagnosis: History, Physical
      Examination, Imaging, and Arthroscopy" developed at the 2017 International
      Consensus Meeting on Cartilage Repair of the Ankle. METHODS: Seventy-five
      international experts in cartilage repair of the ankle representing 25 countries
      and 1 territory were convened and participated in a process based on the Delphi
      method of achieving consensus. Questions and statements were drafted within 11
      working groups focusing on specific topics within cartilage repair of the ankle,
      after which a comprehensive literature review was performed and the available
      evidence for each statement was graded. Discussion and debate occurred in cases
      where statements were not agreed upon in unanimous fashion within the working
      groups. A final vote was then held, and the strength of consensus was
      characterized as follows: consensus: 51 - 74%; strong consensus: 75 - 99%;
      unanimous: 100%. RESULTS: A total of 12 statements on the diagnosis of cartilage
      injuries of the ankle reached consensus during the 2017 International Consensus
      Meeting on Cartilage Repair of the Ankle. Two achieved unanimous support and 10
      reached strong consensus (greater than 75% agreement). All statements reached at
      least 86% agreement. CONCLUSIONS: This international consensus derived from
      leaders in the field will assist clinicians in the diagnosis of cartilage
      injuries of the ankle.

PMID- 30215307
TI  - Debridement, Curettage, and Bone Marrow Stimulation: Proceedings of the
      International Consensus Meeting on Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle are based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article is to report the consensus statements on "Debridement, Curettage and Bone
      Marrow Stimulation" developed at the 2017 International Consensus Meeting on
      Cartilage Repair of the Ankle. METHODS: Seventy-five international experts in
      cartilage repair of the ankle representing 25 countries and 1 territory were
      convened and participated in a process based on the Delphi method of achieving
      consensus. Questions and statements were drafted within 11 working groups
      focusing on specific topics within cartilage repair of the ankle, after which a
      comprehensive literature review was performed and the available evidence for each
      statement was graded. Discussion and debate occurred in cases where statements
      were not agreed upon in unanimous fashion within the working groups. A final vote
      was then held, and the strength of consensus was characterized as follows:
      consensus, 51% to 74%; strong consensus, 75% to 99%; unanimous, 100%. RESULTS: A
      total of 14 statements on debridement, curettage, and bone marrow stimulation
      reached consensus during the 2017 International Consensus Meeting on Cartilage
      Repair of the Ankle. One achieved unanimous support, 12 reached strong consensus
      (greater than 75% agreement), and 1 achieved consensus. All statements reached at
      least 72% agreement. CONCLUSIONS: This international consensus derived from
      leaders in the field will assist clinicians with debridement, curettage and bone
      marrow stimulation as a treatment strategy for osteochondral lesions of the
      talus.

PMID- 30215308
TI  - Osteochondral Allograft: Proceedings of the International Consensus Meeting on
      Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle is based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article is to report the consensus statements on "Osteochondral Allograft"
      developed at the 2017 International Consensus Meeting on Cartilage Repair of the
      Ankle. METHODS: Seventy-five international experts in cartilage repair of the
      ankle representing 25 countries and 1 territory were convened and participated in
      a process based on the Delphi method of achieving consensus. Questions and
      statements were drafted within 11 working groups focusing on specific topics
      within cartilage repair of the ankle, after which a comprehensive literature
      review was performed and the available evidence for each statement was graded.
      Discussion and debate occurred in cases where statements were not agreed upon in
      unanimous fashion within the working groups. A final vote was then held, and the
      strength of consensus was characterized as follows: consensus, 51% to 74%; strong
      consensus, 75% to 99%; and unanimous, 100%. RESULTS: A total of 15 statements on
      osteochondral allograft reached consensus during the 2017 International Consensus
      Meeting on Cartilage Repair of the Ankle. One achieved unanimous support and 14
      reached strong consensus (greater than 75% agreement). All statements reached at
      least 85% agreement. CONCLUSIONS: This international consensus derived from
      leaders in the field will assist clinicians with osteochondral allograft as a
      treatment strategy for osteochondral lesions of the talus.

PMID- 30215309
TI  - Osteochondral Autograft: Proceedings of the International Consensus Meeting on
      Cartilage Repair of the Ankle.
AB  - BACKGROUND: Treatment guidelines for cartilage lesions of the talus have been
      based on both low quality and low levels of evidence. Therefore, an international
      consensus group of experts was convened to collaboratively advance toward
      consensus opinions on key topics regarding cartilage lesions of the talus. The
      purpose of this consensus article is to explain the process and delineate the
      consensus statements derived from this consensus meeting on the use of
      "osteochondral autograft" for osteochondral lesions of the talus. METHODS:
      Seventy-five international experts in cartilage repair of the ankle representing
      25 countries and 1 territory were convened and participated in a process based on
      the Delphi method of achieving consensus. Questions and statements were drafted
      within 11 working groups focusing on specific topics within cartilage repair of
      the ankle, after which a comprehensive literature review was performed and the
      available evidence for each statement was graded. Discussion and debate occurred
      in cases where statements were not agreed upon in unanimous fashion within the
      working groups. A final vote was then held, and the strength of consensus was
      characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%;
      and unanimous, 100%. RESULTS: A total of 14 statements on osteochondral autograft
      reached consensus during the 2017 International Consensus Meeting on Cartilage
      Repair of the Ankle. Two achieved unanimous support, 11 reached strong consensus
      (greater than 75% agreement), and 1 achieved consensus. All statements reached at
      least 67% agreement. CONCLUSIONS: This international consensus derived from
      leaders in the field will assist clinicians with osteochondral autograft as a
      treatment strategy for osteochondral lesions of the talus.

PMID- 30215310
TI  - Fixation Techniques: Proceedings of the International Consensus Meeting on
      Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle is based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article is to report the consensus statements on "Fixation Techniques" developed
      at the 2017 International Consensus Meeting on Cartilage Repair of the Ankle.
      METHODS: Seventy-five international experts in cartilage repair of the ankle
      representing 25 countries and 1 territory were convened and participated in a
      process based on the Delphi method of achieving consensus. Questions and
      statements were drafted within 11 working groups focusing on specific topics
      within cartilage repair of the ankle, after which a comprehensive literature
      review was performed and the available evidence for each statement was graded.
      Discussion and debate occurred in cases where statements were not agreed upon in
      unanimous fashion within the working groups. A final vote was then held, and the
      strength of consensus was characterized as follows: consensus, 51% to 74%; strong
      consensus, 75% to 99%; and unanimous, 100%. RESULTS: A total of 15 statements on
      fixation techniques reached consensus during the 2017 International Consensus
      Meeting on Cartilage Repair of the Ankle. All 15 statements achieved strong
      consensus, with at least 82% agreement. CONCLUSIONS: This international consensus
      derived from leaders in the field will assist clinicians with using fixation
      techniques in the treatment of osteochondral lesions of the talus.

PMID- 30215311
TI  - Subchondral Pathology: Proceedings of the International Consensus Meeting on
      Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle are based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article is to report the consensus statements on "Subchondral Pathology"
      developed at the 2017 International Consensus Meeting on Cartilage Repair of the
      Ankle. METHODS: Seventy-five international experts in cartilage repair of the
      ankle representing 25 countries and 1 territory were convened and participated in
      a process based on the Delphi method of achieving consensus. Questions and
      statements were drafted within 11 working groups focusing on specific topics
      within cartilage repair of the ankle, after which a comprehensive literature
      review was performed and the available evidence for each statement was graded.
      Discussion and debate occurred in cases where statements were not agreed upon in
      unanimous fashion within the working groups. A final vote was then held, and the
      strength of consensus was characterized as follows: consensus, 51% to 74%; strong
      consensus, 75% to 99%; unanimous, 100%. RESULTS: A total of 9 statements on
      subchondral pathology reached consensus during the 2017 International Consensus
      Meeting on Cartilage Repair of the Ankle. No statements achieved unanimous
      support, but all statements reached strong consensus (greater than 75%
      agreement). All statements reached at least 81% agreement. CONCLUSIONS: This
      international consensus statements regarding subchondral pathology of the talus
      derived from leaders in the field will assist clinicians in the assessment and
      management of this difficult pathology.

PMID- 30215312
TI  - Scaffold-Based Therapies: Proceedings of the International Consensus Meeting on
      Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle are based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article is to report the consensus statements on "Scaffold-Based Therapies"
      developed at the 2017 International Consensus Meeting on Cartilage Repair of the
      Ankle. METHODS: Seventy-five international experts in cartilage repair of the
      ankle representing 25 countries and 1 territory were convened and participated in
      a process based on the Delphi method of achieving consensus. Questions and
      statements were drafted within 11 working groups focusing on specific topics
      within cartilage repair of the ankle, after which a comprehensive literature
      review was performed and the available evidence for each statement was graded.
      Discussion and debate occurred in cases where statements were not agreed upon in
      unanimous fashion within the working groups. A final vote was then held, and the
      strength of consensus was characterized as follows: consensus, 51% to 74%; strong
      consensus, 75% to 99%; unanimous, 100%. RESULTS: A total of 9 statements on
      scaffold-based therapies reached consensus during the 2017 International
      Consensus Meeting on Cartilage Repair of the Ankle. One achieved unanimous
      support, 8 reached strong consensus (greater than 75% agreement), and 1 was
      removed because of redundancy in the information provided. All statements reached
      at least 80% agreement. CONCLUSIONS: This international consensus derived from
      leaders in the field will assist clinicians with applying scaffold-based
      therapies as a treatment strategy for osteochondral lesions of the talus. LEVEL
      OF EVIDENCE: Level V, expert opinion.

PMID- 30215313
TI  - Rehabilitation and Return to Sports: Proceedings of the International Consensus
      Meeting on Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle are based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article is to report the consensus statements on Rehabilitation and Return to
      Sports developed at the 2017 International Consensus Meeting on Cartilage Repair
      of the Ankle. METHODS: Seventy-five international experts in cartilage repair of
      the ankle representing 25 countries and 1 territory were convened and
      participated in a process based on the Delphi method of achieving consensus.
      Questions and statements were drafted within 11 working groups focusing on
      specific topics within cartilage repair of the ankle, after which a comprehensive
      literature review was performed and the available evidence for each statement was
      graded. Discussion and debate occurred in cases where statements were not agreed
      upon in unanimous fashion within the working groups. A final vote was then held,
      and the strength of consensus was characterized as follows: consensus, 51% to
      74%; strong consensus, 75% to 99%; unanimous, 100%. RESULTS: A total of 9
      statements on rehabilitation and return to sports reached consensus during the
      2017 International Consensus Meeting on Cartilage Repair of the Ankle. All 9
      statements reached strong consensus, with at least 86% agreement. CONCLUSIONS:
      The rehabilitation process for an ankle cartilage injury requires a
      multidisciplinary and comprehensive approach. This international consensus
      derived from leaders in the field will assist clinicians with rehabilitation and
      return to sports after treatment of a cartilage injury of the ankle.

PMID- 30215314
TI  - Conservative Management and Biological Treatment Strategies: Proceedings of the
      International Consensus Meeting on Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle are based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article is to report the consensus statements on "Conservative Management and
      Biological Treatment Strategies" developed at the 2017 International Consensus
      Meeting on Cartilage Repair of the Ankle. METHODS: Seventy-five international
      experts in cartilage repair of the ankle representing 25 countries and 1
      territory were convened and participated in a process based on the Delphi method
      of achieving consensus. Questions and statements were drafted within 11 working
      groups focusing on specific topics within cartilage repair of the ankle, after
      which a comprehensive literature review was performed and the available evidence
      for each statement was graded. Discussion and debate occurred in cases where
      statements were not agreed upon in unanimous fashion within the working groups. A
      final vote was then held, and the strength of consensus was characterized as
      follows: consensus, 51% to 74%; strong consensus, 75% to 99%; unanimous, 100%.
      RESULTS: A total of 12 statements on Conservative Management and Biological
      Treatment Strategies reached consensus during the 2017 International Consensus
      Meeting on Cartilage Repair of the Ankle. Ten statements reached strong consensus
      (greater than 75% agreement), and 2 achieved consensus. CONCLUSIONS: This
      international consensus derived from leaders in the field will assist clinicians
      with conservative management and biological treatment strategies for
      osteochondral lesions of the talus.

PMID- 30215318
TI  - Letter about a Published Paper: Can surgical guidelines minimize complications
      after Maia(r) trapeziometacarpal joint arthroplasty with unconstrained cups?

PMID- 30215317
TI  - Generation of Footprint-Free Canine Induced Pluripotent Stem Cells Using Auto
      Erasable Sendai Virus Vector.
AB  - Canine induced pluripotent stem cells (ciPSCs) can be used in regenerative
      medicine. However, there are no reports on the generation of genome integration
      free and completely exogenous gene-silenced (footprint free) ciPSCs that are
      tolerant to enzymatic single-cell passage. In this study, we reprogrammed canine
      embryonic fibroblasts using the auto-erasable replication-defective and
      persistent Sendai virus vector, SeVdp(KOSM)302L, and generated two ciPSC lines.
      The ciPSCs were positive for pluripotent markers, including alkaline phosphatase
      activity as well as OCT3/4, SOX2, and NANOG transcripts, and NANOG, stage
      specific embryonic antigen-1, and partial TRA-1-60 protein expression, even after
      SeVdp(KOSM)302L removal. The ciPSCs were induced to differentiate into all the
      three germ layers as embryoid bodies in vitro and as teratomas in vivo.
      Furthermore, SeVdp(KOSM)302L-free ciPSCs maintained a normal karyotype even after
      repeated enzymatic single-cell passaging. Therefore, to our knowledge, for the
      first time, we demonstrated the generation of footprint-free and high-quality
      ciPSCs that can be passaged at the single-cell stage using enzymatic methods. Our
      method for generation of ciPSCs is a good step toward the development of clinical
      application of ciPSCs.

PMID- 30215319
TI  - Reply.

PMID- 30215315
TI  - Revision and Salvage Management: Proceedings of the International Consensus
      Meeting on Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle are based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article was to report on the consensus statements on "Revision and Salvage
      Management" developed at the 2017 International Consensus Meeting on Cartilage
      Repair of the Ankle. METHODS: Seventy-five international experts in cartilage
      repair of the ankle representing 25 countries and 1 territory were convened and
      participated in a process based on the Delphi method of achieving consensus.
      Questions and statements were drafted within 11 working groups focusing on
      specific topics within cartilage repair of the ankle, after which a comprehensive
      literature review was performed and the available evidence for each statement was
      graded. Discussion and debate occurred in cases where statements were not agreed
      on in unanimous fashion within the working groups. A final vote was then held,
      and the strength of consensus was characterized as follows: consensus, 51% to
      74%; strong consensus, 75% to 99%; unanimous, 100%. RESULTS: A total of 8
      statements on revision and salvage management reached consensus during the 2017
      International Consensus Meeting on Cartilage Repair of the Ankle. One achieved
      unanimous support and 7 reached strong consensus (greater than 75% agreement).
      All statements reached at least 85% agreement. CONCLUSIONS: This international
      consensus derived from leaders in the field will assist clinicians with revision
      and salvage management in the cartilage repair of the ankle.

PMID- 30215316
TI  - Post-treatment Follow-up, Imaging, and Outcome Scores: Proceedings of the
      International Consensus Meeting on Cartilage Repair of the Ankle.
AB  - BACKGROUND: The evidence supporting best practice guidelines in the field of
      cartilage repair of the ankle are based on both low quality and low levels of
      evidence. Therefore, an international consensus group of experts was convened to
      collaboratively advance toward consensus opinions based on the best available
      evidence on key topics within cartilage repair of the ankle. The purpose of this
      article is to report the consensus statements on Post-treatment Follow-up,
      Imaging and Outcome Scores developed at the 2017 International Consensus Meeting
      on Cartilage Repair of the Ankle. METHODS: Seventy-five international experts in
      cartilage repair of the ankle representing 25 countries and 1 territory were
      convened and participated in a process based on the Delphi method of achieving
      consensus. Questions and statements were drafted within 11 working groups
      focusing on specific topics within cartilage repair of the ankle, after which a
      comprehensive literature review was performed and the available evidence for each
      statement was graded. Discussion and debate occurred in cases where statements
      were not agreed on in unanimous fashion within the working groups. A final vote
      was then held, and the strength of consensus was characterized as follows:
      consensus, 51% to 74%; strong consensus, 75% to 99%; unanimous, 100%. RESULTS: A
      total of 12 statements on Post-treatment Follow-up, Imaging, and Outcome Scores
      reached consensus during the 2017 International Consensus Meeting on Cartilage
      Repair of the Ankle. All 12 statements reached strong consensus (greater than 75%
      agreement). CONCLUSIONS: This international consensus derived from leaders in the
      field will assist clinicians with post-treatment follow-up, imaging, and outcome
      scores after management of a cartilage injury of the ankle in the general
      population. Moreover, healing, rehabilitation, and final outcomes can be
      optimized for the individual patient.

PMID- 30215320
TI  - Lasting power of graphic records of clinical findings and explicit drawings of
      surgical procedures.

PMID- 30215321
TI  - Randomized controlled trials in surgery of the hand: where we are.

PMID- 30215322
TI  - Hand Surgery in Ireland.

PMID- 30215323
TI  - Letter about a Published Paper: The hand injury caused by cutting avocado in 18
      patients.

PMID- 30215324
TI  - In this issue of Adipocyte.

PMID- 30215326
TI  - Cardiovascular and Hematological Medicine in 2018 - Advances and Insights.

PMID- 30215327
TI  - Pegylated Naloxone in the Treatment of Persistent Opioid-Induced Constipation in
      Patients with Hematological Malignancies.

PMID- 30215328
TI  - Novel Chemotherapeutic Agents - The Contribution of Scorpionates.
AB  - The development of safe and effective chemotherapeutic agents is one of the
      uppermost priorities and challenges of medicinal chemistry and new transition
      metal complexes are being continuously designed and tested as anticancer agents.
      Scorpionate ligands have played a great role in coordination chemistry, since
      their discovery by Trofimenko in the late 1960s, with significant contributions
      in the fields of catalysis and bioinorganic chemistry. Scorpionate metal
      complexes have also shown interesting anticancer properties, and herein, the most
      recent (last decade) and relevant scorpionate complexes reported for application
      in medicinal chemistry as chemotherapeutic agents are reviewed. The current
      progress on the anticancer properties of transition metal complexes bearing homo-
      or hetero- scorpionate ligands, derived from bis- or tris-(pyrazol-1-yl)-borate
      or -methane moieties is highlighted.

PMID- 30215325
TI  - Accelerate Healing of Severe Burn Wounds by Mouse Bone Marrow Mesenchymal Stem
      Cell-Seeded Biodegradable Hydrogel Scaffold Synthesized from Arginine-Based
      Poly(ester amide) and Chitosan.
AB  - Severe burns are some of the most challenging problems in clinics and still lack
      ideal modalities. Mesenchymal stem cells (MSCs) incorporated with biomaterial
      coverage of burn wounds may offer a viable solution. In this report, we seeded
      MSCs to a biodegradable hybrid hydrogel, namely ACgel, that was synthesized from
      unsaturated arginine-based poly(ester amide) (UArg-PEA) and chitosan derivative.
      MSC adhered to ACgels. ACgels maintained a high viability of MSCs in culture for
      6 days. MSC seeded to ACgels presented well in third-degree burn wounds of mice
      at 8 days postburn (dpb) after the necrotic full-thickness skin of burn wounds
      was debrided and filled and covered by MSC-carrying ACgels. MSC-seeded ACgels
      promoted the closure, reepithelialization, granulation tissue formation, and
      vascularization of the burn wounds. ACgels alone can also promote vascularization
      but less effectively compared with MSC-seeded ACgels. The actions of MSC-seeded
      ACgels or ACgels alone involve the induction of reparative, anti-inflammatory
      interleukin-10, and M2-like macrophages, as well as the reduction of inflammatory
      cytokine TNFalpha and M1-like macrophages at the late inflammatory phase of burn
      wound healing, which provided the mechanistic insights associated with
      inflammation and macrophages in burn wounds. For the studied regimens of these
      treatments, no toxicity was identified to MSCs or mice. Our results indicate that
      MSC-seeded ACgels have potential use as a novel adjuvant therapy for severe burns
      to complement commonly used skin grafting and, thus, minimize the downsides of
      grafting.

PMID- 30215329
TI  - Surface modification by nanobiomaterials for vascular tissue engineering
      applications.
AB  - Treatment of cardiovascular disease has achieved great success using artificial
      implants, particularly synthetic-polymer made grafts. However, thrombus formation
      and restenosis are the current clinical problems need to be conquered. New
      biomaterials, modifying the surface of synthetic vascular grafts, have been
      created to improve long-term patency for the better hemocompatibility." The
      vascular biomaterials can be fabricated from synthetic or natural polymers for
      vascular tissue engineering. Stem cells can be seeded by different techniques
      into tissue-engineered vascular grafts in vitro and implanted in vivo to repair
      the vascular tissues. To overcome the thrombogenesis and promote the
      "endothelialization" effect, vascular biomaterials employing nanotopograpjy are
      more bio-mimic to the native tissue made and have been engineered by various
      approaches such as prepared as a simple surface coating on the vascular
      biomaterials. "It has now become an important and interesting field to find novel
      approaches to better endothelization of vascular biomaterials. In this article,
      we focus to review the techniques with better potential improving endothelization
      and summarize for vascular biomaterial application." This review article will
      enable the development of biomaterials with a high degree of originality,
      innovative research on novel techniques for surface fabrication for vascular
      biomaterials application".

PMID- 30215330
TI  - Implantable medical devices and tissue engineering: An overview of manufacturing
      processes and the use of polymeric matrices for manufacturing and coating their
      surfaces.
AB  - Medical devices are important diagnosis and therapy tools for several diseases
      which include a wide range of products. Technological advances in this area have
      been proposed to reduce adverse complication incidences. New technologies and
      manufacturing processes, as well as development of new materials or medical
      devices with modified surface and the use of biodegradable polymeric devices such
      as substrate for cell culture in the field of tissue engineering have attracted
      considerable attention in recent years by the scientific community intended to
      produce medical devices with superior properties and morphology. This review
      article focused on implantable devices, addresses the major advances in the
      biomedical field related to the devices manufacture processes such as 3D printing
      and hot melting extrusion, and the use of polymer matrices composed of
      copolymers, blends, nanocomposites or grafted with antiproliferative drugs for
      manufacturing and/or coating the devices surface.

PMID- 30215331
TI  - Novel diagnostic biomarkers of prostate cancer: an update.
AB  - OBJECTIVE: In recent years, several biomarkers alternative to standard prostate
      specific antigen (PSA) for prostate cancer (PCa) diagnosis have become available.
      The aim of this systematic review is to assess the current knowledge about
      alternative serum and urinary biomarkers for the diagnosis of PCa. Material and
      Methods A research was conducted in Medline, restricted to English language
      articles published between December 2014 and June 2018 with the aim to update
      previously published series on PCa biomarkers. The preferred reporting items for
      systematic reviews and meta-analyses (PRISMA) criteria were used for selecting
      studies with the lowest risk of bias. Results Emerging role and actual
      controversies on serum and urine alternative biomarkers to standard PSA for PCa
      diagnosis, staging and prognosis assessment, such as prostate health index (PHI),
      PCA3, ConfirmMDx, Aberrant PSA glycosylation, MiPS, miRNAs are critically
      presented in the current review. Conclusions Although the use of several
      biomarkers have been recommended or questioned by different international
      guidelines, larger prospective randomized studies are still necessary to validate
      their efficacy in PCa detection, discrimination, prognosis and treatment
      effectiveness. To date, only PHI and 4Kscore have showed a clinical relevance for
      discriminating more aggressive PCa. Furthermore, a new grading classification
      based on molecular features relevant for PCa risk-stratification and tailoring
      treatment is still needed.

PMID- 30215332
TI  - Simultaneous Electrochemical Evaluation of Ascorbic Acid, Epinephrine and Uric
      Acid at Disposable Pencil Graphite Electrode: Highly Sensitive Determination in
      Pharmaceuticals and Biological Liquids by Differential Pulse Voltammetry.
AB  - AIM AND OBJECTIVE: As is known, AA, EP and UA can also coexist in biological
      fluids. Therefore, the determination of the levels of these compounds in
      biological fluids is extremely important both for the diagnosis and treatment of
      the related diseases. In the presence of many interfering substances in
      biological fluids such as blood and urine samples, it is very important that
      these compounds can be selectively analyzed. MATERIALS AND METHODS: All
      electrochemical experiments were performed using an Autolab PGSTAT 128N
      potentiostat. Before beginning the electrochemical measurements, the PGE was
      activated. The electrochemical pretreatment of PG was exercised by anodically
      +1.40 V for 60 s. Then, measurements were performed with CV (-0.4 V to 1.2 V) and
      DPV (-0.2 V to 0.7 V) for single and simultaneous voltammetric behaviour of AA,
      EP, and UA in the electrochemical method. RESULTS: The anodic peak potentials of
      AA and UA were observed at about +0.32 V and +0.62 V, respectively. On the other
      hand, for EP, while anodic peak potential was observed at about +0.53 V, in the
      reverse scan, cathodic peak potentials were observed at about +0.41 V and +0.007
      V. The reduction peak observed at +0.3 V with the oxidation peak observed at
      +0.53 V are the reversible peaks. In the method developed for the electrochemical
      simultaneous determination of AA, EP and UA using PGE with DPV technique in BR
      buffer solution (pH 4.0), the anodic peak potentials are sufficiently separated
      from each other. CONCLUSION: A voltammetric method was developed for the
      simultaneous determination of AA, EP and UA with PGE for the first time. Here,
      the most important thing is that the simultaneous determination of AA, EP and UA
      was successfully achieved with that targeted voltammetric method which was
      sensitive, low-cost, practical and well-repeated; and that these were proven to
      be selectively applicable in pharmaceutical products and biological liquids.

PMID- 30215333
TI  - DNA repair proteins as therapeutic targets in ovarian cancer.
AB  - Epithelial ovarian cancer is a serious public health problem worldwide with the
      highest mortality rate of all gynecologic cancers. The current standard-of-care
      for the treatment of ovarian cancer is based on chemotherapy based on adjuvant
      cisplatin/carboplatin and taxane regimens that represent the first-line agents
      for patients with advanced disease. The DNA repair activity of cancer cells
      determines the efficacy of anticancer drugs. These features make DNA repair
      mechanisms a promising target for novel cancer treatments. In this context a
      better understanding of the DNA damage response caused by antitumor agents has
      provided the basis for the use of DNA repair inhibitors to improve the
      therapeutic use of DNA-damaging drugs. In this review, we will discuss the
      functions of DNA repair proteins and the advances in targeting DNA repair
      pathways with special emphasis in the inhibition of HRR and BER in ovarian
      cancer. We focused in the actual efforts in the development and clinical use of
      poly (ADP-ribose) polymerase (PARP) inhibitors for the intervention of
      BRCA1/BRCA2-deficient ovarian tumors. The clinical development of PARP inhibitors
      in ovarian cancer patients with germline BRCA1/2 mutations and sporadic high
      grade serous ovarian cancer is ongoing. Some phase II and phase III trials have
      been completed with promising results for ovarian cancer patients.

PMID- 30215334
TI  - Targeting Matrix Metalloproteinases for Diabetic Retinopathy: the way ahead?
AB  - Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes.
      It causes progressive damage to the retina and is the most common cause of vision
      impairment and blindness among diabetic patients. DR develops as a result of
      various changes in the ocular environment. Such changes include accelerated
      mitochondrial dysfunction, apoptosis, reactive oxygen species production, and
      formation of acellular capillaries. Matrix metalloproteinases (MMPs) are one of
      the major culprits in causing DR. Under physiological conditions, MMPs cause
      remodeling of the extracellular matrix in the retina, while under pathological
      conditions, they induce retinal cell apoptosis. This review focuses on the roles
      of various MMPs, primarily MMP-2 and MMP-9 in DR and also their participation in
      oxidative stress, mitochondrial dysfunction, and apoptosis, along with their
      involvement in various signaling pathways. This review also underscores different
      strategies to inhibit MMPs, thus suggesting that MMPs may represent a putative
      therapeutic target in the treatment of DR.

PMID- 30215335
TI  - Fabrication and Characterization of Electrospun Nanofibers for the Modified
      Release of the Chronobiotic Hormone Melatonin.
AB  - OBJECTIVE: Aiming at the modified release of melatonin (MLT), electrospun-MLT
      loaded nanofibers, filled into hard gelatin and DRcapsTM capsules, were used as
      formulants. METHODS: Cellulose acetate, polyvinylpyrrolidinone and
      hydroxypropylmethylcellusose (HPMC 2910) were used for the preparation of the
      fiber matrices through electrospinning. The in vitro modified release profile of
      MLT from the fabricated matrices in gastrointestinal-like fluids was studied. At
      pH 1.2, the formulations CA1, CA2, PV1, HP1, HP2 and the composite formulations
      CAPV1-CAPV5 in hard gelatin capsules exhibited fast MLT release. RESULTS: In
      general, the same trend was observed at pH 6.8, with the exception of CAPV1 and
      CAPV2. These two composite formulations delivered 52.08% and 75.25% MLT,
      respectively at a slower pace (6 h) when encapsulated in DRcapsTM capsules. In
      all other cases, the release of MLT from DRcapsTM capsules filled with the MLT
      loaded nanofibers reached 100% at 6h. CONCLUSION: These findings suggest that the
      MLT-loaded nanofibrous mats developed in this study exhibit a promising profile
      for treating sleep dysfunctions.

PMID- 30215336
TI  - Lignans' potential in pre- and post-onset type 2 diabetes management.
AB  - INTRODUCTION: Type 2 diabetes (T2D) cases continue to rise dramatically despite
      efforts to get people to exercise and eat with a view to health and combatting
      the cluster of 7 issues (elevated waist circumference, hyperglycaemia,
      hypertension, dyslipidemia, pro-thrombotic state, increased oxidation (including
      low density lipoprotein (LDL)) and the pro-inflammatory state associated with pre
      and post-onset T2D. BACKGROUND: There are numerous medications available to deal
      with these seven major issues. However, each medication currently available
      manages a maximum of two cluster members at a time. Consequently, polypharmacy is
      frequently required to manage the cluster of seven. Polypharmacy brings with it
      high financial costs for numerous medications, the risk of poor compliance
      (particularly so in older patients), side effects and drug interactions. Thus,
      there is a search for new agents that reduce the high costs and risks of
      polypharmacy while at the same time combatting three or more of the cluster of
      seven. There is very limited evidence to suggest that one or more lignans may
      efficaciously and safely, in the short and long term, manage at least three of
      the cluster of seven, pre- and post-T2D onset, thus reducing polypharmacy.
      However, multi-centre, large, clinical trials are required before any definitive
      conclusions about these lignans can be reached regarding its safe and efficacious
      polypharmacy reduction potential, both long and short term, in pre- and post
      onset T2D management. CONCLUSION: It is concluded that some lignans appear to
      have the potential to manage at least three members of the cluster of seven in
      pre- or post-T2D onset and hence reduce polypharmacy but much more investigation
      is required to confirm if such is the case. At the moment there is not enough
      evidence that any of the lignans will, in the long or short term, safely and
      efficaciously manage the cluster of seven via polypharmacy reduction.

PMID- 30215337
TI  - Comparing Allergist And Cardiologist Considerations For The Optimal Management Of
      Thienopyridines Hypersensitivity.
AB  - The thienopyridine family includes ticlopidine, clopidogrel and prasugrel which
      are antiplatelet drugs largely used, mainly associated to aspirin, for treatment
      of acute coronary syndromes and after percutaneous coronary interventions, to
      avoid thrombosis. In some patients, thienpyridines may cause hypersensitivity
      reactions which jeopardize the optimal therapeutic and preventive approach to
      vascular diseases. The management of thienopyridine hypersensitivity is best done
      as an interdisciplinary collaboration between the allergist and cardiologist. For
      the cardiologist, the important issues are the necessity of continuing therapy,
      the desired duration of therapy based on the clinical indication of the
      individual patient and appropiateness of using one of the alternative P2Y12
      inhibitors. For the allergist, the important issues are weighing the risk and
      benefits of the various therapeutic options: treating "through" desensitization
      or switching to an alternative agent. Working togetther, a cardio-allergy team of
      specialists may offer the best approach to clinical decision making for the
      indivual paient.

PMID- 30215338
TI  - Hepatic Flavin-containing Monooxygenase and Aldehyde Oxidase Activities in Male
      Domestic Pigs at Different Ages.
AB  - BACKGROUND: Age has significant impact on activities of hepatic metabolizing
      enzymes in humans and animals. Flavin-containing monooxygenase (FMO) and aldehyde
      oxidase are two important hepatic enzymes. Understanding of impact of age on
      these two enzymes is still limited. This work was to investigate growth impact on
      hepatic FMO and AO activities in domestic male pigs. METHODS: Porcine liver
      microsomes and cytosol were prepared from the livers of male domestic pigs at
      ages of 1 day, 2, 5, 10 and 20 weeks. FMO activity was assessed using N-oxidation
      of benzydamine in porcine liver microsomes and AO activity was evaluated using
      oxidation of O6-benzylguanine in porcine liver cytosol. RESULTS: Porcine hepatic
      FMO activity was substantial at the age of 1 day, rapidly increased in 2 weeks,
      and remained high afterwards. Porcine hepatic AO activity was minimal at the age
      of 1 day and gradually increased to the maximum in 5 weeks and remained
      relatively constant to the age of 20 weeks. Porcine hepatic FMO activity is
      higher than other species, including human. Age-dependent FMO developmental
      pattern in porcine liver is different from porcine hepatic CYP450 and human
      hepatic FMO. Porcine hepatic AO activity is much lower than human although their
      developmental patterns are similar. CONCLUSION: Age impact on hepatic activities
      of both FMO and AO is obvious in domestic male pigs although age patterns of both
      enzymes are different.

PMID- 30215339
TI  - Determination of gamma camera's calibration factors for quantitation of
      diagnostic radionuclides in simultaneous scattering and attenuation correction.
AB  - OBJECTIVE: The characterization of cancerous tissue and bone metastasis can be
      distinguished by the accurate assessment of accumulated uptake and activity from
      different radioisotopes. The various parameters and phenomena such as calibration
      factor, Compton scattering, attenuation and penetration are influenced intrinsic
      this quantity, and the qualification of images as well. METHODS: The camera
      calibration factor (CF) translates reconstructed count map into absolute activity
      map, is determined by both planar and tomographic scans using different phantom
      geometries. In this study, the CF for radionuclides of Tc-99m and Sm-153 in soft
      tissue and bone was simulated by Monte Carlo method, and experimental results
      were obtained in equivalent tissue and bone phantoms. It may be employed to
      correct simultaneously the scattering and attenuation rays interacted to the
      camera, leading to corrected counts. Also, the target depth (d) may be estimated
      by combination of scattering and photoelectric functions, which we have published
      before. RESULTS: The calibrated equations for soft tissue phantom for the
      radionuclides were obtained by RTc = -10d+ 300 and RSm = -8d + 100, and the
      relative errors between the simulated and experimental results were 4.5% and
      3.1%, respectively. The equations for bone phantom were RTc = -30d + 300 and RSm
      = -10d + 100, and the relative errors were 5.4% and 5.6%. The R and d are in
      terms of cpm/mCi and cm. Besides, the collimators' impact was evaluated on the
      camera response, and the relevant equations were obtained by Monte Carlo method.
      The calibrated equations as a function of various radiation angles on the central
      of camera's cells without using collimator indicated that both sources have the
      same quadratic coefficient by -2E-08 and same vertical width from the origin by
      8E-05. CONCLUSION: The presented procedure may help to determine the absorbed
      dose in target and likewise to optimize treatment planning.

PMID- 30215340
TI  - Review: Domestic herbivores and food security: current contribution, trends and
      challenges for a sustainable development.
AB  - Herbivores are found in a variety of ecosystems all over the world. Permanent
      pastures and meadows cover about 25% of global land. We currently count one
      domesticated herbivore for two people in the world and the number is growing.
      Production systems and products are highly diverse. This high diversity is the
      result of thousands of years of natural selection and human-controlled breeding,
      as well as migration and trade. Because of the high diversity of domestic
      herbivore genetic resources, herders have been able to live in regions where no
      alternative for income generation exists. Meat and milk from domestic herbivores
      provide 16% and 8% of the global protein and kilocalorie consumption,
      respectively. They also provide a variety of essential micronutrients but can
      contribute to overweight and obesity when consumed in excess. Domestic herbivores
      also make significant contribution to food security through the production of
      manure, draught power and transport and the generation of income at household and
      national level. They have a key role to play in women's empowerment and gender
      equality, both in rural and urban areas.Demand for meat and milk is increasing
      because of population growth, rising incomes and urbanisation. This trend is
      expected to continue, especially in Latin America, South Asia and China. The
      sustainable development of domestic herbivore production needs to address the
      feed/food and the efficiency of herbivores in turning forages into protein. It
      also needs to address the contribution of herbivores to greenhouse gas emissions,
      especially of ruminants through enteric fermentation, and their mitigation
      potential, including through carbon sequestration. Animal genetic resources have
      a key role to play in mitigating and adapting to climate change. The role of
      ruminants in the circular bioeconomy needs to be enhanced, promoting the use of
      by-products and waste as livestock feed and the recycling of manure for energy
      and nutrients. Finally, the role of domestic herbivores in providing secure
      livelihoods and economic opportunities for millions of smallholder farmers and
      pastoralists needs to be enhanced. The sustainable development of the sector
      therefore requires adequate policies, and there are already a variety of
      mechanisms available, including regulations, cross-compliance systems, payments
      for environmental services and research and development. Priority areas for
      policy makers should be aligned with the global framework of the Sustainable
      Development Goals and include: (i) food security and nutrition, (ii) economic
      development and livelihoods, (iii) animal and human health and finally, (iv)
      environment, climate and natural resources.

PMID- 30215341
TI  - Seafood consumption patterns, their nutritional benefits and associated
      sociodemographic and lifestyle factors among First Nations in British Columbia,
      Canada.
AB  - OBJECTIVE: To describe seafood consumption patterns in First Nations (FN) in
      British Columbia (BC) and examine lifestyle characteristics associated with
      seafood consumption; to identify the top ten most consumed seafood species and
      their contributions to EPA and DHA intake; and to estimate dietary exposure to
      methylmercury, polychlorinated biphenyls and dichlorodiphenyldichloroethylene.
      DESIGN: Dietary and lifestyle data from the First Nations Food Nutrition and
      Environment Study, a cross-sectional study of 1103 FN living in twenty-one
      communities across eight ecozones in BC, Canada, were analysed. Seafood
      consumption was estimated using a traditional FFQ. Seafood samples were analysed
      for contaminant contents. RESULTS: Seafood consumption patterns varied
      significantly across BC ecozones reflecting geographical diversity of seafood
      species. The top ten most consumed species represented 64 % of total seafood
      consumption by weight and contributed 69 % to the total EPA+DHA intake. Mean
      EPA+DHA intake was 660.5 mg/d in males, 404.3 mg/d in females; and 28 % of FN met
      the Recommended Intake (RI) of 500 mg/d. Salmon was the most preferred species.
      Seafood consumption was associated with higher fruit and vegetable consumption,
      lower smoking rate and increased physical activity. Dietary exposure to selected
      contaminants from seafood was negligible. CONCLUSIONS: In FN in BC, seafood
      continues to be an essential part of the contemporary diet. Seafood contributed
      significantly to reaching the RI for EPA+DHA and was associated with a healthier
      lifestyle. Given numerous health benefits, seafood should be promoted in FN.
      Efforts towards sustainability of fishing should be directed to maintain and
      improve access to fisheries for FN.

PMID- 30215342
TI  - Cardiovascular risk factors in relation to dietary patterns in 50-year-old men
      and women: a feasibility study of a short FFQ.
AB  - OBJECTIVE: We aimed to assess the feasibility of a simple new fifteen-item FFQ as
      a tool for screening risk of poor dietary patterns in a healthy middle-aged
      population and to investigate how the results of the FFQ correlated with
      cardiovascular risk factors and socio-economic factors. DESIGN: A randomized
      population-based cross-sectional study. Metabolic measurements for cardiovascular
      risk factors and information about lifestyle were collected. A fifteen-item FFQ
      was created to obtain information about dietary patterns. From the FFQ, a healthy
      eating index was created with three dietary groups: good, average and poor.
      Multivariate logistic regression was used to assess relationships between dietary
      patterns and cardiovascular risk factors. SETTING: Sweden. SUBJECTS: Men and
      women aged 50 years and living in Gothenburg, Sweden. RESULTS: In total, 521
      middle-aged adults (257 men, 264 women) were examined. With good dietary pattern
      as the reference, there was a gradient association of having obesity,
      hypertension and high serum TAG in those with average and poor dietary patterns.
      After adjustment for education and lifestyle factors, individuals with a poor
      dietary pattern still had significantly higher risk (OR; 95 % CI) of obesity
      (2.33; 1.10, 4.94), hypertension (2.73; 1.44, 5.20) and high serum TAG (2.62;
      1.33, 5.14) compared with those with a good dietary pattern. CONCLUSIONS:
      Baseline data collected by a short FFQ can predict cardiovascular risk factors in
      middle-aged Swedish men and women. The FFQ could be a useful tool in health-care
      settings, when screening for risk of poor dietary patterns.

PMID- 30215344
TI  - HIV criminalisation is bad policy based on bad science.

PMID- 30215343
TI  - Functional Transcriptomics for Bacterial Gene Detectives.
AB  - Developments in transcriptomic technology and the availability of whole-genome
      level expression profiles for many bacterial model organisms have accelerated the
      assignment of gene function. However, the deluge of transcriptomic data is making
      the analysis of gene expression a challenging task for biologists. Online
      resources for global bacterial gene expression analysis are not available for the
      majority of published data sets, impeding access and hindering data exploration.
      Here, we show the value of preexisting transcriptomic data sets for hypothesis
      generation. We describe the use of accessible online resources, such as SalComMac
      and SalComRegulon, to visualize and analyze expression profiles of coding genes
      and small RNAs. This approach arms a new generation of "gene detectives" with
      powerful new tools for understanding the transcriptional networks of Salmonella,
      a bacterium that has become an important model organism for the study of gene
      regulation. To demonstrate the value of integrating different online platforms,
      and to show the simplicity of the approach, we used well-characterized small RNAs
      that respond to envelope stress, oxidative stress, osmotic stress, or iron
      limitation as examples. We hope to provide impetus for the development of more
      online resources to allow the scientific community to work intuitively with
      transcriptomic data.

PMID- 30215345
TI  - Decline in new HIV diagnoses among MSM in Melbourne.

PMID- 30215346
TI  - Doxycycline use in MSM taking PrEP.

PMID- 30215347
TI  - Scotland's struggle with injection drug use and HIV.

PMID- 30215349
TI  - Glasgow Drugs Crisis Centre providing a safe environment.

PMID- 30215348
TI  - Highlights of AIDS 2018.

PMID- 30215350
TI  - Dr. Ponnandai interviews Dr. Harold Wanebo.

PMID- 30215351
TI  - Drinking to death: the changing face of liver disease.

PMID- 30215352
TI  - Organ donation: presumed consent is not enough.

PMID- 30215353
TI  - Chemotherapy for pancreatic cancer: the rise of multidrug regimens.

PMID- 30215354
TI  - The public health challenge of liver cancer in Mongolia.

PMID- 30215355
TI  - Future directions in therapeutic gastrointestinal endoscopy.

PMID- 30215356
TI  - One step closer to elimination of hepatitis C in Egypt.

PMID- 30215357
TI  - New York State announces initiative to eliminate hepatitis C.

PMID- 30215359
TI  - When clean eating goes dirty.

PMID- 30215360
TI  - Nigeria's complicated hepatitis burden.

PMID- 30215361
TI  - William Arbuthnot Lane: kink catastrophe.

PMID- 30215362
TI  - Emerging non-invasive approaches for diagnosis and monitoring of portal
      hypertension.
AB  - Clinically significant portal hypertension is associated with an increased risk
      of developing gastro-oesophageal varices and hepatic decompensation. Hepatic
      venous pressure gradient measurement and oesophagogastroduodenoscopy are the gold
      standard methods for assessing clinically significant portal hypertension
      (hepatic venous pressure gradient >=10 mm Hg) and gastro-oesophageal varices,
      respectively. However, invasiveness, cost, and feasibility limit their widespread
      use, especially if repeated and serial evaluations are required to assess the
      efficacy of pharmacotherapy. Although new techniques for non-invasive portal
      pressure measurement have been pursued for many decades, only recently have new
      tools been assessed and validated for larger clinical application. This Review
      focuses on the recent advances in non-invasive approaches for the diagnosis and
      serial monitoring of portal hypertension and varices for clinical practice.

PMID- 30215364
TI  - Correction to Lancet Gastroenterol Hepatol 2018; 3: 593-95.

PMID- 30215363
TI  - Idiopathic recurrent acute pancreatitis.
AB  - Idiopathic recurrent acute pancreatitis is clinically challenging and has
      substantial socioeconomic consequences. Investigations are expensive and often
      reveal little about the cause of the disease. Little is known about the
      interaction between genetic, environmental, anatomical, and other factors that
      contribute to the disease. Data on the efficacy, safety, and long-term outcomes
      of endoscopic therapies are scarce. The effect of idiopathic recurrent
      pancreatitis on quality of life is often underestimated. A more thorough
      examination of the causes of the disease and the roles of other associated risk
      factors is needed, as are well designed clinical studies with robust and
      objectively measurable outcomes. Ideally, evaluation of the causes of disease and
      therapy should be done only in specialised centres, should follow a protocol, and
      all outcomes should be formally assessed.

PMID- 30215365
TI  - Slow burn: tobacco control in the Americas.

PMID- 30215366
TI  - Are we ready for universal genomic sequencing for newborns?

PMID- 30215367
TI  - Reducing harm in the treatment of multidrug-resistant tuberculosis.

PMID- 30215368
TI  - Better and safer treatment for multidrug-resistant tuberculosis.

PMID- 30215369
TI  - Offline: Why has global health forgotten cancer?

PMID- 30215370
TI  - Criminalisation of health care in Nicaragua's political crisis.

PMID- 30215371
TI  - India advises against electronic nicotine delivery systems.

PMID- 30215372
TI  - Greece's health after the "day of liberation".

PMID- 30215373
TI  - Anne Chang: a champion of childhood lung health.

PMID- 30215374
TI  - Interpretation of results of pooled analysis of individual patient data.

PMID- 30215375
TI  - Interpretation of results of pooled analysis of individual patient data.

PMID- 30215376
TI  - Interpretation of results of pooled analysis of individual patient data -
      Authors' reply.

PMID- 30215378
TI  - Department of Error.

PMID- 30215377
TI  - Fixed-dose combinations for hypertension.

PMID- 30215379
TI  - Department of Error.

PMID- 30215380
TI  - Department of Error.

PMID- 30215384
TI  - Rhinocerebral aspergillosis.

PMID- 30215382
TI  - Bronchiectasis in children: diagnosis and treatment.
AB  - Bronchiectasis is conventionally defined as irreversible dilatation of the
      bronchial tree. Bronchiectasis unrelated to cystic fibrosis is an increasingly
      appreciated cause of chronic respiratory-related morbidity worldwide. Few
      randomised controlled trials provide high-level evidence for management
      strategies to treat the children affected by bronchiectasis. However, both
      decades-old and more recent studies using technological advances support the
      notion that prompt diagnosis and optimal management of paediatric bronchiectasis
      is particularly important in early childhood. Although considered to be of a non
      reversible nature, mild bronchiectasis determined by radiography might be
      reversible at any age if treated early, and the lung function decline associated
      with disease progression could then be halted. Although some management
      strategies are extrapolated from cystic fibrosis or adult-based studies, or both,
      non-cystic fibrosis paediatric-specific data to help diagnose and manage these
      children still need to be generated. We present current knowledge and an updated
      definition of bronchiectasis, and review controversies relating to the management
      of children with bronchiectasis, including applying the concept of so-called
      treatable traits.

PMID- 30215385
TI  - Robust Hund rule without Coulomb repulsion and exclusion principle in quantum
      antiferromagnetic chains of composite half spins.
AB  - Quantum spin chains with composite spins have been used to approximate
      conventional chains with higher spins. For instance, a spin 1 (or [Formula: see
      text]) chain was sometimes approximated by a chain with two (or three) spin
      [Formula: see text]'s per site. However, little examination has been given as to
      whether this approximation, effectively assuming the first Hund rule per site, is
      valid and why. In this paper, the validity of this approximation is investigated
      numerically. We diagonalize the Hamiltonians of spin chains with a spin 1 and
      [Formula: see text] per site and with two and three spin [Formula: see text]'s
      per site. The low energy excitation spectrum for the spin chain with M spin
      [Formula: see text]'s per site is found to coincide with that of the
      corresponding conventional chain with one spin [Formula: see text] per site. In
      particular, we find that as the system size increases, an increasingly larger
      block of consecutive lowest energy states with maximal spin per site is observed,
      robustly supporting the first Hund rule even though the exclusion principle does
      not apply and the system does not possess Coulomb repulsion. As for why this
      approximation works, we show that this effective Hund rule emerges as a plausible
      consequence when applying to composite spin systems the Lieb-Mattis theorem,
      which is originally for the ground state of ferrimagnetic and antiferromagnetic
      spin systems.

PMID- 30215386
TI  - Electronic structure of Pr2MnNiO6 from x-ray photoemission, absorption and
      density functional theory.
AB  - The electronic structure of double perovskite Pr2MnNiO6 was studied using core x
      ray photoelectron spectroscopy and x-ray absorption spectroscopy. The 2p x-ray
      absorption spectra show that Mn and Ni are in 4+  and 2+  states respectively.
      Based on charge transfer multiplet analysis of the 2p XPS spectra of both ions,
      we find charge transfer energies [Formula: see text] of 3.5 and 2.5 eV for Ni and
      Mn respectively. The ground state of Ni2+ and Mn4+ ions reveal a higher d
      electron count of 8.21 and 3.38 respectively as compared to the ionic values. The
      partial density of states clearly show a charge transfer character of the system
      for U  -  J [Formula: see text] 2 eV. The O 1s edge absorption spectra reveal a
      band gap of 0.9 eV, which is close to the value estimated from analysis of Ni and
      Mn 2p photoemission and absorption spectra. The combined analysis of nature of
      spectroscopic data and first principles calculations reveal that the material is
      a p  -  d type charge transfer insulator with an intermediate covalent character
      according to the Zannen-Sawatzy-Allen phase diagram.

PMID- 30215388
TI  - Current prescribing trends of antibiotics by dentists in Australia from 2013 to
      2016. Part 1.
AB  - Improving antibiotic stewardship by dentists may help.

PMID- 30215383
TI  - Advances in bronchiectasis: endotyping, genetics, microbiome, and disease
      heterogeneity.
AB  - Bronchiectasis is characterised by pathological dilation of the airways. More
      specifically, the radiographic demonstration of airway enlargement is the common
      feature of a heterogeneous set of conditions and clinical presentations. No
      approved therapies exist for the condition other than for bronchiectasis caused
      by cystic fibrosis. The heterogeneity of bronchiectasis is a major challenge in
      clinical practice and the main reason for difficulty in achieving endpoints in
      clinical trials. Recent observations of the past 2 years have improved the
      understanding of physicians regarding bronchiectasis, and have indicated that it
      might be more effective to classify patients in a different way. Patients could
      be categorised according to a heterogeneous group of endotypes (defined by a
      distinct functional or pathobiological mechanism) or by clinical phenotypes
      (defined by relevant and common features of the disease). In doing so, more
      specific therapies needed to effectively treat patients might finally be
      developed. Here, we describe some of the recent advances in endotyping, genetics,
      and disease heterogeneity of bronchiectasis including observations related to the
      microbiome.

PMID- 30215387
TI  - One-Pot Facile Fabrication of Bioavailable Iron Nanoparticles with Good
      Biocompatibility for Anemia Therapy.
AB  - BACKGROUND Iron deficiency anemia (IDA) has been a major public health problem
      all over the world. Developing new iron (Fe) fortificants with both high
      bioavailability and negligible food sensory changes for IDA is in urgent demand.
      MATERIAL AND METHODS The Fe nanoparticles were fabricated through a one-pot
      reduction process under the protection of bovine serum albumin (BSA). The BSA-Fe
      nanoparticles were characterized systematically. The comparisons between BSA-Fe
      nanoparticles and FeSO4 in bioavailability were carried out through hemoglobin
      (Hb) repletion method. The biocompatibility of BSA-Fe nanoparticles was also
      investigated through in vitro and in vivo assays. RESULTS BSA-Fe nanoparticles
      have super-small size and good water solubility as well as water stability. The
      Hb repletion assay demonstrated that BSA-Fe nanoparticles have comparative
      bioavailability with FeSO4. The in vitro cell viability assay, in vivo
      histological analysis, and biochemical measurements proved the remarkable
      biocompatibility of BSA-Fe nanoparticles. CONCLUSIONS The BSA-Fe nanoparticles
      fabricated through a one-pot facile method have good water solubility,
      comparative bioavailability with FeSO4, and acceptable biocompatibility,
      exhibiting good potential for further clinical translations.

PMID- 30215381
TI  - Treatment correlates of successful outcomes in pulmonary multidrug-resistant
      tuberculosis: an individual patient data meta-analysis.
AB  - BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor.
      We aimed to estimate the association of treatment success and death with the use
      of individual drugs, and the optimal number and duration of treatment with those
      drugs in patients with multidrug-resistant tuberculosis. METHODS: In this
      individual patient data meta-analysis, we searched MEDLINE, Embase, and the
      Cochrane Library to identify potentially eligible observational and experimental
      studies published between Jan 1, 2009, and April 30, 2016. We also searched
      reference lists from all systematic reviews of treatment of multidrug-resistant
      tuberculosis published since 2009. To be eligible, studies had to report original
      results, with end of treatment outcomes (treatment completion [success], failure,
      or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised
      individual patient data from eligible studies, provided by study investigators,
      regarding clinical characteristics, treatment, and outcomes. Using propensity
      score-matched generalised mixed effects logistic, or linear regression, we
      calculated adjusted odds ratios and adjusted risk differences for success or
      death during treatment, for specific drugs currently used to treat multidrug
      resistant tuberculosis, as well as the number of drugs used and treatment
      duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346
      (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%)
      died. Compared with failure or relapse, treatment success was positively
      associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11
      to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21),
      moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and
      clofazimine (0.06, 0.01 to 0.10). There was a significant association between
      reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (
      0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (
      0.14, -0.19 to -0.10). Compared with regimens without any injectable drug,
      amikacin provided modest benefits, but kanamycin and capreomycin were associated
      with worse outcomes. The remaining drugs were associated with slight or no
      improvements in outcomes. Treatment outcomes were significantly worse for most
      drugs if they were used despite in-vitro resistance. The optimal number of
      effective drugs seemed to be five in the initial phase, and four in the
      continuation phase. In these adjusted analyses, heterogeneity, based on a
      simulated I2 method, was high for approximately half the estimates for specific
      drugs, although relatively low for number of drugs and durations analyses.
      INTERPRETATION: Although inferences are limited by the observational nature of
      these data, treatment outcomes were significantly better with use of linezolid,
      later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for
      treatment of multidrug-resistant tuberculosis. These findings emphasise the need
      for trials to ascertain the optimal combination and duration of these drugs for
      treatment of this condition. FUNDING: American Thoracic Society, Canadian
      Institutes of Health Research, US Centers for Disease Control and Prevention,
      European Respiratory Society, Infectious Diseases Society of America.

PMID- 30215389
TI  - Occlusion: Time to debate malocclusion.

PMID- 30215390
TI  - Are dentists' phones a threat to patients?
AB  - Dentists' perceptions of smart phone use in the clinical environment 2018; 225:
      320-324 http://dx.doi.org/10.1038/sj.bdj.2018.642.

PMID- 30215391
TI  - Improved online shopping for dentistry needs.

PMID- 30215392
TI  - An investigation of general dental practitioners' understanding and perceptions
      of minimally invasive dentistry.

PMID- 30215393
TI  - The key to a pearly white smile.

PMID- 30215395
TI  - Key to success.

PMID- 30215394
TI  - Restoration longevity: New treatment plan.

PMID- 30215397
TI  - Professorial roles for dentists fall 8.3% since 2015.

PMID- 30215396
TI  - Acquire the dento-legal support you need.

PMID- 30215398
TI  - The perfect smile - Part 1.

PMID- 30215399
TI  - Dentists working for corporates feel less in control.

PMID- 30215400
TI  - Smart toothbrush to make brushing fun for kids.

PMID- 30215401
TI  - Dental trauma: Trauma protocol for schools.

PMID- 30215402
TI  - Combining aesthetics and functionality.

PMID- 30215403
TI  - Ireland set to adopt HPV vaccine for teenage boys policy.

PMID- 30215404
TI  - Animal magic is helping patients enjoy their trip to the dentist.

PMID- 30215405
TI  - Complaints about dental practitioners: an analysis of 6 years of complaints about
      dentists, dental prosthetists, oral health therapists, dental therapists and
      dental hygienists in Australia.
AB  - Dentists receive more complaints than other health practitioners.

PMID- 30215406
TI  - Dentists on film: Pearl Harbor.

PMID- 30215407
TI  - Dentist morale falling alongside dwindling income.

PMID- 30215409
TI  - Five-year survival of short single-tooth implants (6 mm): a randomized controlled
      clinical trial.
AB  - Shorter implants are a reasonable option.

PMID- 30215408
TI  - Evidence, it's good for you.
AB  - Disseminating research evidence: what matters to general dental practitioners?
      2018; 225: 413-417 http://dx.doi.org/10.1038/sj.bdj.2018.737.

PMID- 30215410
TI  - Quality water essential to decontamination outcomes.

PMID- 30215411
TI  - Expert help in root canal treatment.

PMID- 30215412
TI  - New injectable restorative claims to be strong as a rock.

PMID- 30215413
TI  - What's your philosophy - maximally destructive or minimally invasive dentistry?
AB  - An investigation of general dental practitioners' understanding and perceptions
      of minimally invasive dentistry.

PMID- 30215414
TI  - Lighting the way for preventive dentistry.

PMID- 30215415
TI  - A new world of diagnostic possibilities.

PMID- 30215416
TI  - Associates and their working environment: a comparison of corporate and non
      corporate associates.
AB  - Introduction The share of the dental market held by corporate bodies continues to
      increase. With the profession currently facing many challenges it is important to
      understand their place in the profession and their effect.Aim This exploratory
      study aims to provide an insight into dental associates in relation to their
      working environment. Specifically, the differences between working in corporate
      and non-corporate environments in England.Materials and methods Secondary
      analysis of a self-report questionnaire examining demographics, pay, working
      conditions, job satisfaction and morale using a combination of closed and open
      ended responses sent to randomly selected associate dentists who are BDA members.
      Responses from associates working in England solely in either the corporate or
      non-corporate sector were analysed.Results Significant differences were seen
      between associates working in corporate practice when compared to those in non
      corporates practice, for example, significantly less corporate associates were
      female and corporate associates reported relatively lower levels of autonomy and
      control.Discussion The differences seen between sectors could be related to
      rationalisation and should this be the reality it could have far reaching effects
      on the profession and its ability to manage itself.Conclusion This study
      highlights some differences between the corporate and non-corporate dental
      sectors. Further work is needed to build a deeper understanding of the sector.

PMID- 30215417
TI  - Trust in adhesive excellence.

PMID- 30215418
TI  - New name, same first-class experience.

PMID- 30215419
TI  - Dental research: International research collaboration.

PMID- 30215420
TI  - James George Steele CBE.

PMID- 30215421
TI  - Future plans for the BDA Benevolent Fund.

PMID- 30215422
TI  - Correction: Coronectomy: Coronectomy & CBCT - A marriage of convenience!
AB  - This corrects the article DOI: 10.1038/sj.bdj.2018.657.

PMID- 30215423
TI  - Dental care may benefit patients set for cancer surgery.

PMID- 30215424
TI  - Plug and play electric micromotor boost available.

PMID- 30215425
TI  - An up to 50-year follow-up of crown and veneer survival in a dental practice.
AB  - The retrospective review from a single dental practitioner and laboratory.

PMID- 30215426
TI  - Reliable defence for rugby players.

PMID- 30215428
TI  - Life-long learning to improve your skills.

PMID- 30215427
TI  - Largest oral HPV study in England shows lower than expected infection rates.

PMID- 30215429
TI  - MPs say relax rules over use of e-cigarettes to tackle 'deadly' smoking.

PMID- 30215430
TI  - Dental care for homeless issue attracts BDA controversy.

PMID- 30215431
TI  - ADI Team Congress 2019 details announced.

PMID- 30215432
TI  - Has common sense prevailed?

PMID- 30215433
TI  - Curasept ADS the first 'non-staining' chlorhexidine supported by clinical
      evidence.

PMID- 30215434
TI  - Patient and dentists' interests matter.

PMID- 30215435
TI  - From open packing to negative wound pressure therapy: A critical overview of deep
      sternal wound infection treatment strategies after cardiac surgery.
AB  - Deep sternal wound infection is a challenging aspect of modern cardiac surgery.
      The considerable mortality rate, devastating morbidity and, negative impact on
      long-term survival has driven cardiac and plastic surgeons to seek a more
      advantageous treatment solution. This review summarizes progress in the field of
      deep sternal wound infection treatment after cardiac surgery. Emphasis is placed
      on outcomes analysis of contemporary treatment strategy based on negative
      pressure wound therapy followed by sternotomy wound reconstruction, and its
      comparison with conventional treatment modalities used afore. Furthermore,
      complications and drawbacks of treatment strategies are critically evaluated to
      outline current options for successfully managing this life-threatening
      complication following cardiac surgery.

PMID- 30215436
TI  - Comparison of different methods of ABI acquisition for detection of peripheral
      artery disease in diabetic patients.
AB  - BACKGROUND: Ankle brachial index (ABI) is the principal screening method for
      peripheral arterial disease (PAD). In this study, we compare various types of
      Doppler-derived and oscillometric ABIs with results obtained through duplex
      ultrasonography. METHODS: 62 patients were enrolled in the study. For each limb,
      blood pressures for both ankle arteries and the arm were measured using Doppler
      and an automated oscillometric device. Duplex ultrasound was performed for all
      limbs and occlusions >50% were considered PAD-positive. ABI was calculated using
      both higher (HABP) and lower (LABP) arterial blood pressure on the individual
      limbs and the ability to predict duplex-detected stenoses was evaluated. RESULTS:
      LABP calculation provided results superior to the guideline-recommended HABP.
      Considering patients with ABI >1.4 or measurement failure as PAD-positive further
      enhanced the test parameters. The higher ABI cut-off of 1.0 resulted in somewhat
      better sensitivities (max 92%) and negative predictive values (max 87%) at the
      expense of a substantial increase in the number of false positives. Oscillometric
      method yielded poor sensitivities but very good specificities (max 94%) and
      positive predictive values (max 90%). CONCLUSIONS: Doppler-based LABP provides
      better results than the guideline-recommended HABP in diabetic patients,
      nevertheless even this method is not perfect. Increasing the cut-off value to 1.0
      in these patients does not bring a substantial improvement of the test
      performance. Patients with high ABI should be automatically considered PAD
      positive and referred for further investigation using imaging techniques.

PMID- 30215437
TI  - Conjugate addition from the excited state.
AB  - Conjugate addition occurs efficiently from excited hydrazide based acrylanilides
      under both UV and metal free visible light irradiations. The reaction proceeds
      via an excited state encounter complex that bifurcates either via an electron or
      energy transfer pathway. The generality of excited state conjugate addition is
      demonstrated using chloromethylation and by thiol addition.

PMID- 30215438
TI  - Construction of a diverse set of terpenoid decalin subunits from a common
      enantiomerically pure scaffold obtained by a biomimetic cationic cyclization.
AB  - An unprecedented biomimetic cationic cyclization reaction of an alkyne-containing
      geraniol-derived epoxide is used for the stereoselective synthesis of a novel
      enantiomerically pure scaffold that is easily transformed into a set of
      structurally diverse decalin derivatives with potential application in the
      synthesis of targeted natural products and/or natural-product-inspired new
      molecules.

PMID- 30215439
TI  - Organelle-specific analysis of labile Fe(ii) during ferroptosis by using a
      cocktail of various colour organelle-targeted fluorescent probes.
AB  - Ferroptosis is an emerging type of cell death mode that is dependent on iron.
      Unfortunately, the detailed analysis of the function of organelle labile Fe(ii)
      in oxidative damage and lethality of the cells has not been demonstrated so far,
      mainly due to the lack of efficient methods to visualize labile Fe(ii) at the
      targeted organelles. We have recently reported a series of Fe(ii)-selective
      fluorescent probes, i.e., Ac-MtFluNox, Lyso-RhoNox, and ER-SiRhoNox, which can
      detect Fe(ii) specifically in the mitochondria, lysosomes, and endoplasmic
      reticulum (ER), respectively. These probes demonstrate similar reaction rates and
      off/on contrasts with various colours and intracellular distributions, enabling
      simultaneous multi-colour imaging that allows the monitoring of labile Fe(ii)
      levels at each targeted organelle. In this paper, by using a cocktail of these
      probes, we successfully visualised the aberrant elevation of labile Fe(ii) in the
      lysosomes and ER prior to HT1080 cell death induced by erastin, which is an
      inducer of ferroptosis.

PMID- 30215440
TI  - The effect of linker DNA on the structure and interaction of nucleosome core
      particles.
AB  - In eukaryotes, the compaction of chromatin fibers composed of nucleosome core
      particles (NCPs) connected by a linker DNA into chromosomes is highly efficient;
      however, the underlying folding mechanisms remain elusive. We used small angle X
      ray scattering (SAXS) to investigate the influence of linker DNA length on the
      local structure and the interparticle interactions of the NCPs. In the presence
      of the linker DNA of 30 bp or less in length, the results suggest partial
      unwrapping of nucleosomal DNA on the NCP irrespective of the linker DNA length.
      Moreover, the presence of 15 bp linker DNA alleviated the electrostatic repulsion
      between the NCPs and prevented the formation of an ordered columnar hexagonal
      phase, demonstrating that the linker DNA plays an active role in chromatin
      folding.

PMID- 30215441
TI  - Correction: Compressible colloidal clusters from Pickering emulsions and their
      DNA functionalization.
AB  - Correction for 'Compressible colloidal clusters from Pickering emulsions and
      their DNA functionalization' by In-Seong Jo et al., Chem. Commun., 2018, 54, 8328
      8331.

PMID- 30215442
TI  - Rare-earth-doped fluoride nanoparticles with engineered long luminescence
      lifetime for time-gated in vivo optical imaging in the second biological window.
AB  - Biomedicine is continuously demanding new luminescent materials to be used as
      optical probes for the acquisition of high resolution, high contrast and high
      penetration in vivo images. These materials, in combination with advanced
      techniques, could constitute the first step towards new diagnosis and therapy
      tools. In this work, we report on the synthesis of long lifetime rare-earth-doped
      fluoride nanoparticles by adopting different strategies: core/shell and dopant
      engineering. The here developed nanoparticles show intense infrared emission in
      the second biological window with a long luminescence lifetime close to 1
      millisecond. These two properties make the here presented nanoparticles excellent
      candidates for time-gated infrared optical bioimaging. Indeed, their potential
      application as optical imaging contrast agents for autofluorescence-free in vivo
      small animal imaging has been demonstrated, allowing high contrast real-time
      tracking of gastrointestinal absorption of nanoparticles and transcranial imaging
      of intracerebrally injected nanoparticles in the murine brain.

PMID- 30215444
TI  - [Lifelong learning: towards flexible training for the psychiatrist of the
      future].

PMID- 30215443
TI  - [Where do you go, psychiatrist?]

PMID- 30215445
TI  - [Psychiatry and fenomenology: a thorny issue].

PMID- 30215447
TI  - [The reliability of Delta-T].
AB  - BACKGROUND: In Dutch mental health care there is an ongoing debate about the
      benefits of rom and utility of benchmarking. Opinions vary regarding the
      reliability and validity of performance indicators.<br/> AIM: Investigation of
      the reliability of the main indicator of Foundation Benchmark Mental Health Care
      (sbg), Delta-T, the indicator of treatment outcome.<br/> METHOD: The reliability
      was established with two indices: the intraclass correlation coefficient (icc)
      for the agreement between repeated assessments of average treatment outcome and
      the consistency in rank order of mental health care providers over time.<br/>
      RESULTS: The reliability of Delta-T proved to be excellent.<br/> CONCLUSION:
      Reliability is a basic requirement, but only the first step in establishing the
      utility of Delta-T. Further investigation of its validity is ongoing, especially
      on how robust treatment outcome is for bias due to instrumentation, selection,
      and confounding by casemix composition. Ultimately, the usefulness of treatment
      outcome as indicator of quality of care needs to be demonstrated in practice.

PMID- 30215446
TI  - [Data-guided learning from suicidal incidents by using KEHR SUICIDE. A practice
      example in a Dutch mental health care facility].
AB  - BACKGROUND: Specific and systematic data on health care providers' behaviour is
      needed to futher improve the care provided to suicidal patients in mental health
      care facilities.<br/> METHOD: Explorative observational study of all suicidal
      incidents (n=50) that occurred in a Dutch mental health care facility over a one
      year period. Incidents were evaluated using KEHR SUICIDE, a questionnaire that
      assesses to what extent health care providers' conduct was compliant to the
      suicide practice guideline in the context of patients' suicidal behaviour.
      Associations between health care providers' and patients' features and guideline
      compliant behaviours of health care providers were calculated by logistic
      regression models.<br/> RESULTS: Health care providers showed less guideline
      compliant behaviour when the patient had a psychotic, substance abuse or
      development disorder or had no axis 1 disorder. A positive association was found
      between guideline compliant behaviour and the extent to which the incident had
      been expected. CONCLUSION Guideline compliant behaviour of mental health care
      providers appears to be related to the axis 1 disorder of patients in a Dutch
      mental health care facility. Still, the application of guideline compliant
      behaviour concerning suicide incidents shows room for improvement. KEHR SUICIDE
      is shown to be a helpful tool for multidisciplinary evaluation of suicidal
      incidents as it provides specific, ready-made information by which mental health
      care facilities can guide, examine and adjust suicide prevention policy. The
      outcomes provide hypotheses that may be examined in future research.

PMID- 30215448
TI  - [Discrepancies in reported medication use in elderly psychiatric outpatients].
AB  - BACKGROUND: Different fields of study have revealed discrepancies between the
      reported medication use presented by patients and medical records held by their
      doctor or apothecary. These also appear to have clinically relevant consequences.
      At present only two studies have explored medication discrepancies in
      psychiatry.<br/> AIM: To investigate the occurrence of discrepancies in the
      reported medication use of a psychiatric elderly out-patient population.<br/>
      METHOD: Comparing 40 medication records of patients to their respective general
      practitioner and pharmacy records. Information on their social situation, Mini
      Mental State Examination score and diagnosis was collected.<br/> RESULTS: One or
      more discrepancies were present in 80 percent of cases. Patients living alone had
      a higher percentage of discrepancies. Patients with cognitive problems or a low
      score on the Mini-Mental State Examination had less discrepancies.<br/>
      CONCLUSION: Medication discrepancies are also common in a psychiatric elderly
      outpatient population.

PMID- 30215449
TI  - [The Klinefelter syndrome: a systematic review of secondary psychiatric
      comorbidities].
AB  - BACKGROUND Klinefelter syndrome (ks) is the most common type of sex chromosome
      aneuploidy and is associated with psychiatric comorbidities. ks is only diagnosed
      in less than half of the cases due to the heterogeneous phenotype.<br/> AIM: This
      study investigates the prevalence of secondary psychiatric diseases and their
      treatment in ks patients.<br/> METHOD: Relevant articles were identified using
      the PubMed database. We included articles published in the last ten years,
      concerning ks patients who were assessed for comorbidities.<br/> RESULTS: A total
      of 50 articles were included. The most prevalent comorbidities were language
      disorders and autism spectrum symptoms. Only half the ks population was treated
      (50.4%) with the primary treatment consisting of hormone therapy. 14% of patients
      were never treated hormonally.<br/> CONCLUSION: Psychiatric comorbidities were
      observed in many patients with ks. The early diagnosis of ks in patients is
      important, given that inadequate treatment of ks patients can lead to reduced
      social functioning.

PMID- 30215450
TI  - [Does psychiatry revert to subjectivity?]
AB  - BACKGROUND: Psychiatry is currently challenged by two main issues, subjectivity
      and non-exclusivity.<br /> AIM: The re-appraisal of phenomenological
      psychiatry.<br /> METHOD: Personal reflection. <br /> RESULTS: Phenomenology may
      contribute to psychiatry by 1. offering a method, 2. focusing on descriptive
      observation, and 3. taking a neutral stance.<br /> CONCLUSION: By emphasizing the
      subjective experience, phenomenology offers psychiatry an opportunity to become
      proficient and to distinguish itself from other disciplines through the continued
      development of insight and understanding of mental disorders.

PMID- 30215451
TI  - [The patient's perspective on the self-management and professional treatment of
      depression].
AB  - BACKGROUND: More than two-thirds of all patients suffering from depression
      experience insufficient improvement despite treatment. Self-management strategies
      and treatment objectives should be more in line with what patients consider to be
      helpful. This would improve the treatment efficacy of domains relevant to
      patients and allow for self-management of depression where possible.<br/> AIM: To
      explore the patient's perspective on self-management and professional treatment
      for depression.<br/> METHOD: Predominantly qualitative methods: in-depth
      individual interviews, concept mapping (mixed method) and a nationwide self
      report survey.<br/> RESULTS: Participants generated 50 self-management strategies
      addressing themes such as engaging in activities (e.g. 'leaving the house
      regularly'), focus on the diagnosis depression (e.g. 'acceptation') and treatment
      (e.g. 'trusting the therapist'), remaining socially engaged (e.g. 'informing
      family about the depression') and good structure and self-care (e.g. 'setting
      realistic goals'). A lack of clarity and consensus about either the nature of the
      depression or the content of treatment and a precarious relationship with the
      professional were perceived as impeding characteristics of treatment.<br/>
      CONCLUSION: Patients appear to be able to contribute actively and in various ways
      when managing their own mental health. By exploring the patient's perspectives,
      professionals could offer treatment established through shared goals.

PMID- 30215453
TI  - [Reaction on 'Admission to child and adolescent psychiatry: how do we provide for
      the right to a confidential advisor?']

PMID- 30215452
TI  - [Suicide by a psychiatry resident - reflection and postvention].
AB  - BACKGROUND: After the suicide of a psychiatry resident, the coordinators of her
      trainee program had to face several questions.<br/> AIM: To articulate some of
      the main questions and to describe our course of action as a way of 'suicide
      postvention'.<br/> METHOD: Reflection on an anonymized residency situation.<br/>
      RESULTS: The central question pertained to the dilemma whether the coordinator,
      supervisor, or other residents should consider the situation from a therapist
      viewpoint or as employer-colleague. The last option was formally the most valid,
      but the dilemma related to other questions, such as about our professional
      identity as psychiatrists. Postvention occurred in several phases (immediate,
      recovery, reconstruction) and included several meetings with the residents and
      supervisors. One meeting was facilitated by the spiritual counseler of the
      institution.<br/> CONCLUSION: A self-critical approach and our postvention
      approach seemed to supply a need of attention and care for all residency
      colleagues involved.

PMID- 30215454
TI  - [Screening for metabolic syndrome in older patients with severe mental illness].
AB  - BACKGROUND: Diabetes, cardiovascular disease and metabolic syndrome are more
      prevalent in older patients with severe mental illness (smi) than in healthy
      older persons in the same age-group as the smi patients. Compared to the general
      population, smi patients are often in a poorer state of (physical) health and
      have a shorter life expectancy.<br/> AIM: To assess the value of screening older
      smi patients (>= 60) for metabolic syndrome.<br/> METHOD: We performed a
      prospective evaluation of the metabolic screening outcome data relating to 100
      older smi patients and 124 healthy older patients and compared the results.<br/>
      RESULTS: In our smi patients (average age 69 years; 52% bipolar disorder, 48%
      schizophrenia) the frequency of metabolic syndrome (43%) was no higher than in
      healthy older persons (39.5%, p = 0.60). However, in 51% of the smi sample,
      metabolic screening detected at least one metabolic abnormality in a patient with
      no previous history for that specific parameter.<br/> CONCLUSION: By making
      routine metabolic screening available to a greater number of older smi patients,
      we should be able to identify substantial numbers of metabolic abnormalities that
      have been previously overlooked.

PMID- 30215455
TI  - ?

PMID- 30215456
TI  - Roles of microRNAs during glioma tumorigenesis and progression.
AB  - Glioma is the most common and aggressive type of brain tumor. It has a poor
      prognosis and a high recurrence rate. Despite continued advances in surgery,
      chemotherapy and radiotherapy, the clinical outcomes remain dismal. MicroRNAs
      (miRNAs) play important roles in the initiation and progression of a multitude of
      tumors. Until now, the molecular mechanism that is responsible for glioma
      tumorigenesis and progression remains unclear. Increasing evidence has shown that
      miRNAs play an important role in glioma. In this review, we focus on the current
      advances in determining the role of miRNAs in regulating tumorigenesis and the
      progression of glioma. In addition, the relevant roles of miRNAs about the
      diagnosis and target therapy have been clarified.

PMID- 30215457
TI  - The functional role of chondrogenic stem/progenitor cells: novel evidence for
      immunomodulatory properties and regenerative potential after cartilage injury.
AB  - Considering the poor intrinsic healing potential of articular cartilage, resident
      chondrogenic stem/progenitor cells (CSPCs) have gained attention in recent years.
      Although, CSPCs are attracted by a cartilage injury, knowledge about the post
      traumatic behaviour and functional role of this cell population is fairly basic.
      The present study, not only elaborated on the regenerative capacities of CSPCs,
      but also illuminated potential immunomodulatory properties after cartilage
      trauma. Estimation of the CSPC population size within previously impacted
      cartilage explants by flow-cytometry revealed an increased percentage of CSPC
      marker positive cells as compared to unimpacted tissue. In line with this,
      proliferation, chemotactic migration and in vitro wound healing activity of
      isolated CSPCs was similarly enhanced after stimulation with trauma-conditioned
      (TC) medium. Further, a significant increase in pro- and anti-inflammatory gene
      expression, as well as IL-6 secretion due to TC-medium-stimulation was measured.
      In this context, antioxidative or chondroanabolic therapeutic intervention
      alleviated the post-traumatic response of TC-medium-activated CSPCs and
      substantially influenced CSPC chondrogenic differentiation in different ways.
      Overall, this study provided novel insights concerning the functional role of
      CSPCs after cartilage trauma and the effects of a therapeutic intervention in
      order to improve regenerative processes and prevent cartilage degeneration
      following trauma.

PMID- 30215458
TI  - Fresh versus frozen-thawed blastocyst transfer in high responders.
AB  - OBJECTIVE: This study aimed to investigate and compare the pregnancy and live
      birth rates in IVF cycles of frozen-thawed embryo transfers and fresh embryo
      transfers in a group of women with a high risk of Ovarian hyperstimulation
      syndrome (OHSS). MATERIAL AND METHODS: The study group consisted of 254 women
      with a high level of response to controlled ovarian hyperstimulation. The
      patients who received fresh cycle embryo transfers with calcium infusions are
      referred to as the Fresh Ca+ group, and those without the calcium therapy are
      called the Fresh Ca- group; and we used correspondingly similar terminology for
      the Frozen group. RESULTS: We observed no statistically significant differences
      between the cycles of fresh and frozen-thawed embryo transfers in patients with a
      high risk of OHSS in terms of implantation, clinical pregnancy, and live birth
      rates. Furthermore, these implantation, clinical pregnancy and live birth rates
      were not different in the cycles with or without calcium treatment. There was no
      statistical difference in the OHSS rates between the fresh and frozen-thawed
      cycles; although, the OHSS rates were less in the two calcium infusion groups
      (Fresh Ca+ and Frozen-thawed Ca+) than in the without-calcium group. There was no
      OHSS development in the subjects of the Frozen-thawed Ca+ group. CONCLUSION: Our
      study results suggest that fresh and frozen-thawed embryo transfers have similar
      IVF results in patients with a high risk of OHSS. Calcium infusion is beneficial
      in preventing OHSS without altering pregnancy rates. Both IVF protocols with
      calcium infusion can safely be applied in high-responder patients without
      lowering success rates.

PMID- 30215459
TI  - Serum levels of circulating miRNA-21, miRNA-10b and miRNA-200c in triple-negative
      breast cancer patients.
AB  - INTRODUCTION: Breast cancer can be classified into five subtypes based on
      variations in the status of three hormonal receptors that are responsible for the
      cancer's heterogeneity: estrogen receptor (ER), progesterone receptor (PR), and
      human epidermal growth factor receptor 2 (HER2). These classifications influence
      the choice of therapies (either neoadjuvant or adjuvant), and the range of
      prognoses, from good (luminal A subtype) to poor (triple-negative cancers).
      OBJECTIVE: The aim of the study was to compare the serum concentration of
      selected miRNAs (miRNA-21, miRNA-10b, and miRNA-200c) between in two groups of
      breast cancer patients with differing ER, PR, and HER2 statuses. MATERIALS AND
      METHODS: The study was performed on two groups of patients. One group (TNBC)
      consisted of patients with triple-negative cancer, and the other group
      (ER(+)/PR(+)) was comprised of patients with positive ER and PR receptors.
      RESULTS: The mean level of miRNA-200c was significantly higher in the ER(+)/PR(+)
      group than in the TNBC group (p < 0.05). No statistically significant difference
      was found between the two groups with regard to the mean levels of miRNA-21 or
      miRNA-10b. CONCLUSION: The level of miRNA-200c was lower in triple-negative
      patients when compared with the levels in the study's ER/PR positive group.

PMID- 30215460
TI  - The analgesic efficiency of transversus abdominis plane (TAP) block after
      caesarean delivery.
AB  - OBJECTIVES: The ultrasound-guided transversus abdominis plane (TAP) block is a
      supporting method of pain relief after different types of surgical and
      gynecological procedures. The aim of the present study was to evaluate the
      analgesic effects of the TAP-block in patients undergoing caesarean section.
      MATERIAL AND METHODS: 88 women undergoing elective caesarean section under spinal
      anaesthesia were prospectively randomized into two groups. In the first group, an
      ultrasound-guided bilateral TAP block was performed using 40 mL 0.25%
      bupivacaine, while the second group was treated without a regional nerve block.
      Both groups received a standard analgesia protocol with intravenous paracetamol
      administered every 6 hours and intravenous tramadol on-demand, delivered using
      the Patient Controlled Analgesia (PCA) method. Pain intensity was assessed
      according to the visual analogue scale (VAS) directly after the TAP block and at
      3, 6 and 12 hours postoperatively. Any patient complaints and side-effects during
      the postoperative period were recorded. RESULTS: The TAP block resulted in a
      significant reduction of pain intensity using the visual analogue scale after 3,
      6 and 12 hours (p < 0.05) and a significant decrease in tramadol administration
      (p < 0.05) during the first 12 hours postoperatively. No significant differences
      in the heart rate and blood pressure were noted between groups (p > 0.05). There
      were no complications related to the TAP block. CONCLUSIONS: The TAP block is a
      safe and effective adjunctive method of pain relief after caesarean delivery.

PMID- 30215461
TI  - Vulvar cancer recurrence - an analysis of prognostic factors in tumour-free
      pathological margins patients group.
AB  - OBJECTIVES: To evaluate risk factors associated with the local recurrence of
      invasive squamous cell vulvar cancer in patient group with tumor-free
      pathological margins. MATERIAL AND METHODS: This is a retrospective analysis of
      47 patients who underwent surgical treatment at University Hospital Brno, the
      Czech Republic between 2007 and 2014. 24 patients were classified as IB stage and
      three as II stage. A further 20 patients representing stage III showed the
      metastatic involvement of regional lymph nodes. Seven prognostic factors were
      analyzed in relation to local tumour recurrence: tumour size, margin distance,
      depth of invasion, lymphovascular space involvement (LVSI), midline involvement,
      metastatic lymph nodes and FIGO stage. RESULTS: All prognostic factors were found
      to be statistically significant with respect to the risk of local recurrence. The
      highest risk of local recurrence was observed for the depth of invasion > 5 mm
      (HR, 12.42 [95% CI; 3.44-44.84]) and for the presence of LVSI (HR, 10.83 [95% CI;
      3.87-30.28]). The study also established a clear difference in the risk of local
      recurrence between patient groups with resection margin < 8 vs. >= 8 mm (HR, 4.91
      [95% CI; 1.73-13.93; p = 0.003]. CONCLUSIONS: Tumour-free pathological margin of
      >= 8 mm is a major prognostic factor of local recurrence which can be influenced
      by the surgeon. A perfect knowledge of the extent of the disease prior to surgery
      supports adequately radical surgical trends. The emphasis is given on adequate
      radicality as well as on the reduction of overtreatment without worse-ning
      prognosis by simultaneously preserving the quality of life.

PMID- 30215462
TI  - Does Home Birth Reduce the Risk of Pelvic Organ Prolapse?
AB  - OBJECTIVES: To determine the relationship between vaginal birth and the
      development of POP among women who deliv-ered in non-hospital settings (home
      birth). MATERIAL AND METHODS: Data were collected retrospectively from the files
      of patients who presented to a hospital outpatient clinic between April 1, 2011
      and April 1, 2012 with complaints of urinary incontinence, uterine sagging,
      vaginal mass, or vaginal pain. The patients' age, height, weight, body mass
      index, menopause age, number of deliveries, and presence of hypertension and
      diabetes mellitus were noted. Patients whose urogynecologic evaluation included
      POP Quantification (POP-Q) scoring were included in the study. The patients were
      separated into a group of women who had never given birth and another group of
      women with one or more deliveries. RESULTS: Of the 179 patients in the study, 28
      had never given birth and 151 had given birth at least once. The nulliparous
      patients had no cystocele, rectocele, or uterine prolapse. The prevalence rates
      of cystocele, rectocele, and uterine prolapse were significantly higher in the
      multiparous group. Cystocele, rectocele, and uterine prolapse development were
      significantly correlated with number of deliveries, but there was no statistical
      association with age, body mass index, menopausal age, diabetes mellitus, or
      hypertension. univariate analysis reveals that the only factor effective in the
      development of cytocele, rectocele and prolapse is the number of births.
      CONCLUSIONS: Our study suggests that only number of deliveries is associated with
      development of cystocele, rectocele, and uterine prolapse in women who gave birth
      by vaginal route in residential settings.

PMID- 30215463
TI  - The role of osteopontin in the pathogenesis of placenta percreta.
AB  - OBJECTIVE: This study aims to determine how the expression of osteopontin is
      altered in the placenta percreta by compar-ing osteopontin expression in normal
      placentas and placenta percreta tissues. MATERIAL AND METHODS: Placental tissues
      from hysterectomy materials which were histopathologically diagnosed with
      placenta percreta (study group, n = 20) and placental tissues obtained from
      normal term pregnancies (control group, n = 20) were immunohistochemically
      stained with osteopontin antibody. The groups were compared with respect to the
      intensity of cytoplasmic staining for osteopontin. RESULTS: The study and control
      groups were similar with respect to age, gravidity, parity, gestational age at
      birth, number of previous cesarean deliveries and curettages and (p > 0.05 for
      all). Immediate postoperative hemoglobin was significantly lower and the need for
      blood transfusion was significantly higher in the study group (p = 0.001 for
      both). Placental osteo-pontin expression was significantly altered in the study
      group (p = 0.020). Negative staining for placental osteopontin was significantly
      more frequent in the placenta percreta group than the control group (9/20 vs
      0/20, 45.0% vs 0%, p = 0.037). CONCLUSION: As reduced placental osteopontin
      expression was determined in the placenta percreta cases compared to the normal
      term placenta tissues, osteopontin can be considered to have a role in morbidly
      adherent placentation. This study is of value as the first study to investigate
      the changes in osteopontin expression in placenta percreta cases.

PMID- 30215464
TI  - Adipokines and C-peptide in overweight and obese pregnant women.
AB  - OBJECTIVES: The aim of the study was to evaluate the levels of adipokines such as
      adiponectin, resistin, leptin as well as C-peptide in overweight and obese
      pregnant women. MATERIAL AND METHODS: The adipokines and C-peptide concentrations
      were measured in the group of 38 overweight/obese pregnant women (BMI > 25 kg/m2)
      and in 42 pregnant women of normal weight (BMI < 25 kg/m2) with ELISA tests
      between 24th and 34th weeks of gestation. RESULTS: The overweight/obese women
      compared to lean ones were characterized by significantly higher concentrations
      of leptin (43.44 +/- 31.41 vs. 21.29 +/- 12.67 ng/mL, p = 0.0001) and C-peptide
      (2.77 +/- 1.88 vs. 2.25 +/- 1.42 ng/mL, p = 0.034). There were no significant
      differences between groups in resistin (17.39 +/- 7.59 vs. 15.76 +/- 6.64 ng/mL,
      NS) and adiponectin (6.93 +/- 3.52 vs. 8.07 +/- 6.53 MUg/mL, NS) levels. In the
      overweight/obese patients, no relationships between the adipokines, C-peptide and
      CRP concentrations were found. BMI was negatively correlated with the resistin
      levels (R = -0.406, p = 0.011). The significant correlation between leptin and C
      peptide concentrations was observed in the study group (R = 0.517, p = 0.012). In
      the control group, the negative correlation between adiponectin concentrations
      and BMI was shown (R = -0.446, p = 0.003). CONCLUSIONS: The higher levels of
      leptin in the overweight and obese pregnant women seem to reflect the leptin
      resistance condition and the higher levels of C-peptide in this group is
      suggestive for hyperinsulinemia. The positive correlation between C-peptide and
      leptin levels but not with resistin and adiponectin might confirm the role of
      leptin in the hyperinsulinemia development in overweight and obesity during
      pregnancy.

PMID- 30215465
TI  - Skin changes during pregnancy. Is that an important issue for pregnant women?
AB  - OBJECTIVES: The aim of the study was to investigate the prevalence of self
      reported skin complaints during pregnancy, applied treatment and the impact on
      well-being of pregnant women. MATERIAL AND METHODS: We asked 1935 women that were
      maximum 4 years after labor to fill in our questionnaire. The questionnaire
      included questions concerning the course of pregnancy, observed skin lesions,
      applied treatment and influence on the quality of life. RESULTS: Skin changes
      during pregnancy were reported by 1447 patients (74.78%). The prevalence of self
      reported skin complaints were as follows: stretch marks (77.4%), acne (21.6%) and
      recurrent herpes labialis (11.6%). In 43.67% (n = 632) of women who reported
      dermatological problems during pregnancy the disease caused significant
      deterioration in their well-being. Only 168 patients (11.61%) received
      dermatological treatment from their obstetricians. Dermatological con-sultation
      required 217 patients (14.99%). For 133 of treated women (25.68%) the recommended
      treatment was expensive. However, in the majority of patients (379; 73.15%) who
      received treatment the skin changes resolved after therapy. Skin symptoms
      resolved significantly faster in the treated group (3.5 +/- 4.3 week vs 5.8 +/-
      6.2 week; p < 0.001). CONCLUSIONS: Self-reported skin complaints seem to be a
      relevant problem during pregnancy. Proper skin care as well as appropriate
      treatment applied by obstetricians and/or dermatologists may help women to
      recover.

PMID- 30215466
TI  - Prophylactic Effects of Ephedrine, Ondansetron and Ringer on Hemodynamic Changes
      during Cesarean Section under Spinal Anesthesia - a randomized clinical trial.
AB  - BACKGROUND: Hemodynamic change during spinal anaesthesia for cesarean section is
      prevalent. OBJECTIVE: Comparing the prophylactic effects of ephedrine,
      ondansetron and ringer on hemodynamic changes in patients undergoing cesarean
      section with spinal anaesthesia. MATERIAL AND METHODS: This randomized clinical
      trial was carried out on pregnant women undergoing elective cesarean sec-tion
      referred to teaching hospitals of Mashhad, Iran. Patients allocated to three
      groups of intravenous ondansetron (O) (4 mg, 5 min),intramuscular ephedrine (E)
      (25 mg, 25 min) and ringer (R) (500 ml, 20 min) prior to spinal anaesthesia.
      Anaesthesia inducted with 10-15 mg of bupivacaine. Vital signs were recorded
      every 3 minutes for 18 minutes including systolic blood pressure (SBP), diastolic
      blood pressure (DBP), mean arterial pressure (MAP), pulse rate (PR), pulse
      oximetry (SpO2). RESULTS: Ninety patients with a mean age of 29.4 +/- 5.4 years
      were studied in three groups of O (n = 30), E (n = 30), R (n = 30). Results
      showed a statistically significant difference in the incidence rate of
      hypotension 12 minutes after spinal anaesthesia in the three groups, but no
      statistically significant difference was found in the rest of minutes among the
      three groups. Dur-ing follow-up minutes, bradycardia was observed in only one
      patient (1.1%) of Group O and no cases of this sign were observed in other
      minutes and other groups. CONCLUSION: Intramuscular administration of ephedrine
      25 minutes prior to the spinal anaesthesia leads to better prevention of systolic
      blood pressure changes compared with intravenous ondansetron and ringer, while
      administration of ondansetron and ringer had the same effects on reducing
      hemodynamic changes.

PMID- 30215467
TI  - A review of randomized trials comparisons of epidural with parenteral forms of
      pain relief during labour and its impact on operative and cesarean delivery rate.
AB  - OBJECTIVES: The aim of this review was to summarise the available literature on
      different modalities of labour pain relief (epidural vs. parenteral) and to
      assess their impact on the rate of caesarean section deliveries and instrumental
      deliveries, and on the need to support the uterine contractile function. MATERIAL
      AND METHODS: The PubMed, Web of Science and Cochrane databases were reviewed to
      identify articles describing the effect of labour pain relief on the course of
      labour. This review includes 16 studies with 7150 patients. RESULTS: The analysis
      of the obtained data revealed that epidural analgesia (EA) or combined epidural
      and spinal anaesthesia (CESA) provided significantly better labour pain relief
      when compared with parenteral opioids. Conduction anaesthesia was not associated
      with an increase in the caesarean section delivery rate. Some authors concluded
      that conduction anaesthesia was associated with the need for assisted delivery.
      CONCLUSIONS: Epidural analgesia is a well-recognised method of labour pain
      relief. It is associated with the parturient's higher satisfaction when compared
      to parenteral opioids. EA does not directly increase the caesarean section
      delivery rate, yet it can lead to instrumental deliveries (vacuum-assisted,
      obstetrics forceps) and a need to pharmacologically support the uterine
      contractile function. Further studies are required to evaluate the effect of EA
      on the course of labour, and methods of minimising its adverse effects.

PMID- 30215468
TI  - Towards a hepatitis-free Egypt: is this achievable?

PMID- 30215469
TI  - Payment system of urban family physician programme in the Islamic Republic of
      Iran: is it appropriate?
AB  - Background: The payment system is pivotal in implementing policies in the health
      sector. Equitable access to healthcare is the main principle of the payment
      system. Aims: This study aimed to investigate aspects of the payment system in
      the urban family physician programme (FPP) in the Islamic Republic of Iran.
      Methods: This was a qualitative study. We obtained data from key informants and
      both formal and grey literature. We used content analysis for data analysis.
      Results: A range of concepts was explored related to the payment system of the
      FPP. By merging similar expressions, we categorized the findings into four main
      themes including: payment method, payment criteria and incentives, payment
      process and amount of payment. Conclusions: FPP is required to follow convenient
      implementation methods. The mechanisms of payment in the health sector are weak
      and have no transparency. A blurred combination of criteria makes an unclear
      process for determining the payment mechanisms. It is recommended that the
      opinions of key stakeholders be taken into consideration prior to developing
      payment mechanisms and financial incentives.

PMID- 30215470
TI  - Association between coronary artery disease and hepatitis C virus seropositivity.
AB  - Background: Coronary artery disease (CAD) is one of the leading causes of death
      worldwide. Predisposing factors include some infectious aetiologies that have a
      systemic effect like hepatitis C virus. Aims: The aim of this study was to
      explore the association between hepatitis C viral infection and coronary artery
      disease. Methods: This case-control study was designed to include 100 patients
      attending the Cardiology Department in Tanta University Hospital, Gharbia
      Governorate, Egypt, for diagnostic angiography. A consecutive sample of 50
      patients with abnormal angiographic findings was matched with another 50
      consecutive patients with normal angiographic findings regarding age, sex, and
      major risk factors for coronary artery disease (diabetes mellitus, hypertension
      and smoking). Patients were investigated for hepatitis C virus (HCV) infection.
      Results: We found that 46% of abnormal angiography were HCV-positive compared to
      28% of patients with normal angiography; this difference was not statistically
      significant. On studying the number of vessels affected among patients with
      abnormal angiography it was noted that one vessel affection was found mainly
      among HCV-negative patients (59.3% compared to 17.4% among HCV-negative and 
      positive patients). Multi-vessel affection was found mainly among HCV-positive
      patient (47.8% compared to 22.2% among HCV-positive and -negative respectively).
      Conclusions: The possible association between HCV positivity and extension of
      coronary artery disease may refer to the role of HCV in coronary artery disease
      pathology. Further studies on a large scale to investigate this association are
      recommended.

PMID- 30215471
TI  - Social, psychological and demographic variables related to breastfeeding among
      Kuwaiti mothers.
AB  - Background: Many studies have discussed the relationship between breastfeeding
      and certain social, psychological and demographic variables. Aims: The aim of
      this study was to determine the effect of social, psychological and demographic
      variables on breastfeeding among Kuwaiti mothers. Methods: The total of 712
      married women were selected who answered a questionnaire. Questions were asked
      about duration of breastfeeding and bottle feeding, degree of spousal
      relationship, religious sect and background. Religiosity, family stability and
      general health self-rating scales were used. Results: Women who came from urban
      roots and consanguineous marriages had a higher mean duration of breastfeeding
      than those who came from Bedouin roots and nonconsanguineous marriages. There was
      a significant difference among the three maternal age groups in the duration of
      breastfeeding. A significant relationship was found between the duration of
      breastfeeding and all social, psychological and demographic variables except
      general health. Correlations were found between the duration of breastfeeding and
      maternal and paternal education, maternal occupation, years of marriage, age at
      marriage, family stability scale, self-esteem scale, and socioeconomic variables.
      The duration of artificial feeding, number of abortions, degree of religiosity,
      family stability scale, age, and socioeconomic scale related to the duration of
      the mother's breastfeeding. Conclusions: Education plays an important role in
      affecting women's health in general and breastfeeding practice in particular.

PMID- 30215472
TI  - Associations between red reflex abnormality, consanguinity and intensive care
      hospitalization of newborns in Turkey.
AB  - Background: Red reflex screening is the primary but unheeded test for the
      detection of vision- and life-threatening eye conditions. Aims: To evaluate the
      red reflex of newborns, percentage of ocular diseases resulting in red reflex
      abnormality, and their relation with consanguinity in Southeast Turkey. Methods:
      Newborns (n = 1358) were examined with pencil light and direct ophthalmoscopy.
      Results: Eight hundred of these newborns were hospitalized in a rooming-in unit.
      (RIU) and 558 were in the neonatal intensive care service (NICS). In the RIU
      there were 7 (0.88%) newborns with abnormal red reflex and in the NICS there were
      14 (2.51%). Sensitivity of pencil light examination was 71.4%. Studies from the
      Middle East have shown potential recessive genetic causes of common paediatric
      ocular conditions. In our study, consanguineous marriage was found to have a
      significant association with red reflex abnormality (P = 0.017). Conclusions: Red
      reflex screening test is important in the early diagnosis of vision- and life
      threatening eye disorders in Southeast Turkey where consanguinity is common.

PMID- 30215473
TI  - Women's sexual and reproductive health care needs assessment: an Iranian
      perspective.
AB  - Background: Reproductive health problems are a leading cause of women's ill
      health and mortality worldwide. There is a need to investigate sexual and
      reproductive health care needs in different societies and cultural contexts.
      Despite the success in health care promotion in the Iranian health care system,
      women still need to receive sexual health care and appropriate HIV/AIDS services.
      However, studies on the sexual and reproductive health care needs of Iranian
      women are lacking. Aims: This study aimed to investigate the sexual and
      reproductive health care needs of women referred to health care centres in an
      urban area of the Islamic Republic of Iran. Methods: We carried out a cross
      sectional study in 2013 on 514 women living in an urban area in the north of the
      Islamic Republic of Iran. Taking into consideration ethical principles, data were
      collected using the Sexual and Reproductive Health Care Needs Assessment
      Questionnaire. Results: The findings showed a greater need for the provision of
      care by practitioners in the sexual history and activities domain (73%) compared
      with other domains. Also, the woman's age and the location where she sought
      treatment and care for sexually transmitted infections were predictors of sexual
      activities needs. Conclusions: Owing to the high prevalence of women's referral
      to health care centres seeking treatment of sexual disorders, there is a need for
      the provision of sexual counseling centres and services promoting women's
      reproductive health care.

PMID- 30215474
TI  - Use of induced abortion for birth control by mothers in Iraq.
AB  - Background: Induced abortion is a traditional method of birth control and it can
      indicate unmet maternal reproductive needs. Little is known about the use of
      induced abortion by married women in Iraq. Aims: This cross-sectional study aimed
      to explore whether induced abortion is used for birth control by married women in
      Mosul, and to determine the sociodemographic and family characteristics
      associated with its use. Methods: Multistage stratified sampling was used to
      recruit 1302 married women of child-bearing age (15-49 years) attending primary
      health care centres in Mosul. Women were interviewed using a validated
      questionnaire between April 2011 and 31 January 2012. Data collected included:
      use of induced abortion and method, social and family background, and
      contraceptive use. The chi2-test was used to assess the association of
      sociodemographic and cultural factors with the induced abortion. Results: Of the
      1302 women, 13.5% had tried to induce an abortion at some time, by undertaking
      heavy physical activities (66.2%) or using of herbal remedies (22.2%) or
      pharmacological preparations (17.6%). The prevalence of reported induced abortion
      was significantly lower among women using contraceptives, older women, those with
      a higher education, working women, suburban and rural residents, those living in
      extended families, and women in consanguineous marriages and non-polygynous
      marriages (P < 0.05). Conclusions: Over 10% of the married women had induced
      abortion to control births. Health education is recommended to encourage
      contraceptive use.

PMID- 30215475
TI  - Fruit and vegetable intake among Emirati adolescents: a mixed methods study.
AB  - Background: Interventions to promote healthy eating in adolescents are needed in
      the United Arab Emirates. To design effective interventions, adolescent eating
      behaviours need to be understood. Aims: This study aimed to describe eating
      behaviours of adolescents in Dubai and the factors associated with fruit and
      vegetable intake. Methods: This was a sequential explanatory study using a mixed
      methods approach. Ten of the 34 Arabic high schools in Dubai were randomly
      selected and students in grades 10-12 were included. Data were collected on self
      reported fruit and vegetables intake, eating behaviours, food availability and
      sociodemographic variables. In the qualitative phase, 14 students were
      interviewed about their eating behaviour. Results: A total of 620 students were
      included: 57% were boys and most reported medium/high family affluence. Only 28%
      of the participants met the recommended daily fruit and vegetable intake, with
      significantly more males than females meeting it (P < 0.01). Lunch was the most
      frequently eaten meal, breakfast was frequently skipped, and there were high
      levels of fast food and soft drink consumption. Adequate fruit and vegetable
      intake was positively associated with increased lunch frequency, being male,
      parental support for healthy eating, and positive perception of family meals.
      Conclusions: There are significant differences in eating habits between Emirati
      male and female adolescents. Lunch, as the main family meal, faces threats
      because of modern working hours. The gender-specific social context may require
      targeted interventions to achieve optimal outcomes in each group.

PMID- 30215476
TI  - Geographical inequality in cataract surgery among Iranians between 2006 and 2011.
AB  - Background: Cataract surgery is a highly cost-effective intervention for sight
      restoration but inequalities exist in its use which health care systems should
      aim to reduce. Aims: This study aimed to measure the level of inequality in
      cataract surgery use and the changes in inequality between 2006 and 2011 in the
      Islamic Republic of Iran. Methods: A number of metrics, including ranges and
      indexes based on Lorenz curves (Gini, concentration and dissimilarity indexes),
      were used to measure the inequality in cataract surgery use among Iranians in
      2006 and 2011. Cataract surgical numbers and socioeconomic data were obtained
      from a province-based survey and the national census database. Results:
      Significant inter-provincial and inter-regional differences were found in
      cataract surgical proportions. South Khorasan province had the lowest cataract
      surgical rate in 2006 and 2011, while Tehran province had the highest rate in
      both years. Inequality in the distribution of cataract surgery services decreased
      between 2006 and 2011: the Gini, concentration and dissimilarity indexes
      decreased by 0.028, 0.03 and 0.037, respectively. However, cataract surgery
      delivery remained in favour of the better-off provinces. Conclusions: To reduce
      this inequality, policy-makers should improve financial and physical access to
      cataract surgery, especially in the relatively deprived provinces, and tackle
      physician-induced demand.

PMID- 30215477
TI  - Engagement of health research institutions in knowledge translation in the
      Eastern Mediterranean Region.
AB  - Background: Health research institutions in the Eastern Mediterranean Region
      (EMR) can play an integral role in promoting and supporting Knowledge Translation
      (KT). Assessing institutions' engagement in KT and bridging the "research-
      policy" gap is important in designing context-specific strategies to promote KT
      and informing funding efforts in the region. Aims: The objective of this study
      was to explore the engagement of EMR institutions in KT activities. Methods: A
      cross-sectional survey of institutions undertaking health research in the 22 EMR
      countries was undertaken. The survey covered institutional characteristics,
      institutional planning for research, national planning for health research, and
      knowledge management, translation and dissemination. Results: 575 institutions
      were contacted of which 223 (38.3%) responded. Half the sampled institutions
      reported conducting priority-setting exercises, with 60.2% not following a
      standardized approach. Less than half institutions reported frequently/ always
      (40.5%) involving policymakers and stakeholders in setting priorities for
      research on health. Only 26.5% of respondent institutions reported that they
      examine the extent to which health policymakers utilize their research results.
      Moreover, only 23.3% reported measuring the impact of their health research.
      Conclusions: There is still misalignment between national health research
      priorities and actual research production, and KT activities are still rarely
      undertaken by institutions in the EMR. National governments and international
      funding agencies are called to support research production and translation in the
      EMR. Institutions and researchers are also called to produce policy-relevant
      research and be responsive to the needs and priorities of policy-makers.

PMID- 30215478
TI  - Health challenges and access to health care among Syrian refugees in Jordan: a
      review.
AB  - Background: Syrian refugees in Jordan are currently facing difficulties in
      accessing adequate healthcare. Aims: This study looked at the health conditions
      and barriers to accessing healthcare in Syrian refugees settled in Jordan.
      Methods: Pubmed, CINAHL and Google Scholar were searched for published cross
      sectional studies on the health status of Syrian refugees, specifically the
      prevalence of chronic diseases, communicable diseases, physical impairments,
      emotional and mental health problems, and barriers to health care. The terms
      searched were: Syrian refugee, health access barriers, health access, chronic
      diseases, communicable diseases/infectious diseases, physical impairment and
      mental health. The prevalence and 95% confidence intervals (CI) were calculated.
      Results: The literature search yielded 265 articles, of which 8 were eligible for
      inclusion. The prevalence of the conditions assessed were: chronic diseases, 29%
      (95% CI: 0.190-0.429); communicable diseases, 42.9% (95% CI: 0.184-0.713);
      emotional and mental health problems, 32.9% (95% CI: 0.191-0.504); physical
      impairment, 14.4% (95% CI: 0.056-0.322). Financial issues were the greatest
      barrier to accessing health care for 66% (95% CI: 0.449-0.823%). Conclusions: The
      health challenges of Syrian refugees are not just about chronic and acute
      diseases, injuries, or shortage of health resources or health disparities. It is
      a health burden that has become an economic, political and social crisis for the
      Jordanian government and its people, and measures and support to help Jordan
      continue to provide for refugees are needed.

PMID- 30215479
TI  - Cancer care for adolescents and young adults in Jordan.
AB  - Background: Adolescents and young adults with cancer have special characteristics
      and needs. Aims: This study highlighted psychosocial challenges, fertility issues
      and secondary diseases encountered in adolescents and young adults with cancer.
      This work is meant to be a platform for future interventions for cancer in this
      demographic. Methods: We investigated the latest edition of the Jordan Cancer
      Registry (JCR) and our more comprehensive institutional database during 2000
      2012. Smoking, obesity and fertility preservation were addressed briefly as
      important issues among AYA patients. Results: Cancer among adolescents and young
      adults represents 16.3% of all new cancer cases and has increased by 25% over the
      past 12 years. Women are more likely to be involved (female: male ratio of 1.44:
      1) because of thyroid and breast cancers. Five-year survival rate for the AYA
      group was 72.4%, which was significantly better than for adults aged >= 40 years
      (59.8%) but worse than for paediatric patients aged < 15 years (79.2%) (P <
      0.0001). Conclusions: Cancer in adolescents and young adults represents a
      substantial and growing proportion of oncological diagnoses. Due to their special
      needs and treatment complications, a dedicated service is urgently needed.

PMID- 30215481
TI  - Twenty-third meeting of the Eastern Mediterranean Regional Working Group on GAVI,
      the Vaccine Alliance.

PMID- 30215480
TI  - Reducing maternal mortality: the case for availability and safety of blood
      supply.

PMID- 30215482
TI  - Using the framework approach to analyse qualitative data: a worked example.
AB  - BACKGROUND: Data management and analysis are crucial stages in research,
      particularly qualitative research, which accumulates large volumes of data. There
      are various approaches that can be used to manage and analyse qualitative data,
      the framework approach being one example widely used in nursing research. AIMS:
      To consider the strengths and challenges of the framework approach and its
      application to practice. To help the novice researcher select an approach to
      thematic analysis. DISCUSSION: This paper provides an account of one novice
      researcher's experience of using the framework approach for thematic analysis. It
      begins with an explanation of the approach and why it was selected, followed by
      its application to practice using a worked example, and an account of the
      strengths and challenges of using this approach. CONCLUSION: The framework
      approach offers the researcher a systematic structure to manage, analyse and
      identify themes, enabling the development and maintenance of a transparent audit
      trail. It is particularly useful with large volumes of text and is suitable for
      use with different qualitative approaches.

PMID- 30215483
TI  - [Research of magnesium alloys and plga degradated in vivo and micro-ct evaluate
      the degradation of magnesium].

PMID- 30215484
TI  - [Antibacterial study on human umbilical cord mesenchymal stem cells supernatant
      combined with amoxicillin on Staphylococcus aureus].

PMID- 30215485
TI  - [Advances in total femur replacement].
AB  - Objective: To summarize the advances of total femur replacement in recent years.
      Methods: The literature related to total femur replacement was reviewed, and the
      indications, techniques, prosthesis design, complications, rehabilitation, and
      function were summarized. Results: The indication of total femur replacement is a
      wide involvement of the femur, skip lesions and a huge bone defect in revision.
      Watson-Jone is the main incision in the proximal, and then the full length of the
      thigh to the patella. Vascular and nerve bundle, abduction muscles are well
      protected, and combined or costumed prosthesis are replaced. The prosthesis
      design progresses, showing a diversified prostheses. Complication is frequent and
      varied. Rehabilitation in early stage is physical therapy, weight training is
      evolutionary. The main function evaluation system is Musculoskeletal Tumor
      Society (MSTS) score. Conclusion: Total femur replacement is effective in limb
      salvage. Large sample size and long-term follow-up study should be carried out to
      unify indications and functional exercise standards and reduce postoperative
      complications.

PMID- 30215486
TI  - ?

PMID- 30215488
TI  - ?

PMID- 30215487
TI  - [The application and research progress of technology of in-situ tissue
      engineering in bone and cartilage tissue engineering].
AB  - Objective: To review the application and research progress of technology of in
      situ tissue engineering in bone and cartilage tissue engineering. Methods: The
      original articles about technology of in-situ tissue engineering in bone and
      cartilage tissue engineering were extensively reviewed and analyzed. Results: In
      situ tissue engineering have been shown to be effective in repairing bone defects
      and cartilage defects, but biological mechanisms are inadequate. At present, most
      of researches are mainly focused on animal experiments, and the effect of
      clinical repair need further study. Conclusion: Technology of in-situ tissue
      engineering has wide application prospects in bone and cartilage tissue
      engineering. However, further study on the mechanism of related cytokines need to
      be conducted.

PMID- 30215489
TI  - [Research progress of knee-salvage treatment for knee osteoarthritis].
AB  - Objective: To review the progress of knee-salvage treatment based on the step
      therapy idea for knee osteoarthritis (KOA). Methods: The domestic and foreign
      literature in recent years was searched, and the treatments of KOA at different
      stages were summarized and analyzed. Results: The treatment of KOA is aimed at
      alleviating symptoms, delaying structural changes of joints, maintaining joint
      function, and improving quality of life. So the conservative treatment is still
      the first choice for KOA at early stage. Arthroscopic surgery can assist in the
      diagnosis and classification, simultaneously remove the intra-articular
      irritants, and limitedly repair the cartilage. Osteotomy is suitable for the KOA
      with abnormal lower extremity weight bearing line and articular line. And it can
      effectively balance the weight bearing stress of knee joint, improve the clinical
      symptom, and alleviate the progression of disease. Joint distraction can improve
      the mechanical environment of knee joint and repair the defect cartilage partly.
      With the technical development, unicompartmental knee arthroplasty (UKA) is back
      in fashion in recent years. It is a kind of real joint surface replacement, which
      is an important means of knee preservation method in patients with anterior
      medial KOA. Conclusion: At present, there are many knee-salvage treatments based
      on the severity of the disease. Osteotomy and UKA are the most widely used and
      successful surgical techniques for knee preservation. However, the indications
      should be properly selected, and the surgeon should accumulate enough clinical
      experience. Otherwise, it is difficult to achieve good results.

PMID- 30215490
TI  - [The treatment of Tillaux bone block in the Ruedi-Allgower type III Pilon
      fractures].
AB  - Objective: To analyze the importance and effectiveness of Tillaux bone block in
      Ruedi-Allgower type III of Pilon fracture surgery. Method: Twenty-one patients
      with Pilon fractures with Tillaux dislocation were treated between February 2010
      and September 2013. There were 17 males and 4 females, aged from 28 to 68 years
      with an average age of 42.9 years. The causes of injury included falling from
      height in 13 cases, falls injury in 4 cases, crush injury in 2 cases, and
      sprained injury in 2 cases. X-ray films and CT examination showed that all 21
      patients had fibula fracture and Tillaux block had obvious displacement.
      According to AO/OTA classification, there were 3 cases of C1.2, 1 case of C1.3,
      10 cases of C2, and 7 cases of C3. The duration of injury to preoperative period
      ranged from 4 to 31 days, with an average of 10 days. All cases of Pilon fracture
      were treated with open reduction plate internal fixation. Select steel plate or
      screw to fixation for Tillaux block; allograft bone graft was selected for
      compression of fracture. Results: There were 2 cases of skin necrosis at the
      corner of wound after operation, and the wound healed after corresponding
      treatment; the wound healed at first intention in the other 19 cases. The effect
      of surgical reduction was evaluated by Burwell-Chamley imaging scoring system
      within 72 hours after operation, there were 19 cases of anatomical reduction and
      2 cases of general reduction. All the 21 patients were followed up 18 to 48
      months, with an average of 24.9 months. No complications such as nerve injury,
      loosening of internal fixation, and periprosthetic fracture were found during
      follow-up. All fractures obtained bone healing, which lasted from 4 to 8 months,
      with an average of 6 months. The ankle and hindfoot scores of the American
      Orthopaedic Foot and Ankle Society (AOFAS) were used to evaluate the ankle and
      hindfoot function at 1 year after operation or at last follow-up, the results
      were excellent in 13 cases, good in 6 cases, and fair in 2 cases, with an
      excellent and good rate of 90.5%. Internal fixator was removed from 19 patients
      at 15-19 months after operation. There were 17 cases of joint hyperplasia and 4
      cases of osteoarthritis. All joint mobility was restored. The functional recovery
      of the ankle joint was evaluated according to the Olerud-Molander ankle fracture
      score standard, the results were good in 6 cases, fair in 8 cases, and poor in 7
      cases at postoperative full weight training; and after 1 year of full weight
      training, the results were excellent in 10 cases, good in 3 cases, fair in 6
      cases, and poor in 2 cases. Conclusion: The Tillaux bone block is a reliable
      marker for the restoration of complex Pilon fractures. The reconstruction of the
      Tillaux can be used as a marker to improve the effectiveness of complex Pilon
      fractures.

PMID- 30215492
TI  - ?

PMID- 30215491
TI  - [Suture-bridge fixation under arthroscopy in treatment of tibial eminence
      avulsion fracture of anterior cruciate ligament in adolescents].
AB  - Objective: To explore effectiveness of suture-bridge fixation under arthroscopy
      in treatment of tibial eminence avulsion fracture of anterior cruciate ligament
      in adolescents. Methods: Between June 2013 and October 2016, 18 adolescent
      patients suffered tibial eminence avulsion fracture of anterior cruciate ligament
      were treated by suture-bridge fixation under arthroscopy. There were 11 males and
      7 females with an average age of 12.5 years (range, 5-17 years). The injury
      caused by bruise in 6 cases, by sprain in 4 cases, and by sport injury in 8
      cases. The interval between injury and admission ranged from 2 hours to 10 months
      (mean, 2 months). The results of preoperative Lachman and anterior drawer tests
      were positive. There were 10 cases of knee pain, 4 cases of knee extension
      limitation, and 4 cases of knee extension without strength. According to the
      Meyer-McKeever classification criteria, 12 cases were type II and 6 cases were
      type III. Results: All incisions healed by first intention. All 18 patients were
      followed up 10-18 months after operation, with an average of 12 months.
      Postoperative X-ray films showed that all fractures healed after 6-12 weeks
      (mean, 8 weeks). The results of postoperative Lachman and anterior drawer tests
      were negative. At last follow-up, the Lysholm knee score was 90.1+/-5.0 and
      93.1+/-6.2 for affected and unaffected sides, respectively, showing no
      significant difference between affected and unaffected sides( t=0.669,
      P=3.184[?]). There was no premature closure of skeleton or leg length discrepancy
      and deformity. Conclusion: For tibial eminence avulsion fracture of anterior
      cruciate ligament in adolescents, the suture-bridge fixation under arthroscopy is
      an effective method with many advantages, such as minimal invasion, reliable
      fixation, good fracture healing, and no need for second operation to remove
      implants.

PMID- 30215493
TI  - [Progress of total ankle arthroplasty for end-stage ankle osteoarthritis].
AB  - Objective: To review the progress of total ankle arthroplasty (TAA) in treatment
      of end-stage ankle osteoarthritis (AOA). Methods: The literature about TAA at
      home and abroad in recent years were reviewed. The current status and progress of
      TAA were summarized from the results of traditional and computer-assisted TAA
      clinical outcomes. Results: End-stage AOA often leads to severe pain and
      dysfunction, and arthrodesis is still the main selective option. In recent years,
      with the advancement of surgical techniques and prosthesis design, TAA which can
      remain joint mobility has increased gradually, and the surgical results also have
      significant progress. Accurate prosthesis implant and mechanical alignment
      restoration are critical factors for TAA, and surgery-related malalignment is
      quite essential for the prosthesis survive. Computer assisted patient-specific
      guide can simplify the TAA procedures and obtain the accuracy of tibia and talus
      osteotomy. Conclusion: The clinical efficiency of preoperative CT based patient
      specific guide technology for TAA needs further clinical follow-up. Meanwhile, it
      is necessary to further develop intraoperative navigation and robotic surgery
      system suitable for TAA.

PMID- 30215494
TI  - [Effectiveness comparison of open reduction and internal fixation for open and
      closed ankle Logsplitter fractures].
AB  - Objective: To investigate the effectiveness of open reduction and internal
      fixation on high-energy ankle Logsplitter injuries (a kind of transsyndesmotic
      ankle fracture dislocation), and compare the prognosis between open and closed
      Logsplitter fracture. Methods: The clinical data of 36 Logsplitter fractures
      treated with open reduction and internal fixation between April 2011 and May 2016
      were retrospectively analyzed. Among them, 15 cases were open fracture and
      dislocation (open group) and 21 cases were closed fracture and dislocation
      (closed group). There was no significant difference between the two groups in
      gender, age, combined injury, injury to hospital admission time, and other
      general data ( P>0.05), with comparability. The wound healing, ankle mobility
      recovery, complications, and fracture healing were observed after operation. The
      ankle function was evaluated by the American Orthopaedic Foot and Ankle Society
      (AOFAS) score. Results: Both groups were followed up 12-29 months (mean, 19
      months). There was no significant difference in the follow-up time between the
      open group and the closed group ( t=1.169, P=0.251). In the open group, there
      were 3 cases of postoperative infection, 3 cases of nonunion, and 5 cases of post
      traumatic osteoarthritis; the above complications occurred in 1 case in the
      closed group; there was no significant difference in complications between the
      two groups ( P=0.41) except post-traumatic osteoarthritis ( P=0.02). At last
      follow-up, there was no significant difference in AOFAS score between the two
      groups ( t=1.981, P=0.056). According to AOFAS score criterion, the results were
      good in 10 cases and general in 5 cases in the open group, and good in 13 cases
      and general in 8 cases in the closed group, showing no significant difference (
      P=0.45). There was no significant difference in the fracture healing time and
      ankle flexion, dorsal extension, varus, and valgus motion between the two groups
      ( P>0.05). Conclusion: Open reduction and internal fixation for open or closed
      Logsplitter fractures can achieve satisfactory results, improve fracture healing
      rate, effectively reduce the incidence of complications, and improve ankle
      function.

PMID- 30215495
TI  - [Editorial Office of Chinese Journal of Reparative and Reconstructive Surgery].
AB  - Objective: To summarize the effectiveness of delayed skin-stretching device in
      treatment of skin and soft tissue defects. Methods: Between December 2014 and
      December 2016, 10 cases of skin and soft tissue defects were treated with delayed
      skin-stretching device. There were 6 males and 4 females with an average age of
      53 years (range, 42-64 years). The skin and soft tissue defects were caused by
      acute trauma in 6 cases. The incision could not be closed directly after making
      incisions because of osseous fascia syndrome in 3 cases. The skin soft tissue
      defect caused after huge carbuncle incision and drainage in 1 case. The defect
      located at thigh in 4 cases, lower leg in 3 cases, upper arm in 2 cases, back in
      1 case. The defect area ranged from 10 cm*4 cm to 22 cm*12 cm. Pinch test was
      performed on the wound margin, which confirmed that the wound could not be closed
      directly. Results: Tension blisters were found in 3 cases during traction, and no
      complications such as impaired blood circulation or skin necrosis occurred in all
      cases. Skin defects closed directly after continuously stretching for 7-18 days.
      No skin graft or free flap repair was performed in all patients. The wound healed
      well after operation. All the 10 patients were followed up 5-8 months (mean, 6.5
      months). There was no necrosis around the wound margin and the scar was linear.
      The sensation and function were not affected. Conclusion: Delayed skin-stretching
      device is an effective method to treat skin and soft tissue defects, which has
      the advantages of simple operation, lower risk of operation, less complications,
      and reliable effectiveness.

PMID- 30215496
TI  - [Effectiveness comparison between the paratricipital approach and the chevron
      olecranon V osteotomy approach in the treatment of type C3 distal humeral
      fractures].
AB  - Objective: To compare the effectiveness between paratricipital approach and
      chevron olecranon V osteotomy approach for the treatment of type C3 (AO/OTA)
      distal humeral fractures and investigate the details of operation. Methods:
      Between April 2010 and September 2016, 36 type C3 (AO/OTA) distal humeral
      fractures were treated with open reduction and bicolumnar orthogonal locking
      plating fixation by paratricipital approach and chevron olecranon V osteotomy
      approach respectively. The patients were divided into 2 groups by approach, there
      were 17 cases in paratricipital group (group A) and the bicolumns and distal
      humeral joint surface were exposed by traction of triceps and olecranon, and the
      distal humeral joint surface of the 19 cases in chevron olecranon V osteotomy
      group (group B) were exposed by osteotomy of the olecranon and reversing of
      triceps. There was no significant difference in gender, age, dominant side,
      interval between injury and surgery, causes of injury between 2 groups ( P>0.05).
      Patients were followed up, the postoperative range of motion of elbow joint,
      strength, pain, and stability in 2 groups were documented and compared; the elbow
      joint function was evaluated according to Mayo elbow performance score (MEPS).
      Results: The operation time of group A [(115.0+/-10.4) minutes] was less than
      that of group B [(121.0+/-12.3) minutes], but there was no significant difference
      ( t=-1.580, P=0.123). All patients in 2 groups got over 1 year follow-up and
      there was no significant difference of the follow-up time between 2 groups ( t=
      0.843, P=0.405). There was 1 case of heterotopic ossification in each group; 1
      case of incision infection in group A and 1 case of incision superficial
      infection in group B, and were cured after 2 weeks of intravenous antibiotics
      administration. There was no other operative complications in the 2 groups. At 3
      months after operation, all the distal humerus healed. At last follow-up, the
      elbow flexion extension range of groups A and B were (102.0+/-12.6) degrees  and
      (99.5+/-10.1) degrees  respectively, showing no significant difference ( t=
      0.681, P=0.501). The MEPS scores of groups A and B were 82.9+/-7.3 and 81.3+/-7.2
      respectively, showing no significant difference ( t=0.670, P=0.507); and the
      evaluation grade also showed no significant difference between 2 groups ( Z=
      0.442, P=0.659). Conclusion: By paratricipital approach and proper traction of
      the olecranon, the distal humeral articular surface can be exposed in the
      operation of type C3 distal humeral fractures, followed with same stable fixation
      after reduction, the effectiveness is equal to by chevron olecranon V osteotomy
      approach.

PMID- 30215497
TI  - Treatment of rigid congenital clubfoot with Ilizarov technique in older children
AB  - Objective: To investigate the effectiveness of Ilizarov technique in treatment of
      rigid congenital clubfoot in older children. Methods: A clinical data of 55
      patients (69 feet) with rigid congenital clubfoot (Dimeglio grade IV) between
      September 2005 and September 2015 were retrospectively analyzed. There were 33
      boys and 22 girls with an average age of 11 years (range, 6-14 years). There were
      41 cases of unilateral clubfoot and 14 cases of bilateral clubfeet. The degree of
      foot deformity was rated as fair in 24 feet and as poor in 45 feet according to
      International Clubfoot Study Group (ICFSG) score before operation. Sixty-nine
      feet were treated by Ilizarov external fixator combined with limited soft tissue
      release, and 21 feet were combined with individualized V-shaped osteotomies.
      Results: All patients were followed up 2-10 years ( mean, 4.2 years). The
      incisions healed well after operation. Five cases of needle tract infection
      occurred and were cured by local dressing change. The effectiveness was excellent
      in 39 feet, good in 21 feet, and fair in 9 feet according to ICFSG score, with
      the excellent and good rate of 87.0%. During the follow-up, X-ray films showed
      that no blood supply disorder or necrosis of talus, scaphoid, cuneiform,
      metatarsal, calcaneus, and cuboid occurred. No osteomyelitis occurred.
      Conclusion: Ilizarov technique combined with limited soft tissue release or V
      shaped osteotomy for the older children with rigid congenital clubfeet is safe
      and can obtain significant orthopedic effectiveness.

PMID- 30215498
TI  - Research progress of knee-salvage treatment for knee osteoarthritis
AB  - Objective: To review the progress of knee-salvage treatment based on the step
      therapy idea for knee osteoarthritis (KOA). Methods: The domestic and foreign
      literature in recent years was searched, and the treatments of KOA at different
      stages were summarized and analyzed. Results: The treatment of KOA is aimed at
      alleviating symptoms, delaying structural changes of joints, maintaining joint
      function, and improving quality of life. So the conservative treatment is still
      the first choice for KOA at early stage. Arthroscopic surgery can assist in the
      diagnosis and classification, simultaneously remove the intra-articular
      irritants, and limitedly repair the cartilage. Osteotomy is suitable for the KOA
      with abnormal lower extremity weight bearing line and articular line. And it can
      effectively balance the weight bearing stress of knee joint, improve the clinical
      symptom, and alleviate the progression of disease. Joint distraction can improve
      the mechanical environment of knee joint and repair the defect cartilage partly.
      With the technical development, unicompartmental knee arthroplasty (UKA) is back
      in fashion in recent years. It is a kind of real joint surface replacement, which
      is an important means of knee preservation method in patients with anterior
      medial KOA. Conclusion: At present, there are many knee-salvage treatments based
      on the severity of the disease. Osteotomy and UKA are the most widely used and
      successful surgical techniques for knee preservation. However, the indications
      should be properly selected, and the surgeon should accumulate enough clinical
      experience. Otherwise, it is difficult to achieve good results.

PMID- 30215499
TI  - Ilizarov technique for treatment of distal radius deformity and bone defect after
      trauma
AB  - Objective: To investigate the effectiveness on the distal radius deformity and
      bone defect after trauma by using Ilizarov external fixator. Methods: The
      clinical data of 9 patients of post-traumatic distal radius deformity with bone
      defect treated by Ilizarov technique between January 2012 and December 2016 were
      retrospectively analyzed. There were 7 males and 2 females with an average age of
      25.6 years (range, 11-46 years). Of the 9 cases, 4 were radial baseball hand
      deformity with large bone defect, 4 were short deformity of distal radius, 1 was
      distal radius deformity with radial deflection and pronation deformity, all with
      distal dislocation of the distant radial-ulnar joint. The time from injury to
      operation was 6 months to 6.2 years (mean, 1.5 years). The bone defect was 1.4
      6.8 cm (mean, 3.6 cm). After complete debridement, the forearm was fixed with
      Ilizarov external fixator. At 7 days after operation, bone transport or bone
      lengthening was performed at the rate of 0.8-1 mm/d, 4 times a day, the deformity
      was slowly corrected and the bone defect was repaired. According to the loss of
      palmar tilt angle and ulnar tilt angle measured before operation, the position of
      distal radial articular surface was gradually adjusted in the course of moving or
      prolonging, so as to restore palmar tilt angle and ulnar tilt angle as far as
      possible. Results: All wounds healed by first intention and no leakage or rupture
      occurred. All the 9 patients were followed up 15-36 months (mean, 23 months). All
      the radius defects healed and the distal deformity was corrected, the healing
      time was 92.4-138.6 days (mean, 104.7 days); the external fixation index was 32.6
      51.1 days/cm (mean, 40.2 days/cm). After 2 months of external fixator removal,
      the wrist joint flexion was (42.6+/-3.1) degrees , the wrist dorsum extension was
      (48.5+/-4.7) degrees , the palm inclination angle was (11.5+/-1.3) degrees , and
      the ulnar deviation angle was (21.2+/-3.7) degrees ; the elbow flexion was
      (128.2+/-6.4) degrees , the elbow extension was (3.2+/-2.1) degrees , the forearm
      pronation was (71.5+/-4.3) degrees , and the forearm rotation was (38.2+/-6.5)
      degrees ; the wrist and elbow joint extension and forearm rotation were
      significantly improved when compared with preoperative values ( P<0.05). At last
      follow-up, wrist function was assessed according to Gartland-Werley standard, the
      results were excellent in 3 cases, good in 5 cases, and fair in 1 case. Four
      cases had pinhole infection, and were cured after anti inflammatory dressing
      change or replacement of needles; 3 cases did not heal at the bone junction, and
      were healed after bone grafting; 4 cases deviated from the radial force line, and
      the deformity was corrected after adjusting the needle. Conclusion: Ilizarov
      technique can correct deformity and reconstruct bone defect of the post-traumatic
      distal radius simultaneously, so it is a good method to treat this kind of
      disease.

PMID- 30215500
TI  - [Effectiveness of tibio-talo-calcaneal arthrodesis with full thread headless
      compression screws via combined minimal incisions].
AB  - Objective: To investigate the effectiveness of tibio-talo-calcaneal arthrodesis
      with full thread headless compression screws via combined minimal incisions.
      Methods: Between January 2012 and December 2016, 36 patients (36 feet) with ankle
      diseases underwent tibio-talo-calcaneal arthrodesis with parallel double thread
      headless compression screws via minimal anterior and lateral oblique incisions.
      There were 14 males and 22 females with an average age of 53.8 years (range, 18
      76 years). There were 19 cases of left feet and 17 cases of right feet. There
      were 21 cases of talar necrosis, 7 cases of post-traumatic arthritis, 3 cases of
      rheumatoid arthritis, 2 cases of tuberculosis infection (inactive), 1 case of
      talar absence, 1 case of Charcot's disease, and 1 case of pigmented villonodular
      synovitis of ankle and subtalar joints. Preoperative American Orthopaedic Foot
      and Ankle Society (AOFAS) score and visual analogue scale (VAS) score were 53.7+/
      2.5 and 5.9+/-0.2, respectively. The operation time was recorded and the wound
      healing and complications were observed. The bone healing was assessed by X-ray
      film and CT scanning. The function and pain of joint were evaluated by AOFAS and
      VAS scores. Results: The mean operation time was 49.8 minutes (range, 33-82
      minutes). Incision infection occurred in 1 patient (2.8%) at 3 weeks after
      operation, and recovered after debridement. The other incisions healed by first
      intention without complications. Thirty-five patients were followed up with an
      average of 18.5 months (range, 12-29 months). Imaging examination showed fusion
      of the ankle and subtalar joints with an average fusion time of 10.9 weeks
      (range, 8-15 weeks). After 1 year, the AOFAS score (84.7+/-0.6) and VAS score
      (0.3+/-0.1) were significantly higher than preoperative scores ( t=12.596,
      P=0.000; t=30.393, P=0.000). Conclusion: It is an effective surgical method of
      tibio-talo-calcaneal arthrodesis with full thread headless compression screws via
      combined minimal incisions for end-stage ankle disease because of the less
      complications incidence and the higher postoperative fusion rate.

PMID- 30215501
TI  - Sprayed, Scalable, Wearable, and Portable NO2 Sensor Array Using Fully Flexible
      AgNPs-All-Carbon Nanostructures.
AB  - Flexible chemical sensors usually require transfer of prepared layers or whole
      device onto special flexible substrates and further attachment to target objects,
      limiting the practical applications. Herein, a sprayed gas sensor array utilizing
      silver nanoparticles (AgNPs)-all-carbon hybrid nanostructures is introduced to
      enable direct device preparation on various target objects. The fully flexible
      device is formed using metallic single-walled carbon nanotubes as conductive
      electrodes and AgNPs-decorated reduced graphene oxide as sensing layers. The
      sensor presents sensitive response ( Ra/ Rg) of 6.0-20 ppm NO2, great mechanical
      robustness (3000 bending cycles), and obvious sensing ability as low as 0.2 ppm
      NO2 at room temperature. The sensitivity is about 3.3 and 13 times as that of the
      sample based on metal electrodes and the sample without AgNP decoration. The
      fabrication method demonstrates good scalability and suitability on the planar
      and nonplanar supports. The devices attached on a lab coat or the human body
      perform stable performance, indicating practicability in wearable and portable
      fields. The flexible and scalable sensor provides a new choice for real-time
      monitoring of toxic gases in personal mobile electronics and human-machine
      interactions.

PMID- 30215502
TI  - Effect of Silicon Surface for Perovskite/Silicon Tandem Solar Cells: Flat or
      Textured?
AB  - Perovskite and textured silicon solar cells were integrated into a tandem solar
      cell through a stacking method. To consider the effective structure of silicon
      solar cells for perovskite/silicon tandem solar cells, the optic and photovoltaic
      properties of textured and flat silicon surfaces were compared using mechanical
      stacking-tandem of two- and four-terminal structures by perovskite layers on
      crystal silicon wafers. The reflectance of the texture silicon surface in the
      range of 750-1050 nm could be reduced more than that of the flat silicon surface
      (from 2.7 to 0.8%), which resulted in increases in average incident photon to
      current conversion efficiency values (from 83.0 to 88.0%) and current density
      (from 13.7 to 14.8 mA/cm2). Using the texture surface of silicon heterojunction
      (SHJ) solar cells, the significant conversion efficiency of 21.4% was achieved by
      four-terminal device, which was an increase of 2.4% from that of SHJ solar cells
      alone.

PMID- 30215503
TI  - Leeches-Inspired Hydrogel-Elastomer Integration Materials.
AB  - Inspired by the functions of leeches, for the first time homogeneous materials
      integrating hydrogels and elastomers were achieved by free radical
      polymerization. 2-Methoxyethyl acrylate (MEA) was used as elastomer monomer and
      Pluronics functionalized with vinyl groups acted as cross-linkers to impart the
      hydrogel property to the materials. The resulting Pluronic/PMEA gels possess a
      swelling ratio of about 210% and good water-retaining ability. Compression tests
      of Pluronic/PMEA gels at swelling equilibrium state show a stress up to 1.6 MPa
      under 85% strain. The gels act as elastomer after dehydration. Uniaxial tensile
      fracture stress and the elongation reached 1200 kPa and 500%, respectively, and
      compression stress was above 22 MPa. Furthermore, the Pluronic/PMEA gels also
      show self-healing properties. Owing to the excellent mechanical performance in
      both wet and dry conditions, this hydrogel-elastomer integrated material may have
      potential applications in tissue engineering, soft robotics, and biomedical
      devices.

PMID- 30215504
TI  - Achieving a High-Performance Carbon Anode through the P-O Bond for Lithium-Ion
      Batteries.
AB  - Carbon materials with high initial Coulombic efficiency (ICE) and specific
      capacity in lithium-ion batteries are highly attractive. Herein, P-doped carbon
      has been prepared, and as an anode for lithium-ion batteries, it exhibits
      remarkably improved ICE and reversible capacity. P atoms are apt for the
      formation of the P-O bond in carbon with oxygen-containing groups. The doped P
      content strongly depends on the O content in carbon. The high-doped P content of
      5.79 at. % can be obtained through changing the O content in carbon. Carbon with
      high contents of P and O displays high ICE and capacity as an anode for lithium
      ion batteries. The P-O bond in carbon changes the morphology and composition of
      the solid electrolyte interface (SEI) layer and is beneficial to the formation of
      a thin and dense SEI layer. The P-O bond in carbon prevents the permeation and
      decomposition of solvated PF6- in the interior of the electrode during cycling,
      resulting in the improved ICE, reversible capacity, and rate capability. As an
      anode for lithium-ion batteries, the ICE can be improved to 70.9% for carbon with
      the P-O bond from 36.9% for carbon without the P-O bond. Carbon with the P-O bond
      displays high specific capacities of 566 mA h g-1 after 100 cycles at 0.1 A g-1
      and 432 mA h g-1 after 1000 cycles at 1 A g-1. This design offers a simple and
      efficient method to improve the ICE and reversible capacity of hard carbon.

PMID- 30215505
TI  - Dual-Color Fluorescent Timer Enables Detection of Growth-Arrested Pathogenic
      Bacterium.
AB  - We present a method capable of detecting single slow-growing and growth-arrested
      cells in a bacterial culture composed of physiologically and phenotypically
      different cells. Unlike the use of transcriptional reporters to gauge the
      metabolic activities in cells, here, we fuse two different fluorescent proteins
      with distinctive maturation rates to construct a timer to directly determine the
      growth rate of single Pseudomonas aeruginosa cells. We demonstrate that the dual
      color fluorescent timer can indicate the slow-growing and growth-arrested cells
      from bacterial cultures in the presence of various environmental stresses,
      including nutrient starvation or antibiotic treatments, which greatly expand the
      methods for detecting and isolating persister cells.

PMID- 30215506
TI  - Laser-Induced Carbon-Based Smart Flexible Sensor Array for Multiflavors
      Detection.
AB  - We report a flexible sensor array electronic tongue system that is fabricated on
      a polymer substrate by the laser direct writing process for multiflavor
      detection. Electronic tongue is a sensing system that is applied to detect
      different elements with the same sensor array. By analyzing responses from
      different measurement units, it enables a cross-sensitivity, namely, the ability
      of the system to responding to a range of different analytes in solution without
      specific functionalization of sensors. In this article, a six-unit sensing array
      system was fabricated by a laser direct writing process. Sensing units were
      introduced on a flexible polyamide surface. A high surface-volume ratio porous
      carbon structure was created by a laser-induced carbonization process, which
      provides stable conductive carbon electrodes with high sensitivity. Different
      surface treatments, such as gold plating, reduced-graphene oxide coating, and
      polyaniline coating, were accomplished for different measurement units. By
      applying principal component analysis, this sensing system shows a promising
      result for the detection of multiple flavors. The detection limit for each
      element is about 0.1 mM for NaCl and sugar solutions. Also, it is able to detect
      10-4 times diluted commercial table vinegar solution, which originally contains
      5% acetic acid. The detection limit is theoretically lower than the human
      threshold of 10 mM for NaCl and sugar. Besides, the sensing system shows a high
      sensitivity and selectivity for mixed elements. By mapping the data points, the
      sensor system could detect flavor combinations and provide a reliable prediction
      of analyte concentration ratios.

PMID- 30215507
TI  - Correlative Microscopy in 3D: Helium Ion Microscopy-Based Photogrammetric
      Topography Reconstruction Combined with in situ Secondary Ion Mass Spectrometry.
AB  - The chemical or elemental analysis of samples with complex surface topography is
      challenging for secondary ion mass spectrometry (SIMS), if the three-dimensional
      structure of the sample is not taken into account. Conventional 3D reconstruction
      of SIMS data assumes a flat surface and uniform sputtering conditions, which is
      not the case for many analytical applications involving micro- and nanosized
      particles, composites, or patterned materials. Reliable analysis of such samples
      requires knowledge of the actual 3D surface structure to correctly reconstruct
      the SIMS 3D maps. To this end, we introduce the use of photogrammetric 3D
      topography reconstruction from scanning helium ion microscopy (HIM) correlated
      with in situ SIMS data for the reconstruction of 3D SIMS data. The HIM and SIMS
      data are acquired under in situ conditions in a Zeiss ORION NanoFab HIM using a
      novel SIMS analyzer. We successfully tested the applicability of the approach to
      generate 3D models of different samples and show that the combination of SIMS and
      3D topography is able to provide insights into the influence of the sample
      topography in a single instrument and with a single ion column and hence without
      the need for ex-situ sample analysis or additional instrumentation. These
      findings offer a path toward ion-based correlative 3D spectromicroscopy (3D-HIM
      SIMS) and suggest that many combinations of charged particle based P3D (SEM, HIM)
      and analytical microscopy techniques, such as SIMS, energy-dispersive X-ray
      spectroscopy (EDX), or ionoluminescence/cathodoluminescence (IL/CL), can be used
      for correlative microscopy in 3D.

PMID- 30215508
TI  - Lactose-Modified Chitosan Gold(III)-PEGylated Complex-Bioconjugates: From
      Synthesis to Interaction with Targeted Galectin-1 Protein.
AB  - Galectins (Gal) are a family of glycan-binding proteins characterized by their
      affinity for beta-galactosides. Galectin-1 (Gal-1), a dimeric lectin with two
      galactoside-binding sites, regulates cancer progression and immune responses.
      Coordination chemistry has been engaged to develop versatile multivalent
      neoglycoconjugates for binding Gal-1. In this study we report a fast and original
      method to synthesize hybrid gold nanoparticles in which a hydrochloride lactose
      modified chitosan, named CTL, is mixed with dicarboxylic acid-terminated
      polyethylene glycol (PEG), leading to shell-like hybrid polymer-sugar-metal
      nanoparticles (CTL-PEG-AuNPs). The aim of this paper is to preliminarily study
      the interaction of the CTL-PEG-AuNPs with a target protein, namely, Gal-1, under
      specific conditions. The molecular interaction has been measured by Transmission
      Electron Microscopy (TEM), UV-vis, and Raman Spectroscopy on a large range of Gal
      1 concentrations (from 0 to 10-12 M). We observed that the interaction was
      strongly dependent on the Gal-1 concentration at the surface of the gold
      nanoparticles.

PMID- 30215509
TI  - Comparison of CCS Values Determined by Traveling Wave Ion Mobility Mass
      Spectrometry and Drift Tube Ion Mobility Mass Spectrometry.
AB  - Collision cross section (CCS, Omega) values determined by ion mobility mass
      spectrometry (IM-MS) provide the study of ion shape in the gas phase and use of
      these as further identification criteria in analytical approaches. Databases of
      CCS values for a variety of molecules determined by different instrument types
      are available. In this study, the comparability of CCS values determined by a
      drift tube ion mobility mass spectrometer (DTIM-MS) and a traveling wave ion
      mobility mass spectrometer (TWIM-MS) was investigated to test if a common
      database could be used across IM techniques. A total of 124 substances were
      measured with both systems and CCS values of [M + H]+ and [M + Na]+ adducts were
      compared. Deviations <1% were found for most substances, but some compounds show
      deviations up to 6.2%, which indicate that CCS databases cannot be used without
      care independently from the instrument type. Additionally, it was found that for
      several molecules [2M + Na]+ ions were formed during electrospray ionization,
      whereas a part of them disintegrates to [M + Na]+ ions after passing through the
      drift tube and before reaching the TOF region, resulting in two signals in their
      drift spectrum for the [M + Na]+ adduct. Finally, the impact of different LC-IM
      MS settings (solvent composition, solvent flow rate, desolvation temperature, and
      desolvation gas flow rate) were investigated to test whether they have an
      influence on the CCS values or not. The results showed that these conditions have
      no significant impact. Only for karbutilate changes in the drift spectrum could
      be observed with different solvent types and flow rates using the DTIM-MS system,
      which could be caused by the protonation at different sites in the molecule.

PMID- 30215510
TI  - Complementary Molecular and Elemental Mass-Spectrometric Imaging of Human Brain
      Tumors Resected by Fluorescence-Guided Surgery.
AB  - Fluorescence-guided surgery (FGS) has been established as a powerful technique
      for glioblastoma resection. After oral application of the prodrug 5
      aminolevulinic acid (5-ALA), protoporphyrin IX (PpIX) is formed as an
      intermediate of the heme-biosynthesis cascade and accumulates within the tumor.
      By intraoperative fluorescence microscopy, the specific PpIX fluorescence can be
      used to differentiate the tumor from healthy brain tissue. To investigate
      possible limitations of fluorescence diagnosis, the complementary use of
      molecular and elemental mass-spectrometry imaging (MSI) is presented. Matrix
      assisted laser-desorption-ionization mass spectrometry (MALDI-MS) is used to
      examine the distribution of PpIX and heme b in human brain tumors. MALDI-MS/MS
      imaging is performed to validate MS data and improve the signal-to-noise ratio
      (S/N). Comparing the imaging results with histological evaluation, increased PpIX
      accumulation in areas of high tumor-cell density is observed. Heme b accumulation
      are only found in areas of blood vessels and hemorrhage, confirming the hampered
      transformation from PpIX to heme b in glioblastoma tissue. Investigation of non
      neoplastic brain tissue and glioblastoma resected without external 5-ALA
      administration as control samples with true-negative fluorescence verified the
      absence of PpIX accumulation. Analysis of necrotic tumor tissue and gliosarcoma,
      one rare type of glioma appearing nonfluorescent during FGS, as case examples
      with false-negative-fluorescence diagnosis, revealed the absence of significant
      amounts of PpIX, indicating an impairment of PpIX formation. Molecular analysis
      is complemented by quantitative laser ablation-inductively coupled plasma (LA
      ICP) MSI correlating heme b and Fe distribution. Mathematical pixel-by-pixel
      correlation of molecular and elemental data revealed a positive correlation with
      heteroscedasticity for the spatially resolved heme b signal intensities and Fe
      concentrations.

PMID- 30215511
TI  - Interfacial Electron Beam Lithography: Chemical Monolayer Nanopatterning via
      Electron-Beam-Induced Interfacial Solid-Phase Oxidation.
AB  - Chemical nanopatterning-the deliberate nanoscale modification of the chemical
      nature of a solid surface-is conveniently realized using organic monolayer
      coatings to impart well-defined chemical functionalities to selected surface
      regions of the coated solid. Most monolayer patterning methods, however, exploit
      destructive processes that introduce topographic as well as other undesired
      structural and chemical transformations along with the desired surface chemical
      modification. In particular in electron beam lithography (EBL), organic
      monolayers have been used mainly as ultrathin resists capable of improving the
      resolution of patterning via local deposition or removal of material. On the
      basis of the recent discovery of a class of radiation-induced interfacial
      chemical transformations confined to the contact surface between two solids, we
      have advanced a direct, nondestructive EBL approach to chemical nanopatterning
      interfacial electron beam lithography (IEBL)-demonstrated here by the e-beam
      induced local oxidation of the -CH3 surface moieties of a highly ordered self
      assembled n-alkylsilane monolayer to -COOH while fully preserving the monolayer
      structural integrity and molecular organization. In this conceptually different
      EBL process, the traditional resist is replaced by a thin film coating that acts
      as a site-activated reagent/catalyst in the chemical modification of the coated
      surface, here the top surface of the to-be-patterned monolayer. Structural and
      chemical transformations induced in the thin film coating and the underlying
      monolayer upon exposure to the electron beam were elucidated using a
      semiquantitative surface characterization methodology that combines multimode AFM
      imaging with postpatterning surface chemical modifications and quantitative micro
      FTIR measurements. IEBL offers attractive opportunities in chemical
      nanopatterning, for example, by enabling the application of the advanced EBL
      technology to the straightforward nanoscale functionalization of the simplest
      commonly used organosilane monolayers.

PMID- 30215512
TI  - MIEF1 Microprotein Regulates Mitochondrial Translation.
AB  - Recent technological advances led to the discovery of hundreds to thousands of
      peptides and small proteins (microproteins) encoded by small open reading frames
      (smORFs). Characterization of new microproteins demonstrates their role in
      fundamental biological processes and highlights the value in discovering and
      characterizing more microproteins. The elucidation of microprotein-protein
      interactions (MPIs) is useful for determining the biochemical and cellular roles
      of microproteins. In this study, we characterize the protein interaction partners
      of mitochondrial elongation factor 1 microprotein (MIEF1-MP) using a proximity
      labeling strategy that relies on APEX2. MIEF1-MP localizes to the mitochondrial
      matrix where it interacts with the mitochondrial ribosome (mitoribosome).
      Functional studies demonstrate that MIEF1-MP regulates mitochondrial translation
      via its binding to the mitoribosome. Loss of MIEF1-MP decreases the mitochondrial
      translation rate, while an elevated level of MIEF1-MP increases the translation
      rate. The identification of MIEF1-MP reveals a new gene involved in this process.

PMID- 30215513
TI  - Trimethylsilyl-Induced N-O Bond Cleavage in Nitrous Oxide-Derived
      Aminodiazotates.
AB  - The chemical activation of nitrous oxide (N2O) typically results in O-atom
      transfer and the extrusion of N2 gas. In contrast, reactions of N-trimethylsilyl
      (TMS)-substituted amides with N2O give inorganic or organic azides, with
      concomitant formation of silanols or siloxanes. N-TMS-substituted amides are also
      able to induce N-O bond cleavage in N2O-derived dialkylaminodiazotates,
      generating tetrazene salts. These results indicate the potential of silyl groups
      in devising transformations, in which N2O acts as an N-atom donor.

PMID- 30215514
TI  - 195Pt NMR and Molecular Dynamics Simulation Study of the Solvation of [PtCl6]2-
      in Water-Methanol and Water-Dimethoxyethane Binary Mixtures.
AB  - The experimental 195Pt NMR chemical shift, delta(195Pt), of the [PtCl6]2- anion
      dissolved in binary mixtures of water and a fully miscible organic solvent is
      extremely sensitive to the composition of the mixture at room temperature.
      Significantly nonlinear delta(195Pt) trends as a function of solvent composition
      are observed in mixtures of water-methanol, or ethylene glycol, 2-methoxyethanol,
      and 1,2-dimethoxyethane (DME). The extent of the deviation from linearity of the
      delta(195Pt) trend depends strongly on the nature of the organic component in
      these solutions, which broadly suggests preferential solvation of the [PtCl6]2-
      anion by the organic molecule. This simplistic interpretation is based on an
      accepted view pertaining to monovalent cations in similar binary solvent
      mixtures. To elucidate these phenomena in detail, classical molecular dynamics
      computer simulations were performed for [PtCl6]2- in water-methanol and water-DME
      mixtures using the anionic charge scaling approach to account for the effect of
      electronic dielectric screening. Our simulations suggest that the simplistic
      model of preferential solvation of [PtCl6]2- by the organic component as inferred
      from nonlinear delta(195Pt) trends is not entirely accurate, particularly for
      water-DME mixtures. The delta(195Pt) trend in these mixtures levels off for high
      DME mole fractions, which results from apparent preferential location of [PtCl6]2
      anions at the borders of water-rich regions or clusters within these inherently
      micro-heterogeneous mixtures. By contrast in water-methanol mixtures, apparently
      less pronounced mixed solvent micro-heterogeneity is found, suggesting the
      experimental delta(195Pt) trend is consistent with a more moderate preferential
      solvation of [PtCl6]2- anions. This finding underlines the important role of
      solvent-solvent interactions and micro-heterogeneity in determining the solvation
      environment of [PtCl6]2- anions in binary solvent mixtures, probed by highly
      sensitive 195Pt NMR. The notion that preferential solvation of [PtCl6]2- results
      primarily from competing ion-solvent interactions as generally assumed for
      monatomic ions, may not be appropriate in general.

PMID- 30215515
TI  - Small and Bright Lithium-Based Upconverting Nanoparticles.
AB  - In the context of light-mediated tumor treatment, the application of ultraviolet
      (UV) radiation can initiate drug release and photodynamic therapy. However, its
      limited penetration depth in tissues impedes the subcutaneous applicability of
      such radiation. On the contrary, near-infrared (NIR) light is not energetic
      enough to initiate secondary photochemical processes, but can pierce tissues at a
      significantly greater depth. Upconverting nanoparticles (UCNPs) unify the
      advantages of both extremes of the optical spectrum, they can be excited by NIR
      irradiation and emit UV light through the process of upconversion, effective NIR
      to-UV generation being attained with UCNPs as large as 100 nm. However, in
      anticipation of biomedical applications, the size of UCNPs must be greatly
      minimized to favor their cellular internalization; yet straightforward size
      reduction negatively affects the NIR-to-UV upconversion efficiency. Herein, we
      propose a two-step strategy to obtain small yet bright lithium-based UCNPs.
      First, we synthesized UCNPs as small as 5 nm by controlling the relative amount
      of coordinating ligands, namely oleylamine (OM) and oleic acid (OA). Although
      these UCNPs were chemically unstable, particle coarsening via an annealing
      process in the presence of fresh OA yielded structurally stable and highly
      monodisperse sub-10 nm crystals. Second, we grew a shell with controlled
      thickness on these stabilized cores of UCNPs, improving the NIR-to-UV
      upconversion by orders of magnitude. Particularly in the case of
      LiYbF4:Tm3+/LiYF4 UCNPs, their NIR-to-UV upconversion surpassed the gold standard
      90 nm-sized LiYF4:Tm3+, Yb3+ UCNPs. All in all, these UCNPs show great potential
      within the biomedical framework as they successfully combine the requirements of
      small size, deep tissue NIR penetration and bright UV emission.

PMID- 30215516
TI  - Mechanistic Insight into Asymmetric Hetero-Michael Addition of alpha,beta
      Unsaturated Carboxylic Acids Catalyzed by Multifunctional Thioureas.
AB  - Carboxylic acids and their corresponding carboxylate anions are generally
      utilized as Bronsted acids/bases and oxygen nucleophiles in organic synthesis.
      However, a few asymmetric reactions have used carboxylic acids as electrophiles.
      Although chiral thioureas bearing both arylboronic acid and tertiary amine were
      found to promote the aza-Michael addition of BnONH2 to alpha,beta-unsaturated
      carboxylic acids with moderate to good enantioselectivities, the reaction
      mechanism remains to be clarified. Detailed investigation of the reaction using
      spectroscopic analysis and kinetic studies identified tetrahedral borate
      complexes, comprising two carboxylate anions, as reaction intermediates. We
      realized a dramatic improvement in product enantioselectivity with the addition
      of 1 equiv of benzoic acid. In this aza-Michael reaction, the boronic acid not
      only activates the carboxylate ligand as a Lewis acid, together with the thiourea
      NH-protons, but also functions as a Bronsted base through a benzoyloxy anion to
      activate the nucleophile. Moreover, molecular sieves were found to play an
      important role in generating the ternary borate complexes, which were crucial for
      obtaining high enantioselectivity as demonstrated by DFT calculations. We also
      designed a new thiourea catalyst for the intramolecular oxa-Michael addition to
      suppress another catalytic pathway via a binary borate complex using steric
      hindrance between the catalyst and substrate. Finally, to demonstrate the
      synthetic versatility of both hetero-Michael additions, we used them to
      accomplish the asymmetric synthesis of key intermediates in pharmaceutically
      important molecules, including sitagliptin and alpha-tocopherol.

PMID- 30215517
TI  - Photothermally Active Reduced Graphene Oxide/Bacterial Nanocellulose Composites
      as Biofouling-Resistant Ultrafiltration Membranes.
AB  - Biofouling poses one of the most serious challenges to membrane technologies by
      severely decreasing water flux and driving up operational costs. Here, we
      introduce a novel anti-biofouling ultrafiltration membrane based on reduced
      graphene oxide (RGO) and bacterial nanocellulose (BNC), which incoporates GO
      flakes into BNC in situ during its growth. In contrast to previously reported GO
      based membranes for water treatment, the RGO/BNC membrane exhibited excellent
      aqueous stability under environmentally relevant pH conditions, vigorous
      mechanical agitation/sonication, and even high pressure. Importantly, due to its
      excellent photothermal property, under light illumination, the membrane exhibited
      effective bactericidal activity, obviating the need for any treatment of the
      feedwater or external energy. The novel design and in situ incorporation of the
      membranes developed in this study present a proof-of-concept for realizing new,
      highly efficient, and environmental-friendly anti-biofouling membranes for water
      purification.

PMID- 30215518
TI  - Enantioselective Formal [4+1] Cycloaddition of Diazoarylacetates and the
      Danishefsky's Diene: Stereoselective Synthesis of (-)-1,13-Herbertenediol.
AB  - Rodium chiral diene complex-catalyzed enantioselective cycloaddition of aryl
      alpha-diazoarylacetates and electron-enriched Danishefsky-type dienes afforded
      highly functionalized and optically enriched cyclopentenones in excellent yields
      (up to 97% yield) and with good to excellent enantioselectivities (60-92% ee). (
      )-1,13-Herbertenediol was successfully synthesized in an overall 25% yield
      employing the optically enriched cyclopentenone with an all-carbon quaternary
      center as the key intermediate.

PMID- 30215519
TI  - Surveying the Energy Landscapes of Abeta Fibril Polymorphism.
AB  - Many unrelated proteins and peptides have been found spontaneously to form
      amyloid fibers above a critical concentration. Even for a single sequence,
      however, the amyloid fold is not a single well-defined structure. Although the
      cross-beta hydrogen bonding pattern is common to all amyloids, all other aspects
      of amyloid fiber structures are sensitive to both the sequence of the aggregating
      peptides and the solvent conditions under which the aggregation occurs. Amyloid
      fibers are easy to identify and grossly characterize using microscopy, but their
      insolubility and aperiodicity along the dimensions transverse to the fiber axis
      have complicated detailed experimental structural characterization. In this
      paper, we explore the landscape of possibilities for amyloid protofilament
      structures that are made up of a single stack of peptides associated in a
      parallel in-register manner. We view this landscape as a two-dimensional version
      of the usual three-dimensional protein folding problem: the survey of the two
      dimensional folds of protein ribbons. Adopting this view leads to a practical
      method of predicting stable protofilament structures of arbitrary sequences. We
      apply this scheme to variants of Abeta, the amyloid forming peptide that is
      characteristically associated with Alzheimer's disease. Consistent with what is
      known from experiment, we find that Abeta protofibrils are polymorphic. To our
      surprise, however, the ribbon-folding landscape of Abeta turned out to be
      strikingly simple. We confirm that, at the level of the monomeric protofilament,
      the landscape for the Abeta sequence is reasonably well funneled toward
      structures that are similar to those that have been determined by experiment. The
      landscape has more distinct minima than does a typical globular protein landscape
      but fewer and deeper minima than the landscape of a randomly shuffled sequence
      having the same overall composition. It is tempting to consider the possibility
      that the significant degree of funneling of Abeta's ribbon-folding landscape has
      arisen as a result of natural selection. More likely, however, the intermediate
      complexity of Abeta's ribbon-folding landscape has come from the post facto
      selection of the Abeta sequence as an object of study by researchers because only
      by having a landscape with some degree of funneling can ordered aggregation of
      such a peptide occur at in vivo concentrations. In addition to predicting
      polymorph structures, we show that predicted solubilities of polymorphs correlate
      with experiment and with their elongation free energies computed by coarse
      grained molecular dynamics.

PMID- 30215520
TI  - Theory of Diffusion-Influenced Reaction Networks.
AB  - A formalism is developed to describe how diffusion alters the kinetics of coupled
      reversible association-dissociation reactions in the presence of conformational
      changes that can modify the reactivity. The major difficulty in constructing a
      general theory is that, even to the lowest order, diffusion can change the
      structure of the rate equations of chemical kinetics by introducing new reaction
      channels (i.e., modifies the kinetic scheme). Therefore, the right formalism must
      be found that allows the influence of diffusion to be described in a concise and
      elegant way for networks of arbitrary complexity. Our key result is a set of non
      Markovian rate equations involving stoichiometric matrices and net reaction rates
      (fluxes), in which these rates are coupled by a time-dependent pair association
      flux matrix, whose elements have a simple physical interpretation. Specifically,
      each element is the probability density that an isolated pair of reactants
      irreversibly associates at time t via one reaction channel on the condition that
      it started out with the dissociation products of another (or the same) channel.
      In the Markovian limit, the coupling of the chemical rates is described by
      committors (or splitting/capture probabilities). The committor is the probability
      that an isolated pair of reactants formed by dissociation at one site will
      irreversibly associate at another site rather than diffuse apart. We illustrate
      the use of our formalism by considering three reversible reaction schemes: (1)
      binding to a single site, (2) binding to two inequivalent sites, and (3) binding
      to a site whose reactivity fluctuates. In the first example, we recover the
      results published earlier, while in the second one we show that a new reaction
      channel appears, which directly connects the two bound states. The third example
      is particularly interesting because all species become coupled and an exchange
      type bimolecular reaction appears. In the Markovian limit, some of the diffusion
      modified rate constants that describe new transitions become negative, indicating
      that memory effects cannot be ignored.

PMID- 30215521
TI  - Correction to "A Comprehensive Scope of Peripheral and Axial Substituent Effect
      on the Spectroelectrochemistry of Boron Subphthalocyanines".

PMID- 30215522
TI  - Dynamics of Structural Elements of GB1 beta-Hairpin Revealed by Tryptophan
      Cysteine Contact Formation Experiments.
AB  - Quenching of the triplet state of tryptophan by close contact with cysteine
      provides a tool for measuring the rate of intramolecular contact formation, one
      of the most elementary events in the folding process, in peptides and proteins
      using only natural probes. Here we present a study performed on a stabilized
      mutant of the second beta-hairpin of the GB1 domain, where we combine steady
      state fluorescence, laser-induced temperature-jump, and contact formation
      measurements to unveil the role of elementary structural components on hairpin
      dynamics and overall stability. In particular, our methodology provides access to
      the conformational dynamics of both the folded and unfolded state of the hairpin
      under native conditions, revealing the presence of extremely slow dynamics on the
      microsecond time scale in the unfolded state and coexistence of structures with
      partial pairing of the tails in the folded state. Comparing model peptides that
      mimic the turn sequence, we found that both ion pairing and hydrogen bonding due
      to the threonine side chain contribute to the propensity of turn formation but
      not to the much slower dynamics of the hydrophobic core formation. Interestingly,
      the dynamics of the turn region in isolation are significantly faster than the
      dynamics measured for the unfolded state of the complete hairpin, suggesting that
      non-native hydrophobic contacts slow down the reconfiguration dynamics of the
      unfolded state. Overall, the information extracted from these experiments
      provides kinetic limits on interconversions among conformational populations,
      hence enabling a simplified multistate free-energy landscape for the GB1 hairpin
      to be drawn.

PMID- 30215523
TI  - Combined Force Ramp and Equilibrium High-Resolution Investigations Reveal
      Multipath Heterogeneous Unfolding of Protein G.
AB  - Over the past two decades, one of the standard models of protein folding has been
      the "two-state" model, in which a protein only resides in the folded or fully
      unfolded states with a single pathway between them. Recent advances in spatial
      and temporal resolution of biophysical measurements have revealed "beyond-two
      state" complexity in protein folding, even for small, single-domain proteins. In
      this work, we used high-resolution optical tweezers to investigate the
      folding/unfolding kinetics of the B1 domain of immunoglobulin-binding protein G
      (GB1), a well-studied model system. Experiments were performed for GB1 both in
      and out of equilibrium using force spectroscopy. When the force was gradually
      ramped, simple single-peak folding force distributions were observed, while
      multiple rupture peaks were seen in the unfolding force distributions, consistent
      with multiple force-dependent parallel unfolding pathways. Force-dependent
      folding and unfolding rate constants were directly determined by both force-jump
      and fixed-trap measurements. Monte Carlo modeling using these rate constants was
      in good agreement with the force ramp data. The unfolding rate constants
      exhibited two different behaviors at low vs high force. At high force, the
      unfolding rate constant increased with increasing force, as previously reported
      by high force, high pulling speed force ramp measurements. However, at low force,
      the situation reversed and the unfolding rate constant decreased with increasing
      force. Taken together, these data indicate that this small protein has multiple
      distinct pathways to the native state on the free energy landscape.

PMID- 30215524
TI  - Expanding the Dynamic Range of Fluorescence Assays through Single-Molecule
      Counting and Intensity Calibration.
AB  - Surface capture assays can measure fluorescently labeled analytes across a 1000
      fold concentration range and at the sub-nanomolar level, but many biological
      molecules exhibit 1,000,000-fold variations in abundance down to the femtomolar
      level. The goal of this work is to expand the dynamic range of fluorescence
      assays by using imaging to combine molecular counting with single-molecule
      calibration of ensemble intensities. We evaluate optical limits imposed by
      surface-captured fluorescent labels, compare performances of different
      fluorophore classes, and use detector acquisition parameters to span wide ranges
      of fluorescence irradiance. We find that the fluorescent protein phycoerythrin
      provides uniquely suitable properties with exceptionally intense and homogeneous
      single-fluorophore brightness that can overcome arbitrary spot detection
      threshold biases. Major limitations imposed by nonspecifically bound fluorophores
      were then overcome using rolling circle amplification to densely label cancer
      associated miRNA biomarkers, allowing accurate single-molecule detection and
      calibration across nearly 5 orders of magnitude of concentration with a detection
      limit of 29 fM. These imaging and molecular counting strategies can be widely
      applied to expand the limit of detection and dynamic range of a variety of
      surface fluorescence assays.

PMID- 30215525
TI  - Organocatalytic Modified Guareschi-Thorpe Type Regioselective Synthesis: A
      Unified Direct Access to 5,6,7,8-Tetrahydroquinolines and Other Alicyclic[ b]
      Fused Pyridines.
AB  - An unprecedented organocatalytic, regioselective, modified Guareschi-Thorpe type
      protocol toward the modular synthesis of 5,6,7,8-tetrahydroquinolines 22a-g and
      other alicyclic[ b]-fused pyridines 23-28 via the identification of Chitosan as a
      heterogeneous catalyst is reported. This novel strategy is operationally simple
      and showed a wide range of functional group tolerance and substrate
      compatibility. The proposed mechanistic pathway involves an imine-enamine cascade
      approach for the synthesis of structurally diverse alicyclic[ b]-fused pyridine
      heterocycles. The gram scale synthesis and identification of a new class of
      antifungal molecules 29-31 emphasize the practicality of this method.

PMID- 30215526
TI  - Tandem Copper-Catalyzed Conjugate Addition-Diastereoselective Protonation of ( E)
      alpha-Trialkylsilyl-beta-Alkyl(Aryl)-alpha,beta-Unsaturated Esters.
AB  - A tandem Cu(I)-catalyzed conjugate addition of Kharasch
      reagents/diastereoselective protonation of ( E)-alpha-trialkylsilyl-beta
      alkyl(aryl)-alpha,beta-unsaturated esters afforded the saturated products with
      d.r. values of >20:1 favoring the anti-diastereomer in modest to excellent
      isolated yields.

PMID- 30215527
TI  - N-Sulfonyl Bisimidazoline Ligands and Their Applications in Pd(II)-Catalyzed
      Asymmetric Addition toward alpha-Tertiary Amines.
AB  - A new class of chiral N-sulfonyl bisimidazoline (Bim) ligands have been designed,
      prepared, and applied in Pd(II)-catalyzed asymmetric addition of arylboronic
      acids to isatin-derived N-Boc ketimines. The combination of Pd(OCOCF3)2 and N
      tosyl Bim ligand shows high catalytic activity and excellent asymmetric
      induction, enabling asymmetric addition to offer alpha-tertiary amines with
      generally good to high yields and excellent enantioselectivity (up to 96% yield,
      96% ee). This asymmetric Pd(II) catalysis can tolerate air conditions, providing
      a practical and operationally simple protocol toward the construction of an
      enantioenriched alpha-tertiary stereocenter.

PMID- 30215528
TI  - Biomolecular Simulations of Halogen Bonds with a GROMOS Force Field.
AB  - Halogen bonds (XBs) are non-covalent interactions in which halogens (X), acting
      as electrophiles, interact with Lewis bases. XBs are able to mediate protein
      ligand recognition and therefore play an important role in rational drug design.
      In this context, the development of molecular modeling tools that can tackle XBs
      is paramount. XBs are predominantly explained by the existence of a positive
      region on the electrostatic potential of X named the sigma-hole. Typically, with
      molecular mechanics force fields, this region is modeled using a charged extra
      point (EP) linked to X along the R-X covalent bond axis. In this work, we
      developed the first EP-based strategy for GROMOS force fields (specifically
      GROMOS 54A7) using bacteriophage T4 lysozyme in complex with both iodobenzene and
      iodopentafluorobenzene as a prototype system. Several EP parametrization schemes
      were tested by adding a virtual interaction site to ligand topologies retrieved
      from the Automated Topology Builder (ATB) and Repository. Contrary to previous
      approaches using other force fields, our analysis is based on the capability of
      each parametrization scheme to sample XBs during MD simulations. Our results
      indicate that the implementation of an EP at a distance from iodine corresponding
      to Rmin provides a good qualitative description of XBs in MD simulations,
      supporting the compatibility of our approach with the GROMOS 54A7 force field.

PMID- 30215530
TI  - Multilobular dermoid cyst of the orbit.
AB  - Dermoid cysts are histologically defined as surface epithelium encapsulating an
      inner lumen. They are well described in the literature as discrete, single
      masses, either circumscribed or dumbbell-shaped, with or without a longstanding
      fistula. Chronic granulomatous inflammation is often a feature of dermoid cysts,
      contributing to local soft tissue and bony destruction. Isolated multicystic
      dermoids are not well described. We present a case of a multilobular dermoid
      characterized both radiographically and histopathologically. These findings may
      be attributed to repeated rupture and reformation of the dermoid cyst. When
      possible, our experience favours early excision of orbital dermoid cysts to
      minimize morbidity.

PMID- 30215529
TI  - Life-course Smoking Trajectories and Risk of Emphysema in Middle Age: The CARDIA
      Lung Study.

PMID- 30215531
TI  - Non-occlusive mesenteric ischaemia: CT findings, clinical outcomes and assessment
      of the diameter of the superior mesenteric artery: Don't forget the reperfusion
      process!

PMID- 30215532
TI  - Pre-emptive skin treatments to prevent skin toxicity caused by anti-EGFR
      antibody: the real-world evidence in Japan.
AB  - AIM: Clinically managing skin toxicity associated with anti-EGFR antibody usage
      to treat colorectal cancer improves quality of life for colorectal cancer
      patients. This study assesses trends of pre-emptive skin treatments and their
      impact on subsequent dermatologist visits in Japanese colorectal cancer patients.
      PATIENTS & METHODS: Pre-emptive treatment status and dermatologist visit data
      were investigated for 9461 colorectal cancer patients who experienced anti-EGFR
      antibody treatment. Data were collected from an electronic hospital-based claims
      database. RESULTS: Pre-emptive treatments increased around 2013. Furthermore,
      subsequent dermatologist visits decreased significantly among the pre-emptive
      treatment group (p < 0.05). CONCLUSION: Pre-emptive skin treatments seem to be
      related to reducing subsequent dermatologist visits by severe skin toxicity
      prevention and gained popularity in Japan.

PMID- 30215533
TI  - Synovial Mesenchymal Stem Cells Derived From the Cotyloid Fossa Synovium Have
      Higher Self-renewal and Differentiation Potential Than Those From the Paralabral
      Synovium in the Hip Joint.
AB  - BACKGROUND: Several studies have shown the relationship between poorer clinical
      outcomes of arthroscopic femoroacetabular impingement syndrome surgery and focal
      chondral defects or global chondromalacia/osteoarthritis. Although recent studies
      described good outcomes after the conjunctive application of synovial mesenchymal
      stem cells (MSCs), none demonstrated the application of synovial MSCs for
      cartilaginous hip injuries. PURPOSE: To compare the characteristics of MSCs
      derived from the paralabral synovium and the cotyloid fossa synovium and
      determine which is the better source. STUDY DESIGN: Controlled laboratory study.
      METHODS: Synovium was harvested from 2 locations of the hip-paralabral and
      cotyloid fossa-from 18 donors. The number of cells, colony-forming units,
      viability, and differentiation capacities of adipose, bone, and cartilage were
      collected and compared between groups. In addition, real-time polymerase chain
      reaction was used to assess the differentiation capacity of adipose, bone, and
      cartilage tissue from both samples. RESULTS: The number of colonies and yield
      obtained at passage 0 of synovium from the cotyloid fossa was significantly
      higher than that of the paralabral synovium ( P < .01). In adipogenesis
      experiments, the frequency of detecting oil red O-positive colonies was
      significantly higher in the cotyloid fossa than in the paralabral synovium ( P <
      .05). In osteogenesis experiments, the frequency of von Kossa and alkaline
      phosphatase positive colonies was higher in the cotyloid fossa synovium than in
      the paralabral synovium ( P < .05). In chondrogenic experiments, the chondrogenic
      pellet culture and the gene expressions of COL2a1 and SOX9 were higher in the
      cotyloid fossa synovium than in the paralabral synovium ( P < .05). CONCLUSION:
      MSCs from the cotyloid fossa synovium have higher proliferation and
      differentiation potential than do those from the paralabral synovium and are
      therefore a better source. CLINICAL RELEVANCE: Synovial cells from the cotyloid
      fossa synovium of patients with femoroacetabular impingement syndrome are more
      robust in vitro, suggesting that MSCs from this source may be strongly considered
      for stem cell therapy.

PMID- 30215535
TI  - Fair global drug pricing.

PMID- 30215534
TI  - The autophagy receptor SQSTM1/p62 mediates anti-inflammatory actions of the
      selective NR3C1/glucocorticoid receptor modulator compound A (CpdA) in
      macrophages.
AB  - Glucocorticoids are widely used to treat inflammatory disorders; however,
      prolonged use of glucocorticoids results in side effects including osteoporosis,
      diabetes and obesity. Compound A (CpdA), identified as a selective
      NR3C1/glucocorticoid receptor (nuclear receptor subfamily 3, group C, member 1)
      modulator, exhibits an inflammation-suppressive effect, largely in the absence of
      detrimental side effects. To understand the mechanistic differences between the
      classic glucocorticoid dexamethasone (DEX) and CpdA, we looked for proteins
      oppositely regulated in bone marrow-derived macrophages using an unbiased
      proteomics approach. We found that the autophagy receptor SQSTM1 but not NR3C1
      mediates the anti-inflammatory action of CpdA. CpdA drives SQSTM1 upregulation by
      recruiting the NFE2L2 transcription factor to its promoter. In contrast, the
      classic NR3C1 ligand dexamethasone recruits NR3C1 to the Sqstm1 promoter and
      other NFE2L2-controlled gene promoters, resulting in gene downregulation. Both
      DEX and CpdA induce autophagy, with marked different autophagy characteristics
      and morphology. Suppression of LPS-induced Il6 and Ccl2 genes by CpdA in
      macrophages is hampered upon Sqstm1 silencing, confirming that SQSTM1 is
      essential for the anti-inflammatory capacity of CpdA, at least in this cell type.
      Together, these results demonstrate how off-target mechanisms of selective NR3C1
      ligands may contribute to a more efficient anti-inflammatory therapy.

PMID- 30215536
TI  - An Overview on the Methods of Determining the Activity of Indoleamine 2, 3
      dioxygenase 1.
AB  - Immune escape plays an important hallmark of cancer. The tryptophan-catabolizing
      enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) is involved in the immune escape
      mechanism of human tumors, the expression of which is associated with a poor
      prognosis in cancer and correlated with tumor progression clinically. Therefore,
      finding the inhibitors targeting IDO1 may be an impellent approach that can
      reverse the complicated processes in tumor immune escape and induce an antitumor
      response as well. Here, we summarized and compared some methods of determining
      the activity of IDO1 and they can be used to screen IDO1 inhibitors as well,
      including HPLC, fluorescence detection, cell-based assay, NFK GreenScreenTM and
      absorbance assay. Each determining method possesses special advantages and
      disadvantages, so we need to have a comprehensive view of these methods and
      select the most suitable one for further research.

PMID- 30215537
TI  - Circular RNA hsa_circ_0000993 inhibits metastasis of gastric cancer cells.
AB  - AIM: We aimed to explore the roles of circRNAs in gastric cancer. MATERIALS &
      METHODS: The dysregulated circRNAs and miRNAs were identified using data from
      Gene Expression Omnibus. The roles of specifically selected circRNAs were
      explored. Survival analysis was performed using data from the Cancer Genome
      Atlas. RESULTS: We identified 68 dysregulated circRNAs and 51 dysregulated
      miRNAs. We found that hsa_circ_0000993 inhibited migration, invasion and
      proliferation of gastric cancer cells and could act as a miRNA sponge for miR-214
      5p but did not modulate expression of its parental gene, ATL2. Survival analysis
      showed that gastric cancer patients with lowly expressed miR-214-5p had a
      significantly better overall survival. CONCLUSION: In conclusion,
      hsa_circ_0000993 may inhibit metastasis of gastric cancer through sequestering
      miR-214-5p.

PMID- 30215539
TI  - Effect of diammonium glycyrrhizinate on pharmacokinetics of omeprazole by
      regulating cytochrome P450 enzymes and plasma protein binding rate.
AB  - 1. In clinical practice, diammonium glycyrrhizinate is usually used with
      omeprazole in patients with viral hepatitis and cirrhosis accompanied by peptic
      ulcers. However, the drug interaction between diammonium glycyrrhizinate and
      omeprazole remains unclear. 2. In this study, the effects of diammonium
      glycyrrhizinate on the pharmacokinetics of omeprazole was investigated by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analytical method. Male
      Sprague-Dawley rats were randomly assigned to two groups: omeprazole and
      omeprazole+diammonium glycyrrhizinate, and the main pharmacokinetic parameters
      were estimated after oral administration. It was found that using the omeprazole
      along with the diammonium glycyrrhizinate increased the AUC, AUMC, Cmax for
      omeprazole. 3. For this reason, we used the LC-MS/MS to detect the binding rate
      of plasma protein (BRPP) of omeprazole in rats, it was found that diammonium
      glycyrrhizinate could decrease the BRPP in rats. In addition, we found that
      diammonium glycyrrhizinate specifically inhibited the enzyme activity of the
      CYP2C19 and CYP3A4, which are involved in the metabolism of the omeprazole. 4.
      These results mean that diammonium glycyrrhizinate could inhibit the metabolism
      and increase the plasma concentration of the omeprazole in rats. Overall,
      diammonium glycyrrhizinate can influence the pharmacokinetics of omeprazole by
      inhibiting CYP2C19 and CYP3A4 activities and decreasing BRPP of omeprazole.

PMID- 30215538
TI  - Comparative Outcomes of Preoperative Chemoradiotherapy and Selective
      Postoperative Chemoradiotherapy in Clinical Stage T3N0 Low and Mid Rectal Cancer.
AB  - : Purpose/aim: Preoperative chemoradiotherapy (pre-CRT) and total mesorectal
      excision (TME) have become the standard of care for patients with locally
      advanced rectal cancer (LARC). Nevertheless, it is a controversial issue whether
      pre-CRT in cT3N0M0 patients would result in potential overtreatment. MATERIALS
      AND METHODS: In total, 183 clinical stage IIA rectal cancer patients treated with
      and without pre-CRT between 2011 and 2014 were retrospectively analyzed.
      Capecitabine/FOLFOX/CAPOX chemotherapy was co-administered with preoperative
      radiotherapy. Surgical resection with laparoscopic or open TME was conducted 8-12
      weeks after completion of the pre-CRT. Postoperative radiotherapy was routinely
      given to patients with pT4 lesion or circumferential margin (CRM) and/or distal
      resection margin (DRM) involvement. RESULTS: In total, 108 (59%) patients
      received pre-CRT and 75 (41%) underwent surgery first. The pre-CRT patients
      presented with less-advanced pathological T stage tumors compared with the
      surgery-first patients (p < 0.001). However, the pathological N stage was not
      significantly different between the two groups (p = 0.065). The 3-year overall
      survival (OS), disease-free survival (DFS), and 2-year local recurrence (LR) rate
      were similar in the pre-CRT and surgery-first patients (88.4 versus 88.7%, p =
      0.552; 79.6 versus 83.3%, p = 0.797; 2.8 versus 2.7%, p = 0.960, respectively).
      Cox regression analysis showed that pN stage and CRM/DRM involvement were
      independently correlated with an unfavorable DFS. CONCLUSIONS: In this study, the
      omission of pre-CRT in cT3N0M0 patients did not translate into a worse
      oncological outcome. Postoperative radiotherapy should remain a standard option
      for patients with CRM/DRM involvement and pathological T4 tumors. A generalized
      indication for pre-CRT in cT3N0 patients is likely to result in overtreatment.

PMID- 30215540
TI  - Development of a clinical decision rule for diagnosing sinus infections - to
      reduce unnecessary antibiotic prescribing.

PMID- 30215541
TI  - Selective brain cooling: Let us have a moment of science.
AB  - Selective brain cooling is a promising advent for reducing final infarct volume
      and improving outcomes in ischemic stroke victims. Despite the robust body of
      evidence from animal studies, evidence supporting the use of selective
      hypothermia in stroke patients is lacking. A recent study provided promising
      results on the safety and possible efficacy of selective brain hypothermia via
      intraarterial infusion of cooled saline. Better understanding of the patients'
      population that may attain benefit from this approach will be informative.
      Details of infarct progression using perfusion imaging will also help understand
      the mechanism of effect of selective hypothermia to inform future trials.

PMID- 30215543
TI  - Inhaled migraine drug therapy: a start of the art therapeutic strategy or just
      another gimmick?

PMID- 30215542
TI  - In vitro phase I metabolism of vinclozolin by human liver microsomes.
AB  - 1. Vinclozolin (Vin) is a fungicide used in agricultural settings and is
      classified as an endocrine disruptor. Vin is non-enzymatically hydrolyzed to 2
      [[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1) and 3',5'
      dichloro-2-hydroxy-2-methylbut-3-enanilide (M2) metabolites. There is no
      information about Vin biotransformation in humans, therefore, the aim of this
      study was to characterize its in vitro metabolism using human liver microsomes.
      2. Vin was metabolized to the [3-(3,5-dichlorophenyl)-5-methyl-5-(1,2
      dihydroxyethyl)-1,3-oxazolidine-2,4-dione] (M4) and N-(2,3,4-trihydroxy-2-methyl
      1-oxo)-3,5-dichlorophenyl-1-carbamic acid (M7) metabolites, which are unstable
      and gradually converted to 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutyranilide
      (DTMBA, formerly denoted as M5). M4 and DTMBA metabolites co-eluted in the same
      HPLC peak; this co-elute peak exhibited a Michaelis-Menten kinetic, whereas M7
      showed a substrate inhibition kinetics. The KM app for co-eluted M4/DTMBA and M7
      was 24.2+/-5.6 and 116.0+/-52.6 MUM, the VMax app was 0.280+/-0.015 and 0.180+/
      0.060 nmoles/min/mg protein, and the CLint app was 11.5 and 1.5 mL/min/g protein,
      respectively. The Ki for M7 was 133.2+/-63.9 MUM. Cytochrome P450 (CYP) chemical
      inhibitors furafylline (CYP1A2), ketoconazole (CYP3A4), pilocarpine (CYP2A6), and
      sulfaphenazole (CYP2C9) inhibited M4/DTMBA and M7 formation, suggesting that Vin
      is metabolized in humans by CYP. 3. DTMBA is a stable metabolite and specific of
      Vin, therefore it could be used as a biomarker of Vin exposure in humans to
      perform epidemiological studies.

PMID- 30215544
TI  - Changes in Throwing Arm Mechanics at Increased Throwing Distances During
      Structured Long-Toss.
AB  - BACKGROUND: Elbow injuries among adolescent baseball players have been outpacing
      those of college and professional players. In attempts to prevent injuries and
      maximize return-to-play potential following injury, attention has been focused on
      "return to throw" programs, which include long-toss throws. Because the few
      studies that were conducted on long-toss throwing focused primarily on college
      aged athletes, it is not known what type of load is incurred at the elbow during
      interval throwing progression among high school baseball players. PURPOSE: To
      quantify the change in arm slot, arm speed, shoulder external rotation, and elbow
      varus torque across increasing throwing distances within a given athlete. STUDY
      DESIGN: Descriptive laboratory study. METHODS: Ninety-five high school baseball
      players performed a long-toss protocol while wearing an inertial sensor and
      sleeve. Each participant was tested for 5 throws at distances of 9 m, 18 m, 27 m,
      37 m, and 46 m. Linear mixed-effects models and likelihood ratio tests were used
      to estimate the within-participant relationship between throw distance and arm
      slot, arm speed, shoulder external rotation, and elbow varus torque. RESULTS: Arm
      slot ( P < .01), arm speed ( P < .01), shoulder external rotation ( P < .01), and
      elbow varus torque ( P < .01) were significantly associated with long-toss throw
      distance. As the throw distance increased, there was an increase in arm speed and
      shoulder external rotation and a decrease in arm slot for each distance. However,
      elbow varus torque increased with each distance up to 37 m and then remained the
      same at 46 m. CONCLUSION: The use of longer distances for conditioning and
      rehabilitation may be beneficial in increasing shoulder range of motion and arm
      speed; however, precaution needs to be taken, as throwing longer distances are
      accompanied by an increase in arm rotation, arm speed, and elbow torque, with a
      decrease in arm slot. CLINICAL RELEVANCE: Return-to-throw programs have been
      utilized by sports medicine clinicians and coaches to help guide a player during
      rehabilitation. These programs involve throwing at increased efforts through
      increased distances with no immediate feedback on elbow stress. This
      investigation describes arm biomechanical changes during submaximum interval
      throwing and demonstrates a tool that can be utilized to measure arm stress in
      real time for clinicians and athletes progressing through an interval throwing
      program.

PMID- 30215545
TI  - 19F-NMR-based determination of the absorption, metabolism and excretion of the
      oral phosphatidylinositol-3-kinase (PI3K) delta inhibitor leniolisib (CDZ173) in
      healthy volunteers.
AB  - 1. Leniolisib is a novel oral phosphatidylinositol-3-kinase (PI3K) delta
      inhibitor, currently in clinical development for the treatment of inflammatory
      and autoimmune diseases. 2. We investigated the absorption, metabolism, and
      excretion of leniolisib in healthy subjects after a single oral 400 mg dose as
      part of a first-in-human clinical study. The parent drug and metabolites were
      quantified by 19F-NMR in plasma, urine and faeces after liquid chromatography
      separation, and structures were determined by liquid chromatography coupled to
      tandem mass spectrometry. 3. Drug-related material was mainly excreted as
      oxidative metabolites in urine and faeces, providing evidence that elimination
      occurs mainly by metabolism. No metabolites were abundant in plasma relative to
      the parent drug. An average mass balance of 66% was obtained, demonstrating that
      relatively extensive elimination/excretion data can be obtained by 19F-NMR in a
      first in human clinical study without the use of a radiolabeled drug.

PMID- 30215546
TI  - Pre-clinical imaging for establishment and comparison of orthotopic non-small
      cell lung carcinoma: in search for models reflecting clinical scenarios.
AB  - OBJECTIVE:: Clinically relevant animal models of non-small cell lung carcinoma
      (NSCLC) are required for the validation of novel treatments. We compared two
      different orthotopic transplantation techniques as well as imaging modalities to
      identify suitable mouse models mimicking clinical scenarios. METHODS:: We used
      three genomically diverse NSCLC cell lines [National Cancer Institute (NCI)-H1703
      adenosquamous cell carcinoma, NCI-H23 adenocarcinoma and A549 adenocarcinoma) for
      implanting tumour cells either as spheroids or cell suspension into lung
      parenchyma. Bioluminescence imaging (BLI) and contrast-enhanced cone beam CT
      (CBCT) were performed twice weekly to monitor tumour growth. Tumour histological
      data and microenvironmental parameters were determined. RESULTS:: Tumour
      development after spheroid-based transplantation differs probably due to the
      integrity of spheroids, as H1703 developed single localised nodules, whereas H23
      showed diffuse metastatic spread starting early after transplantation. A549
      transplantation as cell suspension with the help of a stereotactic system was
      associated with initial single localised tumour growth and eventual metastatic
      spread. Imaging techniques were successfully applied to monitor longitudinal
      tumour growth: BLI revealed highly sensitive qualitative data, whereas CBCT was
      associated with less sensitive quantitative data. Histology revealed significant
      model-dependent heterogeneity in proliferation, hypoxia, perfusion and necrosis.
      CONCLUSION:: Our developed orthotopic NSCLC tumours have similarity with
      biological growth behaviour comparable to that seen in the clinic and could
      therefore be used as attractive models to study tumour biology and evaluate new
      therapeutic strategies. The use of human cancer cell lines facilitates testing of
      different genomic tumour profiles that may affect treatment outcomes. ADVANCES IN
      KNOWLEDGE:: The combination of different imaging modalities to identify tumour
      growth with subsequent use in treatment planning and orthotopic transplantation
      techniques to develop initially single lesions to ultimate metastases pave the
      way towards representative pre-clinical NSCLC models for experimental testing of
      novel therapeutic options in future studies.

PMID- 30215547
TI  - LncRNA DUXAP10 modulates cell proliferation in esophageal squamous cell carcinoma
      through epigenetically silencing p21.
AB  - Esophageal Squamous Cell Carcinoma (ESCC) belongs to malignant tumor of human
      digestive system. It has greatly threatened human health both mentally and
      physically. Long non-coding RNAs have been discovered to be special molecular
      regulators in various cancers, including ESCC. LncRNA DUXAP10 is a newfound RNA,
      which is able to improve the progression of cancers 1-3 . In this study, DUXAP10
      was certified to be upregulated in ESCC tissues and cells. Besides, it was
      positively correlated with short survival time. Moreover, down-expression of
      DUXAP10 contributed to decreased cell proliferation and metastasis. Silenced
      DUXAP10 led to increased apoptosis rate and stagnation of cell cycle. Results of
      mechanism experiments suggested that DUXAP10 motivated ESCC progression through
      recruiting enhancer of zeste homolog 2 (EZH2) to the promoter of p21. Our
      findings suggested that the pseudogene-derived from lncRNA DUXAP10 drove the
      biological progression of ESCC. DUXAP10 was likely to be a potential therapeutic
      target for ESCC.

PMID- 30215548
TI  - Homocysteine Might Increase the Risk of Recurrence in Patients Presenting with
      Primary Cerebral Infarction.
AB  - PURPOSE: Although hyperhomocysteinemia (Hhcy) is a risk factor for cerebral
      infarction, its effect on recurrent cerebral infarction is less-defined. We aimed
      to investigate the association of Hhcy and increased risk of recurrent cerebral
      infarct. MATERIALS AND METHODS: From 2011-2013, we recruited 231 primary cerebral
      infarct patients that were divided to a Hhcy group (n = 105) and a control group
      (n = 126) according to plasma homocysteinemia (Hcy) levels exceeding 15MUmol/L.
      In this prospective study, risk factors like gender, age, blood lipid and glucose
      levels, history of diabetes, high blood pressure, smoking habits, and plasma Hhcy
      levels were determined. A three-year follow-up compared differences in cerebral
      infarction recurrence rates. Statistical analyses identified whether plasma Hhcy
      levels were an independent risk factor for recurrent cerebral infarction.
      RESULTS: Triglyceride and low density lipoprotein (LDL) levels in the Hhcy group
      were significantly higher than controls, and cerebral infarct recurrence rates in
      the Hhcy group exceeded control subject rates through the three-year follow-up (P
      = 0.021, P = 0.036, and P = 0.025). Cox proportional hazards modeling showed that
      elevated Hhcy levels (Hazard ratio [HR] = 3.062, P<0.001), increased age (HR =
      1.069, P<0.01), circulating triglyceride levels (HR = 1.686, P = 0.048), and
      relative National Institutes of Health Stroke (NIHSS) score (HR = 1.068, P =
      0.016) were risk factors for recurrent cerebral infarction. CONCLUSIONS: Level of
      Hhcy was a risk factor for recurrent cerebral infarction. Further, particular
      demographic and clinical outcomes including age, relative NIHSS scores, and
      circulating triglyceride levels were markedly associated with the occurrence of
      cerebral infarction.

PMID- 30215549
TI  - Does DNA methylation provide a link between folate and neural tube closure?

PMID- 30215550
TI  - The feasibility of synthetic MRI in breast cancer patients: comparison of T2
      relaxation time with multiecho spin echo T2 mapping method.
AB  - OBJECTIVE:: To compare the T2 relaxation times acquired with synthetic MRI to
      those of multi-echo spin-echo sequences and to evaluate the usefulness of
      synthetic MRI in the clinical setting. METHODS:: From January 2017 to May 2017,
      we included 51 patients with newly diagnosed breast cancer, who underwent
      additional synthetic MRI and multiecho spin echo (MESE) T2 mapping sequences.
      Synthetic MRI technique uses a multiecho and multidelay acquisition method for
      the simultaneous quantification of physical properties such as T1 and T2
      relaxation times and proton density image map. A radiologist with 9 years of
      experience in breast imaging drew region of interests manually along the tumor
      margins on two consecutive axial sections including the center of tumor mass and
      in the fat tissue of contralateral breast on both synthetic T2 map and MESE T2
      map images. RESULTS:: The mean T2 relaxation time of the cancer was 84.75 ms (+/-
      15.54) by synthetic MRI and 90.35 ms (+/- 19.22) by MESE T2 mapping. The mean T2
      relaxation time of the fat was 129.22 ms (+/- 9.53) and 102.11 ms (+/- 13.9),
      respectively. Bland-Altman analysis showed mean difference of 8.4 ms for the
      breast cancer and a larger mean difference of 27.8 ms for the fat tissue.
      Spearman's correlation test showed that there was significant positive
      correlation between synthetic MRI and MESE sequences for the cancer (r = 0.713, p
      < 0.001) and for the fat (r = 0.551, p < 0.001). The positive estrogen receptor
      and low histologic grade were associated with little differences between two
      methods (p = 0.02  and = 0.043, respectively). CONCLUSION:: T2 relaxation times
      of breast cancer acquired with synthetic MRI showed positive correlation with
      those of MESE T2 mapping. Synthetic MRI could be useful for the evaluation of
      tissue characteristics by simultaneous acquisition of several quantitative
      physical properties. ADVANCES IN KNOWLEDGE:: Synthetic MRI is useful for the
      evaluation of T2 relaxation times of the breast cancers.

PMID- 30215551
TI  - The Role of Weight Management in the Treatment of Adult Obstructive Sleep Apnea.
      An Official American Thoracic Society Clinical Practice Guideline.
AB  - BACKGROUND: Overweight/obesity is a common, reversible risk factor for
      obstructive sleep apnea severity (OSA). The purpose of this guideline is to
      provide evidence-based recommendations for the management of overweight/obesity
      in patients with OSA. METHODS: The Grading of Recommendations, Assessment,
      Development and Evaluation approach was used to evaluate the literature. Clinical
      recommendations were formulated by a panel of pulmonary, sleep medicine, weight
      management, and behavioral science specialists. RESULTS: Behavioral,
      pharmacological, and surgical treatments promote weight loss and can reduce OSA
      severity, reverse common comorbidities, and improve quality of life, although
      published studies have methodological limitations. After considering the quality
      of evidence, feasibility, and acceptability of these interventions, the panel
      made a strong recommendation that patients with OSA who are overweight or obese
      be treated with comprehensive lifestyle intervention consisting of 1) a reduced
      calorie diet, 2) exercise or increased physical activity, and 3) behavioral
      guidance. Conditional recommendations were made regarding reduced-calorie diet
      and exercise/increased physical activity as separate management tools.
      Pharmacological therapy and bariatric surgery are appropriate for selected
      patients who require further assistance with weight loss. CONCLUSIONS: Weight
      loss interventions, especially comprehensive lifestyle interventions, are
      associated with improvements in OSA severity, cardiometabolic comorbidities, and
      quality of life. The American Thoracic Society recommends that clinicians
      regularly assess weight and incorporate weight management strategies that are
      tailored to individual patient preferences into the routine treatment of adult
      patients with OSA who are overweight or obese.

PMID- 30215552
TI  - Protracted Bacterial Bronchitis (PBB) in Children.

PMID- 30215553
TI  - Removal of giant intraosseous meningioma followed by cranioplasty using a custom
      made bioceramic implant: case report.
AB  - Intraosseous meningioma of the chordoid type is a rare clinical entity. Radical
      surgical removal and subsequent cranioplasty is the treatment of choice. Here,
      the authors report a severe case involving more than 70% of the calvarial surface
      area, which was removed and repaired using a prefabricated custom-made, titanium
      reinforced, bioceramic implant and bone-cutting guides. Tumor removal and good
      esthetic outcome were achieved, along with a 17.1% increase of intracranial
      volume. Bioceramic implants have shown promising initial results and may
      represent an important new tool in the surgeon's armamentarium.

PMID- 30215554
TI  - Extreme lateral transodontoid approach to the ventral craniocervical junction:
      cadaveric dissection and case illustrations.
AB  - OBJECTIVE Surgical treatment of pathological processes involving the ventral
      craniocervical junction (CCJ) traditionally involves anterior and posterolateral
      skull base approaches. In cases of bilateral extension, when lesions extend
      beyond the midline to the contralateral side, a unilateral corridor may result in
      suboptimal resection. In these cases, the lateral extent of the tumor will
      prevent extirpation of the lesion via anterior surgical approaches. The authors
      describe a unilateral operative corridor developed along an extreme lateral
      trajectory to the anterior aspect of the clival and upper cervical dura, allowing
      exposure and resection of tumor on the contralateral side. This approach is used
      when the disease involves the bone structures inherent to stability at the
      anterior CCJ. METHODS To achieve exposure of the ventral CCJ, an extreme lateral
      transcondylar transodontoid (ELTO) approach was performed with transposition of
      the ipsilateral vertebral artery, followed by drilling of the C1 anterior arch.
      Resection of the odontoid process allowed access to the contralateral component
      of lesions across the midline to the region of the extracranial contralateral
      vertebral artery, maximizing resection. RESULTS Exposure and details of the
      surgical procedure were derived from anatomical cadavers. At the completion of
      cadaveric dissection, morphometric measurements of the relevant anatomical
      landmarks were obtained. Illustrative case examples for approaching ventral CCJ
      chordomas via the ELTO approach are presented. CONCLUSIONS The ELTO approach
      provides a safe and direct surgical corridor to treat complex lesions at the
      ventral CCJ with bilateral extension through a single operative corridor. This
      approach can be combined with other lateral approaches or posterior infratemporal
      approaches to remove more extensive lesions involving the rostral clivus, jugular
      foramen, and temporal bone.

PMID- 30215555
TI  - Clinical and ophthalmological outcome of endoscopic transorbital surgery for
      cranioorbital tumors.
AB  - OBJECTIVE Cranioorbital tumors are complex lesions that involve the deep orbit,
      floor of the frontal bone, and lesser and greater wing of the sphenoid bone. The
      purpose of this study was to describe the clinical and ophthalmological outcomes
      with an endoscopic transorbital approach (TOA) in the management of cranioorbital
      tumors involving the deep orbit and intracranial compartment. METHODS The authors
      performed endoscopic TOAs via the superior eyelid crease incision in 18 patients
      (16 TOA alone and 2 TOA combined with a simultaneous endonasal endoscopic
      resection) with cranioorbital tumors from September 2016 to November 2017. There
      were 12 patients with sphenoorbital meningiomas. Other lesions included
      osteosarcoma, plasmacytoma, sebaceous gland carcinoma, intraconal schwannoma,
      cystic teratoma, and fibrous dysplasia. Ten patients had primary lesions and 8
      patients had recurrent tumors. Thirteen patients had intradural lesions, while 5
      had only extradural lesions. RESULTS Of 18 patients, 7 patients underwent gross
      total resection of the tumor and 7 patients underwent planned near-total
      resection of the tumor, leaving the cavernous sinus lesion. Subtotal resection
      was performed in 4 patients with recurrent tumors. There was no postoperative CSF
      leak requiring reconstruction surgery. Fourteen of 18 patients (77.8%) had
      preoperative proptosis on the ipsilateral side, and all 14 patients had
      improvement in exophthalmos; the mean proptosis reduced from 5.7 +/- 2.7 mm to
      1.5 +/- 1.4 mm. However, some residual proptosis was evident in 9 of the 14
      (64%). Ten of 18 patients (55.6%) had preoperative optic neuropathy, and 6 of
      them (60.0%) had improvement; the median best-corrected visual acuity improved
      from 20/100 to 20/40. Thirteen of 18 patients showed mild ptosis at an immediate
      postoperative examination, all of whom had a spontaneous and complete recovery of
      their ptosis during the follow-up period. Three of 7 patients showed improvement
      in extraocular motility after surgery. CONCLUSIONS Endoscopic TOA can be
      considered as an option in the management of cranioorbital tumors involving
      complex anatomical areas, with acceptable sequelae and morbidity.

PMID- 30215556
TI  - An estimation of global volume of surgically treatable epilepsy based on a
      systematic review and meta-analysis of epilepsy.
AB  - OBJECTIVE Epilepsy is one of the most common neurological disorders, yet its
      global surgical burden has yet to be characterized. The authors sought to compile
      the most current epidemiological data to quantify global prevalence and
      incidence, and estimate global surgically treatable epilepsy. Understanding
      regional and global epilepsy trends and potential surgical volume is crucial for
      future policy efforts and resource allocation. METHODS The authors performed a
      systematic literature review and meta-analysis to determine the global incidence,
      lifetime prevalence, and active prevalence of epilepsy; to estimate surgically
      treatable epilepsy volume; and to evaluate regional trends by WHO regions and
      World Bank income levels. Data were extracted from all population-based studies
      with prespecified methodological quality across all countries and demographics,
      performed between 1990 and 2016 and indexed on PubMed, EMBASE, and Cochrane. The
      current and annual new case volumes for surgically treatable epilepsy were
      derived from global epilepsy prevalence and incidence. RESULTS This systematic
      review yielded 167 articles, across all WHO regions and income levels. Meta
      analysis showed a raw global prevalence of lifetime epilepsy of 1099 per 100,000
      people, whereas active epilepsy prevalence is slightly lower at 690 per 100,000
      people. Global incidence was found to be 62 cases per 100,000 person-years. The
      meta-analysis predicted 4.6 million new cases of epilepsy annually worldwide, a
      prevalence of 51.7 million active epilepsy cases, and 82.3 million people with
      any lifetime epilepsy diagnosis. Differences across WHO regions and country
      incomes were significant. The authors estimate that currently 10.1 million
      patients with epilepsy may be surgical treatment candidates, and 1.4 million new
      surgically treatable epilepsy cases arise annually. The highest prevalences are
      found in Africa and Latin America, although the highest incidences are reported
      in the Middle East and Latin America. These regions are primarily low- and middle
      income countries; as expected, the highest disease burden falls
      disproportionately on regions with the fewest healthcare resources. CONCLUSIONS
      Understanding of the global epilepsy burden has evolved as more regions have been
      studied. This up-to-date worldwide analysis provides the first estimate of
      surgical epilepsy volume and an updated comprehensive overview of current
      epidemiological trends. The disproportionate burden of epilepsy on low- and
      middle-income countries will require targeted diagnostic and treatment efforts to
      reduce the global disparities in care and cost. Quantifying global epilepsy
      provides the first step toward restructuring the allocation of healthcare
      resources as part of global healthcare system strengthening.

PMID- 30215557
TI  - A rat study of the use of end-to-side peripheral nerve repair as a "babysitting"
      technique to reduce the deleterious effect of chronic denervation.
AB  - OBJECTIVE Functional recovery is disappointing after surgical repair of nerves
      that are injured far from their target organs and/or after delayed repair. In the
      former case, a nerve transfer that transects a distal nerve fascicle to innervate
      denervated targets is one strategy to promote nerve regeneration and functional
      recovery. An alternate strategy tested in this study is to perform an end-to-side
      neurorrhaphy to "babysit" (protect) the denervated distal nerve stump at the time
      of nerve repair and reduce the deleterious effect of chronic denervation on nerve
      regeneration. METHODS In the hindlimbs of Sprague-Dawley rats, the common
      peroneal (CP) nerve was transected unilaterally and the distal CP nerve stump
      inserted through a perineurial window into the intact tibial (TIB) nerve, i.e.,
      CP-TIB end-to-side neurorrhaphy. In the first experiment, TIB nerve motoneurons
      that had regenerated and/or sprouted axons into the CP nerve within 3 months were
      stimulated to elicit contractions, and thereafter, identified with retrograde
      dyes for counting. In the second experiment, the intact TIB nerve was transected
      and cross-sutured to a 3-month chronically denervated distal CP nerve stump that
      had either been "protected" by ingrown TIB nerves after CP-TIB neurorrhaphy or
      remained chronically denervated. Thereafter, the number of retrogradely labeled
      TIB nerve motoneurons that had regenerated their nerves within 3 months were
      counted and reinnervated tibialis anterior (TA) muscles weighed. RESULTS A mean
      (+/- SE) of 231 +/- 83 TIB nerve motoneurons grew into the end-to-side CP distal
      nerve stump with corresponding ankle flexion; 32% regenerated their axons and 24%
      sprouted axons from the intact TIB nerve, eliciting ankle flexor-extensor co
      contraction. In the second experiment, after a 3-month period of TIB nerve
      regeneration, significantly more TIB motoneurons regenerated their axons into
      "protected" than "unprotected" CP distal nerve stumps within 3 months (mean 332
      +/- 43.6 vs 235 +/- 39.3 motoneurons) with corresponding and significantly higher
      numbers of regenerated nerve fibers, resulting in significantly better recovery
      of reinnervated TA muscle weight. CONCLUSIONS These experiments in rats
      demonstrated that delayed nerve repair is more effective when the deleterious
      effects of chronic denervation of the distal nerve stump are reduced by
      protecting the nerve stump with ingrowing nerve fibers across an end-to-side
      insertion of the distal nerve stump into a neighboring intact nerve. Such an end
      to-side neurorrhaphy may be invaluable as a means of preventing the atrophy of
      distal nerve stumps and target organs after chronic denervation, which allows for
      effective reinnervation of the protected distal nerve stumps and target organs
      over distance and time.

PMID- 30215558
TI  - Growth hormone and prolactin-staining tumors causing acromegaly: a retrospective
      review of clinical presentations and surgical outcomes.
AB  - OBJECTIVE Acromegaly results in disfiguring growth and numerous medical
      complications. This disease is typically caused by growth hormone (GH)-secreting
      pituitary adenomas, which are treated first by resection, followed by radiation
      and/or medical therapy if needed. A subset of acromegalics have dual-staining
      pituitary adenomas (DSPAs), which stain for GH and prolactin. Presentations and
      treatment outcomes for acromegalics with DSPAs are not well understood. METHODS
      The authors retrospectively reviewed the records of more than 5 years of
      pituitary adenomas resected at their institution. Data were collected on
      variables related to clinical presentation, tumor pathology, radiological size,
      and disease recurrence. The Fisher's exact test, ANOVA, Student t-test, chi
      square test, and Cox proportional hazards and multiple logistic regression were
      used to measure statistical significance. RESULTS Of 593 patients with pituitary
      adenoma, 91 presented with acromegaly. Of these 91 patients, 69 (76%) had tumors
      that stained for GH only (single-staining somatotrophic adenomas [SSAs]), while
      22 (24%) had tumors that stained for GH and prolactin (DSPAs). Patients with
      DSPAs were more likely to present with decreased libido (p = 0.012), signs of
      acromegalic growth (p = 0.0001), hyperhidrosis (p = 0.0001), and headaches (p =
      0.043) than patients with SSAs. DSPAs presented with significantly higher serum
      prolactin (60.7 vs 10.0 ug/L, p = 0.0002) and insulin-like growth factor-1 (IGF
      1) (803.6 vs 480.0 ng/ml, p = 0.0001), and were more likely to have IGF-1 levels
      > 650 ng/ml (n = 13 [81.3%] vs n = 6 [21.4%], p = 0.0001) than patients with SSAs
      despite similar sizes (1.8 vs 1.7 cm, p = 0.5). Patients with DSPAs under 35
      years of age were more likely to have a recurrence (n = 4 [50.0%] vs n = 3
      [11.1%], p = 0.01) than patients with SSAs under the age of 35. DSPA patients
      were less likely to achieve remission with surgery than SSA patients (n = 2 [20%]
      vs n = 19 [68%], p = 0.01). Univariate analysis identified single-staining tumors
      (p = 0.02), gross-total resection (p = 0.02), and tumor diameter (p = 0.05) as
      predictors of surgical remission. Multiple logistic regression demonstrated that
      SSAs (p = 0.04) were independently associated with surgical remission of
      acromegaly. Kaplan-Meier analysis revealed that DSPAs had more time until disease
      remission (p = 0.033). CONCLUSIONS Acromegalics with tumors that stain for
      prolactin and GH, which represented almost a quarter of acromegalics in this
      cohort, had more aggressive clinical presentations and postoperative outcomes
      than SSAs. Prolactin staining provides useful information for acromegalics
      undergoing pituitary surgery.

PMID- 30215559
TI  - Intracranial pressure elevations in diffuse axonal injury: association with
      nonhemorrhagic MR lesions in central mesencephalic structures.
AB  - OBJECTIVE Increased intracranial pressure (ICP) in patients with severe traumatic
      brain injury (TBI) with diffuse axonal injury (DAI) is not well defined. This
      study investigated the occurrence of increased ICP and whether clinical factors
      and lesion localization on MRI were associated with increased ICP in patients
      with DAI. METHODS Fifty-two patients with severe TBI (median age 24 years, range
      9-61 years), who had undergone ICP monitoring and had DAI on MRI, as determined
      using T2*-weighted gradient echo, susceptibility-weighted imaging, and diffusion
      weighted imaging (DWI) sequences, were enrolled. The proportion of good
      monitoring time (GMT) with ICP > 20 mm Hg during the first 120 hours postinjury
      was calculated and associations with clinical and MRI-related factors were
      evaluated using linear regression. RESULTS All patients had episodes of ICP > 20
      mm Hg. The mean proportion of GMT with ICP > 20 mm Hg was 5%, and 27% of the
      patients (14/52) spent more than 5% of GMT with ICP > 20 mm Hg. The Glasgow Coma
      Scale motor score at admission (p = 0.04) and lesions on DWI sequences in the
      substantia nigra and mesencephalic tegmentum (SN-T, p = 0.001) were associated
      with the proportion of GMT with ICP > 20 mm Hg. In multivariable linear
      regression, lesions on DWI sequences in SN-T (8% of GMT with ICP > 20 mm Hg, 95%
      CI 3%-13%, p = 0.004) and young age (-0.2% of GMT with ICP > 20 mm Hg, 95% CI 
      0.07% to -0.3%, p = 0.002) were associated with increased ICP. CONCLUSIONS
      Increased ICP occurs in approximately one-third of patients with severe TBI who
      have DAI. Age and lesions on DWI sequences in the central mesencephalon (i.e., SN
      T) are associated with elevated ICP. These findings suggest that MR lesion
      localization may aid prediction of increased ICP in patients with DAI.

PMID- 30215560
TI  - Surgical management of camptocormia in Parkinson's disease: systematic review and
      meta-analysis.
AB  - OBJECTIVE Camptocormia is a potentially debilitating condition in the progression
      of Parkinson's disease (PD). It is described as an abnormal forward flexion while
      standing that resolves when lying supine. Although the condition is relatively
      common, the underlying pathophysiology and optimal treatment strategy are
      unclear. In this study, the authors systematically reviewed the current surgical
      management strategies for camptocormia. METHODS PubMed was queried for primary
      studies involving surgical intervention for camptocormia in PD patients. Studies
      were excluded if they described nonsurgical interventions, provided only
      descriptive data, or were case reports. Secondarily, data from studies describing
      deep brain stimulation (DBS) to the subthalamic nuclei were extracted for
      potential meta-analysis. Variables showing correlation to improvement in sagittal
      plane bending angle (i.e., the vertical angle caused by excessive kyphosis) were
      subjected to formal meta-analysis. RESULTS The query resulted in 9 studies
      detailing treatment of camptocormia: 1 study described repetitive trans-spinal
      magnetic stimulation (rTSMS), 7 studies described DBS, and 1 study described
      deformity surgery. Five studies were included for meta-analysis. The total number
      of patients was 66. The percentage of patients with over 50% decrease in sagittal
      plane imbalance with DBS was 36.4%. A duration of camptocormia of 2 years or less
      was predictive of better outcomes (OR 4.15). CONCLUSIONS Surgical options include
      transient, external spinal stimulation; DBS targeting the subthalamic nuclei; and
      spinal deformity surgery. Benefit from DBS stimulation was inconsistent. Spine
      surgery corrected spinal imbalance but was associated with a high complication
      rate.

PMID- 30215561
TI  - Entrapped ulnar nerve by flexor carpi ulnaris tendon: case illustration.

PMID- 30215563
TI  - Growth and rupture of unruptured intracranial aneurysms.
AB  - OBJECTIVE Risk factors for growth of unruptured intracranial aneurysms (UIAs)
      during a lifelong follow-up in relation to subsequent rupture are unknown. The
      author's aim in this study was to investigate whether risk factors for UIA growth
      are different for those that lead to rupture than for those that do not. METHODS
      The series consists of 87 patients with 111 UIAs diagnosed before 1979, when UIAs
      were not treated. A total follow-up time of the patients was 2648 person-years
      for all-cause death and 2182 years when patients were monitored until the first
      rupture, death due to unrelated causes, or the last contact (annual incidence of
      aneurysm rupture, 1.2%). The follow-up time between aneurysm measurements was
      1669 person-years. Risk factors for UIA growth were analyzed in relation to
      subsequent rupture. RESULTS The median follow-up time between aneurysm
      measurements was 21.7 years (range 1.2-51.0 years). In 40 of the 87 patients
      (46%), the UIAs increased in size >= 1 mm, and in 31 patients (36%) >= 3 mm. All
      ruptured aneurysms in 27 patients grew during the follow-up of 324 person-years
      (mean growth rates 6.1 mm, 0.92 mm/year, and 37%/year), while growth without
      rupture occurred in 13 patients during 302 follow-up years (3.9 mm, 0.18 mm/year,
      and 4%/year) and no growth occurred in 47 patients during 1043 follow-up years.
      None of the 60 patients without aneurysm rupture experienced one during the
      subsequent 639 follow-up years after the last aneurysm measurement. Independent
      risk factors for UIA growth (>= 1 mm) in all patients were female sex (adjusted
      OR 3.08, 95% CI 1.04-9.13) and smoking throughout the follow-up time (adjusted OR
      3.16, 95% CI 1.10-9.10), while only smoking (adjusted OR 4.36, 95% CI 1.27-14.99)
      was associated with growth resulting in aneurysm rupture. Smoking was the only
      independent risk factor for UIA growth >= 3 mm resulting in aneurysm rupture
      (adjusted OR 4.03, 95% CI 1.08-15.07). Cigarette smoking at baseline predicted
      subsequent UIA growth, while smoking at the end of the follow-up was associated
      with growth resulting in aneurysm rupture. CONCLUSIONS Cigarette smoking is an
      important risk factor for UIA growth, particularly for growth resulting in
      rupture. Cessation of smoking may reduce the risk of devastating aneurysm growth.

PMID- 30215562
TI  - Routine screening for hepatitis C viral infection in patients undergoing elective
      cranial neurosurgery.
AB  - OBJECTIVE Undiagnosed hepatitis C virus (HCV) and HIV in patients present risks
      of transmission of bloodborne infections to surgeons intraoperatively.
      Presurgical screening has been suggested as a protocol to protect surgical staff
      from these pathogens. The authors sought to determine the incidence of HCV and
      HIV infection in elective craniotomy patients and analyze the cost-effectiveness
      of universal and risk factor-specific screening for protection of the surgical
      staff. METHODS All patients undergoing elective craniotomy between July 2009 and
      July 2016 at the National Brain Aneurysm Center who did not refuse screening were
      included in this study. The authors utilized rapid HCV and HIV tests to screen
      patients prior to elective surgery, and for each patient who tested positive
      using the rapid HCV or HIV test, qualitative nucleic acid testing was used to
      confirm active viral load, and risk factor information was collected. Patients
      scheduled for nonurgent surgery who were found to be HCV positive were referred
      to a hepatologist for preoperative treatment. The authors compared risk factors
      between patients who tested positive on rapid tests, patients with active viral
      loads, and a random sample of patients who tested negative. The authors also
      tracked the clinical and material costs of HCV and HIV rapid test screening per
      patient for cost-effectiveness analysis and calculated the cost per positive
      result of screening all patients and of screening based on all patient risk
      factors that differed significantly between patients with and those without
      positive HCV test results. RESULTS The study population of patients scheduled for
      elective craniotomy included 1461 patients, of whom 22 (1.5%) refused the
      screening. Of the 1439 patients screened, 15 (1.0%) tested positive for HCV using
      rapid HCV screening; 9 (60%) of these patients had active viral loads. No patient
      (0%) tested positive for HIV. Seven (77.8%) of the 9 patients with active viral
      loads underwent treatment with a hepatologist and were referred back for surgery
      3-6 months after sustained virologic response to treatment, but the remaining 2
      patients (22.2%) required urgent surgery. Of the 9 patients with active viral
      loads, 1 patient (11%) had a history of both intravenous drug abuse and tattoos.
      Two of the 9 patients (22%) had tattoos, and 3 (33%) were born within the age
      screening bracket (born 1945-1965) recommended by the Centers for Disease Control
      and Prevention. Rates of smoking differed significantly (p < 0.001) between
      patients who had active viral loads of HCV and patients who were HCV negative,
      and rates of smoking (p < 0.001) and IV drug abuse (p < 0.01) differed
      significantly between patients who were HCV rapid-test positive and those who
      were HCV negative. Total screening costs (95% CI) per positive result were
      $3,877.33 ($2,348.05-$11,119.28) for all patients undergoing HCV rapid screening,
      $226.29 ($93.54-$312.68) for patients with a history of smoking, and $72.00
      ($29.15-$619.39) for patients with a history of IV drug abuse. CONCLUSIONS The
      rate of undiagnosed HCV infection in this patient population was commensurate
      with national levels. While the cost of universal screening was considerable,
      screening patients based on a history of smoking or IV drug abuse would likely
      reduce costs per positive result greatly and potentially provide cost-effective
      identification and treatment of HCV patients and surgical staff protection. HIV
      screening found no infected patients and was not cost-effective.

PMID- 30215564
TI  - Letter to the Editor. Atypical pituitary adenoma.

PMID- 30215565
TI  - Developing an optimal follow-up strategy based on the natural history of
      nonfunctioning pituitary adenomas.
AB  - OBJECTIVE The natural history and proper algorithm for follow-up testing of
      nonfunctioning pituitary adenomas (PAs) are not well known, despite their
      relatively high prevalence. The aim of this study was to suggest the optimal
      follow-up algorithm for nonfunctioning PAs based on their natural history.
      METHODS The authors followed up 197 patients with nonfunctioning PAs that had not
      been treated (including surgery and radiation therapy) at the time of detection,
      in a single center, between March 2000 and February 2017. They conducted a
      hormone test, visual field test, and MRI at the time of diagnosis and yearly
      thereafter. RESULTS The overall median follow-up duration was 37 months.
      Microadenomas (n = 38) did not cause visual disturbance, pituitary apoplexy, or
      endocrine dysfunction. The incidence of patients with tumor volume growth >= 20%
      was higher for macroadenomas than microadenomas (13.8 vs 5.0 per 100 person-years
      [PYs], p = 0.002). The median time to any tumor growth was 4.8 years (95% CI 3.4
      4.8 years) for microadenomas and 4 years (95% CI 3.3-4.2 years) for
      macroadenomas. The overall incidence of worsening visual function was 0.69 per
      100 PYs. Patients with a tumor volume growth rate >= 0.88 cm3/year (n = 20) had a
      higher incidence of worsening visual function (4.69 vs 0.30 per 100 PYs, p <
      0.001). The tumor growth rate of all microadenomas was < 0.88 cm3/year. The
      median time to tumor growth >= 20% was 3.3 years (95% CI 1.8-3.9 years) in
      patients with a tumor growth rate >= 0.88 cm3/year and 4.9 years (95% CI 4.6-7.2
      years) in patients with a tumor growth rate < 0.88 cm3/year. CONCLUSIONS The
      authors have devised a follow-up strategy based on the tumor volume growth rate
      as well as initial tumor volume. In patients with microadenomas, the next MRI
      study can be performed at 3 years. In patients with macroadenomas, the second MRI
      study should be performed between 6 months and 1 year to assess the tumor growth
      rate. In patients with a tumor growth rate >= 0.88 cm3/year, the MRI study should
      be performed within 2 years. In patients with a tumor growth rate < 0.88
      cm3/year, the MRI study can be delayed until 4 years.

PMID- 30215566
TI  - Results of Gamma Knife anterior capsulotomy for refractory obsessive-compulsive
      disorder: results in a series of 10 consecutive patients.
AB  - OBJECTIVE Obsessive-compulsive disorder (OCD) is a severe psychiatric condition.
      The authors present their experience with Gamma Knife radiosurgery (GKRS) in the
      treatment of patients with OCD resistant to any medical therapy. METHODS Patients
      with severe OCD resistant to all pharmacological and psychiatric treatments who
      were treated with anterior GKRS capsulotomy were retrospectively reviewed. These
      patients were submitted to a physical, neurological, and neuropsychological
      examination together with structural and functional MRI before and after GKRS
      treatment. Strict study inclusion criteria were applied. Radiosurgical
      capsulotomy was performed using two 4-mm isocenters targeted at the midputaminal
      point of the anterior limb of the capsule. A maximal dose of 120 Gy was
      prescribed for each side. Clinical global changes were assessed using the
      Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF)
      scale, EQ-5D, Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory
      (STAI). OCD symptoms were determined by the Yale-Brown Obsessive Compulsive Scale
      (Y-BOCS). RESULTS Ten patients with medically refractory OCD (5 women and 5 men)
      treated between 2006 and 2015 were included in this study. Median age at
      diagnosis was 22 years, median duration of illness at the time of radiosurgery
      was 14.5 years, and median age at treatment was 38.8 years. Before GKRS, the
      median Y-BOCS score was 34.5 with a median obsession score of 18 and compulsion
      score of 17. Seven (70%) of 10 patients achieved a full response at their last
      follow-up, 2 patients were nonresponders, and 1 patient was a partial responder.
      Evaluation of the Y-BOCS, BDI, STAI-Trait, STAI-State, GAF, and EQ-5D showed
      statistically significant improvement at the last follow-up after GKRS.
      Neurological examinations were normal in all patients at each visit. At last
      follow-up, none of the patients had experienced any significant adverse
      neuropsychological effects or personality changes. CONCLUSIONS GKRS anterior
      capsulotomy is effective and well tolerated with a maximal dose of 120 Gy. It
      reduces both obsessions and compulsions, improves quality of life, and diminishes
      depression and anxiety.

PMID- 30215567
TI  - "Reinventing the wheel": reflections on a recurrent phenomenon in the history of
      neurosurgery.

PMID- 30215568
TI  - Corrigendum: Do Men and Women Know What They Want? Sex Differences in Online
      Daters' Educational Preferences.

PMID- 30215569
TI  - From vaccines to global health to vaccines.

PMID- 30215570
TI  - EFab domain substitution as a solution to the light-chain pairing problem of
      bispecific antibodies.
AB  - Bispecific antibody therapeutics can expand the functionality of a conventional
      monoclonal antibody drug because they can bind multiple antigens. However, their
      great potential is counterbalanced by the challenges faced in their production.
      The classic asymmetric bispecific containing an Fc requires the expression of
      four unique chains - two light chains and two heavy chains; each light chain must
      pair with its correct heavy chain, which then must heterodimerize to form the
      full bispecific. The light-chain pairing problem has several solutions, some of
      which require engineering and optimization for each bispecific pair. Here, we
      introduce a technology called EFab Domain Substitution, which replaces the
      Cepsilon2 of IgE for one of the CL/CH1 domains into one arm of an asymmetric
      bispecific to encourage the correct pairing of the light chains. EFab Domain
      Substitution provides very robust correct pairing while maintaining antibody
      function and is effective for many variable domains. We report its effect on the
      biophysical properties of an antibody and the crystal structure of the EFab
      domain substituted into the adalimumab Fab (PDB ID 6CR1).

PMID- 30215571
TI  - Experiences and perceptions about undergoing mammographic screening: a
      qualitative study involving women from a county in Sweden.
AB  - PURPOSE:  An organized population-based mammographic screening programme aims for
      an early detection of potential breast abnormalities so that treatment can
      commence. Continuous participation and a high attendance rate are vital for an
      effective programme. It is important to understand the underlying reasons for
      participation in mammographic screening, should there be factors that are
      amendable within reason and could be adjusted. Therefore, the invited women are
      valuable sources of information. This study aimed at describing the experiences
      and perceptions about mammographic screening of women from three municipalities
      in a Swedish county. METHOD:  Six semi-structured focus-group discussions, each
      with four to five participants, were held. Content analysis was then conducted.
      RESULTS:  The screening procedure, such as staff professionalism, was covered.
      Other people's opinions and the woman's own understanding affected the women's
      decisions on whether or not to undergo the procedure. Structural conditions, such
      as travel time and financial issues, were sources of concern. However, the offer
      to perform mammographic screening was perceived with gratitude. CONCLUSIONS: 
      Structural conditions, risk and time perceptions, the screening procedure,
      attitudes towards undergoing it and appreciation of its benefit may influence the
      women's continuous willingness to be screened, which in turn may affect public
      and individual health.

PMID- 30215572
TI  - Wandering as a Sociomaterial Practice: Extending the Theorization of GPS Tracking
      in Cognitive Impairment.
AB  - Electronic tracking through global positioning systems (GPSs) is used to monitor
      people with cognitive impairment who "wander" outside the home. This ethnographic
      study explored how GPS-monitored wandering was experienced by individuals, lay
      carers, and professional staff. Seven in-depth case studies revealed that
      wandering was often an enjoyable and worthwhile activity and helped deal with
      uncertainty and threats to identity. In what were typically very complex care
      contexts, GPS devices were useful to the extent that they aligned with a wider
      sociomaterial care network that included lay carers, call centers, and health and
      social care professionals. In this context, "safe" wandering was a collaborative
      accomplishment that depended on the technology's materiality, affordances, and
      aesthetic properties; a distributed knowledge of the individual and the places
      they wandered through, and a collective and dynamic interpretation of risk.
      Implications for design and delivery of GPS devices and services for cognitive
      impairment are discussed.

PMID- 30215573
TI  - Spongispora temasekensis, a new boletoid genus and species from Singapore.
AB  - Dipterocarp forests are a typical and widespread type of vegetation in tropical
      lowlands of southeast Asia that harbor a high diversity of ectomycorrhizal fungi,
      including boletes. Based on molecular and morphological characters, a unique
      bolete found in Singapore associated with the dipterocarp Hopea odorata was
      proven to represent a new species in the proposed new genus Spongispora.
      Phylogenetic analyses of five loci indicate that Spongispora is nested in the
      subfamily Leccinoideae of the Boletaceae, most closely related to an inclusive
      clade of Leccinum, Leccinellum, Octaviania, Rossbeevera, and Turmalinea. However,
      genetic distances between Spongispora and genera in Leccinoideae are mostly
      higher than that between any two known genera in this subfamily, which supports
      the proposal of a new genus. Spongispora temasekensis is characterized by a
      whitish to pale yellow hymenophore that stains brown where injured, coarsely
      reticulate stipe, interwoven trichodermial pileipellis, and broadly elliptical to
      ovoid basidiospores with sponge-like ornamentation perforated by irregular
      clefts, cracks, and warts under scanning electron microscopy. Morphological
      descriptions, illustrations, and comparisons with allied taxa are made, and a key
      to the genera of the subfamily Leccinoideae is provided.

PMID- 30215574
TI  - New neotropical species of Phyllachorales based on molecular, morphological, and
      ecological data.
AB  - Species of tropical tar spot fungi (Phyllachorales, Ascomycota) are obligate
      biotrophic plant parasitic fungi associated with living leaves of a wide range of
      families of host plants, mainly in tropical and subtropical regions. In this
      study, samples of tropical tar spot fungi were collected in forests in Costa Rica
      and Panama. To identify taxa, we used morphology and information on host plants
      and combined multigene phylogeny of four genes: the large subunit nuclear
      ribosomal DNA (28S rDNA), the small subunit nuclear ribosomal DNA (18S rDNA), the
      complete internal transcribed spacer region of ribosomal DNA (nuc rDNA ITS1-5.8S
      ITS2; ITS), and the translation elongation factor 1-alpha (tef1). Here we propose
      one new species in the genus Camarotella and eight new species in Telimena with
      their morphological descriptions, illustrations, and sequence data. The newly
      described species are Camarotella licaniae on Licania arborea (Chrysobalanaceae)
      and in the genus Telimena: T. billiae on Billia rosea (Sapindaceae), T. drymoniae
      on Drymonia multiflora (Gesneriaceae), T. hydrangeae on Hydrangea sp.
      (Hydrangeaceae), T. miravallensis on Symplocos panamensis (Symplocaceae), T.
      protii on Protium sp. (Burseraceae), T. rinoreae on Rinorea sp. (Violaceae), T.
      semialarii on Semialarium mexicanum (Celastraceae), and T. triseptata on Tapirira
      mexicana (Anacardiaceae). The new name Telimena nitens on Schlegelia brachyanta
      (Schlegeliaceae) is presented and 10 species of Phyllachora are transferred to
      Telimena, leading to the new combinations T. canarii, T. galavisii, T. insueta,
      T. ruelliae, T. scutiformis, T. serjaniicola, T. spicatae, T. subrepens, T.
      symploci, and T. symplocicola. Additionally, revisions of tar spot fungi on host
      families Burseraceae, Sapindaceae, and Symplocaceae are provided, and four new
      synonyms are proposed.

PMID- 30215575
TI  - It's Not Only Who You Are but Who You Are With: High School Composition and
      Individuals' Attainment Over the Life Course.
AB  - We examined life-course effects of attending selective schools using a
      longitudinal study of U.S. high school students begun in 1960 ( Ns ranging from
      1,952 to 377,015). The effects, measured 11 and 50 years after the initial
      assessment, differed significantly across the two indicators of school
      selectivity that were used. School average socioeconomic background was
      positively related to students' educational expectations, educational attainment,
      income, and occupational prestige at the 11-year follow-up (0.15 <= beta <= 0.39;
      all ps < .001). Conversely, schools' average achievement at the 11-year follow-up
      was negatively related to students' expectations, attainment, income, and
      occupational prestige (-0.42 <= beta <= -0.05; all ps < .05) when schools'
      socioeconomic background was controlled for. All associations were mediated by
      students' educational expectations. With the exception of income, these effects
      were consistent 50 years after high school, pointing to the long reach of
      beneficial learning resources and negative social comparison processes when
      attending selective schools.

PMID- 30215576
TI  - Assessment of occupational exposure to airborne chlorine dioxide of healthcare
      workers using impregnated wipes during high-level disinfection of non-lumened
      flexible nasoendoscopes.
AB  - Routine flexible nasoendoscopy in otolaryngology clinics is well established, the
      rate-limiting step of which being the speed of the nasoendoscopes reprocessing
      method used. Non-lumened flexible nasoendoscopes are expensive, heat-sensitive,
      delicate instruments that cannot be sterilized in an autoclave but must be
      disinfected by means of high level disinfection (HLD). In one of the public
      hospitals in Singapore, the method of disinfection was recently changed to the
      use of commercial impregnated wipes which generates less than 1% chlorine dioxide
      upon activation. An exposure assessment was performed to assess the potential
      exposure of healthcare workers (HCWs) to airborne chlorine dioxide during
      nasoendoscope disinfection. A total of fourteen long-term personal samples, four
      short-term personal samples and sixteen long-term area samples were collected
      over eight days in midget impingers containing 0.02% potassium iodide in sodium
      carbonate/sodium bicarbonate buffer during the nasoendoscope disinfection. The
      samples were then analyzed by ion-chromatograph. The chlorine dioxide
      concentrations and upper confidence limit at 95% confidence level (UCL95%) for
      personal and area samples collected were all below the occupational exposure
      limits (OEL) for chlorine dioxide (Singapore workplace Safety and Health PELs,
      ACGIH TLVs, U.S. OSHA PELs). The study presented evidence that the exposure of
      HCWs to chlorine dioxide during high-level disinfection of flexible
      nasoendoscopes were deemed insignificant.

PMID- 30215577
TI  - Experimental investigation of tribological characteristics and emissions with
      nonedible sunflower oil as a biolubricant.
AB  - Plant (vegetable) oil has been evaluated as a substitute for mineral oil-based
      lubricants because of its natural and environmentally friendly characteristics.
      Availability of vegetable oil makes it a renewable source of bio-oils.
      Additionally, vegetable oil-based lubricants have shown potential for reducing
      hydrocarbon and carbon dioxide (CO2) emissions when utilized in internal
      combustion (IC) engines and industrial operations. In this study, sunflower oil
      was investigated to study its lubricant characteristics under different loads
      using the four-ball tribometer and the exhaust emissions were tested using a four
      stroke, single-cylinder diesel engine. All experimental works conformed to
      American Society for Testing and Materials standard (ASTM D4172-B). Under low
      loads, sunflower oil showed adequate tribological characteristics (antifriction
      and antiwear) compared with petroleum oil samples. The results also demonstrated
      that the sunflower oil-based lubricant was more effective in reducing the
      emission levels of carbon monoxide (CO), CO2, and hydrocarbons under different
      test conditions. Therefore, sunflower oil has the potential to be used as
      lubricant of mating components. Implications: An experimental investigation of
      the characteristics of nonedible sunflower oil tribological behaviors and
      potential as a renewable source for biofluids alternative to the petroleum oils
      was carried out. The level of emissions of a four-stroke, single-cylinder diesel
      engine using sunflower oil as a biolubricant was evaluated.

PMID- 30215578
TI  - Rotavirus vaccine efficacy: current status and areas for improvement.
AB  - The difference noted in Rotavirus vaccine efficiency between high and low income
      countries correlates with the lack of universal access to clean water and higher
      standards of hygiene. Overcoming these obstacles will require great investment
      and also time, therefore more effective vaccines should be developed to meet the
      needs of those who would benefit the most from them. Increasing our current
      knowledge of mucosal immunity, response to Rotavirus infection and its modulation
      by circadian rhythms could point at actionable pathways to improve vaccination
      efficacy, especially in the case of individuals affected by environmental
      enteropathy. Also, a better understanding and validation of Rotavirus entry
      factors as well as the systematic monitoring of dominant strains could assist in
      tailoring vaccines to individual's needs. Another aspect that could improve
      vaccine efficiency is targeting to M cells, for which new ligands could
      potentially be sought. Finally, alternative mucosal adjuvants and vaccine
      expression, storage and delivery systems could have a positive impact in the
      outcome of Rotavirus vaccination.

PMID- 30215579
TI  - Identifying and naming the currently known diversity of the genus Hydnum, with an
      emphasis on European and North American taxa.
AB  - In this study, 49 species of Hydnum are recognized worldwide. Twenty-two of them
      are described here as new species. Epitypes are proposed for H. repandum and H.
      rufescens. The majority of the species are currently known only from a single
      continent. The barcodes produced in this study are deposited in the RefSeq
      database and used as a basis to name species hypotheses in UNITE. Eleven
      infrageneric clades recovered in a phylogenetic analysis are supported by
      morphological characteristics and formally recognized: subgenera Alba, Hydnum,
      Pallida, and Rufescentia; sections Hydnum, Olympica, Magnorufescentia, and
      Rufescentia; and subsections Mulsicoloria, Rufescentia, and Tenuiformia.

PMID- 30215580
TI  - Removal of fluoride in aqueous medium under the optimum conditions through
      intracellular accumulation in Bacillus flexus (PN4).
AB  - The removal of fluoride is essential for water contaminated with fluoride before
      being utilized since the unsafe concentration of fluoride with respect to the
      permissible limits. In the present study, there are 61 bacterial strains
      belonging to fluoride tolerance were isolated from the contaminated soil of
      Dharmapuri District, Tamil Nadu, India and they were evaluated for different
      characterization. Among the strains isolated, the strain PN4 showed a high
      tolerance to fluoride ranging from 500 to 2500 ppm under different stress
      conditions. The strain PN4 was selected as a possible organism for the
      degradation and removal of fluoride in an aqueous medium. Based on the
      morphology, biochemical characteristics and the 16S rRNA sequencing, the
      bacterium PN4 was identified as Bacillus flexus. In batch mode studies, the
      glucose was showed the maximum removal of fluoride (86%) followed by beef extract
      (82%) and a significant level of defluoridation was observed at pH 7.0 and the
      temperature at 35 degrees C. In the antibiotic-resistance pattern, the strain
      Bacillus flexus PN4 was shown sensitive to three different antibiotics.
      Intracellular accumulation of fluoride by the bacterial cell was characterized by
      SEM- EDAX, TEM and FTIR analysis.

PMID- 30215581
TI  - Identifying a new subtype of multiple sclerosis.
AB  - Dr Bruce Trapp and Dr Daniel Ontaneda speak to Laura Dormer, Commissioning
      Editor: Bruce D Trapp, PhD, is a Chair of the Department of Neurosciences at the
      Lerner Research Institute, Cleveland Clinic (OH, USA) and Professor of Molecular
      Medicine at Case Western Reserve University (OH, USA). Dr Trapp received his PhD
      from Loyola University Stritch School of Medicine in Chicago (IL, USA). Dr
      Trapp's research investigates the cause of neurological disability in multiple
      sclerosis patients, cellular mechanism of brain repair in neurodegenerative
      diseases and the molecular biology of myelination in the central and peripheral
      nervous systems. Daniel Ontaneda, MD, is a staff neurologist at the Cleveland
      Clinic Mellen Center for Multiple Sclerosis. Dr Ontaneda earned his MD from the
      Universidad Catolica del Ecuador and MSc in clinical research from Case Western
      Reserve University. He completed a postdoctoral fellowship at Baylor College of
      Medicine, followed by neurology and neuroimmunology training at the Cleveland
      Clinic. His specialties include acute disseminated encephalomyelitis, Devic's
      disease (neuromyelitis optica), multiple sclerosis, neuroimmunology, optic
      neuritis and transverse myelitis.

PMID- 30215582
TI  - The development of a staphylococcus aureus four antigen vaccine for use prior to
      elective orthopedic surgery.
AB  - Staphylococcus aureus (S. aureus) is a challenging bacterial pathogen which can
      cause a range of diseases, from mild skin infections, to more serious and
      invasive disease including deep or organ space surgical site infections, life
      threatening bacteremia, and sepsis. S. aureus rapidly develops resistance to
      antibiotic treatments. Despite current infection control measures, the burden of
      disease remains high. The most advanced vaccine in clinical development is a 4
      antigen S. aureus vaccine (SA4Ag) candidate that is being evaluated in a phase
      2b/3 efficacy study in patients undergoing elective spinal fusion surgery
      (STaphylococcus aureus suRgical Inpatient Vaccine Efficacy [STRIVE]). SA4Ag has
      been shown in early phase clinical trials to be generally safe and well
      tolerated, and to induce high levels of bactericidal antibodies in healthy
      adults. In this review we discuss the design of SA4Ag, as well as the proposed
      clinical development plan supporting licensure of SA4Ag for the prevention of
      invasive disease caused by S. aureus in elective orthopedic surgical populations.
      We also explore the rationale for the generalizability of the results of the
      STRIVE efficacy study (patients undergoing elective open posterior multilevel
      instrumented spinal fusion surgery) to a broad elective orthopedic surgery
      population due to the common pathophysiology of invasive S. aureus disease and
      commonalties of patient and procedural risk factors for developing postoperative
      S. aureus surgical site infections.

PMID- 30215583
TI  - A phase III clinical trial to evaluate the safety and immunogenicity of 23-valent
      pneumococcal polysaccharide vaccine (PPV23) in healthy children, adults, and
      elderly.
AB  - To evaluate the safety and immunogenicity of a newly 23-valent pneumococcal
      polysaccharide vaccine (PPV23), a phase III clinical trial was conducted in
      population aged >= 2 years. We conducted a randomized, double-blinded, active
      controlled trial, in which 1760 participants were randomly assigned in a 1:1
      ratio to receive one dose of either the test vaccine or the control commercial
      vaccine. The surveillance period was 28 days. The 2-fold increase rate of anti
      pneumococcal for 23 serotypes varied from 49.71% to 90.96% in the treatment group
      and from 44.52% to 88.24% in the control group. According to -10% non-inferiority
      margin and 95% confidence intervals of rate difference, all the 23 serotypes of
      the treatment group were non-inferiority to the control group. The 2-fold
      increase rate of anti-pneumococcal antibody were significantly higher in the
      treatment group for 11 serotypes including 1, 2, 3, 4, 10A, 11A, 14, 18C, 20,
      22F, and 23F. Serious adverse events occurred in 2 in 879 (0.23%) participants in
      the treatment group and 2 in 880 (0.23%) participants in the control group, and
      all the adverse events were unrelated to the vaccination. The overall adverse
      reaction frequency showed no difference between the treatment (51.19%) and
      control group (47.95%), and most adverse reactions were mild or moderate in
      intensity. The newly PPV23 is immunologically non-inferior to the control
      commercial vaccine and well tolerated in healthy Chinese population aged >= 2
      years. Trial registration: ClinicalTrial.gov identifier: NCT02451969.

PMID- 30215584
TI  - Development of best practices to minimize wound complications after complex
      tethered spinal cord surgery: a modified Delphi study.
AB  - OBJECTIVE Complications after complex tethered spinal cord (cTSC) surgery include
      infections and cerebrospinal fluid (CSF) leaks. With little empirical evidence to
      guide management, there is variability in the interventions undertaken to limit
      complications. Expert-based best practices may improve the care of patients
      undergoing cTSC surgery. Here, authors conducted a study to identify consensus
      driven best practices. METHODS The Delphi method was employed to identify
      consensual best practices. A literature review regarding cTSC surgery together
      with a survey of current practices was distributed to 17 board-certified
      pediatric neurosurgeons. Thirty statements were then formulated and distributed
      to the group. Results of the second survey were discussed during an in-person
      meeting leading to further consensus, which was defined as >= 80% agreement on a
      4-point Likert scale (strongly agree, agree, disagree, strongly disagree).
      RESULTS Seventeen consensus-driven best practices were identified, with all
      participants willing to incorporate them into their practice. There were four
      preoperative interventions: (1, 2) asymptomatic AND symptomatic patients should
      be referred to urology preoperatively, (3, 4) routine preoperative urine cultures
      are not necessary for asymptomatic AND symptomatic patients. There were nine
      intraoperative interventions: (5) patients should receive perioperative cefazolin
      or an equivalent alternative in the event of allergy, (6) chlorhexidine-based
      skin preparation is the preferred regimen, (7) saline irrigation should be used
      intermittently throughout the case, (8) antibiotic-containing irrigation should
      be used following dural closure, (9) a nonlocking running suture technique should
      be used for dural closure, (10) dural graft overlay should be used when unable to
      obtain primary dural closure, (11) an expansile dural graft should be
      incorporated in cases of lipomyelomeningocele in which primary dural closure does
      not permit free flow of CSF, (12) paraxial muscles should be closed as a layer
      separate from the fascia, (13) routine placement of postoperative drains is not
      necessary. There were three postoperative interventions: (14) postoperative
      antibiotics are an option and, if given, should be discontinued within 24 hours;
      (15) patients should remain flat for at least 24 hours postoperatively; (16)
      routine use of abdominal binders or other compressive devices postoperatively is
      not necessary. One intervention was prioritized for additional study: (17)
      further study of additional gram-negative perioperative coverage is needed.
      CONCLUSIONS A modified Delphi technique was used to develop consensus-driven best
      practices for decreasing wound complications after cTSC surgery. Further study is
      required to determine if implementation of these practices will lead to reduced
      complications. Discussion through the course of this study resulted in the
      initiation of a multicenter study of gram-negative surgical site infections in
      cTSC surgery.

PMID- 30215585
TI  - Spatial regulation of gene expression in nonsyndromic sagittal craniosynostosis.
AB  - OBJECTIVE Cranial suture patterning and development are highly regulated
      processes that are not entirely understood. While studies have investigated the
      differential gene expression for different sutures, little is known about gene
      expression changes during suture fusion. The aim of this study was to examine
      gene expression in patent, fusing, and fused regions along sagittal suture
      specimens in nonsyndromic craniosynostosis patients. METHODS Sagittal sutures
      were collected from 7 patients (average age 4.5 months) who underwent minimally
      invasive craniotomies at the Children's Hospital of Richmond at VCU under IRB
      approval. The sutures were analyzed using micro-CT to evaluate patency. The areas
      were classified as open, fusing, or fused and were harvested, and mRNA was
      isolated. Gene expression for bone-related proteins, osteogenic and angiogenic
      factors, transforming growth factor-beta (TGF-beta) superfamily, and Wnt
      signaling was analyzed using quantitative polymerase chain reaction and compared
      with normal sutures collected from fetal demise tissue (control). RESULTS Micro
      CT demonstrated that there are variable areas of closure along the length of the
      sagittal suture. When comparing control samples to surgical samples, there was a
      significant difference in genes for Wnt signaling, TGF-beta, angiogenic and
      osteogenic factors, bone remodeling, and nuclear rigidity in mRNA isolated from
      the fusing and fused areas of the sagittal suture compared with patent areas (p <
      0.05). CONCLUSIONS In nonsyndromic sagittal craniosynostosis, the affected suture
      has variable areas of being open, fusing, and fused. These specific areas have
      different mRNA expression. The results suggest that BMP-2, FGFR3, and several
      other signaling pathways play a significant role in the regulation of suture
      fusion as well as in the maintenance of patency in the normal suture.

PMID- 30215586
TI  - Long-term follow-up for patients with infantile hydrocephalus treated by choroid
      plexus coagulation.
AB  - OBJECTIVE Shunt surgery is the most common treatment for hydrocephalus, but it is
      associated with several long-term complications. Endoscopic choroid plexus
      coagulation (CPC) and endoscopic third ventriculostomy (ETV) are alternative
      surgeries that may avoid the need for shunt surgery. Although the short-term
      efficacy and safety of CPC have been reported in previous studies, long-term
      outcome, including not only avoiding shunt placement but also intellectual
      development, remains to be elucidated. The purpose of the present study was to
      investigate the long-term outcome of CPC. METHODS The study population comprised
      patients who had infantile hydrocephalus treated by endoscopic CPC before the age
      of 24 months and who were followed until at least 5 years of age. Retrospective
      review was performed using the medical charts. The authors assessed educational
      status and the full-scale intelligence quotient (FSIQ) using the Wechsler
      Intelligence Scale for Children (WISC) IV as the means to evaluate the
      intellectual development. RESULTS Fourteen patients with infantile hydrocephalus
      underwent CPC with or without ETV as a primary surgery. There were no
      intraoperative complications. In 7 patients (50%), hydrocephalus was successfully
      controlled without shunt placement. Six patients (43%) eventually required shunt
      placement. In one patient hydrocephalus was controlled by additional ETV. In the
      shunt-independent group, 4 patients went to age-appropriate school or achieved
      age-appropriate development according to intelligence quotient (IQ), 1 patient
      went to specialized school, and 2 patients had disabilities. In the shunt
      dependent group, 4 patients went to an age-appropriate school or achieved age
      appropriate development by IQ, 1 patient went to specialized school, and 1
      patient had disabilities. The mean FSIQ score in 3 patients without shunts was 90
      (range 89-91) and the mean FSIQ score in 4 patients with shunts was 80 (range 48
      107). There was no significant difference in the rate of normal development
      between the shunt-independent group and the shunt-dependent group (p = 0.72).
      CONCLUSIONS The CPC with or without ETV can be a safe and effective treatment in
      children with infantile hydrocephalus. Long-term control of hydrocephalus and
      normal intellectual development can be achieved in successful cases. Further
      prospective studies should be required to elucidate appropriate indications.

PMID- 30215587
TI  - Variation in the management of isolated craniosynostosis: a survey of the
      Synostosis Research Group.
AB  - OBJECTIVE The authors created a collaborative network, the Synostosis Research
      Group (SynRG), to facilitate multicenter clinical research on craniosynostosis.
      To identify common and differing practice patterns within the network, they
      assessed the SynRG surgeons' management preferences for sagittal synostosis.
      These results will be incorporated into planning cooperative studies. METHODS The
      SynRG consists of 12 surgeons at 5 clinical sites. An email survey was
      distributed to SynRG surgeons in late 2016, and responses were collected through
      early 2017. Responses were collated and analyzed descriptively. RESULTS All of
      the surgeons-7 plastic/craniofacial surgeons and 5 neurosurgeons-completed the
      survey. They varied in both experience (1-24 years) and sagittal synostosis case
      volume in the preceding year (5-45 cases). Three sites routinely perform
      preoperative CT scans. The preferred surgical technique for children younger than
      3 months is strip craniectomy (10/12 surgeons), whereas children older than 6
      months are all treated with open cranial vault surgery. Pre-incision cefazolin,
      preoperative complete blood count panels, and an arterial line were used by most
      surgeons, but tranexamic acid was used routinely at 3 sites and never at the
      other 2 sites. Among surgeons performing endoscopic strip craniectomy surgery
      (SCS), most create a 5-cm-wide craniectomy, whereas 2 surgeons create a 2-cm
      strip. Four surgeons routinely send endoscopic SCS patients to the intensive care
      unit after surgery. Two of the 5 sites routinely obtain a CT scan within the 1st
      year after surgery. CONCLUSIONS The SynRG surgeons vary substantially in the use
      of imaging, the choice of surgical procedure and technique, and follow-up. A
      collaborative network will provide the opportunity to study different practice
      patterns, reduce variation, and contribute multicenter data on the management of
      children with craniosynostosis.

PMID- 30215588
TI  - Three-dimensional printing and neuroendovascular simulation for the treatment of
      a pediatric intracranial aneurysm: case report.
AB  - The use of simulators has been described in a variety of fields as a training
      tool to gain technical skills through repeating and rehearsing procedures in a
      safe environment. In cerebrovascular surgery, simulation of skull base approaches
      has been used for decades. The use of simulation in neurointervention to acquire
      and enhance skills before treating a patient is a newer concept, but its
      utilization has been limited due to the lack of good models and deficient
      haptics. The advent of 3D printing technology and the development of new training
      models has changed this landscape. The prevalence of aneurysms in the pediatric
      population is much lower than in adults, and concepts and tools sometimes have to
      be adapted from one population to another. Neuroendovascular rehearsal is a valid
      strategy for the treatment of complex aneurysms, especially for the pediatric
      population. The authors present the case of an 8-year-old boy with a fusiform
      intracranial aneurysm and documented progressive growth, who was successfully
      treated after the authors rehearsed the placement of a flow diverter using a
      patient-specific 3D-printed replicator system model.

PMID- 30215589
TI  - Does patient selection account for the perceived cost savings in outpatient spine
      surgery? A meta-analysis of current evidence and analysis from an administrative
      database.
AB  - OBJECTIVE From 1994 to 2006 outpatient spinal surgery increased 5-fold. The
      perceived cost savings with outcomes comparable to or better than those achieved
      with inpatient admission for the same procedures are desirable in an era where
      health expenditures are scrutinized. The increase in outpatient spine surgery is
      also driven by the proliferation of ambulatory surgery centers. In this study,
      the authors hypothesized that the total savings in outpatient spine surgery is
      largely driven by patient selection and biases toward healthier patients. METHODS
      A meta-analysis assessed patient selection factors and outcomes associated with
      outpatient spine procedures. Pooled odds ratios and mean differences were
      calculated using a Bayesian random-effects model. The authors extended this
      analysis in a novel way by using the results of the meta-analysis to examine cost
      data from an administrative database of academically affiliated hospitals. A
      Bayesian approach with priors informed by the meta-analysis was used to compare
      costs for inpatient and outpatient performance of anterior cervical discectomy
      and fusion (ACDF) and lumbar laminectomy. RESULTS Sixteen studies with a total of
      370,195 patients met the inclusion criteria. Outpatient procedures were
      associated with younger patient age (mean difference [MD] -2.34, 95% credible
      interval [CrI] -4.39 to -0.34) and no diabetes diagnosis (odds ratio [OR] 0.78,
      95% CrI 0.54-0.97). Outpatient procedures were associated with a lower likelihood
      of reoperation (OR 0.42, 95% CrI 0.16-0.80), 30-day readmission (OR 0.39, 95% CrI
      0.16-0.74), and complications (OR 0.29, 95% CrI 0.15-0.50) and with lower overall
      costs (MD -$121,392.72, 95% CrI -$216,824.81 to -$23,632.92). Additional analysis
      of the national administrative data revealed more modest cost savings than those
      found in the meta-analysis for outpatient spine surgeries relative to inpatient
      spine surgeries. Estimated cost savings for both younger patients ($555 for those
      age 30-35 years [95% CrI -$733 to -$374]) and older patients ($7290 for those age
      65-70 years [95% CrI -$7380 to -$7190]) were less than the overall cost savings
      found in the meta-analysis. CONCLUSIONS Compared to inpatient spine surgery,
      outpatient spine surgery was associated with better short-term outcomes and an
      initial reduction in direct costs. A selection bias for outpatient procedures
      toward younger, healthier patients may confound these results. The additional
      analysis of the national database suggests that cost savings in the outpatient
      setting may be less than previously reported and a result of outpatient
      procedures being offered more frequently to younger and healthier individuals.

PMID- 30215590
TI  - The relationship between surgical site drains and reoperation for wound-related
      complications following posterior cervical spine surgery: a multicenter
      retrospective study.
AB  - OBJECTIVE Use of surgical site drains following posterior cervical spine surgery
      is variable, and its impact on outcomes remains controversial. Studies of drain
      use in the lumbar spine have suggested that drains are not associated with
      reduction of reoperations for wound infection or hematoma. There is a paucity of
      studies examining this relationship in the cervical spine, where hematomas and
      infections can have severe consequences. This study aims to examine the
      relationship between surgical site drains and reoperation for wound-related
      complications following posterior cervical spine surgery. METHODS This study is a
      multicenter retrospective review of 1799 consecutive patients who underwent
      posterior cervical decompression with instrumentation at 4 tertiary care centers
      between 2004 and 2016. Demographic and perioperative data were analyzed for
      associations with drain placement and return to the operating room. RESULTS Of
      1799 patients, 1180 (65.6%) had a drain placed. Multivariate logistic regression
      analysis identified history of diabetes (OR 1.37, p = 0.03) and total number of
      levels operated (OR 1.32, p < 0.001) as independent predictors of drain
      placement. Rates of reoperation for any surgical site complication were not
      different between the drain and no-drain groups (4.07% vs 3.88%, p = 0.85).
      Similarly, rates of reoperation for surgical site infection (1.61% vs 2.58%, p =
      0.16) and hematoma (0.68% vs 0.48%, p = 0.62) were not different between the
      drain and no-drain groups. However, after adjusting for history of diabetes and
      the number of operative levels, patients with drains had significantly lower odds
      of returning to the operating room for surgical site infection (OR 0.48, p =
      0.04) but not for hematoma (OR 1.22, p = 0.77). CONCLUSIONS This large study
      characterizes current practice patterns in the utilization of surgical site
      drains during posterior cervical decompression and instrumentation. Patients with
      drains placed did not have lower odds of returning to the operating room for
      postoperative hematoma. However, the authors' data suggest that patients with
      drains may be less likely to return to the operating room for surgical site
      infection, although the absolute number of infections in the entire population
      was small, limiting the analysis.

PMID- 30215591
TI  - Origins of eponymous instruments in spine surgery.
AB  - Every day, spine surgeons call for instruments named after surgical pioneers. Few
      know the designers or the histories behind their instruments. In this paper the
      authors provide a historical perspective on the Penfield dissector, Leksell
      rongeur, Hibbs retractor, Woodson elevator, Kerrison rongeur, McCulloch
      retractor, Caspar pin retractor system, and Cloward handheld retractor, and a
      biographical review of their inventors. Historical data were obtained by
      searching the HathiTrust Digital Library, PubMed, Google Scholar, Google Books,
      and Google, and personal communications with relatives, colleagues, and
      foundations of the surgeon-designers. The authors found that the Penfield
      dissectors filled a need for delicate tools for manipulating the brain and that
      the Leksell rongeur increased surgical efficiency during war-related
      laminectomies. Hibbs' retractor facilitated his spine fusion technique. Woodson
      was both a dentist and a physician whose instrument was adopted by spine
      surgeons. Kerrison rongeurs were developed in otology to decompress bone near the
      facial nerve. The McCulloch, Caspar, and Cloward retractors helped improve
      exposure during the emergence of new techniques, i.e., microdiscectomy and
      anterior cervical discectomy and fusion. The histories behind these eponymous
      instruments remind us that innovation sometimes begins in other specialties and
      demonstrate the role of innovation in improving patient care.

PMID- 30215592
TI  - Redefining lumbar spinal stenosis as a developmental syndrome: an MRI-based
      multivariate analysis of findings in 709 patients throughout the 16- to 82-year
      age spectrum.
AB  - OBJECTIVE Using an imaging-based prospective comparative study of 709 eligible
      patients that was designed to assess lumbar spinal stenosis (LSS) in the ages
      between 16 and 82 years, the authors aimed to determine whether they could
      formulate radiological structural differences between the developmental and
      degenerative types of LSS. METHODS MRI structural changes were prospectively
      reviewed from 2 age cohorts of patients: those who presented clinically before
      the age of 60 years and those who presented at 60 years or older. Categorical
      degeneration variables at L1-S1 segments were compared. A multivariate
      comparative analysis of global radiographic degenerative variables and spinal
      dimensions was conducted in both cohorts. The age at presentation was correlated
      as a covariable. RESULTS A multivariate analysis demonstrated no significant
      between-groups differences in spinal canal dimensions and stenosis grades in any
      segments after age was adjusted for. There were no significant variances between
      the 2 cohorts in global degenerative variables, except at the L4-5 and L5-S1
      segments, but with only small effect sizes. Age-related degeneration was found in
      the upper lumbar segments (L1-4) more than the lower lumbar segments (L4-S1).
      These findings challenge the notion that stenosis at L4-5 and L5-S1 is mainly
      associated with degenerative LSS. CONCLUSIONS Integration of all the morphometric
      and qualitative characteristics of the 2 LSS cohorts provides evidence for a
      developmental background for LSS. Based on these findings the authors propose the
      concept of LSS as a developmental syndrome with superimposed degenerative
      changes. Further studies can be conducted to clarify the clinical definition of
      LSS and appropriate management approaches.

PMID- 30215593
TI  - Preemptive analgesia for postoperative pain relief in thoracolumbosacral spine
      operations: a double-blind, placebo-controlled randomized trial.
AB  - OBJECTIVE Preemptive administration of analgesic medication is more effective
      than medication given after the onset of the painful stimulus. The efficacy of
      preoperative or preemptive pain relief after thoracolumbosacral spine surgery has
      not been well studied. The present study was a double-blind, placebo-controlled
      randomized trial of preemptive analgesia with a single-shot epidural injection in
      adult patients undergoing spine surgery. METHODS Ninety-nine adult patients
      undergoing thoracolumbosacral operations via a posterior approach were randomized
      to receive a single shot of either epidural placebo (group 1), hydromorphone
      alone (group 2), or bupivacaine with hydromorphone (group 3) before surgery at
      the preoperative holding area. The primary outcome was the presence of opioid
      sparing and rescue time-defined as the time interval from when a patient was
      extubated to the time pain medication was first demanded during the postoperative
      period. Secondary outcomes include length of stay at the postanesthesia care unit
      (PACU), pain score at the PACU, opioid dose, and hospital length of stay. RESULTS
      Of the 99 patients, 32 were randomized to the epidural placebo group, 33 to the
      hydromorphone-alone group, and 34 to the bupivacaine with hydromorphone group. No
      significant difference was seen across the demographics and surgical complexities
      for all 3 groups. Compared to the control group, opioid sparing was significantly
      higher in group 2 (57.6% vs 15.6%, p = 0.0007) and group 3 (52.9% vs 15.6%, p =
      0.0045) in the first demand of intravenous hydromorphone as a supplemental
      analgesic medication. Compared to placebo, the rescue time was significantly
      higher in group 2 (187 minutes vs 51.5 minutes, p = 0.0014) and group 3 (204.5
      minutes vs 51. minutes, p = 0.0045). There were no significant differences in
      secondary outcomes. CONCLUSIONS The authors' study demonstrated that preemptive
      analgesia in thoracolumbosacral surgeries can significantly reduce analgesia
      requirements in the immediate postoperative period as evidenced by reduced
      request for opioid medication in both analgesia study groups who received a
      preoperative analgesic epidural. Nonetheless, the lack of differences in pain
      score and opioid dose at the PACU brings into question the role of preemptive
      epidural opioids in spine surgery patients. Further work is necessary to
      investigate the long-term effectiveness of preemptive epidural opioids and their
      role in pain reduction and patient satisfaction. Clinical trial registration no.:
      NCT02968862 (clinicaltrials.gov).

PMID- 30215594
TI  - Halorubrum chaoviator Mancinelli et al. 2009 is a later, heterotypic synonym of
      Halorubrum ezzemoulense Kharroub et al. 2006. Emended description of Halorubrum
      ezzemoulense Kharroub et al. 2006.
AB  - A polyphasic comparative taxonomic study of Halorubrum ezzemoulense Kharroub et
      al. 2006, Halorubrum chaoviator Mancinelli et al. 2009 and eight new Halorubrum
      strains related to these haloarchaeal species was carried out. Multilocus
      sequence analysis using the five concatenated housekeeping genes atpB, EF-2,
      glnA, ppsA and rpoB', and phylogenetic analysis based on the 757 core protein
      sequences obtained from their genomes showed that Hrr. ezzemoulense DSM 17463T,
      Hrr. chaoviator Halo-G*T (=DSM 19316T) and the eight Halorubrum strains formed a
      robust cluster, clearly separated from the remaining species of the genus
      Halorubrum. The orthoANI value and digital DNA-DNA hybridization value,
      calculated by the Genome-to-Genome Distance Calculator (GGDC), showed percentages
      among Hrr. ezzemoulense DSM 17463T, Hrr. chaoviator DSM 19316T and the eight
      Halorubrum strains ranging from 99.4 to 97.9 %, and from 95.0 to 74.2 %,
      respectively, while these values for those strains and the type strains of the
      most closely related species of Halorubrum were 88.7-77.4 % and 36.1-22.3 %,
      respectively. Although some differences were observed, the phenotypic and polar
      lipid profiles were quite similar for all the strains studied. Overall, these
      data show that Hrr. ezzemoulense, Hrr. chaoviator and the eight new Halorubrum
      isolates constitute a single species. Thus, Hrr. chaoviator should be considered
      as a later, heterotypic synonym of Hrr. ezzemoulense. We propose an emended
      description of Hrr. ezzemoulense, including the features of Hrr. chaoviator and
      those of the eight new isolates.

PMID- 30215595
TI  - Production of a Beet chlorosis virus full-length cDNA clone by means of Gibson
      assembly and analysis of biological properties.
AB  - Beet chlorosis virus (genus Polerovirus, family Luteoviridae), which is
      persistently transmitted by the aphid Myzus persicae, is part of virus yellows in
      sugar beet and causes interveinal yellowing as well as significant yield loss in
      Beta vulgaris. To allow reverse genetic studies and replace vector transmission,
      an infectious cDNA clone under cauliflower mosaic virus 35S control in a binary
      vector for agrobacterium-mediated infection was constructed using Gibson
      assembly. Following agroinoculation, the BChV full-length clone was able to
      induce a systemic infection of the cultivated B. vulgaris. The engineered virus
      was successfully aphid-transmitted when acquired from infected B. vulgaris and
      displayed the same host plant spectrum as wild-type virus. This new polerovirus
      infectious clone is a valuable tool to identify the viral determinants involved
      in host range and study BChV protein function, and can be used to screen sugar
      beet for BChV resistance.

PMID- 30215596
TI  - Blastococcus litoris sp. nov., isolated from sea-tidal flat sediment.
AB  - A novel Gram-strain-positive, non-spore-forming bacterial strain, designated GP
      S2-8T, was isolated from a sea-tidal flat sediment sample from Gopado, Republic
      of Korea. Cells were aerobic, catalase-negative, oxidase-positive, non-motile and
      cocci, occurring singly, in pairs or in tetrads, and often tending to form
      aggregates. The strain grew at 4-45  degrees C (optimum, 28-37  degrees C), at pH
      4.0-11.0 (pH 7.0-9.0) and in the presence of 0-11 % (w/v) NaCl (0-3 %).
      Phylogenetic analyses based on 16S rRNA gene sequences represented that the
      isolate belongs to the genus Blastococcus. The diagnostic diamino acid in the
      cell-wall peptidoglycan was meso-diaminopimelic acid. Whole-cell sugar analysis
      of strain GP-S2-8T revealed rhamnose, glucose and mannose as characteristic
      sugars. The predominant respiratory quinone was MK-9(H4) and the major fatty
      acids were iso-C16 : 0, iso-C16 : 1 H, summed feature 3 (C16 : 1omega7c and/or
      C16 : 1omega6c), iso-C15 : 0 and iso-C14 : 0. The polar lipid profile included
      diphosphadidylglycerol, phosphatidylethanolamine, phosphatidylcholine,
      phosphatidylinositol, one unidentified glycophospholipid, two unidentified
      phospholipids and five unidentified lipids. The DNA G+C content was 74.2 mol%.
      DNA-DNA relatedness values between strain GP-S2-8T and type strains of the genus
      Blastococcus ranged from 14.6 to 48.6 %. On the basis of the phenotypic
      differences and DNA-DNA relatedness data, the isolate represents a new species of
      the genus Blastococcus, for which the name Blastococcuslitoris sp. nov. is
      proposed. The type strain is GP-S2-8T (=KCCM 43275T=JCM 32354T=DSM 106127T=KCTC
      49078T).

PMID- 30215598
TI  - Shedding light on stellate cells.
AB  - The relationship between grid cells and two types of neurons found in the medial
      entorhinal cortex has been clarified.

PMID- 30215597
TI  - Functional properties of stellate cells in medial entorhinal cortex layer II.
AB  - Layer II of the medial entorhinal cortex (MEC) contains two principal cell types:
      pyramidal cells and stellate cells. Accumulating evidence suggests that these two
      cell types have distinct molecular profiles, physiological properties, and
      connectivity. The observations hint at a fundamental functional difference
      between the two cell populations but conclusions have been mixed. Here, we used a
      tTA-based transgenic mouse line to drive expression of ArchT, an optogenetic
      silencer, specifically in stellate cells. We were able to optogenetically
      identify stellate cells and characterize their firing properties in freely moving
      mice. The stellate cell population included cells from a range of functional cell
      classes. Roughly one in four of the tagged cells were grid cells, suggesting that
      stellate cells contribute not only to path-integration-based representation of
      self-location but also have other functions. The data support observations
      suggesting that grid cells are not the sole determinant of place cell firing.

PMID- 30215600
TI  - Be aware, innate immune cells remember.

PMID- 30215602
TI  - The coding potential of circRNAs.

PMID- 30215599
TI  - Fertility Among Female Survivors of Childhood, Adolescent, and Young Adult
      Cancer: Protocol for Two Pan-European Studies (PanCareLIFE).
AB  - BACKGROUND: Despite a significant number of studies on female fertility following
      childhood, adolescent, and young adult (CAYA) cancer, studies establishing
      precise (dose-related) estimates of treatment-related risks are still scarce.
      Previous studies have been underpowered, did not include detailed treatment
      information, or were based on self-report only without any hormonal assessments.
      More precise assessments of who is at risk for sub- or infertility are needed.
      OBJECTIVE: The objective of our study is to describe the design and methods of 2
      studies on female fertility (a cohort study and a nested case-control study)
      among female survivors of CAYA cancer performed within the European PanCareLIFE
      project. METHODS: For the cohort study, which aims to evaluate the overall risk
      of fertility impairment, as well as the risk for specific subgroups of female
      CAYA cancer survivors, 13 institutions from 9 countries provide data on fertility
      impairment. Survivors are defined as being fertility impaired if they meet at
      least one of 8 different criteria based on self-reported and hormonal data. For
      the nested case-control study, which aims to identify specific treatment-related
      risk factors associated with fertility impairment in addition to possible dose
      response relationships, cases (fertility impaired survivors) are selected from
      the cohort study and matched to controls (survivors without fertility impairment)
      on a 1:2 basis. RESULTS: Of the 10,964 survivors invited for the cohort study,
      data are available from 6619 survivors, either questionnaire-based only (n=4979),
      hormonal-based only (n=72), or both (n=1568). For the nested case-control study,
      a total of 450 cases and 882 controls are identified. CONCLUSIONS: Results of
      both PanCareLIFE fertility studies will provide detailed insight into the risk of
      fertility impairment following CAYA cancer and diagnostic- or treatment-related
      factors associated with an increased risk. This will help clinicians to
      adequately counsel both girls and young women, who are about to start anticancer
      treatment, as well as adult female CAYA cancer survivors, concerning future
      parenthood and to timely refer them for fertility preservation. Ultimately, we
      aim to empower patients and survivors and improve their quality of life.
      REGISTERED REPORT IDENTIFIER: RR1-10.2196/10824.

PMID- 30215601
TI  - Sumoylation-deficient Prdx6 repairs aberrant Sumoylation-mediated Sp1
      dysregulation-dependent Prdx6 repression and cell injury in aging and oxidative
      stress.
AB  - Progressive deterioration of antioxidant response in aging is a major culprit in
      the initiation of age-related pathobiology induced by oxidative stress. We
      previously reported that oxidative stress leads to a marked reduction in
      transcription factor Sp1 and its mediated Prdx6 expression in lens epithelial
      cells (LECs) leading to cell death. Herein, we examined how Sp1 activity goes
      awry during oxidative stress/aging, and whether it is remediable. We found that
      Sp1 is hyper-Sumoylated at lysine (K) 16 residue in aging LECs. DNA binding and
      promoter assays revealed, in aging and oxidative stress, a significant reduction
      in Sp1 overall binding, and specifically to Prdx6 promoter.
      Expression/overexpression assay revealed that the observed reduction in Sp1-DNA
      binding activity was connected to its hyper-Sumoylation due to increased reactive
      oxygen species (ROS) and Sumo1 levels, and reduced levels of Senp1, Prdx6 and
      Sp1. Mutagenesis of Sp1 at K16R (arginine) residue restored steady-state, and
      improved Sp1-DNA binding activity and transactivation potential. Extrinsic
      expression of Sp1K16R increased cell survival and reduced ROS levels by
      upregulating Prdx6 expression in LECs under aging/oxidative stress, demonstrating
      that Sp1K16R escapes the aberrant Sumoylation processes. Intriguingly, the
      deleterious processes are reversible by the delivery of Sumoylation-deficient
      Prdx6, an antioxidant, which would be a candidate molecule to restrict aging
      pathobiology.

PMID- 30215604
TI  - Closed-loop system to enhance slow-wave activity.
AB  - OBJECTIVE: Recent evidence reports cognitive, metabolic, and sleep restoration
      benefits resulting from the enhancement of sleep slow-waves using auditory
      stimulation. Our objective is to make this concept practical for consumer use by
      developing and validating an electroencephalogram (EEG) closed-loop system to
      deliver auditory stimulation during sleep to enhance slow-waves. APPROACH: The
      system automatically detects slow-wave sleep with 74% sensitivity and 97%
      specificity and optimally delivers stimulation in the form of 50 ms-long tones
      separated by a constant one-second inter-tone interval at a volume that is
      dynamically modulated such that louder tones are delivered when sleep is deeper.
      The system was tested in a study involving 28 participants (18F, 10M; 36.9  +/- 
      7.3 years old; median age: 40 years old) who used the system for ten nights (five
      nights in a sham condition and five in a stimulation condition). Four nights in
      each condition were recorded at-home and the fifth one in-lab. MAIN RESULTS: The
      analysis in two age groups defined by the median age of participants in the study
      shows significant slow wave activity enhancement (+16.1%, p  <  0.01) for the
      younger group and absence of effect on the older group. However, the older group
      received only a fraction (57%) of the stimulation compared to the younger group.
      Changes in sleep architecture and EEG properties due to aging have influenced the
      amount of stimulation. The analysis of the stimulation timing suggests an
      entrainment-like phenomenon where slow-waves align to the stimulation
      periodicity. In addition, enhancement of spindle power in the stimulation
      condition was found. SIGNIFICANCE: We show evidence of the viability of
      delivering auditory stimulation during sleep, at home, to enhance slow wave
      activity. The system ensures the stimulation delivery to be at the right time
      during sleep without causing disturbance.

PMID- 30215605
TI  - Deep compressive autoencoder for action potential compression in large-scale
      neural recording.
AB  - OBJECTIVE: Understanding the coordinated activity underlying brain computations
      requires large-scale, simultaneous recordings from distributed neuronal
      structures at a cellular-level resolution. One major hurdle to design high
      bandwidth, high-precision, large-scale neural interfaces lies in the formidable
      data streams (tens to hundreds of Gbps) that are generated by the recorder chip
      and need to be online transferred to a remote computer. The data rates can
      require hundreds to thousands of I/O pads on the recorder chip and power
      consumption on the order of Watts for data streaming alone. One of the solutions
      is to reduce the bandwidth of neural signals before transmission. APPROACH: We
      developed a deep learning-based compression model to reduce the data rate of
      multichannel action potentials. The proposed compression model is built upon a
      deep compressive autoencoder (CAE) with discrete latent embeddings. The encoder
      network of CAE is equipped with residual transformations to extract
      representative features from spikes, which are mapped into the latent embedding
      space and updated via vector quantization (VQ). The indexes of VQ codebook are
      further entropy coded as the compressed signals. The decoder network reconstructs
      spike waveforms with high quality from the quantized latent embeddings through
      stacked deconvolution. MAIN RESULTS: Extensive experimental results on both
      synthetic and in vivo datasets show that the proposed model consistently
      outperforms conventional methods that utilize hand-crafted features and/or signal
      agnostic transformations and compressive sensing by achieving much higher
      compression ratios (20-500*) and better or comparable reconstruction accuracies.
      Testing results also indicate that CAE is robust against a diverse range of
      imperfections, such as waveform variation and spike misalignment, and has minor
      influence on spike sorting accuracy. Furthermore, we have estimated the hardware
      cost and real-time performance of CAE and shown that it could support thousands
      of recording channels simultaneously without excessive power/heat dissipation.
      SIGNIFICANCE: The proposed model can reduce the required data transmission
      bandwidth in large-scale recording experiments and maintain good signal
      qualities, which will be helpful to design power-efficient and lightweight
      wireless neural interfaces. We have open sourced the code implementation of the
      work at https://github.com/tong-wu-umn/spike-compression-autoencoder.

PMID- 30215603
TI  - YKL40 in sporadic amyotrophic lateral sclerosis: cerebrospinal fluid levels as a
      prognosis marker of disease progression.
AB  - Amyotrophic lateral sclerosis (ALS) has variable clinical course and fatal
      outcome. Since inflammation plays a role in the pathogenesis of ALS, chitinase-3
      like protein 1 or YKL40 has been assessed as putative biomarker of disease
      progression. YKL40 mRNA levels are increased in anterior horn of the spinal cord
      (P=0.004) in sporadic ALS (sALS) cases when compared with age-matched controls.
      These correlate with increased mRNA expression of microglial markers AIF1 and
      CD68 in the spinal cord in sALS (P=0.044 and P=0.000, respectively). YKL40 mRNA
      and protein expression had a tendency to increase in post-mortem frontal cortex
      area 8 (P=0.06 and P=0.08, respectively). Yet YKL40 immunoreactivity is
      restricted to a subpopulation of astrocytes in these regions. YKL40 protein
      levels, as revealed by enzyme-linked immunosorbent assay (ELISA), are
      significantly increased in the CSF in sALS (n=86) compared with age-matched
      controls (n=21) (P=0.045). Higher levels are found in patients with fast
      progression when compared with patients with slow and normal progression (P=0.008
      and P=0.004, respectively), and correlates with ALS-FRS-R slope (P=0.000).
      Additionally, increased protein levels of neurofilament light chain (NF-L) are
      also found in sALS (P=0.000); highest values are found in patients with fast
      progression when compared with cases with slow and normal progression (P=0.005
      and P=0.000, respectively), and also correlate with ALS-FRS-R slope (P=0.000).
      Pearson's correlation test linked positively the increased levels of YKL40 with
      increased NF-L levels (P=0.013). These data point to YKL40 and NF-L protein
      levels in the CSF as a good biomarker combination of disease progression in sALS.

PMID- 30215606
TI  - Discrimination of methylated and nonmethylated region of a colorectal cancer
      related promoter using fluorescence enhancement of gold nanocluster at
      intrastrand of a 9C-loop.
AB  - Among epigenetic modifications of DNA, methylation of cytosine at its carbon 5 is
      the most common mark that is usually associated with gene silencing in human.
      Determining whether a particular DNA molecule is methylated or not, is an
      indispensable task in many epigenetic investigations. Presenting detection
      methods with less labor-intensive and time-consuming procedures has substantial
      value. Here a facile method based on gold nanocluster (AuNCs) fluorescence
      enhancement is presented. Target sequences were selected from Sept9 promoter
      region as its hypermethylation is demonstrated as a reliable biomarker of
      colorectal cancer. DNA probe was complementary to a 25 nucleotide of the target
      region and possessed 9 additional cytosines in the middle to allow the formation
      of AuNCs. Probe-AuNCs strands were first hybridized with methylated and non
      methylated targets separately, and then their fluorescence intensities were
      recorded. Fluorescence intensity was higher with methylated targets than non
      methylated one. Applying silver ions reversed the situation and fluorescence
      intensities of non-methylated DNA got higher than methylated one.

PMID- 30215607
TI  - Multilayer 3D electrodes for neural implants.
AB  - OBJECTIVE: In many applications, multielectrode arrays employed as neural
      implants require a high density and a high number of electrodes to precisely
      record and stimulate the activity of the nervous system while preserving the
      overall size of the array as little as possible. APPROACH: Here we present a
      multilayer and three-dimensional (3D) electrode array, together with its
      manufacturing method, enabling a higher electrode density and a more efficient
      signal transduction with the biological tissue. MAIN RESULTS: The 3D structure of
      the electrode array allows a multilayer placement of the interconnects within a
      flexible substrate, it narrows the probe size per the same number of electrodes,
      and it maintains the electrode contacts at the same level within the tissue. In
      addition, it augments the electrode surface area, leading to a lower
      electrochemical impedance and a higher charge storage capacity. To characterize
      the recordings capabilities of the multilayer 3D electrodes, we measured visually
      evoked cortical potentials in mice and analysed the evolution of the peak
      prominences and latencies according to different light intensities and recording
      depths within the brain. The resulting signal-to-noise ratio is improved compared
      to flat electrodes. Finally, the 3D electrodes have been imaged inside a
      clarified mouse brain using a light-sheet microscope to visualize their integrity
      within the tissue. SIGNIFICANCE: The multilayer 3D electrodes have proved to be a
      valid technology to ensure tissue proximity and higher recording/stimulating
      efficiencies while enabling higher electrode density and reducing the probe size.

PMID- 30215608
TI  - The temporal resolution and single-molecule manipulation of a solid-state
      nanopore by pressure and voltage.
AB  - The translocation of DNA molecules through nanopores has attracted wide interest
      for single-molecule detection. However, the multiple roles of electric fields
      fundamentally constrain the deceleration and motion control of DNA translocation.
      In this paper, we show how a single anchored DNA molecule can be manipulated for
      repeated capture using a transmembrane pressure gradient. Continuously and slowly
      changing the magnitude of the pressure provided two opposite directions for the
      force field inside a nanopore, and we observed an anchored DNA molecule entering
      the nanopore throughout the process from tentative to total entry. The use of
      both voltage and pressure across a nanopore provides an alternative method to
      capture, detect and manipulate a DNA molecule at the single-molecule level.

PMID- 30215609
TI  - Corrigendum to "Effects of trigonal deformation on electronic structure and
      thermoelectric properties of bismuth" [2018 J Phys Condens Matter 30 285504].
AB  - In the mentioned paper [1], the cohesive energy E (eV/atom) as the function of
      the c/a in Table 3 should be corrected as follows.

PMID- 30215610
TI  - Gumpy: a Python toolbox suitable for hybrid brain-computer interfaces.
AB  - OBJECTIVE: The objective of this work is to present gumpy, a new free and open
      source Python toolbox designed for hybrid brain-computer interface (BCI).
      APPROACH: Gumpy provides state-of-the-art algorithms and includes a rich
      selection of signal processing methods that have been employed by the BCI
      community over the last 20 years. In addition, a wide range of classification
      methods that span from classical machine learning algorithms to deep neural
      network models are provided. Gumpy can be used for both EEG and EMG biosignal
      analysis, visualization, real-time streaming and decoding. RESULTS: The usage of
      the toolbox was demonstrated through two different offline example studies,
      namely movement prediction from EEG motor imagery, and the decoding of natural
      grasp movements with the applied finger forces from surface EMG (sEMG) signals.
      Additionally, gumpy was used for real-time control of a robot arm using steady
      state visually evoked potentials (SSVEP) as well as for real-time prosthetic hand
      control using sEMG. Overall, obtained results with the gumpy toolbox are
      comparable or better than previously reported results on the same datasets.
      SIGNIFICANCE: Gumpy is a free and open source software, which allows end-users to
      perform online hybrid BCIs and provides different techniques for processing and
      decoding of EEG and EMG signals. More importantly, the achieved results reveal
      that gumpy's deep learning toolbox can match or outperform the state-of-the-art
      in terms of accuracy. This can therefore enable BCI researchers to develop more
      robust decoding algorithms using novel techniques and hence chart a route ahead
      for new BCI improvements.

PMID- 30215611
TI  - Evaluating nanomedicine with microfluidics.
AB  - Nanomedicines are engineered nanoscale structures that have an extensive range of
      application in the diagnosis and therapy of many diseases. Despite the rapid
      progress in and tremendous potential of nanomedicines, their clinical
      translational process is still slow, owing to the difficulty in understanding,
      evaluating, and predicting their behavior in complex living organisms.
      Microfluidic techniques offer a promising way to resolve these challenges.
      Carefully designed microfluidic chips enable in vivo microenvironment simulation
      and high-throughput analysis, thus providing robust platforms for nanomedicine
      evaluation. Here, we summarize the recent developments and achievements in
      microfluidic methods for nanomedicine evaluation, categorized into four sections
      based on their target systems: single cell, multicellular system, organ, and
      organism levels. Finally, we provide our perspectives on the challenges and
      future directions of microfluidics-based nanomedicine evaluation.

PMID- 30215612
TI  - Different regimes of the Purcell effect in disordered photonic crystals.
AB  - We demonstrate that disorder in photonic crystals could lead to pronounced
      modification of spontaneous emission rate in the frequency region corresponding
      to the photonic band gap (PBG). Depending on the amount of disorder, two
      different regimes of the Purcell effect occurs. We provide statistical analysis
      of Purcell coefficient on the frequency of the emitter and its position within
      the sample. For the moderate disorder, an enhancement of spontaneous emission
      occurs at the edge of PBG due to the modification of properties of the edge
      state. This effect is responsible for recently observed mirrorless lasing in
      photonic crystals at the edge of PBG. When the level of disorder increases, the
      spontaneous emission rate enhances within the PBG due to the appearance of the
      high quality factor states. This effect is likely responsible for a superlinear
      dependence of emissions on pumping observed in synthetic opals.

PMID- 30215613
TI  - Poole-Frenkel emission on functionalized, multilayered-packed reduced graphene
      oxide nanoplatelets.
AB  - The unique electronic, mechanical and optical properties of graphene make it a
      remarkable 2D material, widely explored in a plethora of applications. However,
      graphene zero-bandgap and the production of defect-free pristine graphene in
      large areas still limit some applications. To circumvent these issues, graphene
      derived 2D materials have arisen as attractive candidates for low-dimensional
      systems, which requires a better comprehension of their properties. Here, we
      report a detailed investigation of the conduction mechanisms of two
      functionalized reduced graphene oxides (rGOs) nanoplatelets, named GPAH and GPSS.
      The functionalized rGO nanoplatelets were bottom-up assembled via the layer-by
      layer technique, enabling molecular-level thickness control of nanostructures
      with well-defined composition and structure. For the reported multilayered
      GPAH/GPSS films the charge carriers followed Mott's law, presenting a typical
      conduction behavior of 2D systems described by the Poole-Frenkel model. The
      multilayered GPAH/GPSS nanostructure presented a conductivity of 10-4 S cm-1,
      optical bandgap of ~3.3 eV and a relative dielectric permittivity (epsilon r) of
      6.4. Temperature-dependent I-V measurements indicated a strong variation of
      epsilon r below the critical temperature (T C = 237 K), associated with a high
      dipole reorientation in the formed GPAH/GPSS nanostructure. All these
      characteristics make the GPAH/GPSS nanocomposite attractive for graphene-oriented
      applications, such as electronic devices.

PMID- 30215614
TI  - Effect of abdominal aortic endoprostheses on arterial pulse wave velocity in an
      in vitro abdominal aortic flow model.
AB  - OBJECTIVE: Aortic pulse-wave-velocity (aPWV) is a measure for arterial stiffness,
      which is associated with increased cardiovascular risk. Recent evidence suggests
      aPWV increases after endograft-placement for aortic aneurysms. The aim of this
      study was to investigate the influence of different aortic endoprostheses on aPWV
      and structural stiffness in vitro. APPROACH: Three different abdominal aortic
      endoprostheses (AFX, Endurant II, and Nellix) were implanted in identical
      silicone aneurysm models. One model was left untreated, and another model
      contained an aortic tube graft (Gelweave). The models were placed in an in vitro
      flow set-up that mimics physiological flow. aPWV was measured as the transit time
      of the pressure wave over the flow trajectory of the suprarenal to iliac segment.
      Structural stiffness corrected for lumen diameter was calculated for each model.
      RESULTS: aPWV was significantly lower for the control compared to the AFX,
      Endurant, Nellix and tube graft models (13.00  +/-  1.20, 13.40  +/-  1.17, 18.18
      +/-  1.20, 16.19  +/-  1.25 and 15.41  +/-  0.87 m s-1, respectively (P  < 
      0.05)). Structural stiffness of the AFX model was significant lower compared to
      the control model (4718 N m-1 versus 5115 N m-1 (P  <  0.001), respectively),
      whereas all other models showed higher structural stiffness. SIGNIFICANCE:
      Endograft placement resulted in a higher aPWV compared to a non-treated aortic
      flow model. All models showed increased structural stiffness over the flow
      trajectory compared to the control model, except for the AFX endoprosthesis.
      Future studies in patients treated with an endograft are needed to evaluate the
      current results in vivo.

PMID- 30215615
TI  - Simulating advanced focused ion beam nanomachining: a quantitative comparison of
      simulation and experimental results.
AB  - A simulation study of focused ion beam (FIB) sputtering in SiO2 is presented. The
      basis of this study is an enhanced version of the EnvizION Monte Carlo simulation
      program for FIB processing, which previously was restricted to targets composed
      of a single atom. A Monte Carlo method is presented for the simulation of FIB
      sputtering in SiO2 in three-dimensions, with ion implantation, to elucidate the
      complex dynamics of nanoscale milling of compound targets. This method is applied
      to the simulation of sputtering experiments using both Ne+ and Ga+ ion beams. We
      compare simulations using experimentally derived 'measured' beam profiles for
      each ion species, and 'effective' beam profiles which are chosen to reproduce
      experimental results. Simulations using the 'measured' beam profiles produce vias
      which are narrower than experiments, while the 'effective' beam profiles for both
      Ne+ and Ga+ are significantly wider than the 'measured' profiles. The difference
      between the 'measured' and 'effective' beam profiles is attributed to widening of
      the milling effects of the beam beyond its static dimensions, due to platform
      level artifacts such as vibrations and, possibly, charging. Simulations using the
      'effective' beam profiles are found to accurately reproduce the depths and
      overall shape of experimental FIB sputtered vias in test cases, which vary in ion
      species, beam energy, total dose, and raster parameters. This comparison is the
      most extensive validation of the EnvizION simulation against experiments to date.
      However, the location of implanted ions in simulations is shallower than
      experiments, which is attributed to the fact that implanted species are required
      to find nearest neighbor vacancies and not allowed to occupy interstitial
      positions.

PMID- 30215616
TI  - [Formula: see text] classification for a novel antiferromagnetic topological
      insulating phase in three-dimensional topological Kondo insulator.
AB  - Antiferromagnetic topological insulator (AFTI) is a topological matter that
      breaks time-reversal symmetry. Since its proposal, explorations of AFTI in strong
      correlated systems are still lacking. In this paper, we show for the first time
      that a novel AFTI phase can be realized in three-dimensional topological Kondo
      insulator (TKI). In a wide parameter region, the ground states of TKI undergo a
      second-order transition to antiferromagnetic insulating phases which conserve a
      combined symmetry of time reversal and a lattice translation, allowing us to
      derive a [Formula: see text]-classification formula for these states. By
      calculating the [Formula: see text] index, the antiferromagnetic insulating
      states are classified into AFTI or non-topological antiferromagnetic insulator
      (nAFI) in different parameter regions. On the antiferromagnetic surfaces in AFTI,
      we find topologically protected gapless Dirac cones inside the bulk gap, leading
      to metallic Fermi rings exhibiting helical spin texture with weak spin-momentum
      locking. Depending on model parameters, the magnetic transitions take place
      either between AFTI and strong topological insulator, or between nAFI and weak
      topological insulator. By varying some model parameters, we find a topological
      transition between AFTI and nAFI, driving by closing of bulk gap. Our work may
      account for the pressure-induced magnetism in TKI compound SmB6, and helps to
      explore richer AFTI phases in heavy-fermion systems as well as in other strong
      correlated systems.

PMID- 30215617
TI  - Radiation tolerance of La-doped nanocrystalline steel under heavy-ion irradiation
      at different temperatures.
AB  - Nanostructured materials have great potential for use as structural materials in
      advanced nuclear reactors due to the high density of grain boundaries that can
      serve as sinks to absorb irradiation-induced defects. In the present study, the
      irradiation tolerance of a La-doped nanocrystalline 304 austenitic stainless
      steel (NC-La) with a grain size of about 40 nm was investigated under an
      irradiation of 6 MeV Au ions to 1.5 * 1016 ions cm-2 at 600  degrees C and room
      temperature. Compared to its coarse-grained counterpart, in La-doped
      nanocrystalline steel no visible voids were observed at high-temperature
      irradiation, and no significant difference in extended defects, such as
      irradiation-induced dislocation loops or clusters, were found between irradiated
      and unirradiated areas at room temperature irradiation. Furthermore, the nano
      grain remains stable under irradiation, and no significant grain growth occurs at
      both irradiation temperatures. The excellent irradiation tolerance of the La
      doped nanocrystalline alloys is attributed to the abundant grain boundaries and
      enhanced stability of nano grains induced by the Zener pinning effect and La
      segregation on grain boundaries. This study therefore demonstrates the superior
      irradiation tolerance of the La-doped nanocrystalline steel.

PMID- 30215618
TI  - Synthesis of superhydrophobic surfaces with Wenzel and Cassie-Baxter state:
      experimental evidence and theoretical insight.
AB  - We demonstrate surfactant- and template-free synthesis of superhydrophobic thin
      films by controlling surface morphology. The surface morphology evolution process
      was determined from time-dependent studies. The relationships between the water
      contact angle, sliding angle, water droplet size, and surface microstructures
      were investigated. It is found that structural parameters play an important role
      in determining the adhesion of a droplet on superhydrophobic surfaces and the
      liquid-solid adhesion can be effectively manipulated through tailoring the
      morphology or the size of the microstructures on the surface. We provide a
      theoretical explanation for the Cassie-Baxter state (water rolls) and the Wenzel
      state (sticky surface, water adheres) with droplet size on different
      microstructure surfaces. The new theoretical insight provided in this study
      matches well with experimental results.

PMID- 30215619
TI  - Ultrahigh photoresponsivity MoS2 photodetector with tunable photocurrent
      generation mechanism.
AB  - Photodetectors with two-dimensional (2D) materials on a SiO2/Si substrate have
      been extensively explored. However, these photodetectors often suffer from a
      large gate voltage and relatively low photoresponsivity due to the low efficiency
      light absorption of 2D materials. Here, we develop a MoS2 photodetector based on
      the Al2O3/ITO (indium tin oxide)/SiO2/Si substrate with ultrahigh
      photoresponsivity of 2.7 * 104 A W-1. Most of the incident light is reflected by
      the interface of stacked Al2O3/ITO/SiO2 substrate, which significantly increases
      the light absorption of 2D materials. With the help of thinner and high-kappa
      Al2O3 dielectric, the current ON/OFF ratio could exceed 109 with a gate voltage
      no more than 2 V. Enhanced gate regulation also brings about a relatively high
      mobility of 84 cm2 V-1 s-1 and subthreshold swing of 104 mV dec-1. Additionally,
      two different photocurrent generation mechanisms have also been revealed by
      tuning the gate voltage. The reflection-enhancement substrate assisted MoS2
      photodetector provides a new idea for improving the performance of 2D material
      photodetectors, which can be perfectly combined with other methods.

PMID- 30215620
TI  - Dopamine effects on stress-induced working memory deficits.
AB  - The prefrontal cortex (PFC) plays a critical role in mediating executive
      functions and orchestrating the way in which we think, decide, and behave. Many
      studies have shown that PFC neurons not only play a major role in mediating
      behavioral responses to stress but are also sensitive to stress and undergo
      remodeling following stress exposure. Activation of the hypothalamic-pituitary
      adrenal axis as a result of stress initiates a flood of alterations in prefrontal
      neurotransmitter release. Dopamine (DA) neurotransmission in the PFC is involved
      in the modulation of stress responsiveness. Compelling results show that
      stressful events are associated with increased DA concentrations in the medial
      PFC. Excessive DA-ergic activity in the medial prefrontal cortex following stress
      has a negative impact on working memory and executive functions in rodents,
      monkeys, and humans, making them unable to processing information selectively and
      impairing cognitive function. Therefore, an exact understanding of these
      mechanisms may provide important insights into the pathophysiology of executive
      dysfunction and novel treatment avenues. The present review provides a summary of
      the neuronal circuitry involved in alterations of PFC dopaminergic neurons under
      conditions of stress, and then addresses the interaction of PFC DA with
      glucocorticoids leading to impairment of working memory under conditions of
      stress.

PMID- 30215623
TI  - In-hospital and long-term prognosis in patients after implantation of implantable
      cardioverter-defibrillators and cardiac resynchronization therapy: 10-year
      results of the SILCARD registry.
AB  - Introduction During the last 20 years, there has been a considerable increase in
      the number of implanted implantable cardioverter-defibrillator (ICD) and cardiac
      resynchronization therapy (CRT) devices. However, there have been only single
      reports on clinical events, including rehospitalizations, in the long-term follow
      up. Objectives We analyzed the baseline clinical characteristics, medical
      procedures used, and complications of patients with implantation of an ICD or CRT
      device. Moreover, we analyzed the causes of rehospitalization and the types of
      treatment used in the 12-month follow-up. Patients and methods Out of 1 208 440
      hospitalizations of patients with cardiovascular diseases included in the SILCARD
      registry, hospitalizations with an ICD-9 code for an ICD or CRT device
      implantation between 2006 and 2016 were selected. Results The analysis included
      12 147 patients with an ICD or CRT device. The total number of hospitalizations
      was 14 552. Over the years, a significant increase in the number of implanted
      devices and a higher percentage of CRT defibrillators was observed. Before the
      implantation, approximately 48.2% of patients underwent revascularization. In
      hospital and 12-month mortality rates were 0.4% and 8.1%, respectively.
      Rehospitalizations due to cardiovascular causes were reported for approximately
      40.3% of patients, with a significant reduction in the analyzed period. The most
      frequent cause of rehospitalization was heart failure (51.4%), while stable
      coronary artery disease and acute coronary syndromes constituted approximately
      16% of the causes. In the 12-month follow-up, nearly every tenth patient was
      subjected to coronary angiography. Approximately 5% of patients required
      revascularization. Conclusions The relatively high rates of hospital readmissions
      and their causes indicate the need for a comprehensive care of patients before
      implantation of ICD or CRT devices and after discharge.

PMID- 30215622
TI  - Executive (dys)function after stroke: special considerations for behavioral
      pharmacology.
AB  - Stroke is a worldwide leading cause of death and long-term disability with
      concurrent secondary consequences that are largely comprised of mood dysfunction,
      as well as sensory, motor, and cognitive deficits. This review focuses on the
      cognitive deficits associated with stroke specific to executive dysfunction
      (including decision making, working memory, and cognitive flexibility) in humans,
      nonhuman primates, and additional animal models. Further, we review some of the
      cellular and molecular underpinnings of the individual components of executive
      dysfunction and their neuroanatomical substrates after stroke, with an emphasis
      on the changes that occur during biogenic monoamine neurotransmission. We
      concentrate primarily on changes in the catecholaminergic (dopaminergic and
      noradrenergic) and serotonergic systems at the levels of neurotransmitter
      synthesis, distribution, reuptake, and degradation. We also discuss potential
      secondary stroke-related behavioral deficits (specifically, poststroke depression
      as well as drug-abuse potential and addiction) and their relationship with stroke
      induced deficits in executive function, an especially important consideration
      given that the average age of the human stroke population is decreasing. In the
      final sections, we address pharmacological considerations for the treatment of
      ischemia and the subsequent functional impairment, as well as current limitations
      in the field of stroke and executive function research.

PMID- 30215621
TI  - Executive (dys)function after traumatic brain injury: special considerations for
      behavioral pharmacology.
AB  - Executive function is an umbrella term that includes cognitive processes such as
      decision-making, impulse control, attention, behavioral flexibility, and working
      memory. Each of these processes depends largely upon monoaminergic (dopaminergic,
      serotonergic, and noradrenergic) neurotransmission in the frontal cortex,
      striatum, and hippocampus, among other brain areas. Traumatic brain injury (TBI)
      induces disruptions in monoaminergic signaling along several steps in the
      neurotransmission process - synthesis, distribution, and breakdown - and in turn,
      produces long-lasting deficits in several executive function domains.
      Understanding how TBI alters monoamingeric neurotransmission and executive
      function will advance basic knowledge of the underlying principles that govern
      executive function and potentially further treatment of cognitive deficits
      following such injury. In this review, we examine the influence of TBI on the
      following measures of executive function - impulsivity, behavioral flexibility,
      and working memory. We also describe monoaminergic-systems changes following TBI.
      Given that TBI patients experience alterations in monoaminergic signaling
      following injury, they may represent a unique population with regard to
      pharmacotherapy. We conclude this review by discussing some considerations for
      pharmacotherapy in the field of TBI.

PMID- 30215624
TI  - Undernutrition and associated factors among children aged 6-59 months living in
      slum areas of Gondar city, northwest Ethiopia: a cross-sectional study.
AB  - Background: Many people, especially in developing countries such as Ethiopia, are
      migrating to cities. The majority of these people have settled in slum areas,
      which often have poor sanitation and housing conditions. Therefore, this study
      was conducted to gather evidence on nutritional status and associated factors
      among children aged 6-59 months living in slum areas of Gondar city, northwest
      Ethiopia. Methods: A community-based cross-sectional study was carried out from 3
      to 28 May 2017. A total of 593 children from the slum areas aged 6-59 months were
      included in the study. Bivariable and multivariable logistic regression analyses
      were carried out to identify the independent determinants of stunting and
      wasting. Results: The overall prevalences of stunting and wasting were 42.3% (95%
      CI 38.34, 46.3%) and 7.3% (95% CI 5.3, 9.4%), respectively. Poor wealth status
      (adjusted odds ratio [AOR] =1.79; 95% CI 1.19, 2.70) and age of child 24-35
      months (AOR=2.56; 95% CI 1.32, 4.96), 36-47 months (AOR=2.27; 95% CI 1.14, 4.54)
      and 48-59 months (AOR=2.69; 95% CI 1.35, 5.32) were independently associated with
      stunting. Similarly, presence of a fever in the previous 2 weeks (AOR=2.29; 95%
      CI 1.20, 4.38) and paternal control over resources (AOR=3.66; 95% CI 1.12, 11.04)
      were associated with wasting. Children of uneducated mothers (AOR=3.30; 95% CI
      1.29, 8.46) were also more likely to be wasted. Conclusion: This study
      illustrates that undernutrition is prevalent in the slum areas of Gondar city and
      is a critical public health problem. Therefore, attention should be targeted at
      economically disadvantaged children living in slum areas. In addition, there is a
      need to improve medical awareness of families with young children in these areas
      and increase the health-seeking behavior of these families, primarily by focusing
      on maternal education. Increasing women's decision-making autonomy over household
      resources is also recommended to address the problem.

PMID- 30215629
TI  - TNF inhibitors for psoriasis.
AB  - Tumor necrosis factor (TNF)-alpha has been identified as a key cytokine mediating
      cutaneous inflammation in the pathogenesis of psoriasis. The TNF inhibitors
      (TNFi's) infliximab, adalimumab, and etanercept are efficacious, Food and Drug
      Administration-approved medications for the treatment of moderate-to-severe
      plaque psoriasis. Each drug has a unique pharmacological profile that can have
      therapeutic implications when choosing a particular TNFi for a patient. An
      understanding of these idiosyncrasies can help guide therapeutic decisions for
      patients with psoriasis that also have inflammatory bowel disease, hepatitis C,
      hepatitis B, latent tuberculosis, obesity, cardiovascular disease, and heart
      failure. It can also help when selecting the right treatment for pregnant
      patients, children and adolescents, or those with insurance constraints or
      compliance issues.

PMID- 30215630
TI  - Ustekinumab for the treatment of psoriasis: an evidence update.
AB  - Ustekinumab is an interleukin-12/23 inhibitor used for the treatment of moderate
      to-severe psoriasis. Here, we review new evidence since ustekinumab was licensed
      for relative efficacy in comparison with other biologic therapies from head-to
      head randomized controlled trials and network meta-analyses for the treatment of
      psoriasis. We also review observational data emerging from psoriasis registries
      reporting the effectiveness and safety of ustekinumab. Overall, new evidence
      suggests that ustekinumab has a favorable balance between efficacy/effectiveness,
      safety, and tolerability and should remain a first-line biologic therapy option
      for patients with severe psoriasis at present.

PMID- 30215632
TI  - IL-23 inhibitors for moderate-to-severe psoriasis.
AB  - Since the identification of high levels of interleukin 23 (IL- 23) in psoriasis
      lesional skin, as well as finding that IL-23 was the most important source of the
      p40 subunit shared by IL-12 and IL-23, significant effort has been made in
      identifying potential new drugs that specifically block the unique IL-23 p19
      subunit. At this time, 2 inhibitors of IL-23 p19 have been approved by the United
      States Food and Drug Administration, guselkumab and tildrakizumab. Two other
      agents, risankizumab and mirikizumab, have completed phase 3 and phase 2 of
      development, respectively. Pivotal trials in the development of these agents and
      clinical use of the approved agents are discussed. Thus far, this class of
      medications seems to provide a high level of efficacy, along with infrequent
      dosing and very favorable safety results.

PMID- 30215628
TI  - Using targeted therapies for inflammatory dermatoses.

PMID- 30215633
TI  - Oral small molecules for psoriasis.
AB  - Psoriasis is chronic inflammatory skin condition that imposes a significant
      physical and psychosocial burden on patients. Moderate to severe psoriasis often
      requires systemic treatments, including oral systemic therapies and biologics. An
      addition to the treatment repository for psoriasis is oral small molecules, which
      include apremilast, tofacitinib, and ponesimod. Of these 3 medications, only
      apremilast is currently approved for the treatment of psoriasis. Long-term safety
      data for apremilast suggest that it has a tolerable safety profile and leads to
      significant improvement in patients with psoriasis; however, there are few head
      to-head comparisons with other oral systemic medications. Tofacitinib and
      ponesimod have demonstrated clinical efficacy in treating psoriasis; however,
      further studies are required to understand the benefit-risk profile of these
      medications in psoriasis patients.

PMID- 30215631
TI  - IL-17 inhibitors for psoriasis.
AB  - The role of the Th17/interleukin (IL)-23 pathway has been well elucidated in
      psoriasis. The IL-17 family includes 6 cytokines: IL-17A, IL-17B, IL-17C, IL-17D,
      IL-17E, and IL-17F. Two monoclonal antibodies targeting IL-17A (secukinumab,
      ixekizumab) and one antibody against the IL-17 receptor (brodalumab) have been
      approved for the treatment of moderate-to-severe plaque psoriasis. Clinical
      efficacy, safety, and tolerability of each agent is reviewed.

PMID- 30215634
TI  - Targeted therapies for pediatric psoriasis.
AB  - Children who are recalcitrant to topical therapy for their moderate to severe
      plaque psoriasis and/or highly visible lesions may be candidates for systemic
      therapy. Methotrexate has been the most commonly used systemic agent in children.
      However, at least 25% of patients are now treated with biologics, especially
      tumor necrosis factor-alpha inhibitors, and their use is expanding as their
      availability, demonstrated safety and efficacy, and practitioner experience are
      increasing. In the United States, etanercept is Food and Drug Administration
      approved for ages 6 years and older and ustekinumab for 12 years of age and
      older. In Europe, adalimumab is also approved for pediatric psoriasis for 4 years
      of age and older. While biologics have the advantage of less frequent
      administration, greater and more rapid efficacy than methotrexate, fewer side
      effects, and a less rigorous need for monitoring, their cost is much higher than
      that of methotrexate and other systemic medications, concerns about the
      development of neutralizing antibodies necessitate continuous treatment, and
      their long-term safety profile remains to be determined.

PMID- 30215637
TI  - Novel therapies in the treatment of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common cutaneous condition characterized by epidermal
      barrier disruption, severe skin inflammation, and pruritus. As a result of our
      growing understanding of disease pathogenesis, the therapeutic armamentarium to
      manage AD is rapidly expanding. Moving beyond broadly immunosuppressive agents,
      newer therapies for AD offer more targeted immunomodulation in the forms of
      phosphodiesterase 4 inhibitors, Janus kinase inhibitors, and anticytokine
      monoclonal antibodies. While such therapies are generally considered safer than
      traditional immunosuppressive agents that have been used off label for AD for
      decades, they are not without risk entirely. In some cases, potential side
      effects may be difficult to manage. This review summarizes current views on AD
      pathogenesis and discusses these novel and emerging therapies, including a
      discussion of the mechanisms of action, potential side effects, and limitations
      of current clinical trials for each drug. While the rapid and prolific expansion
      of therapies to treat AD is encouraging, additional studies are needed to
      adequately evaluate the long-term safety, efficacy, and generalizability among
      different age groups and disease subtypes.

PMID- 30215636
TI  - Overview and update on biologic therapy for moderate-to-severe hidradenitis
      suppurativa.
AB  - Hidradenitis suppurativa (HS) is a frequently devastating inflammatory skin
      disorder. Although many treatments have been tried and tested to date, there is
      only one Food and Drug Administration-approved treatment option, adalimumab,
      which is currently indicated for moderateto- severe HS. Our understanding of the
      management of HS with biologic agents and with nonantibiotic and/ or
      antimicrobial systemic therapies continues to evolve. In this article, we
      summarize the existing data on biologics and other small-molecule systemic
      agents, as well as share our personal experiences with the pharmacological
      management of HS in the clinical setting. Continued challenges that limit our
      ability to study and treat this disease effectively include a lack of a
      universally employed scoring system for disease severity, high variability in
      clinical presentation, high cost of off-label therapy, and the scarcity of long
      term studies on treatment response and medication safety.

PMID- 30215635
TI  - Targeted therapies for psoriatic arthritis: an update for the dermatologist.
AB  - Dermatologists are on the front line to identify psoriatic arthritis (PsA) in
      their patients with psoriasis. PsA is a prevalent and underdiagnosed disease with
      potential long-term complications and sequelae for patients. Targeted biologics
      have transformed the landscape of psoriasis and PsA therapy. These medications
      variably treat clinical manifestations of psoriatic disease: skin psoriasis,
      peripheral and axial arthritis, enthesitis, and nail disease. With many new
      medications either on the market or currently being evaluated by the Food and
      Drug Administration, the purpose of this article is to review PsA for the
      dermatologist, to identify the current therapies that are available, and to help
      select which patients may benefit from these medications. Overall, it is
      important to decide therapy for patients based on the active domains of their
      disease, their comorbidities, and the safety profiles of these medications, as
      well as patient preference for route of administration, frequency, and
      tolerability.

PMID- 30215638
TI  - JAK-STAT signaling pathway inhibition: a role for treatment of various
      dermatologic diseases.
AB  - Cutaneous inflammatory conditions such as psoriasis, atopic dermatitis, alopecia
      areata, vitiligo, and connective tissue diseases often remain a challenge to
      treat. Although there is an in-depth understanding of the clinical presentation
      of these diseases, much less is known regarding the pathophysiology. This has
      limited the effective treatment options for patients. A more detailed
      understanding of the pathogenesis of each disease will lead to newer targeted
      medications with less morbidity. Though there are different pathways involved in
      these diseases, the Janus Kinase (JAK)-Signal Transducer and Activator of
      Transcription proteins (STAT) signaling pathway is common to them all. Therefore,
      this review article endeavors to substantiate the immunopathology and clinical
      utility of the JAK inhibitors as treatments for different chronic inflammatory
      diseases of the skin.

PMID- 30215639
TI  - Efficient synthesis of riboflavin-imprinted magnetic nanoparticles by boronate
      affinity-based surface imprinting for the selective recognition of riboflavin.
AB  - Riboflavin (vitamin B2), a cis-diol-containing compound, is an essential vitamin
      for maintaining human health mainly in energy metabolism and is a critical
      component of enzyme cofactors and flavoproteins. Thus, the determination of
      riboflavin in food products is essential in riboflavin-fortified foods. However,
      analysis of riboflavin at natural levels in foods or biological samples is
      difficult because of its very low concentration level and the presence of
      undesirable matrix effects which could interfere with the measuring system. Thus,
      it is essential to develop efficient and selective enrichment approaches for
      riboflavin. Molecularly imprinted polymers can be well used for riboflavin
      extraction and pre-concentration from food samples. In this study, we present
      riboflavin-imprinted magnetic nanoparticles as an ideal sorbent for the selective
      enrichment of riboflavin followed by direct fluorometric determination. The
      riboflavin-imprinted magnetic nanoparticles were prepared according to a newly
      reported strategy, called boronate affinity-based surface initiated imprinting.
      Magnetic nanoparticles and vinylphenylboronic acid were used as supporting
      materials and a functional monomer, respectively. The prepared riboflavin
      imprinted magnetic nanoparticles exhibited several significant advantages, such
      as excellent selectivity, high binding affinity and low binding pH toward
      riboflavin, which made the molecularly imprinted material become an ideal sorbent
      for the selective enrichment of riboflavin. The prepared riboflavin-imprinted
      magnetic nanoparticles were successfully applied to the analysis of riboflavin in
      milk.

PMID- 30215640
TI  - Polymerization-induced polymer aggregation or polymer aggregation-enhanced
      polymerization? A computer simulation study.
AB  - In this study, using dissipative particle dynamics simulations coupled with the
      stochastic reaction model, we investigate the polymerization-induced polymer
      aggregation process and the polymer aggregation-enhanced polymerization process
      in a binary solution, by simply tuning the solubility of the solvent to one
      species of copolymerization. Our simulations indicate that it is a complicated
      interplay of the copolymerization on the formation of aggregates, namely, on one
      hand the polymerization may induce the aggregation of one species; on the other
      hand it has an effect of mixing the two species together. We also find that the
      polymerization process basically follows the first order reaction kinetics. With
      the increase of insolubility of B species in the solution, it continuously
      deviates from the first order reaction kinetics. In the symmetric
      copolymerization system, we find that the dispersity of copolymers monotonically
      decreases with the increase of reaction probability. This counterintuitive result
      can be understood via the comparison of diffusion-controlled kinetics and
      reaction-controlled kinetics. In the asymmetric system, for systems with
      preferential copolymerization, the mass distribution shapes are Gaussian-like
      with certain peaks. For comparison, for systems with preferential
      homopolymerization, the mass distribution shape shows an obviously bimodal form.
      This study helps to better understand the cooperative competition between the
      reaction dynamics and the diffusion dynamics during the preparation of copolymer
      materials, and could act as a guide to better design and improve the
      copolymerization technologies in laboratories and in industry.

PMID- 30215641
TI  - Copper-catalyzed amination of an alpha-C(sp3)-H bond in inactivated ethers to
      synthesize alpha-aminonitriles.
AB  - A copper-catalyzed functionalization of inert cyclic ethers was developed to
      provide alpha-aminonitriles via a cascade oxidation/amination/ring
      opening/cyanation reaction. A series of highly versatile alpha-aminonitriles were
      obtained from primary or secondary anilines, and heterocyclic and aliphatic
      amines with high yields. This process features excellent functional group
      tolerance, a broad substrate scope, and high activity under ambient conditions.

PMID- 30215642
TI  - Optically pure 2-(quinolin-8-yloxy)cyclohexan-1-ol as a practical agent for
      molecular recognition by NMR and fluorescence spectroscopy.
AB  - Optically pure 2-(quinolin-8-yloxy)cyclohexan-1-ol 1, obtained via simple
      chemical and bio-catalytic steps, was used as a chiral solvating agent for
      molecular recognition of the enantiomers of acids. The discrimination of isomers
      was detected by NMR or fluorescence spectroscopy. Isomers of alpha-substituted
      carboxylic acids, phosphoric acids, unprotected amino acids and dipeptides were
      efficiently detected, while the method can be used for quantitative determination
      for practical applications. Analysis of the crystal of (R,R)-1 (R)-mandelic acid
      established a three point supramolecular interaction.

PMID- 30215643
TI  - A rare example of a phosphine as a halogen bond acceptor.
AB  - We report the preparation and characterisation of a cocrystal of
      triphenylphosphine with 1,3,5-trifluoro-2,4,6-triiodobenzene. The structure
      features a rare example of phosphorus acting as a halogen bond acceptor.

PMID- 30215644
TI  - Correction: Two-dimensional nitrides as highly efficient potential candidates for
      CO2 capture and activation.
AB  - Correction for 'Two-dimensional nitrides as highly efficient potential candidates
      for CO2 capture and activation' by Raul Morales-Salvador et al., Phys. Chem.
      Chem. Phys., 2018, 20, 17117-17124.

PMID- 30215645
TI  - Extending the perturbed matrix method beyond the dipolar approximation:
      comparison of different levels of theory.
AB  - Some years ago we developed a theoretical-computational hybrid quantum/classical
      methodology, the Perturbed Matrix Method (PMM), to be used in conjunction with
      molecular dynamics simulations for the investigation of chemical processes in
      complex systems, that proved to be a valuable tool for the simulation of relevant
      experimental observables, e.g., spectroscopic signals, reduction potentials,
      kinetic constants. In typical PMM calculations the quantum sub-part of the
      system, the quantum centre, is embedded into an external perturbing field
      providing a perturbation operator explicitly calculated up to the dipolar terms.
      In this paper we further develop the PMM approach, beyond the dipolar terms in
      the perturbation operator expansion, by including explicitly the quadrupolar
      terms and/or by expanding the perturbation operator on each atom of the quantum
      centre. These different levels of the perturbation operator expansion, providing
      different levels of theory, have been tested by calculating three different
      spectroscopic observables: the spectral signal of liquid water and aqueous
      benzene due to the lowest energy electronic excitation and the infrared amide I
      band of aqueous trans-N-methylacetamide. All the systems tested show that, even
      though the previous PMM level of theory is already capable of reproducing the
      main features of the spectral signal, the higher levels of theory improve the
      quantitative reproduction of the spectral details.

PMID- 30215646
TI  - Graphene oxide-wrapped dipotassium terephthalate hollow microrods for enhanced
      potassium storage.
AB  - Unique graphene oxide-wrapped organic dipotassium terephthalate hollow microrods
      were synthesised using an abundant and renewable organic resource. They exhibit
      enhanced potassium storage compared to bulk K2TP, which can be ascribed to the
      fast K+ ion transfer kinetics, high electronic conductivity and short diffusion
      distance.

PMID- 30215647
TI  - Li-decorated carbon ene-yne as a potential high-capacity hydrogen storage medium.
AB  - Based on comprehensive first-principles calculations, we predict that Li
      decorated carbon ene-yne (CEY) can serve as a reversible and high density
      hydrogen storage medium. The adsorption structures, charge transfer, electronic
      properties and energy storage characteristics of Li-decorated CEY are
      investigated. It is established that Li can bind strongly to sp and sp2
      hybridized CEY without the formation of Li clusters. The strong interaction
      between Li and CEY is attributed to the sp binding C px/py states which hybridize
      heavily with the Li 2s/2p states. After Li decoration, CEY undergoes a transition
      from a semiconductor to a metal. Each Li atom anchors seven H2 molecules with the
      average adsorption energy falling in a suitable range (-0.2 to -0.4 eV per H2).
      The adsorption mechanism of H2 molecules has also been discussed. Two Li atom
      decorated CEY can obtain up to a 9.96 wt% hydrogen storage capacity.

PMID- 30215648
TI  - Light-assisted dynamic titration: from theory to an experimental protocol.
AB  - In order to design a dynamic titration method, we propose a theoretical model
      harnessing the kinetic properties of the complexation of the titrated species
      with a titrating photoswitchable reagent. Forced oscillations of illumination are
      imposed and concentration oscillations of the targeted species are deduced from
      the equations of chemical kinetics. We determine analytical expressions of the
      resonance conditions on the control parameters, angular frequency, mean light
      intensity, and total concentration of the photoswitchable reagent, which optimize
      the out-of-phase amplitude of concentration oscillations. A user-friendly
      protocol of dynamic titration is proposed.

PMID- 30215650
TI  - Lactoferrin-conjugated pH and redox-sensitive polymersomes based on PEG-S-S-PLA
      PCL-OH boost delivery of bacosides to the brain.
AB  - In the present study, engineered lactoferrin (Lf)-conjugated pH and redox
      sensitive polymersomes derived from the triblock copolymer polyethylene glycol-S
      S-polylactic acid-polycaprolactone (PEG-S-S-PLA-PCL-OH) have been used to deliver
      bacosides to the brain. Bacosides are classified as triterpenoid saponins and are
      used in Indian Ayurveda for reversal of amnesia; however, no study has
      extensively demonstrated their efficacy as a nano-formulation in an animal model.
      The polymer was synthesized by ring opening polymerization of lactide and epsilon
      caprolactone. The nanoparticles obtained by nanoprecipitation showed a core-shell
      morphology, with an average size of 110 nm, by transmission electron microscopy
      (TEM). The colloidal stability, hemocompatibility and cytocompatibility of the
      polymersomes proved their biocompatibility. pH and disulfide linkages in the
      polymeric chain accelerated the disintegration of the polymersomes at pH 6.6 and
      at pH 6.6 with glutathione (GSH) in comparison to pH 7.4, supporting their
      degradation behavior. Supermagnetic iron oxide nanoparticles (SPIONs, 74.99 MUg
      mg-1 polymer) encapsulated into the polymersomes demonstrated their uptake in a
      mouse model by MRI. Furthermore, bacosides encapsulated in the polymersomes (10%
      loading) showed significant memory loss reversal in chemically induced amnesic
      mice, supported by the gene expression profiles of Arc, BDNF and CREB as well as
      by histopathology.

PMID- 30215651
TI  - Organocatalytic asymmetric Michael/hemiketalization/acyl transfer reaction of 1,3
      propanediones with (E)-2-(2-nitrovinyl)phenols.
AB  - An organocatalytic asymmetric cascade Michael/hemiketalization/acyl transfer
      reaction between (E)-2-(2-nitrovinyl)phenols and 1,3-propanediones is disclosed.
      A cinchona alkaloid derived bifunctional thiourea catalyst was found to be the
      most effective for this reaction and provided the desired products in moderate to
      good yields with good to high enantioselectivities.

PMID- 30215649
TI  - Applications to water transport systems: general discussion.

PMID- 30215652
TI  - Copper-catalyzed synthesis of 2-aminophenyl benzothiazoles: a novel approach.
AB  - A novel, convenient and efficient protocol for the construction of various 2
      aminophenyl benzothiazoles by domino intra- and intermolecular C-N cross-coupling
      reactions of arylisothioureas with aryl iodides using an inexpensive, air stable
      and readily available copper catalyst is described. The arylisothioureas were
      obtained from thiourea via copper promoted desulfurization followed by
      nucleophilic substitution. In addition, the reactivity of arylhalides and the
      reaction mechanism have also been studied. The protocol features operational
      simplicity and a broad substrate scope.

PMID- 30215653
TI  - Cyclic arylopeptoid oligomers: synthesis and conformational propensities of
      peptide-mimetic aromatic macrocycles.
AB  - Macrocyclic peptide-mimetic molecules are attracting renewed attention and have
      found widespread application in research fields ranging from biochemical science
      to materials science. Herein, we describe the synthesis and structural
      elucidation of cyclo[n]-p-arylopeptoids (classified into cyclic aromatic epsilon
      amino acids) bearing various side chains, namely, C[n]pAP(Rn) (where n inside
      brackets denotes the number of main chain units and R inside parentheses
      represents side chains). We investigate the influence of n and R on the
      macrocyclization efficiency of linear p-arylopeptoid oligomers (n = 3, 4, 5)
      under high-dilution conditions with or without slow addition. The structures of
      the cyclo[4]-p-arylopeptoids (C[4]pAP(Rn)) and their conformational dynamics are
      disclosed on the basis of single-crystal X-ray analyses, viable-temperature (VT)
      1H NMR studies, and density functional theory (DFT) calculations. We found two
      representative conformations (open and closed) of cyclo[4]-p-arylopeptoids
      (C[4]pAP(Rn)) in the solid state and whose preference in the solution state was
      most likely dependent on solvent polarity. We believe that this simple but
      dynamic macrocyclic peptide-mimetic molecular scaffold would be attractive for
      developing new functional molecular tools based on rational molecular design as
      well as molecular library screening strategies.

PMID- 30215654
TI  - The modelling and enhancement of water hydrodynamics: general discussion.

PMID- 30215655
TI  - Structure and function of natural proteins for water transport: general
      discussion.

PMID- 30215657
TI  - Total synthesis of sesterterpenoids.
AB  - Covering: January 2012 to January 2018Sesterterpenoids are a small family of
      terpenes that often possess intriguing biological profiles and complicated
      chemical structures. Their total syntheses are usually remarkably challenging,
      requiring methodological and strategic innovation. In this review, we summarize
      and discuss the total syntheses of sesterterpenoids published during the coverage
      period, and the key chemical transformations are highlighted.

PMID- 30215656
TI  - Metabolic deregulation in prostate cancer.
AB  - INTRODUCTION: The prostate exhibits a unique metabolism that changes during
      initial neoplasia to aggressive prostate cancer (PCa) and metastasis. The study
      of PCa metabolism thus represents a new avenue for diagnostics, particularly
      early diagnosis of aggressive PCa cases. RESULTS: Here, by clustering tissue
      transcriptomics data from The Cancer Genome Atlas (498 PCa patients), we
      identified six metabolic subgroups (C1-C6) of PCa that show distinct disease-free
      survival (DFS) outcomes (p < 0.0001). In particular, we identified at least two
      subgroups (C5 & C3) that exhibit significant poor prognosis (~70% and 30-40%
      relapse within the first 72 months; hazards ratios of 9.4 and 4.4, respectively,
      relative to the best prognosis cluster C4 that showed <20% relapse even by 120
      months). We were able to reproduce the subgroups in several independent datasets
      including B. S. Taylor et al. (2010) data; 215 patients; DFS p = 0.00088) using a
      multinomial regression classifier. The subgroups displayed distinct metabolic
      profiles vis-a-vis normal tissues, measured as 'deregulation' observed for 20
      metabolic pathways (using Pathifier; Y. Drier and E. Domany, 2013). In
      particular, C5 and C3 showed considerable deregulation for pathways involved in
      synthesis and catabolism of complex forms of lipids and carbohydrates, and these
      were exhibited in parallel or in the face of glycolysis, a common form of energy
      production in cancer cells. The subgroups were significantly over-enriched for
      different sets of genetic alterations [BRCA1, MSH2, FOXA1, TP53 (C5), RB1 and
      STK11(C3); and AR (C1); p <= 8.6 * 10-4], suggesting that distinct sets of
      alterations underpinning the PCa subgroups that 'push' the subgroups towards
      their unique metabolic profiles. Finally, applying the classifier to blood
      protein expression profiles from 42 active surveillance (AS) and 65 advanced
      castrate resistant PCa (ACRPC) patients (D. Olmos et al., 2012) assigned 70.77%
      ACPRC and interestingly reassigned 59.52% AS patients to at least one of the poor
      prognosis subgroups with 35.71% to the metabolically active poor-prognosis
      subgroup C3. CONCLUSION: The identification of PCa subgroups displaying distinct
      clinical outcomes solely from metabolic expression profiles of PCa tumours
      reiterates the significant link between deregulated metabolism and PCa outcomes
      (E. Eidelman et al., 2017). On the other hand, the time to biochemical relapse
      (rise in PSA levels) was not indicative of early relapse seen for subgroups C3
      and C5 (these show considerably late BCR compared to C4). Our study thus
      highlights specific processes (elevated lipid and carbohydrate metabolism
      pathways) that could be better indicators than PSA for early diagnosis of
      aggressive PCa. AVAILABILITY: https://maxwellplus.com/research/metabolic
      deregulation-in-prostate-cancer/.

PMID- 30215658
TI  - Unusual strain-dependent thermal conductivity modulation of silver nanoflower
      polyurethane fibers.
AB  - Thermal management of stretchable and wearable electronic devices is an important
      issue in enhancing performance, reliability, and human thermal comfort. Here, we
      constructed a unique experimental setup which investigated the strain-dependent
      thermal conductivity. The thermal conductivity of flower-shaped silver
      nanoparticle (silver nanoflower)-polyurethane (Ag-PU) composite fibers was
      systematically investigated as a function of strain. The strain-dependent
      temperature distribution of the Joule-heated fiber was measured using an infrared
      camera, and the thermal conductivity was obtained from the 1-dimensional
      Fourier's conduction model. There was a monotonic decrease in both lattice and
      electronic thermal conductivity with stretching at 25  degrees C. However, there
      was an initial increase in lattice and total thermal conductivity in the low
      strain region (<10%), when the fiber was stretched at 45  degrees C, although the
      electronic thermal conductivity decreased monotonically. The softening of the
      polymer at increased temperatures enhanced Poisson's ratio. Resultantly, the
      fiber cross-sectional area and radial-direction inter-particle distance between
      silver nanoflowers decreased. This could increase the thermal transport in
      conductive fibers by modulating the interfaces between silver nanoflowers and
      polyurethane. A further stretching decreased the lattice thermal conductivity due
      to the significantly increased axial distance between silver nanoflowers and the
      decreased filler fraction. The weft-knitted fabric also demonstrated an increased
      thermal conductance in the low strain region (<=30%) at 45  degrees C.

PMID- 30215659
TI  - Benzyloxycalix[8]arene: a new valuable support for NHC palladium complexes in C-C
      Suzuki-Miyaura couplings.
AB  - Benzyloxycalix[8]arene supported catalysts bearing N-heterocyclic carbene
      palladium complexes on each subunit were readily synthesized. Intermediates and
      catalysts were fully characterized, allowing for a fine control of their
      structure. X-ray diffraction analysis confirmed the formation of a calix[8]arene
      bearing eight well-defined NHC palladium complexes. The macrocyclic structure of
      calix[8]arenes allowed for a scalable and chromatography-free catalyst synthesis
      under homogeneous conditions, while the catalytic reaction proceeded under
      heterogeneous conditions, just by changing the nature of the solvent. Indeed,
      when used as a suspension in ethanol, a high TON and TOF were obtained through a
      large panel of functionalized brominated substrates in C-C Suzuki-Miyaura
      couplings, with low metal contamination after simple filtration.

PMID- 30215660
TI  - Two one-dimensional arrays of naphthyl and anthryl groups along peptide nanotubes
      prepared from cyclic peptides comprising alpha- and beta-amino acids.
AB  - A novel cyclic hexapeptide composed of l-alpha-naphthylalanine, d-alpha
      anthrylalanine, and four beta-alanines (CP6) is synthesized and its molecular
      assembly into peptide nanotubes (PNTs) and the electronic properties arising from
      one-dimensional arrays of aromatic groups along the PNTs were investigated. CP6
      with a combination of l- and d-alpha-amino acids is designed to self-assemble
      into PNTs with them stacking on top of each other under the constraint of
      maximizing the number of intermolecular hydrogen bonds between the cyclic
      peptides. Upon PNT formation, the respective side chains of l- and d-alpha-amino
      acids are aligned in line along the PNTs. The topological arrangement of the
      anthryl groups being in close proximity in the CP6 PNT is supported by higher
      photo-excited energy transfer, appearance of the induced Cotton effects, and the
      promoted photo-dimerization reaction upon PNT formation. AFM observations reveal
      that PNT bundles with diameters 5-15 nm are dielectric microcrystals having a
      piezoelectric coefficient of 2-6 pC N-1. Kelvin force microscopy observations
      show the generation of surface potentials over 100 mV owing to the one
      dimensional array of the anthryl groups along PNTs. Incorporation of alpha-amino
      acids with opposite chirality into cyclic beta-peptides is therefore an effective
      molecular design for the nano-architecture of PNTs displaying one-dimensional
      arrays of chromophores along PNTs.

PMID- 30215661
TI  - Manipulating the crystal structure of a conjugated polymer for efficient
      sequentially processed organic solar cells.
AB  - Recently, the sequential (Sq) process, which forms nanoscale network structures
      from quasi-solid-state inter-diffusion through swelling and annealing, is
      considered to be one of the most efficient methods for fabricating organic solar
      cells and blend films. Here, we examined the effect of the crystallinity and
      orientation of poly(3-hexylthiophene) (P3HT) molecules on the formation of the
      nanostructure by carrying out a Sq process using various solvents with different
      boiling points. We showed that the moderate crystallinity promoted suitable inter
      diffusion between the donor (P3HT) and acceptor ([6,6]-pentadeuterophenyl C61
      butyric acid methyl ester, PC60BM), and hence was important for achieving high
      performance solar cells using Sq processing. Nanostructure formation by inter
      diffusion was investigated and visualized by taking a combination of grazing
      incidence wide-angle X-ray scattering (GIWAXS) and time-of-flight secondary ion
      mass spectrometry (ToF-SIMS) measurements. In addition, our Sq-processed solar
      cell yielded a device efficiency as high as 3.25%, and was also impressive
      because it was made with an eco-friendly solvent and using a short-duration
      annealing process, in contrast to the conventional BHJ process. The present
      findings provided advanced insight into the Sq process, and we anticipate this
      efficacious sequential process to contribute not only to the development of
      higher-efficiency organic solar cells but also to the fabrication of functional
      blend films.

PMID- 30215662
TI  - Age at maturation, body structure and their relationship with socioeconomic
      factors.
AB  - Introduction: In this study, we aimed to identify the differences in body
      structure between early, average, and late maturing girls, taking into account
      family characteristics assessing socio-economic and living conditions. Methods:
      This study was conducted in the years 2003 and 2013 in Warsaw, Poland and
      comprised 788 girls in the age group of 11-19 years. The data were collected
      using a questionnaire which included parental education and profession, girls'
      date of birth, age at menarche, and lifestyle characteristics. The measurements
      included height; weight; skinfolds on arm, under scapula, and on abdomen; arm
      circumference; and body mass index (BMI). The girls were divided into three
      groups: early, average, and late maturing. To eliminate the age differences, for
      each of the examined somatic variable, a "z" score was calculated. We analysed
      the combined data of both years (2003 and 2013) due to the lack of difference in
      the mean age at menarche. The primary objective of this study was to assess the
      relationship between somatic body structure and socioeconomic and lifestyle
      factors among early, average, and late maturing girls. Results: Early maturing
      girls possessed higher body weight and BMI. In families with only one child, the
      age at menarche was found to be the earliest than in families with more than one
      child. Body weight, BMI, arm circumference, and fatfold thickness was found to be
      reduced in case of girls whose parents had better education and profession than
      their peers. Higher levels of stress were associated with higher body mass,
      greater BMI, arm circumference, and skinfolds in early maturing girls. The
      associations between body structure with physical activity and family was mainly
      correlated with body weight and BMI. Conclusion: Socioeconomic and lifestyle
      factors may be helpful in some levelling of differences in the body structure
      between girls differing in the age at menarche, especially the level of stress
      and the education and profession of parents.

PMID- 30215664
TI  - Mup-knockout mice generated through CRISPR/Cas9-mediated deletion for use in
      urinary protein analysis.

PMID- 30215663
TI  - Associations of Religious Upbringing With Subsequent Health and Well-Being From
      Adolescence to Young Adulthood: An Outcome-Wide Analysis.
AB  - In the present study, we prospectively examined the associations of religious
      involvement in adolescence (including religious service attendance and prayer or
      meditation) with a wide array of psychological well-being, mental health, health
      behavior, physical health, and character strength outcomes in young adulthood.
      Longitudinal data from the Growing Up Today Study were analyzed using generalized
      estimating equations. Sample sizes ranged from 5,681 to 7,458, depending on
      outcome; the mean baseline age was 14.74 years, and there were 8-14 years of
      follow-up (1999 to either 2007, 2010, or 2013). Bonferroni correction was used to
      correct for multiple testing. All models were controlled for sociodemographic
      characteristics, maternal health, and prior values of the outcome variables
      whenever data were available. Compared with no attendance, at least weekly
      attendance of religious services was associated with greater life satisfaction
      and positive affect, a number of character strengths, lower probabilities of
      marijuana use and early sexual initiation, and fewer lifetime sexual partners.
      Analyses of prayer or meditation yielded similar results. Although decisions
      about religion are not shaped principally by health, encouraging service
      attendance and private practices in adolescents who already hold religious
      beliefs may be meaningful avenues of development and support, possibly leading to
      better health and well-being.

PMID- 30215665
TI  - The role of RIP3 in cardiomyocyte necrosis induced by mitochondrial damage of
      myocardial ischemia-reperfusion.
AB  - Myocardial damage caused by myocardial ischemia-reperfusion injury (MIRI) is
      difficult to be alleviated because cardiomyocyte necrosis is an irreversible and
      unregulated death form. Recently, necroptosis, a necrosis form caused by tumor
      necrosis factor-alpha (TNF-alpha) and Fas ligand (FasL), was found to be
      regulated by receptor interacting protein 3 (RIP3) and RIP3-receptor interacting
      protein 1 (RIP1)-mixed lineage kinase domain like protein (MLKL) pathway. But it
      is unclear whether they also play a regulatory role in MIRI-induced necroptosis.
      Our previous results showed that in rat MIRI, RIP3 could translocate and express
      highly in mitochondria. Therefore, it is important to explore proteins that
      interact with RIP3 which was translocated to mitochondria. The aim of this study
      was to explore the role of RIP3 in cardiomyocyte necrosis induced by
      mitochondrial damage of hypoxia/reoxygenation (H/R). Our results showed that H/R
      could cause RIP3-depended mitochondrial fragmentation and necrosis-based death;
      and RIP3-promoted H/R-induced necroptosis in H9c2 cells through increasing
      lactate dehydrogenase release and inhibiting cell viability. This process did not
      require RIP1 or MLKL but dynamin-related protein 1 (Drp1), which was related to
      Drp1 activation, reactive oxygen species elevation, and DeltaPsim decline. This
      study provides novel insights into the role of RIP3 in cardiomyocyte injury
      during H/R. RIP3 may serve as a potential target for the treatment of MIRI.

PMID- 30215666
TI  - Benefits and Pitfalls of Point-of-Care Coagulation Testing for Anticoagulation
      Management: An ACLPS Critical Review.
AB  - Objectives: Point-of-care (POC) testing is generally less precise and has higher
      reagent costs per test than laboratory-based assays. However, POC hemostasis
      testing can offer significant advantages in particular situations: patient
      managed warfarin therapy as well as rapid turnaround time heparin management for
      intraoperative patients. Of note, POC hemostasis testing is generally approved
      for the purposes of anticoagulation monitoring and is inferior to laboratory
      coagulation testing for the diagnosis of congenital or acquired coagulopathy.
      Methods: The frequently used POC coagulation instruments for POC international
      normalized ratio and activated clotting time are reviewed, as well as their
      typical performance relative to central laboratory testing (where available).
      Results: Several cases are discussed that highlight the benefits, as well as
      pitfalls, of POC coagulation testing. Conclusions: POC coagulation testing for
      anticoagulation monitoring offers advantages in particular situations. Clear
      policies and protocols must be developed to guide proper use of POC versus
      central laboratory hemostasis testing.

PMID- 30215667
TI  - Vitamin D and skeletal health during growth: the functional muscle-bone unit.

PMID- 30215668
TI  - bcGST - an interactive bias-correction method to identify over-represented gene
      sets in boutique arrays.
AB  - Motivation: Gene annotation and pathway databases such as Gene Ontology and Kyoto
      Encyclopedia of Genes and Genomes are important tools in Gene Set Test (GST) that
      describe gene biological functions and associated pathways. GST aims to establish
      an association relationship between a gene set of interest and an annotation.
      Importantly, GST tests for over-representation of genes in an annotation term.
      One implicit assumption of GST is that the gene expression platform captures the
      complete or a very large proportion of the genome. However, this assumption is
      neither satisfied for the increasingly popular boutique array nor the custom
      designed gene expression profiling platform. Specifically, conventional GST is no
      longer appropriate due to the gene set selection bias induced during the
      construction of these platforms. Results: We propose bcGST, a bias-corrected Gene
      Set Test by introducing bias correction terms in the contingency table needed for
      calculating the Fisher's Exact Test (FET). The adjustment method works by
      estimating the proportion of genes captured on the array with respect to the
      genome in order to assist filtration of annotation terms that would otherwise be
      falsely included or excluded. We illustrate the practicality of bcGST and its
      stability through multiple differential gene expression analyses in melanoma and
      TCGA cancer studies. Availability: The bcGST method is made available as a Shiny
      web application at http://shiny.maths.usyd.edu.au/bcGST/. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30215670
TI  - Universal Screening of Pregnant Women for Hepatitis C: The Time Is Now.
AB  - The epidemiology of hepatitis C virus (HCV) has changed significantly over the
      last decade. Once most prevalent among older adults, the current burden has
      disproportionately affected young adults including women of childbearing age
      (WOCA). The Society for Maternal-Fetal Medicine recently issued guidelines that
      made no change in the recommendation to screen pregnant women based on risk
      factors. The current burden in young adults including WOCA supports a change in
      strategy away from risk-based screening to universal HCV screening in pregnancy.
      Universal screening offers several advantages that position us for a future where
      HCV treatment in pregnancy can happen and offers us progress toward the
      elimination of HCV.

PMID- 30215669
TI  - Priority Switches in Visual Working Memory are Supported by Frontal Delta and
      Posterior Alpha Interactions.
AB  - Visual working memory (VWM) distinguishes between representations relevant for
      imminent versus future perceptual goals. We investigated how the brain
      sequentially prioritizes visual working memory representations that serve
      consecutive tasks. Observers remembered two targets for a sequence of two visual
      search tasks, thus making one target currently relevant, and the other
      prospectively relevant. We show that during the retention interval prior to the
      first search, lateralized parieto-occipital EEG alpha (8-14 Hz) suppression is
      stronger for current compared with prospective search targets. Crucially, between
      the first and second search task, this difference in posterior alpha
      lateralization reverses, reflecting the change in priority states of the two
      target representations. Connectivity analyses indicate that this switch in
      posterior alpha lateralization is driven by frontal delta/low-theta (2-6 Hz)
      activity. Moreover, this frontal low-frequency signal also predicts task
      performance after the switch. We thus obtained evidence for large-scale network
      interactions underlying the flexible shifting between the priority states of
      multiple memory representations in VWM.

PMID- 30215671
TI  - Increased Metabolic Activity on 18F-Fluorodeoxyglucose Positron Emission
      Tomography-Computed Tomography in Human Immunodeficiency Virus-Associated Immune
      Reconstitution Inflammatory Syndrome.
AB  - Background: Immune reconstitution inflammatory syndrome (IRIS) represents an
      unexpected inflammatory response shortly after initiation of antiretroviral
      therapy (ART) in some human immunodeficiency virus (HIV)-infected patients with
      underlying neoplasia or opportunistic infections, including tuberculosis. We
      hypothesized that IRIS is associated with increased glycolysis and that 18F
      fluorodeoxyglucose (FDG) positron emission tomography-computed tomography
      (PET/CT) could help identify high-risk subjects. Methods: In this prospective
      cohort study, 30 HIV-infected patients (CD4+ count <100 cells/uL) underwent FDG
      PET/CT scans at baseline and 4-8 weeks after ART initiation. Ten patients
      developed IRIS (6 mycobacterial). Results: At baseline, total glycolytic
      activity, total lesion volume, and maximum standardized uptake values (SUVs) of
      pathologic FDG uptake (reflective of opportunistic disease burden) were
      significantly higher in IRIS vs non-IRIS (P = .010, .017, and .029, respectively)
      and significantly correlated with soluble inflammatory biomarkers (interferon
      gamma, myeloperoxidase, tumor necrosis factor, interleukin 6, soluble CD14).
      Baseline bone marrow (BM) and spleen FDG uptake was higher in mycobacterial IRIS
      specifically. After ART initiation, BM and spleen mean SUV decreased in non-IRIS
      (P = .004, .013) but not IRIS subjects. Our results were supported by
      significantly higher glucose transporter 1 (Glut-1) expression of CD4+ cells and
      monocytes after ART initiation in IRIS/mycobacterial IRIS compared with non-IRIS
      patients. Conclusions: We conclude that increased pathologic metabolic activity
      on FDG-PET/CT prior to ART initiation is associated with IRIS development and
      correlates with inflammatory biomarkers. Abnormally elevated BM and spleen
      metabolism is associated with mycobacterial IRIS, HIV viremia, and Glut-1
      expression on CD4+ cells and monocytes. Clinical Trials Registration:
      NCT02147405.

PMID- 30215673
TI  - GenomeFlow: A Comprehensive Graphical Tool for Modeling and Analyzing 3D Genome
      Structure.
AB  - Motivation: Three-dimensional (3D) genome organization plays important functional
      roles in cells. User-friendly tools for reconstructing 3D genome models from
      chromosomal conformation capturing data and analyzing them are needed for the
      study of 3D genome organization. Results: We built a comprehensive graphical tool
      (GenomeFlow) to facilitate the entire process of modeling and analysis of 3D
      genome organization. This process includes the mapping of Hi-C data to one
      dimensional (1D) reference genomes, the generation, normalization and
      visualization of two-dimensional (2D) chromosomal contact maps, the
      reconstruction and the visualization of the 3D models of chromosome and genome,
      the analysis of 3D models, and the integration of these models with functional
      genomics data. This graphical tool is the first of its kind in reconstructing,
      storing, analyzing and annotating 3D genome models. It can reconstruct 3D genome
      models from Hi-C data and visualize them in real-time. This tool also allows
      users to overlay gene annotation, gene expression data and genome methylation
      data on top of 3D genome models. Availability: The source code and user manual:
      https://github.com/jianlin-cheng/GenomeFlow.

PMID- 30215672
TI  - Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing,
      Managing, and Treating Hepatitis C Virus Infection.
AB  - Recognizing the importance of timely guidance regarding the rapidly evolving
      field of hepatitis C management, the American Association for the Study of Liver
      Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed
      a web-based process for the expeditious formulation and dissemination of evidence
      based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance
      website undergoes periodic updates as necessitated by availability of new
      therapeutic agents and/or research data. A major update was released
      electronically in September 2017, prompted primarily by approval of new direct
      acting antiviral agents and expansion of the guidance's scope. This update
      summarizes the latest release of the HCV guidance and focuses on new or amended
      recommendations since the previous September 2015 print publication. The
      recommendations herein were developed by volunteer hepatology and infectious
      disease experts representing AASLD and IDSA and have been peer reviewed and
      approved by each society's governing board.

PMID- 30215675
TI  - ARIADNA: machine learning method for ancient DNA variant discovery.
AB  - Ancient DNA (aDNA) studies often rely on standard methods of mutation calling,
      optimized for high-quality contemporary DNA but not for excessive contamination,
      time- or environment-related damage of aDNA. In the absence of validated datasets
      and despite showing extreme sensitivity to aDNA quality, these methods have been
      used in many published studies, sometimes with additions of arbitrary filters or
      modifications, designed to overcome aDNA degradation and contamination problems.
      The general lack of best practices for aDNA mutation calling may lead to
      inaccurate results. To address these problems, we present ARIADNA (ARtificial
      Intelligence for Ancient DNA), a novel approach based on machine learning
      techniques, using specific aDNA characteristics as features to yield improved
      mutation calls. In our comparisons of variant callers across several ancient
      genomes, ARIADNA consistently detected higher-quality genome variants with fast
      runtimes, while reducing the false positive rate compared with other approaches.

PMID- 30215674
TI  - Commentary on: Gummy Smile Treatment: Proposal for a Novel Corrective Technique
      and a Review of the Literature.

PMID- 30215676
TI  - Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase
      positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX
      study.
AB  - Background: The phase III ALEX study in patients with treatment-naive advanced
      anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer
      (NSCLC), met its primary endpoint of improved progression-free survival (PFS)
      with alectinib versus crizotinib. Here we present detailed central nervous system
      (CNS) efficacy data from ALEX. Patients and methods: Overall, 303 patients aged
      >=18 years underwent 1:1 randomization to receive twice-daily doses of alectinib
      600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at
      baseline and every subsequent 8 weeks. Endpoints (analyzed by subgroup: patients
      with/without baseline CNS metastases; patients with/without prior radiotherapy)
      included: PFS, CNS objective response rate (ORR), and time to CNS progression.
      Results: In total, 122 patients had Independent Review Committee-assessed
      baseline CNS metastases (alectinib, n = 64; crizotinib, n = 58); 43 had
      measurable lesions (alectinib, n = 21; crizotinib, n = 22), and 46 had received
      prior radiotherapy (alectinib, n = 25; crizotinib, n = 21). Investigator-assessed
      PFS with alectinib was consistent between patients with baseline CNS metastases
      [hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25-0.64] and those
      without (HR 0.51, 95% CI: 0.33-0.80, P interaction = 0.36). Similar results were
      seen in patients regardless of prior radiotherapy. Time to CNS progression was
      significantly longer with alectinib versus crizotinib and comparable between
      patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7%
      with alectinib versus 71.4% with crizotinib in patients who received prior
      radiotherapy, and 78.6% versus 40.0%, respectively, in those who had not.
      Conclusion: Alectinib demonstrated superior CNS activity and significantly
      delayed CNS progression versus crizotinib in patients with previously untreated,
      advanced ALK+ NSCLC, irrespective of prior CNS disease or radiotherapy. Clinical
      trial registration: ClinicalTrials.gov NCT02075840.

PMID- 30215677
TI  - Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat
      dosing schedule in patients with cancer.
AB  - Background: A nivolumab monotherapy flat-dosing regimen of 480 mg every 4 weeks
      (Q4W) has been approved in the United States, Canada, and European Union as an
      alternative dosing regimen for several indications. Approvals of this Q4W regimen
      were based on population pharmacokinetic (PK) analyses, established flat exposure
      response relationships, and clinical safety. The objective of this study was to
      compare the PK exposure of 480 mg Q4W with 3 mg/kg every 2 weeks (Q2W) and 240 mg
      Q2W using modeling and simulation, and to evaluate clinical safety of the Q4W
      regimen. Patients and methods: Nivolumab PK exposure for the 480 mg Q4W schedule
      was simulated for 3817 patients across multiple tumor types and compared with
      those for the 3 mg/kg Q2W and 240 mg Q2W schedules. The safety profile of the Q4W
      schedule was assessed by analysis of clinical data from 61 patients who
      transitioned to nivolumab 480 mg Q4W from 3 mg/kg Q2W during four phase III
      clinical trials. Results: Compared with 3 mg/kg Q2W, nivolumab 480 mg Q4W
      produced similar time-averaged concentration, approximately 16% lower trough
      concentration, and 45% higher peak concentration at steady state. The peak
      concentration for 480 mg Q4W was significantly lower than that of 10 mg/kg Q2W, a
      dose previously shown to have an acceptable tolerability and safety profile.
      Treatment-related adverse events (TRAEs) that started after transitioning from 3
      mg/kg Q2W to 480 mg Q4W were reported in 14.8% of patients, with 1.6% of patients
      reporting grade 3-4 TRAEs. Pooled safety data for these patients are consistent
      with those for the 3 mg/kg Q2W schedules, and no new safety signals were
      identified. Conclusions: The time-averaged steady-state exposure and safety
      profile of nivolumab 480 mg Q4W are consistent with that of 3 mg/kg Q2W across
      multiple tumor types. Nivolumab 480 mg Q4W represents a new dosing schedule
      option, and in addition to 240 mg Q2W, provides convenience and flexibility for
      patient care. Clinical trial numbers: NCT01721772, NCT01668784, NCT01673867,
      NCT01642004.

PMID- 30215679
TI  - A Bayesian framework for high-throughput T cell receptor pairing.
AB  - Motivation: The study of T cell receptor repertoires has generated new insights
      into immune system recognition. However, the ability to robustly characterize
      these populations has been limited by technical barriers and an inability to
      reliably infer heterodimeric chain pairings for T cell receptors. Results: Here,
      we describe a novel analytical approach to an emerging immune repertoire
      sequencing method, improving the resolving power of this low-cost technology.
      This method relies upon the distribution of a T cell population across a 96-well
      plate, followed by barcoding and sequencing of relevant portions of each T cell
      genome. Multicell Analytical Deconvolution for High Yield Paired-chain Evaluation
      (MADHYPE) uses Bayesian inference to more accurately extract T cell receptor
      information, improving our ability to study and characterize T cell populations
      for immunology and immunotherapy applications. Availability: The MAD-HYPE
      algorithm is released as an open-source project under the Apache License and is
      available from https://github.com/birnbaumlab/MAD-HYPE. Supplementary
      Information: Supplementary data are available at Bioinformatics online.

PMID- 30215678
TI  - Autism spectrum disorder.
AB  - Sources of data: This article is based on key recent published literature
      including international guidelines and relevant reviews and meta-analyses.
      Authors have also supplemented this material with their own clinical experience.
      Areas of agreement: There is an agreement that autism spectrum disorder (ASD)
      have a strong hereditary component. There is also a consensus that the reported
      prevalence estimates have increased in the last 5 years. There is strong support
      for using the broader spectrum disorder conceptualization of the DSM-5. Areas of
      controversy: Higher public awareness of ASD has generated several controversial
      theories of causation. We review a number of environmental risk factors receiving
      media attention including: vaccines, mercury, heavy metal exposure and Selective
      Serotonin Uptake Inhibitors (SSRIs). Popular yet controversial treatment
      interventions are discussed. Early diagnostic screening tools are also addressed.
      Growing points: There is increasing scientific interest in identifying biomarkers
      of autism with potential for early diagnosis, prognostic indicators and
      predictive treatment responses. We review evidence from genetics, neuroimaging
      and eye tracking as candidate biomarkers. Area timely for developing research:
      Family studies point to a strong hereditary component in the aetiology of autism.
      However these studies have not established 100% concordance rates, suggesting a
      role for environmental factors. The gene-environment interplay has not received
      enough attention in scientific research. This represents an important new avenue
      for research in ASD.

PMID- 30215681
TI  - Quantitative Analysis of Polycyclic Aromatic Hydrocarbons at Part Per Billion
      Levels in Fish Oil by Headspace Solid-Phase Microextraction and Gas
      Chromatography-Mass Spectrometry (HS-SPME-GC-MS).
AB  - Headspace solid-phase microextraction (HS-SPME) was used in combination with gas
      chromatography-mass spectrometry (GC-MS) for the analysis of polycyclic aromatic
      hydrocarbons (PAH) at part per billion levels in fish oil samples collected from
      menhaden fish. The method was initially developed using fish oil from capsules
      spiked with a standard PAH mixture. The final HS-SPME-GC-MS method presented a
      linear range from 3 to 1,500 ng/g, with precision for most analytes <10% relative
      standard deviation. The limits of detection varied from 1 to 7 ng/g depending on
      the analyte. Real sample analysis was done on menhaden fish oil extracted from
      fish collected off the coasts of New Jersey and Louisiana. Naphthalene, fluorene,
      fluoranthene, pyrene, anthracene were detected at low levels of 70-180 ng/g in
      the real samples. The concentrations of PAHs detected in the real samples were
      well below established levels of concern for PAHs in finfish.

PMID- 30215682
TI  - ESCAT: A Step in the Right Direction.

PMID- 30215680
TI  - A Polygenic Score for Higher Educational Attainment is Associated with Larger
      Brains.
AB  - People who score higher on intelligence tests tend to have larger brains. Twin
      studies suggest the same genetic factors influence both brain size and
      intelligence. This has led to the hypothesis that genetics influence intelligence
      partly by contributing to the development of larger brains. We tested this
      hypothesis using four large imaging genetics studies (combined N = 7965) with
      polygenic scores derived from a genome-wide association study (GWAS) of
      educational attainment, a correlate of intelligence. We conducted meta-analysis
      to test associations among participants' genetics, total brain volume (i.e.,
      brain size), and cognitive test performance. Consistent with previous findings,
      participants with higher polygenic scores achieved higher scores on cognitive
      tests, as did participants with larger brains. Participants with higher polygenic
      scores also had larger brains. We found some evidence that brain size partly
      mediated associations between participants' education polygenic scores and their
      cognitive test performance. Effect sizes were larger in the population-based
      samples than in the convenience-based samples. Recruitment and retention of
      population-representative samples should be a priority for neuroscience research.
      Findings suggest promise for studies integrating GWAS discoveries with brain
      imaging to understand neurobiology linking genetics with cognitive performance.

PMID- 30215683
TI  - Many Opportunities to Record, Diagnose, or Treat Injection Drug-related
      Infections Are Missed: A Population-based Cohort Study of Inpatient and Emergency
      Department Settings.
AB  - Background: Injection drug use (IDU) and IDU-related infections have increased
      dramatically. However, the incidence of IDU-related infections may be
      underreported because drug use is not recorded in diagnostic records where
      associated infections are identified. Our goal was to estimate a more accurate
      incidence of IDU-related infections by including IDU-related infections not
      recorded at the time infections are diagnosed. Methods: We performed a
      retrospective cohort study using inpatient and emergency department visits from
      the Healthcare Cost and Utilization Project for California, Florida, and New
      York. We identified all patients diagnosed with bacteremia or sepsis,
      endocarditis, osteomyelitis or septic arthritis, and skin or soft tissue
      infection. We estimated the incidence of IDU-related infections by identifying
      cases where drug use was recorded at the time of an infection and cases where
      drug use was not recorded at the time of infection but within 6 months before or
      after the infection diagnosis. We also analyzed factors associated with
      unrecorded IDU. Results: There has been an increasing trend in the number of IDU
      related infections. The annual number of IDU-related infections increased between
      105% and 218% after incorporating infections in which drug use was unrecorded.
      Factors associated with drug use being unrecorded included emergency department
      diagnosis, the level of hospital experience treating drug use, age <18 years, and
      having Medicare as the primary payer. Conclusions: More than half of all IDU
      related infections may be unrecorded in existing surveillance estimates. There
      may be many missed opportunities to record, diagnose, or treat underlying drug
      abuse among patients presenting with IDU-related infections.

PMID- 30215684
TI  - Reply to the letter to the editor on 'Body mass index and 20-specific cancers-re
      analyses of dose-response meta-analyses of observational studies'. By G.
      Markozannes, I. Kalliala, M. Kyrgiou M and KK Tsilidis.

PMID- 30215685
TI  - Frontoparietal Networks Mediate the Behavioral Impact of Alpha Inhibition in
      Visual Cortex.
AB  - Alpha oscillations are known to play a central role in the functional inhibition
      of visual cortices, but the mechanisms involved are poorly understood. One
      noninvasive method for modulating alpha activity experimentally is through the
      use of flickering visual stimuli that "entrain" visual cortices. Such alpha
      entrainment has been found to compromise visual perception and affect widespread
      cortical regions, but it remains unclear how the interference occurs and whether
      the widespread activity induced by alpha entrainment reflects a compensatory
      mechanism to mitigate the entrainment, or alternatively, a propagated
      interference signal that translates to impaired visual processing. Herein, we
      attempt to address these questions by integrating alpha entrainment into a
      modified Posner cueing paradigm, while measuring the underlying dynamics using
      magnetoencephalography. Our findings indicated that alpha entrainment is
      negatively related to task performance, such that as neural entrainment increases
      on the attended side (relative to the unattended side) accuracy decreases.
      Further, this attentional biasing is found to covary robustly with activity in
      the frontoparietal attention network. Critically, the observed negative
      entrainment effect on task accuracy was also fully mediated by activity in
      frontoparietal regions, signifying a propagation of the interfering alpha
      entrainment signal from bottom-up sensory to top-down regulatory networks.

PMID- 30215687
TI  - MicroRNAs in skeletal muscle aging: Current issues and perspectives.
AB  - Skeletal muscle is one of the major organs responsible for body movements and
      metabolism making up approximately 40% of the total body mass. During aging,
      skeletal muscle exhibits a degenerative age-associated decline in mass and
      function termed sarcopenia. This age-associated dysfunction of skeletal muscle is
      a major criterion of morbidity, mortality, and overall declines of quality of
      life in the elderly. Therefore, researchers have focused on identifying
      modulators of muscle aging process including mRNAs, proteins, and recently small
      non-coding RNAs such as microRNAs (miRNAs). In particular, miRNAs have been
      demonstrated to play a critical role in skeletal muscle development and
      homeostasis. Recent studies revealed that miRNAs were also involved in muscle
      aging processes and the rejuvenation of aged muscle by regulating important
      molecules and pathways of aging including insulin-like growth factors (IGFs), NAD
      (+)-dependent protein deacetylase surtuin 1 (SIRT1), telomerase reverse
      transcriptase (TERT), and transforming growth factor beta (TGF-beta) signaling
      pathway. Over the years, miRNAs have emerged as promising candidates for
      biomarkers of sarcopenia and targets for interventions to slow muscle aging. Here
      we comprehensively review the current knowledge on the role of miRNAs in skeletal
      muscle aging and highlight their potential as biomarkers or therapeutic targets
      for skeletal muscle health.

PMID- 30215686
TI  - Dentate Granule Neurons Generated During Perinatal Life Display Distinct
      Morphological Features Compared With Later-Born Neurons in the Mouse Hippocampus.
AB  - In nonhuman mammals and in particular in rodents, most granule neurons of the
      dentate gyrus (DG) are generated during development and yet little is known about
      their properties compared with adult-born neurons. Although it is generally
      admitted that these populations are morphologically indistinguishable once
      mature, a detailed analysis of developmentally born neurons is lacking. Here, we
      used in vivo electroporation to label dentate granule cells (DGCs) generated in
      mouse embryos (E14.5) or in neonates (P0) and followed their morphological
      development up to 6 months after birth. By comparison with mature retrovirus
      labeled DGCs born at weaning (P21) or young adult (P84) stages, we provide the
      evidence that perinatally born neurons, especially embryonically born cells, are
      morphologically distinct from later-born neurons and are thus easily
      distinguishable. In addition, our data indicate that semilunar and hilar GCs, 2
      populations in ectopic location, are generated during the embryonic and the
      neonatal periods, respectively. Thus, our findings provide new insights into the
      development of the different populations of GCs in the DG and open new questions
      regarding their function in the brain.

PMID- 30215688
TI  - D3-Creatine Dilution to Assess Muscle Mass.

PMID- 30215689
TI  - Initiation of anti-retroviral therapy before pregnancy reduces the risk of
      infection-related hospitalization in HIV-exposed uninfected infants born in a
      high-income country.
AB  - Background: Epidemiological studies conducted in low and high-income countries
      showed that infants exposed to maternal HIV but not infected themselves by the
      virus have a high risk of severe infections. Immune alterations during fetal life
      have been proposed as a possible mechanism. Methods: This prospective study was
      conducted to assess the relative risk of hospitalization for infection in HIV
      exposed uninfected (HEU) infants as compared to HIV-unexposed (HU) infants born
      in a high-income country (HIC). Markers of monocyte activation and levels of
      vaccine and pathogen specific antibodies were measured at birth in maternal and
      cord blood to identify correlates of infant susceptibility. Results: 27 of 132
      HEU infants and 14 of 123 HU infants were hospitalized for infection during the
      first year of life (adjusted HR, 95% CI: 2.33, 1.10-4.97). Most of this increased
      risk was associated with time of initiation of maternal anti-retroviral therapy
      (ART). As compared to HU infants, risk of hospitalization for infection of HEU
      infants was four-fold higher (3.84, 1.69-8.71) when mothers initiated ART during
      pregnancy and was not significantly increased (1.42, 0.58-3.48) when ART was
      initiated before pregnancy. Activation of maternal and newborn monocytes and
      reduced transfer of maternal antibodies were most intense following ART
      initiation during pregnancy and predicted the risk of infant hospitalization.
      Conclusions: These observations indicate that initiation of maternal ART before
      pregnancy reduces the susceptibility of HEU infants born in a HIC to severe
      infections and that this effect could be related to the prevention of immune
      alterations during fetal life.

PMID- 30215690
TI  - Insulin-like growth factor-I receptor and thyroid-associated ophthalmopathy.
AB  - Thyroid-associated ophthalmopathy (TAO) is a complex disease process presumed to
      emerge from autoimmunity occurring in the thyroid gland, most frequently in
      Graves' disease (GD). It is disfiguring and potentially blinding, culminating in
      orbital tissue remodeling and disruption of function of structures adjacent to
      the eye. There are currently no medical therapies proven capable of altering the
      clinical outcome of TAO in randomized, placebo-controlled multicenter trials. The
      orbital fibroblast represents the central target for immune reactivity. Recent
      identification of fibroblasts that originate in the bone marrow as monocyte
      progenitors provides a plausible explanation for why antigens, the expressions of
      which were once considered restricted to the thyroid, are detected in the TAO
      orbit. These cells, known as fibrocytes, express relatively high levels of
      functional thyrotropin receptor (TSHR) through which they can be activated by TSH
      and the GD-specific pathogenic antibodies that underpin thyroid over-activity.
      Fibrocytes also express insulin-like growth factor-I receptor (IGF-IR) with which
      TSHR forms a physical and functional signaling complex. Notably, inhibiting IGF
      IR activity results in the attenuation of signaling initiated at either receptor.
      Some studies suggest that IGF-IR-activating antibodies are generated in GD while
      others refute this concept. These observations served as the rationale for
      implementing a recently completed therapeutic trial of teprotumumab, a monoclonal
      inhibitory antibody targeting IGF-IR in TAO. Results of that trial in active,
      moderate to severe disease revealed dramatic and rapid reductions in disease
      activity and severity. Targeting IGF-IR with specific biologic agents may
      represent a paradigm shift in the therapy of TAO.

PMID- 30215692
TI  - A Global Survey of Gastroenterologists' Travel Advice to Patients with
      Inflammatory Bowel Disease on Immunosuppressive Agents and Management of Those
      Visiting Tuberculosis-Endemic Areas.
AB  - Background: With increasing use of biological therapies and immunosuppressive
      agents, patients with inflammatory bowel disease[IBD] have improved clinical
      outcome and international travel in this group is becoming common. Adequate pre
      travel advice is important. We aim to determine the proportion of
      gastroenterologists who provided pre-travel advice, and to assess their
      management strategies for patients on biological therapies visiting
      tuberculosis[TB]-endemic areas. Methods: A 57-question survey was distributed to
      IBD physicians in 23 countries. We collected physicians' demographics, and using
      a standardized Likert scale, assessed physicians' agreement with stated treatment
      choices. Results: A total of 305 gastroenterologists met inclusion criteria.
      Overall, 52% would discuss travel-related issues: travellers' diarrhoea [TD],
      travel-specific vaccines, medical care and health insurance abroad, and TB. They
      were more likely to advise patients not to travel to TB-endemic area if on both
      anti-tumour necrosis factor [TNF] and azathioprine, than if on vedolizumab and
      azathioprine [47% vs 17.6%, p < 0.01]. More IBD physicians agreed with
      vedolizumab monotherapy vs anti-TNF monotherapy [29.9% vs 23%, p < 0.01]. Two
      thirds would continue all IBD treatments and not cease any medications. Chest X
      ray and interferon-gamma-release assay were the preferred methods to assess for
      active and latent TB infection. Knowledge on vaccines among IBD physicians was
      inadequate (survey mean [SD] scores 10.76 [+/-6.8]). However, they were more
      familiar with the societal guidelines on management of venous thromboembolism and
      TD (mean scores 14.9 [+/-5.3] and 11.9 [+/-3.9] respectively). Conclusion: Half
      of IBD specialists would provide pre-travel advice to IBD patients and two-thirds
      would advise continuing all IBD medications even when travelling to TB-endemic
      areas. More education on vaccinations would be particularly helpful for IBD
      physicians.

PMID- 30215691
TI  - Glucose-Induced beta-Cell Dysfunction In Vivo: Evidence for a Causal Role of C
      jun N-terminal Kinase Pathway.
AB  - Prolonged elevation of glucose can adversely affect beta-cell function. Oxidative
      stress, which has been implicated in glucose-induced beta-cell dysfunction, can
      activate c-jun N-terminal kinase (JNK). However, whether JNK is causal in glucose
      induced beta-cell dysfunction in vivo is unclear. Therefore, we aimed at
      investigating the causal role of JNK activation in in vivo models of glucose
      induced beta-cell dysfunction. Glucose-induced beta-cell dysfunction was
      investigated in the presence or absence of JNK inhibition. JNK inhibition was
      achieved using either (i) the JNK-specific inhibitor SP600125 or (ii) JNK-1-null
      mice. (i) Rats or mice were infused intravenously with saline or glucose with or
      without SP600125. (ii) JNK-1 null mice and their littermate wild-type controls
      were infused intravenously with saline or glucose. Following the glucose infusion
      periods in rats and mice, beta-cell function was assessed in isolated islets or
      in vivo using hyperglycemic clamps. Forty-eight-hour hyperglycemia at ~20 mM in
      rats or 96-hour hyperglycemia at ~13 mM in mice impaired beta-cell function in
      isolated islets and in vivo. Inhibition of JNK using either SP600125 or JNK-1
      null mice prevented glucose-induced beta-cell dysfunction in isolated islets and
      in vivo. Islets of JNK-1-null mice exposed to hyperglycemia in vivo showed an
      increase in Pdx-1 and insulin 2 mRNA, whereas islets of wild-type mice did not.
      Together, these data show that JNK pathway is involved in glucose-induced beta
      cell dysfunction in vivo and is thus a potential therapeutic target for type 2
      diabetes.

PMID- 30215693
TI  - Inhibitory Neuron Activity Contributions to Hemodynamic Responses and Metabolic
      Load Examined Using an Inhibitory Optogenetic Mouse Model.
AB  - Hemodynamic signals are routinely used to noninvasively assess brain function in
      humans and animals. This work examined the contribution of inhibitory neuron
      activity on hemodynamic responses captured by changes in blood flow, volume and
      oxygenation in the cortex of lightly anesthetized mice. Because cortical activity
      is not commonly initiated by inhibitory neurons, experiments were conducted to
      examine the neuronal activity properties elicited by photo-stimulation. We
      observed comparable increases in neuronal activity evoked by forelimb and photo
      stimulation; however, significantly larger increases in blood flow and volume
      were produced by photo-stimulation of inhibitory neurons compared with forelimb
      stimulation. Following blockade of glutamate and GABA-A receptors to reduce
      postsynaptic activity contributions, neuronal activity was reliably modulated and
      hemodynamic changes persisted, though slightly reduced. More importantly, photo
      stimulation-evoked changes in blood flow and volume were suppressed by 75-80%
      with the administration of a nitric oxide synthase inhibitor, suggesting that
      inhibitory neurons regulate blood flow mostly via nitric oxide. Lastly, forelimb
      and photo-stimulation of excitatory neurons produced local decreases in blood
      oxygenation, while large increases were generated by photo-stimulation of
      inhibitory neurons. Estimates of oxygen metabolism suggest that inhibitory neuron
      activity has a small impact on tissue metabolic load, indicating a mismatch
      between the metabolic demand and blood flow regulation properties of inhibitory
      and excitatory neurons.

PMID- 30215695
TI  - Aortic stenosis exacerbates flow aberrations related to the bicuspid aortic valve
      fusion pattern and the aortopathy phenotype.
AB  - OBJECTIVES: A bicuspid aortic valve (BAV) is characterized by variable phenotypic
      manifestations, as well as longitudinal evolution of valve dysfunction and
      ascending aorta dilatation. The present study investigated the impact of severe
      aortic stenosis (AS) on the flow patterns and wall shear stress (WSS)
      distribution in BAV patients with right-left (RL) and right-non-coronary (RN)
      cusp fusion types, and the study aimed to reveal whether aortic dysfunction could
      further alter intrinsic aortic haemodynamic aberrations generated by abnormal BAV
      cusp fusion patterns. METHODS: Four-dimensional flow magnetic resonance imaging
      was performed in 120 BAV subjects and 20 tricuspid aortic valve controls. BAV
      patients were evenly categorized into 4 cohorts, including RL and RN BAV with no
      more than mild aortic dysfunction as well as RL and RN BAV-AS with isolated
      severe AS. RESULTS: BAV subjects exhibited eccentric outflow jets resulting in
      regional WSS elevation at the right-anterior position of the ascending aorta in
      the RL group and the right-posterior location in the RN group (P < 0.005). The
      presence of severe AS resulted in accelerated outflow jets and more prominent
      flow and WSS eccentricity (P < 0.005) by marked helical (P = 0.014) and vortical
      flow formation (P < 0.005), as well as increased prevalence of tubular and
      transverse arch dilatation. The changes to the flow jet in BAV-AS subjects
      blurred the differences in peak flow velocity and WSS distribution between RL and
      RN BAV. Differences in the phenotypes of aortopathy were associated with changes
      in functional haemodynamic parameters such as flow displacement and WSS
      eccentricity. CONCLUSIONS: Severe AS markedly exacerbated aortic flow aberrations
      in BAV patients and masked the existing distinct flow features deriving from RL
      and RN fusion types. Longitudinal studies are needed to investigate the evolution
      of ascending aortic dilatation relative to the interaction between intrinsic cusp
      fusion types and acquired severe valve dysfunction.

PMID- 30215696
TI  - Melatonin as a Hormone: New Physiological and Clinical Insights.
AB  - Melatonin is a ubiquitous molecule present in almost every live being from
      bacteria to humans. In vertebrates, besides being produced in peripheral tissues
      and acting as an autocrine and paracrine signal, melatonin is centrally
      synthetized by a neuroendocrine organ, the pineal gland. Independently of the
      considered species, pineal hormone melatonin is always produced during the night
      and its production and secretory episode duration are directly dependent on the
      length of the night. As its production is tightly linked to the light/dark cycle,
      melatonin main hormonal systemic integrative action is to coordinate behavioral
      and physiological adaptations to the environmental geophysical day and season.
      The circadian signal is dependent on its daily production regularity, on the
      contrast between day and night concentrations, and on specially developed ways of
      action. During its daily secretory episode, melatonin coordinates the night
      adaptive physiology through immediate effects and primes the day adaptive
      responses through prospective effects that will only appear at daytime, when
      melatonin is absent. Similarly, the annual history of the daily melatonin
      secretory episode duration primes the central nervous/endocrine system to the
      seasons to come. Remarkably, maternal melatonin programs the fetuses' behavior
      and physiology to cope with the environmental light/dark cycle and season after
      birth. These unique ways of action turn melatonin into a biological time-domain
      acting molecule. The present review focuses on the above considerations, proposes
      a putative classification of clinical melatonin dysfunctions, and discusses
      general guidelines to the therapeutic use of melatonin.

PMID- 30215694
TI  - Modulation of Feeding and Associated Behaviors by Lateral Hypothalamic Circuits.
AB  - Our ability to modulate and observe neuronal activity in defined neurons in
      freely moving animals has revolutionized neuroscience research in recent years.
      Findings in the lateral hypothalamus (LHA) highlighted the existence of many
      neuronal circuits that regulate distinct phenotypes of feeding behavior,
      emotional valence, and locomotor activity. Several of these neuronal circuits do
      not fit into a common model of neuronal integration and highlight the need to
      improve working models for complex behaviors. This review will specifically focus
      on recent literature that distinguishes LHA circuits based on their molecular and
      anatomical characteristics and studies their role in feeding, associated
      behaviors (e.g., arousal and locomotion), and emotional states (e.g., emotional
      valences).

PMID- 30215697
TI  - Effects of Androgens on the Amyloid-beta Protein in Alzheimer's Disease.
AB  - Age-related androgen depletion has been implicated in compromised neuroprotection
      and is involved in the pathogenesis of neurodegenerative disease, including
      Alzheimer's disease (AD), the leading cause of dementia. Emerging data revealed
      that reduction of both serum and brain androgen levels in males is associated
      with increased amyloid-beta (Abeta) accumulation, a putative cause of AD. It has
      been demonstrated that androgens can function as the endogenous negative
      regulators of Abeta. However, the mechanisms by which androgens regulate Abeta
      production, degradation, and clearance, as well as the Abeta-induced pathological
      process in AD, are still elusive. This review emphasizes the contributions of
      androgen to Abeta metabolism and toxicity in AD and thus may provide novel
      strategies for prevention and therapeutics.

PMID- 30215700
TI  - Get Out the Vote: Social Work and the Midterm Elections.

PMID- 30215699
TI  - VAMP7 Regulates Autophagosome Formation by Supporting Atg9a Functions in
      Pancreatic beta-Cells From Male Mice.
AB  - Dysfunctional mitochondria are observed in beta-cells of diabetic patients, which
      are eventually removed by autophagy. Vesicle-associated membrane protein (VAMP)7,
      a vesicular SNARE protein, regulates autophagosome formation to maintain
      mitochondrial homeostasis and control insulin secretion in pancreatic beta-cells.
      However, its molecular mechanism is largely unknown. In this study, we
      investigated the molecular mechanism of VAMP7-dependent autophagosome formation
      using VAMP7-deficient beta-cells and beta-cell-derived Min6 cells. VAMP7
      localized in autophagy-related (Atg)9a-resident vesicles of recycling endosomes
      (REs), which contributed to autophagosome formation, and it interacted with Hrb,
      Syntaxin16, and SNAP-47. Hrb recruited VAMP7 and Atg9a from the plasma membrane
      to REs. Syntaxin16 and SNAP-47 mediated autophagosome formation at a step later
      than the proper localization of VAMP7 to Atg9a-resident vesicles. Knockdown of
      Hrb, Syntaxin16, and SNAP-47 resulted in defective autophagosome formation,
      accumulation of dysfunctional mitochondria, and impairment of glucose-stimulated
      insulin secretion. Our data indicate that VAMP7 and Atg9a are initially recruited
      to REs to organize VAMP7 and Atg9a-resident vesicles in an Hrb-dependent manner.
      Additionally, VAMP7 forms a SNARE complex with Syntaxin16 and SNAP-47, which may
      cause fusions of Atg9a-resident vesicles during autophagosome formation. Thus,
      VAMP7 participates in autophagosome formation by supporting Atg9a functions that
      contribute to maintenance of mitochondrial quality.

PMID- 30215701
TI  - Transforming primary care-the way forward with the TEAMS2 approach.

PMID- 30215702
TI  - Insight into the specificity and severity of pathogenic mechanisms associated
      with missense mutations through experimental and structural perturbation
      analyses.
AB  - Most pathogenic missense mutations cause specific molecular phenotypes through
      protein destabilization. However, how protein destabilization is manifested as a
      given molecular phenotype is not well understood. We develop here a structural
      and energetic approach to describe mutational effects on specific traits such as
      function, regulation, stability, subcellular targeting or aggregation propensity.
      This approach is tested using large-scale experimental and structural
      perturbation analyses in over thirty mutations in three different proteins
      (cancer-associated NQO1, TTR related with amyloidosis and AGT linked to primary
      hyperoxaluria type I) and comprising five very common pathogenic mechanisms (loss
      of-function and gain-of-toxic function aggregation, enzyme inactivation, protein
      mistargeting and accelerated degradation). Our results revealed that the
      magnitude of destabilizing effects, and particularly, their propagation through
      the structure to promote disease-associated conformational states largely
      determine the severity and molecular mechanisms of disease-associated missense
      mutations. Modulation of the structural perturbation at a mutated site is also
      shown to cause switches between different molecular phenotypes. When very common
      disease-associated missense mutations were investigated, we also found that they
      were not among the most deleterious possible missense mutations at those sites,
      and required additional contributions from codon bias and effects of CpG sites to
      explain their high frequency in patients. Our work sheds light on the molecular
      basis of pathogenic mechanisms and genotype-phenotype relationships, with
      implications for discriminating between pathogenic and neutral changes within
      human genome variability from whole genome sequencing studies.

PMID- 30215703
TI  - Caregiving Status and Health of Heterosexual, Sexual Minority, and Transgender
      Adults: Results From Select U.S. Regions in the Behavioral Risk Factor
      Surveillance System 2015 and 2016.
AB  - Background and Objectives: Insufficient research attention has been paid to the
      diversity of informal caregivers, including sexual and gender minority
      caregivers. This study examined health effects of caregiving separately from
      sexual orientation or gender identity status, while stratifying by gender among
      cisgender adults. We hypothesized that compared with heterosexual cisgender
      noncaregivers, heterosexual caregivers and lesbian/gay/bisexual (LGB), and
      transgender (T) noncaregivers would report poorer health outcomes (i.e., self
      reported health, and poor mental health days and poor physical health days), and
      LGBT caregivers would report the worst health outcomes. Research Design and
      Methods: This is a secondary data analysis of the 2015 and 2016 Behavioral Risk
      Factor Surveillance System data from 19 U.S. states. Results: After adjusting for
      covariates and stratifying by gender among the cisgender sample, heterosexual
      caregivers, LGB noncaregivers and LGB caregivers had significantly higher odds of
      self-reported fair or poor health (adjusted odds ratios [aORs] 1.3-2.0 for women
      and 1.2 for men), poor physical health days (aORs 1.2-2.8 for women and 1.3-2.8
      for men), and poor mental health days (aORs 1.4-4.7 for women and 1.5-5.6 for
      men) compared with heterosexual noncaregivers (reference group). By contrast,
      transgender caregivers did not have significantly poorer health than cisgender
      noncaregivers. Discussion and Implications: LGB caregivers reported the worst
      health compared with other groups on multiple measures, signifying they are an at
      risk population. These results suggest the necessity to develop LGB appropriate
      services and programs to prevent poor health in LGB caregivers. Existing policies
      should also be inclusive of LGBT individuals who are caregivers.

PMID- 30215704
TI  - Treatment of missing maxillary lateral incisors: a clinical and aesthetic
      evaluation.
AB  - Objective: The aim of this study was to evaluate whether implant therapy or
      orthodontic space closure was the best treatment option for patients with missing
      maxillary lateral incisors. Subjects and methods: The implant group (I group)
      consisted of 22 patients aged <26 years who had one or both maxillary lateral
      incisors substituted by a single implant-supported crown. The space-closure group
      (SC group) consisted of patients matched with I group patients based on
      diagnosis, gender, and number. Examinations were performed by one examiner and
      occurred at least 5 years after the prosthetic therapy or orthodontic treatment
      was finished. Clinical examination of the 44 patients involved assessing the
      aesthetics and gingival conditions of the implant-supported crown and the
      replacement canine, the occlusal morphology and the extraoral characteristics.
      Both the patient and examiner answered a question about their satisfaction with
      the aesthetic result. Results: Of the 12 variables analysed by the examiner, one
      variable was significantly improved in the I group and five variables were
      improved in the SC group. There were no significant differences between the
      treatment groups for the remaining six variables. Gingival colour and crown
      length were better in the SC group, and crown colour was better in the I group.
      There were no significant differences between the groups with regards to the
      patient's and examiner's overall aesthetic satisfaction of the maxillary anterior
      teeth or between the patient's and examiner's opinion. Conclusion: If both
      treatment alternatives are available, space closure is preferable.

PMID- 30215705
TI  - Motivational Enhancement Therapy for Veterans with Chronic Pain and Substance
      Use.

PMID- 30215706
TI  - Can Activity Monitors Predict Outcomes in Patients with Heart Failure? A
      Systematic Review.
AB  - Background: Actigraphy is increasingly incorporated into clinical practice to
      monitor intervention effectiveness and patient health in congestive heart failure
      (CHF). We explored the prognostic impact of actigraphy-quantified physical
      activity (AQPA) on CHF outcomes. Methods: PubMed and Medline databases were
      systematically searched for cross-sectional studies, cohort studies or randomised
      controlled trials from January 2007 to December 2017. We included studies that
      used validated actigraphs to predict outcomes in adult HF patients. Study
      selection and data extraction were performed by two independent reviewers.
      Results: A total of 17 studies (15 cohort, 1 cross-sectional, 1 randomised
      controlled trial) were included, reporting on 2,759 CHF patients (22-89 years,
      27.7% female). Overall, AQPA showed a strong inverse relationship with mortality
      and predictive utility when combined with established risk scores, and prognostic
      roles in morbidity, predicting cognitive function, New York Heart Association
      functional class and intercurrent events (e.g. hospitalisation), but weak
      relationships with health-related quality of life scores. Studies lacked
      consensus regarding device choice, time points and thresholds of PA measurement,
      which rendered quantitative comparisons between studies difficult. Funding: No
      specific funding was provided for this review. Conclusions: AQPA has a strong
      prognostic role in CHF. Multiple sampling time points would allow calculation of
      AQPA changes for incorporation into risk models. Consensus is needed regarding
      device choice and AQPA thresholds, while data management strategies are required
      to fully utilise generated data. Big data and machine learning strategies will
      potentially yield better predictive value of AQPA in CHF patients. Registration:
      Nil.

PMID- 30215698
TI  - Diabetes, Obesity, and Breast Cancer.
AB  - The rates of obesity and diabetes are increasing worldwide, whereas the age of
      onset for both obesity and diabetes are decreasing steadily. Obesity and diabetes
      are associated with multiple factors that contribute to the increased risk of a
      number of different cancers, including breast cancer. These factors are
      hyperinsulinemia, elevated IGFs, hyperglycemia, dyslipidemia, adipokines,
      inflammatory cytokines, and the gut microbiome. In this review, we discuss the
      current understanding of the complex signaling pathways underlying these multiple
      factors involved in the obesity/diabetes-breast cancer link, with a focus
      particularly on the roles of the insulin/IGF system and dyslipidemia in
      preclinical breast cancer models. We review some of the therapeutic strategies to
      target these metabolic derangements in cancer. Future research directions and
      potential therapeutic strategies are also discussed.

PMID- 30215707
TI  - The availability, price and affordability of antidiabetic drugs in Hubei
      province, China.
AB  - Based on the high prevalence and undiagnosed rate of diabetes mellitus in China
      in recent years, the aim of this work was to evaluate the availability, price and
      affordability of pharmacotherapy for diabetes in public hospitals in Hubei
      province, China. In 2016, a cross-sectional survey was conducted using World
      Health Organization/Health Action International (WHO/HAI) methodology.
      Information on the availability and prices of 20 antidiabetic drugs was collected
      from 34 public hospitals representing three levels of care. Of the 20
      antidiabetic drugs, 70.6% were below 50% availability. Total availability of the
      20 drugs was higher in secondary and tertiary hospitals than in primary
      hospitals. All three hospital levels had higher availability of essential than
      non-essential antidiabetic medicines. The median markup ratios of originator
      brands (OBs) and lowest-price generics (LPGs) were 15.6% and 2.1%, respectively.
      The median potential saving ratio of using generics was 31.3%. Overall, the
      median affordability of 31 antidiabetic drugs ranged from 1.2 to 8.5 days of
      disposable income for residents with three income levels. After insurance
      reimbursement, the increase in the proportion of affordable drugs in urban and
      rural areas averaged 35.5% and 12.9%, respectively. The proportion of drugs with
      low availability and low affordability dropped from 54.8% to 38.7%. However,
      41.7% of urban diabetic patients and 74.0% of rural diabetic patients remained
      unable to afford the drugs surveyed. Higher income and generic substitution are
      factors facilitating affordability. In Hubei province, the overall availability
      of 20 antidiabetic drugs was low, especially in primary hospitals. The
      affordability of most drugs surveyed was also low. Current health insurance can
      greatly improve affordability for urban residents with middle or high income.
      Policy changes should focus on the supply, pricing and clinical use of
      antidiabetic drugs and special health insurance plan for low income population
      with diabetes.

PMID- 30215708
TI  - Association of facial sagittal and vertical characteristics with facial
      aesthetics in the Northern Finland Birth Cohort 1966.
AB  - Objective: To explore the association of facial sagittal and vertical dimensions
      with aesthetic assessment by three panel groups. Materials and methods: The study
      population comprised adult individuals from the Northern Finland Birth Cohort
      1966 (NFBC1966). A clinical oral examination including digital facial photographs
      was performed. The study population was divided into subjects with the lowest and
      highest values in soft tissue measurements in lower anterior facial height
      percentage (LAFH%) (60 subjects) and antero-posterior jaw relationship [soft
      tissue A-point, nasion, and B-point (ANB) angle; 60 subjects] and a control group
      (30 subjects). Frontal and profile facial photographs were presented to three
      panel groups: five orthodontists, five dentists, and five laypersons, who
      evaluated the photographs using the visual analogue scale (VAS). Results: This
      study showed significant differences in VAS mean scores between the panel groups.
      Curve estimation revealed a significant quadratic association between aesthetic
      VAS evaluation and ANB angle for all panel groups. The association between ANB
      angle and perceived facial attractiveness was highest among orthodontists (R2 =
      0.276, P = 0.001 for males; R2 = 0.285, P = 0.001 for females). However, no
      statistically significant association was found between facial attractiveness and
      LAFH%. Conclusion: Facial sagittal dimensions appeared to influence facial
      aesthetics more than vertical dimensions in middle-aged adults. In their
      perception of facial aesthetics, orthodontists were more influenced by antero
      posterior jaw relationships than dentists and laypersons. The overall perception
      of facial attractiveness related to facial dimensions appeared to differ between
      the panel groups in female and male faces.

PMID- 30215709
TI  - Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot)
      Uveitis.
AB  - Birdshot Uveitis (Birdshot) is a rare eye condition that affects HLA-A29-positive
      individuals and could be considered a prototypic member of the recently proposed
      'MHC-I (major histocompatibility complex class I)-opathy' family. Genetic studies
      have pinpointed the endoplasmic reticulum aminopeptidase (ERAP1) and (ERAP2)
      genes as shared associations across MHC-I-opathies, which suggests ERAP
      dysfunction may be a root cause for MHC-I-opathies. We mapped the ERAP1 and ERAP2
      haplotypes in 84 Dutch cases and 890 controls. We identified association at
      variant rs10044354, which mediated a marked increase in ERAP2 expression. We also
      identified and cloned an independently associated ERAP1 haplotype (tagged by
      rs2287987) present in more than half of the cases; this ERAP1 haplotype is also
      the primary risk and protective haplotype for other MHC-I-opathies. We show that
      the risk ERAP1 haplotype conferred significantly altered expression of ERAP1
      isoforms in transcriptomic data (n = 360), resulting in lowered protein
      expression and distinct enzymatic activity. Both the association for rs10044354
      (meta-analysis: odds ratio (OR) [95% CI]=2.07[1.58-2.71], P = 1.24 * 10(-7)) and
      rs2287987 (OR[95% CI]: =2.01[1.51-2.67], P = 1.41 * 10(-6)) replicated and showed
      consistent direction of effect in an independent Spanish cohort of 46 cases and
      2103 controls. In both cohorts, the combined rs2287987-rs10044354 haplotype
      associated with Birdshot more strongly than either variant alone [meta-analysis:
      P=3.9 * 10(-9)]. Finally, we observed that ERAP2 protein expression is dependent
      on the ERAP1 background across three European populations (n = 3353). In
      conclusion, a functionally distinct combination of ERAP1 and ERAP2 are a hallmark
      of Birdshot and provide rationale for strategies designed to correct ERAP
      function for treatment of Birdshot and MHC-I-opathies more broadly.

PMID- 30215712
TI  - Investigating the impact of cigarette smoking behaviours on DNA methylation
      patterns in adolescence.
AB  - Smoking usually begins in adolescence, and early onset of smoking has been linked
      to increased risk of later life disease. There is a need to better understand the
      biological impact of cigarette smoking behaviours in adolescence. DNA methylation
      profiles related to smoking behaviours and cessation in adulthood have been
      previously identified, but alterations arising from smoking initiation have not
      been thoroughly investigated.We aimed to investigate DNA methylation in the Avon
      Longitudinal Study of Parents and Children in relation to: 1) different smoking
      measures; 2) time since smoking initiation and frequency of smoke exposure; and
      3) latent classes of smoking behaviour.Using 2,620 CpG sites previously
      associated with cigarette smoking, we investigated DNA methylation change in
      relation to own smoking measures, smoke exposure duration and frequency, and
      using longitudinal latent class analysis between different smoking behaviour
      patterns in 968 adolescents.Eleven CpG sites located in seven gene regions were
      differentially methylated in relation to smoking in adolescence. While only AHRR
      (cg05575921) showed a robust consistent pattern of methylation in relation to
      weekly smoking, several CpGs showed differences in methylation among individuals
      who had tried smoking compared with non-smokers. In relation to smoke exposure
      duration and frequency, cg05575921 showed a strong dose-response relationship,
      while there was evidence for more immediate methylation change at other sites.Our
      findings illustrate the impact of cigarette smoking behaviours on DNA methylation
      at some smoking-responsive CpG sites, even among individuals with a short smoking
      history.

PMID- 30215710
TI  - Concordant Changes in Gene Expression and Nucleotides Underlie Independent
      Adaptation to Hydrogen-Sulfide-Rich Environments.
AB  - The colonization of novel environments often involves changes in gene expression,
      protein coding sequence, or both. Studies of how populations adapt to novel
      conditions, however, often focus on only one of these two processes, potentially
      missing out on the relative importance of different parts of the evolutionary
      process. In this study, our objectives were 1) to better understand the
      qualitative concordance between conclusions drawn from analyses of differential
      expression and changes in genic sequence and 2) to quantitatively test whether
      differentially expressed genes were enriched for sites putatively under positive
      selection within gene regions. To achieve this, we compared populations of fish
      (Poecilia mexicana) that have independently adapted to hydrogen-sulfide-rich
      environments in southern Mexico to adjacent populations residing in nonsulfidic
      waters. Specifically, we used RNA-sequencing data to compare both gene expression
      and DNA sequence differences between populations. Analyzing these two different
      data types led to similar conclusions about which biochemical pathways (sulfide
      detoxification and cellular respiration) were involved in adaptation to sulfidic
      environments. Additionally, we found a greater overlap between genes putatively
      under selection and differentially expressed genes than expected by chance. We
      conclude that considering both differential expression and changes in DNA
      sequence led to a more comprehensive understanding of how these populations
      adapted to extreme environmental conditions. Our results imply that changes in
      both gene expression and DNA sequence-sometimes at the same loci-may be involved
      in adaptation.

PMID- 30215711
TI  - Bi-allelic mutations in MYL1 cause a severe congenital myopathy.
AB  - Congenital myopathies are typically characterised by early onset hypotonia,
      weakness and hallmark features on biopsy. Despite the rapid pace of gene
      discovery, ~50% of patients with a congenital myopathy remain without a genetic
      diagnosis following screening of known disease genes. We performed exome
      sequencing on two consanguineous probands diagnosed with a congenital myopathy
      and muscle biopsy showing selective atrophy/hypotrophy or absence of type II
      myofibres. We identified variants in the gene (MYL1) encoding the skeletal muscle
      fast-twitch specific myosin essential light chain (ELC) in both probands. A
      homozygous essential splice acceptor variant (c.479-2A > G, predicted to result
      in skipping of exon 5 was identified in Proband 1, and a homozygous missense
      substitution (c.488T>G, p.(Met163Arg)) was identified in Proband 2. Protein
      modelling of the p.(Met163Arg) substitution predicted it might impede
      intermolecular interactions that facilitate binding to the IQ domain of myosin
      heavy chain, thus likely impacting on the structure and functioning of the myosin
      motor. MYL1 was markedly reduced in skeletal muscle from both probands,
      suggesting that the missense substitution likely results in an unstable protein.
      Knock down of myl1 in zebrafish resulted in abnormal morphology, disrupted muscle
      structure and impaired touch-evoked escape responses, thus confirming that
      skeletal muscle fast-twitch specific myosin ELC is critical for myofibre
      development and function. Our data implicate MYL1 as a crucial protein for
      adequate skeletal muscle function and that MYL1 deficiency is associated with
      severe congenital myopathy.

PMID- 30215714
TI  - Using Identity Theory to Examine the Function of Normative Identities in Living
      with HIV.

PMID- 30215715
TI  - No energy wasted in the fight against vascular inflammation.

PMID- 30215717
TI  - Latinx Use of Traditional Health Care: The Social Network Effect.
AB  - Studies on access to health care among Latinx communities have overlooked (a) the
      use of traditional healers and (b) the role of social networks in seeking
      traditional healers. Framed within the network-episode model, this study aimed to
      examine the role of individual, institutional, and personal network systems in
      the use of curanderxs among Latinxs in the United States. Using a nationally
      representative sample of Latinx adults (N = 3,997) from the 2007 Hispanic
      Healthcare Survey, authors conducted multivariate logistic regression analyses to
      investigate the impact of individual, institutional, and personal network systems
      on the use of curanderxs. Respondents who believed in spiritual healing (adjusted
      odds ratio [AOR] = 3.06) and came from a household that used curanderxs (AOR =
      13.4) were more likely to seek the help of curanderxs when in need of health
      care. The personal network system had most explanatory power in the use of
      curanderxs. The findings add insight to the integration of traditional medicine
      in the provision of health care services to Latinxs in the United States.
      (Authors use the terms "Latinx" and "curanderx" to be inclusive of all gender
      identities.).

PMID- 30215716
TI  - Austerity, measles and mandatory vaccination: cross-regional analysis of
      vaccination in Italy 2000-14.
AB  - Background: Italy has experienced a resurgence in measles since 2015. Although
      much emphasis has been placed on the role of individuals opting out of
      vaccination, here we test the hypothesis that large budget reductions in public
      health spending were also a contributing factor. Methods: Multi-variate
      statistical models were used to assess the relationship between measles, mumps
      and rubella (MMR) coverage and real public health expenditure per-capita across
      Italy's 20 regions covering the period 2000-14. Results: Between 2010 and 2014
      Italy's public health expenditure fell by over 2%, although varying among
      regions. Fixed effects models estimate that each 1% reduction in per-capita
      public health expenditure was associated with a decrease of 0.5 percentage points
      (95% CI: 0.36-0.65 percentage points) in MMR coverage, after adjusting for time
      and regional-specific time trends. The consequences can be illustrated by
      comparing two regions, Lazio, where public health spending fell by 5% and MMR
      coverage by over 3 percentage points, and Sardinia, a historically deprived
      region, where public health spending partly rose and MMR rates remained
      approximately steady. Conclusion: Adoption of austerity policies in the Italian
      health system was found to be significantly associated with declining vaccination
      rates for MMR. However, the recent introduction of mandatory vaccination for
      Italian children may help counteract this trend.

PMID- 30215718
TI  - Bacteroides thetaiotaomicron Ameliorates Colon Inflammation in Preclinical Models
      of Crohn's Disease.
AB  - Background: Alterations in the gut microbiota are strongly associated with the
      development of inflammatory bowel disease (IBD), particularly with Crohn's
      disease, which is characterized by reduced abundance of commensal anaerobic
      bacteria including members of the Bacteroides genus. Our aim was to investigate
      the protective effects of Bacteroides thetaiotaomicron, an abundant member of
      this genus, in different rodent models of IBD. Methods: We assessed the effect of
      B. thetaiotaomicron administration on primary readouts of colitis (weight loss,
      histopathology, and immune parameters) in dextran sodium sulphate (DSS) and
      interleukin-10 knockout (IL10KO) models of IBD. Efficacy of a freeze-dried
      bacterial formulation and a purified recombinant protein of B. thetaiotaomicron
      was also investigated. Results: B. thetaiotaomicron showed protective effects in
      both DSS and IL10KO rodent models, as demonstrated by significant amelioration of
      weight loss, colon shortening, histopathological damage and immune activation.
      This efficacy was not exclusive to actively growing bacterial preparations but
      was retained by freeze-dried cells of B. thetaiotaomicron. A pirin-like protein
      (PLP) of B. thetaiotaomicron, identified by microarray analysis during coculture
      of the bacterial strain with Caco-2 cells, reduced pro-inflammatory NF-kappaB
      signalling in these intestinal epithelial cells. Recombinant PLP partially
      recapitulated the effect of the whole strain in a rat DSS model. Conclusions: B.
      thetaiotaomicron displays strong efficacy in preclinical models of IBD and
      protects against weight loss, histopathological changes in the colon and
      inflammatory markers. These data indicate that the live strain or its products
      may be a novel alternative to current treatment options for Crohn's disease.

PMID- 30215713
TI  - Modifier genes for sudden cardiac death.
AB  - Genetic conditions, even those associated with identical gene mutations, can
      present with variable clinical manifestations. One widely accepted explanation
      for this phenomenon is the existence of genetic factors capable of modifying the
      consequences of disease-causing mutations (modifier genes). Here, we address the
      concepts and principles by which genetic factors may be involved in modifying
      risk for cardiac arrhythmia, then discuss the current knowledge and
      interpretation of their contribution to clinical heterogeneity. We illustrate
      these concepts in the context of two important clinical conditions associated
      with risk for sudden cardiac death including a monogenic disorder (congenital
      long QT syndrome) in which the impact of modifier genes has been established, and
      a complex trait (life-threatening arrhythmias in acute myocardial infarction) for
      which the search for genetic modifiers of arrhythmic risk is more challenging.
      Advances in understanding the contribution of modifier genes to a higher or lower
      propensity towards sudden death should improve patient-specific risk
      stratification and be a major step towards precision medicine.

PMID- 30215719
TI  - Examination of an Integrative Health Care Model for Social Work Practice.
AB  - Social work professionals would benefit by including integrative medicine
      programs and practices in their framework of practice and service delivery to
      clients. In our rapidly changing health care environment, using a model that
      provides a more comprehensive and empowering approach to addressing the medical
      and psychological needs of our clients is warranted. Discussion of holistic
      social work practice and implications for social work education and training will
      be examined through a review of the research and clinical application of a mind
      body program titled the Relaxation Response Resiliency Program (3RP). This client
      centered, strengths-based program can be used in conjunction with traditional
      therapies to empower clients to take part in their own health care by teaching
      noninvasive, self-care, and user-friendly techniques. New research from the
      Benson-Henry Institute for Mind Body Medicine has demonstrated a reduction in
      service utilization and cost savings from participation in 3RP. Research on this
      resiliency health care model will be of interest to social work practitioners,
      educators, and policymakers alike.

PMID- 30215720
TI  - Cohort Profile: The Trondheim Early Secure Study (TESS)-a study of mental health,
      psychosocial development and health behaviour from preschool to adolescence.

PMID- 30215721
TI  - Optimizing vancomycin dosage regimens in relation to high-flux haemodialysis.
AB  - Objectives: To develop a population pharmacokinetic (PK) model for vancomycin in
      adults receiving high-flux haemodialysis (HFHD) in an effort to optimize
      vancomycin dosing in this population. Methods: A population PK model using NONMEM
      was developed using retrospective data collected from 48 vancomycin courses
      administered to patients (n = 37) receiving HFHD. Fixed-dose [1.5 g loading dose
      (LD), 1 g maintenance dose (MD)], literature-adapted weight-based (WBL; 20 mg/kg
      LD, 10 mg/kg MD) and hospital-adapted weight-based (WBH; 25-30 mg/kg LD, 20-25
      mg/kg MD) dosage regimens were then simulated using the Monte Carlo method. The
      PTA was an AUC24/MIC >=400 with success being a PTA >=90%. Results: The data were
      best described using a two-compartment model. It was observed that fixed-dose and
      WBL dosage regimens resulted in a PTA <=90% for most days. The WBH dosing
      achieved a PTA >=90% on most days, but there were supratherapeutic concentrations
      with repeated dosing of vancomycin. If HFHD was delayed by 48-72 h after the LD,
      the PTA would fall below 90%. A dose-optimized regimen was developed: 30 mg/kg LD
      and 10 mg/kg MD given on HFHD days. An additional dose of 500 mg or 1 g was
      administered 24 h after the LD if HFHD occurred 48-72 h post-LD. This dose
      optimized regimen afforded a PTA >=90% on all days of therapy and achieved
      clinically acceptable pre-haemodialysis concentrations. Conclusions: Current
      vancomycin dosage regimens used clinically do not achieve a PTA >=90% for most
      days of therapy for people receiving HFHD. A dose-optimized regimen was
      developed, which could be implemented in clinical practice.

PMID- 30215722
TI  - RSV Strains and Disease Severity.

PMID- 30215724
TI  - Predictors of Reproductive Autonomy among a Rural University Population.
AB  - Reproductive autonomy is necessary for one's overall well-being and is defined as
      the ability to decide and control issues of contraceptive use, pregnancy, and
      birth. Barriers to consistent contraceptive use persist, limiting an individual's
      ability to exercise reproductive autonomy. The present study investigated the
      prevalence of reproductive autonomy and gender beliefs among 468 university
      students (311 women and 157 men) in a rural setting. Participants completed
      surveys measuring reproductive autonomy, attitudes around gender beliefs, and
      demographic questions. Correlations revealed a positive association between
      decision making, communication, and freedom from coercion. Multiple regressions
      found significant predictors to achieving reproductive autonomy, including
      holding healthy gender beliefs, being a woman, using birth control, engaging in
      less religious activity, and being a non-Christian. Social work efforts should
      support young adults to effectively communicate about the use of contraception
      within relationships and to promote healthy gender beliefs. Assessment tools
      should include screening for coercive behaviors such as intimidation, isolation,
      and threats within intimate partnerships. Social work advocacy efforts should
      focus on decreasing the continuing barriers to both comprehensive reproductive
      health care and access to highly effective contraceptives. The specific
      reproductive health needs of rural young adult populations should also be further
      examined.

PMID- 30215725
TI  - Routine antibiotic therapy in dogs increases the detection of antimicrobial
      resistant faecal Escherichia coli.
AB  - Background: Antimicrobial resistance (AMR) is a critical health problem, with
      systemic antimicrobial therapy driving development of AMR across the host
      spectrum. Objectives: This study compares longitudinal carriage, at multiple
      timepoints, of AMR faecal Escherichia coli in dogs undergoing routine
      antimicrobial treatment. Methods: Faecal samples (n = 457) from dogs (n = 127)
      were examined pretreatment, immediately after treatment and 1 month and 3 months
      post-treatment with one of five antimicrobials. Isolates were tested for
      susceptibility to a range of antimicrobials using disc diffusion for each
      treatment group at different timepoints; the presence/absence of corresponding
      resistance genes was investigated using PCR assays. The impact of treatment
      group/timepoint and other risk factors on the presence of resistance [MDR,
      fluoroquinolone resistance, third-generation cephalosporin resistance (3GCR) and
      ESBL and AmpC production] was investigated using multilevel modelling. Samples
      with at least one AMR E. coli from selective/non-selective agar were classed as
      positive. Resistance was also assessed at the isolate level, determining the
      abundance of AMR from non-selective culture. Results: Treatment with beta-lactams
      or fluoroquinolones was significantly associated with the detection of 3GCR, AmpC
      producing, MDR and/or fluoroquinolone-resistant E. coli, but not ESBL-producing
      E. coli, immediately after treatment. However, 1 month post-treatment, only
      amoxicillin/clavulanate was significantly associated with the detection of 3GCR;
      there was no significant difference at 3 months post-treatment for any
      antimicrobial compared with pretreatment samples. Conclusions: Our findings
      demonstrated that beta-lactam and fluoroquinolone antibiotic usage is associated
      with increased detection of important phenotypic and genotypic AMR faecal E. coli
      following routine therapy in vet-visiting dogs. This has important implications
      for veterinary and public health in terms of antimicrobial prescribing and
      biosecurity protocols, and dog waste disposal.

PMID- 30215723
TI  - Long-Term Antipsychotic Effectiveness in First Episode of Psychosis: A 3-Year
      Follow-Up Randomized Clinical Trial Comparing Aripiprazole, Quetiapine, and
      Ziprasidone.
AB  - Background: Different effectiveness profiles among second-generation
      antipsychotics may be a key point to optimize treatment in patients suffering a
      first episode of psychosis to affect long-term outcome. The aim of this study was
      to compare the clinical effectiveness of aripiprazole, ziprasidone, and
      quetiapine in the treatment of first episode of psychosis at 3-year follow-up.
      Method: From October 2005 to January 2011, a prospective, randomized, open-label
      study was undertaken. Two hundred-two first-episode, drug-naive patients were
      randomly assigned to aripiprazole (n=78), ziprasidone (n =62), or quetiapine
      (n=62) and followed-up for 3 years. The primary effectiveness measure was all
      cause of treatment discontinuation. In addition, an analysis based on the
      intention-to-treat principle was conducted in the analysis for clinical efficacy.
      Results: The overall dropout rate at 3 years reached 19.3%. Treatment
      discontinuation rates were significantly different among treatment groups
      (aripiprazole=73.08%, ziprasidone=79.03%, and quetiapine=95.16%) (chi2=11.680;
      P=.001). Statistically significant differences in terms of nonefficacy,
      nonadherence, and side effects were observed among treatment groups along the 3
      year follow-up determining significant differences in time to all-cause
      discontinuation (log-rank=32.260; P=.001). Significant differences between
      treatments were found in the categories of sleepiness/sedation (chi2=9.617;
      P=.008) and increased sleep duration (chi2=6.192; P=.004). No significant
      differences were found in the profile of extrapyramidal symptoms. Patients on
      aripiprazole were more likely to be prescribed benzodiazepines. Conclusions:
      First-episode psychosis patients on quetiapine were more likely to discontinue
      treatment due to nonefficacy. Identifying different discontinuation patterns may
      contribute to optimize treatment selection after first episode of psychosis.

PMID- 30215726
TI  - Evidence of a Causal Effect of Estradiol on Fracture Risk in Men.
AB  - Context: Observational studies indicate that serum estradiol (E2) is more
      strongly associated with bone mineral density (BMD) than serum testosterone (T)
      while both E2 and T associate with fracture risk in men. Objective: To evaluate
      the possible causal effect of serum E2 and T on fracture risk in men. Design,
      Setting, and Participants: A Mendelian Randomization (MR) approach was undertaken
      using individual-level data of genotypes, BMD as estimated by quantitative
      ultrasound of the heel (eBMD), fractures (n=17,650), and relevant covariates of
      175,583 unrelated men of European origin from the UK Biobank. The genetic
      instruments for serum E2 and T were taken from the most recent large scale GWAS
      meta-analyses on these hormones in men. Results: MR analyses demonstrated a
      causal effect of serum E2 on eBMD and fracture risk. A 1 SD (or 9.6 pg/ml)
      genetically instrumented decrease in serum E2 was associated with a 0.38 SD
      decrease in eBMD (p-value 9.7 x 10-74) and an increased risk of any fracture (OR
      1.35, 95% CI, 1.18-1.55), non-vertebral major osteoporotic fractures (OR 1.75,
      95% CI, 1.35-2.27) and wrist fractures (OR 2.27, 95% CI, 1.62-3.16). These causal
      effects of serum E2 on fracture risk were robust in sensitivity analyses and
      remained unchanged in stratified analyses for age, BMI, eBMD, smoking status, and
      physical activity. MR analyses revealed no evidence of a causal effect of T
      levels on fracture risk. Conclusion: Our findings provide the first evidence of a
      robust causal effect of serum E2, but not T, on fracture risk in men.

PMID- 30215727
TI  - Evaluating temporal patterns of snakebite in Sri Lanka: the potential for higher
      snakebite burdens with climate change.
AB  - Background: Snakebite is a neglected tropical disease that has been overlooked by
      healthcare decision makers in many countries. Previous studies have reported
      seasonal variation in hospital admission rates due to snakebites in endemic
      countries including Sri Lanka, but seasonal patterns have not been investigated
      in detail. Methods: A national community-based survey was conducted during the
      period of August 2012 to June 2013. The survey used a multistage cluster design,
      sampled 165 665 individuals living in 44 136 households and recorded all recalled
      snakebite events that had occurred during the preceding year. Log-linear models
      were fitted to describe the expected number of snakebites occurring in each
      month, taking into account seasonal trends and weather conditions, and addressing
      the effects of variation in survey effort during the study and of recall bias
      amongst survey respondents. Results: Snakebite events showed a clear seasonal
      variation. Typically, snakebite incidence is highest during November-December
      followed by March-May and August, but this can vary between years due to
      variations in relative humidity, which is also a risk factor. Low relative
      humidity levels are associated with high snakebite incidence. If current climate
      change projections are correct, this could lead to an increase in the annual
      snakebite burden of 31.3% (95% confidence interval: 10.7-55.7) during the next 25
      50 years. Conclusions: Snakebite in Sri Lanka shows seasonal variation.
      Additionally, more snakebites can be expected during periods of lower-than
      expected humidity. Global climate change is likely to increase the incidence of
      snakebite in Sri Lanka.

PMID- 30215728
TI  - SIN3B promotes integrin alphaV subunit gene transcription and cell migration of
      hepatocellular carcinoma.
AB  - Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many
      genes. Here we show a different regulation mechanism of integrin alphaV gene
      expression by SIN3B in human hepatocellular carcinoma (HCC). We first observed a
      close relationship between Integrin alphaV and SIN3B expressions in HCC patients
      and tumor cell lines with different metastatic potentials. Overexpression of
      SIN3B significantly accelerated the cell migration rate of SMMC-7721, but failed
      when integrin alphaV expression was silenced. Interestingly, SIN3B stimulated
      integrin alphaV subunit promoter activity only in the presence of sulfatide.
      Importantly, SIN3B was identified in the complex with sulfatide by mass
      spectrometry. Fat blot assay indicated that SIN3B specifically interacted with
      sulfatide. Molecular modeling suggested that sulfatide induced the conformational
      change of SIN3B from compacted alpha-helices to a relaxed beta-sheet in PAH2
      domain. The data of immunoprecipitation and ChIP assay indicated that altered
      SIN3B lost the binding affinity with MAD1 and HDAC2, which reduced the
      recruitment of HDAC2 on integrin alphaV gene promoter and prevented the
      deacetylation of the histone 3. In conclusion, this study demonstrated that SIN3B
      promoted the transcriptional activation of the integrin alphaV subunit gene
      promoter by reducing interaction with HDAC2.

PMID- 30215730
TI  - Does Only Sex Matter? Complexity of the Association Between Vdr Gene BsmI Single
      Nucleotide Polymorphism and Immune Response in IBD.

PMID- 30215729
TI  - Propionate and butyrate induce gene expression of monocarboxylate transporter 4
      and cluster of differentiation 147 in cultured rumen epithelial cells derived
      from preweaning dairy calves.
AB  - Short-chain fatty acids (SCFAs) are the main source of energy for postweaning
      ruminants. The monocarboxylic acid transporters, MCT1 and MCT4, are thought to
      contribute to the absorption of SCFAs from the surface of the rumen following
      weaning. The present study measured changes in MCT1 and MCT4 expression in
      ruminal epithelial cells isolated from male preweaning (22 to 34 d old, n = 6)
      and postweaning (55 to 58 d old, n = 8) calves after euthanasia and sought to
      examine whether SCFAs stimulate the expression of these transporters. In the
      current study, cluster of differentiation 147 (CD147) gene expression in the
      rumen was also investigated since CD147 has been considered to act as ancillary
      protein for MCT1 and MCT4 to express their correct function. The gene expression
      levels of MCT1, MCT4, and CD147 in the rumen were found to be significantly
      higher in postweaning calves than in preweaning calves. Strong MCT1
      immunoreactivity was detected in both the stratum basale (SB) and the stratum
      spinosum (SS) in postweaning ruminal epithelium. Expression of MCT1 in preweaning
      calves was localized to a specific region of the SB and of the SS. MCT4
      immunopositive cells were detected in the stratum corneum (SC) of the ruminal
      epithelium in postweaning calves. However, only a low level of signal was
      detected in the SC of preweaning animals. Furthermore, in vitro experiments,
      ruminal epithelial cells were incubated for 24 h with acetate (0.04, 0.4, and 4
      mM), propionate (0.2, 2, and 20 mM), butyrate (0.1, 1, and 10 mM), or beta
      hydroxybutyrate (BHBA; 0.1, 1, and 10 mM), respectively. Both propionate and
      butyrate induced an increase in the gene expression levels of MCT4 and CD147, but
      did not affect MCT1 gene expression. There are no significant effects of acetate
      and BHBA treatment on these gene expressions. Taken together, these results
      suggest that an increase in MCT4 and CD147 gene expression in the ruminal
      epithelium of postweaning calves is likely to be due to the effects of propionate
      and butyrate derived from a solid-based diet, which may contribute to ruminal
      development following weaning.

PMID- 30215731
TI  - Can Placental Corticotropin-Releasing Hormone Inform Timing of Antenatal
      Corticosteroid Administration?
AB  - Context: Antenatal corticosteroids commonly are administered to pregnant women at
      risk of delivering between 23 and 34 gestational weeks, providing crucial
      benefits to fetal lung maturation and reducing risk of neonatal morbidity and
      mortality. Corticosteroids are maximally efficacious for lung maturation when
      administered within 2 to 7 days of delivery. Accurately identifying the timing of
      preterm delivery is thus critical to ensure that antenatal corticosteroids are
      administered within a week of delivery and to avoid unnecessary administration to
      women who will deliver at term. A plausible biomarker for predicting time of
      delivery is placental corticotropin-releasing hormone (pCRH). Objective: The
      current study assesses whether pCRH concentrations predict time to delivery, and
      specifically which women will deliver within a week of treatment. Design: pCRH
      concentrations were evaluated prior to administration of the corticosteroid
      betamethasone and timing of delivery was recorded. Participants: 121 women with
      singleton pregnancies who were prescribed betamethasone. Results: Elevated pCRH
      concentrations were associated with a shorter time from treatment to delivery.
      ROC curves revealed that pCRH may improve the precision of predicting preterm
      delivery. Conclusions: In the current sample, pCRH concentrations predicted the
      likelihood of delivering within one week of corticosteroid treatment. Current
      findings suggest that pCRH may be a diagnostic indicator of impending preterm
      delivery. Increasing the precision in predicting time to delivery could inform
      when to administer antenatal corticosteroids, thus maximizing benefits and
      reducing the likelihood of exposing fetuses who will be delivered at term.

PMID- 30215732
TI  - The Role of Social Workers in Immigrant and Refugee Welfare.

PMID- 30215733
TI  - Novel synthetic polymyxins kill Gram-positive bacteria.
AB  - Background: Staphylococcus aureus, including 'superbug' MRSA, is a major cause of
      nosocomial infections. In the European Union, up to 171 200 new nosocomial MRSA
      infections are acquired annually, and in the USA S. aureus causes more deaths
      than HIV/AIDS and tuberculosis combined. MRSA is also the first group of
      pathogens that infect the pulmonary tract in young patients with cystic fibrosis.
      Objectives: We describe two newly developed and synthesized colistin (polymyxin
      E)-inspired molecules. Methods: A collection of several isolates of S. aureus
      [including MRSA and vancomycin-resistant S. aureus (VRSA)] was tested. To check
      the antimicrobial activity, we performed time-kill curves, growth curves, biofilm
      eradication, toxicity and isothermal titration calorimetry. Results: Both
      peptides showed high antimicrobial activities (MIC 4 mg/L) and low relative
      toxicities (selectivity index close to 23). Conclusions: Successful production of
      polymyxin-scaffold molecules active against S. aureus, both MRSA and VRSA, opens
      up new approaches to the treatment of these complicated infections.

PMID- 30215734
TI  - Ethnicity May Be Important for Studying the Role of the Microbiome and Vitamin D
      Receptor in IBD.

PMID- 30215736
TI  - Giant pulmonary arteriovenous malformation revealed by recurrent pregnancy loss.

PMID- 30215735
TI  - Lixisenatide reduces chylomicron triacylglycerol due to increased clearance.
AB  - Context: GLP-1 agonists control postprandial glucose and lipid excursion in type
      2 diabetes; however the mechanism(s) are unclear. Objective: To determine the
      mechanism(s) of postprandial lipid and glucose control with lixisenatide (GLP-1
      analogue) in type 2 diabetes. Design: Randomised, double-blind, cross-over study.
      Setting: Centre for Diabetes, Endocrinology, and Research, Royal Surrey County
      Hospital, Guildford, UK. Patients: Eight obese men with type 2 diabetes (57.3+/
      1.9yrs; BMI 30.3+/-1.0kg/m2, HbA1C 66.5+/-2.6mmol/mol, [8.2+/-0.3%]).
      Interventions: Two metabolic studies, four-weeks after lixisenatide or placebo;
      with cross-over and repetition of studies. Main outcome measures: Study one: very
      low density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG)
      kinetics were measured with iv bolus of [2H5]glycerol in a 12h study, with hourly
      feeding. Oral [13C]triolein, in a single meal, labelled enterally-derived TAG.
      Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal
      (plus acetaminophen to measure gastric emptying) and variable iv [6,6-2H2]glucose
      infusion. Results: Study one: CM-TAG (but not VLDL-TAG) pool-size, was lower with
      lixisenatide (P=0.046). Lixisenatide reduced CM [13C]oleate AUC60-480min
      concentration (P=0.048) and increased CM-TAG clearance; with no effect on CM-TAG
      production rate. Study two: postprandial glucose and insulin AUC0-240min were
      reduced with lixisenatide (P=0.0051, P<0.05). Total glucose production rate (Ra)
      (P=0.015), Rameal (P=0.0098) and acetaminophen AUC0-360min (P=0.006) were lower
      with lixisenatide than placebo. Conclusions: Lixisenatide reduced [13C]oleate
      concentration, derived from a single meal in CM-TAG, as well as glucose Rameal,
      through delayed gastric emptying. However day-long CM production, measured with
      repeated meal-feeding, was not reduced by lixisenatide and decreased CM-TAG
      concentration was due to increased CM-TAG clearance.

PMID- 30215737
TI  - Distinct Biological Phenotypes of Marburg and Ravn Virus Infection in Macaques.
AB  - Filoviruses are among the most pathogenic infectious agents known to human, with
      high destructive potential, as evidenced by the recent Ebola virus epidemic in
      West Africa. As members of the filovirus family, marburgviruses have caused
      similar devastating outbreaks, albeit with lower case numbers. In this study we
      compare the pathogenesis of Ravn virus (RAVV) and Marburg virus (MARV) strains
      Angola, Musoke, and Ozolin in rhesus and cynomolgus macaques, the 2 nonhuman
      primate species most commonly used in filovirus research. Our results reveal the
      most pathogenic MARV strain to be Angola, followed by Musoke, whereas Ozolin is
      the least pathogenic. We also demonstrate that RAVV is highly pathogenic in
      cynomolgus macaques but less pathogenic in rhesus macaques. Our results
      demonstrate a preferential infection of endothelial cells by MARVs; in addition,
      analysis of tissue samples suggests that lymphocyte and hepatocyte apoptosis
      might play a role in MARV pathogenicity. This information expands our knowledge
      about pathogenicity and virulence of marburgviruses.

PMID- 30215738
TI  - A Multisectoral Emergency Response Approach to a Cholera Outbreak in Zambia:
      October 2017-February 2018.

PMID- 30215739
TI  - Household Water Treatment and Cholera Control.
AB  - Water, sanitation, and hygiene are one part of a cholera control strategy.
      Household water treatment (HWT) in particular has been shown to improve the
      microbiological quality of stored water and reduce the disease burden. We
      conducted a systematic review of published and gray literature to determine the
      outcomes and impacts of HWT in preventing cholera specifically. Fourteen
      manuscripts with 18 evaluations of HWT interventions in cholera were identified.
      Overall, a moderate quality of evidence suggests that HWT interventions reduce
      the burden of disease in cholera outbreaks and the risk of disease transmission.
      Appropriate training for users and community health worker follow-up are
      necessary for use. Barriers to uptake include taste and odor concerns, and
      facilitators include prior exposure, ease of use, and links to preexisting
      development programming. Further research on local barriers and facilitators, HWT
      filters, scaling up existing development programs, program sustainability,
      integrating HWT and oral cholera vaccine, and monitoring in low-access
      emergencies is recommended.

PMID- 30215740
TI  - Polycystin-1 regulates bone development through an interaction with the
      transcriptional co-activator taz.
AB  - Polycystin-1 (PC1), encoded by the PKD1 gene that is mutated in Autosomal
      Dominant Polycystic Kidney disease, regulates a number of processes including
      bone development. Activity of the transcription factor RunX2, which controls
      osteoblast differentiation, is reduced in Pkd1 mutant mice but the mechanism
      governing PC1 activation of RunX2 is unclear. PC1 undergoes regulated cleavage
      that releases its C-terminal tail, which translocates to the nucleus to modulate
      transcriptional pathways involved in proliferation and apoptosis. We find that
      the cleaved carboxy-terminal tail of PC1 (PC1-CTT) stimulates the transcriptional
      co-activator TAZ (Wwtr1), an essential co-activator of RunX2. PC1-CTT physically
      interacts with TAZ, stimulating RunX2 transcriptional activity in pre-osteoblast
      cells in a TAZ-dependent manner. The PC1-CTT increases the interaction between
      TAZ and RunX2 and enhances the recruitment of the p300 transcriptional co
      regulatory protein to the TAZ/RunX2/PC1-CTT complex. Zebrafish injected with
      morpholinos directed against pkd1 manifest severe bone calcification defects and
      a curly tail phenotype. Injection of mRNA encoding the PC1-CTT into pkd1-morphant
      fish restores bone mineralization and reduces the severity of the curly tail
      phenotype. These effects are abolished by co-injection of morpholinos directed
      against TAZ. Injection of mRNA encoding a dominant-active TAZ construct is
      sufficient to rescue both the curly tail phenotype and the skeletal defects
      observed in pkd1-morpholino treated fish. Thus, TAZ constitutes a key mechanistic
      link through which PC1 mediates its physiological functions.

PMID- 30215741
TI  - Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm
      growth, adherence and phagocytosis in vitro and pathogenicity in vivo.
AB  - Streptococcus pneumoniae, the most common cause of bacterial pneumonia, has
      developed a wide range of virulence factors to evade the immune system of which
      the polysaccharide capsule is the most important one. Formation of this capsule
      is dependent on the cps gene locus, but also involves other genes-like galU. The
      pyrophosphorylase encoded by galU plays a role in the UDP-glucose metabolism of
      prokaryotes and is required for the biosynthesis of capsular polysaccharides. In
      this paper, the effect of a galU mutation leading to a dysfunctional UDP-glucose
      pyrophosphorylase (UDPG:PP) on in vitro biofilm biomass, adherence to lung
      epithelial cells and macrophage phagocytosis is studied. Last, in vivo virulence
      using a Galleria mellonella model has been studied. We show that the mutation
      improves streptococcal adherence to epithelial cells and macrophage phagocytosis
      in vitro, while there is no definitive correlation on biofilm formation between
      parent and mutant strains. Moreover, in vivo virulence is attenuated for all
      mutated strains. Together, these results demonstrate that a galU mutation in S.
      pneumoniae influences host cell interactions in vitro and in vivo and can
      strongly influence the outcome of a streptococcal infection. As such, UDPG:PP is
      worth investigating further as a potential drug target.

PMID- 30215742
TI  - DICER1 regulates antibacterial function of epididymis by modulating transcription
      of beta-defensins.
AB  - DICER1 is a key enzyme responsible for the maturation of microRNAs. Recent
      evidences suggested that DICER1 and microRNAs expressed in epididymis were
      involved in the control of male fertility. However, the exact mechanism remains
      to be elucidated. Here, we created a mouse line by targeted disruption of Dicer1
      gene in the principal cells of distal caput epididymis. Our data indicated that a
      set of beta-defensin genes were downregulated by DICER1 rather than by microRNAs.
      Moreover, DICER1 was significantly enriched in the promoter of beta-defensin gene
      and controlled transcription. Besides, the antibacterial ability of the adult
      epididymis significantly declined upon Dicer1 deletion both in vitro and in vivo.
      And a higher incidence of reproductive defect was observed in middle aged Dicer1
      /- males. These results suggest that DICER1 plays an important role in
      transcription of beta-defensin genes, which are associated with the natural
      antibacterial properties in a microRNA-independent manner, and further impacts
      the male fertility.

PMID- 30215743
TI  - The independent role of deprivation in abdominal obesity beyond income poverty. A
      population-based household survey in Chinese adults.
AB  - Background: Individual-level deprivation takes into account the non-monetary
      aspects of poverty that neither income poverty nor socio-economic factors could
      fully capture; however, it has rarely been considered in existing studies on
      social inequality in obesity. Therefore, we examined the associations of
      deprivation, beyond income poverty, with both general and abdominal obesity.
      Methods: A territory-wide two-stage stratified random sample of 2282 community
      dwelling Hong Kong adults was surveyed via face-to-face household interviews
      between 2014 and 2015. Deprivation was assessed by a Deprivation Index specific
      to the Hong Kong population. General obesity was defined as body mass index (BMI)
      >= 25 kg/m2, while abdominal obesity was defined as waist circumference (WC) >=
      90 cm/80 cm for male/female. Multivariable binary logistic regressions were
      performed. Results: Deprivation was independently associated with abdominal
      obesity (odds ratios (OR) = 1.68; 95% confidence intervals (CI): 1.27-2.22);
      however, no significant association was found with general obesity (OR=1.03; CI:
      0.77-1.38). After additional adjustment for BMI, deprivation remained strongly
      associated with abdominal obesity (OR=2.00; CI: 1.41-2.83); and after further
      adjustment for WC, deprivation had a marginal inverse association with general
      obesity (OR=0.72; CI: 0.51-1.01). Conclusions: Deprivation is an important risk
      factor of abdominal obesity and plays a critical role in capturing the
      preferential abdominal fat deposition beyond income poverty.

PMID- 30215746
TI  - Undersampling Genomes has Biased Time and Rate Estimates Throughout the Tree of
      Life.

PMID- 30215745
TI  - Acute Sarcomeric M-Line Disease Associated With ATP Synthase Subunit alpha
      Autoantibodies in Ankylosing Spondylitis.
AB  - M-line is the narrow transverse band located in the center of the sarcomeric A
      band that is mainly responsible for the stabilization of myosin thick filaments.
      A 27-year-old male patient with a positive medical history for ankylosing
      spondylitis presented with one month of proximal upper limb muscle weakness
      associated with pain on both acromioclavicular joints. A biopsy of deltoid muscle
      documented the disappearance of M-line, the misalignment of myofilaments, and the
      loss of the distinction between the A and I bands. Complete resolution of muscle
      weakness occurred after one year of treatment with antiTNFalpha agent Etanercept.
      Because of the acute onset of symptoms and the recovery after immunosuppressive
      treatment we hypothesized that an immune-mediated mechanism was responsible for
      the muscle disorder. The serum IgG-mediated autoreactivity to skeletal muscle
      antigens resolved by bidimensional electrophoresis was assessed in the described
      patient and compared with that of control subjects. The comparative analysis of
      the immunoreactive spots revealed that ATP synthase subunit alpha is specifically
      recognized by patient's serum, suggesting that the protein might represent a
      putative antigenic target in the disease. This study reports an acute reversible
      myopathy pathologically characterized by M-line involvement and associated with
      serological antibodies to the subunit alpha of ATP synthase.

PMID- 30215744
TI  - Effects of constant or intermittent high temperature on egg production, feed
      intake, and hypothalamic expression of antioxidant and pro-oxidant enzymes genes
      in laying ducks.
AB  - Heat stress is a major environmental factor contributing to lower production of
      poultry. The objective of present study was to evaluate the influence of constant
      or intermittent high temperature on the production performance and redox status
      of plasma and hypothalamus in laying ducks. A total of 288 weight- and laying
      matched laying ducks were randomly assigned to 1 of 4 treatments (each with 6
      replicates of 12 birds): control, pair-fed, constant high temperature (24 h, 34
      +/- 1 degrees C), and intermittent high temperature (10 h, 34 +/- 1 degrees C).
      Blood and hypothalamic tissue samples were collected on days 1, 21, and 55 to
      determine redox status. Average daily feed intake and egg weight was reduced (P <
      0.001) during imposition of both high-temperature treatments but was not
      different (P > 0.05) among the treatments during the recovery period. Lower (P <
      0.05) egg mass was observed in pair-fed and intermittent high-temperature
      treatment during high-temperature period and in constant high temperature during
      the recovery period. Haugh units from high temperature-treated ducks were
      significantly lower than those from control or pair-fed ducks (P < 0.05) during
      the high-temperature period. Both models of heat exposure decreased plasma
      concentrations of glutathione (GSH) at day 1, and constant high temperature
      decreased plasma activity of GSH peroxidase (GSH-PX) at day 21 (P < 0.05).
      Hypothalamic expression of antioxidant genes GSH reductase (GR) and mitochondrial
      NADH dehydrogenase subunit (Complex Iota) were decreased by both high-temperature
      treatments at day 1. Hypothalamic expression of genes for pro-oxidant enzymes
      cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and cytochrome P450 7A1
      (CYP7A1) were decreased (P < 0.05) by both models of high temperature but
      transcripts of cyclooxygenase-1 (COX-1) of ducks that were pair-fed or were
      exposed to constant high temperature were increased at day 21. The transcripts of
      NADPH oxidase 1 (NOX-1) were decreased at day 1 by both high-temperature
      treatments (P < 0.05) but increased during the recovery period. These results
      indicate that, for laying ducks, intermittent high temperature caused much
      greater negative production performance effects than constant high temperature
      during high-temperature period, but laying ducks exposed to constant high
      temperature tend to take longer to recover their production performance. High
      temperature stress, either constant or intermittent, altered hypothalamic
      expression of antioxidation and pro-oxidation genes.

PMID- 30215748
TI  - The Effect of the Alternative Prey, Paramecium caudatum (Peniculida:
      Parameciidae), on the Predation of Culex pipiens (Diptera: Culicidae) by the
      Copepods Macrocyclops albidus and Megacyclops viridis (Cyclopoida: Cyclopidae).
AB  - Biological control can be an effective tool to combat public health risks
      associated with mosquito-borne disease. However, target impacts of biological
      control agents may be reduced by biotic contexts such as the presence of
      alternative prey. In turn, this can impede our ability to realistically assess
      biocontrol agent efficacy. Here, we examine the effects of alternative ciliate
      prey on the predation potential of two cyclopoid copepods, Macrocyclops albidus
      Jurine (Cyclopoida: Cyclopidae) and Megacyclops viridis Jurine (Cyclopoida:
      Cyclopidae), toward larvae of the West Nile virus vector mosquito Culex pipiens
      Linnaeus (Diptera: Culicidae). Using functional responses (FRs; resource use
      under different resource densities), we demonstrate that both copepods exhibit
      potentially destabilizing type II FRs toward mosquito prey. However, where the
      alternative prey was present, we observed species-specific modulations to FR form
      and magnitude. For M. albidus, FRs remained type II where ciliate prey were
      present, however, maximum feeding rates on mosquito larvae were reduced.
      Conversely, for M. viridis, FRs moved toward more stabilizing type III, while
      maximum feeding rates on mosquito larvae were not significantly reduced. While
      both species of cyclopoid copepod were able to effectively target and consume
      larval mosquitoes in the presence of alternative prey, we demonstrate that
      overall efficacies may be reduced in aquatic habitats which contain multiple prey
      types. We thus advocate that biotic contexts such as prey selectivity should be
      integrated into predatory biocontrol agent examinations for mosquitoes which
      vector pathogens and parasites, to more holistically assess their efficacy.

PMID- 30215747
TI  - Relative bioavailability of ultrafine sodium selenite for broilers fed a
      conventional corn-soybean meal diet.
AB  - The particle size of selenium (Se) sources could affect Se absorption and
      utilization, and thus it is hypothesized that the Se bioavailability might be
      higher in ultrafine sodium selenite (USSe) than in sodium selenite (SSe) for
      broilers because of USSe's smaller particle size. An experiment was conducted to
      investigate the relative bioavailability of Se as USSe relative to SSe for
      broiler chicks fed a conventional corn-soybean meal diet. A total of 504 one-d
      old Arbor Acres commercial male broilers were randomly allotted to 1 of 7
      treatments with 6 replicates per treatment in a completely randomized design
      involving in a 2 (Se sources) * 3 (added Se levels) factorial arrangement of
      treatments plus a Se-unsupplemented control diet containing 0.05 mg Se/kg by
      analysis for 21 d. The 2 Se sources were USSe and SSe, and the 3 added Se levels
      were 0.15, 0.30, or 0.45 mg Se/kg. The Se concentrations, glutathione peroxidase
      (GSH-Px) activities, and mRNA relative abundances in plasma, liver, or pancreas
      of broilers on day 14 and 21 were determined. The results showed that Se
      concentrations, GSH-Px activities in plasma, liver, and pancreas, and mRNA
      relative abundances in the liver and pancreas of broilers on day 14 and 21
      increased linearly (P < 0.05) as the added Se-level increased. Furthermore, a
      difference (P < 0.05) between USSe and SSe was detected for GSH-Px mRNA relative
      abundance in the pancreas of broilers on day 14. On the basis of the slope ratios
      from the multiple linear regression of the pancreatic GSH-Px mRNA relative
      abundance of broilers at 14 d of age on daily dietary analyzed Se intake, the Se
      bioavailability of USSe relative to SSe (100%) was 158% (P < 0.05). The results
      from this study indicated that the Se from USSe was more available to broilers
      than the Se from SSe in enhancing the pancreatic GSH-Px mRNA expression.

PMID- 30215749
TI  - Psychometric Properties of Assessments of Cognition in Infants With Cerebral
      Palsy or Motor Impairment: A Systematic Review.
AB  - Objective: Approximately 50% of people with cerebral palsy have a cognitive
      impairment. However, many tools used to assess cognition in infants require
      almost normal fine motor ability, and thus may not accurately reflect cognitive
      abilities of infants with cerebral palsy or other motor impairments. This
      systematic review aimed to evaluate the psychometric properties of cognitive
      assessment tools for infants aged 0-24 months with motor impairments and to make
      recommendations about the most appropriate cognitive assessment tools for the
      purpose of discrimination, prediction, and evaluation. Method: A systematic
      review was conducted. CINAHL, Embase, ERIC, Medline, PsycINFO, and SCOPUS
      databases were searched to identify studies reporting on 1 or more psychometric
      properties of a standardized cognitive assessment tool or questionnaire in a
      sample/subsample of infants with motor impairment. Of the 4,480 articles
      reviewed, 9 assessment tools were identified in 20 publications, which met our
      inclusion criteria. Articles were appraised using the COnsensus-based Standards
      for the selection of health Measurement INstruments to assess study rigor. The
      GRADE framework was applied to develop recommendations for clinical practice.
      Results: The Mayes Motor-Free Compilation, Fagan Test of Infant Intelligence, and
      Bayley-III Low Motor/Vision have predictive and/or discriminative utility in this
      population. The Mullen Scales of Early Learning was the only tool with
      psychometric research available examining responsivity to change. Conclusions:
      Assessment tools with low-motor/motor-free accommodations have greater accuracy
      in estimating cognitive abilities of infants with motor impairment than
      conventional norm-referenced tests. There, however, remains a significant paucity
      of research in this area.

PMID- 30215751
TI  - Renal Replacement Therapy Capability for the Treatment of Combat-Associated Acute
      Kidney Injury: A Historical Perspective to Plan for Future Conflicts.
AB  - Trauma-induced acute kidney injury (AKI) has affected many U.S. warfighters
      throughout history. We seek to provide a historical review of the epidemiology of
      combat-acquired AKI and to highlight the importance of adapting current renal
      replacement therapy (RRT) capabilities to prepare for the next armed conflict.
      While severe AKI was rare in the recent conflicts in Iraq and Afghanistan, an
      analysis of prior wars suggests that it will be more common in future combat
      operations characterized by prolonged evacuation times, limited resuscitation
      capabilities, and delayed aeromedical evacuation. Therefore, the military
      community must develop RRT capabilities to satisfy the demands of prolonged field
      care and austere environments. We propose a series of solutions such as re
      enforcing forward deployment of conventional RRT capabilities as well as novel
      therapies such as improvised dialysis systems or sorbent-based RRT.

PMID- 30215752
TI  - High-Reliability Uncaged: Safety Lessons From Army Aviation.

PMID- 30215750
TI  - Non-canonical translation initiation of the spliced mRNA encoding the human T
      cell leukemia virus type 1 basic leucine zipper protein.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T
      cell leukemia (ATL). The HTLV-1 basic leucine zipper protein (HBZ) is expressed
      in all cases of ATL and is directly associated with virus pathogenicity. The two
      isoforms of the HBZ protein are synthesized from antisense messenger RNAs (mRNAs)
      that are either spliced (sHBZ) or unspliced (usHBZ) versions of the HBZ
      transcript. The sHBZ and usHBZ mRNAs have entirely different 5'untranslated
      regions (5'UTR) and are differentially expressed in cells, with the sHBZ protein
      being more abundant. Here, we show that differential expression of the HBZ
      isoforms is regulated at the translational level. Translation initiation of the
      usHBZ mRNA relies on a cap-dependent mechanism, while the sHBZ mRNA uses internal
      initiation. Based on the structural data for the sHBZ 5'UTR generated by SHAPE in
      combination with 5' and 3' deletion mutants, the minimal region harboring IRES
      activity was mapped to the 5'end of the sHBZ mRNA. In addition, the sHBZ IRES
      recruited the 40S ribosomal subunit upstream of the initiation codon, and IRES
      activity was found to be dependent on the ribosomal protein eS25 and eIF5A.

PMID- 30215754
TI  - An L,L-diaminopimelate aminotransferase mutation leads to metabolic shifts and
      growth inhibition in Arabidopsis.
AB  - Lysine (Lys) connects the mitochondrial electron transport chain to amino acid
      catabolism and the tricarboxylic acid cycle. However, our understanding of how a
      deficiency in Lys biosynthesis impacts plant metabolism and growth remains
      limited. Here, we used a previously characterized Arabidopsis mutant (dapat) with
      reduced activity of the Lys biosynthesis enzyme L,L-diaminopimelate
      aminotransferase to investigate the physiological and metabolic impacts of
      impaired Lys biosynthesis. Despite displaying similar stomatal conductance and
      internal CO2 concentration, we observed reduced photosynthesis and growth in the
      dapat mutant. Surprisingly, whilst we did not find differences in dark
      respiration between genotypes, a lower storage and consumption of starch and
      sugars was observed in dapat plants. We found higher protein turnover but no
      differences in total amino acids during a diurnal cycle in dapat plants.
      Transcriptional and two-dimensional (isoelectric focalization/SDS-PAGE) proteome
      analyses revealed alterations in the abundance of several transcripts and
      proteins associated with photosynthesis and photorespiration coupled with a high
      glycine/serine ratio and increased levels of stress-responsive amino acids. Taken
      together, our findings demonstrate that biochemical alterations rather than
      stomatal limitations are responsible for the decreased photosynthesis and growth
      of the dapat mutant, which we hypothesize mimics stress conditions associated
      with impairments in the Lys biosynthesis pathway.

PMID- 30215755
TI  - Autonomic Symptoms in Gulf War Veterans Evaluated at the War Related Illness and
      Injury Study Center.
AB  - Introduction: We characterized the presence of autonomic symptoms in a sample of
      Veterans with Gulf War Illness (GWI) using the Composite Autonomic Symptom Scale
      (COMPASS-31). In addition, we examined the report of autonomic symptoms across
      comorbid mental health conditions in this sample. Materials and Methods: Case
      series follow-up of Gulf War veterans evaluated by the War Related Illness and
      Injury Study Center (WRIISC) between 2011 and 2016 (n = 153). Phone-based
      interview consisted of questionnaires designed to investigate autonomic symptoms,
      physical symptoms, mental health conditions, and GWI. Sixty-One Veterans agreed
      to participate in this follow-up arm of the study. We restricted our analysis to
      only those Veterans meeting CDC and/or Kansas criteria for GWI, leaving us with a
      sample of 56 Veterans. Results: Veterans in our sample were, male (n = 55, 98%),
      49 (+/-6.8) years old and used 8 (+/-6.6) medications. The mean COMPASS-31 score
      for our sample was 45.6 (+/-18.3). There were no differences in reports of
      autonomic symptoms between participants who screened positive or negative for
      depression or post-traumatic stress disorder, but COMPASS-31 scores were higher
      among those who screened positive for anxiety (49.6 (+/-16.0)) compared with
      those who screened negative (29.3 (+/-18.9)) (p < 0.001). Conclusions: The
      elevated COMPASS-31 scores suggest that there may be autonomic dysfunction
      present in our sample of Veterans with GWI, consistent with other published
      reports. Additionally, we believe that the high scores on the anxiety measure may
      reflect assessment of physiological symptoms that are not specific to anxiety,
      and may reflect GWI symptoms. Objective physiological tests of the autonomic
      nervous system are warranted to better characterize autonomic function and the
      clinical relevance of COMPASS-31 in this population.

PMID- 30215756
TI  - Linear Lichen Planus in the Setting of Annual Vaccination.
AB  - Vaccines have a well-demonstrated therapeutic benefit. However, the spectrum of
      potential dermatologic vaccine side effects ranges from localized skin irritation
      to acute and delayed response. Currently, there are limited published data
      correlating dermatoses with alterations in the immune system following
      vaccination. The mechanism by which group A beta-hemolytic streptococci may
      precede the manifestation of guttate psoriasis is included as a mechanism
      foundation as we further describe the immunopathogenesis of immune-mediated
      linear dermatoses. We present a rare case of linear lichen planus following
      intramuscular influenza vaccination, not associated with an injection site
      reaction. Immune-related dermatoses may be underreported, and a vaccine history
      should be considered in all patients with a skin condition that is otherwise
      attributed as idiopathic.

PMID- 30215753
TI  - Structural and mechanistic basis for preferential deadenylation of U6 snRNA by
      Usb1.
AB  - Post-transcriptional modification of snRNA is central to spliceosome function.
      Usb1 is an exoribonuclease that shortens the oligo-uridine tail of U6 snRNA,
      resulting in a terminal 2',3' cyclic phosphate group in most eukaryotes,
      including humans. Loss of function mutations in human Usb1 cause the rare
      disorder poikiloderma with neutropenia (PN), and result in U6 snRNAs with
      elongated 3' ends that are aberrantly adenylated. Here, we show that human Usb1
      removes 3' adenosines with 20-fold greater efficiency than uridines, which
      explains the presence of adenylated U6 snRNAs in cells lacking Usb1. We
      determined three high-resolution co-crystal structures of Usb1: wild-type Usb1
      bound to the substrate analog adenosine 5'-monophosphate, and an inactive mutant
      bound to RNAs with a 3' terminal adenosine and uridine. These structures, along
      with QM/MM MD simulations of the catalytic mechanism, illuminate the molecular
      basis for preferential deadenylation of U6 snRNA. The extent of Usb1 processing
      is influenced by the secondary structure of U6 snRNA.

PMID- 30215757
TI  - Achieving Mastery of General Surgery Operative Skill in the Army Healthcare
      System.
AB  - Introduction: Operative case volumes for military surgeons are reported to be
      significantly lower than civilian counterparts. Among the concern that this
      raises is an inability of military surgeons to achieve mastery of their craft.
      Material and Methods: Annual surgical case reports were obtained from seven Army
      military treatment facilities (MTF) for 2012-2016. Operative case volume and
      cumulative operative time were calculated for active duty general surgeons and
      for individual MTFs. Subgroup analyses were also performed based upon rank.
      Results were extrapolated to calculate the amount of time it would take to reach
      a cumulative of 10,000 hours of operative time (the a priori definition for
      achieving mastery). Results: One hundred and two active duty general surgeons
      operated at the seven MTFs during the study period and met the inclusion
      criteria. The average surgeon performed 108 +/- 68 cases/year. The average
      surgeon operated 122 +/- 82 hours/year. At this rate, it would take over 80 years
      to reach mastery of surgery. When stratified based upon rank, Majors averaged 113
      +/- 75 hours/year, Lieutenant Colonels averaged 170 +/- 100 hours/year, and
      Colonels averaged 136 +/- 101 hours/year (p < 0.05). When stratified based upon
      individual MTF, surgeons at the busiest facility averaged 187 +/- 103 hours/year
      and those at the least busy facility averaged 85 +/- 56 hours/year (p < 0.05).
      Conclusions: Obtaining mastery of general surgery is a nearly impossible
      proposition given the current care models at Army MTFs. Alternative staffing and
      patient care models should be developed if Army surgeons are to be masters at
      their craft.

PMID- 30215758
TI  - PTSD as a Mediator in the Relationship Between Post-Concussive Symptoms and Pain
      Among OEF/OIF/OND Veterans.
AB  - Introduction: Traumatic brain injury (TBI), pain, and post-traumatic stress
      disorder (PTSD) commonly co-occur in Veteran populations, particularly among
      Veterans returning from the recent conflicts in Iraq and Afghanistan. Extant
      research indicates that both TBI and PTSD can negatively impact pain broadly;
      however, less is known about how these variables impact one another. The current
      study examines the impact of self-reported post-concussive symptoms on both pain
      severity and pain interference among Veterans with PTSD who screened positive for
      a possible TBI, and subsequently, evaluates the potential mediating role of PTSD
      in these relationships. Materials and Methods: Participants were 126 combat
      Veterans that served in Operation Enduring Freedom, Operation Iraqi Freedom, or
      Operation New Dawn who were being evaluated for participation in a multisite
      treatment outcomes study. As part of an initial evaluation for inclusion in the
      study, participants completed several self-report measures and interviews,
      including the Brief Traumatic Brain Injury Screen, Neurobehavioral Symptom
      Inventory, Brief Pain Inventory, and the Clinician Administered PTSD Scale, which
      were utilized in these analyses. Results: For pain severity, greater post
      concussive symptoms significantly predicted increased pain severity with a
      significant indirect effect of post-concussive symptoms on pain severity through
      PTSD (indirect effect = 0.03; 95% confidence interval = 0.0094-0.0526). Similar
      results were found for pain interference (indirect effect = 0.03; 95% confidence
      interval = 0.0075-0.0471). Conclusions: These findings replicate and extend
      previous findings regarding the relationship between TBI, pain, and PTSD. Self
      reported post-concussive symptoms negatively impact both pain severity and pain
      interference among Veterans with probable TBI, and PTSD serves as a mediator in
      these relationships. Clinically, these results highlight the importance of fully
      assessing for PTSD symptoms in Veterans with a history of TBI presenting with
      pain. Further, it is possible that providing effective PTSD treatment to reduce
      PTSD severity may provide some benefit in reducing post-concussive and pain
      symptoms.

PMID- 30215759
TI  - Mental and Physical Health Correlates of Pain Treatment Utilization Among
      Veterans With Chronic Pain: A Cross-sectional Study.
AB  - Introduction: The annual cost of treatment and lost productivity due to chronic
      pain is estimated to be $635 billion within the USA. Self-management treatments
      for chronic pain result in lower health care costs and lower utilization of
      provider-management treatments, such as hospitalization and medication use. The
      current study sought to identify and characterize patient factors and health
      conditions associated with chronic pain treatment utilization to inform ways to
      improve engagement in self-management pain treatment (e.g., applying heat or ice,
      exercising, or practicing relaxation). This study predicted (1) greater pain
      intensity and pain interference would be associated with greater utilization of
      self-management treatments and (2) this association would be moderated by patient
      factors (gender and age) and health comorbidities (anxiety, trauma, depression,
      and sleep disturbance). Materials and Methods: Baseline data from a three-arm
      clinical trial were collected for 127 Veterans seeking treatment for chronic
      pain. Veterans were recruited via clinician referral and medical record review at
      the Veterans Affairs Puget Sound Health Care System, Washington, USA. Results:
      Self-management treatments were more utilized than provider-management
      treatments. Pain intensity and pain interference were not uniquely associated
      with provider-management or self-management treatment utilization after
      controlling for demographics and mental health status. Sleep disturbance
      moderated the relationship between pain interference and provider-management
      treatment utilization. Depression moderated the relationship between pain
      intensity and provider-management treatment utilization. Conclusions: While study
      conclusions may not generalize to all Veteran populations, findings suggest that
      Veterans with chronic pain were more likely to seek provider-management
      treatments when experiencing high-pain interference and high-sleep disturbance.
      In addition, Veterans were more likely to seek provider-management treatments
      when experiencing low-pain intensity and high-depression symptoms.

PMID- 30215760
TI  - How to fold and protect mitochondrial ribosomal RNA with fewer guanines.
AB  - Mammalian mitochondrial ribosomes evolved from bacterial ribosomes by reduction
      of ribosomal RNAs, increase of ribosomal protein content, and loss of guanine
      nucleotides. Guanine is the base most sensitive to oxidative damage. By
      systematically comparing high-quality, small ribosomal subunit RNA sequence
      alignments and solved 3D ribosome structures from mammalian mitochondria and
      bacteria, we deduce rules for folding a complex RNA with the remaining guanines
      shielded from solvent. Almost all conserved guanines in both bacterial and
      mammalian mitochondrial ribosomal RNA form guanine-specific, local or long-range,
      RNA-RNA or RNA-protein interactions. Many solvent-exposed guanines conserved in
      bacteria are replaced in mammalian mitochondria by bases less sensitive to
      oxidation. New guanines, conserved only in the mitochondrial alignment, are
      strategically positioned at solvent inaccessible sites to stabilize the ribosomal
      RNA structure. New mitochondrial proteins substitute for truncated RNA helices,
      maintain mutual spatial orientations of helices, compensate for lost RNA-RNA
      interactions, reduce solvent accessibility of bases, and replace guanines
      conserved in bacteria by forming specific amino acid-RNA interactions.

PMID- 30215761
TI  - Can zinc pollution promote adaptive evolution in plants? Insights from a one
      generation selection experiment.
AB  - Human activities generate environmental stresses that can lead plant populations
      to become extinct. Population survival would require the evolution of adaptive
      responses that increase tolerance to these stresses. Thus, in pseudometallophyte
      species that have colonized anthropogenic metalliferous habitats, the evolution
      of increased metal tolerance is expected in metallicolous populations. However,
      the mechanisms by which metal tolerance evolves remain unclear. In this study,
      parent populations were created from non-metallicolous families of Noccaea
      caerulescens. They were cultivated for one generation in mesocosms and under
      various levels of zinc (Zn) contamination to assess whether Zn in soil represents
      a selective pressure. Individual plant fitness estimates were used to create
      descendant populations, which were cultivated in controlled conditions with
      moderate Zn contamination to test for adaptive evolution in functional traits.
      The number of families showing high fitness estimates in mesocosms was
      progressively reduced with increasing Zn levels in soil, suggesting increasing
      selection for metal tolerance. In the next generation, adaptive evolution was
      suggested for some physiological and ecological traits in descendants of the most
      exposed populations, together with a significant decrease of Zn
      hyperaccumulation. Our results confirm experimentally that Zn alone can be a
      significant evolutionary pressure promoting adaptive divergence among
      populations.

PMID- 30215762
TI  - Efficacy of chimeric ectolysin P128 in drug-resistant Staphylococcus aureus
      bacteraemia in mice.
AB  - Objectives: P128 is a recombinant chimeric ectolysin with potent
      antistaphylococcal activity. P128 was evaluated as monotherapy and in combination
      with two standard-of-care (SoC) antibiotics, vancomycin and daptomycin, in mouse
      models of Staphylococcus aureus bacteraemia. Methods: Healthy BALB/c mice were
      challenged (intraperitoneally) with 109 cfu of MRSA strain COL or USA300 and
      treated with a single dose of P128 (0.2-10 mg/kg). Drug synergy was tested using
      a single dose of P128 (0.2 or 2.5 mg/kg) along with sub-therapeutic dose levels
      of vancomycin (27.5 or 55 mg/kg) or daptomycin (12.5 mg/kg). Bacterial load was
      checked in peritoneal fluid and in blood, at different time intervals. Synergy
      against drug-resistant strains was tested using the P128/vancomycin combination
      against vancomycin-resistant S. aureus (VRSA). Results: In MRSA bacteraemia,
      P128, vancomycin and daptomycin monotherapy resulted in 31%, 46% and 46%
      survival, respectively. The P128/vancomycin and P128/daptomycin combinations
      afforded increased survival of 85% and 88%, respectively. P128 showed a rapid
      bactericidal effect with a reduction of cfu in both the peritoneal fluid and the
      blood within 1 h. In VRSA bacteraemia, a mouse-equivalent therapeutic dose of
      vancomycin (110 mg/kg) failed to rescue animals. P128 (1-20 mg/kg) as monotherapy
      resulted in dose-dependent efficacy. Survival (37%) with 2.5 mg/kg P128 increased
      to 63% with the P128/vancomycin combination. Conclusions: P128 exerted a rapid
      bactericidal effect in vivo and rescued animals from fatal invasive MRSA and VRSA
      infections. P128/SoC antibiotic combinations exerted a synergistic effect. P128
      restored the susceptibility of VRSA to vancomycin. P128 is a novel, potent
      therapeutic agent for antibiotic-resistant, systemic S. aureus infections.

PMID- 30215763
TI  - Temporal Trends in Co-trimoxazole Use Among Children on Antiretroviral Therapy
      and the Impact of Co-trimoxazole on Mortality Rates in Children Without Severe
      Immunodeficiency.
AB  - Background: Co-trimoxazole is recommended for all children with human
      immunodeficiency virus. In this analysis, we evaluate trends in pediatric co
      trimoxazole use and survival on co-trimoxazole in children using antiretroviral
      therapy (ART). Methods: We used data collected between January 1, 2006, and March
      31, 2016, from the International Epidemiology Databases to Evaluate AIDS.
      Logistic regression was used to evaluate factors associated with using co
      trimoxazole at ART initiation. Competing risk regression was used to assess
      factors associated with death. Results: A total of 54113 children were included
      in this study. The prevalence of co-trimoxazole use at ART initiation increased
      from 66.5% in 2006 to a peak of 85.6% in 2010 and then declined to 48.5% in 2015
      2016. A similar trend was observed among children who started ART with severe
      immunodeficiency. After adjusting for year of ART initiation, younger age (odds
      ratio [OR], 1.18 for <1 vs 1 to <5 years of age [95% confidence interval (CI),
      1.09-1.28]), lower height-for-age z score (OR, 1.15 for less than -3 vs greater
      than -2 [95% CI, 1.08-1.22]), anemia (OR, 1.08 [95% CI, 1.02-1.15]), severe
      immunodeficiency (OR, 1.25 [95% CI, 1.18-1.32]), and receiving care in East
      Africa (OR, 8.97 vs Southern Africa [95% CI, 8.17-9.85]) were associated with a
      high prevalence of co-trimoxazole use. Survival did not differ according to co
      trimoxazole use in children without severe immunodeficiency (hazard ratio, 1.01
      for nonusers versus users [95% CI, 0.77-1.34]). Conclusions: Recent declines in
      co-trimoxazole use may not be linked to the current shift toward early ART
      initiation. Randomized trial data might be needed to establish the survival
      benefit of co-trimoxazole in children without severe immunodeficiency.

PMID- 30215764
TI  - AWESOME: a database of SNPs that affect protein post-translational modifications.
AB  - Protein post-translational modifications (PTMs), including phosphorylation,
      ubiquitination, methylation, acetylation, glycosylation et al, are very important
      biological processes. PTM changes in some critical genes, which may be induced by
      base-pair substitution, are shown to affect the risk of diseases. Recently, large
      scale exome-wide association studies found that missense single nucleotide
      polymorphisms (SNPs) play an important role in the susceptibility for complex
      diseases or traits. One of the functional mechanisms of missense SNPs is that
      they may affect PTMs and leads to a protein dysfunction and its downstream
      signaling pathway disorder. Here, we constructed a database named AWESOME (A
      Website Exhibits SNP On Modification Event, http://www.awesome-hust.com), which
      is an interactive web-based analysis tool that systematically evaluates the role
      of SNPs on nearly all kinds of PTMs based on 20 available tools. We also provided
      a well-designed scoring system to compare the performance of different PTM
      prediction tools and help users to get a better interpretation of results. Users
      can search SNPs, genes or position of interest, filter with specific
      modifications or prediction methods, to get a comprehensive PTM change induced by
      SNPs. In summary, our database provides a convenient way to detect PTM-related
      SNPs, which may potentially be pathogenic factors or therapeutic targets.

PMID- 30215765
TI  - Botulinum Toxin as a Novel Treatment for Chronic Exertional Compartment Syndrome
      in the U.S. Military.
AB  - Chronic exertional compartment syndrome (CECS) is a debilitating condition that
      is not uncommon in athletes and military service members. The only curative
      treatment for this condition, surgical fascial release, was first described in
      1956. In the ensuing 62 years, this has remained the standard therapy despite
      symptom recurrence in 45% of military service members who underwent surgery. In
      2013, a case series introduced intracompartmental injections of botulinum toxin A
      as a non-surgical treatment option for CECS, which proved effective in 15 out of
      16 patients. In this case report, we present the case of a U.S. military service
      member treated with BoNT-A for bilateral lower leg CECS. This patient remains
      pain free at 11 months after initial treatment. This case, coupled with
      previously published cases series, demonstrates the potential of this novel
      treatment as a long-term, non-surgical alternative for CECS in the U.S. military
      population.

PMID- 30215766
TI  - CRISPR-Cap: multiplexed double-stranded DNA enrichment based on the CRISPR
      system.
AB  - Existing methods to enrich target regions of genomic DNA based on PCR,
      hybridization capture, or molecular inversion probes have various drawbacks,
      including long experiment times and low throughput and/or enrichment quality. We
      developed CRISPR-Cap, a simple and scalable CRISPR-based method to enrich target
      regions of dsDNA, requiring only two short experimental procedures that can be
      completed within two hours. We used CRISPR-Cap to enrich 10 target genes 355.7
      fold on average from Escherichia coli genomic DNA with a maximum on-target ratio
      of 81% and high enrichment uniformity. We also used CRISPR-Cap to measure gene
      copy numbers and detect rare alleles with frequencies as low as 1%. Finally, we
      enriched coding sequence regions of 20 genes from the human genome. We envision
      that CRISPR-Cap can be used as an alternative to other widely used target
      enrichment methods, which will broaden the scope of CRISPR applications to the
      field of target enrichment field.

PMID- 30215767
TI  - Effect of Urinary Sheath Use on Hydration Status of Fighter Pilots Under Severe
      Thermal Stress: An Observational Study.
AB  - Introduction: Fighter jet pilots may adopt a voluntary hypohydration strategy
      hours before take-off to avoid urinating in flight. This may favor sortie-induced
      dehydration and potentially increase flying errors. Since 2015, French pilots
      have used a urinary sheath (US) that appears to have resolved this problem.
      However, its effect has never been assessed. Methods: Urine specific gravity
      (USG) before and after sorties, inflight intake (water and food) and loss (sweat
      and urine), and changes in bodyweight were measured during 44 long (~370 minutes)
      sorties (22 in 2015 without a US, No-US group, and 22 in 2017 with a US, US
      group). Results: The USG before sorties was lower in the US than No-US group
      (1.019 +/- 0.008 vs 1.028 +/- 0.006, p = 0.008) and the proportion of
      hypohydrated pilots (>1.020) was lower in the US than No-US group (29 vs 90%, p =
      0.007). Total loss and intake were higher in the US group (1,793 +/- 640 and 927
      +/- 585 g, respectively) than in the No-US group (1,337 +/- 382 and 359 +/- 191
      g, respectively; p < 0.006). Changes in bodyweight, both absolute (-977 +/- 367 g
      for the No-US and -866 +/- 593 g for the US group) and relative (1.16 +/- 0.51%
      for the No-US and 1.13 +/- 0.77% for the US group) during sorties were not
      altered by wearing a US. Conclusion: The use of a US successfully mitigates
      preflight dehydration, as reflected by decreases in USG, showing that pilots, at
      least partially, abandon preflight voluntary hypohydration strategies. It also
      favored water and food intake during flight without enhancing inflight
      dehydration, shown by the parallel increases in loss (urine and sweat) when
      wearing a US.

PMID- 30215768
TI  - OEF/OIF/OND Veterans Seeking PTSD Treatment: Perceptions of Partner Involvement
      in Trauma-Focused Treatment.
AB  - Introduction: Post-traumatic stress disorder (PTSD) has been linked to a variety
      of adverse mental and physical health outcomes including distressed
      relationships. Involving romantic partners in PTSD treatment appears to be a
      promising new avenue for PTSD treatment; however, additional research is
      necessary to clarify veteran preferences for inclusion of significant others in
      treatment and relationship characteristics that may influence such preferences.
      Accordingly, the present study was designed to evaluate Operation Enduring
      Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) veterans' desire
      to include romantic partners in trauma-focused care (n = 74) and to explore
      psychological and relationship variables associated with preference for partner
      inclusion in PTSD treatment. Materials and Methods: This study surveyed male (N =
      74) OEF/OIF/OND combat veterans seeking mental health services at a Veterans
      Health Administration PTSD treatment program. Relationships between PTSD
      symptoms, romantic relationship functioning, and interest in including their
      romantic partner in PTSD treatment were examined. Results: Consistent with
      previous research, OEF/OIF/OND veterans seeking treatment at a specialty PTSD
      program report low relationship satisfaction. The majority of participants
      reported that PTSD symptoms interfere with relationship functioning;
      specifically, numbing symptoms were a significant predictor of PTSD-related
      relationship impairment. A minority (26%) of participants reported a desire to
      include their romantic partner in PTSD treatment. Greater behavioral avoidance
      and communication difficulties were associated with increased interest in
      including a romantic partner in PTSD treatment. Conclusion: We confirmed that
      OEF/OIF/OND veterans seeking PTSD treatment experience PTSD-related problems in
      romantic relationships, low-relationship satisfaction, and relationship
      satisfaction was positively associated with perceived communication and problem
      solving skills. A minority of veterans were interested in involving significant
      others in their PTSD treatment; however, in the present study, veterans were not
      given information about the various ways that a romantic partner might be
      involved in treatment, and they were not presented with specific conjoint
      therapies (e.g., Cognitive-Behavioral Conjoint Therapy for PTSD, Strategic
      Approach Therapy). For veterans with PTSD, relationship distress, and
      communication difficulties, conjoint psychotherapies may offer a way of
      increasing engagement in PTSD treatment by parsimoniously addressing multiple
      treatment targets at once (PTSD symptoms, relationship distress, communication
      problems) and providing veteran-centered care.

PMID- 30215769
TI  - A multilinguistic analysis of spelling among children with cochlear implants.
AB  - This study examines the spelling of nine elementary school children with cochlear
      implants (CIs) who use spoken language, and compares their performance with
      children who have typical hearing and children who are hard of hearing (HH).
      Compared to children with typical hearing, children with CIs did not produce a
      significantly different percentage of misspelled words (p = 0.431, d = 0.38), but
      their spelling errors comprised significantly lower percentages of homophone
      substitutions (p = 0.019, r = 0.61) and legal vowel errors (p = 0.011, r = 0.61).
      Children with CIs and children who are HH did not produce a significantly
      different percentage of misspelled words (p = 0.521, d = 0.31) or a significantly
      different distribution of categorical spelling errors. Results suggest that
      children with CIs utilize similar linguistic strategies as their peers who are HH
      but different strategies than peers with typical hearing when attempting to spell
      unfamiliar words.

PMID- 30215770
TI  - Pharmacokinetics and pharmacogenomics of mycophenolic acid and its clinical
      correlations in maintenance immunosuppression for lupus nephritis.
AB  - Background: There is little data on mycophenolic acid (MPA) pharmacokinetics and
      pharmacogenomics and optimal MPA exposure in lupus nephritis (LN) patients during
      long-term maintenance. Methods: We measured blood MPA levels at 1, 2, 4, 8, 10
      and 12-h post-dose (i.e. C1, C2, C4, C8, C10 and C12) in 88 stable LN patients
      receiving maintenance prednisolone and mycophenolate mofetil, repeated every 6
      months. The relationship between MPA exposure and single nucleotide polymorphisms
      (SNPs) of adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2;
      rs2273697, rs3740066, rs717620 and rs17222723), organic anion-transporting
      polypeptides (OATPs; rs7311358 and rs4149117) and uridine diphosphate
      glucuronosyltransferase (UGT; rs17863762, rs6714486, rs17868320 and rs72551330)
      was also investigated. Results: C1, C2 and C12 were 8.3 +/- 6.6 , 7.2 +/- 5.2 and
      2.0 +/- 1.4 mg/L and all correlated with the 12-h area under the curve (AUC0-12;
      r = 0.51, 0.85 and 0.73; P = 0.02, <0.001 and <0.001, respectively). C12
      inversely correlated with hemoglobin, immunoglobulins and leukocyte levels (P <
      0.05 for all). Five renal flares, 11 episodes of infection and 10 episodes of
      anemia (hemoglobin <10 g/dL) occurred over 96 weeks, with a corresponding C12 of
      1.3 +/- 0.5, 4.3 +/- 2.6 and 2.9 +/- 1.5 mg/L, respectively (versus 2.4 +/- 1.2,
      1.8 +/- 1.2 and 1.7 +/- 1.1 mg/L in patients without these complications; P =
      0.041, <0.001 and 0.004). SNP rs2273697 A/G in the ABCC2 gene was associated with
      lower MPA exposure compared with G/G (1075.9 +/- 239.9 versus 1891.5 +/- 918.9
      mgh/L per g/kg; P = 0.003). SNPs of OATP and UGT were unrelated to MPA level.
      Conclusion: MPA C12 correlates with the AUC0-12 and is related to renal flare,
      infection and anemia. SNP rs2273697 A/G is associated with lower MPA exposure.

PMID- 30215771
TI  - Validation and Cross-Reactivity Data for Fentanyl Analogs With the Immunalysis
      Fentanyl ELISA.
AB  - Every year new fentanyl analog compounds, or fentanyls, appear on the drug scene.
      Development of immunoassays dedicated for screening individual molecules is
      challenging due to the short-lived presence of these compounds on the
      recreational drug market. Therefore, we investigated the detecting capabilities
      of the immunalysis fentanyl direct enzyme-linked immunosorbent assay (ELISA) kit
      against fentanyl in whole blood, and determined the cross-reactivity of nine
      fentanyl analogs (2-fluorofentanyl, acetylfentanyl, acrylfentanyl, carfentanil,
      cyclopropylfentanyl, tetrahydrofuranylfentanyl, furanylfentanyl, ocfentanil,
      valerylfentanyl) to confirm its validity for the general screening of fentanyls.
      Immunalysis ELISA assay was used to test whole blood samples fortified with
      fentanyl on a TECAN Freedom EVOlyzer platform, according to manufacturer
      specifications. The kit successfully was validated for fentanyl screening with a
      cutoff set at 0.5 ng/mL, and all tested analogs, with the exclusion of
      carfentanil, were detected. The lowest cross-reactivity with the kit was obtained
      with furanylfentanyl (20% +/- 1, 95% confidence intervals (CI)) and 4
      fluoroisobutyrfentanyl (25% +/- 1, 95% CI), while the highest was recorded using
      acetylfentanyl (99% +/- 11, 95% CI) and acrylfentanyl (94% +/- 10, 95% CI). Post
      mortem samples containing fentanyl, acrylfentanyl, cyclopropylfentanyl, THF
      fentanyl and 4-fluoroisobutyrfentanyl were screened, and sensitivity and
      specificity of each analog were calculated. Positive screening results were
      generated by all post-mortem cases containing fentanyl (n = 14), acrylfentanyl (n
      = 11), cyclopropylfentanyl (n = 14), tetrahydrofuranylfentanyl (n = 13) and 4
      fluoroisobutyrfentanyl (n = 10). Concentration of post-mortem fentanyl samples
      ranged from 0.5 ng/mL (cutoff) to 230 ng/mL, while the range for analogs was 3.4
      36 ng/mL (cyclopentylfentanyl), 0.76-370 ng/mL (4-fluoroisobutyrfentanyl), 0.02
      12 ng/mL (acrylfentanyl) and 2-26 ng/mL (tetrahydrofuranylfentanyl). The
      immunalysis fentanyl direct ELISA kit was successfully validated and showed
      significant cross-reactivity for all tested fentanyls, except carfentanil, making
      it a suitable technique for fentanyl and fentanyl analogs screening.

PMID- 30215772
TI  - Growth-restricting effects of siRNA transfections: a largely deterministic
      combination of off-target binding and hybridization-independent competition.
AB  - Perturbation of gene expression by means of synthetic small interfering RNAs
      (siRNAs) is a powerful way to uncover gene function. However, siRNA technology
      suffers from sequence-specific off-target effects and from limitations in knock
      down efficiency. In this study, we assess a further problem: unintended effects
      of siRNA transfections on cellular fitness/proliferation. We show that the
      nucleotide compositions of siRNAs at specific positions have reproducible growth
      restricting effects on mammalian cells in culture. This is likely distinct from
      hybridization-dependent off-target effects, since each nucleotide residue is seen
      to be acting independently and additively. The effect is robust and reproducible
      across different siRNA libraries and also across various cell lines, including
      human and mouse cells. Analyzing the growth inhibition patterns in correlation to
      the nucleotide sequence of the siRNAs allowed us to build a predictor that can
      estimate growth-restricting effects for any arbitrary siRNA sequence. Competition
      experiments with co-transfected siRNAs further suggest that the growth
      restricting effects might be linked to an oversaturation of the cellular miRNA
      machinery, thus disrupting endogenous miRNA functions at large. We caution that
      competition between siRNA molecules could complicate the interpretation of double
      knockdown or epistasis experiments, and potential interactions with endogenous
      miRNAs can be a factor when assaying cell growth or viability phenotypes.

PMID- 30215773
TI  - Management of children with congenital nephrotic syndrome: challenging treatment
      paradigms.
AB  - Background: Management of children with congenital nephrotic syndrome (CNS) is
      challenging. Bilateral nephrectomies followed by dialysis and transplantation are
      practiced in most centres, but conservative treatment may also be effective.
      Methods: We conducted a 6-year review across members of the European Society for
      Paediatric Nephrology Dialysis Working Group to compare management strategies and
      their outcomes in children with CNS. Results: Eighty children (50% male) across
      17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55;
      NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in
      WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S
      albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following
      unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a
      reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at
      bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared
      between two groups of NPHS1 patients: those who underwent bilateral nephrectomies
      (n = 25) versus those on conservative management (n = 17). The number of septic
      or thrombotic episodes and growth were comparable between the groups. The
      response to antiproteinuric treatment, as well as renal and patient survival, was
      independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20
      (80%) children in the nephrectomy group were transplanted and 1 died. In the
      conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were
      transplanted and 2 died. Conclusion: An individualized, stepwise approach with
      prolonged conservative management may be a reasonable alternative to early
      bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations.
      Further prospective studies are needed to define indications for unilateral
      nephrectomy.

PMID- 30215774
TI  - The application of commercially available mobile cigarette topography devices for
      e-cigarette vaping behavior measurements.
AB  - Introduction: The ability to reliably measure real-world vaping behavior is
      critical to understand exposures to potential toxins. Commercially available
      mobile topography devices were originally designed to measure cigarette puffing
      behavior. Information regarding how applicable these devices are to the
      measurement of e-cigarette vaping topography is needed. Methods: CReSS (Pocket)
      and SPA-M mobile topography devices were tested against the calibrated laboratory
      based SPA-D device combined with an analytical smoking machine that generates
      programmable puffs with high precision. E-cigarettes' puff topography was
      measured over a range of puff volumes (10-130 mL) at 2 and 5 seconds puff
      durations (using bell and square shaped puffs). "Real-world" topography data
      collected from 10 participants during one week of at-home vaping was also
      analyzed. Recording anomalies and limitations of the devices such as accuracy of
      detection of the puff end, flow rate drop-outs, unreported puffs, and abandoned
      vaping sessions for the CReSS; and multi-peak puffs for the SPA-M were defined.
      Results: The accuracy of puff volumes and durations was determined for both
      devices. The error for SPA-M was generally within +/-10%, while that for the
      CReSS varied more widely. The CReSS consistently underestimated puff duration at
      higher flow rates. Conclusions: CReSS and SPA-M mobile topography devices can be
      used for real-world e-cigarette topography measurements, but researchers have to
      be aware of the limitations. Both devices can provide accurate measurements only
      under certain puff parameter ranges. The SPA-M provided more accurate
      measurements under a wider range of puffing parameters than the CReSS. Summary
      data reported by both devices require thorough analysis of the raw data to avoid
      misleading data interpretation. Implications: Results of this study provide
      researchers with valuable information about the capability of commercially
      available cigarette topography devices to measure real-world vaping behaviors.
      The differing measurement ranges of the two devices and puff recording
      limitations and anomalies should be taken into account during analysis and
      interpretation of real-world data.

PMID- 30215775
TI  - Diagnosing Pemphigus Foliaceus: A Rare Blistering Disease Masquerading as a
      Common Dermatologic Disorder.
AB  - Pemphigus foliaceus (PF) is an autoimmune dermatologic disease that typically
      presents with painful, superficial blisters that evolve into scaling erosions in
      a seborrheic distribution. This case study intends to demonstrate that due to the
      relative scarcity of the disease and its distribution on the body, PF can easily
      be misdiagnosed. We present a 43-year-old African American male that presented to
      the dermatology clinic with an 18-month history of non-pruritic, violaceous,
      scaling patches and plaques most prominent on the malar cheeks, upper chest and
      upper back. He had been evaluated at an outside hospital with a high suspicion
      for cutaneous lupus erythematosus (CLE) and seborrheic dermatitis. However,
      repeated biopsies revealed non-specific spongiotic dermatitis, not consistent
      with CLE or seborrheic dermatitis. Over the subsequent months, he received
      treatment for both conditions without improvement in his symptoms. When he was
      referred to our dermatology clinic, repeat biopsies were obtained which
      demonstrated acantholysis and dyskeratosis in the granular layer, consistent with
      PF. Direct immunofluorescence revealed intercellular IgG staining most prominent
      in the epidermis, also consistent with PF. Finally, enzyme-linked immunosorbent
      assay for anti-desmoglein 1 returned positive, confirming the diagnosis. Upon
      review of the previous biopsies, focal areas of acantholysis and dyskeratosis
      were noted in the granular layer, which would have pointed away from a diagnosis
      of CLE or seborrheic dermatitis if PF was included in the clinical differential
      diagnosis. This case serves as a reminder that when there is a discrepancy in
      clinical-pathologic correlation, it is important to revisit the case and consider
      other pathologies.

PMID- 30215776
TI  - Topokaryotyping demonstrates single cell variability and stress dependent
      variations in nuclear envelope associated domains.
AB  - Analysis of large-scale interphase genome positioning with reference to a nuclear
      landmark has recently been studied using sequencing-based single cell approaches.
      However, these approaches are dependent upon technically challenging, time
      consuming and costly high throughput sequencing technologies, requiring
      specialized bioinformatics tools and expertise. Here, we propose a novel,
      affordable and robust microscopy-based single cell approach, termed
      Topokaryotyping, to analyze and reconstruct the interphase positioning of genomic
      loci relative to a given nuclear landmark, detectable as banding pattern on
      mitotic chromosomes. This is accomplished by proximity-dependent histone
      labeling, where biotin ligase BirA fused to nuclear envelope marker Emerin was
      coexpressed together with Biotin Acceptor Peptide (BAP)-histone fusion followed
      by (i) biotin labeling, (ii) generation of mitotic spreads, (iii) detection of
      the biotin label on mitotic chromosomes and (iv) their identification by
      karyotyping. Using Topokaryotyping, we identified both cooperativity and
      stochasticity in the positioning of emerin-associated chromatin domains in
      individual cells. Furthermore, the chromosome-banding pattern showed dynamic
      changes in emerin-associated domains upon physical and radiological stress. In
      summary, Topokaryotyping is a sensitive and reliable technique to quantitatively
      analyze spatial positioning of genomic regions interacting with a given nuclear
      landmark at the single cell level in various experimental conditions.

PMID- 30215777
TI  - Nrf2 Activation Ameliorates Hepatotoxicity Induced by a Heme Synthesis Inhibitor.
AB  - Transcription factor Nrf2 protects hepatocytes against various toxicants by
      upregulating cytoprotective genes. The heme synthesis inhibitor 3,5
      diethoxycarbonyl-1,4-dihydrocollidine (DDC) leads to liver injury around the
      portal vein, unlike other groups of toxicants that cause hemorrhage and necrosis
      in the centrilobular area. To examine whether and how Nrf2 protects livers from
      the injury, we fed DDC to Nrf2 knockout (Nrf2KO), wild-type (WT), Keap1flox/flox
      (Keap1-knockdown; Keap1KD), and liver-specific Keap1 knockout (Keap1-Alb) mice,
      as these lines of mice exhibit stepwise increases in Nrf2 protein expression
      levels. Liver-specific Keap1::Nrf2 double-knockout (Keap1::Nrf2-Alb) mice were
      also exploited to examine the contribution of Nrf2. Two weeks after DDC-feeding,
      Keap1-Alb mice were fully recovered from body-weight-loss, but the WT and Nrf2KO
      mice were not. The liver-to-body-weight ratio of Keap1-Alb mice was significantly
      larger than that of WT and Nrf2KO mice. Two indicators of hepatotoxicity, alanine
      aminotransferase and bilirubin in plasma, were both elevated in WT mice, but
      downregulated in Keap1-Alb mice after the DDC-feeding. DDC-induced porphyrin
      accumulation was reduced in the livers of Keap1-Alb and Keap1KD mice compared
      with that of WT mice. When assessed by the Nqo1 level, Nrf2 expression was
      further enhanced by DDC in Keap1-Alb mice, suggesting that DDC may have a Keap1
      independent potential to activate Nrf2. Genetic activation of Nrf2 in Keap1-Alb
      mice increased the extracellular excretion of porphyrins, but contrary to our
      expectation, hepatic damages in Nrf2KO mice appeared to be similar to that of WT
      mice. Based on these observations, we conclude that Nrf2 activation protects
      livers against DDC-elicited hepatotoxicity.

PMID- 30215778
TI  - Use of Immersive Learning and Simulation Techniques to Teach and Research Opioid
      Prescribing Practices.
AB  - Introduction: Unsafe opioid prescribing practices to treat acute and chronic pain
      continue to contribute to the opioid overdose crisis in the United States, a
      growing public health emergency that harms patients and their communities. Poor
      opioid prescribing practices stem in part from a lack of education and skills
      training surrounding pain and opioid management. Methods: As part of the Clinical
      Pain Medicine Fellowship at Stanford University, physicians were given the
      opportunity to participate in a pilot program to practice opioid management in a
      live, simulated interaction. Twenty-seven physician trainees participated in the
      simulation with a live, standardized patient actor. Before beginning the
      simulation, participants were given a detailed patient history that included the
      patient's risk for opioid abuse. They were also provided with relevant risk
      evaluation and mitigation (REM) tools. All simulation interactions were video
      recorded and coded by two independent reviewers. A detailed coding scheme was
      developed before video analysis, and an inter-rater reliability score showed
      substantial agreement between reviewers. Results: Contrary to expectations, many
      of the observed performances by trainees contained aspects of unsafe opioid
      prescribing, given the patient history. Many trainees did not discuss their
      patient's aberrant behaviors related to opioids or the patient's risk for opioid
      abuse. Marked disparities were also observed between the trainees' active patient
      interactions and their written progress notes. Discussion: This simulation
      addresses a pressing need to further educate, train, and provide point-of-care
      tools for providers prescribing opioids. We present our experience and
      preliminary findings.

PMID- 30215780
TI  - Optimizing peri-operative care to prevent acute kidney injury.

PMID- 30215779
TI  - Caffeine consumption and mortality in chronic kidney disease: a nationally
      representative analysis.
AB  - Background: An inverse relationship between coffee consumption and mortality has
      been reported in the general population. However, the association between
      caffeine consumption and mortality in patients with chronic kidney disease (CKD)
      remains uncertain. Methods: We analysed 4863 non-institutionalized USA adults
      with CKD [defined by an estimated glomerular filtration rate (eGFR) of 15-60
      mL/min/1.73 m2 and/or a urinary albumin:creatinine ratio >30 mg/g] in a
      nationwide study using the National Health and Nutrition Examination Survey
      (NHANES) 1999-2010. Caffeine consumption was evaluated by 24-h dietary recalls at
      baseline and all-cause, cardiovascular and cancer mortality were evaluated until
      31 December 2011. We also performed an analysis of caffeine consumption according
      to its source (coffee, tea and soft drinks). Quartiles of caffeine consumption
      were <28.2 mg/day (Q1), 28.2-103.0 (Q2), 103.01-213.5 (Q3) and >213.5 (Q4).
      Results: During a median follow-up of 60 months, 1283 participants died.
      Comparing with Q1 of caffeine consumption, the adjusted hazard ratio for all
      cause mortality was 0.74 [95% confidence interval (CI) 0.60-0.91] for Q2, 0.74
      (95% CI 0.62-0.89) for Q3 and 0.78 (95% CI 0.62-0.98) for Q4 (P = 0.02 for trend
      across quartiles). There were no significant interactions between caffeine
      consumption quartiles and CKD stages or urinary albumin:creatinine ratio
      categories regarding all-cause mortality. Conclusions: We detected an inverse
      association between caffeine consumption and all-cause mortality among
      participants with CKD.

PMID- 30215781
TI  - Improved Dose Estimates for Fluoroscopically Guided Lumbar Epidural Injections.
AB  - Objective: The goal of the study was to determine the potential impact of system
      inaccuracies and table attenuation on fluoroscope-reported dose values. Design:
      An Institutional Review Board-approved study was conducted to collect detailed
      acquisition and patient exposure data for fluoroscopy-guided lumbar epidural
      injections. Background: System-reported dosimetry values, especially the air
      Kinetic Energy Released per unit MAss and dose-area product metrics, are
      routinely used for estimating the radiation burden to patients undergoing
      fluoroscopy-guided procedures. However, these metrics do not account for other
      factors, such as acquisition geometry, where the table may attenuate a
      substantial fraction of the x-ray intensity, and system dosimetry inaccuracies,
      which are only required to be accurate within +/-35%. Methods: Acquisition data
      from 46 patients undergoing fluoroscopy-guided lumbar epidural injections were
      collected to better estimate the true incident dose-area product. Gantry angles,
      x-ray technique factors, and field sizes were collected to characterize each
      procedure. Additionally, the fluoroscope dosimetry accuracy and table attenuation
      properties were evaluated as a function of kVp to generate the correction factors
      necessary for accurate dosimetry estimates. Results: The system-reported values
      overestimated the total patient entrance dose-area product by an average of 34%
      (13-44%). Errors may be substantially higher for systems with less accurate
      fluoroscopes or more anterior-posterior projections. Correcting system-reported
      dosimetry values for systematic inaccuracies and variability can substantially
      improve fluoroscopic dose values. Conclusions: Including corrections for system
      output inaccuracies and acquisition factors such as table attenuation is
      necessary for any reliable assessment of radiation burden to patients associated
      with fluoroscopy-guided procedures.

PMID- 30215782
TI  - Restored Self: A Phenomenological Study of Pain Relief by Cannabis.
AB  - Objective: To explore the subjective experience of pain relief by cannabis.
      Design: Qualitative data were collected through in-depth semistructured
      interviews. Interview transcripts were analyzed using interpretative
      phenomenological analysis (IPA). Subjects: Nineteen patients, aged 28 to 79, who
      were treated with medical cannabis under the supervision of a pain clinic in
      Israel. Results: Three key themes that emerged from the analysis were explored:
      1) the Sigh of Relief, describing the corporal sensation of using cannabis,
      including a sense of relaxation and reduction in pain; 2) the Return to
      Normality, describing the comprehensive effect of using cannabis, including an
      increased ability to sleep, focus, and function; and 3) the Side Effects of using
      cannabis. Conclusions: We propose the term Restored Self to conceptualize the
      effect of medical cannabis. Restored Self is the experience of regaining one's
      sense of self, sense of normality, and sense of control over one's life.

PMID- 30215783
TI  - Linking Cortical and Connectional Pathology in Schizophrenia.
AB  - Schizophrenia is associated with cortical thickness (CT) deficits and breakdown
      in white matter microstructure. Whether these pathological processes are related
      remains unclear. We used multimodal neuroimaging to investigate the relationship
      between regional cortical thinning and breakdown in adjacent infracortical white
      matter as a function of age and illness duration. Structural magnetic resonance
      and diffusion images were acquired in 218 schizophrenia patients and 167 age
      matched healthy controls to map CT and fractional anisotropy in regionally
      adjacent infracortical white matter at various cortical depths. We found a robust
      and reproducible relationship between thickness and anisotropy deficits, which
      were inversely correlated across cortical regions (r = -.5, P < .0001): the most
      anisotropic infracortical white matter was found adjacent to regions with
      extensive cortical thinning. This pattern was evident in early (20 y: r = -.3, P
      = .005) and middle life (30 y: r = -.4, P = .004, 40 y: r = -.3, P = .04), but
      not beyond 50 years (P > .05). Frontal pathology contributed most to this
      pattern, with cortical thinning in patients compared to controls at all ages (P <
      .05); in contrast to initially elevated frontal white matter anisotropy in
      patients at 30 years, followed by rapid white matter decline with age (rate of
      annual decline; patients: 0.0012, controls 0.0006, P < .001). Our findings point
      to pathological dependencies between gray and white matter in a large sample of
      schizophrenia patients. We argue that elevated frontal anisotropy reflects
      regionally-specific, compensatory responses to cortical thinning, which are
      eventually overwhelmed with increasing illness duration.

PMID- 30215785
TI  - Extended Nicotine Patch Treatment among Smokers With and Without Comorbid
      Psychopathology.
AB  - Introduction: Individuals with psychiatric conditions smoke at higher rates than
      the general population and may need more intensive treatment to quit. We examined
      whether or not extended treatment with nicotine patch, combined with behavior
      counseling, would disproportionally benefit smokers with versus without a
      lifetime psychiatric condition. Methods: We conducted secondary data analysis of
      data from an effectiveness trial of treatment with 12 counseling sessions (48
      weeks) and 21-mg nicotine patch (8, 24, or 52 weeks) among 525 adult daily
      smokers (Schnoll et al 2015 JAMA Intern Med). A structured clinical interview
      assessed past and current DSM-IV psychiatric disorders (major depression,
      generalized anxiety disorder, alcohol abuse/dependence, and substance
      abuse/dependence). Abstinence was bioverified at Week 52. Logistic regression
      evaluated the effect of the psychiatric status by treatment duration interaction
      on abstinence at Week 52, covarying for sociodemographics, baseline psychological
      symptoms, and treatment adherence. Results: At baseline, 115 (21.9%) participants
      were diagnosed with one or more psychiatric conditions. The psychiatric status by
      treatment duration interaction was significant for Week 52 abstinence (p=.027).
      Abstinence rates between smokers with versus without a psychiatric condition in
      the 24-week treatment arm (9.3% vs. 31.5% abstinent) significantly differed from
      the 8-week treatment arm (18.8% vs. 22.3%), p=.017. Abstinence rates for smokers
      with (22.5%) versus without a psychiatric condition (19.7%) in the 52-week
      treatment arm did not differ from the 8-week arm. Conclusions: Targeted smoking
      cessation treatment, rather than extending treatment duration, may be especially
      warranted to optimize treatment for smokers with comorbid mood, anxiety, and
      substance use disorders.

PMID- 30215786
TI  - X-RAY EMISSION FROM MATERIALS PROCESSING LASERS.
AB  - The emission of laser induced X-rays from materials processing ultra-short pulsed
      laser systems was measured. The absolute spectral photon fluence was determined
      using a thermoluminescence detector based few-channel spectrometer. The spectra
      at 10 cm from the laser focus were in the energy region between 2 and 25 keV with
      mean energies of ~4-6 keV (when weighted by fluence or directional dose
      equivalent) and up to 13 keV (when weighted by ambient dose equivalent). The
      operational quantities, H.'(0.07), H.'(3) and H.*(10), were determined to be in
      the order of 1600-7300, 16-71 and 1-4 mSv per hour processing time, respectively,
      depending on the material and condition of the workpiece. The dose contribution
      due to photons above 30 keV was for all quantities negligible, i.e. below 10-3.

PMID- 30215784
TI  - Altered Brain Activation During Memory Retrieval Precedes and Predicts Conversion
      to Psychosis in Individuals at Clinical High Risk.
AB  - Memory deficits are a hallmark of psychotic disorders such as schizophrenia.
      However, whether the neural dysfunction underlying these deficits is present
      before the onset of illness and potentially predicts conversion to psychosis is
      unclear. In this study, we investigated brain functional alterations during
      memory processing in a sample of 155 individuals at clinical high risk (including
      18 subjects who later converted to full psychosis) and 108 healthy controls drawn
      from the second phase of the North American Prodrome Longitudinal Study (NAPLS
      2). All participants underwent functional magnetic resonance imaging with a
      paired-associate memory paradigm at the point of recruitment and were clinically
      followed up for approximately 2 years. We found that at baseline, subjects at
      high risk showed significantly higher activation during memory retrieval in the
      prefrontal, parietal, and bilateral temporal cortices (PFWE < .035). This effect
      was more pronounced in converters than nonconverters and was particularly
      manifested in unmedicated subjects (P < .001). The hyperactivation was
      significantly correlated with retrieval reaction time during scan in converters
      (P = .009) but not in nonconverters and controls, suggesting an exaggerated
      retrieval effort. These findings suggest that hyperactivation during memory
      retrieval may mark processes associated with conversion to psychosis, and such
      measures have potential as biomarkers for psychosis prediction.

PMID- 30215788
TI  - Corrigendum to "Current Availability of Stem Cell-Based In Vitro Methods for
      Developmental Neurotoxicity (DNT) Testing".

PMID- 30215787
TI  - MODIFICATION INDUCED BY PROTON IRRADIATION IN BAYFOL UV1 7-2 NUCLEAR TRACK
      DETECTOR.
AB  - Bayfol is a class of polymeric solid state nuclear track detector which has many
      applications in various radiation detection fields. It is a Makrofol
      polycarbonate/polyester blend. Samples from Bayfol film have been irradiated with
      different fluences (1011-1014 p/cm2) of 1 MeV protons at the University of Surrey
      Ion Beam Center, UK. The resultant effect of proton irradiation on the structural
      and optical properties of the Bayfol samples has been investigated using X-ray
      diffraction, Fourier Transform Infrared and UV spectroscopy. The optical energy
      gap was decreased from 4.24 to 4.03 eV with increasing the proton fluence from
      1011 to 1013 p/cm2, and was accompanied by an increase in the Urbach energy from
      0.79 to 1.29 eV. This could be correlated to the results obtained from XRD and
      FTIR spectroscopy. Further, the non-irradiated Bayfol is nearly colorless. It
      showed significant sensitivity to color by proton irradiation, associated with an
      increase in the red and yellow color components. The variation of optical and
      color parameters with the proton fluence indicate that the dynamic range of
      Bayfol UV1 7-2 is in the fluence range from 1011 to 1013 p/cm2.

PMID- 30215789
TI  - The integrated stress response regulates cell health of cardiac progenitors.
AB  - The discovery of mammalian cardiac progenitor cells has suggested that the heart
      consists of not only terminally differentiated beating cardiomyocytes, but also a
      population of self-renewing stem cells with the potential to generate new
      cardiomyocytes (Anderson, Self et al. 2007; Bearzi, Rota et al. 2007; Wu, Chien
      et al. 2008). A consequence of longevity is continual exposure to environmental
      and xenobiotic stresses, and recent literature suggests that hematopoietic stem
      cell pools tightly control cell health through upregulation of the integrated
      stress response and consequent cellular mechanisms such as apoptosis. However,
      whether or not this biological response is conserved in progenitor cells for
      later lineages of tissue specific stem cells is not well understood. Using human
      induced pluripotent stem cells (iPSC) of both cardiac progenitor and mature
      cardiomyocyte lineages, we found that the integrated stress response was
      upregulated in the iPSC cardiac progenitors leading to an increased sensitivity
      for apoptosis relative to the mature cardiomyocytes. Of interest, C/EBP
      homologous protein (CHOP) signaling plays a mechanistic role in the cell death
      phenotype observed in iPSC progenitors, by which depletion of CHOP prevents cell
      death following cellular stress by thapsigargin exposure. Our studies suggest
      that the integrated stress response plays a unique role in maintaining iPSC
      cardiac progenitor cellular integrity by removing unhealthy cells via apoptosis
      following environmental and xenobiotic stresses, thus preventing differentiation
      and self-renewal of damaged cells.

PMID- 30215790
TI  - Treatment Choice for Primary Rectal MALT lymphoma.

PMID- 30215791
TI  - Merits and caveats of propensity scores to adjust for confounding.
AB  - Proper adjustment for confounding is essential when estimating the effects of
      treatments or risk factors on health outcomes in observational data. To this end,
      various statistical methods have been developed. In the past couple of years, the
      use of propensity scores (PSs) to control for confounding has increased. Proper
      understanding of this method is necessary to critically appraise research in
      which it is applied. In this article, we provide an overview of PS methods,
      explaining their concept, advantages and possible disadvantages. Furthermore, the
      use of PS matching, PS adjustment and PS weighting is illustrated using data from
      the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) cohort of
      dialysis patients.

PMID- 30215792
TI  - Fatty-Acid Binding Protein 4 (FABP4) as a Potential Preclinical Biomarker of Drug
      Induced Kidney Injury.
AB  - Identification of improved translatable biomarkers of nephrotoxicity is an unmet
      safety biomarker need. Fatty-acid-binding protein 4 (FABP4) was previously found
      to be associated with clinical renal dysfunction and was proposed as a biomarker
      of glomerular damage. The aim of this study was to evaluate FABP4 as a potential
      preclinical biomarker of drug-induced kidney injury (DIKI). Han-Wistar rats were
      dosed with cisplatin [2.5 mg/kg, single, intraperitoneally (i.p.)], puromycin (10
      mg/kg, daily, i.p.) or N-phenylanthranylic acid [NPAA, 500 mg/kg, daily, per os
      (p.o.)] over a 28-day period to induce proximal tubule, glomerular or collecting
      duct injury, respectively. An increase in urinary FABP4 levels was observed on
      days 1 and 3 after NPAA treatment and on days 14, 21, and 28 after puromycin
      treatment, whereas cisplatin treatment had no effect. No significant changes were
      reported for plasma levels of FABP4 after any treatment. Interestingly,
      immunohistochemical analysis showed a marked decrease in FABP4 expression in the
      loop of Henle on day 7 after NPAA treatment and a complete loss of FABP4
      expression on day 14 after puromycin treatment. The magnitude of increase in
      FABP4 urinary levels in response to NPAA and puromycin was higher than for
      established preclinical biomarkers serum creatinine, clusterin, or cystatin C.
      Our results suggest that FABP4 has the potential for preclinical application as a
      biomarker of DIKI.

PMID- 30215793
TI  - Spontaneous Coronary Artery Dissection in a 26-Year-Old-Male Soldier.
AB  - Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute
      coronary syndromes, which has been gaining increased recognition with the routine
      use of coronary angiography and intravascular imaging techniques in patients
      presenting with ST-elevation myocardial infarction. Here we report the case of a
      healthy, 26-year-old active-duty male presented to Tripler Army Medical Center
      for evaluation of acute onset and worsening chest pain that occurred shortly
      after participating in an Army physical fitness test. His initial EKG
      demonstrated a myocardial injury pattern with ST elevations in leads V1-V4.
      Invasive angiography revealed thrombotic occlusion of the proximal left anterior
      descending coronary artery with no evidence of atherosclerotic disease by
      intravascular ultrasound imaging. SCAD was suspected, and this diagnosis was
      confirmed after eptifibatide-induced propagation of the dissection plane
      resulting in recurrence of his index chest pain. To our knowledge, this is the
      first reported case of SCAD in the active-duty military population. SCAD is a
      rare, but important, cause of acute coronary syndromes that must be recognized by
      military providers as it necessarily precludes further military service.

PMID- 30215794
TI  - Clinical outcomes associated with anti-coagulant therapy in patients with renal
      infarction.
AB  - Background: Patients with renal infarction are vulnerable to thromboembolic
      complications with poor outcomes. There is limited report concerning the effect
      of anti-coagulant therapy in this population. Aim: To assess the impact of anti
      coagulant therapy on outcomes in patients with renal infarction. Design: A
      retrospective cohort study of 101 renal infarction patients was conducted.
      Methods: The association between anti-coagulant therapy, all-cause mortality,
      thromboembolic complications and renal outcome was evaluated. Demographic data
      and comorbidities were collected for analysis. Anti-coagulant therapy was treated
      as a time-dependent variable. Hazard ratios (HRs) and 95% confidence intervals
      (CIs) were estimated using multi-variate Cox proportional hazards models.
      Results: Fifty-seven (56.4%) patients with renal infarction received anti
      coagulant therapy during the study period. The all-cause mortality rate was 7.56
      per 100 patient-years. Age (HR 1.05, 95% CI 1.02-1.08) was a risk factor for all
      cause mortality and anti-coagulant therapy was associated with a 92% improved
      survival (HR 0.08, 95% CI 0.02-0.34). Twelve (11.9%) thromboembolic events
      occurred following renal infarction. Current smoking (HR 10.37, 95% CI 1.60
      67.43) had an adverse effect and anti-coagulant therapy (HR 0.14, 95% CI 0.03
      0.73) had a significant protective impact on thromboembolic complications. There
      was no significant association between anti-coagulant therapy and long-term renal
      outcome in renal infarction patients including the monthly change in the
      estimated glomerular filtration rate (eGFR), the incidence of eGFR reduction of
      more than 50% and end-stage renal disease. Conclusion: Anti-coagulant therapy in
      patients with renal infarction was associated with better survival and reduced
      thromboembolic complications.

PMID- 30215796
TI  - Diet Macronutrient Composition, Physical Activity, and Body Composition in
      Soldiers During 6 Months Deployment.
AB  - Introduction: Optimal diet together with good physical fitness maintains
      readiness and military performance during longer deployments. The purpose of this
      study was to describe changes in dietary macronutrient and energy intake, total
      physical activity and body composition during a 6-month deployment in South
      Lebanon. Furthermore, associations of diet macronutrient intake and physical
      activity on body composition were also studied. Materials and Methods: Forty male
      soldiers kept a 3-day food diary and their body composition was measured via
      bioimpedance and ultrasonography. Total physical activity was evaluated by
      accelerometers in a subgroup of participants. Measurements were conducted in the
      PRE-, MID-, and POST-deployment. Results: Mean carbohydrate intakes were 39.5
      42.6 E%, protein intakes 18.7-22.3 E%, and fat intakes 34.9-35.7 E%. Daily energy
      intake remained stable (10.1-10.3 MJ/D). Total physical activity was decreased
      during deployment (e.g., step count from 9,835 +/- 2,743 to 8,388 +/- 2,875
      steps/day, p = 0.007). Skeletal muscle mass and subcutaneous fat increased by
      1.3% (p = 0.019) and 1.9% (p = 0.006), respectively. Energy and fat intake
      associated positively with body mass and skeletal muscle mass (r = 0.31-0.48, p <
      0.05-0.001). Conclusions: Carbohydrate intakes and physical activity were low,
      compared with the general recommendations. Protein intakes were relatively high.
      Skeletal muscle mass and subcutaneous fat increased. Suboptimal diet together
      with low level of physical activity may have a negative impact on body
      composition, physical performance, and cardiometabolic health. Consequently,
      soldiers should be encouraged to consume more fiber-rich carbohydrates and less
      saturated fatty acids as well as maintain a high level of physical fitness to
      sustain military readiness during long-term deployments.

PMID- 30215797
TI  - Pulmonary Hydatid Disease And Serpent Sign.
AB  - A 45-year-old healthy male presented with a non-productive cough associated with
      shortness of breath for one week. Computed tomography of chest showed a cystic
      lesion in the anterior segment of left upper lobe closely abutting mediastinum
      showing air in most of the cavity with posterior dependent fluid level and an
      internal membrane-like structure, Hydatid Serology was positive. The patient was
      initially managed with Analgesics, antibiotics followed by pericystectomy.
      Hydatid cyst is a parasitic infection caused by the larval form of Echinococcus
      granulosis. On CT, a ruptured cyst shows collapsed membranes known as 'Serpent
      sign'.

PMID- 30215798
TI  - Pulmonary Arteriovenous Malformations.
AB  - A 34-year-old gentleman, presented with a recurrent headache, redness of the
      face, and shortness of breath for six months. He had congestive palpebral
      conjunctiva, reddish face and drumstick appearance of the fingers with loss of
      Lovibond angle. His SpO2 82 % at room air. Investigation showed hemoglobin 250
      g/L, hematocrit 69%, and pO2 of 44.4 mm of Hg. Erythropoietin (EPO) level was
      normal. CT pulmonary angiography images showed multiple pulmonary arteriovenous
      malformations (PAVMs) in the bilateral lower lobe of the lung. The patient
      underwent phlebotomy to relief the symptoms of hyperviscosity. PAVMs is abnormal
      communication between the pulmonary artery and pulmonary vein without capillary
      bed leading to right to left shunt physiology. It can be congenital (80% cases)
      and acquired (20%). Clinically PAVMs presents as a classical triad of dyspnea,
      cyanosis, and clubbing.

PMID- 30215795
TI  - The impact of p53 function on the metabolic activation of the carcinogenic air
      pollutant 3-nitrobenzanthrone and its metabolites 3-aminobenzanthrone and N
      hydroxy-3-aminobenzanthrone in human cells.
AB  - The tumour suppressor p53, encoded by TP53, is a key player in a wide network of
      signalling pathways. We investigated its role in the bioactivation of the
      environmental carcinogen 3-nitrobenzanthrone (3-NBA)found in diesel exhaust and
      its metabolites 3-aminobenzanthrone (3-ABA) and N-hydroxy-3-aminobenzanthrone (N
      OH-3-ABA) in a panel of isogenic human colorectal HCT116 cells differing only
      with respect to their TP53 status [i.e. TP53(+/+), TP53(+/-), TP53(-/-),
      TP53(R248W/+) or TP53(R248W/-)]. As a measure of metabolic competence, DNA adduct
      formation was determined using 32P-postlabelling. Wild-type (WT) p53 did not
      affect the bioactivation of 3-NBA; no difference in DNA adduct formation was
      observed in TP53(+/+), TP53(+/-) and TP53(-/-) cells. Bioactivation of both
      metabolites 3-ABA and N-OH-3-ABA on the other hand was WT-TP53 dependent. Lower 3
      ABA- and N-OH-3-ABA-DNA adduct levels were found in TP53(+/-) and TP53(-/-) cells
      compared to TP53(+/+) cells, and p53's impact was attributed to differences in
      cytochrome P450 (CYP) 1A1 expression for 3-ABA whereas for N-OH-3-ABA, an impact
      of this tumour suppressor on sulphotransferase (SULT) 1A1/3 expression was
      detected. Mutant R248W-p53 protein function was similar to or exceeded the
      ability of WT-p53 in activating 3-NBA and its metabolites, measured as DNA
      adducts. However, identification of the xenobiotic-metabolising enzyme(s) (XMEs),
      through which mutant-p53 regulates these responses, proved difficult to decipher.
      For example, although both mutant cell lines exhibited higher CYP1A1 induction
      after 3-NBA treatment compared to TP53(+/+) cells, 3-NBA-derived DNA adduct
      levels were only higher in TP53(R248W/-) cells but not in TP53(R248W/+) cells.
      Our results show that p53's influence on carcinogen activation depends on the
      agent studied and thereby on the XMEs that mediate the bioactivation of that
      particular compound. The phenomenon of p53 regulating CYP1A1 expression in human
      cells is consistent with other recent findings; however, this is the first study
      highlighting the impact of p53 on sulphotransferase-mediated (i.e. SULT1A1)
      carcinogen metabolism in human cells.

PMID- 30215799
TI  - RADIATION DOSE DETERMINATION IN ABDOMINAL CT EXAMINATIONS OF CHILDREN AT SUDANESE
      HOSPITALS USING SIZE-SPECIFIC DOSE ESTIMATES.
AB  - In this study, we thought to estimate the radiation exposure of children
      undergoing multi-detector CT examinations using size-specific dose estimates
      (SSDE). Console-displayed volume computed tomography dose index (CTDIvol) were
      recorded for a total of 78 paediatric abdominal CT examinations performed in six
      hospitals. Measurements of the patient diameters were taken from the mid-slice
      location on the transverse and scout CT images. Size-specific conversion
      coefficients were used to translate CTDIvol to the SSDE, according AAPM Report
      204. For children aged 0-1 y, CTDIvol, SSDEtrans (from transverse images) and
      SSDEsco (from scout images) were: 12.80 +/- 16.10, 14.43 +/- 13.22; and 14.37 +/-
      13.03 mGy; respectively. For children aged 1-5 y, CTDIvol, SSDEtrans and SSDEsco
      were: 12.11 +/- 14.47, 18.8 +/- 18.61 and 16.51 +/- 13.55 mGy; respectively. The
      obtained doses are higher than the corresponding diagnostic reference levels.
      SSDE increase with patient size as results of tube current modulation and is
      therefore a valuable tool for dose optimisation.

PMID- 30215801
TI  - A Set of Multiplex Polymerase Chain Reactions for Genomic Detection of Nine
      Edible Insect Species in Foods.
AB  - On 1 January 2018, a new regulation on 'Novel Food' has come into application in
      the EU. Insects and insect-based products are therefore included among the
      categories of food which constitute novel foods. Insects are nutrient-rich,
      produce fewer greenhouse gases and ammonia than conventional livestock, and have
      high feed conversion efficiency. Insects may be an alternative food source in the
      near future, but consideration of insects as a food requires scrutiny due to the
      risk of allergens. The aim of the present study was to develop a set of multiplex
      polymerase chain reaction (PCR) to detect nine edible insect species directly in
      foods. Four sets of mPCRs were designed to detect Locusta migratoria
      migratorioides (Reiche & Fairmaire, 1849) (Orthoptera: Acrididae), Tenebrio
      molitor (Linnaeus, 1758) (Coleoptera: Tenebrionidae) (mPCR-I), Acheta domesticus
      (Linnaeus, 1758) (Orthoptera: Gryllidae), Bombyx mori (Linnaeus, 1758)
      (Lepidoptera: Bombycidae (mPCR-II), Alphitobius diaperinus (Panzer, 1797)
      (Coleoptera: Tenebrionidae), Schistocerca gregaria (Forskal, 1775) (Orthoptera:
      Acrididae), Zophobas atratus (Fabricius, 1775) (Coleoptera: Tenebrionidae) (mPCR
      III), Galleria mellonella (Linnaeus, 1758) (Lepidoptera: Pyralidae), and
      Gryllodes sigillatus (Walker, 1869) (Orthoptera: Gryllidae) (mPCR-IV). Results
      demonstrate that the panel of mPCRs allowed a rapid genetic identification of the
      insect species and has proved to be a sensible and highly discriminatory method.
      The assay is a potential tool in issues related to the labeling of products and
      food safety, in case of allergic consumers.

PMID- 30215803
TI  - Culture and Deaf Women's Body Image.
AB  - The sociocultural model of eating disorders highlights the role of
      internalization of the thin ideal in the development of negative body image and
      disordered eating. Considering the limited diversity of models in mainstream
      media, individuals belonging to minoritized cultural groups may resist
      identifying with and internalizing mainstream beauty messages. The extent of
      internalization may also depend on an individual's acculturation status and
      experiences of acculturative stress. This study applied the sociocultural model
      to culturally Deaf women. Data were collected from 96 deaf, female, undergraduate
      students. Results support the sociocultural model; higher rates of
      internalization were associated with negative body image and disordered eating
      behaviors. However, neither Deaf nor Hearing acculturation predicted
      internalization. Despite this finding, stronger acculturation with either Deaf or
      Hearing culture predicted more positive body image, and higher rates of
      acculturative stress predicted negative body image and disordered eating
      behaviors. Implications for clinical practice are discussed.

PMID- 30215802
TI  - Genetic Variability of Melipona subnitida (Hymenoptera: Apidae) in Introduced and
      Native Populations.
AB  - Melipona subnitida (Hymenoptera: Apidae) is a stingless bee native to Caatinga
      biome in Brazil, well adapted to hot and dry climate of that region and has been
      traditionally explored for honey production. Here, we evaluate the genetic
      structure of 173 colonies of M. subnitida in northeast Brazil by partially
      sequenced mitochondrial genes cytochrome oxidase I (COI) to compare an introduced
      population isolated for 30 yr into the Island of Fernando de Noronha (IFN) with
      the continental populations. We identified high haplotype diversity (0.8220) with
      14 haplotypes on the continental populations, being three new ones, compared with
      the database GenBank. The haplotype H4 was present at the center of network,
      occurring in four localities on mainland and fixed as a single haplotype on IFN.
      We propose that the island populations originally introduced carried one
      haplotype (H4), even though IFN population is suffering pressure by island effect
      through changes on morphology. Studies on island populations could be a model to
      understand the dynamics of isolated populations and sustainable management of
      this biome to preserve M. subnitida.

PMID- 30215804
TI  - A meta-analysis of the prevalence of cardiac valvulopathy in hyperprolactinemic
      patients treated with Cabergoline.
AB  - Context: Cabergoline is first line treatment for most patients with lactotrope
      pituitary tumors and hyperprolactinemia. Its use at high-dose in Parkinson's
      disease has largely been abandoned, because of its association with the
      development of a characteristic restrictive cardiac valvulopathy. Whether similar
      valvular changes occur in patients receiving lower doses for treatment of
      hyperprolactinemia is unclear, although stringent regulatory recommendations for
      echocardiographic screening exist. Objective: To conduct a meta-analysis
      exploring any link between the use of cabergoline for the treatment of
      hyperprolactinemia and clinically-significant cardiac valvulopathy. Data Sources:
      Full-text papers published up to and including January 2017 were found via PubMed
      and selected according to strict inclusion criteria. Study selection: All case
      control studies were included where patients had received >=6 months cabergoline
      treatment for hyperprolactinemia. Single case reports, previous meta-analyses,
      review papers and papers pertaining solely to Parkinson's disease were excluded.
      13/76 originally selected studies met inclusion criteria. Data extraction: A list
      of desired data were compiled and extracted from papers by independent observers.
      Each also independently graded for paper quality (bias) and met to reach
      consensus. Data synthesis: More tricuspid regurgitation was observed (OR 3.74;
      95% CI 1.79-7.8 p<0.001) in the cabergoline treated patients compared to
      controls. In no patient was tricuspid valve dysfunction diagnosed as a result of
      clinical symptoms. There was no significant increase in any other valvulopathy.
      Conclusions: Treatment with low dose cabergoline in hyperprolactinemia appears to
      be associated with an increased prevalence of tricuspid regurgitation. The
      clinical significance of this is unclear and requires further investigation. 51.

PMID- 30215800
TI  - Assortment of Flowering Time and Immunity Alleles in Natural Arabidopsis thaliana
      Populations Suggests Immunity and Vegetative Lifespan Strategies Coevolve.
AB  - The selective impact of pathogen epidemics on host defenses can be strong but
      remains transient. By contrast, life-history shifts can durably and continuously
      modify the balance between costs and benefits of immunity, which arbitrates the
      evolution of host defenses. Their impact on the evolutionary dynamics of host
      immunity, however, has seldom been documented. Optimal investment into immunity
      is expected to decrease with shortening lifespan, because a shorter life
      decreases the probability to encounter pathogens or enemies. Here, we document
      that in natural populations of Arabidopsis thaliana, the expression levels of
      immunity genes correlate positively with flowering time, which in annual species
      is a proxy for lifespan. Using a novel genetic strategy based on bulk-segregants,
      we partitioned flowering time-dependent from -independent immunity genes and
      could demonstrate that this positive covariation can be genetically separated. It
      is therefore not explained by the pleiotropic action of some major regulatory
      genes controlling both immunity and lifespan. Moreover, we find that immunity
      genes containing variants reported to impact fitness in natural field conditions
      are among the genes whose expression covaries most strongly with flowering time.
      Taken together, these analyses reveal that natural selection has likely assorted
      alleles promoting lower expression of immunity genes with alleles that decrease
      the duration of vegetative lifespan in A. thaliana and vice versa. This is the
      first study documenting a pattern of variation consistent with the impact that
      selection on flowering time is predicted to have on diversity in host immunity.

PMID- 30215806
TI  - An Act of Man or a Caprice of Nature?

PMID- 30215805
TI  - Visceral Adipose Tissue Is Associated With Stricturing Crohn's Disease Behavior,
      Fecal Calprotectin, and Quality of Life.
AB  - Background: Visceral adipose tissue (VAT) has been proposed to play a pathogenic
      role in Crohn's disease (CD); however, prospective clinical data are lacking. The
      aim was to evaluate whether VAT, beyond body mass index (BMI), is associated with
      CD behavior, disease activity, quality of life (QoL), or outcomes. Methods: Body
      composition data and clinical, anthropometric, disease activity (fecal
      calprotectin [FC]), and QoL scores were gathered prospectively on adults with CD
      at 0, 12, and 24 months. BMI and, VAT metrics (visceral adipose tissue volume
      [cm3]/height [m2] index and VAT:subcutaneous adipose tissue [SAT] ratio) were
      calculated. Inflammatory bowel disease-related surgery and hospitalization were
      recorded over extended follow-up (median, 51 months). Multivariable linear mixed
      effects and logistic regression analyses were performed. Results: Ninety-seven
      participants were assessed at baseline (55% male; median age, 31 years), 84 at 12
      months, and 72 at 24 months. VAT:SAT was positively associated with stricturing
      disease behavior (log odds ratio [OR], 1.7; 95% confidence interval [CI], 0.32 to
      3; P = 0.01) and elevated FC in patients with ileocolonic disease (beta, 1.3; 95%
      CI, 0.32 to 2.3; P = 0.01). VAT:SAT was associated with lower QoL, particularly
      in those with ileal disease (beta, -12; 95% CI, -19 to -4.5; P = 0.05). However,
      no prospective associations were observed between serial VAT measurements and
      time to surgery or hospitalization. No correlations were found between BMI and
      disease behavior, activity, or QoL. Conclusions: VAT:SAT, rather than BMI, is
      associated with stricturing CD behavior, elevated FC, and reduced QoL in a
      disease distribution-dependent manner. Further studies are required to
      substantiate the role of VAT as a useful biomarker in CD.

PMID- 30215807
TI  - The functional anatomy of the human spermatozoon: relating ultrastructure and
      function.
AB  - The Internet, magazine articles, and even biomedical journal articles, are full
      of cartoons of spermatozoa that bear minimal resemblance to real spermatozoa,
      especially human spermatozoa, and this had led to many misconceptions about what
      spermatozoa look like and how they are constituted. This review summarizes the
      historical and current state of knowledge of mammalian sperm ultrastructure, with
      particular emphasis on and relevance to human spermatozoa, combining information
      obtained from a variety of electron microscopic (EM) techniques. Available
      information on the composition and configuration of the various ultrastructural
      components of the spermatozoon has been related to their mechanistic purpose and
      roles in the primary aspects of sperm function and fertilization: motility,
      hyperactivation, capacitation, the acrosome reaction and sperm-oocyte fusion.

PMID- 30215808
TI  - Misfolding of a DNAzyme for ultrahigh sodium selectivity over potassium.
AB  - Herein, the excellent Na+ selectivity of a few RNA-cleaving DNAzymes was
      exploited, where Na+ can be around 3000-fold more effective than K+ for promoting
      catalysis. By using a double mutant based on the Ce13d DNAzyme, and by lowering
      the temperature, increased 2-aminopurine (2AP) fluorescence was observed with
      addition of both Na+ and K+. The fluorescence increase was similar for these two
      metals at below 10 mM, after which K+ took a different pathway. Since 2AP probes
      its local base stacking environment, K+ can be considered to induce misfolding.
      Binding of both Na+ and K+ was specific, since single base mutations could fully
      inhibit 2AP fluorescence for both metals. The binding thermodynamics was measured
      by temperature-dependent experiments revealing enthalpy-driven binding for both
      metals and less coordination sites compared to G-quadruplex DNA. Cleavage
      activity assays indicated a moderate cleavage activity with 10 mM K+, while
      further increase of K+ inhibited the activity, also supporting its misfolding of
      the DNAzyme. For comparison, a G-quadruplex DNA was also studied using the same
      system, where Na+ and K+ led to the same final state with only around 8-fold
      difference in Kd. This study provides interesting insights into strategies for
      discriminating Na+ and K+.

PMID- 30215810
TI  - Prolonged warming and drought modify belowground interactions for water among
      coexisting plants.
AB  - Understanding how climate alters plant-soil water dynamics, and its impact on
      physiological functions, is critical to improved predictions of vegetation
      responses to climate change. Here we analyzed how belowground interactions for
      water shift under warming and drought, and associated impacts on plant functions.
      In a semi-arid woodland, adult trees (pinon and juniper) and perennial grasses
      (blue grama) were exposed to warming and precipitation reduction. After 6 years
      of continuous treatment exposure, soil and plant water isotopic composition was
      measured to assess plant water uptake depths and community-level water source
      partitioning. Warming and drought modified plant water uptake depths. Under
      warming, contrasting changes in water sources between grasses and trees reduced
      belowground water source partitioning, resulting in higher interspecific
      competition for water. Under drought, shifts in trees and grass water sources to
      deeper soil layers resulted in the maintenance of the naturally occurring water
      source partitioning among species. Trees showed higher water stress, and reduced
      water use and photosynthesis in response to warming and drought. This case study
      demonstrates that neighboring plants shift their competitive interactions for
      water under prolonged warming and drought, but regardless of whether changes in
      moisture sources will result in increased competition among species or maintained
      partitioning of water resources, these competitive adaptations may easily be
      overridden by climate extremes.

PMID- 30215811
TI  - Reassessing GWAS findings for the shared genetic basis of insomnia and restless
      legs syndrome.
AB  - Two genome-wide association studies (GWAS) suggest that insomnia and restless
      legs syndrome (RLS) share a common genetic basis. While the identified genetic
      variation in the MEIS1 gene was previously associated with RLS, the two GWAS
      suggest a novel and independent association with insomnia symptoms. To test the
      potential pleiotropic effect of MEIS1, we genotyped three MEIS1 variants in 646
      chronic insomnia disorder (CID) patients with and without RLS. To confirm our
      results, we compared the allelic and genotypic distributions of the CID cohort
      with ethnically matched controls and RLS cases in the French Canadian cohort. The
      CID cohort was diagnosed by sleep medicine specialists and 26% of the sample
      received the combined diagnosis of CID+RLS. We find significant differences in
      allele and genotype distributions between CID-only and CID+RLS groups, suggesting
      that MEIS1 is only associated with RLS. Genotype distributions and minor allele
      frequencies of the three MEIS1 SNPs of the CID-only and control groups were
      similar (rs113851554: 5.3% vs. 5.6%; rs2300478: 25.3% vs. 26.5%; rs12469063:
      23.6% vs. 24.4%; all p > 0.05). Likewise, there were no differences between
      CID+RLS and RLS-only groups (all p > 0.05). In conclusion, our data confirms that
      MEIS1 is a genetic risk factor for the development of RLS, but it does not
      support the pleiotropic effect of MEIS1 in CID. While a lack of power precluded
      us from refuting small pleiotropic effects, our findings emphasize the critical
      importance of isolating CID from other disorders that can cause sleep
      difficulties, particularly RLS, for future genetic studies.

PMID- 30215812
TI  - Erratum.

PMID- 30215813
TI  - Temporal dynamics of the transition period between nonrapid eye movement and
      rapid eye movement sleep in the rat.
AB  - Study Objectives: We studied the sequence of events that occur in
      electroencephalogram (EEG), electromyogram (EMG), and ocular activities along the
      transition period between nonrapid eye movement and rapid eye movement (REM)
      sleep and their temporal relationships. Methods: Twenty adult Wistar rats
      underwent polygraphic recordings of EEG, EMG, and eye movements during the
      transition periods. The studied EEG variables included the time of occurrence of
      the last sleep spindle and the evolution of the amplitudes of delta (1-5 Hz),
      theta (6-9 Hz), and high-frequency (110-160 Hz) oscillations (HFO). Motor
      variables included the development of atonia in the acromiotrapezius muscle and
      the occurrence of the first REM. The phase-amplitude coupling between theta and
      HFO was also analyzed. Results: The transition periods started with the onset of
      theta, followed by HFO onset and the decline of delta activities. From onset, HFO
      amplitude was coupled to the phase of theta. The first REM and the last sleep
      spindle coincided with the complete extinction of delta. At that point, the
      muscle tonus started to decrease, reaching its atonia when HFO achieved maximum
      amplitude. Conclusions: As the development of HFO delimited the duration of all
      transitional changes with precision, it can be considered a good delimiter for
      the transition period. Furthermore, as transitional changes occurred in a precise
      sequence, alterations in their temporal dynamics could be of interest in the
      study of sleep disorders and pathologies.

PMID- 30215809
TI  - Communication of emotion via drumming: dual-brain imaging with functional near
      infrared spectroscopy.
AB  - Nonverbal communication of emotion is essential to human interaction and relevant
      to many clinical applications, yet it is an understudied topic in social
      neuroscience. Drumming is an ancient nonverbal communication modality for
      expression of emotion that has not been previously investigated in this context.
      We investigate the neural response to live, natural communication of emotion via
      drumming using a novel dual-brain neuroimaging paradigm. Hemodynamic signals were
      acquired using whole-head functional near-infrared spectroscopy (fNIRS). Dyads of
      36 subjects participated in two conditions, drumming and talking, alternating
      between 'sending' (drumming or talking to partner) and 'receiving' (listening to
      partner) in response to emotionally salient images from the International
      Affective Picture System. Increased frequency and amplitude of drum strikes was
      behaviorally correlated with higher arousal and lower valence measures and
      neurally correlated with temporoparietal junction (TPJ) activation in the
      listener. Contrast comparisons of drumming greater than talking also revealed
      neural activity in right TPJ. Together, findings suggest that emotional content
      communicated by drumming engages right TPJ mechanisms in an emotionally and
      behaviorally sensitive fashion. Drumming may provide novel, effective clinical
      approaches for treating social-emotional psychopathology.

PMID- 30215814
TI  - Consolidation of complex motor skill learning: evidence for a delayed offline
      process.
AB  - Following initial acquisition, studies across domains have shown that memories
      stabilize through consolidation processes, requiring a post-acquisition temporal
      interval to allow their occurrence. In procedural skill memories, consolidation
      not only stabilizes the memory, but also simultaneously enhances it by
      accumulating additional gains in performance. In addition, explicit skill tasks
      were previously shown to consolidate through sleep, whereas implicit tasks were
      consolidated following a time interval which did not include a period of sleep.
      Although previous research has been instrumental in utilizing simple motor tasks
      designed to model skill learning, whether and how skill consolidation processes
      operate in complex real-life environments remains to be determined. Here, we
      tested consolidation in a complex motor skill, used to train execution of fine
      motor movements. Since the complex task was explicit, we hypothesized that
      consolidation will be evident immediately following sleep, as in simple explicit
      motor skills. However, results show that even though participants were aware of
      the goal of the complex skill task, consolidation was evident only 24 hr
      following skill acquisition, and not following a shorter 12 hr interval, even
      when the latter included sleep. An additional experiment verified that without a
      temporal interval longer than 12hr, the same skill training does not undergo
      complete consolidation. These results suggest that task complexity is a crucial
      characteristic determining the proper terms allowing full consolidation. Due to
      the enhanced ecological validity of this study, revealing the differences between
      complex and simple motor skills could enable the facilitation of advanced
      rehabilitation methods following neurological injuries.

PMID- 30215815
TI  - Professional Identity, Job Satisfaction, and Commitment of Nonphysician Faculty
      in Academic Family Medicine.
AB  - BACKGROUND AND OBJECTIVES: Nonphysician faculty are common in academic family
      medicine departments and residencies. The objective of this study was to examine
      whether these nonphysician faculty have adopted a professional identity of family
      medicine and how that relates to job satisfaction and organizational commitment.
      METHODS: In 2017, a survey of nonphysician members of the Council of Academic
      Family Medicine organizations in the United States and Canada was conducted. The
      overall response rate for the survey was 52.6% (526/1,001). The current analysis
      was conducted on the individuals who met all of the inclusion criteria and had
      complete data on all investigated scales (n=360). Scales on professional
      identity, job satisfaction, and organizational commitment were examined along
      with age, gender, race, and professional characteristics. RESULTS: The
      respondents indicated a professional identity with family medicine, commitment to
      their organization, and high job satisfaction. There was a lack of association
      with gender for these primary variables. Professional identity had a moderately
      positive relationship with years in family medicine (r=0.23). Professional
      identity had a moderately strong positive relationship with both commitment to
      the organization (r=0.41), and job satisfaction (r=0.43). In multivariate
      regressions, race/ethnicity was associated with both professional identity
      (P<.05) and job satisfaction (P<.05), with nonwhites having lower professional
      identity and job satisfaction. CONCLUSIONS: The results of this survey of
      nonphysician faculty in family medicine indicated a high professional identity to
      family medicine, high job satisfaction, and commitment to their organization.
      Strategies including cultural competency training may serve as important tools to
      avoid dissatisfaction or turnover among this key workforce element in academic
      family medicine.

PMID- 30215817
TI  - The Physician Workforce and Counting What Counts in Primary Care.

PMID- 30215816
TI  - Ethics and Family Medicine.

PMID- 30215818
TI  - Family Medicine Resident Perspectives on Curricula in Herbal Medicine.
AB  - BACKGROUND AND OBJECTIVES: Despite widespread patient use, herbal and dietary
      supplement education is not required in US-accredited medical schools. Thus,
      physicians are unprepared to address supplement use with patients. Our objectives
      were to assess perceived adequacy of medical education on supplements, determine
      resident perspectives on appropriate placement of curricula in their longitudinal
      medical education, and evaluate the effects of an innovative workshop on family
      medicine resident knowledge about supplements and intentions to address this
      topic with patients. METHODS: Family medicine residents (N=65) participated in an
      hour-long workshop covering basic concepts about herbal and dietary supplements,
      including regulations, literature review techniques, and risk/benefit analysis.
      The participants completed pre/postworkshop surveys to assess need for increased
      education and evaluate efficacy of the workshop. RESULTS: Most participants
      (91.9%) thought they should have received more education than provided on
      supplements and perceived greater need for curricula in undergraduate medical
      education than in graduate medical education. Only 47.6% received required
      education on supplements, significantly less than the 72.6% who thought this
      education should be required (P<0.05). The workshop increased the proportion of
      residents planning to address patients' supplement use, increased the frequency
      residents intend to ask about supplements, and improved resident perceptions of
      the efficacy of some supplements when used with physician guidance. CONCLUSIONS:
      Residents perceived a lack of adequate medical education on the use of herbal and
      dietary supplements. Results showed a brief workshop increased resident
      intentions to discuss supplement use with patients. Further education on
      supplement use may be warranted.

PMID- 30215819
TI  - Maintenance of Certification Part IV in Residency Methods and Impact on Practice.
AB  - BACKGROUND AND OBJECTIVES: The American Board of Family Medicine (ABFM) is the
      first medical specialty board to require all residents participate in the
      maintenance of certification (MOC) process prior to sitting for board
      certification. This study used surveys and focus groups of family medicine
      residents in four university-affiliated residency programs to explore
      participants' perceived benefits and barriers to common methods of completing the
      performance improvement in practice (Part IV) MOC requirement, and the perceived
      impact on practice. METHODS: Residents independently selected into one of three
      ABFM-approved methods of meeting the Part IV requirement. Following completion of
      the activity, participants completed a survey and then participated in a focus
      group. RESULTS: Residents cited time constraints as a major barrier to all Part
      IV methods. They also reported lack of relevance to practice, deficiencies in
      performance improvement skills, and access to clinical data. Ease of use was a
      benefit of online modules, but residents did not perceive them as relevant to
      practice or leading practice change. Portfolio and self-directed activities were
      perceived as most relevant to practice and improved patient care, and involved
      more team-based experiences. Most participants would not participate in Part IV
      if not required. CONCLUSIONS: Group quality improvement projects through the
      portfolio-approved and self-directed activities seemed to be the most positively
      reported way to complete the ABFM requirement. Regardless of method, time
      constraints and quality improvement expertise are significant barriers to
      completion of the requirement. Residency programs will need to grapple with these
      barriers to maximize benefits to residents as they prepare to become board
      certified.

PMID- 30215820
TI  - Pharmacist-Delivered Comprehensive Medication Management Within Family Medicine
      Practices An Evaluation of the SCRIPT Project.
AB  - BACKGROUND AND OBJECTIVES: Pharmacist inclusion in patient-centered medical home
      (PCMH) teams has been shown to benefit both patients and practices. However,
      pharmacists' inclusion on these teams is not widespread, partly because the work
      they do is not well known. The Successful Collaborative Relationships to Improve
      PatienT care (SCRIPT) project was started in August 2009 to understand the
      clinical and economic impact of pharmacists providing direct patient care. The
      objective of this study was to describe the work of pharmacists practicing as
      integrated members of the patient care team within PCMHs through retrospective
      analysis of their patient care documentation over a 4-year time frame. Two
      pharmacists were placed into four suburban medical home practices in Pittsburgh,
      Pennsylvania to perform comprehensive medication management (CMM). These
      pharmacists documented their CMM encounters in an electronic health record and a
      database for reporting purposes. METHODS: This study is a retrospective,
      descriptive analysis of pharmacist-documented CMM encounters from February 2010
      through February 2014. Pharmacists' work-including patient demographics, disease
      states, and medication therapy problems-was recorded in a Microsoft Access
      database and tabulated. RESULTS: The pharmacists conducted 11,206 CMM encounters
      with 3,777 unique patients during the study period. The pharmacists identified
      9,375 medication therapy problems (MTPs) and performed 14,092 interventions.
      Pharmacists most commonly worked with patients with diabetes, hypertension, pain,
      and hyperlipidemia. Physician and patient acceptance of the pharmacists' work was
      high. CONCLUSIONS: Pharmacists working in family medicine offices contribute to
      patient care through identification and resolution of MTPs and also by
      collaborating with PCMH teams.

PMID- 30215821
TI  - Difficulties in Residency: An Examination of Clinical Rotations and Competencies
      Where Family Medicine Residents Most Often Struggle.
AB  - BACKGROUND AND OBJECTIVES: Remediation in residency is expensive; however, most
      research has focused on general approaches to remediation, with minimal
      investigation into whether there are patterns to the competencies or rotations
      that are most difficult for residents. Acquiring this information may improve
      future physician training and potentially reduce the frequency of resource
      intensive remediation. We aimed to determine the competencies and rotations most
      challenging for family medicine residents, as defined by the number of
      assessments with flags (one or more competencies indicated as less than
      satisfactory). METHODS: A secondary data analysis of archived resident files from
      a large Canadian family medicine residency program was conducted. Residents from
      six cohorts were reviewed (N=393) and flags on the in-training evaluation reports
      (ITERs) and summative periodic progress reports were recorded and summarized with
      descriptive statistics. RESULTS: One hundred forty-one residents (36%) received
      at least one flag during training. Rotations where learners received the most
      flags were: internal medicine (average 1.52+/-4.82 flags), urban family medicine
      (average 1.48+/-4.18), and obstetrics (average 1.07+/-3.80). For residents having
      at least one flag, competencies causing most difficulty included: professionalism
      (21.4%), clinical decision making (17.8%), and teamwork and communication
      (15.5%). CONCLUSIONS: The file review identified coronary care unit, internal
      medicine, obstetrics, and general surgery as those rotations (adjusted for
      length) where family medicine residents most often struggled. Furthermore,
      deficient clinical knowledge was not one of the main reasons that residents are
      flagged. These findings may inform programs about where to target resident
      supports and resources.

PMID- 30215822
TI  - Trauma-Informed Care Training in Family Medicine Residency Programs Results From
      a CERA Survey.
AB  - BACKGROUND AND OBJECTIVES: Experiences of psychological trauma are common among
      primary care patient populations, and adversely affect patients' health and
      health care utilization. Trauma-informed care (TIC) is a framework for
      identifying and responding to patients' experiences of psychological trauma to
      avoid retraumatization. The purpose of this study was to evaluate the current
      state of TIC training in family medicine residency programs in the United States
      in order to identify opportunities for and barriers to TIC training. METHODS:
      Items addressing the four core domains of TIC were incorporated into the 2017
      Council of Academy Family Medicine Educational Research Alliance (CERA) survey of
      program directors. The items assessed the presence, content, and sufficiency of
      TIC curriculum, as well as barriers to further integration of TIC training.
      RESULTS: Approximately 50% of programs responded to the survey. Of 263
      respondents, 71 (27%) reported TIC training in their curriculum, but the majority
      devoted less than 5 hours annually to core content. The content most commonly
      addressed recognizing signs of trauma, most frequently using didactic formats.
      Overall, just over one-half of the programs reported that their curriculum met
      patients' TIC needs "somewhat" (48.5%) or "a great deal" (4.6%). Lack of a
      champion followed by lack of time were the most commonly cited barriers to
      integrating TIC training. CONCLUSIONS: Despite the acknowledged importance of
      effects of trauma in health care, this study identified insufficient exposure to
      training in the core TIC domains in family medicine residency programs,
      underscoring a need for greater integration of TIC training during residency.

PMID- 30215824
TI  - Two Roads.

PMID- 30215823
TI  - A Small Town Stroke.

PMID- 30215825
TI  - Luck or Destiny: How My Accidental Mentor Took Me From Impostor to Scholar.

PMID- 30215827
TI  - Your Patient Safety Survival Guide: How to Protect Yourself and Others From
      Medical Errors.

PMID- 30215826
TI  - I've Had Enough!

PMID- 30215828
TI  - An American Sickness: How Healthcare Became Big Business and How You Can Take It
      Back.

PMID- 30215829
TI  - On The Ragged Edge of Medicine: Doctoring Among the Dispossessed.

PMID- 30215830
TI  - The Use of QR Codes to Promote Timely Feedback.

PMID- 30215831
TI  - Reply to "The Use of QR Codes to Promote Timely Feedback".

PMID- 30215832
TI  - Oral Health Integration: A Call to Action.

PMID- 30215833
TI  - [Editorial].

PMID- 30215834
TI  - [Evaluation of the Association between Lithium Treatment and GSK3beta
      Polymorphism in Bipolar Disorder Patients].
AB  - OBJECTIVE: There is a lack of evidence regarding clinical predictors for the
      treatment response to lithium, which is the main stay treatment option for
      bipolar disorder. Studies that examined the mechanistic action of lithium
      revealed that glycogen synthase kinase 3beta (GSK-3beta) enzymeinhibition was
      important in regard to treatment responses. Based on this background, we aimed to
      investigate the association between responses to lithium treatment and five
      different polymorphisms of GSK-3beta. METHOD: Lithium treatment response scale
      (LTRS) scores for 100 patients diagnosed with bipolar disorders type I were
      calculated according to the hospital records. Blood samples were collected and
      genomic DNA was obtained using the MagNA Pure Compact automatic isolation method.
      The GSK-3beta: rs17183904, rs17183897, rs34009575, rs34002644, and rs17183890
      polymorphisms were analyzed by real time PCR. RESULTS: In this cohort, the mean
      age of patients was 41.1+/-10.3 years, the mean age of disease onset was 24.5+/
      8.2, and the mean LTRS score was 4.9+/-1.8. There was no statistically
      significant difference for LTRS scores between groups in terms of gender, marital
      status, level of education, and the type of first episode. LTRS was significantly
      higher in only the patients harbouring GSK-3beta rs17183890 AG genotype (p=0.008,
      t:2.71). Interestingly, no differences were found for the remaining
      polymorphisms. CONCLUSION: The specific GSK-3beta polymorphism that associated
      with lithium-response in our study may help to predict lithium responses and to
      develop individualized treatment. We presume that our pharmacogenomic findings
      may also provide important contributions to the clinical practice in regard to
      future evaluation of the treatment adherence and side effects. To obtain these
      goals, further genome-wide scanning studies conducted on larger sample cohorts
      are required.

PMID- 30215835
TI  - [Phenotypic Variants of Paraoxonase Q192R in Bipolar Disorder,Depression and
      Schizophrenia].
AB  - OBJECTIVE: Activity of the paraoxonase 1 (PON1) enzyme varies prominently
      according to the PON1 Q192R genotype. The arginine (R) genotype hydrolyzes
      peroxided lipids more quickly and efficiently than the glutamine (Q) genotype.
      The Q phenotype suggests greater liability to neurodegenerative processes,
      cardiovascular and malignancy risks than the R phenotype. Stimulated PON/ARES
      ratio is associated with the PON1 Q192R polymorphism. This study aimes to assess
      the Q192R phenotype in schizophrenia, bipolar disorder and depression. METHOD:
      Patients with schizophrenia (37), bipolar disorder (n=50), depression (n=43) and
      healthy volunteers (n=43) were enrolled. Serum PON1, stimulated paraoxonase
      (sPON) and aryl esterase (ARES) levels were assessed with an automatic analyzer.
      Clusters of sPON/ARES ratio were detected with frequency analysis in PON1. QQ, QR
      and RR variant groups. RESULTS: There were significant differences between the
      bipolar disorder, depression, schizophrenia and healthy volunteer groups in terms
      of phenotype frequencies in groups (Fisher's Exact Coefficient=18.96, p=0.003). A
      higher prevalence of the PON1 RR variant was found in bipolar disorder whereas
      the PON1 QQ variant had a higher prevalence in depression and schizophrenia as
      compared to others. Serum PON1 activity correlated with number of episodes in the
      bipolar disorder group and with SANS, SAPS scores in the schizophrenia group.
      CONCLUSION: Difference between bipolar disorder, schizophrenia and depression in
      PON1 activity and PON1 phenotype might be suggestive of different liability to
      lipid peroxidation and neurodegeneration between the diagnostic groups.
      Longitudinal studies may identify long term differences between PON1 Q192R
      polymorphisms in clinical outcomes and neuropathology.

PMID- 30215836
TI  - [The Effect of Theory of Mind Capacities of Mothers of Patients with
      Schizophrenia on the Severity of the Diseases].
AB  - OBJECTIVE: Studies conducted with patients with schizophrenia and first-degree
      relatives show that, the pathology in theory of mind may be related to the risk
      of psychosis. The theory of mind capacities of the mothers may be effective in
      the prognosis of schizophrenia. The purpose of this study is to examine the
      effects of theory of mind capacities of patient mothers on the severity of the
      disease. METHOD: The study was conducted with 34 schizophrenic patients and their
      mothers, and 31 healthy mothers. Sociodemographic data was captures for all
      groups. In addition, PANSS was collected from patients and Reading the Mind in
      the Eyes Test was collected from the each patient mother. RESULTS: There was no
      statistically significant difference between the age and education levels of the
      groups. The mothers of patients with schizophrenia performed significantly worse
      in the Reading the Mind in the Eyes Test than the control group. There was an
      inverse correlation between theory of mind capacity and the medication dose,
      PANSS general condition and PANSS total score. DISCUSSION: The significant
      difference between the groups suggests that the impairment in the function of the
      theory of mind can be regarded as an endo-phenotype for schizophrenia. The low
      theory of mind capacities of the mothers of schizophrenia patients can cause the
      mothers to misunderstand the feelings of their patient which could lead to
      increase in disease severity and drugs use.

PMID- 30215837
TI  - [Motor Proficiency in Children with Attention Deficit Hyperactivity Disorder:
      Associations with Cognitive Skills and Symptom Severity].
AB  - OBJECTIVES: Of children with Attention Deficit Hyperactivity Disorder (ADHD), 45
      70% have motor skill problems, which can adversely affect social competence, peer
      relations, and academic skills. The aim of this study is to assess motor skills
      in school-aged children with ADHD, and to elucidate if there are any
      relationships between ADHD symptoms and cognitive function. METHOD: Included in
      this study were 58 children (38 ADHD, 20 controls) between 8-11 years of age.
      Children were diagnosed with ADHD via the Schedule for Affective Disorders and
      Schizophrenia for School-Aged Children Present and Lifetime Version. The parents
      were asked to fill out the Conner's' Parent Rating Scale - Revised Short Turkish
      Form to determine the symptom domains and the symptom severity. The Wechsler
      Children's Intelligence Scale-IV was used to assess cognitive skills, and the
      Bruininks -Oseretsky Motor Proficiency Test was used to assess motor skills.
      RESULTS: Children with ADHD had impaired performance in many motor skill areas
      compared to the controls. Impairments in fine motor skills were correlated with
      problems in attention, working memory, and processing speed. In the ADHD group,
      age was not correlated with motor skills enhancement. CONCLUSION: The multistage
      clinical evaluation of ADHD should include screening for problems in motor
      skills. If deficiencies are found, the child should be clinically evaluated for
      motor proficiency and, if necessary, should be referred for appropriate objective
      assessment and intervention programs.

PMID- 30215839
TI  - [Positive Symptoms and Perceived Parental Acceptance-Rejection in Childhood: The
      Moderating Roles of Socioeconomic Status and Gender].
AB  - OBJECTIVE: The current study aimed to investigate the moderating roles of
      socioeconomic status (SES) and gender in the relationship between the positive
      symptoms of patients with schizophrenia and their recollections of parental
      acceptance-rejection in childhood. METHOD: This study included 53 outpatients (20
      females and 33 males) who were diagnosed with schizophrenia at the Ankara
      University and Ege University Faculty of Medicine Department of Psychiatry. Of
      the participants, 22.6% were from low SES families, 55.7% were from middle SES
      families, and 22.6% were from high SES families. The relationship between the
      participants' positive symptoms and recollections of parental acceptance
      rejection in childhood were assessed by the Scale for the Assessment of Positive
      Symptoms and the Adult Parental Acceptance-Rejection Questionnaire/Control.
      RESULTS: Compared to schizophrenia patients from middle and high SES families,
      those from low SES families perceived their mothers and fathers as more cold,
      neglectful, rejecting, and less controlling in their childhood. Among the
      parental acceptance-rejection subscales, only maternal indifferences/neglect was
      related to the participants' positive symptoms. A three-way interaction
      (moderated moderation) analysis indicated that SES significantly moderated the
      effect of perceived maternal neglect on positive symptoms for female, but not
      male, patients with schizophrenia. CONCLUSION: The severity of positive symptoms
      of female patients with schizophrenia, especially those from low and middle SES
      families, may be reduced by examining recollections of maternal neglect in
      childhood and, if necessary, applying trauma or attachment-focused interventions.

PMID- 30215838
TI  - [Workplace Mobbing as a Psychosocial Stress and Its Relationship to General
      Psychopathology and Psychotic Experiences Among Working Women in a University
      Hospital].
AB  - OBJECTIVE: Mobbing at work has become an alarming phenomenon worldwide. The
      prevalence of mobbing among women is higher than among men. The aim of this study
      is to investigate the relationship of mobbing as a psychosocial stress in the
      workplace with general psychopathology and psychotic experiences among women.
      METHOD: 428 women from the Medical Faculty of Dokuz Eylul University were
      included in the study. Of the 428 women, 139 were doctors, 190 were nurses, and
      99 were sub-contracted employees. Stratified and cluster sampling METHODS were
      used. Sociodemographic data form, mobbing scale and symptom checklist (SCL-90-R)
      were used in order to collect the data. RESULTS: 304 (71%) of the participants
      had experienced mobbing at least once. It was determined that nurses had
      experienced mobbing more frequently than doctors and sub-contracted employee.
      Total and subscale scores of the mobbing scale were statistically higher in
      participants who went to psychiatry outpatient clinics and who use psychiatric
      medication and alcohol. There was a positive statistically significant
      correlation between SCL-90-R and mobbing scale scores. Correlation coefficients
      ranged from 0.25 to 0.56. The highest correlation was between the paranoid sub
      scale of SCL-90-R and mobbing (r= 0.56) CONCLUSION: Generally, exposure to
      mobbing seems to be related with higher psychopathology. Also, according to our
      research results, mobbing is a psychosocial stress source that might be
      triggering subthreshold psychotic experiences.

PMID- 30215840
TI  - [Reliability and Validity Study of the Turkish Version of Bipolar Prodrome
      Symptom Scale].
AB  - OBJECTIVE: In this study, it is aimed to evaluate the reliability and validity of
      the Turkish version of Bipolar Prodrome Symptom Scale. METHOD: The study was
      carried out with subjects who participated the study on the epidemiology of
      bipolar disorder among the students in the 1st grade of Celal Bayar University.
      The sample consisted of 30 volunteers diagnosed as bipolar disorder and 122
      healthy controls. For concurrent validity, Hypomania Checklist-32-Revised 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 were performed and thus the semantic harmony
      of the scale was obtained. In the internal consistency, Cronbach alpha
      coefficient was between 0,969-0,979 and item-total score correlations were
      between 0,767-0,929 and 0,725-0,890. In factor analysis, for the severity
      subscale a one-factor solution representing 78,9% of the variance and for the
      frequency subscale one-factor solution representing 71,7% of the solution are
      obtained. Correlation of Bipolar Prodrome Symptom Scale with Hypomania Checklist
      32-Revised was r=0,513 and 0,530. In the ROC analysis, area under the curve was
      0,977 and 0,999. The scale discriminates well between the bipolar group and
      healthy control group. CONCLUSION: Bipolar Prodrome Symptom Scale developed for
      screening hypomania is reported to be reliable and valid in Turkish.

PMID- 30215841
TI  - [Dimensional Approach to Obsessive-Compulsive Disorder: Dimensional Obsessive
      Compulsive Scale with Turkish Psychometric Properties].
AB  - OBJECTIVE: The Dimensional Obsessive Compulsive Scale (DOCS) is a measurement
      tool that examines the severity of thematically distinct symptom domains of
      obsessive compulsive disorder (OCD). In this study we assess psychometric
      properties of the Turkish version of DOCS. METHODS: Ninety-six patients who
      presented consecutively to the Diskapi Yildirim Beyazit Teaching and Research
      Hospital outpatient unit and who were diagnosed with OCD according to the DSM-IV
      TR criteria were enrolled in the study. The DOCS, Yale-Brown Obsessive Compulsive
      Scale (YBOCS), and Padua Inventory (PI) were completed by the participants.
      Internal consistency was estimated using Cronbach?s Alpha values and item-total
      correlations. Principal component analyses with Varimax rotation were used to
      assess latent factor structure . RESULTS: Explanatory Factor Analyses (EFA)
      revealed a 4-factor solution for the DOCS. Chronbach?s alpha values for the whole
      scale, ?contamination? sub-scale, ?responsibility? sub-scale, ?unacceptable
      thoughts?, and ?symmetry? sub-scales were 0.874, 0.932, 0.933, 0.948, 0.921,
      respectively. There was a high correlation between both total scores and sub
      scales scores of DOCS, YBOCS and PI. CONCLUSIONS: Internal consistencies were
      good for the total scale and excellent for the sub-scales. The factor structure
      and the contents of the factors were perfectly in line with the original scale
      (i.e. 4 factor). Positive correlations between DOCS, its sub-scales, and similar
      OCD scales suggest that the DOCS accurately measures the structures it claims to
      assess. Thus the DOCS Turkish version can measure dimensional obsessive
      compulsive symptoms among the Turkish speaking OCD population.

PMID- 30215842
TI  - [The Function of the Expression "I am Unlucky" with Respect to Masochistic
      Personality].
AB  - In this paper, complaints of "unluckiness," which are often heard in
      psychotherapy, are discussed with respect to masochistic personality. Luck is a
      concept that belongs to the outer world. However, the phrase "I am unlucky" can
      be a concept that becomes a part of one's own identity. Some clients in the
      therapy process, either explicitly or implicitly, express the idea that they are
      unluckier than other people. Seeing one's self as unluckier than others poses
      problems in the therapy process. The 'unluckiness' becomes a personality trait
      that is extremely difficult to handle, and thus, the therapist's job becomes just
      as difficult. Moreover, while luck is an outer world concept, unluckiness becomes
      a part of one's identity, and the boundary between the inner and outer worlds
      vanishes. In this paper, it is described how two clients in psychoanalytical
      oriented therapy defined themselves as unlucky. The material from these cases is
      discussed using psychoanalytic concepts. An overly punitive superego, the need
      for punishment, death drive, and masochistic personality are the major axes of
      the discussion. It has been argued that in many instances where one describes
      him/herself as being unlucky, there may be an aggressive act in which the person
      aims harm at him/herself. The dynamics of this aggressive act are discussed. One
      of the major aspects of masochistic personality, the fantasy of "If I torture
      myself enough, eventually I will be loved" is also discussed. The view that the
      need for self-punishment or unconscious feelings of guilt may be obscuring
      feelings of grief is elaborated within the context of Winnicott's transition
      object concept. It has been argued that if the phrase "I am unlucky," which poses
      problems for therapists, is better understood, it may be better handled in the
      therapy process.

PMID- 30215843
TI  - [Eye Movement Desensitization and Reprocessing (EMDR) Therapy on a Patient with
      Schizophrenia and Clinical Effects: A Case Study].
AB  - Being exposed to traumatic experiences is rather common in patients with
      schizophrenia. Adverse experiences may induce the onset of psychotic symptoms or
      trigger current symptoms to be exacerbated. Eye Movement Desensitization
      Reprocessing (EMDR) is an effective therapy in the treatment of incidences with
      underlying traumatic experiences, there by it can be conducted on various cases
      in addition to other treatments such as psycho-medication or another therapy
      method. It was developed by Shapiro in 1980s. Although desensitization is widely
      applied on patients with Post-Traumatic Stress Disorder, it is unusual for EMDR
      therapy to be safely and effectively performed in the treatment of psychotic
      disorder sor symptoms. In the present case study, EMDR treatment process and
      course of psychiatric state in a patient with history of child hood abuse and
      forced psychiatric residency will be discussed. The patient who had a diagnosis
      of schizophrenia for 8 years was treated with antipsychotic treatment as well as
      2 sessions of EMDR, and as a result, a positive change was observed in her
      general clinical course. Our thoughts on this phenomenon are that EMDR treatment
      is an effective, safe and short-term intervention in the comorbidity of PTSD and
      psychotic disorders. However, the literature about the place of EMDR in the
      treatment of schizophrenia cases is rather limited and much more research is
      needed.

PMID- 30215844
TI  - [Pagophagia in a Female with Recurrent Depressive Disorder:A Case Report with
      Review of Literature].
AB  - "Pica" is the term used to describe craving for non-food and nonnutritive items
      like dirt, chalk, or paper. Pagophagia (compulsive ice chewing) is a particular
      form of pica that is characterized by ingestion of ice, freezer frost, or iced
      drinks. It is usually associated with iron deficiency anemia or mental
      abnormalities like intellectual disabilities, autism, etc. Very few case reports
      have reported association of eating ice cubes with compulsive behavior or
      depressive disorders. In this case report, we present the association of
      pagophagia with sadness in a patient with recurrent depressive disorder. A 44
      year-old female suffering from depressive disorder since the age of 33 years
      presented with symptoms of an intense desire to eat ice cubes that she was unable
      to resist and would feel better only after consumption of ice cubes or iced
      drinks. Initially she would consume about 250-500 g of ice cubes per day, but
      gradually the quantity of consumption of ice increased to about 10-12 kg of ice
      cubes per day. These symptoms were related to low mood and stress. The
      preoccupation with consumption of ice was associated with significant
      psychosocial dysfunction and interpersona problems with the spouse. She was
      managed with venlafaxine 187.5 mg/day and cognitive behavior psychotherapy
      (identifying her cognitive errors, generating alternative thoughts, problem
      solving, activity scheduling and mastery, and pleasure technique) with which her
      depressive symptoms improved and her pagophagia reduced significantly but did not
      subside completely. She learned to use alternative coping mechanisms to deal with
      her psychosocial stressors.

PMID- 30215845
TI  - Polymorphisms in P53 and VEGFA genes in different subtypes of periorbital
      hyperpigmentation in a Malaysian Chinese population.
AB  - BACKGROUND/OBJECTIVES: The unknown pathogenesis of periorbital hyperpigmentation
      makes its treatment difficult. Existing evidence links p53 and VEGFA genes with
      skin hyperpigmentation. This study was aimed at (i) identifying the clinical
      pattern of periorbital hyperpigmentation; and (ii) detecting the presence of
      VEGFA and P53 single nucleotide polymorphism (SNPs) in different subtypes of
      periorbital hyperpigmentation in Malaysian Chinese. METHODS: A cross-sectional
      study was conducted among Malaysian Chinese. Clinical assessments were performed,
      and medical history was collected. Three regions of p53 and two of VEGFA were
      amplified by PCR followed by direct sequencing using saliva-extracted DNA.
      RESULTS: Eighty-four participants were recruited (average age 22.2 years). In the
      majority (n = 62), both eyelids were affected. Facial pigmentary, demarcation
      lines, tear trough and eye bags were not observed. Mixed (pigmented-vascular) was
      the most common subtype. Thirteen SNPs were found, nine of which are new. Only
      three out of 13 SNPs showed significant association with periorbital
      hyperpigmentation presentation. TA genotype in rs1437756379 (p53) was
      significantly more prevalent among participants with mixed subtype (P = 0.011)
      while AC genotype in rs1377053612 (VEGFA) was significantly more prevalent among
      pigmented subtype (P = 0.028). AA genotype in rs1479430148 (VEGFA) was
      significantly associated with allergic rhinitis in mixed subtype (P = 0.012).
      CONCLUSION: Mixed subtype was the most prevalent type of periorbital
      hyperpigmentation in the study population. Three polymorphisms in p53 and VEGFA
      genes were statistically linked with different clinical presentations of
      periorbital hyperpigmentation.

PMID- 30215846
TI  - Ensuring quality as the basis of evidence synthesis: leveraging information
      specialists' knowledge, skills, and expertise.

PMID- 30215847
TI  - Art therapy for people with dementia.
AB  - BACKGROUND: Art therapy is defined by the British Association of Art Therapists
      as: "a form of psychotherapy that uses art media as its primary mode of
      communication. Clients who are referred to an art therapist need not have
      experience or skill in art. The art therapist is not primarily concerned with
      making an aesthetic or diagnostic assessment of the client's image. The overall
      aim of its practitioners is to enable a client to change and grow on a personal
      level through the use of art materials in a safe and facilitating environment".
      Historically, drawings and paintings have been recognised as a useful part of
      therapeutic processes within psychiatric and psychological specialties, and this
      has been acknowledged within medical and neurology-based disciplines.Arts-based
      therapies are generally considered as interventions managing manifestations of
      dementia, as they may help to slow cognitive deterioration, address symptoms
      related to psychosocially challenging behaviours and improve quality of life.
      OBJECTIVES: To review the effects of art therapy as an adjunctive treatment for
      dementia compared with standard care and other non-pharmacological interventions.
      SEARCH METHODS: We identified trials from ALOIS - the Cochrane Dementia and
      Cognitive Improvement Group's Specialised Register - on 12 May 2014, 20 March
      2015, 15 January 2016, 4 November 2016, and 4 October 2017. We also handsearched
      the grey literature and contacted specialists in the field and authors of
      relevant reviews or studies to enquire about other sources of relevant
      information. SELECTION CRITERIA: All randomised controlled trials examining art
      therapy as an intervention for dementia. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data. We examined scales measuring cognition,
      affect and emotional well-being, social functioning, behaviour and quality of
      life. MAIN RESULTS: We found two studies that met the inclusion criteria,
      incorporating data on a total of 60 participants (from 88 randomised), in
      experimental groups (n = 29) and active control groups (n = 31). One study
      compared group art therapy with simple calculation activities over 12 weeks. The
      other study compared group art therapy with recreational activities over 40
      weeks. It was not possible to pool the data for analysis from the included
      studies, due to heterogeneity in terms of differences in the interventions,
      control treatments and choice of outcome measures.In both studies there were no
      clear changes reported between the intervention group and the control group in
      the important outcome measures. According to GRADE ratings, we judged the quality
      of evidence for these outcome measures to be 'very low'. AUTHORS' CONCLUSIONS:
      There is insufficient evidence about the efficacy of art therapy for people with
      dementia. More adequately-powered and high-quality studies using relevant outcome
      measures are needed.

PMID- 30215848
TI  - Hepatobiliary and Pancreatic: Inflammatory myofibroblastic tumor of the liver
      mimicking intrahepatic cholangiocarcinoma with hilar lymph node metastasis.

PMID- 30215849
TI  - A challenging case: Multiple and Blaschkoid hair follicle naevi or supernumerary
      accessory tragi?

PMID- 30215851
TI  - Age-dependent effect of targeted temperature management on outcome after cardiac
      arrest.
AB  - BACKGROUND: In elder patients after out-of-hospital cardiac arrest, diminished
      neurologic function as well as reduced neuronal plasticity may cause a low
      response to targeted temperature management (TTM). Therefore, we investigated the
      association between TTM (32-34 degrees C) and neurologic outcome in cardiac
      arrest survivors with respect to age. MATERIAL AND METHODS: This retrospective
      cohort study included patients 18 years of age or older suffering a witnessed out
      of-hospital cardiac arrest with presumed cardiac cause, which remained comatose
      after return of spontaneous circulation. Patients were a priori split by age into
      four groups (<50 years (n = 496); 50-64 years (n = 714); 65-74 years (n = 395);
      >75 years (n = 280)). Subsequently, within these groups, patients receiving TTM
      were compared to those not treated with TTM. RESULTS: Out of 1885 patients, 921
      received TTM for 24 hours. TTM was significantly associated with good neurologic
      outcome in patients <65 years of age whereas showing no effect in elders (65-74
      years: OR: 1.49 (95% CI: 0.90-2.47); > 75 years: OR 1.44 (95% CI 0.79-2.34)).
      CONCLUSION: In our cohort, it seems that TTM might not be able to achieve the
      same benefit for neurologic outcome in all age groups. Although the results of
      this study should be interpreted with caution, TTM was associated with improved
      neurologic outcome only in younger individuals, patients with 65 years of age or
      older did not benefit from this treatment.

PMID- 30215850
TI  - Hepatocyte-specific beta-catenin deletion during severe liver injury provokes
      cholangiocytes to differentiate into hepatocytes.
AB  - : Liver regeneration after injury is normally mediated by proliferation of
      hepatocytes, although recent studies have suggested biliary epithelial cells
      (BECs) can differentiate into hepatocytes during severe liver injury when
      hepatocyte proliferation is impaired. We investigated the effect of hepatocyte
      specific beta-catenin deletion in recovery from severe liver injury and BEC-to
      hepatocyte differentiation. To induce liver injury, we administered choline
      deficient, ethionine-supplemented (CDE) diet to three different mouse models, the
      first being mice with deletion of beta-catenin in both BECs and hepatocytes
      (Albumin-Cre; Ctnnb1flox/flox mice). In our second model, we performed hepatocyte
      lineage tracing by injecting Ctnnb1flox/flox ; Rosa-stopflox/flox -EYFP mice with
      the adeno-associated virus serotype 8 encoding Cre recombinase under the control
      of the thyroid binding globulin promoter (AAV8-TBG-Cre), a virus which infects
      only hepatocytes. Finally, we performed BEC lineage tracing via Krt19-CreERT ;
      Rosa-stopflox/flox -tdTomato mice. To observe BEC-to-hepatocyte differentiation,
      mice were allowed to recover on normal diet following CDE diet-induced liver
      injury. Livers were collected from all mice and analyzed by quantitative real
      time polymerase chain reaction, western blotting, immunohistochemistry, and
      immunofluorescence. We show that mice with lack of beta-catenin in hepatocytes
      placed on the CDE diet develop severe liver injury with impaired hepatocyte
      proliferation, creating a stimulus for BECs to differentiate into hepatocytes. In
      particular, we use both hepatocyte and BEC lineage tracing to show that BECs
      differentiate into hepatocytes, which go on to repopulate the liver during long
      term recovery. CONCLUSION: beta-catenin is important for liver regeneration after
      CDE diet-induced liver injury, and BEC-derived hepatocytes can permanently
      incorporate into the liver parenchyma to mediate liver regeneration. This article
      is protected by copyright. All rights reserved.

PMID- 30215852
TI  - Genetic screening for macular dystrophies in patients clinically diagnosed with
      dry age-related macular degeneration.
AB  - It can be clinically challenging to distinguish dry age-related macular
      degeneration (AMD) from AMD-mimicking dystrophies, and sometimes misdiagnosis
      occurs. With upcoming therapies for dry AMD it is important to exclude patients
      with a different retinal disease from clinical trials. In this study we evaluated
      the occurrence of AMD-mimicking dystrophies in an AMD cohort. Whole-exome
      sequencing (WES) was performed in 218 patients with intermediate AMD or
      geographic atrophy secondary to AMD and 133 control individuals. WES data was
      analyzed for rare variants in 19 genes associated with autosomal dominant and
      recessive macular dystrophies mimicking AMD. In three (1.4%) of 218 cases we
      identified a pathogenic heterozygous variant (PRPH2 c.424C > T; p.R142W) causal
      for autosomal dominant central areolar choroidal dystrophy (CACD).
      Phenotypically, these patients all presented with geographic atrophy. In 12
      (5.5%) of 218 cases we identified a heterozygous variant of unknown clinical
      significance, but predicted to be highly deleterious, in genes previously
      associated with autosomal dominant macular dystrophies. The distinction between
      AMD and AMD-mimicking dystrophies, such as CACD, can be challenging based on
      fundus examination alone. Genetic screening for genes associated with macular
      dystrophies, especially PRPH2, can be beneficial to help identify AMD-mimicking
      dystrophies.

PMID- 30215854
TI  - The interstitial space takes shape.
AB  - In March 2018, Benias et al. published a study, entitled "Structure and
      distribution of an unrecognized interstitium in human tissues"(1), which received
      extensive news coverage. The authors utilized a variety of methods, including in
      vivo and ex vivo confocal laser endomicroscopy, frozen and routine histologic
      preparations, immunohistochemistry, electron microscopy and second harmonic
      generation microscopy, to provide novel information on the structure and function
      of the interstitial space. This article is protected by copyright. All rights
      reserved.

PMID- 30215853
TI  - Cardiac surgery for Chagas disease.
AB  - Although Chagas disease is a rare entity in North America, it is associated with
      significant cardiac morbidity. It is estimated that 20-30% of those who are
      infected will eventually develop cardiovascular disease secondary to Chagas
      disease. We review the literature and share our experience on the surgical
      management of this challenging patient population.

PMID- 30215855
TI  - Ultra-performance liquid chromatography tandem mass spectrometry for the rapid,
      simultaneous analysis of ziprasidone and its impurities.
AB  - The separation and characterization of the unknown degradation product of second
      generation antipsychotic drug ziprasidone are essential for defining the
      genotoxic potential of the compound. The aim of this study was to develop a
      simple UHPLC method coupled with tandem mass spectrometry (MS/MS) for chemical
      characterization of an unknown degradant, and the separation and quantification
      of ziprasidone and its five main impurities (I-V) in the raw material and
      pharmaceuticals. Chromatographic conditions were optimized by experimental
      design. The MS/MS fragmentation conditions were optimized individually for each
      compound in order to obtain both specific fragments and high signal intensity. A
      rapid and sensitive UHPLC-MS/MS method was developed. All seven analytes were
      eluted within the 7 min run time. The best separation was obtained on the Acquity
      UPLC BEH C18 (50 * 2.1 mm * 1.7 MUm) column in gradient mode with ammonium
      formate buffer (10 mm; pH 4.7) and acetonitrile as mobile phase, with the flow
      rate of 0.3 mL min-1 and at the column temperature of 30 degrees C. The new UHPLC
      MS/MS method was fully validated and all validation parameters were confirmed.
      The fragmentation pathways and chemical characterization of an unknown degradant
      were proposed and it was confirmed that there are no structural alerts concerning
      genotoxicity.

PMID- 30215856
TI  - Immunomodulators targeting the PD-1/PD-L1 protein-protein interaction: From
      antibodies to small molecules.
AB  - Cancer immunotherapy has made great strides in the recent decade, especially in
      the area of immune checkpoint blockade. The outstanding efficacy, prolonged
      durability of effect, and rapid assimilation of anti-PD-1 and anti-PD-L1
      monoclonal antibodies in clinical practice have been nothing short of a medical
      breakthrough in the treatment of numerous malignancies. The major advantages of
      these therapeutic antibodies over their small molecule counterparts have been
      their high binding affinity and target specificity. However, antibodies do have
      their flaws including immune-related toxicities, inadequate pharmacokinetics and
      tumor penetration, and high cost burden to manufacturers and consumers. These
      limitations hinder broader clinical applications of the antibodies and have
      heightened interests in developing the alternative small molecule platform that
      includes peptidomimetics and peptides to target the PD-1/PD-L1 immune checkpoint
      system. The progress on these small molecule alternatives has been relatively
      slow compared to that of the antibodies. Fortunately, recent structural studies
      of the interactions among PD-1, PD-L1, and their respective antibodies have
      revealed key hotspots on PD-1 and PD-L1 that may facilitate drug discovery
      efforts for small molecule immunotherapeutics. This review is intended to discuss
      key concepts in immuno-oncology, describe the successes and shortcomings of PD
      1/PD-L1 antibody-based therapies, and to highlight the recent development of
      small molecule inhibitors of the PD-1/PD-L1 protein-protein interaction.

PMID- 30215857
TI  - Immunobiology of Inherited Muscular Dystrophies.
AB  - The immune response to acute muscle damage is important for normal repair.
      However, in chronic diseases such as many muscular dystrophies, the immune
      response can amplify pathology and play a major role in determining disease
      severity. Muscular dystrophies are inheritable diseases that vary tremendously in
      severity, but share the progressive loss of muscle mass and function that can be
      debilitating and lethal. Mutations in diverse genes cause muscular dystrophy,
      including genes that encode proteins that maintain membrane strength, participate
      in membrane repair, or are components of the extracellular matrix or the nuclear
      envelope. In this article, we explore the hypothesis that an important feature of
      many muscular dystrophies is an immune response adapted to acute, infrequent
      muscle damage that is misapplied in the context of chronic injury. We discuss the
      involvement of the immune system in the most common muscular dystrophy, Duchenne
      muscular dystrophy, and show that the immune system influences muscle death and
      fibrosis as disease progresses. We then present information on immune cell
      function in other muscular dystrophies and show that for many muscular
      dystrophies, release of cytosolic proteins into the extracellular space may
      provide an initial signal, leading to an immune response that is typically
      dominated by macrophages, neutrophils, helper T-lymphocytes, and cytotoxic T
      lymphocytes. Although those features are similar in many muscular dystrophies,
      each muscular dystrophy shows distinguishing features in the magnitude and type
      of inflammatory response. These differences indicate that there are disease
      specific immunomodulatory molecules that determine response to muscle cell damage
      caused by diverse genetic mutations. (c) 2018 American Physiological Society.
      Compr Physiol 8:1313-1356, 2018.

PMID- 30215858
TI  - ATP-Sensitive Potassium Channels and Their Physiological and Pathophysiological
      Roles.
AB  - ATP sensitive potassium channels (KATP ) are so named because they open as
      cellular ATP levels fall. This leads to membrane hyperpolarization and thus links
      cellular metabolism to membrane excitability. They also respond to MgADP and are
      regulated by a number of cell signaling pathways. They have a rich and diverse
      pharmacology with a number of agents acting as specific inhibitors and
      activators. KATP channels are formed of pore-forming subunits, Kir6.1 and Kir6.2,
      and a large auxiliary subunit, the sulfonylurea receptor (SUR1, SUR2A, and
      SUR2B). The Kir6.0 subunits are a member of the inwardly rectifying family of
      potassium channels and the sulfonylurea receptor is part of the ATP-binding
      cassette family of proteins. Four SURs and four Kir6.x form an octameric channel
      complex and the association of a particular SUR with a specific Kir6.x subunit
      constitutes the KATP current in a particular tissue. A combination of mutagenesis
      work combined with structural studies has identified how these channels work as
      molecular machines. They have a variety of physiological roles including
      controlling the release of insulin from pancreatic beta cells and regulating
      blood vessel tone and blood pressure. Furthermore, mutations in the genes
      underlie human diseases such as congenital diabetes and hyperinsulinism.
      Additionally, opening of these channels is protective in a number of pathological
      conditions such as myocardial ischemia and stroke. (c) 2018 American
      Physiological Society. Compr Physiol 8:1463-1511, 2018.

PMID- 30215859
TI  - Colonic Potassium Absorption and Secretion in Health and Disease.
AB  - The colon has large capacities for K+ absorption and K+ secretion, but its role
      in maintaining K+ homeostasis is often overlooked. For many years, passive
      diffusion and/or solvent drag were thought to be the primary mechanisms for K+
      absorption in human and animal colon. However, it is now clear that apical H+ ,K+
      -ATPase, in coordination with basolateral K+ -Cl- cotransport and/or K+ and Cl-
      channels operating in parallel, mediate electroneutral K+ absorption in animal
      colon. We now know that K+ absorption in rat colon reflects ouabain-sensitive and
      ouabain-insensitive apical H+ ,K+ -ATPase activities. Ouabain-insensitive and
      ouabain-sensitive H+ ,K+ -ATPases are localized in surface and crypt cells,
      respectively. Colonic H+ ,K+ -ATPase consists of alpha- (HKCalpha ) and beta-
      (HKCbeta ) subunits which, when coexpressed, exhibit ouabain-insensitive H+ ,K+ 
      ATPase activity in HEK293 cells, while HKCalpha coexpressed with the gastric beta
      subunit exhibits ouabain-sensitive H+ ,K+ -ATPase activity in Xenopus oocytes.
      Aldosterone enhances apical H+ ,K+ -ATPase activity, HKCalpha specific mRNA and
      protein expression, and K+ absorption. Active K+ secretion, on the other hand, is
      mediated by apical K+ channels operating in a coordinated way with the
      basolateral Na+ -K+ -2Cl- cotransporter. Both Ca2+ -activated intermediate
      conductance K+ (IK) and large conductance K+ (BK) channels are located in the
      apical membrane of colonic epithelia. IK channel-mediated K+ efflux provides the
      driving force for Cl- secretion, while BK channels mediate active (e.g., cAMP
      activated) K+ secretion. BK channel expression and activity are increased in
      patients with end-stage renal disease and ulcerative colitis. This review
      summarizes the role of apical H+ ,K+ -ATPase in K+ absorption, and apical BK
      channel function in K+ secretion in health and disease. (c) 2018 American
      Physiological Society. Compr Physiol 8:1513-1536, 2018.

PMID- 30215860
TI  - Androgens and the Regulation of Adiposity and Body Fat Distribution in Humans.
AB  - The sexual dimorphism in human body fat distribution suggests a causal role for
      sex hormones. This is of particular importance when considering the role of
      excess visceral adipose tissue accumulation as a critical determinant of obesity
      related cardiometabolic alterations. Scientific literature on the modulation of
      body fat distribution by androgens in humans is abundant, remarkably inconsistent
      and difficult to summarize. We reviewed relevant literature on this topic, with a
      particular emphasis on androgen replacement, androgen effects on selected
      parameters of adipose tissue function and adipose tissue steroid-converting
      enzymes. In men, low androgenic status mostly reflected by reduced total
      testosterone is a frequent feature of visceral obesity and the metabolic
      syndrome. Regarding testosterone therapy, however, studies must be appreciated in
      the context of current controversies on their cardiovascular effects. Analyses of
      available studies suggest that decreases in waist circumference in response to
      testosterone are more likely observed in men with low levels of testosterone and
      high BMI at study onset. In women with androgen excess, higher testosterone and
      free testosterone levels are fairly consistent predictors of increased abdominal
      and/or visceral adipose tissue accumulation, which is not the case in
      nonhyperandrogenic women. Regarding mechanisms, androgens decrease adipogenesis
      and markers of lipid storage in vitro in men and women. Evidence also suggest
      that local steroid transformations by adipose tissue steroid-converting enzymes
      expressed in a depot-specific fashion may play a role in androgen-mediated
      modulation of body fat distribution. Accumulating evidence shows that androgens
      are critical modulators of body fat distribution in both men and women. (c) 2018
      American Physiological Society. Compr Physiol 8:1253-1290, 2018.

PMID- 30215861
TI  - Systemic Oxygen Transport with Rest, Exercise, and Hypoxia: A Comparison of
      Humans, Rats, and Mice.
AB  - The objective of this article is to compare and contrast the known
      characteristics of the systemic O2 transport of humans, rats, and mice at rest
      and during exercise in normoxia and hypoxia. This analysis should help understand
      when rodent O2 transport findings can-and cannot-be applied to human responses to
      similar conditions. The O2 -transport system was analyzed as composed of four
      linked conductances: ventilation, alveolo-capillary diffusion, circulatory
      convection, and tissue capillary-cell diffusion. While the mechanisms of O2
      transport are similar in the three species, the quantitative differences are
      naturally large. There are abundant data on total O2 consumption and on
      ventilatory and pulmonary diffusive conductances under resting conditions in the
      three species; however, there is much less available information on pulmonary gas
      exchange, circulatory O2 convection, and tissue O2 diffusion in mice. The
      scarcity of data largely derives from the difficulty of obtaining blood samples
      in these small animals and highlights the need for additional research in this
      area. In spite of the large quantitative differences in absolute and mass
      specific O2 flux, available evidence indicates that resting alveolar and arterial
      and venous blood PO2 values under normoxia are similar in the three species.
      Additionally, at least in rats, alveolar and arterial blood PO2 under hypoxia and
      exercise remain closer to the resting values than those observed in humans. This
      is achieved by a greater ventilatory response, coupled with a closer value of
      arterial to alveolar PO2 , suggesting a greater efficacy of gas exchange in the
      rats. (c) 2018 American Physiological Society. Compr Physiol 8:1537-1573, 2018.

PMID- 30215862
TI  - Distribution and Stimulus Secretion Coupling of Enteroendocrine Cells along the
      Intestinal Tract.
AB  - The enteroendocrine system of the gut acts both locally and peripherally,
      regulating gastrointestinal function as well as metabolism, energy expenditure,
      and central appetite control through the release of a variety of hormones. The
      chemosensing ability of enteroendocrine cells is integral to their role in
      eliciting physiological changes in response to fluctuations in the composition of
      the intestinal lumen. Regulation of enteroendocrine cell activity is complex, and
      requires that these cells can integrate signals deriving from dietary sources as
      well as the nervous and endocrine systems. Here, we provide an overview of
      enteroendocrine cell form and function, with a focus on new insights into their
      distribution throughout the intestine and the stimulus secretion coupling
      mechanisms underlying the activity of these important members of the gut-brain
      axis. (c) 2018 American Physiological Society. Compr Physiol 8:1603-1638, 2018.

PMID- 30215863
TI  - Adipose Organ Development and Remodeling.
AB  - During the last decades, research on adipose tissues has spread in parallel with
      the extension of obesity. Several observations converged on the idea that adipose
      tissues are organized in a large organ with endocrine and plastic properties. Two
      parenchymal components: white (WATs) and brown adipose tissues (BATs) are
      contained in subcutaneous and visceral compartments. Although both have endocrine
      properties, their function differs: WAT store lipids to allow intervals between
      meals, BAT burns lipids for thermogenesis. In spite of these opposite functions,
      they share the ability for reciprocal reversible transdifferentiation to tackle
      special physiologic needs. Thus, chronic need for thermogenesis induces browning
      and chronic positive energy balance induce whitening. Lineage tracing and data
      from explant studies strongly suggest other remodeling properties of this organ.
      During pregnancy and lactation breast WAT transdifferentiates into milk-secreting
      glands, composed by cells with abundant cytoplasmic lipids (pink adipocytes) and
      in the postlactation period pink adipocytes transdifferentiate back into WAT and
      BAT. The plastic properties of mature adipocytes are supported also by a
      liposecretion process in vitro where adult cell in culture transdifferentiate to
      differentiated fibroblast-like elements able to give rise to different phenotypes
      (rainbow adipocytes). In addition, the inflammasome system is activated in
      stressed adipocytes from obese adipose tissue. These adipocytes die and debris
      are reabsorbed by macrophages inducing a chronic low-grade inflammation,
      potentially contributing to insulin resistance and T2 diabetes. Thus, the plastic
      properties of this organ could open new therapeutic perspectives in the obesity
      related metabolic disease and in breast pathologies. (c) 2018 American
      Physiological Society. Compr Physiol 8:1357-1431, 2018.

PMID- 30215864
TI  - Neural Basis of Touch and Proprioception in Primate Cortex.
AB  - The sense of proprioception allows us to keep track of our limb posture and
      movements and the sense of touch provides us with information about objects with
      which we come into contact. In both senses, mechanoreceptors convert the
      deformation of tissues-skin, muscles, tendons, ligaments, or joints-into neural
      signals. Tactile and proprioceptive signals are then relayed by the peripheral
      nerves to the central nervous system, where they are processed to give rise to
      percepts of objects and of the state of our body. In this review, we first
      examine briefly the receptors that mediate touch and proprioception, their
      associated nerve fibers, and pathways they follow to the cerebral cortex. We then
      provide an overview of the different cortical areas that process tactile and
      proprioceptive information. Next, we discuss how various features of objects
      their shape, motion, and texture, for example-are encoded in the various cortical
      fields, and the susceptibility of these neural codes to attention and other forms
      of higher-order modulation. Finally, we summarize recent efforts to restore the
      senses of touch and proprioception by electrically stimulating somatosensory
      cortex. (c) 2018 American Physiological Society. Compr Physiol 8:1575-1602, 2018.

PMID- 30215865
TI  - Gastrointestinal Handling of Water-Soluble Vitamins.
AB  - Nine compounds are classified as water-soluble vitamins, eight B vitamins and one
      vitamin C. The vitamins are mandatory for the function of numerous enzymes and
      lack of one or more of the vitamins may lead to severe medical conditions. All
      the vitamins are supplied by food in microgram to milligram quantities and in
      addition some of the vitamins are synthesized by the intestinal microbiota. In
      the gastrointestinal tract, the vitamins are liberated from binding proteins and
      for some of the vitamins modified prior to absorption. Due to their solubility in
      water, they all require specific carriers to be absorbed. Our current knowledge
      concerning each of the vitamins differs in depth and focus and is influenced by
      the prevalence of conditions and diseases related to lack of the individual
      vitamin. Because of that we have chosen to cover slightly different aspects for
      the individual vitamins. For each of the vitamins, we summarize the physiological
      role, the steps involved in the absorption, and the factors influencing the
      absorption. In addition, for some of the vitamins, the molecular base for
      absorption is described in details, while for others new aspects of relevance for
      human deficiency are included. (c) 2018 American Physiological Society. Compr
      Physiol 8:1291-1311, 2018.

PMID- 30215866
TI  - Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver.
AB  - Iron and copper have similar physiochemical properties; thus, physiologically
      relevant interactions seem likely. Indeed, points of intersection between these
      two essential trace minerals have been recognized for many decades, but
      mechanistic details have been lacking. Investigations in recent years have
      revealed that copper may positively influence iron homeostasis, and also that
      iron may antagonize copper metabolism. For example, when body iron stores are
      low, copper is apparently redistributed to tissues important for regulating iron
      balance, including enterocytes of upper small bowel, the liver, and blood. Copper
      in enterocytes may positively influence iron transport, and hepatic copper may
      enhance biosynthesis of a circulating ferroxidase, ceruloplasmin, which
      potentiates iron release from stores. Moreover, many intestinal genes related to
      iron absorption are transactivated by a hypoxia-inducible transcription factor,
      hypoxia-inducible factor-2alpha (HIF2alpha), during iron deficiency.
      Interestingly, copper influences the DNA-binding activity of the HIF factors,
      thus further exemplifying how copper may modulate intestinal iron homeostasis.
      Copper may also alter the activity of the iron-regulatory hormone hepcidin.
      Furthermore, copper depletion has been noted in iron-loading disorders, such as
      hereditary hemochromatosis. Copper depletion may also be caused by high-dose iron
      supplementation, raising concerns particularly in pregnancy when iron
      supplementation is widely recommended. This review will cover the basic
      physiology of intestinal iron and copper absorption as well as the metabolism of
      these minerals in the liver. Also considered in detail will be current
      experimental work in this field, with a focus on molecular aspects of intestinal
      and hepatic iron-copper interplay and how this relates to various disease states.
      (c) 2018 American Physiological Society. Compr Physiol 8:1433-1461, 2018.

PMID- 30215867
TI  - Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease:
      The Janitor Is the Undercover Boss.
AB  - Adaptive responses that counter starvation have evolved over millennia to permit
      organismal survival, including changes at the level of individual organelles,
      cells, tissues, and organ systems. In the past century, a shift has occurred away
      from disease caused by insufficient nutrient supply toward overnutrition, leading
      to obesity and diabetes, atherosclerosis, and cardiometabolic disease. The burden
      of these diseases has spurred interest in fasting strategies that harness
      physiological responses to starvation, thus limiting tissue injury during
      metabolic stress. Insights gained from animal and human studies suggest that
      intermittent fasting and chronic caloric restriction extend lifespan, decrease
      risk factors for cardiometabolic and inflammatory disease, limit tissue injury
      during myocardial stress, and activate a cardioprotective metabolic program.
      Acute fasting activates autophagy, an intricately orchestrated lysosomal
      degradative process that sequesters cellular constituents for degradation, and is
      critical for cardiac homeostasis during fasting. Lysosomes are dynamic cellular
      organelles that function as incinerators to permit autophagy, as well as
      degradation of extracellular material internalized by endocytosis,
      macropinocytosis, and phagocytosis. The last decade has witnessed an explosion of
      knowledge that has shaped our understanding of lysosomes as central regulators of
      cellular metabolism and the fasting response. Intriguingly, lysosomes also store
      nutrients for release during starvation; and function as a nutrient sensing
      organelle to couple activation of mammalian target of rapamycin to nutrient
      availability. This article reviews the evidence for how the lysosome, in the
      guise of a janitor, may be the "undercover boss" directing cellular processes for
      beneficial effects of intermittent fasting and restoring homeostasis during feast
      and famine. (c) 2018 American Physiological Society. Compr Physiol 8:1639-1667,
      2018.

PMID- 30215868
TI  - Inflammation and microbiota fingerprint: Delphi's oracle for NAFLD-related HCC?
AB  - Dysfunctions of the gut bacterial flora have an important impact on liver
      diseases. Quantitative or qualitative ruptures of intestinal homeostasis,
      collectively termed dysbiosis, constitute an increasingly recognized associated
      factor for chronic liver diseases, including non-alcoholic fatty liver disease
      (NAFLD). The evidence that gut maladaptation is a common feature in NAFLD
      settings led Ponziani et al. to investigate whether specific variations of the
      flora and inflammatory cues are enriched in NAFLD patients presenting with HCC
      (Ponziani et al. this issue). This article is protected by copyright. All rights
      reserved.

PMID- 30215869
TI  - Angina bullosa haemorrhagica-like lesions in pemphigus vulgaris.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to describe a previously
      unreported association of oral pemphigus vulgaris with short-lived blood-filled
      painless blisters resembling angina bullosa haemorrhagica (ABH). METHODS: A cross
      sectional study of consecutive patients with Pemphigus vulgaris. All patients
      were examined for the presence of ABH-like lesions, and demographic, clinical and
      histopathological data were collected. Histopathological examination was
      performed when feasible. RESULTS: A total of 318 with pemphigus vulgaris were
      included (63.5% female, mean age: 46 years). ABH-like lesions were present in 82
      (25.8%) patients, commonly observed in the buccal mucosa (47, 57.3%) followed by
      the palate (15, 18.3%). All patients had normal platelet counts with no evidence
      of bleeding diathesis. Biopsies of the ABH-like lesions showed suprabasal clefts
      in four of six samples. ABH-like lesions were significantly associated with
      partial remission of pemphigus vulgaris (47.5%, P = 0.002) and the use of
      intraoral steroids (P = 0.001, odds ratio: 5.9 [95% confidence interval: 2.5
      13.6]). CONCLUSION: ABH-like lesions may represent a transient or abortive form
      of oral pemphigus vulgaris and tend to have a benign and self-limiting nature.

PMID- 30215870
TI  - Dynactin is involved in Lewy body pathology.
AB  - Dynactin forms a protein complex with dynein that retrogradely transports cargo
      along microtubules. Dysfunction of this dynein-dynactin complex causes several
      neurodegenerative diseases such as Perry syndrome, motor neuron diseases and
      progressive supranuclear palsy. Recently, we reported colocalization of
      phosphorylated alpha-synuclein (p-SNCA) and the largest subunit of dynactin
      (DCTN1) in Lewy body (LB)-like structures in Perry syndrome. Previous reports
      have not focused on the relationship between dynactin and synucleinopathies.
      Thus, we examined autopsied human brains from patients with Parkinson's disease,
      dementia with LBs, and multiple system atrophy using immunohistochemistry for p
      SNCA, DCTN1, dynactin 2 (DCTN2, dynamitin) and dynein cytoplasmic 1 intermediate
      chain 1 (DYNC1I1). We also examined microtubule affinity-regulating kinases
      (MARKs), which phosphorylate microtubule-associated proteins and trigger
      microtubule disruption. Both brainstem-type and cortical LBs were immunopositive
      for DCTN1, DCTN2, DYNC1I1 and p-MARK and their staining often overlapped with p
      SNCA. Lewy neurites were also immunopositive for DCTN1, DCTN2 and DYNC1I1.
      However, p-SNCA-positive inclusions of multiple system atrophy, which included
      both glial and neuronal cytoplasmic inclusions, were immunonegative for DCTN1,
      DCTN2, DYNC1I1 and p-MARK. Thus, immunohistochemistry for dynein-dynactin complex
      molecules, especially DCTN1, can clearly distinguish LBs from neuronal
      cytoplasmic inclusions. Our results suggest that dynactin is closely associated
      with LB pathology.

PMID- 30215871
TI  - Recovery and forensic care: Recent advances and future directions.

PMID- 30215872
TI  - RNA versus DNA G-Quadruplex: The Origin of Increased Stability.
AB  - DNA quadruplexes have been the subject of investigation because of their
      biological relevance and because of their potential application in supramolecular
      chemistry. Similarly, RNA quadruplexes are now gaining increasing attention.
      Although DNA and RNA quadruplexes are structurally very similar, the latter show
      higher stability. In this study we report dispersion-corrected density functional
      theory (DFT-D) quantum chemical calculations that were undertaken to understand
      the difference in stabilities of RNA and DNA quadruplexes. The smallest
      meaningful model of a stack of quartets, interacting with alkali metal cations,
      was simulated in an aqueous environment. The energy decomposition analysis allows
      for in-depth examination of the interaction energies, emphasising the role of
      noncovalent interactions and better electrostatics in determining RNA-GQs higher
      stabilities, particularly pinpointing the role of the extra 2'-OH groups.
      Furthermore, our computations present new insights on why the cation is required
      for self-assembly: unexpectedly the cation is not necessary to relieve the
      repulsion between the oxygen atoms in the central cavity, but it is needed to
      overcome the entropic penalty.

PMID- 30215873
TI  - Work environment risks for health care workers with cystic fibrosis.
AB  - In Australia and New Zealand, >50% of people with cystic fibrosis (CF) are adults
      and many of these people are pursuing vocational training and undertaking paid
      employment. More than 6% of adults with CF are working in health care. There is
      limited guidance in literature to support health care workers with CF (HCWcf) in
      training and in employment to support safe practice and to provide protection for
      themselves and their patients from the acquisition of health care associated
      infection. A multidisciplinary team of CF and Infectious Disease Clinicians,
      Infection Prevention and Control Practitioners, HCWcf, academic experts in
      medical ethics and representatives from universities, appraised the available
      evidence on the risk posed to and by HCWcf. Specific recommendations were made
      for HCWcf, CF health care teams, hospitals and universities to support the safe
      practice and appropriate support for HCWcf.

PMID- 30215874
TI  - Dynamical ventral tegmental area circuit mechanisms of alcohol-dependent dopamine
      release.
AB  - A large body of data has identified numerous molecular targets through which
      ethanol (EtOH) acts on brain circuits. Yet how these multiple mechanisms interact
      to result in dysregulated dopamine (DA) release under the influence of alcohol in
      vivo remains unclear. In this manuscript, we delineate potential circuit-level
      mechanisms responsible for EtOH-dependent dysregulation of DA release from the
      ventral tegmental area (VTA) into its projection areas. For this purpose, we
      constructed a circuit model of the VTA that integrates realistic Glutamatergic
      (Glu) inputs and reproduces DA release observed experimentally. We modelled the
      concentration-dependent effects of EtOH on its principal VTA targets. We
      calibrated the model to reproduce the inverted U-shape dose dependence of DA
      neuron activity on EtOH concentration. The model suggests a primary role of EtOH
      induced boost in the Ih and AMPA currents in the DA firing-rate/bursting
      increase. This is counteracted by potentiated GABA transmission that decreases DA
      neuron activity at higher EtOH concentrations. Thus, the model connects well
      established in vitro pharmacological EtOH targets with its in vivo influence on
      neuronal activity. Furthermore, we predict that increases in VTA activity
      produced by moderate EtOH doses require partial synchrony and relatively low
      rates of the Glu afferents. We propose that the increased frequency of transient
      (phasic) DA peaks evoked by EtOH results from synchronous population bursts in
      VTA DA neurons. Our model predicts that the impact of acute ETOH on dopamine
      release is critically shaped by the structure of the cortical inputs to the VTA.

PMID- 30215875
TI  - Commentary on Border et al. (2018): The public health burden of conduct disorder,
      early mortality and criminal justice involvement.

PMID- 30215876
TI  - Efficacy of pelvic floor training with surface electromyography feedback for
      female stress urinary incontinence.
AB  - AIMS: The aim of the study is to compare the efficacy of an 8-week pelvic floor
      muscle training program with surface electromyography feedback, performed in
      different body positions (supine, sitting, and standing), in women with stress
      urinary incontinence. DESIGN: This is a prospective observational study performed
      January 2014 to May 2016. METHODS: The training program was performed by 110
      women with stress urinary incontinence, each completing 4 individual training
      sessions. The main outcome was the electromyography activity of the pelvic floor
      muscles and of the synergistic abdominal muscles. Outcome measures were evaluated
      at 4 time points, namely at baseline and at 2, 4, and 8 weeks of training.
      RESULTS: A notable effect of training was identified at week 2, which was
      sustained through to week 8. Training yielded a significant improvement in
      increased sustained voluntary contraction of the pelvic floor muscles in all 3
      positions. The efficacy of training was influenced by the duration of training,
      age, body mass index, and history of vaginal delivery. CONCLUSION: Training of
      the pelvic floor muscles, with positive reinforcement by surface electromyography
      feedback of the pelvic floor muscles and of the synergistic abdominal muscles,
      was effective for the treatment of stress urinary incontinence in women and
      should be considered as a feasible option by healthcare providers.

PMID- 30215877
TI  - Specific and Oriented Encapsulation of Fullerene C70 into a Supramolecular Double
      Decker Cage Composed of Shape-Persistent Macrocycles.
AB  - An efficient strategy for the specific recognition of ellipsoidal fullerenes uses
      molecular containers with well-designed three-dimensional (3D) nanospaces. We
      describe the synthesis of a supramolecular double-decker cage composed of shape
      persistent metallomacrocycles and pillar ligands. A discrete 3D nanospace was
      built within the molecular framework of the shape-persistent-macrocycle/bidentate
      pillar molecule. The single-crystal structure of the supramolecular cage reveals
      a uniquely shaped inner cavity with a size and net volume (>670 A3 ) that are
      well matched to the shape and size of C70 . The cage exhibited higher selectivity
      for C70 over C60 , the smaller carbon allotrope. We suggest that such C70 
      selective recognition is derived from multiple CH-pi interactions between
      hydrogen atoms inside the cage and C70 .

PMID- 30215878
TI  - MicroRNA Isolation from Plasma for Real-Time qPCR Array.
AB  - MicroRNAs are short non-coding RNAs that regulate gene expression at the post
      transcriptional level by mRNA degradation or suppression of translation. Their
      stability in plasma makes them attractive biomarkers. Since many plasma microRNA
      isolation procedures exist and the yield can be highly variable, we recently
      optimized the microRNA isolation and preamplification procedure using the mirVana
      PARIS kit (Thermo Fisher Scientific) for miRNA quantification with TaqMan Low
      Density Arrays in plasma samples. The method here is slightly modified from the
      original procedure supplied by Thermo Fisher. Based on our findings,
      recommendations are the following: (1) use Arabidopsis thaliana (Ath) miR-159a as
      spike-in control, (2) use a 100-ul elution volume during RNA isolation, and (3)
      add a preamplification step without dilution of the preamplification product. In
      this article we provide a step-by-step microRNA isolation and quantification
      procedure using human plasma samples for TaqMan Low Density Arrays. (c) 2018 by
      John Wiley & Sons, Inc.

PMID- 30215879
TI  - Enhanced gross primary production and evapotranspiration in juniper-encroached
      grasslands.
AB  - Woody plant encroachment (WPE) into grasslands has been occurring globally and
      may be accelerated by climate change in the future. This land cover change is
      expected to alter the carbon and water cycles, but it remains uncertain how and
      to what extent the carbon and water cycles may change with WPE into grasslands
      under current climate. In this study, we examined the difference of vegetation
      indices (VIs), evapotranspiration (ET), gross primary production (GPP), and solar
      induced chlorophyll fluorescence (SIF) during 2000-2010 between grasslands and
      juniper-encroached grasslands. We also quantitatively assessed the changes of GPP
      and ET for grasslands with different proportions of juniper encroachment (JWPE).
      Our results suggested that JWPE increased the GPP, ET, greenness-related VIs, and
      SIF of grasslands. Mean annual GPP and ET were, respectively, ~55% and ~45%
      higher when grasslands were completely converted into juniper forests under
      contemporary climate during 2000-2010. The enhancement of annual GPP and ET for
      grasslands with JWPE varied over years ranging from about +20% GPP (~+30% for ET)
      in the wettest year (2007) to about twice as much GPP (~+55% for ET) in the
      severe drought year (2006) relative to grasslands without encroachment.
      Additionally, the differences in GPP and ET showed significant seasonal dynamics.
      During the peak growing season (May-August), GPP and ET for grasslands with JWPE
      were ~30% and ~40% higher on average. This analysis provided insights into how
      and to what degree carbon and water cycles were impacted by JWPE, which is vital
      to understanding how JWPE and ecological succession will affect the regional and
      global carbon and water budgets in the future.

PMID- 30215881
TI  - A practical guide to pre-trial simulations for Bayesian adaptive trials using SAS
      and BUGS.
AB  - It is often unclear what specific adaptive trial design features lead to an
      efficient design which is also feasible to implement. Before deciding on a
      particular design, it is generally advisable to carry out a simulation study to
      characterise the properties of candidate designs under a range of plausible
      assumptions. The implementation of such pre-trial simulation studies presents
      many challenges and requires considerable statistical programming effort and
      time. Despite the scale and complexity, there is little existing literature to
      guide the implementation of such projects using commonly available software. This
      Teacher's Corner article provides a practical step-by-step guide to implementing
      such simulation studies including how to specify and fit a Bayesian model in
      WinBUGS or OpenBUGS using SAS, and how results from the Bayesian analysis may be
      pulled back into SAS and used for adaptation of allocation probabilities before
      simulating subsequent stages of the trial. The interface between the two software
      platforms is described in detail along with useful tips and tricks. A key
      strength of our approach is that the entire exercise can be defined and
      controlled from within a single SAS program.

PMID- 30215880
TI  - Engineered Biosynthesis of beta-Alkyl Tryptophan Analogues.
AB  - Noncanonical amino acids (ncAAs) with dual stereocenters at the alpha and beta
      positions are valuable precursors to natural products and therapeutics. Despite
      the potential applications of such bioactive beta-branched ncAAs, their
      availability is limited due to the inefficiency of the multistep methods used to
      prepare them. Herein we report a stereoselective biocatalytic synthesis of beta
      branched tryptophan analogues using an engineered variant of Pyrococcus furiosus
      tryptophan synthase (PfTrpB), PfTrpB7E6 . PfTrpB7E6 is the first biocatalyst to
      synthesize bulky beta-branched tryptophan analogues in a single step, with
      demonstrated access to 27 ncAAs. The molecular basis for the efficient catalysis
      and broad substrate tolerance of PfTrpB7E6 was explored through X-ray
      crystallography and UV/Vis spectroscopy, which revealed that a combination of
      active-site and remote mutations increase the abundance and persistence of a key
      reactive intermediate. PfTrpB7E6 provides an operationally simple and
      environmentally benign platform for the preparation of beta-branched tryptophan
      building blocks.

PMID- 30215882
TI  - Tuning Charge Transport in Aromatic-Ring Single-Molecule Junctions via Ionic
      Liquid Gating.
AB  - Achieving gate control with atomic precision, which is crucial to the transistor
      performance on the smallest scale, remains a challenge. Herein we report a new
      class of aromatic-ring molecular nanotransistors based on graphene-molecule
      graphene single-molecule junctions by using an ionic-liquid gate. Experimental
      phenomena and theoretical calculations confirm that this ionic-liquid gate can
      effectively modulate the alignment between molecular frontier orbitals and the
      Fermi energy level of graphene electrodes, thus tuning the charge-transport
      properties of the junctions. In addition, with a small gate voltage (|VG |<=1.5
      V) ambipolar charge transport in electrochemically inactive molecular systems (EG
      >3.5 eV) is realized. These results offer a useful way to build high-performance
      single-molecule transistors, thus promoting the prospects for molecularly
      engineered electronic devices.

PMID- 30215883
TI  - Should we be dishing out drugs whilst in the midst of dialogue?

PMID- 30215884
TI  - Transformative elements of intercultural education for Japanese nursing students.
AB  - There has been little research exploring Japanese nursing students' experiences
      of having Western instructors in their nursing programs. The purpose of the
      present study was to describe Japanese nursing students' lived experiences of
      being taught by foreign faculty. A qualitative design using an interpretive
      phenomenology approach was used with purposeful sampling. Graduate and
      undergraduate nursing students (n = 13), who had the experience of being taught
      by a foreign faculty member for at least one semester, were recruited. Six themes
      emerged that suggested the participants went through an evolutionary process as
      they worked to understand and make meaning of these intercultural experiences:
      struggling with uncertainty, working to understand, discovering differences in
      teaching styles, opening my eyes to the world, thinking differently now, and
      wanting to know more. The work students must do to understand foreign teachers
      influences what they are able to learn, and must be taken into consideration by
      both faculty and students. To fully realize meaningful teaching outcomes within
      this intercultural context, it is essential that students have sustained exposure
      to foreign faculty.

PMID- 30215885
TI  - Synthesis of gamma,gamma-Disubstituted Butenolides through a Doubly Vinylogous
      Organocatalytic Cycloaddition.
AB  - A novel organocatalytic approach to gamma,gamma-disubstituted butenolides is
      described. It is based on a fully site-selective functionalization of 5
      alkylidenefuran-2(5H)-ones via trienamine-mediated [4+2]-cycloaddition with
      alpha,beta,gamma,delta-diunsaturated aldehydes. The developed methodology
      proceeds with excellent stereocontrol and constitutes a unique example of
      trienamine chemistry with vinylogous dienophiles. Importantly, the reaction has
      very broad scope and allows for the introduction of substituents also in the
      alpha- or the beta-position of the butenolide ring. Usefulness of the products
      obtained has been confirmed in the intramolecular Stetter reaction leading to
      polycyclic product.

PMID- 30215886
TI  - Efficient Photoelectrochemical Water Oxidation on Hematite with Fluorine-Doped
      FeOOH and FeNiOOH as Dual Cocatalysts.
AB  - An effective cocatalyst is usually required to improve the performance of
      photoelectrochemical (PEC) water splitting catalysts. A fluorine-doped FeOOH
      (F:FeOOH) cocatalyst on a hematite photoanode was used to lower the onset
      potential by 140 mV and significantly improve the PEC performance. Moreover, a
      more effective dual cocatalytic system was prepared by subsequent loading of a
      FeNiOOH cocatalyst, which resulted in a further decrease of the onset potential
      by 270 mV. The final onset potential of the Fe2 O3 /F:FeOOH/FeNiOOH photoanode
      was lowered to 0.45 V versus the reversible hydrogen electrode (RHE), which is
      one of the lowest onset potential values ever reported for hematite photoanodes.
      The photocurrent also dramatically increased by a factor of approximately 3 to
      0.9 mA cm-2 at 1.0 V versus RHE. Based on the structural, chemical, and
      electrochemical impedance spectroscopy characterization, the enhanced performance
      was attributed to the F:FeOOH overlayer, which reduced the surface recombination
      and accelerated the oxygen evolution reaction activity, and the FeNiOOH
      cocatalyst, which further enhanced the reaction kinetics. The facile preparation
      of the F:FeOOH cocatalyst and the design of the dual cocatalytic system will
      allow the development of high-performance hematite photoanodes.

PMID- 30215887
TI  - Firearm Violence: A Global Priority for Nursing Science.
AB  - PURPOSE: This purpose of this article is to frame firearm violence as a health
      and public health problem, to illustrate the magnitude of the problem, to examine
      factors that increase the risk to be injured by a firearm, or conversely, that
      confer protection, and to identify relevant priority areas for nursing science.
      ORGANIZING CONSTRUCT: Firearm violence results in physical and psychological
      injuries and is a global health priority. Firearm violence is categorized as
      intentional (interpersonal and self-inflicted) and unintentional (interpersonal
      and self-inflicted) and accounts for an estimated 196,000 to 220,000 nonconflict
      deaths annually. METHODS: We reviewed the theoretical and scientific literature
      to analyze the magnitude and geographic distribution of firearm violence, the
      factors associated with firearm injury, the consequences of firearm violence, and
      areas where nursing science can make an impact on prevention, outcomes, and
      recovery. FINDINGS: Firearm violence is a significant public health problem that
      affects the health of individuals, families, and communities. The burdens and
      contributors to firearm violence vary worldwide, making it important to
      understand the local context of this global phenomenon. Relevant areas of inquiry
      span primary prevention focusing on individual and environmental risk factors;
      and focus on managing the physical and psychological consequences postinjury; and
      mitigating long-term consequences of firearm violence. CONCLUSIONS: Reducing the
      global burden of firearm violence and improving the health and safety of
      individuals, families, and communities provide compelling reasons to integrate
      this area into nursing science. CLINICAL RELEVANCE: The goals of nursing are to
      keep people healthy and safe and to help return those injured to their optimal
      levels of health and well-being. Understanding the factors that come together to
      injure people with a firearm in various physical, social, economic, and cultural
      environments positions nurses to both extend the dialogue beyond pro-gun versus
      anti-gun and to design and carry out rigorous studies to reduce firearm violence.

PMID- 30215888
TI  - First descriptions of tuberous sclerosis by Desire-Magloire Bourneville (1840
      1909).

PMID- 30215890
TI  - Diagnosis of Acute Coronary Syndrome.

PMID- 30215889
TI  - Multicolor Fluorescence In Situ Hybridization (FISH) Approaches for Simultaneous
      Analysis of the Entire Human Genome.
AB  - Analysis of the organization of the human genome is vital for understanding
      genetic diversity, human evolution, and disease pathogenesis. A number of
      approaches, such as multicolor fluorescence in situ hybridization (FISH) assays,
      cytogenomic microarray (CMA), and next-generation sequencing (NGS) technologies,
      are available for simultaneous analysis of the entire human genome. Multicolor
      FISH-based spectral karyotyping (SKY), multiplex FISH (M-FISH), and Rx-FISH may
      provide rapid identification of interchromosomal and intrachromosomal
      rearrangements as well as the origin of unidentified extrachromosomal elements.
      Recent advances in molecular cytogenetics have made it possible to efficiently
      examine the entire human genome in a single experiment at much higher resolution
      and specificity using CMA and NGS technologies. Here, we present an overview of
      the approaches available for genome-wide analyses. (c) 2018 by John Wiley & Sons,
      Inc.

PMID- 30215891
TI  - Diabetes: ADA Releases Revised Position Statement on Standards of Medical Care.

PMID- 30215892
TI  - Can My Primary Care Doctor Treat My Cancer?

PMID- 30215893
TI  - Interventions for Treatment of Overweight and Obese Children.

PMID- 30215894
TI  - Chronic Nonallergic Rhinitis.
AB  - Chronic nonallergic rhinitis encompasses a group of rhinitis subtypes without
      allergic or infectious etiologies. Although chronic nonallergic rhinitis
      represents about one-fourth of rhinitis cases and impacts 20 to 30 million
      patients in the United States, its pathophysiology is unclear and diagnostic
      testing is not available. Characteristics such as no evidence of allergy or
      defined triggers help define clinical subtypes. There are eight subtypes with
      overlapping presentations, including nonallergic rhinopathy, nonallergic rhinitis
      with nasal eosinophilia syndrome, atrophic rhinitis, senile or geriatric
      rhinitis, gustatory rhinitis, drug-induced rhinitis, hormonal rhinitis, and
      occupational rhinitis. Treatment is symptom-driven and similar to that of
      allergic rhinitis. Patients should avoid known triggers when possible. First-line
      therapies include intranasal corticosteroids, intranasal antihistamines, and
      intranasal ipratropium. Combination therapy with decongestants and first
      generation antihistamines can be considered if monotherapy does not adequately
      control symptoms. Nasal irrigation and intranasal capsaicin may be helpful but
      need further investigation.

PMID- 30215895
TI  - Food Insecurity: How You Can Help Your Patients.

PMID- 30215897
TI  - Treatment Duration for Etonogestrel Implant.

PMID- 30215898
TI  - High Demand, Low Supply: Health Centers and the Recruitment of Family Physicians.

PMID- 30215899
TI  - The Role of Proton Pump Inhibitor Therapy in Patients with Functional Dyspepsia.

PMID- 30215900
TI  - A Persistent Lip Ulcer.

PMID- 30215902
TI  - Terbinafine for Onychomycosis.

PMID- 30215901
TI  - Rheumatologic Tests: A Primer for Family Physicians.
AB  - Patients with a suspected connective tissue disorder should undergo serologic
      testing to confirm the diagnosis and, in some cases, to monitor disease activity
      and predict flares. Patients with suspected systemic lupus erythematosus should
      be tested for antinuclear antibodies. However, antinuclear antibodies are not
      specific and may be present in many other connective tissue disorders and
      nonrheumatologic diseases. Thus, patients with suspected systemic lupus
      erythematosus should undergo further testing to confirm the diagnosis. Patients
      with Sjogren syndrome may have a positive antinuclear antibody titer, but often
      also have positive anti-Sjogren antigen A or B results. Similarly, antinuclear
      antibodies can be present in patients with scleroderma, mixed connective tissue
      disease, and dermatomyositis or polymyositis. Additional tests are needed to help
      confirm the diagnosis. In patients with findings of rheumatoid arthritis, a
      positive rheumatoid factor titer suggests the diagnosis, but as with antinuclear
      antibodies, it is not specific and can occur in other conditions. Rheumatoid
      factor can also be negative in patients with rheumatoid arthritis. A positive
      anticyclic citrullinated peptide antibody titer is more specific for rheumatoid
      arthritis and can help confirm the diagnosis. Physicians should order these
      serologic tests only when patients have a high pretest probability of a specific
      connective tissue disorder.

PMID- 30215903
TI  - Type 1 Diabetes: Management Strategies.
AB  - There is considerable benefit of tight glucose control in patients with type 1
      diabetes mellitus. Tight blood glucose control dramatically decreases the
      incidence of microvascular and macrovascular complications. Although glycemic
      goals should be individualized, most nonpregnant adults should strive for an A1C
      level less than 7%. Greater frequency of glucose monitoring and continuous
      glucose monitoring are both associated with lower A1C levels. The choice to
      monitor glucose levels via multiple daily capillary blood samples or continuous
      glucose monitoring is based on cost and patient preference. Intensive insulin
      treatment is recommended with a combination of multiple mealtime bolus and basal
      injections or with continuous insulin infusion through an insulin pump. The
      option to administer insulin with multiple daily injections vs. a pump should be
      individualized. Adjunctive medical therapy is under investigation but is not
      currently recommended. All patients with type 1 diabetes should participate in
      diabetes self-management education and develop individualized premeal insulin
      bolus plans under the guidance of a dietitian, if possible. Blood pressure and
      lipid control are important to prevent cardiovascular disease events. Patients
      with type 1 diabetes should have sick-day plans and be able to identify warning
      signs of hypoglycemia and diabetic ketoacidosis. Advances in diabetes care,
      including the bionic pancreas and the closed-loop system of glucose monitoring
      with an automated insulin pump, may have a significant effect on type 1 diabetes
      care in the years ahead.

PMID- 30215904
TI  - Screening and Immunizations for Refugees to the United States.

PMID- 30215905
TI  - The Many Potential Causes of Sudden Cardiac Death in Young Athletes.

PMID- 30215906
TI  - Consider Atlanto-Occipital Joint Dysfunction as a Cause of Secondary Otalgia.

PMID- 30215907
TI  - What You Should Know About Type 1 Diabetes.

PMID- 30215909
TI  - Single Maintenance and Reliever Therapy More Effective Than Inhaled
      Corticosteroids and Beta Agonists for Asthma.

PMID- 30215908
TI  - A Pigmented Thumbnail Lesion.

PMID- 30215910
TI  - Breastfeeding: Common Questions and Answers.
AB  - All major health organizations recommend breastfeeding as the optimal source of
      infant nutrition, with exclusive breastfeeding recommended for the first six
      months of life. After six months, complementary foods may be introduced. Most
      organizations recommend breastfeeding for at least one year, and the World Health
      Organization recommends a minimum of two years. Maternal benefits of
      breastfeeding include decreased risk of breast cancer, ovarian cancer, postpartum
      depression, hypertension, cardiovascular disease, and type 2 diabetes mellitus.
      Infants who are breastfed have a decreased risk of atopic dermatitis and
      gastroenteritis, and have a higher IQ later in life. Additional benefits in
      infants have been noted in observational studies. Clinicians can support
      postdischarge breastfeeding by assessing milk production and milk transfer;
      evaluating an infant's latch to the breast; identifying maternal and infant
      anatomic variations that can lead to pain and poor infant weight gain; knowing
      the indications for frenotomy; and treating common breastfeeding-related
      infections, dermatologic conditions, engorgement, and vasospasm. The best way to
      assess milk supply is by monitoring infant weight and stool output during
      wellness visits. Proper positioning improves latch and reduces nipple pain.
      Frenotomy is controversial but may reduce pain in the short term. The U.S.
      Preventive Services Task Force recommends primary care interventions to support
      breastfeeding and improve breastfeeding rates and duration.

PMID- 30215911
TI  - Deprescribing Antipsychotics for Behavioral and Psychological Symptoms of
      Dementia and Insomnia.

PMID- 30215912
TI  - Crisaborole (Eucrisa) for Mild to Moderate Atopic Dermatitis.

PMID- 30215913
TI  - Evidence-Based Medicine: Common Misconceptions, Barriers, and Practical
      Solutions.

PMID- 30215914
TI  - Febuxostat Increases All-Cause and Cardiovascular Mortality Compared with
      Allopurinol.

PMID- 30215915
TI  - Hemolytic Anemia: Evaluation and Differential Diagnosis.
AB  - Hemolytic anemia is defined by the premature destruction of red blood cells, and
      can be chronic or life-threatening. It should be part of the differential
      diagnosis for any normocytic or macrocytic anemia. Hemolysis may occur
      intravascularly, extravascularly in the reticuloendothelial system, or both.
      Mechanisms include poor deformability leading to trapping and phagocytosis,
      antibody-mediated destruction through phagocytosis or direct complement
      activation, fragmentation due to microthrombi or direct mechanical trauma,
      oxidation, or direct cellular destruction. Patients with hemolysis may present
      with acute anemia, jaundice, hematuria, dyspnea, fatigue, tachycardia, and
      possibly hypotension. Laboratory test results that confirm hemolysis include
      reticulocytosis, as well as increased lactate dehydrogenase, increased
      unconjugated bilirubin, and decreased haptoglobin levels. The direct antiglobulin
      test further differentiates immune causes from nonimmune causes. A peripheral
      blood smear should be performed when hemolysis is present to identify abnormal
      red blood cell morphologies. Hemolytic diseases are classified into
      hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and
      extrinsic nonimmune causes. Extrinsic nonimmune causes include the thrombotic
      microangiopathies, direct trauma, infections, systemic diseases, and oxidative
      insults. Medications can cause hemolytic anemia through several mechanisms. A
      rapid onset of anemia or significant hyperbilirubinemia in the neonatal period
      should prompt consideration of a hemolytic anemia.

PMID- 30215916
TI  - HPV Testing Better Than Cytology for Women Vaccinated Against HPV.

PMID- 30215919
TI  - Screening for Cardiovascular Disease Risk with Electrocardiography.

PMID- 30215917
TI  - Intestinal Obstruction: Evaluation and Management.
AB  - Acute intestinal obstruction occurs when the forward flow of intestinal contents
      is interrupted or impaired by a mechanical cause. It is most commonly induced by
      intra-abdominal adhesions, malignancy, and herniation. The clinical presentation
      generally includes nausea, emesis, colicky abdominal pain, and cessation of
      passage of flatus and stool, although the severity of these clinical symptoms
      varies based on the acuity and anatomic level of obstruction. Abdominal
      distension, tympany to percussion, and high-pitched bowel sounds are classic
      findings. Laboratory evaluation should include a complete blood count, metabolic
      panel, and serum lactate level. Imaging with abdominal radiography or computed
      tomography can confirm the diagnosis and assist in decision making for
      therapeutic planning. Management of uncomplicated obstructions includes
      intravenous fluid resuscitation with correction of metabolic derangements,
      nasogastric decompression, and bowel rest. Patients with fever and leukocytosis
      should receive antibiotic coverage against gram-negative organisms and anaerobes.
      Evidence of vascular compromise or perforation, or failure to resolve with
      adequate nonoperative management is an indication for surgical intervention.

PMID- 30215921
TI  - Violence in the Health Care Setting: What Can We Do?

PMID- 30215920
TI  - Screening for Cardiovascular Disease Risk with Electrocardiography:
      Recommendation Statement.

PMID- 30215922
TI  - Well-Child Visits for Infants and Young Children.
AB  - The well-child visit allows for comprehensive assessment of a child and the
      opportunity for further evaluation if abnormalities are detected. A complete
      history during the well-child visit includes information about birth history;
      prior screenings; diet; sleep; dental care; and medical, surgical, family, and
      social histories. A head-to-toe examination should be performed, including a
      review of growth. Immunizations should be reviewed and updated as appropriate.
      Screening for postpartum depression in mothers of infants up to six months of age
      is recommended. Based on expert opinion, the American Academy of Pediatrics
      recommends developmental surveillance at each visit, with formal developmental
      screening at nine, 18, and 30 months and autism-specific screening at 18 and 24
      months; the U.S. Preventive Services Task Force found insufficient evidence to
      make a recommendation. Well-child visits provide the opportunity to answer
      parents' or caregivers' questions and to provide age-appropriate guidance. Car
      seats should remain rear facing until two years of age or until the height or
      weight limit for the seat is reached. Fluoride use, limiting or avoiding juice,
      and weaning to a cup by 12 months of age may improve dental health. A one-time
      vision screening between three and five years of age is recommended by the U.S.
      Preventive Services Task Force to detect amblyopia. The American Academy of
      Pediatrics guideline based on expert opinion recommends that screen time be
      avoided, with the exception of video chatting, in children younger than 18 months
      and limited to one hour per day for children two to five years of age. Cessation
      of breastfeeding before six months and transition to solid foods before six
      months are associated with childhood obesity. Juice and sugar-sweetened beverages
      should be avoided before one year of age and provided only in limited quantities
      for children older than one year.

PMID- 30215924
TI  - Adherence to CPAP May Make a Difference for Cardiovascular Outcomes in Patients
      with OSA.

PMID- 30215923
TI  - Consider Cardiovascular Risk Factors Before Prescribing Triptans for Migraine.

PMID- 30215925
TI  - Helpful Tips for Breastfeeding.

PMID- 30215926
TI  - Treatment of Seasonal Allergic Rhinitis: A Guideline from the AAAAI/ACAAI Joint
      Task Force on Practice Parameters.

PMID- 30215927
TI  - Cerebrospinal Fluid Biomarkers for Detection of Alzheimer Disease in Patients
      with Mild Cognitive Impairment.

PMID- 30215928
TI  - Combined Inhaled Short-Acting Beta2 Agonist and Anticholinergic Agents for
      Asthma.

PMID- 30215929
TI  - Intracranial Calcifications Discovered During Prolonged New Seizure.

PMID- 30215930
TI  - Diets for Health: Goals and Guidelines.
AB  - Diet is the single most significant risk factor for disability and premature
      death. Patients and physicians often have difficulty staying abreast of diet
      trends, many of which focus primarily on weight loss rather than nutrition and
      health. Recommending an eating style can help patients make positive change.
      Dietary patterns that support health include the Mediterranean diet, the Dietary
      Approaches to Stop Hypertension diet, the 2015 Dietary Guidelines for Americans,
      and the Healthy Eating Plate. These approaches have benefits that include
      prevention of cardiovascular disease, cancer, type 2 diabetes mellitus, and
      obesity. These dietary patterns are supported by strong evidence that promotes a
      primary focus on unprocessed foods, fruits and vegetables, plant-based fats and
      proteins, legumes, whole grains, and nuts. Added sugars should be limited to less
      than 5% to 10% of daily caloric intake. Vegetables (not including potatoes) and
      fruits should make up one-half of each meal. Carbohydrate sources should
      primarily include beans/legumes, whole grains, fruits, and vegetables. An
      emphasis on monounsaturated fats, such as olive oil, avocados, and nuts, and
      omega-3 fatty acids, such as flax, cold-water fish, and nuts, helps prevent
      cardiovascular disease, type 2 diabetes, and cognitive decline. A focus on foods
      rather than macronutrients can assist patients in understanding a healthy diet.
      Addressing barriers to following a healthy diet and utilizing the entire health
      care team can assist patients in following these guidelines.

PMID- 30215931
TI  - Atypical Antipsychotics for Disruptive Behavior Disorders in Children and
      Adolescents.

PMID- 30215932
TI  - How the FDA Ensures High-Quality Generic Drugs.

PMID- 30215933
TI  - High-Dose vs. Standard-Dose Heparin for VTE Prophylaxis in Obese Patients.

PMID- 30215934
TI  - Hyperhidrosis: Management Options.
AB  - Hyperhidrosis is excessive sweating that affects patients' quality of life,
      resulting in social and work impairment and emotional distress. Primary
      hyperhidrosis is bilaterally symmetric, focal, excessive sweating of the axillae,
      palms, soles, or craniofacial region not caused by other underlying conditions.
      Secondary hyperhidrosis may be focal or generalized, and is caused by an
      underlying medical condition or medication use. The Hyperhidrosis Disease
      Severity Scale is a validated survey used to grade the tolerability of sweating
      and its impact on quality of life. The score can be used to guide treatment.
      Topical aluminum chloride solution is the initial treatment in most cases of
      primary focal hyperhidrosis. Topical glycopyrrolate is first-line treatment for
      craniofacial sweating. Botulinum toxin injection (onabotulinumtoxinA) is
      considered first- or second-line treatment for axillary, palmar, plantar, or
      craniofacial hyperhidrosis. Iontophoresis should be considered for treating
      hyperhidrosis of the palms and soles. Oral anticholinergics are useful adjuncts
      in severe cases of hyperhidrosis when other treatments fail. Local microwave
      therapy is a newer treatment option for axillary hyperhidrosis. Local surgery and
      endoscopic thoracic sympathectomy should be considered in severe cases of
      hyperhidrosis that have not responded to topical or medical therapies.

PMID- 30215936
TI  - Oncologic Emergencies: Recognition and Initial Management.
AB  - Most oncologic emergencies can be classified as metabolic, hematologic,
      structural, or treatment related. Tumor lysis syndrome is a metabolic emergency
      that presents as severe electrolyte abnormalities. Stabilization is focused on
      vigorous rehydration, maintaining urine output, and lowering uric acid levels.
      Hypercalcemia of malignancy, which is associated with poor outcomes, is treated
      with aggressive rehydration, intravenous bisphosphonates, and subspecialty
      consultation. Syndrome of inappropriate antidiuretic hormone should be suspected
      if a patient with cancer has hyponatremia. This metabolic condition is treated
      with fluid restriction or hypertonic saline, depending on the speed of
      development. Febrile neutropenia is one of the most common complications related
      to cancer treatment, particularly chemotherapy. It usually requires inpatient
      therapy with rapid administration of empiric antibiotics. Hyperviscosity syndrome
      may present as spontaneous bleeding and neurologic deficits, and is usually
      associated with Waldenstrom macroglobulinemia. Treatment includes plasmapheresis
      followed by targeted chemotherapy. Structural oncologic emergencies are caused by
      direct compression of nontumor structures by metastatic disease. Superior vena
      cava syndrome presents as facial edema with development of collateral venous
      circulation. Intravascular stenting leads to superior patient outcomes and is
      used in addition to oncology-directed chemotherapy and radiation therapy.
      Malignant epidural spinal cord compression is managed in conjunction with
      neurosurgery, but it is classically treated using steroids and/or surgery and
      radiation therapy. Malignant pericardial effusion may be treated with
      pericardiocentesis or a more permanent surgical intervention. Complications of
      cancer treatment are becoming more varied because of the use of standard and
      newer immunologic therapies. Palliative care is increasingly appropriate as a
      part of the team approach for treating patients with cancer.

PMID- 30215937
TI  - NSAIDs for Postpartum Perineal Pain.

PMID- 30215938
TI  - Advocating for Myself: My Journey Through Poststroke Depression.

PMID- 30215939
TI  - Ruling out Pulmonary Embolism in the Primary Care Setting.

PMID- 30215940
TI  - Ultrasound Is Reasonably Accurate in Detecting Synovitis in Patients with
      Rheumatoid Arthritis.

PMID- 30215941
TI  - NNTs Misleading for Onychomycosis Treatments.

PMID- 30215943
TI  - Lymphadenopathy in Children and Young Adults May Be Due to a Periodic Fever
      Syndrome.

PMID- 30215942
TI  - The Need for Systems of Care and a Trauma-Informed Approach to Intimate Partner
      Violence.

PMID- 30215945
TI  - Contraception Should Be Addressed with Women Who Have Sex with Women.

PMID- 30215944
TI  - Cerebrovascular Disease as a Cause of Dizziness.

PMID- 30215946
TI  - Prescribing Cholinesterase Inhibitors for Alzheimer Disease: Timing Matters.

PMID- 30215947
TI  - Nutrition: How to Make Healthier Food Choices.

PMID- 30215948
TI  - Excessive Sweating (Hyperhidrosis).

PMID- 30215949
TI  - Bleeding with Anticoagulants: ACC Releases Expert Consensus Decision Pathway to
      Guide Management.

PMID- 30215950
TI  - Acute Appendicitis: Efficient Diagnosis and Management.
AB  - Appendicitis is one of the most common causes of acute abdominal pain in adults
      and children, with a lifetime risk of 8.6% in males and 6.7% in females. It is
      the most common nonobstetric surgical emergency during pregnancy. Findings from
      the history, physical examination, and laboratory studies aid in the diagnosis of
      acute appendicitis. Right lower quadrant pain, abdominal rigidity, and
      periumbilical pain radiating to the right lower quadrant are the best signs for
      ruling in acute appendicitis in adults. Absent or decreased bowel sounds, a
      positive psoas sign, a positive obturator sign, and a positive Rovsing sign are
      most reliable for ruling in acute appendicitis in children. The Alvarado score,
      Pediatric Appendicitis Score, and Appendicitis Inflammatory Response score
      incorporate common clinical and laboratory findings to stratify patients as low,
      moderate, or high risk and can help in making a timely diagnosis. Recommended
      first-line imaging consists of point-of-care or formal ultrasonography.
      Appendectomy via open laparotomy or laparoscopy is the standard treatment for
      acute appendicitis. However, intravenous antibiotics may be considered first-line
      therapy in selected patients. Pain control with opioids, nonsteroidal anti
      inflammatory drugs, and acetaminophen should be a priority and does not result in
      delayed or unnecessary intervention. Perforation can lead to sepsis and occurs in
      17% to 32% of patients with acute appendicitis. Prolonged duration of symptoms
      before surgical intervention raises the risk. In moderate- to high-risk patients,
      surgical consultation should be accomplished quickly to reduce morbidity and
      mortality resulting from perforation.

PMID- 30215951
TI  - Allergy Testing: Common Questions and Answers.
AB  - An estimated 10% to 30% of the global population has an allergic disease.
      Clinical presentations of allergic diseases, respiratory infections, and
      autoimmune conditions have similar features. Allergy and immunologic testing can
      help clarify the diagnosis and guide treatment. Immediate immunoglobulin E (IgE)
      and delayed T cell-mediated reactions are the main types of allergic responses.
      The allergens suspected in an immediate IgE-mediated response are identified
      through serum IgE-specific antibody or skin testing. For patients with an
      inhalant allergy, skin or IgE-specific antibody testing is preferred. In patients
      with food allergies, eliminating the suspected allergenic food from the diet is
      the initial treatment. If this is ineffective, IgE-specific antibody or skin
      testing can exclude allergens. An oral food challenge should be performed to
      confirm the diagnosis. Patients with an anaphylactic reaction to an insect sting
      should undergo IgE-specific antibody or skin testing. Skin testing for penicillin
      has a high negative predictive value and can help when penicillin administration
      is indicated and there are limited alternatives. Testing for other drug allergies
      has less well-determined sensitivity and specificity, but can guide the
      diagnosis. Patch testing can help identify the allergen responsible for contact
      dermatitis.

PMID- 30215952
TI  - Short Courses of Antibiotics as Effective as Longer Courses for Outpatient
      Infections.

PMID- 30215953
TI  - The Doorknob Phenomenon in Clinical Practice.

PMID- 30215954
TI  - Asymptomatic Hyperpigmented Iris Lesion.

PMID- 30215955
TI  - Evaluating Medical Decision-Making Capacity in Practice.
AB  - Medical decision-making capacity is the ability of a patient to understand the
      benefits and risks of, and the alternatives to, a proposed treatment or
      intervention (including no treatment). Capacity is the basis of informed consent.
      Patients have medical decision-making capacity if they can demonstrate
      understanding of the situation, appreciation of the consequences of their
      decision, and reasoning in their thought process, and if they can communicate
      their wishes. Capacity is assessed intuitively at every medical encounter and is
      usually readily apparent. However, a more formal capacity evaluation should be
      considered if there is reason to question a patient's decision-making abilities.
      Such reasons include an acute change in mental status, refusal of a clearly
      beneficial recommended treatment, risk factors for impaired decision making, or
      readily agreeing to an invasive or risky procedure without adequately considering
      the risks and benefits. Any physician can evaluate capacity, and a structured
      approach is best. Several formal assessment tools are available to help with the
      capacity evaluation. Consultation with a psychiatrist may be helpful in some
      cases, but the final determination on capacity is made by the treating physician.
      If a patient is found not to have capacity, a surrogate decision maker should be
      identified and consulted. If the patient is unable to give consent and
      identifying a surrogate decision maker will result in a delay that might increase
      the risk of death or serious harm, physicians can provide emergency care without
      formal consent.

PMID- 30215957
TI  - PCI Equal to Sham PCI for Exercise Tolerance in Patients with Stable Angina Plus
      Severe CAD.

PMID- 30215958
TI  - Effects of Prenatal Yoga on Labor Pain.

PMID- 30215959
TI  - Procalcitonin to Guide Antibiotic Therapy in Acute Respiratory Infections.

PMID- 30215961
TI  - Surgery Equal to No Surgery for Patients with Subacromial Shoulder Pain.

PMID- 30215960
TI  - Nebulized Hypertonic Saline for Bronchiolitis.

PMID- 30215962
TI  - Individual Behavioral Counseling for Smoking Cessation.

PMID- 30215963
TI  - Staples vs. Sutures After Cesarean Delivery.

PMID- 30215964
TI  - Statins Effective for LDL 190 mg per dL or Higher, Regardless of Risk Level.

PMID- 30215965
TI  - Short Courses of Oral Corticosteroids: Lack of Benefit and Potential Harms for
      Common Acute Conditions.

PMID- 30215966
TI  - Ketogenic Diet an Option for Treating Uncontrolled Epilepsy.

PMID- 30215967
TI  - Tips for Facilitating Lifestyle Changes in Low-Income Communities.

PMID- 30215969
TI  - Delafloxacin (Baxdela) for Skin Infections.

PMID- 30215968
TI  - Bone Cancer: Diagnosis and Treatment Principles.
AB  - Primary bone cancers include osteosarcoma, Ewing sarcoma, and chondrosarcoma.
      They account for less than 1% of diagnosed cancers each year and are associated
      with significant morbidity and mortality. Timely diagnosis is challenging because
      of late patient presentation, nonspecific symptoms that mimic common
      musculoskeletal injuries, and low suspicion by physicians. Plain radiography is
      the preferred diagnostic test. Radiographic suspicion of a bone malignancy should
      prompt quick referral to a cancer center for multidisciplinary care.
      Osteosarcoma, the most common bone cancer, most often occurs in children and
      adolescents. It typically develops in the metaphysis of long bones, specifically
      the distal femur, proximal tibia, and proximal humerus. Metastasis to the lungs
      is common. Use of neoadjuvant and adjuvant chemotherapy, in combination with
      surgery, has improved survival rates to nearly 80% for patients with localized
      disease, and 90% to 95% of patients do not require limb amputation. Ewing sarcoma
      is the second most common bone cancer and is similar to osteosarcoma in terms of
      presenting symptoms, age at occurrence, and treatment. Prognosis for osteosarcoma
      and Ewing sarcoma depends on the presence of metastasis, which lowers the five
      year survival rate to 20% to 30%. Chondrosarcoma is the rarest bone cancer,
      primarily affecting adults older than 40 years. Survival rates are higher because
      most of these tumors are low-grade lesions.

PMID- 30215970
TI  - Medications Ineffective to Prevent Cognitive Decline or Dementia.

PMID- 30215971
TI  - Epistaxis: Outpatient Management.
AB  - Epistaxis is a common emergency encountered by primary care physicians. Up to 60%
      of the general population experience epistaxis, and 6% seek medical attention for
      it. More than 90% of cases arise from the anterior nasal circulation, and most
      treatments can be easily performed in the outpatient setting. Evaluation of a
      patient presenting with epistaxis should begin with assessment of vital signs,
      mental status, and airway patency. When examining the nose, a nasal speculum and
      a good light source, such as a headlamp, can be useful. Compressive therapy is
      the first step to controlling anterior epistaxis. Oxymetazoline nasal spray or
      application of cotton soaked in oxymetazoline or epinephrine 1: 1,000 may be
      useful adjuncts to compressive therapy. Directive nasal cautery, most commonly
      using silver nitrate, can be used to control localized continued bleeding or
      prominent vessels that are the suspected bleeding source. Finally, topical
      therapy and nasal packing can be used if other methods are unsuccessful. Compared
      with anterior epistaxis, posterior epistaxis is more likely to require
      hospitalization and twice as likely to need nasal packing. Posterior nasal
      packing is often associated with pain and a risk of aspiration if it is
      dislodged. After stabilization, patients with posterior packing often require
      referral to otolaryngology or the emergency department for definitive treatments.

PMID- 30215972
TI  - Interventions to Prevent Falls in Community-Dwelling Older Adults: Recommendation
      Statement.

PMID- 30215974
TI  - Aspirin No Different Than Rivaroxaban for Prevention of VTE After TKA or THA.

PMID- 30215973
TI  - Preoperative Assessment in Older Adults: A Comprehensive Approach.
AB  - Surgical outcomes are significantly influenced by patients' overall health,
      function, and life expectancy. A comprehensive geriatric preoperative assessment
      of older adults requires expanding beyond an organ-based or disease-based
      assessment. At a preoperative visit, it is important to establish the patient's
      goals and preferences, and to determine whether the risks and benefits of surgery
      match these goals and preferences. These discussions should cover the possibility
      of resuscitation and ventilator support, prolonged rehabilitation, and loss of
      independence. The assessment should include evaluation of medical comorbidities,
      cognitive function, decision-making capacity, functional status, fall risk,
      frailty, nutritional status, and potentially inappropriate medication use.
      Problems identified in any of these key areas are associated with an increased
      risk of postoperative complications, institutionalization, functional decline,
      and, in some cases, mortality. If a patient elects to proceed with surgery, the
      risks should be communicated to surgical teams to allow for inpatient
      interventions that lower the risk of postoperative complications and functional
      decline, such as early mobilization and limiting medications that can cause
      delirium. Alcohol abuse and smoking are associated with increased rates of
      postoperative complications, and physicians should discuss cessation with
      patients before surgery. Physicians should also assess patients' social support
      systems because they are a critical component of discharge planning in this
      population and have been shown to predict 30-day postoperative morbidity.

PMID- 30215976
TI  - Solitary Ulcerated Lesion on the Arm.

PMID- 30215977
TI  - Safe Reduction of Primary Cesarean Births: National Partnership for Maternal
      Safety Releases Consensus Bundle.

PMID- 30215979
TI  - Point-of-Care Ultrasonography in Family Medicine.

PMID- 30215978
TI  - Nutrition in Toddlers.
AB  - The establishment of eating practices that contribute to lifelong nutritional
      habits and overall health begins in toddlerhood. During this time, children
      acquire the motor skills needed to feed themselves and develop preferences that
      affect their food selections. Classifications for faltering weight (also called
      failure to thrive or growth faltering) and overweight are based on World Health
      Organization child growth standards (for children younger than two years) and
      Centers for Disease Control and Prevention growth charts (for children two years
      and older). Breast milk or whole cow's milk should be offered as the primary
      beverage between one and two years of age. Sugar-sweetened beverages should be
      avoided in all toddlers, and water or milk should be offered instead. Allergenic
      foods such as peanuts should be introduced early to infants at higher risk of
      allergies. Vitamin D and iron supplementation may be advisable in certain
      circumstances, but multivitamins and other micronutrient supplements are usually
      unnecessary in healthy children who have a balanced diet and normal growth.
      Optimal food choices for toddlers are fresh foods and minimally processed foods
      with little or no added sugar, salt, or fat (e.g., fruits, vegetables, lean
      protein, seeds, whole grains). Parents and caregivers are responsible for
      modeling healthy food choices and dietary practices, which shape children's food
      preferences and eating behaviors. Parents should avoid practices that lead to
      overeating in toddlers (e.g., feeding to soothe or to get children to sleep,
      providing excessive portions, pushing children to "clean their plates," punishing
      with food, force-feeding, allowing frequent snacks or grazing). In general,
      parents should use the approach of "the parent provides, the child decides," in
      which the parent provides healthy food options, and the child chooses which foods
      to eat and how much.

PMID- 30215981
TI  - Pulmonary Embolism Rule-Out Criteria Reduces the Need for CT Pulmonary
      Angiography in Low-Risk Patients.

PMID- 30215980
TI  - Interventions to Prevent Falls and Fractures in Community-Dwelling Older Adults.

PMID- 30215982
TI  - Identifying Patients with Headache Who Are at Risk of Subarachnoid Hemorrhage.

PMID- 30215983
TI  - Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of
      Fractures in Community-Dwelling Older Adults: Recommendation Statement.

PMID- 30215984
TI  - Systolic Blood Pressure of At Least 140 mm Hg Best Place to Begin Treatment.

PMID- 30215986
TI  - Giving Your Toddler the Best Nutrition.

PMID- 30215985
TI  - Bone Cancer.

PMID- 30215988
TI  - Hepatitis B Virus Vaccination and Screening: Best Practices from the ACP and CDC.

PMID- 30215987
TI  - Top POEMs of 2017 Consistent with the Principles of the Choosing Wisely Campaign.
AB  - This article discusses the POEMs (patient-oriented evidence that matters) of 2017
      judged to be most consistent with the principles of the Choosing Wisely campaign.
      A POEM is a synopsis of a research study that reports patient-oriented outcomes,
      such as improvement in symptoms, quality of life, or mortality; is free of
      important methodologic bias; and recommends a change in practice for many
      physicians. We selected these POEMs through a crowdsourcing strategy of the daily
      POEMs information service for physician-members of the Canadian Medical
      Association. Recommendations are presented from these top POEMs of primary
      research or meta-analysis as interventions to consider avoiding in practice. The
      recommendations cover musculoskeletal conditions (e.g., avoid arthroscopy for
      initial treatment of a meniscal tear), respiratory disease (e.g., avoid screening
      for lung cancer without informing your patient of the risk of a false-positive
      test result), infections (e.g., do not routinely add
      trimethoprim/sulfamethoxazole to cephalexin for nonpurulent uncomplicated
      cellulitis), and cardiovascular disease (e.g., do not prescribe niacin, alone or
      in combination with a statin, to prevent cardiovascular disease). These POEMs
      describe interventions whose benefits are not superior to other options, are
      sometimes more expensive, or put patients at increased risk of harm. Knowing more
      about these POEMs and their connection with the Choosing Wisely campaign will
      help clinicians and their patients engage in conversations that are better
      informed by high-quality evidence.

PMID- 30215989
TI  - Delivering Bad or Life-Altering News.
AB  - Delivering serious, bad, or life-altering news to a patient is one of the most
      difficult tasks physicians encounter. Broadly defined as information that may
      alter a patient's view of his or her future, bad news may include information
      related to a chronic disease (e.g., diabetes mellitus), a life-altering illness
      (e.g., multiple sclerosis), or an injury leading to significant change (e.g., a
      season-ending knee injury). Patients prefer to receive such news in person, with
      the physician's full attention, and in clear, easy-to-understand language with
      adequate time for questions. Most patients prefer to know their diagnosis, but
      the amount of desired details varies among different cultures and by education
      level, age, and sex. The physician should respect the patient's unique
      preferences for receiving bad news. Physicians may experience stress related to
      providing bad news that extends beyond the actual conversation. For example,
      physicians are afraid of eliciting an emotional reaction, being blamed for the
      bad news, and expressing their emotions during the process. Physicians often
      withhold information or are overly optimistic regarding prognosis, but this can
      lead to confusion for patients regarding their condition. There are several
      algorithms available to help guide the physician in the delivery of bad news,
      including the SPIKES protocol (setting, perception, invitation, knowledge,
      emotion, and strategy and summary). Skillful delivery of bad news can provide
      comfort for the patient and family.

PMID- 30215990
TI  - The Risk of Cardiovascular Disease, Fracture, Dementia, and Cancer After Long
      Term Hormone Therapy in Perimenopausal and Postmenopausal Women.

PMID- 30215991
TI  - Lifitegrast Ophthalmic Solution 5% (Xiidra) for Dry Eye Disease.

PMID- 30215992
TI  - Physical Therapy for Low Back Pain.

PMID- 30215993
TI  - Counseling Parents and Adolescents About Marijuana.

PMID- 30215995
TI  - Behavioral Counseling to Prevent Skin Cancer: Recommendation Statement.

PMID- 30215996
TI  - Behavioral Counseling to Prevent Skin Cancer.

PMID- 30215997
TI  - Stimulant and Designer Drug Use: Primary Care Management.
AB  - Approximately 10% of the U.S. population 12 years and older reported using
      illicit substances in 2015. This article reviews the clinical effects and
      treatment of persons who use cocaine, methamphetamines, 3,4
      methylenedioxymethamphetamine (MDMA), synthetic cannabinoids, and synthetic
      cathinones ("bath salts"). Cocaine blocks the reuptake of the monoamine
      transporters dopamine, norepinephrine, and serotonin. Immediate clinical effects
      include increased energy and euphoria, as well as hypertension and arrhythmias.
      Acute myocardial infarction, seizures, hallucinations, hyperthermia, and movement
      disorders are among the possible adverse effects. Like cocaine, methamphetamine
      blocks reuptake of monoamine transporters, but also stimulates dopamine release
      and has a longer duration of action. Methamphetamine misuse is associated with
      severe dental problems. MDMA is a stimulant and psychedelic with a chemical
      structure similar to serotonin. Adverse effects include serotonin syndrome,
      hyponatremia, long-term memory impairment, and mood disorders. Synthetic
      cannabinoids can have a more intense and long-lasting effect than natural
      cannabis. Acute intoxication may cause severe cardiac and respiratory
      complications and seizures. Synthetic cathinones are marketed as cheap
      substitutes for other stimulants. Their effects are similar to those of other
      stimulants, and they are addictive. Psychosocial intervention is the main form of
      treatment for addiction to these substances. Promising therapies include
      disulfiram and substitution therapy for cocaine misuse disorders, and mirtazapine
      for methamphetamine use disorder.

PMID- 30215998
TI  - Lower Extremity Erythema.

PMID- 30215999
TI  - HEART Score for Predicting Adverse Outcomes in Patients with Chest Pain.

PMID- 30216000
TI  - Marijuana: Talking Points for Parents and Teens.

PMID- 30216002
TI  - Meth: What You Should Know.

PMID- 30216001
TI  - Club Drugs: What You Should Know.

PMID- 30216003
TI  - AFP 2018: How We're Doing.

PMID- 30216004
TI  - Antibiotics for Otitis Media in Children.

PMID- 30216005
TI  - Corticosteroids for Sore Throat: BMJ Rapid Recommendation.

PMID- 30216006
TI  - Treatments for de Quervain Tenosynovitis.

PMID- 30216007
TI  - FIT More Acceptable with Better Detection Rate Than gFOBT for Colorectal Cancer
      Screening.

PMID- 30216008
TI  - Drugs for Chronic Idiopathic Constipation Are Similarly Effective.

PMID- 30216009
TI  - Localized Prostate Cancer: Treatment Options.
AB  - In the United States, prostate cancer will be diagnosed in one out of seven men
      in his lifetime. Most cases are localized, and only one in 39 men will die from
      the disease. Prostate cancer is most often detected using serum prostate-specific
      antigen testing. The National Comprehensive Cancer Network guidelines use four
      main factors to stratify risk of disease progression or recurrence and to
      determine the recommended treatment: clinical stage, pathologic grade, prostate
      specific antigen level, and comorbidity-adjusted life expectancy. Radical
      prostatectomy or external beam radiation therapy should be considered for
      patients with high-risk prostate cancer regardless of comorbidity-adjusted life
      expectancy. These treatments are almost equivalent in effectiveness but have
      different adverse effect profiles. Patients who undergo radical prostatectomy are
      more likely to experience urinary incontinence and trouble obtaining or
      sustaining an erection compared with patients who opt for radiation therapy.
      Brachytherapy is an option for patients with low-risk disease and some patients
      with intermediate-risk disease. Active surveillance is an option for patients
      with low-risk and very low-risk disease. With active surveillance, patients are
      closely followed and undergo invasive treatments only if the cancer progresses.
      Prostate cancer progression may be indicated by an increase in the pathologic
      grade, a significant rise in serum prostate-specific antigen level, or an
      abnormality on digital rectal examination.

PMID- 30216010
TI  - Injectable Extended-Release Naltrexone Effective for Opioid Use Disorder.

PMID- 30216013
TI  - Screening for Ovarian Cancer: Recommendation Statement.

PMID- 30216012
TI  - Screening for Ovarian Cancer.

PMID- 30216014
TI  - Oxymetazoline Hydrochloride 1% Cream (Rhofade) for Persistent Facial Erythema
      Associated with Rosacea.

PMID- 30216015
TI  - Identifying Patients with Newly Diagnosed Acute Pulmonary Embolism Who Are at Low
      Risk of Death.

PMID- 30216016
TI  - Recurrent Abdominal Pain in Children.
AB  - Recurrent abdominal pain (RAP) in children is defined as at least three episodes
      of pain that occur over at least three months and affect the child's ability to
      perform normal activities. RAP is most often considered functional (nonorganic)
      abdominal pain, but an organic cause is found in 5% to 10% of cases. Further
      workup is warranted in children who have RAP and fever, vomiting, blood in the
      stool, more than three alarm symptoms, or a history of urinary tract infections.
      Physical examination findings that should prompt further workup include weight
      loss or failure to grow; jaundice; costovertebral tenderness or back pain with
      lower extremity neurologic symptoms; liver, spleen, or kidney enlargement; an
      abdominal mass; or localized tenderness on abdominal examination. Workup may
      include complete blood count, erythrocyte sedimentation rate, C-reactive protein
      level, fecal guaiac testing, fecal ova and parasite testing, or urinalysis.
      Pregnancy testing and screening for sexually transmitted infections should be
      considered in adolescents or if there are concerns about sexual abuse. Abdominal
      radiography can be helpful for diagnosing obstruction or constipation. Abdominal
      ultrasonography identifies an abnormality in up to 10% of children with RAP who
      meet criteria for further workup, compared with 1% of those who do not meet these
      criteria. Functional abdominal pain is a clinical diagnosis and no workup is
      needed. Management of functional abdominal pain focuses on improving quality of
      life, reducing parent and child concerns about the seriousness of the condition,
      and reducing the disability associated with pain rather than complete resolution
      of pain. Although evidence is lacking for most pharmacologic treatments of
      functional abdominal pain, psychological therapies such as cognitive behavior
      therapy and hypnotherapy have been shown to be beneficial.

PMID- 30215625
TI  - Measurement of jet fragmentation in Pb+Pb and pp collisions at sNN=2.76 TeV with
      the ATLAS detector at the LHC.
AB  - The distributions of transverse momentum and longitudinal momentum fraction of
      charged particles in jets are measured in Pb+Pb and pp collisions with the ATLAS
      detector at the LHC. The distributions are measured as a function of jet
      transverse momentum and rapidity. The analysis utilises an integrated luminosity
      of 0.14 nb -1 of Pb+Pb data and 4.0 pb -1 of pp data collected in 2011 and 2013,
      respectively, at the same centre-of-mass energy of 2.76 TeV per colliding nucleon
      pair. The distributions measured in pp collisions are used as a reference for
      those measured in Pb+Pb collisions in order to evaluate the impact on the
      internal structure of jets from the jet energy loss of fast partons propagating
      through the hot, dense medium created in heavy-ion collisions. Modest but
      significant centrality-dependent modifications of fragmentation functions in
      Pb+Pb collisions with respect to those in pp collisions are seen. No significant
      dependence of modifications on jet pT and rapidity selections is observed except
      for the fragments with the highest transverse momenta for which some reduction of
      yields is observed for more forward jets.

PMID- 30216017
TI  - Progressive Rash Involving the Hands and Feet.

PMID- 30216018
TI  - Geriatric Assessment: An Office-Based Approach.
AB  - Family physicians should be proficient in geriatric assessment because, as
      society ages, older adults will constitute an increasing proportion of patients.
      Geriatric assessment evaluates medical, social, and environmental factors that
      influence overall well-being, and addresses functional status, fall risk,
      medication review, nutrition, vision, hearing, cognition, mood, and toileting.
      The Medicare Annual Wellness Visit includes the key elements of geriatric
      assessment performed by family physicians. Comprehensive geriatric assessment can
      lead to early recognition of problems that impair quality of life by identifying
      areas for focused intervention, but a rolling geriatric assessment over several
      visits can also effectively identify subtle or hidden problems. Assessment should
      be tailored to patient goals of care and life expectancy. By asking patients and
      families to self-assess risks using precompleted forms, and by using trained
      office staff to complete validated assessment tools, family physicians can
      maximize efficiency by focusing on identified problems. Fall risk can be assessed
      with a single screening question: "Have you fallen in the past year?" The Beers,
      STOPP (screening tool of older persons' prescriptions), and START (screening tool
      to alert doctors to right treatment) criteria are helpful resources for reviewing
      the appropriateness of medications in older adults. Screening for depression is
      recommended when depression care supports are available; this can be performed
      with a brief two-item screen, the Patient Health Questionnaire-2. Older adults
      should be screened for unintentional weight loss and malnutrition. Although rates
      of hearing loss and vision loss increase with age, there is insufficient evidence
      to recommend screening in asymptomatic individuals. The U.S. Preventive Services
      Task Force advises clinicians to assess cognition when there is suspicion of
      impairment. Urinary incontinence can impair patients' quality of life, and it can
      be assessed with a two-question screening tool. Immunizations and advance care
      planning are also important components of the geriatric assessment.

PMID- 30216022
TI  - Antibiotics for Uncomplicated Skin Abscesses After Incision and Drainage: BMJ
      Rapid Recommendation.

PMID- 30216019
TI  - Assessing Patients' Healthy Literacy Skills Not Necessary in Clinical Practice.

PMID- 30216020
TI  - Prostate Cancer: Making Decisions About Treatment.

PMID- 30216031
TI  - Nonopioids Equivalent to Opioids for Severe Chronic Back, Hip, or Knee Pain with
      Fewer Adverse Outcomes.

PMID- 30216027
TI  - Effect of Dietary Changes on IBS Symptoms.

PMID- 30216029
TI  - Long-Acting Reversible Contraception: Difficult Insertions and Removals.
AB  - The use of long-acting reversible contraception is on the rise across the United
      States and has contributed to a decrease in teen pregnancies. With the increased
      use of long-acting reversible contraception, physicians may encounter difficult
      insertions and removals of intrauterine devices (IUDs) and the contraceptive
      implant. Uterine structure (e.g., extreme anteversion or retroversion, uterine
      tone during the postpartum period and breastfeeding) can pose challenges during
      IUD insertion. Special consideration is also needed for IUD insertions in
      patients who are transgender or gender nonconforming, such as psychosocial
      support and management of vaginal atrophy. Missing IUD strings may complicate
      removal, possibly requiring ultrasonography and use of instruments such as thread
      retrievers, IUD hooks, and alligator forceps. Regarding implant removal, those
      that are barely palpable (e.g., because of an overly deep insertion or excessive
      patient weight gain), removal may require ultrasonography, use of vas clamps and
      skin hooks, and extra dissection.

PMID- 30216024
TI  - Chewing Gum for Reducing Post-Cesarean Section Ileus.

PMID- 30216023
TI  - Blood Pressure Targets for Patients with Hypertension and Cardiovascular Disease.

PMID- 30216021
TI  - Annular Lesions: Diagnosis and Treatment.
AB  - Annular lesions can present in a variety of diseases. Knowledge of the physical
      appearance and history of presentation of these skin findings can help in the
      diagnosis. A pruritic, annular, erythematous patch that grows centrifugally
      should prompt evaluation for tinea corporis. Tinea corporis may be diagnosed
      through potassium hydroxide examination of scrapings. Recognizing erythema
      migrans is important in making the diagnosis of Lyme disease so that antibiotics
      can be initiated promptly. Plaque psoriasis generally presents with sharply
      demarcated, erythematous silver plaques. Erythema multiforme, which is due to a
      hypersensitivity reaction, presents with annular, raised lesions with central
      clearing. Lichen planus characteristically appears as planar, purple, polygonal,
      pruritic papules and plaques. Nummular eczema presents as a rash composed of coin
      shaped papulovesicular erythematous lesions. Treatment is aimed at reducing skin
      dryness. Pityriasis rosea presents with multiple erythematous lesions with
      raised, scaly borders, and is generally self-limited. Urticaria results from the
      release of histamines and appears as well-circumscribed, erythematous lesions
      with raised borders and blanched centers. Annular lesions occur less commonly in
      persons with fixed drug eruptions, leprosy, immunoglobulin A vasculitis,
      secondary syphilis, sarcoidosis, subacute cutaneous lupus erythematosus, and
      granuloma annulare.

PMID- 30216025
TI  - Common Foot Problems: Over-the-Counter Treatments and Home Care.
AB  - Most foot disorders do not require podiatry referral or complex interventions.
      After the clinical diagnosis is made, these conditions can typically be managed
      with over-the-counter (OTC) and home remedies, with guidance from the primary
      care physician. Stretching and strengthening exercises, along with the use of
      heel cups, resolve most plantar fasciitis cases and are at least as effective as
      nonsteroidal anti-inflammatory drugs or steroid injections. Hallux rigidus is
      best managed with a hard-soled shoe or rigid insert that relieves pain by
      restricting motion across the metatarsophalangeal joint. Hallux valgus responds
      to use of wide toe box shoes, and surgery is not clearly beneficial beyond one
      year. Plantar warts can be treated effectively at home with OTC salicylic acid
      and cryotherapy topical agents, which have equal effectiveness to liquid
      nitrogen. In patients with corns and calluses, OTC topical salicylic acid has
      short-term benefits, and pads and inserts that more evenly redistribute contact
      forces have long-term benefits. Inserts are commonly recommended to redistribute
      forefoot pressure and relieve pain. Several OTC preparations are available for
      the treatment of tinea pedis, with topical allylamines being the most effective.
      Although OTC topical treatments have been widely used for onychomycosis, they
      have poor long-term cure rates compared with prescription oral medications.

PMID- 30216035
TI  - Common Foot Problems: Home Treatments.

PMID- 30216032
TI  - A Painless Facial Nodule.

PMID- 30216033
TI  - Radon: A Leading Environmental Cause of Lung Cancer.

PMID- 30216034
TI  - Case Report: Successful Maternal and Fetal Outcomes After Uterine Rupture.

PMID- 30216028
TI  - Management of Insomnia Disorder in Adults.

PMID- 30216036
TI  - Light Extraction Enhancement in Flexible Organic Light-Emitting Diodes by a Light
      Scattering Layer of Dewetted Ag Nanoparticles at Low Temperatures.
AB  - We demonstrated light extraction improvement by applying a scattering layer of Ag
      nanoparticles physically synthesized through a low-temperature annealing process
      to flexible organic light-emitting diodes (OLEDs). In general, increasing the
      size of Ag nanoparticles is preferred to increase light scattering, but a high
      temperature annealing process (~400  degrees C) is required to produce them.
      However, flexible substrates generally cannot withstand high-temperature
      processes. In this study, we formed Ag nanoparticles at a low temperature of ~200
      degrees C by inserting a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate
      buffer layer, thus promoting Ag dewetting. As a result, the scattering layer of
      enlarged Ag nanoparticles formed at low temperatures increased the external
      quantum efficiency by 24% in a flexible OLED compared to a reference device.

PMID- 30216039
TI  - DARK Classics in Chemical Neuroscience: Ibogaine.
AB  - The West African iboga plant has been used for centuries by the Bwiti and Mbiri
      tribes to induce hallucinations during religious ceremonies. Ibogaine, the
      principal alkaloid responsible for iboga's psychedelic properties, was isolated
      and sold as an antidepressant in France for decades before its adverse effects
      precipitated its removal from the market. An ibogaine resurgence in the 1960s was
      driven by U.S. heroin addicts who claimed that ibogaine cured their opiate
      addictions. Behavioral pharmacologic studies in animal models provided evidence
      that ibogaine could blunt self-administration of not only opiates but cocaine,
      amphetamines, and nicotine. Ibogaine displays moderate-to-weak affinities for a
      wide spectrum of receptor and transporter proteins; recent work suggests that its
      actions at nicotinic acetylcholine receptor subtypes may underlie its reputed
      antiopiate effects. At micromolar levels, ibogaine is neurotoxic and cardiotoxic
      and has been linked to several deaths by cardiac arrest. Structure-activity
      studies led to the isolation of the ibogaine analog 18-methoxycoronaridine (18
      MC), an alpha3beta4 nicotinic receptor modulator that retains ibogaine's
      anticraving properties with few or no adverse effects. Clinical trials of 18-MC
      treatment of nicotine addiction are pending. Ibogaine analogs may also hold
      promise for treating anxiety and depression via the "psychedelic-assisted
      therapy" approach that employs hallucinogens including psilocybin and
      methylenedioxymethamphetamine ("ecstasy").

PMID- 30216037
TI  - Novel Alkaline Zn/Na0.44MnO2 Dual-Ion Battery with a High Capacity and Long Cycle
      Lifespan.
AB  - A rechargeable aqueous Zn/Mn battery is a promising device for large-scale energy
      storage because of its abundant resources, low cost, and high safety. However,
      its application is plagued by a poor life cycle because of the electrochemical
      instability of MnO2 in aqueous electrolytes. Here, an alkaline Zn-Na0.44MnO2 dual
      ion battery (denoted AZMDIB) is developed for the first time using Na0.44MnO2 as
      the cathode, a zinc metal sheet as the anode, and a 6 M NaOH aqueous solution as
      the electrolyte. When the discharge cutoff voltage is lowered to 0.3 V (vs
      Zn/Zn2+), the Na0.44MnO2 cathode delivers a high capacity of 345.5 mA h g-1 but
      with a poor cycling performance. The charge-discharge mechanism and structural
      evolution of the Na0.44MnO2 cathode in an extended potential window (1.95-0.3 V)
      are also explored. The Na0.44MnO2 electrode experiences two different
      electrochemical processes: Na+ ions insert/extract reversibly in the potential
      range of 1.95-1.1 V, and a phase transition occurs from Na0.559MnO2 to Mn(OH)2
      below 1.1 V. The latter irreversible reaction is probably due to proton
      insertion, leading to a severe capacity fade. Nevertheless, in a narrower voltage
      range (2.0-1.1 V), the AZMDIB full cell exhibits a high reversible capacity (80.2
      mA h g-1 at 0.5 C), high rate capability (32 mA h g-1 at 50 C), and excellent
      cycling stability (73% capacity retention over 1000 cycles at 10 C). Benefiting
      from the merits of environmental friendliness, cost-effectiveness, and high
      electrochemical performance, the rechargeable AZMDIB is a promising contender for
      grid-scale energy storage applications.

PMID- 30216026
TI  - Feed Thickener for Newborn Infants with Gastroesophageal Reflux.

PMID- 30216043
TI  - Computationally Guided Identification of Allosteric Agonists of the Metabotropic
      Glutamate 7 Receptor.
AB  - The metabotropic glutamate 7 (mGlu7) receptor belongs to the group III of mGlu
      receptors. Since the mGlu7 receptor can control excitatory neurotransmission in
      the hippocampus and cortex, modulation of the receptor may have therapeutic
      benefit in several CNS diseases. However, mGlu7 remains relatively unexplored
      among the eight known mGlu receptors partly because of the limited availability
      of tool compounds to interrogate its potential therapeutic utility. Here we
      report the discovery of a new class of mGlu7 allosteric agonists. Hits
      originating from virtual screening were followed up with further analogue
      searching and screening, leading to a novel series of mGlu7 allosteric agonists.
      Guided by docking into a structural model of the mGlu7 receptor the initial hit 5
      was successfully optimized to analogues with comparable potencies and more
      attractive drug-like attributes than AMN082.

PMID- 30216038
TI  - Anisotropy-Driven High Thermal Conductivity in Stretchable Poly(vinyl
      alcohol)/Hexagonal Boron Nitride Nanohybrid Films.
AB  - Controlling the anisotropy of two-dimensional materials with orientation
      dependent heat transfer characteristics is a possible solution to resolve severe
      thermal issues in future electronic devices. We demonstrate a dramatic
      enhancement in the in-plane thermal conductivity of stretchable poly(vinyl
      alcohol) (PVA) nanohybrid films containing small amounts (below 10 wt %) of
      hexagonal boron nitride ( h-BN) nanoplatelets. The h-BN nanoplatelets were
      homogeneously dispersed in the PVA polymer solution by ultrasonication without
      additional surface modification. The mixture was used to prepare thermally
      conductive nanocomposite films. The in-plane thermal conductivity of the
      resulting PVA/ h-BN nanocomposite films increased to 6.4 W/mK when the strain was
      increased from 0 to 100% in the horizontal direction. More specifically, the
      thermal conductivity of a PVA/ h-BN composite film with 10 wt % filler loading
      can be improved by up to 32 times as compared to pristine PVA. This outstanding
      thermal conductivity value is significantly larger than that of materials
      currently used in in-plane thermal management systems. This result is attributed
      to the anisotropic alignment of h-BN particles in the PVA chain matrix during
      stretching, enhancing phonon conductive paths and hence improving the thermal
      conductivity and thermal properties of PVA/ h-BN nanocomposite films. These
      polymer nanocomposites have low cost as the amount of expensive conductive
      fillers is reduced and can be potentially used as high-performance materials for
      thermal management systems such as heat sink and thermal interface materials, for
      future electronic and electrical devices.

PMID- 30216040
TI  - Tuning Transition-Metal Dichalcogenide Field-Effect Transistors by Spontaneous
      Pattern Formation of an Ultrathin Molecular Dopant Film.
AB  - Spontaneous pattern formation is an energetically favorable process and is shown
      in nature in molecular-scale assembly, biological association, and soft material
      organizations. The opposite regime, the artificial process, which is widely
      applied to the fabrication of semiconducting devices, such as lithographic
      techniques, requires enormous amounts of energy. Here, we propose a concept of
      tuning the properties of semiconducting MoS2 and WSe2 devices using the
      spontaneous pattern formation of adjacent molecular films. The film used was a 10
      nm thick ultrathin film of a molecular electron dopant, which exhibited
      spontaneous pattern formation and dynamically transformed the morphology of tiny
      holes, a network, a maze, and dots on substrates, including SiO2, MoS2, and WSe2.
      These patterns were exhibited only when the film came in contact with water and
      was tuned with temperature and time. The specific lengths of the patterns were
      less than 200 nm, which is sufficiently smaller than the exfoliated ~10 MUm
      semiconducting MoS2 and WSe2 flakes. The properties of the field-effect devices
      of MoS2 and WSe2 were found to be modified according to the pattern formation
      process of the ultrathin molecular film on the device. This concept applies the
      spontaneous patterning phenomena shown in nature to the fabrication and
      optimization of electronic devices by using molecular films and their responses
      to the external environment.

PMID- 30216045
TI  - Enhanced Multiple Exciton Generation in PbS|CdS Janus-like Heterostructured
      Nanocrystals.
AB  - Generating multiple excitons by a single high-energy photon is a promising third
      generation solar energy conversion strategy. We demonstrate that multiple exciton
      generation (MEG) in PbS|CdS Janus-like heteronanostructures is enhanced over that
      of single-component and core/shell nanocrystal architectures, with an onset close
      to two times the PbS band gap. We attribute the enhanced MEG to the asymmetric
      nature of the heteronanostructure that results in an increase in the effective
      Coulomb interaction that drives MEG and a reduction of the competing hot exciton
      cooling rate. Slowed cooling occurs through effective trapping of hot-holes by a
      manifold of valence band interfacial states having both PbS and CdS character, as
      evidenced by photoluminescence studies and ab initio calculations. Using
      transient photocurrent spectroscopy, we find that the MEG characteristics of the
      individual nanostructures are maintained in conductive arrays and demonstrate
      that these quasi-spherical PbS|CdS nanocrystals can be incorporated as the main
      absorber layer in functional solid-state solar cell architectures. Finally, based
      upon our analysis, we provide design rules for the next generation of engineered
      nanocrystals to further improve the MEG characteristics.

PMID- 30216046
TI  - Portable Infrared Isothermal PCR Platform for Multiple Sexually Transmitted
      Diseases Strand Detection.
AB  - Rapid and portable PCR detection is essential for screening sexually transmitted
      infections regularly. We developed an infrared mediated RNA isothermal RT-PCR (IR
      MERIT PCR) platform and its compatible multichamber microfluidic chip for
      simultaneous amplification and testing (SAT) detection. This microfluidic chip
      integrates RNA extraction, micropump, and multitarget detection function onto the
      same chip. By utilizing IR-light-emitting diode (LED) as heat source, this
      platform can fulfill isothermal amplification within 70 min.

PMID- 30216044
TI  - Ladderlike Tapered Pillars Enabling Spontaneous and Consecutive Liquid Transport.
AB  - Directional liquid transport has significant domestic and industrial
      applications. Tapered objects have theoretically and experimentally been
      demonstrated to have the ability to spontaneously transport liquids. However, the
      transporting distance is limited, and consecutively and spontaneously
      transporting liquids has always been a challenge. In this work we proposed to
      exploit ladderlike tapered pillars, which are inspired by relay races, to
      increase the transport distance. These pillars were designed using a developed
      numerical model and fabricated by a novel alternating etching and coating method
      followed by wettability enhancement. We demonstrated through experiments that the
      resulting pillars could consecutively and spontaneously transport a liquid
      droplet at an average velocity of 0.139 m/s with a maximum acceleration of 5 g.
      The optimum window of the tilt angle range (0 degrees -25 degrees ), contact
      angle (50 degrees ), and the chemical modification time (5 min) were obtained.
      Such ladderlike tapered pillars are able to improve the water-collection
      efficiency. These results may provide a new and systematic way to design and
      fabricate materials and structures for directional liquid transport.

PMID- 30216041
TI  - Systematic Evaluation of Soluble Protein Expression Using a Fluorescent Unnatural
      Amino Acid Reveals No Reliable Predictors of Tolerability.
AB  - Improvements in genetic code expansion have made preparing proteins with diverse
      functional groups almost routine. Nonetheless, unnatural amino acids (Uaas) pose
      theoretical burdens on protein solubility, and determinants of position-specific
      tolerability to Uaas remain underexplored. To broadly examine associations, we
      systematically assessed the effect of substituting the fluorescent Uaa,
      acridonylalanine, at more than 50 chemically, evolutionarily, and structurally
      diverse residues in two bacterial proteins: LexA and RecA. Surprisingly,
      properties that ostensibly contribute to Uaa tolerability-such as conservation,
      hydrophobicity, or accessibility-demonstrated no consistent correlations with
      resulting protein solubility. Instead, solubility is closely dependent on the
      location of the substitution within the overall tertiary structure, suggesting
      that intrinsic properties of protein domains, and not individual positions, are
      stronger determinants of Uaa tolerability. Consequently, those who seek to
      install Uaas in new target proteins should consider broadening, rather than
      narrowing, the types of residues screened for Uaa incorporation.

PMID- 30216047
TI  - Dissection of Fragmentation Pathways in Protonated N-Acetylhexosamines.
AB  - Structural characterization of carbohydrates by mass spectrometry necessitates a
      detailed understanding of their gas phase behavior, particularly for protonated
      carbohydrates that can undergo complex structural rearrangements during
      fragmentation. Here we utilize tandem mass spectrometry, isotopic labeling, gas
      phase hydrogen/deuterium exchange, and ion mobility measurements to characterize
      structures of the various product ions of protonated N-acetylhexosamines.
      Following the facile loss of the reducing end hydroxyl group, we identify two
      primary fragmentation pathways. Detailed mapping of each step in the
      fragmentation pathway provides new insight into the mechanisms that drive
      collision-induced dissociation of protonated carbohydrates. Several of the
      smaller fragment ions are mixtures of structural isomers, and the relative
      distributions of these structures reveals information about the stereochemistry
      of the precursor molecule.

PMID- 30216048
TI  - Assessment of Radiation Resistance and Therapeutic Targeting of Cancer Stem
      Cells: A Raman Spectroscopic Study of Glioblastoma.
AB  - Radiation is the standard therapy used for treating Glioblastoma (GBM), a grade
      IV brain cancer. Glioma Stem-like Cells (GSCs), an integral part of GBM, enforces
      resistance to radiation therapy of GBM. Studying the differential biomolecular
      composition of GSCs with varying levels of radiation sensitivity can aid in
      identifying the molecules and their associated pathways which impose resistance
      to cells thereby unraveling new targets which would serve as potential adjuvant
      therapy. Raman spectroscopy being a noninvasive, label free technique can
      determine the biomolecular constituent of cells under live conditions. In this
      study, we have deduced Raman spectral signatures to predict the radiosensitivity
      of any GSC accurately using the inherent and radiation induced biomolecular
      composition. Our study identified the differential regulation of several
      biomolecules which can be potential targets for adjuvant therapy. We
      radiosensitized the resistant GSCs using small molecule inhibitors specific to
      the metabolic pathways of these biomolecules. Efficient antitumor therapy can be
      attained with lower dosage of radiation along with these inhibitors and thus
      improving the survival rate of GBM patients with reduced side-effects from
      radiation.

PMID- 30216050
TI  - Evaluating the Use of Silicone Wristbands To Measure Personal Exposure to
      Brominated Flame Retardants.
AB  - Biomarkers remain the gold standard for assessing chemical exposure. However,
      silicone wristbands may provide some added benefits for characterizing personal
      exposures compared to single biomarker measurements, such as decreased costs,
      noninvasive sampling, and increased ease of analysis. Previously, we validated
      their use in characterizing exposure to organophosphate flame retardants (PFRs).
      However, it is unclear whether these results would extend to chemicals like
      polybrominated diphenyl ethers (PBDEs), which biomagnify and have longer half
      lives than PFRs in the body. This study sought to determine if accumulation of
      PBDEs on wristbands was correlated to serum biomarkers. Adult participants ( n =
      30) provided serum samples and wore wristbands for 7 days. PBDEs and 6 novel
      brominated flame retardants (BFRs) were measured on wristbands, and serum samples
      were analyzed for PBDE biomarkers. Like most PBDE congeners, 5 of 6 novel BFRs
      were frequently detected on wristbands (>=90% of bands). In particular,
      decabromodiphenyl ethane (DBDPE) was detected in all wristbands in this study and
      was significantly correlated with BDE-209, suggesting a similar source and
      exposure pathway. Wristband levels of BDE-47, -99, -100, and -153 were
      significantly and positively associated with respective serum biomarkers ( rs =
      0.39-0.57, p < 0.05). This study demonstrates that silicone wristbands can
      accurately detect personal PBDE exposures.

PMID- 30216042
TI  - Chemical Instability and Promiscuity of Arylmethylidenepyrazolinone-Based MDMX
      Inhibitors.
AB  - Targeting the protein-protein interaction between p53 and MDM2/MDMX (MDM4)
      represents an attractive anticancer strategy for the treatment of p53-competent
      tumors. Several selective and potent MDM2 inhibitors have been developed and
      entered the clinic; however, the repertoire of MDMX antagonists is still limited.
      The arylmethylidenepyrazolinone SJ-172550 has been reported as a selective MDMX
      antagonist; yet, uncertainties about its mechanism of action have raised doubts
      about its use as a chemical probe. Here, we show that, in addition to its unclear
      mode of action, SJ-172550 is unstable in aqueous buffers, giving rise to side
      products of unknown biological activity. Using an SJ-172550-derived affinity
      probe, we observed promiscuous binding to cellular proteins whereas cellular
      thermal shift assays did not reveal a stabilizing effect on MDMX. Overall, our
      results raise further questions about the interpretation of data using SJ-172550
      and related compounds to investigate cellular phenotypes.

PMID- 30216051
TI  - Cloning and Expression of a Nonribosomal Peptide Synthetase to Generate Blue
      Rose.
AB  - Rose has been entwined with human culture and history. "Blue rose" in English
      signifies unattainable hope or an impossible mission as it does not exist
      naturally and is not breedable regardless of centuries of effort by gardeners.
      With the knowledge of genes and enzymes involved in flower pigmentation and
      modern genetic technologies, synthetic biologists have undertaken the challenge
      of producing blue rose by engineering the complicated vacuolar flavonoid
      pigmentation pathway and resulted in a mauve-colored rose. A completely different
      strategy presented in this study employs a dual expression plasmid containing
      bacterial idgS and sfp genes. The holo-IdgS, activated by Sfp from its apo-form,
      is a functional nonribosomal peptide synthetase that converts l-glutamine into
      the blue pigment indigoidine. Expression of these genes upon petal injection with
      agro-infiltration solution generates blue-hued rose flowers. We envision that
      implementing this proof-of-concept with obligatory modifications may have
      tremendous impact in floriculture to achieve a historic milestone in rose
      breeding.

PMID- 30216049
TI  - Productive Amyrin Synthases for Efficient alpha-Amyrin Synthesis in Engineered
      Saccharomyces cerevisiae.
AB  - alpha-Amyrin is a plant-derived pentacyclic triterpenoid, with a lot of important
      physiological and pharmacological activities. The formation of alpha-amyrin from
      (3 S)-2,3-oxidosqualene is catalyzed by alpha-amyrin synthase (alpha-AS), a
      member of the oxidosqualene cyclase (OSC) protein family. However, alpha-amyrin
      is not yet commercially developed due to its extremely low productivity in
      plants. The engineered Saccharomyces cerevisiae with efficient alpha-amyrin
      production pathway could be used as an alternative and sustainable solution to
      produce alpha-amyrin from renewable raw materials. To efficiently improve alpha
      amyrin production in S. cerevisiae, we identified two alpha-ASs, EjAS and MdOSC1
      from Eriobotrya japonica and Malus * domestica, respectively, through strict
      bioinformatics screening criteria and phylogenetic analysis. The specific
      activities of purified EjAS and MdOSC1 were 0.0032 and 0.0293 MUmol/min/mg,
      respectively. EjAS produced alpha-amyrin and beta-amyrin at a ratio of 17:3,
      MdOSC1 produced alpha-amyrin, beta-amyrin and lupeol at a ratio of 86:13:1,
      indicating MdOSC1 had significantly higher specific activity and higher ratio of
      alpha-amyrin than EjAS. Furthermore, MdOSC1 was introduced into S. cerevisiae
      combining with the increased supply of (3 S)-2,3-oxidosqualene to achieve the
      encouraging alpha-amyrin production, and the titer of alpha-amyrin achieved 11.97
      +/- 0.61 mg/L, 5.8 folds of the maximum production reported.

PMID- 30216052
TI  - Deciphering the Microstructure and Energy-Level Splitting of Tm3+-Doped Yttrium
      Aluminum Garnet.
AB  - Thulium-doped yttrium aluminum garnet (Tm:YAG) is an important solid-state laser
      crystal. The energy-level splitting within it is still an unresolved problem.
      Here, we perform a theoretical study on the microstructure of Tm3+-doped YAG
      using the CALYPSO structure search method in conjunction with first-principles
      calculations. The calculated results show that the 4.16% doping concentration of
      Tm3+ impurity causes an obvious structural distortion of YAG crystal, forming an
      orthorhombic phase in C222 symmetry. On the basis of our developed WEPMD method,
      we obtain a new and complete set of free-ion and crystal field parameters by a
      good fit (with proper irreducible representations) to 69 observed energy levels
      and determine the exact energy-level splitting of Tm3+ in YAG. The calculated
      Stark levels and electric dipole transitions are in excellent agreement with the
      measured data and similar theoretical calculations. Some promising emission lines
      between 3F3, 3F2, 1D2, and 1I6 states are presented. These findings offer
      fundamental insights and practical tools for further exploration of the
      structural and electronic properties of other transition-metal-doped YAG crystal.

PMID- 30216053
TI  - Catalytic Cyclooligomerization of Enones with Three Methylene Equivalents.
AB  - Cyclic structures are highly represented in organic molecules, motivating a
      wealth of catalytic methods targeting their synthesis. Among the various ring
      forming processes, cyclooligomerization reactions possess several attractive
      features but require addressing a unique challenge associated with controlling
      ring-size selectivity. Here we describe the catalytic reductive
      cocyclooligomerization of an enone and three carbene equivalents to generate a
      cyclopentane, a process that constitutes a formal [2 + 1 + 1 + 1]-cycloaddition.
      The reaction is promoted by a (quinox)Ni catalyst and uses CH2Cl2/Zn as the C1
      component. Mechanistic studies are consistent with a metallacycle-based pathway,
      featuring sequential migratory insertions of multiple carbene equivalents to
      yield cycloalkanes larger than cyclopropanes.

PMID- 30216055
TI  - Guide to Selecting a Biorecognition Element for Biosensors.
AB  - Biosensors are powerful diagnostic tools defined as having a biorecognition
      element for analyte specificity and a transducer for a quantifiable signal. There
      are a variety of different biorecognition elements, each with unique
      characteristics. Understanding the advantages and disadvantages of each
      biorecognition element and their influence on overall biosensor performance is
      crucial in the planning stages to promote the success of novel biosensor
      development. Therefore, this review will focus on selecting the optimal
      biorecognition element in the preliminary design phase for novel biosensors.
      Included is a review of the typical characteristics and binding mechanisms of
      various biorecognition elements, and how they relate to biosensor performance
      characteristics, specifically sensitivity, selectivity, reproducibility, and
      reusability. The goal is to point toward language needed to improve the design
      and development of biosensors toward clinical success.

PMID- 30216054
TI  - Streamlined Total Synthesis of Shishijimicin A and Its Application to the Design,
      Synthesis, and Biological Evaluation of Analogues thereof and Practical Syntheses
      of PhthNSSMe and Related Sulfenylating Reagents.
AB  - Shishijimicin A is a scarce marine natural product with highly potent
      cytotoxicities, making it a potential payload or a lead compound for designed
      antibody-drug conjugates. Herein, we describe an improved total synthesis of
      shishijimicin A and the design, synthesis, and biological evaluation of a series
      of analogues. Equipped with appropriate functionalities for linker attachment, a
      number of these analogues exhibited extremely potent cytotoxicities for the
      intended purposes. The synthetic strategies and tactics developed and employed in
      these studies included improved preparation of previously known and new
      sulfenylating reagents such as PhthNSSMe and related compounds.

PMID- 30216056
TI  - Very Long-Lived Photogenerated High-Spin Phase of a Multistable Spin-Crossover
      Molecular Material.
AB  - The spin-crossover compound [Fe( n-Bu-im)3(tren)](PF6)2 shows an unusual long
      relaxation time of 20 h after light-induced excited spin state trapping when
      irradiating at 80 K. This is more than 40 times longer than when irradiating at
      10 K. Optical absorption spectroscopy, magnetometry, and X-ray diffraction using
      synchrotron radiation were used to characterize and explain the different
      relaxation behaviors of this compound after irradiation below and above 70 K.
      Rearrangement of the butyl chains of the ligands occurring during the relaxation
      after irradiation above 70 K is thought to be responsible for the unusually long
      relaxation time at this temperature.

PMID- 30216057
TI  - Correction to "Generality and Strength of Transition Metal beta-Effects".

PMID- 30216058
TI  - In Situ and ex Situ Study of Cubic La0.5Ba0.5CoO3-delta to Double Perovskite
      LaBaCo2O6-delta Transition and Formation of Domain Textured Phases with Fast
      Oxygen Exchange Capability.
AB  - The disordered La0.5Ba0.5CoO3-delta <-> ordered LaBaCo2O6-delta transition was
      studied in detail using several complementary in situ (X-ray diffraction,
      thermogravimetry, and coulometric titration) and ex situ (transmission electron
      microscopy) techniques. This transition was found to proceed through the
      formation of complex domain textured intermediate products. They were shown to
      have strong affinity to oxygen and exhibit its fast absorption from ambient
      atmosphere (oxygen partial pressure ( pO2) 0.21 atm) at a temperature as low as
      70  degrees C. The thermodynamic stability limits of the cubic and double
      perovskites were determined by coulometric titration. The stability diagram of
      the LaBaCo2O6-delta - La0.5Ba0.5CoO3-delta system was plotted as a result. Oxygen
      nonstoichiometry of the thermodynamically stable cubic perovskite La0.5Ba0.5CoO3
      delta was measured as a function of pO2 in the temperature range between 1000 and
      1100  degrees C using a coulometric titration technique.

PMID- 30216059
TI  - Diastereoselective Allylation of Aldehydes by Dual Photoredox and Chromium
      Catalysis.
AB  - Herein, we report the redox-neutral allylation of aldehydes with readily
      available electron-rich allyl (hetero-) arenes, beta-alkyl styrenes and allyl
      diarylamines. This process was enabled by the combination of photoredox and
      chromium catalysis, which allowed a range of homoallylic alcohols to be prepared
      with high levels of selectivity for the anti diastereomer. Mechanistic
      investigations support the formation of an allyl chromium intermediate from
      allylic C(sp3)-H bonds and thus significantly extends the scope of the venerable
      Nozaki-Hiyama-Kishi reaction.

PMID- 30216060
TI  - Cytochrome P450-Catalyzed Hydroxylation Initiating Ether Formation in
      Platensimycin Biosynthesis.
AB  - Platensimycin (PTM) and platencin (PTN) are potent and selective inhibitors of
      bacterial and mammalian fatty acid synthases. The regio- and stereospecificity of
      the ether oxygen atom in PTM, which PTN does not have, strongly contribute to the
      selectivity and potency of PTM. We previously reported the biosynthetic origin of
      the 11 S,16 S-ether moiety by characterizing the diterpene synthase PtmT3 as a
      (16 R)- ent-kauran-16-ol synthase and isolating 11-deoxy-16 R-hydroxylated
      congeners of PTM from the Delta ptmO5 mutant. PtmO5, a cytochrome P450, was
      proposed to catalyze formation of the ether moiety in PTM. Here we report the in
      vitro characterization of PtmO5, revealing that PtmO5 stereoselectively
      hydroxylates the C-11 position of the ent-kaurane scaffold resulting in an 11
      S,16 R-diol intermediate. The ether moiety, the oxygen of which originates from
      the P450-catalyzed hydroxylation at C-11, is formed via cyclization of the diol
      intermediate. This study provides mechanistic insight into ether formation in
      natural product biosynthetic pathways.

PMID- 30216063
TI  - Targeting Cytochrome P450 (CYP) 1B1 Enzyme with Four Series of A-Ring Substituted
      Estrane Derivatives: Design, Synthesis, Inhibitory Activity, and Selectivity.
AB  - Cytochrome P450 (CYP) 1B1 is involved in the bioactivation of procarcinogens and
      drug resistance. To obtain selective CYP1B1 inhibitors over CYP1A1, we
      synthesized four series of estrane derivatives: (1) 12 estrone (E1)- and 17beta
      estradiol (E2)-derivatives bearing a 3- or a 4-pyridinyl core at C2, C3, or C4,
      (2) eight estrane derivatives with different sulfur groups at C3, (3) 19 E1- and
      E2-derivatives bearing distinct aryls at C2, and (4) five D-ring derivatives. E2
      derivatives were more active than oxidized E1-analogues, thus highlighting the
      key role of 17beta-OH for interaction with CYP1B1. 2-(4-Fluorophenyl)-E2 was the
      best CYP1B1 inhibitor (IC50 = 0.24 MUM), with a selectivity index (SI) of 20 over
      CYP1A1. Furthermore, the addition of a C17alpha-ethynyl group as D-ring
      modification improved the selectivity index to 25 with only a slight loss of
      activity (IC50 = 0.37 MUM). Our docking results showed that these compounds fit
      better into the CYP1B1 binding site than that of CYP1A1.

PMID- 30216062
TI  - Potential Functional Embedding Theory with an Improved Kohn-Sham Inversion
      Algorithm.
AB  - Potential functional embedding theory (PFET) is a rigorous theory that can yield
      a unique, self-consistent embedding potential shared by different subsystems
      treated at different levels of theory. Application of PFET has been limited by
      the time-consuming and sometimes unstable optimized effective potential (OEP)
      procedure. Here, we improve the performance of PFET by replacing the OEP
      algorithm with a new method to reconstruct the effective Kohn-Sham (KS)
      potential. We propose a direct, efficient KS inversion algorithm to solve for the
      effective KS potential and then employ the resulting algorithm in PFET. We
      benchmark our KS inversion algorithm against the recently reported modified
      Ryabinkin-Kohut-Staroverov (mRKS) procedure. Numerical examples show that, with
      sufficiently large basis sets, our KS inversion algorithm generates almost as
      accurate results as the mRKS procedure does, except in the vicinity of atomic
      nuclei, and that it requires less computational time. Three types of chemical
      interactions then were tested using the new KS inversion algorithm in PFET; the
      energetics computed from the updated formalism compare well to benchmarks.

PMID- 30216061
TI  - Combining (Non)linear Optical and Fluorescence Analysis of DiD To Enhance Lipid
      Phase Recognition.
AB  - The widespread interest in phase recognition of lipid membranes has led to the
      use of different optical techniques to enable differentiation of healthy and not
      fully functional cells. In this work, we show how the combination of different
      (non)linear optical methods such as one-photon absorption (OPA), two-photon
      absorption (TPA), and second harmonic generation (SHG) as well as the study of
      the fluorescence decay time leads to an enhanced screening of membrane phases
      using a fluorescent 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiD)
      probe. In the current study we consider the pure liquid disordered phases of DOPC
      (dioleoyl- sn-glycero-3-phosphocholine, room temperature) and DPPC (1,2
      dipalmitoyl- sn-glycero-3-phosphocholine, 323 K), the solid gel phase of DPPC
      (298 K), and the liquid ordered phase of a 2:1 binary mixture of sphingomyelin
      and cholesterol. By means of extensive hybrid quantum mechanics-molecular
      mechanics calculations and based upon the (non)linear absorption of the embedded
      probes, it is found that DiD can be used to identify the lipid bilayer phase. The
      joint TPA and SHG as well as fluorescence analyses qualifies DiD as a versatile
      probe for phase recognition. In particular, the SHG data obtained by means of
      hyper-Rayleigh scattering and by electric field induced second harmonic
      generation reveal differences in polarization of the probe in the different
      environments. The TPA results finally confirm the particular location of the
      probe in between the polar headgroup region of the 2:1 SM:Chol mixture in the
      liquid ordered phase.

PMID- 30216064
TI  - Phorbol Rearrangements.
AB  - An alternative procedure for isolation of 4beta-phorbol from seeds of Croton
      tiglium has been developed, and an artifact containing a furan ring formed by
      rearrangement of 12,13,20- O-triacylated phorbol derivatives into (6b S,7 R,8
      R,8a S)-2-(hydroxymethyl)-5,7,9,9-tetramethyl-3,7,8,9,9a,9b
      hexahydrocyclopropa[3',4']benzo[1',2':3,4]cyclohepta[1,2- b]furan-6b,8,8a-triol
      (8a) has been characterized. A mechanism involving an oxidative rearrangement and
      a decarboxylation for formation of the artifact is proposed.

PMID- 30216065
TI  - Total Synthesis of (+)-Pyrenolide D.
AB  - An efficient approach to stereoselective construction of a spiro-gamma-lactone
      core structure via BF3-promoted formal [3 + 2] annulation of aldehydo-aldose
      derivatives with gamma-methylene-gamma-butyrolactone has been developed. The
      spiro-gamma-lactone derivative was then used in an efficient total synthesis of
      (+)-pyrenolide D. The developed chemistry paves the way for total synthesis of
      structurally diverse natural products containing spiro-lactone cores.

PMID- 30216066
TI  - Total Synthesis of Notoryne.
AB  - The structure of notoryne comprises a halogenated 2,2'-bifuranyl moiety along
      with a terminal cis-enyne unit. In this work, we document the first total
      synthesis of notoryne, confirming its assigned relative and absolute
      configurations. The devised route comprises a glucose diacetonide-derived chiral
      pool intermediate as the starting point and 5- endo bromo-etherification for
      making the key bis-furan unit, anomeric C-allylation, as well as a relay cross
      metathesis to install the cis-enyne unit.

PMID- 30216067
TI  - Kirkwood-Buff-Derived Alcohol Parameters for Aqueous Carbohydrates and Their
      Application to Preferential Interaction Coefficient Calculations of Proteins.
AB  - The CHARMM36 carbohydrate parameter set did not adequately reproduce experimental
      thermodynamic data of carbohydrate interactions with water or proteins or
      carbohydrate self-association; thus, a new nonbonded parameter set for
      carbohydrates was developed. The parameters were developed to reproduce
      experimental Kirkwood-Buff integral values, defined by the Kirkwood-Buff theory
      of solutions, and applied to simulations of glycerol, sorbitol, glucose, sucrose,
      and trehalose. Compared to the CHARMM36 carbohydrate parameters, these new
      Kirkwood-Buff-based parameters reproduced accurately carbohydrate self
      association and the trend of activity coefficient derivative changes with
      concentration. When using these parameters, preferential interaction coefficients
      calculated from simulations of these carbohydrates and the proteins lysozyme,
      bovine serum albumin, alpha-chymotrypsinogen A, and RNase A agreed well with the
      experimental data, whereas use of the CHARMM36 parameters indicated preferential
      inclusion of carbohydrates, in disagreement with the experiment. Thus,
      calculating preferential interaction coefficients from simulations requires using
      a force field that accurately reproduces trends in the thermodynamic properties
      of binary excipient-water solutions, and in particular the trend in the activity
      coefficient derivative. Finally, the carbohydrate-protein simulations using the
      new parameters indicated that the carbohydrate size was a major factor in the
      distribution of different carbohydrates around a protein surface.

PMID- 30216068
TI  - Regression Analysis for Nucleation-Elongation Model of Supramolecular Assembly:
      How To Determine Nucleus Size.
AB  - Nucleation-elongation is known to give satisfactory descriptions of many
      supramolecular polymerization systems in thermal equilibrium. Its key feature is
      the necessity to form a "nucleus" consisting of a certain number of monomer units
      before being able to grow into a longer polymer chain. The size of the nucleus
      has significant implications for the understanding of the supramolecular
      polymerization mechanism. Here we investigate how experiments can give
      information on the nucleus size by regression analysis of various types of
      measurements. The measurements of free monomer concentrations, diffusion
      coefficients, and calorimetric response as functions of concentration or
      temperature are considered. The nucleation-elongation model with a general value
      for the nucleus size is used to provide mathematical expressions for these
      experimental observables. Numerical experiments are performed where experimental
      errors are simulated by computer-generated random numbers, and it is investigated
      whether least-squares fitting analyses can give the correct values of the nucleus
      size in the presence of experimental errors. It is recommended that the
      calorimetric measurements such as differential scanning calorimetry (DSC) or
      isothermal titration calorimetry (ITC) be performed under various conditions to
      correctly determine the nucleus size experimentally.

PMID- 30216069
TI  - Insights into the Competition between K+ and Pb2+ Binding to a G-Quadruplex and
      Discovery of a Novel K+-Pb2+-Quadruplex Intermediate.
AB  - Numerous studies have reported cation-dependent stability and topological changes
      of G-quadruplexes (G4s), but competitions between cations at different
      concentrations for binding with G4s and their effects on the polymorphism of G4
      have been rarely investigated, which greatly limited the application of G4.
      Herein, with PW17 (a G4-forming DNA sequence) as a model system, the competition
      between K+ and Pb2+ for binding to G4 was clarified. Using a combination of
      circular dichroism and electrospray ionization mass spectroscopy, it was found
      that 10 MUM Pb2+ could replace K+ in K+-stabilized PW17 (2K+-PW17), but the
      substitution efficiency is highly dependent on K+ concentration (0.5-10 mM). In
      contrast, K+ at <10 mM could partly replace Pb2+ in stable and antiparallel Pb2+
      stabilized PW17 (Pb2+-PW17) and completely substitute Pb2+ at K+ >=10 mM. In
      these competing processes, a novel intermediate consisting of a Pb2+ and a K+ in
      the same G4 (K+-Pb2+-PW17) was first discovered, which acted as a bridge to
      achieve the switches. Through measuring the energetics of different
      concentrations of K+- and Pb2+-induced conformations, such a competitive binding
      was found to be thermodynamically permitted.

PMID- 30216070
TI  - A Copper-Mediated Conjugate Addition Approach to Analogues of Aconitine-Type
      Diterpenoid Alkaloids.
AB  - A copper-mediated conjugate addition of electron-rich aryl groups into a complex
      vinyl nitrile using arylmagnesium bromides is reported. The conjugate addition
      adducts were advanced toward the synthesis of designed aconitine-type analogues.
      The variation in oxygenation patterns on the arene coupling partner, introduced
      through the current conjugate addition approach, may ultimately provide insight
      into structure-activity relationships of the diterpenoid alkaloids.

PMID- 30216071
TI  - Analysis of Protein Complexes in the Unicellular Cyanobacterium Cyanothece ATCC
      51142.
AB  - The unicellular cyanobacterium Cyanothece ATCC 51142 is capable of oxygenic
      photosynthesis and biological N2 fixation (BNF), a process highly sensitive to
      oxygen. Previous work has focused on determining protein expression levels under
      different growth conditions. A major gap of our knowledge is an understanding on
      how these expressed proteins are assembled into complexes and organized into
      metabolic pathways, an area that has not been thoroughly investigated. Here, we
      combined size-exclusion chromatography (SEC) with label-free quantitative mass
      spectrometry (MS) and bioinformatics to characterize many protein complexes from
      Cyanothece 51142 cells grown under a 12 h light-dark cycle. We identified 1386
      proteins in duplicate biological replicates, and 64% of those proteins were
      identified as putative complexes. Pairwise computational prediction of protein
      protein interaction (PPI) identified 74 822 putative interactions, of which 2337
      interactions were highly correlated with published protein coexpressions. Many
      sequential glycolytic and TCA cycle enzymes were identified as putative
      complexes. We also identified many membrane complexes that contain cytoplasmic
      domains. Subunits of NDH-1 complex eluted in a fraction with an approximate mass
      of ~669 kDa, and subunits composition revealed coexistence of distinct forms of
      NDH-1 complex subunits responsible for respiration, electron flow, and CO2
      uptake. The complex form of the phycocyanin beta subunit was nonphosphorylated,
      and the monomer form was phosphorylated at Ser20, suggesting phosphorylation
      dependent deoligomerization of the phycocyanin beta subunit. This study provides
      an analytical platform for future studies to reveal how these complexes assemble
      and disassemble as a function of diurnal and circadian rhythms.

PMID- 30216072
TI  - Phase Transition in Monolayer Water Confined in Janus Nanopore.
AB  - The ubiquitous nature of water invariably leads to a variety of physical
      scenarios that can result in many intriguing properties. We investigate the
      thermodynamics and associated phase transitions for a water monolayer confined
      within a quasi-two-dimensional nanopore. An asymmetric nanopore constructed by
      combining a hydrophilic (hexagonal boron nitride) sheet and a hydrophobic
      (graphene) sheet leads to an ordered water structure at much higher temperatures
      compared to a symmetric hydrophobic nanopore consisting of two graphene sheets.
      The discontinuous change in the thermodynamic quantities, potential energy ( U),
      and entropy ( S) of confined water molecules computed from the all-atom molecular
      dynamics simulation trajectories, uncovers a first-order phase transition in the
      temperature range of T = 320-330 K. Structural analysis reveals that water
      molecules undergo a disorder-to-order phase transformation in this temperature
      range with a 4-fold symmetric phase persisting at lower temperatures. Our
      findings predict a novel confinement system which has the melting transition for
      monolayer water above the room temperature, and provide a microscopic
      understanding which will have important implications for other nanofludic systems
      as well.

PMID- 30216073
TI  - Debundling, Dispersion, and Stability of Multiwalled Carbon Nanotubes Driven by
      Molecularly Designed Electron Acceptors.
AB  - Carbon nanotubes (CNTs) have attracted significant attention because of their
      outstanding physical and chemical properties, and yet, their high natural
      tendency to form bundles, ropes, or aggregates, as a consequence of their strong
      pi-pi interactions, limits their solvent processing and further applications.
      Efficient processing solvents, mostly amide-based, that partially compensate for
      these strong inter-CNT pi-pi interactions have been widely reported. However, the
      yield of debundled/dispersed CNTs and the stability of subsequent dispersions in
      these solvents remain key challenges. Moreover, there are major concerns related
      to the large-scale use of conventional solvents, as they are fossil fuel based
      and intrinsically highly toxic, hence the need to identify environmentally
      friendly and safer alternatives. Herein, we address these challenges by using a
      ternary system composed of multiwalled CNTs (MWCNTs), tailored electron-deficient
      acceptors, and an organic solvent. Not only do the electron-deficient acceptors
      interrupt the inter-CNTs pi-pi interactions, thereby enabling the subsequent
      debundling and dispersion of MWCNTs aggregates in the solvent, they also act as
      stabilizers, after dispersion, by inhibiting inter-CNT pi-pi interactions and re
      agglomeration. The use of electron acceptors increases the yield by a factor of
      165 in N-methyl 2-pyrrolidone, improves the long-term stability of the debundled
      and dispersed MWCNTs, and reduces the energy input to only 30 min of mild bath
      sonication, compared with prolonged high-energy sonication reported in the
      literature. We also report for the first time, the use in MWCNT processing of a
      "green" biosolvent, dihydrolevoglucosenone, as an environmentally friendly and
      nontoxic alternative to the more conventional amide-based solvents.

PMID- 30216074
TI  - A Ring Contraction of 2,3-Di- O-Silylated Thiopyranosides To Give Thiofuranosides
      under Mildly Acidic Conditions.
AB  - A pyranose ring contraction of ethyl 1-thio-beta-d-galactopyranosides has been
      discovered that proceeds with retention of aglycon under mildly acidic conditions
      (aq TFA in CH2Cl2). Key factors for success of this rearrangement are the
      presence of bulky silyl (TIPS or TBDPS) substituents at both O-2 and O-3 and a
      free hydroxy group at C-4 (derivatives with acid-labile protective groups at O-4
      will also engage in this reaction). The rearrangement cleanly proceeds for 2,3-di
      O-TIPS derivatives with two hydroxy groups at C-4 and C-6, acid-labile TES
      groups at O-4 and O-6, or one acyl substituent (Bz, ClAc) at O-6. A possibility
      to switch the direction of the debenzylidenation reaction in 4,6- O-benzylidene
      2,3-di- O-TIPS/TBDPS derivatives by the choice of an acid (TFA, which cleanly
      gives furanose, versus AcOH, which cleaves benzylidene acetal only) may present
      an advantage in the divergent synthesis of selectively protected glycosyl donors
      (either in furanose or pyranose form) useful for the synthesis of biologically
      important oligosaccharides.

PMID- 30216075
TI  - Palladium-Catalyzed Thiomethylation via a Three-Component Cross-Coupling
      Strategy.
AB  - In this report, the combination of masked inorganic sulfur and dimethyl carbonate
      was designed to achieve thiomethylated cross coupling of aryl chlorides.
      Remarkably, this powerful strategy realized thiomethylation of nucleosides
      bearing unprotected ribose, chloride-containing pharmaceuticals with late-stage
      coupling, and herbicides possessing multiple heteroatoms and steric hindrance.
      Moreover, this protocol is practically amenable to multigram-scale synthesis with
      a lower catalysis loading and a higher yield.

PMID- 30216076
TI  - Surface-Restructuring Differences between Polyrotaxanes and Random Copolymers in
      Aqueous Environment.
AB  - In the present study, we investigated the surface reorganization behaviors and
      adsorption conformations of fibrinogen on the surface of polyrotaxanes containing
      different amounts of alpha-cyclodextrin (alpha-CD) by using surface-sensitive
      vibrational spectroscopy sum frequency generation (SFG). For comparison,
      behaviors of the surface restructuring and fibrinogen adsorption on the random
      copolymers containing similar terminal groups were also investigated. It was
      found that larger amounts of BMA moieties of polyrotaxanes form ordered surface
      structures after immersion in water for 48 h. Furthermore, the polyrotaxane
      surfaces exhibit a much higher capability of fibrinogen adsorption than the
      random copolymer surfaces. The water-induced surface restructuring of the
      polyrotaxane films slightly affects the adsorption structure of the fibrinogen
      molecules.

PMID- 30216077
TI  - Quantum Hall Effect in Electron-Doped Black Phosphorus Field-Effect Transistors.
AB  - The advent of black phosphorus field-effect transistors (FETs) has brought new
      possibilities in the study of two-dimensional (2D) electron systems. In a black
      phosphorus FET, the gate induces highly anisotropic 2D electron and hole gases.
      Although the 2D hole gas in black phosphorus has reached high carrier mobilities
      that led to the observation of the integer quantum Hall effect, the improvement
      in the sample quality of the 2D electron gas (2DEG) has however been only
      moderate; quantum Hall effect remained elusive. Here, we obtain high quality
      black phosphorus 2DEG by defining the 2DEG region with a prepatterned graphite
      local gate. The graphite local gate screens the impurity potential in the 2DEG.
      More importantly, it electrostatically defines the edge of the 2DEG, which
      facilitates the formation of well-defined edge channels in the quantum Hall
      regime. The improvements enable us to observe precisely quantized Hall plateaus
      in electron-doped black phosphorus FET. Magneto-transport measurements under high
      magnetic fields further revealed a large effective mass and an enhanced Lande g
      factor, which points to strong electron-electron interaction in black phosphorus
      2DEG. Such strong interaction may lead to exotic many-body quantum states in the
      fractional quantum Hall regime.

PMID- 30216078
TI  - Impact of Crystallographic Orientation Disorders on Electronic Heterogeneities in
      Metal Halide Perovskite Thin Films.
AB  - Metal halide perovskite thin films have achieved remarkable performance in
      optoelectronic devices but suffer from spatial heterogeneity in their electronic
      properties. To achieve higher device performance and reliability needed for
      widespread commercial deployment, spatial heterogeneity of optoelectronic
      properties in the perovskite thin film needs to be understood and controlled.
      Clear identification of the causes underlying this heterogeneity, most
      importantly the spatial heterogeneity in charge trapping behavior, has remained
      elusive. Here, a multimodal imaging approach consisting of photoluminescence,
      optical transmission, and atomic force microscopy is utilized to separate
      electronic heterogeneity from morphology variations in perovskite thin films. By
      comparing the degree of heterogeneity in highly oriented and randomly oriented
      polycrystalline perovskite thin film samples, we reveal that disorders in the
      crystallographic orientation of the grains play a dominant role in determining
      charge trapping and electronic heterogeneity. This work also demonstrates a
      polycrystalline thin film with uniform charge trapping behavior by minimizing
      crystallographic orientation disorder. These results suggest that single crystals
      may not be required for perovskite thin film based optoelectronic devices to
      reach their full potential.

PMID- 30216079
TI  - High Efficiency Si Photocathode Protected by Multifunctional GaN Nanostructures.
AB  - Photoelectrochemical water splitting is a clean and environmentally friendly
      method for solar hydrogen generation. Its practical application, however, has
      been limited by the poor stability of semiconductor photoelectrodes. In this
      work, we demonstrate the use of GaN nanostructures as a multifunctional
      protection layer for an otherwise unstable, low-performance photocathode. The
      direct integration of GaN nanostructures on n+-p Si wafer not only protects Si
      surface from corrosion but also significantly reduces the charge carrier transfer
      resistance at the semiconductor/liquid junction, leading to long-term stability
      (>100 h) at a large current density (>35 mA/cm2) under 1 sun illumination. The
      measured applied bias photon-to-current efficiency of 10.5% is among the highest
      values ever reported for a Si photocathode. Given that both Si and GaN are
      already widely produced in industry, our studies offer a viable path for
      achieving high-efficiency and highly stable semiconductor photoelectrodes for
      solar water splitting with proven manufacturability and scalability.

PMID- 30215626
TI  - Precision measurement and interpretation of inclusive W+ , W- and Z/gamma*
      production cross sections with the ATLAS detector.
AB  - High-precision measurements by the ATLAS Collaboration are presented of inclusive
      W+->l+nu , W-->l-nu- and Z/gamma*->ll ( l=e,MU ) Drell-Yan production cross
      sections at the LHC. The data were collected in proton-proton collisions at
      s=7TeV with an integrated luminosity of 4.6fb-1 . Differential W+ and W- cross
      sections are measured in a lepton pseudorapidity range |etal|<2.5 . Differential
      Z/gamma* cross sections are measured as a function of the absolute dilepton
      rapidity, for |yll|<3.6 , for three intervals of dilepton mass, mll , extending
      from 46 to 150GeV . The integrated and differential electron- and muon-channel
      cross sections are combined and compared to theoretical predictions using recent
      sets of parton distribution functions. The data, together with the final
      inclusive e+/-p scattering cross-section data from H1 and ZEUS, are interpreted
      in a next-to-next-to-leading-order QCD analysis, and a new set of parton
      distribution functions, ATLAS-epWZ16, is obtained. The ratio of strange-to-light
      sea-quark densities in the proton is determined more accurately than in previous
      determinations based on collider data only, and is established to be close to
      unity in the sensitivity range of the data. A new measurement of the CKM matrix
      element |Vcs| is also provided.

PMID- 30216080
TI  - Sequential C-C sigma-Bond Cleavage/(sp2) C-O Bond Formation via C-H
      Functionalization toward Pyranoindolones Fused with Medium-Sized Rings.
AB  - An atom-economical procedure for the synthesis of pyranoindolones fused with 7-
      or 8-membered rings has been developed. This process is realized through the
      sequential Cs2CO3-promoted C-C sigma-bond cleavage of cyclic ketoesters and a
      ZnI2-mediated selective C-H/O-H coupling reaction. Two of the C-C sigma-bonds are
      cleaved and one of the sp2 C-H bonds is functionalized during the reaction
      process. Easily accessible starting materials and broad substrate scope make this
      protocol attractive in synthetic organic chemistry.

PMID- 30216082
TI  - Synthesis of Peptide Disulfide-Bond Mimics by Using Fully Orthogonally Protected
      Diaminodiacids.
AB  - A new strategy was developed for the synthesis of peptide disulfide-bond mimics
      using fully orthogonally protected diaminodiacids. This method overcomes the
      previous problems of heavy-metal contamination and poor compatibility with Fmoc
      chemistry and provides a practical avenue for the efficient preparation of
      peptide disulfide-bond mimics.

PMID- 30215627
TI  - Search for new phenomena using the invariant mass distribution of same-flavour
      opposite-sign dilepton pairs in events with missing transverse momentum in s=13  
      Tepp collisions with the ATLAS detector.
AB  - A search for new phenomena in final states containing an e+e- or MU+MU- pair,
      jets, and large missing transverse momentum is presented. This analysis makes use
      of proton-proton collision data with an integrated luminosity of 36.1fb-1 ,
      collected during 2015 and 2016 at a centre-of-mass energy s=13TeV with the ATLAS
      detector at the Large Hadron Collider. The search targets the pair production of
      supersymmetric coloured particles (squarks or gluinos) and their decays into
      final states containing an e+e- or MU+MU- pair and the lightest neutralino (
      chi~10 ) via one of two next-to-lightest neutralino ( chi~20 ) decay mechanisms:
      chi~20->Zchi~10 , where the Z boson decays leptonically leading to a peak in the
      dilepton invariant mass distribution around the Z boson mass; and chi~20->l+l
      chi~10 with no intermediate l+l- resonance, yielding a kinematic endpoint in the
      dilepton invariant mass spectrum. The data are found to be consistent with the
      Standard Model expectation. Results are interpreted using simplified models, and
      exclude gluinos and squarks with masses as large as 1.85 and 1.3  Te at 95%
      confidence level, respectively.

PMID- 30216081
TI  - Effect and Mechanism of Tanshinone I on the Radiosensitivity of Lung Cancer
      Cells.
AB  - BACKGROUND: Resistance to radiotherapy is one of the main obstacles to improving
      cancer prognoses. To effectively destroy cancer cells, novel radiation
      sensitizers are needed. Recently, several natural products have been shown to
      exhibit promising tumor-killing properties. However, little is known about the
      specific mechanisms of these natural compounds on cancer treatment. In this
      study, after screening a high-throughput natural product library, we identified
      tanshinone I (Tan I) as a potential radiation sensitizer in lung cancer cells.
      METHODS: Lung cancer radioresistant cell lines, H358-IR and H157-IR, were first
      established to confirm the radioresistant phenotypes. After that, a natural
      product library was used to screen the potential radiation sensitizer. We further
      examined the inhibition functions of Tan I on radioresistant cancer cells via a
      series of experiments. RESULTS: Tan I significantly inhibited cell proliferation
      and clone formation, consequently enhancing radiosensitivity in radioresistant
      lung cancer cells, H358-IR and H157-IR. Stable isotope labeling of amino acids in
      cell culture (SILAC)-based quantitative proteomics indicated that Tan I
      downregulates expression of pro-oncogenic protein phosphoribosyl pyrophosphate
      aminotransferase (PPAT) in both H358-IR and H157-IR cells. Further analysis of
      molecular docking showed that Tan I is well-docked into the active pocket of the
      structure of PPAT, serving as a potential PPAT inhibitor. CONCLUSIONS: Taken
      together, these findings suggest that inhibition of the tumor promoter PPAT by
      Tan I exerts marked inhibitory effects on radioresistant lung cancer cells,
      improving radiation efficacy.

PMID- 30216083
TI  - Acidity Scale of N-Heterocyclic Carbene Precursors: Can We Predict the Stability
      of NHC-CO2 Adducts?
AB  - The acidity scale (~14 p K units) of more than 90 triazolium, imidazolium, and
      imidazolinium based NHC precursors in DMSO was established systematically by a
      well-developed computational model. The substituent effects on the acidities of
      these NHC precursors were analyzed through acidity comparison and Hammett
      correlation. The binding energy (Delta G1) of the reaction between NHC and CO2
      was also calculated and linearly correlates with the basicity of the
      corresponding NHC, which implies that the stability of the NHC-CO2 adduct is
      essentially dictated by the basicity of NHC.

PMID- 30216089
TI  - University Flunk-Out to Genomics Pioneer: An Interview with George Church, PhD.

PMID- 30216084
TI  - Synthesis of Optically Active alpha-Trifluoromethylamines by Rearrangement of
      beta-Amino-alpha-trifluoromethyl Alcohols.
AB  - The synthesis of various optically active alpha-trifluoromethylamines has been
      realized from beta-amino-alpha-trifluoromethyl alcohols via an aziridinium ion
      intermediate under kinetic conditions.

PMID- 30216094
TI  - Perspectives and Experiences with Engaging Youth and Families in Research.
AB  - Engaging youth with disabilities and families in research is critical in
      facilitating knowledge utilization to impact processes and outcomes of services
      and interventions. Organizations such as INVOLVE in the United Kingdom, the
      Canadian Institutes of Health Research and the Patient-Centered Outcomes Research
      Institute in the United States advocate for engaging stakeholders in all aspects
      of the research process. Despite these efforts, there is a need for research to
      identify best practices and approaches for stakeholder engagement in research as
      current descriptions around processes are lacking. In this perspective paper, we
      share our insights and experiences with engaging youth with disabilities and
      families as members of the research team. We offer considerations and strategies
      for stakeholder engagement, as well as identify relevant frameworks to facilitate
      stakeholder engagement in research. We encourage researchers to share and
      document their experiences with stakeholder engagement in research to provide
      guidance for others with shared interests. We hope this paper will initiate
      conversations among researchers about best practices to maximize the full
      potential of stakeholders' time and input.

PMID- 30216092
TI  - Gender Differences in Energy Expenditure During Walking With Backpack and Double
      Pack Loads.
AB  - OBJECTIVE: To investigate gender differences in energy expenditure during walking
      with backpack and double-pack loads. BACKGROUND: Studies have reported that
      energy expenditure during walking with double-pack loads is lower compared with
      backpack carriage. However, the effect of gender on energy expenditure while
      walking with these two load distribution systems has not been investigated.
      METHOD: Thirty healthy young adults (15 female and 15 male participants) walked
      on a treadmill with backpack and double-pack loads weighing 30% of their body
      weight at a speed of 0.89 m/s for 10 min. The energy expenditure in terms of
      oxygen consumption (VO2) and respiratory exchange ratio (RER) were continuously
      monitored using a portable gas analyzer throughout each walking exercise. A mixed
      design analysis of variance model was adopted to test the effects of gender,
      pack, and time on VO2 and RER. RESULTS: No time effect was observed on VO2.
      However, significant gender, pack, and interaction effects were observed. The
      lowest VO2 was found in female participants under double-pack carriage. No
      significant gender or pack differences existed in RER. However, RER significantly
      and incrementally increased in time from the 4th through 6th, 8th, and 10th min.
      CONCLUSION: This study revealed that heavy double-pack load carriage for healthy
      young female participants had significantly lower energy expenditure (normalized
      by the entire system weight, i.e., the participant's weight plus the weight of
      the pack) than that of the male participants in a 10-min walking exercise.
      APPLICATION: The findings of this study indicated that healthy young female
      participants carried a heavy double-pack with less energy cost (normalized by the
      entire system weight, i.e., the participant's weight plus the weight of the pack)
      compared with their male counterparts during a 10-min walking exercise.

PMID- 30216085
TI  - Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node
      Assessment: An Observational Cohort Study with Independent Validation.
AB  - RATIONALE: Mediastinal lymph node (MLN) enlargement on chest computed tomography
      (CT) is prevalent in patients with interstitial lung disease (ILD) and may
      reflect immunologic activation and subsequent cytokine-mediated immune cell
      trafficking. OBJECTIVES: We aimed to determine whether MLN enlargement on chest
      CT predicts clinical outcomes and circulating cytokine levels in ILD. METHODS:
      MLN measurements were obtained from chest CT scans of patients with ILD at
      baseline evaluation over a ten-year period. Patients with sarcoidosis and drug
      toxicity-related ILD were excluded. MLN diameter and location were assessed.
      Plasma cytokine levels were analyzed in a subset of patients. The primary outcome
      was transplant-free survival (TFS). Secondary outcomes included all-cause and
      respiratory hospitalizations, lung function, and plasma cytokine concentrations.
      Cox regression was used to assess mortality risk. Outcomes were assessed in three
      independent ILD cohorts. MEASUREMENTS AND MAIN RESULTS: Chest CT scans were
      assessed in 1,094 patients (mean age 64yrs; 52% male). MLN enlargement (>=10mm)
      was present in 66% (n=726) and strongly predicted TFS (HR=1.53, 95%CI=1.12
      2.10,P=0.008); and risk of all-cause and respiratory hospitalizations (IRR=1.52,
      95%CI=1.17-1.98,P=0.002; and IRR=1.71, 95%CI=1.15-2.53,P=0.008, respectively)
      when compared to subjects with MLN<10mm. Patients with MLN enlargement had lower
      lung function and decreased plasma concentrations of sCD40L (376pg/mL vs
      505pg/mL, P=0.001) compared to those without MLN enlargement. Plasma IL-10
      concentration >45pg/mL predicted mortality (HR=4.21, 95%CI=1.21-14.68,P=0.024).
      Independent analysis of external datasets confirmed these findings. CONCLUSIONS:
      MLN enlargement predicts TFS and hospitalization risk in ILD, and is associated
      with decreased levels of a key circulating cytokine sCD40L. Incorporating MLN and
      cytokine findings into current prediction models might improve ILD
      prognostication.

PMID- 30216087
TI  - Evaluation of mallear ligaments in different voxel resolutions using cone beam
      computed tomography.
AB  - OBJECTIVES:: The aim of this study was to assess the visibility of discomallear
      ligament and anterior mallear ligament together with anatomical morphometric
      measurements of petrotympanic fissure, and to determine whether the mallear
      ligaments correlate with the bone compartment changes of temporomandibular joint.
      METHODS:: Cone beam CT images of 275 patients were evaluated retrospectively. The
      visibility of discomallear and anterior mallear ligaments were evaluated by two
      observers. The petrotympanic fissure was classified into four groups. Morphologic
      features of petrotympanic fissure and mandibular fossa were also measured in
      sagittal, axial and three-dimensional cone beam CT reconstructed images.
      Pearson's chi2 test and Student's t-test were performed for statistical analysis
      of differences voxel sizes, age, gender, localization, temporomandibular joint
      and measurements (p < 0.05). Intra- and interobserver reliability was also
      performed. RESULTS:: Type 3 petrotympanic fissure was more frequent in male,
      whereas females showed Type 1 and Type 2 petrotympanic fissure structures (p <
      0.05). Anterior mallear ligament visibility on cone beam CT images was
      statistically higher in bone compartment changes of temporomandibular joint. In
      cone beam CT images, petrotympanic fissure tunnel types 1, 2, 3 and 4 were seen
      in 11.5, 35.63, 51.34 and 1.53% of patients, respectively. CONCLUSIONS::
      Knowledge of the anatomy may help in identifying temporomandibular joint pain and
      auditory symptoms due to temporomandibular disorder. Further cross-sectional
      studies with larger populations are needed to investigate the physiopathological
      relation of both disorders.

PMID- 30216088
TI  - Vigilance Tasks: Unpleasant, Mentally Demanding, and Stressful Even When Time
      Flies.
AB  - OBJECTIVE: To determine whether perceived time progression (PTP) moderates
      participants' negative reactions to vigilance tasks. BACKGROUND: Vigilance tasks
      are rated by participants to be unenjoyable and as having high levels of workload
      and stress. Based on the adage, "You are having fun when time flies," we tested
      the possibility that accelerating PTP might reduce these negative experiences.
      METHOD: Two studies were performed, involving a long 30-min and a short 12-min
      vigil. We manipulated participants' PTP by creating a mismatch between their
      expectations about how long they would perform the task and the actual time that
      they were engaged. RESULTS: PTP was significantly faster for participants who
      were led to expect that the vigilance task would last longer than it did relative
      to those led to expect that task duration would be shorter than it actually was
      and for controls for whom task duration was equal to the expected duration.
      However, accelerating PTP had no effect in either experiment on undesirable
      reactions to the vigilance tasks. Participants uniformly rated both tasks as
      unenjoyable, as having a high level of workload, and as stressful. Apparently,
      vigilance isn't fun even when time flies. CONCLUSION: Our findings greatly
      underscore the depth to which negative subjective reactions are embedded in the
      nature of vigilance tasks and therefore that these tasks can have potentially
      serious costs to participants in terms of health, safety, and productivity.
      APPLICATION: These costs must be considered at the operational level.

PMID- 30216093
TI  - CBCT image based segmentation method for tooth pulp cavity region extraction.
AB  - OBJECTIVES:: A method was proposed to segment the tooth pulp cavity region in
      cone beam CT) images, which aimed to make the extraction process more efficient
      and generate more reliable results for further research. METHODS:: Cone beam CT
      images of 50 teeth from 10 patients were randomly collected with the help of
      Peking University Hospital of Stomatology. All slice images have a ground truth
      tooth pulp cavity region delineated by two doctors manually. After necessary
      gamma transform in pre-processing stage, three kinds of information in an image
      such as greyscale, neighbour average greyscale and gradient were fused to search
      an optimal segmentation threshold by using plane intercept histogram of
      reciprocal cross entropy algorithm. With the optimal threshold, binarization was
      conducted and the tooth pulp cavity regions in slice images can be extracted.
      Qualitative and quantitative analyses compared to ground truth are involved with
      the evaluation criterion of average non-coincidence rate ([Formula: see text]).
      Independent repeated experiments were carried out to test the stability of this
      segmentation method. RESULTS:: Accurate and complete segmentation results are
      obtained. The proposed method reaches the lowest [Formula: see text] values in
      most cases and owns more competitive robustness under various interferences
      compared with the other popular segmentation methods like reciprocal cross
      entropy method, active contour-based method, region growing method and level set
      method. Quantitative analysis verified the effectiveness of this method.
      CONCLUSIONS:: The proposed method can extract tooth pulp cavity regions from
      teeth efficiently. The segmentation results of this method are more accurate
      compared to other popular methods under different circumstances and can be used
      for subsequent applications.

PMID- 30216090
TI  - Image segmentation-based volume approximation-volume as a factor in the clinical
      management of osteolytic jaw lesions.
AB  - OBJECTIVE:: Size characterization of osteolytic jaw lesions (OJL), in particular
      of neoplastic nature, is heterogeneously performed and lacks standardization in
      the medical literature and clinical practice. An OJL's volume holds promise as a
      surrogate for treatment response and prognosis. We comparatively evaluate various
      methods for size characterization of odontogenic OJLs. METHODS:: We
      retrospectively performed semiautomatic image segmentation of CBCT data sets for
      volume approximation of neoplastic (51) and non-neoplastic odontogenic OJLs
      (100). We assessed the three greatest orthogonal diameters and calculated the
      volume using the cuboid- and ellipsoid-formula. Image segmentation was carried
      out using ITK-SNAP. Image segmentation-based volume approximation served as
      reference. Intra- and inter-rater variability were evaluated at hand of Bland
      Altman-Analysis and dice similarity coefficient (DSC). RESULTS:: Concerning the
      intrarater variability, we found the DSC to be highest for image segmentation
      based volume approximation, simultaneously showing the tightest limits of
      agreement and greatest reliability. The cuboid formula showed consistent
      overestimation of the lesion's volume with a percent mean difference of -52 %
      (upper and lower limits of agreement +8.57 %  and -112.63%, respectively). In
      mean, the ellipsoid formula underestimated the lesion's volume by 10.1% (upper
      and lower limits of agreement +76.8%  and -56.6%, respectively). Inter rater
      variability was higher for formula-based volume approximation. Volume and
      multilocularity (p = 0.001) correlate with aggressiveness and growth potential.
      CONCLUSIONS:: Segmentation-based volume approximation holds great promise for
      patient individualized treatment planning and clinical management. The data
      suggest that maximum tumour diameter-based size characterization, especially the
      cuboid-formula and the maximum diameter alone, should not be recommended.

PMID- 30216096
TI  - Vested Interests and Perceived Risk of Concussion Consequences among Power-5
      College Athletes.
AB  - Concussion injuries among young athletes are a growing public health concern;
      concussion injuries pose threats to both short-term and long-term brain health.
      Significant, multidisciplinary efforts are underway to improve detection,
      diagnosis and treatment. Concussion symptoms are ambiguous and not outwardly
      visible; successful detection and diagnosis efforts depend on veridical athlete
      communication with health practitioners. To date, education programs to enhance
      reporting behaviors have not been successful. This research reports findings from
      the first phase of a project designed to understand athlete's perceived risk of
      concussion consequences with the goal of informing theory-based motivational and
      educational interventions. Using a novel theoretical approach, this research
      examines the vested interests of 435 collegiate athletes from 12 universities,
      participating in six Division I level, high concussion-risk sports, sanctioned by
      a Power-5 conference. Our findings confirm that the vestedness model predicts a
      consequential amount of variance in perceived concussion risk, perceived levels
      of concussion education, and recalled head impacts. The model identifies several
      opportunities to craft theory-based messages that can motivate reporting
      behaviors. This research contributes to the literature on concussion safety by
      offering a unique theoretical framework that accounts for factors influencing
      risk perception and takes a step in a call for deliberate, theory-based
      optimization and translation of concussion education for high-risk athletes.

PMID- 30216097
TI  - Using a Six-Domain Framework to Include Biopsychosocial Information in the
      Standard Medical History.
AB  - PROBLEM: The traditional approach to physicians' history taking is designed to
      facilitate diagnosis and treatment of biomedical conditions. However, in the 21st
      century, health is critically influenced by the interaction of biomedical
      conditions and nonbiomedical factors such as patient's ability to manage chronic
      disease and the social determinants of health. Interventions to expand routine
      history taking to include nonbiomedical factors have not been widely adopted,
      possibly due to the difficultly of incorporating long checklists into routine
      care and the inability to achieve consensus on the relevant behavioral or social
      determinants of health content applicable to all patients. INTERVENTION: In 2015
      2016, we introduced medical students to a 6-domain (biomedical and psychiatric
      conditions, behavioral health, living environment/resources, social support, and
      functional status) approach to history taking and instructed them to elicit
      information from each domain alongside the traditional approach. Students were
      required to obtain information from each domain in one admitting history or one
      daily progress note, discuss their findings with the attending physician, and
      involve members of the medical team in addressing concerns and barriers in the
      care of that patient. Students' history notes were reviewed for completeness and
      compared to those from a student control group. Students also completed a 10
      question evaluation of the model. CONTEXT: The intervention was conducted during
      a 1-month rotation on a hospitalist general medicine service from May 2015
      through August 2016. OUTCOME: Patient history and daily progress notes were
      collected from 38 fourth-year intervention students and compared to 24 control
      students on the same service from the previous year. Compared to control
      students, intervention students provided more patient information (p <= .001) in
      all nonbiomedical domains except behavioral health. Intervention students
      reported that the 6-domain model helped them identify clinical information that
      could be addressed with existing resources and prompted involvement of social
      workers, pharmacists, and nurses in care planning. They also indicated the
      framework added clinically valuable information and enhanced team-based care.
      LESSONS LEARNED: A domain-based framework can be used by medical students to
      identify clinically relevant behavioral conditions and social determinants of
      health tailored to individual patients while avoiding long standardized
      checklists. Arguably, routine collection of behavioral and social determinants of
      health is a necessary first step in enhancing physicians' awareness and skills in
      working with health care teams to address nonbiomedical determinants of patients'
      health.

PMID- 30216091
TI  - Pharmacokinetics of anticoagulants apixaban, dabigatran, edoxaban, and
      rivaroxaban in elderly Japanese patients with atrial fibrillation treated in one
      general hospital.
AB  - 1. Steady-state plasma concentrations of anticoagulants and the time since the
      previous administration in mainly outpatients with atrial fibrillation
      administered standard or reduced doses were analyzed for 110 elderly Japanese
      subjects (mean age, 76 years) treated with apixaban (2.5 or 5.0 mg twice daily),
      dabigatran etexilate (110 or 150 mg twice daily), edoxaban (30 or 60 mg once
      daily), or rivaroxaban (10 or 15 mg once daily) at one general hospital. 2. The
      pharmacokinetics in patients treated with standard and reduced doses of the four
      anticoagulants using liquid chromatography-tandem mass spectrometry were compared
      with the concentration ranges estimated using physiologically based
      pharmacokinetic modelling. Reduced doses of anticoagulants resulted in relatively
      small pharmacokinetic variations compared with the standard dose. 3. Statistical
      analyses revealed that renal impairment is likely not the sole determinant factor
      for high plasma concentrations of apixaban, dabigatran, edoxaban, and
      rivaroxaban. 4. Patients with atrial fibrillation should be treated with the
      correct doses of oral anticoagulants as specified in the package inserts (e.g.,
      reduced doses for elderly patients, patients with low body weights, and in
      combination with P-glycoprotein inhibitor drugs) to avoid excessive or
      insufficient doses of direct oral anticoagulants.

PMID- 30216095
TI  - Differential Potentiation of Retinoic Acid Effects against Human Breast Cancer
      Cells by Unsaturated Fatty Acids.
AB  - Retinoic acid (RA) and unsaturated fatty acids (UFA) are proposed as nutritional
      anticancer agents. Nonetheless, the activity of their combination on human breast
      cancer needs further study. Our aim was to evaluate this activity on the MCF-7
      and ZR-75-1 cell lines treated with 1 uM RA and 50 uM of gamma-linoleic (GLA,
      omega-6), eicosapentaenoic (EPA, omega-3), oleic (OA, omega-9), or eicosatrienoic
      (ETA, omega-9) acids. The following cellular responses were compared by ANOVA and
      Fisher test (P < 0.05): fatty acids, E-cadherin, actin (differentiation),
      conjugated dienes, gamma-glutamyltranspeptidase activity (stress), and viability,
      which were correlated by partial least squares regression. Although both cell
      lines responded differentially, RA modified unsaturated fatty acids, increased
      differentiation, reduced gamma-glutamyltranspeptidase, and viability. RA
      differentiating activity on ZR-75-1 was morphologically enhanced by UFA. Stress
      induction with gamma-glutamyltranspeptidase decrease and conjugated dienes was
      promoted by ETA in MCF-7, and EPA and OA in ZR-75-1. RA-related reduced viability
      was potentiated by EPA and OA in both lines. GLA was less active. Therefore,
      unsaturated fatty acids (omega-3/omega-9) potentiated the multitarget retinoic
      acid activity against these human breast cancer cells.

PMID- 30216100
TI  - Efficacy of the Inverted Internal Limiting Membrane Flap Technique with
      Perfluorocarbon Liquid-Mediated Selective Staining for Large Macular Hole Repair.
AB  - PURPOSE: The aim of the present study was to evaluate the efficacy of the
      inverted internal limiting membrane (ILM) flap technique that involved the use of
      a perfluorocarbon liquid (PFCL) bubble for the selective prevention of
      indocyanine green (ICG) staining of the parts of the inverted flap in contact
      with the retinal pigment epithelium for large macular hole (MH) closure.
      MATERIALS AND METHODS: This retrospective, interventional, comparative study
      included 26 patients with idiopathic large MHs (minimum diameter, > 400 um) who
      underwent vitrectomy using the inverted ILM flap technique with conventional ILM
      staining with ICG (n = 14, Group 1) or PFCL-mediated selective ILM staining with
      ICG (n = 12, Group 2). The hole closure rate, best-corrected visual acuity
      (BCVA), and optical coherence tomography findings were analyzed at baseline and
      1, 3, and 6 months after surgery in both groups. RESULTS: Hole closure was
      achieved in all the eyes. BCVA significantly improved after surgery in both
      groups (p < 0.001 for both groups), although Group 2 exhibited significantly
      better values at 3 and 6 months after surgery (p = 0.008 and 0.001 at 3 and 6
      months, respectively). The sizes of ellipsoid zone defect significantly decreased
      after surgery in both groups (p < 0.001 relative to the baseline width in both
      groups), and it was significantly smaller in Group 2 than in Group 1 at 3 (p =
      0.006) and 6 (p = 0.001) months after surgery. CONCLUSIONS: The findings of this
      study suggest that recovery of the photoreceptor layers and, consequently, the
      postoperative VA are better with the inverted ILM flap technique employing PFCL
      mediated selective ILM staining with ICG than with the technique employing
      conventional ILM staining with ICG methods for patients with large MHs.

PMID- 30216098
TI  - Medical Student Perceptions of On-Call Modalities: A Focus Group Study.
AB  - : Phenomenon: The call component of clerkship presents students with unique
      opportunities and challenges. Clerkship programs employ various call modalities,
      including traditional call, night float, and evening call. The impact of these
      call models on the student experience has not been explored in depth. APPROACH:
      Focus groups were conducted with 4th-year medical students, exploring their
      multidimensional experiences with various call modalities during clerkship.
      Transcripts were analyzed using thematic analysis. FINDINGS: Thirty-nine students
      participated in 6 focus groups. Four overarching themes were identified: (a)
      educational value conferred by clinical exposure and teaching, (b) maintaining
      quality of life and developing features of burnout, (c) formation of professional
      identity via relationships with team members, and (d) perceived quality of
      patient care provided. Students associated evening call with burnout and poor
      educational value but also better patient continuity of care. Night float and
      traditional call contributed to a sense of team bonding and had enhanced
      perceived educational value while on call but resulted in loss of formal academic
      teaching time. Insights: Call modality impacts student learning, well-being,
      professional identity formation, and patient care; however, trade-off among these
      elements exists across all call models. Enhancing the value of student call
      experience may be achieved by implementation of various purposeful changes. These
      may include creating consistency between student and resident call schedules,
      maximizing recovery time between call shifts, and avoiding scheduling of students
      for call prior to academic sessions.

PMID- 30216099
TI  - Evaluation of pharmacokinetic interactions between bicyclol and co-administered
      drugs in rat and human liver microsomes in vitro and in rats in vivo.
AB  - 1. Bicyclol is a new synthetic anti-hepatitic drug and primarily metabolized by
      CYP3A. The aim of this study was to evaluate the pharmacokinetic interactions
      between bicyclol and co-administered drugs including metformin, pioglitazone,
      atorvastatin, fenofibrate, Cyclosporin A (CsA) and tacrolimus in rat and human
      liver microsomes (RLMs/HLMs) in vitro and in rats in vivo. 2. The depletion rate
      of bicyclol in RLMs was significantly inhibited by 44.8% and 35.5% after
      preincubation with pioglitazone and fenofibrate while the metabolite formation
      rate of bicyclol in HLMs was inhibited by 26.1% and 23.9% after preincubation and
      coincubation with tacrolimus, and by 20.2% after preincubation with CsA.
      Conversely, preincubation and coincubation with bicyclol significantly inhibited
      the depletion rate of pioglitazone in RLMs by 34.1% and 27.1%, respectively, and
      the formation rate of para- and ortho-hydroxy atorvastatin in RLMs and HLMs by
      20.6-36.2%. There were no significant pharmacokinetic interactions between
      bicyclol and pioglitazone in rats after a single or multiple oral treatment. 3.
      As the selected inhibitory drug concentrations in vitro were significantly higher
      than those in clinical settings and the maximum inhibition rate did not exceed
      50%, the clinically significant interaction between bicyclol and these co
      administered drugs in humans is predicted less likely to happen.

PMID- 30216101
TI  - Embarking on a Journey of Discovery: Developing Transitional Skill Sets through a
      Scholarly Concentration Program.
AB  - PROBLEM: Medical student participation in research enhances appreciation of the
      scientific literature and the conduct of investigation, and may lead to an
      interest in academic medicine. Independent medical student research offers
      frequently overlooked opportunities to develop and assess professional practice
      abilities, including project design and implementation, interprofessional team
      communication, and time management. These skills, useful to physicians, are often
      challenging for medical students to master as they transition into clinical
      careers. To address this challenge, we designed and embedded interventional
      modalities into a highly mentored and longitudinal scholarly concentration
      component of the curriculum. INTERVENTION: The Embark scholarly concentration
      program incorporates traditional research training with the development of
      professional practice skills essential for transitioning to clinical practice.
      The program includes individualized and just-in-time components enabling student
      access to information and feedback specific to their projects and development of
      professional practice skills. CONTEXT: The Embark program is a required
      longitudinal component of the Oakland University William Beaumont School of
      Medicine undergraduate medical curriculum. The Embark program consists of courses
      that inform and facilitate a required longitudinal independent research project.
      OUTCOME: A retrospective evaluation of the Embark program's success with
      development of professional practice skills through the lens of both faculty and
      student perceptions included analysis of project records and course evaluation
      feedback. Evaluation of individual student development of transitional skill
      ability is possible through both quantitative and qualitative analysis of data
      collected from student project records. More than 80% of course evaluation
      commentary on strengths of the program addressed activities related to
      professional practice skills. To systematize the evaluation of these data
      sources, we have piloted a framework, iSAIL, designed to assess student
      development in these skills during the planning and conduct of a research
      project. LESSONS LEARNED: By developing professional practice skills in the
      context of a scholarly concentration program, medical students can build a
      foundation for future engagement in research while they develop skills to
      overcome challenges that they are likely to encounter in their clinical careers.
      Modalities designed to evaluate individualized student development of
      professional practice skills through research participation define program
      successes and may lead to the identification of additional resources needed by
      students. By offering medical students opportunities to develop professional
      practice skills within the protected environment of an independent research
      project, this scholarly concentration program provides a valuable opportunity to
      influence the early development of skills necessary throughout their clinical
      careers.

PMID- 30216086
TI  - Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease
      Caused by Mycobacterium avium Complex (CONVERT): A Prospective, Open-Label,
      Randomized Study.
AB  - Rationale Improved therapeutic options are needed for patients with treatment
      refractory nontuberculous mycobacterial lung disease caused by Mycobacterium
      avium complex (MAC). Objectives To evaluate the efficacy and safety of daily
      amikacin liposome inhalation suspension (ALIS) added to standard guideline-based
      therapy (GBT) in patients with refractory MAC lung disease. Methods Adults with
      amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite
      >=6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT
      (ALIS+GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials
      delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture
      conversion, defined as 3 consecutive monthly MAC-negative sputum cultures by
      month 6. Measurements and Main Results Enrolled patients (ALIS+GBT, n=224; GBT
      alone, n=112) were a mean 64.7 years old and 69.3% female. Most had underlying
      bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both
      (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with
      ALIS+GBT and 10 of 112 (8.9%) with GBT alone (OR, 4.22; 95% CI [2.08, 8.57];
      P<0.001). Patients in the ALIS+GBT arm vs GBT alone were more likely to achieve
      conversion (hazard ratio, 3.90; 95% CI, [2.00, 7.60]). Respiratory adverse events
      (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients
      receiving ALIS+GBT and 50.0% receiving GBT alone; serious treatment-emergent
      adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions
      Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved
      significantly greater culture conversion by month 6 than GBT alone, with
      comparable rates of serious adverse events. Clinical trial registration available
      at www.clinicaltrials.gov, ID NCT02344004.

PMID- 30216107
TI  - Acknowledgment of Reviewers, 2018.

PMID- 30216103
TI  - Pharmacokinetic modeling and simulation of etodolac following single oral
      administration in dogs.
AB  - 1. Etodolac is a nonsteroidal anti-inflammatory drug with selective
      cyclooxigenase-2 inhibition to treat pain and inflammation associated with
      osteoarthritis in humans and dogs. The aim of the study was to investigate the
      pharmacokinetics of etodolac following single oral administration of 200 mg to 10
      heathy beagle dogs. 2. The plasma concentrations of etodolac were detected using
      liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was
      conducted using noncompartmental method and modeling approaches. 3. Etodolac was
      rapidly absorbed (Tmax = 0.85 h, Ka = 1.49 h-1) and slowly eliminated (T1/2 =
      39.55 h) following oral administration to the dogs. A two-compartment
      pharmacokinetic model with first-order absorption and elimination rate constants
      was successfully explained for the pharmacokinetic aspects of etodolac in dogs.
      From a Monte Carlo simulation (1,000 repetitions), the accumulation index and
      AUCtau at steady state were predicted as 1.60 [90% confidence intervals (CI),
      1.24-2.81] and 408.18 ng.hr/mL [90% CI, 271.26-590.58 ng.hr/mL], respectively. 4.
      This study will help to enact a more accurate optimal dosing regimen of etodolac
      in dogs with osteoarthritis, and may be useful in developing novel formulation of
      etodolac for human in the future.

PMID- 30216105
TI  - Functionally relevant genetic variants of glutathione S-transferase GSTM5 in
      cynomolgus and rhesus macaques.
AB  - 1. Glutathione S-transferase (GST) is a family of enzymes important for
      conjugation with glutathione of endogenous and exogenous compounds. Human GSTM1
      null allele is associated with toxicity and cancers. Cynomolgus and rhesus
      macaques have molecular and enzymatic similarities of GSTs to humans; however,
      genetic variants have not been investigated. In macaques, instead of
      pseudogenized GSTM1, GSTM5 is a predominant GSTM isoform. 2. In this study,
      resequencing of GSTM5 in 64 cynomolgus and 31 rhesus macaques found 6 non
      synonymous variants, and 1 variant (IVS5 + 1) causing exon skip. Of these 7
      variants, 3 and 1 were found only in Indochinese and Indonesian cynomolgus
      macaques, respectively. 3. Cynomolgus GSTM5-mediated styrene 7,8-oxide and trans
      stilbene oxide conjugation activities correlated with GSTM protein levels
      immunochemically quantified in cynomolgus liver samples. Using recombinant GSTM5
      proteins, 4 of the 6 non-synonymous variants including E29Q, L96R, M166V, and
      S201N showed substantially lower metabolic activities. Moreover, a homozygote for
      E29Q and heterozygotes for S201N or IVS5 + 1 showed significantly lower
      conjugation activities in liver cytosolic fractions as compared with wild-type
      animals. 4. Therefore, the present results suggest that inter-animal variability
      of GST-dependent drug metabolism is at least partly accounted for by GSTM5
      variants in cynomolgus and rhesus macaques as preclinical animal models.

PMID- 30216102
TI  - Cognitive, Neuroanatomical, and Genetic Predictors of Executive Function in
      Healthy Children and Adolescents.
AB  - The Dimensional Change Card Sort (DCCS) is a measure of cognitive flexibility for
      children, which requires rule-use and shifting. Demographic, cognitive, regional
      cortical thickness, and genetic variables, including those related to language
      and executive function, were used to build predictive models of DCCS scores in
      556 healthy pediatric participants. Gender, age, frontal, and temporal lobe
      regions of interest, and measures of sustained attention, inhibition, and word
      reading were selected as the best predictors of DCCS performance. Results
      indicated that DCCS performance is related to a broad range of cognitive
      functions and anatomic regions associated with various levels of cognitive
      function.

PMID- 30216109
TI  - Genetic manipulation of CCN2/CTGF unveils cell-specific ECM-remodeling effects in
      injured skeletal muscle.
AB  - In skeletal muscle, extracellular matrix (ECM) remodeling can either support the
      complete regeneration of injured muscle or facilitate pathologic fibrosis and
      muscle degeneration. Muscular dystrophy (MD) is a group of genetic disorders that
      results in a progressive decline in muscle function and is characterized by the
      abundant deposition of fibrotic tissue. Unlike acute injury, where ECM remodeling
      is acute and transient, in MD, remodeling persists until fibrosis obstructs the
      regenerative efforts of diseased muscles. Thus, understanding how ECM is
      deposited and organized is critical in the context of muscle repair. Connective
      tissue growth factor (CTGF or CCN2) is a matricellular protein expressed by
      multiple cell types in response to tissue injury. Although used as a general
      marker of fibrosis, the cell type-dependent role of CTGF in dystrophic muscle has
      not been elucidated. To address this question, a conditional Ctgf myofiber and
      fibroblast-knockout mouse lines were generated and crossed to a dystrophic
      background. Only myofiber-selective inhibition of CTGF protected delta
      sarcoglycan-null ( Sgcd-/-) mice from the dystrophic phenotype, and it did so by
      affecting collagen organization in a way that allowed for improvements in
      dystrophic muscle regeneration and function. To confirm that muscle-specific CTGF
      functions to mediate collagen organization, we generated mice with transgenic
      muscle-specific overexpression of CTGF. Again, genetic modulation of CTGF in
      muscle was not sufficient to drive fibrosis, but altered collagen content and
      organization after injury. Our results show that the myofibers are critical
      mediators of the deleterious effects associated with CTGF in MD and acutely
      injured skeletal muscle.-Petrosino, J. M., Leask, A., Accornero, F. Genetic
      manipulation of CCN2/CTGF unveils cell-specific ECM-remodeling effects in injured
      skeletal muscle.

PMID- 30216104
TI  - Factors influencing people's ability to maintain their activity levels during
      treatment for soft tissue sarcoma - A qualitative study.
AB  - BACKGROUND AND PURPOSE: Soft tissue sarcoma (STS) is a rare connective tissue
      cancer treated with chemotherapy in the advanced stages. Emerging evidence
      suggests that physical activity (PA) improves symptom management and quality of
      life for people undergoing chemotherapy for advanced cancer. However, little
      research reports their perspective. METHOD: Semi-structured interviews were used
      within a phenomenological approach to explore factors that affect people's
      ability to be physically active while undergoing treatment. Six participants were
      recruited with purposive sampling. Thematic analysis was used to analyze the
      data. RESULTS: Three themes identified that PA was seen as an indicator of a
      persons' own sense of normality; a feeling of loss and uncertainty for the future
      had impacts on peoples' ability to be physically active, and finally,
      participants found it challenging to recognize their support needs as their
      activity levels reduced. Motivation to remain active was individual, and numerous
      barriers affected participants' ability to remain active as their disease
      advanced; this included a lack of specific guidance while undergoing
      chemotherapy. Participants expressed uncertainty generally in identifying and
      expressing their support needs as they faced multiple complex issues. CONCLUSION:
      Health professionals should be proactive in exploring possibilities for PA to
      mitigate the expected physical decline, and support symptom management while
      undergoing palliative chemotherapy.

PMID- 30216106
TI  - Examining collaborative leadership through interprofessional education: findings
      from a mixed methods study.
AB  - Collaborative leadership is essential as recent trends in healthcare service
      delivery necessitate interprofessional collaboration and care. Interprofessional
      education (IPE) efforts, therefore, have to prepare students for this type of
      leadership. The purpose of this study was to understand how students' perceptions
      of leadership change as a result of embedding a collaborative leadership model,
      the Social Change Model (SCM) of leadership, in an IPE course. Data were
      collected from 30 students participating in an interprofessional course through
      two interprofessional course reflections, pre/post leadership posters and poster
      reflections, and a pre/post survey. Results from paired sample t-tests suggested
      students significantly improved in their perceptions of leadership efficacy.
      These data also indicated improvements to the three group-level values of the
      SCM: collaboration, common purpose, and controversy with civility. Findings from
      the qualitative data suggest that students learned to view leadership as more of
      a team effort than the actions of a single individual and as more of a process
      than a role. Findings also revealed the benefits and challenges of using a visual
      process of poster development as a way of examining students' changes in
      perceptions of leadership over the course of the semester. Implications are
      discussed in relationship to the utility of the SCM in promoting students' shifts
      in conceptualizations of leadership that emphasizes collaboration and helps
      prepare students to engage in these ways within interprofessional teams in their
      practice.

PMID- 30216112
TI  - MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase-beta
      and is regulated by lnc-mg.
AB  - Skeletal muscle is an important and complex organ with a variety of functions in
      humans and animals. Skeletal myogenesis is a multistep and complex process, and
      increasing evidence suggests that microRNAs (miRNAs) and long noncoding RNAs
      (lncRNAs) play critical roles in skeletal myogenesis. In this study the
      expression of miR-351-5p is dynamically regulated during skeletal myogenesis in
      vitro and in vivo. Cell-counting kit-8, qRT-PCR, and EdU immunofluorescence
      analysis showed that miR-351-5p overexpression promoted the proliferation and
      inhibited the differentiation of C2C12 myoblast, whereas inhibition of miR-351-5p
      had the opposite effect. In addition, miR-351-5p mediated the regulation of
      muscle fiber type transition in vivo. In vitro, loss of miR-351-5p in muscle
      tissues promoted muscle hypertrophy and increased slow-twitch fibers in the
      gastrocnemius muscles of mice. Luciferase reporter assay and functional analyses
      demonstrated that lactamase beta ( LACTB) is a direct target of miR-351-5p
      involved in the regulation of skeletal myogenesis. Expression levels of a
      myogenesis-associated lncRNA ( lnc-mg) correlated negatively with miR-351-5p and
      positively with LACTB during C2C12 myoblast proliferation and differentiation.
      Further analyses showed that lnc-mg acted as a molecular sponge for miR-351-5p,
      demonstrating its involvement in the negative regulation of LACTB by miR-351-5p
      during skeletal myogenesis. These findings indicate that miRNA-351-5p functions
      in skeletal myogenesis by targeting LACTB and is regulated by lnc-mg, supporting
      the role of the competing endogenous RNA network in skeletal myogenesis.-Du, J.,
      Zhang, P., Zhao, X., He, J., Xu, Y., Zou, Q., Luo, J., Shen, L., Gu, H., Tang,
      Q., Li, M., Jiang, Y., Tang, G., Bai, L., Li, X., Wang, J., Zhang, S., Zhu, L.
      MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase beta
      and is regulated by lnc-mg.

PMID- 30216118
TI  - A Heartfelt Message, Estrogen Replacement Therapy: Use It or Lose It.
AB  - The issue of cardiovascular and cognitive health in women is complex. During the
      premenopausal phase of life women have healthy blood pressure (BP) levels that
      are lower than age-matched men and they have less cardiovascular disease.
      However, in the post-menopausal stage of life women's BP increases and they are
      increasingly susceptible to cardiovascular disease, cognitive impairments and
      dementia, exceeding the incidence in men. The major difference between pre- and
      post-menopausal women is the loss of estrogen. Thus, it seemed logical that post
      menopausal estrogen replacement therapy, with or without a progestin, generally
      referred to as menopausal hormone treatment (MHT), would prevent these adverse
      sequelae. However, despite initially promising results, a major randomized
      clinical trial refuted the benefits of MHT leading to it falling from favor.
      However, reappraisal of this study in the framework of a "Critical Window", or
      "Timing Hypothesis" has changed our perspective on the benefit to risk ratio of
      MHT and this review discusses the historical, current and future approaches to
      MHT.

PMID- 30216110
TI  - Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen
      species and attenuates the survival and resorption function of osteoclasts by
      modulating integrin signaling.
AB  - Many bone diseases, such as osteoporosis and rheumatoid arthritis, are attributed
      to an increase in osteoclast number or activity; therefore, control of
      osteoclasts has significant clinical implications. This study shows how
      skullcapflavone II (SFII), a flavonoid with anti-inflammatory activity, regulates
      osteoclast differentiation, survival, and function. SFII inhibited
      osteoclastogenesis with decreased activation of MAPKs, Src, and cAMP response
      element-binding protein (CREB), which have been known to be redox sensitive. SFII
      decreased reactive oxygen species by scavenging them or activating nuclear factor
      erythroid 2-related factor 2 (Nrf2), and its effects were partially reversed by
      hydrogen peroxide cotreatment or Nrf2 deficiency. In addition, SFII attenuated
      survival, migration, and bone resorption, with a decrease in the expression of
      integrin beta3, Src, and p130 Crk-associated substrate, and the activation of
      RhoA and Rac1 in differentiated osteoclasts. Furthermore, SFII inhibited
      osteoclast formation and bone loss in an inflammation- or ovariectomy-induced
      osteolytic mouse model. These findings suggest that SFII inhibits
      osteoclastogenesis through redox regulation of MAPKs, Src, and CREB and
      attenuates the survival and resorption function by modulating the integrin
      pathway in osteoclasts. SFII has therapeutic potential in the treatment and
      prevention of bone diseases caused by excessive osteoclast activity.-Lee, J.,
      Son, H. S., Lee, H. I., Lee, G.-R., Jo, Y.-J., Hong, S.-E., Kim, N., Kwon, M.,
      Kim, N. Y., Kim, H. J., Lee, Y. J., Seo, E. K., Jeong, W. Skullcapflavone II
      inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates
      the survival and resorption function of osteoclasts by modulating integrin
      signaling.

PMID- 30216115
TI  - Tefillin Use Induces Remote Ischemic Preconditioning Pathways in Healthy Males.
AB  - OBJECTIVES: This study assessed whether tefillin use (tight, non-occlusive,
      wrapping of the arm) elicits a remote ischemic preconditioning (RIPC) like effect
      in subjects with both acute and chronic use. BACKGROUND: RIPC, created by short
      bursts of ischemia/reperfusion, has not been successfully taken to the bedside.
      Several large population studies have found that Orthodox Jewish males (who wear
      tefillin almost daily) have decreased cardiovascular mortality compared to non
      Orthodox counterparts. We hypothesized that tefillin use is a relevant component
      in triggering a preconditioning effect. METHODS: Twenty Jewish men were enrolled,
      9 daily tefillin users (conditioned) and 11 non-users of tefillin as controls
      (naive). Subjects were evaluated for adherence to traditional Jewish practice,
      blood drawn for analysis of circulating cytokines and monocyte function and
      underwent brachial flow mediated dilation to evaluate vascular reactivity at
      baseline (basal) and after 30 minutes of using tefillin (acute treatment).
      RESULTS: Under basal conditions, both groups had similar peak systolic velocity
      (SV), diameter, and flow volume, though the conditioned group had higher SV at
      120 seconds post-deflation (p=0.05). Acute tefillin use augmented artery diameter
      and flow volume in both groups, with conditioned subjects experiencing higher SV
      than controls at 90 and 120 seconds post-deflation (p=0.03 and p=0.02,
      respectively). Conditioned subjects had decreased inflammation, monocyte
      migration and adhesion, and endothelial activation compared to controls at
      baseline. Acute use of tefillin did not significantly alter monocyte function in
      either group. CONCLUSIONS: Acute tefillin use improves vascular function while
      chronic tefillin use is associated with an anti-inflammatory RIPC-like phenotype.

PMID- 30216111
TI  - beta-Arrestin1 enhances liver fibrosis through autophagy-mediated Snail
      signaling.
AB  - GPCR mediator beta-arrestins (beta-arr1 and beta-arr2) regulate a variety of
      physiologic and pathologic processes, including hepatocellular carcinogenesis.
      However, the role of beta-arrestins in liver fibrosis remains unknown. beta-arr1,
      but not beta-arr2, was upregulated in liver fibrotic tissues in both humans and
      mice; moreover, autophagy was increased. beta-arr1 deficiency or autophagic
      inhibitor 3-methyladenine (3-MA) significantly blocked autophagy and
      downregulated liver fibrosis. Furthermore, beta-arr1 enhanced hepatocyte
      compensatory proliferation, and hepatic stellate cell growth with activation via
      autophagy resulted in liver fibrosis. In the fibrosis, beta-arr1 promoted nuclear
      translocation of Snail by downregulation of glycogen synthase kinase-3beta, and
      the nuclear translocation of Snail was abrogated either by beta-arr1 deficiency
      or by 3-MA. These results suggest that beta-arr1 promotes liver fibrosis via
      autophagy-mediated Snail signaling, and beta-arr1 may be a therapeutic target for
      liver fibrosis.-Tan, S., Lu, Y., Xu, M., Huang, X., Liu, H., Jiang, J., Wu, B.
      beta-Arrestin1 enhances liver fibrosis through autophagy-mediated Snail
      signaling.

PMID- 30216113
TI  - Hemodynamic forces using 4D flow MRI: an independent biomarker of cardiac
      function in heart failure with left ventricular dyssynchrony?
AB  - Aims Heart failure patients with LV dyssynchrony often do not respond to cardiac
      resynchronization therapy (CRT), indicating that the pathophysiology is
      insufficiently understood. Intracardiac hemodynamic forces computed from 4D flow
      MRI have been proposed as a new measure of cardiac function. We therefore aimed
      to investigate how hemodynamic forces are altered in LV dyssynchrony. Methods 31
      patients with heart failure and LV dyssynchrony and 39 controls underwent cardiac
      magnetic resonance imaging with acquisition of 4D flow. Hemodynamic forces were
      computed using the Navier-Stokes equations and integrated over the manually
      delineated LV volume. The ratio between transverse (lateral-septal and inferior
      anterior) and longitudinal (apical-basal) forces was calculated for systole and
      diastole separately and compared with QRS duration, aortic valve opening delay,
      global longitudinal strain and ejection fraction. Results Patients exhibited
      hemodynamic force patterns which were significantly altered compared to controls,
      including loss of longitudinal forces in diastole (force ratio, controls vs
      patients: 0.32 vs 0.90, p<0.0001), and increased transverse force magnitudes.
      Systolic force ratio was correlated with global longitudinal strain and EF
      (p<0.01). Diastolic force ratio separated patients from controls (AUC=0.98,
      p<0.0001) but was not correlated to other dyssynchrony measures (p>0.05 for all).
      Conclusion Hemodynamic forces by 4D flow represents a new approach to
      quantification of left ventricular dyssynchrony. Diastolic force patterns
      separate healthy from diseased ventricles. Different force patterns in patients
      indicates possible use of force analysis for risk stratification and CRT
      implantation guidance.

PMID- 30216117
TI  - Chronic stimulation of the Sigma-1 receptor ameliorates autonomic nerve
      dysfunction and atrial fibrillation susceptibility in rat models of depression.
AB  - Aims The present study assessed the effect of Sigma-1 receptor (S1R) stimulation
      on autonomic nerve dysfunction and atrial fibrillation susceptibility in rat
      depression models. Methods and Results Male rats were randomly divided into four
      treatment groups for four weeks: saline (CTL), saline+ intragastric
      administration of SA4503 (agonist of the S1R, CTS), chronic unpredictable mild
      stress (CUMS) to produce depression(MDD), and CUMS+ intragastric administration
      of SA4503 (MDS). After 4 weeks, depression-like behaviors, such as sucrose
      preference, body weight, and immobility during forced swimming improved in the
      MDS group. Compared with CTL, MDD showed augmented sympathetic activity, reduced
      parasympathetic activity, decreased heart rate variability, and significantly
      lowered S1R expression in the atrium and in hippocampal tissues (all P<0.01).
      However, the MDS group showed mitigation of most of the above alterations and
      improved electrical remodeling (all P<0.01). Furthermore, the MDS group showed
      shortened activation latencies, increases in the effective refractory period, and
      lower frequency of AF incidence duration and fibrosis compared to MDD (all
      P<0.01). Conclusions The results indicate that S1R stimulation reduces
      sympathetic activity and atrial fibrillation susceptibility by improving
      depressive behaviours, modulating cardiac autonomic nerve balance, lightening
      nerve remodeling, and up-regulating S1R expression.

PMID- 30216114
TI  - Human Fetal Hearts with Tetralogy of Fallot have Altered Fluid Dynamics and
      Forces.
AB  - Studies suggested the effect of blood flow forces in pathogenesis and progression
      of some congenital heart malformations other than the Tetralogy of Fallot (TOF).
      It is thus of interest to study the fluid mechanic environment of the malformed
      prenatal heart, especially when little is known in the fetal TOF. In this study,
      we performed patient-specific ultrasound-based flow simulations of 3 TOF and 7
      normal human fetal hearts. TOF right ventricles (RV) had smaller end-diastolic
      volumes (EDV) but similar stroke volumes (SV), while TOF left ventricles (LV) had
      similar EDV but slightly increased SV compared to normal ventricles. Simulation
      showed that TOF ventricles had elevated systolic intra-ventricular pressure
      gradient (IVPG), and required additional energy for ejection, but IVPG elevations
      were considered to be mild relative to arterial pressure. TOF RV and LV had
      similar pressures due to equalization via ventricular septal defect (VSD).
      Further, relative to normal, TOF RVs had increased diastolic wall shear stresses
      (WSS), but TOF LVs were not. This was caused by high tricuspid inflow that
      exceeded RV stroke volume, leading to right-to-left shunting and chaotic flow
      with enhanced vorticity interaction with the wall to elevate WSS. Two of the
      three TOF RVs but none of the LVs had increased thickness. As pressure elevations
      were mild, we hypothesized that pressure and WSS elevation could play a role in
      the RV thickening, among other causative factors. Finally, the endocardium
      surrounding the VSD consistently experienced high WSS due to RV-to-LV flow shunt
      and high flow rate through the over-riding aorta.

PMID- 30216116
TI  - Smooth muscle-specific biomarker for abdominal aortic aneurysm: a beacon for the
      silent killer.

PMID- 30216119
TI  - Chemerin receptor blockade improves vascular function in diabetic obese mice via
      redox-sensitive- and Akt-dependent pathways.
AB  - Chemerin and its G protein-coupled receptor (ChemR23) have been associated with
      endothelial dysfunction, inflammation and insulin resistance. However, the role
      of chemerin on insulin signalling in the vasculature is still unknown. We aimed
      to determine whether chemerin reduces vascular insulin signalling and whether
      there is interplay between chemerin/ChemR23, insulin resistance and vascular
      complications associated with type 2 diabetes (T2D). Molecular and vascular
      mechanisms were probed in mesenteric arteries and cultured vascular smooth muscle
      cells (VSMC) from C57BL/6J, non-diabetic lean db/m and diabetic obese db/db mice
      as well as in human microvascular endothelial cells (HMEC). Chemerin decreased
      insulin-induced vasodilatation in C57BL/6J mice, an effect prevented by CCX832
      (ChemR23 antagonist) treatment. In VSMC, chemerin, via oxidative stress- and
      ChemR23-dependent mechanisms, decreased insulin-induced Akt phosphorylation,
      GLUT4 translocation to the membrane and glucose uptake. In HMEC, chemerin
      decreased insulin-activated nitric oxide signalling. AMPK phosphorylation was
      reduced by chemerin in both HMEC and VSMC. CCX832 treatment of db/db mice
      decreased body weight, insulin and glucose levels and vascular oxidative stress.
      CCX832 also partially restored vascular insulin responses in db/db and high fat
      diet (HFD)-fed mice. Our novel in vivo findings highlight chemerin/ChemR23 as a
      promising therapeutic target to limit insulin resistance and vascular
      complications associated with obesity-related diabetes.

PMID- 30216108
TI  - SCC-S2 Facilitates Tumor Proliferation and Invasion via Activating Wnt Signaling
      and Depressing Hippo Signaling in Colorectal Cancer Cells and Predicts Poor
      Prognosis of Patients.
AB  - SCC-S2 overexpression has been implicated in several human cancers, its
      correlation with prognosis and the mechanism how it reserved biological roles are
      still uncertain. The current study demonstrated that, in 142 archived colorectal
      carcinoma (CRC) tissue samples, SCC-S2 expression was significantly correlated
      with higher histological grade ( p=0.001), tumor invasion ( p=0.001), advanced
      Dukes staging ( p=0.002), positive regional lymph node metastasis ( p=0.024), and
      poor overall survival ( p<0.001). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) and Transwell assays showed that SCC-S2
      significantly promoted the proliferation and invasion. SCC-S2 expression was also
      accompanied by the overexpression CyclinD1, matrix metalloproteinase-7 (MMP-7),
      active-beta-catenin, yes-associated protein (YAP), and connective tissue growth
      factor (CTGF), as well as the depression of p-large tumor suppressor kinase 1 (p
      LATS1) and p-YAP. Moreover, SCC-S2 interacted and colocalized with LATS1, the
      interaction may interrupt Hippo signaling and thereafter activate canonical Wnt
      signaling. In conclusion, our data suggested that SCC-S2 was associated with the
      progression and unfavorable prognosis of CRCs. Meanwhile, SCC-S2 facilitated
      canonical Wnt signaling and its downstream effectors (CyclinD1, MMP-7) and
      promoted tumor proliferation and invasion, which depended on the inhibition of
      Hippo signaling induced by SCC-S2-LATS1 interaction. These results indicated that
      SCC-S2 might be used as a novel target for the prevention and treatment of
      colorectal cancer.

PMID- 30216121
TI  - Sex differences in endothelial function important to vascular health and overall
      cardiovascular disease risk across the lifespan.
AB  - Diseases of the cardiovascular system are the leading cause of morbidity and
      mortality in men and women in developed countries, and CVD is becoming more
      prevalent in developing countries. Atherosclerotic cardiovascular disease (CVD)
      prevalence in men is greater than in women until menopause, when the prevalence
      of CVD increases in women until it exceeds that of men. Endothelial function is a
      barometer of vascular health and a predictor of atherosclerosis that may provide
      insights into sex differences in CVD, as well as how and why CVD risk drastically
      changes with menopause. Studies of sex differences in endothelial function are
      conflicting, with some studies showing earlier decrements in endothelial function
      in men compared to women, while others showing similar age-related declines
      between the sexes. Because the increase in CVD risk coincides with menopause, it
      is generally thought that female hormones, in particular estrogens, are
      cardioprotective. Further, it is often proposed that androgens are detrimental.
      In truth, the relationships are more complex. This review will first address
      female and male sex hormones and their receptors, and how these interact with the
      cardiovascular system, particularly the endothelium, in healthy young women and
      men. Second, we will address sex differences in sex steroid receptor-independent
      mechanisms controlling endothelial function, focusing on the vascular endothelin
      and the renin-angiotensin systems, in healthy young women and men. Finally, we
      will discuss sex differences in age-associated endothelial dysfunction, focusing
      on the role of attenuated circulating sex-hormones in these effects.

PMID- 30216122
TI  - Progression of myocardial ischemia leads to unique changes in immediate early
      gene expression in the spinal cord dorsal horn.
AB  - The pathological consequences of ischemic heart disease involve signaling through
      the autonomic nervous system (ANS). While early activation may serve to maintain
      hemodynamic stability, persistent aberrant sympatho-excitation contributes to the
      development of lethal arrhythmias and heart failure. We hypothesize that as
      myocardium reacts and remodels to ischemic injury over time, there is an
      analogous sequence of gene expression changes in the thoracic spinal cord dorsal
      horn, the processing center for incoming afferent fibers from the heart to the
      central nervous system. Acute and chronic myocardial ischemia (MI) was induced in
      a large animal model of Yorkshire pigs and the thoracic dorsal horn of treated
      animals, along with control non-ischemic pigs, was harvested for transcriptome
      analysis. We identified 32 differentially expressed genes between healthy and
      acute ischemia cohorts and 46 differentially expressed genes between healthy and
      chronic ischemia cohorts. The canonical immediate early gene (IEG) c-fos was up
      regulated following acute MI along with fosB, dusp1, dusp2, and egr2. Following
      chronic MI, there was a persistent yet unique activation of immediate early genes
      including: fosB, nr4a1, nr4a2, nr4a3, egr3, and tnfaip3. In addition,
      differentially expressed genes from the chronic MI signature were enriched in
      pathways linked to apoptosis, immune regulation, and a stress response. These
      findings support a dynamic progression of gene expression changes in the dorsal
      horn with maturation of myocardial injury and they may explain how early adaptive
      ANS responses can maintain hemodynamic stability while prolonged maladaptive
      signals can predispose patients to arrhythmias and heart failure.

PMID- 30216120
TI  - Exercise-induced shift in right ventricular contraction pattern: novel marker of
      athlete's heart?
AB  - BACKGROUND: Data is limited about the functional adaptation of the right
      ventricle (RV) to intense exercise. Our aim was to characterize the RV mechanical
      pattern in top-level athletes using 3D echocardiography. METHODS AND RESULTS: A
      total of 60 elite water polo athletes (19+/-4 years, 17+/-6 hours of
      training/week, 50% female) and 40 healthy, sedentary controls were enrolled. We
      measured RV end-diastolic volume index (RVEDVi) and ejection fraction (RVEF)
      using dedicated software. Furthermore, we have determined RV global longitudinal
      (RV GLS) and circumferential strain (RV GCS) and the relative contribution of
      longitudinal (LEF) and radial ejection fraction (REF) to RVEF using the ReVISION
      method. Athletes also underwent cardiopulmonary exercise testing (VO2/kg).
      Athletes had significantly higher RVEDVi compared to controls (athletes vs.
      controls; 88+/-11 vs. 65+/-10 ml/m2, p<0.001), however, they also demonstrated
      lower RVEF (56+/-4 vs. 61+/-5 %, p<0.001). RV GLS was comparable between the two
      groups (-22+/-5 vs. -23+/-5 %, p=0.24), while RV GCS was significantly lower in
      athletes (-21+/-4 vs. -26+/-7 %, p<0.001). Athletes had higher longitudinal and
      lower radial contribution to RVEF (LEF/RVEF: 0.50+/-0.07 vs. 0.42+/-0.07,
      p<0.001; REF/RVEF: 0.33+/-0.08 vs. 0.45+/-0.08, p<0.001). Moreover, the pattern
      of RV functional shift correlated with VO2/kg (LEF/RVEF: r=0.30, p<0.05;
      REF/RVEF: r=-0.27, p<0.05). CONCLUSION: RV mechanical adaptation to long term,
      intense exercise imply a functional shift: the relative contribution of
      longitudinal motion to global function is increased, while the radial shortening
      is significantly decreased in athletes. Moreover, this functional pattern
      correlates with aerobic exercise performance, representing a potential new
      resting marker of athlete's heart.

PMID- 30216123
TI  - Long-Term Risk of Venous Thromboembolism in Survivors of Childhood Cancer: A
      Report From the Childhood Cancer Survivor Study.
AB  - Purpose To estimate the incidence of late-occurring venous thromboembolism (VTE)
      among survivors of childhood cancer and to identify risk factors for VTE to
      facilitate diagnosis and prevention. Methods The Childhood Cancer Survivor Study
      is a multi-institutional cohort of 24,355 5-year childhood cancer survivors
      (diagnosed between 1970 and 1999; median age at last follow-up, 28.7 years
      [range, 5.6 to 58.9 years]; median follow-up since diagnosis, 21.3 years [range,
      5.0 to 39.2 years]) and 5,051 sibling participants. The primary end point was
      self-reported late (>= 5 years after cancer diagnosis) VTE. Rate ratios (RRs)
      were estimated with multivariable piecewise exponential models. Results Late VTE
      incidence among survivors and siblings was 1.1 and 0.5 events per 1,000 person
      years, respectively (RR, 2.2; 95% CI, 1.7 to 2.8), with 2.5 excess events per 100
      survivors over 35 years. Among survivors, risk factors for VTE were female sex
      (RR, 1.3; 95% CI, 1.1 to 1.6), cisplatin (reference none; 1 to 199 mg/m2: RR, 3.0
      [95% CI, 1.4 to 6.5]; 200 to 399 mg/m2: RR, 1.9 [95% CI, 1.0 to 3.6]; >= 400
      mg/m2: RR, 2.0 [95% CI, 1.2 to 3.3]), l-asparaginase (RR, 1.3; 95% CI, 1.0 to
      1.7), obesity or underweight (reference body mass index [BMI] 18.5 to 24.9 kg/m2;
      BMI >= 30.0 kg/m2: RR, 1.6 [95% CI, 1.2 to 2.0]; BMI < 18.5 kg/m2: RR, 2.4 [95%
      CI, 1.7 to 3.4]), and late cancer recurrence or subsequent malignant neoplasm
      (RR, 4.6; 95% CI, 3.6 to 5.8). Among lower-extremity osteosarcoma survivors, limb
      salvage (reference amputation; RR, 3.1; 95% CI, 1.2 to 7.5) and cisplatin 200 to
      399 or >= 400 mg/m2 (reference none; RR, 4.0 [95% CI, 1.1 to 14.6] and 2.9 [95%
      CI, 1.1 to 8.0], respectively) were independently associated with late VTE. VTE
      was associated with increased risk for nonexternal cause late mortality (RR, 1.9;
      95% CI, 1.6 to 2.3). Conclusion Childhood cancer survivors are at increased risk
      for VTE across their lifespan and a diagnosis of VTE increases mortality risk.
      Interventions that target potentially modifiable comorbidities, such as obesity,
      warrant consideration, with prophylaxis for high-risk survivors, including those
      treated with cisplatin and limb-sparing approaches.

PMID- 30216125
TI  - CNS Metastases in Epidermal Growth Factor Receptor Mutation-Positive Non-Small
      Cell Lung Cancer: Impact on Health Resource Utilization.
AB  - PURPOSE:: Patients with epidermal growth factor receptor (EGFR) mutation-positive
      (EGFRm) non-small-cell lung cancer commonly experience disease progression in the
      CNS. Here, we assess the impact of CNS disease on resource utilization and
      outcomes in patients who are EGFRm. METHODS:: We completed a retrospective review
      of all advanced patients who were EGFRm, referred to BC Cancer, and treated with
      a first- and/or second-generation EGFR tyrosine kinase inhibitor from 2010 to
      2015. Baseline characteristics, systemic treatment, and CNS management were
      collected. We compared health resource utilization (HRU) between patients with
      CNS-negative disease and those with CNS metastases from the median time of CNS
      metastases diagnosis to death or last follow-up (9.1 months) and at 9 months
      preceding death or last follow-up for the CNS-negative group. RESULTS:: Four
      hundred ninety-nine patients were referred, of which 68% were female; 51% were of
      Asian ethnicity; and 57%, 37%, and 6% were exon 19, 21, or other, respectively;
      with a median age of 66 years. Two hundred twenty-nine (46%) of 499 patients
      developed CNS metastases-39% at diagnosis and 61% over the course of disease. CNS
      metastases were managed with surgery with or without whole-brain radiotherapy
      (WBRT; 13%) WBRT alone (73%), stereotactic radiosurgery with or without WBRT
      (5%), or no CNS-directed therapy (9%). The median time from the development of
      CNS metastases diagnosis to death was 9.1 months. CNS-negative patients used less
      HRU versus patients that were CNS-positive in the 9 months preceding death or
      last follow-up-in the average number of clinic visits (8.53 v 12.71,
      respectively; P < .001), hospitalizations (0.43 v 0.76, respectively; P < .001),
      CNS imaging investigations (0.52 v 2.65, respectively; P < .001), emergency room
      visits (0.03 v 0.14, respectively; P = .001), palliative care unit admission (8%
      v 10%, respectively; P = .64), and hospice admission (3% v 19%, respectively; P <
      .001). CONCLUSION:: The incidence of CNS metastases in patients with EGFRm is
      high and associated with increased HRU. Prevention or delay of CNS metastases
      with newer systemic therapy options may translate into lower resource
      utilization.

PMID- 30216127
TI  - Environmental and Management Factors Associated with Bacterial Diseases of Onion
      in Pennsylvania.
AB  - Bacterial diseases of onion may result in over 60% yield loss in crops grown in
      the Mid-Atlantic region, even when managed with recommended chemical and cultural
      practices. To identify environmental and production factors associated with the
      high incidence of bacterial rots in Pennsylvania, data on 32 environmental and
      management variables ranging from soil temperature to foliar nutrients were
      recorded during three visits to each of 28 and 26 fields, surveyed in 2011 and
      2012, respectively. Multiple linear regression indicated negative relationships
      between foliar nitrogen and carbon at midseason and total incidence of bacterial
      rots. Soil temperatures near the physiological onset of bulbing were positively
      related to bacterial rots in multiple datasets. These results suggest greater
      complexity may be necessary for N fertility recommendations: timing of inorganic
      N application should be considered in addition to the seasonal N rate applied.
      Lower soil temperatures, particularly near the physiological onset of bulbing,
      may also reduce the incidence of bacterial rots of onion.

PMID- 30216128
TI  - MOLECULAR IDENTIFICATION OF AVIAN VIRUSES IN NEOTROPIC CORMORANTS ( PHALACROCORAX
      BRASILIANUS) IN CHILE.
AB  - We identified two RNA (paramyxovirus and coronavirus) and two DNA (adenovirus and
      herpesvirus) viruses in a common aquatic bird, the Neotropic Cormorant (
      Phalacrocorax brasilianus), and determined their phylogenetic relationships to
      other global circulating variants. We analyzed 104 cloacal swabs from individuals
      collected at locations in Central Chile. Sequences were obtained from amplicons
      using consensus primers targeting conserved genes of the virus families
      Paramyxoviridae, Coronaviridae, Adenoviridae, and Herpesviridae. A total of 20.2%
      of the samples was positive for coronavirus, 8.7% for adenovirus, and 3.8% for
      herpesvirus. No paramyxoviruses were detected. All coronaviruses were identified
      as viruses of the Gammacoronavirus genus, closely related to the infectious
      bronchitis virus clade (bootstrap clade support=75%). All adenovirus samples were
      identified as Aviadenovirus, related to a gull and falcon adenovirus (Bayesian
      posterior probability=0.86). The herpesviruses identified were related to the
      infectious laryngotracheitis virus ( Gallid herpesvirus 1) of the genus Iltovirus
      (bootstrap clade support=99%). We provide information about the diversity of
      viruses circulating among apparently healthy Neotropic Cormorants.

PMID- 30216126
TI  - Identification of Virulences of the Rust Fungus Melampsora larici-populina
      Occurring in Chile.
AB  - Melampsora larici-populina Kleb. is a Eurasian species that causes leaf rust of
      many species of Populus from sections Tacamahaca and Aigeiros. This rust has been
      inadvertently introduced to many parts around the world affecting poplar species
      that grow naturally, which may be susceptible to this fungus. In Chile, early
      European settlers introduced poplars; rust, attributed to M. larici-populina, has
      been reported in these trees since 1918. However, a modern confirmation has been
      lacking, and pathogenic variation of the Chilean population of M. larici-populina
      has not been investigated. Using a morphological analysis of urediniospores and
      sequencing of internal transcribed spacer (ITS) regions, we confirmed the
      presence of M. larici-populina in Chile. ITS regions exhibited 100% homology with
      M. larici-populina. Scanning electron microscopy showed that spores were 26 to 47
      um in length, 13 to 16 um in width, and echinulate except for apices, which are
      smooth, characteristics described for this species of rust. The variability of M.
      larici-populina is characterized by the presence of pathotypes, which allows the
      fungus to infect despite the resistance of certain poplar hybrids. We concluded
      that the identified spores belong to M. larici-populina, with virulences 1, 2, 3,
      4, 5, and 6. These results describe variation in virulence of M. larici-populina,
      which suggests the presence of a sexual stage in Chile.

PMID- 30216129
TI  - Mortality of Little Brown Bats ( Myotis lucifugus carissima) Naturally Exposed to
      Microcystin-LR.
AB  - We describe a die-off of little brown bats ( Myotis lucifugus carissima)
      associated with acute intoxication with microcystin-LR in 2016 at Scofield
      Reservoir in Utah. High levels of this cyanotoxin in water from the reservoir and
      gastrointestinal content of bats supported this diagnosis.

PMID- 30216131
TI  - Perception Counts: The Relationships of Inner Perceptions of Trauma and PTSD
      Symptoms Across Time.
AB  - OBJECTIVE: This study examined how inner perceptions that develop in the
      aftermath of exposure to trauma attenuate the association between posttraumatic
      symptoms across time and what the reciprocal relations between inner perceptions
      of trauma and posttraumatic symptoms are. METHOD: The present article is based on
      two studies. The data in Study 1 are drawn from three waves of a longitudinal
      study of community-dwelling midlife adults and older adults residing in the south
      of Israel. In Wave 1, 339 participants were interviewed (mean age = 65.44, SD =
      9.77). Of these participants, 170 and 132, respectively, participated in Waves 2
      (one year later) and 3 (two years later). Posttraumatic stress symptoms were self
      reported in all three waves. Inner perceptions of trauma were assessed with the
      Subjective Traumatic Outlook scale (STO) and Centrality of Event Scale (CES),
      administered at Wave 3. Study 2 is drawn from two waves of research of young
      adults. Wave 1 included 138 participants (mean age = 32.01, SD = 10.57) from a
      convenience sample. At Wave 2, 128 participants were interviewed again a month
      later. Participants reported their level of posttraumatic stress symptoms and
      completed the STO and the CES in both waves. RESULTS: In Study 1, analyses showed
      stronger associations between posttraumatic symptoms across waves among those who
      reported higher subjective traumatic outlook and higher centrality of events. In
      Study 2, significant reciprocal relationships between PTSD and STO were found,
      but whereas the W1 PTSD-W2 CES path was significant, the W1 CES-W2 PTSD path was
      not. CONCLUSIONS: The findings emphasize that overintegration and especially
      disintegration of the pretraumatic identity with traumatic experiences are
      associated with the deleterious effects of long-lasting exposure to traumatic
      events.

PMID- 30216132
TI  - Assessing psychache as a suicide risk variable: Data with the Portuguese version
      of the psychache scale.
AB  - Several studies have consistently related psychological pain to suicide risk.
      Psychache, according to Shneidman's perspective and measured by the Psychache
      Scale has been confirmed as an important variable in risk prediction. In the
      present study, we evaluated psychache as a construct related to suicide risk
      using data obtained with the Portuguese version of the Psychache Scale translated
      from the original English version. A community sample of 628 individuals
      responded to the Portuguese version of the Psychache Scale, the Suicidal Behavior
      Questionnaire-Revised, the CES-D Scale, the Beck Hopelessness Scale, and the
      Suicide Ideation Questionnaire. Results supported the unidimensional scoring of
      the Psychache scale, its ability to differentiate between individuals at-risk for
      suicide from individuals not at-risk, its relationship with different, but
      related, constructs and its ability to predict suicide ideation.

PMID- 30216130
TI  - Direct Posterior Restorations: A 13-Year Survey of Teaching Trends and Use of
      Materials.
AB  - OBJECTIVE:: The study aimed to evaluate teaching trends and use of materials in
      direct posterior restorations during a 13-year period in an Israeli dental
      school. METHODS:: Data registered in computerized files, relating to posterior
      restorations performed in the student clinic during the past 13 years (2004
      2016), were collected. The restorative materials used (ie, amalgam vs composite),
      the type of tooth, and the number of surfaces restored were analyzed. RESULTS::
      Data analysis included 26,925 restorations performed during 13 years. The number
      of one-surface composite restorations increased from 54.7% (n=330) to 81.9%
      (n=873). Two-surface restorations increased from 33.3% (n=254) to 64.3% (n=721).
      The percentage of amalgam restorations in three-surface restorations decreased
      from 72.08% to 51.34% (n=173). Analysis of tooth type showed that in 2016, the
      number of composite restorations performed in premolars reached 80.87% (n=723)
      and in molars 63.50% (n=1035). The percentage of composite restorations in the
      mandible and the maxilla was virtually equal. CONCLUSIONS:: A clear trend in
      favor of composite resin restorations is evident in the 13-year survey and
      suggests a move toward an amalgam-free era.

PMID- 30216124
TI  - Guideline for the Management of Clostridium Difficile Infection in Children and
      Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation
      Recipients.
AB  - Purpose The aim of this work was to develop a clinical practice guideline for the
      prevention and treatment of Clostridium difficile infection (CDI) in children and
      adolescents with cancer and pediatric hematopoietic stem-cell transplantation
      (HSCT) patients. Methods An international multidisciplinary panel of experts in
      pediatric oncology and infectious diseases with patient advocate representation
      was convened. We performed systematic reviews of randomized controlled trials for
      the prevention or treatment of CDI in any population and considered the
      directness of the evidence to children with cancer and pediatric HSCT patients.
      We used the Grading of Recommendations Assessment, Development, and Evaluation
      approach to generate recommendations. Results The panel made strong
      recommendations to administer either oral metronidazole or oral vancomycin for
      the initial treatment of nonsevere CDI and oral vancomycin for the initial
      treatment of severe CDI. Fidaxomicin may be considered in the setting of
      recurrent CDI. The panel suggested that probiotics not be routinely used for the
      prevention of CDI, and that monoclonal antibodies and probiotics not be routinely
      used for the treatment of CDI. A strong recommendation to not use fecal
      microbiota transplantation was made in this population. We identified key
      knowledge gaps and suggested directions for future research. Conclusion We
      present a guideline for the prevention and treatment of CDI in children and
      adolescents with cancer and pediatric HSCT patients. Future research should
      include randomized controlled trials that involve children with cancer and
      pediatric HSCT patients to improve the management of CDI in this population.

PMID- 30216133
TI  - Could Eggs Help Increase Dietary Protein Intake in Older Adults? - Exploring
      Reasons for the Consumption and Non-Consumption of Eggs in People over 55 years
      old.
AB  - Compared to other protein-rich foods, eggs are of soft texture, easy to cook, and
      low cost, and may be useful in increasing protein intakes in older adults. Focus
      groups and interviews were used to explore all reasons for consuming and not
      consuming eggs in older adults. Forty-two individuals (20 males, 22 females, aged
      56-96 years) took part in one of eight focus groups or two individual interviews.
      Thematic analyses revealed 69 different reasons for eating or not eating eggs in
      this population. Reasons were related to: hedonics, properties of the food,
      preparation style, convenience, physical environment, variety, physical
      health/abilities, nutrition and health knowledge, food safety, social
      environment, morality, emotion, and habit. Some of these reasons are likely to be
      specific to egg consumption in older adults, e.g. properties of the food and
      convenience combined with physical health/abilities. Some reasons are also likely
      to be more relevant to older than younger individuals, e.g. medical factors.
      Investigation of the reasons most related to intake on a population-wide scale
      would aid the development of interventions.

PMID- 30216134
TI  - Addressing the measurement challenge in elder abuse interventions: need for a
      severity framework.
AB  - The field of elder abuse is evolving toward an emphasis on intervention research.
      However, researchers currently rely on binary approaches to measure elder abuse
      phenomena, which fail to capture changes in problem status over the course of
      intervention. This commentary develops a case for severity as a framework to
      operationalize and measure elder abuse in intervention research and practice. A
      severity framework provides enhanced elder abuse measurement responsiveness and
      aligns with the dominant client-centered, harm-reduction clinical approach to
      intervening with elder abuse cases.

PMID- 30216136
TI  - SALT STRESS IN THE RENAL TUBULES IS LINKED TO TAL SPECIFIC EXPRESSION OF
      UROMODULIN AND AN UPREGULATION OF HEAT SHOCK GENES.
AB  - Previously, our comprehensive cardiovascular characterisation study validated
      Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively
      synthesised at the thick ascending limb of the loop of Henle and is encoded by
      the Umod gene. Umod-/- mice have significantly lower blood pressure than Umod+/+
      mice, are resistant to salt-induced changes in blood pressure, and show a
      leftward shift in pressure-natriuresis curves reflecting changes of sodium
      reabsorption. Salt stress triggers transcription factors and genes that alter
      renal sodium reabsorption. To date there are no studies on renal transcriptome
      responses to salt stress. Here we aimed to delineate salt stress pathways in
      tubules isolated from Umod+/+ mice (a model of sodium retention) and Umod-/- mice
      (a model of sodium depletion) +/-300mOsmol sodium chloride (n=3 per group)
      performing RNA-Seq. In response to salt stress, the tubules of Umod+/+ mice
      displayed an up regulation of heat shock transcripts. The greatest changes
      occurred in the expression of: Hspa1a (Log2 fold change 4.35, p=2.48e-12) and
      Hspa1b (Log2 fold change 4.05, p=2.48e-12). This response was absent in tubules
      of Umod-/- mice. Interestingly, 7 of the genes discordantly expressed in the Umod
      /- tubules were electrolyte transporters. Our results are the first to show that
      salt stress in renal tubules alters the transcriptome, increasing the expression
      of heat shock genes. This direction of effect in Umod+/+ tubules suggest the
      difference is due to the presence of Umod facilitating greater sodium entry into
      the tubule cell reflecting a specific response to salt stress.

PMID- 30216135
TI  - Understanding work enjoyment among older workers: The significance of flexible
      work options and age discrimination in the workplace.
AB  - Although the number of older workers in the U.S. is increasing, there is a gap in
      knowledge on whether or not they actually enjoy working. This study, based on a
      conceptual framework focusing on job resources and demands, explored likely
      workplace determinants of work enjoyment among older workers aged 50 or over.
      Using the 2012 wave of the Health and Retirement Study, a partial proportional
      odds model was used to detect determinants of work enjoyment. Results showed that
      higher levels of work enjoyment were significantly and negatively associated with
      the level of perceived retirement pressure and promotion preference for younger
      workers, and positively associated with moving to less demanding positions. Self
      employment showed a noticeable enhancement of work enjoyment. This study
      highlights the significance of flexible work options and age discrimination in
      the workplace in understanding work enjoyment later in life.

PMID- 30216137
TI  - Grief severity: A comparison between human and companion animal death.
AB  - Grief severity was investigated and compared amongst 50 participants aged 18 to
      65 years who had experienced the death of a human (n = 35) or the death of a
      companion animal (n = 15). Participants were recruited in Australia and completed
      an on-line self-report questionnaire package, measuring grief severity, social
      support, and emotional connection to the deceased. There were no significant
      differences between the levels of grief severity, however, the qualitative
      analyses highlighted the complexities associated with attempting to compare these
      grief experiences. These results highlight the importance of therapists
      acknowledging and validating companion animal grief.

PMID- 30216138
TI  - The Effect of Organized Versus Supervised Recess on Elementary School Children's
      Participation, Physical Activity, Play, and Social Behavior: A Cluster Randomized
      Controlled Trial.
AB  - BACKGROUND: Recess strategies that increase children's physical activity and
      contribute to the daily 60 minutes of moderate to vigorous physical activity
      (MVPA) are recommended. METHODS: A cluster randomized trial was conducted to
      examine the effect of supervised versus organized recess on children's
      participation, physical activity, play, and social behavior. In supervised
      recess, children were free to play, and physical education (PE) teachers ensured
      safety. In organized recess, PE teachers provided challenging tasks. Data were
      collected using systematic observation. Children (N = 281; 8-10 y) from 14
      schools received a 6-day parkour unit in PE and three opportunities to
      participate in a 20-minute parkour recess. Schools were randomized over a
      supervised and organized parkour recess condition. RESULTS: The majority of
      children participated in parkour recess (range = 56%-85%), with more boys
      participating in all 3 organized versus supervised recess sessions (57% vs 35%, P
      = .01). Boys spent more time in MVPA during organized recess (79% vs 71%, P =
      .02). Boys and girls spent more time in activity games during organized recess
      (59% vs 46%, P = .01; 59% vs 47%, P = .001). CONCLUSION: Organized recess
      attracted more children and made the largest contribution to daily MVPA.

PMID- 30216139
TI  - Circuit Polarity Effect of Cortical Connectivity, Activity, and Memory.
AB  - Experimental constraints have traditionally implied separate studies of different
      cortical functions, such as memory and sensory-motor control. Yet certain
      cortical modalities, while repeatedly observed and reported, have not been
      clearly identified with one cortical function or another. Specifically, while
      neuronal membrane and synapse polarities with respect to a certain potential
      value have been attracting considerable interest in recent years, the purposes of
      such polarities have largely remained a subject for speculation and debate.
      Formally identifying these polarities as on-off neuronal polarity gates, we
      analytically show that cortical circuit structure, behavior, and memory are all
      governed by the combined potent effect of these gates, which we collectively term
      circuit polarity. Employing widely accepted and biologically validated firing
      rate and plasticity paradigms, we show that circuit polarity is mathematically
      embedded in the corresponding models. Moreover, we show that the firing rate
      dynamics implied by these models are driven by ongoing circuit polarity gating
      dynamics. Furthermore, circuit polarity is shown to segregate cortical circuits
      into internally synchronous, externally asynchronous subcircuits, defining their
      firing rate modes in accordance with different cortical tasks. In contrast to the
      Hebbian paradigm, which is shown to be susceptible to mutual neuronal
      interference in the face of asynchrony, circuit polarity is shown to block such
      interference. Noting convergence of synaptic weights, we show that circuit
      polarity holds the key to cortical memory, having a segregated capacity linear in
      the number of neurons. While memory concealment is implied by complete neuronal
      silencing, memory is restored by reactivating the original circuit polarity.
      Finally, we show that incomplete deterioration or restoration of circuit polarity
      results in memory modification, which may be associated with partial or false
      recall, or novel innovation.

PMID- 30216140
TI  - Robust Closed-Loop Control of a Cursor in a Person with Tetraplegia using
      Gaussian Process Regression.
AB  - Intracortical brain computer interfaces can enable individuals with paralysis to
      control external devices through voluntarily modulated brain activity. Decoding
      quality has been previously shown to degrade with signal nonstationarities
      specifically, the changes in the statistics of the data between training and
      testing data sets. This includes changes to the neural tuning profiles and
      baseline shifts in firing rates of recorded neurons, as well as nonphysiological
      noise. While progress has been made toward providing long-term user control via
      decoder recalibration, relatively little work has been dedicated to making the
      decoding algorithm more resilient to signal nonstationarities. Here, we describe
      how principled kernel selection with gaussian process regression can be used
      within a Bayesian filtering framework to mitigate the effects of commonly
      encountered nonstationarities. Given a supervised training set of (neural
      features, intention to move in a direction)-pairs, we use gaussian process
      regression to predict the intention given the neural data. We apply kernel
      embedding for each neural feature with the standard radial basis function. The
      multiple kernels are then summed together across each neural dimension, which
      allows the kernel to effectively ignore large differences that occur only in a
      single feature. The summed kernel is used for real-time predictions of the
      posterior mean and variance under a gaussian process framework. The predictions
      are then filtered using the discriminative Kalman filter to produce an estimate
      of the neural intention given the history of neural data. We refer to the
      multiple kernel approach combined with the discriminative Kalman filter as the MK
      DKF. We found that the MK-DKF decoder was more resilient to nonstationarities
      frequently encountered in-real world settings yet provided similar performance to
      the currently used Kalman decoder. These results demonstrate a method by which
      neural decoding can be made more resistant to nonstationarities.

PMID- 30216141
TI  - Unconscious Biases in Neural Populations Coding Multiple Stimuli.
AB  - Throughout the nervous system, information is commonly coded in activity
      distributed over populations of neurons. In idealized situations where a single,
      continuous stimulus is encoded in a homogeneous population code, the value of the
      encoded stimulus can be read out without bias. However, in many situations,
      multiple stimuli are simultaneously present; for example, multiple motion
      patterns might overlap. Here we find that when multiple stimuli that overlap in
      their neural representation are simultaneously encoded in the population, biases
      in the read-out emerge. Although the bias disappears in the absence of noise, the
      bias is remarkably persistent at low noise levels. The bias can be reduced by
      competitive encoding schemes or by employing complex decoders. To study the
      origin of the bias, we develop a novel general framework based on gaussian
      processes that allows an accurate calculation of the estimate distributions of
      maximum likelihood decoders, and reveals that the distribution of estimates is
      bimodal for overlapping stimuli. The results have implications for neural coding
      and behavioral experiments on, for instance, overlapping motion patterns.

PMID- 30216142
TI  - Cross-Entropy Pruning for Compressing Convolutional Neural Networks.
AB  - The success of CNNs is accompanied by deep models and heavy storage costs. For
      compressing CNNs, we propose an efficient and robust pruning approach, cross
      entropy pruning (CEP). Given a trained CNN model, connections were divided into
      groups in a group-wise way according to their corresponding output neurons. All
      connections with their cross-entropy errors below a grouping threshold were then
      removed. A sparse model was obtained and the number of parameters in the baseline
      model significantly reduced. This letter also presents a highest cross-entropy
      pruning (HCEP) method that keeps a small portion of weights with the highest CEP.
      This method further improves the accuracy of CEP. To validate CEP, we conducted
      the experiments on low redundant networks that are hard to compress. For the
      MNIST data set, CEP achieves an 0.08% accuracy drop required by LeNet-5 benchmark
      with only 16% of original parameters. Our proposed CEP also reduces approximately
      75% of the storage cost of AlexNet on the ILSVRC 2012 data set, increasing the
      top-1 errorby only 0.4% and top-5 error by only 0.2%. Compared with three
      existing methods on LeNet-5, our proposed CEP and HCEP perform significantly
      better than the existing methods in terms of the accuracy and stability. Some
      computer vision tasks on CNNs such as object detection and style transfer can be
      computed in a high-performance way using our CEP and HCEP strategies.

PMID- 30216143
TI  - Tensor Representation of Topographically Organized Semantic Spaces.
AB  - Human brains seem to represent categories of objects and actions as locations in
      a continuous semantic space across the cortical surface that reflects the
      similarity among categories. This vision of the semantic organization of
      information in the brain, suggested by recent experimental findings, is in
      harmony with the well-known topographically organized somatotopic, retinotopic,
      and tonotopic maps in the cerebral cortex. Here we show that these topographies
      can be operationally represented with context-dependent associative memories. In
      these models, the input vectors and, eventually also, the associated output
      vectors are multiplied by context vectors via the Kronecker tensor product, which
      allows a spatial organization of memories. Input and output tensor contexts
      localize matrices of semantic categories into a neural layer or slice and, at the
      same time, direct the flow of information arriving at the layer to a specific
      address, and then forward the output information toward the corresponding
      targets. Given a neural topographic pattern, the tensor representation will place
      a set of associative matrix memories within a topographic regionalized host
      matrix in such way that they reproduce the empirical pattern of patches in the
      actual neural layer. Progressive approximations to this goal are accomplished by
      avoiding excessive overlap of memories or the existence of empty regions within
      the host matrix.

PMID- 30216145
TI  - Adaptive Gaussian Process Approximation for Bayesian Inference with Expensive
      Likelihood Functions.
AB  - We consider Bayesian inference problems with computationally intensive likelihood
      functions. We propose a Gaussian process (GP)-based method to approximate the
      joint distribution of the unknown parameters and the data, built on recent work
      (Kandasamy, Schneider, & Poczos, 2015). In particular, we write the joint density
      approximately as a product of an approximate posterior density and an
      exponentiated GP surrogate. We then provide an adaptive algorithm to construct
      such an approximation, where an active learning method is used to choose the
      design points. With numerical examples, we illustrate that the proposed method
      has competitive performance against existing approaches for Bayesian computation.

PMID- 30216144
TI  - Applications of Recurrent Neural Networks in Environmental Factor Forecasting: A
      Review.
AB  - Analysis and forecasting of sequential data, key problems in various domains of
      engineering and science, have attracted the attention of many researchers from
      different communities. When predicting the future probability of events using
      time series, recurrent neural networks (RNNs) are an effective tool that have the
      learning ability of feedforward neural networks and expand their expression
      ability using dynamic equations. Moreover, RNNs are able to model several
      computational structures. Researchers have developed various RNNs with different
      architectures and topologies. To summarize the work of RNNs in forecasting and
      provide guidelines for modeling and novel applications in future studies, this
      review focuses on applications of RNNs for time series forecasting in
      environmental factor forecasting. We present the structure, processing flow, and
      advantages of RNNs and analyze the applications of various RNNs in time series
      forecasting. In addition, we discuss limitations and challenges of applications
      based on RNNs and future research directions. Finally, we summarize applications
      of RNNs in forecasting.

PMID- 30216148
TI  - Excess Deaths Associated With Underweight, Overweight, and Obesity: An Evaluation
      of Potential Bias.
AB  - As the prevalence of obesity has increased over time in the United States (1,2),
      concern over the association between body weight and excess mortality also
      increased. In 2005, an analysis of estimated excess deaths, relative to the
      normal weight category (body mass index [BMI] 18.5-24.9), that were associated
      with underweight (BMI less than 18.5), overweight (BMI 25.0-29.9), and obesity
      (BMI greater than or equal to 30) in U.S. adults in 2000 was published (3). Both
      underweight and obesity, particularly higher levels of obesity, were associated
      with increased mortality relative to the normal weight category. Obesity was
      estimated to be associated with 111,909 excess deaths (95% confidence interval
      [CI]: 53,754 to 170,064) in 2000 relative to the normal weight category, and
      underweight with 33,746 excess deaths (95% CI: 15,726 to 51,766). Overweight was
      associated with reduced mortality (-86,094 deaths; 95% CI: -161,223 to -10,966).
      This report evaluates several potential sources of bias in that analysis.

PMID- 30216146
TI  - The first complete genomic structure of Butyrivibrio fibrisolvens and its
      chromid.
AB  - Butyrivibrio fibrisolvens forms part of the gastrointestinal microbiome of
      ruminants and other mammals, including humans. Indeed, it is one of the most
      common bacteria found in the rumen and plays an important role in ruminal
      fermentation of polysaccharides, yet, to date, there is no closed reference
      genome published for this species in any ruminant animal. We successfully
      assembled the nearly complete genome sequence of B. fibrisolvens strain INBov1
      isolated from cow rumen using Illumina paired-end reads, 454 Roche single-end and
      mate pair sequencing technology. Additionally, we constructed an optical
      restriction map of this strain to aid in scaffold ordering and positioning, and
      completed the first genomic structure of this species. Moreover, we identified
      and assembled the first chromid of this species (pINBov266). The INBov1 genome
      encodes a large set of genes involved in the cellulolytic process but lacks key
      genes. This seems to indicate that B. fibrisolvens plays an important role in
      ruminal cellulolytic processes, but does not have autonomous cellulolytic
      capacity. When searching for genes involved in the biohydrogenation of
      unsaturated fatty acids, no linoleate isomerase gene was found in this strain.
      INBov1 does encode oleate hydratase genes known to participate in the
      hydrogenation of oleic acids. Furthermore, INBov1 contains an enolase gene, which
      has been recently determined to participate in the synthesis of conjugated
      linoleic acids. This work confirms the presence of a novel chromid in B.
      fibrisolvens and provides a new potential reference genome sequence for this
      species, providing new insight into its role in biohydrogenation and carbohydrate
      degradation.

PMID- 30216147
TI  - Genome-based transmission modelling separates imported tuberculosis from recent
      transmission within an immigrant population.
AB  - In many countries the incidence of tuberculosis (TB) is low and is largely shaped
      by immigrant populations from high-burden countries. This is the case in Norway,
      where more than 80 % of TB cases are found among immigrants from high-incidence
      countries. A variable latent period, low rates of evolution and structured social
      networks make separating import from within-border transmission a major conundrum
      to TB control efforts in many low-incidence countries. Clinical Mycobacterium
      tuberculosis isolates belonging to an unusually large genotype cluster associated
      with people born in the Horn of Africa have been identified in Norway over the
      last two decades. We modelled transmission based on whole-genome sequence data to
      estimate infection times for individual patients. By contrasting these estimates
      with time of arrival in Norway, we estimate on a case-by-case basis whether
      patients were likely to have been infected before or after arrival. Independent
      import was responsible for the majority of cases, but we estimate that about one
      quarter of the patients had contracted TB in Norway. This study illuminates the
      transmission dynamics within an immigrant community. Our approach is broadly
      applicable to many settings where TB control programmes can benefit from
      understanding when and where patients acquired TB.

PMID- 30216149
TI  - Guideline Clearinghouse Is Dead. Long Live the Guideline Clearinghouse?
AB  - The National Guidelines Clearinghouse might be making a comeback. It's been
      contracted out to the ECRI Institute, a not-for-profit organization that conducts
      medical safety research. ECRI plans to have a version of the clearinghouse
      website up and running anytime soon, with plans for a full relaunch in 2019.

PMID- 30216150
TI  - With CMS Demanding More Accountability in the MSSP, Will It Be 'ACOs Overboard'?
AB  - For 169 ACOs, time is up to take on downside risk. This group-30% of all of those
      in the Medicare Shared Savings Program (MSSP)-are Track 1, upside risk-only ACOs
      and are nearing the end of their contracts with CMS.

PMID- 30216151
TI  - Dupixent, a New Entrant In the Asthma Lists.
AB  - Sanofi and Regeneron's Dupixent (dupilumab)-which is already approved for atopic
      dermatitis-has an FDA action date of October 20 for its asthma indication. It
      will join Nucala, (mepolizumab), Cinqair (reslizumab), and Fasenra (benralizumab)
      as a monoclonal antibody approved as a treatment for the type 2 inflammation
      phenotype in severe asthma.

PMID- 30216152
TI  - Backlash Against Copay Accumulators.
AB  - With accumulators, the value of any copay assistance cards or coupons does not
      count toward out-of-pocket medicine costs that are applied toward deductibles.
      It's a cost-shifting tool that's facing pushback from patients, providers, and
      others saying that accumulators will hurt public health.

PMID- 30216153
TI  - Health Care Quality: It's Motherhood and Apple Pie. Until You Start To Measure
      It.
AB  - : The pay-for-value movement could justify rewarding-and punishing-doctors based
      on quality scores. PROBLEM: Hardly anyone likes the current ways quality is
      measured, especially physicians. Few believe that Medicare's Merit-based
      Incentive Payment System (MIPS) will clear things up. In fact, it might cause
      more confusion.

PMID- 30216154
TI  - Hey, Big Spender! Why Does Your Quality Lag So Far Behind Other Countries?
AB  - The United States is the world's biggest spender on health care by far. And what
      do we get for it? Not as much as we should. Our quality shortcomings are not for
      lack of knowledge: Stakeholders know what to do to close these gaps. So why
      aren't they doing it?

PMID- 30216155
TI  - Have a Date With Surgery? PROMs Help Patients Decide.
AB  - Patient-reported outcomes measures (PROMs) use a patient's response to questions
      to measure health status. If they're going to catch on payers will need to
      incentivize use. So far, that's not happening. But clinicians who use PROMs for
      clinical decision making might be providing a valuable service.

PMID- 30216156
TI  - Nurse Practitioners to Docs, Lawmakers: Give Us Our Independence.
AB  - And that means full scope of practice as primary care providers. Medical
      societies hate the idea and think that nurse practitioners need to be tethered
      securely to a physician office in order to ensure top-notch care. Nurse
      practitioners counter that they can help shore up primary care.

PMID- 30216157
TI  - The Opaque Fight Against Price Transparency.
AB  - For those who doubt the importance of transparency in price and quality to free
      the market, you just have to look behind the public curtain and observe the
      fierceness with which the opponents of transparency are trying to keep consumers
      in the dark.

PMID- 30216158
TI  - Care Variation Reduction Going Nowhere? Used Strategically, a HEIP Might Help.
AB  - HEIP stands for hospital efficiency improvement program. It is a legal contract
      outlining specific initiatives where physician-driven variance can be improved
      across specialties and departments. For organizations with a good strategy to
      reduce care variation, a HEIP can provide the jolt of incentive that generates
      real improvement.

PMID- 30216159
TI  - How a 'Waste-Free Formulary' Misses What's Most Important to Employers.
AB  - The "waste-free formulary" under development by the Pacific Business Group on
      Health sounds promising, but ultimately may not deliver the impact to self
      insured employers its creators are promising. The approach glosses over a
      critical question: What constitutes "high-value"? The definition of value plays a
      central role in determining the care that patients ultimately receive.

PMID- 30216160
TI  - Pharma APMs: Can the Industry Learn To Play Well With Others?
AB  - The alternative payment model (APM) is a nontraditional financial arrangement
      that rewards health care providers who deliver cost-effective, high-quality care.
      Now we are facing the possibility that pharmaceutical manufacturers and insurers
      will embrace APMs as a payment mechanism in some situations.

PMID- 30216161
TI  - Effects of prior abdominal surgery on laparoscopic cholecystectomy.
AB  - OBJECTIVES: With increased experience and technological advancement, laparoscopic
      cholecystectomy is reported to be safe and feasible even in the presence of most
      of the previously recognized contraindications. The purpose of this study was to
      explore the effects of prior upper and lower abdominal surgery on laparoscopic
      cholecystectomy. MATERIAL AND METHODS: A retrospective evaluation of all
      sequential patients who underwent laparoscopic cholecystectomy from January 2014
      to June 2016 was conducted. Patients were divided into three groups (Group A:
      patients without any prior abdominal surgical procedures; Group B: patients with
      prior upper abdominal surgical procedures; and Group C: patients with prior lower
      abdominal surgical procedures). RESULTS: A total of 329 patients were assessed.
      Group A consisted of 223, Group B of 18, and Group C of 88 patients. A
      statistically significantly higher operative time, postoperative pain, and
      complication rate after laparoscopic cholecystectomy were noted in patients with
      prior upper abdominal surgery. The groups were comparable regarding patients'
      demographics and surgery indications. The length of hospital stay was not
      statistically different between the groups (p=0.065). CONCLUSION: According to
      the results of the current study, prior upper abdominal surgery leads to a
      significantly longer procedure time, higher postoperative pain, and complication
      rates after laparoscopic cholecystectomy. However, the length of hospital stay
      was not affected by the parameters investigated.

PMID- 30216162
TI  - Comparison of limberg flap and oval flap techniques in sacrococcygeal pilonidal
      sinus disease surgery.
AB  - OBJECTIVES: Although many surgical techniques have been described for treatment
      of pilonidal sinus disease (PSD), the ideal treatment method remains
      controversial. The purpose of this study was to compare Limberg flap and oval
      flap techniques in patients with PSD. MATERIAL AND METHODS: Patients diagnosed
      with PSD who underwent surgery using either the Limberg flap or oval flap
      technique between January 2012 and January 2016 at the general surgery outpatient
      clinic were retrospectively reviewed from the database of our hospital; 142
      patients (124 males and 18 females) were invited for examination. The demographic
      characteristics of the patients such as age and gender, hospital stays, seroma
      occurrence, surgical site infections, wound dehiscence, flap necrosis, loss of
      sensation, and recurrences were evaluated based on the information obtained from
      the database and from physical examinations as well as questioning of the
      patients. The results were statistically compared, and a p value of <0.05 was
      considered significant. RESULTS: The mean age of the patients was 27.5+/-7.8
      years in the Limberg flap group and 26.5+/-7.2 years in the oval flap group. No
      significant difference was found between the two groups regarding patients' mean
      age; gender distribution; postoperative hospital stay; recurrence; and
      complications, such as seroma, infection, wound dehiscence, and loss of
      sensation. Flap necrosis was not observed in any of the patients. CONCLUSION: The
      Limberg flap and oval flap procedures both involve minimum morbidity and short
      hospital stay because they were not superior to one another regarding treatment
      effectiveness, complications, and recurrence in the pilonidal sinus surgery.

PMID- 30216163
TI  - Recurrent intestinal ischemia related to Behcet's Disease.
AB  - Behcet's disease is a systemic inflammatory disease that may affect multiple
      organs. However, intraabdominal complications requiring surgical intervention are
      rare in the natural course of the disease. A 32-year-old male patient with
      Behcet's disease who had been followed for 5 years with a diagnosis of acute
      abdominal syndrome was operated on twice in 18 days. Intestinal ischemia was
      identified in different segments of the jejenum during each operation. Recurrent
      segmental intestinal ischemia within a short time interval is rare, although the
      gastrointestinal involvement can be seen in the normal course of Behcet's
      disease.

PMID- 30216164
TI  - Coexistence of low-grade mucinous neoplasm and carcinoid (collision tumor) within
      multiple appendiceal diverticula: A case report.
AB  - Neoplasms of the appendix are very rare. They usually show glandular or
      neuroendocrine differentiation, and when they both occur in the same area, it is
      called a "collision tumor." Low-grade mucinous neoplasms associated with
      appendiceal diverticula are also uncommon. The appendectomy specimen of a 60-year
      old man contained dense and mucoid luminal content on the distal tip, and
      similarly a solid, yellow, lumen-obscuring tumor with a diameter of 1.5 cm at the
      base of the appendix was detected. Microscopically, there were three diverticula
      that comprised herniation of the mucosal layer through the appendiceal wall.
      Interestingly, all of the diverticula and the normal-appearing appendiceal wall
      were lined by adenomatous epithelium. The luminal portion had pools of mucin
      containing, rare clusters of low-grade epithelium that gave rise to the diagnosis
      of a "low-grade mucinous neoplasm." The solid-appearing tumor was diagnosed as a
      "neuroendocrine neoplasm," and there was no transition zone between these two
      types of tumors. There are some cases that have been reported as low-grade
      mucinous neoplasms associated with appendicular diverticula and collision tumors
      consisting both mucinous neoplasms and carcinoid tumors in the literature; our
      case has a unique appearance with two different types of tumors both in the
      appendix wall and within multiple diverticula.

PMID- 30216165
TI  - Obesity and Bariatric Surgery awareness in the Kocaeli province, a leading
      industrial city in Turkey.
AB  - OBJECTIVES: An increase in the prevelance of obesity is a worldwide problem. It
      many serious health problems, especially cardiovascular diseases and type-2
      diabetes mellitus. Conservative therapies such as diet modification and exercise
      are the most preferable obesity treatments. Bariatric surgery is the most
      appropriate treatment in suitable patients. Several studies showed that a very
      low number of patients prefer bariatric surgery even though it would be
      appropriate. This study aimed to assess and raise awareness about the obesity
      level, its complications, and treatment methods, especially bariatric surgery
      among obese patients in Kocaeli, which is one of the most socio-economically
      developed cities, as well as the leading industrial city in Turkey. MATERIAL AND
      METHODS: A survey was designed to assess the knowledge about obesity, its
      complications, and bariatric surgery in the Kocaeli province. It was administered
      to 232 adult patients with a body mass index greater than 30 in different
      outpatient clinics where patients suffering obesity were treated. RESULTS: It has
      been seen that although the contribution factors and complications of obesity are
      well known, awareness of the body mass index was insufficient. Most of patients
      have tried to lose weight at least once and most patients have heard of bariatric
      surgery before. However, the details were not well known. The gastric band method
      is the most known method, and the most known risk of surgery was death. The main
      source of knowledge about bariatric surgery was television. The increasing body
      mass index affects patients' attitudes toward the surgery positively. CONCLUSION:
      Knowledge of bariatric surgery is inadequate in the Kocaeli province, which is
      one of the most socio-economically developed cities, as well as the leading
      industrial city in Turkey. More social responsibility projects and more objective
      elucidating via television and social media are also needed to increase the
      awareness of bariatric surgery.

PMID- 30216166
TI  - Surgery for Intestinal Crohn's Disease: Results of a multidisciplinary approach.
AB  - OBJECTIVES: Crohn's disease is a chronic inflammatory bowel disease that requires
      lifelong multidisciplinary management. Seventy percent of patients affected by
      Crohn's disease will require at least one surgical procedure over their lifetime.
      The aim of this retrospective study was to present our series of patients
      suffering from Crohn's disease who were scheduled for surgery by a
      multidisciplinary team. MATERIAL AND METHODS: The data were retrieved from a
      review of 950 patients with Crohn's disease treated at our institution between
      March 2000 and March 2016. Only patients with intestinal Crohn's disease were
      included into the study. A multidisciplinary team assessed the decision to
      perform surgery. RESULTS: There were 203 patients who underwent surgery included
      in this study. One hundred and sixty-six were intestinal and 37 were perianal
      Crohn's disease. The mean age was 36+/-11.5 (range, 12-75) years. Ninety-two were
      stricturing, 45 were fistulizing, and 12 were inflammatory. The most commonly
      affected site was the ileocecal region (n=109, 65.7%), and the most common
      surgical procedure was the ileocecal resection (n=109, 65.6%). Laparoscopic
      approach was the procedure of choice in 56 (33.7%) patients. Of the patients
      enrolled, the most common early (<30 days) complications observed were the wound
      infection as the first (n=11) and anastomotic leak as the second (n=10). The
      mortality rate was 2.4% (n=4). CONCLUSION: Multidisciplinary approach to Crohn's
      disease may decrease the surgical complications and recurrence rates leading to a
      better treatment.

PMID- 30216167
TI  - Comparison of the non-mortal gunshot and handmade explosive blast traumas during
      a low-intensity conflict on urban terrain.
AB  - OBJECTIVES: We aimed to conduct a cross-sectional data analysis involving 60
      patients wounded during a low-intensity conflict on urban terrain. MATERIAL AND
      METHODS: Data of the 60 patients wounded during a low-intensity conflict on urban
      terrain between September 1st, 2016, and January 15th, 2017, and transferred to
      our hospital after the initial medical interventions conducted in the regional
      hospitals were probed retrospectively. Group A consisted of 25 (41.67%) patients
      suffering gunshot wounds, and Group B consisted of 35 (58.33%) patients with
      blast trauma injuries. Their Abbreviated Injury Scale scores were compared
      according to the injured body compartment. RESULTS: In both groups, extremities
      were the most common site of injury (17 [50%] for Group A, 18 [33.33%] for Group
      B). The difference between the two groups was statistically significant for only
      head and neck injuries and facial injuries (p<0.05). In each group, only one body
      compartment was affected in 19 patients, which represented 55.88% of patients in
      Group A and 35.18% of patients in Group B. Injuries of three compartments
      concurrently occurred in 3 (8.82%) patients in Group A and 4 (7.4%) patients in
      Group B. None of our patients died because of their injuries. CONCLUSION:
      Contrary to the expected, gunshot casualties were found to be more likely to
      suffer from extremity injuries than blast casualties did, and it should be noted
      that blast trauma casualties tend to have multiple compartment injuries that
      should not be missed. Ocular ruptures are also common, especially with blast
      injuries, warranting equipping the personnel with protective goggles.

PMID- 30216169
TI  - Incidental giant adrenal lymphangioma presenting as nonfunctional cystic mass.
AB  - Surrenal masses can be encountered with many different clinical manifestations
      and a diverse spectrum of etiologies in clinical practice. Recent advances in
      imaging and laboratory studies as well as their increasingly widespread use and
      easy accessibility have currently made it possible to diagnose a greater number
      of surrenal masses than ever. The basic approach principles vary for incidentally
      detected masses, benign/malignant masses, and hormonoactive masses. Lymphangiomas
      are benign congenital malformations of lymphatic channels that primarily affect
      the neck and head region. They are typically found in children younger than 2
      years of age, they are uncommon in adults, and they rarely involve surrenal
      glands. In this paper, we present a woman with a hormonally inactive right giant
      surrenal mass showing recent rapid growth, which was diagnosed to be a
      lymphangioma with an atypical localization in the histopathological examination.
      The patient was operated with right surrenalectomy and total mass excision via
      laparoscopic lateral transperitoneal approach.

PMID- 30216168
TI  - Management of iatrogenic bile duct injuries: Multiple logistic regression
      analysis of predictive factors affecting morbidity and mortality.
AB  - OBJECTIVE: Iatrogenic bile duct injuries remain a challenge for the surgeons to
      overcome. The predictive factors affecting morbidity and mortality are important
      for determining the best management modality. MATERIALS AND METHODS: The patients
      who referred to Ege University Faculty of Medicine after laparoscopy associated
      iatrogenic bile duct injury are grouped according to Strasberg-Bismuth
      classification system. The type and number of prior attempts, concomitant
      complications, and treatment modalities are analyzed using the SPSS version 18
      (IBM, Chicago, IL, USA). The variables with p<0.10 were considered for univariate
      analysis and then evaluated for predictive factors by forward Logistic Regression
      method using multiple logistic regression analysis. RESULTS: According to the
      analysis of 105 patients who were referred during 2004-2014, the type and number
      of prior attempts are considered predictive factors in sepsis. In multiple
      logistic regression analysis, abscess formation, concomitant vascular injury, and
      serum bilirubin level are significantly effective in predicting mortality.
      CONCLUSION: The management of iatrogenic bile duct injuries should be carefully
      planned with a multidisciplinary approach. The predictive factors affecting
      morbidity and mortality are important in determining the best modality for
      managing iatrogenic bile duct injuries. Abscess formation, vascular injury, and
      serum bilirubin level are the potential risk factors. Therefore, we can strongly
      recommend immediate assessment of patients for prompt diagnosis and referring to
      an HPB center, to avoid further injuries.

PMID- 30216170
TI  - Laparoscopic partial cecum resection in appendix intussusception.
AB  - Appendix intussusception (AI) is a difficult disease to diagnose. Various
      features of the disease have been analyzed in a 35-year-old female patient who
      was admitted with abdominal pain and diagnosed with AI. The diagnosis was made
      with colonoscopy and abdominal computed tomography. Laparoscopic partial cecum
      resection was performed. The pathology examination revealed foci of endometriosis
      externa, which infiltrated the muscular layer of the appendix. AI should be kept
      in mind in the differential diagnosis of recurrent abdominal pain. Colonoscopy is
      an indispensable examination for the differential diagnosis. Laparoscopic partial
      cecum resection, preserving ileocecal valve, is an appropriate treatment approach
      in irreducible cases that are not suspected to be malignant.

PMID- 30216171
TI  - Roux-en-Y fistulojejunostomy in the management of persistent external pancreatic
      fistula: Is it olde worlde?
AB  - OBJECTIVE: This article aims to identify the patient selection criteria and
      approach in treating persistent external pancreatic fistulas surgically with Roux
      en-Y fistulojejunostomy, and it evaluates the outcomes of Roux-en-Y
      fistulojejunostomy with a review of the relevant literature. MATERIAL AND
      METHODS: A retrospective data analysis from January 2010 to May 2017 revealed 6
      patients who were managed with Roux-en-Y fistulojejunostomy for persistent
      external pancreatic fistulas, and their details were entered in a proforma.
      Standard surgical steps were performed in all patients, and the patients were
      followed up postoperatively for 1 year. Data were analyzed for outcomes, and the
      literature was reviewed. RESULTS: Four of 6 patients had persistent external
      pancreatic fistulas following pancreatic necrosectomy, 1 had surgery for
      pancreatic pseudocyst, and 1 after pancreaticoduodenectomy for pancreatic head
      mass. An average duration of conservative management was 14 weeks, and Roux-en-Y
      fistulojejunostomy was performed at a median distance of 6 cm from pancreas via a
      midline laparotomy. All patients recovered without major complications. Only 1
      patient developed diabetes at a 1-year follow-up. CONCLUSION: Fistulojejunostomy
      is a safe and effective treatment for persistent pancreatic fistula having the
      benefit of avoiding a difficult major pancreatic resectional surgery in an
      already debilitated patient with frozen tissue planes, along with low
      postoperative morbidity and mortality. The short- and mid-term outcomes in the
      literature for this procedure are good, as it has also been seen in our study on
      diverse indications.

PMID- 30216172
TI  - Development of metabolic syndrome after bilateral total thyroidectomy despite the
      L-t4 replacement therapy: A prospective study.
AB  - OBJECTIVES: The literature about the frequency of metabolic syndrome in patients
      with multinodular goitre and a new onset of metabolic syndrome after total
      thyroidectomy is limited. The aim of this study was to investigate the effects of
      total thyroidectomy and thyroid hormones on a new onset of metabolic syndrome in
      patients who underwent total thyroidectomy and have received thyroid hormone
      replacement. MATERIAL AND METHODS: Fifty-nine patients who underwent total
      thyroidectomy for multinodular goitre were included in this prospective study.
      Patients' height, weight, and waist circumference were measured, and the body
      mass index was calculated. Peripheral blood samples were obtained preoperatively
      and at the 12th and 24th month after total thyroidectomy to examine the lipid
      profile, glucose homeostasis, and thyroid function tests. RESULTS: The lipid
      profile and blood pressure parameters deteriorated, and the mean body mass index
      and waist circumference with the metabolic syndrome rates significantly increased
      at the 12th and 24th months follow-up. Preoperative body mass index (Exp[B] 1.60;
      p=0.003) was independently associated with metabolic syndrome at the 2nd year
      after total thyroidectomyin a multivariate regression analysis. CONCLUSION: The
      frequency and severity of MetS is high in adult patients with non-toxic
      multinodular goitre after total thyroidectomy. The frequency of metabolic
      syndrome increased in patients with a high body mass index after total
      thyroidectomy.

PMID- 30216174
TI  - Prevention of inadvertent injury to aberrant hepatic artery arising from superior
      mesenteric artery during laparoscopic pancreaticoduodenectomy.

PMID- 30216173
TI  - Protective effects of St. John's wort in the hepatic ischemia/reperfusion injury
      in rats.
AB  - OBJECTIVES: The purpose of this study was to investigate possible protective
      effects of St. John's wort in the hepatic ischemia/reperfusion injury. MATERIAL
      AND METHODS: The hepatic artery, portal vein, and bile duct were all clamped for
      45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW
      was administrated orally, once a day for 3 days before ischemia/reperfusion. The
      aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and
      interleukin levels were measured in the serum samples. Luminol chemiluminescence,
      lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium
      ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3
      and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot
      analysis. RESULTS: The St. John's wort administration recovered the aspartate
      aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1beta
      levels serum parameters meaningfully, while ischemia/reperfusion caused an
      increase in luminol chemiluminescence, lucigenin luminol chemiluminescence,
      myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B
      cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+
      ATPase activity. CONCLUSION: The obtained results indicate protective effects of
      St. John's wort on the ischemia/reperfusion injury through various mechanisms,
      and we are able to suggest that St. John's wort can clinically create a new
      therapeutic principle.

PMID- 30216175
TI  - Rare cause of duodenal obstruction: Bouveret syndrome.
AB  - Gallstone ileus is a relatively rare pathology, most commonly obstructing the
      terminal ileum. Bouveret syndrome is a syndrome found particularly in elderly
      patients, which develops as the result of a cholecystoenteric fistula. It leads
      to the gastric outlet obstruction and has an incidence of less than 1%. In this
      report, we presented a 95-year-old patient diagnosed with Bouveret syndrome.

PMID- 30216176
TI  - Cosmetic outcomes of infraumbilical, supraumbilical, and transumbilical entry
      routes in laparoscopic surgery.
AB  - OBJECTIVE: The aim of the present study was to determine which of the umbilical
      entry routes for intraperitoneal access has a better cosmetic result. MATERIAL
      AND METHODS: This was a prospective study (Canadian Task Force classification II
      1). In total, 105 patients who underwent laparoscopic surgery were included. A
      vertical or transverse umbilical incision is appropriately made for the trocar to
      be inserted, and an infraumbilical, supraumbilical, or transumbilical route was
      preferred for initial intraperitoneal access. Demographic data of patients, body
      mass indices, entry point of the trocars (infraumbilical-transumbilical
      supraumbilical), type of incision (vertical-transverse), duration of the
      operation, and scar properties at postoperative week 12 were prospectively
      collected and analyzed. The Vancouver scar scale was used to evaluate the
      cosmetic results. RESULTS: Cosmetic results did not differ statistically between
      the transumbilical-infraumbilical-supraumbilical groups. The variables, such as
      vascularity, height, and total score, of the Vancouver scar scale were
      significantly higher in patients who had transverse incisions. There was no
      statistically significant effect of using a Veress needle with the cosmetic
      results. There was no statistically significant correlation between age, gravida,
      body mass indices, skin thickness, time of entry, duration of the operation, and
      cosmetic results in terms of vascularity, height, and total score. CONCLUSION:
      During laparoscopic surgery, each patient should be assessed individually for the
      satisfaction of the patient and, thereby, of the surgeon in terms of cosmetic
      outcomes. Vertical incision offers superior cosmetic effects than transverse
      incision. Further research is required to define long-term scar-related outcomes
      of the laparoscopic intraperitoneal access techniques.

PMID- 30216177
TI  - Evaluation of the effects of adipose-derived mesenchymal stem cells on
      intraperitoneal adhesions.
AB  - OBJECTIVES: The goal was to examine the efficiency of local implementation of
      adipose-derived mesenchymal stem cells, which have an anti-inflammatory effect,
      in preventing the intra-abdominal adhesions in rats. MATERIAL AND METHODS: Twenty
      one Wistar albino rats were randomly divided into 3 groups, 7 rats in each: Group
      1 was defined as the control group, Group 2 as the sham group, and Group 3 as the
      adipose-derived mesenchymal stem cell group. A 6 cm mid-abdomen incision in the
      all the rats was performed. The cecum serosa and sub-serosa were injured by
      rubbing with a gauze. No agent was applied intraperitoneally for the rats in
      Group 1; 1.5 mL saline and 2x106/kg allojenic adipose-derived mesenchymal stem
      cells in the 1.5 mL saline were injected into peritoneum of rats in Groups 2 and
      3, respectively. Laparotomy was performed on the 14th day. Adhesion scores,
      histopathological examination, E-cadherin expression, and the tissue
      hydroxyproline level were evaluated. RESULTS: The general adhesion score and
      collagen deposition in Group 3 were found to be significantly higher than in
      Groups 1 and 2 (p=0.003 and p=0.009, respectively). In the inflammatory cell
      comparison, a significant decrease was found in Group 3 in proportion to Groups 1
      and 2 (p=0.001, p=0.005, respectively). The E-cadherin levels were found to be
      higher in Group 3 (p=0.003). CONCLUSION: Severe adhesion was observed in the
      adipose-derived mesenchymal stem cells group. Collagen intensity and E-Cadherin
      expression also increased in the adipose-derived mesenchymal stem cells group.
      The anti-inflammatory effect was also seen in the adipose-derived mesenchymal
      stem cells group.

PMID- 30216178
TI  - Evaluation of the readability of informed consent forms used in urology: Is there
      a difference between open, endoscopic, and laparoscopic surgery?
AB  - OBJECTIVES: The aim of this study is to evaluate the readability levels of
      informed consent forms used in Turkey before urological surgery and to compare
      the readability levels of open, endoscopic, and laparoscopic surgical informed
      consent forms. MATERIAL AND METHODS: A total of 529 informed consent forms used
      for urological open, endoscopic, and laparoscopic surgical procedures were
      collected from different hospitals in Turkey. Evaluating informed consent forms
      that have exactly the same text only once, a total of 69 consent forms were
      evaluated. The Gunning Fog Index and Flesch-Kincaid test measuring the general
      readability level were used to calculate the readability level of informed
      consent forms in addition to the Atesman and Bezirci-Yilmaz formulas defined to
      determine the readability level of Turkish texts. Informed consent forms were
      evaluated and divided into three groups as open, endoscopic, and laparoscopic
      surgery forms, depending on their content. RESULTS: Among 69 informed consent
      forms evaluated, 35 were open, 19 were endoscopic, and 15 were laparoscopic
      surgery consent forms. The readability level of all informed consent forms was
      detected as average according to the Atesman formula, very difficult according to
      the Flesch-Kincaid test, difficult according to the Gunning Fog Index, and at the
      high school education level according to the Bezirci-Yilmaz formula. A
      statistical evaluation of the three groups did not show a significant difference
      in the readability level. CONCLUSION: In this study, it was detected that the
      informed consent form readability levels used for urological surgical procedures
      in our country were rather low. We think that the cooperation of the concerned
      institutions is required for the revision of the consent information texts
      available and the improvement of the texts according to the strategies
      recommended.

PMID- 30216180
TI  - Is appendectomy always adequate for treatment?: Clinical manifestations of
      isolated actinomycosis in the appendix.
AB  - Isolated appendiceal actinomycosis is a rare chronic progressive suppurative
      infection. Its causative agent in humans is a Gram-positive saprophytic anaerobic
      bacteria, Actinomyces israelii. We present a case of an acute appendicitis that
      developed in a 54-year-old woman due to isolated appendiceal actinomycosis.
      Diagnosis of appendiceal actinomycosis causing acute appendicitis is generally
      performed postoperatively histopathologically, and appendectomy alone is not
      sufficient for treatment. It is an important factor that should be considered by
      clinicians that definitive treatment of the infection is possible by appropriate
      antibiotic use.

PMID- 30216179
TI  - TLR4 Asp299Gly and Thr399Ile and TLR2 intron 2 microsatellite gene polymorphism
      in patients with acute biliary pancreatitis: Does it cause the disease?
AB  - OBJECTIVES: There has been coverage of Toll-like receptor 4 and Toll-like
      receptor 2 gene polymorphisms in inflammatory episodes in a number of studies. In
      view of the inflammatory nature of acute pancreatitis, we aimed to determine the
      predictive value of mutations in Asp299Gly and Thr399Ile of the Toll-like
      receptor 4 gene, and the intron 2 microsatellite polymorphism of the Toll-like
      receptor 2 gene on the occurrence of acute biliary pancreatitis. MATERIAL AND
      METHODS: The study included 86 patients for the Toll-like receptor 4 Thr399Ile
      polymorphism, 100 patients for the Toll-like receptor 4 Asp299Gly polymorphism
      with acute biliary pancreatitis, and 101 healthy volunteers. At the same time, 93
      patients and 92 healthy volunteers were included in the study to research the
      Toll-like receptor 2 intron 2 microsatellite polymorphism. Genotypes were
      determined using the restriction fragment length polymorphism analysis of PCR
      products and by an allele-specific PCR. RESULTS: The Toll-like receptor 4
      Thr399Ile homozygotes mutant variants (p=0.005) and Toll-like receptor 2 MM
      genotype (p<0.001) were detected with a significantly higher frequency in
      patients with acute biliary pancreatitis than in the healthy blood donors.
      CONCLUSION: The Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and
      the Toll-like receptor 2 intron 2 microsatellite polymorphism are statistically
      associated with ABP.

PMID- 30216181
TI  - Tunica Vaginalis Thickening, Hemorrhagic Infiltration and Inflammatory Changes in
      8 Children with Primary Hydrocele; Reactive Mesothelial Hyperplasia? A
      Prospective Clinical Study.
AB  - The aim of this study is to describe an entity of primary hydrocele accompanied
      with fibrosis, thickening and hemorrhagic infiltration of parietal layer of
      tunica vaginalis (PLTV). During a 4-year period (2011-2014), 94 boys (2.5-14
      years old) underwent primary hydrocele repair. Hydrocele was right sided in 55
      (58.5 %), left sided in 26 (28.7%) and bilateral in 12 patients (13.8%). Eighty
      three out of 94 patients (88.30%) had communicating hydrocele and the rest eleven
      patients (11.7%) had non-communicating. Our case group consists of 8 patients
      (8.51%) based on operative findings consistent with PLTV induration, thickening
      and hemorrhagic infiltration. Preoperative ultrasonography did not reveal any
      pathology of the intrascrotal structures besides hydrocele. There weren't
      hyperechoic reflections or septa within the fluid. Evaluation of thickness of the
      PLTV was not feasible. Presence of lymph or exudate was excluded after fluid
      biochemical analysis. Tunica vaginalis histological examination confirmed
      thickening, hemorrhagic infiltration and inflammation, while there was absence of
      mesothelial cells. Immunochemistry for desmin was positive, excluding malignant
      mesothelioma. One patient underwent high ligation of the patent processus
      vaginalis and PLTV sheath fenestration, but one year later, he faced a
      recurrence. An elective second surgery was conducted via scrotal incision and
      Jaboulay operation was performed. The latter methodology was our treatment choice
      in other 7 out of 8 patients. During a 2-year postoperative follow-up, no other
      patient had any recurrence. We conclude that in primary hydrocele with
      macroscopic features indicative of tunica vaginalis inflammation, reversion of
      the tunica should be a part of operative strategy instead of sheath fenestration,
      in order to minimize the recurrence.

PMID- 30216182
TI  - Electrodermal Activity Monitoring During Painful Stimulation in Sedated Adult
      Intensive Care Unit Patients: a Pilot Study.
AB  - : Introduction-Aim: Newer methods, such as infrared digital pupillometry and
      electrodermal activity (EDA) measurement have been suggested as good alternatives
      for analgesia monitoring in critically ill patients. This study analyzed EDA
      changes due to pain stimulus in sedated adult critical care patients Methods:
      Skin conductance variability, selected hemodynamic and respiratory parameters,
      Bispectral index (BIS) and ambient noise level, were monitored during 4 hour
      routine daytime in an adult ICU. 4h-Measurements were divided into 2 groups,
      based upon the sedation level of the patients: Group A - Ramsay Sedation Score 2
      4 and Group B - Ramsay Sedation Score of 5-6. Selected recordings before and
      after pain stimulus were performed. The stimulus chosen was the pressure applied
      to nail bed for 10 sec, which was performed routinely during neurological
      examination. Patients' demographics, laboratory exams and severity scores were
      recorded. Pain status evaluation before every event was also performed by 2
      independent observers via Critical Care Pain Observation Tool (CPOT) and Adult
      Non Verbal Pain Score (ANVPS) Results: In both groups the rate of EDA changes was
      greater than other monitoring parameters: more in Group A than in Group B. Yet,
      the difference between groups was not statistically significant. CONCLUSION: EDA
      measurements are greater to pain stimuli, than cardiovascular, respiratory or
      even BIS monitoring. These encouraging results suggest that, further studies are
      needed to better define EDA role in ICU.

PMID- 30216183
TI  - Severe Hypocalcemia and Extreme Elevation of Serum Creatinkinase in a 16-Year Old
      Boy with Pseudohypoparathyroidism Type Ib.
AB  - Calcium is essential for proper muscular function and metabolism. Myopathy with
      high creatinkinase activity can be a rare manifestation of hypocalcemia of
      various origin, such as vitamin D deficiency, hypoparathyroidism,
      pseudohypoparathyroidism (PHP). 16-year old previously healthy boy was admitted
      to intensive care unit with convulsions lasting for three minutes and a transient
      loss of consciousness. Laboratory results revealed severe hypocalcemia (total S
      Ca < 1.0 mmol/L; normal 2.2-2.6 mmol/L), hyperphosphatemia (S-P 2.8 mmol/L;
      normal 0.6-1.6 mmol/L). Serum creatinkinase (S-CK) activity was 32 MUkat/L
      (normal 0.57-2.45 MUkat/L). Other basic biochemical parameters including
      creatinine, troponin, alkaline phosphatase were within normal values. Calcemia
      was gradually corrected within two weeks by intravenously and orally administered
      calcium and by cholecalciferol. S-CK reached a maximum of 222 MUkat/L on day 4
      and dropped to 7.2 MUkat/L on day 14. Boy had no myalgias, neither clinical signs
      of myopathy. Echocardiography was normal with normal myocardial contractility,
      without any signs of calcification. The serum level of parathyroid hormone (S
      PTH) was high (12 pmol/L; normal 0.7-5.5 pmol/L), fully compatible with the
      diagnosis of PHP. Molecular analysis revealed pseudohypoparathyroidism type Ib
      (PHPIb).In conclusion, manifest tetany and even mild myopathy with very high S-CK
      can occur in hypocalcemic patients and usually resolves after normalization of
      hypocalcemia.

PMID- 30216184
TI  - A Long-Term Control of Intramedullary Thoracic Spinal Cord Metastasis from Small
      Cell Lung Cancer.
AB  - Radiotherapy with systemic corticosteroid therapy has been used to treat
      intramedullary spinal cord metastasis (ISCM), but recovery of function and long
      term survival of these patients has been rarely observed. We report herein a
      small cell lung cancer (SCLC) patient with recurrent thoracic ISCM, who was
      successfully treated with radiotherapy and systemic corticosteroid therapy. A 70
      year-old man, who was diagnosed as having SCLC seven months previously, developed
      thoracic ISCM. Soon after the detection of the lesion, the patient received
      radiotherapy with systemic corticosteroid therapy. Sensory disturbance in both
      extremities and neurogenic bladder and bowel dysfunction was recovered. The
      patient could walk after irradiation again. The patient received additional
      chemotherapy and survived 20 months after the diagnosis of ISCM recurrence.
      Prompt diagnosis and appropriate treatment for ISCM and effective chemotherapy
      for recurrent SCLC might be the favorable factors for such patients. Further
      studies will be required to define a favorable subset of patients most likely to
      benefit from a conventional approach.

PMID- 30216185
TI  - From Ataxia to Diagnosis of Askin Tumor - a Case Report.
AB  - Peripheral primitive neuroectodermal tumors (pPNET) are a group of extremely
      rare, aggressive, malignant tumors that are most often found in the thorax (Askin
      tumor), abdomen, pelvis, extremities and less frequently in the head and neck.
      The most important prognostic factor is the stage of the tumor. Significant
      progress both in surgery and in neoadjuvant and adjuvant chemotherapy and
      radiotherapy, as well as the improvement in diagnosis by cytogenetic and
      immunohistochemical analysis, should improve the survival rate. We report a case
      of a 14-year-old girl, with ataxic gait, cardiopulmonary compensated, without
      respiratory symptoms, who was referred to our hospital for further examination
      and treatment of newly discovered tumor of the left hemithorax. After a detailed
      radiological and laboratory investigation, next step was an extensive thoraco
      neurosurgical surgery. After histopathological, cytological and molecular
      analysis, a diagnosis of Askin tumor was made.

PMID- 30216186
TI  - Abnormal Communication between Lateral Thoracic Artery and Anterior Circumflex
      Humeral Artery - a Case Report.
AB  - Variations in the branching pattern of axillary artery are observed by many
      anatomists all over the world. A unique bilateral variation in the axillary
      artery was observed during the routine dissection of the upper limbs on an
      approximately 65 year old male cadaver. An abnormal communicative channel was
      observed between lateral thoracic artery and anterior circumflex humeral artery.
      It passed between the two roots of median nerve. Arterial anomalies in the upper
      limb are due to defective remodelling of vascular plexus of the upper limb bud
      during embryogenesis. Knowledge of variations in axillary artery is
      quintessential for surgeons, radiologists and anaesthesiologists to avoid
      treacherous complications during procedures.

PMID- 30216187
TI  - Topping Phenomenon with Recurrent Spinal Stenosis and Epidural Fibrosis Prevented
      with Oxidized Cellulose - a Case Report.
AB  - Lumbar spinal stenosis is a condition where the neural structures are compressed
      in the narrowed spinal canal and often situated only within a single specific
      segment of the spine, most frequently in the lumbar spine. A case report
      demonstrates a surgical solution of lumbar spinal stenosis with using oxidized
      cellulose as a prevention of post-operative adhesions and failed back syndrome. A
      female patient (68) with a significant pain of the lumbar spine lasting for a
      number of months due to advanced spondylosis, failing to respond to conservative
      treatment underwent instrumented, posterolateral fusion of affected segments. The
      patient re-arrived with pain due to spinal stenosis in another segments after 4
      and then after 3 years. We repeatedly performed spinal fusion of the affected
      segments and applied an antiadhesive gel to the dural sac and the decompressed
      nerve roots to prevent the development of post-operative adhesions and the
      "failed back syndrome". Last surgical solution included mobilisation of the
      simultaneously constricted dural sac through laminectomy. This time we covered
      the sac using a haemostat made of oxidized cellulose (Traumacel FAM). After this
      treatment, the patient was again without significant difficulties.

PMID- 30216188
TI  - Cerebral Infarction in Young Marijuana Smokers - Case Reports.
AB  - INTRODUCTION: Causality of marijuana abuse with development of ischemic stroke
      has been indicated by numerous case reports and epidemiological studies. As a
      possible pathophysiological mechanism, the most common consideration is cardiac
      embolization during paroxysmal atrial fibrillation, systemic hypotension or
      multifocal intracerebral vasoconstriction. CASE REPORTS: We present three case
      reports of marijuana consumers who were admitted to our comprehensive stroke
      center due to ischemic stroke within 18-month period of our investigation. In one
      case, the cause of stroke was not related to the use of marijuana, it was a
      manifestation of antiphospholipid syndrome. In two cases the association with the
      abuse of this drug is probable but not certain. In both these cases, an isolated
      occlusion in vertebrobasilar arterial system was detected, without finding of a
      cerebral vessels stenosis. Although we did not register the atrial fibrillation,
      we consider cardiac embolization as probable etiological mechanism of stroke in
      both cases. In one case, paradoxical embolization due to the persistent foramen
      ovale represents another potential etiological mechanism. CONCLUSIONS:
      Cannabinoid use may cause ischemic stroke, especially in the younger age
      category. Therefore, in these patients we recommend focusing on the history of
      cannabinoid abuse and carry out toxicological urine tests.

PMID- 30216189
TI  - Cytosolic DNA Sensing in Organismal Tumor Control.
AB  - Besides constituting a first layer of defense against microbial challenges, the
      detection of cytosolic DNA is fundamental for mammalian organisms to control
      malignant transformation and tumor progression. The accumulation of DNA in the
      cytoplasm can initiate the proliferative inactivation (via cellular senescence)
      or elimination (via regulated cell death) of neoplastic cell precursors.
      Moreover, cytosolic DNA sensing is intimately connected to the secretion of
      cytokines that support innate and adaptive antitumor immunity. Here, we discuss
      the molecular mechanisms whereby cytosolic DNA enables cell-intrinsic and 
      extrinsic oncosuppression, and their relevance for the development of novel
      therapeutic approaches that reinstate anticancer immunosurveillance.

PMID- 30216190
TI  - Integrating Population Health Content into FNP Program Curriculum.
AB  - In the current healthcare environment, the healthcare industry has become
      increasingly focused on population health concerns. While advanced practice
      registered nurses (APRNs) are well prepared to contribute to population health by
      delivering holistic healthcare to individuals, families, groups, communities, and
      populations, they are not engaged in initiatives to improve population health
      commensurate with their numbers, education, training, experience, and role as
      primary care providers and essential healthcare team leaders and members. This
      article discusses the rationale for integrating population health into APRN
      curricula, one program's approach to doing so, and preliminary lessons learned
      from this effort. The three main lessons learned include population health
      content should be integrated across the curriculum for all APRN cohorts,
      supplementary population health content should be considered, and opportunities
      for integrating didactic population health content should be included across the
      FNP curriculum.

PMID- 30216191
TI  - Randomised trial of HPV self-sampling among non-attenders in the Slovenian
      cervical screening programme ZORA: comparing three different screening
      approaches.
AB  - Background To overcome obstacles within the Slovenian organised cervical cancer
      screening programme, a randomised pilot study of human papillomavirus (HPV) self
      sampling among non-attenders was performed, aiming to assess three different
      screening approaches. Participants and methods Non-attenders aged 30-64 years
      from two Slovenian regions were randomised to two HPV self-sampling groups-the
      opt-in (I1, n = 14.400) and the opt-out (I2, n = 9.556), with a control group (P,
      n = 2.600). Self-collected samples were analysed using the Hybrid Capture 2
      assay. HPV-positive women were invited to a colposcopy. The overall and type
      specific intention-to-screen response rates and histological outcomes with a
      positive predictive value (PPV) according to the women's age, the screening
      approach, the level of protection resulting from previous screening history, and
      the region of residence were assessed. Results Of the 26.556 women enrolled,
      8.972 (33.8%) responded with self-sample for HPV testing and/or traditional
      cytology within one year of enrolment. Response rates were 37.7%, 34.0% and 18.4%
      (p < 0.050) for opt-out, opt-in and control groups. Cervical intraepithelial
      neoplasia (CIN)2+ was diagnosed in 3.9/1.000, 3.4/1.000, and 3.1/1.000 women (p >
      0.050), respectively. PPV of the HPV self-sampling was 12.0% and 9.6% for CIN2+
      and CIN3+. The highest PPV was obtained in non-attenders in screening programme
      for more than 10-years and concordant results of HPV testing with 40.8% for CIN2+
      and 38.8% for CIN3+. Conclusions The results of our study show that a high
      response to HPV self-sampling can be achieved also in an opt-in approach, if
      women are encouraged to choose between self-sampling at home and screening with
      gynaecologist. In addition, clinically important risk difference for a high-grade
      cervical lesion exists in the case of a positive result of HPV testing on self
      collected samples, depending on the length of the interval since last screening.
      Stratified management of these women should be strongly considered. Women who
      were not screened with cytology for at least 10 years should be referred to
      immediate colposcopy for histology verification instead to delayed re-testing.

PMID- 30216192
TI  - Fabrication of high-quality copper nanowires flexible transparent conductive
      electrodes with enhanced mechanical and chemical stability.
AB  - Copper nanowires (Cu NWs) become a potential functional material in future
      optoelectronic devices owing to their high optical transmittance, super
      electrical conductivity, and good flexibility as well as low cost. However, the
      drawbacks of Cu NWs with large contact resistance and poor stability make them
      far from the practical implementations. Herein we report a robust method to
      fabricate high-quality Cu NWs transparent conductive electrodes (TCEs) with
      enhanced mechanical and chemical stability at room temperature. Firstly, we used
      a sodium borohydride (NaBH4) treatment to remove the organics and oxides on
      surface of Cu NWs and thus greatly improved the conductivity of Cu NWs TCEs.
      Subsequently, followed by decorating a dense hydrophobic dodecanethiol (DT)
      protective layer, the formed Cu NWs TCEs showed superior mechanical and chemical
      stability compared to the raw ones. The optimized Cu NWs TCEs exhibit a sheet
      resistance of ~38 Omega/sq at an optical transmittance of 83% (550 nm). Unlike
      the bare Cu NWs, the DT-decorated Cu NWs showed good stability under humid
      conditions at (85% RH) at 85  degrees C for 12 h. Moreover, the DT-decorated Cu
      NW TCEs were tested as transparent heaters, showing the fast response time and
      high saturation temperature under a low DC voltage. Our studies demonstrate that
      the proper post treatments for Cu NWs TCEs would make them more competitive in
      application of next-generation electronic and optoelectronic devices.

PMID- 30216193
TI  - Spray deposition and characterization of carbon nanoflower and gold-doped carbon
      nanoflower thin films.
AB  - Herein, we present an aerosol filtration method for the fabrication of carbon
      nanoflower (CNF) thin films. The method was based on generation, evaporation and
      filtration of solvent encapsulated CNF droplets. The particles were collected on
      polytetrafluoroethylene membranes and roll-transferred at room temperature onto
      flexible polyethylene terephthalate substrates. Suspensions for spraying were
      made in low vapor pressure mixtures of EtOH/Hex (50/50 v/v%). Doping of starter
      suspensions was made by the addition of organometallic 1-dodecanethiol-coated
      gold nanoparticles (AuNPs). The produced films displayed substrate surface
      coverage of up to 83.3% +/- 13.9% and a film thickness of up to 2.4 MUm. The
      deposition of doped suspensions resulted in uniform distribution of AuNPs in the
      volume of the CNF film, which enables film application for flexible
      photovoltaics.

PMID- 30216194
TI  - Patterns of Care and Outcomes of Elderly Esophageal Cancer Patients Not Meeting
      Age-based Criteria of the CROSS Trial.
AB  - OBJECTIVES: The CROSS trial established neoadjuvant chemoradiation followed by
      surgery (nCRT-S) as superior to surgery alone (S) for locally advanced esophageal
      cancer (EC). However, because patients above 75 years of age were excluded, this
      comparison cannot be extrapolated to older patients. This study of a large,
      contemporary national database evaluated practice patterns in elderly patients
      ineligible for CROSS, and analyzed overall survival (OS) between nCRT+S, S, and
      definitive CRT (dCRT). MATERIALS AND METHODS: The National Cancer Data Base was
      queried for EC patients with cT1N1M0/T2-3N0-1M0 EC (per the CROSS trial) but 76
      years and above of age. Multivariable logistic regression ascertained factors
      associated with nCRT+S (vs. S). Kaplan-Meier analysis evaluated OS; Cox
      multivariate analysis determined variables associated with OS. Propensity
      matching aimed to address group imbalances and indication biases. RESULTS: Of
      4099 total patients, 594 (14%) underwent nCRT+S, 494 (12%) underwent S, and 3011
      (73%) underwent dCRT. Since 2010, trimodality management has risen, corresponding
      to declines in S and dCRT. Median OS in the respective groups were 26.7, 20.3,
      and 17.8 months (P<0.05). Following propensity matching, there was a trend
      towards higher OS with nCRT-S over S (P=0.077); dCRT showed poorer OS than nCRT-S
      (P<0.001) but was equivalent to S (P=0.669). Before and following matching, nCRT
      S experienced equivalent 30- and 90-day mortality as S (P>0.05), with lower 30
      day readmission and postoperative hospital stay (P<0.05). CONCLUSIONS: Although
      most older patients not meeting CROSS criteria undergo dCRT, utilization of
      trimodality therapy is rising. Despite the trend towards higher OS with
      trimodality therapy without poorer postoperative outcomes, careful patient
      selection continues to be essential in this population.

PMID- 30216196
TI  - Intrafamilial variability of clinical features in distal arthrogryposis type 2B.

PMID- 30216195
TI  - Nurses' Perceptions of Engaging With Patients to Reduce Restrictive Practices in
      an Inpatient Psychiatric Unit.
AB  - Despite the evidence of harmful effects of restrictive practices on patients and
      nurses, restrictive practices are still commonly used in the inpatient
      psychiatric settings. There has been a paradigm shift of a collaborative approach
      and implementation of patient engagement to reduce the use of restrictive
      practices. The purpose of this study was to explore nurses' perceptions of
      engaging with patients to reduce the use of restrictive practices in an inpatient
      psychiatric unit. This qualitative-descriptive study was conducted on an
      inpatient psychiatric unit of a large university hospital in Canada.
      Semistructured individual interviews were conducted with 6 nurses in 2016. Data
      generated by the interviews were coded and analyzed by thematic analysis. Four
      major themes emerged from the data analysis: unit engagement practices, managing
      the escalation by engaging with patient, engaging during the use of restrictive
      practices, and factors influencing engaging with patient to reduce restrictive
      practices. It is concluded that nurses perceive engaging with patients as
      possible and effective to reduce the use of restrictive practices despite
      identified barriers.

PMID- 30216197
TI  - Continuous Erector Spinae Plane and Intrathecal Opioid Analgesia: Novel Regimen
      Avoiding Thoracic Epidural Analgesia and Systemic Morphine in Open Radical
      Cystectomy: A Case Series.
AB  - There has been a significant shift away from epidural analgesia after radical
      cystectomy within an enhanced recovery program. Alternative techniques reported
      including continuous erector spinae plane analgesia require supplemental systemic
      morphine. A new analgesic regimen is described that avoids both thoracic epidural
      analgesia and systemic morphine. Three adult patients undergoing open radical
      cystectomy, who refused thoracic epidural analgesia, were offered continuous
      erector spinae plane and intrathecal opioid analgesia. Median length of hospital
      stay was reduced by a third. The novel analgesic regimen may have the potential
      to enhance recovery after open radical cystectomy.

PMID- 30216198
TI  - Noninvasive Administration of Inhaled Epoprostenol and Inhaled Milrinone in
      Extubated, Spontaneously Breathing Patients With Right Ventricular Failure and
      Portal Hypertension: A Report of 2 Cases.
AB  - We describe the cases of 2 patients free from mechanical ventilation after a
      cardiac surgery with systemic venous congestion from right ventricular (RV)
      failure. Management of these patients included RV preload reduction with
      diuretics and RV afterload reduction with inhaled pulmonary vasodilators.
      Noninvasive combination of inhaled epoprostenol and inhaled milrinone through the
      AirLife filtered nebulizer system (CareFusion) was used. Reduction of splanchnic
      venous congestion was assessed by Doppler portal flow pulsatility.

PMID- 30216200
TI  - Expression and clinical significance of S100 family genes in patients with
      melanoma.
AB  - Genes in the S100 family are abnormally expressed in a variety of tumor cells and
      are associated with clinical pathology, but their prognostic value in melanoma
      patients has not yet been fully elucidated. In this study, we extracted and
      profiled S100 family mRNA expression data and corresponding clinical data from
      the Gene Expression Omnibus database to analyze how expression of these genes
      correlates with clinical pathology. Compared with normal skin, S100A1, S100A13,
      and S100B were expressed at significantly higher levels in melanoma samples.
      S100A2, S100A7, S100A8, S100A9, S100A10, S100A11, and S100P were all highly
      expressed in primary melanoma samples but were expressed at low levels in
      metastatic melanoma, and all of these genes were strongly correlated with each
      other (P<0.001). We found the expression of these S100 family genes to be
      significantly correlated with both lymphatic and distant melanoma metastasis, as
      well as with American Joint Committee on Cancer grade but not with Clark's grade,
      age, or sex. This suggests that expression of these genes may be related to the
      degree of tumor invasion. Although further validation through basic and clinical
      trials is needed, our results suggest that the S100 family genes have the
      potential to play an important role in the diagnosis of melanoma. S100 expression
      may be related to tumor invasion and may facilitate the early diagnosis of
      melanoma, allowing for a more accurate prognosis. Targeted S100 therapies are
      also potentially viable strategies in the context of melanoma.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- 30216199
TI  - Postsurgical treatment landscape and economic burden of locoregional and distant
      recurrence in patients with operable nonmetastatic melanoma.
AB  - Surgery is the mainstay treatment for operable nonmetastatic melanoma, but
      recurrences are common and limit patients' survival. This study aimed to describe
      real-world patterns of treatment and recurrence in patients with melanoma and to
      quantify healthcare resource utilization (HRU) and costs associated with episodes
      of locoregional/distant recurrences. Adults with nonmetastatic melanoma who
      underwent melanoma lymph node surgery were identified from the Truven Health
      MarketScan database (1 January 2008 to 31 July 2017). Locoregional and distant
      recurrence(s) were identified on the basis of postsurgery recurrence indicators
      (i.e. initiation of new melanoma pharmacotherapy, new radiotherapy, or new
      surgery; secondary malignancy diagnoses). Of 6400 eligible patients, 219 (3.4%)
      initiated adjuvant therapy within 3 months of surgery, mostly with interferon
      alpha-2b (n=206/219, 94.1%). A total of 1191/6400 (18.6%) patients developed
      recurrence(s) over a median follow-up of 23.1 months (102/6400, 1.6% distant
      recurrences). Among the 219 patients initiated on adjuvant therapy, 73 (33.3%)
      experienced recurrences (distant recurrences: 13/219, 5.9%). The mean total all
      cause healthcare cost was $2645 per patient per month (PPPM) during locoregional
      recurrence episodes and $12 940 PPPM during distant recurrence episodes. In the
      year after recurrence, HRU was particularly higher in patients with distant
      recurrence versus recurrence-free matched controls: by 9.2 inpatient admissions,
      54.4 inpatient days, 8.8 emergency department admissions, and 185.9 outpatient
      visits (per 100 person-months), whereas all-cause healthcare costs were higher by
      $14 953 PPPM. It remains to be determined whether the new generation of adjuvant
      therapies, such as immune checkpoint inhibitors and targeted agents, will
      increase the use of adjuvant therapies, and reduce the risk of recurrences and
      associated HRU/cost.

PMID- 30216201
TI  - Health Care Access and Physical and Behavioral Health Among Undocumented Latinos
      in California.
AB  - BACKGROUND: This paper provides statewide estimates on health care access and
      utilization patterns and physical and behavioral health by citizenship and
      documentation status among Latinos in California. METHODS: This study used data
      from the 2011-2015 California Health Interview Survey to examine health care
      access and utilization and physical and behavioral health among a representative
      sample of all nonelderly Latino and US-born non-Latino white adults (N=51,386).
      Multivariable regressions estimated the associations between the dependent
      measures and citizenship/documentation status among Latinos (US-born, naturalized
      citizen, green card holder, and undocumented). RESULTS: Adjusted results from
      multivariable analyses observed worse access and utilization patterns among
      immigrant Latinos compared with US-born Latinos, with undocumented immigrants
      using significantly less health care. Undocumented Latinos had lower odds of self
      reporting excellent/very good health status compared with US-born Latinos,
      despite them having lower odds of having several physical and behavioral health
      outcomes (overweight/obesity, physician-diagnosed hypertension, asthma, self
      reported psychological distress, and need for behavioral health services). Among
      those reporting a need for behavioral health services, access was also worse for
      undocumented Latinos when compared with US-born Latinos. CONCLUSIONS: Patterns of
      poor health care access and utilization and better physical and behavioral health
      are observed across the continuum of documentation status, with undocumented
      immigrants having the worst access and utilization patterns and less disease.
      Despite fewer reported diagnoses and better mental health, undocumented Latinos
      reported poorer health status than their US-born counterparts.

PMID- 30216202
TI  - Postpartum Mothers' Experiences With Newborn Weight Checks in the Home.
AB  - Few researchers have examined the perspectives of breastfeeding mothers about
      using a pediatric scale in the home to monitor infant weight. A cross sectional
      design was used to measure helpfulness, impact on newborn feeding, and confidence
      among mothers who used a digital scale to monitor newborn weight. Women (N = 69)
      who had given birth in a community hospital in the Northeast region of the United
      States used a pediatric scale in the home daily for 2 weeks after birth. An
      online survey determined helpfulness of the scale, if use of the scale impacted
      feedings, and confidence in breastfeeding. Using a pediatric scale to monitor
      newborn weight was very helpful (n = 49; 71%); it was most helpful for
      primiparous women (P < .016). Feeding frequency often changed on the basis of
      neonatal weight (n = 27; 39%) but only 9% (n = 6) changed the type of milk fed.
      Confidence in breastfeeding increased in 90% (n = 62) of participants. A
      pediatric scale used in the home to monitor newborn weight is helpful for
      breastfeeding, especially for primiparous women. Use of the scale may increase
      maternal confidence in breastfeeding and help guide decisions about feeding
      frequency.

PMID- 30216203
TI  - Sustained Viral Response in Genotype 4 Chronic Hepatitis C Virus-infected
      Children and Adolescents Treated With Sofosbuvir/Ledipasvir.
AB  - OBJECTIVES: Recently, direct acting antivirals (DAAs), sofosbuvir (SOF) combined
      with ledipasvir (LED), were approved for treatment of hepatitis C virus (HCV)
      infected children 12 years of age and older or weighting at least 35 kg for all
      HCV genotypes. The aim of this study was to assess the safety and efficacy of
      SOF/LED in genotype 4 HCV-infected Egyptian children and adolescents. METHODS:
      This observational study included 40 consecutive HCV-infected children of age 12
      to <18 years old or weighing >35 kg, both treatment-naive and treatment
      experienced. All of the children were hepatitis B virus-negative and had normal
      renal functions and heart rate. Patients received oral, fixed-dose combination
      tablet of SOF/LED (400 mg SOF, 90 mg LED [Harvoni]) once daily for 12 weeks.
      Potential side effects were recorded at weeks 4, 8, and 12 weeks of treatment.
      The study primary outcome was sustained virological response 12 weeks (SVR12)
      after end-of-treatment. RESULTS: The study included 40 children and adolescents,
      24 were boys (60%); their age ranged between 11.5 and 17.5 years (mean 13.9 +/-
      1.5). Baseline viral load ranged between 9630 and 24,600,000 IU/mL. HCV RNA
      became negative in 39 patients (97.5%) at 4 weeks and in all patients (100%) at
      weeks 8, 12, and SVR12. Asthenia was the commonest side effect, reported in 52.5%
      followed by headache in 47.5%. CONCLUSIONS: Treatment with all-oral DAAs
      (SOF/LED) for 12 weeks was well tolerated in Egyptian children and adolescents
      infected with genotype 4 HCV, with 100% SVR12 and negligible side effects.

PMID- 30216205
TI  - Reduced Electrode Arrays for ICU-Continuous EEG Seizure Detection: Minding the
      Methods and Keeping Perspective.

PMID- 30216204
TI  - Validity Evidence for Direct Observation of Procedural Skills in Paediatric
      Gastroscopy.
AB  - OBJECTIVES: Direct observation of procedural skills (DOPS) are competence
      assessment tools in endoscopy. Formative paediatric gastroscopy DOPS were
      implemented into the UK curriculum in 2016 but lack validity evidence; we aimed
      to assess validity evidence using a recognised contemporary validity framework.
      METHODS: We performed a prospective UK-wide analysis of formative paediatric
      gastroscopy DOPS submitted to the e-Portfolio over 1 year. Internal structure
      validity was assessed using interitem correlations between DOPS items, average
      domain, and skillset scores and with the overall competency rating. Overall
      competence scores and mean DOPS scores were compared by trainee seniority and
      procedure count (discriminative validity). Receiver operating characteristic
      curve analysis was performed to explore if DOPS scores could be used to delineate
      procedural competency (consequential validity). RESULTS: A total of 157 DOPS
      assessments were completed by 20 trainers for 17 trainees. Strengths of
      correlations varied between DOPS components, with overall competency correlating
      most with technical-predominant items, domains and skillsets. Both the overall
      assessor's rating and mean DOPS scores increased with trainee seniority (P <
      0.001) and lifetime procedure count (P < 0.001). Overall competency could be
      delineated using mean DOPS scores (area under receiver operating characteristic
      curve 0.95, P < 0.001), with a threshold of 3.9 providing optimal sensitivity
      (94.4%) and specificity (89.7%). CONCLUSIONS: Competencies in paediatric
      gastroscopy, as assessed using DOPS, vary in their correlation with overall
      competence and increase with trainee experience. Formative DOPS thresholds could
      be used to indicate readiness for summative assessment. Our study therefore
      provides evidence of internal structure, discriminative, and consequential
      validity in support of formative paediatric gastroscopy DOPS.

PMID- 30216206
TI  - Reply to: Reduced Electrode Arrays for ICU-Continuous EEG Seizure Detection:
      Minding the Methods and Keeping Perspective.

PMID- 30216207
TI  - EEG Reactivity Evaluation Practices for Adult and Pediatric Hypoxic-Ischemic Coma
      Prognostication in North America.
AB  - PURPOSE: The aim of this study was to assess the variability in EEG reactivity
      evaluation practices during cardiac arrest prognostication. METHODS: A survey of
      institutional representatives from North American academic hospitals
      participating in the Critical Care EEG Monitoring Research Consortium was
      conducted to assess practice patterns involving EEG reactivity evaluation. This
      10-question multiple-choice survey evaluated metrics related to technical,
      interpretation, personnel, and procedural aspects of bedside EEG reactivity
      testing and interpretation specific to cardiac arrest prognostication. One
      response per hospital was obtained. RESULTS: Responses were received from 25
      hospitals, including 7 pediatric hospitals. A standardized EEG reactivity
      protocol was available in 44% of centers. Sixty percent of respondents believed
      that reactivity interpretation was subjective. Reactivity bedside testing always
      (100%) started during hypothermia and was performed daily during monitoring in
      the majority (71%) of hospitals. Stimulation was performed primarily by
      neurodiagnostic technologists (76%). The mean number of activation procedures
      modalities tested was 4.5 (SD 2.1). The most commonly used activation procedures
      were auditory (83.3%), nail bed pressure (63%), and light tactile stimuli (63%).
      Changes in EEG amplitude alone were not considered consistent with EEG reactivity
      in 21% of centers. CONCLUSIONS: There is substantial variability in EEG
      reactivity evaluation practices during cardiac arrest prognostication among North
      American academic hospitals. Efforts are needed to standardize protocols and
      nomenclature according with national guidelines and promote best practices in EEG
      reactivity evaluation.

PMID- 30216208
TI  - Using a corkscrew-tipped telescopic nail in the treatment of osteogenesis
      imperfecta: a biomechanical study and preliminary results of 17 consecutive
      cases.
AB  - High complication rates were reported with the telescopic nail technique systems.
      To overcome such technical difficulties, we designed a corkscrew-tipped
      telescopic nail (CTTN). We biomechanically compared its pullout strength with
      that of two other tip designs. We used CTTN in 17 patients with osteogenesis
      imperfecta and reported their preliminary results. Average patient age was 82.6
      months, and mean follow-up was 32.0+/-6 months. Telescoping and osteotomy site
      healing were assessed using radiological studies. Successful telescoping with
      event-free osteotomy site healing was achieved in 94.1% of patients; limited
      telescoping and delayed union were detected in one case each. Our results show
      that CTTN provides sufficient pullout strength and reduced complication rates
      compared with other designs.

PMID- 30216209
TI  - Dupuytren's disease in a child: a long-term evolution after surgery.
AB  - We report the case of a 13-year-old girl who presented with a fibrous nodular
      lesion on the palm of her hand. After ultrasonographic examination, surgical
      resection of the skin (dermofasciectomy) was performed, and a nodular phase mass
      was recovered, characterized as fusocellular fibroblast proliferation in a dense
      collagenous stroma with a cell population consisting of parallel fascicles of
      densely packed fusiform cells of a fibroblast strain. No signs of encapsulation
      or malignant changes were observed, all of which was consistent with Dupuytren's
      disease. This lesion is exceptional in childhood. Sixteen years later, the
      patient has not relapsed, and retains full active and passive mobility.
      Dupuytren's disease in childhood must be considered in the differential diagnosis
      of any hard palmar lesion. Diagnostic uncertainty and the fact that a hard palmar
      lesion in children may be clinically indistinguishable from a malignant process
      mean that resection of the lesion and histological examination are required.

PMID- 30216210
TI  - Buttress plating for volar Barton fractures in children: Salter-Harris II distal
      radius fractures in sagittal plane.
AB  - We observed an unusual type of volar Barton fracture in the pediatric age and
      performed open reduction and internal fixation of the fragment, using the
      buttress plate in consecutive children. We report the radiological and clinical
      outcomes after follow-up for at least 3 years. From March 2008 to September 2014,
      nine consecutive children were treated by buttress plating. Their mean age at the
      time of injury was 13.1 years. All of the fractures were metaphyseal fractures in
      the coronal plane and typical Salter-Harris II fractures in the sagittal plane.
      After accurate reduction of the fragment, a cortical screw was inserted in the
      proximal area until the maximum compressive force against the fragment was
      obtained. Then, one or two locking screws were added adjacent to the initial
      cortical screw. No screw was fixed in the distal fragment. All evaluations were
      done at least 3 years postoperatively with a mean follow-up of 48.8 months. At
      final follow-up, the radial inclinations, volar tiltings, and ulnar variances
      were 23.2 degrees +/-1.78 degrees  (98.7% of contralateral side), 9.4 degrees +/
      2.12 degrees  (98.4% of contralateral side), and -1.56+/-0.88 mm (93% of
      contralateral side), respectively. All radiological parameters of the distal
      radius were not significantly different from the contralateral values. The
      flexion-extension arc was 140.56 degrees +/-5.27 degrees , and the pronation
      supination arc was 165.00 degrees +/-8.29 degrees . The grip strength was 26.67+/
      5.56 kg. All clinical outcomes except the flexion-extension arc were similar to
      those of the normal side, with statistical significance. A volar Barton type
      injury can occur in the pediatric age involving the physis, and the buttress
      plating that is used in adults is also a useful treatment method. However, there
      is little information on this injury, and it was difficult to compare treatment
      outcomes with other methods. Because of the rarity of the injury, a larger,
      multicenter prospective comparative study is required to further explore
      appropriate treatment options, long-term outcomes, and complications. Level of
      Evidence: Therapeutic, Level IV.

PMID- 30216211
TI  - The effectiveness of phenobarbital in patients with refractory status epilepticus
      undergoing therapeutic plasma exchange.
AB  - This study aimed to elucidate the therapeutic concentration range of
      phenobarbital (PB) for adults, as well as the influence of therapeutic plasma
      exchange (TPE) on plasma concentration of PB. We retrospectively reviewed
      consecutive patients diagnosed with refractory status epileptic (RSE) and treated
      with a bolus injection of PB as well as TPE, admitted to our neurocritical care
      unit from November 2015 to October 2016. Continuous electroencephalographic
      monitoring was performed routinely for these patients. TPE was performed using a
      continuous-flow cell separator. PB concentrations in the plasma and cerebrospinal
      fluid were measured by gas chromatography-mass spectrometer analysis before and
      after TPE. A total of seven patients were included; among these, one patient had
      RSE related to anti-N-methyl-D-aspartate receptor encephalitis, another patient
      had Hashimoto encephalopathy, and five patients had undetermined etiology. For
      patients with clinical and electrographic control (n=6), the plasma concentration
      of PB ranged from 138 to 243.7 MUg/ml. In addition, of six paired plasma samples
      (before and after TPE) obtained from three patients, no significant differences
      between the concentrations of PB were detected (P=0.6), suggesting that TPE may
      not significantly affect the plasma concentration of PB. This study confirmed
      that PB more than 100 ug/ml was effective for adults with RSE. Moreover, TPE may
      not have an influence on the plasma concentration of PB.Video abstract:
      http://links.lww.com/WNR/A489.

PMID- 30216212
TI  - State of the States: Growing Physiatry: Association of Academic Physiatrists
      Position Statement Addressing Academic Physiatry and Physical Medicine and
      Rehabilitation Growth.
AB  - The growth of physiatry in the United States is dependent on academic exposure at
      both the undergraduate and graduate medical education levels. Undergraduate
      medical education provides students with knowledge of physiatry, as well as
      proper understanding of human function, medical rehabilitation treatments, and of
      physiatrists as consultants. Graduate medical education contributes more directly
      to the total number of practicing physiatrists. This article presents disparities
      in medical student exposure to physiatry, physical medicine and rehabilitation
      residency positions, the number of practicing physiatrists, and physical medicine
      and rehabilitation-relevant patient care needs, by state. In the model, these
      disparities are highlighted to provide guidance and expose gaps/opportunities for
      targeted physiatric growth.

PMID- 30216213
TI  - Nasal Airway Clearance for Bronchiolitis.
AB  - Bronchiolitis is a leading cause of emergency department visits and
      hospitalization in the first year of life with estimated costs to the healthcare
      system in the United States of $1.73 billion annually. The highest rates of
      admission occur in the first 3 to 6 months of life. Traditional therapies such as
      bronchodilators and antibiotics have repeatedly been shown to be ineffective.
      Thickened nasal secretions cause decreased oxygenation, difficulty sleeping, poor
      feeding, and respiratory distress symptoms. Bronchiolitis guidelines recommend
      supportive care such as noninvasive nasal airway clearance with saline to clear
      obstructed airways, improve oxygenation, and promote optimal infant eating and
      sleeping. Evidence on the safety and efficacy of use of noninvasive nasal airway
      clearance as supportive care for infants with bronchiolitis in the acute care
      setting is presented.

PMID- 30216214
TI  - Airway Clearance of the Term Newborn.
AB  - PURPOSE: This descriptive, observational study explored the practice of airway
      clearance of the term newborn at birth. The American Academy of Pediatrics, the
      American Heart Association, and the European Resuscitation Council have
      established guidelines for suctioning the well newborn. STUDY DESIGN AND METHODS:
      Airway clearance practices of nurses, obstetricians, and respiratory therapists
      at 10 cesarean births and 10 vaginal births were observed. Data were analyzed
      using descriptive statistics and through content analysis of narratives. RESULTS:
      All newborns observed experienced at least one airway clearance event and
      multiple airway clearance passes. Indications for suctioning were not consistent
      with professional guidelines. Airway clearance procedures and practices were
      inconsistent. Two suction devices used: the blue bulb syringe and orogastric
      catheter. If a newborn was suctioned three times, the orogastric catheter was the
      predominate device used. CLINICAL IMPLICATIONS: There was a lack of adherence to
      established clinical guidelines for newborn airway clearance. Further study is
      needed to identify education of airway clearance guidelines. Specific protocols
      such as safe suctioning methods, correct device use, and observation of
      complications associated with airway management need to be developed to support a
      newborn's healthy transition at birth.

PMID- 30216215
TI  - Airway Clearance of the Term Newborn.
AB  - PURPOSE: The purpose of this study was to explore airway clearance practices for
      the preterm newborn in the neonatal intensive care unit (NICU). STUDY DESIGN AND
      METHODS: This descriptive, retrospective medical record review analyzed airway
      clearance practices in a level III regional NICU from 2016 to 2017 in preterm
      newborns ranging from 32 weeks to 36 weeks and 6 days. There were 87 preterm
      newborns and 384 suctioning events reviewed during the entire length of stay.
      Practices reviewed include device used, frequency, color, consistency, and
      tolerance of airway clearance. Method of nursing documentation for these
      practices was also reviewed. RESULTS: Babies born via cesarean required more
      suctioning (65.5%). Males (60.9%) required more airway clearance events than
      females (39.1%). After suction events, nurses reported no distress (74%), equal
      bilateral breath sounds (30%), desaturation (6%), and collectively color change,
      apnea, or bradycardia (<1%). The most common discharge diagnosis was respiratory
      distress syndrome (90%). Preterm newborns were suctioned with the blue bulb
      syringe (15.6%), oral/nasal-pharyngeal suction device (42.7%), and endotracheal
      suction devices (41.7%). CLINICAL IMPLICATIONS: Electronic medical records
      promote less detailed, narrative documentation and more point and click
      documentation. If electronic medical record systems are not designed to gather
      airway clearance indications, specifics about the procedure and the preterm
      newborn response to the procedure, evidence-based practice cannot be measured.
      More studies are needed to evaluate suction practices applied in the NICU
      setting.

PMID- 30216216
TI  - Response to: "Annals of Surgery Response to Letter to the Editor".

PMID- 30216217
TI  - Response: "Does Surgeon Sex Matter? Practice Patterns and Outcomes of Female and
      Male Surgeons".

PMID- 30216218
TI  - Assessing the Risks of Breast Implants and FDA's Vision for the National Breast
      Implant Registry.

PMID- 30216219
TI  - Circulating Tumor Cells are an Independent Predictor of Shorter Survival in
      Patients Undergoing Resection for Pancreatic and Periampullary Adenocarcinoma.
AB  - OBJECTIVE: We evaluated the prognostic impact of circulating tumor cells (CTCs)
      for patients with presumed resectable pancreatic and periampullary cancers.
      SUMMARY OF BACKGROUND DATA: Initial treatment decisions for this group are
      currently taken without a reliable prognostic marker. The CellSearch system
      allows standardized CTC-testing and has shown excellent specificity and
      prognostic value in other applications. METHODS: Preoperative blood samples from
      242 patients between September 2009 and December 2014 were analyzed. One hundred
      seventy-nine patients underwent tumor resection, of whom 30 with stage-I tumors
      and duodenal cancer were assigned to the low-risk group, and the others to the
      high-risk group. Further 33 had advanced disease, 30 benign histology.
      Observation ended in December 2016. Cancer-specific survival (CSS) and disease
      free survival (DFS) were calculated by log-rank and Cox regression. RESULTS: CTCs
      (CTC-positive; >=1 CTC/7.5 mL) were detected in 6.8% (10/147) of the high-risk
      patients and 6.2% (2/33) with advanced disease. No CTCs (CTC-negative) were
      detected in the low-risk patients or benign disease. In high-risk patients,
      median CSS for CTC-positive versus CTC-negative was 8.1 versus 20.0 months (P <
      0.0001), and DFS 4.0 versus 10.5 months (P < 0.001). Median CSS in advanced
      disease was 7.7 months. Univariate hazard ratio (HR) of CTC-positivity was 3.4 (P
      < 0.001). In multivariable analysis, CTC-status remained independent (HR: 2.4, P
      = 0.009) when corrected for histological type (HR: 2.7, P = 0.030), nodal status
      (HR: 1.7, P = 0.016), and vascular infiltration (HR: 1.7, P = 0.001). CONCLUSION:
      Patients testing CTC-positive preoperatively showed a detrimental outcome despite
      successful tumor resections. Although the low CTC-rate seems a limiting factor,
      results indicate high specificity. Thus, preoperative analysis of CTCs by this
      test may guide treatment decisions and warrants further testing in clinical
      trials.

PMID- 30216221
TI  - Microsatellite Instability (MSI) as an Independent Predictor of Pathologic
      Complete Response (PCR) in Locally Advanced Rectal Cancer: A National Cancer
      Database (NCDB) Analysis.
AB  - OBJECTIVE: The relationship between microsatellite instability (MSI) and response
      to neoadjuvant chemoradiation in rectal cancer is not well understood.
      BACKGROUND: We utilized the National Cancer Database (NCDB) to investigate the
      association between MSI and pathologic complete response (pCR) in this patient
      population. METHODS: We analyzed 5086 patients between 2010 and 2015 with locally
      advanced rectal cancer who were tested for MSI and treated definitively with
      chemoradiation followed by surgery. Primary comparison groups were between 4450
      MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression
      analysis was conducted to identify demographic, therapeutic, and clinical
      characteristics predictive of pCR. Cox proportional-hazard ratios were used for
      survival. RESULTS: All patients were treated with definitive chemoradiation
      (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were
      associated with earlier year of diagnosis and higher-grade tumors (P < 0.05).The
      overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors
      (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated
      with a reduced pCR rate (odds ratio 0.65, 95% confidence interval 0.43-0.96) with
      multivariable analysis. The 5-year survival for patients with pCR was 93%
      compared with 73% without it (<0.001). CONCLUSION: Microsatellite instability was
      independently associated with a reduction in pCR for locally advanced rectal
      cancer after neoadjuvant chemoradiation in this NCDB-based analysis.

PMID- 30216220
TI  - Surgical Transgastric Necrosectomy for Necrotizing Pancreatitis: A Single-stage
      Procedure for Walled-off Pancreatic Necrosis.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of surgical
      transgastric necrosectomy (TGN) for walled-off pancreatic necrosis (WON) in
      selected patients. BACKGROUND: WON is a common consequence of severe pancreatitis
      and typically occurs 3 to 5 weeks after the onset of acute pancreatitis. When
      symptomatic, it can require intervention. METHODS: A retrospective review of
      patients with WON undergoing surgical management at 3 high-volume pancreatic
      institutions was performed. Surgical indications, intervention timing, technical
      methodology, and patient outcomes were evaluated. Patients undergoing
      intervention <30 days were excluded. Differences across centers were evaluated
      using a P value of <0.05 as significant. RESULTS: One hundred seventy-eight total
      patients were analyzed (mean WON diameter = 14 cm, 64% male, mean age = 51 years)
      across 3 centers. The majority required inpatient admission with a median
      preoperative length of hospital stay of 29 days (25% required preoperative
      critical care support). Most (96%) patients underwent a TGN. The median duration
      of time between the onset of pancreatitis symptoms and operative intervention was
      60 days. Thirty-nine percent of the necrosum was infected. Postoperative
      morbidity and mortality were 38% and 2%, respectively. The median postoperative
      length of hospital length of stay was 8 days, with the majority of patients
      discharged home. The median length of follow-up was 21 months, with 91% of
      patients having complete clinical resolution of symptoms at a median of 6 weeks.
      Readmission to hospital and/or a repeat intervention was also not infrequent
      (20%). CONCLUSION: Surgical TGN is an excellent 1-stage surgical option for
      symptomatic WON in a highly selected group of patients. Precise surgical
      technique and long-term outpatient follow-up are mandatory for optimal patient
      outcomes.

PMID- 30216222
TI  - Variation in Surgical Treatment of Abdominal Aortic Aneurysms With Small Aortic
      Diameters in the Netherlands.
AB  - OBJECTIVE: To evaluate reasons to deviate from aneurysm diameter thresholds, and
      focus on the difference in how Dutch vascular surgical units (VSUs) perceive
      their deviation and their actual deviation. BACKGROUND: Guidelines recommend
      surgical treatment for asymptomatic abdominal aortic aneurysms (AAAs) with a
      diameter of at least 55 mm for men and 50 mm for women. We evaluate reasons to
      deviate from these guidelines, and focus on the difference in how Dutch vascular
      surgical units (VSUs) perceive their deviation and their actual deviation.
      METHODS: All patients undergoing elective AAA repair between 2013 and 2016
      registered in the Dutch Surgical Aneurysm Audit (DSAA) were included. Surgery at
      diameters of <55 mm for men and <50 mm for women were considered guideline
      deviations. National deviation and hospital variation in deviation were evaluated
      over time. Questionnaires were distributed among all Dutch VSUs, inquiring for
      acceptable reasons for guideline deviation. VSUs were asked to estimate the
      guideline deviation percentage in their hospital which was then compared with
      their DSAA percentage. RESULTS: In all, 9039 patients were included. In 15%, we
      found guideline deviation, varying from 2% to 40% between VSUs. Over time, 21
      VSUs were identified with a lower percentage of deviation than the national mean
      each year and 8 VSUs with a higher percentage. 44/60 VSUs completed the
      questionnaire. Most commonly reported reasons to deviate were concomitant large
      iliac diameter (91%) and saccular aneurysm (82%). The majority of the VSUs (77%)
      estimated their guideline deviation to be <5%. Eleven VSUs (25%) estimated their
      deviation concordant with their DSAA percentage, but 75% of VSUs underestimated
      their deviation. CONCLUSIONS: Dutch VSUs regularly deviate from the guidelines
      regarding aneurysm diameter, with variation between VSUs. Consensus exists
      amongst VSUs on acceptable reasons for guideline deviations; however, the
      majority underestimates their actual deviation percentage.

PMID- 30216224
TI  - Invited Editorial LAP-VEGaS Practice Guidelines for Video-based Education in
      Surgery: Content is Just the Beginning.

PMID- 30216225
TI  - Editorial: US FDA Breast Implant Postapproval Studies-Long-term Outcomes in
      99,993 Patients.

PMID- 30216223
TI  - Surgical Outcomes of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: A
      Korea-Japan Multicenter Study.
AB  - OBJECTIVE: To identify optimal surgical methods and the risk factors for long
      term survival in patients with hepatocellular carcinoma accompanied by
      macroscopic bile duct tumor thrombus (BDTT). SUMMARY BACKGROUND DATA: Prognoses
      of patients with hepatocellular carcinoma accompanied by BDTT have been known to
      be poor. There have been significant controversies regarding optimal surgical
      approaches and risk factors because of the low incidence and small number of
      cases in previous reports. METHODS: Records of 257 patients from 32 centers in
      Korea and Japan (1992-2014) were analyzed for overall survival and recurrence
      rate using the Cox proportional hazard model. RESULTS: Curative surgery was
      performed in 244 (94.9%) patients with an operative mortality of 5.1%. Overall
      survival and recurrence rate at 5 years was 43.6% and 74.2%, respectively. TNM
      Stage (P < 0.001) and the presence of fibrosis/cirrhosis (P = 0.002) were
      independent predictors of long-term survival in the Cox proportional hazards
      regression model. Both performing liver resection equal to or greater than
      hemihepatectomy and combined bile duct resection significantly increased overall
      survival [hazard ratio, HR = 0.61 (0.38-0.99); P = 0.044 and HR = 0.51 (0.31
      0.84); P = 0.008, respectively] and decreased recurrence rate [HR = 0.59 (0.38
      0.91); P = 0.018 and HR = 0.61 (0.42-0.89); P = 0.009, respectively].
      CONCLUSIONS: Clinical outcomes were mostly influenced by tumor stage and
      underlying liver function, and the impact of BDTT to survival seemed less
      prominent than vascular invasion. Therefore, an aggressive surgical approach,
      including major liver resection combined with bile duct resection, to increase
      the chance of R0 resection is strongly recommended.

PMID- 30216226
TI  - The effect of traditional Chinese medicine Zhike-Houpu herbal pair (ZKHPHP) on
      depressive behaviors and hippocampal serotonin 1A receptors in rats following
      chronic unpredictable mild stress (CUMS).
AB  - OBJECTIVE: Zhike-Houpu herbal pair (ZKHPHP) is a well-known Chinese medicine to
      treat gastrointestinal motility dysfunction. Recently, many researchers have
      found that some of the compounds of ZKHPHP such as meranzin hydrate and magnolol
      have antidepressant effects. However, little is known about the antidepressant
      mechanism of ZKHPHP. Therefore, the main aim of the study is to evaluate the
      antidepressant-like effects of ZKHPHP and its possible mechanism of action on
      HTR1A (5-hydroxytryptamine receptor 1A) in the hippocampus CA1 region in rats
      exposed to chronic unpredictable mild stress. METHODS: Male Sprague Dawley (SD)
      rats were randomly divided into six groups: Normal, Model, ZKHPHP(3g/kg),
      ZKHPHP(10g/kg), ZKHPHP(20g/kg) and ZKHPHP(30g/kg); N=8 per group. We exposed the
      rats to chronic unpredictable mild stress (CUMS) and then assessed antidepressant
      like effects of ZKHPHP by measuring weight change, observing the open-field test
      and measuring sucrose water consumption. The antidepressant mechanism was
      examined by measuring the effect of ZKHPHP on HTR1A protein expression and HTR1A
      mRNA expression in the hippocampus CA1 region by using immunohistochemistry
      analysis, western blotting, and Real-time RT-PCR. RESULTS: ZKHPHP (10 or 20g/kg)
      reduced the incidence of depressive-like behaviors and increased HTR1A protein
      and HTR1A mRNA expression in the hippocampus CA1 in rats displaying depressive
      behavior, while ZKHPHP (3 or 30g/kg) had no obvious effect on the measured
      depression indicators. CONCLUSIONS: These data show that ZKHPHP has
      antidepressant-like effects based on a CUMS-induced depression model in rats.
      ZKHPHP may be attractive as an antidepressant because of its beneficial effects
      on depression and the absence of gastrointestinal dysregulation, which is a
      frequently observed unintended effect of many commonly used antidepressive
      medications.

PMID- 30216227
TI  - Autophagy Induction Ameliorates Inflammatory Responses in Intestinal Ischemia
      Reperfusion Through Inhibiting NLRP3 Inflammasome Activation.
AB  - Intestinal ischemia/reperfusion (I/R)-induced systemic inflammation leads to
      multiple organ dysfunction syndrome (MODS). Previous studies have indicated that
      the NLRP3 inflammasome modulates intestinal inflammation; however, the
      pathophysiological mechanisms remain unclear. Autophagy is a critical metabolic
      mechanism that promotes cellular survival following ischemic injury. Recently,
      basal autophagy has been implicated in the alleviation of extensive inflammation.
      However, the role of autophagy in NLRP3 inflammasome activation in intestinal I/R
      induced inflammatory injury remains undefined. In the present study, we examined
      whether NLRP3 inflammasome activation is induced in mice subjected to intestinal
      I/R injury, which is measured as increased ASC levels, caspase-1 activity and
      Interleukin-1beta (IL-1beta) secretion. Importantly, the in vitro results showed
      that NLRP3 knockdown decreases pro-inflammatory cytokine production and increases
      resistance to hypoxia/reoxygenation (H/R)-triggered inflammation. Subsequently,
      we demonstrated a critical role for autophagy in suppressing intestinal I/R
      induced NLRP3 inflammasome activation in vivo. Furthermore, we showed that the
      loss of autophagy activates inflammasome-mediated IL-1beta secretion, which
      aggravates H/R injury, and NLRP3 knockdown reverses these effects. Collectively,
      these results directly implicated the homeostatic process of autophagy and NLRP3
      inflammasome in ischemic bowel disease and identified a novel pathway for
      therapeutic intervention in intestinal I/R.

PMID- 30216228
TI  - Gallium 68-PSMA PET/CT for lesion characterization in suspected cases of prostate
      carcinoma.
AB  - OBJECTIVE: To assess the feasibility of gallium 68 (Ga)-prostate specific
      membrane antigen (PSMA) PET/computed tomography (CT) to identify patients who
      truly harbor clinically significant prostate cancer (PCa) in a cohort of patients
      with clinical and biochemical/radiological suspicion of PCa. PATIENTS AND
      METHODS: A total of 118 patients with suspected PCa who underwent Ga-PSMA PET/CT
      between May 2015 and June 2016 were prospectively included. Final decision on
      performing biopsy was left to the referring urologist after considering the
      clinical data, scan findings and discussion with the patient. RESULTS: Overall,
      51 patients were scan negative, among whom six underwent biopsy but was negative
      for malignancy. In 45 patients, an immediate biopsy could be avoided and put on
      follow-up. None of these patients were documented to have PCa in the short
      average follow-up of 6 months. Among 67 patients who were scan positive, 56
      patients underwent transrectal ultrasonography-guided biopsy, and malignancy
      could be documented in 46 of them. In addition, comprehensive initial staging
      information could be obtained in them, with organ-confined disease demonstrated
      in 33 patients and metastatic disease in 13 patients. CONCLUSION: Ga-PSMA PET/CT
      can act as a gate keeper in selecting patients with suspected PCa who should
      undergo an immediate transrectal ultrasonography-guided biopsy and who could be
      kept on active surveillance.

PMID- 30216229
TI  - A prospective study comparing 99mTc-MIBI and 99mTc-MDP with 99mTc-DTPA for lung
      ventilation scintigraphy in pulmonary thromboembolism.
AB  - OBJECTIVE: The aim of the study was to assess the efficacy of technetium 99m
      methyl diphosphonate (Tc-MDP) and technetium 99m-methoxyisobutylisonitrile (Tc
      MIBI) as radioaerosol alternatives to technetium 99m
      diethylenetriaminepentacetate (Tc-DTPA) in the evaluation of pulmonary
      thromboembolism, as the direct consequence of the possible outcome could be cost
      saving. PATIENTS AND METHODS: Patients referred to our institution from August
      2015 to July 2017 for a ventilation-perfusion scan who fulfilled the inclusion
      criteria were enrolled into the study as participants. Each ventilation agent was
      used to ventilate 43 participants, making a total of 129 participants in the
      study. Images were assessed for quality and alveolar clearance qualitatively and
      semiquantitatively correspondingly by a nuclear medicine physician blinded to the
      agent used. RESULTS: Tc-MIBI had higher count rates than Tc-DTPA and Tc-MDP, with
      a statistically significant difference when compared with Tc-DTPA (P=0.021). Tc
      MIBI clearly showed slower alveolar clearance when compared with the clearance of
      Tc-DTPA (P<=0.0001) and Tc-MDP (P<=0.001). In terms of image quality, Tc-MIBI
      generally had better quality images as compared with the other two radioaerosols,
      with a statistically significant difference when compared with Tc-DTPA (P=0.001).
      CONCLUSION: Tc-MIBI had superior image quality and slower alveolar clearance when
      compared with Tc-DTPA. Alongside Tc-MDP, these agents can replace Tc-DTPA
      whenever clinically and economically applicable.

PMID- 30216231
TI  - Measuring Community Prevalence of Trichomonas vaginalis Infection to Guide Local
      Screening Practices: A Process Improvement Project.
AB  - The CDC suggests screening for Trichomonas vaginalis infection might be
      considered in high prevalence populations. High asymptomatic infection rates and
      poor sensitivity of clinical diagnosis make it difficult to estimate local
      prevalence. Testing of ThinPrep samples can provide an estimate of local
      Trichomonas vaginalis infection rates and guide screening practices.

PMID- 30216230
TI  - Dual-time 18F-FDG PET/CT for the detection of liver metastases in breast cancer.
AB  - OBJECTIVE: The aim was to investigate the diagnostic potential of dual-time-point
      F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG
      PET/CT) in patients with breast cancer with known or suspected liver metastases
      and to assess its clinical value on clinical management. PATIENTS AND METHODS: A
      total of 151 consecutive patients with breast cancer who underwent F-FDG PET/CT
      scan for staging or restaging, in whom an additional delayed scan of the liver
      was performed, were retrospectively evaluated. RESULTS: Overall, F-FDG PET/CT
      showed the presence of 146 liver metastases in 57 patients. Overall, 54 of these
      lesions were clearly identified at standard whole-body acquisition, 49 were
      suspected and 43 were missed in early acquisition. Only 59.6% of patients with
      liver involvement were clearly identified at the first scan. A high percentage of
      patients (48.3%) showed at least one liver lesion suspected on standard
      acquisition which was not more confirmed in late scan. Maximum tumour
      standardized uptake value of liver metastases was significantly higher in delayed
      as compared with standard acquisition (6.5+/-2.4 vs. 5.3+/-1.6; P<0.0001). The
      higher detection rate in late acquisition altered patient management in a
      relative low number of cases in the whole series (15.8%) and in a higher
      proportion (28.6%) in the group of patients with exclusive liver involvement.
      CONCLUSION: The results of the study revealed the potential usefulness of late
      liver acquisition in patients with breast cancer with suspected or known liver
      metastases. Its use should be advocated in case of inconclusive results on
      standard acquisition to improve the study interpretation confidence or to
      increase the accuracy in specific clinical settings.

PMID- 30216232
TI  - The Frequency of Discordant Gyrase A Genotypes Among Cases of Multiple Neisseria
      gonorrhoeae Infections at Different Anatomic Sites.

PMID- 30216233
TI  - Reconstruction of the Alveolar Bone Using Bone Augmentation With Selective Laser
      Melting Titanium Mesh Sheet: A Report of 2 Cases.
AB  - Bone augmentation is used to supplement bone defects during dental implant
      treatment. In this technique, the area filled with bone prosthetic material is
      covered with an artificial space-making device or titanium mesh sheet, which must
      be manually adapted to the bone defect during the procedure before being fixed in
      place. Selective laser melting (SLM) method can be used to preadapt the titanium
      mesh sheet based on preoperative CT data. This method enables shorter surgery
      times compared with conventional titanium mesh sheet methods, as well as
      regeneration of an ideal alveolar bone shape. Here, we present 2 cases of bone
      augmentation using the SLM titanium mesh sheet method. The postoperative course
      was without complications in both cases; neither patient experienced mesh
      exposure or infection during healing. The SLM titanium mesh sheet method should
      be considered as a new and effective bone augmentation method.

PMID- 30216234
TI  - Classic animal models of Parkinson's disease: a historical perspective.
AB  - The quest to better understand the pathophysiology of Parkinson's disease (PD)
      and to find new therapies to provide greater relief to affected patients
      continues. The use of animal models of PD has been invaluable in the process.
      Here, we review, through a historical lens, some of the contribution of the 6
      hydroxydopamine-lesioned rat and of the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-lesioned nonhuman primate, in refining our understanding of PD
      and its treatment-related complications. We examine the mechanisms underlying the
      toxicity of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,
      and then explore some of the advances at the molecular, pharmacological,
      electrophysiological and surgical levels made while experimenting on these animal
      models. We also discuss behavioural testing that can be performed with these
      animal models and highlight some of their limitations.

PMID- 30216236
TI  - Against empathy: The case for rational compassion.

PMID- 30216237
TI  - Individual Variability in Waist Circumference and Body Weight in Response to
      Exercise.
AB  - PURPOSE: To determine the magnitude of exercise-induced individual variability
      for waist circumference (WC) and body weight change after accounting for
      biological variability and measurement error. Determinants of response
      variability were also considered. METHODS: Participants (53 +/- 7.5 years) were
      181 (61% women) adults with abdominal obesity randomized to: control; low amount,
      low intensity (LALI); high amount, low intensity (HALI); or high amount, high
      intensity exercise (HAHI) for 24 weeks. Unstructured physical activity was
      measured by accelerometer. The variability in response to exercise for WC and
      body weight (SDR) was isolated by subtracting the standard deviations for the
      change scores in the exercise group from that of the control group. RESULTS: The
      variability of response due to exercise (SDR) for change in WC was 3.1, -0.3 and
      3.1 cm for LALI, HALI and HAHI groups, respectively. Corresponding values for
      body weight were 3.8, 2.0 and 3.5 kg for LALI, HALI and HAHI, respectively. The
      high amount exercise groups yielded the highest proportion of individuals with a
      clinically meaningful response. No variables predicted the response to exercise
      (p>0.05). CONCLUSIONS: Substantial variability in response to standardized
      exercise was observed for change in both WC and body weight after accounting for
      the variability not attributed to exercise. Potential determinants of the
      interindividual variability in response to exercise remain unclear.

PMID- 30216238
TI  - Fitness Mediates Activity and Sedentary Patterns Associations with Adiposity in
      Youth.
AB  - PURPOSE: We aimed to examine the cross-sectional associations of patterns of
      sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) with total
      fat mass index (FMI) and abdominal fat mass index (FMIabd) in children, and
      additionally, to analyze if cardiorespiratory fitness (CRF) mediated these
      associations. METHODS: FMI and FMIabd were assessed with DXA in 333 participants
      (172 girls) aged 9-11 years. MVPA, ST, breaks in sedentary time per sedentary
      hour (BST/ST) and the number of daily sedentary bouts with various lengths (1-4,
      5-9, 10-14, and >=15 minutes) were assessed with accelerometry and CRF using a
      maximal cycle test. Hayes' PROCESS macro for SPSS was used for mediation
      analysis. RESULTS: The number of shorter sedentary bouts (1-4 minutes) was
      inversely associated with FMI (beta =-0.108), whereas longer sedentary bouts (5-9
      minutes, beta=0.169; 10-14 minutes, beta=0.193; >=15 minutes, beta=0.377) had a
      positive association, independent of MVPA (p<0.05). A similar trend was found for
      FMIabd. MVPA was negatively related to FMI (beta=-0.029) and to FMIabd (beta=
      0.003). There were no main associations for ST and BST/ST (p>0.05). CRF was
      inversely related to total and abdominal adiposity, and a large portion (40.9
      65.7%) of the associations of MVPA and sedentary bouts with both FMI and FMIabd
      were mediated by CRF. CONCLUSION: Time in MVPA and accumulating ST in shorter
      sedentary bouts is inversely related to adiposity. However, these associations
      may be mediated by CRF. Emphasis should be given to programs that target
      increases in MVPA, which may influence CRF while reducing sedentary recreational
      behaviors.

PMID- 30216239
TI  - Effects of Sprint-Interval and Endurance Respiratory Muscle Training Regimens.
AB  - INTRODUCTION: Recently a novel, time-saving respiratory muscle sprint-interval
      training (RMSIT) was developed. To test the extent to which RMSIT improves
      respiratory muscle performance compared to a conventional respiratory muscle
      endurance training (RMET), a novel incremental respiratory muscle test (IncRMT),
      loading inspiratory and expiratory muscles, was designed to assess performance
      changes associated with respiratory muscle training (RMT). METHODS: Healthy,
      moderately trained males and females (age: 26 +/- 5years, V[Combining Dot
      Above]O2peak: 47 +/- 12 ml.min.kg) were randomized and balanced to 3 groups
      (RMSIT 5m/5f; RMET 6m/6f; PLAT 5m/6f). Lung function, respiratory muscle strength
      and IncRMT performance were tested before and after one month of RMT. During the
      IncRMT, muscle activity and muscle deoxygenation were assessed via surface
      electromyography and near-infrared spectroscopy of sternocleidomastoid (STERNO),
      intercostal (INTER) and abdominal (ABDO) muscles. RESULTS: Two-way ANOVA revealed
      a main effect of training for increased maximal voluntary ventilation (P = 0.001)
      and maximal inspiratory pressure (P = 0.017). Both RMT groups increased work of
      breathing during training sessions to the same extent (RMSIT: +17.4 +/- 8.9kJ,
      RMET: +26.2 +/- 16.1kJ; P = 0.143) with a larger increase in average mouth
      pressure in RMSIT (RMSIT: +20.0 +/- 15.0cmH2O, RMET: +3.3 +/- 1.5cmH2O; P =
      0.001). After training, IncRMT duration increased in both RMT groups compared to
      PLAT (RMSIT: +5.6 +/- 2.1min; P = 0.0006 vs. PLAT; RMET: +3.8 +/- 4.2min; P =
      0.020 vs. PLAT). At similar work, only INTER activity during inspiration
      increased following RMET. Higher performance following RMSIT was associated with
      higher activity in STERNO and ABDO, while following RMET, STERNO, INTER and ABDO
      showed higher activity. CONCLUSION: One month of RMSIT and RMET show similar
      improvements in respiratory muscle performance despite different duration of
      training sessions. Also, muscular adaptations might differ.

PMID- 30216240
TI  - Esmolol, Antinociception, and Its Potential Opioid-Sparing Role in Routine
      Anesthesia Care.
AB  - beta-Adrenergic blockade is an important mechanism for reducing morbidity and
      mortality in patients with hypertension and heart failure. Esmolol has been used
      widely for its chronotropic and antihypertensive effects. However, there has been
      recent inquiry regarding perioperative esmolol use and nociceptive modulation.
      Conventional postoperative analgesic treatment has relied primarily on opioids,
      which present their own adverse effects and pharmacoepidemiologic repercussions.
      Esmolol, to date, has not shown any direct analgesic or anesthetic properties;
      however, recent studies suggest that esmolol may have antinociceptive and
      postoperative opioid-sparing effects. In this Daring Discourse narrative, we
      describe the role of esmolol in current perioperative beta-blockade guidelines
      (related to noncardiac surgery), briefly describe studies supporting the
      antinociceptive effects of esmolol, propose mechanisms for esmolol
      antinociception, and forecast potential routine esmolol use intraoperatively (as
      part of a multimodal total intravenous anesthetic) and its effects on opioid
      sparing. The reading audience of regional anesthesiologists and acute pain
      medicine physicians is uniquely positioned to take a lead role in promulgating
      this care advance amid (i) the unwanted effects of the opioid epidemic and (ii)
      the uncertain notion of whether routine general anesthesia care (with fentanyl)
      may indirectly be contributing to the epidemic.

PMID- 30216241
TI  - Tendon Transfer Options for Trapezius Paralysis: A Biomechanical Study.
AB  - INTRODUCTION: The purpose of this study was to evaluate the biomechanical
      effectiveness regarding scapulothoracic (ST) upward rotation of two different
      tendon transfer procedures involving the levator scapulae, rhomboid major, and
      rhomboid minor to restore the function of the paralyzed trapezius. METHODS: Six
      fresh frozen hemithoraces were mounted on a custom-built apparatus. A three
      dimensional electromagnetic tracking system was used to record ST upward/downward
      rotation of the (1) normal trapezius, levator scapulae, rhomboid minor, and
      rhomboid major; (2) Eden-Lange (EL) transferl and (3) a modified EL transfer
      (triple transfer). RESULTS: The normal trapezius was found to be an upward
      rotator of the scapula and led to a mean ST rotation angle of 26.98 degrees .
      Similarly, the modified triple transfer led to an upward rotation of the scapula,
      with a mean ST rotation angle of 22.23 degrees , whereas the EL led to an initial
      downward rotation of the scapula to -6.69 degrees , with a mean scapulothoracic
      displacement angle of 1.13 degrees . DISCUSSION: The upward rotation of the
      scapula from the modified transfer mimicked the function of the normal trapezius
      better than did the traditional EL transfer. LEVEL OF EVIDENCE: Level V,
      biomechanical study.

PMID- 30216243
TI  - Patient Outcomes After Revision of Anatomic Total Shoulder Arthroplasty to
      Reverse Shoulder Arthroplasty for Rotator Cuff Failure or Component Loosening: A
      Matched Cohort Study.
AB  - PURPOSE: To compare outcomes after conversion of anatomic total shoulder
      arthroplasty (aTSA) to reverse total shoulder arthroplasty (RTSA) and a matched
      cohort. METHODS: Patients converted from aTSA to RTSA for rotator cuff failure or
      component loosening and a primary RTSA matched cohort were retrospectively
      identified from a prospective database. Demographics and preoperative and
      postoperative outcomes were obtained and compared. RESULTS: Age, sex, body mass
      index, follow-up length, and preoperative function were similar between revision
      (n = 35) and primary (n = 70) groups. At final follow-up, visual analog scale
      pain (2.4 +/- 2.8 versus 1.7 +/- 2.8; P = 0.24) and American Shoulder and Elbow
      Surgeons (68 +/- 26 versus 76 +/- 24; P = 0.14) scores were similar. The revision
      group had worse subjective shoulder value scores (63 +/- 30 versus 79 +/- 21; P =
      0.002), satisfaction (74% versus 90%; P = 0.03), and more complications (31%
      versus 13%; P = 0.02). CONCLUSION: Revision of aTSA to RTSA for component
      loosening or rotator cuff failure results in function comparable to primary RTSA;
      however, more complications, worse subjective shoulder value scores, and lower
      patient satisfaction should be expected. LEVEL OF EVIDENCE: Level III,
      retrospective comparative.

PMID- 30216242
TI  - Using Patient-reported Outcomes Measurement Information System Measures to
      Understand the Relationship Between Improvement in Physical Function and
      Depressive Symptoms.
AB  - INTRODUCTION: This investigation determined whether improved physical function
      and decreased pain would reduce depressive symptoms using the Patient-reported
      Outcomes Measurement Information System (PROMIS). METHODS: This cohort study
      analyzed PROMIS Depression, Physical Function, and Pain Interference CAT scores
      from 3,339 patients presenting to a tertiary orthopaedic center. Patients
      demonstrating at least a-five point (effect size, 0.5) improvement in PROMIS
      Physical Function between consecutive visits were eligible for inclusion.
      RESULTS: Patients presented, on average, with Physical Function and Pain
      Interference scores nearly one SD worse than population averages and Depression
      scores that approximated the normal population. Improved Physical Function and
      Pain Interference scores demonstrated no correlation with change in Depression
      scores (r = -0.13; r = 0.25). CONCLUSION: Substantial early improvement in PROMIS
      Physical Function scores is not associated with change in PROMIS Depression
      scores. PROMIS Depression scores likely reflect underlying mental health rather
      than situational depressive symptoms. LEVEL OF EVIDENCE: Prognostic, level III.

PMID- 30216244
TI  - Median Nerve Ultrasonography Measurements Correlate With Electrodiagnostic Carpal
      Tunnel Syndrome Severity.
AB  - INTRODUCTION: The purpose of this study was to assess whether median nerve
      ultrasonography (US) measurements correlate with the severity scale of
      electrodiagnostic studies (EDS) of carpal tunnel syndrome (CTS). METHODS: A
      retrospective review was conducted of patients aged >=18 years who underwent both
      median nerve US and EDS. US measurements of the median nerve cross-sectional area
      at the distal wrist crease and forearm were used to calculate the median nerve
      wrist-to-forearm ratio. EDS severity was classified according to guidelines from
      the American Association of Electrodiagnostic Medicine. RESULTS: A total of 112
      wrists (n = 112) in 78 consecutive patients with a mean age of 59 (range, 26 to
      88) years were included. Increased cross-sectional area at the distal wrist
      crease and wrist-to-forearm ratio were significantly correlated with increased
      EDS severity (P < 0.0001). DISCUSSION: Median nerve US measurements not only
      distinguished between normal and abnormal EDS but also correlated with the
      category of EDS severity. LEVEL OF EVIDENCE: Diagnostic III.

PMID- 30216245
TI  - A Comparison of Geriatric Hip Fracture Databases.
AB  - INTRODUCTION: The National Surgical Quality Improvement Project (NSQIP) and the
      Trauma Quality Improvement Project (TQIP) collect data on geriatric hip fractures
      (GHFs) that could be used to generate risk-adjusted metrics for care of these
      patients. We examined differences between GHFs reported by our own trauma center
      to the NSQIP and TQIP and those vetted through an internal GHF list. METHODS: We
      reviewed charts of GHFs treated between January 1 and December 31, 2015, and
      compared patients in an internal GHF database and/or reported to the NSQIP and/or
      TQIP and determined differences between databases. RESULTS: We identified 89
      "true" GHFs, of which 96% were identified by our institutional database, 70% by
      NSQIP, and 9% by the TQIP. No differences were found in outcomes and total costs.
      The net revenue/patient in the NSQIP database was $24,373 more than those in the
      institutional database. CONCLUSION: Caution should be taken when using NSQIP/TQIP
      databases to evaluate the care of GHFs. LEVEL OF EVIDENCE: Level III.

PMID- 30216246
TI  - C5 Motor Palsy After Single- and Multi-level Anterior Cervical Diskectomy and
      Fusion: A Retrospective Review.
AB  - INTRODUCTION: Postoperative C5 nerve root palsy is a known complication after
      cervical surgery. The effect of increasing number of levels fused on the
      prevalence of C5 palsy after anterior cervical diskectomy and fusion (ACDF) is
      unclear. METHODS: Medical records of ACDF patients that included the C4-5 level
      at one institution were retrospectively reviewed. C5 palsy was defined as motor
      decline of the deltoid and/or biceps brachii muscle function by at least 1 level
      on standard manual muscle testing. RESULTS: A total of 196 patients met the
      inclusion criteria, with no significant differences noted between groups
      undergoing single- or multi-level ACDF. The overall C5 palsy rate was 5.1%. Palsy
      rates were not statistically significant based on the number of levels fused. Six
      of the 10 patients with C5 palsy had complete recovery of motor strength, whereas
      2 patients had at least some level of strength recovery. CONCLUSION: The overall
      C5 palsy rate was 5.1% for all patients undergoing up to four-level ACDF. The
      rate of postoperative motor decline was lowest in the patients undergoing two
      level ACDF and highest in the single-level group, but this finding did not reach
      statistical significance. The prognosis for strength recovery by final follow-up
      is excellent. LEVEL OF EVIDENCE: Level III, Case-control.

PMID- 30216247
TI  - Correlation of Short Knee Radiographs and Full-length Radiographs in Patients
      Undergoing Total Knee Arthroplasty.
AB  - INTRODUCTION: The clinical success and longevity of a primary total knee
      arthroplasty (TKA) in large part depend on our ability to control coronal
      alignment. However, controversy exists regarding which radiographs to use for the
      most accurate interpretation. The study assesses the accuracy of coronal
      alignment measurements using a single short knee radiograph (SKR) in comparison
      with full-length radiographs (FLRs). METHODS: Using our institutional database,
      we retrieved radiographs of all patients who have had pre- and postoperative FLRs
      for their primary TKA in 2014. The following measurements were obtained on both
      short and long radiographs: femoral-tibial angle (FTA), anatomic lateral distal
      femoral angle, medial proximal tibial angle, condylar-plateau angle, and condylar
      plateau distance. A reliability analysis was conducted between the pre- and
      postoperative SKRs and FLRs using the intraclass correlation coefficient (ICC).
      RESULTS: Radiographs of 236 limbs were included in the analysis. The FTA showed
      an ICC of 0.84 and 0.69 on the pre- and postoperative radiographs, respectively.
      Good ICC was seen in the lateral distal femoral angle in both the pre- and
      postoperative radiographs; these were 0.70 and 0.67, respectively. Also, the
      medial proximal tibial angle showed good to excellent correlation, with an ICC of
      0.83 on the preoperative and 0.66 on the postoperative radiographs. CONCLUSION:
      This study illustrates that SKRs could be an appropriate substitute for FLRs for
      the evaluation of primary TKA coronal alignment, especially in the postoperative
      assessment of these patients. LEVEL OF EVIDENCE: Level III.

PMID- 30216248
TI  - Monitoring the External and Internal Load Under 2 Teaching Methodologies.
AB  - Gonzalez-Espinosa, S, Antunez, A, Feu, S, and Ibanez, SJ. Monitoring the external
      and internal load under 2 teaching methodologies. J Strength Cond Res XX(X): 000
      000, 2018-The purpose of this study was to analyze and compare the physical
      demands produced by the implementation of 2 sport teaching methods during a class
      and their relation with the learning achieved by the students. Two intervention
      programs were used to teach the sport of basketball, one based on the direct
      instruction (DI) method and the other on the tactical-game approach (TGA). The
      intervention programs were administered to 4 groups of students, 2 for each
      methodology, with 88 students participating in the study. A total of 10 practical
      sessions were given, as well as a pre-test and post-test. The practical sessions
      and the tests were recorded with an inertial system for monitoring and recording
      physical activity and movement in real time. Differences were found between the
      methodologies in the teaching sessions in the variables m.min, acc.min, PL.min,
      and HRmax (p < 0.000). In the assessment tests, there were also differences
      between both methodologies in the walk and sprint variables (p < 0.005). The
      results obtained from the analysis of the sessions using each methodology show
      that the TGA method obtained better results in the variables of external and
      internal loads than the DI methodology. The TGA methodology permitted a greater
      development of the students' physical fitness. Moreover, performance in play was
      not associated with the achievement of higher values in the results of external
      and internal load in the tests. The students trained with the TGA methodology
      recorded better performance indicators in the game. These results lead us to
      recommend physical education teachers to use a student-centered approach in their
      lessons because it improved both the students' physical fitness and their sports
      performance.

PMID- 30216249
TI  - Use of Functional Movement Screen Scores to Predict Dynamic Balance in Physically
      Active Men and Women.
AB  - Scudamore, EM, Stevens, SL, Fuller, DK, Coons, JM, and Morgan, DW. Use of
      functional movement screen scores to predict dynamic balance in physically active
      men and women. J Strength Cond Res XX(X): 000-000, 2018-The primary focus of this
      study was to determine whether scores obtained from the Functional Movement
      Screen (FMS) can predict dynamic balance in young, healthy adults. Thirty-four
      physically active participants completed the FMS, and balance was assessed using
      measures of composite reach (CR) distance and overall stability indices (OSI)
      derived from Y Balance and Biodex Balance System testing, respectively. Results
      indicated that higher overall FMS scores were associated with better CR and OSI,
      and participants with FMS composite scores greater than 14 exhibited better CR
      compared to those with composite scores less than or equal to 14. In addition,
      lasso penalized regression demonstrated that (a) scores of 2 on the deep squat
      and 3 on the trunk stability push-up movements predicted a greater CR and (b)
      higher shoulder mobility scores and a rotary stability score of 3 predicted
      better OSI. We conclude that dynamic balance in young, active men and women can
      be predicted by specific FMS item scores.

PMID- 30216250
TI  - Grip Strength in Youth Ice Hockey Players: Normative Values and Predictors of
      Performance.
AB  - Toong, T, Wilson, KE, Urban, K, Paniccia, M, Hunt, AW, Keightley, M, and Reed, N.
      Grip strength in youth ice hockey players: Normative values and predictors of
      performance. J Strength Cond Res 32(12): 3503-3511, 2018-Grip strength is a
      simple, valid, and reliable tool for estimating overall muscular strength, a key
      component of health-related fitness and sport performance. To date, there is a
      paucity of up-to-date and developmentally sensitive grip strength norms specific
      to youth-athlete populations. The objectives of this study are to (a) establish
      normative grip strength values in youth ice hockey players, (b) descriptively
      compare these values with existing Canadian pediatric norms, and (c) explore the
      relationship between age, sex, body mass, and hockey playing level on grip
      strength performance. A sample of 690 male and female youth ice hockey players
      between the ages of 10 and 16 years were included. Participants completed
      assessments of maximal grip strength using a hand dynamometer on both hands. In
      addition, age, sex, body mass, and hockey playing level were collected. Maximal
      absolute grip strength, stratified by age and sex, was higher than previously
      published Canadian pediatric norms. Grip strength increased with age in both
      sexes. Males and females performed similarly until 12 years of age, after which
      point males had greater strength. Individuals with greater body mass had greater
      strength. For the nondominant hand, competitive players had greater strength than
      those playing house league or select. This study describes normative grip
      strength values in youth ice hockey players according to age, sex, body mass, and
      playing level. These athlete-specific norms may be used to help evaluate and
      monitor changes in grip strength over time in youth ice hockey players.

PMID- 30216251
TI  - Comparison of Physical Fitness Parameters for Starters vs. Nonstarters in an NCAA
      Division I Men's Lacrosse Team.
AB  - Sell, KM, Prendergast, JM, Ghigiarelli, JJ, Gonzalez, AM, Biscardi, LM, Jajtner,
      AR, and Rothstein, AS. Comparison of physical fitness parameters for starters vs.
      nonstarters in an NCAA division I men's lacrosse team. J Strength Cond Res XX(X):
      000-000, 2018-The purpose of this study was to present a fitness profile of
      Division I male lacrosse players and compare the fitness attributes across
      different positions and starting status. Forty-one Division I men's lacrosse
      players (19.6 +/- 1.6 years, 82.5 +/- 9.5 kg, 182.0 +/- 5.4 cm) volunteered to
      participate in the study. Fitness attributes assessed included aerobic fitness
      (1.5-mile run), muscular strength (1 repetition maximum bench press, squat, and
      hang clean), grip strength (hand dynamometer), explosive power (vertical jump),
      agility (3-cone drill, pro-agility), body composition (7-site skinfold), and
      speed (20- and 40-yard sprint). All testing was conducted by a certified strength
      and conditioning coach and occurred at the conclusion of pre-season training. The
      only significant difference across positions was for body mass, whereby
      defensemen were significantly heavier than attacking players (p < 0.05). Starters
      were significantly faster on the 3-cone drill, 20- and 40-yard sprint, and jumped
      significantly higher on the vertical jump compared with nonstarters (p < 0.05).
      Attributes pertaining to anaerobic fitness (speed, agility, and explosive power)
      may be better predictors of starting status than aerobic fitness in men's NCAA
      Division I lacrosse players. This differs from previous research on men's club
      lacrosse players where a difference in aerobic fitness and body composition was
      shown between starters and nonstarters. The normative data presented in this
      study may assist strength and conditioning coaches in the development of sport
      specific training programs and motivate athletes toward achieving sport-specific
      fitness goals by helping identify areas of weakness before the start of the
      season.

PMID- 30216252
TI  - Monitoring Wellness, Training Load, and Running Performance During a Major
      International Female Field Hockey Tournament.
AB  - McGuinness, McMahon, G, A, Malone, S, Kenna, D, Passmore, D, and Collins, K.
      Monitoring wellness, training load, and running performance during a major
      international female field hockey tournament. J Strength Cond Res XX(X): 000-000,
      2018-The current observational study quantified players' activity profiles during
      a major international female field hockey tournament and determined whether an
      association exists between well-being measures and running performance within
      elite female hockey players. Elite female field hockey players (23 +/- 3 years;
      162.6 +/- 13 cm; and 66 +/- 6 kg) participated in the study. Participants running
      performance was monitored using global positioning system technology (S5;
      Catapult Innovations, Scoresby, Victoria, Australia), with daily well-being
      questionnaires used to quantify player responses during the tournament.
      Thresholds for the magnitude of the observed change for each variable were
      determined using the Hopkins Spreadsheets for analysis of controlled trials.
      Relative distance (m.min) was likely lower when compared with game 1 in game 7.
      Relative high speed (m.min >16 km.h) was likely lower in games 5, 6, and 7 when
      compared with game 1. Subjective load was very likely higher in game 2 and very
      likely lower in game 3 when compared with game 1. Mood and sleep quality were
      likely lower in game 1 when compared with game 4 and game 7. Muscle soreness was
      likely higher when compared with game 1 in game 7. During the tournament, it was
      observed that a decrease in players' daily well-being was accompanied by changes
      in running performance. Furthermore, changes to players' muscle soreness and
      sleep quality result in decreased players' high-speed running performance during
      match-play. Therefore, to prevent the observed effects, coaches should adopt
      strategies to enhance sleep quality and incorporate specific recovery modalities
      to reduce musculoskeletal soreness.

PMID- 30216253
TI  - Lumbopelvic-Hip Complex and Scapular Stabilizing Muscle Activations During Full
      Body Exercises With and Without Resistance Bands.
AB  - Wasserberger, KW, Downs, JL, Barfield, JW, Williams, TK, and Oliver, GD.
      Lumbopelvic-hip complex and scapular stabilizing muscle activations during full
      body exercises with and without resistance bands. J Strength Cond Res XX(X): 000
      000, 2018-Inefficient sequencing in the kinetic chain has been linked to
      decreased performance and increased injury risk. Resistance band usage is very
      common in baseball/softball due to accessibility and low cost. However,
      resistance band use has primarily focused on the rotator cuff and surrounding
      shoulder musculature, thereby ignoring the rest of the kinetic chain. Currently,
      it is unclear whether resistance bands are effective tools for training
      musculature outside the throwing extremity. Thus, the purpose of this study was
      to examine muscle activations of the lumbopelvic-hip complex (LPHC) and scapular
      stabilizing musculature during 4 full-body exercises with and without the use of
      a resistance band. Twenty healthy, active individuals (174.39 +/- 1.58 cm; 74.10
      +/- 1.75 kg; 21.85 +/- 1.13 years) participated. Data were collected through
      surface electromyography for the LPHC and scapular stabilizing musculature during
      4 full-body exercises with and without a resistance band. Statistical analyses
      were used to determine significant differences in activation levels between
      exercises and within exercises between conditions. Data showed a significant
      difference on muscle activation based on the interaction between resistance band
      usage and exercise choice (Lambda = 0.276, F24, 136.92 = 3.19, p < 0.001). Adding
      a resistance band was effective in increasing muscle activation within the
      scapular stabilizing musculature. Conversely, the use of a resistance band was
      not as effective in increasing the activation of LPHC musculature. Future studies
      should investigate exercises that increase LPHC musculature activation. Coaches
      and clinicians can use these results to make more informed decisions when
      prescribing exercises to athletes for performance enhancement and rehabilitation.

PMID- 30216254
TI  - More Than a Season.

PMID- 30216255
TI  - The Social Determinants of Trauma: A Trauma Disparities Scoping Review and
      Framework.
AB  - The drivers of trauma disparities are multiple and complex; yet, understanding
      the causes will direct needed interventions. The aims of this article are to (1)
      explore how the injured patient, his or her social environment, and the health
      care system interact to contribute to trauma disparities and examine the evidence
      in support of interventions and (2) develop a conceptual framework that captures
      the socioecological context of trauma disparities. Using a scoping review
      methodology, articles were identified through PubMed and CINAHL between 2000 and
      2015. Data were extracted on the patient population, social determinants of
      health, and interventions targeting trauma disparities and violence. Based on the
      scoping review of 663 relevant articles, we inductively developed a conceptual
      model, The Social Determinants of Trauma: A Trauma Disparities Framework, based
      on the categorization of articles by: institutional power (n = 9), social context
      place (n = 117), discrimination experiences (n = 59), behaviors and comorbidities
      (n = 57), disparities research (n = 18), and trauma outcomes (n = 85).
      Intervention groupings included social services investment (n = 54), patient
      factors (n = 88), hospital factors (n = 27), workforce factors (n = 31), and
      performance improvement (n = 118). This scoping review produced a needed taxonomy
      scheme of the drivers of trauma disparities and known interventions that in turn
      informed the development of The Social Determinants of Trauma: A Trauma
      Disparities Framework. This study adds to the trauma disparities literature by
      establishing social context as a key contributor to disparities in trauma
      outcomes and provides a road map for future trauma disparities research.

PMID- 30216256
TI  - Human Trafficking: Clinical Assessment Guideline.
AB  - Approximately 18,000 people are trafficked into the United States each year and
      forced into commercial sex work. Up to 80% of victims are seen by a health care
      provider. In the health care setting, they rarely identify themselves as victims
      of human trafficking (HT), making it difficult to recognize them. Only a few
      health care professionals know how to identify victims of trafficking among their
      patients. The purpose of this article was to review the process used in health
      care settings to identify victims of traffickers. The author conducted a search
      to locate current scholarly articles addressing HT identification in health care
      settings. Each article was reviewed for its significance in victim
      identification. To address the problem of identifying and assisting patients who
      are being trafficked, some hospitals developed their own protocols. However, the
      wide variation in what is included on these assessment protocols makes it
      difficult to hold up any particular protocol as a national model. The author
      concludes that until more effective standardized national protocols for the
      identification of the HT victim within the health care settings are developed,
      National Human Trafficking Resource Center's method of screening should be used
      to help increase the degree at which patient victims are identified within the
      health care setting.

PMID- 30216257
TI  - Determining the Education and Research Priorities in Pediatric Trauma Nursing: A
      Delphi Study.
AB  - Trauma has a greater impact on morbidity and mortality than all other disease
      processes in the pediatric population; yet, there is a gap in the literature
      related to the scientific basis for educating and researching future practice.
      The purpose of this research study was to utilize the Delphi technique to
      identify the current education and research priorities for pediatric trauma
      nursing as described by the members of the Society of Trauma Nurses. Consensus on
      the education and research priorities was derived from a sample (n = 25) of
      trauma nursing experts. The pediatric trauma nursing education priorities are the
      following: (1) initial resuscitation; (2) assessment; and (3) evidence-based
      practice. The pediatric trauma nursing research priorities are the following: (1)
      impact of nursing care on outcomes; (2) initial resuscitation; and (3) critical
      care. Future efforts in educational program development and research study should
      focus on these priorities.

PMID- 30216258
TI  - Determining the Education and Research Priorities in Pediatric Trauma Nursing: A
      Delphi Study.

PMID- 30216259
TI  - Automated Postdischarge Trauma Patient Call Program.
AB  - Postdischarge phone calls have been shown to improve communications between
      patients and health care providers, potentially reducing readmission rates,
      medication errors, and emergency department (ED) visits. Given the complexity of
      social and medical issues associated with trauma, we studied the utility of an
      automated phone call system as a method of identifying gaps in trauma care. The
      Trauma Program and the Health Management and Education Department at a Level 1
      academic trauma center engaged in a collaborative quality improvement effort
      using the CipherHealth LLC platform to provide automated phone calls to trauma
      patients 2-3 days after discharge. Automated questions to patients focused upon
      symptoms, equipment and medications, discharge instruction comprehension, and
      follow-up needs. When indicated, the automated system sent an alert and prompted
      the timely return phone call to the patient from a registered nurse with the
      intent of addressing the specified issue. During the 4-month study period, 1,382
      patients were discharged from the trauma service. Three hundred thirty-two calls
      were attempted, with 186 completed. Twenty-seven percent of the completed calls
      prompted a nurse to make a personalized callback to the patient. Most calls were
      for symptoms (26%), follow-up appointments (22%), medication issues (21%), and
      discharge instruction clarification (15%). Just over 25% of trauma patients
      requested further clarification after discharge from the hospital. The results of
      this pilot indicate that further follow-up is warranted to determine whether
      outpatient follow-up calls in the trauma population have any impact upon
      mitigating complications and quality measures such as reduced ED visits,
      readmission, and patient safety and satisfaction.

PMID- 30216260
TI  - Clinical Signs of Basilar Skull Fracture and Their Predictive Value in Diagnosis
      of This Injury.
AB  - Although clinical signs for the diagnosis of basilar skull fracture (BSF) are
      ambiguous, they are widely used to make decisions on initial interventions
      involving trauma patients. We aimed to assess the performance of early and late
      (within 48 hr posttrauma) signs for BSF diagnosis and to verify the correlation
      between the presence of these signs and head injury severity. We conducted a
      prospectively designed follow-up study at a referral hospital for trauma care in
      Sao Paulo, Brazil, and performed structured observations for 48 hr post-blunt
      head injury in patients aged 12 years or older. The following signs of BSF were
      considered: raccoon eyes, Battle's sign, otorrhea, and rhinorrhea. Among the 136
      enrolled patients (85.3% male; mean age 40 +/- 21.4 years), 28 patients (20.6%)
      had BSF. The clinical signs for the early or late detection of BSF had low
      accuracy (55.9% vs. 43.4%), specificity (52.8% vs. 30.5%), and positive
      predictive value (25.7% vs. 27.1%). However, the presence of these signs was
      correlated to head injury severity, indicated by the Glasgow Coma Scale (p =
      .041) and Maximum Abbreviated Injury Scale-Head region (p = .002). In view of the
      low accuracy of these signs, resulting low clinical value of their presence, and
      their high sensitivity in the late stage, the study results contraindicate the
      value of BSF signs for making decisions about using the nasal route for the
      introduction of catheters and tubes in initial trauma care.

PMID- 30216261
TI  - The Role of Trauma Video Review in Optimizing Patient Care.
AB  - Trauma video review allows for monitoring of performance improvement initiatives,
      leadership skills, system process issues, and guideline compliance. Despite the
      well-documented benefits, there are persistent barriers to its use including
      patient privacy concerns, cost, and provider anxiety. Optimizing implementation
      by ensuring that informed consent processes are in place, as well as a structured
      peer review process, can help trauma centers overcome these hurdles. Trauma video
      review is a unique and beneficial tool that helps tie patient care to
      quantifiable data, as well as serves as a platform for education opportunities.

PMID- 30216263
TI  - A Tiered Approach to Trauma Education in the Emergency Department.
AB  - Although trauma centers are required to provide trauma education to nurses caring
      for trauma patients, there are no clearly defined standards for this education.
      In an effort to improve emergency department (ED) trauma nursing care, a tiered
      approach to ED trauma education (basic, intermediate, and advanced) was developed
      to provide specialized trauma education to a larger number of ED nurses at a
      Level II trauma center in Georgia. This tiered approach to ED trauma nurse
      education has resulted in the ability to quickly activate multiple trauma teams
      that work together competently and efficiently, leading to improved patient care
      and development of competent ED trauma nurses.

PMID- 30216262
TI  - Evaluating the Effectiveness of the Translated "A Matter of Balance" Fall
      Prevention Program Materials for Non-English-Speaking Participants.
AB  - A Matter of Balance (MOB) is an evidence-based fall prevention program shown to
      reduce fear of falling (FOF) in English-speaking participants. The effectiveness
      of translated (Chinese and Spanish) MOB materials in reducing FOF is unknown. The
      objective of this study was to evaluate whether MOB was associated with reduced
      FOF in Chinese- and Spanish-speaking participants and included an English
      speaking comparison group. Participants were recruited from MOB classes in
      Massachusetts and Illinois. Investigators used the Falls Efficacy Scale
      International (FES-I) and a demographic questionnaire to survey the participants
      at the first class (baseline), the last class, and 6 months after the MOB course.
      Of the 90 participants who enrolled, 77 (85.6%) completed the course (Chinese: n
      = 37; Spanish: n = 19; and English: n = 21) and 54 (60%) completed the 6-month
      survey (Chinese: n = 33; English: n = 21). Chinese FES-I scores significantly
      increased (FOF worsened) at the end of the course (+7.1, p = .009), and 6-month
      survey scores were also significantly above the baseline score (+6.7, p = .0088).
      FES-I scores decreased (FOF declined) in both the Spanish (-6.6, p = .016) and
      English groups (-2.7, p = .14) at the last class, and English 6-month FES-I
      scores were slightly lower than baseline scores (-0.4, p = .8). Participation in
      the MOB program did not reduce FOF in the Chinese population, but MOB did show
      promise in reducing FOF in both the Spanish and English groups. Future studies
      are warranted to explore the cultural, social, and education-related factors that
      may influence effectiveness of the MOB program.

PMID- 30216264
TI  - A Diaphragmatic Hernia and Pericardial Rupture Caused by Blunt Injury of the
      Chest: A Case Review.
AB  - Blunt traumatic diaphragmatic hernias are most commonly seen in combination with
      other injuries. Right diaphragmatic ruptures with serious pericardium ruptures
      are relatively rare. The diagnosis of diaphragmatic hernias is not difficult;
      however, prior to surgery, it is difficult to judge whether pericardium damage
      has occurred, particularly on the right side. This injury may occur in a critical
      pathological state in which cardiac tissue is outside the pericardium due to the
      pericardial defect. Severe hemodynamic disorders or even death may occur if the
      patient's condition is not diagnosed and treated in a timely manner. The
      transportation of patients with severe trauma must be performed with extreme
      caution. It is necessary to weigh a wide range of differential diagnoses in a
      serious and thorough initial investigation.

PMID- 30216265
TI  - Effects of a Safety-Awareness-Promoting Program Targeting Mothers of Children
      Aged 0-6 Years to Prevent Pediatric Injuries in the Home Environment:
      Implications for Nurses.
AB  - Pediatric injuries pose a significant problem, both in Turkey and worldwide,
      because they lead to death or disability in a number of children each year. This
      quasi-experimental study aimed to identify the effects of the training provided
      to mothers with children aged 0-6 years about the hazards that lead to pediatric
      injuries. The population of the research comprised mothers with children aged 0-6
      years, living in the city center. Considering the educational and socioeconomic
      levels of the individuals registered in the family health centers (FHC), the FHCs
      were divided into 3 groups of high, moderate, and low socioeconomic level.
      Subsequently, 1 FHC was selected from each level using simple random sampling.
      The study was conducted with 300 volunteer mothers registered in these FHCs. The
      tools used for data collection included the "0-6-year-old Children's Mothers'
      Identification Scale of Safety Precautions for the Prevention of Pediatric
      Injuries," the "Risk Assessment Form for Pediatric Injuries" (RAF), and a 33-item
      questionnaire. After the training on the prevention of pediatric injuries, the
      mothers' scores on the identification of safety precautions for pediatric
      injuries increased significantly (p = 000). In addition, there was a significant
      difference between the pre- and posttest scores of the mothers (p < .05) on all
      dimensions of the RAF (choking, burns, poisoning, sharp object injuries, and
      falling; all p values <.05). Thus, the training provided to mothers to prevent
      pediatric injuries was effective in improving the awareness of the mothers.

PMID- 30216266
TI  - Magnitude-based Inference: Good Idea but Flawed Approach.

PMID- 30216267
TI  - Isolated "Low" Test Scores Are Often Normal and Valid.

PMID- 30216268
TI  - Response.

PMID- 30216269
TI  - Validation of Step Counters in the Free-living Context.

PMID- 30216270
TI  - Response.

PMID- 30216271
TI  - Effects of Strength Training on Postpubertal Adolescent Distance Runners
      Corrigendum.

PMID- 30216272
TI  - The Influence of Wildland Fire Operations on Adipose Tissue, Skeletal Muscle and
      Lipids-Corrigendum.

PMID- 30216273
TI  - The Influence of Culture on Teamwork and Communication in a Simulation-Based
      Resuscitation Training at a Community Hospital in Honduras.
AB  - STATEMENT: Communication and teamwork are important aspects of medicine and have
      been a recent focus of resuscitation. Culture can influence communication and
      teamwork, and these effects have not been studied in low-resource settings. Using
      a case study and the TEAM scale, we evaluated how culture influences teamwork and
      communication during resuscitation simulations, in addition to examining other
      challenges of simulation research in low-resource settings. We observed lower
      scores in leadership and communication skills than have been seen in other
      studies using the TEAM scale, which led us to evaluate the possible role of
      culture in influencing these skills. The high power distance and collectivism in
      Latin America can make communication difficult, especially during debriefing.
      Furthermore, in a male-biased medical hierarchy, female nurses may be less likely
      to voice concerns. Ultimately, this commentary provides advice for taking the
      influences of culture into account when planning future simulation training in
      low-resource settings.

PMID- 30216274
TI  - Validation of the FAST Workstation as an Objective Evaluator of Hand-Tied
      Surgical Knots.
AB  - INTRODUCTION: Hand-tying surgical knots is an important skill that is applicable
      across all surgical disciplines. Knot quality is traditionally assessed in the
      operating room by visual inspection, which is inherently subjective. With the
      increasing prevalence of simulation training, surgical trainees having access to
      objective feedback of their knot-tying skills are paramount for skill evaluation.
      Our study aimed to validate a mechanical suture loop security tester as an
      objective evaluation method of hand-tied surgical knot quality. METHODS: Seventy
      three subjects were recruited and categorized based on surgical expertise into
      one of the following three groups: medical students, surgical residents, and
      attending surgeons. They hand-tied five surgical knots consecutively using 0
      Vicryl sutures. The knots were tested using the suture loop security workstation
      with 10 lbs of linear force for 10 seconds. Success of the suture loop was set at
      less than 3 mm of loop expansion. This protocol was based on previous research
      showing that 3 mm of loop expansion would represent clinical failure of the knot
      in vivo. RESULTS: The students, residents, and attending surgeons tied a median
      of two, three, and four successful knots, respectively. Post hoc pairwise
      comparisons revealed that residents tied more successful knots than students (p <
      0.001), and attending physicians tied more successful knots than students (p <
      0.001). However, there was no statistically significant difference in the number
      of successes between residents and attending physicians (p = 0.24). CONCLUSIONS:
      Using the mechanical loop security workstation demonstrates construct validity as
      a reliable objective evaluation tool of hand-tied surgical knots.

PMID- 30216275
TI  - In Situ Simulation to Mitigate Threats to Participation in a Multicenter Clinical
      Trial in High-Acuity, Low-Frequency Setting.
AB  - INTRODUCTION: Multicenter clinical trials of high-acuity, low-frequency
      emergencies are expensive and resource intensive. Current standards for trial
      preparation have significant limitations. Our objective is to describe our use of
      in situ simulation (ISS) to identify and mitigate threats to enrollment, protocol
      adherence, and patient safety in preparation for a multicenter clinical trial of
      antiepileptics for status epilepticus in the emergency department. METHODS: This
      is a descriptive study of ISS conducted in the emergency department at a free
      standing, academic pediatric institution. We designed two scenarios, one for an
      eligible and ineligible patient, to allow care teams to complete all study
      procedures. All study training was completed before the first ISS. Participants
      included physicians, nurses, patient care assistants, paramedics, research
      coordinators, and pharmacists. Ten-minute simulations were followed by 10-minute
      debriefings, led by trained facilitators using a standard template. Data on
      threats to enrollment, protocol adherence, and patient safety were recorded.
      Mitigation strategies were developed by the study team and local experts in ISS.
      RESULTS: Ten of 18 planned simulations were conducted. Seven of 10 completed
      simulations were study eligible patients, with 73 total participants. Nine
      threats to enrollment and five to protocol adherence were identified. Five of 14
      were also threats to patient safety. Mitigation strategies included creation of
      decision aid tools, targeted education during debriefings, adapting study
      material for use, and revision of status epilepticus treatment algorithm.
      CONCLUSIONS: The addition of ISS to standard preparation for a multicenter
      clinical trial facilitated the identification and mitigation of threats to study
      participation and patient safety.

PMID- 30216276
TI  - Simulation Faculty Development: Continuing the Dialogue.

PMID- 30216278
TI  - Society Guidelines Infographic: SASM Guideline on Intraoperative Management of
      OSA.

PMID- 30216277
TI  - Learners' Experiences During Rapid Cycle Deliberate Practice Simulations: A
      Qualitative Analysis.
AB  - INTRODUCTION: Rapid Cycle Deliberate Practice (RCDP) is a team-based simulation
      method, emphasizing repetitive practice over reflective debriefing, with
      progressively more challenging rounds, frequent starts and stops, and direct
      coaching. Although some studies have shown improved performance, no study has
      evaluated learners' perceptions. We aimed to explore learners' experiences during
      RCDP. METHODS: This was a qualitative study of participants' perceptions
      regarding RCDP during their pediatric emergency medicine rotation. Participants
      completed surveys about RCDP learning. A purposive sample of residents and nurses
      were interviewed. Two coders analyzed all interview transcripts to identify
      emerging themes. Constant comparison analysis was performed until thematic
      saturation was achieved. RESULTS: Forty-four participants completed surveys.
      Participants found RCDP interruptions beneficial and felt that they learned most
      during interruptions. Participants who were able to compare traditional and RCDP
      simulations felt that RCDP allowed more focused correction of mistakes,
      acquisition of new skills, and timely practice of team behaviors. Fourteen
      participants were interviewed. Three themes emerged. (1) The real-time
      corrections during RCDP allowed for learning and creation of new skills through
      repetition and practice. (2) The RCDP allowed learners to gain confidence,
      decrease anxiety, and learn in a safe environment. (3) By introducing new
      information in smaller chunks, participants maximized learning without cognitive
      overload. CONCLUSIONS: Rapid Cycle Deliberate Practice is well received by
      learners. Because of frequent interruptions, learners noted early error
      correction, a safe learning environment, and skill improvement during RCDP.
      Learners recognized that the progressive advancement of RCDP helped prevent
      cognitive overload. Future studies should measure cognitive load and skills
      retention.

PMID- 30216279
TI  - Poor Sleep, Worse Outcomes: Obstructive Sleep Apnea and Perioperative Care.

PMID- 30216280
TI  - Maternal Hemorrhage-Regional Versus General Anesthesia: Does It Really Matter?

PMID- 30216282
TI  - Natural Born Survivors?

PMID- 30216281
TI  - Optimal Organization of Acute Pain Services: At the Confluence of Semantics,
      Logistics, and Economics.

PMID- 30216283
TI  - Target-Controlled Infusion: Not a One-Sized-Fits-All Answer to Drug
      Administration.

PMID- 30216284
TI  - Subspecialization ... and Clinical Guidelines.

PMID- 30216286
TI  - Identifying the Best Cut-Point for a Biomarker, or Not.

PMID- 30216285
TI  - An Intellectual Framework for Drug Administration Methods in Anesthesia: Three
      Practice Domains.

PMID- 30216287
TI  - To Thine Own Self Be True: A First Step Toward Learning How Anesthesiologists
      Deal With Adversity in the Operating Room.

PMID- 30216288
TI  - Surveying the Literature: Synopsis of Recent Key Publications.

PMID- 30216289
TI  - Sevoflurane Protects Hepatocytes From Ischemic Injury by Reducing Reactive Oxygen
      Species Signaling of Hepatic Stellate Cells: Translational Findings Based on a
      Clinical Trial.
AB  - BACKGROUND: Randomized controlled trials (RCTs) data demonstrate that sevoflurane
      postconditioning improves clinical outcomes of liver resection with inflow
      occlusion, presumably due to hepatocyte protection from ischemic injury. However,
      mechanisms remain unclear. This study examines liver biopsy samples obtained in
      an RCT of sevoflurane postconditioning to test the hypothesis that sevoflurane
      attenuates hepatocyte apoptosis. METHODS: Messenger ribonucleic acid (mRNA) of
      pro- and antiapoptotic regulators Bax and B-cell lymphoma 2 (Bcl2) was examined
      in hepatic biopsies obtained during the RCT. Hepatic stellate cells (HSCs) and
      hepatocytes were exposed to hypoxia/reoxygenation (H/R) in vitro to evaluate the
      effect of sevoflurane postconditioning on apoptosis. The role of HSC as a
      potential apoptosis trigger in hepatocytes through the production of reactive
      oxygen species induced by H/R was explored by transferring supernatants from H/R
      exposed HSC to hepatocytes as target cells. RESULTS: In patients of the RCT, the
      Bax/Bcl2 mRNA ratio in liver tissue was markedly decreased in the sevoflurane arm
      (25% +/- 21% reduction; P = .001). In vitro, H/R increased reactive oxygen
      species production in HSC by 33% +/- 16% (P = .025), while it was abolished in
      the presence of sevoflurane (P < .001). In hepatocytes, caspase was minimally
      activated by H/R. However, incubation of hepatocytes with supernatants of HSC,
      previously exposed to H/R, increased caspase activity by 28% +/- 13% (P < .001).
      When exposed to supernatants from HSC undergoing sevoflurane postconditioning,
      caspase activation in hepatocytes was reduced by 20% +/- 9% (P < .001), similarly
      to the sevoflurane effect on the BAX/Bcl2 mRNA ratio in the liver samples.
      CONCLUSIONS: The study shows that sevoflurane postconditioning affects apoptosis
      of hepatocytes after ischemia-reperfusion injury in patients. It also
      demonstrates that HSC may be the effector cells of sevoflurane protection.

PMID- 30216290
TI  - Priscilla M. Clarkson Undergraduate Travel Award.

PMID- 30216291
TI  - Peripheral Fatigue: Has Another "Threshold" Bitten the Dust?

PMID- 30216292
TI  - "Live High-Train Low" Paradigm: Moving the Debate Forward.

PMID- 30216293
TI  - Response.

PMID- 30216295
TI  - Early Declines in Vaccine Type Pneumococcal Carriage in Children Less Than 5
      Years Old After Introduction of 10-valent Pneumococcal Conjugate Vaccine in
      Mozambique.
AB  - BACKGROUND: Pneumococcal carriage is a precursor of invasive pneumococcal
      disease. Mozambique introduced 10-valent pneumococcal conjugate vaccine (PCV10)
      in April 2013, using a 3-dose schedule without a booster. We evaluated PCV10
      impact on pneumococcal carriage and colonization density by HIV status. METHODS:
      We conducted 2 cross-sectional surveys (pre and post PCV10 introduction) among
      children 6 weeks to 59 months old. Participants included HIV-infected children
      presenting for routine care at outpatient clinics and a random sample of HIV
      uninfected children from the community. We collected demographic data,
      vaccination history and nasopharyngeal swabs. Swabs were cultured and isolates
      serotyped by Quellung. We selected serotypes 11A, 19A and 19F for bacterial
      density analyses. We compared vaccine-type (VT) carriage prevalence from the pre
      PCV10 with the post-PCV10 period by HIV status. FINDINGS: Prevalence of VT
      carriage declined from 35.9% (110/306) pre already defined in the background. It
      should be pre-PCV (PCV) to 20.7% (36/174 fully vaccinated) post PCV (P < 0.001)
      in HIV-uninfected and from 34.8% (144/414) to 19.7% (27/137 fully vaccinated) (P
      = 0.002) in HIV-infected children. Colonization prevalence for the 3 serotypes
      (3, 6A, 19A) included in the 13-valent PCV but not in PCV10 increased from 12.4%
      (38/306) to 20.7% (36/174 fully vaccinated) (P = 0.009) among HIV- uninfected
      children, mainly driven by 19A; no significant increase was observed in HIV
      infected children. VT carriage among unvaccinated children decreased by 30% (P =
      0.005) in HIV-infected children, with no significant declines observed in HIV
      uninfected children. CONCLUSION: Declines in VT carriage were observed in both
      HIV-uninfected and HIV-infected children after PCV10 introduction with an early
      signal of herd effect especially in HIV-infected children. Ongoing monitoring of
      increases in 19A carriage and disease is necessary.

PMID- 30216297
TI  - What's New in Shock, October 2018?

PMID- 30216296
TI  - Treatment of Multidrug-Resistant Tuberculosis Infection in Children.

PMID- 30216294
TI  - Congenital Cytomegalovirus and HIV Perinatal Transmission.
AB  - BACKGROUND: Congenital cytomegalovirus (CMV) infection (cCMV) is an important
      cause of hearing loss and cognitive impairment. Prior studies suggest that HIV
      exposed children are at higher risk of acquiring cCMV. We assessed the presence,
      magnitude and risk factors associated with cCMV among infants born to HIV
      infected women, who were not receiving antiretrovirals during pregnancy. METHODS:
      cCMV and urinary CMV load were determined in a cohort of infants born to HIV
      infected women not receiving antiretrovirals during pregnancy. Neonatal urines
      obtained at birth were tested for CMV DNA by qualitative and reflex quantitative
      real-time polymerase chain reaction. RESULTS: Urine specimens were available for
      992 (58.9%) of 1684 infants; 64 (6.5%) were CMV-positive. Mean CMV load (VL) was
      470,276 copies/ml (range: < 200-2,000,000 copies/ml). Among 89 HIV-infected
      infants, 16 (18%) had cCMV versus 42 (4.9%) of 858 HIV-exposed, uninfected
      infants (P < 0.0001). cCMV was present in 23.2% of infants with in utero and 9.1%
      infants with intrapartum HIV infection (P < 0.0001). Rates of cCMV among HIV
      infected infants were 4-fold greater (adjusted OR, 4.4; 95% CI: 2.3-8.2) and 6
      fold greater among HIV in utero-infected infants (adjusted OR, 6; 95% CI: 3-12.1)
      compared with HIV-exposed, uninfected infants. cCMV was not associated with mode
      of delivery, gestational age, Apgar scores, 6-month infant mortality, maternal
      age, race/ethnicity, HIV viral load or CD4 count. Primary cCMV risk factors
      included infant HIV-infection, particularly in utero infection. CONCLUSION: High
      rates of cCMV with high urinary CMV VL were observed in HIV-exposed infants. In
      utero HIV infection appears to be a major risk factor for cCMV in infants whose
      mothers have not received combination antiretroviral therapy in pregnancy.

PMID- 30216298
TI  - Toll-Like Receptor 4 and NLRP3 Caspase 1- Interleukin-1beta-Axis are Not Involved
      in Colon Ascendens Stent Peritonitis-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 toll-like receptor 4 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 colon
      ascendens stent peritonitis (CASP) model. The QJ interval was increased in wild
      type C57BL/6J mice after CASP when compared with sham controls, a result
      paralleled by an increase in the cardiac action potential (AP) duration (APD).
      The decreases in ejection fraction (EF), left ventricle end diastolic volume,
      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 cecal ligation and puncture. Despite developing cardiac dysfunction similar
      to wild types after CASP, Nlrp3 mice had reduced circulating levels of
      interleukin (IL)-1beta, IL-6 and tumor necrosis factor-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- 30216299
TI  - Hypoactive Delirium Is More Appropriately Named as "Acute Apathy Syndrome".

PMID- 30216300
TI  - It Was the Best of Rounds, It Was the Worst of Rounds, It Was the Age of Wisdom,
      It Was the Age of Electronic Health Records....

PMID- 30216301
TI  - A Single Certification Exam in Critical Care?: "It Ain't Over Til It's Over".

PMID- 30216302
TI  - SEP-1: The Lactate Myth and Other Fairytales.

PMID- 30216303
TI  - The Changing Paradigm of Sepsis: Early Diagnosis, Early Antibiotics, Early
      Pressors, and Early Adjuvant Treatment.

PMID- 30216304
TI  - Fluid, Fluid Everywhere, and All the Organs Did Not Shrink; Fluid, Fluid
      Everywhere, Administered Without a Think.

PMID- 30216305
TI  - Conditional Hemodynamic Tolerance to Decremental Recruitment of the "Open Lung".

PMID- 30216306
TI  - Are We Really Doing More With Less: The Value of Half-Dose Alteplase in Pulmonary
      Embolism Therapy.

PMID- 30216307
TI  - Too Much Pressure at the Bedside...

PMID- 30216308
TI  - What Is the Best Treatment for Vancomycin-Resistant Enterococcal Bloodstream
      Infections?

PMID- 30216309
TI  - Ventilator-Associated Pneumonia: Are the Antibiotics the Solution?

PMID- 30216310
TI  - Impaired Cerebral Metabolism in Injured Brain: Can Lactate Step in for Glucose?

PMID- 30216311
TI  - Probiotics in Pediatric Severe Sepsis: The Time Has Come to Trust Our 'Gut'!

PMID- 30216312
TI  - For Better Neuropsychiatric Outcomes, Minimize Benzodiazepines.

PMID- 30216313
TI  - Acute Respiratory Failure in Pediatric Patients After Hematopoietic Stem Cell
      Transplantation-Understanding More by Working Together.

PMID- 30216314
TI  - Neuromuscular Blockade in Targeted Temperature Management: Giving More or Giving
      Less?

PMID- 30216315
TI  - Early Administration of Ramelteon in the ICU: Effects Deserve Further Study.

PMID- 30216316
TI  - The authors reply.

PMID- 30216317
TI  - Early Identification of Acute Respiratory Distress Disorder in the Absence of
      Positive Pressure Ventilation: A Need for a Dedicated Randomized Control Trial to
      Determine Attainability.

PMID- 30216318
TI  - The authors reply.

PMID- 30216319
TI  - Temporary Mechanical Support in Septic Cardiomyopathy.

PMID- 30216320
TI  - The authors reply.

PMID- 30216321
TI  - Long-Term Cognitive Outcomes After Extracorporeal Membrane Oxygenation.

PMID- 30216322
TI  - The authors reply.

PMID- 30216323
TI  - Extracorporeal Treatment for Paraquat Poisoning.

PMID- 30216324
TI  - The authors reply.

PMID- 30216325
TI  - Out With the Old, in With the New: The Improved Prognosis of Critically Ill
      Patients With Cirrhosis.

PMID- 30216326
TI  - The authors reply.

PMID- 30216327
TI  - Noninvasive Ventilation Versus High-Flow Nasal Oxygen for Acute Respiratory
      Distress Syndrome: Where Next?

PMID- 30216328
TI  - The authors reply.

PMID- 30216329
TI  - Boarding Rather Than Boring, How Do We Best Juggle Our ICU Outliers?

PMID- 30216330
TI  - The authors reply.

PMID- 30216331
TI  - Challenges to Interprofessional Care in the ICU Environment.

PMID- 30216332
TI  - Calciphylaxis: Case Presentation and Review of the Literature.
AB  - BACKGROUND: Calciphylaxis is a potentially life-threatening condition involving
      painful necrotic skin ulcerations, especially of the lower extremities. It is
      generally associated with chronic kidney failure but may be seen in nonuremic
      cases. CASE REPORT: We report a case of calciphylaxis in a 60-year-old man with
      diabetes on dialysis for end-stage renal disease and known to have other typical
      combination of risk factors associated with calciphylaxis syndrome. On
      examination, he presented with multiple intensely painful calciphylaxis wounds on
      his legs and ankles. Despite regular wound management of his condition in our
      ambulatory care setting, his ulcers deteriorated. The patient's pain also
      increased and he was referred for hospital admission. CONCLUSION: This case
      presentation emphasizes the importance of an interdisciplinary team in the
      treatment of the complex, life-threatening cutaneous manifestations of
      calciphylaxis. When indicated, prompt referral to a hospital setting is necessary
      for appropriate care.

PMID- 30216333
TI  - The Evolving Story of Pterygium.
AB  - Pterygium is a fibrovascular subepithelial growth of degenerative tissue over the
      limbus. It is a common condition worldwide that is especially prevalent in
      tropical countries within the "pterygium belt." Its exact etiology remains to be
      elucidated; however, it is strongly associated with exposure to ultraviolet
      light. The high expression levels of tumor protein p53 (TP53) observed in
      laboratory studies of pterygium seem to contradict the fast-growing nature of its
      clinical behavior, and TP53 mutations have been suggested. We demonstrated that
      mouse double minute 2 (MDM2), a TP53-binding protein, contributes to the
      inhibition of TP53 activity in human pterygium. Thus, disruption of the MDM2-TP53
      interaction should attenuate human pterygium cell growth. For primary pterygium,
      treatment is relatively straightforward and involves surgical excision. To
      minimize the risk of recurrence, many adjunctive therapies are adopted, including
      antimetabolites, such as mitomycin C and 5-fluorouracil, amniotic membrane,
      different variations on conjunctival and/or limbal conjunctival grafts, and other
      medications such as anti-vascular endothelial growth factor. In the future, MDM2
      antagonists may help further lower the recurrence rates after the treatment of
      pterygium.

PMID- 30216334
TI  - Combined Keratoplasty, Pars Plana Vitrectomy, and Flanged Intrascleral
      Intraocular Lens Fixation to Restore Vision in Complex Eyes With Coexisting
      Anterior and Posterior Segment Problems.
AB  - PURPOSE: To restore vision in complex eyes with coexisting anterior and posterior
      segment problems, combined corneal transplantation (penetrating keratoplasty [PK]
      or Descemet-stripping automated endothelial keratoplasty [DSAEK]), pars plana
      vitrectomy (PPV), and/or flanged intrascleral intraocular lens (IOL) fixation,
      designated vitreocorneal surgery are performed. In this study, we evaluated the
      usefulness of vitreocorneal surgery for eyes with complex comorbidities. METHODS:
      Thirteen consecutive eyes in 13 patients with coexisting corneal pathology (ie,
      corneal scarring, bullous keratoplasty, corneal laceration) and posterior segment
      pathology (ie, aphakia without capsular support, retinal detachment, intravitreal
      foreign body) underwent vitreocorneal surgery. Visual outcomes, intraoperative
      and postoperative complications, and additional surgery were retrospectively
      evaluated. RESULTS: Vitreocorneal surgery included PK + PPV + intrascleral IOL
      fixation (n = 5), PK + PPV (n = 3), PK + intrascleral IOL fixation (n = 1), DSAEK
      + intrascleral IOL fixation (n = 1), and DSAEK + PPV + intrascleral IOL fixation
      (n = 3). An intraoperative Eckardt temporary keratoprosthesis use enabled safe
      PPV. No vitreoretinal/IOL complications occurred. One eye required repeat DSAEK
      to repair endothelial graft detachment and inversion. In 3 eyes, secondary
      glaucoma was subsequently treated by glaucoma drainage device implantation
      through the pars plana. Mean best spectacle-corrected visual acuity (logMAR)
      improved from 1.8 +/- 0.9 preoperatively to 1.1 +/- 0.6 at 11.2 +/- 14.6 months
      postoperatively (P = 0.002). Postoperative refraction was -0.68 +/- 2.56 D
      (spherical equivalent). CONCLUSIONS: PK or DSAEK with PPV and/or flanged
      intrascleral IOL fixation is useful for complex eyes with coexisting anterior and
      posterior segment problems.

PMID- 30216335
TI  - Time-Course Investigation of Intervertebral Disc Degeneration Induced by
      Different Sizes of Needle Punctures in Rat Tail Disc.
AB  - BACKGROUND This study aimed to determine the best size needle to use in inducing
      IVDD and to find the proper time point of disc degeneration suitable for further
      biologic treatment study. MATERIAL AND METHODS First, rat tail level 5/6, 7/8,
      and 9/10 discs were punctured by 18G, 21G, or 25G needles. Then, degeneration was
      assessed by radiography, MRI, and histological evaluation at 2, 4, and 6 weeks
      after puncture. Later, real-time reverse transcriptase (RT-PCR) was used to
      examine mRNA expressions of aggrecan, collagen type II, hypoxia-inducible factor
      1a (HIF-1a), glucose transporter1 (GLUT-1), and vascular endothelial growth
      factor (VEGF). RESULTS Significant differences were identified in almost all
      parameters compared with the control group in the 18G and 21G group at almost all
      time points. To assess the effect of different needle sizes on DHI, we used
      magnetic resonance imaging (MRI), grade, and mRNA expression. We found
      significant differences between different groups, except for DHI between the 21G
      group and 25G group and MRI grade between the 18G and 21G group at the 2-week
      time point. In assessing the effect of different needle sizes on HE staining
      score and toluidine blue staining grade, statistical differences were observed at
      some time points. The effects of time on all parameters were significant at
      almost all time points in all groups. CONCLUSIONS The middle-size needle (21G)
      performed better in inducing disc degeneration. The 2-week time point may be
      better for use in further experimental studies.

PMID- 30216336
TI  - An index to quantify individual social responsibility in the decision to be
      vaccinated.
AB  - In the context of generic infectious disease studies, the aim of this paper is to
      quantify and represent the individual social responsibility based on whether or
      not a single individual is vaccinated. Although the objective of this study is
      merely educational the approach implemented is based on a classical mathematical
      model named S.I.R. (Susceptible-Infected-Recovered) using an impulsive
      vaccination strategy. Dates of vaccination and fraction of individuals vaccinated
      are used as parameters. In addition, numerical simulations are conducted to
      represent the outcomes regarding the reduction of infected cases through tables
      and graphs.

PMID- 30216337
TI  - n-Butyl-2-cyanoacrylate tissue adhesive (Histoacryl) vs. subcuticular sutures for
      skin closure of Pfannenstiel incisions following cesarean delivery.
AB  - BACKGROUND: Tissue adhesives are now routinely used for skin closure in various
      surgeries. This study aimed to evaluate the safety and efficacy of n-butyl-2
      cyanoacrylate (NBCA) tissue adhesive in cesarean delivery by comparing it with
      the safety and efficacy of subcuticular suture closure. METHODS AND FINDINGS: A
      retrospective chart review was undertaken of all patients who underwent cesarean
      delivery via Pfannenstiel skin incision. During the study period, a total of 209
      patients had NBCA (Histoacryl(r)) closure and 208 patients had suture closure.
      Wound complications and Vancouver scar scale (VSS) scores were compared between
      the 2 groups. RESULTS: There were no significant differences between the two
      groups in indications for cesarean deliveries or number of previous cesarean
      deliveries. Incidences of wound disruption and infection were also similar
      between the two closure groups (p = 0.322 and 0.997, respectively). The rate of
      wound complications was 3.4% in the NBCA group and 5.3% in the suture group. All
      complications healed uneventfully with topical antibiotics or closure strips. VSS
      scores at 6-8 weeks after operation were not significantly different between the
      two groups (p = 0.858). These results were corroborated by propensity score
      matching analysis. CONCLUSIONS: NBCA may be a useful skin closure of Pfannenstiel
      skin incisions after cesarean delivery.

PMID- 30216338
TI  - Effect of NaCl-stressed Bacillus thuringiensis (Bt) cotton on the feeding
      behaviors and nutritional parameters of Helicoverpa armigera.
AB  - Saline-alkali soil is an arable land resource on which transgenic Bacillus
      thuringiensis (Bt) cotton has been planted on a large scale in accordance with
      food security strategies. There are, however, concerns about the insecticidal
      effects of Bt cotton on target insect pests. In this study, a Bt cotton variety,
      GK19, and its nontransgenic parent variety, Simian-3, were used as experimental
      models for investigating the effect of the expression of exogenous insecticidal
      proteins in Bt cotton under NaCl stress on the feeding behavior and nutritional
      parameters of Helicoverpa armigera. The results showed that the expression of
      exogenous insecticidal proteins in GK19 was significantly inhibited under NaCl
      stress. However, the feeding, crawling, resting and spinning down behavior of the
      5th instar H. armigera larvae on GK19 Bt cotton, as well as the amount of food
      consumed and feces produced by these larvae, did not markedly differ under
      different NaCl concentrations. In contrast, the mean relative growth rate (MRGR),
      relative growth rate (RGR), approximate digestibility (AD), efficiency of
      conversion of ingested food (ECI) and efficiency of conversion of digested food
      (ECD) of the larvae markedly decreased in response to NaCl stress. Under the same
      concentration of NaCl, the nutritional parameters of the bollworm larvae on GK19
      Bt cotton or Simian-3 nontransgenic cotton were different. However, the
      interaction between salt stress and cotton variety had no significant effect on
      the feeding behavior or nutritional parameters of H. armigera larvae. These
      results may provide a scientific basis for determining the effect of exogenous
      insecticidal protein expression in Bt cotton under NaCl stress on H. armigera and
      can therefore be useful for the effective application of Bt cotton in saline
      alkali soils to prevent and control H. armigera.

PMID- 30216340
TI  - Learned predictiveness acquired through experience prevails over the influence of
      conflicting verbal instructions in rapid selective attention.
AB  - Previous studies have provided evidence that selective attention tends to
      prioritize the processing of stimuli that are good predictors of upcoming events
      over nonpredictive stimuli. Moreover, studies using eye-tracking to measure
      attention demonstrate that this attentional bias towards predictive stimuli is at
      least partially under voluntary control and can be flexibly adapted via
      instruction. Our experiment took a similar approach to these prior studies,
      manipulating participants' experience of the predictiveness of different stimuli
      over the course of trial-by-trial training; we then provided explicit verbal
      instructions regarding stimulus predictiveness that were designed to be either
      consistent or inconsistent with the previously established learned
      predictiveness. Critically, we measured the effects of training and instruction
      on attention to stimuli using a dot probe task, which allowed us to assess rapid
      shifts of attention (unlike the eye-gaze measures used in previous studies).
      Results revealed a rapid attentional bias towards stimuli experienced as
      predictive (versus those experienced as nonpredictive), that was completely
      unaffected by verbal instructions. This was not due to participants' failure to
      recall or use instructions appropriately, as revealed by analyses of their
      learning about stimuli, and their memory for instructions. Overall, these
      findings suggest that rapid attentional biases such as those measured by the dot
      probe task are more strongly influenced by our prior experience during training
      than by our current explicit knowledge acquired via instruction.

PMID- 30216339
TI  - Activating PAX gene family paralogs to complement PAX5 leukemia driver mutations.
AB  - PAX5, one of nine members of the mammalian paired box (PAX) family of
      transcription factors, plays an important role in B cell development.
      Approximately one-third of individuals with pre-B acute lymphoblastic leukemia
      (ALL) acquire heterozygous inactivating mutations of PAX5 in malignant cells, and
      heterozygous germline loss-of-function PAX5 mutations cause autosomal dominant
      predisposition to ALL. At least in mice, Pax5 is required for pre-B cell
      maturation, and leukemic remission occurs when Pax5 expression is restored in a
      Pax5-deficient mouse model of ALL. Together, these observations indicate that
      PAX5 deficiency reversibly drives leukemogenesis. PAX5 and its two most closely
      related paralogs, PAX2 and PAX8, which are not mutated in ALL, exhibit
      overlapping expression and function redundantly during embryonic development.
      However, PAX5 alone is expressed in lymphocytes, while PAX2 and PAX8 are
      predominantly specific to kidney and thyroid, respectively. We show that forced
      expression of PAX2 or PAX8 complements PAX5 loss-of-function mutation in ALL
      cells as determined by modulation of PAX5 target genes, restoration of
      immunophenotypic and morphological differentiation, and, ultimately, reduction of
      replicative potential. Activation of PAX5 paralogs, PAX2 or PAX8, ordinarily
      silenced in lymphocytes, may therefore represent a novel approach for treating
      PAX5-deficient ALL. In pursuit of this strategy, we took advantage of the fact
      that, in kidney, PAX2 is upregulated by extracellular hyperosmolarity. We found
      that hyperosmolarity, at potentially clinically achievable levels,
      transcriptionally activates endogenous PAX2 in ALL cells via a mechanism
      dependent on NFAT5, a transcription factor coordinating response to
      hyperosmolarity. We also found that hyperosmolarity upregulates residual wild
      type PAX5 expression in ALL cells and modulates gene expression, including in
      PAX5-mutant primary ALL cells. These findings specifically demonstrate that
      osmosensing pathways may represent a new therapeutic target for ALL and more
      broadly point toward the possibility of using gene paralogs to rescue mutations
      driving cancer and other diseases.

PMID- 30216342
TI  - A new use of technology to solve an old problem: Estimating the population size
      of a burrow nesting seabird.
AB  - Estimating the population of burrow-nesting seabirds is a challenging task, as
      human presence in the colony creates disturbances and can damage burrows and
      occupants. Here, we present a novel method using aerial photographs taken with
      Unmanned Aerial Vehicles (UAVs) to estimate the population size of a burrow
      nesting seabird, the Black-vented Shearwater (Puffinus opisthomelas), on
      Natividad Island, Mexico. Our results provide a census of burrows in the colony,
      with very low detection error (5.6%). This is greater accuracy compared to other
      methods based on extrapolating results from sample plots to total colony area. We
      then combined this burrow census with ground truth data on occupancy to estimate
      population size. We obtained a population estimate of 37,858 and 46,322 breeding
      pairs for 2016 and 2017 respectively. The proposed method provides a cost
      effective and repeatable approach for monitoring numbers of burrows occupied in a
      colony, thereby enabling easier and faster estimates of population trends. We
      suggest this method can be valid for other burrow-nesting species in habitats
      without dense vegetation cover.

PMID- 30216343
TI  - Trends of admission and predictors of neonatal mortality: A hospital based
      retrospective cohort study in Somali region of Ethiopia.
AB  - BACKGROUND: In Ethiopia, the trend of neonatal mortality showed slow pace of
      reduction from 2000-2016 compared to the reduction in infant and under-five
      mortality over the same period. This study aimed at unpacking the trends of
      admission, specific causes and rate of neonatal mortality as well as predictors
      of neonatal mortality at a general hospital in Somali region of Ethiopia.
      METHODS: A hospital based retrospective cohort study was conducted from 25th of
      May 2017to 10th of June, 2017. All the new-borns admitted in the neonatal
      Intensive Care Unit of the hospital were reviewed over three years period
      (Aug2014-May2017). Data were cleaned and exported to SPSS version 20 and both
      descriptive and analytical analysis were executed. The level of significance was
      set at P<0.05. Binary logistic regression was used to produce summary of
      statistics including crude and adjusted odds ratio and 95% confidence intervals.
      RESULTS: This study reviewed a total of 792 new-borns below the age of 28 days
      admitted in the NICU of Karamara hospital over a period of three years (August,
      2014 to May, 2017). The mean birth weight was 2733 +/- 740 g and neonates with
      normal birth weight stood at 64%. Seven hundred forty seven new-borns (94.3%)
      were discharged alive while 45 (5.7%) new-borns died in the course of
      hospitalization making a Neonatal Mortality Rate (NMR) of 5.7% (57 per 1000 live
      births), and 96 percent of these deaths were early neonatal deaths that occurred
      in the first one week of life (i.e. <7 days).After all variables which had an
      association with neonatal mortality (P <0.05) were entered in to a multivariate
      logistic model to control the effect of confounders: prematurity (AOR =
      0.492(0.253, 0.957), P = 0.037) and average length of stay below two days (AOR =
      0.418(0.186, 0.936), P = 0.034) were independently associated with neonatal
      mortality showing protective effect. CONCLUSION: The causes of neonatal death
      reported in this study are preventable, the neonatal mortality rate is high
      compared to the national and regional figures. Prematurity and shorter length of
      stay in the NICU of less than two days showed independent association with
      neonatal mortality. This calls for more work along the continuum of care,
      improving the quality of care, early transfer of sick neonates to the NICU along
      with scaling up establishment of the NICUs in other hospitals of the region.

PMID- 30216341
TI  - Patient-specific pulse wave propagation model identifies cardiovascular risk
      characteristics in hemodialysis patients.
AB  - Risk of cardiovascular associated death in dialysis patients is the highest among
      all other co-morbidities. Improving the identification of patients with the
      highest cardiovascular risk to design an adequate treatment is, therefore, of
      utmost importance. There are several non-invasive cardiovascular state biomarkers
      based on the pulse (pressure) wave propagation properties, but their major
      determinants are not fully understood. In the current study we aimed to provide a
      framework to precisely dissect the information available in non-invasively
      recorded pulse wave in hemodialysis patients. Radial pressure wave profiles were
      recorded before, during and after two independent hemodialysis sessions in 35
      anuric prevalent hemodialysis patients and once in a group of 32 healthy
      volunteers. Each recording was used to estimate six subject-specific parameters
      of pulse wave propagation model. Pressure profiles were also analyzed using
      SphygmoCor software (AtCor Medical, Australia) to derive values of already
      established biomarkers, i.e. augmentation index and sub-endocardial viability
      ratio (SEVR). Data preprocessing using propensity score matching allowed to
      compare hemodialysis and healthy groups. Augmentation index remained on average
      stable at 142 +/- 28% during dialysis and had similar values in both considered
      groups. SEVR, whose pre-dialytic value was on average lower by 12% compared to
      healthy participants, was improved by hemodialysis, with post-dialytic values
      indistinguishable from those in healthy population (p-value > 0.2). The model,
      however, identified that the patients on hemodialysis had significantly increased
      stiffness of both large and small arteries compared to healthy counterparts (>
      60% before dialysis with p-value < 0.05 or borderline) and that it was only
      transiently decreased during hemodialysis session. Additionally, correlation
      based clustering revealed that augmentation index reflects the shape of heart
      ejection profile and SEVR is associated with stiffness of larger arteries.
      Patient-specific pulse wave propagation modeling coupled with radial pressure
      profile recording correctly identified increased arterial stiffness in
      hemodialysis patients, while regular pulse wave analysis based biomarkers failed
      to show significant differences. Further model testing in larger populations and
      investigating other biomarkers are needed to confirm these findings.

PMID- 30216344
TI  - 'Yellow is good for you': Consumer perception and acceptability of fortified and
      biofortified cassava products.
AB  - Vitamin A, an essential micronutrient for health, can be obtained from various
      food sources including cassava products made from either traditional white
      cassava varieties fortified with red palm oil containing provitamin A, or new
      high provitamin A biofortified yellow cassava varieties. Both products have a
      similar yellow appearance due to the coloured pigmentation of provitamin A. Using
      a range of methods to provide a comprehensive understanding of sensory
      acceptability (blind triangle test, sensory profiling, hedonic preference that
      included Check-all-that-applies and Just-about-right tests), we tested the
      acceptability and nutritional perception of traditional West-African food dough
      like products (eba and fufu) made from biofortified, fortified, or control
      products made with non-fortified white cassava (n = 7) at three suburban
      locations near Ibadan, Nigeria on a total of 122 consumers. Biofortified,
      fortified, and control products could be differentiated blindly confirming that
      products clearly differed with respect to other sensory characteristics than
      appearance. Overall biofortified products were better accepted than control and
      fortified ones. Three classes of consumer preference were identified based on the
      dislike for control and fortified products, which indicated that acceptance of
      biofortified products was not a hindrance. On the contrary the traditional
      fortified product had poorer acceptance and this was due to its less desirable
      sensory characteristics as demonstrated by Just-about-right Penalty analysis. A
      majority of consumers (85%) had previous knowledge of biofortified cassava.
      Consumers associated 'yellow colour' with 'good for eyesight', 'good for
      children's health' and 'new'. More nutritional benefits were attributed to
      biofortified than fortified products although they had similar provitamin A
      contents and this demonstrates a bias. We suggest that nutrition promotion
      campaigns to improve the vitamin A status should also encompass all natural
      sources of provitamin A, including biofortified and traditional fortified
      products.

PMID- 30216345
TI  - Click emission in Dall's porpoise Phocoenoides dalli, focusing on physical
      properties of tissues.
AB  - Dall's porpoise (Phocoenoides dalli) is one of most common North Pacific porpoise
      species, for which information on sound-emitting processes is limited. To
      evaluate the mechanism of click emission in the head of this porpoise, the
      distribution of acoustic impedance in head tissues was calculated using density
      and Young's modulus'which is a measure of linear resistance to linear
      compression. Two Dall's porpoise heads were examined: one for macroscopic
      dissection, and one for investigating the distribution of acoustic impedance
      calculated from CT-measured density, and Young's modulus measured by creep meter.
      Acoustic impedance increased from the dorsal bursae to the melon's emitting
      surface, with impedance matching observed at the boundary between the emitting
      surface and seawater, and was more similar in distribution to Young's modulus
      than it was to density. The distribution of acoustic impedance differed from that
      of harbor porpoise (Phocoena phocoena), despite similarities in the sound
      producing organs in the heads of Dall's and harbor porpoises. A comparison of the
      physical properties of Dall's and harbor porpoise head tissues suggests that
      hypertrophic vestibular sacs and an oval emitting surface are common
      characteristics in Phocoenidae.

PMID- 30216347
TI  - Matching geographical assignment by stable isotopes with African non-breeding
      sites of barn swallows Hirundo rustica tracked by geolocation.
AB  - Knowledge on whereabouts within the annual cycle of migratory species is
      prerequisite for many aspects in ecology and biological conservation. Spatial
      assignments of stable isotopes archived in tissues allows for later inference on
      sites where the specific tissue had been grown. It has been rarely tested whether
      spatial assignments match directly tracked non-breeding residences, especially
      for migratory songbirds. We here compare assignments of stable isotopes from
      feathers of Palaearctic Barn swallows Hirundo rustica with their African non
      breeding residence sites tracked by geolocation.Assignments based on delta2H,
      delta13C and delta15N isotope compositions delineate three main non-breeding
      regions: a main cluster in central Africa, a second in West Africa, and the third
      cluster in Northern Africa. Using delta13C, delta15N only, non-breeding sites
      ranged from clusters in West/Southwest Africa to South East Africa with a centre
      in Central Africa. The non-breeding areas (50% and 75% Kernel density estimates,
      KDE) of the birds tracked by geolocation stretched from West Africa via central
      Africa to southern Africa. We found little overlap of 0.3% (assuming a 1:1 odds
      ratio) to 1.4% (3:1 odds ratio) in the three element assignments and KDEs for
      only 2 and 13 individuals out of 32 birds. Assignment maps for two elements
      (delta13C, delta15N) and KDEs showed higher consistencies with an overlap of 3.6
      and 8.5% for 12 and 18 birds. We argue that the low matching between stable
      isotope assignments and non-breeding sites in our study arise from insufficient
      baseline data for Africa (concerning both isoscapes and specific discrimination
      functions). However, other factors like aerial foraging habit of the species, and
      a potential mismatch of non-breeding site location and the spatial origin of
      aerial plankton might further hamper accurate assignments. Finally we call for
      concerted analyses of tissues i.e. feathers and claws of birds which are grown at
      known sites across the continent and from species with various ecological
      requirements (diverse habitats, foraging behaviours, and diet compositions) to
      establish isoscapes for general applicability.

PMID- 30216346
TI  - A case-control study of breast cancer risk factors in 7,663 women in Malaysia.
AB  - BACKGROUND: Breast cancer risk factors have been examined extensively in Western
      setting and more developed Asian cities/countries. However, there are limited
      data on developing Asian countries. The purpose of this study was to examine
      breast cancer risk factors and the change of selected risk factors across birth
      cohorts in Malaysian women. METHODS: An unmatched hospital based case-control
      study was conducted from October 2002 to December 2016 in Selangor, Malaysia. A
      total of 3,683 cases and 3,980 controls were included in this study.
      Unconditional logistic regressions, adjusted for potential confounding factors,
      were conducted. The breast cancer risk factors were compared across four birth
      cohorts by ethnicity. RESULTS: Ever breastfed, longer breastfeeding duration, a
      higher soymilk and soy product intake, and a higher level of physical activity
      were associated with lower risk of breast cancer. Chinese had the lowest
      breastfeeding rate, shortest breastfeeding duration, lowest parity and highest
      age of first full term pregnancy. CONCLUSIONS: Our study shows that
      breastfeeding, soy intake and physical activity are modifiable risk factors for
      breast cancer. With the increasing incidence of breast cancer there is an urgent
      need to educate the women about lifestyle intervention they can take to reduce
      their breast cancer risk.

PMID- 30216348
TI  - Long length of stay at the emergency department is mostly caused by
      organisational factors outside the influence of the emergency department: A root
      cause analysis.
AB  - BACKGROUND: Emergency department (ED) crowding is common and associated with
      increased costs and negative patient outcomes. The aim of this study was to
      conduct an in-depth analysis to identify the root causes of an ED length of stay
      (ED-LOS) of more than six hours. METHODS: An observational retrospective record
      review study was conducted to analyse the causes for ED-LOS of more than six
      hours during a one-week period in an academic hospital in the Netherlands. Basic
      administrative data were collected for all visiting patients. A root cause
      analysis was conducted using the PRISMA-method for patients with an ED-LOS > 6
      hours, excluding children and critical care room presentations. RESULTS: 568
      patients visited the ED during the selected week (January 2017). Eighty-four
      patients (15%) had an ED-LOS > 6 hours and a PRISMA-analysis was performed in 74
      (88%) of these patients. 269 root causes were identified, 216 (76%) of which were
      organisational and 53 (22%) patient or disease related. 207 (94%) of the
      organisational factors were outside the influence of the ED. Descriptive
      statistics showed a mean number of 2,5 consultations, 59% hospital admissions or
      transfers and a mean age of 57 years in the ED-LOS > 6 hours group. For the total
      group, there was a mean number of 1,9 consultations, 29% hospital admissions or
      transfers and a mean age of 43 years. CONCLUSIONS: This study showed that the
      root causes for an increased ED-LOS were mostly organisational and beyond the
      control of the ED. These results confirm that interventions addressing the
      complete acute care chain are needed in order to reduce ED-LOS and crowding in
      ED's.

PMID- 30216349
TI  - What is the most appropriate method for coronary sinus cannulation? The
      telescopic method or the electrophysiologic method?
AB  - OBJECTIVES: The most challenging stage of cardiac resynchronization therapy (CRT)
      is coronary sinus cannulation (CS). The aim of this study was to compare coronary
      sinus cannulation techniques using electrophysiology catheters and coronary
      angiography catheters. METHODS: In this observational, retrospective and non
      randomized study, 87 patients who were eligible for CRT device implantation were
      screened at Kahramanmaras Sutcu Imam University Hospital between March 2014 and
      March 2018. Seventy-two patients who met the inclusion criteria were enrolled in
      the study. The study population was divided into 2 groups: the first group
      consisted of 36 patients whose coronary sinuses were cannulated via
      electrophysiology (EP) catheters and the second group included 36 patients who
      received coronary angiography catheters for coronary sinus cannulation. RESULTS:
      The two groups were similar in terms of the baseline characteristics of the
      patients. The total fluoroscopy time was less with cannulation using coronary
      angiography catheters. There were no differences between the two groups in terms
      of the amount of contrast material and the success of the operations.
      CONCLUSIONS: Coronary sinus catheterization using coronary angiography catheters
      significantly reduces fluoroscopy time in patients undergoing CRT.

PMID- 30216350
TI  - Outdoor particulate matter (PM10) exposure and lung cancer risk in the EAGLE
      study.
AB  - OBJECTIVE: Cohort studies in Europe, but not in North-America, showed an
      association between exposure to outdoor particulate matter with aerodynamic
      diameter <=10 MUm (PM10) and lung cancer risk. Only a case-control study on lung
      cancer and PM10 in South Korea has so far been performed. For the first time in
      Europe we analyzed quantitatively this association using a case-control study
      design in highly polluted areas in Italy. METHODS: The Environment And Genetics
      in Lung cancer Etiology (EAGLE) study, a population-based case-control study
      performed in the period 2002-2005 in the Lombardy Region, north-west Italy,
      enrolled 2099 cases and 2120 controls frequency-matched for area of residence,
      gender, and age. For this study we selected subjects with complete active and
      passive smoking history living in the same municipality since 1980 until study
      enrollment. Fine resolution annual PM10 estimates obtained by applying land use
      regression modeling to satellite data calibrated with fixed site monitor
      measurements were used. We assigned each subject the PM10 average estimates for
      year 2000 based on enrollment address. We used logistic regression models to
      calculate odds ratios (OR) and 95% confidence intervals (CI) adjusted for
      matching variables, education, smoking, and dietary and occupational variables.
      RESULTS: We included 3473 subjects, 1665 cases (1318 men, 347 women) and 1808
      controls (1368 men, 440 women), with PM10 individual levels ranging from 2.3 to
      53.8 MUg/m3 (mean: 46.3). We found increasing lung cancer risk with increasing
      PM10 category (P-value for trend: 0.04). The OR per 10 MUg/m3 was 1.28 (95% CI:
      0.95-1.72). The association appeared stronger for squamous cell carcinoma (OR
      1.44, 95% CI: 0.90-2.29). CONCLUSION: In a population living in highly polluted
      areas in Italy, our study added suggestive evidence of a positive association
      between PM10 exposure and lung cancer risk. This study emphasizes the need to
      strengthen policies to reduce airborne pollution.

PMID- 30216353
TI  - Improving classification of pollen grain images of the POLEN23E dataset through
      three different applications of deep learning convolutional neural networks.
AB  - In palynology, the visual classification of pollen grains from different species
      is a hard task which is usually tackled by human operators using microscopes. Its
      complete automatization would save a high quantity of resources and provide
      valuable improvements especially for allergy-related information systems, but
      also for other application fields as paleoclimate reconstruction, quality control
      of honey based products, collection of evidences in criminal investigations or
      fabric dating and tracking. This paper presents three state-of-the-art deep
      learning classification methods applied to the recently published POLEN23E image
      dataset. The three methods make use of convolutional neural networks: the first
      one is strictly based on the idea of transfer learning, the second one is based
      on feature extraction and the third one represents a hybrid approach, combining
      transfer learning and feature extraction. The results from the three methods are
      indeed very good, reaching over 97% correct classification rates in images not
      previously seen by the models, where other authors reported around 70.

PMID- 30216351
TI  - Bacteria richness and antibiotic-resistance in bats from a protected area in the
      Atlantic Forest of Southeastern Brazil.
AB  - Bats play key ecological roles, also hosting many zoonotic pathogens. Neotropical
      bat microbiota is still poorly known. We speculate that their dietary habits
      strongly influence their microbiota richness and antibiotic-resistance patterns,
      which represent growing and serious public health and environmental issue. Here
      we describe the aerobic microbiota richness of bats from an Atlantic Forest
      remnant in Southeastern Brazil, and the antibiotic-resistance patterns of
      bacteria of clinical importance. Oral and rectal cavities of 113 bats from Carlos
      Botelho State Park were swabbed. Samples were plated on 5% sheep blood and
      MacConkey agar and identified by the MALDI-TOF technique. Antibiotic
      susceptibility tests were performed using Kirby-Bauer's antibiotic disc diffusion
      technique.We identified 596 isolates at the genus level and tentatively to the
      species level. Proteobacteria was the most abundant phylum in all the dietary
      guilds, representing 87% of the total identified samples. The most common
      bacteria within bat individuals were Escherichia coli, Klebsiella oxytoca and
      Serratia marcescens, and within bat species were Serratia marcescens, Pseudomonas
      sp. and Staphylococcus sp. Frugivores presented the most diverse microbiota. In
      general, the antibiogram results indicated a low occurrence of resistance on
      eigth potentially pathogenic bacteria species. The resistance to antibiotics
      found on our samples was related mostly to the intrinsic resistance of the tested
      species.The low occurrence of resistant bacteria in our samples could be related
      to the well preserved environment where bats were caught. Once the major causes
      of resistance-acquiring are related to anthropic activites, the controlled access
      of tourists on certain regions of the Park seems to be effectively protecting the
      environment.

PMID- 30216352
TI  - Modeling and prediction of clinical symptom trajectories in Alzheimer's disease
      using longitudinal data.
AB  - Computational models predicting symptomatic progression at the individual level
      can be highly beneficial for early intervention and treatment planning for
      Alzheimer's disease (AD). Individual prognosis is complicated by many factors
      including the definition of the prediction objective itself. In this work, we
      present a computational framework comprising machine-learning techniques for 1)
      modeling symptom trajectories and 2) prediction of symptom trajectories using
      multimodal and longitudinal data. We perform primary analyses on three cohorts
      from Alzheimer's Disease Neuroimaging Initiative (ADNI), and a replication
      analysis using subjects from Australian Imaging, Biomarker & Lifestyle Flagship
      Study of Ageing (AIBL). We model the prototypical symptom trajectory classes
      using clinical assessment scores from mini-mental state exam (MMSE) and
      Alzheimer's Disease Assessment Scale (ADAS-13) at nine timepoints spanned over
      six years based on a hierarchical clustering approach. Subsequently we predict
      these trajectory classes for a given subject using magnetic resonance (MR)
      imaging, genetic, and clinical variables from two timepoints (baseline + follow
      up). For prediction, we present a longitudinal Siamese neural-network (LSN) with
      novel architectural modules for combining multimodal data from two timepoints.
      The trajectory modeling yields two (stable and decline) and three (stable, slow
      decline, fast-decline) trajectory classes for MMSE and ADAS-13 assessments,
      respectively. For the predictive tasks, LSN offers highly accurate performance
      with 0.900 accuracy and 0.968 AUC for binary MMSE task and 0.760 accuracy for 3
      way ADAS-13 task on ADNI datasets, as well as, 0.724 accuracy and 0.883 AUC for
      binary MMSE task on replication AIBL dataset.

PMID- 30216354
TI  - Towards national systems for continuous surveillance of antimicrobial resistance:
      Lessons from tuberculosis.
AB  - In a Perspective on the research article from Jacobson and colleagues, Amitabh
      Suthar and colleagues from the Centers for Disease Control and Prevention discuss
      the importance of and considerations for developing real-time and large-scale
      reporting systems for tracking and controlling antimicrobial resistance.

PMID- 30216355
TI  - Induction of obesity impairs reverse cholesterol transport in ob/ob mice.
AB  - OBJECTIVES: Obesity is an independent risk factor for cardiovascular disease.
      Reverse cholesterol transport (RCT) is an important cardioprotective mechanism.
      This study aimed to investigate RCT changes in a murine model of obesity.
      METHODS: Ob/ob and control mice were injected with [3H]-cholesterol-labelled
      macrophages and cholesterol accumulation quantified after 48 h. Ex vivo,
      cholesterol efflux and uptake were determined in hepatic and adipose tissues.
      RESULTS: Ob/ob mice had more labelled cholesterol in their plasma (86%, p<0.001),
      suggesting impaired RCT. SR-BI-mediated cholesterol efflux was elevated from
      ob/ob mice (serum, 33%; apoB-depleted plasma, 14%, p<0.01) and HDL-c were also
      higher (60%, p<0.01). Ex vivo it was found that cholesterol uptake was
      significantly lower into the livers and adipose tissue of ob/ob mice, compared to
      non-obese wildtype controls. Furthermore, ex vivo cholesterol efflux was reduced
      in ob/ob liver and adipose tissue towards apoA-I and HDL. Consistent with this,
      protein levels of SR-BI and ABCG1 were significantly lower in ob/ob hepatic and
      adipose tissue than in wildtype mice. Finally, labelled cholesterol
      concentrations were lower in ob/ob bile (67%, p<0.01) and faeces (76%, p<0.0001).
      CONCLUSION: Obesity causes impairment in RCT due to reduced plasma cholesterol
      uptake and efflux by hepatocytes and adipocytes. A reduction in the capacity for
      plasma cholesterol clearance may partly account for increased CVD risk with
      obesity.

PMID- 30216356
TI  - Who are the male partners of adolescent girls and young women in Swaziland?
      Analysis of survey data from community venues across 19 DREAMS districts.
AB  - BACKGROUND: Adolescent girls and young women (AGYW, ages 15-24) are at high risk
      of HIV in Swaziland. Understanding more about their male sexual partners can
      inform HIV prevention efforts for both. METHODS: Using the PLACE methodology
      across all 19 DREAMS implementation districts, 843 men ages 20-34 were surveyed
      between December 2016-February 2017. Surveys were conducted at 182 venues
      identified by community informants as places where AGYW and men meet/socialize.
      Descriptive and multivariate analyses examined characteristics and risk behaviors
      of male partners of AGYW. RESULTS: Men's average age was 25.7. Sixty-three
      percent reported female partners ages 15-19, and 70% reported partners ages 20-24
      in the last year; of those, 12% and 11% respectively had five or more such
      partners. Among the 568 male partners of AGYW, 36% reported consistent condom use
      with their current/last partner. Forty-two percent reported testing for HIV in
      the last year; 6% were HIV-positive, and of those, 97% were currently on
      treatment. One-third (37%) reported being circumcised; among uncircumcised, 81%
      were not considering it. In multivariate analyses, men who reported three or more
      AGYW partners in the last year were more likely to be HIV-positive (aOR 3.2, 95%
      CI 1.1,8.8). Men were also less likely to disclose their HIV status to adolescent
      versus older partners (aOR 0.6, 95% CI 0.4,0.9) and partners more than 5 years
      younger than themselves (aOR 0.6, 95% CI 0.4,0.9). Results also revealed
      relatively high unemployment and mobility, substantial financial
      responsibilities, and periodic homelessness. CONCLUSIONS: Most men identified
      through community venues reported relationships with AGYW, and these
      relationships demonstrated substantial HIV risk. Challenging life circumstances
      suggest structural factors may underlie some risk behaviors. Engaging men in HIV
      prevention and targeted health services is critical, and informant-identified
      community venues are promising intervention sites to reach high-risk male
      partners of AGYW.

PMID- 30216357
TI  - Shifting echo chambers in US climate policy networks.
AB  - Although substantial attention has focused on efforts by the new Administration
      to block environmental policies, climate politics have been contentious in the US
      since well before the election of Donald Trump. In this paper, we extend previous
      work on empirical examinations of echo chambers in US climate politics using new
      data collected on the federal climate policy network in summer 2016. We test for
      the similarity and differences at two points in time in homophily and echo
      chambers using Exponential Random Graph Models (ERGM) to compare new findings
      from 2016 to previous work on data from 2010. We show that echo chambers continue
      to play a significant role in the network of information exchange among policy
      elites working on the issue of climate change. In contrast to previous findings
      where echo chambers centered on a binding international commitment to emission
      reductions, we find that the pre-existing echo chambers have almost completely
      disappeared and new structures have formed around one of the main components of
      the Obama Administration's national climate policy: the Clean Power Plan. These
      results provide empirical evidence that science communication and policymaking at
      the elite level shift in relation to the policy instruments under consideration.

PMID- 30216358
TI  - On the development of gestural organization: A cross-sectional study of vowel-to
      vowel anticipatory coarticulation.
AB  - In the first years of life, children differ greatly from adults in the temporal
      organization of their speech gestures in fluent language production. However,
      dissent remains as to the maturational direction of such organization. The
      present study sheds new light on this process by tracking the development of
      anticipatory vowel-to-vowel coarticulation in a cross-sectional investigation of
      62 German children (from 3.5 to 7 years of age) and 13 adults. It focuses on
      gestures of the tongue, a complex organ whose spatiotemporal control is
      indispensable for speech production. The goal of the study was threefold: 1)
      investigate whether children as well as adults initiate the articulation for a
      target vowel in advance of its acoustic onset, 2) test if the identity of the
      intervocalic consonant matters and finally, 3) describe age-related developments
      of these lingual coarticulatory patterns. To achieve this goal, ultrasound tongue
      imaging was used to record lingual movements and quantify changes in
      coarticulation degree as a function of consonantal context and age. Results from
      linear mixed effects models indicate that like adults, children initiate vowels'
      lingual gestures well ahead of their acoustic onset. Second, while the identity
      of the intervocalic consonant affects the degree of vocalic anticipation in
      adults, it does not in children at any age. Finally, the degree of vowel-to-vowel
      coarticulation is significantly higher in all cohorts of children than in adults.
      However, among children, a developmental decrease of vocalic coarticulation is
      only found for sequences including the alveolar stop /d/ which requires finer
      spatiotemporal coordination of the tongue's subparts compared to labial and velar
      stops. Altogether, results suggest greater gestural overlap in child than in
      adult speech and support the view of a non-uniform and protracted maturation of
      lingual coarticulation calling for thorough considerations of the articulatory
      intricacies from which subtle developmental differences may originate.

PMID- 30216359
TI  - Rule-based generalization and peak shift in the presence of simple relational
      rules.
AB  - After discrimination learning between two stimuli that lie on a continuum,
      animals typically exhibit generalization on the basis of similarity to the
      physical features of the stimuli, often producing a peak-shifted gradient.
      However, post-discrimination generalization in humans usually resembles a
      monotonically increasing (e.g., linear) gradient that is better characterized as
      following a relational rule describing the difference between the stimuli. The
      current study tested whether rule-based generalization could be disrupted by
      reducing the applicability of a relational rule on test. We compared
      generalization following a difficult categorization task between a group who
      could use their rule consistently throughout test (Group Consistent), and a group
      who could only apply their rule effectively on 50% of test trials and thus could
      only use it inconsistently (Group Inconsistent). Across two experiments, a peak
      shift was found in the Inconsistent group and a monotonic gradient in the
      Consistent group. A post-hoc sequential analysis revealed that the Inconsistent
      group produced both peak-shifted and monotonic gradients as a function of whether
      or not the relevant rule was applicable on the previous trial. Reducing the
      applicability of a rule on test thus appeared to lead participants to revert to
      generalizing on the basis of similarity. Our results suggest that humans learn
      about the physical features of the stimuli alongside relational rules, and that
      rule- and similarity-based learning can interact in determining generalization.

PMID- 30216361
TI  - Histological architectural classification determines recurrence pattern and
      prognosis after curative hepatectomy in patients with hepatocellular carcinoma.
AB  - AIM: The clinical impact of pathological classification based on architectural
      pattern in hepatocellular carcinoma (HCC) remains elusive in spite of its well
      known and common feature. METHODS: The prognostic impact of pathological
      classification was examined with prospective database. Three hundred and eighty
      HCC patients who underwent curative hepatectomy as an initial treatment in
      Kumamoto University were enrolled as a test cohort. The outcome was confirmed
      with a validation cohort in Kyushu University. RESULTS: Macrotrabecular (macro-T)
      subtype (n = 38) and compact subtype (n = 43) showed similar biological and
      prognostic features. Both showed higher AFP level and worse overall survival than
      microrabecular (micro-T) subtype (n = 266). Multivariate analysis for overall
      survival revealed that DCP >= 40, multiple tumor and macro-T/compact subtype were
      associated with poor overall survival (risk ratio = 2.2, 1.6 and 1.6; p = 0.002,
      0.020, and 0.047, respectively). Of note, 32% of macro-T/compact subtype showed
      early recurrence within 1 year, which showed substantially low (5%) 5 year
      overall survival, whereas 16% of micro-T/PG subtype did. Twenty-one percent of
      macro-T/compact subtype showed multiple intrahepatic metastases (>= 4) or distant
      metastases, which resulted in non-curative treatment, whereas 5% of micro-T/PG
      subtype did. In validation cohort, macro-T/compact subtype was an independent
      predictor of worse overall survival. CONCLUSION: Macro-T/compact subtype is
      biologically discriminated from micro-T and PG subtypes due to its aggressive
      features and poor prognosis after curative treatment. Additional treatment with
      curative hepatectomy on Macro-T/compact subtype should be discussed because of
      high possibility of systemic residual cancer cell.

PMID- 30216360
TI  - HDL inflammatory index correlates with and predicts severity of organ failure in
      patients with sepsis and septic shock.
AB  - OBJECTIVE: High density lipoprotein (HDL) is important for defense against sepsis
      but becomes dysfunctional (Dys-HDL) during inflammation. We hypothesize that Dys
      HDL correlates with organ dysfunction (sequential organ failure assessment (SOFA)
      score) early sepsis. METHODS: A prospective cohort study of adult ED sepsis
      patients enrolled within 24 hours. RESULTS: Eighty eight patients were analyzed.
      Dys-HDL (expressed as HDL inflammatory index (HII)) correlated with SOFA at
      enrollment (r = 0.23, p = 0.024) and at 48 hours (r = 0.24, p = 0.026) but HII
      change over the first 48 hours did not correlate with change in SOFA (r = 0.06, p
      = 0.56). Enrollment HII was significantly different in patients with most severe
      organ failure (2.31, IQR 1.33-5.2) compared to less severe organ failure (1.81,
      IQR 1.23-2.64, p = 0.043). Change in HII over 48 hours was significantly
      different for in-hospital non-survivors (-0.45, IQR-2.6, -0.14 p = 0.015) and for
      28-day non-survivors (-1.12, IQR -1.52, 0.12, p = 0.044). In a multivariable
      linear regression equation (R2 = 0.13), for each unit HII increase, 48-hour SOFA
      increased by 0.72 (p = 0.009). CONCLUSION: HII correlated with SOFA and predicted
      48-hour SOFA score in early sepsis. Future studies are needed to delineate
      potential mechanisms. TRIAL REGISTRATION: NCT02370186. Registered February 24,
      2015.

PMID- 30216362
TI  - Prediction of early breast cancer patient survival using ensembles of hypoxia
      signatures.
AB  - BACKGROUND: Biomarkers are a key component of precision medicine. However, full
      clinical integration of biomarkers has been met with challenges, partly
      attributed to analytical difficulties. It has been shown that biomarker
      reproducibility is susceptible to data preprocessing approaches. Here, we
      systematically evaluated machine-learning ensembles of preprocessing methods as a
      general strategy to improve biomarker performance for prediction of survival from
      early breast cancer. RESULTS: We risk stratified breast cancer patients into
      either low-risk or high-risk groups based on four published hypoxia signatures
      (Buffa, Winter, Hu, and Sorensen), using 24 different preprocessing approaches
      for microarray normalization. The 24 binary risk profiles determined for each
      hypoxia signature were combined using a random forest to evaluate the efficacy of
      a preprocessing ensemble classifier. We demonstrate that the best way of merging
      preprocessing methods varies from signature to signature, and that there is
      likely no 'best' preprocessing pipeline that is universal across datasets,
      highlighting the need to evaluate ensembles of preprocessing algorithms. Further,
      we developed novel signatures for each preprocessing method and the risk
      classifications from each were incorporated in a meta-random forest model.
      Interestingly, the classification of these biomarkers and its ensemble show
      striking consistency, demonstrating that similar intrinsic biological information
      are being faithfully represented. As such, these classification patterns further
      confirm that there is a subset of patients whose prognosis is consistently
      challenging to predict. CONCLUSIONS: Performance of different prognostic
      signatures varies with pre-processing method. A simple classifier by unanimous
      voting of classifications is a reliable way of improving on single preprocessing
      methods. Future signatures will likely require integration of intrinsic and
      extrinsic clinico-pathological variables to better predict disease-related
      outcomes.

PMID- 30216363
TI  - Metabolic profiling of femoral muscle from rats at different periods of time
      after death.
AB  - Clarification of postmortem metabolite changes can help characterize the process
      of biological degradation and facilitate investigations of forensic casework,
      especially in the estimation of postmortem interval (PMI). Metabolomics can
      provide information on the molecular profiles of tissues, which can aid in
      investigating postmortem metabolite changes. In this study, liquid chromatography
      mass spectrometric (LC-MS) analysis was performed to identify the metabolic
      profiles of rat femoral muscle at ten periods of time after death within 168 h.
      The results obtained by reversed-phase liquid chromatography (RPLC)- and
      hydrophilic interaction liquid chromatography (HILIC)- electrospray ionization
      (ESI+/-) have revealed more than 16,000 features from all four datasets.
      Furthermore, 915 of these features were identified using an in-house database.
      Principal component analysis (PCA) demonstrated the time-specific features of
      molecular profiling at each period of time after death. Moreover, results from
      partial least squares projection to latent structures-discriminant analysis (PLS
      DA) disclosed a strong association of metabolic alterations of at least 59
      metabolites with the time since death, especially within 48 h after death, which
      expounds these metabolites as potential indicators in PMI estimation. Altogether,
      our results illustrate the potentiality of metabolic profiling in the evaluation
      of PMI and provide candidate metabolite markers with strong correlation with time
      since death for forensic purpose.

PMID- 30216364
TI  - Severity and properties of cardiac damage caused by Streptococcus pneumoniae are
      strain dependent.
AB  - Streptococcus pneumoniae is an opportunistic Gram-positive pathogen that can
      cause invasive disease. Recent studies have shown that S. pneumoniae is able to
      invade the myocardium and kill cardiomyocytes, with one-in-five adults
      hospitalized for pneumococcal pneumonia having a pneumonia-associated adverse
      cardiac event. Furthermore, clinical reports have shown up to a 10-year increased
      risk of adverse cardiac events in patients formerly hospitalized for pneumococcal
      bacteremia. In this study, we investigated the ability of nine S. pneumoniae
      clinical isolates, representing eight unique serotypes, to cause cardiac damage
      in a mouse model of invasive disease. Following intraperitoneal challenge of
      C57BL/6 mice, four of these strains (D39, WU2, TIGR4, and 6A-10) caused high
      grade bacteremia, while CDC7F:2617-97 and AMQ16 caused mid- and low-grade
      bacteremia, respectively. Three strains did not cause any discernible disease. Of
      note, only the strains capable of high-grade bacteremia caused cardiac damage, as
      inferred by serum levels of cardiac troponin-I. This link between bacteremia and
      heart damage was further corroborated by Hematoxylin & Eosin and Trichrome
      staining which showed cardiac cytotoxicity only in D39, WU2, TIGR4, and 6A-10
      infected mice. Finally, hearts infected with these strains showed varying
      histopathological characteristics, such as differential lesion formation and
      myocytolysis, suggesting that the mechanism of heart damage varied between
      strains.

PMID- 30216365
TI  - Preparation, formation mechanism, photocatalytic, cytotoxicity and antioxidant
      activity of sodium niobate nanocubes.
AB  - A hydrothermal method was employed to prepare the sodium niobate (NaNbO3)
      nanocubes. We executed time dependent experiments to illustrate the formation
      mechanism of sodium niobate nanocubes. It was observed that the morphology of
      NaNbO3 nanocubes was dependent on the reaction time and 12hr reaction time was
      found to be suitable. Morphology, composition, structure and optical properties
      of sodium niobate nanocubes were evaluated by scanning electron microscope, X-ray
      energy-dispersive spectrometer, X-ray diffraction and UV-visible diffuse
      reflectance spectrometer. The photocatalytic activity of sodium niobate was
      studied for photocatalytic hydrogen production. It was anticipated that the
      sodium niobate (NaNbO3) cubes exhibited good photocatalytic activity under UV
      light irradiation using lactic acid as sacrificial agent. The cytotoxicity
      activity of sodium niobate nanocubes was studied as well at different
      concentrations (5 mg/mL, 3 mg/mL, 1 mg/mL, and 0.25 mg/mL) against human colon
      colorectal carcinoma cell line (HCT116) by MTT assay and EC50 was found to be 1.9
      mg/mL. Sodium niobate proved to be a good DPPH free radical scavenging material,
      tested at different concentrations. It was noticed that peak intensity at 517 nm
      was decreased after 30 minute incubation, further supporting the antioxidant
      activity. This study will be useful for design and engineering of materials that
      can be used in biomedical applications and in photocatalysis.

PMID- 30216366
TI  - Origin and spread of Thoroughbred racehorses inferred from complete mitochondrial
      genome sequences: Phylogenomic and Bayesian coalescent perspectives.
AB  - The Thoroughbred horse breed was developed primarily for racing, and has a
      significant contribution to the qualitative improvement of many other horse
      breeds. Despite the importance of Thoroughbred racehorses in historical,
      cultural, and economical viewpoints, there was no temporal and spatial dynamics
      of them using the mitogenome sequences. To explore this topic, the complete
      mitochondrial genome sequences of 14 Thoroughbreds and two Przewalski's horses
      were determined. These sequences were analyzed together along with 151 previously
      published horse mitochondrial genomes from a range of breeds across the globe
      using a Bayesian coalescent approach as well as Bayesian inference and maximum
      likelihood methods. The racing horses were revealed to have multiple maternal
      origins and to be closely related to horses from one Asian, two Middle Eastern,
      and five European breeds. Thoroughbred horse breed was not directly related to
      the Przewalski's horse which has been regarded as the closest taxon to the all
      domestic horses and the only true wild horse species left in the world. Our
      phylogenomic analyses also supported that there was no apparent correlation
      between geographic origin or breed and the evolution of global horses. The most
      recent common ancestor of the Thoroughbreds lived approximately 8,100-111,500
      years ago, which was significantly younger than the most recent common ancestor
      of modern horses (0.7286 My). Bayesian skyline plot revealed that the population
      expansion of modern horses, including Thoroughbreds, occurred approximately 5,500
      11,000 years ago, which coincide with the start of domestication. This is the
      first phylogenomic study on the Thoroughbred racehorse in association with its
      spatio-temporal dynamics. The database and genetic history information of
      Thoroughbred mitogenomes obtained from the present study provide useful
      information for future horse improvement projects, as well as for the study of
      horse genomics, conservation, and in association with its geographical
      distribution.

PMID- 30216367
TI  - Development of a novel S. Typhi and Paratyphi A outer membrane vesicles based
      bivalent vaccine against enteric fever.
AB  - Salmonella Typhi and Salmonella Paratyphi A are the leading causative agents of
      enteric fever which cause morbidity and mortality worldwide. Currently, there is
      no combination vaccine which could protect infection from both the strains. In
      this paper, we are focusing on the development of a novel bivalent typhoidal
      Outer Membrane Vesicles (OMVs) based immunogen against enteric fever. We have
      isolated Salmonella Typhi and Paratyphi A OMVs and also characterized OMVs
      associated antigens. Then we immunized adult mice with three doses of our newly
      formulated bivalent immunogen orally (25 MUg/200 MUl). After three doses of oral
      immunization, we found our immunogen could significantly induce humoral response.
      We have also found serum IgG against LPS, Vi-polysaccharide etc. OMV immunization
      induces CD4, CD8 and CD19 population in immunized mice spleen. It also induces
      Th1 and Th17-cell mediated immunity. We also found bivalent OMVs immunization can
      prevent more than lethal dose of heterologous Salmonella strains mediated
      systemic infection in adult mice model. We determined that, the protective immune
      responses depend on the humoral and cell-mediated immune response. Furthermore,
      we have evaluated the mode of protective immune response carried out by anti-OMVs
      antibody by significantly inhibiting bacterial motility and mucin penetration
      ability. Taken together, these findings suggest that our bivalent immunogen could
      be used as a novel candidate vaccine against enteric fever.

PMID- 30216368
TI  - "Life continues": Patient, health care and community care workers perspectives on
      self-administered treatment for rifampicin-resistant tuberculosis in Khayelitsha,
      South Africa.
AB  - BACKGROUND: Self-administered treatment (SAT), a differentiated model of care for
      rifampicin-resistant tuberculosis (RR-TB), might address adherence challenges
      faced by patients and health care systems. This study explored patient, health
      care worker (HCW) and community care worker (CCW) perspectives on a SAT pilot
      programme in South Africa, in which patients were given medication to take at
      home with the optional support of a CCW. METHODS: We conducted a mixed-methods
      study from July 2016-June 2017. The quantitative component included semi
      structured questionnaires with patients, HCWs and CCWs; the qualitative component
      involved in-depth interviews with patients enrolled in the pilot programme.
      Interviews were conducted in isiXhosa, translated, transcribed and manually
      coded. RESULTS: Overall, 27 patients, 12 HCWs and 44 CCWs were enrolled in the
      quantitative component; nine patients were also interviewed. Of the 27 patients
      who completed semi-structured questionnaires, 22 were HIV-infected and 17
      received a monthly supply of RR TB treatment. Most HCWs and CCWs (10 and 32,
      respectively) understood the pilot programme; approximately half (n = 14) of the
      patients could not correctly describe the pilot programme. Overall, 11 and 41
      HCWs and CCWs reported that the pilot programme promoted treatment adherence.
      Additionally, 11 HCWs reported that the pilot programme relieved pressure on the
      clinic. Key qualitative findings highlighted the importance of a support person
      and how the flexibility of SAT enabled integration of treatment into their daily
      routines and reduced time spent in clinics. The pilot programme was also
      perceived to allow patients more autonomy and made it easier for them to manage
      side-effects. CONCLUSION: The SAT pilot programme was acceptable from the
      perspective of patients, HCWs and CCWs and should be considered as a
      differentiated model of care for RR-TB, particularly in settings with high
      burdens of HIV, in order to ease management of treatment for patients and health
      care providers.

PMID- 30216369
TI  - PKM2 and HIF-1alpha regulation in prostate cancer cell lines.
AB  - Prostate cancer (PCA) is one of the most common cancer types in men, with cancer
      progression being linked to hypoxia and the induction of hypoxia-inducible factor
      (HIF).We investigated the expression of pyruvate kinase M2 (PKM2), its regulation
      by HIF isoforms 1alpha and 2alpha, and its role in HIF stabilization. We
      additionally examined cell survival in the prostate cancer cell lines PC3 and
      LNCaP under severe hypoxic (0.1% O2) and normoxic (20% O2) conditions. qRT-PCR
      showed higher up-regulation of PKM2 mRNA expression in LNCaP cells than in PC3
      cells, while western blotting showed that PKM2 protein levels were up-regulated
      only in LNCaP cells. Inhibition of HIF-1alpha and HIF-2alpha by small interfering
      RNA (si-RNA) demonstrated HIF-1alpha dependent up-regulation of PKM2 at the mRNA
      and protein levels in LNCaP cells. PKM2 inhibition by si-RNA significantly
      decreased hypoxia-response element (HRE) activation in a gene reporter assay and
      down-regulated HIF-1alpha target vascular endothelial growth factor (VEGF) mRNA
      expression in PC3 cells, whereas HIF-1alpha protein levels were not significantly
      reduced. Additionally, PKM2 inhibition significantly reduced clonogenic survival
      in both cell lines in a colony formation assay. Prolyl hydroxylase 3 (PHD3) mRNA
      expression was up-regulated in both cell lines. It has been shown that PKM2
      expression is regulated by HIF-1alpha and that PKM2 favors HIF-1alpha
      transactivation under mild (1% O2) but not severe (0.1% O2) hypoxic conditions,
      and some of our findings are consistent with these previous results. However,
      this mechanism was not fully observed in our studied cell lines, as PKM2
      regulation and HIF-1alpha stabilization at the transactivation level occurred
      under severe hypoxic conditions. This discrepancy suggests that tumor tissue
      origin and cell type influence this model. Our findings expand the current
      knowledge of the mechanisms of PCA regulation, and would be important in
      developing novel therapeutic strategies.

PMID- 30216370
TI  - Enhanced biofilm prevention activity of a SPLUNC1-derived antimicrobial peptide
      against Staphylococcus aureus.
AB  - SPLUNC1 is a multifunctional protein of the airway with antimicrobial properties.
      We previously reported that it displayed antibiofilm activities against P.
      aeruginosa. The goal of this study was to determine whether (1) the antibiofilm
      property is broad (including S. aureus, another prevalent organism in cystic
      fibrosis); (2) the alpha4 region is responsible for such activity; and (3), if
      so, this motif could be structurally optimized as an antimicrobial peptide with
      enhanced activities. We used S. aureus biofilm-prevention assays to determine
      bacterial biomass in the presence of SPLUNC1 and SPLUNC1Deltaalpha4 recombinant
      proteins, or SPLUNC1-derived peptides (alpha4 and alpha4M1), using the well
      established crystal-violet biofilm detection assay. The SPLUNC1Deltaalpha4 showed
      markedly reduced biofilm prevention compared to the parent protein. Surprisingly,
      the 30-residue long alpha4 motif alone demonstrated minimal biofilm prevention
      activities. However, structural optimization of the alpha4 motif resulted in a
      modified peptide (alpha4M1) with significantly enhanced antibiofilm properties
      against methicillin-sensitive (MSSA) and-resistant (MRSA) S. aureus, including
      six different clinical strains of MRSA and the well-known USA300. Hemolytic
      activity was undetectable at up to 100MUM for the peptides. The data warrant
      further investigation of alpha4-derived AMPs to explore the potential application
      of antimicrobial peptides to combat bacterial biofilm-related infections.

PMID- 30216371
TI  - Rapid detection of NDM, KPC and OXA-48 carbapenemases directly from positive
      blood cultures using a new multiplex immunochromatographic assay.
AB  - : Bloodstream infections caused by carbapenemase-producing Enterobacteriaceae
      (CPE) are associated with treatment failure and increased mortality. Detection of
      CPE from blood cultures (BC) by standard methods takes 16-72 hours, which can
      delay the initiation of appropriate antimicrobial therapy and compromise patient
      outcome. In the present study, we developed and evaluated a new method for the
      rapid detection of carbapenemases directly from positive BC using a new multiplex
      immunochromatographic test (ICT). The new ICT was assessed using 170 molecularly
      characterized Enterobacteriaceae clinical isolates including 126 CPE (OXA-48-like
      (N = 79), KPC (N = 18) and NDM (N = 29)). After spiking with bacteria and
      incubation in a BC system, blood from positive BC bottles was hemolyzed, bacteria
      concentrated by centrifugation and lysed. The lysate was transferred to the
      RESIST-3 O.K.N. ICT (Coris BioConcept, Gembloux, Belgium), which detects OXA-48
      like, KPC and NDM carbapenemases. The final results of the ICT were read when
      they became positive, at the latest after 15 min. All CPE isolates (126/126) were
      correctly detected with the new protocol (100% sensitivity, 100% specificity).
      There was perfect concordance between ICT results and molecular characterization.
      Total time to result was 20-45 min. CONCLUSIONS: This proof-of-principle study
      demonstrates that with the newly developed method, OXA-48-like, KPC and NDM
      carbapenemases can be reliably detected directly from positive BC bottles. The
      new method is more rapid than other currently available assays and can be
      performed in any routine microbiology laboratory. This can help to rapidly
      identify patients with CPE BSI and optimize the management of patients with these
      difficult-to-treat infections. Further studies are needed to assess the
      performance of the ICT in routine diagnostics.

PMID- 30216372
TI  - Respiratory modulation of cognitive performance during the retrieval process.
AB  - Recent research suggests that cognitive performance might be altered by the
      respiratory-synchronized activity generated in the brain. Previous human studies,
      however, have yielded inconsistent results when assessing task performance during
      distinct respiratory phases (inspiratory phase vs. expiratory phase). We
      therefore tested whether cognitive performance was regulated based on the timing
      of breathing components (e.g., expiratory-to-inspiratory (EI) phase transition)
      during the retrieval process. To determine the role of respiration in
      performance, the present study employed healthy subjects (n = 18) in a delayed
      matching-to-sample visual recognition task where a test cue was given in the
      respiratory phase-locked (Phased) or regularly paced (Non-phased) presentation
      paradigm. During the Phased session but not during the Non-phased session, the
      response time (RT) of the task increased by 466 ms (p = 0.003), and accuracy
      decreased by 21.4% (p = 0.004) when the retrieval process encompassed the EI
      transition. Breathing-dependent changes were particularly prominent when the EI
      transition occurred during the middle step of the retrieval process. Meanwhile,
      changes in the RT and accuracy were not observed when the retrieval process
      encompassed the inspiratory-to-expiratory phase transition. This is the first
      time that a certain phase transition in the respiratory cycle has been shown to
      modulate performance on a time scale of several seconds in a cognitive task. We
      propose that attenuation of these breathing-dependent cognitive fluctuations
      might be crucial for the maintenance and stability of successful performance in
      daily life and sports.

PMID- 30216373
TI  - Cardiovascular biomarkers and risk of low-energy fractures among middle-aged men
      and women-A population-based study.
AB  - BACKGROUND: Low-energy fractures are a growing health challenge as their
      incidence increases with advancing age. As cardiovascular instability may be
      associated with higher likelihood of traumatic falls, we aimed to investigate the
      associations between four cardiovascular biomarkers and the risk of low-energy
      fractures in a middle-aged population. METHODS: A total of 5291 individuals from
      the prospective Malmo Diet and Cancer (MDC) study (mean age, 57 years; 59% women)
      with data on baseline levels of four cardiovascular biomarkers: mid-regional
      fragment of pro-adrenomedullin-peptide (MR-pro-ADM), mid-regional-fragment of pro
      atrial-natriuretic-peptide (MR-proANP), N-terminal pro-brain natriuretic peptide
      (NT-pro-BNP) and C-terminal-pro-arginine-vasopressin (CT-pro-AVP/Copeptin) were
      included. The associations between biomarker levels and first incident low-energy
      fracture were tested in Cox proportional-hazard models, taking potential
      interactions and traditional risk factors into account. RESULTS: Participants
      were followed for a median time of 21.0 years, during which 1002 subjects (19%)
      experienced at least one low-energy fracture. Subjects with incident fracture
      were older, more likely to be women, had lower BMI and higher prevalence of
      previous fractures. Among biomarkers, there was a significant interaction between
      gender and MR-pro-ADM on the risk of fracture (p = 0.002). MR-pro-ADM predicted
      fractures in men only (hazard ratio, 1.23; 95% CI 1.09-1.40; p = 0.001), whereas
      there was no association among women. Levels of MR-pro-ANP, NT-pro-BNP and CT-pro
      AVP did not predict fractures. CONCLUSIONS: Higher circulating levels of MR-pro
      ADM predict low-energy fractures among middle-aged-men, whereas levels of MR-pro
      ANP, NT-pro-BNP and CT-pro-AVP are not associated with increased fracture risk.
      Further controlled studies should test the hypothesis whether MR-pro-ADM may
      improve prediction of bone fractures.

PMID- 30216374
TI  - A safe, low-cost, easy-to-use 3D camera platform to assess risk of obstructed
      labor due to cephalopelvic disproportion.
AB  - Cephalopelvic disproportion (CPD)-related obstructed labor is accountable for 3
      8% of the maternal deaths worldwide. The consequence of CPD-related obstructive
      labor in the absence of a Caesarian section (C/S) is often maternal or perinatal
      mortality or morbidity to the mother and/or the infant. Accurate and timely
      referral of at-risk mothers to health facilities where C/S is a delivery option
      could reduce maternal mortality in the developing world. The goal of this work
      was to develop and test the feasibility of a safe, low-cost, easy-to-use,
      portable tool, using a Microsoft Kinect 3D camera, to identify women at risk for
      obstructed labor due to CPD. Magnetic resonance imaging (MRI) scans, 3D camera
      imaging, anthropometry and clinical pelvimetry were collected and analyzed from
      women 18-40 years of age, at gestational age >=36+0 weeks with previous C/S due
      to CPD (n = 43), previous uncomplicated vaginal deliveries (n = 96), and no
      previous obstetric history (n = 148) from Addis Ababa, Ethiopia. Novel and
      published CPD risk scores based on anthropometry, clinical pelvimetry, MRI, and
      Kinect measurements were compared. Significant differences were observed in most
      anthropometry, clinical pelvimetry, MRI and Kinect measurements between women
      delivering via CPD-related C/S versus those delivering vaginally. The area under
      the receiver-operator curve from novel CPD risk scores base on MRI-, Kinect-, and
      anthropometric-features outperformed novel CPD risk scores based on clinical
      pelvimetry and previously published indices for CPD risk calculated from these
      data; e.g., pelvic inlet area, height, and fetal-pelvic index. This work
      demonstrates the feasibility of a 3D camera-based platform for assessing CPD risk
      as a novel, safe, scalable approach to better predict risk of CPD in Ethiopia and
      warrants the need for further blinded, prospective studies to refine and validate
      the proposed CPD risk scores, which are required before this method can be
      applied clinically.

PMID- 30216375
TI  - Social inequalities in health and mental health in France. The results of a 2010
      population-based survey in Paris Metropolitan Area.
AB  - The present study aimed to assess socioeconomic inequalities in general and
      mental health, depression and substance use disorders (daily tobacco use,
      hazardous alcohol use). Data from the 2010 SIRS (French acronym for Health,
      Inequalities, and Social Ruptures) study, which is deemed to be representative of
      the French-speaking adult population living in the Paris Metropolitan Area, were
      analysed. Different socioeconomic position indicators were selected: education,
      income and perceived financial status. Absolute measures (the slope index of
      inequality (SII)) and relative measures (the odds ratio (OR) and relative index
      of inequality (RII)) of health inequalities were used. The OR, RII and SII were
      adjusted for age, household type and migration characteristics and all analyses
      were performed separately for men and women. The study included 3,006 adults. The
      results showed significant relative and absolute socioeconomic inequalities in
      general, mental health and depression for all socioeconomic position indicators
      considered (education, income, and perceived financial status). The absolute
      inequalities were greater for women than for men. Strongest inequalities were
      observed by perceived financial status for men and women. Education seemed to
      play a stronger role in inequalities for women, whereas, for men, income seemed
      to play a stronger role. Only few socioeconomic inequalities were found in daily
      tobacco use, while a reversed gradient was observed for hazardous alcohol use. We
      hope that these results will be regularly re-evaluated and compared across time
      in order to monitor socioeconomic inequalities in health.

PMID- 30216376
TI  - A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus.
AB  - Infectious bronchitis virus (IBV) affects poultry respiratory, renal and
      reproductive systems. Currently the efficacy of available live attenuated or
      killed vaccines against IBV has been challenged. We designed a novel IBV vaccine
      alternative using a highly innovative platform called Self-Assembling Protein
      Nanoparticle (SAPN). In this vaccine, B cell epitopes derived from the second
      heptad repeat (HR2) region of IBV spike proteins were repetitively presented in
      its native trimeric conformation. In addition, flagellin was co-displayed in the
      SAPN to achieve a self-adjuvanted effect. Three groups of chickens were immunized
      at four weeks of age with the vaccine prototype, IBV-Flagellin-SAPN, a negative
      control construct Flagellin-SAPN or a buffer control. The immunized chickens were
      challenged with 5x104.7 EID50 IBV M41 strain. High antibody responses were
      detected in chickens immunized with IBV-Flagellin-SAPN. In ex vivo proliferation
      tests, peripheral mononuclear cells (PBMCs) derived from IBV-Flagellin-SAPN
      immunized chickens had a significantly higher stimulation index than that of
      PBMCs from chickens receiving Flagellin-SAPN. Chickens immunized with IBV
      Flagellin-SAPN had a significant reduction of tracheal virus shedding and lesser
      tracheal lesion scores than did negative control chickens. The data demonstrated
      that the IBV-Flagellin-SAPN holds promise as a vaccine for IBV.

PMID- 30216378
TI  - Evolution of dynamic, biochemical, and morphological parameters in hypothermic
      machine perfusion of human livers: A proof-of-concept study.
AB  - INTRODUCTION: Hypothermic machine perfusion (HMP) is increasingly investigated as
      a means to assess liver quality, but data on viability markers is inconsistent
      and the effects of different perfusion routes and oxygenation on perfusion
      biomarkers are unclear. METHODS: This is a single-centre, randomised, multi-arm,
      parallel study using discarded human livers for evaluation of HMP using arterial,
      oxygen-supplemented venous and non-oxygen-supplemented venous perfusion. The
      study included 2 stages: in the first stage, 25 livers were randomised into
      static cold storage (n = 7), hepatic artery HMP (n = 10), and non-oxygen
      supplemented portal vein HMP (n = 8). In the second stage, 20 livers were
      randomised into oxygen-supplemented and non-oxygen-supplemented portal vein HMP
      (n = 11 and 9, respectively). Changes in dynamic, biochemical, and morphologic
      parameters during 4-hour preservation were compared between perfusion groups, and
      between potentially transplantable and non-transplantable livers. RESULTS: During
      arterial perfusion, resistance was higher and flow was lower than venous
      perfusion (p = 0.001 and 0.01, respectively); this was associated with higher
      perfusate markers during arterial perfusion (p>0.05). Supplementary oxygen did
      not cause a significant alteration in the studied parameters. Morphology was
      similar between static and dynamic preservation groups. Perfusate markers were 2
      fold higher in non-transplantable livers (p>0.05). CONCLUSIONS: Arterial only
      perfusion might not be adequate for graft perfusion. Hepatocellular injury
      markers are accessible and easy to perform and could offer insight into graft
      quality, but large randomised trials are needed to identify reliable quality
      assessment biomarkers.

PMID- 30216377
TI  - Liver elasticity in healthy individuals by two novel shear-wave elastography
      systems-Comparison by age, gender, BMI and number of measurements.
AB  - OBJECTIVE: Establishing normal liver stiffness (LS) values in healthy livers is a
      prerequisite to differentiate normal from pathological LS values. Our aim was to
      define normal LS using two novel elastography methods head-to-head and to assess
      the number of measurements, variability and reproducibility. MATERIALS AND
      METHODS: We evaluated shear wave elastography (SWE) methods integrated in Samsung
      RS80A and GE S8 by obtaining LS measurements (LSM) in 100 healthy subjects (20-70
      years). Transient Elastography (TE) was used as reference method. Data were
      analyzed according to age, sex, BMI and 5 vs. 10 measurements. All subjects
      underwent B-mode ultrasound examination and lab tests to exclude liver pathology.
      Interobserver variation was evaluated in a subset (n = 24). RESULTS: Both methods
      showed excellent feasibility, measuring LS in all subjects. LSM-mean for GE S8 2D
      SWE was higher compared to TE (4.5+/-0.8 kPa vs. 4.2+/-1.1, p<0.001) and Samsung
      RS80A (4.1+/-0.8 kPa, p<0.001). Both methods showed low intra- and interobserver
      variation. LSM-mean was significantly higher in males than females using 2D-SWE,
      while a similar trend for Samsung SWE did not reach significance. No method
      demonstrated statistical significant difference in LSM across age and BMI groups
      nor between LSM-mean based on 5 vs. 10 measurements. CONCLUSION: LSM was
      performed with high reproducibility in healthy adult livers. LSM-mean was
      significantly higher for GE S8 2D-SWE compared to Samsung RS80A and TE in healthy
      livers. Males had higher LSM than females. No method demonstrated statistical
      significant difference in LSM-mean across age- and non-obese BMI groups. Our
      results indicate that five LSM may be sufficient for reliable results.

PMID- 30216379
TI  - Influence of construction and demolition waste on fitness and community structure
      of cicada nymphs: New bioindicators of soil pollution.
AB  - Construction and demolition (C&D) waste is a novel, widespread environmental
      stress that negatively affects environment, organisms and ecosystem. Yet effects
      of cumulative consequences of C&D waste on the fitness and community structure of
      most underground insects remain unclear. With relatively sessile life underground
      lasting several years, cicadas can be an important aspect in forest nutrient
      cycles. Whether cicada nymphs are easily affected by C&D waste, and whether they
      have evolved any adaptations to cope with the adverse environments merit
      exploration. Here, we investigated the biodiversity, community structure,
      population dynamics and morphology of cicada nymphs in both uncontaminated and
      contaminated habitats by C&D waste in Guanzhong Plain, China since 2011. In
      total, 1,573 cicada nymphs were collected from 2011 to 2015, including 62
      malformed nymphs. The malformed nymphs can be divided into three types:
      physically damaged individuals (still alive) (3.2%), fungus-infected individuals
      (dead) (64.5%), and bacterium-infected individuals (dead) (32.3%). The proportion
      of malformed nymphs increased year by year in the habitats contaminated by C&D
      waste. In the uncontaminated habitats, although no significant differences of
      population density among the investigated years were observed, yet there was a
      distinct increasing trend of population of Meimuna mongolica, whereas populations
      of both Cryptotympana atrata and Platypleura kaempferi distinctly decreased. This
      indicates that M. mongolica is possibly evolving into the most dominant species
      in the ecological niche when it competes with other sympatric species, but more
      researches are needed to establish whether there is a shift in the species
      composition of cicadas. In the habitats contaminated by C&D waste, a higher ratio
      of malformed individuals and a decline of population of both M. mongolica and C.
      atrata were revealed; P. kaempferi was not found in the contaminated habitats,
      indicating a weaker resistance of this species against C&D waste. The negative
      responses of cicada nymphs to C&D waste have significant implications for the
      habitat destruction. Cicada nymphs may be suitable bioindicators for underground
      habitat-quality monitoring, as merits further research to reveal the association
      between the magnitude of C&D waste contamination with the fitness and population
      dynamics of cicada nymphs.

PMID- 30216380
TI  - Dissecting cancer heterogeneity based on dimension reduction of transcriptomic
      profiles using extreme learning machines.
AB  - It is becoming increasingly clear that major malignancies such as breast,
      colorectal and gastric cancers are not single disease entities, but comprising
      multiple cancer subtypes of distinct molecular properties. Molecular subtyping
      has been widely used to dissect inter-tumor biological heterogeneity, in relation
      to clinical outcomes. A key step of this methodology is to perform unsupervised
      classification of gene expression profiles, which, however, often suffers
      challenges of high-dimensionality, feature redundancy as well as noise and
      irrelevant information. To overcome these limitations, we propose ELM-CC, which
      employs hidden observation features obtained from extreme learning machines
      (ELMs) for cancer classification. To demonstrate the effectiveness and
      usefulness, we applied ELM-CC for gastric and ovarian cancer subtyping. Comparing
      with the widely-used consensus clustering method, our approach demonstrated much
      better clustering performance and identified molecular subtypes that are much
      more clinically relevant.

PMID- 30216381
TI  - Improving knowledge of psychotropic prescribing in people with Intellectual
      Disability in primary care.
AB  - PURPOSE: People with Intellectual disability (ID) are likely to be prescribed
      psychotropic medication particularly antipsychotics without a clear clinical
      indication. This has given rise to a national initiative in the UK to stop
      overprescribing medication in this vulnerable population. While the goals are
      simple it is unclear if specialist ID services or primary care services in the UK
      should look to lead. Further, it is uncertain if primary care practitioners (GPs)
      can be systematically educated of the latest good practice developments and
      concerns in this specialised area. This study surveyed the knowledge level of a
      sample of GPs in Cornwall UK (county of 538,000) post a structured tutorial on
      psychotropic medication and people with ID. METHODS: A 21 item questionnaire was
      delivered in meetings organised for all the county GPs a year after a talk given
      to the same demographic. The questionnaire conducted an assessment of the
      knowledge of national guidance on use of psychotropic medication in ID based on
      the subjects covered in the tutorial. RESULTS: Of the 60 expected GP participants
      the tutorial was attended by 44 GPs (73%) and the follow up meeting by 42 (70%).
      Ninety percent GPs in the follow up meeting filled the questionnaire. For 16
      questions, more than 80% GPs gave correct responses whereas five questions
      attracted a correct answer from less than 80%. Majority of the GPs felt
      psychotropic medication management in people with ID should be specialist led.
      CONCLUSIONS: GPs' knowledge of issues relevant to prescribing in people with ID
      benefitted from the tutorial. However a clear need for the psychotropic
      medication management to be delivered via specialist care emerged. This raises
      issues of resource allocation and debate on whether people with ID require
      specialist provision due to lack of ability in main stream primary care to manage
      their needs.

PMID- 30216382
TI  - Investigating the impact of a motion capture system on Microsoft Kinect v2
      recordings: A caution for using the technologies together.
AB  - Microsoft Kinect sensors are considered to be low-cost popular RGB-D sensors and
      are widely employed in various applications. Consequently, several studies have
      been conducted to evaluate the reliability and validity of Microsoft Kinect
      sensors, and noise models have been proposed for the sensors. Several studies
      utilized motion capture systems as a golden standard to assess the Microsoft
      Kinect sensors, and none of them reported interference between Kinect sensors and
      motion capture systems. This study aimed to investigate possible interference
      between a golden standard (i.e., Qualisys) and Microsoft Kinect v2. The depth
      recordings of Microsoft Kinect sensors were processed to estimate the intensity
      of interference. A flat non-reflective surface was utilized, and smoothness of
      the surface was measured using Microsoft Kinect v2 in absence and presence of an
      active motion capture system. The recording was repeated in five different
      distances. The results indicated that Microsoft Kinect v2 is distorted by the
      motion capture system and the distortion is increasing by increasing distance
      between Kinect and region of interest. Regarding the results, it can be concluded
      that the golden standard motion capture system is robust against interference
      from the Microsoft Kinect sensors.

PMID- 30216383
TI  - Dogs are the main species involved in animal-vehicle collisions in southern
      Spain: Daily, seasonal and spatial analyses of collisions.
AB  - Animal-vehicle collisions have become a serious traffic safety issue. Collisions
      have steadily increased over the last few decades, as have their associated socio
      economic costs. Here, we explore the spatial and temporal patterns of animal
      vehicle collisions reported to authorities in the province of Seville, southern
      Spain. Most animal-vehicle collisions involved domestic animals (>95%),
      particularly dogs (>80%), a pattern that sharply contrasts with that found in
      other Spanish and European regions, where collisions are mostly caused by game
      species. Dog-vehicle collisions were related to the traffic intensity of the
      roads and they were more frequent around dawn and dusk, coinciding with the peaks
      of activity of dogs. This pattern was consistent throughout the week, although on
      weekends there were fewer collisions due to lower traffic density at those times.
      These findings suggest that the aggregation of dog-vehicle collisions around
      twilight likely resulted from a combined effect of the activity peaks of dogs and
      traffic density. Seasonally, collisions increased in autumn and winter,
      coinciding with the period of intense hunting activity in the region. Further,
      during autumn and winter, rush hour partly overlaps with twilight due to longer
      nights in comparison with summer and spring, which may contribute to the
      increased rate of dog-vehicle collisions in these seasons. Spatially, satellite
      images of nighttime lights showed that dog-vehicle collisions were clustered near
      urban areas. Overall, the high incidence of stray dogs involved in animal-vehicle
      collisions highlights a road safety issue with this type of animals in the
      region.

PMID- 30216384
TI  - Circular RNA identified from Peg3 and Igf2r.
AB  - Circular RNA is a newly discovered class of non-coding RNA generated through the
      back-splicing of linear pre-mRNA. In the current study, we characterized two
      circular RNAs that had been identified through NGS-based 5'RACE experiments.
      According to the results, the Peg3 locus contains a 214-nucleotide-long circular
      RNA, circPeg3, that is detected in low abundance from the neonatal brain, lung
      and ovary. In contrast, the Igf2r locus contains a group of highly abundant
      circular RNAs, circIgf2r, showing multiple forms with various exon combinations.
      In both cases, the expression patterns of circPeg3 and circIgf2r among individual
      tissues are quite different from their linear mRNA counterparts. This suggests
      potential unique roles played by the identified circular RNAs. Overall, this
      study reports the identification of novel circular RNAs specific to mammalian
      imprinted loci, suggesting that circular RNAs are likely involved in the function
      and regulation of imprinted genes.

PMID- 30216385
TI  - Eye tracking cognitive load using pupil diameter and microsaccades with fixed
      gaze.
AB  - Pupil diameter and microsaccades are captured by an eye tracker and compared for
      their suitability as indicators of cognitive load (as beset by task difficulty).
      Specifically, two metrics are tested in response to task difficulty: (1) the
      change in pupil diameter with respect to inter- or intra-trial baseline, and (2)
      the rate and magnitude of microsaccades. Participants performed easy and
      difficult mental arithmetic tasks while fixating a central target. Inter-trial
      change in pupil diameter and microsaccade magnitude appear to adequately
      discriminate task difficulty, and hence cognitive load, if the implied causality
      can be assumed. This paper's contribution corroborates previous work concerning
      microsaccade magnitude and extends this work by directly comparing microsaccade
      metrics to pupillometric measures. To our knowledge this is the first study to
      compare the reliability and sensitivity of task-evoked pupillary and
      microsaccadic measures of cognitive load.

PMID- 30216386
TI  - Female American black bears do not alter space use or movements to reduce
      infanticide risk.
AB  - Infanticide occurs in a variety of animal species and infanticide risk has large
      implications for the evolution of behavior. Further, the sex hypothesis of sexual
      segregation predicts that for species in which infanticide occurs, females with
      dependent young will avoid males to reduce risk of sexually-selected infanticide.
      Infanticide risk-avoidance behavior has been studied primarily in social species,
      but also occurs in some solitary species. We used generalized linear mixed models
      to determine if space use and movements of female American black bears (Ursus
      americanus) during the breeding season were consistent with the sex hypothesis of
      sexual segregation in the Upper Peninsula of Michigan, USA. Space use and
      movements of female black bears (n = 16) were not consistent with avoidance
      behavior to reduce sexually-selected infanticide risk. Females with cubs occupied
      core areas (mean = 4.64 km2, standard error [SE] = 1.28) and home ranges (mean =
      19.46 km2, SE = 5.10) of similar size to females without cubs (core area [mean =
      4.11 km2, SE = 0.59]; home range [mean = 16.07 km2, SE = 2.26]), and those core
      areas and home ranges were not in areas with lesser relative probability of male
      use. Additionally, females with cubs did not reduce movements during times of day
      when male movements were greatest. As female bears do avoid potentially
      infanticidal males in populations with greater levels of infanticide, female
      black bears may exhibit variation in avoidance behavior based on the occurrence
      of infanticide.

PMID- 30216387
TI  - Lipid profile changes in erythrocyte membranes of women with diagnosed GDM.
AB  - Gestational diabetes mellitus (GDM) is a glucose intolerance that begins or is
      first recognized during pregnancy. It is currently a growing health problem
      worldwide affecting from 1% to 14% of all pregnant women depending on racial and
      ethnic group as well as the diagnostic and screening criteria. Our preliminary
      study aimed at investigating the erythrocyte membrane fatty acid profiles of
      pregnant women, in particular with diagnosed with gestational diabetes mellitus
      (GDM), and with normal glucose tolerant (NGT) pregnant women as a control group.
      The study group comprised 43 pregnant women, 32 of whom were diagnosed with GDM
      according to the WHO criteria, and 11 with normal glucose tolerance. The
      erythrocyte membrane phospholipids were obtained according to the Folch
      extraction procedure. Fatty acids (FA) were analyzed by gas chromatography (GC)
      as the corresponding fatty acid methyl esters (FAME). A cluster of 14 fatty acids
      identified contained >98% of the recognized peaks in the GC analysis. The
      analysis of fatty acids from erythrocytes revealed important differences between
      GDM and NGT women in the third trimester, and the results were correlated with
      biochemical data. Among the 14 measured FA representing the membrane lipidomic
      profile, the levels of three saturated FA (myristic, palmitic, stearic acids)
      tended to decrease in GDM patients, with the percentage content of stearic acid
      significantly changed. The relative content of monounsaturated fatty acids (MUFA)
      tended to increase, in particular the oleic acid and vaccenic acid contents were
      significantly increased in erythrocyte membranes of the GDM group in comparison
      with the NGT group. The GDM group demonstrated higher sapienic acid levels (+29%)
      but this change was not statistically significant. This study revealed
      association between an impaired cis-vaccenic acid concentration in erythrocytes
      membrane and GDM development. No significant changes of polyunsaturated fatty
      acids (PUFA) were observed in GDM and NGT erythrocytes. We postulate, basing on
      the differences between the GDM and NGT lipidomic profiles, that stearic and cis
      vaccenic acids can be considered as dual biomarkers of specific SFA-MUFA
      conversion pathway, involving the coupling of delta-9 desaturase and elongase
      enzymes. Our results indicate that the SFA-MUFA families may be involved in the
      pathophysiology of metabolic diseases such as GDM, but the further studies are
      needed to confirm our hypothesis. In conclusion, the erythrocyte membranes of GDM
      women undergo remodeling resulting in abnormal fatty acid profiles, which are
      reflection of the long-term status of organism and can have great impact on both
      the mother and her offspring.

PMID- 30216389
TI  - Unrecognized myocardial infarction detected on cardiac magnetic resonance
      imaging: Association with coronary artery calcium score and cardiovascular risk
      prediction scores in asymptomatic Asian cohort.
AB  - BACKGROUND: To investigate the association between unrecognized myocardial
      infarction (UMI) assessed with cardiac magnetic resonance (CMR) and coronary
      artery calcium (CAC) and cardiovascular risk prediction scores in asymptomatic
      Asian subjects. MATERIALS AND METHODS: Total 872 asymptomatic subjects without
      prior cardiovascular event (male:female, 817:55; age, 53.88 +/- 5.91) who
      underwent both CMR and CAC scoring CT were included. UMI were accessed and
      framingham risk score (FRS) and ASCVD (atherosclerotic cardiovascular disease)
      risk score by ACC/AHA were calculated. RESULTS: Late gadolinium enhancement
      indicating UMI was noted in 23 of 872 subjects (2.64%), but only three of them
      showed ECG abnormality (13.04%). Subjects with UMI showed higher CAC scores, FRS,
      and ASCVD scores than those without UMI (p < .001, p = .011 and p = .024,
      respectively). The prevalence of UMI differed significantly according to the CAC
      scores as follows: 1% in CAC = 0 (4/403), 1% in 1 <= CAC <100 (2/293), 6.1% in
      100 <= CAC < 400 (7/114) and 14.5% in CAC >= 400 (9/62), respectively (p < .001).
      Receiver operating characteristics (ROC) analysis by using CAC score demonstrated
      an area under the curve (AUC) of 0.816 (95% confidence interval (CI), 0.780
      0.848; p < .0001) for predicting UMI, which is superior to FRS [AUC, 0.712; 95%
      CI, 0.671-0.751; p = .009] and ASCVD risk score [AUC, 0.689; 95% CI, 0.648-0.729;
      p = .036]. CONCLUSION: The prevalence of UMI increases with increasing burden of
      CAC and FRS. CAC score is a good discriminator for UMI, superior to FRS and ASCVD
      score, in asymptomatic population.

PMID- 30216388
TI  - Assessment of the lethal and sublethal effects by spinetoram on cotton bollworm.
AB  - Helicoverpa armigera is an universal pest around the world, which has recovered
      again in recent years because of the adjustment of cropping structure and
      resistance to Bacillus thuringiensis (Bt) in China. As a new insecticide
      spinetoram is extensively used to control many pest insects, including H.
      armigera. However the lethal and sublethal effects of spinetoram on cotton
      bollworm have not been assessed. In the present study, the toxicity of spinetoram
      against cotton bollworm was tested under laboratory conditions. Results
      demonstrated spinetoram showed an excellent activity against H. armigera,
      especially, against Bt (Cry1Ac) resistant H. armigera. Treatment with spinetoram
      at the doses of 0.19 mg/kg and 0.36 mg/kg (LC8 and LC20 after 24h oral exposure)
      significantly arrested the development of surviving larvae and caused significant
      decrease in larvae wet weight. Besides, the survivors after spinetoram treatments
      showed significant reduction of pupation ratio, pupal weight, emergence ratio,
      longevity and fecundity of adults. At same time, spinetoram treatments resulted
      in significant increase in the prepupal and pupal periods of survivors. In
      summary, these results showed that spinetoram could be used as an effective
      pesticide to control H. armigera, especially Cry1Ac-ressitacne, consequently to
      take both lethal and sublethal effects to cotton bollworm into consideration in
      cotton bollworm control strategy.

PMID- 30216392
TI  - 4 pearls for treating musculoskeletal pain.

PMID- 30216390
TI  - Feasibility of school-based health education intervention to improve the
      compliance to mass drug administration for lymphatic Filariasis in Lalitpur
      district, Nepal: A mixed methods among students, teachers and health program
      manager.
AB  - BACKGROUND: Ensuring reduction in transmission of lymphatic Filariasis (LF) and
      addressing the compliance of people to mass drug administration (MDA) has led to
      renewed efforts in the field. School-based health education (SBHE) intervention,
      considered a cost-effective strategy with potential to reach the wider public
      through young people, was adopted as a strategy for social mobilization. This
      study assessed SBHE perceptions, implementation barriers, and factors in the
      supporting environment as well as its efficiency to successfully change LF MDA
      related knowledge and practice. METHODS: This mixed methods study was conducted
      in four sites of Lalitpur district, Nepal. Classroom-based interactive health
      education sessions were used as the main intervention strategy in the study. In
      total, 572 students were assigned to intervention and control groups.
      Questionnaires were distributed before and after the intervention. Mann-Whitney
      and McNemar tests were used for analysis. Focus-group discussions with teachers
      and students and in-depth interviews with the district LF program manager as well
      as Education Office and school management authorities were conducted. Qualitative
      thematic analysis approach was adopted. RESULTS: Intervention curriculum played a
      significant role in increasing children's knowledge and practice (p<0.001).
      Barriers for school-based interventions were budget constraints, human resource
      deficiencies, lack of opportunities to conduct practical classes under the
      curriculum, and lack of collaboration with parents. Supportive factors were
      training provision, monitoring and evaluation practice, adequate facilities and
      equipment, positive parental attitudes, presence of interested teachers and
      students, and prioritization by program implementers. CONCLUSION: Effective
      program planning practices such as proper fiscal management, human resource
      management, training mechanisms, and efforts to promote practical classes and
      coordination with parents are required to develop and institutionalize the
      intervention. Effective learning and a supportive school environment appear to be
      important components to support implementation. The SBHE intervention is a
      feasible and promising intervention for accelerating compliance towards MDA to
      eliminate LF.

PMID- 30216391
TI  - Correction: Limited Clinical Utility of Remote Ischemic Conditioning in Renal
      Transplantation: A Meta-Analysis of Randomized Controlled Trials.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0170729.].

PMID- 30216393
TI  - Buprenorphine to treat opioid use disorder: A practical guide.
AB  - Medication-assisted treatment is demonstrably superior to abstinence and
      counseling in maintaining sobriety. The authors examine this effective agent.

PMID- 30216394
TI  - Consider these exercises for chronic musculoskeletal conditions.
AB  - Exercise interventions reduce pain and improve function in knee/hip OA, chronic
      low back pain, shoulder pain, Achilles tendinopathy, and lateral epicondylitis.

PMID- 30216395
TI  - CDC recommendations for the 2018-2019 influenza season.
AB  - Vaccines will contain a new A (H3N2) component and B antigen. The live attenuated
      influenza vaccine returns as an option for those 2- to 49-years of age.

PMID- 30216396
TI  - 24-year-old with history of smoking tobacco and cannabis . dyspnea . chest
      tightness.

PMID- 30216397
TI  - PURL: Time to stop glucosamine and chondroitin for knee OA?
AB  - Prior studies provided conflicting results regarding the efficacy of these
      medications. This study offers evidence for discontinuing them.

PMID- 30216398
TI  - Photo Rounds: Painful facial blisters, fever, and conjunctivitis.
AB  - Following Tx for facial blisters, our patient returned with what appeared to be
      viral conjunctivitis. Further evaluation revealed a missed tip-off to the proper
      Dx.

PMID- 30216399
TI  - How often does long-term PPI therapy cause clinically significant hypomagnesemia?

PMID- 30216400
TI  - Do statins alter the risk or progression of dementia?

PMID- 30216401
TI  - Photo Rounds: Rapid-onset rash in child.
AB  - Our patient's pruritic rash was spreading throughout his trunk and arms. An acute
      infection 10 days earlier shed light on the diagnosis.

PMID- 30216402
TI  - CV risk prediction tools: Imperfect, Yes, but are they serviceable?
AB  - CVD risk prediction tools have largely been used to determine the advisability of
      statin therapy. They might be better used to counsel patients about across-the
      board risk factor modification.

PMID- 30216403
TI  - Family Medicine Ethics: An Integrative Approach.
AB  - The practice of modern medical ethics is largely acute, episodic, fragmented,
      problem-focused, and institution-centered. Family medicine, in contrast, is built
      upon a relationship-based model of care that is accessible, comprehensive,
      continuous, contextual, community-focused and patient-centered. "Doing ethics" in
      the day-to-day practice of family medicine is therefore different from doing
      ethics in many other fields of medicine, emphasizing different strengths and
      exemplifying different values. For family physicians, medical ethics is more than
      just problem solving. It requires reconciling ethical concepts with modern
      medicine and asking the principal medical ethics question-What, all things
      considered, should happen in this situation?-at every clinical encounter over the
      course of the patient-doctor relationship. We assert that family medicine ethics
      is an integral part of family physicians' day-to-day practice. We frame this
      approach with a four-step process modified from other ethical decision-making
      models: (1) Identify situational issues; (2) Identify involved stakeholders; (3)
      Gather objective and subjective data; and (4) Analyze issues and data to direct
      action and guide behavior. Next, we review several ethical theories commonly used
      for step four, highlighting the process of wide reflective equilibrium as a key
      integrative concept in family medicine. Finally, we suggest how to incorporate
      family medicine ethics in medical education and invite others to explore its use
      in teaching and practice.

PMID- 30216404
TI  - Factors influencing pain and efficacy of topical photodynamic therapy: a
      retrospective study.

PMID- 30216405
TI  - Infrared spectroscopy as a novel tool to diagnose onychomycosis.
AB  - BACKGROUND: The determination of causative organisms of onychomycosis is still
      not optimal. There remains a need for a cheap, fast and easy-to-perform
      diagnostic tool with a high capacity to distinguish between organisms.
      OBJECTIVES: To determine whether attenuated total-reflectance Fourier transform
      infrared (ATR-FTIR) spectroscopy can detect and differentiate causative agents in
      culture-based, ex vivo nail and in vivo nail models. METHODS: A methodological
      study was conducted. Both the ex vivo nail model and in vivo pilot study were
      carried out in an academic university hospital. RESULTS: Analysis of cultured
      fungi revealed spectral differences for dermatophytes (1692-1606 and 1044-1004 cm
      1 ) and nondermatophytes and yeasts (973-937 cm-1 ), confirmed by dendrograms
      showing an excellent separation between samples from different genera or species.
      Exploration of dermatophytes, nondermatophytes and yeasts growing on ex vivo
      nails exposed prominent differences from 1200 to 900 cm-1 . Prediction models
      resulted in a 96.9% accurate classification of uninfected nails and nails
      infected with dermatophytes, nondermatophytes and yeasts. Overall correct
      classification rates of 91.0%, 97.7% and 98.6% were obtained for discrimination
      between dermatophyte, nondermatophyte and yeast genera or species, respectively.
      Spectra of in vivo infected and uninfected nails also revealed distinct spectral
      differences (3000-2811 cm-1 , 1043-950 cm-1 and 1676-1553 cm-1 ), illustrated by
      two main clusters (uninfected vs. infected) on a dendrogram. CONCLUSIONS: Our
      data suggest that ATR-FTIR spectroscopy may be a promising, fast and accurate
      method to determine onychomycosis, including identification of the causative
      organism, bypassing the need for lengthy fungal cultures.

PMID- 30216407
TI  - RMI and ROMA are equally effective in discriminating between benign and malignant
      gynecological tumors: A prospective population-based study.
AB  - INTRODUCTION: Our primary objective was to test the hypothesis that human
      epididymal protein 4 (HE4) and risk of ovarian malignancy index outperform the CA
      125 and risk of malignancy index tests in categorizing a pelvic mass into high or
      low risk of malignancy in a Swedish population. Furthermore, cut-off values
      needed to be defined for HE4 and ROMA in premenopausal and postmenopausal women
      prior to their introduction to clinical practice. A third objective was to
      investigate the correlation between HE4 levels in serum and urine. MATERIAL AND
      METHODS: Women with a pelvic mass scheduled for surgery were recruited from nine
      hospitals in south-east Sweden. Preoperative blood samples were taken for
      analyzing CA125 and HE4 as well as urine samples for analyzing HE4. RESULTS: We
      enrolled a total of 901 women, of whom 784 were evaluable. In the premenopausal
      and postmenopausal groups, no significant differences were found for sensitivity,
      positive and negative predictive value, either for RMI versus ROMA or for CA125
      versus HE4 using a fixed specificity of 75%. Cut-off values indicating malignancy
      were established for HE4 and ROMA in premenopausal and postmenopausal women. We
      found no correlation between HE4 concentration in serum and urine. CONCLUSIONS:
      We could not confirm that ROMA had diagnostic superiority over RMI in
      categorizing women with a pelvic mass into low-risk or high-risk groups for
      malignancy in a Swedish population. We have defined cut-off values for HE4 and
      ROMA. The lack of correlation between serum and urine HE4 obviates the
      introduction of urine HE4 analysis in clinical diagnostics.

PMID- 30216406
TI  - Management of congenital ichthyoses: European guidelines of care, part one.
AB  - These guidelines for the management of congenital ichthyoses have been developed
      by a multidisciplinary group of European experts following a systematic review of
      the current literature, an expert conference held in Toulouse in 2016 and a
      consensus on the discussions. They summarize evidence and expert-based
      recommendations and are intended to help clinicians with the management of these
      rare and often complex diseases. These guidelines comprise two sections. This is
      part one, covering topical therapies, systemic therapies, psychosocial
      management, communicating the diagnosis and genetic counselling.

PMID- 30216408
TI  - Breaking the rules: Phylogeny, not life history, explains dental eruption
      sequence in primates.
AB  - OBJECTIVES: Although a great deal is known about the biology of tooth development
      and eruption, there remains disagreement about the factors driving the evolution
      of dental eruption sequence. We assessed postcanine eruption sequence across a
      large sample of primates to test two hypotheses: (1) Dental eruption sequence is
      significantly correlated with life history and body size variables that capture
      postnatal growth and longevity (Schultz's Rule), and (2) Dental eruption sequence
      is conserved phylogenetically. MATERIALS AND METHODS: We assessed postcanine
      dental eruption sequence for 194 individuals representing 21 primate genera
      spanning eight families. With the inclusion of an additional 29 primate genera
      from the literature, this is the most comprehensive report on dental eruption
      sequence in primates to date. We used a series of phylogenetic analyses to
      statistically compare dental eruption sequence to life history and body size and
      test for phylogenetic signal in these traits. RESULTS: Dental eruption sequence
      is conserved phylogenetically in primates, and body and brain size are both
      significantly associated with dental eruption sequence. Ancestral state
      reconstruction supports the hypothesis that the third molar erupted before one or
      more of the premolars in the ancestor of primates and derived clades within
      primates evolved an eruption sequence in which the third molar erupts after the
      premolars. DISCUSSION: Schultz's Rule, as it is currently written and applied, is
      not supported by this extended data set. Our results demonstrate that dental
      eruption sequence is a far better predictor of phylogeny and will likely prove
      useful in phylogenetic hypotheses about relationships between extinct and extant
      mammalian taxa. The evolution of dental eruption sequence is likely driven by
      factors that significantly influence body size and mandibular symphyseal fusion.

PMID- 30216409
TI  - Shifts in pollen release envelope differ between genera with non-uniform climate
      change.
AB  - PREMISE OF THE STUDY: Plant phenological responses to climate change now
      constitute one of the best studied areas of the ecological impacts of climate
      change. Flowering time responses to climate change of wind-pollinated species
      have, however, been less well studied. A novel source of flowering time data for
      wind-pollinated species is allergen monitoring records. METHODS: We studied the
      male flowering time response to climatic variables of two wind-pollinated genera,
      Betula (Betulaceae) and Populus (Salicaceae), using pollen count records over a
      17-year period. KEY RESULTS: We found that changes in the pollen release envelope
      differed between the two genera. Over the study period, the only month with a
      significant rise in temperature was April, resulting in the duration of pollen
      release of the April-flowering Populus to shorten and the start and peak of the
      May-flowering Betula to advance. The quantity of pollen released by Betula has
      increased and was related to increases in the previous year's August
      precipitation, while the quantity of pollen released by Populus has not changed
      and was related to the previous year's summer and autumn temperatures.
      CONCLUSIONS: Our findings suggest that taxa differ in the reproductive
      consequences of environmental change. Differing shifts in phenology among species
      may be related to different rates of change in climatic variables in different
      months of the year. While our study only considers two genera, the results
      underscore the importance of understanding non-uniform intra-annual variation in
      climate when studying the ecological implications of climate change.

PMID- 30216410
TI  - Similarities and differences in intrapopulation trait correlations of co
      occurring tree species: consistent water-use relationships amid widely different
      correlation patterns.
AB  - PREMISE OF THE STUDY: General relationships among functional traits have been
      identified across species, but the forces shaping these relationships remain
      largely unknown. Adopting an approach from evolutionary biology, we studied
      similarities and differences in intrapopulation trait correlations among locally
      co-occurring tree species to assess the roles of constraints, phylogeny, and the
      environmental niche in shaping multivariate phenotypes. We tested the hypotheses
      (1) that intrapopulation correlations among functional traits are largely shaped
      by fundamental trade-offs or constraints and (2) that differences among species
      reflect adaptation to their environmental niches. METHODS: We compared pairwise
      correlations and correlation matrices of 17 key functional traits within and
      among temperate tree species. These traits describe three well-established trade
      off dimensions characterizing interspecific relationships among physiological
      functions: resource acquisition and conservation; sap transport and mechanical
      support; and branch architecture. KEY RESULTS: Six trait pairs are consistently
      correlated within populations. Of these, only one involves dimensionally
      independent traits: LMA-delta13 C. For all other traits, intrapopulation
      functional trait correlations are weak, are species-specific, and differ from
      interspecific correlations. Species intrapopulation correlation matrices are
      related to neither phylogeny nor environmental niche. CONCLUSIONS: The results
      (1) suggest that the functional design of these species is centered on efficient
      water use, (2) highlight flexibility in plant functional design across species,
      and (3) suggest that intrapopulation, local interspecific, and global
      interspecific correlations are shaped by processes acting at each of these
      scales.

PMID- 30216411
TI  - Cancer is not a risk factor for bullous pemphigoid: 10-year population-based
      cohort study.
AB  - BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune bullous
      disease. Whether there is an increased risk for subsequent BP among patients with
      cancer is still unclear. OBJECTIVES: To evaluate the risk for subsequent BP in
      patients with cancer. METHODS: This nationwide population-based cohort study was
      based on data obtained from the Taiwan National Health Insurance Database between
      2000 and 2011. A total of 36 838 patients with cancer and 147 352 age-, sex- and
      index-date-matched controls were recruited. The hazard ratio (HR) of subsequent
      BP in the patients with cancer was analysed using a Fine-Gray competing risk
      regression model with mortality as the competing event. RESULTS: The incidence of
      BP per 100 000 person-years was 17.2 in the patients with cancer and 19.8 in the
      controls; therefore, the crude incidence rate ratio was 0.87 [95% confidence
      interval (CI) 0.53-1.36]. The HR of subsequent BP in the patients with cancer was
      0.47 (95% CI 0.23-0.94) using the Fine-Gray competing risk regression model. Age
      (HR 1.05, 95% CI 1.03-1.07), diabetes mellitus (HR 1.69, 95% CI 1.10-2.59) and
      cerebrovascular disease (HR 2.14, 95% CI 1.36-3.34) were independent risk factors
      for BP. CONCLUSIONS: The incidence of BP in patients with cancer was not higher
      than in the control group. Cancer is not a risk factor for BP.

PMID- 30216412
TI  - A sensitive and specific assay for the serological diagnosis of antilaminin 332
      mucous membrane pemphigoid.
AB  - BACKGROUND: Antilaminin 332 mucous membrane pemphigoid (MMP) is an autoimmune
      subepidermal blistering disease with predominant mucosal involvement and
      autoantibodies against laminin 332. Malignancies have been associated with this
      disease; however, no standardized detection system for antilaminin 332 serum
      antibodies is widely available. OBJECTIVES: Development of a sensitive and
      specific assay for the detection of antilaminin 332 antibodies. METHODS: An
      indirect immunofluorescence (IF) assay using recombinant laminin 332 was
      developed and probed with a large number of antilaminin 332 MMP patient sera (n =
      93), as well as sera from patients with antilaminin 332-negative MMP (n = 153),
      bullous pemphigoid (n = 20), pemphigus vulgaris (n = 20) and noninflammatory
      dermatoses (n = 22), and healthy blood donors (n = 100). RESULTS: In the novel IF
      assay, sensitivities with the laminin 332 heterotrimer and the individual alpha3,
      beta3 and gamma2 chains were 77%, 43%, 41% and 13%, respectively, with
      specificities of 100% for each substrate. The sensitivity for the heterotrimer
      increased when an anti-IgG4 enriched antitotal IgG conjugate was applied.
      Antilaminin 332 reactivity paralleled disease activity and was associated with
      malignancies in 25% of patients with antilaminin 332 MMP. CONCLUSIONS: The novel
      IF-based assay will facilitate the serological diagnosis of antilaminin 332 MMP
      and may help to identify patients at risk of a malignancy.

PMID- 30216413
TI  - MELAS: Monitoring treatment with magnetic resonance spectroscopy.
AB  - BACKGROUND: To assess the utility of Magnetic Resonance Spectroscopy (MRS) as a
      biomarker of response to L-arginine in mitochondrial encephalomyopathy with
      lactic acidosis and stroke-like episodes (MELAS). AIMS: To describe a case of
      MELAS treated with L-arginine that showed improvement clinically and on serial
      MRS METHODS: MRS was performed on a 1.5-Tesla scanner to evaluate a MELAS patient
      before, during, and after intravenous (IV) L-arginine therapy for the treatment
      of stroke-like episodes. L-arginine was infused at a dose of 500 mg/kg daily for
      7 days followed by oral arginine therapy. RESULTS: The patient had clinical
      improvement after treatment with IV L-arginine. MRS performed before, during, and
      after treatment with IV L-arginine showed significant improvement in brain
      lactate and increase in the N-acetylaspartate/Choline (NAA/Cho) ratio compared to
      pre-treatment baseline. CONCLUSION: Serial MRS imaging showed significant
      improvement in lactate peaks and NAA/Cho ratios that corresponded with clinical
      improvement after L-arginine therapy. Given this correlation between radiologic
      and clinical improvement, MRS may be a useful biomarker assessing response to
      treatment in MELAS.

PMID- 30216414
TI  - Prophylactic treatment against GM-CSF, but not IL-17, abolishes relapses in a
      chronic murine model of multiple sclerosis.
AB  - The pathogenic role of IL-17 and GM-CSF has been unravelled in experimental
      autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS).
      However, in most models, EAE is characterised by a monophasic attack which is not
      representative of the relapsing nature nor the chronicity displayed in MS. Here,
      we used proteolipid protein peptide (PLP139-151 ) to trigger EAE-relapses (EAE
      II) in SJL mice that had recovered from a primary-EAE episode (EAE-I). This
      procedure resulted in severe and irreversible disease that, unlike EAE-I, was not
      abolished by anti-IL-17-mAb. In contrast, prophylactic anti-GM-CSF-mAb treatment
      prevented EAE-I and -II. Strikingly, the expression of T-cell transcription
      factors and cytokines/chemokines in mice treated with anti-GM-CSF during both EAE
      episodes was silenced. Anti-GM-CSF-mAb treatment administered only during EAE-II
      did not completely prevent relapses but mice ultimately reached full recovery.
      Anti-GM-CSF treatment also strongly impaired and ultimately resolved monophasic
      MOG35-55 -induced EAE in C57Bl/6 mice. In such protected mice, anti-GM-CSF
      treatment also prevented a further relapse induced by MOG-revaccination. These
      results underscore the critical role of GM-CSF on pro-inflammatory mediator
      production. Furthermore, we observed a strong preventive and curative effect of
      anti-GM-CSF neutralisation in two EAE models, relapsing and chronic. Altogether
      these findings are relevant for further MS research.

PMID- 30216415
TI  - "Like heart valve clinic, it probably saves lives, but... Who has time for that?"
      The challenge of disseminating multidisciplinary cancer care in the United
      States.

PMID- 30216417
TI  - Disease site as a prognostic factor for mycosis fungoides: an analysis of 2428
      cases from the US National Cancer Database.

PMID- 30216416
TI  - The relationship between household income and patient-reported symptom distress
      and quality of life in children with advanced cancer: A report from the PediQUEST
      study.
AB  - BACKGROUND: Children with advanced cancer experience high symptom distress, which
      negatively impacts their health-related quality of life (HRQOL). To the authors'
      knowledge, the relationship between income and symptom distress and HRQOL is not
      well described. METHODS: The Pediatric Quality of Life and Symptoms Technology
      (PediQUEST) multisite clinical trial evaluated an electronic patient-reported
      outcome system to describe symptom distress and HRQOL in children with advanced
      cancer via repeated surveys. The authors performed a secondary analysis of
      PediQUEST data for those children with available parent-reported household income
      (dichotomized at 200% of the Federal Poverty Level and categorized as low income
      [<$50,000/year] or high income [>=$50,000/year]). The prevalence of the 5 most
      commonly reported physical and psychological symptoms was compared between
      groups. Multivariable generalized estimating equation models were used to test
      the association between household income and symptom distress and HRQOL. RESULTS:
      A total of 78 children were included in the analyses: 56 (72%) in the high-income
      group and 22 (28%) in the low-income group. Low-income children were more likely
      to report pain than high-income children (64% vs 42%; P=.02). In multivariable
      models, children from low-income families demonstrated a uniform trend toward
      higher total (betalow-high =3.1; 95% confidence interval [95% CI], -0.08 to 6.2
      [P=.06]), physical (beta=3.8; 95% CI, -0.4 to 8.0 [P=.09]), and psychological
      (beta=3.46; 95% CI, -1.91 to 8.84 [P=.21]) symptom distress compared with
      children from high-income families. Low income was associated with a uniform
      trend toward lower total (beta=-7.9; 95% CI, -14.8, to -1.1 [P=.03]), physical
      (beta=-11.2; 95% CI, -21.2 to -1.2 [P=.04]), emotional (beta=-5.8; 95% CI, -13.6
      to 2.0 [P=.15]), social (beta=-2.52; 95% CI, -9.27 to 4.24 [P=.47]), and school
      (beta=-9.8; 95% CI, -17.8 to -1.8 [P=.03]) HRQOL. CONCLUSIONS: In this cohort of
      children with advanced cancer, children from low-income families were found to
      experience higher symptom burden and worse QOL.

PMID- 30216419
TI  - The utility of optical coherence tomography for diagnosis of basal cell
      carcinoma: a quantitative review.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a noninvasive near-infrared
      light imaging technology that can be utilized to diagnose basal cell carcinomas
      (BCCs) based on specific morphological features. OBJECTIVES: To conduct a
      quantitative review using tumour-level data from published studies to assess: (i)
      the in vivo diagnostic accuracy of different OCT systems; (ii) correlation
      between OCT features and histopathological diagnosis; and (iii) factors that
      impact the accuracy of tumour depth estimation. METHODS: Primary tumour-level
      data were extracted from published studies on the use of time-domain (TD-OCT),
      frequency-domain (FD-OCT) and high-definition (HD-OCT) systems for diagnosis of
      BCCs. Quality assessment was performed using the Newcastle-Ottawa Scale and the
      Cochrane Risk of Bias Tool. Sensitivity and specificity for diagnosis of BCC,
      prevalence of morphological features and correlation of tumour depth between OCT
      and histopathology were analysed. RESULTS: In total, 901 BCCs from 31 studies
      were included. The sensitivity and specificity were 89.3% and 60.3% overall, and
      were highest for FD-OCT (93.7% and 61.4%, respectively). The most prevalent
      morphological features were lobular pattern (80.2%, 315 of 393 tumours) and hyper
      reflective peritumoral stroma (51.7%, 203 of 393). Concordance between OCT and
      histopathological tumour depth categories was moderate (Pearson coefficient
      0.48); it was highest for tumours < 1 mm and those on the extremities. The
      overall bias was 0.075 mm with an agreement range from -0.88 to 1.03 mm. HD-OCT
      and FD-OCT were superior to TD-OCT at identifying morphological features, but not
      at tumour depth estimation. CONCLUSIONS: OCT is a viable tool for in vivo
      diagnosis of BCCs. FD-OCT and HD-OCT outperformed TD-OCT in diagnostic accuracy
      and detection of morphological features, but not tumour depth estimation.

PMID- 30216418
TI  - Imatinib and everolimus in patients with progressing advanced chordoma: A phase 2
      clinical study.
AB  - BACKGROUND: We present the results of an academic phase 2 study on imatinib plus
      everolimus in patients who have progressive advanced chordoma. METHODS: In
      January 2011, 43 adult chordoma patients were enrolled in the study and received
      imatinib 400 mg/day and everolimus 2.5 mg/day until progression or limiting
      toxicity. Eligible patients had progressed in the 6 months before study entry.
      PDGFRB, S6, and 4EBP1 expression and phosphorylation were evaluated by way of
      immunohistochemistry and/or western blotting. The primary endpoint was the
      overall response rate (ORR) according to Choi criteria. Secondary endpoints were
      RECIST 1.1 response, progression-free survival (PFS), overall survival (OS),
      correlation between S6/4EBP1 phosphorylation and response. RESULTS: Thirteen of
      43 patients were pretreated with imatinib. Among 40 of the 43 patients who were
      evaluable by Choi criteria, the best responses were 9 with partial response (ORR,
      20.9%), 24 with stable disease (SD) (ORR, 55.8%), and 7 with progressive disease
      (ORR, 16.3%). Forty-two patients were evaluable by RECIST criteria, with 1
      partial response (ORR, 2.3%), 37 stable disease (ORR, 86%), and 4 progressive
      disease (ORR, 9.3%). The median PFS according to Choi criteria was 11.5 months
      (range, 4.6-17.6 months), and 58.8% and 48.1% of patients were progression-free
      at 9 and 12 months, respectively. The median PFS by RECIST criteria was 14
      months; the median OS was 47.1 months. When assessable, S6/4EBP1 was
      phosphorylated in a high and moderate/low proportion of tumor cells in responsive
      and nonresponsive patients, respectively. Toxicity caused a temporary and
      definitive treatment discontinuation in 60.5% and 30.2% of patients,
      respectively. CONCLUSIONS: Imatinib plus everolimus showed a limited activity in
      progressing advanced chordoma. Interestingly, the amount of tumor cells activated
      for mammalian target of rapamycin effectors correlated with the response.
      Toxicity was not negligible.

PMID- 30216420
TI  - Subglottic airway injury caused by difficult tracheal tube passage.

PMID- 30216421
TI  - Electrical interference using an Eschmann T-Series operating table.

PMID- 30216422
TI  - Ilio-inguinal-transversus abdominis plane (I-TAP) nerve block for elective
      caesarean section. A reply.

PMID- 30216423
TI  - Non-invasive blood pressure measurement displays - a reply.

PMID- 30216424
TI  - Topical benzydamine for preventing postoperative sore throat. A reply.

PMID- 30216426
TI  - Bougie vs. guidewire for tracheal intubation.

PMID- 30216425
TI  - Subglottic airway injury caused by difficult tracheal tube passage. A reply.

PMID- 30216427
TI  - Non-invasive blood pressure measurement displays.

PMID- 30216428
TI  - Topical benzydamine for preventing postoperative sore throat.

PMID- 30216429
TI  - Ilio-inguinal-transversus abdominis plane (I-TAP) nerve block for elective
      caesarean section.

PMID- 30216430
TI  - How becoming a mother shapes implicit and explicit responses to infant cues.
AB  - This study (a) investigates effects of the transition to motherhood on implicit
      and explicit responses to infant cues; (b) assesses influences of prior parenting
      and delivery experiences on implicit and explicit responses to infant cues; and
      (c) investigates relations between implicit and explicit responses to infant cues
      and parenting beliefs. A total of 45 pregnant women were followed from the sixth
      month of pregnancy to the third month after the childbirth and were administered
      a Single Category Implicit Association Test, a semantic differential scale, the
      Adult Parental Acceptance-Rejection scale, and the Parental Style Questionnaire.
      The transition to motherhood influenced explicit not implicit responses; only
      implicit responses were shaped by prior parenting experiences and mode of
      delivery; and parenting beliefs were related in independent and different ways to
      implicit and explicit evaluations. These findings indicate that implicit
      responses are valid and meaningful indices of maternal responsiveness to infants.

PMID- 30216432
TI  - Statins influence epithelial expression of the anti-microbial peptide LL-37/hCAP
      18 independently of the mevalonate pathway.
AB  - Anti-microbial resistance increases among bacterial pathogens and new therapeutic
      avenues needs to be explored. Boosting innate immune mechanisms could be one
      attractive alternative in the defence against infectious diseases. The
      cholesterol-lowering drugs, statins, have been demonstrated to also affect the
      immune system. Here we investigate the effect of statins on the expression of the
      human cathelicidin anti-microbial peptide (CAMP) LL-37/hCAP-18 [encoded by the
      CAMP gene] and explore the underlying mechanisms in four epithelial cell lines of
      different origin. Simvastatin induced CAMP expression in bladder epithelial cells
      telomerase-immortalized uroepithelial cells (TERT-NHUCs), intestinal cells HT-29
      and keratinocytes HEKa, but not in airway epithelial cells A549. Gene induction
      in HEKa cells was reversible by mevalonate, while this effect was independent of
      the cholesterol biosynthesis pathway in TERT-NHUCs. Instead, inhibition of
      histone deacetylases by simvastatin seems to be involved. For HT-29 cells, both
      mechanisms may contribute. In addition, simvastatin increased transcription of
      the vitamin D-activating enzyme CYP27B1 which, in turn, may activate LL-37/hCAP
      18 production. Taken together, simvastatin is able to promote the expression of
      LL-37/hCAP-18, but cell line-specific differences in efficacy and the involved
      signalling pathways exist.

PMID- 30216433
TI  - The Earlier the Better? Individual Participant Data and Traditional Meta-analysis
      of Age Effects of Parenting Interventions.
AB  - Strong arguments have been made for early intervention for child problems,
      stating that early is more effective than later, as the brain is more malleable,
      and costs are lower. However, there is scant evidence from trials to support this
      hypothesis, which we therefore tested in two well-powered, state-of-the-art meta
      analyses with complementary strengths: (a) Individual participant data (IPD) meta
      analysis of European trials of Incredible Years parenting intervention (k = 13, n
      = 1696; age = 2-11); (b) Larger, trial-level robust variance estimation meta
      analysis of a wider range of parenting programs (k = 156, n = 13,378, Mage  = 2
      10) for reducing disruptive behavior. Both analyses found no evidence that
      intervention earlier in childhood was more effective; programs targeted at a
      narrower age range were no more effective than general ones.

PMID- 30216431
TI  - Identification of circular RNAs hsa_circ_0044235 in peripheral blood as novel
      biomarkers for rheumatoid arthritis.
AB  - Circular RNAs (circRNAs) are a new class of RNAs that can be used as biomarkers
      in clinical blood samples. However, little is known about circRNAs' diagnostic
      values for rheumatoid arthritis (RA). In this study, the hsa_circ_0054189,
      hsa_circ_0008675, hsa_circ_0082689, hsa_circ_0082688, hsa_circ_0010932,
      hsa_circ_0002473 and hsa_circ_0044235 in peripheral blood were determined by
      quantitative reverse transcription-polymerase chain reaction (qRT-PCR). For
      hsa_circ_0044235, only one abnormal expression circRNAs in peripheral blood was
      selected as a targeted circRNA to explore the diagnostic value for RA. Our work
      demonstrated that the hsa_circ_0044235 in peripheral blood was decreased
      significantly in RA patients. The hsa_circ_0044235 in peripheral blood from RA
      patients did not correlate with C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), rheumatoid factor (RF), anti-citrullinated protein
      antibodies (ACPA) or disease activity score 28 (DAS28). Receiver operating
      characteristic (ROC) curve analysis suggested that the hsa_circ_0044235 in
      peripheral blood has significant value in the diagnosis of RA. The risk score
      based on hsa_circ_0044235 in peripheral blood also distinguished significantly
      the patients with RA from systemic lupus erythematosus (SLE). This study suggests
      that the hsa_circ_0044235 in peripheral blood may be a potential biomarker of
      patients with RA.

PMID- 30216434
TI  - Clinical and laboratory features of seventy-eight UK patients with Good's
      syndrome (thymoma and hypogammaglobulinaemia).
AB  - Good's syndrome (thymoma and hypogammaglobulinaemia) is a rare secondary
      immunodeficiency disease, previously reported in the published literature as
      mainly individual cases or small case series. We use the national UK-Primary
      Immune Deficiency (UKPID) registry to identify a large cohort of patients in the
      UK with this PID to review its clinical course, natural history and prognosis.
      Clinical information, laboratory data, treatment and outcome were collated and
      analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were
      female, were reviewed. Median age of presentation was 54 years. Absolute B cell
      numbers and serum immunoglobulins were very low in all patients and all received
      immunoglobulin replacement therapy. All patients had undergone thymectomy and
      nine (12%) had thymic carcinoma (four locally invasive and five had disseminated
      disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T cells were
      significantly lower in these patients with malignant thymoma. Seventy-four (95%)
      presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic
      sinusitis, but only eight (10%) had serious invasive fungal or viral infections.
      Patients with AB-type thymomas were more likely to have bronchiectasis. Twenty
      (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism,
      arthritis, myasthenia gravis, systemic lupus erythematosus, Sjogren's syndrome).
      There was no association between thymoma type and autoimmunity. Seven (9%)
      patients had died. Good's syndrome is associated with significant morbidity
      relating to infectious and autoimmune complications. Prospective studies are
      required to understand why some patients with thymoma develop persistent
      hypogammaglobulinaemia.

PMID- 30216435
TI  - Incidence of squamous cell carcinoma in oral lichen planus: a 25-year population
      based study.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory condition of the
      oral mucosa. Multiple studies have shown that approximately 1% of patients with
      OLP will develop oral squamous cell carcinoma (OSCC), however, no study has taken
      a population-based multicenter approach to demonstrate this association. Our main
      objective was to determine the incidence of OSCC in OLP in a specific population
      and secondarily to assist physicians regarding appropriate long-term monitoring
      of patients with OLP. METHODS: We conducted a population-based retrospective
      cohort study. Patients with OLP from 1986 through 2010 were identified using the
      Rochester Epidemiology Project (REP) for Olmsted County, Minnesota. For each OLP
      case (n = 303), we randomly selected two age- and gender-matched referents (n =
      606). OLP diagnosis was established based on the World Health Organization (WHO)
      criteria. Medical records were reviewed for development of OSCCafter the OLP
      diagnosis (index date). The association between OLP and development of OSCC was
      assessed. RESULTS: In total, 303 patients with incident OLP were identified; the
      overall incidence of OLP per 100,000 person-years was 11.4 (95% CI, 10.1-12.7).
      Among the OLP cohort, 7 had OSCC (incidence of OSCC, 3.1%; 95% CI, 0.6-6.4%) at
      20 years after OLP diagnosis. Three OSCC cases were identified among the
      referents. Patients with OLP were 4.8 times more likely to have OSCC than the
      matched referents. The median time to OSCC development was 14.7 years earlier for
      the OLP cohort. CONCLUSIONS: Patients with OLP, particularly the erosive type,
      have an increased incidence of OSCC development and should be monitored closely.

PMID- 30216437
TI  - Therapeutic agency, in-session behavior, and patient-therapist interaction.
AB  - OBJECTIVE: The aim of this study was to investigate associations between
      patients' subjective agency, their observable in-session behavior, and the
      patient-therapist interaction during the early phase of psychotherapy. METHODS:
      The sample included 52 depressed patients in psychodynamic psychotherapy. After
      Session 5, the patients' agency and the quality of the therapeutic alliance were
      assessed. Based on session recordings, two independent observers rated the
      patients' involvement, their interpersonal behavior, and the therapists'
      directiveness. RESULTS: Higher agency was associated with stronger therapeutic
      alliances. Patients who indicated higher agency in their therapy participated
      more actively in the session and showed less hostile impact messages. Patients'
      agency was not related to therapists' directiveness. CONCLUSIONS: Patients' sense
      of agency in psychotherapy was associated with more active involvement and
      affiliative interaction. The findings support the idea that patients need to feel
      capable of acting within and having an influence on their therapy to benefit from
      it.

PMID- 30216436
TI  - Oncologist volume and outcomes in older adults diagnosed with diffuse large B
      cell lymphoma.
AB  - BACKGROUND: Although provider-level volume is frequently associated with outcomes
      in cancers requiring complex surgeries, whether similar relations exist for
      cancers treated primarily with systemic therapy is unknown. METHODS: Using a
      population-based cohort analysis of older adults diagnosed with diffuse large B
      cell lymphoma (DLBCL) during the years 2004-2011, we evaluated the association
      between oncologist volume and 4 clinical outcomes (receipt of any chemotherapy,
      receipt of an anthracycline-containing or equivalent regimen, early
      hospitalization, and overall survival). Our primary explanatory variable was
      lymphoma treatment volume, defined as the number of patients with newly diagnosed
      lymphoma for which an oncologist initiated therapy during a 12-month look-back
      period from each incident DLBCL case. RESULTS: We identified 8247 Medicare
      beneficiaries who were newly diagnosed with DLBCL. Chemotherapy was administered
      to 6202 (75.2%) beneficiaries, and 71.4% of cytotoxic regimens contained an
      anthracycline. Beneficiaries who were treated by higher-volume oncologists had
      increased odds of receiving chemotherapy (adjusted odds ratio [aOR], 1.45; 95%
      confidence interval [CI], 1.24-1.70; P <.001) and of receiving an anthracycline
      containing regimen (aOR, 1.26; 95% CI, 1.06-1.50; P = .009). Receiving care from
      a higher-volume provider was also associated with decreased hospitalization (aOR,
      0.80; 95% CI, 0.69-0.95; P = .007) and improved survival (adjusted hazard ratio,
      0.85; 95% CI, 0.79-0.92; P < .001). CONCLUSION: In older adults diagnosed with
      DLBCL, receiving care from a provider with more experience treating lymphoma
      patients was associated with receipt of guideline-adherent therapy, reduced
      hospitalizations, and improved survival. Clinical volume may be an important
      factor in providing high-quality cancer care in the modern era.

PMID- 30216439
TI  - Methylene blue offers neuroprotection after intracerebral hemorrhage in rats
      through the PI3K/Akt/GSK3beta signaling pathway.
AB  - Inflammation and apoptosis are two key factors contributing to secondary brain
      injury after intracerebral hemorrhage (ICH). In the present study, we explored
      the neuroprotective role of methylene blue (MB) in ICH rats and studied the
      potential mechanisms involved. Rats were subjected to local injection of
      collagenase IV in the striatum or sham surgery. We observed that MB treatment
      could exert a neuroprotective effect on ICH by promoting neurological scores,
      decreasing the brain water content, alleviating brain-blood barrier disruption,
      and improving the histological damages in the perihematomal areas. Furthermore,
      we demonstrated that the various mechanisms underlying MB's neuroprotective
      effects linked to inhibited apoptosis and inhibited neuroinflammation. In
      addition, wortmannin, a selective inhibitor of phosphoinositide 3-kinase (PI3K),
      could reverse the antiapoptotic and anti-inflammatory effects of MB, which
      suggested that the PI3K-Akt pathway played an important role. In conclusion,
      these data suggested that MB could inhibit apoptosis and ameliorate
      neuroinflammation after ICH, and its neuroprotective effects might be exerted via
      the activation of the PI3K/Akt/GSK3beta pathway.

PMID- 30216438
TI  - LncRNA HOTAIR functions as a competing endogenous RNA to upregulate SIRT1 by
      sponging miR-34a in diabetic cardiomyopathy.
AB  - The HOX transcript antisense RNA (HOTAIR) long noncoding RNA (lncRNA), a highly
      abundant and conserved imprinted gene, has been implicated in many essential
      biological processes and diseases. However, to date, the significance of HOTAIR
      in diabetic cardiomyopathy (DCM) has never been investigated. The current study
      was designed to determine whether DCM can be regulated by HOTAIR and to elucidate
      the related mechanism. In vivo, streptozotocin (STZ) was injected
      intraperitoneally to induce type 1 diabetes in mice. Cardiomyocyte specific
      HOTAIR overexpression was achieved using an adeno-associated virus system 12
      weeks after STZ injection. In vitro, H9c2 were used to explore the potential
      molecular mechanism of HOTAIR in the regulation of high-glucose-induced
      cardiomyocyte injury. Luciferase reporter assay and RNA immunoprecipitation (RIP)
      were performed to explore the relationship between HOTAIR, microRNA-34a (miR
      34a), and Sirtuin 1 (SIRT1). HOTAIR expression was significantly decreased in
      diabetic mice hearts. Knockdown of HOTAIR in high glucose-induced H9c2 resulted
      in increased oxidative injury, inflammation, and apoptosis in vitro.
      Cardiomyocyte-specific overexpression of HOTAIR improved cardiac function,
      decreased oxidative stress and inflammation, and attenuated myocyte death in mice
      treated with STZ. Mechanistically, the expression of SIRT1/forkhead box protein
      O1 was significantly increased in the HOTAIR-overexpressing hearts compared with
      the control hearts treated with STZ. Moreover, we found HOTAIR functioned as a
      molecular sponge of miR-34a in H9c2 and SIRT1 was identified as a target of miR
      34a. Furthermore, the protective effects of HOTAIR on DCM was abolished in SIRT1
      deficiency mice in vivo. HOTAIR protected against DCM via activation of the SIRT1
      expression by sponging miR-34a.

PMID- 30216440
TI  - Regulatory role of microRNA-320a in the proliferation, migration, invasion, and
      apoptosis of trophoblasts and endothelial cells by targeting estrogen-related
      receptor gamma.
AB  - Recently, microRNAs (miRNAs) have been demonstrated to participate in many
      physiological and biological processes, especially by acting as circulating
      biomarkers or modulators in cell differentiation. Therefore, the aim of the
      current study was to clarify whether microRNA-320a (miR-320a) regulates the
      proliferation, migration, invasion, and apoptosis of trophoblasts and endothelial
      cells. In this study, miR-320a mimics and inhibitors were transfected into
      HTR.8/SVneo cells and human umbilical vein endothelial cells (HUVECs) using
      liposomes. Subsequently, the expression of miR-320a and estrogen-related receptor
      gamma (ERRgamma) mRNA was detected by a reverse transcription quantitative
      polymerase chain reaction, whereas the protein expression of ERRgamma, vascular
      endothelial growth factor (VEGF), angiogenin 1 (Ang-1), human 3beta
      hydroxysteroid dehydrogenase type 1 (HSD3B1), and human chorionic gonadotropin
      (HCG) was detected by western blot analysis. Furthermore, the proliferation,
      invasion/migration, and apoptosis of cells were analyzed by the cell counting kit
      8 assay, transwell assay, and flow cytometry, respectively. The results showed
      that overexpression of miR-320a decreased the optical density (OD) values and the
      proliferation rate of HTR.8/SVneo cells and HUVECs, while inhibiting the
      expression of VEGF, Ang-1, HSD3B1, and HCG in these cells. Furthermore, miR-320a
      reduced the ability of cell invasion and migration, while increasing the rate of
      cell apoptosis. After cotransfecting the cells with miR-320a and ERRgamma small
      (or short) interfering RNA (siRNA), the decreased ERRgamma expression led to
      inhibited proliferation, migration, and invasion, but increased apoptosis of
      HTR.8/SVneo cells and HUVECs. Our results further revealed that miR-320a induced
      the apoptosis of trophoblasts and endothelial cells while inhibiting their
      proliferation, migration, and invasion by decreasing the expression of ERRgamma
      and by indirectly suppressing the expression of VEGF, Ang-1, HSD3B1, and HCG.

PMID- 30216442
TI  - LncRNA DGCR5 represses the development of hepatocellular carcinoma by targeting
      the miR-346/KLF14 axis.
AB  - Long non-coding RNAs (lncRNAs) are a class of regulatory noncoding RNAs. Emerging
      evidence highlights the critical roles of lncRNAs in the progression of
      hepatocellular carcinoma (HCC). Although many lncRNAs have been identified in the
      development of HCC, the association between DiGeorge syndrome critical region
      gene 5 (DGCR5) and HCC remains unclear. In the current study, we focused on the
      biological role of DGCR5 in HCC. We observed that DGCR5 was decreased in HCC
      cells, including SMCC7721, Hep3B, HepG2, MHCC-97L, MHCC-97H, and SNU449
      hepatocellular carcinoma cells, compared with the normal human liver cell line
      THLE-3 normal human liver cells. In addition, DGCR5 overexpression could repress
      HCC cell growth, migration, and invasion considerably. Increasing studies have
      indicated the interactions between lncRNAs and microRNAs. MicroRNAs are
      endogenous small noncoding RNAs and they can play important roles in
      tumorigenesis. MicroRNA 346 (miR-346) has been demonstrated in various human
      cancer types, including HCC. MiR-346 was found to be increased in HCC cells and
      DGCR5 can act as a sponge of miR-346 to modulate the progression of HCC. The
      binding correlation between DGCR5 and miR-346 was validated in our research.
      Subsequently, Kruppel-like factor 14 (KLF14) was predicted as a downstream target
      of miR-346 and miR-346 can induce the development of HCC by inhibiting KLF14.
      Finally, we proved that DGCR5 can rescue the inhibited levels of KLF14 repressed
      by miR-346 mimics in MHCC-97H and Hep3B cells. Taken together, it was indicated
      in our study that DGCR5 can restrain the progression of HCC through sponging miR
      346 and modulating KLF14 in vitro.

PMID- 30216441
TI  - Screening the full leucocyte receptor complex genomic region revealed
      associations with pemphigus that might be explained by gene regulation.
AB  - Pemphigus foliaceus (PF) is a blistering autoimmune skin disease rare in most of
      the world but endemic in certain regions of Brazil. PF is characterized by the
      detachment of epidermal cells and the presence of autoantibodies against
      desmoglein 1. In previous studies, we have shown that genetic polymorphisms and
      variable expression levels of certain leucocyte receptor complex (LRC) genes were
      associated with PF. However, the role of the LRC on PF susceptibility remained to
      be investigated. Here, we analysed 527 tag single nucleotide polymorphisms (SNPs)
      distributed within the 1.5 Mb LRC. After quality control, a total of 176 SNPs
      were analysed in 229 patients with PF and 194 controls. Three SNPs were
      associated with differential susceptibility to PF. The intergenic variant
      rs465169 [odds ratio (OR) = 1.50; P = 0.004] is located in a region that might
      regulate several immune-related genes, including VSTM1, LILRB1/2, LAIR1/2,
      LILRA3/4 and LENG8. The rs35336528 (OR = 3.44; P = 0.009) and rs1865097 (OR =
      0.57; P = 0.005) SNPs in LENG8 and FCAR genes, respectively, were also associated
      with PF. Moreover, we found four haplotypes with SNPs within the KIR3DL2/3, LAIR2
      and LILRB1 genes associated with PF (P < 0.05), which corroborate previously
      reported associations. Thus, our results confirm the importance of the LRC for
      differential susceptibility to PF and reveal new markers that might influence
      expression levels of several LRC genes, as well as candidates for further
      functional studies.

PMID- 30216443
TI  - In Vitro Digestion of Lipids in Real Foods: Influence of Lipid Organization
      Within the Food Matrix and Interactions with Nonlipid Components.
AB  - : In vitro digestion research has scarcely addressed the assessment of the
      complexity of digestion in real food. The aim of the present study was to
      evaluate the influence of intestinal conditions, nonlipid components, and lipid
      organization within the food matrix on lipolysis extent. A selection of 52 foods
      was studied under different simulated intestinal conditions, including those
      related to patients with cystic fibrosis (pH6, bile salts 1 mM due to decreased
      pancreatic and biliary secretions) and to healthy subjects (pH7, bile salts 10
      mM). Linear mixed regression models were applied to explain associations of food
      properties with lipolysis. Normal intestinal conditions allowed for optimal
      lipolysis in most of the foods in contrast to the altered intestinal scenario (30
      compared with 1 food reaching > 90% lipolysis). Lipid-protein and lipid-starch
      interactions were evidenced to significantly affect lipolysis (P < 0.001) in all
      the digestion conditions, decreasing in those foods with low fat and high protein
      or high starch content. In addition, under decreased intestinal pH and bile
      concentration, lipolysis was lower in foods with complex solid structures and
      continuous lipid phase than in the oil-in-water continuous aqueous phase (global
      P < 0.01). However, in the normal conditions lipid organization within the food
      matrix did not show a significant effect on lipolysis (global P = 0.08). In
      conclusion, food properties play a crucial role in lipolysis, which should be
      considered when establishing dietary recommendations. PRACTICAL APPLICATION: Food
      composition, lipid organization within the food matrix, and gastrointestinal
      conditions are key factors affecting lipolysis. Knowledge on that can be used to
      modulate lipolysis performance after food ingestion. Different applications are
      foreseen, as food design and nutritional recommendations for the general
      populations and specific target groups. The most immediate application is related
      to the scope of the research project that frames this work (www.mycyfapp.eu).
      These results have contributed to the development of a mobile app for cystic
      fibrosis patients, which includes an algorithm for enzyme dose prediction based
      on food properties. The app is currently being tested in a clinical trial
      setting.

PMID- 30216444
TI  - Long-Term Outcome of Patients With Intractable Chronic Cluster Headache Treated
      With Injection of Onabotulinum Toxin A Toward the Sphenopalatine Ganglion - An
      Observational Study.
AB  - OBJECTIVES: To investigate long-term outcomes in per-protocol chronic cluster
      headache patients (n = 7), 18 and 24 months after participation in "Pilot study
      of sphenopalatine injection of onabotulinumtoxinA for the treatment of
      intractable chronic cluster headache." METHODS: Data were collected prospectively
      through headache diaries, HIT-6, and open questionnaire forms at 18 and 24 months
      after the first treatment. Patients had access to repeated injections when
      needed. RESULTS: An overall significant reduction in cluster headache attack
      frequency per month (57.3 +/- 35.6 at baseline vs 12.4 +/- 15.2 at month 18 and
      24.6 +/- 19.2 at month 24) was found. In addition, there was a reduction in
      attacks with severe and unbearably intensity (50.0 +/- 38.3 at baseline vs 10.1
      +/- 14.7 at month 18 and 16.6 +/- 13.7 at month 24) and an increase in attack
      free days (4.2 +/- 5.9 at baseline vs 19.1 +/- 9.4 at month 18 and 12.9 +/- 8.8
      at month 24). CONCLUSIONS: Our findings suggest sustained headache relief after
      repeated onabotulinumtoxinA injections toward the sphenopalatine ganglion in
      intractable chronic cluster headache. A placebo-controlled trial with long-term
      follow-up is warranted.

PMID- 30216445
TI  - Daily Posttraumatic Stress Disorder Symptom Accommodation and Relationship
      Functioning in Military Couples.
AB  - Romantic partners' accommodation of trauma survivors' posttraumatic stress
      disorder (PTSD) symptoms (e.g., taking on tasks, survivors avoid participating in
      social withdrawal) is associated with lower relationship satisfaction for both
      partners and survivors. Little is known about associations of partner
      accommodation with other aspects of relationship functioning, like intimacy.
      Sixty-four male military veterans with at least subclinical PTSD and their
      partners participated in a 2-week daily diary study. Veterans completed nightly
      measures of PTSD symptoms, while female partners completed nightly measures of
      accommodating behaviors performed that day. Both partners reported feelings of
      intimacy each night. Multilevel models revealed that accommodation was
      significantly, negatively associated with feelings of intimacy, with stronger
      effects for partners (t = -8.70) than for veterans (t = -5.40), and stronger
      effects when veterans had lower (t = -7.43) rather than higher (t = -5.20) levels
      of daily PTSD symptoms. Therapists should consider accommodating behaviors as a
      potential impediment to relationship intimacy, particularly when veterans have
      less severe symptoms of PTSD. Accommodating behaviors are an ideal treatment
      target in behavioral couple therapies.

PMID- 30216446
TI  - Effects of drought and fire on resprouting capacity of 52 temperate Australian
      perennial native grasses.
AB  - It remains uncertain how perennial grasses with different photosynthetic pathways
      respond to fire, and how this response varies with stress at the time of burning.
      Resprouting after fire was examined in relation to experimentally manipulated pre
      fire watering frequencies. We asked the following questions: are there response
      differences to fire between C3 and C4 grasses? And, how does post-fire
      resprouting vary with pre-fire drought stress? Fifty-two perennial Australian
      grasses (37 genera, 13 tribes) were studied. Three watering frequencies were
      applied to simulate increasing drought. Pre-fire tiller number, tiller density,
      specific leaf area and leaf dry matter content were measured as explanatory
      variables to assess response. Most species (90%) and individuals (79%) resprouted
      following experimental burning. C4 grasses had higher probabilities of surviving
      fire relative to C3 grasses. Responses were not related to phylogeny or tribe.
      High leaf dry matter content reduced the probability of dying, but also reduced
      the re-emergence of tillers. Post-fire tiller number increased with increasing
      drought, regardless of photosynthetic type, suggesting that drought plays a role
      in the ability of grasses to recover after fire. This has implications for
      understanding the persistence of species in landscapes where fire management is
      practiced.

PMID- 30216447
TI  - Redox proteomics and amyloid beta-peptide: insights into Alzheimer disease.
AB  - Alzheimer disease (AD) is a progressive neurodegenerative disorder associated
      with aging and characterized pathologically by the presence of senile plaques,
      neurofibrillary tangles, and neurite and synapse loss. Amyloid beta-peptide (1
      42) [Abeta(1-42)], a major component of senile plaques, is neurotoxic and induces
      oxidative stress in vitro and in vivo. Redox proteomics has been used to identify
      proteins oxidatively modified by Abeta(1-42) in vitro and in vivo. In this
      review, we discuss these proteins in the context of those identified to be
      oxidatively modified in animal models of AD, and human studies including familial
      AD, pre-clinical AD (PCAD), mild cognitive impairment (MCI), early AD, late AD,
      Down syndrome (DS), and DS with AD (DS/AD). These redox proteomics studies
      indicate that Abeta(1-42)-mediated oxidative stress occurs early in AD
      pathogenesis and results in altered antioxidant and cellular detoxification
      defenses, decreased energy yielding metabolism and mitochondrial dysfunction,
      excitotoxicity, loss of synaptic plasticity and cell structure,
      neuroinflammation, impaired protein folding and degradation, and altered signal
      transduction. Improved access to biomarker imaging and the identification of
      lifestyle interventions or treatments to reduce Abeta production could be
      beneficial in preventing or delaying the progression of AD. This article is part
      of the Proteomics special issue.

PMID- 30216448
TI  - Lactobacillus reuteri F-9-35 Prevents DSS-Induced Colitis by Inhibiting
      Proinflammatory Gene Expression and Restoring the Gut Microbiota in Mice.
AB  - : Probiotics are considered to be a potential treatment for ulcerative colitis
      (UC). The aim of this study was to compare the preventive effect of a space
      flight-induced mutant L. reuteri F-9-35 and its wild type on UC in vivo. Female
      mice were randomly assigned to five groups: one normal and four colitic. Mice
      from colitis groups were daily gavaged with 0.2 mL 12% (w/v) skim milk containing
      the mutant or wild type (1 * 1011 CFU/mL), skim milk alone or distilled water for
      the whole experiment period, starting 7 days before colitis induction. UC was
      induced by administrating mice with 3.5% (w/v) dextran sulfate sodium (DSS) in
      drinking water for 7 days, after which DSS was removed and maintained for 3 days
      as a recovery phase. The results showed that the mice fed with L. reuteri F-9-35
      had less inflammatory phenotype according to macroscopic and histological
      analysis, reduced myeloperoxidase activity, and lower expression of
      proinflammatory genes (Tumor necrosis factor-alpha, cyclooxygenase-2 and
      interleukin-6) in colonic tissue compared with control. Furthermore, L. reuteri F
      9-35 protected the mice from gut microbiota dysbiosis from DDS induced colitis.
      Neither wild type nor the milk alone had such beneficial effects. From above we
      conclude that L. reuteri F-9-35 has great potential in the prevention of UC as a
      dietary supplement. PRACTICAL APPLICATION: Ulcerative colitis (UC) is the most
      common inflammatory bowel diseases and there is still a lack of safe and
      effective treatments. Consumption of L. reuteri F-9-35 may effective in
      preventing human UC.

PMID- 30216449
TI  - Antimicrobial effects of mesenchymal stem cells primed by modified LPS on
      bacterial clearance in sepsis.
AB  - BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs)-based regenerative
      therapy is now considered as an alternative approach to revive infectious
      diseases, including sepsis. Nevertheless, the efficiency of MSC application is
      limited by the poor survival rate of engrafted MSCs. Hence, preconditioning was
      established as a strategy to increase the cells' efficiency. METHODS: MSCs were
      preconditioned with 1 MUg/ml of three different lipopolysaccharides (LPSs) of
      Pseudomonas (Pse-LPS), Acinetobacter (Ac-LPS), and Acinetobacter inactivated
      lipid A by PagL (Ac-LPS-PagL). Then, preconditioned MSCs were exposed to
      oxidative stress and serum deprivation followed by evaluation of the
      antibacterial activity, survival, and apoptosis of MSCs. Then, the murine sepsis
      model treated with 100 MUl phosphate-buffered saline (control group, sepsis
      group), 100 MUl of 1 * 10 6 wild MSCs (MSC group), and three remained groups
      received 100 MUl of 1 * 10 6 LPS-preconditioned MSCs (Pse-LPS-MSCs group: LPS
      purified from Pseudomonas, or Ac-LPS-MSCs group: LPS purified from Acinetobacter,
      and Ac-PagL-LPS-MSCs group: detoxified LPS Pagl). RESULTS: After 4 days, LPS
      preconditioned MSC transplantation modulated the immune response and reduced
      inflammation in septic mice. Apoptosis of Pse-LPS/Ac-LPS-preconditioned-MSCs was
      obviously reduced in vitro, and the survival rate of engrafted mice was evidently
      elevated in Pse-LPS-MSCs and Ac-LPS-MSCs groups compared with other three groups.
      CONCLUSION: LPS preconditioning provides an innovative strategy for evolving
      functional and biological properties of MSCs and ameliorates the survival rate of
      the mouse model of sepsis after MSC transplantation, protects cells from
      apoptosis and organ damages, and evaluates therapeutic properties, including
      immunemodulatory.

PMID- 30216450
TI  - Surgical trauma-induced CCL18 promotes recruitment of regulatory T cells and
      colon cancer progression.
AB  - BACKGROUND: Surgical stress has been suggested to facilitate colon cancer growth
      and metastasis. However, the precise mechanisms by which surgical trauma promotes
      colon cancer progression remain poorly understood. METHODS: To unravel the
      mechanisms underlying surgery-induced colon cancer progression, a syngenic
      transplantation tumor model was established with CT26 cells, and the effect of
      laparotomy on tumor progression was investigated. Especially, the expression of
      several chemokines was assessed, and their roles in recruiting CD4+ CD25+
      regulatory T cells (Tregs) after surgery were analyzed. RESULTS: Tregs population
      was significantly increased in the tumor tissue and peripheral blood of tumor
      bearing mice after laparotomy. C-C motif chemokine ligand 18 (CCL18) expression
      was significantly upregulated after laparotomy in tumor tissue and the peritoneal
      cavity of tumor-bearing mice, and it was positively correlated with the
      recruitment of Tregs. Functionally, CCL18 knockdown significantly reduces tumor
      growth and angiogenesis compared with control. Through analysis of Tregs, we
      found an upregulated proportion of Tregs in tumor tissue, peritoneal cavity, and
      peripheral blood after laparotomy, but this enhancement was blocked after CCL18
      knockdown. In patients with colon cancer, a higher Tregs proportion is positively
      correlated to more advanced clinical TNM stages and shorter survival.
      Furthermore, a positive correlation was found between the serum CCL18 level and
      the Treg proportion in clinical samples. CONCLUSION: Surgical trauma contributes
      to colon cancer progression by increasing CCL18 expression and hence promotes
      Treg recruitment, which leads to an immunosuppressive environment.

PMID- 30216451
TI  - Functions of stone cells and oleoresin terpenes in the conifer defense syndrome.
AB  - Conifers depend on complex defense systems against herbivores. Stone cells (SC)
      and oleoresin are physical and chemical defenses of Sitka spruce that have been
      separately studied in previous work. Weevil oviposit at the tip of the previous
      year's apical shoot (PYAS). We investigated interactions between weevil larvae
      and trees in controlled oviposition experiments with resistant (R) and
      susceptible (S) Sitka spruce. R trees have an abundance of SC in the PYAS cortex.
      SC are mostly absent in S trees. R trees and S trees also differ in the
      composition of oleoresin terpenes. Transcriptomes of R and S trees revealed
      differences in long-term weevil-induced responses. Performance of larvae was
      significantly reduced on R trees compared with S trees under experimental
      conditions that mimicked natural oviposition behavior at apical shoot tips and
      may be attributed to the effects of SC. In oviposition experiments designed for
      larvae to feed below the area of highest SC abundance, larvae showed an unusual
      feeding behavior and oleoresin appeared to function as the major defense. The
      results support a role for both SC and oleoresin terpenes and possible synergies
      between these traits in the defense syndrome of weevil-resistant Sitka spruce.

PMID- 30216452
TI  - Downregulation of mitochondrial alternative oxidase affects chloroplast function,
      redox status and stress response in a marine diatom.
AB  - Diatom dominance in contemporary aquatic environments indicates that they have
      developed unique and effective mechanisms to cope with the rapid and considerable
      fluctuations that characterize these environments. In view of their evolutionary
      history from a secondary endosymbiosis, inter-organellar regulation of
      biochemical activities may be of particular relevance. Diatom mitochondrial
      alternative oxidase (AOX) is believed to play a significant role in supplying
      chloroplasts with ATP produced in the mitochondria. Using the model diatom
      Phaeodactylum tricornutum we generated AOX knockdown lines, and followed
      sensitivity to stressors, photosynthesis and transcriptome and metabolome
      profiles of wild-type and knockdown lines. We show here that expression of the
      AOX gene is upregulated by various stresses including H2 O2 , heat, high light
      illumination, and iron or nitrogen limitation. AOX knockdown results in
      hypersensitivity to stress. Knockdown lines also show significantly reduced
      photosynthetic rates and their chloroplasts are more oxidized. Comparisons of
      transcriptome and metabolome profiles suggest a strong impact of AOX activity on
      gene expression, which is carried through to the level of the metabolome. Our
      data provide evidence for the involvement of mitochondrial AOX in processes
      central to the cell biology of diatoms, revealing that cross-talk between
      mitochondria and chloroplasts is crucial for maintaining sensitivity to changing
      environments.

PMID- 30216453
TI  - Competition for epidermal space in the evolution of leaves with high
      physiological rates.
AB  - Leaves with high photosynthetic capacity require high transpiration capacity.
      Consequently, hydraulic conductance, stomatal conductance, and assimilation
      capacities should be positively correlated. These traits make independent demands
      on anatomical space, particularly due to the propensity for veins to have bundle
      sheath extensions that exclude stomata from the local epidermis. We measured
      density and area occupation of bundle sheath extensions, density and size of
      stomata and subsidiary cells, and venation density for a sample of extant
      angiosperms and fossil and living nonangiosperm tracheophytes. For most
      nonangiosperms, even modest increases in vein density and stomatal conductance
      would require substantial reconfigurations of anatomy. One characteristic of the
      angiosperm syndrome (e.g. small cell sizes, etc.) is hierarchical vein networks
      that allow expression of bundle sheath extensions in some, but not all veins,
      contrasting with all-or-nothing alternatives available with the single-order vein
      networks in most nonangiosperms. Bundle sheath modulation is associated with
      higher vein densities in three independent groups with hierarchical venation:
      angiosperms, Gnetum (gymnosperm) and Dipteris (fern). Anatomical and
      developmental constraints likely contribute to the stability in leaf
      characteristics - and ecophysiology - seen through time in different lineages and
      contribute to the uniqueness of angiosperms in achieving the highest vein
      densities, stomatal densities, and physiological rates.

PMID- 30216454
TI  - D. Walter Cohen, DDS: A visionary and gifted leader.

PMID- 30216456
TI  - Spontaneous epimutations in plants.
AB  - Contents Summary I. Introduction II. What is the rate and molecular spectrum of
      spontaneous epimutations? III. Do spontaneous epimutations have phenotypic
      consequences? IV. Conclusion and discussion Acknowledgements References SUMMARY:
      Heritable gains or losses of cytosine methylation can arise stochastically in
      plant genomes independently of DNA sequence changes. These so-called 'spontaneous
      epimutations' appear to be a byproduct of imperfect DNA methylation maintenance
      and epigenome reinforcement events that occur in specialized cell types. There is
      continued interest in the plant epigenetics community in trying to understand the
      broader implications of these stochastic events, as some have been shown to
      induce heritable gene expression changes, shape patterns of methylation diversity
      within and among plant populations, and appear to be responsive to multi
      generational environmental stressors. In this paper we synthesized our current
      knowledge of the molecular basis and functional consequences of spontaneous
      epimutations in plants, discuss technical and conceptual challenges, and
      highlight emerging research directions.

PMID- 30216458
TI  - Transcriptomic and proteomic approaches to explore the differences in monoterpene
      and benzenoid biosynthesis between scented and unscented genotypes of
      wintersweet.
AB  - Wintersweet (Chimonanthus praecox L.) is an important ornamental plant in China
      with a pleasant floral scent. To explore the potential mechanisms underlying
      differences in the fragrances among genotypes of this plant, we analyzed floral
      volatile organic compounds (VOCs) from two different genotypes: SW001, which has
      little to no fragrance, and the scented genotype H29. The major VOCs in H29 were
      linalool, trans-beta-ocimene, benzyl acetate, methyl salicylate, benzyl alcohol
      (BAlc) and methyl benzoate. The most important aroma-active compound in H29,
      linalool, was emitted at a low concentration in SW001, which had markedly higher
      levels of trans-beta-ocimene than H29. Next, to investigate scent biosynthesis,
      we analyzed the transcriptome and proteome of fully open flowers of the two
      genotypes. A total of 14 443 differentially expressed unigenes and 196
      differentially expressed proteins were identified. Further analyses indicated
      that 56 differentially expressed genes involved in the terpenoid and benzenoid
      biosynthesis pathways might play critical roles in regulating floral fragrance
      difference. Disequilibrium expression of four terpene synthase genes resulted in
      diverse emission of linalool and trans-beta-ocimene in both genotypes. In
      addition, the expressions of two CpMYC2 transcription factors were both
      upregulated in H29, implying that they may regulate linalool production. Notably,
      16 of 20 genes in the benzenoid biosynthesis pathway were downregulated,
      corresponding to the relatively low level of benzenoid production in SW001. The
      lack of benzyl acetate might indicate that SW001 may lack substrate BAlc or
      functional acetyl-CoA:benzylalcohol acetyltransferase.

PMID- 30216455
TI  - Fluorescent-guided surgery for sentinel lymph node detection in gastric cancer
      and carcinoembryonic antigen targeted fluorescent-guided surgery in colorectal
      and pancreatic cancer.
AB  - Sentinel lymph node procedures for gastric cancer resections using indocyanine
      green (ICG) linked to Nanocoll outperformed normal ICG but did not provide
      information on possible lymph node metastasis. Carcinoembryonic antigen targeted
      fluorescent imaging using SGM-101 was successful in both pancreatic and
      colorectal cancer. A large phase III multicentre trial will soon be initiated in
      colorectal cancer patients.

PMID- 30216457
TI  - Periodontitis causes abnormalities in the liver of rats.
AB  - BACKGROUND: Periodontitis not only causes injury to the periodontium, but also
      damages other tissues such as: articulate, renal, cardiac, and hepatic. The
      objective of this study was to investigate periodontitis induced alterations in
      liver function and structure using an experimental model. METHODS: Twenty female
      rats (Rattus norvegicus) were allocated into two groups: control and
      periodontitis. Gingival bleeding index and oxidative stress parameters and
      specific circulating biomarkers were measured. Immunohistochemistry was carried
      out using alkaline phosphatase (AlkP) staining of the liver. Hepatic tissues,
      cytokines, and lipid contents were measured. Histopathologic evaluation of the
      liver was carried out using light and electron microscopy. RESULTS: Liver
      histopathologic and immunohistochemistry assessment showed increase in steatosis
      score, and presence of binucleate hepatocytes and positive cells for AlkP in
      periodontitis versus control group. Ultrastructural evaluation showed significant
      increase in size and number of lipid droplets (LD), distance between the cisterns
      of rough endoplasmic reticulum (RER), mitochondria size, foamy cytoplasm, and
      glycogen accumulation in the liver of the periodontitis group compared with the
      control group. In addition, plasma levels of AlkP, high-density lipoprotein
      (HDL), triglycerides, and total cholesterol were also changed. CONCLUSION:
      Experimental periodontitis caused immunohistochemistry, histopathologic,
      ultrastructural, oxidative, and biochemical changes in the liver of rats.

PMID- 30216459
TI  - Why Name Generators with a Fixed Number of Alters may be a Pragmatic Option for
      Personal Network Analysis.
AB  - Social network analysis has grown exponentially in recent years, giving rise to
      methodological innovations in different scientific disciplines. In psychology,
      social network analysis has been incorporated into studies of individual
      personality differences and has generated novel areas, such as network
      psychometrics and network interventions. In community psychology, a recent review
      examined the use of network analysis in American Journal of Community Psychology
      publications (Neal & Neal, American Journal of Community Psychology, 2017, 60,
      279). Based on their study, the authors advise researchers to avoid using the
      fixed-choice name generator when possible, as one of the five methodological
      recommendations proposed. In this essay, I explain how the recent increase of
      name generators with a fixed number of alters when studying personal networks is
      originally linked to an interest in describing structural properties. Second, I
      analyze the pragmatic contributions of this method: establishing a limit of
      alters a priori can entail advantages in terms of standardization and
      comparability of personal networks. Finally, to contextualize the methodological
      debate, I argue that personal networks represent the diversity of contexts in
      which the individual participates and are naturally integrated into community
      surveys.

PMID- 30216460
TI  - Toward an Ethical Reflective Practice of a Theory in the Flesh: Embodied
      Subjectivities in a Youth Participatory Action Research Mural Project.
AB  - The focus of this paper is to demonstrate how embodied subjectivities shape
      research experiences. Through an autoethnography of my involvement in a Youth
      Participatory Action Research (YPAR) after-school program with low-income and
      working-class youth of Color from predominantly Latinx communities I examined my
      embodied subjectivities, via an ethical reflective practice, as these surfaced in
      the research context. Autoethnography is presented as a tool to facilitate an
      ethical reflective practice that aligns with heart-centered work. Drawing from an
      epistemology of a theory in the flesh (Anzaldua & Moraga, 1981), embodied
      subjectivities are defined by the lived experiences felt and expressed through
      the body, identities, and positionalities of the researcher. The article
      concludes with implications for the development of community psychology
      competencies that attend to the researcher's embodied subjectivities.

PMID- 30216461
TI  - SND1 expression in breast cancer tumors is associated with poor prognosis.
AB  - Staphylococcal nuclease domain-containing 1 (SND1) expression is crucial for
      breast cancer metastasis; however, the clinical implications of SND1 expression
      in breast cancer remain unclear. This study investigated the relationship of SND1
      protein expression both with metastasis and the prognoses of 144 breast cancer
      patients over a 10-year follow-up. Chi-square tests revealed that the percentages
      of positive SND1 expression in breast cancer tumors were significantly associated
      with larger tumor size (>2 cm, P = 0.043), higher clinical TNM stage (P = 0.003),
      and positive lymph node metastasis (P = 0.001). Breast cancer patients with
      positive SND1 expression had a significantly shorter overall survival and disease
      free survival than those with negative SND1 expression (P < 0.01). Multiple Cox
      regression analysis indicated that SND1 expression is an independent risk factor
      for shorter disease-free survival (hazard ratio = 1.97, P = 0.014). The
      percentages of SND1 expression in metastatic breast cancers were significantly
      higher than that in primary tumors in 30 patients with advanced breast cancer (P
      = 0.016). Therefore, SND1 protein expression is significantly associated with
      breast cancer metastasis and may serve as a biomarker for prognosis of breast
      cancer patients.

PMID- 30216462
TI  - Comparative study of algorithms for synthetic CT generation from MRI:
      Consequences for MRI-guided radiation planning in the pelvic region.
AB  - PURPOSE: Magnetic resonance imaging (MRI)-guided radiation therapy (RT) treatment
      planning is limited by the fact that the electron density distribution required
      for dose calculation is not readily provided by MR imaging. We compare a
      selection of novel synthetic CT generation algorithms recently reported in the
      literature, including segmentation-based, atlas-based and machine learning
      techniques, using the same cohort of patients and quantitative evaluation
      metrics. METHODS: Six MRI-guided synthetic CT generation algorithms were
      evaluated: one segmentation technique into a single tissue class (water-only),
      four atlas-based techniques, namely, median value of atlas images (ALMedian),
      atlas-based local weighted voting (ALWV), bone enhanced atlas-based local
      weighted voting (ALWV-Bone), iterative atlas-based local weighted voting (ALWV
      Iter), and a machine learning technique using deep convolution neural network
      (DCNN). RESULTS: Organ auto-contouring from MR images was evaluated for bladder,
      rectum, bones, and body boundary. Overall, DCNN exhibited higher segmentation
      accuracy resulting in Dice indices (DSC) of 0.93 +/- 0.17, 0.90 +/- 0.04, and
      0.93 +/- 0.02 for bladder, rectum, and bones, respectively. On the other hand,
      ALMedian showed the lowest accuracy with DSC of 0.82 +/- 0.20, 0.81 +/- 0.08, and
      0.88 +/- 0.04, respectively. DCNN reached the best performance in terms of
      accurate derivation of synthetic CT values within each organ, with a mean
      absolute error within the body contour of 32.7 +/- 7.9 HU, followed by the
      advanced atlas-based methods (ALWV: 40.5 +/- 8.2 HU, ALWV-Iter: 42.4 +/- 8.1 HU,
      ALWV-Bone: 44.0 +/- 8.9 HU). ALMedian led to the highest error (52.1 +/- 11.1
      HU). Considering the dosimetric evaluation results, ALWV-Iter, ALWV, DCNN and
      ALWV-Bone led to similar mean dose estimation within each organ at risk and
      target volume with less than 1% dose discrepancy. However, the two-dimensional
      gamma analysis demonstrated higher pass rates for ALWV-Bone, DCNN, ALMedian and
      ALWV-Iter at 1%/1 mm criterion with 94.99 +/- 5.15%, 94.59 +/- 5.65%, 93.68 +/-
      5.53% and 93.10 +/- 5.99% success, respectively, while ALWV and water-only
      resulted in 86.91 +/- 13.50% and 80.77 +/- 12.10%, respectively. CONCLUSIONS:
      Overall, machine learning and advanced atlas-based methods exhibited promising
      performance by achieving reliable organ segmentation and synthetic CT generation.
      DCNN appears to have slightly better performance by achieving accurate automated
      organ segmentation and relatively small dosimetric errors (followed closely by
      advanced atlas-based methods, which in some cases achieved similar performance).
      However, the DCNN approach showed higher vulnerability to anatomical variation,
      where a greater number of outliers was observed with this method. Considering the
      dosimetric results obtained from the evaluated methods, the challenge of electron
      density estimation from MR images can be resolved with a clinically tolerable
      error.

PMID- 30216464
TI  - Busy Streets Theory: The Effects of Community-engaged Greening on Violence.
AB  - Lack of maintenance on vacant neighborhood lots is associated with higher levels
      of depression, anxiety, and stress for nearby residents. Overgrown grasses and
      dense brush provide hiding spots for criminals and space to conduct illicit
      activities. This study builds upon previous research by investigating greening
      programs that engage community members to conduct routine maintenance on vacant
      lots within their neighborhoods. The Clean & Green program is a community-based
      solution that facilitates resident-driven routine maintenance of vacant lots in a
      midsized, Midwestern city. We use mixed effects regression to compare assault and
      violent crime counts on streets where vacant lot(s) are maintained by community
      members (N = 216) versus streets where vacant lots were left alone (N = 446) over
      a 5-year timeframe (2009-2013). Street segments with vacant lots maintained
      through the Clean & Green program had nearly 40% fewer assaults and violent
      crimes than street segments with vacant, abandoned lots, which held across 4
      years with a large sample and efforts to test counterfactual explanations.
      Community-engaged greening programs may not only provide a solution to vacant lot
      maintenance, but also work as a crime prevention or reduction strategy. Engaging
      the community to maintain vacant lots in their neighborhood reduces costs and may
      increase the sustainability of the program.

PMID- 30216463
TI  - Carotid Artery Calcification on Orthopantomograms (CACO Study) - is it indicative
      of carotid stenosis?
AB  - : It is unclear whether incidental carotid artery calcification (CAC) on
      radiographs has a defined relationship to clinically significant carotid artery
      stenosis, and therefore risk of stroke. The primary objective of this study was
      to ascertain the relationship between dental radiograph detected carotid
      calcification and carotid artery stenoses >=50% on carotid duplex ultrasound. We
      carried out an observational study of patients undergoing routine dental
      orthopantomogram (OPG) examinations. Consecutive patients with CAC on OPG were
      prospectively matched to those without CAC based on age and gender. Ultrasound of
      the carotid arteries was performed to determine the presence of stenosis (>=50%)
      in either vessel. Of 5780 consecutive OPG examinations with suitable images for
      analysis, CAC was detected in 10.8%. A total of 233 patients underwent carotid
      ultrasound (130 with and 103 without CAC on OPG). The prevalence of a clinically
      significant (>=50%) carotid stenosis on ultrasound was 15.4% (20/130) in those
      with CAC and 5.8% (6/103) for those without CAC on OPG. Incidental CAC detected
      on routine OPG requires both radiological reporting and clinical follow-up since
      1 in 7 patients will have a clinically significant carotid artery stenosis as
      compared with 1 in 20 patients who do not have CAC. TRIAL REGISTRATION:
      Australian and New Zealand Clinical Trials Registry website (U1111-1148-1066).
      http://www.ANZCTR.org.au/ACTRN12613001038785.aspx.

PMID- 30216466
TI  - Independent and combined abiotic stresses affect the physiology and expression
      patterns of DREB genes differently in stress-susceptible and resistant genotypes
      of banana.
AB  - In tropics, combined stresses of drought and heat often reduce crop productivity
      in plants like Musa acuminata L. We compared responses of two contrasting banana
      genotypes, namely the drought-sensitive Grand Nain (GN; AAA genome) and drought
      tolerant Hill banana (HB; AAB genome) to individual drought, heat and their
      combination under controlled and field conditions. Drought and combined drought
      and heat treatments caused greater reduction in leaf relative water content and
      greater increase in ion leakage and H2 O2 content in GN plants, especially in
      early stages, while the responses were more pronounced in HB at later stages. A
      combination of drought and heat increased the severity of responses. Real-time
      expression patterns of the A-1 and A-2 group DEHYDRATION-RESPONSIVE ELEMENT
      BINDING (DREB) genes revealed greater changes in expression in leaves of HB
      plants for both the individual stresses under controlled conditions compared to
      GN plants. A combination of heat and drought, however, activated most DREB genes
      in GN but surprisingly suppressed their expression in HB in controlled and field
      conditions. Its response seems correlated to a better stomatal control over
      transpiration in HB and a DREB-independent pathway for the more severe combined
      stresses unlike in GN. Most of the DREB genes had abscisic acid (ABA)-responsive
      elements in their promoters and were also activated by ABA suggesting at least
      partial dependence on ABA. This study provides valuable information on
      physiological and molecular responses of the two genotypes to individual and
      combined drought and heat stresses.

PMID- 30216465
TI  - Use of a laser-guided collimation system to perform direct kilovoltage x-ray
      spectra measurements on a linear accelerator onboard imager.
AB  - PURPOSE: The increased use of image-guided radiation therapy (IGRT) has led to
      increased use of kV on board imaging (OBI) devices. At present, directly measured
      OBI beam quality data have only been reported in terms of half-value layers
      (HVL). However, the HVL metric alone does not give the full OBI energy spectra as
      needed for accurate beam modeling. Although direct kV spectrometer devices exist
      they typically suffer from detector pile-up when used with OBI sources. We
      therefore present, for the first time, a novel laser-guided collimation system
      that allows direct measurement of the full energy spectrum for clinical OBI
      systems. METHODS: Several clinically relevant spectra (80, 100, and 125 kVp),
      with and without the half bow-tie filter, were measured using a thermoelectric
      cooled cadmium telluride (CdTe) detector paired with a multichannel analyzer. To
      prevent detector saturation, the photon flux at the detector was reduced by use
      of an in-house designed laser-guided collimation system. After applying energy
      bin corrections, direct spectroscopic measurements were compared to Monte Carlo
      (MC) simulated spectra in order to verify accuracy of collected data. Both
      percent depth dose (PDD) curves and digitally reconstructed radiographs (DRR)
      were compared using the measured vs MC spectra. RESULTS: Measured and MC spectra
      agree with RMSD between 1.96% and 3.29%. PDD curves generated from the measured
      and MC spectra were found to match except for in the small buildup region, with
      an overall match for the six beams ranging between 0.3% and 2.7% RMSD. DRRs
      matched well with a maximum difference in contrast of 1.1% and RMSD of 0.46%
      contrast for various materials in DRRs. CONCLUSIONS: The use of a laser-guided
      collimation system provided a method for quickly obtaining highly accurate kV
      spectrum data from OBI sources. For kV dose or DRR calculation, it was found that
      both spectra produced similar results.

PMID- 30216467
TI  - Increased Plasma-Free Hemoglobin Levels Identify Hemolysis in Patients With
      Cardiogenic Shock and a Trans valvular Micro-Axial Flow Pump.
AB  - Hemolysis is a potential limitation of percutaneously delivered left-sided
      mechanical circulatory support pumps, including trans valvular micro-axial flow
      pumps (TVP). Hemolytic biomarkers among durable left ventricular assist devices
      include lactate dehydrogenase (LDH) >2.5 times the upper limit of normal (ULN)
      and plasma-free hemoglobin (pf-Hb) >20 mg/dL. We examined the predictive value of
      these markers among patients with cardiogenic shock (CS) receiving a TVP. We
      retrospectively studied records of 116 consecutive patients receiving an Impella
      TVP at our institution between 2012 and 2017 for CS. Twenty-three met
      inclusion/exclusion criteria, and had sufficient pf-Hb data for analysis. Area
      under receiver-operator characteristic (ROC) curve for diagnosing hemolysis were
      calculated. Mean age was 62 +/- 14 years and ejection fraction was 15 +/- 5%.
      Mean duration of support was 5.4 +/- 3.5 days. Pre-device LDH levels were >2.5x
      ULN in 71% (n = 5/7) of 5.0 and 29% of CP patients, while pre-device pf-Hb levels
      were >20 mg/dL in 14% (n = 1/7) of 5.0 and 25% (n = 4/16) of CP patients. Given
      elevated baseline LDH and pf-Hb levels, we defined hemolysis as a pf-Hb level >40
      mg/dL within 72 h post-implant plus clinical evidence of device-related
      hemolysis. We identified that 30% (n = 7/23) had device-related hemolysis. Using
      ROC curve-derived cut-points, an increase in delta pf-Hb by >27mg/dL, not delta
      LDH, within 24 h after TVP implant (delta pf-Hb: C-statistic = 0.79, sensitivity:
      57%, specificity: 93%, p <0.05) was highly predictive of hemolysis. In
      conclusion, we identified a change in pf-Hb, not LDH, levels is highly sensitive
      and specific for hemolysis in patients treated with a TVP for CS.

PMID- 30216468
TI  - Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI
      position paper.
AB  - NSAID-exacerbated respiratory disease (N-ERD) is a chronic eosinophilic,
      inflammatory disorder of the respiratory tract occurring in patients with asthma
      and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are
      exacerbated by NSAIDs, including aspirin. Despite some progress in understanding
      of the pathophysiology of the syndrome, which affects 1/10 of patients with
      asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In
      order to provide evidence-based recommendations for the diagnosis and management
      of N-ERD, a panel of international experts was called by the EAACI Asthma
      Section. The document summarizes current knowledge on the pathophysiology and
      clinical presentation of N-ERD pointing at significant heterogeneity of this
      syndrome. Critically evaluating the usefulness of diagnostic tools available, the
      paper offers practical algorithm for the diagnosis of N-ERD. Recommendations for
      the most effective management of a patient with N-ERD stressing the potential
      high morbidity and severity of the underlying asthma and rhinosinusitis are
      discussed and proposed. Newly described sub-phenotypes and emerging sub-endotypes
      of N-ERD are potentially relevant for new and more specific (eg, biological)
      treatment modalities. Finally, the document defines major gaps in our knowledge
      on N-ERD and unmet needs, which should be addressed in the future.

PMID- 30216469
TI  - Transurethral ultrasound therapy of the prostate in the presence of
      calcifications: A simulation study.
AB  - PURPOSE: Transurethral ultrasound therapy is an investigational treatment
      modality which could potentially be used for the localized treatment of prostate
      cancer. One of the limiting factors of this therapy is prostatic calcifications.
      These attenuate and reflect ultrasound and thus reduce the efficacy of the
      heating. The aim of this study is to investigate how prostatic calcifications
      affect therapeutic efficacy, and to identify the best sonication strategy when
      calcifications are present. METHODS: Realistic computational models were used on
      clinical patient data in order to simulate different therapeutic situations with
      naturally occurring calcifications as well as artificial calcifications of
      different sizes (1-10 mm) and distances (5-15 mm). Furthermore, different
      sonication strategies were tested in order to deliver therapy to the untreated
      tissue regions behind the calcifications. RESULTS: The presence of calcifications
      in front of the ultrasound field was found to increase the peak pressure by 100%
      on average while the maximum temperature only rose by 9% during a 20-s
      sonication. Losses in ultrasound energy were due to the relatively large acoustic
      impedance mismatch between the prostate tissue and the calcifications (1.63 vs
      3.20 MRayl) and high attenuation coefficient (0.78 vs 2.64 dB/MHz1.1 /cm), which
      together left untreated tissue regions behind the calcifications. In addition,
      elevated temperatures were seen in the region between the transducer and the
      calcifications. Lower sonication frequencies (1-4 MHz) were not able to penetrate
      through the calcifications effectively, but longer sonication durations (20-60 s)
      with selective transducer elements were effective in treating the tissue regions
      behind the calcifications. CONCLUSIONS: Prostatic calcifications limit the reach
      of therapeutic ultrasound treatment due to reflections and attenuation. The
      tissue regions behind the calcifications can possibly be treated using longer
      sonication durations combined with proper transducer element selection. However,
      caution should be taken with calcifications located close to sensitive organs
      such as the urethra, bladder neck, or rectal wall.

PMID- 30216470
TI  - Measuring Sense of Community Responsibility in Community-Based Prevention
      Coalitions: An Item Response Theory Analysis.
AB  - Research on sense of community (SOC) has traditionally been approached from a
      resource perspective. Recently, however, research on the experience of SOC has
      evolved to include a related but distinct construct of sense of community
      responsibility (SOC-R), or feelings of accountability for the well-being of a
      community. This study applied item response theory to examine the psychometric
      properties of a SOC-R scale used in an evaluation of community-based substance
      abuse prevention coalitions. Data were collected in 2017 from coalition members
      (analytic sample = 309) in the northeastern United States. Findings indicate that
      the scale was reliable, unidimensional, and functioned well, particularly at low
      and moderate levels of the construct. The addition of two items intended to
      capture higher levels of the construct improved the scale's functioning at higher
      levels of SOC-R. The adapted SOC-R scale was also shown to have moderately strong
      relationships with conceptually relevant variables, including SOC, coalition
      participation, number of roles performed in the coalition, and engagement in
      community action activities. These findings provide empirical evidence to support
      the reliability and validity of the SOC-R scale, and have critical implications
      for our conceptualization of the SOC construct, its measurement, and for the
      evaluation of community-based prevention interventions.

PMID- 30216471
TI  - Ultrasound in the management of iatrogenic spinal accessory nerve palsy at the
      posterior cervical triangle area.
AB  - INTRODUCTION: The purpose of this study was to evaluate the application of
      ultrasound in the management of iatrogenic spinal accessory nerve palsy at the
      posterior cervical triangle area. METHODS: In this retrospective study, we
      compared ultrasonographic results with intraoperative findings in patients with
      iatrogenic spinal accessory nerve palsy from 2014 to 2018 in our hospital.
      RESULTS: Eleven patients were included. Ultrasound detected nerve transections in
      9 patients and continuities in 2 patients. The ultrasonographic results were
      consistent with the intraoperative findings. Furthermore, ultrasound was able to
      accurately reveal lesion location in 8 of 9 patients with nerve transections.
      DISCUSSION: Ultrasound provides direct images about nerve lesions contributing to
      the diagnosis of iatrogenic spinal accessory nerve palsy at the posterior
      cervical triangle area and also reveals lesion location, assisting in formulating
      suitable surgical plans preoperatively. We recommend that ultrasound be
      integrated into the preoperative evaluation. This article is protected by
      copyright. All rights reserved.

PMID- 30216472
TI  - Neuromuscular ultrasound as a biomarker in amyotrophic lateral sclerosis.

PMID- 30216473
TI  - Going with the flow: Structural determinants of vascular tissue transport
      efficiency and safety.

PMID- 30216474
TI  - Prognostic role of inflammatory biomarkers in HIV-infected patients with a first
      diagnosis of hepatocellular carcinoma: A single-center study.
AB  - OBJECTIVES: To assess hepatocellular carcinoma (HCC) survival and to investigate
      the prognostic role of immunonutritional biomarkers, as neutrophil to lymphocyte
      ratio (NLR), platelet to lymphocyte ratio (PLR) and prognostic nutritional index
      (PNI), in a cohort of human immunodeficiency virus (HIV)-infected patients.
      METHODS: All HIV-positive patients diagnosed with HCC at our Department from
      January 2000 to December 2013 were included. The outcomes were overall survival
      (OS), recurrence-free survival (RFS), and liver-related death (LRD). To examine
      the role of inflammatory biomarkers on the outcomes, univariate and multivariable
      Cox regression models were used. Receiver operating characteristic (ROC) curves
      were implemented to evaluate the prediction role of NLR, PLR, and PNI. RESULTS: A
      total of 40 patients (90% males) with a mean age of 48.3 years (SD = 5.6) were
      recruited. NLR >= 2.9 was associated with all causes mortality, as well as, PLR
      >= 126. NLR and PLR were predictors of OS, RFS, and LRD, while PNI did not emerge
      as a prognostic marker. According to the multivariate analysis, no HCC treatment
      was the only risk factor associated with risk of death. The areas under the ROC
      curves were 68.3 (95% confidence interval [CI], 54.5-82.1) for PLR and 66.3 (95%
      CI, 54.3-78.2) for NLR at 3 years; similar results were found at 5 years of
      follow-up. CONCLUSIONS: Although, if examined singularly, NLR and PLR are
      prognostic factors for HCC recurrence and survival in HIV-infected patients, at
      the multivariate analysis, "no HCC treatment" remains the only independent risk
      factor associated with fatal outcome.

PMID- 30216475
TI  - Phytochrome B dynamics departs from photoequilibrium in the field.
AB  - Vegetation shade is characterized by marked decreases in the red/far-red ratio
      and photosynthetic irradiance. The activity of phytochrome in the field has
      typically been described by its photoequilibrium, defined by the photochemical
      properties of the pigment in combination with the spectral distribution of the
      light. This approach represents an oversimplification because phytochrome B
      (phyB) activity depends not only on its photochemical reactions but also on its
      rates of synthesis, degradation, translocation to the nucleus, and thermal
      reversion. To account for these complex cellular reactions, we used a model to
      simulate phyB activity under a range of field conditions. The model provided
      values of phyB activity that in turn predicted hypocotyl growth in the field with
      reasonable accuracy. On the basis of these observations, we define two scenarios,
      one is under shade, in cloudy weather, at the extremes of the photoperiod or in
      the presence of rapid fluctuations of the light environment caused by wind
      induced movements of the foliage, where phyB activity departs from
      photoequilibrium and becomes affected by irradiance and temperature in addition
      to the spectral distribution. The other scenario is under full sunlight, where
      phyB activity responds mainly to the spectral distribution of the light.

PMID- 30216476
TI  - Conservative versus surgical treatment of 21 sports horses with osseous trauma in
      the proximal phalangeal sagittal groove diagnosed by low-field MRI.
AB  - OBJECTIVE: To compare the outcome following conservative vs surgical management
      of sports horses with a diagnosis of subchondral bone trauma of the proximal
      aspect of the proximal phalanx (PP) by low-field MRI. STUDY DESIGN: Retrospective
      case series. ANIMALS: Twenty-one mature sports horses with evidence of high water
      signal within the proximal sagittal groove of the PP according to low-field MRI
      of the fetlock, with no definitive radiographic evidence of fracture. METHODS:
      Medical records (2010-2017) of horses admitted to 2 referral hospitals were
      reviewed. Historical, clinical, radiographic, and MRI findings and treatment
      choice were recorded. Conservative management consisted of confinement to a stall
      followed by gradual reintroduction to exercise. Surgical management consisted of
      cortical screw fixation across the proximal aspect of the PP. Long-term outcome
      was determined by telephone questionnaire or by clinical records review. Fisher's
      exact test was used to compare outcome between the 2 treatment groups. RESULTS:
      Follow-up was available in 17 of 21 horses in the study, including 8 horses
      treated conservatively and 9 treated surgically. No difference in outcome was
      detected in this study; 4 of 8 horses were sound after conservative management,
      and 5 of 9 horses were sound after surgery (P > .99). CONCLUSION: Approximately
      half of the horses that had a diagnosis of osseous trauma within the proximal
      aspect of PP returned to athletic activity, regardless of conservative or
      surgical management. CLINICAL SIGNIFICANCE: The prognosis for return to athletic
      functions in horses with osseous trauma within the proximal aspect of the PP is
      guarded.

PMID- 30216477
TI  - Outcomes of multidisciplinary treatment planning in US cancer care settings.
AB  - Multidisciplinary treatment planning (MTP) is a process of engaging multiple
      disciplines to develop or refine the disease management plan. It is widely
      implemented in US cancer treatment settings and is considered to have favorable
      effects on both care quality and other outcomes. However, evidence reviews to
      date regarding MTP effectiveness have based their conclusions on studies
      conducted predominantly outside the United States. The authors conducted a
      systematic review of US-based studies to synthesize and critically appraise
      evidence of the effects of MTP on cancer care quality, health services outcomes,
      and survival. Database searches identified studies of MTP outcomes conducted in
      US cancer care settings from 2000 to 2017. Forty-five studies met criteria for
      inclusion. MTP was associated with favorable effects on several indicators of
      cancer care quality, including delivery of guideline-concordant treatment and
      improvements in diagnostic accuracy, staging completeness, surgical technique,
      and timeliness. Effects on survival and clinical trials enrollment were mixed.
      Delivery formats for MTP were generally not well described, and study designs
      were nonrandomized, limiting the ability to identify mediators of intervention
      effects. Continued study is warranted to clarify effective components of MTP
      interventions, and to understand the mechanism(s) through which MTP produces
      favorable effects on outcomes.

PMID- 30216478
TI  - The role of maintenance therapy in patients with diffuse large B cell lymphoma: A
      systematic review and meta-analysis.
AB  - Randomized trials of maintenance therapy (MT) in diffuse large B cell lymphoma
      (DLBCL) are inconclusive regarding its effect on overall survival (OS) and
      disease control. We aimed to examine the efficacy and safety of MT in this meta
      analysis. Systematic review and meta-analysis of randomized controlled trials
      comparing MT with observation or placebo, in patients with DLBCL, who achieved
      complete response (CR) or partial response (PR) after first-line chemotherapy
      with or without rituximab. Primary outcome was OS. Secondary outcomes included
      relapse rate, disease control (defined as progression-free survival, event-free
      survival, or disease-free survival, as reported in the original trials), and
      safety. Our search yielded 14 trials including 5122 patients. Median age of
      patients was 49 to 70 years. Six trials included rituximab as the MT; three
      included Interferon alfa; other trials include thalidomide, lenalidomide,
      cyclophosphamide and prednisone, serine threonine kinase inhibitor enzastaurin,
      and mTOR inhibitor everolimus. MT did not improve OS compared to observation, OR
      0.91, (95% CI 0.78-1.07). Results were the same in a subgroup analysis by the
      type of maintenance (rituximab vs other). MT did decreased relapse rate, RR 0.76
      (95% CI 0.65-0.89) and improved disease control, OR 0.74 (95% CI 0.65-0.84).
      Disease control was significantly improved in the subgroup of studies evaluating
      rituximab as maintenance OR 0.61 (95% CI 0.47-0.79) and in the subgroup of R-CHOP
      induction studies OR 0.77 (95% CI 0.67-0.88). Serious or grade III/IV adverse
      events including neutropenia and infections were significantly more common in the
      maintenance arm, RR = 1.69 (95% CI 1.29-2.22). MT in patients with DLBCL
      achieving CR or PR after induction therapy did not affect OS, yet it decreased
      relapse rate and improved disease control at the cost of higher infection rate.
      Our data do not support routine administration of MT in patients with DLBCL.

PMID- 30216479
TI  - It is Neither Frankenstein Nor a Submarine Alkaline Vent, It is Just the Second
      Law.

PMID- 30216480
TI  - Evaluation of the developmental toxicity of perfluorooctanesulfonate in the
      Anuran, Silurana tropicalis.
AB  - A 150-day post-metamorphosis (dpm) partial lifecycle study exposing Silurana
      tropicalis to <0.03 (control), 0.06, 0.13 0.25, 0.5 and 1.0 mg/L
      perfluorooctanesulfonate (PFOS) was conducted. A subset of specimens from the
      control and each treatment were evaluated at metamorphic completion. A
      significant increase in the median metamorphosis time was observed in the 1.0
      mg/L PFOS treatment relative to the control. A modest increase in the occurrence,
      but not severity, of mild follicular hypertrophy was found in thyroid glands from
      organisms exposed to the 0.62 and 1.1 mg/L PFOS treatments. At 150 dpm, a
      concentration-dependent increase in whole body PFOS residues was measured ranging
      from 29.6 to 163.5 mg/kg in the 0.05 and 1.1 mg/L PFOS treatments. Decreased body
      weight and snout-vent length were noted in specimens exposed to 1.1 mg PFOS/L at
      the completion of metamorphosis. Body weight was reduced in the 1.1 mg/L PFOS
      concentration; however, snout-vent length was not affected by PFOS exposure at
      150 dpm. An increased proportion of phenotypic males were noted in the 0.62 and
      1.1 mg/L PFOS treatments. Abnormal ovary development characterized by size
      asymmetry, necrosis and formation of excessive fibrous connective tissue was
      identified in females exposed to 0.29 and 1.1 mg PFOS/L. Asymmetrically misshaped
      testes were found at 1.1 mg/L PFOS. Results suggested that PFOS is capable of
      interfering with S. tropicalis growth before metamorphic completion and growth
      and gonad development during juvenile development.

PMID- 30216481
TI  - Review of polyphenol-rich products as potential protective and therapeutic
      factors against cadmium hepatotoxicity.
AB  - Recently, the growing attention of the scientific community has been focused on
      the threat to health created by environmental pollutants, including toxic metals
      such as cadmium (Cd), and on the need of finding effective ways to prevent and
      treat the unfavorable health effects of exposure to them. Particularly promising
      for Cd, and thus arousing the greatest interest, is the possibility of using
      various ingredients present in plants, including mainly polyphenolic compounds.
      As the liver is one of the target organs for this toxic metal and disturbances in
      the proper functioning of this organ have serious consequences for health, the
      aim of the present review was to discuss the possibility of using polyphenol-rich
      food products (e.g., chokeberry, black and green tea, blueberry, olive oil,
      rosemary and ginger) as the strategy in protection from this xenobiotic
      hepatotoxicity and treatment of this heavy metal-induced liver damage. Owing to
      the ability of polyphenols to bind ions of Cd and the strong antioxidative
      potential of these compounds, as well as their abundance in dietary products, it
      seems to be of high importance to consider the possibility of using polyphenols
      as potential preventive and therapeutic agents against Cd hepatotoxicity,
      determined by its strong pro-oxidative properties. Although most of the data on
      the effectiveness of polyphenols comes from studies in animals, the fact that
      some of them are derived from experimental models that reflect human exposure to
      this metal allows us to assume that some polyphenol-rich food products may be
      promising protective agents against Cd hepatotoxicity in humans.

PMID- 30216482
TI  - Stability of reagents used for chiral amino acid analysis during spaceflight
      missions in high-radiation environments.
AB  - The search for biosignatures on spaceflight missions requires in situ
      instrumentation capable of highly selective and sensitive organic analyses. To
      this end, CE-LIF is a uniquely promising technique, capable of determining the
      type, abundance, and chirality of amino acids present in environmental samples at
      nanomolar concentrations. However, this type of assay requires several reagents
      that have not yet been used on spaceflight missions. A key concern, particularly
      for future missions to Europa, is the survivability of these critical components
      for CE separation and LIF detection under high levels of radiation. Here we
      present an investigation of the chemical stability of the reagents and associated
      fused silica capillary after a total ionizing dose of 300 krad, exceeding the
      predicted total ionizing dose for the potential Europa Lander Mission payload by
      two-fold. Neither the fused silica capillary nor the fluorescent dye (5
      carboxyfluorescein succinimidyl ester) showed significant change in performance
      following irradiation. Following the irradiation of the pre-mixed background
      electrolyte, both migration time and resolution were affected. However, when the
      reagents (sodium tetraborate, sodium taurocholate, and gamma-cyclodextrin) and
      the acetonitrile solution were irradiated separately and mixed afterwards, there
      was no change in the separation performance.

PMID- 30216483
TI  - Letter To Editor: Terlipressin is Superior to Noradrenaline in the Management of
      Acute Kidney Injury in Acute On Chronic Liver Failure.

PMID- 30216484
TI  - Oral health-related quality of life and standard of treatment in aggressive
      periodontitis patients more than 5 years after therapy.
AB  - OBJECTIVES: To assess OHRQoL in patients with aggressive periodontitis (AgP)
      after periodontal treatment using the Oral Health Impact Profile-49 (OHIP-49) and
      compare to patients' dental status. MATERIAL AND METHODS: More than 5 years after
      therapy, 71 patients were examined and answered the OHIP-questionnaire. The
      dental and periodontal status were assessed according to the SSO (Swiss Dental
      Society) criteria. Descriptive statistics were performed with SPSS, correlation
      analysis and tests for differences using R 3.2.2. RESULTS: More than 90% of all
      patients showed no probing depths (PD) >5 mm, a bleeding on probing (BOP) index
      below 35%, and a sufficient function. Four patients showed no visible plaque, PDs
      <= 3 mm, a BOP below 10%, and an optimum function. Non-smoking and compliant
      patients exhibited a more favourable status. The OHIP-49 added up to 24.9 points,
      representing a comparatively high satisfaction of AgP-patients with their oral
      status. The subscale which most patients reported impairment in was "functional
      limitation." A correlation between quality standard and the OHIP-49G could only
      be shown in the psychological disability subscale. CONCLUSION: After treatment, a
      moderate to high quality level can be retained over more than 5 years. Most
      patients are satisfied with their oral health. Correlations between the objective
      and subjective view could not be found, apart from the subscale "psychological
      disability."

PMID- 30216485
TI  - Streamlined microfluidic analysis of phosphopeptides using stable isotope-labeled
      synthetic peptides and MRM-MS detection.
AB  - Modern high-throughput and high-content biological research is performed with
      advanced instrumentation and complex and time-consuming protocols, which, as a
      whole, pose a challenge for routine implementation in a research laboratory. In
      support of a "bioanalytical toolbox" with potential utility for exploring
      cellular functions mediated via protein phosphorylation-a post-translational
      modification (PTM) with essential regulatory roles in a variety of cellular
      processes-in this work, we describe the development of a simple, integrated
      microfluidic chip that can perform targeted, quantitative analysis of
      phosphopeptides involved in cancer-relevant signaling pathways. The microfluidic
      device comprises microreactors packed with C18 and TiO2 particles for on-chip
      solid phase extraction (SPE) and phosphopeptide enrichment, and an ESI interface
      for facilitating multiple reaction monitoring (MRM)-mass spectrometry (MS)
      detection. The chips are demonstrated for the detection of three phosphopeptides
      involved in ERBB2/MAPK signaling pathways, selected from the outcome of a
      proteomic study involving EGF stimulation of SKBR3/HER2+ breast cancer cells. The
      data demonstrate that the proposed microfluidic strategy can be used for the MS
      quantification of phosphopeptides in the low nM range from cell lysates without
      any prior sample pretreatment, fractionation or bioaffinity enrichment, and is
      generally applicable to the analysis of any phosphopeptide targets.

PMID- 30216486
TI  - Parasites and allergy: Observations from Africa.
AB  - Population studies from the African continent have observed a marked increase in
      the prevalence of allergy-related diseases over the past few decades, but the
      cause of this rise is not fully understood. The most investigated potential risk
      factor has been the relationship between exposure to helminths and allergy
      related outcomes. Immunologically, parallels exist between responses to helminths
      and to allergens as both are associated with elevated levels of immunoglobulin E,
      increased numbers of T helper 2 cells and other immune cells. However,
      epidemiological studies from the African continent have found inconsistent
      results. In this review, observations from population studies carried out in
      Africa over the last decade that focus on the relationship between helminth
      infections and allergy-related outcomes are examined. How these findings advance
      our understanding of the complex interactions between helminths and allergies at
      the population level is also explored as well as some of the underlying immune
      mechanisms involved. This knowledge is important for better diagnosis, treatment
      and prevention of allergy-related diseases and has wider global significance.

PMID- 30216487
TI  - Necrobiosis lipoidica associated with sarcoidosis.
AB  - We report the case of a 40-year-old African-American female with biopsy-proven
      pulmonary sarcoidosis who developed atrophic plaques on her shins, trunk, and
      scalp that were clinically and histologically consistent with necrobiosis
      lipoidica (NL). The lesions appeared 3 years after her diagnosis of sarcoidosis,
      and progressed despite chronic prednisone. Sarcoidosis and NL are granulomatous
      skin disorders reported to coexist in the same patient only 10 times in the
      literature. Including the current case, patients have been exclusively females
      around middle age, and have greater tendencies to develop typical cutaneous
      sarcoidosis. The incidence of diabetes is rare in this group. Like typical NL, NL
      associated with sarcoidosis tends to ulcerate, and is difficult to treat.
      Interestingly, there are six similar cases reported in the literature of patients
      with sarcoidosis who developed lesions clinically and behaviorally consistent
      with NL, but received a final histological diagnosis of sarcoidosis. These cases
      share very similar demographics and clinical features with cases of true NL
      associated with sarcoidosis, and often have more ambiguous histology containing
      features of both cutaneous sarcoidosis and NL. Comparing the two sets of cases
      raises the possibility of a final common disease pathway shared by these two
      granulomatous skin disorders.

PMID- 30216488
TI  - Combined detection of estrogen and tumor markers is an important reference factor
      in the diagnosis and prognosis of lung cancer.
AB  - The correlation between lung cancer tumor markers and sex differences in lung
      cancer remains a clinical problem that is worthy of further study. This study
      investigated the significance of the combined detection of 17beta-estrogen (E2)
      and tumor markers in the diagnosis and prognosis of lung cancer. A total of 174
      patients, including 117 patients with non-small-cell lung cancer (NSCLC) and 57
      patients with benign pulmonary lesions (BPL), were enrolled. An enzyme-linked
      immunosorbent assay was used to detect the expression of E2, carcinoembryonic
      antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment antigen
      21-1 (CYFRA21-1) in patients with NSCLC and BPL to analyze the correlation
      between E2 and CEA, NSE or CYFRA21-1 expression, and its correlation with
      clinicopathological features and prognosis. The expression of tumor markers was
      then examined in different lung cancer cells (A549, H1795, H460, and SK-MES-1).
      The expression of tumor markers was detected by a real-time reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot analysis. The expressions of
      p-p44/42 mitogen-activated protein kinase (MAPK) and phospho-AKT (p-AKT) were
      detected by Western blot analysis. The expression levels of E2, CEA, NSE, and
      CYFRA21-1 in patients with NSCLC were significantly higher than those in patients
      with BPL ( P < .05); E2 was positively correlated with tumor markers ( P < .01).
      Patients with a high expression of E2 and tumor markers showed a poor prognosis (
      P < .05). RT-quantitative PCR and Western blot analysis showed that the
      expression levels of CEA, NSE, CYFRA21-1, p-p44/42 MAPK, and p-AKT in the E2
      group were higher than those in the other groups ( P < .05). These studies
      indicate that the interaction of E2 and tumor markers can significantly improve
      the role of tumor markers in the diagnosis and prognosis of lung cancer.

PMID- 30216490
TI  - Diversity of Adipose Tissue Immune Cells: Are All Eosinophils Created Equal?

PMID- 30216489
TI  - Lingual amyloidosis associated to long-term hemodialysis: Two case reports.
AB  - The beta2-microglobulin amyloidosis is a newly recognized type of systemic
      amyloidosis, which occurs in patients with chronic renal failure undergoing long
      term hemodialysis. The dialysis-related amyloidosis (DRA) of the tongue is an
      uncommon and late complication, which occurs in patients undergoing chronic
      hemodialysis for more than 20 years. The aim of this paper is to report two cases
      of lingual amyloidosis associated with long-term hemodialysis. Two patients were
      referred to the Oral Medicine Clinic due to the presence of multiple nodules on
      the tongue and macroglossia. The patients had history of chronic renal failure
      and had been dialysed for more 20 years with bio-incompatible cellulose membrane.
      Biopsies of the lesions were performed and the histopathological features and
      Congo red stain revealed oral amyloidosis. Both patients remain in clinical
      follow-up after 12 and 6 months, respectively. Recognition of the amyloidosis
      tongue lesions can minimize the complications caused by this condition such as
      obstruction of the upper airways, making it imperative to carry out early
      treatment. Furthermore, in patients with oral amyloidosis, lesions in areas of
      trauma may ulcerate and cause pain and dysphagia becoming necessary periodic
      surgical removal and regular follow-up of these patients.

PMID- 30216491
TI  - Short-term outcome and risk factors for post-operative complications following
      umbilical resection in 82 foals (2004-2016).
AB  - BACKGROUND: Umbilical remnant infection and patent urachus are an important cause
      of morbidity for the equine neonate. Left untreated, fatal complications can
      develop. Identifying risk factors for post-operative complications after surgery
      are important for estimating prognosis. OBJECTIVES: To identify risk factors
      associated with post-operative complications in foals undergoing umbilical
      remnant resection due to patent and/or infected umbilical remnants. STUDY DESIGN:
      Retrospective case series. METHODS: Foals undergoing umbilical remnant resection
      due to patent urachus or infected remnants at the Marion duPont Scott Equine
      Medical Center from 2004 to 2016 were included in the study. Data were obtained
      from medical records and associations between outcomes and post-operative
      complications, and pre or intraoperative clinical variables were assessed using
      bivariable and multivariable analyses. RESULTS: Eighty-two foals underwent
      umbilical remnant resection of which 73 (89.0%) survived to discharge. The
      urachus was the most commonly affected structure being patent and/or infected in
      84.1% of cases. Concurrent diseases were present in 60.6% of foals prior to
      surgery, with diarrhoea and septic arthritis being most common. The presence of
      preoperative septic arthritis and/or physitis were significantly associated with
      nonsurvival (OR 33; 95% confidence interval 1.1-985.2; P = 0.04). Longer
      anaesthesia time (OR 1.4; 95% confidence interval 1.1-1.7; P = 0.02) and failure
      of passive transfer of immunoglobulins (OR 5.9; 95% confidence interval 1.2
      29.04; P = 0.03) were associated with increased odds for post-operative
      complications. MAIN LIMITATIONS: It is not known if medical treatment alone would
      have been successful in foals that did not receive preoperative medical
      treatment. CONCLUSIONS: Overall survival is high after surgical excision of
      umbilical remnants. The presence of preoperative septic arthritis and/or physitis
      was associated with decreased survival and failure of passive transfer of
      immunoglobulins and longer anaesthesia times were associated with increased odds
      for post-operative complications.

PMID- 30216492
TI  - Oral fluoroquinolones and risk of fibromyalgia.
AB  - The Food and Drug Administration (FDA) has recently included a black box warning
      on fibromyalgia-like symptoms with fluoroquinolones (FQs) but no large
      epidemiologic study is to date available. We undertook a case-control study using
      a random sample of 9 053 240 subjects obtained from the PharMetrics Plus health
      claims database in the United States. Cases received at least two fibromyalgia
      diagnoses coded by a rheumatologist matched to ten randomly selected controls.
      After identifying 5148 cases of fibromyalgia and 51 480 controls, the adjusted
      rate ratio (RR) of fibromyalgia for use of any fluoroquinolones, amoxicillin and
      azithromycin were 1.63 (95% CI: 1.41-1.87), 1.64 (95% CI: 1.46-1.85) and 1.68
      (95% CI, 1.49-1.89), respectively. The adjusted RR for any use of FQ compared to
      any use of amoxicillin or azithromycin was 0.99 (95% CI: 0.83-1.18) and
      azithromycin is 0.97 (95%CI: 0.82-1.16), respectively. The risk of fibromyalgia
      with FQs is similar to that with amoxicillin and azithromycin.

PMID- 30216493
TI  - Upregulated microRNA-132 rescues cardiac fibrosis and restores cardiocyte
      proliferation in dilated cardiomyopathy through the phosphatase and tensin
      homolog-mediated PI3K/Akt signal transduction pathway.
AB  - Cardiac fibrosis is known to be present in dilated cardiomyopathy (DCM) and it
      predicts the occurrence of sudden death and congestive heart failure. The aim of
      our study is to investigate the expression of microRNA-132 (miR-132) and its
      effect on cardiocyte proliferation, apoptosis, and cardiac fibrosis by binding to
      phosphatase and tensin homolog (PTEN) through the phosphateidylinositol 3-kinase
      (PI3K)/protein kinase (Akt) signal transduction pathway in DCM rats. DCM rat
      models induced by doxorubicin were established and confirmed by an ultrasonic
      cardiogram. Epithelial cells were treated with inhibitors, activators, and small
      interfering RNAs to identify the mechanisms by which miR-132 controls cardiocyte
      activity and cardiac fibrosis. Angiotensin II (Ang II) and aldosterone (ALD)
      expressions were detected by an enzyme-linked immunosorbent assay. The
      relationship between PTEN and miR-132 was verified by a dual-luciferase reporter
      assay. Cell proliferation and apoptosis were tested by the MTT assay and flow
      cytometry. PTEN was determined to be the target gene of miR-132. Rat models of
      DCM exhibited a lower level of miR-132, PI3K, Akt, B-cell lymphoma 2, collagen I,
      and collagen III, but a higher level of PTEN, Bcl-2-associated X protein, and
      proliferating cell nuclear antigen as well as inflammatory response (Ang II and
      ALD), accompanied by declined cardiocyte proliferation and elevated apoptosis and
      cardiac fibrosis. Upregulated miR-132 or silenced PTEN activated the PI3K/Akt
      pathway, thus facilitating cardiocyte proliferation and repressing cardiocyte
      apoptosis and cardiac fibrosis, as well as inflammatory responses. Downregulated
      miR-132 reversed this tendency. These findings indicate that miR-132 activates
      the PI3K/Akt pathway by inhibiting PTEN expression, thus facilitating cardiocyte
      proliferation and inhibiting apoptosis and cardiac fibrosis in DCM rats.

PMID- 30216494
TI  - Serum fatty acid-binding protein 4 level is inversely correlated with serum
      thymus and activation-regulated chemokine level in psoriatic patients achieving
      clear skin by biologics.

PMID- 30216495
TI  - Dengue fever is an emerging public health concern in the city of Multan,
      Pakistan: its seroprevalence and associated risk factors.
AB  - The prevalence of dengue IgG and IgM antibodies was investigated in 689 patients
      with suspected dengue. Of the 689 suspected cases, 373 (54.1%) were found to be
      positive for dengue antibodies, IgM being dominant. There was a significant
      relationship between incidence of dengue fever and season: all cases were
      reported during the rainy season, especially the post-monsoon season (89.5%),
      with none during the dry season. More male (79.3%) than female individuals were
      positive cases and the incidence was highest in the 21-49 year age group (63%).
      This is the first seroprevalence study reported from Multan, Pakistan.

PMID- 30216496
TI  - Paraneoplastic pemphigus presenting lichen planus-like lesions.

PMID- 30216497
TI  - Red nucleus interleukin-1beta evokes tactile allodynia through activation of
      JAK/STAT3 and JNK signaling pathways.
AB  - We previously reported that interleukin-1beta (IL-1beta) in the red nucleus (RN)
      is involved in pain modulation and exerts a facilitatory effect in the
      development of neuropathic pain. Here, we explored the actions of signaling
      pathways, including the Janus kinase/signal transducer and activator of
      transcription 3 (JAK/STAT3), c-Jun N-terminal kinase (JNK), extracellular signal
      regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and
      nuclear factor-kappaB (NF-kappaB) pathways, on RN IL-1beta-mediated pain
      modulation. After a single dose of recombinant rat IL-1beta (rrIL-1beta, 10 ng)
      injected into the RN in normal rats, a tactile allodynia was evoked in the
      contralateral but not ipsilateral hindpaw, commencing 75 min and peaking 120 min
      postinjection. Up-regulated protein levels of phospho-STAT3 (p-STAT3) and p-JNK
      were observed in the RN 120 min after rrIL-1beta injection, the increases of p
      STAT3 and p-JNK were blocked by anti-IL-1beta antibody. However, the expression
      levels of p-ERK, p-p38 MAPK, and NF-kappaB in the RN were not affected by rrIL
      1beta injection. RN neurons and astrocytes contributed to IL-1beta-evoked up
      regulation of p-STAT3 and p-JNK. Further studies demonstrated that injection of
      the JAK2 antagonist AG490 or JNK antagonist SP600125 into the RN 30 min prior to
      the administration of rrIL-1beta could completely prevent IL-1beta-evoked tactile
      allodynia, while injection of the ERK antagonist PD98059, p38 MAPK antagonist
      SB203580, or NF-kappaB antagonist PDTC did not affect IL-1beta-evoked tactile
      allodynia. In conclusion, our data provide additional evidence that RN IL-1beta
      is involved in pain modulation, and that it exerts a facilitatory effect by
      activating the JAK/STAT3 and JNK signaling pathways.

PMID- 30216498
TI  - Searching for biomarkers of chronic obstructive pulmonary disease using
      proteomics: The current state.
AB  - Detection of proteins which may be potential biomarkers of disorders represents a
      big step forward in understanding the molecular mechanisms that underlie
      pathological processes. In this context proteomics plays the important role of
      opening a path for the identification of molecular signatures that can
      potentially assist in early diagnosis of several clinical disturbances. Aim of
      this report is to provide an overview of the wide variety of proteomic strategies
      that have been applied to the investigation of chronic obstructive pulmonary
      disease (COPD), a severe disorder that causes an irreversible damage to the lungs
      and for which there is no cure yet. The results in this area published over the
      past decade show that proteomics indeed has the ability of monitoring alterations
      in expression profiles of proteins from fluids/tissues of patients affected by
      COPD and healthy controls. However, these data also suggest that proteomics,
      while being an attractive tool for the identification of novel pathological
      mediators of COPD, remains a technique mainly generated and developed in research
      laboratories. Great efforts dedicated to the validation of these biological
      signatures will result in the proof of their clinical utility.

PMID- 30216499
TI  - Successful outcome of early ambulation after extensive skin grafting in
      extramammary Paget's disease.
AB  - Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that mainly
      affects the senior population. There is a relatively high risk of postoperative
      complications from surgery in the senior population, such as disuse syndrome,
      deep vein thrombosis and postoperative delirium. To prevent such postoperative
      complications, early ambulation is recommended. However, EMPD often requires
      extensive skin grafting because of the need for a large resection margin. To
      avoid skin graft failure, many institutions require that patients have several
      days of postoperative bedrest. For these reasons, there has been no consensus on
      standard postoperative rest for EMPD. In this study, we defined 20 patients who
      walked from the day after surgery as an "early ambulation group" and 23 patients
      with 5 days postoperative bedrest as a "control group". We evaluated the skin
      graft survival, postoperative complications and the duration of hospitalization
      for both groups. Skin graft survival and complications related to the surgical
      wounds (infection and hemorrhage) in the early ambulation group were found to be
      comparable with those in the control group. Of note, the other complications
      (aspiration pneumonia, ileus, delirium, orthostatic hypotension and insomnia)
      were less frequent (P < 0.001) and the duration of postoperative hospitalization
      was shorter (P = 0.013) in the early ambulation group than in the control group.
      Our study suggests that early ambulation after surgery for EMPD does not impair
      skin graft survival but reduces postoperative complications and the duration of
      hospitalization.

PMID- 30216500
TI  - The long noncoding RNA HIF1A-AS2 facilitates cisplatin resistance in bladder
      cancer.
AB  - Chemotherapy drug resistance frequently happens in more than 50% of bladder
      cancer patients and is the major obstacle for the bladder cancer therapy. Recent
      studies have shown that long noncoding RNA (lncRNA) is involved in the
      development of chemoresistance. In this study, we reported hypoxia inducible
      factor 1alpha-antisense RNA 2 (HIF1A-AS2), as a subtype-specific hypoxia
      inducible lncRNA, is upregulated in bladder cancer cells and tissue after
      cisplatin (Cis) treatment. The induction of HIF1A-AS2 in bladder cancer cells
      rendered resistance to Cis-induced apoptosis. Silencing HIF1A-AS2 in Cis
      resistant bladder cancer cells was re-sensitized to Cis-induced apoptosis.
      Mechanically, we found that HIF1A-AS2 suppressed the transcription activity of
      p53 family proteins by promoting the expression of high-mobility group A1
      (HMGA1). The induction of HMGA1 physically interacts with p53, p63, and p73, and
      therefore constrains their transcriptional activity on Bax. Knockdown of HIF1A
      AS2 or HMGA1 rescued the expression of Bax, which therefore enhanced the killing
      effect of Cis. Furthermore, we also found that the expression of HIF1A-AS2 was
      higher in the human bladder tumor tissues after Cis treatment, and was positive
      correlated to the expression of HIF1alpha and HMGA1. This study suggests that
      upregulated HIF1A-AS2 hampers the p53 family proteins dependent apoptotic pathway
      to promote Cis resistance in bladder cancer. Our data suggested that HIF1A-AS2
      plays oncogenic roles and can be used as a therapeutic target for treating human
      bladder cancer.

PMID- 30216501
TI  - FOXO1 associated with sensitivity to chemotherapy drugs and glial-mesenchymal
      transition in glioma.
AB  - Mesenchymal subtype of glioblastoma (GBM), identified as one of four clinically
      relevant molecular subtypes, has worst prognosis because of its close relation
      with the malignant biological properties induced by glial-mesenchymal transition
      (GMT). However, the molecular mechanism of GMT and its characterized molecule of
      GBM have not been studied. Forkhead box protein O1 (FOXO1) is at a convergence
      point of receptor tyrosine kinase signaling as one of the three core pathways
      implicated in GBM. Our previous study indicated that the inactivation of FOXO1
      involved in the inhibition of GMT is an independent prognosis factor of GBM. In
      this study, we will further confirm the role of FOXO1 in GMT through cytological
      experiments to clarify how FOXO1 regulates GMT and its clinical significance. We
      established virus-infected FOXO1 overexpression and FOXO1 knockdown cells of U373
      MG and U251 mediated by lentivirus, based on the effect of which FOXO1-correlated
      GMT experiments were performed in vitro and in vivo. Our data suggested that
      FOXO1 played a crucial role in resistance to TMZ, BCNU, and CDDP; migration and
      invasion; and stem cell properties of glioma cells. FOXO1 may serve as a targeted
      biomarker for prediction of sensitivity to chemotherapy drugs, metastasis, and
      prognosis, which provides a new idea for mesenchymal GBM treatment.

PMID- 30216502
TI  - ROS-challenged keratinocytes as a new model for oxidative stress-mediated skin
      diseases.
AB  - In the current study, the effects of the reactive oxygen species (ROS) generator
      2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) on extracellular and
      intracellular ROS production in human keratinocytes (HACAT) were studied. AAPH is
      a water-soluble compound able to generate ROS at known and constant rates at 37
      degrees C. The short treatment (2 h) with AAPH brought a significant dose
      dependent increase in NADPH oxidase activity in intact keratinocytes. The long
      term treatment (24 h) with AAPH led to a persistent increase in NADPH oxidase
      activity for up to 48 hour following the AAPH removal from cell incubation
      medium. ROS and nitric oxide levels, lipoperoxidation, intracellular calcium,
      mitochondrial superoxide production, and membrane potential were significantly
      modified in AAPH-treated HACAT. Superoxide dismutase (SOD) and/or catalase
      addition to HACAT revealed that untreated keratinocytes produce mostly superoxide
      anion (O 2 - ), while AAPH-treated keratinocytes overproduce hydrogen peroxide (H
      2 O 2 ) in extracellular medium. H 2 O 2 is particularly stable and plays
      important roles in several cell signaling pathways. Taken together, our findings
      suggest a cost-effective and easily reproducible in vitro model of stressed human
      keratinocytes releasing significantly elevated ROS amounts in extracellular
      medium with respect to control keratinocytes. The possible application of the
      proposed model for keratinocytes-melanocytes cross-talk studies is also
      suggested. The model of AAPH-stressed human keratinocytes described here can
      represent a useful tool for redox cross-talk studies between keratinocytes and
      other skin cell types, and applied for researches regarding skin pathologies
      associated with oxidative stress.

PMID- 30216503
TI  - The Dissipative Potential of Gamma Irradiation in Residues of Imidacloprid and
      Thiamethoxam in the Postharvest of Common Beans.
AB  - : Gamma irradiation (60 Co) in postharvest of common beans (Phaseolus vulgaris
      L.), has already proven beneficial, regarding the prolongation of shelf life and
      physical, chemical, and organoleptic aspects of grains. However, few prior
      studies have investigated the effect of gamma irradiation on the dissipation of
      pesticides in foods, especially insecticides in beans. This study aimed to
      evaluate the waste dissipation of two insecticides, imidacloprid and
      thiamethoxam, used in the cultivation of common bean, a variety of Carioca, using
      gamma irradiation. Ground bean samples were spiked each insecticide in the
      laboratory at 3, 4, and 5 mg/kg, and were then irradiated at 0, 1, and 2 kGy per
      irradiator with a 60 Co source. Liquid chromatography-tandem mass spectrometry
      was used to quantify the insecticides. The irradiation promoted dissipation of
      thiamethoxam at 1 and 2 kGy doses, with the highest dissipation verified at 2
      kGy. In general, at this higher dose of irradiation the reduction dissipation of
      thiamethoxam was 66% of the mean value found in the treatment without irradiation
      and ~44% relative to the 1 kGy dose. Conversely, imidacloprid showed no effect of
      irradiation on waste dissipation, except in the treatment of 5 mg/kg at 2 kGy
      dose. From the results, it was concluded that the gamma irradiation might have
      applicability in dissipating thiamethoxam in real bean samples. PRACTICAL
      APPLICATION: Pesticide residues remaining from bean cultivation, sensitive to
      optimal doses of gamma irradiation, can be transformed into other less harmful or
      nonharmful substances, increasing the quality of the beans before the food
      arrives at the consumer's table. Irradiation of the grains after harvest also
      eliminates the need for application of other pesticides to preserve the grains
      during storage, as the technique is capable of eradicating deteriorating agents,
      such as microorganisms and insects.

PMID- 30216504
TI  - Autophagy in osteoporosis: Relation to oxidative stress.
AB  - Impaired autophagy and oxidative stress are implicated in the development of many
      diseases. This study aimed to investigate the involvement of autophagy
      represented by autophagy-related gene 7 (Atg7) and oxidative stress represented
      by superoxide dismutase 2 (SOD2) gene expression and enzyme activity in the
      pathogenesis of osteoporosis. Atg7 and SOD2 gene relative expression were
      evaluated by SYBR green quantitative real-time-polymerase chain reaction in the
      osteoporotic group (n = 26) versus the osteoporosis free group (n = 14). SOD2
      enzyme activity was evaluated by colorimetric method in both study groups. Both
      Atg7 and SOD2 relative expression showed highly significant decrease (P < 0.01)
      between both groups. However, SOD2 enzyme activity showed no significant
      difference between the two groups. There was a significant direct correlation
      between Atg7 and SOD2 gene expression in both study groups. Atg7 relative
      expression showed significant ( P < 0.01) direct correlation with vitamin D serum
      levels and body mass index in osteoporotic group. In conclusion, both genes are
      involved in the pathogenesis of osteoporosis and this could be amenable to future
      therapeutic intervention.

PMID- 30216505
TI  - Effects of miR-503-5p on apoptosis of human pulmonary microvascular endothelial
      cells in simulated microgravity.
AB  - Recent studies have shown that microRNA (miRNAs) can play important roles in the
      regulation of endothelial cell (EC) function. However, the expression profile of
      miRNAs and their effects on the apoptosis of ECs under microgravity conditions
      remains unclear. In this study, the apoptosis of human pulmonary microvascular
      endothelial cells (HPMECs) under simulated microgravity was identified by Annexin
      V and propidium iodide double staining and transmission electron microscopy.
      miRNA microarray assay was used to screen the differentially expressed miRNAs in
      HPMECs under simulated microgravity, and eight differentially expressed miRNAs
      were identified. Specifically, miR-503-5p, which was found to be most
      significantly upregulated in both microarray and quantitative reverse
      transcription polymerase chain reaction assays, was selected for further
      functional investigation. Overexpression of miR-503-5p induced apoptosis of
      HPMECs under normal gravity and aggravated the negative effects of simulated
      microgravity on HPMECs. Furthermore, silencing of miR-503-5p expression
      effectively attenuated the negative effects of simulated microgravity on HPMECs.
      Further experiments showed that the mRNA and protein expression of anti-apoptotic
      factor B-cell lymphoma-2 (Bcl-2), which has been confirmed as a direct target of
      miR-503-5p, was inhibited by the upregulation of miR-503-5p and increased by the
      downregulation of miR-503-5p. Taken together, our findings demonstrate, for the
      first time, that miR-503-5p can induce apoptosis of HPMECs under simulated
      microgravity through, at least in part, inhibiting the expression of Bcl-2.

PMID- 30216507
TI  - Transduction and transfection of difficult-to-transfect cells: Systematic
      attempts for the transfection of protozoa Leishmania.
AB  - Cell-penetrating peptides (CPPs) are used to internalize different cargoes,
      including DNA, into live mammalian and plant cells. Despite many cells being
      easily transfected with this approach, other cells are rather "difficult" or
      "hard to transfect," including protist cells of the genus Leishmania. Based on
      our previous results in successfully internalizing proteins into Leishmania
      tarentolae cells, we used single CPPs and three different DNA-binding proteins to
      form protein-like complexes with plasmids covered with CPPs. We attempted
      magnetofection, electroporation, and transfection using a number of commercially
      available detergents. While complex formation with negatively charged DNA
      required substantially higher amounts of CPPs than those necessary for mostly
      neutral proteins, the cytotoxicity of the required amounts of CPPs and
      auxiliaries was thoroughly studied. We found that Leishmania cells were indeed
      susceptible to high concentrations of some CPPs and auxiliaries, although in a
      different manner compared with that for mammalian cells. The lack of successful
      transfections implies the necessity to accept certain general limitations
      regarding DNA internalization into difficult-to-transfect cells. Only
      electroporation allowed reproducible internalization of large and rigid plasmid
      DNA molecules through electrically disturbed extended membrane areas, known as
      permeable membrane macrodomains.

PMID- 30216506
TI  - Peroxisome proliferator-activated receptor gamma coactivator-1alpha/HSF1 axis
      effectively alleviates lipopolysaccharide-induced acute lung injury via
      suppressing oxidative stress and inflammatory response.
AB  - Acute lung injury (ALI) interferes with lung function by causing pulmonary
      inflammation and oxidative stress. Suppressing intracellular reactive oxygen
      species (ROS) may block intracellular inflammation. Thus, the purpose of the
      current study was to investigate the roles of peroxisome proliferator-activated
      receptor gamma coactivator-1alpha (PGC1alpha)/HSF1 axis in an lipopolysaccharide
      (LPS)-induced ALI murine model and in RAW264.7 macrophages. In the LPS
      administrated mouse model, the addition of PGC1alpha obviously ameliorated
      secretion of pro-inflammatory mediators tumor necrosis factor-alpha and
      Interleukin 6 as well as MCP-1 expression triggered by LPS stimulation,
      accompanied with reduced infiltration of inflammatory cells. Meanwhile,
      introduction of PGC1alpha strongly diminished the expression of cyclooxygenase-2
      and inducible nitric oxide synthase as well as their products PGE2 and NO. In
      addition, administering PGC1alpha also dramatically alleviated LPS-triggered
      oxidative stress, as reflected by a reduction of ROS production, and also reduced
      malondialdehyde and O 2 content, concomitant with enhancement of superoxide
      dismutase, catalase, and glutathione peroxidase. Similarly, PGC1alpha effectively
      ameliorated LPS-induced inflammation response and oxidative stress, as
      exemplified by reduced pro-inflammatory cytokines and ROS production in LPS
      induced RAW264.7 macrophages. Interestingly, PGC1alpha modulated the expression
      of HSF1 and the transcriptional activity of X-linked inhibitor of apoptosis
      (XIAP)-associated factor 1, whereas silencing of HSF1 abolished these effects.
      More importantly, deletion of HSF1 impeded the anti-inflammatory and anti-oxidant
      effects of PGC1alpha in LPS-induced macrophages. Taken together, PGC1alpha/HSF1
      axis have an anti-oxidant and anti-inflammatory effects, indicating that
      PGC1alpha/HSF1 may protect against LPS-induced ALI, and thus may be a promising
      therapy to treat ALI.

PMID- 30216508
TI  - What we measure ... and what we should measure in medical education.
AB  - CONTEXT: As the practice of medicine evolves, the knowledge, skills and attitudes
      required to provide patient care will continue to change. These competency-based
      changes will necessitate the restructuring of assessment systems. High-quality
      assessment programmes are needed to fulfil health professions education's
      contract with society. OBJECTIVES: We discuss several issues that are important
      to consider when developing assessments in health professions education. We
      organise the discussion along the continuum of medical education, outlining the
      tension between what has been deemed important to measure and what should be
      measured. We also attempt to alleviate some of the apprehension associated with
      measuring evolving competencies by discussing how emerging technologies,
      including simulation and artificial intelligence, can play a role. METHODS: We
      focus our thoughts on the assessment of competencies that, at least historically,
      have been difficult to measure. We highlight several assessment challenges,
      discuss some of the important issues concerning the validity of assessment
      scores, and argue that medical educators must do a better job of justifying their
      use of specific assessment strategies. DISCUSSION: As in most professions, there
      are clear tensions in medicine in relation to what should be assessed, who should
      be responsible for administering assessment content, and how much evidence should
      be gathered to support the evaluation process. Although there have been advances
      in assessment practices, there is still room for improvement. From the student's,
      resident's and practising physician's perspectives, assessments need to be
      relevant. Knowledge is certainly required, but there are other qualities and
      attributes that are important, and perhaps far more important. Research efforts
      spent now on delineating what makes a good physician, and on aligning new and
      upcoming assessment tools with the relevant competencies, will ensure that
      assessment practices, whether aimed at establishing competence or at fostering
      learning, are effective with respect to their primary goal: to produce qualified
      physicians.

PMID- 30216509
TI  - High levels of methionine and methionine sulfoxide: Impact on adenine nucleotide
      hydrolysis and redox status in platelets and serum of young rats.
AB  - We investigated acute and chronic effects administration of methionine (Met)
      and/or methionine sulfoxide (MetO) on ectonucleotidases and oxidative stress in
      platelets and serum of young rats. Wistar rats were divided into four groups:
      control, Met, MetO, and Met + MetO. In acute treatment, the animals received a
      single subcutaneous injection of amino acid(s) and were euthanized after 1 and 3
      hours. In chronic protocol, Met and/or MetO were administered twice a day with an
      8-hour interval from the 6th to the 28th day of life. Nucleoside triphosphate
      phosphohydrolase and 5'-nucleotidase activities were reduced in platelets and
      serum by Met, MetO, and Met + MetO after 3 hours and 21 days. Adenosine deaminase
      activity reduced in platelets at 3 hours after MetO and Met + MetO administration
      and increased after 21 days in animals treated with Met + MetO. Superoxide
      dismutase and catalase activities decreased in platelets in MetO and Met + MetO
      groups after 3 hours, while reactive oxygen species (ROS) levels increased in
      same groups. Catalase activity in platelets decreased in all experimental groups
      after chronic treatment. Met, MetO, and Met + MetO administration increased
      plasmatic ROS levels in acute and chronic protocols; glutathione S-transferase
      activity increased by MetO and Met + MetO administration at 3 hours, and ascorbic
      acid decreased in all experimental groups in acute and chronic protocols.
      Thiobarbituric acid reactive substances increased, superoxide dismutase and
      catalase activities reduced in the Met and/or MetO groups at 3 hours and in
      chronic treatment. Our data demonstrated that Met and/or MetO induced changes in
      adenine nucleotide hydrolysis and redox status of platelets and serum, which can
      be associated with platelet dysfunction in hypermethioninemia.

PMID- 30216510
TI  - microRNA-542-5p protects against acute lung injury in mice with severe acute
      pancreatitis by suppressing the mitogen-activated protein kinase signaling
      pathway through the negative regulation of P21-activated kinase 1.
AB  - Severe acute pancreatitis (SAP) is a condition associated with high rates of
      mortality and lengthy hospital stays. In the current study, SAP mouse models were
      established in BALB/c wild-type and P21-activated kinase 1 (PAK1) knockdown mice
      with the objective of determining the expression of microRNA-542-5p (miR-542-5p)
      and the subsequent elucidation of the mechanism by which it influences acute lung
      injury (ALI) by mediating mitogen-activated protein kinase (MAPK) signaling and
      binding to PAK1. The targeting relationship between miR-542-5p and PAK1 was
      verified using the bioinformatics prediction website and by the means of a dual
      luciferase reporter assay. Following the SAP model establishment, the mice were
      assigned into various groups with the introduction of different mimic and
      inhibitors in an attempt to investigate the effects involved with miR-542-5p on
      inflammatory reactions among mice with SAP-associated ALI. Our results indicated
      that PAK1 was targeted and negatively mediated by miR-542-5p. Mice with SAP
      associated ALI exhibited an increased wet-to-dry weight ratio, myeloperoxidase
      activity, serum amylase activity, TNF-alpha, interleukin-1 beta (IL-1beta), and
      intercellular adhesion molecule-1 (ICAM-1) contents, p-p38MAPK, p-ERK1/2, and p
      JNK protein levels as well as PAK1 positive expression, while decreased miR-542
      5p levels were observed. Functionally, overexpression of miR-542-5p improves ALI
      in mice with SAP via inhibition of the MAPK signaling pathway by binding to
      PAK1.Based on the evidence from experimental models, miR-542-5p was shown to
      improve ALI among mice with SAP, while suggesting that the effect may be related
      to the inactivation of the MAPK signaling pathway and downregulation of PAK1
      gene. Thus, miR-542-5p could serve as a promising target for ALI treatment.

PMID- 30216511
TI  - Let-7g inhibits synthesis of estradiol by downregulating activity of aromatase in
      JEG3 cells.
AB  - BACKGROUND: Increased production of estrogen in human placenta during pregnancy
      closely associates with parturition. Aromatase, encoded by CYP19A1 gene, is an
      enzyme critical for biosynthesis of estrogen. Despite numerous efforts in the
      past few decades ascribed to characterizing the mechanisms of transcriptional
      control of aromatase, the posttranscriptional control of CYP19A1 remains poorly
      understood. OBJECTIVE: In this study, we sought to investigate the role of
      microRNA, let-7g, in posttranscriptional regulation of aromatase in human
      trophoblast choriocarcinoma cell line, JEG3. METHODS AND RESULTS: We show that
      the expression of let-7g was downregulated in JEG3 cell line, but upregulated in
      primary term trophoblast; conversely, aromatase was upregulated in JEG3 but
      downregulated in primary trophoblast. We further show that let-7g antagomirs and
      mimics increased and decreased aromatase expression, respectively; and let-7g
      directly targeted 3'-untranslated region of CYP19A1 mRNA by using dual luciferase
      assay. Using ELISA, we also demonstrate that let-7g antagomirs and mimics
      robustly increased and decreased production of estradiol, respectively.
      DISCUSSION: Our results suggest that aromatase expression is regulated at
      multiple molecular layers in the placenta. These results further suggest that
      JEG3 cell line is a valuable tool to study additional mechanisms associated with
      human birth.

PMID- 30216512
TI  - Knockdown of RPL34 inhibits the proliferation and migration of glioma cells
      through the inactivation of JAK/STAT3 signaling pathway.
AB  - Ribosomal protein L34 (RPL34), belonging to the L34E family of ribosomal
      proteins, was reported to be dysregulated in several types of cancers and plays
      important roles in tumor progression. However, the expression and roles of RPL34
      in human glioma remain largely unknown. Thus, the objective of this study was to
      investigate the expression and role of RPL34 in glioma. We report here that RPL34
      is highly expressed in human glioma tissues and cell lines. Knockdown of RPL34
      markedly inhibited the proliferation, migration, and invasion, as well as
      prevented the epithelial-mesenchymal transition phenotype in glioma cells.
      Further, mechanistic analysis showed that knockdown of RPL34 significantly
      downregulated the levels of p-JAK and p-STAT3 in glioma cells. Taken together,
      our findings indicated that knockdown of RPL34 inhibits the proliferation and
      migration of glioma cells through the inactivation of JAK/STAT3 signaling
      pathway. Thus, RPL34 may serve as a potential therapeutic target for the
      treatment of glioma.

PMID- 30216513
TI  - Interaction of estrogen receptor beta5 and interleukin 6 receptor in the
      progression of non-small cell lung cancer.
AB  - Numerous studies have shown that the estrogen receptor beta (ERbeta) and
      interleukin 6 receptor (IL-6R) had interaction in many tumors, including lung
      cancer. Previous studies found that ERbeta5 exhibits a different biological
      function compared with the other subtypes of ERbeta. Therefore, this study mainly
      explores the interaction between ERbeta5 and IL-6R in the progression of lung
      cancer. We found that the expression of ERbeta5, IL-6 and glycoprotein 130
      (GP130) were significantly increased (P < 0.001) and the 5-year survival rate
      with the co-expression of ERbeta5 and GP130 is significantly lower (P = 0.0315)
      in non-small cell lung cancer (NSCLC) patients. The cell proliferation, invasion,
      and cell cycle were markedly increased, and the cell apoptotic was markedly
      inhibited with the concurrent action of ERbeta5 and IL-6 in A549 cells (P <
      0.05). In addition, the expression of ERbeta5, GP130, p-AKT, and p-44/42 MAPK was
      also significantly increased in A549 cells (P < 0.05). These results indicate
      that ERbeta5 and GP130 can synergistically promote the progression of NSCLC and
      maybe combined as an independent prognostic factor in patients. In addition,
      these results also provide a theoretical basis for the combined targeting therapy
      of ERbeta5 and GP130 in NSCLC.

PMID- 30216514
TI  - Tangeretin inhibits streptozotocin-induced cell apoptosis via regulating NF
      kappaB pathway in INS-1 cells.
AB  - Oxidative stress is considered to play an important role in inducing the
      pancreatic beta-cells apoptosis and promoting the development of diabetes
      mellitus. Tangeretin is a plant-derived flavonoid that retains antidiabetic
      effects. However, the role of tangeretin in streptozotocin (STZ)-induced beta
      cell apoptosis remains unclear. In this study, we aimed to examine the effects of
      tangeretin on STZ-induced cell apoptosis and the underlying mechanisms implicated
      in vitro. Our results showed that tangeretin improved the cell viability in STZ
      induced INS-1 cells. Tangeretin reduced the increase of apoptosis ratio and
      revered the altered expressions of Bax and Bcl-2 caused by STZ induction.
      Furthermore, the impairment of insulin secretion ability as well as a reduction
      in messenger RNA levels of insulin 1 and 2 was significantly attenuated by
      tangeretin in STZ-induced INS-1 cells. Moreover, tangeretin resulted in a
      significant decrease in reactive oxygen species content, accompanied by an
      evident increase in the activities of superoxide dismutase, catalase, and
      glutathione peroxidase. Mechanistic studies further revealed that tangeretin
      inhibited the NF-kappaB pathway in STZ-induced INS-1 cells. These data indicated
      that tangeretin improved the cell apoptosis induced by STZ in INS-1 cells, which
      might be partly due to its antioxidant potential. Furthermore, NF-kappaB was
      found to be involved in the protective effect of tangeretin. Collectively, the
      results indicated that tangeretin could be used as a therapeutic approach for
      diabetes mellitus treatment.

PMID- 30216515
TI  - Novel TGF-beta1 inhibitor antagonizes TGF-beta1-induced epithelial-mesenchymal
      transition in human A549 lung cancer cells.
AB  - Transforming growth factor beta1 (TGF-beta1), a multifunctional cytokine, is
      known to promote tumor invasion and metastasis and induce epithelial-mesenchymal
      transition (EMT) in various cancer cells. Inhibition of TGF-beta1 signaling is a
      new strategy for cancer therapy. Most cancer cells display altered or
      nonfunctional TGF-beta1 signaling; hence, TGF-beta1 inhibitors exert limited
      effects on these cells. Recent studies have suggested that developing a TGF-beta1
      inhibitor from natural compounds is a key step to create novel therapeutic
      agents. This study aimed to develop a new anti-TGF-beta1 therapy for cancer. We
      found an improved analog of chalcones, compound 67, and investigated its effects
      in vitro. We demonstrated the inhibitory role of compound 67 through migration
      and invasion assays on TGF-beta1-induced EMT of human A549 lung cancer cells.
      Compound 67 inhibited TGF-beta1-induced smad2 phosphorylation, suppressed TGF
      beta1-induced EMT markers, matrix metalloproteinase-2 (MMP-2) and MMP-9, and
      inhibited migration and invasion of A549 cells. The study results showed that
      compound 67 is useful to prevent tumor growth and metastasis.

PMID- 30216516
TI  - The incidence of pediatric malignant soft tissue tumors of the skin and
      subcutaneous tissue.
AB  - Soft tissue tumors are a known, albeit uncommon, cause of cutaneous malignancy in
      children. Little is known about which types and how frequently these tumors
      initially present in the skin or subcutis of children. Using data from the 2000
      2014 SEER-18 database, we have identified 12 malignant soft tissue tumor types,
      which initially presented in the skin or subcutis of children in over 50% of
      cases.

PMID- 30216517
TI  - The sphingosine 1-phosphate receptor agonist FTY720 interfered the distribution
      of dendritic cell and induced the maternal-fetal immune tolerance.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of FTY720, an
      agonist of the sphingosine 1-phosphate (S1P) receptor, on the embryo loss rate in
      mice of spontaneous abortion model and the underlying mechanism. METHODS: The
      effect of intraperitoneal injection of FTY720 on the embryo loss rate in mice of
      spontaneous abortion model was observed. The expression of S1PR on the dendritic
      cell (DC) surface was detected by reverse transcription polymerase chain
      reaction. The quantity and maturation of DCs in peripheral blood and local
      tissues of pregnant mice, and the expression of CCL19 as well as its receptor C-C
      chemokine receptor 7 (CCR7) were detected by flow cytometry and
      immunohistochemistry. Chemotaxis assay was performed to verify the effect of
      FTY720 on the chemotaxis of DCs. RESULTS: (1) FTY720 had no significant effect on
      the embryo loss rate in normal pregnant rats. In contrast, adoptive transferring
      of FTY720 significantly reduced the embryo loss rate of the spontaneous abortion
      mouse model (P < 0.05). (2) S1PR was extensively expressed on DC surface. The S1P
      receptor agonist FTY720 reduced the expressions of DC surface chemokines and its
      receptor (P < 0.05), resulting in a significant reduction in the number of DCs
      that were chemoattracted to maternal-fetal interface flow cytometry (P < 0.05).
      (3) FTY720 had no significant effect on the differentiation and apoptosis rate of
      DCs (P > 0.05). CONCLUSION: We hypothesized that FTY720 may reduce the number of
      DCs that were chemoattracted to the maternal-fetal interface by downregulating
      the expression of CCR7, which ultimately induces maternal-fetal immune tolerance.

PMID- 30216518
TI  - Interleukin 17 is an important pathogenicity gene in pediatric sepsis.
AB  - OBJECTIVE: Sepsis represents a complex disease with the dysregulated inflammatory
      response. The purpose of this study is to explore the role of interleukin 17 (IL
      17, also known as IL-17A) in the occurrence and development of pediatric sepsis.
      METHODS: We established the sepsis neonatal rat model with the method of
      intraperitoneal injection of Escherichia coli (E coli). At each target time
      point, we got the blood from heart after anesthetizing animals, and the lung and
      liver tissues were fixed in formalin. Immunohistochemistry and enzyme-linked
      immunosorbent assay assay was used to analyze the expression of IL-17A in the
      lung/liver and plasma respectively. A public data set of neonatal sepsis gene
      microarray was used to verify our result, and explore main functions of IL-17A in
      sepsis. RESULTS: The expression levels of IL-17A in the plasma, lung and liver
      gradually increased with the extension of the experimental time in sepsis group,
      and were significantly higher than control group at 4 hours after injection of E
      coli (P < 0.01). In our study, we found the levels of IL-17A mRNA in pediatric
      sepsis group were significantly higher than control group, which is consistent
      with the neonatal rat septicemia model. In addition, through the functional (GO)
      enrichment analysis, we found the genes associated with IL-17A in pediatric
      sepsis are mainly enriched in the functions of immune response and cell membrane
      formation. CONCLUSION: IL-17A might be a potential therapeutic target for
      pediatric sepsis.

PMID- 30216520
TI  - A survey to assess use patterns and perceptions of efficacy of eczema action
      plans among pediatric dermatologists.
AB  - Eczema action plans (EAPs) are written, customizable documents that guide
      patients through the self-management of atopic dermatitis. Here, we distributed a
      survey regarding the use patterns and perceptions of eczema action plans to 1068
      members of the Society for Pediatric Dermatology and received 87 responses.
      Although a strong majority of respondents endorsed the ability of EAPs to improve
      adherence (79%) and improve prevention and/or management of flares (70%),
      reported rates of EAP editing or provision sharply decline from initial to follow
      up visits (61%-33%). The development of a standardized, low-literacy web-based
      tool could improve the efficacy of EAPs for patients and physicians by improving
      comprehensibility and retention.

PMID- 30216519
TI  - Verrucous hemangioma (also known as verrucous venous malformation): A vascular
      anomaly frequently misdiagnosed as a lymphatic malformation.
AB  - Verrucous hemangioma or verrucous venous malformation is a superficial venous
      malformation frequently misdiagnosed as a lymphatic malformation because of its
      classical hyperkeratotic appearance. Clinical characteristics of VVM were studied
      in patients with a histologically confirmed VVM, and validated in a prospective
      study of 18 patients. VVM was made of separated vascular elements with irregular
      shape, in a linear disposition, with variable thickness and keratosis. Its
      specific vascular pattern consisting of an erythematous patch with scattered
      small red to violet dots was easily identified using dermoscopy. In many cases,
      the typical clinical presentation of verrucous hemangioma is sufficient to
      establish the diagnosis and a biopsy may not be required.

PMID- 30216521
TI  - Keratocyst Capnocytophaga superinfection.
AB  - INTRODUCTION: Capnocytophaga spp are Gram-negative bacteria that cause severe
      infections in immunosuppressed patients. This situation is extremely rare in
      immunocompetent patients. CASE REPORT: This clinical report describes the unusual
      infection of an immunocompetent patient with Capnocytophaga spp. The imaging
      studies showed the existence of a cyst in the left jawbone. After treatment and a
      microbiological study of the content, it was found to be an outbreak of
      septicaemia. DISCUSSION: Capnocytophaga spp, commensal bacteria of the oral
      cavity, can lead to serious illness and that is why an empirical treatment is
      needed until a diagnostic confirmation can be obtained.

PMID- 30216522
TI  - Granulomatous dermatitis secondary to vemurafenib in a child with Langerhans cell
      histiocytosis.
AB  - We present a 3-year-old boy with Langerhans cell histiocytosis who developed
      granulomatous dermatitis while taking vemurafenib. Vemurafenib currently has Food
      and Drug Administration approval for the treatment of BRAF V600E+ metastatic
      melanoma in adults, but recent discoveries of BRAF V600E in more than half of
      tested Langerhans cell histiocytosis lesions have prompted clinical trials of
      vemurafenib therapy for children with refractory, multisystem Langerhans cell
      histiocytosis. This report contributes to the knowledge of its potential side
      effects when used in children.

PMID- 30216523
TI  - Suppression of BMX-ARHGAP fusion gene inhibits epithelial-mesenchymal transition
      in gastric cancer cells via RhoA-mediated blockade of JAK/STAT axis.
AB  - Gastric cancer (GC) is one of the main causes of cancer-related mortality
      worldwide. Epithelial-mesenchymal transition (EMT) is an important biological
      process involving the process by which malignant tumor cells obtain the ability
      of migration, invasion, resistance of apoptosis, and degradation in the
      extracellular matrix. The current study aimed at investigating whether bone
      marrow X kinase Rho GTPase activating protein 12 (BMX-ARHGAP) fusion gene affects
      GC. First, short hairpin RNA (shRNA) against BMX-ARHGAP or BMX-ARHGAP were
      introduced to treat SGC-7901 cells with the highest BMX-ARHGAP among the five GC
      cell lines (SGC-7901, MKN-45, NCI-N87, SNU-5, and AGS). Next, cell vitality, drug
      resistance, migration, and invasion of SGC-7901 cells, activities of Rho and
      JAK/STAT axis, as well as EMT and lymph node metastasis (LNM) were evaluated. The
      survival rate of the mice was then determined through the transfection of the
      specific pathogen-free NOD-SCID mice with treated SGC-7901 cells. The results
      showed that BMX-ARHGAP expression was associated with the infiltration degree of
      GC tumor and poor prognosis for patients with GC. BMX-ARHGAP silencing was found
      to play an inhibitory role in the Rho and JAK/STAT axis to reduce cell vitality,
      drug resistance, migration and invasion, reverse EMT process, as well as inhibit
      LNM. BMX-ARHGAP overexpression was observed to have induced effects on GC cells
      as opposed to those inhibited by BMX-ARHGAP silencing. The survival rate of mice
      was increased after transfection with silenced BMX-ARHGAP. These findings
      provided evidence that the suppression of BMX-ARHGAP resulted in the inhibition
      of RhoA to restraint the development of GC cells by blocking the JAK/STAT axis.

PMID- 30216525
TI  - Gestational diabetes incidence and delivery outcomes in Western China: A
      prospective cohort study.
AB  - BACKGROUND: Few studies have examined the age-standardized incidence of
      gestational diabetes mellitus (GDM) for comparison between populations.
      Information on delivery outcomes is also lacking for Chinese women with GDM.
      Therefore, the present study aimed to determine age-standardized GDM incidence
      and assess its association with maternal and neonatal outcomes. METHODS: A total
      of 1901 pregnant women were recruited in Chengdu, Sichuan Province. GDM was
      diagnosed between 24 and 28 weeks' gestation using oral glucose tolerance tests.
      Age-standardized incidence rates of GDM were calculated using the direct method.
      Delivery outcomes were extracted from medical records and compared between the
      GDM and non-GDM groups. RESULTS: The age-standardized GDM incidence was 18.3%
      (95% CI 15.6-21.1) and increased with maternal age and prepregnancy body mass
      index (BMI). Women with GDM experienced longer length of stay in hospital,
      shorter gestation at delivery, and a higher risk of cesarean delivery. Their
      newborns were more likely to be macrosomic or small for gestational age, and to
      require neonatal intensive care. CONCLUSIONS: The incidence of GDM was high in
      Western China, especially among older and overweight women. Moreover, women with
      GDM had higher rates of adverse delivery outcomes. The findings lend further
      support for the screening, prevention, and management of GDM in Chinese women.

PMID- 30216524
TI  - Angiosarcoma arising from congenital primary lymphedema.
AB  - We herein report the case of a 3-year-old girl with atypical congenital right
      upper limb lymphedema who developed an angiosarcoma. Only a few cases have been
      reported following congenital form of lymphedema and only 4 in such a young
      child. We also summarize all cases of angiosarcoma associated with congenital
      lymphedema reported in the literature.

PMID- 30216526
TI  - The feasibility and promise of mobile technology with community health worker
      reinforcement to reduce rural preterm birth.
AB  - OBJECTIVES: (1) Assess feasibility of a smartphone platform intervention combined
      with Community Health Worker (CHW) reinforcement in rural pregnant women; (2)
      Obtain data on the promise of the intervention on birth outcomes, patient
      activation, and medical care adherence; and (3) Explore financial implications of
      the intervention using return on investment (ROI). SAMPLE: A total of 98 rural
      pregnant women were enrolled and assigned to intervention or control groups in
      this two-group experimental design. INTERVENTION: The intervention group received
      usual prenatal care plus a smartphone preloaded with a tailored prenatal platform
      with automated texting, chat function, and hyperlinks and weekly contact from the
      CHW. The control group received usual prenatal care and printed educational
      materials. MEASUREMENTS: Demographics, health risk data, interaction with
      platform, medical records, hospital billing charges, Client Satisfaction
      Questionnaire-8, satisfaction comments, and the Patient Activation Measure.
      RESULTS: A total of 77 women completed the study. The intervention was well
      received, showed promise for improving birth outcomes, patient activation, and
      medical care adherence. Financial analysis showed a positive ROI under two
      scenarios. CONCLUSIONS: Despite several practical issues, the study appears
      feasible. The intervention shows promise for extending prenatal care and
      improving birth outcomes in rural communities. Further research is needed with a
      larger and more at-risk population to appreciate the impact of the intervention.

PMID- 30216527
TI  - Does clinical testing support the current guidance definition of prolonged
      contact for nickel allergy?
AB  - BACKGROUND: The European Chemical Agency (ECHA) definition of prolonged contact
      was introduced in 2014 and has not been evaluated clinically. OBJECTIVES: To
      assess whether nickel-sensitized individuals react on patch testing with high
      nickel-releasing metal discs for short and repetitive periods. MATERIALS AND
      METHODS: We patch tested 45 nickel-sensitized individuals double-blind with 2
      different types of high nickel-releasing discs for 10, 30 and 60 minutes on 3
      occasions over a period of 2 weeks, and for 1 longer period. Discs were tested
      for nickel release. RESULTS: Nickel release from both discs significantly
      exceeded the 0.5 MUg Ni/cm2 /week limit of the EU REACH nickel restriction.
      However, only 1 individual tested had a largely dose-dependent allergic reaction.
      CONCLUSIONS: The majority of nickel-allergic subjects did not react to nickel
      discs after 2 hours or after repetitive exposures of up to 30 minutes on 3
      occasions over a period of 2 weeks. The length of time needed to cause nickel
      allergic contact dermatitis in most nickel-allergic individuals is longer than
      the ECHA guidance definition. Longer test times are needed to define the time
      required to cause dermatitis in most nickel-allergic individuals. As a
      limitation, the test conditions did not adequately assess real-life factors such
      as friction, which is relevant for some uses of nickel.

PMID- 30216528
TI  - Calibration of methylene-referenced lipid-dissolved xenon frequency for absolute
      MR temperature measurements.
AB  - PURPOSE: Absolute MR temperature measurements are currently difficult because
      they require precalibration procedures specific for tissue types and conditions.
      Reference of the lipid-dissolved 129 Xe resonance frequency to temperature
      insensitive methylene protons (rLDX) has been proposed to remove the effect of
      macro- and microscopic susceptibility gradients to obtain absolute temperature
      information. The scope of this work is to evaluate the rLDX chemical shift (CS)
      dependence on lipid composition to estimate the precision of absolute temperature
      measurements in lipids. METHODS: Neat triglycerides, vegetable oils, and samples
      of freshly excised human and rodent adipose tissue (AT) are prepared under 129 Xe
      atmosphere and studied using high-resolution NMR. The rLDX CS is measured as a
      function of temperature. 1 H spectra are also acquired and the consistency of
      methylene-referenced water proton and rLDX CS values are compared in human AT.
      RESULTS: Although rLDX CS shows a dependence on lipid composition, in human and
      rodent AT samples the rLDX shows consistent CS values with a similar temperature
      dependence (-0.2058 +/- 0.0010) ppm/ degrees C * T ( degrees C) + (200.15 +/-
      0.03) ppm, enabling absolute temperature measurements with an accuracy of 0.3
      degrees C. Methylene-referenced water CS values present variations of up to 4
      degrees C, even under well-controlled conditions. CONCLUSIONS: The rLDX can be
      used to obtain accurate absolute temperature measurements in AT, opening new
      opportunities for hyperpolarized 129 Xe MR to measure tissue absolute
      temperature.

PMID- 30216529
TI  - Implementation process and quality of a primary health care system improvement
      initiative in a decentralized context: A retrospective appraisal using the
      quality implementation framework.
AB  - BACKGROUND: Effective implementation processes are essential in achieving desired
      outcomes of health initiatives. Whereas many approaches to implementation may
      seem straightforward, careful advanced planning, multiple stakeholder
      involvements, and addressing other contextual constraints needed for quality
      implementation are complex. Consequently, there have been recent calls for more
      theory-informed implementation science in health systems strengthening. This
      study applies the quality implementation framework (QIF) developed by Meyers,
      Durlak, and Wandersman to identify and explain observed implementation gaps in a
      primary health care system improvement intervention in Nigeria. METHODS: We
      conducted a retrospective process appraisal by analyzing contents of 39 policy
      document and 15 key informant interviews. Using the QIF, we assessed challenges
      in the implementation processes and quality of an improvement model across the
      tiers of Nigeria's decentralized health system. RESULTS: Significant process gaps
      were identified that may have affected subnational implementation quality. Key
      challenges observed include inadequate stakeholder engagements and poor fidelity
      to planned implementation processes. Although needs and fit assessments,
      organizational capacity building, and development of implementation plans at
      national level were relatively well carried out, these were not effective in
      ensuring quality and sustainability at the subnational level. CONCLUSIONS:
      Implementing initiatives between levels of governance is more complex than within
      a tier. Adequate preintervention planning, understanding, and engaging the
      various interests across the governance spectrum are key to improving quality.

PMID- 30216530
TI  - Toward 7T breast MRI clinical study: safety assessment using simulation of
      heterogeneous breast models in RF exposure.
AB  - PURPOSE: To facilitate assessment of RF power deposition and temperature rise
      within the breast, we present a method to seamlessly join heterogeneous breast
      models with standard whole-body models and demonstrate simulations at 7 T.
      METHODS: Finite-difference time-domain electromagnetic and bioheat simulations
      are performed to analyze the specific absorption rate (SAR) and temperature rise
      distributions in 36 Breast Imaging Reporting and Data System (BI-RADS)
      categorized breast models fused to 2 female whole-body models while transmitting
      from a 7T breast volume coil. The breast models are uncompressed in the prone
      position and feature heterogeneous tissue contents; fusion with human models uses
      affine transformation and the level-set method. RESULTS: The fusion method
      produces a continuous transient from the chest region to the posterior portion of
      breast models while preserving the original volume and shape of breast models.
      Simulation results of both Ella and Hanako models indicate that the maximum local
      SAR, partial body SAR, and local tissue temperature rise are positively
      correlated with both breast density and the highest BI-RADS density
      classification. Additionally, maximum local tissue temperature rise is positively
      correlated with maximum 10-g SAR values. CONCLUSION: Fibroglandular tissue
      content plays an important role in the distribution of SAR and temperature rise
      within breast tissue. The combined body-breast models preserve the integrity of
      breast models while concurrently exhibiting the loading of whole-body human
      models. The procedures presented in this simulation study facilitate safety
      assessments for breast MRI across the population at both clinical and ultrahigh
      field strengths.

PMID- 30216531
TI  - Women from racial or ethnic minority and low socioeconomic backgrounds receive
      more prenatal education: Results from the 2012 to 2014 Pregnancy Risk Assessment
      Monitoring System.
AB  - BACKGROUND: Racial or ethnic and socioeconomic disparities in adverse birth
      outcomes are well known, but few studies have examined disparities in the receipt
      of prenatal health education. The objectives of this study were to examine racial
      or ethnic and socioeconomic variations in receiving (1) comprehensive prenatal
      health education and (2) education about human immunodeficiency virus (HIV)
      testing, breastfeeding, alcohol, and smoking cessation from health care
      practitioners. METHODS: Data were drawn from the 2012 to 2014 Pregnancy Risk
      Assessment Monitoring System (PRAMS). Twenty-seven states were included with an
      analysis sample size of 68 025 participants. Receiving counseling on all listed
      health topics during prenatal care visits was denoted as comprehensive prenatal
      health education. Logistic regression was used to examine the association of
      racial or ethnic and socioeconomic variables with receiving comprehensive
      prenatal health education, and HIV testing, breastfeeding, alcohol, and smoking
      cessation advice separately. RESULTS: Multivariable results showed that racial or
      ethnic minorities and women with a high school degree or less; receiving Women,
      Infant, and Children (WIC) assistance; and on Medicaid during pregnancy have
      higher odds of receiving comprehensive prenatal health education (all P  <=0
      .001). Results were similar for receiving HIV testing, breastfeeding, alcohol,
      and smoking counseling. Low household income was associated with receiving
      counseling on HIV testing, alcohol, and smoking (all P <= 0.001). CONCLUSION:
      Despite reporting higher levels of prenatal health education on a variety of
      health-related topics, disadvantaged women continue to experience disparities in
      adverse birth outcomes suggesting that education is insufficient in promoting
      positive behaviors and birth outcomes.

PMID- 30216533
TI  - Pain and sleep disturbances in Rett syndrome and other neurodevelopmental
      disorders.

PMID- 30216532
TI  - Adverse effect of dexamethasone on development of the fetal rat ovary.
AB  - Dexamethasone (Dx) is often used in obstetric practice to promote fetal lung
      maturation and to prevent respiratory distress syndrome when the risk of preterm
      delivery persists. This therapy enables survival of the newborn, but also is
      associated with deleterious effects on the offspring, such as reproductive
      disorders. The aim of this study was to determine specifically whether prenatal
      exposure to Dx disturbs the physiological balance between proliferation and
      apoptosis of germinative cells (GC) in the ovary of 19- and 21-day-old fetuses
      and thus induces developmental programming of the female reproductive system.
      Pregnant Wistar rats (n = 10/group), separated into control (vehicle) and Dx
      treated (0.5 mg/kg body mass) groups, received injections on gestational days 16,
      17, and 18. Exposure to Dx lowered the volume of the fetal ovary by 30% (P <
      0.05) in 21-day-old fetuses, as well as the total number of GC in the ovary by
      21% (P < 0.05). When compared to the controls, in Dx-exposed fetuses, the total
      number of PCNA-positive GC was 27% lower at 19 days and 71% lower at 21 days old
      (P < 0.05), while total numbers of caspase-3-positive GC were 2.3-fold and 34%
      higher, respectively (P < 0.05). Our results demonstrate that prenatal exposure
      to Dx diminished proliferation but increased the rate of germinative cell
      apoptosis, with consequently reduced total germinative cell number and ovary
      volume. Impairment of fetal oogenesis and fewer GC in the fetal ovary compromise
      the oogonial stock and thus may constitute a risk of female fertility.

PMID- 30216535
TI  - Characterization of sulfuretin as a depigmenting agent.
AB  - Sulfuretin is a major flavonoid found in Rhus verniciflua and carries anti
      oxidative and anti-inflammatory properties, but its potential use in the control
      of skin pigmentation is unknown. The purpose of the present study was to
      elucidate sulfuretin as a new active compound inhibiting melanogenesis and the
      underlying mechanism. The effects of sulfuretin on melanin production, tyrosinase
      activity, cAMP level, and MITF expression were examined in murine melanoma B16
      cells challenged with forskolin or alpha-MSH. The inhibitory effect of sulfuretin
      on melanogenesis was further validated on neonatal human melanocytes. When tested
      in melanoma B16 cells treated with forskolin or alpha-MSH, sulfuretin inhibited
      the cellular melanogenesis. Sulfuretin also showed direct inhibitory effect on
      tyrosinase activity in vitro. In human primary melanocytes, the inhibitory effect
      of sulfuretin on melanin synthesis was also confirmed. Our current results
      support the depigmenting effect of sulfuretin and suggest a clinical strategy for
      using sulfuretin in the topical treatment of hyperpigmentation disorders.

PMID- 30216534
TI  - An mGlu4-Positive Allosteric Modulator Alleviates Parkinsonism in Primates.
AB  - BACKGROUND: Levodopa remains the gold-standard treatment for PD. However, it
      becomes less effective as the disease progresses and produces debilitating side
      effects, such as motor fluctuations and l-dopa-induced dyskinesia. Modulation of
      metabotropic glutamate receptor 4 represents a promising antiparkinsonian
      approach in combination with l-dopa, but it has not been demonstrated in
      primates. OBJECTIVE: We studied whether a novel positive allosteric modulator of
      the metabotropic glutamate receptor 4, PXT002331 (foliglurax), could reduce
      parkinsonism in primate models. METHODS: We assessed the therapeutic potential of
      PXT002331 in three models of MPTP-induced parkinsonism in macaques. These models
      represent three different stages of disease evolution: early stage and advanced
      stage with and without l-dopa-induced dyskinesia. RESULTS: As an adjunct to l
      dopa, PXT002331 induced a robust and dose-dependent reversal of parkinsonian
      motor symptoms in macaques, including bradykinesia, tremor, posture, and
      mobility. Moreover, PXT002331 strongly decreased dyskinesia severity, thus having
      therapeutic efficacy on both parkinsonian motor impairment and l-dopa-induced
      dyskinesia. PXT002331 brain penetration was also assessed using PET imaging in
      macaques, and pharmacodynamic analyses support target engagement in the
      therapeutic effects of PXT002331. CONCLUSIONS: This work provides a demonstration
      that a positive allosteric modulator of metabotropic glutamate receptor 4 can
      alleviate the motor symptoms of PD and the motor complications induced by l-dopa
      in primates. PXT002331 is the first compound of its class to enter phase IIa
      clinical trials. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 30216536
TI  - Single-operator cholangioscopy for the treatment of concomitant gallbladder
      stones and secondary common bile duct stones.
AB  - BACKGROUND AND AIM: This study aims to assess the clinical validity and safety of
      single-operator cholangioscopy system (SOCS) for the treatment of concomitant
      gallbladder stones and secondary common bile duct (CBD) stones. METHODS: This
      retrospective study included 10 consecutive patients who had small-sized stones
      (< 1 cm) in both the gallbladder and CBD; the patients underwent SOCS treatment
      from June 2016 to December 2016. The clinical validity of this minimally invasive
      surgery was determined by the operation success rate, stone removal rate,
      postoperative hospital stay, hospitalization cost, and contrast images before and
      after the operation. The clinical safety was evaluated by perioperative
      complications and outcomes, gallbladder stone recurrence, and gallbladder
      contractility function. RESULTS: Both the technique success rate and the stone
      removal rate when using SOCS was 100%. There were no serious complications that
      occurred during the operation; three patients developed acute cholecystitis, and
      four patients underwent hyperamylasemia after the surgery. The average
      postoperative hospital stay was 5.8 +/- 1.32 days, and the average
      hospitalization cost was 7466 +/- 566.1 dollars. In the follow-up period, which
      ranged from 3 to 8 months, there was no stone residuals or recurrences in the
      gallbladder and CBD, and no patient showed a recurrence of biliary colic. In
      addition, the gallbladder contractility function was proven to be normal within 3
      to 6 months after the operation. CONCLUSIONS: SOCS could successfully manage
      concomitant gallbladder stones and secondary CBD stones and precisely protect
      normal biliary function.

PMID- 30216537
TI  - Assessing and managing Parkinson's disease from home: A 21st century vision
      closer to reality.

PMID- 30216538
TI  - Agomelatine pretreatment prevents development of hyperglycemia and
      hypoinsulinemia in streptozotocin-induced diabetes in mice.
AB  - The main objective of this study was to investigate potential effectiveness of
      agomelatine pretreatment in the prevention of diabetes itself and encephalopathy,
      with a focus on brain tissue oxidative stress and inflammatory processes in
      streptozotocin (STZ)-induced diabetic mice. Interleukine-1beta (IL-1beta) and
      TACR1 (NK1), which is a tachykinine receptor, were used for the investigation of
      inflammation in the brain regions including raphe nucleus, periaqueductal gyrus
      (PAG), amygdala, and nucleus accumbens. The effects of agomelatine on total
      antioxidant capacity were also evaluated. In the in vitro part of the study, the
      effects of agomelatine on cell viability were investigated in dorsal root
      ganglion (DRG) neurons. Fasting blood glucose levels were measured 72 h after STZ
      injection to determine the diabetic condition. Agomelatine pretreatment prevented
      both hyperglycemia and hypoinsulinemia in STZ-treated mice. When STZ was injected
      to induce diabetes in mice, neither hyperglycemia nor hypoinsulinemia was
      developed in agomelatine pretreated mice and 6 weeks after development of
      diabetes, agomelatine treatment significantly decreased levels of IL-1beta mRNA
      in raphe nucleus and nucleus accumbens. TACR1 mRNA levels were lower in raphe
      nucleus, PAG, and amygdala of agomelatine-treated diabetic mice. The increase in
      total antioxidant capacity after agomelatine administration may responsible for
      its beneficial effect in the prevention of diabetes. We showed that agomelatine
      reversed high glucose-induced cell viability decreases in DRG neurons. Both the
      antihyperglycemic and antioxidant effects of agomelatine might have contributed
      to the DRG neuron viability improvement. In conclusion, agomelatine seems to both
      prevent development of diabetes and reverse the encephalopathic changes caused by
      diabetes.

PMID- 30216539
TI  - Tor1a gene in GABApre interneurons: The new player in the "impaired inhibition"
      game of dystonia?

PMID- 30216540
TI  - TIMP Loss Activates Metalloproteinase-TNFalpha-DKK1 Axis To Compromise Wnt
      Signaling and Bone Mass.
AB  - Deregulated proteolysis invariably underlies most human diseases including bone
      pathologies. Metalloproteinases constitute the largest of the five protease
      families, and the metzincin metalloproteinases are inhibited by the four tissue
      inhibitors of metalloproteinase called TIMPs. We hypothesized that Timp genes are
      essential for skeletal homeostasis. We bred individual Timp knockout mice to
      generate unique mouse models, the quadruple Timp null strain (QT) as well as mice
      harboring only a single Timp3 allele (QT3+/- ). QT mice are grossly smaller and
      exhibit a dramatic reduction of trabeculae in long bones by MUCT imaging with a
      corresponding increase in metalloproteinase activity. At the cellular level, Timp
      deficiency compromised differentiation markers, matrix deposition and
      mineralization in neonatal osteoblasts from calvariae, as well as the
      fibroblastic colony-forming unit (CFU-F) capacity of bone marrow-derived stromal
      cells. In contrast, we observed that osteoclasts were overactive in the Timp null
      state, consistent with the noted excessive bone resorption of QT bones.
      Immunohistochemistry (IHC) and immunofluorescence (IF) analyses of bone sections
      revealed higher Cathepsin K and RANKL signals upon Timp loss. Seeking the
      molecular mechanism, we identified abnormal TNFalpha bioactivity to be a central
      event in Timp-deficient mice. Specifically, TNFalpha triggered induction of the
      Wnt signaling inhibitor Dkk1 in the osteoblasts at the mRNA and protein levels,
      with a simultaneous increase in RANKL. Neutralizing TNFalpha antibody was capable
      of rescuing the induction of Dkk1 as well as RANKL. Therefore, the generation of
      novel Timp-deficient systems allowed us to uncover the essential and collective
      function of TIMP proteins in mammalian long-bone homeostasis. Moreover, our study
      discovers a functional TIMP/metalloproteinase-TNFalpha-Dkk1/RANKL nexus for
      optimal control of the bone microenvironment, which dictates coexistence of the
      osteoblast and osteoclast lineages. (c) 2018 American Society for Bone and
      Mineral Research.

PMID- 30216542
TI  - A novel Parkinson's disease risk variant, p. W378R, in the Gaucher's disease GBA
      gene.

PMID- 30216541
TI  - Detecting Mild Cognitive Deficits in Parkinson's Disease: Comparison of
      Neuropsychological Tests.
AB  - BACKGROUND: Numerous neuropsychological tests and test versions are used in
      Parkinson's disease research, but their relative capacity to detect mild
      cognitive deficits and their comparability across studies are unknown. The
      objective of this study was to identify neuropsychological tests that
      consistently detect cognitive decline in PD across studies. METHODS: Data from 30
      normed neuropsychological tests across 20 international studies in up to 2908
      nondemented PD patients were analyzed. A subset of 17 tests was administered to
      up to 1247 healthy controls. A 2-step meta-analytic approach using standardized
      scores compared performance in PD with normative data. RESULTS: Pooled estimates
      of the differences between PD and site-specific healthy controls identified
      significant cognitive deficits in PD patients on 14 test scores across 5 commonly
      assessed cognitive domains (attention or working memory, executive, language,
      memory, and visuospatial abilities), but healthy control performance was
      statistically above average on 7 of these tests. Analyses based on published
      norms only, as opposed to direct assessment of healthy controls, showed high
      between-study variability that could not be accounted for and led to inconclusive
      results. CONCLUSIONS: Normed neuropsychological tests across multiple cognitive
      domains consistently detect cognitive deficits in PD when compared with site
      specific healthy control performance, but relative PD performance was
      significantly affected by the inclusion and type of healthy controls versus the
      use of published norms only. Additional research is needed to identify a
      cognitive battery that can be administered in multisite international studies and
      that is sensitive to cognitive decline, responsive to therapeutic interventions,
      and superior to individual cognitive tests. (c) 2018 International Parkinson and
      Movement Disorder Society.

PMID- 30216543
TI  - Functional monoamine oxidase B gene intron 13 polymorphism predicts putaminal
      dopamine turnover in de novo Parkinson's disease.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of common
      functional polymorphisms in genes involved in dopamine metabolism on striatal
      dopamine turnover in de novo Parkinson's disease (PD). METHODS: This was an
      observer-blinded cohort study investigating effects of common functional
      polymorphisms in dopa decarboxylase (DDC, rs921451), monoamine oxidase B (MAOB;
      rs1799836), catechol-O-methyltransferase (COMT, rs4680), and dopamine
      transporter/solute carrier family 6 member 3 (DAT/SLC6A3, variable number tandem
      repeats) genes on 18 F-fluorodopa uptake and an effective distribution volume
      ratio (inverse of dopamine turnover) measured by 18 F-fluorodopa PET in 28
      untreated PD patients. RESULTS: Patients carrying the MAOBCC/(C)/CT genotype
      (low/intermediate enzyme activity) had a lower dopamine turnover in the putamen
      (higher mean effective distribution volume ratio) when compared with patients
      with MAOBTT/(T) genotype (high enzyme activity). Striatal PET measures were not
      different between variants in the remaining genes. CONCLUSIONS: The MAOB
      (rs1799836) polymorphism predicts putaminal dopamine turnover in early PD with
      the MAOBTT allele linked to high enzyme activity leading to higher intrinsic
      dopamine turnover, which has been demonstrated to constitute a risk factor for
      motor complications. (c) 2018 The Authors. Movement Disorders published by Wiley
      Periodicals, Inc. on behalf of International Parkinson and Movement Disorder
      Society.

PMID- 30216545
TI  - A new method of choice for organoleptic scoring: The negative-pressure technique.
AB  - AIM: To examine an organoleptic scoring method (OLS) whereby the sample is
      collected by negative pressure in a syringe and is subsequently smelled and rated
      away from the patient. MATERIALS AND METHODS: Data of 476 patients visiting a
      specialized halitosis clinic in Leuven (Belgium) were reviewed retrospectively.
      Organoleptic (with the classic and with the negative-pressure method) and
      instrumental (with the Halimeter(r) and OralChromaTM ) ratings of breath odour
      were retrieved from patient files together with the final diagnosis. The
      correlations between the different methods were examined (Spearman correlation
      coefficient) as well as the positive (PPV) and negative predictive value (NPV),
      sensitivity and specificity of all methods. RESULTS: Both methods of OLS
      correlated similarly with the instrumental measurements (Halimeter(r) and
      OralChromaTM ). Analysis of PPV, NPV, sensitivity and specificity of both methods
      of examination showed that the negative-pressure method performed best.
      CONCLUSION: The negative-pressure method is a valid method for organoleptic
      scoring of the breath odour and performs as good as the classic organoleptic
      method.

PMID- 30216544
TI  - Mitochondrial Function Is Compromised in Cortical Bone Osteocytes of Long-Lived
      Growth Hormone Receptor Null Mice.
AB  - Despite increased longevity and resistance to multiple stressors, growth hormone
      receptor null (GHRKO) mice exhibit severe skeletal impairment. The role of GHR in
      maintaining osteocyte mitochondrial function is unknown. We found that GHR
      ablation was detrimental to osteocyte mitochondrial function. In vivo multiphoton
      microscopy revealed significant reductions of >10% in mitochondrial membrane
      potential (MMP) in GHRKO osteocytes and reduced mitochondrial volumetric density.
      Reductions in MMP were accompanied by reductions in glucose transporter-1 levels,
      steady state ATP, NADH redox index, oxygen consumption rate, and mitochondrial
      reserve capacity in GHRKO osteocytes. Glycolytic capacity did not differ between
      control and GHRKO males' osteocytes. However, osteocytes from aged female GHRKO
      mice exhibited reductions in glycolytic parameters, indicating impairments in
      glucose metabolism, which may be sex dependent. GHRKO osteocytes exhibited
      increased levels of cytoplasmic reactive oxygen species (ROS) (both basal and in
      response to high glucose), insulin-like growth factor-1 (IGF-1), and insulin.
      Mitochondrial ROS levels were increased and correlated with reduced glutathione
      in GHRKO osteocytes. Overall, the compromised osteocyte mitochondrial function
      and responses to metabolic insults strongly correlated with skeletal impairments,
      suggesting that despite increased life span of the GHRKO mice, skeletal health
      span is decreased. (c) 2018 American Society for Bone and Mineral Research.

PMID- 30216547
TI  - Assessment of the mutagenic potential of para-chloroaniline and aniline in the
      liver, spleen, and bone marrow of Big Blue(r) rats with micronuclei analysis in
      peripheral blood.
AB  - Splenic tumors have been reported in rat cancer bioassays with para-chloroaniline
      (PCA) and aniline. Development of these tumors is hypothesized to be due to
      hematotoxicity via the formation of methemoglobin (MetHb) and not direct DNA
      reactivity. To evaluate the mode of action (MOA) for tumor formation a transgenic
      rodent (TGR) in vivo gene mutation assay in Big Blue(r) TgF344 rats was performed
      with parallel micronuclei analysis in peripheral blood. Male rats were gavaged
      daily for 28 d to 0.5, 15, and 60 mg/kg PCA and 100 mg/kg aniline, the base
      molecular structure of PCA. On test day 10, the 60 mg/kg PCA dose was reduced to
      30 mg/kg due to toxicity. On test day 4 and 29 peripheral blood micronucleus
      analysis was performed and on test day 29 clinical chemistry, hematology, and
      MetHb measurements were taken. At study termination, on test day 31, spleen, bone
      marrow, and liver (control tissue) were analyzed for cII transgene mutant
      frequency (MF). Repeat gavage exposure to PCA and aniline for 28 d did not
      produce an increase in cII transgene MF in analyzed tissues. An increase in
      micronuclei was seen at both time points at >=15 mg/kg PCA and 100 mg/kg aniline.
      At the same dose levels, significant reductions in red blood cells, increases in
      absolute reticulocytes (ABRET), and increased levels of MetHb were observed.
      Together these results support that generation of micronuclei and tumorigenicity
      following exposure to PCA and aniline is due to compensatory mechanisms (e.g.
      increased cellular turnover) and not direct DNA reactivity. Environ. Mol.
      Mutagen. 59:785-797, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30216546
TI  - Newborn foal with atypical myopathy.
AB  - The case of atypical myopathy (AM) in newborn Haflinger foal with clinical signs
      of depression and weakness appearing 6 hours after birth resulting in recumbency
      12 hours after birth is described. The foal's dam was diagnosed with AM in the
      6th month of gestation based on clinical signs of a myopathy, elevated serum
      activity of creatine kinase, metabolomic analysis and the presence of
      methylenecyclopropyl acetyl carnitine (MCPA-carnitine) in the blood. At the time
      of delivery, the mare was grazing on a pasture near sycamore trees but was free
      of clinical signs of AM. Metabolomic analysis of the foal's blood revealed
      increased concentrations of acylcarnitines and MCPA-carnitine consistent with
      metabolic profiles of blood from AM affected horses. Two theories could explain
      this observation (a) hypoglycin A or its metabolites accumulated in the mare's
      placenta with consequent transfer to fetus or (b) these compounds were secreted
      into mare's milk.

PMID- 30216548
TI  - Illuminating the optimal anastomosis site with optical coherence tomography in
      coronary artery bypass surgery.

PMID- 30216549
TI  - Effect of prespecified therapy escalation on plasma NT-proBNP concentrations in
      dogs with stable congestive heart failure due to myxomatous mitral valve disease.
AB  - BACKGROUND: Treatment targeted to achieve reduction in N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) improves outcomes in human congestive heart
      failure (CHF) patients. HYPOTHESIS: A pre-specified therapeutic algorithm that
      increased diuretic or pimobendan usage will reduce plasma NT-proBNP
      concentrations in dogs with CHF secondary to myxomatous mitral valve disease
      (MMVD). ANIMALS: Twenty-six dogs with clinically stable CHF secondary to MMVD.
      METHODS: Prospective, controlled before-and-after study. Dogs were examined up to
      3 times over 21 days. Treatment was prescribed based on NT-proBNP as follows:
      <1500 pmol/L at baseline, no treatment adjustment at any point during the study
      (group 1); >=1500 pmol/L and creatinine <=3.0 mg/dL at baseline or SC visits,
      treatment escalated according to the algorithm (group 2); >=1500 pmol/L at
      baseline, no treatment adjustment (group 3). RESULTS: N-terminal pro-B-type
      natriuretic peptide decreased significantly in group 2 (mean change = -1736
      pmol/L (95% CI, -804 to -2668), P < .001) but not in groups 1 or 3 (623 pmol/L [
      631 to 1877 pmol/L], P = .14 and 685 pmol/L [-304 to 1068 pmol/L], P = .46,
      respectively). Serum BUN and creatinine did not change significantly between
      visit 0 and visit 2 in group 1 (median = 23 mg/dL [range 13-32] versus 19 mg/dL
      [12-38], P = .72 and 1.15 mg/dL [0.70-1.40] versus 0.95 mg/dL [0.70-1.10], P =
      .10, respectively) or group 2 (28 mg/dL [18-87] versus 43.5 mg/dL [21-160], P =
      .092 and 1.10 mg/dL [0.90-2.50] versus 1.55 mg/dL [0.90-3.30], P = .062,
      respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Use of this treatment
      escalation algorithm allows effective targeting of treatment for CHF in dogs
      against an objective criterion.

PMID- 30216550
TI  - Variability of serum concentrations of cystatin C and urinary retinol-binding
      protein, neutrophil gelatinase-associated lipocalin, immunoglobulin G, and C
      reactive protein in dogs.
AB  - BACKGROUND: Markers of kidney dysfunction and damage have potential to detect
      chronic kidney disease (CKD) in early stages. However, data on long-term
      variation of these markers in healthy dogs is lacking and is crucial for the
      interpretation of results. HYPOTHESIS/OBJECTIVES: To determine temporal
      variations of serum cystatin C (sCysC) and urinary retinol-binding protein
      (uRBP), neutrophil gelatinase-associated lipocalin (uNGAL), immunoglobulin G
      (uIgG), and C-reactive protein (uCRP) in healthy dogs. ANIMALS: Eight clinically
      healthy adult Beagles were evaluated. METHODS: Longitudinal observational study.
      Serum cystatin C was determined by particle-enhanced nephelometric immunoassay.
      Urinary retinol-binding protein, uNGAL, uIgG and uCRP were determined by ELISA
      and concentrations were indexed to urinary creatinine. Within- and between-dog
      variance components (VC) and within-dog coefficients of variation (CV) were
      determined from blood and urine collected at eight time points over 1.5 years.
      RESULTS: Urinary C-reactive protein (uCRP) concentrations were consistently below
      the detection limit (5.28 ng/mL). Mean +/- within-dog standard deviation for
      sCysC, uRBP/c, uNGAL/c and uIgG/c was 0.15 +/- 0.01 mg/L, 0.09 +/- 0.03 mg/g,
      2.32 +/- 2.03 MUg/g and 12.47 +/- 10.98 mg/g, respectively. Within-dog CV for
      sCysC, uRBP/c, uNGAL/c and uIgG/c was 8.1%, 33.7%, 87.2% and 88.1%, respectively.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Serum cystatin C, uRBP/c, uNGAL/c and uIgG/c
      exhibit a wide range of long-term within-dog variability. Researchers and
      veterinarians might need to take this into account when interpreting their
      results. To assess their diagnostic and predictive ability, future studies need
      to establish reference ranges for healthy dogs and dogs with CKD.

PMID- 30216551
TI  - The effect of completeness of revascularization during CABG with single versus
      multiple arterial grafts.
AB  - INTRODUCTION: Incomplete coronary revascularization is associated with suboptimal
      outcomes. We investigated the long-term effects of Incomplete, Complete, and
      Supra-complete revascularization and whether these effects differed in the
      setting of single-arterial and multi-arterial coronary artery bypass graft
      (CABG). METHODS: We analyzed 15-year mortality in 7157 CABG patients (64.1 +/-
      10.5 years; 30% women). All patients received a left internal thoracic artery to
      left anterior descending coronary artery graft with additional venous grafts only
      (single-arterial) or with at least one additional arterial graft (multi-arterial)
      and were grouped based on a completeness of revascularization index (CRI = number
      of grafts minus the number of diseased principal coronary arteries): Incomplete
      (CRI <= -1 [N = 320;4.5%]); Complete (CRI = 0 [N = 2882;40.3%]; reference group);
      and two Supra-complete categories (CRI = +1[N = 3050; 42.6%]; CRI >= + 2 [N =
      905; 12.6%]). Risk-adjusted mortality hazard ratios (AHR) were calculated using
      comprehensive propensity score adjustment by Cox regression. RESULTS: Incomplete
      revascularization was rare (4.5%) but associated with increased mortality in all
      patients (AHR [95% confidence interval] = 1.53 [1.29-1.80]), those undergoing
      single-arterial CABG (AHR = 1.27 [1.04-1.54]) and multi-arterial CABG (AHR = 2.18
      [1.60-2.99]), as well as in patients with 3-Vessel (AHR = 1.37 [1.16-1.62]) and,
      to a lesser degree, with 2-Vessel (AHR = 1.67 [0.53-5.23]) coronary disease.
      Supra-complete revascularization was generally associated with incrementally
      decreased mortality in all patients (AHR [CRI = +1] = 0.94 [0.87-1.03]); AHR [CRI
      >= +2] = 0.74 [0.64-0.85]), and was driven by a significantly decreased mortality
      risk in single-arterial CABG (AHR [CRI = +1] = 0.90 [0.81-0.99]; AHR [CRI >= +2]
      = 0.64 [0.53-0.78]); and 3-Vessel disease patients (AHR [CRI = +1] = 0.94 [0.86
      1.04]; and AHR [CRI >= +2] = 0.75 [0.63-0.88]) with no impact in multi-arterial
      CABG (AHR [CRI = +1] = 1.07 [0.91-1.26]; AHR [CRI >= +2] = 0.93 [0.73-1.17]).
      CONCLUSIONS: Incomplete revascularization is associated with decreased late
      survival, irrespective of grafting strategy. Alternatively, supra-complete
      revascularization is associated with improved survival in patients with 3-Vessel
      CAD, and in single-arterial but not multi-arterial CABG.

PMID- 30216553
TI  - Striatum: Through the looking glass.

PMID- 30216552
TI  - Atrioventricular accessory pathways in 89 dogs: Clinical features and outcome
      after radiofrequency catheter ablation.
AB  - BACKGROUND: Atrioventricular accessory pathways (APs) in dogs have been reported
      rarely. Data regarding clinical presentation and long-term outcome after
      radiofrequency catheter ablation (RFCA) are limited. HYPOTHESIS/OBJECTIVES: To
      study clinical features, electrophysiologic characteristics, and outcome of RFCA
      in dogs with APs. ANIMALS: Eighty-nine dogs presented consecutively for RFCA of
      APs. METHODS: Case series. RESULTS: Labrador retrievers (47.2% of dogs) and male
      dogs (67.4% of dogs) were most commonly affected. Labrador retrievers were more
      likely to be male than non-Labrador breeds (P = .043). Clinical signs were
      nonspecific and most commonly included lethargy and gastrointestinal signs.
      Concealed APs were more prevalent in Labrador retrievers than other breeds (P =
      .001). Right-sided APs (91.7%) predominated over left-sided (8.3%). Tachycardia
      induced cardiomyopathy (TICM) occurred in 46.1% of dogs, with complete resolution
      or substantial improvement noted on one-month postablation echocardiograms.
      Radiofrequency catheter ablation successfully eliminated AP conduction long term
      in 98.8% of dogs in which it was performed. Complications occurred in 5/89 dogs.
      Recurrence in 3 dogs was eliminated long term with a second procedure. CLINICAL
      IMPORTANCE/CONCLUSIONS: Accessory pathways are challenging to recognize in dogs
      because of nonspecific clinical signs, frequency of concealed APs that show no
      evidence of their presence during sinus rhythm, and intermittent occurrence of
      tachyarrhythmias resulting from APs. Tachycardia-induced cardiomyopathy commonly
      occurs with AP-mediated tachycardias and should be considered in any dog
      presenting with a dilated cardiomyopathic phenotype because of its good long-term
      prognosis with rhythm control. Radiofrequency catheter ablation is a highly
      effective method for eliminating AP conduction and providing long-term
      resolution.

PMID- 30216554
TI  - Acute Tissue Mineral Deposition in Response to a Phosphate Pulse in Experimental
      CKD.
AB  - Pathogenic accumulation of calcium (Ca) and phosphate (PO4 ) in vasculature is a
      sentinel of advancing cardiovascular disease in chronic kidney disease (CKD).
      This study sought to characterize acute distribution patterns of radiolabeled 33
      PO4 and 45 Ca in cardiovascular tissues of rats with CKD (0.25% dietary adenine).
      The disposition of 33 PO4 and 45 Ca was assessed in blood and 36 tissues after a
      10-minute intravenous infusion of one of the following: (i) PO4  pulse + tracer
      33 PO4 ; (ii) PO4  pulse + tracer 45 Ca; or (iii) saline + tracer 45 Ca in CKD
      and non-CKD animals. After the infusion, 33 PO4 in blood was elevated (2.3* at 10
      minutes, 3.5* at 30 minutes, p < 0.05) in CKD compared with non-CKD. In contrast,
      there was no difference in clearance of 45 Ca from the blood. Compared with
      controls, CKD rats had a markedly increased 33 PO4 incorporation in several
      tissues (skeletal muscle, 7.8*; heart, 5.5*), but accrual was most pronounced in
      the vasculature (24.8*). There was a significant, but smaller, increase in 45 Ca
      accrual in the vasculature of CKD rats (1.25*), particularly in the calcified
      rat, in response to the acute phosphate load. Based on the pattern of tissue
      uptake of 33 PO4 and 45 Ca, this study revealed that an increase in circulating
      PO4 is an important stimulus for the accumulation of these minerals in vascular
      tissue in CKD. This response is further enhanced when vascular calcification is
      also present. The finding of enhanced vascular mineral deposition in response to
      an acute PO4  pulse provides evidence of significant tissue-specific
      susceptibility to calcification. (c) 2018 American Society for Bone and Mineral
      Research.

PMID- 30216555
TI  - Minimally invasive, robot-assisted procedure for kidney transplantation among
      morbidly obese: Positive outcomes at 5 years post-transplant.
AB  - The pre-transplant weight loss required of end-stage renal disease patients is
      often unachievable. Though robot-assisted procedures among extremely obese have
      shown minimal complication, long-term outcomes are understudied. Previously, we
      reported no difference in 6-month patient and graft survival among 28 robot
      assisted transplant cases (2009-2013) and 28 open controls (2004-2010). Groups
      were frequency-matched on age, sex, race, donor compatibility, disease, and
      dialysis history. Cases had greater median pre-transplant body mass index (BMI;
      42.3 (31.1-64.3) vs 36.8 (30.0-51.1)). Here, we compared patient and graft
      survival through 5 years post-transplant. Infection, wound complications, and
      significant re-hospitalizations were collected. One-, three-, and five-year graft
      survival were 100%, 100%, and 89.3% among cases, and 96.4%, 85.7%, and 78.6%
      among controls. Rejection within 1 year was greater among cases (11 vs 8). Five
      year rates were similar (P = 0.54). Post-transplant BMI remained comparable. No
      cases and eight controls experienced surgical site infection (SSI). Two cases and
      one control experienced hernias. Post-transplant diabetes was documented among
      five cases and six controls. Three deaths occurred among cases, two among
      controls. This is the most extensive known follow-up of such obese recipients of
      robot-assisted transplant. Our procedure is a promising pathway to transplant and
      decreased mortality for those deemed too high risk for conventional surgery.

PMID- 30216556
TI  - Autopsy case of V180I genetic Creutzfeldt-Jakob disease presenting with early
      disease pathology.
AB  - The patient was a Japanese woman who experienced a decrease in activity and gait
      disturbance as the initial symptoms at the age of 86, followed by disorientation
      and memory dysfunction. Magnetic resonance imaging showed extensive cortical
      regions with hyperintensity in diffusion-weighted images, and these regions
      showed swelling in T2-weighted and fluid-attenuated inversion recovery (FLAIR)
      images. The medial occipital cortex and striatum showed no apparent
      hyperintensity on diffusion-weighted imaging (DWI). Mild myoclonus was detected,
      and the patient died 10 months after the onset of symptoms; she did not enter the
      akinetic mutism state. The patient's brain weighed 1050 g, and neuropathological
      examination showed extensive characteristic various-sized and non-confluent
      (VaSNoC) vacuoles in the cerebral cortex. These vacuoles were observable
      macroscopically by loupe on images of hematoxylin and eosin-stained tissue.
      Gliosis, hypertrophic astrocytosis, and neuron loss were generally mild in
      character. Prion protein (PrP) immunostaining showed very mild diffuse-synaptic
      type PrP deposition in the cerebral gray matter. These clinicopathological
      findings led us to several conclusions relative to the early disease pathology of
      V180I genetic Creutzfeldt-Jakob disease: (i) spongiform change was not found in
      the medial occipital cortex, which corresponds to the results of DWI; (ii) VaSNoC
      type spongiform changes, extensively recognized in the cerebral cortex,
      corresponded to the DWI findings showing continued hyperintensity with higher
      brightness, and T2-weighted and FLAIR images findings showing a swelling; and
      (iii) spongiform changes first appear in the deeper layer and subsequently in the
      superficial layer in the cerebral cortex.

PMID- 30216558
TI  - Survival associated with cerebrospinal fluid analysis in downer adult dairy cows:
      A retrospective study (2006-2014).
AB  - BACKGROUND: Threshold values for total nucleated cell count (TNCC) and protein
      concentration in cerebrospinal fluid (CSF) of downer dairy cows suggestive of a
      spinal cord lesion were recently published. OBJECTIVES: Determine short- and long
      term survival of downer cows that underwent CSF analysis using the reported
      threshold values. Evaluate the prognostic value of these threshold values to
      predict short- and long-term survival. ANIMALS: Two hundred and fourteen downer
      adult dairy cows that underwent CSF analysis during hospitalization at the Centre
      Hospitalier Universitaire Veterinaire (CHUV) of the Universite de Montreal.
      METHODS: Retrospective study. Medical records of downer adult dairy cows
      presented to the hospital between January 2006 and October 2014 for which CSF
      analysis results were available were studied. Short-term (discharge from
      hospital) and long-term (completion of lactation) survival were determined and
      compared in accordance with CSF TNCC and protein concentration, using a Chi
      square test. RESULTS: Cows with CSF TNCC and/or protein concentration above the
      threshold values had a significantly lower short-term survival rate (P = .02).
      The odds of nonsurvival of cows with one or both CSF values above the threshold
      values was 2.16 times higher than the odds for cows with values under the
      threshold values. CSF TNCC >4.5 cells/MUL had sensitivity and specificity of
      17.3% (95% CI: 10.7%-25.7%) and 92.3% (95% CI: 85.4%-96.6%), respectively, for
      predicting short-term nonsurvival. CSF protein concentration >0.39 g/L had
      sensitivity and specificity of 20.9% (95% CI: 13.7%-29.7%) and 91.4% (95% CI:
      84.2%-96.0%), respectively. CONCLUSIONS: CSF analysis above threshold values used
      in this study is associated with increased odds of short-term nonsurvival.

PMID- 30216557
TI  - Seizure occurrence in dogs under primary veterinary care in the UK: prevalence
      and risk factors.
AB  - BACKGROUND: Primary-care veterinary clinical records can offer data to determine
      generalizable epidemiological data on seizures occurrence in the dog population.
      OBJECTIVES: To identify and examine epidemiologic characteristics of seizure
      occurrence in dogs under primary veterinary care in the UK participating in the
      VetCompassTM Programme. ANIMALS: 455,553 dogs in VetCompassTM'. METHODS: A cross
      sectional analysis estimated the 1-year period prevalence and risk factors for
      dogs with seizures during 2013. RESULTS: The overall 1-year period prevalence for
      dogs having at least one seizure during 2013 was 0.82% (95% CI 0.79-0.84).
      Multivariable modelling identified breeds with elevated odd ratios [OR] compared
      with the Labrador Retriever (e.g. Pug OR: 3.41 95% CI 2.71-4.28, P < 0.001).
      Males had higher risk for seizures (Male/Entire OR: 1.47 95% CI 1.30-1.66;
      Male/Neutered OR: 1.34 95% CI 1.19-1.51) compared to entire females. Age (3.00 -
      <= 6.00 OR: 2.13 95% CI 1.90-2.39, P < 0.001, compared to animals aged 0.50-<=
      3.00 years), and bodyweight (>= 40.00kg, OR: 1.24 95% CI 1.08-1.41, P = 0.002,
      compared to animals weighing < 10.0 kg) were identified as risk factors for
      seizures. CONCLUSION AND CLINICAL IMPORTANCE: Seizures are a relatively common
      clinical finding in dogs. The results for breed, age, sex and bodyweight as risk
      factors can assist veterinarians in refining differential diagnosis lists for
      dogs reported with behaviors that may have been seizures. In addition, the
      prevalence values reported here can support pharmacovigilance with baseline data
      from the overall population.

PMID- 30216559
TI  - Utility of C-reactive protein and serum amyloid A in the diagnosis of equine
      protozoal myeloencephalitis.
AB  - BACKGROUND: Accurate antemortem EPM diagnosis requires evidence of intrathecal
      antibody production. Some advocate the use of acute phase proteins in addition to
      serology, which alone results in substantial false positives.
      HYPOTHESIS/OBJECTIVES: The purpose of this study was to determine if serum C
      reactive protein (CRP) or serum amyloid A (SAA) concentrations were elevated in
      cases of equine protozoal myeloencephalitis (EPM) compared to other neurological
      diseases. ANIMALS: 25 clinical cases of equine neurological disease: EPM (10),
      cervical vertebral stenotic myelopathy (CVSM) (10), neuroborreliosis (2), equine
      motor neuron disease (1), degenerative myelopathy (1), and leukoencephalomalacia
      (1). METHODS: Serum and CSF CRP and SAA were measured. Selection criteria
      included neurologic disease, antemortem diagnosis of EPM or CVSM, or postmortem
      diagnosis of EPM, CVSM, or other neurologic disease, and availability of
      serological results and archived samples for testing. RESULTS: Serum SAA and
      serum CRP levels were generally undetectable or low in horses with EPM (median
      CRP <=0.1 mg/L, <=0.1-14.4 mg/L; median SAA <=0.1 mg/L, <=0.1-6.11 mg/L) and CVSM
      (median CRP <=0.1, <=0.1-2.41 mg/L; median SAA <=0.1mg/L, <=0.1-13.88 mg/L). CSF
      CRP and SAA for horses with EPM (median CRP 3.35 mg/l, 0.19-13.43 mg/l; median
      SAA <=0.1 mg/L, <=0.1-2.4 mg/L) and CVSM (median CRP 4.015 mg/L, 0.16-9.62 mg/L;
      median SAA 0.62 mg/L, <=0.1-2.91 mg/L) were also undetectable or low. Kruskal
      Wallis test showed no statistically significant differences between serum CRP (P
      = .14), serum SAA (P = .79), spinal fluid CRP (P = .65), or spinal fluid SAA
      between horses with EPM and CVSM (P = .52). CONCLUSION: Neither SAA nor CRP in
      serum or CSF aid diagnosis of EPM.

PMID- 30216560
TI  - Presumptive non-cirrhotic bleeding esophageal varices in a dog.
AB  - An 8-year-old male American Staffordshire terrier was admitted for evaluation of
      chronic episodes of ptyalism and hematemesis after exercise. Abnormalities were
      not detected on routine clinicopathological tests, thoracic radiography, and
      abdominal ultrasonography. Endoscopic examination revealed a labyrinthine network
      of severely distended, hemorrhagic esophageal blood vessels. Computed tomography
      angiography demonstrated a network of para-esophageal vessels that communicated
      with the celiac artery caudally and the brachiocephalic trunk cranially,
      consistent with a diagnosis of non-cirrhotic esophageal varices. This is a report
      of exercise, ptyalism, and hematemesis secondary to presumptive, non-cirrhotic,
      bleeding esophageal varices in a dog.

PMID- 30216562
TI  - Solid Halide Electrolytes with High Lithium-Ion Conductivity for Application in 4
      V Class Bulk-Type All-Solid-State Batteries.
AB  - New lithium halide solid-electrolyte materials, Li3 YCl6 and Li3 YBr6 , are found
      to exhibit high lithium-ion conductivity, high deformability, and high chemical
      and electrochemical stability, which are required properties for all-solid-state
      battery (ASSB) applications, particularly for large-scale deployment. The lithium
      ion conductivities of cold-pressed powders surpass 1 mS cm-1 at room temperature
      without additional intergrain or grain boundary resistances. Bulk-type ASSB cells
      employing these new halide solid electrolyte materials exhibit coulombic
      efficiencies as high as 94% with an active cathode material of LiCoO2 without any
      extra coating. These superior electrochemical characteristics, as well as their
      material stability, indicate that lithium halide salts are another promising
      candidate for ASSB solid electrolytes in addition to sulfides or oxides.

PMID- 30216561
TI  - Echocardiographic evaluation of the right ventricular dimension and systolic
      function in dogs with pulmonary hypertension.
AB  - BACKGROUND: Right ventricular (RV) enlargement and dysfunction are associated
      with prognosis in humans with pulmonary hypertension (PH). HYPOTHESIS/OBJECTIVES:
      To assess RV size and systolic function in dogs with PH and to determine if they
      are associated with disease severity and right-sided congestive heart failure (R
      CHF). ANIMALS: 89 dogs with PH and 74 healthy dogs. METHODS: Prospective
      observational study. PH was classified according to the tricuspid regurgitation
      pressure gradient. RV end-diastolic area (RVEDA) index was calculated as RVEDA
      divided by body surface area. RV systolic function was assessed with the
      tricuspid annular plane systolic excursion (TAPSE) and the RV fractional area
      change (FAC) normalized for body weight (TAPSEn and FACn, respectively). RESULTS:
      RVEDA index was higher in dogs with moderate PH (10.8 cm2 /m2 ; range, 6.2-14.4
      cm2 /m2 ) and severe PH (12.4 cm2 /m2 ; range, 7.7-21.4 cm2 /m2 ) than in those
      with mild PH (8.4 cm2 /m2 ; range, 4.8-11.6 cm2 /m2 ) and control dogs (8.5 cm2
      /m2 ; range, 2.8-11.6 cm2 /m2 ; P < .001). RVEDA index was significantly higher
      in dogs with R-CHF (13.7 cm2 /m2 ; range, 11.0-21.4 cm2 /m2 ) than in dogs
      without R-CHF (9.4 cm2 /m2 ; range, 4.8-17.1 cm2 /m2 ; P < .001). The severity of
      tricuspid regurgitation (TR) was the only independent predictor of the RVEDA
      index (P < .001). TAPSEn and FACn were not significantly different among varying
      degrees of PH severity and between dogs with and without R-CHF. CONCLUSIONS AND
      CLINICAL IMPORTANCE: The RVEDA index can be used to evaluate RV size in dogs. It
      can provide additional information in dogs with PH and predict R-CHF. Severity of
      TR is the main determinant of RV enlargement in dogs with PH.

PMID- 30216563
TI  - Mechanochemically Assisted Synthesis of a Ru Catalyst for Hydrogen Evolution with
      Performance Superior to Pt in Both Acidic and Alkaline Media.
AB  - Catalysts are at the heart of the hydrogen evolution reaction (HER) for the
      production of pure and clean hydrogen. For practical applications, the scalable
      synthesis of efficient HER catalysts, which work in both acidic and alkaline
      media, is highly desired. In this work, the mechanochemically assisted synthesis
      of a Ru catalyst with HER performance surpassing Pt in both acidic and alkaline
      media is reported. Mass production of this Ru catalyst can be achieved via a two
      step procedure: the mechanochemical reaction between graphite and dry ice
      produces edge-carboxylic-acid-functionalized graphene nanoplatelets (CGnP);
      mixing a Ru precursor and the CGnP in an aqueous medium introduces Ru ions, which
      coordinate on the CGnP. Subsequent annealing results in uniform Ru nanoparticles
      (~2 nm) anchored on the GnP matrix (Ru@GnP). The efficient Ru@GnP catalyst can be
      easily powered by a single silicon solar cell using a wireless integration
      device. The self-powered device exhibits robust hydrogen evolution under the
      irradiation of standard AM 1.5 solar light. This work provides a new opportunity
      for the low-cost mass production of efficient and stable catalysts for practical
      applications.

PMID- 30216564
TI  - Pressure/Temperature Sensing Bimodal Electronic Skin with Stimulus
      Discriminability and Linear Sensitivity.
AB  - Human skin imperfectly discriminates between pressure and temperature stimuli
      under mixed stimulation, and exhibits nonlinear sensitivity to each stimulus.
      Despite great advances in the field of electronic skin (E-skin), the limitations
      of human skin have not previously been overcome. For the first time, the
      development of a stimulus-discriminating and linearly sensitive bimodal E-skin
      that can simultaneously detect and discriminate pressure and temperature stimuli
      in real time is reported. By introducing a novel device design and using a
      temperature-independent material, near-perfect stimulus discriminability is
      realized. In addition, the hierarchical contact behavior of the surface-wrinkled
      microstructure and the optimally reduced graphene oxide in the E-skin contribute
      to linear sensitivity to applied pressure/temperature stimuli over wide intensity
      range. The E-skin exhibits a linear and high pressure sensitivity of 0.7 kPa-1 up
      to 25 kPa. Its operation is also robust and exhibits fast response to pressure
      stimulus within 50 ms. In the case of temperature stimulus, the E-skin shows a
      linear and reproducible temperature coefficient of resistance of 0.83% K-1 in the
      temperature range 22-70  degrees C and fast response to temperature change within
      100 ms. In addition, two types of stimuli are simultaneously detected and
      discriminated in real time by only impedance measurements.

PMID- 30216565
TI  - A Ternary Ni46 Co40 Fe14 Nanoalloy-Based Oxygen Electrocatalyst for Highly
      Efficient Rechargeable Zinc-Air Batteries.
AB  - Replacing noble-metal-based oxygen reduction reaction (ORR) and oxygen evolution
      reaction (OER) electrocatalysts is the key to developing efficient Zn-air
      batteries (ZABs). Here, a homogeneous ternary Ni46 Co40 Fe14 nanoalloy with a
      size distribution of 30-60 nm dispersed in a carbon matrix (denoted as C@NCF-900)
      as a highly efficient bifunctional electrocatalyst produced via supercritical
      reaction and subsequent heat treatment at 900  degrees C is reported. Among all
      the transition-metal-based electrocatalysts, the C@NCF-900 exhibits the highest
      ORR performance in terms of half-wave potential (0.93 V) in 0.1 m KOH. Moreover,
      C@NCF-900 exhibits negligible activity decay after 10 000 voltage cycles with
      minor reduction (0.006 V). In ZABs, C@NCF-900 outperforms the mixture of Pt/C 20
      wt% and IrO2 , cycled over 100 h under 58% depth of discharge condition.
      Furthermore, density functional theory (DFT) calculations and in situ X-ray
      absorption spectroscopy strongly support the active sites and site-selective
      reaction as a plausible ORR/OER mechanism of C@NCF-900.

PMID- 30216566
TI  - Management of antipsychotic related hyperprolactinemia in older people: Can we
      extrapolate from existing guidance?

PMID- 30216567
TI  - Impact of 2-Ethylhexyl Stereoisomers on the Electrical Performance of Single
      Crystal Field-Effect Transistors.
AB  - Many organic semiconductors (OSCs) inherit chiral alkyl chains, which ensure the
      desirable high solubility for solution-processing but may also lead to disorder,
      inhomogeneous film-formation, as well as interfacial defects due to the presence
      of mixtures of stereoisomers or diastereomers, which impair their peak
      performance. Here, single-crystal field-effect transistors (SCFETs) of a
      diketopyrrolopyrrole-based organic semiconductor with chiral 2-ethylhexyl
      substituents by sublimation in air and organic ribbon mask method are fabricated.
      Devices of the mesomer (R/S), both enantiomers (R/R, S/S), as well as mixtures of
      these three stereoisomers measured under ambient conditions exhibit all
      appreciable p-channel charge carrier mobilities of > 0.1 cm2 V-1 s-1 despite
      different packing arrangement in the R/S, R/R (or S/S), and racemate crystal
      structures. These results suggest a surprising tolerance for isomeric impurities.
      The highest literature-reported p-channel mobility so far for a
      diketopyrrolopyrrole-based OSC of 3.4 cm2 V-1 s-1 (Ion /Ioff of 1 * 106 ) is,
      however, only obtained for the pure R/S mesomer, illustrating the inherent
      potential of stereochemical purity. These results on SCFETs are further
      substantiated by studies on organic thin-film transistors (OTFTs) of pure and
      mixed thin films of the different stereoisomers.

PMID- 30216568
TI  - Direct Chirality Recognition of Single-Crystalline and Single-Walled Transition
      Metal Oxide Nanotubes on Carbon Nanotube Templates.
AB  - Chirality is a significant structural feature for chemistry, biology, physics,
      and materials science, and especially determines the electrical, mechanical, and
      optical properties of diverse tubular structures, such as carbon nanotubes
      (CNTs). To recognize the chirality of nanotubes, templates are introduced as
      potential tools to obtain crystalline samples with visible chiral fringes under
      electron microscopes. However, few efforts show optimistic results, and new
      understanding is desired to control the sample quality with CNT templates. Here,
      a synthesis strategy of single-crystalline molybdenum trioxide (alpha-MoO3 )
      nanotubes (MONTs) on CNT surfaces is reported to build a 1D van der Waals (vdW)
      heterostructure. The chirality of the MONTs can be directly "seen" and their
      structural selectivity is revealed. First, the centralized distribution of the
      chiral angles of the MONTs indicates a preferential orientation due to the
      anisotropic bending rigidity of the 2D layers. Then, the interlayer mismatching
      rejects the radial stacking of alpha-MoO3 to maintain the single-walled nature.
      These results provide a spontaneous strategy for the efficient recognition and
      control of chirality, and open up a new avenue for CNT-based functional 1D vdW
      heterostructures.

PMID- 30216569
TI  - LncRNA TP73-AS1 predicts poor prognosis and functions as oncogenic lncRNA in
      osteosarcoma.
AB  - TP73 antisense RNA 1 (TP73-AS1), a novel long noncoding RNA (lncRNA), has been
      suggested to be deregulated in various human cancers and serve as a tumor
      suppressor or promoter, depending on tumor types. The role of TP73-AS1 in
      osteosarcoma is still unknown. In our results, TP73-AS1 was highly expressed in
      osteosarcoma tissue samples and cell lines compared with matching adjacent
      nontumor tissue specimens and a normal human osteoblast cell line, respectively.
      Moreover, high expression of TP73-AS1 was statistically associated with advanced
      Enneking stage, large tumor size, present distant metastasis, and poor
      histological grade, while exhibiting no statistical association with age, sex,
      and tumor site. The survival analyses showed that patients with osteosarcoma with
      high expression of TP73-AS1 obviously had lower overall survival than
      osteosarcoma patients with low expression of TP73-AS1, and high expression of
      TP73-AS1 was an independent poor prognostic factor for osteosarcoma patients. The
      experiments in vitro indicated that inhibition of TP73-AS1 expression depressed
      osteosarcoma cell viability, migration, and invasion, and arrested cell cycle. In
      conclusion, TP73-AS1 serves as oncogenic lncRNA participated in osteosarcoma
      progression.

PMID- 30216570
TI  - A Stabilized Bisphosphanylsilylene and Its Heavier Congeners.
AB  - A bisphosphanylsilylene with [3]ferrocenophane backbone and its heavier analogues
      are described in the form of donor adducts. These heterocarbenes can be formed by
      dehydrochlorination (Si) or cycloreversion (Sn, Pb) using NHC (N-heterocyclic
      carbene) tetramethylimidazol-2-ylidene. The structures of the bisphosphanyl
      silylene, -stannylene and -plumbylene NHC adducts are presented, and the bonding
      and stability of these compounds were elucidated using DFT calculations.
      Reactivity studies confirm the stability of the silylene adduct, where the
      electrophilic character of the silylene center is comparable to a borane.

PMID- 30216571
TI  - On Jeff =0 Ground State Iridates(V): Tracking Residual Paramagnetism in New Bi2
      NaIrO6.
AB  - Open-shell transition metal oxides are capable of developing a rich diversity of
      electronic phases. The specific features evolving crucially depend on an
      intricate interplay of various local and long-range electronic interactions.
      Recently, the 5d transition elements have come into sharp focus because for these
      elements spin-orbit coupling (SOC) and onsite Coulomb repulsion (U) are on a
      comparable energy scale. For Ir4+ the t2g level associated to an octahedral
      crystal field (CF) is split by SOC, giving rise to a Jeff = 1/2 spin state and
      rendering respective oxides like Sr2 IrO4 as Mott insulators. Transferring this
      scenario to iridium(V) oxides would lead to a diamagnetic ground state, Jeff =0.
      However, reported experimental results do not lend unambiguous support for such
      an electronic state. Theoretical explanations for the breakdown of the J=0
      magnetic state suffer from conspicuous discrepancies. In an attempt to
      empirically contribute to resolving the puzzle, Bi2 NaIrO6 was synthesized in
      high purity by precipitation from homogeneous solution; it represents an
      iridium(V) oxide where long range band structure effects and magnetic
      superexchange are minimized, and the t2g degeneracy is lifted geometrically. We
      managed to reduce the strength of paramagnetic response, lending support to a
      Jeff =0 ground state of Bi2 NaIrO6 , exhibiting van Vleck type behavior.

PMID- 30216572
TI  - Phosphorescent Cyclometalated Platinum(II) aNHC Complexes.
AB  - The synthesis and characterization of the first bidentate C^C* cyclometalated
      platinum(II) complexes based on abnormal N-heterocyclic carbenes (aNHC) is
      presented. The aNHC ligand precursors are prepared from benzonitriles and
      anilines to form 1,2,3-trisubstituted imidazolium salts. The title compounds were
      synthesized by in situ generation of the silver carbene complex, followed by
      transmetalation to platinum and subsequent introduction of the beta-diketonate
      ligand. Structural characterization by 2D NMR experiments, as well as solid-state
      structures unequivocally prove the abnormal binding mode of the aNHC ligands.
      Additionally, the photophysical properties of the platinum(II) complexes were
      examined and studied in detail by DFT calculations and cyclic voltammetry
      experiments. The title compounds proved to be strongly emissive at room
      temperature in the green to orange region of the visible spectrum, with emission
      efficiencies of up to 69 %.

PMID- 30216574
TI  - The role of the Synechocystis sp. PCC 6803 homolog of the circadian clock output
      regulator RpaA in day-night transitions.
AB  - Cyanobacteria exhibit rhythmic gene expression with a period length of 24 hours
      to adapt to daily environmental changes. In the model organism
      Synechococcuselongatus PCC 7942, the central oscillator consists of the three
      proteins KaiA, KaiB and KaiC and utilizes the histidine kinase SasA and its
      response regulator RpaA as output-signaling pathway. Synechocystis sp. PCC 6803
      contains in addition to the canonical kaiAB1C1 gene cluster two further homologs
      of the kaiB and kaiC genes. Here, we demonstrate that the SasA-RpaA system
      interacts with the KaiAB1C1 core oscillator only. Interaction with KaiC2 and
      KaiC3 proteins was not detected, suggesting different signal transduction
      components for the clock homologs. Inactivation of rpaA in Synechocystis sp. PCC
      6803 leads to reduced viability of the mutant in light-dark cycles, especially
      under mixotrophic growth conditions. Chemoheterotrophic growth of the ?rpaA
      strain in the dark was abolished completely. Transcriptomic data revealed that
      RpaA is mainly involved in the regulation of genes related to CO2 - acclimation
      in the light and to carbon metabolism in the dark. Further, our results indicate
      a link between the circadian clock and phototaxis.

PMID- 30216573
TI  - A Novel Strategy for Scalable High-Efficiency Planar Perovskite Solar Cells with
      New Precursors and Cation Displacement Approach.
AB  - Methylammonium iodide (MAI) and lead iodide (PbI2 ) have been extensively
      employed as precursors for solution-processed MAPbI3 perovskite solar cells
      (PSCs). However, the MAPbI3 perovskite films directly deposited from the
      precursor solutions, usually suffer from poor surface coverage due to
      uncontrolled nucleation and crystal growth of the perovskite during the film
      formation, resulting in low photovoltaic conversion efficiency and poor
      reproducibility. Herein, propylammonium iodide and PbI2 are employed as
      precursors for solution deposition of propylammonium lead iodide (PAPbI3 )
      perovskite film. It is found that the precursors have good film formability,
      enabling the deposition of a large-area and homogeneous PAPbI3 perovskite film by
      a scalable dip-coating technique. The dip-coated PAPbI3 film is then subjected to
      an organic-cation displacement reaction, resulting in MAPbI3 film with high
      surface coverage and crystallinity. With the MAPbI3 film as the light absorber,
      planar PSCs are fabricated, and stabilized power conversion efficiencies of
      19.27% and 15.68% can be achieved for the devices with active areas of 0.09 and
      5.02 cm2 , respectively. The technology reported here provides a robust and
      efficient approach to fabricate large-area and high-efficiency perovskite cells
      for practical application.

PMID- 30216575
TI  - Structural and Electronic Responses to the Three Redox Levels of Fe(NO)N2 S2 
      Fe(NO)2.
AB  - The nitrosylated diiron complexes, Fe2 (NO)3 , of this study are interpreted as a
      mono-nitrosyl Fe(NO) unit, MNIU, within an N2 S2 ligand field that serves as a
      metallodithiolate ligand to a dinitrosyl iron unit, DNIU. The cationic Fe(NO)N2
      S2 ?Fe(NO)2 + complex, 1+ , of Enemark-Feltham electronic notation {Fe(NO)}7 
      {Fe(NO)2 }9 , is readily obtained via myriad synthetic routes, and shown to be
      spin coupled and diamagnetic. Its singly and doubly reduced forms, {Fe(NO)}7 
      {Fe(NO)2 }10 , 10 , and {Fe(NO)}8 -{Fe(NO)2 }10 , 1- , were isolated and
      characterized. While structural parameters of the DNIU are largely unaffected by
      redox levels, the MNIU readily responds; the neutral, S= 1/2 , complex, 10 ,
      finds the extra electron density added into the DNIU affects the adjacent MNIU as
      seen by the decrease its Fe-N-O angle (from 171 degrees  to 149 degrees ). In
      contrast, addition of the second electron, now into the MNIU, returns the Fe-N-O
      angle to 171 degrees  in 1- . Compensating shifts in FeMNIU distances from the N2
      S2 plane (from 0.518 to 0.551 to 0.851 A) contribute to the stability of the
      bimetallic complex. These features are addressed by computational studies which
      indicate that the MNIU in 1- is a triplet-state {Fe(NO)}8 with strong spin
      polarization in the more linear FeNO unit. Magnetic susceptibility and parallel
      mode EPR results are consistent with the triplet state assignment.

PMID- 30216576
TI  - Comparison of gas chromatography/quadrupole time-of-flight and quadrupole
      Orbitrap mass spectrometry in anti-doping analysis: I. Detection of anabolic
      androgenic steroids.
AB  - RATIONALE: The World Anti-Doping Agency (WADA) encourages drug-testing
      laboratories to develop screening methods that can detect as many doping
      substances as possible in urine. The use of full-scan high-resolution acquisition
      (FS/HR) with gas chromatography/mass spectrometry (GC/MS) for the detection of
      known and unknown trimethylsilyl (TMS) derivatives of anabolic-androgenic
      steroids (AAS) provides anti-doping testing bodies with a new analytical tool.
      METHODS: The AAS were extracted from urine samples by generic liquid-liquid
      extraction, after enzymatic hydrolysis, and TMS derivatization. The extracted
      urine was analyzed by GC/Q-TOF and GC/Q-Orbitrap to compare the performance of
      the two instrument types for the detection of 46 AAS in human urine. The
      quantitation of endogenous anabolic steroids and the ability of the two
      analytical platforms to comply with the requirements for testing as part of the
      WADA Athlete Biological Passport (ABP) were also assessed. RESULTS: The data
      presented show that the analytical performance for both instruments complies with
      the WADA specifications. The limits of detection (LODs) for both instruments are
      well below the WADA 50% Minimum Required Performance Levels. The mass errors in
      the current study for the GC/Q-Orbitrap platform are lower than those obtained
      for the GC/Q-TOF instrument. CONCLUSIONS: The data presented herein proved that
      both molecular profiling platforms can be used for antidoping screening. The mass
      accuracies are excellent in both instruments; however, the GC/Q-Orbitrap performs
      better as it provides higher resolution than the GC/Q-TOF platform.

PMID- 30216577
TI  - Variability of the cortisol awakening response and morning salivary oxytocin in
      late adolescence.
AB  - Exogenously administered oxytocin interacts with the hypothalamic-pituitary
      adrenal (HPA) axis to modulate endogenous cortisol levels, suggesting a
      synergistic role for these two hormones in the response to stress, cognitive
      performance and the development of psycho-behavioural disorders. The cortisol
      awakening response (CAR) is considered a reliable measure of HPA axis function in
      humans. However, the CAR appears to vary considerably from day to day and may be
      strongly influenced by the anticipated demands of the day ahead. The level of
      variation intrinsic to the CAR is unclear because few studies have examined the
      CAR in the absence of daily environmental variation. It is not known whether
      oxytocin has a similar or complementary awakening response. Therefore, over three
      consecutive days, we examined 12 adolescents (aged 15-17 years) in a highly
      controlled sleep laboratory. Saliva was collected on days 4-6 of a 9-day
      laboratory visit. Cortisol and oxytocin levels were determined by an enzyme
      linked immunosorbent assay from saliva sampled at 0, 15, 30 and 45 minutes, and 8
      and 12 hours post-awakening. CAR magnitude varied between days and was associated
      with sleep duration and pre-awakening sleep stage. Conversely, oxytocin levels
      dropped dramatically in the first 15 minutes post-awakening and were highly
      consistent across participants and days. Older participants had higher awakening
      oxytocin concentrations. Although cortisol increases and oxytocin rapidly
      declines upon awakening, their diurnal variation does not appear to be related at
      basal, peripheral levels, consistent with a previous finding that exogenously
      administered oxytocin only modulates cortisol under conditions of stress.

PMID- 30216578
TI  - Visible-Light-Mediated Liberation and In Situ Conversion of Fluorophosgene.
AB  - The first example for the photocatalytic generation of a highly electrophilic
      intermediate that is not based on radical reactivity is reported. The single
      electron reduction of bench-stable and commercially available 4
      (trifluoromethoxy)benzonitrile by an organic photosensitizer leads to its
      fragmentation into fluorophosgene and benzonitrile. The in situ generated
      fluorophosgene was used for the preparation of carbonates, carbamates, and urea
      derivatives in moderate to excellent yields via an intramolecular cyclization
      reaction. Transient spectroscopic investigations suggest the formation of a
      catalyst charge-transfer complex-dimer as the catalytic active species.
      Fluorophosgene as a highly reactive intermediate, was indirectly detected via its
      next downstream carbonyl fluoride intermediate by NMR. Furthermore, detailed NMR
      analyses provided a comprehensive reaction mechanism including a water dependent
      off-cycle equilibrium.

PMID- 30216580
TI  - Synthesis of Ribo-Azanucleosides by Anodic Oxidation: Reactivity Control of
      Intermediate for Efficient Access to Pharmacophores.
AB  - Azanucleosides, the sugar-modified nucleoside analogues, have various biological
      activities, while their efficient synthetic strategy is still under development.
      Herein, a novel method for the synthesis of pharmaceutically relevant
      azanucleosides, beta-anomers of ribo-azanucleosides, by means of site-specific
      anodic C-H activation by using a nitroalkane-lithium perchlorate medium is
      reported. A mechanistic study of the electrochemical reaction and the
      armed/disarmed concept from traditional glycochemistry revealed that the 2'
      substituent has a significant effect on the reactivity of prolinol derivative,
      and suitable carboxylic acid additives can control the reactivity of the
      intermediate species, an iminium cation equivalent. Finally, this method was
      demonstrated to be applicable for the synthesis of beta-anomers of ribo
      azanucleosides with all four nucleobases in a stereoselective manner.

PMID- 30216581
TI  - Tubulin heterogeneity and spatial arrangement of the mouse meiotic spindle.

PMID- 30216579
TI  - Evaluation of point-of-care thoracic ultrasound and NT-proBNP for the diagnosis
      of congestive heart failure in cats with respiratory distress.
AB  - BACKGROUND: The diagnosis of congestive heart failure (CHF) in cats is
      challenging. Point-of-care (POC) thoracic ultrasound and NT-proBNP testing are
      emerging tools that may aid in diagnosis. HYPOTHESIS/OBJECTIVES: To assess the
      diagnostic accuracy of POC lung ultrasound (LUS), focused cardiac ultrasound
      (FCU), and NT-proBNP in predicting a final diagnosis of CHF. ANIMALS: Fifty-one
      cats in respiratory distress. METHODS: Blood NT-proBNP, LUS, and FCU evaluating
      left atrial (LA) size and presence of pericardial effusion (PCEFF) were performed
      in all cats. Lung ultrasound findings including pleural effusion (PLEFF), number
      of B-lines, and sub-pleural abnormalities were noted. Medical records were
      evaluated for final diagnosis. RESULTS: Thirty-three of 51 (65%) cats were
      diagnosed with CHF. Lung ultrasound and blood NT-proBNP were significant
      predictors of CHF in a multivariate model. The LUS criterion that maximized
      accuracy for CHF diagnosis was presence of >1 site strongly positive for B-lines
      (>3 B-lines per site), resulting in sensitivity of 78.8%, specificity of 83.3%,
      and area under the curve (AUC) of 0.833. Subjective LA enlargement was 97.0%
      sensitive and 100% specific for CHF (AUC 0.985). Presence of PCEFF also was 100%
      specific, but only 60.6% sensitive, for CHF (AUC 0.803). A positive blood NT
      proBNP test was 93.9% sensitive and 72.2% specific for the diagnosis of CHF (AUC
      0.831). CONCLUSIONS AND CLINICAL IMPORTANCE: Point-of-care diagnostic techniques
      of LUS, FCU, and NT-proBNP are useful to diagnose CHF in cats with respiratory
      distress.

PMID- 30216582
TI  - Upregulation of HB-EGF, Msx.1, and miRNA Let-7a by administration of calcitonin
      through mTOR and ERK1/2 pathways during a window of implantation in mice.
AB  - BACKGROUND: Successful implantation of embryos requires endometrial receptivity.
      Calcitonin is one of the factors influencing the implantation window. This study
      aimed to evaluate calcitonin effects on endometrial receptivity. To this end, the
      effects of calcitonin on the implantation window in the ovarian stimulation and
      the normal ovarian cycle were investigated by the morphological study of the
      endometrium as well as the expression of MSX.1, HB-EGF, and micro-RNA (miRNA) Let
      7a; then the mechanisms of calcitonin effects were studied through the mammalian
      target of rapamycin (mTOR) and extracellular signal-regulated kinase 1/2 (ERK1/2)
      signaling pathways. MATERIALS AND METHODS: A total of 64 Bulb/c mice were divided
      into two groups: Normal ovarian cycle and ovarian stimulation. Each group
      consisted of four subgroups: Ctrl, CT, PP242, and CT + PP242. Calcitonin and
      PP242 were injected on the fourth day of pregnancy and 24 hr later all the mice
      were killed. Uterine tissue samples were used for morphological analysis and the
      endometrial epithelial and the stromal cells were isolated from myometrium for
      evaluation of gene and protein expression. RESULTS: Ovarian stimulation increased
      the phosphorylation levels of mTOR and ERK1/2 and the expression of miRNA Let-7a.
      Calcitonin injection increased the expression of HB-EGF, Msx.1, and miRNA Let-7a
      in a normal ovarian cycle and in ovarian-stimulated mice. It also increased
      eukaryotic initiation factor 4E-binding protein 1 and ERK1/2 phosphorylation in
      normal ovarian cycles. CONCLUSION: Calcitonin improved the receptivity of the
      uterine endometrium by upregulation of the HB-EGF, Msx.1, and miRNA Let-7a likely
      through mTOR and ERK1/2 signaling pathway.

PMID- 30216583
TI  - Quantitative NMR analysis of L-Dopa in seeds from two varieties of Mucuna
      pruriens.
AB  - INTRODUCTION: L-Dopa, a key neurotransmitter used to treat neural disorders such
      as Parkinson's disease, is found in the seeds of the genus Mucuna at a sufficient
      concentration for possible commercial use. OBJECTIVE: To develop a simple and
      reliable method to extract L-Dopa from M. pruriens seeds in an aqueous medium and
      then quantitate this compound using a 1 H qNMR method (internal standard); and
      also to evaluate the accuracy and reproducibility of this method with an NMR
      calibration curve. METHODOLOGY: The extraction method of L-Dopa from M. pruriens
      was optimized. The quantitation with single point quantitative NMR (qNMR) and NMR
      calibration curve was based on the resonance properties of the main functional
      groups of the L-Dopa molecule, in particular the signals of the three aromatic
      protons, which were compared with the signal of an internal standard such as
      syringic acid. The accuracy (precision and trueness) and reproducibility of both
      NMR techniques were evaluated. RESULTS: The methods of single point qNMR and NMR
      calibration curve, applied to the seeds of two M. pruriens varieties, gave very
      similar L-Dopa contents: 3.0-3.2% and 3.0-3.1%, respectively. CONCLUSION: The
      statistical analysis confirmed the accuracy and reproducibility of this single
      point qNMR method (internal standard) for determining L-Dopa, as well as other
      commercial preparations of this species, without performing an NMR calibration
      curve.

PMID- 30216584
TI  - Cyclodextrin-Based Macromolecular Systems as Cholesterol-Mopping Therapeutic
      Agents in Niemann-Pick Disease Type C.
AB  - Over the last decade, cyclodextrins (CDs) have gained considerable attention as a
      potential therapeutic intervention in the treatment of the rare genetic condition
      Niemann-Pick type C disease (NPC). However, the oligosaccharide in its monomeric
      form suffers from serious side effects, especially from a pharmacokinetic and
      biodistribution standpoint. CD-based macromolecular systems hold great promise to
      overcome such limitations and might provide an improved therapeutic approach in
      reducing cholesterol accumulation in NPC. In the present article, the latest
      developments and synthetic strategies in the preparation of CD-containing
      polymers as cholesterol-mopping therapeutic agents in NPC are summarized.

PMID- 30216585
TI  - The influence of voltage-gated sodium channels on human gastrointestinal
      nociception.
AB  - BACKGROUND: Abdominal pain is a frequent and persistent problem in the most
      common gastrointestinal disorders, including irritable bowel syndrome and
      inflammatory bowel disease. Pain adversely impacts quality of life, incurs
      significant healthcare expenditures, and remains a challenging issue to manage
      with few safe therapeutic options currently available. It is imperative that new
      methods are developed for identifying and treating this symptom. A variety of
      peripherally active neuroendocrine signaling elements have the capability to
      influence gastrointestinal pain perception. A large and growing body of evidence
      suggests that voltage-gated sodium channels (VGSCs) play a critical role in the
      development and modulation of nociceptive signaling associated with the gut.
      Several VGSC isoforms demonstrate significant promise as potential targets for
      improved diagnosis and treatment of gut-based disorders associated with hyper-
      and hyposensitivity to abdominal pain. PURPOSE: In this article, we critically
      review key investigations that have evaluated the potential role that VGSCs play
      in visceral nociception and discuss recent advances related to this topic.
      Specifically, we discuss the following: (a) what is known about the structure and
      basic function of VGSCs, (b) the role that each VGSC plays in gut nociception,
      particularly as it relates to human physiology, and (c) potential diagnostic and
      therapeutic uses of VGSCs to manage disorders associated with chronic abdominal
      pain.

PMID- 30216586
TI  - Extrinsic and intrinsic constraints interact to drive extra-pair paternities in
      the Alpine marmot.
AB  - To reproduce, animals have to form pairs and large variations in the degree of
      mate switching are observed. Extrinsic and intrinsic factors can constrain
      individual's mate switching. Among intrinsic factors, genes involved in pair
      bonding, such as Avpr-1a, receive increasing attention. The length of
      microsatellites present in the regulatory region of Avpr-1a determines the neural
      densities and distributions of the vasopressin receptors known to impact pair
      bonding behaviours. For the first time, we investigated whether and how the
      genetic makeup at Avpr-1a, an intrinsic factor, and the social context, an
      extrinsic factor, experienced by wild Alpine marmot (Marmota marmota) females
      affect the proportion of extra-pair young. This proportion was positively
      correlated with the length of their Avpr-1a regulatory region but only when the
      social constraints were relaxed, that is when mature male subordinates were
      present. When ignoring the interactive effect between the length of their Avpr-1a
      regulatory region and the social constraints, the genetic makeup at Avpr-1a was
      not associated with the proportion of extra-pair young. Under natural conditions,
      the genetic regulation of pair-bonding could be hidden by extrinsic factors
      constraining mate choice.

PMID- 30216587
TI  - Lead-Free Highly Efficient Blue-Emitting Cs3 Cu2 I5 with 0D Electronic Structure.
AB  - Halide perovskites, including CsPbX3 (X = Cl, Br, I), have gained much attention
      in the field of optoelectronics. However, the toxicity of Pb and the low
      photoluminescence quantum yield (PLQY) of these perovskites hamper their use. In
      this work, new halide materials that meet the requirements of: (i) nontoxicity,
      (ii) high PLQY, and (iii) ease of fabrication of thin films via the solution
      process are explored. In particular, copper(I) halide compounds with low
      dimensional electronic structures are considered. Cs3 Cu2 I5 has a 0D photoactive
      site and exhibits blue emission (~445 nm) with very high PLQYs of ~90 and ~60%
      for single crystals and thin films, respectively. The large exciton binding
      energy of ~490 meV explains well the 0D electronic nature of Cs3 Cu2 I5 . Blue
      electroluminescence of Pb-free halides is demonstrated using solution-derived Cs3
      Cu2 I5 thin films.

PMID- 30216588
TI  - Polymerization-Induced Self-Assembly for Artificial Biology: Opportunities and
      Challenges.
AB  - The study of the origin of life and current undergoing efforts to produce
      artificial chemical systems mimicking the behavior of natural living systems have
      emerged as a hot topic at the interfaces among disciplines. In these two
      problems, the spontaneous generation of free-energy gradients by means of
      material interfaces plays a central role and, until recently, hindered progress.
      Polymerization-induced self-assembly (PISA) is a promising strategy for the
      formation of polymeric vesicles from a homogeneous mixture which, in the form of
      artificial biology, may reflect and inform the generation of vesicular structures
      in primitive Earth. In the past few years, PISA has been used for the
      construction of biomimetic vesicles or artificial protocells in artificial
      biology. These not only give inspiration for decoding some aspects of the origin
      of life in arbitrary environments but also offer potential for building
      innovative functional systems with a wide variety of applications. In this
      review, a brief summary of some of the unique possibilities offered by PISA and
      the development of PISA in exploration of artificial biology is provided, while
      some of the allied current challenges, limitations, and opportunities in this
      exciting field are highlighted.

PMID- 30216589
TI  - The Swedish systematic review of traumatic shaking is not flawed and should not
      be ignored.

PMID- 30216590
TI  - A Bayesian multivariate approach to estimating the prevalence of a superordinate
      category of disorders.
AB  - OBJECTIVE: Epidemiological research plays an important role in public health,
      facilitated by the meta-analytic aggregation of epidemiological trials into a
      single, more powerful estimate. This form of aggregation is complicated when
      estimating the prevalence of a superordinate category of disorders (e.g., "any
      anxiety disorder," "any cardiac disorder") because epidemiological studies rarely
      include all of the disorders selected to define the superordinate category. In
      this paper, we suggest that estimating the prevalence of a superordinate category
      based on studies with differing operationalization of that category (in the form
      of different disorders measured) is both common and ill-advised. Our objective is
      to provide a better approach. METHODS: We propose a multivariate method using
      individual disorder prevalences to produce a fully Bayesian estimate of the
      probability of having one or more of those disorders. We validate this approach
      using a recent case study and parameter recovery simulations. RESULTS: Our
      approach produced less biased and more reliable estimates than other common
      approaches, which were at times highly biased. CONCLUSION: Although our approach
      entails additional effort (e.g., contacting authors for individual participant
      data), the improved accuracy of the prevalence estimates obtained is significant
      and therefore recommended.

PMID- 30216591
TI  - Diagnosis of Li-Fraumeni Syndrome: Differentiating TP53 germline mutations from
      clonal hematopoiesis: Results of the observational AGO-TR1 trial.
AB  - The Li-Fraumeni cancer predisposition syndrome (LFS1) presents with a variety of
      tumor types and the TP53 gene is covered by most diagnostic cancer gene panels.
      We demonstrate that deleterious TP53 variants identified in blood-derived DNA of
      523 patients with ovarian cancer (AGO-TR1 trial) were not causal for the
      patients' ovarian cancer in three out of six TP53-positive cases. In three out of
      six patients, deleterious TP53 mutations were identified with low variant
      fractions in blood-derived DNA but not in the tumor of the patient seeking
      advice. The analysis of the TP53 and PPM1D genes, both intimately involved in
      chemotherapy-induced and/or age-related clonal hematopoiesis (CH), in 523
      patients and 1,053 age-matched female control individuals revealed that CH
      represents a frequent event following chemotherapy, affecting 26 of the 523
      patients enrolled (5.0%). Considering that TP53 mutations may arise from
      chemotherapy-induced CH, our findings help to avoid false-positive genetic
      diagnoses of LFS1.

PMID- 30216593
TI  - Recalling Lashley and Reconsolidating Hebb.
AB  - Many of the foundational theoretical ideas in the field of learning and memory
      are traced to Donald Hebb. Examination of these ideas and their evolution suggest
      that Karl Lashley might have significantly influenced their development. Here, we
      discuss the relationship between Hebb and Lashley, and the parallels between
      them. Many now investigating the neurobiological basis of memory may be unaware
      both of Hebb's original descriptions, and the likely substantial contributions of
      Lashley. Many of their concerns remain with us today, and by clarifying the
      history we hope to strengthen the foundations of our field. This article is
      protected by copyright. All rights reserved.

PMID- 30216592
TI  - Comparative mutational evaluation of multiple lung cancers by multiplex oncogene
      mutation analysis.
AB  - In patients presenting with synchronous or metachronous multiple lung cancer
      (MLC), it is important to distinguish between multiple primary lung cancer (MP)
      and intrapulmonary metastasis (IM). The present study was aimed at investigating
      the mutational profiles of synchronous/metachronous MLC and to compare the
      classification of paired tumors by multiplex gene mutation analysis with the
      histopathological evaluation. We carried out targeted sequencing of 20 lung
      cancer-related oncogenes using next-generation sequencing (NGS) in 82 tumors from
      37 MLC patients who underwent surgical resection at our department. The patients
      were diagnosed as MP or IM cases based on the Martini and Melamed criteria,
      histopathological and gene mutational evaluations. Matching mutations between
      paired tumors was observed in 20 (54%) patients, who were diagnosed as IM cases
      by mutational evaluation. Patients who could not be clearly diagnosed by
      histopathological evaluation were classified as equivocal cases. Among the
      histopathological IM cases (n = 7), six (86%) were confirmed as IM cases also by
      mutational evaluation, and most of the paired tumors of these cases (n = 5)
      harbored multiple matching mutations. Among the histopathological MP cases (n =
      17), mutational evaluation yielded a discordant diagnosis in eight (47%) cases.
      Of these, the paired tumors of four cases harbored multiple matching mutations,
      suggesting that the mutational diagnosis might be more suitable in these
      patients. Our findings suggest that multiplex mutational analysis could be a
      useful complementary tool for distinguishing between MP and IM in addition to
      histopathological evaluation.

PMID- 30216594
TI  - Barriers to psychosocial oncology service utilization in patients newly diagnosed
      with head and neck cancer.
AB  - OBJECTIVES: While patients with head and neck cancer (HNC) are known to
      experience higher levels of anxiety and depression, they do not always use
      psychosocial oncology (PSO) services when available. This study aimed to
      investigate barriers to PSO service utilization in this patient population, with
      the goal of appropriately targeting outreach interventions. METHODS: A conceptual
      model based on the Behavioral Model of Health Services Use was tested in 84
      patients newly diagnosed with a first occurrence of HNC followed longitudinally
      over 1 year, including variables collected through self-administered
      questionnaires, Structured Clinical Interviews for DSM (SCID-I), and medical
      chart reviews. RESULTS: Within the first-year post-diagnosis, 42.9% of HNC
      patients experienced clinical levels of psychological distress, with only 50% of
      these consulting PSO services (29% total). A logistic regression indicated that
      PSO utilization was increased when patients presented with advanced cancer (P =
      0.04) and a SCID-I diagnosis of major depressive disorder, anxiety disorder, or
      substance use disorder (P = 0.02), while there was an inverse relationship with
      self-stigma of seeking help (P = 0.03); these variables together successfully
      predicted 76.3% of overall PSO utilization, including 90.6% of non-users.
      CONCLUSIONS: Future outreach interventions in patients with HNC could address
      stigma in an attempt to enhance PSO integration into routine clinical care.

PMID- 30216595
TI  - Limited self-control and longevity.
AB  - This paper proposes a new framework to discuss self-control problems in the
      context of life-cycle health and longevity. Individual decisions are
      conceptualized as the partial control of impulsive desires of a short-run self by
      a rationally forward-looking long-run self. The short-run self strives for
      immediate gratification through consumption of health-neutral and unhealthy
      goods. The long-run self reflects the long-term consequences of unhealthy
      behavior on health outcomes and longevity and invests time and money to improve
      current and future health. The model is calibrated with data from the United
      States and used to provide an assessment of the impact of imperfect self-control
      on unhealthy consumption, health investments, lifetime health, and the age at
      death.

PMID- 30216596
TI  - Gastric motor and sensory function in health assessed by magnetic resonance
      imaging: Establishment of reference intervals for the Nottingham test meal in
      healthy subjects.
AB  - BACKGROUND: Current investigations of gastric emptying rarely identify the cause
      of symptoms or provide a definitive diagnosis in patients with dyspepsia. This
      study assessed gastric function by magnetic resonance imaging (MRI) using the
      modular "Nottingham test meal" (NTM) in healthy volunteers (HVs). METHODS: The
      NTM comprises (a) 400 mL liquid nutrient (0.75 kcal/mL) labeled with Gadolinium
      DOTA and (b) an optional solid component (12 agar-beads [0 kcal]). Filling
      sensations were documented. MRI measurements of gastric volume, emptying,
      contraction wave frequency, and secretion were obtained using validated methods.
      KEY RESULTS: Gastric function was measured in a population of 73 HVs stratified
      for age and sex. NTM induced moderate satiety and fullness. Labeled fluid was
      observed in the small bowel in all subjects after meal ingestion ("early-phase"
      GE). Secretion was rapid such that postprandial gastric content volume was often
      greater than meal volume (GCV0 > 400 mL), and there was increasing dilution of
      the meal during the study (P < 0.001). Gastric half-time was median 66-minutes
      (95% reference interval 35 to 161-minutes ["late-phase" GE]). The number of
      intact agar beads in the stomach was 7/12 (58%) at 60-minutes and 1/12 (8%) at
      120-minutes. Age, bodyweight and sex had measurable effects on gastric function;
      however, these were small compared to inter-individual variation for most
      metrics. CONCLUSIONS AND INFERENCES: Reference intervals are presented for MRI
      measurements of gastric function assessed for the mixed liquid/solid NTM. Studies
      in patients will determine which metrics are of clinical value and also whether
      the reference intervals presented here offer optimal diagnostic sensitivity and
      specificity.

PMID- 30216597
TI  - A new risk stratification score for the management of ultrasound-detected B3
      breast lesions.
AB  - To develop a predictive scoring system for ultrasound-detected B3 lesions at
      ultrasound-guided core needle biopsy (US-CNB). A total of 2724 consecutive US
      CNBs performed in our Institution (January 2011 to December 2014) were
      retrospectively reviewed. Inclusion criteria were as follows: (a)
      histopathological examination of the entire lesion or (b) availability of
      radiologic follow-up (FUP) >=24 months. Patient- and lesion-related variables
      patients' age, lesion consistency, lesion size, vascularization, BI-RADS
      category, and US-CNB result-were analyzed. Positive predictive values (PPVs) for
      malignancy were calculated correlating US-CNB results with excision histology or
      FUP. A scoring system for underlying malignancy was developed using risk factors
      weighting. A total of 102 B3 lesions were included: 27 atypical ductal
      hyperplasia (26.5%), 5 lobular intraepithelial neoplasia (4.9%), 32 radial scar
      (31.4%), 37 papillary lesions (36.3%), and 1 fibroepithelial lesion (0.9%).
      Surgery was performed on 71/102 (69.6%) lesions, and 22/71 were malignant; the
      remaining 31/102 lesions (30.4%) were unchanged at FUP. The overall PPV for
      malignancy was 21.6%. Patients' age (odds ratio [OR] = 3.63, P = 0.008), lesion
      consistency (OR = 5.96, P = 0.001), BI-RADS category (OR = 17.52, P < 0.001), and
      CNB result (OR = 3.6, P = 0.008) were associated with a higher risk of malignancy
      underestimation and selected as risk factors in the score definition. Two risk
      groups were identified: low (0-2 points) and high risk (3-5 points), with
      significantly different risk of malignancy underestimation (8.0% vs 59.3%, P <
      0.001). The proposed score helps to predict the risk of malignancy
      underestimation and choose the management of B3 lesions at US-CNB.

PMID- 30216598
TI  - Nipple-sparing mastectomy with periareolar incision and two-stage reconstruction:
      Initial analysis of 31 cases.
AB  - Surgical treatment of breast cancer has changed considerably over the past four
      decades, culminating in the substitution of conservative approaches for Halsted's
      paradigm from 1894. In parallel, many breast reconstruction techniques have been
      proposed for patients requiring mastectomy with loss of the nipple-areola complex
      (NAC). Myocutaneous flaps were once the most common form of reconstruction, but
      recently the use of implants and nipple-sparing mastectomy (NSM) in one or two
      stages has gained popularity. In this descriptive and cross-sectional study, we
      evaluated a sample of 31 NSM procedures with periareolar incision and two-stage
      reconstruction (tissue expander followed by implant) conducted between 2013 and
      2017, with emphasis on the rate of complications after at least 3 months of
      follow-up, local disease control and cosmesis measured on the Harvard scale. Five
      complications (16%) were observed, all of which related to the first stage:
      seroma (n = 1; 3.2%), treated with needle aspiration, NAC necrosis (n = 3; 9.6%),
      one case of which required debridement, and dehiscence (n = 1; 3.2%), treated
      with resuture. Cosmesis was classified as excellent by the surgeon in 96.8% (n =
      27). At the time of writing, no local recurrence had been observed. In
      conclusion, NSM with periareolar incision and two-stage reconstruction was found
      to be technically feasible and associated with few complications and satisfactory
      esthetic outcomes.

PMID- 30216599
TI  - SMARCB-1 deficient squamous cell carcinoma of a mediastinal cyst.
AB  - SMARCB1-deficiency has been found in a variety of tumors. Here, we report a
      SMARCB1-deficient squamous cell carcinoma of a mediastinal cyst. A 53-year-old
      man was diagnosed with a cyst of the pericardial region in his twenties. As a
      symptom at this time, he complained of severe pain and dyspnea in the right
      chest. Following investigation using imaging and histological examination of the
      biopsy specimen, he was diagnosed with a SMARCB1 deficient malignant neoplasm. As
      tumor cells showed positive immunostaining for p40 and CK5/6, the immunophenotype
      of the tumor was consistent with squamous cell carcinoma (SCC). The patient died
      six months after initial presentation. The autopsy showed the most part of the
      tumor with anaplastic cytomorphology, loss of SMARCB1, diffusely positive
      immunostaining for pancytokeratin, and negative immunostaining for p40 and CK5/6.
      To our knowledge, this is the first report of SMARCB1-deficient SCC of
      mediastinal cyst.

PMID- 30216601
TI  - Travelers' tropical skin diseases: Challenges and interventions.
AB  - Tropical regions receive a significant part of the traveling population. It is
      very important that health professionals are familiar with the main tropical skin
      diseases and able to advice patients appropriately. This article reviews the main
      tropical diseases of travelers, with an emphasis on diagnosis, management, and
      prevention. Among others, cutaneous larva migrans, myiasis, tungiasis, Chagas
      disease, Dengue fever, African trypanosomiasis, filariasis, and leishmaniasis are
      discussed. Increasing awareness among travelers and health care professionals can
      help reduce morbidity and mortality. Continued research on new drugs and vaccines
      is needed to reduce the risks of tropical diseases.

PMID- 30216600
TI  - Second rate or a second chance? Assessing biomass and biodiversity recovery in
      regenerating Amazonian forests.
AB  - Secondary forests (SFs) regenerating on previously deforested land account for
      large, expanding areas of tropical forest cover. Given that tropical forests rank
      among Earth's most important reservoirs of carbon and biodiversity, SFs play an
      increasingly pivotal role in the carbon cycle and as potential habitat for forest
      biota. Nevertheless, their capacity to regain the biotic attributes of
      undisturbed primary forests (UPFs) remains poorly understood. Here, we provide a
      comprehensive assessment of SF recovery, using extensive tropical biodiversity,
      biomass, and environmental datasets. These data, collected in 59 naturally
      regenerating SFs and 30 co-located UPFs in the eastern Amazon, cover >1,600 large
      and small-stemmed plant, bird, and dung beetles species and a suite of forest
      structure, landscape context, and topoedaphic predictors. After up to 40 years of
      regeneration, the SFs we surveyed showed a high degree of biodiversity
      resilience, recovering, on average among taxa, 88% and 85% mean UPF species
      richness and composition, respectively. Across the first 20 years of succession,
      the period for which we have accurate SF age data, biomass recovered at 1.2% per
      year, equivalent to a carbon uptake rate of 2.25 Mg/ha per year, while, on
      average, species richness and composition recovered at 2.6% and 2.3% per year,
      respectively. For all taxonomic groups, biomass was strongly associated with SF
      species distributions. However, other variables describing habitat complexity
      canopy cover and understory stem density-were equally important occurrence
      predictors for most taxa. Species responses to biomass revealed a successional
      transition at approximately 75 Mg/ha, marking the influx of high-conservation
      value forest species. Overall, our results show that naturally regenerating SFs
      can accumulate substantial amounts of carbon and support many forest species.
      However, given that the surveyed SFs failed to return to a typical UPF state, SFs
      are not substitutes for UPFs.

PMID- 30216602
TI  - Validity of the Manchester Triage System in emergency patients receiving life
      saving intervention or acute medical treatment-A prospective observational study
      in the emergency department.
AB  - RATIONALE, AIMS, AND OBJECTIVES: The spectrum of cases seen by emergency
      departments ranges from minor illnesses or injuries to complex diseases with high
      mortality. Some patients require life-saving interventions (LSIs) or therapeutic
      treatment for an acute illness to prevent an expected imminent life-threatening
      condition immediately upon arrival. No published study has evaluated the validity
      of the Manchester Triage System (MTS) in the context of immediate LSI or acute
      emergency treatment (AET). METHODS: The definition of LSI was based on a
      literature search. AET was defined by an expert panel based on current emergency
      guidelines and diagnostic guideline recommendations. In a 4-month observation
      period, an independent external observer documented all executed LSIs or AETs
      using a checklist. Sensitivity, negative predictive value, likelihood ratio
      negative (LR-), and accuracy of MTS triage level for the identification of
      patients receiving an LSI or AET were calculated. RESULTS: In 1762 patients, 40
      (2.3%) LSIs and 89 (5.1%) AETs were observed. In the LSI group, sensitivity of
      MTS was 75.0%, negative predictive value (NPV) was 99.2% (95% CI: 98.7%-99.6%),
      LR- was 0.303 (95% CI: 0.189-0.487) and accuracy (ACC) was 98.5% (95% CI: 97.8%
      98.9%). In the AET group, sensitivity was 82.0%, NPV was 98.9% (95% CI: 98.1%
      99.3%), LR- was 0.206 (95% CI: 0.132-0.322), and ACC was 86.5% (95% CI: 84.9%
      88.1%). CONCLUSION: The MTS is a valid instrument for a first assessment of
      emergency patients in critical condition upon arrival.

PMID- 30216603
TI  - Infantile bullous pemphigoid successfully treated with combined pulse
      corticosteroids and high-dose IVIG.
AB  - Bullous pemphigoid is the most common autoimmune blistering disorder in the
      elderly. It affects people aged 70 years or older. Clinically it is characterized
      by intensely pruritic eruption consisting of widespread tense blisters on an
      erythematous background. It is associated with cellular and humoral responses
      against hemidesmosomal components of the skin and mucous membranes. In contrast,
      infantile bullous pemphigoid is exceedingly rare disease and presents with some
      unique features like favorable prognosis, possible association with vaccination,
      and primary involvement of acral surfaces. Herein, we present a case of 4,5-month
      old infant with neonatal pemphigoid, successfully treated with a combination of
      intravenous immunoglobulins and pulse methylprednisolone.

PMID- 30216604
TI  - Bacterial Cell-Surface Display of Semisynthetic Cyclic Peptides.
AB  - Semisynthetic cyclic peptides containing both non-proteinogenic building blocks,
      as the synthetic part, and a genetically encoded sequence amenable to DNA-based
      randomization hold great potential to expand the chemical space in the quest for
      novel bioactive peptides. Key to an efficient selection of novel binders to
      biomacromolecules is a robust method to link their genotype and phenotype. A
      novel bacterial cell surface display technology has been developed to present
      cyclic peptides composed of synthetic and genetically encoded fragments in their
      backbones. The fragments were combined by protein trans-splicing and
      intramolecular oxime ligation. To this end, a split intein half and an unnatural
      amino acid were displayed with the genetically encoded part on the surface of
      Escherichia coli. Addition of the synthetic fragment equipped with the split
      intein partner and an aminooxy moiety, as well as the application of a pH-shift
      protocol, resulted in the onsurface formation of the semisynthetic cyclic
      peptide. This approach will serve for the generation of cyclic peptide libraries
      suitable for selection by fluorescence-activated cell sorting, and more generally
      enables chemical modification of proteins on the bacterial surface.

PMID- 30216605
TI  - A hexagonal Fourier model of grid cells.
AB  - Grid cells in rat medial entorhinal cortex are widely thought to play a major
      role in spatial behavior. However, the exact computational role of the population
      of grid cells is not known. Here we provide a descriptive model, which
      nonetheless considers biologically feasible mechanisms, whereby the grid cells
      are viewed as a two-dimensional Fourier basis set, in hexagonal coordinates, with
      restricted availability of basis functions. With known properties imposed in the
      model parameters, we demonstrate how various empirical benchmark findings are
      straight-forward to understand in this model. We also explain how complex
      computations, inherent in a Fourier model, are feasible in the medial entorhinal
      cortex with simple mechanisms. We further suggest, based on model experiments,
      that grid cells may support a form of lossy compression of contextual
      information, enabling its representation in an efficient manner. In sum, this
      hexagonal Fourier model suggests how the entire population of grid cells may be
      modeled in a principled way, incorporates biologically feasible mechanisms and
      provides a potentially powerful interpretation of the relationship between grid
      cell activity and contextual information beyond spatial knowledge. This enables
      various phenomena to be modeled with relatively simple mechanisms, and leads to
      novel and testable predictions.

PMID- 30216606
TI  - The association between fecal hemoglobin concentration and oral potentially
      malignant disorders.
AB  - OBJECTIVES: The present study was to investigate the association between fecal
      hemoglobin (f-Hb) concentration and oral cancer and its precursor, oral
      potentially malignant disorders (OPMD). METHODS: We used a population-based
      longitudinal cohort study data based on both Taiwanese nationwide oral and
      colorectal cancer screening programs implemented between 2004 and 2009. The total
      of 235,234 smokers and/or betel-quid chewers aged 50 to 69 years free of oral
      cancer and OPMD at entry were followed up over time to quantify the association
      between baseline f-Hb concentration on newly diagnosed oral cancer and OPMD.
      RESULTS: The risk of OPMD increased with baseline f-Hb in a dose manner, yielding
      a statistically significant elevated risk of developing OPMD in parallel with the
      incremental concentration of f-Hb (adjusted hazard ratios = 0.99, 1,11, 1,07,
      1,57, and 1,63 for f-Hb categories of 1-9, 10-19, 20-49, 50-89, and >=90 ug Hb/g,
      respectively, as compared with the reference group (low and undetectable f-Hb
      concentrations)) However, there was lacking of a statistical significance for the
      corresponding association regarding the risk of oral cancer, which is possibly
      due to sparse cases given a shorter follow-up time. CONCLUSION: We discovered
      that f-Hb concentration was positively related to the risk of OPMD. f-Hb can be
      used as a biomarker for early detection of OPMD.

PMID- 30216607
TI  - Processes and challenges in clinical decision-making for children with speech
      sound disorders.
AB  - BACKGROUND: Children with speech-sound disorders (SSD) constitute a significant
      proportion of speech-language pathologists' (SLPs) caseloads. Previous research
      has investigated the clinical practice of SLPs intervening with children with
      SSD; however, little is known about the clinical decision-making underpinning
      their practice. AIMS: The clinical decision-making of SLPs working with children
      with SSD was explored to understand how their clinical decisions were influenced
      by: (1) beliefs about what works in therapy; (2) prior clinical experience; and
      (3) client and service-related variables. METHODS & PROCEDURES: Semi-structured,
      individual, in-depth interviews were conducted with 11 SLPs. Inductive thematic
      analysis was used to identify and explore key ideas and themes. OUTCOMES &
      RESULTS: Four themes emerged: (1) clinical decision-making procedures were highly
      individualized; (2) parental involvement was viewed as central to the success and
      progression of therapy; (3) therapy procedures were influenced by practice
      setting constraints; and (4) engaging in evidence-based practice within clinical
      settings was perceived as challenging. CONCLUSIONS & IMPLICATIONS: In clinical
      settings, a range of factors influence decision-making and therapy provided by
      SLPs to children with SSD. These SLPs had a high regard for clients' values and
      preferences. Prior clinical experiences also shaped clinical practice. Clinical
      decision-making was influenced by practice-setting constraints. SLPs are under
      pressure in their workplaces and are struggling to manage the competing demands
      on their time. Large clinical caseloads, heavy workloads, current service
      delivery models and changing family structures are all impacting on the provision
      of therapy to children with SSD and therapy outcomes. As a profession, there is a
      need to consider these barriers and identify ways to overcome them in order to
      assist SLPs to routinely adopt the highest standards of clinical practice for
      children with SSD.

PMID- 30216608
TI  - Pharmacophore Nanoarrays on DNA Origami Substrates as a Single-Molecule Assay for
      Fragment-Based Drug Discovery.
AB  - The rational combination of techniques from the fields of nanotechnology, single
      molecule detection, and lead discovery could provide elegant solutions to enhance
      the throughput of drug screening. We have synthesized nanoarrays of small
      pharmacophores on DNA origami substrates that are displayed either as individual
      ligands or as fragment pairs and thereby reduced the feature size by several
      orders of magnitude, as compared with standard microarray techniques. Atomic
      force microscopy-based single-molecule detection allowed us to distinguish potent
      protein-ligand interactions from weak binders. Several independent binding
      events, that is, strong, weak, symmetric bidentate, and asymmetric bidentate
      binding are directly visualized and evaluated. We apply this method to the
      discovery of bidentate trypsin binders based on benzamidine paired with aromatic
      fragments. Pairing of benzamidine with the dye TAMRA results in tenfold
      enhancement of the trypsin binding yield.

PMID- 30216609
TI  - Evaluation of Genotoxic and Cytotoxic effects of ethyl acetate extract of
      Aspergillus flavus on Spodoptera litura.
AB  - AIM: Recent concerns about the possible adverse effects of agricultural chemicals
      on health and environment have generated a considerable interest in biological
      alternatives. The present study aimed to test the insecticidal potential of
      fungus Aspergillus flavus and revealed its genotoxic and cytotoxic effects using
      Spodoptera litura (Fabricius) as a model. METHODS AND RESULTS: The fungus was
      isolated from the surface of the dead insect and investigated for its
      insecticidal potential against S. litura by bioassay studies. Significant
      increase in mortality, prolonged development period and reduced adult emergence
      in S. litura was observed in larva fed on diet supplemented with fungal extract.
      In addition, fungus was also found to cause oxidative stress, DNA damage and cell
      death. Significantly higher percentages of necrotic cells and DNA damage were
      observed in larvae treated with fungal extract. Furthermore, DNA repair studies
      predicted the longevity of toxic effects induced by fungus. Phytochemical and
      Ultra-High performance liquid chromatography (UHPLC) studies revealed the
      presence of phenolic compounds in the extract and Liquid chromatography-mass
      spectrometry (LC-MS) indicated it to be a non-aflatoxin strain of A. flavus.
      Fungal extract was less toxic to mammalian cell lines as compared to cytotoxic
      drug Dox (Doxurobin) in the MTT assay. CONCLUSION: The study highlights the
      insecticidal potential of A. flavus by revealing its genotoxicity and
      cytotoxicity causing potential. This is the first report showing the genotoxic
      and cytotoxic effects of the fungus A. flavus on S. litura. This article is
      protected by copyright. All rights reserved.

PMID- 30216610
TI  - Study on site-specific expression of bone formation and resorption factors in
      human dental follicles.
AB  - We sought to investigate site-specific expression of bone-regulatory factors
      expressed by human dental follicles and to compare the stimulated expression of
      tumour necrosis factor (ligand) superfamily, member 11/tumour necrosis factor
      receptor superfamily, member 11b (RANKL/OPG) in human dental follicle cells
      (HDFCs) from different patients. Analysis of bone-regulatory markers in follicles
      from 12 different study participants was performed using RT-qPCR and
      immunofluorescence; apical and coronal segments from each dental follicle were
      processed independently. Four additional dental follicles were used for cell
      cultures; HDFCs were precultured in osteogenic medium to initiate differentiation
      and thereafter cultured with 10-6 M forskolin (FSK) to activate the protein
      kinase cAMP (PKA/cAMP) signalling pathway and induce RANKL/OPG expression. We
      demonstrate that RANKL expression is significantly higher in the coronal part of
      follicles than in the apical part. High levels of collagen type 1 (COL1),
      alkaline phosphatase (ALP) and Gap-junction protein, alpha 1, 43 kDa (CX43) were
      expressed, whereas expression of Sp7 transcription factor (OSX), bone
      morphogenetic protein 2 (BMP2), colony-stimulating factor 1 (CSF-1), chemokine (C
      C motif) ligand 2 (MCP1), and OPG was low in all samples. The immunofluorescence
      localization of CSF-1, MCP1, osteocalcin (OCN), RANKL, and BMP2 was not specific
      for either part of the follicles. In conclusion, a consistently high expression
      of CX43 suggests that gap-junction communication in HDFCs is essential for the
      eruption process. Furthermore, the induced expression of RANKL in HDFCs varies
      significantly between individuals and may relate to clinical variations in tooth
      eruption.

PMID- 30216612
TI  - Tandem Regioselective Hydroformylation-Hydrogenation of Internal Alkynes Using a
      Supramolecular Catalyst.
AB  - New supramolecular ligands containing an acyl guanidine function were designed
      based on the strategy of increasing the pi-acceptor ability of phosphine ligands
      by introducing electron-withdrawing groups. By applying this novel catalytic
      system, a general protocol for the Rh-catalysed hydroformylation-hydrogenation of
      unsymmetrical internal alkynes, functionalized with a carboxylic acid, was found
      to furnish aliphatic aldehydes in high regio- and chemoselectivities. Control
      experiments confirm the enzyme-like supramolecular catalyst mode of action.

PMID- 30216611
TI  - Faceted-Charge Patchy LnF3 Nanocrystals with a Selective Solvent Interaction.
AB  - A fast and single-step preparation of patchy LnF3 faceted-charge nanocrystals are
      described. These hexagonal faceted nanocrystals allow the spontaneous selective
      adsorption of cations or anions in the different faces, producing stable and well
      defined patches of different charge. The mechanism for the formation of the
      patches and the properties of the obtained nanocrystals were characterized by a
      combination of experimental techniques and all-atomic molecular dynamics
      simulations. The spontaneous dual-charged surface as well as the luminescence
      effects that can be achieved by doping host-LaF3 systems make these new
      nanocrystals interesting both from a fundamental point of view and for a wide
      range of applications.

PMID- 30216613
TI  - Complementary feeding: Attitudes, knowledge and practices of urban families in
      northern Thailand.
AB  - AIM: Urban families in middle-income countries are currently facing cultural and
      lifestyle transition. Changing from an agricultural to an industrial society may
      affect family roles and child-care practices. The present study aims to reveal
      family attitudes, knowledge and practices focusing on complementary feeding (CF).
      METHODS: A cross-sectional study was conducted in three Child Health Clinics in
      Chiang Mai, Thailand. Self-administered questionnaires were given to families
      caring for healthy infants and children less than 18 months of age during October
      to November 2016. RESULTS: One-hundred and eight respondents completed
      questionnaires. The study found different attitudes and knowledge gaps between
      the respondents who were mothers and other family members ('others'). The
      'others' were less likely to value CF as a crucial factor promoting child growth
      and development. Moreover, they had misperceptions about the benefits of animal
      based protein and were less confident in their ability to feed the child
      properly. Most families reported timely introduction of complementary food, using
      proper milk products and encouraging age-appropriate feeding methods. However,
      there were undesirable practices including delaying introduction of animal-based
      protein, inadequate food diversity, the use of seasoning, feeding premasticated
      food and offering food as a reward. CONCLUSIONS: These findings suggest that
      nutritional education should be extended to all caregivers involved in CF to
      improve the adherence to feeding recommendations.

PMID- 30216614
TI  - The distribution of mycotoxins in a heterogeneous wheat field in relation to
      microclimate, fungal and bacterial abundance.
AB  - AIM: To observe the variation in accumulation of Fusarium and Alternaria
      mycotoxins across a topographically heterogeneous field and tested biotic (fungal
      and bacterial abundance) and abiotic (microclimate) parameters as explanatory
      variables. METHODS AND RESULTS: We selected a wheat field characterized by a
      diversified topography, to be responsible for variations in productivity and in
      canopy-driven microclimate. Fusarium and Alternaria mycotoxins where quantified
      in wheat ears at three sampling dates between flowering and harvest at 40 points.
      Tenuazonic acid (TeA), alternariol (AOH), alternariol monomethyl ether (AME),
      tentoxin (TEN), deoxynivalenol (DON), zearalenone (ZEN) and deoxynivalenol-3
      Glucoside (DON.3G) were quantified. In canopy temperature, air and soil humidity
      were recorded for each point with data-loggers. Fusarium spp. as trichothecene
      producers, Alternaria spp. and fungal abundances were assessed using qPCR.
      Pseudomonas fluorescens bacteria were quantified with a culture based method. We
      only found DON, DON.3G, TeA and TEN to be ubiquitous across the whole field,
      while AME, AOH and ZEN were only occasionally detected. Fusarium was more
      abundant in spots with high soil humidity, while Alternaria in warmer and drier
      spots. Mycotoxins correlated differently to the observed explanatory variables:
      positive correlations between DON accumulation, tri 5 gene and Fusarium abundance
      were clearly detected. The correlations among the others observed variables, such
      as microclimatic conditions, varied among the sampling dates. The results of
      statistical model identification do not exclude that species coexistence could
      influence mycotoxin production. CONCLUSIONS: Fusarium and Alternaria mycotoxins
      accumulation varies heavily across the field and the sampling dates, providing
      the realism of landscape-scale studies. Mycotoxin concentrations appear to be
      partially explained by biotic and abiotic variables. SIGNIFICANCE AND IMPACT OF
      THE STUDY: We provide a useful experimental design and useful data for
      understanding the dynamics of mycotoxin biosynthesis in wheat.

PMID- 30216615
TI  - Clusters of the Ionic Liquid 1-Hydroxyethyl-3-methylimidazolium Picrate: From
      Theoretical Prediction in the Gas Phase to Experimental Evidence in the Solid
      State.
AB  - Interonic interactions determine the macroscopic properties of ionic liquids
      (ILs). Hence, unravelling the relationships between the microscopic and
      macroscopic scales is key for rational design. Combining density functional
      theory (DFT) calculations of isolated ion pairs and vibrational spectroscopy of
      the condensed phase (fluid or solid) has become a very common approach. In the
      present work, we make a step towards understanding how the physicochemical
      effects in small gas phase clusters of a hydroxyl functionalized imidazolium
      picrate IL relate with the molecular structure and interactions of the
      corresponding solid material taking 1-hydroxyethyl-3-methylimidazolium picrate,
      C2 OHmimPic, as an example. In the isolated ion pair, strong alkyl-OH???Pic
      hydrogen bonding interactions are found rather than the commonly observed
      hydrogen bonding interactions at the slightly acidic C(2)-H site of the
      imidazolium ring. However, this part of the cation plays an important role when
      clusters of ion pairs in the gas phase and inside a crystal lattice are
      considered. For example, in the dimeric ion-pair cluster, one centre (O*) with
      two interaction sites (C(2)-H-O* and alkyl OH-Pic) is observed. This
      configuration is suggested by single crystal X-ray diffraction (XRD), vibrational
      spectroscopy, and the dispersion-corrected DFT calculations. Hence, the study
      provides evidence for the appearance of theoretical gas phase clusters in an
      actual solidified ionic liquid. This ion pair dimer formation may be a general
      behavior of hydroxyl functionalized imidazolium ILs, but further research is
      needed to draw a final conclusion. Moreover, the Raman spectra confirm the
      exclusive gauche conformation of the hyroxyl functionalized alkyl chain.

PMID- 30216616
TI  - Disorder-specific attachment characteristics and experiences of childhood abuse
      and neglect in adolescents with anorexia nervosa and a major depressive episode.
AB  - For the first time, the present study investigates disorder-specific attachment
      characteristics and childhood trauma in adolescent inpatients with anorexia
      nervosa (n = 30, girls/boys: 28/2, age: M = 14.84, SD = 1.20), a major depressive
      episode (n = 30, girls/boys: 27/3, age: M = 15.14, SD = 1.50), and controls (n =
      60, girls/boys: 44/16, age: M = 16.10, SD = 1.20). We used the Structured
      Clinical Interview to diagnose Axis I disorders, the Adult Attachment Projective
      Picture System to classify attachment representations, and the Childhood Trauma
      Questionnaire to assess child maltreatment. Our findings demonstrate an
      overrepresentation of the unresolved attachment status in the patient samples. A
      one-way analysis of variance succeeded by Bonferroni post hoc tests indicated
      that adolescents with anorexia nervosa show more isolation and dissolution of
      boundaries between life and death when confronted with situations of solitude.
      Although they report moderate to severe levels of traumatic childhood
      experiences, they tend to minimize those. Adolescents with a major depressive
      episode report higher levels of emotional abuse and neglect in their childhood,
      leaving them in a state of failed protection and danger during attachment
      distress. Integrating these attachment-related characteristics into specific
      psychotherapeutic interventions might be associated with a better outcome in that
      age group.

PMID- 30216617
TI  - Suture techniques during laparoscopic and robot-assisted partial nephrectomy: a
      systematic review and quantitative synthesis of peri-operative outcomes.
AB  - OBJECTIVE: To summarize the available evidence on renorrhaphy techniques and to
      assess their impact on peri-operative outcomes after minimally invasive partial
      nephrectomy (MIPN). MATERIALS AND METHODS: A systematic review of the literature
      was performed in January 2018 without time restrictions, using MEDLINE, Cochrane
      and Web of Science databases according to the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses statement recommendations. Studies providing
      sufficient details on renorrhaphy techniques during laparoscopic or robot
      assisted partial nephrectomy and comparative studies focused on peri-operative
      outcomes were included in qualitative and quantitative analyses, respectively.
      RESULTS: Overall, 67 and 19 studies were included in the qualitative and
      quantitative analyses, respectively. The overall quality of evidence was low.
      Specific tumour features (i.e. size, hilar location, anatomical complexity,
      nearness to renal sinus and/or urinary collecting system), surgeon's experience,
      robot-assisted technology, as well as the aim of reducing warm ischaemia time and
      the amount of devascularized renal parenchyma preserved represented the key
      factors driving the evolution of the renorrhaphy techniques during MIPN over the
      past decade. Quantitative synthesis showed that running suture was associated
      with shorter operating and ischaemia time, and lower postoperative complication
      and transfusion rates than interrupted suture. Barbed suture had lower operating
      and ischaemia time and less blood loss than non-barbed suture. The single-layer
      suture technique was associated with shorter operating and ischaemia time than
      the double-layer technique. No comparisons were possible concerning renal
      functional outcomes because of non-homogeneous data reporting. CONCLUSIONS:
      Renorrhaphy techniques significantly evolved over the years, improving outcomes.
      Running suture, particularly using barbed wires, shortened the operating and
      ischaemia times. A further advantage could derive from avoiding a double-layer
      suture.

PMID- 30216618
TI  - Isolation from natural habitat reduces yield and quality of passion fruit.
AB  - Loss and fragmentation of native vegetation negatively affect crop pollinators
      and productivity of several crop species. The yellow passion fruit is an
      excellent model to investigate this issue, because its main pollinators are
      sensitive to deforestation. Seasonality also influences fruit set of crop species
      that are pollinated by bees. Climate determines plant flowering patterns and
      consequently affects pollinator activity. Little is known on effects of
      pollinators on crop quality in general, and particularly of many tropical fruits
      that have multiple fruiting seasons throughout the year, such as passion fruit.
      Our hypothesis is that the distance to the native vegetation and climate
      seasonality affect the pollination and fruit production of cultivated,
      hermaphrodite, self-incompatible, protandrous species that depend on large-sized
      bees to set fruit. We observed flowers of the yellow passion fruit in eight areas
      at different distances (600-4,000 m) from a dry seasonal forest (Caatinga). We
      compared the frequency of the main floral visitor (pollinators and robbers)
      visits and fruit set among areas at the beginning and end of the dry and rainy
      seasons. Xylocopa species were pollinators, and Apis mellifera, Trigona spinipes
      and a hummingbird were robbers. Xylocopa visits diminished with increasing
      distance to native remnants, converse to what was observed for the robbers at the
      beginning of the dry season. Fruit set was higher at the beginning of the dry
      season. The distance to the forest affected quality of fruits in terms of length,
      diameter and skin thickness, which all decreased with increase in remnant
      distance. Our results show that insect pollination is higher in the dry season,
      increasing profitability and reducing labour costs for the producer. Considering
      the influence of distance to native vegetation on pollination, robbery and fruit
      quality, our study reinforces the necessity for conservation of native vegetation
      remnants.

PMID- 30216619
TI  - Dynamic Migration of Surface Fluorine Anions on Cobalt-Based Materials to Achieve
      Enhanced Oxygen Evolution Catalysis.
AB  - Fluorine-anion surface engineering has now been used to activate catalytic active
      species, representing a completely new way of reconstruction toward oxygen
      evolution reaction (OER) active species. The electronegativity of the fluorine
      anion is the strongest so that it will be much easier to form weak metal-fluorine
      bonds with stronger ionicity, contributing to the dynamic migration of fluorine
      anions and finally enriching on the surface of both cobalt-based
      oxide/oxyhydroxide. Surface enrichment of fluorine anions endows more hydrophilic
      surface character for accelerating the key process of oxygen-related intermediate
      adsorption. Combining with an obviously improved electron transfer capacity, the
      F-CoOOH/NF catalyst exhibits a greatly enhanced OER activity (270 mV at 10 mA cm
      2 ) and reaction kinetics (54 mV dec-1 ) in alkaline medium. Surface anion
      engineering introduces a new concept for rational design advanced OER catalysts
      for energy conversion system.

PMID- 30216620
TI  - Chemotactic Micro- and Nanodevices.
AB  - Preparation of autonomous chemotactic micro- and nanomachines represents one of
      the most difficult challenges of modern materials science. To construct a device
      mimicking the behavior of many microorganisms, which evolved their chemotactic
      abilities during the millennia of evolution, places extreme demands on the
      imagination and abilities of researchers. However, with the chemotactic devices
      in hand, many novel and interesting applications of micromachines could be
      implemented. The introduction of an autonomous navigation, independent of the
      external control with electric, magnetic, or electromagnetic field is crucial for
      applications in environmental remediation and might be advantageous in medical
      applications. This Minireview summarizes the development in the field of
      chemotactic micro- and nanomachines, describes the trends in their construction,
      and compares the different approaches to their construction considering the areas
      of possible application of the devices.

PMID- 30216621
TI  - The reverse smile trick: how to transform a double-stapled anastomosis into a
      single-stapled anastomosis - a video vignette.

PMID- 30216622
TI  - Long-term testosterone therapy in type 2 diabetes is associated with reduced
      mortality without improvement in conventional cardiovascular risk factors.
AB  - OBJECTIVES: To further characterize the beneficial impact of testosterone
      replacement therapy (TRT) on the association between mortality and hypogonadism
      (HG) in men with type 2 diabetes (T2DM), by determining, firstly, if changes in
      cardiovascular disease (CVD) risk factors after TRT play a role, secondly,
      whether the reduction in mortality is lost when TRT is discontinued and, finally,
      the presence of subgroups where benefit may be greater. MATERIALS AND METHODS: We
      studied 857 men with T2DM, screened for the BLAST randomized controlled trial,
      over 3.8 years of follow-up. The men were stratified first by testosterone
      levels: group 1: total testosterone (TT) >12 nmol/L and free testosterone (FT)
      >0.25 nmol/L; Group 2: TT <=12 nmol/L or FT <=0.25 nmol/L. Group 2 was further
      stratified into those not on TRT (Group 2a) and those on TRT (Group 2b). Group 2b
      was further stratified by whether TRT was discontinued (Group 2b1) or not (Group
      2b2). The principal outcome, mortality, was studied using Cox regression.
      RESULTS: We found that TRT was not associated with improvements in CVD risk
      factors. CVD risk factors (baseline and changes during follow-up) were not
      associated with mortality. Men in Group 1 and Group 2b were found to have lower
      mortality (reference: Group 2a), even with CVD risk factors included in the
      regression models. Mortality was lower in men in Group 2b1 (6.2%) and Group 2b2
      (0%) compared with those in Group 2a (16.9%). The lower mortality associated with
      Group 1 and Group 2b was observed primarily in older (>64.6 years) and less
      overweight (<=93.8 kg) men. CONCLUSIONS: The benefits associated with normal
      testosterone levels and TRT (even after discontinuation) do not appear to be
      related to improvements in the CVD risk factors studied. In view of TRT having
      greater impact in men of lower weight, better outcomes may be achieved with
      concurrent TRT and weight reduction programmes.

PMID- 30216623
TI  - Relationship between oxidative stress and lower urinary tract symptoms: results
      from a community health survey in Japan.
AB  - OBJECTIVE: To investigate the relationship between oxidative stress and lower
      urinary tract symptoms (LUTS) in a community-dwelling population. MATERIALS AND
      METHODS: The cross-sectional study included 1 113 people who participated in the
      Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed
      using structured questionnaires, including the International Prostate Symptom
      Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS >
      5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to
      severe symptoms. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and advanced glycation end
      products (AGEs) were measured by urine analysis and skin autofluorescence,
      respectively. The relationship between oxidative stress and LUTS was investigated
      using logistic regression analyses. RESULTS: This study included 431 men and 682
      women. AGEs and 8-OHdG levels were significantly higher in severe forms of LUTS.
      Multivariate logistic regression analyses showed that AGE levels were
      significantly associated with a higher frequency of nocturia but were not
      associated with IPSS, OABSS or urge incontinence. No significant association was
      observed between LUTS and 8-OHdG levels. CONCLUSIONS: We observed a significant
      association between AGE levels and nocturia score > 1. Further research is
      necessary to clarify a possible causal relationship between oxidative stress and
      nocturia.

PMID- 30216624
TI  - Impact of 5alpha-reductase inhibitor and alpha-blocker therapy for benign
      prostatic hyperplasia on prostate cancer incidence and mortality.
AB  - OBJECTIVE: To investigate the use of 5alpha-reductase inhibitors (5ARIs) and
      alpha-blockers among men with benign prostatic hyperplasia (BPH) in relation to
      prostate cancer (PCa) incidence, severity and mortality. PATIENTS AND METHODS: A
      retrospective 20-year cohort study in men residing in Saskatchewan, aged 40-89
      years, with a BPH-coded medical claim between 1995 and 2014, was conducted. Cox
      proportional hazards regression was used to compare incidence of PCa diagnosis,
      metastatic PCa, Gleason score 8-10 PCa, and PCa mortality among 5ARI users (n = 4
      571), alpha-blocker users (n = 7 764) and non-users (n = 11 677). RESULTS: In
      comparison with both non-users and alpha-blocker users, 5ARI users had a ~40%
      lower risk of a PCa diagnosis (11.0% and 11.4% vs 5.8%, respectively), and alpha
      blocker users had an 11% lower risk of a PCa diagnosis compared with non-users.
      Overall, the incidence of metastatic PCa and PCa mortality was not significantly
      different among 5ARI or alpha-blocker users compared with non-users (adjusted
      hazard ratios [HR] of metastatic PCa: 1.12 and 1.13, respectively, and PCa
      mortality: 1.11 and 1.18, respectively, P > 0.05 for both drugs), but both 5ARI
      and a-blocker users had ~30% higher risk of Gleason score 8-10 cancer, adjusted
      HR 1.37, 95% confidence interval [CI] 1.03-1.82, P = 0.03, and adjusted HR 1.28,
      95% CI 1.03-1.59, P = 0.02, respectively compared with non-users. CONCLUSION: The
      use of 5ARIs was associated with lower risk of PCa diagnosis, regardless of
      comparison group. Risk of high grade PCa was higher among both 5ARI users and
      alpha-blocker users compared with non-users; however, this did not translate into
      higher risk of PCa mortality.

PMID- 30216625
TI  - Rectal neuroendocrine tumours treated using endoscopic submucosal dissection with
      myectomy - a video vignette.

PMID- 30216626
TI  - Proximity Ligation-Based Fluorogenic Imaging Agents for Neuraminidases.
AB  - Reagents to visualize and localize neuraminidase activity would be valuable
      probes to study the role of neuraminidases in normal cellular processes as well
      as during viral infections or cancer development. Herein, a new class of
      neuraminidase-imaging probes that function as proximity ligation reagents by
      releasing a highly reactive fluorophore that tags nearby cellular material is
      described. It is further demonstrated that it is possible to create an influenza
      virus-specific reagent, which can specifically detect influenza virus infections
      in mammalian cells. These reagents have potential use as specific histological
      probes independent of viral antigenicity and, therefore, offer some advantages
      over commonly used anti-neuraminidase antibodies.

PMID- 30216627
TI  - Comparison of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus
      anticholinergic agents in the management of paediatric monosymptomatic nocturnal
      enuresis: a network meta-analysis.
AB  - OBJECTIVE: To assess the efficacy of desmopressin, alarm, desmopressin plus
      alarm, and desmopressin plus anticholinergic agent (AA) therapy in the management
      of paediatric monosymptomatic nocturnal enuresis (MNE) using a network meta
      analysis. MATERIAL AND METHODS: We searched the electronic databases PubMed,
      Cochrane Library, EMBASE and Web of Science from inception to 1 March 2018.
      Randomized controlled trials (RCTs) that compared desmopressin, alarm,
      desmopressin plus alarm, and desmopressin plus AAs were identified. The network
      meta-analysis was conducted with software R 3.3.2 and STATA 14.0. RESULTS:
      Eighteen RCTs with a total of 1 649 participants were included. The meta-analysis
      results showed that complete response (CR) and success rates with desmopressin
      plus AAs were higher than with desmopressin or alarm monotherapy. Success rates
      for desmopressin plus alarm therapy were higher than for alarm monotherapy. No
      obvious difference was observed between desmopressin plus AAs and desmopressin
      plus alarm therapy with regard to CR rate and success rate. The relapse rate with
      alarm monotherapy was much lower than with desmopressin monotherapy. Adverse
      events seemed to be infrequently and tolerable for all treatments. The ranking
      probability results were as follows: desmopressin plus AA ranked first for the
      outcomes of CR and success, desmopressin plus alarm therapy ranked first for mean
      number of wet nights per week, and alarm therapy had the lowest relapse rate.
      CONCLUSIONS: The network meta-analysis showed that desmopressin had similar
      efficacy to alarm therapy but a higher relapse rate. Desmopressin plus AA therapy
      was associated with better efficacy than and a similar relapse rate to
      desmopressin monotherapy. Desmopressin plus alarm therapy was similar to both
      desmopressin and alarm monotherapy in efficacy. All treatments, including
      desmopressin plus AAwere associated with tolerable adverse events; however,
      additional high-quality studies are needed for further evaluation of these
      treatments.

PMID- 30216628
TI  - Perspective: regulation of pest and disease control strategies and why (many)
      economists are concerned.
AB  - Pests and diseases are a continuous challenge in agriculture production. A wide
      range of control strategies have been and will continue to be developed. New
      control strategies are in almost all countries around the world assessed prior to
      approval for use in farmers' fields. This is rightly so to avoid and even reduce
      negative effects for human health and the environment. Over the past decades the
      approval processes have become increasingly politicized resulting in an increase
      in the direct approval costs and the length in approval time without increasing
      the safety of the final product. This reduces the development of control
      strategies and often has negative human health and environmental effects.
      Possibilities exist for improvements. They include reducing approval costs and
      approval time by streamlining the approval process and substituting approval
      requirements by strengthening ex-post liability. (c) 2018 Society of Chemical
      Industry.

PMID- 30216629
TI  - Occupation and risk of cancer of the renal pelvis in Nordic countries.
AB  - OBJECTIVES: To evaluate occupational variation in the incidence of the malignant
      neoplasm of the renal pelvis in the population of the Nordic countries: Denmark,
      Iceland, Finland, Norway and Sweden. MATERIALS AND METHODS: The study cohort
      comprised 14.9 million individuals. Data on occupational history were obtained
      from national censuses. Standardized incidence ratios (SIRs) were calculated for
      each occupation. RESULTS: The highest SIRs were found in seamen (1.51, 95%
      confidence interval [CI] 1.23-1.82), printers (1.39, 95% CI 1.11-1.71), welders
      (1.37, 95% CI 1.03-1.78), and public safety workers (1.35, 95% CI 1.12-1.62). The
      lowest SIRs were observed in forestry workers (0.47, 95% CI 0.35-0.62), gardeners
      (0.72, 95% CI 0.62-0.83) and woodworkers (0.81, 95% CI 0.72-0.91). CONCLUSIONS:
      The study suggests that there is an association between profession and risk of
      malignancy of the renal pelvis. The possible associations between exposure to
      asbestos, heavy metals and welding fumes, and risk of developing the disease
      should be studied further.

PMID- 30216630
TI  - Simultaneous laparoscopic totally extraperitoneal and transabdominal
      preperitoneal repair for bilateral inguinal hernia in a patient with a history of
      robotic prostatectomy - a video vignette.

PMID- 30216631
TI  - Interface interactions between betagamma-crystallin domain and Ig-like domain
      render Ca2+ -binding site inoperative in abundant perithecial protein of
      Neurospora crassa.
AB  - We describe a set of proteins in which a betagamma-crystallin domain pairs with
      an Ig-like domain, and which are confined to microbes, like bacteria, slime molds
      and fungi. DdCAD-1 (Ca2+ -dependent cell adhesion molecule-1) and abundant
      perithecial protein (APP) represent this class of molecules. Using the crystal
      structure of APP-NTD (N-terminal domain of APP), we describe its mode of Ca2+
      binding and provide a generalized theme for correct identification of the Ca2+ 
      binding site within this class of molecules. As a common feature, one of the two
      Ca2+ -binding sites is non-functional in the betagamma-crystallin domains of
      these proteins. While APP-NTD binds Ca2+ with a micromolar affinity which is
      comparable to DdCAD-1, APP surprisingly does not bind Ca2+ . Crystal structures
      of APP and Ca2+ -bound APP-NTD reveal that the interface interactions in APP
      render its Ca2+ -binding site inoperative. Thus, heterodomain association
      provides a novel mode of Ca2+ -binding regulation in APP. Breaking the interface
      interactions (mutating Asp30Ala, Leu132Ala and Ile135Ala) or separation from the
      Ig-like domain removes the constraints upon the required conformational
      transition and enables the betagamma-crystallin domain to bind Ca2+ . In
      mechanistic detail, our work demonstrates an interdomain interface adapted to
      distinct functional niches in APP and its homolog DdCAD-1.

PMID- 30216633
TI  - Vascular compliance in women with polycystic ovary syndrome treated with
      spironolactone.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women
      of reproductive age in the United States and has been associated with several
      diseases including cardiovascular disease, obesity, and glucose intolerance. In
      this study, systolic blood pressure, diastolic blood pressure, pulse pressure
      (vascular compliance), large artery elasticity, systemic vascular resistance
      (SVR), total vascular impedance (TVI), and body mass index (BMI) were measured
      before and after treatment with spironolactone in 10 women with PCOS. Systolic
      BP, diastolic BP, and BMI were similar prior to treatment and after treatment.
      Pulse pressure decreased slightly post-treatment compared to pretreatment but not
      to significance (P = 0.07). The results show that after treatment with
      spironolactone, there was a statistically significant increase in large artery
      elasticity (P = 0.047), while there was a statistically significant decrease in
      SVR and TVI (P = 0.0005 and P = 0.03). This study indicates that treatment with
      spironolactone improves large artery elasticity and reduces systemic vascular
      resistance without any change in small artery elasticity.

PMID- 30216632
TI  - The nuclear receptor RXRA controls cellular senescence by regulating calcium
      signaling.
AB  - Calcium signaling is emerging as a key pathway controlling cellular senescence, a
      stable cell proliferation arrest playing a fundamental role in pathophysiological
      conditions, such as embryonic development, wound healing, cancer, and aging.
      However, how calcium signaling is regulated is still only partially understood.
      The inositol 1, 4, 5-trisphosphate receptor type 2 (ITPR2), an endoplasmic
      reticulum calcium release channel, was recently shown to critically contribute to
      the implementation of senescence, but how ITPR2 expression is controlled is
      unclear. To gain insights into the regulation of ITPR2 expression, we performed
      an siRNA screen targeting 160 transcription factors and epigenetic regulators.
      Interestingly, we discovered that the retinoid X receptor alpha (RXRA), which
      belongs to the nuclear receptor family, represses ITPR2 expression and regulates
      calcium signaling though ITPR2 and the mitochondrial calcium uniporter (MCU).
      Knockdown of RXRA induces the production of reactive oxygen species (ROS) and DNA
      damage via the ITPR2-MCU calcium signaling axis and consequently triggers
      cellular senescence by activating p53, whereas RXRA overexpression decreases DNA
      damage accumulation and then delays replicative senescence. Altogether, our work
      sheds light on a novel mechanism controlling calcium signaling and cellular
      senescence and provides new insights into the role of nuclear receptors.

PMID- 30216634
TI  - Thrombospondin 1 and cathepsin D improve prostate cancer diagnosis by avoiding
      potentially unnecessary prostate biopsies.
AB  - OBJECTIVES: To investigate and further validate if two novel cancer-related
      glycoproteins, discovered by a genetic-guided proteomics approach, can
      distinguish benign disease from prostate cancer (PCa) in men with enlarged
      prostates. PATIENTS AND METHODS: A retrospective study was performed that
      included men with a total prostate-specific antigen (PSA) concentration of 2.0-10
      ng/mL, negative digital rectal examination and enlarged prostate (volume >=35
      mL). Serum samples were collected between 2011 and 2016 at a single centre from
      474 men before they underwent prostate biopsy. Serum concentrations of
      thrombospondin 1 (THBS1) and cathepsin D (CTSD) glycoproteins were combined with
      the percentage of free PSA to total PSA ratio (%fPSA) to predict any or
      significant cancer at biopsy. RESULTS: The multivariable logistic regression
      model including THBS1, CTSD and %fPSA discriminated among biopsy-positive and
      biopsy-negative patients in the validation set with an area under the curve (AUC)
      of 0.86 (P < 0.001, 95% confidence interval (CI) 0.82-0.91), while %fPSA alone
      showed an AUC of 0.64 (P < 0.001, 95% CI 0.57-0.71). At 90% sensitivity for PCa,
      the specificity of the model was 62%, while %fPSA had a specificity of 23%. For
      high grade (Gleason score >= 7 in prostatectomy specimen) PCa, the specificity
      was 48% at 90% sensitivity, with an AUC of 0.83, (P < 0.001, 95% CI 0.77 to
      0.88). Limitations of the study include the retrospective set-up and single
      centre cohort. CONCLUSIONS: A model combining two cancer-related glycoproteins
      (THBS1 and CTSD) and %fPSA can improve PCa diagnosis and may reduce the number of
      unnecessary prostate biopsies because of its improved specificity for PCa when
      compared to %fPSA alone.

PMID- 30216635
TI  - Improving the effectiveness of lifestyle interventions for gestational diabetes
      prevention: a meta-analysis and meta-regression.
AB  - BACKGROUND: Diet and exercise during pregnancy have been used to prevent
      gestational diabetes mellitus (GDM) with some success. OBJECTIVE: To examine the
      effectiveness of lifestyle intervention on GDM prevention and to identify key
      effectiveness moderators to improve the prevention strategy. SEARCH STRATEGY:
      Pubmed, Scopus, Cochrane, and cross-references were searched. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) evaluating lifestyle interventions during
      pregnancy for GDM prevention. DATA COLLECTION AND ANALYSIS: Two independent
      reviewers extracted data. A random-effects model was used to analyse the relative
      risk (RR) and 95% confidence interval (95% CI). Meta-regressions and subgroup
      analyses were used to investigate important moderators of effectiveness. MAIN
      RESULTS: Forty-seven RCTs involving 15 745 participants showed that diet and
      exercise during pregnancy were preventive of GDM (RR 0.77, 95% CI 0.69-0.87).
      Four key aspects were identified to improve the preventive effect: targeting the
      high-risk population; an early initiation of the intervention; the correct
      intensity and frequency of exercise; and gestational weight gain management.
      Although 24 RCTs targeted women who were overweight or obese, body mass index
      (BMI) failed to predict the effectiveness of an intervention. Instead,
      interventions are most effective in high-incidence populations rather than simply
      in women who are overweight or obese. Furthermore, exercise of moderate intensity
      for 50-60 minutes twice a week could lead to an approximately 24% reduction in
      GDM. CONCLUSION: The best strategy to prevent GDM is to target the high-risk
      population predicted by risk evaluation models and to control the gestational
      weight gain of women through intensified diet and exercise modifications early in
      their pregnancy. TWEETABLE ABSTRACT: Four key effectiveness moderators of
      lifestyle interventions for GDM prevention.

PMID- 30216636
TI  - Laparoscopic repair of a massive Morgagni hernia - a video vignette.

PMID- 30216638
TI  - From thrombasthenia to next generation thrombocytopenia: Neonatal alloimmune
      thrombocytopenia induced by maternal Glanzmann thrombasthenia.
AB  - BACKGROUND: Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder
      of platelet function caused by mutations in the genes coding for integrin
      alphaIIbbeta3. The aim of this study was to examine the outcome of newborns of GT
      mothers, with emphasis on thrombocytopenia and bleeding manifestations and their
      relation to maternal antiplatelet antibodies. PROCEDURE: Medical files of all
      female patients with GT treated in a single tertiary center from 1999 to 2017
      were searched for details on pregnancy and birth. The medical files of their
      newborns were retrieved, and data on the postnatal course were collected.
      RESULTS: Nine babies were born to five patients with GT at our center during the
      study period. Three of the nine newborns had severe thrombocytopenia, and all
      three were offspring of GT mothers who were positive for antiplatelet antibodies.
      CONCLUSION: Pregnant GT patients should be examined for platelet antibodies.
      Assessment and management protocols (including treatment with intravenous
      immunoglobulins) for fetal and neonatal alloimmune thrombocytopenia should be
      considered.

PMID- 30216637
TI  - Targeting the phospholipase A2 receptor ameliorates premature aging phenotypes.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a lethal premature aging that
      recapitulates many normal aging characteristics. This disorder is caused by
      mutation in the LMNA gene leading to the production of progerin which induces
      misshapen nuclei, cellular senescence, and aging. We previously showed that the
      phospholipase A2 receptor (PLA2R1) promotes senescence induced by replicative,
      oxidative, and oncogenic stress but its role during progerin-induced senescence
      and in progeria is currently unknown. Here, we show that knockdown of PLA2R1
      prevented senescence induced by progerin expression in human fibroblasts and
      markedly delayed senescence of HGPS patient-derived fibroblasts. Whole-body
      knockout of Pla2r1 in a mouse model of progeria decreased some premature aging
      phenotypes, such as rib fracture and decreased bone content, together with
      decreased senescence marker. Progerin-expressing human fibroblasts exhibited a
      high frequency of misshapen nuclei and increased farnesyl diphosphate synthase
      (FDPS) expression compared to controls; knockdown of PLA2R1 reduced the frequency
      of misshapen nuclei and normalized FDPS expression. Pamidronate, a FDPS
      inhibitor, also reduced senescence and misshapen nuclei. Downstream of PLA2R1, we
      found that p53 mediated the progerin-induced increase in FDPS expression and in
      misshapen nuclei. These results suggest that PLA2R1 mediates key premature aging
      phenotypes through a p53/FDPS pathway and might be a new therapeutic target.

PMID- 30216640
TI  - Enantioselective Carbonyl Catalysis Enabled by Chiral Aldehydes.
AB  - Organocatalytic methods have achieved spectacular advancements for the
      preparation of chiral molecules in highly enantioenriched forms. The fast
      development of this field can mainly be attributed to the evolution of general
      and reliable activation modes. The discovery and identification of new activation
      modes are therefore highly desirable to push the boundaries of asymmetric
      reactions. In this Minireview, recent advances in enantioselective carbonyl
      catalysis, one useful subbranch of organocatalysis for the efficient activation
      of simple amines, will be summarized. With elegantly designed chiral aldehyde
      catalysts, highly enantioselective and efficient asymmetric reactions can be
      developed. Continued development of enantioselective carbonyl catalysis is
      expected in the future.

PMID- 30216641
TI  - Morbid obesity and hypertension: The role of perirenal fat.
AB  - Accumulation of fat in renal sinus and hilum is associated with hypertension
      development. We evaluated the relationship between perirenal fat and hypertension
      in a population of morbidly obese patients and the potential variations after
      sleeve-gastrectomy. Two hundred and eighty-four morbidly obese patients were
      included in the study, and 126 underwent sleeve-gastrectomy. At baseline and 10
      12 months after surgery, we evaluated anthropometric parameters, blood pressure,
      glycometabolic, and lipidic assessment, and performed an ultrasonographic
      evaluation of visceral fat area and perirenal fat thickness. The perirenal fat
      thickness in hypertensive obese was higher than in nonhypertensive (13.6 +/- 4.8
      vs 11.6 +/- 4.1, P = 0.001). It showed a significant direct correlation with age,
      waist circumference, BMI, systolic blood pressure (SBP), insulinemia, HOMA-IR,
      glycated hemoglobin, and creatinine. The independent predictors (R2  = 0.129) of
      SBP were perirenal fat thickness (beta = 0.160, P = 0.022) and age (beta = 0.175,
      P = 0.011). After surgery, perirenal fat thickness significantly decreased (from
      13 +/- 4 to 9 +/- 4 mm, P <0.001). In the 89 hypertensive obese patients who
      underwent sleeve-gastrectomy, we observed a significant decrease in
      antihypertensive medications needed. Sixteen patients suspended therapy. The
      perirenal fat thickness in obese patients could be a valuable tool to define the
      risk of developing hypertension, providing the clinician with an additional
      parameter to define those who need a more aggressive treatment and could benefit
      most from bariatric surgery.

PMID- 30216642
TI  - Sexuality and cancer: The experience of adolescents and young adults.
AB  - There are many components affecting the experience of sexuality for adolescents
      and young adults living with and beyond cancer. For patients, the interruption to
      normal socialization creates gaps in information and experience that potentially
      hinder development. In clinical practice, conversations relating to sexual
      consequences of illness or treatment are rare, as are age-appropriate assessment
      and intervention. In service design, the collaborative approach of oncofertility
      has yet to be replicated for sexuality. This paper considers how these obstacles
      can be overcome through local service development to address unmet need and
      promote sexual well-being for this group of patients.

PMID- 30216639
TI  - Using max standardized uptake value from positron emission tomography to assess
      tumor responses after lung stereotactic body radiotherapy for different
      prescriptions.
AB  - PURPOSE: To retrospectively investigate tumor responses of lung SBRT patients for
      different prescriptions. To analyze the relation between optimal biologically
      equivalent dose (BED) and tumor responses. METHODS AND MATERIALS: Tumor responses
      after lung SBRT were compared by examining 48 treatments used four prescriptions.
      This study used simplified tumor response criteria: (a) Complete Response (CR) -
      post max SUV (SUVpost ) after SBRT in the treated tumor region was almost the
      same as the SUVs in the surrounding regions; (b) Partial Response (PR) - SUVpost
      was smaller than previous max SUV (SUVpre ), but was greater than the SUVs in the
      surrounding regions; (c) No Response (NR) - SUVpost was the same as or greater
      than SUVpre . Some SUVpost reported as mild or favorable responses were
      classified as CR/PR. BED calculated using alpha/beta of 10 Gy were analyzed with
      assessments of tumor responses for SBRT prescriptions. RESULTS: For the
      prescriptions (9 Gy * 5, 10 Gy * 5, 11 Gy * 5, and 12 Gy * 4) historically
      recommended by RTOG, we observed that higher BED10 and lower tumor volume would
      achieve a higher complete response rate. The highest complete response rate was
      observed for smallest tumor volume (PTVave  = 6.8 cc) with higher BED10 (105.6)
      of 12 Gy * 4 prescription. For 11 Gy * 5 prescription, the BED10 (115.5) was the
      highest, but its complete response rate (58%) was lower than 79% of 12 Gy * 4
      prescription. We observed the PTVave of 11 Gy * 5 prescription was more than
      double of the PTVave of 12 Gy * 4 prescription. For the same lung SBRT
      prescription (BED10  > 100) earlier staging tumor had more favorable local
      control. CONCLUSION: We demonstrated post max SUV read from PET/CT could
      efficiently and accurately assess tumor response after lung SBRT. Although SBRT
      with prescriptions resulting in a BED10  > 100 experienced favorable tumor
      responses for early staging cancer, escalation of BED10 to higher levels would be
      beneficial for lung cancer patients with later staging and larger volume tumors.

PMID- 30216643
TI  - Near-infrared emitting Ca5 (PO4 )3 Cl:Eu2+ ,Nd3+ phosphor for modification of the
      solar spectrum.
AB  - Intense near-infrared (NIR) emitting phosphors Ca5 (PO4 )3 Cl:Eu2+ ,Nd3+ were
      synthesized using a conventional solid-state reaction method and characterized
      using X-ray diffraction, reflectance, photoluminescence (PL) emission and PL
      excitation (PLE) spectroscopy, and PL lifetime measurements. The emission could
      be excited by broad band radiation in the nUV region as a consequence of Eu2+ 
      >Nd3+ energy transfer. The efficiency of Eu2+ ->Nd3+ energy transfer was as high
      as 80.8%. Two components observed in the decay curves could be identified with
      Eu2+ substituting different Ca2+ sites. Eu2+ lifetimes were shortened after Nd3+
      doping. Near infra-red emission intensity was limited by Nd3+ ->Nd3+ energy
      transfer and the consequent concentration quenching. The critical distance for
      Nd3+ ->Nd3+ energy transfer was estimated to be 11.41 A. Absorption of nUV
      radiations followed by conversion to NIR indicated the potential application in
      solar photovoltaics.

PMID- 30216644
TI  - Insulin-dependent diabetes: A chronic complication to acute pancreatitis in
      childhood acute lymphoblastic leukemia.
AB  - Pancreatitis is a frequent toxicity to acute lymphoblastic leukemia (ALL)
      treatment, significantly associated with asparaginase use, and may be followed by
      severe complications such as acute hyperglycaemia, need for mechanical
      ventilation, pseudocysts, and death. Here, we provide novel data on seven
      patients diagnosed with diabetes after pancreatitis and still requiring insulin
      treatment after a median follow-up of 4.2 years (range: 1.7-9.2). We describe the
      clinical course of pancreatitis and illustrate the association between pancreatic
      pseudocysts, older age, and development of insulin-dependent diabetes. Together,
      this study documents the persisting burden of pancreatitis in childhood ALL and
      underlines the need for plasma glucose level monitoring.

PMID- 30216646
TI  - Happy Birthday Ignac Semmelweiss! Now, Let's All Wash Our Hands!

PMID- 30216645
TI  - Heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to
      pharmorubicin by promoting autophagy via PI3K/Akt pathway.
AB  - BACKGROUND: Concerns about breast cancer had become the most dangerous cancer to
      women over the world, more and more anti-cancer agents are developed to treat
      this malignancy. Pharmorubicin is a cytotoxic drug, widely used in the treatment
      of breast cancer, but its role is limited because of chemoresistance produced by
      cells. This study focused on exploring the influence of autophagy on the
      resistance of pharmorubicin in breast cancer cells. METHODS: The cell survival of
      breast cancer cells was detected by MTT. The mRNA expression of heme oxygenase-1
      (HO-1) was tested by qRT-PCR. The protein expression of HO-1, autophagic proteins
      (LC3-I,LC3-II and Beclin-1), PI3K and Akt was detected by Western blot. Cell
      autophagy was examined by Cyto-ID Autophagy Detection Kit. RESULTS: After being
      treated with pharmorubicin, the expression of HO-1 and autophagy related proteins
      was significantly enhanced, but the cell survival ratio in the two cell lines
      decreased. After autophagy was inhibited, HO-1 expression in two cells was down
      regulated. When pharmorubicin-resistant cells were transfected with si-HO-1, the
      cell survival decreased and the protein expression of HO-1, autophagic proteins
      (LC3-II/LC3-I and Beclin-1) as well as autophagy were all down-regulated, while
      in pharmorubicin-resistant cells transfected with pcDNA3.1-HO-1, the results were
      reverse. When the PI3K or Akt was inhibited, PI3K, p-Akt, HO-1, autophagic
      proteins and autophagy were decreased remarkably. CONCLUSION: It was proved that
      HO-1 induction mediated chemoresistance of pharmorubicin in breast cancer cells
      by promoting autophagy via PI3K/Akt pathway.

PMID- 30216647
TI  - Seasonal influenza immunisation: Strategies for older adults.
AB  - Adults over the age of 60-65 years suffer disproportionally from seasonal
      influenza, experiencing high rates of complications, exacerbation of underlying
      medical comorbidities, and excess mortality. Thus, older adults are an important
      priority for influenza immunisation campaigns. Unfortunately, older adults
      generally display lower immune responses to standard influenza vaccines because
      of immunosenescence, with resulting suboptimal vaccine effectiveness. Thus, the
      development of improved vaccines that heighten immune responses and improve
      effectiveness is an important medical need. To this end, enhanced influenza
      vaccines specifically targeting this age group have been developed, which seek to
      overcome the inherent limitations in the immune responses of older adults. Both
      the licensed high-dose trivalent influenza vaccine (hdTIV) containing fourfold
      higher antigen contents than standard vaccine, and the MF59(r) -adjuvanted
      trivalent influenza vaccine (aTIV) have been proven to be safe and well-tolerated
      while enhancing the immune response. Healthcare providers for populations of
      older adults should be advised to routinely use these enhanced influenza vaccines
      in seasonal immunisation campaigns to provide improved immunity against influenza
      and its consequences in this particularly susceptible age group.

PMID- 30216648
TI  - Risk of hypoglycaemia in people aged >=65 years receiving linagliptin: pooled
      data from 1489 individuals with type 2 diabetes mellitus.
AB  - AIMS: To investigate the risk of hypoglycaemia in people aged >=65 years with
      type 2 diabetes mellitus (T2DM) treated with linagliptin, in the largest pooled
      analysis performed to date. MATERIALS AND METHODS: One thousand four hundred and
      eighty-nine patients aged >=65 years with T2DM were pooled from 11 randomised,
      double-blind, parallel group, placebo-controlled trials evaluating linagliptin 5
      mg alone, or in addition to various background therapies. The primary safety
      endpoint was the incidence of investigator-defined hypoglycaemia. RESULTS: There
      was no significant difference in the risk of hypoglycaemia between linagliptin
      and placebo in the all-patient population at 24 weeks (hazard ratio [HR] 1.07;
      95% confidence interval [CI]: 0.84, 1.36; P = 0.5943)-despite significant (P <
      0.0001) improvements in glycaemic control-and 1 year (HR 1.02; 95% CI: 0.81,
      1.27; P = 0.8803). Similar findings were observed for linagliptin vs placebo in
      subgroup analyses by background medication (eg, sulphonylureas (SUs) and/or
      insulin vs no such drugs), age, baseline glycated haemoglobin (HbA1c), ethnicity,
      and baseline estimated glomerular filtration rate. Patients with a baseline HbA1c
      >=7.5% had significantly higher odds of achieving HbA1c <7.5% without
      hypoglycaemia in the linagliptin group compared with placebo at 24 weeks (34.1%
      vs 13.7%; 95% CI: 2.04, 4.12; P < 0.0001). CONCLUSIONS: This pooled analysis
      indicates that linagliptin was effective in treating older people with T2DM
      towards their HbA1c targets with a favourable safety and tolerability profile and
      low risk of hypoglycaemia. The safety profile was maintained even on background
      therapies with known risk of hypoglycaemia, such as insulin and SU.

PMID- 30216650
TI  - Quantifying the link between long-term condition (LTC) patient experience in
      primary care and their clinical outcomes as measured by the National Diabetes
      Audit.

PMID- 30216649
TI  - Incidence and in-hospital outcomes of Clostridium difficile infection among type
      2 diabetes patients in Spain.
AB  - AIM: To examine incidence and in-hospital outcomes of Clostridium difficile
      infection (CDI) among patients with type 2 diabetes (T2DM); compare clinical
      variables among T2DM patients with matched non-T2DM patients hospitalised with
      CDI and identify factors associated with in-hospital mortality (IHM) among T2DM
      patients. METHODS: We performed a retrospective study using the Spanish National
      Hospital Discharge Database, 2001-2015. We included patients that had CDI as
      primary or secondary diagnosis in their discharge report. For each T2DM patient,
      we selected a gender, age, readmission status and year-matched non-diabetic
      patient. RESULTS: We identified 44 695 patients with CDI (21.19% with T2DM). We
      matched 3040 and 5987 couples with a primary and secondary diagnosis of CDI,
      respectively. Incidence of CDI was higher in T2DM patients (IRR per hospital
      admission 1.12; 95% CI 1.09-1.14, IRR per population 1.26; 95% CI 1.22-1.29). IHM
      decreased over time in T2DM and non-T2DM patients (from 15.36% and 13.35%, in
      2001-2003 to 10.36% and 11.73% in 2013-2015), despite a concomitant increase in
      CDI diagnoses overtime. Among those with CDI as secondary diagnosis IHM was
      higher in nondiabetic 16.17% than in T2DM patients 13.19% (P < 0.001). In T2DM
      patients higher mortality rates were associated with older age, comorbidities,
      severe CDI, and readmission. Primary diagnosis of CDI was associated with lower
      IHM (OR 0.71; 95% CI 0.60-0.84) than secondary diagnosis. CONCLUSIONS: Incidence
      of CDI was higher in T2DM patients. IHM decreased over time, regardless of the
      existence or not of T2DM. IHM was significantly lower in T2DM patients with CDI
      as primary diagnosis than non diabetic patients.

PMID- 30216651
TI  - Thyroid function in elderly people: The role of subclinical thyroid disorders in
      cognitive function and mood alterations.

PMID- 30216652
TI  - Very long-term molecular follow-up of minimal residual disease in patients with
      neuroblastoma.
AB  - In high-risk neuroblastoma (HR-NB), the clinical significance of long-term
      minimal residual disease (MRD) monitoring using quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) for neuroblastoma mRNAs has not
      been investigated. We report long-term MRD follow-ups of four patients with HR-NB
      throughout the disease (diagnosis, remission, and relapse) and treatment course
      (chemotherapy, autologous and allogeneic stem cell transplantation, and donor
      lymphocyte and natural killer cell infusions). The results showed the stability
      of mRNA marker expression after different treatments and demonstrated their
      validity to predict relapse and assess therapeutic response. This opens up the
      possibility of investigating the utility of long-term molecular monitoring of MRD
      in prospective multicenter studies.

PMID- 30216653
TI  - Mesenchymal stromal cell potency to treat acute kidney injury increased by
      ultrasound-activated interferon-gamma/interleukin-10 axis.
AB  - Mesenchymal stromal cell (MSC) therapies combined with renal pulsed focused
      ultrasound (pFUS) pretreatment increase MSC homing and improve cisplatin-induced
      acute kidney injury (AKI) better than MSC alone. However, mechanisms underlying
      improved outcomes remain unknown. We hypothesize pFUS up-regulates renal
      interferon-gamma (IFNgamma) and stimulates MSC to produce interleukin-10 (IL-10)
      after migrating to kidneys. To demonstrate initially, MSC cultured with IFNgamma
      up-regulated IL-10. More MSC-derived IL-10 was detected in kidneys when IFNgamma
      stimulated MSC were infused and they improved AKI better than unstimulated MSC.
      Next, IFNgamma-knockout mice with AKI received pFUS+MSC, but MSC-derived IL-10
      expression and AKI were similar to using MSC alone. AKI in wild-type mice
      receiving pFUS and IL-10-deficient MSC was also unimproved compared to
      administering IL-10-deficient MSC alone. Indoleamine 2,3-dioxygenase (IDO), an
      anti-inflammatory enzyme up-regulated in MSC by IFNgamma, was up-regulated during
      AKI, but was not further elevated in MSC from pFUS-treated kidneys, suggesting
      that IDO is not involved in improved AKI healing by pFUS+MSC. These data suggest
      IFNgamma is up-regulated by pFUS and after i.v.-infused MSC home to pFUS-treated
      kidneys, IFNgamma stimulates additional IL-10 production by MSC to improve AKI.
      Analogous mechanisms of ultrasound-treated tissue microenvironments stimulating
      therapeutic MSC may exist in other pathologies where adjuvant ultrasound
      techniques are successful.

PMID- 30216654
TI  - Planned delivery route of preterm breech singletons, and neonatal and 2-year
      outcomes: a population-based cohort study.
AB  - OBJECTIVE: To assess whether planned route of delivery is associated with
      perinatal and 2-year outcomes for preterm breech singletons. DESIGN: Prospective
      nationwide population-based EPIPAGE-2 cohort study. SETTING: France, 2011.
      SAMPLE: Three hundred and ninety women with breech singletons born at 26-34 weeks
      of gestation after preterm labour or preterm prelabour rupture of membranes.
      METHODS: Propensity-score analysis. MAIN OUTCOME MEASURES: Survival at discharge,
      survival at discharge without severe morbidity, and survival at 2 years of
      corrected age without neurosensory impairment. RESULTS: Vaginal and caesarean
      deliveries were planned in 143 and 247 women, respectively. Neonates with planned
      vaginal delivery and planned caesarean delivery did not differ in survival (93.0
      versus 95.7%, P = 0.14), survival at discharge without severe morbidity (90.4
      versus 89.9%, P = 0.85), or survival at 2 years without neurosensory impairment
      (86.6 versus 91.6%, P = 0.11). After applying propensity scores and assigning
      inverse probability of treatment weighting, as compared with planned vaginal
      delivery, planned caesarean delivery was not associated with improved survival
      (odds ratio, OR 1.31; 95% confidence interval, 95% CI 0.67-2.59), survival
      without severe morbidity (OR 0.75, 95% CI 0.45-1.27), or survival at 2 years
      without neurosensory impairment (OR 1.04, 95% CI 0.60-1.80). Results were similar
      after matching on propensity score. CONCLUSIONS: No association between planned
      caesarean delivery and improved outcomes for preterm breech singletons born at 26
      34 weeks of gestation after preterm labour or preterm prelabour rupture of
      membranes was found. The route of delivery should be discussed with women,
      balancing neonatal outcomes with the higher risks of maternal morbidity
      associated with caesarean section performed at low gestational age.

PMID- 30216656
TI  - The Transformative and Versatile Role of Cellulose Nanomaterials in Templating
      and Shaping Multiscale Mesostructured Ceramics.
AB  - The transformative and versatile role of cellulose nanomaterials (CNMs) as an
      enabling technology in the preparation of multiscale mesostructured ceramics,
      with pore sizes in the meso- (2-50 nm) and macroporosity (above 50 nm) range with
      controlled porous architecture across the structure is explored. CNMs have
      revolutionized functional advanced materials concepts and technology by using
      natural resources to derive superb properties. Its unique chemical and physical
      properties have inspired its exploitation as a reinforcement agent, stimuli
      responsive tool, and templating agent mostly for biologic and polymeric
      materials, as well as for metals and ceramics. CNMs can act as a sacrificial
      filler templating agent, a surface modifier agent, and as an aid for shaping
      macrostructures into bulk samples. A deep knowledge of the synergistic
      interaction mechanisms between CNMs and ceramic particles to assemble them in
      solution and into solid structures is key to advance this technology, and to
      develop a predictive understanding of synthesis and processing mechanisms that
      relates morphology evolution, processing, and final physical properties. The
      potential ease of processing and versatility of CNMs for functional ceramic
      technology, intimately linked to the CNMs' nature and properties, will make a
      significant impact with respect to the current state of the art.

PMID- 30216657
TI  - Dietary intake in youth with prader-willi syndrome.
AB  - Dietary management is important to prevent severe obesity in individuals with
      Prader-Willi syndrome (PWS); however, few studies have examined dietary intake
      and quality in youth with PWS. Our objective was to estimate intake of essential
      nutrients and diet quality in youth with PWS compared to those without PWS. Three
      day food records were used to estimate intake of energy, nutrients, nutrient
      density, foods, and adherence to healthy eating guidelines. Data were presented
      as medians and interquartile ranges with Mann-Whitney U and Fisher's test used to
      compare between groups with p < .05 considered significant. Youth with (n = 23)
      and without (n = 23) PWS were similar in age and sex distribution. The PWS group
      had a lower energy intake (p <= .001), higher nutrient density (p = .003), and
      better adherence to guidelines (p = .007) compared to the control group. The
      proportion with nutrient intake from food below Estimated Average Requirement or
      Adequate Intake were similar between groups. Fiber, vitamin D, calcium, and
      potassium intake were below recommendations in 50% or more in both groups. The
      inclusion of supplement intake lowered the proportion below recommendations,
      except for fiber and potassium. Youth with PWS had a similar nutrient intake as
      those without PWS despite a lower energy intake, which could be attributed to
      higher diet quality. However, more than half of youth with PWS were at risk of
      inadequate fiber, vitamin D, calcium, and potassium intake. A greater emphasis on
      nutrient-dense foods would improve nutrient intake, but supplements may be
      warranted in youth with PWS who do not meet recommendations.

PMID- 30216658
TI  - Warsaw breakage syndrome: Further clinical and genetic delineation.
AB  - Warsaw breakage syndrome (WBS) is a recently recognized DDX11-related rare
      cohesinopathy, characterized by severe prenatal and postnatal growth restriction,
      microcephaly, developmental delay, cochlear anomalies, and sensorineural hearing
      loss. Only seven cases have been reported in the English literature, and thus the
      information on the phenotype and genotype of this interesting condition is
      limited. We provide clinical and molecular information on five additional
      unrelated patients carrying novel bi-allelic variants in the DDX11 gene,
      identified via whole exome sequencing. One of the variants was found to be a
      novel Saudi founder variant. All identified variants were classified as
      pathogenic or likely pathogenic except for one that was initially classified as a
      variant of unknown significance (VOUS) (p.Arg378Pro). Functional characterization
      of this VOUS using heterologous expression of wild type and mutant DDX11 revealed
      a marked effect on protein stability, thus confirming pathogenicity of this
      variant. The phenotypic data of the seven WBS reported patients were compared to
      our patients for further phenotypic delineation. Although all the reported
      patients had cochlear hypoplasia, one patient also had posterior labyrinthine
      anomaly. We conclude that while the cardinal clinical features in WBS
      (microcephaly, growth retardation, and cochlear anomalies) are almost universally
      present, the breakage phenotype is highly variable and can be absent in some
      cases. This report further expands the knowledge of the phenotypic and molecular
      features of WBS.

PMID- 30216655
TI  - A pan-cancer atlas of cancer hallmark-associated candidate driver lncRNAs.
AB  - Substantial cancer genome sequencing efforts have discovered many important
      driver genes contributing to tumorigenesis. However, very little is known about
      the genetic alterations of long non-coding RNAs (lncRNAs) in cancer. Thus, there
      is a need for systematic surveys of driver lncRNAs. Through integrative analysis
      of 5918 tumors across 11 cancer types, we revealed that lncRNAs have undergone
      dramatic genomic alterations, many of which are mutually exclusive with well
      known cancer genes. Using the hypothesis of functional redundancy of mutual
      exclusivity, we developed a computational framework to identify driver lncRNAs
      associated with different cancer hallmarks. Applying it to pan-cancer data, we
      identified 378 candidate driver lncRNAs whose genomic features highly resemble
      the known cancer driver genes (e.g. high conservation and early replication). We
      further validated the candidate driver lncRNAs involved in 'Tissue Invasion and
      Metastasis' in lung adenocarcinoma and breast cancer, and also highlighted their
      potential roles in improving clinical outcomes. In summary, we have generated a
      comprehensive landscape of cancer candidate driver lncRNAs that could act as a
      starting point for future functional explorations, as well as the identification
      of biomarkers and lncRNA-based target therapy.

PMID- 30216659
TI  - Cardioprotective cytokine interleukin-33 is up-regulated by statins in human
      cardiac tissue.
AB  - Interleukin (IL)-33 is a member of the IL-1 family and is able to act
      cardioprotective. The aim of this study was to investigate the regulation of IL
      33 by 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors
      (statins) and bisphosphonates (BPs) in human cardiac tissue. The lipophilic
      fluvastatin, simvastatin, atorvastatin, and lovastatin as well as the nitrogenous
      BPs alendronate and ibandronate, but not hydrophilic pravastatin increased IL-33
      mRNA and intracellular IL-33 protein levels in both human adult cardiac myocytes
      (HACM) and fibroblasts (HACF). Additionally, fluvastatin reduced soluble ST2
      secretion from HACM. IL-33 was also up-regulated by the general inhibitor of
      prenylation perillic acid, a RhoA kinase inhibitor Y-27632, and by latrunculin B,
      but statin-induced IL-33 expression was inhibited by mevalonate, geranylgeranyl
      pyrophosphate (GGPP) and RhoA activator U-46619. The IL-33 promoter was 2.3-fold
      more accessible in statin-treated HACM compared to untreated cells (P = 0.037).
      In explanted hearts of statin-treated patients IL-33 protein was up-regulated as
      compared with the hearts of non-statin-treated patients (P = 0.048). As IL-33 was
      previously shown to exert cardioprotective effects, one could speculate that such
      up-regulation of IL-33 expression in human cardiac cells, which might happen
      mainly through protein geranylgeranylation, could be a novel mechanism
      contributing to known cardioprotective effects of statins and BPs.

PMID- 30216662
TI  - Lithography-Free Electrochemical Patterning of Conductive Substrates with Metal
      Oxides.
AB  - Reactive interface patterning promoted by lithographic electrochemistry serves as
      a facile method for generating submicron structures on conductive substrates. A
      binary-potential step applied to a metal layer with a resist overlayer allows
      silicon to be patterned with metal oxides. In this study, the role and influence
      of the resist overlayer on the uniformity of pattern formation are examined. The
      ability of the resist to detach from the underlying metal is a critical
      determinant of pattern geometry. By choosing an appropriate resist, large
      patterns with submicron precision are generated quickly by the application of the
      binary-potential steps. From this information, a lithography-free approach to
      generating identical patterns is achieved with simple resists such as that
      furnished from a lacquer-water emulsion, thus greatly simplifying the patterning
      of silicon with metal oxide catalysts.

PMID- 30216661
TI  - Endoflip vs high-definition manometry in the assessment of fecal incontinence: A
      data-driven unsupervised comparison.
AB  - BACKGROUND: How much anal sphincter dysfunction contributes to fecal incontinence
      (FI) is not clear. High-definition anorectal manometry (HDAM) and functional
      luminal imaging probe (Endoflip) are two new techniques to study anal sphincter
      function. AIMS: The goal was to compare the diagnostic utility of HDAM and
      Endoflip using optimal feature(s) in each modality for FI diagnosis. METHODS:
      Blinded classification was carried out on 70 female subjects (32 FI & 38
      controls), using 3 prominent machine-learning clustering techniques, with 3
      distance metrics. For HDAM, descriptive statistics, shape, and textural features
      characterizing the spatial relationship of pixels in the HDAM high-pressure zone,
      and for Endoflip, permutations of pressure and CSA combinations (ie,
      multiplication, division, or individually) at rest and squeeze were tested.
      RESULTS: Intramodality: (a) Endoflip: Best clustering was obtained using the
      combination of the ratio of CSA over pressure at 40 and 50 mL at rest, which had
      significantly better specificity (P < 0.001) than using only pressure at 50 mL,
      no difference in sensitivity (P = 0.68). (b) HDAM: clustering using textural
      information at rest had significantly higher specificity compared to using only
      the maximal pressure at rest (P < 0.001). Intermodality: Clustering results using
      optimal features were not significantly different with respect to sensitivity or
      specificity (P > 0.05). Optimal Endoflip feature set differed significantly in
      specificity compared to HDAM maximal pressure at both rest (P < 0.001) and
      squeeze (P < 0.001). CONCLUSION: Defective anal closure function is fairly
      sensitive and highly specific in diagnosing FI. Using optimal feature sets, HDAM
      and Endoflip perform in a similar fashion in diagnosing FI, but are not
      complementary.

PMID- 30216663
TI  - Erosive tooth wear: Knowledge among young adults and their preferred information
      sources.
AB  - OBJECTIVES: The aim of this study was to learn more about levels of knowledge
      relating to erosive tooth wear and about the most desirable way of disseminating
      dental information among young adults. METHODS: The research was a cross
      sectional study of 331 young adults (20-25 years old) attending 25 dental care
      practices. Participants were asked to fill out a questionnaire with questions
      about their background, knowledge relating to erosive tooth wear and the
      preferred way of acquiring information about erosive tooth wear. RESULTS: The
      results showed that there are gaps in the knowledge of young adults about erosive
      tooth wear. The knowledge score depended on educational level and dental
      information received in the past. The preferred way of acquiring information was
      chairside information from an oral health care professional complemented by
      tailored information in writing. CONCLUSION: There is a lack of knowledge among
      young adults about erosive tooth wear. They prefer to receive information from
      the oral health care professionals accompanied by tailored information in
      writing. Further research should focus on developing this tailored information in
      line with the advice given by the oral health care professional.

PMID- 30216664
TI  - Electrophoretic deposition of lawsone loaded bioactive glass (BG)/chitosan
      composite on polyetheretherketone (PEEK)/BG layers as antibacterial and bioactive
      coating.
AB  - In this study, chitosan/bioactive glass (BG)/lawsone coatings were deposited by
      electrophoretic deposition (EPD) on polyetheretherketone (PEEK)/BG layers
      (previously deposited by EPD on 316-L stainless steel) to produce bioactive and
      antibacterial coatings. First, the EPD of chitosan/BG/lawsone was optimized on
      stainless steel in terms of suspension stability, homogeneity and thickness of
      coatings. Subsequently, the optimized EPD parameters were used to produce
      bioresorbable chitosan/bioactive glass (BG)/lawsone coatings on PEEK/BG layers.
      The produced layered coatings were characterized in terms of composition,
      microstructure, corrosion resistance, in vitro bioactivity, drug release kinetics
      and antibacterial activity. Ultraviolet/Visible (UV/VIS) spectroscopic analyses
      confirmed the release of lawsone from the coatings. Moreover, the deposition of
      chitosan/BG coatings was confirmed by Scanning Electron Microscopy (SEM) and
      Fourier Transform Infrared spectroscopy (FTIR). The coated specimens presented
      higher corrosion resistance (10 times) in comparison to that of bare 316-L
      stainless steel and showed convenient wettability for initial protein attachment.
      The presence of lawsone in the top layer provided antibacterial effects against
      Staphylococcus carnosus. Moreover, the developed coatings formed apatite-like
      crystals upon immersion in simulated body fluid, indicating the possibility of
      achieving close interaction between the coating surface and bone. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3111-3122, 2018.

PMID- 30216665
TI  - Latent trajectories of infant breast milk consumption in the United States.
AB  - Patterns of breastfeeding over time are not currently well understood. Limited
      qualitative and quantitative evidence suggests that there may be latent subgroups
      of mothers in the United States following very different trajectories of breast
      milk provision for their infants. This study used a quantitative modelling method
      (group-based trajectory modelling) to identify and describe these subgroups.
      Using data from the Infant Feeding Practices Study II (n = 3,023), the authors
      identified four distinct trajectories of breastfeeding intensity, each of which
      included a substantial subset of the total sample. A model with four groups fit
      the data well by objective and conceptual standards. Bivariate associations were
      analysed, and significant difference between trajectory group membership was
      found on an array of maternal and family determinants, including maternal
      demographics, hospital experience, and psychosocial resources, as well as on
      postweaning perceptions. These associations were used to create group profiles
      for each subgroup. Controlling for sociodemographic covariates, we also found
      that trajectory membership was significantly associated with several health
      outcomes for the target child 6 years later, including certain infections, picky
      eating, and health care utilization; trajectory group membership was also
      associated with maternal breastfeeding of subsequent children and maternal body
      mass index (BMI) at Year 6. Child BMI z-score and maternal breast cancer
      diagnosis were not significantly different across trajectory groups after
      accounting for confounding covariates, nor was time missed from school for the
      target child. Though exploratory, the initial identification and description of
      these four subgroups suggest future directions using breastfeeding trajectory
      methods, with potential implications for measurement, intervention development,
      and targeting.

PMID- 30216660
TI  - PCAF fine-tunes hepatic metabolic syndrome, inflammatory disease, and cancer.
AB  - The P300/CBP-associating factor (PCAF), a histone acetyltransferase, is involved
      in metabolic and pathogenic diseases, particularly of the liver. The effects of
      PCAF on fine-tuning liver diseases are extremely complex and vary according to
      different pathological conditions. This enzyme has dichotomous functions,
      depending on differently modified sites, which regulate the activities of various
      enzymes, metabolic functions, and gene expression. Here, we summarize the most
      recent findings on the functions and targets of PCAF in various metabolic and
      immunological processes in the liver and review these new discoveries and models
      of PCAF biology in three areas: hepatic metabolic syndrome, inflammatory disease,
      and cancer. Finally, we discuss the potential implications of these findings for
      therapeutic interventions in liver diseases.

PMID- 30216666
TI  - Air-Stable and Self-Driven Perovskite Photodiodes with High On/Off Ratio and
      Swift Photoresponse.
AB  - Recent years have witnessed rapid developments in organic-inorganic hybrid
      perovskites, among which 2D Ruddlesden-Popper (RP) perovskites stand out due to
      their outstanding ambient stability. In photodetector applications, 2D RP
      perovskites are mostly limited to lateral device configuration because of their
      preferred in-plane charge transportation within quantum well structures. In this
      work, the low-temperature solution construction of 2D RP perovskite-based
      photodiodes in vertical device architecture is demonstrated. The paradigm
      phenylethylamine (PEA) spacer cation-based 2D perovskites are fabricated and
      optimized by exploiting a combination of a NH4 Cl additive and dimethyl sulfoxide
      solvent (DMSO) solvent. They show increased crystallinity, extended
      photoluminescence lifetimes, and importantly a generation of 3D phases embedded
      within 2D perovskites, which efficiently promotes charge transfer. As a result,
      the photodetectors exhibit a high on/off ratio up to 2 * 104 , a large
      photocurrent of 0.34 mA cm-2 , and rapid rise (5.8 ms) and decay time (4.6 ms).
      Of critical importance is the outstanding film/device stabilities demonstrated by
      storage in air (at 25  degrees C with 60% relative humidity) for 15 days as well
      as under UV illumination for 1.5 h and after 1500 bending cycles on flexible
      substrate.

PMID- 30216667
TI  - All Cats are Gray in the Dark: Enrichment/Depletion Approaches for Biomarker
      Discovery on Felis catus Plasma.
AB  - In veterinary medicine, assay performance is often affected by the lack of
      species-specific diagnostic tools. Reliable biomarkers might be identified by
      investigating biological fluids of the species of interest, but protein sequence
      databases are often incomplete and human-specific devices for reducing sample
      complexity might fail when applied to animal plasma. Here, seven commercial
      methods based on different capturing agents (anti-human antibodies, affinity
      ligands, mixture of antibodies and ligands, and combinatorial peptide ligand
      libraries) are applied to cat plasma and evaluated in terms of yield, identified
      proteins/ peptides, and relative abundance by high-resolution shotgun proteomics
      and label-free quantitation. As a result, anti-human antibody-based methods are
      unsatisfactory. Most fail in reducing albumin and immunoglobulins, and some lead
      to a substantial removal of other highly abundant proteins, probably because of
      nonspecific interactions. A protein A/dye ligand-based method is efficient in
      reducing immunoglobulins, fibrinogen, and apolipoprotein A1 and A2, but not
      albumin, and protein identifications do not increase. Only peptide ligand
      libraries flatten the dynamic range, and increased protein identification
      (59.0%). Albumin and immunoglobulins are successfully depleted (60.7% and 35.9%,
      respectively). Although further studies will be required for reinforcing our
      observations, this work can provide a useful guide for cat plasma pretreatment in
      biomarker discovery studies.

PMID- 30216668
TI  - Millerite Core-Nitrogen-Doped Carbon Hollow Shell Structure for Electrochemical
      Energy Storage.
AB  - Nickel sulfides have drawn much attention with the benefits of a high redox
      activity, high electrical conductivity, low cost, and fabrication ease; however,
      these metal sulfides are susceptible to mechanical degradation regarding their
      cycling performance. Conversely, hollow carbon shells exhibit a substantial
      electrochemical steadiness in energy storage applications. Here, the design and
      development of a novel millerite core-nitrogen-doped carbon hollow shell (NiS-NC
      HS) structure for electrochemical energy storage is presented. The nitrogen-doped
      carbon hollow shell (NC HS) protects against the degradation and the millerite
      core aggregation, giving rise to an excellent rate capability and stability
      during the electrochemical charging-discharging processes, in addition to
      improving the NiS-NC HS conductivity. The NiS-NC HS/18h supercapacitor electrode
      displays an outstanding specific capacitance of 1170.72 F g-1 (at 0.5 A g-1 ) and
      maintains 90.71% (at 6 A g-1 ) of its initial capacitance after 4000 charge
      discharge cycles, owing to the unique core-shell structure. An asymmetric
      supercapacitor device using NiS-NC HS and activated-carbon electrodes exhibits a
      high power and energy density with a remarkable cycling stability, maintaining
      89.2% of its initial capacitance after 5000 cycles.

PMID- 30216670
TI  - The New Face of the Lipid Droplet: Lipid Droplet Proteins.
AB  - The lipid droplet (LD) is an organelle with vital functions found in nearly all
      organisms. LD proteomic research has provided fundamentally important insights
      into this organelle's functions. The review provides a summary of LD proteomic
      studies conducted across diverse organisms and cell and tissue types. The
      accumulated proteomic data are reviewed for evidence of a protein targeting
      mechanism for the organelle. The hypotheses for several specific localization
      mechanisms based on what is known about targeting mechanisms for other organelles
      and vesicles are provided. Although the nature of the mechanism is not known, the
      functional data demonstrate that the targeting mechanism and, indeed, the
      organelle itself, is conserved from prokaryotes to eukaryotes. It is hoped that
      the review will help inspire further research leading to novel discoveries in the
      field.

PMID- 30216669
TI  - MaSS-Simulator: A Highly Configurable Simulator for Generating MS/MS Datasets for
      Benchmarking of Proteomics Algorithms.
AB  - Mass Spectrometry (MS)-based proteomics has become an essential tool in the study
      of proteins. With the advent of modern MS machines huge amounts of data is being
      generated, which can only be processed by novel algorithmic tools. However, in
      the absence of data benchmarks and ground truth datasets algorithmic integrity
      testing and reproducibility is a challenging problem. To this end, MaSS-Simulator
      has been presented, which is an easy to use simulator and can be configured to
      simulate MS/MS datasets for a wide variety of conditions with known ground
      truths. MaSS-Simulator offers many configuration options to allow the user a
      great degree of control over the test datasets, which can enable rigorous and
      large- scale testing of any proteomics algorithm. MaSS-Simulator is assessed by
      comparing its performance against experimentally generated spectra and spectra
      obtained from NIST collections of spectral library. The results show that MaSS
      Simulator generated spectra match closely with real-spectra and have a relative
      error distribution centered around 25%. In contrast, the theoretical spectra for
      same peptides have relative-error distribution centered around 150%. MaSS
      Simulator will enable developers to specifically highlight the capabilities of
      their algorithms and provide a strong proof of any pitfalls they might face.
      Source code, executables, and a user manual for MaSS-Simulator can be downloaded
      from https://github.com/pcdslab/MaSS-Simulator.

PMID- 30216671
TI  - Antigenic evolution of H3N2 influenza A viruses in swine in the United States
      from 2012 to 2016.
AB  - BACKGROUND: Six amino acid positions (145, 155, 156, 158, 159, and 189, referred
      to as the antigenic motif; H3 numbering) in the globular head region of
      hemagglutinin (HA1 domain) play an important role in defining the antigenic
      phenotype of swine Clade IV (C-IV) H3N2 IAV, containing an H3 from a late 1990s
      human-to-swine introduction. We hypothesized that antigenicity of a swine C-IV H3
      virus could be inferred based upon the antigenic motif if it matched a previously
      characterized antigen with the same motif. An increasing number of C-IV H3 genes
      encoding antigenic motifs that had not been previously characterized were
      observed in the U.S. pig population between 2012 and 2016. OBJECTIVES: A broad
      panel of contemporary H3 viruses with uncharacterized antigenic motifs was
      selected across multiple clades within C-IV to assess the impact of HA1 genetic
      diversity on the antigenic phenotype. METHODS: Hemagglutination inhibition (HI)
      assays were performed with isolates selected based on antigenic motif, tested
      against a panel of swine antisera, and visualized by antigenic cartography.
      RESULTS: A previously uncharacterized motif with low but sustained circulation in
      the swine population demonstrated a distinct phenotype from those previously
      characterized. Antigenic variation increased for viruses with similar antigenic
      motifs, likely due to amino acid substitutions outside the motif. CONCLUSIONS:
      Although antigenic motifs were largely associated with antigenic distances,
      substantial diversity among co-circulating viruses poses a significant challenge
      for effective vaccine development. Continued surveillance and antigenic
      characterization of circulating strains is critical for improving vaccine efforts
      to control C-IV H3 IAV in U.S. swine.

PMID- 30216672
TI  - Mother's dietary diversity and association with stunting among children <2 years
      old in a low socio-economic environment: A case-control study in an urban care
      setting in Dhaka, Bangladesh.
AB  - Mothers are often responsible for preparing nutritious foods in their households.
      However, the quality of mother's diets is often neglected, which may affect both
      mother's and child's nutrition. Because no single food contains all necessary
      nutrients, diversity in dietary sources is needed to ensure a quality diet. We
      aimed to study the association between mother's dietary diversity and stunting in
      children <2 years attending Dhaka Hospital of icddr,b, a diarrhoeal disease
      hospital in Dhaka, Bangladesh. A case-control study (n = 296) was conducted from
      November 2016 to February 2017. Data were collected from mothers of stunted
      children <2 years (length-for-age z score [LAZ] < -2) as "cases" and nonstunted
      (LAZ >= -1) children <2 years as "controls." Mothers were asked to recall
      consumption of 10 defined food groups 24 hr prior to the interview as per
      Guidelines for Minimum Dietary Diversity for Women. Among the mothers of cases,
      58% consumed <5 food groups during the last 24 hr, compared with 45% in control
      mothers (P = 0.03). Children whose mothers consumed <5 food groups were 1.7 times
      more likely to be stunted than children whose mothers consumed >=5 food groups (P
      = 0.04). Intake of food groups such as pulses, dairy, eggs, and vitamin A rich
      fruit was higher in control mothers. Proportion of mother's illiteracy, short
      stature, monthly family income <BDT 11,480, absence of bank account, and poor
      sanitation was also found to be higher in stunted group. Further study
      particularly intervention or longitudinal study to see the causality of mother's
      dietary diversity with child stunting is recommended.

PMID- 30216673
TI  - Microstructural Degradation of Ni-Rich Li[Nix Coy Mn1 -x-y ]O2 Cathodes During
      Accelerated Calendar Aging.
AB  - Because electric vehicles (EVs) are used intermittently with long resting periods
      in the fully charged state before driving, calendar aging behavior is an
      important criterion for the application of Li-ion batteries used in EVs. In this
      work, Ni-rich Li[Nix Coy Mn1 -x-y ]O2 (x = 0.8 and 0.9) cathode materials with
      high energy densities, but low cycling stabilities are investigated to
      characterize their microstructural degradation during accelerated calendar aging.
      Although the particles seem to maintain their crystal structures and
      morphologies, the microcracks which develop during calendar aging remain even in
      the fully discharged state. An NiO-like phase rock-salt structure of tens of
      nanometers in thickness accumulates on the surfaces of the primary particles
      through parasitic reactions with the electrolyte. In addition, the passive layer
      of this rock-salt structure near the microcracks is gradually exfoliated from the
      primary particles, exposing fresh surfaces containing Ni4+ to the electrolyte.
      Interestingly, the interior primary particles near the microcracks have
      deteriorated more severely than the outer particles. The microstructural
      degradation is worsened with increasing Ni contents in the cathode materials,
      directly affecting electrochemical performances such as the reversible capacities
      and voltage profiles.

PMID- 30216675
TI  - Survival differences in nasopharyngeal carcinoma among racial and ethnic minority
      groups in the United States: A retrospective cohort study.
AB  - OBJECTIVE: The literature on nasopharyngeal carcinoma survival in the United
      States has focused mostly on Whites or Asians and not much is known about
      survivorship in other minority racial and ethnic groups. We aimed to determine
      the disease-specific survival rate and prognostic factors for nasopharyngeal
      carcinoma survival across the minority United States population. DESIGN: A
      retrospective cohort study. SETTING: The Surveillance, Epidemiology and End
      Results (SEER) 13 database from 1992 to 2014 was queried for adult cases of
      nasopharyngeal carcinoma (n = 2549). PARTICIPANTS: Eligible cases were Blacks,
      Hispanics, Asians/Pacific Islanders, American Indians/Alaska Natives; White
      patients were excluded. MAIN OUTCOMES MEASURE: A multivariable competing risk
      survival analysis yielded hazard ratios (HR) for competing mortality and was used
      to identify independent prognostic factors for survival. RESULTS: Non-Hispanic
      American Indians/Alaska Natives consistently had the worst cause-specific
      survival of any group and that non-Hispanic Asians/Pacific Islanders consistently
      had the best survival (P < 0.001). Even after adjusting for other poor prognostic
      factors in the study, including older age, keratinising histology, and lack of
      radiation treatment, non-Hispanic American Indians/Alaska Natives had more than
      double hazards of death from nasopharyngeal cancer compared with non-Hispanic
      Asians/Pacific Islanders (aHR = 2.63, 95% CI 1.67, 4.13). CONCLUSIONS: There are
      disparities in nasopharyngeal carcinoma survival among racial and ethnic minority
      groups in the United States, with American Indians/Alaskan Natives faring worst.
      It is critical that future research focuses on nasopharyngeal carcinoma among
      this population to improve survivorship and mitigate cancer-related health
      disparities.

PMID- 30216674
TI  - Formation of Heterotypic Amyloids: alpha-Synuclein in Co-Aggregation.
AB  - Protein misfolding resulting in the formation of ordered amyloid aggregates is
      associated with a number of devastating human diseases. Intrinsically disordered
      proteins (IDPs) do not autonomously fold up into a unique stable conformation and
      remain as an ensemble of rapidly fluctuating conformers. Many IDPs are prone to
      convert into the beta-rich amyloid state. One such amyloidogenic IDP is alpha
      synuclein that is involved in Parkinson's disease. Recent studies have indicated
      that other neuronal proteins, especially IDPs, can co-aggregate with alpha
      synuclein in many pathological ailments. This article describes several such
      observations highlighting the role of heterotypic protein-protein interactions in
      the formation of hetero-amyloids. It is believed that the characterizations of
      molecular cross talks between amyloidogenic proteins as well as the mechanistic
      studies of heterotypic protein aggregation will allow us to decipher the role of
      the interacting proteins in amyloid proteomics.

PMID- 30216676
TI  - Prosthetics and orthotics education development in Southeast Asia.

PMID- 30216677
TI  - Should freestanding emergency departments be considered in Australia?
AB  - The concept of freestanding EDs is a popular operational model of emergency care
      in the USA. This model has been described as an emergency physician-created
      innovative solution in resolving ongoing overcrowding issues in EDs. A
      decentralised community-based emergency care model may be a solution to meet the
      increasing demand for emergency and unscheduled acute care in Australia. It may
      also help to reduce the number of acute hospital admissions through EDs. The aim
      of freestanding EDs should be to manage and discharge a cohort of patients,
      mainly in Australasian Triage Scale 3 and 4 categories, currently seen in
      hospital-based EDs. This article briefly examines the potential merits and issues
      if this concept is considered in Australia. It also provides an early proposed
      model for such EDs.

PMID- 30216678
TI  - Is there a "complementary feeding cultural core" in rural Kenya? Results from
      ethnographic research in five counties.
AB  - This investigation used data from focused ethnographic studies in five rural
      counties in Kenya to determine whether the concept of "special foods for infants
      and young children" exists in the different ethnic groups in these areas as an
      identifiable component of cultural beliefs and knowledge, as well as in practice,
      and whether they can be characterized as a "complementary feeding cultural core."
      The concept of "cultural core foods" refers to the set of foods that have a
      central role in diets of a population and, as a consequence, also have
      significant social and emotional components. We used the ethnographic cognitive
      mapping technique of "free listing" and a qualitative 24-hr recall of infants and
      young children (IYC) intake, with probing, to obtain data on caregivers' beliefs
      and behaviours. The results show that an IYC cultural food core can be identified
      in all of the counties. A related finding that supports the argument for an "IYC
      cultural core" with respect to appropriate foods for IYC is the clear cognitive
      consensus within sites about its content, although in practice, food insecurity
      and food shortage constrain household abilities to put their beliefs into
      practice. We conclude that interventions to improve IYC feeding in rural Kenya
      that build on the concept of "IYC cultural core foods" will be congruent with
      basic cultural ideas about managing IYC feeding and could take advantage of this
      cultural feature.

PMID- 30216679
TI  - Conformations and Binding Properties of Thiametoxam and Clothianidin
      Neonicotinoid Insecticides to Nicotinic Acetylcholine Receptors: The Contribution
      of sigma-Hole Interactions.
AB  - The structural features and molecular-interaction properties of thiamethoxam
      (THA) and clothianidin (CLO) - two neonicotinoids - have been investigated
      through a combined approach based on a wide range of molecular modeling methods
      and X-ray-structure observations. Despite their close chemical structures,
      significant differences are emphasized by QM (DFT), docking, molecular dynamics,
      and QM/QM' calculations. Thus, for the first time, their propensity to interact
      through chalcogen-bond interactions is highlighted. The influence of the
      surroundings on this behavior is pointed out: in CLO, an intramolecular S???N
      chalcogen bond is shown to stabilize the structure in the solid state whereas the
      interaction leads to the preferred conformations in the isolated and continuum
      solvent models for both compounds. Interestingly, this interaction potential
      appears to be used for their binding to Ac-AChBP through intermolecular S???O
      chalcogen bonds with the hydroxyl group of Tyr195. The use of a suitable level of
      theory to describe properly these interactions is underlined, the classical
      methods being unsuited to highlight these interactions. The contribution of
      halogen bonding through the chlorine atom of the chlorothiazole ring in the
      binding of the two compounds is also underlined, both in the solid state and in
      the Ac-AChBP surroundings. However, the accommodation of the two insecticides in
      the binding site leads to the fact that a halogen-bond contribution is pointed
      out only for CLO.

PMID- 30216680
TI  - Efficiency of the home cardiac rehabilitation program for adults with complex
      congenital heart disease.
AB  - OBJECTIVE: We aimed to study the efficiency and safety of once-a-week outpatient
      rehabilitation followed by home program with tele-monitoring in patients with
      complex cyanotic congenital heart disease. DESIGN: Prospective nonrandomized
      study. METHOD: Patients who have been diagnosed either Eisenmenger's syndrome or
      inoperable complex cyanotic heart disease and able to attend 12-week cardiac
      rehabilitation program were included. Training with treadmill walking and
      bicycling under supervision at cardiac rehabilitation unit once-a-week in the
      first 6 weeks followed by home-based exercise program (bicycle and walking) with
      a target at 40%-70% of maximum heart rate (HRmax) at pretraining peak exercise
      for another 6 weeks was performed in the intervention group. Video and telephone
      calls were scheduled for evaluation of compliance and complication. Data from
      cardiopulmonary exercise testing (CPET) on cycle ergometry including peak oxygen
      consumption (peakVO2 ), oxygen pulse (O2 pulse), ventilatory equivalent for
      carbon dioxide (VE/CO2 at anaerobic threshold), constant work-rate endurance time
      (CWRET) at 75% of peak VO2 , and 6-minute walk distance (6MWD) were compared
      between baseline and after training by paired t test. RESULT: Of the 400 patients
      in our adult congenital heart disease clinic, 60 patients met the inclusion
      criteria. Eleven patients who could follow program regularly were assigned home
      program. There was a statistically significant improvement of CWRET, O2 pulse,
      and 6MWD after finishing the program (P = .003, .039, and .001, respectively).
      The mean difference of 6MWD change in the home-program group was significantly
      higher than in the control group (69.3 +/- 47.9 meters vs. 4.1 +/- 43.4 meters, P
      = .003). No serious adverse outcomes were reported during home training.
      CONCLUSION: Once-a-week outpatient hospital-based exercise program followed by
      supervised home-based exercise program showed a significant benefit in
      improvement of exercise capacity in adults with complex cyanotic congenital heart
      disease without serious adverse outcomes.

PMID- 30216681
TI  - In vitro functional evaluation of isolaureline, dicentrine and glaucine
      enantiomers at 5-HT2 and alpha1 receptors.
AB  - Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT2 and alpha1
      adrenergic receptors have potential for the treatment of central nervous system
      disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine
      enantiomers were synthesized, and their in vitro functional activities at human 5
      HT2 and adrenergic alpha1 receptor subtypes were evaluated. The enantiomers of
      isolaureline and dicentrine acted as antagonists at 5-HT2 and alpha1 receptors
      with (R)-isolaureline showing the greatest potency (pKb  = 8.14 at the 5-HT2C
      receptor). Both (R)- and (S)-glaucine also antagonized alpha1 receptors, but they
      behaved very differently to the other compounds at 5-HT2 receptors: (S)-glaucine
      acted as a partial agonist at all three 5-HT2 receptor subtypes, whereas (R)
      glaucine appeared to act as a positive allosteric modulator at the 5-HT2A
      receptor.

PMID- 30216682
TI  - Vacuolar sucrose cleavage prevents limitation of cytosolic carbohydrate
      metabolism and stabilizes photosynthesis under abiotic stress.
AB  - Stabilization of central carbohydrate metabolism plays a key role in plant stress
      response. Carbohydrates are substrate for numerous metabolic and stress
      responsive reactions and have been shown to be involved in diverse signalling
      processes on a whole-plant level. Regulation of enzymatic sucrose synthesis and
      degradation is well-known to be central to many stress-related processes as it
      significantly impacts stress tolerance. Leaf sucrose metabolism involves sucrose
      cleavage by invertases and ATP-consuming resynthesis catalysed by hexokinase and
      sucrose phosphate synthase. These reactions establish a metabolic cycle. To study
      the physiological role of sucrose cycling, a kinetic model was developed to
      simulate dynamics of subcellular sugar concentrations in Arabidopsis thaliana
      under combined cold and high-light stress. Model simulation revealed that
      subcellular reprogramming of invertase-driven sucrose cleavage varies
      substantially between natural accessions of Arabidopsis which differ in their
      cold tolerance levels. A stress-induced shift of sucrose cleavage from the
      cytosol into the vacuole could only be observed for the tolerant accession while
      the susceptible accession increased the cytosolic proportion of sucrose cleavage.
      Under stress, reduction in vacuolar invertase activity significantly affected
      maximum quantum yield of photosystem II and CO2 assimilation rates. While wild
      type plants circumvented a limitation of sucrose cleavage by increasing vacuolar
      invertase activity, mutant plants were not able to compensate their deficiency of
      vacuolar by cytosolic activity. Consequently, the capacity for cytosolic hexose
      generation was lower than for enzymatic hexose phosphorylation suggesting a role
      of vacuolar invertase activity in preventing a limitation in cytosolic hexose
      metabolism under stress. ENZYMES: Invertase, EC 3.2.1.26; Hexokinase, EC 2.7.1.1.

PMID- 30216683
TI  - The association of HBG2, BCL11A, and HMIP polymorphisms with fetal hemoglobin and
      clinical phenotype in Iraqi Kurds with sickle cell disease.
AB  - INTRODUCTION: Fetal hemoglobin (HbF) is the major modifier for sickle cell
      disease (SCD) severity. HbF is modulated mainly by three major quantitative trait
      loci (QTL) on chromosomes 2, 6, and 11. METHODS: Five SNPs in the three QTLs
      (HBG2, rs7482144; BCL11A, rs1427407 and rs10189857; and HBS1L-MYB intergenic
      region, rs28384513 and rs9399137) were investigated by multiplex PCR and reverse
      hybridization, and their roles in HbF and clinical phenotype variability in Iraqi
      Kurds with SCD were assessed. RESULTS: HBG2 rs7482144 with minor allele frequency
      (MAF) of 0.133 was the most significant contributor to HbF variability,
      contributing 18.1%, followed by rs1427407 (MAF of 0.266) and rs9399137 (MAF of
      0.137) at 14.3% and 8.8%, respectively. The other two SNPs were not significant
      contributors. Furthermore, when the cumulative numbers of minor alleles in the
      three contributing SNPs were assessed, HbF% and hemoglobin concentration
      increased with increasing number of minor alleles (P < 0.0005 and 0.001,
      respectively), while serum lactic dehydrogenase, reticulocytes, leukocytes,
      transfusion, and pain frequencies decreased (P = 0.003, 0.004, <0.0005, <0.0005,
      and 0.017, respectively). CONCLUSIONS: It was demonstrated that SNPs in all three
      major HbF QTLs contribute significantly to HbF and clinical variability in Iraqi
      Kurds with SCD and that the cumulative number of minor alleles at contributing
      SNPs may serve as a better predictor of such variability in this population.

PMID- 30216684
TI  - Carcinocythemia: A rare entity becoming more common? A 3-year, single institution
      series of seven cases and literature review.
AB  - INTRODUCTION: Carcinocythemia is a rare phenomenon defined as morphologically
      identifiable, circulating tumor cells in the peripheral blood. No modern case
      series of carcinocythemia exists in the literature. METHODS: Blood smears from
      carcinocythemia patients were reviewed and associated clinicopathologic findings
      described and compared to the literature. When available, bone marrows were
      examined. RESULTS: We identified 7 carcinocythemia cases over 3 years at our
      institution in 5 females and 2 males with a median age of 57 and compare them to
      26 case reports in the literature (19 females, 10 males; median age 57). The
      primary neoplasms were carcinomas of breast (3 cases), lung, non-small cell (2
      cases), prostate (1), and 1 case of unknown primary. Circulating tumor cells were
      associated with fragmentation hemolysis (2 cases), asplenic RBC changes (3
      cases), and myeloid antigen expression by flow cytometry (2 cases) and were most
      commonly found at the feathered edge of the slide (6 cases) as single cells or in
      clusters. CONCLUSIONS: This represents the largest series of carcinocythemia
      reported. The identification of 7 cases at one institution over a 3-year period
      suggests carcinocythemia may becoming more common. Raising awareness of this
      entity and its associated clinicopathologic findings may help avoid diagnostic
      pitfalls in blood smear examinations and may guide timely clinical management.

PMID- 30216685
TI  - Secochiliolide ester derivatives: Preparation and evaluation of their
      antitrypanosomal and antimalarial efficacy.
AB  - In the present study, a series of new esters of secochiliolide acid (SA), a
      diterpene isolated from Nardophyllum bryoides, were synthesized in good yield.
      All compounds were evaluated for their in vitro antiparasitic properties (on
      Plasmodium falciparum and Trypanosoma brucei brucei) and cytotoxicity (on WI38,
      normal mammalian cells). They displayed moderate antitrypanosomal activity with
      IC50 values between 2.55 and 18.14 MUm, with selectivity indices >10, and low
      antiplasmodial effects with IC50  > 29 MUm. The only exception was the n-hexyl
      ester of SA, which showed a strong and selective antiplasmodial activity (IC50  =
      1.99 MUm and selectivity index = 117.0). The in vivo antimalarial efficacy of
      this compound was then assessed according to the 4-day suppressive test of Peters
      in mice. An intraperitoneal treatment at 50 mg kg-1  day-1 induced a slight
      parasitaemia reduction by 56% which was statistically significant on day 4 post
      infection and an increase in the survival time.

PMID- 30216686
TI  - Technetium-99m radiolabeling and biological study of epirubicin for in vivo
      imaging of multi-drug-resistant Staphylococcus aureus infections via single
      photon emission computed tomography.
AB  - The development of functional imaging is a promising strategy for diagnosis and
      treatment of infectious and cancerous diseases. In this study, epirubicin was
      developed as a [99m Tc]-labeled radiopharmaceutical for the imaging of multi-drug
      resistant Staphylococcus aureus infections. The labeling was carried out using
      sodium pertechnetate (Na99m TcO4 ; ~370 MBq). The other parameters such as amount
      of ligand, reducing agent (SnCl2 .2H2 O), and pH were optimized. The highest
      labeling yield >=96.98% was achieved when 0.3 mg epirubicin, 13 MUg SnCl2 .2H2 O,
      and ~370 MBq Na99m TcO4 were incubated at pH 7 for 15 min in the presence of
      ascorbic acid at room temperature. Radiochemical purity, stability, charge, and
      glomerular filtration rate were studied to evaluate the biological compatibility
      for in vivo administration. Biodistribution investigations showed radiotracer
      uptake (13.89 +/- 1.56% ID/gm organ) by liver and 7.79 +/- 0.38% ID/gm organ by
      kidneys at 30 min post-injection which promisingly wash out at 24 hr post
      injection. Scintigraphy study showed selective uptake in S. aureus-infected
      tissues in contrast to turpentine oil-induced inflamed tissues. Target-to-non
      target ratio (6.7 +/- 0.05) was calculated at 1 hr post-injection using SPECT
      gamma camera. The results of this study reveal that the [99m Tc]-epirubicin can
      be a choice of imaging and monitoring the treatment process of multi-drug
      resistant S. aureus bacterial infections.

PMID- 30216687
TI  - In MALDI-Mass Spectrometry Imaging on Formalin-Fixed Paraffin-Embedded Tissue
      Specimen Section Thickness Significantly Influences m/z Peak Intensity.
AB  - BACKGROUND: In matrix-assisted laser desorption/ionization-mass spectrometry
      imaging (MALDI-MSI) standardized sample preparation is important to obtain
      reliable results. Herein, the impact of section thickness in formalin-fixed
      paraffin embedded (FFPE) tissue microarrays (TMA) on spectral intensities is
      investigated. PATIENTS AND METHODS: TMAs consisting of ten different tissues
      represented by duplicates of ten patients (n = 200 cores) are cut at 1, 3, and 5
      MUm. MSI analysis is performed and mean intensities of all evaluable cores are
      extracted. Measurements are merged and mean m/z intensities are compared.
      RESULTS: Visual inspection of spectral intensities between 1, 3, and 5 MUm
      reveals generally higher intensities in thinner tissue sections. Specifically,
      higher intensities are observed in the vast majority of peaks (98.6%, p < 0.01)
      in 1 MUm compared with 5 MUm sections. Note that 28.4% and 2.1% of m/z values
      exhibit a at least two- and threefold intensity difference (p < 0.01) in 1 MUm
      compared to 5 MUm sections, respectively. CONCLUSION: A section thickness of 1
      MUm results in higher spectral intensities compared with 5 MUm. The results
      highlight the importance of standardized protocols in light of recent efforts to
      identify clinically relevant biomarkers using MSI. The use of TMAs for
      comparative analysis seems advantageous, as section thickness displays less
      variability.

PMID- 30216688
TI  - The use of immersive virtual reality for pain control during periodontal scaling
      and root planing procedures in dental hygiene clinic.
AB  - OBJECTIVE: To identify the effect of immersive virtual reality (VR) on pain
      perception during scaling and root planing procedures (SRP) in dental hygiene
      clinic. METHODS: Participants were recruited based on inclusion and exclusion
      criteria. Within-subject/split-mouth design was used in this study. The
      participants received a full mouth SRP. The participants were divided into two
      treatment conditions: (a) without VR condition or (b) with VR condition. Blood
      pressure (BP) and pulse rate (PR) were measured. Level of pain was measured by
      the Visual Analog Scale (VAS). Participants gave ratings using 0-10 scales with
      cut points on the scale indicating that (0) none, (1-3) mild, (4-6) moderate or
      (7-10) severe. Participants were also asked three questions to assess presence,
      realism and nausea. The immersive virtual environment used for this study was
      nonviolent and inoffensive. RESULTS: Data were analysed using SPSS(r) software.
      Fifty subjects with a mean age of 36 years completed the study. The Wilcoxon
      signed-rank test revealed that VAS scores were significantly (P = < 0.05) lower
      during VR compared without VR condition. Paired t test revealed that on average,
      participants experienced significantly lower systolic Bp after using VR (M =
      113.72, SE = 2.16) than systolic Bp after treatment without VR However, Bp
      (diastolic) and PR showed no difference. 84% of the participants felt like they
      went inside the virtual world, 82% felt that the virtual objects seem real to
      them, and 94% did not feel nausea. 98% of the participants preferred using VR
      during SRP. CONCLUSIONS: The results of this study indicate that the immersive VR
      has the potential in becoming a future method for pain control during scaling and
      root planing procedures.

PMID- 30216689
TI  - Exercise testing and spirometry as predictors of mortality in congenital heart
      disease: Contrasting Fontan physiology with repaired tetralogy of Fallot.
AB  - OBJECTIVE: Risk prediction using cardiopulmonary exercise testing (CPET) in
      complex congenital heart disease tends to either focus on single diagnoses or
      complete cohorts. We aimed to evaluate patients with two distinct anatomies cared
      for at a single institution over the same time period to determine CPET variables
      associated with mortality. DESIGN: All Fontan and tetralogy of Fallot (TOF)
      subjects with CPET between November 1, 2002 and December 31, 2014 and
      subsequently died were identified (cases). Cases were matched 1:3 to controls
      with similar age, underlying anatomy and timing of exercise test. RESULTS: Of the
      42 cases, 27 had a Fontan circulation and 15 with TOF. All Fontan patients had a
      low peak VO2 but there was no significant difference between cases and controls
      (52.5 +/- 14.7 v. 57.4% +/- 13.5% predicted, P = .11). Spirometry values were
      significantly lower in Fontan cases than controls (eg, FVC 67.4 +/- 19.1 v 77.6%
      +/- 14.9% predicted, P = .007). Spirometry values were also lower in TOF cases
      than controls (% predicted FVC 62.8 +/- 16.7 v 75 +/- 14, P = .006). In contrast
      to the Fontan analysis, both %peak predicted VO2 and VE/VCO2 slope were worse in
      TOF cases than controls (50.1 +/- 13.5 v. 68.5% +/- 15.0% predicted VO2 , P =
      .0004; 33.9 +/- 12.9 v 26.6 +/- 4.4, P = .002). Multivariable analysis also
      identified different predictors of mortality among the anatomic subgroups.
      Spirometric data (FVC) correlated most strongly with mortality in Fontan patients
      while the VE/VCO2 slope was most associated with outcome in TOF patients.
      CONCLUSIONS: Variables most predictive of mortality in Fontan and TOF patients
      diverge but spirometry was abnormal and associated with mortality in both groups.
      When compared with age-matched controls, reduced FEV1 and FVC correlated most
      strongly with mortality in Fontan patients while VE/VCO2 slope correlated with
      mortality for TOF patients. These findings further support the importance of lung
      health in patients with complex congenital heart disease.

PMID- 30216690
TI  - Recent Developments in Solid-Phase Strategies towards Synthetic, Sequence-Defined
      Macromolecules.
AB  - Sequence-control in synthetic polymers is an important contemporary research area
      because it provides the opportunity to create completely novel materials for
      structure-function studies. This is especially relevant for biomimetic polymers,
      bioactive and information security materials. The level of control is strongly
      dependent and inherent upon the polymerization technique utilized. Today, the
      most established method yielding monodispersity and monomer sequence-definition
      is solid-phase synthesis. This Focus Review highlights recent advances in solid
      phase strategies to access synthetic, sequence-defined macromolecules.
      Alternatives strategies towards sequence-defined macromolecules are also briefly
      summarized.

PMID- 30216691
TI  - Cinnamic acids derived compounds with antileishmanial activity target Leishmania
      amazonensis arginase.
AB  - This study describes the activity of five natural hydroxycinnamic acids and
      derived compound: caffeic (1), rosmarinic (2), chlorogenic (3), and
      cryptochlorogenic (4), acids and isoverbascoside (5). All compounds inhibited
      Leishmania amazonensis arginase with IC50 -in range of 1.5-11 MUM. Compounds 2
      and 5 also showed activity against promastigotes of L. amazonensis with IC50  =
      61 (28-133) MUM and IC50  = 14 (9-24) MUM, respectively. Further computational
      studies applying molecular docking simulations were performed on the competitive
      inhibitors to gain insight into the molecular basis for arginase inhibition and
      could be exploited to the development of new antileishmanials drug targeting
      parasite arginase.

PMID- 30216692
TI  - Tunable Fluorescence from a Responsive Hyperbranched Polymer with Spatially
      Arranged Fluorophore Arrays.
AB  - In the present study, a water-soluble hyperbranched polymer platform that
      contained a Forster resonance energy transfer (FRET) array and exhibited varied
      fluorescence in response to solvent, light, and CN- anion stimuli was
      constructed. The use of chain-growth copper-catalyzed azide-alkyne cycloaddition
      polymerization (CuAACP) enabled accurate control of the ratio and distance of
      three incorporated fluorophores, coumarin (Cou), nitrobenzoxadiazole (NBD), and
      photoswitchable spiropyran (SP), that could be reversibly transformed into the
      red-emitting merocyanine (MC) state. Within the FRET system, the energy flow from
      Cou to MC was significantly enhanced by the introduction of NBD as a central
      fluorophore relay. Moreover, the energy-transfer efficiency was increased by
      changing the solvent from tetrahydrofuran to more polar water; this was
      accompanied by a clear color change and fluorescence behavior. These correlations
      of polymer composition and solvent polarity to the FRET efficiency were finally
      applied to the effective detection of CN- anion; thus demonstrating a function of
      this polymer as a CN- sensor.

PMID- 30216694
TI  - Bad company: Microenvironmentally mediated resistance to targeted therapy in
      melanoma.
AB  - This review will focus on the role of the tumor microenvironment (TME) in the
      development of drug resistance in melanoma. Resistance to mitogen-activated
      protein kinase inhibitors (MAPKi) in melanoma is observed months after treatment,
      a phenomenon that is often attributed to the incredible plasticity of melanoma
      cells but may also depend on the TME. The TME is unique in its cellular
      composition-it contains fibroblasts, immune cells, endothelial cells, adipocytes,
      and among others. In addition, the TME provides "non-homeostatic" levels of
      oxygen, nutrients (hypoxia and metabolic stress), and extracellular matrix
      proteins, creating a pro-tumorigenic niche that drives resistance to MAPKi
      treatment. In this review, we will focus on how changes in the tumor
      microenvironment regulate MAPKi resistance.

PMID- 30216695
TI  - A previously unrecognized 22q13.2 microdeletion syndrome that encompasses TCF20
      and TNFRSF13C.
AB  - Phelan-McDermid syndrome (PMS, OMIM 606232) is a heterozygous contiguous gene
      microdeletion syndrome occurring at the distal region of chromosome 22q13. This
      deletion encompasses the SHANK3 gene at 22q13.33, which is thought to be the
      critical gene for the neurodevelopmental features seen in this syndrome. PMS is
      typically characterized by intellectual disability, autism spectrum disorder,
      absent to severely delayed speech, neonatal hypotonia, and dysmorphic features.
      Two patients presenting with classic clinical features of PMS have been reported
      to have interstitial microdeletions in the 22q13.2 region that map proximal to
      the SHANK3 gene (0.54 and 0.72 Mb, respectively). Here, we describe a 13-month
      old girl with a de novo 1.16 Mb interstitial deletion in the 22q13.2 region who
      presented with global developmental delay, subtle dysmorphic features, and
      immunodeficiency. This deletion overlaps with the two previously published cases
      and five cases from the DECIPHER database. All eight patients share features
      common to patients with PMS including developmental delay and language delay,
      which suggests that this represents a previously unrecognized microdeletion
      syndrome in the 22q13.2 region. Our patient's deletion encompasses the TCF20 and
      TNFRSF13C genes, which are thought to play causative roles in the patient's
      neurodevelopmental and immunological features, respectively.

PMID- 30216693
TI  - Improvement of Duchenne muscular dystrophy phenotype following obestatin
      treatment.
AB  - BACKGROUND: This study was performed to test the therapeutic potential of
      obestatin, an autocrine anabolic factor regulating skeletal muscle repair, to
      ameliorate the Duchenne muscular dystrophy (DMD) phenotype. METHODS AND RESULTS:
      Using a multidisciplinary approach, we characterized the ageing-related
      preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4-,
      8-, and 18-week-old mdx mice (n = 3/group) and established the effects of
      obestatin administration at this level in 8-week-old mdx mice (n = 5/group). The
      findings were extended to in vitro effects on human immortalized DMD myotubes. An
      analysis of TAs revealed an age-related loss of preproghrelin expression, as
      precursor of obestatin, in mdx mice. Administration of obestatin resulted in a
      significant increase in tetanic specific force (33.0% +/- 1.5%, P < 0.05),
      compared with control mdx mice. Obestatin-treated TAs were characterized by
      reduction of fibres with centrally located nuclei (10.0% +/- 1.2%, P < 0.05)
      together with an increase in the number of type I fibres (25.2% +/- 1.7%, P <
      0.05) associated to histone deacetylases/myocyte enhancer factor-2 and peroxisome
      proliferator-activated receptor-gamma coactivator 1alpha axis, and down
      regulation of ubiquitin E3-ligases by inactivation of FoxO1/4, indexes of muscle
      atrophy. Obestatin reduced the level of contractile damage and tissue fibrosis.
      These observations correlated with decline in serum creatine kinase (58.8 +/-
      15.2, P < 0.05). Obestatin led to stabilization of the sarcolemma by up
      regulation of utrophin, alpha-syntrophin, beta-dystroglycan, and alpha7beta1
      integrin proteins. These pathways were also operative in human DMD myotubes.
      CONCLUSIONS: These results highlight the potential of obestatin as a peptide
      therapeutic for preserving muscle integrity in DMD, thus allowing a better
      efficiency of gene or cell therapy in a combined therapeutic approach.

PMID- 30216696
TI  - Digital PCR After MALDI-Mass Spectrometry Imaging to Combine Proteomic Mapping
      and Identification of Activating Mutations in Pulmonary Adenocarcinoma.
AB  - PURPOSE: Matrix assisted laser desorption/ionization time-of-flight mass
      spectrometry imaging (MALDI-MSI) is a powerful tool to analyze the spatial
      distribution of peptides in tissues. Digital PCR (dPCR) is a method to reliably
      detect genetic mutations. Biopsy material is often limited due to minimally
      invasive techniques, but information on diagnosis, prognosis, and prediction is
      required for subsequent clinical decision making. Thus, saving tissue material
      during diagnostic workup is highly warranted for best patient care. The
      possibility to combine proteomic analysis by MALDI-MSI and mutational analysis by
      dPCR from the same tissue section is evaluated. EXPERIMENTAL DESIGN: Ten 0.5 *
      0.5 cm formalin-fixed paraffin embedded tissue samples of pulmonary
      adenocarcinomas with known EGFR or KRAS mutations are analyzed by MALDI-MSI.
      Subsequently, DNA is extracted from the analyzed tissue material and tested for
      the respective driver mutation by dPCR. RESULTS: Detection of driver gene
      mutations after MALDI MSI analysis is successful in all analyzed samples.
      Determined mutant allele frequencies are in good agreement with values assessed
      from untreated serial tissue sections with a mean absolute deviation of 0.16.
      CONCLUSION AND CLINICAL RELEVANCE: It has been demonstrated that MALDI-MSI can be
      combined with genetic analysis, like dPCR. Workflows enabling the subsequent
      analysis of proteomic and genetic markers are particularly promising for the
      analysis of limited sample material such as biopsy specimen.

PMID- 30216697
TI  - Contribution of commercial infant products and fortified staple foods to nutrient
      intake at ages 6, 12, and 18 months in a cohort of children from a low socio
      economic community in South Africa.
AB  - Fortification of two staple foods, maize meal and wheat flour (bread), is
      mandatory, and commercial infant products are widely available in South Africa.
      Using a 24-hr recall, we determined the contribution of these foods towards
      nutrient intakes at ages 6 (n = 715), 12 (n = 446), and 18 (n = 213) months in a
      cohort of children in a peri-urban community, North West province. On the day of
      recall, commercial infant products were consumed by 83% of children at 6 months,
      46% at 12 months, and 15% at 18 months; fortified staples were consumed by 23%,
      81%, and 96%, respectively. For consumers thereof, commercial infant products
      contributed 33% energy and 94% iron intakes at 6 months and 27% energy and 56%
      iron intakes at 12 months; nutrient densities of the complementary diet was
      higher than for nonconsumers for most micronutrients. For consumers of fortified
      staples, energy contribution thereof was 11% at 6 months versus 29% at 18 months;
      at 18 months, fortified staples contributed >30% of iron, zinc, vitamin A,
      thiamine, niacin, vitamin B6, and folate; at 12 months, nutrient densities of the
      complementary diet were higher for zinc, folate, and vitamin B6 but lower for
      calcium, iron, vitamin A, niacin, and vitamin C than nonconsumers. At ages 12 and
      18 months, ~75% of children had low calcium intakes. At 12 months, 51.4% of
      consumers versus 25.0% (P = 0.005) of nonconsumers of fortified staples had
      adequate intakes (>EAR) for all eight fortificant nutrients. However, despite
      fortification, nutrient gaps remain.

PMID- 30216698
TI  - Environmental influences on RNA processing: Biochemical, molecular and genetic
      regulators of cellular response.
AB  - RNA processing has emerged as a key mechanistic step in the regulation of the
      cellular response to environmental perturbation. Recent work has uncovered
      extensive remodeling of transcriptome composition upon environmental perturbation
      and linked the impacts of this molecular plasticity to health and disease
      outcomes. These isoform changes and their underlying mechanisms are varied
      involving alternative sites of transcription initiation, alternative splicing,
      and alternative cleavage at the 3' end of the mRNA. The mechanisms and
      consequences of differential RNA processing have been characterized across a
      range of common environmental insults, including chemical stimuli, immune
      stimuli, heat stress, and cancer pathogenesis. In each case, there are
      perturbation-specific contributions of local (cis) regulatory elements or global
      (trans) factors and downstream consequences. Overall, it is clear that choices in
      isoform usage involve a balance between the usage of specific genetic elements
      (i.e., splice sites, polyadenylation sites) and the timing at which certain
      decisions are made (i.e., transcription elongation rate). Fine-tuned cellular
      responses to environmental perturbation are often dependent on the genetic makeup
      of the cell. Genetic analyses of interindividual variation in splicing have
      identified genetic effects on splicing that contribute to variation in complex
      traits. Finally, the increase in the number of tissue types and environmental
      conditions analyzed for RNA processing is paralleled by the need to develop
      appropriate analytical tools. The combination of large datasets, novel methods
      and conditions explored promises to provide a much greater understanding of the
      role of RNA processing response in human phenotypic variation. This article is
      categorized under: RNA Processing > RNA Editing and Modification RNA Evolution
      and Genomics > Computational Analyses of RNA RNA Processing > Splicing Mechanisms
      RNA Processing > Splicing Regulation/Alternative Splicing.

PMID- 30216700
TI  - HToPred: A Tool for Human Topoisomerase II Inhibitor Prediction.
AB  - The enzyme human topoisomerase IIalpha (hTopoIIalpha) is an important anticancer
      drug target. Due to the availability of multiple inhibitor-binding sites in this
      enzyme, the anti-hTopoII agents possess high chemical diversity. Chemoinformatics
      methods can be used to identify lead compounds from large databases for hTopoII
      inhibitory activity and classify them. In this work, we report the use of machine
      learning methods to develop classification models for the identification of
      possible anti-hTopoIIalpha agents and to classify them as catalytic inhibitors
      vs. poisons. Initially, an extensive dataset of small molecules which are
      reported to be evaluated towards hTopoIIalpha inhibition was collected from
      ChEMBL database and literature. Using this dataset, predictive models for
      classifying small molecules into hTopoIIalpha inhibitors and non-inhibitors were
      developed. Additionally, the model development was taken up for the prediction of
      the type of hTopoIIalpha inactivation. Several molecular fingerprints and
      physicochemical descriptors of the molecules in the dataset were calculated using
      the chemoinformatics tool RDKit. Various classifiers were evaluated to establish
      suitable protocol. Further, ensemble models were developed by bagging of
      homogenous classifier and selective fusion of heterogeneous classifiers. The
      models were thoroughly validated with 5-fold cross validation and external
      validation. The best performing models were incorporated into a tool christened
      as Human Topoisomerase IIalpha Inhibitor Prediction (HToPred,
      http://14.139.57.41/HToPred). A molecular docking based validation for the
      successful application of HToPred in predicting the mode of enzyme inhibition was
      performed, which further established the acceptability of this tool. This tool
      can serve as an important platform to prescreen compounds for anti-hTopoIIalpha
      potential.

PMID- 30216701
TI  - Herd-level prevalence of Salmonella Dublin among New York dairy farms based on
      antibody testing of bulk tank milk.
AB  - Salmonella Dublin is an important cause of salmonellosis among dairy cattle and
      poses a considerable threat to public health. This serotype is increasingly being
      identified among bovine Salmonella isolates from clinical samples in the north
      eastern United States, and these isolates are generally multidrug resistant. Our
      objective was to estimate the herd-level prevalence of Salmonella Dublin among
      dairy cattle herds throughout New York. Bulk tank milk samples from nearly all
      commercial dairy herds in New York were collected from milk quality testing
      laboratories during the first half of 2013. Antibody testing of bulk tank milk
      was performed using a Salmonella Dublin ELISA kit. Samples representing 4,896
      commercial dairies were collected, and antibodies against Salmonella Dublin were
      detected in 46 herds (0.9%; 95% CI, 0.7%-1.3%). Given the herd-level sensitivity
      of ELISA testing for Salmonella Dublin in bulk tank milk at a single timepoint,
      this approach presumably underestimated the true prevalence. Some Salmonella
      Dublin-positive herds had both positive and negative bulk tanks at the same
      sampling time, indicating that herds with multiple tanks should test all of them
      when using this ELISA. Further research is needed to better understand the
      epidemiologic features of Salmonella Dublin in the north-eastern United States,
      including risk factors for introduction into dairy herds and principal
      transmission pathways.

PMID- 30216699
TI  - Jack of many trades: Multifaceted role of neuropilins in pancreatic cancer.
AB  - Neuropilins (NRPs) have been described as receptors for class 3 semaphorins and
      coreceptors for a plethora of ligands, such as members of the vascular
      endothelial growth factor (VEGF) family of angiogenic cytokines and transforming
      growth factor (TGF). Initial studies using genetic models have indicated that
      neuropilin-1 (NRP-1) is essential for axonal guidance during neuronal and
      cardiovascular development, regulated via semaphorins and VEGF, respectively,
      whereas the other homolog of neuropilin, NRP-2, has been shown to play a more
      specific role in neuronal patterning and lymphangiogenesis. Pancreatic ductal
      adenocarcinoma (PDAC) remains a significant cause of cancer mortality with the
      lowest five-year survival rate compared to other types of cancer. Recent findings
      have indicated that NRPs are abundantly expressed in pancreatic cancer cell lines
      and pancreatic tumor tissues, where they mediate several essential cancer
      initiating and cancer-promoting functional responses through their unique ability
      to bind multiple ligands. Specifically, NRPs have been implicated in numerous
      biological processes such as cancer cell proliferation, survival, invasion, and
      tumor growth. More recently, several other protumorigenic roles mediated by NRPs
      have emerged, advocating NRPs as ideal therapeutic targets against PDAC.

PMID- 30216703
TI  - Pro-inflammatory role of transient receptor potential canonical channel 6 in the
      pathogenesis of chronic rhinosinusitis with nasal polyps.
AB  - BACKGROUND: The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP)
      has not been fully elucidated. This study sought to explore the role and
      mechanism of transient receptor potential canonical channel 6 (TRPC6) in the
      pathogenesis of CRSwNP. METHODS: Immunohistochemistry (IHC) was employed to
      evaluate TRPC6 immunolabeling. Real-time polymerase chain reaction (PCR) was
      conducted to assay TRPC6, stromal interaction molecule 1 (STIM1), and calcium
      release-activated calcium channel protein 1 (Orai1) messenger RNA (mRNA) levels
      in 70 patients with CRSwNP, including eosinophilic CRSwNP (ECRSwNP) or non
      eosinophilic CRSwNP (nECRSwNP), and 28 control subjects. The concentrations of
      inflammatory mediators, including interleukin (IL)-1beta, IL-5, and IL-25, were
      assayed by enzyme-linked immunosorbent assay (ELISA). In experiments on human
      nasal epithelial cell (HNEC) culture and stimulation, the mean fluorescence
      intensity (MFI) of intracellular Ca2+ was assayed by flow cytometry. Western
      blotting, real-time PCR, and ELISA were also conducted to assess the effects and
      mechanisms of TRPC6 activator 1-oleoyl-2-acetyl-glycerol (OAG) and TRPC6
      inhibitor 1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl) propoxy]ethyl-1H
      imidazole (SKF-96365) on HNECs. RESULTS: Upregulation of TRPC6, STIM1, and Orai1
      levels was found in CRSwNP patients, particularly in those with ECRSwNP. TRPC6
      positive cells correlated positively with the numbers of eosinophils and
      neutrophils, respectively. Moreover, TRPC6 mRNA was positively correlated with
      STIM1 and Orai1 mRNA levels. The concentrations of inflammatory mediators,
      including IL-1beta, IL-5, and IL-25, were elevated in CRSwNP, especially in
      ECRSwNP. In cultured HNECs, TRPC6, STIM1, Orai1, Ca2+ MFI levels, and
      inflammatory mediators were upregulated by lipopolysaccharide (LPS) and OAG but
      were inhibited by SKF-96365. CONCLUSION: TRPC6 plays a pro-inflammatory role in
      the pathogenesis of CRSwNP via regulating Ca2+ flow.

PMID- 30216702
TI  - Detectors assessment for stereotactic radiosurgery with cones.
AB  - The purpose of this work is to assess eight detectors performance for output
      factor (OF), percent depth dose (PDD), and beam profiles in a 6-MV Clinac
      stereotactic radiosurgery mode for cone irradiation using Monte Carlo simulation
      as reference. Cones with diameters comprised between 30 and 4 mm have been
      studied. The evaluated detectors were ionization chambers: pinpoint and pinpoint
      3D, diodes: SRS, P and E, Edge, MicroDiamond and EBT3 radiochromic films. The
      results showed that pinpoints underestimate OF up to -2.3% for cone diameters
      >=10 mm and down to -12% for smaller cones. Both nonshielded (SRS and E) and
      shielded diodes (P and Edge) overestimate the OF respectively up to 3.3% and 5.2%
      for cone diameters >=10 mm and in both cases more than 7% for smaller cones.
      MicroDiamond slightly overestimates the OF, 3.7% for all the cones and EBT3 film
      is the closest to Monte Carlo with maximum difference of +/-1% whatever the cone
      size is. For the profiles and the PDD, particularly for the small cones, the size
      of the detector predominates. All diodes and EBT3 agree with the simulation
      within +/-0.2 mm for beam profiles determination. For PDD curve all the active
      detectors response agree with simulation up to 1% for all the cones. EBT3 is the
      more accurate detector for beam profiles and OF determinations of stereotactic
      cones but it is restrictive to use. Due to respectively inappropriate size of the
      sensitive volume and composition, pinpoints and diodes do not seem appropriate
      without OF corrective factors below 10 mm diameter cone. MicroDiamond appears to
      be the best detector for OF determination regardless all cones. For off-axis
      measurements, the size of the detector predominates and for PDD all detectors
      give promising results.

PMID- 30216704
TI  - An optimized procedure to develop a 3-dimensional microfluidic hydrogel with
      parallel transport networks.
AB  - The development of microfluidic hydrogels is an attractive method to generate
      continuous perfusion, induce vascularization, increase solute delivery, and
      ultimately improve cell viability. However, the transport processes in many in
      vitro studies still have not been realized completely. To address this problem,
      we have developed a microchanneled hydrogel with different collagen type I
      concentrations of 1, 2, and 3 wt% and assessed its physical properties and
      obtained diffusion coefficient of nutrient within the hydrogel. It is well known
      that microchannel geometry has critical role in maintaining stable perfusion
      rate. Therefore, in this study, a computational modeling was applied to simulate
      the 3D microfluidic hydrogel and study the effect of geometric parameters such as
      microchannel diameters and their distance on the nutrient diffusion. The
      simulation results showed that the sample with 3 channels with a diameter of 300
      MUm has adequate diffusion rates and efficiency (56%). Moreover, this system
      provides easy control and continuous perfusion rate during 5 days of cell
      culturing. The simulation results were compared with experimental data, and a
      good correlation was observed for nutrient profiles and cell viability across the
      hydrogel.

PMID- 30216706
TI  - Moving slowly but surely toward more precise rhinologic care.

PMID- 30216705
TI  - International assessment of inter- and intrarater reliability of the
      International Frontal Sinus Anatomy Classification system.
AB  - BACKGROUND: Inconsistencies in the nomenclature of structures of the frontal
      sinus have impeded the development of a validated "reference standard"
      classification system that surgeons can reliably agree upon. The International
      Frontal Sinus Anatomy Classification (IFAC) system was developed as a consensus
      document, based on expert opinion, attempting to address this issue. The purposes
      of this study are to: establish the reliability of the IFAC as a tool for
      classifying cells in the frontal recess among an international group of
      rhinologists; and improve communication and teaching of frontal endoscopic sinus
      surgery (ESS). METHODS: Forty-two computed tomography (CT) scans, each with a
      marked frontal cell, were reviewed by 15 international fellowship-trained
      rhinologists. Each marked cell was classified into 1 of 7 categories described in
      the IFAC, on 2 occasions separated by 2 weeks. Inter- and intrarater reliability
      were evaluated using Light's kappa (kappa), the interclass correlation
      coefficient (ICC), and simple proportion of agreement. RESULTS: Interrater
      reliability showed pairwise kappa values ranging from 0.7248 to 1.0, with a mean
      of 0.9162 (SD, 0.0537). The ICC was 0.98. Intrarater reliability showed kappa
      values ranging from 0.8613 to 1.0, with a mean of 0.9407 (SD, 0.0376). The within
      rater ICC was 0.98. CONCLUSION: Among a diverse sample of rhinologists (raters),
      there was substantial to almost perfect agreement between raters, and among
      individual raters at different timepoints. The IFAC is a reliable tool for
      classification of cells in the frontal sinus. Further outcome studies are still
      needed to determine the validity of the IFAC.

PMID- 30216707
TI  - What clinical rotation factors have an impact on trainee success?
AB  - BACKGROUND: Educators and trainees both recognise that autonomy, the number of
      patient encounters and setting learning outcomes are all vital for a successful
      residency. This study examined whether these clinical rotation characteristics
      have an impact on trainee success in an orthotic and prosthetic clinical
      residency. METHODS: Two cohorts of resident trainees rated their rotation
      characteristics (autonomy, patient encounters and learning outcomes [1,
      significantly below expectations; 5, exceeds expectations]) and self-competency
      (77 items [1, not at all able; 5, very able]) at three points during an 18-month
      residency. Rotation performance (0-100, where 100 is the highest score) was
      ascertained with preceptor ratings and test scores. Means and correlations were
      derived. RESULTS: Data from 38 trainees were examined. The mean self-competency
      and rotation performance scores improved from time 1 to time 3 (from 4.14 +/-
      0.43 to 4.36 +/- 0.38 [p < 0.01]; from 90.74 +/- 5.15 to 92.62 +/- 4.55 [p <
      0.05]). Autonomy correlated with performance at time 1 (p < 0.05) only, and did
      not relate to self-competency at any point. Neither the number of patient
      encounters nor the presence of learning outcomes were associated with performance
      or self-competency at any point. CONCLUSIONS: These data show that over time our
      trainees become more competent, as rated by both themselves and their preceptors.
      These data do not suggest that the number of patient encounters and the presence
      of learning outcomes have an impact on trainee competence. Autonomy may play the
      largest role at the beginning of the residency as students make the transition to
      clinical practice.

PMID- 30216708
TI  - Omega-3 polyunsaturated fatty acids exert anti-oxidant effects through the
      nuclear factor (erythroid-derived 2)-related factor 2 pathway in immortalized
      mouse Schwann cells.
AB  - AIMS/INTRODUCTION: Recent studies advocate that omega-3 polyunsaturated fatty
      acids (omega-3 PUFAs) have direct anti-oxidative and anti-inflammatory effects in
      the vasculature; however, the role of omega-3 PUFAs in Schwann cells remains
      undetermined. MATERIALS AND METHODS: Immortalized mouse Schwann (IMS32) cells
      were incubated with the omega-3 PUFAs docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA). The messenger ribonucleic acid levels of several
      anti-oxidant enzymes (heme oxygenase-1 [Ho-1], nicotinamide adenine dinucleotide
      [phosphate] H quinone oxidoreductase 1, catalase, superoxide dismutase and
      glutathione peroxidase) were identified using real-time reverse transcription
      polymerase chain reaction. Ho-1 and nicotinamide adenine dinucleotide [phosphate]
      H quinone oxidoreductase 1 protein levels were evaluated using Western blotting.
      Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) of the nuclear
      fraction was also quantified using western blotting. Catalase activity and
      glutathione content were determined by colorimetric assay kits. Nrf2 promoter
      luciferase activity was evaluated by a dual luciferase assay system. RESULTS:
      Treatment with tert-butyl hydroperoxide decreased cell viability dose
      dependently. DHA or EPA pretreatment significantly alleviated tert-butyl
      hydroperoxide-induced cytotoxicity. DHA or EPA increased the messenger
      ribonucleic acid levels of Ho-1, nicotinamide adenine dinucleotide (phosphate) H
      quinone oxidoreductase 1 and catalase dose-dependently. Ho-1 protein level,
      catalase activity, Nrf2 promoter-luciferase activity and intracellular
      glutathione content were significantly increased by DHA and EPA. CONCLUSIONS:
      These findings show that DHA and EPA can induce Ho-1 and catalase through Nrf2,
      thus protecting Schwann cells against oxidative stress. omega-3 PUFAs appear to
      exert their neuroprotective effect by increasing defense mechanisms against
      oxidative stress in diabetic neuropathies.

PMID- 30216709
TI  - An environmentally friendly method for the enantioseparation and determination of
      benalaxyl in tobacco and soil by ultra-performance convergence chromatography
      with tandem mass spectrometry.
AB  - For the purpose of chiral separation and determination of benalaxyl enantiomers
      in tobacco and soil, we developed a rapid, green, and sensitive method using
      ultra-performance convergence chromatography with tandem mass spectrometry. The
      samples were extracted and purified by the quick, easy, cheap, effective, rugged,
      and safe method before injection. The baseline separation was obtained on a
      chiral column in 5 min with carbon dioxide and ethanol as mobile phase.
      Separation parameters were optimized for the best separation efficiency. Under
      optimal conditions, the recoveries of both enantiomers were 77.1-98.4% with
      relative standard deviations <5.0% at spiked level of 0.1, 2.0, and 5.0 mg/kg in
      two matrices. Good coefficients of determination were achieved over the
      concentration range of 10-250 ng/mL. The limit of detection and the limit of
      quantification for all enantiomers ranged from 0.43 to 0.72 MUg/kg and from 1.25
      to 2.15 MUg/kg, respectively. The results show that ultra-performance convergence
      chromatography with tandem mass spectrometry provides a reliable, green, and
      rapid method for the separation and determination of benalaxyl enantiomers in
      tobacco and soil. This method has important theoretical significance for studying
      the enantioselectivity and bioactivity of benalaxyl in the environment and in
      organisms.

PMID- 30216710
TI  - Use of a capillary specimen in the laboratory to verify a point-of-care
      international normalized ratio: Avoidance of a venipuncture in a pediatric
      setting.
AB  - INTRODUCTION: Point-of-care (POC) international normalized ratio (INR) values
      above an institutional cutoff are confirmed in the laboratory using a gold
      standard venous specimen. This can be problematic in a pediatric setting. METHOD:
      In this study, 449 consecutive POC INR results were compared to an INR performed
      in the laboratory on a capillary citrate specimen collected from the same finger
      stick. The results were statistically analyzed. RESULTS: The mean INR values from
      the CoaguChek XS and laboratory were 2.85 +/- 1.19 and 2.63 +/- 1.11,
      respectively. There was a good correlation between the methods with r = 0.97.
      Bland-Altman analysis indicated a bias of 0.22 favoring the CoaguChek XS, with
      95% limits of agreement -0.29 to 0.72. Passing and Bablok method comparison
      resulted in a slope of 0.91 (y = 0.91x + 0.02). An INR of <=0.5 was found between
      the methods in 89% of cases and 84% agreement was noted (kappa = 0.69).
      CONCLUSION: Comparing the capillary INR laboratory results to studies involving a
      venous specimen, the capillary specimen performed with equivalence. Thus, a
      capillary citrate specimen can be collected from the same finger-stick used to
      perform the POC INR for confirmation in the laboratory. This avoids the trauma of
      a venous collection in such a situation.

PMID- 30216711
TI  - Rates of Synthetic Cannabinoid Use in Adolescents Admitted to a Treatment
      Facility.
AB  - Objective: Many forms of synthetic marijuana are available in the United States
      for recreational use. Although the composition of these synthetic forms is
      unclear, consumption has been on the rise among adolescents. The objective of
      this study is to understand the usage rates and identify the reasons and risk
      factors for synthetic cannabinoid use. Methods: We recruited 637 adolescents
      (aged 13 to 17 years) admitted to the Children's Recovery Center, Norman,
      Oklahoma, from August 11, 2014, to March 30, 2016, for the study. Descriptive
      statistics and Pearson chi2 test were used to analyze the data. Logistic
      regression and adjusted odds ratio (OR) were performed to determine the risk
      factors for synthetic marijuana use. Results: The mean age of synthetic
      cannabinoid users was 16 years. Increased prevalence of synthetic marijuana use
      was observed in 16- to 17-year-old adolescent males, in the white population, and
      in individuals living in urban areas. Synthetic marijuana was preferred by
      subjects over the regular form, as it is less expensive, produces a better high,
      is undetectable on drug tests, and is perceived as legal. Male sex (OR = 2.63, P
      < .0001), aged 16 to 17 years (OR = 1.99, P < .0001), and residing in an urban
      locality (OR = 1.57, P = .05) were identified as risk factors for consuming
      synthetic marijuana. Adolescents who use synthetic marijuana are more at risk of
      having substance use disorder (OR = 11.87, P < .0001) than those who do not.
      Conclusions: Synthetic marijuana use is increasing in the adolescent age group
      and could potentially have a negative impact on the health of teenagers. Hence,
      enforcing strict laws against synthetic marijuana use and promoting awareness
      programs targeting adolescents would be beneficial..

PMID- 30216712
TI  - Clinical Features and Longitudinal Prognosis of Ultra-Rapid-Cycling Bipolar
      Disorder.

PMID- 30216713
TI  - Light-Driven Intermolecular Charge Transfer Induced Reactivity of
      Ethynylbenziodoxol(on)e and Phenols.
AB  - Ethynylbenziodoxol(on)es (EBXs) have been widely used in organic synthesis as
      electrophilic alkyne-transfer reagents involving carbon- and heteroatom-based
      nucleophiles. However, potential reactions of EBXs with phenols remain
      uninvestigated. Here, we present the formation of ( Z)-2-iodovinyl phenyl ethers
      with excellent regio- and stereoselectivity through the reactivity between EBXs
      and phenols driven by visible light. We propose that this light-activated
      transformation proceeds through electron donor-acceptor complexes to enable new
      reactivity beyond existing mechanisms for alkynylation of carbon- and heteroatom
      based nucleophiles. This operationally robust process was employed for the
      synthesis of diverse ( Z)-2-iodovinyl phenyl ethers through irradiating a
      solution containing a phenyl-EBX, a phenol, and the base Cs2CO3 with a
      commercially available blue LED at room temperature. The ( Z)-2-iodovinyl phenyl
      ether products can be further stereospecifically functionalized to form
      trisubstituted alkenes, demonstrating the potential of these products en route to
      chemical complexity.

PMID- 30216714
TI  - Quantification of Pharmaceutical Related Biological Activity in Effluents from
      Wastewater Treatment Plants in UK and Japan.
AB  - While pharmaceuticals are now routinely detected in aquatic environments, we know
      little of the biological activity their presence might provoke. It is estimated
      that nearly 40% of all marketed pharmaceuticals are G protein-coupled receptors
      (GPCRs) acting pharmaceuticals. Here, we applied an in-vitro assay, called the
      TGFalpha shedding assay, to measure the biological activities of GPCRs-acting
      pharmaceuticals present in effluents from municipal wastewater treatment plants
      in the United Kingdom (UK) and Japan from 2014 to 2016. The results indicated
      that compounds were present in the wastewater with antagonistic activities
      against angiotensin (AT1), dopamine (D2), adrenergic (beta1), acetylcholine (M1),
      and histamine (H1) receptors in both countries. The most consistent and powerful
      antagonistic activity was against the H1, D2, and AT1 receptors at up to
      microgram-antagonist-equivalent quantity/L. Chemical analysis of the same UK
      samples was also conducted in parallel. Comparing the results of the bioassay
      with the chemical analysis indicated (1) the existence of other D2 or M1 receptor
      antagonists besides sulpiride (D2 antagonist) or pirenzepine (M1 antagonist) in
      wastewater and (2) that there might be a mixture effect between agonist and
      antagonistic activities against beta1 receptor. GPCR-acting pharmaceuticals
      should be paid more attention in the environmental monitoring and toxicity
      testing in future studies.

PMID- 30216715
TI  - Waveguide-Integrated Compact Plasmonic Resonators for On-Chip Mid-Infrared Laser
      Spectroscopy.
AB  - The integration of nanoplasmonic devices with a silicon photonic platform affords
      a new approach for efficient light delivery by combining the high field
      enhancement of plasmonics and the ultralow propagation loss of dielectric
      waveguides. Such a hybrid integration obviates the need for a bulky free-space
      optics setup and can lead to fully integrated, on-chip optical sensing systems.
      Here, we demonstrate ultracompact plasmonic resonators directly patterned atop a
      silicon waveguide for mid-infrared spectroscopic chemical sensing. The footprint
      of the plasmonic nanorod resonators is as small as 2 MUm2, yet they can couple
      with the mid-infrared waveguide mode efficiently. The plasmonic resonance is
      directly measured through the transmission spectrum of the waveguide with a
      coupling efficiency greater than 70% and a field intensity enhancement factor of
      over 3600 relative to the evanescent waveguide field intensity. Using this hybrid
      device and a tunable mid-infrared laser source, surface-enhanced infrared
      absorption spectroscopy of both a thin poly(methyl methacrylate) film and an
      octadecanethiol monolayer is successfully demonstrated.

PMID- 30216716
TI  - Enantiomer-Selective Molecular Sensing Using Racemic Nanoplasmonic Arrays.
AB  - Building blocks of life show well-defined chiral symmetry which has a direct
      influence on their properties and role in Nature. Chiral molecules are typically
      characterized by optical techniques such as circular dichroism (CD) where they
      exhibit signatures in the ultraviolet frequency region. Plasmonic nanostructures
      have the potential to enhance the sensitivity of chiral detection and translate
      the molecular chirality to the visible spectral range. Despite recent progress,
      to date, it remains unclear which properties plasmonic sensors should exhibit to
      maximize this effect and apply it to reliable enantiomer discrimination. Here, we
      bring further insight into this complex problem and present a chiral plasmonic
      sensor composed of a racemic mixture of gammadions with no intrinsic CD, but high
      optical chirality and electric field enhancements in the near-fields. Owing to
      its unique set of properties, this configuration enables us to directly
      differentiate phenylalanine enantiomers in the visible frequency range.

PMID- 30216717
TI  - Layer-Stacking-Driven Fluorescence in a Two-Dimensional Imine-Linked Covalent
      Organic Framework.
AB  - Schiff-condensation reactions carried out between 1,6-diaminopyrene (DAP) and the
      tritopical 1,3,5 benzenetricarbaldehyde (BTCA) or 2,4,6-triformylphloroglucinol
      (TP) ligands give rise to the formation of two-dimensional imine-based covalent
      organic frameworks (COFs), named IMDEA-COF-1 and -2, respectively. These
      materials show dramatic layer-packing-driven fluorescence in solid state arising
      from the three-dimensional arrangement of the pyrene units among layers. Layer
      stacking within these 2D-COF materials to give either eclipsed or staggered
      conformations can be controlled, at an atomic level through chemical design of
      the building blocks used in their synthesis. Theoretical calculations have been
      used to rationalize the different preferential packing between both COFs. IMDEA
      COF-1 shows green emission with absolute photoluminescence quantum yield of 3.5%
      in solid state. This material represents the first example of imine-linked 2D-COF
      showing emission in solid state.

PMID- 30216718
TI  - Multifunctional Protein Materials and Microreactors using Low Complexity Domains
      as Molecular Adhesives.
AB  - Recent findings indicate that a class of disordered amino acid sequences promotes
      functional phase transition of biomolecules in nature. Such sequences consist of
      low complexity domains (LCDs) that are rich in specific amino acids. In this
      work, we exploit these sequences by conjugating them to soluble globular domains
      to develop molecular adhesives that enable sensitive, controlled self-assembly of
      these proteins into supramolecular architectures. In particular, we used the
      enzyme adenylate kinase and the green fluorescent protein as soluble domains, and
      we show that the addition of low complexity regions induces the formation of
      protein particles via a multistep process. This multistep pathway involves an
      initial liquid-liquid phase transition, which creates protein-rich droplets that
      mature into protein aggregates over time. These protein aggregates consist of
      permeable structures that maintain activity and release active soluble proteins.
      We show that the LCDs dictate specific noncovalent intermolecular interactions
      and phase properties that are largely independent of the given globular domain.
      We further demonstrate that this feature, together with the dynamic state of the
      initial dense liquid phase, allows one to directly assemble different globular
      domains within the same architecture, thereby enabling the generation of both
      static multifunctional biomaterials and dynamic microscale bioreactors.

PMID- 30216719
TI  - Reformatsky Reaction to Alkynyl N- tert-Butanesulfinyl Imines: Lewis Acid
      Controlled Stereodivergent Synthesis of beta-Alkynyl-beta-Amino Acids.
AB  - A highly diastereoselective Refortmatsky reaction to N- tert-butanesulfinyl
      propargylaldimines and ketimines is presented. The reaction proceeded with
      excellent yields and diastereoselectivities provided by the sulfinyl group in the
      presence of Me3Al. The use of TBSOTf as a Lewis acid promoter switched the sense
      of the stereoinduction. Thus, this methodology allowed the stereodivergent
      asymmetric synthesis of beta-alkynyl beta-amino acid derivatives, from the same
      sulfinyl configuration, by simply changing the Lewis acid promoter.

PMID- 30216720
TI  - Stability of the Gyroid Phase in Rod-Coil Systems via Thermodynamic Integration
      with Molecular Dynamics.
AB  - The stability of the gyroid phase in a coarse-grained model of rod-coil block
      copolymers is ascertained by using a field-based thermodynamic integration method
      to calculate free-energy differences between competing phases. The scope of the
      original methodology is expanded in terms of both its implementation by designing
      guiding fields suitable for molecular dynamics simulations (besides Monte Carlo
      simulations) and its applications by describing the formation of bicontinuous
      phases with linear rod-coil amphiphilic chains and with bolaamphiphilic
      molecules. For both types of systems, results are presented that complement those
      from previous studies, providing a quantitative metric to pinpoint the conditions
      and molecular parameters that render the gyroid phase more stable than other
      competing morphologies.

PMID- 30216721
TI  - Electrochemical Mechanism and Effect of Carbon Nanotubes on the Electrochemical
      Performance of Fe1.19(PO4)(OH)0.57(H2O)0.43 Cathode Material for Li-Ion
      Batteries.
AB  - A hydrothermal synthesis route was used to synthesize iron(III) phosphate
      hydroxide hydrate-carbon nanotube composites. Carbon nanotubes (CNT) were mixed
      in solution with Fe1.19(PO4)(OH)0.57(H2O)0.43 (FPHH) precursors for one-pot
      hydrothermal reaction leading to the FPHH/CNT composite. This produces a highly
      electronic conductive material to be used as a cathode material for Li-ion
      battery. The galvanostatic cycling analysis shows that the material delivers a
      specific capacity of 160 mAh g-1 at 0.2 C (0.2 Li per fu in 1 h), slightly
      decreasing with increasing current density. A high charge-discharge cyclability
      is observed, showing that a capacity of 120 mAh g-1 at 1 C is maintained after
      500 cycles. This may be attributed to the microspherical morphology of the
      particles and electronic percolation due to CNT but also to the unusual insertion
      mechanism resulting from the peculiar structure of FPHH formed by chains of
      partially occupied FeO6 octahedra connected by PO4 tetrahedra. The mechanism of
      the first discharge-charge cycle was investigated by combining operando X-ray
      diffraction and 57Fe Mossbauer spectroscopy. FPHH undergoes a monophasic reaction
      with up to 10% volume changes based on the Fe3+/Fe2+ redox process. However, the
      variations of the FPHH lattice parameters and the 57Fe quadrupole splitting
      distributions during the Li insertion-deinsertion process show a two-step
      behavior. We propose that such mechanism could be due to the existence of
      different types of vacant sites in FPHH, including vacant "octahedral" sites (Fe
      vacancies) that improve diffusion of Li by connecting the one-dimensional
      channels.

PMID- 30216722
TI  - Design and Synthesis of Novel Amino-triazine Analogues as Selective Bruton's
      Tyrosine Kinase Inhibitors for Treatment of Rheumatoid Arthritis.
AB  - Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of
      multiple diseases, such as B-cell malignances, asthma, and rheumatoid arthritis.
      A series of novel aminotriazines were identified as highly selective inhibitors
      of BTK by a scaffold-hopping approach. Subsequent SAR studies of this series
      using two conformationally different BTK proteins, an activated form of BTK and
      an unactivated form of BTK, led to the discovery of a highly selective BTK
      inhibitor, 4b. With significant efficacy in models in vivo and good ADME and
      safety profiles, 4b was advanced into preclinical studies.

PMID- 30216723
TI  - Oxidation State Distributions Provide Insight into Parameters Directing the
      Assembly of Metal-Organic Nanocapsules.
AB  - Two structurally analogous Mn-seamed C-alkylpyrogallol[4]arene (PgC n)-based
      metal-organic nanocapsules (MONCs) have been synthesized under similar reaction
      conditions and characterized by crystallographic, electrochemical, and magnetic
      susceptibility techniques. Both MONCs contain 24 Mn centers, but, somewhat
      surprisingly, marked differences in oxidation state distribution are observed
      upon analysis. One MONC contains exclusively MnII ions, while the other is a
      mixed-valence MnII/ MnIII assembly. We propose that these disparate oxidation
      state distributions arise from slight differences in pH achieved during
      synthesis, a factor that may lead to many spectacular new MONCs (and associated
      host-guest chemistries).

PMID- 30216724
TI  - Dehydration Pathways for Glucose and Cellobiose During Fast Pyrolysis.
AB  - A full understanding of all possible elementary reactions applicable to cellulose
      fast pyrolysis is key to developing a comprehensive kinetic model for fast
      pyrolysis of cellulose. Since water is an observed product of fast pyrolysis of
      cellulose, the energetics of the dehydration reactions of cellulose were explored
      computationally by using density functional theory. Glucose and cellobiose were
      selected as the cellulose model compounds. The four water loss mechanisms studied
      are Maccoll elimination, Pinacol ring contraction, cyclic Grob fragmentation, and
      alcohol condensation, some of which have not been considered previously in the
      literature. Levoglucosan formation via alcohol condensation has the lowest
      calculated free-energy barrier (50.4 kcal mol-1) for glucose dehydration. All
      other water loss reactions have calculated free-energy barriers greater than 60
      kcal mol-1. Cellobiose dehydration shows similar trends to those of glucose,
      suggesting that these reactions are applicable to glucooligosaccharides with
      higher degrees of polymerization. Secondary reactions of dehydrated glucose and
      dehydrated cellobiose via retro-Diels-Alder and aldol rearrangement mechanisms
      are also explored computationally.

PMID- 30216725
TI  - Boosting Ethane/Ethylene Separation within Isoreticular Ultramicroporous Metal
      Organic Frameworks.
AB  - The separation of ethane from its analogous ethylene is of great importance in
      the petrochemical industry, but very challenging and energy intensive. Adsorptive
      separation using C2H6-selective porous materials can directly produce high-purity
      C2H4 in a single operation but suffers from poor selectivity. Here, we report an
      approach to boost the separation of C2H6 over C2H4, involving the control of pore
      structures in two isoreticular ultramicroporous metal-organic framework (MOF)
      materials with weakly polar pore surface for strengthened binding affinity toward
      C2H6 over C2H4. Under ambient conditions, the prototypical compound shows a very
      small uptake difference and selectivity for C2H6/C2H4, whereas its smaller-pore
      isoreticular analogue exhibits a quite large uptake ratio of 237% (60.0/25.3 cm3
      cm-3), remarkably increasing the C2H6/C2H4 selectivity. Neutron powder
      diffraction studies clearly reveal that the latter material shows self-adaptive
      sorption behavior for C2H6, which enables it to continuously maintain close van
      der Waals contacts with C2H6 molecules in its optimized pore structure, thus
      preferentially binds C2H6 over C2H4. Gas sorption isotherms, crystallographic
      analyses, molecular modeling, selectivity calculation, and breakthrough
      experiment comprehensively demonstrate this unique MOF material as an efficient
      C2H6-selective adsorbent for C2H4 purification.

PMID- 30216726
TI  - Understanding Phase Behavior of Nearly Energetically Equivalent Polymorphs To
      Achieve Controlled Crystallization for a Nav1.7 Pain Inhibitor Compound.
AB  - GENE-A, a Nav1.7 inhibitor compound with analgesic activity, was developed as a
      crystalline anhydrate, for which two polymorphic forms, I and II, were
      discovered. The two forms were found to possess very similar free energies as
      determined experimentally with Form II being thermodynamically stable above 25 
      degrees C based on solubility measurements. A detailed solid-state
      characterization was conducted to determine the relative stability of these solid
      forms, and both thermodynamic and kinetic pathways (slurry bridging and
      crystallization) were evaluated. Form II was obtained as the final form in
      competitive slurries at RT. The outcome of crystallization experiments in terms
      of the solid form obtained was complicated and yielded variable results depending
      on the form of the starting material and that of the seeds. Form II was
      reproducibly obtained as the end product in unseeded experiments and in those
      with Form II as seeds and starting material, while Form I was obtained in all
      other seeded experiments. On the basis of the experimental data, a controlled
      crystallization strategy was developed, wherein Form II was used both as starting
      material and seeds to reproducibly obtain the desired form upon scale-up.

PMID- 30216727
TI  - Direct Characterization of Near-Field Coupling in Gap Plasmon-Based Metasurfaces.
AB  - Metasurfaces based on gap surface-plasmon resonators allow one to arbitrarily
      control the phase, amplitude, and polarization of reflected light with high
      efficiency. However, the performance of densely packed metasurfaces is reduced,
      often quite significantly, in comparison with simple analytical predictions. We
      argue that this reduction is mainly because of the near-field coupling between
      metasurface elements, which results in response from each element being different
      from the one anticipated by design simulations, which are commonly conducted for
      each individual element being placed in an artificial periodic arrangement. In
      order to study the influence of near-field coupling, we fabricate meta-elements
      of varying sizes arranged in quasi-periodic arrays so that the immediate
      environment of same size elements is different for those located in the middle
      and at the border of the arrays. We study the near-field using a phase-resolved
      scattering-type scanning near-field optical microscopy (s-SNOM) and conducting
      numerical simulations. By comparing the near-field maps from elements of the same
      size but different placements we evaluate the near-field coupling strength, which
      is found to be significant for large and densely packed elements. This technique
      is quite generic and can be used practically for any metasurface type in order to
      precisely measure the near-field response from each individual element and
      identify malfunctioning ones, providing feedback to their design and fabrication,
      thereby allowing one to improve the efficiency of the whole metasurface.

PMID- 30216729
TI  - Modifying a Commonly Expressed Endocytic Receptor Retargets Nanoparticles in
      Vivo.
AB  - Nanoparticles are often targeted to receptors expressed on specific cells, but
      few receptors are (i) highly expressed on one cell type and (ii) involved in
      endocytosis. One unexplored alternative is manipulating an endocytic gene
      expressed on multiple cell types; an ideal gene would inhibit delivery to cell
      type A more than cell type B, promoting delivery to cell type B. This would
      require a commonly expressed endocytic gene to alter nanoparticle delivery in a
      cell type-dependent manner in vivo; whether this can occur is unknown. Based on
      its microenvironmental regulation, we hypothesized Caveolin 1 (Cav1) would exert
      cell type-specific effects on nanoparticle delivery. Fluorescence was not
      sensitive enough to investigate this question, and as a result, we designed a
      platform named QUANT to study nanoparticle biodistribution. QUANT is 108* more
      sensitive than fluorescence and can be multiplexed. By measuring how 226 lipid
      nanoparticles (LNPs) delivered nucleic acids to multiple cell types in vivo in
      wild-type and Cav1 knockout mice, we found Cav1 altered delivery in a cell-type
      specific manner. Cav1 knockout did not alter LNP delivery to lung and kidney
      macrophages but substantially reduced LNP delivery to Kupffer cells, which are
      liver-resident macrophages. These data suggest caveolin-mediated endocytosis of
      nanomedicines by macrophages varies with tissue type. These results suggest
      manipulating receptors expressed on multiple cell types can tune drug delivery.

PMID- 30216728
TI  - Oxygen-Rich Porous Carbon Derived from Biomass for Mercury Removal: An
      Experimental and Theoretical Study.
AB  - A porous carbon was synthesized by the combination of freeze-drying and CO2
      activation from starch. Nonthermal plasma was employed to quickly produce oxygen
      functional groups on a porous carbon surface. The plasma treatment has a
      negligible effect on the textural properties of the porous carbon. Fourier
      transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses
      suggested that the plasma treatment significantly increased the amount and
      promoted the evolution of oxygen groups on surface. The unique pore structure of
      porous carbon was proven favorable to effective oxygen loading. The elemental
      mercury (Hg0) adsorption ability of the oxygen enriched porous carbon was tested.
      The results indicated that the oxygen-rich porous carbon constitutes an effective
      sorbent for Hg0 removal. The excellent textural properties, surface atomic oxygen
      concentration, and the type of oxygen group are the three key factors for
      realizing high Hg0 removal performance. Density functional calculations were
      performed to understand the effect of oxygen groups on Hg0 adsorption. Carbonyl
      and ester groups are beneficial for Hg0 adsorption, whereas epoxy, carboxyl, and
      hydroxyl groups inhibit Hg0 adsorption. Plasma treatment enhances Hg0 adsorption
      by increasing the amount of ester and carbonyl groups on surface.

PMID- 30216730
TI  - Safety of 8-h time restricted feeding in adults with obesity.
AB  - This study examines the safety of time restricted feeding (TRF; 8-h feeding
      window/16-h fasting window daily) in obese adults. Twenty-three subjects
      participated in an 8-h TRF intervention for 12 weeks. Self-reported adverse
      events, body image perception, complete blood count and disordered eating
      patterns did not change from baseline to week 12. These findings suggest that
      consuming food within an 8-h window can safely facilitate weight loss in subjects
      with obesity.

PMID- 30216732
TI  - New and Emerging Therapies for Pulmonary Arterial Hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that causes
      right ventricular dysfunction and exercise limitation and progresses to death.
      New findings from translational studies have suggested alternative pathways for
      treatment. These avenues include sex hormones, genetic abnormalities and DNA
      damage, elastase inhibition, metabolic dysfunction, cellular therapies, and anti
      inflammatory approaches. Both novel and repurposed compounds with rationale from
      preclinical experimental models and human cells are now in clinical trials in
      patients with PAH. Findings from these studies will elucidate the pathobiology of
      PAH and may result in clinically important improvements in outcome. Expected
      final online publication date for the Annual Review of Medicine Volume 70 is
      January 27, 2019. Please see http://www.annualreviews.org/page/journal/pubdates
      for revised estimates.

PMID- 30216731
TI  - Alignment of Inhaled COPD Therapies with Published Strategies: Analysis of the
      GOLD Recommendations in SPIROMICS.
AB  - RATIONALE: Despite awareness of COPD treatment recommendations, uptake is poor.
      The Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)
      spans 2010-2016, providing an opportunity to assess integration of 2011 Global
      Initiative for Obstructive Lung Disease (GOLD) treatment strategies over time in
      a large observational cohort study. OBJECTIVE: To evaluate how COPD treatment
      aligns with 2011 GOLD strategies and determine factors associated with failure to
      align with recommendations. METHODS: Inhaled medication use collected via
      questionnaire annually for four years was compiled into therapeutic classes
      (LAMA, LABA, ICS and combinations). Medications were not modified by SPIROMICS
      investigators. 2011 GOLD COPD categories A, B, C, or D were assigned. Alignment
      of inhaler regimen to 1st/2nd line GOLD recommendations were determined,
      stratifying into recommendation aligned or nonaligned. Recommendation nonaligned
      participants were further stratified into overuse and underuse. RESULTS: Of 1721
      COPD participants, at baseline 52% of regimens aligned with GOLD recommendations.
      Among participants with nonaligned regimens, 46% reported underuse, predominately
      due to lack of long-acting inhaler in GOLD-D. Of the 54% reporting overuse, 95%
      were treated with nonindicated ICS-containing regimens. Among 431 participants
      with four years of follow-up data, recommendation alignment did not change over
      time. When comparing 2011 and 2017 recommendations, 47% did not align with either
      recommendations while 35% were in alignment with both recommendations.
      CONCLUSIONS: Among SPIROMICS COPD participants, nearly 50% reported inhaler
      regimens that did not align with GOLD recommendations. Nonalignment was driven
      largely by overuse of ICS-regimens in milder disease and lack of long-acting
      inhalers in severe disease.

PMID- 30216734
TI  - Cost-effectiveness of the Hall Technique in a Randomized Trial.
AB  - Clinical and patient-reported outcomes were reported for carious primary molars
      treated with the Hall technique (HT) as compared with conventional carious tissue
      removal and restorations (i.e., conventional restoration [CR]) in a 5-y
      randomized controlled practice-based trial in Scotland. We interrogated this data
      set further to investigate the cost-effectiveness of HT versus CR. A total of 132
      children who had 2 matched occlusal/occlusal-proximal carious lesions in primary
      molars ( n = 264 teeth) were randomly allocated to HT or CR, provided by 17
      general dental practitioners. Molars were followed up for a mean 5 y. A societal
      perspective was taken for the economic analysis. Direct dental treatment costs
      were estimated from a Scottish NHS perspective (an NHS England perspective was
      taken for a sensitivity analysis). Initial, maintenance, and retreatment costs,
      including rerestorations, endodontic treatments, and extractions, were estimated
      with fee items. Indirect/opportunity costs were estimated with time and travel
      costs from a UK perspective. The primary outcome was tooth survival. Secondary
      outcomes included 1) not having pain or needing endodontic treatments/extractions
      and 2) not needing rerestorations. Cost-effectiveness and acceptability were
      estimated from bootstrapped samples. Significantly more molars in HT survived
      (99%, 95% CI: 98% to 100%) than in CR (92%; 87% to 97%). Also, the proportion of
      molars retained without pain or requiring endodontic treatment/extraction was
      significantly higher in HT than CR. In the base case analysis (NHS Scotland
      perspective), cumulative direct dental treatment costs (Great British pound
      [GBP]) of HT were 24 GBP (95% CI: 23 to 25); costs for CR were 29 (17 to 46).
      From an NHS England perspective, the cost advantage of HT (29 GBP; 95% CI: 25 to
      34) over CR (107; 86 to 127) was more pronounced. Indirect/opportunity costs were
      significantly lower for HT (8 GBP; 95% CI: 7 to 9) than CR (19; 16 to 23). Total
      cumulative costs were significantly lower for HT (32 GBP; 95% CI: 31 to 34) than
      CR (49; 34 to 69). Based on a long-term practice-based trial, HT was more cost
      effective than CR with HT retained for longer and experiencing less complications
      at lower costs.

PMID- 30216735
TI  - Effects of citrus leaf extract on aortic vascular reactivity in repeatedly heated
      vegetable oil-induced hypertensive rats.
AB  - The prolonged intake of diet containing repeatedly heated vegetable oil can cause
      hypertension in the long run. In this study, the effects of citrus leaf extract
      (CLE) supplementation on vascular reactivity, plasma nitrite, and aortic
      structure in repeatedly-heated vegetable oil-induced hypertension rats were
      investigated. Male Sprague-Dawley rats (n = 56) were divided into seven groups
      corresponding to the respective diets. For 16 weeks, one group was given standard
      rat chow (control) while other groups were given diets containing 15% w/w of palm
      oil, fresh palm oil (FPO), five-time-heated palm oil (5HPO) and ten-time-heated
      palm oil (10HPO), with or without 0.15% w/w CLE incorporation (FPO+CLE, 5HPO+CLE
      or 10HPO+CLE). Plasma nitrite levels were measured before and at 16 weeks of
      treatment. After 16 weeks, the rats were sacrificed and aortae were harvested for
      measuring vascular reactivity and for microscopic study. CLE supplementation had
      significantly reduced the loss of plasma nitrite and attenuated the
      vasoconstriction response to phenylephrine in the 5HPO group but not in the 10HPO
      group. However, CLE had no significant effect on the vasorelaxation response to
      acetylcholine and sodium nitroprusside. The elastic lamellae of tunica media in
      5HPO, 10HPO, and 10HPO+CLE groups appeared disorganised and disrupted. Obtained
      findings suggested that CLE was able to enhance nitric oxide bioavailability that
      might dampen the vasoconstriction effect of phenylephrine.

PMID- 30216733
TI  - The Mutational Profile of Unicystic Ameloblastoma.
AB  - BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the
      mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2,
      or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive
      variant of ameloblastoma, amenable to more conservative treatment, and classified
      as a distinct entity. The aim of this study was to characterize the mutation
      profile of UAM ( n = 39) and to compare it to conventional AM ( n = 39). The
      associations between mutation status and recurrence probability were also
      analyzed. In the mandible, 94% of UAMs (29/31, including 8/8 luminal, 6/8
      intraluminal, and 15/15 mural subtypes) and 74% of AMs (28/38) revealed BRAF
      V600E mutations. Among the BRAF wild-type cases, 1 UAM showed a missense SMO
      mutation (p.L412F), whereas 2 NRAS (p.Q61R), 2 HRAS (p.Q61R), and 2 FGFR2
      (p.C383R) activating mutations were identified in AM. Of the 3 maxillary UAMs,
      only 1 revealed a BRAF V600E mutation. Taken together, our findings demonstrate
      high frequency of activating BRAF V600E mutations in both UAM and AM of the
      mandible. In maxillary UAMs, the BRAF V600E mutation prevalence appears to be
      lower as was shown for AM previously. It could therefore be argued that UAM and
      AM are part of the spectrum of the same disease. AMs without BRAF V600E mutations
      were associated with an increased rate of local recurrence ( P = 0.0003), which
      might indicate that routine mutation testing also has an impact on prognosis.

PMID- 30216737
TI  - Using Noble Gases to Assess the Ocean's Carbon Pumps.
AB  - Natural mechanisms in the ocean, both physical and biological, concentrate carbon
      in the deep ocean, resulting in lower atmospheric carbon dioxide. The signals of
      these carbon pumps overlap to create the observed carbon distribution in the
      ocean, making the individual impact of each pump difficult to disentangle. Noble
      gases have the potential to directly quantify the physical carbon solubility pump
      and to indirectly improve estimates of the biological organic carbon pump. Noble
      gases are biologically inert, can be precisely measured, and span a range of
      physical properties. We present dissolved neon, argon, and krypton data spanning
      the Atlantic, Southern, Pacific, and Arctic Oceans. Comparisons between deep
      ocean observations and models of varying complexity enable the rates of processes
      that control the carbon solubility pump to be quantified and thus provide an
      important metric for ocean model skill. Noble gases also provide a powerful means
      of assessing air-sea gas exchange parameterizations. Expected final online
      publication date for the Annual Review of Marine Science Volume 11 is January 3,
      2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised
      estimates.

PMID- 30216736
TI  - Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an ARDS
      Model with ECMO.
AB  - RATIONALE: There is wide variability in mechanical ventilation settings during
      ECMO in ARDS patients. Although lung rest is recommended to prevent further
      injury, there is no evidence to support it. OBJECTIVES: To determine whether near
      apneic ventilation decreases lung injury in a pig model of ARDS supported with
      ECMO. METHODS: Pigs (26-36kg; n=24) were anesthetized and connected to mechanical
      ventilation. In 18 animals lung injury was induced by a double-hit consisting in
      repeated saline lavages followed by 2 hours of injurious ventilation. Then,
      animals were connected to high-flow veno-venous ECMO, and randomized into 3
      groups: Non-protective (PEEP 5 cmH2O, tidal volume 10 ml/kg, respiratory rate 20
      bpm); Conventional-protective (PEEP 10 cmH2O, tidal volume 6 ml/kg, respiratory
      rate 20 bpm); Near-apneic (PEEP 10 cmH2O, driving pressure 10 cmH2O, respiratory
      rate 5 bpm). Six other pigs were used as Sham. All groups were maintained during
      the 24-hour study period. MEASUREMENTS AND MAIN RESULTS: Minute ventilation and
      mechanical power were lower in the Near-apneic group, but no differences were
      observed in oxygenation or compliance. Lung histology revealed less injury in the
      Near-apneic group. Extensive immunohistochemical staining for myofibroblasts and
      pro-collagen III was observed in the Non-protective group, with the Near-apneic
      group exhibiting the least alterations. Near-apneic group showed significantly
      less matrix-metalloproteinase-2 and -9 activity. Histological lung injury and
      fibroproliferation scores were positively correlated with driving pressure and
      mechanical power. CONCLUSIONS: In an ARDS model supported with ECMO, near-apneic
      ventilation decreased histologic lung injury and matrix-metalloproteinase
      activity, and prevented the expression of myofibroblast markers.

PMID- 30216738
TI  - Marine Metazoan Modern Mass Extinction: Improving Predictions by Integrating
      Fossil, Modern, and Physiological Data.
AB  - Evolution, extinction, and dispersion are fundamental processes affecting marine
      biodiversity. Until recently, studies of extant marine systems focused mainly on
      evolution and dispersion, with extinction receiving less attention. Past
      extinction events have, however, shaped the evolutionary history of marine
      ecosystems, with ecological and evolutionary legacies still evident in modern
      seas. Current anthropogenic global changes increase extinction risk and pose a
      significant threat to marine ecosystems, which are critical for human use and
      sustenance. The evaluation of these threats and the likely responses of marine
      ecosystems requires a better understanding of evolutionary processes that affect
      marine ecosystems under global change. Here, we discuss how knowledge of (a)
      changes in biodiversity of ancient marine ecosystems to past extinctions events,
      (b) the patterns of sensitivity and biodiversity loss in modern marine taxa, and
      (c) the physiological mechanisms underpinning species' sensitivity to global
      change can be exploited and integrated to advance our critical thinking in this
      area. Expected final online publication date for the Annual Review of Marine
      Science Volume 11 is January 3, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30216739
TI  - Arctic and Antarctic Sea Ice Change: Contrasts, Commonalities, and Causes.
AB  - Arctic sea ice has declined precipitously in both extent and thickness over the
      past four decades; by contrast, Antarctic sea ice has shown little overall
      change, but this masks large regional variability. Climate models have not
      captured these changes. But these differences do not represent a paradox.The
      processes governing, and impacts of, natural variability and human-induced
      changes differ markedly at the poles largely because of the ways in which
      differences in geography control the properties of and interactions among the
      atmosphere, ice, and ocean. The impact of natural variability on the ice cover is
      large at both poles, so modeled ice trends are not entirely inconsistent with
      contributions from both natural variability and anthropogenic forcing. Despite
      this concurrence, the coupling of natural climate variability, climate feedbacks,
      and sea ice is not well understood, and significant biases remain in model
      representations of the ice cover and the processes that drive it. Expected final
      online publication date for the Annual Review of Marine Science Volume 11 is
      January 3, 2019. Please see http://www.annualreviews.org/page/journal/pubdates
      for revised estimates.

PMID- 30216740
TI  - Chronic Asthma and Bronchitis without Persistent Airflow Limitation May Have Been
      Misclassified as Chronic Obstructive Pulmonary Disease Using Administrative Data.

PMID- 30216742
TI  - Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging.
AB  - Mitochondria are critical organelles responsible for regulating the metabolic
      status of skeletal muscle. These organelles exhibit remarkable plasticity by
      adapting their volume, structure, and function in response to chronic exercise,
      disuse, aging, and disease. A single bout of exercise initiates signaling to
      provoke increases in mitochondrial biogenesis, balanced by the onset of organelle
      turnover carried out by the mitophagy pathway. This accelerated turnover ensures
      the presence of a high functioning network of mitochondria designed for
      optimalATPsupply, with the consequence of favoring lipid metabolism, maintaining
      muscle mass, and reducing apoptotic susceptibility over the longer term.
      Conversely, aging and disuse are associated with reductions in muscle mass that
      are in part attributable to dysregulation of the mitochondrial network and
      impaired mitochondrial function. Therefore, exercise represents a viable,
      nonpharmaceutical therapy with the potential to reverse and enhance the impaired
      mitochondrial function observed with aging and chronic muscle disuse. Expected
      final online publication date for the Annual Review of Physiology Volume 81 is
      February 10, 2019. Please see http://www.annualreviews.org/page/journal/pubdates
      for revised estimates.

PMID- 30216741
TI  - Difficulties with emotion regulation, mindfulness, and substance use disorder
      severity: the mediating role of self-regulation of attention and acceptance
      attitudes.
AB  - BACKGROUND: Theoretical frameworks postulate that mindfulness represents a
      relevant therapeutic process in substance use disorders (SUDs), especially in
      treating difficulties with emotion regulation (DER). Nonetheless, it remains
      unclear how mindfulness dimensions, particularly self-regulation of attention and
      acceptance attitudes, are implicated in the well-validated relationship between
      DER and SUDs. It is also uncertain whether mindfulness is considered a common
      protective factor for SUDs. OBJECTIVES: To investigate the mediating role of
      mindfulness in the relationships between DER and SUDs among treatment-seeking
      patients with alcohol use disorder (AUD). METHODS: Two related domains of
      mindfulness were evaluated: (a) self-regulation of attention (Mindful Attention
      Awareness Scale, MAAS) and (b) acceptance attitudes (Five Facet Mindfulness
      Questionnaire, FFMQ, nonjudging, and nonreactivity subscales)). Two-hundred and
      forty-four (149 males and 95 females) participants with AUD were assessed.
      Mindfulness, DER, and SUD severity (alcohol, benzodiazepines, and other drugs)
      were assessed after a 2-week detoxification period. Three independent multiple
      parallel mediational models, controlling for the heterogeneity of sample
      characteristics, were proposed. RESULTS: MAAS and FFMQ nonjudging were
      significant mediators of the relationship between DER and AUD severity.
      Mindfulness dimensions and DER were not related to other drug use disorders. DER
      represented a relevant factor in explaining the severity of benzodiazepine use
      disorder, although mindfulness was not significantly related to it. CONCLUSION:
      Mindfulness appears to be a protective factor for DER effects on AUD. Future
      research should evaluate additional dysfunctional processes to clarify how unique
      dimensions are implicated in the development and maintenance of different SUDs.

PMID- 30216743
TI  - Cysteine-Based Redox Sensing and Its Role in Signaling by Cyclic Nucleotide
      Dependent Kinases in the Cardiovascular System.
AB  - Oxidant molecules are produced in biological systems and historically have been
      considered causal mediators of damage and disease. While oxidants may contribute
      to the pathogenesis of disease, evidence continues to emerge that shows these
      species also play important regulatory roles in health. A major mechanism of
      oxidant sensing and signaling involves their reaction with reactive cysteine
      thiols within proteins, inducing oxidative posttranslational modifications that
      can couple to altered function to enable homeostatic regulation. Protein kinase A
      and protein kinase G are regulated by oxidants in this way, and this review
      focuses on our molecular-level understanding of these events and their role in
      regulating cardiovascular physiology during health and disease. Expected final
      online publication date for the Annual Review of Physiology Volume 81 is February
      10, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for
      revised estimates.

PMID- 30216744
TI  - The Placebo Effect in Pain Therapies.
AB  - Pharmacological strategies for pain management have primarily focused on
      dampening ascending neurotransmission and on opioid receptor-mediated therapies.
      Little is known about the contribution of endogenous descending modulatory
      systems to clinical pain outcomes and why some patients are mildly affected while
      others suffer debilitating pain-induced dysfunctions. Placebo effects that arise
      from patients' positive expectancies and the underlying endogenous modulatory
      mechanisms may in part account for the variability in pain experience and
      severity, adherence to treatment, distinct coping strategies, and chronicity.
      Expectancy-induced analgesia and placebo effects in general have emerged as
      useful models to assess individual endogenous pain modulatory systems. Different
      systems and mechanisms trigger placebo effects that highly impact pain
      processing, clinical outcomes, and sense of well-being. This review illustrates
      critical elements of placebo mechanisms that inform the methodology of clinical
      trials, the discovery of new therapeutic targets, and the advancement of
      personalized pain management. Expected final online publication date for the
      Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please
      see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30216746
TI  - Editorial Comment.

PMID- 30216745
TI  - The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder.
AB  - New approaches to the neurobiology of posttraumatic stress disorder (PTSD) are
      needed to address the reported crisis in PTSD drug development. These new
      approaches may require the field to move beyond a narrow fear-based perspective,
      as fear-based medications have not yet demonstrated compelling efficacy.
      Antidepressants, particularly recent rapid-acting antidepressants, exert complex
      effects on brain function and structure that build on novel aspects of the
      biology of PTSD, including a role for stressrelated synaptic dysconnectivity in
      the neurobiology and treatment ofPTSD. Here, we integrate this perspective within
      a broader framework-in other words, a dual pathology model of (a) stress-related
      synaptic loss arising from amino acid-based pathology and (b) stress-related
      synaptic gain related to monoamine-based pathology. Then, we summarize the
      standard and experimental (e.g., ketamine) pharmacotherapeutic options for PTSD
      and discuss their putative mechanism of action and clinical efficacy. Expected
      final online publication date for the Annual Review of Pharmacology and
      Toxicology Volume 59 is January 6, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30216747
TI  - Resveratrol preserves mitochondrial function in a human post-mitotic cell model.
AB  - Dysfunctions caused by genetic defects in the mitochondrial DNA (mtDNA) of humans
      are called mitochondrial diseases; however, mtDNA mutations are also associated
      with aging and age-related diseases. Here, we present an original cellular model
      that allows gathering information on molecules that might contrast or prevent
      mitochondrial dysfunctions and their related diseases. This model allowed us to
      show that resveratrol (RSV), a phytochemical present in food, exerts protective
      effects at low concentrations on resting human fibroblasts carrying dysfunctional
      respiratory chain Complex I. Cells were maintained both in resting condition, to
      mimic the high energy demanding post-mitotic tissues (serum absence and
      gramicidin presence), and under glucose deficiency to push the synthesis of ATP
      via oxidative phosphorylation. Pre-incubation with RSV prolonged the viability of
      the fibroblasts exposed to rotenone, a well-known specific inhibitor of the
      respiratory chain Complex I, and decreased mitochondrial fragmentation. It
      significantly prevented the oxidative phosphorylation impairment indirectly
      caused by the rotenone-mediated Complex I inhibition, allowing for an almost
      complete preservation of the cellular ATP level. Indeed, RSV limited the rotenone
      induced reactive oxygen species increase, allowing for the maintenance of a
      functional mitochondrial membrane potential. These findings indicate the
      potential usage of resveratrol to prevent or possibly treat many disorders, in
      which the bioenergetic defects and oxidative stress are the primary
      (mitochondrial encephalomyopathy), or the secondary (age-related diseases) causes
      of the pathology; and to also assist cell senescence during aging.

PMID- 30216748
TI  - Developing an openly accessible multi-dimensional small area index of 'Access to
      Healthy Assets and Hazards' for Great Britain, 2016.
AB  - Health geographers have been long concerned with understanding how the
      accessibility of individuals to certain environmental features may influence
      health and wellbeing. Such insights are increasingly being adopted by policy
      makers for designing healthy neighbourhoods. To support and inform decision
      making, there is a need for small area national level data. This paper details
      the creation of a suite of open access health indicators, including a novel
      multidimensional index summarising 14 health-related features of neighbourhoods
      for Great Britain. We find no association of our overall index with physical
      health measures, but a significant association to mental wellbeing.

PMID- 30216749
TI  - Self-assessed confidence of students on selected midwifery skills: Comparing
      diploma and bachelors programmes in one province of India.
AB  - OBJECTIVE: There are two integrated pre-service education programmes for nurses
      and midwives in India; a diploma in General Nursing and Midwifery (GNM) and
      bachelor's in nursing (B.Sc. nursing). This study assessed and compared
      confidence of final-year students from these two programmes for selected
      midwifery skills from the list of midwifery competencies given by the
      International Confederation of Midwives (ICM). DESIGN: A cross-sectional survey.
      PARTICIPANTS: 633 final-year students, from 25 educational institutions randomly
      selected, stratified by the type of programme (diploma/bachelor), and ownership
      (private/government) from the Gujarat province. DATA COLLECTION AND ANALYSIS:
      Students assessed their confidence on a 4-point scale, in four midwifery
      competency domains-antepartum, intrapartum, postpartum, and newborn care. Skill
      statements were reduced to subscales for each competency domain separately
      through Principle Component Analysis. Crude and adjusted odds ratios with 95% CI
      were calculated for students with high confidence (>=75th percentile on each
      subscale) and not high (all others) between diploma and bachelor students.
      FINDINGS: The diploma students were 2-4 times more likely to have high confidence
      on all subscales under antepartum, intrapartum, postpartum and newborn care
      compared to the bachelor students. Though both groups had less hands-on clinical
      practice during their education, more diploma students could fulfil the
      requirements of attending recommended number of births compared to the bachelor
      students. CONCLUSION: Overall the students of the general nursing and midwifery
      (GNM) programme have higher confidence in skills for antepartum, intrapartum,
      newborn and postpartum care. One important reason is more hands-on clinical
      practice for the diploma compared to the bachelor students.

PMID- 30216750
TI  - Losing blood and saving lives: Recognising the problems and impacts.

PMID- 30216751
TI  - Covering the Prescription Drug Monitoring Program Gap: Using Shared Decision
      Making to Reduce Dental Opioid Prescriptions.

PMID- 30216752
TI  - Craniofacial Trauma Is Associated With Significant Psychosocial Morbidity 1 Year
      Post-Injury.
AB  - PURPOSE: The face and head play critical roles in one's sense of self and body
      image; as such, facial, head, and scalp injuries and potential associated
      disfigurement can lead to particular difficulties in coping. This study examined
      the psychosocial outcomes of patients with craniofacial (CF) trauma 1 year after
      injury and compared these outcomes with those of other traumatically injured
      patients who did not sustain such injuries. It was hypothesized that participants
      in the CF injury group would have worse outcomes than those without CF trauma.
      MATERIALS AND METHODS: This prospective longitudinal study included patients at
      least 18 years of age admitted to the trauma service of a level I trauma center
      for at least 24 hours. Demographic and injury-related variables were collected.
      CF injury was determined by International Classification of Diseases, Ninth
      Revision codes. Outcomes were measured at baseline and at 12 months and included
      depression, post-traumatic stress disorder (PTSD), alcohol use, and pain
      severity. Paired t tests and logistic regression were used for analysis. RESULTS:
      Fifteen percent (n = 35) of the study sample (N = 230) had CF injuries. Those
      with CF injuries had lower income, higher injury severity, and higher intensive
      care unit admission rates. The CF and non-CF trauma groups did not differ in
      rates of depression or PTSD at either time point. However, participants with CF
      trauma had higher odds of risky alcohol use than those without CF trauma at
      baseline and lower odds of a higher pain severity score at baseline and 12
      months. CONCLUSIONS: The groups did not differ in depression and PTSD. However,
      rates of depression, PTSD, alcohol use, and physical pain were higher than
      expected for the 2 groups. Given the high rate of psychological morbidity found
      after CF trauma, patients with these injuries should be screened for symptoms
      soon after injury and provided with resources for treatment.

PMID- 30216753
TI  - Three-dimensional forces beyond actomyosin contraction: lessons from fly
      epithelial deformation.
AB  - Epithelium undergoes complex deformations during morphogenesis. Many of these
      deformations rely on the remodelling of apical cell junctions by actomyosin-based
      contractile force and this has been a major research interest for many years.
      Recent studies have shown that cells can use additional mechanisms that are not
      directly driven by actomyosin contractility to alter cell shape and movement, in
      three-dimensional (3D) space and time. In this review, we focus on a number of
      these mechanisms, including basolateral cellular protrusion, lateral shift of
      cell polarity, cytoplasmic flow, regulation of cell volume, and force
      transmission between cell-cell adhesion and cell-extracellular matrix adhesion,
      and describe how they underlie Drosophila epithelia deformations.

PMID- 30216754
TI  - Integrating spiritual care into nursing education and practice: Strategies
      utilizing Open Journey Theory.
AB  - Throughout nursing, spirituality is a recognized domain of patient care, but
      nurses feel ill prepared by their nursing education to provide care that is
      spiritual in nature to patients and their families. Incorporating spiritual care
      into nursing curricula is challenging in light of the amount of topics for
      healthcare learning. Open Journey Theory is based on the merging of two grounded
      theories, one teaching and one learning theory, and is the suggested framework
      for integrating spirituality and spiritual care across all levels of nursing
      education. Specially chosen readings (books, articles), activities (role-plays,
      discussion groups), and assignments (journaling, writing papers, giving reports)
      can be integrated into already existing courses. By utilizing the three stages of
      preparing, connecting, and reflecting to frame student learning, nurse educators
      can introduce and build on spiritual concepts from the simple to the complex over
      the course of the entire nursing program.

PMID- 30216755
TI  - Exploring the role of physical activity and exercise for managing vascular
      comorbidities in people with multiple sclerosis: A scoping review.
AB  - INTRODUCTION: Vascular comorbidities are prevalent among people with multiple
      sclerosis (MS) and have adverse disease-related consequences. In the general
      population, physical activity (PA) and exercise training have proven beneficial
      at all levels of vascular disease risk management. People with MS exhibit
      particularly low rates of PA; therefore, PA represents a modifiable health
      behavior for potentially managing vascular comorbidity risk in MS, and in turn,
      reducing disease burden. However, points of evidence justifying such an approach
      have yet to be summarized. OBJECTIVE: To conduct a scoping review of existing
      evidence linking PA and exercise training to potential modification of vascular
      comorbidities and related risk factors in people with MS. METHODS: We searched
      five electronic databases (PubMed, Ovid MEDLINE, Embase, PsycINFO, and CINAHL
      Plus) from inception to November 2017, for articles involving relevant vascular
      comorbidities (obesity, hyperlipidemia, heart disease, hypertension, and
      diabetes) in people with MS in conjunction with measures of PA, physical fitness,
      sedentary behavior, or exercise training. Studies were limited to English
      language and primary research articles. Data were extracted and summarized by
      comorbidity type and study design (observational vs. interventional). RESULTS:
      Our initial search identified 1028 articles; subsequent screening resulted in 34
      articles meeting the final inclusion criteria, including both observational (n =
      17) and interventional (n = 17) studies. Most of the articles reported on obesity
      (n = 29), although evidence surrounding hyperlipidemia (n = 5), arterial function
      and hypertension (n = 5), and diabetes (n = 5) was also identified. Data
      supporting a beneficial role for PA or exercise training could be drawn from each
      comorbidity category. Overall, 14 of the 17 observational studies identified
      (82.4%) reported an association between higher levels of PA or cardiorespiratory
      fitness, or decreased sedentary behavior, and better function of at least one
      risk factor related to vascular comorbid conditions in people with MS. The
      efficacy of exercise training in limiting vascular comorbidity risk and burden
      was dependent upon intervention type and duration, with 9 of 17 interventional
      studies (52.9%) reporting improvement in at least one relevant measure of
      vascular comorbidity in participants with MS. CONCLUSIONS: Evidence points to a
      potential relationship between PA and exercise and risk factors related to
      vascular comorbidities in people with MS. PA and exercise training interventions
      may represent an effective therapeutic strategy for managing vascular
      comorbidities in people with MS, justifying further investigation.

PMID- 30216756
TI  - Peginterferon beta-1a for the treatment of relapsing multiple sclerosis: A case
      series.
AB  - Interferon beta therapies have been effective in the treatment of relapsing forms
      of multiple sclerosis for over 2 decades. These therapies have varying routes and
      schedules of administration but broadly similar clinical and radiologic efficacy.
      The most commonly reported adverse effects are flu-like symptoms and injection
      site reactions. The most recent addition to the class is peginterferon beta-1a,
      which is administered subcutaneously every 2 weeks. Although clinically stable
      patients with multiple sclerosis may switch between platform therapies (such as
      interferons) based on tolerability or personal preference, few studies have
      explored the outcomes of switching. Herein I present 3 cases of patients who
      either initiated therapy with peginterferon beta-1a or switched from another
      interferon and had positive outcomes. With appropriate patient education and
      expectation setting regarding potential flu-like symptoms and injection-site
      reactions, peginterferon beta-1a may be a beneficial alternative for patients who
      prefer less frequent injections.

PMID- 30216757
TI  - An optimal protocol for measurement of corticospinal excitability, short
      intracortical inhibition and intracortical facilitation in the rectus femoris.
AB  - The study aimed to determine the optimal application of single- and paired-pulse
      transcranial magnetic stimulation (TMS) in the rectus femoris. Twenty-nine male
      adults participated in the study, which involved 5 separate experiments.
      Experiments 1 to 3 assessed the effect of conditioning stimulus (CS) intensity
      (60, 70, 80 and 90% active motor threshold, AMT), contraction strength (5, 10, 20
      and 50% maximum voluntary contraction, MVC), and inter-stimulus interval (ISI, 2
      5 ms for short-interval intracortical inhibition, SICI and 10-15 ms for
      intracortical facilitation, ICF) on SICI and ICF. In Experiment 4, 30
      measurements of corticospinal excitability (CSE), SICI and ICF were recorded,
      with the minimum number of consecutive measurements required as a probability of
      falling within the 95% CI determined. In Experiment 5, within- and between-day
      reliability of CSE, SICI and ICF was assessed. The results suggest that for SICI,
      a CS of 70% AMT, ISI of 2 ms, and contraction strength of 5 or 10% MVC induces
      the greatest level of inhibition. Negligible differences in ICF were seen across
      stimulus variables. The minimum number of measurements required to obtain an
      accurate estimate of CSE, SICI and ICF was 21, 18 and 17, respectively. Using the
      optimal stimulus variables and number of measurements, CSE, SICI and ICF can be
      measured reliably both within- and between-days (intraclass correlation
      coefficient, ICC >= 0.87, >=0.74, and >=0.61, respectively). The current findings
      can be used to guide future investigations using single- and paired-pulse TMS to
      elicit responses in the rectus femoris.

PMID- 30216758
TI  - Towards an integrated functional and epileptological approach in the management
      of meningioangiomatosis.

PMID- 30216759
TI  - Arterial spin labeling MR imaging for the clinical detection of cerebellar
      hypoperfusion in patients with spinocerebellar degeneration.
AB  - PURPOSE: The aim of this study was to evaluate the clinical utility of arterial
      spin labeling (ASL) magnetic resonance imaging (MRI) for the detection of
      cerebellar hypoperfusion in patients with spinocerebellar degeneration (SCD).
      METHODS: Regional cerebral blood flow (CBF) were obtained from ASL and 123I-IMP
      single-photon emission computed tomography (SPECT) images by volume-of-interest
      analysis in patients with SCD (n = 16). Regional CBF were also measured by ASL in
      age-matched controls (n = 19) and by SPECT in separate controls (n = 17). The
      cerebellar CBF values were normalized to the CBF values for the whole gray matter
      (nCBF) in ASL and SPECT. RESULTS: The mean cerebellar nCBF measured by ASL was
      lower in patients with SCD (0.70 +/- 0.09) than in the controls (0.91 +/- 0.05)
      (p < 0.001), which was consistent with the comparison using SPECT (0.82 +/- 0.05
      vs. 0.98 +/- 0.05, p < 0.001). The cerebellar nCBF measured by ASL significantly
      correlated with that determined by SPECT in patients (r = 0.56, p < 0.001).
      CONCLUSIONS: ASL imaging showed decreased cerebellar blood flow, which correlated
      with that measured by SPECT, in patients with SCD. These findings suggest the
      clinical utility of noninvasive MRI with ASL for detecting cerebellar
      hypoperfusion in addition to atrophy, which would aid the diagnosis of SCD.

PMID- 30216760
TI  - Protective effect of Thai silk extracts on drug-induced phototoxicity in human
      epidermal A431 cells and a reconstructed human epidermis model.
AB  - Bombyx mori silk extracts, derived from the cocoon degumming process of draw and
      dye silk in the textile industry, are mainly composed of sericin protein. To add
      value to the Thai silk extracts, and hence the silk industry, a simple enrichment
      process was recently developed and the enriched silk extracts were then applied
      in nano-cosmeceutical products and nano-delivery systems. In this study, the
      protective effect of Thai silk extracts from three different strains of Bombyx
      mori on the drug-induced phototoxicity was evaluated in vitro using
      chlorpromazine (CPZ), a commonly used antipsychotic drug, as a representative
      phototoxic drug. The human epidermal A431 cell line and reconstructed human
      epidermis (RhE) model were used as the in vitro skin model. The silk extracts
      significantly improved the viability of A431 cells after CPZ exposure and
      ultraviolet A (UVA) irradiation, as shown by the significantly increased CPZ and
      UVA IC50 values and the decreased proportion of apoptotic cells. The protective
      effect of these silk extracts against the CPZ-induced UVA-phototoxicity in A431
      cells was associated with the attenuation of intracellular oxidative stress via
      an increased intracellular glutathione level. Likewise, the silk extracts
      exhibited a protective effect on the CPZ-induced UVA-phototoxicity in the RhE
      model, in terms of an improved tissue viability and attenuation of the released
      inflammatory cytokine, interleukin-1alpha. These findings support the potential
      usefulness of silk extracts in novel applications, especially in the protection
      of drug-induced phototoxicity.

PMID- 30216761
TI  - Effect of red light and near infrared laser on the generation of reactive oxygen
      species in primary dermal fibroblasts.
AB  - Irradiation with red light or near-infrared (NIR) lasers can bio-modulate
      cellular processes or revitalize injured tissues and therefore, widely been used
      for therapeutic interventions. Mechanistically, this cellular or biological
      process, referred as Photobiomodulation (PBM), is achieved by the generation of
      oxide free radicals in cells and tissues. This explorative study using red light
      (636 nm) and Near Infra-Red (NIR, 825 nm) laser at various irradiation exposures
      reckons the level of oxidative stress induced by these free radicals in human
      primary fibroblasts. Freshly isolated dermal fibroblasts were irradiated with red
      light and NIR at power densities of 74 and 104 mV/cm2, respectively and, at
      varying fluences ranging from 5 to 25 J/cm2. Cellular oxidative stress, measured
      by Reactive Oxygen Species (ROS) upon quantifying fluorescently labelled oxide
      free radicals in cells, detected considerable variations between the irradiation
      exposures of red light and NIR laser. The NIR laser demonstrated high levels of
      ROS at all fluences, except 10 J/cm2 indicating its ability in generating of two
      types of oxide radicals in dermal fibroblasts, often illustrated as biphasic
      response. Further, the responses of these cells to variable fluences of red light
      and NIR laser were measured to evaluate the immediate effect of PBM on cellular
      activity. The production of cellular energy coincides with the amount of
      oxidative stress, which was two-fold higher in cells irradiated with the NIR
      laser, as compared with the red light. This outcome indicates that the ROS
      production within biological systems are more dependent on the wavelength of the
      laser rather than its fluences. Further studies are required to avoid 'overdosing
      of PBM' and to analyse ROS qualitatively for making the best use of the red light
      and NIR laser in clinics.

PMID- 30216762
TI  - Determination of Hepatocellular Carcinoma and Characterization of Hepatic Focal
      Lesions with Adaptive Multi-Exponential Intravoxel Incoherent Motion Model.
AB  - PURPOSE: To distinguish hepatocellular carcinoma (HCC) from other types of
      hepatic lesions with the adaptive multi-exponential IVIM model. METHODS: 94
      hepatic focal lesions, including 38 HCC, 16 metastasis, 12 focal nodular
      hyperplasia, 13 cholangiocarcinoma, and 15 hemangioma, were examined in this
      study. Diffusion-weighted images were acquired with 13 b values (b = 0, 3, ...,
      500 s/mm2) to measure the adaptive multi-exponential IVIM parameters, namely,
      pure diffusion coefficient (D), diffusion fraction (fd), pseudo-diffusion
      coefficient (Di*) and perfusion-related diffusion fraction (fi) of the ith
      perfusion component. Comparison of the parameters of and their diagnostic
      performance was determined using Mann-Whitney U test, independent-sample t test,
      one-way analysis of variance, Z test and receiver-operating characteristic
      analysis. RESULTS: D, D1* and D2* presented significantly difference between HCCs
      and other hepatic lesions, whereas fd, f1 and f2 did not show statistical
      differences. In the differential diagnosis of HCCs from other hepatic lesions,
      D2* (AUC, 0.927) provided best diagnostic performance among all parameters.
      Additionally, the number of exponential terms in the model was also an important
      indicator for distinguishing HCCs from other hepatic lesions. In the benign and
      malignant analysis, D gave the greatest AUC values, 0.895 or 0.853, for
      differentiation between malignant and benign lesions with three or two
      exponential terms. Most parameters were not significantly different between
      hypovascular and hypervascular lesions. For multiple comparisons, significant
      differences of D, D1* or D2* were found between certain lesion types. CONCLUSION:
      The adaptive multi-exponential IVIM model was useful and reliable to distinguish
      HCC from other hepatic lesions.

PMID- 30216763
TI  - Sorcin a Potential Molecular Target for Cancer Therapy.
AB  - Sorcin (Soluble resistance related calcium binding protein) is a small soluble
      penta EF family (PEF) of calcium (Ca2+) binding protein (22,000 Da). It has been
      reported to play crucial roles in the regulation of calcium homeostasis,
      apoptosis, vesicle trafficking, cancer development, and multidrug resistance
      (MDR). Overexpression of sorcin has been reported to be associated with different
      cancers such as breast cancer, colorectal cancer, gastric cancer, leukemia, lung
      cancer, nasopharyngeal cancer, ovarian cancer, etc. Essentially, expression of
      sorcin has been found to be elevated in cancer cells as compared to normal cells,
      indicating that it has prominent role in cancer. Moreover, sorcin was found to be
      the regulator of various proteins that has an association with carcinogenesis
      including NF-kappaB, STAT3, Akt, ERK1/2, VEGF, MMPs, caspases, etc. Sorcin was
      also found to regulate apoptosis, as silencing of the same resulted in increased
      levels of proapoptotic genes and induced mitochondrial apoptotic pathway in
      cancer. Interestingly, mutations in the sorcin gene have been closely linked with
      poor overall survival in bladder cancer, brain lower-grade glioma, glioblastoma,
      glioblastoma multiforme, kidney renal clear cell carcinoma, and stomach
      adenocarcinoma. Additionally, overexpression of sorcin was also found to induce
      MDR against different chemotherapeutic drugs. All these findings mark the
      importance of sorcin in cancer development and MDR. Therefore, there is urgent
      need to explore the functional mechanism of sorcin and to analyze whether
      silencing of sorcin would able to chemosensitize MDR cells. The current review
      summarizes the structure, expression, and functions of sorcin and its importance
      in the regulation of various malignancies and MDR.

PMID- 30216764
TI  - Clinical Relevance of Genomic Changes in Recurrent Pediatric Solid Tumors.
AB  - PURPOSE: Relapsed/refractory pediatric cancers show poor prognosis; however,
      their genomic patterns remain unknown. To investigate the genetic mechanisms of
      tumor relapse and therapy resistance, we characterized genomic alterations in
      diagnostic and relapsed lesions in patients with relapsed/refractory pediatric
      solid tumors using targeted deep sequencing. PATIENTS AND METHODS: A targeted
      sequencing panel covering the exons of 381 cancer genes was used to characterize
      19 paired diagnostic and relapsed samples from patients with relapsed/refractory
      pediatric solid tumors. RESULTS: The mean coverage for all samples was 930.6* (SD
      = 213.8). Among the 381 genes, 173 single nucleotide variations (SNVs)/insertion
      deletions (InDels), 100 copy number alterations, and 1 structural variation were
      detected. A total of 72.6% of SNVs in primary tumors were also found in recurrent
      lesions, and 27.2% of SNVs in recurrent tumors had newly occurred. Among
      SNVs/InDels detected only in recurrent lesions, 71% had a low variant allele
      fraction (<10%). Patients were classified into three categories based on the
      mutation patterns after cancer treatment. A significant association between the
      major mutation patterns and clinical outcome was observed. Patients whose
      relapsed tumor had fewer mutations than the diagnostic sample tended to be older,
      had longer progression-free survival, and achieved complete remission after
      relapse. Contrastingly, patients whose genetic profile only had concordant
      mutations without any change had the worst outcome. CONCLUSIONS: We characterized
      genomic changes in recurrent pediatric solid tumors. These findings could help to
      understand the biology of relapsed childhood cancer and to develop personalized
      treatment based on their genetic profile.

PMID- 30216765
TI  - Clinical Validation of Automatable Gaussian Normalized CBV in Brain Tumor
      Analysis: Superior Reproducibility and Slightly Better Association with Survival
      than Current Standard Manual Normal Appearing White Matter Normalization.
AB  - PURPOSE: To validate Gaussian normalized cerebral blood volume (GN-nCBV) by
      association with overall survival (OS) in newly diagnosed glioblastoma patients
      and compare this association with current standard white matter normalized
      cerebral blood volume (WN-nCBV). METHODS: We retrieved spin-echo echo-planar
      dynamic susceptibility contrast MRI acquired after maximal resection and prior to
      radiation therapy between 2006 and 2011 in 51 adult patients (28 male, 23 female;
      age 23-87 years) with newly diagnosed glioblastoma. Software code was developed
      in house to perform Gaussian normalization of CBV to the standard deviation of
      the whole brain CBV. Three expert readers manually selected regions of interest
      in tumor and normal-appearing white matter on CBV maps. Receiver operating
      characteristics (ROC) curves associating nCBV with 15-month OS were calculated
      for both GN-nCBV and WN-nCBV. Reproducibility and interoperator variability were
      compared using within-subject coefficient of variation (wCV) and intraclass
      correlation coefficients (ICCs). RESULTS: GN-nCBV ICC (>=0.82) and wCV (<=21%)
      were superior to WN-nCBV ICC (0.54-0.55) and wCV (>=46%). The area under the ROC
      curve analysis demonstrated both GN-nCBV and WN-nCBV to be good predictors of OS,
      but GN-nCBV was consistently superior, although the difference was not
      statistically significant. CONCLUSION: GN-nCBV has a slightly better association
      with clinical gold standard OS than conventional WM-nCBV in our glioblastoma
      patient cohort. This equivalent or superior validity, combined with the
      advantages of higher reproducibility, lower interoperator variability, and easier
      automation, makes GN-nCBV superior to WM-nCBV for clinical and research use in
      glioma patients. We recommend widespread adoption and incorporation of GN-nCBV
      into commercial dynamic susceptibility contrast processing software.

PMID- 30216766
TI  - Exploring the fMRI based neural correlates of the dot probe task and its
      modulation by sex and body odor.
AB  - The dot probe task implicitly cues attention via emotional information, an effect
      which is especially pronounced for threat-related cues. However, several
      questions remain unexplored. The first one is whether chemosignals like the
      androgen-derivative androstadienone can influence such attentional biases.
      Second, few studies have addressed sex differences regarding attentional biases.
      Finally, the neural correlates of these potential behavioral effects based on
      functional magnetic resonance imaging (fMRI) are not known. In two experiments we
      aimed to answer these questions. A total of 159 healthy individuals (58 oral
      contraceptive-users, 42 luteal women, 59 men) were tested. In experiment 1
      (behavioral study) we examined attentional biases behaviorally, while in
      experiment 2 (fMRI study) the dot probe task was complemented by fMRI. Our
      results provide robust evidence that in healthy participants fearful but not
      angry or happy faces lead to a strong general attentional bias. Elucidating the
      neural basis of this effects points to an early processing advantage in bilateral
      thalamus for valid compared to invalid cued fear. However, this finding was
      limited to those participants with the strongest attentional biases and was not
      linked to behavioral measures. Furthermore, no consistent sex or group
      differences existed neither did the putative human chemosignal androstadienone
      reliably modulate attentional biases or change neural processing.

PMID- 30216767
TI  - Glucocorticoid interactions with the dorsal striatal endocannabinoid system in
      regulating inhibitory avoidance memory.
AB  - The endocannabinoid (eCB) system is highly stress sensitive and known to modulate
      memory formation of emotionally arousing experiences across different
      corticolimbic structures. eCB signaling within these circuits is also essentially
      involved in regulating non-genomically mediated glucocorticoid hormone effects on
      memory. It has long been thought that the dorsal striatum, which plays a major
      role in procedural memory and habit formation, is considerably less impacted by
      stressful experiences; however, recent findings indicate that stress and
      glucocorticoids also affect striatal-dependent memory processes. Yet, to what
      extent eCB signaling within the dorsal striatum may mediate such glucocorticoid
      effects on memory consolidation is currently unknown. Here we show, in male
      Wistar rats, that the cannabinoid agonist WIN55,212-2 administered into the
      dorsal striatum immediately after an inhibitory avoidance training experience
      dose-dependently enhanced 48-h retention performance. Conversely, the cannabinoid
      type 1 receptor (CB1R) antagonist AM251 impaired retention when administered into
      the dorsal striatum after inhibitory avoidance training. Most importantly,
      antagonism of striatal CB1R activity with AM251 completely abolished the effect
      of corticosterone or of the membrane-impermeable ligand corticosterone:BSA
      administered posttraining into the dorsal striatum or injected systemically on
      enhancement of inhibitory avoidance memory. Further, suppression of
      glucocorticoid signaling by systemic injection of the corticosterone-synthesis
      inhibitor metyrapone also impaired the memory-enhancing effect of intra-striatal
      WIN55, 212-2 administration. These findings indicate that the eCB system, in
      close interaction with glucocorticoid signaling, is involved in modulating
      plasticity changes underlying memory consolidation not only in corticolimbic
      structures but also within the dorsal striatum.

PMID- 30216768
TI  - Childhood narcolepsy and autism spectrum disorders: four case reports.
AB  - BACKGROUND: Childhood narcolepsy is associated with various emotional,
      behavioural and cognitive dysfunctions as well as with psychiatric and
      neurodevelopmental disorders: anxiety, depression, attention deficit
      hyperactivity disorder and psychosis. A relationship between these conditions is
      unclear - comorbidity or similar pathophysiological mechanisms can be suggested.
      OBJECTIVE: We reported four children with narcolepsy type 1 (NT1) and autism
      spectrum disorder (ASD) - Asperger syndrome (AS). RESULTS AND CONCLUSION: To the
      best of our knowledge co-occurrence of NT1 and AS has not been described in the
      literature as noted in this report.

PMID- 30216769
TI  - The cost-utility of stepped-care algorithms according to depression guideline
      recommendations - Results of a state-transition model analysis.
AB  - BACKGROUND: Evidence-based clinical guidelines for major depressive disorder
      (MDD) recommend stepped-care strategies for sequencing evidence-based treatments
      conditional on treatment outcomes. This study aims to evaluate the cost
      effectiveness of stepped care as recommended by the multidisciplinary clinical
      guideline vis-a-vis usual care in the Netherlands. METHODS: Guideline-congruent
      care as described in stepped-care algorithms for either mild MDD or moderate and
      severe MDD was compared with usual care in a health-economic state-transition
      simulation model. Incremental costs per QALY gained were estimated over five
      years from a healthcare perspective. RESULTS: For mild MDD, the cost-utility
      analysis showed a 67% likelihood of better health outcomes against lower costs,
      and 33% likelihood of better outcomes against higher costs, implying dominance of
      guideline-congruent stepped care. For moderate and severe MDD, the cost-utility
      analysis indicated a 67% likelihood of health gains at higher costs following the
      stepped-care approach and 33% likelihood of health gains at lower costs, with a
      mean ICER of about ?3,200 per QALY gained. At a willingness to pay threshold of
      ?20,000 per QALY, the stepped-care algorithms for both mild MDD and moderate or
      severe MDD is deemed cost-effective compared to usual care with a greater than
      95% probability. LIMITATIONS: The findings of our decision-analytic modelling are
      limited by the accuracy and availability of the underlying evidence. This hampers
      taking into account all individual differences relevant to optimise treatment to
      individual needs. CONCLUSIONS: It is highly likely that guideline-congruent
      stepped care for MDD is cost-effective compared to usual care. Our findings
      support current guideline recommendations.

PMID- 30216770
TI  - Evolution of China's water footprint and virtual water trade: A global trade
      assessment.
AB  - Water embodied in traded commodities is important for water sustainability
      management. This study provides insight into China's water footprint and virtual
      water trade using three specific water named Green, Blue and Grey. A multi-region
      input-output analysis at national and sectoral analysis levels from the years
      1995 to 2009 is conducted. The evolution and position of China's virtual water
      trade across a global supply chain are explored through cluster analysis. The
      results show that China represented 11.2% of the global water footprint in 1995
      and 13.6% in 2009. The green virtual water is the largest of China's exports and
      imports. In general, China is a net exporter of virtual water during this time
      period. China mainly imports virtual water from the USA, India and Brazil, and
      mainly exports virtual water to the USA, Japan and Germany. The agriculture
      sector and the food sector represent the sectors with both the largest import and
      export virtual water quantities. China's global virtual water trade network has
      been relatively stable from 1995 to 2009. China has especially close
      relationships with the USA, Indonesia, India, Canada, Mexico, Brazil and
      Australia. Trade relations, resource endowment and supply-demand relationships
      may play key roles in China's global virtual water footprint network rather than
      geographical location. Finally, policy implications are proposed for China's long
      term sustainable water management and for global supply chain management in
      general.

PMID- 30216771
TI  - Heat and cold related-mortality in 18 French cities.
AB  - OBJECTIVES: Understanding the dynamics of the temperature-mortality relationship
      is an asset to support public health interventions. We investigated the lag
      structure of the mortality response to cold and warm temperatures in 18 French
      cities between 2000 and 2010. METHODS: A distributed lag non-linear generalized
      model using a quasi-Poisson distribution and controlling for classical
      confounding factors was built in each city. A fitted meta-analytical model
      combined the city-specific models to derive the best linear unbiased prediction
      of the association, and a meta-regression explored the influence of background
      characteristics of the cities. The fraction of mortality attributable to cold and
      heat was estimated with reference to the minimum mortality temperature. RESULTS:
      Between 2000 and 2010, 3.9% [CI 95% 3.2:4.6] of the total mortality was
      attributed to cold, and 1.2% [1.1:1.2] to heat. The immediate increase in
      mortality following high temperatures was partly compensated by a harvesting
      effect when temperatures were below the 99.2 percentiles of the mean temperature
      distributions. DISCUSSION: Cold represents a significant public health burden,
      mostly driven by moderate temperatures (between percentiles 2.5 and 25). The
      population is better adapted to warm temperatures, up to a certain intensity when
      heat becomes an acute environmental health emergency (above percentile 99). The
      rapid increase in mortality risk at very high temperatures percentiles calls for
      an active adaptation in a context of climate change.

PMID- 30216772
TI  - How to protect school children from the neurodevelopmental harms of air pollution
      by interventions in the school environment in the urban context.
AB  - Recently, there has been a flurry of publications assessing the effect of air
      pollution on neurodevelopment. Here we present a summary of the results obtained
      within the BRain dEvelopment and Air polluTion ultrafine particles in scHool
      childrEn (BREATHE) Project, which aimed to evaluate the effects of the exposure
      to traffic related air pollutants in schoolchildren in Barcelona. To this end, we
      comprehensively characterised air quality in 39 urban schools from Barcelona and
      identified the main determinants of children's increased exposure. We propose a
      series of measures to be implemented to improve air quality in schools within the
      urban context and, consequently, minimise the negative effects on children's
      neurodevelopment that we found to be associated with the exposure to air
      pollution. We also aimed to list some of the actions pushed by governments and
      the society (including school managers, parents, and children) that have been
      taking place around Europe for promoting better high quality in the school and
      its surroundings.

PMID- 30216773
TI  - Long-term exposure to wind turbine noise and redemption of antihypertensive
      medication: A nationwide cohort study.
AB  - Noise from wind turbines (WTs) has been reported more annoying than traffic noise
      at similar levels, and concerns have been raised about whether WT noise (WTN) can
      increase risk for cardiovascular disease. We aimed to investigate if long-term
      exposure to WTN increases risk for hypertension, estimated as redemption of
      prescriptions for antihypertensive drugs. We identified all Danish dwellings
      within a radius of 20 WT heights from a WT and 25% randomly selected dwellings
      within 20-40 WT heights radius. Using data on WT type and hourly wind conditions
      at each WT, we estimated hourly outdoor (10-10,000 Hz) and low frequency (LF: 10
      160 Hz) indoor WTN for all dwellings, and aggregated it as long-term nighttime
      running means. From nationwide registries, we identified 535,675 persons age 25
      85 years living in these dwellings for >1 year from 1996 to 2013, of whom 83,729
      fulfilled our case definition of redeeming >=2 prescriptions and >=180 defined
      daily doses of antihypertensive drugs within a year. Data were analyzed using
      Poisson regression according to categories of WTN exposure and adjustment for
      individual and area-level covariates. We found no associations between 5-year
      mean exposure to WTN during night and redemption of antihypertensives, with
      hazard ratios (HR) of 0.91 (95% confidence intervals (CI): 0.78-1.06) for outdoor
      WTN >= 42 dB(A) and of 1.06 (CI: 0.83-1.35) for indoor LF WTN >= 15 dB(A) when
      compared to the reference WTN levels (<24 dB(A) and <5 dB(A), respectively). The
      lack of association was consistent across sub-populations of people living on
      farms, far from major roads and with high validity of the noise estimate. For
      people younger than 65 years we found HRs of 0.81 (95% CI: 0.67-0.98) and 0.94
      (95% CI: 0.68-1.30) for outdoor WTN >= 42 dB(A) and indoor WTN >= 15 dB(A),
      respectively, whereas for people above 65 years the corresponding HRs were 1.17
      (95% CI: 0.90-1.52) and 1.28 (95% CI: 0.87-1.88). In conclusion, the present
      study does not support an association between WTN and redemption of
      antihypertensive medication.

PMID- 30216774
TI  - Personal exposure to radio-frequency electromagnetic fields in Europe: Is there a
      generation gap?
AB  - BACKGROUND: Exposure to radiofrequency electromagnetic fields (RF-EMF) from
      mobile communication technologies is changing rapidly. To characterize sources
      and associated variability, we studied the differences and correlations in
      exposure patterns between children aged 8 to 18 and their parents, over the
      course of the day, by age, by activity pattern, and for different metrics of
      exposure. METHODS: Using portable RF-EMF measurement devices, we collected
      simultaneous real-time personal measurements of RF-EMF over 24 to 72 h in 294
      parent-child pairs from Denmark, the Netherlands, Slovenia, Switzerland, and
      Spain. The devices measured the power flux density (mW/m2) in 16 different
      frequency bands every 4 s, and activity diary Apps kept by the participants were
      used to collect time-activity information in real-time. We analyzed their
      exposures by activity, for the different source constituents of exposure:
      downlink (radiation emitted from mobile phone base stations), uplink
      (transmission from phone to base station), broadcast, DECT (digital enhanced
      cordless telecommunications) and Wi-Fi. We looked at the correlations between
      parents and children overall, during day (06:00-22.00) and night (22:00-06:00)
      and while spending time at home. RESULTS: The mean of time-weighted average
      personal exposures was 0.16 mW/m2 for children and 0.15 mW/m2 for parents, on
      average predominantly originating from downlink sources (47% for children and 45%
      for parents), followed by uplink (18% and 27% respectively) and broadcast (25%
      and 19%). On average, exposure for downlink and uplink were highest during the
      day, and for Wi-Fi and DECT during the evening. Exposure during activities where
      most of the time is spent (home, school and work) was relatively low whereas
      exposure during travel and outside activities was higher. Exposure to uplink
      increased with age among young people, while DECT decreased slightly. Exposure to
      downlink, broadcast, and Wi-Fi showed no obvious trend with age. We found that
      exposure to total RF-EMF is correlated among children and their parents
      (Rspearman = 0.45), especially while at home (0.62) and during the night (0.60).
      Correlations were higher for environmental sources such as downlink (0.57) and
      broadcast (0.62) than for usage-related exposures such as uplink (0.29).
      CONCLUSION: The generation gap between children and their parents is mostly
      evident in uplink exposure, due to more and longer uplink and cordless phone
      calls among parents, and their tendency to spend slightly more time in activities
      with higher environmental RF-EMF exposure, such as travel. Despite these
      differences in personal behavior, exposure to RF-EMF is moderately correlated
      between children and their parents, especially exposures resulting from
      environmental RF-EMF sources.

PMID- 30216775
TI  - Self-rated health and depressive symptoms in older adults: A growth mixture
      modeling approach.
AB  - OBJECTIVE: Self-Rated Health (SRH) and depressive symptoms are important
      indicators of global quality of life in older adults. Prior research suggests
      associations between SRH and depressive symptoms. The current study assessed
      latent groups in levels and trajectories of these two subjective health
      indicators and how the latent groups relate to each other. METHODS: Participants
      from the Australian Longitudinal Study of Aging (N = 2,087, ages 65+) were
      assessed over six waves of data collection, spanning eight years. RESULTS: Growth
      Mixture Models were run for SRH and depressive symptoms, each yielded three
      latent groups with similar patterns: for both SRH and depressive symptoms two
      groups differing in their level with worsening status over time, and a third
      stable, but poorer functioning group. Analysis of the assignment of the latent
      groups revealed a consistent pattern for the majority, but some people were high
      in depression and high in SRH and some were low in depression and low in SRH.
      CONCLUSIONS: SRH and depressive symptoms yielded both three latent groups whose
      combination supported the expected assignment for the majority and an unexpected
      assignment for some people. This may be a result of a protective factor existing
      for one variable but not the other.

PMID- 30216776
TI  - Newcastle disease virus infection triggers HMGB1 release to promote the
      inflammatory response.
AB  - High mobility group box 1 (HMGB1) is a key member of the "danger associated
      molecular patterns" (DAMPs) which plays important roles in systemic inflammation
      and has a pathogenic role in infectious diseases like viral or bacterial
      infections. Newcastle disease virus (NDV) infection is proved to cause intense
      inflammatory responses that result in excessive cellular apoptosis and tissue
      damage, but the function of HMGB1 in NDV-induced cytokine storm has not been
      elucidated. Here, we report that HMGB1 is a significant inflammation factor in
      NDV infection. HMGB1 is widely distributed in chicken tissues, and the secretion
      of it was induced by NDV infection both in DF-1 and A549 cells. Moreover,
      inhibiting the secretion of HMGB1, NDV replication was not significantly reduced,
      but it is involved in NDV-induced NF-kappaB activation and the inflammatory
      response. Further investigation showed that HMGB1 promotes inflammatory cytokine
      production through the RAGR, TLR2, and TLR4 receptors. HMGB1-RAGE interaction
      also takes parts in activation of ERK1/2 and JNK induced by NDV infection.
      Neutralizing HMGB1 in vivo, chicken viability was increased. Pathological changes
      and inflammatory cytokines expression were reduced under NDV infection, which
      further confirmed the pathogenic roles of HMGB1 in inflammatory responses. Thus,
      our findings show that HMGB1 contributes to the inflammatory cytokine storm
      induced by NDV infection, which played a critical role in viral pathogenesis.

PMID- 30216777
TI  - Cheating in the name of others: Offering prosocial justifications promotes
      unethical behavior in young children.
AB  - The current research examined whether young children engage in unethical behavior
      to a greater extent when they have a prosocial justification for doing so.
      Participants (3- and 5-year-olds, N = 240) played a guessing game in which they
      were tempted to cheat to win a prize after promising not to do so. In Study 1,
      children were randomly assigned to either an experimental prosocial condition in
      which they were told that the prize would be given to a child who was unable to
      play the game or a control condition in which they were told that they would get
      to keep the prize for themselves. The 5-year-olds, but not the 3-year-olds, were
      more likely to cheat in the prosocial condition than in the control condition.
      Studies 2a and 2b revealed that older children's tendency to engage in prosocial
      cheating was driven by their concern with signaling to others that they are
      prosocial. These findings suggest that the tendency to act unethically to benefit
      others emerges early in development and that this tendency may reflect children's
      interest in prosocial signaling.

PMID- 30216778
TI  - Metabolic response to elevated CO2 levels in Pinus pinaster Aiton needles in an
      ontogenetic and genotypic-dependent way.
AB  - Global climate changes involve elevated atmospheric [CO2], fostering the carbon
      allocation to tree sink tissues, partitioning it into metabolic pathways. We use
      metabolomics analysis in adult and juvenile needles of four Pinus pinaster
      genotypes exposed to two levels of growth [CO2]: ambient (400 MUmol mol-1) and
      enriched (800 MUmol mol-1), to know if the metabolic responses are genotype
      dependent and vary according to the stage of needle ontogeny. The eCO2-induced
      changes in the needle metabolomes are more significant in secondary metabolism
      pathways and especially meaningful in juvenile needles. The heteroblasty has
      important consequences in the expression of the metabolome, and on the plasticity
      to CO2, determining the level of specific metabolite accumulation, showing an
      interdependence between adult and juvenile needles. The P. pinaster needle
      metabolomes also show clear quantitative differences linked to genotype, as well
      as regarding the metabolic response to eCO2, showing both, common and genotype
      specific biochemical responses. Thus, the changes in flavonol levels are mainly
      genotype-independent, while those in terpenoid and free fatty acids are mainly
      genotype-dependent, ratifying the importance of genotype to determine the
      metabolic response to eCO2. To understand the adaptation mechanisms that tree
      species can develop to cope with eCO2 it is necessary to know the genetically
      distinct responses within a species to recognize the CO2-induced changes from the
      divergent approaches, what can facilitate knowing also the possible interrelation
      of the physiological and metabolic responses. That could explain the
      controversial effects of eCO2 on the carbon-based metabolite in conifers, at the
      inter- and intra-specific level.

PMID- 30216779
TI  - Heat priming effects on anthesis heat stress in wheat cultivars (Triticum
      aestivum L.) with contrasting tolerance to heat stress.
AB  - The incidence of heat episodes during the phase of reproductive development in
      crops is accountable for great yield losses worldwide. Plants subjected to stress
      events during vegetative stages (primed) are reported be more resistant to future
      stress exposure during the reproductive phases. We aimed to test if repeated
      early abiotic stresses could improve heat tolerance during anthesis in wheat
      cultivars. Two wheat cultivars (Triticum aestivum L.), 'Gladius' and 'Paragon',
      were subjected to a heat priming process consisting of two periods with heat at
      the developmental stages of three and five completely developed leaves,
      respectively. The primed and non-primed plants were later subjected to either a
      heat stress or non-heat stress (control) temperature for seven days during
      anthesis. Gas exchange and chlorophyll fluorescence were used to investigate the
      physiological performance of the plants. No difference in assimilation rate was
      observed between treatments for 'Gladius'. Measurements were not possible to
      obtain for heat stressed 'Paragon' plants due to premature senescence. We did not
      observe strong evidence to prove our hypothesis of early heat stress (priming)
      being accountable for improving heat tolerance. However, a significant difference
      between cultivars in response to heat stress was observed. The yield parameters
      of 'Gladius' primed plants did not differ from their respectively control
      treatment. A distinct result was observed for the heat sensitive cultivar
      'Paragon', suggesting a cumulative deleterious effect caused by the repeated heat
      stress.

PMID- 30216780
TI  - Synaptic encoding of fear memories in the amygdala.
AB  - Over the years Pavlovian fear conditioning has proved to be a powerful model to
      investigate the neural underpinnings of aversive associative memory formation.
      Although it is well appreciated that plasticity occurring at excitatory synapses
      within the basolateral complex of the amygdala (BLA) plays a critical role in
      associative memory formation, recent evidence suggests that plasticity within the
      amygdala is more distributed than previously appreciated. In particular, studies
      demonstrate that plasticity in the central nucleus (CeA) is critical for the
      acquisition of conditioned fear. In addition, a variety of interneuron
      populations within the amygdala, defined by unique neurochemical markers,
      contribute to distinct aspects of stimulus processing and memory formation during
      fear conditioning. Here, we will review and summarize recent advances in our
      understanding of amygdala networks and how unique players within this network
      contribute to synaptic plasticity associated with the acquisition of conditioned
      fear.

PMID- 30216781
TI  - Lamb waves and electro-mechanical impedance based damage detection using a mobile
      PZT transducer set.
AB  - Lamb waves and electro-mechanical impedance (EMI) based methods are increasingly
      used in damage detection owing to their high sensitivity to small structural
      defects. Lamb wave based methods are effective in detecting damages in a large
      area and electro-impedance based methods are suitable for characterizing the
      identified damage. Based on these two methods, a novel combined damage detection
      method is presented in this research. To achieve this, first, a mobile transducer
      set is developed, which can be used for both the Lamb waves and EMI based
      methods. Then, a baseline-free damage detection strategy that combines the Lamb
      waves and EMI methods is presented. Finally, a laboratory-sized test piece is
      used to validate the effectiveness of the proposed approach. The results achieved
      with the application of the presented combined method for characterizing an L
      shape crack in an aluminum plate show better location accuracy and detection
      efficiency than those obtained by applying only one method.

PMID- 30216782
TI  - Designing a tunable acoustic resonator based on defect modes, stimulated by
      selectively biased PZT rods in a 2D phononic crystal.
AB  - Reconfigurable phononic crystals (PnCs) and related devices are highly attractive
      because of their flexibility for different applications. We present the design
      procedure for a tunable acoustic resonator based on a 2D PnC, consisting of a
      periodic array of piezoelectric rods of radii 175 MUm as inclusions arranged in
      air background. A single point defect devised by a rod of radius 161 MUm,
      replacing one of the inclusions, plays the role of the acoustic resonator,
      leading to a defect frequency in the phononic band gap (fd ~ 432 kHz). Applying a
      ~1% strain to the defect rod, via an external voltage, tunes the defect resonant
      frequency within the phononic band gap. It is shown that the maximum tunability
      and the frequency shift depends on the defect size, and is achieved about Deltafd
      = 440 Hz for the defect with the expense of descending quality factor.
      Considering the pattern of the localized pressure field, we introduce a multi
      defect structure with five symmetric defect rods, corresponding to the maxima of
      field distribution. It is shown that maximum frequency shift of the dominant
      defect frequency is achieved about Deltafd = 1.14 kHz for defect radius of 161
      MUm, when all five defect rods are strained. The proposed tunable filter based on
      multi-defect structure results in an enhancement of about 2.6 times in the
      maximum frequency shift, in comparison with the single defect structure, and
      introduces a promising approach for realizing tunable acoustic devices.

PMID- 30216783
TI  - Patterns of upper limb muscle activation in children with unilateral spastic
      cerebral palsy: Variability and detection of deviations.
AB  - BACKGROUND: The aim of this study was two-fold: (1) to quantify the variability
      of upper limb electromyographic patterns during elbow movements in typically
      developing children and children with unilateral spastic cerebral palsy, and to
      compare different amplitude normalization methods; (2) to develop a method using
      this variability to detect (a) deviations in the patterns of a child with
      unilateral spastic cerebral palsy from the average patterns of typically
      developing children, and (b) changes after treatment to reduce muscle activation.
      METHODS: Twelve typically developing children ([6.7-15.9yo]; mean 11.0 SD 3.0yo)
      and six children with unilateral spastic cerebral palsy ([7.9-17.4yo]; mean 12.4
      SD 4.0yo) attended two sessions during which they performed elbow extension
      flexion and pronation-supination movements. Surface electromyography of the
      biceps, triceps, brachioradialis, pronator teres, pronator quadratus, and
      brachialis muscles was recorded. The Likelihood method was used to estimate the
      inter-trial, inter-session, and inter-subject variability of the electromyography
      patterns for each time point in the movement cycle. Deviations in muscle patterns
      from the patterns of typically developing children and changes following
      treatment were evaluated in a case study of a child with cerebral palsy.
      FINDINGS: Normalization of electromyographic amplitude by the mean peak yielded
      the lowest variability. The variability data were then used in the case study.
      This method detected higher levels of activation in specific muscles compared
      with typically developing children, and a reduction in muscle activation after
      botulinum toxin A injections. INTERPRETATION: Upper limb surface electromyography
      pattern analysis can be used for clinical applications in children with cerebral
      palsy.

PMID- 30216784
TI  - Age and falls history effects on antagonist leg muscle coactivation during
      walking with balance perturbations.
AB  - BACKGROUND: Inspired by a reliance on visual feedback for movement control in
      older age, optical flow perturbations provide a unique opportunity to study the
      neuromuscular mechanisms involved in walking balance control, including aging and
      falls history effects on the response to environmental balance challenges.
      Specifically, antagonist leg muscle coactivation, which increases with age during
      walking, is considered a neuromuscular defense against age-associated deficits in
      balance control. The purpose of this study was to investigate the effects of age
      and falls history on antagonist leg muscle coactivation during walking with and
      without optical flow perturbations of different amplitudes. METHODS: Eleven young
      adults [mean (standard deviation) age: 24.8 (4.8) years], eleven older non
      fallers [75.3 (5.4) years] and eleven older fallers [age: 78 (7.6) years]
      participated in this study. Participants completed 2-minute walking trials while
      watching a speed-matched virtual hallway that, in some conditions, included
      mediolateral optical flow perturbations designed to elicit the visual perception
      of imbalance. FINDINGS: We first found that lower leg antagonist muscle
      coactivation during normal walking increased with age, independent of falls
      history. We also found that older but not young adults increased antagonist leg
      muscle coactivation in the presence of optical flow perturbations, with more
      pervasive effects in older adults with a history of falls. INTERPRETATION: Our
      findings allude to a greater susceptibility to optical flow perturbations in
      older fallers during walking, which points to a higher potential for risk of
      instability in more complex and dynamic everyday environments. These findings may
      also have broader impacts related to the design of innovative training paradigms
      and neuromuscular targets for falls prevention.

PMID- 30216785
TI  - Enhanced anthocyanin accumulation confers increased growth performance in plants
      under low nitrate and high salt stress conditions owing to active modulation of
      nitrate metabolism.
AB  - Plants require nitrogen (N) for growth and development. However, they are
      frequently exposed to conditions of nitrogen deficiency. In addition, anthocyanin
      accumulation is induced under salt stress and nitrate deficiency. To date, most
      studies have revealed that nitrate deficiency under high sucrose levels induce
      high levels of anthocyanin accumulation in plants. However, the underlying
      mechanisms remain unclear. Under nitrate-starved conditions, plant growth rapidly
      worsens and cells eventually die. In addition, plants are severely affected by
      salt exposure. Therefore, in this study, we determined whether increased levels
      of anthocyanin could improve plant growth under salt stress and nitrate-starved
      conditions. We used PAP1-D/fls1ko and ttg1 plants which have a perturbed
      anthocyanin biosynthesis pathway to explore the role of anthocyanin in plant
      adaptation to nitrate-deficient conditions and salt stress. Our results
      demonstrate that high anthocyanin accumulation in PAP1-D/fls1ko plants confers
      enhanced tolerance to nitrate-deficient conditions combined with high salinity.
      PAP1-D/fls1ko plants appeared to use absorbed nitrate efficiently during the
      nitrate reduction process. In addition, nitrate-related genes such as NRT1.1,
      NiA1 and NiA2 were upregulated in the PAP1-D/fls1ko plants. On the basis of these
      findings, it can be concluded that high anthocyanin accumulation helps plants to
      cope with salt stress under nitrate-deficient conditions via the effective
      utilization of nitrate metabolism.

PMID- 30216786
TI  - The role of E2F1-topoIIbeta signaling in regulation of cell cycle exit and
      neuronal differentiation of human SH-SY5Y cells.
AB  - This study aims to test the role of E2F1-topoIIbeta signaling in neuronal
      differentiation of SH-SY5Y cells. With retinoic acid (RA) induction, a high
      percentage of cells were found to be arrested at the G0/G1 phase, with decreased
      levels of cyclinD1, CDK4, phosphorylation status of pRb and E2F1, in addition to
      an elevated level of p27. The cells were shown to differentiate into neuronal
      phenotypes characterized by highly expressed neuronal markers, MAP2 and enriched
      topoIIbeta, and remarkable neurite outgrowth. Exogenously forced E2F1 expression
      with a specific E2F1 plasmid led to suppression of topoIIbeta expression and
      disruption of the neuronal differentiation of SH-SY5Y cells. On further
      examination using the ChIP assay, we found that E2F1 bound directly to the
      promoter region of topoIIbeta, and its binding ability was inversely correlated
      with topoIIbeta expression in response to RA induction. Thus, our findings
      suggest that E2F1-topoIIbeta signaling may play a role in regulation of cell
      cycle exit and neuronal differentiation.

PMID- 30216787
TI  - Second generation atypical antipsychotics olanzapine and aripiprazole reduce
      expression and secretion of inflammatory cytokines in human immune cells.
AB  - Schizophrenia and major depression are associated with alterations in peripheral
      inflammatory markers, and anti-inflammatory therapy has been proposed as a
      promising add-on approach in the pharmacologic treatment of both disorders.
      Second-generation atypical antipsychotics are currently first-line drugs in the
      treatment of schizophrenia and are also used as augmentation strategies in
      treatment-resistant major depression. Furthermore, these drugs have been reported
      to exhibit distinct metabolic side effects and to influence inflammatory
      processes. In this study, we used ex vivo stimulation of primary human peripheral
      blood mononuclear cells (PBMC) from healthy blood donors with atypical
      antipsychotics olanzapine or aripiprazole to examine effects on cytokine
      production independent from metabolic side effects and disease status. Both
      olanzapine and aripiprazole stimulation decreased mRNA levels of IL-1beta, IL-6,
      and TNF-alpha and resulted in diminished protein concentrations of IL-6 and TNF
      alpha in conditioned medium of stimulated PBMC. A multiplex approach revealed
      additional downregulation of IL-2; MIP-1beta and IP-10 secretion. Similarly,
      olanzapine and aripiprazole stimulation of the human monocytic cell line THP-1
      resulted in a significant decrease in expression and secretion of IL-1beta and
      TNF-alpha. Our results suggest that atypical antipsychotics directly influence
      immune cell function and thereby highlight the importance to factor in potential
      side effects of drugs routinely used in treatment of schizophrenia and major
      depression on inflammatory processes when considering anti-inflammatory drug
      therapy as an additional treatment option.

PMID- 30216788
TI  - Regulation of proto-oncogene Orai3 by miR18a/b and miR34a.
AB  - Store Operated Ca2+ Entry (SOCE) mediated by Orai channels is a ubiquitous Ca2+
      influx pathway that regulates several cellular functions. We have earlier
      reported that Orai3, the mammalian specific Orai1 homolog, plays a critical role
      in breast cancer progression. More recently, Orai3 was demonstrated to regulate
      prostate and lung tumorigenesis. Although the tumorigenic potential of Orai3 is
      associated with increase in its expression, the molecular machinery regulating
      its expression remains largely unexplored. Here, by performing extensive
      bioinformatics analysis and functional studies, we identify and characterize
      micro-RNAs (miRNAs) that regulate Orai3 expression and function. We demonstrate
      that miR18a and miR18b positively regulate Orai3 whereas miR34a represses Orai3
      expression and function. All these miRs exert their effect on Orai3 by virtue of
      their direct action on Orai3 3'UTR. These miRs provide novel opportunities for
      targeting Orai3 for better management of cancer. This study further opens up the
      possibility of targeting specific Orai homologs by different miRs in tissue and
      disease specific context.

PMID- 30216789
TI  - Fast simultaneous determination of main components and impurity sodium ion in
      PAMA injection by mixed-mode chromatography.
AB  - This study describes an analytical method to control the quality of potassium
      aspartate and magnesium aspartate (PAMA) injection based on the simultaneous
      detection of the main components (K+, Mg2+ and Asp) and impurities (Na+) using a
      mixed-mode chromatography coupled with charged aerosol detector. To obtain
      optimal chromatographic separation, the effects of organic content, column
      temperature, buffer types, pH and concentrations were evaluated. A Response
      Surface Methodology (RSM) optimal design was performed after single factor
      experiment. The mixed-mode HPLC method is proved to be a complementary approach
      to the conventional ion chromatography (IC). The optimized method was
      successfully validated and applied to the analysis of Asp, K+, Na+ and Mg2+ in
      PAMA injection with good specificity, linearity, accuracy, and repeatability. The
      method would be useful for quality control in PAMA injection and other similar
      drugs, which can provide references for the analysis of drug quality by
      enterprises and drug regulatory department.

PMID- 30216791
TI  - Chemical, biological and molecular modelling analyses to probe into the
      pharmacological potential of Antidesma madagascariense Lam.: A multifunctional
      agent for developing novel therapeutic formulations.
AB  - Antidesma madagascariense Lam. (AM), an indigenous medicinal plant to the
      Mascarene Islands, is used for the treatment of several diseases. We endeavoured
      to validate its use via evaluating the kinetics of inhibition of crude aqueous
      extract (CAE) and crude methanol extract (CME) of AM against key metabolic
      enzymes (pancreatic lipase, cholesterol esterase [CEase], acetylcholinesterase
      [AChE], and urease). In vitro antiglycation, antioxidant, cytotoxicity using
      iCELLigence real time cell analysis system and WST-1 methods, were used. LC-ESI
      MS/MS was employed to determine the phenolic composition of the extracts and
      interaction of selected compounds to the studied enzymes was determined using in
      silico docking. AChE was inhibited by the CME of AM and CEase by the CAE. Both
      extracts were active inhibitors of urease and pancreatic lipase. Hyperoside
      (271.97 MUg/g extract), present in large amount in the CME, docked to the
      enzymatic pocket of urease and CEase. The extracts showed competitive and mixed
      inhibition of urease and pancreatic lipase, respectively. The antioxidant
      capacity of the CME (6.61 MUg GAE/mg crude extract) was higher compared to CAE
      (2.20 MUg GAE/mg crude extract). AM extracts were significantly (p <  0.05) less
      potent than aminoguanidine in preventing advanced glycation end products
      formation. Toxicological screening revealed that both extracts were non-toxic on
      HEK-293 cells. AM crude extracts at concentrations ranging from 78 to 312 MUg/ml
      did not cause a visible change in cell morphology compared to control. This study
      supports the safe use of AM as a biomedicine for the management and/or treatment
      of common non-communicable diseases.

PMID- 30216792
TI  - Comprehensive quality assessment for Rhizoma Coptidis based on quantitative and
      qualitative metabolic profiles using high performance liquid chromatography,
      Fourier transform near-infrared and Fourier transform mid-infrared combined with
      multivariate statistical analysis.
AB  - Rhizoma Coptidis (RC) originated from the dried rhizomes of Coptis herbal species
      is a widely used traditional Chinese medicine in history. In this study, a
      comprehensive quality assessment for RC medicines from C. chinensis, C.
      deltoidea, C. omeiensis and C. teeta species was performed based on quantitative
      and qualitative metabolic profiles obtained from high performance liquid
      chromatography (HPLC), Fourier transform near-infrared (FT-NIR) and Fourier
      transform mid-infrared (FT-MIR) combined with multivariate statistical analysis.
      Eight alkaloids including magnoflorine, groenlandicine, jatrorrhizine,
      columbamine, epiberberine, coptisine, palmatine and berberine were simultaneously
      identified and determined. Epiberberine, berberine, magnoflorine and
      groenlandicine were identified as possible index components. FT-NIR and FT-MIR
      profiles presented the holistic metabolic characterization of RC medicines.
      Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were
      successively performed to clearly illustrate the metabolic variation and
      taxonomic relationship among four RC medicines. Additionally, taking berberine as
      an example, spectral quantification potential was investigated by referring HPLC
      data, using a conventional partial least squares regression (PLSR) algorithm.
      Data fusion strategy exhibited a better prediction for this compound than a
      single technique. Summary, these techniques can complement each other and provide
      a comprehensive and effective quality assessment for RC originated from different
      Coptis plants.

PMID- 30216790
TI  - First inter-laboratory study of a Supercritical Fluid Chromatography method for
      the determination of pharmaceutical impurities.
AB  - Supercritical Fluid Chromatography (SFC) has known a strong regain of interest
      for the last 10 years, especially in the field of pharmaceutical analysis.
      Besides the development and validation of the SFC method in one individual
      laboratory, it is also important to demonstrate its applicability and
      transferability to various laboratories around the world. Therefore, an inter
      laboratory study was conducted and published for the first time in SFC, to assess
      method reproducibility, and evaluate whether this chromatographic technique could
      become a reference method for quality control (QC) laboratories. This study
      involved 19 participating laboratories from 4 continents and 9 different
      countries. It included 5 academic groups, 3 demonstration laboratories at
      analytical instrument companies, 10 pharmaceutical companies and 1 food company.
      In the initial analysis of the study results, consistencies within- and between
      laboratories were deeply examined. In the subsequent analysis, the method
      reproducibility was estimated taking into account variances in replicates,
      between-days and between-laboratories. The results obtained were compared with
      the literature values for liquid chromatography (LC) in the context of impurities
      determination. Repeatability and reproducibility variances were found to be
      similar or better than those described for LC methods, and highlighted the
      adequacy of the SFC method for QC analyses. The results demonstrated the
      excellent and robust quantitative performance of SFC. Consequently, this
      complementary technique is recognized on equal merit to other chromatographic
      techniques.

PMID- 30216793
TI  - Quantification of isoflavone glycosides and aglycones in rat plasma by LC-MS/MS:
      Troubleshooting of interference from food and its application to pharmacokinetic
      study of Semen Sojae Praeparatum extract.
AB  - The isoflavones widely exist in the daily diets and interferences are usually
      inevitable in the determination of the in vivo level of the same analytes. A new
      strategy to eliminate the dietary interference was established to evaluate the
      exposure of isoflavones including daidzin, glycitin, genistin, daidzein,
      glycitein, and genistein in rats fed with Semen Sojae Praeparatum (SSP) extract.
      Plasma samples were pretreated by liquid-liquid extraction with ethyl acetate
      using quercetin as the internal standard (IS). The chromatographic separation was
      achieved on a Symmetry C18 column (100 mm * 3.0 mm) using a gradient mobile phase
      consisting of acetonitril and water (containing 0.1% formic acid) with a run time
      of 13.0 min at a flow rate of 0.4ml/min. The detection was carried out by a
      triple-quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM)
      mode via polarity switching between negative (for and positive (for daidzin
      glycitin) ionization mode. All calibration curves exhibited good linearity (r>
      0.99) over a wide concentration range for all components. The lower limit of
      quantitation (LLOQ) was in the range of 0.1-0.4 ng/ml. The intra-day and inter
      day precisions (RSD) at three different levels were both less than 14.9% and the
      accuracies (RE) ranged from -9.3% to 14.5%. The extraction recoveries of the
      analytes and the IS ranged from 85.7% to 100.2%. The validated method was first
      successfully applied to pharmacokinetic study of the six isoflavones in rat
      plasma after oral administration of SSP extract. The dynamic baseline levels of
      six isoflavones in blank plasma from rats consuming food containing dietary
      isoflavones were measured for the correction of the plasma concentrations. The
      principle pharmacokinetic parameters were calculated from rats with or without
      regular commercial food, and found to be altered by the dietary food containing
      some isoflavones.

PMID- 30216794
TI  - Determination of xanthones and flavonoids of methanol extracts obtained from
      different parts of the plants of three Gentianaceae species.
AB  - Gentianopsis barbata, Halenia corniculata, and Gentianella acuta were widely
      distributed throughout China and commonly used in traditional Chinese medicine.
      However, owing to similar living environments and morphological features, locals
      often had trouble distinguishing between these three species. In this present
      study, chromatograms at 350 nm were obtained and the composition and content of
      their chemical compounds determined using HPLC-DAD/ESI-MS2. In total, 35 chemical
      compounds were detected, 32 of which were identified, 25 of which were xanthones,
      6 flavonoids, and 1 chlorogenic acid. The 350 nm chromatograms of these three
      species displayed evident differences. The individual compounds and their
      occurrence and content in different parts of the plant within different species
      were included in our results. This basic data will be useful for future
      pharmacological study. The total compositions of flavonoids and xanthones were
      approximately comparable in G. barbata and H. corniculata. Meanwhile, xanthones
      were predominant in G. acuta. From the perspective of chemical compound
      compositions, the leaf is recommended as the most valuable medicinal section for
      each of these three species.

PMID- 30216795
TI  - New levels of high angular resolution EBSD performance via inverse compositional
      Gauss-Newton based digital image correlation.
AB  - Conventional high angular resolution electron backscatter diffraction (HREBSD)
      uses cross-correlation to track features between diffraction patterns, which are
      then related to the relative elastic strain and misorientation between the
      diffracting volumes of material. This paper adapts inverse compositional Gauss
      Newton (ICGN) digital image correlation (DIC) to be compatible with HREBSD. ICGN
      based works by efficiently tracking not just the shift in features, but also the
      change in their shape. Modeling a shape change as well as a shift results in
      greater accuracy. This method, ICGN-based HREBSD, is applied to a simulated data
      set, and its performance is compared to conventional cross-correlation HREBSD,
      and cross-correlation HREBSD with remapping. ICGN-based HREBSD is shown to have
      about half the strain error of the best cross-correlation method with a
      comparable computation time.

PMID- 30216796
TI  - Advanced detector signal acquisition and electron beam scanning for high
      resolution SEM imaging.
AB  - The advancement of materials science at the mesoscale requires improvements in
      both sampling volumes/areas and spatial resolution in order to make statistically
      significant measurements of microstructures that influence higher-order material
      properties, such as fatigue and fracture. Therefore, SEM-based techniques have
      become desirable due to improvements in imaging resolution, large sample handling
      capability, and flexibility for in-situ instrumentation. By using fast sampling
      of SEM electron detector signals, intrinsic beam scanning defects have been
      identified that are related to the response time of the SEM electron beam
      deflectors and electron detectors. Mitigation of these beam scanning defects
      using detector sampling approaches and an adaptive model for settling time is
      shown to produce higher resolution SEM images, at faster image acquisition times,
      with a means to quantify the different response functions for various beam
      deflectors and detectors including those for electrons and ions.

PMID- 30216797
TI  - Molecules derived from tRNA and snoRNA: Entering the degradome pool.
AB  - Molecules built of RNA have been the subjects of numerous studies, which have
      made known new functions and structures that these molecules can create. In
      recent years, thanks to next-generation sequencing, it is possible to observe
      very small RNAs and the number of newly discovered RNA molecules is rapidly
      increasing. Among other small oligonucleotides, structures derived from tRNA and
      snoRNA molecules have been observed, and these molecules were determined to not
      be precursors of known RNA molecules. These structures have attracted the
      attention of researchers because the level of accumulation of tRNA or snoRNA
      fragments was relatively high. Additionally, other parts of the parent molecules
      were absent. Derivatives of well-known RNA molecules also have functions that are
      different from their parent molecules. They are mainly involved in regulating the
      expression of genetic information in a similar way to miRNA. In addition, some of
      the miRNAs that have been described are derivatives of tRNA or snoRNA. Most of
      the research on these newly discovered molecules is based on their detection and
      on the study of the macro effects that they exert, in the absence of a
      description of the molecular mechanism by which they arise and work.

PMID- 30216799
TI  - SRT1720 ameliorates sodium taurocholate-induced severe acute pancreatitis in rats
      by suppressing NF-kappaB signalling.
AB  - Severe acute pancreatitis (SAP) is a medical emergency that is often associated
      with multiple organ failure and high mortality. Although an SAP diagnosis
      requires prompt treatment, therapeutic options remain limited. SRT1720 is a newly
      formulatedSIRT1 activator that exerts multiple pharmacological activities with
      beneficial health effects. However, its potential as an SAP treatment has not
      been explored. The current study assessed the effect of SRT1720 on a rat model of
      sodium taurocholate-induced SAP and explored the underlying mechanism. SAP was
      induced in rats by retrograde injection of a 3.5% sodium taurocholate solution (1
      ml/kg) in the biliopancreatic duct. SRT1720 (5 mg/kg) was administered
      intraperitoneally after sodium taurocholate exposure. Serum samples were analysed
      for inflammatory cytokine levels and select enzymatic activities using the enzyme
      linked immunosorbent assay and commercial enzyme activity assay kits,
      respectively; protein expression levels were evaluated by western blotting; mRNA
      levels of biomarkers were determined by quantitative real-time PCR;
      histopathological changes were analysed by haematoxylin and eosin staining and
      immunohistochemistry.SRT1720 treatment significantly reduced serum amylase,
      lipase, pancreatic histological scores, proinflammatory cytokine (TNF-alpha and
      IL-6) levels, and expression of NF-kappaB and p65 in sodium taurocholate-induced
      SAP rats. Importantly, the treatment stimulated SIRT1 and IkappaBalpha levels in
      pancreatic tissue. Our data suggest that SRT1720 protects rats from sodium
      taurocholate-induced SAP by suppressing the NF-kappaB signalling pathway.

PMID- 30216798
TI  - Bortezomib inhibited the progression of diffuse large B-cell lymphoma via
      targeting miR-198.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin
      lymphoma, which is an aggressive malignancy with high variance of clinical
      features and response to the treatment. The proteasome inhibitor bortezomib (BTZ)
      has been demonstrated to suppress the progression of DLBCL, however, the
      underlying molecular mechanisms by which BTZ regulates the growth of DLBCL cells
      remain largely unknown. Increasing evidence has suggested that microRNAs (miRNAs)
      are novel targets of anti-cancer drugs to modulate the progression of cancers.
      Here, we showed BTZ treatment significantly inhibited the proliferation of DLBCL
      CRL-2630 cells. Mechanistically, exposure of BTZ up-regulated the expression of
      miR-198 in DLBCL cells. Depletion of miR-198 significantly reversed the
      inhibitory effect of BTZ on the proliferation of CRL-2630 cells. To further
      characterize the involvement of miR-198 in BTZ-induced growth defects of CRL-2630
      cells, the downstream targets of miR-198 were predicted with the bioinformatics
      tools. The results showed that miR-198 bound the 3'-untranslated region (UTR) of
      the high mobility group AT-hook 1 (HMGA1) and suppressed the expression of HMGA1
      in DLBCL cells. Consistently, BTZ treatment decreased the level of HMAG1 and
      inhibited the migration of DLBCL cells. Our results provided the possible
      mechanism by which BTZ suppressed the growth of DLBCL cells.

PMID- 30216800
TI  - Letter to the editor regarding the article by Chen et al. entitled "Protective
      effects of echinacoside against anoxia/reperfusion injury in H9c2 cells via up
      regulating p-AKT and SLC8A3".

PMID- 30216801
TI  - The impact of proton pump inhibitors on the pharmacokinetics of voriconazole in
      vitro and in vivo.
AB  - Voriconazole (VRC) and proton pump inhibitors (PPIs) have similar metabolic
      pathways. The objectives of the study are to evaluate the impact of PPIs on the
      pharmacokinetics of VRC. Human liver microsomes model was applied to assess the
      inhibitory effects of PPIs on the metabolism of VRC in vitro. A retrospective
      study was also carried out to explore the relationship between the plasma VRC
      trough concentrations and PPIs uses. Patients were divided into six groups:
      control (n = 166), lansoprazole (LAN, n = 38), esomeprazole (ESO, n = 19),
      omeprazole (OME, n = 45), pantoprazole (PAN, n = 43), and ilaprazole (ILA, n =
      38) groups. All five PPIs showed concentration-dependent inhibitory effects on
      the VRC metabolism in human liver microsomes, among which LAN, OME and ESO were
      three of the most potent inhibitors. Consistently, co-administered with LAN, OME
      and ESO significantly increased the plasma VRC trough levels (p <  0.05), whereas
      there was no significant association between VRC concentrations and PAN or ILA
      use. Interestingly, patients in the PPIs groups were more likely to reach the
      therapeutic VRC range of 1-5.5 MUg/mL in steady state when compared with control
      patients (75-81% VS 69%). In conclusion, although all PPIs showed inhibitory
      effects on the VRC metabolism in vitro, only LAN, OME and ESO significantly
      increased VRC plasma concentrations. This study should be helpful for choice of
      the type of PPIs for patients administered with VRC.

PMID- 30216802
TI  - Chemopreventive and antitumor effects of benzyl isothiocynate on HCC models: A
      possible role of HGF /pAkt/ STAT3 axis and VEGF.
AB  - BACKGROUND: Benzyl isothiocyanate (BITC) is a member of the isothiocyanate
      compounds that found in cruciferous vegetables. BITC has a potential anticancer
      effect in different types of tumors. Few studies referred to the antineoplastic
      effect of BITC against HCC. The mechanism of BITC concerning retardation of HCC
      progression is incompletely understood. AIM OF THE WORK: This study evaluated the
      role of HGF, pAkt and STAT3 in BITC induced HCC growth retardation. METHOD: HCC
      was induced in mice using diethylnitrosamine (DEN) 75 mg/kg once a week for 4
      weeks. BITC 10 and 20 mg/kg was given to mice orally each day for 10 weeks. The
      HCC cell lines HepG2 and Huh-7 were also used to evaluate the effect of BITC on
      tumor cells behavior. Immunoassay was used to detect expressions of caspase-3
      activity, VEGF, MMP-2, TNF-alpha, HGF and pAkt. STAT3 expression was detected in
      liver tissues using immunohistochemical staining. RESULTS: BITC has a potential
      role in suppressing hepatic precancerous lesion progression in mice. The drug
      increased caspase-3 activity in tumor cells and inhibited the angiogenic marker
      VEGF. It also decreased the metastatic marker MMP-2. This anticancer effect of
      BITC was observed in DEN treated mice as well as in hepatoma cell lines. The
      reported antineoplastic activity was correlated with downregulation of HGF and
      its downstream molecules pAkt and STAT3. CONCLUSION: The effect of BITC on HGF
      /pAkt/ STAT3 axis has a potential role in both chemopreventive and
      chemotherapeutic effects of BITC.

PMID- 30216803
TI  - Student perceptions of faculty feedback following medication errors - A
      descriptive study.
AB  - Nursing students make medication errors as they progress through educational
      programs. It is important that faculty feedback is such that students feel
      comfortable reporting subsequent medication errors. The objectives of this study
      are to determine factors which increase the likelihood of nursing students
      reporting medication errors; to elicit nursing student perception of faculty
      feedback following a medication error, and determine how this faculty feedback
      impacts reporting of subsequent medication errors; and to develop recommendations
      regarding the most effective faculty approaches when providing feedback to
      nursing students following medication errors. This quantitative study uses a non
      experimental, descriptive design. A convenience sample of 106 nursing students in
      one Canadian province completed a self-report questionnaire. The factors
      identified as increasing the likelihood of reporting medication errors for
      students who made a medication error were the same as for those who did not make
      an error. Group sizes were too small to determine if characteristics of faculty
      feedback had a significant impact on likelihood of reporting future errors.
      Students in both groups indicated intention to report errors based upon
      professional attitudes, behaviors and/or values. The researchers concluded that
      professional socialization, in combination with supportive learning environments,
      may increase student comfort in reporting medication errors.

PMID- 30216804
TI  - Mental health nursing placement: A comparative study of non-traditional and
      traditional placement.
AB  - Professional placement experiences have been considered as an approach to
      improving nursing attitudes towards mental health nursing and selection of mental
      health nursing as a career. Mental health nursing placements are now occurring in
      less traditional settings, however, published research of these placements
      remains scarce. The aim of this non-experimental comparative study was to
      investigate the impact of nursing student participation in a non-traditional
      placement, compared to participation in traditional placement. Particular focus
      was on the attitudes of nursing students toward mental health nursing and career
      preferences. Participants of the intervention group attended the non-traditional
      placement, (n = 23). Participants of the comparison group attended traditional
      placement settings (n = 27), including placements in inpatient and community
      mental health. The study utilised The Preplacement Survey. Results showed
      significant differences in scores of the non-traditional placement Recovery Camp
      cohort related to reduced anxiety, reduced negative attitudes, and increased
      preparedness for mental health. These correlated with a comparatively increased
      desire to pursue a future career in mental health; albeit not a statistically
      significant increase. Considering mental health care, in any setting, is highly
      dependent on the training and ability of nurses to deliver effective service, the
      findings of the current study are important.

PMID- 30216806
TI  - Smart vaccine delivery based on microneedle arrays decorated with ultra-pH
      responsive copolymers for cancer immunotherapy.
AB  - Despite the tremendous potential of DNA-based cancer vaccines, their efficacious
      delivery to antigen presenting cells to stimulate both humoral and cellular
      response remains a major challenge. Although electroporation-based transfection
      has improved performance, an optimal strategy for safe and pain-free vaccination
      technique remains elusive. Herein, we report a smart DNA vaccine delivery system
      in which nanoengineered DNA vaccine was laden on microneedles (MNs) assembled
      with layer-by-layer coating of ultra-pH-responsive OSM-(PEG-PAEU) and
      immunostimulatory adjuvant poly(I:C), a synthetic double stranded RNA.
      Transcutaneous application of MN patches onto the mice skin perforate the stratum
      corneum with minimal cell damage; subsequent disassembly at the immune-cell-rich
      epidermis/dermis allows the release of adjuvants and DNA vaccines, owing to the
      ultra-sharp pH-responsive nature of OSM-(PEG-PAEU). The released adjuvant and DNA
      vaccine can enhance dendritic cell maturation and induce type I interferons, and
      thereby produce antigen-specific antibody that can achieve the antibody-dependent
      cell-mediated cytotoxicity (ADCC) and CD8+ T cell to kill cancer cells.
      Strikingly, transcutaneous application of smart vaccine formulation in mice
      elicited 3-fold greater frequencies of Anti-OVA IgG1 serum antibody and 3-fold
      excess of cytotoxic CD8+ T cell than soluble DNA vaccine formulation. As a
      consequence, the formulation rejected the murine B16/OVA melanoma tumors in
      C57BL/6 mice through the synergistic activation of antigen-specific ADCC and
      cytotoxic CD8+ T cells. The maneuvered use of vaccine and adjuvant poly(I:C) in
      MNs induces humoral and cellular immunity, which provides a promising vaccine
      technology that shows improved efficacy, compliance, and safety.

PMID- 30216807
TI  - Preconditioning of bone marrow-derived mesenchymal stem cells with N-acetyl-L
      cysteine enhances bone regeneration via reinforced resistance to oxidative
      stress.
AB  - Oxidative stress on transplanted bone marrow-derived mesenchymal stem cells
      (BMSCs) during acute inflammation is a critical issue in cell therapies. N-acetyl
      L cysteine (NAC) promotes the production of a cellular antioxidant molecule,
      glutathione (GSH). The aim of this study was to investigate the effects of pre
      treatment with NAC on the apoptosis resistance and bone regeneration capability
      of BMSCs. Rat femur-derived BMSCs were treated in growth medium with or without 5
      mM NAC for 6 h, followed by exposure to 100 MUM H2O2 for 24 h to induce oxidative
      stress. Pre-treatment with NAC significantly increased intracellular GSH levels
      by up to two fold and prevented H2O2-induced intracellular redox imbalance,
      apoptosis and senescence. When critical-sized rat femur defects were filled with
      a collagen sponge containing fluorescent-labeled autologous BMSCs with or without
      NAC treatment, the number of apoptotic and surviving cells in the transplanted
      site after 3 days was significantly lower and higher in the NAC pre-treated
      group, respectively. By the 5th week, significantly enhanced new bone formation
      was observed in the NAC pre-treated group. These data suggest that pre-treatment
      of BMSCs with NAC before local transplantation enhances bone regeneration via
      reinforced resistance to oxidative stress-induced apoptosis at the transplanted
      site.

PMID- 30216805
TI  - Multivalent biomaterial platform to control the distinct arterial venous
      differentiation of pluripotent stem cells.
AB  - Vascular endothelial cells (ECs) differentiated from pluripotent stem cells have
      enormous potential to be used in a variety of therapeutic areas such as tissue
      engineering of vascular grafts and re-vascularization of ischemic tissues. To
      date, various protocols have been developed to differentiate stem cells toward
      vascular ECs. However, current methods are still not sufficient to drive the
      distinct arterial venous differentiation. Therefore, developing refined method of
      arterial-venous differentiation is critically needed to address this gap. Here,
      we developed a biomaterial platform to mimic multivalent ephrin-B2/EphB4
      signaling and investigated its role in the early arterial and venous
      specification of pluripotent stem cells. Our results show immobilized ephrinB2 or
      EphB4 on hydrogel substrates have a distinct effect on arterial venous
      differentiation by regulating several arterial venous markers. When in
      combination with Wnt pathway agonist or BMP4 signaling, the ephrin-B2/EphB4
      biomaterial platform can create diverging EC progenitor populations,
      demonstrating differential gene expression pattern across a wide range of
      arterial and venous markers, as well as phenotypic markers such as anti
      thrombotic, pro-atherogenic and osteogenic genes, that are consistent with the in
      vivo expression patterns of arterial and venous ECs. Importantly, this distinct
      EC progenitor population cannot be achieved by current methods of applying
      soluble factors or hemodynamic stimuli alone, illustrating that fine-tuning of
      developmental signals using the biomaterial platform offers a new approach to
      better control the arterial venous differentiation of stem cells.

PMID- 30216808
TI  - Pros and cons of using ORBEYETM for microneurosurgery.
AB  - OBJECTIVE: To evaluate the pros and cons of using a newly developed microscope,
      ORBEYETM, during microneurosurgery. PATIENTS AND METHODS: ORBEYETM use in 14
      microneurosurgical procedures was retrospectively assessed by nine neurosurgeons
      after the procedure. A questionnaire comprising 20 questions was designed and
      used for evaluation. RESULTS: Compared with the current gold standard, the
      binocular microscope, ease of setting up the equipment was scored the highest,
      whereas ease of conducting surgery in a position of an assistant was scored the
      lowest. Among characteristics of ORBEYETM itself, the space-saving feature was
      scored the highest and was followed by the ability to perform procedures in a
      comfortable position. The only characteristic that was rated below average was
      ease of operation in a position of an assistant. Neurosurgeons with greater
      experience (more than five procedures using ORBEYETM) provided significantly
      higher scores (p = 0.0196) for characteristics of ORBEYETM itself compared with
      neurosurgeon with fewer ORBEYETM experience. CONCLUSIONS: The main benefits of
      the ORBEYETM are its compact size and freedom from focusing through the eye lens
      of a conventional binocular microscope. However, it appears to be disadvantageous
      for operating in a position of an assistant because the surgical field has a
      rotated view on the monitor from a position of an assistant. Nonetheless, because
      of certain advantages, we believe the ORBEYETM could be of additional help to use
      of conventional binocular microscope at the moment and will facilitate
      microneurosurgery in the future.

PMID- 30216809
TI  - The dose of direct oral anticoagulants and outcomes of intracerebral hemorrhage:
      Preliminary findings.
AB  - OBJECTIVES: The effect of a direct-acting oral anticoagulant (DOAC) dose on
      intracerebral hemorrhage (ICH) severity and outcome remains unclear. The aim of
      this study is to clarify the frequency of off-label dosing of DOAC treatments in
      ICH patients and compare clinical characteristics. PATIENTS AND METHODS: We
      studied 43 patients with ICH who were treated with DOAC for nonvalvular atrial
      fibrillation before the onset of ICH. DOAC treatments were categorized into three
      groups based on the following doses: optimal dose, under-dose, and overdose.
      RESULTS: Overall, 31 patients were optimally dosed, 10 were under-dosed, and 2
      were overdosed. CHADS2 and CHA2DS2-VASc scores were the highest in the overdose
      group (median, 4, 6, respectively) and the lowest in the optimal dose group
      (median, 2, 4, respectively) (p = 0.006, p = 0.005, respectively). ICH severity
      measured using the National Institutes of Health Stroke Scale scores was the
      highest in the overdose group (median, 26.5) and the lowest in the under-dose
      group (median, 6.5) (p = 0.244). Larger initial hematoma volume was observed in
      the overdose group. The ratio of good outcome (modified Rankin Scale score <= 2)
      was higher in the under-dose group (40%) than the other groups, but this
      difference was not significant. CONCLUSION: Our study shows only a few patients
      received overdosing of a DOAC before the onset of ICH, and they were associated
      with poorer functional outcomes. Conversely, under-dosing was associated with
      better functional outcomes than the other groups.

PMID- 30216810
TI  - Montreal Cognitive Assessment score correlates with regional cerebral blood flow
      in post-stroke patients.
AB  - OBJECTIVE: Valid and reliable measures are needed to assess post-stroke cognitive
      impairment. The Montreal Cognitive Assessment (MoCA) has been considered a
      superior screening test to the Mini-Mental State Examination (MMSE) for patients
      with post-stroke cognitive impairment, particularly in executive function, which
      may be related to reduction in regional cerebral blood flow (rCBF). In this
      study, we determined whether MoCA and MMSE scores correlate with rCBF assessed
      with SPECT in the subacute phase after ischemic stroke. PATIENTS AND METHODS: We
      retrospectively enrolled 28 patients who were admitted to the Red Cross Otsu
      Hospital with acute cerebral infarction, which was confirmed by magnetic
      resonance imaging (MRI), if they underwent cognitive assessment (MoCA/MMSE) and
      123I-IMP SPECT imaging within 3 weeks post-stroke during a study period of 5
      months. Correlation analyses between rCBF and MoCA or MMSE scores were performed
      by statistical parametric mapping (SPM) and volume-of-interest (VOI) analyses.
      RESULTS: Total MoCA score correlated with the rCBF in the prefrontal cortex,
      cingulate cortex, caudate nucleus and thalamus by SPM analysis (uncorrected p <
      0.001; cluster-level corrected p < 0.05). Among the subtest scores of MoCA,
      visuoexecutive function, attention, language and delayed recall scores were
      positively correlated with rCBF in the prefrontal cortex by VOI analysis (p <
      0.05). However, total MMSE score did not correlate significantly with any of the
      rCBF measures. CONCLUSIONS: Post-stroke cognitive performance assessed with MoCA
      positively correlated with rCBF in brain regions mainly comprising the prefrontal
      subcortical circuits. The findings of this hypothesis-generating study support
      the notion that MoCA is useful for assessing post-stroke cognitive status.

PMID- 30216811
TI  - Marine microplastic: Preparation of relevant test materials for laboratory
      assessment of ecosystem impacts.
AB  - Studies investigating the effects of plastic litter on marine biota have almost
      exclusively utilised pristine plastic materials that are homogeneous in polymer
      type, size, shape and chemical composition. This is particularly the case for
      microplastics (<5 mm), where collecting sufficient quantities from the marine
      environment for use in laboratory impacts studies is simply not feasible.
      Weathered plastics collected from the marine environment show considerable
      physical and chemical differences to pristine and post-production consumer
      plastics. For this study, macroplastic litter was collected on a Dutch beach and
      cryo-milled to create a microplastic mixture for environmental impact
      assessments. The sample composition followed proportions of marine plastic litter
      types observed in an earlier large beach clean-up. Polymer composition of the
      sample was assessed by infrared spectroscopy (ATR-FTIR) and differential scanning
      calorimetry analysis (DSC). The particle size distribution of the cryo-milled
      microplastics showed that particles 0.5-2.0 mm represented 68% of mass, but
      smaller sizes (<2 mm) strongly dominated numerically. Inductively coupled plasma
      spectroscopy (ICP-MS and ICP-OES) analysis of the microplastic mixture revealed a
      broad range of metals and other elements (e.g. Al, Cd, Cr, Fe, Mg, Pb, S and Zn),
      representing common inorganic additives used as colorants, fillers and
      stabilisers. GC-MS analysis identified a broad range of organic plasticisers,
      stabilisers, antioxidants and flame retardants. Comparison of different
      analytical approaches showed that creation of a homogeneous microplastic mixture
      is possible, representing a first step in closing the gap between laboratory
      studies with pristine materials and realistic scenarios with weathered
      microplastic.

PMID- 30216812
TI  - Fly-ash as a low-cost material for isolation of phosphoproteins.
AB  - Metal oxide affinity chromatography (MOAC) is one of the most commonly used
      techniques for selective isolation phosphoproteins and phosphopeptides. This
      technique is capable of capturing the phosphorylated biomolecules through the
      affinity of the phosphoryl group for metal oxides/hydroxides. Fly-ash (FA), a by
      product of coal-combustion power plants, is primarily composed of oxides of
      silicon and metals, among which iron and titanium. A number of studies have
      demonstrated the potential of these metal oxides for phosphoprotein and
      phosphopeptide enrichment. FA is annually produced over hundred million tons
      worldwide and generally considered as hazardous waste. It is thus of great
      importance to enhance its utilization. Here we present the first demonstration of
      the utility of FA as a low-cost MOAC material for the enrichment of
      phosphoproteins. With an FA-microcolumn, phosphoproteins can be successfully
      sequestered from other proteins. FA-microcolumns are shown to be simple, cheap
      and selective devices for phosphoprotein enrichment from a small volume of
      mixtures.

PMID- 30216813
TI  - 210Po and 210Pb in forest mushrooms of genus Leccinum and topsoil from northern
      Poland and its contribution to the radiation dose.
AB  - Wild growing mushrooms are traditional food items for man and also an important
      source of nutrients for small and big wildlife. Nevertheless, they can be species
      - specifically vulnerable for contamination with heavy metals and radionuclides.
      We studied a less known phenomenon of accumulation of highly toxic, the alpha
      radiation emitter such as 210Po and the beta emitter 210Pb by three Leccinum
      mushrooms: orange oak bolete L. aurantiacum (Bull.) Gray (previous name Leccinum
      aurantiacum var. quercinum Pilat), foxy bolete L. vulpinum Watling and slate
      bolete L. duriusculum (Schulzer ex Kalchbr.) Singer. Fungal and soil materials
      were collected from areas of a different geochemical composition in the northern
      regions of Poland. In parallel evaluated was the risk to human consumer due to
      possible intake of 210Po and 210Pb with a mushroom meal. Results showed a
      heterogeneous distribution of 210Po and 210Pb activity concentrations within caps
      and stipes of fruiting bodies. Overall activity concentration for whole dried
      fungi material ranged from 0.59 +/- 0.38 to 3.2 +/- 0.2 Bq 210Po kg-1 and from
      0.45 +/- 0.04 to 3.1 +/- 0.2 Bq 210Pb kg-1. Evaluation showed that Leccinum
      mushrooms consumed by locals in typical quantity of 0.5 kg (dry biomass) can
      contribute into annual effective radiation dose at 0.90-3.81 MUSv from 210Po
      decay and 0.31-2.14 MUSv from 210Pb decay, which is a small portion of the annual
      effective radiation dose of 210Po and 210Pb for human inhabiting the northern
      regions of Poland.

PMID- 30216814
TI  - Fast degradation of diclofenac by catalytic hydrodechlorination.
AB  - Aqueous-phase catalytic hydrodechlorination (HDC) has been scarcely explored in
      the literature for the removal of chlorinated micropollutants. The aim of this
      work is to prove the feasibility of this technology for the fast and
      environmentally-friendly degradation of such kind of compounds. Diclofenac (DCF),
      a highly consumed anti-inflammatory drug, has been selected as the target
      pollutant given its toxicity and low biodegradability. The commercial Pd/Al2O3
      (1% wt.) catalyst has been used due to its prominent role on this field. Complete
      degradation of DCF was achieved in a short reaction time (20 min) under ambient
      conditions (25  degrees C, 1 atm) at [DCF]0 = 68 MUM; [Pd/Al2O3]0 = 0.5 g L-1 and
      H2 flow rate of 50 N mL min-1. Remarkably, the chlorinated intermediate (2-(2
      chloroanilino)-phenylacetate (Cl-APA)) generated along reaction was completely
      removed at the same time, being the chlorine-free compound 2-anilinophenylacetate
      (APA) the only final product. A reaction scheme based on this consecutive pathway
      and a pseudo-first-order kinetic model have been proposed. An apparent activation
      energy of 43 kJ mol-1 was obtained, a comparable value to those previously
      reported for conventional organochlorinated pollutants. Remarkably, the catalyst
      exhibited a reasonable stability upon three successive uses, achieving the
      complete degradation of the drug and obtaining APA as the final product in 30
      min. The evolution of ecotoxicity was intimately related to the disappearance of
      the chlorinated organic compounds and thus, the final HDC effluents were non
      toxic. The versatility of the system was finally demonstrated in different
      environmentally-relevant matrices (wastewater treatment plant effluent and
      surface water).

PMID- 30216815
TI  - Field evolved resistance to pyrethroids, neonicotinoids and biopesticides in
      Dysdercus koenigii (Hemiptera: Pyrrhocoridae) from Punjab, Pakistan.
AB  - The red cotton bug, Dysdercus koenigii (Fabricius) is an important emerging
      economic pest of cotton, Gossypium hirsutum Linnaeus in Pakistan. Insecticides
      are the primary management tactics to suppress populations of this pest. However,
      resistance to insecticides evolves due to substantial and repeated applications.
      The resistance to pyrethroids, neonicotinoids and biopesticides have been
      evaluated in many pests worldwide, nevertheless lack of information in D.
      koenigii. Therefore, the aforementioned insecticide resistance in five field
      populations of D. koenigii collected from Multan, Makhdoom Rashid, Jahanian,
      Lodhran and Vehari districts of Punjab, Pakistan during 2015-2017 was determined
      by using seed dip method. Based on the present results, D. koenigii has developed
      moderate to very high resistance to acetamiprid (RR = 33-433) and imidacloprid
      (RR = 21-173), low to high resistance to emamectin benzoate (RR = 14-52), and
      very low to high resistance to spinosad (RR = 4.13-54), compared to the
      susceptible population. However, all field populations of D. koenigii remained
      susceptible to deltamethrin (RR = 0.62-2.17) and lambda-cyhalothrin (RR = 0.91
      1.97). A rotational use of pyrethroids with provision of other integrated pest
      management tactics is recommended to manage insecticide resistance in D.
      koenigii.

PMID- 30216816
TI  - Effects of CO2 enrichment on two microalgae species: A toxicity approach using
      consecutive generations.
AB  - As a result of the increasing pressure provoked by anthropogenic activities, the
      world climate is changing and oceans health is in danger. One of the most
      important factors affecting the marine environment is the well-known process
      called ocean acidification. Also, there are other natural or anthropogenic
      processes that produce an enrichment of CO2 in the marine environment (CO2
      leakages from Carbon Capture and Storage technologies (CCS), organic matter
      diagenesis, volcanic vents, etc). Most of the studies related to acidification of
      the marine environment by enrichment of CO2 have been focused on short-term
      experiments. To evaluate the effects related to CO2 enrichment, laboratory-scale
      experiments were performed using the marine microalgae Tetraselmis chuii and
      Phaeodactylum tricornutum. Three different pH values (two treatments - pH 7.4 and
      6.0 - and a control - pH 8.0) were tested on the selected species across four
      consecutive generations. Seawater was collected and exposed to different
      scenarios of CO2 enrichment by means of CO2 injection. The results showed
      different effects depending on the species and the generation used. Effects on T.
      chuii were shown on cell density, chlorophyll-a and metabolic activity, however,
      a slight adaptation across generations was found in this last parameter. P.
      tricornutum was more sensitive to acidification conditions through generations,
      with practically total growth inhibition in the fourth one. The conclusions
      obtained in this work are useful to address the potential ecological risk related
      to acidification by enrichment of CO2 on the marine ecosystem by using
      consecutive generations of microalgae.

PMID- 30216818
TI  - Gallbladder carcinoma and epithelial dysplasia: Appropriate sampling for
      histopathology.
AB  - Gallbladder carcinoma (GC) is an uncommon malignancy with an overall 5-year
      survival of <5%. Due to overlap of clinical presentation with the more common
      cholecystitis, an estimated 50-65% of all GCs are found incidentally. Epithelial
      dysplasia is identified in ~50% of specimens with invasive carcinoma. Recent
      expert panel guidelines have recommended histologic examination of the entire
      gallbladder in cases where initial sampling reveals dysplasia. 89 cases of GC, 34
      high grade dysplasia (HGD), and 60 low grade dysplasia (LGD) were identified in
      cholecystectomy specimens assessed at our institution over the last 15 years. Pre
      operative imaging (either ultrasound or CT) only identified 52% of mass lesions
      in GC cases. Among gallbladder specimens with epithelial dysplasia only at
      initial sampling, additional sectioning was performed in 59% of HGD and 55% of
      LGD. Additional sectioning of gallbladder specimens with HGD had a higher yield
      (10%) for identifying invasive carcinoma than those with LGD (0 of 28). The
      diagnostic yield of additional sectioning is significantly higher in the setting
      of high grade as compared to low grade dysplasia, suggesting that sampling at the
      discretion of the pathologist may be sufficient for the latter.

PMID- 30216817
TI  - Temperature susceptibility of a mesophilic anaerobic membrane bioreactor treating
      saline phenol-containing wastewater.
AB  - This study examined the temperature susceptibility of a continuous-flow lab-scale
      anaerobic membrane bioreactor (AnMBR) to temperature shifts from 35  degrees C to
      55  degrees C and its bioconversion robustness treating synthetic phenolic
      wastewater at 16 gNa+.L-1. During the experiment, the mesophilic reactor was
      subjected to stepwise temperature increases by 5  degrees C. The phenol
      conversion rates of the AnMBR decreased from 3.16 at 35  degrees C to 2.10
      mgPh.gVSS-1.d-1 at 45  degrees C, and further decreased to 1.63 mgPh.gVSS-1.d-1
      at 50  degrees C. At 55  degrees C, phenol conversion rate stabilized at 1.53
      mgPh.gVSS-1.d-1 whereas COD removal efficiency was 38% compared to 95.5% at 45 
      degrees C and 99.8% at 35  degrees C. Interestingly, it was found that the phenol
      degradation process was less susceptible for the upward temperature shifts than
      the methanogenic process. The temperature increase implied twenty-one operational
      taxonomic units from the reactor's microbial community with significant
      differential abundance between mesophilic and thermophilic operation, and eleven
      of them are known to be involved in aromatic compounds degradation. Reaching the
      upper-temperature limits for mesophilic operation was associated with the
      decrease in microbial abundance of the phyla Firmicutes and Proteobacteria, which
      are linked to syntrophic phenol degradation. It was also found that the particle
      size decreased from 89.4 MUm at 35  degrees C to 21.0 MUm at 55  degrees C. The
      accumulation of small particles and higher content of soluble microbial protein
      like substances led to increased transmembrane pressure which negatively affected
      the filtration performance. Our findings indicated that at high salinity a
      mesophilic AnMBR can tolerate a temperature up to 45  degrees C without being
      limited in the phenol conversion capacity.

PMID- 30216819
TI  - Lactococci dominate the bacterial communities of fermented maize, sorghum and
      millet slurries in Zimbabwe.
AB  - Maize, sorghum and millet fermented porridges are important as complementary
      foods for young children in Africa. The objective of the present study was to
      gain some insights into the bacterial communities of fermented slurries prepared
      from maize, sorghum and millets originating from different locations in Zimbabwe,
      and prepared either at household or laboratory level. A deep sequencing approach
      targeting the hypervariable V4 region of the 16S rRNA gene was used and yielded
      about 100,000 sequences per sample. Lactococcus dominated all the fermented
      slurries, flanked by other lactic acid bacteria such as Weissella, Leuconostoc
      and Enterococcus. Enterobacteriaceae detected in the water samples persisted
      throughout all the fermented cereals. Other sub-dominant bacteria identified in
      the fermented slurries included Aeromonas, Pseudomonas and Acinetobacter. In
      addition, some Proteobacteria, Actinobacteria and Bacteroidetes associated with
      the raw materials and environment were also detected. Fermented slurries could
      not be differentiated based on their origin nor on the type of fermentation, but
      clear differences were observed between red sorghum fermented slurries and
      fermented slurries prepared from other cereal flours. A thorough understanding of
      the functional capacities of the microbiota in African fermented slurries is
      highly needed in order to steer the fermentation for the production of standard,
      safe and nutritious fermented products.

PMID- 30216820
TI  - Sleep disturbances and later cognitive status: a multi-centre study.
AB  - OBJECTIVE: To investigate the associations between sleep disturbances in mid-life
      and late-life and late-life cognitive status. METHODS: In four population-based
      studies (three Swedish studies: H70 study, Kungsholmen Project (KP) and The
      Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD); and one
      Finnish study: Cardiovascular Risk Factors, Aging and Dementia (CAIDE)),
      participants provided self-reports on insomnia, nightmares and general sleep
      problems. Late-life cognitive status was measured by the Mini Mental State Exam
      (MMSE). The associations between late-life sleep disturbances and cognition 3-11
      years later were investigated across all studies (n = 3210). Mean baseline ages
      were 70 (CAIDE, H70 and SWEOLD), and 84 years (KP). Additional analyses examined
      the association between midlife sleep and late-life cognition using CAIDE (21 and
      31 years follow-up, n = 1306, mean age 50 years), and SWEOLD (20-24 years follow
      up, n = 2068, mean age 58 years). Ordered logistic regressions, adjusted for
      potential baseline confounders, were used in the analyses. RESULTS: Late-life
      sleep disturbances were associated with poorer cognition after 3-11 years (fully
      adjusted beta = -0.12, 95% CI = -0.24 to -0.01). Midlife nightmares and insomnia
      were also associated with lower MMSE scores (fully adjusted beta = -0.28, 95% CI
      = -0.49 to -0.07 and beta = -0.20, 95% CI = -0.39 to -0.01), although the latter
      association was attenuated after adjusting for lifestyle/health-related
      confounders. Midlife general sleep problems were not associated with late-life
      MMSE performance. CONCLUSIONS: Sleep disturbances and midlife nightmares were
      associated with lower MMSE scores, which suggests that sleep disturbances in
      earlier life stages can be associated with worse late-life cognition.

PMID- 30216821
TI  - Protection of the endothelial glycocalyx by antithrombin in an endotoxin-induced
      rat model of sepsis.
AB  - INTRODUCTION: Injury and loss of the endothelial glycocalyx occur during the
      early phase of sepsis. We previously showed that antithrombin has a protective
      effect on this structure in vitro. Here, we investigated the possible protective
      effects of antithrombin in an animal model of sepsis. METHODS: Wistar rats were
      injected with endotoxin, and circulating levels of syndecan-1, hyaluronan,
      albumin, lactate and other biomarkers were measured in an antithrombin-treated
      group and an untreated control group (n = 6 in each group). Intravital microscopy
      was used to observe leukocyte adhesion, microcirculation, and syndecan-1
      staining. RESULTS: The circulating levels of syndecan-1 and hyaluronan were
      significantly reduced in the antithrombin-treated group, compared with the
      untreated controls. Lactate levels and albumin reduction were significantly
      attenuated in the antithrombin-treated group. Intravital microscopic observation
      revealed that both leukocyte adhesion and blood flow were better maintained in
      the treatment group. The syndecan-1 lining was disrupted after endotoxin
      treatment, and this derangement was attenuated by treatment with antithrombin.
      CONCLUSION: Antithrombin effectively maintained microcirculation and vascular
      integrity by protecting the glycocalyx in a rat sepsis model.

PMID- 30216822
TI  - A ROTEM method using APTT reagent and tissue factor as the clotting activators
      may better define bleeding heterogeneity in moderate or severe haemophilia A
      (part I: Study in plasma samples).
AB  - Bleeding heterogeneity observed in haemophilia A (HA) may attribute to that the
      available monitoring methods cannot appropriately reflect the coagulation
      profile. The present study aimed to develop a global approach by changing the
      clotting initiation way in rotational thromboelastometry (ROTEM) assay. ROTEM was
      run in Factor VIII (FVIII)-immune-depleted plasma to which different
      concentrations of recombinant VIII (rFVIII) had been added, and also in 31
      patients with HA. The clotting activators were APTT reagent (1.2 * 10-3 of the
      dose used in the original APTT method) and recombinant tissue factor (0.02
      pmol/L). In FVIII-immune-depleted plasma spiked with rFVIII, maximum velocity of
      coagulation reliably mirrored the rFVIII levels. This dose-response disappeared
      after the samples were pre-incubated with an antibody against TFPI, protein S,
      activated prothrombin complex concentrate or rFVIIa known to favour the extrinsic
      activation. In the HA patients with FVIII 0-0.21 IU/mL, APTT and ROTEM outcomes
      varied in significant correlations to FVIII activity; however, this correlation
      became non-significant when only samples with FVIII 0-0.05 IU/mL were included.
      Conclusions: The decreased coagulation in HA mostly result from
      deficiency/absence of FVIII; other pro-/anti-thrombotic proteins are also
      influential. The multiple effects may cause a mismatch between bleeding phenotype
      and FVIII concentrations. The ROTEM assay with the clotting activators i.e., tiny
      doses of APTT reagent and TF are more effective than the original APTT method as
      regards the assay sensitivity to influence by VIII activity and also to that by
      other pro-/anti-thrombotic proteins, showing the whole coagulation picture behind
      the phenotypic heterogeneity in HA.

PMID- 30216823
TI  - Revealing the 3-dimensional shape of atom probe tips by atomic force microscopy.
AB  - For the very first time, atomic force microscopy is used to determine
      quantitatively the 3-dimensional shape of an atom probe tip, which is key towards
      improved accuracy and understanding of artefacts in atom probe tomography. We
      have successfully measured by atomic force microscopy the apex and shank region
      of 3 different atom probe tips, of which two show (severe) deviations from a
      hemisphere due to either non-uniform laser light absorption or the presence of
      two different materials. Clearly, our method which overcomes the challenge of
      aligning two very sharp tips on top of each other, offers new pathways to study
      physical mechanisms in (laser-assisted) atom probe. It represents an important
      step towards improved reconstruction algorithms as the image formation in atom
      probe tomography is based on the intricate link between the tip shape (down to
      the atomic level), the electric field distribution and the ions' flight path
      towards the detector. Further on, present reconstruction algorithms solely
      account for a hemispherical tip shape, which does not hold true for most
      applications and results in complex artefacts. Therefore our method is an
      attractive novel approach to assess the 3D tip shape.

PMID- 30216824
TI  - Fluorescence turn-on chemodosimetric sensing of cyanide by cyanovinylterpyridine
      modified phthalonitrile and subphthalocyanine.
AB  - Terpyridine-attached phthalonitrile (Pn-TP) linked by cyanovinyl bond has been
      synthesized and employed for the preparation of subphthalocyanine (SubPc-TP)
      bearing conjugated terpyridine moieties. Both Pn-TP and SubPc-TP exhibited highly
      selective fluorescence turn-on in the presence of cyanide anions (CN-) based on
      chemodosimetric sensing mechanism. The conjugation of the Pn-TP molecule was
      interrupted by the addition of CN- at the cyanovinyl bond, showing the
      ratiometric fluorescence turn-on behavior. This sensing mechanism was further
      supported by density functional theory calculation and nuclear magnetic resonance
      titration studies. Optical and photophysical responses of SubPc-TP towards CN-
      were also investigated, in which similar fluorescence enhancement was observed
      due to the addition of CN- at the reactive boron trimer. The detection limit was
      estimated to be 94 nM, much below the World Health Organization-allowed level
      (1.9 MUM) of CN- in water.

PMID- 30216825
TI  - A selective fluorescence probe based on naphthalene for the detection of
      barium(II).
AB  - A designed naphthalene derivative (potassium 2,2'-(naphthalen-1
      ylazanediyl)diacetate, ND) was synthesized successfully which characterized by
      spectroscopic techniques (NMR, IR and HRMS-ESI-TOF). The sensitivity and
      selectivity were high toward Ba2+ in aqueous solution (100.0 mM HEPES buffer,
      100.0 mM KNO3, pH 7.4) over a wide variation of metal ions such as Li+, Na+, K+,
      Cs+, Mg2+, Ca2+, Al3+, Pb2+, Fe2+, Fe3+, Co2+, Ni2+, Cu+, Cu2+, Ag+, Zn2+, Cd2+
      and Ce3+. The limit of detection (LOD) was found to be 9.56*10-8 M. Density
      functional theory (DFT) calculations at the B3LYP level employing the 6-31G(d,p)
      and LANL2DZ basis set were performed for optimization of ND and ND-Ba2+ complex.
      The calculated results were consistent with a favorable complexation
      corresponding to the proposed coordination.

PMID- 30216827
TI  - Wastewater cleanup using Phlebia acerina fungi: An insight into mycoremediation.
AB  - The scarcity of available drinking water has led the researchers to develop novel
      and cost-effective ways of bioremediation process for wastewater treatment.
      Bioremediation is a cost-effective and environmentally sound method for the
      removal of toxic compounds. Such approach is not only a chemical-less effort but
      also an energy savior. In the present work Phlebia acerina, a white rot wood
      rotting fungi have been used to degrade the toxic wastewater pollutants. Congo
      Red (CR) and Eriochrome Black T (EBT) have been selected as model pollutants to
      test the wastewater cleaning ability of the fungus. The Lignin modifying enzyme
      (LME) and Cellulolytic enzyme assays (CMC) potential of Phlebia acerina helped in
      understanding the dye degradation mechanism. Under the optimum conditions, the
      fungi was able to degrade as high as 92.4% CR while the EBT was degraded to a
      maximum of 50%. Phlebia acerina was found to show first-order kinetics of dyes
      degradation. Further, the seed germination and antimicrobial assay of treated and
      untreated water were carried out in order to establish the formation of non-toxic
      end product after degradation.

PMID- 30216826
TI  - Study of handling of medico-legal cases in governmental hospitals in Cairo.
AB  - Medico-legal case (MLC) represents an integral part of medical practice in the
      emergency departments and causalities. Therefore, the physicians should have the
      sufficient knowledge of their roles and responsibilities while handling these
      cases to aid legal justice. This study on the physicians working in governmental
      hospitals in Cairo aimed to assess physicians' knowledge, practice and attitude
      regarding handling of MLCs. The study included 452 physicians working in 7
      governmental hospitals in Cairo. There were non-significant differences in
      physicians' knowledge, practice and attitude scores according to their age
      groups, gender, job titles or duration of work experience. Physicians working in
      the day surgery centre had the lowest knowledge and attitude scores. Daily rate
      of confrontation with MLCs was reported by 42% the participants (190 physicians)
      and weekly rate was reported by 21.7% (98 physicians). Writing ML report was
      found as the most frequently encountered difficulty faced the participants during
      handling of MLCs (67.1%), followed by dealing with the patients' relatives. In
      conclusion, this study revealed absence of a well defined protocol for
      recognition and handling of MLCs in all included governmental hospitals in Cairo.

PMID- 30216828
TI  - Optimization of metals extraction from spent lithium-ion batteries by sulphuric
      acid and sodium metabisulphite through a techno-economic evaluation.
AB  - The main factors that affect the extraction of metals from spent lithium-ion
      batteries by acid leaching using H2SO4, and sodium metabisulphite, were evaluated
      and optimized through a set of experiments, framed by a techno-economic approach.
      The maximum value of the profit response was obtained with the highest possible
      values of acid concentration (2.5 M) and time (2 h), a liquid/solid ratio of 5
      L/kg, and the lowest possible value of temperature (40  degrees C). After
      leaching, the electrodes active material contained in the metals decreased, while
      it was still significant in the graphite, as observed by scanning electron
      microscopy-energy dispersive spectrometry and x-ray powder diffraction. Even
      though the performed economic evaluation was a summarized outline it can be
      considered suitable to compare different leaching conditions and to determine the
      possible best combinations of factors that can optimize the profit response.

PMID- 30216829
TI  - Boosting support vector machines for cancer discrimination tasks.
AB  - Cancer is a complex disease that is caused by rapid alteration of genes.
      Prediction of the state of cancer in advance contributes to a better
      understanding of its mechanism and improves the cancer therapy process. For
      example, predicting the malignancy of tumors in advance can prevent the
      development of cancer through the early treatment and clinical management of
      tumor progression. Despite generation of extensive clinical data obtained from
      the high-throughput technologies, it is necessary to develop machine learning
      algorithms to guide the prediction process. In the study, we utilize boosting and
      develop three computational methods to increase the performance of support vector
      machines (SVM). The aforementioned methods improve the performance over existing
      state-of-the-art algorithms, including SVM and xgboost. We evaluate the proposed
      boosting approach relative to the existing algorithms by using several gene
      expression data related to oral cancer, breast cancer, pheochromocytomas and
      paragangliomas, bladder cancer, and gastric cancer. The reported results using
      several performance measures indicate that algorithms employing the proposed
      approach outperform algorithms employing the baseline approach.

PMID- 30216830
TI  - Tunable morphology of lipid/chitosan particle assemblies.
AB  - Lipid/chitosan (CS) particle assemblies have recently been developed as new
      promising carriers for drug delivery applications. The present work reports for
      the first time the formation of such assemblies by a simple spontaneous
      adsorption of lipid membranes onto the CS particle surfaces. As shown by dynamic
      light scattering (DLS) measurements, final non-aggregated assemblies with
      relatively satisfactory size distributions were obtained by using this process.
      Furthermore, a particular attention has been paid herein to the effect of the
      initial morphology of lipid membranes (i.e., vesicular or discoidal) on the
      resulting characteristics of assemblies. To this end, each one of these membranes
      was mixed with CS particles, and the obtained assemblies were observed by
      transmission electron microscopy (TEM). According to these observations, the
      vesicular lipid membranes seem to wrap mostly CS particles. In contrast, lipid
      discs are not reorganized onto the particle surface but would rather be stacked
      onto the CS particle.

PMID- 30216831
TI  - Design and microwave absorption properties of thistle-like CoNi enveloped in
      dielectric Ag decorated graphene composites.
AB  - A novel hierarchical composites for coupling thistle-like CoNi with dielectric Ag
      decorated graphene in paraffin wax as high performance microwave absorber has
      been synthesized by a facile two-step strategy. The components, particle size,
      microstructure and morphology of the resulting composites are characterized by X
      ray diffraction, X-ray photoelectron spectroscopy, Raman spectra, scanning
      electron microscope, transmission electron microscopy and energy dispersive X-ray
      spectroscopy, etc. Due to the unique flower structure and good synergistic effect
      of dielectric loss and magnetic loss, thistle-like CoNi@dielectric Ag decorated
      graphene composites have showed glorious microwave absorption intensity and
      frequency width. The maximum reflection loss of -61.9 dB can be gained at 6.96
      GHz, which has rarely been reported yet. In addition, the corresponding effective
      bandwidth with reflection loss less than -10 dB is 5.6 GHz ranging from 12.4 to
      18 GHz at only 1.67 mm thickness. This highly efficient and broad band features
      endow thistle-like CoNi@dielectric Ag decorated graphene composites with
      promising applications in microwave absorption, electromagnetic shielding,
      information safety, direct broadcast satellite and military radar fields.

PMID- 30216832
TI  - Ethylenediamine assisted functionalization of self-organized poly (d, l-lactide
      co-glycolide) patterned surface to enhance cancer cell isolation.
AB  - Protein functionalized micro-scale patterned structures are developed using a
      biocompatible polymer PLGA (poly (d, l-lactide-co-glycolide)) via thin film
      dewetting and by step-wise chemical conjugations with EDA (ethylenediamine) and
      anti-EpCAM (Epithelial Cell Adhesion Molecule) antibodies to target the
      epithelial cell adhesion molecules of cancer cells. The effectiveness of such
      protein functionalized patterned surface is checked through cell isolation
      process using blood samples spiked with different cancer cells such as MCF-7,
      A549, MDA-MB-231. An efficient capture yield of 92% is obtained with MCF-7 cells
      over a two hour incubation time. The study demonstrates the effects of cell
      concentration and incubation time on the binding of cancer cells to the modified
      patterned surfaces. For the first time, a simple and inexpensive method is
      reported to fabricate functionalized PLGA patterned surface for an efficient
      isolation of cancer cells from diluted blood samples. The method shows the
      potential to be used as an effective platform for the development of an improved
      circulating tumor cell (CTC) isolation device from the clinical blood sample.

PMID- 30216833
TI  - Nanosheets of MoSe2@M (M = Pd and Rh) function as widespread pH tolerable
      hydrogen evolution catalyst.
AB  - In this present study we have developed method for the synthesis of MoSe2
      nanosheets following a simple hydrothermal technique. Palladium (Pd) and rhodium
      (Rh) nanoparticles were decorated on the surface of MoSe2 following a simple wet
      chemical route. Pd and Rh nanoparticles decorated MoSe2 were applied for hydrogen
      evolution reaction (HER) in different pH conditions like acidic (0.5 M H2SO4),
      neutral (pH-7 buffer) and in alkaline (1 M KOH) medium and 3.5 wt% of saline
      water. Pd and Rh decorated MoSe2 show efficient activity towards HER irrespective
      of the applied electrolyte. In 0.5 M H2SO4, MoSe2 can produce 10 mA/cm2 current
      density with applied potential of -0.256 V vs. RHE. Rh decorated MoSe2 shows more
      shift in the onset potential. Upon applied potential of -0.192 V vs. RHE,
      MoSe2/Rh can produce 10 mA/cm2 current density. MoSe2/Rh is electrocatalytically
      more active than MoSe2/Pd which is established from the calculated
      electrochemically active surface area (ECSA) value. Significantly lower (47
      mV/decade) Tafel value is observed for MoSe2/Rh in 0.5 M H2SO4 which indicates
      the superior activity. MoSe2/Rh is more stable in neutral and alkaline medium
      compared to acidic medium and it can retain its own activity even after
      continuous 12 h reaction.

PMID- 30216834
TI  - Fabrication of hierarchical carbon nanosheet-based networks for physical and
      chemical adsorption of CO2.
AB  - A hierarchical carbon nanosheet-based networks (GPC) with controllable pore
      structure are developed for physical adsorption and chemical adsorption of CO2.
      The synthesis employs graphene oxide (GO) nanosheet as the structure-directing
      agent, cetyltrimethyl ammonium bromide (CTAB) as the soft template and melamine
      as the bridging molecule. The individual GO nanosheet is uniformly coated with
      the in-situ chemical polymerization of resorcinol-formaldehyde-melamine (RMF)
      polymers via electrostatic interaction with melamine. Thus, micropores with high
      specific surface area is developed from the cross-linked networks of polymers
      after carbonation and KOH activation, which is beneficial to the physical
      adsorption of CO2 at low temperature. CTAB as a soft template could induce the
      assembly of GO to form a "ring-like" stacking three-dimensional structure,
      producing macropores and mesopores with high pore volume after carbonization
      which could act as novel reservoirs to host a high loading amount of amine with
      good dispersion for CO2 chemical adsorption at elevated temperature. After
      activation with KOH, the specific surface area is up to 1555.7 m2/g, with CO2
      physical adsorption capacity of 4.62 mmol/g under 273 K and 1 bar. After loading
      PEI of 75%, the CO2 chemical adsorption capacity achieves 5.52 mmol/g under 75 
      degrees C. The outstanding advantages of hierarchical carbon nanosheet-based
      networks, including their macro-meso-microporous structures, fast diffusion
      kinetics, excellent adsorptivity and easy synthesis, endow them with good
      potential to be used in a wide range of applications.

PMID- 30216835
TI  - Depletion-interaction-driven assembly of golf ball-like particles for development
      of colloidal macromolecules.
AB  - Colloidal molecules created by clustering monodisperse particles are a
      significant model system of atoms and molecules in colloidal scale. To attain
      modelling of complex or high-molecular-weight molecules such as hyper-branched
      polymers and proteins, it is required to develop a new assembling system which
      can prepare three-dimensionally designed colloidal molecules. In this study, we
      proposed an approach for complex colloidal molecules created by association
      between golf ball-like particles and spherical particles via depletion
      interaction. Several golf ball-like particles joined together, which formed
      joined particle assemblies at the spherical particles acting as their joints in a
      depletant solution. The number of golf ball-like particles in a particle assembly
      was increased by increasing the concentration of the depletant, leading to the
      formation of branched colloidal chains of the golf ball-like particles. Because
      the golf ball-like particles in the colloidal chain flexibly rotated at their
      joints, the conformation of the chains varied in the depletant solution. The
      present results demonstrated that the golf-ball like particle that can be joined
      to form colloidal macromolecules with high association number and high
      flexibility will be a promising building block for complex colloidal model
      systems.

PMID- 30216836
TI  - Organic acid concentration thresholds for ageing of carbonate minerals:
      Implications for CO2 trapping/storage.
AB  - HYPOTHESIS: CO2 geological storage (CGS) involves different mechanisms which can
      store millions of tonnes of CO2 per year in depleted hydrocarbon reservoirs and
      deep saline aquifers. But their storage capacity is influenced by the presence of
      different carboxylic compounds in the reservoir. These molecules strongly affect
      the water wetness of the rock, which has a dramatic impact on storage capacities
      and containment security. However, precise understanding of how these carboxylic
      acids influence the rock's CO2-wettability is lacking. EXPERIMENTS: We thus
      systematically analysed these relationships as a function of pressure,
      temperature, storage depth and organic acid concentrations. A particular focus
      was on identifying organic acid concentration thresholds above which storage
      efficiency may get influenced significantly. FINDINGS: These thresholds (defined
      for structural trapping as a water contact angle theta > 90 degrees ; and for
      capillary trapping when primary drainage is unaffected, i.e. theta > 50 degrees )
      were very low for structural trapping (~10-3-10-7 M organic acid concentration
      Corganic) and extremely low for capillary trapping (10-7 M to below 10-10 M
      Corganic). Since minute organic acid concentrations are always present in deep
      saline aquifers and certainly in depleted hydrocarbon reservoirs, significantly
      lower storage capacities and containment security than previously thought can be
      predicted in carbonate reservoirs, and reservoir-scale models and evaluation
      schemes need to account for these effects to de-risk CGS projects.

PMID- 30216837
TI  - Effect of lipid chain length on nanostructured lipid carriers: Comprehensive
      structural evaluation by scattering techniques.
AB  - The objective of the present investigation was to evaluate nano-dispersed systems
      of differently chained lipids (solid phases) using various scattering techniques.
      Nanostructured lipid carriers (NLCs) were fabricated by employing the
      microemulsification methodology in which dialkyldimethyl ammonium bromide (DxDAB)
      of different alkyl chain length (x = 12, 14, 16, 18) and oleic acid were used as
      the solid lipid and liquid lipid, respectively. For the first time, the effect of
      DxDAB as a function of the chain length of the double alkyl chain on the
      structural characteristics of NLCs was investigated. Dynamic light scattering
      (DLS) and static light scattering (SLS) results showed that a small but
      systematic size increase occurs with increase in the chain length 'x' of the
      DxDAB from 12 to 16, yet D18DAB based NLCs exhibited the smallest size
      irrespective of its higher hydrophobicity. Small angle neutron scattering (SANS)
      analysis revealed the structural make up of NLCs having spherical nanoparticles
      and triaxial ellipsoidal core-shell micelles in the system. In-vitro cytotoxicity
      evaluation indicated that toxicity is simply concentration-dependent phenomena
      and NLCs with less than 5 mg/mL are preferred for better in-vivo tolerance.

PMID- 30216838
TI  - Frequency and characteristics of additionally detected ipsilateral breast lesions
      following recall at screening mammography.
AB  - PURPOSE: To determine the frequency and outcome of additionally detected
      ipsilateral breast abnormalities following recall at screening mammography.
      METHODS AND MATERIALS: We included a consecutive series of 130,338 screening
      mammograms obtained between January 1, 2014 and January 1, 2016. During 2-year
      follow-up, clinical data were collected of all recalls. Women with a bilateral
      recall (115) and women recalled for multiple lesions in one breast (165) were
      excluded from the analyses. Screening outcome parameters were determined for
      recalled women with or without evaluation of additional ipsilateral breast
      abnormalities following recall. RESULTS: A total of 3995 women were recalled
      (recall rate, 3.1%). In 258 (6.4%) of these women, another lesion was detected in
      the ipsilateral breast than the one for which she had been recalled. Biopsy was
      more frequently performed of additionally detected ipsilateral lesions than of
      recalled lesions (55.8% (144/258)) versus 39.7% (1375/3457), (p < 0.001)). The
      proportion of malignancy in recalled lesions and additionally detected lesions
      was comparable (21.5% (743/3457) versus 19.0% (49/258), p = 0.34). Of all 144
      biopsies of additionally detected ipsilateral lesions, 9 revealed a synchronous
      tumour in addition to a malignant recalled lesion, and 33 biopsies revealed
      multicentric or multifocal tumours. In 5 women, the recalled lesion turned out to
      be benign, whereas the additional lesion in a different quadrant was malignant at
      biopsy. A total of 97 biopsies showed benign findings. CONCLUSION: A substantial
      proportion of women are analyzed for additional ipsilateral breast lesions
      following recall. These lesions are more frequently biopsied than recalled
      lesions, but have a comparable probability of being malignant. The majority of
      additionally detected cancerous lesions are part of multifocal or multicentric
      malignancies.

PMID- 30216839
TI  - Probiotics SOD inhibited food allergy via downregulation of STAT6-TIM4 signaling
      on DCs.
AB  - Bacterial probiotics are of increasing use against intestinal disorders such as
      food allergy. However, the detailed molecular mechanism underlying probiotics
      mediated anti-allergic effect remains unknown. In the present study, we orally
      treated OVA-sensitized mice with Bifidobacterium infantis (BB) for two weeks. It
      was found that OVA specific-IgE and-IgG levels in serum were significantly
      decreased after BB administration. BB treatment also significantly reduced the
      release of IL-4, -5, -13 in splenocytes. Besides, after challenge with OVA, the
      occurrence of temperature drop and diarrhea was dramatically reduced in BB group.
      Moreover, the protective effect of BB on allergic mice was correlated with its
      antioxidative enzyme, superoxide dismutase (SOD). The antioxidative effect of BB
      on Dendritic cells (DCs0 was further demonstrated to be mediated by cAMP/PKA
      signaling. We also found that the mRNA and protein expression levels of TIM4 were
      attenuated in BB group. Finally, ChIP-qPCR assay studies indicate that BB reduced
      the binding of STAT6 to its response elements in the TIM4 promoter. In
      conclusion, orally administration of BB protected allergic mice via attenuation
      of oxidative stress, which further reduced TIM4 expression by inhibiting its
      transcription factor STAT6.

PMID- 30216840
TI  - Jurors' perceptions of forensic science expert witnesses: Experience,
      qualifications, testimony style and credibility.
AB  - The judicial system calls upon expert witnesses to testify in court when complex
      or specialized knowledge, beyond that of the lay person, is needed to interpret
      the evidence. Previous research has indicated that particular traits of the
      expert witness can affect their credibility in the eyes of the jury, however most
      of this research has been undertaken using mock jurors. In contrast, this study
      investigated the perceptions of real jurors. In particular, the research focused
      on the juror's perception of the forensic scientists' expertise and credibility
      during testimony in homicide cases. Data was gathered from jurors after nine
      homicide trials using both questionnaire (n=29) and direct one to one interviews
      (n=22). The jurors defined what they thought an expert witness was and what
      attributes were important in a forensic scientist. Jurors suggested that the
      expert witness's education and years of experience were more important than
      certification or laboratory accreditation. The jurors' perceptions of the
      credibility of the expert was based upon the academic qualifications of the
      expert, the confidence they portrayed in answering the questions ask of them,
      their demeanor and their status of being government employee. The use of
      narrative language and demonstrative aids by the forensic science expert witness
      to explain the evidence was explored. Jurors described a deeper understanding as
      a result of narrative testimony and this was reported to be a key factor in the
      juror's acceptance that the witness was credible.

PMID- 30216841
TI  - The validation of 'universal' PMI methods for the estimation of time since death
      in temperate Australian climates.
AB  - Forensic anthropologists have traditionally relied on their knowledge and
      experience of the decomposition stages to make an assessment of the time since
      death. However, recently new and empirical methods have been developed in various
      regions worldwide that propose to estimate the post-mortem interval (PMI) based
      on the observed decomposition changes alongside important taphonomic variables.
      Yet despite these methods being predominantly geographic specific, a number of
      methods have suggested they are effective universally and it is these 'universal'
      methods that have been inadequately test in Australia. The current study
      evaluated the accuracy of two of these methods in an Australian context,
      specifically the Greater Western Sydney region. The protocol developed by Megyesi
      et al. (2005) [1] was investigated because it is commonly cited in the literature
      and the PMI formula created by Vass (2011) [2] was also investigated because of
      its 'universal' claim. Between December 2014 and March 2016, two experimental
      trials were undertaken during the Australian summer seasons. Sixteen adult pig
      carcasses were left to decompose undisturbed on a soil surface common throughout
      the Western Sydney region and the Megyesi et al. (2005) [1] and Vass (2011) [2]
      methods were applied to the remains during this period. The results showed the
      Megyesi et al. (2005) [1] method overestimated the known PMI of remains, whereas
      the Vass (2011) [2] formula underestimated the time since death of the remains in
      these trials. The inaccuracy may be attributed to the constants which make up the
      variables in these formulas and they may not reflect the values of these
      variables in the Western Sydney region.

PMID- 30216842
TI  - Identification and characterization of an indazole-3-carboxamide class synthetic
      cannabinoid: 2-[1-(cyclohexylmethyl)-1H-indazole-3-carboxamido]-3,3
      dimethylbutanoic acid (DMBA-CHMINACA).
AB  - Illicit psychoactive substances have threatened public health worldwide. An
      active metabolite of ADB-CHMINACA and MDMB-CHMINACA was identified for the first
      time in a powder-type product found in an airmail package. The structure of
      compound 1 was elucidated by a combination of gas chromatography-mass
      spectrometry (GC-MS), liquid chromatography-high resolution mass spectrometry (LC
      HRMS), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR)
      spectroscopy. Compound 1 was proven to be an analogue of MDMB-CHMINACA, an
      indazole-based synthetic cannabinoid. The methyl ester group in MDMB-CHMINACA was
      replaced with a carboxylic acid group in compound 1. Compound 1 was determined as
      2-[1-(cyclohexylmethyl)-1H-indazole-3-carboxamido]-3,3-dimethylbutanoic acid and
      named as DMBA-CHMINACA.

PMID- 30216843
TI  - Novel validity evidence of the Psychopathy Checklist- Revised (PCL-R) in a
      representative sample of Spanish inmates.
AB  - Psychopathy Checklist-Revised (PCL-R) validation studies have been conducted
      mainly in non representative samples of North American adult male serious
      offenders. Research in other samples is needed to test the generalizability of
      PCL-R construct validity. PCL-R psychometric properties and construct validity
      were evaluated in a representative sample of 204 Spanish sentenced inmates. These
      inmates had served at least 6 months of their sentence at Pereiro de Aguiar
      prison. This sample was heterogeneous with respect to type of official charges
      and was representative, as all offenders who met the inclusion and exclusion
      criteria were invited to participate. Classical test theory indexes of
      reliability, correlations between PCL-R items, factors and facets, external
      correlations, and factor structure analysis demonstrated that PCL-R affective,
      interpersonal and lifestyle dimensions were more reliable and valid for the
      psychopathy than the antisocial construct in this Southern European sample.

PMID- 30216845
TI  - A novel thermostable beta-1,3-1,4-glucanase from Thermoascus aurantiacus and its
      application in oligosaccharide production from oat bran.
AB  - Fermentation conditions for beta-1,3-1,4-glucanase (TaGlu34) production in
      submerged culture by a thermophilic fungus, Thermoascus aurantiacus CAU830 were
      optimized. The highest enzyme activity of 3741 U/mL was obtained, and the crude
      enzyme was purified to homogeneity with a purification fold of 7.3 and a recovery
      yield of 11.6%. The molecular mass of the purified enzyme was estimated to be
      approximately 34 kDa on SDS-PAGE. TaGlu34 was most active at pH 6.0 and 75 
      degrees C, respectively. It showed excellent thermostability with thermal
      denaturing half-lives of 209, 130 and 69 min at 50, 60 and 70  degrees C,
      respectively. TaGlu34 exhibited strict substrate specificity towards barley beta
      glucan (13,527 U/mg), oat beta-glucan (12,502 U/mg) and lichenan (9225 U/mg), but
      displayed no activity on other tested polysaccharides including laminarin, xylan,
      pullulan, CMC and starch. TaGlu34 hydrolyzed barley beta-glucan and lichenan to
      yield both mainly disaccharide and trisaccharide, suggesting that it should be an
      endo type beta-1,3-1,4-glucanase. Furthermore, TaGlu34 efficiently degraded the
      beta-glucan component in oat bran to produce mainly oligosaccharides with degrees
      of polymerization (DP) 3-5, with the highest conversion ratio of 47.1%. The high
      yield and excellent enzymatic properties of TaGlu34 may make it a good candidate
      in industries.

PMID- 30216844
TI  - X-ray features to predict ankle fracture mechanism.
AB  - INTRODUCTION: The genetic Lauge-Hansen classification has been traditionally used
      for reconstruction of the mechanism of ankle injury. The ability of the Lauge
      Hansen classification to predict actual mechanism of the injury has been
      questioned in recent studies, leaving a void in medicolegal reasoning. The aim of
      this study is to identify morphologic features of malleolar fractures on plain X
      rays that may be used to reveal the fracture mechanism. MATERIAL AND METHODS:
      Radiographs of 78 patients with acute malleolar fractures were analyzed and
      compared with fracture mechanisms reported by these patients. RESULTS: A modified
      Pankovich classification of medial malleolus fractures and the presence of a
      posterior malleolus fracture were able to significantly predict the mechanism of
      fracture reported by the patient (p<0.05). Lateral fracture morphology was not
      useful for predicting the fracture mechanism except for infrasyndesmotic
      fractures pointing to a supination mechanism. CONCLUSION: A supination mechanism
      of the fracture can be predicted by observing pure ligamentous or chip-avulsion
      deltoid injury. The presence of an anterior colliculus fracture of the medial
      malleolus is correlated with a pronation mechanism. A fracture of the posterior
      malleolus correlates with pronation while an intact posterior malleolus
      correlateds with supination as a fracture mechanism. Absolute determination of
      fracture mechanism from the X-ray morphology of the fracture is impossible in the
      majority of cases.

PMID- 30216846
TI  - Extracellular vesicle-enriched microRNAs interact in the association between long
      term particulate matter and blood pressure in elderly men.
AB  - BACKGROUND: Several studies have shown that exposure to particulate matter (PM)
      may lead to increased systemic blood pressure, but the underlying biological
      mechanisms remain unknown. Emerging evidence shows that extracellular vesicle
      enriched miRNAs (evmiRNAs) are associated with PM exposure and cardiovascular
      risk. In this study, we investigated the role of evmiRNAs in the association
      between PM and blood pressure, as well as their epigenetic regulation by DNA
      methylation. METHODS: Participants (n = 22, men) were randomly selected from the
      Veterans Affairs Normative Aging Study (NAS). Long-term (1-year and 6-month
      average) PM2.5 exposure was estimated at 1 * 1-km resolution using spatio
      temporal prediction models and BC was estimated using validated time varying land
      use regression models. We analyzed 31 evmiRNAs detected in >= 90% of all
      individuals and for statistical analysis, we used mixed effects models with
      random intercept adjusted for age, body mass index, smoking, C-reactive protein,
      platelets, and white blood cells. RESULTS: We found that per each 2-standard
      deviations increase in 6-month PM2.5 ambient levels, there was an increase in
      0.19 mm Hg (95% Confidence Interval [95%CI]: 0.11, 0.28 mmHg; p < 0.001) in
      systolic blood pressure (SBP). Per each 2-standard deviations increase in 1-year
      PM2.5 levels, there was an increase in 0.11 mm Hg (95% Confidence Interval [95%
      CI]: 0.03, 0.19 mmHg; p = 0.012) in SBP in older male individuals. We also found
      that both miR-199a/b (beta = 6.13 mmHg; 95% CI: 0.87, 11.39; pinteraction = 0.07)
      and miR-223-3p (beta = 30.17 mmHg; 95% CI: 11.96, 48.39 mmHg; pinteraction =
      0.01) modified the association between 1-year PM2.5 and SBP. When exploring DNA
      methylation as a potential mechanism that could epigenetically regulate
      expression of evmiRNAs, we found that PM2.5 ambient levels were negatively
      associated with DNA methylation levels at CpG (cg23972892) near the enhancer
      region of miR-199a/b (beta = -13.11; 95% CI: -17.70, -8.52; pBonferroni< 0.01),
      but not miR-223-3p. CONCLUSIONS: Our findings suggest that expression of evmiRNAs
      may be regulated by DNA methylation in response to long-term PM2.5 ambient levels
      and modify the magnitude of association between PM2.5 and systolic blood pressure
      in older individuals.

PMID- 30216847
TI  - Surgical quality assurance in head and neck cancer trials: an EORTC Head and Neck
      Cancer Group position paper based on the EORTC 1420 'Best of' and 24954 'larynx
      preservation' study.
AB  - Quality improvement of care for patients with head and neck cancer remains a
      constant objective for the multidisciplinary team of physicians managing these
      patients. The purpose of quality assurance (QA) for head and neck surgical
      oncology and surgical trials however differs. While QA for the general head and
      neck patient aims to improve global outcome through structural changes of health
      care systems, QA for surgical trials pursues the goal to help providing
      meaningful results from a clinical trial through the definition of structure,
      process and outcome measures within the trial. Establishing a QA program for
      surgical trials is challenging largely due to the variation in the execution of
      surgical techniques. Within this article, we describe the surgical QA program,
      which was developed for the phase III European Organisation for Research and
      Treatment of Cancer (EORTC) 1420 study, a trial assessing swallowing function
      after transoral surgery compared with radiation therapy. We propose based on our
      experience to further develop surgical QA for surgical clinical trials by
      introducing two separate components, one adaptable and one non-adaptable. The
      adaptable is tailored to the scientific question and specific procedure; the non
      adaptable consists of minimal structural requirements of the clinical unit to
      participate in surgical trials at EORTC as well as guidelines and incentives for
      protocol adherence based on our experience in EORTC 24954. Finally, we strongly
      believe that surgical QA designed for clinical trials may serve as a basis for
      the development of QA surgical guidelines in clinical practice.

PMID- 30216848
TI  - Structural alterations based on naproxen scaffold: Synthesis, evaluation of
      antitumor activity and COX-2 inhibition, and molecular docking.
AB  - A new series of non-carboxylic naproxen analogues, bearing a variety of ring
      systems, such as oxadiazoles 3a-c and 6a-c, cycloalkanes 4a-d, cyclic imides 5a
      c, and triazoles 7-9 and 10a-c, was synthesized. In addition, in vitro antitumor
      activity and cyclooxygenase isozymes (COX-1/COX-2) inhibition assay of the target
      compounds 3-10 was studied. The results of the antitumor activity assays
      indicated that compounds 4b, 6c, 10b, and 10c exhibited the greatest antitumor
      activities against the tested cell lines MCF-7, MDA-231, HeLa, and HCT-116, with
      an IC50 range of 4.83-14.49 MUM. By comparison, the reference drugs doxorubicin,
      afatinib, and celecoxib yielded IC50 values of 3.18-26.79, 6.20-11.40, and 22.79
      42.74 MUM, respectively. Furthermore, in vitro COX-1/COX-2 inhibition testing
      showed that the compounds 4b, 6c, 10b, and 10c exhibited effective COX-2
      inhibition, with IC50 values of 0.40-1.20 MUM, and selectivity index (SI) values
      of >62.50-20.83, using celecoxib as a reference drug (IC50 = 0.11 MUM; COX-2 SI:
      >227.20). Compounds 6c and 10c, which were potent COX-2 inhibitors, were docked
      into the COX-2 binding site, where these compounds exhibited strong interactions.

PMID- 30216849
TI  - Recent advances of RAF (rapidly accelerated fibrosarcoma) inhibitors as anti
      cancer agents.
AB  - Frequent oncogenic mutations have been identified in MAPK (mitogen-activated
      protein kinase) signaling pathway components. As a result, MAPK pathway is
      associated with human cancer initiation, in particular RAF (rapidly accelerated
      fibrosarcoma) component. The mutation in RAF component leads to auto-activation
      of MAPK signaling pathway, stimulating the uncontrolled cell growth and
      proliferation. In last few years, diverse chemical scaffolds have been identified
      as RAF inhibitors. Most of these scaffolds show potent anti-cancer activity. The
      present review highlights the recent investigations of RAF inhibitors during the
      last five years.

PMID- 30216850
TI  - Substitution at the indole 3 position yields highly potent indolecombretastatins
      against human tumor cells.
AB  - Resistance to combretastatin A-4 is mediated by metabolic modification of the
      phenolic hydroxyl and ether groups of the 3-hydroxy-4-methoxyphenyl (B ring).
      Replacement of the B ring of combretastatin A-4 by a N-methyl-5-indolyl reduces
      tubulin polymerization inhibition (TPI) and cytotoxicity against human cancer
      cell lines but cyano, methoxycarbonyl, formyl, and hydroxyiminomethyl
      substitutions at the indole 3-position restores potent TPI and cytotoxicity
      against sensitive human cancer cell lines. These highly potent substituted
      derivatives displayed low nanomolar cytotoxicity against several human cancer
      cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal
      microscopy, and tubulin polymerization inhibitory activity studies, and promoted
      cell killing mediated by caspase-3 activation. Binding at the colchicine site was
      suggested by molecular modeling studies. Substituted combretastatins displayed
      higher potencies than the isomeric isocombretastatins and the highest potencies
      were achieved for the hydroxyiminomethyl (21) and cyano (23) groups, with TPI
      values in the submicromolar range and cytotoxicities in the nanomolar and
      subnanomolar range. Dose-response and time-course studies showed that drug
      concentrations as low as 1 nM (23) or 10 nM (21) led to a complete G2/M cell
      cycle arrest after 15 h treatment followed by a high apoptosis-like cell response
      after 48-72 h treatment. The P-glycoprotein antagonist verapamil increased 21 and
      23 cytotoxicity to IC50 values of 10-10 M, and highly potentiated the cytotoxic
      activity in 100-fold of the CHO derivative (17), in A-549 human non-small cell
      lung cancer cells. The cyano substituted indolecombretastatin 23 is by itself
      highly potent against rather resistant HT-29 and A-549 cell lines. A 3,4,5
      trimethoxyphenyl ring always afforded more potent derivatives than a 2,3,4
      trimethoxyphenyl ring.

PMID- 30216851
TI  - Novel bisphosphonates with antiresorptive effect in bone mineralization and
      osteoclastogenesis.
AB  - Bisphosphonates such as zoledronic, alendronic and risedronic acids are a class
      of drugs clinically used to prevent bone density loss and osteoporosis. Novel P-C
      P bisphosphonates were synthesized for targeting human farnesyl pyrophosphate
      synthase (hFPPS) and human geranylgeranyl pyrophosphate synthase (hGGPPS), key
      enzymes of the mevalonate pathway, and capable of anti-proliferative action on a
      number of cell lines (PC3, MG63, MC3T3, RAW 264.7, J774A.1, bone marrow cells and
      their co-colture with PC3) involved in bone homeostasis, bone formation and
      death. Among sixteen compounds, [1-hydroxy-2-(pyrimidin-2-ylamino)ethane-1,1
      diyl]bis(phosphonic acid) (10) was effective in reducing PC3 and RAW 264.7 cell
      number in crystal-violet and cell-dehydrogenase activity assays at 100 MUM
      concentration. 10 reduced differentiated osteoclasts number similarly with
      zoledronic acid in osteoclastogenesis assay. At nanomolar concentrations, 10 was
      more effective than zoledronic acid in inducing mineralization in MC3T3 and
      murine bone marrow cells. Further, 10 significantly inhibited the activity of
      hFPPS showing an IC50 of 0.31 MUM and a remarkable hydroxyapatite binding of 90%.
      Docking calculations were performed identifying putative interactions between
      some representative novel bisphosphonates and both hFPPS and hGGPPS. Then, 10 was
      found to behave similarly or even better than zoledronic acid as a anti
      resorptive agent.

PMID- 30216852
TI  - Synthesis and antiproliferative activity of 6,7-disubstituted-4-phenoxyquinoline
      derivatives bearing the 1,8-naphthyridin-2-one moiety.
AB  - A series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 1,8
      naphthyridin-2-one moiety were designed, synthesized and evaluated for their
      biological activities. The target compounds exhibited moderate to high
      antiproliferative activity against three cancer cell lines (A549, HepG2 and MCF
      7) and several compounds (25, 27, 33, 37, 41, 43, 49 and 53) were evaluated for
      the activity against c-Met kinase. The most promising compound 33 (IC50 c-Met =
      2.36 nM) showed excellent activity against A549, HepG2 and MCF-7 cell lines with
      IC50 values of 0.23 MUM, 0.42 MUM and 0.21 MUM, respectively, which was 1.5-2.1
      times of the positive control. Furthermore, compound 33 was evaluated for the
      activity against Flt3, PDGFR-alpha, PDGFR-beta, c-Kit, Flt4, ALK and EGFR kinase.
      Structure activity relationship studies indicated that mono-EWGs (such as R2 = F)
      at 4-position of moiety C was a key factor in improving the antitumor activity.
      In addition, further research on compound 33 was mainly including concentration
      dependence, apoptosis (acridine orange staining), apoptosis result analyzing and
      molecular docking.

PMID- 30216855
TI  - The prevalence and risk factors of menstrual pain of married women in Anhui
      Province, China.
AB  - PURPOSE: To investigate the prevalence and the associated risk factors for
      menstrual pain in a sample of rural married women of reproductive age in Anhui
      Province of China. METHODS: A cross-sectional study was conducted among married
      women (n = 14,828) aged 18-45 years. Data were collected through self-reported
      questionnaires. Mann Whitney U, Kruskal-Walls H tests and ordinal logistic
      regression models were used to analyze the data. RESULTS: The prevalence of no,
      moderate, severe menstrual pain was 80.1%, 18.7%, 1.2%, respectively. Lower
      educational level, lower stress level and earlier age at menarche were protective
      factors for menstrual pain while women with longer duration of menstrual flow
      tended to have menstrual pain. Compared to women with a normal body mass index
      (BMI), significantly higher odds of reporting menstrual pain were detected for
      women who were lower BMI or higher BMI. Age, length of menstrual cycle, blood
      type, anemia and previous pregnancy were not significantly associated with
      dysmenorrhea after controlling for potential confounding factors. CONCLUSIONS:
      There is high prevalence of dysmenorrhea among women in China. Our results
      suggest that reduction of stress and maintaining a normal BMI may be important
      for women to have pain-free periods.

PMID- 30216854
TI  - Transient acceleration of autophagic degradation by pharmacological Nrf2
      activation is important for retinal pigment epithelium cell survival.
AB  - Non-exudative age-related macular degeneration (AMD) is mainly caused by the
      accumulation of lipofuscin and drusen on the retinal pigment epithelium (RPE).
      Both oxidative stress and autophagic dysfunction accelerate the deposition of
      lipofuscin at the RPE. One of the key regulators in the response against
      oxidative stress is the NF-E2-Related Factor 2 (Nrf2)-kelch like ECH associated
      protein 1 (Keap1) axis, which is also closely associated with the autophagy
      pathway. Nrf2 activation upregulates the expression levels of certain anti
      oxidative enzymes [e.g. Heme oxygenase-1 (HO-1)], which attenuates oxidative
      damage. However, until now, the relationship between cytoprotective effects of
      Nrf2 activation and autophagic degradation remain unclear. To address these
      questions, we investigated the effects of a novel Nrf2 activator, RS9, on RPE
      damage. We found that RS9 protected ARPE-19 cells against NaIO3-induced oxidative
      damage, and that the protective effects of RS9 were inhibited by co-treatment
      with zinc protoporphyrin, an HO-1 inhibitor. Next, we examined the involvement of
      autophagic degradation in the protective effects of RS9. Co-treatment with RS9
      and chloroquine, a lysosomal acidification inhibitor, inhibited the protective
      effect. Furthermore, western blotting and immunostaining showed that RS9
      accelerated autophagy flux and induced transient upregulation of p62 [also known
      as sequestosome 1 (SQSTM1)]. Co-treatment with chloroquine and RS9 also inhibited
      the degradation of autophagosomes. Transient upregulation of SQSTM1 by RS9 was
      unaltered by HO-1 knockdown using siRNA. RS9 and chloroquine had the same actions
      in light damaged adult zebrafish retina as those in vitro. In conclusion, we
      clarified the relationship between acceleration of the autophagy pathway and the
      cytoprotective effects of Nrf2 activation in RPE cells and zebrafish retina.
      These findings indicated that Nrf2 activation could be a promising therapeutic
      approach for non-exudative AMD by supporting RPE maintenance.

PMID- 30216853
TI  - Sirtuin 3-dependent mitochondrial redox homeostasis protects against AGEs-induced
      intervertebral disc degeneration.
AB  - Intervertebral disc (IVD) degeneration contributes largely to pathoanatomical and
      degenerative changes of spinal structure that increase the risk of low back pain.
      Apoptosis in nucleus pulposus (NP) can aggravate IVD degeneration, and increasing
      studies have shown that interventions targeting NP cell apoptosis can ameliorate
      IVD degeneration, exhibiting their potential for use as therapeutic strategies.
      Recent data have shown that advanced glycation end products (AGEs) accumulate in
      NP tissues in parallel with the progression of IVD degeneration and form a
      microenvironment of oxidative stress. This study examined whether AGEs
      accumulation aggravates NP cell apoptosis and IVD degeneration, and explored the
      mechanisms underlying these effects. We observed that the viability and
      proliferation of human NP cells were significantly suppressed by AGEs treatment,
      mainly due to apoptosis. Furthermore, activation of the mitochondrial apoptosis
      pathway was detected after AGEs treatment. In addition, the molecular data showed
      that AGEs could significantly aggravate the generation of mitochondrial reactive
      oxygen species and prolonged activation of the mitochondrial permeability
      transition pore, as well as the increased level of Bax protein and decreased
      level of Bcl-2 protein in mitochondria. These effects could be reduced by
      antioxidant (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)
      triphenylphosphonium chloride (MitoTEMPO) and Visomitin (SKQ1). Importantly, we
      identified that impairment of Sirtuin3 (SIRT3) function and the mitochondrial
      antioxidant network were vital mechanisms in AGEs-induced oxidative stress and
      secondary human NP cell apoptosis. Finally, based on findings that nicotinamide
      mononucleotide (NMN) could restore SIRT3 function and rescue human NP cell
      apoptosis through adenosine monophosphate-activated protein kinase and peroxisome
      proliferator-activated receptor-gamma coactivator 1alpha (AMPK-PGC-1alpha)
      pathway in vitro, we confirmed its protective effect on AGEs-induced IVD
      degeneration in vivo. In conclusion, our data demonstrate that SIRT3 protects
      against AGEs-induced human NP cell apoptosis and IVD degeneration. Targeting
      SIRT3 to improve mitochondrial redox homeostasis may represent a potential
      therapeutic strategy for attenuating AGEs-associated IVD degeneration.

PMID- 30216856
TI  - Lateralizing and localizing value of seizure semiology: Comparison with scalp
      EEG, MRI and PET in patients successfully treated with resective epilepsy
      surgery.
AB  - PURPOSE: To evaluate the lateralizing and localizing value of seizure semiology
      in patients who became completely seizure free after resective epilepsy surgery.
      METHODS: We analyzed seizures of patients who were seizure free after focal
      resection limited to the temporal lobe (30 patients), frontal lobe (27 patients),
      parietal lobe (8 patients) and occipital lobe (8 patients). Three investigators
      independently analyzed video segments of seizures blinded to clinical information
      and attempted to lateralize and localize the seizure focus, based on pre-defined
      criteria. Inter-observer agreement measured and positive predictive value were
      calculated and compared with scalp interictal, ictal EEG, MRI and PET. RESULTS:
      Seizure semiology correctly lateralized 19/30 (63%) temporal lobe epilepsy
      patients (kappa = 0.64); lobar localization was correct in 27/30 patients (90%)
      (Kappa = 0.6). Twenty of 27 (74%) frontal lobe patients were correctly
      lateralized (kappa = 0.55) and localized (Kappa = 0.41). Seven of 8 (87%) of
      parietal lobe patients were correctly lateralized (kappa = 0.83) and lobar
      localization was correct in 3/8 patients (37%) (Kappa = 0.5). Seven of 8 (87%)
      occipital lobe patients were correctly lateralized (kappa = 0.67) and lobar
      localization was correct in 7/8 patients (87%) (Kappa = 0.67). Collectively,
      seizure semiology was correctly lateralizing in 74% and correctly localizing in
      77% of patients. Lateralization in secondarily generalized seizures was
      significantly higher compared to seizures that did not generalize (p = 0.0001).
      In non-lesional patients, lateralization was correct in 81% while localization
      was correct in 88% of patients. CONCLUSION: Seizure semiology has high
      lateralizing and localizing value, on par with interictal/ictal scalp EEG and
      MRI.

PMID- 30216857
TI  - Catastrophic cerebral hemorrhage and edema in a patient with pneumococcal
      meningitis.

PMID- 30216858
TI  - A review of computer aided detection in mammography.
AB  - Breast screening with mammography is widely recognized as the most effective
      method of detecting early breast cancer and has consistently demonstrated a 20
      40% decrease in mortality among screened women. Despite this, the sensitivity of
      mammography ranges between 70 and 90%. Computer aided detection (CAD) is an
      artificial intelligence (AI) technique that utilizes pattern recognition to
      highlight suspicious features on imaging and marks them for the radiologist to
      review and interpret. It aims to decrease oversights made by interpreting
      radiologists. Here we review the efficacy of CAD and potential future directions.

PMID- 30216859
TI  - A star-shaped POSS-containing polymer for cleaner leather processing.
AB  - A water-based silsesquioxane (POSS)-containing polymer, POSS-PAA, was synthesized
      by using octavinyl-POSS (V-POSS) and acrylic acid (AA) via interfacial
      polymerization. The TEM of POSS-PAA showed that the polymer formed a core-shell
      structure in aqueous solution and was well-dispersed. The star-shaped POSS-PAA
      and linear PAA were both tanned with 3.5% chromium tanning agent, and leather
      hide was tanned with 3.5% chromium tanning agent as a control. The results showed
      that the shrinkage temperature of wet-blue leather treated by POSS-PAA was
      increased by 3.5  degrees C than that of the control. The thickening rate of the
      POSS-PAA treated wet-blue leather samples was increased by 21% and 96% than the
      linear PAA-treated leather and the control leather, respectively. The EDS results
      suggested that the POSS-PAA pre-treated leather had a higher chromium content
      than the others, and the chromium distribution from the leather flesh side to the
      grain side was uniform. Moreover, the Cr2O3 content in both the POSS-PAA and the
      PAA pre-treated tanning waste water was reduced by about 50%, compared to the
      control waste. The COD and BOD of the POSS-PAA pre-tanning waste were decreased
      compared to the others. Therefore, POSS-PAA appeared to be promising for
      promoting the development of cleaner leather production.

PMID- 30216860
TI  - Relationship between extraversion personality and gray matter volume and
      functional connectivity density in healthy young adults: an fMRI study.
AB  - Extraversion and neuroticism are two main dimensions of Eysenck's personality. We
      assessed the relationship between extraversion and neuroticism with brain
      structure and function by voxel-based morphometry (VBM) and functional
      connectivity density (FCD). The resting state functional magnetic resonance image
      and high resolution structural T1 weighted images of 100 young healthy subjects
      were used in analysis. Our results showed that extraversion was negatively
      correlated with gray matter volume (GMV) of the bilateral putamen, and it was
      negatively correlated with FCD in the precuneus. No associations between
      neuroticism and brain structure and function changes. Overall, our results
      suggested that several brain regions involved in shaping of extraversion traits
      among young individuals, which may provide a neurobiological basis of
      extraversion.

PMID- 30216861
TI  - Aggressiveness of martial artists correlates with reduced temporal pole grey
      matter concentration.
AB  - Perception and practice of violence have hedonistic aspects associated with
      positive arousal (appetitive aggression). Earlier studies have mainly
      investigated the aetiology of aggressive behaviour in forensic/psychiatric
      patients. The present study examined structural brain characteristics in healthy
      people practicing violent sports (martial artists) compared to controls not
      showing violent behaviour. Aggressiveness was assessed in 21 male healthy martial
      artists and 26 age-matched male healthy controls using the aggressivity factors
      questionnaire (FAF). Participants underwent structural T1-weighted MRI. Grey
      matter (GM) differences were analysed using voxel-based morphometry. Whole-brain
      analyses of the main effects of group and aggressiveness and their interaction
      were computed. An interaction effect between group and aggressiveness was evident
      in a brain cluster comprising the left temporal pole and left inferior temporal
      gyrus. In martial artists, aggressiveness was inversely related to mean GM
      concentration in this cluster while in controls the opposite pattern was evident.
      Since these temporal brain regions are relevant for emotion/aggression regulation
      and threat appraisal, the increased GM concentration in aggressive controls might
      reflect a stronger cognitive top-down inhibition of their aggressiveness. Lower
      GM concentration in more aggressive martial artists may indicate a reduced need
      of inhibitory cognitive control because of their improved self-regulation skills.

PMID- 30216862
TI  - Serum anticholinergicity is associated with reduced prefrontal brain function in
      early course schizophrenia.
AB  - Increased anticholinergic activity resulting from pharmacotherapies used to treat
      schizophrenia is associated with poorer cognition. However the neural mechanisms
      underlying this effect are unknown. In this study of 39 early course
      schizophrenia outpatients, we demonstrate that increased serum anticholinergic
      activity is associated with reduced activation across the prefrontal cortex,
      including the dorsolateral, anterior, and medial prefrontal cortices, during two
      tasks of cognitive control. Lower activation in the dorsolateral and anterior
      prefrontal cortices mediated the association between increased anticholinergicity
      and poorer neurocognitive function. Such findings provide preliminary insight
      into how anticholinergic medications may impact cognition through reduced
      prefrontal cortical function in schizophrenia.

PMID- 30216864
TI  - Are all data useful? Inferring causality to predict flows across sewer and
      drainage systems using directed information and boosted regression trees.
AB  - As more sensor data become available across urban water systems, it is often
      unclear which of these new measurements are actually useful and how they can be
      efficiently ingested to improve predictions. We present a data-driven approach
      for modeling and predicting flows across combined sewer and drainage systems,
      which fuses sensor measurements with output of a large numerical simulation
      model. Rather than adjusting the structure and parameters of the numerical model,
      as is commonly done when new data become available, our approach instead learns
      causal relationships between the numerically-modeled outputs, distributed
      rainfall measurements, and measured flows. By treating an existing numerical
      model - even one that may be outdated - as just another data stream, we
      illustrate how to automatically select and combine features that best explain
      flows for any given location. This allows for new sensor measurements to be
      rapidly fused with existing knowledge of the system without requiring
      recalibration of the underlying physics. Our approach, based on Directed
      Information (DI) and Boosted Regression Trees (BRT), is evaluated by fusing
      measurements across nearly 30 rain gages, 15 flow locations, and the outputs of a
      numerical sewer model in the city of Detroit, Michigan: one of the largest
      combined sewer systems in the world. The results illustrate that the Boosted
      Regression Trees provide skillful predictions of flow, especially when compared
      to an existing numerical model. The innovation of this paper is the use of the
      Directed Information step, which selects only those inputs that are causal with
      measurements at locations of interest. Better predictions are achieved when the
      Directed Information step is used because it reduces overfitting during the
      training phase of the predictive algorithm. In the age of "big water data", this
      finding highlights the importance of screening all available data sources before
      using them as inputs to data-driven models, since more may not always be better.
      We discuss the generalizability of the case study and the requirements of
      transferring the approach to other systems.

PMID- 30216863
TI  - Increases in orbitofrontal cortex thickness following antidepressant treatment
      are associated with changes in resting state autonomic function in adolescents
      with major depression - Preliminary findings from a pilot study.
AB  - In adults with major depressive disorder (MDD), effective treatment has been
      associated with increases in both heart rate variability (HRV) and cortical
      thickness. However, the impact of treatment on these indices has not yet been
      examined in adolescents. Cortical thickness and HRV were measured in twelve
      adolescents with MDD before and after 8 weeks of treatment with a selective
      serotonin reuptake inhibitor (SSRI). We examined treatment-related changes in
      depression symptoms, HRV, heart rate (HR), and cortical thickness, and analyzed
      correlations among these change indices. At follow-up, patients showed
      significantly decreased depression severity, increased HRV and increased
      thickness of the left medial orbitofrontal cortex (OFC). Clinical improvement was
      associated with increased HRV and decreased HR. Increased HRV was associated with
      increased cortical thickness of left lateral OFC and superior frontal cortex. Due
      to the small sample size, results represent preliminary findings that need
      replication. Further, in the absence of a placebo arm, we cannot confirm that the
      observed effects are due solely to medication. These preliminary findings suggest
      that SSRI treatment in adolescents impacts both cortical thickness and autonomic
      functioning. Confirmation of these findings would support OFC thickness and HRV
      as neurobiological mediators of treatment outcome.

PMID- 30216865
TI  - Estimating the eco-toxicological risk of estrogens in China's rivers using a high
      resolution contaminant fate model.
AB  - The contamination of freshwater systems arises in many river basins due to
      industrialization and population growth, posing risks to ecosystems and human
      health. Despite these concerns, the fate and potential impact of many emerging
      pollutants are currently unknown, especially when the compounds are released into
      surface waters from populations distributed across large spatial scales. In order
      to address this shortcoming, a spatially-explicit contaminant fate model was
      developed as an extension of the global, vector-based river routing model
      HydroROUT. HydroROUT operates at very high spatial resolution (~500 m), simulates
      river and stream chemical transport with in-stream removal, and contains links to
      a set of lakes and reservoirs, which act as a partial sink during the transport.
      The chemical fate model was applied to China and includes a consumption and
      release module based on county-level population demographics, considers point
      source contributions from 2547 wastewater treatment plants, and accumulates
      contributions of rural and urban populations not connected to sewage treatment
      plants. As a case study, the sources and fates of the estrogens estrone (E1),
      17beta-estradiol (E2), estriol (E3), as well as the synthetic estrogenic steroid
      hormone 17alpha-ethinylestradiol (EE2) were modelled in Chinese surface water
      bodies. Preliminary validation of the results showed predictions to be within the
      ranges of concentrations reported in literature, with exception of EE2. The total
      estrogenic mass in the entire river and lake system amounted to 370 tonnes of
      estrogens, with about 1.3 tonnes per year discharged to the ocean, neighboring
      countries or to inland sinks. Under a selected baseline scenario, eco
      toxicological risk-i.e., contaminant concentrations in excess of the predicted no
      effect concentration (PNEC)-is found in 23.6% of all analyzed rivers of China
      with an average flow > 0.1 m3/s. Out of these, about 4% of rivers showed a high
      level of risk of 10 times or more above PNEC. Medium-to-large rivers are
      disproportionally affected; for example, 23.6%, 37.3%, 29.0% and 21.6% of river
      length are at risk in rivers of 1-10, 10-100, 100-1,000, and 1,000-10,000 m3/s of
      discharge, respectively, whereas no risk was predicted in the largest rivers
      (i.e., >10,000 m3/s) of China. Wastewater treatment plants process 22.5% of the
      total hormone load and thus play an important role in water quality control by
      reducing the risk in substantial portions of the river network, which would
      otherwise show elevated risk. Releases from untreated population dominate by far
      the overall contribution to risk.

PMID- 30216866
TI  - Phosphorus recovery through adsorption by layered double hydroxide nano
      composites and transfer into a struvite-like fertilizer.
AB  - Phosphorus (P) recovery from waste streams is attracting more attention due to
      the twin problems of aquatic eutrophication and global phosphorus scarcity.
      Layered double hydroxide mineral materials are promising phosphate adsorbents due
      to their excellent anion-exchange abilities and large surface area. In this
      study, the adsorption isotherms estimated the saturation capacity of calcined
      layered double hydroxide (LDH) nano-composites for phosphate as 100.7 mg-P/g
      adsorbent. Ion exchange is proposed as the major mechanism in the sorption
      process. The commonly utilized desorption method via sodium hydroxide was found
      to cause recrystallization of LDH particles in increased crystal size based on
      the dissolution-reprecipitation (D-R) mechanism. Ammonia solution was used to
      desorb P from LDH adsorbent. However, struvite crystallization occurred during
      the desorption process because struvite has a higher precipitation tendency than
      LDH with sufficient NH4+ ions. The comparison of P leaching behavior among P
      adsorbed LDH, ammonia-treated LDH, and pure struvite samples demonstrates that
      ammonia desorption probably weakened the interaction between phosphate species
      and LDH cationic layers, thus enhancing the bioavailability of P in LDH
      adsorbents. The ammonia-treated LDH has a high potential to serve like struvite
      as a P slow-releasing fertilizer.

PMID- 30216868
TI  - A proposed clinical conceptual model for the physiotherapy management of Complex
      Regional Pain Syndrome (CRPS).
AB  - There are no validated clinical models to show a reliable pathway of guaranteeing
      an effective recovery for Complex Regional Pain Syndrome (CRPS) with
      physiotherapy management. An array of medical, psychological and physiotherapy
      intervention methods show weak benefit. Spearman correlations, with significance
      p < 0.05, from an observational, prospective, longitudinal, multi-centre study of
      regional standard physiotherapy CRPS management showed complete recovery to be
      potentially associated with baseline factors of: better mental health; better
      functional ability and quality of life; higher scores of extraversion personality
      trait; lower scores of intraversion personality trait; and interventions such as
      concurrent prescription of the anticonvulsant secondary analgesia group and a
      higher intensity of physiotherapy education intervention. These correlations were
      integrated with the literature evidence and the crux of previously suggested
      models to conceptualise a clinical model that can contribute to the broader
      knowledge of physiotherapy management in CRPS that should be tested with future
      research.

PMID- 30216867
TI  - CaO2 based Fenton-like reaction at neutral pH: Accelerated reduction of ferric
      species and production of superoxide radicals.
AB  - One challenge in H2O2 based Fenton-like reaction is to break through the
      limitation of slow reduction of ferric species (FeIII). Present work describes a
      dramatic acceleration of Fenton-like reaction at neutral pH by using calcium
      peroxide (CaO2) as a source of hydrogen peroxide (H2O2) and EDTA as a chelating
      agent of ferric ions. In an optimized condition, phenol degradation in the H2O2
      system displayed an initial latent time of 60 min, while phenol can be degraded
      immediately and removed completely in 30 min in the CaO2 system. Visual MINTEQ
      analyses indicated Fe-EDTA- was the active species in the reaction. The
      contribution of 1O2 in CaO2 system was excluded by the poor selectivity in phenol
      conversion and the comparable 1O2-TEMP EPR signals in both CaO2 and H2O2 systems.
      Kinetic analyses using chloroform as the probe of O2.- suggested the high
      production rate of O2.-, which is four orders of magnitude higher than that in
      H2O2 system. The mechanism of the accelerated CaO2 based Fenton-like reactions
      was featured by that two electrons coming from CaO2 can be utilized to promote
      reduction of FeIII: an inner sphere electron transfer takes place to reduce FeIII
      EDTA and produce O2.-, and subsequently O2.- provides an electron to reduce
      another FeIII-EDTA. The revealed intrinsic reducibility in CaO2 based Fenton-like
      reaction represents a new strategy to break through the well-known rate limiting
      step of FeIII reduction in Fenton-like reaction and facilitate the removal of
      organic pollutants at neutral pHs, and also indicates a promising source of O2.-
      for diverse applications.

PMID- 30216869
TI  - Exponential consensus of discrete-time non-linear multi-agent systems via
      relative state-dependent impulsive protocols.
AB  - In this paper, we discuss the exponential consensus problem of discrete-time
      multi-agent systems with non-linear dynamics via relative state-dependent
      impulsive protocols. Impulsive protocols of which the impulsive instants are
      dependent on the weighted relative states of any two agents are introduced for
      general discrete-time multi-agent systems. The analysis of such impulsive
      protocols is transformed into an investigation on reduced fixed-time impulsive
      protocols by constructing a map, which is achieved mainly by a derived B
      equivalence method in discrete-time domain. Our main results indicate that the
      exponential consensus of the multi-agent systems via relative state-dependent
      impulsive protocols can be achieved if the reduced systems via fixed-time
      impulsive protocols can achieve exponential consensus, which need to satisfy
      suitable sufficient conditions. Numerical simulations are presented to support
      the theoretical results.

PMID- 30216870
TI  - Low-rank and sparse embedding for dimensionality reduction.
AB  - In this paper, we propose a robust subspace learning (SL) framework for
      dimensionality reduction which further extends the existing SL methods to a low
      rank and sparse embedding (LRSE) framework from three aspects: overall optimum,
      robustness and generalization. Owing to the uses of low-rank and sparse
      constraints, both the global subspaces and local geometric structures of data are
      captured by the reconstruction coefficient matrix and at the same time the low
      dimensional embedding of data are enforced to respect the low-rankness and
      sparsity. In this way, the reconstruction coefficient matrix learning and SL are
      jointly performed, which can guarantee an overall optimum. Moreover, we adopt a
      sparse matrix to model the noise which makes LRSE robust to the different types
      of noise. The combination of global subspaces and local geometric structures
      brings better generalization for LRSE than related methods, i.e., LRSE performs
      better than conventional SL methods in unsupervised and supervised scenarios,
      particularly in unsupervised scenario the improvement of classification accuracy
      is considerable. Seven specific SL methods including unsupervised and supervised
      methods can be derived from the proposed framework and the experiments on
      different data sets (including corrupted data) demonstrate the superiority of
      these methods over the existing, well-established SL methods. Further, we exploit
      experiments to provide some new insights for SL.

PMID- 30216871
TI  - Sign backpropagation: An on-chip learning algorithm for analog RRAM neuromorphic
      computing systems.
AB  - Currently, powerful deep learning models usually require significant resources in
      the form of processors and memory, which leads to very high energy consumption.
      The emerging resistive random access memory (RRAM) has shown great potential for
      constructing a scalable and energy-efficient neural network. However, it is hard
      to port a high-precision neural network from conventional digital CMOS hardware
      systems to analog RRAM systems owing to the variability of RRAM devices. A
      suitable on-chip learning algorithm should be developed to retrain or improve the
      performance of the neural network. In addition, determining how to integrate the
      periphery digital computations and analog RRAM crossbar is still a challenge.
      Here, we propose an on-chip learning algorithm, named sign backpropagation (SBP),
      for RRAM-based multilayer perceptron (MLP) with binary interfaces (0, 1) in
      forward process and 2-bit (+/-1, 0) in backward process. The simulation results
      show that the proposed method and architecture can achieve a comparable
      classification accuracy with MLP on MNIST dataset, meanwhile it can save area and
      energy cost by the calculation and storing of the intermediate results and take
      advantages of the RRAM crossbar potential in neuromorphic computing.

PMID- 30216872
TI  - Monostable multivibrators as novel artificial neurons.
AB  - Retriggerable and non-retriggerable monostable multivibrators are simple timers
      with a single characteristic, their period. Motivated by the fact that monostable
      multivibrators are implementable in large quantities as counters in digital
      programmable hardware, we set out to investigate their applicability as building
      blocks of artificial neural networks. We derive the nonlinear input-output firing
      rate relations for single multivibrator neurons as well as the equilibrium firing
      rate of large recurrent networks. We show that in rate-encoded monostable
      multivibrators networks the synaptic weights are tunable as the period ratio of
      connected units, and thus reconfigurable at run time in a counter-based digital
      implementation. This is illustrated with the task of handwritten digit
      recognition. Furthermore, we show in a task-independent manner that networks of
      monostable multivibrators are capable of nonlinear separation, when operating
      directly on pulse streams. Our research implies that pulse-coupled neural
      networks with excitable neurons showing a delayed response can perform
      computations even when working solely with suprathreshold pulses.

PMID- 30216873
TI  - Distant supervision for relation extraction with hierarchical selective
      attention.
AB  - Distant supervised relation extraction is an important task in the field of
      natural language processing. There are two main shortcomings for most state-of
      the-art methods. One is that they take all sentences of an entity pair as input,
      which would result in a large computational cost. But in fact, few of most
      relevant sentences are enough to recognize the relation of an entity pair. To
      tackle these problems, we propose a novel hierarchical selective attention
      network for relation extraction under distant supervision. Our model first
      selects most relevant sentences by taking coarse sentence-level attention on all
      sentences of an entity pair and then employs word-level attention to construct
      sentence representations and fine sentence-level attention to aggregate these
      sentence representations. Experimental results on a widely used dataset
      demonstrate that our method performs significantly better than most of existing
      methods.

PMID- 30216874
TI  - Does the single-limb stance reflect chronic ankle instability in an athlete?
AB  - BACKGROUND: The single-limb stance with closed eyes has been widely used to
      evaluate chronic ankle instability as static balance; however, there was lack of
      consideration of whether difference in age, frequency of previous ankle sprain or
      physical ability influenced single-limb stance. RESEARCH QUESTION: We
      hypothesized that the single-limb stance might not reflect subjective ankle
      instability and function on physical activity in people who perform sports
      activities. METHODS: In total, 102 high school basketball players were recruited
      to evaluate their physical performance at the beginning of the season.
      Participants were divided into five groups based on the frequency of previous
      ankle sprain. Karlsson ankle function score (K score) was considered as a
      subjective ankle function score, that was divided into various components. Each
      component and the single-limb stance test with center of pressure (COP) analysis
      was observed between the frequency of ankle sprains with one-way ANOVA and
      compared using Spearman's rank correlation coefficient to verify the relationship
      between the K score and COP. RESULTS: For COP parameters, no difference was
      observed in the history of ankle sprains. The K score was lower in participants
      with three previous ankle sprains than in those with a different number of ankle
      sprains for instability, stiffness, running, work activities, support, and total
      K score for all parameters. There were weak negative correlations (r = -0.19~
      0.35) between K score and COP parameters among participants with no history of
      ankle sprain or only once. In contrast, there were strong positive correlations
      (r = 0.69~0.87) among history of ankle sprain at third. SIGNIFICANCE: The single
      limb stance might not accurately reflect an athlete's ankle instability and
      function on physical activity. Clinically, therapists should choose suitable
      evaluation tools depending on the athlete's activity level to check for chronic
      ankle instability.

PMID- 30216876
TI  - Brood size is reduced by half in birds feeding on flutriafol-treated seeds below
      the recommended application rate.
AB  - Despite the efforts of the European Commission to implement measures that offset
      the detrimental effects of agricultural intensification, farmland bird
      populations continue to decline. Pesticide use has been pointed out as a major
      cause of decline, with growing concern about those agro-chemicals that act as
      endocrine disruptors. We report here on the effects of flutriafol, a ubiquitous
      systemic fungicide used for cereal seed treatment, on the physiology and
      reproduction of a declining gamebird. Captive red-legged partridges (Alectoris
      rufa; n = 11-13 pairs per treatment) were fed wheat treated with 0%, 20% or 100%
      of the flutriafol application rate during 25 days in late winter. We studied
      treatment effects on the reproductive performance, carotenoid-based coloration
      and cellular immune responsiveness of adult partridges, and their relationship
      with changes in oxidative stress biomarkers and plasma biochemistry. We also
      studied the effect of parental exposure on egg antioxidant content and on the
      survival, growth and cellular immune response of offspring. Exposed partridges
      experienced physiological effects (reduced levels of cholesterol and
      triglycerides), phenotypical effects (a reduction in the carotenoid-based
      pigmentation of their eye rings), and most importantly, severe adverse effects on
      reproduction: a reduced clutch size and fertile egg ratio, and an overall
      offspring production reduced by more than 50%. No effects on body condition or
      cellular immune response of either exposed adult or their surviving offspring
      were observed. These results, together with previous data on field exposure in
      wild partridges, demonstrate that seed treatment with flutriafol represents a
      risk for granivorous birds; they also highlight a need to improve the current
      regulation system used for foreseeing and preventing negative impacts of Plant
      Protection Products on wildlife.

PMID- 30216875
TI  - Sulfate radical induced degradation of Methyl Violet azo dye with CuFe layered
      doubled hydroxide as heterogeneous photoactivator of persulfate.
AB  - Persulfate (PS)-based advanced oxidation processes have aroused considerable
      attentions due to their higher efficiency and wider adaptability to the
      degradation of bio-recalcitrant organic contaminants. In this study, Cu-Fe
      layered doubled hydroxide (CuFe-LDH) was employed to degrade Methyl Violet (MV)
      through heterogeneous photo-activation of PS under visible-light irradiation. The
      reaction kinetics, degradation mechanism, catalyst stability were investigated in
      detail. Under the conditions of CuFe-LDH (3:1) dosage 0.2 g/L, PS concentration
      0.2 g/L and without initial pH adjustment, 20 mg/L MV was almost completely
      degraded within 18 min. Electron Spin Resonance (ESR) test and radical quenching
      experiment indicated that sulfate radicals (SO4-) were the dominant reactive
      oxidants for the MV decolorization, while hydroxyl radicals (OH) were also
      involved. The CuFe-LDH/PS/Vis system was applicable at wide range of pH level (3
      9). However, extreme pH level would lead to the reduction or transformation of
      SO4-. The catalyst CuFe-LDH exhibited excellent stability and maintained
      relatively high catalytic activity to PS even after four recycles. Mechanism
      study revealed that the redox cycle of Fe3+/Fe2+ and Cu2+/Cu3+ assisted by
      visible-light irradiation accounted for the enhanced generation of radicals in
      CuFe-LDH/PS/Vis system, resulting in the improved degradation of organic
      contaminants. Overall, the CuFe-LDH/PS/Vis process could be a promising approach
      for the removal of refractory organic pollutants in wastewater.

PMID- 30216877
TI  - Competitive binding of Cd, Ni and Cu on goethite organo-mineral composites made
      with soil bacteria.
AB  - Soil is a heterogeneous porous media that is comprised of a variety of organo
      mineral aggregates. Sorption of heavy metals onto these composite solids is a key
      process that controls heavy metal mobility and fate in the natural environment.
      Pollution from a combination of heavy metals is common in soil, therefore,
      understanding the competitive binding behavior of metal ions to organo-mineral
      composites is important in order to predict metal mobility and fate. In this
      study, batch experiments were paired with spectroscopic studies to probe the
      sorption characteristics of ternary CdNiCu sorbates to a binary organo-goethite
      composite made with Bacillus cereus cells. Scanning electron microscopy shows
      that goethite nano-sized crystals are closely associated with the bacterial
      surfaces. Sorption experiments show a larger adsorptivity and affinity for Cu
      than Cd/Ni on goethite and B. cereus, and the goethite-B. cereus composite. X-ray
      photoelectron spectroscopy reveals that carboxylate and phosphate functional
      moieties present on the bacterial cell walls are primarily responsible for metal
      sorption to the goethite-B. cereus composite. Synchrotron-based X-ray
      fluorescence shows that Cu and Ni are predominately associated with the bacterial
      fraction of the goethite-B. cereus composite, whereas Cd is mainly associated
      with the goethite fraction. The findings of this research have important
      implications for predicting the mobility and fate of heavy metals in soil multi
      component systems.

PMID- 30216878
TI  - Single and combined effects of microplastics and cadmium on the cadmium
      accumulation, antioxidant defence and innate immunity of the discus fish
      (Symphysodon aequifasciatus).
AB  - Microplastics (MPs) have the potential to interact with the toxicity of other
      common environmental contaminants, such as heavy metals. Here, we investigated
      the impacts of polystyrene-MPs (32-40 MUm), cadmium (Cd) and their combination on
      early juveniles of the discus fish (Symphysodon aequifasciatus) in relation to Cd
      accumulation, antioxidant defence and innate immunity. Animals were exposed to
      three concentrations of MPs (0, 50 or 500 MUg L-1) crossed with two levels of Cd
      (0 or 50 MUg L-1) for 30 days. Our findings showed that MPs and Cd had no adverse
      effects on growth and survival. Under exposure to Cd, however, accumulation of Cd
      in the body of fish decreased with increasing MP concentrations as supported by a
      reduced metallothionein content. The activities of superoxide dismutase and
      glutathione peroxidase increased with MPs but decreased with Cd. MPs, Cd or the
      mixture increased catalase activity, despite an antagonistic interaction between
      the two stressors. Glutathione levels increased when exposed to high MP
      concentrations but decreased when co-exposed to Cd. Malondialdehyde content was
      only influenced by MPs and increased with elevated MPs. MPs or Cd alone did not
      increase protein carboxyl content but showed a synergistic effect and increased
      content. MPs or Cd alone showed no effect on lysozyme activity but had a
      synergistic effect and activated activity. Activities of both acid phosphatase
      and alkaline phosphatase were enhanced by MPs, Cd or their mixture, although
      there was an antagonistic interaction between the two stressors. In contrast,
      MPs, Cd or their mixture decreased complement 3 content, despite an antagonistic
      interaction between the two stressors. Collectively, this study suggests that
      exposure to Cd led to reduced Cd accumulation in the presence of MPs.
      Nevertheless, co-exposure could induce severe oxidative stress and stimulate
      innate immunity in the juvenile S. aequifasciatus.

PMID- 30216879
TI  - Hydrogen peroxide mediates triclosan-induced inhibition of root growth in wheat
      seedlings.
AB  - Triclosan, an extensively used antimicrobial agent, enters agroecosystems when
      sewage sludge and reclaimed water are applied to agricultural fields, and may
      trigger a series of plant physiological and biochemical responses. However, few
      studies have investigated the mechanism by which plant development is affected by
      triclosan. Here, microscopic, pharmacological and biochemical analyses, and
      histochemical dye staining were used to explore the effects of triclosan on root
      growth in wheat plants. Exposure to triclosan inhibited root elongation, and
      significantly triggered hydrogen peroxide (H2O2) production and lipid
      peroxidation in wheat roots. The inhibition of root growth by triclosan was
      reversed by dimethylthiourea, a H2O2 scavenger, indicating that alterations of
      endogenous H2O2 concentrations in root cells were likely linked to triclosan
      induced root growth inhibition. The addition of butylated hydroxyanisole, a
      lipophilic antioxidant, during triclosan treatment completely prevented the
      increase of lipid peroxidation, but did not alleviate triclosan-induced reduction
      of root growth. In triclosan-treated wheat roots, the level of indole-3-acetic
      acid decreased by 68.3%, while the contents of two indole-3-acetic acid oxidative
      metabolites, indole-3-aldehyde and indole-3-carboxylic acid, increased by 71.3%
      and 314.4%, respectively. Moreover, the oxidation of auxin induced by triclosan
      in wheat roots was prevented by dimethylthiourea. These results together
      suggested that the triclosan-enhanced production of H2O2 induced auxin oxidation,
      thus leading to the suppression of root growth. Findings of this study improve
      our mechanistic understanding on how antimicrobial agents such as triclosan
      affect plant root growth.

PMID- 30216880
TI  - Environmentally relevant concentrations of carbamazepine induce liver
      histopathological changes and a gender-specific response in hepatic proteome of
      Chinese rare minnows (Gobiocypris rarus).
AB  - To assess hepatotoxicity and to determine the underlying mechanisms of
      carbamazepine (CBZ) toxicity in fish, histopathology and the liver proteome were
      examined after Chinese rare minnow (Gobiocypris rarus) were exposed to 1, 10, and
      100 MUg/L CBZ for 28 days. Histopathological changes included disruption of
      spatial structure, pyknotic nuclei, cellular vacuolization and deformation of
      cell nuclei, in addition to marked swelling of hepatocytes in all treatment
      groups. Protein analysis revealed that there were gender-specific responses in
      rare minnow following exposure, and there were 47 proteins in females and 22
      proteins in males identified as differentially abundant following CBZ treatments.
      Pathway analysis revealed that cellular processes affected by CBZ included
      apoptosis, cell differentiation, cell proliferation, and the respiratory chain,
      indicating impaired energy homeostasis. Noteworthy was that 15 proteins
      identified as different in abundance were associated with carcinogenicity.
      Relative mRNA levels for select transcripts were consistent with the changes of
      proteins N-myc downstream regulated gene (NDRG), Tropomyosin 2-Beta (TPM2) and
      annexin A4 (ANXA4). Protein pyruvate kinase, liver and RBC (PKLR) were increased
      at 1 and 100 MUg/L CBZ without significant difference in transcript levels. These
      findings characterize molecular responses and histological changes in the liver
      that generate new insights into CBZ hepatotoxicity in Chinese rare minnow.

PMID- 30216881
TI  - Are unintentionally produced polychlorinated biphenyls the main source of
      polychlorinated biphenyl occurrence in soils?
AB  - The production of polychlorinated biphenyls (PCBs) has been banned globally for
      decades, but PCB concentrations in environmental media remain relatively high,
      especially in urban areas. Emissions estimates, studies of soil gradients between
      urban and rural areas, and quantitative identification of regional sources of
      PCBs in soils are necessary for understanding the environmental behavior of PCBs.
      In this study, regional PCB emissions were estimated at a resolution of 10 km *
      10 km, and the spatial distribution of soil PCBs from urban to rural areas was
      studied along the Bohai and Yellow Sea regions. Compared with rural areas, mean
      PCB concentrations in urban soils (20.7 ng/g) were found to be higher, and
      concentrations decreased with distance from the city. Across both latitude and
      longitude directions, high PCB emissions in urban areas matched the distribution
      of total PCB concentrations in soils. The concentrations of the pollutants PCB28,
      PCB52, PCB101, PCB118, PCB138, PCB153, and PCB180 in soils originated from 5-year
      emissions, and accounted for 97%, 95%, 84%, 81%, 58%, 57%, and 27% of the total
      emissions, respectively. Unintentionally produced PCB (UP-PCB) emissions, which
      are mainly derived from cement (42%), pig iron (37%), crude steel (18%), and
      rolled steel (3%) industries, are the major contributors to PCBs in soils.
      Further identification of the sources and fates of PCBs requires a combination of
      field, laboratory, and modeling efforts.

PMID- 30216882
TI  - Using MAIAC AOD to verify the PM2.5 spatial patterns of a land use regression
      model.
AB  - Accurate spatial information of PM2.5 is critical for air pollution control and
      epidemiological studies. Land use regression (LUR) models have been widely used
      for predicting spatial distribution of ground PM2.5. However, the predicted PM2.5
      spatial patterns of a LUR model has not been adequately examined due to limited
      ground observations. The increasing aerosol optical depth (AOD) products might be
      an approximation of spatially continuous observation across large areas. This
      study established the relationship between seasonal 1 km * 1 km MAIAC AOD and
      observed ground PM2.5 in Beijing, and then seasonal PM2.5 maps were predicted
      based on AOD. Seasonal LUR models were also developed, and both the AOD and LUR
      models were validated by hold-out monitoring sites. Finally, the spatial patterns
      of LUR models were comprehensively verified by the above AOD PM2.5 maps. The
      results showed that AOD alone could be used directly to predict the spatial
      distribution of ground PM2.5 concentration at seasonal level (R2 >= 0.53 in model
      fitting and testing), which was comparable with the capability of LUR models (R2
      >= 0.81 in model fitting and testing). PM2.5 maps derived from the two methods
      showed similar spatial trend and coordinated variations near traffic roads. Large
      discrepancies could be observed at urban-rural transition areas where land use
      characters varied quickly. Variable and buffer size selection was critical for
      LUR model as they dominated the spatial patterns of predicted PM2.5.
      Incorporating AOD into LUR model could improve model performance in spring season
      and provide more reliable results during testing.

PMID- 30216883
TI  - Effects of Cd, Cu, Zn and their combined action on microbial biomass and
      bacterial community structure.
AB  - Heavy metal pollution can decrease the soil microbial biomass and significantly
      alter microbial community structure. In this study, a long-term field experiment
      (5 years) and short-term laboratory experiment (40 d) were employed to evaluate
      the effects of heavy metals (Cd, Cu, Zn), and their combinations at different
      concentrations, on the soil microbial biomass and the bacterial community. The
      ranges of heavy metal concentration in the long-term and short-term experiments
      were similar, with concentration ranges of Cd, Cu and Zn of about 0.3-1.5, 100
      500, and 150-300 mg kg-1, respectively. Microbial biomass decreased with
      increasing soil heavy metal concentrations in both the long-term and short-term
      experiments. The interaction between soil physicochemical factors (pH, TN, TC)
      and heavy metals (Cd, Cu, Zn) played a major role in change in the bacterial
      community in long-term polluted soil. In the laboratory experiment, although each
      heavy metal had an adverse effect on the microbial biomass and community
      structure, Cu appeared to have a greater role in the changes compared to Cd and
      Zn. However, the synergistic effects of the heavy metals were greater than those
      of the single metals and the synergistic effect between Cu and Cd was greater
      than that of Cu and Zn.

PMID- 30216885
TI  - Magnetite fine particle and nanoparticle environmental contamination from
      industrial uses of coal.
AB  - Recently it has been shown that there are two types of magnetite particles in the
      human brain, some, which occur naturally and are jagged in appearance, and others
      that arise from industrial sources, such as coal fired power plants, and are
      spherical. In order to confirm the latter, the magnetic component of coal ash is
      first purified and characterized by XRD, showing that it is magnetite with an
      average particle size of 211 nm. Studies confirm the coal ash magnetic behavior,
      and that the magnetite is not bound to the other components of coal ash but exist
      as an isolatable component. SEM studies confirm that in the process of burning
      coal at very high temperatures for industrial uses, the magnetite formed is
      spherically shaped, as recent studies of brain tissues of highly exposed urban
      residents have found. As such, the use of coal for industrial applications such
      as coking in the production of steel and in power plants is indicated to be a
      major source of the spherical magnetic combustion-associated magnetite fine
      particle and nanoparticle environmental pollution. The capacity of these magnetic
      particles to penetrate and damage the blood-brain-barrier and the early
      development of Alzheimer's disease hallmarks in exposed populations calls for
      detail analysis of magnetic fine and nanoparticle distribution across the world.
      Summation: Industrial coal usage produces spherical magnetic particles and
      nanoparticles, identical to those associated with neurological disorders.

PMID- 30216884
TI  - Retrospective study of foreign body-associated pathology in stranded cetaceans,
      Canary Islands (2000-2015).
AB  - Marine pollution, overrepresented by plastic, is a growing concern worldwide.
      However, there is little knowledge on occurrence and detrimental impacts of
      marine debris in cetaceans. To partially fill in this gap of knowledge, we aimed
      to investigate the occurrence and pathologies associated with foreign bodies
      (FBs) in a large cohort of cetaceans (n = 465) stranded in the Canary Islands.
      The Canary Islands shelter the greatest cetacean biodiversity in Europe, with up
      to 30 different species, of which nine are regularly present year around. We
      found at least one ingested FB in 36 out of 465 (7.74%) studied cetaceans,
      involving 15 different species, including eight out of the nine (80%) cetacean
      species present year-round in the Canary Islands. Risso's dolphin was the species
      most affected, followed by sperm whale, beaked whale and mysticetes. Plastic FB
      were the most common item found (80.56%). FB was directly associated with death
      in 13/36 (36.11%) animals. Poor body condition and deep diving behavior were
      found to be risk factors for FB ingestion, whereas the adult age was a protective
      factor. To the authors knowledge this is the first study that use statistical
      analysis to investigate risk and protective factors for FB ingestion. This study
      also provides insights of the potential impact caused by ingested FBs on the
      animal's health and mortality. This knowledge is critical to better understand
      and assess the impact of FB in cetaceans setting the scientific basis for
      prospective impact monitoring and future conservation policies.

PMID- 30216886
TI  - Ecotoxicological effects, water quality standards and risk assessment for the
      anti-diabetic metformin.
AB  - Metformin (MET) is among the most consumed pharmaceuticals worldwide. This
      compound has been frequently detected in fresh surface water. However,
      ecotoxicological information for MET is still too limited, particularly regarding
      chronic and behavioral data. This study aimed to help filling these knowledge
      gaps, by carrying out both acute and chronic studies with four different test
      organisms from three different trophic levels. We assessed different endpoints,
      including the swimming behavior of Danio rerio larvae. We also derived both short
      term and long-term environmental quality standards (EQS) for the protection of
      freshwater pelagic biota towards MET adverse effects. A risk quotient (RQ) was
      calculated for MET in fresh surface water, considering a worst-case scenario.
      Daphnia similis was by far the most sensitive species evaluated. An EC10 of 4.4
      mg L-1 was obtained from the reproduction test with D. similis. A long-term EQS
      of 88 MUg L-1 was derived and a RQ of 0.38 was obtained. An ecological risk is
      not expected for the chronic exposure of pelagic freshwater species to MET,
      considering the endpoints and the standard bioassays usually recommended in
      standard protocols. However, endocrine disruptive effects and potential
      interactive effects of MET with other co-occurring contaminants cannot be ruled
      out. To the best of our knowledge, this study presents the first data related
      with MET effects on population endpoints of D. similis and Hydra attenuata, as
      well as on the locomotor activity of D. rerio.

PMID- 30216887
TI  - Perinatal exposure to low-dose decabromodiphenyl ethane increased the risk of
      obesity in male mice offspring.
AB  - Decabromodiphenyl Ethane (DBDPE), a kind of new brominated flame retardants
      (NBFRs) used to replace DecaBDE, has been frequently detected in the environment
      and human samples. In this study, we explored its toxic effects on male mouse
      offspring after perinatal exposure to DBDPE. During the perinatal period,
      pregnant ICR mice were exposed to DBDPE (100 MUg/kg body weight) via oral gavage.
      After weaning, male offspring were fed on a low-fat diet and a high-fat diet,
      respectively. We measured and recorded body weight, liver weight, and epididymis
      fat mass, blood biochemical markers, metabolites changes in liver, and gene
      expression involved in lipid and glucose homeostasis. The results showed that
      perinatal exposure to DBDPE increased the risk of obesity in mouse offspring and
      affected triglyceride synthesis, bile secretion, purine synthesis, mitochondrial
      function and glucose metabolism, furthermore, the use of HFD feeding may further
      exacerbate these effects. All of these results show that early-life exposure to
      low doses of DBDPE can promote the development of metabolic dysfunction, which in
      turn induces obesity.

PMID- 30216888
TI  - Role of autophagy in di-2-ethylhexyl phthalate (DEHP)-induced apoptosis in mouse
      Leydig cells.
AB  - Di-2-ethylhexyl phthalate (DEHP) has been widely used as a plasticizer in
      industry. DEHP can cause testicular atrophy, yet the exact mechanism remains
      unclear. In this study, male mice were intragastrically (i.g.) administered with
      0, 100, 200 or 400 mg DEHP/kg/day for 21 days. We found that DEHP caused
      disintegration of the germinal epithelium and decreased sperm density in the
      epididymis. Furthermore, there was a significant increase in the levels of
      cleaved Caspase-8, cleaved Caspase-3 and Bax proteins and a decrease in Bcl2
      protein. The results indicated that DEHP could induce apoptosis of the testis
      tissue. Meanwhile, DEHP significantly induced autophagy in the testis tissues
      with increases in LC3-II, Atg5 and Beclin-1 proteins. The serum testosterone
      concentration decreased in the DEHP-treated group, implying that DEHP might lead
      to Leydig cell damage. Furthermore, oxidative stress was induced by DEHP in the
      testis. To further investigate the potential mechanism, mouse TM3 Leydig cells
      were treated with 0-80 MUM DEHP for 48 h. DEHP significantly inhibited cell
      viability and induced cell apoptosis. Oxidative stress was involved in DEHP
      induced apoptosis as N-Acetyl-L-cysteine (NAC), an inhibitor of oxidative stress,
      could rescue the inhibition of cell viability and induction of apoptosis by DEHP.
      Similar to the in vivo findings, DEHP could also induce cell autophagy. However,
      inhibition of autophagy by 3-Methyladenine (3-MA) significantly increased cell
      viability and inhibited apoptosis. Taken together, oxidative stress was involved
      in DEHP-induced apoptosis and autophagy of mouse TM3 Leydig cells, and autophagy
      might play a cytotoxic role in DEHP-induced cell apoptosis.

PMID- 30216889
TI  - Co-contaminant effects on 1,4-dioxane biodegradation in packed soil column flow
      through systems.
AB  - Biodegradation of 1,4-dioxane was examined in packed quartz and soil column flow
      through systems. The inhibitory effects of co-contaminants, specifically
      trichloroethene (TCE), 1,1-dichloroethene (1,1-DCE), and copper (Cu2+) ions, were
      investigated in the columns either with or without bioaugmentation with a 1,4
      dioxane degrading bacterium Pseudonocardia dioxanivorans CB1190. Results indicate
      that CB1190 cells readily grew and colonized in the columns, leading to
      significant degradation of 1,4-dioxane under oxic conditions. Degradation of 1,4
      dioxane was also observed in the native soil (without bioaugmentation), which had
      been previously subjected to enhanced reductive dechlorination treatment for co
      contaminants TCE and 1,1-DCE. Bioaugmentation of the soil with CB1190 resulted in
      nearly complete degradation at influent concentrations of 3-10 mg L-1 1,4-dioxane
      and a residence reaction time of 40-80 h, but the presence of co-contaminants,
      1,1-DCE and Cu2+ ions (up to 10 mg L-1), partially inhibited 1,4-dioxane
      degradation in the untreated and bioaugmented soil columns. However, the
      inhibitory effects were much less severe in the column flow-through systems than
      those previously observed in planktonic cultures, which showed near complete
      inhibition at the same co-contaminant concentrations. These observations
      demonstrate a low susceptibility of soil microbes to the toxicity of 1,1-DCE and
      Cu2+ in packed soil flow-through systems, and thus have important implications
      for predicting biodegradation potential and developing sustainable, cost
      effective technologies for in situ remediation of 1,4-dioxane contaminated soils
      and groundwater.

PMID- 30216890
TI  - Radiological comparison of a FDNPP waste storage site during and after
      construction.
AB  - The clean-up effort that is occurring across the region affected by the 2011
      Fukushima Daiichi Nuclear Power Plant accident is unprecedented in its magnitude
      as well as the financial cost that will eventually result. A major component of
      this remediation is the stripping of large volumes of material from the land
      surface, depositing this into large waste storage bags before placing these 1
      cubic meter bags into specially constructed stores across Fukushima Prefecture.
      In this work, using an unmanned aerial vehicle to perform radiological surveys of
      a site, the time-resolved distribution of contamination during the construction
      of one of these waste storage sites was assessed. The results indicated that
      radioactive material was progressively leaching from the store into the
      surrounding environment. A subsequent survey of the site conducted eight months
      later revealed that in response to this survey and remedial actions, the
      contamination issue once existing on this site had been successfully resolved.
      Such results highlight the potential of low-altitude unmanned aerial systems to
      easily and rapidly assess site-wide changes over time - providing highly-visual
      results; therefore, permitting for prompt remedial actions to be undertaken as
      required. Use of UAV radiation mapping and airborne photogrammetry to produce a
      time-resolved assessment of remediation efforts within a Fukushima temporary
      storage facility.

PMID- 30216891
TI  - Adolescents in crisis: A geographic exploration of help-seeking behavior using
      data from Crisis Text Line.
AB  - Nearly 3 out of 4 all lifelong mental disorders occur by the age of twenty-four.
      Remote crisis support holds great potential in filling a critical gap in
      complementing and expanding access to mental health services for acute episodes
      of mental distress in adolescents and young adults; yet little is understood
      about the individual factors that influence help-seeking behavior in this group.
      Recent evidence suggests technology-based mental health services have high
      acceptability among youth and may be used to treat anxiety and depression. The
      objective of this study was to examine county-level help-seeking behavior among
      adolescents and young adults using Crisis Text Line (CTL). CTL is a free, text
      based crisis counseling service that has been available nationally since 2013.
      Spatial error regression was used to (1) identify the individual-level factors
      that correlate with help-seeking behavior for depression, anxiety, and suicidal
      thoughts and (2) to explore the geographic trends in text-based help-seeking
      behavior between adolescents and young adults across the rural-urban continuum.
      Increased rates of text-based help-seeking occurred in counties with higher mean
      household incomes, higher divorce rates, and lower residential stability.
      Rurality was the strongest predictor for low rates of help-seeking, and this
      finding is particularly concerning in light of elevated rates of suicide among
      rural counties. Rural communities, particularly those with low support-seeking
      behavior and comparatively high suicide rates, should be the target of future
      research and outreach.

PMID- 30216892
TI  - Generation of induced pluripotent stem cell line(ZZUi006-A)from a patient with
      myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is a dominantly inherited neurodegenerative
      disease caused by a CTG repeat expansion close to the DMPK gene. The fibroblasts
      from a patient with DM1 were successfully converted to induced pluripotent stem
      cells (iPSCs), designated ZZUi006-A, by employing episomal plasmids expressing
      OCT3/4, SOX2, KLF4, LIN28, L-MYC. The ZZUi006-A cell line may provide a robust
      platform for further study of DM1 pathogenesis as well as drug testing and gene
      therapy research.

PMID- 30216893
TI  - Assessing chronic toxicity of aluminium, gallium and molybdenum in tropical
      marine waters using a novel bioassay for larvae of the hermit crab Coenobita
      variabilis.
AB  - A novel bioassay is presented that allows for the estimation of the chronic
      toxicity of contaminants in receiving tropical marine environments. Relevant
      procedures to identify contaminants of concern and evaluate hazards associated
      with contamination in these environments have long remained inadequate. The 6-day
      bioassay is conducted using freshly hatched planktonic larvae of the hermit crab
      Coenobita variabilis and is targeted at generating environmentally relevant,
      chronic toxicity data. The developmental endpoint demonstrated consistently high
      control performance and was validated through the use of copper as a reference
      toxicant. In addition, the biological effects of aluminium, gallium and
      molybdenum were assessed. The endpoint expressed high sensitivity to copper (EC10
      = 24 ug L-1) and moderate sensitivity to aluminium (EC10 = 312 ug L-1), whereas
      gallium and molybdenum elicited no obvious effects, even at high concentrations
      (EC10 > 6000 ug L-1), providing valuable information on the toxicity of these
      elements in tropical marine waters for derivation of water quality guidelines or
      testing of compliance limits.

PMID- 30216894
TI  - Plant leaf extracts as photocatalytic activity tailoring agents for BiOCl towards
      environmental remediation.
AB  - The inducement of plant leaf extracts for the synthesis of various nanostructures
      has intrigued researchers across the earth to explore the mechanisms of
      biologically active compounds present in the plants. Herein, a green modified
      hydrolysis route has been employed for the synthesis of bismuth oxychloride i.e.
      BiOCl-N, BiOCl-T and BiOCl-A using plant extracts of Azadirachta indica (Neem),
      Ocimum sanctum (Tulsi), and Saraca indica (Ashoka), and; simultaneously, without
      plant extract (BiOCl-C), respectively. The as-prepared samples were examined by
      several microscopic and spectroscopic techniques which revealed that the
      biosynthesized BiOCl attained certain favorable features such as hierarchical
      nano-flower morphology, higher porosity, higher specific surface area and
      narrower band gap compared to BiOCl-C. The degradation of methyl orange (MO) and
      bisphenol A (BPA) using biosynthesized BiOCl were improved by 21.5% within 90 min
      and 18.2% within 600 min under visible light irradiation, respectively. The
      photocurrent response, electrochemical impedance spectroscopy (EIS) and
      photoluminescence (PL) studies indicated the effective inhibition of the electron
      hole pair recombination and enhanced photocatalytic activity of the
      biosynthesized BiOCl.

PMID- 30216895
TI  - Toxicity evaluation of leached of sugarcane vinasse: Histopathology and
      immunostaining of cellular stress protein.
AB  - Sugarcane vinasse is a residue generated at a rate fifteen times greater than the
      ethanol production. Because of its high organic and micronutrient content, this
      residue is used as a fertilizer on sugarcane crops. However, when used in large
      quantities, vinasse can saturate the soil and contaminate nearby water resources
      by percolation and leaching. Given the proven toxic potential of in natura
      vinasse, the present study aimed to evaluate the toxic potential of leached
      sugarcane vinasse using Nile tilapia (Oreochromis niloticus) as a test organism.
      A bioassay was performed after vinasse percolation in laboratory soil columns.
      The bioassay included one control group containing fresh water and two treatment
      groups, the first exposed to a 2,5% dilution of leached of vinasse and the second
      to a 2,5% dilution of in natura vinasse. After exposure, histopathological
      analysis was performed in gills and livers, and the latter were labelled for
      HSP70 proteins. No significant changes were detected in the gills of the exposed
      fish. However, in the liver, both in natura and leached vinasse induced
      statistically significant histopathological changes. These changes include
      hydropic degeneration, cell boundary losses, pyknotic nuclei and cellular
      disorganization. HSP70 expression significant increase in liver of both treatment
      groups were observed, being higher for the in natura vinasse exposed group.
      Results suggested that both leached vinasse and in natura vinasse were toxic, its
      still able to provoke histological changes and induce the cytoprotective response
      in exposed fish liver, evidenced by a immunostaining of cellular stress proteins.
      Thus, in order to reduce its environmental impact, appropriated effluent disposal
      is essential.

PMID- 30216896
TI  - Systematic analysis of occurrence and variation tendency about 58 typical
      veterinary antibiotics during animal wastewater disposal processes in Tianjin,
      China.
AB  - Residue of veterinary antibiotics (VAs) in the animal breeding industry has
      become a problematic environmental issue. However, the residual levels of VAs as
      well as their variation tendency, degradation mechanisms and relationships with
      other parameters during animal wastewater disposal processes are still obscure.
      This study measured different samples during wastewater disposal processes from
      three farms, and systematically analyzed the residue, migration and removal of 58
      kinds of typical VAs (6 classes) in Tianjin, China. The results showed that about
      44 kinds of VAs were quantitatively detected. Tetracycline antibiotics (TCs)
      usually had higher residual concentrations than other classes of VAs in the raw
      wastewater; the highest residual concentration was 130.67 +/- 5.90 MUg/L which
      occurred for chlortetracycline (CTC). Pig farms generally had more VAs species
      and higher residual concentrations than dairy farms, and the proportion of
      different VAs was similar for dairy farms. The final removal rates of different
      VAs classes varied largely (negative to > 99.87%), and the highest removal rates
      usually occurred in biological processes for adsorption and biodegradation
      effects, and occasionally occurred in the final effluents. The correlation
      coefficients between VAs removal rates and chemical oxygen demand (COD) removal
      rates were much higher than those of total nitrogen (TN), total phosphorus (TP)
      and ammonia nitrogen (NH4-N) in pig farms, while opposite conclusion was obtained
      in dairy farms. Among different classes, TCs presented the highest daily mass
      loading of ND ~ 10,453.8 +/- 471.7 mg/d in the influent and ND ~ 1141.6 +/- 58.9
      mg/d in the effluent in farm 1.

PMID- 30216897
TI  - Statistical learning and spelling: Evidence from an incidental learning
      experiment with children.
AB  - Statistical learning processes-akin to those seen in spoken language acquisition
      (Saffran et al., 1996)-may be important for the development of literacy,
      particularly spelling development. One previous study provides direct evidence
      for this process: Samara and Caravolas (2014) demonstrated that 7-year-olds
      generalize over permissible letter contexts (graphotactics) in novel word-like
      stimuli under incidental learning conditions. However, unlike in actual
      orthography, conditioning contexts in Samara and Caravolas' (2014) stimuli
      comprised perfectly correlated, redundant cues in both word-initial and word
      final positions. The current study explores whether 7-year-olds can extract such
      constraints in the absence of redundant cues. Since theories of literacy
      development predict greater sensitivity to restrictions within word-final units,
      we also contrast learning in word-initial and word-final units. We demonstrate
      that-for 7-year-old learners in two linguistic contexts (English and Turkish)
      there is substantial evidence for the learning of both types of restriction.

PMID- 30216898
TI  - Attention rapidly reorganizes to naturally occurring structure in a novel
      activity sequence.
AB  - Fluent event processing involves selectively attending to information-rich
      regions within dynamically unfolding sensory streams (e.g., Newtson, 1973). What
      counts as information-rich likely depends on numerous factors, however, including
      overall event novelty and local opportunity for repeated viewing. Using Hard,
      Recchia, and Tversky's (2011) method, we investigated the extent to which these
      two variables affected viewers' attentional patterns as events unfolded.
      Specifically, we recorded viewers' "dwell times" as they advanced through two
      slideshows depicting distinct methods of shoelace tying varying in novelty but
      equated on other dimensions. Across two experiments, novelty sparked increased
      dwelling overall, and viewers' dwelling patterns displayed rapid and systematic
      reorganization to structure within the activity stream after just one viewing of
      distinctively novel content. As well, increased dwelling positively predicted
      memory performance. These findings newly illuminate reorganization in attention
      as relevant information within novel activity sequences is quickly incorporated
      to guide event processing and support event memory.

PMID- 30216899
TI  - Revisiting the bilingual lexical deficit: The impact of age of acquisition.
AB  - Whereas the cognitive advantages brought about by bilingualism have recently been
      called into question, the so-called 'lexical deficit' in bilinguals is still
      largely taken for granted. Here, we argue that, in analogy with cognitive
      advantages, the lexical deficit does not apply across the board of bilinguals,
      but varies as a function of acquisition trajectory. To test this, we implement a
      novel methodological design, where the variables of bilingualism and first/second
      language status have been fully crossed in four different groups. While the
      results confirm effects of bilingualism on lexical proficiency and processing,
      they show more robust effects of age of acquisition. We conclude that the
      traditional view of the linguistic costs of bilingualism need to give way to a
      new understanding of lexical development in which age of acquisition is seen as a
      major determinant.

PMID- 30216901
TI  - Mucosal permeability and mast cells as targets for functional gastrointestinal
      disorders.
AB  - The intestinal mucosa is constantly exposed to harmful luminal content, and
      uptake is closely controlled and regulated by neuro-immune factors. If control is
      broken, it might lead to ongoing enhanced mucosal permeability, potentially
      resulting in functional gastrointestinal disorders. The importance of mast cells
      in the regulation of the mucosal barrier has become obvious, and increased
      numbers and more activated mast cells have been observed in irritable bowel
      syndrome, functional dyspepsia and gastroesophageal reflux disease. To target the
      disturbed mucosal permeability, directly or via mast cells, is therefore
      currently of major interest. For example, administration of mast cell stabilizers
      and probiotics have shown promising effects in patients with functional
      gastrointestinal disorders.

PMID- 30216900
TI  - Periprosthetic pathologic fracture following tibial Echinoccocosis: A case
      report.
AB  - INTRODUCTION: Hydatid disease in humans caused by the parasitic tapeworm
      Echinococcus granulosus has an osseous involvement of about 0.5%-2.5% of all
      cases in humans. The location of hydatid cysts in the tibia is seldom described
      in the medical literature, and its diagnosis and treatment is challenging. CASE
      REPORT: This paper presents a patient, with a long term, well tolerated,
      bilateral total knee arthroplasty (TKA), treated at our clinic, with a recent
      history of pain and oedema in her left upper leg. After achieving a,
      radiologically and histhopathologically, well documented, diagnosis of
      Echinoccocosis lesion in her left proximal tibia, a surgical intervention was
      planed, a wide resection of the cyst performed, and a specific anti-helmintic
      therapy was instituted. Four years later, she returns to our observation
      complaining of pain and unable to bear weight on her left knee, from which a
      pathologic fracture, adjacent to the tibial component, was diagnosed. After
      surgical debridement of the newly advanced hydatid cyst growth, the TKA was
      revised, and due to the tibial component failure and the femoral implant
      loosening, a semi-constrained total knee revision arthroplasty was executed.
      Functional outcome was excellent. CONCLUSION: Although challenges in treatment of
      musculoskeletal hydatid cysts (HC) lesions have been documented, data regarding
      the musculoskeletal HC lesions resembling tumor is scarce, and those resulting in
      a prosthetic failure have not been published. The authors intend to add data
      concerning the therapeutic approach to this entity.

PMID- 30216902
TI  - Visual and linguistic narrative comprehension in autism spectrum disorders:
      Neural evidence for modality-independent impairments.
AB  - Individuals with autism spectrum disorders (ASD) have notable language
      difficulties, including with understanding narratives. However, most narrative
      comprehension studies have used written or spoken narratives, making it unclear
      whether narrative difficulties stem from language impairments or more global
      impairments in the kinds of general cognitive processes (such as understanding
      meaning and structural sequencing) that are involved in narrative comprehension.
      Using event-related potentials (ERPs), we directly compared semantic
      comprehension of linguistic narratives (short sentences) and visual narratives
      (comic panels) in adults with ASD and typically-developing (TD) adults. Compared
      to the TD group, the ASD group showed reduced N400 effects for both linguistic
      and visual narratives, suggesting comprehension impairments for both types of
      narratives and thereby implicating a more domain-general impairment. Based on
      these results, we propose that individuals with ASD use a more bottom-up style of
      processing during narrative comprehension.

PMID- 30216903
TI  - Antimicrobial dispersions and films from positively charged styrene and acrylic
      copolymers.
AB  - Antimicrobial properties of methyl methacrylate - ethyl acrylate and styrene -
      ethyl acrylate copolymers, both as latexes and after film formation were tested.
      The polymers were synthesized using a cationic surfactant, cetytrimethylammonium
      bromide (CTAB) as an emulsifier, in presence of either a cationic or an anionic
      initiator. The resulting latex particles showed sizes between 50 and 320 nm
      (larger for the anionic initiator), and zeta-potential between +30 and +70 mV
      (more positive for the cationic initiator). Dialysis did not change significantly
      the size distribution and zeta-potential of the latexes, and most of them
      inhibited growth of Gram-negative (E. coli), Gram-positive (S. aureus, B.
      subtilis) and yeast (C. albicans). On the other hand, only few compositions were
      effective against Gram-negative P. aeruginosa. Both completely ("dry") and
      incompletely ("wet") formed films produced from the respective latexes showed
      similar, although less pronounced antimicrobial activity pattern. The analysis of
      streaming potential for the films confirmed that part of the positive surface
      charge brought by non-covalent binding of CTAB to the polymer chains, is lost
      during dialysis of the latexes and during rinsing, especially under high-shear
      flow. From the practical point of view, films with the best mechanical and
      antimicrobial properties can be achieved using polymers with high proportion of
      ethyl acrylate, while nature of the co-monomer and initiator do not play crucial
      roles.

PMID- 30216904
TI  - Surface charging by the cold plasma discharge of lentil and pepper seeds in
      comparison with polymers.
AB  - Cold plasma treatment charges organic surfaces. Surface density of the electrical
      charge supplied by cold radiofrequency plasma to the pepper and lentil seeds and
      various polymers: polyethylene, polystyrene, polycarbonate and poly(methyl
      methacrylate) was established experimentally. The surface charge density for all
      of studied interfaces, with one exception of polycarbonate was estimated as
      sigma~0.75-3.7MUC/m2; for the polycarbonate it was almost an order of magnitude
      larger, namely sigma~7-9MUC/m2. The kinetics of the surface charge leakage was
      studied. The characteristic time of temporal change in the surface density of the
      electrical charge gained by the seeds is markedly larger than that of synthetic
      polymers.

PMID- 30216905
TI  - Polyaconitic acid/functional amine/azo dye composite as a novel hyper-branched
      polymer for cotton fabric functionalization.
AB  - A new hyperbranched polymer based on aconitic acid and two different amine
      (triethnaol amine and diethylenetriamine) with different functional groups;
      hydroxyl and amine groups respectively was successfully synthesised by A2B3
      polymerization technique and characterised using Fourier Transform Infrared (FT
      IR), Nuclear Magnetic Resonance (NMR), rheological properties, antimicrobial and
      cytotoxicity activity. In addition, a new heterocyclic azo dye was synthesised
      and characterised using FT-IR, NMR, mass spectra and antimicrobial activity.
      Characterisation provides that both composites and azo dye have been well
      prepared. A mixture from both hyberbranched polymer and synthesised azo dye have
      been applied to cotton fabrics. Evaluation of treated fabrics shows that, the
      surface of treated fabrics has a thin film from applied composite which coated
      the whole fibre surface. Treated fabrics have good antimicrobial activity against
      gram positive, gram negative bacteria and fungi. Fastness properties, physical
      and mechanical properties for treated fabrics were also evaluated.

PMID- 30216906
TI  - Evidence for a differential visual M300 brain response in gamblers.
AB  - OBJECTIVE: Gambling disorder is the first behavioral addiction recognized in the
      DSM-5. This marks the growing realization that both behavioral and substance
      related addictions are manifestations of an 'addicted brain', displaying similar
      altered neurophysiological mechanisms. A decreased electrophysiological visual
      P300 is considered a hallmark effect of substance-related addictions, but has not
      yet been shown in behavioral addictions. METHODS: Magnetoencephalographic
      recordings of 15 gamblers and 17 controls were taken as they performed a cue
      reactivity paradigm in which they passively viewed addiction- and non-addiction
      related cues. RESULTS: The main finding of the study is a reduction in the
      magnetic counterpart of P300 (M300) for gamblers beyond cue condition over
      frontal regions. Additionally, we found a significant group by cue-type
      interaction. Gamblers exhibited heightened sensitivity to addiction-related cues
      in regions corresponding to the frontoparietal attentional network, whereas
      controls exhibited an opposite effect localized to the right insula. CONCLUSIONS:
      The results suggest that a reduced P300 characterizes addictions in general, not
      just substance-related addictions, thus providing important neurophysiological
      support for the inclusion of behavioral addictions in the DSM-5 and in the
      incentive-sensitization theory. SIGNIFICANCE: The study offers important insights
      into neural mechanisms underlying behavioral addictions, and may assist in
      developing better prevention and intervention strategies.

PMID- 30216907
TI  - The median to ulnar cross-sectional surface area ratio in carpal tunnel syndrome.
AB  - OBJECTIVE: To investigate the use of a sonographic median-to-ulnar cross
      sectional area ratio (MUR) in diagnosis of carpal tunnel syndrome (CTS); and to
      compare the MUR with currently used sonographic parameters, and
      electrophysiology. METHODS: Subjects with CTS and healthy volunteers underwent
      ultrasound studies of the median and ulnar nerves in the wrist and forearm.
      Various sonographic parameters and ratios were calculated, and compared between
      CTS patients and controls. The sensitivity and specificity of the different
      parameters were compared by plotting receiver operator characteristic curves.
      Correlations of sonographic results with electrophysiologic studies were
      calculated. RESULTS: The MUR was increased in patients with CTS, in comparison
      with controls. A cut-point of >2.09 yielded a sensitivity of 86% and specificity
      of 84%. This was comparable to the currently used ultrasound metrics for CTS. The
      MUR also correlated with electrophysiologic severity. CONCLUSIONS: The MUR is an
      effective means of diagnosing CTS and correlates with electrophysiologic
      severity. SIGNIFICANCE: This report provides support for the use of the MUR in
      the sonographic diagnosis of CTS.

PMID- 30216908
TI  - Neurophysiological monitoring during cervical spine surgeries: Longitudinal costs
      and outcomes.
AB  - OBJECTIVES: Well-designed longitudinal studies assessing effectiveness of
      intraoperative neurophysiologic monitoring (IONM) are lacking. We investigate
      IONM effects on cost and administrative markers for health outcomes in the year
      after cervical spine surgery. METHODS: We identified single-level cervical spine
      surgeries in commercial claims. We constructed linear regression models
      estimating the effect of IONM (controlling for patient demographics, pre
      operative health, services during index admission) on total spending,
      neurological complications, readmissions, and outpatient opiate usage in the year
      following index surgery. RESULTS: IONM was associated with increased spending
      during index admission of $1229 (p = 0.001), but decreased spending post
      discharge of $1615 (p = 0.010), for a net - $386 (p = 0.608) for the year after
      surgery. Shorter length of stay (0.116 days, p = 0.004) and fewer readmissions
      (20.5 per thousand, p = 0.036) accounted for some post-discharge savings. IONM
      was associated with decreased rates of nervous system complications (4/1000, p =
      0.048) and post-discharge opiate use (17 prescriptions/1000, p = 0.050) in the
      year after index admission. CONCLUSIONS: IONM was associated with administrative
      markers suggesting improved health outcomes after cervical spine surgery without
      greater costs for the year. SIGNIFICANCE: This study suggests IONM may have
      lasting health and cost benefits.

PMID- 30216909
TI  - The effects of aging on early stages of the auditory deviance detection system.
AB  - OBJECTIVE: The aging effects on auditory change detection have been studied using
      the Mismatch Negativity (MMN) potential. However, recent studies have found
      earlier correlates of deviance detection at the level of the middle-latency
      response (MLR) and the effects of aging on this deviant-related response have not
      yet been clarified. The purpose of this study was to examine the effects of aging
      on both levels of the auditory deviance detection system. METHODS: MMN and MLR
      responses were recorded in 33 young and 29 older adults from 32 scalp electrodes
      during frequency oddball and swapped-oddball conditions. RESULTS: In the young
      group, modulation of MLR and a clear MMN response were observed, whereas in the
      aged group, no evidence of deviance detection was found at the level of MLR and
      the MMN amplitude was significantly diminished. CONCLUSIONS: Based on the
      obtained results, aging affects both levels of the auditory deviance detection
      system which seems to be a result of deficits in regularity encoding along the
      auditory hierarchy. SIGNIFICANCE: The current findings suggest that age-related
      physiological changes result in deficits in regularity encoding, starting from
      early stages of processing. This might eventually affect stream segregation and
      induce difficulties in understanding speech in complex environments.

PMID- 30216910
TI  - Nerve ultrasound findings differentiate Charcot-Marie-Tooth disease (CMT) 1A from
      other demyelinating CMTs.
AB  - OBJECTIVE: Ulnar/median motor nerve conduction velocity (MNCV) is <=38 m/s in
      demyelinating Charcot-Marie-Tooth disease (CMT). Previous nerve high resolution
      ultrasound (HRUS) studies explored demyelinating CMT assuming it as a homogeneous
      genetic/pathological entity or focused on CMT1A. METHODS: To explore the spectrum
      of nerve HRUS findings in demyelinating CMTs, we recruited patients with CMT1A (N
      = 44), CMT1B (N = 9), CMTX (N = 8) and CMT4C (N = 4). They underwent nerve
      conduction study (NCS) and HRUS of the median, ulnar, peroneal nerve, and the
      brachial plexus. RESULTS: Median, ulnar and peroneal MNCV significantly differed
      across CMT subtypes. Cross sectional area (CSA) was markedly and diffusely
      enlarged at all sites, except entrapment ones, in CMT1A, while it was slightly
      enlarged or within normal range in the other CMTs. No significant right-to-left
      difference was found. Age had limited effect on CSA. CSAs of some CMT1A patients
      largely overlapped with those of other demyelinating CMTs. A combination of three
      median CSA measures could separate CMT1A from other demyelinating CMTs.
      CONCLUSIONS: Nerve HRUS findings are heterogeneous in demyelinating CMTs.
      SIGNIFICANCE: Nerve HRUS may separate CMT1A from other demyelinating CMTs. The
      large demyelinating CMTs HRUS spectrum may be related to its pathophysiological
      variability.

PMID- 30216911
TI  - Auditory gamma oscillations predict global symptomatic outcome in the early
      stages of psychosis: A longitudinal investigation.
AB  - OBJECTIVES: The gamma-band auditory steady-state response (ASSR) is thought to
      reflect the function of parvalbumin-positive gamma-aminobutyric acid (GABA)-ergic
      interneurons and may be a candidate biomarker in early psychosis. Although
      previous cross-sectional studies have shown that gamma-band ASSR is reduced in
      early psychosis, whether reduced gamma-band ASSR could be a predictor of the long
      term prognosis remains unknown. METHODS: In this longitudinal study, we
      investigated the association between gamma-band ASSR reduction and future global
      symptomatic or functional outcome in early psychosis. We measured 40-Hz ASSR in
      34 patients with recent-onset schizophrenia (ROSZ), 28 ultra-high risk (UHR)
      individuals, and 30 healthy controls (HCs) at baseline. After 1-2 years, we
      evaluated the global assessment of functioning (GAF) in the ROSZ (N = 20) and UHR
      (N = 20) groups. RESULTS: The 40-Hz ASSR was significantly reduced in the ROSZ
      and UHR groups. The attenuated 40-Hz ASSR was correlated with the future global
      symptomatic outcome in the ROSZ, but not in the UHR groups. CONCLUSIONS: A
      reduction in the gamma-band ASSR after the onset of psychosis may predict
      symptomatic outcomes in early psychosis. SIGNIFICANCE: Gamma-band ASSR may be a
      potentially useful biomarker of the long-term prognosis in patients with recent
      onset schizophrenia.

PMID- 30216912
TI  - Match probabilities for Y-chromosomal profiles: A paradigm shift.
AB  - Calculating match probabilities for genetic profiles under the hypothesis that a
      person of interest (henceforth the 'suspect') is not the donor of a particular
      forensic trace is challenging because the reference population is usually not
      clear-defined in such cases. Hence, the concept of 'suspect population' was
      introduced to allow for the fact that possible alternative trace donors often
      resemble the suspect in terms of their geographic, ethnic and social affiliation.
      In fact, they may even be genetically related to the suspect. Although the
      possibility of relatedness affects the size of the match probability in general,
      this is not a practically relevant issue for autosomal profiles owing to the
      stochastic independence of the markers included. The situation is, however,
      different for Y-chromosomal short tandem repeat (STR) profiles. Here, almost all
      profile matches are likely to be identical by descent, and profile identity may
      be common even among distantly related males. The degree of relatedness between
      suspect and alternative trace donors is thus a critical aspect of the evaluation
      of Y-chromosomal STR profile matches. All methods hitherto proposed to derive
      match probabilities for such cases, including our own, were anti-conservative in
      that they equated the suspect population to a database population (of virtually
      unrelated individuals). The nature of the true suspect population, however, is
      usually unknown and hard, if not impossible, to determine so that calculation of
      proper match probabilities remains a difficult task. Therefore, since lower Y
      chromosomal match probabilities would result from higher mutation rates, even for
      close relatives, future research should rather focus upon the characterization of
      novel and more mutable Y-chromosomal STRs.

PMID- 30216913
TI  - Parent-rating vs performance-based working memory measures: Association with
      spoken language measures in school-age children.
AB  - Working memory (WM) assessment is often part of cognitive-linguistic test
      batteries. The author examined the relationship between parent rating of WM
      functioning and children's performance-based WM, and the relationship of each
      with receptive and expressive spoken language measures. Study participants were
      eighty-three 7- to 11-year-old children. The sample represented a broad range of
      cognitive abilities. No participating child had frank neurological or
      intellectual disabilities, autism, fluency disorder, or hearing loss. Parents
      completed a standardized executive function rating scale that included a WM
      subscale. Children completed a standardized WM task and an experimental WM task.
      Children also completed six standardized language measures. Results showed that
      there was no correlation between parent rating and either of the performance
      based WM tasks as well as the composite WM performance score. Parent rating of WM
      functioning was not related to any of the language scores whereas the composite
      WM performance score showed significant links with language abilities. Although
      parent rating and performance-based WM measures are designed to reflect the same
      cognitive construct, they are not correlated. Potential reasons for the findings
      and implications of using parent-rating and performance-based WM measures in
      school-age children are discussed.

PMID- 30216914
TI  - Association between body mass index and clinical outcomes after new-generation
      drug-eluting stent implantation: Korean multi-center registry data.
AB  - BACKGROUND AND AIMS: It is unclear whether the obesity paradox is still apparent
      in the new-generation drug-eluting stent (DES) era. Therefore, we assessed the
      impact of body mass index (BMI) on clinical outcome after percutaneous coronary
      intervention (PCI) with new-generation DESs. METHODS: A total of 5264 consecutive
      patients from 4 new-generation DES registries were divided into 4 categories
      according to BMI: 1) underweight (BMI<18.5 kg/m2, n = 130), 2) normal weight
      (18.5 <= BMI <25 kg/m2, n = 2943), 3) overweight (25 <= BMI<30 kg/m2, n = 1932),
      and 4) obese (BMI>=30 kg/m2, n = 259). The primary endpoint was the occurrence of
      major adverse cardiac and cerebrovascular event (MACCE) at 12 months, including
      all-cause mortality, nonfatal myocardial infarction, stroke, and target-vessel
      revascularization. RESULTS: The 12-month MACCE rates decreased according to
      increasing BMI categories. (underweight, 13.1%; normal, 6.0%; overweight, 4.8%;
      obese, 4.2%; p < 0.001). After adjustment for other confounders, the underweight
      group had significantly higher MACCE rates than the normal-weight (hazard ratio
      [HR], 0.57; 95% confidence interval [CI], 0.33-0.99; p = 0.049), overweight (HR,
      0.49; 95% CI, 0.27-0.88; p = 0.017), and obese (HR, 0.41; 95% CI, 0.18-0.98; p =
      0.044) groups. These differences were mainly driven by all-cause mortality and
      target-vessel revascularization. When BMI was treated as a continuous variable,
      BMI per 1 kg/m2 was also an independent predictor for MACCE (HR, 0.95; 95% CI,
      0.91-0.99; p = 0.008) and a MACE increase began below a BMI of 24 kg/m2.
      CONCLUSIONS: Lower BMI was significantly associated with higher rates of MACCE
      and all-cause mortality after PCI. The obesity paradox is manifested in Korean
      patients in the new-generation DES era.

PMID- 30216915
TI  - Dietary patterns derived by factor analysis are associated with cognitive
      function among a middle-aged and elder Chinese population.
AB  - The aim of this study was to assess the association of empirically derived
      dietary patterns with cognitive function among a middle-aged and elder Chinese
      population. This study comprised 1676 Chinese adults >=45 years of age, who
      participated in a Health Survey and completed semi-quantitative food frequency
      questionnaire (FFQ) and cognitive screening test in the city of Linyi.We
      performed factor analysis using the principal component analysis method to
      identify the major dietary patterns. Binary logistic regression models were used
      to estimate odds ratio(OR) and 95% confidence interval(CI) for cognitive
      impairment according to quartiles of each dietary pattern score. Three dietary
      patterns were identified, namely traditional Chinese, Western-style and grains
      fruits-vegetable patterns. A total of 362 participants (101 men and 261 women)
      were classified as cognitive impaired. After controlling for potential
      confounders, participants in the highest quartile of the Western-style pattern
      had a greater OR for incident cognitive impairment, compared to participants in
      the lowest quartile. Compared with the lowest quartile of grains-fruits-vegetable
      pattern, the highest quartile had a lower OR for incident cognitive impairment.
      Conclusions: Our findings demonstrate that the Western-style pattern is
      associated with an elevated risk and the grains-fruits-vegetables pattern is
      associated with a decreased risk of cognitive impairment.

PMID- 30216916
TI  - Ketamine ameliorates depressive-like behaviors by tPA-mediated conversion of
      proBDNF to mBDNF in the hippocampus of stressed rats.
AB  - Some studies have indicated that ketamine has a rapid antidepressant effects, but
      the underlying molecular mechanism is still unclear. Researchers have found that
      mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF are
      related to depression; they elicit opposite effects on cellular functions. It is
      clear that tissue plasminogen activator (tPA) is a key regulatory element in the
      conversion of proBDNF to mBDNF. The chronic unpredicted mild stress (CUMS)
      procedure is a classical and reliable method to establish the model of
      depression. This study found that sucrose preference and locomotor activity were
      both reduced in CUMS-treated rats while were increased in those who were injected
      with ketamine. The hippocampal proBDNF/mBDNF ratio was downregulated after
      ketamine treatment in those rats, together with an increased level of tPA in the
      hippocampus. However, tPA activity was unaltered after ketamine intraperitoneal
      injection. Intrahippocampal injection of active plasminogen activator inhibitor-1
      (inhibitor of tPA) before ketamine treatment reversed the antidepressant effects
      and upregulated the proBDNF/mBDNF ratio. The results of this study suggest that
      the antidepressant action induced by ketamine may be related to tPA-mediated
      conversion of proBDNF to mBDNF in the hippocampus.

PMID- 30216917
TI  - Dissecting genetic cross-talk between ADHD and other neurodevelopmental
      disorders: Evidence from behavioural, pharmacological and brain imaging
      investigations.
AB  - Several epidemiological and genetic studies have provided evidence of an overlap
      between neurodevelopmental disorders. However, the details of the etiological
      pathways remain to be elucidated. In this study, we garnered the findings of
      previous GWAS, conducted with schizophrenia and bipolar disorder. We conducted an
      exploratory study to examine the association between these SNPs and quantitative
      clinical/ behavioural/ cognitive/ structural brain parameters, as well as
      response to treatment with a fixed dose of methylphenidate, in a relatively large
      sample of children with ADHD. Family-based association tests were conducted with
      nine tag SNPs with 602 nuclear families. In addition, structural magnetic
      resonance imaging (sMRI) was conducted in a subset of children with ADHD (n =
      76). Of the 9 tag SNPs examined, rs1602565 showed a significant association with
      ADHD, several dimensional measures and response to treatment. An association was
      also observed between rs1006737 (CACNA1C) and performance IQ. In addition,
      significant reductions in cortical thickness measurements were observed with the
      risk allele in rs1006737. These results provide preliminary evidence for putative
      shared genetic vulnerability between childhood ADHD and other neurodevelopmental
      disorders.

PMID- 30216918
TI  - The identification of biomarkers predicting acute and maintenance lithium
      treatment response in bipolar disorder: A plea for further research attention.
AB  - The prediction of acute and maintenance lithium treatment response carries major
      clinical and neurobiological implications, warranting systematic review. A
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      compliant review searched major electronic databases from inception until
      December 2017 for studies documenting a clinical diagnosis of bipolar disorder
      (BD) made according to the mainstream diagnostic manuals and confirmed by a
      structured interview. Eligible studies allowed a quantitative comparison of
      endpoint vs baseline mean values of a given biomarker, regardless of the mood
      phase of patients with BD, and the disorder was assessed for severity using
      validated rating tool(s). Owing to the purposely applied stringent selection
      criteria, 16 acute and 12 maintenance studies could be included. The anticipated
      publication bias limited the chances of reportable generalizable findings,
      hindering a side-by-side comparison of different records across varying
      biomarkers and subsequent meta-analyses. The PRISMA approach was nonetheless
      preferred; it aimed at enhancing the homogeneity of the included results and
      minimizing the chances of "apples and oranges" with respect to the present
      research theme. The present critical review confirms the need for future research
      to specifically assess either pretreatment and/or posttreatment putative
      biomarkers of patients with BD and treated with lithium.

PMID- 30216919
TI  - Insomnia, negative affect, and psychotic experiences: Modelling pathways over
      time in a clinical observational study.
AB  - Insomnia has been shown to contribute to the development of psychotic
      experiences, predominantly via increasing negative affect. However, the role of
      insomnia in the persistence of psychotic experiences is yet to be investigated in
      a clinical population. Furthermore, other plausible influences, such as psychotic
      experiences contributing to insomnia, remain to be evaluated. This study tests
      the role of insomnia as a predictor of persistence of psychotic experiences
      versus other potential causal routes. Twenty-nine patients aged 18-30 with non
      affective psychosis completed three assessments over three months of their
      insomnia, negative affect, and psychotic experiences. Mixed effect models allowed
      comparisons between hypothesis-based models (comprising insomnia as predictor,
      negative affect as mediator, and psychotic experiences as outcome) and
      oppositional models, where relationships were reversed. The results supported the
      hypothesised mediation model above models where negative affect was primary.
      Insomnia was also found to be a stronger predictor of later hallucinations than
      vice versa, although a bidirectional relationship was indicated between insomnia
      and paranoia. In conclusion, insomnia predicts persistence of psychotic
      experiences over time to the same or greater extent than psychotic experiences
      contribute to insomnia. This supports insomnia as a potential intervention target
      in psychosis.

PMID- 30216921
TI  - Coal chemical reverse osmosis concentrate treatment by membrane-aerated biofilm
      reactor system.
AB  - Coal chemical reverse osmosis concentrate (ROC), which is characterized by high
      salinity and high organics, remains as a serious environmental problem. In this
      study, a lab-scale three-stage membrane-aerated biofilm reactor (MABR) system was
      designed to treat such a ROC. The effects of influent salinity and operating
      parameters (pH, DO and HRT) on the treatment efficiency were discussed. The
      removal efficiencies of COD, NH4-N and TN under the optimal operating parameters
      reached to 81.01%, 92.31% and 70.72%, respectively. Simultaneous nitrification
      and denitrification (SND) as well as shortcut nitrogen removal were achieved. The
      salinity less than 3% did not induce significant decrease in treatment efficiency
      and microbial communities. Moreover, the dominant phyla in biofilms were
      Proteobacteria and Bacteroidetes. This work demonstrated MABR had great potential
      in ROC treatment.

PMID- 30216920
TI  - Suppression of membrane fouling in the ceramic membrane bioreactor (CMBR) by
      minute electric field.
AB  - Three ceramic MBRs (CMBR) installed with varied electrodes, i.e. Cu, Ti and Fe,
      were operated in parallel under the minute electric field to evaluate their
      suppression effect on membrane fouling, by comparison with control CMBR. Fe-CMBR
      released Fe2+ continuously to induce a higher organic removal efficiency and a
      smooth fouling rate. There was significant electric-flocculation effect in the Fe
      CMBR, reflected by the increased sludge particle size and zeta potential, and to
      improve sludge filterability. Application of minute electric field could also
      affect the CMBR supernatant organic content and components, which was another
      reason for fouling mitigation. The formed membrane fouling layer was more easily
      to be detached by simple backwashing in all electric CMBRs, since that there were
      significant electric repulsive force to prevent foulants deposition.

PMID- 30216923
TI  - Energy balance and life cycle assessment of a microalgae-based wastewater
      treatment plant: A focus on alternative biogas uses.
AB  - The techno-environmental performance of a medium-scale wastewater treatment
      system using high-rate algal ponds was evaluated through mass and energy balances
      and life cycle assessment. The system involves wastewater primary treatment,
      microalgae-based secondary treatment, thermal hydrolysis with steam explosion of
      microalgae, anaerobic co-digestion of pre-treated microalgal biomass and primary
      sludge, and biogas cogeneration. Furthermore, two scenarios based on alternative
      biogas uses were considered: (i) biogas for heat and electricity, and (ii) biogas
      for heat, electricity, and biomethane. Pumping wastewater to the primary settler
      arose as the main source of electricity consumption. When compared to
      conventional activated sludge plants, a large decrease in the energy consumption
      was observed for the secondary treatment. Moreover, a favourable life-cycle
      performance was generally found for the microalgae-based systems when displacing
      conventional energy products. Finally, the preference for a specific scenario on
      biogas use was found to be highly conditioned by the techno-environmental aspects
      prioritised by decision-makers.

PMID- 30216922
TI  - Effect of acidic, neutral and alkaline conditions on product distribution and
      biocrude oil chemistry from hydrothermal liquefaction of microalgae.
AB  - Hydrothermal liquefaction (HTL) of microalgae produces high amount of water
      insoluble organic compounds, the biocrude oil. Using high-growth-rate Spirulina
      platensis as feedstock, product fraction distribution and biocrude oil chemistry
      from HTL at a temperature of 240-300  degrees C under acidic, neutral and
      alkaline condition were studied. Positive effects on biocrude oil yield were only
      found with KOH and acetic acid, and these effects were stronger under milder HTL
      conditions. FT-ICR MS showed that O2 class in the biocrude was high due to higher
      carbohydrate in the biomass, numbers of N3O5-6 species present in the sample from
      acetic acid run, indicating its less decarboxylation ability. GC-MS showed more
      ketones and amides were formed from fatty acids in catalytic HTL, and this effect
      was sensitive toward reaction temperature. GPC suggested more light volatiles
      were in biocrude from KOH run, while analysis from NMR, FT-IR and elemental
      confirmed its high oil quality.

PMID- 30216924
TI  - Efficiency, granulation, and bacterial populations related to pollutant removal
      in an upflow microaerobic sludge reactor treating wastewater with low COD/TN
      ratio.
AB  - In this study, a novel upflow microaerobic sludge reactor (UMSR) was constructed
      to conduct anaerobic digestion of municipal wastewater with low carbon and
      nitrogen ratio (C/N). Oxygen in the UMSR was supplied by falling water and
      external recirculation. Excellent nitrogen removal performance was obtained in
      the UMSR for treating wastewater with low C/N ratio at a temperature of 25 
      degrees C and a hydraulic retention time of 24 h. Ammonium and total nitrogen
      removal efficiencies averaged 92.35% and 90.41%, respectively, and sludge
      granulation occurred during acclimation. The inferred metabolism of nitrogen
      removal and ecological positions of functional microbe were integrated into a
      granule model by scanning electron microscopy. Additionally, the analysis of
      microbial community indicated that aerobic nitrifying bacteria and heterotrophic
      bacteria survived on the surface of sludge floc and granules while the anaerobic
      autotrophic, heterotrophic denitrifying, and anaerobic ammonia oxidation bacteria
      were present in the inner layer.

PMID- 30216926
TI  - Endoscopic excision of hydatid cyst: A case of delayed anaphylaxis in
      postoperative period - "The risk is not over until it is over".

PMID- 30216925
TI  - Neuraxial morphine after unintentional dural puncture is not associated with
      reduced postdural puncture headache in obstetric patients.
AB  - STUDY OBJECTIVE: To examine the relationship between neuraxial morphine exposure
      after unintentional dural puncture and the risk for postdural puncture headache
      in obstetric patients. DESIGN: Retrospective cohort study. SETTING: Obstetrical
      unit at a tertiary care referral center. PATIENTS: Parturients receiving labor
      epidural analgesia with recognized unintentional dural puncture. INTERVENTIONS:
      Cases in which neuraxial morphine was given for any reason were compared to cases
      in which it was not for the outcome of postdural puncture headache. MEASUREMENTS:
      Development of postdural puncture headache, headache severity, number of epidural
      blood patches, hospital length of stay. MAIN RESULTS: Of the 80 cases that were
      included, 38 women received neuraxial morphine and 42 did not. There was no
      significant difference in the incidence of headache between the two morphine
      groups (Headache present: Morphine: 27/56 [48.2%], No morphine: 29/56 [51.8%];
      Headache free: Morphine: 11/24 [45.8%], No morphine: 13/24 [54.2%], P = 0.84).
      There was no difference in the need for epidural blood patch (Morphine: 24/42
      [57.1%], No morphine: 18/38 [47.4%], P = 0.50) and headache severity (mean
      headache pain score: Morphine: 7.9 +/- 1.8 vs. No morphine: 7.3 +/- 2.4, P =
      0.58). Hospital length of stay was higher in the morphine group (4.4 +/- 2.9 days
      vs. 3.0 +/- 1.5 days respectively, P = 0.008). Using logistic regression,
      morphine did not affect headache risk after controlling for covariates (morphine
      vs. no morphine: adjusted OR 1.24 [0.75]; P = 0.72; pre-eclampsia vs. no pre
      eclampsia: adjusted OR 0.56 [0.41], P = 0.42; cesarean vs. normal spontaneous
      vaginal delivery: adjusted OR 0.97 [0.67]; P = 0.96). CONCLUSION: In cases of
      unintentional dural puncture, exposure to neuraxial morphine for any reason may
      not be protective against the risk of postdural puncture headache. Although an
      overall protective effect of neuraxial morphine was not observed in this study,
      its role in specific subsets of patients remains to be investigated.

PMID- 30216927
TI  - Opioid-free total intravenous anesthesia with ketamine as part of an enhanced
      recovery protocol for bariatric surgery patients with sleep disordered breathing.

PMID- 30216928
TI  - Management of dural puncture headache caused by caudal epidural steroid
      injection.

PMID- 30216930
TI  - Effects of compression on orientation of ligands in fluorescent complexes between
      hydroxyapatite with amino acids and their optical properties.
AB  - This study aims to reveal the effects of pressure during cold isostatic pressing
      (CIP) on the microstructure and optical properties of fluorescent HAp complexes.
      Although the microsturucture-dependent properties of fluorescent HAp complexes
      have been reported to improve the antibacterial properties of photocatalyst
      coating layers, the mechanism behind the changes in the fluorescence properties
      of highly compressed HAp complexes has not yet been unveiled. CIP was
      successfully used to fabricate fluorescent HAp - amino acid complexes, and their
      fluorescence intensities increased with increasing fabrication pressure. Peak
      wavelength of fluorescence emitted by the HAp - amino acid complexes exhibited
      yellow to red shift. Although the thickness of the amino acid layer was saturated
      in higher pressure cases, the concentration of amino acids increased
      proportionally with pressure, which suggests changes in the packing structures of
      the ligands in the HAp- amino acid complexes. Polarized Raman spectroscopy
      measurements clearly detected ligands normally arranged to the HAp layer under
      high pressure fabrication conditions, which can provide the tightly packed ligand
      structure in the HAp- amino acid complexes. These tightly packed ligand structure
      in the HAp- amino acid complexes could emit stronger fluorescence owing to the
      increased density of complexations. This newly found pressure dependency in the
      optical properties of HAp-amino acid complexes is beneficial for developing
      biocompatible fluorescence materials or enhancement agents for antibacterial
      coating layers.

PMID- 30216931
TI  - Atomic force microscopy measurements probing the mechanical properties of single
      collagen fibrils under the influence of UV light in situ.
AB  - Collagen plays a decisive role as a functional substrate in tissue engineering.
      In particular, the rigidity of the collagen influences the behaviour of the
      attached cells. Thus, modification and controlled adjustment of collagen's
      characteristics are essential. To this end, controlled exposure to ultraviolet
      (UV) light is a promising process because it can be temporally and spatially well
      defined. In this study, we investigated the effect of UV exposure on surface
      supported single collagen fibrils in situ. This procedure allowed for a direct
      comparison between the untreated and modified states of type I collagen. Atomic
      force microscopy was used to map the mechanical properties. Exposure to UV light
      was used to influence the mechanical properties of the fibrils in varied liquid
      environments (deionized water and phosphate-buffered saline (PBS)). The results
      led to the assumption that combined UV/thermal treatment in deionized water
      continuously lowers the elastic modulus. In contrast, experiments performed in
      PBS-based solutions in combination with UV-B and UV-C light or thermal treatment
      up to 45  degrees C suggested an increase in the modulus within the first 30-40
      min that subsequently decreased again. Thus, the wavelength, exposure,
      temperature, and chemical environment are relevant parameters that need to be
      controlled when modifying collagen using UV light.

PMID- 30216929
TI  - Ripple oscillations in the left temporal neocortex are associated with impaired
      verbal episodic memory encoding.
AB  - BACKGROUND: We sought to determine if ripple oscillations (80-120 Hz), detected
      in intracranial electroencephalogram (iEEG) recordings of patients with epilepsy,
      correlate with an enhancement or disruption of verbal episodic memory encoding.
      METHODS: We defined ripple and spike events in depth iEEG recordings during list
      learning in 107 patients with focal epilepsy. We used logistic regression models
      (LRMs) to investigate the relationship between the occurrence of ripple and spike
      events during word presentation and the odds of successful word recall following
      a distractor epoch and included the seizure onset zone (SOZ) as a covariate in
      the LRMs. RESULTS: We detected events during 58,312 word presentation trials from
      7630 unique electrode sites. The probability of ripple on spike (RonS) events was
      increased in the SOZ (p < 0.04). In the left temporal neocortex, RonS events
      during word presentation corresponded with a decrease in the odds ratio (OR) of
      successful recall, however, this effect only met significance in the SOZ (OR of
      word recall: 0.71, 95% confidence interval (CI): 0.59-0.85, n = 158 events,
      adaptive Hochberg, p < 0.01). Ripple on oscillation (RonO) events that occurred
      in the left temporal neocortex non-SOZ also correlated with decreased odds of
      successful recall (OR: 0.52, 95% CI: 0.34-0.80, n = 140, adaptive Hochberg, p <
      0.01). Spikes and RonS that occurred during word presentation in the left middle
      temporal gyrus (MTG) correlated with the most significant decrease in the odds of
      successful recall, irrespective of the location of the SOZ (adaptive Hochberg, p
      < 0.01). CONCLUSION: Ripples and spikes generated in the left temporal neocortex
      are associated with impaired verbal episodic memory encoding. Although
      physiological and pathological ripple oscillations were not distinguished during
      cognitive tasks, our results show an association of undifferentiated ripples with
      impaired encoding. The effect was sometimes specific to regions outside the SOZ,
      suggesting that widespread effects of epilepsy outside the SOZ may contribute to
      cognitive impairment.

PMID- 30216933
TI  - Experimental reconstruction of an abdominal wall defect with electrospun
      polycaprolactone-ureidopyrimidinone mesh conserves compliance yet may have
      insufficient strength.
AB  - PURPOSE: Electrospun meshes mimic the extracellular matrix, which may improve
      their integration. We aimed to compare polycaprolactone (PCL) modified with
      ureidopyrimidinone (UPy) electrospun meshes with ultra-lightweight polypropylene
      (PP; Restorelle) reference textile meshes for in vivo compliance. We chose UPy
      PCL because we have shown it does not compromise biomechanical properties of
      native tissue, and because it potentially can be bioactivated. METHODS: We
      performed ex vivo biomechanical cyclic loading in wet conditions and in vivo
      overlay of full-thickness abdominal wall defects in rats and rabbits. Animals
      were sacrificed at 7, 42 and 54 days (rats; n = 6/group) and 30 and 90 days
      (rabbits; n = 3/group). Outcomes were herniation, mesh degradation and mesh
      dimensions, explant compliance and histology. High failure rates prompted us to
      provide additional material strength by increasing fiber diameter and mesh
      thickness, which was further tested in rabbits as a biomechanically more
      challenging model. RESULTS: Compliance was tested in animals without herniation.
      In both species, UPy-PCL-explants were as compliant as native tissue. In rats, PP
      explants were stiffer. Contraction was similar in UPy-PCL and PP-explants.
      However, UPy-PCL-meshes macroscopically degraded from 30 days onwards, coinciding
      with herniation in up to half of animals. Increased fiber and mesh thickness did
      not improve outcome. Degradation of UPy-PCL is associated with an abundance of
      foreign body giant cells until UPy-PCL disappears. CONCLUSION: Abdominal wall
      reconstruction with electrospun UPy-PCL meshes failed in 50%. Degradation
      coincided with a transient vigorous foreign body reaction. Non-failing UPy-PCL
      explants were as compliant as native tissue. Despite that, the high failure rate
      forces us to explore electrospun meshes based on other polymers.

PMID- 30216932
TI  - Synthesis and characterization of bio-compatible shape memory polymers with
      potential applications to endovascular embolization of intracranial aneurysms.
AB  - Intracranial aneurysms (ICAs) are focal dilations in the brain's arteries. When
      left untreated, ICAs can grow to the point of rupture, accounting for 50-80% of
      subarachnoid hemorrhage cases. Current treatments include surgical clipping and
      endovascular coil embolization to block circulation into the aneurysmal space for
      preventing aneurysm rupture. As for endovascular embolization, patients could
      experience aneurysm recurrence due to an incomplete coil filling or compaction
      over time. The use of shape memory polymers (SMPs) in place of conventional
      platinum coils could provide more control and predictability for mitigating these
      complications. This study was focused on characterization of an aliphatic
      urethane-based SMP to evaluate its potential as a novel biomaterial for
      endovascular embolization. Twelve compositions of the SMP were synthesized and
      their thermomechanical properties together with the shape recovery behavior were
      comprehensively investigated. Our results showed that the SMPs experienced a
      significant decrease in storage and loss moduli as heated above their glass
      transition temperatures (32.3-83.2  degrees C), and that all SMPs were thermally
      stable up to 265  degrees C. Moreover, the SMPs exhibited both composition
      dependent stress relaxation and a decrease in elastic modulus during cyclic
      loading. The shape recovery time was less than 11 s for all SMP compositions,
      which is sufficiently short for shape changing during embolization procedures.
      Several candidate compositions were identified, which possess a glass transition
      temperature above body temperature (37  degrees C) and below the threshold of
      causing tissue damage (45  degrees C). They also exhibit high material strength
      and low stress relaxation behavior, suggesting their potential applicability to
      endovascular embolization of ICAs.

PMID- 30216934
TI  - Patients with small-vessel vasculitides have the highest mortality among systemic
      autoimmune diseases patients treated in intensive care unit: A retrospective
      study with 5-year follow-up.
AB  - PURPOSE: Systemic autoimmune diseases are a heterogeneous group of disorders
      associated with dysfunction of multiple organs and unpredictable course.
      Complicated management and treatment become even more challenging when patients
      require critical care. This study aims to compare outcomes of small-vessel
      vasculitides (SVV) and other systemic autoimmune diseases (SAD) patients admitted
      to the intensive care unit (ICU). MATERIALS AND METHODS: Retrospective,
      observational study conducted in the ICU of Allergy and Immunology Department at
      the University Hospital in Krakow, Poland, between years 2001-2014, with 5-years
      follow-up and no lost to follow-up patients. RESULTS: 74 patients with autoimmune
      diseases were enrolled in the study - 23 with SVV and 51 with SAD. Patients in
      the SVV group achieved higher scores in APACHE II and III SAPS II and SOFA at ICU
      admission. The SVV patients required renal replacement techniques, blood products
      transfusion and immunosuppressive treatment more often. SVV patients had higher
      ICU mortality (60.9% vs. 35.3%, p = .04), however after discharge from ICU, in
      long term follow-up (1 year and 5 years) mortality was similar in both studied
      groups. CONCLUSIONS: Among systemic autoimmune diseases small vessel vasculitides
      appear to be associated with the highest ICU mortality, higher requirement for
      advanced procedures and aggressive immunosuppressive therapy.

PMID- 30216935
TI  - Clinical characteristics, evolution, and treatment-related risk factors for
      mortality among immunosuppressed patients with influenza A (H1N1) virus admitted
      to the intensive care unit.
AB  - PURPOSE: Information about immunocompromised patients infected with influenza A
      (H1N1) virus and requiring admission to the ICU is lacking. Our objective was to
      know the clinical characteristics of these patients and to identify treatment
      related variables associated with mortality. MATERIAL AND METHODS: A prospective
      multicenter observational cohort study was based on data from a Spanish registry
      (2009-2015) collected by 148 Spanish ICUs. All patients admitted to the ICU with
      the diagnosis of influenza A (H1N1) virus infection were included.
      Immunosuppression was clearly defined. Factors associated with mortality in
      immunocompromised patients were assessed by conventional logistic regression
      analysis and by a propensity score (PS) adjusted-multivariable analysis. RESULTS:
      Of 1899 patients with influenza A (H1N1) infection, 238 (12.5%) were classified
      as immunocompromised. Mortality was significantly higher in immunosuppressed
      patients. Four variables independently associated with mortality were identified:
      SOFA score, need of vasopressor, use of corticosteroids, and acute renal failure,
      AKIN 3 stage. In the PS-adjusted model, corticosteroid therapy remained as an
      independent factor associated with increased mortality (OR 2.25;95%CI, 1.15
      4.38;p = 0.017). In the subgroup of hematological patients (n = 141),
      corticosteroid therapy was also associated with increased mortality (OR 3.12;
      95%CI, 1.32-7.41; p = 0.010). CONCLUSION: Immunocompromised individuals with
      influenza A (H1N1) admitted to the ICU have a poor outcome. In this population,
      the use of corticosteroids is strongly discouraged.

PMID- 30216937
TI  - Acute promyelocytic leukemia in the intensive care unit: A retrospective
      analysis.

PMID- 30216936
TI  - The Italian law on informed consent and advance directives: New rules of conduct
      for the autonomy of doctors and patients in end-of-life care.
AB  - PURPOSE: Italy has long lacked a law regulating patients' informed consent and
      advance directives (ADs). All previous attempts to introduce a law on this matter
      failed to reach positive outcomes, and aroused heated ideological debate over the
      exact meaning of life and death. We report on the new law on informed consent and
      ADs approved by the Italian Parliament on 14th December 2017. MATERIALS AND
      METHODS: We analyse the new law and discuss the main ethical points connected
      with it, in the Italian context and in comparison with the international
      situation. RESULTS: The law provides for fundamental ethical principles and
      important guidelines: respect for patients' self-determination in all phases of
      life, option to refuse or interrupt life-sustaining treatments, including
      artificial nutrition and hydration, the legitimacy of end-of-life decisions, and
      the implementation of palliative care to ease suffering and pain. CONCLUSIONS:
      The effects of the new law must be tested in the field. Its objectives will be
      achieved if, in clinical practice, ADs are able to satisfactorily represent
      informed personal preferences through patients' relationships with their
      physicians, as part of personalized advance care planning. Future studies are
      necessary to assess the impact of the new law in Italy.

PMID- 30216938
TI  - Association between health literacy, communication and psychological distress
      among myelodysplastic syndromes patients.
AB  - MDS is a complex and potentially severe disease which can trigger psychological
      distress. A lack of information received and understood about MDS may also arouse
      feelings of distress. Low health literacy (HL) might play a role particularly
      among older patients. Our aim was to assess MDS-related distress and to study the
      factors associated with it, including medical and non-medical factors such as HL.
      A self-administered questionnaire was mailed to all members of French and
      Australian patients' national MDS associations. Data of 280 patients were
      analysed. A majority of patient (59.5%) reported low functional HL and 50%
      reported regular difficulties in asking physicians questions. Distress was not
      modified by gender, awareness of increased risk of developing leukaemia or MDS
      characteristics. French patients had a higher mean IES score (adjusted beta =
      5.9, p = 0.004) compared to Australian patients. Poor satisfaction with
      information provided about MDS, lower functional HL and difficulties in asking
      physician's questions were also independently associated with distress. MDS
      related distress seems more related to HL and communication with physicians than
      to MDS characteristics. More efforts are needed to improve health literacy,
      tailor information for MDS patients and support them psychologically in order to
      improve their emotional well-being.

PMID- 30216939
TI  - Paradoxical effects of mutant ubiquitin on Abeta plaque formation in an Alzheimer
      mouse model.
AB  - Amyloid-beta (Abeta) plaques are a prominent pathological hallmark of Alzheimer's
      disease (AD). They consist of aggregated Abeta peptides, which are generated
      through sequential proteolytic processing of the transmembrane protein amyloid
      precursor protein (APP) and several Abeta-associated factors. Efficient clearance
      of Abeta from the brain is thought to be important to prevent the development and
      progression of AD. The ubiquitin-proteasome system (UPS) is one of the major
      pathways for protein breakdown in cells and it has been suggested that impaired
      UPS-mediated removal of protein aggregates could play an important role in the
      pathogenesis of AD. To study the effects of an impaired UPS on Abeta pathology in
      vivo, transgenic APPSwe/PS1DeltaE9 mice (APPPS1) were crossed with transgenic
      mice expressing mutant ubiquitin (UBB+1), a protein-based inhibitor of the UPS.
      Surprisingly, the APPPS1/UBB+1 crossbreed showed a remarkable decrease in Abeta
      plaque load during aging. Further analysis showed that UBB+1 expression
      transiently restored PS1-NTF expression and gamma-secretase activity in APPPS1
      mice. Concurrently, UBB+1 decreased levels of beta-APP-CTF, which is a gamma
      secretase substrate. Although UBB+1 reduced Abeta pathology in APPPS1 mice, it
      did not improve the behavioral deficits in these animals.

PMID- 30216940
TI  - How we resect colorectal polyps < 20 mm in size.

PMID- 30216943
TI  - Multimodality Imaging for Navigation in Endoscopic Transsphenoidal Surgeries.
AB  - BACKGROUND AND STUDY AIMS:  Computed tomography (CT) and magnetic resonance image
      (MRI) data have been widely used to for navigation in various neurosurgical
      operations. However, delicate intracranial structures cannot be displayed using
      only one imaging method. Navigation with multimodality imaging was developed to
      better visualize these structures in glioma removal, but whether it is useful in
      endoscopic transsphenoidal surgery is unknown. We describe our clinical
      experience using multimodality imaging for navigation in endoscopic
      transsphenoidal surgeries. MATERIAL AND METHODS:  A total of 134 patients
      underwent endoscopic transsphenoidal surgery with navigation using multimodality
      imaging. CT and MR images were fused and processed to optimally visualize
      anatomical structures of the sphenoidal sinus and tumor. RESULTS:  Navigation
      with multimodality imaging offers a precise display of anatomical structures in
      the sphenoid sinus as compared with navigation based on either CT or MRI.
      CONCLUSION:  Navigation with multimodality imaging is capable of providing
      optimized guidance during endoscopic transsphenoidal surgeries. The fused images
      allow precise visualization of sphenoidal sinus structures, lesions and tumors.
      This is valuable for increasing safety in cases of anatomical variations and
      potentially decreasing the rate of tumor recurrence.

PMID- 30216941
TI  - Higher HbA1c Measurement Quality Standards are Needed for Follow-Up and
      Diagnosis: Experience and Analyses from Germany.
AB  - Measurement of HbA1c is an essential laboratory measure for the follow-up and
      therapy decision-making in patients with diabetes. HbA1c is one of the measurands
      in laboratory medicine that have to be successfully checked according to the
      criteria of the guidelines of the German Medical Association (Rili-BAEK) in
      external quality assurance using the reference method value concept, when applied
      in patient care. The allowed deviation of +/-18% in external quality assessment
      (EQA) and +/- 10% in internal quality control has been ultimately met by
      virtually all the different manufacturers and methods. However, such broad limits
      for permissible deviations are not suitable in view of medical requirements in
      patient care. The low-level acceptance criteria also depends on the previously
      used EQA materials used in Germany. In fact, HbA1c measurement results that are
      imprecisely measured or come from incorrectly calibrated devices are difficult to
      identify. With implementation of unprocessed fresh EDTA blood, the situation has
      changed. Until now systems with unit use reagents for point-of-care testing
      (POCT) of HbA1c are not mandatory to participate in EQA schemes in Germany. This
      paper outlines why there was a need to narrow the acceptance limits listed within
      the Rili-BAEK for HbA1c's internal (to +/- 3%) and external (to +/- 8%) quality
      controls in EQA schemes for Germany, which will take place after a transition
      period in the next years. Higher quality in HbA1c measurements will help to avoid
      misdiagnosis of diabetes as well as potential over- or undertreatment of patients
      at risk for diabetes.

PMID- 30216942
TI  - Targeted Gene Panel Sequencing for Molecular Diagnosis of Kallmann Syndrome and
      Normosmic Idiopathic Hypogonadotropic Hypogonadism.
AB  - BACKGROUND: Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is
      classified either as Kallmann syndrome (KS) with anosmia or normosmic idiopathic
      hypogonadotropic hypogonadism (nIHH) and caused by mutations in more than 30
      different genes. Recent advances in next-generation sequencing technologies have
      revolutionized the identification of causative genes by using massively parallel
      sequencing of multiple samples. This study was performed to establish the genetic
      etiology of IGD using a targeted gene panel sequencing of 69 known human IGD
      genes. METHODS: This study included 28 patients with IGD from 27 independent
      families. Exomes were captured using customized SureSelect kit (Agilent
      Technologies) and sequenced on the Miseq platform (Illumina, Inc.), which
      includes a 163,269 bp region spanning 69 genes. RESULTS: Four pathogenic and six
      likely pathogenic sequence variants were identified in 11 patients from 10 of the
      27 families (37%) included in the study. We identified two known pathogenic
      mutations in CHD7 and PROKR2 from two male patients (7.4%). Novel sequence
      variants were also identified in 10 probands (37%) in CHD7, SOX3, ANOS1, FGFR1,
      and TACR3. Of these, while eight variants (29.6%) were presumed to be pathogenic
      or likely pathogenic, the remaining two were classified as variants of uncertain
      significance. Of the two pre-pubertal males with anosmia, one harbored a novel
      heterozygous splice site variant in FGFR1. CONCLUSIONS: The overall diagnostic
      yield was 37% of the patients who had undergone targeted gene panel sequencing.
      This approach enables rapid, cost-effective, and comprehensive genetic screening
      in patients with KS and nIHH.

PMID- 30216944
TI  - [Clinical Outcomes after Keraring Implantation for Keratoconus Management in Thin
      Corneas].
AB  - BACKGROUND: The aim of our study was to evaluate the clinical outcomes after
      Keraring implantation for keratoconus in patients with thin corneas. PATIENTS AND
      METHODS: Ten eyes from 10 patients with keratoconus, who underwent femtosecond
      laser-assisted Keraring implantation for keratoconus, were included in this
      retrospective study. Uncorrected visual acuity (UCVA), corrected visual acuity
      (CDVA), keratometric readings, central corneal thickness and thinnest corneal
      pachymetry have been evaluated preoperatively and 6 months after the Keraring
      implantation. RESULTS: UCVA, BCVA and keratometric readings improved at 6 months
      postoperatively. CONCLUSIONS: Our data showed significant keratometric
      amelioration and visual improvement after Keraring implantation for keratoconus
      in patients with thin corneas at 6 months postoperatively.

PMID- 30216945
TI  - ?

PMID- 30216946
TI  - Tongue-in-Groove Technique for Rhinoplasty: Technical Refinements and
      Considerations.
AB  - A key concept in successful rhinoplasty surgery is maintaining or increasing tip
      support, and addressing tip projection and rotation. The tongue-in-groove (TIG)
      technique is a method to achieve this goal using sutures to create a strong
      connection between the septum and medial crura to change tip rotation and
      projection. Criticisms of this method include that it may cause stiffness of the
      nasal tip and columellar retraction. TIG is routinely used by the authors during
      anterior septal reconstructions (a modified extracorporeal septoplasty
      technique), as well as in primary and revision aesthetic and functional
      rhinoplasties. Through this review, technical aspects of the TIG technique are
      discussed, as well as how pitfalls of the technique can be avoided, as
      illustrated by several rhinoplasty patient examples.

PMID- 30216947
TI  - Change from Hybrid to Fully Minimally Invasive and Robotic Esophagectomy is
      Possible without Compromises.
AB  - BACKGROUND:  The incidence of esophageal carcinoma is increasing in the western
      world, and esophageal resection is the essential therapy. Several studies report
      advantages of minimally invasive esophagectomies (MIEs) versus conventional open
      procedures (OPs). The benefits of the use of fully MIE or robot-assisted MIE
      (RAMIE) compared with the hybrid approaches (laparoscopic gastric preparation and
      open transthoracic esophagectomy) remain unclear. METHODS:  Between July 2015 and
      August 2017, the data of 75 patients with esophageal carcinoma were prospectively
      registered. Of the 75 patients, 25 treated with a hybrid MIE (hybrid), 25 with
      total MIE (MIE), and 25 with RAMIE. All patients were operated by the same
      specialized surgeon in our center with an identical anastomotic technique
      (circular stapler). RESULTS:  The overall 30- and 90-day mortality rates were 0
      and 1.33% (1/75), respectively. Total hospital stay (p = 0.262), intensive care
      unit stay (p = 0.079), number of resected lymph nodes (p = 0.863), and R status
      (p = 0.132) did not differ statistically between the groups. However, pneumonia
      and wound infections occurred significantly and more frequently in the hybrid
      group compared with the minimally invasive groups (MIE and RAMIE) (p = 0.046 and
      p = 0.003, respectively). CONCLUSION:  Comparable results regarding morbidity and
      short-term outcome could be achieved in the MIE and RAMIE groups compared with
      the hybrid group. The data indicate that the learning curve is low in surgeons
      changing the technique form hybrid esophagectomy to fully MIE. Additionally, the
      total minimally invasive approaches seem to be associated with a low incidence of
      complications such as pneumonia and wound infections.

PMID- 30216948
TI  - Long-Term Results of Compressive Brace Therapy for Pectus Carinatum.
AB  - BACKGROUND:  Pectus carinatum (PC) is one of the most common types of congenital
      chest wall deformity. Recently, noninvasive compressive brace therapy has been
      more frequently used than invasive surgical correction to treat PC. Hence, the
      purpose of this study was to determine the long-term outcome of compressive brace
      therapy. METHODS:  We retrospectively reviewed patients with PC who underwent
      compressive brace therapy between January 2014 and December 2016. All patients
      underwent a 2-week compression period, in which braces were worn for 20 hours per
      day, followed by a 6-month maintenance period, in which braces were worn for 12
      hours per day. Patient satisfaction was investigated via telephone survey.
      RESULTS:  A total of 320 patients were included in this study. The average age
      was 13 years, and 280 were males (87.5%). The median follow-up period was 42
      months (13-68). Good compliance was observed in 286 patients (89.4%; compliance
      group). In this group, the initial Haller index significantly increased from 2.20
      +/- 0.31 to 2.59 +/- 0.38 after the 6-month therapy period (p = 0.001). After the
      6-month period, 255 patients (89.1%) and 31 patients (12.1%) in the compliance
      group were very satisfied and satisfied, respectively. Satisfaction at the last
      follow-up via telephone survey was very satisfied in 250 patients (87.4%) and
      satisfied in 36 (12.6%). In the compliance group, no patient needed compressive
      braces again after the therapy period. CONCLUSION:  Given the findings presented
      in this study, compressive brace therapy appears to be a relatively simple and
      safe method with good long-term outcome in treating patients with PC.

PMID- 30216949
TI  - CT-Guided Chemical Thoracic Sympathectomy versus Botulinum Toxin Type A Injection
      for Palmar Hyperhidrosis.
AB  - BACKGROUND:  The present study aimed to evaluate and compare the efficacy of
      botulinum toxin type A (BTX-A) injection versus thoracic sympathectomy for
      idiopathic palmar hyperhidrosis. METHODS:  Fifty-one patients with idiopathic
      palmar hyperhidrosis were treated with either BTX-A injection or thoracic
      sympathectomy between March 2013 and April 2016. The severity of palmar
      hyperhidrosis was qualitatively measured via the Hyperhidrosis Disease Severity
      Scale (HDSS). All patients completed a questionnaire that detailed the time taken
      for the treatment to work, local or systemic adverse effects, and pre- and post
      treatment severity of hyperhidrosis. The efficacy and adverse effects of the two
      treatments were compared and analyzed. RESULTS:  Hyperhidrosis-related quality of
      life improved quickly and significantly in the BTX-A group (26 patients) and the
      sympathectomy group (25 patients). Compared with pre-treatment, the HDSS score
      significantly reduced after treatment in both groups (p < 0.05). All patients in
      the sympathectomy group had cessation of sweating of the hands after treatment,
      and this curative effect lasted for 12 months. In contrast, the treatment took
      more time to work in the BTX-A group, and the curative effect lasted for a much
      shorter period (3 months). The sympathectomy group had a significantly lesser
      mean HDSS score than the BTX-A group at 1 week, 3 months, 6 months, 9 months, and
      12 months after treatment (p < 0.05). The sympathectomy group experienced more
      complications than the BTX-A group. CONCLUSION:  For palmar hyperhidrosis,
      thoracic sympathectomy is more effective and has a longer lasting curative effect
      than BTX-A injection, but thoracic sympathectomy has more complications.

PMID- 30216950
TI  - [Widefield Diagnostics of the Posterior Segment].

PMID- 30216951
TI  - [Peripheral Ischemia in Diabetic Retinopathy and Retinal Vein Occlusion: New
      Insights with Ultra-Wide-Angle Fundus Imaging and Wide-Angle Fluorescein
      Angiography].
AB  - BACKGROUND: In several diseases such as diabetic retinopathy and retinal vein
      occlusion, relevant pathophysiological changes take place in the retinal
      periphery. These changes may determine the prognosis and outcomes of therapy.
      Recent ultra-wide-angle camera systems promise improved and simplified
      visualisation of the outer periphery of the retina. This could potentially lead
      to novel clinical applications of these methods, with potential impact on therapy
      decisions. MATERIAL AND METHODS: Literature and database research on ultra-wide
      imaging for diabetic retinopathy and retinal vein occlusion. RESULTS: With ultra
      wide-angle angiography, it is possible to visualise up to 3.2-fold more retinal
      surface than conventional 7SF images (7SF: 7 standard field). Initial studies
      imply that diabetic changes can be found outside of the boundaries of the 7SF
      images. Patients with central vein occlusion have more extended and severe
      macular oedema and poorer visual acuity if ischemia of the periphery is more
      pronounced (measured by the ischemic index [ISI]). The amount of ischemia
      influences the size of the macular oedema, its resolution under therapy and the
      number of anti-VEGF injections needed to treat it. DISCUSSION: Ultra-wide-angle
      camera systems allow visualisation of the peripheral retina outside the
      boundaries of standard methods. Initial studies have detected potentially
      relevant changes in the outer periphery, which would have been missed by 7SF.
      Nevertheless, there have been no systematic studies on the relevance of these
      changes with regards to prognosis and therapeutic decisions.

PMID- 30216952
TI  - [Ultra-Wide Field Retinal Imaging and Angiography in the Differential Diagnosis
      and Therapeutic Decisions in Vascular Diseases of the Peripheral Retina].
AB  - Investigation of vascular diseases of the peripheral retina requires imaging
      procedures that allow a comprehensive view of the periphery, as well as
      reproducible pictures. In particular, ultra-wide field fluorescence angiography
      facilitates diagnosis, therapeutic decisions and follow-up examinations. While
      vasculopathies such as Coats disease and familiar exudative vitreoretinopathy are
      diagnosed within the first and second decade of life, patients' compliance during
      fundus imaging is typically reduced within this age range. Compared to the
      repeated imaging procedures for composite formation, ultra-wide field imaging has
      significantly reduced recording time. Nevertheless, current imaging systems are
      not able to map the entire retina in scaled proportions. Therefore, the imaging
      frame must be guided by patients' gaze onto the affected retinal area. Moreover,
      the medical photographer must be aware of the clinical setting and the region of
      interest. Hence, previous detailed funduscopy by trained ophthalmologists will
      remain indispensable.

PMID- 30216953
TI  - [Multimodal Imaging of the Choroidal Melanoma, with Differential Diagnosis,
      Therapy (Radiation Planning) and Follow-up].
AB  - Imaging of intraocular tumors is multimodal, multi-purpose, and in continuous
      development. Therefore, imaging is indispensable for the detection, diagnosis,
      therapy and monitoring of intraocular tumours. A broad spectrum of imaging
      procedures is available for diagnostic testing and follow-up. This includes
      colour image acquisition, infrared imaging, autofluorescence imaging,
      fluorescence and indocyanine green angiography, optical coherence tomography
      (OCT) and sonography (US). In this article, the various investigations and their
      benefits are described using individual examples for the differential diagnosis
      of choroidal melanoma and retinal vascular tumours located in the fundus
      periphery.

PMID- 30216954
TI  - Erratum to: The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE)
      Study for Patients on a Direct Oral Anticoagulant who Need an Elective Surgery or
      Procedure: Design and Rationale.

PMID- 30216955
TI  - Community-wide consequences of sexual dimorphism: evidence from nectar microbes
      in dioecious plants.
AB  - Intraspecific trait variation is receiving renewed interest as a factor affecting
      the structure of multi-species communities within and across trophic levels. One
      pervasive form of intraspecific trait variation is sexual dimorphism in animals
      and plants, which might exert large effects particularly on the communities of
      host-associated organisms, but the extent of these effects is not well
      understood. We investigated whether host-associated microbial communities
      developed differently in the floral nectar of female and male individuals of the
      dioecious shrubs, Eurya emarginata and E. japonica. We found that nectar
      colonizing microbes such as bacteria and fungi were more than twice as prevalent
      and, overall, more than 10 times as abundant in male flowers as in female
      flowers. Microbial species composition also differed between flower sexes. To
      examine potential mechanisms behind these differences, we manipulated the
      frequency of flower visitation by animals and the order of arrival of microbial
      species to nectar. Animal visitation frequency affected microbial communities
      more greatly in male flowers, while arrival order affected them more in female
      flowers. These sex-specific effects appeared attributable to differences in how
      animals and microbes altered the chemical characteristics of nectar that limited
      microbial growth. Taken together, our results provide evidence that sexual
      dimorphism can have large effects on the structure of host-associated
      communities.

PMID- 30216957
TI  - Correction.

PMID- 30216958
TI  - Correction.

PMID- 30216959
TI  - Molecular dissection of an inhibitor targeting the HIV integrase dependent
      preintegration complex nuclear import.
AB  - Human immunodeficiency virus (HIV) continues to be a major contributor to
      morbidity and mortality worldwide, particularly in developing nations where high
      cost and logistical issues severely limit the use of current HIV therapeutics.
      This, combined HIV's high propensity to develop resistance, means that new
      antiviral agents against novel targets are still urgently required. We previously
      identified novel anti-HIV agents directed against the nuclear import of the HIV
      integrase (IN) protein, which plays critical roles in the HIV lifecycle inside
      the cell nucleus, as well as in transporting the HIV preintegration complex (PIC)
      into the nucleus. Here we investigate the structure activity relationship of a
      series of these compounds for the first time, including a newly identified anti
      IN compound, budesonide, showing that the extent of binding to the IN core domain
      correlates directly with the ability of the compound to inhibit IN nuclear
      transport in a permeabilised cell system. Importantly, compounds that inhibited
      the nuclear transport of IN were found to significantly decrease HIV viral
      replication, even in a dividing cell system. Significantly, budesonide or its
      analogue flunisolide, were able to effect a significant reduction in the presence
      of specific nuclear forms of the HIV DNA (2-LTR circles), suggesting that the
      inhibitors work though blocking IN, and potentially PIC, nuclear import. The work
      presented here represents a platform for further development of these specific
      inhibitors of HIV replication with therapeutic and prophylactic potential.

PMID- 30216960
TI  - Evaluation of biochars in reducing the bioavailability of flubendiamide in
      water/sediment using passive sampling with polyoxymethylene.
AB  - An equilibrium passive sampler based on POM was first used to determine the Cfree
      of flubendiamide in water/sediment systems. The adsorption of flubendiamide by
      POM followed a first-order one-compartment uptake model and the POM-water
      partition coefficient was 1.90. The method was used to compare the efficiency of
      three biochars which were produced from crofton weed (BC-1, ~500 degrees C),
      macadamia (BC-2, 550-660 degrees C) and wheat straw (BC-3, 550 degrees C). The
      Freundlich fit the sorption isotherm data well and the adsorption capacity was BC
      1>BC-3>BC-2. The percent removal of the BC-1 was higher in acidic solutions. When
      different doses of BC-1 were added to two sediments, the Cfree of the
      flubendiamide was higher in the sediment with a low organic matter content (S-1).
      With an increase of BC-1, the Cfree was significantly reduced in S-1. A 30-day
      period of biochar-sediment contact time was sufficient for a reduction of freely
      dissolved flubendiamide in the case of the two sediments tested. In the
      combination of biochar addition (5%) and aging time (30days), the maximum
      reductions were 87% and 60% in S-1 and S-2. Therefore, the reduction of
      bioavailability of the flubendiamide and pollution repair can be achieved by this
      process.

PMID- 30216961
TI  - The interplay between reactive oxygen and nitrogen species contributes in the
      regulatory mechanism of the nitro-oxidative stress induced by cadmium in
      Arabidopsis.
AB  - Nitric oxide (NO) involved in various metabolic processes in plants. Although its
      significant influence has been established, the exact mechanisms of NO-derived
      products under metal-stress conditions are largely unknown. Here, we investigated
      the key components of reactive oxygen/nitrogen species (ROS/RNS) metabolisms
      under cadmium (Cd) stress using Arabidopsis as the model plant. Exposure to Cd
      disturbed redox homeostasis and increased lipid peroxidation, thus triggering
      oxidative stress. Complementarily, Cd caused differential changes in the selected
      amino acids: a promotion in partial amino acids might be a genotype-specific
      trait, while the phenylalanine ammonia-lyase activity increased in a dose
      dependent manner in shoots. Furthermore, NO production as well as S
      nitrosoglutathione (GSNO) reductase (GSNOR) activity were up-regulated by Cd with
      the simultaneous depletion of GSNO. Correspondingly, S-nitrosothiols were
      involved in generating peroxynitrite and tyrosine nitration of protein (NO2-Tyr),
      in accordance with the regulation of NO-mediated post-translational modifications
      in antioxidant systems, including the ascorbate-glutathione cycle, amino acids
      and phenolic compounds, thereby provoking nitrosative stress. Our data provide
      comprehensive evidences regarding the clear relationships between the metabolisms
      of ROS and RNS, supporting the indicator role of NO2-Tyr as a nitrosative stress
      in plants, and help to provide a better understanding of the ROS/RNS interaction
      under stress conditions.

PMID- 30216962
TI  - Pressure oscillation with destructive effect of flame propagation of a
      stoichiometric hydrogen-air mixture in a confined space.
AB  - In the present work, the formation mechanism of high-intensity combustion with
      high pressure oscillation and its destructive effects was studied by a newly
      designed constant volume combustion bomb equipped with a perforated plate. The
      stoichiometric H2-air mixture was selected as the test fuel because of its high
      flame propagation velocity with obvious shock wave, which easily leads to a
      strong pressure oscillation. Two kinds of high-intensity combustion phenomena,
      including the continuous acceleration of the flame front and end-gas auto
      ignition, were obtained. The results show that the ultrafast and intense
      combustion would lead to a high pressure oscillation, consequently caused damage
      to the experimental device, such as the optical glass and perforated plate. The
      perforated plate vibrated back and forth in situ forced by the combustion waves.
      The peak pressure was up to 10.3MPa and maximum amplitude of pressure oscillation
      was 4.2MPa when the optical glass was damaged. And according to FFT analysis, the
      frequency of in-cylinder pressure changed because of the combustion mode
      transition. The present work provides an alternative method to not only grasp the
      destructive mechanism of knocking combustion, but also understand the destructive
      effect of the combustion of the hydrogen-air mixture.

PMID- 30216963
TI  - Fast adsorption of heavy metal ions by waste cotton fabrics based double network
      hydrogel and influencing factors insight.
AB  - Massive consumption of cotton fabrics has brought up a serious problem concerning
      the waste cotton fabrics (WCFs) disposal. It is widely accepted that if WCFs can
      be reutilized, there will be great business potentials. Herein, we prepared a
      double network hydrogel based on WCFs and polyacrylamide (Cellulose/PAM DNHs) for
      heavy metal removal. The DNHs exhibit fast kinetics that sorption equilibrium is
      achieved in 5min because of the porous and sheet-like laminar structures they
      possess. The DNHs also illustrate excellent adsorption property and good
      reusability. The tandem two columns packed with Cellulose/PAM-3 can effectively
      process simulated and practical wastewater, and the adsorption discrepancy is
      negligible after three adsorption-desorption cycles. The treatment volumes of
      simulated wastewater are 172.5 BV (7935mL), 195 BV (8970mL), and 292.5 BV
      (13455mL) for Cd(II), Cu(II), and Pb(II), respectively. Furthermore, the
      treatment volumes of practical industrial wastewater reach 42 BV (1932mL) for
      Cd(II), 63 BV (2898mL) for Cu(II), and 87 BV (4002mL) for Zn(II), Pb(II) and Fe,
      respectively. This work provides a new avenue for the combination of WCFs reuse
      and heavy metal removal, which is of great importance to the construction of
      resource sustainability and environment-friendly society.

PMID- 30216964
TI  - Environmental impact and potential use of coal fly ash and sub-economical quarry
      fine aggregates in concrete.
AB  - The Israeli quarry industry produces 57 Mt of raw material and ~4-6Mt of
      associated sub-economical by-products annually. These sub-economical quarry fines
      are not used because production and transportation costs considerably exceed
      their retail value. Therefore these by-products, are stored in large piles of
      fine grain size particles, create environmental risks to their surrondings. This
      paper evaluates the possibility of mixing the sub-economical quarry by-products
      of two Israeli quarries with sub-economical Class F coal fly ash (<20wt.% CaO) to
      form an economical aggregate sand substitute to be used as a concrete filler
      product. To study the feasibility of the aggregate as partial substitute to sand
      in concrete several analyses, including leaching experiements (EN12457-2),
      analytical techinques (SEM-EDX, ICP-MS, ICP-AES, and XRD), as well as an analysis
      of the mechanical and chemical properties of the concrete aggregate (strength,
      workability, and penetration) were performed. Scrubbing quarry waste with coal
      fly ash was found to be very effective for reducing the leaching rate of
      potentially harmful trace elements. In addition, adding fly ash with quarry fines
      as partial substitute to sand enhanced the performance of the concrete mixture
      and the properties of the fresh and harden concrete.

PMID- 30216965
TI  - Transcriptional responses and mechanisms of copper nanoparticle toxicology on
      zebrafish embryos.
AB  - Copper nanoparticles (CuNPs) are used widely due to their attractive
      antimicrobial properties. However, their biosafety and kinetics on vertebrate
      embryogenesis are still limited. In this study, CuNPs were revealed to induce eye
      hypoplasia and almost no digestive gut in zebrafish embryos in a dose-dependent
      manner. Then, transcriptional responses of zebrafish embryos to CuNPs were
      investigated, and it was revealed that the genes related to wound healing and
      stimulus responses were up-regulated, but the genes associated with
      phototransduction and metabolisms were down-regulated. Differentially expressed
      genes (DEGs) in CuNPs-exposed and Cu2+-exposed embryos were compared further.
      Increased VEGF signaling and expression of fli1 were observed in CuNPs rather
      than Cu2+ treated embryos, but increased reactive oxygen species (ROS) and the
      resulting enhanced hemoglobin were observed in both CuNPs and Cu2+ treated
      embryos. This study for the first time revealed that CuNPs and Cu2+ both down
      regulated the genes related to phototransduction and metabolisms, but up
      regulated the genes associated with hemoglobin. Additionally, compared with Cu2+,
      CuNPs might be more effective in elevating blood vessels in embryos. Our results
      suggest that the biological effects of CuNPs are organogenesis-specific during
      fish embryogenesis, and both particles and ions might mediate their biological
      effects on embryogenesis.

PMID- 30216966
TI  - Adsorptive removal of aromatic hydrocarbons from water over metal azolate
      framework-6-derived carbons.
AB  - Metal azolate framework-6 (MAF-6) was pyrolyzed at 1000 degrees C to yield MOF
      derived carbons (MCs). The obtained MCs were used to eliminate aromatic
      hydrocarbons, including polyaromatic hydrocarbons (PAHs; e.g., naphthalene (NAP),
      anthracene (ATC), and pyrene (PRN)) and benzene (BZ) from water via adsorption.
      The adsorption results over the MCs were compared with that of pristine MAF-6 and
      commercial activated carbon (AC). MC obtained after 24h (MC-24) exhibited a
      remarkable adsorption efficiency compared to that of the other MCs (obtained
      after different durations), MAF-6, and AC. For example, MC-24 led to adsorptions
      of NAP around 17 and 2.5 times those of pristine MAF-6 and AC, respectively. Or,
      the maximum adsorption capacities (Q0) of MAF-6, AC and MC-24 for NAP were 14,
      104 and 237mg/g, respectively. Moreover, Q0 values of MC-24 for ATC and PRN were
      also very high of 284 and 307mg/g, respectively. Based on the properties of PAHs
      and the hydrophobicity of MC-24, hydrophobic interaction was suggested as the
      main mechanism for the adsorption of PAHs and BZ. In addition, MC-24 can be
      recycled by washing with acetone with little loss in performance. Therefore, MC
      24 is recommended as a competitive adsorbent for aromatic hydrocarbon removal
      from water.

PMID- 30216967
TI  - In situ growth of 0D silica nanospheres on 2D molybdenum disulfide nanosheets:
      Towards reducing fire hazards of epoxy resin.
AB  - This report described a facile process for the preparation of 2D/0D MoS2-SiO2
      hybrids using a simple in situ growth method, with the purpose of promoting the
      dispersion of MoS2 in polymer matrices and improving the properties of polymer
      materials. FTIR, XPS, TGA and TEM measurements were performed to characterize the
      structure and morphology of the synthesized hybrids which were then introduced
      into epoxy to reduce flammability. The hybrids dispersed well in the epoxy
      matrix. No obvious agglomerations were observed. In comparison with those of neat
      epoxy, the incorporation of a low loading of MoS2-SiO2 hybrids resulted in
      significant decrements in heat release rate, total heat release and volume of
      toxic effluents released during combustion, which indicated that the fire hazards
      of epoxy composites were strongly reduced. The good dispersion, labyrinth barrier
      effect and the catalytic effect of MoS2-SiO2 hybrids on char formation may
      contribute to the observed decrease in the flammability of epoxy resin.

PMID- 30216968
TI  - Amino-functionalized hierarchical porous SiO2-AlOOH composite nanosheets with
      enhanced adsorption performance.
AB  - Hierarchical porous SiO2-AlOOH composite nanosheets (HPSA) with a three
      dimensional (3D) structure were prepared from two-dimensional (2D) layered
      mineral kaolinite (A12Si2O5(OH)4) via a template-free structural reorganization
      method. The obtained material was subjected to homogeneous and effective amino
      functionalization by grafting it with (3-aminopropyl) triethoxysilane. Owing to
      the enhanced 3D hierarchical meso-macroporous structure containing highly
      dispersed protonated amino groups (NH3+), the as-prepared amino-functionalized
      HPSA (NH2-HPSA) showed unique adsorption performance towards the congo red
      anionic dye. It provides feasibilities to fabricate other functional hierarchical
      porous materials from clay minerals, which can offer potential applications in
      adsorption, separation, catalysis and other environmental remediation fields.

PMID- 30216969
TI  - Impacts of moisture content during ozonation of soils containing residual
      petroleum.
AB  - We tested the effect of soil moisture content on the efficiency of gas-phase
      ozonation for two types of soils containing residual petroleum. For the first
      soil (BM2), having a total petroleum hydrocarbons (TPH) concentration of
      18,000mg/kg soil, a moisture content of 5% benefited oxidation, giving the
      highest efficiency of ozonation for TPH removal and for producing soluble and
      biodegradable products. In contrast, higher moisture content hindered O3 from
      oxidizing reactive materials in the second soil (BM3), which had a higher TPH
      concentration, 33,000mg/kg soil. This trend was documented by less TPH removal,
      less generation of soluble and biodegradable organic products, and a carbon
      balance that showed retarded carbon oxidation. An unexpected phenomenon was
      smoldering during ozonation of air-dried (<1% moisture) BM3, which did not occur
      with the same moisture conditions for BM2. BM3 smoldered was due to its higher
      TPH content, low heat buffering, and more release of volatiles with low self
      ignition points. Smoldering did not occur for >= 5% water content, as it
      suppressed the temperature increase needed to volatilize the organics that
      initiated smoldering. The findings underscore the importance of controlling water
      content during ozonation to optimize the effectiveness of ozonation and prevent
      smoldering.

PMID- 30216970
TI  - Treatment of textile dyeing industry effluent using hydrodynamic cavitation in
      combination with advanced oxidation reagents.
AB  - Treatment of textile dyeing industry (TDI) effluent was investigated using
      hydrodynamic cavitation (HC) and in combination with advanced oxidation reagents
      such as air, oxygen, ozone and Fenton's reagent. Slit venturi was used as the
      cavitating device in HC reactor. The effects of process parameters such as inlet
      pressure, cavitation number, effluent concentration, ozone and oxygen flow rate,
      loading of H2O2 and Fenton's reagent on the extent of reduction of TOC, COD and
      color were studied. Efficiency of the hybrid treatment processes were evaluated
      on the basis of their synergetic coefficient. It was observed that almost 17%
      TOC, 12% COD, and 25% color removal was obtained using HC alone at inlet pressure
      of 5bar and pH of 6.8. The rate of reduction of TOC and COD decreased with
      dilution of the samples. HC in combination with Fenton's reagent (FeSO4.7H2O:H2O2
      as 1:5) was most effective with reduction of 48%TOC and 38% COD in 15min and
      120min respectively with almost complete decolorization (98%) of the TDI
      effluent. Whereas HC in combination with oxygen (2L/min) and ozone (3g/h)
      produced reduction of 48% TOC, 33% COD, 62% decolorization and 48% TOC, 23% COD,
      88%, decolorization of TDI effluent respectively.

PMID- 30216971
TI  - Degradation of polychlorinated dibenzo-p-dioxins and dibenzofurans in real-field
      soil by an integrated visible-light photocatalysis and solvent migration system
      with p-n heterojunction BiVO4/Bi2O3.
AB  - Degradation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in
      real-field soil was conducted using an integrated photocatalysis-solvent
      migration system of BiVO4/Bi2O3 and n-hexane. The photocatalyst BiVO4/Bi2O3 was
      synthesized, and its performance was found to be affected by the BiVO4 content,
      with 20wt% BiVO4 showing the best performance owing to its p-n heterojunction
      being well formed. Migration was affected by the amount of n-hexane, with 15% n
      hexane giving the most effective transportation of PCDD/Fs. 37.2% of 17 PCDD/Fs
      was removed in 60h by the integrated photocatalysis-solvent migration system,
      although the reaction zone covered 8.5% of the volume of the soil. The result
      showed that migration via n-hexane fulfilled the aim of carrying contaminants
      from inside of the soil to the surface. Electron-scavenging experiments with
      BiVO4/Bi2O3 showed an 18.4% of performance in removal compared to no-scavenging
      condition, which showed that the main reactions driving BiVO4/Bi2O3 visible-light
      photocatalysis for aryl-chloride were found to be reduction-based. Owing to the
      hindering effect of Cl atoms, degradation by hydroxyl radical could proceed after
      initial dechlorination. This study establishes the applicability of integrated
      photocatalysis-solvent migration systems in real-field settings, and is the first
      report of a visible-light photocatalyst, BiVO4/Bi2O3, for the degradation of
      PCDD/Fs in soil.

PMID- 30216972
TI  - Cloning and expression of the carbaryl hydrolase gene mcbA and the identification
      of a key amino acid necessary for carbaryl hydrolysis.
AB  - Carbamate hydrolase is the initial and key enzyme for degradation of carbamate
      pesticides. In the present study, we report the isolation of a carbaryl-degrading
      strain Pseudomonas sp. XWY-1, the cloning of its carbaryl hydrolase gene (mcbA)
      and the characterization of McbA. Strain XWY-1 was able to utilize carbaryl as a
      sole carbon source and degrade it using 1-naphthol as an intermediate. Transposon
      mutagenesis identified a mutant of XWY-1M that was unable to hydrolyze carbaryl.
      The transposon-disrupted gene mcbA was cloned by self-formed adaptor PCR, then
      expressed in Escherichia coli BL21(DE3) and purified. McbA was able to hydrolyze
      carbamate pesticides including carbaryl, isoprocarb, fenobucarb, carbofuran
      efficiently, while it hydrolyzed aldicarb, and propoxur poorly. The optimal pH of
      McbA was 7.0 and the optimal temperature was 40 degrees C. The apparent Km and
      kcat values of McbA for carbaryl were 77.67+/-12.31MUM and 2.12+/-0.10s-1,
      respectively. Three amino acid residues (His467, His477 and His504) in the
      predicted polymerase/histidinol phosphatase-like domain were shown to be closely
      related to the activity of McbA, with His504 being the most important, as a
      replacement of His504 led to the complete loss of activity. This is the first
      study to identify key amino acids in McbA.

PMID- 30216973
TI  - Recoverable amphiphilic polyoxoniobates catalyzing oxidative and hydrolytic
      decontamination of chemical warfare agent simulants in emulsion.
AB  - Amphiphilic polyoxoniobates (PONbs), [CnH2n+1N(CH3)3]7HNb6O19 (for 1, n=14; for
      2, n=16; and for 3, n=18), were successfully prepared by the electrostatic
      interaction of hexaniobate anions with quaternary ammoniums containing long alkyl
      chain, and thoroughly characterized by using various techniques including Fourier
      transform infrared (FT-IR), 1H nuclear magnetic resonance (1H NMR), 13C nuclear
      magnetic resonance (13C NMR), thermogravimetric analysis (TGA), and elemental
      analysis. All three PONbs were used in the emulsion systems to catalytically
      decontaminate chemical warfare agent simulants and the influences of quaternary
      ammonium cations, polyanions, and amount of catalyst on the catalytic efficiency
      have been evaluated. Under optimal conditions, catalyst 3 in emulsion can
      completely convert both a the nerve agent simulant, diethyl cyanophosphonate
      (DECP), in 2h by hydrolysis and a sulfur mustard simulant, 2-chloroethyl ethyl
      sulfide (CEES), in 20min by oxidation using nearly stoichiometric 3% aqueous
      H2O2. Moreover, the amphiphilic catalyst 3 can be simply separated and readily
      reused for five recycles without obvious losing its activity. To the best of our
      knowledge, this study represents the first example where the emulsions of PONbs
      are used in the catalysis.

PMID- 30216974
TI  - Therapeutic Potential of Brazilian Cerrado Campomanesia Species on Metabolic
      Dysfunctions.
AB  - Obesity, in conjunction with other metabolic disorders such as insulin resistance
      and dyslipidemia, is a feature of metabolic syndrome which is characterized by a
      pro-inflammatory state and increased oxidative stress. Therefore, antioxidant
      foods are proposed to prevent and treat these disorders. Medicinal plants are one
      of the main strategies in this regard. Guavira, a Brazilian Cerrado plant,
      contains different bioactive compounds with a high antioxidant capacity and
      without clinical or reproductive toxicity effects. Though there are different
      varieties of guavira, the principal Brazilian Cerrado guaviras demonstrated
      hypoglycemic, anti-inflammatory, and hypocholesterolemic actions. There is also a
      potential antiplatelet agent in C. xanthocarpa, while C. adamantium displayed
      hypocholesterolemic actions in animal models and human clinical trials. On the
      other hand, even with a lack of studies related to C. pubescens, it demonstrated
      anti-inflammatory effects and an antioxidant capacity in in vitro studies.
      Despite the fact that most of the studies were not performed to evaluate
      pathological conditions specific to obese animal models or obese subjects,
      guavira demonstrated effects in metabolic disorders that are commonly related to
      the obesity context, such as cardiovascular disturbances and hyperglycemia
      status. This suggests that guavira is a potential therapeutic approach to obesity
      induced metabolic syndrome.

PMID- 30216975
TI  - Selection and Identification of Novel Aptamers Specific for Clenbuterol Based on
      ssDNA Library Immobilized SELEX and Gold Nanoparticles Biosensor.
AB  - We describe a multiple combined strategy to discover novel aptamers specific for
      clenbuterol (CBL). An immobilized ssDNA library was used for the selection of
      specific aptamers using the systematic evolution of ligands by exponential
      enrichment (SELEX). Progress was monitored using real-time quantitative PCR (Q
      PCR), and the enriched library was sequenced by high-throughput sequencing.
      Candidate aptamers were picked and preliminarily identified using a gold
      nanoparticles (AuNPs) biosensor. Bioactive aptamers were characterized for
      affinity, circular dichroism (CD), specificity and sensitivity. The Q-PCR
      amplification curve increased and the retention rate was about 1% at the eighth
      round. Use of the AuNPs biosensor and CD analyses determined that six aptamers
      had binding activity. Affinity analysis showed that aptamer 47 had the highest
      affinity (Kd = 42.17 +/- 8.98 nM) with no cross reactivity to CBL analogs.
      Indirect competitive enzyme linked aptamer assay (IC-ELAA) based on a 5'-biotin
      aptamer 47 indicated the limit of detection (LOD) was 0.18 +/- 0.02 ng/L (n = 3),
      and it was used to detect pork samples with a mean recovery of 83.33-97.03%. This
      is the first report of a universal strategy including library fixation, Q-PCR
      monitoring, high-throughput sequencing, and AuNPs biosensor identification to
      select aptamers specific for small molecules.

PMID- 30216976
TI  - Growth and Development of Children with Microcephaly Associated with Congenital
      Zika Virus Syndrome in Brazil.
AB  - The outbreak of Zika virus in Latin America in the period 2015-2016 has caused a
      sudden increase in the number of severe manifestations and reports of congenital
      changes in newborns in Brazil. This is the first study that evaluated and
      compared the growth and cognitive and motor development of children with
      microcephaly due to Congenital Zika Virus Syndrome (CZS) in relation to typical
      children. It was an observational, analytical, cross-sectional study with 8
      children with CZS and 16 typical children, with a mean age of 20.5 months (+/
      2.1), in a region of northeastern Brazil. Considering the mean, children with CZS
      presented extremely low performance in the motor domain and in the cognitive
      development domain, whereas typical children presented average performance in the
      cognitive and motor development domains. Children with CZS presented a mean
      growth rate (head circumference and weight) lower than typical children.
      Therefore, children with CZS are at risk for growth retardation and development
      compared to typical children.

PMID- 30216978
TI  - The Response of IL-17-Producing B Cells to ArtinM Is Independent of Its
      Interaction with TLR2 and CD14.
AB  - ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus, activates
      antigen-presenting cells by recognizing Toll-like receptor (TLR)2 and cluster of
      differentiation (CD)14 N-glycans, induces cytokine production, and promotes type
      1 T helper (Th1) immunity, a process that plays an assisting role in the combat
      against fungal infections. We recently demonstrated that ArtinM stimulates CD4+ T
      cells to produce interleukin (IL)-17 through direct interaction with CD3. Here,
      we further investigated the effects of ArtinM on the production of IL-17 by B
      cell activation. We showed that ArtinM activates murine B cells, increasing IL-17
      and IL-12p40 production. The direct effect of ArtinM was sufficient to induce IL
      17 production in B cells, and we did not find differences in the levels of IL-17
      between the B cells purified from the wild-type (WT) and knockout (KO) mice for
      TLR2 or CD14 in the presence of ArtinM. Thus, the effects of ArtinM on splenic B
      cells through carbohydrate recognition may contribute to Th17 immunity; however,
      the mechanism involved is not associated with the interaction of ArtinM with TLR2
      and CD14. The current work represents a pioneering effort in the understanding of
      the induction of IL-17 by lectins in B cells.

PMID- 30216979
TI  - Theoretical and Experimental Study on the Effective Piezoelectric Properties of 1
      3 Type Cement-Based Piezoelectric Composites.
AB  - The double asymptotic homogenization method originated for analyzing physical
      systems containing two or more length scales was adopted to predict the
      characteristic of 1-3 type cement-based piezoelectric composites for the first
      time. The piezoelectric properties of 1-3 type cement-based piezoelectric
      composites were measured and comparisons between the experimental data and
      predicted values validate the effectiveness of the present analytical model.
      Moreover, numerical discussions and experiments show that one should choose
      proper volume fraction of constituents to achieve the best performance of the 1-3
      type cement-based piezoelectric composites.

PMID- 30216980
TI  - Enhancing High-Frequency Dielectric Properties of Beta-SiC Filled Nanocomposites
      from Synergy between Percolation and Polarization.
AB  - Promising comprehensive properties, including high permittivity, low dielectric
      loss, high breakdown strength, low electrical conductivity, and high thermal
      conductivity, are very hard to simultaneously obtain in high-frequency applicable
      polymer nanocomposite dielectrics. Instead of traditional electric percolation,
      in this work, a novel route based on a synergy between electric percolation and
      induced polarization has been raised to prepare 0-3 type nanocomposites with an
      enhanced high permittivity (high-k) property and low loss at high frequency. This
      work aimed at optimizing that synergy to achieve the favorable properties
      mentioned above in composite dielectrics used at high frequencies such as 1 MHz
      and 1 GHz. Conductive beta-SiC nanoparticles with a particle size of ~30 nm were
      employed as filler and both insulating poly(vinyl alcohol) and polyvinyl chloride
      were employed as polymer matrices to construct two composite systems. Utilizing
      polyvinyl chloride rather than poly(vinyl alcohol) realizes higher comprehensive
      electrical properties in composites, ascribed to optimization of that synergy.
      The optimization was achieved based on a combination of mild induced polarization
      and polarization-assisted electric percolation. Therefore, this work might open
      the way for large-scale production of high-frequency applicable composite
      dielectrics with competitive comprehensive electrical properties.

PMID- 30216977
TI  - The Anti-Inflammatory Effects of Vitamin D in Tumorigenesis.
AB  - In conjunction with the classical functions of regulating intestinal, bone, and
      kidney calcium and phosphorus absorption, as well as bone mineralization of
      vitamin D, the population-based association between low vitamin D status and
      increased cancer risk is now generally accepted. Inflammation is causally related
      to oncogenesis. It is widely thought that vitamin D plays an important role in
      the modulation of the inflammation system by regulating the production of
      inflammatory cytokines and immune cells, which are crucial for the pathogenesis
      of many immune-related diseases. Mechanistic studies have shown that vitamin D
      influences inflammatory processes involved in cancer progression, including
      cytokines, prostaglandins, MAP kinase phosphatase 5 (MKP5), the nuclear factor
      kappa B (NF-kappaB) pathway, and immune cells. Multiple studies have shown that
      vitamin D has the potential to inhibit tumor development by interfering with the
      inflammation system. The present review summarizes recent studies of the
      mechanisms of vitamin D on regulating the inflammation system, which contributes
      to its potential for cancer prevention and therapy. This review helps answer
      whether inflammation mediates a causal relationship between vitamin D and
      tumorigenesis.

PMID- 30216982
TI  - Influence of Multi-Holes on Fatigue Behaviors of Cast Magnesium Alloys Based on
      In-Situ Scanning Electron Microscope Technology.
AB  - The low cycle fatigue tests on the crack initiation and propagation of cast
      magnesium alloys with two small holes were carried out by using in-situ scanning
      electron microscope (SEM) observation technology. The fatigue crack propagation
      behaviors and fatigue life, which are affected by two small artificial through
      holes, including the distances between two holes and their locations, were
      discussed in detail based on the experimental results and the finite element
      analysis (FEA). The results indicated that the fatigue multi-cracks occurred
      chiefly at the edges of two holes and the main crack propagation was along the
      weak dendrite boundary with the plastic deformation vestiges on the surface of
      alpha-Mg phase of cast AM50 and AM60B alloys. The fatigue cracking
      characteristics of cast AZ91 alloy depended mainly on the brittle properties of
      beta-Mg17Al12 phase, in which the multi-cracks occurred still at the edges of two
      holes and boundaries of beta-Mg17Al12 phase. The fatigue crack initiation
      position of cast magnesium alloys depends strongly on the radius of curvature of
      through hole or stress concentration factor at the closed edges of two through
      holes. In addition, the fatigue multi-cracks were amalgamated for the samples
      with titled 45 degrees  of two small holes of cast Mg-Al alloys when the hole
      distance is less than 4D (D is the diameter of the small hole).

PMID- 30216981
TI  - The Flavonoid Kaempferol Ameliorates Streptozotocin-Induced Diabetes by
      Suppressing Hepatic Glucose Production.
AB  - In diabetes mellitus, the excessive rate of glucose production from the liver is
      considered a primary contributor for the development of hyperglycemia, in
      particular, fasting hyperglycemia. In this study, we investigated whether
      kaempferol, a flavonol present in several medicinal herbs and foods, can be used
      to ameliorate diabetes in an animal model of insulin deficiency and further
      explored the mechanism underlying the anti-diabetic effect of this flavonol. We
      demonstrate that oral administration of kaempferol (50 mg/kg/day) to
      streptozotocin-induced diabetic mice significantly improved hyperglycemia and
      reduced the incidence of overt diabetes from 100% to 77.8%. This outcome was
      accompanied by a reduction in hepatic glucose production and an increase in
      glucose oxidation in the muscle of the diabetic mice, whereas body weight,
      calorie intake, body composition, and plasma insulin and glucagon levels were not
      altered. Consistently, treatment with kaempferol restored hexokinase activity in
      the liver and skeletal muscle of diabetic mice while suppressed hepatic pyruvate
      carboxylase activity and gluconeogenesis. These results suggest that kaempferol
      may exert antidiabetic action via promoting glucose metabolism in skeletal muscle
      and inhibiting gluconeogenesis in the liver.

PMID- 30216983
TI  - Oxidative Damage and Nrf2 Translocation Induced by Toxicities of Deoxynivalenol
      on the Placental and Embryo on Gestation Day 12.5 d and 18.5 d.
AB  - Deoxynivalenol (DON) is a kind of natural pollutant belonging to the
      trichothecenes family. The aim of this study is to use diverse assays to evaluate
      oxidative damage as well as translocation of nuclear factor erythroid 2-related
      factor 2 (Nrf2), and to investigate their mechanisms in DON-induced toxicities on
      a placenta and embryo. Pregnant C57BL/6 mice were randomly assigned to three
      groups with different doses of DON: 0, 1.0, 2.5 mg/(kg.day). In gestation day
      (GD) 12.5 d and 18.5 d, DON induced an elevated resorption rate of the embryos as
      well as structural and functional damage of the placenta. In the placenta,
      altered levels of the antioxidant enzymes malondialdehyde, superoxide dismutase
      and glutathione indicated remarkable oxidative stress. Furthermore, an elevated
      level of heme oxygenase-1 (HO-1) and the translocation of Nrf2 from nucleus to
      cytoplasm indicated Nrf2/HO-1 pathway activation in DON-L group (1.0
      mg/(kg.day)). It is noteworthy that the results in this experiment in GD 12.5 d
      were similar to those in GD 18.5 d. In conclusion, DON-induced placental
      oxidative damage and Nrf2 translocation were similar in GD 12.5 d and GD 18.5 d.
      Oxidative stress is one of the most important molecular mechanisms for
      embryotoxicity induced by DON, and Nrf2 translocation may play a substantial role
      against it.

PMID- 30216984
TI  - Effect of Piperine on Skin Permeation of Curcumin from a Bacterially Derived
      Cellulose-Composite Double-Layer Membrane for Transdermal Curcumin Delivery.
AB  - Curcumin is a naturally occurring substance with various pharmacological
      activities. It has not been developed as a drug because of its low
      bioavailability due to its low solubility and absorption. Piperine is a natural
      enhancer that is popularly used to increase the absorption of curcumin in oral
      applications; however, it has not been applied for transdermal curcumin delivery.
      This study aims to develop a transdermal curcumin delivery system using piperine
      as a skin permeation enhancer in the form of composite double-layer membrane; the
      upper layer consisted of curcumin and the lower layer consisted of piperine. The
      amount of curcumin was fixed, but the amount of piperine varied at three levels
      from 1.96% to 7.41%. The composite membrane had moderate mechanical strength (15
      22 MPa) with a good swelling degree (~435%). From an in vitro skin permeation
      study, piperine had the effect to increase the permeation of curcumin. The
      permeation rate was related to the amount of piperine. The composite membrane
      containing piperine at 7.41% could increase the permeation rate of curcumin by
      about 1.89 times compared with non-piperine contained membrane. Bacterially
      derived cellulose containing curcumin and piperine may have the potential for
      transdermal curcumin delivery in order to improve curcumin's bioavailability.

PMID- 30216985
TI  - Correction: Brazda, V. and Coufal, J. Recognition of Local DNA Structures by p53
      Protein. Int. J. Mol. Sci. 2017, 18, 375.
AB  - The authors wish to make the following corrections to their paper [1] [...].

PMID- 30216986
TI  - Optimization of Antioxidant and Skin-Whitening Compounds Extraction Condition
      from Tenebrio molitor Larvae (Mealworm).
AB  - Skin-whitening ingredients are a very important part of the development of
      functional cosmetics and a wide variety of raw materials are used. Tyrosinase is
      a key enzyme in the animal melanogenic pathway that is the rate-limiting step for
      the production of melanin. Several synthetic and naturally occurring tyrosinase
      inhibitors have been studied for skin-whitening. The development of natural
      agents is becoming more important due to the disadvantages of synthetics such as
      high cytotoxicity, insufficient penetration power, and low activity. The purpose
      of this study was to evaluate the total phenol content (TPC), antioxidant, and
      tyrosinase inhibition activity of mealworm (Tenebrio molitor larvae) extract, and
      the subsequent optimization of the extraction condition using statistically-based
      optimization. The major extraction variables extraction temperature, time, and
      ethanol concentration were optimized using response surface methodology (RSM).
      The results showed that optimum extraction temperature of 88.1  degrees C,
      extraction time of 43.7 min, and ethanol concentration of 72.0 v/v%, provided the
      predicted maximum levels of total phenolic compounds (TPC) of 5.41 mg GAE/g dry
      weight (DW) and tyrosinase inhibition activity (TIA) of 82.4%. From the
      validation experiment, 5.61 +/- 0.2 mg GAE/g dry weight (DW), tyrosinase
      inhibition of 79.6 +/- 3.3%, and radical scavenging activity of 91.8 +/- 5.1
      MUg/mL were found and showed to be very similar to the predicted values. These
      results suggest that mealworm has great potential as a source of bioactive
      compounds which could be used as cosmetics, food, and pharmaceutical agents.

PMID- 30216987
TI  - The Amino Acid Composition of Quadruplex Binding Proteins Reveals a Shared Motif
      and Predicts New Potential Quadruplex Interactors.
AB  - The importance of local DNA structures in the regulation of basic cellular
      processes is an emerging field of research. Amongst local non-B DNA structures, G
      quadruplexes are perhaps the most well-characterized to date, and their presence
      has been demonstrated in many genomes, including that of humans. G-quadruplexes
      are selectively bound by many regulatory proteins. In this paper, we have
      analyzed the amino acid composition of all seventy-seven described G-quadruplex
      binding proteins of Homo sapiens. Our comparison with amino acid frequencies in
      all human proteins and specific protein subsets (e.g., all nucleic acid binding)
      revealed unique features of quadruplex binding proteins, with prominent
      enrichment for glycine (G) and arginine (R). Cluster analysis with bootstrap
      resampling shows similarities and differences in amino acid composition of
      particular quadruplex binding proteins. Interestingly, we found that all
      characterized G-quadruplex binding proteins share a 20 amino acid long
      motif/domain (RGRGR GRGGG SGGSG GRGRG) which is similar to the previously
      described RG-rich domain (RRGDG RRRGG GGRGQ GGRGR GGGFKG) of the FRM1 G
      quadruplex binding protein. Based on this protein fingerprint, we have predicted
      a new set of potential G-quadruplex binding proteins sharing this interesting
      domain rich in glycine and arginine residues.

PMID- 30216988
TI  - External Quality Assessment (EQA) for Molecular Diagnostics of Zika Virus:
      Experiences from an International EQA Programme, 2016-2018.
AB  - Quality Control for Molecular Diagnostics (QCMD), an international provider for
      External Quality Assessment (EQA) programmes, has introduced a programme for
      molecular diagnostics of Zika virus (ZIKV) in 2016, which has been continuously
      offered to interested laboratories since that time. The EQA schemes provided from
      2016 to 2018 revealed that 86.7% (92/106), 82.4% (89/108), and 88.2% (90/102) of
      the participating laboratories reported correct results for all samples,
      respectively in 2016, 2017, and 2018. The review of results indicated a need for
      improvement concerning analytical sensitivity and specificity of the test
      methods. Comparison with the outcomes of other EQA initiatives briefly summarized
      here show that continuous quality assurance is important to improve laboratory
      performance and to increase preparedness with reliable diagnostic assays for
      effective patient management, infection and outbreak control.

PMID- 30216990
TI  - Measurement and Analysis of Thermal Conductivity of Ti3C2Tx MXene Films.
AB  - A new class of 2D materials named "MXene" has recently received significant
      research interest as they have demonstrated great potential for the applications
      in batteries, supercapacitors, and electronic devices. However, the research on
      their thermal properties is still very limited. In this work, Ti3C2Tx films were
      prepared by the vacuum-assisted filtration of delaminated nano-flake Ti3C2Tx
      MXenes. The thermal and electrical conductivity of the Ti3C2Tx films were
      measured by the state-of-the-art T-type method. The results showed that the
      effective thermal conductivity of the films increased from 1.26 W.m-1.K-1 at 80 K
      to 2.84 W.m-1.K-1 at 290 K, while the electrical conductivity remained at 12,800
      Omega-1.m-1 for the same temperature range. Thermal resistance model was applied
      to evaluate the inherent thermal conductivity of the Ti3C2Tx flakes, which was
      estimated to be in the range of tens to hundreds W.m-1.K-1.

PMID- 30216989
TI  - Sirtuins and Immuno-Metabolism of Sepsis.
AB  - Sepsis and septic shock are the leading causes of death in non-coronary intensive
      care units worldwide. During sepsis-associated immune dysfunction, the
      early/hyper-inflammatory phase transitions to a late/hypo-inflammatory phase as
      sepsis progresses. The majority of sepsis-related deaths occur during the hypo
      inflammatory phase. There are no phase-specific therapies currently available for
      clinical use in sepsis. Metabolic rewiring directs the transition from hyper
      inflammatory to hypo-inflammatory immune responses to protect homeostasis during
      sepsis inflammation, but the mechanisms underlying this immuno-metabolic network
      are unclear. Here, we review the roles of NAD+ sensing Sirtuin (SIRT) family
      members in controlling immunometabolic rewiring during the acute systemic
      inflammatory response associated with sepsis. We discuss individual contributions
      among family members SIRT 1, 2, 3, 4 and 6 in regulating the metabolic switch
      between carbohydrate-fueled hyper-inflammation to lipid-fueled hypo-inflammation.
      We further highlight the role of SIRT1 and SIRT2 as potential "druggable" targets
      for promoting immunometabolic homeostasis and increasing sepsis survival.

PMID- 30216992
TI  - Anti-Inflammatory and Skin-Moisturizing Effects of a Flavonoid Glycoside
      Extracted from the Aquatic Plant Nymphoides indica in Human Keratinocytes.
AB  - Nymphoides indica, an aquatic plant, is used as folk medicine in some countries.
      Our previous study demonstrated that the methanol extract of N. indica inhibited
      the activity of tyrosinases, tyrosine related protein (TRP)1 and TRP2, and
      microphthalmia-associated transcription factor, as well as the activity of
      protein kinase A, by effectively inhibiting cyclic adenosine monophosphate.
      Although the biological activities of N. indica extract have been reported, there
      are no reports on the skin bioactivity of the main compound(s) on human
      keratinocytes. This study investigated the anti-inflammatory and moisturizing
      effects of quercetin 3,7-dimethyl ether 4'-glucoside (QDG) isolated from N.
      indica. In brief, ultraviolet B irradiated keratinocytes were pretreated with
      different concentrations of QDG, and the effects of QDG on various inflammatory
      markers were determined. QDG significantly inhibited inflammation-related
      cytokines and chemokines and enhanced the activation of skin barrier factors.
      Additionally, QDG also attenuated phosphorylation inhibition of the upstream
      cytokines and nuclear factor-kappaB expression. These results suggest that QDG
      isolated from N. indica may serve as a potential source of bioactive substances
      for chronic inflammatory skin diseases.

PMID- 30216991
TI  - Synthetic and Marine-Derived Porous Scaffolds for Bone Tissue Engineering.
AB  - Bone is a vascularized and connective tissue. The cortical bone is the main part
      responsible for the support and protection of the remaining systems and organs of
      the body. The trabecular spongy bone serves as the storage of ions and bone
      marrow. As a dynamic tissue, bone is in a constant remodelling process to adapt
      to the mechanical demands and to repair small lesions that may occur.
      Nevertheless, due to the increased incidence of bone disorders, the need for bone
      grafts has been growing over the past decades and the development of an ideal
      bone graft with optimal properties remains a clinical challenge. This review
      addresses the bone properties (morphology, composition, and their repair and
      regeneration capacity) and puts the focus on the potential strategies for
      developing bone repair and regeneration materials. It describes the requirements
      for designing a suitable scaffold material, types of materials (polymers,
      ceramics, and composites), and techniques to obtain the porous structures
      (additive manufacturing techniques like robocasting or derived from marine
      skeletons) for bone tissue engineering applications. Overall, the main objective
      of this review is to gather the knowledge on the materials and methods used for
      the production of scaffolds for bone tissue engineering and to highlight the
      potential of natural porous structures such as marine skeletons as promising
      alternative bone graft substitute materials without any further mineralogical
      changes, or after partial or total transformation into calcium phosphate.

PMID- 30216993
TI  - Influence of Modified Fucoidan and Related Sulfated Oligosaccharides on
      Hematopoiesis in Cyclophosphamide-Induced Mice.
AB  - Immunosuppression derived after cytostatics application in cancer chemotherapy is
      considered as an adverse side effect that leads to deterioration of quality of
      life and risk of infectious diseases. A linear sulfated (1->3)-alpha-l-fucan M
      Fuc prepared by chemical modification of a fucoidan isolated from the brown
      seaweed Chordaria flagelliformis, along with two structurally related synthetic
      sulfated oligosaccharides, were studied as stimulators of hematopoiesis on a
      model of cyclophosphamide immunosuppression in mice. Recombinant granulocyte
      colony-stimulating factor (r G-CSF), which is currently applied in medicine to
      treat low blood neutrophils, was used as a reference. Polysaccharide M-Fuc and
      sulfated difucoside DS did not demonstrate significant effect, while sulfated
      octasaccharide OS showed higher activity than r G-CSF, causing pronounced
      neutropoiesis stimulation. In addition, production of erythrocytes and platelets
      was enhanced after the octasaccharide administration. The assessment of
      populations of cells in blood and bone marrow of mice revealed the difference in
      mechanisms of action of OS and r G-CSF.

PMID- 30216994
TI  - Pipeline Inspection Gauge's Velocity Simulation Based on Pressure Differential
      Using Artificial Neural Networks.
AB  - Industrial pipelines must be inspected to detect typical failures, such as
      obstructions and deformations, during their lifetime. In the petroleum industry,
      the most used non-destructive technique to inspect buried pipelines is pigging.
      This technique consists of launching a Pipeline Inspection Gauge (PIG) inside the
      pipeline, which is driven by the pressure differential produced by fluid flow.
      The purpose of this work is to study the application of artificial neural
      networks to calculate the PIG's velocity based on the pressure differential. We
      launch a prototype PIG inside a testing pipeline, where this PIG gathers velocity
      data from an odometer-based system, while a supervisory system gathers pressure
      data from the testing pipeline. Then we train a Multilayer Perceptron (MLP) and a
      Nonlinear Autoregressive Network with eXogenous Inputs (NARX) network with the
      gathered data to predict velocity. The results suggest it is possible to use a
      neural network to model the PIG's velocity from pressure differential
      measurements. Our method is a new approach to the typical speed measurements
      based only on odometer, since the odometer is prone to fail and present poor
      results under some circumstances. Moreover, it can be used to provide redundancy,
      improving reliability of data obtained during the test.

PMID- 30216995
TI  - Faithful Families Cooking and Eating Smart and Moving for Health: Evaluation of a
      Community Driven Intervention.
AB  - Background: There is an increasing need to adapt and use community interventions
      to address modifiable behaviors that lead to poor health outcomes, like obesity,
      diabetes, and heart disease. Poor health outcomes can be tied to community-level
      factors, such as food deserts and individual behaviors, like sedentary
      lifestyles, consuming large portion sizes, and eating high-calorie fast food and
      processed foods. Methods: Through a social ecological approach with family,
      organization and community, the Faithful Families Cooking and Eating Smart and
      Moving for Health (FFCESMH) intervention was created to address these concerns in
      a rural South Carolina community. FFCESMH used gatekeepers to identify 18
      churches and four apartment complexes in low-income areas; 176 participants
      completed both pre- and post-survey measures. Results: Paired t-test measures
      found statistically significant change in participant perception of food security
      (0.39, p-value = 0.005, d = 0.22), self-efficacy with physical activity and
      healthy eating (0.26, p-value = 000, d = 0.36), and cooking confidence (0.17, p
      value = 0.01, d = 0.19). There was not significant change in cooking behaviors,
      as assessed through the Cooking Behaviors Scale. Conclusion: FFCESMH shows that a
      social ecological approach can be effective at increasing and improving
      individual healthy behaviors and addressing community-level factors in low-income
      rural communities.

PMID- 30216996
TI  - The Evaluation of Professional Divisions of Traditional Chinese Medicine in
      Taiwan through Patient Visit Records of 2012.
AB  - For decades, professional divisions have been represented as the main structural
      divisions in Western medicine throughout the world. In Taiwan, medical
      policymakers are also interested in designing professional divisions of
      traditional Chinese medicine (TCM). Therefore, this study evaluated the current
      status and potentiality of professional divisions of TCM in Taiwan using data
      from the year 2012 obtained from the National Health Insurance Research Database;
      the database provides information regarding age and gender of TCM physicians
      (TCMPs); total visit counts; contracted medical institution codes; groupings of
      diseases classified under International Classification of Diseases, Ninth
      Revision, Clinical Modification codes; numbers of children and female patients
      seeking treatment; and claim disposition codes used by each TCMP. The results
      indicated that there were 5522 TCMPs in 2012, and 4876 (90.3%) TCMPs practiced in
      primary clinics. The proportions of pediatric visits to these TCMPs were mostly
      below 0.2, and acupuncture or traumatology-related visit proportions were below
      0.5. Only a few of the studied Taiwan-based TCMPs practiced gynecology and
      pediatrics, but most of them performed "internal medicine", or "acupuncture" or
      "traumatology" treatments. Thus, the number of TCM specialists practicing
      gynecology or pediatrics is insufficient, indicating that a policy that forms
      professional divisions of TCM practitioners in Taiwan should be reconsidered.

PMID- 30216997
TI  - How a Communication Intervention in Zambia Re-Oriented Health Services to the
      Needs of the Least-Supported.
AB  - Despite decades of training health workers in communication, complaints from
      clients and communities about poor health worker attitudes abound. This was found
      to be so in Zambia where the More Mobilizing Access to Maternal Health Services
      in Zambia (MORE MAMaZ) program was trying to ensure the inclusion of under
      supported women in a community-based maternal and newborn health program in five
      intervention districts. Under-supported women suffer a disproportionate burden of
      child mortality and are poor users of health services. An exploratory small-scale
      qualitative survey involving nurses from training schools and health facilities
      found that nurses knew how to communicate well, but were selective with whom and
      in what circumstances they did this. In general, those who received the worst
      communication were under-supported and had low confidence-the very people who
      needed the best communication. An experiential training program was started to
      help health workers reflect on the reasons for their poor communication. The
      training was evaluated after 14 months using semi-structured interviews and focus
      group discussions with staff at participating health facilities. The results
      showed improved inclusion of under-supported women but also increased attendance
      generally for ante-natal clinics, deliveries and under-five clinics. Another
      outcome was improved communication between, and a sense of job satisfaction
      among, the health workers themselves. The program demonstrated an effective way
      to improve the inclusion and involvement of the least-supported women and girls.
      There are important lessons for other health programs that aim to operationalize
      the goals of the Global Strategy for Women's, Children's and Adolescent's Health,
      which include an emphasis on reaching every woman.

PMID- 30216998
TI  - Resistance of Escherichia coli in Turkeys after Therapeutic or Environmental
      Exposition with Enrofloxacin Depending on Flooring.
AB  - Gaining knowledge about the spread of resistance against antibacterial agents is
      a primary challenge in livestock farming. The purpose of this study was to test
      the effect of double antibiotic treatment (at days 10-14 and days 26-30) with
      enrofloxacin or solely environmental exposition (identical times, directly into
      the litter) on resistance against antibacterial agents in commensal Escherichia
      coli in comparison with the control (without treatment), depending on different
      flooring. A total of 720 Big 6 turkeys participated in three trials. Four
      different flooring designs were examined: An entire floor pen covered with
      litter, a floor pen with heating, a partially slatted flooring including 50%
      littered area, and a fully slatted flooring with a sand bath. A total of 864
      Escherichia coli isolates were obtained from cloacal swabs and poultry manure
      samples at days 2, 9, 15, 21, and 35. The broth microdilution method (MIC) was
      used to determine the resistance of isolates to enrofloxacin and ampicillin. A
      double antibiotic treatment with enrofloxacin reduced the proportion of
      susceptible Escherichia coli isolates significantly in all flooring designs.
      Simulation of water losses had no significant effect, nor did the flooring
      design. Ampicillin-resistant isolates were observed, despite not using
      ampicillin.

PMID- 30216999
TI  - Chromogenic Multiplex Immunohistochemistry Reveals Modulation of the Immune
      Microenvironment Associated with Survival in Elderly Patients with Lung
      Adenocarcinoma.
AB  - With underrepresentation of elderly patients with lung adenocarcinoma (LADC) in
      anti-PD-1/PD-L1 clinical trials, better understanding of the interplay of PD-L1
      and tumor-associated immune cells (TAICs) could assist clinicians in stratifying
      these patients for immunotherapy. One hundred and one patients with LADCs,
      stratified by age, were included for analysis of PD-L1 expression and density of
      TAICs expressing CD4, CD8, and CD33, by using multiplex chromogenic
      immunohistochemistry (IHC) assays and automated digital quantification. The
      CD4+/CD8+ ratio was significantly higher in elderly patients. In patients <75
      years, the density of CD4+, CD8+, and PD-L1 in TAICs showed a positive
      significant correlation with PD-L1 expression in tumor cells (TCs), while a lower
      correlation was observed in the elderly population. In the latter, a high
      CD4+/CD8+ ratio, and combined PD-L1 expression >=1% TCs with a low CD8+ density,
      low CD33+ density, and a high CD4+ density correlated to worse overall survival.
      We identified differences according to age in the CD4+/CD8+ ratio and in
      correlation between PD-L1 expression and the density of TAICs in LADC patients.
      Distinct groups of tumor microenvironments had an impact on the OS of elderly
      patients with LADC.

PMID- 30217000
TI  - Cell Type Influences Local Delivery of Biomolecules from a Bioinspired Apatite
      Drug Delivery System.
AB  - Recently, the benefit of step-wise sequential delivery of fibroblast growth
      factor-2 (FGF-2) and bone morphogenetic protein-2 from a bioinspired apatite drug
      delivery system on mouse calvarial bone repair was demonstrated. The thicknesses
      of the nanostructured poly-l-Lysine/poly-l-Glutamic acid polyelectrolyte
      multilayer (PEM) and the bone-like apatite barrier layer that make up the
      delivery system, were varied. The effects of the structural variations of the
      coating on the kinetics of cell access to a cytotoxic factor delivered by the
      layered structure were evaluated. FGF-2 was adsorbed into the outer PEM, and
      cytotoxic antimycin-A (AntiA) was adsorbed to the substrate below the barrier
      layer to detect the timing of the cell access. While MC3T3-E1 osteoprogenitor
      cells accessed AntiA after three days, the RAW 264.7 macrophage access occurred
      within 4 h, unless the PEM layer was removed, in which case the results were
      reversed. Pits were created in the coating by the RAW 264.7 macrophages and
      initiated delivery, while the osteoprogenitor cell access to drugs occurred
      through a solution-mediated coating dissolution, at junctions between the islands
      of crystals. Macrophage-mediated degradation is therefore a mechanism that
      controls drug release from coatings containing bioinspired apatite.

PMID- 30217001
TI  - Surface-Limited Electrodeposition of Continuous Platinum Networks on Highly
      Ordered Pyrolytic Graphite.
AB  - Continuous thin platinum nanoplatelet networks and thin films were obtained on
      the flat surface of highly ordered pyrolytic graphite (HOPG) by high
      overpotential electrodeposition. By increasing the deposition time, the
      morphology of the Pt deposits can be progressively tuned from isolated
      nanoplatelets, interconnected nanostructures, and thin large flat islands. The
      deposition is surface-limited and the thickness of the deposits, equivalent to 5
      to 12 Pt monolayers, is not time dependent. The presence of Pt (111) facets is
      confirmed by High Resolution Transmission Electron Microscopy (HRTEM) and
      evidence for the early formation of a platinum monolayer is provided by Scanning
      Transmission Electron Microscopy and Energy Dispersive X-rays Spectroscopy (STEM
      EDX) and X-ray Photoelectron Spectroscopy (XPS) analysis. The electroactivity
      towards the oxygen reduction reaction of the 2D deposits is also assessed,
      demonstrating their great potential in energy conversion devices where ultra-low
      loading of Pt via extended surfaces is a reliable strategy.

PMID- 30217002
TI  - Antimicrobial Features of Organic Functionalized Graphene-Oxide with Selected
      Amines.
AB  - (1) Background: Graphene oxide is a new carbon-based material that contains
      functional groups (carboxyl, hydroxyl, carbonyl, epoxy) and therefore can be
      easily functionalized with organic compounds of interest, yielding hybrid
      materials with important properties and applications. (2) Methods: Graphene oxide
      has been obtained by a modified Hummers method and activated by thionyl chloride
      in order to be covalently functionalized with amines. Thus obtained hybrid
      materials were characterized by infrared and Raman spectroscopy, elemental
      analysis and scanning electron microscopy and then tested for their antimicrobial
      and anti-biofilm activity. (3) Results: Eight amines of interest were used to
      functionalize grapheme oxide and the materials thus obtained were tested against
      Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive
      (Staphylococcus aureus) bacterial strainsin plankonic and biofilm growth state.
      Both amines, as well as the functionalized materials, exhibited anti-microbial
      features. Three to five functionalized graphene oxide materials exhibited
      improved inhibitory activity against planktonic strains as compared with the
      respective amines. In exchange, the amines alone proved generally more efficient
      against biofilm-embedded cells. (4) Conclusions: Such hybrid materials may have a
      wide range of potential use in biomedical applications.

PMID- 30217003
TI  - Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through
      the PI3K/Akt/GSK-3beta Pathway.
AB  - Cryptotanshinone (CTT) is a natural product and a quinoid diterpene isolated from
      the root of the Asian medicinal plant, Salvia miltiorrhizabunge. Notably, CTT has
      a variety of anti-cancer actions, including the activation of apoptosis, anti
      proliferation, and reduction in angiogenesis. We further investigated the anti
      cancer effects of CTT using MTS, LDH, and Annexin V assay, DAPI staining, cell
      cycle arrest, and Western blot analysis in NSCLC cell lines. NSCLC cells treated
      with CTT reduced cell growth through PI3K/Akt/GSK3beta pathway inhibition, G0/G1
      cell cycle arrest, and the activation of apoptosis. CTT induced an increase of
      caspase-3, caspase-9, poly-ADP-ribose polymerase (PARP), and Bax, as well as
      inhibition of Bcl-2, survivin, and cellular-inhibitor of apoptosis protein 1 and
      2 (cIAP-1 and -2). It also induced G0/G1 phase cell cycle arrest by decreasing
      the expression of the cyclin A, cyclin D, cyclin E, Cdk 2, and Cdk 4. These
      results highlight anti-proliferation the latent of CTT as natural therapeutic
      agent for NSCLC. Therefore, we investigated the possibility of CTT as an anti
      cancer agent by comparing with GF, which is a representative anti-cancer drug.

PMID- 30217004
TI  - Food Choice Priorities Change Over Time and Predict Dietary Intake at the End of
      the First Year of College Among Students in the U.S.
AB  - This study assessed food choice priorities (FCP) and associations with
      consumption of fruits and vegetables (FV), fiber, added sugars from non-beverage
      sources, and sugar-sweetened beverages (SSB) among college students. Freshmen
      from eight U.S. universities (N = 1149) completed the Food Choice Priorities
      Survey, designed for college students to provide a way to determine the factors
      of greatest importance regarding food choices, and the NCI Dietary Screener
      Questionnaire. Changes in FCP and dietary intake from fall 2015 to spring 2016
      were assessed. Multiple regression models examined associations between FCP and
      log-transformed dietary intake, controlling for sex, age, race, and BMI.
      Participant characteristics and FCP associations were also assessed. FCP
      importance changed across the freshmen year and significantly predicted dietary
      intake. The most important FCP were price, busy daily life and preferences, and
      healthy aesthetic. Students who endorsed healthy aesthetic factors (health,
      effect on physical appearance, freshness/quality/in season) as important for food
      choice, consumed more FV and fiber and less added sugar and SSB. Busy daily life
      and preferences (taste, convenience, routine, ability to feel full) predicted
      lower FV, higher added sugar, and higher SSB consumption. Price predicted lower
      FV, higher SSB, and more added sugar while the advertising environment was
      positively associated with SSB intake. FCP and demographic factors explained
      between 2%-17% of the variance in dietary intake across models. The strongest
      relationship was between healthy aesthetic factors and SSB (B = -0.37, p < 0.01).
      Self-rated importance of factors influencing food choice are related to dietary
      intake among students. Interventions that shift identified FCP may positively
      impact students' diet quality especially considering that some FCP increase in
      importance across the first year of college.

PMID- 30217005
TI  - Sanggenon C Stimulates Osteoblastic Proliferation and Differentiation, Inhibits
      Osteoclastic Resorption, and Ameliorates Prednisone-Induced Osteoporosis in
      Zebrafish Model.
AB  - Sanggenon C (SC), which is a natural flavonoid found in the stem bark of Cortex
      Mori, has been discovered to have the antioxidant, anti-inflammatory, and
      antitumor properties. However, its effect in osteoporosis has not yet been
      reported. In this research, the effect of SC on the proliferation of MC3T3-E1
      cells was evaluated by using the MTT assay. Alkaline phosphatase (ALP) activity
      and the mRNA expression of Runx2, Collagen I, OPG, and RANKL were examined. TRAP
      positive cell counting and bone resorption pits were adopted to observe the
      effect of SC on the formation and function of osteoclasts. Next, the mRNA level
      of TRAP, CTSK, NFATc1, and TRAF6 of osteoclasts were measured by real-time qPCR.
      In addition, the anti-osteoporosis activity of SC in vivo was evaluated in the
      zebrafish model. Our study indicated that SC exhibited a significant stimulatory
      effect on MC3T3-E1 cell proliferation at 1 to 10 MUM and caused an increase in
      ALP activity at 0.3 to 10 MUM. It could upregulate the expression of Runx2,
      Collagen I, and increases the OPG/RANKL ratio. Furthermore, SC was found to
      inhibit the formation and function of osteoclasts, which is demonstrated by a
      lower number of TRAP-positive multinuclear cells and a fewer area of bone
      resorption pits compared to the control group. TRAP, CTSK, and NFATc1 were
      downregulated in 0.3 to 10 MUM SC treated groups. In addition, 3 to 10 MUM SC
      also inhibited the expression of TRAF6 mRNA. When prednisone-induced zebrafish
      was treated with 0.3, 1, 3, and 10 MUM SC, higher mineralization of vertebrate
      column was discovered in a dose-dependent pattern, which suggests that SC could
      reverse the bone loss of zebrafish caused by prednisone. In summary, these
      findings indicated that SC has the potential to prevent or treat osteoporosis.

PMID- 30217006
TI  - Targeting the Bacterial Protective Armour; Challenges and Novel Strategies in the
      Treatment of Microbial Biofilm.
AB  - Infectious disease caused by pathogenic bacteria continues to be the primary
      challenge to humanity. Antimicrobial resistance and microbial biofilm formation
      in part, lead to treatment failures. The formation of biofilms by nosocomial
      pathogens such as Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P.
      aeruginosa), and Klebsiella pneumoniae (K. pneumoniae) on medical devices and on
      the surfaces of infected sites bring additional hurdles to existing therapies. In
      this review, we discuss the challenges encountered by conventional treatment
      strategies in the clinic. We also provide updates on current on-going research
      related to the development of novel anti-biofilm technologies. We intend for this
      review to provide understanding to readers on the current problem in health-care
      settings and propose new ideas for new intervention strategies to reduce the
      burden related to microbial infections.

PMID- 30217008
TI  - Crystalline/Amorphous Blend Identification from Cobalt Adsorption by Layered
      Double Hydroxides.
AB  - In this study, the adsorption behavior of CaAl-Cl layered double hydroxide (CaAl
      Cl-LDH) with a controlled pH value (pH = 6) on Co(II) ions ([Co] = 8 mM) is
      investigated. The comprehensively accepted mechanism of cobalt adsorption on LDH
      is considered to be co-precipitation, and the final adsorbed products are
      normally crystalline Co-LDH. One unanticipated finding is that
      crystalline/amorphous blends are found in the X-ray diffraction (XRD) pattern of
      Co-adsorbed LDH. To shed light on the adsorption products and the mechanisms in
      the adsorption process of Co(II) in an aqueous solution by CaAl-Cl-LDH, a series
      of testing methods including Fourier-transform infrared spectroscopy (FT-IR),
      Scanning electron microscope (SEM), High-resolution transmission electron
      microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), and inductively
      coupled plasma (ICP) are applied to clarify the interaction between cobalt and
      CaAl-Cl-LDH. According to the comprehensive analysis, the formation of the
      crystalline/amorphous blends corresponds to two adsorption mechanisms. The
      crystalline phases are identified as Co6Al2CO3(OH)16.4H2O, which is attributed to
      the co-precipitation process occurring in the interaction between Co(II) and CaAl
      Cl-LDH. The formation of the amorphous phases is due to surface complexation on
      amorphous Al(OH)3 hydrolyzed from CaAl-Cl-LDH.

PMID- 30217007
TI  - The Role of Signal Transducer and Activator of Transcription 3 (STAT3) and Its
      Targeted Inhibition in Hematological Malignancies.
AB  - Signal transducer and activator of transcription 3 (STAT3), a member of the STAT
      protein family, can be phosphorylated by receptor-associated Janus kinases (JAKs)
      in response to stimulation by cytokines and growth factors. It forms homo- or
      heterodimers that can translocate to the cell nucleus where they act as
      transcription activators. Constitutive activation of STAT3 has been found to be
      associated with initiation and progression of various cancers. It can exert
      proliferative as well as anti-apoptotic effects. This review focuses on the role
      of STAT3 in pathogenesis i.e., proliferation, differentiation, migration, and
      apoptosis of hematological malignancies viz. leukemia, lymphoma and myeloma, and
      briefly highlights the potential therapeutic approaches developed against STAT3
      activation pathway.

PMID- 30217009
TI  - Peptide Mimics of the Ribosomal P Stalk Inhibit the Activity of Ricin A Chain by
      Preventing Ribosome Binding.
AB  - Ricin A chain (RTA) depurinates the sarcin/ricin loop (SRL) by interacting with
      the C-termini of the ribosomal P stalk. The ribosome interaction site and the
      active site are located on opposite faces of RTA. The interaction with P proteins
      allows RTA to depurinate the SRL on the ribosome at physiological pH with an
      extremely high activity by orienting the active site towards the SRL. Therefore,
      if an inhibitor disrupts RTA-ribosome interaction by binding to the ribosome
      binding site of RTA, it should inhibit the depurination activity. To test this
      model, we synthesized peptides mimicking the last 3 to 11 amino acids of P
      proteins and examined their interaction with wild-type RTA and ribosome binding
      mutants by Biacore. We measured the inhibitory activity of these peptides on RTA
      mediated depurination of yeast and rat liver ribosomes. We found that the
      peptides interacted with the ribosome binding site of RTA and inhibited
      depurination activity by disrupting RTA-ribosome interactions. The shortest
      peptide that could interact with RTA and inhibit its activity was four amino
      acids in length. RTA activity was inhibited by disrupting its interaction with
      the P stalk without targeting the active site, establishing the ribosome binding
      site as a new target for inhibitor discovery.

PMID- 30217010
TI  - Natural Products from Actinobacteria Associated with Fungus-Growing Termites.
AB  - The chemical analysis of insect-associated Actinobacteria has attracted the
      interest of natural product chemists in the past years as bacterial-produced
      metabolites are sought to be crucial for sustaining and protecting the insect
      host. The objective of our study was to evaluate the phylogeny and bioprospecting
      of Actinobacteria associated with fungus-growing termites. We characterized 97
      Actinobacteria from the gut, exoskeleton, and fungus garden (comb) of the fungus
      growing termite Macrotermes natalensis and used two different bioassays to assess
      their general antimicrobial activity. We selected two strains for chemical
      analysis and investigated the culture broth of the axenic strains and fungus
      actinobacterium co-cultures. From these studies, we identified the previously
      reported PKS-derived barceloneic acid A and the PKS-derived rubterolones.
      Analysis of culture broth yielded a new dichlorinated diketopiperazine derivative
      and two new tetracyclic lanthipeptides, named rubrominins A and B. The discussed
      natural products highlight that insect-associated Actinobacteria are highly
      prolific natural product producers yielding important chemical scaffolds urgently
      needed for future drug development programs.

PMID- 30217011
TI  - Development and Application of Novel Caregiver Hygiene Behavior Measures Relating
      to Food Preparation, Handwashing, and Play Environments in Rural Kenya.
AB  - Exposure to fecal pathogens results in both acute and chronic sequalae in young
      children. Diarrhea causes nearly 20% of all under-five mortality, while even sub
      clinical enteric infections may lead to growth shortfalls. Stunting affects
      nearly 165 million children globally and results in lifelong and
      intergenerational effects for the world's poorest populations. Caregiver hygiene
      behaviors, such as those surrounding handwashing and food preparation, play a
      critical role in exposure to fecal pathogens; standard metrics to assess these
      behaviors are warranted to provide a means of quantifying the impact these
      behaviors have on enteric infections and to evaluate the success or failure of
      interventions and programs. This paper documents the development of three novel
      caregiver hygiene behavior measures: hygienic food preparation and storage,
      handwashing at key times, and provision of a safe play environment for children
      under two years. We developed these measures using formative qualitative work,
      survey creation and deployment theoretically underpinned by the COM-B model of
      behavior change, and exploratory and confirmatory factor analysis. The final
      measure for hygienic food preparation and storage includes 10 items across two
      factors; the final measure for handwashing at key times includes 15 items across
      three factors; and the final measure for safe play environment contains 13 items
      across three factors. Future researchers may employ these measures to assess
      caregiver behaviors in other populations, identify specific behavioral dimensions
      that should be the focus of interventions, and evaluate interventions and
      programs.

PMID- 30217012
TI  - Identification and Characterization of microRNAs during Retinoic Acid-Induced
      Regeneration of a Molluscan Central Nervous System.
AB  - Retinoic acid (RA) is the biologically active metabolite of vitamin A and has
      become a well-established factor that induces neurite outgrowth and regeneration
      in both vertebrates and invertebrates. However, the underlying regulatory
      mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the
      past decade, microRNAs have emerged as important regulators of nervous system
      development and regeneration, and have been shown to contribute to processes such
      as neurite sprouting. However, few studies have demonstrated the role of miRNAs
      in RA-induced neurite sprouting. By miRNA sequencing analysis, we identify 482
      miRNAs in the regenerating central nervous system (CNS) of the mollusc
      Lymnaeastagnalis, 219 of which represent potentially novel miRNAs. Of the
      remaining conserved miRNAs, 38 show a statistically significant up- or
      downregulation in regenerating CNS as a result of RA treatment. We further
      characterized the expression of one neuronally-enriched miRNA upregulated by RA,
      miR-124. We demonstrate, for the first time, that miR-124 is expressed within the
      cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR
      124 expression within the growth cones of cultured ciliary motorneurons (pedal
      A), whereas expression in the growth cones of another class of respiratory
      motorneurons (right parietal A) was absent in vitro. These findings support our
      hypothesis that miRNAs are important regulators of retinoic acid-induced neuronal
      outgrowth and regeneration in regeneration-competent species.

PMID- 30217013
TI  - The Degradation Properties of MgO Whiskers/PLLA Composite In Vitro.
AB  - In this study, composite films of stearic acid-modified magnesium oxide whiskers
      (Sa-w-MgO)/poly-l-lactic acid (PLLA) were prepared through solution casting, and
      the in vitro degradation properties and cytocompatibility of the composites with
      different whisker contents were investigated. The results showed that the
      degradation behavior of the composite samples depended significantly on the
      whisker content, and the degradation rate increased with the addition of MgO
      content. Furthermore, the degradation of the composites with higher contents of
      whiskers was influenced more severely by the hydrophilicity and pH value, leading
      to more final weight loss, but the decomposition rate decreased gradually.
      Furthermore, the pH value of the phosphate buffer solution (PBS) was obviously
      regulated by the dissolution of MgO whiskers through neutralization of the acidic
      product of PLLA degradation. The cytocompatibility of the composites also
      increased remarkably, as determined from the cell viability results, and was
      higher than that of PLLA at the chosen whisker content. This was beneficial for
      the cell affinity of the material, as it notably led to an enhanced
      biocompatibility of the PLLA, in favor of promoting cell proliferation, which
      significantly improved its bioactivity, as well.

PMID- 30217014
TI  - Maize Dwarf Mosaic Virus: From Genome to Disease Management.
AB  - Maize dwarf mosaic virus (MDMV) is a serious maize pathogen, epidemic worldwide,
      and one of the most common virus diseases for monocotyledonous plants, causing up
      to 70% loss in corn yield globally since 1960. MDMV belongs to the genus
      Potyvirus (Potyviridae) and was first identified in 1964 in Illinois in corn and
      Johnsongrass. MDMV is a single stranded positive sense RNA virus and is
      transmitted in a non-persistent manner by several aphid species. MDMV is amongst
      the most important virus diseases in maize worldwide. This review will discuss
      its genome, transmission, symptomatology, diagnosis and management. Particular
      emphasis will be given to the current state of knowledge on the diagnosis and
      control of MDMV, due to its importance in reducing the impact of maize dwarf
      mosaic disease, to produce an enhanced quality and quantity of maize.

PMID- 30217015
TI  - Blood Coagulation Testing Smartphone Platform Using Quartz Crystal Microbalance
      Dissipation Method.
AB  - Blood coagulation function monitoring is important for people who are receiving
      anticoagulation treatment and a portable device is needed by these patients for
      blood coagulation self-testing. In this paper, a novel smartphone based blood
      coagulation test platform was proposed. It was developed based on parylene-C
      coated quartz crystal microbalance (QCM) dissipation measuring and analysis. The
      parylene-C coating constructed a robust and adhesive surface for fibrin
      capturing. The dissipation factor was obtained by measuring the frequency
      response of the sensor. All measured data were sent to a smartphone via Bluetooth
      for dissipation calculation and blood coagulation results computation. Two major
      coagulation indexes, activated partial thromboplastin time (APTT) and prothrombin
      time (PT) were measured on this platform compared with results by a commercial
      hemostasis system in a clinical laboratory. The measurement results showed that
      the adjusted R-square (R2) value for APTT and PT measurements were 0.985 and
      0.961 respectively. The QCM dissipation method for blood coagulation measurement
      was reliable and effective and the platform together with the QCM dissipation
      method was a promising solution for point of care blood coagulation testing.

PMID- 30217016
TI  - Concatenation of Human Connexin26 (hCx26) and Human Connexin46 (hCx46) for the
      Analysis of Heteromeric Gap Junction Hemichannels and Heterotypic Gap Junction
      Channels.
AB  - Gap junction channels and hemichannels formed by concatenated connexins were
      analyzed. Monomeric (hCx26, hCx46), homodimeric (hCx46-hCx46, hCx26-hCx26), and
      heterodimeric (hCx26-hCx46, hCx46-hCx26) constructs, coupled to GFP, were
      expressed in HeLa cells. Confocal microscopy showed that the tandems formed gap
      junction plaques with a reduced plaque area compared to monomeric hCx26 or hCx46.
      Dye transfer experiments showed that concatenation allows metabolic transfer.
      Expressed in Xenopus oocytes, the inside-out patch-clamp configuration showed
      single channels with a conductance of about 46 pS and 39 pS for hemichannels
      composed of hCx46 and hCx26 monomers, respectively, when chloride was replaced by
      gluconate on both membrane sides. The conductance was reduced for hCx46-hCx46 and
      hCx26-hCx26 homodimers, probably due to the concatenation. Heteromerized
      hemichannels, depending on the connexin-order, were characterized by substates at
      26 pS and 16 pS for hCx46-hCx26 and 31 pS and 20 pS for hCx26-hCx46. Because of
      the linker between the connexins, the properties of the formed hemichannels and
      gap junction channels (e.g., single channel conductance) may not represent the
      properties of hetero-oligomerized channels. However, should the removal of the
      linker be successful, this method could be used to analyze the electrical and
      metabolic selectivity of such channels and the physiological consequences for a
      tissue.

PMID- 30217017
TI  - Targeted Genomic Screen Reveals Focal Long Non-Coding RNA Copy Number Alterations
      in Cancer Cell Lines.
AB  - The landscape of somatic copy-number alterations (SCNAs) affecting long non
      coding RNAs (lncRNAs) in human cancers remains largely unexplored. While the
      majority of lncRNAs remain to be functionally characterized, several have been
      implicated in cancer development and metastasis. Considering the plethora of
      lncRNAs genes that have been currently reported, it is conceivable that many more
      lncRNAs might function as oncogenes or tumor suppressor genes. We devised a
      strategy to detect focal lncRNA SCNAs using a custom DNA microarray platform
      probing 10,519 lncRNA genes. By screening a panel of 80 cancer cell lines, we
      detected numerous focal aberrations targeting one or multiple lncRNAs without
      affecting neighboring protein-coding genes. These focal aberrations are highly
      suggestive for a tumor suppressive or oncogenic role of the targeted lncRNA gene.
      Although functional validation remains an essential step in the further
      characterization of the involved candidate cancer lncRNAs, our results provide a
      direct way of prioritizing candidate lncRNAs that are involved in cancer
      pathogenesis.

PMID- 30217019
TI  - Effects of Heat-Treatment Temperature on the Microstructure and Mechanical
      Properties of Steel by MgO Nanoparticle Additions.
AB  - The characteristics and formation mechanisms of intragranular acicular ferrite
      (IAF) in steel with MgO nanoparticle additions were systematically investigated
      for different isothermal heat-treatment temperatures, and its influence on
      mechanical properties was also clarified. The results indicate that the
      inclusions were finely dispersed and refined after adding MgO nanoparticles. In
      addition, with decreasing heat-treatment temperature, the microstructure changed
      from grain boundary ferrite (GBF) and polygonal ferrite (PF) to intragranular
      acicular ferrite. Moreover, the steel with MgO additions had excellent mechanical
      properties in the temperature range of 973 to 823 K and an average Charpy
      absorbed energies value of around 174 J at 873 K due to the significant
      refinement of the microstructure and nucleation of intragranular acicular
      ferrite.

PMID- 30217018
TI  - Identification of Novel Subcellular Localization and Trafficking of HIV-1 Nef
      Variants from Reference Strains G (F1.93.HH8793) and H (BE.93.VI997).
AB  - The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef, plays an
      essential role in disease progression and pathogenesis via hijacking the host
      cellular membrane-trafficking machinery. Interestingly, HIV-1 group-M subtypes
      display differences in the rate of disease progression. However, few reports
      investigated how the cellular behaviors and activities of Nef isolates from
      reference strains may differ between HIV-1 group-M subtypes. Here, we
      characterize how differing cellular distributions of Nef proteins across group-M
      subtypes may impact protein function using immunofluorescence microscopy and flow
      cytometric analysis. We demonstrate that Nef variants isolated from HIV-1 group-M
      subtypes display differences in expression, with low expressing Nef proteins from
      reference strains of subtypes G (F1.93.HH8793) and H (BE.93.VI997) also
      displaying decreased functionality. Additionally, we demonstrate variations in
      the subcellular distribution and localization of these Nef proteins. Nef from
      subtype G (F1.93.HH8793) and H (BE.93.VI997) reference strains also failed to
      colocalize with the trans-Golgi network, and were not differentially localized to
      cellular markers of multivesicular bodies or lysosomes. Strikingly, our results
      demonstrate that HIV-1 Nef proteins from reference strains G (F1.93.HH8793) and H
      (BE.93.VI997) highly colocalize with labeled mitochondrial compartments.

PMID- 30217020
TI  - A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and
      Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation.
AB  - We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts
      anticancer activity through p53 acetylation in MCF-7 human breast cancer cells.
      We investigated the anticancer activity of MHY2256 against hormone-related
      cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256
      were shown to be much lower than those of salermide, a well-known SIRT inhibitor.
      Furthermore, MHY2256 significantly reduced the protein expression and activities
      of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256
      markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa
      cancer cells. During the experimental period, there was no significant change in
      the body weight of mice treated with MHY2256. A detailed analysis of the
      sensitization mechanisms of Ishikawa cells revealed that late apoptosis was
      largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and
      reduced the number of cell cyclic-related proteins, suggesting that apoptosis by
      MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased
      by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in
      MHY2256 sensitization in Ishikawa cells. We also detected a significant increase
      in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256
      treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth
      and weight without apparent side effects. These results suggest that MHY2256
      exerts its anticancer activity through p53 acetylation in endometrial cancer and
      can be used for targeting hormone-related cancers.

PMID- 30217021
TI  - Associations of Physical Activity and Sedentary Time in Primary School Children
      with Their Parental Behaviors and Supports.
AB  - BACKGROUND: The associations of objectively evaluated moderate-to-vigorous
      physical activity (MVPA) and sedentary time between primary school children and
      their fathers or mothers have not been fully understood. Therefore, we tested the
      associations in children. Methods: The participants were first to sixth grade
      boys (n = 166, 9.4 +/- 1.6 years) and girls (n = 202, 9.4 +/- 1.6 years) and
      their parents (fathers, n = 123 and mothers, n = 321). MVPA and sedentary time
      were measured using triaxial accelerometry. The relationship between parental
      support which was assessed by self-reported questionnaire and children's MVPA was
      also examined. RESULTS: MVPA in the children was positively correlated with
      maternal MVPA after adjustment for the children's gender, grade, body mass index
      z-score, paternal or maternal age, and school (p < 0.001). However, paternal or
      maternal sedentary time and paternal MVPA showed no significant association with
      sedentary time or MVPA in children. On the other hand, the percentage of MVPA in
      children who spent more time with their mothers on weekends was significantly
      lower than those who spent less time (p = 0.034). Children whose mothers watched
      their sports events had a significantly higher percentage of MVPA than those
      whose mothers did not watch these events (p = 0.008). There were no associations
      between children's MVPA and paternal support. CONCLUSIONS: The findings of this
      study demonstrate the significance of maternal MVPA and support.

PMID- 30217022
TI  - User Experiences of Prescription and Over-The-Counter Drug Abuse in Aden City,
      Yemen.
AB  - Khat chewing is commonplace in Yemen, but little else is known about the misuse
      of other drugs, especially how such misuse may intersect with Khat use. The aim
      of this study was to investigate misuse of prescription and over-the-counter
      (OTC) drugs in community pharmacies in Aden city, from the users' perspective. A
      qualitative in-depth-interview study was undertaken with fifteen known or
      suspected drug misusers, recruited through community pharmacies. Thematic
      analysis was used to identify the main emergent themes around experience of
      prescription and OTC drug misuse. The majority of interviewees were male (n =
      11/15) with an age range of 21-40 years. Benzodiazepines, Tramadol, and
      Ketoprofen were the most commonly misused drugs. Four main themes were
      identified: Experience sought with drugs; awareness of problematic drug use;
      pattern and methods of misuse; and the role of healthcare professionals in
      responding to misuse. The study highlighted different issues, such as the
      practice of mixing different OTC and prescription drugs with Khat to heighten the
      effects or manage associated pain, and drug misuse by females and by health care
      professionals. The study also suggested that physicians and pharmacists fear
      counselling such people, probably with the risk of violence as a contributory
      factor.

PMID- 30217023
TI  - Overexpression of OsGID1 Enhances the Resistance of Rice to the Brown Planthopper
      Nilaparvata lugens.
AB  - Gibberellins (GAs) play pivotal roles in plant growth and development, and in
      defenses against pathogens. Thus far, how the GA-mediated signaling pathway
      regulates plant defenses against herbivores remains largely unknown. In this
      study, we cloned the rice GA receptor gene OsGID1, whose expression was induced
      by damage from the brown planthopper (BPH) Niaparvata lugens, mechanical
      wounding, and treatment with salicylic acid (SA), but not jasmonic acid. The
      overexpression of OsGID1 (oe-GID1) decreased BPH-induced levels of SA, H2O2, and
      three SA-pathway-related WRKY transcripts, but enhanced BPH-induced levels of
      ethylene. Bioassays in the laboratory revealed that gravid BPH females preferred
      to feed and lay eggs on wild type (WT) plants than on oe-GID1 plants. Moreover,
      the hatching rate of BPH eggs on oe-GID1 plants was significantly lower than that
      on WT plants. In the field, population densities of BPH adults and nymphs were
      consistently and significantly lower on oe-OsGID1 plants than on WT plants. The
      increased resistance in oe-GID1 plants was probably due to the increased lignin
      level mediated by the GA pathway, and to the decrease in the expression of the
      three WRKY genes. Our findings illustrated that the OsGID1-mediated GA pathway
      plays a positive role in mediating the resistance of rice to BPH.

PMID- 30217024
TI  - Contribution to Reduce the Influence of the Free Sliding Edge on Compression
      After-Impact Testing of Thin-Walled Undamaged Composites Plates.
AB  - Standard Compression-After-Impact test devices show a weakening effect on thin
      walled specimens due to a free panel edge that is required for compression. As a
      result, thin-walled undamaged samples do not break in the free measuring area but
      near the free edge and along the supports. They also show a strength reduction
      due to the free edge which can become potentially relevant for very weakly
      damaged panels. In order to reduce the free edge influence on the measured
      strength, a modified Compression-After-Impact test device has been developed. In
      an experimental investigation with carbon fiber reinforced plastics, the modified
      device is compared with a standard device. It is shown that thin-walled undamaged
      specimens investigated with the modified device now mainly break within the free
      measuring area and no longer at the free edge and along the bearings as it is the
      case for standard test devices. The modified device does not cause a free edge
      weakening effect in comparison to standard devices. The modified device is
      therefore more suitable for determining the compression strengths of undamaged
      thin-walled composite plates.

PMID- 30217025
TI  - A New Concept to Secure Food Safety Standards against Fusarium Species and
      Aspergillus Flavus and Their Toxins in Maize.
AB  - Commercial maize hybrids are exposed to different degrees of ear infection by
      toxigenic fungal species and toxin contamination. Their resistance to different
      fungi and toxin relationships are largely unknown. Without this knowledge,
      screening and breeding are not possible for these pathogens. Seven- to tenfold
      differences were found in resistance to Fusarium spp., and there was a five-fold
      difference in ear coverage (%) in response to A. flavus. Three hybrids of the
      twenty entries had lower infection severity compared with the general means for
      toxigenic species. Three were highly susceptible to each, and 14 hybrids reacted
      differently to the different fungi. Differences were also observed in the toxin
      content. Again, three hybrids had lower toxin content in response to all
      toxigenic species, one had higher values for all, and 16 had variable resistance
      levels. Correlations between infection severity and deoxynivalenol (DON) content
      were 0.95 and 0.82 (p = 0.001) for F. graminearum and F. culmorum, respectively.
      For fumonisin and F. verticillioides ear rot, the Pearson correlation coefficient
      (r) was 0.45 (p = 0.05). Two independent isolates with different aggressiveness
      were used, and their mean X values better described the resistance levels. This
      increased the reliability of the data. With the introduction of this
      methodological concept (testing the resistance levels separately for different
      fungi and with two isolates independently), highly significant resistance
      differences were found. The resistance to different fungal species correlated
      only in certain cases; thus, each should be tested separately. This is very
      useful in registration tests and post-registration screening and breeding. This
      would allow a rapid increase in food and feed safety.

PMID- 30217026
TI  - Accuracy Evaluation of Dense Matching Techniques for Casting Part Dimensional
      Verification.
AB  - Product optimization for casting and post-casting manufacturing processes is
      becoming compulsory to compete in the current global manufacturing scenario.
      Casting design, simulation and verification tools are becoming crucial for
      eliminating oversized dimensions without affecting the casting component
      functionality. Thus, material and production costs decrease to maintain the
      foundry process profitable on the large-scale component supplier market. New
      measurement methods, such as dense matching techniques, rely on surface texture
      of casting parts to enable the 3D dense reconstruction of surface points without
      the need of an active light source as usually applied with 3D scanning optical
      sensors. This paper presents the accuracy evaluation of dense matching based
      approaches for casting part verification. It compares the accuracy obtained by
      dense matching technique with already certified and validated optical measuring
      methods. This uncertainty evaluation exercise considers both artificial targets
      and key natural points to quantify the possibilities and scope of each
      approximation. Obtained results, for both lab and workshop conditions, show that
      this image data processing procedure is fit for purpose to fulfill the required
      measurement tolerances for casting part manufacturing processes.

PMID- 30217027
TI  - Zika Virus Vaccines: Challenges and Perspectives.
AB  - Zika virus is an arbovirus that has rapidly spread within the Americas since
      2014, presenting a variety of clinical manifestations and neurological
      complications resulting in congenital malformation, microcephaly, and possibly,
      in male infertility. These significant clinical manifestations have led
      investigators to develop several candidate vaccines specific to Zika virus. In
      this review we describe relevant targets for the development of vaccines specific
      for Zika virus, the development status of various vaccine candidates and their
      different platforms, as well as their clinical progression.

PMID- 30217029
TI  - The Beneficial Effect of Proanthocyanidins and Icariin on Biochemical Markers of
      Bone Turnover in Rats.
AB  - Nutrition is an important factor that influences bone metabolism, the endocrine
      and/or paracrine system, and bone-active mineral elements homeostasis. We studied
      antiosteoporotic effects of grape seed proanthocyanidins extract, icariin or
      alendronate (ALN) in retinoic acid-induced (13cRA) bone loss in rats.
      Proanthocyanidins and icariin have beneficial effects on bone health; they have
      improved the bone weight reduction, the length and the diameter of the bone,
      calcium, and phosphorus content in bone ash, bone mineral density (BMD), the
      biochemical markers of bone turnover and uterus atrophy induced by 13cRA. All
      results suggest that proanthocyanidins and icariin reverse osteoporosis in 13cRA
      rats by stimulating bone formation or regulating bone resorption by their
      antioxidative and estrogenic-like activity without toxic side-effects observed in
      ALN treatment.

PMID- 30217030
TI  - Composition, Structure and Morphology Evolution of Octadecylamine (ODA)-Reduced
      Graphene Oxide and Its Dispersion Stability under Different Reaction Conditions.
AB  - Octadecylamine (ODA) can solve the aggregation problem of graphene sheets in the
      chemical exfoliation method. However, no attempts have been made to investigate
      the evolution of ODA-reduced graphene oxide (ORGO) with reaction conditions and
      the modification mechanism, which is the core problem to realize the controllable
      production and practical application of graphene. In this study, we treated
      graphene oxide (GO) with ODA under different reaction conditions to prepare ORGO.
      Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy,
      atomic force microscopy, Raman spectroscopy, thermogravimetric analysis (TGA),
      and UV-vis spectrophotometry were employed to analyze the composition, structure,
      morphology and characteristics of the as-prepared graphene sheets. The results
      showed that the reduction reaction could occur under mild conditions, but the
      edge grafting reaction could only be activated by a higher temperature. Moreover,
      the ORGO created at 80  degrees C for 5 h and 120  degrees C for 0.5 h exhibited
      the optimized properties, both excellent dispersing stability and high heat
      resisting property, since they had more edge grafting chains and a suitable
      reduction degree.

PMID- 30217031
TI  - Dose-Response Relationship between Exercise Duration and Executive Function in
      Older Adults.
AB  - This study aimed to determine the dose-response relationship between exercise
      duration and task switching in older adults. Acute moderate intensity aerobic
      exercise for 20 min resulted in shorter response times than control and 10-min
      sessions in the heterogeneous, non-switch, and switch conditions, but not in the
      homogeneous condition. Additionally, linear and cubic trends between exercise
      duration and global switching performance as well as local switching performance
      were revealed with faster times being predicted by longer duration exercise;
      however, the cubic relationship resulted in performance following the 45-min
      session being not significantly different from the other three sessions. Acute
      aerobic moderate intensity exercise for 20 min is an effective duration to
      improve task switching. Although a longer duration of exercise is not optimal for
      benefiting task switching, it does not harm task switching in older adults and
      hence may be of value for other health-related reasons.

PMID- 30217028
TI  - Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced
      by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and
      Network Pharmacology Study.
AB  - Oxidative stress, defined as a disequilibrium between pro-oxidants and
      antioxidants, can result in histopathological lesions with a broad spectrum,
      ranging from asymptomatic hepatitis to hepatocellular carcinoma in an
      orchestrated manner. Although cells are equipped with sophisticated strategies to
      maintain the redox biology under normal conditions, the abundance of redox
      sensitive xenobiotics, such as medicinal ingredients originated from herbs or
      animals, can dramatically invoke oxidative stress. Growing evidence has
      documented that the hepatotoxicity can be triggered by traditional Chinese
      medicine (TCM) during treating various diseases. Meanwhile, TCM-dependent hepatic
      disorder represents a strong correlation with oxidative stress, especially the
      persistent accumulation of intracellular reactive oxygen species. Of note, since
      TCM-derived compounds with their modulated targets are greatly diversified among
      themselves, it is complicated to elaborate the potential pathological mechanism.
      In this regard, data mining approaches, including network pharmacology and
      bioinformatics enrichment analysis have been utilized to scientifically disclose
      the underlying pathogenesis. Herein, top 10 principal TCM-modulated targets for
      oxidative hepatotoxicity including superoxide dismutases (SOD), malondialdehyde
      (MDA), glutathione (GSH), reactive oxygen species (ROS), glutathione peroxidase
      (GPx), Bax, caspase-3, Bcl-2, nuclear factor (erythroid-derived 2)-like 2 (Nrf2),
      and nitric oxide (NO) have been identified. Furthermore, hepatic metabolic
      dysregulation may be the predominant pathological mechanism involved in TCM
      induced hepatotoxic impairment.

PMID- 30217032
TI  - Are Engaged Workaholics Protected against Job-Related Negative Affect and Anxiety
      before Sleep? A Study of the Moderating Role of Gender.
AB  - Although the interplay between workaholism and work engagement could explain
      several open questions regarding the Heavy Work Investment (HWI) phenomenon, few
      studies have addressed this issue. Thus, with the purpose of filling this
      literature gap, the present study aimed at examining a model where job-related
      negative affect mediates the relationship between the interplay of workaholism
      and work engagement, and anxiety before sleep. Since gender could have a role in
      the way the interplay would impact on the theorized model, we also hypothesized a
      moderated role of gender on the specific connection concerning the interplay
      between workaholism and work engagement, in relation to job-related negative
      affect. Conditional process analysis was conducted on a sample of 146
      participants, balanced for gender. Results supported the mediating model and
      indicated the presence of a moderated role of gender, such that engaged
      workaholic women reported significantly less job-related negative affect than
      disengaged workaholic women. On the contrary, the interplay between workaholism
      and work engagement did not seem significant for men. Results are discussed in
      light of the limitations and future directions of the research in this field, as
      well as the ensuing practical implications.

PMID- 30217033
TI  - Preparation and Characterization of Macroalgae Biochar Nanomaterials with Highly
      Efficient Adsorption and Photodegradation Ability.
AB  - In this study, carbonized kelp biochar (AKB) modified by KOH impregnation and
      photocatalytic Bi2MoO6/AKB composite (BKBC) nanomaterials were the first time
      successfully synthesized for efficient removal of dyes in aqueous solution. BET,
      XRD, FT-IR, and SEM were employed to characterize as-prepared samples. UV-vis and
      other test results indicated that the removal efficiency of methylene blue (MB)
      was 61.39% and 94.12% for BKBC and AKB, respectively, which was up to 13 times
      and 20 times higher in comparison with pure Bi2MoO6 (PBM). In addition, the
      equilibrium adsorption capacity of MB could reach up to 324.1 mg/g for AKB. This
      high dyes adsorption performance could be likely attributed to its high specific
      surface area (507.177 m2/g) and its abundant presence of various functional
      groups such as -OH and =C-H on AKB. Particularly, the existing of amorphous
      carbon and transition metal oxides, such as Fe2O3 and Mn5O8, could be beneficial
      for the photodegradation of MB for AKB. Meanwhile, experimental data indicated
      that adsorption kinetics complied with the pseudo-second order model well, and
      all of the tests had satisfactory results in terms of the highly efficient
      adsorption and photodegradation activity of AKB nanomaterials, which suggested
      its great potential in wastewater treatment.

PMID- 30217035
TI  - An Active Lifestyle Reinforces the Effect of a Healthy Diet on Cognitive
      Function: A Population-Based Longitudinal Study.
AB  - The joint effect of diet and leisure activity on cognitive function remains
      unknown. We aimed to verify the hypothesis that an active lifestyle reinforces
      the effect of the Nordic Prudent Dietary Pattern (NPDP) on cognitive function. A
      total of 2223 dementia-free Swedish adults aged >=60 with Mini-Mental State
      Examination (MMSE) scores >=27 were followed for an average of 6 years. MMSE was
      tested during follow-ups. Diet was assessed by food frequency questionnaire. The
      NPDP index was calculated and tertiled (low, moderate, and high adherence).
      Participation in physical, mental and social activities was trichotomised (low,
      moderate, and intense). An active lifestyle was defined based on the
      participation in each activity. Data were analyzed using mixed-effects models.
      Moderate-to-high adherence to NPDP was associated with a reduced decline in the
      MMSE score (beta: 0.19, 95% Confidence Interval (CI): 0.14-0.24). This
      association became stronger when combined with moderate-to-intense physical
      (beta: 0.34, 95% CI: 0.2-0.45), mental (beta: 0.29, 95% CI: 0.21-0.37), or social
      (beta: 0.27, 95% CI: 0.19-0.34) activities. An active lifestyle strengthened the
      effect of NPDP on cognitive function by two times, and further lowered risk of
      MMSE decline by 30%. Thus, an active lifestyle reinforces the effect of a healthy
      diet on preserved cognitive function, and further decreases the risk of cognitive
      decline.

PMID- 30217034
TI  - Contribution of HIV Infection, AIDS, and Antiretroviral Therapy to Exocrine
      Pathogenesis in Salivary and Lacrimal Glands.
AB  - The structure and function of exocrine glands are negatively affected by human
      immunodeficiency virus (HIV) infection and its co-morbidities, including innate
      and adaptive immune responses. At the same time, exocrine function may also be
      influenced by pharmacotherapies directed at the infectious agents. Here, we
      briefly review the role of the salivary glands and lacrimal glands in normal
      physiology and exocrine pathogenesis within the context of HIV infection and
      acquired immune deficiency syndrome (AIDS), including the contribution of
      antiretroviral therapies on both. Subsequently, we discuss the impact of HIV
      infection and the types of antiretroviral therapy on disease management and
      therapy development efforts.

PMID- 30217036
TI  - Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain
      Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis.
AB  - The cellular cytoskeleton is central for key cellular functions, and as such is a
      marker for diseased and infected cell states. Here we analyzed infection with
      rubella virus (RV) strains with respect to phenotypes in cellular mechanical
      properties, cell movement, and viral cytopathogenicity. Real-time deformability
      cytometry (RT-DC), as a high-throughput platform for the assessment of cell
      mechanics, revealed a correlation of an increase in cortical filamentous-actin (F
      actin) with a higher cellular stiffness. The additional reduction of stress
      fibers noted for only some RV strains as the most severe actin rearrangement
      lowered cell stiffness. Furthermore, a reduced collective and single cell
      migration speed in a wound healing assay was detected in addition to severe
      changes in cell morphology. The latter was followed by activation of caspase 3/7
      as a sign for induction of apoptosis. Our study emphasizes RT-DC technology as a
      sensitive means to characterize viral cell populations and to implicate
      alterations of cell mechanical properties with cell functions. These
      interdependent events are not only promising options to elucidate viral spread
      and to understand viral pathologies within the infected host. They also
      contribute to any diseased cell state, as exemplified by RV as a representative
      agent for cytoskeletal alterations involved in a cytopathological outcome.

PMID- 30217037
TI  - Astaxanthin Prevents Alcoholic Fatty Liver Disease by Modulating Mouse Gut
      Microbiota.
AB  - The development and progression of alcoholic fatty liver disease (AFLD) is
      influenced by the intestinal microbiota. Astaxanthin, a type of oxygenated
      carotenoid with strong antioxidant and anti-inflammatory properties, has been
      proven to relieve liver injury. However, the relationship between the gut
      microbiota regulation effect of astaxanthin and AFLD improvement remains unclear.
      The effects of astaxanthin on the AFLD phenotype, overall structure, and
      composition of gut microbiota were assessed in ethanol-fed C57BL/6J mice. The
      results showed that astaxanthin treatment significantly relieves inflammation and
      decreases excessive lipid accumulation and serum markers of liver injury.
      Furthermore, astaxanthin was shown to significantly decrease species from the
      phyla Bacteroidetes and Proteobacteria and the genera Butyricimonas, Bilophila,
      and Parabacteroides, as well as increase species from Verrucomicrobia and
      Akkermansia compared with the Et (ethanol)group. Thirteen phylotypes related to
      inflammation as well as correlated with metabolic parameters were significantly
      altered by ethanol, and then notably reversed by astaxanthin. Additionally,
      astaxanthin altered 18 and 128 KEGG (Kyoto Encyclopedia of Genes and Genomes)
      pathways involved in lipid metabolism and xenobiotic biodegradation and
      metabolism at levels 2 and 3, respectively. These findings suggest that
      Aakkermansia may be a potential target for the astaxanthin-induced alleviation of
      AFLD and may be a potential treatment for bacterial disorders induced by AFLD.

PMID- 30217038
TI  - Iterative Blind Deconvolution Algorithm for Deblurring a Single PSP/TSP Image of
      Rotating Surfaces.
AB  - Imaging of pressure-sensitive paint (PSP) for pressure measurement on moving
      surfaces is problematic due to the movement of the object within the finite
      exposure time of the imager, resulting in the blurring of the blade edges. The
      blurring problem is particularly challenging when high-sensitivity PSP with a
      long lifetime is used, where the long luminescence time constant of exponential
      light decay following a burst of excitation light energy results in blurred
      images. One method to ameliorate this effect is image deconvolution using a point
      spread function (PSF) based on an estimation of the luminescent time constant.
      Prior implementations of image deconvolution for PSP deblurring have relied upon
      a spatially invariant time constant in order to reduce computational time.
      However, the use of an assumed value of time constant leads to errors in the
      point spread function, particularly when strong pressure gradients (which cause
      strong spatial gradients in the decay time constant) are involved. This work
      introduces an iterative method of image deconvolution, where a spatially variant
      PSF is used. The point-by-point PSF values are found in an iterative manner,
      since the time constant depends on the local pressure value, which can only be
      found from the reduced PSP data. The scheme estimates a super-resolved spatially
      varying blur kernel with sub-pixel resolution without filtering the blurred
      image, and then restores the image using classical iterative regularization
      tools. A kernel-free forward model has been used to generate test images with
      known pressure surface maps and a varying amount of noise to evaluate the
      applicability of this scheme in different experimental conditions. A spinning
      disk setup with a grazing nitrogen jet for producing strong pressure gradients
      has also been used to evaluate the scheme on a real-world problem. Results
      including the convergence history and the effect of a regularization-iteration
      count are shown, along with a comparison with the previous PSP deblurring method.

PMID- 30217039
TI  - Exploring Social Desirability Bias in Perceptions of Dog Adoption: All's Well
      that Ends Well? Or Does the Method of Adoption Matter?
AB  - Dogs are a popular companion animal in the United States; however, dog
      acquisition is often a contentious subject. Adoption is often cited as an ethical
      and popular method of acquisition but interpretation of the term 'adoption' may
      vary. In a nationally representative survey of the U.S., 767 respondents were
      asked questions regarding their opinions of dog acquisition and adoption. Within
      the sample, 45% had a dog; of those, 40% had adopted a dog, and 47% visited a
      veterinarian once a year. A best-worst choice experiment, where respondents were
      asked to choose the most ethical and least ethical method of acquiring a dog from
      a statistically determined set of choices, was used to elicit respondents'
      preferences for the most ethical method of dog adoption. A random parameters
      logit and a latent class model were used to estimate relative rankings of dog
      adoption methods. In the random parameters logit model, the largest preference
      share was for adoption from a municipal animal shelter (56%) and the smallest
      preference share was for adoption from a pet store (3%). Dog acquisition was
      further evaluated by creating an index of social desirability bias using how
      important respondents believed certain dog characteristics were compared to how
      important respondents believed others would rate/rank the same dog
      characteristics. The highest incidences of social desirability bias occurred for
      the dog characteristics of appearance and breed.

PMID- 30217040
TI  - The Natural Large Genomic Deletion Is Unrelated to the Increased Virulence of the
      Novel Genotype Fowl Adenovirus 4 Recently Emerged in China.
AB  - Since 2015, severe hydropericardium-hepatitis syndrome (HHS), caused by a highly
      pathogenic fowl adenovirus 4 (FAdV-4), emerged in China. In our previous study,
      the FAdV-4 has been identified as a novel genotype with a unique 1966-bp
      nucleotide deletion (1966Del) between open reading frame 42 and 43. In this
      study, the natural 1966Del was frequently identified among 17 clinical isolates
      and other reported Chinese clinical strains. To investigate the relationship
      between 1966Del and the increased virulence of the novel FAdV-4, a CRISPR/Cas9
      operating platform for FAdV-4 was developed for the first time in this study.
      Based on this platform, a Re1966 strain was rescued, inserted the relative
      1966Del sequence of a nonpathogenic strain KR5. In the pathogenicity study, the
      Re1966 strain retained high virulence for specific-pathogen-free chickens,
      similar to the parental wild-type HLJFAd15, although the survival time of
      chickens infected with Re1966 was much longer. Therefore, the natural 1966Del was
      identified as a non-essential site for the increased virulence of the emerged
      novel FAdV-4. Although further research on the virulence-determining region or
      point within the genome of the novel FAdV-4 is needed, the CRISPR/Cas9 operating
      platform for the novel FAdV-4 was developed and successfully applied to edit the
      genomic DNA for the first time, and it provides a novel powerful tool for both
      basic virology studies and vaccine vector development of FAdVs.

PMID- 30217042
TI  - Lead Poisoning and the Dangers of Pragmatism.
AB  - Drawing from ethnographic research on lead poisoning in Uruguay and secondary
      literature from lead poisoning cases around the world, the commentary argues that
      public health policy guided by pragmatism presents multiple dangers to effective
      health intervention.

PMID- 30217041
TI  - The Diagnosis and Clinical Significance of Paragangliomas in Unusual Locations.
AB  - Paragangliomas are neuroendocrine neoplasms, derived from paraganglia of the
      sympathetic and parasympathetic nervous systems. They are most commonly
      identified in the head and neck, being most frequent in the carotid body,
      followed by jugulotympanic paraganglia, vagal nerve and ganglion nodosum, as well
      as laryngeal paraganglia. Abdominal sites include the well-known urinary bladder
      tumors that originate in the Organ of Zuckerkandl. However, other unusual sites
      of origin include peri-adrenal, para-aortic, inter-aortocaval, and paracaval
      retroperitoneal sites, as well as tumors in organs where they may not be expected
      in the differential diagnosis of neuroendocrine neoplasms, such as thyroid,
      parathyroid, pituitary, gut, pancreas, liver, mesentery, lung, heart and
      mediastinum. The distinction of these lesions from epithelial neuroendocrine
      neoplasms is critical for several reasons. Firstly, the determination of clinical
      and biochemical features is different from that used for epithelial
      neuroendocrine tumors. Secondly, the genetic implications are different, since
      paragangliomas/pheochromocytomas have the highest rate of germline susceptibility
      at almost 40%. Finally, the characterization of metastatic disease is unique in
      these highly syndromic lesions. In this review, we summarize updated concepts by
      outlining the spectrum of anatomic locations of paragangliomas, the importance of
      morphology in establishing the correct diagnosis, the clinical implications for
      management, and the impact of genetics on the distinction between multifocal
      primary tumors compared with malignant disease.

PMID- 30217043
TI  - Determinants of Health Care-Seeking Delay among Tuberculosis Patients in Rural
      Area of Central China.
AB  - Background The prevalence of tuberculosis (TB) in low and middle-income countries
      is a significant public health and social concern. TB is a common infectious
      disease caused by the Mycobacterium tuberculosis infection, which has a
      widespread infection rate. Health care-seeking delay maybe one of the most
      important neglected risk factors for the spread of TB. Objectives The aim of this
      study was to understand the situation of health care-seeking delay among rural
      tuberculosis patients in Hubei Province, and explore its risk factors. Methods A
      total of 1408 rural tuberculosis patients were surveyed using a standard
      structured questionnaire in three cities of Hubei Province during the past two
      years. Results For the 1408cases of pulmonary tuberculosis, 39.70% of them were
      health care-seeking delayed. Logistic regressions indicate that the Han
      nationality, farming careers, the over 45 min walk to the township's hospital,
      and awareness of the national TB free treatment policy, were significantly
      associated with higher odds of a delay in care seeking. Conclusions The
      prevalence of health care-seeking delay among tuberculosis patients was high in
      rural areas. It is essential to take comprehensive targeted interventions to
      reduce care-seeking delay.

PMID- 30217044
TI  - Water Level Reconstruction and Prediction Based on Space-Borne Sensors: A Case
      Study in the Mekong and Yangtze River Basins.
AB  - Water level (WL) measurements denote surface conditions that are useful for
      monitoring hydrological extremes, such as droughts and floods, which both affect
      agricultural productivity and regional development. Due to spatially sparse in
      situ hydrological stations, remote sensing measurements that capture localized
      instantaneous responses have recently been demonstrated to be a viable
      alternative to WL monitoring. Despite a relatively good correlation with WL, a
      traditional passive remote sensing derived WL is reconstructed from nearby
      remotely sensed surface conditions that do not consider the remotely sensed
      hydrological variables of a whole river basin. This method's accuracy is also
      limited. Therefore, a method based on basin-averaged, remotely sensed
      precipitation from the Tropical Rainfall Measuring Mission (TRMM) and
      gravimetrically derived terrestrial water storage (TWS) from the Gravity Recovery
      and Climate Experiment (GRACE) is proposed for WL reconstruction in the Yangtze
      and Mekong River basins in this study. This study examines the WL reconstruction
      performance from these two remotely sensed hydrological variables and their
      corresponding drought indices (i.e., TRMM Standardized Precipitation Index (TRMM
      SPI) and GRACE Drought Severity Index (GRACE-DSI)) on a monthly temporal scale. A
      weighting procedure is also developed to explore a further potential improvement
      in the WL reconstruction. We found that the reconstructed WL derived from the
      hydrological variables compares well to the observed WL. The derived drought
      indices perform even better than those of their corresponding hydrological
      variables. The indices' performance rate is owed to their ability to bypass the
      influence of El Nino Southern Oscillation (ENSO) events in a standardized form
      and their basin-wide integrated information. In general, all performance
      indicators (i.e., the Pearson Correlation Coefficient (PCC), Root-mean-squares
      error (RMSE), and Nash-Sutcliffe model efficiency coefficient (NSE)) reveal that
      the remotely sensed hydrological variables (and their corresponding drought
      indices) are better alternatives compared with traditional remote sensing indices
      (e.g., Normalized Difference Vegetation Index (NDVI)), despite different
      geographical regions. In addition, almost all results are substantially improved
      by the weighted averaging procedure. The most accurate WL reconstruction is
      derived from a weighted TRMM-SPI for the Mekong (and Yangtze River basins) and
      displays a PCC of 0.98 (and 0.95), a RMSE of 0.19 m (and 0.85 m), and a NSE of
      0.95 (and 0.89); by comparison, the remote sensing variables showed less accurate
      results (PCC of 0.88 (and 0.82), RMSE of 0.41 m (and 1.48 m), and NSE of 0.78
      (and 0.67)) for its inferred WL. Additionally, regardless of weighting, GRACE-DSI
      displays a comparable performance. An external assessment also shows similar
      results. This finding indicates that the combined usage of remotely sensed
      hydrological variables in a standardized form and the weighted averaging
      procedure could lead to an improvement in WL reconstructions for river basins
      affected by ENSO events and hydrological extremes.

PMID- 30217045
TI  - Porous Calcium Phosphate Ceramic Scaffolds with Tailored Pore Orientations and
      Mechanical Properties Using Lithography-Based Ceramic 3D Printing Technique.
AB  - This study demonstrates the usefulness of the lithography-based ceramic 3
      dimensional printing technique with a specifically designed top-down process for
      the production of porous calcium phosphate (CaP) ceramic scaffolds with tailored
      pore orientations and mechanical properties. The processing parameters including
      the preparation of a photocurable CaP slurry with a high solid loading (phi = 45
      vol%), the exposure time for photocuring process, and the initial designs of the
      porous scaffolds were carefully controlled. Three types of porous CaP scaffolds
      with different pore orientations (i.e., 0 degrees /90 degrees , 0 degrees /45
      degrees /90 degrees /135 degrees , and 0 degrees /30 degrees /60 degrees /90
      degrees /120 degrees /150 degrees ) were produced. All the scaffolds exhibited a
      tightly controlled porous structure with straight CaP frameworks arranged in a
      periodic pattern while the porosity was kept constant. The porous CaP scaffold
      with a pore orientation of 0 degrees /90 degrees  demonstrated the highest
      compressive strength and modulus due to a number of CaP frameworks parallel to
      the loading direction. On the other hand, scaffolds with multiple pore
      orientations may exhibit more isotropic mechanical properties regardless of the
      loading directions. The porous CaP scaffolds exhibited an excellent in vitro
      apatite-forming ability in a stimulated body fluid (SBF) solution. These findings
      suggest that porous CaP scaffolds with tailored pore orientations may provide
      tunable mechanical properties with good bone regeneration ability.

PMID- 30217046
TI  - Enhanced Photodynamic Anticancer Activities of Multifunctional Magnetic
      Nanoparticles (Fe3O4) Conjugated with Chlorin e6 and Folic Acid in Prostate and
      Breast Cancer Cells.
AB  - Photodynamic therapy (PDT) is a promising alternative to conventional cancer
      treatment methods. Nonetheless, improvement of in vivo light penetration and
      cancer cell-targeting efficiency remain major challenges in clinical photodynamic
      therapy. This study aimed to develop multifunctional magnetic nanoparticles
      conjugated with a photosensitizer (PS) and cancer-targeting molecules via a
      simple surface modification process for PDT. To selectively target cancer cells
      and PDT functionality, core magnetic (Fe3O4) nanoparticles were covalently bound
      with chlorin e6 (Ce6) as a PS and folic acid (FA). When irradiated with a 660-nm
      long-wavelength light source, the Fe3O4-Ce6-FA nanoparticles with good
      biocompatibility exerted marked anticancer effects via apoptosis, as confirmed by
      analyzing the translocation of the plasma membrane, nuclear fragmentation,
      activities of caspase-3/7 in prostate (PC-3) and breast (MCF-7) cancer cells.
      Ce6, used herein as a PS, is thus more useful for PDT because of its ability to
      produce a high singlet oxygen quantum yield, which is owed to deep penetration by
      virtue of its long-wavelength absorption band; however, further in vivo studies
      are required to verify its biological effects for clinical applications.

PMID- 30217047
TI  - Impact of Two-Dimensional Particle Size Distribution on Estimation of Water Vapor
      Diffusivity in Micrometric Size Cellulose Particles.
AB  - This work aims at assessing the impact of two-dimensional particle size
      distribution (2D-PSD) on the identification of water vapor diffusivity in
      micrometric size cellulose particles displaying a size aspect ratio lower than 2
      and a cylindrical shape. First, different methodologies to obtain the two
      dimensional (2D) particle size distribution (diameter versus length) were
      compared, based on image analysis. Then, experimental sorption kinetics were
      obtained by using a quartz crystal microbalance (QCM) coupled with a water vapor
      adsorption system. Diffusivity values were estimated when considering either the
      2D-PSD or global descriptors, such as the mean or median diameter and length of
      particles. Results revealed that the use of an analytical approach when
      considering the 2D mean-PSD or the median-PSD was the most accurate way to get
      diffusivity values at the scale of particles in a polydisperse sample of
      cellulose particles. Following this approach, a water vapor apparent diffusivity
      of 3.1 * 10-12 +/- 2.3 * 10-12 m2.s-1 was found for the considered cellulose
      sample. Neglecting PSD in diffusivity estimation led to an underestimation of a
      factor of 2. This procedure could be extended for all the polydisperse samples in
      order to have an accurate estimation of water vapor diffusivity at the scale of
      single particles.

PMID- 30217048
TI  - Aerobic Physical Activity and a Low Glycemic Diet Reduce the AA/EPA Ratio in Red
      Blood Cell Membranes of Patients with NAFLD.
AB  - Omega-6 Polyunsaturated Fatty Acids (PUFAs), through the eicosanoids derived from
      arachidonic acid (AA), are able to modulate the inflammatory processes, whereas
      omega-3 PUFAs, such as eicosapentaenoic acid (EPA), exert anti-oxidant and anti
      inflammatory effects. An unbalanced AA/EPA ratio in favor of AA leads to the
      development of different metabolic disorders, including non-alcoholic fatty liver
      disease (NAFLD). The aim of the present study was to evaluate the effects of
      different diets, alone and in combination with two physical activity programs, on
      the AA/EPA ratio value in erythrocyte membranes of patients with NAFLD. One
      hundred forty-two subjects with NAFLD were enrolled in the study and randomized
      into six treatment groups. AA/EPA ratio was significantly reduced after 90 days
      of treatment with only a program of aerobic activity. However, it appears that
      the combination of physical activity and a Low Glycemic Index Mediterranean Diet
      (LGIMD) was more efficacious in reducing AA/EPA levels, at 45 days of treatment,
      even if this effect was not maintained over time. The combined effect of diet and
      physical activity reduced the AA/EPA ratio value improving the score of
      steatosis. Dietary intake of omega-3 PUFAs, in association with a healthy
      lifestyle, may be used in the prevention protocols for many chronic diseases,
      including NAFLD.

PMID- 30217049
TI  - HEAR: Approach for Heartbeat Monitoring with Body Movement Compensation by IR-UWB
      Radar.
AB  - Further applications of impulse radio ultra-wideband radar in mobile health are
      hindered by the difficulty in extracting such vital signals as heartbeats from
      moving targets. Although the empirical mode decomposition based method is applied
      in recovering waveforms of heartbeats and estimating heart rates, the
      instantaneous heart rate is not achievable. This paper proposes a Heartbeat
      Estimation And Recovery (HEAR) approach to expand the application to mobile
      scenarios and extract instantaneous heartbeats. Firstly, the HEAR approach
      acquires vital signals by mapping maximum echo amplitudes to the fast time delay
      and compensating large body movements. Secondly, HEAR adopts the variational
      nonlinear chirp mode decomposition in extracting instantaneous frequencies of
      heartbeats. Thirdly, HEAR extends the clutter removal method based on the wavelet
      decomposition with a two-parameter exponential threshold. Compared to heart rates
      simultaneously collected by electrocardiograms (ECG), HEAR achieves a minimum
      error rate 4.6% in moving state and 2.25% in resting state. The Bland-Altman
      analysis verifies the consistency of beat-to-beat intervals in ECG and extracted
      heartbeat signals with the mean deviation smaller than 0.1 s. It indicates that
      HEAR is practical in offering clinical diagnoses such as the heart rate
      variability analysis in mobile monitoring.

PMID- 30217050
TI  - TPS Genes Silencing Alters Constitutive Indirect and Direct Defense in Tomato.
AB  - Following herbivore attacks, plants modify a blend of volatiles organic compounds
      (VOCs) released, resulting in the attraction of their antagonists. However,
      volatiles released constitutively may affect herbivores and natural enemies'
      fitness too. In tomato there is still a lack of information on the genetic bases
      responsible for the constitutive release of VOC involved in direct and indirect
      defenses. Here we studied the constitutive emissions related to the two most
      abundant sesquiterpene synthase genes expressed in tomato and their functional
      role in plant defense. Using an RNA interference approach, we silenced the
      expression of TPS9 and TPS12 genes and assessed the effect of this transformation
      on herbivores and parasitoids. We found that silenced plants displayed a
      different constitutive volatiles emission from controls, resulting in reduced
      attractiveness for the aphid parasitoid Aphidius ervi and in an impaired
      development of Spodoptera exigua larvae. We discussed these data considering the
      transcriptional regulation of key-genes involved in the pathway of VOC
      metabolism. We provide several lines of evidence on the metabolic flux from
      terpenoids to phenylpropanoids. Our results shed more light on constitutive
      defenses mediated by plant volatiles and on the molecular mechanisms involved in
      their metabolic regulation.

PMID- 30217051
TI  - Whole Body Vibration Therapy after Ischemia Reduces Brain Damage in
      Reproductively Senescent Female Rats.
AB  - A risk of ischemic stroke increases exponentially after menopause. Even a mild
      ischemic stroke can result in increased frailty. Frailty is a state of increased
      vulnerability to adverse outcomes, which subsequently increases risk of
      cerebrovascular events and severe cognitive decline, particularly after
      menopause. Several interventions to reduce frailty and subsequent risk of stroke
      and cognitive decline have been proposed in laboratory animals and patients. One
      of them is whole body vibration (WBV). WBV improves cerebral function and
      cognitive ability that deteriorates with increased frailty. The goal of the
      current study is to test the efficacy of WBV in reducing post-ischemic stroke
      frailty and brain damage in reproductively senescent female rats. Reproductively
      senescent Sprague-Dawley female rats were exposed to transient middle cerebral
      artery occlusion (tMCAO) and were randomly assigned to either WBV or no-WBV
      groups. Animals placed in the WBV group underwent 30 days of WBV (40 Hz)
      treatment performed twice daily for 15 min each session, 5 days each week. The
      motor functions of animals belonging to both groups were tested intermittently
      and at the end of the treatment period. Brains were then harvested for
      inflammatory markers and histopathological analysis. The results demonstrate a
      significant reduction in inflammatory markers and infarct volume with significant
      increases in brain-derived neurotrophic factor and improvement in functional
      activity after tMCAO in middle-aged female rats that were treated with WBV as
      compared to the no-WBV group. Our results may facilitate a faster translation of
      the WBV intervention for improved outcome after stroke, particularly among frail
      women.

PMID- 30217052
TI  - Investigating Metal-Insulator Transition and Structural Phase Transformation in
      the (010)-VO2/(001)-YSZ Epitaxial Thin Films.
AB  - The VO2 thin films with sharp metal-insulator transition (MIT) were epitaxially
      grown on (001)-oriented Yttria-stabilized zirconia substrates (YSZ) using radio
      frequency (RF) magnetron sputtering techniques. The MIT and structural phase
      transition (SPT) were comprehensively investigated under in situ temperature
      conditions. The amplitude of MIT is in the order of magnitude of 104, and
      critical temperature is 342 K during the heating cycle. It is interesting that
      both electron concentration and mobility are changed by two orders of magnitude
      across the MIT. This research is distinctively different from previous studies,
      which found that the electron concentration solely contributes to the amplitude
      of the MIT, although the electron mobility does not. Analysis of the SPT showed
      that the (010)-VO2/(001)-YSZ epitaxial thin film presents a special multi-domain
      structure, which is probably due to the symmetry matching and lattice mismatch
      between the VO2 and YSZ substrate. The VO2 film experiences the SPT from the M1
      phase at low temperature to a rutile phase at a high temperature. Moreover, the
      SPT occurs at the same critical temperature as that of the MIT. This work may
      shed light on a new MIT behavior and may potentially pave the way for preparing
      high-quality VO2 thin films on cost-effective YSZ substrates for photoelectronic
      applications.

PMID- 30217054
TI  - Automatic Spot Identification Method for High Throughput Surface Plasmon
      Resonance Imaging Analysis.
AB  - An automatic spot identification method is developed for high throughput surface
      plasmon resonance imaging (SPRi) analysis. As a combination of video accessing,
      image enhancement, image processing and parallel processing techniques, the
      method can identify the spots in SPRi images of the microarray from SPRi video
      data. In demonstrations of the method, SPRi video data of different protein
      microarrays were processed by the method. Results show that our method can locate
      spots in the microarray accurately regardless of the microarray pattern, spot
      background contrast, light nonuniformity and spotting defects, but also can
      provide address information of the spots.

PMID- 30217053
TI  - Natural Peptides in Drug Discovery Targeting Acetylcholinesterase.
AB  - Acetylcholinesterase-inhibitory peptide has gained much importance since it can
      inhibit acetylcholinesterase (AChE) and increase the availability of
      acetylcholine in cholinergic synapses, enhancing cholinergic transmission in
      pharmacological treatment of Alzheimer's disease (AD). Natural peptides have
      received considerable attention as biologically important substances as a source
      of AChE inhibitors. These natural peptides have high potential pharmaceutical and
      medicinal values due to their bioactivities as neuroprotective and
      neurodegenerative treatment activities. These peptides have attracted great
      interest in the pharmaceutical industries, in order to design potential peptides
      for use in the prophylactic and therapy purposes. Some natural peptides and their
      derivatives have high commercial values and have succeeded in reaching the
      pharmaceutical market. A large number of peptides are already in preclinical and
      clinical pipelines for treatment of various diseases. This review highlights the
      recent researches on the various natural peptides and future prospects for AD
      management.

PMID- 30217055
TI  - Development and Experimental Evaluation of a 3D Vision System for Grinding Robot.
AB  - If the grinding robot can automatically position and measure the machining target
      on the workpiece, it will significantly improve its machining efficiency and
      intelligence level. However, unfortunately, the current grinding robot cannot do
      this because of economic and precision reasons. This paper proposes a 3D vision
      system mounted on the robot's fourth joint, which is used to detect the machining
      target of the grinding robot. Also, the hardware architecture and data processing
      method of the 3D vision system is described in detail. In the data processing
      process, we first use the voxel grid filter to preprocess the point cloud and
      obtain the feature descriptor. Then use fast library for approximate nearest
      neighbors (FLANN) to search out the difference point cloud from the precisely
      registered point cloud pair and use the point cloud segmentation method proposed
      in this paper to extract machining path points. Finally, the detection error
      compensation model is used to accurately calibrate the 3D vision system to
      transform the machining information into the grinding robot base frame.
      Experimental results show that the absolute average error of repeated
      measurements at different locations is 0.154 mm, and the absolute measurement
      error of the vision system caused by compound error is usually less than 0.25 mm.
      The proposed 3D vision system could easily integrate into an intelligent grinding
      system and may be suitable for industrial sites.

PMID- 30217056
TI  - Spotted Wing Drosophila in Sweet Cherry Orchards in Relation to Forest
      Characteristics, Bycatch, and Resource Availability.
AB  - Forest vegetation is essential for the population development of the spotted wing
      drosophila (SWD). Yet, little is known of how the structure of surrounding forest
      areas influence the abundance of SWD within orchards. In this work, we use data
      from a field trial at five sites in Switzerland to analyse the relationship
      between the extent of forest area, its edge density, and its distance from the
      orchard with the occurrence of SWD in sweet cherry orchards in a Bayesian
      hierarchical model. Availability of cherries and bycatch were also included in
      the model to account for effects of resource availability and trap
      attractiveness, respectively. For all main effects and their interactions, we
      accounted for potential temporal changes by adding interactions with time. We
      found that the closer an orchard was to a forest, the more SWD were trapped
      within the orchard. However, the interaction of forest proximity with forest area
      caused a disproportionate decrease of SWD catches. Also, the within orchard
      variables, trap catches of other drosophilid flies and resource availability
      affected SWD trap catches, but their relation changed in the course of the
      experiment. The findings imply that reducing SWD occurrence in orchards and other
      crop fields requires not only the consideration of processes outside and within
      the host crop field, but also of temporally changing relationships between SWD
      and other factors.

PMID- 30217057
TI  - Proteomic Deep Mining the Venom of the Red-Headed Krait, Bungarus flaviceps.
AB  - The use of -omics technologies allows for the characterization of snake venom
      composition at a fast rate and at high levels of detail. In the present study, we
      investigated the protein content of Red-headed Krait (Bungarus flaviceps) venom.
      This analysis revealed a high diversity of snake venom protein families, as
      evidenced by high-throughput mass spectrometric analysis. We found all six venom
      protein families previously reported in a transcriptome study of the venom gland
      of B. flaviceps, including phospholipases A2 (PLA2s), Kunitz-type serine
      proteinase inhibitors (KSPIs), three-finger toxins (3FTxs), cysteine-rich
      secretory proteins (CRISPs), snaclecs, and natriuretic peptides. A combined
      approach of automated database searches and de novo sequencing of tandem mass
      spectra, followed by sequence similarity searches, revealed the presence of 12
      additional toxin families. De novo sequencing alone was able to identify 58
      additional peptides, and this approach contributed significantly to the
      comprehensive description of the venom. Abundant protein families comprise 3FTxs
      (22.3%), KSPIs (19%), acetylcholinesterases (12.6%), PLA2s (11.9%), venom
      endothelial growth factors (VEGFs, 8.4%), nucleotidases (4.3%), and C-type lectin
      like proteins (snaclecs, 3.3%); an additional 11 toxin families are present at
      significantly lower concentrations, including complement depleting factors, a
      family not previously detected in Bungarus venoms. The utility of a multifaceted
      approach toward unraveling the proteome of snake venoms, employed here, allowed
      detection of even minor venom components. This more in-depth knowledge of the
      composition of B. flaviceps venom facilitates a better understanding of snake
      venom molecular evolution, in turn contributing to more effective treatment of
      krait bites.

PMID- 30217058
TI  - Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in
      Pancreatic Ductal Adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive carcinoma
      entities worldwide with early and rapid dissemination. Recently, we discussed the
      role of microRNAs as epigenetic regulators of Epithelial-to-Mesenchymal
      Transition (EMT) in PDAC. In this study, we investigated their value as
      diagnostic and prognostic markers in tissue and blood samples of 185 patients
      including PDAC, non-malignant pancreatic disorders, and age-matched healthy
      controls. Expression of the microRNA-200-family (microRNAs -141, -200a, -200b, 
      200c, -429) and microRNA-148a was significantly downregulated in tissue of PDAC
      Union internationale contre le cancer (UICC) Stage II. Correspondingly, stromal
      PDAC tissue showed strong expression of Fibronectin, Vimentin, and ZEB-1 (Zinc
      finger E-box-binding homeobox) versus low expression of E-cadherin. Transient
      transfection of microRNA-200b and microRNA-200c mimics resulted in the
      downregulation of their key target ZEB-1. Inversely, blood serum analyses of
      patients with PDAC UICC Stages II, III, and IV showed a significant over
      expression of microRNA-200-family members, microRNA-148a, microRNA-10b, and
      microRNA-34a. Correspondingly, Enzyme-linked Immunosorbent Assay (ELISA) analyses
      revealed a significant over-expression of soluble E-cadherin in serum samples of
      PDAC patients versus healthy controls. The best diagnostic accuracy to
      distinguish between PDAC and non-PDAC in this patient collective could be
      achieved in tissue by microRNA-148a with an area under the receiver-operating
      characteristic (ROC) curve (AUC) of 0.885 and in blood serum by a panel of
      microRNA-141, -200b, -200c, and CA.19-9 with an AUC of 0.890. Both diagnostic
      tools outreach the diagnostic performance of the currently most common diagnostic
      biomarker CA.19-9 (AUC of 0.834). Kaplan Meier survival analysis of this patient
      collective revealed an improved overall survival in PDAC patients with high
      expression of tissue-related microRNA-34a, -141, -200b, -200c, and -429. In
      conclusion, EMT-regulating microRNAs have great potential as liquid and solid
      biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain
      important tasks for future studies.

PMID- 30217059
TI  - Comparative Study of Square and Circular Loop Frequency Selective Surfaces for
      Millimeter-Wave Imaging Diagnostics Systems.
AB  - A design method of large-sized square-loop and circular-loop frequency selective
      surface (FSS) filters for protection of mm-wave imagining receivers is presented.
      Due to fine cell structure requirements, the performance of the FSS structures at
      mm-wave frequencies can be significantly affected by fabrication tolerances,
      especially involved with large-size panel fabrication. Through a comprehensive
      parametric variation study on the performance of square-loop and circular-loop
      FSS structures, it is found that the circular-loop FSS structure performs much
      less sensitively to the fabrication tolerances, thereby producing better and
      consistent performances with given design values. As a design example, square
      loop and circular-loop notch filters resonating at 105 GHz were designed and the
      performances were evaluated with multiple prototypes. The resonant frequencies of
      the implemented circular-loop FSS filters deviated by only about 0.5 GHz from the
      accurate designed value, which can be easily adjusted in the design process. The
      implemented square-loop and circular loop FSS filters provided low-loss in the
      pass-band and high rejection of 23 dB at the resonant frequency with good oblique
      angle performance.

PMID- 30217060
TI  - A Bayesian Downscaler Model to Estimate Daily PM2.5 Levels in the Conterminous
      US.
AB  - There has been growing interest in extending the coverage of ground particulate
      matter with aerodynamic diameter <= 2.5 MUm (PM2.5) monitoring networks based on
      satellite remote sensing data. With broad spatial and temporal coverage, a
      satellite-based monitoring network has a strong potential to complement the
      ground monitor system in terms of the spatiotemporal availability of the air
      quality data. However, most existing calibration models focus on a relatively
      small spatial domain and cannot be generalized to a national study. In this
      paper, we proposed a statistically reliable and interpretable national modeling
      framework based on Bayesian downscaling methods to be applied to the calibration
      of the daily ground PM2.5 concentrations across the conterminous United States
      using satellite-retrieved aerosol optical depth (AOD) and other ancillary
      predictors in 2011. Our approach flexibly models the PM2.5 versus AOD and the
      potential related geographical factors varying across the climate regions and
      yields spatial- and temporal-specific parameters to enhance model
      interpretability. Moreover, our model accurately predicted the national PM2.5
      with an R2 at 70% and generated reliable annual and seasonal PM2.5 concentration
      maps with its SD. Overall, this modeling framework can be applied to national
      scale PM2.5 exposure assessments and can also quantify the prediction errors.

PMID- 30217061
TI  - Postprandial Hypertriglyceridemia Is Associated with the Variant 54 Threonine
      FABP2 Gene.
AB  - Purpose: Fasting or postprandial hypertriglyceridemia is considered an
      independent cardiovascular disease (CVD) risk factor. The intestinal fatty acid
      binding protein (FABP2) is involved in the intracellular transport and metabolism
      of fatty acids. The presence of the Ala54Thr polymorphism of the FABP2 gene
      appears to be involved in postprandial hypertriglyceridemia. We explored the
      possible association of the Ala54Thr polymorphism with fat intolerance in
      apparently healthy, fasting, normolipidemic subjects with normal body-mass index
      and without diabetes. Methodology: A total of 158 apparently healthy individuals
      were classified as fat tolerant (n = 123) or intolerant (n = 35) according to
      their response (plasma triglycerides) to an oral abbreviated tolerance test with
      blood samples taken at 0, 2 and 4 h. At 0 h, all subjects ingested 26.3 g of
      fats. Presence of the Ala54Thr polymorphism of the FABP2 gene was evaluated by
      polymerase chain reaction-restriction fragment length (PCR-RFLP). Results: The
      group with fat intolerance (postprandial hypertriglyceridemia group) showed an
      increased frequency of the Thr54Thr genotype when compared with the group with
      normal fat tolerance (control group) (23% vs. 4%, respectively, OR: 16.53, 95%
      CI: 4.09-66.82, p: 0.0001, pc: 0.0003). Carriers of at least one Thr54 allele
      were up to six times more prevalent in the fat intolerant group than in the non
      carriers. (OR: 6.35; 95% CI: 1.86-21.59, p: 0.0003, pc: 0.0009). The levels of
      plasma triglycerides (Tg) at 4 h after the test meal were higher in carriers of
      at least one 54Thr allele than in carriers of the Ala54 allele (p < 0.05).
      Conclusions: There is a significant association between postprandial
      hypertriglyceridemia and the presence of at least one 54Thr allele of the FABP2
      gene. In addition, subjects with this genotype showed an increased ratio of
      Tg/HDL-cholesterol. This parameter is a marker of increased CVD risk and insulin
      resistance.

PMID- 30217062
TI  - Unobtrusive Vital Sign Monitoring in Automotive Environments-A Review.
AB  - This review provides an overview of unobtrusive monitoring techniques that could
      be used to monitor some of the human vital signs (i.e., heart activity, breathing
      activity, temperature and potentially oxygen saturation) in a car seat. It will
      be shown that many techniques actually measure mechanical displacement, either on
      the body surface and/or inside the body. However, there are also techniques like
      capacitive electrocardiogram or bioimpedance that reflect electrical activity or
      passive electrical properties or thermal properties (infrared thermography). In
      addition, photopleythysmographic methods depend on optical properties (like
      scattering and absorption) of biological tissues and-mainly-blood. As all
      unobtrusive sensing modalities are always fragile and at risk of being
      contaminated by disturbances (like motion, rapidly changing environmental
      conditions, triboelectricity), the scope of the paper includes a survey on
      redundant sensor arrangements. Finally, this review also provides an overview of
      automotive demonstrators for vital sign monitoring.

PMID- 30217063
TI  - Investigation into the Potential Migration of Nanoparticles from Laponite-Polymer
      Nanocomposites.
AB  - In this study, the migration potential of laponite, a small synthetic nanoclay,
      from nanocomposites into foods was investigated. First, a laponite/ethylene vinyl
      acetate (EVA) masterbatch was compounded several times and then extruded into
      thin low-density polyethylene (LDPE) based films. This way, intercalation and
      partial exfoliation of the smallest type of clay was achieved. Migration of
      laponite was investigated using Asymmetric Flow Field-Flow Fractionation (AF4)
      with Multi-Angle Laser Light Scattering (MALLS) detection. A surfactant solution
      in which laponite dispersion remained stable during migration test conditions was
      used as alternative food simulant. Sample films with different loadings of
      laponite were stored for 10 days at 60  degrees C. No migration of laponite was
      found at a limit of detection of 22 ug laponite per Kg food. It can be concluded
      that laponite (representing the worst case for any larger structured type of
      clay) does not migrate into food once it is incorporated into a polymer matrix.

PMID- 30217064
TI  - Bistatic ISAR Imaging with a V-FM Waveform Based on a Dual-Channel-Coupled 2D-CS
      Algorithm.
AB  - Due to the sparsity of the space distribution of point scatterers and radar echo
      data, the theory of Compressed Sensing (CS) has been successfully applied in
      Inverse Synthetic Aperture Radar (ISAR) imaging, which can recover an unknown
      sparse signal from a limited number of measurements by solving a sparsity
      constrained optimization problem. In this paper, since the V style modulation(V
      FM) signal can mitigate the ambiguity apparent in range and velocity, the dual
      channel, two-dimension, compressed-sensing (2D-CS) algorithm is proposed for
      Bistatic ISAR (Bi-ISAR) imaging, which directly deals with the 2D signal model
      for image reconstruction based on solving a nonconvex optimization problem. The
      coupled 2D super-resolution model of the target's echoes is firstly established;
      then, the 2D-SL0 algorithm is applied in each channel with different
      dictionaries, and the final image is obtained by synthesizing the two channels.
      Experiments are used to test the robustness of the Bi-ISAR imaging framework with
      the two-dimensional CS method. The results show that the framework is capable
      accurately reconstructing the Bi-ISAR image within the conditions of low SNR and
      low measured data.

PMID- 30217065
TI  - A Novel Method for Designing General Window Functions with Flexible Spectral
      Characteristics.
AB  - In the field of sensor signal processing, windows are time-/frequency-domain
      weighting functions that are widely applied to reduce the well-known Gibbs
      oscillations. Conventional methods generally control the spectral characteristics
      of windows by adjusting several of the parameters of closed-form expressions.
      Designers must make trade-offs among the mainlobe width (MW), the peak sidelobe
      level (PSL), and sometimes the sidelobe fall-off rate (SLFOR) of windows by
      carefully adjusting these parameters. Generally, not all sidelobes need to be
      suppressed in specified applications. In this paper, a novel method, i.e., the
      inverse of the shaped output using the cyclic algorithm (ISO-CA), for designing
      window functions with flexible spectral characteristics is proposed. Simulations
      are conducted to test the effectiveness, flexibility and versatility of the
      method. Some experiments based on real measured data are also presented to
      demonstrate the practicability. The results show that the window functions
      generated using the cyclic algorithm (CA) yield better performance overall than
      the windows of conventional methods, achieving a narrower MW, a lower PSL, and a
      controllable SLFOR. In addition, steerable sidelobes over specified regions can
      be acquired both easily and flexibly while maintaining the original properties of
      the initial window as much as possible.

PMID- 30217066
TI  - New Triterpenoid from Novel Triterpenoid 15-O-Glycosylation on Ganoderic Acid A
      by Intestinal Bacteria of Zebrafish.
AB  - Functional bacteria that could biotransform triterpenoids may exist in the
      diverse microflora of fish intestines. Ganoderic acid A (GAA) is a major
      triterpenoid from the medicinal fungus Ganoderma lucidum. In studying the
      microbial biotransformation of GAA, dozens of intestinal bacteria were isolated
      from the excreta of zebrafish. The bacteria's ability to catalyze GAA were
      determined using ultra-performance liquid chromatography analysis. One positive
      strain, GA A07, was selected for functional studies. GA A07 was confirmed as
      Bacillus sp., based on the DNA sequences of the 16S rRNA gene. The biotransformed
      metabolite was purified with the preparative high-performance liquid
      chromatography method and identified as GAA-15-O-beta-glucoside, based on the
      mass and nuclear magnetic resonance spectral data. The present study is the first
      to report the glycosylation of Ganoderma triterpenoids. Moreover, 15-O
      glycosylation is a new microbial biotransformation of triterpenoids, and the
      biotransformed metabolite, GAA-15-O-beta-glucoside, is a new compound.

PMID- 30217067
TI  - Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces
      Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
AB  - Although cancer cells need more glucose than normal cells to maintain energy
      demand, chronic hyperglycemia induces metabolic alteration that may dysregulate
      signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible
      factor 1-alpha) pathways. Metformin was demonstrated to evoke metabolic stress
      and induce cancer cell death. The aim of this study was to determine the
      cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and
      normoglycemia. To identify the potential mechanism, we assessed the expression of
      O-linked beta-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O
      GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose
      transporters (GLUT1, GLUT3). SKOV-3 cells were cultured in normoglycaemia (NG, 5
      mM) and hyperglycemia (HG, 25 mM) with and without 10 mM metformin for 24, 48,
      and 72 h. The proliferation rate, apoptotic and necrotic SKOV-3 cell death were
      evaluated. Real-Time qPCR was employed to determine mRNA expression of OGT, OGA,
      GLUT1, GLUT3, and HIF1A. Metformin significantly reduced the proliferation of
      SKOV-3 cells under normal glucose conditions. Whereas, the efficacy of metformin
      to induce SKOV-3 cell death was reduced in hyperglycemia. Both hyperglycemia and
      metformin induced changes in the expression of genes involved in the O
      GlcNAcylation status and HIF1A pathway. The obtained results suggest that
      dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via
      hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin
      in human ovarian cancer cells.

PMID- 30217068
TI  - Supercritical Carbon Dioxide Extraction of Astaxanthin, Lutein, and Fatty Acids
      from Haematococcus pluvialis Microalgae.
AB  - Haematococcus pluvialis microalgae in the red phase can produce significant
      amounts of astaxanthin, lutein, and fatty acids (FAs), which are valuable
      antioxidants in nutraceutics and cosmetics. Extraction of astaxanthin, lutein,
      and FAs from disrupted biomass of the H. pluvialis red phase using carbon dioxide
      (CO2) in supercritical fluid extraction (SFE) conditions was investigated using a
      bench-scale reactor in a semi-batch configuration. In particular, the effect of
      extraction time (20, 40, 60, 80, and 120 min), CO2 flow rate (3.62 and 14.48
      g/min) temperature (50, 65, and 80  degrees C), and pressure (100, 400, and 550
      bar.) was explored. The results show the maximum recovery of astaxanthin and
      lutein achieved were 98.6% and 52.3%, respectively, at 50  degrees C and 550
      bars, while the maximum recovery of FAs attained was 93.2% at 65  degrees C and
      550 bars.

PMID- 30217069
TI  - Protective Actions of Anserine Under Diabetic Conditions.
AB  - BACKGROUND/AIMS: In rodents, carnosine treatment improves diabetic nephropathy,
      whereas little is known about the role and function of anserine, the methylated
      form of carnosine. METHODS: Antioxidant activity was measured by oxygen radical
      absorbance capacity and oxygen stress response in human renal tubular cells (HK
      2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice
      (db/db), the effect of short-term anserine treatment on blood glucose,
      proteinuria and vascular permeability was measured. RESULTS: Anserine has a
      higher antioxidant capacity compared to carnosine (p < 0.001). In tubular cells
      (HK-2) stressed with 25 mM glucose or 20-100 uM hydrogen peroxide, anserine but
      not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and
      protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine
      also increased hemeoxygenase (HO-1) protein and reduced total protein
      carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein
      concentrations. Three intravenous anserine injections every 48 h in 12-week-old
      db/db mice, improved blood glucose by one fifth, vascular permeability by one
      third, and halved proteinuria (all p < 0.05). CONCLUSION: Anserine is a potent
      antioxidant and activates the intracellular Hsp70/HO-1 defense system under
      oxidative and glycative stress. Short-term anserine treatment in diabetic mice
      improves glucose homeostasis and nephropathy.

PMID- 30217070
TI  - Variability of Botulinum Toxins: Challenges and Opportunities for the Future.
AB  - Botulinum neurotoxins (BoNTs) are the most potent known toxins, and are therefore
      classified as extremely harmful biological weapons. However, BoNTs are
      therapeutic drugs that are widely used and have an increasing number of
      applications. BoNTs show a high diversity and are divided into multiple types and
      subtypes. Better understanding of the activity at the molecular and clinical
      levels of the natural BoNT variants as well as the development of BoNT-based
      chimeric molecules opens the door to novel medical applications such as silencing
      the sensory neurons at targeted areas and dermal restoration. This short review
      is focused on BoNTs' variability and the opportunities or challenges posed for
      future clinical applications.

PMID- 30217071
TI  - Ascorbic Acid in Colon Cancer: From the Basic to the Clinical Applications.
AB  - Given the safety and potential benefits of intravenous ascorbic acid (AA)
      administration in cancer patients, there is merit in further exploring this
      therapeutic concept. In this review, we discuss the potential benefits of
      intravenous AA administration on colorectal cancer and we specifically focus on
      its effect on glycolysis in mutant and wild type RAS. We perform a PubMed and
      Ovid MEDLINE search using ascorbic acid, intravenous vitamin C, KRAS mutation,
      BRAF mutation and colorectal cancer (CRC) as keywords. At the cellular level,
      colorectal cancer cells undergo a metabolic shift called the Warburg effect to
      allow for more glucose absorption and utilization of glycolysis. This shift also
      allows AA to enter which leads to a disruption in the Warburg effect and a
      shutdown of the downstream KRAS pathway in mutated KRAS colon cancer cells. At
      the clinical level, AA is associated with tumour regression in advanced disease
      and improved tolerability and side effects of standard therapy. Based on these
      findings, we conclude that further clinical trials are needed on a larger scale
      to examine the therapeutic benefits of AA in colon cancer.

PMID- 30217072
TI  - Strategies to Encapsulate the Staphylococcus aureus Bacteriophage phiIPLA-RODI.
AB  - The antimicrobial properties of bacteriophages make them suitable food
      biopreservatives. However, such applications require the development of
      strategies that ensure stability of the phage particles during food processing.
      In this study, we assess the protective effect of encapsulation of the
      Staphylococcus aureus bacteriophage phiIPLA-RODI in three kinds of nanovesicles
      (niosomes, liposomes, and transfersomes). All these systems allowed the
      successful encapsulation of phage phiIPLA-RODI with an efficiency ranged between
      62% and 98%, regardless of the concentration of components (like phospholipids
      and surfactants) used for vesicle formation. Only niosomes containing 30 mg/mL of
      surfactants exhibited a slightly lower percentage of encapsulation. Regarding
      particle size distribution, the values determined for niosomes, liposomes, and
      transfersomes were 0.82 +/- 0.09 um, 1.66 +/- 0.21 um, and 0.55 +/- 0.06 um,
      respectively. Importantly, bacteriophage infectivity was maintained during
      storage for 6 months at 4  degrees C for all three types of nanovesicles, with
      the exception of liposomes containing a low concentration of components. In
      addition, we observed that niosomes partially protected the phage particles from
      low pH. Thus, while free phiIPLA-RODI was not detectable after 60 min of
      incubation at pH 4.5, titer of phage encapsulated in niosomes decreased only 2
      log units. Overall, our results show that encapsulation represents an appropriate
      procedure to improve stability and, consequently, antimicrobial efficacy of
      phages for application in the food processing industry.

PMID- 30217073
TI  - Endothelial AMP-Activated Kinase alpha1 Phosphorylates eNOS on Thr495 and
      Decreases Endothelial NO Formation.
AB  - AMP-activated protein kinase (AMPK) is frequently reported to phosphorylate
      Ser1177 of the endothelial nitric-oxide synthase (eNOS), and therefore, is linked
      with a relaxing effect. However, previous studies failed to consistently
      demonstrate a major role for AMPK on eNOS-dependent relaxation. As AMPK also
      phosphorylates eNOS on the inhibitory Thr495 site, this study aimed to determine
      the role of AMPKalpha1 and alpha2 subunits in the regulation of NO-mediated
      vascular relaxation. Vascular reactivity to phenylephrine and acetylcholine was
      assessed in aortic and carotid artery segments from mice with global (AMPKalpha-/
      ) or endothelial-specific deletion (AMPKalphaDeltaEC) of the AMPKalpha subunits.
      In control and AMPKalpha1-depleted human umbilical vein endothelial cells, eNOS
      phosphorylation on Ser1177 and Thr495 was assessed after AMPK activation with
      thiopental or ionomycin. Global deletion of the AMPKalpha1 or alpha2 subunit in
      mice did not affect vascular reactivity. The endothelial-specific deletion of the
      AMPKalpha1 subunit attenuated phenylephrine-mediated contraction in an eNOS- and
      endothelium-dependent manner. In in vitro studies, activation of AMPK did not
      alter the phosphorylation of eNOS on Ser1177, but increased its phosphorylation
      on Thr495. Depletion of AMPKalpha1 in cultured human endothelial cells decreased
      Thr495 phosphorylation without affecting Ser1177 phosphorylation. The results of
      this study indicate that AMPKalpha1 targets the inhibitory phosphorylation Thr495
      site in the calmodulin-binding domain of eNOS to attenuate basal NO production
      and phenylephrine-induced vasoconstriction.

PMID- 30217074
TI  - Bioavailability of Tea Catechins and Its Improvement.
AB  - Many in vitro studies have shown that tea catechins had vevarious health
      beneficial effects. However, inconsistent results between in vitro and in vivo
      studies or between laboratory tests and epidemical studies are observed. Low
      bioavailability of tea catechins was an important factor leading to these
      inconsistencies. Research advances in bioavailability studies involving
      absorption and metabolic biotransformation of tea catechins were reviewed in the
      present paper. Related techniques for improving their bioavailability such as
      nanostructure-based drug delivery system, molecular modification, and co
      administration of catechins with other bioactives were also discussed.

PMID- 30217075
TI  - Facile Synthesis of beta-Lactoglobulin-Functionalized Reduced Graphene Oxide and
      Trimetallic PtAuPd Nanocomposite for Electrochemical Sensing.
AB  - The use of graphene has leapt forward the materials field and the functional
      modification of graphene has not stopped. In this work, beta-lactoglobulin (BLG)
      was used to functionalize reduced graphene oxide (RGO) based on its amphiphilic
      properties. Also, trimetallic PtAuPd nanoparticles were reduced to the surface of
      BLG-functionalized RGO and formed BLG-PtAuPd-RGO nanocomposite using facile
      synthesis. Transmission electron microscopy, energy-dispersive X-ray spectroscopy
      and Fourier transform infrared spectra were used to characterize the
      nanocomposite. Electrocatalytic analysis was evaluated through cyclic voltammetry
      and chronoamperometry methods. We developed a glucose sensor by fabricating GOD
      BLG-PtAuPd-RGO/glassy carbon (GC) electrode. It presented a remarkable
      sensitivity of 63.29 MUA mM-1 cm-2 (4.43 MUA mM-1), a wider linear range from
      0.005 to 9 mM and a lower detection limit of 0.13 MUM (S/N = 3). Additionally,
      the glucose sensor exhibited excellent testing capability in human serum samples.

PMID- 30217076
TI  - Complex Event Processing for Sensor Stream Data.
AB  - As a large amount of stream data are generated through sensors over the Internet
      of Things environment, studies on complex event processing have been conducted to
      detect information required by users or specific applications in real time. A
      complex event is made by combining primitive events through a number of
      operators. However, the existing complex event-processing methods take a long
      time because they do not consider similarity and redundancy of operators. In this
      paper, we propose a new complex event-processing method considering similar and
      redundant operations for stream data from sensors in real time. In the proposed
      method, a similar operation in common events is converted into a virtual
      operator, and redundant operations on the same events are converted into a single
      operator. The event query tree for complex event detection is reconstructed using
      the converted operators. Through this method, the cost of comparison and
      inspection of similar and redundant operations is reduced, thereby decreasing the
      overall processing cost. To prove the superior performance of the proposed
      method, its performance is evaluated in comparison with existing methods.

PMID- 30217077
TI  - Pose Estimation of Sweet Pepper through Symmetry Axis Detection.
AB  - The space pose of fruits is necessary for accurate detachment in automatic
      harvesting. This study presents a novel pose estimation method for sweet pepper
      detachment. In this method, the normal to the local plane at each point in the
      sweet-pepper point cloud was first calculated. The point cloud was separated by a
      number of candidate planes, and the scores of each plane were then separately
      calculated using the scoring strategy. The plane with the lowest score was
      selected as the symmetry plane of the point cloud. The symmetry axis could be
      finally calculated from the selected symmetry plane, and the pose of sweet pepper
      in the space was obtained using the symmetry axis. The performance of the
      proposed method was evaluated by simulated and sweet-pepper cloud dataset tests.
      In the simulated test, the average angle error between the calculated symmetry
      and real axes was approximately 6.5 degrees . In the sweet-pepper cloud dataset
      test, the average error was approximately 7.4 degrees  when the peduncle was
      removed. When the peduncle of sweet pepper was complete, the average error was
      approximately 6.9 degrees . These results suggested that the proposed method was
      suitable for pose estimation of sweet peppers and could be adjusted for use with
      other fruits and vegetables.

PMID- 30217078
TI  - Degenerate PCR Primers to Reveal the Diversity of Giant Viruses in Coastal
      Waters.
AB  - "Megaviridae" is a proposed family of giant viruses infecting unicellular
      eukaryotes. These viruses are ubiquitous in the sea and have impact on marine
      microbial community structure and dynamics through their lytic infection cycle.
      However, their diversity and biogeography have been poorly characterized due to
      the scarce detection of Megaviridae sequences in metagenomes, as well as the
      limitation of reference sequences used to design specific primers for this viral
      group. Here, we propose a set of 82 degenerated primers (referred to as
      MEGAPRIMER), targeting DNA polymerase genes (polBs) of Megaviridae. MEGAPRIMER
      was designed based on 921 Megaviridae polBs from sequenced genomes and
      metagenomes. By applying this primer set to environmental DNA meta-barcoding of a
      coastal seawater sample, we report 5595 non-singleton operational taxonomic units
      (OTUs) of Megaviridae at 97% nucleotide sequence identity. The majority of the
      OTUs were found to form diverse clades, which were phylogenetically distantly
      phylogenetically related to known viruses such as Mimivirus. The Megaviridae OTUs
      detected in this study outnumber the giant virus OTUs identified in previous
      individual studies by more than an order of magnitude. Hence, MEGAPRIMER
      represents a useful tool to study the diversity of Megaviridae at the population
      level in natural environments.

PMID- 30217080
TI  - Inequities in Childhood Vaccination Coverage in Zhejiang, Province: Evidence from
      a Decomposition Analysis on Two-Round Surveys.
AB  - Objective: The objectives of this study were to determine the degree and risk
      factors of the inequity in the childhood coverage of full primary immunization
      (FPI) in Zhejiang province. Method: We used data from two rounds of vaccination
      coverage surveys among children aged 24-35 months conducted in 2014 and 2017,
      respectively. The household income per month was used as an index of
      socioeconomic status for the inequality analysis. The concentration index (CI)
      was used to quantify the degree of inequality, and the decomposition approach was
      applied to quantify the contributions from demographic factors to inequality in
      the coverage of FPI. Results: The coverage rates of FPI were 80.6%, with a CI
      value of 0.12028 for the 2014 survey, while the coverage rates of FPI were 85.2%,
      with a CI value of 0.10129 for the 2017 survey. The results of decomposition
      analysis suggested that 68.2% and 67.1% of the socioeconomic inequality in the
      coverage of FPI could be explained by the mother's education level for the 2014
      and 2017 survey, respectively. Other risk factors including birth order, ethnic
      group, mother's age, maternal employment status, residence, immigration status,
      GDP per-capita, and the percentage of the total health spending allocated to
      public health could also explain this inequality. Conclusion: The socioeconomic
      inequity in the coverage of FPI still remained, although this gap was reduced
      between 2014 and 2017. Policy recommendations for health interventions on
      reducing the inequality in the coverage of FPI should be focused on eliminating
      poverty and women's illiteracy.

PMID- 30217081
TI  - Impact and Post-Impact Performance of Sandwich Wall Boards with GFRP Face Sheets
      and a Web-Foam Core: The Effects of Impact Location.
AB  - In recent years, load-bearing exterior sandwich wall boards have been adopted in
      civil engineering. The exterior walls of structures are often exposed to low
      velocity impacts such as stones, tools, and windborne debris, etc. The ultimate
      loading capacity, deformation, and ductility of sandwich walls are weakened by
      impact loads. In this study, the sandwich wall boards consisted of glass fiber
      reinforced plastic (GFRP) face sheets and a web-foam core. The core of wall
      boards was not the isotropic material. There was no doubt that the mechanical
      performance was seriously influenced by the impact locations. Therefore, it is
      necessary to carry out an investigation on the impact and post-impact performance
      of exterior wall boards. A comprehensive testing program was conducted to
      evaluate the effects of impact locations and impact energies on the maximum
      contact load, deflection, and contact time. Meanwhile, the compression after
      impact (CAI) performance of wall boards were also studied. The results indicated
      that the impact location significantly affects the performance of wall boards.
      Compared with an un-damaged wall board, the residual ultimate loading capacity of
      damaged wall boards reduced seriously, which were not larger than 50% of the
      designed ultimate loading capacity.

PMID- 30217079
TI  - Wearable Monitoring Devices for Biomechanical Risk Assessment at Work: Current
      Status and Future Challenges-A Systematic Review.
AB  - Background: In order to reduce the risk of work-related musculoskeletal disorders
      (WMSDs) several methods have been developed, accepted by the international
      literature and used in the workplace. The purpose of this systematic review was
      to describe recent implementations of wearable sensors for quantitative
      instrumental-based biomechanical risk assessments in prevention of WMSDs.
      Methods: Articles written until 7 May 2018 were selected from PubMed, Scopus,
      Google Scholar and Web of Science using specific keywords. Results: Instrumental
      approaches based on inertial measurement units and sEMG sensors have been used
      for direct evaluations to classify lifting tasks into low and high risk
      categories. Wearable sensors have also been used for direct instrumental
      evaluations in handling of low loads at high frequency activities by using the
      local myoelectric manifestation of muscle fatigue estimation. In the field of the
      rating of standard methods, on-body wireless sensors network-based approaches for
      real-time ergonomic assessment in industrial manufacturing have been proposed.
      Conclusions: Few studies foresee the use of wearable technologies for
      biomechanical risk assessment although the requirement to obtain increasingly
      quantitative evaluations, the recent miniaturization process and the need to
      follow a constantly evolving manual handling scenario is prompting their use.

PMID- 30217083
TI  - Photoelectrocatalytic Degradation of Paraquat by Pt Loaded TiO2 Nanotubes on Ti
      Anodes.
AB  - Nanotube structured TiO2 on Ti surface were prepared in ethylene glycol
      (Ti/TiO2NTEG) medium by anodic oxidation method with different times and then the
      plates were calcinated at different temperatures. Non-nanotube structured
      Ti/TiO2, prepared by thermal oxidation method, and nanotube structured TiO2 on Ti
      plate in hydrogen fluoride solution were also prepared for comparison. Pt loaded
      Ti/TiO2NTEG photoanodes were also prepared by cyclic voltammetry method with
      different cycles and the optimum loaded Pt amount was determined. Photoanodes
      were characterized by using X-ray Diffraction (XRD), Scanning Electron Microscopy
      Energy-Dispersive X-ray Analysis (SEM-EDX), and photocurrent methods. XRD
      analyses proved that almost all TiO2 is in anatase phase. SEM analyses show that
      nanotubes and Pt nanoparticles on nanotube surface are dispersed quite
      homogeneously. The longest nanotubes were obtained in the ethylene glycol medium
      and the nanotube length increased by increasing applied anodic oxidation time. In
      addition, a linear correlation between nanotube length and XRD peak intensity was
      found. Moreover, SEM-EDX and XRD analyses evidence that Pt nanoparticles on
      nanotube surface are metallic and in cubic structure. Photoelectrocatalytic
      degradation of paraquat was performed using the prepared photoanodes. Moreover,
      electrocatalytic and photocatalytic degradations of paraquat were also
      investigated for comparison, however lower activities were observed. These
      results evidence that the photoanodes show a significant synergy for
      photoelectrocatalytic activity.

PMID- 30217082
TI  - Microfluidic-Based Single-Cell Study: Current Status and Future Perspective.
AB  - Investigation of cell behavior under different environments and manual operations
      can give information in specific cellular processes. Among all cell-based
      analysis, single-cell study occupies a peculiar position, while it can avoid the
      interaction effect within cell groups and provide more precise information.
      Microfluidic devices have played an increasingly important role in the field of
      single-cell study owing to their advantages: high efficiency, easy operation, and
      low cost. In this review, the applications of polymer-based microfluidics on cell
      manipulation, cell treatment, and cell analysis at single-cell level are detailed
      summarized. Moreover, three mainly types of manufacturing methods, i.e.,
      replication, photodefining, and soft lithography methods for polymer-based
      microfluidics are also discussed.

PMID- 30217084
TI  - Correction: Li, X.; et al. Identification and Characterization of the WOX Family
      Genes in Five Solanaceae Species Reveal Their Conserved Roles in Peptide
      Signaling. Genes 2018, 9, 260.
AB  - The authors wish to make the following change in their paper [...].

PMID- 30217085
TI  - Integrated Longitudinal and Lateral Networked Control System Design for Vehicle
      Platooning.
AB  - This paper investigates platoon control of vehicles via the wireless
      communication network. An integrated longitudinal and lateral control approaches
      for vehicle platooning within a designated lane is proposed. Firstly, the
      longitudinal control aims to regulate the speed of the follower vehicle on the
      leading vehicle while maintaining the inter-distance to the desired value which
      may be chosen proportional to the vehicle speed. Thus, based on Lyapunov
      candidate function, sufficient stability conditions formulated in BMIs terms are
      proposed. For the general objective of string stability and robust platoon
      control to be achieved simultaneously, the obtained controller is complemented by
      additional conditions established for guaranteeing string stability. Furthermore,
      constraints such as actuator saturation, and controller constrained information
      are also considered in control design. Secondly, a multi-model fuzzy controller
      is developed to handle the vehicle lateral control. Its objective is to maintain
      the vehicle within the road through steering. The design conditions are strictly
      expressed in terms of LMIs which can be efficiently solved with available
      numerical solvers. The effectiveness of the proposed control method is validated
      under the CarSim software package.

PMID- 30217086
TI  - QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial Agents.
AB  - Malaria is a disease caused by protozoan parasites of the genus Plasmodium that
      affects millions of people worldwide. In recent years there have been parasite
      resistances to several drugs, including the first-line antimalarial treatment.
      With the aim of proposing new drugs candidates for the treatment of disease,
      Quantitative Structure-Activity Relationship (QSAR) methodology was applied to 83
      N-myristoyltransferase inhibitors, synthesized by Leatherbarrow et al. The QSAR
      models were developed using 63 compounds, the training set, and externally
      validated using 20 compounds, the test set. Ten different alignments for the two
      test sets were tested and the models were generated by the technique that
      combines genetic algorithms and partial least squares. The best model shows r2 =
      0.757, q2adjusted = 0.634, R2pred = 0.746, R2m = 0.716, ?R2m = 0.133, R2p =
      0.609, and R2r = 0.110. This work suggested a good correlation with the
      experimental results and allows the design of new potent N-myristoyltransferase
      inhibitors.

PMID- 30217087
TI  - Theoretical Insights into the Electron Capture Behavior of H2SO4...N2O Complex: A
      DFT and Molecular Dynamics Study.
AB  - Both sulfuric acid (H2SO4) and nitrous oxide (N2O) play a central role in the
      atmospheric chemistry in regulating the global environment and climate changes.
      In this study, the interaction behavior between H2SO4 and N2O before and after
      electron capture has been explored using the density functional theory (DFT)
      method as well as molecular dynamics simulation. The intermolecular interactions
      have been characterized by atoms in molecules (AIM), natural bond orbital (NBO),
      and reduced density gradient (RDG) analyses, respectively. It was found that
      H2SO4 and N2O can form two transient molecular complexes via intermolecular H
      bonds within a certain timescale. However, two molecular complexes can be
      transformed into OH radical, N2, and HSO4- species upon electron capture,
      providing an alternative formation source of OH radical in the atmosphere.
      Expectedly, the present findings not only can provide new insights into the
      transformation behavior of H2SO4 and N2O, but also can enable us to better
      understand the potential role of the free electron in driving the proceeding of
      the relevant reactions in the atmosphere.

PMID- 30217088
TI  - Long Non-Coding RNAs in Gliomas: From Molecular Pathology to Diagnostic
      Biomarkers and Therapeutic Targets.
AB  - Gliomas are the most common malignancies of the central nervous system. Because
      of tumor localization and the biological behavior of tumor cells, gliomas are
      characterized by very poor prognosis. Despite significant efforts that have gone
      into glioma research in recent years, the therapeutic efficacy of available
      treatment options is still limited, and only a few clinically usable diagnostic
      biomarkers are available. More and more studies suggest non-coding RNAs to be
      promising diagnostic biomarkers and therapeutic targets in many cancers,
      including gliomas. One of the largest groups of these molecules is long non
      coding RNAs (lncRNAs). LncRNAs show promising potential because of their unique
      tissue expression patterns and regulatory functions in cancer cells.
      Understanding the role of lncRNAs in gliomas may lead to discovery of the novel
      molecular mechanisms behind glioma biological features. It may also enable
      development of new solutions to overcome the greatest obstacles in therapy of
      glioma patients. In this review, we summarize the current knowledge about lncRNAs
      and their involvement in the molecular pathology of gliomas. A conclusion follows
      that these RNAs show great potential to serve as powerful diagnostic, prognostic,
      and predictive biomarkers as well as therapeutic targets.

PMID- 30217089
TI  - Optimum Power Loads for Elite Boxers: Case Study with the Brazilian National
      Olympic Team.
AB  - The purpose of this case study was to examine the effects of a resistance
      training program based on the optimum power loads (OPL) method on neuromuscular
      performance of Olympic boxing athletes during preparation for the Rio-2016
      Olympic Games. Twelve elite amateur boxers from the Brazilian National Olympic
      Team participated in this study. Athletes were assessed at four time-points, over
      two consecutive competitive seasons. In the first season (considered as "control
      period"), the athletes executed a non-controlled strength-power training program
      for 10 weeks. In the second season (a seven-week experimental period), the elite
      boxers performed 14 power-oriented training sessions, comprising bench press (BP)
      and jump squat (JS) exercises at the OPL. Maximum bar-power output in BP and JS
      exercises was measured pre and post both training phases. Magnitude-based
      inferences were used to compare changes in pre and post training tests. Bar-power
      outputs increased meaningfully in both BP (+8%) and JS (+7%) exercises after the
      OPL training program. In contrast, after the control period, no worthwhile
      improvements were observed in the variables tested. Based on the findings of this
      study, highly trained boxers might benefit from the use of a training scheme
      based on OPL.

PMID- 30217090
TI  - "Seeing What's Left": The Effect of Position of Transparent Windows on Product
      Evaluation.
AB  - The position of design elements on product packaging has been shown to exert a
      measurable impact on consumer perception across a number of different studies and
      product categories. Design elements previously found to influence the consumer
      through their positioning on the front of pack include product imagery, brand
      logos, text-based claims, and basic shapes. However, as yet, no empirical
      research has focused specifically on the relative position of transparent
      windows; despite the latter being an increasingly prevalent element of many
      modern packaging designs. This exploratory online study details an experimental
      investigation of how manipulating the position of a transparent window on a range
      of visually-presented, novel packaging designs influences consumer evaluations
      and judgements of the product seen within. Specifically, 110 participants rated
      24 different packaging designs (across four product categories: granola, boxed
      chocolates, pasta, and lemon mousse; each with six window positions: in one of
      the four quadrants, the top half, or the bottom half) in a within-participants
      experimental design. Analyses were conducted using Friedman's tests and Hochberg
      procedure-adjusted Wilcoxon Signed-Rank Tests. Window position was found to be a
      non-trivial element of design, with a general preference for windows on the right
      hand side being evidenced. Significantly higher scores for expected product
      tastiness and design attractiveness were consistently identified across all
      product categories when windows were positioned on the right- vs. left-hand side
      of the packaging. Effects on the perception of powerfulness, overall liking,
      quality, and willingness to purchase were identified, but were inconsistent
      across the different product categories. Very few effects of window verticality
      were identified, with expected weight of the product not being significantly
      influenced by window position. The implications of these findings for academics,
      designers, and brand managers are discussed, with future research directions
      highlighted.

PMID- 30217091
TI  - A Novel Fault Detection with Minimizing the Noise-Signal Ratio Using
      Reinforcement Learning.
AB  - In this paper, a reinforcement learning approach is proposed to detect unexpected
      faults, where the noise-signal ratio of the data series is minimized to achieve
      robustness. Based on the information of fault free data series, fault detection
      is promptly implemented by comparing with the model forecast and real-time
      process. The fault severity degrees are also discussed by measuring the distance
      between the healthy parameters and faulty parameters. The effectiveness of the
      algorithm is demonstrated by an example of a DC-motor system.

PMID- 30217092
TI  - Predicting Spatial Variations in Soil Nutrients with Hyperspectral Remote Sensing
      at Regional Scale.
AB  - Rapid acquisition of the spatial distribution of soil nutrients holds great
      implications for farmland soil productivity safety, food security and
      agricultural management. To this end, we collected 1297 soil samples and measured
      the content of soil total nitrogen (TN), soil available phosphorus (AP) and soil
      available potassium (AK) in Zengcheng, north of the Pearl River Delta, China.
      Hyperspectral remote sensing images (115 bands) of the Chinese Environmental 1A
      satellite were used as auxiliary variables and dimensionality reduction was
      performed using Pearson correlation analysis and principal component analysis.
      The TN, AP and AK of soil were predicted in the study area based on auxiliary
      variables after dimensionality reduction, along with stepwise linear regression
      (SLR), support vector machine (SVM), random forest (RF) and back-propagation
      neural network (BPNN) models; 324 independent points were used to verify the
      predictive performance. The BPNN model, which demonstrated the best predictive
      accuracy among all methods, combined ordinary kriging (OK) with mapping the
      spatial variations of soil nutrients. Results show that the BPNN model with
      double hidden layers had better predictive accuracy for soil TN (root mean square
      error (RMSE) = 0.409 mg kg-1, R2 = 44.24%), soil AP (RMSE = 40.808 mg kg-1, R2 =
      42.91%) and soil AK (RMSE = 67.464 mg kg-1, R2 = 48.53%) compared with the SLR,
      SVM and RF models. The back propagation neural network-ordinary kriging (BPNNOK)
      model showed the best predictive results of soil TN (RMSE = 0.292 mg kg-1, R2 =
      68.51%), soil AP (RMSE = 29.62 mg kg-1, R2 = 69.30%) and soil AK (RMSE = 49.67 mg
      kg-1 and R2 = 70.55%), indicating the best fitting ability between hyperspectral
      remote sensing bands and soil nutrients. According to the spatial mapping results
      of the BPNNOK model, concentrations of soil TN (north-central), soil AP (central
      and southwest) and soil AK (central and southeast) were respectively higher in
      the study area. The most important bands (464-517 nm) for soil TN (b10, b14, b20
      and b21), soil AP (b3, b19 and b22) and soil AK (b4, b11, b12 and b25) exhibited
      the best response and sensitivity according to the SLR, SVM, RF and BPNN models.
      It was concluded that the application of hyperspectral images (visible-near
      infrared data) with BPNNOK model was found to be an efficient method for mapping
      and monitoring soil nutrients at the regional scale.

PMID- 30217094
TI  - Design and Implementation of an Infrared Radiant Source for Humidity Testing.
AB  - A novel way to measure humidity through testing the emissivity of an area radiant
      source is presented in this paper. The method can be applied in the environment
      at near room temperature (5~95  degrees C) across the relative humidity (RH)
      range of 20~90% RH. The source, with a grooved radiant surface, works in the far
      infrared wavelength band of 8~12 MUm. The Monte-Carlo model for thermal radiation
      was set up to analyze the V-grooved radiant surface. Heat pipe technology is used
      to maintain an isothermal radiant surface. The fuzzy-PID control method was
      adopted to solve the problems of intense heat inertia and being easily interfered
      by the environment. This enabled the system to be used robustly across a large
      temperature range with high precision. The experimental results tested with a
      scanning radiant thermometer showed that the radiant source can provide a uniform
      thermal radiation capable of satisfying the requirements of humidity testing. The
      calibration method for the radiant source for humidity was explored, which is
      available for testing humidity.

PMID- 30217095
TI  - Retinoids Issued from Hepatic Stellate Cell Lipid Droplet Loss as Potential
      Signaling Molecules Orchestrating a Multicellular Liver Injury Response.
AB  - Hepatic stellate cells (HSCs) serve as the main body storage compartment for
      vitamin A through retinyl ester (RE)-filled lipid droplets (LDs). Upon liver
      injury, HSCs adopt a myofibroblastic phenotype characterized by an elevated
      expression of extracellular matrix proteins and a concomitant loss of LDs. On the
      one hand, LD breakdown has been suggested to provide the energy required for HSC
      activation into myofibroblast-like cells. On the other hand, this process could
      mitigate HSC activation following the transformation of released REs into
      retinoic acids (RAs), ligands for nuclear receptors exerting antifibrotic
      transcriptional regulatory activities in HSCs. Importantly, RAs may also
      constitute a means for HSCs to orchestrate the liver response to injury by
      triggering transcriptional effects in multiple additional surrounding liver cell
      populations. We envision that new approaches, such as single-cell technologies,
      will allow to better define how RAs are issued from LD loss in HSCs exert a
      multicellular control of the liver (patho)physiology.

PMID- 30217096
TI  - The Potential Role of Auxin and Abscisic Acid Balance and FtARF2 in the Final
      Size Determination of Tartary Buckwheat Fruit.
AB  - Tartary buckwheat is a type of cultivated medicinal and edible crop with good
      economic and nutritional value. Knowledge of the final fruit size of buckwheat is
      critical to its yield increase. In this study, the fruit development of two
      species of Tartary buckwheat in the Polygonaceae was analyzed. During fruit
      development, the size/weight, the contents of auxin (AUX)/abscisic acid (ABA),
      the number of cells, and the changes of embryo were measured and observed; and
      the two fruit materials were compared to determine the related mechanisms that
      affected fruit size and the potential factors that regulated the final fruit
      size. The early events during embryogenesis greatly influenced the final fruit
      size, and the difference in fruit growth was primarily due to the difference in
      the number of cells, implicating the effect of cell division rate. Based on our
      observations and recent reports, the balance of AUX and ABA might be the key
      factor that regulated the cell division rate. They induced the response of auxin
      response factor 2 (FtARF2) and downstream small auxin upstream RNA (FtSAURs)
      through hormone signaling pathway to regulate the fruit size of Tartary
      buckwheat. Further, through the induction of fruit expansion by exogenous auxin,
      FtARF2b was significantly downregulated. The FtARF2b is a potential target for
      molecular breeding or gene editing.

PMID- 30217093
TI  - Zoonotic Potential of Influenza A Viruses: A Comprehensive Overview.
AB  - Influenza A viruses (IAVs) possess a great zoonotic potential as they are able to
      infect different avian and mammalian animal hosts, from which they can be
      transmitted to humans. This is based on the ability of IAV to gradually change
      their genome by mutation or even reassemble their genome segments during co
      infection of the host cell with different IAV strains, resulting in a high
      genetic diversity. Variants of circulating or newly emerging IAVs continue to
      trigger global health threats annually for both humans and animals. Here, we
      provide an introduction on IAVs, highlighting the mechanisms of viral evolution,
      the host spectrum, and the animal/human interface. Pathogenicity determinants of
      IAVs in mammals, with special emphasis on newly emerging IAVs with pandemic
      potential, are discussed. Finally, an overview is provided on various approaches
      for the prevention of human IAV infections.

PMID- 30217098
TI  - Morphometric Analysis of One-Component Polyurethane Foams Applicable in the
      Building Sector via X-ray Computed Microtomography.
AB  - A detailed morphometric analysis of one-component polyurethane (PU) expanding
      foams, with densities of 26 and 28 kg/m3 ('SUMMER' and 'WINTER' product
      versions), was conducted to evaluate the topology of the foam cells and to
      discover processing-to-structure relationships. The microstructural analysis of
      the heterogeneously distributed pores revealed tight relationships between the
      foam morphology and the cell topology, depending on the growth rate and local
      environmental conditions, governed by the properties of the blowing gas used. The
      most significant morphometric output included the following: open/closed porosity
      and (heterogeneous) pore distribution, relative density and (homogeneous) strut
      distribution, and total solid matrix surface and closed pore surface area-at the
      macroscopic level of the foam. While, at the microscopic level of the cells, the
      results embraced the following: the size of every detected strut and pore,
      identified two-dimensional (2D) shapes of the cell faces, and proposed three
      dimensional (3D) topologies modelling the PU foam cells. The foam microstructure
      could be then related with macroscopic features, significant in building
      applications. Our protocol outlines the common procedures that are currently used
      for the sample preparation, X-ray scanning, 3D image reconstruction and dataset
      analysis in the frame of the X-ray computed microtomography (u-CT) testing of the
      one-component PU foams, followed by a statistical (multiple Gaussian) analysis
      and conceptual considerations of the results in comparison with thematic
      literature.

PMID- 30217097
TI  - Biomedical Porous Shape Memory Alloys for Hard-Tissue Replacement Materials.
AB  - Porous shape memory alloys (SMAs), including NiTi and Ni-free Ti-based alloys,
      are unusual materials for hard-tissue replacements because of their unique
      superelasticity (SE), good biocompatibility, and low elastic modulus. However,
      the Ni ion releasing for porous NiTi SMAs in physiological conditions and
      relatively low SE for porous Ni-free SMAs have delayed their clinic applications
      as implantable materials. The present article reviews recent research progresses
      on porous NiTi and Ni-free SMAs for hard-tissue replacements, focusing on two
      specific topics: (i) synthesis of porous SMAs with optimal porous structure,
      microstructure, mechanical, and biological properties; and, (ii) surface
      modifications that are designed to create bio-inert or bio-active surfaces with
      low Ni releasing and high biocompatibility for porous NiTi SMAs. With the
      advances of preparation technique, the porous SMAs can be tailored to satisfied
      porous structure with porosity ranging from 30% to 85% and different pore sizes.
      In addition, they can exhibit an elastic modulus of 0.4-15 GPa and SE of more
      than 2.5%, as well as good cell and tissue biocompatibility. As a result, porous
      SMAs had already been used in maxillofacial repairing, teeth root replacement,
      and cervical and lumbar vertebral implantation. Based on current research
      progresses, possible future directions are discussed for "property-pore
      structure" relationship and surface modification investigations, which could lead
      to optimized porous biomedical SMAs. We believe that porous SMAs with optimal
      porous structure and a bioactive surface layer are the most competitive candidate
      for short-term and long-term hard-tissue replacement materials.

PMID- 30217099
TI  - Precision and Accuracy of a Direct-Reading Miniaturized Monitor in PM2.5 Exposure
      Assessment.
AB  - The aim of this study was to evaluate the precision, accuracy, practicality, and
      potential uses of a PM2.5 miniaturized monitor (MM) in exposure assessment. These
      monitors (AirBeam, HabitatMap) were compared with the widely used direct-reading
      particulate matter monitors and a gravimetric reference method for PM2.5.
      Instruments were tested during 20 monitoring sessions that were subdivided in two
      different seasons to evaluate the performance of sensors across various
      environmental and meteorological conditions. Measurements were performed at an
      urban background site in Como, Italy. To evaluate the performance of the
      instruments, different analyses were conducted on 8-h averaged PM2.5
      concentrations for comparison between direct-reading monitors and the gravimetric
      method, and minute-averaged data for comparison between the direct-reading
      instruments. A linear regression analysis was performed to evaluate whether the
      two measurement methods, when compared, could be considered comparable and/or
      mutually predictive. Further, Bland-Altman plots were used to determine whether
      the methods were characterized by specific biases. Finally, the correlations
      between the error associated with the direct-reading instruments and the
      meteorological parameters acquired at the sampling point were investigated.
      Principal results show a moderate degree of agreement between MMs and the
      reference method and a bias that increased with an increase in PM2.5
      concentrations.

PMID- 30217102
TI  - A Review of Planar PIV Systems and Image Processing Tools for Lab-On-Chip
      Microfluidics.
AB  - Image-based sensor systems are quite popular in micro-scale flow investigations
      due to their flexibility and scalability. The aim of this manuscript is to
      provide an overview of current technical possibilities for Particle Image
      Velocimetry (PIV) systems and related image processing tools used in
      microfluidics applications. In general, the PIV systems and related image
      processing tools can be used in a myriad of applications, including (but not
      limited to): Mixing of chemicals, droplet formation, drug delivery, cell
      counting, cell sorting, cell locomotion, object detection, and object tracking.
      The intention is to provide some application examples to demonstrate the use of
      image processing solutions to overcome certain challenges encountered in
      microfluidics. These solutions are often in the form of image pre- and post
      processing techniques, and how to use these will be described briefly in order to
      extract the relevant information from the raw images. In particular, three main
      application areas are covered: Micro mixing, droplet formation, and flow around
      microscopic objects. For each application, a flow field investigation is
      performed using Micro-Particle Image Velocimetry (uPIV). Both two-component (2C)
      and three-component (3C) uPIV systems are used to generate the reported results,
      and a brief description of these systems are included. The results include
      detailed velocity, concentration and interface measurements for micromixers,
      phase-separated velocity measurements for the micro-droplet generator, and time
      resolved (TR) position, velocity and flow fields around swimming objects.
      Recommendations on, which technique is more suitable in a given situation are
      also provided.

PMID- 30217100
TI  - Ambiguous Effects of Autophagy Activation Following Hypoperfusion/Ischemia.
AB  - Autophagy primarily works to counteract nutrient deprivation that is strongly
      engaged during starvation and hypoxia, which happens in hypoperfusion.
      Nonetheless, autophagy is slightly active even in baseline conditions, when it is
      useful to remove aged proteins and organelles. This is critical when the
      mitochondria and/or proteins are damaged by toxic stimuli. In the present review,
      we discuss to that extent the recruitment of autophagy is beneficial in
      counteracting brain hypoperfusion or, vice-versa, its overactivity may per se be
      detrimental for cell survival. While analyzing these opposite effects, it turns
      out that the autophagy activity is likely not to be simply good or bad for cell
      survival, but its role varies depending on the timing and amount of autophagy
      activation. This calls for the need for an appropriate autophagy tuning to
      guarantee a beneficial effect on cell survival. Therefore, the present article
      draws a theoretical pattern of autophagy activation, which is hypothesized to
      define the appropriate timing and intensity, which should mirrors the duration
      and severity of brain hypoperfusion. The need for a fine tuning of the autophagy
      activation may explain why confounding outcomes occur when autophagy is studied
      using a rather simplistic approach.

PMID- 30217101
TI  - Effects of Polyphenols on Thermogenesis and Mitochondrial Biogenesis.
AB  - Obesity is a health problem worldwide, and energy imbalance has been pointed out
      as one of the main factors responsible for its development. As mitochondria are a
      key element in energy homeostasis, the development of obesity has been strongly
      associated with mitochondrial imbalance. Polyphenols are the largest group of
      phytochemicals, widely distributed in the plant kingdom, abundant in fruits and
      vegetables, and have been classically described as antioxidants owing to their
      well-established ability to eliminate free radicals and reactive oxygen species
      (ROS). During the last decade, however, growing evidence reports the ability of
      polyphenols to perform several important biological activities in addition to
      their antioxidant activity. Special attention has been given to the ability of
      polyphenols to modulate mitochondrial processes. Thus, some polyphenols are now
      recognized as molecules capable of modulating pathways that regulate
      mitochondrial biogenesis, ATP synthesis, and thermogenesis, among others. The
      present review reports the main benefits of polyphenols in modulating
      mitochondrial processes that favor the regulation of energy expenditure and offer
      benefits in the management of obesity, especially thermogenesis and mitochondrial
      biogenesis.

PMID- 30217103
TI  - Core-Shell-Structured Particle Reinforced A356 Matrix Composite Prepared by
      Powder-Thixoforming: Effect of Reheating Temperature.
AB  - A novel core-shell-structured Ti-(Al-Si-Ti) particle (Ti-(Al-Si-Ti)p) reinforced
      A356 matrix composite was fabricated by a new method, powder thixoforming, which
      combines the merits of both powder metallurgy and semisolid thixoforming. The
      effects of reheating temperature on the microstructure and tensile properties of
      the resulting composite were investigated. The results indicated that the
      thickening of the Al-Si-Ti compound shells, with rising the reheating
      temperature, significantly enhanced the strengthening role, but the fracture and
      peeling of the shells, at higher than 600  degrees C, impaired the strengthening
      effect. The composite formed at 600  degrees C had a favorable tensile elongation
      of 8.3% besides high tensile strengths. During tensile testing, the Ti@(Al-Si
      Ti)p frequently fractured across the Ti cores and occasionally cracked around the
      Ti cores, but preferentially fractured between the outer cracked shells and the
      inner cores for the composites thixoformed at higher than 600  degrees C. The
      delayed formation of cracks in the Ti-(Al-Si-Ti)p and the small size of the
      cracks contributed to ductility improvement. The MSL model, modified according to
      the Ti@(Al-Si-Ti)p characteristics, was essentially suitable for predicting the
      yield strength of such composites. The largest contribution to the strength was
      resulted from solid solution strengthening of Ti element, but the strengthening
      role from geometrically necessary dislocations was significantly improved as the
      reheating temperature rose from 590  degrees C to 600  degrees C.

PMID- 30217104
TI  - In Vitro Antimicrobial Activity of Essential Oils from Sardinian Flora against
      Cutibacterium (Formerly Propionibacterium) acnes and Its Enhancement by Chitosan.
AB  - The in vitro antibacterial activity of some essential oils from Sardinian flora,
      both alone and in combination with chitosan, was investigated against a strain of
      Cutibacterium acnes, a bacterium involved in pathogenesis of acne. The
      composition of the essential oils was determined by gas chromatography and gas
      chromatography/mass spectrometry. The results of this investigation demonstrated
      that some of the oils examined, characterised by different chemical profiles,
      possessed some activity against C. acnes. Interestingly, this antibacterial
      effect was enhanced by sub-inhibitory concentrations of chitosan. These
      observations suggest the potential application of this synergy in the development
      of innovative topical formulations useful in the management of acne.

PMID- 30217105
TI  - An Optimal Radial Basis Function Neural Network Enhanced Adaptive Robust Kalman
      Filter for GNSS/INS Integrated Systems in Complex Urban Areas.
AB  - Inertial Navigation System (INS) is often combined with Global Navigation
      Satellite System (GNSS) to increase the positioning accuracy and continuity. In
      complex urban environments, GNSS/INS integrated systems suffer not only from
      dynamical model errors but also GNSS observation gross errors. However, it is
      hard to distinguish dynamical model errors from observation gross errors because
      the observation residuals are affected by both of them in a loosely-coupled
      integrated navigation system. In this research, an optimal Radial Basis Function
      (RBF) neural network-enhanced adaptive robust Kalman filter (KF) method is
      proposed to isolate and mitigate the influence of the two types of errors. In the
      proposed method, firstly a test statistic based on Mahalanobis distance is
      treated as judging index to achieve fault detection. Then, an optimal RBF neural
      network strategy is trained on-line by the optimality principle. The network's
      output will bring benefits in recognizing the above two kinds of filtering fault
      and the system is able to choose a robust or adaptive Kalman filtering method
      autonomously. A field vehicle test in urban areas with a low-cost GNSS/INS
      integrated system indicates that two types of errors simulated in complex urban
      areas have been detected, distinguished and eliminated with the proposed scheme,
      success rate reached up to 92%. In particular, we also find that the novel neural
      network strategy can improve the overall position accuracy during GNSS signal
      short-term outages.

PMID- 30217106
TI  - A Comparative Study of Phosphatidylcholine versus Phosphatidylserine-Based Solid
      Supported Membranes for the Preparation of Liposome-Rich Interfaces.
AB  - Solid supported membranes (SSMs) are usually formed by an hybrid
      octadecanethiol/phosphatidylcholine (PC) bilayer supported by a gold electrode.
      Recently, it was shown that phosphatidylserine (PS) in place of PC can promote a
      more effective accumulation of lipid vesicles on the SSM surface when Ca2+ and
      Mg2+ ions are present in the external environment. Here we performed a detailed
      comparative study of the vesicle adsorption process onto PC- and PS-SSMs by
      employing surface plasmon resonance (SPR), electrochemical impedance spectroscopy
      (EIS), and atomic force microscopy (AFM). SPR analysis has demonstrated a higher
      affinity of the PS-SSM surface for the phospholipid vesicles. Both SPR and EIS
      measurements suggest that adsorption of lipid vesicles on the PC-SSM tends to a
      saturating value, whereas a continuous and progressive vesicle adsorption occurs
      on the PS-SSM surface following subsequent liposome additions. AFM analysis
      pointed out a systematic flattening of the adsorbed vesicles on the PS-SSM
      surface. We interpreted our results as due to the strong coordinating action of
      the high amount of divalent cations accumulated at the negatively charged PS-SSM
      surface, whereas a lower amount of cations is present on the dipolar PC-SSM
      surface, which can therefore adsorb only a limited number of vesicles.

PMID- 30217107
TI  - Competitive Adsorption of ZrO2 Nanoparticle and Alkali Cations (Li+-Cs+) on
      Muscovite (001).
AB  - We studied the adsorption behavior of ZrO2 nanoparticles on a muscovite (001)
      surface in the presence of cations from the alkali series (Li+, Na+, K+, Rb+, and
      Cs+). The results of X-ray reflectivity, i.e., specular crystal truncation rod
      and resonant anomalous X-ray reflectivity in combination with AFM images, show
      that the sorption of ZrO2 nanoparticles is significantly affected by the binding
      mode of alkali ions on the muscovite (001) surface. From solutions containing
      alkali ions binding as outer sphere surface complexes (i.e., Li+ and Na+), higher
      uptake of Zr4+ is observed corresponding to the binding of larger nanoparticles,
      which relatively easily replace the loosely bound alkali ions. However, Zr4+
      uptake in solutions containing alkali ions binding as inner sphere surface
      complexes (i.e., K+, Rb+, and Cs+) is significantly lower, and smaller
      nanoparticles are found at the interface. In addition, the uptake of Zr4+ in the
      presence of inner sphere bound cations displays a strong linear relationship with
      the hydration energy of the coexisting alkali ion. The linear trend can be
      interpreted as competitive adsorption between ZrO2 nanoparticles and inner sphere
      bound alkali cations, which are replaced on the surface and undergo rehydration
      after release to the solution. The rehydration of alkali ions gives rise to a
      large energy gain, which dominates the reaction energy of the competitive
      adsorption process. The competitive adsorption mechanism of ZrO2 nanoparticles
      and alkali ions is discussed comprehensively to highlight the potential
      relationship between the hydration effect of alkali ions and the effect of charge
      density of the nanoparticles.

PMID- 30217108
TI  - Ir(III)-Catalyzed Stereoselective Haloamidation of Alkynes Enabled by Ligand
      Participation.
AB  - Described herein is the application of a strategy of ligand participation for the
      Ir-catalyzed imido transfer into alkynes. On the basis of a stoichiometric [3 +
      2] cycloaddition of Cp*Ir(III)(kappa2- N, O-chelate) with alkynyl dioxazolone, a
      catalytic haloamidation was developed for the first time by employing [Cp*IrCl2]2
      precatalyst and NaX salts (X = Cl or Br) as practical halide sources to furnish
      synthetically versatile Z-(halovinyl)lactams with excellent stereoselectivity.

PMID- 30217109
TI  - Encapsulation of Vitamin E and Soy Isoflavone Using Spiral Dextrin: Comparative
      Structural Characterization, Release Kinetics, and Antioxidant Capacity during
      Simulated Gastrointestinal Tract.
AB  - Spiral dextrin subfraction (SD-40) obtained through enzyme debranching and
      gradient ethanol precipitation could interact with vitamin E (VE) or soy
      isoflavone (SIO) to form V-type inclusion complexes. The formation of two
      inclusion complexes was confirmed by Fourier transform-infrared spectroscopy,
      atomic force microscopy, and differential scanning calorimetry. In this study, an
      in vitro gastrointestinal model was used to investigate the breakdown of
      inclusion complexes and release behavior of bioactive compounds. The results
      indicated that the two inclusion complexes exhibited a controlled and sustained
      release behavior during digestion. In addition, the SD-40/VE inclusion complex
      presented higher stability and stronger antioxidant capacity than the SD-40/SIO
      inclusion complex. Furthermore, the first and zero order models were applied to
      understand the release kinetics of VE and SIO from inclusion complexes in the
      stomach, whereas the first order model was chosen to describe the release of VE
      and SIO from inclusion complexes in the intestine.

PMID- 30217110
TI  - Release of Retained Single-Walled Carbon Nanotubes in Gels.
AB  - The separation of single-chirality, even-enantiomeric single-walled carbon
      nanotubes (SWCNTs) has been well established using gel permeation chromatography.
      Successful SWCNTs separation has been considered to be the selective adsorption
      and desorption of specific SWCNTs on the porous sites of Sephacryl gels. This
      work reports two nonspecific releases of SWCNTs retained on Sephacryl gels: (1) a
      considerable number of SWCNTs were eluted using a low-concentration SDS condition
      solution (0.5 wt %) from the gels exclusively eluted with a high-concentration
      SDS eluting solution (5 wt %) after being stocked overnight and (2) the retained
      SWCNTs in Sephacryl gels can be eluted using a low-concentration SDS condition
      solution (0.5 wt %) after being stocked overnight without any treatments.
      Inspired by extracellular matrix systems, these releases are attributed to the
      strain-induced gel relaxation. The roles of surfactants, especially SDS, in the
      retention and release of SWCNTs on Sephacryl gels were discussed on the basis of
      spectral dilution and titration experiments using single-chirality (6,5) SWCNT as
      the probe.

PMID- 30217111
TI  - Converged Colored Noise Path Integral Molecular Dynamics Study of the Zundel
      Cation Down to Ultralow Temperatures at Coupled Cluster Accuracy.
AB  - For a long time, performing converged path integral simulations at ultralow but
      finite temperatures of a few Kelvin has been a nearly impossible task. However,
      recent developments in advanced colored noise thermostatting schemes for path
      integral simulations, namely, the Path Integral Generalized Langevin Equation
      Thermostat (PIGLET) and the Path Integral Quantum Thermal Bath (PIQTB), have been
      able to greatly reduce the computational cost of these simulations, thus making
      the ultralow temperature regime accessible in practice. In this work, we
      investigate the influence of these two thermostatting schemes on the description
      of hydrogen-bonded systems at temperatures down to a few Kelvin as encountered,
      for example, in helium nanodroplet isolation or tagging photodissociation
      spectroscopy experiments. For this purpose, we analyze the prototypical hydrogen
      bond in the Zundel cation (H5O2+) as a function of both oxygen-oxygen distance
      and temperature in order to elucidate how the anisotropic quantum delocalization
      and, thus, the shape of the shared proton adapts depending on the donor-acceptor
      distance. The underlying electronic structure of the Zundel cation is described
      in terms of Behler's Neural Network Potentials of essentially converged Coupled
      Cluster accuracy, CCSD(T*)-F12a/AVTZ. In addition, the performances of the PIQTB
      and PIGLET methods for energetic, structural, and quantum delocalization
      properties are assessed and directly compared. Overall, our results emphasize the
      validity and practical usefulness of these two modern thermostatting approaches
      for path integral simulations of hydrogen-bonded systems even at ultralow
      temperatures.

PMID- 30217112
TI  - Nondestructive Monitoring of the Dispersion State of Titanium Dioxide
      Nanoparticles in Concentrated Suspensions Using Magnetic Resonance Imaging.
AB  - The purpose of the present study is to demonstrate the applicability of magnetic
      resonance imaging, especially T2 relaxation time mapping, for nondestructive
      monitoring of the dispersion state of nanoparticles (NPs) in concentrated
      suspensions. TiO2 15-nm-diameter NPs, for use in sunscreen lotion products, were
      examined as a test NP. First, this study investigated whether T2 is sensitive to
      the NP concentration. In experiments with pulsed nuclear magnetic resonance on
      TiO2 NP suspensions with different organic solvents (ethanol, acetone, and
      decamethylcyclopentasiloxane), the T2 of each solvent varied in the suspensions
      according to the NP concentration. This study also confirmed that T2 mapping was
      effective for visualizing differences in NP concentration. Subsequently,
      gravitational sedimentation of the test suspensions was investigated. T2 mapping
      exhibited better detection sensitivity to sedimentation occurring in concentrated
      suspensions than visual observation, as it enabled the detection of changes in NP
      distributions that could not be visible to the naked eye. In addition,
      measurements of backscattered light enabled the full understanding of the
      dispersion stability of the TiO2 NPs in each solvent. Finally, the present study
      evaluated the centrifuge sedimentation of a commercial TiO2 NP suspension. T2
      mapping clearly showed the complicated sedimentation behavior induced by the
      centrifugation treatment. The simulated fluid flow was consistent with the
      particle distribution in the centrifuged sample; thus, the sedimentation was
      believed to have developed in accordance with the vorticity generated by the
      centrifugation.

PMID- 30217113
TI  - Enhanced Electrophilicity of Heterobimetallic Bi-Rh Paddlewheel Carbene
      Complexes: A Combined Experimental, Spectroscopic, and Computational Study.
AB  - Dirhodium paddlewheel complexes are indispensable tools in modern organometallic
      catalysis for the controlled decomposition of diazo-compounds. Tuning the
      reactivity of the thus-formed transient carbenes remains an active and dynamic
      field of research. Herein, we present our findings that the distal metal center
      plays an as yet underappreciated role in modulating this reactivity. Replacement
      of one rhodium atom in the bimetallic core for bismuth results in the formation
      of a significantly more electrophilic carbene complex. Bismuth-rhodium catalysts
      thereby facilitate previously unknown modes of reactivity for alpha-diazoester
      compounds, including the cyclopropanation of alkenes as electron deficient as
      trichloroethylene. While dirhodium paddlewheel complexes remain the catalysts of
      choice for many carbene-mediated transformations, their bismuth-rhodium analogues
      exhibit complementary reactivity and show great potential for small molecule and
      solvent activation chemistry. DFT calculations highlight the importance of metal
      metal bonding interactions in controlling carbene electrophilicity. The paucity
      of these interactions between the 4d orbitals of rhodium and the 6p orbitals of
      bismuth results in weaker pi-back-bonding interactions for bismuth-rhodium
      carbene complexes compared to dirhodium carbene complexes. This leads to
      weakening of the rhodium-carbene bond and to a more carbene-centered LUMO,
      accounting for the observed enhancement in bismuth-rhodium carbene
      electrophilicity. These findings are supported by a detailed spectroscopic study
      of the "donor-donor" carbene complexes Rh2(esp)2C( p-MeOPh)2 (19) and
      BiRh(esp)2C( p-MeOPh)2 (20), employing a combination of UV-vis and resonance
      Raman spectroscopy. The results reveal that carbene chemoselectivity in MRh(L)4
      catalysis can be modulated to a previously unrecognized extent by the distal
      metalloligand.

PMID- 30217115
TI  - Dementia and its relationship with suicidality: A critical interpretive
      synthesis.
AB  - Objectives The objective of this literature review and synthesis of data was to
      consider the presence, drivers, and protectors of suicidality in people diagnosed
      with dementia. The review also considered what factors represented an increased
      risk of suicidality. Finally, it reflected on the morality and ethics of choice
      when discussing dying in dementia. Method This article used a critical
      interpretive synthesis model which interpreted data associated with the subject
      of suicidality in dementia. A sample frame was used to determine the quality and
      relevance of extracted data, and finally to construct a critical interpretive
      synthesis. Data were extracted from eight key papers. Results The review and
      synthesis concluded with eight synthetic constructs, and two concluding
      synthesised arguments. Argument one was the substantial increased risk of
      suicidality in people diagnosed with dementia and clinical depression. The second
      argument was that end-of-life discussions are common place in people with a
      dementia diagnosis and their families. Conclusion Death remains a difficult
      subject for some to discuss, especially when talking about suicidality.
      Nevertheless, having these conversations is possible, even when there are added
      complexities that a dementia diagnosis can bring. These conversations do,
      however, need to be individualized and measured. And, whilst respecting the
      person's pre-morbid wishes, advance decisions and ethics of choice, we also need
      to consider the ongoing arguments of the 'right to life' versus the 'right to
      die'. However, before these conversations can take place, additional suicidality
      risk factors such as a new and early dementia diagnosis and mental health
      comorbidities such as depression need to be acknowledged and addressed.

PMID- 30217116
TI  - Developing an intelligent virtual agent to stratify people with cognitive
      complaints: A comparison of human-patient and intelligent virtual agent-patient
      interaction.
AB  - Previous work on interactions in the memory clinic has shown that conversation
      analysis can be used to differentiate neurodegenerative dementia from functional
      memory disorder. Based on this work, a screening system was developed that uses a
      computerised 'talking head' (intelligent virtual agent) and a combination of
      automatic speech recognition and conversation analysis-informed programming. This
      system can reliably differentiate patients with functional memory disorder from
      those with neurodegenerative dementia by analysing the way they respond to
      questions from either a human doctor or the intelligent virtual agent. However,
      much of this computerised analysis has relied on simplistic, nonlinguistic
      phonetic features such as the length of pauses between talk by the two parties.
      To gain confidence in automation of the stratification procedure, this paper
      investigates whether the patients' responses to questions asked by the
      intelligent virtual agent are qualitatively similar to those given in response to
      a doctor. All the participants in this study have a clear functional memory
      disorder or neurodegenerative dementia diagnosis. Analyses of patients' responses
      to the intelligent virtual agent showed similar, diagnostically relevant
      sequential features to those found in responses to doctors' questions. However,
      since the intelligent virtual agent's questions are invariant, its use results in
      more consistent responses across people - regardless of diagnosis - which
      facilitates automatic speech recognition and makes it easier for a machine to
      learn patterns. Our analysis also shows why doctors do not always ask the same
      question in the exact same way to different patients. This sensitivity and
      adaptation to nuances of conversation may be interactionally helpful; for
      instance, altering a question may make it easier for patients to understand.
      While we demonstrate that some of what is said in such interactions is bound to
      be constructed collaboratively between doctor and patient, doctors could consider
      ensuring that certain, particularly important and/or relevant questions are asked
      in as invariant a form as possible to be better able to identify diagnostically
      relevant differences in patients' responses.

PMID- 30217117
TI  - Safety and effectiveness of abatacept in Japanese non-elderly and elderly
      patients with rheumatoid arthritis in an all-cases post-marketing surveillance.
AB  - OBJECTIVES: To investigate the safety, effectiveness, and risk-benefit balance of
      intravenous abatacept (ABA) in non-elderly (<65 years: NEG) and elderly (>=65
      years: EG) rheumatoid arthritis patients. METHODS: This sub-analysis of an all
      cases postmarketing surveillance in Japan assessed safety in all enrolled
      patients and effectiveness in those with Disease Activity Score 28 based on C
      reactive protein (DAS28-CRP) measurements at >=2 time points including baseline.
      Risk-benefit was evaluated based on infections and DAS28-CRP improvement >1.2.
      RESULTS: The NEG and EG of the safety analysis set comprised 2,170 and 1,712
      patients, respectively; corresponding 6-month ABA retention rates were 80.2% and
      77.1%. The NEG had fewer adverse drug reactions (14.5% vs. 17.2%, p = .021) and
      infections (4.8% vs. 7.2%, p = .002) than the EG. DAS28-CRP changed similarly
      between groups. The proportion of patients with low-risk/high-benefit and high
      risk/low-benefit were 33.1% and 6.9% (NEG) and 29.7% and 9.0% (EG). Low-risk/high
      benefit patients were younger, had shorter disease duration and fewer
      comorbidities, and were with less use of oral glucocorticoid and prior biologics,
      more use of methotrexate and higher DAS28-CRP than high-risk/low-benefit patients
      at baseline. CONCLUSION: ABA was well tolerated and similarly efficacious in the
      EG and NEG. Identification of factors related to low-risk/high-benefit may aid
      appropriate patient selection.

PMID- 30217118
TI  - Efficacy of 4-year denosumab treatment alone or in combination with teriparatide
      in Japanese postmenopausal osteoporotic women.
AB  - PURPOSE: This extended randomized prospective study aimed to compare the 4-year
      clinical outcomes of denosumab treatment alone or in combination with
      teriparatide in treatment-naive postmenopausal Japanese patients with
      osteoporosis. METHODS: Between July 2013 and December 2016, 30 eligible women
      from our previous study were enrolled. After newly adding 17 randomly assigned
      patients, 47 patients were classified into the denosumab alone group (denosumab
      group, n = 22) or denosumab plus teriparatide group (combination group, n = 25).
      Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid
      phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptide of type I
      collagen (NTX), and bone mineral density (BMD) of the lumbar 1-4 vertebrae (L
      BMD) and bilateral total hips (H-BMD) were determined at the first visit and at
      regular time points up to 48 months of treatment to determine percentage changes.
      RESULTS: BAP was significantly decreased from baseline in both groups from 24 to
      48 months, with significant differences at all time points between the groups.
      TRACP-5b and urinary NTX were comparably decreased at every time point in both
      groups versus pretreatment levels. L-BMD was significantly more increased by
      combination therapy over denosumab alone at 24 and 30 months (21.1% increase vs.
      14.2% increase at 48 months). There were no significant differences in H-BMD
      between the groups, although levels tended to be higher in the combination group
      throughout the study period (9.7% increase vs. 6.8% increase at 48 months).
      CONCLUSION: Long-term denosumab and teriparatide combination therapy represents
      an effective treatment option for primary osteoporosis patients with low L-BMD.

PMID- 30217119
TI  - Carbonic anhydrase inhibitors and their potential in a range of therapeutic
      areas.

PMID- 30217120
TI  - Tracking patients with chronic occipital headache after occipital nerve
      decompression surgery: A case series.
AB  - Background The therapeutic benefit of nerve decompression surgeries for chronic
      headache/migraine are controversial. Aim To provide clinical characteristics of
      headache type and treatment outcome of occipital nerve decompression surgery.
      Methods A retrospective review of clinical records. Inclusion criteria were
      evidence of chronic occipital headache with and without migrainous features and
      tenderness of neck muscles, occipital allodynia, and inadequate response to
      prophylactic drugs. Results Surgical decompression of the greater and lesser
      occipital nerves provided complete and extended (3-6 years) relief of new daily
      persistent headache in case 3 (46 year old female), and of chronic post-traumatic
      headache in cases 4 and 6 (35 and 30 year old females, respectively), partial
      relief of chronic headache/migraine in cases 1 and 2 (41 year old female and 36
      year old male), and no relief of episodic (cases 3 and 4) or chronic migraine
      (case 5, 52 year old male), or chronic tension-type headache (case 7, 31 year old
      male). Conclusions As a case series, this study cannot test a hypothesis or
      determine cause and effect. However, the complete elimination of new daily
      persistent headache and post-traumatic headache, and the partial elimination of
      chronic headache/migraine in two patients - all refractory to other treatment
      approaches - supports and justifies the effort to continue to generate data that
      can help determine whether decompression nerve surgeries are beneficial in the
      treatment of certain types of chronic headache.

PMID- 30217121
TI  - Involvement of midkine in autoimmune and autoinflammatory diseases.
AB  - Midkine (MK) is a heparin-binding growth factor that markedly expressed during
      embryogenesis but downregulated to inconsiderable levels in healthy adults.
      However, MK is upregulated during tissue repair and in many pathologic
      conditions, mostly malignancies and inflammatory diseases. MK promotes a number
      of functions in target cells such as migration, proliferation, survival, growth,
      reproduction and repair, angiogenesis, and gene expression. It acts as a pro
      inflammatory cytokine and contributes to chronic inflammation via promoting
      chemotaxis and tissue infiltration of neutrophils and macrophages. Furthermore,
      MK upregulated the production of various inflammatory mediators (i.e. interleukin
      (IL) 6 and IL8). Recent studies have demonstrated strong evidence that MK is
      involved in the onset and progression of autoimmune rheumatic diseases, including
      rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjogren's
      syndrome (SS) and other autoimmune conditions such as multiple sclerosis (MS).
      Additionally, it has been shown that MK is overexpressed in two major clinically
      defined forms of inflammatory bowel diseases (IBD), Crohn's disease (CD) and
      ulcerative colitis (UC), which are classified as autoinflammatory diseases. Taken
      together, MK is involved in the pathogenesis of autoimmune and autoinflammatory
      diseases and may serve as an indicator and biomarker in these conditions.
      Furthermore, MK inhibitors are expected to contribute in the management of these
      diseases.

PMID- 30217122
TI  - Minimal important change and patient acceptable symptom state for patients after
      proximal interphalangeal joint arthroplasty.
AB  - : Our aim was to determine the minimal important change and patient acceptable
      symptom state for pain and the brief Michigan Hand Outcomes Questionnaire in
      patients 1 year after proximal interphalangeaI joint arthroplasty. We analysed
      data of 100 patients from our prospective registry. The minimal important change
      and patient acceptable symptom state were determined with anchor-based methods,
      and patients with better or worse baseline status were examined. The minimal
      important change for pain at rest and during activities, and the brief Michigan
      Hand Outcomes Questionnaire was -1.2, -2.8 and 18, respectively, with
      corresponding patient acceptable symptom state values of 1.5, 2.5 and 64.
      Patients with higher baseline symptoms rated more severe postoperative symptoms
      as acceptable, whereas patients with lower baseline symptoms were only satisfied
      with a low level of pain and high level of hand function. The minimal important
      change and patient acceptable symptom state are useful estimates for patient
      outcomes and study results. LEVEL OF EVIDENCE: IV.

PMID- 30217123
TI  - Recurrent chest pain and dyspnoea in a patient with pulmonary arterial
      hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating, life
      threatening disease with poor prognosis when left untreated. The long-term
      prognosis is definitely influenced by the natural progression of PAH but late
      disease-specific complications may also contribute. CASE SUMMARY: We present a
      patient with a long-standing idiopathic PAH in whom progressive dilatation of
      pulmonary trunk and pulmonary arteries leads to compression of the left main
      coronary artery and the left atrium with hemodynamic compromise. CONCLUSION: With
      the current treatment options, survival in PAH has improved. Guidelines focus on
      more aggressive treatment with initial combination therapy and earlier referral
      for transplantation.

PMID- 30217124
TI  - Restless Feelings: Desiring Direct Contact After Postmortem Organ Donation.
AB  - This article investigates the emergence of a growing demand in the Netherlands:
      the wish of organ donor families and organ recipients to establish contact. Such
      direct contact transgresses both the anonymity and privacy long considered by
      many to be fundamental to organ donation. Legislation prescribes that privacy
      should be safeguarded, but the parties involved increasingly manage to find each
      other. Research is needed to provide insight into the ramifications of direct
      contact, which may inform mourning counseling and psychosocial support. Drawing
      on qualitative interviews with donor's relatives, we analyze the reasons for the
      desire to have direct contact. We seek to understand how meanings are constructed
      and contested through organs at the margins of life and death in the
      individualized and secularized society of the Netherlands. We find that relatives
      struggle with persistent restless feelings after postmortem organ donation and
      may develop a level of personal attachment and assign inalienability to human
      body parts.

PMID- 30217125
TI  - Physical Fitness and Metabolic Syndrome in Brazilian Adolescents: Validity of
      Diagnostic Health Criteria.
AB  - We tested health criteria cutoff points from physical fitness variables proposed
      by the Fitnessgram program for detecting metabolic syndrome ( MetS) in a
      representative sample of 1,035 Brazilian adolescents (565 girls and 470 boys)
      aged 12-20 years. We studied five fitness tests: (a) back-saver sit and reach,
      (b) trunk lift, (c) curl-up, (d) push-up, and (e) progressive aerobic
      cardiovascular endurance run ( PACER), and we defined MetS through the criteria
      of the International Diabetes Federation. We described the predictive performance
      of each fitness test in terms of sensitivity, specificity, and area under the
      curve ( AUC) estimates of the receiver operating characteristic method. The AUCs
      for four tests ( back-saver sit and reach, trunk lift, curl-up, and push-up)
      revealed low accuracy for identifying MetS in both sexes (0.50 >= AUC <= 0.60),
      but AUCs for the PACER test demonstrated good accuracy values between 0.72 (0.68
      0.76) and 0.83 (0.78-0.89). Thus, cutoff points proposed in the Fitnessgram
      program for the PACER test offer an effective means of screening adolescents at
      higher cardiometabolic risk, which, for the age-group used in this study, should
      be from 40.3-44.3 ml/kg/min for boys and 38.6-40.1 ml/kg/min for girls.

PMID- 30217126
TI  - Covert Attention, Temperament, and Looking: A Novel Approach to Studying
      Attention in the Social World.
AB  - The current study examines relations between individual differences in attention
      measured in laboratory and real-world settings. In-laboratory computer-based
      assessments of orienting, phasic alertness, and executive attention as well as
      self-report measures of temperament and attention-related problems were
      administered to 111 undergraduate participants. Participants later completed a
      walking tour of a multistory building while wearing video recording glasses. The
      recordings were subsequently coded for orientation and capture of overt
      attention. Overt attention was correlated with attention-related traits only in
      high-demand walking conditions (stairways). Our findings suggest that individual
      differences should be a more important consideration in attention research. The
      novel methodology piloted here may be especially practical for studying overt
      attention in social settings.

PMID- 30217127
TI  - Meaning Through Attachment: An Integrative Framework.
AB  - We propose an integrative framework, advancing attachment as a vital factor in
      the development and maintenance of meaning throughout life. First, early
      attachment experiences provide a foundation for recognizing patterns and
      acquiring a sense of order and coherence. Furthermore, interactions with
      sensitive attachment figures stimulate mentalization capacities and exploration
      of the inner and outer environment, enabling the formation of complex
      representations of self, others, and the world, ultimately also molding how
      individuals appraise meaning in their lives. Second, attachment security can
      serve as an enduring and powerful resource for handling threats to meaning. When
      confronted with disruptions to meaning, secure attachment provides a coherent set
      of representations to fall back on and maintain or regain a firm sense of order
      and meaning under challenging circumstances. Moreover, by promoting cognitive
      openness and tolerance of ambiguity, secure attachment facilitates flexible and
      realistic adjustment of meaning representations when encountering discrepant
      information.

PMID- 30217128
TI  - Nanoparticle mediated delivery and small molecule triggered activation of
      proteins in the nucleus.
AB  - Protein transfection is a versatile tool to study or manipulate cellular
      processes and also shows great therapeutic potential. However, the repertoire of
      cost effective techniques for efficient and minimally cytotoxic delivery remains
      limited. Mesoporous silica nanoparticles (MSNs) are multifunctional nanocarriers
      for cellular delivery of a wide range of molecules, they are simple and
      economical to synthesize and have shown great promise for protein delivery. In
      this work we present a general strategy to optimize the delivery of active
      protein to the nucleus. We generated a bimolecular Venus based optical sensor
      that exclusively detects active and bioavailable protein for the performance of
      multi-parameter optimization of protein delivery. In conjunction with cell
      viability tests we maximized MSN protein delivery and biocompatibility and
      achieved highly efficient protein transfection rates of 80%. Using the sensor to
      measure live-cell protein delivery kinetics, we observed heterogeneous timings
      within cell populations which could have a confounding effect on function
      studies. To address this problem we fused a split or dimerization dependent
      protein of interest to chemically induced dimerization (CID) components,
      permitting control over its activity following cellular delivery. Using the split
      Venus protein we directly show that addition of a small molecule dimerizer causes
      synchronous activation of the delivered protein across the entire cell
      population. This combination of cellular delivery and triggered activation
      provides a defined starting point for functional studies and could be applied to
      other protein transfection methods.

PMID- 30217129
TI  - Pulmonary vein thrombosis after lobectomy with vein stump closure by ligation.
AB  - Objectives Thrombosis in the pulmonary vein stump after a left upper lobectomy is
      a rare but potentially life-threatening complication, and the pulmonary vein
      stump length plays an important role here. We assessed the frequency and risk
      factors for thrombosis in patients undergoing lobectomy with division of the
      superior pulmonary vein using ligation. Methods We retrospectively reviewed 425
      patients with primary lung cancer who underwent lobectomy or bilobectomy in our
      institution from 2008 to 2016, with contrast-enhanced chest computed tomography
      within a year after lobectomy. The superior pulmonary vein was divided by thread
      ligation, while the inferior pulmonary vein was divided using a linear stapler.
      The pulmonary vein stump length was measured using contrast-enhanced chest
      computed tomography. Results Four (0.9%) of the 425 patients experienced
      thrombosis in the pulmonary vein stump within 6 months after lobectomy. All 4
      patients had undergone a left upper lobectomy, and 4.1% of this subset developed
      thrombus. One patient with a thrombus in the pulmonary vein stump experienced
      renal and cerebral infarction after a left upper lobectomy. The left superior
      pulmonary vein stump was significantly longer than the other pulmonary vein
      stumps. Conclusions Thrombosis in the pulmonary vein stump occurred in 4.1% of
      patients undergoing a left upper lobectomy with pulmonary vein stump closure by
      thread ligation, which is a relatively low frequency. Superior pulmonary vein
      stump closure using thread ligation might help prevent pulmonary vein stump
      thrombus after a left upper lobectomy.

PMID- 30217130
TI  - Primary surgical repair of tetralogy of Fallot at under three months of age.
AB  - Background Classical management of small infants with tetralogy of Fallot has
      involved placement of a Blalock-Taussig shunt followed later by complete repair,
      rather than primary complete repair which is the strategy adopted in larger
      infants. Some advantages of early complete repair compared to a staged strategy
      have been shown. We sought to review our institutional outcomes. Methods Patients
      under 3-months old undergoing complete surgical repair of tetralogy of Fallot in
      our institution between 2005 and 2015 were retrospectively reviewed and compared
      with an older control group matched by anatomical diagnosis and outflow tract
      intervention. Results Fourteen index cases (group A) and 14 controls (group B)
      were identified. At surgery, the median age was 43 days and weight 4.2 kg in
      group A, and 130 days and 6.1 kg in group B. Nine of 14 in group A were admitted
      for surgery as emergencies compared to none in group B. Peak inotrope score (22.3
      vs. 12.8, p = 0.02) and intensive care unit stay (4.4 vs. 2.6 days, p = 0.02)
      were higher in group A. Bypass and crossclamp times, duration of intubation, and
      total length of stay did not differ. Conclusions We conclude that although babies
      undergoing early repair of tetralogy of Fallot have an increased need for
      intensive care support in the early postoperative period, the total length of
      stay is not prolonged despite more emergency admissions. As it is known that
      early repair may reduce long-term morbidity, we propose consideration of earlier
      complete repair of tetralogy of Fallot.

PMID- 30217131
TI  - Tricuspid regurgitation caused by right ventricle compression by pectus
      excavatum.

PMID- 30217132
TI  - Extending the Passive-Sensing Toolbox: Using Smart-Home Technology in
      Psychological Science.
AB  - New smart-home devices provide the opportunity to advance psychological science
      and theory through novel research opportunities in home environments. These
      technologies extend the in vivo research and intervention capabilities afforded
      by other assessment techniques such as Ecological Momentary Assessment methods as
      well as mobile and wearable devices. Smart-home devices contain a multitude of
      sensors capable of continuously and unobtrusively collecting multimodal data
      within home contexts. These devices have some complementary strengths and
      limitations compared with other assessment methods. This article (a) briefly
      reviews data collection methods in home environments, (b) discusses the unique
      advantages of smart-home devices, (c) describes the extant smart-home literature,
      (d) explores how these devices may advance evaluation and refinement of
      psychological theories, (e) describes examples of psychological processes that
      are potential targets for smart-home assessment and intervention, (f) considers
      methodological challenges and barriers, (g) discusses ethical considerations, and
      (h) concludes with a discussion of future directions for research and the merging
      of passive-sensing technologies with active self-report methods. This article
      aims to highlight the potential utility of smart-home devices within
      psychological research to evaluate psychological theories related to behavior
      within the home context.

PMID- 30217133
TI  - Current risk factors for asymptomatic venous thromboembolism in patients
      undergoing total hip arthroplasty.
AB  - OBJECTIVE: A history of venous thromboembolism (VTE) is a risk factor for newly
      formed VTE after total hip arthroplasty (THA). However, its morbidity and
      association with postoperative VTE are not clear and, therefore, were
      investigated in this study. METHODS: Four-hundred and nineteen patients scheduled
      for primary THA were included. We preoperatively identified any VTE factors such
      as obesity, age, and history of VTE by interviewing and duplex ultrasonography
      for all patients, and the patients were assigned into 'high-' or 'low-risk'
      groups, that were the indication whether chemoprophylaxis was administered after
      surgery. Postoperative VTE was also examined on the day 7 by enhanced computed
      tomography (CT) for all patients. RESULTS: Preoperative VTE were detected in 48
      patients (11.4%), and postoperative VTE were found in 44 (10.5%). Linear and
      multivariate logistic regression analysis revealed osteonecrosis and preoperative
      VTE were the independent factors associated with postoperative VTE (Odds ratio
      (OR) 1.0 e-7 and 5.00, respectively). In the survey of each risk group, only
      preoperative VTE was recognized as a risk factor for high-risk group, and longer
      operation time for low-risk group. CONCLUSION: The present study confirmed high
      frequency of preoperative VTE which was still the strongest risk factor for
      postoperative asymptomatic VTE.

PMID- 30217134
TI  - Improved osteogenic differentiation of human dental pulp stem cells in a layer-by
      layer-modified gelatin scaffold.
AB  - Dental pulp stem cell is a new type of mesenchymal stem cell that has a potential
      for tissue regeneration. Gelatin sponges are often used for hemostasis in dental
      surgery. In this study, we aimed to evaluate the dental pulp stem cells'
      proliferation and osteogenic differentiation in different layer-by-layer-modified
      gelatin sponge scaffolds including the G, G + P (gelatin sponge+ poly-l-lysine
      modification), G + M (gelatin sponge + mineralization modification), and G + M +
      P (gelatin sponge + mineralization modification + poly-l-lysine modification)
      groups in vitro and assessed them in vivo. The results showed that dental pulp
      stem cells had a great potential for osteogenic differentiation. In vitro, the G
      + M + P group not only enhanced the adhesion and proliferation of dental pulp
      stem cells but also facilitated their osteogenic differentiation. However,
      alkaline phosphatase activity was prohibited after modification. In vivo, both
      dental pulp stem cells and cells from nude mice grew well on the scaffold, and G
      + M and G + M + P groups could promote the mineralization deposit formation and
      the expression of osteocalcin in osteogenic differentiation of dental pulp stem
      cells. In conclusion, the combination of dental pulp stem cells and G + M + P
      scaffold has a great potential for bone tissue engineering.

PMID- 30217136
TI  - Corrigendum to Periorbital erythema and swelling as a presenting sign of lupus
      erythematosus in tertiary referral centers and literature review.

PMID- 30217135
TI  - Adults' Markers of Face Processing Are Present at Age 6 and Are Interconnected
      Along Development.
AB  - Recent studies on the development of face processing argue for a late,
      quantitative, domain-specific development of face processing, and face memory in
      particular. Most previous findings were based on separately tracking the
      developmental course of face perception skills, comparing performance across
      different age groups. Here, we adopted a different approach studying the
      mechanisms underlying the development of face processing by focusing on how
      different face skills are interrelated over the years (age 6 to adulthood).
      Specifically, we examined correlations within and between different categories of
      tasks: face domain-specific skills involving face recognition based on long-term
      representations (famous face), and short-term memory retention (Cambridge Face
      Memory Test), perceptual face-specific marker (inversion effect), global effects
      in scene perception (global-local task), and the perception of facial
      expressions. Factor analysis revealed that face identity skills have a similar
      pattern of interrelations throughout development, identifying two factors: a face
      domain-specific factor comprising adultlike markers of face processing and a
      general factor incorporating related, but nonspecific perceptual skills. Domain
      specific age-related changes in face recognition entailing short- and long-term
      retention of face representations were observed, along with mature perceptual
      face-specific markers and more general perceptual effects predicting face
      perception skills already at age 6. The results suggest that the domain-specific
      changes in face processing are unlikely to result from developmental changes in
      perceptual skills driving face recognition. Instead, development may either
      involve improvement in the ability to retain face representations in memory or
      changes in the interactions between the perceptual representations of faces and
      their representations in long-term memory.

PMID- 30217137
TI  - Response to "Chronic cerebrospinal venous insufficiency, chlamydia and multiple
      sclerosis": CCSVI, Chlamydia pneumoniae and multiple sclerosis clarification.

PMID- 30217138
TI  - Meta-analyses using real-world data to generate clinical and epidemiological
      evidence: a systematic literature review of existing recommendations.
AB  - OBJECTIVES: To identify existing guidelines, key recommendations, and existing
      limitations regarding the evaluation and use of real-world evidence (RWE) in meta
      analyses (MAs) to generate clinical and epidemiological evidence: a systematic
      review of existing recommendations. METHODS: A literature search was performed in
      April 2017 in MEDLINE and Embase using the Ovid platform, the Cochrane Library,
      and other sources. No specific inclusion and exclusion criteria were applied, and
      no restrictions in timeframe, language, or geographical scope were imposed.
      RESULTS: The search strategy identified 1681 citations; 12 references were
      included in this review. Recommendations within the literature regarding the use
      of RWE in MAs are: (1) it may be useful to extract and analyze adjusted results
      because confounding is expected; (2) testing heterogeneity in the MA of RWE is
      important as it may minimize the potential for bias and generate hypotheses for
      future research; (3) limiting a search <=2 bibliographic databases when
      conducting MAs of RWE will not provide a thorough summary of existing literature;
      and (4) the Meta-analysis Of Observational Studies in Epidemiology (MOOSE)
      checklist is a 35-item checklist developed to allow for more standardized
      reporting of MAs of RWE and address their limitations. LIMITATIONS: (1) No formal
      guidelines were found regarding the use of RWE in MAs; (2) no consensus was found
      on a preferred instrument for the assessment of RWE; and (3) critical appraisal
      of RWE is often omitted from Health Technology Assessment submissions.
      CONCLUSIONS: The inclusion of RWE in MAs may facilitate the confirmation of
      conclusions drawn from randomized controlled trials and, thus, reassure decision
      makers that findings can be extrapolated to real-world populations. However,
      qualitative and quantitative bias may co-exist in MAs of RWE. Reviewers should
      select the most appropriate tools that match the study designs identified in a
      particular systematic review.

PMID- 30217139
TI  - DM-PhyClus: a Bayesian phylogenetic algorithm for infectious disease transmission
      cluster inference.
AB  - BACKGROUND: Conventional phylogenetic clustering approaches rely on arbitrary
      cutpoints applied a posteriori to phylogenetic estimates. Although in practice,
      Bayesian and bootstrap-based clustering tend to lead to similar estimates, they
      often produce conflicting measures of confidence in clusters. The current study
      proposes a new Bayesian phylogenetic clustering algorithm, which we refer to as
      DM-PhyClus (Dirichlet-Multinomial Phylogenetic Clustering), that identifies sets
      of sequences resulting from quick transmission chains, thus yielding easily
      interpretable clusters, without using any ad hoc distance or confidence
      requirement. RESULTS: Simulations reveal that DM-PhyClus can outperform
      conventional clustering methods, as well as the Gap procedure, a pure distance
      based algorithm, in terms of mean cluster recovery. We apply DM-PhyClus to a
      sample of real HIV-1 sequences, producing a set of clusters whose inference is in
      line with the conclusions of a previous thorough analysis. CONCLUSIONS: DM
      PhyClus, by eliminating the need for cutpoints and producing sensible inference
      for cluster configurations, can facilitate transmission cluster detection. Future
      efforts to reduce incidence of infectious diseases, like HIV-1, will need
      reliable estimates of transmission clusters. It follows that algorithms like DM
      PhyClus could serve to better inform public health strategies.

PMID- 30217140
TI  - Cluster analysis of hemorrhagic disease in Missouri's white-tailed deer
      population: 1980-2013.
AB  - BACKGROUND: Outbreaks of deer hemorrhagic disease (HD) have been documented in
      the USA for many decades. In the year 2012, there was a severe HD outbreak in
      Missouri with mortalities reaching approximately 6.9 per thousand. Moreover,
      Missouri accounted for more than 43% of all reported epizootic HD cases in
      captive white-tailed deer. Using the data of suspected HD occurrence in Missouri,
      the primary goal of this paper was to determine if HD in Missouri's white-tailed
      deer occurs in spatial clusters. RESULTS: The main results of the cluster
      analysis are as follows. First, the spatial clusters of years 1980, 1988, 2005
      2007, 2010, 2012, and 2013 suggest patterns of outbreaks every 6-8 years, with a
      potential outbreak in years 2018-2020. Secondly, these spatial clusters were more
      frequent in the central and southern counties. CONCLUSIONS: The clustering
      analyses employed in this study have potential applications for improving
      surveillance programs and designing early warning systems for effective deer
      population management and potentially reducing the number of HD cases.

PMID- 30217141
TI  - A response to readers' comments.
AB  - This is a response to readers' comments on our paper entitled "Critical role of
      NLRP3-caspase-1 pathway in age-dependent isoflurane-induced microglial
      inflammatory response and cognitive impairment" published in the Journal of
      Neuroinflammation this year.

PMID- 30217142
TI  - Effective surveillance systems for vector-borne diseases in urban settings and
      translation of the data into action: a scoping review.
AB  - BACKGROUND: Vector-borne diseases (VBDs) continue to represent a global threat,
      with "old" diseases like malaria, and "emergent" or "re-emergent" ones like Zika,
      because of an increase in international trade, demographic growth, and rapid
      urbanization. In this era of globalization, surveillance is a key element in
      controlling VBDs in urban settings, but surveillance alone cannot solve the
      problem. A review of experiences is of interest to examine other solution
      elements. The objectives were to assess the different means of VBD surveillance
      in urban environments, to evaluate their potential for supporting public health
      actions, and to describe the tools used for public health actions, the
      constraints they face, and the research and health action gaps to be filled. MAIN
      BODY: For this scoping review we searched peer-reviewed articles and grey
      literature published between 2000 and 2016. Various tools were used for data
      coding and extraction. A quality assessment was done for each study reviewed, and
      descriptive characteristics and data on implementation process and
      transferability were analyzed in all studies. After screening 414 full-text
      articles, we retained a total of 79 articles for review. The main targets of the
      articles were arboviral diseases (65.8%) and malaria (16.5%). The positive
      aspects of many studies fit within the framework of integrated vector management.
      Public awareness is considered a key to successful vector control programs.
      Advocacy and legislation can reinforce both empowerment and capacity building.
      These can be achieved by collaboration within the health sector and with other
      sectors. Research is needed to develop well designed studies and new tools for
      surveillance and control. CONCLUSIONS: The need for surveillance systems in urban
      settings in both developing and developed countries was highlighted. Countries
      face the same challenges relating to human, financial, and structural resources.
      These findings also constitute a wake-up call for governments, academia, funders,
      and World Health Organization to strengthen control programs and enhance VBD
      research in urban environments.

PMID- 30217143
TI  - Identification, characterization and expression analysis of transient receptor
      potential channel genes in the oriental fruit fly, Bactrocera dorsalis.
AB  - BACKGROUND: Members of the transient receptor potential (TRP) superfamily are
      proteins that are critical for insects to detect changes in environmental stimuli
      and also play key roles in their sensory physiology. Moreover, this family
      provides potential targets for the design of insecticides. In contrast to a large
      number of studies conducted on Drosophila melanogaster, molecular studies to
      characterize TRP channels in agricultural pests are lacking. RESULTS: In this
      study, we identified 15 TRP channel genes in the genome of a notorious
      agricultural pest, the oriental fruit fly (Bactrocera dorsalis). Comparative
      analysis of the TRP channels (TRPs) in B. dorsalis with those in D. melanogaster,
      Glossina morsitans, Musca domestica and the closely related Ceratitis capitata,
      and TRPs from mosquitoes, Hymenoptera, Lepidoptera, Coleoptera and Hemiptera
      reveals that members of TRPA and TRPP subfamily are most diverse among insects.
      The results also suggest that Tephritidae family have two TRP-Polycystin 2
      members even though most insects either possess just one or none. The highest
      expression levels of these two genes are in the testes of B. dorsalis, implying a
      role in regulating sperm function. We analyzed the expression profiles of the TRP
      channels identified in this study at different life stages using quantitative
      real time PCR. The results of this study demonstrate that all TRP channels are
      mainly expressed in adults, especially at mature stages. The one exception to
      this trend is BdTRPM, which is more highly expressed in the eggs of B. dorsalis,
      implying an important role in early development. We also detected the spatial
      expression of TRP channels in mature adult fruit flies by investigating
      expression levels within various tissues including those involved in sensory
      function, such as antennae, compound eyes, mouthparts, legs, and wings, as well
      as tissues critical for homeostasis and physiology (i.e., Malpighian tubules, the
      brain and gut as well as fat bodies, ovaries, and testes). CONCLUSION: The
      results of this study establish a solid foundation for future functional
      characterization of B. dorsalis TRP channels as well as those of other insects
      and will help future insecticide design targeting these channels.

PMID- 30217144
TI  - Grid-based computational methods for the design of constraint-based parsimonious
      chemical reaction networks to simulate metabolite production: GridProd.
AB  - BACKGROUND: Constraint-based metabolic flux analysis of knockout strategies is an
      efficient method to simulate the production of useful metabolites in microbes.
      Owing to the recent development of technologies for artificial DNA synthesis, it
      may become important in the near future to mathematically design minimum
      metabolic networks to simulate metabolite production. RESULTS: We have developed
      a computational method where parsimonious metabolic flux distribution is computed
      for designated constraints on growth and production rates which are represented
      by grids. When the growth rate of this obtained parsimonious metabolic network is
      maximized, higher production rates compared to those noted using existing methods
      are observed for many target metabolites. The set of reactions used in this
      parsimonious flux distribution consists of reactions included in the original
      genome scale model iAF1260. The computational experiments show that the grid size
      affects the obtained production rates. Under the conditions that the growth rate
      is maximized and the minimum cases of flux variability analysis are considered,
      the developed method produced more than 90% of metabolites, while the existing
      methods produced less than 50%. Mathematical explanations using examples are
      provided to demonstrate potential reasons for the ability of the proposed
      algorithm to identify design strategies that the existing methods could not
      identify. CONCLUSION: We developed an efficient method for computing the design
      of minimum metabolic networks by using constraint-based flux balance analysis to
      simulate the production of useful metabolites. The source code is freely
      available, and is implemented in MATLAB and COBRA toolbox.

PMID- 30217145
TI  - Pseudocohnilembus persalinus genome database - the first genome database of
      facultative scuticociliatosis pathogens.
AB  - BACKGROUND: Pseudocohnilembus persalinus, a unicellular ciliated protozoan, is
      one of commonest facultative pathogens. We sequenced the macronuclear genome of
      P. persalinus in 2015, which provided new insights into its pathogenicity.
      RESULTS: Here, we present the P. persalinus genome database (PPGD) (
      http://ciliates.ihb.ac.cn/database/home/#pp ), the first genome database for the
      scuticociliatosis pathogens. PPGD integrates P. persalinus macronuclear genomic
      and transcriptomic data, including genome sequence, transcript, gene expression
      data, and gene annotation, as well as relevant information on its biology,
      morphology and taxonomy. The database also provides functions for visualizing,
      analyzing, and downloading the data. CONCLUSION: PPGD is a useful resource for
      studying scuticociliates or scuticociliatosis. We will continue to update the
      PPGD by integrating more data and aim to integrate the PPGD with other ciliate
      databases to build a comprehensive ciliate genome database.

PMID- 30217146
TI  - Treponema pallidum promotes macrophage polarization and activates the NLRP3
      inflammasome pathway to induce interleukin-1beta production.
AB  - BACKGROUND: The involvement of inflammasome activation and macrophage
      polarization during the process of syphilis infection remains unknown. In this
      study, A series of experiments were performed using human macrophages to research
      the role of NLRP3 inflammasome regulation in interleukin (IL)-1beta production
      and its influence on macrophage polarization triggered by T. pallidum. RESULTS:
      The results showed that in M0 macrophages treated with T. pallidum, the M1
      associated markers inducible nitric oxide synthase (iNOS), IL-1beta and TNF-alpha
      were upregulated, and the M2-associated markers CD206 and IL-10 were
      downregulated. In addition, we observed NLRP3 inflammasome activation and IL
      1beta secretion in T. pallidum-treated macrophages, and the observed production
      of IL-1beta occurred in a dose- and time-dependent manner. Moreover, the
      secretion of IL-1beta by macrophages after T. pallidum treatment was notably
      reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and
      CA074-ME treatment also suppressed IL-1beta release from T. pallidum-treated
      macrophages. CONCLUSIONS: These findings showed that T. pallidum induces M0
      macrophages to undergo M1 macrophage polarization and elevate IL-1beta secretion
      through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL
      1beta production in macrophages in response to T. pallidum infection involves K+
      efflux, mitochondrial ROS production and cathepsin release. This study provides a
      new insight into the innate immune response to T. pallidum infection.

PMID- 30217147
TI  - Cryptic sequence features in the active postmortem transcriptome.
AB  - BACKGROUND: Our previous study found that more than 500 transcripts significantly
      increased in abundance in the zebrafish and mouse several hours to days
      postmortem relative to live controls. The current literature suggests that most
      mRNAs are post-transcriptionally regulated in stressful conditions. We
      rationalized that the postmortem transcripts must contain sequence features (3-
      to 9- mers) that are unique from those in the rest of the transcriptome and that
      these features putatively serve as binding sites for proteins and/or non-coding
      RNAs involved in post-transcriptional regulation. RESULTS: We identified 5117 and
      2245 over-represented sequence features in the mouse and zebrafish, respectively,
      which represents less than 1.5% of all possible features. Some of these features
      were disproportionately distributed along the transcripts with high densities in
      the 3' untranslated regions of the zebrafish (0.3 mers/nt) and the open reading
      frames of the mouse (0.6 mers/nt). Yet, the highest density (2.3 mers/nt)
      occurred in the open reading frames of 11 mouse transcripts that lacked 3' or 5'
      untranslated regions. These results suggest the transcripts with high density of
      features might serve as 'molecular sponges' that sequester RNA binding proteins
      and/or microRNAs, and thus indirectly increase the stability and gene expression
      of other transcripts. In addition, some of the features were identified as
      binding sites for Rbfox and Hud proteins that are also involved in increasing
      transcript stability and gene expression. CONCLUSIONS: Our results are consistent
      with the hypothesis that transcripts involved in responding to extreme stress,
      such as organismal death, have sequence features that make them different from
      the rest of the transcriptome. Some of these features serve as putative binding
      sites for proteins and non-coding RNAs that determine transcript stability and
      fate. A small number of the transcripts have high density sequence features,
      which are presumably involved in sequestering RNA binding proteins and microRNAs
      and thus preventing regulatory interactions among other transcripts. Our results
      provide baseline data on post-transcriptional regulation in stressful conditions
      that has implications for regulation in disease, starvation, and cancer.

PMID- 30217148
TI  - Using controls to limit false discovery in the era of big data.
AB  - BACKGROUND: Procedures for controlling the false discovery rate (FDR) are widely
      applied as a solution to the multiple comparisons problem of high-dimensional
      statistics. Current FDR-controlling procedures require accurately calculated p
      values and rely on extrapolation into the unknown and unobserved tails of the
      null distribution. Both of these intermediate steps are challenging and can
      compromise the reliability of the results. RESULTS: We present a general method
      for controlling the FDR that capitalizes on the large amount of control data
      often found in big data studies to avoid these frequently problematic
      intermediate steps. The method utilizes control data to empirically construct the
      distribution of the test statistic under the null hypothesis and directly
      compares this distribution to the empirical distribution of the test data. By not
      relying on p-values, our control data-based empirical FDR procedure more closely
      follows the foundational principles of the scientific method: that inference is
      drawn by comparing test data to control data. The method is demonstrated through
      application to a problem in structural genomics. CONCLUSIONS: The method
      described here provides a general statistical framework for controlling the FDR
      that is specifically tailored for the big data setting. By relying on empirically
      constructed distributions and control data, it forgoes potentially problematic
      modeling steps and extrapolation into the unknown tails of the null distribution.
      This procedure is broadly applicable insofar as controlled experiments or
      internal negative controls are available, as is increasingly common in the big
      data setting.

PMID- 30217150
TI  - Effects of transcranial focused ultrasound on human primary motor cortex using 7T
      fMRI: a pilot study.
AB  - BACKGROUND: Transcranial focused ultrasound (tFUS) is a new non-invasive
      neuromodulation technique that uses mechanical energy to modulate neuronal
      excitability with high spatial precision. tFUS has been shown to be capable of
      modulating EEG brain activity in humans that is spatially restricted, and here,
      we use 7T MRI to extend these findings. We test the effect of tFUS on 7T BOLD
      fMRI signals from individual finger representations in the human primary motor
      cortex (M1) and connected cortical motor regions. Participants (N = 5) performed
      a cued finger tapping task in a 7T MRI scanner with their thumb, index, and
      middle fingers to produce a BOLD signal for individual M1 finger representations
      during either tFUS or sham neuromodulation to the thumb representation. RESULTS:
      Results demonstrated a statistically significant increase in activation volume of
      the M1 thumb representation for the tFUS condition as compared to sham. No
      differences in percent BOLD changes were found. This effect was spatially
      confined as the index and middle finger M1 finger representations did not show
      similar significant changes in either percent change or activation volume. No
      effects were seen during tFUS to M1 in the supplementary motor area or the dorsal
      premotor cortex. CONCLUSIONS: Single element tFUS can be paired with high field
      MRI that does not induce significant artifact. tFUS increases activation volumes
      of the targeted finger representation that is spatially restricted within M1 but
      does not extend to functionally connected motor regions. Trial registration
      ClinicalTrials.gov NCT03634631 08/14/18.

PMID- 30217149
TI  - Pseudomonas aeruginosa responds to exogenous polyunsaturated fatty acids (PUFAs)
      by modifying phospholipid composition, membrane permeability, and phenotypes
      associated with virulence.
AB  - BACKGROUND: Pseudomonas aeruginosa, a common opportunistic pathogen, is known to
      cause infections in a variety of compromised human tissues. An emerging mechanism
      for microbial survival is the incorporation of exogenous fatty acids to alter the
      cell's membrane phospholipid profile. With these findings, we show that exogenous
      fatty acid exposure leads to changes in bacterial membrane phospholipid
      structure, membrane permeability, virulence phenotypes and consequent stress
      responses that may influence survival and persistence of Pseudomonas aeruginosa.
      RESULTS: Thin-layer chromatography and ultra performance liquid chromatography /
      ESI-mass spectrometry indicated alteration of bacterial phospholipid profiles
      following growth in the presence of polyunsaturated fatty acids (PUFAs) (ranging
      in carbon length and unsaturation). The exogenously supplied fatty acids were
      incorporated into the major bacterial phospholipids phosphatidylethanolamine and
      phosphatidylglycerol. The incorporation of fatty acids increased membrane
      permeability as judged by both accumulation and exclusion of ethidium bromide.
      Individual fatty acids were identified as modifying resistance to the cyclic
      peptide antibiotics polymyxin B and colistin, but not the beta-lactam imipenem.
      Biofilm formation was increased by several PUFAs and significant fluctuations in
      swimming motility were observed. CONCLUSIONS: Our results emphasize the relevance
      and complexity of exogenous fatty acids in the membrane physiology and
      pathobiology of a medically important pathogen. P. aeruginosa exhibits
      versatility with regard to utilization of and response to exogenous fatty acids,
      perhaps revealing potential strategies for prevention and control of infection.

PMID- 30217151
TI  - Differences in healthcare costs in youths with conduct disorders in rural vs.
      urban regions: an analysis of German health insurance data.
AB  - BACKGROUND: For children and adolescents with mental health problems, there is a
      lack of data as to whether the type of residential area (urban vs. rural)
      influences healthcare costs for affected individuals. The aim of this study was
      therefore to explore potential urban vs. rural healthcare cost differences in
      children and adolescents with conduct disorder (CD), one of the most frequent and
      cost-intensive child and adolescent psychiatric disorders. Additionally, we aimed
      to compare healthcare costs of youths with CD, and of youths without this
      diagnosis. METHODS: We analysed data from a German health insurance company,
      extracting all youths with a CD diagnosis in 2011 (CD group; N = 6337), and an
      age- and sex-matched group without this diagnosis (control group). For both
      groups, annual costs per person for outpatient and inpatient healthcare were
      aggregated, stratified by area of residence (urban vs. rural). RESULTS: While
      mean annual overall costs in the CD group did not differ significantly between
      urban and rural areas of residence (2785 EUR vs. 3557 EUR, p = 0.253), inpatient
      treatment costs were significantly higher in rural areas (2166 EUR (60.9% of
      overall costs) vs. 1199 EUR (43.1% of overall costs), p < 0.0005). For outpatient
      healthcare costs, the reverse effect was found, with significantly higher costs
      in individuals from urban areas of residence (901 EUR (32.3% of overall costs)
      vs. 581 EUR (16.3% of overall costs), p < 0.0005). In the control group, no
      significant rural vs. urban difference was found for either overall health costs,
      inpatient or outpatient costs. Mean overall costs in the CD group were four times
      higher than in the control group (3162 (+/-5934) EUR vs. 795 (+/-4425) EUR).
      CONCLUSIONS: This study is the first to demonstrate urban vs. rural differences
      in healthcare costs among youths with CD. The higher costs of inpatient treatment
      in rural regions may indicate a need for alternative forms of service provision
      and delivery in rural settings.

PMID- 30217152
TI  - Improving management of tuberculosis in people living with HIV in South Africa
      through integration of HIV and tuberculosis services: a proof of concept study.
AB  - BACKGROUND: South Africa's tuberculosis burden is the third highest globally and
      is closely associated with the country's devastating HIV epidemic. The separation
      of HIV and TB services in primary healthcare services in South Africa hampers TB
      case finding in patients who are co-infected with HIV and TB. This operational
      proof of concept study assessed an approach to improving tuberculosis detection
      and treatment by integrating tuberculosis management into HIV care. METHODS: The
      intervention involved workforce re-engineering accompanied by changes to the
      physical environment in three primary healthcare facilities in Gert Sibande
      district, Mpumalanga Province, that allowed HIV providers to test their HIV
      patients for TB and initiate and monitor TB treatment when indicated. To assess
      the proof of concept we compared the management of TB patients by HIV and TB
      providers, by reviewing the records of all facility patients who tested positive
      for tuberculosis between July 2015 and February 2016. We also considered the
      perceptions of healthcare providers and facility managers about the intervention
      through structured interviews. RESULTS: Approximately 30% of the 1855 patients
      with presumed TB in the three clinics had been identified by HIV providers. The
      percentage of patients consecutively tested for TB was 81.0% and 85.0% (p =
      0.0551) for HIV and TB providers, respectively. Of the patients identified with
      TB by HIV and TB providers, 75.4% and 79.2% (p = 0.2876), respectively, were
      initiated on treatment. The defaulter rate was higher among HIV, compared to TB,
      providers (12.8% versus 4.2%). Overall, healthcare providers and facility
      managers had positive views of the intervention but raised concerns regarding
      potential increase in workload and administrative issues, as well as infection
      control. CONCLUSIONS: The results of this proof-of-concept study indicate that
      the full spectrum of TB services can be easily and effectively integrated into
      existing HIV care programs. However, a possible shift in the service providers'
      workload, including administrative tasks, must be tackled and effective infection
      control must be ensured. Further research is needed to assess the impact of TB
      service integration into the scope of HIV care (or other chronic care programs)
      on patient outcomes, including analysis of routine data.

PMID- 30217153
TI  - Sexual and reproductive healthcare for women asylum seekers in Switzerland: a
      multi-method evaluation.
AB  - BACKGROUND: Forced migration significantly endangers health. Women face numerous
      health risks, including sexual violence, lack of contraception, sexually
      transmitted disease, and adverse perinatal outcomes. Therefore, sexual and
      reproductive healthcare is a significant aspect of women asylum seekers' health.
      Even when healthcare costs of asylum seekers are covered by the government, there
      may be strong barriers to healthcare access and specific needs may be addressed
      inadequately. The study's objectives were a) to assess the accommodation and
      healthcare services provided to women asylum seekers in standard and specialised
      health care, b) to assess the organisation of healthcare provision and how it
      addresses the sexual and reproductive healthcare needs of women asylum seekers.
      METHODS: The study utilised a multi-method approach, comprising a less-dominant
      quantitative component and dominant qualitative component. The quantitative
      component assessed accommodation conditions for women in eight asylum centres
      using a survey. The qualitative component assessed healthcare provision on-site,
      using semi-structured interviews with health and social care professionals (n =
      9). Asylum centres were selected to cover a wide range of characteristics.
      Interview analysis was guided by thematic analysis. RESULTS: The accommodation in
      the asylum centres provided gender-separate rooms and sanitary infrastructure.
      Two models of healthcare were identified, which differed in the services they
      provided and in their organisation: 1) a standard healthcare model characterised
      by a lack of coordination between healthcare providers, unavailability of
      essential services such as interpreters, and fragmented healthcare, and 2) a
      specialised healthcare model specifically tailored to the needs of asylum
      seekers. Its organisation is characterised by a network of closely collaborating
      health professionals. It provided essential services not present in the standard
      model. We recommend the specialised healthcare model as a guideline for best
      practise. CONCLUSIONS: The standard, non-specialised healthcare model used in
      some regions in Switzerland does not fully meet the healthcare needs of women
      asylum seekers. Specialised healthcare services used in other regions, which
      include translation services as well as gender and culturally sensitive care, are
      better suited to address these needs. More widespread use of this model would
      contribute significantly toward protecting the sexual and reproductive integrity
      and health of women asylum seekers.

PMID- 30217154
TI  - Estrogen receptor 1 gene polymorphisms are associated with metabolic syndrome in
      postmenopausal women in China.
AB  - BACKGROUND: Metabolic syndrome (MetS) includes obesity, diabetes, dyslipidemia
      and hypertension. Its incidence is rapidly increasing worldwide, particularly in
      postmenopausal women. Estrogens regulate glucose homeostasis and lipid metabolism
      via estrogen receptors 1 (ESR1) and 2 (ESR2). The current study aimed to
      elucidate associations of MetS with ESR1 and ESR2 gene polymorphisms in
      postmenopausal Chinese women. METHODS: This case-control study included 304
      postmenopausal women (154 and 150 control and MetS patients, respectively).
      Clinical indicators related to MetS were assessed. Two ESR1 (PvuII and XbaI) and
      two ESR2 (RsaI and AluI) polymorphisms were evaluated by polymerase chain
      reaction (PCR)-restriction fragment length polymorphism analysis. RESULTS: ESR1
      polymorphisms were significantly different between MetS patients and healthy
      controls. G allele frequency for the XbaI polymorphism was significantly higher
      in patients than in control patients (p = 0.004, OR = 1.610, 95%CI 1.169-2.18).
      The haplotypes A-T (p = 0.015) and G-C (p = 0.024) showed significant
      differences. The minor alleles of the XbaI and PvuII gene polymorphisms in both
      homozygous and heterozygous forms showed associations with elevated waist
      circumference, fasting serum insulin and HOMA-IR. The minor G allele in
      homozygous and heterozygous forms of the RsaI and AluI gene polymorphisms showed
      associations with elevated total cholesterol and LDL-C. CONCLUSIONS: In
      postmenopausal Chinese women, ESR1 polymorphism and the haplotypes A-T and G-C of
      XbaI-PvuII are associated with MetS, unlike ESR2 polymorphisms. Patients
      harboring the G allele of XbaI have elevated BMI, waist circumference, systolic
      and diastolic BP, FBG, HOMA-IR, total cholesterol, TG, LDL-C and NAFLD (%), and
      reduced HDL-C.

PMID- 30217155
TI  - Factors associated with unplanned readmissions within 1 day of acute care
      discharge: a retrospective cohort study.
AB  - BACKGROUND: Unplanned hospital readmissions are a quality and safety indicator.
      In Australian, 8% to 11.1% of unplanned readmissions occur <=1 day of acute care
      discharge. The aim of this study was to explore the reasons for unplanned
      hospital readmissions <=1 day of acute care discharge, and determine what
      proportion of such unplanned hospital readmissions were potentially preventable.
      METHODS: A retrospective exploratory cohort design was used to conduct this two
      phase study. In Phase 1, organisational data from 170 readmissions <=1 day and
      1358 readmissions between 2 and 28 days were compared using the Cochran-Mantel
      Haenszel test. Binary logistic regression was used to examine factors associated
      with unplanned readmission <=1 day. In Phase 2, a medical record audit of 162
      Phase 1 readmissions <=1 day was conducted and descriptive statistics used to
      summarise the study data. Index discharges occurred between 1 August and 31
      December 2015. RESULTS: In Phase 1, unplanned readmissions <=1 day were more
      likely in paediatric patients (< 0.001); index discharges on weekends (p =
      0.006), from short stay unit (SSU) (p < 0.001) or against health professional
      advice (p = 0.010); or when the readmission was for a Diagnosis Related Group (p
      < 0.001). The significant predictors of unplanned readmission <=1 day were index
      discharge against advice or from SSU, and 1-5 hospital admissions in the 6 months
      preceding index admission. In Phase 2, 88.3% readmissions were unpreventable and
      11.7% were preventable. The median patient age was 57 years and comorbidities
      were uncommon (3.1%). Most patients (94.4%) lived at home and with others
      (78.9%). Friday was the most common day of index discharge (17.3%) and Saturday
      was the most common day of unplanned readmission (19.1%). The majority (94.4%) of
      readmissions were via the emergency department: 58.5% were for a like diagnosis
      and pain was the most common reason for readmission. CONCLUSIONS: Advanced age,
      significant comorbidities and social isolation did not feature in patients with
      an unplanned readmission <=1 day. One quarter of patients were discharged on a
      Friday or weekend, one quarter of readmissions occurred on a weekend, and pain
      was the most common reason for readmission raising issues about access to
      services and weekend discharge planning.

PMID- 30217156
TI  - Trends in healthcare utilization and costs associated with pneumonia in the
      United States during 2008-2014.
AB  - BACKGROUND: Pneumonia is the leading cause of morbidity and mortality worldwide.
      Pneumococcal conjugate vaccines have reduced the burden of pneumonia, but data on
      the current burden of pneumonia and its impact on the healthcare system are
      needed to inform the development and use of new vaccines and other preventive
      measures. METHODS: We retrospectively analyzed the frequency of pneumonia in the
      US during 2008-2014 using data from the MarketScan(r) Commercial Claims and
      Encounters database. Frequencies of healthcare utilization related to the index
      pneumonia episode were calculated using the annual number of enrolled person
      years (PY) as the denominator and the number of individuals with pneumonia as the
      numerator. Pneumonia-associated costs were calculated as mean payment per episode
      during the 2 years from 2013 to 2014. RESULTS: The overall annual healthcare
      utilization rate for pneumonia was 15.1 per 1000 PY and decreased slightly from
      2008 to 2014 (from 15.4 to 13.5 per 1000 PY). Most pneumonia-related healthcare
      utilization was due to office/outpatient visits (10.3 per 1000 PY; 68.3%).
      Emergency department/urgent care visits (2.5 per 1000 PY; 16.9%) and
      hospitalizations (2.2 per 1000 PY; 14.8%) contributed less. Pneumonia-related
      healthcare utilization was highest in children < 5 years (rate per 1000 PY = 29.7
      for < 1 year, 47.9 for 1 year, and 39.5 for 2-4 years) and adults > 65 years
      (45.0 per 1000 PY). The mean cost per pneumonia episode (95% confidence interval)
      was US$429.1 ($424.8-$433.4) for office/outpatient visits, $1126.9 ($1119.5
      $1134.3) for emergency department/urgent care visits, and $10,962.5 ($10,822.8
      $11,102.2) for hospitalization. CONCLUSIONS: The burden of pneumonia on the US
      healthcare system remains substantial. The results presented here can help guide
      new vaccination strategies and other preventive interventions for reducing the
      remaining burden of pneumonia.

PMID- 30217157
TI  - Evidence-based practice profiles among bachelor students in four health
      disciplines: a cross-sectional study.
AB  - BACKGROUND: Despite the recognition of integrating evidence-based practice (EBP)
      in educational programs, there is limited research about bachelor students' EBP
      profiles (EBP knowledge, attitudes and behaviour) in the health disciplines
      nursing, occupational therapy, physiotherapy and radiography. The aim of this
      study was to assess EBP profiles among bachelor students in health disciplines,
      and explore differences between health disciplines, educational institutions,
      students' assessment of EBP teaching and expectations of EBP performance.
      METHODS: A survey using the 'Evidence-Based Practice Profile - Norwegian version'
      (EBP2-N) was conducted among final year bachelor students in health disciplines
      from four educational institutions. The questionnaire consisted of five domains
      (Relevance, Terminology, Confidence, Practice and Sympathy) and assessed the five
      steps of EBP. We performed regression analyses to analyse mean differences in
      domain scores between health disciplines, Cohen's d to illustrate the magnitude
      of the largest difference in each domain, Omega squared to describe portion of
      variance in domain scores, and Spearman's rho (rs) to assess the monotonic
      relationship between EBP2-N domains and assessment of EBP teaching and
      expectations of EBP performance, respectively. RESULTS: Students reported highest
      overall mean score for Relevance, with an estimated standardized mean of 81.2 (CI
      95% = 80.4-82.0). The other EBP2-N domains had estimated standardized means of 54
      and less. Statistically significant differences (p < 0.03) between health
      disciplines were observed for all domains. The largest mean difference was found
      for Relevance with highest score for occupational therapy and lowest for
      radiography, with an estimated Cohen's d of 1.11. Moderate positive associations
      were observed between Relevance scores and students' assessment of EBP teaching
      (rs = 0.31), and expectations of EBP performance from teachers (rs = 0.36). We
      also observed a moderate positive correlation between Confidence and students'
      assessment of EBP teaching (rs = 0.46). CONCLUSION: Bachelor students in health
      disciplines found EBP relevant, but revealed low understanding of EBP
      terminology, low confidence with EBP skills, and low use of EBP in clinical
      situations. We observed differences in EBP profiles between health disciplines
      and between educational institutions. The differences in scores raise questions
      about the understanding of EBP within disciplines, and the complexity of EBP in
      educational settings.

PMID- 30217158
TI  - Fungal infection has sublethal effects in a lowland subtropical amphibian
      population.
AB  - BACKGROUND: The amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd),
      has been implicated as a primary cause of decline in many species around the
      globe. However, there are some species and populations that are known to become
      infected in the wild, yet declines have not been observed. Here we conducted a
      yearlong capture-mark-recapture study and a 2-year long disease monitoring study
      of northern cricket frogs, Acris crepitans, in the lowland subtropical forests of
      Louisiana. RESULTS: We found little evidence for an impact of Bd infection on
      survival; however, Bd infection did appear to cause sublethal effects, including
      increased capture probability in the field. CONCLUSIONS: Our study suggests that
      even in apparently stable populations, where Bd does not appear to cause
      mortality, there may be sublethal effects of infection that can impact a host
      population's dynamics and structure. Understanding and documenting such sublethal
      effects of infection on wild, seemingly stable populations is important,
      particularly for predicting future population declines.

PMID- 30217159
TI  - Traditional knowledge regarding edible insects in Burkina Faso.
AB  - BACKGROUND: Insects play an important role as a diet supplement in Burkina Faso,
      but the preferred insect species vary according to the phytogeographical zone,
      ethnic groups, and gender. The present study aims at documenting indigenous
      knowledge on edible insects in Burkina Faso. METHODS: A structured ethno
      sociological survey was conducted with 360 informants in nine villages located in
      two phytogeographical zones of Burkina Faso. Identification of the insects was
      done according to the classification of Scholtz. Chi-square tests and principal
      component analysis were performed to test for significant differences in edible
      insect species preferences among phytogeographical zones, villages, ethnic
      groups, and gender. RESULTS: Edible insects were available at different times of
      the year. They were collected by hand picking, digging in the soil, and luring
      them into water traps. The edible insects collected were consumed fried, roasted,
      or grilled. All species were indifferently consumed by children, women, and men
      without regard to their ages. A total of seven edible insect species belonging to
      five orders were cited in the Sudanian zone of Burkina Faso. Macrotermes
      subhyalinus (Rambur), Cirina butyrospermi (Vuillet, 1911), Kraussaria angulifera
      (Krauss, 1877), Gryllus campestris (Linnaeus, 1758), and Carbula marginella
      (Thunberg) (35.66-8.47% of the citations) were most cited whereas Rhynchophorus
      phoenicis (Fabricius, 1801) and Oryctes sp. (3.41-0.27%) were least cited. Cirina
      butyrospermi was most cited in the South Sudanian zone, whereas Macrotermes
      subhyalinus and Kraussaria angulifera were most cited in the North Sudanian zone
      but were cited in all nine villages. Cirina butyrospermi was preferred by Bobo,
      Guin, Sambla, Senoufo, and Turka ethnic groups whereas Macrotermes subhyalinus
      was preferred by Fulani, Mossi, and Toussian ethnic groups. Oryctes sp. was cited
      only by the Toussian. CONCLUSION: A diversity of edible insects was consumed in
      both the South and North Sudanian zone of Burkina Faso with significant
      differences in species preferences according to phytogeographical zones,
      villages, ethnic groups, and gender.

PMID- 30217160
TI  - Development of a PMMA phantom as a practical alternative for quality control of
      gamma knife(r) dosimetry.
AB  - BACKGROUND: To measure the absorbed dose rate to water and penumbra of a Gamma
      Knife(r) (GK) using a polymethyl metacrylate (PMMA) phantom. METHODS: A multi
      purpose PMMA phantom was developed to measure the absorbed dose rate to water and
      the dose distribution of a GK. The phantom consists of a hemispherical outer
      phantom, one exchangeable cylindrical chamber-hosting inner phantom, and two film
      hosting inner phantoms. The radius of the phantom was determined considering the
      electron density of the PMMA such that it corresponds to 8 g/cm2 water depth,
      which is the reference depth of the absorbed dose measurement of GK. The absorbed
      dose rate to water was measured with a PTW TN31010 chamber, and the dose
      distributions were measured with radiochromic films at the calibration center of
      a patient positioning system of a GK Perfexion. A spherical water-filled phantom
      with the same water equivalent depth was constructed as a reference phantom. The
      dose rate to water and dose distributions at the center of a circular field
      delimited by a 16-mm collimator were measured with the PMMA phantom at six GK
      Perfexion sites. RESULTS: The radius of the PMMA phantom was determined to be
      6.93 cm, corresponding to equivalent water depth of 8 g/cm2. The absorbed dose
      rate to water was measured with the PMMA phantom, the spherical water-filled
      phantom and a commercial solid water phantom. The measured dose rate with the
      PMMA phantom was 1.2% and 1.8% higher than those measured with the spherical
      water-filled phantom and the solid water phantom, respectively. These differences
      can be explained by the scattered photon contribution of PMMA off incoming 60Co
      gamma-rays to the dose rate. The average full width half maximum and penumbra
      values measured with the PMMA phantom showed reasonable agreement with two
      calculated values, one at the center of the PMMA phantom (LGP6.93) and other at
      the center of a water sphere with a radius of 8 cm (LGP8.0) given by Leksell
      Gamma Plan using the TMR10 algorithm. CONCLUSIONS: A PMMA phantom constructed in
      this study to measure the absorbed dose rates to water and dose distributions of
      a GK represents an acceptable and practical alternative for GK dosimetry
      considering its cost-effectiveness and ease of handling.

PMID- 30217161
TI  - Immunization with a suicidal DNA vaccine expressing the E glycoprotein protects
      ducklings against duck Tembusu virus.
AB  - BACKGROUD: Duck Tembusu virus (DTMUV), a pathogenic flavivirus, emerged in China
      since 2010 and causing huge economic loss in the Chinese poultry industry.
      Although several vaccines have been reported to control DTMUV disease, few
      effective vaccines are available and new outbreaks were continuously reported.
      Thus, it is urgently to develop a new effective vaccine for prevention of this
      disease. METHODS: In this study, a suicidal DNA vaccine based on a Semliki Forest
      virus (SFV) replicon and DTMUV E glycoprotein gene was constructed and the
      efficacy of this new vaccine was assessed according to humoral and cell-mediated
      immune responses as well as protection against the DTMUV challenge in ducklings.
      RESULTS: Our results showed that the recombinant SFV replicon highly expressed E
      glycoprotein in DEF cells. After intramuscular injection of this new DNA vaccine
      in ducklings, robust humoral and cellular immune responses were observed in all
      immunized ducklings. Moreover, all ducklings were protected against challenge
      with the virulent DTMUV AH-F10 strain. CONCLUSIONS: In conclusion, we demonstrate
      that this suicidal DNA vaccine is a promising candidate facilitating the
      prevention of DTMUV infection.

PMID- 30217162
TI  - Intraventricular infusion of quinolinic acid impairs spatial learning and memory
      in young rats: a novel mechanism of lead-induced neurotoxicity.
AB  - BACKGROUND: Lead (Pb), a heavy metal, and quinolinic acid (QA), a metabolite of
      the kynurenine pathway of tryptophan metabolism, are known neurotoxicants. Both
      Pb and QA impair spatial learning and memory. Pb activates astrocytes and
      microglia, which in turn induce the synthesis of QA. We hypothesized increased QA
      production in response to Pb exposure as a novel mechanism of Pb-neurotoxicity.
      METHODS: Two experimental paradigms were used. In experiment one, Wistar rat pups
      were exposed to Pb via their dams' drinking water from postnatal day 1 to 21.
      Control group was given regular water. In the second protocol, QA (9 mM) or
      normal saline (as Vehicle Control) was infused into right lateral ventricle of 21
      day old rats for 7 days using osmotic pumps. Learning and memory were assessed by
      Morris water maze test on postnatal day 30 or 45 in both Pb- and QA-exposed rats.
      QA levels in the Pb exposed rats were measured in blood by ELISA and in the brain
      by immunohistochemistry on postnatal days 45 and 60. Expression of various
      molecules involved in learning and memory was analyzed by Western blot. Means of
      control and experimental groups were compared with two-way repeated measure ANOVA
      (learning) and t test (all other variables). RESULTS: Pb exposure increased QA
      level in the blood (by ~ 58%) and increased (p < 0.05) the number of QA
      immunoreactive cells in the cortex, and CA1, CA3 and dentate gyrus regions of the
      hippocampus, compared to control rats. In separate experiments, QA infusion
      impaired learning and short-term memory similar to Pb. PSD-95, PP1, and PP2A were
      decreased (p < 0.05) in the QA-infused rats, whereas tau phosphorylation was
      increased, compared to vehicle infused rats. CONCLUSION: Putting together the
      results of the two experimental paradigms, we propose that increased QA
      production in response to Pb exposure is a novel mechanism of Pb-induced
      neurotoxicity.

PMID- 30217163
TI  - Reliability of the gamma index analysis as a verification method of volumetric
      modulated arc therapy plans.
AB  - BACKGROUND: We investigate the gamma passing rate (GPR) consistency when applying
      different types of gamma analyses, linacs, and dosimeters for volumetric
      modulated arc therapy (VMAT). METHODS: A total of 240 VMAT plans for various
      treatment sites, which were generated with Trilogy (140 plans) and TrueBeam STx
      (100 plans), were retrospectively selected. For each VMAT plan, planar dose
      distributions were measured with both MapCHECK2 and ArcCHECK dosimeters. During
      the planar dose distribution measurements, the actual multileaf collimator (MLC)
      positions, gantry angles, and delivered monitor units were recorded and compared
      to the values in the original VMAT plans to calculate mechanical errors. For each
      VMAT plan, both the global and local gamma analyses were performed with 3%/3 mm,
      2%/2 mm, 2%/1 mm, 1%/2 mm, and 1%/1 mm. The Pearson correlation coefficients (r)
      were calculated 1) between the global and the local GPRs, 2) between GPRs with
      the MapCHECK2 and the ArcCHECK dosimeters, 3) and between GPRs and the mechanical
      errors during the VMAT delivery. RESULTS: For the MapCHECK2 measurements, strong
      correlations between the global and local GPRs were observed only with 1%/2 mm
      and 1%/1 mm (r > 0.8 with p < 0.001), while weak or no correlations were observed
      for the ArcCHECK measurement. Between the MapCHECK2 and ArcCHECK measurements,
      the global GPRs showed no correlations (all with p > 0.05), while the local GPRs
      showed moderate correlations only with 2%/1 mm and 1%/1 mm for TrueBeam STx (r >
      0.5 with p < 0.001). Both the global and local GPRs always showed weak or no
      correlations with the MLC positional errors except for the GPRs of MapCHECK2 with
      1%/2 mm and 1%/1 mm for TrueBeam STx and the GPR of ArcCHECK with 1%/2 mm for
      Trilogy (r < - 0.5 with p < 0.001). CONCLUSIONS: The GPRs varied according to the
      types of gamma analyses, dosimeters, and linacs. Therefore, each institution
      should carefully establish their own gamma analysis protocol by determining the
      type of gamma index analysis and the gamma criterion with their own linac and
      their own dosimeter.

PMID- 30217164
TI  - Effect of PEA-OXA on neuropathic pain and functional recovery after sciatic nerve
      crush.
AB  - BACKGROUND: Animal models of sciatic nerve injury are commonly used to study
      neuropathic pain as well as axon regeneration. Inflammation/immune response at
      the site of nerve lesion is known to be an essential trigger of the pathological
      changes that have a critical impact on nerve repair and regeneration; moreover,
      the damage to peripheral nerve can cause a loss of sensory function and produces
      a persistent neuropathic pain. N-Acylethanolamines (NAEs) involve a family of
      lipid molecules existent in animal and plant, of which is N-palmitoylethanolamide
      (PEA) that arouses great attention owing to its anti-inflammatory, analgesic, and
      neuroprotective activities. The modulation of specific amidases for NAEs (and in
      particular NAE-hydrolyzing acid amidase NAAA, which is more selective for PEA)
      could be a condition to preserve its levels. Here, we investigated, in a mice
      model of sciatic nerve crush, the effect of 2-pentadecyl-2-oxazoline (PEA-OXA)
      the oxazoline of PEA that reportedly modulates activity of NAAA. METHODS: In this
      experimental model, the mice, following the sciatic nerve crush, were treated
      daily with PEA-OXA at a dose of 10 mg?kg for 14 days. Therefore, we evaluated the
      effects of PEA-OXA on the degree of injury, on the inhibition of neuropathic
      pain, and on the inflammatory process, as in the improvement of reparative
      processes and therefore in the restoration of locomotor function. RESULTS: Our
      results showed that PEA-OXA (10 mg/kg) treatment, daily, for 14 days after
      sciatic nerve crush, have an anti-inflammatory and neuroprotective effect and
      moreover have an analgesic protective effect on hypersensitivity, and improve the
      functional recovery after nerve crush. CONCLUSIONS: Therefore, treatment with PEA
      OXA as a whole has shown a protective effect, which makes it a powerful candidate
      for the treatment of peripheral nerve injury and neuropathic pain.

PMID- 30217165
TI  - Intensity-modulated radiation therapy for definitive treatment of cervical
      cancer: a meta-analysis.
AB  - BACKGROUND: To compare the efficacies and toxicities of intensity-modulated
      radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT) or
      conventional two-dimensional radiotherapy (2D-RT) for definitive treatment of
      cervical cancer. METHODS: A meta-analysis was performed using search engines,
      including PubMed, Cochrane Library, Web of Science, and Elsevier. In the meta
      analysis, odds ratios (ORs) were compared for overall survival (OS), disease-free
      survival (DFS), and acute and chronic toxicities. RESULTS: Included data were
      analysed using RevMan 5.2 software. Six studies encompassing a total of 1008
      patients who received definitive treatment (IMRT = 350, 3-DCRT/2D-RT = 658) were
      included in the analysis. A comparison of 3-year OS and 3-year DFS revealed no
      significant differences between IMRT and 3D-CRT or 2D-RT (3-year OS: OR = 2.41,
      95% confidence interval [CI]: 0.62-9.39, p = 0.21; 3-year DFS: OR = 1.44, 95% CI:
      0.69-3.01, p = 0.33). The incidence of acute gastrointestinal (GI) toxicity and
      genitourinary (GU) toxicity in patients who received IMRT was significantly lower
      than that in the control group (GI: Grade 2: OR = 0.5, 95% CI: 0.28-0.89, p =
      0.02; Grade 3 or higher: OR = 0.55, 95% CI: 0.32-0.95, p = 0.03; GU: Grade 2: OR
      = 0.41, 95% CI: 0.2-0.84; p = 0.01; Grade 3 or higher: OR = 0.31, 95% CI: 0.14
      0.67, p = 0.003). Moreover, the IMRT patients experienced fewer incidences of
      chronic GU toxicity than did the control group (Grade 3: OR = 0.09, 95% CI: 0.01
      0.67, p = 0.02). CONCLUSION: IMRT and conventional radiotherapy demonstrated
      equivalent efficacy in terms of 3-year OS and DFS. Additionally, IMRT
      significantly reduced acute GI and GU toxicities as well as chronic GU toxicity
      in patients with cervical cancer.

PMID- 30217166
TI  - Exome sequencing study in patients with multiple sclerosis reveals variants
      associated with disease course.
AB  - BACKGROUND: It remains unclear whether disease course in multiple sclerosis (MS)
      is influenced by genetic polymorphisms. Here, we aimed to identify genetic
      variants associated with benign and aggressive disease courses in MS patients.
      METHODS: MS patients were classified into benign and aggressive phenotypes
      according to clinical criteria. We performed exome sequencing in a discovery
      cohort, which included 20 MS patients, 10 with benign and 10 with aggressive
      disease course, and genotyping in 2 independent validation cohorts. The first
      validation cohort encompassed 194 MS patients, 107 with benign and 87 with
      aggressive phenotypes. The second validation cohort comprised 257 patients, of
      whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain
      immunohistochemistries were performed using disease course associated genes
      antibodies. RESULTS: By means of single-nucleotide polymorphism (SNP) detection
      and comparison of allele frequencies between patients with benign and aggressive
      phenotypes, a total of 16 SNPs were selected for validation from the exome
      sequencing data in the discovery cohort. Meta-analysis of genotyping results in
      two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768,
      significantly associated with disease course. SNP rs28469012 is located in CPXM2
      (carboxypeptidase X, M14 family, member 2) and was associated with aggressive
      disease course (uncorrected p value < 0.05). SNP rs10894768, which is positioned
      in IGSF9B (immunoglobulin superfamily member 9B) was associated with benign
      phenotype (uncorrected p value < 0.05). In addition, a trend for association with
      benign phenotype was observed for a third SNP, rs10423927, in NLRP9 (NLR family
      pyrin domain containing 9). Brain immunohistochemistries in chronic active
      lesions from MS patients revealed expression of IGSF9B in astrocytes and
      macrophages/microglial cells, and expression of CPXM2 and NLRP9 restricted to
      brain macrophages/microglia. CONCLUSIONS: Genetic variants located in CPXM2,
      IGSF9B, and NLRP9 have the potential to modulate disease course in MS patients
      and may be used as disease activity biomarkers to identify patients with
      divergent disease courses. Altogether, the reported results from this study
      support the influence of genetic factors in MS disease course and may help to
      better understand the complex molecular mechanisms underlying disease
      pathogenesis.

PMID- 30217167
TI  - Accuracy of F-18 FDG PET/CT with optimal cut-offs of maximum standardized uptake
      value according to size for diagnosis of regional lymph node metastasis in
      patients with rectal cancer.
AB  - BACKGROUND: The low sensitivity of F-18 fluorodeoxyglucose (FDG) positron
      emission tomography/computed tomography (PET/CT) for the evaluation of metastatic
      lymph nodes (LNs) is mainly due to the partial volume effect in patients with
      rectal cancer. This retrospective study evaluated the diagnostic accuracy of F-18
      FDG PET/CT with optimal cut-off values of the maximum standardized uptake value
      (SUVmax), according to LN size, for the evaluation of regional LN in rectal
      cancer patients. METHODS: This study included 176 patients with rectal cancer who
      underwent F-18 FDG PET/CT for initial staging. Patients were classified based on
      the long-axis diameter of the regional LN on CT images as small (<= 7 mm; n =
      118) and large (> 7 mm; n = 58) LN groups. The optimal cut-off value of SUVmax
      was determined for each group, using receiver operating characteristic curve
      analysis. Areas under the curve (AUC) were compared by C-statistics using two
      methods: the cut-off value of SUVmax optimized according to LN size, and a fixed
      SUVmax cut-off value of 2.5. RESULTS: The optimal cut-off values of SUVmax for
      the small and large LN groups were 1.1, and 2.1, respectively. The sensitivity,
      specificity, and accuracy of F-18 FDG PET/CT using the optimal cut-off values
      were 90.6, 70.9, and 76.3% in the small LN group, and 68.6, 78.3, and 72.4% in
      the large LN group. The sensitivity, specificity, and accuracy of F-18 FDG PET/CT
      using the fixed cut-off value were 18.8, 100, and 78.0% in the small LN group,
      and 51.4, 87.0, and 65.5% in the large LN group. The AUC was significantly higher
      using the optimal cut-off values than the fixed cut-off value (0.808 vs. 0.594, p
      = 0.005) in the small LN group, but not in the large LN group (0.734 vs. 0.692, p
      = 0.429). CONCLUSIONS: Application of the lower cut-off value of SUVmax improves
      the diagnostic performance of F-18 FDG PET/CT for the evaluation of small
      regional LNs in patients with rectal cancer.

PMID- 30217168
TI  - Association between semi-quantitative microbial load and respiratory symptoms
      among Thai military recruits: a prospective cohort study.
AB  - BACKGROUND: Multiplex real-time polymerase chain reaction assays have improved
      diagnostic sensitivity for a wide range of pathogens. However, co-detection of
      multiple agents and bacterial colonization make it difficult to distinguish
      between asymptomatic infection or illness aetiology. We assessed whether semi
      quantitative microbial load data can differentiate between symptomatic and
      asymptomatic states for common respiratory pathogens. METHODS: We obtained throat
      and nasal swab samples from military trainees at two Thai Army barracks.
      Specimens were collected at the start and end of 10-week training periods (non
      acute samples), and from individuals who developed upper respiratory tract
      infection during training (acute samples). We analysed the samples using a
      commercial multiplex respiratory panel comprising 33 bacterial, viral and fungal
      targets. We used random effects tobit models to compare cycle threshold (Ct)
      value distributions from non-acute and acute samples. RESULTS: We analysed 341
      non-acute and 145 acute swab samples from 274 participants. Haemophilus
      influenzae type B was the most commonly detected microbe (77.4% of non-acute and
      64.8% of acute samples). In acute samples, nine specific microbe pairs were
      detected more frequently than expected by chance. Regression models indicated
      significantly lower microbial load in non-acute relative to acute samples for H.
      influenzae non-type B, Streptococcus pneumoniae and rhinovirus, although it was
      not possible to identify a Ct-value threshold indicating causal etiology for any
      of these organisms. CONCLUSIONS: Semi-quantitative measures of microbial
      concentration did not reliably differentiate between illness and asymptomatic
      colonization, suggesting that clinical symptoms may not always be directly
      related to microbial load for common respiratory infections.

PMID- 30217169
TI  - Hepatitis virus (HCV) diagnosis and access to treatment in a UK cohort.
AB  - BACKGROUND: As direct acting antiviral (DAA) therapy is progressively rolled out
      for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV
      epidemiology, diagnostic testing, and access to care is crucial to underpin
      improvements in delivery of treatment, with the ultimate goal of elimination.
      METHODS: We retrospectively studied microbiology records from a large UK teaching
      hospital in order to compare the performance of HCV screening and diagnostic
      tests (antibody, antigen and HCV RNA detection). Having described a local cohort
      of adults with active HCV infection, we investigated the proportion who attended
      hospital appointments, were prescribed direct acting antiviral (DAA) therapy, and
      cleared HCV RNA following treatment. RESULTS: Over a total time period of 33
      months between 2013 and 2016, we tested 38,509 individuals for HCV infection and
      confirmed a new diagnosis of active HCV infection (HCV-Ag + and/or HCV RNA+) in
      353 (positive rate 0.9%). Our in-house HCV-Ab screening test had a positive
      predictive value of 87% compared to repeat HCV-Ab testing in a reference
      laboratory, highlighting the potential for false positives to arise using this
      test. HCV-Ag had 100% positive predictive value compared to detection of HCV RNA.
      There was a strong correlation between quantitative HCV-Ag and HCV RNA viral load
      (p < 0.0001). Among the cases of infection, genotype-1 and genotype-3
      predominated, the median age was 37 years, 84% were male, and 36% were in prison.
      Hepatology review was provided in 39%, and 22% received treatment. Among those
      who received DAA therapy with 12 weeks of follow-up, 93% achieved a sustained
      virologic response (SVR12). CONCLUSIONS: HCV-Ag performs well as a diagnostic
      test compared to PCR for HCV RNA. Active HCV infection is over-represented among
      men and in the prison population. DAA therapy is successful in those who receive
      it, but a minority of patients with a diagnosis of HCV infection access clinical
      care. Enhanced efforts are required to provide linkage to clinical care within
      high risk populations.

PMID- 30217170
TI  - Surgical treatment and perioperative management of intracranial aneurysms in
      Chinese patients with ischemic cerebrovascular diseases: a case series.
AB  - BACKGROUND: Patients with ischemic cerebrovascular diseases are more likely to
      suffer from intracranial aneurysms, and their surgical treatment has a growing
      controversy in this condition. The current case series was aimed at exploring
      surgical treatment and perioperative management of intracranial aneurysms in
      Chinese patients with ischemic cerebrovascular diseases. METHODS: Minimally
      invasive surgical approach through small pterion or inferolateral forehead was
      applied in 31 patients. Anti-platelet drugs were withdrawn 1 week before surgical
      operation. Systolic blood pressure was controlled to be more than 110 mmHg and
      increased by 20% after the clipping of intracranial aneurysms. Branches of
      external carotid artery were spared to ensure collateral circulation. Temporary
      blocking was minimized and ischemic time was shortened during surgical operation.
      RESULTS: Patients had an average age of 66 (46-78) years, and proportion of males
      was 39% (12 males). There were 35 unruptured intracranial aneurysms with a
      diameter more than 5 mm. There were 20 posterior communicating and anterior
      choroidal aneurysms (57%), seveb middle cerebral aneurysms (20%), and eight
      anterior communicating aneurysms (23%), with 21 lobular aneurysms (60%). Twenty
      nine patients had normal neurological function (Glasgow Outcome Scale [GOS] 5),
      one patient with mild neurological defect (GOS 4), and one patient with severe
      neurological defect (GOS 3) at discharge. Meanwhile, there were 26 patients with
      modified Rankin Scale (MRS) 0-1, 4 patient with MRS 2, and one patient with MRS 3
      at discharge. There were four patients lost during the follow-up. During the
      follow-up, 26 patients had normal neurological function (GOS 5), and one patient
      with severe neurological defect (GOS 3). Meanwhile, there were 25 patients with
      MRS 0-1, one patient with MRS 2, and one patient with MRS 3. All patients had no
      recurrence of intracranial aneurysms after operation. CONCLUSIONS: The current
      case series found that minimally invasive surgical approach and intraoperative
      monitoring, supplemented by effective management of cerebrovascular perfusion,
      circulation and coagulation, can promote the treatment of intracranial aneurysms
      and prevent the development of cerebral ischemia and aneurysm rupture in Chinese
      patients with ischemic cerebrovascular diseases. Future studies with large sample
      size will be needed to confirm the results from the current case series.

PMID- 30217171
TI  - Validation of a frailty index in older cancer patients with solid tumours.
AB  - BACKGROUND: Frailty is an indicator of physiological reserve in older people. In
      non-cancer settings, frailty indices are reliable predictors of adverse health
      outcomes. The aims of this study were to 1) derive and validate a frailty index
      (FI) from comprehensive geriatric assessment (CGA) data obtained in the solid
      tumour chemotherapy setting, and 2) to explore whether the FI-CGA could predict
      chemotherapy decisions and survival in older cancer patients with solid tumours.
      METHODS: Prospective cohort study of a consecutive series sample of 175 cancer
      patients aged 65 and older with solid tumours. A frailty index was calculated
      using an accumulated deficits model, coding items from the comprehensive
      geriatric assessment tool administered prior to chemotherapy decision-making. The
      domains of physical and cognitive functioning, nutrition, mood, basic and
      instrumental activities of daily living, and comorbidities were incorporated as
      deficits into the model. RESULTS: The FI-CGA had a right-skewed distribution,
      with median (interquartile range) of 0.27 (0.21-0.39). The 99% limit to deficit
      accumulation was below the theoretical maximum of 1.0, at 0.75. The FI-CGA was
      significantly related (p < 0.001) to vulnerability as assessed by the Vulnerable
      Elders Survey-13 and to medical oncologists' assessments of fitness or
      vulnerability to treatment. Baseline frailty as determined by the FI-CGA was also
      associated with treatment decisions (Treatment Terminated, Treatment Completed,
      No Planned Treatment) (p < 0.001), with the No Planned Treatment group
      significantly frailer than the other two groups. CONCLUSION: The FI-CGA is a
      potentially useful adjunct to cancer clinical decision-making that could predict
      chemotherapy outcomes in older patients with solid tumours.

PMID- 30217172
TI  - Effect of interferon beta-1a subcutaneously three times weekly on clinical and
      radiological measures and no evidence of disease activity status in patients with
      relapsing-remitting multiple sclerosis at year 1.
AB  - BACKGROUND: In the PRISMS study, interferon beta-1a subcutaneously (IFN beta-1a
      SC) reduced clinical and radiological disease burden at 2 years in patients with
      relapsing-remitting multiple sclerosis. The study aimed to characterize efficacy
      of IFN beta-1a SC 44 MUg and 22 MUg three times weekly (tiw) at Year 1. METHODS:
      Exploratory endpoints included annualized relapse rate (ARR), 3-month confirmed
      disability progression (1-point Expanded Disability Status Scale increase if
      baseline was < 6.0 [0.5-point if baseline was >=6.0]), active T2 lesions, and no
      evidence of disease activity (NEDA; defined as no relapses [subanalyzed by
      relapse severity], 3-month confirmed progression, or active T2 lesions). Effect
      of IFN beta-1a SC in prespecified patient subgroups was also assessed. RESULTS:
      Patients were randomized to IFN beta-1a 22 MUg (n = 189), 44 MUg (n = 184), or
      placebo (n = 187). At 1 year, IFN beta-1a SC tiw reduced ARR (p < 0.001), risk of
      disability progression (p <= 0.029), and mean number of active T2 lesions per
      patients per scan (p < 0.001) versus placebo. Clinical and radiological benefits
      were seen as early as Month 2 and 3. Outcomes in subgroups were consistent with
      those in the overall population. More patients treated with IFN beta-1a SC tiw
      achieved NEDA status, versus placebo, regardless of relapse severity (p <=
      0.006). CONCLUSION: Clinical, radiological, and NEDA outcomes at Year 1 were
      consistent with Year 2 results. Treatment efficacy was consistent in pre
      specified patient subgroups.

PMID- 30217173
TI  - Notch polymorphisms associated with sensitivity of noise induced hearing loss
      among Chinese textile factory workers.
AB  - BACKGROUND: Noise induced hearing loss (NIHL) is a polygenic disease involving
      both genetic and environmental factors, and is one of the most important
      occupational health hazards worldwide. To date, the influence of Notch1 variants
      on the risk to develop NIHL has not been illuminated. This study was conducted to
      explore the effects of Notch1 polymorphisms on individual susceptibility to NIHL.
      METHODS: A total of 2689 industrial workers from one textile factory in east
      China were recruited to participate in the current study. Venous blood was
      collected, basic clinical data was obtained by questionnaires and pure-tone
      audiometry (PTA) tests were conducted by specialist physicians. Next we performed
      genotyping of three selected SNPs (rs3124594, rs3124599 and rs3124603) in the
      Notch1 gene in 535 NIHL patients and 535 controls. Subsequently, the main effects
      of the genotypes and their interactions were evaluated. RESULTS: Our results
      revealed that individuals with a GG of rs3124594, TT of rs3124603 (OR = 4.70 and
      1.59 respectively) and the haplotype AAC (rs3124594-rs3124599-rs3124603) (OR =
      14.95) were associated with an increased risk of NIHL in our study cohort.
      Stratified analysis showed that an increased NIHL risk was found in individuals
      exposed to work related noise for <=16 years that also had the rs3124594 GG or
      rs3124603 CT/TT genotype with an OR of 4.20 and 1.73 respectively. Multifactor
      dimensionality reduction analysis indicated that rs3124594, rs3124599 and
      rs3124603 interacted with each other and were related to an increased risk to
      develop NIHL (OR = 3.60). CONCLUSIONS: The genetic polymorphisms rs3124594 and
      rs3124603 within the Notch1 gene are associated with an increased risk of NIHL in
      a Chinese population and could potentially be used as biomarkers for NIHL in
      noise exposed workers.

PMID- 30217174
TI  - Anticholinergic burden and comorbidities in patients attending treatment with
      trospium chloride for overactive bladder in a real-life setting: results of a
      prospective non-interventional study.
AB  - BACKGROUND: Elderly people are representative for the patients most likely to be
      treated with anticholinergics for overactive bladder (OAB). They often receive
      further drugs with anticholinergic properties for concomitant conditions. This
      increases the risk for side effects, including central nervous system disorders.
      Data on comorbidities and baseline anticholinergic burden of OAB patients seen in
      urological practice is scarce. Therefore, we included an epidemiological survey
      on these issues in our study which assessed the effectiveness and tolerability of
      trospium chloride (TC) in established dosages under routine conditions. METHODS:
      Outpatients (>= 65 years of age), for whom treatment with TC was indicated, were
      eligible to participate in this non-interventional, prospective study performed
      in 162 urological practices in Germany. Epidemiological questions were evaluated
      by the Anticholinergic Burden (ACB) scale and the Cumulative Illness Rating Scale
      for Geriatrics (CIRS-G) at baseline. Efficacy was assessed by changes in symptom
      related variables of OAB after treatment. Dosage regimen, duration of treatment,
      adverse events, withdrawals, and ease of subdivision of the prescribed SNAP-TAB
      tablet were documented. Patients and physicians rated efficacy and tolerability
      of treatment. Statistics were descriptive. RESULTS: Four hundred fourty-five out
      of 986 (47.54%) patients in the epidemiological population had a baseline ACB
      scale score > 0, 100 (24.72%) of whom a score >= 3. The median CIRS-G comorbidity
      index score for all patients was 5. 78.55% (608/774) of patients in the efficacy
      population received a daily dose of 45 mg TC. 60.03% (365/608) of them took this
      dose by dividing the SNAP-TAB tablet in three equal parts. Before-after
      comparisons of the core symptoms of OAB showed clear improvements. An influence
      of the dosage scheme (1 * 45 mg TC/d vs 3 * 15 mg TC/d) on clinical outcome could
      not be observed. Most urologists and patients rated TC treatment as effective and
      well tolerated. 44 (4.37%) out of 1007 patients in the safety collective ended
      their treatment prematurely, while 75 patients (7.45%) experienced adverse
      events. CONCLUSIONS: Anticholinergic burden and comorbidities in elderly OAB
      patients are frequent. The acceptance of the SNAP-TAB tablet, which facilitates
      flexible dosing with TC, was high, which is supportive in ensuring adherence in
      therapy. TRIAL REGISTRATION: This non-interventional study was registered on
      October 29, 2014 with the number DRKS00007109 at the German Register of Clinical
      Studies (DRKS).

PMID- 30217175
TI  - High cryptic species diversity is revealed by genome-wide polymorphisms in a wild
      relative of banana, Musa itinerans, and implications for its conservation in
      subtropical China.
AB  - BACKGROUND: Species delimitation is a challenging but essential task in
      conservation biology. Morphologically similar species are sometimes difficult to
      recognize even after examination by experienced taxonomists. With the advent of
      molecular approaches in species delimitation, this hidden diversity has received
      much recent attention. In addition to DNA barcoding approaches, analytical tools
      based on the multi-species coalescence model (MSC) have been developed for
      species delimitation. Musa itinerans is widely distributed in subtropical Asia,
      and at least six varieties have been documented. However, the number of
      evolutionarily distinct lineages remains unknown. RESULTS: Using genome
      resequencing data of five populations (making up four varieties), we examined
      genome-wide variation and found four varieties that were evolutionary significant
      units. A Bayesian Phylogenetics and Phylogeography (BP&P) analysis using 123
      single copy nuclear genes support three speciation events of M. itinerans
      varieties with robust posterior speciation probabilities; However, a Bayes factor
      delimitation of species with genomic data (BFD*) analysis using 1201 unlinked
      single nucleotide polymorphisms gave decisive support for a five-lineage model.
      When reconciling divergence time estimates with a speciation time scale, a
      modified three-lineage model was consistent with that of BP&P, in which the
      speciation time of two varieties (M. itinerans var. itinerans and M. itinerans
      var. lechangensis) were dated to 26.2 kya and 10.7 kya, respectively. In
      contrast, other two varieties (M. itinerans var. chinensis and M. itinerans var.
      guangdongensis) diverged only 3.8 kya in the Anthropocene; this may be a
      consequence of genetic drift rather than a speciation event. CONCLUSION: Our
      results showed that the M. itinerans species complex harbours high cryptic
      species diversity. We recommend that M. itinerans var. itinerans and M. itinerans
      var. lechangensis be elevated to subspecies status, and the extremely rare latter
      subspecies be given priority for conservation. We also recommend that the very
      recently diverged M. itinerans var. chinensis and M. itinerans var.
      guangdongensis should be merged under the subspecies M. itinerans var. chinensis.
      Finally, we speculate that species delimitation of recently diverged lineages may
      be more effective using genome-wide bi-allelic SNP markers with BFD* than by
      using unlinked loci and BP&P.

PMID- 30217176
TI  - EGFR mutation frequency in Middle East and African non-small cell lung cancer
      patients: a systematic review and meta-analysis.
AB  - BACKGROUND: Our goal was to investigate the prevalence of the epidermal growth
      factor receptor (EGFR) mutation in Middle East and African countries and to
      compare its prevalence with that shown in other populations. METHODS: We used
      PubMed and the Cochrane Library databases to conduct a literature search using
      the terms "[EGFR] AND [mutation] AND [Non Small Cell Lung Cancer] AND [Middle
      East OR Africa]." We assessed studies published in English and French from 2004
      until 2016. RESULTS: Ten relevant studies were included in this systematic
      review. Overall, 1215 patients with non-small cell lung cancer (NSCLC) were
      included in this analysis. The overall ratio of male to female patients was 2.15.
      Of total patients included, 41.1% had never smoked and 85.8% had been diagnosed
      with adenocarcinoma. In 8 of the 10 studies, polymerase chain reaction (PCR)
      analyses were conducted to identify EGFR mutations. In total, 257 patients had an
      EGFR mutation, corresponding to a prevalence of 21.2%. The most frequent
      abnormality detected in all of the studies was in exon 19. In addition, all
      studies concluded the presence of a correlation between EGFR mutation status and
      female sex, non-smoking status, and adenocarcinoma subtype. CONCLUSIONS: The EGFR
      mutation frequency in Middle East and African patients is higher than that shown
      in white populations but still lower than the frequency reported in Asian
      populations.

PMID- 30217177
TI  - A prospective case-control study comparing optical coherence tomography
      characteristics in neuromyelitis optica spectrum disorder- optic neuritis and
      idiopathic optic neuritis.
AB  - BACKGROUND: Neuromyelitis optica spectrum disorder-optic neuritis (NMOSD-ON) can
      now be distinguished from other types of ON as a specific disease by the
      Aquaporin-4 antibody (AQP4-Ab) test. NMOSD-ON can cause severe retinal nerve
      fiber layer (RNFL) damage. The optical coherence tomography (OCT) characteristics
      between NMOSD- ON and idiopathic optic neuritis (IDON) were seldom studied in
      Asians. METHODS: This prospective case-control study involved 152 eyes from 143
      optic neuritis (ON) patients. All the patients were divided into either the NMOSD
      ON group or the IDON group based on the AQP4-Ab test. The retinal nerve fiber
      layer thickness (RNFLT), retinal thickness (RT), and choroidal thickness (CT)
      were measured by spectral-domain OCT and compared to the 60 age- and gender
      matched healthy controls. The association between RNFLT and best corrected visual
      acuity (BCVA) was examined. RESULTS: The RNFLT was significantly thinner in all
      ON patients than in healthy controls, while NMOSD-ON eyes were significantly more
      affected than IDON eyes in all quadrants (p < 0.01). NMOSD-ON patients had
      stronger visual function impairment than IDON patients (p < 0.01). RNFLT was
      related to BCVA in both the NMOSD-ON and IDON groups. Microcystic macular edema
      (MME) was identified in 28 patients (19.58%) and in 29 of 152 eyes (19.08%),
      including 20 of 40 eyes (50%) previously affected by ON. MME was more common in
      patients with NMOSD-ON (32.2%) than in those with IDON (10.75%) (p = 0.001).
      CONCLUSIONS: The NMOSD-ON group had more pronounced RNFLT thinning and visual
      function impairment than the IDON group. MME prevalence was higher in NMOSD-ON
      and was associated with higher frequency of clinical relapses.

PMID- 30217178
TI  - Molecular characterization of the genome-wide BOR transporter gene family and
      genetic analysis of BnaC04.BOR1;1c in Brassica napus.
AB  - BACKGROUND: Boron (B) deficiency is an agricultural problem that causes
      significant losses of crop yield in many areas of the world. However, systematic
      analysis of BOR family genes for B transport in rapeseed is still lacking. We
      aimed to identify and characterize BOR transporters in Brassica napus and the
      potential role of these transporters in B homeostasis in response to B
      deficiency. RESULTS: Here, we identified 20 BOR transporters from the Brassica
      napus genome, which were classified into six distinct groups that represent clear
      orthologous relationships to their family members in Arabidopsis. qRT-PCR
      revealed distinct expression profiles for BnBORs in different tissues and in
      response to external B levels. The B-efficient cultivar QY10 accumulated more B
      in shoots than the B-inefficient cultivar W10, and overexpression of BnaBOR1;1c
      could alleviate shoot B-deficiency symptoms in W10 by distributing more B from
      roots to shoots. Additionally, BnBOR1;1c expression was up-regulated by B
      deficiency, and the induction of BnBOR1;1c was more intense in QY10. Moreover,
      two conserved InDels were found in the promoter regions of BnBOR1;1c within
      different B-efficient genotypes. CONCLUSIONS: Overall, the molecular
      characterization of the BnBOR genes of two B-efficient cultivars and their
      responses to B deficiency highlights the diversity of the family members in B.
      napus, and BnaC4.BOR1;1c has potential as a candidate gene for improving B
      nutrition.

PMID- 30217179
TI  - Evaluation of continuous constant current and continuous pulsed current in sweat
      induction for cystic fibrosis diagnosis.
AB  - BACKGROUND: The sweat test (ST) is the gold standard for the diagnosis of cystic
      fibrosis (CF). However, little is known about sweat induction using different
      types of currents and waves. In this context, our objective was to develop a
      device to induce sweat and compare the use of continuous constant current (CCC)
      and continuous pulsed current (CPC) in individuals with CF and healthy controls.
      METHODS: A prospective cross-sectional study with experimental intervention. The
      variables of gender, ethnicity, age, and body mass index (BMI) were considered.
      The method of Gibson and Cooke was used, and the following markers were
      evaluated: sweat weight, electrical impedance, sufficient sweat amount, and CF
      diagnosis. Triangular (TPC) or sinusoidal (SPC) pulsed current was applied to the
      right arm, and CCC was applied to the left arm. RESULTS: The study analyzed 260
      individuals, 141/213 (54.2%) were female participants, 135/260 (51.9%) were
      Caucasians. The distribution of individuals by concentration of chloride at the
      ST was: (CF) 26/260 (10%); (borderlines) 109/260 (41.9%); (healthy) 97/260
      (37.3%); (insufficient weight in sweat) 28/260 (10.8%). No association was
      observed between the sufficient sweat amount to perform the ST when we compared
      the currents. However, the SPC showed a higher amount of sweat weight. Using
      Bland and Altman plot considering the agreement between the sweat chloride values
      achieved from CPC [SPC and TPC] and CCC, there was no proportional bias and mean
      values are unrelated and only explain less than 8% of the variation. Moreover,
      TPC presented higher electrical impedance when compared with SPC and CCC. SPC
      presented lower electrical impedance and higher sweat weight than CCC. Male
      participants presented lower electrical impedance and higher sweat weight with
      CCC and TPC, and higher sweat weight with SPC. CONCLUSIONS: The evaluated
      currents are safe and able to induce and produce sweat in sufficient quantities
      for the ST. SPC presented lower electrical impedance when compared with other
      currents. The use of SPC is recommended to induce sweat in patients with sweat
      problems. Finally, ethnicity, gender, age and BMI did not influence sweat
      induction at the ST, and no side effect was observed in our study.

PMID- 30217180
TI  - Prevalence of intestinal parasitic infections and associated risk factors for
      hookworm infections among primary schoolchildren in rural areas of Nakhon Si
      Thammarat, southern Thailand.
AB  - BACKGROUND: Soil-transmitted helminth (STH) infections are among the most common
      type of infections worldwide and are widely distributed in tropical areas. In
      rural areas of southern Thailand where most land is used for agriculture,
      children are at risk of acquiring parasites, especially STHs. Assessing the
      current situation regarding parasitic infection in these areas is a prerequisite
      for developing appropriate control measures. This study is aimed at determining
      the prevalence of intestinal parasitic infections, the intensity of STH
      infections and the associated risk factors among primary schoolchildren in
      Nopphitam District, Nakhon Si Thammarat Province, Thailand. METHODS: A cross
      sectional study involving 299 schoolchildren between 7 and 12 years of age was
      conducted between January and March 2016. A questionnaire administered by direct
      interviews was used to collect sociodemographic information and data on
      associated risk factors. Stool samples were processed using direct wet smears,
      formalin-ethyl acetate sedimentation concentration, and the modified Kato-Katz
      technique. RESULTS: The overall prevalence of intestinal parasites among the 299
      children was 16% (48 of 299), with 32 children infected with hookworms (10.7%),
      10 with Blastocystis hominis (3.3%), seven with Giardia intestinalis (1.6%), one
      with Enterobius vermicularis (0.3%), and one with Trichuris trichiura (0.3%). The
      hookworm infection intensity, measured by the median eggs per gram (EPG) of
      stool, was 1200 EPG (Interquartile range (IQR): 360-3200). Most children had
      light-intensity hookworm infections, but two had heavy-intensity infections. When
      participants included in the sample were classified by age, children 10-12 years
      old demonstrated higher intestinal parasite prevalence than those aged 7-9 years
      (adjusted odds ratio (AOR) = 2.3, 95% CI: 1.1-4.9, P = 0.030). Inadequate
      handwashing before meals was statistically associated with hookworm infections
      (AOR = 2.3; 95% CI: 1.1-4.8, P = 0.037). CONCLUSIONS: This study highlights that
      hookworms are the most prevalent STH infection in the study area. Older age group
      (10-12 years) and inadequate handwashing before meals were statistically
      associated with hookworm infections. Accordingly, appropriate strategies and
      education on personal and environmental hygiene should be implemented. Moreover,
      the cost-effectiveness of mass drug administration in this area should be further
      investigated.

PMID- 30217181
TI  - Peritoneal dialysis catheter outcomes in infants initiating peritoneal dialysis
      for end-stage renal disease.
AB  - BACKGROUND: End-stage renal disease (ESRD) although rare among infants presents
      many management challenges. We sought to evaluate factors associated with PD
      catheter failure among infants initiated on chronic PD. METHODS: A retrospective
      chart review of all children under two years of age who had PD catheters placed
      for initiation of chronic PD from 2002 to 2015. Data was extracted for catheter
      related events occurring within 12 months of catheter placement. Cox and Poisson
      regression models were used to delineate factors associated catheter
      complications. RESULTS: Twenty-five infants with median age 18 days had PD
      catheters placed for chronic dialysis. Common complications included leakage
      around the exit site (31%), blockage (26%), migration or malposition (23%),
      catheter-related infections (18%), and other complications (2%). Predictors of
      initial PD catheter failure were age less than one month at catheter placement
      (hazard ratio (HR) 7.77, 95% CI, 1.70-35.39, p = 0.008), use of catheter within
      three days of placement (HR 5.67, 95% CI, 1.39-23.10, p = 0.015) and presence of
      a hernia (HR 8.64, 95% CI, 1.19-62.36, p = 0.033). In an adjusted Poisson
      regression model, PD catheter use within three days of placement was the only
      predictor of any catheter complication over the12 months of follow up.
      CONCLUSIONS: Use of PD catheters within three days of placement was associated
      with catheter failure. We recommend that when possible, catheters should be
      allowed to heal for at least three days prior to use to reduce risk of
      complications and improve catheter survival.

PMID- 30217182
TI  - Nordic walking training and nutritional supplementation in pre-frail older
      Indians: an open-labelled experimental pre-test and post-test pilot study to
      develop intervention model.
AB  - BACKGROUND: Identifying and treating people in a pre-frail state may be an
      effective way to prevent or delay frailty and preserve their functional capacity.
      This study aimed to assess the efficacy of, and compliance with, a 12 week
      individualized nutritional supplementation (INS) and Nordic walking (NW) program
      in pre-frail older Indians. The primary measure is physical performance, as
      indicated by Fried's Frailty scale. Other measures include: cognition, as
      indicated by the Hindi Mental Status Examination; mood, by the Geriatric
      Depression Scale; and nutritional status, by the Mini Nutritional Assessment.
      METHODS: This is an open-labeled experimental pre-test and post-test study, which
      took place from October 2012 to December 2014. The study was approved by
      Institute Ethics committee (IEC/NP-350/2012/RP-26/2012) at the All India
      Institute of Medical Sciences (AIIMS), New Delhi. Participants were sixty-six pre
      frail elderly, who were randomly allocated into three subgroups, namely: A (NW
      only), B (INS only), and C (NW and INS). One-way ANOVA was used to statistically
      assess differences in baseline characteristics for quantitative variables, with
      the Chi-Square/Fischer exact test utilized for qualitative variables. Paired t
      tests were used to assess pre and post intervention difference within the group
      for quantitative variables, with McNemar's Chi-Square test used for qualitative
      variables. Kruskal Wallis test was used to assess significant intervention
      effects among the groups. A p-value < 0.05 was considered as statistically
      significant. RESULTS: There was significant effect of intervention in gait speed
      in group A (p = 0.001) and C (p = 0.002), but not in group B (p = 0.926). While
      there was no significant change in grip strength in Group A (p = 0.488) and B (p
      = 0.852), a statistically significant increase was observed in group C (p =
      0.013). Mood significantly improved in group B (p = 0.025) and C (p = 0.021). No
      significant difference was noted in cognitive status across groups. Following the
      interventions, a total of 18.18% of pre-frail participants were classified as non
      frail. CONCLUSIONS: Combining NW and INS provides a simple, pragmatic
      intervention with efficacy in the management of functionally vulnerable older
      adults, and allows their maintained independence. Future studies should replicate
      this readily applicable intervention in a larger cohort with a longer follow-up
      period. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2016/05/006937
      [Registered on: 16/05/2016]; Trial was Registered Retrospectively.

PMID- 30217183
TI  - Long-term efficacy and safety of anti-VEGF therapy in retinitis pigmentosa: a
      case report.
AB  - BACKGROUND: Retinitis pigmentosa (RP), a neurodegenerative disease, is
      occasionally accompanied by choroidal neovascularization (CNV) and cystoid
      macular oedema. It is presently treated with repeated intravitreal injections of
      anti-vascular endothelial growth factor (VEGF) agents. However, there are
      concerns regarding long-term inhibition of VEGF by the use of these agents,
      especially in cases involving neurodegenerative diseases, since VEGFs have a
      neuroprotective effect. Currently, there are no reports on the long-term safety
      of anti-VEGF therapy in patients with RP. CASE PRESENTATION: In this report, we
      describe the case of a 56-year-old female patient with CNV associated with RP who
      was treated with anti-VEGF therapy for 8 years. She had autosomal dominant RP
      with a heterozygous PRPH2 mutation (c.410G > A) and complained of metamorphopsia
      in her left eye. Examinations revealed CNV with serous retinal detachment. She
      was treated with as-needed injections for 2 years; however, she experienced a
      recurrence. Therefore, we switched to a bimonthly regimen that was continued for
      6 years. In total, the patient received 34 injections of various types of anti
      VEGFs over 8 years. No recurrences were noted during that time, and we have not
      detected any negative effects concerning the progression of visual field loss in
      comparison with the fellow eye. CONCLUSIONS: No negative effects related to the
      progression of visual field loss were observed during continuous treatment with
      anti-VEGF agents for 8 years in our patient.

PMID- 30217184
TI  - Association between GDF5 rs143383 genetic polymorphism and musculoskeletal
      degenerative diseases susceptibility: a meta-analysis.
AB  - BACKGROUND: Several studies have assessed the association between GDF5 rs143383
      polymorphism and the susceptibility of musculoskeletal degenerative diseases,
      such as intervertebral disc degeneration (IDD) and osteoarthritis (OA), but the
      results are inconsistent. The aim of our study was to evaluate the association
      between them comprehensively. METHODS: A systematical search was conducted on
      PubMed, Scopus, Web of Science (WOS), Embase, and the Cochrane Library databases
      updated to April 20, 2018. Eligible studies about polymorphisms in GDF5 gene and
      risk of IDD or OA were included. Pooled odds ratios (ORs) and 95% confidence
      intervals (95% CIs) were utilized. RESULTS: Fifteen studies with a total of 5915
      cases and 12,252 controls were finally included in our study. Meta-analysis of
      GDF5 rs143383 polymorphism was statistically associated with increased risk of
      musculoskeletal degenerative diseases under each genetic model (allele model: OR
      = 1.32, 95% CI 1.19-1.48, P = 0.000; homozygote model: OR = 1.80, 95%CI 1.49
      2.16, P = 0.000; heterozygote model: OR = 1.37, 95%CI 1.21-1.55, P = 0.000;
      dominant model: OR = 1.56, 95%CI 1.39-1.75, P = 0.000; recessive model: OR =
      1.39, 95%CI 1.20-1.60, P = 0.000). Stratified analyses based on disease type
      showed a significant association between the GDF5 rs143383 polymorphism and
      increased risk of IDD and OA under all genetic models studied. When stratified
      with ethnicity, pooled outcomes revealed that this polymorphism was significantly
      related with increased risk of musculoskeletal degenerative diseases in both
      Asian and Caucasian populations under all genetic models studied. CONCLUSIONS:
      The present study suggested that GDF5 rs143383 polymorphism was significantly
      associated with susceptibility to musculoskeletal degenerative diseases.

PMID- 30217185
TI  - Nutritional status, dental caries and tooth eruption in children: a longitudinal
      study in Cambodia, Indonesia and Lao PDR.
AB  - BACKGROUND: Untreated dental caries is reported to affect children's nutritional
      status and growth, yet evidence on this relationship is conflicting. The aim of
      this study was to assess the association between dental caries in both the
      primary and permanent dentition and nutritional status (including underweight,
      normal weight, overweight and stunting) in children from Cambodia, Indonesia and
      Lao PDR over a period of 2 years. A second objective was to assess whether
      nutritional status affects the eruption of permanent teeth. METHODS: Data were
      used from the Fit for School - Health Outcome Study: a cohort study with a follow
      up period of 2 years, consisting of children from 82 elementary schools in
      Cambodia, Indonesia and Lao PDR. From each school, a random sample of six to
      seven-year-old children was selected. Dental caries and odontogenic infections
      were assessed using the World Health Organization (WHO) criteria and the pufa
      index. Weight and height measurements were converted to BMI-for-age and height
      for-age z-scores and categorized into weight status and stunting following WHO
      standardised procedures. Cross-sectional and longitudinal associations were
      analysed using the Kruskal Wallis test, Mann Whitney U-test and multivariate
      logistic and linear regression. RESULTS: Data of 1499 children (mean age at
      baseline = 6.7 years) were analyzed. Levels of dental caries and odontogenic
      infections in the primary dentition were significantly highest in underweight
      children, as well as in stunted children, and lowest in overweight children.
      Dental caries in six to seven-year old children was also significantly associated
      with increased odds of being underweight and stunted 2 years later. These
      associations were not consistently found for dental caries and odontogenic
      infections in the permanent dentition. Underweight and stunting was significantly
      associated with a lower number of erupted permanent teeth in children at the age
      of six to seven-years-old and 2 years later. CONCLUSIONS: Underweight and stunted
      growth are associated with untreated dental caries and a delayed eruption of
      permanent teeth in children from Cambodia, Indonesia and Lao PDR. Findings
      suggest that oral health may play an important role in children's growth and
      general development. TRIAL REGISTRATION: The study was restrospectively
      registered with the German Clinical Trials Register, University of Freiburg
      (trial registration number: DRKS00004485 ; date of registration: 26th of
      February, 2013).

PMID- 30217186
TI  - Feasibility study of the SWITCH implementation process for enhancing school
      wellness.
AB  - BACKGROUND: There is a need to identify strategies that enhance the
      implementation of evidence-based school wellness intervention programs in real
      world settings. The present study evaluates the feasibility of empowering school
      wellness leaders to deliver an evidence-based, childhood obesity-prevention
      program called Switch TM. We specifically evaluated the feasibility of a new
      implementation framework, based on the robust Healthy Youth Places framework, to
      increase capacity of school leaders to lead school wellness programming. METHODS:
      The SWITCH (School Wellness Integration Targeting Child Health) implementation
      process was evaluated in a convenience sample of eight Iowa elementary schools.
      Teams of three leaders from each school attended an in-person school wellness
      conference followed by five online webinar sessions delivered by two SWITCH team
      members. The capacity-building and quality improvement process was designed to
      empower schools to lead wellness change using methods and concepts from the
      original 16-week Switch TM program. School wellness leaders completed checklists
      on two occasions to assess overall school-level implementation as well as setting
      level changes in physical education, classrooms, and the lunchroom. Student
      acceptability of SWITCH was evaluated by the degree of behavior tracking using an
      online SWITCH Tracker system that promoted self-monitoring. School acceptability
      and practicality were assessed through an exit survey completed by school
      leaders. RESULTS: All school staff reported satisfaction with the SWITCH
      implementation process. Reports of school- and setting-level implementation were
      relatively high (2.0 to 2.8 on a 3-point scale) but student engagement, based on
      use of the online tracking system, varied greatly over time and across schools.
      Three high implementation schools had average tracking rates exceeding 70%
      (range: 72-90%) while three low implementation schools had rates lower than 30%
      (range = 0-23%). CONCLUSIONS: This feasibility study supports the utility of the
      new implementation framework for promoting school and student engagement with
      SWITCH. Further testing regarding effectiveness and scale-up of this evidence
      based school wellness intervention program is warranted.

PMID- 30217187
TI  - Public health impact of a novel smoking cessation outreach program in Ontario,
      Canada.
AB  - BACKGROUND: Provision of evidence-based smoking cessation treatment may
      contribute to health disparities if barriers to treatment are greater for more
      disadvantaged groups. We describe and evaluate the public health impact of a
      novel outreach program to improve access to smoking cessation treatment in
      Ontario, Canada. METHODS: We partnered with Public Health Units (PHUs) located
      across the province to deliver single-session workshops providing standardized
      evidence-based content and 10 weeks (2007-2008) or 5 weeks (2008-2016) of
      nicotine replacement therapy (NRT). Participants completed a baseline assessment
      and were followed up by phone or e-mail at 6 months. We used the RE-AIM (Reach,
      Effectiveness, Adoption, Implementation and Maintenance) framework to evaluate
      the public health impact of the program from 2007 to 2016. Given the iterative
      design and changes in implementation over time, data is presented annually or bi
      annually. RESULTS: There were 26,122 enrollments from 2007 to 2016. Between 31
      and 442 workshops were held annually. The annual reach was estimated to be 0.1
      0.3% of eligible smokers in Ontario. Participants were older, smoked more
      heavily, had a lower household income, were more likely to be female and be
      diagnosed with a mood or anxiety disorder, and less likely to have a
      postsecondary degree compared to average Ontario smokers eligible for
      participation. The intervention was effective; at 6-month follow-up 22-33% of
      respondents reported abstinence from smoking. Adoption by PHUs was 81% by the
      second year of operation and remained high (72-97%) thereafter, with the
      exception of 2009-2010 (33-56%) when the program was temporarily unavailable to
      PHUs due to lack of funding. Implementation at the organizational level was not
      tracked; however, at the individual level, approximately half of participants
      used most or all of the NRT received. On average, maintenance of the program was
      high, with PHUs conducting workshops for 7 of the 10 years (2007-2016) and 4 of
      the 5 most recent years (2012-2016). CONCLUSIONS: The smoking cessation program
      had a high rate of adoption and maintenance, reached smokers over a large
      geographic area, including individuals more likely to experience disparities, and
      helped them make successful quit attempts. This novel model can be adopted in
      other jurisdictions with limited resources.

PMID- 30217188
TI  - Two novel L2HGDH mutations identified in a rare Chinese family with L-2
      hydroxyglutaric aciduria.
AB  - BACKGROUND: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria
      neurometabolic disease that is inherited as an autosomal recessive mode and have
      a variety of symptoms, such as psychomotor developmental retardation, epilepsy,
      cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2
      HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA
      is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons.
      CASE PRESENTATION: We presented a rare patient primary diagnosis of L-2-HGA based
      on the clinical symptoms, magnetic resonance imaging (MRI), and gas
      chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the
      L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed
      two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G,
      p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift
      mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The
      mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)
      binding domain and predicted to be pathogenic. CONCLUSION: We predicted the
      homozygous missense mutation (c.407 A > G, p.K136R) was considered as the
      pathogenic mutation of the patient. The study highlights the power of pedigree
      analysis in order to interpret novel mutations.

PMID- 30217189
TI  - Potential role for nectin-4 in the pathogenesis of pre-eclampsia: a molecular
      genetic study.
AB  - BACKGROUND: Nectins are cell adhesion molecules that play a pivotal role in
      adherens junctions and tight junctions. Our previous study using whole-genome
      oligonucleotide microarrays revealed that nectin-4 was upregulated in pre
      eclamptic placentas. We investigated the role of nectin-4 in the etiology of pre
      eclampsia. METHODS: We investigated the expression of nectin-4 using real-time RT
      PCR, western blot and immunostaining. Additionally, we performed matrigel
      invasion assay and cytotoxicity assay using cells overexpressing the nectin-4.
      RESULTS: NECTIN4 transcripts were elevated in pre-eclamptic placentas relative to
      uncomplicated pregnancies. Nectin-4 protein levels in pre-eclamptic placentas
      were higher on a semi-quantitative western blot. Nectin-4 was localized at the
      apical cell membrane in syncytiotrophoblast cells and not at the adherens
      junctions. Nectin-4 was also detected in cytotrophoblasts and a subset of cells
      in the decidua. Nectin-4 overexpressing trophoblast cells migrated normally in
      the matrix. However, Natural killer (NK) cells showed a strong cytotoxic effect
      against nectin-4 overexpressing trophoblast cells. No causative genetic variation
      was evident in the NECTIN4 gene from a pre-eclamptic placenta. CONCLUSIONS: There
      are as yet unknown factors that induce nectin-4 overexpression in trophoblast
      cells that may contribute to abnormal placentation via an aberrant immune
      response and the onset of a pre-eclamptic pregnancy.

PMID- 30217190
TI  - Quality of life in persons with dementia using regional dementia care network
      services in Germany: a one-year follow-up study.
AB  - BACKGROUND: The majority of individuals with dementia live in the community;
      thus, regional dementia care networks are becoming increasingly more important
      for the provision of care. To date, four different types of dementia care
      networks have been identified in Germany (stakeholder, organisation, hybrid,
      mission); however, the effect on the quality of life of persons with dementia
      using such network services has not yet been examined. Moreover, the possible
      differences in the effect on the quality of life among the four types of dementia
      care networks have not been investigated. Therefore, the aim of the present study
      was to describe the changes over time in the quality of life of persons with
      dementia, assessing the association with the different types of dementia care
      networks. METHODS: Within the DemNet-D study, face-to-face interviews with
      persons with dementia and their primary caregivers were conducted to collect data
      of typical outcome parameters, such as quality of life (Quality of Life
      Alzheimers Disease: QoL-AD), sociodemographic data, social index (Scheuch
      Winkler), depression (Geriatric Depression Scale: GDS), challenging behaviour
      (Cohen-Mansfield Agitation Inventory: CMAI), capacities of daily living
      (Instrumental Activity of Daily Living: IADL), impairment due to dementia (FAST),
      and caregiver burden. In addition to these parameters, the differences in quality
      of life scores among the four types of dementia care networks were analysed using
      multi-level analysis. RESULTS: In total, 407 persons with dementia (79.1 years;
      60.1% female) and their caregivers were included in the analysis. Over 75% of the
      persons with dementia showed moderate to (very) severe impairments of dementia
      and at least one challenging behaviour. At baseline, 60.6% had a low social
      index. Quality of life was stable over one-year on a level slightly above average
      (baseline 29.1; follow-up 28.7). Multi-level analyses (p <  0.001; R2 = 0.183)
      show that persons with dementia with higher QoL-AD scores at baseline were
      associated with a decline at follow-up. No significant differences among the
      types of dementia care networks were found. CONCLUSION: Users of dementia care
      network services showed a stable QoL-AD score over time at a level slightly above
      average, indicating no decrease or worsening over time as expected. Therefore,
      dementia care network services can be considered as a beneficial model of care in
      terms of the quality of life of persons with dementia, regardless of their
      special organisational type.

PMID- 30217191
TI  - NLRP3 inflammasome-dependent pyroptosis is proposed to be involved in the
      mechanism of age-dependent isoflurane-induced cognitive impairment.
AB  - Wang Z et al. recently published a paper, titled "Critical role of NLRP3-caspase
      1 pathway in age-dependent isoflurane-induced microglial inflammatory response
      and cognitive impairment". The finding in this paper is consistent with our
      previous study on NLRP3-caspase-1 pathway. Here, we propose that NLRP3
      inflammasome-dependent pyroptosis may be involved in the mechanism of age
      dependent isoflurane-induced cognitive impairment and discuss that inhibiting
      NLRP3 inflammasome activation with a novel inhibitor MCC950 may ameliorate age
      dependent isoflurane-induced neuro-inflammation.

PMID- 30217192
TI  - AR-PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene
      transcription by promoting MAD1 degradation in ER-negative breast cancer.
AB  - BACKGROUND: Androgen receptor (AR) is expressed in 60%~ 70% oestrogen receptor
      (ER)-negative breast cancer (BC) cases and promotes the growth of this cancer
      subtype. Expression of prostate-derived Ets factor (PDEF), a transcription
      factor, is highly restricted to epithelial cells in hormone-regulated tissues.
      MYC and its negative regulator MAD1 play an important role in BC progression.
      Previously, we found that PDEF expression is strongly correlated with AR
      expression. However, the relationship between AR and PDEF and the function of
      PDEF in ER-negative BC proliferation are unclear. METHODS: AR and PDEF expression
      in ER-negative BC tissues and cell lines was determined by performing
      immunohistochemistry or western blotting. Protein expression levels and location
      were analysed by performing western blotting, RT-qPCR and immunofluorescence
      staining. Co-immunoprecipitation and chromatin immunoprecipitation assays were
      performed to validate the regulation of AR-PDEF-MAD1-MYC axis. Moreover, the
      effect of AR and PDEF on BC progression was investigated both in vitro and in
      vivo. RESULTS: We found that PDEF was overexpressed in ER-negative BC tissues and
      cell lines and appeared to function as an oncogene. PDEF expression levels were
      strongly correlated with AR expression in ER-negative BC, and PDEF transcription
      was positively regulated by AR. PDEF upregulated MYC-mediated gene transcription
      by promoting MAD1 degradation in ER-negative BC. Finally, we found that compared
      with the inhibition of AR expression alone, simultaneous inhibition of AR and
      PDEF expression further suppressed tumour proliferation both in vitro and in
      vivo. CONCLUSIONS: Our data highlight the role of the AR-PDEF-MAD1-MYC axis in BC
      progression and suggest that PDEF can be used as a new clinical therapeutic
      target for treating ER-negative BC.

PMID- 30217193
TI  - Physical activity, cardiovascular health, quality of life and blood pressure
      control in hypertensive subjects: randomized clinical trial.
AB  - BACKGROUND: Physical activity (PA) promotes cardiovascular health and health
      related quality of life (HRQoL), although the effect of that on blood pressure
      (BP) control has rarely been studied in hypertensive subjects. Our aim was to
      evaluate the effectiveness of a PA intervention programme on cardiovascular
      disease (CVD) risk, HRQoL and BP control in hypertensive subjects. METHODS: A
      randomized clinical trial, with a PA intervention programme of 9 months duration,
      comprising a walking group of 120 min/week, supervised, and with socio-cultural
      activities. Participants were 207 hypertensive subjects (68.2 years, 76.8%
      women). PA (IPAQ-s), diet, CVD risk, BP, BMI, smoking, and HRQoL (SF-36) were
      assessed at baseline and at the end of the intervention. Changes in CVD risk and
      in HRQoL during the intervention was calculated (end-baseline score).
      Multivariate models were applied. RESULTS: In multivariate models, the PA
      intervention programme, with no modification of the diet, decreased CVD risk (-
      1.19 points) and the systolic BP (- 8.68 mmHg), and increased some areas of HRQoL
      (4.45 to 14.62 points). An increase in the percentage of subjects with controlled
      BP was observed by the PA programme itself (OR 5.395 to 5.785 according to
      multivariate models), and by the changes during the intervention in the decrease
      in CVD risk (OR 0.609) and in the increase in the HRQoL in physical component
      summary (OR 1.041), role physical (OR 1.010), and bodily pain (OR 1.014),
      independently of controlled BP at baseline. CONCLUSIONS: This PA intervention
      programme improved cardiovascular health and HRQoL, and favoured BP control in
      primary care users with hypertension. TRIAL REGISTRATION: Clinicaltrials.gov ID
      NCT02767739 ; Trial registered on May 5th, 2016. Retrospectively registered.

PMID- 30217194
TI  - Automated cardiovascular magnetic resonance image analysis with fully
      convolutional networks.
AB  - BACKGROUND: Cardiovascular resonance (CMR) imaging is a standard imaging modality
      for assessing cardiovascular diseases (CVDs), the leading cause of death
      globally. CMR enables accurate quantification of the cardiac chamber volume,
      ejection fraction and myocardial mass, providing information for diagnosis and
      monitoring of CVDs. However, for years, clinicians have been relying on manual
      approaches for CMR image analysis, which is time consuming and prone to
      subjective errors. It is a major clinical challenge to automatically derive
      quantitative and clinically relevant information from CMR images. METHODS: Deep
      neural networks have shown a great potential in image pattern recognition and
      segmentation for a variety of tasks. Here we demonstrate an automated analysis
      method for CMR images, which is based on a fully convolutional network (FCN). The
      network is trained and evaluated on a large-scale dataset from the UK Biobank,
      consisting of 4,875 subjects with 93,500 pixelwise annotated images. The
      performance of the method has been evaluated using a number of technical metrics,
      including the Dice metric, mean contour distance and Hausdorff distance, as well
      as clinically relevant measures, including left ventricle (LV) end-diastolic
      volume (LVEDV) and end-systolic volume (LVESV), LV mass (LVM); right ventricle
      (RV) end-diastolic volume (RVEDV) and end-systolic volume (RVESV). RESULTS: By
      combining FCN with a large-scale annotated dataset, the proposed automated method
      achieves a high performance in segmenting the LV and RV on short-axis CMR images
      and the left atrium (LA) and right atrium (RA) on long-axis CMR images. On a
      short-axis image test set of 600 subjects, it achieves an average Dice metric of
      0.94 for the LV cavity, 0.88 for the LV myocardium and 0.90 for the RV cavity.
      The mean absolute difference between automated measurement and manual measurement
      is 6.1 mL for LVEDV, 5.3 mL for LVESV, 6.9 gram for LVM, 8.5 mL for RVEDV and 7.2
      mL for RVESV. On long-axis image test sets, the average Dice metric is 0.93 for
      the LA cavity (2-chamber view), 0.95 for the LA cavity (4-chamber view) and 0.96
      for the RA cavity (4-chamber view). The performance is comparable to human inter
      observer variability. CONCLUSIONS: We show that an automated method achieves a
      performance on par with human experts in analysing CMR images and deriving
      clinically relevant measures.

PMID- 30217195
TI  - Mutational Mtc6p attenuates autophagy and improves secretory expression of
      heterologous proteins in Kluyveromyces marxianus.
AB  - BACKGROUND: The yeast Kluyveromyces marxianus is an emerging cell factory for
      heterologous protein biosynthesis and its use holds tremendous advantages for
      multiple applications. However, which genes influence the productivity of desired
      proteins in K. marxianus has so far been investigated by very few studies.
      RESULTS: In this study, we constructed a K. marxianus recombinant (FIM1/Est1E),
      which expressed the heterologous ruminal feruloyl esterase Est1E as reporter. UV
      60Co-gamma irradiation mutagenesis was performed on this recombinant, and one
      mutant (be termed as T1) was screened and reported, in which the productivity of
      heterologous Est1E was increased by at least tenfold compared to the parental
      FIM1/Est1E recombinant. Transcriptional perturbance was profiled and presented
      that the intracellular vesicle trafficking was enhanced while autophagy be
      weakened in the T1 mutant. Moreover, whole-genome sequencing combined with
      CRISPR/Cas9 mediated gene-editing identified a novel functional protein Mtc6p,
      which was prematurely terminated at Tyr251 by deletion of a single cytosine at
      755 loci of its ORF in the T1 mutant. We found that deleting C755 of MTC6 in FIM1
      led to 4.86-fold increase in the production of Est1E compared to FIM1, while the
      autophagy level decreased by 47%; on the contrary, when reinstating C755 of MTC6
      in the T1 mutant, the production of Est1E decreased by 66% compared to T1, while
      the autophagy level increased by 124%. Additionally, in the recombinant with
      attenuated autophagy (i.e., FIM1 mtc6C755Delta and T1) or interdicted autophagy
      (i.e., FIM1 atg1Delta and T1 atg1Delta), the productivity of three other
      heterologous proteins was also increased, specifically the heterologous mannase
      Man330, the beta-1,4-endoxylanase XynCDBFV or the conventional EGFP. CONCLUSIONS:
      Our results demonstrated that Mtc6p was involved in regulating autophagy;
      attenuating or interdicting autophagy would dramatically improve the yields of
      desired proteins in K. marxianus, and this modulation could be achieved by
      focusing on the premature mutation of Mtc6p target.

PMID- 30217196
TI  - Severely malnourished children with a low weight-for-height have similar
      mortality to those with a low mid-upper-arm-circumference: II. Systematic
      literature review and meta-analysis.
AB  - BACKGROUND: The WHO recommended criteria for diagnosis of sever acute
      malnutrition (SAM) are weight-for-height/length Z-score (WHZ) of <- 3Z of the
      WHO2006 standards, a mid-upper-arm circumference (MUAC) of < 115 mm, nutritional
      oedema or any combination of these parameters. A move to eliminate WHZ as a
      diagnostic criterion has been made on the assertion that children with a low WHZ
      are healthy, that MUAC is a "superior" prognostic indicator of mortality and that
      adding WHZ to the assessment does not improve the prediction of death. Our
      objective was to examine the literature comparing the risk of death of SAM
      children admitted by WHZ or MUAC criteria. METHODS: We conducted a systematic
      search for reports which examined the relationship of WHZ and MUAC to mortality
      for children less than 60 months. The WHZ, MUAC, outcome and programmatic
      variables were abstracted from the reports and examined. Individual study's case
      fatality rates were compared by chi-squared analysis and random effects meta
      analyses for combined data. RESULTS: Twenty-one datasets were reviewed. All the
      patient studies had an ascertainment bias. Most were inadequate because they had
      insufficient deaths, used obsolete standards, combined oedematous and non
      oedematous subjects, did not report the proportion of children with both deficits
      or the deaths occurred remotely after anthropometry. The meta-analyses showed
      that the mortality risks for children who have SAM by MUAC < 115 mm only and
      those with SAM by WHZ < -3Z only are not different. CONCLUSIONS: As the
      diagnostic criteria identify different children, this analysis does not support
      the abandonment of WHZ as an important independent diagnostic criterion for the
      diagnosis of SAM. Failure to identify such children will result in their being
      denied treatment and unnecessary deaths from SAM.

PMID- 30217197
TI  - Metabolic engineering of Corynebacterium glutamicum for anthocyanin production.
AB  - BACKGROUND: Anthocyanins such as cyanidin 3-O-glucoside (C3G) have wide
      applications in industry as food colorants. Their current production heavily
      relies on extraction from plant tissues. Development of a sustainable method to
      produce anthocyanins is of considerable interest for industrial use. Previously,
      E. coli-based microbial production of anthocyanins has been investigated
      extensively. However, safety concerns on E. coli call for the adoption of a safe
      production host. In the present study, a GRAS bacterium, Corynebacterium
      glutamicum, was introduced as the host strain to synthesize C3G. We adopted
      stepwise metabolic engineering strategies to improve the production titer of C3G.
      RESULTS: Anthocyanidin synthase (ANS) from Petunia hybrida and 3-O
      glucosyltransferase (3GT) from Arabidopsis thaliana were coexpressed in C.
      glutamicum ATCC 13032 to drive the conversion from catechin to C3G. Optimized
      expression of ANS and 3GT improved the C3G titer by 1- to 15-fold. Further
      process optimization and improvement of UDP-glucose availability led to ~ 40 mg/L
      C3G production, representing a > 100-fold titer increase compared to production
      in the un-engineered, un-optimized starting strain. CONCLUSIONS: For the first
      time, we successfully achieved the production of the specialty anthocyanin C3G
      from the comparatively inexpensive flavonoid precursor catechin in C. glutamicum.
      This study opens up more possibility of C. glutamicum as a host microbe for the
      biosynthesis of useful and value-added natural compounds.

PMID- 30217198
TI  - Lipid nanoparticles loading triptolide for transdermal delivery: mechanisms of
      penetration enhancement and transport properties.
AB  - BACKGROUND: In recent years, nanoparticles (NPs) including nanostructured lipid
      carries (NLC) and solid lipid nanoparticles (SLN) captured an increasing amount
      of attention in the field of transdermal drug delivery system. However, the
      mechanisms of penetration enhancement and transdermal transport properties of NPs
      are not fully understood. Therefore, this work applied different platforms to
      evaluate the interactions between skin and NPs loading triptolide (TPL, TPL-NLC
      and TPL-SLN). Besides, NPs labeled with fluorescence probe were tracked after
      administration to investigate the dynamic penetration process in skin and skin
      cells. In addition, ELISA assay was applied to verify the in vitro anti
      inflammatory effect of TPL-NPs. RESULTS: Compared with the control group, TPL-NPs
      could disorder skin structure, increase keratin enthalpy and reduce the SC
      infrared absorption peak area. Besides, the work found that NPs labeled with
      fluorescence probe accumulated in hair follicles and distributed throughout the
      skin after 1 h of administration and were taken into HaCaT cells cytoplasm by
      transcytosis. Additionally, TPL-NLC could effectively inhibit the expression of
      IL-4, IL-6, IL-8, IFN-gamma, and MCP-1 in HaCaT cells, while TPL-SLN and TPL
      solution can only inhibit the expression of IL-6. CONCLUSIONS: TPL-NLC and TPL
      SLN could penetrate into skin in a time-dependent manner and the penetration is
      done by changing the structure, thermodynamic properties and components of the
      SC. Furthermore, the significant anti-inflammatory effect of TPL-NPs indicated
      that nanoparticles containing NLC and SLN could serve as safe prospective agents
      for transdermal drug delivery system.

PMID- 30217199
TI  - Development and validation of a dietary screener for carbohydrate intake in
      endurance athletes.
AB  - BACKGROUND: Studies have shown that the majority of endurance athletes do not
      achieve the minimal recommended carbohydrate (CHO) intake of 6 g/kg of body
      weight (BW), with potentially negative impacts on recovery and performance. The
      purpose of this study was to develop and validate a rapid and easy to use dietary
      screener to identify athletes who do and do not achieve a CHO intake > 6 g/kg BW
      in the context of endurance sports. METHODS: The dietary screener was developed
      using multiple logistic regression modeling of data from a sample of 1571 non
      athlete adults (826 women and 745 men, mean age 44.75 +/- 14.2 years) among whom
      dietary intake was assessed using a validated web-based food frequency
      questionnaire (web-FFQ). Three models were developed based on whole food intake
      using the 5, 10 and 15 most significant variables predicting CHO intake. The
      three models were then validated in a target population of non-elite endurance
      athletes having taken part in multisport events (n = 175, 64 women and 111 men,
      mean age 37.1 +/- 11.3 years) and compared using sensitivity, specificity,
      positive and negative predictive values (PPV and NPV, respectively) and c
      statistics. RESULTS: The 15-variables model provided significantly better
      accuracy in predicting CHO intake adequacy in non-elite endurance athletes (c
      statistic = 0.94) compared with the 10- and 5-variables model (c-statistic = 0.90
      and 0.71 respectively). The 15-variables model predicts CHO intake adequacy in
      the target population of endurance athlete with a sensitivity of 89.5%, a
      specificity of 87.3% and PPV and NPV of 77.3 and 94.5%, respectively. CONCLUSION:
      We have successfully developed a short and valid dietary screener that identifies
      endurance athletes at risk of not achieving a CHO intake > 6 g/kg BW. Use of this
      rapid screener may help alleviate the highly prevalent issue of suboptimal CHO
      consumption in the endurance sports realm.

PMID- 30217201
TI  - Severely malnourished children with a low weight-for-height have a higher
      mortality than those with a low mid-upper-arm-circumference: III. Effect of case
      load on malnutrition related mortality- policy implications.
AB  - BACKGROUND: Severe acute malnutrition (SAM) is diagnosed when the weight-for
      height Z-score (WHZ) is <-3Z of the WHO2006 standards, or a mid-upper-arm
      circumference (MUAC) of < 115 mm or there is nutritional oedema. Although there
      has been a move to eliminate WHZ as a diagnostic criterion we have shown that
      children with a low WHZ have at least as high a mortality risk as those with a
      low MUAC. Here we take the estimated case fatality rates and published case-loads
      to estimate the proportion of total SAM related deaths occurring in children that
      would be excluded from treatment with a MUAC-only policy. METHODS: The effect of
      varying case-load and mortality rates on the proportion of all deaths that would
      occur in admitted children was examined. We used the same calculations to
      estimate the proportion of all SAM-related deaths that would be excluded with a
      MUAC-only policy in 48 countries with very different relative case loads for SAM
      by only MUAC, only WHZ and children with both deficits. The case fatality rates
      (CFR) are taken from simulations, empirical data and the literature. RESULTS: The
      relative number of cases of SAM by MUAC alone, WHZ alone and those with both
      criteria have a dominant effect on the proportion of all SAM-related deaths that
      would occur in children excluded from treatment by a MUAC-only program. Many
      countries, particularly in the Sahel, West Africa and South East Asia would fail
      to identify the majority of SAM-related deaths if a MUAC only program were to be
      implemented. Globally, the estimated minimum number of deaths that would occur
      among children excluded from treatment in our analyses is 300,000 annually.
      CONCLUSIONS: The number, proportion or attributable fraction of children excluded
      from treatment with any change of current policy are the correct indicators to
      guide policy change. CRFs alone should not be used to guide policy in choosing
      whether or not to drop WHZ as a diagnostic for SAM. All the criteria for
      diagnosis of malnutrition need to be retained. It is critical that methods are
      found to identify those children with a low WHZ, but not a low MUAC, in the
      community so that they will not remain undetected.

PMID- 30217200
TI  - Assessing whether EORTC QLQ-30 and FACT-G measure the same constructs of quality
      of life in patients with total laryngectomy.
AB  - BACKGROUND: The European Organization for Research and Treatment of Cancer QOL
      Core Questionnaire 30 (EORTC QLQ-30) and the Assessment of Cancer Therapy-General
      (FACT-G) are the two most widely used measures of cancer-specific health-related
      quality of life (HRQOL). This study aims to assess whether the two instruments
      measure the same constructs of HRQOL in patients with total laryngectomy.
      METHODS: The EORTC QLQ-30 and the FACT-G was completed by 132 patients with total
      laryngectomy. Convergent, discriminant, and construct validity of the EORTC QLQ
      C30 and the FACT-G were assessed by Spearman's correlation and explanatory factor
      analysis. RESULTS: The results of factor analysis showed that the EORTC QLQ-C30
      and the FACT-G measure different aspects of HRQOL. Moreover, both instruments
      showed excellent convergent and discriminant validity, except for nausea and
      vomiting symptom subscale in the EORTC QLQ-C30 questionnaire. The internal
      consistency was close or greater than 0.7 for all domains of both instruments
      except for functional wellbeing in FACT-G. CONCLUSIONS: This study revealed that
      neither of the two instruments can be replaced by the other in the assessment of
      HRQOL in Iranian patients with total laryngectomy. Accordingly, clinicians should
      exactly define their research questions related to patient-reported outcomes
      before choosing which instrument to use.

PMID- 30217202
TI  - Identifying children at risk of malnutrition.

PMID- 30217203
TI  - Dietary intake of professional Australian football athletes surrounding body
      composition assessment.
AB  - BACKGROUND: Sports Dietitians aim to assist in improving performance by
      developing nutrition knowledge (NK), enhancing dietary intake and optimising body
      composition of athletes. In a high-pressure environment, it is important to
      identify factors that may compromise an athlete's nutrition status. Body
      composition assessments are regularly undertaken in sport to provide feedback on
      training adaptions; however, no research has explored the impact of these
      assessments on the dietary intake of professional athletes. METHODS: This cross
      sectional study assessed dietary intake (7-day food diary), nutrition knowledge
      (Nutrition for Sport Knowledge Questionnaire) and body composition (Dual-energy X
      ray absorptiometry) of 46 professional male Australian football (AFL) athletes
      during a 2017 pre-season training week (7 days) where body composition
      assessments were undertaken. Dietary intake was assessed against International
      Olympic Committee recommendations for professional athletes. RESULTS: Overall, no
      athlete met dietary their recommended energy intake (15 +/- 1.1 vs. 9.1 +/- 1.8
      MJ, respectively) or carbohydrate recommendations (6-10 vs. 2.4 +/- 0.9 g.kg
      1.day-1). Only 54% met protein recommendations. Secondary analyses demonstrated
      significant associations between education status and energy intake (P < 0.04)
      and vegetable intake (P < 0.03), with higher levels of education being associated
      with higher intakes. A moderately positive association was observed between NK
      scores and meeting estimated energy requirements (r = 0.33, P = 0.03). NK scores
      were also positively associated with protein (r = 0.35, P = 0.02), fibre (r =
      0.51, P = 0.001) and calcium intakes (r = 0.43, P = 0.004). CONCLUSIONS: This
      research identified that the dietary intake of professional AFL athletes during a
      pre-season training week where body composition assessments were undertaken did
      not meet current recommendations. Several factors may influence the dietary
      intake of AFL athletes, including lower education levels, poor NK and dietary
      intake restriction surrounding body composition assessment. Athletes may require
      support to continue with performance-based nutrition plans in periods surrounding
      body composition assessment.

PMID- 30217204
TI  - Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) adapted for use in adult
      patients: report from an initial validation study.
AB  - BACKGROUND: Localized scleroderma (LoS) affects both children and adults and is
      associated with permanent functional and cosmetic impairment, and reduced quality
      of life predominating in adults. The Localized Scleroderma Cutaneous Assessment
      Tool (LoSCAT) is a clinical instrument designed to measure an activity and damage
      of LoS. It has been validated for use with pediatric LoS patients. This study
      assessed the validity and reliability of the LoSCAT adapted for use in adults.
      METHODS: Before the initiation of the study two examiners participated in an
      intensive training course carried out by an expert in LoS. Appendices describing
      each LoSCAT domain were prepared. Features determining disease activity and
      damage in adult LoS patients were identified to properly evaluate the physician
      (Phys) and patient (Pt) global assessment (GA) of disease activity (A)/severity
      (S) and damage (D), which were used to assess convergent validity of the LoSCAT.
      Correlations of physician- and patient-derivied measures with Skindex-29 were
      also analysed. RESULTS: The study included 40 adult LoS patients (33 females and
      7 males) with different subtypes of LoS. Intra and inter-rater reliability of the
      LoSCAT was found to be excellent. Positive correlations were observed between the
      PhysGA-A, PhysGA-D, PtGA-A and the LoSCAT's domains, while no correlations
      between them and the PtGA-D were found. There were no relationships between
      LoSCAT's components and Skindex-29. CONCLUSIONS: Despite the LoSCAT is a reliable
      tool for an assessment of cutaneous lesions, additional health status instruments
      are necessary to a holistic approach to LoS in adults.

PMID- 30217205
TI  - Severely malnourished children with a low weight-for-height have a higher
      mortality than those with a low mid-upper-arm-circumference: I. Empirical data
      demonstrates Simpson's paradox.
AB  - BACKGROUND: According to WHO childhood severe acute malnutrition (SAM) is
      diagnosed when the weight-for-height Z-score (WHZ) is <-3Z of the WHO2006
      standards, the mid-upper-arm circumference (MUAC) is < 115 mm, there is
      nutritional oedema or any combination of these parameters. Recently there has
      been a move to eliminate WHZ as a diagnostic criterion on the assertion that
      children meeting the WHZ criterion are healthy, that MUAC is universally a
      superior prognostic indicator of mortality and that adding WHZ to the assessment
      does not improve the prediction; these assertions have lead to a controversy
      concerning the role of WHZ in the diagnosis of SAM. METHODS: We examined the
      mortality experience of 76,887 6-60 month old severely malnourished children
      admitted for treatment to in-patient, out-patient or supplementary feeding
      facilities in 18 African countries, of whom 3588 died. They were divided into 7
      different diagnostic categories for analysis of mortality rates by comparison of
      case fatality rates, relative risk of death and meta-analysis of the difference
      between children admitted using MUAC and WHZ criteria. RESULTS: The mortality
      rate was higher in those children fulfilling the WHO2006 WHZ criterion than the
      MUAC criterion. This was the case for younger as well as older children and in
      all regions except for marasmic children in East Africa. Those fulfilling both
      criteria had a higher mortality. Nutritional oedema increased the risk of death.
      Having oedema and a low WHZ dramatically increased the mortality rate whereas
      addition of the MUAC criterion to either oedema-alone or oedema plus a low WHZ
      did not further increase the mortality rate. The data were subject to extreme
      confounding giving Simpson's paradox, which reversed the apparent mortality rates
      when children fulfilling both WHZ and MUAC criteria were included in the
      estimation of the risk of death of those fulfilling either the WHZ or MUAC
      criteria alone. CONCLUSIONS: Children with a low WHZ, but a MUAC above the SAM
      cut-off point are at high risk of death. Simpson's paradox due to confounding
      from oedema and mathematical coupling may make previous statistical analyses
      which failed to distinguish the diagnostic groups an unreliable guide to policy.
      WHZ needs to be retained as an independent criterion for diagnosis of SAM and
      methods found to identify those children with a low WHZ, but not a low MUAC, in
      the community.

PMID- 30217206
TI  - The interpretation of change score of the pain disability index after vocational
      rehabilitation is baseline dependent.
AB  - BACKGROUND: The Pain Disability Index (PDI) is a widely-used instrument to
      measure pain-related disability. The aim of this study was to assess the
      responsiveness and interpretation of change score of the PDI in patients with
      chronic musculoskeletal pain (CMP) at discharge of vocational rehabilitation.
      METHODS: Retrospective data of patients with CMP who attended vocational
      rehabilitation between 2014 and 2017 was used. The anchor-based method was used
      to assess the responsiveness of the total sample and of PDI baseline quartile
      groups. A receiver operating characteristic curve was performed, including Area
      Under the Curve (AUC) and Minimal Important Change (MIC). RESULTS: The PDI showed
      responsive to detect clinically relevant changes in pain-related disability at
      discharge of vocational rehabilitation (AUC 0.79). A PDI change score of 13
      points (MIC 12.5) can be considered as a real change in pain-related disability
      for the total study sample, and a PDI change score of 7-20 points can be
      considered as a real change in pain-related disability for PDI lowest and highest
      baseline quartile scores. CONCLUSION: The PDI is responsive in patients with CMP
      at discharge of vocational rehabilitation. The interpretation of change score
      depends on PDI baseline score. Patients with a PDI baseline score of <=27 should
      decrease minimal 7 points, patients with a baseline score between 28 and 42
      should decrease minimal 15 points, and patients with a baseline score >= 43
      should decrease minimal 20 points.

PMID- 30217207
TI  - Spatial analyzes of HLA data in Rio Grande do Sul, south Brazil: genetic
      structure and possible correlation with autoimmune diseases.
AB  - BACKGROUND: HLA genes are the most polymorphic of the human genome and have
      distinct allelic frequencies in populations of different geographical regions of
      the world, serving as genetic markers in ancestry studies. In addition, specific
      HLA alleles may be associated with various autoimmune and infectious diseases.
      The bone marrow donor registry in Brazil is the third largest in the world, and
      it counts with genetic typing of HLA-A, -B, and -DRB1. Since 1991 Brazil has
      maintained the DATASUS database, a system fed with epidemiological and health
      data from compulsory registration throughout the country. METHODS: In this work,
      we perform spatial analysis and georeferencing of HLA genetic data from more than
      86,000 bone marrow donors from Rio Grande do Sul (RS) and data of hospitalization
      for rheumatoid arthritis, multiple sclerosis and Crohn's disease in RS,
      comprising the period from 1995 to 2016 obtained through the DATASUS system. The
      allele frequencies were georeferenced using Empirical Bayesian Kriging; the
      diseases prevalence were georeferenced using Inverse Distance Weighted and
      cluster analysis for both allele and disease were performed using Getis-Ord Gi*
      method. Spearman's test was used to test the correlation between each allele and
      disease. RESULTS: The results indicate a HLA genetic structure compatible with
      the history of RS colonization, where it is possible to observe differentiation
      between regions that underwent different colonization processes. Spatial analyzes
      of autoimmune disease hospitalization data were performed revealing clusters for
      different regions of the state for each disease analyzed. The correlation test
      between allelic frequency and the occurrence of autoimmune diseases indicated a
      significant correlation between the HLA-B*08 allele and rheumatoid arthritis.
      CONCLUSIONS: Genetic mapping of populations and the spatial analyzes such as
      those performed in this work have great economic relevance and can be very useful
      in the formulation of public health campaigns and policies, contributing to the
      planning and adjustment of clinical actions, as well as informing and educating
      professionals and the population.

PMID- 30217208
TI  - Evaluation of cell-surface displayed synthetic consensus dengue EDIII cells as a
      potent oral vaccine candidate.
AB  - BACKGROUND: Dengue is a rapidly spreading mosquito borne tropical viral disease
      affecting hundreds of millions of people across the globe annually. The dengue
      virus (DENV) includes four genetically distinct serotypes that cause serious life
      threatening infections, including dengue hemorrhagic fever/dengue shock syndrome.
      Dengue vaccine development is complicated by the possibility of vaccine-enhanced
      severe dengue disease due to antibody-dependent enhancement by pre-existing cross
      reactivity, as well as homotypic antibodies. Thus, the development of an
      efficacious dengue vaccine conferring simultaneous and durable immunity to each
      of the four DENV serotypes has not yet been developed despite years of research.
      For mass immunization in deeply affected resource-limited countries, oral
      vaccination is considered more beneficial than conventional approaches.
      Therefore, in a continuing effort towards designing economical and potent vaccine
      candidates, the current study applied yeast surface display technology to develop
      an oral dengue vaccine candidate using whole recombinant yeast cells displaying
      the recombinant fusion protein of M cell targeting ligand Co1 fused to the
      synthetic consensus dengue envelope domain III (scEDIII). Female Balb/c mice were
      orally fed with recombinant yeast cells and immunogenicity in terms of systemic
      and mucosal immune responses was monitored. RESULTS: Immunofluorescence
      microscopy with dengue specific antibody and fluorescein isothiocyanate
      conjugated anti-mouse IgG antibody clearly showed that recombinant protein Co1
      scEDIII-AGA was localized on the cell surface of the respective clones in
      comparison with scEDIII-Co1 and Mock cells with no fluorescence. Oral dosage
      applications of surface displayed Co1-scEDIII-AGA stimulated a systemic humoral
      immune response in the form of dengue-specific serum IgG, as well as a mucosal
      immune response in the form of secretory immunoglobulin A (sIgA). Antigen
      specific B cell responses in isolated lymphoid cells from the spleen and Peyer's
      patches further supported an elevated mucosal immune response. In addition,
      surface displayed Co1-scEDIII-AGA feeding elicited strong immune responses in
      comparison with scEDIII-Co1 and Mock following intraperitoneal booster with
      purified scEDIII antigen. CONCLUSIONS: Surface displayed preparations of Co1
      scEDIII-AGA induced strong immunogenicity compared with non-displayed scEDIII
      Co1. Prior studies have supported the neutralization potential of scEDIII
      constructs against all four serotypes. Thus, the oral administration of
      genetically engineered yeast whole cells displaying biologically active Co1
      scEDIII fusion protein without any further processing shows prospective as a
      potent oral vaccine candidate against dengue viral infection.

PMID- 30217209
TI  - Mild ovarian stimulation with letrozole plus fixed dose human menopausal
      gonadotropin prior to IVF/ICSI for infertile non-obese women with polycystic
      ovarian syndrome being pre-treated with metformin: a pilot study.
AB  - BACKGROUND: Letrozole is widely employed as ovulation induction agent in women
      with PCOS, but its use in mild stimulation (MS) protocols for IVF is limited. Aim
      of the present study was to evaluate the feasibility of a MS protocol with
      letrozole plus hMG in non-obese PCOS women undergoing IVF after a metformin pre
      treatment. METHODS: We retrospectively evaluated the data of 125 non-obese PCOS
      undergoing MS with letrozole plus hMG, 150 IU as starting dose, (group 1, N = 80)
      compared to those undergoing a conventional IVF stimulation protocols (CS) (group
      2, N = 45) prior to IVF. All patients had received metformin extended release
      1200-2000 mg daily for three to six months before IVF. GnRH antagonist was
      administered in both groups when the leading follicles reached 14 mm. RESULTS:
      Both groups were comparable for age, BMI and ovarian reserve markers. Both groups
      showed lower than expected AFC and AMH values as a consequence of metformin pre
      treatment. Letrozole-treated patients required a significantly lower amount of
      gonadotropins units (p < 0.0001), and showed significantly lower day 5, day 8 and
      hCG day E2 levels compared to patients undergoing the CS protocol (p < 0.0001, p
      < 0.0001 and p = 0.001 respectively). The oocyte yield, in terms of total (6, IQR
      3, vs 6, IQR 4 respectively,) and MII oocytes (5, IQR 3, vs 5, IQR 3,
      respectively) number, did not differ among groups; the number of total (3, IQR 2,
      vs 3, IQR 1 respectively) and good quality embryos (2, IQR1 vs 2, IQR 1,5
      respectively) obtained was comparable as well in the two groups. The number of
      fresh transfers was significantly higher in group 1 compared to group 2 (80% vs
      60%, p = 0.016). A trend for higher cumulative clinical pregnancy rate was found
      in women undergoing MS compared to CS (42.5%vs 24,4%, p = 0.044), but the study
      was not powered to detect this difference. CONCLUSIONS: The present study
      suggests that the use of letrozole as adjuvant treatment to MS protocols for IVF
      may be an effective alternative to CS protocols for non-obese PCOS patients pre
      treated with metformin, as it provides comparable IVF outcome without requiring
      high FSH dose, and avoiding supraphysiological estradiol levels.

PMID- 30217210
TI  - Physical activity equivalent labeling vs. calorie labeling: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Many countries are trying to identify strategies to control obesity.
      Nutrition labeling is a policy that could lead to healthy food choices by
      providing information to consumers. Calorie labeling, for example, could lead to
      consumers choosing lower calorie foods. However, its effectiveness has been
      limited. Recently, physical activity equivalent labeling (i.e., displaying
      calories in terms of estimated amount of physical activity to burn calories) has
      been proposed as an alternative to the calorie-only label. The aim of this review
      was to identify and evaluate the published literature comparing effects on health
      behavior between physical activity equivalent labeling and calorie-only labeling.
      METHOD: We searched the following databases: Pubmed/medline, Scopus, Web of
      science, Agris, Cochrane library, Google Scholar. We also searched along with
      reference lists of included articles. Articles that were published between 1
      January 2000 and 31 October 2016 were eligible for inclusion provided they
      reported on studies that examined the effects of both types of labeling and
      included at least one outcome of interest. Mean and standard deviations of the
      included results were combined using a fixed-effect model. The difference in
      calories purchased between people exposed to physical activity labeling and
      calorie-only labeling was calculated as weighted mean difference by using a fixed
      effect model. RESULT: The difference of calories ordered between physical
      activity label and calorie label groups was not statistically significant (SMD: 
      0.03; 95% CI: -0.13, 0.07). The difference of calories ordered between physical
      activity label and calorie label according to real vs unreal (e.g. web-based)
      condition was 65 Kcal fewer in real-world settings. CONCLUSION: Physical activity
      calorie equivalent labeling in minutes does not significantly reduce calories
      ordered compared to calorie-only labeling.

PMID- 30217212
TI  - How do we deliver our findings? Analysis of podium presentations at shoulder
      meetings.
AB  - BACKGROUND: The aim of the present study was to evaluate the time structure of
      oral presentations delivered at three shoulder congresses: shoulder sessions at
      the American Academy of Orthopaedic Surgeons (AAOS) Meeting, European Foundation
      of National Associations of Orthopaedics and Traumatology (EFORT) Congress, and
      International Congress of Shoulder and Elbow Surgery (ICSES). METHODS: A total of
      160 oral presentations at the 2016 AAOS Annual Meeting, 17th EFORT Congress, and
      13th ICSES were included. Podium presentations were categorized by topic,
      congress, inclusion of video support, and nationality of the speaker. Total time
      and time dedicated to each section of the presentation (introduction, methods,
      results, discussion and conclusions) were collected for all podium presentations.
      RESULTS: Approximately 34% of speakers exceeded time constraints. No differences
      were found in the times that presenters used for the introduction, methods,
      results, and conclusions sections (p > 0.05). However, when extended
      introductions were delivered, the results and conclusions sections were shortened
      (r = - 0.2 and r = - 0.21, respectively). Inclusion of video support tended to
      result in exceedance of time limits (p < 0.01). CONCLUSIONS: One third of the
      shoulder surgeons exceeded time constraints in their conference presentations,
      and no distinctions were found in time allocations for different sections of the
      presentations. Longer introductions may lead to time restriction in the results
      and conclusions sections.

PMID- 30217211
TI  - Performance management in times of change: experiences of implementing a
      performance assessment system in a district in South Africa.
AB  - BACKGROUND: Health systems globally are under pressure to ensure value for money,
      and the people working within the system determine the extent and nature of
      health services provided. A performance assessment (PA); an important component
      of a performance management system (PMS) is deemed important at improving the
      performance of human resources for health. An effective PA motivates and improves
      staff engagement in their work. The aim of this paper is to describe the
      experiences of implementing a PA practice at a district in South Africa. It
      highlights factors that undermine the intention of the process and reflects on
      factors that can enable implementation to improve the staff performance for an
      effective and efficient district health service. METHODS: Data was collected
      through in-depth interviews, observations and reflective engagements with
      managers at a district in one of the Provinces in South Africa. The study
      examined the managers' experiences of implementing the PA at the district level.
      RESULTS: Findings illuminate that a range of factors influence the implementation
      of the PA system. Most of it is attributed to context and organizational culture
      including management and leadership capacity. The dominance of autocratic
      approaches influence management and supervision of front-line managers.
      Management and leadership capacity is constrained by factors such as insufficient
      management skills due to lack of training. The established practice of recruiting
      from local communities facilitates patronage - compromising supervisor
      subordinate relationships. In addition, organizational constraints and the
      constant policy changes and demands have compromised the implementation of the
      overall Performance Management and Development System (PMDS) - indirectly
      affecting the assessment component. CONCLUSION: To strengthen district health
      services, there should be improvement of processes that enhance the performance
      of the health system. Implementation of the PA system relies on the extent of
      management skills at the local level. There is a need to develop managers who
      have the ability to manage in a transforming and complex environment. This means
      developing both hard skills such as planning, co-ordination and monitoring and
      soft skills where one is able to focus on relationships and communication,
      therefore allowing collaborative and shared management as opposed to
      authoritarian approaches.

PMID- 30217213
TI  - Secondary findings in 421 whole exome-sequenced Chinese children.
AB  - BACKGROUND: Variants with known or possible pathogenicity located in genes that
      are unrelated to primary disease conditions are defined as secondary findings.
      Secondary findings are not the primary targets of whole exome and genome
      sequencing (WES/WGS) assay but can be of great practical value in early disease
      prevention and intervention. The driving force for this study was to investigate
      the impact of racial difference and disease background on secondary findings.
      Here, we analyzed secondary findings frequencies in 421 whole exome-sequenced
      Chinese children who are phenotypically normal or bear congenital heart
      diseases/juvenile obesity. In total, 421 WES datasets were processed for
      potential deleterious variant screening. A reference gene list was defined
      according to the American College of Medical Genetics and Genomics (ACMG)
      recommendations for reporting secondary findings v2.0 (ACMG SF v2.0). The variant
      classification was performed according to the evidence-based guidelines
      recommended by the joint consensus of the ACMG and the Association for Molecular
      Pathology (AMP). RESULTS: Among the 421 WES datasets, we identified 11
      known/expected pathogenic variants in 12 individuals, accounting for 2.85% of our
      samples, which is much higher than the reported frequency in a Caucasian
      population. In conclusion, secondary findings are not so rare in Chinese
      children, which means that we should pay more attention to the clinical
      interpretation of sequencing results.

PMID- 30217214
TI  - Nivolumab induced encephalopathy in a man with metastatic renal cell cancer: a
      case report.
AB  - BACKGROUND: Great progress has recently been made in the treatment of metastatic
      renal cell carcinoma, including the introduction of nivolumab, an immune
      checkpoint inhibitor. Despite promising results, this treatment brings a
      completely new spectrum of adverse events, distinct from those experienced with
      small-molecule kinase inhibitors. Neurologic immune-related adverse events may be
      serious and potentially life-threatening complications requiring immediate
      immunosuppressive therapy. Only a few cases of immune-related encephalitis
      induced by checkpoint inhibitors have been described and the data regarding the
      management of this serious adverse event are limited. CASE PRESENTATION: We
      report the case of a 63-year-old white man with metastatic renal cancer who
      developed severe chorea-like dyskinesia during nivolumab therapy. The findings on
      brain magnetic resonance imaging and flow cytometry of cerebrospinal fluid, and
      the positivity of anti-paraneoplastic antigen Ma2 immunoglobuline G class
      autoantibodies were consistent with a diagnosis of immune-related encephalitis.
      High-dose intravenous corticosteroid therapy was started immediately, with no
      signs of improvement, even when infliximab was added. Our patient refused further
      hospitalization and was discharged. Three weeks later, he presented with signs of
      severe urosepsis. Despite intensive treatment, he died 4 days after admission.
      CONCLUSIONS: The management of less frequent immune-related adverse events has
      not been fully established and more information is required to provide uniform
      recommendations. Immune-related encephalitis is a severe and potentially fatal
      complication requiring immediate hospital admission and extensive
      immunosuppressive therapy. The examination of cerebrospinal fluid for
      paraneoplastic antibodies, such as anti-N-methyl-D-aspartate receptor and anti
      Ma2 antibodies, in order to distinguish autoimmune etiology from other possible
      causes is essential and highly recommended.

PMID- 30217215
TI  - One-year mortality in displaced intracapsular hip fractures and associated risk:
      a report of Chinese-based fragility fracture registry.
AB  - BACKGROUND: The purpose of this registry-based retrospective study was to
      investigate the risk factors related to one-year mortality in displaced
      intracapsular fragility hip fracture patients. METHODS: Patients were screened
      from the Fragility Fracture Registry. Inclusion criterion was displaced
      intracapsular hip fracture patients with atypical or pathological fractures
      excluded. One-year mortality was investigated against risk factors including age,
      gender, past medical history, pre-fracture mobility (PFM), pre-operation ASA
      grade, delayed surgery over 48 h, post-surgical complications, and length of stay
      at acute orthopedic ward (LOS). RESULTS: A total of 1050 patients were included
      for further analysis. Gross one-year mortality was 14.9%. One-year mortality was
      significantly higher in patients who received non-operative treatment and those
      who received surgery but delayed over 48 h after admission (both p <  0.001).
      Male gender (OR = 2.708), advanced age (OR = 1.359), higher risk ASA grades (III
      to V) (OR = 1.990), past history of gastrointestinal disease (OR = 1.671), and
      renal impairment (OR = 1.984) were related to higher one-year mortality. The
      mortality of patients in PFM grade 3 and LOS group 3 was significantly higher (OR
      = 2.240 and 1.722, respectively). CONCLUSIONS: Higher age, male gender, past
      gastrointestinal disease and renal impairment, ASA grade over 3, indoor confined
      pre-fracture ambulatory, and stay at hospital over 15 days were risk factors
      related to higher one-year mortality in surgically treated displaced
      intracapsular hip fracture patients. A multi-disciplinary approach is advised to
      patients identified with these risks factors and co-managed by orthopedic
      surgeons, geriatricians, and fracture liaison nurses.

PMID- 30217216
TI  - Study protocol for single-center, open-label, randomized controlled trial to
      clarify the preventive efficacy of electrical stimulation for muscle atrophy
      after trauma.
AB  - BACKGROUND: Management of trauma involves long-term bed rest even when muscle
      strength in the lower extremities is preserved. Prolonged bed rest reduces muscle
      mass and causes muscle atrophy. A recent study reported the efficacy of
      rehabilitation using electrical muscle stimulation (EMS) for muscle strength
      maintenance in intensive care unit patients with disturbance of consciousness.
      However, despite the expected benefits of EMS in maintaining muscle strength,
      little is known about its efficacy in trauma patients. METHODS/DESIGN: A single
      center, open-label, randomized controlled trial of 40 patients with pelvic
      fracture to test the effectiveness of 14 days of EMS. The primary outcome will be
      change in cross-sectional area of the thigh muscle between pre and post
      intervention, as measured on computed tomography images. We will analyze the
      primary endpoint by analysis of covariance (ANCOVA) and analyze the secondary
      endpoints in an exploratory manner. CONCLUSION: If our hypothesis is confirmed,
      this study will provide evidence that the use of EMS can be effective in
      preventing muscle atrophy. TRIAL REGISTRATION: UMIN registration number:
      UMIN000030190 . Registered on 1 December 2017.

PMID- 30217218
TI  - Overexpression of CLC-3 is regulated by XRCC5 and is a poor prognostic biomarker
      for gastric cancer.
AB  - BACKGROUND: Recently, many potential prognostic biomarkers for gastric cancer
      (GC) have been identified, but the prognosis of advanced GC patients remains
      poor. Chloride channels are promising cancer biomarkers, and their family member
      chloride channel-3 (CLC-3) is involved in multiple biological behaviors. However,
      whether CLC-3 is a prognostic biomarker for GC patients is rarely reported. The
      molecular mechanisms by which CLC-3 is regulated in GC are unclear. METHODS: The
      expression of CLC-3 and XRCC5 in human specimens was analyzed using
      immunohistochemistry. The primary biological functions and pathways related to
      CLC-3 were enriched by RNA sequencing. A 5'-biotin-labeled DNA probe with a
      promoter region between - 248 and + 226 was synthesized to pull down CLC-3
      promoter-binding proteins. Functional studies were detected by MTS, clone
      formation, wound scratch, transwell, and xenograft mice model. Mechanistic
      studies were investigated by streptavidin-agarose-mediated DNA pull-down, mass
      spectrometry, ChIP, dual-luciferase reporter assay system, Co-IP, and
      immunofluorescence. RESULTS: The results showed that CLC-3 was overexpressed in
      human GC tissues and that overexpression of CLC-3 was a poor prognostic biomarker
      for GC patients (P = 0.012). Furthermore, higher expression of CLC-3 was
      correlated with deeper tumor invasion (P = 0.006) and increased lymph node
      metastasis (P = 0.016), and knockdown of CLC-3 inhibited cell proliferation and
      migration in vitro. In addition, X-ray repair cross-complementing 5 (XRCC5) was
      identified as a CLC-3 promoter-binding protein, and both CLC-3 (HR 1.671; 95% CI
      1.012-2.758; P = 0.045) and XRCC5 (HR 1.795; 95% CI 1.076-2.994; P = 0.025) were
      prognostic factors of overall survival in GC patients. The in vitro and in vivo
      results showed that the expression and function of CLC-3 were inhibited after
      XRCC5 knockdown, and the inhibition effects were rescued by CLC-3 overexpression.
      Meanwhile, the expression and function of CLC-3 were promoted after XRCC5
      overexpression, and the promotion effects were reversed by the CLC-3 knockdown.
      The mechanistic study revealed that knockdown of XRCC5 suppressed the binding of
      XRCC5 to the CLC-3 promoter and subsequent promoter activity, thus regulating CLC
      3 expression at the transcriptional level by interacting with PARP1. CONCLUSIONS:
      Our findings indicate that overexpression of CLC-3 is regulated by XRCC5 and is a
      poor prognostic biomarker for gastric cancer. Double targeting CLC-3 and XRCC5
      may provide the promising therapeutic potential for GC treatment.

PMID- 30217219
TI  - Diverse model systems reveal common principles of meiosis.
AB  - A meeting report on the 14th Gordon Research Conference on Meiosis, held at Colby
      Sawyer College, New London, NH, USA, 9-15 June 2018, chaired by Monica
      Colaiacovo, Harvard Medical School.

PMID- 30217217
TI  - The roles of tumor-derived exosomes in non-small cell lung cancer and their
      clinical implications.
AB  - Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer
      cases, and it is one of the leading causes of cancer death in both men and women
      worldwide due to diagnosis in the advanced stage, rapid metastasis, and
      recurrence. At present, precision molecular targeted therapeutics directed toward
      NSCLC driven genes has made great progress and significantly improved the overall
      survival of patients with NSCLC, but can easily lead to acquired drug resistance.
      New methods are needed to develop real-time monitoring of drug efficacy and drug
      resistance, such as new molecular markers for more effective early detection and
      prediction of prognosis. Exosomes are nano-sized extracellular vesicles,
      containing proteins, nucleic acids and lipids, which are secreted by various
      cells, and they play an important role in the development of lung cancer by
      controlling a wide range of pathways. Tumor-derived exosomes are of great
      significance for guiding the targeted therapy of NSCLC and exosomes themselves
      can be a target for treatment. In this review, we describe the potential roles of
      tumor-derived exosomes and their clinical significance in NSCLC.

PMID- 30217220
TI  - Alternative splicing links histone modifications to stem cell fate decision.
AB  - BACKGROUND: Understanding the embryonic stem cell (ESC) fate decision between
      self-renewal and proper differentiation is important for developmental biology
      and regenerative medicine. Attention has focused on mechanisms involving histone
      modifications, alternative pre-messenger RNA splicing, and cell-cycle
      progression. However, their intricate interrelations and joint contributions to
      ESC fate decision remain unclear. RESULTS: We analyze the transcriptomes and
      epigenomes of human ESC and five types of differentiated cells. We identify
      thousands of alternatively spliced exons and reveal their development and lineage
      dependent characterizations. Several histone modifications show dynamic changes
      in alternatively spliced exons and three are strongly associated with 52.8% of
      alternative splicing events upon hESC differentiation. The histone modification
      associated alternatively spliced genes predominantly function in G2/M phases and
      ATM/ATR-mediated DNA damage response pathway for cell differentiation, whereas
      other alternatively spliced genes are enriched in the G1 phase and pathways for
      self-renewal. These results imply a potential epigenetic mechanism by which some
      histone modifications contribute to ESC fate decision through the regulation of
      alternative splicing in specific pathways and cell-cycle genes. Supported by
      experimental validations and extended datasets from Roadmap/ENCODE projects, we
      exemplify this mechanism by a cell-cycle-related transcription factor, PBX1,
      which regulates the pluripotency regulatory network by binding to NANOG. We
      suggest that the isoform switch from PBX1a to PBX1b links H3K36me3 to hESC fate
      determination through the PSIP1/SRSF1 adaptor, which results in the exon skipping
      of PBX1. CONCLUSION: We reveal the mechanism by which alternative splicing links
      histone modifications to stem cell fate decision.

PMID- 30217222
TI  - Influencing medical student choice of primary care worldwide: international
      application of the four pillars for primary care physician workforce.
AB  - Primary care is a crucial part of a functional health care system, though in many
      parts of the world there are current or projected gaps in the primary care
      physician workforce. The academic family medicine organizations in the United
      States (US) developed the "Four Pillars for Primary Care Physician Workforce," a
      model built on decades of research, highlighting four main areas of emphasis for
      increasing primary care physician output: 1) pipeline; 2) process of medical
      education; 3) practice transformation; and 4) payment reform. This commentary
      proposes that this model, although developed in the US context, is applicable in
      other medical education settings, including Israel, based on the recently
      reported findings of Weissman and colleagues in this journal.

PMID- 30217223
TI  - Linking cell function with perfusion: insights from the transcatheter delivery of
      bone marrow-derived CD133+ cells in ischemic refractory cardiomyopathy trial
      (RECARDIO).
AB  - BACKGROUND: Cell therapy with bone marrow (BM)-derived progenitors has emerged as
      a promising therapeutic for refractory angina (RA) patients. In the present
      study, we evaluated the safety and preliminary efficacy of transcatheter delivery
      of autologous BM-derived advanced therapy medicinal product CD133+ cells (ATMP
      CD133) in RA patients, correlating perfusion outcome with cell function. METHODS:
      In the phase I "Endocavitary Injection of Bone Marrow Derived CD133+ Cells in
      Ischemic Refractory Cardiomyopathy" (RECARDIO) trial, a total of 10 patients with
      left ventricular (LV) dysfunction (ejection fraction <= 45%) and evidence of
      reversible ischemia, as assessed by single-photon emission computed tomography
      (SPECT), underwent BM aspiration and fluoroscopy-based percutaneous
      endomyocardial delivery of ATMP-CD133. Patients were evaluated at 6 and 12 months
      for safety and preliminary efficacy endpoints. ATMP-CD133 samples were used for
      in vitro correlations. RESULTS: Patients were treated safely with a mean number
      of 6.57 +/- 3.45 *  106 ATMP-CD133. At 6-month follow-up, myocardial perfusion at
      SPECT was significantly ameliorated in terms of changes in summed stress (from
      18.2 +/- 8.6 to 13.8 +/- 7.8, p = 0.05) and difference scores (from 12.0 +/- 5.3
      to 6.1 +/- 4.0, p = 0.02) and number of segments with inducible ischemia (from
      7.3 +/- 2.2 to 4.0 +/- 2.7, p = 0.003). Similarly, Canadian Cardiovascular
      Society and New York Heart Association classes significantly improved at follow
      up vs baseline (p <= 0.001 and p = 0.007, respectively). Changes in summed stress
      score changes positively correlated with ATMP-CD133 release of proangiogenic
      cytokines HGF and PDGF-bb (r = 0.80, p = 0.009 and r = 0.77, p = 0.01,
      respectively) and negatively with the proinflammatory cytokines RANTES (r = -
      0.79, p = 0.01) and IL-6 (r = - 0.76, p = 0.02). CONCLUSION: Results of the
      RECARDIO trial suggested safety and efficacy in terms of clinical and perfusion
      outcomes in patients with RA and LV dysfunction. The observed link between
      myocardial perfusion improvements and ATMP-CD133 secretome may represent a proof
      of concept for further mechanistic investigations. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02059681 . Registered 11 February 2014.

PMID- 30217221
TI  - Regulation of PTEN expression by noncoding RNAs.
AB  - Phosphatase and tensin homologue (PTEN) triggers a battery of intracellular
      signaling pathways, especially PI3K/Akt, playing important roles in the
      pathogenesis of multiple diseases, such as cancer, neurodevelopmental disorders,
      cardiovascular dysfunction and so on. Therefore PTEN might be a biomarker for
      various diseases, and targeting the abnormal expression level of PTEN is
      anticipated to offer novel therapeutic avenues. Recently, noncoding RNAs (ncRNAs)
      have been reported to regulate protein expression, and it is definite that PTEN
      expression is controlled by ncRNAs epigenetically or posttranscriptionally as
      well. Herein, we provide a review on current understandings of the regulation of
      PTEN by ncRNAs, which could contribute to the development of novel approaches to
      the diseases with abnormal expression of PTEN.

PMID- 30217224
TI  - TIPE3 hypermethylation correlates with worse prognosis and promotes tumor
      progression in nasopharyngeal carcinoma.
AB  - BACKGROUND: Increasing evidence recognizes that DNA methylation abnormalities
      play critical roles in cancer development. Our previous genome-wide methylation
      profile showed that tumor necrosis factor-alpha-induced protein 8 like 3 (TIPE3)
      was hypermethylated in nasopharyngeal carcinoma (NPC). However, the relationship
      between TIPE3 methylation and its mRNA expression, as well as its biological
      roles in NPC are unknown. METHODS: Bisulfite pyrosequencing and quantitative RT
      PCR were performed to quantify the TIPE3 methylation and expression levels.
      Kaplan-Meier curves and Cox regression analysis were used to estimate the
      correlation between TIPE3 methylation levels and survival in two patient cohorts
      collected from two hospitals (n = 441). The MTT, colony formation, Transwell
      migration and invasion assays, and xenograft tumor growth and lung metastatic
      colonization models were used to identify the functions of TIPE3 on NPC cells.
      RESULTS: We found that TIPE3 CpG island (CGI) was hypermethylated and its mRNA
      levels were downregulated in many cancers, including NPC. TIPE3 downregulation
      was associated with its CGI hypermethylation. Furthermore, NPC patients with high
      TIPE3 CGI methylation levels had poorer clinical outcomes than those with low
      methylation levels. The TIPE3 CGI methylation level was an independent prognostic
      factor. Moreover, restoring TIPE3 expression significantly inhibited NPC cell
      proliferation, migration and invasion in vitro, and suppressed tumor growth and
      lung metastatic colonization in vivo, while silencing TIPE3 acted in an opposite
      way. CONCLUSIONS: TIPE3 downregulation correlates with its CGI hypermethylation
      in several solid cancers. TIPE3 acts as a tumor suppressor in NPC, providing a
      further insight into NPC progression and representing a potential prognostic
      biomarker for NPC.

PMID- 30217227
TI  - Clinical evaluation of modified transalveolar sinus floor elevation and osteotome
      sinus floor elevation in posterior maxillae: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Implant placement in the posterior maxilla is often complicated by
      the insufficient bone volume. While transalveolar sinus floor elevation (TSFE)
      has been proven as a predictable surgical procedure to increase the bone height
      in the posterior maxilla, questions in regard to the necessity of the bone
      grafting during the sinus lift and the question of whether TSFE could be
      performed when the residual bone height is below 5 mm are still debated.
      Furthermore, high-quality evidence comparing the clinical outcome of
      transalveolar sinus floor elevation with osteotome and modified sinus floor
      elevation with crestal non-cutting drills is limited. METHODS/DESIGN: One hundred
      twenty adult patients who fit the inclusion criteria are being recruited from the
      Peking University Hospital of Stomatology First Clinical Division (Beijing,
      China). All patients are assigned to one of four groups according to a table of
      random numbers. Participants will receive (1) TSFE using osteotomes with bone
      grafting, (2) TSFE using osteotomes without bone grafting, (3) modified TSFE with
      bone grafting, or (4) modified TSFE without bone grafting. In a one-year follow
      up period, implant survival rates, complications, implant stability, bone
      remodeling around the implant, and patient-reported outcome (visual analog scale
      for intraoperative discomfort and postoperative pain) will be observed and
      documented. The implant stability will be gauged by the resonance frequency
      analysis six times (at baseline and weeks 6, 8, 12, 16, and 26), and the bone
      remodeling will be observed and compared via radiographic examinations.
      DISCUSSION: The result of the trial will potentially contribute to better
      decision making in atrophic posterior maxilla when implant placement is needed.
      Therefore, if the outcome is deemed favorable, the use of the modified TSFE would
      achieve an outcome equivalent to that of the traditional TSFE while introducing
      less trauma and postoperative discomforts. Separately, whether the bone graft
      procedure is necessary for the TSFE will also be discussed. TRIAL REGISTRATION:
      The study has been registered in ClinicalTrials.gov under the identifier number
      NCT03445039 . Registered on 26 February 2018.

PMID- 30217226
TI  - Exome-wide analysis of bi-allelic alterations identifies a Lynch phenotype in The
      Cancer Genome Atlas.
AB  - BACKGROUND: Cancer susceptibility germline variants generally require somatic
      alteration of the remaining allele to drive oncogenesis and, in some cases, tumor
      mutational profiles. Whether combined germline and somatic bi-allelic alterations
      are universally required for germline variation to influence tumor mutational
      profile is unclear. Here, we performed an exome-wide analysis of the frequency
      and functional effect of bi-allelic alterations in The Cancer Genome Atlas
      (TCGA). METHODS: We integrated germline variant, somatic mutation, somatic
      methylation, and somatic copy number loss data from 7790 individuals from TCGA to
      identify germline and somatic bi-allelic alterations in all coding genes. We used
      linear models to test for association between mono- and bi-allelic alterations
      and somatic microsatellite instability (MSI) and somatic mutational signatures.
      RESULTS: We discovered significant enrichment of bi-allelic alterations in
      mismatch repair (MMR) genes and identified six bi-allelic carriers with elevated
      MSI, consistent with Lynch syndrome. In contrast, we find little evidence of an
      effect of mono-allelic germline variation on MSI. Using MSI burden and bi-allelic
      alteration status, we reclassify two variants of unknown significance in MSH6 as
      potentially pathogenic for Lynch syndrome. Extending our analysis of MSI to a set
      of 127 DNA damage repair (DDR) genes, we identified a novel association between
      methylation of SHPRH and MSI burden. CONCLUSIONS: We find that bi-allelic
      alterations are infrequent in TCGA but most frequently occur in BRCA1/2 and MMR
      genes. Our results support the idea that bi-allelic alteration is required for
      germline variation to influence tumor mutational profile. Overall, we demonstrate
      that integrating germline, somatic, and epigenetic alterations provides new
      understanding of somatic mutational profiles.

PMID- 30217225
TI  - Genomic analysis of transcriptional networks directing progression of cell states
      during MGE development.
AB  - BACKGROUND: Homeodomain (HD) transcription factor (TF) NKX2-1 critical for the
      regional specification of the medial ganglionic eminence (MGE) as well as
      promoting the GABAergic and cholinergic neuron fates via the induction of TFs
      such as LHX6 and LHX8. NKX2-1 defines MGE regional identity in large part through
      transcriptional repression, while specification and maturation of GABAergic and
      cholinergic fates is mediated in part by transcriptional activation via TFs such
      as LHX6 and LHX8. Here we analyze the signaling and TF pathways, downstream of
      NKX2-1, required for GABAergic and cholinergic neuron fate maturation. METHODS:
      Differential ChIP-seq analysis was used to identify regulatory elements (REs)
      where chromatin state was sensitive to change in the Nkx2-1cKO MGE at embryonic
      day (E) 13.5. TF motifs in the REs were identified using RSAT. CRISPR-mediated
      genome editing was used to generate enhancer knockouts. Differential gene
      expression in these knockouts was analyzed through RT-qPCR and in situ
      hybridization. Functional analysis of motifs within hs623 was analyzed via site
      directed mutagenesis and reporter assays in primary MGE cultures. RESULTS: We
      identified 4782 activating REs (aREs) and 6391 repressing REs (rREs) in the Nkx2
      1 conditional knockout (Nkx2-1cKO) MGE. aREs are associated with basic-Helix-Loop
      Helix (bHLH) TFs. Deletion of hs623, an intragenic Tcf12 aRE, caused a reduction
      of Tcf12 expression in the sub-ventricular zone (SVZ) and mantle zone (MZ) of the
      MGE. Mutation of LHX, SOX and octamers, within hs623, caused a reduction of hs623
      activity in MGE primary cultures. CONCLUSIONS: Tcf12 expression in the SVZ of the
      MGE is mediated through aRE hs623. The activity of hs623 is dependent on LHX6,
      SOX and octamers. Thus, maintaining the expression of Tcf12 in the SVZ involves
      on TF pathways parallel and genetically downstream of NKX2-1.

PMID- 30217228
TI  - Research on the mechanism of drug-drug interaction between salvianolate injection
      and aspirin based on the metabolic enzyme and PK-PD model: study protocol for a
      PK-PD trial.
AB  - BACKGROUND: Coronary heart disease (CHD) is a common cardiovascular disease
      accounting for 10-20% mortality by heart disease worldwide. The gold standard
      treatment to manage CHD is aspirin, which may prevent myocardial infarction and
      sudden death; however, long-term use of aspirin may increase its side effects.
      Currently, more and more clinicians are exploring different approaches to use the
      right combination of medicine to enhance the efficacy and reduce side effects.
      Salvianolate can significantly inhibit the aggregation and activation of
      platelets in patients with CHD; however, its optimum combination with western
      medicine is not established or supported by clinical trial results.
      METHODS/DESIGN: This trial is a prospectively planned, open-labeled, parallel
      grouped, single-centered clinical trial with aggregated pharmacodynamics
      pharmacokinetics (PK-PD) data. All treatment courses will last for 10 days and
      blood sample will be acquired before administration on days 8, 9, and 10, and
      after administration at 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 8 h, 12 h,
      and 24 h on day 10. This trial uses PK-PD modeling to provide a description of
      the concentration-effect relationship and an estimate of pharmacological potency
      of the medicine. The primary outcome will be changes in aspirin esterase and
      catechol-o-methyltransferase (COMT) activity at different blood concentrations to
      determine the PK-PD characteristics of the combination of salvianolate and
      aspirin, followed by analysis of the correlation between exposure level and
      pharmacodynamic index of the medicines. DISCUSSION: This trial will aim to
      evaluate the relationship between changes in the pharmacokinetics and therapeutic
      effect index in the combined use of salvianolate and aspirin. It also discusses
      the possible mechanism of medicine combination in the treatment for CHD and
      provides an experimental basis for a clinically rational medicine combination.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT03306550 . Registered on 9 October
      2017. ClinicalTrials.gov
      https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007D8H&se
      ectaction=Edit&uid=U0003QY8&ts=2&cx=oiuc9g.

PMID- 30217229
TI  - The effects of probiotic and selenium co-supplementation on parameters of mental
      health, hormonal profiles, and biomarkers of inflammation and oxidative stress in
      women with polycystic ovary syndrome.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of the co
      administration of probiotic and selenium on parameters of mental health, hormonal
      profiles, and biomarkers of inflammation and oxidative stress in women with PCOS.
      Data on the effects of selenium and probiotic co-supplementation on mental
      health, hormonal and inflammatory parameters of patients with polycystic ovary
      syndrome (PCOS) are scarce. This investigation was carried out to evaluate the
      effects of selenium and probiotic co-supplementation on mental health, hormonal
      and inflammatory parameters in women with PCOS. METHODS: This randomized, double
      blinded, placebo-controlled clinical trial was conducted on 60 subjects, aged 18
      40 years old. Participants were randomly allocated into two groups to intake 8 *
      109 CFU/day probiotic plus 200 MUg/day selenium supplements (n = 30) or placebo
      (n = 30) for 12 weeks. Hormonal and inflammatory parameters were measured at
      baseline and after the 12-week intervention. RESULTS: Probiotic and selenium co
      supplementation resulted in a significant improvement in beck depression
      inventory (beta - 0.76; 95% CI, - 1.26, - 0.26; P = 0.003), general health
      questionnaire scores (beta - 1.15; 95% CI, - 1.97, - 0.32; P = 0.007) and
      depression anxiety and stress scale scores (beta - 1.49; 95% CI, - 2.59, - 0.39;
      P = 0.009) compared with the placebo. Furthermore, probiotic and selenium co
      supplementation significantly reduced total testosterone (beta - 0.26 ng/mL; 95%
      CI, - 0.51, - 0.02; P = 0.03), hirsutism (beta - 0.43; 95% CI, - 0.74, - 0.11; P
      = 0.008), high-sensitivity C-reactive protein (hs-CRP) (beta - 0.58 mg/L; 95% CI,
      - 0.97, - 0.19; P = 0.004) and malondialdehyde (MDA) levels (beta - 0.29 MUmol/L;
      95% CI, - 0.56, - 0.02; P = 0.03), and significantly increased total antioxidant
      capacity (TAC) (beta + 84.76 mmol/L; 95% CI, + 48.08, + 121.44; P < 0.001) and
      total glutathione (GSH) levels (beta + 26.78 MUmol/L; 95% CI, + 4.33, + 49.23; P
      = 0.02) compared with the placebo. CONCLUSIONS: Overall, the co-administration of
      probiotic and selenium for 12 weeks to women with PCOS had beneficial effects on
      mental health parameters, serum total testosterone, hirsutism, hs-CRP, TAC, GSH
      and MDA levels. This study was prospectively registered in the Iranian website (
      www.irct.ir ) for registration of clinical trials ( http://www.irct.ir :
      IRCT20170513033941N22). TRIAL REGISTRATION: IRCT20170513033941N22 .

PMID- 30217230
TI  - Reduced intrinsic DNA curvature leads to increased mutation rate.
AB  - BACKGROUND: Mutation rates vary across the genome. Many trans factors that
      influence mutation rates have been identified, as have specific sequence motifs
      at the 1-7-bp scale, but cis elements remain poorly characterized. The lack of
      understanding regarding why different sequences have different mutation rates
      hampers our ability to identify positive selection in evolution and to identify
      driver mutations in tumorigenesis. RESULTS: Here, we use a combination of
      synthetic genes and sequences of thousands of isolated yeast colonies to show
      that intrinsic DNA curvature is a major cis determinant of mutation rate.
      Mutation rate negatively correlates with DNA curvature within genes, and a 10%
      decrease in curvature results in a 70% increase in mutation rate. Consistently,
      both yeast and humans accumulate mutations in regions with small curvature. We
      further show that this effect is due to differences in the intrinsic mutation
      rate, likely due to differences in mutagen sensitivity and not due to differences
      in the local activity of DNA repair. CONCLUSIONS: Our study establishes a
      framework for understanding the cis properties of DNA sequence in modulating the
      local mutation rate and identifies a novel causal source of non-uniform mutation
      rates across the genome.

PMID- 30217231
TI  - Safety of on-scene medical care by EMS nurses in non-transported patients: a
      prospective, observational study.
AB  - BACKGROUND: After on-scene examination and /or treatment, emergency medical
      services (EMS) nurses must decide whether the patient requires further assessment
      or treatment, most frequently in a hospital. The primary objective of this study
      was to assess the reliability of the current EMS protocol by determining whether
      the decision not to transport the patient to a care provider was correct or not.
      METHODS: Adults receiving on-scene medical care by an EMS rapid responder or full
      team without transport to the hospital were included in this prospective
      observational study. The primary outcome measure was secondary consultation
      within 24 h after an on-scene EMS evaluation without transport for the same or a
      closely related complaint. The secondary outcome measures were patient
      satisfaction, type of secondarily consulted health care provider, provisional and
      definitive diagnosis, and correctness of the EMS members' decision to provide on
      scene medical care without transport. RESULTS: Of the 1095 participating
      patients, 271 (24.7%) patients requested secondary medical attention for the same
      complaint. This percentage was significantly larger in incidents attended by an
      ambulance team than by a rapid responder (N = 248 (26.5%) vs. N = 23 (14.4%); p <
      0.05). In eleven (1.0%) cases an urgent medical diagnosis requiring admission was
      missed. A total of 873 (79.7%) patients were satisfied with the decision not to
      be transported. In 44 (4.0%) cases the EMS nurse's decision was rated incorrect
      since the patient needed help contradictory to the EMS nurse's recommendation.
      CONCLUSIONS: The data show that EMS nurses can effectively examine patients, but
      a low threshold of referral for consultation should be considered because one in
      four patients requested secondary medical attention for the same complaint(s)
      again. However, due to a low response rate (11.3%) more research is needed to
      further determine the safety of the current EMS protocol. TRIAL REGISTRATION: Not
      applicable.

PMID- 30217232
TI  - A single determination of C-reactive protein does not suffice to declare a
      patient with a diagnosis of axial spondyloarthritis 'CRP-negative'.
AB  - BACKGROUND: To be eligible to receive treatment with an anti-tumour necrosis
      factor (TNF), non-radiographic axial spondyloarthritis (nr-axSpA) patients
      require either elevated levels of C-reactive protein (CRP) (CRP > upper limit of
      normal (ULN)) or magnetic resonance imaging assessment showing inflammation of
      the sacroiliac joints, in addition to meeting criteria for high disease activity.
      Many axSpA patients are classified as 'CRP-negative', or CRP normal, despite
      having levels close to the ULN, and are therefore formally ineligible for
      treatment. The aim of this study was to investigate the likelihood of a CRP test
      indicating elevated levels in axSpA patients that have previously tested CRP
      normal. METHODS: RAPID-axSpA (NCT01087762) enrolled patients who were either
      magnetic resonance imaging positive or had elevated CRP (> ULN: 7.9 mg/L). CRP
      data from the double-blind period for placebo-randomised patients until re
      randomisation to certolizumab pegol (week 16 for ASAS20 non-responders/week 24
      for ASAS20 responders) were analysed. CRP was assessed at screening, baseline,
      and nine time points to week 24. Linear mixed models were used to investigate
      time trends, variability, and correlations of CRP data. RESULTS: Of 106 placebo
      randomised patients with baseline CRP assessments, 26 (25%) tested CRP normal at
      baseline, of whom 13 (50%) had >= 1 test indicating elevated CRP to week 16. Of
      80/106 (75%) patients with elevated baseline CRP, 25 (31%) had >= 1 normal CRP
      test to week 16. Linear mixed models did not reveal changes in mean CRP across
      placebo patients from baseline to week 24. CONCLUSIONS: In axSpA patients with
      CRP < ULN the CRP test should be repeated after >= 4 weeks as there is a
      substantial chance of finding a positive result for elevated CRP at subsequent
      testing, thereby allowing the patient access to treatment. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01087762 . Registered on 16 March 2010.

PMID- 30217234
TI  - Anesthetic-sensitive ion channel modulation is associated with a molar water
      solubility cut-off.
AB  - BACKGROUND: NMDA receptor modulation by hydrocarbons is associated with a molar
      water solubility cut-off. Low-affinity phenolic modulation of GABAA receptors is
      also associated with a cut-off, but at much lower molar solubility values. We
      hypothesized that other anesthetic-sensitive ion channels exhibit distinct cut
      off effects associated with hydrocarbon molar water solubility, and that cut-off
      values are comparatively similar between related receptors than phylogenetically
      distant ones. METHODS: Glycine or GABAA receptors or TREK-1, TRESK, Nav1.2, or
      Nav1.4 channels were expressed separately in frog oocytes. Two electrode voltage
      clamp techniques were used to study current responses in the presence and absence
      of hydrocarbon series from eight functional groups with progressively increasing
      size at saturated aqueous concentrations. Null response (cut-off) was defined by
      current measurements that were statistically indistinguishable between baseline
      and hydrocarbon exposure. RESULTS: Ion channels exhibited cut-off effects
      associated with hydrocarbon molar water solubility in the following order of
      decreasing solubility: Nav1.2 ~ Nav1.4 ? TRESK ~ TREK-1 > GABAA >> glycine.
      Previously measured solubility cut-off values for NMDA receptors were
      intermediate between those for Nav1.4 and TRESK. CONCLUSIONS: Water solubility
      cut-off responses were present for all anesthetic-sensitive ion channels;
      distinct cut-off effects may exist for all cell surface receptors that are
      sensitive to volatile anesthetics. Suggested is the presence of amphipathic
      receptor sites normally occupied by water molecules that have dissociation
      constants inversely related to the cut-off solubility value. Poorly soluble
      hydrocarbons unable to reach concentrations sufficient to out-compete water for
      binding site access fail to modulate the receptor.

PMID- 30217233
TI  - A three arm cluster randomised controlled trial to test the effectiveness and
      cost-effectiveness of the SMART Work & Life intervention for reducing daily
      sitting time in office workers: study protocol.
AB  - BACKGROUND: Office-based workers typically spend 70-85% of working hours, and a
      large proportion of leisure time, sitting. High levels of sitting have been
      linked to poor health. There is a need for fully powered randomised controlled
      trials (RCTs) with long-term follow-up to test the effectiveness of interventions
      to reduce sitting. This paper describes the methodology of a three-arm cluster
      RCT designed to determine the effectiveness and cost-effectiveness of the SMART
      Work & Life intervention, delivered with and without a height-adjustable desk,
      for reducing daily sitting. METHODS/DESIGN: A three-arm cluster RCT of 33
      clusters (660 council workers) will be conducted in three areas in England
      (Leicester; Manchester; Liverpool). Office groups (clusters) will be randomised
      to the SMART Work & Life intervention delivered with (group 1) or without (group
      2) a height-adjustable desk or a control group (group 3). SMART Work & Life
      includes organisational (e.g., management buy-in, provision/support for standing
      meetings), environmental (e.g., relocating waste bins, printers), and
      group/individual (education, action planning, goal setting, addressing barriers,
      coaching, self-monitoring, social support) level behaviour change strategies,
      with strategies driven by workplace champions. Baseline, 3, 12 and 24 month
      measures will be taken. PRIMARY OUTCOME: Objectively measured daily sitting time
      (activPAL3). SECONDARY OUTCOMES: objectively measured sitting, standing,
      stepping, prolonged sitting and moderate-to-vigorous physical activity time and
      number of steps at work and daily; objectively measured sleep (wrist
      accelerometry). Adiposity, blood pressure, fasting glucose, glycated haemoglobin,
      cholesterol (total, HDL, LDL) and triglycerides will be assessed from capillary
      blood samples. Questionnaires will examine dietary intake, fatigue,
      musculoskeletal issues, job performance and satisfaction, work engagement,
      occupational and general fatigue, stress, presenteeism, anxiety and depression
      and sickness absence (organisational records). Quality of life and resources used
      (e.g. GP visits, outpatient attendances) will also be assessed. We will conduct a
      full process evaluation and cost-effectiveness analysis. DISCUSSION: The results
      of this RCT will 1) help to understand how effective an important simple, yet
      relatively expensive environmental change is for reducing sitting, 2) provide
      evidence on changing behaviour across all waking hours, and 3) provide evidence
      for policy guidelines around population and workplace health and well-being.
      TRIAL REGISTRATION: ISRCTN11618007 . Registered on 21 January 2018.

PMID- 30217235
TI  - Acceptability to patients, carers and clinicians of an mHealth platform for the
      management of Parkinson's disease (PD_Manager): study protocol for a pilot
      randomised controlled trial.
AB  - BACKGROUND: Parkinson's disease is a degenerative neurological condition causing
      multiple motor and non-motor symptoms that have a serious adverse effect on
      quality of life. Management is problematic due to the variable and fluctuating
      nature of symptoms, often hourly and daily. The PD_Manager mHealth platform aims
      to provide a continuous feed of data on symptoms to improve clinical
      understanding of the status of any individual patient and inform care planning.
      The objectives of this trial are to (1) assess patient (and family carer)
      perspectives of PD_Manager regarding comfort, acceptability and ease of use; (2)
      assess clinician views about the utility of the data generated by PD_Manager for
      clinical decision making and the acceptability of the system in clinical
      practice. METHODS/DESIGN: This trial is an unblinded, parallel, two-group,
      randomised controlled pilot study. A total of 200 persons with Parkinson's
      disease (Hoehn and Yahr stage 3, experiencing motor fluctuations at least 2 h per
      day), with primary family carers, in three countries (110 Rome, 50 Venice, Italy;
      20 each in Ioannina, Greece and Surrey, England) will be recruited. Following
      informed consent, baseline information will be gathered, including the following:
      age, gender, education, attitudes to technology (patient and carer); time since
      Parkinson's diagnosis, symptom status and comorbidities (patient only).
      Randomisation will assign participants (1:1 in each country), to PD_Manager vs
      control, stratifying by age (1 <= 70 : 1 > 70) and gender (60% M: 40% F). The
      PD_Manager system captures continuous data on motor symptoms, sleep, activity,
      speech quality and emotional state using wearable devices (wristband, insoles)
      and a smartphone (with apps) for storing and transmitting the information.
      Control group participants will be asked to keep a symptom diary covering the
      same elements as PD_Manager records. After a minimum of two weeks, each
      participant will attend a consultation with a specialist doctor for review of the
      data gathered (by either means), and changes to management will be initiated as
      indicated. Patients, carers and clinicians will be asked for feedback on the
      acceptability and utility of the data collection methods. The PD_Manager
      intervention, compared to a symptom diary, will be evaluated in a cost
      consequences framework. DISCUSSION: Information gathered will inform further
      development of the PD_Manager system and a larger effectiveness trial. TRIAL
      REGISTRATION: ISRCTN Registry, ISRCTN17396879 . Registered on 15 March 2017.

PMID- 30217237
TI  - Basidiobolomycosis in Togo: clinico-pathological study of a series of 12 presumed
      cases.
AB  - OBJECTIVE: The purpose of our study was to describe the histological diagnosed of
      the Basidiobolomycosis cases from 1990 to 2017 (28 years) in the only Pathology
      Anatomy Laboratory in Togo. RESULTS: A total of 12 cases of suspected
      Basidiobolomycosis have been identified. The sex ratio (M/F) was 2. The average
      age of the patients was 24.8 +/- 1.6 years. Six patients (6/12) had a
      pathological history: HIV infection (n = 4 cases) and tuberculosis (n = 2 cases).
      The clinical manifestations were localized to pure skin (n = 9 cases), skin and
      mucous digestive (n = 2 cases) and disseminated (n = 1 cases). Direct mycological
      examination and culture in 4 patients was positive in 3 patients. The samples
      examined consisted of 11 cutaneous biopsies measuring 1-3 cm and a biopsy of the
      intestinal mucosa. Histology showed granulomatous inflammation of the
      dermohypodermal site with numerous giant cells associated with eosinophilic
      polynuclear cells, in which there are 5-7 mm non-septate, irregular mycelial
      filaments. Patients were treated with ketoconazole at a dose of 10 mg/kg daily.
      The progression of the patients' condition was favorable after 4 weeks of
      treatment with a regression of the closets size. Patients were completely healed
      after 8 weeks of treatment, without recurrence after 6 months. No deaths have
      been recorded.

PMID- 30217238
TI  - Expert endorsement, a prerequisite to general acceptance, marked a significant
      milestone in the history of water exchange colonoscopy.

PMID- 30217236
TI  - MAGIC: once upon a time in consent management-a FHIR(r) tale.
AB  - BACKGROUND: The use of medical data for research purposes requires an informed
      consent of the patient that is compliant with the EU General Data Protection
      Regulation. In the context of multi-centre research initiatives and a multitude
      of clinical and epidemiological studies scalable and automatable measures for
      digital consent management are required. Modular form, structure, and contents
      render a patient's consent reusable for varying project settings in order to
      effectively manage and minimise organisational and technical efforts. RESULTS:
      Within the DFG-funded project "MAGIC" (Grant Number HO 1937/5-1) the digital
      consent management service tool gICS was enhanced to comply with the
      recommendations published in the TMF data protection guideline for medical
      research. In addition, a structured exchange format for modular consent templates
      considering established standards and formats in the area of digital informed
      consent management was designed. Using the new FHIR standard and the HAPI FHIR
      library, the first version for an exchange format and necessary import-/export
      functionalities were successfully implemented. CONCLUSIONS: The proposed exchange
      format is a "work in progress". It represents a starting point for current
      discussions concerning digital consent management. It also attempts to improve
      interoperability between different approaches within the wider IHE-/HL7-/FHIR
      community. Independent of the exchange format, providing the possibility to
      export, modify and import templates for consents and withdrawals to be reused in
      similar clinical and epidemiological studies is an essential precondition for the
      sustainable operation of digital consent management.

PMID- 30217239
TI  - Borescope examination: Is there value in visual assessment of endoscope channels?

PMID- 30217240
TI  - Upfront endoscopic submucosal dissection for superficial squamous cell carcinoma
      is superior to upfront surgical therapy.

PMID- 30217241
TI  - Chromoendoscopy: adding color to duodenal polyps.

PMID- 30217242
TI  - Removal of duodenal adenomas: the importance of proper technical application and
      operator expertise.

PMID- 30217243
TI  - "I want a new drug...".

PMID- 30217244
TI  - Postcolonoscopy colorectal cancer rates: monitoring and reducing the worst-case
      scenario.

PMID- 30217245
TI  - Age is not just a number: surveillance colonoscopy is low yield in individuals
      younger than 50.

PMID- 30217246
TI  - Reassessing colectomy in young patients with familial adenomatous polyposis.

PMID- 30217247
TI  - Response.

PMID- 30217248
TI  - Negative withdrawal time: simple and efficient.

PMID- 30217249
TI  - Polyp-adjacent biopsies no longer required in inflammatory bowel disease.

PMID- 30217250
TI  - Response.

PMID- 30217251
TI  - Autologous esophageal mucosa transplantation to prevent esophageal stricture
      after endoscopic submucosal dissection: promising, but too early to draw a
      conclusion.

PMID- 30217253
TI  - Foreword.

PMID- 30217252
TI  - Response.

PMID- 30217254
TI  - Systematic reviews, 'systematic reviews' and more: When variation leads to
      confusion.

PMID- 30217255
TI  - Antioxidant property of Taraxacum formosanum Kitam and its antitumor activity in
      non-small-cell lung cancer cells.
AB  - BACKGROUND: Non-small-cell lung cancer (NSCLC) is known to exhibit resistance to
      various therapeutic agents and become progressively incurable. Taraxacum
      formosanum is a medicinal Chinese herb that has been clinically used in Taiwan.
      However, the investigations of the effects of whole plant on lung cancer are
      limited. PURPOSE: This study evaluated the in vitro antioxidant,
      antiproliferative, and antimigration effects of the ethanol extract of T.
      formosanum (ETF). The possible molecular mechanism underlying its antitumor
      effects on cultured human NSCLC cell lines was also elucidated. METHODS: The
      antioxidant effects of the ETF were determined using 1,1-diphenyl-2
      picrylhydrazyl (DPPH) and Trolox equivalent antioxidant capacity (TEAC) assays,
      and its antiproliferative and antimigration effects were determined using trypan
      blue exclusion and wound healing assays, respectively. In addition, changes in
      the mitogen-activated protein kinase (MAPK) signaling pathway were investigated
      using Western blot analyses. Various inhibitors were used to determine the roles
      of the MAPK signaling pathway involved in the molecular mechanism of the ETF.
      RESULTS: Our results showed that the ETF exhibited strong reducing power, a high
      Trolox equivalent antioxidant capacity (TEAC) value, and potent 1,1-diphenyl-2
      picrylhydrazyl (DPPH) free radical scavenging and Fe+2-chelating abilities. The
      ETF also exerted antiproliferative and antimigration effects on NSCLC cells in a
      dose-dependent manner. These effects may be mediated by the inhibitory effects of
      the ETF on the activation of extracellular signal-regulated kinase. CONCLUSIONS:
      This study performed the first pharmacological exploration of T. formosanum. Our
      results demonstrated the antioxidant and antitumor effects of the ETF on NSCLC
      cell lines, indicating their potential preventive and therapeutic values for lung
      cancer.

PMID- 30217256
TI  - Renoprotective effect of Spirulina platensis extract against nicotine-induced
      oxidative stress-mediated inflammation in rats.
AB  - BACKGROUND: Nicotine is an important factor in the pathogenesis of renal injury
      in smokers. PURPOSE: The purpose of the present study was to investigate the
      renoprotective effect of Spirulina platensis extract (SP) against chronic
      nicotine administration in rats. METHODS: Nicotine intoxication was induced with
      0.5 mg/kg BW. Rats received 500 mg SP/kg BW by gastric gavage over 4 weeks.
      RESULTS: Our data revealed that nicotine induced renal dysfunction manifested by
      significant abnormal levels of kidney function markers (creatinine and urea)
      accompanied by increased levels of oxidative stress biomarker (malondialdehyde)
      and inflammatory markers (nitric oxide, Interleukin-6 and tumor necrosis factor
      alpha) while antioxidant status as glutathione level and glutathione S
      transferase activity were found to be decreased significantly as compared with
      controls. It is worthy to note that nicotine toxicity induced significant
      increments in the protein expression levels of nuclear factor kappa B as well as
      caspase-3. Histopathological observations showed tubular necrosis and congestion
      in the endothelial lining glomerular tuft and epithelial lining renal tubules
      with nicotine intoxication. Interestingly, our data demonstrated that SP
      supplementation significantly improved the nicotine-induced kidney dysfunction,
      alleviated the induced-lipid peroxidation, inflammatory, apoptotic protein
      markers, and boosted the enzymatic/non-enzymatic antioxidants. Moreover, it
      attenuated the nicotine-induced histopathological alterations of the kidney
      architecture. CONCLUSION: Thus, it is tempting to recommend dietary approaches
      with Spirulina platensis extract for smokers to minimize the deleterious effect
      of chronic nicotine consumption and smoke exposure-related problems towards
      kidney injury via the antioxidant, anti-inflammatory and antiapoptotic properties
      of Spirulina platensis.

PMID- 30217257
TI  - Potent anti-inflammatory effects of honokiol in human fetal membranes and
      myometrium.
AB  - BACKGROUND: Preterm birth is the most prominent complication attributing to poor
      pregnancy and neonatal outcome. Infection is most commonly implicated in preterm
      birth; it initiates a cascade of inflammatory events that leads to the rupture of
      fetal membranes and spontaneous uterine contractions. Anti-inflammatory agents
      may thus be a therapeutic approach to prevent the premature rupture of fetal
      membranes and block contractions. In non-gestational tissues, the polyphenol
      honokiol has been shown to possess potent anti-inflammatory properties. PURPOSE:
      The aim of this study was to investigate the effect of honokiol on pro
      inflammatory mediators in human gestational tissues. METHODS: Fetal membranes,
      myometrium and freshly isolated amnion cells and primary myometrial cells were
      treated with honokiol in the absence or presence of the products
      lipopolysaccharide (LPS) and fibroblast-stimulating lipopeptide-1 (fsl-1), the
      viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) or the pro
      inflammatory cytokines TNF or IL1B. A luciferase assay was used to determine the
      effect of honokiol on nuclear factor kappa B (NF-kappaB) RelA transcriptional
      activity. RESULTS: Honokiol significantly decreased pro-inflammatory cytokine
      (IL1A, IL6) and chemokine (CXCL8, CXCL1, CCL2) mRNA expression and secretion from
      fetal membranes (amnion and choriodecidua) and myometrium stimulated with LPS,
      fsl-1 or poly(I:C). In amnion cells, honokiol also significantly decreased the
      expression and secretion of the extracellular matrix degrading enzyme MMP9.
      Moreover, in myometrium, honokiol significantly suppressed the expression of the
      contraction associated protein PTGFR, the secretion of the uterotonic
      prostaglandins PGE2 and PGF2alpha, and blocked TNF-induced myometrial cell
      contractility. Finally, honokiol significantly suppressed IL1B- and TNF-induced
      NF-kappaB RelA transcriptional activity in primary amnion and myometrial cells.
      CONCLUSIONS: Honokiol reduced the expression of pro-inflammatory and pro-labour
      mediators in human amnion, choriodecidua and myometrium and that this may be
      facilitated through the suppression of NF-kappaB activation. These results
      indicate that the polyphenol honokiol may be a potent therapeutic for the
      prevention of preterm birth.

PMID- 30217258
TI  - Vitis amurensis Rupr: A review of chemistry and pharmacology.
AB  - PURPOSE: Vitis amurensis Rupr. from the family Vitaceae, is a grape species
      native to the Asian continent. It is a highly attractive plant, used widely
      worldwide. It has been used for several hundred years as a traditional Chinese
      herb. The review focuses on the botanical description, traditional uses,
      phytochemistry, and the biological activities of Vitis amurensis Rupr. to
      evaluate its therapeutic potential uses. METHODS: This review summarizes the
      published data concerning the botanical aspects, traditional usage,
      phytochemistry, and pharmacology of Vitis amurensis Rupr., to evaluate its
      therapeutic potential as an important source of natural compounds with effect
      activities that benefit human health. RESULTS: Vitis amurensis Rupr. has been
      used for several hundred years as a traditional Chinese herb to treat stranguria,
      rheumatoid arthritis-associated edema, chronic hepatitis, nephritis, chronic
      arthritis and traumatic hemorrhage. It is a particularly rich source of the
      oligostilbenes, flavonoids, and anthocyanins, phytochemicals that are associated
      with antioxidant, anti-inflammatory, antibacterial and cardioprotective
      activities. Due to the presence of a multitude of bioactives, a wide array of
      pharmacological activities have been ascribed to different parts of this herb and
      individual compounds, which include antioxidant, antimicrobial, anti
      inflammatory, anticancer, anti-aging, anti-melanogenic, anti-allergic and anti
      viral. CONCLUSION: From a health perspective, Vitis amurensis Rupr. presents
      excellent options for treating various diseases due to its bioactive compounds
      (drug candidates) that exhibit important activities or for developing new
      products.

PMID- 30217259
TI  - In vitro inhibitory properties of sesquiterpenes from Chloranthus serratus on
      cell motility via down-regulation of LIMK1 activation in human breast cancer.
AB  - BACKGROUND: LIM kinase 1 plays an important role in tumor cell invasion and
      metastasis by regulating architecture of actin cytoskeleton, and inhibiting
      activity of this kinase may be a promising strategy to prevent cancer cells from
      distant spread. In our previous studies, we found several extracts from the
      medical herbs in genus Chloranthus to exhibit anti-metastatic effects. PURPOSE:
      The aim of this study is to find LIMK1 inhibitors from Chloranthus serratus, a
      medical herb from genus Chloranthus and to evaluate their effects on cell
      motility. METHODS: Three sesquiterpenes, chloranthalactone E (compound 1),
      serralactone A (compound 2, SERA is used in the further testing), and 8beta,
      9alpha-dihydroxylindan-4(5), 7(11)-dien-8alpha, 12-olide (compound 3) were
      isolated from Chloranthus serratus, and the anti-LIMK1 activities of these
      compounds were investigated by kinase-Glo(r) luminescent kinase assay. Then, the
      anti-LIMK1 properties of SERA were verified by kinase-Glo(r) luminescent kinase
      assay and western blot assay. The effects of SERA on F-actin polymerization and
      cell migration were investigated by Phalloidin dying, AP 48 chamber system and
      ORISTM cell migration assay. Furthermore, the inhibitory effects of SERA on LIMK1
      were confirmed by overexpression of LIMK1 and small interfering RNA (siRNA)
      mediated gene silencing. RESULTS: we reported here that among the three
      sesquiterpenes, SERA showed significantly inhibition on LIMK1 activity, and the
      IC50 values on MDA-MB-231 and MDA-MB-468 cells were 3.14 MUM and 4.64 MUM,
      respectively. Furthermore, it was also found that SERA significantly suppressed
      LIMK1 and cofilin1 phosphorylation, F-actin polymerization and also cell
      migration. Data from LIMK1 overexpression and RNA interfering assay confirmed
      that the inhibitory effects of SERA on LIMK1 was antagonized and enhanced by the
      overexpression and knockdown of LIMK1. CONCLUSION: collectively, it was concluded
      that SERA exhibited significant inhibitory effects on breast cancer cells
      migration, and these effects of this sesquiterpene are due to its properties
      reducing the activation of LIM kinase 1.

PMID- 30217260
TI  - Influence of silibinin and beta-beta-dimethylacrylshikonin on chordoma cells.
AB  - BACKGROUND: Chordoma, slow growing bone tumours originating from remnants of the
      notochord, leave affected patients with a median survival of six years. The high
      recurrence rate of chordoma, together with limited treatment options and bad
      overall prognosis, make the development of new treatment options urgently
      necessary. PURPOSE: In this study, the potential of two natural products,
      silibinin and beta-beta-dimethylacrylshikonin (DMAS), was tested on clival (MUG
      CC1 and UM-Chor1) as well as sacral (MUG-Chor1 and U-CH2) chordoma cell lines.
      The treatment was administered both as single- and combined therapy. METHODS: For
      investigation of cell viability, the Cell Titer 96 Aqueous Non-Radioactive Cell
      Proliferation Assay Kit was used. Apoptosis induction was studied by flow
      cytometry, (Annexin V/SYTOX Green, caspase-3) and RT-qPCR. Pathway analyses were
      performed by western blot. RESULTS: Both drugs were found to reduce cell
      viability alone as well as in combination in a dose dependent manner, with DMAS
      being more efficient than silibinin. The mode of cell death was mainly apoptosis
      in DMAS treated samples, while the combination therapy led to apoptosis as well
      as late-apoptosis/necrosis. Silibinin therapy alone, although reducing cell
      viability, did not lead to significant apoptotic effects in the performed assays.
      Focussing on the molecular mechanism of DMAS induced apoptosis, it was found that
      major genes of the mitochondrial apoptosis pathway, like NOXA and PUMA were
      overexpressed. Additionally, western blot experiments showed a decrease of
      ERK/pERK, STAT3/pSTAT3 (Tyr705) and AKT/pAKT expression/activation levels under
      DMAS treatment. CONCLUSION: DMAS is a promising new candidate for chordoma
      therapy, while silibinin or a combination of both is less favourable.

PMID- 30217261
TI  - Honokiol enhances temozolomide-induced apoptotic insults to malignant glioma
      cells via an intrinsic mitochondrion-dependent pathway.
AB  - BACKGROUND: Temozolomide (TMZ) is a first-line chemotherapeutic drug for
      malignant gliomas. Nonetheless, TMZ-induced side effects and drug resistance
      remain challenges. Our previous study showed the suppressive effects of honokiol
      on growth of gliomas. PURPOSE: This study was further aimed to evaluate if
      honokiol could enhance TMZ-induced insults toward malignant glioma cells and its
      possible mechanisms. METHODS: Human U87 MG glioma cells were exposed to TMZ,
      honokiol, and a combination of TMZ and honokiol. Cell survival, apoptosis,
      necrosis, and proliferation were successively assayed. Fluorometric substrate
      assays were conducted to determine activities of caspase-3, -6, -8, and -9.
      Levels of Fas ligand, Bax, and cytochrome c were immunodetected. Translocation of
      Bax to mitochondria were examined using confocal microscopy. Mitochondrial
      function was evaluated by assaying the mitochondrial membrane potential (MMP),
      reactive oxygen species (ROS), and complex I enzyme activity. Caspase-6 activity
      was suppressed using specific peptide inhibitors. The honokiol-induced effects
      were further confirmed using human U373 MG and murine GL261 cells. RESULTS:
      Exposure of human U87 MG glioma cells to honokiol significantly increased TMZ
      induced DNA fragmentation and cell apoptosis. Interestingly, honokiol enhanced
      intrinsic caspase-9 activity without affecting extrinsic Fas ligand levels and
      caspase-8 activity. Sequentially, TMZ-induced changes in Bax translocation, the
      MMP, mitochondrial complex I enzyme activity, intracellular ROS levels, and
      cytochrome c release were enhanced by honokiol. Consequently, honokiol amplified
      TMZ-induced activation of caspases-3 and -6 in human U87 MG cells. Fascinatingly,
      suppressing caspase-6 activity concurrently decreased honokiol-induced DNA
      fragmentation and cell apoptosis. The honokiol-involved improvement in TMZ
      induced intrinsic apoptosis was also confirmed in human U373 MG and murine GL261
      glioma cells. CONCLUSIONS: This study showed that honokiol can enhance TMZ
      induced apoptotic insults to glioma cells via an intrinsic mitochondrion
      dependent mechanism. Our results suggest the therapeutic potential of honokiol to
      attenuate TMZ-induced side effects.

PMID- 30217262
TI  - Coptidis Rhizoma inhibits NLRP3 inflammasome activation and alleviates renal
      damage in early obesity-related glomerulopathy.
AB  - BACKGROUND: Obese subjects have been considered to be in a state of chronic, low
      grade systemic inflammation. Excess fat accumulation and persistent inflammation
      may promote renal dysfunction, to cause chronic kidney disease (CKD) and even end
      stage kidney failure. Coptidis Rhizoma is a classical traditional Chinese herb
      well known for its hypoglycemic and hypolipidemic properties. The mechanism is
      partially associated with its anti-inflammatory effect. However, this effect is
      rarely investigated in obesity and obesity-related glomerulopathy (ORG). PURPOSE:
      The current study was designed to evaluate the effect of Coptidis Rhizoma on ORG.
      It also aimed to determine whether this renal protection effect of Coptidis
      Rhizoma was related to the inhibition of NLRP3 inflammasome in ORG. METHODS:
      Coptidis Rhizoma concentrated granules were prepared and the main components were
      identified by 3D-High Performance Liquid Chromatography (3D-HPLC) assay. The
      animal model of early stage ORG was established in obesity-prone (OP) rats by
      high protein and high fat diet feeding for 12 weeks. The treatment with Coptidis
      Rhizoma at different dosages was administered by intragastric infusion
      simultaneously. Then body weight, kidney weight, plasma lipid profiles, 24 h
      urine protein/albumin content and kidney histology were measured. Inflammatory
      biomarkers were examined both in the rat plasma and renal cortex. The gene
      expressions of NLRP3 inflammasome complex and NF-kappaB in renal tissues were
      also measured. RESULTS: Coptidis Rhizoma alleviated dyslipidemia and reduced the
      renal weight of the rats with ORG. Meanwhile, urinary albumin to creatinine ratio
      and creatinine clearance rate were significantly improved. Coptidis Rhizoma also
      attenuated glomerular hypertrophy, mesangial hyperplasia, and effacement of
      podocyte foot in renal tissues of ORG rats. In addition, Coptidis Rhizoma
      intervention decreased the levels of proinflammatory cytokines (TNF-alpha, IL
      1beta, IL-6, and IL-18) both in plasma and renal tissue. The gene expression of
      NLRP3 inflammasome was down-regulated and NF-kappaB activity was also inhibited
      by Coptidis Rhizoma in renal tissues of ORG rats. CONCLUSION: Coptidis Rhizoma
      can ameliorate early renal damage in ORG rats and the mechanisms appear to be
      related to the inhibition of NLRP3 inflammasome complex.

PMID- 30217263
TI  - Rhein augments ATRA-induced differentiation of acute promyelocytic leukemia
      cells.
AB  - BACKGROUND: Rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid), a natural
      anthraquinone derivative, is a traditional Chinese herb that has been used as a
      medication in many Asian countries. It has been used as a laxative and stomach
      drug for a long time in both China and Korea. It is well-known to have many
      pharmacological activities, such as anti-cancer, anti-bacterial, anti-fungal,
      anti-oxidant, anti-atherogenic, anti-angiogenic, anti-fibrosis, anti
      inflammatory, hepatoprotective, and nephroprotective properties. However, little
      is known about how rhein may affect the differentiation activities in acute
      promyelocytic leukemia (APL) cells. PURPOSE: The present study was designed to
      examine the anti-leukemic effects of rhein against APL cells and to explore the
      underlying mechanism. METHODS: Cell viability was investigated by MTS assay. To
      examine the differentiation activities in APL cells, the cell surface molecules
      (CD11b, CD14, CCR1 and CCR2), phagocytosis, reactive oxygen species (ROS) were
      determined by flow cytometry. Also, induction of caspase-3 activity and reduction
      of mitochondrial membrane potential (MMP) were determined by flow cytometry. RNA
      and protein expressions were determined by qRT-PCR and western blotting,
      respectively. RESULTS: In this study we assessed the role of rhein in treating
      APL. Interestingly, rhein potentiated all-trans retinoic acid (ATRA)-induced
      macrophage differentiation in NB4 cells by inducing changes in morphology,
      expression of the differentiation markers CD11b and CD14, ROS production,
      phagocytic activity, and expression of CCR1 and CCR2. Signaling through CD11b was
      found to be dependent on ERK activation. Additionally, rhein induced APL cell
      death by activating apoptosis and suppressing the mTOR pathway. CONCLUSION:
      Therefore, we suggest that a combination of rhein and ATRA carries strong
      therapeutic potential through the beneficial differentiation of APL cells.
      Moreover, rhein causes cell death via the activation of apoptosis and suppression
      of survival signals in APL cells. In combination with the ability of rhein to
      promote functional macrophage differentiation in APL, these properties suggest
      that a combined treatment of rhein and ATRA has great potential as an anti
      leukemic therapy for APL.

PMID- 30217264
TI  - Inhibitory effect of Ligustrum vulgare leaf extract on the development of
      neuropathic pain in a streptozotocin-induced rat model of diabetes.
AB  - BACKGROUND: Chronic hyperalgesia and allodynia associated with progressive damage
      of peripheral neurons are the most prevalent complications of diabetes mellitus.
      Plants belonging to the family of Oleaceae were traditionally used in folk
      medicine for the management of diabetes. HYPOTHESIS/PURPOSE: The aim of this
      study was to investigate whether an aqueous extract from the leaves of Ligustrum
      vulgare (common privet) could be useful to target neuropathic pain in a rat
      streptozotocin (STZ) model of diabetes. METHODS: The chemical composition of the
      aqueous extract from privet leaf was characterized with the UHPLC-DAD-MS method
      and the analytical quantification of its constituents was performed with HPLC
      DAD. Mechanical hyperalgesia and allodynia were evaluated with the Randall
      Selitto and von Frey tests. RESULTS: Our investigation revealed the presence of
      secoiridoids: oleacein (23.48 +/- 0.87 mg/g), oleocanthal (8.44 +/- 0.08 mg/g),
      oleuropein (1.50 +/- 0.01 mg/g), as well as phenylpropanoids: echinacoside (6.46
      +/- 0.07 mg/g), verbascoside (4.03 +/- 0.04 mg/g) and p-coumaroyl glucarates in
      the dried aqueous extract of privet leaves. Behavioral data indicated that
      chronic intraperitoneal administration of the extract (50-200 mg/kg) for 21 days
      resulted in a decrease in diabetes-induced hyperalgesia and allodynia. Blood
      glucose levels remained unaltered, while body weight and water intake decreased
      significantly. CONCLUSION: The aqueous privet leaf extract could serve useful in
      facilitating treatment of painful diabetic neuropathy. Additionally, the study
      showed that the antihyperalgesic activity of Ligustrum vulgare leaf extract is
      not likely related to its antihyperglycemic properties.

PMID- 30217265
TI  - Metabolic profiling of hypoxia/reoxygenation injury in H9c2 cells reveals the
      accumulation of phytosphingosine and the vital role of Dan-Shen in Xin-Ke-Shu.
AB  - BACKGROUND: Xin-Ke-Shu (XKS), a patent medicine consisting of five commonly used
      traditional Chinese herbs, is used for the treatment of coronary heart diseases.
      A previous study showed that XKS has protective effects for ameliorating
      myocardial ischemia/reperfusion (I/R) injury. PURPOSE: This study was aimed to
      deeply understand the mechanisms and compatible principle of XKS against
      hypoxia/reoxygenation (H/R) injury and the contribution of each single herb to
      the efficacy of XKS. METHODS: An H/R model in H9c2 cardiomyocytes was applied to
      mimic I/R injury observed in vivo. The cell viability, the levels of LDH, MDA,
      SOD, and apoptosis were determined to evaluate the cardioprotection of XKS and
      its subtracted formula (knocked out one herb) in H/R injury. Cell metabolomics,
      combined with western blot analysis, was performed to uncover the inert molecular
      mechanism of XKS against H/R injury. RESULTS: Significant protective effects of
      XKS against oxidative stress and apoptosis induced by H/R injury were found in
      the pharmacodynamic evaluation. Moreover, the metabolic profile deviation of the
      H/R group from the control group was mainly ascribed to thirteen metabolites
      involved in four aberrant pathways, in which sphingolipid metabolism was revealed
      as the most relevant pathway involved in H/R injury (impact > 0.1). Notably, the
      accumulation of phytosphingosine (VIP = 5.84) was considered the most likely
      characteristic in H/R injury, which is well known to promote the opening of the
      mitochondrial permeability transition pore (mPTP) and activate cell apoptosis.
      Furthermore, XKS ameliorated all the abnormalities of the metabolic network in
      response to H/R injury. In agreement with this, a western blot analysis showed
      that XKS markedly regulated the over-expression of CaMK II and cleaved caspase-3.
      However, the subtracted formula showed no significant difference in comparison
      with the XKS group on protecting H/R injury except for QDS (subtracted Dan-Shen
      from XKS). CONCLUSION: The roots of Salvia miltiorrhiza Bge. (Dan-Shen) play an
      important role in the regulation of Ca2+ overloading, oxidative stress and
      apoptosis in H/R injury. Our study enabled information from holistic cell
      metabolomics to be used for mechanism and compatibility rule elucidations of
      TCMs.

PMID- 30217266
TI  - Effects of Marantodes pumilum (Kacip Fatimah) on vaginal pH and expression of
      vacoular ATPase and carbonic anhydrase in the vagina of sex-steroid deficient
      female rats.
AB  - BACKGROUND: In sex-steroid deficiency, increased in the pH of vaginal fluid is
      due to low estrogen levels. HYPOTHESIS: Consumption of Marantodes pumilum leaves
      helps to ameliorate increased in vaginal fluid pH in sex-steroid deficient
      condition. PURPOSE: To investigate changes in vaginal fluid pH and expression of
      proteins that participate in pH changes i.e vacoular (V)-ATPases and carbonic
      anhydrases (CA) in the vagina following M. pumilum leaves consumption. METHODS:
      Ovariectomized adult female rats were treated orally with M. pumilum leaves
      extract (MPE) at 100, 250 and 500 mg/kg.b.w and estradiol at 0.2 ug/kg/b.w for 28
      days. At the end of the treatment, vaginal fluid pH was measured in anesthetised
      rats by using micropH probe. Following sacrificed, levels of V-ATPase and CA
      proteins and mRNAs in the vagina were identified by Western blotting and real
      time PCR, respectively. Protein distribution was visualized by
      immunohistochemistry. RESULTS: Administration of MPE causes the pH of vaginal
      fluid to decrease and expression and distribution of vaginal V-ATPase A & B and
      CA II, III, IX, XII and XIII to increase. CONCLUSIONS: The decrease in vaginal
      fluid pH following MPE treatment suggested that this herb has potential to be
      used to ameliorate vaginal fluid pH changes in sex-steroid deficient condition.

PMID- 30217267
TI  - Editorial overview: Systems neuroscience.

PMID- 30217268
TI  - From Synaptic Metaplasticity to Behavioral Metaplasticity.

PMID- 30217269
TI  - Reactive oxygen species as drivers of autoimmune pathology: an Introduction to
      Special Issue "Oxidative stress and altered redox signalling in autoimmune and
      connective tissue diseases".

PMID- 30217270
TI  - We're all itchy, now what?

PMID- 30217271
TI  - Atopic dermatitis in Indian children: The influence of lower socioeconomic
      status.
AB  - Atopic dermatitis (AD) is a chronic inflammatory condition afflicting children
      and adults. In developing countries like India, the scenario is slightly
      different from its western counterparts, where the disease has been commonly
      described. Despite running a milder course, AD still has a significant negative
      impact on the quality of life. Environmental factors have a great influence on
      pathogenesis. While the diagnosis has remained clinical, variations in minor
      clinical features have been observed worldwide. Many indigenous and herbal agents
      are used for its treatment in India, in addition to conventional therapies.
      Treatment modalities in India emphasize less costly therapies and family
      education. This contribution reviews the epidemiologic issues and therapeutic
      differences in the Indian population with AD, highlighting important nuances in
      the care of the Indian patient.

PMID- 30217272
TI  - Epidemiology of adult atopic dermatitis.
AB  - Atopic dermatitis (AD) is driven by a complex gene-environment interaction. Many
      of the risk factors and genetic underpinning previously observed for pediatric AD
      may not apply to adult atopic dermatitis, suggesting that these may largely be
      different disorders. Whereas AD is classically thought of as a pediatric disease,
      recent studies have shown high rates of disease in adults as well. Risk factors
      for persistence of childhood-onset AD, as well as adult-onset AD, are reviewed.
      Adults with AD are particularly vulnerable to exogenous insults from the outside
      environment, including climate, ultraviolet exposure, pollution, irritants and
      pruritogens, and microbes. Finally, adult AD is associated with a substantial
      health care burden, with increased utilization, direct and indirect costs of
      care, and lost work productivity.

PMID- 30217273
TI  - Assessing the severity of atopic dermatitis in clinical trials and practice.
AB  - There is a tremendous need for accurate and reproducible scoring systems for the
      grading of skin disease to further the development of research and standards of
      care. There are presently greater than 60 measures that have been used to assess
      the severity of atopic dermatitis. These assessments vary considerably with
      respect to content, scale, instructions, validity, and concordance. This
      contribution reviews the available scoring systems of atopic dermatitis signs
      based on their design and merit in specific settings. These scores assess
      lesional intensity and/or extent, symptoms, disease course, and epidermal
      function. Scoring atopic dermatitis, Investigator Global Assessment, and Eczema
      Area and Severity Index are the most commonly used assessments of atopic
      dermatitis signs. Eczema Area and Severity Index has emerged as the preferred
      outcome measure of atopic dermatitis signs for use in clinical trials.
      Unfortunately, Eczema Area and Severity Index can be cumbersome in clinical
      practice. Itch intensity (visual analog or numeric rating scales) and Patient
      Oriented Eczema Measure have emerged as the preferred patient-reported outcome in
      clinical trials. Clinicians' gestalt global assessment of severity, Patient
      Oriented Eczema Measure, and intensity of itch may be feasible for clinical
      practice.

PMID- 30217274
TI  - Patient-reported outcomes and quality of life measures in atopic dermatitis.
AB  - Atopic dermatitis (AD) is a complex and heterogeneous disorder with a profound
      symptom burden and harmful impact on multiple domains of quality of life (QOL).
      Many different patient-reported outcome (PRO) measures exist to assess clinical
      manifestations and QOL impairment in AD, but none comprehensively assess all
      aspects of the disease. This review addresses the PRO and QOL measures currently
      used in AD and their properties, strengths, weaknesses, and feasibility for
      assessing AD in randomized controlled trials and clinical practice. Currently,
      the patient-oriented eczema measure (POEM) has emerged as a preferred PRO for AD
      clinical manifestations, though no single instrument has developed as a preferred
      QOL measure. Validated PRO and QOL measures should be incorporated in all
      clinical trials of AD and in clinical practice where feasible.

PMID- 30217275
TI  - Skin diseases associated with atopic dermatitis.
AB  - Atopic dermatitis is a common chronic pruritic inflammatory skin disorder,
      characterized by an abnormal skin barrier, immune dysfunction, and an altered
      skin microbiome. Atopic dermatitis may be seen in conjunction with a variety of
      other skin disorders due to the complex pathogenesis of atopic dermatitis,
      involving genetic and environmental factors that are associated with immune
      dysfunction, barrier defects, and altered skin microbiomes. Skin disorders
      associated with atopic dermatitis include diseases sharing similar genetic
      origins like ichthyosis vulgaris, infectious diseases such as impetigo, and
      eczema herpeticum, in addition to the cutaneous autoimmune diseases, alopecia
      areata, and vitiligo. Atopic dermatitis is also often linked to such benign
      conditions as pityriasis alba and keratosis pilaris. This review discusses the
      cutaneous comorbidities of atopic dermatitis and their relationship via their
      occurrence in conjunction with atopic dermatitis.

PMID- 30217276
TI  - Bacterial colonization, overgrowth, and superinfection in atopic dermatitis.
AB  - Staphylococcus aureus infection is a major burden for individuals with moderate
      to-severe atopic dermatitis and a known inducer of disease exacerbation. This
      increased susceptibility to staphylococcal infections has been attributed to
      abnormalities in the innate immune system of atopic dermatitis (AD) skin,
      including deficits in barrier proteins and lipids, and a muted response in
      generating antimicrobial peptides, all of which is further impaired by the
      activation of Th2 and Th22 immune pathways, which characterizes AD. Skewing of
      the immune response with a reduced Th1:Th2 ratio and increased adherence of
      bacteria to AD skin are also thought to contribute. Bacterial species diversity
      is reduced with flares, concomitant with increases in S. aureus and sometimes
      clinical infection, which has recently been linked to the finding that commensal
      bacteria produce anti-S. aureus factors that contribute to the endogenous
      response. S. aureus produces several virulence factors affecting the skin barrier
      and immune system, including promoting Th2 cell activation. Best practices for
      the management of staphylococcal infections include systemic antibiotics,
      initiation of antiseptics (particularly dilute bleach baths), and sometimes
      periodic intranasal mupirocin. Newer evidence suggests the possibility that
      treatment of the skin with commensal bacterial species could also reduce S.
      aureus growth and increase diversity.

PMID- 30217277
TI  - Atopic dermatitis guidelines: Diagnosis, systemic therapy, and adjunctive care.
AB  - Atopic dermatitis is an important and chronic skin condition that has recently
      been the subject of enormous volumes of basic science, clinical, and
      epidemiologic research. This field is undergoing rapid expansion, making it
      vitally important to integrate the emerging data with our current body of
      knowledge. In 2014, the American Academy of Dermatology published Guidelines of
      Care for the Management of Atopic Dermatitis, composed of four parts, reflecting
      the work of 17 experts from North America and the United Kingdom.1-4 It uses a
      patient-oriented system, SORT (Strength of Recommendation Taxonomy), to provide
      evidence-based guidance in the management of this common, vexing dermatitis.
      These guidelines join a series of similar efforts published recently across the
      world, reflecting universal interest in distilling the tremendous volume of basic
      scientific and clinical data previously generated.5-7 With new therapies rapidly
      emerging, clinicians require a current understanding of the field to be able to
      incorporate new treatments in their practice.

PMID- 30217278
TI  - Oral supplements in atopic dermatitis.
AB  - Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder. The
      disease is typified by chronic pruritus, a series of signs and symptoms
      associated with immune dysfunction (eg, increased immunoglobulin E mediated
      allergies), and abnormal skin barrier dysfunction (eg, increased response to
      irritants). Due to the chronic itch and reactivity, patients and parents of
      affected children will seek therapy. Therapies range from emollients to topical
      medicaments, including topical corticosteroids, and immunosuppressive agents. Due
      to concerns about the side effects of the available agents, patients and their
      loved ones will often seek "natural" agents as therapy. Oral agents that have
      been tried in (AD) include probiotics, vitamins, oils, and such traditional
      therapeutics as Chinese herbals and Ayurvedic agents. At this time probiotics may
      be promising, but there are inadequate data to determine their efficacy. In
      addition, there are significant concerns for the risks associated with Chinese
      herbals, which may be associated with liver failure and death, and Ayurvedic
      agents, which may be tainted with heavy metals. The safest and most effective
      natural agents are topically applied emollients.

PMID- 30217279
TI  - Developing an eczema action plan.
AB  - As physicians, we spend time learning about diseases and their management. The
      key to successful outcomes is the involvement of patients and their families in
      the care of the conditions for which they seek our assistance. For atopic
      dermatitis (AD), all patients require frequent emollients for xerotic skin and
      care of the inflammation, which comes and goes frequently. The levels of care
      required vary by time and patient. Younger patients require the help of parents
      or other family members. A keen understanding of the timing and appropriate use
      of the various treatment modalities is required and is often confusing. Action
      plans, as used in the care of asthma, for instance, can be effectively integrated
      into the overall care instructions for AD and have been indispensable for many of
      my patients and their families. They are one concrete method for patient/family
      engagement in the overall care planning. The action plans can certainly be
      translated into languages appropriate for any practice environment. The following
      brief summary should be of use to those professionals considering the use of this
      technique.

PMID- 30217280
TI  - Experiences with the first eczema school in the United States.
AB  - Patient education programs are beneficial in the treatment of chronic diseases.
      In Germany, France, and other countries worldwide, educating children,
      adolescents, and adults plus the parents of children with atopic dermatitis (AD)
      leads to better coping with the skin disease, as well as to a reduction in the
      severity of the skin symptoms and signs. The results in Europe led to the idea to
      also establish an eczema school in the United States. In the style of the German
      eczema school, an eczema school was founded in 2014 at Temple University,
      Philadelphia, PA. Since then, a team consisting of a dermatologist, psychologist,
      nutritionist, and nurse practitioner has offered an eczema school to interested
      patients with AD and their families three times a year. This patient education
      program consists of three weekly 2-hour sessions, which address proper skin care,
      the itch-scratch cycle, healthy nutrition, and the role of stress in AD. The
      current review summarizes the first experiences with the education program in the
      United States.

PMID- 30217281
TI  - Current concepts in the prevention of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition with a
      profound social, economic, and psychologic impact. An effective prevention
      strategy would have significant socioeconomic implications worldwide. The aim of
      this review is to evaluate the current evidence for prevention strategies,
      including early intervention neonatal emollient therapy, antihistamine use, and
      probiotic supplementation. Although studies were fairly heterogeneous in their
      designs, the current cumulative data support early daily emollient therapy to
      reduce the incidence of AD in at-risk infants. The evidence for antihistamine use
      is limited, and further investigation is necessary to assess its potential role
      in AD prevention. Although several studies reveal a significant reduction in AD
      incidence with prenatal and/or postnatal probiotic supplementation, they differ
      in the strains, timing, dose, treatment duration, and measurement of clinical
      outcomes. Consequently, there are currently no firm guidelines or recommendations
      in place for probiotic use in pregnancy or infancy to prevent AD. Ultimately,
      atopic prevention remains a work in progress, and further investigations are
      needed to better understand the pathogenesis of AD and determine the most
      effective prevention strategies.

PMID- 30217282
TI  - Synergistic effect of platelet-rich plasma injections and scalp lifting in
      androgenetic alopecia.
AB  - Androgenetic alopecia (AGA) is a common hair loss disorder, especially in men and
      the elderly. In this study, we analyzed the therapeutic effects of platelet-rich
      plasma (PRP) injections and embedded sutures in patients with AGA. In each
      participant, we administered different treatments in one area of hair loss that
      was divided into four sections. Each section received one of the following
      treatments: No treatment, PRP injection, suture embedding, and combined PRP
      injection/suture-embedded areas. The thickness of the scalp, and scalp perfusion
      were measured using an ultrasound imaging system and Moor FLPI full-field laser
      perfusion imaging system, respectively. The diameters of the hair were measured
      using optical microscopy. Our results show that PRP injection treatments
      increased the diameter of the hair (P = 0.034), and the combined PRP
      injection/suture-embedded treatments had a significant effect on the thickness of
      the scalp (P = 0.002), the blood flow (P = 0.014) through the scalp, and the
      diameter of the hair (P= 0.013). This study has demonstrated that there is a
      synergistic effect between PRP injections and suture embedding for increasing the
      thickness and blood flow of the scalp, and diameter of the hair. Combined PRP
      injection/suture-embedded PRP injections might have therapeutic benefit for
      patients with AGA.

PMID- 30217283
TI  - Damien de Veuster (1840-1889): A life devoted to lepers.
AB  - Father Damien de Veuster, or Saint Damien of Molokai (1840-1889), was one of the
      pioneers of the holistic approach to care provision for leprosy patients and
      contributed to the overcoming of the patients' social stigmatization. He devoted
      his life to the lepers living in America's only leper colony, on the Hawaiian
      island of Molokai, where people with leprosy were required to live under
      government-sanctioned medical quarantine. Father Damien gained practical skills
      in caring for the sick, eagerly learning wound cleansing, bandaging techniques,
      and drug administration from a nurse. Mahatma Gandhi said that Father Damien's
      work had inspired his own social campaigns in India.

PMID- 30217284
TI  - Performance monitoring method based on balanced partial least square and
      Statistics Pattern Analysis.
AB  - For process monitoring, it's of significance to pay more attention to some
      performance indexes related to quality, economy or security. To this end, a novel
      performance monitoring method based on the prediction of the performance indexes
      is proposed in this paper to promote the efficiency of process monitoring. In
      this study, firstly, the process variables are classified into two categories
      according to the correlation with the performance indexes. Based on the two
      categories of variables, a balanced Partial Least Square algorithm is proposed by
      constructing an enhanced objective function to predict the performance indexes
      which cannot be measured online. Then, the prediction residual is modeled for
      monitoring via the Statistics Pattern Analysis to capture the variation in the
      performance indexes. Finally, two Simulink examples and a practical example are
      utilized for illustration and validation.

PMID- 30217285
TI  - Staging breast cancer by sentinel lymph node biopsy: Do patients with a single
      negative sentinel node (N=1) experience worse outcomes than those with multiple
      negative sentinel nodes (N>1)?
AB  - BACKGROUND: Though sentinel lymph node biopsy (SLNB) is standard of care for
      early breast cancer, concern remains for false negative nodes and potential
      implications for understaging and under-treatment, particularly when only one
      sentinel node is retrieved. We examined whether patients with a single negative
      SLN (N = 1) experience worse survival than those with two or more negative SLNs
      (N > 1). METHODS: This retrospective review examined 730 SLN-negative patients.
      Clinicopathologic and demographic data, recurrence-free and overall survival were
      assessed. Statistical analysis included Chi square tests, Kaplan-Meier survival
      analysis with log-rank tests, and multivariate analysis using the Cox regression
      model. RESULTS: There were no statistically significant differences in recurrence
      free or overall survival between patients in the N = 1 versus the N > 1 group
      (log rank test, p = 0.75 and p = 0.52, respectively). There were also no
      differences in local and distant recurrence (1.9% versus 2.1%, p = 0.89 and 2.4%
      versus 2.3%, p = 0.78) or breast cancer death (2.4% versus 2.7%, p = 0.85).
      Increased tumor size was associated with finding greater than one negative
      sentinel node intraoperatively (p = 0.01). CONCLUSIONS: A single negative
      sentinel node did not portend worse recurrence-free or overall survival. After
      thorough axillary exploration during SLNB, retrieval of a single negative SLN did
      not result in worse clinical outcomes.

PMID- 30217286
TI  - An updated meta-analysis of transanal drainage tube for prevention of anastomotic
      leak in anterior resection for rectal cancer.
AB  - BACKGROUND: Anastomotic leakage (AL) is one of the most serious complications
      after anterior resection for rectal cancer. Transanal drainage tube (TDT)
      placement is widely used to reduce AL, but its efficacy remains controversial. We
      performed a meta-analysis to evaluate the effectiveness of TDT for prevention of
      AL, using updated evidence. METHODS: Randomized controlled trials (RCTs) and
      cohort studies evaluating the effectiveness of TDT for prevention of AL after
      anterior resection for rectal cancer were identified by using a predefined search
      strategy. Meta-analysis was performed to estimate the pooled rates of AL,
      reoperation, anastomotic bleeding and mortality separately. RESULTS: One RCT and
      ten cohort studies which including 1170 cases with TDT and 1262 cases without TDT
      were considered eligible for inclusion. Meta-analysis showed that the TDT group
      was associated with a significant lower rates of AL (RR: 0.42, 95% CI: 0.31-0.58,
      P < 0.00001) and reoperation (RR: 0.29, 95% CI: 0.19-0.45, P < 0.00001). There
      was no significant difference in anastomotic bleeding rate and mortality between
      the two groups. CONCLUSIONS: TDT placement is associated with significant lower
      rates of AL and reoperation, hence it is likely to be an effective method of
      preventing and reducing AL after rectal cancer surgery.

PMID- 30217287
TI  - Ileus and small bowel obstruction after radical cystectomy for bladder cancer:
      Analysis from the Nationwide Inpatient Sample.
AB  - PURPOSE: To investigate prevalence and predictors of postoperative small bowel
      obstruction (SBO) and ileus in a large cohort of bladder cancer (BCa) patients
      treated with radical cystectomy (RC). METHODS: All patients within the Nationwide
      Inpatient Sample who underwent RC for BCa between 2006 and 2012 were identified.
      First, prevalence of SBO and ileus was analyzed. Second, predictors of these
      bowel-related complications were identified using multivariable regression
      analyses. Third, the association between SBO, ileus, and length of stay was
      evaluated using logistic regression models adjusted for clustering. Prolonged
      length of stay was defined as hospital stay above mean stay of the population
      (>10 days). Fourth, the effect of SBO and ileus on mean inpatient cost of
      healthcare was examined. RESULTS: Of overall 41,498 patients, 1071 (2.6%)
      experienced SBO, and 11,155 (26.9%) experienced ileus. Predictors of ileus
      included age, male gender, black race, hospital characteristics, anemia, chronic
      pulmonary disease, drug abuse, hypothyroidism, fluid and electrolyte disorders,
      and neurological disorders (all p < 0.05) Predictors of SBO included male gender,
      Asian/Pacific islander race, hospital characteristics, congestive heart failure,
      fluid and electrolyte disorders, and psychosis (all p < 0.05). . Postoperative
      SBO (odds ratio (OR) 19.587; 95% confidence interval (CI):15.869-24.167) and
      ileus (OR 5.646; 95% CI:5.336-5.974) were associated with prolonged length of
      stay (all p < 0.001).Median cost of hospital stay was $56.315 for patients who
      developed SBO, $32,472 for patients who developed ileus, and $24,600 for patients
      after cystectomy without ileus or SBO. CONCLUSIONS: Significant prevalence of
      bowel-related complications in patients after RC was observed. These
      complications are strongly associated with prolonged length of stay and higher
      healthcare cost. Increasing awareness of SBO and ileus, identification of
      patients at risk prior to surgery, and implementation of protective strategies
      are strongly indicated in cystectomy patients.?.

PMID- 30217288
TI  - Pancreatoduodenectomy for pancreatic head tumors in the elderly - Systematic
      review and meta-analysis.
AB  - The age at which patients are undergoing pancreatoduodenectomy is increasing
      worldwide. The data on the outcome of this surgical procedure in the elderly is
      constantly expanding. This meta-analysis aims to assess the safety of
      pancreatoduodenectomy in elderly population, primarily focusing on morbidity and
      mortality. We searched the Medline, Embase and Cochrane databases to identify
      eligible studies. The most recent search was performed on 10th April 2017.
      Inclusion criteria were: (1) comparison of the characteristics and perioperative
      outcomes of older patients versus younger patients undergoing
      pancreatoduodenectomy; (2) objective evaluation of mortality or overall
      morbidity; and (3), publication in English. Exclusion criteria were: (1) a lack
      of comparative data; (2) a lack of primary outcomes or insufficient data to
      analyze; (3) a focus on procedures other than pancreatoduodenectomy; or (4), the
      impossibility of extraction of data specifically concerning
      pancreatoduodenectomy. Primary outcomes were overall morbidity and mortality.
      Secondary outcomes analyzed postoperative complications, R0 rate and length of
      hospital stay. 45 eligible studies were chosen, with a combined total of 21,295
      patients. Older patients compared to younger patients had a higher risk of death
      (2.26% vs. 4.54%; RR: 2.23; 95% CI 1.74-2.87) and a higher complication rate
      (47.23% vs. 39.35%; RR: 1.17; 95% CI 1.12-1.24). There were no differences in
      pancreatic fistula occurrence (p = 0.27), bile leakage (p = 0.81), postoperative
      hemorrhage (p = 0.08), or R0 rate (p = 0.92). Our review confirms, that in the
      case of pancreatoduodenectomy, advanced age is a risk factor for increased non
      surgical morbidity and, by extension, higher mortality.

PMID- 30217289
TI  - A predictive model for survival of gallbladder adenocarcinoma.
AB  - BACKGROUND: Gallbladder cancer (GBC) is a life-threatening disease with a poor
      prognosis worldwide. Although several risk factors for survival have been
      identified, an ideal model for predicting prognosis has still not been developed
      due to the low incidence of GBC. This study aims to solve this dilemma by
      attempting to develop an efficient survival prediction model for GBC. METHODS:
      This is a retrospective study. From January 2009 to June 2016, 164 patients with
      a confirmed histological diagnosis of gallbladder adenocarcinoma were enrolled in
      this study. The cohort was randomly divided into two cohorts, the development
      cohort (n = 110) and validation cohort (n = 54). On the basis of the risk factors
      identified in the development cohort, a nomogram-based predictive model (P-risk
      Plus), composed of carbohydrate antigen 199 and pathological characteristics, was
      established for prognosis. RESULTS: In this model, the calibration curves for the
      1-, 2-, and 3-year survival probabilities were well-matched with the actual
      survival rates. In addition, the highest C-index and best decision curve analysis
      were able to be obviously determined. Meanwhile, the P-risk Plus model result
      yielded a better fit for survival between the development and validation groups.
      CONCLUSION: Compared with conventional tumor stages, our nomogram-based P-risk
      Plus model for gallbladder adenocarcinoma has a better predictive capacity and
      thereby has a better potential to facilitate decision-making clinically.

PMID- 30217290
TI  - Extraskeletal versus Skeletal Ewing Sarcoma in the adult population:
      Controversies in care.
AB  - BACKGROUND AND OBJECTIVES: A lack of consensus exists on the prognosis of
      extraskeletal Ewing sarcoma (EES) relative to its skeletal (ES) counterpart in
      adults. This study sought to characterize outcome differences between the two
      diagnoses. METHODS: From 2004 to 2014, the NCDB identified 2,660 Ewing Sarcoma
      patients. Cox proportional hazards regression analysis was used to identify risk
      factors for overall survival (OS). RESULTS: EES patients were older, more likely
      to be female, and have smaller tumors. Among patients with ES, 4.0% received no
      treatment, 2.5% received local therapy only (surgery and/or radiation), 16.8%
      received chemotherapy only, while 52.2% received combination therapy (local and
      chemotherapy), and 17.0% recieived triple therapy (surgery, radiation and
      chemotherapy). Among patients with EES, 4.3% recived no treatment, 5.6% received
      local therapy only, 15.6% received chemotherapy only, while 47.0% received
      combination therapy, and 21.6% received triple therapy. No difference in OS was
      observed between the two groups (P = 0.816). Factors independently associated
      with OS for ES included age (HR = 1.26, P = 0.01), Charlson-Deyo Score (CDS) >=2
      (HR = 3.66, P < 0.001), combination therapy (HR = 0.39, P < 0.001) and triple
      therapy (HR = 0.34, P < 0.001). For EES, factors for OS were age (HR = 1.52, P <
      0.001), CDS >=2 (HR = 1.90, P = 0.02), combination therapy (HR = 0.44, P <
      0.001), triple therapy (HR = 0.34, P < 0.001) and PNET histology (HR = 1.33, P =
      0.02). CONCLUSIONS: Demographic, histological, and treatment characteristics
      differ between adult patients diagnosed with ES and ESS. However, survival and
      independent predictors of survival are consistent between the two diagnoses.

PMID- 30217291
TI  - Surgical and oncological outcomes of an improved nerve-sparing radical
      hysterectomy technique: 6 years of experience at two centres.
AB  - OBJECTIVE: An improved nerve-sparing radical hysterectomy (NSRH), which is based
      on the paravesico-vaginal space, has been recently introduced in a phase II,
      prospective clinical trial by our team. This study aims to report the surgical
      and oncological outcomes of this improved NSRH. METHODS: One hundred seventy
      seven consecutive patients were enrolled in our study and underwent the improved
      NSRH. The proportion of successful catheter removal and postvoid residual urine
      volume (PVR) of 50 mL or less at postoperative day 7 or day 4 was used to assess
      surgical outcomes. The local control rate (LCR), disease free survival (DFS), and
      overall survival (OS) were used to assess oncological outcomes. RESULTS:
      Postoperative 30-day complications occurred in 27/177 (15.3%) patients. The rate
      of successful catheter removal and PVR of 50 mL or less were 85.2% (23/27) and
      66.7% (18/27) at postoperative day 7, and 73.3% (110/150) and 35.3% (53/150) at
      postoperative day 4. A total of 13 (7.9%) patients showed recurrence after a
      median follow-up time of 39.2 months (range 3.2-68.1 months). The estimated 2
      year and 5-year DFS rates were 92.2% and 91.1%, respectively. Seven (4.2%)
      patients presented local recurrence, and five (3.0%) patients were dead at the
      end of the follow-up period. The estimated 5-year LCR and OS were 95.1% and
      96.2%, respectively. In univariate analysis, International Federation of
      Gynecology and Obstetrics (FIGO) stage, lymphovascular space invasion (LVSI), and
      lymph node metastasis were found to be the prognostic risk factors of DFS.
      Patients with LVSI were associated with a worse DFS according to the multivariate
      analysis. CONCLUSIONS: The improved NSRH in our study may provide better surgical
      outcomes without compromising the survival in patients with early cervical
      cancer.

PMID- 30217292
TI  - Overall survival is similar between women who seek care at one or more
      institutions after diagnosis of operable breast cancer in the community.
AB  - BACKGROUND: As breast cancer diagnoses increase, so does the number of patients
      who are critically evaluating hospital attributes to determine where to receive
      their treatment. Evidence suggests that complex surgeries have better outcomes in
      high volume academic centers. Whether clinical outcomes of women diagnosed with
      operable breast cancer, who are treated by multiple disciplines including non
      complex surgical approaches, differ for those received all or part of their
      treatment at their community cancer center is unclear. We hypothesize that the
      clinical outcomes do not differ for those who received all or part of their care
      at their community cancer center. Our aim is to analyze data from the National
      Cancer Database (NCDB) to assess the clinical characteristics and outcomes of
      patients who received all their treatment at community cancer center when
      compared with those who had part or all of their care elsewhere. METHODS: A
      cohort of 162,803 women diagnosed at a community cancer center with an operable
      breast cancer (clinical stage I - III) between 2005 and 2014 from the NCDB was
      evaluated. Demographics, cancer-specific characteristics and overall survival
      differences between patients who stay at or leave their home institution for
      breast cancer treatment were compared. RESULTS: Within this cohort, patients
      treated at multiple institutions were younger, traveled further from home for
      their care, and were more likely to have no comorbidities (p < 0.001). Overall
      survival adjusted for demographics and cancer stage and subtype did not differ
      based on treatment at one or multiple institutions. CONCLUSIONS: The decision for
      patients to undergo breast cancer treatment in a different institution after
      being diagnosed in a community center does not appear to impact overall survival.

PMID- 30217293
TI  - microRNAs: Key regulators of chemotherapy response and metastatic potential via
      complex control of target pathways in esophageal adenocarcinoma.
AB  - INTRODUCTION: Incidence of esophageal adenocarcinoma (EAC) increased
      significantly over the last decades. Lack of response to chemotherapy is a major
      problem in the treatment of this disease. This study aims to assess the
      biological relevance of characteristic microRNA profiles of chemotherapy
      resistant EAC cells with regards to response to chemotherapy and biological
      behavior. METHODS: We selected 3 microRNAs from characteristic microRNA profiles
      of resistant EAC (miR-27b-3p, miR-200b-3p, and miR-148a-3p). Expression of
      microRNAs was modified in 6 EAC cell lines. Effects on chemotherapy, adhesion,
      migration, apoptosis and cell cycle were assessed using standard assays. Target
      analyses were performed using Western Blot and Luciferase techniques. RESULTS:
      MiR-27b-3p significantly sensitized cells to 5FU and Cisplatin in 83%
      respectively in 33% of cell lines, miR-148a-3p in 67% respectively 33% of cases.
      MiR-200b-3p increased sensitivity only towards 5FU in 50% of cases. Co
      transfections with miR-27b-3p/miR-148a-3p showed an additive effect on response
      to chemotherapy in 50% of cases. Upregulation of miR-148a-3p reduced protein
      expression levels of DNMT-1, MSK-1, Bcl-2 and Bim, and miR-27b upregulation led
      to downregulation of Sp1 and PPARy proteins implicating a potential negative post
      transcriptional control via the respective microRNAs. Finally, we were able to
      confirm Bcl-2 for the first time as direct target of miR-148a-3p in EAC.
      CONCLUSION: This study demonstrates that specific microRNA profiles of
      chemotherapy resistant EAC in fact determine their response to chemotherapy and
      biological behavior. Our data further show that microRNA-mediated regulation of
      chemotherapy resistance is complex, and several microRNAs seem to "co-operate" at
      various steps within a broad number of pathways what fits very well to our
      recently proposed understanding of microRNA-mediated regulation as function of
      cellular functional complexes. These data highlight the promising potential of
      microRNAs to predict or monitor treatment response to chemotherapy in EAC, and to
      potentially modulate tumor biology in a therapeutic approach.

PMID- 30217294
TI  - Incidence, outcomes and prognostic factors during 25 years of treatment of
      chondrosarcomas.
AB  - BACKGROUND: There are few studies detailing the incidence, patient outcomes and
      prognostic factors for chondrosarcomas (CS). Those that do exist have small
      sample sizes and/or use older datasets. The purpose of this study was to
      determine the incidence, overall survival (OS) and prognostic factors for OS of
      CS patients, as well as investigate the efficacy of curettage. METHODS: We
      analyzed data of 2186 patients diagnosed with chondrosarcomas between '89-'13
      from the Netherlands Cancer Registry. The effect of risk factors on OS was
      assessed with a multivariate Cox regression. Median Follow-up was determined with
      reversed Kaplan-Meier. OS was estimated using Kaplan-Meier method. RESULTS: The
      relative incidence of CS was 2.88 per million citizens between '89-'96, 4.15
      between '96-'04 and 8.78 between '05-'13. Most of the increase in incidence came
      from atypical cartilaginous tumours/grade I chondrosarcoma (ACT/CS I). The 3-, 5-
      and 10-years survival were, respectively, 96%, 93% and 88% for ACT/CS I, 82%, 74%
      and 62% for grade II CS and 38%, 31% and 26% for grade III CS. Prognostics
      factors significantly associated with OS were age, histological grade, year of
      diagnosis, tumour location and size. CONCLUSION: The incidence of CS, and
      especially ACT/CS I, has increased over time, which could be driven by both an
      ageing population and increased diagnostic imaging. With the increased number of
      diagnosed ACT/CS I, the number of preventative curettages of this tumour has also
      increased. Despite the supposed preventative character of this treatment, the
      incidence of high-grade CS did not decrease.

PMID- 30217295
TI  - Surgical treatment of pNET - Experience of a "high-volume" center.
AB  - BACKGROUND: Neuroendocrine tumors of the pancreas (pNETs) are a rare disease.
      Grading according to the Ki67-index is the most validated risk factor.
      Nevertheless, controversies exist concerning other prognostic factors. The aim of
      this study was to evaluate published risk factors. METHODS: Patients with
      pancreatic NETs who underwent surgery at our department from 2000 to 2014 were
      analyzed. The patient and tumor characteristics were evaluated. Kaplan-Meier
      analyses, univariate calculations as well as multivariate analyses were
      performed. RESULTS: In total, 98 patients underwent surgery due to a pNET. The
      final study population consisted of 88 patients. Univariate analysis demonstrated
      that overall survival is influenced by tumor grading, local resection margin and
      presence of distant metastases. However, in the multivariate analysis, only
      grading and the resection margin had prognostic significance. The size of the
      primary tumor directly correlated with the probability of metastases.
      Multivisceral operations had no influence on morbidity or mortality. CONCLUSIONS:
      Resection of pNETs is the only curative treatment and is safe. Since the
      incidence of pNETs is low, treatment should be performed at a high-volume center.

PMID- 30217296
TI  - Radiofrequency-assisted liver resection: Technique and results.
AB  - BACKGROUND: Radiofrequency (RF)-assisted liver resection allows non-anatomical
      liver resection with reduced blood loss and offers the opportunity for a
      combination of resection and ablation. However, there are still concerns with
      regard to postoperative complications related to this technique. In the present
      study, we discuss the technical aspects of RF-assisted liver resections and
      analyse the rate of perioperative complications, focusing on post-hepatectomy
      liver failure (PLF), bile leak and abscess, and mortality. METHODS: Between 2001
      and 2015, 857 consecutive open and laparoscopic elective RF-assisted liver
      resections for benign and malignant liver tumours were reviewed retrospectively
      to assess perioperative outcomes. RESULTS: Median intraoperative blood loss was
      130 mL, with 9.8% of patients requiring blood transfusion. Intra-abdominal
      collections requiring percutaneous drainage developed in 8.7% of all patients,
      while bile leak at resection margin developed in 2.8% of the cases. Major liver
      resection was performed in 34% of patients and the incidence of PLF was 1.5% with
      one directly related mortality (0.1%). CONCLUSION: RF-assisted liver resection
      has evolved into a feasible and safe technique of liver resection with an
      acceptable incidence of perioperative morbidity and a low incidence of PLF and
      related mortality.

PMID- 30217297
TI  - Timing of postoperative chemotherapy in patients undergoing perioperative
      chemotherapy and gastrectomy for gastric cancer.
AB  - BACKGROUND: For patients who qualify for perioperative chemotherapy and
      gastrectomy for gastric cancer, the optimal timing of the postoperative
      chemotherapy (PC) seems equivocal. The aim of this study was to evaluate the
      influence of timing of PC on overall survival (OS) in patients receiving
      perioperative chemotherapy. METHODS: Patients undergoing perioperative
      chemotherapy and gastrectomy with curative intent (2010-2014) were extracted from
      the nationwide population-based Netherlands Cancer Registry. Timing of PC was
      analyzed as a linear and categorical variable (<6 weeks, 6-8 weeks, and >8
      weeks). Risk factors for a late start of PC (>=6 weeks), and the association
      between timing of PC and OS were assessed by multivariable regression analyses.
      RESULTS: Among 1066 patients who underwent perioperative chemotherapy and
      gastrectomy, 463 (43%) patients started PC. PC was administered within 6 weeks in
      208 (45%) patients, within 6-8 weeks in 155 (33%) patients, and after 8 weeks in
      100 (22%) patients. A total of 419 (91%) and 351 (76%) patients finished all
      cycles of preoperative and PC, respectively. A late start of PC was associated
      with a longer hospital stay (+1 hospital day: OR 1.15, 95% CI [1.08-1.23], p <
      0.001). Timing of PC was not associated with OS (6-8 weeks vs. <6 weeks, HR 1.14,
      95% CI [0.79-1.65], p = 0.471; >8 weeks vs. <6 weeks, HR 1.04, 95% CI [0.79
      1.65], p = 0.872). CONCLUSION: Timing of postoperative chemotherapy does not
      influence survival in patients receiving perioperative chemotherapy for gastric
      cancer. The results suggest that the early postoperative period may be safely
      used for recovery and optimizing patients for the start of PC.

PMID- 30217298
TI  - Complex distal pancreatectomy outcomes performed at a single institution.
AB  - OBJECTIVE: Discuss the outcomes of distal pancreatectomy in a high volume
      academic community cancer center. INTRODUCTION: Distal pancreatectomy can be done
      with minimal morbidity and mortality in high volume centers. However, there are
      limited reports of distal pancreatectomy being performed in the community. This
      study sought to define the experience with distal pancreatectomy at a high volume
      community cancer center with a dedicated surgical oncology team. METHODS: A
      retrospective chart review was performed for patients undergoing distal
      pancreatectomy performed over a twelve year period (2005-2017) at an academic
      community cancer center. RESULTS: 157 patients underwent distal pancreatectomy.
      The distribution of open, laparoscopic and robotic resections were 96 (61%), 42
      (27%) and 19 (12%) respectively. Concomitant organ resection other than
      splenectomy was performed in 54 (34%) patients. Spleen sparing resections were
      performed in 6 (4%) patients. 84 (54%) out of the 157 resections had a malignant
      lesion on final pathology. Median length of stay was 6 days with 25 (16%)
      patients readmitted within 30 days. Grade 3 or 4 morbidity rate was 18% (28/157).
      The incidence of clinically significant pancreatic fistula (Grade B/C) was 8%
      (13/157). The reoperative rate was 3% (5/157). Overall 30 day mortality in all
      patients was 0.6% (1/157). CONCLUSION: This is the largest series of distal
      pancreatic resections reported in a community cancer hospital. In a high volume
      academic community cancer center with a dedicated surgical oncology team, distal
      pancreatic resections can be performed with short hospital stays, minimal
      morbidity, and a mortality rate of less than 1%.

PMID- 30217300
TI  - Long-term outcomes of laparoscopic versus open D2 gastrectomy for advanced
      gastric cancer.
AB  - BACKGROUND: Technical safety and short-term surgical outcomes of laparoscopy
      assisted gastrectomy (LAG) for advanced gastric cancer (AGC) have been
      investigated in many clinical trials. However, studies with large sample size and
      sufficient follow-up comparing LAG and open gastrectomy (OG) for AGC have seldom
      been reported. The purpose of this study was to compare the long-term outcomes of
      LAG versus open OG for AGC using a propensity score matching analysis. METHODS:
      We retrospectively evaluated 459 and 856 patients who underwent LG or OG with D2
      lymph node dissection, respectively, for AGC between June 2007 and June 2012. One
      to-one propensity score matching was performed to compensate for heterogeneity
      between groups. We compared long-term outcomes between the two groups after
      propensity score matching. RESULTS: In the propensity score-matched cohort, no
      significant differences were observed in 5-year overall survival (OS) (52.0% vs.
      53.4%; P = 0.805) and disease-free survival (DFS) (46.8% vs. 47.3%; P = 0.963)
      between the LAG group and OG group. Stratified analysis showed that the 5-year OS
      and DFS rates were comparable between the two groups in each tumor stage (P >
      0.05). Multivariate analysis revealed that the operation method was not an
      independent prognostic factor for OS or DFS. Further analysis showed that the
      recurrence pattern was similar between the LAG group the OG group (P > 0.05).
      CONCLUSION: LAG is a feasible surgical procedure for AGC in terms of long-term
      prognosis, although the results should be confirmed by the ongoing randomized
      controlled trials.

PMID- 30217299
TI  - Characterizing sarcoma dominance pattern in uterine carcinosarcoma: Homologous
      versus heterologous element.
AB  - OBJECTIVE: To examine significance of sarcoma dominance (SD) patterns in uterine
      carcinosarcoma (UCS). METHODS: This is a secondary analysis of multicenter
      retrospective study examining women with stages I-IV UCS who underwent primary
      surgery. SD was defined as >50% of sarcoma component in uterine tumor. SD
      patterns were grouped as homologous sarcoma without SD (homo/non-dominance, n =
      351), heterologous sarcoma without SD (hetero/non-dominance, n = 174), homologous
      sarcoma with SD (homo/dominance, n = 175), and heterologous sarcoma with SD
      (hetero/dominance, n = 189), and correlated to tumor characteristics and
      survival. RESULTS: SD patterns were significantly associated with age, body
      habitus, carcinoma type, tumor size, depth of myometrial invasion, and nodal
      metastasis (all, P < 0.05). On univariate analysis, SD was associated with
      decreased progression-free survival (PFS) and cause-specific survival (CSS) in
      homologous cases (both, P < 0.05) but not in heterologous cases. On multivariate
      models, both homologous and heterologous SD patterns remained independent
      prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges:
      homo/dominance 1.35-1.69, and hetero/dominance 1.47-1.64) and CSS (adjusted-HR
      ranges: 1.52-1.84 and 1.66-1.81, respectively) compared to homo/non-dominance
      (all, P < 0.05). Among stage I-III disease, when tumors had SD, adding
      radiotherapy to chemotherapy was significantly associated with improved PFS
      (adjusted-HR: homo/dominance 0.49, and hetero/dominance 0.45) and CSS (0.36 and
      0.31, respectively) compared to chemotherapy alone (all, P < 0.05); contrary,
      this association was not observed with absence of SD (all, P > 0.05). CONCLUSION:
      In UCS, SD impacts survival in homologous but not in heterologous type.
      Regardless of sarcoma types, SD was associated with decreased survival in UCS;
      adding radiotherapy to chemotherapy may be an effective postoperative strategy.

PMID- 30217301
TI  - Lower survival after right-sided versus left-sided colon cancers: Is an extended
      lymphadenectomy the answer?
AB  - INTRODUCTION: Tumour location may affect oncologic outcomes for colon
      adenocarcinoma due to different levels of vascular ligation and nodal harvest,
      but the data are equivocal. The objective of this study is to determine the
      effect of tumor location and lymph node yield on overall survival(OS) in stage I
      III colon adenocarcinoma. METHODS: The 2004-2014 National Cancer Database was
      queried for colectomies for non-metastatic colon adenocarcinoma, excluding
      transverse colon and rectal cancer. Patients were grouped based on left/right
      tumor location. Main outcome measure was 5-year OS. Propensity score matching
      created balanced cohorts. Multilevel survival analysis determined the independent
      effect of tumor location and nodal harvest on OS. RESULTS: There were 504,958
      patients (273,198 right; 231,760 left) in the entire cohort: 26.4% stage-I, 37.3%
      stage-II, and 36.3% stage-III (equal distribution left/right). After 1:1
      matching(n = 297,080), right cancers were associated with worse 5-year overall
      survival for stage-II (66% vs. 70%, p < 0.001) and -III (56% vs. 60%, p < 0.001)
      despite similar nodal harvest and proportion receiving systemic therapy. On
      multivariate analysis, right-sided cancers (HR 1.12, 95%CI 1.06-1.19) had worse
      OS, independent of stage and nodal harvest. Nodal harvest >=22 nodes had the
      highest OS (HR 0.71, 95%CI 0.68-0.75). There was an interaction between right
      sided cancer and >22 lymph node harvest towards increased survival (HR 0.86,
      95%CI 0.80-0.92). CONCLUSIONS: Right-sided cancers are associated with worse
      oncologic outcomes compared to left-sided tumors but a higher lymph node yield
      improves survival. These data provide indirect evidence for a higher lymphatic
      harvest to improve survival.

PMID- 30217302
TI  - Nephrotoxicity and long-term survival investigations for patients with peritoneal
      carcinomatosis using hyperthermic intraperitoneal chemotherapy with cisplatin: A
      retrospective cohort study.
AB  - BACKGROUND & PURPOSE: Cytoreductive surgery (CRS) plus Hyperthermic
      intraperitoneal chemotherapy (HIPEC) is an effective measure for peritoneal
      carcinomatosis. The cisplatin (CP) applied in HIPEC carries a risk of kidney
      injury. This study aims to investigate CP-induced nephrotoxicity post HIPEC and
      to explore its risk factors. METHODS: From January 2012 to July 2013, 99 patients
      undergoing CRS + HIPEC were retrospectively reviewed. Patients were divided into
      CP and Non-CP HIPEC groups. The RIFLE classification was used to assess the
      severity of acute kidney injury (AKI). Renal and hepatic function, concentrations
      of tumor markers, and postoperative outcomes were compared between groups.
      RESULTS: 47 (47.5%) patients were in the CP HIPEC group, with 52 (52.5%) patients
      in the Non-CP HIPEC group. 11 (11.1%) patients developed AKI, with 10 of them
      from the CP HIPEC group. Two patients with CP-contained HIPEC developed acute
      renal failure. Plasma levels of both urea nitrogen and creatinine were
      significantly increased in the CP HIPEC group compared with the Non-CP HIPEC
      group (P < 0.01). However, postoperative pain (scaled score, 4.2 vs. 3.8; P =
      0.279), length of hospital stay (18.1 vs. 20.2 days; P = 0.285), hospital costs
      ($1 3182 vs. $12 640; P = 0.465) and incidence of postoperative complication
      (25.5% vs. 17.3%; P = 0.337) were similar in both groups, with comparable 3-year
      overall survival observed (38.6% vs. 31.8%, P = 0.319). A multivariate analysis
      indicated that use of CP was an independent risk factor for AKI (P = 0.017, 95%
      CI: 1.277-4.155). CONCLUSIONS: Application of CP during HIPEC is associated with
      an increased risk of nephrotoxicity, without promising long-term survival
      benefit.

PMID- 30217303
TI  - Predictors of survival after intramedullary nail fixation of completed or
      impending pathologic femur fractures from metastatic disease.
AB  - BACKGROUND: Surgical decision-making can be challenging when treating patients
      with osseous metastases. Numerous factors, including expected duration of
      survival, must be considered to ensure optimal operative stabilization of the
      affected bone. However, life expectancy of patients with metastatic carcinoma is
      often difficult to estimate. The goal of our study was to assess the associations
      of various clinical and demographic factors with survival time after
      intramedullary nail fixation of impending or completed pathologic femur
      fractures. METHODS: One hundred thirty-eight consecutive patients treated with
      intramedullary nail fixation for impending or completed pathologic femur
      fractures between 2005 and 2017 were included in this study. Factors related to
      patient survival were assessed with Cox multivariate survival analysis. For all
      analyses, p < 0.05 was considered significant. RESULTS: The median overall
      postoperative survival time was 8.4 months. Lower hemoglobin concentration (p =
      0.001), lower albumin concentration (p = 0.002), and having a group 2 primary
      cancer (p = 0.001) were associated with shorter survival on multivariate
      analysis. When considering the subgroup of 88 prophylactically stabilized
      patients, lower hemoglobin concentration (p = 0.005), lower albumin concentration
      (p = 0.015), and having a group 2 primary cancer (p = 0.037) were predictive of
      shorter survival. CONCLUSION: Several factors are associated with shorter
      survival after intramedullary nail fixation of pathologic femur fractures. These
      factors should be considered by orthopedic surgeons when educating patients and
      determining appropriate treatment.

PMID- 30217304
TI  - Safety and efficacy for robot-assisted versus open pancreaticoduodenectomy and
      distal pancreatectomy: A systematic review and meta-analysis.
AB  - BACKGROUND: This meta-analysis was conducted to compare the clinical safety and
      efficacy of robot-assisted pancreaticoduodenectomy (RAPD) or robot-assisted
      distal pancreatectomy (RADP) with open surgery. METHODS: Multiple databases
      (PubMed, Medline, EMBASE and Cochrane Library) were searched to identify studies
      comparing the outcomes of RAPD and open pancreaticoduodenectomy (OPD) or RADP and
      open distal pancreatectomy (ODP) (up to December 31, 2017). Fixed and random
      effects models were applied according to different conditions. RESULTS: Fifteen
      non-randomized controlled trials (11 RAPD vs. OPD and 4 RADP vs. ODP) involving
      3690 patients were included. Robot-assisted surgery had longer operative time
      (RAPD vs. OPD: P = 0.0005; RADP vs. ODP: P < 0.00001) but lesser blood loss than
      open surgery (RAPD vs. OPD: P = 0.0009; RADP vs. ODP: P = 0.0007). RAPD was
      associated with less wound infection, a lower positive margin rate, lower overall
      complications, and faster postoperative off-bed activity. There was no
      significant difference in the lymph node yield, the rate of pancreatic fistula,
      delayed gastric emptying, reoperation, length of hospital stay and mortality
      between the two groups. Compared with ODP, RADP was associated with less blood
      transfusion, fewer lymph nodes harvested, lower complications and shorter
      hospital stay. There was no significant difference between the two groups in the
      rate of spleen preservation, positive margin, pancreatic fistula, and mortality.
      CONCLUSIONS: Robot-assisted surgery is a safe and feasible alternative to OPD and
      ODP with regard to perioperative outcomes. However, due to the lack of high
      quality randomized controlled trials, the evidence is still limited.

PMID- 30217305
TI  - Inhibition of TNFalpha in peritoneal fluids of patients following colorectal
      resection attenuates the postoperative stress-related increase in colon cancer
      cell migration: A prospective, in vitro study.
AB  - BACKGROUND AND OBJECTIVES: Surgical trauma in patients undergoing colorectal
      cancer resection generates local and systemic inflammatory responses that can
      affect oncological outcomes. Post-operative peritoneal fluids of patients
      undergoing colorectal surgery increase the pro-malignant effect of cancer cells
      in vitro with correlation to elevated TNFalpha in these fluids. This study
      evaluated whether inhibiting TNFalpha in patients' postoperative fluid biopsies
      would attenuate this effect. METHODS: Peritoneal fluids from 53 patients
      undergoing colorectal surgery were sampled before and daily after surgery via
      intra-abdominal drains. Fluid biopsies were evaluated for their impact on the
      migration capacity of colon cancer cells and for cytokine levels. TNFalpha was
      inhibited using infliximab and cell migration was reevaluated. RESULTS: Colon
      cancer migration capacity was increased in postoperative fluid biopsies from all
      patients (P < 0.005) and was elevated compared to pre-resection levels.
      Infliximab attenuated this effect in >90%, decreasing migration capacity by 30%
      (p < 0.001). CONCLUSIONS: Inhibition of TNFalpha in postoperative peritoneal
      fluids attenuates the increase in cancer cell migration capacity generated
      following colorectal resection. These findings correlate with other studies
      suggesting that attenuation of the post-operative inflammatory response may have
      oncological benefit. Clinical studies are needed to evaluate the effect of peri
      operative TNFalpha inhibition in clinical settings.

PMID- 30217306
TI  - Kras-mutation influences outcomes for palliative primary tumor resection in
      advanced colorectal cancer-a Turkish Oncology Group study.
AB  - PURPOSE: We aimed to investigate the prognostic effect of primary tumor resection
      (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal
      cancer (mCRC). METHODS: We retrospectively collected 341 mCRC cases with
      unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery
      group) and the other patients (n = 131) were followed without PTR (the no-surgery
      group). All the patients were treated with bevacizumab combined chemotherapy
      regimens. RESULTS: The median progression free survival (PFS) of the surgery
      group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than
      that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median
      overall survival (OS) of the surgery group was longer than that of the no-surgery
      group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS
      of the surgery group were 10.4 months and 28.2 months, which were significantly
      longer than that of the no-surgery group in Kras-mutant patients (7.8 months and
      18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of
      PFS and OS between the surgery and the no-surgery groups in Kras-wild type
      patients. CONCLUSION: Palliative PTR may improve the survival outcomes for
      unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant
      patients.

PMID- 30217307
TI  - Predictors of chewing and swallowing disorders after surgery for locally advanced
      oral cancer with free flap reconstruction: A prospective, observational study.
AB  - OBJECTIVE: Surgery for locally advanced oral cancer often requires wide
      resections of multiple subsites of the oral cavity, including the oral tongue,
      floor of the mouth, and lower gingiva, and it causes chewing and swallowing
      disorders. The aim of this prospective, observational study was to determine
      which subsites have a greater impact on chewing and swallowing disorders after
      surgery. METHODS: A prospective, observational study was conducted involving 52
      patients who underwent surgery for locally advanced oral cancer with free flap
      reconstruction. The patients' Functional Oral Intake Scale scores were measured
      before surgery and 1 and 3 months after surgery. Possible predictors of chewing
      and swallowing disorders were subjected to univariate analysis and multivariate
      logistic regression analysis. Age, sex, preoperative body mass index, clinical
      stage, extent of mandibular bone resection, floor of the mouth resection, total
      or subtotal glossectomy, laryngeal suspension, bilateral neck dissection, and
      postoperative radiation therapy were the variables evaluated. RESULTS:
      Multivariate logistic regression analysis showed that both anterior or extensive
      mandibular bone resection and postoperative radiation therapy were independently
      associated with poor oral intake after surgery. CONCLUSIONS: The identified
      predictors will be helpful for better management of patients identified as being
      at high risk of chewing and swallowing disorders.

PMID- 30217308
TI  - Knockdown of CEACAM19 suppresses human gastric cancer through inhibition of
      PI3K/Akt and NF-kappaB.
AB  - Gastric cancer directly affects the quality of human life worldwide. Some
      members, which belong to carcinoembryonic antigen-related cell adhesion molecule
      (CEACAM) subfamily, are deregulated in tumors. Of the subfamily, CEACAM19, a new
      member was the research object. Our study sought to explore the potential role of
      CEACAM19 in gastric cancer. According to the immunohistochemistry (IHC), RT-PCR
      and Western blot, CEACAM19 was over-expressed in gastric cancer tissues and
      cells. Moreover, the Western blot analysis showed that the expression of MMP2 and
      MMP9 was inhibited in CEACAM19 knockdown gastric cancer cells. Meanwhile, in SGC
      7901 and MGC-803 cells, the knockdown of CEACAM19 reduced proliferation,
      migration and invasion. Additionally, the Western blot assay revealed that the
      phosphorylation levels of Akt and p65 were declined by the knockdown of CEACAM19.
      Furthermore, the influence of CEACAM19 knockdown was confirmed by the studies in
      vivo. Collectively, our results revealed that the CEACAM19 knockdown prevented
      the gastric cancer progression likely related to inactivating the PI3K/Akt and NF
      kappaB signaling pathways. Our findings provided insights into a promising
      biomarker of gastric cancer and the potential molecule clues for the prevention
      of gastric cancer.

PMID- 30217309
TI  - Pre-treatment Neutrophil-to-Lymphocyte Ratio as a predictor for occult cervical
      metastasis in early stage (T1-T2 cN0) squamous cell carcinoma of the oral tongue.
AB  - BACKGROUND: Optimum management of clinically negative neck (cN0) remains
      controversial in early stage (T1-T2) squamous cell cancer of the oral tongue
      (OTSCC). The purpose of this study was to investigate the value of pre-treatment
      Neutrophil-to lymphocyte ratio (NLR) in predicting occult cervical metastasis in
      stage I and II OTSCC. METHODS: We carried out a retrospective chart review on 110
      patients suffering from early stage OTSCC who were surgically treated with tumour
      excision and elective neck dissection (END). Our cohort was divided in pN+ and
      pN0 groups basing on histopathological examination after elective neck
      dissection. For each patient pre-treatment NLR was calculated. RESULTS: A
      statistically significant relationship between high levels of pre-treatment NLR
      and probability rate for neck occult metastases (0.000496 p-value) has been
      found. On our model the cut-off value was set for NLR >2.93. Above this level the
      probability to finding metastasis in a clinically negative neck increases
      exponentially. CONCLUSION: These preliminary results offer clinicians an easily
      obtainable tool to stratify patients based on risks of metastatic node in whom
      END could be indicated.

PMID- 30217310
TI  - Evaluation and management of thyroid incidentalomas detected prior to the
      parathyroid surgery.
AB  - BACKGROUND: We investigated the management of thyroid incidentalomas associated
      with cases of parathyroid lesions in order to suggest a practical approach to
      their management from a surgical point of view. METHODS: 639 patients underwent
      radiological and ultrasound investigation of the thyroid area because of
      parathyroid disorders and parathyroidectomy and had at least three years of
      follow-up. All follow-up data for these cases were investigated from the moment
      the lesion was detected and up to the last report. RESULTS: Out of 639 cases,
      incidental or asymptomatic thyroid nodules were found in 179 patients (28%), of
      which, 22 patients were operated (parathyroidectomy + thyroidectomy) and 157
      remained with the nodules. For these patients, the average period of follow-up
      was 7 years 5 mo. Following the results of the follow-up, 52 patients (33%) were
      suggested to have surgery of the thyroid gland and 49 were operated (16 total
      thyroidectomies and 33 hemithyroidectomies). The complications after the second
      surgery included recurrent laryngeal nerve palsy (n = 3), superior laryngeal
      nerve palsy (n = 1), permanent hypocalcaemia (n = 8), and surgical damage to the
      internal jugular vein (n = 1). All complications occurred at the previously
      operated side of the neck. CONCLUSION: While surgery remains the management of
      choice for malignant thyroid incidentalomas, for benign cases, if an asymptomatic
      thyroid nodule was detected inside the thyroid lobe on the side of planned
      parathyroidectomy and if the size of the nodule is ?1.5 cm we suggest combined
      parathyroidectomy + hemithyroidectomy.

PMID- 30217311
TI  - Secondary breast reconstruction after mastectomy using the DIEP flap.
AB  - INTRODUCTION: Breast reconstruction is an important element in the successful
      therapy of breast cancer [1]. Thereby, autologous microvascular breast
      reconstruction has been shown to be a reliable technique. The use of a deep
      inferior epigastric perforator (DIEP) flap or a muscle-sparing (MS) free
      transverse rectus abdominis musculocutaneous (TRAM) flap is recognized in many
      centres as gold standard for reconstructive options [2-4]. Based on our
      experiences with 137 patients over a 5-year period we want to highlight the
      technical aspects of the free microsurgical autologous breast reconstruction
      using a DIEP flap. PATIENTS AND METHODS: Between 01/2013 and 12/2017 we treated
      137 patients (age 32-78 years, mean age 52 years) after mastectomy with
      autologous microsurgical free flap breast reconstruction. A DIEP flap was used
      for breast reconstruction in 33 patients. In 104 cases, we performed a muscle
      sparing TRAM flap. In this video we demonstrate the typical sequence of operative
      steps of a DIEP flap in a 32 year old patient after mastectomy due to an invasive
      ductal breast carcinoma. RESULTS: The rate of total flap loss in our department
      was 2.2% including all patients. In less than 1%, partial flap necrosis could be
      observed. 61% of the patients had undergone previous irradiation. Within the
      small number of flap loss, we could not observe a trend towards a correlation
      between flap loss and previous irradiation. CONCLUSION: Autologous breast
      reconstruction using a DIEP or MS-TRAM flap provides a surgically safe technique
      including a low incidence of flap loss in specialized centres.

PMID- 30217312
TI  - Two-step sentinel lymph node mapping strategy in endometrial cancer staging using
      fluorescent imaging: A novel sentinel lymph node tracer injection procedure.
AB  - OBJECTIVE: The current sentinel lymph node (SLN) tracer injection procedure for
      endometrial cancer commonly uses cervical injection, which can detect SLNs of the
      uterine cervix but not the uterine body. This study describes an SLN tracer
      injection procedure, titled two-step SLN mapping, which can identify SLNs of the
      uterine body and cervix using fluorescent imaging with indocyanine green (ICG)
      and results of SLN biopsy. METHODS: In 50 consecutive patients with endometrial
      cancer, two-step SLN mapping was performed during laparoscopic surgical staging
      with the PINPOINT(r) real-time fluorescence imaging system. The first step was to
      identify SLNs of the uterine body. In total, 4-6 mL of ICG was injected into the
      bilateral uterine cornual areas, and lymphatic channels were traced, followed by
      identification and removal of paraaortic SLNs. The second step was to identify
      SLNs of the uterine cervix by injecting 4 mL of ICG into the cervix. After
      harvesting the mapped pelvic SLNs, complete pelvic and paraaortic lymphadenectomy
      was performed to validate the two-step SLN mapping strategy. RESULTS: Our two
      step SLN mapping strategy produced excellent SLN detection rates: 100% (50/50)
      overall for SLNs; 98.0% (49/50) for pelvic SLNs; 94.0% (47/50) for bilateral
      SLNs; and 86.0% (43/50) for paraaortic SLNs. We detected microscopic metastasis
      in harvested SLNs of 4 patients (8.0%). The sensitivity, specificity, and
      negative predictive value of SLN detection were all 100%. There was no false
      negative case. CONCLUSION: The two-step SLN mapping strategy to identify lymph
      nodes from the uterine fundus and cervix was feasible. This strategy could be
      more accurate in identifying paraaortic lymph node metastasis than the cervical
      injection method.

PMID- 30217313
TI  - Robot-assisted inguinal sentinel lymph node biopsy in primary yolk sac tumor of
      the vulva.
AB  - BACKGROUND: Primary yolk sac tumor (YST) of the vulva is extremely rare and only
      introduced in case reports [1]. For those, routine inguinal lymph node dissection
      (LND) in absence of palpable inguinal lymph node is questionable. To avoid
      complications of inguinal LND, such as lymphedema, inguinal sentinel lymph node
      biopsy (SLNB) can be considered [2,3]. Since recent studies reported feasibility
      of robot-assisted inguinal lymphadenectomy [4], we showed the surgical procedures
      of robot-assisted inguinal SLNB. VIDEO: A 33-year-old woman with vulvar YST was
      referred. Two 2 cm sized masses were founded in right vulvar area, and lymph node
      enlargement was detected in only right external iliac area on imaging studies.
      Thus, we planned robot-assisted surgical treatment including inguinal SLNB using
      the fluorescent dye indocyanine green (ICG) during surgery for the vulvar YST.
      First, we performed intradermal and peri-tumoral injection of 1 ml solution
      including 1.25 mg of ICG at each 2, 5, 7, and 10 o'clock position for the two
      tumors. Fifteen minutes later, three-arm robotic surgical system was installed on
      right thigh. Dissecting the subcutaneous space under the Scarpa's fascia towards
      the inguinal ligament, one fluorescent inguinal sentinel lymph node was
      identified and excised, which showed no tumor on pathologic examination (Fig. 1).
      RESULTS: The procedure time was 70 minutes, and she underwent subsequent robot
      assisted pelvic and para-aortic lymphadenectomy and wide local excision of the
      vulva. CONCLUSION: Robot-assisted inguinal SLNB is feasible. It may be an
      alternative to inguinal LND for avoiding relevant complications in patients with
      vulvar malignancy.

PMID- 30217314
TI  - The rectosigmoid problem.
AB  - The lack of consensus over the transition point for the end of the sigmoid and
      beginning of the rectum is a problem for the colorectal multidisciplinary team.
      In this review, we survey the wide number of landmarks for the rectosigmoid
      junction, and describe the theoretical and evidence-based strengths and
      weaknesses of each one. Without a reliable definition of the rectum, sigmoid and
      rectal cancers will be classified inconsistently. As the treatment strategies for
      sigmoid and rectal cancers are radically different, incorrect tumour localisation
      has a substantial impact on patient management, leading to under or over
      treatment. Inconsistent classification will confound investigation of metastatic
      patterns and treatment outcomes. Now that the rectosigmoid junction has been
      recognised as a distinct segment of colon by the International Classification of
      Diseases, further heterogeneity in management and outcomes could result to the
      detriment of patients and research. We describe a bespoke, anatomical and
      reliable landmark for the rectosigmoid junction; the sigmoid take-off.

PMID- 30217315
TI  - Role of non-coding RNAs in cardiotoxicity of chemotherapy.
AB  - The long-time paradoxical situation of non-coding RNAs (ncRNAs) has been
      terminated for they emerge as executive at full spectrum of gene expression and
      translation. More recently, it has been demonstrated that some ncRNAs apparently
      are associated with chemotherapy, causing cardiotoxicity, which taint long-term
      recovery of patients in growing body of evidence. The current review focused on
      up-to-date knowledge on regulation change and molecular signaling of ncRNAs, at
      mean time evaluate their potentials as diagnostic biomarkers or therapeutic
      targets to monitor and protect cardio function.

PMID- 30217316
TI  - The completely mobilized remnant stomach: A new choice to reconstruct the
      esophagus in lower thoracic esophageal carcinoma with a history of distal
      gastrectomy.
AB  - OBJECTIVE: It is a significant surgical challenge to reconstruct esophagus for
      the patients following distal gastrectomy (DGE). Remnant stomach seems to be a
      better choice compared with colon or jejunal. But many complicated surgical
      methods were performed because of limitation of feeding vessels. We found the
      remnant stomach remained viable when all the feeding vessels were dissected. We
      used the completely mobilized stomach to reconstruct esophagus successfully in 29
      lower thoracic esophageal carcinoma patients with a history of DGE. METHODS: The
      clinical data of 29 patients were retrospectively analyzed from August 2005 to
      March 2017 who accepted esophagoplasty by the completely mobilized remnant
      stomach. All the vessels of the remnant stomach were dissected including short
      gastric, posterior gastric, left gastric and left gastroepiploic vessels. The DGE
      included 2 Billroth I and 27 Billroth II. RESULT: No perioperative death, no
      remnant stomach necrosis occurred. One Leakage was the iatrogenic injury on the
      remnant stomach. The other postoperative complications were the pulmonary
      infection(5) and arrhythmia(4). CONCLUSION: The completely mobilized remnant
      stomach was viable and functional after dissecting all the feeding vessels.
      Application of it was a new and feasible surgical method to perform
      esophagoplasty with the simpler procedure and less complication.

PMID- 30217317
TI  - Severity classification of Tenosynovial Giant Cell Tumours on MR imaging.
AB  - AIM: Current development of novel systemic agents requires identification and
      monitoring of extensive Tenosynovial Giant Cell Tumours (TGCT). This study
      defines TGCT extension on MR imaging to classify severity. METHODS: In part one,
      six MR parameters were defined by field-experts to assess disease extension on MR
      images: type of TGCT, articular involvement, cartilage-covered bone invasion, and
      involvement of muscular/tendinous tissue, ligaments or neurovascular structures.
      Inter- and intra-rater agreement were calculated using 118 TGCT MR scans. In part
      two, the previously defined MR parameters were evaluated in 174 consecutive, not
      previously used, MR-scans. TGCT severity classification was established based on
      highest to lowest Hazard Ratios (HR) on first recurrence. RESULTS: In part one,
      all MR parameters showed good inter- and intra-rater agreement (Kappa>=0.66). In
      part two, cartilage-covered bone invasion and neurovascular involvement were
      rarely appreciated (<13%) and therefore excluded for additional analyses.
      Univariate analyses for recurrent disease yielded positive associations for type
      of TGCT HR12.84(95%CI4.60-35.81), articular involvement HR6.00(95%CI2.14-16.80),
      muscular/tendinous tissue involvement HR3.50(95%CI1.75-7.01) and ligament
      involvement HR4.59(95%CI2.23-9.46). With these, a TGCT severity classification
      was constructed with four distinct severity-stages. Recurrence free survival at 4
      years (log rank p < 0.0001) was 94% in mild localized (n56, 1 recurrence), 88% in
      severe localized (n31, 3 recurrences), 59% in moderate diffuse (n32, 12
      recurrences) and 36% in severe diffuse (n55, 33 recurrences). CONCLUSION: The
      proposed TGCT severity classification informs physicians and patients on disease
      extent and risk for recurrence after surgical treatment. Definition of the most
      severe subgroup attributes to a universal identification of eligible patients for
      systemic therapy or trials for novel agents.

PMID- 30217318
TI  - Neutrophil/lymphocyte ratio is associated with survival in synovial sarcoma.
AB  - BACKGROUND: Synovial sarcoma is a rare malignant soft tissue tumor, more common
      in adolescents and young adults and entails a poor prognosis. Several good
      prognostic factors have been well established such as age less than 25, size less
      than 5 cm and absence of a poorly differentiated component. Inflammation has a
      well-established role in tumor proliferation and survival. The aim of this study
      was to investigate the prognostic significance of the neutrophil/lymphocyte ratio
      (NLR) in a large cohort of synovial sarcoma patients. METHODS: Retrospective
      study of 169 consecutive patients. We analyzed the relation of preoperative NLR
      on disease-free survival (DFS) and overall survival (OS) using Kaplan-Meier
      curves and Cox proportional models. RESULTS: Of the 169 patients included, there
      were 90(53.3%) females and 79(46.7%) males. Median age was 32yo (11-73). Median
      survival was 34.1 and mean disease-free survival was 21.4 months. Mean tumor size
      was 12.5 cm (1.2-77 cm). Applying receiver operating curve analysis, we
      determined a cut-off value of 3.5. In univariate and multivariate analysis,
      increased NLR was significantly associated with poor OS. A <3.5 NLR was an
      independent prognostic factor in all stages (p = 0.002). CONCLUSIONS: NLR >3.5
      was found to be a reliable prognostic factor in this cohort. Given its widespread
      availability, we believe it's use in clinical practice and further clinical
      trials should be considered.

PMID- 30217319
TI  - Analysis of the clinicopathological features and prognostic factors in 734 cases
      of Chinese Hui and Han patients with adenocarcinoma of the esophagogastric
      junction.
AB  - OBJECTIVE: To explore the clinicopathological features and prognostic factors of
      734 cases of Chinese Hui and Han patients with adenocarcinoma of the
      esophagogastric junction (AEG). METHODS: In total, 734 patients were confirmed to
      have AEG by gastroscopy and pathology at the General Hospital of Ningxia Medical
      University between January 2002 and December 2012. Univariate and multivariate
      analyses of demographic, clinicopathological, and prognostic data were performed.
      RESULTS: In total, 734 AEG patients underwent surgical intervention, including
      169 Hui patients and 565 Han patients. The male to female ratio was 9.5:1 in Hui
      patients and 6.4:1 in Han patients, and the average age in both groups was
      approximately 61 years. The Han patients were more likely to have a cigarette
      smoking history and an alcohol consumption history than the Hui patients (58.8%
      vs. 29.4%, p = 0.000; 45.8% vs. 14.6%, p = 0.000). The 5-year survival rate in
      the Hui and Han patients was 54.3% and 39.9%, respectively (p = 0.024). Age (p =
      0.005), sex (p = 0.015), pathologic T stage (p = 0.056), pathologic N stage (p =
      0.000), pathologic M stage (p = 0.001), number of resected lymph nodes (p =
      0.001) and adjuvant chemoradiotherapy (p = 0.002) were significant independent
      prognostic factors. CONCLUSION: The AEG patients were primarily male and elderly
      in both Hui and Han groups with the prognosis of Hui patients better than Han
      patients. Age, sex, pathologic T3-4 stage, pathologic N stage, pathologic M
      stage, number of resected lymph nodes, and adjuvant chemoradiotherapy were
      significant independent factors predictive of the prognosis of AEG in both
      groups.

PMID- 30217320
TI  - Comparative effectiveness of preoperative, postoperative and perioperative
      treatments for resectable gastric cancer: A network meta-analysis of the
      literature from the past 20 years.
AB  - BACKGROUND: Different preoperative, postoperative or perioperative treatment
      strategies, including chemotherapy or chemoradiotherapy, are available for
      patients with gastric cancer, but conventional meta-analyses that assess two
      alternative treatments are unable to compare differences in overall survival.
      Thus, we performed a network meta-analysis to identify the best treatment
      strategy. METHODS: We systematically searched and assessed studies for
      eligibility and extracted data. We then pooled the data and conducted a Bayesian
      network meta-analysis to combine direct comparisons with indirect evidence. The
      node-splitting method was used to assess the inconsistency. Rank probabilities
      were assessed by the probability of treatment rankings. RESULTS: Thirty-three
      eligible randomized controlled trials were included in the network meta-analysis.
      Four treatments that had significantly improved prognoses when compared with
      surgery only were postoperative chemotherapy [HR = 0.80 with 95% CrI: (0.73,
      0.88)], postoperative chemoradiotherapy [HR = 0.73 with 95% CrI: (0.61, 0.87)],
      preoperative chemoradiotherapy [HR = 0.77 with 95% CrI: (0.62, 0.98)] and
      perioperative chemotherapy [HR = 0.69 with 95% CrI: (0.55, 0.84)]. Preoperative
      chemotherapy, however, did not significantly improve survival when compared with
      surgery alone [HR = 0.94 with 95% CrI: (0.71, 1.2)]. There was no statistically
      significant difference between postoperative chemotherapy, postoperative
      chemoradiotherapy, preoperative chemoradiotherapy and perioperative chemotherapy
      in terms of overall survival. Chemoradiotherapy after D2 lymphadenectomy did not
      significantly improve OS when compared with postoperative chemotherapy [HR = 0.95
      with 95% CrI: (0.73, 1.3)]. CONCLUSION: Among patients with operable gastric
      cancer, perioperative chemotherapy had the highest probability of being the best
      treatment. Further clinical resources may be required to assess the efficacy and
      safety of perioperative chemotherapy for patients with gastric cancer.

PMID- 30217321
TI  - Preoperative therapy and long-term survival in gastric cancer: One size does not
      fit all.
AB  - BACKGROUND: The administration of perioperative chemotherapy represents the
      Western standard of care for patients with locally advanced gastric cancer. The
      aim of this study is to determine if the administration of the preoperative
      component of the perioperative regimen is beneficial in the entire population of
      patients with locally advanced gastric cancer. METHODS: Seventy patients
      undergoing preoperative therapy were compared with 347 patients undergoing
      upfront gastrectomy. Survival analyses were conducted with Kaplan-Meier curves
      and Cox regression. Patients undergoing preoperative therapy or undergoing
      upfront gastrectomy were matched 1:1 using the propensity score matching (PSM)
      method, and a survival analysis was conducted on matched patients. A subgroup
      analysis was conducted by tumor location and Lauren histotype. RESULTS: In
      patients undergoing preoperative therapy, factors significantly associated with
      survival were T and N downstaging, type of gastrectomy, resection status and
      Lauren histotype. Preoperative therapy was not significantly associated with
      survival (p = 0,761 before PSM and p = 0,519 after PSM). After PSM, the
      independent variables significantly associated with survival were type of
      gastrectomy, type of lymphadenectomy, R status and postoperative therapy. In the
      subgroup analysis, preoperative therapy demonstrated a selective association with
      the location of the tumor (p = 0,055) and with Lauren intestinal histotype (p =
      0,002). CONCLUSIONS: Preoperative therapy had a non-significant impact on
      survival in the entire population of gastric cancer patients. The advantage of
      preoperative therapy seems to be limited to patients with proximal tumors and an
      intestinal histology. Future studies should better evaluate the diverse response
      of the different phenotypes of gastric cancer to preoperative therapy.

PMID- 30217322
TI  - Effects of preoperative combined aerobic and resistance exercise training in
      cancer patients undergoing tumour resection surgery: A systematic review of
      randomised trials.
AB  - BACKGROUND: Surgical management remains the cornerstone of treatment for many
      cancers, but is associated with a high rate of postoperative complications, which
      are linked to poor preoperative functional capacity. Prehabilitation may have
      beneficial effects on functional capacity and postoperative outcomes. We
      evaluated the effects of prehabilitation combining endurance and resistance
      training (CT) on physical fitness, quality of life (QoL) and postoperative
      outcomes in cancer patients undergoing tumour resection surgery. METHODS: We
      performed a literature search in PubMed, PEDro, EMBASE (via Scopus) and the
      Cochrane library for clinical trials until September 2017. Randomised controlled
      trials investigating the effects of CT in adult cancer patients undergoing
      surgery were included when at least one of the following outcomes was reported:
      physical capacity, muscle strength, QoL, length of stay (LOS), postoperative
      complications and mortality. RESULTS: Ten studies (360 patients) were retrieved
      and included patients with lung, colorectal, bladder and oesophageal cancer. No
      adverse effects of CT were reported. Compared with the control group, CT improved
      physical capacity (3 of 5 studies), muscle strength (2 of 3 studies) and some
      domains of QoL (2 of 4 studies), shortened LOS (1 of 6 studies) and reduced
      postoperative pulmonary complications (2 of 6 studies). CONCLUSIONS: The benefits
      of CT in cancer population are demonstrated. CT may improve physical fitness and
      QoL and decrease LOS and postoperative pulmonary complications. However, our
      conclusions are limited by the heterogeneity of the preoperative CT programs,
      patient characteristics and measurement tools. Future research is required to
      determine the optimal composition of CT.

PMID- 30217323
TI  - Long-term outcomes in elderly patients with resectable large hepatocellular
      carcinoma undergoing hepatectomy.
AB  - BACKGROUND: In contrast to the feasibility of hepatectomy for resectable large
      hepatocellular carcinoma (HCC, >5 cm) in the younger patients, the concerns of
      benefits for the elderly patients remain in practice. This study aimed to
      evaluate the long-term outcomes and safety after hepatectomy in elderly patients
      with resectable large HCC compared with younger patients. METHODS: Between 2003
      and 2014, a total of 2211 HCC patients were reviewed using a prospective database
      and 257 patients with resectable large HCC undergoing hepatectomy were included:
      79 elderly patients with age >=70 years and 178 younger patients with age <70
      years. The last follow-up was assessed in December 2017. The complications, long
      term outcomes and risk factors of disease-free and overall survival were
      analysed. RESULTS: The 1-, 3-, 5- and 7-year overall survival rates in the
      elderly and younger groups were 76%, 55%, 48%, and 42% and 79%, 57%, 51%, and
      49%, respectively (P = 0.319). The 1-, 3-, 5-, and 7-year disease-free survival
      rates in the elderly and younger groups were 60%, 40%, 38%, and 27% and 54%, 36%,
      32%, and 32%, respectively (P = 0.633). The analysis of post-operative outcomes
      of interest, including hospital stay and hospital death and hepatectomy-related
      complications in both groups revealed no significant difference. Serum albumin
      and AJCC TNM stage were independent risk factors for survival. Serum alpha
      fetoprotein, tumour number and AJCC TNM stage predicted HCC recurrence.
      CONCLUSIONS: Our results suggested that hepatectomy can achieve comparable long
      term outcomes in the selected younger and elderly patients with resectable large
      HCC.

PMID- 30217324
TI  - Comparative study of aggression - Dangerousness on patients with paranoid
      schizophrenia: Focus on demographic data, PANSS, drug use and aggressiveness.
AB  - This cross sectional study aimed to compare the differences in psychopathology of
      Greek homicide and homicide attempters, patients with schizophrenia, with non
      violent individuals, suffering from schizophrenia. The study compared three
      Groups of 220 men, diagnosed with schizophrenia: (a) Group Alpha (Schizophrenia -
      No violence, (b) Group Beta (Schizophrenia - with violence or violent crime), (c)
      Group C (Schizophrenia - not guilty by reason of insanity - violent crime).
      Several psychometric tools were used, such as M.I.N.I (Mini-International
      Neuropsychiatric Interview), PANSS scale (Positive and Negative Symptoms Scale).
      Most subjects suffered from paranoid schizophrenia. On factors such as
      demographic characteristics (i.e. current occupational status, living status),
      statistically significant findings were shown for Groups B and C vs Group A.
      Predisposing psychosocial factors, such as family conflicts and aggressiveness
      against family, were found to be statistically significant in differentiating
      violent versus nonviolent individuals with psychosis. They differed significantly
      in factors like history of juvenile delinquency, but also in the type of
      aggressiveness in general. These differences were confirmed on PANSS scale. In
      conclusion, the longer the history of aggressiveness is presented, the greater
      the chances are of individuals falling into Group C and it is possible to spend
      several years from the onset of the disease until the moment of crime.

PMID- 30217325
TI  - Forensic psychiatry in Kuwait - characterization of forensic psychiatry patients
      evaluated over year duration in the only available forensic psychiatry unit.
AB  - INTRODUCTION: The offending behavior arising from a mental disorder invokes
      criminal responsibility doctrines or insanity defenses and calls for legislative
      framework ensuring availability of care and treatment for the patient and
      protection of the public from harm from the offender. The conviction of mentally
      disordered offenders varies depending upon the local legislation and its socio
      cultural context, so do the principles, procedures and guidelines for forensic
      assessments between different countries. The criminal Act of Kuwait, which
      governs the work of forensic psychiatrists remain unchanged, from a psychiatric
      point of view, since it was enacted in the early 1960's. OBJECTIVES: To shed some
      light on the forensic psychiatry services running in Kuwait and describe forensic
      psychiatry patients evaluated in the only-available forensic psychiatry unit.
      METHODS: Retrospective chart review of all cases referred for criminal forensic
      psychiatric assessments during the period from January 1st, 2016 to May 31st,
      2017. The demographics, types of offences, psychiatric diagnoses, and details of
      psychiatric evaluations were retrieved and characterized. RESULTS: A total of 95
      case-notes were reviewed. Most of them were males (90%), Kuwaiti nationals (77%),
      primary or intermediate school education (74%), and were aged 20-39 (69%). Almost
      all (97%) of the referrals required ascertainment of 'responsibility' for the
      alleged offence. Eighty-six percent (N = 81) of the offenders were referred from
      the police or the public prosecutor office. Eighty-three percent (N = 79) of the
      offenders were found to have a mental disorder while 55% (N = 52) were found to
      be criminally responsible. The males (57%) outnumbered the females (33%) as
      criminally responsible. CONCLUSIONS: The number of mentally ill offenders
      referred for criminal responsibility and fitness to stand trial is very small
      compared to western countries. One reason behind this could be that a substantial
      number of the mentally disordered offenders pass undetected through the legal
      system. It is then incumbent that psychiatrists and forensic mental health
      workers might need to provide better awareness and education about mental health
      to legal authorities in Kuwait.

PMID- 30217326
TI  - Systemic limitations in the delivery of mental health care in prisons in England.
AB  - There is a high prevalence of mental health need in prisons, much of which is
      currently unmet. Although considerable research has identified and described this
      mental health need, there has been limited research focussed on reviewing the
      delivery of mental health care in prisons. This study uses content analysis to
      review 36 unannounced prison inspection reports in England to establish whether
      mental health care was provided to an appropriate standard, and whether it is
      equivalent to services that are provided in the wider community. The analysis
      identified four main categories, each of which had further sub-categories:
      managing the process; staffing; range of services; and quality of service.
      Numerous concerns were identified, including: delays to service access; lack of
      appropriate interventions; low staffing levels; limited specialist support; and
      limited access to supervision, training and reflective practice. Despite these
      difficulties, many teams had adopted open referral systems to improve service
      access, had good working relationships and were thought to be providing care of
      good quality. The delivery of mental health care within prisons is still not
      equivalent to that which is provided in the community, and this study has
      identified a number of areas for further improvement.

PMID- 30217327
TI  - Excited delirium syndrome (ExDS): Situational factors and risks to officer safety
      in non-fatal use of force encounters.
AB  - STUDY OBJECTIVE: Police use of force (UoF) encounters include individuals with
      Excited Delirium Syndrome (ExDS) with some frequency. Situational factors and
      risks to officer safety associated with these encounters have not been well
      studied. We examined the likelihood that subjects displaying various concomitant
      features of ExDS were under the influence of drugs and/or alcohol. We also
      examined the extent of subject violence, and the impact of this behaviour on the
      encounter (e.g., the odds of a struggle). Greater understanding of the prevalence
      of ExDS and the specific risk it represents to law enforcement officers and the
      subjects they encounter will guide appropriate policy and response strategies.
      METHODS: A prospective evaluation of a consecutive cohort of subjects involved in
      UoF encounters with police was conducted. Data were collected from January 2012
      to December 2015. Consistent with previous research, the presence of six or more
      features was used to identify probable cases of ExDS. The odds that subjects in a
      state of probable ExDS were under the influence of drugs and/or alcohol was
      calculated and compared against subjects who exhibited less than three features
      of ExDS. In addition, the violent nature of subjects (e.g., the odds of a subject
      being in possession of a weapon) displaying various concomitant features of the
      syndrome was examined. The number of sudden and unexpected arrest-related death
      (ARDs) was documented. RESULTS: UoF occurred in 9006 of 10.9 million police
      public interactions (0.08%). Of the UoF encounters, 156 (1.7%) subjects displayed
      six or more features of ExDS. With four recorded sudden and unexpected ARDs of
      violent and agitated subjects in our cohort, up to 6.3% of these subjects
      experiencing probable ExDS could be expected to be at risk of sudden death.
      Logistic regression analyses indicated that there were significantly higher odds
      that subjects exhibiting more features of ExDS (e.g., six or more) were under the
      influence of drugs. On the other hand, there were significantly lower odds that
      individuals exhibiting ExDS were under the influence of alcohol alone. In
      addition, those displaying a greater number of features demonstrated higher odds
      of engaging in assaultive behaviour, presenting a threat of grievous bodily harm
      or death, and being involved in a struggle that went to the ground with an
      officer. A slight increase in the presence of weapons was observed in encounters
      with probable ExDS. CONCLUSION: Our study provides important information to guide
      the development of policy and procedure in law enforcement. Police encounter a
      subject with ExDS 1 in every 58 UoF incidents (1.7%). Those individuals are at
      higher odds of being intoxicated with drugs according to officers' assessments
      and at risk of being further exerted during a struggle on the ground, both of
      which appear to play a major role in deaths associated to ExDS. There is a
      demonstrable increase in risk to officers and public safety from the violent
      behaviour displayed by subjects presenting a greater number of features of ExDS.
      Our data suggests that up to 6.3% of subjects in a state of ExDS could succumb to
      ARDs; however, we cannot comment on the prevalence of death for persons with ExDS
      who do not encounter police. Further research is needed to determine which force
      options optimize outcome for police and subjects. Additionally, research
      surrounding pathophysiology leading to death should focus on subjects with six or
      more features of ExDS. Ultimately, a better understanding in this area will
      contribute to improving the outcomes of these encounters for those suffering from
      ExDS and those tasked with assisting them.

PMID- 30217328
TI  - Prevention of medical errors and malpractice: Is creating resilience in
      physicians part of the answer?
AB  - In this article, we present key concepts regarding physician and resident
      resilience and burnout, the legal and educational context for these distinctions,
      and the effects of improved physician resilience through self-care on a reduction
      in medical errors and malpractice. Resilience here indicates the mental processes
      and behaviors that enable an individual to overcome the potential negative
      effects of stressors. In order to explore the multiple factors that contribute to
      physician resilience, the authors approached the topic from a variety of
      perspectives, including the current ways of thinking about medical malpractice in
      the United States, physician resilience and medical errors, and building
      resilience during postgraduate medical education. The authors review steps taken
      and in process to mitigate physician burnout and enhance physician resilience.

PMID- 30217329
TI  - Privacy in Big Data psychiatric and behavioural research: A multiple-case study.
AB  - In Big Data health research, concerns have risen about privacy and data
      protection. While the ethical and legal discussion about these issues is ongoing,
      so is research practice. The aim of this qualitative case study is to gain more
      insight into how these concerns are currently dealt with in practice. For this
      multiple-case study, the YOUth cohort, a longitudinal cohort focusing on
      psychosocial development, and Big Data Psychiatry, a pilot study in Big Data
      analytics on psychiatric health data, were selected. A broad range of relevant
      documents were collected and semi-structured interviews with stakeholders were
      conducted. Data were coded, studied and divided into themes during an iterative
      analytical process. Three themes emerged: abandoning anonymisation, reconfiguring
      participant control, and the search for guidance and expertise. Overall, the
      findings show that it takes considerable effort to take privacy and data
      protection norms into account in a Big Data health research initiative,
      especially when individual participant level data need to be linked or enriched.
      By embracing the complexity of the law in an early phase, setbacks could be
      prevented, the existing flexibility within the law could be utilised, and systems
      or organisations could be designed and constructed to take relevant rules into
      account. Our paper illustrates that a close collaboration of experts with
      different backgrounds within the initiative may be necessary to be able to
      successfully navigate this process.

PMID- 30217330
TI  - Relational caring and contact after treatment. An evaluation study on criminal
      recidivism.
AB  - BACKGROUND: Criminal recidivism within two years after discharge from secure
      Forensic Psychiatric Hospitals (FPHs) is high, that is, over 36% for short-term
      judicial measures. It is assumed that relational care during treatment and
      continued voluntary contact and informal care after discharge, are factors that
      contribute to the reduction of criminal recidivism. OBJECTIVE: To examine whether
      the provision of relational care and continued contact after treatment can be
      effective in reducing criminal recidivism two years after discharge (prevalence
      and time to re-offense) in patients who received treatment according to article
      37 of the Dutch Penal Law (i.e., a hospital order for one year) compared to
      patients with the same order receiving Care As Usual. METHODS: An evaluation
      study of criminal recidivism in adult patients (N = 111) residing in 4 FPHs in
      the Netherlands two years after discharge. The intervention 'relational care'
      group was compared with a historical control group from the same hospital before
      the new approach had been introduced, and a concurrent control group from three
      other FPHs in the Netherlands. RESULTS: In the intervention group 15,6% of the
      participants reoffended within two years following discharge, which was
      significantly lower than recidivism in the historical (46,5%) and concurrent
      (47,8%) control group. The odds-ratio for recidivism in the intervention group
      was 0.245 (95% CI: 0.076-0.797) which was significant at p = .019. CONCLUSIONS:
      Patients who received relational care and subsequently were provided with
      voluntary contact after treatment recidivated later and at a lower rate than
      patients from two control groups receiving CAU. Relational care and the voluntary
      continuation of contact and informal (after)care, which was build up during the
      treatment period, may bridge the difficult period that patients face when they
      have left the forensic psychiatric hospital.

PMID- 30217331
TI  - Non-medical approved clinicians: Results of a first national survey in England
      and Wales.
AB  - The 2007 amendments to the Mental Health Act, 1983 in England and Wales enabled
      non-medics to take on the role of legally 'responsible clinician' for the overall
      care and treatment of service users detained under the Act, where previously this
      was the sole domain of the psychiatrist as Responsible Medical Officer. Following
      state sanction as an 'Approved Clinician', certain psychologists, nurses, social
      workers or occupational therapists may be allocated as a Responsible Clinician
      for specific service users. Between 2007 and 2017 only 56 non-medics had become
      Approved Clinicians. This study reports on a first national survey of 39 non
      medical Approved Clinicians. Descriptive statistics and thematic analysis of free
      text answers are presented here. The survey results show the limited uptake of
      the role, save for in the North Eastern region of England. Non-medical Approved
      Clinicians were motivated by a combination of altruistic intents (namely a belief
      that they could offer more psychologically-informed, recovery-oriented care) and
      desire for professional development in a role fitting their expertise and
      experience. Barriers and facilitators to wider uptake of the role appear to be:
      organisational support, attitudes of psychiatrist colleagues and a potentially
      lengthy and laborious approvals application process. The survey is a starting
      point to further research on the interpretation and implementation of the range
      of statutory roles and responsibilities under English and Welsh mental health
      law.

PMID- 30217332
TI  - Relationship between the use of seclusion and mechanical restraint and the nurse
      bed ratio in psychiatric wards in Japan.
AB  - The relationship between the number of nurses in psychiatric wards and frequency
      of use of seclusion and restraint has been unclear. We aimed to clarify this
      relationship in Japanese general psychiatric wards while controlling for patient
      and ward-level characteristics. We hypothesized that seclusion and mechanical
      restraint are less likely to be used in a ward with more nurses. We used data for
      individual admissions from April 2015 to March 2017 in hospitals participating in
      the Psychiatric Electronic Clinical Observation (PECO) system, which extracted
      data from each hospital's electronic health record system. We analyzed the data
      of 10,013 admissions in 113 wards of 23 hospitals. We examined the relationships
      between the number of nurses per 10 beds in each ward and the use of seclusion
      and mechanical restraint, controlling for the patients' age, sex, diagnosis,
      voluntary versus involuntary admission, prescribed dose of antipsychotics,
      severity of symptoms, and length of stay, in addition to ward-level
      characteristics including ward size, location (urban or rural), and type of ward
      (acute ward or not), using multilevel multivariate logistic regression analyses.
      The fraction of admissions exposed to at least one episode of seclusion or
      mechanical restraint was 36.7% and 14.9%, respectively. The odds ratios of the
      number of nurses per 10 beds for the use of seclusion and mechanical restraint
      were 2.36 and 1.74, respectively, indicating that both seclusion and mechanical
      restraint were actually used more frequently in wards with more nurses. A
      possible explanation is that patients anticipated to need coercive measures are
      more likely to be admitted to wards with many nurses. Increasing the number of
      nurses in a ward may not contribute to reducing the use of seclusion and
      restraint.

PMID- 30217333
TI  - The effect of systems collaboration on the individual outcomes of mental health
      court participants: A multi-site study.

PMID- 30217334
TI  - Novel potential inhibitors of complement system and their roles in complement
      regulation and beyond.
AB  - The complement system resembles a double-edged sword since its activation can
      either benefit or harm the host. Thus, regulation of this system is of utmost
      importance and performed by several circulating and membrane-bound complement
      inhibitors. The pool of well-established regulators has recently been enriched
      with proteins that either share structural homology to known complement
      inhibitors such as Sushi domain-containing (SUSD) protein family and Human CUB
      and Sushi multiple domains (CSMD) families or extracellular matrix (ECM)
      macromolecules that interact with and modulate complement activity. In this
      review, we summarize the current knowledge about newly discovered complement
      inhibitors and discuss their implications in complement regulation, as well as in
      processes beyond complement regulation such cancer development. Understanding the
      behavior of these proteins will introduce new mechanisms of complement regulation
      and may provide new avenues in the development of novel therapies.

PMID- 30217335
TI  - Antimicrobial stewardship programs and surgery: What is our role?

PMID- 30217336
TI  - [Management of uveal melanomas, guidelines for oncologists].
AB  - Uveal melanomas are the most frequent primary malignant eye tumor. Enucleation
      was historically the gold standard. Since then, several studies showed that
      conservative treatments did not increase the risk of metastasis or survival.
      Choroidal melanomas are both radioresistant and located close to visual
      structures (the optic nerve and macula) of the eye, which may be preserved in
      some settings without compromising tumor control, as this is the first priority.
      Different types of radiation therapy may be used for such tumors: brachytherapy
      and charged particles, including proton beam therapy. If visual prognosis is
      dependent to the local treatment, the vital prognosis is dependent on the
      metastatic risk, with a risk of liver involvement in 20 to 50% of patients,
      depending on tumor size and genomics. Median survival after the discovery of
      liver metastases is about 15 months. The management of these patients is often
      complex. Systemic therapies (chemotherapy, targeted therapies, immunotherapy,
      etc.) yield limited response rates and although local treatments of liver
      metastases are promising, they are only feasible in selected patients. The
      mission of the MELACHONAT national network is to improve the management of
      patients regardless of the stage of the disease. The patient association ANPACO
      is dedicated to help uveal melanoma patients in their health care path and to
      promote knowledge dissemination within the patient community. The aim of this
      review is to focus on the local treatments of uveal melanomas as well as the
      management of their metastatic evolution.

PMID- 30217337
TI  - Prediction of overall survival after re-irradiation with stereotactic body
      radiation therapy for pancreatic cancer with a novel prognostic model (the SCAD
      score).
AB  - PURPOSE: To develop a predictive model for stratification of patients with
      pancreatic cancer who may achieve survival benefits from re-irradiation with
      stereotactic body radiation therapy (SBRT). METHODS: The score was developed
      based on clinical predictors of OS in 31 patients receiving two courses of SBRT
      with Cox proportional hazards model. Results were then validated in another
      cohort with 11 participants to assess the performance of the score. RESULTS: In
      the training cohort, the median BED10 of the first and second SBRT was 59.5 Gy
      (48-85.5 Gy) and 50.2 Gy (43.7-66.9 Gy) in 5-8 fractions, while in the validation
      cohort, the median BED10 of the first and second SBRT was 59.5 Gy (52.5-66.9 Gy)
      and 47.7 Gy (40.6-54.8 Gy) in 5-8 fractions. The interval between the first and
      second SBRT of the training cohort and validation cohort was 10.5 months (6.1
      24.3 months) and 12.8 months (6.5-29.1 months), respectively. Multivariable
      analysis showed that tumor stage (P = 0.005), BED10 (P = 0.006) and CA19-9
      response (P = 0.04) were significantly predictive of overall survival, which
      formed SCAD score (named after the initials of factors). Patients with the score
      < 3 points had a superior OS compared with those with the score >= 3 points in
      the validation cohort (median OS has not been reached vs. 15.9 months, P =
      0.032). CONCLUSIONS: The SCAD score may have the potential to identify
      individuals benefiting from re-SBRT and be a step toward more personalized
      medicine.

PMID- 30217338
TI  - Bone graft seems to improve 1-year outcomes of surgical treatment of peri
      implantitis defects.

PMID- 30217339
TI  - Clinical performance of a bulk-fill flowable composite and a nanofilled composite
      1 year after restoring noncarious cervical lesions is probably similar.

PMID- 30217340
TI  - [Vascular medicine qualification: First instance].

PMID- 30217341
TI  - Evaluation of short food-frequency questionnaires to assess the dietary pattern
      associated with atherosclerotic cardiovascular diseases.
AB  - OBJECTIVES: Cardiovascular diseases are strongly related to dietary habits. Diet
      can be assessed using dedicated questionnaires that can be self-completed by
      subjects but with the risk of errors. AIM: To compare the completion error rate
      of two questionnaires designed to assess dietary pattern linked to cardiovascular
      diseases and to study the correlation between the two questionnaires. MATERIALS
      AND METHODS: Two questionnaires were used to assess dietary patterns of students:
      the 14-item Food-Frequency-Questionnaire (FFQ) that was validated against
      biomarkers, and the Cardiovascular-Dietary-Questionnaire 2 (CDQ2), which is a 19
      item-FFQ derived from the previous 14-item FFQ. Both questionnaires assessed the
      intake of various food groups associated with either favourable or unfavourable
      effects on cardiovascular risk. A global dietary score was calculated for each
      questionnaire. RESULTS: FFQ and CDQ2 were completed by 150 sport degree students.
      In the case of FFQ, 111 questionnaires out of 150 (74.0%) were incomplete
      compared to only 1 CDQ2 out of 150 (0.7%) (P<0.001). The correlation coefficient
      between the overall CDQ2 score and the FFQ dietary score was 0.53 (P<0.01).
      CONCLUSION: The self-completion of CDQ2 compared to FFQ was associated with far
      less errors. There was a significant correlation between CDQ2 and FFQ. Preference
      should be given to CDQ2 in clinical practice and in studies where dietary pattern
      are evaluated without any interviewer.

PMID- 30217342
TI  - Operated descending thoracic and thoracoabdominal atherosclerotic aortic aneurysm
      prognosis.
AB  - BACKGROUND: The long-term survival of patients treated from descending thoracic
      aneurysm (DTA) is well known, more than those treated from a thoracoabdominal
      aortic aneurysm (TAAA). Moreover, studies are rarely focused on the aneurysmal
      etiology and include both degenerative and post dissecting aneurysms. The aim of
      this study is to compare the long-term survival of patients operated from DTA or
      TAAA due to degenerative atherosclerosis. METHODS: Thirty-nine atherosclerotic
      aneurysm patients were operated between January 2007 and July 2015 at Rouen
      University Hospital. Eighteen DTA patients were operated by TEVAR and 21 TAAA
      patients (8 type I and 13 type III) by open approach. The main endpoint was
      remote survival patients. RESULTS: Overall, the initial population was similar in
      the two groups. However, one third of DTA were treated in context of emergency
      for painful aneurysm versus 9.5% of patients with TAAA (P=0.066). Survival median
      of 18 DTA was 18 months (1-68). Survival median of 21 TAAA followed was 66 months
      (1-91). Survival in both groups was statistically different with the log-rank
      test (P=0.044). CONCLUSIONS: Long-term prognosis of atherosclerotic DTA may be
      worse than that of TAAA's. This retrospective study reflects experience in the
      management of DTA and TAAA in a single-center. Prospective data in patients
      treated with endovascular procedures for DTA or TAAA, with fenesterated or
      branched endoprosthesis, are warranted to confirm these results.

PMID- 30217343
TI  - [Treatment of cancer associated thrombosis: Which role for direct oral
      anticoagulants in 2018?]
AB  - Low molecular weight heparin (LMWH) for at least 3-6 months is the current
      standard of care for the treatment of cancer associated venous thromboembolism
      (VTE). Anticoagulation should be continued as long as the cancer is active. In
      recent years, several direct-acting oral anticoagulants (DOACs) have been
      approved for the treatment of VTE in the general population. These drugs have
      progressively emerged as attractive alternatives with the potential to overcome
      the limitations of LMWH. Due to the lack of high quality prospective data, DOACs
      are currently not recommended for the treatment of cancer associated VTE yet.
      Indeed, evidence supporting the use of DOACs in this specific population remains
      limited, and concerns have been raised about their safety and efficacy in this
      setting. However, a pattern of increased use of DOACs has been observed in the
      cancer population. Meta-analyses of Phase III trials of DOACs in VTE as well as
      analysis of large health care claims databases and non-controlled retrospective
      studies suggest that DOACs might have similar effectiveness and safety to LMWH
      for the management of cancer associated VTE. Results from 2 randomized clinical
      trial (RCT), HOKUSAI-Cancer and SELECT-D, were recently released. Based on a meta
      analysis of these 2 RCTs, compared to LMWH, DOACs had lower 6 month recurrent VTE
      but higher major bleeding. Thus, DOACs should be used with caution in cancer
      patients and a careful evaluation of the risks and benefits for individual
      patients is warranted. Ongoing studies will provide much needed evidence to guide
      clinical care.

PMID- 30217344
TI  - Anticoagulants in frail patients. Seven situations at risk.
AB  - In the case of venous thromboembolic disease (VTE), physicians are facing more
      and more difficulties in managing VTE and their treatment in frail patients.
      These patients could present several risk situations such as: chronic kidney
      disease (CKD), underweight or malnourished, falls, cognitive impairment, multi
      medicated patients, cancer and pregnancy. Guidelines typically recommend
      anticoagulation. There are multiple challenges in the safe use of anticoagulation
      in frail patients, including bleeding risk, monitoring and adherence, and
      polypharmacy. The objective of this review is to explore these at-risk situations
      and to suggest adequate anticoagulation therapy, when possible, in each of these
      complex situations.

PMID- 30217345
TI  - [A post-thrombotic pelvic congestion syndrome].
AB  - INTRODUCTION: Pelvic congestion syndrome is a chronic pelvic pain syndrome
      related to pelvic varices developed in the setting of primary venous
      insufficiency or secondary to venous obstruction. OBSERVATION: We report the case
      of a 35-year-old patient undergoing anticoagulant therapy for an extensive
      unprovoked left iliac vein thrombosis, who developed a disabling pelvic
      congestion syndrome secondary to chronic obstruction of the left iliac vein.
      Recanalization with stenting of the left iliac vein, combined with antithrombotic
      treatment with antiplatelet therapy (aspirin 100mg) and anticoagulation
      (rivaroxaban 20mg) for three months, followed by antiplatelet therapy alone, led
      to a complete and lasting regression of symptoms. DISCUSSION: Management of
      pelvic congestion syndrome secondary to post-thrombotic lesions must take into
      account its pathophysiology. It involves iliac venous angioplasty with stent
      placement in combination with antithrombotic therapy, which modalities remain to
      be specified in long-term follow-up.

PMID- 30217346
TI  - [Bilateral pulmonary embolism revealing granulomatosis with polyangiitis].
AB  - Granulomatosis with polyangiitis is a systemic small-vessels vasculitis. It is
      characterized by a granulomatous inflammatory reaction around the arterial wall
      and is, in most cases, accompanied by the presence of cytoplasmic - type anti
      neutrophil cytoplasmic antibodies (ANCA) with anti-proteinase 3 specificity. The
      predominant clinical presentation is frequent involvement of the upper and lower
      respiratory tract and the kidneys. This vasculitis is rarely revealed by
      pulmonary embolism. We report the observation of a 47-year-old male who presented
      with acute dyspnea. Chest X-ray disclosed an excavated opacity. Pulmonary
      angioscan revealed bilateral pulmonary embolism. The absence of clinical
      improvement after anticoagulant therapy with antibiotics and the presence of
      extra-respiratory signs led to the suspicion of a systemic inflammatory disease.
      The etiological investigations concluded with the diagnosis of granulomatosis
      with polyangiitis.

PMID- 30217347
TI  - [Hypothenar hammer syndrome: A recurrent case report after surgery].
AB  - Hypothenar hammer syndrome is a rare entity secondary to ulnar artery damage in
      the wrist, affecting mainly those exposed to repeated hand-palm trauma. Surgery
      is discussed in case of severe symptoms, resistant to medical treatment, and/or
      when anatomical lesions with emboligenic potential are demonstrated in the
      radiological exams. In this case, resection of the pathological zone with
      revascularization by autologous vein graft is the best option. We report the case
      of a 60-year-old patient who had a recurrence of symptoms more than 10 years
      after the completion of a surgical treatment. There was an aneurysmal thrombosed
      vein graft with extensive thrombus extending from the ulnar artery upstream of
      the Guyon's canal to the superficial palmar arch. The digital revascularization
      was provided by the radial superficial palmar arch and the presence of a
      collateral vascular supply. This late complication was responsible for
      compression of the ulnar nerve in Guyon's canal. A new surgery was performed
      consisting of the resection of the thrombosed zone, including the vein graft,
      without vascular reconstruction given the good vascularization of all the
      fingers, and release of the ulnar nerve to the wrist. The operative follow-up was
      uneventful with the disappearance of pain and sensory-motor deficits. Good
      digital vascularization was confirmed by imaging at 3 months postoperatively;
      nerve recovery by electromyogram at 6 months with normal conduction.

PMID- 30217348
TI  - [Thrombo-haemorrhagic disease-related hypoprothrombinemia-lupus anticoagulant
      syndrome revealing a light chains multiple myeloma].
AB  - Thrombosis and hemorrhage are two opposing manifestations of multiple myeloma.
      These hemostatic disorders are present in less than 12% of patients at diagnosis
      and involve various pathophysiological mechanisms. We report the case of a 39
      year-old patient with multiple myeloma revealed by the association of a
      hemorrhagic syndrome and deep vein thrombosis related to a hypoprothrombinemia
      anticoagulant lupus syndrome.

PMID- 30217349
TI  - A rare cause of abdominal pain: Fibromuscular dysplasia.
AB  - A 50-year-old man had a sudden severe abdominal pain. An abdominal enhanced
      computed tomographic scan revealed irregular stenosis of the celiac artery,
      dissection of the hepatic artery and of the left common iliac artery, and mid
      stenosis of the right renal artery with extended renal parenchymal hypodensity.
      After careful evaluation, the patient was diagnosed with fibromuscular dysplasia.
      Systematic head and neck CT angiography revealed right vertebral arterial
      stenosis and saccular aneurysm of the left vertebral artery. We have chosen
      conservative medical treatment for the multifocal fibromuscular dysplasia.

PMID- 30217350
TI  - [False aneurysm of the external iliac artery revealing Behcet's disease].
AB  - Behcet's disease is a vasculitis of unknown etiology. Vascular involvement is
      rare, but may be inaugural in many cases. We report a case of Behcet's disease
      revealed by a symptomatic pseudo-aneurysm of the external iliac artery. The
      symptomatology was non-specific. Ultrasound Doppler and computed tomographic
      angiography were essential for diagnosis. The pseudo-aneurysm was managed by
      endovascular treatment. Corticosteroid and immunosuppressant therapy were
      administrated after surgery.

PMID- 30217351
TI  - Physicians' comprehension of the German Patients' Rights Act: A cross-sectional
      study.
AB  - OBJECTIVE: The German Patients' Rights Act (PRA), promulgated on February 25,
      2013, was created to enhance transparency of patients' rights. This prospective
      study aimed to objectively measure physicians' comprehension of the PRA. METHODS:
      We generated a controlled study design, developing a questionnaire consisting of
      six case scenarios with 4-7 dichotomous items each. The survey concluded with
      seven 5-point-Likert scale questions, dealing with the PRA's effects. Physicians
      teaching at the Westfalische Wilhelms-Universitat (WWU) Munster served as the
      intervention group, and medical students from WWU Munster at the beginning of
      their clinical education formed the control group. Physicians were surveyed in
      November 2015; students were surveyed in February 2016. RESULTS: A total 56
      completed surveys of physicians and 134 of students were analyzed. Of a total 33
      points, on average physicians answered 21.04 (95% confidence interval (CI) 20.43
      21.64) items correctly, a significantly higher result than students' 19.74 (95%
      CI 19.31-20.17) points (p < 0.001; Hedges' g = 0.53). Estimations of the PRA's
      effects were ambiguous. Students agreed with the PRA's supporting effect more
      often than physicians (p < 0.001) whereas physicians felt increased uncertainty
      arising from the PRA. CONCLUSION: Comprehension of the PRA increases
      significantly over the course of medical work experience; however, this
      comprehension is limited among medical experts. The PRA leads to ambiguity and
      uncertainty in the medical decision-making process.

PMID- 30217352
TI  - Perceptions of caregivers and adolescents of the use of telemedicine for the
      child sexual abuse examination.
AB  - BACKGROUND: Childhood sexual abuse is a common cause of morbidity and mortality.
      All victims should receive a timely comprehensive medical exam. Currently there
      is a critical shortage of child abuse pediatricians who can complete the
      comprehensive child sexual abuse examination. Telemedicine has emerged as an
      innovative way to provide subspecialty care to this population. Despite the
      growing popularity of telemedicine, no literature exists describing patient and
      caregiver perceptions of telemedicine for this sensitive exam. OBJECTIVE: To
      explore caregiver and adolescent perspectives of the use of telemedicine for the
      child sexual abuse examination and discover factors that drive satisfaction with
      the technology. PARTICIPANTS AND SETTING: Caregivers and adolescents who
      presented for a child sexual abuse medical evaluation at our county's child
      advocacy center. METHODS: We completed semi structured interviews of 17
      caregivers and 10 adolescents. Guided by the Technology Acceptance Model
      interviews assessed perceptions about: general feelings with the exam, prior use
      of technology, feelings about telemedicine, and role of the medical team.
      Interviews were audio-recorded, transcribed, coded and analyzed using content
      analysis with constant comparative coding. Recruitment ended when thematic
      saturation was reached. RESULTS: There was an overwhelming positive response to
      telemedicine. Participants reported having a good experience with telemedicine
      regardless of severity of sexual abuse or prior experience with technology.
      Behaviors that helped patients and caregivers feel comfortable included a clear
      explanation from the medical team and professionalism demonstrated by those using
      the telemedicine system. CONCLUSION: Telemedicine was widely accepted by
      adolescents and caregivers when used for the child sexual abuse examination.

PMID- 30217353
TI  - Reply to "Is obesity a determinant of perioperative and postoperative outcome in
      patients following colorectal cancer surgery?"

PMID- 30217354
TI  - Is obesity a determinant of perioperative and postoperative outcome in patients
      following colorectal cancer surgery?

PMID- 30217355
TI  - Change in hazard rates of recurrence over time following diagnosis of endometrial
      cancer: An age stratified multicentre study from the FRANCOGYN group.
AB  - PURPOSE: Predicting the pattern of recurrence can aid in the development of
      targeted surveillance and treatment strategies. The objectives of this study were
      to identify patterns of recurrence in women with operable endometrial cancer (EC)
      and to identify high-risk periods for recurrence in function of age. PATIENTS AND
      METHODS: The data of 1153 women who received primary surgical treatment for stage
      I-III EC between January 2001 and December 2013 were abstracted from a
      prospectively maintained multicentre database. The time to first recurrence was
      calculated from the date of diagnosis, and the associated hazard function was
      examined to determine the peak risk period of recurrence. We categorized age at
      diagnosis as <65 and >= 65 years old and analysed the hazard rate (HR) by
      stratifying age groups. RESULTS: Women with EC aged >=65 years maintain a
      significant recurrence rate during follow-up whatever the stratification
      (locoregional recurrence, distant recurrence, ESMO/ESGO/ESTRO subgroup).
      Multivariable Cox proportional hazard regression showed that the increased risk
      of recurrence of EC was associated with advanced age, advanced disease
      ESMO/ESGO/ESTRO subgroup but not with initial treatment received. CONCLUSION: The
      annual HR of recurrence is not uniformly distributed over time but is dynamic and
      markedly determined by prognostic factors at diagnosis.

PMID- 30217356
TI  - Balancing Tricks and Mini-pigs: Steps along the Road to Propofol.

PMID- 30217357
TI  - What Makes a Piece of Art or Science a Masterpiece?
AB  - Works of art and science that achieve masterpiece status share several
      characteristics: they convey a special type of originality that captures the
      imagination, they stand the test of time, and they change the way artists or
      scientists think about their field.

PMID- 30217358
TI  - A Lifelong Passion for All Things Ribonucleic.
AB  - This year's Lasker-Koshland Special Achievement Award is given to Joan
      Argetsinger Steitz for her RNA research discoveries and her exemplary
      international leadership.

PMID- 30217359
TI  - Leading and Inspiring by Example.
AB  - Joan Steitz radiates a passion for science. Whether she's teaching an
      undergraduate course, mentoring a grad student or post-doc, or speaking at a
      scientific conference, her enthusiasm and curiosity for all things RNA is
      infectious. Joan, the recipient of the 2018 Lasker-Koshland Special Achievement
      Award in Medical Science, spoke with Cell editor (and her former post-doc) Lara
      Szewczak about how she came to be an advocate for women in science and shared
      advice for young scientists entering the research community today. Annotated
      excerpts from this conversation are presented below, and the full conversation is
      available with the article online.

PMID- 30217360
TI  - Histone Modifications: Insights into Their Influence on Gene Expression.
AB  - This year's Albert Lasker Basic Medical Research Award honors David Allis and
      Michael Grunstein for their pioneering research that highlighted the importance
      of histones and their post-translational modifications in the direct control of
      gene expression.

PMID- 30217362
TI  - Chasing Histone Biology from Sea Urchins to Yeast.
AB  - Together with David Allis, Michael Grunstein just received the Lasker Basic
      Medical research award. The article that follows is a transcript of a
      conversation with Jacques Deguine, scientific editor at Cell, that was edited for
      length. Annotated excerpts from this conversation are presented below, and the
      full conversation is available with the article online.

PMID- 30217361
TI  - Propofol: Milk of Amnesia.
AB  - This year's Lasker Clinical Research Award goes to James Baird Glen for the
      discovery and development of the anesthetic propofol. Patients benefit from its
      fast onset and rapid systemic clearance, eliminating the prolonged sedation
      effects experienced with earlier agents. In just 30 years, propofol has been
      adopted around the world for safe and controlled induction of anesthesia.

PMID- 30217363
TI  - Pursuing the Secrets of Histone Proteins: An Amazing Journey with a Remarkable
      Supporting Cast.

PMID- 30217364
TI  - Caviar tongue: A lingual physiological variation.

PMID- 30217365
TI  - [Endocrine disrupters: Towards an unsatisfying regulation].
AB  - Endocrine disruptors commonly make the headlines of newscasts and magazines,
      which is not without generating questions, even anxieties, with the general
      public. In a recent survey, 90% of French people considered it desirable to set
      up regulations concerning endocrine disruptors. However, under pressure from the
      lobbies of the chemical industry, and also due to scientific conflicts, the
      European Union is slow to legislate and has even been condemned before the
      European Court for failing to fulfill its obligations. This article does not
      intend to be exhaustive on the issue of endocrine disrupters, but rather to give
      the reader a certain number of keys enabling him to understand why national or
      European regulators are slow to establish specific regulation.

PMID- 30217366
TI  - A mixed method approach to understanding the factors surrounding delayed
      diagnosis of type one diabetes.
AB  - AIMS: This study examined delayed type one diabetes (T1D) diagnosis, along with
      the associated severity markers, in the United States. Qualitative reflection was
      explored to add depth of understanding. METHODS: 975 parents of a minor child
      with T1D were recruited through snowball, social media requests to complete a 55
      question online survey on the experience of diagnosis. RESULTS: 34% of children
      with T1D had a delayed diagnosis. When compared to those without a delayed
      diagnosis, these children were more likely to have an Emergency Room diagnosis
      (39.8% vs. 24.6%), be transported by ambulance or life flight (30.7% vs. 15.3%),
      be hospitalized (93.7% vs. 83.9%), spend time in an Intensive Care Unit (42.2%
      vs. 21.3%), and be in diabetic ketoacidosis (DKA) (42.2% vs. 21.3%). Younger
      children were at increased risk, with higher rates of DKA and fewer days of
      symptoms. Many parents experienced frustration receiving a prompt diagnosis for
      their child, including an inability to schedule a physician appointment, proper
      glucose testing, and concerns being dismissed by professionals. CONCLUSION: More
      physician and parent education is needed. Doctors should conduct glucose
      screenings when diabetes symptoms are present. Parents need education to
      recognize excessive thirst and frequent urination as reasons to seek medical
      treatment.

PMID- 30217367
TI  - Factors predicting reclassification of variants of unknown significance.
AB  - : Genetic variants of unknown significance (VUS) are an increasingly common
      result of genetic testing. VUS present dilemmas for treatment and surveillance.
      Family history may play a role in VUS reclassification over time. METHODS: All
      genetic tests performed at a tertiary referral center 2006-2015 were evaluated
      for the presence of VUS. Patients with VUS were evaluated for demographics,
      clinical characteristics, family history, and gene characteristics. RESULTS: In
      total, 2291 individuals were tested from 1639 families; 150 VUS were identified.
      Twenty-eight VUS reclassified, 21 to benign and 7 to pathogenic. Logistic
      regression demonstrated the number of family members with associated phenotypic
      disease was a significant predictor of reclassification. CONCLUSION: The
      likelihood of VUS reclassification can be predicted by increased positive family
      history of disease. Most VUS reclassify to benign, but one-fourth reclassify to
      pathogenic. The actual risk of a VUS should be assessed based on family history
      and routinely checked for reclassification.

PMID- 30217368
TI  - Plasmapheresis-A lifesaving treatment for life threatening HELLP syndrome.

PMID- 30217369
TI  - Genomics to immunotherapy of ovarian clear cell carcinoma: Unique opportunities
      for management.
AB  - Ovarian clear cell carcinoma (OCCC) is distinctive from other histological types
      of epithelial ovarian cancer, with genetic/epigenetic alterations, a specific
      immune-related molecular profile, and epidemiologic associations with ethnicity
      and endometriosis. These findings allow for the exploration of unique and
      specific treatments for OCCC. Two major mutated genes in OCCC are PIK3CA and
      ARID1A, which are frequently coexistent with each other. Other genes' alterations
      also contribute to activation of the PI3K (e.g. PIK3R1 and PTEN) and
      dysregulation of the chromatin remodeling complex (e.g. ARID1B, and SMARKA4).
      Although the number of focal copy number variations is small in OCCC,
      amplification is recurrently detected at chromosome 20q13.2 (including ZNF217),
      8q, and 17q. Both expression and methylation profiling highlight the significance
      of adjustments to oxidative stress and inflammation. In particular, up-regulation
      of HNF-1beta resulting from hypomethylation contributes to the switch from
      anaerobic to aerobic glucose metabolism. Additionally, up-regulation of HNF-1beta
      activates STAT3 and NF-kappaB signaling, and leads to immune suppression via
      production of IL-6 and IL-8. Immune suppression may also be induced by the
      increased expression of PD-1, Tim-3 and LAG3. Mismatch repair deficient
      (microsatellite instable) tumors as found in Lynch syndrome also induce immune
      suppression in some OCCC. In a recent phase II clinical trial in heavily-treated
      platinum-resistant ovarian cancer, two out of twenty cases with a complete
      response to the anti-PD-1 antibody, nivolumab, were OCCC subtypes. Thus, the
      immune-suppressive state resulting from both genetic alterations and the unique
      tumor microenvironment may be associated with sensitivity to immune checkpoint
      inhibitors in OCCC. In this review, we highlight recent update and progress in
      OCCC from both the genomic and immunologic points of view, addressing the future
      candidate therapeutic options.

PMID- 30217370
TI  - Relationship of Red Cell Distribution Width to Adverse Outcomes in Adults With
      Congenital Heart Disease (from the Boston Adult Congenital Heart Biobank).
AB  - Red cell distribution width (RDW), a measure of variability in red cell size,
      predicts adverse outcomes in acquired causes of heart failure. We examined the
      relation of RDW and outcomes in adults with congenital heart disease. We
      performed a prospective cohort study on 696 ambulatory patients >=18years old
      enrolled in the Boston Adult Congenital Heart Disease Biobank between 2012 and
      2016 (mean age 38.7 +/- 13.5 years; 49.9% women). The combined outcome was all
      cause mortality or nonelective cardiovascular hospitalization. Most patients had
      moderately or severely complex congenital heart disease (42.5% and 38.5%,
      respectively). Mean RDW was 14.0 +/- 1.3%. RDW >15% was present in 81 patients
      (11.6%). After median 767days of follow-up, 115 patients sustained the primary
      combined outcome, including 31 who died. Higher RDW predicted both the combined
      outcome (hazard ratio [HR] for RDW >15% = 4.5, 95% confidence interval [CI] 3.0
      to 6.6; HR per + 1SD RDW = 1.8, 95% CI 1.6 to 2.0, both p <0.0001) and death
      alone (HR for RDW >15% = 7.1, 95% CI 3.5 to 14.4; HR per + 1SD RDW = 1.8, 95% CI
      1.6 to 2.0, both p <0.0001). RDW remained an independent predictor of the
      combined outcome after adjusting for age, cyanosis, congenital heart disease
      complexity, ventricular systolic function, New York Heart Association functional
      class, hemoglobin concentration, mean corpuscular volume, high-sensitivity C
      reactive protein and estimated glomerular filtration rate (HR per + 1SD RDW =
      1.5, 95% CI 1.2 to 1.9, p <0.0001). RDW also remained an independent predictor of
      mortality alone after adjustment for age plus each variable individually. In
      conclusion, elevated RDW is an independent predictor of all-cause mortality or
      nonelective cardiovascular hospitalization in adults with congenital heart
      disease. This simple clinical biomarker identifies increased risk for adverse
      events even among patients with preserved functional status.

PMID- 30217371
TI  - Comparison of Effectiveness of Azilsartan Medoxomil and Olmesartan in Blacks
      Versus Whites With Systemic Hypertension.
AB  - Two post hoc analyses in self-identified black and white patients with
      hypertension evaluated the angiotensin II receptor blocker azilsartan medoxomil
      (AZL-M) and the fixed-dose combination of AZL-M with chlorthalidone (AZL-M/CLD)
      versus the ARB olmesartan (OLM) and the OLM fixed-dose combination with
      hydrochlorothiazide (OLM/HCTZ). One analysis pooled 1,610 patients from two 6
      week randomized controlled trials to compare once daily AZL-M 40 mg, AZL-M 80 mg,
      OLM 40 mg, and placebo. The second analysis included 1,020 patients from a 12
      week randomized controlled trial to compare once daily AZL-M/CLD 40/25 mg, AZL
      M/CLD 80/25 mg, and OLM/HCTZ 40/25 mg. Efficacy end points were 24-hour mean
      ambulatory and clinic systolic and diastolic blood pressure (SPB/DBP) and the
      percentage of patients achieving clinic SBP/DBP targets. Treatment with AZL-M 80
      mg lowered mean clinic SBP by 12.5 mm Hg (p <0.01 vs OLM), treatment with AZL
      M/CLD 40 mg/25 mg lowered mean ambulatory SBP by 31.0 mm Hg and mean clinic SBP
      by 39.3 mm Hg (both p <0.05 vs OLM/HCTZ), and treatment with AZL-M/CLD 80 mg/25
      mg lowered mean ambulatory SBP by 34.4 mm Hg (p <0.01 vs OLM/HCTZ) and mean
      clinic SBP by 39.2 mm Hg (p <0.05 vs OLM/HCTZ). Target BP goals were achieved
      more frequently with AZL-M versus OLM and with AZL-M/CLD versus OLM/HCTZ. In
      conclusion, in both black and white patients, BP was lowered more effectively
      with AZL-M versus OLM and with AZL-M/CLD versus OLM/HCTZ. The AZL-M/CLD 40 mg/25
      mg combination resulted in a statistically significant reduction in BP in both
      black and white patients.

PMID- 30217372
TI  - Comparison of Outcomes and Cost of Endovascular Management Versus Surgical Bypass
      for the Management of Lower Extremities Peripheral Arterial Disease.
AB  - The management of lower extremities peripheral arterial disease (LE-PAD) has
      always been debatable. We sought to explore in-hospital outcomes in
      hospitalizations that underwent endovascular or bypass surgery for LE-PAD from
      nation's largest, publicly available database. The National Inpatient Sample from
      2012 to 2014 was queried to identify adult hospitalizations underwent
      endovascular management and bypass surgery for LE-PAD. Appropriate International
      Classification of Diseases, Ninth Revision, Clinical Modification diagnostic and
      procedural codes were utilized to identify hospitalizations. A total of 89,256
      hospitalizations were identified having endovascular management or bypass surgery
      for LE-PAD. More hospitalizations underwent endovascular intervention as compared
      with bypass surgery. Overall, hospitalizations for endovascular management had
      higher baseline co-morbidities and older age. A propensity score matched analysis
      was performed to compare in-hospital outcomes. After matching, 28,791
      hospitalizations were included in each group. In-hospital mortality was
      significantly lower with endovascular intervention procedure as compared with
      surgical bypass group (1.5% vs 2.5%, p <=0.001). All other secondary outcomes
      were noted lower with endovascular management except stroke and postprocedural
      infection. Taken together, these may account for higher discharges to home, lower
      length of stay, and less cost of hospitalizations associated with endovascular
      management. In conclusion, endovascular management is associated with lower in
      hospital morbidity, mortality, length of stay, and cost when compared with bypass
      surgery in this study.

PMID- 30217373
TI  - Usefulness of Global Longitudinal Strain for Early Identification of Subclinical
      Left Ventricular Dysfunction in Patients With Active Cancer.
AB  - Cardiotoxicity from cancer therapy has become a leading cause of morbidity and
      mortality in cancer survivors. The most commonly used definition is cancer
      therapeutic related cardiac dysfunction defined as a left ventricular ejection
      fraction (LVEF) reduction of >10%, to a value below 50%. However, according to
      the recent American and European Society of Echocardiography, global longitudinal
      strain (GLS) is the optimal parameter for early detection of subclinical left
      ventricular dysfunction. The objective of this study was to evaluate the
      frequency of GLS reduction in patients with active cancer and its correlation to
      other echocardiographic parameters. Data were collected as part of the
      International Cardio-Oncology Registry. All patients performed at least 2
      echocardiograms including GLS. We evaluated the frequency of GLS reduction (>=10%
      relative reduction), its correlation to LVEF reduction and whether there are
      other predicting echocardiographic parameters. In 64 consecutive patients, 12
      (19%) had >=10% GLS relative reduction, of which 75% had no concomitant ejection
      fraction reduction. There were no significant differences in the baseline cardiac
      risk factors (hypertension, diabetes, hyperlipidemia, or smoking). Treatment with
      Doxorubicin, Pertuzumab, or Ifosfamide was significantly more frequent in
      patients GLS reduction. No other echocardiographic parameters, including
      diastolic function or systolic pulmonary artery pressure were significant
      predictors for GLS reduction. In conclusion, our study demonstrates that GLS
      reduction is frequent in active cancer patients, precedes LVEF reduction and
      cannot be anticipated by other echocardiographic parameters. Using GLS routinely
      during therapy may lead to an early diagnosis of cardiotoxicity.

PMID- 30217374
TI  - Performance of One- Compared With Two-Catheter Concepts in Transradial Coronary
      Angiography (from the Randomized Use of Different Diagnostic Catheters-Radial
      Trial).
AB  - The Use of Different Diagnostic Catheters-Radial-Trial sought to compare the
      safety and efficacy of one-catheter concepts (OCC) using Tiger II or BLK
      catheters with two-catheter concepts (TCC) using standard Judkins catheters for
      transradial coronary angiography. A total of 300 patients planed for coronary
      angiography were enrolled into this single-center, single-blinded trial. Patients
      were randomized in a 2:1 ratio to either OCC by Tiger II (n = 100) and BLK (n =
      100) or TCC by Judkins (n = 100) catheters. Primary end point was time required
      to perform a complete coronary angiography. Coronary angiography duration was 603
      +/- 29 seconds and 552 +/- 26 sec in the OCC and the TCC groups (p = 0.052).
      Fluoroscopy time was longer in the OCC (408 +/- 28 sec) as compared with the TCC
      group (258 +/- 28 sec, p = 0.009) and the amount of contrast volume used
      significantly higher (98 +/- 5 ml vs 67 +/- 4 ml, p < 0.001). Crossover rates
      were increased in the OCC as compared with the TCC group (37% vs 4%, p < 0.001).
      These effects were observed irrespective of OCC catheter type. In conclusion,
      this study demonstrates that OCC do not reduce angiography time, but are
      associated with an increased amount of contrast volume and longer fluoroscopy
      time as compared with TCC.

PMID- 30217375
TI  - Effect of Pitavastatin Compared with Atorvastatin andRosuvastatin on New-Onset
      Diabetes Mellitus in PatientsWith Acute Myocardial Infarction.
AB  - Although statin use in patients with acute myocardial infarction (AMI) is
      mandatory, it has been suggested to be associated with new-onset diabetes
      mellitus (NODM). In real world practice, moderate-intensity statin therapy is
      more commonly used than high-intensity statin therapy. In this study, we
      investigated the impact of moderate-intensity pitavastatin (2 to 4 mg) compared
      with moderate-intensity atorvastatin (10 to 20 mg) and rosuvastatin (5 to 10 mg)
      on the development of NODM during a follow-up period of up to 3years. Between
      November 2011 and May 2015, 2001 patients with AMI who did not have diabetes
      mellitus were investigated. The cumulative incidence of NODM was evaluated in all
      groups. To adjust for potential confounders, multinomial propensity scores were
      used. Cox proportional hazard models were used to assess the hazard ratio of NODM
      in the atorvastatin and rosuvastatin groups compared with pitavastatin group. The
      cumulative incidence of NODM was significantly lower in pitavastatin group
      compared with the atorvastatin and rosuvastatin groups (3.0% vs 8.4% vs 10.4%,
      respectively; Log-rank p value = 0.001). After weighting the baseline
      characteristics of the 3 statin groups by multinomial propensity scores,
      atorvastatin (hazard ratio: 2.615, 95% confidence interval: 1.163 to 5.879) and
      rosuvastatin (hazard ratio: 3.906, 95% confidence interval: 1.756 to 8.688) were
      found to be associated with a higher incidence of NODM compared with pitavastatin
      therapy on multivariable analysis. Moderate-intensity pitavastatin therapy is
      associated with a lower incidence of NODM in patients with AMI andhas similar
      clinical outcomes to moderate-intensity atorvastatin and rosuvastatin therapy.

PMID- 30217376
TI  - Lifetime Pattern of Atrial Fibrillation and the Risks of Stroke and Death in a
      Population-based Cohort of Men (from The Manitoba Follow-Up Study).
AB  - Atrial fibrillation (AF) is associated with stroke and mortality. The arrhythmia
      can be sustained or intermittent. Previous studies that have used fixed
      covariates and short-time horizons to examine the relation between the pattern of
      AF and the occurrence of events have produced conflicting results. The Manitoba
      Follow-Up Study includes 3,983 originally healthy men who have been followed with
      routine examinations since 1948. AF status during each visit was classified into
      the following patterns: free of AF, newly diagnosed; intermittent AF-in
      sinus;intermittent AF-in AF; sustained AF. We created adjusted Cox proportional
      hazards models with time-dependent covariates to estimate risks for stroke and
      death according to AF pattern. After 167,982 person-years of follow-up and 66,297
      electrocardiograms (ECGs), 548 men had at least 1 ECG documenting AF, 799 had a
      stroke, and 3173 died. Relative to men free of AF, sustained and newly diagnosed
      AF were associated with stroke (hazard ratio [HR] 1.85, 95% confidence interval
      [CI] 1.33 to 2.59 and HR 1.71, 95% CI 1.10 to 2.66, respectively) and death (HR
      2.48, 95% CI 2.11 to 2.92 and HR 2.03, 95% CI 1.64 to 2.52, respectively).
      Intermittent AF was associated with death (HR 2.41 95% CI 1.58 to 3.68 in AF and
      HR 1.71 95% CI 1.44 to 2.03 in sinus), but not with stroke (HR 0.68, 95% CI 0.22
      to 2.13 in AF and HR 1.02 95% CI 0.72 to 1.45 in sinus). Antithrombotic therapy
      was associated with a reduced risk of the outcomes. In conclusion, longitudinal
      analysis of patterns of AF evolving over time provided evidence that the
      associated risks of stroke and death vary considerably with rhythm classification
      on serial ECGs.

PMID- 30217377
TI  - Feasibility of a Smartphone-enabled Cardiac Rehabilitation Program in Male
      Veterans With Previous Clinical Evidence of Coronary Heart Disease.
AB  - Cardiac rehabilitation (CR) is recommended for patients with coronary heart
      disease, however, participation among veterans remains poor. Smartphones may
      facilitate data transfer and communication between patients and providers, among
      other benefits. We evaluated the feasibility of a smartphone-enabled CR program
      in a population of veterans. Qualifying veterans were prospectively enrolled in a
      single-arm, nonrandomized feasibility study of a smartphone-enabled, home-based
      CR program, featuring an app with daily reminders to exercise, log vitals, and
      review educational materials. A coach remotely monitored patients through an
      online dashboard and scheduled telephone visits. Clinical end points were
      assessed as an exploratory aim. After 21 veterans provided informed consent, 18
      were enrolled and successfully completed at least 30days of the program; 13
      completed the entire 12-week intervention. Mean (standard deviation) age was 62
      (7) years and 96% were male. Program completers logged a mean (standard
      deviation) of 3.5 (1.4) exercise sessions and 150 (86) exercise minutes per week.
      The majority (84%) of program completers reported being satisfied overall with
      the program. Mean functional capacity improved by 1.0 metabolic equivalents (5.3
      to 6.3, 95% confidence interval 0.3 to 1.7; p = 0.008) and mean systolic blood
      pressure at rest improved by 9.6mm Hg (mean difference 9.6, 95% confidence
      interval -19.0 to -0.7; p = 0.049) among completers. Smartphone-enabled, home
      based CR is feasible in veterans with heart disease and is associated with
      moderate to high levels of engagement and patient satisfaction.

PMID- 30217378
TI  - D-Dimer Levels and Effect of Rivaroxaban on Those Levels and Outcomes in Patients
      With Acute Coronary Syndrome (An ATLAS ACS-TIMI 46 Trial Substudy).
AB  - D-dimer has been used as both a diagnostic and prognostic biomarker in the
      assessment of patients with venous thromboembolism, but its prognostic value in
      the setting of arterial acute coronary syndromes (ACS) and the ability of
      pharmacotherapy to reduce D-dimer in ACS is less well characterized. It was
      hypothesized that elevated baseline D-dimer would be associated with poor
      clinical outcomes in ACS, and that Factor Xa inhibition with Rivaroxaban would
      reduce D-dimer acutely and chronically. The ATLAS ACS TIMI-46 trial assessed the
      safety and efficacy of rivaroxaban compared with placebo in ACS patients. A
      subset of subjects had a D-dimer measured at baseline (n = 1,834, 52.5%). A
      univariate and multivariable logistic regression assessed the relation between
      baseline D-dimer and a composite end point of cardiovascular death, myocardial
      infarction, or stroke through 6 months. The Wilcoxon rank sum test was used to
      compare change in D-dimer level between the treatment groups from baseline.
      Baseline D-dimer was associated with the composite efficacy outcome in a
      univariate logistic regression (odds ratio 1.15, 95% confidence interval 1.03 to
      1.29, p = 0.015) and a multivariable logistic regression (odds ratio 1.13, 95%
      confidence interval 1.00 to 1.28, p = 0.048). Rivaroxaban administration lowered
      D-dimer levels compared wth placebo after administration of the first dose of
      study drug (p = 0.026), at day 30 (p < 0.001) and day 180 (p < 0.001). In
      conclusion, elevated baseline D-dimer was associated with an increased risk of
      the composite outcome within 6 months of the ACS event and administration of the
      Factor Xa inhibitor rivaroxaban was associated with lower D-dimer levels compared
      with placebo after the first dose, at day 30 and day 180.

PMID- 30217379
TI  - Presynaptic Calcium En Passage through the Axon.

PMID- 30217380
TI  - Nonlinear Elasticity of the ECM Fibers Facilitates Efficient Intercellular
      Communication.
AB  - Biological cells embedded in fibrous matrices have been observed to form
      intercellular bands of dense and aligned fibers through which they mechanically
      interact over long distances. Such matrix-mediated cellular interactions have
      been shown to regulate various biological processes. This study aimed to explore
      the effects of elastic nonlinearity of the fibers contained in the extracellular
      matrix (ECM) on the transmission of mechanical loads between contracting cells.
      Based on our biological experiments, we developed a finite-element model of two
      contracting cells embedded within a fibrous network. The individual fibers were
      modeled as showing linear elasticity, compression microbuckling, tension
      stiffening, or both of the latter two. Fiber compression buckling resulted in
      smaller loads in the ECM, which were primarily directed toward the neighboring
      cell. These loads decreased with increasing cell-to-cell distance; when cells
      were >9 cell diameters apart, no such intercellular interaction was observed.
      Tension stiffening further contributed to directing the loads toward the
      neighboring cell, though to a smaller extent. The contraction of two neighboring
      cells resulted in mutual attraction forces, which were considerably increased by
      tension stiffening and decayed with increasing cell-to-cell distances. Nonlinear
      elasticity contributed also to the onset of force polarity on the cell
      boundaries, manifested by larger contractile forces pointing toward the
      neighboring cell. The density and alignment of the fibers within the
      intercellular band were greater when fibers buckled under compression, with
      tension stiffening further contributing to this structural remodeling. Although
      previous studies have established the role of the ECM nonlinear mechanical
      behavior in increasing the range of force transmission, our model demonstrates
      the contribution of nonlinear elasticity of biological gels to directional and
      efficient mechanical signal transfer between distant cells, and rehighlights the
      importance of using fibrous gels in experimental settings for facilitating
      intercellular communication. VIDEO ABSTRACT.

PMID- 30217382
TI  - A gas chromatography full scan high resolution Orbitrap mass spectrometry method
      for separation and characterization of 3-hydroxymethyl pyridine ester of fatty
      acids at low levels.
AB  - Fatty acid methyl esters (FAMEs), which are commonly used to characterize lipids,
      have several limitations to conclude on many structures. 3-Pyridylcarbinol esters
      (3-PCE) are used to characterize fatty acid structures [1], in particular, to
      identify ring and double bond positions on the carbon chain. Chromatographic
      separation of these esters is complex due to their polarity and high boiling
      points. In this study, we used a column with high resolutive power based on ionic
      liquids to increase the separation quality in gas chromatography (GC). In
      addition, we used a high-resolution detector (Orbitrap) to limit non-specific
      signals and improve the detection limits. This detector could be used with a mass
      filter at 5 ppm for the rapid determination of 3-PCE from its characteristic ions
      (m/z = 108.0441 and 92.0495). This filter allowed the identification of
      derivative fatty acids with good sensibility. Thus, it was possible to
      characterize 3-PCE by measuring the exact fragment masses to confirm structures
      such as C19:2n12cycloDelta9.

PMID- 30217381
TI  - When More Is Less: Dual Phosphorylation Protects Signaling Off State against
      Overexpression.
AB  - Kinases in signaling pathways are commonly activated by multisite
      phosphorylation. For example, the mitogen-activated protein kinase Erk is
      activated by its kinase Mek by two consecutive phosphorylations within its
      activation loop. In this article, we use kinetic models to study how the
      activation of Erk is coupled to its abundance. Intuitively, Erk activity should
      rise with increasing amounts of Erk protein. However, a mathematical model shows
      that the signaling off state is robust to increasing amounts of Erk, and Erk
      activity may even decline with increasing amounts of Erk. This counterintuitive,
      bell-shaped response of Erk activity to increasing amounts of Erk arises from the
      competition of the unmodified and single phosphorylated form of Erk for access to
      its kinase Mek. This shows that phosphorylation cycles can contain an intrinsic
      robustness mechanism that protects signaling from aberrant activation e.g., by
      gene expression noise or kinase overexpression after gene duplication events in
      diseases like cancer.

PMID- 30217383
TI  - Application of quantitative analysis of multi-component system approach for
      determination of ginsenosides in different mass-spectrometric conditions.
AB  - The lack of standard substances is a bottleneck for quality control in
      traditional and alternative medicine. Development of the HPLC-UV approaches
      combined with single standard for quantitative analysis of multi-component system
      (QAMS) allowed determination of several plant biomarkers by implementation of the
      relative response factors (RRFs). Robustness and ruggedness of such methods are
      commonly demonstrated by performing the analysis in changing analytical
      conditions on the different HPLC equipment and columns. The nature of MS
      detection is much more complicated and dependent on the instrumentation.
      Therefore, this study was conducted to justify the use of RRFs for HPLC-MS
      determination of bioactive compounds from plants. Protopanaxatriol (PPT),
      protopanaxadiol (PPD) and ocotillol (OT) ginseng saponins (ginsenosides) were
      successfully separated on a reversed-phase PFP-column with high group
      selectivity. Fragmentation patterns for these groups of compounds were
      established on different HPLC-ESI-MS systems and at varied declustering
      potentials (DPs). The use of sapogenin fragmentation ions in positive detection
      mode along with group reference standards was shown to be an optimal way to
      perform quantification. The performance of the developed group targeted HPLC-MS
      QAMS approach was tested in the course of measurements conducted on the different
      instrumentation. The differences between QAMS and external standard method (ESM)
      quantification results were below 15% for all determined saponins.

PMID- 30217384
TI  - Miniaturized micromachined gas chromatography with universal and selective
      detectors for targeted volatile compounds analysis.
AB  - An effective analytical strategy for targeted analysis of volatile organic
      compounds which combines two orthogonal separation mechanisms and multiple
      tunable detection in a compact transportable analytical system is introduced.
      This strategy uses a commercially available micromachined gas chromatograph
      comprising a micromachined on-board thermal conductivity detector. The
      chromatograph capability is enhanced by incorporating a modified diode array
      detector and a radio frequency modulated ion mobility spectrometry
      microfabricated electromechanical system. The analytical platform offers powerful
      detection capabilities of individual compounds and various classes of volatile
      organic compounds with improved provisional confirmatory capability. The
      transportable micromachined gas chromatograph employs field replaceable
      conventional capillary columns for the separation of analytes. The use of a
      silicon micromachined sample introduction device affords fast injection to
      minimize band broadening with fast chromatographic separation rendered in the
      order of minutes. Advantaged synergy also includes leveraging the resolving power
      of gas chromatography to minimize charge exchange in the ionization chamber of
      the differential mobility spectrometer for improved detector performance.
      Performance of this scalable and transportable analytical system is demonstrated
      with relevant volatile compounds such as acetaldehyde, acetone, carbon disulfide,
      benzene, and ethyl butyrate having a day-to-day variability less than 5% and with
      a high degree of reliability.

PMID- 30217385
TI  - Updates to the compensation plan for pharmacy services in Alberta, Canada.

PMID- 30217386
TI  - Corneal morphology and visual outcomes in LASIK patients after orthokeratology: A
      pilot study.
AB  - A STATEMENT OF SIGNIFICANCE: For the first time, this study shows that corneas
      that previous undergone orthokeratology treatment do not respond differently to
      LASIK compared with previous soft contact lens wear experience. PURPOSE: To
      evaluate and compare the corneal morphology and visual outcomes of long-term soft
      and orthokeratology (OK) contact lens fitting in wearers undergoing corneal
      refractive surgery (LASIK) for myopia correction. METHODS: Sixteen (16) myopic
      patients wearing hydrophilic soft contact lens (SCL, n = 8 subjects, control
      group) and OK (n = 8 subjects, OK group) lenses who undergone LASIK were
      retrospectively evaluated. Preoperative fitting of contact lenses and one year
      postoperative were studied using Pentacam (Oculus, Inc. GmbH, Wetzlar, Germany).
      Corneal pachymetry and volume, corneal topography, anterior and posterior surface
      elevation data and the anterior surface aberrometry of the cornea were recorded
      and used for fitting. RESULTS: Age, refractive error and topographic parameters
      before LASIK did not showed statistically significant differences between the two
      study groups. LASIK post-treatment results showed identical changes in both
      control and OK groups and did not show significant differences in all the
      parameters evaluated. The changes on corneal parameters and HOA due to refractive
      surgery intervention were not different between Control and OK group (p > 0.050).
      CONCLUSIONS: Corneal changes due to OK treatment are reversible after its
      discontinuation. The present study gives an overview of how OK does not impair
      future LASIK surgery for the correction of myopia and does not influence the
      success/results of such intervention. These findings suggest that OK CL wear does
      not change corneal biomechanics and does not compromise a possible LASIK
      refractive surgery. Although this is a pilot study and there is a need of
      evaluate this results/changes in future studies.

PMID- 30217387
TI  - Lifelong learning and productive aging among the baby-boomers in Singapore.
AB  - Coined in 1982, the term productive aging is commonly associated with active
      participation in work, although it has since expanded beyond employment to
      include other dimensions of work, such as volunteering, caregiving and other
      activities that "produce(s) good/service for society, whether paid or unpaid"
      (Caro, Bass and Chen, 1993, p. 6). In this paper focusing on examining lifelong
      learning as one of the other activities in what comprises productive aging, we
      seek to explore the connections of lifelong learning to the notions of productive
      aging from the perspective of baby-boomers in Singapore. Using data from the
      qualitative study of Lifelong Learning among Older Adults in Singapore, which
      included 64 interviews with learners and non-learners of the baby-boomer
      generation (age 50-64), we first explore the grounded meanings of productive
      aging as articulated through lifelong learning. Next, we examine the benefits of
      lifelong learning as perceived by the baby-boomers, in particular, focusing on
      general wellbeing in enhancing productive aging. This is followed with a section
      examining barriers to lifelong learning to provide insight into deterrence to
      learning. Through the discussion of older adults' perceptions on lifelong
      learning and their engagement or lack of engagement especially with formal and
      non-formal learning, we hope to provoke a further re-thinking of what constitutes
      being productive in later life. Finally, we argue that beyond just another
      component to productive aging, lifelong learning should perhaps be further
      recognized as an enabler contributing to capacity-building of the other
      components including economic production, family care and volunteer services in
      enhancing productive aging.

PMID- 30217388
TI  - A Newly Discovered Manuscript of Charles T. Jackson, MD, on the Preparation and
      Administration of Anesthetics for Humans and Animals.
AB  - A newly discovered handwritten manuscript of Charles T. Jackson, MD, contains
      instructions for the preparation and administration of sulfuric ether,
      information on Jackson's preferred mixture of ether and chloroform, an account of
      his experiments with other potential anesthetic agents, and his comments on
      etherizing cattle and other animals. Jackson's nine-page manuscript is believed
      to have been written in the autumn of 1851, around the time that he submitted his
      memorial on the discovery of etherization to Baron von Humboldt, and made a
      separate submission to the US Congress.

PMID- 30217389
TI  - Charles Burstein, MD: First Director of Anesthesiology at Hospital for Special
      Surgery.
AB  - Charles L. Burstein was the first departmental Director and Chief of
      Anesthesiology at the Hospital for Special Surgery in New York City. He joined
      the staff in 1937, when the hospital was still known by its original name of the
      Hospital for the Ruptured and Crippled. In 1940, it was renamed The Hospital for
      Special Surgery. Burstein, an early disciple of Emery Rovenstine, accomplished
      much to advance the Department of Anesthesiology through academic collaborations,
      education, clinical specialization, and research. He laid the groundwork for the
      future success of a department that continues to thrive to this day in clinical
      and academic orthopedic anesthesia.

PMID- 30217390
TI  - Was Mafeisan an Anesthetic in Ancient China?
AB  - According to the Chinese historical books, Records of the Three Kingdoms () and
      Book of the Later Han (), Hua Tuo (, 140 - 208), a Traditional Chinese medicine
      (TCM) physician invented Mafeisan, an oral herbal general anesthetic, more than
      1800 years ago during Eastern Han Dynasty. However, no written record of
      ingredients of the original Mafeisan has been found anywhere so far although
      there have been several similar anesthetic prescriptions published in TCM books
      later. There has been controversy over the existence of Mafeisan and even Hua Tuo
      in Chinese literature. We did extensive literature search and analysis, and
      believe that there indeed was Mafeisan in Hua Tuo's time.

PMID- 30217391
TI  - The Legacy of Eve's Curse: Religion, Childbirth Pain, and the Rise of Anesthesia
      in Europe: c. 1200-1800s.

PMID- 30217392
TI  - Related Gunmen Paddock Committed Murder-Suicide in 1888 and in 2017.
AB  - Genealogical and periodical research reveals that two distantly related gunmen
      surnamed Paddock, a retired dentist-anesthetist and a retired accountant,
      committed murder-suicide in 1888 and in 2017, respectively.

PMID- 30217393
TI  - From Dental to Mental Institutions: Elmer McKesson's Secondary Saturation with
      Nitrous Oxide.
AB  - As popularized by Elmer McKesson, MD, "secondary saturation" with nitrous oxide
      could expose patients to a second burst of 100% laughing gas to relax their
      muscles to assist surgeons. On rare occasions, this technique could provide a
      second opportunity for hypoxic brain damage and possible admission
      postoperatively to insane asylums.

PMID- 30217394
TI  - Insights into the diagnosis and pathogenesis of the antiphospholipid syndrome.
AB  - The Antiphospholipid syndrome (APS), formerly known as Anticardiolipin or Hughes
      syndrome, is a systemic autoimmune disorder characterized by obstetrical
      complications and thrombotic events affecting almost every organ-system in
      patients persistently testing positive for antiphospholipid antibodies (aPL). The
      contribution of the extra-criteria aPL to the pathogenesis of APS have exceeded
      the expectations of a simple, direct pathologic 'hit' leading to thrombogenesis
      or obstetrical complications, and more pathologic pathways are being linked
      directly or indirectly to aPL. The value of extra-criteria aPL is on the rise,
      and these antibodies are nowadays evaluated as markers for risk assessment in the
      diagnostic approach to APS. A diagnosis of APS should be considered in pediatric
      patients with suggestive clinical and laboratory picture. Management of APS
      remains mostly based on anticoagulation, while other drugs are being tested for
      efficacy and side effects. Low-dose aspirin may have a role in the management of
      thrombotic and obstetric APS. Due to the high variability in disease severity and
      complication recurrence outcomes, new tools are being developed and validated to
      assess the damage index and quality of life of APS patients.

PMID- 30217395
TI  - Double plication for spring-mediated in-continuity intestinal lengthening in a
      porcine model.
AB  - BACKGROUND: Short bowel syndrome is a condition with substantial morbidity and
      mortality, yet definitive therapies are lacking. Distraction enterogenesis uses
      mechanical force to "grow" new intestine. In this study, we examined whether
      intestinal plication can be used to safely achieve spring-mediated intestinal
      lengthening in a functioning segment of jejunum in its native position. METHODS:
      A total of 12 juvenile, miniature Yucatan pigs underwent laparotomy to place
      either compressed springs or expanded springs within a segment of jejunum (n = 6
      per group). The springs were secured within the jejunum by performing intestinal
      plication to narrow the intestinal lumen around the spring. After 3 weeks, the
      jejunum was retrieved and examined for lengthening and for histologic changes.
      RESULTS: There were no intraoperative or postoperative complications, and the
      pigs tolerated their diets and gained weight. Segments of jejunum containing
      expanded springs showed no significant change in length over the 3 weeks. In
      contrast, jejunum containing compressed springs showed nearly a 3-fold increase
      in length (P < .001). Histology of the retrieved jejunum showed a significant
      increase in thickness of the muscularis propria and in crypt depth relative to
      normal jejunum. CONCLUSION: Intestinal plication is effective in securing
      endoluminal springs to lengthen the jejunum. This approach is a clinically
      relevant model because it allows for normal GI function and growth of animals
      during intestinal lengthening, which may be useful in lengthening intestine in
      patients with short bowel syndrome.

PMID- 30217396
TI  - Emergent groin hernia repair: A single center 10-year experience.
AB  - BACKGROUND: Emergent groin hernia repair can be a challenging clinical scenario.
      We aimed to evaluate the perioperative and long-term outcomes of emergent groin
      hernia repair at our institution over the last 10 years, with particular interest
      in surgical approach and mesh use for such cases. METHODS: Adult patients who
      underwent emergent groin hernia repair from 2005-2015 were retrospectively
      reviewed. Outcomes included surgical site infections, perioperative
      complications, readmissions, reoperations, mortality, and long-term hernia
      recurrence. Predictors of surgical site infection and perioperative complications
      were investigated using multivariate logistic regression. RESULTS: A total of 257
      patients met inclusion criteria (62% males, median age 72). Hernias were most
      often indirect inguinal (40.9%) and femoral (33.5%), and 45 cases (17.5%)
      required a bowel resection. Laparoscopic repair was performed in 3 patients
      (1.2%). Synthetic mesh was placed in 70% of repairs but in only 15% of cases
      associated with a bowel resection. The medical complications rate was 16.7%; 3.6%
      had an surgical site infection, and 30-day mortality rate was 3.1%. Older age
      (odds ratio 1.05) and gross contamination (odds ratio 4.3) were independently
      associated with complications. Mesh use was not associated with surgical site
      infection (odds ratio 1.83, P = .49) or perioperative complications (odds ratio
      1.02, P = .96). With a median follow-up of 43 months, there were no mesh
      infections and recurrence rates were similar between mesh and tissue repairs
      (6.3% vs 6.8%, P = .91). CONCLUSION: Emergent groin hernia repair has high rates
      of morbidity and mortality most closely associated with increasing age and the
      presence of contamination. Although mesh use appears to be well tolerated when
      used in the absence of contamination during emergent groin hernia repair,
      recurrence rates were similar to tissue repairs.

PMID- 30217398
TI  - Enabling provider decision-making that improves quality and costs in oncology: An
      interview with Andrew Norden from Cota Healthcare.

PMID- 30217397
TI  - Postoperative pancreatic fistula: Microbial growth determines outcome.
AB  - BACKGROUND: Postoperative pancreatic fistula is a dangerous complication in
      pancreatic surgery. This study assessed the impact of microbiologic pathogens
      detected in postoperative pancreatic fistula on clinical outcomes after partial
      pancreatoduodenectomy and distal pancreatectomy. METHODS: Microorganisms in
      postoperative pancreatic fistula were identified by microbiologic analyses from
      abdominal drains or intraoperative swabs during relaparotomy. Demographic,
      operative, and microbiologic data, as well as postoperative outcomes were
      examined. RESULTS: Of 2,752 patients undergoing partial pancreatoduodenectomy and
      distal pancreatectomy, 256 patients with clinically relevant postoperative
      pancreatic fistula (International Study Group of Pancreatic Surgery [ISGPS]
      grades B and C) were identified (9.3%) and microbiologic cultures were positive
      in 210 patients (82.0%), with a higher rate after partial pancreatoduodenectomy
      (95.8%) than after distal pancreatectomy (64.3%; P < .001). Microbiologic spectra
      differed distinctively between partial pancreatoduodenectomy and distal
      pancreatectomy. Detection of microorganisms in postoperative pancreatic fistula
      resulted in a higher morbidity and mortality, including postpancreatectomy
      hemorrhage (42.4% vs 21.7%; P = .009), sepsis (38.1% vs 6.5%; P < .001), wound
      infection (30.0% vs 6.5%; P = .001), reoperation (48.1% vs 10.9%; P < .001),
      hospital stay (median 42 vs 26 days; P < .001), and overall 90-day mortality
      (19.5% vs 4.3%; P = .013) and was identified as an independent risk factor for
      sepsis, wound infection, and reoperation in the multivariate analysis.
      CONCLUSION: Detection of microorganisms in postoperative pancreatic fistula is
      frequent after pancreatic resection and indicates a turning point in the
      development of postoperative pancreatic fistula into a life-threatening
      condition. Whether early anti-infective therapy in combination with
      interventional measures or a surgical reintervention are warranted, has yet to be
      elucidated.

PMID- 30217399
TI  - Hemodynamic change and affecting factors after shoulder arthroplasty in the Asian
      population.
AB  - BACKGROUND: This retrospective study was designed to compare the hemodynamics
      among the types of shoulder arthroplasty and to evaluate predictors of
      transfusion in the Asian population. METHODS: A total of 212 shoulder
      arthroplasties (26 fracture hemiarthroplasty (fHA), 49 anatomical total shoulder
      arthroplasty (aTSA), 132 reverse total shoulder arthroplasty (rTSA), and 5
      revision surgery) from August 2004 to January 2016 were retrospectively reviewed.
      Demographics, surgical factors, and perioperative hemodynamic factors among the
      types of arthroplasty were compared. Multivariate analysis was conducted to
      determine predictors of transfusion. RESULTS: Preoperative hemoglobin and
      hematocrit levels were lower in the fracture hemiarthroplasty group (p < 0.001,
      0.001). The overall transfusion rate of shoulder arthroplasties in Asian
      population was 11.3%, and transfusion rate was significantly different among the
      types of arthroplasty (fHA 30.8%, aTSA 10.2%, rTSA 7.6%, revision 20.0%; p =
      0.010). The predictors of transfusion were preoperative hemoglobin levels <12.15
      g/dL (OR = 7.404, 95% C.I. 2.420-22.653, p < 0.001) and <10.0 g/dL at
      postoperative day 1 (OR = 5.499, 95% C.I. 1.929-15.671, p = 0.001). CONCLUSION:
      The best predictors of transfusion were hemoglobin levels of perioperative
      periods, furthermore, total amount of drainage could not represent the quantity
      of perioperative hemorrhage. Therefore, careful monitoring of hemoglobin level is
      more crucial than monitoring the amount of drainage. Hemodynamics according to
      the type of arthroplasty should be considered in shoulder arthroplasty. LEVEL OF
      EVIDENCE: Level IV, retrospective case series.

PMID- 30217400
TI  - The Hidden Cost of Commercial Antibiotic-Loaded Bone Cement: A Systematic Review
      of Clinical Results and Cost Implications Following Total Knee Arthroplasty.
AB  - BACKGROUND: The purpose of this systematic review is to compare deep prosthetic
      joint infections (PJIs) between total knee arthroplasty (TKA) patients treated
      with either antibiotic-loaded bone cement (ALBC) or plain bone cement, and to
      explore the potential cost implications of commonly used bone cement regimens. We
      hypothesized that ALBC would not substantially reduce PJIs and would thereby
      present an unnecessary cost to the healthcare system. METHODS: Using the PRISMA
      guidelines, we reviewed articles through May 2017 involving primary TKA patients
      with both ALBC cohort and plain bone cement cohort. A meta-analysis was performed
      comparing the prevalence of deep infections between cohorts. A cost comparison
      for a hypothetical setting with an annual volume of 1000 TKAs was performed to
      compare 3 commonly used cement regimens: 2 bags of ALBC used during each case, 1
      bag of ALBC with 1 bag of plain cement, and 2 bags of plain cement. Pricing at
      our institution is $215/bag for commercial ALBC and $60/bag for plain cement.
      RESULTS: Eight articles were included with a total of 34,664 patients. ALBC did
      not reduce the PJI (ALBC = 93/8189, 1.1% vs plain = 251/26,475, 0.9%; P = .09).
      The estimated costs for the 3 bone cement regimens per 1000 primary TKAs were as
      follows: 2 bags of ALBC = $430,000/y, 1 bag of ALBC +1 bag of plain cement =
      $275,000/y, and 2 bags of plain cement = $120,000/y. CONCLUSION: ALBC did not
      reduce the prevalence of PJI suggesting that ALBC may be an unnecessary cost to
      the healthcare system. Hospital systems that perform 1000 TKAs/y could save
      between $155,000 and $310,000/y by switching to plain cement.

PMID- 30217402
TI  - [ENT benign lesions and pseudo-tumors: Case no 8].

PMID- 30217401
TI  - Total Hip Arthroplasty in Young Patients in The Netherlands: Trend Analysis of
      >19,000 Primary Hip Replacements in the Dutch Arthroplasty Register.
AB  - BACKGROUND: Total hip arthroplasty (THA) is one of the most successful
      interventions in medical care. Because of shifting trends in THA and failure
      rates being higher in younger patients, we aimed to assess trends in implant
      fixation, bearing type, head diameter, and surgical approach in patients younger
      than 55 years in the Netherlands using data from the Dutch Arthroplasty Register.
      METHODS: Trends in the method of implant fixation, bearing type, head diameter,
      and surgical approach were analyzed over year of surgery (2007-2016) and over age
      groups (<25, 25-29, 30-34, 35-39, 40-44, 45-49, and 50-54 years). RESULTS:
      Between 2007 and 2016, a total of 19,915 primary THAs were performed in patients
      <55 years. Osteoarthritis was the most prevalent diagnosis (66.1%). Uncemented
      fixation was used in 79.5% of all performed THAs. The use of 32-mm head diameters
      increased (from 32.6% in 2007 to 50.1% in 2016), where an increasing trend toward
      the use of ceramic-on-polyethylene as most frequently used bearing type was
      present (from 37.5% in 2007 to 53.8% in 2016). The posterolateral surgical
      approach was the most frequently used approach; however, the anterior approach is
      used increasingly (0.1% in 2007 to 21.1% in 2016). Ceramic-on-polyethylene
      bearing surfaces, 32-mm head diameters, and the anterior approach were most
      commonly used in patients between 50 and 54 years. CONCLUSION: There was a clear
      preference for uncemented fixation in young patients. In head diameter, bearing
      type, and surgical approach, clear trends were visible. Characteristics of THA in
      young patients were subject to changing perspectives.

PMID- 30217403
TI  - ?

PMID- 30217404
TI  - [Incorporation of the gender perspective in community health. SESPAS Report
      2018].
AB  - The concepts of community health and gender perspective are often misunderstood
      or interpreted differently between different sectors and disciplines. For this
      reason, this article starts with the definition of both concepts and continues
      with a proposal for the incorporation of a gender perspective in community
      health. The gender norms determine different pathways and opportunities for
      people according to their sex, which are associated with gender inequalities in
      health and therefore must be incorporated in community health interventions. The
      gender perspective requires considering gender inequalities in power, in the
      access to and control over resources, the sexual division of labour and gender
      socialization in all phases of community health strategy implementation.
      Incorporating a gender perspective in community health is not only a matter of
      ethics and justice but also of the effectiveness of interventions.

PMID- 30217405
TI  - Factors determining parenting stress in mothers of children with atopic
      dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) influences a child's emotional and social well
      being, as well as his or her physical health. The influence of AD on the daily
      lives of parents and caregivers has also been documented. This study examined how
      parenting stress is affected by demographic background, characteristics of
      children's AD, and their family systems. METHODS: The participants were mothers
      of children, aged 2-6 years old, who had been diagnosed with AD. The predictive
      power of a model of parenting stress was examined using multiple regression
      analysis (stepwise), with parenting stress (PSI-SF) as the dependent variable,
      and children's demographics, including characteristics of AD; parents'
      demographics; QoL of families of children with AD (JCMV-CADIS); and family
      functioning (FAI) as independent variables. We handled missing values using a
      multiple imputation method. RESULTS: The pooled coefficients obtained from the
      multiple regression analysis after multiple imputation indicated that "family
      cohesion," "family system flexibility," "emotions related to social factors" and
      "occupation of mother" determined parenting stress. Lower family cohesion and
      family system flexibility predicted higher parenting stress. The high impact of
      "emotions related to social factors" on families' QoL predicted higher parenting
      stress. Full-time work by mothers predicted lower parenting stress. CONCLUSIONS:
      The current results reveal that "family cohesion," "family system flexibility,"
      "emotions related to social factors" and "full-time work by mothers" predicted
      parenting stress of mothers who had children with AD.

PMID- 30217407
TI  - Correlations between population-levels of prescription opioid dispensing and
      related deaths in Ontario (Canada), 2005-2016.
AB  - Canada is experiencing an ongoing opioid-related public health crisis, including
      persistently rising opioid (e.g., poisoning) mortality. Previous research has
      documented marked correlations between population-levels of opioid dispensing and
      deaths. We examined possible correlations between annual population-level
      dispensing of specific opioid formulations and related poisoning deaths in
      Ontario (Canada), for the period 2005-2016. Annual coroner statistics-based
      numbers of poisoning deaths associated with six main opioid formulations
      (codeine, fentanyl, hydromorphone, methadone, morphine, and oxycodone) for
      Ontario were converted into annual death rates (per 100,000 population). Annual
      dispensing data for the opioid formulations under study were based on commercial
      retail-sales data from a representative, stratified sample of community
      pharmacies (IMSQuintiles/IQVIA CompuScript), converted into Defined Daily Doses
      (DDD/1,000 population/day). Possible relationships between the annual death and
      dispensing rates were assessed by Pearson's correlation coefficient analyses.
      Death rates increased for almost all, while dispensing rates increased for half
      of the opioid categories. A significant positive correlation between death and
      dispensing rates was found for hydromorphone (r = 0.97, 95% CI: 0.88-0.99) and
      oxycodone (r = 0.90, 95% CI: 0.68-0.97) formulations; a significant negative
      correlation was found for codeine (r = -0.78, 95% CI: -0.93 to -0.37). No
      significant correlations were detected for fentanyl, methadone, and morphine
      related deaths. Strong correlations between levels of dispensing and deaths for
      select opioid formulations were found. For select others, extrinsic factors -
      e.g., increasing involvement of non-medical opioid products (e.g., fentanyl) in
      overdose deaths - likely confounded underlying correlation effects. Opioid
      dispensing levels continue to influence population-level mortality levels, and
      need to be addressed by prevention strategies.

PMID- 30217406
TI  - High-mobility group box-1 translocation and release after hypoxic ischemic brain
      injury in neonatal rats.
AB  - Inflammation contributes to neonatal brain injury. Pro-inflammatory cytokines
      represent key inflammatory meditators in neonatal hypoxic-ischemic (HI) brain
      injury. The high mobility group box-1 (HMGB1) protein is a nuclear protein with
      pro-inflammatory cytokine properties when it is translocated from the nucleus and
      released extracellularly after stroke in adult rodents. We have previously shown
      that HMGB1 is translocated from the nucleus to cytosolic compartment after
      ischemic brain injury in fetal sheep. In the current study, we utilized the Rice
      Vannucci model to investigate the time course of HMGB1 translocation and release
      after HI injury in neonatal rats. HMGB1 was located in cellular nuclei of brains
      from sham control rats. Nuclear to cytoplasmic translocation of HMGB1 was
      detected in the ipsilateral-HI hemisphere as early as zero h after HI, and
      released extracellularly as early as 6 h after HI. Immunohistochemical double
      staining detected HMGB1 translocation mainly in neurons along with release from
      apoptotic cells after HI. Serum HMGB1 increased at 3 h and decreased by 24 h
      after HI. In addition, rat brains exposed to hypoxic injury alone also exhibited
      time dependent HMGB1 translocation at 3, 12 and 48 h after hypoxia. Consequently,
      HMGB1 responds similarly after HI injury in the brains of neonatal and adult
      subjects. We conclude that HMGB1 is sensitive early indicator of neonatal HI and
      hypoxic brain injury.

PMID- 30217408
TI  - Expression profile of some neuronal and glial cell markers in the ovine ileal
      enteric nervous system during prenatal development.
AB  - The enteric nervous system (ENS) is a network of neurons and glia found in the
      gut wall and governs this gastrointestinal function independently from the
      central nervous system (CNS). ENS comprises the myenteric plexus (MP) and the
      submucous plexus (SP). In this study, we examined the expression profile of
      neurofilament heavy chain (NF-H), neuron-specific enolase (NSE), calcyclin
      (S100A6), vimentin and glial fibril acidic protein (GFAP) in ovine ileal enteric
      neurons and enteric glia cells (EGCs) during prenatal development using an
      immunohistochemical method. The material of the study consisted of 15 different
      fetal ileum tissues obtained between days 60 and 150 of pregnancy. NF-H was
      observed in the majority of ganglion cells in SP and MP throughout the fetal
      period. It was determined that there was no NF-H reaction in some ganglion cells
      in Peyer's patches of internal submucosal plexus (ISPF). In the early stage of
      pregnancy (60-90 days), there was no expression of NSE and S1006 in ileum. After
      this period, NSE and S1006 were expressed in the ganglion cells of the plexus,
      indicating an increase in the amount of expression towards the end of pregnancy.
      In the early period, vimentin expression was only detected in intramuscular
      interstitial cells (ICs) (60-90 days), but later (90-150 days) it was also seen
      in the cells around the ganglion cells in the plexus. On days 60-90 of gestation,
      GFAP expression only occurred in MP, but in later stages, staining was also
      detected in SP. In the plexus, an immunoreactivity was present in EGCs forming a
      network around the ganglion cell. During the last period of gestation (120-150
      days), the number of GFAP-positive plexus increased, with the majority of these
      stained cells being observed in MP. Interestingly, weak staining or reaction did
      not occur in ISPF, unlike other plexuses. In conclusion, this is the first study
      that demonstrated the expression of NF-H, vimentin, S100A6, NSE and glial fibril
      acidic protein (GFAP) in ovine ileal ENS in the prenatal period. In the last
      period of gestation (120-150 days), the expression profile of ENS was similar to
      that of adult animals. The expression of the used markers increased toward the
      end of pregnancy. Our results suggest that neurons and EGCs show heterogeneity,
      and GFAP and NF-H cannot be used as panenteric glial or panneuronal markers,
      respectively. We also demonstrated, for the first time, the prenatal expression
      of S100A6 in enteric neurons and the possibility of using this protein for the
      identification of enteric neurons.

PMID- 30217409
TI  - PIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for
      Targeted Granule Secretion by Cytotoxic Lymphocytes.
AB  - How cytotoxic T lymphocytes (CTLs) sense T cell receptor (TCR) signaling in order
      to specialize an area of plasma membrane for granule secretion is not understood.
      Here, we demonstrate that immune synapse formation led to rapid localized changes
      in the phosphoinositide composition of the plasma membrane, both reducing
      phosphoinositide-4-phosphate (PI(4)P), PI(4,5)P2, and PI(3,4,5)P3 and increasing
      diacylglycerol (DAG) and PI(3,4)P2 within the first 2 min of synapse formation.
      These changes reduced negative charge across the synapse, triggering the release
      of electrostatically bound PIP5 kinases that are required to replenish PI(4,5)P2.
      As PI(4,5)P2 decreased, actin was depleted from the membrane, allowing secretion.
      Forced localization of PIP5Kbeta across the synapse prevented actin depletion,
      blocking both centrosome docking and secretion. Thus, PIP5Ks act as molecular
      sensors of TCR activation, controlling actin recruitment across the synapse,
      ensuring exquisite co-ordination between TCR signaling and CTL secretion.

PMID- 30217410
TI  - Long-term outcomes of surgical treatment for intravascular leiomyomatosis.
AB  - BACKGROUND: Intravascular leiomyomatosis (IVL) is relatively rare. The optimal
      surgical method and long-term outcomes are not completely understood. METHODS:
      Medical records between 2007 and 2017 in our hospital were analyzed to identify
      IVL cases with surgical intervention. Their medical records, operative details,
      and follow-up were collected by chart review and telephone communication.
      RESULTS: Eight patients with IVL were included in the study, accounting for 0.26%
      of all uterine leiomyoma cases. Primary IVL was confined to pelvic cavity in
      three patients, extended to the inferior vena cava (IVC) below renal vein in one,
      reached IVC and right atrium in three, and reached main pulmonary artery in one.
      One-stage operation was performed for seven patients. Cardiopulmonary bypass was
      done in four patients, and aortic cross-clamp and temporary circulatory arrest
      was performed in two patients. None of the four patients with intrapulmonary
      tumors received concomitant pulmonary tumor resection. There was no operative
      mortality and four morbidities, including ureter injury (2), bladder injury (1),
      and femoral vein thrombosis (1). During follow-up, two patients exhibited local
      recurrence of the tumor in the pelvis, and one patient had rapidly growing
      intrapulmonary tumor three months post-operatively. Intrapulmonary tumors in the
      other three patients remained stationary at 6, 84, and 120 months post
      operatively. CONCLUSION: One-stage operation to completely remove IVL is feasible
      and with good long-term outcomes, which is recommended if the patient can
      tolerate the operation. Concomitant intrapulmonary tumors can be followed up
      watchfully except when associated with pleural effusion or the pathology
      indicating trend of increasing malignancy.

PMID- 30217411
TI  - Critically appraised paper: Short-term preoperative exercise training improves
      exercise capacity and reduces postoperative pulmonary complications in people
      undergoing lung cancer surgery [commentary].

PMID- 30217412
TI  - Motivational interviewing added to oncology rehabilitation did not improve
      moderate-intensity physical activity in cancer survivors: a randomised trial.
AB  - QUESTION: Does adding weekly, physiotherapist-delivered motivational interviewing
      to outpatient oncology rehabilitation for cancer survivors increase physical
      activity levels and improve physical and psychosocial outcomes that are typically
      impaired in this cohort? DESIGN: Randomised controlled trial with blinded outcome
      assessment, concealed allocation and intention-to-treat analysis. PARTICIPANTS: A
      heterogeneous sample of 46 cancer survivors (n=29 female; mean age 59 years)
      participating in a public outpatient oncology rehabilitation program.
      INTERVENTION: Participants were randomly allocated to receive oncology
      rehabilitation (n=24) or oncology rehabilitation with motivational interviewing
      delivered once weekly for 7 weeks via telephone by a physiotherapist (n=22).
      OUTCOME MEASURES: The primary outcome was amount of physical activity of at least
      moderate intensity completed in 10-minute bouts, measured by an accelerometer
      worn continuously for 1 week. Secondary outcomes included other measures of
      physical activity, sedentary behaviour, physical function, psychosocial function,
      and quality of life. RESULTS: When added to oncology rehabilitation, motivational
      interviewing caused no appreciable increase in the amount of moderate-intensity
      physical activity (MD -1.2 minutes/day, 95% CI -2.5 to 0.02). Among many
      secondary outcomes, the only statistically significant result was a small effect
      on nausea, which probably represents a Type I error. However, several secondary
      outcomes related to lower-intensity physical activity had non-significant
      confidence intervals that included large effects such as: sedentary time (SMD 
      0.67, 95% CI -1.32 to 0.02), light-intensity physical activity (SMD 0.56, 95% CI 
      0.12 to 1.21) and daily step count (SMD 0.37, 95% CI -0.30 to 1.02). CONCLUSION:
      Adding motivational interviewing to oncology rehabilitation did not increase
      moderate-intensity physical activity. Favourable trends on measures of lower
      intensity physical activity suggest that motivational interviewing should be
      further investigated for its effects on reducing sedentary time and improving
      light-intensity physical activity for cancer survivors participating in
      rehabilitation. TRIAL REGISTRATION: ANZCTR 12616001079437. [Dennett AM, Shields
      N, Peiris CL, Prendergast LA, O'Halloran PD, Parente P, Taylor NF (2018)
      Motivational interviewing added to oncology rehabilitation did not improve
      moderate-intensity physical activity in cancer survivors: a randomised trial.
      Journal of Physiotherapy 64: 255-263].

PMID- 30217413
TI  - Synthesis and biological activities of novel pyrazolomatrine derivatives.
AB  - In continuation of our program aimed at the development of new natural product
      based pesticides, a series of novel pyrazolomatrine derivatives were prepared by
      structural modifications of matrine, isolated as a quinolizidine alkaloid from
      the roots of Sophora flave. Their structures were confirmed by 1H NMR, HRMS, etc.
      Moreover, the steric structures of three compounds were determined by single
      crystal X-ray diffraction. Among all derivatives, 19-(naphthyl-2
      oyl)pyrazolomatrine (5y) showed 3.13-fold more potent acaricidal activity than
      its precusor matrine against Tetranychus cinnabarinus; 19-(4
      methylbenzoyl)pyrazolomatrine (5j) and 19-(3,5-dimethylbenzoyl)pyrazolomatrine
      (5k) displayed the promising aphicidal activity against Aphis citricola van der.
      Their structure-activity relationships were also observed.

PMID- 30217414
TI  - Discovery of DS42450411 as a potent orally active hepcidin production inhibitor:
      Design and optimization of novel 4-aminopyrimidine derivatives.
AB  - Hepcidin has emerged as the central regulatory molecule in systemic iron
      homeostasis. The inhibition of hepcidin may be a favorable strategy for the
      treatment of anemia of chronic disease. Here, we have reported the design,
      synthesis, and structure-activity relationships (SAR) of a series of 4
      aminopyrimidine compounds as inhibitors of hepcidin production. The optimization
      study of 1 led to the design of a potent and bioavailable inhibitor of hepcidin
      production, 34 (DS42450411), which showed serum hepcidin-lowering effects in a
      mouse model of interleukin-6-induced acute inflammation.

PMID- 30217415
TI  - In vitro and in vivo characterization of a novel, highly potent p53-MDM2
      inhibitor.
AB  - Small molecule inhibitors of the p53-MDM2 protein complex are under intense
      investigation in clinical trials as anti-cancer agents, including our first
      generation inhibitor NVP-CGM097. We recently described the rational design of a
      novel pyrazolopyrrolidinone core as a new lead structure and now we report on the
      synthesis and optimization of this to provide a highly potent lead compound. This
      new compound displayed excellent oral efficacy in our preclinical mechanistic in
      vivo model and marked a significant milestone towards the identification of our
      second generation clinical candidate NVP-HDM201.

PMID- 30217416
TI  - Inhibitor for FcepsilonRI expression on mast cell from Verbasucum thapsus L.
AB  - We found out 2',3'-dihydroxypuberulin from South American medicinal plant, V.
      thapsus L., as a candidate of an anti-allergic lead which inhibits the expression
      of high-affinity receptor of IgE (FcepsilonRI) on the surface of mast cells.
      Furthermore, the analysis of structure-activity relationship by using synthesized
      2',3'-dihydroxypuberulin analogs revealed that both hydroxy groups in the side
      chain and both of methyl moieties on phenolic hydroxy groups were crucial for
      potent activity, but absolute configuration of C-3' position wasn't. The active
      principle, 2',3'-dihydroxypuberulin, was disclosed to down-regulate the mRNA
      level of beta-chain of FcepsilonRI, different from previous reported active
      natural product reducing gamma-chain level.

PMID- 30217417
TI  - Managing Medicines for Patients Dying at Home: A Review of Family Caregivers'
      Experiences.
AB  - CONTEXT: Increased life expectancy, technical advances in treatment and symptom
      control, and the extension of palliative care in community settings not only
      lengthen life but also make it possible for many patients to be cared for, and to
      die, at home. Moreover, death increasingly occurs in late old age and after a
      prolonged period of comorbidity and/or frailty. This has far-reaching
      consequences for the way that professional services are resourced and organized
      and for the informal carers who are often responsible for providing the greater
      part of patient care, including management of complex medication regimes.
      OBJECTIVES: To explore the literature focused on family caregivers' (FCGs)
      experiences of medication management for patients being cared for and dying at
      home. METHODS: This literature review takes a critical interpretive synthesis
      approach to the review of 15 identified articles. RESULTS: Findings show that
      FCGs can struggle to manage medications for someone who is dying at home, yet
      there is an expectation that they will take on these roles and are often judged
      by professional standards. Five key themes identified particular issues around
      administration, organizational skills, empowerment, relationships, and support.
      CONCLUSION: As increasing demands are placed on FCGs, there remains limited
      acknowledgment or understanding of the challenges they face, how they cope, or
      could be best supported. Alongside training, FCGs need access to 24 hours of
      support and medication reviews to rationalize unnecessary medications.
      Furthermore, the ethical challenges arising from administering medicines at the
      end of life also need to be acknowledged and discussed.

PMID- 30217418
TI  - The hidden side of oral thrombin inhibitors.

PMID- 30217419
TI  - Seasonal and circadian patterns of myocardial infarction by coronary artery
      disease status and sex in the ACTION Registry-GWTG.
AB  - BACKGROUND: Myocardial infarction (MI) presentations are more common during
      winter months and morning hours. However, it is unknown whether MI with
      obstructive coronary artery disease (MI-CAD) and non-obstructive CAD (MINOCA)
      display similar patterns. METHODS: We evaluated seasonal and circadian patterns
      of MI presentation by coronary artery disease (CAD) status and sex in patients
      with MI from 2007 to 2014 in the National Cardiovascular Data Registry (NCDR)
      Acute Coronary Treatment Intervention Outcomes Network (ACTION) Registry-Get With
      the Guidelines. Adult patients who underwent coronary angiography for MI were
      included. Patients with missing age, sex, or angiographic data, cocaine use,
      thrombolytic therapy prior to catheterization, or prior revascularization were
      excluded. Baseline demographics and characteristics of symptom onset, including
      season and time of day of presentation, were compared by CAD status and sex.
      RESULTS: Among 322,523 patients, 112,547 were female (35%); 18,918 had MINOCA
      (5.9%). There was no seasonal pattern of MI overall. However, both men and women
      with MINOCA presented more often in the summer and fall while MI-CAD
      presentations were equally distributed across seasons. The most common time of
      presentation was 8 am-2 pm regardless of CAD status or sex. A secondary peak in
      women with MINOCA during late afternoon hours was also identified. CONCLUSIONS:
      Seasonal variation of MI differed between MINOCA and MI-CAD, with a small
      increase in MINOCA incidence in the summer and fall. MINOCA and MI-CAD most
      commonly occurred in the morning, with a secondary peak in late afternoon in
      women with MINOCA. These differences in presentation may relate to underlying MI
      pathophysiology.

PMID- 30217420
TI  - Risk stratification in acute coronary syndromes: The grace to move beyond the
      GRACE.

PMID- 30217421
TI  - The stricter criteria for Class I CRT indication suggested by the 2016 ESC
      Guidelines reliably exclude patients with a worse prognosis in comparison with
      the 2013 ESC indication criteria.
AB  - BACKGROUND: The European Society of Cardiology (ESC) Guidelines published in 2016
      modified indications for cardiac resynchronization therapy (CRT) in comparison
      with the 2013 ESC Guidelines. The aim of this analysis was to evaluate the impact
      of the stricter criteria suggested by the 2016 ESC Guidelines on patient outcome
      in a real-world population. METHODS: We collected data on 930 consecutive
      patients with complete outcome information who had undergone CRT implantation
      from 2011 to 2013 from the CRT-MORE registry. Patients were classified according
      to 2013 (Reference) and 2016 (Current) ESC Guidelines. The primary end-point of
      the study was death from any cause and heart failure hospitalization. RESULTS:
      According to the Reference Guidelines, 650 (69.9%) patients met Class I
      indications, 190 (20.4%) Class IIa, 39 (4.2%) Class IIb and 51 (5.5%) Class III.
      According to the Current Guidelines, 563 (60.5%) patients met Class I
      indications, 145 (15.6%) Class IIa, 108 (11.6%) Class IIb and 114 (12.3%) Class
      III. On comparing the Reference and Current Guidelines, the 538 patients who
      confirmed their Class I indication had a better outcome in terms of freedom from
      the combined end-point of heart failure (HF) hospitalization or death from any
      cause (hazard ratio (HR) of 0.64; 95% CI 0.42 to 0.99; p = 0.0436) when compared
      to the 112 patients who lost their class I indication (84 moved to class IIb and
      28 moved to class III). CONCLUSIONS: The stricter criteria for Class I CRT
      indication suggested by the 2016 ESC Guidelines excluded about 20% of patients
      with a worse prognosis. CLINICAL TRIAL REGISTRATION: CRT MORE: Cardiac
      Resynchronization Therapy Modular Registry URL:
      http://clinicaltrials.gov/Identifier:NCT01573091.

PMID- 30217422
TI  - Patient-specific in vivo right ventricle material parameter estimation for
      patients with tetralogy of Fallot using MRI-based models with different zero-load
      diastole and systole morphologies.
AB  - Patient-specific in vivo ventricle material parameter determination is important
      for cardiovascular investigations. A new cardiac magnetic image (CMR)-based
      modeling approach with different zero-load diastole and systole geometries was
      adopted to estimate right ventricle material parameter values for healthy and
      patients with Tetralogy of Fallot (TOF) and seeking potential clinical
      applications. CMR data were obtained from 6 healthy volunteers and 16 TOF
      patients with consent obtained. CMR-based RV/LV models were constructed using two
      zero-load geometries (diastole and systole, 2G model). Material parameter values
      for begin-filling (BF), end-filling (EF), begin-ejection (BE), and end-ejection
      (EE) were recorded for analyses. Effective Young's moduli (YM) for fiber
      direction stress-strain curves were calculated for easy comparisons. The mean EE
      YM value of TOF patients was 78.6% higher than that of the healthy group (HG).
      The mean end-ejection YM value from worse-outcome TOF group (WG) post pulmonary
      valve replacement (PVR) surgery was 59.5% higher than that from the better
      outcome TOF group (BG). Using begin-filling YM and end-ejection YM as predictors
      and the classic logistic regression model to different better-outcome group
      patients from worse-outcome group patients, the areas under Receiver Operating
      Characteristic (ROC) curves were found to be 0.797 and 0.883 for begin-filling YM
      and end-ejection YM, respectively. The sensitivity and specificity 0.761 and
      0.755 using end-ejection YM as the predictor. This preliminary study suggests
      that ventricle material stiffness could be a potential parameter to be used to
      differentiate BG patients from WG patients with further effort and large-scale
      patient data validations.

PMID- 30217423
TI  - Mechanisms underlying the J-curve for diastolic blood pressure: Subclinical
      myocardial injury and immune activation.
AB  - BACKGROUND: Low diastolic blood pressure (DBP) is associated with increased risk
      of cardiovascular events. In patients with coronary artery disease (CAD),
      limitations in coronary blood flow and immune activity are implicated mechanisms,
      but evidence is lacking. We investigated the association between DBP, biomarkers
      of myocardial injury, inflammation, immune activation and incident events in
      patients with CAD. METHODS: We studied 2448 adults (mean age 65 +/- 12 years, 68%
      male, median follow-up 4.5 years) with CAD. DBP was categorized into 10 mm Hg
      increments. Biomarkers of myocardial injury (high sensitivity cardiac troponin-I
      [hs-cTnI]) and immune activity/inflammation (soluble urokinase plasminogen
      activator receptor [suPAR]) were dichotomized at their median values. DBP 70-79
      mm Hg was used as the referent group, and individuals were followed prospectively
      for adverse outcomes. RESULTS: After adjusting for demographic and clinical
      covariates, individuals with DBP < 60 mm Hg had increased odds of elevated levels
      of hs-cTnI (OR = 1.68; 95% CI = 1.07, 2.65) and suPAR (OR = 1.71; 95% CI = 1.10,
      2.65) compared to the referent group. Additionally, DBP < 60 mm Hg was associated
      with increased adjusted risk of cardiovascular death or MI (HR = 2.04; 95% CI =
      1.32, 3.16) and all-cause mortality (HR = 2.41; 95% CI = 1.69, 3.45). CONCLUSION:
      In patients with CAD, DBP < 60 mm Hg is associated with subclinical myocardial
      injury, immune/inflammatory dysregulation and incident events. Aggressive BP
      control may be harmful in these patients, and further investigation is warranted
      to determine appropriate BP targets in patients with CAD.

PMID- 30217424
TI  - Correlation between CD4+CD28null T lymphocytes, regulatory T cells and plaque
      rupture: An Optical Coherence Tomography study in Acute Coronary Syndromes.
AB  - BACKGROUND: A sizeable proportion of patients with Acute Coronary Syndromes (ACS)
      shows a unique adaptive immune system profile, associated to a worse outcome,
      characterized by higher CD4+CD28null T-cells, lower regulatory T-cells (Treg) and
      increased CD4+CD28null/Treg ratio. We sought to investigate the correlation
      between CD4+CD28null T-cells, Treg, CD4+CD28null/Treg ratio and plaque phenotype
      as assessed by Optical Coherence Tomography (OCT). METHODS: Peripheral blood
      mononuclear cells (PBMC) were collected from 30 Non-ST Elevation Myocardial
      Infarction (NSTEMI) patients, sub-grouped according to OCT analysis of culprit
      lesions into two cohorts: Ruptured Fibrous Cap (NSTEMI-RFC, n = 12) and Intact
      Fibrous Cap (NSTEMI-IFC, n = 18). Stable Angina patients (SA, n = 18) were used
      as controls. We examined the frequency of CD4+CD28null and Treg (defined as
      CD4+CD25highCD127lowFoxp3+ T-cells) by flow-cytometry. RESULTS: CD4+CD28null
      frequency (median, range) was significantly higher in NSTEMI-RFC patients (17.3%,
      12.5-33.8) as compared with NSTEMI-IFC (3.8%, 0.3-14.1) and SA (3%, 0.6-17.7) (P
      < 0.001 for all comparisons). We also found a higher CD4+CD28null/Treg ratio in
      NSTEMI-RFC patients (6.6%, 3.7-13.9) than in NSTEMI-IFC (1.6%, 0.3-5.2) and SA
      (1.2%, 0.3-8.7) (P < 0.001 for all comparisons). Finally, there was an inverse
      correlation between CD4+CD28null/Treg ratio and cap-thickness (R = -0.44; P =
      0.002). CONCLUSION: Patients with NSTEMI presenting with RFC as culprit lesion at
      OCT evaluation have a specific perturbation of adaptive immunity, mostly
      involving CD4+CD28null T- cells and Tregs, as compared with patients with IFC and
      SA. This specific imbalance of T-cells might play a key role in fibrous cap
      thinning, predisposing atherosclerotic plaque to rupture.

PMID- 30217425
TI  - Changes in fat mass and fat-free-mass are associated with incident hypertension
      in four population-based studies from Germany.
AB  - BACKGROUND: We estimated the association of changes in body weight, waist
      circumference (WC), fat mass (FM) and fat-free mass (FFM) with changes in blood
      pressure and incident hypertension using data from four German population-based
      studies. METHODS: We analyzed data from 4467 participants, aged 21 to 82 years
      not taking antihypertensive medication and not having type 2 diabetes mellitus or
      a history of myocardial infarction at baseline and follow-up, from four
      population-based studies conducted in Germany. Body weight, WC, and blood
      pressure were measured at baseline and follow-up (median follow-up of the single
      studies 4 to 7 years). FM and FFM were calculated based on height-weight models
      derived from bioelectrical impedance studies. Hypertension was defined as
      systolic blood pressure >= 140 mmHg or diastolic blood pressure >= 90 mmHg.
      Confounder-adjusted linear and logistic regressions were used to associate
      changes in anthropometric markers with changes in blood pressure, incident
      hypertension, and incident normalization of blood pressure. RESULTS: In a pooled
      dataset including all four studies, increments in body weight, WC, FM, and FFM
      were statistically significantly associated with incident hypertension and
      changes in systolic and diastolic blood pressure over time. Decreases in body
      weight, FM, and FFM were significantly associated with incident normalization of
      blood pressure. CONCLUSIONS: Our data suggests that the well-established
      association between obesity and blood pressure levels might be more related to
      body composition rather than to total body weight per se. Our findings indicate
      that gaining or losing FFM has substantial impact on the development or reversion
      of hypertension.

PMID- 30217426
TI  - Paving the way for improving no-reflow phenomenon.

PMID- 30217427
TI  - Copeptin as a prognostic biomarker in acute myocardial infarction.
AB  - BACKGROUND: Copeptin - the C-terminal section of vasopressin precursor - is a
      novel biomarker, that has been shown to be a useful prognostic factor in heart
      failure, ischemic stroke and in acute myocardial infarction (MI) but with
      restricted population and follow-up in ST-segment elevation MI (STEMI) setting.
      We evaluated in this study the hypothesis that copeptin measured on admission is
      an independent predictor of one-year all-cause mortality after a STEMI. METHODS:
      Copeptin was measured immediately on arrival in the catheterization laboratory in
      a cohort of unselected STEMI patients and was compared to the peak of cardiac
      troponin I as a prognosis marker. One-year follow-up was performed. RESULTS: We
      included 401 STEMI patients (77% of men, mean age 64 +/- 14 years) treated by
      primary percutaneous coronary intervention. Copeptin on admission was
      significantly higher in patients who died during the one-year follow-up than in
      survivors (154.8 pmol/L; IQR [63.9-304.8] vs 30.3 pmol/L; IQR [10.8-93.5]); p <
      0.0001). There was an increase in mortality at one year from the lowest to the
      highest quartile of copeptin. After Cox regression analysis, copeptin was an
      independent predictor of death at one year (adjHR 3.1, 95% CI [1.5-6.2], p =
      0.001). When compared to the peak value of cardiac troponin I, copeptin measured
      on admission had a better prognostic value to predict one-year mortality (AUC of
      0.74 vs 0.60, p = 0.022). CONCLUSION: Copeptin measured on admission is a
      reliable and independent prognostic biomarker of one-year mortality in acute
      myocardial infarction patients.

PMID- 30217428
TI  - Optimizing flecainide plasma concentration profile for atrial fibrillation
      conversion while minimizing adverse ventricular effects by rapid, low-dose
      intratracheal or intravenous administration.
AB  - BACKGROUND: We investigated whether rapid administration of a low dose of
      flecainide, either intratracheally or intravenously (IV), could accelerate
      conversion of atrial fibrillation (AF) while reducing adverse ventricular
      effects. METHODS: Flecainide was delivered via intratracheal administration at
      1.5 mg/kg bolus and compared to IV infusion at 1.0 mg/kg over 2 min (lower-dose,
      rapid) and 2.0 mg/kg over 10 min (ESC guideline) in closed-chest, anesthetized
      Yorkshire pigs. Catheters were fluoroscopically positioned in right atrium to
      measure atrial depolarization (Pa) duration and left ventricle (LV) to measure
      QRS complex duration and contractility (LV dP/dt) during atrial pacing at 140
      beats/min. Flecainide was delivered intratracheally via a catheter positioned at
      the bifurcation of the main bronchi. AF was induced by intrapericardial
      administration of acetylcholine followed by burst pacing. RESULTS: Flecainide
      reduced AF duration similarly by intratracheal and IV delivery. Peak plasma
      levels were comparable but Tmax differed and coincided with peaks in Pa
      prolongation. The area under the curve indicating sustained plasma levels was
      greater for higher-dose, slow IV flecainide than for either intratracheal
      instillation (by 32%) or lower-dose, rapid IV infusion (by 88%). As a result,
      higher-dose, slow IV flecainide caused 58% (p < 0.03) and 48% (p < 0.006) greater
      increases in QRS complex duration and 61% and 96% (both, p < 0.02) greater
      reductions in contractility compared to intratracheal and lower-dose, rapid IV
      flecainide, respectively. CONCLUSION: Lower-dose, rapid flecainide, delivered
      either intratracheally or IV, optimizes the plasma concentration profile for
      effective conversion of AF while minimizing adverse effects on QRS complex
      duration and LV contractility.

PMID- 30217429
TI  - Gastric band tubing causing cecal volvulus.

PMID- 30217430
TI  - [Pyelo-ureteral anastomosis, for stenosis of the kidney transplant ureter, by
      laparoscopic approach with robotic assistance].

PMID- 30217431
TI  - Inferring postimplant dose distribution of salvage permanent prostate implant
      (PPI) after primary PPI on CT images.
AB  - PURPOSE: To evaluate the dose distribution of additional radioactive seeds
      implanted during salvage permanent prostate implant (sPPI) after a primary
      permanent prostate implant (pPPI). METHODS AND MATERIALS: Patients with localized
      prostate cancer were primarily implanted with iodine-125 seeds and had a
      dosimetric assessment based on day 30 postimplant CT (CT1). After an average of 6
      years, these patients underwent sPPI followed by the same CT-based evaluation of
      dosimetry (CT2). Radioactive seeds on each CT were detected. The detected primary
      seeds on CT1 and CT2 were registered and then removed from CT2 referred as a
      modified CT2 (mCT2). Dosimetry evaluations (D90 and V100) of sPPI were performed
      with dedicated planning software on CT2 and mCT2. Indeed, prostate volume, D90,
      and V100 differences between CT2 and either CT1 or mCT2 were calculated, and
      values were expressed as mean (standard deviation). RESULTS: The mean prostate
      volume difference between sPPI and pPPI over the 6 patients was 9.85 (7.32) cm3.
      The average D90 and V100 assessed on CT2 were 486.5 Gy (58.9) and 100.0% (0.0),
      respectively, whereas it was 161.3 Gy (47.5) and 77.3% (25.2) on mCT2 (p = 0.031
      each time). The average D90 the day of sPPI [145.4 Gy (11.2)] was not
      significantly different from that observed on mCT2 (p = 0.56). CONCLUSION:
      Postimplant D90 and V100 of sPPI after pPPI can be estimated on CT images after
      removing the primary seeds.

PMID- 30217432
TI  - Phase II study of intraoperative dosimetry for prostate brachytherapy using
      registered ultrasound and fluoroscopy.
AB  - PURPOSE: To assess the performance of a system of intraoperative dosimetry and
      obtain estimates of dosimetry outcomes achieved when utilizing the system in a
      Phase II clinical trial. METHODS AND MATERIALS: Forty-five patients undergoing
      permanent Pd-103 seed implantation for prostate cancer were prospectively
      enrolled. Seed implantation was performed and dose was tracked intraoperatively
      using intraoperative registered ultrasound and fluoroscopy (iRUF). Three
      dimensional seed locations were computed from X-rays and registered to ultrasound
      for intraoperative dosimetry, followed by adaptive plan modification to achieve
      prostate V100 >=95% and >=95% D90. Time required for iRUF was recorded.
      Postoperative CT/MRI scans were performed 1 day after the implantation and used
      as reference for dosimetric analysis. Dosimetric parameters for the prostate and
      urethra were compared between standard ultrasound-based dosimetry (USD), iRUF,
      and postoperative CT/MRI. RESULTS: Mean total time for iRUF was <30 min. A mean
      of four seeds (0-12) were added per implant to correct cold spots discovered by
      iRUF. Day 1 CT/MRI prostate V100 was >=95% for 44/45 patients; 1 patient had Day
      1 V100 93%. No patient had rectal V100 exceeding 1 cc. Compared to CT/MRI, iRUF
      dosimetry had significantly smaller mean differences and higher correlations for
      all prostate and urethral dosimetric parameters examined than USD. Both USD and
      iRUF tended to overestimate dose, but with less bias in iRUF than USD.
      CONCLUSIONS: Intraoperative dosimetry utilizing iRUF was associated with
      acceptable increase in procedure time and enabled very high rates of achieving
      excellent prostate dose coverage. iRUF intraoperative dosimetry approximated
      postoperative CT/MRI dosimetry to a greater degree than USD for the prostate and
      urethra.

PMID- 30217433
TI  - Evaluation of effective treatment depth in skin cancer treatments with electronic
      brachytherapy.
AB  - PURPOSE: To evaluate changes in the percent depth dose (PDD) and effective depth
      of treatment due to force applied by the applicator during treatments of
      nonmelanoma skin cancer with the Xoft electronic brachytherapy system. METHODS:
      To simulate compressible tissue, a 5-mm tissue-equivalent bolus was used. A soft
      x-ray ion chamber was used for output measurements, which were performed for all
      Xoft surface applicators with plastic endcaps in place. Output was first measured
      at 5 mm depth with minimal pressure from the applicator on the bolus and then
      repeated after applying uniform pressure on the applicator to calculate the
      change in PDD and effective treatment depth. RESULTS: For the 10-mm cone, a
      moderate force of 5 N changed the PDD by more than 20%. The effect was also
      pronounced for the 20-mm cone, while minimal for the 35- and 50-mm cones. Even
      when only a moderate force was applied, the effective prescription depth changed
      by several millimeters, on the order of a typical prescription depth. CONCLUSION:
      Based on the results of this simulation, excessive pressure applied on the skin
      by the applicator can drastically alter the PDD and effective treatment depth.
      The effect is most pronounced for the 10- and 20-mm cones, which tend to be used
      most frequently. Inappropriate applicator placement may therefore result in
      significant consequences such as excessive dose to the target, severe skin
      reaction, permanent discoloration, skin indentation, and poor overall cosmesis
      upon completion of treatment.

PMID- 30217434
TI  - Declining brachytherapy utilization for high-risk prostate cancer-Can clinical
      pathways reverse the trend?
AB  - PURPOSE: Although external beam radiation therapy (EBRT) plus a brachytherapy
      boost (BB) offers a 20% improvement in biochemical progression-free survival
      compared with dose-escalated EBRT alone for men with intermediate and high-risk
      prostate cancer, population studies show a concerning decline in BB utilization.
      METHODS: We modified our clinical pathway (CP) in January 2016 to indicate EBRT
      with BB as first-choice modality for high-risk prostate cancer, based on
      preliminary findings of Androgen Suppression Combined with Elective Nodal and
      Dose-Escalated Radiation Therapy. A retrospective review was performed on 659
      patients with high-risk prostate cancer treated with definitive intent EBRT +/-
      BB within a network of 19 sites between December 2011 and July 2017. chi2 test
      was used to determine changes in practice pattern before vs. after CP
      modification. RESULTS: Before CP modification, 25.2% of patients were planned for
      BB, compared with 45.4% afterward (p < 0.001). Among 23 nonbrachytherapist
      physicians, utilization of BB increased from 3.4% to 14.8% (p < 0.001) after CP
      modification. Among nine brachytherapists, utilization increased from 46.4% to
      55.6% (p = 0.120). Among patients treated by a nonbrachytherapist who did not
      receive BB, the reason was physician preference in 59.7%, patient preference in
      19.9%, and other in 20.4%. CONCLUSION: Based on recent evidence suggesting
      improved biochemical progression-free survival with use of BB for high-risk
      prostate cancer, we modified our CP, after which we observed increased use of a
      BB across a network, especially among physicians who do not perform
      brachytherapy. However, physician preference remains the most significant factor
      in the nonutilization of BB. New mechanisms are needed to overcome this barrier.

PMID- 30217436
TI  - Corrigendum to 'A theoretical computerized study for the electrical conductivity
      of arterial pulsatile blood flow by an elastic tube model' [Medical Engineering &
      Physics, 38 (2016) 1439-1448].

PMID- 30217437
TI  - Human papillomavirus in tonsillectomy specimen from China and Pakistan -
      Prevalence and genotype distribution.
AB  - BACKGROUND: The expected corresponding increase in tonsillar human papillomavirus
      (HPV) infection associated with increasing incidence of oropharyngeal squamous
      cell carcinoma (OPSCC) substantiate the evaluation of normal tonsillar tissue in
      different population. The epidemiology of HPV in tonsillar tissue varies
      geographically. This study evaluated samples from two countries to determine the
      prevalence in respective samples. OBJECTIVE: To characterize HPV infection in non
      malignant tonsillar tissue from Shaanxi, China (herein after referred to as
      China) and Punjab, Pakistan (herein after referred to as Pakistan). METHODOLOGY:
      The DNA extracted from formalin-fixed, paraffin-embedded tumor free tonsillar
      tissue was evaluated using polymerase chain reaction (PCR). A total of 367 cases
      from China and 139 cases from Pakistan were screened for HPV DNA using GP5+/GP6+
      consensus primer. Genotype of the positive cases was determined for common HPV
      types (6, 11, 16, 18, 52, 58) simultaneously by type-specific PCR. RESULTS: The
      mean age of cohorts in China was 13.42 (Median age 7, Range 2-72 years) while in
      Pakistan it was 10.77 (Median age 8, Range 3-42 years) the gender distribution
      was 61.6% male in China and in Pakistan they were 56.8%, rest were females. The
      overall prevalence of HPV in China was 2.45% and 2.16% in Pakistan. High risk
      human papillomavirus was 1.63% in China with 5 cases positive for HPV 16 and HPV
      58 in 1 case. In Pakistan, 2 cases (1.43%) of HPV 16 were detected. Low-risk
      types include HPV 11 present in 2 cases from China, while HPV 6 was detected in 1
      case each from both the countries. CONCLUSION: A low prevalence of HPV was found
      in China and Pakistan; high-risk and low-risk HPV were detectable in tonsillar
      tissue from both countries. Age stratification (< 5 years, 5-14 years, 15-25
      years, > 25 years) suggest that sexual and non-sexual transmission of the virus
      can occur. The difference in the genotype distribution geographically within
      China and with Pakistan was observed in the case of HPV 58. The most common type
      in both the countries was HPV 16.

PMID- 30217438
TI  - Real-life evaluation of the clinical, functional, and hematological effects of
      mepolizumab in patients with severe eosinophilic asthma: Results of a single
      centre observational study.
AB  - Mepolizumab is a humanized monoclonal antibody which targets interleukin-5 (IL-5)
      and is nowadays available in many countries for add-on biological therapy of
      severe eosinophilic asthma. Although the approval of mepolizumab use in clinical
      practice has been made possible by several successful pre-marketing controlled
      trials, so far only a very few studies have been performed in a real-life
      setting. Within such a context, our present observational investigation refers to
      14 patients with refractory eosinophilic asthma, currently treated with
      mepolizumab at the Respiratory Unit of "Magna Graecia" University Hospital
      located in Catanzaro, Italy, whose anti-IL-5 treatment began between June 2017
      and January 2018. These patients experienced a significant increase in asthma
      control test (ACT) score, that was evaluated at baseline (13.64 +/- 3.00), as
      well as after 4 weeks (18.86 +/- 3.15; p < 0.0001) and 24 weeks (20.07 +/- 1.94;
      p < 0.0001) of add-on therapy with mepolizumab. This relevant improvement in
      symptom control was paralleled by a dramatic fall of blood eosinophil numbers,
      counted at baseline (647.1 +/- 274.7 cells/MUl), and at the 4th (147.8 +/- 66.5
      cells/MUl; p < 0.0001) and 24th week (98.6 +/- 40.3 cells/MUl; p < 0.0001) after
      starting add-on treatment with mepolizumab. These changes were associated with
      significant and stable increases in FEV1, which was recorded at baseline (1389 +/
      454.3 mL), as well as after 4 weeks (1711 +/- 482.3 mL; p < 0.001) and 24 weeks
      (1701 +/- 456.0 mL; p < 0.01). Moreover, in comparison to the 6 months preceding
      the beginning of treatment with mepolizumab, after 24 weeks of anti-IL-5 therapy
      significant decreases were detected with regard to exacerbation numbers (from
      3.64 +/- 1.86 to 1.0 +/- 0.78; p < 0.001) and oral intake of prednisone (from
      24.11 +/- 10.36 mg/day to 1.78 +/- 3.82 mg/day). Therefore, these preliminary
      data referring to our single-centre observational study corroborate, in a real
      life environment, the efficacy of mepolizumab for treatment of patients with
      exacerbation-prone, corticosteroid-refractory, severe eosinophilic asthma.

PMID- 30217439
TI  - Dopaminergic neurons are preferentially responsive to advertisement calls and co
      active with social behavior network nuclei in sneaker male midshipman fish.
AB  - Vocal species use acoustic signals to facilitate diverse behaviors such as mate
      attraction and territorial defense. However, little is known regarding the neural
      substrates that interpret such divergent conspecific signals. Using the plainfin
      midshipman fish model, we tested whether specific catecholaminergic (i.e.,
      dopaminergic and noradrenergic) nuclei and nodes of the social behavior network
      (SBN) are differentially responsive following exposure to playbacks of divergent
      social signals in sneaker males. We chose sneaker (type II) males since they
      attempt to steal fertilizations from territorial type I males who use an
      advertisement call (hum) to attract females yet are also subjected to vocal
      agonistic behavior (grunts) by type I males. We demonstrate that induction of
      cFos (an immediate early gene product and proxy for neural activation) in two
      forebrain dopaminergic nuclei is greater in sneaker males exposed to hums but not
      grunts compared to ambient noise, suggesting hums preferentially activate these
      nuclei, further asserting dopamine as an important regulator of social-acoustic
      behaviors. Moreover, acoustic exposure to social signals with divergent salience
      engendered contrasting shifts in functional connectivity between dopaminergic
      nuclei and nodes of the SBN, supporting the idea that interactions between these
      two circuits may underlie adaptive decision-making related to intraspecific male
      competition.

PMID- 30217440
TI  - An analysis of the cosmetic surgery experience acquired through UK plastic
      surgery training.
AB  - AIMS: Cosmetic surgery is an essential component of Plastic Surgery training. Our
      study demonstrates the average cosmetic surgery experience of UK Plastic Surgery
      registrars over their 6-year training scheme. Comparison is made with the
      operative requirements for the Certificate of Completion of Training (CCT) and
      the Royal College of Surgeons (RCS) Cosmetic Certification scheme. METHODS: By
      using the web-based eLogbook, we analysed all the cosmetic surgery operations
      recorded by Plastic Surgery registrars during their specialist training. The
      weighted mean average number of procedures was calculated for different areas of
      cosmetic surgery practice, according to the level of supervision. The number of
      RCS cosmetic credits acquired for eight domains of cosmetic surgery was
      calculated, thus enabling comparison with the operative requirements for
      certification. RESULTS: eLogbook data were collated for 454 registrars from 2010
      to 2016 inclusive. Trainees participated in a mean of 122 cosmetic operations
      during their training (50% as an assistant), which satisfies the requirement of
      100 procedures for CCT. The majority of trainee involvement (66%) was with
      cosmetic breast and body contouring cases. Comparison with the criteria for
      cosmetic certification reveals that on average, trainees could certify in
      cosmetic breast and body contouring surgery but would be unable to accredit in
      other areas of practice. CONCLUSIONS: Current UK training affords sufficient
      cosmetic surgery exposure for CCT but offers a limited breadth of exposure.
      Trainees who wish to certify in cosmetic surgery of the head and neck region will
      likely be required to seek additional experience outside their deanery training
      programme.

PMID- 30217435
TI  - CRF modulation of central monoaminergic function: Implications for sex
      differences in alcohol drinking and anxiety.
AB  - Decades of research have described the importance of corticotropin-releasing
      factor (CRF) signaling in alcohol addiction, as well as in commonly co-expressed
      neuropsychiatric diseases, including anxiety and mood disorders. However, CRF
      signaling can also acutely regulate binge alcohol consumption, anxiety, and
      affect in non-dependent animals, possibly via modulation of central monoaminergic
      signaling. We hypothesize that basal CRF tone is particularly high in animals and
      humans with an inherent propensity for high anxiety and alcohol consumption, and
      thus these individuals are at increased risk for the development of alcohol use
      disorder and comorbid neuropsychiatric diseases. The current review focuses on
      extrahypothalamic CRF circuits, particularly those stemming from the bed nucleus
      of the stria terminalis (BNST), found to play a role in basal phenotypes, and
      examines whether the intrinsic hyperactivity of these circuits is sufficient to
      escalate the expression of these behaviors and steepen the trajectory of
      development of disease states. We focus our efforts on describing CRF modulation
      of biogenic amine neuron populations that have widespread projections to the
      forebrain to modulate behaviors, including alcohol and drug intake, stress
      reactivity, and anxiety. Further, we review the known sex differences and
      estradiol modulation of these neuron populations and CRF signaling at their
      synapses to address the question of whether females are more susceptible to the
      development of comorbid addiction and stress-related neuropsychiatric diseases
      because of hyperactive extrahypothalamic CRF circuits compared to males.

PMID- 30217441
TI  - Re: Wound outcomes in negative pressure dressings (WOUND) study - A randomised
      trial in lower limb skin cancer grafts.

PMID- 30217442
TI  - BCR-ABL tyrosine kinase inhibition induces metabolic vulnerability by preventing
      the integrated stress response in K562 cells.
AB  - The integrated stress response (ISR) is a cellular process that is characterized
      by activation of eukaryotic initiation factor (eIF)2alpha kinases and subsequent
      induction of activating transcription factor (ATF)4. The ISR plays an important
      role in protecting cells from tumor-related metabolic stresses, such as nutrient
      deprivation and perturbed proteostasis. Here, we showed that disruption of the
      ISR, together with increased cellular stress vulnerability, was produced by
      pharmacological inhibition of BCR-ABL, the oncogenic driver in chronic myeloid
      leukemia (CML). Treatment of CML-derived K562 cells with BCR-ABL tyrosine kinase
      inhibitors, including imatinib, dasatinib, nilotinib and ponatinib, prevented
      activation of eIF2alpha kinases, protein kinase-like endoplasmic reticulum kinase
      (PERK) and general control nonderepressible 2, and downstream ATF4 induction
      during metabolic stress. Prevention of ATF4 induction likely occurred as a result
      of the combinatorial suppression of the eIF2alpha kinase and phosphoinositide 3
      kinase/mammalian target of rapamycin signaling pathways. In addition, we found
      that pharmacological inhibition of PERK mimicked BCR-ABL inhibition to enhance
      apoptosis induction under stress conditions. These findings indicate that the ISR
      is under the control of BCR-ABL and may foster adaptation to tumorigenic stresses
      in CML cells.

PMID- 30217443
TI  - SPECT/CT imaging of HER2 expression in colon cancer-bearing nude mice using 125I
      Herceptin.
AB  - An accurate assessment of HER2 status in patients with colorectal cancer is very
      important, because only the patients overexpressing HER2 can benefit most from
      the anti-HER2 targeted therapy. In this study, we investigated the feasibility of
      detecting HER2 expression in colon cancer by SPECT imaging using 125I-Herceptin,
      which showed high labeling rate, good in vitro stability and high binding
      specificity for HER2. HER2-positive mouse colon adenocarcinoma cell line (MC 38)
      was chosen as the colon caner cell model, and used for the establishment of colon
      cancer-bearing nude mice model. SPECT/CT imaging suggested that the tumors can be
      visualized at 12 h after the injection of 125I-Herceptin, and the uptake of
      tracer in tumors reached the peak at 24 h after injection, and can be attenuated
      significantly by pretreatment with an excess of nonlabeled Herceptin. These
      results indicates that 125I-Herceptin can be considered as an effective SPECT
      probe for the non-invasive detection of HER2 expression in colon cancer.

PMID- 30217444
TI  - ALDH2 mediates the dose-response protection of chronic ethanol against
      endothelial senescence through SIRT1/p53 pathway.
AB  - Aldehyde dehydrogenase 2 (ALDH2) plays essential roles in drinking-associated
      diseases or effects. As we have previously reported, ALDH2 mediates acute ethanol
      induced eNOS activation in vitro. However, whether chronic ethanol treatment has
      a dose-response endothelial protection, as well as the possible mediating role of
      ALDH2 involved, is unclear. Here, we show that appropriate dose of ethanol
      preserved the expression and activity of ALDH2 and eNOS, and alleviated
      senescence-associated phenotypes in human aortic endothelial cells. Furthermore,
      ALDH2 deficiency impairs the dose-response protection of ethanol against
      endothelial senescence by promoting the accumulation of 4-HNE, the formation of 4
      HNE-SIRT1 protein adducts and the subsequent decrease in SIRT1-dependent p53
      deacetylation. Collectively, our data indicate that ALDH2 mediates the protection
      of appropriate ethanol by modulating SIRT1/p53-dependent endothelial senescence.

PMID- 30217445
TI  - Bioenergetic consequences of compromised mitochondrial DNA repair in the mouse
      heart.
AB  - The progeroid phenotype of mitochondrial DNA (mtDNA) mutator mice has been
      nebulously attributed to general mitochondrial 'dysfunction', though few studies
      have rigorously defined the bioenergetic consequences of accumulating mtDNA
      mutations. Comprehensive mitochondrial diagnostics was employed to interrogate
      the bioenergetic properties of isolated cardiac mitochondria from mtDNA mutator
      mice and wild type littermates. Assessment of respiratory flux in conjunction
      with parallel measurements of mitochondrial free energy all point to the cause of
      respiratory flux limitations observed in mtDNA mutator mouse mitochondria being
      due to impairments within the energy transduction step catalyzed by the electron
      transport system in which NADH/NAD+ free energy is transduced to the proton
      motive force (DeltaP). The primary bioenergetic consequence of this limitation
      appears to be hyper-reduction of NAD(P)H/NAD(P)+ redox poise across multiple
      substrate conditions, particularly evident at moderate to high respiration rates.
      This hyper-reduced phenotype appears to result from specific reductions in both
      complex I and complex IV expression, presumably due to compromised mtDNA
      integrity. Translation of these findings to the working heart would suggest that
      the primary biological consequence of accumulated mtDNA damage is accelerated
      electron leak driven by an increase in electron redox pressure for a given rate
      of oxygen consumption.

PMID- 30217446
TI  - ODC1 inhibits the inflammatory response and ROS-induced apoptosis in macrophages.
AB  - Macrophage activation plays a critical role in the innate immune response.
      Ornithine decarboxylase (ODC1) metabolizes l-ornithine to polyamines and is the
      rate-limiting enzyme involved in the metabolism of polyamines, which are
      reportedly involved in cell differentiation, proliferation, and migration.
      However, the function of ODC1 in immune cells and especially in macrophages, as
      well as its underlying molecular mechanism, remains unclear. This study revealed
      the potential ODC1 function and mechanism associated with the lipopolysaccharide
      (LPS)-, Bacillus Calmette-Guerin (BCG)-, or carbon tetrachloride (CCl4)-induced
      inflammatory response in macrophages. We found significant upregulation of ODC1
      in macrophages following LPS simulation and ODC1-specific suppression of
      proinflammatory cytokine secretion from macrophages upon stimulation with LPS,
      BCG and CCl4, respectively, suggesting a role as a common control element of the
      inflammatory response. Western blotting for nuclear factor-kappaB and mitogen
      activated protein kinases revealed significant inhibition of phosphorylation of
      multiple transcription factors following ODC1 overexpression in macrophages.
      Moreover, ODC1 inhibited reactive oxygen species-induced and caspase-dependent
      apoptosis highlighted by decreased caspase-3 and -9 expression following ODC1
      upregulation. These findings indicated that ODC1 was involved in attenuating the
      inflammatory response upon stimulation of macrophages, making it a potential
      therapeutic target for inflammatory diseases.

PMID- 30217447
TI  - Translocation-generated ITK-FER and ITK-SYK fusions induce STAT3 phosphorylation
      and CD69 expression.
AB  - Many cancer types carry mutations in protein tyrosine kinase (PTK) and such
      alterations frequently drive tumor progression. One category is gene
      translocation of PTKs yielding chimeric proteins with transforming capacity. In
      this study, we characterized the role of ITK-FER [Interleukin-2-inducible T-cell
      Kinase (ITK) gene fused with Feline Encephalitis Virus-Related kinase (FER) gene]
      and ITK-SYK [Interleukin-2-inducible T-cell Kinase (ITK) gene fused with the
      Spleen Tyrosine Kinase (SYK)] in Peripheral T Cell Lymphoma (PTCL) signaling. We
      observed an induction of tyrosine phosphorylation events in the presence of both
      ITK-FER and ITK-SYK. The downstream targets of ITK-FER and ITK-SYK were explored
      and STAT3 was found to be highly phosphorylated by these fusion kinases. In
      addition, the CD69 T-cell activation marker was significantly elevated. Apart
      from tyrosine kinase inhibitors acting directly on the fusions, we believe that
      drugs acting on downstream targets could serve as alternative cancer therapies
      for fusion PTKs.

PMID- 30217448
TI  - Up regulated Tmbim1 activation promotes high fat diet (HFD)-induced
      cardiomyopathy by enhancement of inflammation and oxidative stress.
AB  - The prevalence of cardiomyopathy due to metabolic stress has up-regulated
      dramatically; nevertheless, its molecular mechanisms remain unclear. Here we
      suggested that transmembrane BAX inhibitor motif-containing 1 (Tmbim1) is down
      regulated in the hearts of mice fed with high fat diet (HFD). We provided
      evidence that Tmbim1 knockout (KO) accelerated HFD-induced metabolic disorders in
      mice, as supported by the remarkable increase of fasting serum glucose and
      insulin levels. HFD-induced cardiac dysfunctions were greatly intensified by the
      loss of Tmbim1, along with higher levels of lactate dehydrogenase (LDH) and
      creatine kinase (CK) in serum. In addition, Tmbim1 deletion significantly
      enhanced lipid accumulation in heart of mice administrated with HFD. Furthermore,
      Tmbim1 knockout reinforced myocardial inflammation, evidenced by increasing the
      expression of pro-inflammatory cytokines (interleukin 1beta (IL-1beta), IL-6 and
      tumor necrosis factor-alpha (TNF-alpha)), and the activation of nuclear factor
      kappaB (NF-kappaB) signaling pathway. Tmbim1 deficiency strengthened oxidative
      damage in hearts of HFD-fed mice, accompanied with a significant reduction of
      nuclear factor-erythroid 2 related factor 2 (Nrf-2) pathway. In palmitate (PA)
      treated primary cardiomyocytes, Tmbim1 ablation markedly enhanced cell
      inflammation and oxidative stress, which were abolished by the suppression of ROS
      generation and NF-kappaB activation. Taken together, these findings suggested
      that Tmbim1 might be a key suppressor of metabolic stress-induced cardiomyopathy,
      which could be a promising target for the treatment of metabolic syndrome
      triggered myocardial damage and heart failure.

PMID- 30217449
TI  - Down-regulation of MAP2K1 by miR-539 inhibits hepatocarcinoma progression.
AB  - Liver cancer has been considered as one of the major leading causes of cancer
      related mortality. The incidence of liver cancer tends to increase in less
      developed regions. Increasing evidences have demonstrated that mircoRNAs (miRNAs)
      play crucial roles in the modulation of tumor growth and progression. Whereas,
      the functional role of miR-539 in hepatocellular carcinoma (HCC) is not well
      established. In our present study, we sought to explore biological role of miR
      539 in HCC progression. qRT-PCR was utilized to evaluate the expression level of
      miR-539. Immunoblotting analysis, qRT-PCR and luciferase reporter assays were
      used for the identification of the potential target of miR-539. Proliferation,
      migration and invasion assays and flow cytometric were performed to assess the
      biological functional role of miR-539. The molecular signaling pathways related
      to the integration of miR-539 were also evaluated. MiR-539 was reduced in human
      HCC. Mitogen-activated protein kinase 1, also known as MAP2K1 was verified as the
      target of miR-539. Overexpression of miR-539 inhibited migration, invasion and
      cell proliferation, while apoptosis rate was increased. Knockdown or
      overexpression of MAP2K1 in HCC cell transfected with ag-miR-539 or in-miR-539
      indicated that miR-539 suppresses the progression of HCC by directly targeting
      and regulating MAP2K1. Our results reveal that miR-539 might be a tumor
      suppressor in HCC, supporting a potential target for advanced therapeutic
      strategy for this disease.

PMID- 30217450
TI  - Activation of JNK signaling in osteoblasts is inversely correlated with collagen
      synthesis in age-related osteoporosis.
AB  - The age-related reduction in the function of osteoblasts plays a central role in
      the pathogenesis of bone loss and osteoporosis. Collagen synthesis is a primary
      function of differentiated osteoblasts, however, the mechanisms for age-related
      changes in collagen synthesis in human osteoblasts remain elusive. We use Gene
      Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) analysis to
      exploit the transcriptional profiles of osteoblasts from young and old donors. A
      panel of collagen members was downregulated in aged osteoblasts, including
      COL12A1, COL5A1, COL5A3, COL8A1 and COL8A2. Co-expression analysis followed by GO
      analysis revealed that oxidoreductase activity and kinase activity were inversely
      correlated with collagen synthesis in osteoblasts. GESA analysis further showed
      that JNK signaling was upregulated in aged osteoblasts. Consistently, MAP3K4 and
      MAP4K2, upstream of JNK, were also increased in aged osteoblasts. Moreover,
      expression levels of MAP3K4 were significantly inversely correlated with levels
      of the collagen genes. Those transcriptomic results were further verified by
      examining clinical specimens of osteoporosis by immunohistochemistry. These
      results provide transcriptomic evidence that deregulated JNK signaling may impair
      collagen synthesis in osteoblasts and imply a therapeutic value of JNK inhibitors
      for treating osteoporosis and preventing skeletal aging by counteracting the age
      related reduction in the function of osteoblasts.

PMID- 30217451
TI  - Dynamics of alternative polyadenylation in human preimplantation embryos.
AB  - Alternative polyadenylation (APA) affects the length of the 3' untranslated
      region (3'-UTR) and the regulation of microRNAs. Previous studies have shown that
      cancer cells tend to have shorter 3'-UTRs than normal cells. A plausible
      explanation for this is that it enables cancer cells to escape the regulation of
      microRNAs. Here, we extend this concept to an opposing context: changes in 3'-UTR
      length in the development of the human preimplantation embryo. Unlike cancer
      cells, during early development 3'-UTRs tended to become longer, and gene
      expression was negatively correlated with 3'-UTR length. Moreover, our functional
      enrichment results showed that length changes are part of the development
      mechanism. We also investigated the analogy of 3'-UTR length variation with
      respect to lncRNAs and found that, similarly, lncRNA length tended to increase
      during embryo development.

PMID- 30217452
TI  - Identification and characterization of a novel phosphoregulatory site on cyclin
      dependent kinase 5.
AB  - Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase essential for
      embryonic development whose overactivation has been implicated in several
      pathologies including neurodegeneration, cancer cell metastasis and type II
      diabetes. Therefore, it is important to investigate molecular mechanism(s) that
      mediate regulation of CDK5 activity. Here we identify and characterize a novel
      phosphoregulatory site on CDK5. Our mass spectrometry analysis identified seven
      putative phosphorylation sites on CDK5. Using phosphomimetic and non
      phosphorylatable mutants, we determined that phosphorylation of S47, one of the
      identified sites, renders the kinase catalytically inactive. The inactivation of
      the kinase due to the phosphomimetic change at S47 results from inhibition of its
      interaction with its cognate activator, p35. We connect the effect of this
      regulatory event to a cellular phenotype by showing that the S47D CDK5 mutant
      inhibits cell migration and promotes cell proliferation. Together, these results
      have uncovered a potential physiological mechanism to regulate CDK5 activity. The
      evolutionary placement of a phosphorylatable residue (S/T) at this position not
      only in CDK5 but also in the majority of other CDK family members suggests that
      this phosphosite may represent a shared regulatory mechanism across the CDK
      family.

PMID- 30217453
TI  - Deletion of JDP2 improves neurological outcomes of traumatic brain injury (TBI)
      in mice: Inactivation of Caspase-3.
AB  - Traumatic brain injury (TBI) is a major cause of death and disability, also
      resulting in long-term serious neurological impairment in survivors. However, the
      pathogenesis of TBI has not been fully understood. Jun dimerization protein 2
      (JDP2) is a member of the AP-1 family of transcription factors, containing a
      basic region-leucine zipper motif. JDP2 plays essential roles in various cellular
      processes, including differentiation, apoptosis, senescence and aging. In the
      study, we attempted to explore the effects of JDP2 on TBI progression both in
      vivo and in vitro. The wild type (WT) and JDP2 knockout (KO) mice were employed
      in our study and were subjected to TBI. The results showed that JDP2-deficient
      mice exhibited improved cognitive functions in TBI mice. The inflammatory
      cytokines, glial amount and apoptosis, as well as the protein of cleaved Caspase
      3 were significantly increased after TBI in WT mice, and all these up-regulation
      were significantly mitigated by JDP2 knockout in mice. We also found that TBI
      induced JDP2 expression in hippocampus of mice. Lipopolysaccharide (LPS) also
      stimulated JDP2 expression levels in astrocytes isolated from WT mice, indicating
      the critical role of JDP2 in TBI. Suppressing Caspase-3 activation could reduce
      LPS-induced inflammation in astrocytes. Consistent with the results in vivo, LPS
      induced inflammatory response and apoptosis were reversed by JDP2 deficiency in
      cells. Notably, we found that over-expressing JDP2 could further promoted
      inflammation, apoptosis and Caspase-3 activation induced by LPS. Collectively,
      JDP2 knockout effectively attenuate TBI in vivo and in vitro through blocking
      Caspase-3 activation, providing a potential therapeutic target for TBI or even
      other neurological disorders.

PMID- 30217454
TI  - A role for myosin VI in retinal pigment epithelium phagocytosis.
AB  - The retinal pigment epithelium (RPE) is a monolayer of pigmented cells adjacent
      to the choroid coat, the vascular layer of the eye. Among other functions, these
      cells are responsible for the phagocytosis of rod and cone cell waste shed from
      the photoreceptor outer segments. We describe here studies to understand the
      involvement of the motor protein myosin VI in the trafficking of internalized
      microspheres by a human retinal pigment epithelium primary cell line (ARPE-19).
      We perturbed the myosin VI-actin interaction by overexpressing a dominant
      negative myosin VI construct in these cells. We used single particle tracking to
      characterize the trajectories of internalized fluorescent microspheres. Analysis
      of the speed of the microspheres' motions revealed that the magnitude of the
      average speed over short time scales is reduced in the presence of the dominant
      negative motor. Analysis of the mean-squared displacement of these trajectories
      demonstrated that trafficking of phagosomes involves two modes of motion, a
      rapid, more randomly directed motion that is myosin VI dependent and a slower,
      more directed motion that is independent of the motor. From these data, we posit
      that this trafficking process involves an interplay between myosin VI motors,
      which are involved in motion through the actin periphery of the cell, and
      microtubule motors.

PMID- 30217455
TI  - 4-Hydroxybenzoic acid (4-HBA) enhances the sensitivity of human breast cancer
      cells to adriamycin as a specific HDAC6 inhibitor by promoting HIPK2/p53 pathway.
AB  - Breast cancer is reported a very complex disease along with heterogeneous
      morphological characteristics and unrelated clinical behavior, and is a leading
      cancer among female. Nevertheless, chemo-resistance is frequently observed.
      Adriamycin (ADM) is a always employed drug to treat clinical breast cancer.
      However, strong resistance to ADM limited its clinical efficacy. Deregulation of
      HDAC6 activity is linked to various diseases including cancer resulting in
      accumulating interest for developing HDAC6 inhibitors. In the present study, for
      the first time, we found that 4-Hydroxybenzoic acid (4-HBA), as histone
      deacetylase 6 (HDAC6) inhibitor, could successfully reverse ADM resistance in
      human breast cancer cells. 4-HBA significantly promoted the anticancer effect of
      ADM on apoptosis induction, as evidenced by the increased expressions of Caspase
      3 and PARP cleavage, which was associated with the promotion p53 and homeodomain
      interacting protein kinase-2 (HIPK2) expressions in ADM-resistant breast cancer
      cells. Furthermore, the suppressive effect of ADM on drug-resistant breast cancer
      cells was accelerated by 4-HBA through increasing the number of cells distributed
      in G2/M phase of cell cycle arrest. Inhibiting HIPK2/p53 pathway could abolish 4
      HBA/ADM co-treatment-induced apoptosis and G2/M cell cycle arrest. Importantly,
      HDAC6 expressions were also significantly down-regulated in ADM-resistance breast
      cancer cells co-treated with ADM and 4-HBA. Additionally, 4-HBA clearly
      potentiated the anticancer role of ADM in the MCF-7 breast cancer animal model
      with low toxicity. Therefore, 4-HBA could be applied as an effective HDAC6
      inhibitor to reverse human breast cancer resistance. Herein, the 4-HBA and ADM
      combination might represent as a useful therapeutic strategy to prevent human
      breast cancer.

PMID- 30217456
TI  - Crystal structure of p-nitrophenol 4-monooxygenase PnpA from Pseudomonas putida
      DLL-E4: The key enzyme involved in p-nitrophenol degradation.
AB  - p-Nitrophenol 4-monooxygenase PnpA, the key enzyme in the hydroquinone pathway of
      p-nitrophenol (PNP) degradation, catalyzes the monooxygenase reaction of PNP to p
      benzoquinone in the presence of FAD and NADH. Here, we determined the first
      crystal structure of PnpA from Pseudomonas putida DLL-E4 in its apo and FAD
      complex forms to a resolution of 2.04 A and 2.48 A, respectively. The PnpA
      structure shares a common fold with hydroxybenzoate hydroxylases, despite a low
      amino sequence identity of 14-18%, confirming it to be a member of the Class A
      flavoprotein monooxygenases. However, substrate docking studies of PnpA indicated
      that the residues stabilizing the substrate in an orientation suitable for
      catalysis are not observed in other homologous hydroxybenzoate hydroxylases,
      suggesting PnpA employs a unique catalytic mechanism. This work expands our
      understanding on the reaction mode for this enzyme class.

PMID- 30217457
TI  - Effects of Icaritin on the physiological activities of esophageal cancer stem
      cells.
AB  - Icaritin is a compound extracted from herb, recent study have found it is able to
      influence the activity of various types of cancer. Our aim was to investigate the
      effects of Icaritin on the physiological activities of esophageal cancer stem
      cells (CSCs). In this study, esophageal cancer cells were cultured and CD133
      positive esophageal CSCs were sorted by flow cytometry. Changes in the
      physiological activity of esophageal CSCs following treatment with different
      concentrations of Icaritin (0, 12.5, 25, 50, and 100 MUmol/L) were evaluated. The
      CCK-8 method and Transwell assay were used to determine the effects of Icaritin
      on the proliferation, migration, and invasion of esophageal CSCs. Flow cytometery
      was used to investigate its effect on the apoptosis of CSCs. The effect of
      Icaritin on the expression of proteins in Wnt and Hedgehog signaling pathways
      were determined using western blot test. Consequently, Icaritin inhibited the
      proliferation, migration, and invasion of esophageal CSCs in a dose-dependent
      manner. It promoted cell apoptosis, and influenced the levels of proteins in Wnt
      and Hedgehog signaling pathways. It may act as a promising drug in the therapy of
      esophageal cancer.

PMID- 30217458
TI  - Improving the availability of health research in languages other than English.

PMID- 30217459
TI  - American Joint Committee on Cancer staging system 7th edition versus 8th edition:
      any improvement for patients with squamous cell carcinoma of the tongue?
AB  - OBJECTIVE: In this study, we evaluated the 8th edition of American Joint
      Committee on Cancer (AJCC) staging criteria and lymph node ratio (LNR) to
      identify patients affected by squamous cell carcinoma of the tongue (SCCT) with a
      poor prognosis. STUDY DESIGN: Seventy-three cases of SCCT were analyzed
      retrospectively. Tumor staging was revised according to the 7th and 8th editions
      of the AJCC criteria. Depth of invasion (DOI), extranodal extension (ENE), and
      LNR were evaluated. RESULTS: Twenty-five cases were reclassified: 17 patients
      received an upstage in the staging score, and in 8 cases in the same stage group,
      pT or pN was changed. In the pT-upstaged group, 7 patients experienced
      recurrence, and 8 died. In the pN-upstaged group, 9 patients developed
      recurrence, and 10 died. The number of disease recurrence or death was higher in
      the groups of patients who received an upstage in pN and in the staging score (P
      < .05). The pN-upstaged group showed worse disease-free survival (DFS) and
      overall survival (OS) (P < .05). LNR was higher in patients with recurrence, and
      among these, LNR was lower in patients with ENE (P <.05). CONCLUSIONS: The 8th
      edition of the AJCC criteria allows for better stratification of patients with
      SCCT. The implementation of ENE and LNR to pN classification seems to identify
      patients with worse DFS and OS.

PMID- 30217461
TI  - No need to change dairy food dietary guidelines yet.

PMID- 30217460
TI  - Association of dairy intake with cardiovascular disease and mortality in 21
      countries from five continents (PURE): a prospective cohort study.
AB  - BACKGROUND: Dietary guidelines recommend minimising consumption of whole-fat
      dairy products, as they are a source of saturated fats and presumed to adversely
      affect blood lipids and increase cardiovascular disease and mortality. Evidence
      for this contention is sparse and few data for the effects of dairy consumption
      on health are available from low-income and middle-income countries. Therefore,
      we aimed to assess the associations between total dairy and specific types of
      dairy products with mortality and major cardiovascular disease. METHODS: The
      Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort
      study of individuals aged 35-70 years enrolled from 21 countries in five
      continents. Dietary intakes of dairy products for 136 384 individuals were
      recorded using country-specific validated food frequency questionnaires. Dairy
      products comprised milk, yoghurt, and cheese. We further grouped these foods into
      whole-fat and low-fat dairy. The primary outcome was the composite of mortality
      or major cardiovascular events (defined as death from cardiovascular causes, non
      fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were
      calculated using multivariable Cox frailty models with random intercepts to
      account for clustering of participants by centre. FINDINGS: Between Jan 1, 2003,
      and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major
      cardiovascular events [n=5855]) during the 9.1 years of follow-up. Higher intake
      of total dairy (>2 servings per day compared with no intake) was associated with
      a lower risk of the composite outcome (HR 0.84, 95% CI 0.75-0.94; ptrend=0.0004),
      total mortality (0.83, 0.72-0.96; ptrend=0.0052), non-cardiovascular mortality
      (0.86, 0.72-1.02; ptrend=0.046), cardiovascular mortality (0.77, 0.58-1.01;
      ptrend=0.029), major cardiovascular disease (0.78, 0.67-0.90; ptrend=0.0001), and
      stroke (0.66, 0.53-0.82; ptrend=0.0003). No significant association with
      myocardial infarction was observed (HR 0.89, 95% CI 0.71-1.11; ptrend=0.163).
      Higher intake (>1 serving vs no intake) of milk (HR 0.90, 95% CI 0.82-0.99;
      ptrend=0.0529) and yogurt (0.86, 0.75-0.99; ptrend=0.0051) was associated with
      lower risk of the composite outcome, whereas cheese intake was not significantly
      associated with the composite outcome (0.88, 0.76-1.02; ptrend=0.1399). Butter
      intake was low and was not significantly associated with clinical outcomes (HR
      1.09, 95% CI 0.90-1.33; ptrend=0.4113). INTERPRETATION: Dairy consumption was
      associated with lower risk of mortality and major cardiovascular disease events
      in a diverse multinational cohort. FUNDING: Full funding sources are listed at
      the end of the paper (see Acknowledgments).

PMID- 30217463
TI  - Thiazole- and selenazole-comprising high-affinity inhibitors possess bright
      microsecond-scale photoluminescence in complex with protein kinase CK2.
AB  - A previously disclosed protein kinase (PK) CK2-selective inhibitor 4-(2-amino-1,3
      thiazol-5-yl)benzoic acid (ATB) and its selenium-containing counterpart (ASB)
      revealed remarkable room temperature phosphorescence when bound to the ATP pocket
      of the protein kinase CK2. Conjugation of these fragments with a mimic of CK2
      substrate peptide resulted in bisubstrate inhibitors with increased affinity
      towards the kinase. Attachment of the fluorescent acceptor dye 5-TAMRA to the
      conjugates led to significant enhancement of intensity of long-lifetime
      (microsecond-scale) photoluminescence of both sulfur- and selenium-containing
      compounds. The developed photoluminescent probes make possible selective
      determination of the concentration of CK2 in cell lysates and characterization of
      CK2 inhibitors by means of time-gated measurement of photoluminescence.

PMID- 30217462
TI  - Anti-obesity action of INDUS810, a natural compound from Trigonella foenum
      graecum: AMPK-dependent lipolysis effect in adipocytes.
AB  - OBJECTIVE: We investigated the anti-obesity effect and underlying action
      mechanism of INDUS810 isolated from Trigonella foenum-graecum L. (Fabaceae), an
      annual herb commonly known as fenugreek and reported to have hypocholesterolemic,
      antidiabetic, anticancer and gastroprotective properties. METHODS: For obese
      animal study, 4-week old mice were fed with normal diet or high-fat diet together
      with or without intraperitoneal injection of INDUS810 (200mg/kg) twice per week
      for 15weeks. 3T3-L1 cells were used to study action mechanism of INDUS810 in
      adipocyte differentiation and lipid metabolism. RESULTS: We found that INDUS810
      can reduce high-fat diet-induced weight increase in epididymal white adipose
      tissue, interscapular brown adipose tissue and liver, as well as serum levels of
      total cholesterol and low-density lipoprotein cholesterol. Moreover, the insulin
      sensitivity was significantly improved in INDUS810-treated obese mice. In 3T3-L1
      adipocytes, we found that INDUS810 could inhibit lipid accumulation at either
      differentiating or mature stages, and increase lipolysis activity in mature
      adipocytes. Additionally, INDUS810 has no effects on cell viability nor the
      expressions of adipocyte differentiation markers like fatty acid synthase,
      peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding
      protein alpha. In contrast, INDUS810 can increase protein levels of peroxisome
      proliferator-activated receptor alpha, peroxisome-proliferator-activated receptor
      gamma co-activator 1beta, sirtuin 1 and sirtuin 3. Of note, INDUS810 can activate
      adenosine monophosphate-activated protein kinase, which leads to the reduction of
      lipid contents in adipocytes. CONCLUSION: Our in vitro and in vivo studies
      suggest that INDUS810 is a potential anti-obesity agent, and this action depends
      on activate adenosine monophosphate-activated protein kinase activation.

PMID- 30217464
TI  - Synthesis of oxidative metabolites of CRA13 and their analogs: Identification of
      CRA13 active metabolites and analogs thereof with selective CB2R affinity.
AB  - CRA13; a peripheral dual CB1R/CB2R agonist with clinically proven analgesic
      properties, infiltrates into CNS producing adverse effects due to central CB1R
      agonism. Such adverse effects might be circumvented by less lipophilic compounds
      with attenuated CB1R affinity. Metabolism produces less lipophilic metabolites
      that might be active metabolites. Some CRA13 oxidative metabolites and their
      analogues were synthesized as less lipophilic CRA13 analogues. Probing their CB1R
      and CB2R activity revealed the alcohol metabolite 8c as a more potent and more
      effective CB2R ligand with attenuated CB1R affinity relative to CRA13. Also, the
      alcohol analogue 8b and methyl ester 12a possessed enhanced CB2R affinity and
      reduced CB1R affinity. The CB2R binding affinity of alcohol analogue 8b was
      similar to CRA13 while that of methyl ester 12a was more potent. In silico study
      provided insights into the possible molecular interactions that might explain the
      difference in the elicited biological activity of these compounds.

PMID- 30217465
TI  - Activation of alpha7 nicotinic acetylcholine receptor alleviates Abeta1-42
      induced neurotoxicity via downregulation of p38 and JNK MAPK signaling pathways.
AB  - Amyloid beta peptide 1-42 (Abeta1-42) could induce cognitive deficits through
      oxidative stress, inflammation, and neuron death in Alzheimer's disease (AD).
      MAPK pathways have been thought to mediate Abeta1-42-induced neuroinflammation
      responses, neuron death and cognitive decline in AD. The alpha7 nicotinic
      acetylcholine receptor (alpha7nAChR) exerts a neuroprotective effect. However,
      whether alpha7nAChR alleviates Abeta1-42-induced neurotoxicity through MAPKs
      (p38, ERK, JNK) in vivo remains unclear. In our study, memory was assessed in
      C57BL/6 mice using a Y-maze test. Cell death was assessed by Nissl and Hoechst
      staining and Bax, Bcl-2, Caspase 3, and Cytochrome C levels using Western
      blotting. Oxidative stress was assayed by superoxide dismutase (SOD), catalase
      (CAT), and malondialdehyde (MDA) levels. Inflammation was examined with GFAP and
      Iba1 using immunohistochemistry. The Abeta degrading enzymes insulin degrading
      enzyme (IDE) and neprilysin (NEP) were tested using Western blotting. We found
      that activating alpha7nAChR or inhibiting p38 or JNK pathway alleviated Abeta1-42
      induced cognitive deficits and neuron loss and death by reducing oxidative
      stress. In addition, activating alpha7nAChR or inhibiting p38 or JNK pathway also
      reduced inflammation, which was observed as reduced GFAP and Iba1 levels with
      different effects on Abeta degrading enzymes. Finally, we found that the
      activation of alpha7nAChR led to the downregulation of pp38 and pJNK levels.
      Conversely, the inhibition of p38 or JNK resulted in the upregulation of
      alpha7nAChR levels in the hippocampus and cortex. Our data indicate that the
      activation of alpha7nAChR alleviates Abeta1-42-induced neurotoxicity, and this
      protective effect might act through the downregulation of p38 and JNK MAPKs.

PMID- 30217466
TI  - Tricalcium Silicate Capping Materials Modulate Pulp Healing and Inflammatory
      Activity In Vitro.
AB  - INTRODUCTION: On stimulation by lipoteichoic acid or by a physical injury,
      fibroblasts have been shown to play a major role in the initiation of the pulp
      inflammatory reaction and healing through secretion of complement proteins and
      growth factors. The application of direct pulp-capping materials on these cells
      may interfere with the inflammatory and the healing processes within the pulp's
      inextensible environment. This work was designed to study in vitro the effects of
      silicate-based materials on pulp fibroblast modulation of the initial steps of
      pulp inflammation and healing. METHODS: The effects of Biodentine, TheraCal, and
      Xeno III eluates were studied on lipoteichoic acid-stimulated and physically
      injured fibroblasts. Cytokine secretion (interleukin 6, vascular endothelial
      growth factor, fibroblast growth factor-2, and transforming growth factor-beta1)
      was quantified by enzyme-linked immunosorbent assay. Inflammatory THP-1 adhesion
      to endothelial cells and their migration and activation were studied in vitro.
      Human pulp fibroblast proliferation was investigated with the MTT test, and their
      migration to the injury site was studied with the scratch healing assay. RESULTS:
      Interleukin 6 and vascular endothelial growth factor secretion increased with all
      materials but to a lesser extent with Biodentine. Fibroblast growth factor-2 and
      transforming growth factor-beta1 secretion was significantly higher with
      Biodentine than with all other materials. THP-1 cell adhesion to endothelial
      cells and their activation were reduced by Biodentine and TheraCal. However,
      their migration decreased only with Biodentine. Fibroblast proliferation
      significantly increased with Biodentine but significantly decreased with Xeno III
      after day 6. Finally, only Biodentine induced fibroblast migration to the injury
      site in the scratch assay. CONCLUSIONS: These results confirm that pulp-capping
      materials affect the early steps of pulp inflammation and healing. They show that
      Biodentine had the highest pulp healing and anti-inflammatory potential when
      compared with the resin-containing materials. This highlights the interest of the
      material choice for direct pulp-capping.

PMID- 30217467
TI  - Multi-target plasmid controls for conventional and real-time PCR-based serotyping
      of Streptococcus pneumoniae.
AB  - BACKGROUND: Serotyping of Streptococcus pneumoniae is an integral part of disease
      surveillance, with over 92 serotypes characterized to date using traditional
      serotyping. To identify the most predominant disease causing serotypes, molecular
      serotyping methods are now increasingly being used, like conventional and real
      time multiplex PCR (cmPCR and rmPCR, respectively). Given that cmPCR consists of
      eight reactions spanning 41 targets, and rmPCR consists of seven triplex
      reactions, standardizing positive controls for these assays is challenging. As
      such, a 43-target plasmid for cmPCR (pSpn-CM1) and a 23 target plasmid for rmPCR
      (pSpn-RM1) were designed and validated. METHODS: Plasmid pSpn-RM1 was designed
      and synthesized as chimeric DNA sequences to include all PCR target primer
      binding sites sequences for cmPCR. Plasmid pSpn-RM1 consisted of all primer and
      probe sequences required for rmPCR. Additional targets (lytA and cpsA) were
      included in both plasmids for quantification, following their propagation and
      purification from Escherichia coli. RESULTS: When tested using the cmPCR
      reactions, all targets could be reproducibly be detected using pSpn-CM1 as
      template, with good amplicon visibility at a concentration of 1.4 (+/- 0.3) * 105
      copies/ml was used. For the rmPCR reactions, all targets were reproducibly
      amplified with a concentration of 1.1 (+/- 0.2) * 104 copies/ml of pSpn-RM1, and
      the PCR efficiency for each target was equivalent to DNA extracted from
      representative S. pneumoniae serotypes. CONCLUSIONS: These quantifiable multi
      target plasmids simplify the preparation of controls for PCR-based serotyping of
      S. pneumoniae, and methods herein could be extended to other highly multiplexed
      PCR assays.

PMID- 30217468
TI  - Developmental regulation of type 1 and type 3 interferon production and risk for
      infant infections and asthma development.
AB  - BACKGROUND: Virus-associated febrile lower respiratory tract infections (fLRIs)
      during infancy have been identified as risk factors for persistent wheeze
      development. We hypothesized that variations in innate immune defense capacity
      during this period, as exemplified by production of type 1 and 3 interferons
      (T1/3IFNs), might be an underlying determinant of risk. OBJECTIVE: We sought to
      investigate relationships between postnatal development of innate interferon
      response capacity and susceptibility to early infections and persistent wheeze.
      METHODS: We studied a subset of subjects from a birth cohort at high risk for
      asthma/allergy and determined the capacity of cord blood cells (n = 151) to
      produce any of a panel of 17 T1/3IFNs in response to the viral mimic polyinosinic
      polycytidylic acid using a sensitive PCR assay. We investigated relationships
      between neonatal interferon responses and lower respiratory tract infection
      history during infancy, wheezing history to 5 age years, and ensuing maturation
      of innate immune capacity by age 4 years (n = 160) and 10 years (n = 125).
      RESULTS: Although cohort subjects produced an average of 2.6 +/- 0.3 of the 17
      innate interferons tested at birth, 24% showed no T1/3IFN production. This
      nonproducer subgroup showed increased risk for infant fLRIs (odds ratio, 2.62;
      95% CI, 1.14-6.06; P = .024) and persistent wheeze (odds ratio, 4.24; 95% CI,
      1.60-11.24; P = .004) at age 5 years relative to those producing 1 or more
      T1/3IFNs, whereas risk for infant wheezy lower respiratory tract infections or
      "transient early wheeze" was unaffected. Moreover, infants who experienced fLRIs
      subsequently demonstrated accelerated development of T1/3IFN response capacity
      between 1 and 4 years of age. CONCLUSIONS: T1/3IFN response capacity appears
      strongly developmentally constrained at birth. Infants in whom this negative
      regulation is strongest manifest increased risk for severe respiratory tract
      infections during infancy and subsequent persistent wheeze.

PMID- 30217469
TI  - The Corneal Dystrophies-Does the Literature Clarify or Confuse?

PMID- 30217470
TI  - Poor nutritional status but not cognitive or functional impairment per se
      independently predict 1 year mortality in elderly patients with hip-fracture.
AB  - BACKGROUND & AIMS: Hip fractures are strongly associated with mortality in the
      elderly. Studies investigating predisposing factors have suggested a negative
      impact of poor nutritional, cognitive and functional status on patient survival,
      however their independent prognostic impact as well as their interactions remain
      undefined. This study aimed to determine whether poor nutritional status
      independently predicts 1 year post-fracture mortality after adjusting for
      cognitive and functional status and for other clinically relevant covariates.
      METHODS: 1211 surgically treated hip fracture elderly (age >= 65) patients
      consecutively admitted to the Orthopaedic Surgery Unit of the "Azienda Sanitaria
      Universitaria Integrata Trieste" (ASUITs), Cattinara Hospital, Trieste, Italy and
      managed by a dedicated orthogeriatric team. Pre-admission nutritional status was
      evaluated by Mini Nutritional Assessment (MNA) questionnaire, cognitive status by
      Short Portable Mental Status Questionnaire (SPMSQ) and functional status by
      Activity of Daily Living (ADL) questionnaire. All other clinical data, including
      comorbidities, type of surgery, post-operative complications (delirium, deep vein
      thrombosis, cardiovascular complications, infections, need for blood
      transfusions) were obtained by hospital clinical records and by mortality
      registry. RESULTS: Poor nutritional status (defined as MNA <=23.5), increased
      cognitive and functional impairment were all associated with 3-, 6- and 12 month
      mortality (p < 0.001). Both cognitive and functional impairment were associated
      with poor nutritional status (p < 0.001). Logistic regression analysis
      demonstrated that the association between nutritional status and 3-, 6- and 12-
      month mortality was independent of age, gender, comorbidities, type of surgery
      and post-operative complications as well as of cognitive and functional
      impairment (p < 0.001). In contrast, the associations between mortality and
      cognitive and functional impairment were independent (p < 0.001) of demographic
      (age, gender) and clinical covariates but not of malnutrition. Kaplan-Meier
      analysis showed a lower mean survival time (p < 0.001) in patients with poor
      nutritional status compared with those well-nourished. CONCLUSIONS: In hip
      fracture elderly patients, poor nutritional status strongly predicts 1 year
      mortality, independently of demographic, functional, cognitive and clinical risk
      factors. The negative prognostic impact of functional and cognitive impairment on
      mortality is mediated by their association with poor nutritional status.

PMID- 30217471
TI  - Between-meal sucrose-sweetened beverage consumption impairs glycaemia and lipid
      metabolism during prolonged sitting: A randomized controlled trial.
AB  - BACKGROUND & AIMS: Chronic overconsumption of sugar-sweetened beverages (SSBs) is
      associated with unfavourable health effects, including promotion of obesity.
      However, the acute effects of consuming SSBs on glucose and lipid metabolism
      remain to be characterized in a real-world, post-prandial context of prolonged
      sitting. We quantified the acute effects of between-meal SSB consumption compared
      with water, on glucose and lipid metabolism in habitual soft drink consumers
      during prolonged sitting. METHODS: Twenty-eight overweight or obese young adults
      [15 males; 23 +/- 3 (mean +/- SD) years, body mass index (BMI) 31.0 +/- 3.6
      kg/m2) participated. During uninterrupted sitting and following standardized
      breakfast and lunch meals, each participant completed two 7-h conditions on
      separate days in a randomized, crossover design study. For each condition,
      participants consumed either a sucrose SSB or water mid-morning and mid
      afternoon. Peak responses and total area under the curve (tAUC) over 7 h for
      blood glucose, insulin, C-peptide, triglyceride and non-esterified fatty acid
      (NEFA) concentrations were quantified and compared. RESULTS: Compared to water,
      SSB consumption significantly increased the peak responses for blood glucose (20
      +/- 4% (mean +/- SEM)), insulin (43 +/- 15%) and C-peptide (21 +/- 6%)
      concentrations. The tAUC for all these parameters was also increased by SSB
      consumption. The tAUC for triglycerides was 15 +/- 5% lower after SSBs and this
      was driven by males (P < 0.05), as females showed no difference between
      conditions. The tAUC for NEFAs was 13 +/- 5% lower after the SSB condition (P <
      0.05). CONCLUSIONS: Between-meal SSB consumption significantly elevated plasma
      glucose responses, associated with a sustained elevation in plasma insulin
      throughout a day of prolonged sitting. The SSB-induced reduction in circulating
      triglycerides and NEFAs indicates significant modulation of lipid metabolism,
      particularly in males. These metabolic effects may contribute to the development
      of metabolic disease when SSB consumption is habitual and co-occurring with
      prolonged sitting. Clinical Trial Registry number: ACTRN12616000840482,
      https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12616000840482.

PMID- 30217472
TI  - Phenotyping Whole Forests Will Help to Track Genetic Performance.
AB  - Phenotyping is the accurate and precise physical description of organisms.
      Accurate and quantitative phenotyping underpins the delivery of benefits from
      genetic improvement programs in agriculture. In forest trees, phenotyping at an
      equivalent precision has been impossible because trees and forests are large,
      long-lived, and highly variable. These facts have restricted the delivery of
      genetic gains in forestry compared to other agricultural sectors. We describe a
      landscape-scale phenotyping platform that integrates remote sensing, spatial
      information systems, and genomics to facilitate the delivery of greater gains
      enabling forestry to catch up with other sectors. Combining remote sensing at a
      range of spatial and temporal scales with genomics will ultimately impact on tree
      breeding globally.

PMID- 30217473
TI  - Patterns of Relative Telomere Length is Associated With hTERT Gene Expression in
      the Tissue of Patients With Breast Cancer.
AB  - BACKGROUND: Homeostasis of telomere in breast cancer might be altered as a result
      of cumulative effects of various factors causing genomic instability and
      affecting prognosis. This study aimed to compare the relative telomere length
      (RTL) and hTERT mRNA expression in the tissue of patients with breast cancer
      along with the clinicopathologic parameters. PATIENTS AND METHODS: Frozen tumor
      tissues and adjacent normal breast tissue from 98 patients with invasive ductal
      breast cancer were used for the analysis. RTL and hTERT mRNA expression were
      measured using quantitative real time polymerase chain reaction. RESULTS: Among
      the 98 cases, 51% had an early-stage carcinoma, 66% were tumor size < 5 cm, 30%
      were node-negative, and 20% were low-grade tumors. In this study, 63% of cases
      showed higher hTERT gene expression with an odds ratio of 2.77 (P = .02). The
      median RTL for elongated telomere was 3.49, and the value was significantly
      elevated when compared with the shorter telomere. Shortened RTL was present in
      60% of early-stage cancer cases, 55% where the tumor size was < 5 cm, 72% of the
      lymph node-negative cases, and 68% of low-grade carcinoma. Significantly
      elongated RTL, with median 4.22, 3.19, 3.17, and 3.28 was observed (P < .05) in
      the advanced stage, larger tumor size, node-positive, and high-grade cases
      respectively. CONCLUSION: In this study, shortened telomere was observed in early
      stage cancer, and elongated telomere was found in advanced diseases. However, 13%
      of patients with lower hTERT gene expression showed elongated telomeres,
      indicating relative telomere length measurement in tissue is different from blood
      leukocyte, showing the dynamic process of tumorigenesis in tissue.

PMID- 30217474
TI  - Estimating abortion incidence among adolescents and differences in postabortion
      care by age: a cross-sectional study of postabortion care patients in Uganda.
AB  - OBJECTIVES: To provide the first estimate of adolescents' abortion incidence in
      Uganda and to assess differences in the abortion experiences and morbidities of
      adolescent and nonadolescent postabortion care (PAC) patients. STUDY DESIGN: We
      used the age-specific Abortion Incidence Complications Method, drawing from three
      surveys conducted in Uganda in 2013: a nationally representative Health
      Facilities Survey (n=418), a Health Professionals Survey (n=147) and a
      Prospective Morbidity Survey of PAC patients (n=2169). Multivariable logistic and
      Cox proportional hazard models were used to compare adolescent and nonadolescent
      PAC patients on dimensions including pregnancy intention, gestational age,
      abortion safety, delays to care, severity of complications and receipt of
      postabortion family planning. We included an interaction term between adolescents
      and marital status to assess heterogeneity among adolescents. RESULTS: Adolescent
      women have the lowest abortion rate among women less than 35 years of age (28.4
      abortions per 1000 women 15-19) but the highest rate among recently sexually
      active women (76.1 abortions per 1000 women 15-19). We do not find that
      adolescents face greater disadvantages in their abortion care experiences as
      compared to older women. However, unmarried PAC patients, both adolescent and
      nonadolescent, have higher odds of experiencing severe complications than
      nonadolescent married women. CONCLUSIONS: The high abortion rate among sexually
      active adolescents highlights the critical need to improve adolescent family
      planning in Uganda. Interventions to prevent unintended pregnancy and to reduce
      unsafe abortion may be particularly important for unmarried adolescents. Rather
      than treating adolescents as a homogenous group, we need to understand how
      marriage and other social factors shape reproductive health outcomes.
      IMPLICATIONS: This paper provides the first estimate of the adolescent abortion
      rate in Uganda. Studies of adolescent abortion and reproductive health must
      account for sexual activity and marital status. Further, interventions to address
      unintended pregnancy and unsafe abortion among unmarried women of all ages in
      Africa should be a priority.

PMID- 30217475
TI  - A systematic review of psychosocial explanations for the relationship between
      socioeconomic status and body mass index.
AB  - A negative association between socioeconomic status (SES) and levels of
      overweight/obesity is consistently found in high- and middle-income countries.
      Yet, there is little conclusive evidence about the mechanisms driving this
      association. In this systematic review, we discuss and compare the results of 22
      studies that examine the role of psychosocial mediators in the association
      between SES and BMI in diverse population samples. These include factors related
      to resources and constraints in one's external neighborhood, social resources,
      and psychological factors such as stress. The findings support theoretical models
      indicating that SES is related to BMI partially through environmental and
      psychological factors. Importantly, SES often remains a significant predictor of
      weight status, indicating the importance of also addressing structural
      antecedents in order to improve health among lower SES populations. We thoroughly
      discuss the quality and limitations of current study designs and mediation
      testing and provide recommendations for future research.

PMID- 30217476
TI  - Electroencephalogram alertness responses to blue light stimulus in elderly people
      with cataract.
AB  - Daytime blue light exposure can reduce fatigue and increase alertness in young
      healthy adults. Little is known of the daytime blue light influence on alertness
      in elders. A prospective with-in subject study was carried out in Peking
      University Third Hospital to evaluate the impact of cataract surgery on visual
      functions and the electroencephalogram alertness response to blue light stimulus
      before and after surgery. 14 participants diagnosed with age-related cataract
      were scheduled for monocular cataract surgery with ultraviolet-filtering
      intraocular lens (IOL) implantation. Best corrected visual acuity (BCVA), color
      discrimination and electroencephalogram results were measured before and after
      surgery. Exposure to blue light resulted in decreased delta (0.25-3.00 Hz)
      activity and increased beta (13.25-30.00 Hz) activity both before and after
      cataract surgery. Significant improvements in the BCVA and Farnsworth-Munsell-100
      hue total error scores were found after cataract surgery. The partial error
      scores in the red-yellow, green blue-blue, and blue purple-purple red bands also
      showed significant differences, with the green blue-blue band showing the most
      obvious improvement. Day-time blue light stimulus can increase alertness in
      elderly people with significant cataracts. Cataract surgery with ultraviolet
      filtering IOL implantation can increase light, particularly blue light
      transmittance. Opaque lens removal does not increase the alertness responses to
      blue light 1 day after surgery. Nevertheless, the increase in light especially
      blue light perception can be beneficial for the health of elder people in the
      long run.

PMID- 30217477
TI  - Effects of methylglyoxal on RANKL-induced osteoclast differentiation in RAW264.7
      cells.
AB  - Methylglyoxal (MG) is a reactive dicarbonyl compound produced by glycolytic
      processing, which has been identified as a precursor of advanced glycation end
      products. Elevated MG levels in patients with diabetes are believed to contribute
      to diabetic complications, including bone defects. The objective of this study
      was to evaluate the effect of MG on RANKL-induced osteoclast differentiation in
      RAW264.7 cells, a murine macrophage cell line. RAW264.7 cells were cultured in
      medium containing 50 ng/mL RANKL and different concentrations of MG. Tartrate
      resistant acid phosphatase (TRAP) activity and osteoclast bone resorbing activity
      were assessed and changes in intracellular calcium concentration, mitochondrial
      mass, mitochondrial membrane potential, and glyoxalase I level were examined. In
      addition, real-time RT-PCR assay was used to analyse osteoclast-associated genes.
      MG markedly inhibited RANKL-induced TRAP activity. MG treatment resulted in a
      significant decrease in intracellular calcium concentration, mitochondrial mass,
      mitochondrial membrane potential, and glyoxalase I level during
      osteoclastogenesis. In addition, MG increased the formation of mitochondrial
      superoxide. Quantitative reverse transcriptase-polymerase chain reaction revealed
      increased expression of the TRAF6, GAB2, ERK1, c-Fos, NFATc1, CLCN7, and OSTM1
      genes, decreased expression of TCIRG and carbonic anhydrase II, and unchanged
      expression of cathepsin K and MMP-9 upon MG treatment. MG had no effect on the
      bone resorbing activity of osteoclasts. Our findings indicate that MG inhibits
      TRAP and glyoxalase I activity and impairs mitochondrial function in osteoclasts.
      Further validation of the underlying pathway is necessary.

PMID- 30217478
TI  - Efficacy of atropine sulfate/obidoxime chloride co-formulation against sarin
      exposure in guinea pigs.
AB  - The efficacy and pharmacokinetics of the aqueous co-formulation contents of the
      TrobigardTM (atropine sulfate, obidoxime chloride) auto-injector were evaluated
      in a sarin exposed guinea pig model. Two subcutaneous (sc) sarin challenge doses
      were evaluated in guinea pigs instrumented with brain and heart electrodes for
      electroencephalogram (EEG) and electrocardiogram (ECG). Sarin challenge doses
      were chosen to reflect exposure subclasses with sublethal (moderate to severe
      clinical signs) and lethal consequences. The level of protection of intramuscular
      human equivalent doses of the co-formulation was defined by (1) the mitigation of
      signs and symptoms at a sublethal level and (2) the increase of survival time at
      the supralethal sarin dose levels. Pharmacokinetics of both atropine sulfate and
      obidoxime were proportional at 1 and 3 human equivalent doses, and only a small
      increase in heart rate was observed briefly as a side effect. At both sarin
      challenge doses, 54 MUg/kg and 84 MUg/kg, the co-formulation treatment was
      effective against sarin-induced effects. Survival rates were improved at both
      sarin challenge levels, whereas clinical signs and changes in EEG activity could
      not in all cases be effectively mitigated, in particular at the supralethal sarin
      challenge dose level. Reactivation of sarin inhibited cholinesterase was observed
      in blood, and higher brain cholinesterase activity levels were associated with a
      better clinical condition of the co-formulation treated animals. Although the
      results cannot be directly extrapolated to the human situation, pharmacokinetics
      and the effects over time related to plasma levels of therapeutics in a freely
      moving guinea pig could aid translational models and possibly improve prediction
      of efficacy in humans.

PMID- 30217479
TI  - 4'-hydroxywogonin inhibits colorectal cancer angiogenesis by disrupting PI3K/AKT
      signaling.
AB  - Angiogenesis is fundamental for solid tumor growth and metastasis, and anti
      angiogenic therapy has been an important therapeutic option for cancer treatment.
      Colorectal cancer (CRC) represents the fourth leading cause of cancer-related
      death worldwide. The current studies were aimed at investigating the anti
      angiogenic effects of the natural compound 4'-hydroxywogonin (4'-HW) on CRC
      related angiogenesis. Human CRC cell line SW620 cells and normal human intestinal
      epithelial HIEC cells were cultured and treated with interleukin-6 to mimic the
      tumor inflammatory microenvironment. Our data showed that 4'-HW reduced the
      viability of SW620 cells in a concentration- and time-dependent manner. 4'-HW
      also suppressed the proliferation of SW620 cells, but had little effect on the
      viability of HIEC cells. Moreover, 4'-HW concentration-dependently decreased the
      mRNA and protein expression of vascular endothelial growth factor-A (VEGF-A), the
      predominant pro-angiogenic cytokine in tumor angiogenesis. Subsequently, 4'-HW
      concentration-dependently inhibited the phosphorylation of phosphatidylinositol 3
      kinase (PI3K) and AKT. PI3K inhibitor wortmannin, similar to 4'-HW, significantly
      downregulated the VEGF-A expression in SW620 cells, and combination of wortmannin
      and 4'-HW produced more significant effects. Finally, human umbilical vein
      endothelial cells (HUVECs) incubated with the conditioned medium of 4'-HW-treated
      SW620 cells exhibited impaired angiogenic capacity at Matrigel. Incubation with
      the neutralizing antibody against VEGF-Aalone also suppressed the angiogenic
      properties of HUVECs in vitro. Collectively, 4'-HW decreased the viability and
      reduced angiogenesis in CRC, which was associated with downregulation of VEGF-A
      expression by disrupting the PI3K/AKT pathway. Our discoveries suggested 4'-HW as
      a promising anticancer agent against CRC targeting angiogenesis.

PMID- 30217480
TI  - Magnetic Resonance-guided Radiotherapy - Can We Justify More Expensive
      Technology?

PMID- 30217481
TI  - The equations of the inserted length of percutaneous central venous catheters on
      neonates in NICU.
AB  - BACKGROUND: In neonatal intensive care units, a percutaneous central venous
      catheter (PCVC) is inserted peripherally and threaded into a central venous
      location, when intravenous access is anticipated for an extended period of time.
      The tip location of PCVCs should be checked by an X-ray after the procedure. The
      present study aimed to determine an equation to estimate the optimal insertion
      length of PCVCs in neonates prior to the procedure. METHODS: The data of all
      neonates who had PCVC insertion between May 1st 2015 and April 30th 2016 was
      reviewed. Their gender, body weight and body length at the insertion date, any
      complications and the tip culture of their PCVCs were recorded. The tip location
      of the PCVC, which was confirmed by X-ray, was either in the inferior vena cava
      near to the diaphragm or in the superior vena cava before the right atrial
      junction, depending on the insertion site. We analyzed the correlation among
      inserted length of PCVCs, body weight and body length by linear regression to
      determine an equation for estimating the optimal insertion length of PCVCs. The
      accuracy of the equations was evaluated prospectively by Pearson's correlation
      analysis, and the adjusting rate of PCVCs after the initial insertion was
      compared between the traditional method and using the equation. RESULTS: The
      equation of PCVCs inserted in the foot was "insertion length (cm) = 16 + 4.27 *
      body weight (kg)", in the femoral vein was "inserted length (cm) = 9.8 + 1.7 *
      body weight (kg)", in the popliteal vein was "inserted length (cm) = -0.3 + 0.45
      * body length (cm)", in the hand was "inserted length (cm) = 4.46 + 0.32 * body
      length (cm)", and in the axillary vein was inserted length (cm) = 1 + 0.18 * body
      length (cm). The adjusting rate of PCVCs after initial insertion was decreased
      from 73.5% to 53% following use of the equation. CONCLUSIONS: Equations provided
      a convenient and accurate method to estimate the optimal insertion length of
      PCVCs before their placement.

PMID- 30217482
TI  - The role of prophylactic gastrectomy in patients with juvenile polyposis
      syndrome.

PMID- 30217483
TI  - A moderate exposure to perfluorooctanoic acid causes persistent DNA damage and
      senescence in human epidermal HaCaT keratinocytes.
AB  - Perfluorooctanoic acid has been used widespread, during the last decades, in a
      number of consumer and industrial products. Although this compound has been
      subjected to extensive epidemiological and toxicological studies, limited data
      are available concerning its potential dermal toxicity in mammalian cells. In
      this study, we used a two-stage approach with relevant cytotoxicity endpoints
      including cell viability and proliferation, oxidative stress, DNA damage and cell
      senescence to assess the immediate and the long-lasting or delayed cytotoxicity
      caused by the compound in HaCaT keratinocytes. Our results suggest that a single
      exposure to perfluorooctanoic acid causes concentration-dependent changes in cell
      proliferation that were not restored during a 48 h recovery period. Furthermore,
      we demonstrate that a moderate treatment with this perfluorochemical causes
      persistent DNA damage, which ultimately leads to development of the senescence
      associated secretory phenotype in HaCaT cells. This paper provides unprecedented
      data and insights regarding the cytotoxic effects of perfluorooctanoic acid in
      human cells that could be of special relevance for use in comparative in vitro-in
      vivo studies. Moreover, our findings highlight the importance of considering both
      the immediate and long-lasting or delayed cytotoxic responses caused by chemical
      exposure, to ensure the accurate identification of toxicity in cell-based
      systems.

PMID- 30217484
TI  - Distinguishing between endocrine disruption and non-specific effects on endocrine
      systems.
AB  - The endocrine system is responsible for growth, development, maintaining
      homeostasis and for the control of many physiological processes. Due to the
      integral nature of its signaling pathways, it can be difficult to distinguish
      endocrine-mediated adverse effects from transient fluctuations,
      adaptive/compensatory responses, or adverse effects on the endocrine system that
      are caused by mechanisms outside the endocrine system. This is particularly true
      in toxicological studies that require generation of effects through the use of
      Maximum Tolerated Doses (or Concentrations). Endocrine-mediated adverse effects
      are those that occur as a consequence of the interaction of a chemical with a
      specific molecular component of the endocrine system, for example, a hormone
      receptor. Non-endocrine-mediated adverse effects on the endocrine system are
      those that occur by other mechanisms. For example, systemic toxicity, which
      perturbs homeostasis and affects the general well-being of an organism, can
      affect endocrine signaling. Some organs/tissues can be affected by both endocrine
      and non-endocrine signals, which must be distinguished. This paper examines in
      vitro and in vivo endocrine endpoints that can be altered by non-endocrine
      processes. It recommends an evaluation of these issues in the assessment of
      effects for the determination of endocrine disrupting properties of chemicals.
      This underscores the importance of using a formal weight of evidence (WoE)
      process to evaluate potential endocrine activity.

PMID- 30217485
TI  - Validation of the Acoustic Voice Quality Index Version 03.01 and Acoustic
      Breathiness Index in German.
AB  - OBJECTIVE: The aim of this study was to validate the acoustic voice quality index
      (AVQI) version 03.01 and the acoustic breathiness index (ABI) in the German
      language. METHODS: Concatenated voice samples of continuous speech (cs) and
      sustained vowel (sv) [a:] from 175 subjects with dysphonia and 43 vocally healthy
      subjects were perceptually judged for overall voice quality and breathiness
      severity. First, to reach a higher level of ecological validity, the proportions
      of cs and sv were equalized regarding the time length. Second, concurrent
      validity and diagnostic accuracy were statistically verified using the Spearman
      rank-order correlation coefficient (rs) and several estimates of the receiver
      operating characteristics, likelihood ratio, and Youden index. RESULTS: A
      moderate reliability of overall voice quality and breathiness severity from three
      experts were found. It was found that 27 syllables as standardization of the cs
      part, which represents 3 seconds of voiced cs, allows the equalization of both
      speech tasks. A strong correlation was revealed between AVQI and overall voice
      quality (rs = 0.86, P < 0.01), and ABI and perceived breathiness severity (rs =
      0.85, P < 0.01). Additionally, the best diagnostic outcome for AVQI and ABI was
      identified at a threshold of 1.85 (sensitivity of 72 % and specificity of 90 %)
      and 3.42 (sensitivity of 72 % and specificity of 95 %), respectively. CONCLUSION:
      AVQI and ABI showed in the German language valid and robust results to quantify
      abnormal voice qualities regarding overall voice quality and breathiness
      severity.

PMID- 30217486
TI  - Non invasive mechanical ventilation in DM1: The strong correlation between lung
      function, neurological-cognitive function and CTG repeats.

PMID- 30217487
TI  - Myoglobinuria in two patients with Duchenne muscular dystrophy after treatment
      with zoledronate: a case-report and call for caution.
AB  - Rhabdomyolysis with myoglobinuria is a recognized complication of
      dystrophinopathies. It can be triggered by infections, exercise or volatile
      anesthetics. To our knowledge, it has never been reported in boys with Duchenne
      muscular dystrophy (DMD) after the administration of bisphosphonates. We report
      two patients with DMD who presented an apparent transient rhabdomyolysis with
      myoglobinuria after zoledronate administration. Possible mechanisms could involve
      hypophosphatemia, a known dose-dependent side effect of bisphosphonates, and/or
      direct myotoxicity of biphosphonates. Physicians and families should be aware of
      rhabdomyolysis with myoglobinuria as a potential uncommon side effect of
      bisphosphonates in DMD, in particular of zoledronate.

PMID- 30217488
TI  - Erratum to "NDRG1 disruption alleviates cisplatin/sodiumlycididazole-induced DNA
      damage response and apoptosis in ERCC1-defective lung cancer cells" [Int. J.
      Biochem. Cell Biol. 100 (2018) 54-64].

PMID- 30217489
TI  - A brief report of transformation from Non-small cell to small cell lung cancer:
      Molecular and therapeutic characteristics.
AB  - : Histological transformation from Non-small cell lung cancer (NSCLC) to SCLC is
      a mechanism of resistance in EGFR-mutant tumors but is also occasionally observed
      in non-mutated NSCLC. PATIENTS AND METHODS: We performed a multicenter
      retrospective collection of cases presenting between 2005 and 2017. The
      objectives were to analyse survival data and to define epidemiological, clinical,
      treatment and histo-molecular characteristics at both the time of diagnosis of
      NSCLC and of SCLC. RESULTS: Forty-eight EGFR-mutant NSCLC and 13 non-EGFR-mutant
      cases were registered. Most EGFR-mutant tumors retained the same EGFR mutation
      after transformation. The median time to SCLC transformation was shorter in the
      EGFR-mutant group than in non-EFGR mutants (16 months versus 26 months (p=
      0.01)). Both tumors were responsive to platinum etoposide regimens (45% partial
      response for the EGFR-mutant group versus 40% for non-EFGR mutants). The median
      overall survival were respectively 28 months in the EGFR-mutant group versus 37
      months in the non-EFGR-mutant group. After transformation the median overall
      survival was 9 months in the non-EGFR-mutant group versus 10 months. CONCLUSION:
      Transformation into SCLC seems to occur more quickly in EGFR mutated tumors,
      however once the tumor is transformed its survival and response to treatment
      seems comparable to that of classical SCLC.

PMID- 30217490
TI  - Impact of Lymph Node Dissection on Thymic Malignancies: Multi-Institutional
      Propensity Score Matched Analysis.
AB  - INTRODUCTION: Surgical resection is a standard treatment for thymic malignancies.
      However, prognostic significance of nodal metastases and lymph node dissection
      remains unclear. The aim of this study is to determine prognostic significance of
      nodal metastases and the role of lymph node dissection (LND) in thymic
      malignancies. METHODS: Between 2000 and 2013, 1597 patients who underwent
      thymectomy due to thymic malignancy were included. Predictive factors for nodal
      metastasis and prognostic significance of LND were evaluated. Patients were
      divided into two groups: (1) LND+ group, with intentional LND (446 patients,
      27.9%); and (2) LND- group, without intentional LND (1151 patients, 72.1%).
      Propensity score matching was performed between the two groups. RESULTS: Lymph
      node metastasis was identified in 20 (6.7%) of 298 patients with thymoma and 47
      (31.7%) of 148 patients with thymic carcinoma. In multivariable analysis, thymic
      carcinoma (hazard ratio: 19.2, p < 0.001) and tumor size (hazard ratio: 1.09, p =
      0.02) were significant predictive factors for lymph node metastasis. The 10-year
      freedom from recurrence rate of pN1 and pN2 was significantly worse than that of
      pN0 (p < 0.001). LND did not increase operative mortality or complication. There
      was no significant difference in 10-year freedom from recurrence rate between
      LND+ and LND- groups (82.4% versus 80.9%, p = 0.46 in thymoma; 45.7% versus
      44.0%, p = 0.42 in thymic carcinoma). CONCLUSIONS: Lymph node metastasis was a
      significant prognostic factor in thymic malignancies. Although LND did not
      improve long-term outcomes in thymic malignancies, LND played a role in accurate
      staging, and improved prediction of prognosis.

PMID- 30217491
TI  - Lengthy Progression-Free Survival and Intracranial Activity of Cabozantinib in
      Patients with Crizotinib and Ceritinib-Resistant ROS1-Positive Non-Small Cell
      Lung Cancer.

PMID- 30217492
TI  - Atezolizumab Treatment Beyond Progression in Advanced NSCLC: Results From the
      Randomized, Phase III OAK Study.
AB  - INTRODUCTION: Cancer immunotherapy may alter tumor biology such that treatment
      effects can extend beyond radiographic progression. In the randomized, phase III
      OAK study of atezolizumab (anti-programmed death-ligand 1) versus docetaxel in
      advanced NSCLC, overall survival (OS) benefit with atezolizumab was observed in
      the overall patient population, without improvement in objective response rate
      (ORR) or progression-free survival (PFS). We examine the benefit-risk of
      atezolizumab treatment beyond progression (TBP). METHODS: Eight hundred fifty
      patients included in the OAK primary efficacy analysis were evaluated.
      Atezolizumab was continued until loss of clinical benefit. Docetaxel was
      administered until Response Evaluation Criteria in Solid Tumors version 1.1
      (RECIST v1.1) disease progression (PD)/unacceptable toxicity; no crossover to
      atezolizumab was allowed. ORR, PFS, post-PD OS, target lesion change, and safety
      were evaluated. RESULTS: In atezolizumab-arm patients, ORR was 16% versus 14% and
      median PFS was 4.2 versus 2.8 months per immune-modified RECIST versus RECIST
      v1.1. The median post-PD OS was 12.7 months (95% confidence interval [CI]: 9.3
      14.9) in 168 atezolizumab-arm patients continuing TBP, 8.8 months (95% CI: 6.0
      12.1) in 94 patients switching to nonprotocol therapy, and 2.2 months (95% CI:
      1.9-3.4) in 70 patients receiving no further therapy. Of the atezolizumab TBP
      patients, 7% achieved a post-progression response in target lesions and 49% had
      stable target lesions. Atezolizumab TBP was not associated with increased safety
      risks. CONCLUSIONS: Within the limitations of this retrospective analysis, the
      post-PD efficacy and safety data from OAK are consistent with a positive benefit
      risk profile of atezolizumab TBP in patients performing well clinically at the
      time of PD.

PMID- 30217493
TI  - Methylation status of ORMDL3 regulates cytokine production and p-ERK/MMP9 pathway
      expression.
AB  - Orosomucoid like-3 (ORMDL3) has been identified to be associated with the
      development of asthma according to previous studies. However, the definite role
      of ORMDL3 in the pathogenesis of asthma remains unclear. In this study, we found
      ORMDL3 was highly expressed in PBMC specimens from childhood asthma patients.
      Cytokines production and p-ERK/MMP-9 pathway expression was also increased in
      childhood asthma patients compared with controls. In addition, ORMDL3
      overexpression induced IL-6 and IL-8 release and activated p-ERK/MMP-9 pathway in
      vitro. Increased ORMDL3 expression was observed after treated with 5-Aza-CdR. 5
      Aza-CdR decreased the percentage of the CpG island in the ORMDL3 promoter region
      and increased its promoter activity. In addition, 5-Aza-CdR significantly
      increased IL-6 and IL-8 levels in NHBE cells while there was no obvious
      alteration after knocking down ORMDL3. Knockdown of ORMDL3 also significantly
      decreased the expression of p-ERK/MMP-9 pathway in the presence or absence of 5
      Aza-CdR. In conclusion, our study provided novel evidence for the association
      between ORMDL3 and asthma-associated cytokines. Moreover, DNA methylation plays
      an important role in ORMDL3-mediated increased IL-6 and IL-8 levels and p-ERK/MMP
      9 pathway expression.

PMID- 30217494
TI  - Relationship between diastasis of the rectus abdominis muscle (DRAM) and
      musculoskeletal dysfunctions, pain and quality of life: a systematic review.
AB  - BACKGROUND: Diastasis of the rectus abdominis muscle (DRAM) is common during and
      after pregnancy. OBJECTIVES: To determine the association between: the presence
      of DRAM and low back pain, lumbo-pelvic pain, incontinence, pelvic organ
      prolapse, abdominal muscle performance or health-related quality of life; and
      between DRAM width and severity of these outcomes. DATA SOURCES: Six electronic
      databases (EMBASE, Medline, CINAHL, PUBMED, AMED and PEDro). STUDY SELECTION:
      Included studies of all designs with adults with DRAM that assessed low back
      pain, lumbo-pelvic pain incontinence, pelvic organ prolapse, abdominal
      performance or health-related quality of life. STUDY APPRAISAL & SYNTHESIS
      METHODS: Methodological quality was assessed using the Effective Public Health
      Practice Project tool. A narrative summary was completed for DRAM presence and
      presence of the various musculoskeletal dysfunctions, and DRAM width and the
      severity of these dysfunctions. RESULTS: Twelve studies involving 2242
      participants were included. There was no significant association between the
      presence of DRAM and lumbo-pelvic pain or incontinence. There was a small
      association between the presence of DRAM and pelvic organ prolapse. DRAM width
      may be associated with health-related quality of life, abdominal muscle strength
      and severity of low back pain. LIMITATIONS: Quality of studies was weak. There
      was variability in the methods used to assess DRAM. CONCLUSION: There is weak
      evidence that DRAM presence may be associated with pelvic organ prolapse, and
      DRAM severity with impaired health-related quality of life, impaired abdominal
      muscle strength and low back pain severity. Systematic Review Registration
      Number: PROSPERO CRD42017058089.

PMID- 30217495
TI  - Structurally- and dynamically-driven allostery of the chymotrypsin-like proteases
      of SARS, Dengue and Zika viruses.
AB  - Coronavirus 3C-like and Flavivirus NS2B-NS3 proteases utilize the chymotrypsin
      fold to harbor their catalytic machineries but also contain additional domains/co
      factors. Over the past decade, we aimed to decipher how the extra domains/co
      factors mediate the catalytic machineries of SARS 3C-like, Dengue and Zika NS2B
      NS3 proteases by characterizing their folding, structures, dynamics and
      inhibition with NMR, X-ray crystallography and MD simulations, and the results
      revealed: 1) the chymotrypsin fold of the SARS 3C-like protease can independently
      fold, while, by contrast, those of Dengue and Zika proteases lack the intrinsic
      capacity to fold without co-factors. 2) Mutations on the extra domain of SARS 3C
      like protease can transform the active catalytic machinery into the inactive
      collapsed state by structurally-driven allostery. 3) Amazingly, even without
      detectable structural changes, mutations on the extra domain are sufficient to
      either inactivate or enhance the catalytic machinery of SARS 3C-like protease by
      dynamically-driven allostery. 4) Global networks of correlated motions have been
      identified: for SARS 3C-like protease, N214A inactivates the catalytic machinery
      by decoupling the network, while STI/A and STIF/A enhance by altering the
      patterns of the network. The global networks of Dengue and Zika proteases are
      coordinated by their NS2B-cofactors. 5) Natural products were identified to
      allosterically inhibit Zika and Dengue proteases through binding a pocket on the
      back of the active site. Therefore, by introducing extra domains/cofactors,
      nature develops diverse strategies to regulate the catalytic machinery embedded
      on the chymotrypsin fold through folding, structurally- and dynamically-driven
      allostery, all of which might be exploited to develop antiviral drugs.

PMID- 30217496
TI  - Parvimonas micra bacteremia following endoscopic retrograde
      cholangiopancreatography: A new route of infection.
AB  - Parvimonas micra is an anaerobic, Gram-positive coccus belonging to oral,
      gastrointestinal and genital flora, rarely causing infections in humans. It was
      mainly deemed to cause bacteremia, septic bone and cerebral infections in
      patients which have undergone dental procedures or with suboptimal dental
      hygiene. We report the first case of Parvimonas micra bacteremia following
      endoscopic retrograde colangiopancreatography performed due to
      choledocholithiasis in a patient with good oral health. Identification of P.
      micra was finally performed by Matrix-assisted laser desorption ionization-time
      of flight mass spectrometry (VITEK MS system, bioMerieux, Marcy l'Etoile,
      France). All cases reported in english language of Parvimonas micra infections
      after medical procedure are reviewed in order to alert clinicians about new
      possible routes of infection of this emerging pathogen.

PMID- 30217497
TI  - Changes of cardiac function in diabetic dogs.
AB  - OBJECTIVE: This study aimed to evaluate cardiac function and compare the
      concentration of cardiac biomarkers including cardiac troponin I (cTnI), galectin
      3 (Gal-3), and N-terminal pro B-type natriuretic peptides (NT-proBNP) in diabetic
      and control dogs. ANIMALS: Thirty-nine dogs were included. The diabetic and
      control groups consisted of 19 and 20 dogs, respectively. METHODS: Plasma cTnI,
      Gal-3, and NT-proBNP concentrations were measured in the diabetic and control
      groups. Echocardiography was performed in all dogs to evaluate cardiac structure
      and function. Echocardiographic values and cardiac biomarker concentrations
      between the two groups were compared with the Mann-Whitney U test. The p-value <
      0.05 was considered statistical significance. RESULTS: No evidence of cardiac
      structural changes was detected in diabetic dogs on two-dimensional
      echocardiography. The echocardiographic values of diabetic and control dogs were
      within reference intervals. Echocardiographic changes indicating diastolic
      dysfunction assessed by spectral flow Doppler echocardiography and tissue Doppler
      imaging were found in diabetic dogs (42.10%) compared with control dogs (10.00%;
      p = 0.022). Diabetic dogs with durations of diabetes mellitus > 1 year had an
      increased left ventricular wall thickness and echocardiographic changes
      suggesting diastolic dysfunction compared with those with duration of diabetes
      mellitus < 1 year. No evidence of systolic dysfunction was detected in diabetic
      dogs. No significant difference in plasma cTnI, Gal-3, and NT-proBNP
      concentrations was found between the two groups. CONCLUSIONS: Echocardiographic
      changes suggested that left ventricular diastolic dysfunction was detected in
      diabetic dogs without changes in the concentration of cardiac biomarkers
      including cTnI, Gal-3, and NT-proBNP compared with the age- and breed-matched
      control dogs.

PMID- 30217498
TI  - Successful transcatheter retrieval of embolized Amplatz Canine Duct Occluders in
      two dogs.
AB  - Transcatheter occlusion of patent ductus arteriosus (PDA) using an Amplatz(r)
      Canine Duct Occluder (ACDO) is routinely performed in dogs. Pulmonary
      embolization of the device is a rarely reported complication of this procedure.
      We report here the first two cases of successful transcatheter retrieval of an
      embolized ACDO. An 8-month-old, 21-kg, German shepherd (case 1) was referred for
      pulmonary edema secondary to a large PDA with left-to-right shunting. After
      medical stabilization, an emergency procedure for PDA closure was recommended. An
      8-mm ACDO was deployed under general anesthesia. The device was released after
      confirming its stability with a gentle tug test but migrated into the pulmonary
      trunk. A 10-mm ACDO was subsequently successfully deployed and released. Vascular
      access was then obtained from the right jugular vein so that a vascular snare
      could be used to capture the ACDO waist and pull it back toward the right
      ventricle and then the right atrium. It was then removed through the jugular
      vein. The dog recovered uneventfully and was discharged after confirmation of
      complete ductal occlusion. The same complication occurred in a second case (case
      2, asymptomatic 6-month-old, 7.9-kg, cocker spaniel), and a similar procedure was
      used to successfully retrieve the embolized device. Both dogs are still doing
      well 9 and 21 months, respectively, after the procedure. These cases illustrate
      that transcatheter retrieval of ACDO devices embolized in the pulmonary artery
      using vascular snares is technically feasible in the dog.

PMID- 30217499
TI  - Validation of a quick and low-cost DNA extraction protocol applicable to long
      stored blood samples.

PMID- 30217500
TI  - Isothermal DNA amplification combined with lateral flow dipsticks for detection
      of biothreat agents.
AB  - The recently developed methods of nucleic acids isothermal amplification are
      promising tools for point-of-care diagnostics and in the field detection of
      pathogenic microorganisms. However, application of these methods outside a
      laboratory faces some challenges such as the rapid and sensitive detection of
      amplified products and the absence of cross-reactivity with genetically related
      microorganisms. In the presented study we compared three methods of isothermal
      DNA amplification loop-mediated isothermal amplification (LAMP), recombinase
      polymerase amplification (RPA) and thermophilic helicase-dependent isothermal DNA
      amplification (tHDA), for detection of highly dangerous pathogens, such as
      Bacillus anthracis, Francisella tularensis and Yersinia pestis, and combined them
      with lateral flow dipsticks for the rapid visualization of amplified products. We
      observed low specificity of the three methods for B. antharcis, medium for Y.
      pestis and high for F. tularensis detection. Sensitivity and the detection limit
      were high and comparable for all the methods. We concluded that the lateral flow
      dipsticks have been a very useful tool for product detection of the isothermal
      amplification methods and enable reading the results without the use of any
      equipment. However, our results showed that the use of isothermal amplification
      methods is strongly related to the risk of false positive results.

PMID- 30217501
TI  - Don't turn-off the brain.

PMID- 30217502
TI  - Central action of CART induces neuronal activation in the paraventricular and
      dorsomedial hypothalamus of diet-induced obese and lean mice.
AB  - The cocaine- and amphetamine-regulated transcript (CART) is a peptide commonly
      studied in the feeding behavior, but it exerts an important role in the autonomic
      and cardiovascular control as well. It is known that exogenous administration of
      CART in the central nervous system can elicit increase in blood pressure of both
      conscious and anesthetized rodents, but little is known whether these central
      effects might differ between lean and obese animals. We have recently shown that
      diet-induced obese mice that developed hypertension presented an upregulation of
      CART levels in the dorsomedial nucleus of hypothalamus, while obese normotensive
      ones had not. Herein we investigate whether the central action of CART could
      activate differently the hypothalamic nuclei of diet-induced obese mice compared
      to the lean counterparts by using Fos protein expression, C57BL/6 mice were
      randomly assigned to two cohorts, one fed with a high-fat diet for 8 weeks
      (obese), and the other fed with regular rodent chow (lean). Both groups received
      an ICV injection of CART at the dose of 400MUM, 1 mM or vehicle. Subsequently,
      the brains were processed for Fos protein immunohistochemical in order to
      identify hypothalamic neuronal activation. Significantly greater numbers of Fos
      positive neurons were observed in the PVN and DMH of obese mice that received
      CART 1 mM, when compared to the lean control. These results indicate that the
      central action of CART induces neuronal activation in the hypothalamic nuclei of
      obese and lean mice, and this could be relevant to the different autonomic and
      cardiovascular adjustments that an organism exposed to different diet and
      metabolic condition.

PMID- 30217503
TI  - First gender, then attractiveness: Indications of gender-specific attractiveness
      processing via ERP onsets.
AB  - We followed an ERP-based approach to gain knowledge on the dependence and
      temporal order of two essential processes of face perception: attractiveness and
      gender. By combining a dual-choice task with a go/nogo-paradigm focusing on the
      LRP and N200-effect, we could estimate the processing times and onsets of both
      types of face processing. The analyses of the LRP revealed that gender aspects
      were processed much earlier than attractiveness. Whereas gender was already
      analysed 243.9 ms post-stimulus onset, attractiveness came into play 58.6 ms
      later, i.e. after a post-stimulus onset delay of 302.5 ms. This resulting pattern
      was mirrored by the analyses of the N200-effect, an effect available mainly
      frontally which is supposed to correlate with the inhibition of inappropriate
      responses. Taking the onset of the N200 effect as an estimator for the moment at
      which information has been processed sufficiently for task decision, we could
      trace the N200 effect at 152.0 ms for go/nogo-decision on gender, while not as
      early as 206.7 ms on attractiveness. In sum, processing of facial attractiveness
      seems to be based on gender-specific aesthetic pre-processing, for instance via
      activating gender-specific attractiveness prototypes which show focused
      processing of certain facial aspects.

PMID- 30217504
TI  - Mesenchymal Stem Cell Treatment Attenuates Liver and Lung Inflammation after
      Ethanol Intoxication and Burn Injury.
AB  - Cutaneous burn injury is one of the most devastating injuries one can obtain with
      tissue damage extending beyond the skin wound to distal organs, including the
      gastrointestinal tract, liver, and lungs. Multiple organ failure is a leading
      cause of death after burn injury resulting in excessive systemic and localized
      inflammation directly contributing to end organ damage. We postulated that the
      gut-liver-lung inflammatory axis underscores multiple organ failure in the
      context of burn injury and is hyper-activated when ethanol intoxication precedes
      burn. Mesenchymal stem cells (MSCs) are regenerative and anti-inflammatory and
      MSC treatment has been shown to be beneficial in several immune disorders and
      injury models. Our objective was to determine whether intravenous infusion of
      exogenous bone marrow-derived MSCs could reduce post-burn and intoxication
      pulmonary, hepatic, and systemic inflammation. Vehicle or ethanol (1.6 g/kg)
      treated mice were subjected to sham or 15% total body surface area scald burn.
      One hour post-injury, mice were given 5x105 CFSE-labeled MSCs or phosphate
      buffered saline intravenously (i.v.) and euthanized 24h later. We assessed
      circulating biomarkers of inflammation and liver damage, measured cytokine and
      chemokine production and quantified apoptosis in lung and liver tissue. Compared
      to intoxicated and burned mice, those treated with MSCs had less cellularity,
      limited apoptosis, and a slight reduction in the pro-inflammatory cytokine
      interleukin-6 (IL-6) and the neutrophil chemokine, KC (CXCL1) in lung tissue.
      MSCs treatment had more dramatic anti-inflammatory effects on systemic and
      hepatic inflammation, as serum IL-6 levels were diminished by 43%, il6 and kc
      expression in liver tissue were markedly reduced, as were biomarkers of liver
      damage, aspartate transaminase (AST) and alanine transaminase (AST), compared
      with intoxicated and burned mice. Taken together, our results suggest intravenous
      MSCs treatment can diminish systemic inflammation, lessen hepatic damage, and
      decrease liver and lung apoptosis and inflammation, indicating MSCs as a novel
      therapy for restoring homeostasis of multiple organ systems in intoxicated burn
      patients.

PMID- 30217505
TI  - Transcriptomic analysis of immune-related genes in the lipopolysaccharide
      stimulated hepatopancreas of the mudflat crab Helice tientsinensis.
AB  - The mudflat crab Helice tientsinensis is one of the most economically important
      aquaculture species in China. Nevertheless, it is susceptible to various diseases
      caused by viruses, bacteria and rickettsia-like organisms. A better understanding
      of the immune system and genes related to the responses to bacterial and viral
      infection is required. Herein, the hepatopancreas transcriptome of H.
      tientsinensis was analyzed by comparing control and lipopolysaccharide (LPS)
      stimulated RNA-Seq data, yielding 91,885,038 bp and 13.78 Gb of clean reads.
      Following assembly and annotation, 93,207 unigenes with an average length of 883
      bp were identified, of which 31,674 and 13,700 were annotated in Gene Ontology
      (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively.
      Following LPS, 4845 differentially expressed genes (DEGs) were identified, of
      which 2491 and 2354 were up- and down-regulated, respectively. To further
      investigate immune-related DEGs, KEGG enrichment analysis identified immune
      response pathways, most notably the peroxisome and Toll-like receptor signaling
      pathways. Quantitative real time-PCR (qRT-PCR) confirmed the up-regulation of a
      random selection of DEGs. This systematic transcriptomic analysis of the innate
      immune pathway in H. tientsinensis expands our understanding of the immune system
      in crabs.

PMID- 30217506
TI  - Independent and simultaneous effect of crustacean hyperglycemic hormone and
      dopamine on the hemocyte intracellular signaling pathways and immune responses in
      white shrimp Litopenaeus vannamei.
AB  - Immune responses and intracellular signaling pathways were examined after
      hemolymph of Litopenaeus vannamei being incubated in Crustacean hyperglycemic
      hormone (CHH), dopamine (DA) and DA antagonist (Y). The results showed that the
      effect CHH and CHH + DA + Y on viability of hemocytes were no significant changes
      compared to the control group. However, in DA, DA + Y and CHH + DA groups, the
      viability of hemocytes decreased significantly. The phagocytic activity and the
      antibacterial activity of CHH group were increased significantly within 12h.
      Whereas the CHH + DA, DA were significantly lower than the control. PO in
      haemolymph was up-regulated after CHH and DA incubation. The proPO has the
      opposite change in all groups. In addition, DA + Y, CHH + DA + Y has a similar
      trend with the DA and CHH respectively. Furthermore, a significant increase of
      cAMP, CaM and cGMP were found in treatment groups except for the CaM
      concentration of the CHH group and the cGMP concentration of DA group. There is
      no significant change observed in the CHH group about CaM concentration. Whereas
      the cGMP of DA group decreased within 12h. The results suggest that DA could
      depress the immune responses by cAMP-, CaM-pathways. However, the CHH is on the
      contrary, which transduced the signals from cAMP, cGMP to PKA, PKC and PKG to
      enhance the immune response parameters.

PMID- 30217507
TI  - Oral immunization with a recombinant Lactobacillus expressing CK6 fused with VP2
      protein against IPNV in rainbow trout (Oncorhynchus mykiss).
AB  - Infectious pancreatic necrosis virus (IPNV) infects wild and cultured salmonid
      fish causing high mortality with serious economic losses to salmonid aquaculture.
      Ideally, the method of oral immunization should prevent the infection of rainbow
      trout juveniles with IPNV. In the present study, genetically engineered
      Lactobacillus casei 393 pPG-612-VP2/L. casei 393 and pPG-612-CK6-VP2/L. casei 393
      constitutively expressing VP2 protein of IPNV were constructed. The recombinant
      strains pPG-612-CK6-VP2/L. casei 393 and pPG-612-VP2/L. casei 393 were orally
      administrated to juvenile rainbow trouts, and significant titers of IgM and IgT
      of pPG-612-CK6-VP2/L. casei 393 were observed. The results demonstrate that the
      recombinants could elicit both local mucosal and systemic immune responses. The
      proliferation of spleen lymphocytes in trouts immunized with pPG-612-CK6-VP2/L.
      casei 393 showed that the recombinant strain could induce a strong cellular
      immune response. The IL-1beta, IL-8, CK6, MHC-II, Mx, beta-defensin, and TNF
      1alpha levels in the spleen and gut suggest that the target molecular chemokine
      has the ability to attract relevant immune cells to participate in the
      inflammatory response and enhance the function of the innate immune response.
      Additionally, the pPG-612-CK6-VP2/L. casei 393 induced the expression of
      cytokines, which have the effect of promoting inflammation to drive the
      differentiation of macrophages and clear target cells. After challenging with
      IPNV, the reduction in viral load caused by pPG-612-CK6-VP2/L. casei 393 was
      significantly higher than that of the other groups. Thus, the recombinant pPG-612
      CK6-VP2/L. casei 393 is a promising candidate for the development of an oral
      vaccine against IPNV.

PMID- 30217508
TI  - Synergistic effects of dietary supplementation of Bacillus subtilis WB60 and
      mannanoligosaccharide (MOS) on growth performance, immunity and disease
      resistance in Japanese eel, Anguilla japonica.
AB  - This study evaluated the synergistic effects of dietary Bacillus subtilis WB60
      and mannanoligosaccharide (MOS) in juvenile Japanese eel, Anguilla japonica.
      Seven treatment diets were formulated to contain three different levels of B.
      subtilis (0.0, 0.5, and 1.0 * 107 CFU/g diet denoted as BS0, BS0.5, and BS1,
      respectively) with two MOS levels (0 and 5 g/kg diet denoted as M0 and M5,
      respectively), and one diet with oxytetracycline (OTC) at 5 g/kg diet. Each diet
      (BS0M0 (CON), BS0M5, BS0.5M0, BS0.5M5, BS1M0, BS1M5, and OTC) was fed to
      triplicate groups of 20 fish averaging 9.00 +/- 0.11 g (mean +/- SD) for eight
      weeks. Average weight gain, feed efficiency, specific growth rate and protein
      efficiency ratio of fish fed the BS0.5M5 and BS1M5 diets were significantly
      higher than those of fish fed CON, BS0.5M0 and OTC diets (P < 0.05). Significant
      increases in the nonspecific enzymatic activities (e.g., lysozyme and
      myeloperoxidase) were detected from fish fed the BS0.5M5, BS1M5, and OTC diets
      compared to the CON, BS0.5M0, and BS0M5 diets (P < 0.05). Whereas, immunoglobulin
      M expressions were recorded significantly higher for fish fed the BS0.5M5 and
      BS1M5 diets compared to those of fish fed the other diets (P < 0.05). Also, heat
      shock protein 70 mRNA levels of fish fed BS0.5M5 and BS1M5 diets were
      significantly higher than those of fish fed the CON diet (P < 0.05). Histological
      observations of the intestinal morphology showed healthier gut for fish fed
      BS0.5M5 and BS1M5 diets than those fed CON, BS0M5, and OTC diets. Additionally,
      resistance to bacterial challenge with Vibrio anguillarum was recorded
      significantly lower for fish fed the CON diet than those fed other diets (P >
      0.05). Therefore, the results for growth performance, non-specific immune
      responses, intestinal morphology, and disease resistance demonstrated that
      supplementation of B. subtilis at 0.5 * 107 CFU/g diet and mannanoligosaccharide
      at 5 g/kg diet could have beneficial synergistic effects in Japanese eel. The
      isolated probiotic from eel and the selected prebiotic could lead to the
      development of a specific and potential synbiotic in Japanese eel aquaculture.

PMID- 30217509
TI  - Bcl2L12 mediates effects of protease-activated receptor-2 on the pathogenesis of
      Th2-dominated responses of patients with ulcerative colitis.
AB  - The immune dysregulation plays an important role in the pathogenesis of
      ulcerative colitis (UC). Bcl2 like protein-12 (Bcl2L12) and mast cells are
      involved in immune dysregulation of UC. This study aims to elucidate the role of
      Bcl2L12 in the contribution to the pathogenesis of T helper (Th)2-biased
      inflammation in UC patients. The results showed that Bcl2L12 was expressed by
      peripheral CD4+ T cells that was associated with Th2 polarization in UC patients.
      Bcl2L12 mediated the protease-activated receptor-2 (PAR2)-induced IL-4 expression
      in CD4+ cells. Activation of PAR2 increased expression of Bcl2L12 in CD4+ T
      cells. Bcl2L12 mRNA decayed spontaneously in CD4+ T cells after separated from UC
      patients which was prevented by activating PAR2. Bcl2L12 mediated the binding
      between GATA3 and the Il4 promoter in CD4+ T cells. Mice with Bcl2L12 deficiency
      failed to induce Th2-biased inflammation in the colon mucosa. We conclude that
      CD4+ T cells from UC patients expressed high levels of Bcl2L12; the latter plays
      an important role in the development of Th2-biased inflammation in the intestine.
      Bcl2L12 may be a novel therapeutic target in the treatment of Th2-biased
      inflammation.

PMID- 30217510
TI  - Activation of calcium-sensing receptor by allosteric agonists cinacalcet and AC
      265347 abolishes the 1,25(OH)2D3-induced Ca2+ transport: Evidence that explains
      how the intestine prevents excessive Ca2+ absorption.
AB  - Long-term high-calcium intake and intestinal calcium hyperabsorption are
      hazardous to the body. It is hypothesized that enterocytes possess mechanisms for
      preventing superfluous calcium absorption, including secretion of negative
      regulators of calcium absorption and utilization of calcium-sensing receptor
      (CaSR) to detect luminal calcium. Herein, Caco-2 monolayers were treated with
      high doses of 1,25(OH)2D3 to induce calcium hyperabsorption or directly exposed
      to high apical calcium. The expression of counterregulatory factor of calcium
      absorption, fibroblast growth factor (FGF)-23, was also investigated in the
      intestine of lactating rats, which physiologically exhibit calcium
      hyperabsorption. We found that FGF-23 expression was enhanced in all intestinal
      segments of lactating rats. In Caco-2 monolayers, high apical calcium and
      1,25(OH)2D3 induced FGF-23 secretion into culture media. FGF-23 antagonized
      1,25(OH)2D3-induced calcium transport and led to a significant, but small, change
      in paracellular permeability. Furthermore, high-dose 1,25(OH)2D3 upregulated FGF
      23 expression, which was prevented by CaSR inhibitors. Activation of apical CaSR
      by cinacalcet and AC-265347 abolished 1,25(OH)2D3-induced calcium transport in a
      dose-dependent manner. In conclusion, the intestinal FGF-23 expression was
      upregulated in conditions with calcium hyperabsorption, presumably to help
      protect against excessive calcium absorption, while CaSR probably monitored
      calcium in the lumen and induced FGF-23 production for preventing superfluous
      calcium uptake.

PMID- 30217511
TI  - Uncoupling proteins: Martin Klingenberg's contributions for 40 years.
AB  - The uncoupling protein (UCP1) is a proton (H+) transporter in the mitochondrial
      inner membrane. By dissipating the electrochemical H+ gradient, UCP1 uncouples
      respiration from ATP synthesis, which drives an increase in substrate oxidation
      via the TCA cycle flux that generates more heat. The mitochondrial uncoupling
      mediated non-shivering thermogenesis in brown adipose tissue is vital primarily
      to mammals, such as rodents and new-born humans, but more recently additional
      functions in adult humans have been described. UCP1 is regulated by beta
      adrenergic receptors through the sympathetic nervous system and at the molecular
      activity level by nucleotides and fatty acid to meet thermogenesis needs. The
      discovery of novel UCP homologs has greatly contributed to the understanding of
      human diseases, such as obesity and diabetes. In this article, we review the
      progress made towards the molecular mechanism and function of the UCPs, in
      particular focusing on the influential contributions from Martin Klingenberg's
      laboratory. Because all members of the UCP family are potentially promising drug
      targets, we also present and discuss possible approaches and methods for UCP
      related drug discovery.

PMID- 30217512
TI  - Long-term motor and sensory outcomes after surgery for the nonaccommodative
      component of partially refractive accommodative esotropia.
AB  - PURPOSE: To report long-term motor and sensory outcomes after surgery for the
      nonaccommodative component of partially refractive accommodative esotropia
      (PRAET). METHODS: The medical records of consecutive patients <=11 years old
      operated for the nonaccommodative component of PRAET and followed postoperatively
      for at least 10 years were retrospectively reviewed. RESULTS: A total of 47
      patients were included (median age, 3.0 years). The mean postoperative follow-up
      was 12.15 +/- 2.05 years (range, 10.00-17.50 years). Overall, 23 patients (49%)
      had surgical success; 10 (21%), decompensation; and 7 (15%), esotropia with a
      high ratio of accommodative convergence to accommodation (AC/A) or consecutive
      exotropia. The median age at surgery, mean cycloplegic refraction, median near
      and distance deviation, presence of binocular vision, and amblyopia did not
      predict decompensation, a high AC/A ratio esotropia, and consecutive exotropia.
      Eight patients (18%) achieved stereopsis. Patients with an older age at onset
      (2.87 +/- 1.31 years) and a shorter duration of strabismus (<=4 years) achieved
      better stereopsis. CONCLUSIONS: Nearly half of our patients with PRAET achieved a
      successful ocular alignment after surgery for the nonaccommodative component.
      Some developed decompensation, a high AC/A ratio esotropia, or consecutive
      exotropia. Few patients achieved stereopsis. Older age at onset and a shorter
      duration of strabismus predicted a better stereopsis outcome.

PMID- 30217514
TI  - The co-colonization prevalence of Pseudomonas aeruginosa and Aspergillus
      fumigatus in cystic fibrosis: A systematic review and meta-analysis.
AB  - PURPOSE: The co-colonization prevalence of P. aeruginosa and A. fumigatus in
      cystic fibrosis (CF) has been inconsistently reported. The purpose of this
      systematic review and meta-analysis was to estimate the overall co-colonization
      prevalence of P. aeruginosa and A. fumigatus in CF. METHODS: The Embase, PubMed
      and Web of Science databases were systematically searched for studies reporting
      the co-colonization prevalence of P. aeruginosa and A. fumigatus in CF. The co
      colonization prevalence of two pathogenic microorganisms in the individual
      studies was assessed by calculating the proportion and 95% confidence interval
      (CI). The random effects model was used to calculate the pooled prevalence. The
      I2 test was used to assess statistical heterogeneity. The funnel plot and two
      statistical methods were used to assess publication bias. RESULTS: Twenty-three
      eligible studies were included in this analysis. The pooled co-colonization
      prevalence of P. aeruginosa and A. fumigatus in CF patients was 15.8% (95% CI:
      9.9-21.8). The co-colonization prevalence of P. aeruginosa and A. fumigatus
      chronic colonization was lower than that of intermittent colonization, higher in
      sputum cultures than in bronchoalveolar lavage (BAL) cultures, and lower in
      children than in adults. There was a statistically significant difference in co
      colonization prevalence among studies from different decades, but the prevalence
      was similar in different geographical regions and with different study types.
      CONCLUSIONS: The co-colonization prevalence of P. aeruginosa and A. fumigatus in
      the lower respiratory tract of CF patients was high. The anti-infective treatment
      in exacerbation of CF should be considered to cover the two pathogenic
      microorganisms simultaneously. Large-scale research is still needed to obtain
      more accurate co-colonization data.

PMID- 30217513
TI  - Combined Celiac Ganglia and Plexus Neurolysis Shortens Survival, Without Benefit,
      vs Plexus Neurolysis Alone.
AB  - BACKGROUND & AIMS: Pancreatic cancer produces debilitating pain that opioids
      often ineffectively manage. The suboptimal efficacy of celiac plexus neurolysis
      (CPN) might result from brief contact of the injectate with celiac ganglia. We
      compared the effects of endoscopic ultrasound-guided celiac ganglia neurolysis
      (CGN) vs the effects of CPN on pain, quality of life (QOL), and survival.
      METHODS: We performed a randomized, double-blind trial of patients with
      unresectable pancreatic ductal adenocarcinoma and abdominal pain; 60 patients
      (age 66.4+/-11.6 years; male 66%) received CPN and 50 patients (age 66.8+/-10.0
      years; male 56%) received CGN. Primary outcomes included pain control and QOL at
      week 12 and survival (overall median and 12 months). Secondary outcomes included
      morphine response, performance status, secondary neurolytic effects, and adverse
      events. RESULTS: Rates of pain response at 12 weeks were 46.2% for CGN and 40.4%
      for CPN (P=.84). There was no significant difference in improvement of QOL
      between the techniques. The median survival time was significantly shorter for
      patients receiving CGN (5.59 months) compared to (10.46 months) (hazard ratio for
      CGN, 1.49; 95% CI, 1.02-2.19; P=.042), particularly for patients with non
      metastatic disease (hazard ratio for CGN, 2.95; 95% CI, 1.61-5.45; P<.001). Rates
      of survival at 12 months were 42% for patients who underwent CPN vs 26% for
      patients who underwent CGN. The number of adverse events did not differ between
      techniques. CONCLUSION: In a prospective study of patients with unresectable
      pancreatic ductal adenocarcinoma and abdominal pain, we found CGN to reduce
      median survival time without improving pain, QOL, or adverse events, compared to
      CPN. The role of CGN must be therefore be reassessed. Clinicaltrials.gov no:
      NCT01615653.

PMID- 30217515
TI  - Palladium nanoparticles synthesis, characterization using glucosamine as the
      reductant and stabilizing agent to explore their antibacterial & catalytic
      applications.
AB  - Low cost and an easy technique for the synthesis of palladium nanoparticles
      (PdNPs) was developed. Glucosamine was used to stabilize palladium precursor
      (PdCl2) into palladium nanoparticles. Several analytical techniques were used for
      the determination of morphology, crystalline structure; size, capping, and
      composition of synthesize palladium nanoparticles. The UV-visible spectroscopy
      SPR peak (Surface Plasmon Resonance) at 284 nm revealed synthesis of PdNPs.
      Energy dispersive X-ray (EDX) and X-ray diffraction (XRD) studies proved the
      elemental composition and crystalline structure of the synthesized palladium
      nanoparticles respectively. The average particle sizes (5.5 nm) were obtained by
      using the 1 M glucosamine solution, with a fixed amount of PdCl2 (4 mM).
      Moreover, the as synthesized PdNPs was evaluated against Gram negative bacterial
      E. which shows tremendous antibacterial activity as compare to tobramycin
      standard antibiotics. It's mechanistically found that PdNPs damage cell membrane
      and caused imbalance of metabolism system of the cell as a result production of
      reactive oxygen species (ROS). Thus, these finding revealed that cells become
      leaky and all organelles come out from cells, finally caused death of the E.
      coli. Addition, the as prepared PdNPs also showed excellent catalytic activities
      toward reduction of methylene blue and 4-nitrophenol.Thus, glucosamine mediated
      PdNPs having dual functions biomedical as well as intoxicating catalyst for
      industries.

PMID- 30217516
TI  - Identification of novel immunoreactive proteins and delineation of a specific
      epitope of Anaplasma phagocytophilum.
AB  - Human granulocytic anaplasmosis (HGA), an increasingly recognized febrile tick
      borne illness, is caused by a gram-negative obligate intracellular bacterium
      Anaplasma phagocytophilum. Because of nonspecific clinical manifestations,
      diagnosis of HGA highly depends on laboratory tests. Identification of
      immunoreactive proteins is prerequisite for development of specific and sensitive
      immunoassays for HGA. In this study, we identified novel immunoreactive proteins
      of A. phagocytophilum. Previous studies indicated that secreted proteins of A.
      phagocytophilum and other bacteria can be immunoreactive antigens. Here we in
      silico screened A. phagocytophilum genome for encoding proteins which bear
      features of type IV secretion system substrates. Among seventy seven predicted
      proteins, fourteen proteins were determined for antigenicity and nine proteins
      were showed to be immunoreactive antigens. In addition, an APH1384 peptide
      harboring a B cell epitope predicted by bioinformatics was found specifically
      reacting with anti-A. phagocytophilum sera. Hereby, we identified novel
      immunoreactive proteins and delineated a specific epitope of A. phagocytophilum,
      which might be employed for HGA diagnosis.

PMID- 30217517
TI  - In silico identification of immunodominant B-cell and T-cell epitopes of non
      structural proteins of Usutu Virus.
AB  - Usutu Virus (USUV; flavivirus) is a re-emerging pathogen invading the territories
      of European countries, Asia, and Africa. It is a mosquito-borne zoonotic virus
      with a bi-directional transmission route from animal to human and vice versa, and
      causes neurological disorders such as meningoencephalitis in bats, Homo sapiens,
      birds and horses. Due to limited availability of information about USUV and its
      deleterious effects on neural cells causing neurologic impairments, it becomes
      imperative to study this virus in detail to equip ourselves with a solution
      beforehand. The current study aims to identify immunodominant peptides that could
      be exploited in future for designing global peptide vaccine for combating the
      infections caused by USUV. In this study, an immunoinformatics approach was
      applied to evaluate the immunogenicity of 7 non-structural proteins and
      determined 64 continuous B-cell epitopes, numerous probable discontinuous B-cell
      epitopes, 64 MHC Class-I binders, 126 MHC class-II binders and 52 promiscuous
      binders with a maximum population coverage of 98.55%(MHC Class-I binder
      ofYP_164815.1 NS4a) and 81.81% (MHC Class-II binders of YP_164812.1 NS2a,
      YP_164813.1 NS2b, YP_164814.1 NS3, YP_164817.1 NS4b, YP_164818.1 NS5). Further,
      studies involving experimental validation of these predicted epitopes is
      warranted to ensure the potential of B-cells and T-cells stimulation for their
      effective use as vaccine candidates, and as diagnostic agents against USUV.

PMID- 30217518
TI  - The effect of low- and high-penetration light on localized cancer therapy.
AB  - The design of a delivery system allowing targeted and controlled drug release has
      been considered one of the main strategies used to provide individualized cancer
      therapy, to improve survival statistics, and to enhance quality-of-life. External
      stimuli including low- and high-penetration light have been shown to have the
      ability to turn drug delivery on and off in a non-invasive remotely-controlled
      fashion. The success of this approach has been closely related to the development
      of a variety of drug delivery systems - from photosensitive liposomes to gold
      nanocages - and relies on multiple mechanisms of drug release activation. In this
      review, we make reference to the two extremes of the light spectrum and their
      potential as triggers for the delivery of antitumor drugs, along with the most
      recent achievements in preclinical trials and the challenges to an efficient
      translation of this technology to the clinical setting.

PMID- 30217519
TI  - Challenges and innovations of drug delivery in older age.
AB  - Both drug delivery performance and various age-related physical, mental and
      physiological changes can affect drug effectiveness and safety in elderly
      patients. The many drug delivery systems developed over the years include recent
      novel transdermal, nasal, pulmonary and orally disintegrating tablets that
      provide consistent, precise, timely and more targeted drug delivery. Certain drug
      delivery systems may be associated with suboptimal outcomes in the elderly
      because of the nature of drug present, a lack of appreciation of the impact of
      age-related changes in drug absorption, distribution and clearance, the limited
      availability of pharmacokinetic, safety and clinical data. Polypharmacy, patient
      morbidity and poor adherence can also contribute to sub-optimal drug delivery
      systems outcomes in the elderly. The development of drug delivery systems for the
      elderly is a poorly realised opportunity, with each system having specific
      advantages and limitations. A key challenge is to provide the innovation that
      best meets the specific physiological, psychological and multiple drug
      requirements of individual elderly patients.

PMID- 30217520
TI  - Association between itch and cancer in 16,925 pruritus patients: Experience at a
      tertiary care center.
AB  - BACKGROUND: Pruritus has been associated with cancer. However, limited data is
      available on the types of underlying malignancy associated with pruritus.
      OBJECTIVE: We sought to characterize the association between pruritus and
      different cancer types, as well as variations by racial group. METHODS: Cross
      sectional study of patients >= 18 years old seen at the Johns Hopkins Health
      System from 2013-2017. Patients with pruritus were compared to patients without
      pruritus. Analyses were stratified by race. RESULTS: Patients with pruritus are
      more likely to have concomitant malignancy than those without pruritus (OR 5.76;
      95% CI 5.53-6.00). Most strongly associated are cancers of the liver, gallbladder
      and biliary tract, hematopoietic system, and skin. Compared to whites, black
      patients more frequently have soft tissue, dermatological, and hematological
      malignancies, and less frequently have liver, respiratory, GI, and gynecological
      malignancies. LIMITATIONS: Cross-sectional design precludes analysis of the
      temporal association between pruritus and malignancy. The study is limited to a
      single tertiary care center. CONCLUSION: Pruritus is most strongly associated
      with cancers of the liver, skin, and hematopoietic system. Black patients with
      pruritus have a higher likelihood of skin, soft tissue, and hematological
      malignancies than whites, while whites have higher likelihood of liver,
      respiratory, GI, and gynecological malignancies.

PMID- 30217521
TI  - What is the functional relevance of reorganization in primary motor cortex after
      spinal cord injury?
AB  - Motor output maps within primary motor cortex are widely distributed and modified
      by motor skill learning and neurological injury. Functions that these maps
      represent after spinal cord injury remain debatable. Moreover, the pattern of
      reorganization and whether it supports recovery of compromised motor function is
      not well understood. A deeper understanding of the pathophysiological mechanisms
      of motor dysfunction after spinal cord injury is necessary to develop and
      optimize repair strategies. There are three purposes for this review. The first
      is to synthesize available research on spontaneous reorganization with primary
      motor cortex following spinal cord injury. The second is to draw on existing
      evidence from the motor skill learning and brain injury literature to interpret
      the form and purpose of motor maps. The third purpose is to account for the
      existing research on intervention-induced reorganization of primary motor cortex
      following spinal cord injury. We conclude with directions for future work,
      emphasizing the need for multi-modal investigations that construct maps with both
      neuroimaging and non-invasive stimulation methods to derive a cohesive
      understanding of the effects of spinal cord injury on reorganization within
      primary motor cortex.

PMID- 30217522
TI  - Examination of antigenic proteins of Trypanosoma cruzi to fabricate an epitope
      based subunit vaccine by exploiting epitope mapping mechanism.
AB  - Chagas disease is a protozoan parasitic disease caused by Trypanosoma cruzi. This
      injurious disease spread by the circulation of the blood sucking triatomine
      insects and transmitted to humans. Chagas disease is endemic in Latin America and
      also known as American trypanosomasis. Currently, 7 million people are infected
      by T. cruzi infection and about 22,000 death cases were reported per year
      throughout the Americas. Various immunization approaches against T. cruzi
      infection have been examined and some of the developed vaccine showed efficacy in
      animal models but there is no effective and safe vaccines for humans have been
      developed yet. Since, the drug resistance is increasing day by day because the
      developed drug (nifurtimox and benznidazole) to control T. cruzi infection,
      failed to activate a prodrug and still no drug and vaccine have been established.
      To control the infection of chagas disease, here in this study we use
      immunoinformatics method to design multi-epitope subunit vaccine against T. cruzi
      infection. Moreover, on the basis of immunogenicity B and T cell epitopes were
      evaluated. The allergenicity, antigenicity was predicted to ensure the safety of
      vaccine constructs whereas, the physiochemical property showing the stable nature
      of final vaccine model. Further, molecular docking was performed to optimize the
      interaction between TLR-2 and TLR-4 (receptor) and vaccine model (ligand)
      complex. Molecular dynamics simulation was performed to evaluate the energy
      minimization; RMSD and RMSF plot which confirm the stability of TLR-2 and TLR-4
      (receptor) present on immune cells and vaccine model (ligand) complex. This study
      needed the experimental validation for the safety and immunogenic behavior of
      designed vaccine protein and it may be helpful in future to control T. cruzi
      infection.

PMID- 30217523
TI  - Pneumococcal vaccination in adult solid organ transplant recipients: A review of
      current evidence.
AB  - This narrative review summarizes the current literature relating to pneumococcal
      vaccination in adult solid organ transplant (SOT) recipients, who are at risk of
      invasive pneumococcal disease (IPD) with its attendant high morbidity and
      mortality. The effect of the pneumococcal polysaccharide vaccine has been
      examined in several small cohort studies in SOT recipients, most of which were
      kidney transplant recipients. The outcomes for these studies have been laboratory
      seroresponses or functional antibody titers. Overall, in most of these studies
      the transplant recipients were capable of generating measurable serological
      responses to pneumococcal vaccination but these responses were less than those of
      healthy controls. A mathematical model estimated the effectiveness of
      polysaccharide vaccination in SOT recipients to be one third less than those of
      patients with HIV. The evidence for the efficacy of the pneumococcal conjugate
      vaccine in SOT is based on a small number of randomized controlled trials in
      liver and kidney transplant recipients. These trials demonstrated that SOT
      recipients mounted a serological response following vaccination however there was
      no benefit to the use of prime boosting (conjugate vaccine followed by
      polysaccharide vaccine). Currently there are no randomized studies investigating
      the clinical protection rate against IPD after pneumococcal vaccination by either
      vaccine type or linked to vaccine titers or other responses against pneumococcus.
      Concerns that vaccination may increase the risk of adverse alloresponses such as
      rejection and generation of donor specific antibodies are not supported by
      studies examining this aspect of vaccine safety. Pneumococcal vaccination is a
      potentially important strategy to reduce IPD in SOT recipients and is associated
      with excellent safety. Current international recommendations are based on expert
      opinion from conflicting data, hence there is a clear need for further high
      quality studies in this high-risk population examining optimal vaccination
      regimens. Such studies should focus on strategies to optimize functional immune
      responses.

PMID- 30217525
TI  - Gender difference in Brugada syndrome: Mirror images of long QT syndrome?

PMID- 30217524
TI  - Intranasal immunization with immunodominant epitope peptides derived from HpaA
      conjugated with CpG adjuvant protected mice against Helicobacter pylori
      infection.
AB  - HpaA is considered to be an effective protective antigen for vaccination against
      Helicobacter pylori (H. pylori) infection. Oral immunization with HpaA
      significantly decreases bacterial colonization in H. pylori infected mice. In
      this study, we investigated whether subcutaneous or intranasal immunization with
      HpaA could protect against H. pylori infection. Mice immunized subcutaneously
      with HpaA in Complete Freund's adjuvant, but not mice intranasally immunized with
      HpaA in CpG adjuvant acquired protection against H. pylori infection. However,
      intranasal immunization with immunodominant epitope peptides in CpG adjuvant
      protected mice against H. pylori infection, and immunodominant epitope peptides
      stimulated stronger Th1 responses and mediated more robust protection against H.
      pylori infection than subdominant ones. Our results suggest that the length of a
      candidate antigen is critical for particular vaccination routes, and that
      immunodominant epitope peptides are promising candidates for protection against
      H. pylori infection through nasal vaccination.

PMID- 30217526
TI  - To the Editor- The anatomy of para-Hisian arrhythmias.

PMID- 30217527
TI  - Beyond the exercise stress test: Does the cardiac ryanodine receptor affect
      intellectual function?

PMID- 30217528
TI  - Seminars in Thoracic and Cardiovascular Surgery - Current Readings: Adult
      Congenital Heart Surgery.
AB  - While the incidence of congenital heart disease has remained relatively stable,
      survival has increased dramatically. Many of these patients require lifelong
      specialized cardiac care to address sequelae and residual disease. In order to
      best meet the increasing demands and needs of this heterogeneous group of
      survivors, multidisciplinary specialty training, lesion specific outcomes
      research and both personnel and financial resources must be dedicated to their
      care.

PMID- 30217529
TI  - Reslizumab Compared with Benralizumab in Patients with Eosinophilic Asthma: A
      Systematic Literature Review and Network Meta-Analysis.
AB  - BACKGROUND: The interaction of IL-5 with its receptor on eosinophils increases
      the activation and maintenance of eosinophils; blocking this interaction reduces
      asthma symptoms in patients with the eosinophilic phenotype. Reslizumab, which
      binds to IL-5, and benralizumab, which targets the IL-5 receptor alpha subunit,
      have not been compared in head-to-head trials. OBJECTIVE: To indirectly compare
      reslizumab with benralizumab in similar patient populations using a network meta
      analysis. METHODS: A systematic literature review was conducted and a network
      meta-analysis was performed on eligible studies using the Markov Chain Monte
      Carlo simulation method and a Bayesian statistical framework. RESULTS: Eleven
      studies were identified, 4 of which evaluated clinically relevant doses and had
      outcomes at similar time points. To control for population differences, subgroups
      were selected for the base-case efficacy analysis: a benralizumab subgroup with
      blood eosinophil levels of greater than or equal to 300 cells/MUL (n = 1537) and
      a reslizumab subgroup in Global Initiative for Asthma step 4/5 with 2 or more
      previous exacerbations and greater than or equal to 400 eosinophils/MUL (n =
      318). Safety was analyzed in the full population (N = 3462). Reslizumab
      significantly improved Asthma Control Questionnaire (ACQ) and Asthma Quality of
      Life Questionnaire (AQLQ) scores compared with benralizumab once every 4 weeks
      and there were reasonably high posterior probabilities that reslizumab is
      superior to benralizumab once every 4 weeks and once every 8 weeks for ACQ score,
      AQLQ score, FEV1, and clinical asthma exacerbations. CONCLUSIONS: This indirect
      comparison suggests that reslizumab may be more efficacious than benralizumab in
      patients with eosinophilic asthma in Global Initiative for Asthma step 4/5 with
      elevated blood eosinophil levels (benralizumab, >=300/MUL; reslizumab, >=400/MUL)
      and 2 or more exacerbations in the previous year.

PMID- 30217530
TI  - Anaphylaxis to trometamol excipient in gadolinium-based contrast agents for
      clinical imaging.

PMID- 30217531
TI  - A CRISPR/Cas9 platform for MS2-labelling of single mRNA in live stem cells.
AB  - The MS2 system is a powerful tool for investigating transcription dynamics at the
      single molecule directly in live cells. In the past, insertion of the RNA
      labelling cassette at specific gene loci has been a major hurdle. Here, we
      present a CRISPR/Cas9-based approach to insert an MS2 cassette with selectable
      marker at the start of the 3' untranslated region of any coding gene. We
      demonstrate applicability of our approach by tagging RNA of the stem cell
      transcription factor Esrrb in mouse embryonic stem cells. Using quantitative
      fluorescence microscopy we determine the number of nascent transcripts at the
      Esrrb locus and the fraction of cells expressing the gene. We find that upon
      differentiation towards epiblast-like cells, expression of Esrrb is down
      regulated in an increasing fraction of cells in a binary manner.

PMID- 30217532
TI  - Pathways linking childhood abuse history and current socioeconomic status to
      inflammation during pregnancy.
AB  - Women who have experienced significant adversities during childhood and adulthood
      are at risk for excessive inflammation during pregnancy, but the mechanisms are
      unclear. Using structural equation modeling, we examined pathways from childhood
      abuse history and current socioeconomic status (SES) to inflammatory markers
      through indicators of health risk, recent stressors, and psychological distress
      in 214 women assessed at mid-pregnancy (5-31 weeks gestation). Self-reported data
      on socioeconomic indicators, childhood trauma history, pre-pregnancy body mass
      index (BMI), smoking, sleep quality, interpersonal conflict, recent life events,
      perceived stress, and depressive symptoms were collected, and serum levels of C
      reactive protein (CRP) and interleukin (IL)-6 were determined. In separate
      models, pre-pregnancy BMI, sleep quality, and interpersonal conflict
      statistically explained the relationship between adversity and inflammation.
      These three intermediate variables were then entered into a multiple mediation
      analysis to examine unique effects. Childhood abuse history and current SES both
      demonstrated significant indirect effects on CRP through pre-pregnancy BMI, and
      current SES showed a significant indirect effect on IL-6 through all intermediate
      variables. When examining each indirect pathway individually, pre-pregnancy BMI
      and interpersonal conflict emerged as parallel pathways by which low current SES
      leads to elevated IL-6; the indirect pathway through sleep quality was no longer
      significant. Pre-pregnancy BMI and interpersonal conflict are two independent
      mechanisms by which adversity is associated with increased inflammation during
      pregnancy. Women who have been exposed to significant adversity may be at
      particular risk for obesity, sleep disruption, and interpersonal conflict, with
      implications for immune dysregulation during pregnancy.

PMID- 30217533
TI  - Platelets mediate protective neuroinflammation and promote neuronal plasticity at
      the site of neuronal injury.
AB  - It is generally accepted that inflammation within the CNS contributes to
      neurodegeneration after traumatic brain injury (TBI), but it is not clear how
      inflammation is initiated in the absence of infection and whether this
      neuroinflammation is predominantly beneficial or detrimental. We have previously
      found that brain-enriched glycosphingolipids within neuronal lipid rafts (NLR)
      induced platelet degranulation and secretion of neurotransmitters and pro
      inflammatory factors. In the present study, we compared TBI-induced inflammation
      and neurodegeneration in wild-type vs. St3gal5 deficient (ST3-/-) mice that lack
      major CNS-specific glycosphingolipids. After TBI, microglial activation and CNS
      macrophage infiltration were substantially reduced in ST3-/- animals. However,
      ST3-/- mice had a larger area of CNS damage with marked neuronal/axonal loss. The
      interaction of platelets with NLR stimulated neurite growth, increased the number
      of PSD95-positive dendritic spines, and intensified neuronal activity. Adoptive
      transfer and blocking experiments provide further that platelet-derived serotonin
      and platelet activating factor plays a key role in the regulation of sterile
      neuroinflammation, hemorrhage and neuronal plasticity after TBI.

PMID- 30217534
TI  - Chronic interleukin-1beta in the dorsal hippocampus impairs behavioural pattern
      separation.
AB  - Understanding the long-term consequences of chronic inflammation in the
      hippocampus may help to develop therapeutic targets for the treatment of
      cognitive disorders related to stress, ageing and neurodegeneration. The
      hippocampus is particularly vulnerable to increases in the pro-inflammatory
      cytokine interleukin-1beta (IL-1beta), a mediator of neuroinflammation, with
      elevated levels implicated in the aetiology of neurodegenerative diseases such as
      Alzheimer's and Parkinson's, and in stress-related disorders such as depression.
      Acute increases in hippocampal IL-1beta have been shown to impair cognition and
      reduce adult hippocampal neurogenesis, the birth of new neurons. However, the
      impact of prolonged increases in IL-1beta, as evident in clinical conditions, on
      cognition has not been fully explored. Therefore, the present study utilized a
      lentiviral approach to induce long-term overexpression of IL-1beta in the dorsal
      hippocampus of adult male Sprague Dawley rats and examine its impact on
      cognition. Following three weeks of viral integration, pattern separation, a
      process involving hippocampal neurogenesis, was impaired in IL-1beta-treated rats
      in both object-location and touchscreen operant paradigms. This was coupled with
      a decrease in the number and neurite complexity of immature neurons in the
      hippocampus. Conversely, tasks involving the hippocampus, but not sensitive to
      disruption of hippocampal neurogenesis, including spontaneous alternation, novel
      object and location recognition were unaffected. Touchscreen operant visual
      discrimination, a cognitive task involving the prefrontal cortex, was largely
      unaffected by IL-1beta overexpression. In conclusion, these findings suggest that
      chronically elevated IL-1beta in the hippocampus selectively impairs pattern
      separation. Inflammatory-mediated disruption of adult hippocampal neurogenesis
      may contribute to the cognitive decline associated with neurodegenerative and
      stress-related disorders.

PMID- 30217535
TI  - Microglia have a protective role in viral encephalitis-induced seizure
      development and hippocampal damage.
AB  - In the central nervous system (CNS), innate immune surveillance is mainly
      coordinated by microglia. These CNS resident myeloid cells are assumed to help
      orchestrate the immune response against infections of the brain. However, their
      specific role in this process and their interactions with CNS infiltrating immune
      cells, such as blood-borne monocytes and T cells are only incompletely
      understood. The recent development of PLX5622, a specific inhibitor of colony
      stimulating factor 1 receptor that depletes microglia, allows studying the role
      of microglia in conditions of brain injury such as viral encephalitis, the most
      common form of brain infection. Here we used this inhibitor in a model of viral
      infection-induced epilepsy, in which C57BL/6 mice are infected by a picornavirus
      (Theiler's murine encephalomyelitis virus) and display seizures and hippocampal
      damage. Our results show that microglia are required early after infection to
      limit virus distribution and persistence, most likely by modulating T cell
      activation. Microglia depletion accelerated the occurrence of seizures,
      exacerbated hippocampal damage, and led to neurodegeneration in the spinal cord,
      which is normally not observed in this mouse strain. This study enhances our
      understanding of the role of microglia in viral encephalitis and adds to the
      concept of microglia-T cell crosstalk.

PMID- 30217536
TI  - Sickness behavior is not all about the immune response: Possible roles of
      expectations and prediction errors in the worry of being sick.
AB  - BACKGROUND: People react very differently when sick, and there are only poor
      correlations between the intensity of the immune response and sickness behavior.
      Yet, alternative predictors of the individual differences in sickness are under
      investigated. Based on the predictive coding model of placebo responses, where
      health outcomes are function of bottom-up sensory information and top-down
      expectancies, we hypothesized that individual differences in behavioral changes
      during sickness could be explained by individual top-down expectancies and
      prediction errors. METHODS: Twenty-two healthy participants were made sick by
      intravenously administering lipopolysaccharide (2 ng/kg body weight). Their
      expectations of becoming sick were assessed before the injection. RESULTS:
      Participants having lower expectations of becoming sick before the injection
      reacted with more emotional distress (i.e., more negative affect and lower
      emotional arousal) than those with high expectations of becoming sick, despite
      having similar overall sickness behavior (i.e., a combined factor including
      fatigue, pain, nausea and social withdrawal). In keeping with a predictive coding
      model, the "prediction error signal", i.e., the discrepancy between the immune
      signal and sickness expectancy, predicted emotional distress (reduction in
      emotional arousal in particular). CONCLUSION: The current findings suggest that
      the emotional component of sickness behavior is, at least partly, shaped by top
      down expectations. Helping patients having a realistic expectation of symptoms
      during treatment of an illness may thus reduce aggravated emotional responses,
      and ultimately improve patients' quality of life and treatment compliance.
      REGISTRATION: "Endotoxin-induced Inflammatory and Behavioral Responses and
      Predictors of Individual Differences",
      https://clinicaltrials.gov/ct2/show/NCT02529592, registration number:
      NCT02529592.

PMID- 30217537
TI  - Differential regulation of NF-kB and IRF target genes as they relate to fatigue
      in patients with head and neck cancer.
AB  - Previous studies have linked plasma inflammatory markers to elevated fatigue in
      patients with head and neck cancer (HNC). To identify the molecular mechanisms
      underlying this association, we conducted promoter-based bioinformatics analyses
      to determine the relationship between fatigue and specific gene expression
      profiles associated with inflammation in human papillomavirus (HPV)-related and 
      unrelated HNC patients undergoing treatment. Patients with newly diagnosed HNC
      without distant metastasis were assessed at baseline (pre-radiotherapy) and one
      month post-radiotherapy. Fatigue was measured by the Multidimensional Fatigue
      Inventory. Genome-wide gene expression profiles were collected from peripheral
      blood mononuclear cells (PBMC). Promoter-based bioinformatics analyses were
      employed to identify transcription control pathways underlying transcriptomic
      correlates of fatigue in the sample as a whole and in HPV-related and HPV
      unrelated HNC patients separately. In transcriptome profiling analyses of PBMC
      from 44 patients, TELiS bioinformatics analyses linked fatigue to increased
      nuclear factor-kappa B (NF-kB) transcriptional activity and decreased interferon
      regulatory factor family (IRF) transcription factor activity. Patients with HPV
      related HNC showed lower levels of fatigue-related gene expression profile
      compared to HPV-unrelated HNC. Fatigue in HNC patients undergoing treatment is
      associated with gene expression profiles consistent with the conserved
      transcriptional response to adversity (CTRA) characterized by increased
      proinflammatory and decreased anti-antiviral transcriptional activity.
      Interestingly, this CTRA response was mitigated in patients with HPV-related HNC
      and may explain the lower level of fatigue they experience relative to HPV
      unrelated HNC.

PMID- 30217538
TI  - Negative and positive affect as predictors of inflammation: Timing matters.
AB  - Very little research has assessed how measures of negative and positive affect
      (NA and PA) derived from assessments at multiple time points per day (e.g., via
      ecological momentary assessment [EMA]), as opposed to questionnaires that rely on
      recall over a longer period, are related to levels of peripheral inflammation. We
      examined how different indicators of NA and PA predicted concentrations of C
      reactive protein (CRP) and seven peripheral inflammatory cytokines (IL-1beta, IL
      6, TNF-alpha, IL-8, IL-4, IL-10, and IFN-gamma) that were examined in the form of
      an inflammatory composite. A community-based sample of 220 adults (62%
      Black/African-American and 25% Hispanic/Latino; aged 25-65; 65% female) completed
      questionnaires at baseline (including recalled affect "over the past month") and
      then provided EMA reports 5x/day for 14 days. Blood was drawn from each
      participant after completion of EMA and used to determine plasma levels of CRP
      and cytokines. Analyses examined if indicators of affect predicted inflammation,
      controlling for age, gender, body mass index, education, health conditions, and
      statin use. Neither recalled NA or PA nor momentary NA or PA (aggregated across
      the 14 days of EMA) were significantly associated with the cytokine composite or
      CRP. Negative mood more proximal to the blood draw (i.e., aggregated momentary NA
      in week 2 of EMA) was associated with the cytokine composite but not CRP.
      Exploratory moderation analyses revealed that the cytokine composite was also
      associated with PA in week 2 for men only, and with recalled NA for those with
      lower education. Exploratory analyses around temporal dynamics suggested that the
      timing of NA measurement relative to the blood draw mattered: Specifically, there
      were stronger trends of association between momentary NA and inflammatory
      cytokines when NA was assessed closer in time to blood collection. Future
      investigation of the relevance of temporal proximity and other measurement
      details may improve understanding of how affect relates to inflammation.

PMID- 30217539
TI  - Cannabidiol prevents haloperidol-induced vacuos chewing movements and
      inflammatory changes in mice via PPARgamma receptors.
AB  - The chronic use of drugs that reduce the dopaminergic neurotransmission can cause
      a hyperkinetic movement disorder called tardive dyskinesia (TD). The
      pathophysiology of this disorder is not entirely understood but could involve
      oxidative and neuroinflammatory mechanisms. Cannabidiol (CBD), the major non
      psychotomimetic compound present in Cannabis sativa plant, could be a possible
      therapeutic alternative for TD. This phytocannabinoid shows antioxidant, anti
      inflammatory and antipsychotic properties and decreases the acute motor effects
      of classical antipsychotics. The present study investigated if CBD would
      attenuate orofacial dyskinesia, oxidative stress and inflammatory changes induced
      by chronic administration of haloperidol in mice. Furthermore, we verified in
      vivo and in vitro (in primary microglial culture) whether these effects would be
      mediated by PPARgamma receptors. The results showed that the male Swiss mice
      treated daily for 21 days with haloperidol develop orofacial dyskinesia. Daily
      CBD administration before each haloperidol injection prevented this effect. Mice
      treated with haloperidol showed an increase in microglial activation and
      inflammatory mediators in the striatum. These changes were also reduced by CBD.
      On the other hand, the levels of the anti-inflammatory cytokine IL-10 increased
      in the striatum of animals that received CBD and haloperidol. Regarding oxidative
      stress, haloperidol induced lipid peroxidation and reduced catalase activity.
      This latter effect was attenuated by CBD. The combination of CBD and haloperidol
      also increased PGC-1alpha mRNA expression, a co-activator of PPARgamma receptors.
      Pretreatment with the PPARgamma antagonist, GW9662, blocked the behavioural
      effect of CBD in our TD model. CBD also prevented LPS-stimulated microglial
      activation, an effect that was also antagonized by GW9662. In conclusion, our
      results suggest that CBD could prevent haloperidol-induced orofacial dyskinesia
      by activating PPARgamma receptors and attenuating neuroinflammatory changes in
      the striatum.

PMID- 30217540
TI  - Post-operative electrode location and clinical efficacy of subthalamic nucleus
      deep brain stimulation in Meige syndrome.
AB  - BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) has recently
      been shown to be an effective treatment for Meige syndrome but efficacy of
      symptomatic improvement and its relationship to factors in DBS remains to be
      explored. OBJECTIVES: This study explored the relationship of electrode contact
      location in bilateral STN-DBS with clinical efficacy in Meige syndrome patients
      through retrospective analysis. METHODS: Pre- and post-operative magnetic
      resonance (MR) images of Meige syndrome patients (n = 15) were analysed. Clinical
      outcomes were evaluated with the Burke-Fahn-Marsden Dystonia Scale (BFMDRS). The
      location of active contacts in Montreal Neurological Institute (MNI) standard
      space and volume of activated STN tissue were determined and related to clinical
      outcomes. RESULTS: At the last follow up (mean = 14.8 +/- 4.0 months; range = 11
      24 months), Meige syndrome patients (n = 14) showed improved BFMDRS scores (mean
      improvement = 70.9%, p = 0.001) compared to pre-operative assessment. Active
      contacts of stimulation given from coordinates in the MNI space (mean left side:
      x = -12.5 +/- 1.2 mm, y = -13.3 +/- 1.7 mm, z = -5.5 +/- 2.5 mm; mean right side:
      x = 12.7 +/- 1.4 mm, y = -12.7 +/- 1.7 mm, z = -6.4 +/- 2.4 mm) were found mainly
      clustered in the dorsolateral STN. While there were no significant differences in
      patients grouped by their degree of symptomatic improvement (<30%, 30-70% and
      >70%) with their respective coordinates, the volume of activated tissue within
      the STN of patients was significantly correlated to the BFMDRS improvement (R =
      0.6, p = 0.02). CONCLUSIONS: These findings further support the stimulation of
      the dorsolateral STN for effective alleviation of symptoms in Meige syndrome
      patients and indicate that specific factors of DBS can be considered to predict
      clinical efficacy.

PMID- 30217541
TI  - Inferring the long duration response to levodopa in Parkinson's disease.
AB  - INTRODUCTION: The long duration response to levodopa in Parkinson's disease
      outlasts drug elimination by days to weeks. Though a substantive part of anti
      parkinsonian motor benefit, it cannot easily be observed. OBJECTIVES: To infer
      the magnitude of the long duration response during the first decade of
      Parkinson's disease and identify factors that influence it. METHODS: Serial
      practically defined off scores of 24 patients from a longitudinal study of
      levodopa short duration response were used to establish their rate of motor
      progression. A line of notional untreated disability (as if drug treatment had
      never been given) with the same progression gradient was the basis for
      calculation of the long duration response. Predictors of mean long duration
      response amplitude were identified using a multiple linear regression model.
      RESULTS: Over a mean treatment period of 16.6 +/- 4.4 years, annual increase in
      motor disability was 2.3% of the maximum score. The long duration response
      composed 49% of total levodopa response during the first decade of treatment, and
      this proportion was significantly higher soon after commencing levodopa (p =
      0.001). Higher pre-treatment motor score (r = 0.60) and lower MMSE (r = 0.60)
      were the main predictors of a larger long duration response. There was little
      correlation between long and short duration responses. CONCLUSIONS: Long duration
      responses contribute almost half of the total levodopa benefit during the first
      decade of treatment. An appreciation of both long and short duration components
      of drug symptomatic effects is important in clinical trial design to investigate
      possible neuroprotective treatments.

PMID- 30217543
TI  - Shared understanding of narratives is correlated with shared neural responses.
AB  - Humans have a striking ability to infer meaning from even the sparsest and most
      abstract forms of narratives. At the same time, flexibility in the form of a
      narrative is matched by inherent ambiguity in its interpretation. How does the
      brain represent subtle, idiosyncratic differences in the interpretation of
      abstract and ambiguous narratives? In this fMRI study, subjects were scanned
      either watching a novel 7-min animation depicting a complex narrative through the
      movement of geometric shapes, or listening to a narration of the animation's
      social story. Using an intersubject representational similarity analysis that
      compared interpretation similarity and neural similarity across subjects, we
      found that the more similar two people's interpretations of the abstract shapes
      animation were, the more similar were their neural responses in regions of the
      default mode network (DMN) and fronto-parietal network. Moreover, these shared
      responses were modality invariant: the shapes movie and the verbal interpretation
      of the movie elicited shared responses in linguistic areas and a subset of the
      DMN when subjects shared interpretations. Together, these results suggest a
      network of high-level regions that are not only sensitive to subtle individual
      differences in narrative interpretation during naturalistic conditions, but also
      resilient to large differences in the modality of the narrative.

PMID- 30217542
TI  - A face is more than just the eyes, nose, and mouth: fMRI evidence that face
      selective cortex represents external features.
AB  - What is a face? Intuition, along with abundant behavioral and neural evidence,
      indicates that internal features (e.g., eyes, nose, mouth) are critical for face
      recognition, yet some behavioral and neural findings suggest that external
      features (e.g., hair, head outline, neck and shoulders) may likewise be processed
      as a face. Here we directly test this hypothesis by investigating how external
      (and internal) features are represented in the brain. Using fMRI, we found highly
      selective responses to external features (relative to objects and scenes) within
      the face processing system in particular, rivaling that observed for internal
      features. We then further asked how external and internal features are
      represented in regions of the cortical face processing system, and found a
      similar division of labor for both kinds of features, with the occipital face
      area and posterior superior temporal sulcus representing the parts of both
      internal and external features, and the fusiform face area representing the
      coherent arrangement of both internal and external features. Taken together,
      these results provide strong neural evidence that a "face" is composed of both
      internal and external features.

PMID- 30217544
TI  - Temporal Derivative Distribution Repair (TDDR): A motion correction method for
      fNIRS.
AB  - Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging
      technique of growing interest as a tool for investigation of cortical activity.
      Due to the on-head placement of optodes, artifacts arising from head motion are
      relatively less severe than for functional magnetic resonance imaging (fMRI).
      However, it is still necessary to remove motion artifacts. We present a novel
      motion correction procedure based on robust regression, which effectively removes
      baseline shift and spike artifacts without the need for any user-supplied
      parameters. Our simulations show that this method yields better activation
      detection performance than 5 other current motion correction methods. In our
      empirical validation on a working memory task in a sample of children 7-15 years,
      our method produced stronger and more extensive activation than any of the other
      methods tested. The new motion correction method enhances the viability of fNIRS
      as a functional neuroimaging modality for use in populations not amenable to
      fMRI.

PMID- 30217545
TI  - The developmental trajectory of sensorimotor cortical oscillations.
AB  - Numerous studies of motor control have confirmed beta and gamma oscillations in
      the primary motor cortices during basic movements. These responses include a
      robust beta decrease that precedes and extends through movement onset, a
      transient gamma response that coincides with the movement, and a post-movement
      beta rebound (PMBR) response that occurs after movement offset. While the
      existence of these responses has been confirmed by many studies, very few studies
      have examined their developmental trajectory. In the current study, we utilized
      magnetoencephalography (MEG) to investigate age-related changes in sensorimotor
      cortical oscillations in a large cross-section of children and adolescents (n =
      94; age range = 9 -15 years-old). All participants performed a stimulus detection
      task with their right finger and the resulting MEG data were examined using
      oscillatory analysis methods and imaged using a beamformer. Consistent with adult
      studies, these youth participants exhibited characteristic beta (16-24 Hz)
      decreases prior to and during movement, as well as PMBR responses following
      movement offset, and a transient gamma (74-84 Hz) response during movement
      execution. Our primary findings were that the strength of the PMBR increased with
      age, while the strength of the gamma synchronization decreased with chronological
      age. In addition, the strength of each motor-related oscillatory response was
      significantly correlated with the power of spontaneous activity in the same
      frequency range and same voxel. This was the case for all three oscillatory
      responses. In conclusion, we investigated motor-related oscillatory activity in
      the largest cohort of children and adolescents reported to date, and our results
      indicated that beta and gamma cortical oscillations continue to develop as
      children transition into adolescents, and that these responses may not be fully
      matured until young to middle adulthood.

PMID- 30217546
TI  - False-positive cannabinoid screens in adult cystic fibrosis patients treated with
      lumacaftor/ivacaftor.

PMID- 30217547
TI  - A strategy for the discovery and validation of toxicity quality marker of Chinese
      medicine based on network toxicology.
AB  - BACKGROUND: Considering that the quality control indicators in Chinese medicine
      (CM) are disconnected from safety and effectiveness, Prof. Chang-xiao Liu et al.
      has proposed a concept regarding the quality marker (Q-marker) of CM to promote
      the healthy development of the CM industry and improve the CM quality control
      method. PURPOSE: In this study, we proposed a strategy to discover and verify the
      toxicity Q-marker of CM based on network toxicology. METHODS: First, traditional
      biochemical pathology indicators and sensitive biomarkers were used to predict
      the toxicity of CM. Next, the chemical composition of toxic CMs and their
      metabolites were rapidly identified by multidimensional detection techniques.
      Subsequently, the interaction network between "toxicity - toxic chemical
      composition - toxic target - effect pathway" was built through network
      toxicology, and the potential toxicity Q-marker of CM was initially screened.
      Finally, the chemical properties of toxicity Q-markers were verified by
      traceability and testability. RESULTS: Based on the predicted results of network
      toxicology, the toxic compounds of CM were preliminarily identified, and the
      toxic mechanism was comprehensively interpreted. In the context of definite
      biological properties and chemical properties, the toxicity Q-marker was finally
      confirmed. CONCLUSION: This extensive review provides a study method for the
      toxicity Q-marker of CM, which helps to systemically and thoroughly reveal the
      internal toxicity mechanism of CM. The in-depth study of the toxicity Q-marker
      provides the material basis and technical support for the safety evaluation of
      CM.

PMID- 30217548
TI  - First report of blaOXA-24 carbapenemase-encoding gene, armA Methyltransferase and
      aac(6)-Ib-cr producing multidrug-resistant clinical isolates of Proteus mirabilis
      in Algeria.
AB  - BACKGROUND: Carbapenemase-producing, or carbapenem-resistant Enterobacteriaceae,
      are an emerging threat to human and animal health because they are resistant to
      many of the last-line antimicrobials available for disease treatment. The aim of
      this study was to analyze antimicrobial resistance patterns and their encoding
      genes of P. mirabilis isolated in Constantine, Algeria. METHODS: A total of 106
      PMP (Proteus- Morganella- Providencia) strains were isolated from a large variety
      of clinical specimens, at University Hospital of Constantine in Algeria, and
      identified by the API 20E system and Bruker MALDI Biotyper 2.0 (MALDI-TOF/MS)
      platforms for microbial identification. Diagnostic accuracy was determined by
      independent comparison of each method to phylogenetic analysis based on the 16S
      rRNA gene sequencing. Antimicrobial susceptibility was determined using disc
      diffusion and E-test methods The presence of antibiotic resistance genes was
      screened for by PCR amplification and sequencing. RESULTS: a total of 72 PMP
      strains were multidrug- resistant. Among them, one isolate was resistant to
      imipenem with minimum inhibitory concentration>=12MUg/ml. PCR and sequencing
      showed the presence of different antibiotic resistance encoding genes: blaCTX-M
      15, blaTEM-1, blaTEM-2,blaPER-1, blaSHV-11, aadA1, aadA2, armA, aac(6')-Ib,
      aac(6')-Ib-cr, aac(3)-Ia, ant(2")-I, and forming different profiles. Moreover,
      the blaOXA-24 gene was detected in the imipenem-resistant strain. CONCLUSION: in
      this study, we found for the first time in Algeria a multidrug resistant P.
      mirabilis isolates harboring blaOXA-24, armA 16S rRNA methylase and aac(6)-Ib-cr
      gene.

PMID- 30217549
TI  - Giant cell arteritis and inflammatory bowel disease - Is there a connection?
      Results from a population-based study.
AB  - BACKGROUND: Giant cell arteritis (GCA) is an autoimmune disorder which primarily
      affects large vessels, whilst inflammatory bowel diseases (IBD) mainly target the
      gut. Co-existence of the two maladies has been reported sporadically in the
      literature; therefore the purpose of this study was to assess the authenticity of
      such an association in a large, cross-sectional study. METHODS: Utilizing data
      derived from the Clalit Health Services' registry, the largest health maintenance
      organization in Israel, we compared the proportion of CD and UC in GCA patients
      with age- and gender-matched controls. Univariate analysis was performed using
      Chi-square and student t-test and a multivariate analysis was performed using a
      logistic regression model. RESULTS: The study included 3938 GCA patients and
      21,623 age- and gender-matched controls. GCA patients had a significantly
      increased proportion of both CD and UC in comparison with controls (0.79% vs.
      0.12% and 0.84% vs. 0.21%, P-value < .001, respectively). The strength of the
      association between GCA and IBD was negatively correlated with the patients' age;
      thus the association was more robust amongst middle-aged patients (ages 50-69, OR
      = 8.13) than in elderly patients (ages 70-85, OR = 3.81). The association between
      GCA and IBD remained significant when evaluated independently of confounding
      factors (OR = 2.63, P-value < .001). CONCLUSIONS: The probability that GCA
      patients also suffer from IBD is increased in comparison with age- and gender
      matched controls. Our findings indicate that this association is more prominent
      in middle-aged patients (50-69 years of age). Screening for IBD amongst GCA
      patients in this age group may be warranted.

PMID- 30217550
TI  - Neutrophils: Novel key players in Rheumatoid Arthritis. Current and future
      therapeutic targets.
AB  - Rheumatoid Arthritis (RA) is a complex systemic autoimmune disease in which
      various cell types are involved. Among them, neutrophils have been recognized as
      important players in the onset and the progression of RA. The pathogenic role of
      neutrophils in RA lies in the alteration of several processes, including
      increased cell survival and migratory capacity, abnormal inflammatory activity,
      elevated oxidative stress and an exacerbated release of neutrophil extracellular
      traps. Through these mechanisms, neutrophils can activate other immune cells,
      thus perpetuating inflammation and leading to the destruction of the cartilage
      and bone of the affected joint. Given the considerable contribution of
      neutrophils to the pathophysiology of RA, several studies have attempted to
      clarify the effects of various therapeutic agents on this subtype of leukocyte.
      To date, recent studies have envisaged the role of new molecules on the
      pathogenic profile of neutrophils in RA, which could represent novel targets in
      future therapies. In this review, we aim to review the pathogenic role of
      neutrophils in RA, the effect of conventional treatments and biologic therapies,
      and the new, potential targets of neutrophil-derived molecules for the treatment
      of RA.

PMID- 30217551
TI  - Rapid acquisition of dynamic control over DLPFC using real-time fMRI feedback.
AB  - It has been postulated that gaining control over activity in the dorsolateral
      prefrontal cortex (DLPFC), a key region of the working memory brain network, may
      be beneficial for cognitive performance and treatment of certain psychiatric
      disorders. Several studies have reported that, with neurofeedback training,
      subjects can learn to increase DLPFC activity. However, improvement of dynamic
      control in terms of switching between low and high activity in DLPFC brain states
      may potentially constitute more effective self-regulation. Here, we report on
      feasibility of obtaining dynamic control over DLPFC, meaning the ability to both
      in- and decrease activity at will, within a single functional MRI scan session.
      Two groups of healthy volunteers (N = 24) were asked to increase and decrease
      activity in the left DLPFC as often as possible during fMRI scans (at 7 Tesla),
      while receiving real-time visual feedback. The experimental group practiced with
      real-time feedback, whereas the control group received sham feedback. The
      experimental group significantly increased the speed of intentionally alternating
      DLPFC activity, while performance of the control group did not change. Analysis
      of the characteristics of the BOLD signal during successful trials revealed that
      training with neurofeedback predominantly reduced the time for the DLPFC to
      return to baseline after activation. These results provide a preliminary
      indication that people may be able to learn to dynamically down-regulate the
      level of physiological activity in the DLPFC, and may have implications for
      psychiatric disorders where DLPFC plays a role.

PMID- 30217552
TI  - Effects of high-dose baclofen on cue reactivity in alcohol dependence: A
      randomized, placebo-controlled pharmaco-fMRI study.
AB  - Increased functional brain response towards alcohol-associated stimuli is a
      neural hallmark of alcohol dependence and a promising target for pharmacotherapy.
      For the first time, we assessed the effects of individually titrated high-dose
      baclofen on cue reactivity and functional connectivity in alcohol-dependent (AD)
      patients in a randomized controlled trial (RCT). We investigated 23 recently
      detoxified AD patients and 23 matched healthy controls (HC) with a cue reactivity
      functional magnetic resonance imaging task. Patients were further scanned at
      baseline without medication and during treatment with high-dose baclofen/placebo
      (30-270 mg/d). Analyses were conducted for alcohol cue-elicited brain response,
      alcohol cue-modulated and stimulus-independent functional connectivity with left
      ventral tegmental area (VTA) as seed region. At baseline, AD patients (N = 23)
      showed increased cue-elicited brain activation in the ventral striatum (VS)
      compared to HC (N = 23), which was decreased at the second scanning session
      compared to baseline. Patients receiving baclofen (N = 10) showed a significant
      stronger decrease in cue-elicited brain activation in left orbitofrontal cortex
      (OFC), bilateral amygdala and left VTA than patients receiving placebo (N = 13).
      Treatment with baclofen further led to a decrease in alcohol cue-modulated
      functional connectivity between left VTA and left anterior cingulate cortex (ACC)
      as well as left medial prefrontal cortex (MPFC). Regarding clinical outcome,
      significantly more patients of the baclofen group remained abstinent during the
      high-dose period. Baclofen specifically decreased cue-elicited brain responses in
      areas known to be involved in the processing of salient (appetitive and aversive)
      stimuli. Treatment with high-dose baclofen seems to provide a pharmacological
      relief of this neural "warning signal" evoked by alcohol-related cues, thereby
      possibly supporting patients in remaining abstinent. Trial Registration
      Identifier of the main trial [BACLAD study] at clinicaltrials.gov: NCT01266655.

PMID- 30217553
TI  - CB1 receptors in the paraventricular nucleus of the hypothalamus modulate the
      release of 5-HT and GABA to stimulate food intake in rats.
AB  - Endocannabinoids and their receptors not only contribute to the control of
      natural processes of appetite regulation and energy balance but also have an
      important role in the pathogenesis of obesity. CB1 receptors (CB1R) are expressed
      in several hypothalamic nuclei, including the paraventricular nucleus (PVN),
      where induce potent orexigenic responses. Activation of CB1R in the PVN induces
      hyperphagia by modulating directly or indirectly orexigenic and anorexigenic
      signals; however, interaction among these mediators has not been clearly defined.
      CB1R mRNA is expressed in serotonergic neurons that innervate the PVN, and
      activation of 5-HT receptors in the PVN constitutes an important satiety signal.
      Some GABAergic terminals are negatively influenced by 5-HT, suggesting that the
      hyperphagic effect of CB1R activation could involve changes in serotonergic and
      GABAergic signaling in the PVN. Accordingly, the present study was aimed to
      characterize the neurochemical mechanisms related to the hyperphagic effects
      induced by activation of CB1R in the PVN, studying in vitro and in vivo changes
      induced by direct activation these receptors. Here, we have found that the
      neurochemical mechanisms activated by stimulation of CB1 receptors in the PVN
      involve inhibition of 5-HT release, resulting in a decrease of serotonergic
      activity mediated by 5-HT1A and 5-HT1B receptors and inducing disinhibition of
      GABA release to stimulate food intake. In conclusion, these neurochemical changes
      in the PVN are determinant to the cannabinoid-induced stimulation of food intake.
      Our findings provide evidence of a functional connection among CB1R and
      serotonergic and GABAergic systems on the control of appetite regulation mediated
      by endocannabinoids.

PMID- 30217554
TI  - Intrapartum midwifery care impact Swedish couple's birth experiences - A cross
      sectional study.
AB  - BACKGROUND: Parents' birth experiences affect bonding with their infant, which in
      turn may influence the child's future health. Parents' satisfaction with
      childbirth is multi-dimensional and dependent on both expectations and
      experiences. Increasing involvement of partners in intrapartum care may lead to
      an assumption that the birthing couple shares attitudes and expectations of
      intrapartum care. There is a limited knowledge regarding the uniformity of
      couples' experiences of labour and birth. AIM: To describe and compare uniformity
      in couples' birth experiences of the quality of intrapartum midwifery care.
      METHOD: A quantitative cross-sectional study nested within a randomised
      controlled trial. In total 209 healthy primiparous mothers and their partners
      were recruited. A quality of care index was generated from an on-line
      questionnaire administered as a follow-up to the randomised controlled trial.
      Uniformity and differences were identified regarding the couples experiences of
      birth and their preferences for intrapartum care RESULTS: A high level of
      uniformity between the mothers and their partners was revealed. Birth was a
      positive experience for 79% of partners and 73% of mothers whom were more likely
      to have experienced a spontaneous vaginal birth. Partners and mothers with a less
      positive birth experienced deficiencies regarding: being in control, receiving
      information about labour progress and midwife's presence in labour room.
      DISCUSSION: Midwives can enhance couples' feeling of being in control during
      labour and birth by being attentive, present and continuously providing adequate
      information and emotional support.

PMID- 30217555
TI  - Diagnostic accuracy of interleukin-22 and adenosine deaminase for tuberculous
      pleural effusions.
AB  - OBJECTIVE: Reliable markers for accurately diagnosing tuberculous pleural
      effusions (TPE) are needed. This study sought to investigate the diagnostic
      potential of pleural interleukin-22 (IL-22) and compare it with the performance
      of adenosine deaminase (ADA). METHOD: This prospective study involved 49 patients
      with TPE and 60 patients with pleural effusion of other causes. Pleural levels of
      IL-22 and ADA were determined, respectively, using ELISA or an enzymatic method.
      A receiver operating characteristic curve was constructed and the area under the
      curve (AUC) was calculated to summarize the diagnostic accuracy of single markers
      or marker combinations. RESULTS: Levels of IL-22 in pleural effusion were
      significantly higher in TPE patients than in other patients (322.36 +/- 406.65
      vs. 83.13 +/- 22.15 pg/ml, P < 0.05). With a cut-off value of 97.82 pg/ml, the
      diagnostic sensitivity of IL-22 for TPE was 71.42%, specificity was 81.67%, and
      the area under the curve (AUC) was 0.83. ADA levels were also increased in TPE,
      and its AUC for diagnosing TPE was 0.90. The combination of IL-22 and ADA
      enhanced diagnostic accuracy, offering sensitivity of 83.67%, specificity of
      91.67%, and an AUC of 0.93. CONCLUSION: IL-22 may be useful for diagnosing TPE,
      and combining it with ADA may further enhance diagnostic accuracy. Our results
      justify more rigorous studies with larger samples to confirm the diagnostic
      potential of IL-22 for TPE.

PMID- 30217556
TI  - Automated, accurate, and three-dimensional method for calculating sagittal slope
      of the tibial plateau.
AB  - Increased posterior-inferior directed slope of the subchondral bone of the
      lateral tibial plateau is a risk factor for noncontact rupture of the anterior
      cruciate ligament (ACL). Previous measures of lateral tibial slope, however, vary
      from study to study and often lack documentation of their accuracy. These factors
      impede identifying the magnitude of lateral tibial slope that increases risk of
      noncontact ACL rupture. Therefore, we developed and evaluated a new method that
      (1) requires minimal user input; (2) employs 3D renderings of the tibia that are
      referenced to a 3D anatomic coordinate system; and (3) is precise, reliable, and
      accurate. The user first isolated the proximal tibia from computed tomography
      (CT) scans. Then, the algorithm placed the proximal tibia in an automatically
      generated tibial coordinate system. Next, it identified points along the rim of
      subchondral bone around the lateral tibial plateau, iteratively fit a plane to
      this rim of points, and, finally, referenced the plane to the tibial coordinate
      system. Precision and reliability of the lateral slope measurements were
      respectively assessed via standard deviation and intra- and inter-class
      correlation coefficients using CT scans of three cadaveric tibia. Accuracy was
      quantified by comparing changes in lateral tibial slope calculated by our
      algorithm to predefined in silico changes in slope. Precision, reliability, and
      accuracy were <=0.18 degrees , >=0.998, and <=0.13 degrees , respectively. We
      will use our novel method to better understand the relationship between lateral
      tibial slope and knee biomechanics towards preventing ACL rupture and improving
      its treatment.

PMID- 30217557
TI  - Doxycycline improves cage activity, but not exercised, supraspinatus tendon and
      muscle in a rat model.
AB  - The objective of this study was to investigate the effects of doxycycline, a
      broad-spectrum MMP inhibitor, on cage activity and exercised supraspinatus tendon
      and muscle using a Sprague-Dawley rat model of non-injurious exercise. Because
      exercise may alter muscle and tendon MMP activity and matrix turnover, we
      hypothesized that doxycycline would abolish the beneficial adaptations found with
      exercise but have no effect on cage activity muscle and tendon properties. Rats
      were divided into acute or chronic exercise (EX) or cage activity (CA) groups,
      and half of the rats received doxycycline orally. Animals in acute EX groups were
      euthanized 24 h after a single bout of exercise (10 m/min, 1 h) on a flat
      treadmill. Animals in chronic EX groups walked on a flat treadmill and were
      euthanized at 2 or 8 week time points. Assays included supraspinatus tendon
      mechanics and histology and muscle fiber morphologic and type analysis.
      Doxycycline improved tendon mechanical properties and collagen organization in
      chronic cage activity groups, which was not consistently evident in exercised
      groups. Combined with exercise, doxycycline decreased average muscle fiber cross
      sectional area. Results of this study suggest that administration of doxycycline
      at pharmaceutical doses induces beneficial supraspinatus tendon adaptations
      without negatively affecting the muscle in cage activity animals, supporting the
      use of doxycycline to combat degenerative processes associated with underuse;
      however, when combined with exercise, doxycycline does not consistently produce
      the same beneficial adaptations in rat supraspinatus tendons and reduces muscle
      fiber cross-sectional area, suggesting that doxycycline is not advantageous when
      combined with activity.

PMID- 30217559
TI  - Parallels between Mammalian Mechanisms of Monoallelic Gene Expression.
AB  - Different types of monoallelic gene expression are present in mammals, some of
      which are highly flexible, whereas others are more rigid. These include allelic
      exclusion at antigen receptor loci, the expression of olfactory receptor genes,
      genomic imprinting, X-chromosome inactivation, and random monoallelic expression
      (MAE). Although these processes play diverse biological roles, and arose through
      different selective pressures, the underlying epigenetic mechanisms show striking
      resemblances. Regulatory transcriptional events are important in all systems,
      particularly in the specification of MAE. Combined with comparative studies
      between species, this suggests that the different MAE systems found in mammals
      may have evolved from analogous ancestral processes.

PMID- 30217558
TI  - POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity
      during DNA Replication.
AB  - Maintenance of epigenetic integrity relies on coordinated recycling and
      partitioning of parental histones and deposition of newly synthesized histones
      during DNA replication. This process depends upon a poorly characterized network
      of histone chaperones, remodelers, and binding proteins. Here we implicate the
      POLE3-POLE4 subcomplex of the leading-strand polymerase, Polepsilon, in
      replication-coupled nucleosome assembly through its ability to selectively bind
      to histones H3-H4. Using hydrogen/deuterium exchange mass spectrometry and
      physical mapping, we define minimal domains necessary for interaction between
      POLE3-POLE4 and histones H3-H4. Biochemical analyses establish that POLE3-POLE4
      is a histone chaperone that promotes tetrasome formation and DNA supercoiling in
      vitro. In cells, POLE3-POLE4 binds both newly synthesized and parental histones,
      and its depletion hinders helicase unwinding and chromatin PCNA unloading and
      compromises coordinated parental histone retention and new histone deposition.
      Collectively, our study reveals that POLE3-POLE4 possesses intrinsic H3-H4
      chaperone activity, which facilitates faithful nucleosome dynamics at the
      replication fork.

PMID- 30217560
TI  - CD133-induced TM4SF5 expression promotes sphere growth via recruitment and
      blocking of protein tyrosine phosphatase receptor type F (PTPRF).
AB  - CD133 is a surface marker of liver cancer stem cells. Transmembrane 4 L six
      family member 5 (TM4SF5) promotes sphere growth and circulation. However, it is
      unknown how CD133 and TM4SF5 cross-talk with each other for cancer stem cell
      properties. Here, we investigated the significance of inter-relationships between
      CD133, TM4SF5, CD44, and protein tyrosine phosphatase receptor type F (PTPRF) in
      a three-dimensional (3D) sphere growth system. We found that CD133 upregulated
      TM4SF5 and CD44, whereas TM4SF5 and CD44 did not affect CD133 expression.
      Signaling activity following CD133 phosphorylation caused TM4SF5 expression and
      sphere growth. TM4SF5 bound to CD133 and promoted c-Src activity for CD133
      phosphorylation as a positive feedback loop, leading to CD133-mediated sphere
      growth that was inhibited by TM4SF5 inhibition or suppression. TM4SF5 also bound
      PTPRF and promoted paxillin phosphorylation. Decreased sphere growth upon CD133
      suppression was recovered by TM4SF5 expression and partially by PTPRF
      suppression. TM4SF5 inhibition enhanced PTPRF levels and abolished PTPRF
      suppression-mediated sphere growth. Altogether, CD133-induced TM4SF5 expression
      and function were important for liver cancer sphere growth and may be a promising
      target to block metastasis.

PMID- 30217561
TI  - KRAS targeting antibody synergizes anti-cancer activity of gemcitabine against
      pancreatic cancer.
AB  - Pancreatic cancer exhibits an oncogenic KRAS mutation rate of ~90%. Despite
      research and drug development efforts focused on KRAS, no targeted therapy has
      been clinically approved for the treatment of pancreatic cancer with KRAS
      mutation. Also, the efficacy of gemcitabine is poor due to rapidly acquired
      resistance. We developed RT11-i antibody, which directly targets the
      intracellularly activated GTP-bound form of oncogenic RAS mutants. Here, we
      investigated the combined effects of RT11-i and gemcitabine in vitro and in vivo,
      and the mechanism involved. RT11-i significantly sensitized pancreatic cancer
      cells to gemcitabine. Also, the co-treatment synergistically inhibited
      angiogenesis, migration, and invasion, and showed synergistic anticancer activity
      by inhibiting the RAF/MEK/ERK or PI3K/AKT pathways. Furthermore, co-treatment
      inhibited endothelial barrier disruption in tumor vessels, which is a critical
      step in vascular leakiness of metastasis, and improved vessel structural
      stability. Importantly, co-treatment significantly suppressed tumor growth in an
      orthotopic tumor model. Taken together, our findings show that RT11-i
      synergistically increased the antitumor activity of gemcitabine by inhibiting RAS
      downstream signaling, which suggests RT11-i and gemcitabine be viewed a potential
      combination treatment option for pancreatic cancer patients with KRAS mutation.

PMID- 30217562
TI  - The consensus on the monitoring, treatment, and prevention of leukemia relapse
      after allogeneic hematopoietic stem cell transplantation in China.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important
      curative therapy for patients with leukemia. However, relapse remains the leading
      cause of death after transplantation. In recent years, substantial progress has
      been made by Chinese physicians in the field of establishment of novel transplant
      modality, patient selection, minimal residual disease (MRD) monitoring, and
      immunological therapies, such as modified donor lymphocyte infusion (DLI) and
      chimeric antigen receptor T (CART) cells, as well as MRD-directed intervention
      for relapse. Most of these unique systems are distinct from those in the Western
      world. In this consensus, we reviewed the efficacy of post-HSCT relapse
      management practice from available Chinese studies on behalf of the HSCT
      workgroup of the Chinese Society of Hematology, Chinese Medical Association, and
      compared these studies withthe consensus or guidelines outside China. We
      summarized the consensus on routine practices of post-HSCT relapse management in
      China and focused on the recommendations of MRD monitoring, risk stratification
      directed strategies, and modified DLI system. This consensus will likely
      contribute to the standardization of post-HSCT relapse management in China and
      become an inspiration for further international cooperation to refine global
      practices.

PMID- 30217563
TI  - Immunogenic cell death in anticancer chemotherapy and its impact on clinical
      studies.
AB  - The traditional view holds that apoptosis is non-immunogenic and does not induce
      an inflammatory response. However, recent studies have suggested that certain
      chemotherapeutic drugs that induce tumor cell apoptosis can induce immunogenic
      cell death (ICD) in cancer cells. This process is characterized by not only up
      regulation of a series of signaling molecules in cancer cells, including expose
      of calreticulin (CRT), secretion of adenosine triphosphate (ATP) and release of
      high mobility group box 1 (HMGB1). In this review, we summarize recent progress
      in identifying and classifying ICD inducers; concepts and molecular mechanisms of
      ICD; and the impact and potential applications of ICD in clinical studies. We
      also discuss the contributions of ICD inducers in combination with other
      anticancer drugs in clinical applications.

PMID- 30217564
TI  - Upregulation of long non-coding RNA RAB1A-2 induces FGF1 expression worsening
      lung cancer prognosis.
AB  - The chromosomal locations of lncRNAs (long non-coding RNAs, lncRNAs) infer their
      biological functions in cancer. Lnc-RAB1A-2, a Ras-related protein Rab-1A (RAB1A)
      upstream lncRNA, was chosen for assessment of its impact on lung cancer prognosis
      in a case-based analysis and investigation of its biological function though a
      series of functional assays. Lnc-RAB1A-2 was significantly upregulated in 276
      lung cancer tissues compared with corresponding non-tumor tissues, and its
      expression level was significantly correlated with clinical stage and metastasis
      status in lung cancer patients. Patients with high expression levels of this
      lncRNA had a shorter median survival time (16.0 months vs. 23.0 months, P = 0.011
      in southern samples; 8.0 months vs. 19.0 months, P = 0.020 in eastern samples;
      13.0 months vs. 19.0 months, P = 0.002 in merged samples) and a higher risk of
      death than those with lower levels (HR = 1.52; 95% CI = 1.01-2.26, in merged
      samples). Additionally, overexpression of lnc-RAB1A-2 significantly promoted lung
      cancer cell proliferation in vitro and in vivo. Further analyses using digital
      gene expression tag profiling revealed that lnc-RAB1A-2 could affect the
      expression of fibroblast growth factor 1 (FGF1), a gene involved in the
      PI3K/AKT/mTOR pathway that is largely activated by RAB1A. FGF1 was confirmed to
      be a down-stream gene of lnc-RAB1A-2. Collectively, our study demonstrated that
      lnc-RAB1A-2 is associated with poor lung cancer prognosis by promoting lung
      cancer development.

PMID- 30217565
TI  - Context-dependent functions of KLF4 in cancers: Could alternative splicing
      isoforms be the key?
AB  - Kruppel-like factor 4 (KLF4) is an important transcription factor that is
      expressed in a variety of tissues and regulates many critical physiologic and
      cellular processes, including cell proliferation, differentiation, stem cell
      reprogramming, maintenance of genomic stability, and normal tissue homeostasis.
      KLF4 has both tumor suppressive and oncogenic functions in gastrointestinal and
      other cancers. These functions are thought to be context dependent, but how KLF4
      exerts these differential functions and the molecular mechanisms behind them
      remain poorly understood. Recent studies have shown that the KLF4 gene undergoes
      alternative splicing, and the protein products of certain transcripts antagonize
      wild-type KLF4 function, suggesting an additional layer of regulation of KLF4
      function. Therefore, detailed study of KLF4 alternative splicing may not only
      provide new insights into the complexity of KLF4 functions but also lead to
      rational targeting of KLF4 for cancer prevention and therapy.

PMID- 30217567
TI  - Lysosomes contribute to radioresistance in cancer.
AB  - Radiotherapy is one of the most widely used methods to treat human tumors.
      Efficacy is due mainly to the DNA damage it induces. However, tumor cells often
      develop responsive adaptiveness to radiation treatment to survive, which leads to
      radioresistance. Many cellular processes, such as DNA damage repair, cell cycle
      arrest and autophagy, are involved in the development of radioresistance. Few
      interventions to combat radioresistance exist to date. In recent years, the
      lysosome has been reported to contribute to chemo- and radioresistance. Although
      for many years, the lysosome was known as an organelle that degrades waste
      materials, we now know it is also involved in important signaling pathways
      regulating cellular homeostasis. Although an increasing number of preclinical
      studies show that lysosome-related factors promote radioresistance, the role of
      the lysosome in radioresistance has not been systematically demonstrated. Here,
      we combine an updated understanding of lysosomes with a review of current studies
      regarding the role of lysosomes in mediating radioresistance.

PMID- 30217568
TI  - Phosphorylation of androgen receptor serine 81 is associated with its
      reactivation in castration-resistant prostate cancer.
AB  - Phosphorylation of serine 81 (pS81) in the N-terminal transactivation domain of
      the androgen receptor (AR) has been linked to its transcriptional activation in
      prostate cancer (PCa) cell lines, but in vivo studies have been limited.
      Moreover, the role of pS81 in the reactivation of AR when tumors relapse after
      androgen deprivation therapy (castration-resistant prostate cancer, CRPC) has not
      been determined. In this study we validate a pS81 antibody for
      immunohistochemistry (IHC) and show it yields strong nuclear staining in primary
      PCa clinical samples and in the VCaP PCa xenograft model. Moreover, this staining
      was decreased at 7 days post-castration in VCaP xenografts, coinciding with
      markedly decreased AR transcriptional activity. Staining with the pS81 antibody
      then was restored when the VCaP xenografts relapsed, which was associated with
      restoration of AR transcriptional activity. Significantly, analysis of CRPC
      clinical samples, including tumors that had progressed during treatment with
      abiraterone, showed strong nuclear staining with the pS81 antibody. Together
      these findings indicate that AR reactivation in CRPC is associated with S81
      phosphorylation, and suggest that IHC for pS81 may be useful as a biomarker of AR
      activity in CRPC.

PMID- 30217566
TI  - Targeting the turnover of oncoproteins as a new avenue for therapeutics
      development in castration-resistant prostate cancer.
AB  - The current therapeutic armamentarium for castration-resistant prostate cancer
      (CRPC) includes second-generation agents such as the Androgen Receptor (AR)
      inhibitor enzalutamide and the androgen synthesis inhibitor abiraterone acetate,
      immunotherapies like sipuleucel-T, chemotherapies including docetaxel and
      cabazitaxel and the radiopharmaceutical radium 223 dichloride. However, relapse
      of CRPC resistant to these therapeutic modalities occur rapidly. The mechanisms
      of resistance to these treatments are complex, including specific mutations or
      alternative splicing of oncogenic proteins. An alternative approach to treating
      CRPC may be to target the turnover of these molecular drivers of CRPC. In this
      review, the mechanisms by which protein stability of several oncoproteins such as
      AR, ERG, GR, CYP17A1 and MYC, will be discussed, as well as how these findings
      could be translated into novel therapeutic agents.

PMID- 30217569
TI  - Adenovirus replication and host innate response in primary human airway
      epithelial cells.
AB  - BACKGROUND: Adenovirus infections are very common in children and sometimes
      fatal. Immune responses and hypercytokinemia are related to disease severity in
      patients with adenovirus infection. Understanding of viral replication and immune
      responses could help elucidate the immunopathogenesis of severe adenovirus
      infections. METHODS: Polarized human airway epithelial cells (hAECs) were set up
      to mimic human airway, and we conducted high (1 the multiplicity of infection,
      MOI) and low dosage (0.5 MOI) of wild-type adenovirus serotype 3 infection in
      hAECs from both apical (AP) and basolateral (BL) compartments, compared the viral
      replication kinetics and measured 25 cytokine and 9 chemokine levels by multiplex
      immunoassay to evaluate the host immune response. RESULTS: Virus titer was the
      highest in the apical compartment in low dose apical infection. BL infection
      showed a relative steady viral titer in different doses and infection sites.
      Responses of several cytokines such as IL-1RA, IL-21 and all of the chemokines
      were found after adenovirus infection. Besides, the responses detected in the BL
      compartment were generally higher than those in the apical compartment,
      especially IL-1RA, IL-21, GM-CSF, GRO-alpha, SDF-1alpha and IL-8. CONCLUSION:
      During the infections of hAECs by adenovirus, higher viral replication was found
      in the apical compartment but cytokine and chemokine responses were higher in the
      basolateral compartment. This indicated viral entrance and replication occurred
      more in the apical part and major innate response took place in the basolateral
      part, which may make adenovirus infect human airway efficiently and cause
      different degree of severity.

PMID- 30217570
TI  - Role of the endocannabinoid system in drug addiction.
AB  - Drug addiction is a chronic relapsing disorder that produces a dramaticglobal
      health burden worldwide. Not effective treatment of drug addiction is currently
      available probably due to the difficulties to find an appropriate target to
      manage this complex disease raising the needs for further identification of novel
      therapeutic approaches. The endocannabinoid system has been found to play a
      crucial role in the neurobiological substrate underlying drug addiction.
      Endocannabinoids and cannabinoid receptors are widely expressed in the main areas
      of the mesocorticolimbic system that participate in the initiation and
      maintenance of drug consumption and in the development of compulsion and loss of
      behavioral control occurring during drug addiction. The identification of the
      important role played by CB1 cannabinoid receptors in drug addiction encouraged
      the possible used of an early commercialized CB1 receptor antagonist for treating
      drug addiction. However, the incidence of serious psychiatric adverse events
      leaded to the sudden withdrawal from the market of this CB1 antagonist and all
      the research programs developed by pharmaceutical companies to obtain new CB1
      antagonists were stopped. Currently, new research strategies are under
      development to target the endocannabinoid system for drug addiction avoiding
      these side effects, which include allosteric negative modulators of CB1 receptors
      and compounds targeting CB2 receptors. Recent studies showing the potential role
      of CB2 receptors in the addictive properties of different drugs of abuse have
      open a promising research opportunity to develop novel possible therapeutic
      approaches.

PMID- 30217571
TI  - Role of the efflux transporters BCRP and MRP1 in human placental bio-disposition
      of pravastatin.
AB  - The expression and activity of human placental transporters during pregnancy
      could be altered by several factors including pathological changes associated
      with preeclampsia. The aims of this study were to identify the placental efflux
      transporters involved in the bio-disposition of pravastatin, determine the
      protein expression of these transporters and their encoding genes as well as the
      activity of pravastatin uptake in placentas obtained from patients with
      preeclampsia. ATP-dependent uptake of [3H]-pravastatin by trophoblast tissue
      apical and basal membrane vesicles exhibited sigmoidal kinetics. The curved
      shapes of Eadie-Hofstee plots indicate that more than one placental transporter
      are involved in the uptake of pravastatin. ATP-dependent uptake of [3H]
      pravastatin into vesicles expressing MRP1-5, BCRP, and P-gp, as well as the
      results of inhibition studies suggest that BCRP and MRP1 are the major placental
      efflux transporters responsible for the in vitro uptake of pravastatin. Compared
      to placentas from healthy pregnancies, preeclamptic placentas had increased
      number of syncytial knots with increased expression of BCRP in their apical
      membrane and increased expression of MRP1 in the cytoplasm of the
      syncytiotrophoblast and in cytoplasm of syncytial knots. There was a concomitant
      increase in ABCC1 but not in ABCG2 gene expressions in preeclamptic placentas.
      ATP-dependent uptake of [3H]-pravastatin by vesicles prepared from apical
      membranes of preeclamptic placentas was similar to the uptake by vesicles
      prepared from placentas obtained after uncomplicated pregnancies (13.9 +/- 6.5 vs
      14.1 +/- 5.8 pmol.mg protein-1 min-1). The transporter-specific changes in the
      expression of BCRP and MRP1 in preeclamptic placentas did not affect the efflux
      activity of transporters localized on the apical membrane of the
      syncytiotrophoblast.

PMID- 30217572
TI  - [Latent tuberculosis infection, from diagnosis to prognosis].

PMID- 30217573
TI  - [Corticosteroids in community acquired pneumonia: Where are we in 2018?]
AB  - Community-acquired pneumonia (CAP) is a common infectious disease and one of the
      main causes of mortality worldwide. Despite an improvement in management
      globally, mortality remains high especially in severe forms of CAP. Adequate
      early antibiotics remain the cornerstone of the treatment but adjuvant
      corticosteroid administration is being considered to counterbalance the systemic
      inflammatory reaction and modulate the immune response. In the last ten years,
      several clinical trials and meta-analyses have been conducted in severe and non
      severe CAP to assess the efficacy of corticosteroids. The benefits on the
      duration of hospitalization and the time to clinical stability are quite small
      and early mortality does not seem to be improved. Corticosteroids should not,
      therefore, be used routinely in patients with CAP, even in severe cases. However,
      new therapeutic trials are currently underway.

PMID- 30217574
TI  - [Interferon gamma release assays and immunosuppressive drugs (including biologic
      therapy)].

PMID- 30217575
TI  - [Interferon-gamma release assay tests in migrants].

PMID- 30217576
TI  - Analysis of the relationship among health awareness and health literacy, patient
      satisfaction levels with primary care in patients admitting to primary care
      health centers.
AB  - OBJECTIVE: The aim of the study was to examine the relationships between health
      literacy, primary care satisfaction levels and health awareness of the patients
      who were admitted to primary care centers (Family Health Centers). METHODS: This
      is a cross-sectional study conducted on individuals who were admitted to Family
      Health Centers (n = 1.055) in Eskisehir province. The study data were collected
      by using Turkish Health Literacy Scale, the European Patients Evaluate
      General/Family Practice Scale and Health Awareness Scale. RESULTS: As health
      literacy of participants increases, health awareness and satisfaction with
      primary care also increases (for each, p < .001). Health awareness increases
      health literacy by 0.55 points, health literacy increases satisfaction in primary
      care by 0.26 points. CONCLUSION: In the province of Eskisehir, the health
      literacy level of 7 out of 10 patients, who admitted to the primary care
      institution, is inadequate or problematic. As health awareness of participants
      increases, their level of health literacy also increases. As health literacy of
      participants increases, their satisfaction with family physicians also increases.
      PRACTICE IMPLICATIONS: As an integral part of preventive health services, studies
      should be performed to increase and improve the level of health literacy of
      patients who are admitted to primary care services.

PMID- 30217577
TI  - Testing Makes Us StrongerTM: Evaluating the correlation between exposure and
      intermediate outcomes targeted by the campaign's messages.
AB  - OBJECTIVES: To examine whether self-reported exposure to Testing Makes Us
      StrongerTM (TMUS), an HIV testing health communication campaign for black gay,
      bisexual, and other men who have sex with men (BMSM), was associated with key
      intermediate outcomes targeted by the campaign's messages. METHODS: Data from
      sexually active, HIV-negative or unknown status BMSM aged 18-44 (N = 590) were
      collected through an anonymous Web-based survey that measured sociodemographics,
      campaign exposure, attitudinal beliefs, normative beliefs, self-efficacy, and HIV
      testing intentions, among other variables. The association between exposure to
      TMUS and intermediate outcomes was evaluated using propensity-score weight
      adjusted correlations. RESULTS: Exposure to TMUS was high (43%) among the
      priority audience. Exposure to the campaign was correlated with 8 of 11
      intermediate outcomes measured, including key attitudinal beliefs about the
      accessibility of the test and benefits to the individual, injunctive norms, self
      efficacy, and HIV testing intention. CONCLUSION: Adhering to principles of
      effective campaign design, such as using theory as a conceptual foundation for
      message design, can increase a campaign's chances for successfully meeting its
      goals and objectives. PRACTICE IMPLICATIONS: Findings from this study can be used
      to inform message design for other communication efforts to promote HIV testing
      among BMSM.

PMID- 30217578
TI  - Donor heart preservation with a novel long-term and slow-releasing hydrogen
      sulfide system.
AB  - Cardiac transplantation has been limited by the inability to long preserve donor
      hearts safely. Hydrogen sulfide (H2S) has been recognized as an important
      gasotransmitter exerting potent cardioprotection from ischemia/reperfusion injury
      (I/R). Herein we investigated the cardioprotective effects of a novel long-term
      and slow-releasing H2S system, namely DATS-MSN, in heart preservation solution
      using a heart transplantation models. The release of H2S from DATS-MSN was slow
      and continuous in the University of Wisconsin solution (UW), correspondingly,
      DATS-MSN application demonstrated superior cardioprotective effects over the
      control and traditional H2S donors after 6 h heart preservation and 1 h
      reperfusion, associated with greater allograft performance including left
      ventricular developed pressure (LVDP) and dP/dt max, reduced plasmic CK-MB and
      troponin I levels, inhibited myocardial inflammation, increased antioxidant
      enzyme activities, preserved mitochondria structure and function, and decreased
      cardiomyocyte apoptosis index. Also, DATS-MSN application presented significant
      superiority in long-term allografts survival and function after 8 weeks of
      transplantation. In the in vitro experiments, cardiomyocytes injury from hypoxia
      was found to be relived with the treatment of DATS-MSN by anti-inflammatory
      effects via TLR4/NLRP3 pathway. The present work provides a long-term releasing
      H2S donor compatibly applied in the donor heart preservation, and preliminary
      explores its underlying mechanisms.

PMID- 30217579
TI  - Screening extremely obese pregnant women for obstructive sleep apnea.
AB  - BACKGROUND: Obesity is prevalent among pregnant women in the United States;
      obstructive sleep apnea is highly comorbid with obesity and is associated with
      adverse pregnancy outcomes. Screening for obstructive sleep apnea in pregnant
      women has remained a challenge because of a lack of validated screening tools.
      OBJECTIVE: The purpose of this study was to evaluate established obstructive
      sleep apnea screening tools, a sleepiness scale, and individual component items
      in a cohort of pregnant women with extreme obesity in mid pregnancy with the use
      of objective testing to determine obstructive sleep apnea status and to describe
      the prevalence of obstructive sleep apnea among women with extreme obesity. STUDY
      DESIGN: Adult pregnant subjects, between 24 and 35 weeks gestation, with a body
      mass index >=40 kg/m2 at the time of enrollment completed obstructive sleep apnea
      screening tools (Berlin Questionnaire, American Society of Anesthesiologists
      checklist, and STOP-BANG questionnaire) and the Epworth Sleepiness Scale; they
      also underwent physical examination of the neck, mouth, and airway. The published
      obstructive sleep apnea in pregnancy prediction score was calculated for each
      subject. Obstructive sleep apnea status for each subject was determined by the
      results of an overnight, unattended type III home sleep apnea test. RESULTS:
      Twenty-four percent of pregnant women with extreme obesity had obstructive sleep
      apnea on home sleep apnea testing in mid pregnancy (Apnea-Hypopnea Index, >=5
      events per hour]. Established obstructive sleep apnea screening tools performed
      very poorly to screen for obstructive sleep apnea in this cohort. Age, body mass
      index, neck circumference, frequently witnessed apneas, and highly likely to fall
      asleep while driving were associated most strongly with obstructive sleep apnea
      status in this cohort. CONCLUSION: We found that 24% of pregnant women with body
      mass index >=40 kg/m2 between 24 and 35 weeks gestation have obstructive sleep
      apnea, defined as Apnea-Hypopnea Index >=5 events per hour on an overnight type
      III home sleep apnea test. We found the Berlin Questionnaire, American Society of
      Anesthesiologists checklist, STOP-BANG, obstructive sleep apnea in pregnancy
      score by Facco et al, and the Epworth Sleepiness Scale were not useful screening
      tools for obstructive sleep apnea in a cohort of obese pregnant women. However,
      age, body mass index, neck circumference, frequently witnessed apneas, and likely
      to fall asleep while driving were associated with obstructive sleep apnea in this
      cohort. Further studies are needed to adjust the criteria and thresholds within
      the available screening tools to better predict obstructive sleep apnea in
      pregnant women with obesity.

PMID- 30217580
TI  - Long-term outcome of MR-guided focused ultrasound treatment and laparoscopic
      myomectomy for symptomatic uterine fibroid tumors.
AB  - BACKGROUND: Fibroid tumors are the most common benign tumors in women of
      reproductive age. Treatment is usually indicated for those who are symptomatic,
      with different techniques being used. OBJECTIVE: The purpose of this study was to
      compare the long-term outcome of laparoscopic myomectomy with magnetic resonance
      guided focused ultrasound for symptomatic uterine fibroid tumors. STUDY DESIGN: A
      cohort study was conducted on all patients with symptomatic uterine fibroid
      tumors who were admitted to a single tertiary care center and treated operatively
      with laparoscopic myomectomy or treated conservatively with magnetic resonance
      guided focused ultrasound from January 2012 until January 2017. Assessment for
      further interventions and sustained fibroid-associated symptoms was performed,
      with the use of the Uterine Fibroid Symptom and Quality of Life symptom severity
      score. RESULTS: One hundred fifty-four women met the inclusion criteria. Complete
      follow-up evaluation was achieved for 64 women who underwent laparoscopic
      myomectomy and for 68 women who were treated by magnetic resonance-guided focused
      ultrasound. Follow-up time was similar for the 2 groups (median, 31 months
      [interquartile range, 17-51 months] vs 36 months [interquartile range, 24-41];
      P=.95). The rate of additional interventions was 5 (7.8%) and 9 (13.2%),
      respectively (P=0.312). Similarly, the Uterine Fibroid Symptom and Quality of
      Life symptom severity score questionnaire score at follow-up interviews revealed
      comparable median scores of 17 (interquartile range, 12-21) vs 17 (interquartile
      range, 13-22) for laparoscopic myomectomy and magnetic resonance-guided focused
      ultrasound, respectively (P=.439). Analysis of each of the symptoms separately
      (bleeding, changes in menstruation, abdominal pain, bladder activity, nocturia,
      fatigue) did not change these findings, nor did a multivariate analysis.
      CONCLUSION: Satisfaction with long-term outcome and rate of reinterventions after
      magnetic resonance-guided focused ultrasound treatment or laparoscopic myomectomy
      for uterine fibroid tumors was comparable. Further larger randomized trials are
      needed to confirm these findings.

PMID- 30217581
TI  - Food and non-food reinforcement among pregnant women.
AB  - Excessive gestational weight gain (GWG) in pregnancy may be driven in part by
      greater motivation to eat, and studying the relative reinforcing value of food
      versus non-food commodities may provide insight into factors important for
      excessive GWG. This study was a cross-sectional examination of the relationship
      between women meeting the Institute of Medicine (IOM) guidelines for GWG and the
      relative reinforcing value of food vs. non-food commodities during pregnancy. Two
      hundred and thirty-three pregnant women (1st trimester, n = 44; 2nd trimester, n
      = 105; 3rd trimester, n = 84), aged 18-40, were recruited via a crowdsourcing
      platform and completed an online survey. Relative food reinforcement (RRVfood),
      relative non-food activity reinforcement (RRVactive) and relative non-food
      cognitively enriching activity reinforcement (RRVcognitive) were measured by a
      questionnaire at the point of contact. Self-reports of gestational age and weight
      gain during pregnancy were collected. The relationship between food and non-food
      reinforcement was assessed based on IOM classifications for weight gain during
      pregnancy. After adjustment for women's education level and parity, higher
      RRVfood (p = 0.036) and lower RRVcognitive (p = 0.040) responses were associated
      with greater GWG. Food reinforcing ratio (FRR) analysis was then conducted to
      systematically examine the effect of non-food behaviors on GWG when food
      reinforcement was accounted for. Women who gained below the IOM weight gain
      guidelines had significantly higher FRRcognitive than those gaining above (p =
      0.013), indicating cognitively enriching activities may better compete with food
      among pregnant women. Interventions that help to increase the reinforcing value
      of cognitively enriching activities may be a new avenue to regulate eating to
      minimize GWG.

PMID- 30217582
TI  - Use of 3-Dimensional Printing to Create Patient-Specific Abdominal Aortic
      Aneurysm Models for Preoperative Planning.
AB  - Fenestrated endovascular aortic repair (FEVAR) stent grafting is a minimally
      invasive procedure and an alternative to open surgical repair for abdominal
      aortic aneurysm repair, particularly with unideal neck anatomy. Planning and
      implementing a custom FEVAR graft is complicated, requiring advanced training and
      years of practice. As such, a method for creating a patient-specific, to-scale,
      cost-effective, 3-dimensional abdominal aortic aneurysm model for use in
      preoperative planning is presented. The model can be used to help physicians
      create custom FEVAR grafts, thus eliminating the currently used difficult and
      technical method for creating custom grafts. It also can assist physicians in
      visualizing and practicing their surgical approach for a specific patient.

PMID- 30217583
TI  - Hydroxocobalamin for the Treatment of Vasoplegia: A Review of Current Literature
      and Considerations for Use.

PMID- 30217584
TI  - Lung Isolation in the Setting of a Tracheostomy Stoma: Anesthesiologists Beware!

PMID- 30217585
TI  - Preemptive Analgesia: An Unobtainable Goal?

PMID- 30217586
TI  - Transthoracic Ventricular Septal Defect Closure in Children: An Evolving
      Treatment Strategy as an Alternative to Open Surgical Repair.

PMID- 30217587
TI  - Goal-Directed Oxygen Delivery During Cardiopulmonary Bypass: Can This Perfusion
      Strategy Improve Biochemical and Clinical Neurologic Outcomes?

PMID- 30217588
TI  - Ongoing Obstacles for Universal Use of Sedation for Transfemoral Transcatheter
      Aortic Valve Replacement.

PMID- 30217589
TI  - Biomacromolecules within bivalve shells: Is chitin abundant?
AB  - Bivalve shells are inorganic-organic nanocomposites whose material properties
      outperform their purely inorganic mineral counterparts. Most typically the
      inorganic phase is a polymorph of CaCO3, while the organic phase contains
      biopolymers which have been presumed to be chitin and/or proteins. Identifying
      the biopolymer phase is therefore a crucial step in improving our understanding
      of design principles relevant to biominerals. In this work we study seven shells;
      four are examples of nacroprismatic shells (Alathyria jacksoni, Pinctada maxima,
      Hyriopsis cumingii and Cucumerunio novaehollandiae), one homogeneous (Arctica
      islandica), and two are crossed lamellar (Callista kingii, Tridacna gigas). Both
      intact shells, their organic extracts as isolated after decalcification in acid,
      and the periostracum overlay have been studied by solid-state CP-MAS NMR, FTIR,
      SEM and chemical analysis. In none of the shells examined in this work do we find
      a significant contribution to the organic fraction from chitin or its derivatives
      despite popular models of bivalve biomineralization which assume abundant chitin
      in the organic fraction of mollusk bivalve shells. In each of the nacroprismatic
      extracts the 13C NMR spectra represent similar proteinaceous material, Ala and
      Gly-rich and primarily organized as beta-sheets. A different, yet highly
      conserved protein was found in the periostracum covering each of the three
      nacreous shells studied. The Arctica islandica shells with homogeneous
      microstructure contained proteins which do not appear to be silk-like, while in
      the crossed lamellar shells we extracted too little organic matter to
      characterize. STATEMENT OF SIGNIFICANCE: Hydrophobic macromolecules are
      structural components within the calcareous inorganic matrix of bivalve shells
      and are responsible for enhanced materials properties of the biominerals.
      Prevalent models suggest that chitin is such major hydrophobic component.
      Contrary to that we show that chitin is rare within the hydrophobic biopolymers
      which primarily consist of proteinaceous matter with structural motifs as silk
      like beta-sheets, or others yet to be determined. Recognizing that diverse
      proteinaceous motifs, devoid of abundant chitin, can yield the optimized
      mechanical properties of bivalve shells is critical both to understand the
      mechanistic pathways by which they regulate biomineralization and for the design
      of novel bioinspired materials.

PMID- 30217590
TI  - ECGI in atrial fibrillation: A clinician's wish list.
AB  - Have we a challenge of credibility in the invasive treatment of atrial
      fibrillation (AFIB)? The incidence of AFIB in the European Union (EU) is about
      600,000 cases per year, while only 100,000 get an invasive treatment with a
      failure rate of close to 40%. Those that remain in AFIB need two times more
      hospitalizations and three times more re-hospitalizations. AFIB accounts for over
      1% of the EU health care costs. Too many patients are not referred and the
      indication rates of cardiac ablation are inexplicably variable throughout the EU.
      A reflection is made on how electrocardiographic imaging (ECGI) can contribute to
      bringing the therapy to an advanced level by achieving a higher success rate,
      efficiently increasing access to ablation therapies, a better patient selection
      and therapy planning, personalization and follow up.

PMID- 30217591
TI  - Beyond Estrogen: Treatment Options for Hot Flashes.
AB  - Nonhormonal medications and complementary and alternative therapies are used by
      many women seeking relief from bothersome hot flashes. However, health care
      professionals may be less familiar with these treatment modalities. Although
      estrogen remains the most effective medication to reduce hot flashes, its
      potential harmful effects have led investigators to examine other treatments for
      hot flashes, and many women seek alternative forms of relief. Most of these
      trials are limited by a significant placebo effect, which frequently equals the
      effectiveness of the medication being evaluated. Despite this limitation,
      selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine
      reuptake inhibitors (SNRIs), and gabapentin have robust evidence for hot flash
      reduction. Each of these may be chosen for additional treatmenteffects that may
      benefit some women. Complementary and alternative medication trials are fraught
      with additional limitations, namely, a large placebo effect, greater homogeneity
      of participants, lack of validated tools, and lack of robust reporting of adverse
      effects. The data appear most robust for isoflavone supplementation, with overall
      hot flash reduction similar to the SSRIs, SNRIs, and gabapentin. Mindfulness
      based stress reduction therapy also has evidence of effectiveness and may be an
      ideal choice for some. Primrose oil, Chinese herbal medicine, acupuncture, and
      yoga have mixed results. The concerns related to hepatotoxicity preclude the use
      of black cohosh. Exercise, relaxation, and paced respiration have no proven
      benefit thus far in reducing hot flashes. Our goal with this commentary is to arm
      clinicians with information about the medications and complementary therapies
      available to provide symptom relief to women. Providing information about the
      possible benefits and harms of these therapies despite the limitations of the
      current evidence is helpful to patients and can help guide them to seek the
      treatment option most beneficial and appealing to them.

PMID- 30217592
TI  - The Role of Colchicine in Treating Postoperative and Post-Catheter Ablation
      Atrial Fibrillation.
AB  - PURPOSE: The goal of this review was to summarize, analyze, and compare trials
      studying the efficacy of colchicine in the prevention of atrial fibrillation (AF)
      post-operatively (POAF) and post-catheter ablation. Ongoing studies and current
      guidelines are also presented and reviewed. METHODS: Published studies on the
      field were identified through a literature search of the PubMed and
      clinicaltrials.gov databases. FINDINGS: Four original studies regarding POAF, two
      original studies regarding post-catheter ablation AF, and six meta-analyses were
      identified. In addition, the 3 most recent guidelines/expert consensus documents
      were scrutinized. IMPLICATIONS: AF occurs frequently after cardiac surgery (POAF)
      and catheter pulmonary vein isolation (postablation AF) and is associated with
      increased cardiovascular morbidity. A number of trials over the last few years
      have investigated the role of colchicine in the prevention of POAF and
      postablation AF targeting the local and systemic inflammatory process that leads
      to initiation and maintenance of AF. Available data imply that colchicine may
      have a preventive role in POAF and/or postablation AF. However, certain
      limitations of these studies underline the need for further investigation.

PMID- 30217593
TI  - Prevalence and risk factors for diabetes and impaired fasting glucose in
      Northeast China: Results from the 2016 China National Stroke Screening Survey.
AB  - AIMS: To explore the current prevalence and risk factors for diabetes and
      impaired fasting glucose in Northeast China. METHODS: This study adopted the
      multistage stratified random cluster sampling method to obtain a representative
      sample of adults aged 40 years or older in Dehui City, Jilin Province, Northeast
      China. Diabetes and impaired fasting glucose were defined according to the 1999
      World Health Organization criteria. RESULTS: A total of 4052 participants were
      included, with prevalence of diabetes in Northeast China of 11.2% (95% confidence
      interval [CI], 10.1-12.4%); that of diagnosed, 5.9% (95% CI, 5.1-6.8%); and that
      of impaired fasting glucose, 6.9% (95% CI, 6.0-8.0%). Among them, 52.9% were
      aware of their condition, 47.7% were receiving antidiabetic medication, and 75.9%
      had their diabetes controlled. Rural residents were more likely to have diabetes
      but were less inclined to be aware of and report antidiabetic treatment and to
      have their diabetes controlled than urban residents. CONCLUSION: Diabetes and
      impaired fasting glucose were highly prevalent among adults in Northeast China.
      However, awareness and treatment rates remained relatively low compared with
      those of developed countries. Health policymakers should put more basic medical
      and healthcare into rural areas in the future.

PMID- 30217594
TI  - Effect of metformin on exercise capacity: A meta-analysis.
AB  - AIMS: To evaluate the effect of metformin on various parameters of exercise
      capacity [oxygen consumption (VO2), peak oxygen consumption (VO2peak), heart rate
      (HR), exercise test duration, respiratory exchange ratio (RER), rating of
      perceived exertion (RPE), lactate and ventilatory anaerobic threshold (VAT)].
      METHODS: Studies reporting change in VO2 or VO2peak after metformin
      administration were included. Subgroup analyses were performed as applicable.
      Mean difference with 95% CIs were pooled using random-effects model [RevMan
      (v5.3)]. RESULTS: There were no changes in VO2 and VO2peak in the overall
      population [VO2: n = 388, mean difference: -0.12 ml/kg/min, 95% CI: -0.74, 0.51,
      p = 0.71 (i2 = 0%, p = 0.99); VO2peak: n = 345, mean difference: 0.41 ml/kg/min,
      95% CI: -0.51, 1.33, p = 0.38 (i2 = 0%, p = 0.89)], healthy volunteers and
      patients (type 2 diabetes mellitus, insulin resistance, impaired glucose
      tolerance/impaired fasting glucose and metabolic syndrome). For patients with
      insulin resistance, there was a decrease in VO2peak, but not VO2. In the overall
      population, there was a significant decrease in HR and RER, a significant
      increase in RPE, and no changes in exercise test duration and VAT. In addition,
      there was an increased VAT in the healthy volunteers. CONCLUSIONS: In the overall
      population, metformin did not affect VO2, VO2peak, exercise test duration and
      VAT, although it significantly decreased HR, RER and increased RPE.

PMID- 30217596
TI  - Sixty years of experimental studies on the blastogenesis of the colonial tunicate
      Botryllus schlosseri.
AB  - In the second half of the eighteenth century, Schlosser and Ellis described the
      colonial ascidian Botryllus schlosseri garnering the interest of scientists
      around the world. In the 1950's scientists began to study B. schlosseri and soon
      recognized it as an important model organism for the study of developmental
      biology and comparative immunology. In this review, we summarize the history of
      B. schlosseri studies and experiments performed to characterize the colony life
      cycle and bud development. We describe experiments performed to analyze
      variations in bud productivity, zooid growth and bilateral asymmetry (i.e., the
      situs viscerum), and discuss zooid and bud removal experiments that were used to
      study the cross-talk between consecutive blastogenetic generations and vascular
      budding. We also summarize experiments that demonstrated that the ability of two
      distinct colonies to fuse or reject is controlled by a single polymorphic gene
      locus (BHF) with multiple, codominantly expressed alleles. Finally, we describe
      how the ability to fuse and create chimeras was used to show that within a
      chimera somatic and germline stem cells compete to populate niches and regenerate
      tissue or germline organs. Starting from the results of these 60 years of study,
      we can now use new technological advances to expand the study of B. schlosseri
      traits and understand functional relationships between its genome and life
      history phenotypes.

PMID- 30217597
TI  - Development of the house secreting epithelium, a major innovation of tunicate
      larvaceans, involves multiple homeodomain transcription factors.
AB  - The mechanisms driving innovations that distinguish large taxons are poorly known
      and essentially accessible via a candidate gene approach. A spectacular
      acquisition by tunicate larvaceans is the house, a complex extracellular
      filtration device. Its components are secreted by the oikoplastic epithelium
      which covers the animal trunk. Here we describe the development of this
      epithelium in larvae through the formation of specific cellular territories known
      to produce distinct sets of house proteins (Oikosins). It involves cell divisions
      and morphological differentiation but very limited cell migration. A diverse set
      of homeobox genes, most often duplicated in the genome, are transiently and site
      specifically expressed in the trunk epithelium at early larval stages. Using RNA
      interference, we show that two prop duplicates are involved in the
      differentiation of a region on and around the dorsal midline, regulating
      morphology and the production of a specific oikosin. Our observations favor a
      scenario in which multiple homeobox genes and most likely other developmental
      transcription factors were recruited for this innovation. Their frequent
      duplications probably predated, but were not required for the emergence of the
      house.

PMID- 30217595
TI  - A spontaneous mouse deletion in Mctp1 uncovers a long-range cis-regulatory region
      crucial for NR2F1 function during inner ear development.
AB  - Hundreds of thousands of cis-regulatory DNA sequences are predicted in vertebrate
      genomes, but unlike genes themselves, few have been characterized at the
      functional level or even unambiguously paired with a target gene. Here we
      serendipitously identified and started investigating the first reported long
      range regulatory region for the Nr2f1 (Coup-TFI) transcription factor gene. NR2F1
      is temporally and spatially regulated during development and required for
      patterning and regionalization in the nervous system, including sensory hair cell
      organization in the auditory epithelium of the cochlea. Analyzing the deaf
      wanderer (dwnd) spontaneous mouse mutation, we traced back the cause of its
      associated circling behavior to a 53 kb deletion removing five exons and adjacent
      intronic regions of the poorly characterized Mctp1 gene. Interestingly, loss of
      Mctp1 function cannot account for the hearing loss, inner ear dysmorphology and
      sensory hair cell disorganization observed in dwnd mutants. Instead, we found
      that the Mctp1dwnd deletion affects the Nr2f1 gene located 1.4 Mb away,
      downregulating transcription and protein expression in the embryonic cochlea.
      Remarkably, the Mctp1dwnd allele failed to complement a targeted inactivation
      allele of Nr2f1, and transheterozygotes or Mctp1dwnd homozygotes exhibit the same
      morphological defects observed in inner ears of Nr2f1 mutants without sharing
      their early life lethality. Defects include improper separation of the utricle
      and saccule in the vestibule not described previously, which can explain the
      circling behavior that first brought the spontaneous mutation to attention. By
      contrast, mice homozygous for a targeted inactivation of Mctp1 have normal
      hearing and inner ear structures. We conclude that the 53 kb Mctp1dwnd deletion
      encompasses a long-range cis-regulatory region essential for proper Nr2f1
      expression in the embryonic inner ear, providing a first opportunity to
      investigate Nr2f1 function in postnatal inner ears. This work adds to the short
      list of long-range regulatory regions characterized as essential to drive
      expression of key developmental control genes.

PMID- 30217598
TI  - Developmental atlas of appendicularian Oikopleura dioica actins provides new
      insights into the evolution of the notochord and the cardio-paraxial muscle in
      chordates.
AB  - Locomotion by tail beating powered by a system of bilateral paraxial muscle and
      notochord is likely one of the key evolutionary innovations that facilitated the
      origin and radiation of chordates. The innovation of paraxial muscle was
      accompanied by gene duplications in stem chordates that gave rise to muscular
      actins from cytoplasmic ancestral forms, which acquired contractile capability
      thanks to the recruitment of the myosin motor-machinery. To better understand the
      role of actin diversification during the evolution of chordates, in this work we
      have characterized the complete actin catalogue of the appendicularian Oikopleura
      dioica, an urochordate that maintains a chordate body plan throughout its life,
      including the notochord in a muscled tail that confers an active free-living
      pelagic style. Our genomic survey, phylogenetic analyses and Diagnostic-Actin
      Values (DAVs) reveal that O. dioica has four muscular actins (ActnM1-4) and three
      cytoplasmic actins (ActnC1-3), most of which originated by independent gene
      duplications during the evolution of the appendicularian lineage. Detailed
      developmental expression atlas of the complete actin catalogue of O. dioica
      reveals differences in the temporal-regulation and tissue-specificity of
      different actin paralogs, suggesting complex processes of subfunctionalization
      during the evolution of urochordates. Our results suggest the presence of a
      "cardio-paraxial" muscular actin at least in the last common ancestor of
      Olfactores (i.e. vertebrates+urochordates). Our results reveal highly dynamic
      tissue-specific expression patterns for some cytoplasmic actins, including the
      notochord, ciliated cells and neurons with axonal projections, which challenge
      the classic housekeeping notion ascribed to these genes. Considering that
      previous work had demonstrated the existence of notochord-specific actins in
      cephalochordates, the tissue-specific expression of two cytoplasmic actins in the
      notochord of O. dioica suggests that this pattern plausibly reflects the
      ancestral condition of chordates, and provides new insights to better understand
      the evolutionary origin of the notochord.

PMID- 30217599
TI  - An efficient production of hybrid recombinant protein comprising non-structural
      proteins (NS 1 & NS 3) of bluetongue virus in prokaryotic expression system.
AB  - Strategic design and suitable purification techniques are of paramount importance
      in the production of recombinant proteins, if intended for use in a diagnostic
      assay. However, there is no single protocol that can be universally adopted for
      obtaining proteins in requisite quality and quantity across various platforms. In
      this study, we have targeted proteins of bluetongue virus (BTV), which is the
      causative agent of an arthropod-borne infectious disease in ruminants.
      Traditionally, serological diagnosis of the disease has rested upon either virus
      neutralization test or on an ELISA test that employed a recombinant structural
      (VP1, VP7) protein. Among the non-structural (NS) proteins of BTV, NS1 and NS3,
      are preferred candidate antigens in development of immuno-diagnostics as these
      provide the option for identifying recent/ongoing infection. However, the
      difficulty in production/purification of recombinant full length NS proteins of
      BTV in sufficient quantity and quality in various expression systems, due to
      inherent structural complexities, have restricted their wider applicability as
      immunodiagnostic reagents. To circumvent the difficulties associated with
      production/purification, we developed a novel NS1 and NS3 fusion gene (~1302 bp)
      encoding for NS1 N-terminus (1M to G252 aa) and NS3 protein containing the N- and
      C-termini with a deletion of two hydrophobic domains along with intervening
      variable central domain (118A to A182 aa) of bluetongue virus 23. This construct
      was cloned, over-expressed and efficiently purified by single step affinity
      chromatography under unique denaturing/renaturing condition. The purified fusion
      protein was found suitable for detection of antibodies against BTV in an indirect
      ELISA (iELISA).

PMID- 30217600
TI  - Biotechnological applications of elastin-like polypeptides and the inverse
      transition cycle in the pharmaceutical industry.
AB  - Proteins are essential throughout the biological and biomedical sciences and the
      purification strategies of proteins of interest have advanced over centuries.
      Elastin-like polypeptides (ELPs) are compound polymers that have recently been
      highlighted for their sharp and reversible phase transition property when heated
      above their lower critical solution temperature (LCST). ELPs preserve this
      behavior when fused to a protein, and as a result providing a simple method to
      isolate a recombinant ELP fusion protein from cell contaminants by taking the
      solution through the soluble and insoluble phase of the ELP fusion protein, a
      technique designated as the inverse transition cycle (ITC). ITC is considered an
      inexpensive and efficient way of purifying recombinant ELP fusion proteins. In
      addition, ELPs render recombinant fusion protein more stability and a longer
      clear time in blood stream, which give ELPs a lot of valuable applications in the
      biotechnological and pharmaceutical industry. This article reviews the
      modernizations of ELPs and briefly highlights on the possible use of technologies
      such as the automatic piston discharge (APD) centrifuges to improve the
      efficiency of the ITC in the pharmaceutical industry to obtain benefits.

PMID- 30217601
TI  - Comment on: Erlotinib in combination with bevacizumab has potential benefit in
      non small cell lung cancer: A systematic review and meta-analysis of randomized
      clinical trials.

PMID- 30217602
TI  - Altered FOXO1 activation in the programming of cardiovascular alterations by
      maternal diabetes.
AB  - Maternal diabetes programs cardiovascular alterations in the adult offspring but
      the mechanisms involved remain unclarified. Here, we addresed whether maternal
      diabetes programs cardiac alterations related to extracellular matrix remodeling
      in the adult offspring, as well as the role of forkhead box transcription factor
      1 (FOXO1) in the induction of these alterations. The heart from adult offspring
      from control and streptozotocin-induced diabetic rats was evaluated. Increased
      glycemia, triglyceridemia and insulinemia and markers of cardiomyopathy were
      found in the offspring from diabetic rats. In the heart, an increase in active
      FOXO1 and mRNA levels of its target genes, Mmp-2 and Ctgf, genes related to an
      altered extracellular matrix remodeling, together with an increase in collagen
      deposition and a decrease in the connexin43 levels, were found in the offspring
      from diabetic rats. Altogether, these results suggest an important role of FOXO1
      activation in the cardiac alterations induced by intrauterine programming in
      maternal diabetes.

PMID- 30217603
TI  - [Swept source optical coherence tomography for the monitoring of hypotony
      maculopathy after trabeculectomy].

PMID- 30217604
TI  - Lateral tarsal strip versus lateral tarsal strip with three-snip punctoplasty for
      managing epiphora in involutional ectropion.
AB  - PURPOSE: To compare the efficacy of two surgical techniques-lateral tarsal strip
      (canthoplasty) alone, and lateral tarsal strip with three-snip punctoplasty-in
      reducing epiphora arising from involutional ectropion with partial punctal
      stenosis. METHODS: Fourty patients with involutional ectropion and partial
      stenosis of the lacrimal punctum were randomly allocated to two treatment groups.
      Group 1 patients received lateral tarsal strip alone with only non-invasive
      stenting of the punctum, and group 2 patients received tarsal strip plus three
      snip punctoplasty. Subjective assessment of epiphora was achieved via completion
      of a quality of life (QoL) questionnaire preoperatively and at postoperative
      month 3. Eyelid position, adverse outcomes and corneal dryness (via Oxford
      grading scheme) were also assessed postoperatively. Only patients with unilateral
      problems were included in the study. RESULTS: Forty eyes of 40 patients were
      included: 20 in each group. The mean ages of group 1 and group 2 patients were
      79+/-11 and 80+/-9 years, respectively. All patients reported significantly
      reduced eye watering after surgery, with no significant intergroup difference in
      subjective outcomes, except that computer usage and night driving (P<0.05),
      improved in a more significant way in group 2. Eyelid malposition was corrected
      in all cases, there were no cases of postoperative punctal eversion, and no
      significant adverse events or complications occurred. Finally, the mean
      improvements in the dryness/keratitis score (using the Oxford scheme) were
      comparable between the 2 groups (P=0.34). CONCLUSION: The study findings indicate
      that treatment of involutional ectropion with partial punctal stenosis by lateral
      tarsal strip with three snip punctoplasty does not provide greater reduction in
      discomfort secondary to epiphora than conventional lateral tarsal strip alone,
      except for specific situations such as night driving or computer use.

PMID- 30217605
TI  - The role of tocilizumab in the treatment of inflammatory diseases of the eye and
      orbit: A useful alternative.
AB  - PURPOSE: With uveitis being one of the leading causes of blindness worldwide,
      biological therapies have arisen as an option for the treatment of refractory
      cases based on good results shown in clinical practice. The goal of this study is
      to provide a systematic review of current knowledge of the role and possible uses
      of tocilizumab in the field of ophthalmology. MATERIALS AND METHODS: We performed
      a search for records reporting the use of tocilizumab for various diseases in
      MEDLINE (PubMed and OVID). We conducted an analysis of several individual studies
      and their reported individual patient data (82 eyes of 45 patients) published
      from 2011 to 2017. CONCLUSIONS: Tocilizumab may prove to be an effective choice
      for the treatment of a variety of ocular conditions such as refractory uveitis,
      inflammatory macular edema, vitreo-retinal tumors and thyroid orbitopathy,
      leading to control of the inflammation in these patients. Further studies need to
      be conducted to establish its safety and efficacy.

PMID- 30217606
TI  - Central retinal artery occlusion in a young child secondary to resistance to
      activated protein C.

PMID- 30217608
TI  - Rifabutin-associated uveitis in a 10-year-old child with HIV: Case report and
      review of the literature.

PMID- 30217607
TI  - [Surgical management of strabismus in dysthyroid orbitopathy: A retrospective
      single-center study of 32 cases].
AB  - INTRODUCTION: Thyroid-related immune orbitopathy often results in a restrictive
      strabismus. We report our experience of surgical management in these cases.
      PATIENTS AND METHODS: We present a retrospective case series conducted on 32
      patients, operated between 2008 and 2017. Strabismus surgery was proposed in the
      postinflammatory stage with stable clinical findings for at least 6 months. It
      was performed under general anesthesia by recessions of restrictive muscles using
      a fixed suture technique. Outcomes were graded as excellent, good or poor,
      according to the presence or absence of diplopia in primary or reading positions,
      and according to whether prism prescription was necessary. RESULTS: The study
      included 32 patients (21 women, 11 men) with a mean age of 53 years. Average
      follow-up was 9.6 months. Eight patients developed diplopia after orbital
      decompression. Fifteen patients had vertical surgery, 8 horizontal surgery, 9
      mixed surgery. A mean of 1.31 surgeries (range 1-3) were performed. After all
      surgeries, 28 patients (87.5 %) had an excellent outcome, 4 (12.5 %) had a good
      outcome, and none had a poor outcome. There was a significant improvement in
      stereoscopic acuity (P<0.01), but not motility. Among the 8 patients who
      developed diplopia after orbital decompression, a clinically acceptable final
      outcome was achieved after only one surgery. CONCLUSION: Strabismus surgery using
      conventional non-adjustable sutures provides excellent ocular alignment and
      relief from diplopia in the majority of patients with dysthyroid strabismus. The
      reoperation rate is similar to other techniques, such adjustable suture and
      intraoperative relaxed muscle technique.

PMID- 30217609
TI  - Central serous chorioretinopathy: Professional repercussions among agents of the
      internal security forces.
AB  - PURPOSE: To describe the relationship between central serous chorioretinopathy
      (CSCR) and stress in addition to the transient and permanent professional
      repercussions of this condition among security forces agents. MATERIAL AND
      METHODS: This is a retrospective, descriptive study of 22 CSCR patients. All
      patients were interviewed to establish their job status, a stressful triggering
      event, the number of consultations, absenteeism, the duration of episodes, the
      number of days off, exemption from certain activities and professional
      reclassification. All of our patients underwent a complete ophthalmological
      examination and ancillary testing (OCT optical coherence tomography, fluorescein
      retinal angiography) to establish the positive diagnosis and to determine the
      clinical form. RESULTS: During their daily activity, all patients were armed and
      worked night security duty. They all reported a stressful event just before the
      onset of the disease. The average visual acuity was 4/10 P6 all forms combined;
      with a visual acuity between 1 and 2/10 for the chronic form. Visual impairment
      was associated with absenteeism (mean length of time off was 1.13 months per
      episode), exemptions from carrying arms or night duty in 36.36% of cases, with
      professional reclassification in 22.7% of patients. CONCLUSION: CSCR affects
      psychology and alters the quality of life of patients who are generally young and
      professionally active. This can interfere with work performance and cause
      temporary or permanent disability.

PMID- 30217611
TI  - [Bilateral dendritic keratitis].

PMID- 30217610
TI  - [Assessment of astigmatism associated with the iris-fixated ARTISAN aphakia
      implant: Anterior fixation versus posterior fixation, study of postoperative
      follow-up at one year].
AB  - PURPOSE: The goal of our retrospective, single-center study of a case series was
      to compare the total, corneal, and internal astigmatism, and the visual acuity at
      one year after combined or stand-alone surgery consisting of iris fixation of an
      iris-claw intraocular lens (ARTISAN aphakia) in aphakic patients, according to
      whether the lens was fixated to the anterior (n=21) or posterior (n=51) surface
      of the iris. RESULTS: We did not find a significant difference between these two
      types of fixation for any of the studied variables. The surgically induced
      astigmatism was 1.67 D at 176 degrees  in group A versus 1.19 D at 11 degrees  in
      group P. CONCLUSION: Although this surgery creates additional corneal
      astigmatism, it has not been proven that it differs depending on the type of
      fixation of the iris-claw. If we adhere to the notion that the posterior fixated
      iris-claw decreases the risk of endothelial decompensation in case the implant
      becomes disenclavated, then reverse iris fixation of the iris-claw makes sense.

PMID- 30217612
TI  - [Invasive squamous cell carcinoma of the cornea treated with mitomycin eye
      drops].

PMID- 30217613
TI  - [Evaluation by quality of life questionnaires in patients undergoing strabismus
      surgery in Graves' disease].
AB  - PURPOSE: To evaluate the improvement in quality of life of patients operated
      within 6 months for strabismus in Graves' disease using a questionnaire.
      MATERIALS AND METHODS: A retrospective study was based on a cohort of patients
      undergoing strabismus surgery for Graves' disease at the Nancy university medical
      center between June 2015 and January 2017. A quality-of-life questionnaire
      composed of the functional GO QOL questionnaire plus 10 additional questions was
      given to patients. The questionnaires were completed by patients in consultation
      before surgery and then at six months postoperatively. A subgroup analysis was
      conducted to identify potential risk factors such as smoking, orbital
      decompression, duration of disease progression, number of surgeries, previous
      treatments or gender influences on the progression of the postoperative score.
      RESULTS: Thirty-three patients (15 men/18 women) underwent surgery, with mean age
      56 years; 16 (48 %) were smokers, 24 (70 %) were operated for the first time for
      strabismus. 8 patients (24 %) had a history of surgical orbital decompression.
      The mean preoperative GO QOLf was 30 (+/-23.8), which increased to 72 (+/-29.6)
      postoperatively (P=0.004). All the answers to the questions proposed were
      improved by surgery. The most improved items were difficulty in extreme gaze+6.82
      points (P=0.001) and going down stairs +6.81 (P=0.002). Smokers had a lower
      preoperative GO QOLf than non-smokers (25+/-22.84 vs. 34+/-24.55); the same was
      true for their postoperative improvement (35+/-34.5 points vs. 50+/-18.8,
      P=0.002). History of orbital decompression did not appear to influence quality of
      life (21+/-25.39 vs. 65+/-33.98); the same was true for previous corticosteroid
      or immunosuppressant treatment (28+/-23.52 vs. 67+/-28.24), respectively P=0.42;
      P=0.73. Gender did not appear to influence the results P=0.17. First-time
      strabismus surgery patients showed a tendency which was not significant toward
      better improvement after 2 or 3 surgeries (respectively 45 vs. 39 vs. 33)
      P=0.056. There was no correlation between the duration of the disease and the
      change in the GO QOLf (R=0.04). CONCLUSION: This study confirms that strabismus
      surgery significantly improves the quality of life of patients with Graves'
      ophthalmopathy. The GO QOLf demonstrates its effectiveness in highlighting this
      progression. Our ten additional questions proved to be very good tools for
      assessing this condition.

PMID- 30217615
TI  - Collagen type I degradation fragments act through the collagen receptor LAIR-1 to
      provide a negative feedback for osteoclast formation.
AB  - The major organic component of bone is collagen type I. Osteoclasts are
      terminally differentiated multinucleated cells of hematopoietic origin that are
      essential for physiological development of bone and teeth. We examined if
      osteoclast differentiation from murine bone marrow precursors is affected by
      collagen type I, or by its degradation products produced by human recombinant
      cathepsin K. Osteoclasts formation was dose-dependently inhibited in the presence
      of full length collagen type I or its 30-75 kDa degradation products added to the
      osteoclast differentiation media for the duration of an experiment. Collagen
      degradation fragments signaled through SH-2 phosphatases, inhibiting calcium
      signaling and NFATc1 translocation in osteoclast precursors. Osteoclasts and
      their precursors expressed a collagen receptor of leukocyte receptor complex
      family, LAIR-1. Importantly, collagen fragments failed to inhibit osteoclast
      formation from LAIR-1 deficient murine osteoclast precursors. This study
      demonstrates that collagen degradation fragments inhibit osteoclast formation
      acting through LAIR-1, providing a novel mechanism for the physiologically
      relevant negative control of osteoclastogenesis.

PMID- 30217614
TI  - Long-term interaction between Drosophila sperm and sex peptide is mediated by
      other seminal proteins that bind only transiently to sperm.
AB  - Seminal fluid proteins elicit several post-mating physiological changes in mated
      Drosophila melanogaster females. Some of these changes persist for over a week
      after mating because the seminal protein that causes these changes, the Sex
      Peptide (SP), binds to sperm that are stored in the female reproductive tract.
      SP's sperm binding is mediated by a network of at least eight seminal proteins.
      We show here that some of these network proteins (CG1656, CG1652, CG9997 and
      Antares) bind to sperm within 2 h of mating, like SP. However, while SP remains
      bound to sperm at 4 days post-mating, none of the other network proteins are
      detectable at this time. We also observed that the same network proteins are
      detectable at 2 h post-mating in seminal receptacle tissue from which sperm have
      been removed, but are no longer detectable there by 4 days post-mating,
      suggesting short-term retention of these proteins in this female sperm storage
      organ. Our results suggest that these network proteins act transiently to
      facilitate the conditions for SP's binding to sperm, perhaps by modifying SP or
      the sperm surface, but are not part of a long-acting complex that stably attaches
      SP to sperm.

PMID- 30217616
TI  - Bortezomib-based Chemotherapy for Multiple Myeloma Patients Without Comorbid
      Cardiovascular Disease Shows No Cardiotoxicity.
AB  - BACKGROUND: Proteasome inhibitors used in the treatment of multiple myeloma act
      primarily through the disruption of intrinsic cellular protein quality
      maintenance, resulting in proteotoxic stress, cellular dysfunction, and,
      ultimately, cell death. We assessed whether evidence has shown off-target
      myocardial dysfunction related to the administration of bortezomib-based
      chemotherapy for multiple myeloma. PATIENTS AND METHODS: Patients aged 18 to 70
      years who were free of significant cardiovascular disease were included. They
      underwent evaluations before and after each dose of bortezomib to assess for
      clinical, subclinical, and transient cardiotoxicity using echocardiography and
      serum biomarker measurement. Cardiac magnetic resonance imaging was performed at
      3 separately defined intervals. The primary modality for determining subclinical
      myocardial dysfunction was echocardiographic assessment of the global
      longitudinal strain (GLS). RESULTS: Eleven patients (7 men) with an average age
      of 55 years were included. No evidence of cumulative myocardial dysfunction was
      found using echocardiographic markers, primarily GLS (average change in absolute
      GLS, -1.17; P = .064). Additionally, no echocardiographic evidence of transient
      cardiotoxicity was found. The left ventricular ejection fraction (LVEF) also did
      not show any significant changes (DeltaLVEF, -2.17%; P = .15). Magnetic resonance
      imaging confirmed no changes in structure or function (DeltaLVEF, -2.6%; P = .54)
      and extracellular volume fraction (Delta = 2%; P = .46). The serum biomarker
      levels also did not change significantly over time. CONCLUSION: We did not
      observe cardiotoxicity from bortezomib-based chemotherapy despite very intensive
      evaluation with multiple modalities. Neither cumulative nor transient alterations
      were found in our metrics, suggesting that bortezomib is safe from a
      cardiovascular standpoint for patients free of cardiovascular disease.

PMID- 30217617
TI  - Oncological outcomes of early glottic carcinoma treated with transoral robotic
      surgery.
AB  - OBJECTIVE: Although glottic level is an off-label use of da Vinci system, the
      feasibility and early-term outcomes of transoral robotic surgery (TORS) for the
      treatment of early-stage (Tis, T1, T2) glottic carcinoma have been documented.
      But little is known about the oncological outcomes. We investigated the
      oncological outcomes of TORS in patients followed at least three years and mean
      follow-up time was over five years. METHODS: We retrospectively investigated
      patients with early glottic carcinoma (Tis, T1, T2) who underwent TORS cordectomy
      in a tertiary hospital between January 2010 and June 2018. RESULTS: Forty-eight
      patients were enrolled in the study. Mean follow-up time was 65.6+/-16.6months.
      Only one patient died and overall survival rate was found 97.9%. Local recurrence
      occurred in five patients and disease free survival rate was found 89.6%.
      Anterior commissure involvement was occurred in 6 (12.5%) patients and local
      recurrence was seen two of them (33.3%). Synechia complication was occurred in 8
      (16.7%) patients and local recurrence was seen three of them (36.7%). Although
      local recurrence rate was high in both anterior commissure involvement and
      synechia, only synechia reached to statistical significance for local recurrence
      (p: 0.027). The recurrences of four patients were treated with radiation therapy
      (RT) and the remaining one patient underwent total laryngectomy. Laryngeal
      preservation rate was found 97.9%. CONCLUSION: Our investigation of the
      oncological outcomes of TORS on early-stage glottic carcinoma revealed that TORS
      has similar results when compared with transoral laser microsurgery and RT in
      terms of recurrence, laryngeal preservation and survival rates. Synechia is also
      a cautionary complication for recurrence and must be followed closely. We expect
      that TORS usage will be wider if robotic technology works on innovative
      developments oriented to glottic area.

PMID- 30217618
TI  - Missed Opportunities in the Outpatient Pediatric Setting to Support
      Breastfeeding: Results From a Mixed-Methods Study.
AB  - INTRODUCTION: Outpatient pediatric providers play a crucial role in the promotion
      of breastfeeding. We conducted a mixed methods study to measure provider
      knowledge, attitudes, and current practices around breastfeeding counseling.
      METHOD: In New Mexico in 2016 and 2017, we conducted a knowledge, attitudes, and
      practice survey of outpatient pediatric providers (i.e., nurse practitioners,
      physicians, and physician assistants) and conducted focus groups with outpatient
      pediatric providers. RESULTS: Seventy-seven providers responded to the survey,
      and 17 participated in three focus groups. Fewer than half of providers surveyed
      reported asking how long mothers plan to breastfeed at initial well-baby
      examinations. One quarter of participants (28.2%) erroneously reported that
      hepatitis C was an absolute contraindication to breastfeeding. Just half of
      respondents had received continuing education within the past 3years about
      managing common breastfeeding problems. DISCUSSION: We identified missed
      opportunities for outpatient pediatric providers to support breastfeeding and a
      need for continuing provider education.

PMID- 30217619
TI  - Proven immunologically-mediated drug hypersensitivity in children with a history
      of multiple drug intolerances.
AB  - BACKGROUND: Children may be referred to pediatric allergy clinics for reactions
      to multiple drugs. Multiple drug hypersensitivity (MDH) is defined as
      immunologically-mediated hypersensitivity to 2 or more chemically different
      drugs. OBJECTIVE: The aim of this study is to report the allergy workup results
      of children who had a history of potential hypersensitivity reactions to 2 or
      more unrelated drugs. METHODS: This study was conducted in the Pediatric Allergy
      and Immunology department of our hospital. Children who described
      hypersensitivity reactions to 2 or more drugs were included and were evaluated by
      allergy workup (skin and/or provocation tests) between January 2011 and July
      2016. RESULTS: During the study period, 886 children were evaluated for a history
      of drug intolerance. Of these children, 73 (8.2%) had a history of drug reactions
      to 2 or more chemically different drugs. The median age of the children who had a
      history of reactions to 2 or more drugs was 7.8 (min-max: 2.5-16.4) years, and
      59% (n = 43) were male. Among the suspected drugs, antibiotics (65.9%) ranked
      first, and nonsteroid anti-inflammatory drugs (34.1%) were the second. All 73
      children were evaluated with skin or provocation tests with the suspected drugs,
      and MDH was confirmed in only 2 (2.7%) children. CONCLUSION: Multiple drug
      hypersensitivity is uncommon in children. The incidence and prevalence of MDH may
      vary with the specific population studied. Evaluating children with a history of
      MDH, by performing drug hypersensitivity testing, will help avoid the morbidity
      associated with unnecessary drug avoidance.

PMID- 30217620
TI  - Fatty acids in pregnancy and risk of allergic sensitization and respiratory
      outcomes in childhood.

PMID- 30217621
TI  - Coronary artery bypass graft surgery complications: A review for emergency
      clinicians.
AB  - INTRODUCTION: Coronary artery bypass graft (CABG) surgery remains a high-risk
      procedure, and many patients require emergency department (ED) management for
      complications after surgery. OBJECTIVE: This narrative review provides an
      evidence-based summary of the current data for the emergency medicine evaluation
      and management of post-CABG surgery complications. DISCUSSION: While there has
      been a recent decline in all cardiac revascularization procedures, there remains
      over 200,000 CABG surgeries performed in the United States annually, with up to
      14% of these patients presenting to the ED within 30 days of discharge with post
      operative complications. Risk factors for perioperative mortality and morbidity
      after CABG surgery can be divided into three categories: patient characteristics,
      clinician characteristics, and postoperative factors. Emergency physicians will
      be faced with several postoperative complications, including sternal wound
      infections, pneumonia, thromboembolic phenomena, graft failure, atrial
      fibrillation, pulmonary hypertension, pericardial effusion, strokes, renal
      injury, gastrointestinal insults, and hemodynamic instability. Critical patients
      should be evaluated in the resuscitation bay, and consultation with the primary
      surgical team is needed, which improves patient outcomes. This review provides
      several guiding principles for management of acute complications. Understanding
      these complications and an approach to the management of hemodynamic instability
      is essential to optimizing patient care. CONCLUSIONS: Postoperative complications
      of CABG surgery can result in significant morbidity and mortality. Physicians
      must rapidly diagnose these conditions while evaluating for other diseases. Early
      surgical consultation is imperative, as is optimizing the patient's hemodynamics,
      including preload, heart rate, cardiac rhythm, contractility, and afterload.

PMID- 30217623
TI  - Thymic epithelial neoplasms with Rhabdomyomatous component: a Clinicopathological
      and Immunohistochemical study of 7 cases.
AB  - Seven primary thymic epithelial neoplasms, three thymomas, and four thymic
      carcinomas with rhabdomyomatous component are herein described. The patients are
      two women and 5 men between the ages of 42 and 62years (average: 52years).
      Clinically, the patients presented with non-specific symptoms of cough, chest
      pain, and dyspnea. None of the patients had history of myasthenia gravis or of
      previous malignancy. Diagnostic imaging revealed the presence of an anterior
      mediastinal mass in all the patients. Surgical resection was accomplished in all
      the cases. The three thymoma cases were encapsulated tumors: histologically two
      were lymphocyte rich (WHO type B1) and one was an atypical thymoma (WHO type B3).
      All the thymic carcinomas were ill-defined tumor masses with infiltrative borders
      and histologically were high grade carcinomas. In each tumor, in different
      proportion, there were easily identifiable areas with rhabdomyomatous component
      characterized by larger cells with eosinophilic cytoplasm and eccentrically
      placed nuclei. Immunohistochemical stains in all cases showed clearly demarcated
      presence of the epithelial component (keratin positive / desmin and myoglobin
      negative) and the rhabdomyomatous component (desmin and myoglobin positive /
      keratin negative). The three patients with thymoma are alive and without
      recurrence 3 and 5years after surgical resection, while three patients with
      carcinoma died between 2 and 3years post-surgical resection. One patient with
      thymic carcinoma was lost to follow-up. The current cases highlight the
      ubiquitous distribution of myoid cells in different types of thymic epithelial
      neoplasms.

PMID- 30217622
TI  - Histopathologic tumor regression grading in patients with gastric carcinoma
      submitted to neoadjuvant treatment: results of a Delphi survey.
AB  - Studies investigating the histopathologic response of gastric carcinoma to
      neoadjuvant treatment have used a variety of different tumor regression grading
      systems. The aim of this Delphi survey was to review the available systems and
      reach consensus on a potential international standard. An international email
      based Delphi survey involving six expert pathologists was undertaken between
      January and October 2017. A questionnaire consisting of seventy-two items was
      formed after reviewing the five available systems. Rating of the items was done
      on a symmetric 4-point Likert-type scale and feedback was provided between
      rounds. A total of four rounds were required to reach consensus on 97% of the
      items covering the topics: (1) Specimen processing, (2) Gross examination, (3)
      Cross-sectioning / method of sampling, (4) Staining, (5) Immunohistochemistry,
      (6) Assessment of tumor regression in response to neoadjuvant therapy, (7) Tumor
      regression grading, (8) Assessment of regression of nodal metastases and (9) Role
      of histological tumor type. Through the outcome of this comprehensive Delphi
      study, a group of experts is proposing a 4-tiered system for the grading of
      regression of the primary tumor, combined with a 3-tiered system for lymph node
      metastases. Grade 1 represents complete response, grade 2 contains <10% residual
      tumor (subtotal regression), grade 3 10-50% residual tumor (partial regression)
      and grade 4>50% residual tumor (minimal/no regression). The addition of "a", "b"
      or "c" indicates complete, partial or no response of lymph node metastases. It is
      recommended to use this grading system irrespective of histologic subtype.

PMID- 30217624
TI  - Subclavian Vein Aneurysm.

PMID- 30217625
TI  - Single nucleotide polymorphism array analysis uncovers a large, novel duplication
      in Xq13.1 in a floppy infant syndrome patient.
AB  - OBJECTIVE: To identify candidate genes for the clinical diagnosis of floppy
      infant syndrome (FIS) using single nucleotide polymorphism (SNP) array in a
      specific FIS family. METHODS: SNP array analysis of the whole chromosome copy
      number was performed in the proband (III1). Multiple polymerase chain reaction
      (PCR) combined with denaturing high-performance liquid chromatography (DHPLC) was
      used to validate the array data. RESULTS: A large 5.818182 Mb duplication
      (Xq13.1: 67987646-73805828), which encompasses 66 known genes, was found in III1.
      The start and end points of the duplication were confirmed with an SNP array.
      Duplicated genes with potential roles in central and/or peripheral nervous system
      development (HDAC8, PHKA1, TAF1, DLG3, KIF4A, IGBP1, PJA1, and SLC16A2) were
      confirmed by multiple PCR-DHPLC in III1. The patient's mother and grandmother
      carry duplications in these eight genes, but only on one X chromosome, while the
      patient's aunt does not carry any of the duplications. CONCLUSION: Based on the
      location of the eight candidate genes in Xq13.1, the large duplication found by
      SNP array does indeed exist and is predicted to be both novel and pathogenic.
      Moreover, we recommend SNP array as the first option for genetic diagnosis of
      both large-scale and rare/complicated diseases, such as FIS.

PMID- 30217626
TI  - Coronary perfusion pressure and left ventricular hemodynamics as predictors of
      cardiovascular collapse following percutaneous coronary intervention.
AB  - BACKGROUND/PURPOSE: Appropriate patient selection for mechanical circulatory
      support following percutaneous coronary intervention (PCI) remains a challenge.
      This study aims to evaluate the role of coronary perfusion pressure and other
      left ventricular hemodynamics to predict cardiovascular collapse following PCI.
      METHODS/MATERIALS: We retrospectively analyzed all patients who underwent PCI for
      acute coronary syndrome (ACS) from 2003 to 2016. Coronary perfusion pressure was
      calculated for each patient and defined as the difference in mean arterial
      pressure and left ventricular end diastolic pressure (LVEDP). Logistic regression
      analysis was performed to determine predictor of composite outcome of in-hospital
      mortality, myocardial infarction (MI), congestive heart failure (CHF), and
      cardiogenic shock. RESULTS: Nine hundred twenty-two patients were analyzed. Two
      hundred twenty-eight (25%) presented with ST-elevation MI (STEMI) while 694 (75%)
      underwent PCI for unstable angina or non-Q-wave MI. The mean LVEDP was
      significantly higher in the STEMI patients (24 +/- 9 vs. 19 +/- 8 mm Hg, p <
      0.05) and perfusion pressure significantly lower (68 +/- 24 vs. 74 +/- 18 mm Hg,
      p < 0.05). Eighty-seven (9.4%) reached the composite endpoint, and there was no
      difference between the STEMI and Not-STEMI groups. Neither LVEDP nor coronary
      perfusion pressure was a predictor of the composite outcome following
      multivariable logistic regression analysis for either STEMI or Not-STEMI
      patients. Increasing age, chronic renal insufficiency (CRI), CHF, and low left
      ventricular ejection fraction were predictors of the composite outcome for Not
      STEMI patients, whereas only history of cerebrovascular accident and CRI were
      predictors for STEMI patients. CONCLUSIONS: In hemodynamically stable patients
      presenting with ACS, LVEDP and coronary perfusion pressure are not predictive of
      in-hospital cardiovascular collapse. SUMMARY: The authors retrospectively
      analyzed 922 patients from a single center who underwent percutaneous coronary
      intervention (PCI) for acute coronary syndromes to evaluate the role of coronary
      perfusion pressure and other left ventricular hemodynamics to predict
      cardiovascular collapse following PCI. They found that neither coronary perfusion
      pressure nor left ventricular end diastolic pressure was predictive of in
      hospital cardiovascular collapse.

PMID- 30217627
TI  - Rotational atherectomy combined with drug coated balloons for in-stent
      restenosis.
AB  - BACKGROUND: Refractory coronary in-stent restenosis remains a clinically relevant
      problem in interventional cardiology despite the use of drug coated balloon
      angioplasty and further drug eluting stent deployment. In this study, we
      investigated whether the novel approach of lesion debulking with rotational
      atherectomy prior to drug coated balloon angioplasty for challenging coronary in
      stent restenosis is safe and effective. METHODS: Procedural and registry data was
      retrospectively analysed for 26 patients who underwent rotational atherectomy
      immediately followed by drug coated balloon angioplasty to 43 coronary in-stent
      restenosis lesions with mean follow up of 19 months. RESULTS: Lesion success was
      achieved in all cases with no major procedural complications. There were no
      instances of death or myocardial infarction in the follow up period. Target
      lesion revascularisation occurred in six patients and target vessel
      revascularisation occurred in eight patients. All target lesion revascularisation
      occurred in lesions that had already failed drug coated balloon angioplasty
      without debulking previously while four such lesions were free of lesion failure
      in the follow up period. CONCLUSIONS: Lesion debulking with rotational
      atherectomy followed by drug coated balloon angioplasty is a feasible treatment
      option for selected cases of in-stent restenosis. Further study is needed to
      fully assess its efficacy in comparison to conventional treatment.

PMID- 30217628
TI  - Uncharted Waters: Challenges in the Era of Biologic Therapies for Nasal
      Polyposis.
AB  - Several new, promising, targeted therapies for nasal polyposis are being tested
      in large-scale clinical trials. These agents target pathways thought to be
      involved in the disease, including IgE, IL-5, IL-4/IL-13, and others. Designing
      these trials poses significant challenges: who and when to enroll is not
      completely clear, optimal dosing is not known, outcome measures are
      insufficiently robust, there are no validated biomarkers, trial regimens may not
      comport with how clinicians might use these drugs once approved, and cost-benefit
      ratios have not been assessed. Thus, there is a need to consider such questions,
      as trials of these novel treatments continue and these biologics become
      available. Despite these uncertainties about trial design, there remains a great
      deal of excitement in the field as we approach the dawn of a new era of
      therapeutic options for nasal polyposis. In this rostrum, we enumerate these
      issues and call for a conference that will allow stakeholders in the field to
      confront them as we enter this new era of opportunity to advance the treatment of
      nasal polyposis.

PMID- 30217629
TI  - Surgical versus medical treatment for ocular surface squamous neoplasia: A
      quality of life comparison.
AB  - PURPOSE: To characterize vision-related and psychosocial quality of life (QoL)
      parameters in medically and surgically treated patients with OSSN. METHODS: Forty
      one patients with OSSN treated with medical therapy consisting of interferon
      alpha 2b drops 1 MIU/ml (n = 22) or who underwent surgical excision (n = 19) were
      contacted. All subjects answered a quality of life assessment with an original
      questionnaire in which they were asked about a range of parameters. Overall
      satisfaction and motivating factors for treatment were also reviewed. RESULTS:
      The mean age at the time of the survey was 64.6 and 51% were male with similar
      demographics between groups. Based on the previous cohort, rates of tumor
      resolution and recurrences were comparable in the two groups. Reasons for
      choosing a particular treatment varied between the groups. Forty percent of
      individuals in the medical group reported a fear of surgery (p = 0.03) and often
      made the decision after personal research (p = 0.008). Thirty-two percent of
      patients in the surgical group chose surgery due to fear of decreased vision due
      to lesion growth, therefore wanting immediate resolution (p = 0.09). Drops
      precipitated more ocular symptoms such as tearing and itchiness, on the other
      hand, patients who had surgery reported having more pain. CONCLUSION: Quality of
      life considerations before, during, and after OSSN treatment is an important yet
      understudied topic. Our study is the first to look at QoL parameters in OSSN
      treatment and we found that patients in both medically and surgically treated
      groups had similar QoL metric but were driven to choose chemotherapy due to fear
      of surgery and/or prior literature review.

PMID- 30217630
TI  - The U Shape of Prostate-specific Antigen and Prostate Cancer-specific Mortality
      in High-grade Metastatic Prostate Adenocarcinoma.
AB  - BACKGROUND: Accumulated evidence suggests that metastatic prostate cancer (mPCa)
      with a low prostate-specific antigen (PSA) level may be a unique entity. However,
      its clinical features and prognosis have not been fully evaluated. OBJECTIVE: To
      investigate the clinical features of low-PSA mPCa and the impact of low PSA level
      on overall survival (OS) and PCa-specific mortality (PCSM) of mPCa. DESIGN,
      SETTING, AND PARTICIPANTS: A total of 8479 mPCa patients were retrieved from the
      Surveillance, Epidemiology, and End Results program (2010-2015). The median
      follow-up was 18 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox
      regression and Fine-Gray competing risk were used to calculate the hazard ratio
      (HR) and subdistribution hazard ratio (sHR) for OS and PCSM, respectively.
      RESULTS AND LIMITATIONS: A higher rate of T4 stage disease (19.8%) and visceral
      metastasis (18.2%) and the shortest median OS (34 mo) were observed in mPCa
      patients with Gleason 8-10 and PSA <=4ng/ml. In the Cox regression model, PSA
      <=4ng/ml was a significant predictor of OS for Gleason 8-10 disease. The
      distribution of PCSM by PSA was U-shaped for Gleason score 8-10 (PSA 4.1-10ng/ml
      as the referent), with an adjusted sHR of 1.52 for PSA <=4.0ng/ml (95% confidence
      interval: 1.17-1.96) versus 0.99 for PSA 10.1-20ng/ml and 1.35 for PSA >20ng/ml.
      In contrast, the distribution of PCSM by PSA was linear for Gleason 5-7.
      Sensitivity analyses showed similar results in Gleason 9-10 and Gleason 10
      subgroup. The study is limited by its retrospective design. CONCLUSIONS: Low PSA,
      high-grade mPCa has a higher proportion of T4 stage disease, visceral metastasis,
      and PCSM. PATIENT SUMMARY: We found that 2.8% of high-grade metastatic prostate
      cancer has a prostate-specific antigen level <=4ng/ml at diagnosis. This
      population has aggressive clinical features and a poor cancer-specific outcome.
      Our results highlighted this under-reported population, and the management of
      these patients warrants further research.

PMID- 30217631
TI  - The Importance of Technical and Non-technical Skills in Robotic Surgery Training.
AB  - We discuss the differences in cognitive (thinking) and other non-technical skills
      (NTS) in robotic surgery training compared to other approaches to surgery.
      Recognition of the importance of NTS and cognitive training will aid the
      development of robotic surgery curricula.

PMID- 30217632
TI  - Seeing is believing: Quality assurance with endovascular scopes.

PMID- 30217633
TI  - Stent use in patients with Marfan syndrome: Not so crazy after all.

PMID- 30217634
TI  - Acute aortic dissections with entry tear in the aortic arch: International
      Registry of Acute Aortic Dissection to the rescue.

PMID- 30217635
TI  - Is this really a step forward?

PMID- 30217636
TI  - Analysis of Risk Factors Increased Hemorrhagic Transformation after Acute
      Ischemic Stroke.
AB  - BACKGROUND: The purpose of this study was to analyze the risk factors of
      hemorrhagic transformation (HT) after intravenous thrombolysis using a
      recombinant tissue plasminogen activator (r-tPA) in acute ischemic stroke (AIS).
      METHODS: We included 199 consecutive patients in the First Affiliated Hospital of
      Wenzhou Medical University from January 2016 to October 2017 with a diagnosis of
      AIS. The patients were divided into 2 groups: HT and non-HT. The related risk
      factors were recruited before and after receiving r-tPA thrombolysis. RESULTS:
      Using univariate analysis, we found that there was a significant difference
      between the HT and non-HT group (P < .05) in the level of age, atrial
      fibrillation, baseline National Institute of Health Stroke Scale (NIHSS) score
      and NIHSS score after 2 hours of thrombolytic therapy, hyperlipidemia.
      Multivariate logistic regression analysis indicated that NIHSS score after 2
      hours of thrombolytic therapy (odds ratio [OR] = 1.091, 95% confidence interval
      [CI] = 1.015-1.173 P = .018) and atrial fibrillation (OR = 2.188, 95%CI  = 1.024
      4.672 P = .043) are the risk factors of HT. CONCLUSIONS: NIHSS score after 2
      hours of thrombolytic therapy and atrial fibrillation were risk factors for HT
      after thrombolysis. Age (OR = 1.022, 95%CI = .988-1.056 P = .205), Hyperlipidemia
      (OR = .591, 95%CI = .29-1.206 P = .148), and Baseline NIHSS score (OR = .998,
      95%CI = .914-1.089 P = .043) were not significant independent predictors but
      showed an association with HT. These 5 factors should be carefully taken into
      account.

PMID- 30217637
TI  - Immune-Thrombotic Thrombocytopenic Purpura is a Rare Cause of Ischemic Stroke in
      Young Adults: Case Reports and Literature Review.
AB  - INTRODUCTION: Immune thrombotic thrombocytopenic purpura (i-TTP), related to
      acquired ADAMTS-13 dysfunction, can lead to various neurological symptoms
      including ischemic stroke. To date the clinical, radiological, and biological
      characteristics of patients having a stroke as the inaugural manifestation of i
      TTP are largely unknown. METHODS: Probable immune-TTP was defined by a low ADAMTS
      13 activity associated with the presence of ADAMTS-13 inhibitors and/or favorable
      clinicobiological response under immunological treatments. The clinical,
      radiological, biological data and outcome under treatment are described in a
      cohort of 17 patients coming from 3 local cases and a literature review. RESULTS:
      Fourteen of the 17 patients were female and the mean age was 41 years. None of
      the patients had the classical pentad of TTP. Only 41% had a combination of
      thrombocythemia and hemolysis. Stroke was multifocal in 35% and included large
      artery strokes. No adverse event was observed following intravenous thrombolysis.
      Refractory and relapsing forms were observed in 47%. DISCUSSION: The clinical,
      radiological, and biological presentation of patients with stroke as the
      inaugural presentation of i-TTP is heterogeneous. This diagnosis should be
      discussed in every young adult with ischemic stroke of undetermined source.

PMID- 30217638
TI  - The Effects of Lipopolysaccharide on the Disrupted Blood-Brain Barrier in a Rat
      Model of Preeclampsia.
AB  - BACKGROUND: Preeclampsia is a disorder characterized by high blood pressure and
      often proteinuria during pregnancy. It is known that a subseptic dose of
      bacterial lipopolysaccharide (LPS) induces production of proinflammatory
      cytokines, and possibly increasing the risk for developing preeclampsia. We
      investigated the effects of LPS on the blood-brain barrier (BBB) integrity in
      pregnant rats with N(omega)-nitro-l-arginine methyl ester (L-NAME) induced
      preeclampsia. METHODS: Starting from the 10th day of gestation, pregnant rats
      were given L-NAME for 10 days to produce hypertension and proteinuria. Animals
      were then treated with a single injection of LPS on the 19th day of pregnancy.
      Arterial blood pressure and proteinuria were measured on the day of the
      experiment, which was 24 hours after the LPS injection. The BBB integrity was
      assessed by using Evans blue (EB) and horseradish peroxidase (HRP) tracers.
      RESULTS: Proteinuria was observed in varying degrees, and the arterial blood
      pressure increased in L-NAME-treated pregnant rats (P < .01). The overall brain
      EB content did not increase in these preeclamptic rats when compared to pregnant
      animals, and LPS treatment also did not change EB content. Ultrastructurally,
      frequent vesicles containing HRP reaction products were observed in the capillary
      endothelial cells in the cerebral cortex and hippocampus of pregnant rats treated
      with L-NAME (P < .01). However, LPS did not change the amounts of HRP that mainly
      accumulated in brain capillary endothelial cells of these animals. CONCLUSION:
      Our results suggest that, in this experimental setting, LPS does not change the
      severity of BBB disruption observed in preeclamptic animals.

PMID- 30217639
TI  - KRAS-specific Amino Acid Substitutions are Associated With Different Responses to
      Chemotherapy in Advanced Non-small-cell Lung Cancer.
AB  - BACKGROUND: Emerging data highlight different clinical behaviors according to
      KRAS amino acid substitutions (AASs) in patients with non-small-cell lung cancer
      (NSCLC). We aimed to evaluate whether different KRAS AASs were associated with
      different responses to chemotherapy. PATIENTS AND METHODS: We retrospectively
      reviewed data from 1190 patients with KRAS mutations who underwent first-line
      platinum-based chemotherapy for stage IV NSCLC. The response to different
      chemotherapy regimens was evaluated using the Response Evaluation Criteria In
      Solid Tumors criteria (v 1.1). Overall survival and time to progression (TTP)
      were secondary endpoints. RESULTS: Taxane was associated with the best response
      in the entire cohort (odds ratio, 2.52; 95% confidence interval [CI], 1.82-3.48;
      P < .001), especially in G12V patients (odds ratio, 2.15; 95% CI, 1.05-4.41; P =
      .036). Taxane was associated with improved TTP in the entire cohort (hazard ratio
      [HR], 0.31; 95% CI, 0.26-0.38; P < .001), especially in G13D patients (HR, 0.47;
      95% CI, 0.22-1.01; P = .054). Pemetrexed was associated with the worst TTP in the
      entire cohort, particularly in G12V patients, who had the worst response rates
      (HR, 0.55; 95% CI, 0.30-0.99; P = .049). No impact on overall survival was
      observed according to different chemotherapy regimens and AASs. CONCLUSION: KRAS
      specific AAS appears to induce different responses to chemotherapy regimens after
      first-line platinum-based chemotherapy in advanced NSCLC.

PMID- 30217640
TI  - Impact of Vasoactive Medications on ICU-Acquired Weakness in Mechanically
      Ventilated Patients.
AB  - BACKGROUND: Vasoactive medications are commonly used in the treatment of
      critically ill patients, but their impact on the development of ICU-acquired
      weakness is not well described. The objective of this study is to evaluate the
      relationship between vasoactive medication use and the outcome of ICU-acquired
      weakness. METHODS: This is a secondary analysis of mechanically ventilated
      patients (N = 172) enrolled in a randomized clinical trial of early occupational
      and physical therapy vs conventional therapy, which evaluated the end point of
      ICU-acquired weakness on hospital discharge. Patients underwent bedside muscle
      strength testing by a therapist blinded to study allocation to evaluate for ICU
      acquired weakness. The effects of vasoactive medication use on the incidence of
      ICU-acquired weakness in this population were assessed. RESULTS: On logistic
      regression analysis, the use of vasoactive medications increased the odds of
      developing ICU-acquired weakness (odds ratio [OR], 3.2; P = .01) independent of
      all other established risk factors for weakness. Duration of vasoactive
      medication use (in days) (OR, 1.35; P = .004) and cumulative norepinephrine dose
      (MUg/kg/d) (OR, 1.01; P = .02) (but not vasopressin or phenylephrine) were also
      independently associated with the outcome of ICU-acquired weakness. CONCLUSIONS:
      In mechanically ventilated patients enrolled in a randomized clinical trial of
      early mobilization, the use of vasoactive medications was independently
      associated with the development of ICU-acquired weakness. Prospective trials to
      further evaluate this relationship are merited. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01777035; URL: www.clinicaltrials.gov.

PMID- 30217641
TI  - North American naturopathic medicine in the 21st century: Time for a seventh
      guiding principle - Scientia Critica.
AB  - The World Health Organization strategy for global health includes a culturally
      sensitive blending of western biomedicine with traditional forms of healing; in
      practical terms this approach is often referred to as integrative medicine. One
      distinct element within the systems of North American integrative healthcare is
      naturopathic medicine; while the basic premise of its fundamental approach to
      care - supporting healthy lifestyle behaviors - is as old as medicine itself, the
      early history of organized naturopathy in North America was heavy in theory and
      light on critical analysis. Dozens of questionable modalities and protocols have
      been housed under the rubric of naturopathy. It is our contention that the
      progression of professional naturopathic medicine in the 21st century - with
      goals of personal, public and planetary health - requires the active pursuit of
      critical analysis. We examine the primary guiding principles which drive the
      training and practice of North American naturopathic medicine; while these
      principles are laudable in the age of patient-centered care, we argue that there
      are shortcomings by absentia. We propose a seventh principle - Scientia Critica;
      that is, the ability to critically analyze accumulated knowledge - including
      scientific facts, knowledge about the self (critical consciousness) and values of
      the patient.

PMID- 30217642
TI  - Severe Leg Pain Following Spinal Cord Stimulator Implantation - A Case Report.
AB  - Following spinal cord stimulator (SCS) implantation, post-operative pain is
      commonly incisional or neuropathic from neurological damage. Occasionally, this
      new pain may mimic symptoms due to pre-existing pathology. We present a case of
      immediate, severe, post-operative leg pain secondary to a lower extremity deep
      vein thrombosis (DVT) and subsequent pulmonary embolism (PE) after percutaneous
      SCS implantation for failed back syndrome. The risk factors of DVT after spine
      surgery and perioperative prophylaxis will be further discussed with a brief
      literature review.

PMID- 30217643
TI  - Ultrasonographic Evaluation of the Femoral Cartilage, Achilles Tendon and Plantar
      Fascia in Young Women Wearing High-heeled Shoes.
AB  - BACKGROUND: Specific attention on the musculoskeletal impact of wearing high
      heeled shoes (HHS) has mainly focused on knee osteoarthritis and the literature
      is limited to biomechanical changes. Herewith, the distal femoral cartilage (DFC)
      has not been morphologically studied. Additionally, although heel elevation is
      coupled with a shear stress at the heel and overloaded calf muscles, Achilles
      tendon and plantar fascia thicknesses have not been assessed either. OBJECTIVE:
      To investigate whether the DFC, Achilles tendon (AT), and plantar fascia (PF)
      were different in women wearing HHS and flat-heeled shoes (FHS) and specifically,
      different in terms of AT/PF and DFC thicknesses. DESIGN: Cross-sectional
      observational study. SETTING: Tertiary care center. PARTICIPANTS: There were 34
      women (mean age; 31.1+/-6.4, body mass index (BMI); 21.6+/-2.4 kg/m2) in the HHS
      group and 54 women (mean age; 29.5+/-7.2 years, BMI 22.5+/-2.9 kg/m2) in the FHS
      group (P=.271, P=.102, respectively). Women wearing shoes with a heel height of >
      5 cm were enrolled in the HHS group, and those wearing shoes with a heel height
      of < 1.4 cm were included in the FHS group. MAIN OUTCOME MEASUREMENTS: Distal
      femoral cartilage from the lateral condyle, intercondylar area and medial condyle
      (MFC), Achilles tendon and plantar fascia thicknesses, and any abnormalities were
      evaluated bilaterally by ultrasound. RESULTS: Within-group comparisons yielded
      thicker right MFC (P=.022) and left AT (P=.028) only in the HHS group. Between
      group comparisons yielded thicker left AT in the HHS group (P=.040). PF
      thicknesses were similar both within and between group comparisons (all P > .05).
      Right AT thickness was positively correlated with right (r=0.469, P=.005) and
      left (r=0.402, P=.018) PF thicknesses only within the HHS group. Only calcaneal
      irregularity/spur was found to be common in the HHS group (P=.038). CONCLUSIONS:
      We found thickening of the right MFC and left AT in those wearing HHS, whereas PF
      thickness was not significantly different.

PMID- 30217644
TI  - Popliteal Artery Entrapment Syndrome - Return to Sport Considerations: A Case
      Report.
AB  - This is a case of a 19-year-old female collegiate field hockey player with left
      leg pain, numbness and tingling. A comprehensive workup including dynamic
      ultrasound, Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiogram
      (MRA) revealed a type VI functional popliteal artery entrapment syndrome (PAES).
      There are many options for treatment of functional PAES including activity
      modification, botulinum toxin injection, and surgery. To the authors knowledge
      there is no published return to sport recommendation for post-surgical functional
      PAES . The aim of this study is to highlight alternative treatment options and
      propose a post-surgical return to play rehabilitation protocol in functional
      PAES.

PMID- 30217645
TI  - Performance evaluation of poly (l-lactide-co-D, l-lactide)/poly (acrylic acid)
      blends and their nanofibers for tissue engineering applications.
AB  - Poly (l-lactide-co-D, l-lactide) (PLDLLA) is a biodegradable polymer
      predominantly used in biomedical applications. Despite unprecedented
      characteristics of PLDLLA, its wettability, mechanical properties, degradation,
      and cell attachment are main issues to improve. In this work, different blend
      films based on PLDLLA/poly (acrylic acid) (PAAc) are prepared to evaluate their
      miscibility, hydrophilicity, hydrolytic degradation and mechanical properties.
      For this purpose, a series of experiments such as DSC alongside SEM, water
      contact angle (WCA)/water up-take, weight measurements in phosphate buffer saline
      (PBS) and NaOH as well as tensile test are carried out. The DSC and SEM results
      show a miscibility for the blends, and hence by increasing PAAc, the WCA values
      and degradation rates are decreased and increased, respectively. Moreover, the
      degradation mechanisms of the blend samples follow surface/bulk erosion and bulk
      process in the alkaline and PBS environments, respectively. Subsequently, PLDLLA
      and its blends are electrospun to prepare nanofibrous samples, thereby assessing
      their cytotoxicity and cell viability by the use of thiazolyl blue assay and
      acridine orange/ethidium bromide staining, respectively. The in vitro SNL 76/7
      fibroblast cells cultivation onto the surface of the blend with 10% wt. of PAAc
      revealed that this sample is a promising candidate for tissue engineering
      applications.

PMID- 30217646
TI  - Recent advances in the production strategies of microbial pectinases-A review.
AB  - Pectinases, member of the hydrolases family of enzymes, are one of the important
      enzymes of the biotechnological sector with 25% share in the global food and
      beverage enzyme market. They hold a leading position among the commercially
      produced industrial enzymes. These enzymes are sustainable and environmentally
      friendly tool of nature with wide application perspective in many industrial
      processes, such as, retting and degumming of plant fibers, fermentation of tea
      and coffee, oil extraction, clarification of fruit juices and wine, valorization
      of industrial wastes, debasement of cellulosic biomass for biofuel production,
      wastewater remediation, desizing, scouring and bleaching of fabric, animal feed
      production, and protoplast fusion technology etc. However, like many other
      industrial enzymes, pectinases also face the constraint of low yield and
      productivity in its economized production. Therefore, pectinases have been the
      target of studies aiming to achieve the expression levels on a commercial scale.
      Among the natural sources of pectinases, microbial pectinases are employed
      frequently owing to its ease of production and unique physicochemical properties.
      This review mainly focuses on the production of pectinase enzymes along with
      different types of recent strategies used for their production optimization to
      get overexpression/production. The promise of genetic engineering approaches
      applied so far to get the higher production of these enzymes using simpler
      molecular devices and simple fermentation media is also covered in this review.

PMID- 30217647
TI  - Improved in vitro antioxidant and antimicrobial capacities of polysaccharides
      isolated from Salicornia arabica.
AB  - A newly profiling of Salicornia arabica (SAPS) polysaccharides was investigated.
      The water-soluble polysaccharide extract extracted from the Tunisian halophyte
      (SA) contained sulfate (9.64 +/- 0.003%), carbohydrate (86.33 +/- 0.003%),
      protein (1.24%), and uronic acids (3.33 +/- 0.37%). The analysis of the
      monosaccharide composition revealed the presence of arabinose, Glucopyranose
      galactose, Glucuronic acid and glucose. The identified polysaccharide was
      considered as heterogeneous and highly branched via gaz chromatography, Fourier
      Transform Infrared Spectrometer (FT-IR), Thin layer chromatography (TLC)
      analysis. It also displayed an important radical scavenging and reducer power as
      well it exhibited effective antimicrobial properties.

PMID- 30217648
TI  - Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a
      systematic review.
AB  - BACKGROUND: Transcutaneous Vagus Nerve stimulation (tVNS) may be an alternative
      to surgically implanted VNS for epilepsy and other diseases. However, its safety
      and tolerability profile is unclear. OBJECTIVE: We performed a systematic review
      of treatment harms from tVNS in humans. METHODS: A systematic published and grey
      literature search was carried out to identify studies which deployed tVNS in
      human subjects. Study authors were contacted for safety/tolerability data if
      these were not available in the publication. Databases were searched from 1966 to
      May 2017. We noted study type, population, stimulation parameters, type and
      prevalence of side effects and/or serious adverse events (SAE). We also noted
      whether side effects/SAE were considered to be related to the tVNS and the
      proportion of participants dropping out of studies due to side effects. RESULTS:
      51 studies were included comprising a total of 1322 human subjects receiving
      tVNS. The most common side effects were: local skin irritation from electrode
      placement (240 participants, 18.2%), headache (47, 3.6%) and nasopharyngitis (23,
      1.7%). Whilst heterogeneity in overall side effect event rates between studies
      was not accounted for by the frequency (Hz) or pulse width (ms) of stimulation, a
      minority (35 participants (2.6%)) dropped out of studies due to side effects.
      Overall, 30 SAE occurred but only 3 were assessed by the relevant researchers to
      be possibly caused by tVNS. CONCLUSION: tVNS is safe and well tolerated at the
      doses tested in research studies to date.

PMID- 30217649
TI  - Subgenomic flaviviral RNAs: What do we know after the first decade of research.
AB  - The common feature of flaviviral infection is the accumulation of abundant virus
      derived noncoding RNA, named flaviviral subgenomic RNA (sfRNA) in infected cells.
      This RNA represents a product of incomplete degradation of viral genomic RNA by
      the cellular 5'-3' exoribonuclease XRN1 that stalls at the conserved highly
      structured elements in the 3' untranslated region (UTR). This mechanism of sfRNA
      generation was discovered a decade ago and since then sfRNA has been a focus of
      intense research. The ability of flaviviruses to produce sfRNA was shown to be
      evolutionary conserved in all members of Flavivirus genus. Mutations in the 3'UTR
      that affect production of sfRNAs and their interactions with host factors showed
      that sfRNAs are responsible for viral pathogenicity, host adaptation, and
      emergence of new pathogenic strains. RNA structural elements required for XRN1
      stalling have been elucidated and the role of sfRNAs in inhibiting host antiviral
      responses in arthropod and vertebrate hosts has been demonstrated. Some molecular
      mechanisms determining these properties of sfRNA have been recently
      characterized, while other aspects of sfRNA functions remain an open avenue for
      future research. In this review we summarise the current state of knowledge on
      the mechanisms of generation and functional roles of sfRNAs in the life cycle of
      flaviviruses and highlight the gaps in our knowledge to be addressed in the
      future.

PMID- 30217650
TI  - Immunization with a synthetic consensus hepatitis C virus E2 glycoprotein
      ectodomain elicits virus-neutralizing antibodies.
AB  - Global eradication of hepatitis C virus (HCV) infection will require an
      efficacious vaccine capable of eliciting protective immunity against genetically
      diverse HCV strains. Natural spontaneous resolution of HCV infection is
      associated with production of broadly-neutralizing antibodies targeting the HCV
      glycoproteins E1 and E2. As such, production of cross-neutralizing antibodies is
      an important endpoint for experimental vaccine trials. Varying success generating
      cross-neutralizing antibodies has been achieved with immunogens derived from
      naturally-occurring HCV strains. In this study the challenge of minimising the
      genetic diversity between the vaccine strain and circulating HCV isolates was
      addressed. Two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) were
      derived from consensus nucleotide sequences deduced from samples of circulating
      genotype 1 HCV strains. These two synthetic sequences differed in their relative
      positions in the overall genotype 1a/1b phylogeny. Expression of these constructs
      in Drosophila melanogaster S2 cells resulted in high yields of correctly-folded,
      monomeric E2 protein, which were recognised by broadly neutralizing monoclonal
      antibodies. Immunization of guinea pigs with either of these consensus
      immunogens, or a comparable protein representing a circulating genotype 1a strain
      resulted in high titres of cross-reactive anti-E2 antibodies. All immunogens
      generated antibodies capable of neutralizing the H77 strain, but NotC1 elicited
      antibodies that more potently neutralized virus entry. These vaccine-induced
      antibodies neutralized some viruses representing genotype 1, but not strains
      representing genotype 2 or genotype 3. Thus, while this approach to vaccine
      design resulted in correctly folded, immunogenic protein, cross-neutralizing
      epitopes were not preferentially targeted by the host immune response generated
      by this immunogen. Greater immunofocussing of vaccines to common epitopes is
      necessary to successfully elicit broadly neutralizing antibodies.

PMID- 30217651
TI  - A novel antiviral inhibits Zika virus infection while increasing intracellular
      glutathione biosynthesis in distinct cell culture models.
AB  - We investigated the effects of a specific free-form amino acids formulation on
      Zika virus replication in two different cell culture model systems, one
      representative of humans and the other of Old World primates from whom Zika virus
      was first isolated. Here we present data demonstrating that the formulation of
      the specific free-form amino acid (FFAAP), comprising cystine, glycine, and a
      glutamate source, along with a minute concentration of selenium inhibited Zika
      virus replication by up to 90% with an ED90 (effective dose at which 90% of a
      dose of Zika virus was inhibited) of 2.5 mM in human cells and 4 mM Vero cells.
      The ED90 concentration of precursors was innocuous for uninfected cells, but
      resulted in reduced Zika virus replication by up to 90% at 2-5 mM concentrations
      in nonhuman primate cells and at 1-3 mM concentration in human placental cells.
      Two important observations were forthcoming: 1) Zika virus production was
      decreased by up to 90% in Vero and JEG-3 cells treated with FFAAP (ED90 4.0 mM,
      and 2.5 mM, respectively) throughout 48-72 h of post infection (hpi) compared to
      untreated infected cells and 2) Zika virus requires intracellular glutathione for
      replication in human placental cells, while showing enhanced replication in Vero
      cells with no glutathione. Relative increases in intracellular glutathione
      biosynthesis followed FFAAP treatment but blocking intracellular biosynthesis of
      glutathione in human cells resulted in virus inhibition in human placental cells.
      The blockade of biosynthesis actually increased Zika virus replication in Vero
      cells. These findings identify an efficacious inhibitor, FFAAP, of Zika virus
      replication in both human and nonhuman primate cells, while providing novel
      insight into the different roles of intracellular glutathione in Zika virus
      replication.

PMID- 30217652
TI  - Mifepristone potentiates etoposide toxicity in Hep G2 cells by modulating drug
      transport.
AB  - Etoposide is a well-known and widely used anticancer drug that displays several
      side effects. In addition, tumors often acquire resistance to this drug. Our aim
      is to develop a combination therapy that would augment toxicity of etoposide in
      malignant cells. Based on literature and our experiments, we selected
      mifepristone (RU486) as a potential supporting molecule that is able to enhance
      etoposide toxicity against cancer cells. All experiments were performed with Hep
      G2 cells, a well-known and described human hepatocellular carcinoma cell line. By
      using xCELLigence system, we demonstrated that mifepristone enhances toxicity of
      etoposide in a dose dependent manner with concomitant caspase-3 activity. We
      evaluated upregulation of Bax because mifepristone was demonstrated to modulate
      proapoptotic Bax protein expression. Our data show only weak and not
      statistically significant increase of Bax expression. On the other hand, we show
      that mifepristone increases etoposide toxicity via inhibition of ABC
      transporters, coupled with significant increase of intracellular etoposide
      concentration. In conclusion, we demonstrate that mifepristone has a synergistic
      effect with etoposide treatment in the Hep G2 cells and that the effect is
      related to ABC transporters inhibition.

PMID- 30217653
TI  - Proposed mechanism for understanding the dose- and time-dependency of the effects
      of fluoride in the liver.
AB  - Fluoride (F) can induce changes in the expression of several liver proteins. It
      is suggested that these changes are dose- and time-dependent. The objective of
      this study was to analyze the effect of different F concentrations and exposure
      times to this ion on the pattern of protein expression in the liver of rats.
      Thirt-six 21-day-old male Wistar rats were divided into 2 groups (n = 18)
      according to the treatment duration (20 or 60 days). Each of these groups was
      then divided into 3 subgroups (n = 6) according to the concentration of F
      administered in drinking water, as follows: 0 mg/L (control), 15 mg/L or 50 mg/L.
      After the experiment periods, the animals were anesthetized and the liver and
      blood were collected. F was analyzed in plasma and liver. Part of the liver was
      fixed for histological analysis. Liver proteins were extracted and prepared for
      quantitative label-free mass spectrometry analysis. F concentrations in plasma
      and liver were significantly higher in the group treated with 50 mg /L in
      comparison with control, regardless the time of exposure. Histological
      alterations in the liver were more evident in the subgroups treated for 20 days.
      The proteomic analysis revealed changes in proteins related to endoplasmic
      reticulum and mitochondrial oxidative stress, mitochondrial alteration, apoptosis
      and cellular respiration upon exposure to F. The results reinforce previous
      findings showing that the effects of F in the liver are dose- and time-dependent
      and provide the molecular basis for understanding the evolution of these effects.

PMID- 30217654
TI  - Challenging biocide tolerance with antiseptic stewardship.

PMID- 30217655
TI  - Unforeseen challenges of living with an LVAD.
AB  - BACKGROUND: The implantable left ventricular assist device (LVAD) is being used
      more commonly, and is associated with improved outcomes physically but can be
      related to psychological distress. KEY POINTS: A 28-year-old male of Asian
      ethnicity who received LVAD implantation for advanced heart failure. Incidents
      are described wherein the external battery pack for his LVAD was misidentified as
      an explosive device, and he a security threat. These impacted on the patient's
      psychological wellbeing. These difficulties were ameliorated after successful
      heart transplant. CONCLUSIONS: Similar incidents could occur, as rates of hate
      crimes and support for racial profiling increase. Thus, this report calls for
      greater recognition of the challenge of living with the LVAD by clinicians,
      leading to better patient education and increased access to psychological
      therapy. There is also an avenue for national bodies to develop greater awareness
      of LVAD and improve access to psychological support.

PMID- 30217656
TI  - New synthetic opioids: Part of a new addiction landscape.
AB  - Synthetic opioids (SO) are a major risk for public health across the world. These
      drugs can be divided into 2 categories, pharmaceutical and non-pharmaceutical
      fentanyls. A new generation of SO has emerged on the drug market since 2010.
      North America is currently facing an opioid epidemic of morbi-mortality, caused
      by over-prescription of opioids, illegally diverted prescribed medicines, the
      increasing use of heroin and the emergence of SO. Furthermore, this opioid crisis
      is also seen in Europe. SO are new psychoactive substances characterized by
      different feature such as easy availability on the Internet, low price, purity,
      legality, and lack of detection in laboratory tests. They have not been approved
      or are not recommended for human use. Opioid misuse is associated with somatic
      and psychiatric complications. For many substances, limited pharmacological
      information is available, increasing the risk of harmful adverse events. Health
      actors and the general population need to be clearly informed of the potential
      risks and consequences of the diffusion and use of SO.

PMID- 30217657
TI  - Expression profile of the CSF3 and LPO genes in milk from buffalo (Bubalus
      bubalis) with and without mastitis.
AB  - This study compared the expression profile of the candidate genes, CSF3 and LPO,
      by investigating the immune response mechanisms involved in the phenotype of
      resistance and susceptibility to mastitis of healthy and infected buffaloes. The
      Granulocyte Colony Stimulating Factor 3 (CSF3) and Lactoperoxidase (LPO) genes
      expression profiles were determined in 24 milk samples from buffaloes with (N =
      12) and without (N = 12) mastitis, using the quantitative real-time PCR (qRT-PCR)
      technique. CSF3 and LPO expressions were 5.14 (P = 0.001) and 2.41 (P = 0.097)
      times higher in animals with mastitis compared to healthy animals, respectively,
      evidencing a trend toward different expressions of this gene in the studied
      groups. Our finding suggests that LPO and CSF3 genes are an important defense
      mechanism against mastitis in dairy buffaloes, and may be putative genes for
      selecting healthier animals in buffalo breeding programs.

PMID- 30217658
TI  - Molecular diversity of Coxsackievirus A10 circulating in the southern and
      northern region of India [2009-17].
AB  - Non-Polio EnteroViruses (NPEV) are one of the known causative agents of Acute
      Flaccid Paralysis (AFP). In the present study, we identified, sequenced and
      characterized the complete genome of sixty-five Coxsackievirus-A10, an NPEV.
      These were isolated from stool specimens of AFP cases from Bihar, Karnataka,
      Kerala, and Uttar Pradesh (UP) states of India. Evolutionary analysis of complete
      genome (7420 nucleotides) and VP1 gene (894 nucleotides) demonstrates that there
      are four different intra-typic strains circulating in India which were dissimilar
      to Chinese strains. First intratypic strain circulating in UP, Bihar, and
      Karnataka; second in UP and Karnataka; third in UP and Bihar and; fourth was
      restricted only to Kerala state. The divergence of Kerala strain with respect to
      all other circulating strain of UP, Bihar and Karnataka states in India is 24%,
      24.9%, and 24.4% respectively. Recombinations were observed between few of these
      strains which might be one of the factors of the observed intra-typic diversity.
      ARTICLE SUMMARY LINE: We report the identification, characterization and
      phylogenetic analysis of sixty-five Non-Polio Enterovirus (NPEV) isolates,
      performed during the year 2009-17, causing acute flaccid paralysis in pediatric
      cases with their divergences and recombinations from four states of India.

PMID- 30217659
TI  - Improving the microbiological diagnosis of tuberculous meningitis: A prospective,
      international, multicentre comparison of conventional and modified Ziehl-Neelsen
      stain, GeneXpert, and culture of cerebrospinal fluid.
AB  - OBJECTIVES: Tuberculous meningitis (TBM) is the severest form of tuberculosis,
      but current diagnostic tests are insensitive. Recent reports suggest simple
      modifications to conventional cerebrospinal fluid (CSF) Ziehl-Neelsen (ZN)
      staining may greatly improve sensitivity. We sought to define the performance of
      modified and conventional ZN stain for TBM diagnosis. METHODS: In hospitals in
      Vietnam, South Africa and Indonesia we conducted a prospective study of modified
      ZN with or without cytospin, conventional ZN smear, GeneXpert, and culture on CSF
      in adults with suspected TBM. RESULTS: A total of 618 individuals were enrolled
      across 3 sites. Compared with the TBM clinical diagnostic gold standard for
      research (definite probable or possible TBM), sensitivity of conventional ZN and
      modified ZN with cytospin were 33.9% and 34.5% respectively (p = 1.0 for the
      difference between tests), compared with culture 31.8% and Xpert 25.1%. Using
      culture as a reference, sensitivities of conventional ZN, modified ZN with
      cytospin, and Xpert were 66.4%, 67.5%, and 72.3%, respectively. Higher CSF volume
      and lactate, and lower CSF:blood glucose ratio were independently associated with
      microbiologically confirmed TBM. CONCLUSIONS: Modified ZN stain does not improve
      diagnosis of TBM. Currently available tests are insensitive, but testing large
      CSF volumes improves performance. New diagnostic tests for TBM are urgently
      required.

PMID- 30217660
TI  - Posterior reversible encephalopathy syndrome in immunoglobulin A-associated
      vasculitis.

PMID- 30217661
TI  - Hallux valgus and metatarsus adductus measurements: inter-reader reliability and
      correlations on radiographs and MRI.
AB  - AIM: To assess inter-reader reliability of metatarsus adductus (MA) using the
      traditional method and Engel's angle (EA) on radiography and magnetic resonance
      imaging (MRI) and assess correlations with hallux valgus (HV). METHODS AND
      MATERIALS: Ninety consecutive patients with radiographs and MRI of the foot were
      included. Two readers measured HV angle (HVA), traditional metatarsus adductus
      angle (MAA), and EA on radiographs and HVA and EA on MRI. Three- and two-way
      mixed model analyses were used for reader agreements. Ninety-five percent
      bootstrap confidence intervals were calculated. The linear mixed model was used
      for association between HVA and EA/MAA. RESULTS: Mean age and male to female
      ratio was 54.2+/-15.4 and 0.4:1, respectively. Mean HVA and EA were 20.6+/-9.4
      and 21.2+/-8, 21.2+/-8.3 and 22.4+/-7.5 on radiographs and MRI, respectively.
      Mean MAA was 18.5+/-5.7 on radiographs. Inter-reader agreement was good for EA
      (ICC=0.73, 0.6) and moderate for MAA (ICC=0.41). Positive correlations between
      HVA, MAA, and EA on radiographs and MRI were found, but none were statistically
      significant (p=0.44 and 0.87). CONCLUSION: Engel's angle is more reproducible.
      Although positive correlations exist between the degrees of HV and MA, they are
      not statistically significant.

PMID- 30217662
TI  - Age modifies the association between apathy and recurrent falling in Dutch
      ambulant older persons with a high fall risk: Recurrent falling in Dutch
      outpatients, does apathy play a role?
AB  - Apathy, a common and disabling behavioural syndrome in older persons, has been
      associated with impaired physical performance and executive dysfunction. Both are
      fall risk factors and they share pathophysiological pathway. We cross-sectionally
      examined the association between apathy and recurrent falling (>=2 falls in the
      past 12 months) and number of falls in the past 12 months in 243 outpatients aged
      >=65 years with >=3 fall risk-factors visiting a fall-clinic after a fall. We
      calculated Odds Ratio's (ORs), Incidence Rate Ratio's (IRRs) and their 95%
      Confidential Intervals (CI95) using multivariable regression and negative
      binomial regression analyses. We adjusted for cognitive functioning, depression,
      the use of fall risk increasing drugs, visual impairment, urine incontinence,
      comorbidity, smoking, use of alcohol, body mass index (BMI), and the number of
      months between assessment of fall risk and of apathy. We assessed effect
      modification by age and gender. In our study, apathy was independently associated
      with recurrent falling in patients aged 65-75 years: OR 2.8 (CI95 1.0-7.7).
      Overall, patients with apathy experienced 1.46 times as many falls in the past 12
      months compared to patients without apathy (IRR 1.46 (CI95 1.0-2.1). To conclude,
      in high fall-risk older outpatients, apathy was cross-sectionally associated with
      recurrent falling in patients aged 65-75 years and the number of falls. Apathy
      appeared to be especially relevant in relation to falling in this age group.
      Whether apathy predicts recurrent falling is yet to be determined.

PMID- 30217663
TI  - Associations of physical activity and depression: Results from the Irish
      Longitudinal Study on Ageing.
AB  - Physical activity (PA) can protect against depression, but few studies have
      assessed whether meeting PA guidelines is sufficient, or if benefits can be
      derived from greater volumes of PA. The present study examines cross-sectional
      and prospective associations between different volumes of moderate-to-vigorous PA
      (MVPA) and walking, and depressive symptoms and status. Participants (n = 4556;
      56.7% female) aged >= 50 years completed the International PA Questionnaire
      (IPAQ) at baseline and the Center for Epidemiological Studies Depression Scale at
      baseline and two years later. Prevalence and incidence of depression were 9.0% (n
      = 410) and 5.0% (n = 207), respectively. After full adjustment, odds of prevalent
      depression were: 40% (OR = 0.60, 95%CI: 0.48-0.76) lower among those meeting PA
      guidelines; 23% (OR = 0.77, 0.49-1.21) and 43% (OR = 0.57, 0.45-0.73) lower among
      those in moderate and high categories, respectively; and, 22% (OR = 0.78, 0.61
      1.01) and 44.0% (OR = 0.56, 0.42-0.74) lower among those in moderate and high
      walking tertiles, respectively. Odds of incident depression were: 23% (OR = 0.77,
      0.58-1.04) lower among those meeting PA guidelines; 37% (OR = 0.63, 0.32-1.22)
      and 20.0% (OR = 0.80, 0.59-1.09) lower among those in moderate and high
      categories, respectively; and, 21% (OR = 0.79, 0.56-1.12) and 25% (OR = 0.75,
      0.52-1.07) lower among those in moderate and high walking tertiles, respectively.
      Moderate and high volumes of MVPA were significantly associated with lower odds
      of concurrent depression, and significantly and non-significantly associated with
      reduced odds of incident depression, respectively. Meeting recommended levels of
      MVPA and walking were associated with significantly lower odds of concurrent
      depression, and non-significantly reduced odds of the development of depression
      over two years.

PMID- 30217664
TI  - An ethically-justifiable, practical approach to decision-making surrounding
      conjoined-twin separation.
AB  - Conjoined twins present unique ethical and palliative care challenges. We present
      an ethically-justifiable, practical approach to decision-making with regards to
      surgical separation. These decisions must account for the short- and long-term
      prognoses for each infant prior to, and after, separation. Other considerations
      include the benefits and burdens of separation and the family's values and goals.
      Caregivers should recognize that decisions surrounding separation may be unduly
      influenced by social biases. The palliative care team aids in developing goals of
      care to guide decision-making by promoting communication between the medical team
      and family. They play an important role in supporting families regardless of the
      planned course of treatment. This support may be social or spiritual in nature,
      and is promoted by the interdisciplinary structure of the team. Early involvement
      of palliative care services facilitates complex decision making and can aid in
      the transition from cure-oriented therapies to support if needed during and after
      the dying process.

PMID- 30217665
TI  - Fatal penetrating neck injury due to defective airbag inflator.
AB  - We present a case of a fatal motor vehicle collision of a 22-year-old car driver,
      who died at the scene after losing control of his car, and subsequently collided
      with a tree by the roadside. The subsequent autopsy revealed penetrating injuries
      on the neck, severing the larynx, carotid artery, jugular vein and fracturing the
      cervical vertebrae. Internal examination showed the offending material to be a
      semi-cylindrical metal fragment, which had lodged within the paravertebral
      muscle. Examination of the car with the authorities found that the metal fragment
      originated from a defective airbag booster cannister, which shattered upon
      deployment.

PMID- 30217666
TI  - Behavioral profiles in Rett syndrome: Data from the natural history study.
AB  - INTRODUCTION: Rett syndrome (RTT) is a complex neurodevelopmental disorder with
      known behavioral abnormalities, both internalizing (e.g., anxiety, social
      withdrawal) and externalizing (e.g., aggression, self-abuse). However, a broad
      evaluation of behavioral abnormalities in a large cohort is lacking. OBJECTIVE:
      In this report, we describe profiles of internalizing and externalizing behaviors
      in individuals evaluated in the multi-center U.S. Rett Natural History Study.
      METHODS: Cross-sectional and longitudinal data were collected from 861 females
      with RTT and from 48 females who have MECP2 mutations without meeting criteria
      for RTT. Standard statistical methods including linear regression evaluated
      internalizing behavioral components from the Child Health Questionnaire (CHQ
      PF50) and externalizing components from the Motor Behavioral Assessment (MBA).
      RESULTS: We found mildly to moderately severe internalizing behaviors in nearly
      all individuals with RTT, while externalizing behaviors were mild and uncommon.
      Internalizing behavior in RTT was comparable to groups with psychiatric
      disorders. Participants with mixed (internalizing and externalizing) behaviors
      were younger and less affected overall, but showed prominent self-injury and
      worsening internalizing behaviors over time. CONCLUSIONS: This study revealed
      that internalizing behaviors are common at a clinically significant level in RTT.
      Understanding clinical features associated with behavioral profiles could guide
      treatment strategies.

PMID- 30217667
TI  - Methylene blue-mediated antimicrobial photodynamic therapy: A novel strategy for
      digital dermatitis-associated sole ulcer in a cow - A case report.

PMID- 30217668
TI  - The possible role of insulin-like growth factor-1 in osteosarcoma.
AB  - Osteosarcoma (OS) is a common malignant tumor of bone, of which clear
      understanding of molecular pathologic process is not yet possible. Insulin-like
      growth factor-1 (IGF-1) is a hormone that plays vital role in development and
      function of many tissues. Unfortunately, IGF-1 and its receptor (IGF-1R)'s over
      expression have been implicated in carcinogenesis, and indicated to constitute a
      risk factor for the development of multiple human cancers, including OS.
      Increased levels of IGF-1 and IGF-1R have been reported in OS, leading to cancer
      progression through transformation, proliferation, pro-metastasis, and decreased
      susceptibility to apoptosis. Over-expression of IGF-1/IGF-1R signaling also
      contributes to tumor cell survival, metastasis, and resistance to
      chemotherapeutic drugs. IGF-1 has been included as an OS marker recently, and
      targeting IGF-1 is an interesting and promising approach in OS therapeutics.
      However more investigations with clinical trials are necessary to validate the
      use of drugs against IGF-1 that may provide a basis for new therapeutic
      approaches to treat this devastating disease. This review article focused on the
      role of IGF-1/IGF-1R in OS progression and therapeutic aspects of OS targeting
      IGF-1.

PMID- 30217669
TI  - Elective Surgical Cancellations in a Tertiary Hospital in the Middle East:
      Quality Improvement Process.
AB  - PURPOSE: Cancellation of elective surgery negatively affects patient outcomes and
      the efficiency of the work environment. The purpose of this project was to
      analyze the cancellation of elective surgeries and identify the best evidence
      based interventions to address cancellations in a tertiary hospital in the Middle
      East. DESIGN: A quality improvement study design. METHODS: A retrospective review
      of cancellations conducted over two 3-month periods in 2016 and 2017. FINDINGS:
      In both phases of the audit, patient-related reasons were the leading cause of
      cancellations. Conducting a preoperative call 2 days before surgery and doing a
      weekly review of the surgery schedule reduced cancellations from 3.8% to 3.5%.
      Cancellations because of patient-related reasons reduced from 81% to 79.7%
      whereas cancellations because of hospital-related reasons reduced from 17.5% to
      15.9%. CONCLUSIONS: Cancellation of surgeries is a worldwide health care issue
      and without understanding the causes of cancellations, it is difficult to devise
      an effective intervention to address this issue.

PMID- 30217670
TI  - A comparison of word embeddings for the biomedical natural language processing.
AB  - BACKGROUND: Word embeddings have been prevalently used in biomedical Natural
      Language Processing (NLP) applications due to the ability of the vector
      representations being able to capture useful semantic properties and linguistic
      relationships between words. Different textual resources (e.g., Wikipedia and
      biomedical literature corpus) have been utilized in biomedical NLP to train word
      embeddings and these word embeddings have been commonly leveraged as feature
      input to downstream machine learning models. However, there has been little work
      on evaluating the word embeddings trained from different textual resources.
      METHODS: In this study, we empirically evaluated word embeddings trained from
      four different corpora, namely clinical notes, biomedical publications,
      Wikipedia, and news. For the former two resources, we trained word embeddings
      using unstructured electronic health record (EHR) data available at Mayo Clinic
      and articles (MedLit) from PubMed Central, respectively. For the latter two
      resources, we used publicly available pre-trained word embeddings, GloVe and
      Google News. The evaluation was done qualitatively and quantitatively. For the
      qualitative evaluation, we randomly selected medical terms from three categories
      (i.e., disorder, symptom, and drug), and manually inspected the five most similar
      words computed by embeddings for each term. We also analyzed the word embeddings
      through a 2-dimensional visualization plot of 377 medical terms. For the
      quantitative evaluation, we conducted both intrinsic and extrinsic evaluation.
      For the intrinsic evaluation, we evaluated the word embeddings' ability to
      capture medical semantics by measruing the semantic similarity between medical
      terms using four published datasets: Pedersen's dataset, Hliaoutakis's dataset,
      MayoSRS, and UMNSRS. For the extrinsic evaluation, we applied word embeddings to
      multiple downstream biomedical NLP applications, including clinical information
      extraction (IE), biomedical information retrieval (IR), and relation extraction
      (RE), with data from shared tasks. RESULTS: The qualitative evaluation shows that
      the word embeddings trained from EHR and MedLit can find more similar medical
      terms than those trained from GloVe and Google News. The intrinsic quantitative
      evaluation verifies that the semantic similarity captured by the word embeddings
      trained from EHR is closer to human experts' judgments on all four tested
      datasets. The extrinsic quantitative evaluation shows that the word embeddings
      trained on EHR achieved the best F1 score of 0.900 for the clinical IE task; no
      word embeddings improved the performance for the biomedical IR task; and the word
      embeddings trained on Google News had the best overall F1 score of 0.790 for the
      RE task. CONCLUSION: Based on the evaluation results, we can draw the following
      conclusions. First, the word embeddings trained from EHR and MedLit can capture
      the semantics of medical terms better, and find semantically relevant medical
      terms closer to human experts' judgments than those trained from GloVe and Google
      News. Second, there does not exist a consistent global ranking of word embeddings
      for all downstream biomedical NLP applications. However, adding word embeddings
      as extra features will improve results on most downstream tasks. Finally, the
      word embeddings trained from the biomedical domain corpora do not necessarily
      have better performance than those trained from the general domain corpora for
      any downstream biomedical NLP task.

PMID- 30217671
TI  - Trabectedin and olaparib in patients with advanced and non-resectable bone and
      soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian
      Sarcoma Group.
AB  - BACKGROUND: Trabectedin is an alkylating drug with a unique mechanism of action
      causing single-strand and double-strand DNA breaks that activate DNA damage
      response pathways. Based on our preclinical data, we hypothesised that poly(ADP
      ribose) polymerase 1 (PARP1) inhibitors might be an ideal partner of trabectedin
      and aimed to assess the safety, identify the recommended phase 2 dose, and
      explore preliminary signs of activity of trabectedin and olaparib combination
      treatment in patients with bone and soft-tissue sarcoma. METHODS: We did an open
      label, multicentre, phase 1b study, recruiting patients from the national Italian
      sarcoma network aged 18 years and older with histologically confirmed bone and
      soft-tissue sarcoma progressing after standard treatments with Eastern
      Cooperative Oncology Group performance status of 1 or less. In a classic 3 + 3
      design, patients received a 24 h infusion of trabectedin on day 1 and olaparib
      orally twice a day in 21-day cycles across six dose levels (trabectedin 0.675-1.3
      mg/m2 every 3 weeks; olaparib 100-300 mg twice a day from day 1 to 21).
      Intermediate dose levels were permitted to improve safety and tolerability. The
      primary endpoint was determination of the recommended phase 2 dose (the maximum
      tolerated dose). Safety and antitumour activity were assessed in all patients who
      received at least one dose of the study drugs. We report the results of the dose
      escalation and dose-expansion cohorts. The trial is still active but closed to
      enrolment, and follow-up for patients who completed treatment is ongoing. This
      trial is registered with ClinicalTrials.gov, number NCT02398058. FINDINGS:
      Between Nov 17, 2014, and Jan 30, 2017, of 54 patients assessed for eligibility,
      we enrolled 50 patients: 28 patients in the dose-escalation cohort and 22
      patients in the dose-expansion cohort. Patients received a median of four cycles
      of treatment (IQR 2-6; range 1-17 [the patients who received the highest number
      of cycles are still on treatment]) with a median follow-up of 10 months (IQR 5
      23). Considering all dose levels, the most common grade 3-4 adverse events were
      lymphopenia (32 [64%] of 50 patients), neutropenia (31 [62%]), thrombocytopenia
      (14 [28%]), anaemia (13 [26%]), hypophosphataemia (20 [40%]), and alanine
      aminotransferase concentration increase (9 [18%]). No treatment-related life
      threatening adverse events or deaths occurred. One (2%) patient interrupted
      treatment without progression without reporting any specific toxicity. Observed
      dose-limiting toxicities were thrombocytopenia, neutropenia for more than 7 days,
      and febrile neutropenia. We selected intermediate dose level 4b (trabectedin 1.1
      mg/m2 every 3 weeks plus olaparib 150 mg twice a day) as the recommended phase 2
      dose. Seven (14%; 95% CI 6-27) of 50 patients achieved a partial response
      according to Response Evaluation Criteria In Solid Tumors 1.1. INTERPRETATION:
      Trabectedin and olaparib in combination showed manageable toxicities at active
      dose levels for both drugs. Preliminary data on antitumour activity are
      encouraging. Two dedicated phase 2 studies are planned to assess activity of this
      combination in both ovarian cancer (EudraCT2018-000230-35) and soft-tissue
      sarcomas. FUNDING: Italian Association for Cancer Research, Italian Sarcoma
      Group, Foundation for Research on Musculoskeletal and Rare Tumors, and Italian
      Ministry of Health.

PMID- 30217673
TI  - Pertuzumab therapy for HER2-positive metastatic gastric or gastro-oesophageal
      junction cancer.

PMID- 30217672
TI  - Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric
      or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind,
      randomised, placebo-controlled phase 3 study.
AB  - BACKGROUND: Adding pertuzumab to trastuzumab and chemotherapy improves survival
      in HER2-positive early breast cancer and metastatic breast cancer. We assessed
      the efficacy and safety of pertuzumab versus placebo in combination with
      trastuzumab and chemotherapy in first-line HER2-positive metastatic gastric or
      gastro-oesophageal junction cancer. METHODS: JACOB was a double-blind, placebo
      controlled, randomised, multicentre, phase 3 trial in patients aged 18 years or
      older with HER2-positive metastatic gastric or gastro-oesophageal junction
      cancer. Eligible patients had measurable or evaluable non-measurable disease at
      baseline, Eastern Cooperative Oncology Group performance status of 0 or 1, and
      baseline left ventricular ejection fraction of 55% or more. Patients at 197
      oncology clinics (in 30 countries) were randomly assigned (1:1) to receive either
      pertuzumab (840 mg intravenously) or placebo every 3 weeks, with trastuzumab (8
      mg/kg loading dose, then 6 mg/kg every 3 weeks intravenously), plus chemotherapy
      (cisplatin 80 mg/m2 every 3 weeks intravenously, oral capecitabine 1000 mg/m2
      twice a day [2000 mg/m2 every 24 h] for 28 doses every 3 weeks, or 5-fluorouracil
      800 mg/m2 every 24 h intravenously [120 h continuous infusion] every 3 weeks).
      Randomisation was by a central permuted block randomisation scheme (block size of
      4) with an interactive voice or web response system, stratified by geographical
      region, previous gastrectomy, and HER2 positivity. The primary endpoint was
      overall survival in the intention-to-treat population. This trial is registered
      with Clinicaltrials.gov, number NCT01774786 (ongoing, but closed to enrolment).
      FINDINGS: Between June 10, 2013, and Jan 12, 2016, of 3287 patients assessed, 780
      eligible patients were randomly assigned to receive either pertuzumab plus
      trastuzumab and chemotherapy (pertuzumab group, n=388) or placebo plus
      trastuzumab and chemotherapy (control group, n=392). Median duration of follow-up
      was 24.4 months (95% CI 22.3-26.1) in the pertuzumab group and 25.0 months (22.3
      28.9) in the control group. After 242 deaths in the pertuzumab group and 262
      deaths in the control group (the study was not stopped at this point), overall
      survival was not significantly different between treatment groups (median overall
      survival 17.5 months [95% CI 16.2-19.3] in the pertuzumab group and 14.2 months
      [12.9-15.5] in the control group; hazard ratio 0.84 [95% CI 0.71-1.00]; p=0.057).
      Serious adverse events occurred in 175 (45%) of 385 patients in the pertuzumab
      group and 152 (39%) of 388 patients in the control group. Diarrhoea was the most
      common serious adverse event in both groups (17 [4%] patients in the pertuzumab
      group vs 20 [5%] patients in the control group). The most common grade 3-5
      adverse events were neutropenia (116 [30%] patients in the pertuzumab group vs
      108 [28%] patients in the control group), anaemia (56 [15%] vs 65 [17%]), and
      diarrhoea (51 [13%] vs 25 [6%]). Treatment-related deaths occurred in seven (2%)
      patients in the control group; no treatment-related deaths occurred in the
      pertuzumab group. INTERPRETATION: Adding pertuzumab to trastuzumab and
      chemotherapy did not significantly improve overall survival in patients with HER2
      positive metastatic gastric or gastro-oesophageal junction cancer compared with
      placebo. Further studies are needed to identify improved first-line treatment
      options in these types of cancer and to identify patients with HER2-driven
      tumours who might benefit from dual HER2-targeted therapy. FUNDING: F. Hoffmann
      La Roche Ltd.

PMID- 30217674
TI  - TOMAS: revisiting PARP inhibitor combination therapy.

PMID- 30217675
TI  - Lymphoma of the mantle with digestive tube affection.
AB  - INTRODUCTION AND AIM: Mantle cell lymphoma is an aggressive subtype of B-cell non
      Hodgkin lymphoma and its incidence is 0.5/100,000 inhabitants. Gastrointestinal
      involvement at diagnosis is 15-30%. The aim of our study was to analyze the
      clinical and endoscopic characteristics of mantle cell lymphoma affecting the
      digestive tract. MATERIAL AND METHODS: A retrospective study was conducted, based
      on a case series of patients with mantle cell lymphoma affecting the
      gastrointestinal tract that were diagnosed over a 10-year period. RESULTS: Ten
      patients (11.7%) had gastrointestinal tract involvement. The upper endoscopic
      findings were polypoid lesions (66%), thickened folds (44%), and nonspecific
      changes in the mucosa (33%). At colonoscopy, polypoid lesions were viewed in 100%
      of the patients and ulcerated lesions in 40%. CONCLUSION: Polypoid lesions are
      the most common endoscopic characteristics in patients with mantle cell lymphoma
      of the gastrointestinal tract. Upper endoscopy and colonoscopy should be carried
      out on patients with mantle cell lymphoma, even those with nonspecific symptoms,
      to check their gastrointestinal status. Gastrointestinal involvement has an
      impact on disease staging.

PMID- 30217676
TI  - FGF23 beyond Phosphotropic Hormone.
AB  - Fibroblast growth factor (FGF) 23 is a bone-derived phosphotropic hormone that
      regulates phosphate and vitamin D metabolism. FGF23 mainly affects kidney
      function via the FGF receptor (FGFR)/alpha-Klotho complex. The physiological
      roles of FGF23 and alpha-Klotho in the regulation of mineral homeostasis have
      been well established. In addition, recent studies have reported that FGF23 has
      various effects on many other tissues, sometimes in an alpha-Klotho-independent
      manner, especially under pathological conditions. However, how FGF23 works in
      these tissues without alpha-Klotho is not entirely clear. Here we review the
      recent reports concerning the actions of FGF23 on various tissues and discuss the
      remaining questions about FGF23.

PMID- 30217677
TI  - Challenges and common weaknesses in case-control studies on drug use and road
      traffic injury based on drug testing of biological samples.
AB  - PURPOSE: To determine and discuss common weaknesses and errors in case-control
      studies on the association between drug use and road traffic crash injury among
      drivers and recommend improvements for future studies. METHODS: A search for case
      control studies published between 2000 and 2016 was performed using PubMed and
      other databases in addition to manual search. The used methodologies were
      compared with requirements and recommendations for case-control studies as well
      as current knowledge on the interpretation of drug concentrations in biological
      samples. RESULTS: Seventeen studies were identified. The major difficulties in
      the studies were related to likely selection bias, information bias, and
      confounding. In some studies, the definition of drug exposure was different for
      controls than for cases, generating potentially serious errors in the odds ratio
      estimations. Other weaknesses include lacking explanation of the assessment of
      drug exposure, missing covariates, lacking description of statistical methods,
      and lack of discussion of bias and confounding. CONCLUSIONS: Many of the observed
      challenges and weaknesses can be overcome or reduced. Recommendations for future
      studies are presented.

PMID- 30217678
TI  - Dialysis of the goat semen and its effect on the quality of frozen/thawed
      spermatozoa processed in the presence of egg yolk.
AB  - The aim of the present study was to analyze the effect of dialysis on the quality
      of frozen/thawed buck semen. Ejaculates (n = 15) from three Saanen bucks were
      divided into three experimental groups. Semen in Group Ce (centrifugation) was
      processed by standard method and washed two times at 1.085 * g for 20 min. During
      this time, the diluted control semen (Co) was stored at room temperature. Semen
      in Group D was dialyzed using 300 kDa cut-off semi-permeable cellulose tubing.
      The semen from all groups was diluted with extender containing 20% egg yolk and
      frozen in liquid nitrogen vapor. After thawing, semen samples were evaluated by
      microscopic and biochemical analyses. Phospholipase A2 was in amounts that was
      72.0 +/- 11.7% less after dialysis and 21.3 +/- 10.0% less after washing with
      centrifugation compared to the control semen (P <  0.05). Spermatozoa from Group
      Co had a lesser motility and viability and greater percentage of morphological
      abnormal spermatozoa in comparison to Groups D and Ce at 3 h after thawing and
      incubation on 37  degrees C. At the same time motility and percentage of HOST
      positive spermatozoa were greater in Group Ce compared with D (P <  0.05). There,
      however, was no difference in morphology and viability (CFDA/PI analysis) of
      spermatozoa between Ce and D group. Results from the present study suggest the
      dialysis is the promising alternative method for reducing phospholipase A2 in the
      buck semen before cryopreservation.

PMID- 30217679
TI  - Ageing reduces the reproductive performance of male white shrimp Litopenaeus
      vannamei by altering sperm intracellular Ca2+ concentrations and interfering with
      sperm apoptosis.
AB  - Although the effects of age on the reproductive performance of various
      invertebrates, including white shrimp Litopenaeus vannamei are increasingly well
      documented, the mechanisms manifesting these impacts remain poorly understood. To
      ascertain the mechanisms of age on reproductive performance, the sperm quality,
      intracellular contents of Ca2+, insemination and hatching rates, and status of
      sperm apoptosis in terms of the expression of key regulatory genes were
      investigated in 11 and 16 month old male L. vannamei. The aged male individuals
      (16 months) had lesser reproductive performance in terms of fertilization and
      hatching rates. In addition, fewer and less viable sperm were detected in aged
      shrimp, which may be due to the altered expression of apoptosis-related genes.
      Furthermore, the aged males had lesser intracellular contents of Ca2+ in the
      sperm which may decrease the capacity of these gametes to undergo a complete
      acrosome reaction. In general, due to the decrease in intracellular contents of
      Ca2+ and alterations in the process of apoptosis, aged L. vannamei have
      relatively lesser quality sperm and may, therefore, have lesser reproductive
      performance.

PMID- 30217680
TI  - Trauma care construction under the guidance of county-level trauma centers.
AB  - Severe trauma has the characteristics of complicated condition, multiple organs
      involved, limited auxiliary examinations, and difficulty in treatment. Most of
      the trauma patients were sent to primary hospitals to receive treatments. But the
      traditional mode of separate discipline management can easily lead to delayed
      treatment, missed or wrong diagnosis and high disability, which causes a high
      mortality in severe trauma patients. Therefore, if the primary hospitals,
      especially county-level hospitals (usually the top general hospital within the
      administrative region of a county), can establish a scientific and comprehensive
      trauma care system, the success rate of trauma rescue in this region can be
      greatly improved. On March 1st, 2013, Tiantai People's Hospital of Zhejiang
      Province, China set up a trauma care center, which integrated the pre-hospital
      and in-hospital trauma treatment procedures, and has achieved good economic and
      social benefits. Till March 1st, 2017, 1265 severe trauma patients (injury
      severity score >16) have been treated in this trauma center. The rescue success
      rate reached 95% and the delayed and/or missed diagnosis rate was less than 5%.
      Totally 86 severe cases of pelvic fractures with unstable hemodynamics were
      treated, and the success rate was 92%. The in-hospital emergency rescue response
      time is less than 3 min, and the time from definite diagnosis to surgery is
      within 35 min.

PMID- 30217681
TI  - Arytenoid asymmetry in opera singers.
AB  - INTRODUCTION: Otolaryngologists commonly observe asymmetrical movements of the
      arytenoid cartilages, but few authors have described the clinical implications of
      this asymmetry, especially in singers. OBJECTIVES: The aim of this study was to
      determine the epidemiological and clinical characteristics of arytenoid asymmetry
      in adduction in a group of healthy opera singers and to evaluate the impact of
      this asymmetry on the voice. PATIENTS AND METHODS: The medical charts and
      laryngeal video recordings of 245 healthy opera singers were retrospectively
      reviewed. Arytenoid asymmetry was defined in relation to the position of the
      corniculate cartilages, cuneiform cartilages and aryepiglottic angle. RESULTS:
      The subjects had a mean age of 38.54years (range: 18 to 85 years) and presented a
      male-to-female sex ratio of 1.02. About 5% of subjects had a history of smoking.
      The most common vocal symptoms were occasional dysphonia (4%), followed by vocal
      fatigue (2%) and pharyngeal dryness (2%). Arytenoid asymmetry was slightly more
      common in males (50.6%) and predominantly affected the right side (64.5%). The
      most common form of asymmetry was cuneiform asymmetry (37.5%), followed by
      aryepiglottic angle asymmetry in 33.1% of cases and corniculate asymmetry in
      29.4% of cases. Mild asymmetry was observed in the majority of cases. No
      correlation was observed between arytenoid asymmetry and vocal symptoms.
      CONCLUSION: Almost one out of two singers was likely to present arytenoid
      asymmetry in adduction. The presence of this asymmetry does not appear to be
      correlated with any vocal symptoms.

PMID- 30217682
TI  - [Cutaneous foreign body granulomas following cervico-facial arterial
      embolization: Three cases].
AB  - BACKGROUND: Foreign body granuloma is an inflammatory tissue reaction to
      exogenous material. Classically it appears on the face after aesthetic
      procedures. Herein we report for the first time three cases of facial
      granulomatous reactions to microbeads after arterial cervico-facial embolization.
      PATIENTS AND METHODS: Three patients underwent embolization of the facial
      arteries using Embogold(r) microbeads in a setting of epistaxis or tumoral
      hemostasis. Within 10 to 45 days painful, inflammatory, subcutaneous nodules
      appeared on the homolateral side of the face. Histological samples showed an
      inflammatory response with giant cells as well as the presence of microbeads in
      the skin. A favorable outcome was achieved with colchicine in one patient and
      with surgery in another; the third patient was lost to follow-up. DISCUSSION: The
      embolizing microspheres produced a local inflammatory reaction, with destruction
      of the vascular wall and bead migration to facial tissue leading to a
      granulomatous reaction. The occurrence of three cases within a period of few
      weeks, with several different operators and batches of products, is surprising
      considering the long-standing use of the product. There was no common comorbidity
      in the patients and no suggestion of trauma. Retrospective analysis of the
      product batches was normal. Gold staining could play a role in severe
      inflammatory response to Embogold(r) particles. CONCLUSION: These three cases
      illustrate the value of discussing potential foreign body granulomatous reaction
      in cases of facial nodules following cervico-facial embolization. Colchicine may
      offer a valuable therapeutic alternative.

PMID- 30217683
TI  - [Multiple hypochromic or achromic macules in children and risk of tuberous
      sclerosis].
AB  - AIM: To describe in a large paediatric cohort the characteristics of
      hypopigmented and depigmented (hypochromatic and achromic) macules with no clear
      diagnosis but potentially evocative of tuberous sclerosis (TS). PATIENTS AND
      METHODS: This was a retrospective multicentre study performed between 2010 and
      2017 at a reference centre for rare skin diseases; it included all children
      consulting for hypochromic and achromic macules. A descriptive analysis was made
      of the characteristics of macules with no clear diagnosis, enabling them to be
      classified in three secondary groups: TS certain, TS ruled out, TS uncertain.
      RESULTS: Of the 3300 children seen during this 7-year period 7,265 were
      consulting for hypochromic or achromic macules, with no clear diagnosis in 18
      cases: 7 girls and 11 boys of median age at 7.21 years (range: 4 months to 16
      years and 7 months). The lesions were congenital in 7 cases. The number of
      macules varied, with over 20 in some cases. The majority were in the form of ash
      leaf spots, followed by the oval form. Two children were diagnosed at clinical
      examination, and 16 underwent it is not examinations, resulting in a diagnosis of
      certain ST in 6 of these cases. No particular characteristics of the macules
      appeared to guide the clinical examination towards ST or isolated lesions. Cafe
      au-lait spots were more frequent in the group in which ST was ruled out than in
      the other two groups: 67% vs. 33% and 33%. Neurologic involvement was more common
      in children with certain or uncertain ST than in children in whom ST was ruled
      out (83% and 67% vs. 11%). CONCLUSION: No identified characteristics of stains
      enabled the clinical examination to confirm or rule out tuberous sclerosis.
      Screening for acute any signs of ST is essential. Diagnostic efficacy is enhanced
      by additional exams.

PMID- 30217684
TI  - [Vegetant cutaneous leishmaniasis: A rare clinical variant].

PMID- 30217685
TI  - [Suprapubic Nicolau syndrome following subcutaneous injection of glatiramer
      acetate].
AB  - BACKGROUND: Subcutaneous glatiramer acetate, commercialized under the name of
      Copaxone(r), is licensed for the treatment of relapsing multiple sclerosis. Its
      major adverse effects are skin reactions at the injection site. Nicolau syndrome
      is a rare but serious iatrogenic accident. Herein we report a case seen in a
      setting of change of dosage and administration rate of Copaxone(r). PATIENTS AND
      METHODS: A 64-year-old woman, treated since 2010 with daily sub-cutaneous
      injections of Copaxone(r) 20mg/L, reported the appearance of a painful, indurated
      and erythematous plaque in the suprapubic area following changeover to 40mg/mL
      injections three times weekly. The suprapubic injections were continued and ugly
      greyish spots with stellate purpuric borders appeared. Fournier gangrene was
      ruled out by means of a soft tissue scan. DISCUSSION: We report this latest case
      of Nicolau syndrome to alert readers to the non-exceptional nature of this
      complication associated with use of glatiramer acetate, particularly at a dosage
      of 40mg/L injections three times weekly. In our case, onset of Nicolau syndrome
      appears to have been favored by continued injection in areas already showing
      inflammation. Re-injection of the drug in these areas should thus be proscribed.

PMID- 30217686
TI  - [Familial chilblain lupus: Four cases spanning three generations].
AB  - BACKGROUND: Familial chilblain lupus is a hereditary form of cutaneous lupus
      erythematosus seen in young children. It shows autosomal dominant inheritance due
      to mutations in the TREX-1 gene, or, more rarely, SAMHD1 or TMEM173 (STING). It
      belongs to the type I interferonopathies, i.e. inflammatory diseases associated
      with excessive interferon production and characterized by a positive "interferon
      signature". This is a rare entity with fewer than 10 families described to date.
      We report a new family followed over several years. PATIENTS AND METHODS: The
      patients were four subjects from the same family and spanning three generations
      (a brother and sister aged 17 and 15 years, their 39-year-old mother, and their
      60-year-old grandfather). The initial cutaneous lesions on the extremities were
      described as papular, erythematous, purplish, infiltrated, hyperkeratotic,
      pruritic and/or painful. They occurred in childhood, improved during summer and
      stabilized over time. Immunological abnormalities such as positive antinuclear
      antibodies were noted. The interferon signature was positive in all patients.
      Molecular analysis of TREX-1, SAMHD1 and STING genes in both children showed no
      evidence of mutation. DISCUSSION: The cutaneous involvement was classic except
      for absence of the scarring and mutilating progression, photosensitivity and
      vasculopathy reported in other families. There was no intrafamily variability
      other than unconstant immunological abnormalities. At the molecular level, no
      mutations in the known genes were identified. A complementary molecular analysis
      is in progress. CONCLUSION: We report a new case of familial LEF, thus adding to
      knowledge about this very rare form of lupus erythematosus.

PMID- 30217687
TI  - [Cytopenia under topical imiquimod in two patients treated with oral
      hydroxyurea].
AB  - BACKGROUND: Aldara(r) is a topical immunomodulatory treatment. The risks of
      systemic passage are minimal. There have been rare reports of systemic adverse
      effects. PATIENTS AND METHODS: Case 1. Five sachets weekly of imiquimod were
      prescribed for Bowen's disease on the forearm in a patient known to have
      essential thrombocytosis under Hydrea(r). His CBC was normal (6000
      leukocytes/mm3, 2200 PMN/mm, 230,000 platelets/mm3). Imiquimod was given in 15
      sachets weekly. Fifteen day later, the patient presented bicytopenia (3000
      leukocytes/mm3, 1400 PMN/mm3, 119,000 platelets/mm3). Hydroxyurea and imiquimod
      were suspended until normalization of CBC. Hydroxyurea was resumed without
      recurrence of the bicytopenia. The patient's history included an identical
      episode following application of imiquimod. Case 2. Five sachets weekly of
      imiquimod were prescribed for actinic keratosis on the scalp in a patient known
      to have primary polycythemia under hydroxyurea. Her CBC was normal except for
      anemia (Hb 11.5g/L, 160,000 platelets/mm3, 1100 lymphocytes/mm3). Imiquimod was
      given in 12 sachets weekly. Ten days later, anemia increased (Hb 10g/dL) with
      lymphopenia (800/mm3) and thrombocytopenia (115,000/mm3). Suspension of imiquimod
      resulted in normalization of the previous CBC values. DISCUSSION: . The
      literature review identified reports of dose-dependent lymphopenia under oral
      imiquimod but not under Aldara(r). The National Pharmacovigilance Database listed
      10 cases of hematological disorders most likely caused by Aldara(r). Hydroxyurea
      may induce cytopenia, and while it was not considered the sole causative agent in
      this case, it is likely to have had a triggering role in these patients with
      blood dyscrasias. Our findings show that misuse of imiquimod carries a potential
      risk of hematologic abnormality in patients receiving concomitant hydroxyurea, a
      commonly combined drug.

PMID- 30217688
TI  - Functional and radiological results of percutaneous K-wire aided Metaizeau
      technique in the treatment of displaced radial neck fractures in children.
AB  - OBJECTIVES: The aim of the present study was to determine the radiological and
      functional results and the efficiency of paediatric radial neck fracture fixation
      following reduction with the Metaizeau technique together with percutaneous K
      wire applied under fluoroscopy to ensure minimum soft tissue damage. METHODS: The
      study included 20 patients with Judet Type 3, Type 4a and Type 4b fractures
      operated on with the Metaizeau technique aided by percutaneous K-wire between
      2007 and 2014. The mean age of the patients was 9.75 years (range, 4-13 years).
      Mean preoperative angulation was measured as 52.4 degrees  (range, 35 degrees -85
      degrees ). The average postoperative follow-up time was 34.65 months (range, 13
      84) months. Postoperative radiological evaluations were made according to the
      Ursei classification and functional assessment with the Tibone - Stoltz
      classification system. RESULTS: Radiologically, the difference between
      preoperative and postoperative radius head angulation was found statistically
      significant (p0.001). In the clinical assessment of injured and uninjured arms,
      there was no statistically significant difference between flexion-extension (p =
      0.330) and supination-pronation range of motion (p = 0.330) and carrying angles
      (p = 0.094). According to the radiological Ursei evaluation, 17 (85%) patients
      were in perfect condition and 3 (15%) were good. In the classification of Tibone 
      Stoltz, 16 (80%) patients were evaluated as perfect, 3 (15%) as good and 1 (5%)
      as fair. CONCLUSION: From the results of this study and related literature, the
      use of the Metaizeau technique in displaced radial neck fractures requiring
      surgical treatment in children can be recommended since it creates minimum damage
      to the soft tissue, is easy to apply and the results are satisfactory. LEVEL OF
      EVIDENCE: Level IV, therapeutic study.

PMID- 30217689
TI  - Effect of platelet-rich fibrin on epidural fibrosis and comparison to ADCON(r)
      Gel and hyaluronic acid.
AB  - OBJECTIVE: In this experimental study, PRF (Platelet Rich Fibrin), HA (Hyaluronic
      Acid) gel and ADCON(r) Gel were compared in terms of preventing epidural
      fibrosis. METHODS: Twenty-eight Sprague-Dawley rats (mean weight, 400-450 g) were
      divided into 4 groups. L3-L4 laminectomy was performed in each group. Following
      laminectomy, Adcon(r) Gel, HA gel and PRF were applied onto the surgery site
      locally in Group 1, 2 and 3, respectively. Group 4 was maintained as control
      without any local application. After five weeks, L3-L4 vertebrae were removed
      totally and taken to histopathological evaluation for epidural fibrosis, acute
      inflammatory cell density, chronic inflammatory cell density, hemorrhage,
      angiogenesis and new bone formation. RESULTS: Acute inflammation cell density,
      angiogenesis, and new bone formation levels were comparable among the study
      groups (p > 0.05). However, new bone formation was higher in the PRF group.
      Epidural fibrosis and chronic inflammatory cell density were significantly lower
      in the PRF group (p < 0.05). CONCLUSION: We concluded that PRF contributed to
      hemostasis and prevented epidural fibrosis.

PMID- 30217690
TI  - An Adolescent with Left Ventricular Noncompaction and Ebstein Anomaly Presenting
      with Advanced Heart Failure: Discharge from Hospital with a Biventricular Assist
      Device.

PMID- 30217692
TI  - The effects of caffeine ingestion on isokinetic muscular strength: A meta
      analysis.
AB  - OBJECTIVES: The aims of this paper are threefold: (1) to summarize the research
      examining the effects of caffeine on isokinetic strength, (2) pool the effects
      using a meta-analysis, and (3) to explore if there is a muscle group or a
      velocity specific response to caffeine ingestion. DESIGN: Meta-analysis. METHODS:
      PubMed/MEDLINE, Scopus, and SPORTDiscus were searched using relevant terms. The
      PEDro checklist was used for the assessment of study quality. A random-effects
      meta-analysis of standardized mean differences (SMDs) was done. RESULTS: Ten
      studies of good and excellent methodological quality were included. The SMD for
      the effects of caffeine on strength was 0.16 (95% CI=0.06, 0.26; p=0.003; +5.3%).
      The subgroup analysis for knee extensor isokinetic strength showed a significant
      difference (p=0.004) between the caffeine and placebo conditions with SMD value
      of 0.19 (95% CI=0.06, 0.32; +6.1%). The subgroup analysis for the effects of
      caffeine on isokinetic strength of other, smaller muscle groups indicated no
      significant difference (p=0.092) between the caffeine and placebo conditions. The
      subgroup analysis for knee extensor isokinetic strength at angular velocities of
      60 degrees s-1 and 180 degrees s-1 showed a significant difference between the
      caffeine and placebo conditions; however, no significant effect (p=0.193) was
      found at an angular velocity of 30 degrees s-1. CONCLUSIONS: This meta-analysis
      demonstrates that acute caffeine ingestion caffeine may significantly increase
      isokinetic strength. Additionally, this meta-analysis reports that the effects of
      caffeine on isokinetic muscular strength are predominantly manifested in knee
      extensor muscles and at greater angular velocities.

PMID- 30217691
TI  - Predicting Risk of Infection in Infants with Congenital Diaphragmatic Hernia.
AB  - OBJECTIVE: To predict incident bloodstream infection and urinary tract infection
      (UTI) in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We
      conducted a retrospective analysis using the Children's Hospital Neonatal
      Database during 2010-2016. Infants with CDH admitted at 22 participating regional
      neonatal intensive care units were included; patients repaired or discharged to
      home prior to admission/referral were excluded. The primary outcome was death or
      the occurrence of bloodstream infection or UTI prior to discharge. Factors
      associated with this outcome were used to develop a multivariable equation using
      80% of the cohort. Validation was performed in the remaining 20% of infants.
      RESULTS: Median gestation and postnatal age at referral in this cohort (n = 1085)
      were 38 weeks and 3.1 hours, respectively. The primary outcome occurred in 395
      patients (36%); and was associated with low birth weight, low Apgar, low
      admission pH, renal and associated anomalies, patch repair, and extracorporeal
      membrane oxygenation (P < .001 for all; area under receiver operating curve =
      0.824; goodness of fit chi2 = 0.52). After omitting death from the outcome
      measure, admission pH, patch repair of CDH, and duration of central line
      placement were significantly associated with incident bloodstream infection or
      UTI. CONCLUSIONS: Infants with CDH are at high risk of infection which was
      predicted by clinical factors. Early identification and low threshold for sepsis
      evaluations in high-risk infants may attenuate acquisition and the consequences
      of these infections.

PMID- 30217693
TI  - Effectiveness of physical therapy interventions for low back pain targeting the
      low back only or low back plus hips: a randomized controlled trial protocol.
AB  - BACKGROUND: Recent evidence suggests that physical therapy interventions
      targeting the hips may improve outcomes, including pain and disability, for
      patients with low back pain (LBP). Currently, there is conflicting data in regard
      to whether an individual with LBP needs to have a concurrent hip impairment in
      order to respond to this approach. The purpose of this clinical trial will be to
      determine the short and long-term effectiveness of physical therapy interventions
      directed at the lumbar spine only, versus lumbar spine and hip(s), in individuals
      with a primary complaint of LBP with a concurrent hip impairment. METHODS: A
      multi-center, randomized controlled trial of 76 adult individuals with a primary
      complaint of LBP, who also have at least one concurrent hip impairment.
      Participants will be randomized into the 'LBP only' or 'LBP+Hip' group. Treatment
      to the low back in both groups will be a pragmatic approach consisting of
      interventions targeting the low back without targeting the hip(s). Participants
      randomized to the LBP+Hip group will also receive a semi-prescriptive set of
      manual therapy and exercise techniques that target the hips. The primary outcome
      measures will be the modified Oswestry Disability Index and the Numeric Pain
      Rating Scale at discharge. DISCUSSION: These two treatment strategies are
      commonly utilized in physical therapy practice, but there is uncertainty which is
      superior. This trial will also help to provide a better understanding of the role
      of concurrent hip impairments in LBP. TRIAL REGISTRATION: This trial has been
      prospectively registered at clinicaltrials.gov (ID# NCT03550014,
      https://clinicaltrials.gov/ct2/show/NCT03550014) on June 7, 2018.

PMID- 30217694
TI  - Identification of parameters in systems biology.
AB  - We consider the inverse problem for the identification of the finite dimensional
      set of parameters for systems of nonlinear ordinary differential equations (ODEs)
      arising in systems biology. A numerical method which combines Bellman's
      quasilinearization with sensitivity analysis and Tikhonov's regularization is
      implemented. We apply the method to various biological models such as the
      classical Lotka-Volterra system, bistable switch model in genetic regulatory
      networks, gene regulation and repressilator models from synthetic biology. The
      numerical results and application to real data demonstrate the quadratic
      convergence.

PMID- 30217695
TI  - On the evolution of hypercycles.
AB  - In this study, we examine the process of fitness landscape evolution of the
      hypercycle system. We assume that the parameters that define the fitness
      landscape change in order to maximize the mean fitness of the system. The
      environmental influence is expressed as resource limitation: we formalize it as a
      restriction on the fitness matrix coefficients. We show that this process of
      adaptation leads to a system that is sustainable in the presence of parasites.
      Even if the parasites are harmful to the classical hypercycle, the persistence of
      the population develops under fitness landscape evolution. One of the central
      results presented in this paper is the existence of a phase transition similar to
      the "error threshold" in the Eigen model: starting from some time moment the mean
      fitness value increase to a plateau and the hypercycle structure changes. The
      evolutionary parameters that define the fitness landscape and the mean fitness
      value tend to stabilize.

PMID- 30217696
TI  - Physiological and genomic properties of Thermus tenuipuniceus sp. nov., a novel
      slight reddish color member isolated from a terrestrial geothermal spring.
AB  - Two closely related, thermophilic bacteria, designated strains YIM 76954T and YIM
      76947, were isolated from the Rehai Geothermal Field, Tengchong, Yunnan province,
      south-west China. Polyphasic approach and whole genome sequencing were used to
      determine the taxonomy status and genomic profiles of the novel strains.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that the two
      isolates were closely related to Thermus scotoductus SE-1T (97.1% sequence
      similarity), and T. amyloliquefaciens YIM 77409T (96.6%). The strains could be
      differentiated from most recognized Thermus species by their whitish to slight
      reddish colony color, distinct DNA fingerprinting profiles and low ANI values.
      Cells stained Gram-negative, rod-shaped of diameter 0.2-0.5MUm and length 1.5
      5.0MUm. Growth occurred at 50-75 degrees C, pH 6.0-9.0 and in the presence of up
      to 1.0% (w/v) NaCl concentration. Thiosulfate was found to enhance cell growth,
      besides improving the intensity of its colony color. Oxygen, nitrate, sulfur, and
      Fe(III) could be used as terminal electron acceptors for growth. MK-8 was the
      major respiratory menaquinone. Major fatty acids were iso-C17:0, iso-C15:0,
      anteiso-C17:0, and anteiso-C15:0. The genome size was 2.26Mbp with 65.5% average
      GC content. A total of 2374 genes was predicted, comprising 2322 protein-coding
      and 52 RNA genes. On the basis of the polyphasic evidence presented, it is
      proposed that strain YIM 76954T represents a novel species of the genus Thermus,
      for which the name Thermus tenuipuniceus sp. nov. is proposed. The type strain is
      YIM 76954T (=JCM 30350T=KCTC 4677T).

PMID- 30217697
TI  - Overexpression of GP73 promotes cell invasion, migration and metastasis by
      inducing epithelial-mesenchymal transition in pancreatic cancer.
AB  - Pancreatic cancer is one of the most difficult clinical cases to diagnose with a
      very low 5-year survival rate of 5%, regardless of the advances made in both the
      medical and surgical treatment of the disease. One of the contributing factors
      for the high mortality rate seen of pancreatic cancer patients is the lack of
      effective chemotherapies, which is believed to be due to drug-resistance. Based
      on recent evidence, epithelial-mesenchymal transition (ETM) of pancreatic cancer
      cells has been found to be associated with the development of drug resistance and
      an increase in cell invasion. Therefore, we conducted the present study in order
      to investigate the regulatory effects of Golgi protein-73 (GP73) on PC. GP73 and
      EMT-related gene expressions in PC, along with the adjacent and chronic
      pancreatitis tissues were determined by means of RT-qPCR and Western blot
      analysis. Cultured PC cells were treated with pAdTrack-CMV, si-NC, GP73
      overexpression, Si-GP73, Snail-siRNA and GP73 + Snail-siRNA. Cell invasion,
      migration and metastasis were measured in vitro and in vivo. The results revealed
      that the PC tissues and chronic pancreatitis tissues exhibited diminished E
      cadherin expression and amplified GP73, N-cadherin, Vimentin and Snail
      expression. In response to GP73 gene silencing, PC cells presented with increased
      E-cadherin expression and decreased N-cadherin, Vimentin, Snail expression in
      addition to the inhibition of the number of invasive cells, tumor volume and
      number of liver lesions. These findings highly indicated that the overexpression
      of GP73 promotes cell invasion, migration and metastasis by inducing EMT in PC.

PMID- 30217698
TI  - Three-dimensional analysis of the vestibulo-ocular reflex and the ability to
      distinguish the direction of centripetal acceleration in humans during eccentric
      rotation with the right ear facing downwards.
AB  - This study was conducted to evaluate the linear vestibulo-ocular reflex (lVOR)
      mediated by the saccule, and to investigate the relationship between the lVOR and
      the ability to distinguish the direction of centripetal acceleration during
      centric and eccentric rotation. Participants sat on a chair in darkness, with the
      right ear facing downwards, either directly above the center of rotation, or with
      their nose out, nose in, right shoulder out, or left shoulder out against the
      center of rotation (eccentric rotation). Participants were given no information
      about the chair position, and were rotated sinusoidally at 0.1-0.7 Hz. Three
      dimensional eye movements during rotation were analyzed. Participants were asked
      to describe the position of the chair after rotation. Correctly reporting the
      five possible chair positions requires recognition of the direction of
      centripetal acceleration. We analyzed the rate of correct answers to assess
      participants' ability to identify the direction of centripetal acceleration. lVOR
      mediated by the saccule was observed only at high rotational frequencies. The
      rate of correct answers was higher at high rotational frequencies than that at
      low rotational frequencies. These results indicate that high rotational frequency
      is important for both lVOR mediated by the saccule and distinguishing the
      direction of centripetal acceleration.

PMID- 30217699
TI  - A daily multidisciplinary assessment of older adults undergoing elective
      colorectal cancer surgery is associated with reduced delirium and geriatric
      syndromes.
AB  - OBJECTIVES: Comprehensive geriatric assessment (CGA) has shown to benefit older
      patients undergoing urological and orthopedic surgery. However, this approach has
      been scarcely assessed in patients elected for colorectal surgery. MATERIALS AND
      METHODS: Retrospective cohort of patients aged >=70 years admitted for elective
      colorectal cancer surgery to a single hospital between 2008 and 2012. Upon
      admission, patients were assigned to a usual care (UC) plan or a CGA-based care
      (GS) plan conducted by a multidisciplinary team, according to standard clinical
      criteria.Analyzed outcomes included the incidence of delirium and other geriatric
      syndromes during hospital stay, mortality, readmissions, andnumber of
      perioperative complications. RESULTS: The cohort included 310 patients, 203
      assigned to the GS group and 107 to the UC group. Patients in the GS group had
      significantly lower Barthel and Lawton scores, higher prevalence of dementia and
      heart failure, and higher comorbidity burden. Fifty-four (17.5%)
      patientsexperienced delirium (23 [11.3%] and 31 [29.2%] in the GS and UC groups,
      respectively; p < .001), and 49 (15.8%) patient experienced other geriatric
      syndromes (21 [10.3%] and 28 [26.2%] in the GS and UC groups, respectively; p <
      .001). Serious complications were more frequent in the GS group: 154 (75.9%) vs
      60 (56.1%) in the UC group; p < .001. No significant differences were observed
      between groups regarding readmissions, and in-hospital and post-discharge (1 year
      follow-up) mortality. CONCLUSIONS: Despite the poorer clinical condition of
      patients in the GS group, the CGA-based intervention resulted in a lower
      incidence of delirium and other geriatric syndromes compared with the UC group.

PMID- 30217700
TI  - Laparoscopic liver resection for segment VII hepatocellular carcinoma in a
      cirrhotic patient (with video).

PMID- 30217701
TI  - Claims Variability in Charges and Payments for Common Open and Endovascular
      Procedures.
AB  - BACKGROUND: Cost-effectiveness in healthcare is being increasingly scrutinized.
      Data regarding claims variability for vascular operations are lacking. Herein, we
      aim to describe variability in charges and payments for aortoiliac (AI) and
      infrainguinal (II) revascularizations. METHODS: We analyzed 2012-2014 claims data
      from a statewide claims database for procedures grouped by Current Procedural
      Terminology codes into II-open (II-O), II-endovascular (II-E), AI-open (AI-O),
      and AI-endovascular interventions (AI-E). We compared charges and payments in
      urban (>=50,000 people, UAs) versus rural areas (<50,000 people, RAs). Amounts
      are reported in $US as median with interquartile range. Cost-to-charge ratios
      (CCRs) as a measure of reimbursement were calculated as the percentage of the
      charges covered by the payments. Wilcoxon rank-sum tests were performed to
      determine significant differences. RESULTS: A total of 5,239 persons had complete
      claims data. There were 7,239 UA and 6,891 RA claims, and 1,057 AI claims (AI-E =
      879, AI-O = 178) and 4,182 II claims (II-E = 3,012, II-0 = 1,170). Median charges
      were $5,357 for AI [$1,846-$27,107] and $2,955 for II [$1,484-$9,338.5] (P <
      0.0001). Median plan payment was $454 for AI [$0-$1,380] and $454 for II [$54
      $1,060] (P = 0.67). For AI and II, charges were significantly higher for UA than
      RA (AI: UA $9,875 [$2,489-$34,427], RA $3,732 [$1,450-$20,595], P < 0.0001; II:
      UA $3,596 [$1,700-$21,664], RA $2,534 [$1,298-$6,169], P < 0.0001). AI-E charges
      were higher than AI-O (AI-E $7,960 [$1,699-$32,507], AI-O $4,774 [$2,636-$7,147],
      P < 0.0001), but AI-O payments were higher (AI-E $424 [$0-$1,270], AI-O $869
      [$164-$1,435], P = 0.0067). II-E charges were higher (II-E $2,994 [$1,552
      $22,164], II-O $2,873 [$1,108-$5,345], P < 0.0001), but II-O payments were higher
      (II-E $427 [$50-$907], II-O $596 [$73-$1,299], P < 0.0001). CCRs were highest for
      II operations and UAs. CONCLUSIONS: Wide variability in claim charges and
      payments exists for vascular operations. AI procedures had higher charges than
      II, without any difference in payments. UA charged more than RA for both AI and
      II operations, but RA had higher payments and CCRs. Endovascular procedures had
      higher charges, while open procedures had higher payments. Charge differences may
      be related to endovascular device costs, and further research is necessary to
      determine the reasons behind consistent claims variability between UA and RA.

PMID- 30217702
TI  - Emergency Endovascular Management of a Symptomatic Pseudoaneurysm of the Left
      Subclavian Artery Ostium Using a Combination of an Abdominal Aortic Stent-Graft
      Extension Cuff and a Periscope Stent Graft.
AB  - A pseudoaneurysm located at the subclavian artery ostium is an infrequent but
      life-threatening pathology that usually requires major thoracic surgery with a
      high risk of mortality and morbidity. Endovascular therapy applied to the aortic
      arch branches is a recent alternative technique, which is still in its early
      stages because dedicated endovascular devices for the aortic arch are lacking. In
      this article, we present the emergency endovascular management of a symptomatic
      pseudoaneurysm of the left subclavian artery ostium which was presumably
      secondary to an atherosclerotic plaque rupture. Endovascular exclusion required a
      combination of an abdominal aortic stent-graft extension cuff, which was placed
      via a retroperitoneal iliac access, and a subclavian artery periscope stent
      graft.

PMID- 30217703
TI  - Safety and Effectiveness of Suture-mediated Arterial Closure Device in
      Hepatocellular Carcinoma Patients Who Underwent Drug-Eluting Beads Transarterial
      Chemoembolization.
AB  - BACKGROUND: The number of transarterial percutaneous procedures has risen over
      the years, consequently reducing puncture site related complications has become a
      necessity. To this end, the use of arterial closure devices has been growing
      progressively and their benefits have become a focus of research. The purpose of
      this study is to assess the safety and effectiveness of a suture-mediated closure
      device, Perclose ProGlide(r) (Abbott Vascular, Redwood City, CA), in patients
      with liver disease and hepatocellular carcinoma who underwent transarterial liver
      chemoembolization with drug-eluting beads. MATERIALS AND METHODS: A cohort of 253
      hepatocellular carcinoma patients who underwent 449 procedures of transarterial
      liver chemoembolization with drug-eluting beads using the Perclose Proglide
      device was prospectively studied. The main endpoints evaluated were the technical
      success of the device, defined as complete hemostasis achieved within 3 min after
      the closure, and the incidence of puncture-site complications. The secondary
      endpoints evaluated were the correlation between epidemiological factors,
      coagulation profile and degree of liver disease, and the occurrence of
      complications. RESULTS: Technical success was achieved in 96% of the cases. Among
      patients who underwent repeated procedures using the same vascular access, this
      rate was 95.3%. Puncture-site complications were observed in 7 procedures
      (1.56%); 4 (0.89%) were due to hemorrhage, 2 (0.44%) hematomas and 2 (0.44%)
      pseudoaneurysms; 2 (0.44%) due to limb ischemia; and 1 (0.22%) due to arterial
      dissection. Among them, 3 cases required intervention. The statistical analysis
      of demographic characteristics, Child-Pugh classification, and coagulation status
      did not show a significant correlation with the occurrence of complications. Of
      the 449 procedures, only 4 (0.89%) needed hospitalization due to puncture-site
      complications. CONCLUSIONS: The use of Perclose Proglide is safe and effective in
      patients with liver disease and hepatocellular carcinoma who underwent
      transarterial liver chemoembolization with drug-eluting beads.

PMID- 30217704
TI  - Popliteal Angiosarcoma after Bypass with Autologous Saphenous Vein.
AB  - Angiosarcoma (AS) is a type of malignancy within sarcomas affecting soft tissue
      and bone. It presents a very heterogeneous distribution in the human body, and it
      can appear in multiple locations, from breast to liver or skin. The incidence of
      this type of tumor is low; however, it is aggressive and requires an early
      diagnosis to initiate the treatment as soon as possible. In the present article,
      we report the case of a male patient who was diagnosed with epithelioid AS of
      popliteal artery after an aneurysm popliteal surgery, as well as its treatment
      and evolution. This kind of tumors has controversial treatment and poor survival
      rates in the early years.

PMID- 30217705
TI  - Safety and Effectiveness of Retrograde Arterial Access for Endovascular Treatment
      of Critical Limb Ischemia.
AB  - BACKGROUND: Retrograde arterial access (RA) of the popliteal, tibial, or pedal
      arteries may facilitate endovascular treatment of complex infrainguinal lesions
      in patients with critical limb ischemia (CLI). Here, we assess the safety and
      efficacy of this technique. METHODS: A retrospective review of prospectively
      collected institutional data (consecutive M2S entries) was performed to identify
      patients with CLI undergoing peripheral vascular intervention from February 2012
      through December 2017. Demographics, comorbidities, procedural characteristics,
      and outcomes were analyzed, and comparisons were made between outcomes of
      patients undergoing RA and those undergoing a standard antegrade access (SA)
      approach. RESULTS: Five hundred sixty-six patients were identified, of whom 26
      (4.6%) underwent RA. Of these, 4 were accessed via the popliteal artery (15.4%),
      13 via the tibial vessels above the ankle (50.0%), and 9 via pedal vessels
      (34.6%). RA facilitated procedural success in 96.2% of cases. There were no
      instances of distal embolization, perforation, or loss of distal target with RA.
      Primary, primary assisted, and secondary patency rates were consistently lower
      for RA patients than for SA patients, as was limb salvage and amputation-free
      survival. No difference was seen in overall survival. CONCLUSIONS: RA represents
      a viable and safe option for revascularization when SA fails. Although outcomes
      are poorer than SA, this technique can be useful in CLI patients, especially when
      open surgical revascularization is not an option.

PMID- 30217706
TI  - Intraoperative Heparin Use during Upper Extremity Arteriovenous Access Creation
      Does Not Affect Outcomes.
AB  - BACKGROUND: There are conflicting data about the effect of heparin use on
      perioperative outcomes during upper extremity arteriovenous (AV) access creation.
      Our goal was to assess the effect of the use and degree of intraoperative heparin
      on perioperative outcomes after AV access creation. METHODS: All upper extremity
      AV access cases performed at a tertiary academic medical center between 2014 and
      2017 were reviewed. Patient and procedural details including intraoperative
      heparin use and dosing as well as protamine use were analyzed. Full heparin dose
      was defined as 80-100 U/kg and partial heparin dose as less than 80 U/kg.
      Perioperative arterial thrombosis or distal embolism, hematoma, and early loss of
      primary patency within 30 days were evaluated. Multivariate analysis was
      performed to assess the effect of heparin use. RESULTS: There were 550 AV access
      cases identified: brachiocephalic (37.5%), brachiobasilic (29.3%), and
      radiocephalic fistulas (12.9%), and AV grafts (16.9%). Average patient age was
      62.6 years and 58.9% were male. Full heparinization was used in 21.3%, partial
      heparinization in 58.7%, and no heparin was used in 20% of cases. Protamine was
      used in 94.9% of full heparin cases and 51.4% of partial heparin cases. No
      perioperative arterial thrombosis or distal embolism was observed. Perioperative
      wound hematoma rate was 3.4%, 3.1%, and 0.9% in full heparin, partial heparin,
      and no heparin cohorts, respectively (P = 0.42). Early loss of primary patency
      was 11.1%, 7.7%, and 6.4% for full heparin, partial heparin, and no heparin
      cases, respectively (P = 0.39). There were no differences in return to the
      operating room or perioperative survival. On multivariable analysis, full heparin
      use (odds ratio [OR] 3.82, 95% confidence interval [CI] 0.41-35.9, P = 0.24) and
      partial heparin (OR 4.03, 95% CI 0.5-32.6, P = 0.19) use were not significantly
      different from no heparin cases with respect to 30-day perioperative hematoma
      rate. Full heparin (OR 1.76, 95% CI 0.65-4.78, P = 0.26) and partial heparin (OR
      1.13, 95% CI 0.46-2.75, P = 0.79) were not significantly different from no
      heparin cases with respect to early loss of primary patency. CONCLUSIONS:
      Intraoperative heparin use, at full or partial doses, did not affect
      perioperative outcomes after AV access creation. Overall complication event rate
      was low for all groups. AV access can be safely performed without intraoperative
      heparin use.

PMID- 30217707
TI  - Usefulness of the Clavien-Dindo Classification to Rate Complications after
      Carotid Endarterectomy and Its Implications in Patient Prognosis.
AB  - BACKGROUND: Our primary objective was to test if the Clavien-Dindo classification
      (C-D-C) is also applicable for the assessment of carotid surgery and how well it
      correlates with patient prognosis in the mid-term follow-up. METHODS: From
      January 2011 to March 2014, a total of 248 consecutive open surgical carotid
      revascularization procedures were performed at one academic institution. All
      patients, symptomatic and asymptomatic, had a high-grade (>70%) stenosis and were
      operated on under general anesthesia. Physicians graded all complications that
      were identified in the first 30 days after surgery according to C-D-C.
      Complications were considered "minor" if they were of C-D-C grades I or II.
      Complications were considered "major" if they were of C-D-C grades III (those
      requiring surgical, endoscopic, or radiological intervention) or IV (those that
      are life-threatening). RESULTS: In the analysis of the overall survival, we have
      found the following differences: (1) survival at 12 months (no complication [NC]:
      96.3%, minor complications [Cmin]: 94.3%, major complications [Cmaj]: 85.7%), (2)
      at 24 months (NC: 93.1%, Cmin: 92.8%, Cmaj: 64.3%), and (3) at 36 months (NC:
      87.7%, Cmin: 81.7%, Cmaj: 64.3%). These differences were significant (P = 0.014).
      When analyzing the stroke-free survival after surgery, the survival rates were as
      follows: (1) at 12 months (NC: 94.2%, Cmin: 91.3%, Cmaj: 84.6%), (2) at 24 months
      (NC: 87.7%, Cmin: 82.3%, Cmaj: 61.5%), and (3) at 36 months (NC: 81.13%, Cmin:
      76.5%, Cmaj: 61.5%). The significance of the difference is P = 0.016. In the
      analysis of cardiovascular event-free survival, taking into account not only
      stroke and myocardial infarction but also major amputation, the survival analysis
      shows the following results: (1) at 12 months (NC: 90.3%, Cmin: 76.1%, Cmaj:
      60%), (2) at 24 months (NC: 81.1%, Cmin: 61.1%, Cmaj: 50%), and (3) at 36 months
      (NC: 73%, Cmin: 56.8%, Cmaj: 0%). These data also show a difference between the
      groups (P < 0.001). CONCLUSSIONS: The C-D-C is applicable for patients who
      underwent a carotid endarterectomy, and the classification seems to make a good
      correlation of the grade of the complication and the prognosis during follow-up.
      More studies are needed with larger numbers of patients and longer follow-up
      times to clarify the use of the C-D-C after vascular surgery and identify high
      risk patients. It can also be helpful to homogenize reports and make them
      comparable.

PMID- 30217708
TI  - Outcomes after Lower Extremity Revascularization for Treatment of Critical Limb
      Ischemia with Tissue Loss in Patients with Chronic Immune-Mediated Inflammatory
      Disease.
AB  - BACKGROUND: To evaluate outcomes after lower extremity revascularization for
      critical limb ischemia with tissue loss in patients with chronic immune-mediated
      inflammatory disease. METHODS: A retrospective medical record review of all lower
      extremity revascularization for critical limb ischemia with tissue loss at a
      university-affiliated hospital over a 3-year period was completed for
      demographics, comorbidities, lower extremity revascularization indication,
      angiogram results, complications, mortality, limb salvage, and reintervention.
      Chronic immune-mediated inflammatory disease (CIID) and control (no autoimmune
      disease) were compared by chi-squared test, Student's t-test, Kaplan-Meier, and
      Cox Regression. RESULTS: There were 349 procedures performed (297 patients): (1)
      44 (13%) primary amputations and (2) 305 (87%) lower extremity
      revascularizations, in which 83% were endovascular interventions; 12% was bypass;
      and 5% was hybrid, in which 40% was infrainguinal and 60% was infrageniculate,
      72% Wounds Ischemia Infection Score System (WIFi) tissue loss class 2-3, 35%
      CIID. No differences were noted between CIID and control for primary amputation
      (P = 0.11), lower extremity revascularization type (P = 0.50), or lower extremity
      revascularization anatomic level (P = 0.43). Mean age was 71 + 13 years, and 56%
      of the patients were of male gender. Those with CIID were of similar age as
      controls (71 +/- 14 vs. 71 +/- 13; P = 0.87) and presented with comparable
      runoff: (1) <=1 vessel (52% vs. 47%; P = 0.67), (2) WIFi tissue loss
      classification class 2-3 (66% vs. 76%; P = 0.09), and (3) WIFi infection
      classification class 2-3 (29% vs. 30%; P = 0.9). They were also less likely to be
      male (47% vs. 61%; P = 0.022) or current smokers (13% vs. 27%; P = 0.008).
      Postoperative mortality (P = 0.70) morbidity and reoperation (0.31) were
      comparable. Twenty-four-month survival was similar for CIID and control (83% +/-
      5% vs. 86% + 3%; P = 0.78), as was the amputation-free interval (69% +/- 5% vs.
      61% +/- 4%; P = 0.18) and need for target extremity revascularization (40% vs.
      53%; P = 0.04). Use of steroids and other anti-inflammatory medications was
      associated with improved 24-month amputation-free interval (87% +/- 9% vs. 63% +/
      3%; P = 0. 05). Dialysis (odds ratio: 2.6; 1.5-4.7; P = 0.001), WIFi infection
      class 2-3 (odds ratio: 2.8; 1.6-4.9; P < 0.001), prerunoff vessel (0-1 vs. 2-3)
      to the foot (odds ratio: 0.52; 0.37-0.73; P < 0.001), steroids/other anti
      inflammatory agents (0.29; 0.06-0.96; P = 0.04), and statins (0.44; 0.25-0.77; P
      = 0.005) were independent predictors of 24-month amputation-free interval (Cox
      proportional hazard ratio). CONCLUSIONS: Patients with critical limb ischemia,
      tissue loss, and concomitant CIID can be successfully treated with lower
      extremity revascularization with similar limb salvage and need for
      reintervention. Steroid/anti-inflammatory use appears beneficial.

PMID- 30217709
TI  - Factors Associated with Ipsilateral Limb Ischemia in Patients Undergoing Femoral
      Cannulation Extracorporeal Membrane Oxygenation.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an important life
      saving modality for patients with cardiopulmonary failure. Vascular
      complications, including clinically significant limb ischemia, may occur as a
      result of femoral artery cannulation for venoarterial (VA) ECMO. This study
      examines our institutional experience with femoral VA ECMO and the development of
      ipsilateral limb ischemia. METHODS: We performed a retrospective review of all
      consecutive patients undergoing femoral VA ECMO between 2011 and 2016. The
      primary endpoint was clinical evidence of limb-threatening ischemia. Multivariate
      logistic regression analysis was used to identify predictors for limb ischemia
      after cannulation. RESULTS: Between March 2011 and September 2016, 154 patients
      underwent femoral cannulation for VA ECMO. Overall in-hospital mortality was
      59.7%. Clinically significant ipsilateral limb ischemia occurred in 34 (22%)
      patients; 7 required four-compartment fasciotomy, and 3 of these patients
      required amputation. On univariate analysis, a history of pulmonary disease,
      peripheral arterial disease, and stroke or transient ischemic attack was
      significantly associated with clinical limb ischemia. On multivariate analysis,
      younger age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.93-0.99),
      diabetes (OR, 2.77; 95% CI, 1.08-7.12), pulmonary disease (OR, 3.86; 95% CI, 1.38
      10.78), and peripheral arterial disease (OR, 13.68; CI, 2.75-68.01) were
      associated with limb ischemia. Lack of prophylactic distal perfusion catheter and
      arterial cannula size were not independently associated with limb ischemia.
      CONCLUSIONS: Femoral ECMO cannulation can be associated with significant limb
      ischemia necessitating surgical intervention. Younger patients, as well as those
      with a history of diabetes, pulmonary disease, and peripheral arterial disease,
      may be at increased risk for this complication.

PMID- 30217710
TI  - Length of Stay after Thoracic Endovascular Aortic Repair Depends on Indication
      and Acuity.
AB  - BACKGROUND: Length of stay (LOS) is a commonly used metric to optimize value in
      medical care. Although pathways have been developed for some procedures in
      vascular surgery to reduce LOS, they do not yet exist for thoracic endovascular
      aortic repair (TEVAR). The purpose of this study is to identify and define the
      risk factors for prolonged LOS in patients undergoing TEVAR to facilitate pathway
      development. METHODS: We included TEVAR patients in the National Surgical Quality
      Improvement Program database from 2005 to 2015. Prolonged LOS was defined as LOS
      > 75th percentile of the overall cohort (11 days). Because initial analysis
      revealed the distinct clinical differences between dissection and aneurysm
      patients, further analysis was stratified by aortic pathology. Student's t-test
      and Chi-square tests were used to compare demographic and perioperative variables
      between dissection and aneurysm patients, respectively. Multivariable logistic
      regression was used to evaluate the predictors for prolonged LOS. RESULTS: A
      total of 3,021 patients underwent TEVAR, with 858 patients (28.4%) undergoing
      TEVAR for dissection and 2,163 (71.6%) undergoing TEVAR for aneurysm. An initial
      analysis with logistic regression identified dissection indication (odds ratio
      [OR], 2.87; 95% confidence interval [CI], 1.1-7.3) as an independent predictor of
      prolonged LOS. Further analysis for prolonged LOS was subsequently performed
      separating dissection and aneurysm patients. Aneurysm patients were older (71.2
      +/- 11.7 vs. 63.1 +/- 13.6 years, P < 0.001), more often Caucasian (76.8% vs.
      61.8%, P < 0.001), and had more medical comorbidities (chronic obstructive
      pulmonary disease, cardiac history, diabetes, peripheral vascular disease,
      transient ischemic attack [TIA], P < 0.001). In contrast, dissection patients had
      higher American Society of Anesthesiology (ASA) classification score (58.5% had
      >3 ASA vs. 45.5%, P < 0.001), longer hospitalizations (10.2 +/- 9.3 vs. 8.5 +/-
      10.4 days, P < 0.001), were more likely to have been transferred from another
      hospital or emergency room (58.4% vs. 48.3%, P < 0.001), and were more often
      emergent (32.4% vs. 15.4%, P < 0.001). In dissection patients, ASA classification
      score (OR, 1.49; 95% CI, 1.1-2.1) and dialysis (OR, 1.98; 95% CI, 1.0-3.9) were
      independent predictors for prolonged LOS. In aneurysm patients, dependent
      functional status (OR, 2.03; 95% CI, 1.4-2.8), diabetes (OR, 1.75; 95% CI, 1.1
      2.8), cardiac history (OR, 1.37; 95% CI, 1.0-1.9), emergency status (OR, 1.98;
      95% CI, 1.4-2.8), and dialysis (OR, 2.08; 95% CI, 1.2-3.7) predicted prolonged
      LOS. Postoperative complications including stroke/TIA; failure to wean from
      ventilator, sepsis, and pneumonia; and need for reoperation similarly increased
      LOS in both dissection and aneurysm patients. CONCLUSIONS: Dissection and
      aneurysm patients undergoing TEVAR are comprised of different patient
      populations, with dissection patients more often enduring prolonged
      hospitalizations. In contrast, TEVAR performed for nonemergent aneurysm repair
      had the shortest LOS. These data support the development of separate pathways
      defined by indication and acuity for patients undergoing TEVAR.

PMID- 30217711
TI  - Outcomes of a Polytetrafluoroethylene Hybrid Vascular Graft with Preloaded
      Nitinol Stent at the Venous Outflow for Dialysis Vascular Access.
AB  - BACKGROUND: To evaluate outcomes and patency of arteriovenous grafts (AVGs)
      created using Gore hybrid vascular grafts in hemodialysis patients with limited
      venous outflow or challenging anatomy. MATERIALS AND METHODS: A retrospective
      review was performed in two academic centers of all patients between July 2013
      and December 2016 who underwent surgical AVG creation using a Gore hybrid
      vascular graft in a brachial artery to axillary configuration. Patient
      characteristics and comorbidities as well as graft patency, function, and
      subsequent need for percutaneous interventions were recorded. RESULTS: Forty-six
      patients including 30 females (65.2%) and 16 males (34.8%) with a mean age of 63
      +/- 13 years were identified. The most common indications for a hybrid vascular
      graft were limited surgical accessibility and/or revision of existing AVG due to
      severe stenotic lesions at the venous outflow in 33 patients (72%). One-year
      primary unassisted and assisted patency rates were 44 +/- 8% and 54 +/- 8%,
      respectively, compared with 1-year secondary patency rate of 66 +/- 8%. The rate
      of percutaneous interventions to maintain graft function and patency was
      approximately one intervention per graft per year. CONCLUSIONS: Access created
      with the hybrid vascular graft in a brachial-axillary (brachial artery to
      axillary vein) configuration is an acceptable option for patients with limited
      venous outflow reserve and challenging anatomy. Twelve-month primary and
      secondary patency rates and need for percutaneous interventions were comparable
      to traditional AVGs.

PMID- 30217712
TI  - Clinical Features and Management of "Phlebitis-like Abnormal Reaction" After
      Cyanoacrylate Closure for the Treatment of Incompetent Saphenous Veins.
AB  - BACKGROUND: Cyanoacrylate closure for the treatment of incompetent saphenous
      veins does not cause thermal damage and demonstrates satisfactory outcomes with
      rapid recovery. However, the characteristics of phlebitis-like abnormal reaction
      (PLAR), the most common adverse event after cyanoacrylate closure, have not been
      clarified. Moreover, it differs from typical phlebitis after thermal ablation.
      The objective of our study is to investigate the clinical features of PLAR after
      cyanoacrylate closure and to report its management. METHODS: A total of 160
      patients with 271 incompetent saphenous veins (great saphenous veins, 201; small
      saphenous veins, 70) underwent cyanoacrylate closure with the VenaSealTM system.
      We defined PLAR as any unusual skin condition that develops suddenly, such as
      erythema, itching, swelling, and pain/tenderness, over the treated veins several
      days after cyanoacrylate closure. Oral antihistamines and intravenous
      dexamethasone were administered to manage PLAR. RESULTS: Of the 271 treated
      veins, 69 experienced PLAR (25.4%). The mean time of occurrence was 13.6 +/- 4.6
      days after treatment. The rate of occurrence of erythema, itching, swelling, and
      pain/tenderness were 92.2%, 91.2%, 66.2%, and 48.5%, respectively. The occurrence
      of PLAR was significantly higher for great saphenous veins than for small
      saphenous veins (P < 0.001). Occurrences were more frequent in cases with a
      suprafascial great saphenous vein of length >10 cm than in cases with a
      subfascial great saphenous vein (P = 0.001). The proportion of patients who
      reported swelling decreased by more than half after the administration of oral
      antihistamine. The pain score on the 10th day also decreased significantly after
      the administration of antihistamine (P = 0.006). CONCLUSIONS: PLAR must be
      distinguished from classic phlebitis. We believe that PLAR is a type IV
      hypersensitivity reaction due to a foreign body, and in our experience,
      antihistamines or steroids are effective for the prevention and management of
      PLAR.

PMID- 30217713
TI  - Endovascular Repair of Anomalous Splenic Artery Aneurysm with Systemic Lupus
      Erythematosus.
AB  - Splenic artery aneurysm with systemic lupus erythematosus is rare but serious. We
      report a case of a 45-year-old female with systemic lupus erythematosus who
      presented with a splenic artery aneurysm of anomalous origin from the superior
      mesenteric artery. This is the first time to report about using an endovascular
      approach to treat splenic artery aneurysm combined with systemic lupus
      erythematosus. Endovascular repair of the aneurysm was conducted using a covered
      stent and multiple coils to exclude both the aneurysm and total splenic artery
      embolization for treating thrombocytopenia, and this approach was determined to
      be safe and effective for yielding short-term results.

PMID- 30217714
TI  - Intravascular Ultrasound in Venous Thoracic Outlet Syndrome.
AB  - BACKGROUND: Venous thoracic outlet syndrome (vTOS) is a rare disease with no
      defined guidelines regarding treatment. Patients with first rib resection with
      anterior scalenectomy (FRRS) often have residual subclavian vein stenosis. The
      aim of this study was to evaluate the use of intravascular ultrasound (IVUS) in
      the treatment of vTOS patients who have been surgically decompressed with FRRS.
      METHODS: Patients treated with venography after FRRS for vTOS during 2015-2017
      were retrospectively reviewed. Patients were included if they received a venogram
      with IVUS after FRRS. The axillosubclavian vein at the site of the thoracic
      outlet was imaged using single-plane venography and IVUS. A greater than 50%
      diameter stenosis on venography or 50% cross-sectional area reduction on IVUS was
      considered significant and treated with balloon venoplasty. RESULTS: During the 2
      year period, 14 patients underwent 24 upper extremity venograms performed after
      surgical decompression for vTOS, 18 of which included IVUS. Of the 18 cases with
      IVUS, 5 (27.8%) stenoses >50% were detected by IVUS, which were not apparent on
      venography, leading to intervention. IVUS detected a greater degree of stenosis
      than venography. Seven patients required repeat venograms. Overall, IVUS detected
      significant venous stenosis in 94.4% of patients compared with 66.7% of patients
      with venography after FRRS for vTOS. CONCLUSIONS: These results suggest that IVUS
      detected greater levels of stenosis than venography, leading to more
      interventions. Just as IVUS being ideal for identifying occult iliac venous
      lesions, it may have a similar role in identifying venous lesions not evident on
      single-plane venography for postsurgical decompression in vTOS patients. Further
      studies may show this technique to increase the number of stenoses identified and
      improve long-term symptom relief.

PMID- 30217715
TI  - Endovascular Retrograde Reconstruction of the Left Renal Artery through the False
      Lumen of a Postdissection Thoracoabdominal Aortic Aneurysm-A Case Report.
AB  - Postdissection aneurysm is an indication for intervention due to high risk of
      rupture. However, the reconstruction of visceral branches involved in this
      disease, especially those perfused by a false lumen, is a tough and challenging
      task. In this article, we describe a case of successful total endovascular repair
      via retrograde reconstruction of the left renal artery through the false lumen of
      a postdissection thoracoabdominal aortic aneurysm.

PMID- 30217716
TI  - A Challenging Case of Intracardiac Leiomyomatosis Accompanied by Pseudo-Meigs
      Syndrome Originating from Uterine Leiomyoma.
AB  - BACKGROUND: Pseudo-Meigs syndrome is an unusual condition involving pelvic
      tumors, excluding ovarian fibroma, and is associated with ascites and
      hydrothorax. Pseudo-Meigs syndrome originating from uterine leiomyoma is an even
      rarer condition. Intravenous leiomyomatosis originating from uterine tumors,
      which extend from the inferior vena cava to the right heart chambers, is also
      extremely rare. CASE REPORT: This report presents an extremely rare case of
      intravenous leiomyomatosis with intracardiac extension accompanied by Pseudo
      Meigs syndrome caused by uterine leiomyoma. To the best of our knowledge, this is
      the first reported case of two different rare conditions originating
      simultaneously from one common pelvic benign tumor. We could only partially
      resect the tumor owing to its firm adherence to the vessel wall. It is crucial to
      remember that a pelvic neoplasm in a woman with various manifestations, such as
      hydrothorax, ascites, intravascular leiomyomatosis, intracardiac mass, and even
      elevated CA125 levels, does not always imply malignancy. All the accompanying
      symptoms can be resolved by simple surgical removal of the mass. CONCLUSIONS:
      Accurate preoperative assessment and detailed preparation for the surgery
      according to the nature of the tumor may yield successful results.

PMID- 30217717
TI  - Serum concentrations of perfluorinated compounds among children living in Sicily
      (Italy).
AB  - Perfluorinated compounds (PFCs) are a large group of man-made chemicals
      characterized by a completely fluorinated hydrophobic linear carbon chain
      attached to a hydrophilic head. The presence of PFCs has been related with
      various adverse effects on several organs and systems. 61 children (6-11 years of
      age) living in Sicily underwent medical examination and blood and urine routinary
      tests, as well as the serum concentration of 16 PFCs. These compounds (?PFCs =
      5.888 ng/mL, range 1.035-12.94 ng/mL) were widely detected in the samples of all
      children, showing that they had been extensively exposed to PFCs, especially
      perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA),
      perfluorohexanesulfonate (PFHxs) and perfluorodecanoic acid (PFDA). In addition,
      long-chained PFCs were found in children's blood correlated with short-chained
      ones. Perfluorodecanoic acid (PFDA) (beta=-0.114) and PFHxS (beta = 0.003) levels
      were correlated with maternal parity; while the "months of breastfeeding"
      variable is correlated with perfluoroundecanoic acid (PFUnDA) concentrations
      (beta = 0.008). Female gender is negatively associated with PFOS (beta = 0.008).
      The adverse health effects of PFCs on young children should be noted, due to
      their growing phase. Therefore, further studies are needed to monitor and address
      adverse health outcomes of PFCs on children, especially those living in
      industrial regions.

PMID- 30217718
TI  - What is the minimum length of gltA gene required for phylogenetic analyzes in
      Bartonella?
AB  - Bartonellosis is an emerging serious diseases of zoonotic relevance caused by an
      expanding number of recently discovered species of Bartonella. Many studies use
      partial gltA gene sequencing as the method of choice for species attribution, and
      a plethora of studies have utilized only this gene to describe Bartonella
      diversity. We observe a lack of correspondence between the phylogenies
      constructed using the complete gltA gene sequences and the small gene fragment
      usually used in phylogenetic analyzes. Everything indicates that important
      changes occurred by using larger fragments. Therefore, it is of great importance
      to define a minimum gltA fragment length to be used in future phylogenetic
      analyzes, besides the use of other genes.

PMID- 30217719
TI  - Development and evaluation of monoclonal antibody-based antigen capture enzyme
      linked immunosorbent assay for the diagnosis of acute leptospirosis in humans.
AB  - Monoclonal antibody (MAb)-based ELISA was developed to detect leptospiral
      antigens from the plasma of febrile patients. The MAb reacts specifically with
      pathogenic leptospires and the assay possesses excellent diagnostic test
      parameters compared to PCR, indicating that this new ELISA is useful for the
      early diagnosis of leptospirosis with low operational cost.

PMID- 30217720
TI  - FACS - based isolation of human eosinophils allows purification of high quality
      RNA.
AB  - Here we extensively describe a FACS-based protocol for isolating intact non
      stained human eosinophils from peripheral blood; a stop forward from our recently
      published initial study. This method of purification could be accomplished in <3
      h with only small volumes of whole blood necessary, even in healthy subjects
      generally exhibiting low levels of circulating eosinophils. Eosinophil activation
      during the isolation steps appeared to be minimal and this purification procedure
      yielded high quality RNA. Moreover, these FACS-isolated eosinophils had prolonged
      viability in culture and were suitable for further activation assays.

PMID- 30217722
TI  - Malignant brain tumors in patients with glutaric aciduria type I.
AB  - Three young patients with glutaric aciduria type I (age 6-23 years) of different
      ethnic origins, treated for their metabolic disease since early childhood,
      presented with malignant central nervous system tumors. We recommend continuing
      clinical follow-up, including monitoring of neurological manifestations and
      neuroradiological findings, in all patients with glutaric aciduria type I beyond
      early childhood, especially if adherence to diet is poor or the treatment was not
      started neonatally.

PMID- 30217721
TI  - Pharmacokinetics of glycerol phenylbutyrate in pediatric patients 2 months to 2
      years of age with urea cycle disorders.
AB  - INTRODUCTION: Glycerol phenylbutyrate (GPB) is approved in the US and EU for the
      chronic management of patients >=2 months of age with urea cycle disorders (UCDs)
      who cannot be managed by dietary protein restriction and/or amino acid
      supplementation alone. GPB is a pre-prodrug, hydrolyzed by lipases to
      phenylbutyric acid (PBA) that upon absorption is beta-oxidized to the active
      nitrogen scavenger phenylacetic acid (PAA), which is conjugated to glutamine
      (PAGN) and excreted as urinary PAGN (UPAGN). Pharmacokinetics (PK) of GPB were
      examined to see if hydrolysis is impaired in very young patients who may lack
      lipase activity. METHODS: Patients 2 months to <2 years of age with UCDs from two
      open label studies (n = 17, median age 10 months) predominantly on stable doses
      of nitrogen scavengers (n = 14) were switched to GPB. Primary assessments
      included traditional plasma PK analyses of PBA, PAA, and PAGN, using
      noncompartmental methods with WinNonlinTM. UPAGN was collected periodically
      throughout the study up to 12 months. RESULTS: PBA, PAA and PAGN rapidly appeared
      in plasma after GPB dosing, demonstrating evidence of GPB cleavage with
      subsequent PBA absorption. Median concentrations of PBA, PAA and PAGN did not
      increase over time and were similar to or lower than the values observed in older
      UCD patients. The median PAA/PAGN ratio was well below one over time,
      demonstrating that conjugation of PAA with glutamine to form PAGN did not reach
      saturation. Covariate analyses indicated that age did not influence the PK
      parameters, with body surface area (BSA) being the most significant covariate,
      reinforcing current BSA based dosing recommendations as seen in older patients.
      CONCLUSION: These observations demonstrate that UCD patients aged 2 months to <2
      years have sufficient lipase activity to adequately convert the pre-prodrug GPB
      to PBA. PBA is then converted to its active moiety (PAA) providing successful
      nitrogen scavenging even in very young children.

PMID- 30217723
TI  - Interval between simulated deep inspirations on the dynamics of airway smooth
      muscle contraction in guinea pig bronchi.
AB  - A certain amount of time is required to achieve a maximal contraction from airway
      smooth muscle (ASM) and stretches of substantial magnitude, such as the ones
      imparted by deep inspirations (DIs), interfere with contraction. The duration of
      ASM contraction without interference may thus affect its shortening, its
      mechanical response to DIs and the overall toll it exerts on the respiratory
      system. In this study, the effect of changing the interval between DIs on the
      dynamics of ASM was examined in vitro. Isolated bronchi derived from guinea pigs
      were held isotonically and stimulated to both contract and relax, in a randomized
      order, in response to 10-5 M of methacholine and 10-6 M of isoproterenol,
      respectively. Interference to ASM was inflicted after 2, 5, 10 and 30 min in a
      randomized order, by imposing a stretch that simulated a DI. The shortening
      before the stretch, the stiffness before and during the stretch, the post-stretch
      elongation of ASM and the ensuing re-shortening were measured. These experiments
      were also performed in the presence of simulated tidal breathing achieved through
      force fluctuations. The results demonstrate that, with or without force
      fluctuations, increasing the interval between simulated DIs increased shortening
      and post-stretch elongation, but not stiffness and re-shortening. These time
      dependent effects were not observed when ASM was held in the relaxed state. These
      findings may help understand to which extent ASM shortening and the regulatory
      effect of DI are affected by changing the interval between DIs. The potential
      consequences of these findings on airway narrowing are also discussed.

PMID- 30217724
TI  - Acute, chronic, and combined pulmonary responses to swimming in competitive
      swimmers.
AB  - The combined effects of swimming on the inspiratory muscles and pulmonary
      functions are not well known. The aim of the present study was to determine the
      acute, chronic, and combined effects of swimming on the pulmonary functions and
      respiratory muscles of competitive swimmers. Thirty males (15 in the experimental
      group [EG] and 15 in the control group [CG]) participated in this study. The EG
      subjects participated in an 8-week swim training program and performed 1 day
      before and after an 8-week 100-m swimming event. Pulmonary functions and
      respiratory muscle strength were measured immediately before and after the
      swimming event in the EG and before and after an 8-week period in the CG. The
      obtained data were analyzed using repeated measures one-way analysis of variance,
      least significant difference, and independent- and paired-sample t-tests.
      Swimming exerted negative acute effects (p < 0.05) and positive chronic effects
      (p < 0.05) on respiratory muscle strength and pulmonary functions. Further, the
      negative acute effects decreased the combined effects of the chronic and acute
      effects of swimming on respiratory muscle strength and pulmonary functions (p <
      0.05). The results indicated that swimming exerts negative acute, positive
      chronic, and combined effects on respiratory muscle strength and pulmonary
      functions.

PMID- 30217725
TI  - Bioconversion of pentose sugars to value added chemicals and fuels: Recent
      trends, challenges and possibilities.
AB  - Most of the crop plants contain about 30% of hemicelluloses comprising D-xylose
      and D-arabinose. One of the major limitation for the use of pentose sugars is
      that high purity grade D-xylose and D-arabinose are yet to be produced as
      commodity chemicals. Research and developmental activities are going on in this
      direction for their use as platform intermediates through economically viable
      strategies. During chemical pretreatment of biomass, the pentose sugars were
      generated in the liquid stream along with other compounds. This contains glucose,
      proteins, phenolic compounds, minerals and acids other than pentose sugars.
      Arabinose is present in small amounts, which can be used for the economic
      production of value added compound, xylitol. The present review discusses the
      recent trends and developments as well as challenges and opportunities in the
      utilization of pentose sugars generated from lignocellulosic biomass for the
      production of value added compounds.

PMID- 30217726
TI  - A randomized-controlled trial evaluating general endotracheal anesthesia versus
      monitored anesthesia care and the incidence of sedation-related adverse events
      during ERCP in high-risk patients.
AB  - BACKGROUND AND AIMS: ERCP is a complex procedure and often performed in patients
      at high risk for sedation-related adverse events (SRAE). However, there is no
      current standard of care with regard to mode of sedation and airway management
      during ERCP. The aim of this study was to assess the safety of general
      endotracheal anesthesia (GEA) versus propofol-based monitored anesthesia care
      without endotracheal intubation (MAC) in patients undergoing ERCP at high risk
      for SRAE. METHODS: Consecutive patients undergoing ERCP at high risk for SRAE at
      a single center were invited to participate in this randomized-controlled trial
      (NCT02850887) comparing GEA and MAC. Inclusion criteria were: STOP-BANG score of
      >=3, abdominal ascites, body mass index (BMI) >=35, chronic lung disease, ASA
      class >3, Mallampati class 4 airway, moderate to heavy alcohol use. Exclusion
      criteria were preceding EUS, emergent ERCP, tracheostomy, unstable airway,
      gastric outlet obstruction or delayed gastric emptying, and altered foregut
      anatomy. The primary endpoint was composite incidence of SRAE: (hypoxemia, use of
      airway maneuvers, hypotension requiring vasopressors, sedation-related procedure
      interruption, cardiac arrhythmia, and respiratory failure. Secondary outcomes
      included procedure duration, cannulation success, in-room time and immediate
      adverse events. RESULTS: Two hundred patients (mean age 61.1+/-13.6 years, 36.5%
      female) were randomly assigned to GEA (n=101) or MAC (n=99). Composite SRAE were
      significantly higher in the MAC group compared with GEA (51.5% vs 9.9%, p<0.001).
      This was primarily driven by the frequent need for airway maneuvers in the MAC
      group. Additionally, ERCP was interrupted in 10.1% of patients in the MAC group
      in order to convert to GEA due to respiratory instability refractory to airway
      maneuvers (n=8) or significant retained gastric contents (n=2). There were no
      statistically significant differences in cannulation, in-room, procedure or
      fluoroscopy times between the two groups. All patients undergoing GEA were
      successfully extubated in the procedure room at completion of ERCP and Aldrete
      scores in recovery did not differ between the two groups. There were no immediate
      adverse events. CONCLUSION: In patients at high risk for SRAE undergoing ERCP,
      sedation with GEA is associated with a significantly lower incidence of SRAE,
      without impacting procedure duration, success, recovery, or in-room time. These
      data suggest that GEA should be used for ERCP in patients at high risk for
      sedation-related adverse events; www.clinicaltrials.gov, (NCT02850887).

PMID- 30217727
TI  - Nasal Spray to the Rescue of Neurons in Stroke.

PMID- 30217728
TI  - Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes by
      Soluble Factors from Human Mesenchymal Stem Cells.
AB  - In this study, we proposed that the functionality or phenotype of differentiated
      cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) might
      be modified by co-culture with mesenchymal stem cells (MSCs), resulting in an
      improved therapeutic potential for failing myocardial tissues. Structural,
      motility, electrophysiological, and metabolic analyses revealed that iPSC-CMs co
      cultured with MSCs displayed aligned myofibrils with A-, H-, and I-bands that
      could contract and relax quickly, indicating the promotion of differentiation and
      the establishment of the iPSC-CM structural framework, and showed clear gap
      junctions and an electric pacing of >2 Hz, indicating enhanced cell-cell
      interactions. In addition, soluble factors excreted by MSCs, including several
      cytokines and exosomes, enhanced cardiomyocyte-specific marker production,
      produced more energy under normal and stressed conditions, and reduced reactive
      oxygen species production by iPSC-CMs under stressed condition. Notably, gene
      ontology and pathway analysis revealed that microRNAs and proteins in the
      exosomes impacted the functionality and maturation of iPSC-CMs. Furthermore, cell
      sheets consisting of a mixture of iPSC-CMs and MSCs showed longer survival and
      enhanced therapeutic effects compared with those consisting of iPSC-CMs alone.
      This may lead to a new type of iPSC-based cardiomyogenesis therapy for patients
      with heart failure.

PMID- 30217729
TI  - Upregulation of lncRNA ADAMTS9-AS2 Promotes Salivary Adenoid Cystic Carcinoma
      Metastasis via PI3K/Akt and MEK/Erk Signaling.
AB  - Neurotropic infiltrative growth and distant metastasis are the main causes of
      death in salivary adenoid cystic carcinoma (SACC) patients. Long noncoding RNAs
      (lncRNAs) are involved in many human neoplasms, however, their potential roles in
      SACC are unclear. In our study, we found that ADAM metallopeptidase with
      thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2) was
      significantly upregulated in SACC patients with metastasis and SACC-lung
      metastasis (LM) cells. Moreover, ADAMTS9-AS2 expression was closely associated
      with the prognosis and distant metastasis in SACC patients. Next, we found that c
      myc could specifically bind to the promoter of ADAMTS9-AS2 and activated its
      transcription. Knockdown of ADAMTS9-AS2 significantly inhibited migration and
      invasion of SACC cells in vitro and distant lung metastasis in vivo. Furthermore,
      ADAMTS9-AS2, which mainly expressed in the cytoplasm, shared microRNA (miRNA)
      response elements with Integrin alpha6 (ITGA6). Overexpression of ADAMTS9-AS2
      competitively bound to miR-143-3p that inhibited ITGA6 from miRNA-mediated
      degradation, and thus it activated the activity of PI3K/Akt and MEK/Erk signaling
      and facilitated SACC metastasis. In summary, ADAMTS9-AS2 promotes migration and
      invasion in SACC by competing with miR-143-3p. This sheds a new insight into the
      regulation mechanism of ADAMTS9-AS2, and it provides a possible application for
      the SACC treatment.

PMID- 30217730
TI  - Molecular Recalibration of PD-1+ Antigen-Specific T Cells from Blood and Liver.
AB  - Checkpoint inhibitors and adoptive cell therapy provide promising options for
      treating solid cancers such as HBV-related HCC, but they have limitations. We
      tested the potential to combine advantages of each approach, genetically
      reprogramming T cells specific for viral tumor antigens to overcome exhaustion by
      down-modulating the co-inhibitory receptor PD-1. We developed a novel lentiviral
      transduction protocol to achieve preferential targeting of endogenous or TCR
      redirected, antigen-specific CD8 T cells for shRNA knockdown of PD-1 and tested
      functional consequences for antitumor immunity. Antigen-specific and intrahepatic
      CD8 T cells transduced with lentiviral (LV)-shPD-1 consistently had a marked
      reduction in PD-1 compared to those transduced with a control lentiviral vector.
      PD-1 knockdown of human T cells rescued antitumor effector function and promoted
      killing of hepatoma cells in a 3D microdevice recapitulating the pro-inflammatory
      PD-L1hi liver microenvironment. However, upon repetitive stimulation, PD-1
      knockdown drove T cell senescence and induction of other co-inhibitory pathways.
      We provide the proof of principle that T cells with endogenous or genetically
      engineered specificity for HBV-associated HCC viral antigens can be targeted for
      functional genetic editing. We show that PD-1 knockdown enhances immediate tumor
      killing but is limited by compensatory engagement of alternative co-inhibitory
      and senescence program upon repetitive stimulation.

PMID- 30217732
TI  - Novel biomarkers in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related
      deaths and the fifth most common cancer worldwide. Most of these patients are
      seen with advanced disease at the time of presentation. In spite of its high
      prevalence, there are not many therapeutic options available for patients with
      advanced-stage HCC. There is an urgent need for improving early detection and
      prognostication of patients with HCC. In addition, the development of new
      therapies targeting specific pathways involved in the pathogenesis of HCC should
      be a major goal for future research, with the objective of improving outcomes of
      patients with HCC. Biomarkers represent a relatively easy and noninvasive way to
      detect and estimate disease prognosis. In spite of the numerous efforts to find
      molecules as possible biomarkers, there is not a single ideal marker in HCC. Many
      new findings have shown promising results both in diagnosing and treating HCC. In
      this review, we summarized the most recent and relevant biomarkers in HCC.

PMID- 30217731
TI  - Complement C3-Targeted Gene Therapy Restricts Onset and Progression of
      Neurodegeneration in Chronic Mouse Glaucoma.
AB  - Dysregulation of the complement system is implicated in neurodegeneration,
      including human and animal glaucoma. Optic nerve and retinal damage in glaucoma
      is preceded by local complement upregulation and activation, but whether
      targeting this early innate immune response could have therapeutic benefit
      remains undefined. Because complement signals through three pathways that
      intersect at complement C3 activation, here we targeted this step to restore
      complement balance in the glaucomatous retina and to determine its contribution
      to degeneration onset and/or progression. To achieve this, we combined adeno
      associated virus retinal gene therapy with the targeted C3 inhibitor CR2-Crry. We
      show that intravitreal injection of AAV2.CR2-Crry produced sustained Crry
      overexpression in the retina and reduced deposition of the activation product
      complement C3d on retinal ganglion cells and the inner retina of DBA/2J mice.
      This resulted in neuroprotection of retinal ganglion cell axons and somata
      despite continued intraocular pressure elevation, suggesting a direct restriction
      of neurodegeneration onset and progression and significant delay to terminal
      disease stages. Our study uncovers a damaging effect of complement C3 or
      downstream complement activation in glaucoma, and it establishes AAV2.CR2-Crry as
      a viable therapeutic strategy to target pathogenic C3-mediated complement
      activation in the glaucomatous retina.

PMID- 30217733
TI  - A case of acute septic arthritis of the hip joint caused by Panton-Valentine
      leukocidin-positive ST772 community-acquired methicillin-resistant Staphylococcus
      aureus.
AB  - Acute septic arthritis (ASA) caused by Staphylococcus aureus can lead to
      fulminant arthritis and cause permanent joint destruction. In particular,
      infection caused by methicillin-resistant Staphylococcus aureus (MRSA) becomes
      intractable and severe owing to limitation of therapeutic drugs. Here, we report
      the case of a young patient with ASA without any record of overseas travel, who
      was infected by the Panton-Valentine leukocidin-positive Bengal-Bay clone, which
      is a predominant community-acquired MRSA in India.

PMID- 30217734
TI  - Impact of alcohol-based hand sanitizers, antibiotic consumption, and other
      measures on detection rates of antibiotic-resistant bacteria in rural Japanese
      hospitals.
AB  - There are limited data available on the relationship between multidrug-resistant
      bacteria and infection control activities in small to medium-sized hospitals.
      Therefore, we collected data on the use of alcohol-based hand sanitizers (ABHSs),
      personal protective equipment, antibiotics, and the levels of detectable bacteria
      between April 2014 and March 2015 in 11 Japanese hospitals. Average total
      antibiotic consumption was 100 defined daily doses per 1000 patient-days (PD),
      and average use of ABHSs, masks, plastic aprons, and gloves was 5 L per 1000 PD,
      and 1, 2, and 26 pieces per 1 PD, respectively. Average numbers of isolated
      (isolation rate) Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase
      (ESBL)-producing bacteria, and multidrug-resistant Pseudomonas aeruginosa (MDRP)
      were 107 (8% of total bacterial tests performed), 51 (4%), and 4 (0.3%),
      respectively. Multivariate analyses of ABHS and tazobactam/piperacillin
      consumption showed a significant negative association with the MRSA isolation
      rate (adjusted R2 = 0.87). These findings suggest that hand hygiene is more
      important than antibiotic consumption in small to medium-sized hospitals.

PMID- 30217735
TI  - MicroRNA-96 is responsible for sevoflurane-induced cognitive dysfunction in
      neonatal rats via inhibiting IGF1R.
AB  - Sevoflurane is an experimental potent yet volatile anesthesia agent characterized
      by a low blood/gas partition coefficient. However, exposure to sevoflurane in
      neonatal mice has been speculated to result in learning deficits and abnormal
      social behavior. The aim of the present study was to investigate the relationship
      between sevoflurane and miR-96, in an attempt to identify the means by which it
      mediates IGF1R to influence the cognitive dysfunction (CD) in neonatal rats.
      Relationship between differentially expressed miRNAs and sevoflurane
      concentration was identified. The potential underlying regulatory mechanisms
      involved with sevoflurane were investigated through the administration of varying
      concentrations of the agent (1%, 2% and 4%), combined with miR-96 mimic or an
      inhibitor. A target prediction program was utilized, while the luciferase
      activity was determined in order to verify whether miR-96 targets IGF1R. The mRNA
      and protein levels of IGF1R, Bcl-2, Bax, and caspase-3 were measured followed by
      the determination of hippocampal neuron apoptosis. Learning and memory
      performance was assessed using the Morris water maze (MWM) test and step-down
      test. The obtained results highlighted a positive correlation between miR-96 and
      the concentration of sevoflurane, while miR-96 was confirmed to negatively target
      IGF1R. Our analyses indicated that 4% sevoflurane had a significantly stronger
      effect on reducing the levels of IGF1R and Bcl-2, while elevating the levels of
      miR-96, Bax and caspase-3 more so than that of 1% or 2% sevoflurane, which
      resulted in increased hippocampal neuron apoptosis but diminished the learning
      and memory performance of the rats. The addition of miR-96 mimic was demonstrated
      to exacerbate the influence of sevoflurane on hippocampal neurons as well as the
      cognitive function of the rats. The key findings of our study highlighted the
      role of miR-96 in the potential mechanism of sevoflurane anesthesia-induced CD in
      neonatal rats through the downregulation of IGF1R.

PMID- 30217736
TI  - Improving access to essential tests for infectious diseases.
AB  - Recently, WHO published the first ever Essential Diagnostics List (EDL), which
      includes 113 tests, including tests for HIV, TB, malaria, hepatitis B and C,
      human papillomavirus (HPV) and syphilis. The EDL is a welcome first step in
      ensuring that diagnostics are a key part of all health systems. The impact of the
      list, however, will depend greatly on how countries adopt and implement the EDL.

PMID- 30217737
TI  - Pictures in health information and their pitfalls: Focus group study and
      systematic review.
AB  - BACKGROUND: Health information often includes different categories of pictures.
      This study comprises: A) exploration of the perception of photos presented in a
      brochure on the prevention of osteoporosis and B) a systematic review on the
      effects of pictures in health information. METHODS: A) We conducted four focus
      groups. Participants with heterogeneous cultural and educational background were
      included. The interviews were subjected to qualitative content analysis. B) We
      searched PubMed, CENTRAL, PSYNDEX, PsycINFO, CINAHL, Campbell Collaboration and
      DIMDI. Randomized controlled trials (RCTs) on predefined cognitive and affective
      outcomes were included. Two independent reviewers extracted data and assessed the
      quality of evidence. Descriptive data synthesis was conducted. RESULTS: A) Within
      the focus groups comprising 37 participants, four generic categories were
      identified: comprehension, perception, congruence between photos and content, and
      alternatives. Identification with portrait photos and the connection between
      photos and text were important to participants. B) In total, 13 RCTs were
      included. Quality of evidence was moderate. Types of pictures and their intention
      varied between studies. Cartoons enhanced comprehension, satisfaction and
      readability. Photos did not improve cognitive or affective outcomes. Effects of
      anatomical pictures, pictographs, and drawings were ambiguous. CONCLUSION: The
      overall effect of using pictures in health information remains unclear. The type
      of pictures and readers' characteristics may influence both perception and
      interpretation. Type, amount, and intention of the pictures should be considered
      carefully.

PMID- 30217738
TI  - Searching for neural and behavioral parameters that predict anti-aggressive
      effects of chronic SSRI treatment in rats.
AB  - RATIONALE: Only a subset of impulsive aggressive patients benefits from selective
      serotonin reuptake inhibitor (SSRI) treatment, confirming contradictory results
      about the association between serotonin (5-hydroxytryptamine, 5-HT) and
      aggression. This shows the need to define behavioral characteristics within this
      subgroup to move towards individualized pharmacological treatment of impulsive
      aggression. METHODS: Here we submitted an outbred strain of Long Evans rats to a
      crossover design treatment regimen with the SSRI citalopram, to test its anti
      aggressive effect. Behavioral characteristics were baseline aggression, anxiety
      parameters as measured in the elevated plus maze and open field and cue
      responsivity as indicated by sign vs. goal tracking behavior. 5-HT1A receptor
      densities as measured by ex vivo [18F]MPPF binding were determined in the dorsal
      raphe nucleus, dentate gyrus, orbitofrontal cortex, infralimbic cortex and
      prelimbic cortex, because of the receptors' involvement in the therapeutic delay
      of SSRIs and aggression. RESULTS: We found statistically significant increased
      variance in aggressive behavior after citalopram treatment. However, none of the
      selected parameters predicted the citalopram treatment effect. CONCLUSION: Since
      aggression after citalopram treatment decreased in a subgroup of animals and
      increased in the other, future research should focus on other possible predictors
      to support treatment strategies in aggressive patients.

PMID- 30217739
TI  - Light-enhanced VEGF121/rGel: A tumor targeted modality with vascular and immune
      mediated efficacy.
AB  - Interactions between stromal cells and tumor cells pay a major role in cancer
      growth and progression. This is reflected in the composition of anticancer drugs
      which includes compounds directed towards the immune system and tumor-vasculature
      in addition to drugs aimed at the cancer cells themselves. Drug-based treatment
      regimens are currently designed to include compounds targeting the tumor stroma
      in addition to the cancer cells. Treatment limiting adverse effects remains,
      however, one of the major challenges for drug-based therapy and novel tolerable
      treatment modalities with diverse high efficacy on both tumor cells and stroma is
      therefore of high interest. It was hypothesized that the vascular targeted fusion
      toxin VEGF121/rGel in combination with the intracellular drug delivery technology
      photochemical internalization (PCI) stimulate direct cancer parenchymal cell
      death in addition to inhibition of tumor perfusion, and that an immune mediated
      response is relevant for treatment outcome. The aim of the present study was
      therefore to elucidate the anticancer mechanisms of VEGF121/rGel-PCI. In contrast
      to VEGF121/rGel monotherapy, VEGF121/rGel-PCI was found to mediate its effect
      through VEGFR1 and VEGFR2, and a targeted treatment effect was shown on two
      VEGFR1 expressing cancer cell lines. A cancer parenchymal treatment effect was
      further indicated on H&E stains of CT26-CL25 and 4 T1 tumors. VEGF121/rGel-PCI
      was shown, by dynamic contrast enhanced MRI, to induce a sustained inhibition of
      tumor perfusion in both tumor models. A 50% complete remission (CR) of CT26.CL25
      colon carcinoma allografts was found in immunocompetent mice while no CR was
      detected in CT26.CL25 bearing athymic mice. In conclusion, the present report
      indicate VEGF121/rGel -PCI as a treatment modality with multimodal tumor targeted
      efficacy that should be further developed towards clinical utilization.

PMID- 30217740
TI  - Wide-Area Transepithelial Sampling in Barrett's Esophagus: Ready for Primetime?

PMID- 30217741
TI  - The "I" in Depression: How Feeding the Immune System Can Lead to Behavioral
      Changes in Inflammatory Conditions.

PMID- 30217743
TI  - Whole Exome Sequencing Leading to Novel Therapeutic Discovery.

PMID- 30217742
TI  - Identification of Genes Associated With Hirschsprung Disease, Based on Whole
      Genome Sequence Analysis, and Potential Effects on Enteric Nervous System
      Development.
AB  - BACKGROUND & AIMS: Hirschsprung disease, or congenital aganglionosis, is believed
      to be oligogenic-that is, caused by multiple genetic factors. We performed whole
      genome sequence analyses of patients with Hirschsprung disease to identify
      genetic factors that contribute to disease development and analyzed the
      functional effects of these variants. METHODS: We performed whole-genome sequence
      analyses of 443 patients with short-segment disease, recruited from hospitals in
      China and Vietnam, and 493 ethnically matched individuals without Hirschsprung
      disease (controls). We performed genome-wide association analyses and gene-based
      rare-variant burden tests to identify rare and common disease-associated variants
      and study their interactions. We obtained induced pluripotent stem cell (iPSC)
      lines from 4 patients with Hirschsprung disease and 2 control individuals, and we
      used these to generate enteric neural crest cells for transcriptomic analyses. We
      assessed the neuronal lineage differentiation capability of iPSC-derived enteric
      neural crest cells using an in vitro differentiation assay. RESULTS: We
      identified 4 susceptibility loci, including 1 in the phospholipase D1 gene (PLD1)
      (P = 7.4 * 10-7). The patients had a significant excess of rare protein-altering
      variants in genes previously associated with Hirschsprung disease and in the beta
      secretase 2 gene (BACE2) (P = 2.9 * 10-6). The epistatic effects of common and
      rare variants across these loci provided a sensitized background that increased
      risk for the disease. In studies of the iPSCs, we observed common and distinct
      pathways associated with variants in RET that affect risk. In functional assays,
      we found variants in BACE2 to protect enteric neurons from apoptosis. We propose
      that alterations in BACE1 signaling via amyloid beta precursor protein and BACE2
      contribute to pathogenesis of Hirschsprung disease. CONCLUSIONS: In whole-genome
      sequence analyses of patients with Hirschsprung disease, we identified rare and
      common variants associated with disease risk. Using iPSC cells, we discovered
      some functional effects of these variants.

PMID- 30217744
TI  - Prostate Artery Embolization in Patients with Prostate Volumes of 80 mL or More:
      A Single-Institution Retrospective Experience of 93 Patients.
AB  - PURPOSE: To evaluate the safety and efficacy of prostate artery embolization
      (PAE) for the treatment of benign prostatic hyperplasia for prostates >= 80 mL.
      PATIENTS AND METHODS: A retrospective review was conducted of 93 patients with
      prostate volumes (PVs) >= 80 mL treated with PAE from April 2014 through October
      2017. Mean patient age was 68.5 years (range 52-88) and mean age-adjusted
      Charlson comorbidity index was 3.2 (range 1-8). Exclusion criteria included
      history of biopsy-proven prostate cancer or catheter dependency. Clinical and
      urodynamic outcomes were reviewed at 1, 3, 6, and 12 months. Adverse events were
      graded according to the Clavien-Dindo classification. RESULTS: Mean PV decreased
      significantly from 141.7 mL to 98.1 mL at 3 months (P < .01) and 82.2 mL at 12
      months (P < .01). Significant improvements were seen in 3- and 12-month mean
      International Prostate Symptom Scores (IPSS) (22.3 vs 7.1 and 7.3, respectively;
      P < .01 for both), quality of life (QOL) (4.4 vs 1.2 and 1.3; P < .01 for both),
      and postvoid residual volume (196.7mL vs 92.1 and 61.2 mL; P < .01 and P < .01,
      respectively). Significant improvement was also seen in 3-month mean maximum
      urinary flow: 7.7 mL/s vs 12.8 mL/s (P < .01). One grade II complication of
      stroke occurred; all other complications were self-limited and grade I.
      CONCLUSIONS: PAE achieved a clinically and statistically significant improvement
      in symptom burden and secondary outcome measures in patients with PVs >= 80 mL.
      PAE may be an alternate treatment for patients for whom conventional surgical
      options are limited or associated with significant morbidity.

PMID- 30217745
TI  - Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor
      Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere
      Radioembolization in Hepatocellular Carcinoma.
AB  - PURPOSE: To identify predictive factors of tumor response, progression-free
      survival (PFS), overall survival (OS), and toxicity using three-dimensional (3D)
      voxel-based dosimetry in patients with intermediate and advanced stage
      hepatocellular carcinoma (HCC) treated by yttrium-90 (90Y) resin microspheres
      radioembolization (RE). MATERIALS AND METHODS: From February 2012 to December
      2015, 45 90Y resin microspheres RE procedures were performed for HCC (Barcelona
      Clinic Liver Cancer stage B/C; n = 15/30). Area under the dose-volume histograms
      (AUDVHs) were calculated from 3D voxel-based dosimetry to measure 90Y dose
      deposition. Factors associated with tumor control (ie, complete/partial response
      or stable disease on Modified Response Evaluation Criteria in Solid Tumors) at 6
      months were investigated. PFS and OS analyses were performed (Kaplan-Meier).
      Toxicity was assessed by occurrence of radioembolization-induced liver disease
      (REILD). RESULTS: Tumor control rate was 40.5% (17/42). Complete tumor targeting
      (odds ratio = 36.97; 95% confidence interval, 1.83-747; P < .001) and AUDVHtumor
      (odds ratio = 1.027; 95% confidence interval, 1.002-1.071; P = .033)
      independently predicted tumor control. AUDVHtumor >= 61 Gy predicted tumor
      control with 76.5% sensitivity and 75% specificity. PFS and OS in patients with
      incomplete tumor targeting were significantly shorter than in patients with
      complete tumor targeting (median PFS, 2.7 months [range, 0.8-4.6 months] vs 7.9
      months [range, 2.1-39.5 months], P < .001; median OS, 4.5 months [range, 1.4-23
      months] vs 19.2 months [range, 2.1-46.9 months], P < .001). Patients with
      incomplete tumor targeting and AUDVHtumor < 61 Gy, incomplete tumor targeting and
      AUDVHtumor > 61 Gy, complete tumor targeting and AUDVHtumor < 61 Gy, and
      AUDVHtumor > 61 Gy had median PFS of 2.7, 1.8, 6.3, and 12.1 months (P < .001).
      REILD (n = 4; 9.5%) was associated with higher dose delivered to normal liver (P
      = .04). CONCLUSIONS: Complete tumor targeting and 90Y dose to tumor are
      independent factors associated with tumor control and clinical outcomes.

PMID- 30217746
TI  - Intranodal Glue Embolization for the Management of Postsurgical Groin Lymphocele
      and Lymphorrhea.
AB  - This report describes intranodal lymphatic embolization for treatment of groin
      lymphatic leaks following surgery or percutaneous vascular interventions. In 10
      consecutive patients with groin lymphatic leak between 2015 and 2017,
      lymphangiography with embolization was performed by intranodal injection with
      dilute N-butyl cyanoacrylate (NBCA). Mean volume of dilute NBCA (1:3 with
      ethiodized oil) injected was 1 mL. Clinical success rate was 80%. Median time to
      resolution was 7 days. Intranodal lymphatic embolization for treatment of groin
      lymphatic leaks is a safe and effective treatment alternative to surgery
      resulting in a rapid time to resolution.

PMID- 30217747
TI  - Dual-Energy CT-Derived Volumetric Iodine Concentration for the Assessment of
      Therapeutic Response after Microwave Ablation in a Rabbit Model with Intrahepatic
      VX2 Tumor.
AB  - PURPOSE: To evaluate whether changes in volumetric iodine concentration (VIC)
      could serve as a suitable predictor of therapeutic response to microwave (MW)
      ablation in a rabbit intrahepatic VX2 tumor model. MATERIALS AND METHODS: Sixteen
      intrahepatic VX2 tumors were transplanted in 8 New Zealand White rabbits treated
      with MW ablation. Contrast-enhanced dual-energy CT scans were obtained at
      baseline and follow-up. Therapeutic response assessment by modified Response
      Evaluation Criteria In Solid Tumors (mRECIST), Choi criteria, and VIC changes was
      performed. An intraclass correlation coefficient (ICC) was used to characterize
      consistency of assessment results among the criteria used. Technical success was
      evaluated with explant pathologic findings as a reference. Correlations between
      technical success and variations in diameter, CT density, and VIC were analyzed.
      RESULTS: Disease control was observed in 4, 8, and 10 of the 16 tumors per
      mRECIST, Choi criteria, and VIC changes, respectively. VIC exhibited strong
      consistency (ICC = 0.807, P < .0001) with Choi criteria. According to explant
      pathology, technical success was achieved in 10 of the 16 tumors. There was a
      moderate correlation between VIC changes and technical success (r = 0.532, P =
      .034), and no correlation was found between technical success and variations in
      diameter or CT density. CONCLUSIONS: Compared with mRECIST and Choi criteria,
      dual-energy CT-derived VIC allowed for better prediction of therapeutic response
      after MW ablation and could provide a potential imaging biomarker of tumor
      response to MW ablation in patients with hepatocellular carcinoma.

PMID- 30217748
TI  - Extraluminal Recanalization of Bile Duct Anastomosis Obstruction after Liver
      Transplantation.
AB  - This report describes extraluminal recanalization of bile duct anastomosis
      obstruction after living donor liver transplantation. The procedure was performed
      in 5 patients in whom negotiation of the biliary anastomotic obstruction by
      retrograde endoscopic approach and percutaneous intraluminal recanalization had
      failed. Extraluminal puncture from the donor bile duct to the recipient side bile
      duct was made with the stiff back end of a 0.035-inch hydrophilic guide wire.
      After recanalization, a percutaneous transhepatic biliary drainage catheter was
      placed through the created tract. In all 5 patients, extraluminal recanalization
      was achieved without major complication, and endoscopic plastic stents were
      subsequently placed along the tract.

PMID- 30217749
TI  - Comparison of Conventional and Cone-Beam CT for Monitoring and Assessing
      Pulmonary Microwave Ablation in a Porcine Model.
AB  - PURPOSE: To compare cone-beam computed tomography (CT) with conventional CT for
      assessing the growth and postprocedural appearance of pulmonary microwave
      ablation zones. MATERIALS AND METHODS: A total of 17 microwave ablations were
      performed in porcine lung in vivo by applying 65 W for 5 minutes through a single
      17-gauge antenna. Either CT (n = 8) or CBCT (n = 9) was used for guidance and
      ablation zone monitoring at 1-minute intervals. Postprocedural noncontrast images
      were acquired with both modalities. Three independent readers measured the
      length, width, cross-sectional area, and circularity of the ablation zones on
      gross tissue samples and CT and cone-beam CT images. The measurements were
      compared via linear mixed-effects models for postprocedural appearance and with a
      polynomial mixed effects model for ablation zone growth curves. RESULTS: On
      postprocedural images, the differences between cone-beam CT and CT in mean length
      (3.84 vs 3.86 cm; Delta = -0.02; P = .70), width (2.61 vs 2.56 cm; Delta = 0.06;
      P = .46), area (7.84 vs 7.65 cm2; Delta = 0.19; P = .35), and circularity (0.85
      vs 0.85; Delta = 0.01; P = .62) were not statistically significant after
      accounting for intersubject and interrater variability. Also, there was no
      significant difference between CT and cone-beam CT growth curves of the ablation
      zones during monitoring in terms of length (pInt. = 1.00; pLin.Slope = 0.52;
      pQuad.Slope = 0.69); width (pInt. = 0.83; pLin.Slope = 0.98; pQuad.Slope = 0.79),
      area (pInt. = 0.47; pLin.Slope = 0.27; pQuad.Slope = 0.57), or circularity (pInt.
      = 0.54; pLin.Slope = 0.74; pQuad.Slope = 0.80). Both CT and cone-beam CT
      overestimated gross pathologic observations of ablation length, width, and area
      (P < .001 for all). CONCLUSIONS: Cone-beam CT was similar to conventional CT when
      assessing the growth, final size, and shape of pulmonary microwave ablation zones
      and may be useful for monitoring and evaluating microwave ablations in the lung.

PMID- 30217750
TI  - Elevated plasma cartilage oligomeric matrix protein (COMP) level are associated
      with the progression of non-traumatic osteonecrosis of femoral head.

PMID- 30217751
TI  - Quantification of methylcitrate in dried urine spots by liquid chromatography
      tandem mass spectrometry for the diagnosis of propionic and methylmalonic
      acidemias.
AB  - Accumulation of methylcitrate is a biochemical hallmark of inborn errors of
      propionate metabolism, a group of disorders that include propionic acidemia,
      methylmalonic aciduria and cobalamin defects. In clinical laboratories, this
      analyte is measured without quantification by gas chromatography mass
      spectrometry as part of urine organic acids. Here we describe a simple, sensitive
      and specific method to quantify methylcitrate in dried urine spots by liquid
      chromatography tandem mass spectrometry. Methylcitrate is extracted and
      derivatized with 4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-(2
      aminoethylamino)-2,1,3-benzoxadiazole in a single step. A derivatization mixture
      was added to 3.2 mm disc of dried urine spots, incubated at 65  degrees C for 45
      min and 4 MUl of the reaction mixture were analyzed. Separation was achieved on
      C18 column with methylcitrate eluting at 3.8 min. Intraday and interday
      imprecision (n = 17) were <=20.9%. The method was applied on dried urine spots
      from established patients and controls. In controls (n = 135), methylcitrate
      reference interval of 0.4-3.4 mmol/mol creatinine. In patients, methylcitrate
      ranged between 8.3 and 591 mmol/mol creatinine. Quantification of methylcitrate
      provides important diagnostic clues for propionic acidemia, methylmalonic
      aciduria and cobalamin disorders. The potential utilization of methylcitrate as
      monitoring biomarker of patients under treatment and whether it correlates with
      the clinical status has yet to be established.

PMID- 30217752
TI  - HAND2 loss-of-function mutation causes familial dilated cardiomyopathy.
AB  - As two members of the basic helix-loop-helix family of transcription factors,
      HAND1 and HAND2 are both required for the embryonic cardiogenesis and postnatal
      ventricular structural remodeling. Recently a HAND1 mutation has been reported to
      cause dilated cardiomyopathy (DCM). However, the association of a HAND2 mutation
      with DCM is still to be ascertained. In this research, the coding regions and
      splicing junction sites of the HAND2 gene were sequenced in 206 unrelated
      patients affected with idiopathic DCM, and a new heterozygous HAND2 mutation,
      NM_021973.2: c.199G > T; p.(Glu67*), was discovered in an index patient with DCM.
      The nonsense mutation was absent in 300 unrelated, ethnically-matched healthy
      persons. Genetic scan of the mutation carrier's family members revealed that the
      genetic mutation co-segregated with DCM, which was transmitted in an autosomal
      dominant fashion, with complete penetrance. Functional deciphers unveiled that
      the mutant HAND2 protein had no transcriptional activity. In addition, the
      mutation abrogated the synergistic transcriptional activation between HAND2 and
      GATA4 or between HAND2 and NKX2.5, two other cardiac transcription factors that
      have been implicated in DCM. These research findings firstly suggest HAND2 as a
      novel gene predisposing to DCM in humans, which adds novel insight to the
      molecular pathogenesis of DCM, implying potential implications in the design of
      personized preventive and therapeutic strategies against DCM.

PMID- 30217753
TI  - Clinical and genetic heterogeneity in Melkersson-Rosenthal Syndrome.
AB  - Melkersson Rosenthal syndromes (MRS) is a rare autosomal dominantly inherited
      neurocutaneous syndrome characterised by a triad of facial (seventh cranial)
      nerve palsy, recurrent orofacial swelling and fissuring of the tongue. A recent
      report implicated a heterozygous missense variant in SLC27A1 (FATP1) as the cause
      of this condition in members of an affected Chinese family. We undertook Sanger
      sequencing of this gene in 14 affected unrelated individuals affected by MRS. We
      did not detect any putative pathogenic variants. Our data indicates that there is
      both clinical and genetic heterogeneity in this condition and that the causative
      gene remains to be identified for the majority of cases.

PMID- 30217754
TI  - Hyperphosphatasia with mental retardation syndrome type 4 In two siblings
      expanding the phenotypic and mutational spectrum.
AB  - Hyperphosphatasia with mental retardation syndrome (HPMRS) (OMIM # 239300), is an
      autosomal recessive disease with phenotypic variability, ranging from mild
      nonsyndromic intellectual disability to syndromic form with severe intellectual
      disability, seizures, elevated alkaline phosphatase, brachytelephalangy and
      facial dysmorphism, Six subgroups of HPMRS were defined in which pathogenic
      mutations affect genes involved in either synthesis or remodeling of the anchor
      proteins. Among these, PGAP3 mutations are associated with HPMRS type 4. We
      report two siblings with a novel homozygous variant in PGAP3 expanding both the
      phenotypic findings and the mutational spectrum of HPMRS type 4. Developmental
      delay, hypotonia, facial dysmorphism were the consistent findings with HPMRS in
      our patients. Large anterior fontanel size, gum hypertrophy, pes equinovarus,
      concentric ventricle hypertrophy, frontoparietal atrophy and dysphagia were the
      findings of our patients that have been reported for the first time in this
      syndrome. Although there is an extensive list of differential diagnoses in
      patients with developmental delay and hypotonia, the recognizable pattern of
      facial features, parental consanguinity and mild to moderate serum ALP elevation
      should be sufficiently suggestive of HPMRS type 4.

PMID- 30217755
TI  - Dorsal Cochlear Nucleus Fusiform-cell Plasticity is Altered in Salicylate-induced
      Tinnitus.
AB  - Following noise overexposure and tinnitus-induction, fusiform cells of the dorsal
      cochlear nucleus (DCN) show increased spontaneous firing rates (SFR), increased
      spontaneous synchrony and altered stimulus-timing-dependent plasticity (StDP),
      which correlate with behavioral measures of tinnitus. Sodium salicylate, the
      active ingredient in aspirin, which is commonly used to induce tinnitus,
      increases SFR and activates NMDA receptors in the ascending auditory pathway.
      NMDA receptor activation is required for StDP in many brain regions, including
      the DCN. Blocking NMDA receptors can alter StDP timing rules and decrease
      synchrony in DCN fusiform cells. Thus, systemic activation of NMDA receptors with
      sodium salicylate should elicit pathological changes to StDP, thereby increasing
      SFR and synchrony and induce tinnitus. Herein, we examined the action of
      salicylate in tinnitus generation in guinea pigs in vivo by measuring tinnitus
      using two behavioral measures and recording single-unit responses from DCN
      fusiform cells pre- and post-salicylate administration in the same animals.
      First, we show that animals administered salicylate show evidence of tinnitus
      using both behavioral paradigms, cross-validating the tests. Second, fusiform
      cells in animals with tinnitus showed increased SFR, synchrony and altered StDP
      timing rules, like animals with noise-induced tinnitus. These findings suggest
      that alterations to fusiform-cell plasticity are an essential component of
      tinnitus, regardless of induction technique.

PMID- 30217756
TI  - Hemispheric language lateralization in presurgical patients with temporal lobe
      epilepsy: Improving the retest reliability of functional transcranial Doppler
      sonography.
AB  - Since its introduction, functional transcranial Doppler sonography (fTCD) has
      been extensively applied in research and clinical settings and has now become
      part of the routine presurgical work-up of patients with epilepsy. Because of its
      importance in planning neurosurgical interventions and predicting possible
      cognitive risks, the reproducibility of fTCD in determining hemispheric language
      lateralization (HLL) has to be ensured. In the present study, fTCD was performed
      twice in 33 initially lateralized patients with temporal lobe epilepsy (TLE) as
      part of their presurgical work-up, using a standard word generation paradigm.
      Initially, the standard analysis, including only the statistical examination of
      fTCD data, was applied, and a rather poor retest reliability of r = 0.41 was
      obtained (p = 0.017). Because of doubts concerning appropriate task performance
      in some patients, subsequently, a two-step data analysis was introduced,
      including an additional qualitative evaluation of fTCD data regarding (1)
      instruction-compliant task performance, (2) sufficient quality of the baseline
      phase, and (3) adequate increase in cerebral blood flow velocity (CBFV) during
      the activation phase. Attributable to a more valid interpretation of fTCD data
      after the application of the qualitative step, the reproducibility of HLL
      significantly improved (p = 0.007) to a high retest reliability of r = 0.84 (p <
      0.000). In clinical settings, psychological and situational factors seem to
      strongly influence the reproducibility of fTCD determining HLL. Accordingly, we
      highly recommend the complementation of the standard statistical examination of
      fTCD data by an additional qualitative evaluation (two-step data analysis), as
      this extra security is particularly desirable because of its direct implications
      for the further evaluation of neurosurgical interventions. This article is part
      of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and
      Beyond".

PMID- 30217757
TI  - Sequence analysis of alpha-(1, 2)-fucosyltransferase gene in nine Chinese
      individuals with Para-Bombay phenotype.
AB  - BACKGROUND: To analyze the sequence of alpha-(1, 2)-fucosyltransferase gene
      (FUT1) in nine individuals with Para-Bombay phenotype. METHODS: Para-Bombay
      phenotype was defined according to the serologic characteristics and ABO
      genotypes. The full coding region of FUT1 was amplified, genotype and haplotype
      were analyzed by direct and TOPO cloning sequencing which was used to
      discriminate heterozygous mutations of FUT1. RESULTS: These nine individuals were
      identified as three Para-Bombay A (Ah), six Para-Bombay B (Bh) according to
      serologic characteristics and ABO genotypes. According to the direct and cloning
      sequencing results of the full coding region of FUT1, five genotypes and five
      haplotypes were found in these nine individuals. CONCLUSION: Two complex
      mutations of FUT1 were discovered, which were h1h547 - 552delAG + 814A > G (c.547
      - 552delAG, p.Arg183Argfs * 86; c.547 - 552delAG, p.Arg183Argfs * 86 + c.814A >
      G, p.lle272Val) and h755G > Ch547 - 552delAG + 755G > C (c.755G > C,
      p.Arg183Argfs * 86; c.547 - 548delAG, p.Arg183Argfs * 86 + c.755G > C,
      p.Arg253Pro), the genotype of h755G > Ch547 - 552delAG + 755G > C was reported
      for the first time, and three kinds of known genotype (h1h1, h3h3, h1h3) were
      found also in these nine Chinese individuals with Para-Bombay phenotype in the
      present study. In this way, the FUT1 mutation showed a distinct geographic and
      ethnic range.

PMID- 30217758
TI  - Novel KDM5B splice variants identified in patients with developmental disorders:
      Functional consequences.
AB  - Histone lysine methylation influences processes such as gene expression and DNA
      repair. Thirty Jumonji C (JmjC) domain-containing proteins have been identified
      and phylogenetically clustered into seven subfamilies. Most JmjC domain
      containing proteins have been shown to possess histone demethylase activity
      toward specific histone methylation marks. One of these subfamilies, the KDM5
      family, is characterized by five conserved domains and includes four members.
      Interestingly, de novo loss-of-function and missense variants in KDM5B were
      identified in patients with intellectual disability (ID) and autism spectrum
      disorder (ASD) but also in unaffected individuals. Here, we report two novel de
      novo splice variants in the KDM5B gene in three patients with ID and ASD. The
      c.808 + 1G > A variant was identified in a boy with mild ID and autism traits and
      is associated with a significant reduced KDM5B mRNA expression without alteration
      of its H3K4me3 pattern. In contrast, the c.576 + 2T > C variant was found in
      twins with global delay in developmental milestones, poor language and ASD. This
      variant causes the production of an abnormal transcript which may produce an
      altered protein with the loss of the ARID1B domain with an increase in global
      gene H3K4me3. Our data reinforces the recent observation that the KDM5B
      haploinsufficiency is not a mechanism involved in intellectual disability and
      that KDM5B disorder associated with LOF variants is a recessive disorder.
      However, some variants may also cause gain of function, and need to be
      interpreted with caution, and functional studies should be performed to identify
      the molecular consequences of these different rare variants.

PMID- 30217759
TI  - Gene-gene interactions and associations of six hypertension related single
      nucleotide polymorphisms with obesity risk in a Chinese children population.
AB  - Obesity is a major risk for hypertension. However, the associations between
      hypertension susceptibility loci and the risk of obesity as well as the effects
      of gene-gene interactions are unclear, especially in the Chinese children
      population. Six single nucleotide polymorphisms (SNPs) (ATP2B1 rs17249754, CSK
      rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777, FGF5 rs16998073)
      were genotyped for 3503 Chinese children, aged 6-18 years. Of them, 758 obese
      cases and 2745 controls were identified based on the International Obesity Task
      Force age- and sex-specific BMI references. Among the six SNPs, three were
      associated with obesity risk (CSK rs1378942: odds ratio (OR) = 1.20, 95%
      confidence interval (CI) 1.01-1.43, P = 0.042; MTHFR rs1801133: OR = 1.19, 95% CI
      1.05-1.34, P = 0.006; FGF5 rs16998073: OR = 1.14, 95% CI 1.00-1.29, P = 0.047).
      The genetic risk score (GRS), based on these three SNPs (CSK rs1378942, MTHFR
      rs1801133, FGF5 rs16998073), showed a positive association with risk of obesity
      (OR = 1.18, 95% CI 1.09-1.28, P = 7.60 * 10-5). The same association signals were
      also detected in the subgroups of puberty and inactivity. In addition,
      interaction analyses among these loci implied a potential gene-gene interaction
      between MTHFR and FGF5. These findings show a significant association of
      hypertension susceptibility loci in Chinese children, suggesting a likely
      influence of genetic and environmental factors on the risk of obesity.

PMID- 30217760
TI  - Efficacy of the Nordic and the MSKCC chemotherapy protocols on the overall and
      progression-free survival in intracranial PCNSL.
AB  - BACKGROUND: To compare the Nordic and the Memorial Sloan-Kettering Cancer Center
      (MSKCC) chemotherapy protocols for Overall Survival (OS) and Progression-Free
      Survival (PFS) for intracranial primary CNS lymphoma (PCNSL). METHODS: A
      prospective database at Oslo University Hospital of PCNSL was reviewed over a 12
      year period (2003-2014). RESULTS: Overall, 79 patients with PCNSL were
      identified, of whom 57 received chemotherapy. MSKCC with Rituximab (RTX) was used
      in 18 patients (32%) who had median OS of 46.3 months [9.8-131.9] and median PFS
      of 34.6 months [6.4-131.9]. The Nordic protocol was used in 14 patients (25%) who
      had median OS of 30.9 months [2.7-106.3] and PFS of 14.3 months [0.0-106.3]. The
      MSKCC was used without RTX in 25 patients (44%) who had OS of 15.2 months [0.7
      136.5] and PFS of 12.0 months [0.0-117.0]. MSKCC with RTX had a significantly
      longer median OS (p < 0.05) compared to the other regimens in univariate
      analysis. In multivariate analysis, the only prognostic factor for OS and PFS of
      significance was deep brain involvement (p < 0.005). CONCLUSIONS: In univariate
      analysis, the MSKCC with RTX achieved significantly longer median OS compared to
      the Nordic protocol. However, in multivariate analysis, the only prognostic
      factor for survival of statistical significance was deep brain involvement.

PMID- 30217761
TI  - Clinical and microbiological features of bacteraemia with Gram-positive anaerobic
      cocci: a population-based retrospective study.
AB  - OBJECTIVES: Gram-positive, anaerobic cocci (GPAC) can cause infections in humans.
      Only a few cases of bacteraemia with GPAC have been reported. We describe the
      clinical and microbiological characteristics of GPAC bacteraemia. METHODS: A
      retrospective population-based study of GPAC bacteraemia 2012-2016 in southern
      Sweden was performed. GPAC were identified using matrix-associated laser
      desorption ionization time-of-flight mass spectrometry or 16S rRNA gene
      sequencing. Etests were used to determine antibiotic susceptibilities. Data on
      patient and infection characteristics, treatment, and outcome were collected from
      the medical records. RESULTS: A total of 226 episodes of GPAC bacteraemia in
      adults were studied; this corresponds to an annual incidence of 3.4 cases per
      100,000 persons per year. The bacteria identified were Anaerococcus spp. (n =
      43), Atopobium spp. (n = 7), Blautia spp. (n = 1), Finegoldia spp. (n = 15),
      Parvimonas spp. (n = 100), Peptoniphilus spp. (n = 52), Peptostreptococcus spp.
      (n = 2), and Ruminococcus spp. (n = 9) of which 200 isolates were identified to
      the species level. Resistance to imipenem and piperacillin was not identified,
      whereas resistance among the 229 isolates to penicillin was detected in four, to
      metronidazole in six, and clindamycin in 16 isolates. The median age of patients
      was 73 years (55-83, IQR), 57% were male and comorbidities were common. Fifty-one
      per cent of infections were polymicrobial. In 60% of cases a focus of infection
      was identified. Forty per cent of patients had either organ dysfunction or shock.
      The 30-day mortality was 11%, and nosocomial infections were over-represented
      among the deceased. CONCLUSIONS: GPAC bacteraemia is much more common than
      previously reported. GPAC-bacteraemia is a condition with significant mortality
      mainly affecting elderly persons with comorbidities.

PMID- 30217762
TI  - Corrigendum to 'Assessing prediction accuracy for outcomes of ventilator
      associated events and infections in critically ill children: a prospective cohort
      study' [Clinical Microbiology and Infection, Volume 24, Issue 7 (July 2018) Pages
      732-737].

PMID- 30217763
TI  - Incidence and Outcomes of Delayed Targeted Therapy After Cytoreductive
      Nephrectomy for Metastatic Renal-Cell Carcinoma: A Nationwide Cancer Registry
      Study.
AB  - BACKGROUND: The optimal timing of targeted therapy (TT) initiation for metastatic
      renal-cell carcinoma (mRCC) is not clear. We used a nationwide cancer registry to
      determine clinical and social factors associated with delayed TT and to evaluate
      the association of a delayed approach with overall survival (OS). PATIENTS AND
      METHODS: We performed a retrospective observational study utilizing the National
      Cancer Data Base from 2006 to 2012 for patients diagnosed with mRCC (clear-cell
      histology) treated with cytoreductive nephrectomy and TT. Time to initiation of
      TT was defined as early (within 2 months), moderately delayed (2-4 months),
      delayed (4-6 months), and late (> 6 months). RESULTS: Of the 2716 patients
      included in the analysis, the median (interquartile range) time from diagnosis to
      initiation of TT was 2.1 (1.3-3.23) months. A total of 1255 patients (46.2%) had
      early TT, 1072 patients (39.5%) had moderately delayed TT, 284 patients (10.5%)
      had delayed TT, and 105 patients (3.9%) had late TT. Delay in TT initiation was
      not independently associated with OS in multivariable analysis. The time interval
      from diagnosis to TT initiation was not correlated with time from initiation of
      TT to death (r = 0.04, P = .08). CONCLUSION: We found that delayed initiation of
      TT was not an independent predictor of worse OS. Although this study is subject
      to limitations of observation study design and selection bias, the results are
      consistent with the notion that in carefully selected patients, outcomes might
      not be compromised with initial observation.

PMID- 30217764
TI  - Impact of Neoadjuvant Chemotherapy on Pathologic Response in Patients With Upper
      Tract Urothelial Carcinoma Undergoing Extirpative Surgery.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) has been increasingly adopted in the
      management of high-grade upper tract urothelial carcinoma (UTUC), largely
      extrapolating from level I evidence in urothelial carcinoma of the bladder.
      Studies examining pathologic outcomes in patients with UTUC receiving NAC are
      mostly limited to retrospective, single-center studies with limited sample size,
      with results of a phase II trial recently presented. Hypothesizing that NAC is
      associated with improved pathologic response (PR), we compared pathologic
      outcomes in patients with high-grade UTUC who did and did not receive NAC before
      extirpative surgery. PATIENTS AND METHODS: A total of 6174 patients with
      nonmetastatic, high-grade UTUC who underwent extirpative surgery from 2006 to
      2014 were identified from the National Cancer Database. Patients were stratified
      by NAC status. PR was defined as pathologic stage less than clinical stage.
      Univariate and multivariable logistic regression analysis was employed to
      identify predictors of PR. RESULTS: Two hundred sixty (4.2%) patients received
      NAC. A higher incidence of PR was observed in patients receiving NAC (25.2% vs.
      1.8%; P < .001), with complete PR observed in 6.1% of patients receiving NAC and
      0.4% of patients undergoing surgery alone. NAC (odds ratio [OR], 19.8; 95%
      confidence interval [CI], 11.8-33.5), nonwhite race (OR, 3.2; 95% CI, 1.7-6.3),
      and ureteral tumor location (OR, 1.6; 95% CI, 1.02-2.6) were independently
      associated with PR. CONCLUSIONS: Examining a large national cancer registry, we
      observed a higher incidence of PR in patients with UTUC receiving NAC, validating
      findings of prior studies. Our findings support consideration of NAC in high
      grade UTUC. Prospective trials will better define the impact of NAC on pathologic
      and survival outcomes.

PMID- 30217765
TI  - Patient-derived induced pluripotent stem cells for modelling genetic retinal
      dystrophies.
AB  - The human retina is a highly complex tissue that makes up an integral part of our
      central nervous system. It is astonishing that our retina works seamlessly to
      provide one of our most critical senses, and it is equally devastating when a
      disease destroys a portion of the retina and robs people of their vision. After
      decades of research, scientists are beginning to understand retinal cells in a
      way that can benefit the millions of individuals suffering from inherited
      blindness. This understanding has come about in part with the ability to culture
      human embryonic stem cells and the innovation of induced pluripotent stem cells,
      which can be cultured from patients and used to model their disease. In this
      review, we highlight the successes of specific disease modelling studies and
      resulting molecular discoveries. The greatest strides in cellular modelling have
      come from mutations in genes with established and well-understood cellular
      functions in the context of the retina. We believe that the future of cellular
      modelling depends on emphasising reproducible production of retinal cell types,
      demonstrating functional rescue using site-specific programmable nucleases, and
      shifting towards unbiased screening using next generation sequencing.

PMID- 30217766
TI  - Comparative study of the therapeutic effect of Doxorubicin and Resveratrol
      combination on 2D and 3D (spheroids) cell culture models.
AB  - The assessment of drug-combinations for pancreatic cancer treatment is usually
      performed in 2D cell cultures. In this study, the therapeutic effect and the
      synergistic potential of a particular drug-combination towards 2D and 3D cell
      cultures of pancreatic cancer were compared for the first time. Thus, the effect
      of Doxorubicin:Resveratrol (DOX:RES) combinations (at molar ratios ranging from
      5:1 to 1:5) in the viability of PANC-1 cells cultured as 2D monolayers and as 3D
      spheroids was analyzed. The results showed that the cells' viability was more
      affected when DOX:RES combinations containing higher contents of RES (1:2-1:5
      molar ratios) were used. This can be explained by the ability of RES to reduce
      the P-glycoprotein (P-gp)-mediated efflux of DOX. Further, it was also revealed
      that the synergic effect of this drug combination was different in 2D and in 3D
      cell cultures. In fact, despite of the 1:4 and 1:5 DOX:RES ratios being both
      synergistic for both types of PANC-1 cell cultures, their Combination Indexes
      (CI) in the monolayers were lower than those attained in spheroids. Overall, the
      obtained results revealed that the DOX:RES combination is promising for
      pancreatic cancer treatment and corroborate the emergent need to evaluate drug
      combinations in 3D cell cultures.

PMID- 30217767
TI  - Dry powder inhaler formulations of poorly water-soluble itraconazole: A balance
      between in-vitro dissolution and in-vivo distribution is necessary.
AB  - Formulating poorly water-soluble drug, itraconazole (ITZ), as dry powder inhaler
      (DPI) may be more effective for the treatment of invasive pulmonary Aspergillosis
      than intravenous injection and oral administration. It is necessary to improve
      the dissolution of ITZ because the alveolar lining fluid is limited and thus the
      dissolution of ITZ in the lung may be slow and incomplete. However, too fast
      dissolution may result in over-absorption into the circulation and thus
      insufficient distribution in the lung. The purpose of this study is to understand
      the relationship between in-vitro dissolution and in-vivo distribution of ITZ
      from DPI formulations. Two DPI formulations (F1 and F2) with identical
      compositions and similar aerodynamic behaviors were fabricated by hot melt
      extrusion and thus jet-milling. ITZ was formulated with mannitol as fine solid
      crystal suspension system to effectively improve its dissolution. In-vitro
      dissolution tests and in-vivo pharmacokinetic studies indicated that F1 released
      faster than F2 under both sink and non-sink conditions, but exhibited a lower
      lung retention and higher plasma absorption than F2. These results suggested that
      although dissolution enhancement of poorly water-soluble drugs in pulmonary
      delivery may be necessary to overcome problems such as local irritation and quick
      elimination by macrophages, it may have an impact on the distribution of the drug
      between the lung and the plasma. A balance between airway dissolution and
      systemic absorption should be taken into consideration when developing DPI
      formulations of poorly water-soluble ITZ.

PMID- 30217768
TI  - Polyvinylpyrrolidone affects thermal stability of drugs in solid dispersions.
AB  - The present study explores the hypothesis that a polymer can affect the thermal
      stability of a drug in solid polymer-drug dispersions. The hypothesis is tested
      in a systematic fashion by combining isoconversional kinetic analysis with
      thermogravimetric measurements on several solid dispersions. Experimental systems
      involve three drugs: indomethacin (IMC), felodipine (FD), and nifedipine (ND) and
      their solid dispersions with polyvinylpyrrolidone (PVP). It is found that PVP
      stabilizes IMC but destabilizes FD and ND. Isoconversional kinetic analysis
      provides insights into the origin of the observed effects. The enhanced thermal
      stability of IMC in the PVP matrix is associated with an increase in the
      activation energy of the respective degradation process. A detrimental effect of
      the PVP matrix on the stability of FD and ND has been linked to a decrease in the
      activation energy and an increase in the preexponential factor, respectively. The
      molecular underpinnings of the observed effects are discussed. It is concluded
      that the effects in question are of relevance for drug performance and need to be
      taken into account in preformulation studies.

PMID- 30217769
TI  - Prevention of corneal neovascularization by subconjunctival injection of
      avastin(r) loaded thermosensitive hydrogels in rabbit model.
AB  - The antibody avastin(r) (Ava) has been clinically to treat various intraocular
      neovascular diseases, but suffering from the rapid clearance and short shelf-life
      of Ava in the requirement of frequent administration. In the present study, we
      reports the sustained release of Ava from a thermosensitive hydrogel based on
      poly(ethylene glycol)-poly(E-caprolactone)-poly(ethylene glycol) (PECE) copolymer
      for the control of corneal neovascularization in rabbit model. Ava were
      physically mixed with PECE aqueous solution at 4  degrees C, and resulting Ava
      PECE solution showed a sol-gel transition at physiological temperature (37 
      degrees C). In vitro release study indicated that Ava-PECE hydrogel provided a
      sustained release of Ava up to 28 days and the drug release behavior could be
      finely modulated by the change of PECE concentration. A single subconjunctival
      injection of PECE hydrogel hardly caused the change of intraocular pressure and
      corneal endothelial morphology during the entire study period. Intraocular
      pharmacokinetic analysis suggested that the Ava-PECE hydrogel provided a
      relatively higher Ava concentration in cornea over Ava solution up to 14 days. In
      addition, anti-angiogenic effects of the Ava-PECE hydrogel in a suture-induced
      corneal neovascularization rabbit model indicated that the Ava-PECE hydrogel
      treatment exhibited superior anti-angiogenic efficacy over Ava solution treatment
      by decreasing the area ratio of neovascularization on 17 days. Overall, the
      proposed Ava-PECE hydrogel acting a sustained drug delivery system might be a
      promising vehicle for the treatment of corneal neovascularization.

PMID- 30217770
TI  - Can we predict treatment response in children with ADHD to a vitamin-mineral
      supplement? An investigation into pre-treatment nutrient serum levels, MTHFR
      status, clinical correlates and demographic variables.
AB  - BACKGROUND: Intent-to-treat analyses from a randomized controlled trial showed
      significant between-group differences favouring micronutrient treatment on the
      Clinical Global Impression-Improvement, but no group differences on clinician,
      parent and teacher ratings of overall ADHD symptoms. There was an advantage of
      micronutrients over placebo in improving overall function, emotional regulation,
      aggression, and reducing impairment as well as improving inattention based on
      clinician but not parent observation. No group differences were observed on
      hyperactive-impulsive symptoms. We investigated predictors of response defined by
      pre-treatment variables. METHOD: We conducted analyses of data from a clinical
      trial of children (7-12 years) with ADHD, whereby participants were randomized to
      receive micronutrients or placebo for 10 weeks followed by a 10 week open-label
      (OL) phase. We included only children who had been exposed to micronutrients for
      a full 10 week period and demonstrated satisfactory adherence, either in RCT
      phase (n = 40) or OL phase (those who received placebo during RCT phase; n = 31).
      Seven outcomes were examined: change in ADHD symptoms (clinician/parent), ADHD
      responder, overall responder, change in mood, change in functioning, and change
      in aggression. Demographic, developmental variables, current clinical and
      physical characteristics, MTHFR genotype at two common variants, and pre
      treatment serum/plasma levels (vitamin D, B12, folate, zinc, copper, iron,
      ferritin, potassium, calcium, magnesium, and homocysteine) were all considered as
      putative predictors. RESULTS: Substantial nutrient deficiencies pre-treatment
      were observed only for vitamin D (13%) and copper (15%), otherwise most children
      entered the trial with nutrient levels falling within expected ranges. Regression
      analyses showed varying predictors across outcomes with no one predictor being
      consistently identified across different variables. Lower pre-treatment folate
      and B12 levels, being female, greater severity of symptoms and co-occurring
      disorders pre-treatment, more pregnancy complications and fewer birth problems
      were identified as possible predictors of greater improvement for some but not
      all outcome measures although predictive values were weak. Lower IQ and higher
      BMI predicted greater improvement in aggression. CONCLUSIONS: This study
      replicates Rucklidge et al. (2014b) showing the limited value of using serum
      nutrient levels to predict treatment response although we cannot rule out that
      other non-assayed nutrient levels may be more valuable. Additionally, no specific
      demographic or clinical characteristics, including MTHFR genetic status, were
      identified that would preclude children with ADHD from trying this treatment
      approach.

PMID- 30217771
TI  - Associations of the serotonin transporter promoter polymorphism (5-HTTLPR) with
      bipolar disorder and treatment response: A systematic review and meta-analysis.
AB  - BACKGROUND: Associations of the serotonin transporter promoter polymorphism (5
      HTTLPR) with bipolar disorder (BPD) and treatment response in bipolar patients
      were not conclusive. This study not only assessed the association between the 5
      HTTLPR and BPD with accumulating relevant studies, but also in the first time
      evaluated the effect of the 5-HTTLPR on both anti-depressive and anti-manic
      treatment responses in bipolar patients. METHODS: PubMed, Embase, PsycINFO,
      Cochrane Library and Cochrane Control Trials databases were systematically
      searched before February 2017. This meta-analysis followed the PRISMA guidelines.
      RESULTS: A total of 32 population-based studies (5567 cases and 6993 controls)
      and 9 family-based studies (837 trios) were finally screened out and
      statistically joined into a single meta-analysis that revealed an association
      between S allele and an increased risk of BPD (OR = 1.06, p = .038). Pooled
      analysis of the 32 population-based studies indicated an association of S-carrier
      genotypes with an increased risk of BPD (OR = 1.10, p = .029). Meanwhile, the
      association remained significant in Caucasians (OR = 1.15, p = .004), which could
      provide an enough power (88%) to detect a significant association. Regarding the
      treatment response studies, 6 studies reporting the relationship of the 5-HTTLPR
      in anti-depressive remission rate (1034 patients) and 7 studies reporting in
      response rate (1098 patients) were included for pooled analyses. We observed a
      significant association of S-carrier genotypes with a reduced anti-depressive
      remission rate (OR = 0.64, p = .006) but not with anti-depressive response rate.
      The association between the 5-HTTLPR with anti-manic response rate was not
      observed in the included 6 studies (676 patients). CONCLUSIONS: The present study
      supported the presence of a marginal but detectable effect of the 5-HTTLPR on
      susceptibility to BPD. Moreover, the detected association in Caucasian was
      statistically reliable. Besides, the 5-HTTLPR was identified as a useful
      predictor for anti-depressive remission but not for anti-depressive or anti-manic
      response.

PMID- 30217772
TI  - Structural analysis and anthelmintic activity of Canavalia brasiliensis lectin
      reveal molecular correlation between the carbohydrate recognition domain and
      glycans of Haemonchus contortus.
AB  - Haemonchus contortus is one of the most economically important parasites
      infecting small ruminants worldwide. This nematode has shown a great ability to
      develop resistance to anthelmintic drugs, calling for the development of
      alternative control approaches. Because lectins recognize and bind to specific
      carbohydrates and glycan structures present in parasites, they can be considered
      as an alternative to develop new antiparasitic drugs. Accordingly, this work
      aimed to investigate the anthelmintic effect of Canavalia brasiliensis (ConBr)
      lectin against H. contortus and to evaluate a possible interaction of ConBr with
      glycans of this parasite by molecular docking. ConBr showed significant
      inhibition of H. contortus larval development with an IC50 of 0.26 mg mL-1.
      Molecular docking assays revealed that glycans containing the core trimannoside
      [Man(alpha1-3)Man(alpha1-6)Man] of H. contortus interact in the carbohydrate
      recognition domain of ConBr with an interaction value of MDS = -248.77. Our
      findings suggest that the inhibition of H. contortus larval development is
      directly related to the recognition of the core trimannoside present in the
      glycans of these parasites. This work is the first to report on the structure
      function relationships of the anthelmintic activity of plant lectins.

PMID- 30217773
TI  - Post-malaria neurological syndrome: Imported case series and literature review to
      unscramble the auto-immune hypothesis.
AB  - Post-malaria neurological syndrome (PMNS) is a complication that occurs after
      recovery from a severe Plasmodium falciparum attack. Over the past two decades,
      the description of several imported cases has confirmed that this syndrome is a
      clearly distinct entity, different from other post malarial neurological
      disorders. However, the underlying mechanisms are not yet elucidated. Herein, we
      present five imported PMNS cases managed in Marseille, France. The detection of
      neuronal surface antibodies to an encephalitic syndrome of unknown origin allowed
      us to reveal positivity of anti Voltage-Gated-Potassium Channel antibodies (anti
      VGKC) in one of them. Using treatment options from other autoimmune encephalitis
      has to be explored in patients with PMNS.

PMID- 30217774
TI  - A Critical Appraisal of Short-Term End Points in Acute Heart Failure Clinical
      Trials.
AB  - The prevalence of heart failure continues to grow, and this is accompanied by an
      increase in hospitalization for acute heart failure. Hospitalization for heart
      failure results in a trajectory shift of the syndrome and is associated with
      worsening outcomes, increased mortality risk, and high costs. Numerous clinical
      trials over the past 2 decades have had limited success, with no single agent
      shown to improve mortality risk. The lack of success is multifactorial and in
      part related to inadequate targets and end points selected for intervention,
      underscoring the need to better understand and define the pathophysiology of
      acute heart failure. To better inform future drug development, this review
      critically explores the short-term end points and outcomes that previous phase
      III acute heart failure trials have examined.

PMID- 30217775
TI  - Iron catalysis of lipid peroxidation in ferroptosis: Regulated enzymatic or
      random free radical reaction?
AB  - Duality of iron as an essential cofactor of many enzymatic metabolic processes
      and as a catalyst of poorly controlled redox-cycling reactions defines its
      possible biological beneficial and hazardous role in the body. In this review, we
      discuss these two "faces" of iron in a newly conceptualized program of regulated
      cell death, ferroptosis. Ferroptosis is a genetically programmed iron-dependent
      form of regulated cell death driven by enhanced lipid peroxidation and
      insufficient capacity of thiol-dependent mechanisms (glutathione peroxidase 4,
      GPX4) to eliminate hydroperoxy-lipids. We present arguments favoring the
      enzymatic mechanisms of ferroptotically engaged non-heme iron of 15-lipoxygenases
      (15-LOX) in complexes with phosphatidylethanolamine binding protein 1 (PEBP1) as
      a catalyst of highly selective and specific oxidation reactions of arachidonoyl-
      (AA) and adrenoyl-phosphatidylethanolamines (PE). We discuss possible role of
      iron chaperons as control mechanisms for guided iron delivery directly to their
      "protein clients" thus limiting non-enzymatic redox-cycling reactions. We also
      consider opportunities of loosely-bound iron to contribute to the production of
      pro-ferroptotic lipid oxidation products. Finally, we propose a two-stage iron
      dependent mechanism for iron in ferroptosis by combining its catalytic role in
      the 15-LOX-driven production of 15-hydroperoxy-AA-PE (HOO-AA-PE) as well as
      possible involvement of loosely-bound iron in oxidative cleavage of HOO-AA-PE to
      oxidatively truncated electrophiles capable of attacking nucleophilic targets in
      yet to be identified proteins leading to cell demise.

PMID- 30217776
TI  - Team-Based Learning in the Surgery Clerkship: Impact on Student Examination
      Scores, Evaluations, and Perceptions.
AB  - OBJECTIVE: There is little evidence for effectiveness of team-based learning
      (TBL) in specialties such as Surgery. We developed and instituted TBLs in surgery
      clerkship and compared National Board of Medical Examiners (NBME) Surgery Subject
      Exam scores before and after implementation. We also analyzed students' feedback
      for their perception of TBLs. DESIGN, SETTING, AND PARTICIPATNTS: The TBLs were
      transitioned into the curriculum during the 2013-2014 academic year. The "before"
      and "after" implementation periods were 2011-2013 and 2014-2016, respectively.
      NBME Surgery Subject Examination scores at our institution and nationally were
      compared using the independent samples t test. Satisfaction with the clerkship
      was assessed with Association of American Medical Colleges Graduate Questionnaire
      data. Student feedback regarding TBL was gathered at the end of each surgery
      rotation and were analyzed for themes, both positive and negative. RESULTS: Mean
      NBME score was higher at our institution than nationally, both before (77.10 +/-
      8.75vs. 75.20 +/- 8.95, p = 0.032) and after (74.65 +/- 8.0vs. 73.10 +/- 8.55, p
      = 0.071) TBL implementation. The mean score decreased following TBL
      implementation at our medical school (77.10 +/- 8.75vs. 74.65 +/- 8.00, p =
      0.039), but it was also lower nationally (75.20 +/- 8.95vs. 73.10 +/- 8.55, p <
      0.001). Further, students were more likely to rate the surgery clerkship as "good
      and/or excellent" on the Association of American Medical Colleges Graduate
      Questionnaire after TBL implementation (84.6% vs. 73.7%). In qualitative
      assessment, learners stated that TBLs were informative, helpful in studying for
      the shelf exam, and viewed them as an opportunity for interactive learning, and
      thus requested more TBLs. Areas for improvement included reading materials,
      directions, and organization of sessions. CONCLUSIONS: Student perception of TBL
      into our surgery clerkship has been both positive and provided feedback for
      improvement. In addition, our medical school graduates have continued to assess
      their surgery experience as "good" or "excellent" by a large majority.
      Concurrently, our NBME scores remain above the national mean. We believe our
      medical students benefit from a well-organized TBL and its active approach to
      learning during the surgery clerkship with no loss of fundamental surgery
      knowledge.

PMID- 30217777
TI  - Robotic Curriculum Enhances Minimally Invasive General Surgery Residents'
      Education.
AB  - OBJECTIVE: Resident education is evolving as more cases move from open to
      minimally invasive. Many programs struggle to incorporate minimally invasive
      surgery education due to increased operative time and higher cost when residents
      participate. The aim of this paper is to examine if the implementation of a
      robotics curriculum enhances minimally invasive surgical training. DESIGN: A
      retrospective review of all ventral and inguinal hernia cases performed from
      March 2013 to November 2017 was conducted to determine operative technique
      utilized (open, laparoscopic, or robotic) and resident involvement. The study
      cohorts surrounded the introduction of a robotic curriculum in July 2014, and the
      time frames examined were labeled as Before-robotic, After-robotic, and re
      visited examination was done labeled Long-term. SETTING: The study was performed
      at a large quaternary care referral center. PARTICIPANTS: The participants were
      all patients who underwent ventral and inguinal hernia repairs on the general
      surgery, transplant, or colorectal service. RESULTS: Before-robotic had 739
      hernia cases performed: 642 (87%) open, 93 (13%) laparoscopic, and 4 (0.5%)
      robotic. After-robotic had 682 hernia cases performed: 529 (78%) open, 54 (8%)
      laparoscopic, and 99 (15%) robotic. Long-term had 792 hernia cases performed: 603
      (76%) open, 25 (3%) laparoscopic, and 164 (21%) robotic. The general trend was
      towards an institutional decrease in open cases and an increase in robotic hernia
      cases. Resident participation in the robotics cases across all levels increased
      after the implementation of the robotic curriculum. CONCLUSIONS: Implementation
      of a robotic curriculum can enhance minimally invasive surgical training
      experience for general surgery resident education.

PMID- 30217778
TI  - Video-Based Patient Education Improves Patient Attitudes Toward Resident
      Participation in Outpatient Surgical Care.
AB  - OBJECTIVE: Decipher if patient attitudes toward resident participation in
      surgical care can be improved with patient education using a video-based
      modality. DESIGN: A survey using a 5-pt Likert scale was created, piloted, and
      distributed in general and colorectal surgery outpatient clinics that had
      residents involved with patient care at 2 facilities, both with control and
      intervention groups. The intervention group viewed a short video (~4 min)
      explaining the role, education, and responsibilities of medical students,
      residents, and attending surgeons prior to answering the survey. SETTING: General
      and colorectal surgery outpatient clinics at the University of Texas Health San
      Antonio, Texas. PARTICIPANTS: A total of 383 responses were collected, all clinic
      patients were eligible. RESULTS: The majority of patients (82%) welcomed resident
      participation in their health care. Eighteen percent of patients did not expect
      residents to be involved in their care. Patients had favorable views of residents
      participating during their surgical procedures with 77% responding "agree" or
      "strongly agree" to a senior resident assisting with a complicated procedure.
      Patients who viewed the video versus control were less concerned with how much of
      the procedure the resident would perform (76% vs 86%, p = 0.010). Patients who
      viewed the video felt less inconvenienced (p = 0.004). CONCLUSIONS: The majority
      of patients are welcoming to resident participation in their surgical care but
      only 54% were expecting resident involvement at their clinic visit. Early
      explanation with an educational video of resident roles, education, and
      responsibilities may help bridge the gap and improve patient experience.

PMID- 30217779
TI  - A Genomic Variation Map Provides Insights into the Genetic Basis of Spring
      Chinese Cabbage (Brassica rapa ssp. pekinensis) Selection.
AB  - Chinese cabbage is the most consumed leafy crop in East Asian countries. However,
      premature bolting induced by continuous low temperatures severely decreases the
      yield and quality of the Chinese cabbage, and therefore restricts its planting
      season and geographic distribution. In the past 40 years, spring Chinese cabbage
      with strong winterness has been selected to meet the market demand. Here, we
      report a genome variation map of Chinese cabbage generated from the resequencing
      data of 194 geographically diverse accessions of three ecotypes. In-depth
      analyses of the selection sweeps and genome-wide patterns revealed that spring
      Chinese cabbage was selected from a specific population of autumn Chinese cabbage
      around the area of Shandong peninsula in northern China. We identified 23 genomic
      loci that underwent intensive selection, and further demonstrated by gene
      expression and haplotype analyses that the incorporation of elite alleles of
      VERNALISATION INSENTIVE 3.1 (BrVIN3.1) and FLOWER LOCUS C 1 (BrFLC1) is a
      determinant genetic source of variation during selection. Moreover, we showed
      that the quantitative response of BrVIN3.1 to cold due to the sequence variations
      in the cis elements of the BrVIN3.1 promoter significantly contributes to bolting
      time variation in Chinese cabbage. Collectively, our study provides valuable
      insights into the genetic basis of spring Chinese cabbage selection and will
      facilitate the breeding of bolting-resistant varieties by molecular-marker
      assisted selection, transgenic or gene editing approaches.

PMID- 30217780
TI  - Alignment Risk Factors for Proximal Junctional Kyphosis and the Effect of Lower
      Thoracic Junctional Tethers for Adult Spinal Deformity.
AB  - OBJECTIVE: The aims of this retrospective cohort study were to 1) identify new
      alignment risk factors for proximal junctional kyphosis (PJK) in adult spinal
      deformity (ASD) patients with lower thoracic upper instrumented vertebra (UIV)
      and 2) determine the effect of junctional tethers on PJK and UIV alignment.
      METHODS: We analyzed consecutive ASD patients who underwent posterior
      instrumented fusion with lower thoracic UIV (T9-T11). Posteriorly anchored
      junctional tethers were used more recently for ligamentous augmentation to
      prevent PJK. In addition to regional and global parameters, upper segmental
      lumbar lordosis (ULL) versus lower segmental lumbar lordosis and UIV angle
      (measured from UIV inferior endplate to horizontal) were assessed. Primary
      outcome of PJK was defined as proximal junctional angle >10 degrees  and >10
      degrees  greater than the corresponding preoperative measurement. Univariable and
      multivariable analyses were performed. RESULTS: The study cohort comprised 120
      ASD patients (mean age, 67 years) with minimum 1-year follow-up. Preoperative ULL
      (P = 0.034) and UIV angle (P = 0.026) were associated with PJK. No independent
      preoperative alignment risk factors of PJK were identified in multivariable
      analysis. Tether use was protective against PJK (odds ratio, 0.063 [0.016-0.247];
      P < 0.001). PJK in tethered patients was more common with greater postoperative
      ULL (P = 0.047) and UIV angle (P = 0.026). CONCLUSIONS: Junctional tethers
      significantly reduced PJK in ASD patients with lower thoracic UIV. In tethered
      patients, PJK was more common with greater postoperative lordosis of the upper
      lumbar spine and greater UIV angle. This finding suggests potential benefit of
      tethers to mitigate effects of segmental lumbar and focal UIV malalignment that
      may occur after deformity surgery.

PMID- 30217781
TI  - Minimally Invasive Interhemispheric Approach for Giant Olfactory Groove
      Meningioma: Technical Note.
AB  - BACKGROUND: Skull base tumors, such as large olfactory groove meningiomas (OGMs),
      are a challenge for neurosurgeons. However, the tendency to reduce invasive
      surgeries is gaining more adepts. We describe a minimally invasive
      interhemispheric approach with a falx window for microsurgical resection of the
      giant OGM as a technical note. METHODS: A minimal medial frontal craniotomy
      measuring 3-5 cm in size is performed, and an interhemispheric approach is
      combined with an opening in the falx to improve microsurgical resection of the
      giant OGM. The technique and more details are described. RESULTS: A minimally
      invasive interhemispheric approach with a falx window was performed in this case.
      Gross total resection of the OGM was possible with minimal brain retraction.
      Simpson grade I was achieved, and there was a good outcome on the postoperative
      recovery period of the patient, with vision improvement, preservation of
      olfaction, and no other complications. CONCLUSIONS: The minimally invasive
      interhemispheric approach with a falx window is effective and safe for giant OGM
      with a good outcome for the patient. The opening in the falx improves the
      interhemispheric pathway and allows gross total resection with minimal brain
      retraction and low morbidity.

PMID- 30217782
TI  - Impact of connector placement and design on bending stiffness of spinal
      constructs.
AB  - OBJECTIVE: To evaluate the stability of multiple rod-connector construct designs
      using a mechanical 4-point bending testing frame. METHODS: A mechanical study was
      used to evaluate the bending stiffness of 3 connectors across 12 different
      configurations of rod-connector-rod constructs. Stability was evaluated in
      flexion-extension and lateral bending. Combinations of rods having 1 of 3
      diameters (4.0 mm, 5.5 mm, and 6.0 mm) connected by 1 of 3 connector types
      (parallel open, snap-on, and hinged) were compared. Configurations with single
      connectors and with double connectors with variable spacing were also compared to
      simulate revision surgery conditions. RESULTS: Constructs consisting of 4.0-mm
      rods connected to 4.0-mm rods were significantly less stiff as the total number
      of connectors used in a series exceeded 2. When single-connector configurations
      were compared, parallel open rod connectors demonstrated greater stiffness in
      flexion-extension than hinged open connectors, whereas hinged open connectors
      demonstrated greater stiffness in lateral bending. Using double connectors
      increased stiffness of 4.0-to-4.0-mm rod configurations in flexion-extension and
      lateral bending, 4.0-to-6.0-mm rod configurations in flexion-extension, and 5.5
      to-6.0-mm rod configurations in lateral bending. Spacing the double connectors
      significantly improved lateral bending stiffness of 4.0-to-4.0-mm and 5.5-to-6.0
      mm rod configurations. CONCLUSIONS: Our data indicate that the design, number,
      and placement of rod connectors have a significant impact on the bending
      stiffness of a surgical construct. Such mechanical data may influence construct
      design in primary and revision surgeries of the cervical spine and
      cervicothoracic junction.

PMID- 30217783
TI  - Ventricular Volume Dynamics During the Development of Adult Chronic Communicating
      Hydrocephalus in a Rodent Model.
AB  - INTRODUCTION: The pathophysiology of normal-pressure hydrocephalus and the
      correlation with its symptomatology is not well understood. OBJECTIVE: To monitor
      and evaluate the enlargement patterns of the ventricular system for each
      ventricle and its correlation with the presenting symptoms. METHODS: Bilateral
      kaolin injection into the subarachnoid space overlying the cranial convexities
      was done in 18 adult rats. Magnetic resonance imaging was performed on an 11.7-T
      scanner 15, 60, 90, and 120 days after injection. Volumes of the ventricular
      system were measured for each ventricle and correlated with biweekly behavioral
      findings. RESULTS: There was a progressive increase in the ventricular volume for
      the lateral ventricles since day 15 in the kaolin-injected animals. There was a
      nonsignificant trend in volume growth for the third ventricle, but its
      enlargement was synchronous with the lateral ventricles. No significant change
      for the fourth ventricle. No symptoms were detected in the first 60 days.
      Association was found between the ventricular volume and locomotor changes. In
      addition, the odds of locomotor symptoms increased by 3% for every additional
      cubic millimeter of volume in the left (P < 0.001) and right (P = 0.023)
      ventricles, and for the total magnetic resonance imaging volume by 1% (P =
      0.013). CONCLUSIONS: Expansion of the lateral ventricles maintained similar
      proportions over time, accompanied by a synchronous third ventricular expansion
      with less proportion and a nonsignificant fourth enlargement. Lateral ventricles
      enlarged most in those animals that were to develop late locomotor deterioration.
      Further research using this animal model combined with different radiologic
      imaging techniques, such as diffusion tensor imaging and perfusion studies, is
      recommended.

PMID- 30217784
TI  - Estimating testosterone concentrations in adolescent girls: Comparison of two
      direct immunoassays to liquid chromatography-tandem mass spectrometry.
AB  - CONTEXT: The appropriate role of direct total testosterone (T) immunoassays in
      reproductive research is controversial. OBJECTIVE: To assess the concordance
      between two direct immunoassays and a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) assay for total T in adolescent girls with measured
      concentrations < 50 ng/dl. DESIGN: Cross-sectional analysis. SETTING: Academic
      medical center. PARTICIPANTS: Adolescent girls (age 8.4-18.1 years) participating
      in clinical research protocols. INTERVENTION: Paired blood samples were obtained
      for total T by LC-MS/MS (n = 66; Mayo Clinic Laboratory) and by direct
      immunoassay (Center for Research in Reproduction)-either radioimmunoassay (RIA; n
      = 31) or chemiluminescence immunoassay (CLIA; n = 35). At the time of assay,
      laboratories were unaware that results would be compared. MAIN OUTCOME MEASURE:
      Measurement agreement between immunoassay and LC-MS/MS. RESULTS: Measured T
      concentrations (LC-MS/MS) were <7 to 44 ng/dl. The average difference between RIA
      and LC-MS/MS was 0.84 [-0.89, 2.56] ng/dl (mean [95% confidence interval]). RIA
      correlated very strongly with LC-MS/MS (r = 0.899; p < 0.0001); and both Deming
      regression and Bland-Altman analysis suggested no bias. The average difference
      between chemiluminescence and LC-MS/MS was 1.39 [-0.83, 3.60] ng/dl. CLIA
      correlated strongly with LC-MS/MS (r = 0.806; p < 0.0001). While Bland-Altman
      analysis suggested no systematic bias, Deming regression analysis suggested that,
      as measured values increased, values obtained by CLIA tended to be progressively,
      albeit only modestly, higher than those obtained by LC-MS/MS. CONCLUSIONS: These
      data support the use of rigorously-performed and carefully-validated direct T
      immunoassays in high-quality endocrine research in peripubertal adolescent girls.

PMID- 30217785
TI  - The sulfatase pathway as estrogen supply in endometrial cancer.
AB  - OBJECTIVE: Contradictory results are reported about the level of steroid
      sulfatase (STS), estrogen sulfotransferase (SULT1E1; together, the sulfatase
      pathway) and aromatase (CYP19A1) in endometrial cancer (EC). The aim of this
      study was to explore the levels of these enzymes in a well-characterized cohort
      of EC patients and postmenopausal controls. MATERIALS AND METHODS: Endometrial
      tissues from 31 EC patients (21 grade 1 and 10 grade 2-3) and 19 postmenopausal
      controls were collected. Levels of mRNA (RT-qPCR) and protein
      (immunohistochemistry) were determined. STS enzyme activity was measured by HPLC,
      whereas SULT1E1 enzyme activity was determined using a novel method based on
      liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: No significant
      differences in STS, SULT1E1 mRNA or protein levels and STS:SULT1E1 ratio were
      found. STS enzyme activity and STS:SULT1E1 activity ratio were significantly
      decreased in ECs compared with controls. CYP19A1 mRNA levels were lower in ECs
      than in controls. CONCLUSION: A novel highly sensitive and accurate protocol to
      assess SULT1E1 activity is presented. STS enzyme activity and the STS:SULT1E1
      activity ratio seem to be lower in ECs than in controls. STS is an important
      route for estrogen supply in endometrial cells.

PMID- 30217786
TI  - Lysophosphatidylcholine induces expression of genes involved in cholesterol
      biosynthesis in THP-1 derived macrophages.
AB  - Lysophosphatidylcholine (LPC), a major component of oxidized low-density
      lipoprotein, is associated with atherosclerosis, obesity, stroke, and cancer.
      However, the direction and mechanism of this relationship remains unclear. In
      this study, we conducted RNA profiling in THP-1 derived macrophages treated with
      LPC and uncovered a relationship between LPC and the cholesterol biosynthesis
      pathway. Principal component analysis (PCA) of RNA profiling showed that
      untreated THP-1 cells and those treated with 10, 20, or 40 uM LPC were distinctly
      distributed. Functional annotation revealed that LPC affected the expression of
      genes involved in cytokine-cytokine receptor interaction, TNF signaling, and MAPK
      signaling. Interestingly, LPC also altered the expression of 11 genes involved in
      cholesterol synthesis such as those in terpenoid backbone biosynthesis and
      steroid biosynthesis pathways. This increased gene expression occurred in a dose
      dependent manner in response to LPC treatment. Especially, LPC with saturated
      acyl groups enhanced the expression of these genes compared to LPC with
      unsaturated acyl groups, and similar results were shown in response to saturated
      and unsaturated free fatty acids. Our findings demonstrate that LPCs with
      saturated acyl groups induce the expression of genes involved in cholesterol
      biosynthesis and may have implications for cholesterol related diseases.

PMID- 30217787
TI  - Bile acids: Lipase-catalyzed synthesis of new hyodeoxycholic acid derivatives.
AB  - In this work we present an efficient, environmentally friendly approach to the
      synthesis of a series of hyodeoxycholic acid derivatives applying Biocatalysis.
      Fifteen acetyl and ester derivatives, twelve of them new, were obtained through
      an enzymatic strategy in a fully regioselective way and in very good to excellent
      yield. In order to find the optimal reaction conditions, the influence of several
      parameters such as enzyme source, alcohol or acylating agent:substrate ratio,
      enzyme:substrate ratio, temperature and reaction solvent was considered. The
      excellent results obtained made this procedure very efficient, particularly
      considering the low amount of enzyme required. In addition, this methodology uses
      mild reaction conditions and has reduced environmental impact, making
      biocatalysis a suitable way to obtaining these bile acids derivatives.

PMID- 30217788
TI  - Ichnocarpus frutescens (L.) R. Br. root derived phyto-steroids defends
      inflammation and algesia by pulling down the pro-inflammatory and nociceptive
      pain mediators: An in-vitro and in-vivo appraisal.
AB  - Ichnocarpus frutescens, a climber plant, is distributed all over India. As its
      different parts are used as anti-inflammatory agent, so we re-investigated the
      roots to isolate compounds and evaluate its biological efficacy. Also, in-silico
      molecular docking was carried out to elucidate the structure activity
      relationship (SAR) of isolated compounds toward identifies the drug target enzyme
      with validation, which was further supported by anti-inflammatory in-vitro and in
      vivo experimental models. The compounds have been undertaken mainly to
      investigate the anti-inflammatory and analgesic efficacy along with molecular
      docking investigation followed by anti-proteinase, anti-denaturation and
      cyclooxygenase (COX) inhibition studies. Inflammatory cytokines like TNF-alpha
      and IL-6 were assayed from lipopolysaccharides (LPS) and Concavallin (CON A)
      stimulated human PBMC derived macrophages by Enyme linked immune sorbent assay
      (ELISA) method. The purity index of the lead compound was determined by HPLC. The
      compounds were illustrated as 2-hydroxy tricosanoic acid (1), stigmasterol
      glucoside (2), stigmasterol (3), beta-sitosterol (4) and beta-sitosterol
      glucoside (5). The test molecules showed significant anti-denaturation, anti
      proteinase and analgesic effect validated with docking study. Compounds exhibited
      anti-inflammatory and pain killing action due to dexamethasone like phytosterol
      property. Promising anti-denaturation and anti-proteinase activity offered by the
      compound 5, may hold its promise to fight against arthritis by rejuvenating the
      osteoblast cells and destroying the bone-resorpting complex of hydrated protein,
      bone minerals by secreting the acid and an enzyme collagenase along with pain
      management. The lead bioactive compound i.e. beta-sitosterol glucoside (compound
      5) demonstrated considerable anti-inflammatory activity showing more than 90%
      protection against the inflammatory cytokines at 50 uM dose. The anti
      denaturation and COX-2 inhibition shown by the compound 5 was also noteworthy
      with the significant IC50 (ranging from 0.25 to 2.56 uM) that also supporting its
      future promise for developing as anti-inflammatory agent. Since the most bio
      active compound (5) elicit promising acute anti-inflammatory action and
      peripheral anti-nociceptive pain killing action with a significant ED50 dose of
      3.95 & 2.84 mg/kg i.p. respectively in the in-vivo animal model. It could suggest
      its potentiality as a good in-vivo bio available agent to be an emerging anti
      inflammatory drug regimen scaffold in the future. It also establishes significant
      in-vitro and in-vivo result co-relation. Therefore, the compound 5 could be
      believed as a potent lead for designing anti-inflammatory, anti-arthritic drug or
      pain killer without showing any untoward effect.

PMID- 30217789
TI  - Antimicrobial activity of Elytropappus rhinocerotis (Asteraceae) against micro
      organisms associated with foot odour and skin ailments.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The twigs of Elytropappus rhinocerotis are widely
      used in the Cape region of South Africa to treat foot odour, perspiration and
      also itchy, chilblained and burning feet. However, no antimicrobial studies have
      hitherto been published on this popular Cape herbal medicine, which is also used
      for a wide range of ailments. AIMS OF THE STUDY: To determine the antimicrobial
      activity of the extracts, essential oil and two major labdane diterpenes isolated
      from E. rhinocerotis against micro-organisms associated with foot odour and other
      conditions associated with skin infections. MATERIALS AND METHODS: Leafy stems
      were harvested from three individual plants at three separate geographical
      localities, giving a total of nine plant samples. The samples were air-dried,
      powdered and extracted with a 1:1 mixture of methanol and dichloromethane, and
      also with sterile distilled water. A portion of each sample was also
      hydrodistilled to obtain nine samples of essential oil. Isolation of the major
      labdane diterpenes was performed using silica and ethyl acetate in hexane (3:7
      v/v) as the mobile phase. Minimum inhibitory concentrations (MIC) were determined
      for nine crude extracts, as well as three essential oil samples and two labdane
      diterpenes obtained from a bulk sample. The test organisms used in this study
      were from Deutsche Sammlung von Mikrooganismen (DSM) and American type culture
      collection (ATCC) strains and included five bacterial species (Brevibacterium
      agri ATCC 51663, B. epidermidis DSM 20660, B. linens DSM 20425, Staphylococcus
      aureus ATCC 25923, S. epidermidis ATCC 12228) and one fungal species
      (Trichophyton mentagrophytes ATCC 9533) associated with the skin. RESULTS: The
      presence of essential oil is reported for the first time. Organic extracts and
      essential oil samples showed moderate to noteworthy activity against selected
      test organisms. For the Brevibacteria, the lowest MIC values for phenolic
      extracts were several times lower than the corresponding values for the positive
      control zinc (shown in brackets): 0.0031 mg/mL against Brevibacterium agri (0.33
      mg/mL), 0.17 mg/mL against B. epidermidis (3.91 mg/mL) - both for sample 2 of
      Vanwyksdorp; 0.13 mg/mL against B. linens (2.28 mg/mL) - for sample 3 of
      Vanwyksdorp. Two isolated labdane diterpenoids (one of which is here first
      reported) were also antimicrobially tested and showed moderate activity but had
      high abundance in the extracts. Two major monoterpenes and four sesquiterpenes in
      the essential oil were identified as 1,8-cineole (4.6-12.3%), terpinen-4-ol (9.2
      24.3%), germacrene A (3.9-15.6%), (-)-spathulenol (1.7-37.8%), viridiflorol (0.3
      100%), and silphiperfol-6-en-5-one (4.5-26.8%). CONCLUSION: The antimicrobial
      results particularly for the essential oils and against the Brevibacteria support
      the traditional topical use of Elytropappus rhinocerotis twigs to treat foot
      perspiration, foot odour and other related skin conditions.

PMID- 30217790
TI  - Origanum majorana L extract exhibit positive cooperative effects on the main
      mechanisms involved in acute infectious diarrhea.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Origanum majorana L. (Lamiaceae) is commonly used
      in Moroccan folk medicine to treat infantile colic, abdominal discomfort and
      diarrhea. Liquid stools and abdominal discomfort observed in acute infectious
      diarrhea are the consequences of imbalance between intestinal water secretion and
      absorption in the lumen, and relaxation of smooth muscle surrounding the
      intestinal mucosa. AIM OF THE STUDY: The objective of our study was to see if
      aqueous extract of Origanum majorana L. (AEOM) may exhibit an effect on those
      deleterious mechanisms. MATERIALS AND METHODS: The effect of AEOM on electrogenic
      Cl- secretion and Na+ absorption, the two main mechanisms underlying water
      movement in the intestine, was assessed on intestinal pieces of mice intestine
      mounted, in vitro, in Ussing chambers. AEOM effect on muscle relaxation was
      measured on rat intestinal smooth muscle mounted in an isotonic transducer.
      RESULTS: 1) AEOM placed on the serosal (i.e. blood) side of the piece of jejunum
      entirely inhibited in a concentration-dependent manner the Forskolin-induced
      electrogenic chloride secretion, with an IC50 = 654 +/- 8ug/mL. 2) AEOM placed on
      the mucosal (i.e. luminal) side stimulated in a concentration-dependent manner an
      electrogenic Na+ absorption, with an IC50 = 476.9 +/- 1ug/mL. 3) AEOM (1mg/mL)
      inhibition of Forskolin-induced electrogenic secretion was almost entirely
      prevented by prior exposure to Ca++ channels or neurotransmitters inhibitors. 4)
      AEOM (1mg/mL) proabsorptive effect was greater in the ileum and progressively
      declined in the jejunum, distal colon and proximal colon (minimal). 5) AEOM
      inhibited in a concentration-dependent manner smooth muscle Carbachol or KCl
      induced contraction, with an IC50 = 1.64 +/- 0.2mg/mL or 1.92 +/- 0.8mg/mL,
      respectively. CONCLUSION: the present results indicate that aqueous extract of
      Origanum majorana L. exhibit positive cooperative effects on the main mechanisms
      that are involved in acute infectious diarrhea.

PMID- 30217791
TI  - Safety profile after prolonged C3 inhibition.
AB  - The central component of the complement cascade, C3, is involved in various
      biological functions, including opsonization of foreign bodies, clearance of
      waste material, activation of immune cells, and triggering of pathways
      controlling development. Given its broad role in immune responses, particularly
      in phagocytosis and the clearance of microbes, a deficiency in complement C3 in
      humans is often associated with multiple bacterial infections. Interestingly, an
      increased susceptibility to infections appears to occur mainly in the first two
      years of life and then wanes throughout adulthood. In view of the well
      established connection between C3 deficiency and infections, therapeutic
      inhibition of complement at the level of C3 is often considered with caution or
      disregarded. We therefore set out to investigate the immune and biochemical
      profile of non-human primates under prolonged treatment with the C3 inhibitor
      compstatin (Cp40 analog). Cynomolgus monkeys were dosed subcutaneously with Cp40,
      resulting in systemic inhibition of C3, for 1 week, 2 weeks, or 3 months. Plasma
      concentrations of both C3 and Cp40 were measured periodically and complete
      saturation of plasma C3 was confirmed. No differences in hematological,
      biochemical, or immunological parameters were identified in the blood or tissues
      of animals treated with Cp40 when compared to those injected with vehicle alone.
      Further, skin wounds showed no signs of infection in those treated with Cp40. In
      fact, Cp40 treatment was associated with a trend toward accelerated wound healing
      when compared with the control group. In addition, a biodistribution study in a
      rhesus monkey indicated that the distribution of Cp40 in the body is associated
      with the presence of C3, concentrating in organs that accumulate blood and
      produce C3. Overall, our data suggest that systemic C3 inhibition in healthy
      adult non-human primates is not associated with a weakened immune system or
      susceptibility to infections.

PMID- 30217792
TI  - Discordance Between Human Papillomavirus Twitter Images and Disparities in Human
      Papillomavirus Risk and Disease in the United States: Mixed-Methods Analysis.
AB  - BACKGROUND: Racial and ethnic minorities are disproportionately affected by human
      papillomavirus (HPV)-related cancer, many of which could have been prevented with
      vaccination. Yet, the initiation and completion rates of HPV vaccination remain
      low among these populations. Given the importance of social media platforms for
      health communication, we examined US-based HPV images on Twitter. We explored
      inconsistencies between the demographics represented in HPV images and the
      populations that experience the greatest burden of HPV-related disease.
      OBJECTIVE: The objective of our study was to observe whether HPV images on
      Twitter reflect the actual burden of disease by select demographics and determine
      to what extent Twitter accounts utilized images that reflect the burden of
      disease in their health communication messages. METHODS: We identified 456 image
      tweets about HPV that contained faces posted by US users between November 11,
      2014 and August 8, 2016. We identified images containing at least one human face
      and utilized Face++ software to automatically extract the gender, age, and race
      of each face. We manually annotated the source accounts of these tweets into 3
      types as follows: government (38/298, 12.8%), organizations (161/298, 54.0%), and
      individual (99/298, 33.2%) and topics (news, health, and other) to examine how
      images varied by message source. RESULTS: Findings reflected the racial
      demographics of the US population but not the disease burden (795/1219, 65.22%
      white faces; 140/1219, 11.48% black faces; 71/1219, 5.82% Asian faces; and
      213/1219, 17.47% racially ambiguous faces). Gender disparities were evident in
      the image faces; 71.70% (874/1219) represented female faces, whereas only 27.89%
      (340/1219) represented male faces. Among the 11-26 years age group recommended to
      receive HPV vaccine, HPV images contained more female-only faces (214/616, 34.3%)
      than males (37/616, 6.0%); the remainder of images included both male and female
      faces (365/616, 59.3%). Gender and racial disparities were present across
      different image sources. Faces from government sources were more likely to depict
      females (n=44) compared with males (n=16). Of male faces, 80% (12/15) of youth
      and 100% (1/1) of adults were white. News organization sources depicted high
      proportions of white faces (28/38, 97% of female youth and 12/12, 100% of adult
      males). Face++ identified fewer faces compared with manual annotation because of
      limitations with detecting multiple, small, or blurry faces. Nonetheless, Face++
      achieved a high degree of accuracy with respect to gender, race, and age compared
      with manual annotation. CONCLUSIONS: This study reveals critical differences
      between the demographics reflected in HPV images and the actual burden of
      disease. Racial minorities are less likely to appear in HPV images despite higher
      rates of HPV incidence. Health communication efforts need to represent
      populations at risk better if we seek to reduce disparities in HPV infection.

PMID- 30217794
TI  - NHS lacks the resources to keep re-testing for non-alcoholic fatty liver disease.

PMID- 30217793
TI  - Using Partially-Observed Facebook Networks to Develop a Peer-Based HIV Prevention
      Intervention: Case Study.
AB  - BACKGROUND: This is a case study from an HIV prevention project among young black
      men who have sex with men. Individual-level prevention interventions have had
      limited success among young black men who have sex with men, a population that is
      disproportionately affected by HIV; peer network-based interventions are a
      promising alternative. Facebook is an attractive digital platform because it
      enables broad characterization of social networks. There are, however, several
      challenges in using Facebook data for peer interventions, including the large
      size of Facebook networks, difficulty in assessing appropriate methods to
      identify candidate peer change agents, boundary specification issues, and partial
      observation of social network data. OBJECTIVE: This study aimed to explore
      methodological challenges in using social Facebook networks to design peer
      network-based interventions for HIV prevention and present techniques to overcome
      these challenges. METHODS: Our sample included 298 uConnect study respondents who
      answered a bio-behavioral survey in person and whose Facebook friend lists were
      downloaded (2013-2014). The study participants had over 180,000 total Facebook
      friends who were not involved in the study (nonrespondents). We did not observe
      friendships between these nonrespondents. Given the large number of
      nonrespondents whose networks were partially observed, a relational boundary was
      specified to select nonrespondents who were well connected to the study
      respondents and who may be more likely to influence the health behaviors of young
      black men who have sex with men. A stochastic model-based imputation technique,
      derived from the exponential random graph models, was applied to simulate 100
      networks where unobserved friendships between nonrespondents were imputed. To
      identify peer change agents, the eigenvector centrality and keyplayer positive
      algorithms were used; both algorithms are suitable for identifying individuals in
      key network positions for information diffusion. For both algorithms, we assessed
      the sensitivity of identified peer change agents to the imputation model, the
      stability of identified peer change agents across the imputed networks, and the
      effect of the boundary specification on the identification of peer change agents.
      RESULTS: All respondents and 78.9% (183/232) of nonrespondents selected as peer
      change agents by eigenvector on the imputed networks were also selected as peer
      change agents on the observed networks. For keyplayer, the agreement was much
      lower; 42.7% (47/110) and 35.3% (110/312) of respondent and nonrespondent peer
      change agents, respectively, selected on the imputed networks were also selected
      on the observed network. Eigenvector also produced a stable set of peer change
      agents across the 100 imputed networks and was much less sensitive to the
      specified relational boundary. CONCLUSIONS: Although we do not have a gold
      standard indicating which algorithm produces the most optimal set of peer change
      agents, the lower sensitivity of eigenvector centrality to key assumptions leads
      us to conclude that it may be preferable. The methods we employed to address the
      challenges in using Facebook networks may prove timely, given the rapidly
      increasing interest in using online social networks to improve population health.

PMID- 30217795
TI  - Blood manufacturing methods affect red blood cell product characteristics and
      immunomodulatory activity.
AB  - Transfusion of red cell concentrates (RCCs) is associated with increased risk of
      adverse outcomes that may be affected by different blood manufacturing methods
      and the presence of extracellular vesicles (EVs). We investigated the effect of
      different manufacturing methods on hemolysis, residual cells, cell-derived EVs,
      and immunomodulatory effects on monocyte activity. Thirty-two RCC units produced
      using whole blood filtration (WBF), red cell filtration (RCF), apheresis-derived
      (AD), and whole blood-derived (WBD) methods were examined (n = 8 per method).
      Residual platelet and white blood cells (WBCs) and the concentration, cell of
      origin, and characterization of EVs in RCC supernatants were assessed in fresh
      and stored supernatants. Immunomodulatory activity of RCC supernatants was
      assessed by quantifying monocyte cytokine production capacity in an in vitro
      transfusion model. RCF units yielded the lowest number of platelet and WBC
      derived EVs, whereas the highest number of platelet EVs was in AD (day 5) and in
      WBD (day 42). The number of small EVs (<200 nm) was greater than large EVs (>=200
      nm) in all tested supernatants, and the highest level of small EVs were in AD
      units. Immunomodulatory activity was mixed, with evidence of both inflammatory
      and immunosuppressive effects. Monocytes produced more inflammatory interleukin-8
      after exposure to fresh WBF or expired WBD supernatants. Exposure to supernatants
      from AD and WBD RCC suppressed monocyte lipopolysaccharide-induced cytokine
      production. Manufacturing methods significantly affect RCC unit EV
      characteristics and are associated with an immunomodulatory effect of RCC
      supernatants, which may affect the quality and safety of RCCs.

PMID- 30217797
TI  - Management of oesophageal intramucosal carcinoma.
AB  - We present an interesting case of an intramucosal carcinoma (IMC) in the setting
      of Barrett's oesophagus in a 66-year-old woman. Her clinical course highlights
      the shifting paradigm in the approach to management of Barrett's oesophagus and
      IMC. With innovation in imaging and endoscopic treatment modalities, patients are
      detected earlier and managed prior to development of malignancy. The patient was
      treated with endoscopic modalities, and after 3 years' follow-up, she remains
      recurrence free.

PMID- 30217796
TI  - Distinct Roles of Two Histone Methyltransferases in Transmitting H3K36me3-Based
      Epigenetic Memory Across Generations in Caenorhabditis elegans.
AB  - Epigenetic information contributes to proper gene expression and development, and
      can be transmitted not only through mitotic divisions but also from parents to
      progeny. We investigated the roles in epigenetic inheritance of MES-4 and MET-1,
      the two Caenorhabditis elegans enzymes that methylate H3K36 (histone H3 Lys 36).
      Mass spectrometry analysis confirmed immunostaining results showing that both MES
      4 and MET-1 catalyze H3K36me3. In the adult germline, MES-4 is enriched in the
      distal mitotic zone and MET-1 is enriched in the meiotic pachytene zone. Embryos
      inherit H3K36me3-marked chromosomes from both the oocyte and sperm, and a
      maternal load of MES-4 and MET-1 Maternal MES-4 quickly associates with sperm
      chromosomes; that association requires that the sperm chromosomes bear H3K36me3,
      suggesting that MES-4 is recruited to chromosomes by preexisting H3K36me3. In
      embryos that inherit H3K36me3-positive oocyte chromosomes and H3K36me3-negative
      sperm chromosomes, MES-4 and H3K36me3 are maintained on only a subset of
      chromosomes until at least the 32-cell stage, likely because MES-4 propagates
      H3K36me3 on regions of the genome with preexisting H3K36me3. In embryos lacking
      MES-4, H3K36me3 levels on chromosomes drop precipitously postfertilization. In
      contrast to the relatively high levels of MES-4 in early-stage embryos, MET-1
      levels are low at early stages and start increasing by the ~26-cell stage,
      consistent with expression from the zygotic genome. Our findings support the
      model that MET-1 mediates transcription-coupled H3K36me3 in the parental germline
      and transcriptionally active embryos, and that MES-4 transmits an epigenetic
      memory of H3K36me3 across generations and through early embryo cell divisions by
      maintaining inherited patterns of H3K36me3.

PMID- 30217798
TI  - Uncommon cause of chest pain in a postoperative spinal patient.
AB  - An 84-year-old woman with previous spinal operations including vertebroplasty and
      lumbar decompressions was admitted electively under the spinal team for right
      sided L4/5 decompression for worsening back pain which she undergoes using a
      posterior approach. Postoperatively, she develops stabbing upper central chest
      pain and given unremarkable chest X-ray, ECG and cardiac troponin, she undergoes
      a CT pulmonary angiogram which shows a fracture of the upper part of sternum but
      no pulmonary embolism. There is no history of recent trauma and this is deemed to
      be secondary to prolonged spinal surgery in the prone position in a patient with
      osteopenic bones. To date, we have not come across a case of spontaneous sternal
      fracture as a complication of spinal surgery at our regional spinal unit. Most
      cases of sternal fractures are secondary to blunt anterior chest wall trauma with
      spontaneous fractures and stress fractures being rare.

PMID- 30217799
TI  - A rare case of cellular angiofibroma affecting the periurethral region in a 38
      year-old woman.
AB  - Cellular angiofibroma (CAF) is a rare, site-specific, benign mesenchymal tumour
      affecting both women and men in the genitourinary region. The tumour usually
      presents as a small, asymptomatic lesion involving the vulvovaginal regions in
      women and inguinoscrotal regions in men. We report the case of a 38-year-old
      woman presenting with a painless mass in the vulval region, especially on the
      right side of urethral meatus for 8 years with progressively increasing lower
      abdominal discomfort. A simple excision was performed. The diagnosis of CAF was
      confirmed histopathologically.

PMID- 30217800
TI  - Cytomegalovirus-associated haemophagocytic lymphohistiocytosis: a rare cause of
      febrile neutropenia during cancer chemotherapy.
AB  - Febrile neutropenia (FN) is a common complication in patients with cancer during
      treatment with antineoplastic drugs. The initial cause is usually bacterial, and
      treatment of FN follows well-defined algorithms. We report a case of a 62-year
      old patient with chronic lymphocytic leukaemia (CLL), who developed FN, which was
      unresponsive to both empirical antibacterial and empirical antifungal therapy.
      Surprisingly, a diagnosis of the life-threatening condition haemophagocytic
      lymphohistiocytosis (HLH) associated with cytomegalovirus (CMV) infection was
      made and treated successfully. CMV-associated HLH has not previously been
      described in patients with CLL treated with rituximab and bendamustine. It is
      concluded that HLH should be considered in patients with cancer with FN not
      responding to conventional antibiotic therapy.

PMID- 30217801
TI  - Coronary artery ectasia: a rare cause of acute coronary syndrome.
AB  - Coronary artery ectasia (CAE) is defined as a localised or diffuse dilatation of
      coronary artery lumen more than 1.5 times that of an adjacent normal segment. CAE
      may present with or without functionally significant stenosis. Such patients may
      manifest with stable angina or with acute coronary syndrome. Ectasia may serve as
      a nidus for thrombus formation with likelihood of distal embolisation or it may
      lead to dissection or spasm. This condition presents a challenge for an
      interventionist. Should we intervene or manage it medically. We describe a case
      of CAE where all the vessels were diffusely ectatic with variable degree of
      stenosis. In brief we discuss the causes and management issues in ectasia.

PMID- 30217802
TI  - Cervical tuberculous lymphadenitis in an elderly adult.

PMID- 30217803
TI  - Pineoblastoma in a child with 22q11.2 deletion syndrome.

PMID- 30217804
TI  - Patella incarceration with associated patella fracture: a rare case of a
      paediatric patient with no associated femoral fracture.
AB  - We describe the case of a 15-year-old girl who presented to the Accident and
      Emergency Department with right knee pain and a tense effusion following a twist
      and fall directly onto her right knee. An MRI scan demonstrated that she had an
      incarcerated dislocated patella with an associated patella avulsion fracture.
      This required open reduction. Open reduction and fixation was performed using
      suture anchors. We feel that this case is particularly pertinent since nearly all
      previous case reports describe an incarcerated patella with an associated femur
      fracture. Furthermore, no previous case reports have been published in a child.

PMID- 30217805
TI  - Spin-top-like encrustation of suprapubic cystostomy catheter: when proper
      counselling is all that it takes!

PMID- 30217806
TI  - Tibial osteomyelitis with cold abscess within calf muscles in a toddler referred
      with suspected oligoarthritis to rheumatology clinic.

PMID- 30217808
TI  - A Quality Improvement Initiative: Reducing Blood Culture Contamination in a
      Children's Hospital.
AB  - BACKGROUND AND OBJECTIVE: Blood culture contamination is a safety and quality
      concern in children's hospitals; it leads to increased unnecessary testing,
      admissions, antibiotic exposure, and cost. The standard benchmark for blood
      culture contamination is 3%. Our aim with the quality improvement project was to
      reduce the contamination rate at our children's hospital from a mean of 2.85% to
      <1.5% in 2 years. METHODS: After initial unit-specific efforts, we formed a
      multidisciplinary team, created a process map and a cause-and-effect analysis,
      sent out surveys to nurses, and created observation sheets used to identify
      problem areas and record the most common deviations during the collection
      process. We also standardized the blood culture collection protocol and
      reemphasized nurse education in person and with online modules. During our
      project, we noted that nurses were collecting 1 to 3 mL of blood on all children
      regardless of weight. We developed optimal weight-based blood volumes and, after
      educating ordering providers, we updated our electronic medical record to reflect
      appropriate volumes in the order. RESULTS: Despite a steady increase in the
      number of blood cultures collected at our children's hospital, we were able to
      decrease the average contamination rate from 2.85% to 1.54%, saving the hospital
      an estimated average of $49 998 per month. CONCLUSIONS: By standardizing blood
      culture collection methods, optimizing blood volume, creating checklists, and
      reinforcing nurse education, we were able to develop a best practice for
      pediatric blood culture collection and reduce blood culture contamination to a
      sustainable low rate at our children's hospital.

PMID- 30217807
TI  - Genetic Variants Associated with Circulating Fibroblast Growth Factor 23.
AB  - BACKGROUND: Fibroblast growth factor 23 (FGF23), a bone-derived hormone that
      regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of
      mineral and bone disorders in CKD and is an emerging cardiovascular risk factor.
      Central elements of FGF23 regulation remain incompletely understood; genetic
      variation may help explain interindividual differences. METHODS: We performed a
      meta-analysis of genome-wide association studies of circulating FGF23
      concentrations among 16,624 participants of European ancestry from seven cohort
      studies, excluding participants with eGFR<30 ml/min per 1.73 m2 to focus on FGF23
      under normal conditions. We evaluated the association of single-nucleotide
      polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted
      for age, sex, study site, and principal components of ancestry. A second model
      additionally adjusted for BMI and eGFR. RESULTS: We discovered 154 SNPs from five
      independent regions associated with FGF23 concentration. The SNP with the
      strongest association, rs17216707 (P=3.0*10-24), lies upstream of CYP24A1, which
      encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25
      hydroxyvitamin D. Each additional copy of the T allele at this locus is
      associated with 5% higher FGF23 concentration. Another locus strongly associated
      with variations in FGF23 concentration is rs11741640, within RGS14 and upstream
      of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment
      for BMI and eGFR did not materially alter the magnitude of these associations.
      Another top locus (within ABO, the ABO blood group transferase gene) was no
      longer statistically significant at the genome-wide level. CONCLUSIONS: Common
      genetic variants located near genes involved in vitamin D metabolism and renal
      phosphate transport are associated with differences in circulating FGF23
      concentrations.

PMID- 30217809
TI  - The LPA-LPA4 axis is required for establishment of bipolar morphology and radial
      migration of newborn cortical neurons.
AB  - Newborn neurons in the developing neocortex undergo radial migration, a process
      that is coupled with their precise passage from multipolar to bipolar shape. The
      cell-extrinsic signals that govern this transition are, however, poorly
      understood. Here, we find that lysophosphatidic acid (LPA) signaling contributes
      to the establishment of a bipolar shape in mouse migratory neurons through LPA
      receptor 4 (LPA4). LPA4 is robustly expressed in migratory neurons. LPA4-depleted
      neurons show impaired multipolar-to-bipolar transition and become arrested in
      their migration. Further, LPA4-mediated LPA signaling promotes formation of the
      pia-directed process in primary neurons overlaid on neocortical slices. In
      addition, LPA4 depletion is coupled with altered actin organization as well as
      with destabilization of the F-actin-binding protein filamin A (FlnA). Finally,
      overexpression of FlnA rescues the morphology and migration defects of LPA4
      depleted neurons. Thus, the LPA-LPA4 axis regulates bipolar morphogenesis and
      radial migration of newborn cortical neurons via remodeling of the actin
      cytoskeleton.

PMID- 30217810
TI  - Clonal analysis reveals laminar fate multipotency and daughter cell apoptosis of
      mouse cortical intermediate progenitors.
AB  - In developing cerebral cortex, most pyramidal-projection neurons are produced by
      intermediate progenitors (IPs), derived in turn from radial glial progenitors.
      Although IPs produce neurons for all cortical layers, it is unknown whether
      individual IPs produce multiple or single laminar fates, and the potential of IPs
      for extended proliferation remains uncertain. Previously, we found that, at the
      population level, early IPs (present during lower-layer neurogenesis) produce
      lower- and upper-layer neurons, whereas late IPs produce upper-layer neurons
      only. Here, we employed mosaic analysis with double markers (MADM) in mice to
      sparsely label early IP clones. Most early IPs produced 1-2 neurons for deep
      layers only. Less frequently, early IPs produced larger clones (up to 12 neurons)
      spanning lower and upper layers, or upper layers only. The majority of IP-derived
      clones (~66%) were associated with asymmetric cell death after the first
      division. These data demonstrate that laminar fate is not predetermined, at least
      in some IPs. Rather, the heterogeneous sizes and laminar fates of early IP clones
      are correlated with cell division/death/differentiation choices and neuron
      birthdays, respectively.

PMID- 30217811
TI  - Molecular diversification of regulatory T cells in nonlymphoid tissues.
AB  - Foxp3+CD4+ regulatory T cells (Tregs) accumulate in certain nonlymphoid tissues,
      where they control diverse aspects of organ homeostasis. Populations of tissue
      Tregs, as they have been termed, have transcriptomes distinct from those of their
      counterparts in lymphoid organs and other nonlymphoid tissues. We examined the
      diversification of Tregs in visceral adipose tissue, skeletal muscle, and the
      colon vis-a-vis lymphoid organs from the same individuals. The unique
      transcriptomes of the various tissue Treg populations resulted from layering of
      tissue-restricted open chromatin regions over regions already open in the spleen,
      the latter tagged by super-enhancers and particular histone marks. The binding
      motifs for a small number of transcription factor (TF) families were repeatedly
      enriched within the accessible chromatin stretches of Tregs in the three
      nonlymphoid tissues. However, a bioinformatically and experimentally validated
      transcriptional network, constructed by integrating chromatin accessibility and
      single-cell transcriptomic data, predicted reliance on different TF family
      members in the different tissues. The network analysis also revealed that tissue
      restricted and broadly acting TFs were integrated into feed-forward loops to
      enforce tissue-specific gene expression in nonlymphoid-tissue Tregs. Overall,
      this study provides a framework for understanding the epigenetic dynamics of T
      cells operating in nonlymphoid tissues, which should inform strategies for
      specifically targeting them.

PMID- 30217812
TI  - A FRESH approach: Combining basic science and social good.
AB  - A program to study HIV infection is empowering African women.

PMID- 30217813
TI  - Structural and spectroscopic analyses of the sporulation killing factor
      biosynthetic enzyme SkfB, a bacterial AdoMet radical sactisynthase.
AB  - Sactipeptides are a subclass of ribosomally synthesized and post-translationally
      modified peptides (RiPPs). They contain a unique thioether bond, referred to as a
      sactionine linkage, between the sulfur atom of a cysteine residue and the alpha
      carbon of an acceptor residue. These linkages are formed via radical chemistry
      and are essential for the spermicidal, antifungal, and antibacterial properties
      of sactipeptides. Enzymes that form these linkages, called sactisynthases, are
      AdoMet radical enzymes in the SPASM/Twitch subgroup whose structures are
      incompletely characterized. Here, we present the X-ray crystal structure to 1.29
      A resolution and Mossbauer analysis of SkfB, a sactisynthase from Bacillus
      subtilis involved in making sporulation killing factor (SKF). We found that SkfB
      is a modular enzyme with an N-terminal peptide-binding domain comprising a RiPP
      recognition element (RRE), a middle domain that forms a classic AdoMet radical
      partial (beta/alpha)6 barrel structure and displays AdoMet bound to the [4Fe-4S]
      cluster, and a C-terminal region characteristic of the so-called Twitch domain
      housing an auxiliary iron-sulfur cluster. Notably, both crystallography and
      Mossbauer analyses suggest that SkfB can bind a [2Fe-2S] cluster at the auxiliary
      cluster site, which has been observed only once before in a SPASM/Twitch
      auxiliary cluster site in the structure of another AdoMet radical enzyme, the
      pyrroloquinoline quinone biosynthesis enzyme PqqE. Taken together, our findings
      indicate that SkfB from B. subtilis represents a unique enzyme containing several
      structural features observed in other AdoMet radical enzymes.

PMID- 30217814
TI  - In vivo cross-linking supports a head-to-tail mechanism for regulation of the
      plant plasma membrane P-type H+-ATPase.
AB  - In higher plants, a P-type proton-pumping ATPase generates the proton-motive
      force essential for the function of all other transporters and for proper growth
      and development. X-ray crystallographic studies of the plant plasma membrane
      proton pump have provided information on amino acids involved in ATP catalysis
      but provided no information on the structure of the C-terminal regulatory domain.
      Despite progress in elucidating enzymes involved in the signaling pathways that
      activate or inhibit this pump, the site of interaction of the C-terminal
      regulatory domain with the catalytic domains remains a mystery. Genetic studies
      have pointed to amino acids in various parts of the protein that may be involved,
      but direct chemical evidence for which ones are specifically interacting with the
      C terminus is lacking. In this study, we used in vivo cross-linking experiments
      with a photoreactive unnatural amino acid, p-benzoylphenylalanine, and tandem MS
      to obtain direct evidence that the C-terminal regulatory domain interacts with
      amino acids located within the N-terminal actuator domain. Our observations are
      consistent with a mechanism in which intermolecular, rather than intramolecular,
      interactions are involved. Our model invokes a "head-to-tail" organization of
      ATPase monomers in which the C-terminal domain of one ATPase molecule interacts
      with the actuator domain of another ATPase molecule. This model serves to explain
      why cross-linked peptides are found only in dimers and trimers, and it is
      consistent with prior studies suggesting that within the membrane the protein can
      be organized as homopolymers, including dimers, trimers, and hexamers.

PMID- 30217815
TI  - Endogenous insertion of non-native metalloporphyrins into human membrane
      cytochrome P450 enzymes.
AB  - Human cytochrome P450 enzymes are membrane-bound heme-containing monooxygenases.
      As is the case for many heme-containing enzymes, substitution of the metal in the
      center of the heme can be useful for mechanistic and structural studies of P450
      enzymes. For many heme proteins, the iron protoporphyrin prosthetic group can be
      extracted and replaced with protoporphyrin containing another metal, but human
      membrane P450 enzymes are not stable enough for this approach. The method
      reported herein was developed to endogenously produce human membrane P450
      proteins with a nonnative metal in the heme. This approach involved coexpression
      of the P450 of interest, a heme uptake system, and a chaperone in Escherichia
      coli growing in iron-depleted minimal medium supplemented with the desired trans
      metallated protoporphyrin. Using the steroidogenic P450 enzymes CYP17A1 and
      CYP21A2 and the drug-metabolizing CYP3A4, we demonstrate that this approach can
      be used with several human P450 enzymes and several different metals, resulting
      in fully folded proteins appropriate for mechanistic, functional, and structural
      studies including solution NMR.

PMID- 30217816
TI  - Insulin-like growth factor-1 acts as a zeitgeber on hypothalamic circadian clock
      gene expression via glycogen synthase kinase-3beta signaling.
AB  - Brain and muscle ARNT-like protein-1 (BMAL-1) is an important component of the
      cellular circadian clock. Proteins such as epidermal (EGF) or nerve growth factor
      (NGF) affect the cellular clock via extracellular signal-regulated kinases-1/2
      (ERK-1/2) in NIH3T3 or neuronal stem cells, but no such data are available for
      the insulin-like growth factor-1 (IGF-1). The hypothalamus expresses receptors
      for all three growth factors, acts as a central circadian pacemaker, and releases
      hormones in a circadian fashion. However, little is known about growth factor
      induced modulation of clock gene activity in hypothalamic cells. Here, we
      investigated effects of IGF-1, EGF, or NGF on the Bmal-1 promoter in two
      hypothalamic cell lines. We found that only IGF-1 but not EGF or NGF enhanced
      activity of the Bmal-1 promoter. Inhibition of ERK-1/2 activity did not affect
      IGF-1-induced Bmal-1 promoter activation and all three growth factors similarly
      phosphorylated ERK-1/2, questioning a role for ERK-1/2 in controlling BMAL-1
      promoter activity. Of note, only IGF-1 induced sustained phosphorylation of
      glycogen synthase kinase-3beta (GSK-3beta). Moreover, the GSK-3beta inhibitor
      lithium or siRNA-mediated GSK-3beta knockdown diminished the effects of IGF-1 on
      the Bmal-1 promoter. When IGF-1 was used in the context of temperature cycles
      entraining hypothalamic clock gene expression to a 24-h rhythm, it shifted the
      phase of Bmal-1 promoter activity, indicating that IGF-1 functions as a zeitgeber
      for cellular hypothalamic circadian clocks. Our results reveal that IGF-1
      regulates clock gene expression and that GSK-3beta but not ERK-1/2 is required
      for the IGF-1-mediated regulation of the Bmal-1 promoter in hypothalamic cells.

PMID- 30217817
TI  - Fibroblast growth factor receptor 5 (FGFR5) is a co-receptor for FGFR1 that is up
      regulated in beta-cells by cytokine-induced inflammation.
AB  - Fibroblast growth factor receptor-1 (FGFR1) activity at the plasma membrane is
      tightly controlled by the availability of co-receptors and competing receptor
      isoforms. We have previously shown that FGFR1 activity in pancreatic beta-cells
      modulates a wide range of processes, including lipid metabolism, insulin
      processing, and cell survival. More recently, we have revealed that co-expression
      of FGFR5, a receptor isoform that lacks a tyrosine-kinase domain, influences
      FGFR1 responses. We therefore hypothesized that FGFR5 is a co-receptor to FGFR1
      that modulates responses to ligands by forming a receptor heterocomplex with
      FGFR1. We first show here increased FGFR5 expression in the pancreatic islets of
      nonobese diabetic (NOD) mice and also in mouse and human islets treated with
      proinflammatory cytokines. Using siRNA knockdown, we further report that FGFR5
      and FGFR1 expression improves beta-cell survival. Co-immunoprecipitation and
      quantitative live-cell imaging to measure the molecular interaction between FGFR5
      and FGFR1 revealed that FGFR5 forms a mixture of ligand-independent homodimers
      (~25%) and homotrimers (~75%) at the plasma membrane. Interestingly, co-expressed
      FGFR5 and FGFR1 formed heterocomplexes with a 2:1 ratio and subsequently
      responded to FGF2 by forming FGFR5/FGFR1 signaling complexes with a 4:2 ratio.
      Taken together, our findings identify FGFR5 as a co-receptor that is up-regulated
      by inflammation and promotes FGFR1-induced survival, insights that reveal a
      potential target for intervention during beta-cell pathogenesis.

PMID- 30217818
TI  - Phosphatase activity of small C-terminal domain phosphatase 1 (SCP1) controls the
      stability of the key neuronal regulator RE1-silencing transcription factor
      (REST).
AB  - The RE1-silencing transcription factor (REST) is the major scaffold protein for
      assembly of neuronal gene silencing complexes that suppress gene transcription
      through regulating the surrounding chromatin structure. REST represses neuronal
      gene expression in stem cells and non-neuronal cells, but it is minimally
      expressed in neuronal cells to ensure proper neuronal development. Dysregulation
      of REST function has been implicated in several cancers and neurological
      diseases. Modulating REST gene silencing is challenging because cellular and
      developmental differences can affect its activity. We therefore considered the
      possibility of modulating REST activity through its regulatory proteins. The
      human small C-terminal domain phosphatase 1 (SCP1) regulates the phosphorylation
      state of REST at sites that function as REST degradation checkpoints. Using
      kinetic analysis and direct visualization with X-ray crystallography, we show
      that SCP1 dephosphorylates two degron phosphosites of REST with a clear
      preference for phosphoserine 861 (pSer-861). Furthermore, we show that SCP1
      stabilizes REST protein levels, which sustains REST's gene silencing function in
      HEK293 cells. In summary, our findings strongly suggest that REST is a bona fide
      substrate for SCP1 in vivo and that SCP1 phosphatase activity protects REST
      against degradation. These observations indicate that targeting REST via its
      regulatory protein SCP1 can modulate its activity and alter signaling in this
      essential developmental pathway.

PMID- 30217819
TI  - Impact of 17beta-estradiol on complex I kinetics and H2O2 production in liver and
      skeletal muscle mitochondria.
AB  - Naturally or surgically induced postmenopausal women are widely prescribed
      estrogen therapies to alleviate symptoms associated with estrogen loss and to
      lower the subsequent risk of developing metabolic diseases, including diabetes
      and nonalcoholic fatty liver disease. However, the molecular mechanisms by which
      estrogens modulate metabolism across tissues remain ill-defined. We have
      previously reported that 17beta-estradiol (E2) exerts antidiabetogenic effects in
      ovariectomized (OVX) mice by protecting mitochondrial and cellular redox function
      in skeletal muscle. The liver is another key tissue for glucose homeostasis and a
      target of E2 therapy. Thus, in the present study we determined the effects of
      acute loss of ovarian E2 and E2 administration on liver mitochondria. In contrast
      to skeletal muscle mitochondria, E2 depletion via OVX did not alter liver
      mitochondrial respiratory function or complex I (CI) specific activities (NADH
      oxidation, quinone reduction, and H2O2 production). Surprisingly, in vivo E2
      replacement therapy and in vitro E2 exposure induced tissue-specific effects on
      both CI activity and on the rate and topology of CI H2O2 production. Overall, E2
      therapy protected and restored the OVX-induced reduction in CI activity in
      skeletal muscle, whereas in liver mitochondria E2 increased CI H2O2 production
      and decreased ADP-stimulated respiratory capacity. These results offer novel
      insights into the tissue-specific effects of E2 on mitochondrial function.

PMID- 30217820
TI  - Structural and functional characterization of IdiA/FutA (Tery_3377), an iron
      binding protein from the ocean diazotroph Trichodesmium erythraeum.
AB  - Atmospheric nitrogen fixation by photosynthetic cyanobacteria (diazotrophs)
      strongly influences oceanic primary production and in turn affects global
      biogeochemical cycles. Species of the genus Trichodesmium are major contributors
      to marine diazotrophy, accounting for a significant proportion of the fixed
      nitrogen in tropical and subtropical oceans. However, Trichodesmium spp. are
      metabolically constrained by the availability of iron, an essential element for
      both the photosynthetic apparatus and the nitrogenase enzyme. Survival strategies
      in low-iron environments are typically poorly characterized at the molecular
      level, because these bacteria are recalcitrant to genetic manipulation. Here, we
      studied a homolog of the iron deficiency-induced A (IdiA)/ferric uptake
      transporter A (FutA) protein, Tery_3377, which has been used as an in situ iron
      stress biomarker. IdiA/FutA has an ambiguous function in cyanobacteria, with its
      homologs hypothesized to be involved in distinct processes depending on their
      cellular localization. Using signal sequence fusions to GFP and heterologous
      expression in the model cyanobacterium Synechocystis sp. PCC 6803, we show that
      Tery_3377 is targeted to the periplasm by the twin-arginine translocase and can
      complement the deletion of the native Synechocystis ferric-iron ABC transporter
      periplasmic binding protein (FutA2). EPR spectroscopy revealed that purified
      recombinant Tery_3377 has specificity for iron in the Fe3+ state, and an X-ray
      crystallography-determined structure uncovered a functional iron substrate
      binding domain, with Fe3+ pentacoordinated by protein and buffer ligands. Our
      results support assignment of Tery_3377 as a functional FutA subunit of an Fe3+
      ABC transporter but do not rule out dual IdiA function.

PMID- 30217821
TI  - Molecular architecture of G-quadruplex structures generated on duplex Rif1
      binding sequences.
AB  - G-quadruplexes (G4s) are four-stranded DNA structures comprising stacks of four
      guanines, are prevalent in genomes, and have diverse biological functions in
      various chromosomal structures. A conserved protein, Rap1-interacting factor 1
      (Rif1) from fission yeast (Schizosaccharomyces pombe), binds to Rif1-binding
      sequence (Rif1BS) and regulates DNA replication timing. Rif1BS is characterized
      by the presence of multiple G-tracts, often on both strands, and their unusual
      spacing. Although previous studies have suggested generation of G4-like
      structures on duplex Rif1BS, its precise molecular architecture remains unknown.
      Using gel-shift DNA binding assays and DNA footprinting with various nuclease
      probes, we show here that both of the Rif1BS strands adopt specific higher-order
      structures upon heat denaturation. We observed that the structure generated on
      the G-strand is consistent with a G4 having unusually long loop segments and that
      the structure on the complementary C-strand does not have an intercalated motif
      (i-motif). Instead, we found that the formation of the C-strand structure depends
      on the G4 formation on the G-strand. Thus, the higher-order structure generated
      at Rif1BS involved both DNA strands, and in some cases, G4s may form on both of
      these strands. The presence of multiple G-tracts permitted the formation of
      alternative structures when some G-tracts were mutated or disrupted by
      deazaguanine replacement, indicating the robust nature of DNA higher-order
      structures generated at Rif1BS. Our results provide general insights into DNA
      structures generated at G4-forming sequences on duplex DNA.

PMID- 30217822
TI  - Two distinct conformations of factor H regulate discrete complement-binding
      functions in the fluid phase and at cell surfaces.
AB  - Factor H (FH) is the major regulator of C3b in the alternative pathway of the
      complement system in immunity. FH comprises 20 short complement regulator (SCR)
      domains, including eight glycans, and its Y402H polymorphism predisposes those
      who carry it to age-related macular degeneration. To better understand FH
      complement binding and self-association, we have studied the solution structures
      of both the His-402 and Tyr-402 FH allotypes. Analytical ultracentrifugation
      revealed that up to 12% of both FH allotypes self-associate, and this was
      confirmed by small-angle X-ray scattering (SAXS), MS, and surface plasmon
      resonance analyses. SAXS showed that monomeric FH has a radius of gyration (Rg )
      of 7.2-7.8 nm and a length of 25 nm. Starting from known structures for the SCR
      domains and glycans, the SAXS data were fitted using Monte Carlo methods to
      determine atomistic structures of monomeric FH. The analysis of 29,715 physically
      realistic but randomized FH conformations resulted in 100 similar best-fit FH
      structures for each allotype. Two distinct molecular structures resulted that
      showed either an extended N-terminal domain arrangement with a folded-back C
      terminus or an extended C terminus and a folded-back N terminus. These two
      structures are the most accurate to date for glycosylated full-length FH. To
      clarify FH functional roles in host protection, crystal structures for the FH
      complexes with C3b and C3dg revealed that the extended N-terminal conformation
      accounted for C3b fluid-phase regulation, the extended C-terminal conformation
      accounted for C3d binding, and both conformations accounted for bivalent FH
      binding to glycosaminoglycans on the target cell surface.

PMID- 30217823
TI  - InhA, the enoyl-thioester reductase from Mycobacterium tuberculosis forms a
      covalent adduct during catalysis.
AB  - The enoyl-thioester reductase InhA catalyzes an essential step in fatty acid
      biosynthesis of Mycobacterium tuberculosis and is a key target of
      antituberculosis drugs to combat multidrug-resistant M. tuberculosis strains.
      This has prompted intense interest in the mechanism and intermediates of the InhA
      reaction. Here, using enzyme mutagenesis, NMR, stopped-flow spectroscopy, and LC
      MS, we found that the NADH cofactor and the CoA thioester substrate form a
      covalent adduct during the InhA catalytic cycle. We used the isolated adduct as a
      molecular probe to directly access the second half-reaction of the catalytic
      cycle of InhA (i.e. the proton transfer), independently of the first half
      reaction (i.e. the initial hydride transfer) and to assign functions to two
      conserved active-site residues, Tyr-158 and Thr-196. We found that Tyr-158 is
      required for the stereospecificity of protonation and that Thr-196 is partially
      involved in hydride transfer and protonation. The natural tendency of InhA to
      form a covalent C2-ene adduct calls for a careful reconsideration of the enzyme's
      reaction mechanism. It also provides the basis for the development of effective
      tools to study, manipulate, and inhibit the catalytic cycle of InhA and related
      enzymes of the short-chain dehydrogenase/reductase (SDR) superfamily. In summary,
      our work has uncovered the formation of a covalent adduct during the InhA
      catalytic cycle and identified critical residues required for catalysis,
      providing further insights into the InhA reaction mechanism important for the
      development of antituberculosis drugs.

PMID- 30217824
TI  - c-Jun N-terminal kinase (JNK)-mediated induction of mSin1 expression and mTORC2
      activation in mesenchymal cells during fibrosis.
AB  - Mammalian target of rapamycin complex 2 (mTORC2) has been shown to regulate
      mTORC1/4E-BP1/eIF4E signaling and collagen I expression in mesenchymal cells
      (MCs) during fibrotic activation. Here we investigated the regulation of the
      mTORC2 binding partner mammalian stress-activated protein kinase-interacting
      protein 1 (mSin1) in MCs derived from human lung allografts and identified a
      novel role for mSin1 during fibrosis. mSin1 was identified as a common downstream
      target of key fibrotic pathways, and its expression was increased in MCs in
      response to pro-fibrotic mediators: lysophosphatidic acid (LPA), transforming
      growth factor beta, and interleukin 13. Fibrotic MCs had higher mSin1 protein
      levels than nonfibrotic MCs, and siRNA-mediated silencing of mSIN1 inhibited
      collagen I expression and mTORC1/2 activity in these cells. Autocrine LPA
      signaling contributed to constitutive up-regulation of mSin1 in fibrotic MCs, and
      mSin1 was decreased because of LPA receptor 1 siRNA treatment. We identified c
      Jun N-terminal kinase (JNK) as a key intermediary in mSin1 up-regulation by the
      pro-fibrotic mediators, as pharmacological and siRNA-mediated inhibition of JNK
      prevented the LPA-induced mSin1 increase. Proteasomal inhibition rescued mSin1
      levels after JNK inhibition in LPA-treated MCs, and the decrease in mSin1
      ubiquitination in response to LPA was counteracted by JNK inhibitors.
      Constitutive JNK1 overexpression induced mSin1 expression and could drive mTORC2
      and mTORC1 activation and collagen I expression in nonfibrotic MCs, effects that
      were reversed by siRNA-mediated mSIN1 silencing. These results indicate that LPA
      stabilizes mSin1 protein expression via JNK signaling by blocking its proteasomal
      degradation and identify the LPA/JNK/mSin1/mTORC/collagen I pathway as critical
      for fibrotic activation of MCs.

PMID- 30217826
TI  - Comparison of Micropore Distribution in Cell Walls of Softwood and Hardwood
      Xylem.
AB  - The porosity of wood cell walls is of interest for both understanding xylem
      functionality and from a wood materials perspective. The movement of water in
      xylem generally occurs through the macroporous networks formed in softwood by
      bordered pits and in hardwood by the intervessel pits and open conduits created
      by vessels and perforation plates. In some situations, such as cavitated xylem,
      water can only move through the micropores that occur in lignified tracheid and
      fiber cell walls; however, these micropore networks are poorly understood. Here,
      we used molecular microscopy analysis of radiata pine (Pinus radiata) and red
      beech (Nothofagus fusca) to determine the distribution of micropores in the
      secondary walls and middle lamellae of tracheids and fibers in relation to cell
      wall composition. Using two different types of probe, we identified a greater
      porosity of secondary cell walls and a reduced porosity of the middle lamella.
      Areas of reduced porosity were observed in the outer regions of the secondary
      cell wall of both tracheids and fibers that appear unrelated to lignification or
      the distribution of cellulose, mannan, and xylan. Hardwood fiber cell walls were
      less lignified than those of softwood tracheids and showed greater accessibility
      to porosity probes. Vessel cell walls were comparable to those of fibers in terms
      of both porosity and lignification. Lignification is probably the primary
      determinant of cell wall porosity in xylem. The highly lignified middle lamella,
      and lumen surface, act as a barrier to probe movement and, therefore, water
      movement in both softwood and hardwood.

PMID- 30217825
TI  - Human T-cell leukemia virus type 1 Gag domains have distinct RNA-binding
      specificities with implications for RNA packaging and dimerization.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus that has
      conclusively been shown to cause human diseases. In HIV-1, specific interactions
      between the nucleocapsid (NC) domain of the Gag protein and genomic RNA (gRNA)
      mediate gRNA dimerization and selective packaging; however, the mechanism for
      gRNA packaging in HTLV-1, a deltaretrovirus, is unclear. In other
      deltaretroviruses, the matrix (MA) and NC domains of Gag are both involved in
      gRNA packaging, but MA binds nucleic acids with higher affinity and has more
      robust chaperone activity, suggesting that this domain may play a primary role.
      Here, we show that the MA domain of HTLV-1, but not the NC domain, binds short
      hairpin RNAs derived from the putative gRNA packaging signal. RNA probing of the
      HTLV-1 5' leader and cross-linking studies revealed that the primer-binding site
      and a region within the putative packaging signal form stable hairpins that
      interact with MA. In addition to a previously identified palindromic dimerization
      initiation site (DIS), we identified a new DIS in HTLV-1 gRNA and found that both
      palindromic sequences bind specifically the NC domain. Surprisingly, a mutant
      partially defective in dimer formation in vitro exhibited a significant increase
      in RNA packaging into HTLV-1-like particles, suggesting that efficient RNA
      dimerization may not be strictly required for RNA packaging in HTLV-1. Moreover,
      the lifecycle of HTLV-1 and other deltaretroviruses may be characterized by NC
      and MA functions that are distinct from those of the corresponding HIV-1
      proteins, but together provide the functions required for viral replication.

PMID- 30217827
TI  - VAMP711 Is Required for Abscisic Acid-Mediated Inhibition of Plasma Membrane H+
      ATPase Activity.
AB  - Drought stress is a limiting environmental factor that affects plant growth and
      development. The plant hormone abscisic acid (ABA) plays an important role in
      plant drought responses. Previous studies have indicated that ABA inhibits plasma
      membrane H+-ATPase (PM H+-ATPase) activity, and the decrease in PM H+-ATPase
      activity promotes stomatal closure under drought stress, thereby reducing water
      loss. However, the underlying molecular mechanisms are not well understood. In
      this study, we found that in Arabidopsis (Arabidopsis thaliana), ABA induces an N
      ethylmaleimide-sensitive factor attachment protein receptor protein, namely,
      VESICLE-ASSOCIATED MEMBRANE PROTEIN 711 (VAMP711), to interact with the
      Arabidopsis PM H+-ATPases AHA1 and AHA2. The interaction occurs at their C
      termini and inhibits PM H+-ATPase activity. Deletion of VAMP711 in Arabidopsis
      results in a higher PM H+-ATPase activity and slower stomatal closure in response
      to ABA and drought treatments. In addition, overexpression of VAMP711 partially
      rescues the drought-sensitive phenotype of ost2-2D, a mutation in AHA1 resulting
      in a constitutive activated PM H+-ATPase. Our results demonstrate that VAMP711 is
      involved in regulating ABA-mediated inhibition of PM H+-ATPase activity and
      stomatal closure in response to drought stress.

PMID- 30217828
TI  - Correction: Cross-Presentation of Soluble and Cell-Associated Antigen by Murine
      Hepatocytes Is Enhanced by Collectrin Expression.

PMID- 30217829
TI  - Observed Antibody Space: A Resource for Data Mining Next-Generation Sequencing of
      Antibody Repertoires.
AB  - Abs are immune system proteins that recognize noxious molecules for elimination.
      Their sequence diversity and binding versatility have made Abs the primary class
      of biopharmaceuticals. Recently, it has become possible to query their immense
      natural diversity using next-generation sequencing of Ig gene repertoires (Ig
      seq). However, Ig-seq outputs are currently fragmented across repositories and
      tend to be presented as raw nucleotide reads, which means nontrivial effort is
      required to reuse the data for analysis. To address this issue, we have collected
      Ig-seq outputs from 55 studies, covering more than half a billion Ab sequences
      across diverse immune states, organisms (primarily human and mouse), and
      individuals. We have sorted, cleaned, annotated, translated, and numbered these
      sequences and make the data available via our Observed Antibody Space (OAS)
      resource at http://antibodymap.org The data within OAS will be regularly updated
      with newly released Ig-seq datasets. We believe OAS will facilitate data mining
      of immune repertoires for improved understanding of the immune system and
      development of better biotherapeutics.

PMID- 30217830
TI  - Neutrophil Vaccination Dynamics and Their Capacity To Mediate B Cell Help in
      Rhesus Macaques.
AB  - Neutrophils are the most abundant leukocyte and play a critical role in the
      initial response to an Ag. Recently, their ability to contribute to adaptive
      immunity has been highlighted. We evaluated the ability of neutrophils from blood
      to contribute to the adaptive immune response in a preclinical rhesus macaque SIV
      vaccine trial. Replication-competent adenovirus-SIV recombinants induced
      neutrophil activation, B cell help markers, and enhanced ability to generate
      reactive oxygen species. Boosting with SIV vaccines (adjuvant together with ALVAC
      or DNA plus envelope protein) elicited significant neutrophil responses. Serum
      cytokine and chemokine levels induced correlated with the frequency of neutrophil
      subsets expressing IL-21, myeloperoxidase, and CD64. Post-SIV infection,
      neutrophils exhibited dysfunction, both phenotypically and functionally. B cells
      from protected and infected macaques cocultured with autologous polymorphonuclear
      cells, consisting primarily of neutrophils, were activated, underwent class
      switching, and produced Abs. This B cell help was not aided by addition of IL-10
      and was largely contact dependent. Numerous genes associated with inflammation,
      Ab production, and chemotaxis were upregulated in the cocultured B cells. We
      conclude that immune stimulation by vaccination or antigenic exposure imparts a
      greater ability of neutrophils to contribute to the adaptive immune response.
      Harnessing this granulocytic response has the potential to improve vaccine
      efficacy.

PMID- 30217831
TI  - Effects of training and competition on the sleep of elite athletes: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: To characterise the sleep of elite athletes and to identify factors
      associated with training and competition that negatively affect sleep. DESIGN:
      Prognosis systematic review. DATA SOURCES: Three databases (PubMed, SCOPUS and
      SPORTDiscus) were searched from inception to 26 February 2018. ELIGIBILITY
      CRITERIA FOR SELECTING STUDIES: Included studies objectively reported total sleep
      time (TST) and/or sleep efficiency (SE) in elite athletes. Studies were required
      to be observational or to include an observational trial. RESULTS: Fifty-four
      studies were included. During training, many studies reported athletes were
      unable to achieve TST (n=23/41) and/or SE (n=16/37) recommendations. On the night
      of competition, most studies reported athletes were unable to achieve TST
      (n=14/18) and/or SE (n=10/16) recommendations. TST was shorter (60 min) the night
      of competition compared with previous nights. SE was lower (1%) the night of
      competition compared with the previous night. TST was shorter the night of night
      competition (start >=18:00; 80 min) and day competition (20 min) compared with
      the previous night. SE was lower (3%-4%) the night of night competition but
      unchanged the night of day competition compared with previous nights. Early
      morning training (start <07:00), increases in training load (>25%), late
      night/early morning travel departure times, eastward air travel and altitude
      ascent impaired sleep. CONCLUSION: Athletes were often unable to achieve sleep
      recommendations during training or competition periods. Sleep was impaired the
      night of competition compared with previous nights. Early morning training,
      increases in training load, travel departure times, jet lag and altitude can
      impair athletes' sleep. PROSPERO REGISTRATION NUMBER: CRD42017074367.

PMID- 30217832
TI  - Cardiovascular risk profile in Olympic athletes: an unexpected and underestimated
      risk scenario.
AB  - BACKGROUND: Prevalence of cardiovascular (CV) risk factors has been poorly
      explored in subjects regularly engaged in high-intensity exercise programmes. Our
      aim was, therefore, to assess the prevalence and distribution of CV risk factors
      in a large population of competitive athletes, to derive the characteristics of
      athlete's lifestyle associated with the best CV profile. METHODS: 1058 Olympic
      athletes (656 males, 402 females), consecutively evaluated in the period 2014
      2016, represent the study population. Prevalence and distribution of CV risk
      factors was assessed, in relation to age, body size and sport. FINDINGS:
      Dyslipidemia was the most common risk (32%), followed by increased waist
      circumference (25%), positive family history (18%), smoking habit (8%),
      hypertension (3.8%) and hyperglycaemia (0.3%). Large subset of athletes (418,
      40%) had none or 1 (414, 39%) risk factor, while only a few (39, 3.7%) had 3/4 CV
      risk factors. The group without risks largely comprised endurance athletes (34%).
      Ageing was associated with higher total and low-density lipoprotein cholesterol,
      triglycerides (p<0.001) and glycaemia (p=0.002) and lower high-density
      lipoprotein cholesterol. On multivariate logistic regression analysis, age, BMI
      and body fat were identified as independent predictors of increased CV risk.
      INTERPRETATION: Dyslipidemia and increased waist circumference are common in
      elite athletes (32% and 25%, respectively). A large proportion (40%) of athletes,
      mostly endurance, are totally free from risk factors. Only a minority (3%)
      presents a high CV risk, largely expression of lifestyle and related to
      modifiable CV risk factors.

PMID- 30217833
TI  - Controlled ecological evaluation of an implemented exercise-training programme to
      prevent lower limb injuries in sport: population-level trends in hospital-treated
      injuries.
AB  - OBJECTIVE: Exercise-training programmes have reduced lower limb injuries in
      trials, but their population-level effectiveness has not been reported in
      implementation trials. This study aimed to demonstrate that routinely collected
      hospital data can be used to evaluate population-level programme effectiveness.
      METHOD: A controlled ecological design was used to evaluate the effect of
      FootyFirst, an exercise-training programme, on the number of hospital-treated
      lower limb injuries sustained by males aged 16-50 years while participating in
      community-level Australian Football. FootyFirst was implemented with 'support'
      (FootyFirst+S) or 'without support' (FootyFirst+NS) in different geographic
      regions of Victoria, Australia: 22 clubs in region 1: FootyFirst+S in 2012/2013;
      25 clubs in region 2: FootyFirst+NS in 2012/2013; 31 clubs region 3: control in
      2012, FootyFirst+S in 2013. Interrupted time-series analysis compared injury
      counts across regions and against trends in the rest of Victoria. RESULTS: After
      1 year of FootyFirst+S, there was a non-statistically significant decline in the
      number of lower limb injuries in region 1 (2012) and region 3 (2013); this was
      not maintained after 2 years in region 1. Compared with before FootyFirst in 2006
      2011, injury count changes at the end of 2013 were: region 1: 20.0% reduction
      (after 2 years support); region 2: 21.5% increase (after 2 years without
      support); region 3: 21.8% increase (after first year no programme, second year
      programme with support); rest of Victoria: 12.6% increase. CONCLUSION: Ecological
      analyses using routinely collected hospital data show promise as the basis of
      population-level programme evaluation. The implementation and sustainability of
      sports injury prevention programmes at the population-level remains challenging.

PMID- 30217834
TI  - External validation of the accuracy of 'CLLflow score'.

PMID- 30217835
TI  - Regulatory networks governing methionine catabolism into volatile organic sulfur
      containing compounds in Clonostachys rosea.
AB  - Adaptation to environmental perturbations requires living systems to coordinately
      regulate signaling pathways, gene expression and metabolism. To better understand
      the mechanisms underlying adaptation, the regulatory nodes within networks must
      be elucidated. Here, ARO8-2, which encodes an aminotransferase; PDC, which
      encodes a decarboxylase; and STR3, which encodes a demethiolase, were identified
      as key genes involved in the catabolism of methionine (Met) in the mycoparasitic
      fungus Clonostachys rosea isolated from Tuber melanosporum ascocarps. Exogenous
      Met induced the transcription of ARO8-2 and PDC but repressed the transcription
      of STR3, which is controlled by the putative binding sites of MSN2 and GLN3
      responding to nitrogen catabolite repression. Met and its structural derivatives
      function as glutamine synthetase inhibitors, resulting in the downregulation of
      STR3 expression. The putative GLN3 binding site was necessary for STR3
      downregulation. In Saccharomyces cerevisiae, Met and its structural derivatives
      also triggered downregulation of demethiolase gene expression. Altogether, the
      results indicated that exogenous Met triggered nitrogen catabolite repression,
      which stimulated the Ehrlich pathway and negatively regulated the demethiolation
      pathway via the methionine sulfoximine-responsive regulatory pathway. This
      finding revealed the regulatory nodes within the networks controlling the
      catabolism of Met into volatile organic sulfur-containing compounds, thereby
      enhancing our understanding of adaptation.IMPORTANCE Methionine (Met) shuttles
      organic nitrogen and plays a central role in nitrogen metabolism. Exogenous Met
      strongly induces the expression of ARO8-2 and PDC, represses the expression of
      STR3 and generates volatile organic sulfur-containing compounds (VOSCs) via the
      Ehrlich and demethiolation pathways. In this study, we used genetic,
      bioinformatic and metabolite-based analyses to confirm that transcriptional
      control of the aminotransferase gene ARO8-2, the decarboxylase gene PDC and the
      demethiolase gene STR3 modulates Met catabolism into VOSCs. Importantly, we found
      that in addition to the Ehrlich pathway, the demethiolation pathway was also
      regulated by a nitrogen catabolite repression-sensitive regulatory pathway that
      controlled the transcription of genes required to catabolize poor nitrogen
      sources. This work significantly advances our understanding of nitrogen
      catabolite repression-sensitive transcriptional regulation of sulfur-containing
      amino acid catabolism and provides a basis for engineering Met catabolic pathways
      for the production of fuel and valuable flavor alcohols.

PMID- 30217836
TI  - Phosphodiesterase EdpX1 Promotes Xanthomonas oryzae pv. oryzae Virulence,
      Exopolysaccharide Production, and Biofilm Formation.
AB  - In Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice, there
      are over 20 genes encoding GGDEF, EAL, and HD-GYP domains, which are potentially
      involved in the metabolism of second messenger c-di-GMP. In this study, we
      focused on the characterization of an EAL domain protein, EdpX1. Deletion of the
      edpX1 gene resulted in a 2-fold increase in the intracellular c-di-GMP levels,
      which were restored to the wild-type levels in the complemented DeltaedpX1(pB
      edpX1) strain, demonstrating that EdpX1 is an active phosphodiesterase (PDE) in
      X. oryzae pv. oryzae. In addition, colorimetric assays further confirmed the PDE
      activity of EdpX1 by showing that the E153A mutation at the EAL motif strongly
      reduced its activity. Virulence assays on the leaves of susceptible rice showed
      that the DeltaedpX1 mutant was severely impaired in causing disease symptoms. In
      trans expression of wild-type edpX1, but not edpX1 E153A, was able to complement
      the weakened virulence phenotype. These results indicated that an active EAL
      domain is required for EdpX1 to regulate the virulence of X. oryzae pv. oryzae.
      We then demonstrated that the DeltaedpX1 mutant was defective in secreting
      exopolysaccharide (EPS) and forming biofilms. The expression of edpX1 in the
      DeltaedpX1 mutant, but not edpX1 E153A, restored the defective phenotypes to near
      wild-type levels. In addition, we observed that EdpX1-green fluorescent protein
      (EdpX1-GFP) exhibited multiple subcellular localization foci, and this pattern
      was dependent on its transmembrane (TM) region, which did not seem to directly
      contribute to the regulatory function of EdpX1. Thus, we concluded that EdpX1
      exhibits PDE activity to control c-di-GMP levels, and its EAL domain is necessary
      and sufficient for its regulation of virulence in X. oryzae pv. oryzae.IMPORTANCE
      Bacteria utilize c-di-GMP as a second messenger to regulate various biological
      functions. The synthesis and degradation of c-di-GMP are catalyzed by GGDEF
      domains and an EAL or HD-GYP domain, respectively. Multiple genes encoding these
      domains are often found in one bacterial strain. For example, in the genome of X.
      oryzae pv. oryzae PXO99A, 26 genes encoding proteins containing these domains
      were identified. Therefore, to fully appreciate the complexity and specificity of
      c-di-GMP signaling in X. oryzae pv. oryzae, the enzymatic activities and
      regulatory functions of each GGDEF, EAL, and HD-GYP domain protein need to be
      elucidated. In this study, we showed that the EAL domain protein EdpX1 is a major
      PDE to regulate diverse virulence phenotypes through the c-di-GMP signaling
      pathway.

PMID- 30217837
TI  - Stress Resistance Development and Genome-Wide Transcriptional Response of
      Escherichia coli O157:H7 Adapted to Sublethal Thymol, Carvacrol, and trans
      Cinnamaldehyde.
AB  - Thymol, carvacrol, and trans-cinnamaldehyde are essential oil (EO) compounds with
      broad-spectrum antimicrobial activities against foodborne pathogens, including
      Escherichia coli O157:H7. However, little is known regarding direct resistance
      and cross-resistance development in E. coli O157:H7 after adaptation to sublethal
      levels of these compounds, and information is scarce on microbial adaptive
      responses at a molecular level. The present study demonstrated that E. coli
      O157:H7 was able to grow in the presence of sublethal thymol (1/2T), carvacrol
      (1/2C), or trans-cinnamaldehyde (1/2TC), displaying an extended lag phase
      duration and a lower maximum growth rate. EO-adapted cells developed direct
      resistance against lethal EO treatments and cross-resistance against heat (58
      degrees C) and oxidative (50 mM H2O2) stresses. However, no induction of acid
      resistance (simulated gastric fluid, pH 1.5) was observed. RNA sequencing
      revealed a large number (310 to 338) of differentially expressed (adjusted P
      value [Padj ], <0.05; fold change, >=5) genes in 1/2T and 1/2C cells, while 1/2TC
      cells only showed 27 genes with altered expression. In accordance with resistance
      phenotypes, the genes related to membrane, heat, and oxidative stress responses
      and genes related to iron uptake and metabolism were upregulated. Conversely,
      virulence genes associated with motility, biofilm formation, and efflux pumps
      were repressed. This study demonstrated the development of direct resistance and
      cross-resistance and characterized whole-genome transcriptional responses in E.
      coli O157:H7 adapted to sublethal thymol, carvacrol, or trans-cinnamaldehyde. The
      data suggested that caution should be exercised when using EO compounds as food
      antimicrobials, due to the potential stress resistance development in E. coli
      O157:H7.IMPORTANCE The present study was designed to understand transcriptomic
      changes and the potential development of direct and cross-resistance in essential
      oil (EO)-adapted Escherichia coli O157:H7. The results demonstrated altered
      growth behaviors of E. coli O157:H7 during adaptation in sublethal thymol,
      carvacrol, and trans-cinnamaldehyde. Generally, EO-adapted bacteria showed
      enhanced resistance against subsequent lethal EO, heat, and oxidative stresses,
      with no induction of acid resistance in simulated gastric fluid. A transcriptomic
      analysis revealed the upregulation of related stress resistance genes and a
      downregulation of various virulence genes in EO-adapted cells. This study
      provides new insights into microbial EO adaptation behaviors and highlights the
      risk of resistance development in adapted bacteria.

PMID- 30217838
TI  - A PCR-Based Method for Distinguishing between Two Common Beehive Bacteria,
      Paenibacillus larvae and Brevibacillus laterosporus.
AB  - Paenibacillus larvae and Brevibacillus laterosporus are two bacteria that are
      members of the Paenibacillaceae family. Both are commonly found in beehives and
      have historically been difficult to distinguish from each other due to related
      genetic and phenotypic characteristics and a shared ecological niche. Here, we
      discuss the likely mischaracterization of three 16S rRNA sequences previously
      published as P. larvae and provide the phylogenetic evidence that supported the
      GenBank reassignment of the sequences as B. laterosporus We explore the issues
      that arise by using only 16S rRNA or other single-gene analyses to distinguish
      between these bacteria. We also present three sets of molecular markers, two sets
      that distinguish P. larvae from B. laterosporus and other closely related species
      within the Paenibacillus genus and a third set that distinguishes B. laterosporus
      from P. larvae and other closely related species within the Brevibacillus genus.
      These molecular markers provide a tool for proper identification of these oft
      mistaken species.IMPORTANCE 16S rRNA gene sequencing in bacteria has long been
      held as the gold standard for typing bacteria and, for the most part, is an
      excellent method of taxonomically identifying different bacterial species.
      However, the high level of 16S rRNA sequence similarity of some published strains
      of P. larvae and B. laterosporus, as well as possible horizontal gene transfer
      events within their shared ecological niche, complicates the use of 16S rRNA
      sequence as an effective molecular marker for differentiating these two species.
      Additionally, shared characteristics of these bacteria limit the effectiveness of
      using traditional phenotypic identification assays, such as the catalase test.
      The results from this study provide PCR methods to quickly differentiate between
      these two genera and will be useful when studying Brevibacillus, Paenibacillus,
      and other disease-relevant bacteria commonly found in beehives.

PMID- 30217839
TI  - Metabolic Interactions of a Chain Elongation Microbiome.
AB  - Carbon chain elongation (CCE), a reaction within the carboxylate platform that
      elongates short-chain to medium-chain carboxylates by mixed culture, has
      attracted worldwide interest. The present study provides insights into the
      microbial diversity and predictive microbial metabolic pathways of a mixed
      culture CCE microbiome on the basis of a comparative analysis of the metagenome
      and metatranscriptome. We found that the microbial structure of an acclimated
      chain elongation microbiome was a highly similar to that of the original
      inoculating biogas reactor culture; however, the metabolic activities were
      completely different, demonstrating the high stability of the microbial structure
      and flexibility of its functions. Additionally, the fatty acid biosynthesis (FAB)
      pathway, rather than the well-known reverse beta-oxidation (RBO) pathway for CCE,
      was more active and pivotal, though the FAB pathway had more steps and consumed
      more ATP, a phenomenon that has rarely been observed in previous CCE studies. A
      total of 91 draft genomes were reconstructed from the metagenomic reads, of which
      three were near completion (completeness, >97%) and were assigned to unknown
      strains of Methanolinea tarda, Bordetella avium, and Planctomycetaceae The last
      two strains are likely new-found active participators of CCE in the mixed
      culture. Finally, a conceptual framework of CCE, including both pathways and the
      potential participators, was proposed.IMPORTANCE Carbon chain elongation means
      the conversion of short-chain volatile fatty acids to medium-chain carboxylates,
      such as n-caproate and n-caprylate with electron donors under anaerobic
      condition. This bio-reaction can both expand the resource of valuable
      biochemicals and broaden the utilization of low-grade organic residues in a
      sustainable biorefinery context. Clostridium kluyveri is conventionally
      considered model microbe for carbon chain elongation which uses the reverse beta
      oxidation pathway. However, little is known about the detailed microbial
      structure and function of other abundant microorganism in a mixed culture (or
      open culture) of chain elongation. We conducted the comparative metagenomic and
      metatranscriptomic analysis of a chain elongation microbiome to throw light on
      the underlying functional microbes and alternative pathways.

PMID- 30217840
TI  - Transfer of Enteric Viruses Adenovirus and Coxsackievirus and Bacteriophage MS2
      from Liquid to Human Skin.
AB  - Indirect exposure to waterborne viruses increases the risk of infection,
      especially among children with frequent hand-to-mouth contacts. Here, we
      quantified the transfer of one bacteriophage (MS2) and two enteric viruses
      (adenovirus and coxsackievirus) from liquid to skin. MS2, a commonly used enteric
      virus surrogate, was used to compare virus transfer rates in a volunteer trial to
      those obtained using human cadaver skin and synthetic skin. MS2 transfer to
      volunteer skin was similar to transfer to cadaver skin but significantly
      different from transfer to synthetic skin. The transfer of MS2, adenovirus, and
      coxsackievirus to cadaver skin was modeled using measurements for viruses
      attaching to the skin (adsorbed) and viruses in liquid residual on skin
      (unadsorbed). We find virus transfer per surface area is a function of the
      concentration of virus in the liquid and the film thickness of liquid retained on
      the skin and is estimable using a linear model. Notably, the amount of MS2
      adsorbed on the skin was on average 5 times higher than the amount of adenovirus
      and 4 times higher than the amount of coxsackievirus. Quantification of
      pathogenic virus retention to skin would thus be overestimated using MS2
      adsorption data. This study provides models of virus transfer useful for risk
      assessments of water-related activities, demonstrates significant differences in
      the transfer of pathogenic virus and MS2, and suggests cadaver skin as an
      alternative testing system for studying interactions between viruses and
      skin.IMPORTANCE Enteric viruses (viruses that infect the gastrointestinal tract)
      are responsible for most water-transmitted diseases. They are shed in high
      concentrations in the feces of infected individuals, persist for an extended
      period of time in water, and are highly infective. Exposure to contaminated water
      directly (through ingestion) or indirectly (for example, through hand-water
      contacts followed by hand-to-mouth contacts) increases the risk of virus
      transmission. The work described herein provides a quantitative model for
      estimating human-pathogenic virus retention on skin following contact with
      contaminated water. The work will be important in refining the contribution of
      indirect transmission of virus to risks associated with water-related activities.

PMID- 30217841
TI  - Rapid, parallel identification of pathways for catabolism of lignin-derived
      aromatic compounds in Novosphingobium aromaticivorans.
AB  - Transposon mutagenesis is a powerful technique in microbial genetics for the
      identification of genes in uncharacterized pathways. Recently, the throughput of
      transposon mutagenesis techniques has been dramatically increased through the
      combination of DNA barcoding and high-throughput sequencing. Here we show that,
      when applied to catabolic pathways, barcoded transposon libraries can be used to
      distinguish redundant pathways, decompose complex pathways into substituent
      modules, discriminate between enzyme homologs, and rapidly identify previously
      hypothetical enzymes in an unbiased genome-scale search. We use this technique to
      identify two genes, which we name desC and desD, are involved in the degradation
      of the lignin-derived aromatic compound sinapic acid in the non-model bacterium
      Novosphingobium aromaticivorans We show that DesC is a methyl-esterase acting on
      an intermediate formed during sinapic acid catabolism, providing the last enzyme
      in a proposed catabolic pathway. This approach will be particularly useful in the
      identification of complete pathways suitable for heterologous expression in
      metabolic engineering.Importance Identification of the genes involved in specific
      biochemical transformations is a key step in predicting microbial function from
      nucleic acid sequences and in engineering microbes to endow them with new
      functions. We have shown that new techniques for transposon mutagenesis can
      dramatically simplify this process and allow the rapid identification of genes in
      uncharacterized pathways. These techniques provide the necessary scale to fully
      elucidate complex biological networks such as those used to degrade mixtures of
      lignin-derived aromatic compounds.

PMID- 30217842
TI  - Engineering pseudochelin production in Myxococcus xanthus.
AB  - Myxobacteria utilize the catechol natural products myxochelin A and B in order to
      maintain their iron homeostasis. Recently, the production of these siderophores
      was reported from the marine bacterium Pseudoalteromonas piscicida S2040, along
      with a new myxochelin derivative named pseudochelin A. The latter features a
      characteristic imidazoline moiety, which was proposed to originate from an
      intramolecular condensation reaction of the beta-aminoethyl amide group in
      myxochelin B. To identify the enzyme catalyzing this conversion, we compared the
      myxochelin regulons of two myxobacterial strains, which solely produce myxochelin
      A and B, with P. piscicida S2040. This approach revealed a gene exclusive to the
      myxochelin regulon in P. piscicida S2040, coding for an enzyme of the
      amidohydrolase superfamily. To prove that this enzyme is indeed responsible for
      the postulated conversion, the reaction was reconstituted in vitro using a
      hexahistidyl-tagged recombinant protein made in Escherichia coli and myxochelin B
      as substrate. To test the production of pseudochelin A under in vivo conditions,
      the amidohydrolase gene was cloned into the myxobacterial plasmid pZJY156 and
      placed under the control of a copper-inducible promoter. The resulting vector was
      introduced into the myxobacterium Myxococcus xanthus DSM16526, a native producer
      of myxochelin A and B. Following the induction with copper, the myxobacterial
      expression strain was found to synthesize small quantities of pseudochelin A.
      Replacement of the copper-inducible promoter with the constitutive pilA promoter
      led to increased production levels in M. xanthus, which facilitated the isolation
      and subsequent structural verification of the heterologously produced
      compound.Importance In this study, an enzyme for imidazoline formation in
      pseudochelin biosynthesis was identified. Evidence for the involvement of this
      enzyme in the postulated reaction was obtained after in vitro reconstitution.
      Furthermore, the function of this enzyme was also demonstrated in vivo by
      transferring the corresponding gene into the bacterium Myxococcus xanthus, which
      thereby became a producer of pseudochelin A. Aside from clarifying the molecular
      basis of imidazoline formation in siderophore biosynthesis, we describe the
      heterologous expression of a gene in a myxobacterium without its chromosomal
      integration. Due to its metabolic proficiency, M. xanthus represents an
      interesting alternative to established host systems for the reconstitution and
      manipulation of biosynthetic pathways. Since the plasmid used in this study is
      easily adaptable for the expression of other enzymes as well, we expand the
      conventional expression strategy for myxobacteria, which is based on the
      integration of biosynthetic genes into the host genome.

PMID- 30217843
TI  - Coordinated Biosynthesis of the Purine Nucleoside Antibiotics Aristeromycin and
      Coformycin in Actinomycetes.
AB  - Purine nucleoside antibiotic pairs, concomitantly produced by a single strain,
      are an important group of microbial natural products. Here, we report a target
      directed genome mining approach to elucidate the biosynthesis of the purine
      nucleoside antibiotic pair aristeromycin (ARM) and coformycin (COF) in
      Micromonospora haikouensis DSM 45626 (a new producer for ARM and COF) and
      Streptomyces citricolor NBRC 13005 (a new COF producer). We also provide
      biochemical data that MacI and MacT function as unusual phosphorylases,
      catalyzing an irreversible reaction for the tailoring assembly of neplanocin A
      (NEP-A) and ARM. Moreover, we demonstrate that MacQ is shown to be an adenosine
      specific deaminase, likely relieving the potential "excess adenosine" for
      producing cells. Finally, we report that MacR, an annotated IMP dehydrogenase, is
      actually an NADPH-dependent GMP reductase, which potentially plays a salvage role
      for the efficient supply of the precursor pool. Hence, these findings illustrate
      a fine-tuned pathway for the biosynthesis of ARM and also open the way for the
      rational search for purine antibiotic pairs.IMPORTANCE ARM and COF are well known
      for their prominent biological activities and unusual chemical structures;
      however, the logic of their biosynthesis has long been poorly understood.
      Actually, the new insights into the ARM and COF pathway will not only enrich the
      biochemical repertoire for interesting enzymatic reactions but may also lay a
      solid foundation for the combinatorial biosynthesis of this group of antibiotics
      via a target-directed genome mining strategy.

PMID- 30217844
TI  - Phage-Antibiotic Synergy via Delayed Lysis.
AB  - When phages infect bacteria cultured in the presence of sublethal doses of
      antibiotics, the sizes of the phage plaques are significantly increased. This
      phenomenon is known as phage-antibiotic synergy (PAS). In this study, the
      observation of PAS was extended to a wide variety of bacterium-phage pairs using
      different classes of antibiotics. PAS was shown in both Gram-positive and Gram
      negative bacteria. Cells stressed with beta-lactam antibiotics filamented or
      swelled extensively, resulting in an increase in phage production. PAS was also
      sometimes observed in the presence of other classes of antibiotics with or
      without bacterial filamentation. The addition of antibiotics induced recA
      expression in various bacteria, but a recA deletion mutant strain of Escherichia
      coli also showed filamentation and PAS in the presence of quinolone antibiotics.
      The phage adsorption efficiency did not change in the presence of the antibiotics
      when the cell surfaces were enlarged as they filamented. Increases in the
      production of phage DNA and mRNAs encoding phage proteins were observed in these
      cells, with only a limited increase in protein production. The data suggest that
      PAS is the product of a prolonged period of particle assembly due to delayed
      lysis. The increase in the cell surface area far exceeded the increase in phage
      holin production in the filamented host cells, leading to a relatively limited
      availability of intracellular holins for aggregating and forming holes in the
      host membrane. Reactive oxygen species (ROS) stress also led to an increased
      production of phages, while heat stress resulted in only a limited increase in
      phage production.IMPORTANCE Phage-antibiotic synergy (PAS) has been reported for
      a decade, but the underlying mechanism has never been vigorously investigated.
      This study shows the presence of PAS from a variety of phage-bacterium-antibiotic
      pairings. We show that increased phage production resulted directly from a lysis
      delay caused by the relative shortage of holin in filamented bacterial hosts in
      the presence of sublethal concentrations of stress-inducing substances, such as
      antibiotics and reactive oxygen species (ROS).

PMID- 30217845
TI  - The Complete Pathway for Thiosulfate Utilization in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae is known to grow with thiosulfate as a sulfur source,
      and it produces more ethanol when using thiosulfate than using sulfate. Here, we
      report how it assimilates thiosulfate. S. cerevisiae absorbed thiosulfate into
      the cell through two sulfate permeases, Sul1 and Sul2. Two rhodaneses, Rdl1 and
      Rdl2, converted thiosulfate to a persulfide and sulfite. The persulfide was
      reduced by cellular thiols to H2S, and sulfite was reduced by sulfite reductase
      to H2S. Cysteine synthase incorporated H2S into O-acetyl-l-homoserine to produce
      l-homocysteine, which is the precursor for cysteine and methionine in S.
      cerevisiae Several other rhodaneses replaced Rdl1 and Rdl2 for thiosulfate
      utilization in the yeast. Thus, any organisms with the sulfate assimilation
      system potentially could use thiosulfate as a sulfur source, since rhodaneses are
      common in most organisms.IMPORTANCE The complete pathway of thiosulfate
      assimilation in baker's yeast is determined. The finding reveals the extensive
      overlap between sulfate and thiosulfate assimilation. Rhodanese is the only
      additional enzyme for thiosulfate utilization. The common presence of rhodanese
      in most organisms, including Bacteria, Archaea, and Eukarya, suggests that most
      organisms with the sulfate assimilation system also use thiosulfate. Since it
      takes less energy to reduce thiosulfate than sulfate for assimilation,
      thiosulfate has the potential to become a choice of sulfur in optimized media for
      industrial fermentation.

PMID- 30217846
TI  - Poisoning with Soman, an Organophosphorus Nerve Agent, Alters Fecal Bacterial
      Biota and Urine Metabolites: a case for Novel Signatures for Asymptomatic Nerve
      Agent Exposure.
AB  - The experimental pathophysiology of organophosphorus (OP) chemical exposure has
      been extensively reported. Here, we describe an altered fecal bacterial biota and
      urine metabolome that follows intoxication with soman, a lipophilic G class
      chemical warfare nerve agent. Non-anaesthetized Sprague-Dawley male rats were
      subcutaneously administered soman at 0.8 (sub-seizurogenic) or 1.0 (seizurogenic)
      of the median lethal dose (LD50) and evaluated for signs of toxicity. Animals
      were stratified based on seizing activity to evaluate effects of soman exposure
      on fecal bacterial biota and urine metabolites. Soman exposure reshaped fecal
      bacterial biota by altering Facklamia, Rhizobium, Bilophila, Enterobacter, and
      Morganella genera of the Firmicutes and Proteobacteria phyla, some of which are
      known to hydrolyze OPs. However, analogous changes were not observed in the
      bacterial biota of the ileum, which remained the same irrespective of dose or
      seizing status of animals after soman intoxication. However, at 75 days post
      soman exposure, bacterial biota stabilized and no differences were observed
      between groups. Interestingly, when considering just the seizing status of
      animals, we found that the urine metabolome was markedly different. Leukotriene
      C4, kynurenic acid, 5-hydroxyindoleacetic acid, norepinephrine, and aldosterone
      were excreted at much higher rates at 72 hrs in seizing animals, consistent with
      early multi-organ involvement during soman poisoning. These findings demonstrate
      the feasibility of using the dysbiosis of fecal bacterial biota in combination
      with urine metabolome alterations as forensic evidence for pre-symptomatic OP
      exposure temporally to enable administration of neuroprotective therapies of the
      future.Importance: The paucity of assays to determine physiologically relevant OP
      exposure presents an opportunity to explore the use of fecal bacteria as
      sentinels in combination with urine to assess changes in the exposed host. Recent
      advances in sequencing technologies and computational approaches have enabled
      researchers to survey large community level changes of gut bacterial biota and
      metabolomic changes in various biospecimens. Here, we profiled changes in fecal
      bacterial biota and urine metabolome following a chemical warfare nerve agent
      exposure. The significance of this work is a proof-of-concept that fecal
      bacterial biota and urine metabolites are two separate biospecimens rich in
      surrogate indicators suitable for monitoring OP exposure. The larger value of
      such an approach is that assays developed around these observations can be
      deployed at any setting with a moderate clinical chemistry and microbiology
      capability. This can enable estimation of the affected radius or to screen,
      triage, or rule out suspected cases of exposures in mass casualty scenarios,
      transportation accidents involving hazmats, refugee movements, humanitarian
      missions, and training settings when coupled to an established and validated
      decision-tree with clinical features.

PMID- 30217847
TI  - A New Group of Modular Xylanases in Glycoside Hydrolase Family 8 from Marine
      Bacteria.
AB  - Xylanases play a crucial role in the degradation of xylan in both terrestrial and
      marine environments. The endoxylanase XynB from the marine bacterium Glaciecola
      mesophila KMM 241 is a modular enzyme comprising a long N-terminal domain (NTD)
      (E44 to T562) with xylan-binding ability and a catalytic domain (CD) (T563 to
      E912) of glycoside hydrolase family 8 (GH8). In this study, the long NTD is
      confirmed to contain three different functional regions, which are NTD1 (E44 to
      D136), NTD2 (Y137 to A193), and NTD3 (L194 to T562). NTD1, mainly composed of
      eight beta-strands, functions as a new type of carbohydrate-binding module (CBM),
      which has xylan-binding ability but no sequence similarity to any known CBM.
      NTD2, mainly forming two alpha-helices, contains one of the alpha-helices of the
      catalytic domain's (alpha/alpha)6 barrel and therefore is essential for the
      activity of XynB, although it is far away from the catalytic domain in sequence.
      NTD3, next to the catalytic domain in sequence, is shown to be helpful in
      maintaining the thermostability of XynB. Thus, XynB represents a kind of xylanase
      with a new domain architecture. There are four other predicted glycoside
      hydrolase sequences with the same domain architecture and high sequence identity
      (>=80%) with XynB, all of which are from marine bacteria. Phylogenetic analysis
      shows that XynB and these homologs form a new group in GH8, representing a new
      class of marine bacterial xylanases. Our results shed light on xylanases,
      especially marine xylanases.IMPORTANCE Xylanases play a crucial role in natural
      xylan degradation and have been extensively used in industries such as food
      processing, animal feed, and kraft pulp biobleaching. Some marine bacteria have
      been found to secrete xylanases. Characterization of novel xylanases from marine
      bacteria has significance for both the clarification of xylan degradation
      mechanisms in the sea and the development of new enzymes for industrial
      application. With G. mesophila XynB as a representative, this study reveals a new
      group of the GH8 xylanases from marine bacteria, which have a distinct domain
      architecture and contain a novel carbohydrate-binding module. Thus, this study
      offers new knowledge on marine xylanases.

PMID- 30217848
TI  - Bioaerosol Sampler Choice Should Consider Efficiency and Ability of Samplers to
      Cover Microbial Diversity.
AB  - Bioaerosol studies tend to describe the microbial content and understand the
      aerosolization processes linked to diseases. Air samplers are used to collect,
      identify and quantify bioaerosols. Studies comparing the performance of air
      samplers have typically used a culture approach or have targeted a specific
      microorganism in laboratory settings. The objective of this study was to use
      environmental field samples to compare the efficiency of 3 high airflow rate
      samplers for describing bioaerosol diversity using a next-generation sequencing
      approach. Two liquid cyclonic impactors and one electrostatic filter dry sampler
      were used in four wastewater treatment plants to target bacterial diversity and
      in five dairy farms to target fungal diversity. The dry electrostatic sampler was
      consistently more powerful in collecting more fungal and bacterial OTUs.
      Substantial differences in OTU abundance between liquid and dry sampling were
      revealed. The majority of the diversity revealed by dry electrostatic sampling
      was not identified using the cyclonic liquid impactors. The findings on this work
      suggest that the choice of a bioaerosol sampler should include information about
      the efficiency and ability of samplers to cover microbial diversity. Although
      these results suggest that electrostatic filters result in better coverage of the
      microbial diversity amongst the tested air samplers, further studies are needed
      to confirm this hypothesis. While it is difficult to determine a single
      universally optimal air sampler, this work provides an in-depth look at some of
      the considerations that are essential when choosing an air sampler for studying
      the microbial ecology of bioaerosols.Importance Associating bioaerosol exposure
      and health problems is challenging and adequate exposure monitoring is a priority
      for scientist in the field. Conclusions that can be drawn from bioaerosol
      exposure studies are highly dependent on the design of the study and the
      methodologies used. The air sampling strategy is the first methodological step
      leading to an accurate interpretation of what is present in the air. Applying new
      molecular approaches to evaluate the efficiency of the different types of
      samplers used in the field is a necessary work around the traditional approaches
      and the biases they introduce to such studies. The results and conclusions
      provided in this manuscript should be taken in considerations when conducting a
      bioaerosol study.

PMID- 30217849
TI  - Catalase Expression in Azospirillum brasilense Sp7 Is Regulated by a Network
      Consisting of OxyR and Two RpoH Paralogs and Including an RpoE1->RpoH5 Regulatory
      Cascade.
AB  - The genome of Azospirillum brasilense encodes five RpoH sigma factors: two OxyR
      transcription regulators and three catalases. The aim of this study was to
      understand the role they play during oxidative stress and their regulatory
      interconnection. Out of the 5 paralogs of RpoH present in A. brasilense,
      inactivation of only rpoH1 renders A. brasilense heat sensitive. While transcript
      levels of rpoH1 were elevated by heat stress, those of rpoH3 and rpoH5 were
      upregulated by H2O2 Catalase activity was upregulated in A. brasilense and its
      rpoH::km mutants in response to H2O2 except in the case of the rpoH5::km mutant,
      suggesting a role for RpoH5 in regulating inducible catalase. Transcriptional
      analysis of the katN, katAI, and katAII genes revealed that the expression of
      katN and katAII was severely compromised in the rpoH3::km and rpoH5::km mutants,
      respectively. Regulation of katN and katAII by RpoH3 and RpoH5, respectively, was
      further confirmed in an Escherichia coli two-plasmid system. Regulation of katAII
      by OxyR2 was evident by a drastic reduction in growth, KatAII activity, and
      katAII::lacZ expression in an oxyR2::km mutant. This study reports the
      involvement of RpoH3 and RpoH5 sigma factors in regulating oxidative stress
      response in alphaproteobacteria. We also report the regulation of an inducible
      catalase by a cascade of alternative sigma factors and an OxyR. Out of the three
      catalases in A. brasilense, those corresponding to katN and katAII are regulated
      by RpoH3 and RpoH5, respectively. The expression of katAII is regulated by a
      cascade of RpoE1->RpoH5 and OxyR2.IMPORTANCE In silico analysis of the A.
      brasilense genome showed the presence of multiple paralogs of genes involved in
      oxidative stress response, which included 2 OxyR transcription regulators and 3
      catalases. So far, Deinococcus radiodurans and Vibrio cholerae are known to
      harbor two paralogs of OxyR, and Sinorhizobium meliloti harbors three catalases.
      We do not yet know how the expression of multiple catalases is regulated in any
      bacterium. Here we show the role of multiple RpoH sigma factors and OxyR in
      regulating the expression of multiple catalases in A. brasilense Sp7. Our work
      gives a glimpse of systems biology of A. brasilense used for responding to
      oxidative stress.

PMID- 30217850
TI  - Chronic Airway Colonization by Achromobacter xylosoxidans in Cystic Fibrosis
      Patients Is Not Sustained by Their Domestic Environment.
AB  - Achromobacter spp. are nonfermentative Gram-negative bacilli considered emergent
      pathogens in cystic fibrosis (CF). Although some cross-transmission events
      between CF patients have been described, Achromobacter strains were mostly
      patient specific, suggesting sporadic acquisitions from nonhuman reservoirs.
      However, sources of these emergent CF pathogens remain unknown. A large
      collection of specimens (n = 273) was sampled in the homes of 3 CF patients
      chronically colonized by Achromobacter xylosoxidans with the aim of evaluating
      the potential role of domestic reservoirs in sustaining airway colonization of
      the patients. Samples were screened for the presence of Achromobacter by using
      genus-specific molecular detection. Species identification, multilocus genotypes,
      and antimicrobial susceptibility patterns observed for environmental isolates
      were compared with those of clinical strains. Patient homes hosted a high
      diversity of Achromobacter species (n = 7), including Achromobacter mucicolens
      and A. animicus, two species previously isolated from human samples only, and
      genotypes (n = 15), all showing an overall susceptibility to antimicrobial
      agents. Achromobacter strains were mostly isolated from indoor moist environments
      and siphons, which are potential reservoirs for several CF emerging pathogens. A.
      xylosoxidans, the worldwide prevalent species colonizing CF patients, was not the
      major Achromobacter species inhabiting domestic environments. A. xylosoxidans
      genotypes chronically colonizing the patients were not detected in their
      household environments. These results support the notions that the domestic
      environment could not be incriminated in sustained patient colonization and that
      after initial colonization, the environmental survival of A. xylosoxidans clones
      adapted to the CF airways is probably impaired.IMPORTANCE Achromobacter spp. are
      worldwide emerging opportunistic pathogens in CF patients, able to chronically
      colonize the respiratory tract. Apart from regular consultations at the hospital
      CF center, patients spend most of their time at home. Colonization from nonhuman
      sources has been suggested, but the presence of Achromobacter spp. in CF
      patients' homes has not been explored. The domestic environments of CF patients
      chronically colonized by Achromobacter, especially wet environments, host several
      opportunistic pathogens, including a large diversity of Achromobacter species and
      genotypes. However, Achromobacter genotypes colonizing the patients were not
      detected in their domestic environments, making it unlikely that a shuttle
      between environment and CF airways is involved in persisting colonization. This
      also suggests that once the bacteria have adapted to the respiratory tract, their
      survival in the domestic environment is presumably impaired. Nevertheless,
      measures for reducing domestic patient exposure should be targeted on evacuation
      drains, which are frequently contaminated by CF opportunistic pathogens.

PMID- 30217851
TI  - Diversity of Active Viral Infections within the Sphagnum Microbiome.
AB  - Sphagnum-dominated peatlands play an important role in global carbon storage and
      represent significant sources of economic and ecological value. While recent
      efforts to describe microbial diversity and metabolic potential of the Sphagnum
      microbiome have demonstrated the importance of its microbial community, little is
      known about the viral constituents. We used metatranscriptomics to describe the
      diversity and activity of viruses infecting microbes within the Sphagnum peat
      bog. The vegetative portions of six Sphagnum plants were obtained from a peatland
      in northern Minnesota, and the total RNA was extracted and sequenced.
      Metatranscriptomes were assembled and contigs were screened for the presence of
      conserved virus marker genes. Using bacteriophage capsid protein gp23 as a marker
      for phage diversity, we identified 33 contigs representing undocumented phages
      that were active in the community at the time of sampling. Similarly, RNA
      dependent RNA polymerase and the nucleocytoplasmic large DNA virus (NCLDV) major
      capsid protein were used as markers for single-stranded RNA (ssRNA) viruses and
      NCLDV, respectively. In total, 114 contigs were identified as originating from
      undescribed ssRNA viruses, 22 of which represent nearly complete genomes. An
      additional 64 contigs were identified as being from NCLDVs. Finally, 7 contigs
      were identified as putative virophage or polinton-like viruses. We developed co
      occurrence networks with these markers in relation to the expression of potential
      host housekeeping gene rpb1 to predict virus-host relationships, identifying 13
      groups. Together, our approach offers new tools for the identification of virus
      diversity and interactions in understudied clades and suggests that viruses may
      play a considerable role in the ecology of the Sphagnum microbiome.IMPORTANCE
      Sphagnum-dominated peatlands play an important role in maintaining atmospheric
      carbon dioxide levels by modifying conditions in the surrounding soil to favor
      the growth of Sphagnum over that of other plant species. This lowers the rate of
      decomposition and facilitates the accumulation of fixed carbon in the form of
      partially decomposed biomass. The unique environment produced by Sphagnum
      enriches for the growth of a diverse microbial consortia that benefit from and
      support the moss's growth, while also maintaining the hostile soil conditions.
      While a growing body of research has begun to characterize the microbial groups
      that colonize Sphagnum, little is currently known about the ecological factors
      that constrain community structure and define ecosystem function. Top-down
      population control by viruses is almost completely undescribed. This study
      provides insight into the significant viral influence on the Sphagnum microbiome
      and identifies new potential model systems to study virus-host interactions in
      the peatland ecosystem.

PMID- 30217852
TI  - Filling the void: Introducing aromatic interactions into solvent tunnels towards
      lipase stability in methanol.
AB  - Enhanced stability in organic solvents is a desirable feature for enzymes
      implemented under industrial conditions. Lipases potential as biocatalysts is
      mainly limited by denaturation in polar alcohols. In this study we focused on
      selected solvent tunnels in lipase from Geobacillus stearothermophilus T6 to
      improve its stability in methanol during biodiesel synthesis. Using rational
      mutagenesis, bulky aromatic residues were incorporated in order to occupy solvent
      channels and induce aromatic interactions leading to a better inner core packing.
      Each solvent tunnel was systematically analyzed with respect to its chemical and
      structural characteristics. Selected residues were replaced with Phe, Tyr or Trp.
      Overall, 16 mutants were generated and screened in 60% methanol, from which 3
      variants showed elevated stability up to 81-fold compared with wild-type. All
      stabilizing mutations were found in the longest tunnel detected in the "closed
      lid" x-ray structure. Combining the Phe substitutions created double mutant
      A187F/L360F with an increase in Tm of +7 degrees C in methanol and a 3-fold
      increase in biodiesel synthesis yield from waste chicken oil. Kinetic analysis
      with p-nitrophenyl laurate revealed that all mutants displayed lower hydrolysis
      rates (kcat ), though mostly their stability properties determined the
      transesterification capability. Seven crystal structures of different variants
      were solved disclosing new pi-pi or CH/pi intramolecular interactions emphasizing
      the significance of aromatic interactions to improved solvent stability. This
      rational approach could be implemented in other enzymes for stabilization in
      organic solvents.IMPORTANCE Enzymatic synthesis in organic solvents holds
      increasing industrial opportunities in many fields, however, one major obstacle
      is the limited stability of biocatalysts in such a denaturing environment.
      Aromatic interactions play a major role in protein folding and stability and we
      were inspired by this to re-design enzyme voids. Rational protein engineering of
      solvent tunnels of lipase from Geobacillus stearothermophilus is presented here,
      offering a promising approach to introduce new aromatic interactions within the
      enzyme core. We discovered that longer tunnels leading from the surface to the
      enzyme active site were more beneficial targets for mutagenesis for improving
      lipase stability in methanol during biodiesel biosynthesis. Structural analysis
      of the variants confirmed the generation of new interactions involving aromatic
      residues. This work provides insights into stability-driven enzyme design by
      targeting solvent channels void.

PMID- 30217853
TI  - In Planta Sporulation of Frankia spp. as a Determinant of Alder-Symbiont
      Interactions.
AB  - The Alnus genus forms symbiosis with the actinobacteria Frankia spp. and
      ectomycorrhizal fungi. Two types of Frankia lineages can be distinguished based
      on their ability to sporulate in planta Spore-positive (Sp+) strains are
      predominant on Alnus incana and Alnus viridis in highlands, while spore-negative
      (Sp-) strains are mainly associated with Alnus glutinosa in lowlands. Here, we
      investigated whether the Sp+ predominance in nodules is due to host selection of
      certain Frankia genotypes from soil communities or the result of the ecological
      history of the alder stand soil, as well as the effect of the sporulation
      genotype on the ectomycorrhizal (ECM) communities. Trapping experiments were
      conducted using A. glutinosa, A. incana, and A. viridis plantlets on 6 soils,
      differing in the alder species and the frequency of Sp+ nodules in the field.
      Higher diversity of Frankia spp. and variation in Sp+ frequencies were observed
      in the trapping than in the fields. Both indigenous and trapping species shape
      Frankia community structure in trapped nodules. Nodulation impediments were
      observed under several trapping conditions in Sp+ soils, supporting a narrower
      host range of Sp+ Frankia species. A. incana and A. viridis were able to
      associate equally with compatible Sp+ and Sp- strains in the greenhouse.
      Additionally, no host shift was observed for Alnus-specific ECM, and the
      sporulation genotype of Frankia spp. defined the ECM communities on the host
      roots. The symbiotic association is likely determined by the host range, the soil
      history, and the type of in planta Frankia species. These results provide an
      insight into the biogeographical drivers of alder symbionts in the Holarctic
      region.IMPORTANCE Most Frankia-actinorhiza plant symbioses are capable of high
      rates of nitrogen fixation comparable to those found on legumes. Yet, our
      understanding of the ecology and distribution of Frankia spp. is still very
      limited. Several studies have focused on the distribution patterns of Frankia
      spp., demonstrating a combination of host and pedoclimatic parameters in their
      biogeography. However, very few have considered the in planta sporulation form of
      the strain, although it is a unique feature among all symbiotic plant-associated
      microbes. Compared with Sp- Frankia strains, Sp+ strains would be obligate
      symbionts that are highly dependent on the presence of a compatible host species
      and with lower efficiency in nitrogen fixation. Understanding the biogeographical
      drivers of Sp+ Frankia strains might help elucidate the ecological role of in
      planta sporulation and the extent to which this trait mediates host-partner
      interactions in the alder-Frankia-ECM fungal symbiosis.

PMID- 30217855
TI  - Kidney cancer: The next decade.
AB  - Chris Boshoff, Senior Vice President of Immuno-Oncology, Translational and Early
      Development at Pfizer, and colleagues Samra Turajlic and Charles Swanton from the
      Francis Crick Institute and University College London give us their personal
      point of view on new insights and future therapeutic approaches for renal cancer.

PMID- 30217854
TI  - CRISPR-Cas9 and CRISPR-Assisted Cytidine Deaminase Enable Precise and Efficient
      Genome Editing in Klebsiella pneumoniae.
AB  - Klebsiella pneumoniae is a promising industrial microorganism as well as a major
      human pathogen. The recent emergence of carbapenem-resistant K. pneumoniae has
      posed a serious threat to public health worldwide, emphasizing a dire need for
      novel therapeutic means against drug-resistant K. pneumoniae Despite the critical
      importance of genetics in bioengineering, physiology studies, and therapeutic
      means development, genome editing, in particular, the highly desirable scarless
      genetic manipulation in K. pneumoniae, is often time-consuming and laborious.
      Here, we report a two-plasmid system, pCasKP-pSGKP, used for precise and
      iterative genome editing in K. pneumoniae By harnessing the clustered regularly
      interspaced short palindromic repeat (CRISPR)-Cas9 genome cleavage system and the
      lambda Red recombination system, pCasKP-pSGKP enabled highly efficient genome
      editing in K. pneumoniae using a short repair template. Moreover, we developed a
      cytidine base-editing system, pBECKP, for precise C->T conversion in both the
      chromosomal and plasmid-borne genes by engineering the fusion of the cytidine
      deaminase APOBEC1 and a Cas9 nickase. By using both the pCasKP-pSGKP and the
      pBECKP tools, the bla KPC-2 gene was confirmed to be the major factor that
      contributed to the carbapenem resistance of a hypermucoviscous carbapenem
      resistant K. pneumoniae strain. The development of the two editing tools will
      significantly facilitate the genetic engineering of K. pneumoniae IMPORTANCE
      Genetics is a key means to study bacterial physiology. However, the highly
      desirable scarless genetic manipulation is often time-consuming and laborious for
      the major human pathogen K. pneumoniae We developed a CRISPR-Cas9-mediated genome
      editing method and a cytidine base-editing system, enabling rapid, highly
      efficient, and iterative genome editing in both industrial and clinically
      isolated K. pneumoniae strains. We applied both tools in dissecting the drug
      resistance mechanism of a hypermucoviscous carbapenem-resistant K. pneumoniae
      strain, elucidating that the bla KPC-2 gene was the major factor that contributed
      to the carbapenem resistance of the hypermucoviscous carbapenem-resistant K.
      pneumoniae strain. Utilization of the two tools will dramatically accelerate a
      wide variety of investigations in diverse K. pneumoniae strains and relevant
      Enterobacteriaceae species, such as gene characterization, drug discovery, and
      metabolic engineering.

PMID- 30217857
TI  - Fetal hydrops: diagnosis and prognosis.

PMID- 30217858
TI  - Neonatal outcomes following new reimbursement limitations on palivizumab in
      Italy.
AB  - OBJECTIVE: To evaluate the impact of new reimbursement decisions for palivizumab
      treatment on respiratory syncytial virus (RSV) hospitalisations and the
      concomitant number of palivizumab prescriptions for infants aged <2 years.
      DESIGN: We compared the RSV hospitalisation rates in infants before and after
      implementation of new limitations during three RSV seasons 2014-2017. SETTING:
      Population aged <2 years at the beginning of each RSV seasons extracted from
      regional health systems (Lazio region, 2016, 5 898 124 inhabitants and 47 595
      births). PATIENTS: Out of 70 323 infants, 5895 (8.4%) premature babies
      (gestational age (GA) <37 weeks) were followed before-after Italian Medicines
      Agency (AIFA)-2016 limitations. INTERVENTION: In 2016, AIFA, following the
      American Academy of Pediatrics guidelines, decided to limit coverage of
      palivizumab prophylaxis (GA <=29 weeks). MAIN OUTCOMES MEASURES: Trend of
      hospitalisations by months and rate of RSV before-after new restrictions were
      analysed. Palivizumab prescriptions and costs for National Health Service (NHS)
      were considered. RESULTS: In a population of 284 902 aged <2 years, the number of
      hospitalisations due to RSV infection was 1729. Following AIFA-2016 limitations,
      a reduction in the number of RSV infection-based hospitalisations from 6.3/1000
      (95% CI 6.0 to 6.7) to 5.5/1000 (95% CI 5.0 to 5.9) was observed. Palivizumab
      showed a concomitant reduction of 48% in the number of prescriptions (saving ?750
      000 for the NHS). No differences of GA, age on admission or severity of RSV
      infection were observed. CONCLUSIONS: Implementation of the new palivizumab
      reimbursement criteria was not associated with an increase in the RSV
      hospitalisation rate for children aged <2 years despite a significant reduction
      in the number of palivizumab prescriptions.

PMID- 30217859
TI  - Shorter treatment for latent TB.

PMID- 30217860
TI  - 'Death is not the answer': the challenge of measuring the impact of early warning
      systems.

PMID- 30217861
TI  - Mass antibiotic distribution to reduce mortality among preschool children?

PMID- 30217862
TI  - What works in preventing obesity?

PMID- 30217863
TI  - The exquisitely cooperative nature of Orai1 channel activation.

PMID- 30217864
TI  - The binding of Class II sRNA MgrR to two different sites on matchmaker protein
      Hfq enables efficient competition for Hfq and annealing to regulated mRNAs.
AB  - MgrR is an Hfq-dependent sRNA, whose transcription is controlled by the level of
      Mg2+ ions in Escherichia coli MgrR belongs to Class II sRNAs because its
      stability in the cell is affected by mutations in Hfq differently than canonical,
      Class I sRNAs. Here, we examined the effect of mutations in RNA binding sites of
      Hfq on the kinetics of the annealing of MgrR to two different target mRNAs, eptB
      and ygdQ, by global data fitting of the reaction kinetics monitored by gel
      electrophoresis of intermediates and products. The data showed that the mutation
      on the rim of the Hfq ring trapped MgrR on Hfq preventing the annealing of MgrR
      to either mRNA. The mutation in the distal face slowed the ternary complex
      formation and affected the release of MgrR-mRNA complexes from Hfq, while the
      mutation in the proximal face weakened the MgrR binding to Hfq and in this way
      affected the annealing. Moreover, competition assays established that MgrR bound
      to both faces of Hfq and competed against other sRNAs. Further studies showed
      that uridine-rich sequences located in less structurally stable regions served as
      Hfq binding sites in each mRNA. Overall, the data show that the binding of MgrR
      sRNA to both faces of the Hfq ring enables it to efficiently anneal to target
      mRNAs. It also confers on MgrR a competitive advantage over other sRNAs, which
      could contribute to efficient cellular response to changes in magnesium
      homeostasis.

PMID- 30217865
TI  - tRNA 3'-amino-tailing for stable amino acid attachment.
AB  - Amino acids are attached to the tRNA 3'-end as a prerequisite for entering the
      ribosome for protein synthesis. Amino acid attachment also gives tRNA access to
      nonribosomal cellular activities. However, the normal attachment is via an ester
      linkage between the carboxylic group of the amino acid and the 3'-hydroxyl of the
      terminal A76 ribose in tRNA. The instability of this ester linkage has severely
      hampered studies of aminoacyl-tRNAs. Although the use of 3'-amino-3'-deoxy A76 in
      a 3'-amino-tailed tRNA provides stable aminoacyl attachment via an amide linkage,
      there are multiple tailing protocols and the efficiency of each relative to the
      others is unknown. Here we compare five different tailing protocols in parallel,
      all dependent on the CCA-adding enzyme [CTP(ATP): tRNA nucleotidyl transferase;
      abbreviated as the CCA enzyme] to exchange the natural ribose with the modified
      one. We show that the most efficient protocol is achieved by the CCA-catalyzed
      pyrophosphorolysis removal of the natural A76 in equilibrium with the addition of
      the appropriate ATP analog to synthesize the modified 3'-end. This protocol for
      3'-amino-tailing affords quantitative and stable attachment of a broad range of
      amino acids to tRNA, indicating its general utility for studies of aminoacyl
      tRNAs in both canonical and noncanonical activities.

PMID- 30217867
TI  - Correction: Conserved, disordered C terminus of DnaK enhances cellular survival
      upon stress and DnaK in vitro chaperone activity.

PMID- 30217866
TI  - Dual-layer transposon repression in heads of Drosophila melanogaster.
AB  - piRNA-mediated repression of transposable elements (TE) in the germline limits
      the accumulation of mutations caused by their transposition. It is not clear
      whether the piRNA pathway plays a role in adult, nongonadal tissues in Drosophila
      melanogaster. To address this question, we analyzed the small RNA content of
      adult Drosophila melanogaster heads. We found that the varying amount of piRNA
      sized, ping-pong positive molecules in heads correlates with contamination by
      gonadal tissue during RNA extraction, suggesting that most of the piRNAs detected
      in heads originate from gonads. We next sequenced the heads of wild-type and piwi
      mutants to address whether piwi loss of function would affect the low amount of
      piRNA-sized, ping-pong negative molecules that are still detected in heads hand
      checked to avoid gonadal contamination. We find that loss of piwi does not
      significantly affect these 24-28 nt RNAs. Instead, we observe increased siRNA
      levels against the majority of Drosophila TE families. To determine the effect of
      this siRNA level change on transposon expression, we sequenced the transcriptome
      of wild-type, piwi, dicer-2 and piwi, dicer-2 double-mutant heads. We find that
      RNA expression levels of the majority of TE in piwi or dicer-2 mutants remain
      unchanged and that TE transcripts increase only in piwi, dicer-2 double-mutants.
      These results lead us to suggest a dual-layer model for TE repression in adult
      somatic tissues. Piwi-mediated gene silencing established during embryogenesis
      constitutes the first layer of TE repression whereas Dicer-2-dependent siRNA
      mediated silencing provides a backup mechanism to repress TEs that escape
      silencing by Piwi.

PMID- 30217868
TI  - An unlikely heme chaperone confirmed at last.
AB  - Labile heme, as opposed to heme that is tightly bound within proteins, is thought
      to require a chaperone to be trafficked within the cell due to its cytotoxicity,
      but the identity of this chaperone was not known. A new study reveals that an
      unlikely protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is a heme
      chaperone that binds and transfers labile heme to downstream target proteins.
      These results provide a new framework for understanding heme homeostasis and
      raise intriguing questions regarding the intersection of heme transport,
      carbohydrate metabolism, and intracellular signaling.

PMID- 30217869
TI  - 2019 Herbert Tabor Young Investigator Awards: Call for nominations.

PMID- 30217870
TI  - High-frequency oscillatory ventilation with volume guarantee: a single-centre
      experience.
AB  - OBJECTIVE: High-frequency oscillatory ventilation (HFOV) is widely used in
      neonatology. The Drager Babylog VN500 ventilator offers volume-guaranteed HFOV
      (HFOV-VG) mode when the high-frequency tidal volume (VThf) to be delivered can be
      set. We investigated how HFOV-VG maintains VThf in the short and longer term and
      how it affects other ventilator parameters and blood gases. METHODS: We
      downloaded ~3.2 million seconds (36.7 days) of ventilator data from 17 infants
      ventilated using HFOV-VG during clinical care with 1 Hz sampling rate. To process
      and analyse the data, we used the Python computer language. RESULTS: Overall, the
      median VThf was 1.93 mL/kg (IQR 1.64-2.45 mL/kg). The difference between set and
      delivered tidal volume was <0.2 mL/kg for 83% of time. In the individual
      recordings, the median VThf ranged between 1.44 and 3.31 mL/kg. During HFOV-VG,
      the VThf varied from 1 second to another, but it was very close to the target
      value when averaged over 5 min periods. After weight correction, the VThf or the
      diffusion coefficient of carbon dioxide (DCO2) showed weak inverse correlation
      with partial pressure of CO2(pCO2) (for VThf, r=-0.162, 95% CI -0.282 to -0.037,
      p=0.01). Uncorrected values showed no correlation. Of the 53 blood gas
      measurements taken when VThf was >2.5 mL/kg, there were only six (11%) with a
      pCO2 >8 kPa. CONCLUSIONS: During HFOV-VG, the tidal volume of oscillations varies
      in the short term but is maintained very close to the target over the longer
      term. VThf or DCO2 have poor correlation with CO2 levels but a volume of >2.5
      mL/kg VThf is rarely needed.

PMID- 30217872
TI  - An Interleukin-1 Signature in Breast Cancer Treated with Interleukin-1 Receptor
      Blockade: Implications for Treating Cytokine Release Syndrome of Checkpoint
      Inhibitors.
AB  - In this issue of Cancer Research, Wu and colleagues show that IL1b orchestrates
      tumor-promoting inflammation in breast cancer and can be targeted in patients
      using an IL1 receptor antagonist. Cancer Res; 78(18); 5200-2. (c)2018 AACRSee
      related article by Wu et al., p. 5243.

PMID- 30217873
TI  - Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor
      Acute Lymphoblastic Leukemia.
AB  - It has been proposed that children with acute lymphoblastic leukemia (ALL) are
      born with a dysregulated immune function that together with postnatal
      environmental exposures causes childhood ALL. Despite its importance for the
      understanding of ALL etiology, this hypothesis has been inadequately explored. In
      a population-based case-control study, we measured the concentrations of 10
      cytokines and other inflammatory markers on neonatal dried blood spots from 178
      children who at ages 1 to 9 years were diagnosed with B-cell precursor ALL and
      178 matched controls. Through linkage with Danish nationwide registers, we also
      assessed whether neonatal inflammatory markers were associated with previously
      demonstrated risk factors for childhood ALL. Children who developed B-cell
      precursor ALL had significantly lower neonatal concentrations of IL8, soluble IL6
      receptor (sIL6R) alpha, TGFbeta1, monocyte chemotactic protein (MCP)-1, and C
      reactive protein (CRP) and higher concentrations of IL6, IL17, and IL18 compared
      with matched controls. Concentrations of IL10 were below the detection level for
      both patients and controls. Birth order (IL18 and CRP), gestational age
      (sIL6Ralpha, TGFbeta1, and CRP), and sex (sIL6Ralpha, IL8, and CRP), but not
      maternal age, infections during pregnancy, birth weight nor mode of delivery were
      significantly associated with the neonatal concentrations of inflammatory
      markers. Our findings support the hypothesis that children who later develop B
      cell precursor ALL are born with a dysregulated immune function.Significance:
      Children who develop acute lymphoblastic leukemia are immunologically distinct at
      birth and could potentially react abnormally to infections in early childhood.
      Cancer Res; 78(18); 5458-63. (c)2018 AACR.

PMID- 30217874
TI  - Correction: Carbonyl Reductase 1 Offers a Novel Therapeutic Target to Enhance
      Leukemia Treatment by Arsenic Trioxide.

PMID- 30217875
TI  - Editor's Note: In vitro and In vivo Molecular Evidence for Better Therapeutic
      Efficacy of ABT-627 and Taxotere Combination in Prostate Cancer.

PMID- 30217876
TI  - Retraction: Gemcitabine Sensitivity Can Be Induced in Pancreatic Cancer Cells
      through Modulation of miR-200 and miR-21 Expression by Curcumin or Its Analogue
      CDF.

PMID- 30217877
TI  - Retraction: 3,3'-Diindolylmethane Enhances Chemosensitivity of Multiple
      Chemotherapeutic Agents in Pancreatic Cancer.

PMID- 30217878
TI  - Retraction: Antitumor Activity of Gemcitabine and Oxaliplatin Is Augmented by
      Thymoquinone in Pancreatic Cancer.

PMID- 30217879
TI  - Retraction: Down-regulation of Platelet-Derived Growth Factor-D Inhibits Cell
      Growth and Angiogenesis through Inactivation of Notch-1 and Nuclear Factor-kappaB
      Signaling.

PMID- 30217880
TI  - Retraction: Down-regulation of Forkhead Box M1 Transcription Factor Leads to the
      Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells.

PMID- 30217881
TI  - Retraction: Inhibition of Angiogenesis and Invasion by 3,3'-Diindolylmethane Is
      Mediated by the Nuclear Factor-kappaB Downstream Target Genes MMP-9 and uPA that
      Regulated Bioavailability of Vascular Endothelial Growth Factor in Prostate
      Cancer.

PMID- 30217882
TI  - Retraction: Potentiation of the Effect of Erlotinib by Genistein in Pancreatic
      Cancer: The Role of Akt and Nuclear Factor-kappaB.

PMID- 30217883
TI  - Retraction: Down-regulation of Androgen Receptor by 3,3'-Diindolylmethane
      Contributes to Inhibition of Cell Proliferation and Induction of Apoptosis in
      Both Hormone-Sensitive LNCaP and Insensitive C4-2B Prostate Cancer Cells.

PMID- 30217884
TI  - Retraction: Epidermal Growth Factor Receptor-Related Protein Inhibits Cell Growth
      and Invasion in Pancreatic Cancer.

PMID- 30217886
TI  - Retraction: Down-regulation of Notch-1 Inhibits Invasion by Inactivation of
      Nuclear Factor-kappaB, Vascular Endothelial Growth Factor, and Matrix
      Metalloproteinase-9 in Pancreatic Cancer Cells.

PMID- 30217885
TI  - Retraction: Antitumor and Antimetastatic Activities of Docetaxel Are Enhanced by
      Genistein through Regulation of Osteoprotegerin/Receptor Activator of Nuclear
      Factor-kappaB (RANK)/RANK Ligand/MMP-9 Signaling in Prostate Cancer.

PMID- 30217887
TI  - Retraction: Antitumor Activity of Epidermal Growth Factor Receptor-Related
      Protein Is Mediated by Inactivation of ErbB Receptors and Nuclear Factor-kappaB
      in Pancreatic Cancer.

PMID- 30217888
TI  - Intrinsic excitement in cerebellar nuclei neurons during learning.

PMID- 30217889
TI  - The remarkable legacy of a father's diet on the health of his offspring.

PMID- 30217890
TI  - Pressure-induced phase transitions and superconductivity in a black phosphorus
      single crystal.
AB  - We report a thorough study of the transport properties of the normal and
      superconducting states of black phosphorus (BP) under magnetic field and high
      pressure with a large-volume apparatus that provides hydrostatic pressure to
      induce transitions from the layered A17 phase to the layered A7 phase and to the
      cubic phase of BP. Quantum oscillations can be observed at P >= 1 GPa in both
      resistivity and Hall voltage, and their evolutions with pressure in the A17 phase
      imply a continuous enlargement of Fermi surface. A significantly large
      magnetoresistance (MR) at low temperatures is observed in the A7 phase that
      becomes superconducting below a superconducting transition temperature T c ~ 6-13
      K. T c increases continuously with pressure on crossing the A7 to the cubic phase
      boundary. The strong MR effect can be fit by a modified Kohler's rule. A
      correlation between T c and fitting parameters suggests that phonon-mediated
      interactions play dominant roles in driving the Cooper pairing, which is further
      supported by our density functional theory (DFT) calculations. The change of
      effective carrier mobility in the A17 phase under pressure derived from the MR
      effect is consistent with that obtained from the temperature dependence of the
      quantum oscillations. In situ single-crystal diffraction under high pressure
      indicates a total structural reconstruction instead of simple stretching of the
      A17 phase layers in the A17-to-A7-phase transition. This finding helps us to
      interpret transport properties on crossing the phase transition under high
      pressure.

PMID- 30217891
TI  - Physical basis for long-distance communication along meiotic chromosomes.
AB  - Viable gamete formation requires segregation of homologous chromosomes connected,
      in most species, by cross-overs. DNA double-strand break (DSB) formation and the
      resulting cross-overs are regulated at multiple levels to prevent overabundance
      along chromosomes. Meiotic cells coordinate these events between distant sites,
      but the physical basis of long-distance chromosomal communication has been
      unknown. We show that DSB hotspots up to ~200 kb (~35 cM) apart form clusters via
      hotspot-binding proteins Rec25 and Rec27 in fission yeast. Clustering coincides
      with hotspot competition and interference over similar distances. Without Tel1
      (an ATM tumor-suppressor homolog), DSB and crossover interference become
      negative, reflecting coordinated action along a chromosome. These results
      indicate that DSB hotspots within a limited chromosomal region and bound by their
      protein determinants form a clustered structure that, via Tel1, allows only one
      DSB per region. Such a "roulette" process within clusters explains the observed
      pattern of crossover interference in fission yeast. Key structural and regulatory
      components of clusters are phylogenetically conserved, suggesting conservation of
      this vital regulation. Based on these observations, we propose a model and
      discuss variations in which clustering and competition between DSB sites leads to
      DSB interference and in turn produces crossover interference.

PMID- 30217892
TI  - Functional diversification of the NleG effector family in enterohemorrhagic
      Escherichia coli.
AB  - The pathogenic strategy of Escherichia coli and many other gram-negative
      pathogens relies on the translocation of a specific set of proteins, called
      effectors, into the eukaryotic host cell during infection. These effectors act in
      concert to modulate host cell processes in favor of the invading pathogen.
      Injected by the type III secretion system (T3SS), the effector arsenal of
      enterohemorrhagic E. coli (EHEC) O157:H7 features at least eight individual NleG
      effectors, which are also found across diverse attaching and effacing pathogens.
      NleG effectors share a conserved C-terminal U-box E3 ubiquitin ligase domain that
      engages with host ubiquitination machinery. However, their specific functions and
      ubiquitination targets have remained uncharacterized. Here, we identify host
      proteins targeted for ubiquitination-mediated degradation by two EHEC NleG family
      members, NleG5-1 and NleG2-3. NleG5-1 localizes to the host cell nucleus and
      targets the MED15 subunit of the Mediator complex, while NleG2-3 resides in the
      host cytosol and triggers degradation of Hexokinase-2 and SNAP29. Our structural
      studies of NleG5-1 reveal a distinct N-terminal alpha/beta domain that is
      responsible for interacting with host protein targets. The core of this domain is
      conserved across the NleG family, suggesting this domain is present in
      functionally distinct NleG effectors, which evolved diversified surface residues
      to interact with specific host proteins. This is a demonstration of the
      functional diversification and the range of host proteins targeted by the most
      expanded effector family in the pathogenic arsenal of E. coli.

PMID- 30217893
TI  - High-resolution structures of HIV-1 Gag cleavage mutants determine structural
      switch for virus maturation.
AB  - HIV-1 maturation occurs via multiple proteolytic cleavages of the Gag
      polyprotein, causing rearrangement of the virus particle required for
      infectivity. Cleavage results in beta-hairpin formation at the N terminus of the
      CA (capsid) protein and loss of a six-helix bundle formed by the C terminus of CA
      and the neighboring SP1 peptide. How individual cleavages contribute to changes
      in protein structure and interactions, and how the mature, conical capsid forms,
      are poorly understood. Here, we employed cryoelectron tomography to determine
      morphology and high-resolution CA lattice structures for HIV-1 derivatives in
      which Gag cleavage sites are mutated. These analyses prompt us to revise current
      models for the crucial maturation switch. Unlike previously proposed, cleavage on
      either terminus of CA was sufficient, in principle, for lattice maturation, while
      complete processing was needed for conical capsid formation. We conclude that
      destabilization of the six-helix bundle, rather than beta-hairpin formation,
      represents the main determinant of structural maturation.

PMID- 30217894
TI  - Relation between single-molecule properties and phase behavior of intrinsically
      disordered proteins.
AB  - Proteins that undergo liquid-liquid phase separation (LLPS) have been shown to
      play a critical role in many physiological functions through formation of
      condensed liquid-like assemblies that function as membraneless organelles within
      biological systems. To understand how different proteins may contribute
      differently to these assemblies and their functions, it is important to
      understand the molecular driving forces of phase separation and characterize
      their phase boundaries and material properties. Experimental studies have shown
      that intrinsically disordered regions of these proteins are a major driving
      force, as many of them undergo LLPS in isolation. Previous work on polymer
      solution phase behavior suggests a potential correspondence between
      intramolecular and intermolecular interactions that can be leveraged to discover
      relationships between single-molecule properties and phase boundaries. Here, we
      take advantage of a recently developed coarse-grained framework to calculate the
      theta temperature [Formula: see text], the Boyle temperature [Formula: see text],
      and the critical temperature [Formula: see text] for 20 diverse protein
      sequences, and we show that these three properties are highly correlated. We also
      highlight that these correlations are not specific to our model or simulation
      methodology by comparing between different pairwise potentials and with data from
      other work. We, therefore, suggest that smaller simulations or experiments to
      determine [Formula: see text] or [Formula: see text] can provide useful insights
      into the corresponding phase behavior.

PMID- 30217895
TI  - Contributions of the glycocalyx, endothelium, and extravascular compartment to
      the blood-brain barrier.
AB  - The endothelial cells that form the blood-brain barrier (BBB) are coated with
      glycocalyx, on the luminal side, and with the basement membrane and astrocyte
      endfeet, on the abluminal side. However, it is unclear how exactly the glycocalyx
      and extravascular structures contribute to BBB properties. We used two-photon
      microscopy in anesthetized mice to record passive transport of four different
      sized molecules-sodium fluorescein (376 Da), Alexa Fluor (643 Da), 40-kDa
      dextran, and 150-kDa dextran-from blood to brain, at the level of single cortical
      capillaries. Both fluorescein and Alexa penetrated nearly the entire glycocalyx
      volume, but the dextrans penetrated less than 60% of the volume. This suggested
      that the glycocalyx was a barrier for large but not small molecules. The
      estimated permeability of the endothelium was the same for fluorescein and Alexa
      but several-fold lower for the larger dextrans. In the extravascular compartment,
      co-localized with astrocyte endfeet, diffusion coefficients of the dyes were an
      order of magnitude lower than in the brain parenchyma. This suggested that the
      astrocyte endfeet and basement membrane also contributed to BBB properties. In
      conclusion, the passive transport of small and large hydrophilic molecules
      through the BBB was determined by three separate barriers: the glycocalyx, the
      endothelium, and the extravascular compartment. All three barriers must be taken
      into account in drug delivery studies and when considering BBB dysfunction in
      disease states.

PMID- 30217896
TI  - Interleukin-22 promotes phagolysosomal fusion to induce protection against
      Salmonella enterica Typhimurium in human epithelial cells.
AB  - Intestinal epithelial cells (IECs) play a key role in regulating immune responses
      and controlling infection. However, the direct role of IECs in restricting
      pathogens remains incompletely understood. Here, we provide evidence that IL-22
      primed intestinal organoids derived from healthy human induced pluripotent stem
      cells (hIPSCs) to restrict Salmonella enterica serovar Typhimurium SL1344
      infection. A combination of transcriptomics, bacterial invasion assays, and
      imaging suggests that IL-22-induced antimicrobial activity is driven by increased
      phagolysosomal fusion in IL-22-pretreated cells. The antimicrobial phenotype was
      absent in hIPSCs derived from a patient harboring a homozygous mutation in the
      IL10RB gene that inactivates the IL-22 receptor but was restored by genetically
      complementing the IL10RB deficiency. This study highlights a mechanism through
      which the IL-22 pathway facilitates the human intestinal epithelium to control
      microbial infection.

PMID- 30217897
TI  - Pitfall of big databases.

PMID- 30217898
TI  - Reply to You et al.: The World Database on Protected Areas is an invaluable
      resource for global conservation assessments and planning.

PMID- 30217899
TI  - Renal Fellow Network: Past and Future.

PMID- 30217900
TI  - Substrate-inactivated cyclooxygenase-2 is disposed of by exosomes through the ER
      Golgi pathway.
AB  - Catalysis of arachidonic acid (AA) by cyclooxygenase-2 (COX-2) gives rise to a
      single product that serves as a precursor for all prostaglandins, which are
      central mediators of inflammation. Rapid up-regulation of COX-2 expression in
      response to pro-inflammatory stimuli is a well-characterized means of generating
      the large pool of prostaglandins necessary for inflammation. However, an
      efficient inflammatory process must also terminate rapidly and thus requires
      cessation of COX-2 enzymatic activity and removal of excess protein from the
      cell. Previous studies showed that COX-2 that has not been exposed to AA
      ('naive') degrades in the cellular proteasome. However, continuous exposure to AA
      induces suicide inactivation of COX-2 and its elimination no longer occurs in
      neither the proteasomal nor lysosomal machineries. In the present study, we show
      that either overexpressed or endogenously induced COX-2 is secreted via exosomes
      through the endoplasmic reticulum-Golgi pathway. We further find that excretion
      of COX-2 is significantly enhanced by prolonged exposure to AA. Genetic or
      chemical inhibition of COX-2 enzymatic activity has no effect on its secretion in
      the absence of substrate, but prevents the additional activity-dependent
      secretion. Finally, transfer of COX-2 to target cells only occurs in the absence
      of AA stimulation. Together, these results suggest that exosomal secretion of AA
      activated COX-2 constitutes a means to remove damaged inactive COX-2 from the
      cell.

PMID- 30217901
TI  - Brexit has high stakes for Ireland too.

PMID- 30217902
TI  - Welfare breaches during transport on the up.

PMID- 30217904
TI  - Scottish CVO 'disappointed' with P&O decision.

PMID- 30217906
TI  - Unspecified DNA found in meat samples.

PMID- 30217908
TI  - Sequencing genomes to aid conservation.
AB  - Georgina Mills explains how a research institute is celebrating its 25th birthday
      by sequencing 25 genomes.

PMID- 30217909
TI  - 'Diversity is my number one priority'.
AB  - RCVS president Amanda Boag talks to Josh Loeb about her career in emergency
      critical care and her aims to increase diversity in the profession.

PMID- 30217910
TI  - Antimicrobial resistance in horses.
AB  - Cajsa Isgren and colleagues from the University of Liverpool discuss issues
      around the problem of antimicrobial resistance in bacteria associated with horses
      and introduce a new surveillance initiative.

PMID- 30217911
TI  - Non-surgical embryo transfer technique and recipient mare pregnancy rate.

PMID- 30217912
TI  - What's our role in promoting healthy pet ownership?

PMID- 30217914
TI  - Spreading of bovine TB by hunting hounds.

PMID- 30217915
TI  - Spreading of bovine TB by hunting hounds.

PMID- 30217916
TI  - No evidence to suggest foxhounds spread bovine TB.

PMID- 30217917
TI  - Cascade violations.

PMID- 30217918
TI  - Third party puppy sales.

PMID- 30217919
TI  - Reinventing the wheel?

PMID- 30217924
TI  - Interaction of heat shock protein 70 (HSP70) polymorphisms and occupational
      hazards increases the risk of hypertension in coke oven workers.
AB  - OBJECTIVES: The interaction between genetic, epigenetic inheritance and
      environmental factors determines susceptibility to hypertension. Previous
      epidemiology studies have shown that coke oven workers who are frequently exposed
      to various occupational hazards have remarkable increase in the risk for
      hypertension. Among many genetic variants identified in hypertension, heat shock
      protein 70 (HSP70) was found to play important roles in the pathogenesis of
      hypertension and associated diseases. We therefore explore the possible role of
      HSP70 polymorphisms and their interaction with occupational environment in
      hypertension risk. METHODS: We carried out a case-control study among 367 coke
      oven workers in northwest China, focused on three common HSP70 polymorphisms
      (HSP70-1 G190C, HSP70-2 A1267G and HSP70-hom T2437C), and evaluated the
      association of HSP70 gene polymorphisms with work sites for high risk of
      hypertension. RESULTS: The results indicated that HSP70-1 GC and CC genotype had
      2.73-fold and 4.26-fold increased relative risk (95% CI 1.33 to 5.55 and 1.17 to
      15.53), respectively, comparing with HSP70-1 GG genotype. HSP70-2 AG and GG
      conferred a 47% and 36% reduced risk (95% CI 0.23 to 0.99 and 0.14 to 0.92)
      comparing with HSP70-2 AA genotype. Further analysis of the interaction of HSP70
      polymorphisms with occupational environment indicated a strong positive
      interaction between HSP70 genotype (HSP70-1 GC+CC, HSP70-2 AA and HSP70-hom
      TC+CC) and oven top workplace. CONCLUSIONS: Collectively, these data indicate
      that HSP70 polymorphisms interact with occupational hazards might increase the
      risk of hypertension in coke oven workers.

PMID- 30217925
TI  - Plausibility of the findings reported in 'Prenatal exposure to glycol ethers and
      cryptorchidism and hypospadias: a nested case-control study' by Warembourg et al.

PMID- 30217926
TI  - Concerning the plausibility of the findings reported in 'Prenatal exposure to
      glycol ethers and cryptorchidism and hypospadias: a nested case-control study' by
      Smet and Kelsey: authors' response.

PMID- 30217927
TI  - Long-term exposure to air pollutants from multiple sources and mortality in an
      industrial area: a cohort study.
AB  - BACKGROUND AND AIMS: Residents near industrial areas are exposed to several
      toxins from various sources and the assessment of the health effects is
      difficult. The area of Civitavecchia (Italy) has several sources of environmental
      contamination with potential health effects. We evaluated the association between
      exposure to pollutants from multiple sources and mortality in a cohort of people
      living in the area. METHODS: All residents of the area in 1996 were enrolled
      (from municipal registers) and followed until 2013. Long-term exposures to
      emissions from industrial sources (PM10) and traffic (NOx) at the residential
      addresses were assessed using a dispersion model. Residence close to the harbour
      was also considered. Cox survival analysis was conducted including a linear term
      for industrial PM10 and NOx exposure and a dichotomous variable to indicate
      residence within 500 m of the harbour. Age, sex, calendar period, occupation and
      area-based socioeconomic position (SEP) were considered (HRs, 95% CI). RESULTS:
      71 362 people were enrolled (52% female, 43% low SEP) and 14 844 died during the
      follow-up. We found an association between industrial PM10 and mortality from non
      accidental causes (HR=1.06, 95% CI 1.01 to 1.12), all cancers (HR=1.11, 95% CI
      1.01 to 1.21) and cardiac diseases (HR=1.12, 95% CI 1.01 to 1.23). We also found
      an association between NOx exposure from traffic and mortality from all cancers
      (HR=1.13, 95% CI 1.01 to 1.26) and neurological diseases (HR=1.50, 95% CI 1.01 to
      2.20). Living near the harbour was associated with higher mortality from lung
      cancer (HR=1.31, 95% CI 1.04 to 1.66) and neurological diseases (HR=1.51, 95% CI
      1.05 to 2.18). CONCLUSIONS: Estimated exposures to different pollution sources in
      this area were independently associated with several mortality outcomes while
      adjusting for occupation and socioeconomic status.

PMID- 30217928
TI  - Discovery and Characterization of Dual Inhibitors of MDM2 and NFAT1 for
      Pancreatic Cancer Therapy.
AB  - Overexpression and activation of the murine double minute 2 (MDM2) or nuclear
      factor of activated T cells 1 (NFAT1) oncoproteins frequently occur in pancreatic
      cancer. Most MDM2 inhibitors under development target MDM2-p53 binding and have
      little or no effect on cancers without functional p53, including pancreatic
      cancer. Some available compounds indirectly inhibit NFAT1 activity by interfering
      with calcineurin activity, but there are currently no specific inhibitors against
      NFAT1. Here we performed a high-throughput virtual and cell-based screening to
      yield a lead compound (MA242) that can directly bind both MDM2 and NFAT1 with
      high affinity, induce their protein degradation, and inhibit NFAT1-mediated
      transcription of MDM2 As a result of this binding, MA242 decreased cell
      proliferation and induced apoptosis in pancreatic cancer cell lines regardless of
      p53 status. MA242 alone or in combination with gemcitabine inhibited pancreatic
      tumor growth and metastasis without any host toxicity. Our data indicate that
      targeting both MDM2 and NFAT1 represents a novel and effective strategy to treat
      pancreatic cancer.Significance: These findings suggest that pharmacological
      inhibition of both MDM2 and NFAT1 is a promising strategy for the treatment of
      pancreatic cancer, even in tumors lacking functional p53. Cancer Res; 78(19);
      5656-67. (c)2018 AACR.

PMID- 30217929
TI  - Whole Genome Sequencing Reveals Elevated Tumor Mutational Burden and Initiating
      Driver Mutations in African Men with Treatment-Naive, High-Risk Prostate Cancer.
AB  - African American men are more likely than any other racial group to die from
      prostate cancer. The contribution of acquired genomic variation to this racial
      disparity is largely unknown, as genomic from Africa is lacking. Here we
      performed the first tumor-normal paired deep whole-genome sequencing for Africa.
      A direct study-matched comparison between African- and European-derived,
      treatment-naive, high-risk prostate tumors for 15 cases allowed for further
      comparative analyses of existing data. Excluding a single hyper-mutated tumor
      with 55 mutations per megabase, we observed a 1.8-fold increase in small somatic
      variants in African- versus European-derived tumors (P-value = 1.02e-04), rising
      to 4-fold when compared with published tumor-matched data. Furthermore, we
      observed an increase in oncogenic driver mutations in African tumors (P-value =
      2.92e-03); roughly 30% of impacted genes were novel to prostate cancer, and 79%
      of recurrent driver mutations appeared early in tumorigenesis. Although complex
      genomic rearrangements were less frequent in African tumors, we describe a
      uniquely hyper-duplicated tumor impacting 149 transposable elements. Comparable
      to African Americans, ERG fusions and PIK3CA mutations were absent and PTEN loss
      less frequent. CCND1 and MYC were frequently gained, with somatic copy number
      changes more likely to occur late in tumorigenesis. In addition to traditional
      prostate cancer gene pathways, genes regulating calcium ion-ATPase signal
      transduction were disrupted in African tumors. Although preliminary, our results
      suggest that further validation and investigation into the potential implications
      for elevated tumor mutational burden and tumor-initiating mutations in clinically
      unfavorable prostate cancer can improve patient outcomes in Africa.

PMID- 30217930
TI  - A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk
      with PTEN Signaling.
AB  - The sodium iodide symporter (NIS) is a classical iodide pump typically localized
      within the cell plasma membrane in thyroid cells, where NIS expression is
      believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
      Although radioiodide uptake is generally reduced in thyroid cancer tissue,
      intracellular nonmembranous NIS has been reported to increase, suggesting that
      NIS serves a pump-independent function. Thyroid cancer is one of the major
      component cancers of Cowden syndrome, a subset of which is caused by germline
      mutations in PTEN In this study, we explored the noncanonical tumorigenic role of
      NIS in thyroid cancer cells in relation to PTEN signaling. PTEN knockdown in
      thyroid cancer cell lines stabilized intracellular NIS protein by promoting an
      interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
      Increased protein levels of cytoplasmic NIS enhanced RhoA activation and resulted
      in a promigration tumorigenic phenotype. Inhibition of NIS glycosylation through
      activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization
      of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an
      interaction with LARG, which predominantly localized in the cytoplasm. Moreover,
      PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme
      involved in the initial step of N-linked glycosylation, to inhibit glycosylation
      of NIS. In summary, our results elucidate a pump-independent, protumorigenic role
      for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A
      novel pump-independent protumorigenic role of nonmembranous NIS challenges the
      presumption that radioiodine treatment of thyroid cancer is ineffective when
      transmembrane NIS is not expressed. Cancer Res; 78(21); 6121-33. (c)2018 AACR.

PMID- 30217931
TI  - Association of Albuminuria With Intraglomerular Hydrostatic Pressure and Insulin
      Resistance in Subjects With Impaired Fasting Glucose and/or Impaired Glucose
      Tolerance.
AB  - OBJECTIVE: Little is known about the relationships between insulin resistance,
      intrarenal hemodynamics, and urinary albumin excretion (UAE) in humans with
      impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). The aim
      of the current study was to examine intrarenal hemodynamic abnormalities, insulin
      resistance, and UAE in subjects with IFG or IGT. We hypothesized that intrarenal
      hemodynamic abnormalities would be associated with insulin resistance. RESEARCH
      DESIGN AND METHODS: Fifty-four kidney donors underwent 75-g oral glucose
      tolerance and inulin and para-aminohippuric acid clearance testing. Insulin
      sensitivity index (ISI) was evaluated by the Matsuda index. Intrarenal
      hemodynamic parameters were calculated by the Gomez formulae. RESULTS: Of the 54
      subjects, 33 exhibited IFG or IGT and 31 exhibited normal glucose tolerance
      (NGT). Glomerular hydrostatic pressure (Pglo) and UAE were significantly higher
      in the IFG or IGT subjects with obesity (P = 0.015 and 0.0001, respectively). Log
      ISI correlated significantly and negatively with Pglo (r = -0.351, P = 0.009) in
      all subjects. In multiple regression analyses among all subjects, log ISI was
      associated significantly and independently with Pglo (beta = -0.316, P = 0.015),
      after adjustment for age, sex, and systolic blood pressure. Further, BMI (beta =
      0.517, P = 0.0004), Pglo (beta = 0.420, P = 0.004), and log ISI (beta = -0.366, P
      = 0.008) were each associated significantly and independently with UAE after
      adjustment. CONCLUSIONS: We demonstrated that increased insulin resistance is
      associated with increased Pglo and UAE in IFG or IGT subjects. These hemodynamic
      burdens and insulin resistance may cause injury to the glomeruli even in subjects
      with IFG or IGT.

PMID- 30217932
TI  - Doctors question Hancock's idea of GP video consultations for all.

PMID- 30217933
TI  - Reviewing code consistency is important, but research ethics committees must also
      make a judgement on scientific justification, methodological approach and
      competency of the research team.

PMID- 30217934
TI  - An MRI biomarker of mixed pathology.

PMID- 30217935
TI  - Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer
      disease.
AB  - OBJECTIVE: To assess the onset, sequence, and rate of progression of
      comprehensive biomarker and clinical measures across the spectrum of Alzheimer
      disease (AD) using the Dominantly Inherited Alzheimer Network (DIAN) study and
      compare these to cross-sectional estimates. METHODS: We conducted longitudinal
      clinical, cognitive, CSF, and neuroimaging assessments (mean of 2.7 [+/-1.1]
      visits) in 217 DIAN participants. Linear mixed effects models were used to assess
      changes in each measure relative to individuals' estimated years to symptom onset
      and to compare mutation carriers and noncarriers. RESULTS: Longitudinal beta
      amyloid measures changed first (starting 25 years before estimated symptom
      onset), followed by declines in measures of cortical metabolism (approximately 7
      10 years later), then cognition and hippocampal atrophy (approximately 20 years
      later). There were significant differences in the estimates of CSF p-tau181 and
      tau, with elevations from cross-sectional estimates preceding longitudinal
      estimates by over 10 years; further, longitudinal estimates identified a
      significant decline in CSF p-tau181 near symptom onset as opposed to continued
      elevations. CONCLUSION: These longitudinal estimates clarify the sequence and
      temporal dynamics of presymptomatic pathologic changes in autosomal dominant AD,
      information critical to a better understanding of the disease. The pattern of
      biomarker changes identified here also suggests that once beta-amyloidosis
      begins, additional pathologies may begin to develop less than 10 years later, but
      more than 15 years before symptom onset, an important consideration for
      interventions meant to alter the disease course.

PMID- 30217936
TI  - An MRI measure of degenerative and cerebrovascular pathology in Alzheimer
      disease.
AB  - OBJECTIVE: To develop, replicate, and validate an MRI-based quantitative measure
      of both cerebrovascular and neurodegeneration in Alzheimer disease (AD) for
      clinical and potentially research purposes. METHODS: We used data from a cross
      sectional and longitudinal community-based study of Medicare-eligible residents
      in northern Manhattan followed every 18-24 months (n = 1,175, mean age 78 years).
      White matter hyperintensities, infarcts, hippocampal volumes, and cortical
      thicknesses were quantified from MRI and combined to generate an MRI measure
      associated with episodic memory. The combined MRI measure was replicated and
      validated using autopsy data, clinical diagnoses, and CSF biomarkers and amyloid
      PET from the Alzheimer's Disease Neuroimaging Initiative. RESULTS: The
      quantitative MRI measure was developed in a group of community participants (n =
      690) and replicated in a similar second group (n = 485). Compared with healthy
      controls, the quantitative MRI measure was lower in patients with mild cognitive
      impairment and lower still in those with clinically diagnosed AD. The
      quantitative MRI measure correlated with neurofibrillary tangles, neuronal loss,
      atrophy, and infarcts at postmortem in an autopsy subset and was also associated
      with PET amyloid imaging and CSF levels of total tau, phosphorylated tau, and
      beta-amyloid 42. The MRI measure predicted conversion to MCI and clinical AD
      among healthy controls. CONCLUSION: We developed, replicated, and validated an
      MRI measure of cerebrovascular and neurodegenerative pathologies that are
      associated with clinical and neuropathologic diagnosis of AD and related to
      established biomarkers.

PMID- 30217938
TI  - NfL is a biomarker for adult-onset leukoencephalopathy with axonal spheroids and
      pigmented glia.

PMID- 30217937
TI  - Serum neurofilament light: A biomarker of neuroaxonal injury after ischemic
      stroke.
AB  - OBJECTIVE: To explore the utility of serum neurofilament light chain (NfL) as a
      biomarker for primary and secondary neuroaxonal injury after ischemic stroke (IS)
      and study its value for the prediction of clinical outcome. METHODS: We used an
      ultrasensitive single-molecule array assay to measure serum NfL levels in healthy
      controls (n = 30) and 2 independent cohorts of patients with IS: (1) with serial
      serum sampling at hospital arrival (n = 196), at days 2, 3, and 7 (n = 89), and
      up to 6 months post stroke; and (2) with standardized MRI at baseline and at 6
      months post stroke, and with cross-sectional serum sampling at 6 months (n = 95).
      We determined the temporal profile of serum NfL levels, their association with
      imaging markers of neuroaxonal injury, and with clinical outcome. RESULTS:
      Patients with IS had higher serum NfL levels compared with healthy controls
      starting from admission until 6 months post stroke. Serum NfL levels peaked at
      day 7 (211.2 pg/mL [104.7-442.6], median [IQR]) and correlated with infarct
      volumes (day 7: partial r = 0.736, p = 1.5 * 10-15). Six months post stroke,
      patients with recurrent ischemic lesions on MRI (n = 19) had higher serum NfL
      levels compared to those without new lesions (n = 76, p = 0.002). Serum NfL
      levels 6 months post stroke further correlated with a quantitative measure of
      secondary neurodegeneration obtained from diffusion tensor imaging MRI (r =
      0.361, p = 0.001). Serum NfL levels 7 days post stroke independently predicted
      modified Rankin Scale scores 3 months post stroke (cumulative odds ratio [95%
      confidence interval] = 2.35 [1.60-3.45]; p = 1.24 * 10-05). CONCLUSION: Serum NfL
      holds promise as a biomarker for monitoring primary and secondary neuroaxonal
      injury after IS and for predicting functional outcome.

PMID- 30217939
TI  - Chorea, psychosis, acanthocytosis, and prolonged survival associated with ELAC2
      mutations.

PMID- 30217940
TI  - Timing of milestone competency acquisition in neurology residency: What by when?
AB  - OBJECTIVE: To determine the stage of training at which neurology residents should
      achieve individual elements of the Accreditation Council for Graduate Medical
      Education neurology Milestones and to examine the relationship between perceived
      importance of Milestones and the stage by which they should be achieved. METHODS:
      A modified Delphi technique was used to establish consensus postgraduate year
      (PGY) expectations for neurology Milestone competencies across 3 geographically
      and administratively distinct Mayo Clinic neurology residency programs. Timing
      expectations were examined for relationships to perceived importance of the
      individual Milestones and effects of participant characteristics. RESULTS: PGY
      expectations for neurology Milestone elements ranged from PGY 1.3 to PGY 4.1.
      Extent of rater educational seniority had no effect on PGY competency
      expectations. There was a moderate inverse relationship between perceived
      importance of the Milestone element and the PGY by which it should be achieved (r
      s = -0.74, p < 0.0001). CONCLUSIONS AND RELEVANCE: Expectations for neurology
      Milestone competency acquisition can be measured and may help inform individual
      program design, educational expectations, and future Milestone design.

PMID- 30217941
TI  - Nutritional aspects of cannibalism and other pieces of odd research win Ig Nobel
      prizes.

PMID- 30217942
TI  - Sevoflurane relieves hepatic ischemia-reperfusion injury by inhibiting the
      expression of Grp78.
AB  - Purpose: This article aimed to study the role of sevoflurane pre-conditioning in
      hepatic ischemia-reperfusion and its potential mechanism.Methods: Rat liver
      ischemia-reperfusion model was constructed. Serum TNF-alpha, IL-1beta, IL-10, and
      IL-6 concentrations were detected by ELISA. Malondialdehyde (MDA), superoxide
      dismutase (SOD), and nitric oxide (NO) in liver homogenate were determined.
      Hematoxylin-Eosin (HE) staining, Tunel, and immunohistochemistry were performed.
      Ischemia-reperfusion hepatocyte model was established. Cells transfection was
      conducted. Apoptosis was observed by flow cytometry. Quantitative real-time PCR
      (qRT-PCR) and Western blotting analysis were used.Results: Compared with I/R
      group, liver damage degree, liver cell apoptosis, and glucose regulatory protein
      78 (Grp78) expression was obviously reduced in rats of SEV group. TNF-alpha, IL
      1beta, and IL-6 concentrations were also significantly increased (P<0.01). MDA
      and NO concentrations were dramatically lower (P<0.01) and SOD concentration was
      significantly higher (P<0.01). Apoptosis rate, Grp78, PERK, eIF2alpha, and p-c
      JNK/JNK expression was also significantly decreased (P<0.01). Sevoflurane
      significantly reduced apoptosis and expression of PERK, eIF2alpha, p-c-JNK/JNK by
      inhibiting the expression of Grp78 (P<0.01).Conclusion: Sevoflurane relieves
      hepatic ischemia-reperfusion injury by inhibiting the expression of Grp78.

PMID- 30217943
TI  - N-Acetylcysteine inhalation improves pulmonary function in patients received
      liver transplantation.
AB  - Postoperative pulmonary complications (PPCs) following orthotopic liver
      transplantation (OLT) are associated with high morbidity and mortality rates. The
      effect of N-acetylcysteine (NAC) inhalation on the incidence of PPCs and the
      outcomes of patients undergoing OLT is unknown. This prospective randomized
      controlled clinical trial was conducted to investigate the effect of NAC
      inhalation during OLT on PPCs. Sixty patients were randomly assigned to the NAC
      group (n = 30) or the control group (n = 30) to receive inhaled NAC or sterilized
      water, respectively, for 30 min before surgery and 3 h after reperfusion. The
      incidence of early PPCs and outcomes including survival rate were assessed.
      Biomarkers including tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, Clara
      cell secretory protein (CC16), intercellular adhesion molecule (ICAM)-1, and
      superoxide dismutase (SOD) were measured in exhaled breath condensate (EBC) at T1
      (before surgery) and T2 (at the end of operation) as well as in serum at T1, T2,
      T3 (12 h after operation), and T4 (24 h after operation). A total of 42 patients
      (20 in the NAC group and 22 in the control group) were enrolled in the final
      analysis. Atomization inhaled NAC significantly reduced the incidence of PPCs
      after OLT. The levels of TNF-alpha, IL-8, CC16, and ICAM-1 in EBC were
      significantly lower, and SOD activity was higher, at T2 in the NAC group; similar
      data were found in serum at T2, T3, and T4. In summary, perioperative NAC
      inhalation may reduce the incidence of PPCs and improve patient outcomes after
      OLT.

PMID- 30217944
TI  - The regulatory roles of lncRNAs in the process of breast cancer invasion and
      metastasis.
AB  - Breast cancer (BC) is the most common cancer and principal cause of death among
      females worldwide. Invasion and metastasis are major causes which influence the
      survival and prognosis of BC. Therefore, to understand the molecule mechanism
      underlying invasion and metastasis is paramount for developing strategies to
      improve survival and prognosis in BC patients. Recent studies have reported that
      long non-coding RNAs (lncRNAs) play critical roles in the regulation of BC
      invasion and metastasis through a variety of molecule mechanisms that endow cells
      with an aggressive phenotype. In this article, we focused on the function of
      lncRNAs on BC invasion and metastasis through participating in epithelial-to
      mesenchymal transition, strengthening cancer stem cells generation, serving as
      competing endogenous lncRNAs, influencing multiple signaling pathways as well as
      regulating expressions of invasion-metastasis related factors, including cells
      adhesion molecules, extracellular matrix, and matrix metallo-proteinases. The
      published work described has provided a better understanding of the mechanisms
      underpinning the contribution of lncRNAs to BC invasion and metastasis, which may
      lay the foundation for the development of new strategies to prevent BC invasion
      and metastasis.

PMID- 30217945
TI  - Preventive effect of artemisinin extract against cholestasis induced via
      lithocholic acid exposure.
AB  - Obstructive cholestasis characterized by biliary pressure increase leading to
      leakage of bile back that causes liver injury. The present study aims to evaluate
      the effects of artemisinin in obstructive cholestasis in mice. The present study
      was carried out on 40 adult healthy mice that were divided into 4 groups, 10 mice
      each; the negative control group didn't receive any medication. The normal group
      was fed normally with 100 mg/kg of artemisinin extract orally. The cholestatic
      group fed on 1% lithocholic acid (LCA) mixed into control diet and cholestatic
      group co-treated with 100 mg/kg of artemisinin extract orally. Mice were treated
      for 1 month then killed at end of the experiment. A significant increase in
      alanine aminotransferase, aspartate aminotransferase, and total and direct
      bilirubin was detected in mice exposed to LCA toxicity. That increase was
      significantly reduced to normal values in mice co-treated with artemisinin. LCA
      toxicity causes multiple areas of necrosis of irregular distribution. However,
      artemisinin co-treatment showed normal hepatic architecture. Moreover, LCA causes
      down-regulation of hepatic mRNA expressions of a set of genes that are
      responsible for ATP binding cassette and anions permeability as ATP-binding
      cassette sub-family G member 8, organic anion-transporting polypeptide, and
      multidrug resistance-associated protein 2 genes that were ameliorated by
      artemisinin administration. Similarly, LCA toxicity significantly down-regulated
      hepatic mRNA expression of constitutive androstane receptor, OATP4, and farnesoid
      x receptor genes. However, artemisinin treatment showed a reasonable prevention.
      In conclusion, the current study strikingly revealed that artemisinin treatment
      can prevent severe hepatotoxicity and cholestasis that led via LCA exposure.

PMID- 30217946
TI  - Association of brain natriuretic peptide gene polymorphisms with chronic
      obstructive pulmonary disease complicated with pulmonary hypertension and its
      mechanism.
AB  - Objective: To examine the association between brain natriuretic peptide (BNP)
      gene single nucleotide polymorphisms (SNPs) and chronic obstructive pulmonary
      disease (COPD) and COPD with pulmonary hypertension (PH) and to analyze its
      mechanism. Methods: The genotypes of BNP at the rs198389, rs6668352, and rs198388
      loci in 339 patients with COPD (205 in the COPD/PH- group and 134 in the COPD/PH+
      group) and 125 healthy subjects were detected by PCR/Sanger sequencing. The serum
      levels of BNP, fibrinogen (Fbg), and Apelin were measured in all subjects by
      ELISA. Results: The BNP rs198389 locus G allele, rs6668352 locus A allele, and
      198388 locus T allele were high risk factors for COPD (P<0.001). Logistics
      regression analysis showed that BNP rs198389 locus G allele, rs6668352 locus A
      allele, and rs198388 locus T allele were high risk factors for PH in COPD
      patients (all P<0.001). The levels of the serum BNP and Fbg protein in the
      control group, COPD/PH- group, and COPD/PH+ group increased successively, and the
      expression levels of Apelin protein decreased successively (all P<0.001). The BNP
      and Fbg protein levels in the wild-type, heterozygote, and mutant homozygote in
      BNP rs198389, rs6668352, and rs198388 loci increased successively, and the serum
      Apelin protein levels decreased successively (all P<0.001). Conclusion: The
      polymorphisms of BNP at the rs198389, rs6668352, and rs198388 loci are associated
      with the occurrence of COPD and COPD with PH, and the occurrence may be related
      to the abnormal expression level of BNP, Fbg, and Apelin protein in the serum.

PMID- 30217948
TI  - Cochrane HPV vaccine review: BMJ journal defends "inconvenient criticisms".

PMID- 30217947
TI  - HADC regulates the diabetic vascular endothelial dysfunction by targetting MnSOD.
AB  - Vascular dysfunction is a common result of diabetes in humans. However, the
      mechanism underlying diabetic vascular dysfunction is not fully understood. Here
      in the present study, we showed that the histone deacetylase 2 (HDAC2) promoted
      the endothelial dysfunction induced by diabetes. The expression and activity of
      HDAC2 were up-regulated in vascular endothelial cells (ECs) from diabetic
      patients and mice. The expression of HDAC2 was also increased by high glucose
      stress in isolated human ECs. HDAC2 knockdown repressed the proliferation rate
      and promoted high glucose-induced apoptosis of ECs, which was associated with the
      activation of apoptotic pathways (Bcl-2, Caspase 3, and Bax). By contrast, HDAC2
      overexpression led to opposing results. Significantly, we observed that HDAC2
      regulated the accumulation of reactive oxygen species (ROS) induced by high
      glucose in ECs, which accounted for the effects of HDAC2 on proliferation and
      apoptosis because antioxidants, N-acetyl-l-cysteine (NAC) or MnTBAP treatment
      blocked the effects of HDAC2 on apoptosis of ECs under high glucose condition.
      Mechanism study revealed that HDAC2 bound to the promoter of MnSOD and repressed
      the expression of MnSOD by regulating the level of acetylated H3K9 and H3K27,
      which led to the promotion of oxidative stress and contributed to the function of
      HDAC2 in ECs under high glucose condition. Altogether, our evidence demonstrated
      that HDAC2-MnSOD signaling was critical in oxidative stress and proliferation as
      well as the survival of ECs under high glucose condition.

PMID- 30217949
TI  - Flu vaccination: Toronto hospitals cannot implement staff "vaccinate or mask"
      policy, says ruling.

PMID- 30217950
TI  - Functional Proteomics and Deep Network Interrogation Reveal a Complex Mechanism
      of Action of Midostaurin in Lung Cancer Cells.
AB  - Lung cancer is associated with high prevalence and mortality, and despite
      significant successes with targeted drugs in genomically defined subsets of lung
      cancer and immunotherapy, the majority of patients currently does not benefit
      from these therapies. Through a targeted drug screen, we found the recently
      approved multi-kinase inhibitor midostaurin to have potent activity in several
      lung cancer cells independent of its intended target, PKC, or a specific genomic
      marker. To determine the underlying mechanism of action we applied a layered
      functional proteomics approach and a new data integration method. Using chemical
      proteomics, we identified multiple midostaurin kinase targets in these cells.
      Network-based integration of these targets with quantitative tyrosine and global
      phosphoproteomics data using protein-protein interactions from the STRING
      database suggested multiple targets are relevant for the mode of action of
      midostaurin. Subsequent functional validation using RNA interference and
      selective small molecule probes showed that simultaneous inhibition of TBK1,
      PDPK1 and AURKA was required to elicit midostaurin's cellular effects. Immunoblot
      analysis of downstream signaling nodes showed that combined inhibition of these
      targets altered PI3K/AKT and cell cycle signaling pathways that in part converged
      on PLK1. Furthermore, rational combination of midostaurin with the potent PLK1
      inhibitor BI2536 elicited strong synergy. Our results demonstrate that
      combination of complementary functional proteomics approaches and subsequent
      network-based data integration can reveal novel insight into the complex mode of
      action of multi-kinase inhibitors, actionable targets for drug discovery and
      cancer vulnerabilities. Finally, we illustrate how this knowledge can be used for
      the rational design of synergistic drug combinations with high potential for
      clinical translation.

PMID- 30217951
TI  - Do all HEART Scores beat the same: evaluating the interoperator reliability of
      the HEART Score.
AB  - BACKGROUND: Patients presenting with chest pain represent a significant
      proportion of attendances to the ED. The History, ECG, Age, Risk Factors and
      Troponin (HEART) Score is validated for the risk stratification of suspected
      ischaemic chest pain within the ED. The goal of this research was to establish
      the interoperator reliability of the HEART Score as performed in the ED by
      different grades of doctor and nurse. METHODOLOGY: Patients with suspected
      ischaemic chest pain presenting to the ED of an inner city, London Hospital, were
      recruited prospectively between January and May 2016. Patients that had been
      enrolled in the study were interviewed by clinicians from four different
      categories: senior doctor, junior doctor, senior nurse and junior nurse.
      Clinicians, blinded to other raters' results, calculated the HEART Scores for
      each patient with the assistance of a pocket-sized HEART Score card. The
      intraclass correlation coefficient (ICC) was calculated as the primary measure of
      reliability. 120 patients were required to achieve a desired power of 80%.
      RESULTS: 88 complete comparisons were obtained. There were no significant
      differences between the distributions of HEART Scores for each clinician group
      (p=0.95). The ICC for the overall HEART Score was 0.91 (95% CI 0.87 to 0.93). The
      ICC for troponin and age were '1', for 'history' 0.41 (95% CI 0.30 to 0.52),
      'ECG' 0.64 (95% CI 0.54 to0.73) and 'risk factors' 0.84 (95% CI 0.79 to 0.89).
      CONCLUSION: This study demonstrates very strong overall interoperator reliability
      between the four groups of clinicians studied. This suggests that the HEART Score
      is reproducible when used by different professional groups and grade of
      clinician.

PMID- 30217952
TI  - Systematic review and meta-analysis of pre-hospital diagnostic accuracy studies.
AB  - INTRODUCTION: Paramedics are involved in examining, treating and diagnosing
      patients. The accuracy of these diagnoses is evaluated using diagnostic accuracy
      studies. We undertook a systematic review of published literature to provide an
      overview of how accurately paramedics diagnose patients compared with hospital
      doctors. A bivariate meta-analysis was incorporated to examine the range of
      diagnostic sensitivity and specificity. METHODS: We searched MEDLINE, CINAHL,
      Embase, AMED and the Cochrane Database from 1946 to 7 May 2016 for studies where
      patients had been given a diagnosis by paramedics and hospital doctors. Keywords
      focused on study type ('diagnostic accuracy'), outcomes (sensitivity,
      specificity, likelihood ratio?, predictive value?) and setting (paramedic*, pre
      hospital, ambulance, 'emergency service?', 'emergency medical service?',
      'emergency technician?'). RESULTS: 2941 references were screened by title and/or
      abstract. Eleven studies encompassing 384 985 patients were included after full
      text review. The types of diagnoses in one of the studies encompassed all
      possible diagnoses and in the other studies focused on sepsis, stroke and
      myocardial infarction. Sensitivity estimates ranged from 32% to 100% and
      specificity estimates from 14% to 100%. Eight of the studies were deemed to have
      a low risk of bias and were incorporated into a meta-analysis which showed a
      pooled sensitivity of 0.74 (0.62 to 0.82) and a pooled specificity of 0.94 (0.87
      to 0.97). DISCUSSION: Current published research suggests that diagnoses made by
      paramedics have high sensitivity and even higher specificity. However, the
      paucity and varying quality of studies indicates that further prehospital
      diagnostic accuracy studies are warranted especially in the field of non-life
      threatening conditions. PROSPERO REGISTRATION NUMBER: CRD42016039306.

PMID- 30217953
TI  - Alleviating mechanical constraints to ventilation with heliox improves exercise
      endurance in adult survivors of very preterm birth.
AB  - Adult survivors of very preterm birth (PRET) have significantly lower aerobic
      exercise capacities than their counterparts born at term (CONT), but the
      underlying cause is unknown. To test whether expiratory flow limitation (EFL)
      during exercise negatively affects exercise endurance in PRET, we had PRET and
      CONT exercise to exhaustion breathing air and again breathing heliox. In PRET,
      EFL decreased and time-to-exhaustion increased significantly while breathing
      heliox. Heliox had a minimal effect on EFL and had no effect on time-to
      exhaustion in CONT. We conclude that aerobic exercise endurance in PRET is
      limited, in part, by mechanical ventilatory constraints, specifically EFL.

PMID- 30217956
TI  - The superior oblique muscle and its disorders.

PMID- 30217955
TI  - CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt
      signalling.
AB  - Uncontrolled cell division is a hallmark of cancer. Deregulation of Wnt
      components has been linked to aberrant cell division by multiple mechanisms,
      including Wnt-mediated stabilisation of proteins signalling, which was notably
      observed in mitosis. Analysis of Wnt components revealed an unexpected role of B
      cell CLL/lymphoma 9 (BCL9) in maintaining mitotic Wnt signalling to promote
      precise cell division and growth of cancer cell. Mitotic interactome analysis
      revealed a mechanistic role of BCL9 in inhibiting clathrin-mediated degradation
      of LRP6 signalosome components by interacting with clathrin and the components in
      Wnt destruction complex; this function was further controlled by CDK1-driven
      phosphorylation of BCL9 N-terminal, especially T172. Interestingly, T172
      phosphorylation was correlated with cancer patient prognosis and enriched in
      tumours. Thus, our results revealed a novel role of BCL9 in controlling mitotic
      Wnt signalling to promote cell division and growth.

PMID- 30217954
TI  - Proteins that control the geometry of microtubules at the ends of cilia.
AB  - Cilia, essential motile and sensory organelles, have several compartments: the
      basal body, transition zone, and the middle and distal axoneme segments. The
      distal segment accommodates key functions, including cilium assembly and sensory
      activities. While the middle segment contains doublet microtubules (incomplete B
      tubules fused to complete A-tubules), the distal segment contains only A-tubule
      extensions, and its existence requires coordination of microtubule length at the
      nanometer scale. We show that three conserved proteins, two of which are mutated
      in the ciliopathy Joubert syndrome, determine the geometry of the distal segment,
      by controlling the positions of specific microtubule ends. FAP256/CEP104 promotes
      A-tubule elongation. CHE-12/Crescerin and ARMC9 act as positive and negative
      regulators of B-tubule length, respectively. We show that defects in the distal
      segment dimensions are associated with motile and sensory deficiencies of cilia.
      Our observations suggest that abnormalities in distal segment organization cause
      a subset of Joubert syndrome cases.

PMID- 30217957
TI  - DS-8500a, an Orally Available G Protein-Coupled Receptor 119 Agonist, Upregulates
      Glucagon-Like Peptide-1 and Enhances Glucose-Dependent Insulin Secretion and
      Improves Glucose Homeostasis in Type 2 Diabetic Rats.
AB  - G protein-coupled receptor 119 (GPR119) has been shown to be highly expressed in
      small intestinal L-cells and pancreatic beta-cells and mediates intracellular
      cAMP concentration, glucagon-like peptide (GLP-1) secretion, and glucose
      stimulated insulin secretion (GSIS). This study examined the pharmacological
      effects of 4-(5-{(1R)-1-[4-(cyclopropylcarbonyl) phenoxy]propyl}-1,2,4-oxadiazol
      3-yl)-2-fluoro-N-[(2R)-1-hydroxypropan-2-yl]benzamide (DS-8500a), a novel, orally
      available, selective GPR119 agonist. In in vitro studies, DS-8500a increased
      intracellular cAMP in a concentration-dependent manner in human, rat, and mouse
      GPR119-expressing Chinese hamster ovary (CHO)-K1 cells, with EC50 values of 51.5,
      98.4, and 108.1 nmol/l, respectively. DS-8500a had no effect on intracellular
      cAMP in pcDNA3.1/CHO-K1 cells. In in vivo studies, DS-8500a augmented plasma GLP
      1 concentration in Zucker fatty (ZF) rats, and enhanced GSIS and did not change
      plasma glucose concentration in fasted Sprague-Dawley (SD) rats. A single dose of
      DS-8500a showed dose-dependent glucose-lowering effects at oral glucose tolerance
      test (OGTT) in ZF rats. In a repeat-dosing study, DS-8500a had statistically
      significant glucose-lowering effects at OGTT performed at the 1st day and after 2
      weeks of treatment in neonatal streptozotocin-treated (nSTZ) rats, and the
      efficacy levels of DS-8500a in each test were greater than those of GSK1292263 or
      MBX-2982, which had been clinically tested previously as GPR119 agonists. Through
      pharmacokinetics and pharmacodynamics assessment, the high intrinsic activity of
      DS-8500a was suggested to be one of the reasons for the greater glucose lowering
      effect in the nSTZ rats. DS-8500a is a useful compound among GPR119 agonists that
      can maximize the potential benefit of GPR119 in type 2 diabetes.

PMID- 30217958
TI  - A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To
      Investigate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Repeat
      Doses of Inhaled Nemiralisib in Adults with Persistent, Uncontrolled Asthma.
AB  - Phosphoinositide 3-kinase delta (PI3Kdelta) is a lipid kinase involved in
      leukocyte recruitment and activation. Activation of PI3Kdelta has been linked to
      airway inflammation and asthma pathogenesis. This randomized, double-blind,
      placebo-controlled, crossover study investigated the efficacy, safety,
      tolerability, and pharmacokinetics of a PI3Kdelta inhibitor, nemiralisib
      (GSK2269557), in patients with persistent, uncontrolled asthma. Patients (n = 50)
      received once-daily inhaled nemiralisib (1000 ug) or placebo for 28 days, with a
      crossover to the alternative treatment following a 4-week washout period.
      Spirometry demonstrated no discernible difference in trough forced expiratory
      volume in 1 second (FEV1) from baseline (adjusted posterior median 7 ml; 95%
      credible interval -83, 102 ml) between nemiralisib and placebo treatment at day
      28 (primary endpoint). These results were supported by most secondary endpoints,
      including weighted mean FEV1 (0-4 hours) and change in trough forced vital
      capacity at day 28. Nemiralisib was generally well-tolerated, with few side
      effects except for post-inhalation cough (nemiralisib: 35%; placebo: 9%). At day
      14, sputum interleukin (IL)-5, IL-13, IL-6, and IL-8 levels were reduced by a
      median of 17%, 7%, 15%, and 8%, respectively, when comparing nemiralisib with
      placebo [n = 15 (IL-5, IL-8) or 16 (IL-6, IL-13); posterior probability of a true
      ratio >0%: 78%, 64%, 76%, and 63%, respectively]. These results suggest that
      nemiralisib inhibited PI3Kdelta locally; however, this did not translate into
      meaningful clinical improvement. Further studies will investigate the potential
      efficacy of nemiralisib in patients with asthma with other specific more severe
      phenotypes, including those who are colonized with bacteria and frequently
      exacerbate.

PMID- 30217959
TI  - Inclusion of LGBTQ persons in research related to pregnancy risk: a cognitive
      interview study.
AB  - INTRODUCTION: Recently, researchers have begun considering whether and how to
      include lesbian, gay, bisexual, transgender and queer (LGBTQ) people in research
      about abortion and contraception care. Including LGBTQ people in research about
      abortion and contraception care, as well as the risk for unintended pregnancy
      more broadly, requires accurate assessment of risk for unintended pregnancy,
      which involves different considerations for LGBTQ people. METHODS: We created a
      survey with existing sexual orientation and gender identity measures, new
      reproductive anatomy questions to guide skip patterns, gender neutral terminology
      in sexual and behavioural risk questions, and existing contraception and
      pregnancy intentions questions that were modified to be gender neutral. We then
      assessed the appropriateness of these measures through cognitive interviews with
      39 individuals aged 18-44 years who were assigned female at birth and identified
      as LGBTQ. Participants were recruited in the San Francisco Bay Area of
      California, Baltimore, Maryland and other cities. RESULTS: Existing demographic
      questions on sexual orientation and gender identity were well received by
      participants and validating of participant reported identities. Participants
      responded positively to new reproductive anatomy questions and to gender neutral
      terminology in sexual behaviour and pregnancy risk questions. They felt skip
      patterns appropriately removed them out of inappropriate items (eg, use of
      contraception to avoid unintended pregnancy); there was some question about
      whether pregnancy intention measures were widely appropriate or should be further
      restricted. CONCLUSIONS: This study provides guidance on ways to appropriately
      evaluate inclusion of LGBTQ people in abortion and contraception research.

PMID- 30217960
TI  - Flavour capsule heat-sticks for heated tobacco products.

PMID- 30217961
TI  - WHO FCTC and global governance: effects and implications for future global public
      health instruments.
AB  - INTRODUCTION: This article analyses experience with the WHO Framework Convention
      on Tobacco Control (WHO FCTC) in the context of global governance. It examines
      ways in which the WHO FCTC has been addressed by international institutions,
      particularly within the UN system at the international and national levels. It
      seeks to understand the extent to which the WHO FCTC as an international legal
      obligation has contributed to its integration in the strategies, policies and
      programmes of UN system organisations. METHODS: The article examines
      documentation reflecting global governance responses to tobacco control since the
      Convention's entry into force in 2005. It also considers discussions with
      officials involved in the design and management of various UN initiatives.
      Finally, it draws on the findings of the Expert Group on the Impact Assessment of
      the WHO FCTC. CONCLUSIONS: The influence of the WHO FCTC in global governance can
      be at least partially attributed to its status as an international legal
      obligation. While tobacco control would have likely been a priority in
      international public health even in the absence of the WHO FCTC, the importance
      of tobacco control has been relatively greater as a result of the treaty. In
      assessing the potential utility of any future global public health instrument, it
      is important to consider the need to mobilise action by other global governance
      institutions and ensure that the chosen instrument will be capable of stimulating
      such action.

PMID- 30217962
TI  - PDAC Can Arise from PanINs via Multiple Evolutionary Routes.
AB  - Phylogenetic analysis of PanINs and PDACs reveals evolutionary relationships
      between coexisting lesions.

PMID- 30217964
TI  - Multiplexed Imaging Characterizes the Tumor-Immune Microenvironment.
AB  - TNBCs could be characterized as immune cold, compartmentalized, or mixed based on
      immune infiltration.

PMID- 30217963
TI  - TXNIP-Dependent Extracellular Matrix Remodeling Drives Glycolysis.
AB  - Remodeling of the extracellular matrix promotes glycolysis-dependent breast
      cancer migration.

PMID- 30217965
TI  - Illuminating Aberrant mRNA Events in CLL.
AB  - Findings from a recent study suggest that intronic polyadenylation, a form of
      mRNA processing, is aberrant and widespread in chronic lymphocytic leukemia,
      targeting multiple genes. This results in truncated proteins that no longer
      function as effective tumor suppressors and, in some cases, are even oncogenic.

PMID- 30217966
TI  - Primary Tumor Driver Mutations Also Drive Metastases.
AB  - The large majority of driver mutations were shared within all metastases from
      each patient.

PMID- 30217967
TI  - PLK1 Inhibition Targets Myc-Activated Malignant Glioma Cells Irrespective of
      Mismatch Repair Deficiency-Mediated Acquired Resistance to Temozolomide.
AB  - Mismatch repair (MMR) deficiency through MSH6 inactivation has been identified in
      up to 30% of recurrent high-grade gliomas, and represents a key molecular
      mechanism underlying the acquired resistance to the alkylating agent temozolomide
      (TMZ). To develop a therapeutic strategy that could be effective in these TMZ
      refractory gliomas, we first screened 13 DNA damage response modulators for their
      ability to suppress viability of MSH6-inactivated, TMZ-resistant glioma cells. We
      identified a PLK1 selective inhibitor, Volasertib, as the most potent in
      inhibiting proliferation of glioblastoma cells. PLK1 inhibition induced mitotic
      catastrophe, G2-M cell-cycle arrest, and DNA damage, leading to caspase-mediated
      apoptosis in glioblastoma cells. Importantly, therapeutic effects of PLK1
      inhibitors were not influenced by MSH6 knockdown, indicating that their action is
      independent of MMR status of the cells. Systemic treatment with Volasertib
      potently inhibited tumor growth in an MMR-deficient, TMZ-resistant glioblastoma
      xenograft model. Further in vitro testing in established and patient-derived cell
      line panels revealed an association of PLK1 inhibitor efficacy with cellular Myc
      expression status. We found that cells with deregulated Myc are vulnerable to
      PLK1 inhibition, as Myc overexpression sensitizes, whereas its silencing
      desensitizes, glioblastoma cells to PLK1 inhibitors. This discovery is clinically
      relevant as glioma progression post-TMZ treatment is frequently accompanied by
      MYC genomic amplification and/or pathway activation. In conclusion, PLK inhibitor
      represents a novel therapeutic option for recurrent gliomas, including those TMZ
      resistant from MMR deficiency. Genomic MYC alteration may serve as a biomarker
      for PLK inhibitor sensitivity, as Myc-driven tumors demonstrated pronounced
      responses.

PMID- 30217968
TI  - Laparoscopic Trans-Abdominal Right Adrenalectomy for a Large Primitive Adrenal
      Oncocytic Carcinoma: A Case Report and Review of Literature.
AB  - BACKGROUND Adrenocortical oncocytic neoplasms (AONs) are extremely rare tumors.
      AONs are classified as: oncocytoma (AO), oncocytic neoplasm of uncertain
      malignant potential (AONUMP), and oncocytic carcinoma (AOC). Among the 162
      reported cases of AONs in the literature, 30 cases were classified as malignant.
      Adrenalectomy is the treatment of choice for AON. CASE REPORT We report the case
      of a 48-year-old man with a primitive 12-cm mass affecting the right adrenal
      gland, detected by ultrasonography during follow-up for alcoholic liver
      cirrhosis. Computed tomography (CT) scan and magnetic resonance imaging (MRI)
      showed a mass of the right adrenal gland compressing the inferior vena cava (IVC)
      and dislocating the right lobe of the liver, with no invasion of kidney, liver,
      or IVC. Preoperative blood tests showed mild transaminase increase. Laparoscopic
      right adrenalectomy with lateral transperitoneal approach was performed. The
      postoperative course was uneventful. The lesion was diagnosed as a primitive
      adrenal oncocytic carcinoma (AOC). No recurrence was evidenced during 24-month
      follow-up. CONCLUSIONS Although AONs are very rare, they must be considered in
      the differential diagnosis of adrenal masses due to their prognostic difference
      compared to non-oncocytic tumors. AOCs are a rare presentation of AONs. Only 30
      cases are described in the literature. Laparotomic adrenalectomy is the treatment
      of choice for AOC. We report the first case of laparoscopic lateral trans
      abdominal adrenalectomy for a voluminous AOC (120*95*110 mm) and we review the
      literature regarding AOCs. Laparoscopy in experienced hands is safe and effective
      for the treatment of AONs. Despite the rarity of AOC, a case series should be
      performed to confirm the results of our case report.

PMID- 30217969
TI  - Comparison of Thrombelastography (TEG) in Patients with Acute Cerebral Hemorrhage
      and Cerebral Infarction.
AB  - BACKGROUND The aim of this study was to analyze the changing role of
      thrombelastography (TEG) by detecting the indexes of TEG in patients with acute
      cerebral hemorrhage and cerebral infarction, combined with pathogenesis, and to
      find objective laboratory indexes for the diagnosis and treatment of
      cerebrovascular diseases. MATERIAL AND METHODS Data from 150 patients were
      collected, including 69 cases identified as the cerebral infarction group and 81
      cases identified as the cerebral hemorrhage group. In addition, 50 healthy adults
      were selected as a control group. The cerebral hemorrhage group was divided into
      3 subgroups according to the amount of bleeding: small hemorrhage group, moderate
      hemorrhage group, and large hemorrhage group. The diagnosis for each participant
      was mainly based on computed tomography (CT) and magnetic resonance imaging
      (MRI). TEG indexes [R value (coagulation reaction time), K value (coagulation
      time), Angle (reflecting the formation rate of blood clot and the function of
      fibrinogen), MA (maximum thrombus amplitude), CI (coagulation index)] were
      measured by TEG YZ5000 instrument. RESULTS The cerebral infarction group had
      lower R and K values and higher Angle and CI (P<0.05). The cerebral hemorrhage
      group had higher K value; the Angle and MA were lower in the moderate hemorrhage
      group and in the large hemorrhage groups (P<0.05). In the cerebral hemorrhage
      group, Angle and MA were negatively correlated with the amount of cerebral
      hemorrhage (r=-0.475, -0.394 respectively, P<0.05), and the K value was
      positively correlated with the amount of cerebral hemorrhage (r=0.337, P<0.05),
      while the R value had no significant correlation with the amount of cerebral
      hemorrhage (r=0.251, P>0.05). R and K values in the cerebral infarction group
      were significantly lower, while Angle, MA, and CI were significantly higher in
      the cerebral hemorrhage group. CONCLUSIONS K value, Angle, and MA may be of value
      in the assessment of the amount of cerebral hemorrhage.

PMID- 30217970
TI  - rec-YnH enables simultaneous many-by-many detection of direct protein-protein and
      protein-RNA interactions.
AB  - Knowing which proteins and RNAs directly interact is essential for understanding
      cellular mechanisms. Unfortunately, discovering such interactions is costly and
      often unreliable. To overcome these limitations, we developed rec-YnH, a new
      yeast two and three-hybrid-based screening pipeline capable of detecting
      interactions within protein libraries or between protein libraries and RNA
      fragment pools. rec-YnH combines batch cloning and transformation with
      intracellular homologous recombination to generate bait-prey fusion libraries. By
      developing interaction selection in liquid-gels and using an ORF sequence-based
      readout of interactions via next-generation sequencing, we eliminate laborious
      plating and barcoding steps required by existing methods. We use rec-Y2H to
      simultaneously map interactions of protein domains and reveal novel putative
      interactors of PAR proteins. We further employ rec-Y2H to predict the
      architecture of published coprecipitated complexes. Finally, we use rec-Y3H to
      map interactions between multiple RNA-binding proteins and RNAs-the first time
      interactions between protein and RNA pools are simultaneously detected.

PMID- 30217971
TI  - Genome-wide association study of seasonal affective disorder.
AB  - Family and twin studies have shown a genetic component to seasonal affective
      disorder (SAD). A number of candidate gene studies have examined the role of
      variations within biologically relevant genes in SAD susceptibility, but few
      genome-wide association studies (GWAS) have been performed to date. The authors
      aimed to identify genetic risk variants for SAD through GWAS. The authors
      performed a GWAS for SAD in 1380 cases and 2937 controls of European-American
      (EA) origin, selected from samples for GWAS of major depressive disorder and of
      bipolar disorder. Further bioinformatic analyses were conducted to examine
      additional genomic and biological evidence associated with the top GWAS signals.
      No susceptibility loci for SAD were identified at a genome-wide significant
      level. The strongest association was at an intronic variant (rs139459337) within
      ZBTB20 (odds ratio (OR) = 1.63, p = 8.4 * 10-7), which encodes a transcriptional
      repressor that has roles in neurogenesis and in adult brain. Expression
      quantitative trait loci (eQTL) analysis showed that the risk allele "T" of
      rs139459337 is associated with reduced mRNA expression of ZBTB20 in human
      temporal cortex (p = 0.028). Zbtb20 is required for normal murine circadian
      rhythm and for entrainment to a shortened day. Of the 330 human orthologs of
      murine genes directly repressed by Zbtb20, there were 32 associated with SAD in
      our sample (at p < 0.05), representing a significant enrichment of ZBTB20 targets
      among our SAD genetic association signals (fold = 1.93, p = 0.001). ZBTB20 is a
      candidate susceptibility gene for SAD, based on a convergence of genetic,
      genomic, and biological evidence. Further studies are necessary to confirm its
      role in SAD.

PMID- 30217972
TI  - A conserved glycine harboring disease-associated mutations permits NMDA receptor
      slow deactivation and high Ca2+ permeability.
AB  - A variety of de novo and inherited missense mutations associated with
      neurological disorders are found in the NMDA receptor M4 transmembrane helices,
      which are peripheral to the pore domain in eukaryotic ionotropic glutamate
      receptors. Subsets of these mutations affect receptor gating with dramatic
      effects, including in one instance halting it, occurring at a conserved glycine
      near the extracellular end of M4. Functional experiments and molecular dynamic
      simulations of constructs with and without substitutions at this glycine indicate
      that it acts as a hinge, permitting the intracellular portion of the ion channel
      to laterally expand. This expansion stabilizes long-lived open states leading to
      slow deactivation and high Ca2+ permeability. Our studies provide a functional
      and structural framework for the effect of missense mutations on NMDARs at
      central synapses and highlight how the M4 segment may represent a pathway for
      intracellular modulation of NMDA receptor function.

PMID- 30217973
TI  - HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1
      activation via IKKalpha.
AB  - The selective removal of undesired or damaged mitochondria by autophagy, known as
      mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion,
      neurodegeneration and ageing. The pro-autophagic molecule AMBRA1
      (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of
      mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we
      identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1
      mediated mitophagy, a process that takes place independently of the main
      mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is
      post-translationally controlled, upon HUWE1 activity, by a positive
      phosphorylation on its serine 1014. This modification is mediated by the IKKalpha
      kinase and induces structural changes in AMBRA1, thus promoting its interaction
      with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these
      results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in
      which HUWE1 and IKKalpha are key factors, shedding new lights on the regulation
      of mitochondrial quality control and homoeostasis in mammalian cells.

PMID- 30217974
TI  - Proteomics reveals signal peptide features determining the client specificity in
      human TRAP-dependent ER protein import.
AB  - In mammalian cells, one-third of all polypeptides are transported into or across
      the ER membrane via the Sec61 channel. While the Sec61 complex facilitates
      translocation of all polypeptides with amino-terminal signal peptides (SP) or
      transmembrane helices, the Sec61-auxiliary translocon-associated protein (TRAP)
      complex supports translocation of only a subset of precursors. To characterize
      determinants of TRAP substrate specificity, we here systematically identify TRAP
      dependent precursors by analyzing cellular protein abundance changes upon TRAP
      depletion using quantitative label-free proteomics. The results are validated in
      independent experiments by western blotting, quantitative RT-PCR, and
      complementation analysis. The SPs of TRAP clients exhibit above-average glycine
      plus-proline content and below-average hydrophobicity as distinguishing features.
      Thus, TRAP may act as SP receptor on the ER membrane's cytosolic face,
      recognizing precursor polypeptides with SPs of high glycine-plus-proline content
      and/or low hydrophobicity, and triggering substrate-specific opening of the Sec61
      channel through interactions with the ER-lumenal hinge of Sec61alpha.

PMID- 30217975
TI  - Mapping a hidden terrane boundary in the mantle lithosphere with lamprophyres.
AB  - Lamprophyres represent hydrous alkaline mantle melts that are a unique source of
      information about the composition of continental lithosphere. Throughout
      southwest Britain, post-Variscan lamprophyres are (ultra)potassic with strong
      incompatible element enrichments. Here we show that they form two distinct groups
      in terms of their Sr and Nd isotopic compositions, occurring on either side of a
      postulated, hitherto unrecognized terrane boundary. Lamprophyres emplaced north
      of the boundary fall on the mantle array with epsilonNd -1 to +1.6. Those south
      of the boundary are enriched in radiogenic Sr, have initial epsilonNd values of 
      0.3 to -3.5, and are isotopically indistinguishable from similar-aged
      lamprophyres in Armorican massifs in Europe. We conclude that an Armorican
      terrane was juxtaposed against Avalonia well before the closure of the Variscan
      oceans and the formation of Pangea. The giant Cornubian Tin-Tungsten Ore Province
      and associated batholith can be accounted for by the fertility of Armorican lower
      crust and mantle lithosphere.

PMID- 30217976
TI  - All carbon materials pn diode.
AB  - Semiconductor pn junctions are elementary building blocks of many electronic
      devices such as transistors, solar cells, photodetectors, and integrated
      circuits. Due to the absence of an energy bandgap and massless Dirac-like
      behaviour of charge carriers, graphene pn junction with electrical current
      rectification characteristics is hardly achieved. Here we show a graphene pn
      junction diode can be made exclusively from carbon materials by laminating two
      layers of positively and negatively charged graphene oxides. As the
      interdiffusion of oppositely charged mobile counterions, a built-in potential is
      created to rectify the current by changing the tunnelling probability of
      electrons across the junction. This graphene diode is semi-transparent, can
      perform simple logic operations, and since it has carbon nanotubes electrodes, we
      demonstrate an all carbon materials pn diode. We expect this graphene diode will
      expand material choices and provide functionalities (e.g. grafting recognition
      units on graphene oxides) beyond that of traditional semiconductor pn junctions.

PMID- 30217977
TI  - Nanomaterials design for super-degenerate electronic state beyond the limit of
      geometrical symmetry.
AB  - Spherical atoms have the highest geometrical symmetry. Due to this symmetry,
      atomic orbitals are highly degenerate, leading to closed-shell stability and
      magnetism. No substances with greater degrees of degeneracy are known, due to
      geometrical limitations. We now propose that realistic magnesium, zinc, and
      cadmium clusters having a specific tetrahedral framework possess anomalous higher
      fold degeneracies than spherical symmetry. Combining density functional theory
      calculations with simple tight-binding models, we demonstrate that these
      degeneracies can be attributed to dynamical symmetry. The degeneracy condition is
      fully identified as an elegant mathematical sequence involving interatomic
      parameters. The introduction of dynamical symmetry will lead to the discovery of
      a novel category of substances with super-degenerate orbitals.

PMID- 30217978
TI  - The ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone
      acetylation and gene activation.
AB  - Recognition of histones by epigenetic readers is a fundamental mechanism for the
      regulation of chromatin and transcription. Most reader modules target specific
      post-translational modifications on histones. Here, we report the identification
      of a reader of histone H3, the ZZ-type zinc finger (ZZ) domain of ZZZ3, a subunit
      of the Ada-two-A-containing (ATAC) histone acetyltransferase complex. The
      solution NMR structure of the ZZ in complex with the H3 peptide reveals a unique
      binding mechanism involving caging of the N-terminal Alanine 1 of histone H3 in
      an acidic cavity of the ZZ domain, indicating a specific recognition of H3 versus
      other histones. Depletion of ZZZ3 or disruption of the ZZ-H3 interaction dampens
      ATAC-dependent promoter histone H3K9 acetylation and target gene expression.
      Overall, our study identifies the ZZ domain of ZZZ3 as a histone H3 reader that
      is required for the ATAC complex-mediated maintenance of histone acetylation and
      gene activation.

PMID- 30217979
TI  - Structural determinants of Rab11 activation by the guanine nucleotide exchange
      factor SH3BP5.
AB  - The GTPase Rab11 plays key roles in receptor recycling, oogenesis, autophagosome
      formation, and ciliogenesis. However, investigating Rab11 regulation has been
      hindered by limited molecular detail describing activation by cognate guanine
      nucleotide exchange factors (GEFs). Here, we present the structure of Rab11 bound
      to the GEF SH3BP5, along with detailed characterization of Rab-GEF specificity.
      The structure of SH3BP5 shows a coiled-coil architecture that mediates exchange
      through a unique Rab-GEF interaction. Furthermore, it reveals a rearrangement of
      the switch I region of Rab11 compared with solved Rab-GEF structures, with a
      constrained conformation when bound to SH3BP5. Mutation of switch I provides
      insights into the molecular determinants that allow for Rab11 selectivity over
      evolutionarily similar Rab GTPases present on Rab11-positive organelles.
      Moreover, we show that GEF-deficient mutants of SH3BP5 show greatly decreased
      Rab11 activation in cellular assays of active Rab11. Overall, our results give
      molecular insight into Rab11 regulation, and how Rab-GEF specificity is achieved.

PMID- 30217980
TI  - Abrupt drainage basin reorganization following a Pleistocene river capture.
AB  - River capture is a dramatic natural process of internal competition through which
      mountainous landscapes evolve and respond to perturbations in tectonics and
      climate. River capture may occur when one river network grows at the expense of
      another, resulting in a victor that steals the neighboring headwaters. While
      river capture occurs regularly in numerical models, field observations are rare.
      Here we document a late Pleistocene river capture in the Yimeng Mountains, China
      that abruptly shifted 25 km2 of drainage area from one catchment to another.
      River terraces and imbricated cobbles indicate that the main channel incised 27 m
      into granitic bedrock within 80 kyr, following the capture event, and upstream
      propagating knickpoints and waterfalls reversed the flow direction of a major
      river. Topographic analysis shows that the capture shifted the river basins far
      from topographic equilibrium, and active divide migration is propagating the
      effects of the capture throughout the landscape.

PMID- 30217981
TI  - Aerosol-induced intensification of cooling effect of clouds during Indian summer
      monsoon.
AB  - Measurements and models show that enhanced aerosol concentrations can modify
      macro- and micro-physical properties of clouds. Here, we examine the effect of
      aerosols on continental mesoscale convective cloud systems during the Indian
      summer monsoon and find that these aerosol-cloud interactions have a net cooling
      effect at the surface and the top-of-atmosphere. Long-term (2002-2016) satellite
      data provide evidence of aerosol-induced cloud invigoration effect (AIvE) during
      the Indian summer monsoon. The AIvE leads to enhanced formation of thicker
      stratiform anvil clouds at higher altitudes. These AIvE-induced stratiform anvil
      clouds are also relatively brighter because of the presence of smaller sized ice
      particles. As a result, AIvE-induced increase in shortwave cloud radiative
      forcing is much larger than longwave cloud radiative forcing leading to the
      intensified net cooling effect of clouds over the Indian summer monsoon region.
      Such aerosol-induced cooling could subsequently decrease the surface diurnal
      temperature range and have significant feedbacks on lower tropospheric turbulence
      in a warmer and polluted future scenario.

PMID- 30217982
TI  - Parsing cultural impacts on regret and risk in Iran, China and the United
      Kingdom.
AB  - Value-based choices are influenced both by powerful counterfactuals, such as
      regret, and also by risk in potential outcomes. Culture can profoundly affect how
      humans perceive and act in the world, but it remains unknown how regret in value
      based choice and key aspects of risk-taking may differ between cultures. Here our
      computational approach provides precise and independent metrics, grounded in
      extensive neurobiological evidence, for the influences of risk and regret on
      choice. We test for commonalities and differences across three diverse cultures:
      Iran, China and the UK. Including Iran matters because cross-cultural work on
      value-based choice is lacking for this key 21st Century culture, and also because
      patterns across the three cultures arbitrates between explanations for
      differences. We find commonalities, with regret influencing choice across
      cultures and no consistent cultural difference seen. However, for risk, unlike in
      both Chinese and Westerners' choices, Iranians are risk-seeking - findings
      consistent across two task variants and further explained by Iranians showing
      less subjective impact of negative, but not positive, outcomes of risky choices.
      Our computational approach dissects cultural impacts on two key neurobiologically
      grounded quantities in value-based choice, showing that neuroscientific accounts
      cannot a priori isolate such quantities from culture in the cognitive processes
      underlying choice.

PMID- 30217983
TI  - Contributions of biogenic material to the atmospheric ice-nucleating particle
      population in North Western Europe.
AB  - A minute fraction of atmospheric particles exert a disproportionate effect on the
      phase of mixed-phase clouds by acting as ice-nucleating particles (INPs). To
      understand the effects of these particles on weather and climate, both now and
      into the future, we must first develop a quantitative understanding of the major
      INP sources worldwide. Previous work has demonstrated that aerosols such as
      desert dusts are globally important INPs, but the role of biogenic INPs is
      unclear, with conflicting evidence for their importance. Here, we show that at a
      temperate site all INPs active above -18  degrees C at concentrations >0.1 L-1
      are destroyed on heating, consistent with these INPs being of biological origin.
      Furthermore, we show that a global model of desert dust INPs dramatically
      underestimates the measured INP concentrations, but is consistent with the
      thermally-stable component. Notably, the heat sensitive INPs are active at
      temperatures where shallow cloud layers in Northern Europe are frequently
      observed to glaciate. Hence, we suggest that biogenic material is important for
      primary ice production in this region. The prevalence of heat sensitive, most
      likely biogenic, INPs in this region highlights that, as a community, we need to
      quantify the sources and transport of these particles as well as determine their
      atmospheric abundance across the globe and at cloud altitudes.

PMID- 30217984
TI  - Genetic diversity and phylogeny of South African Meloidogyne populations using
      genotyping by sequencing.
AB  - Meloidogyne species cause great crop losses worldwide. Although genetic host
      plant resistance is an effective control strategy to minimize damage caused by
      Meloidogyne, some resistant genes are ineffective against virulent species such
      as Meloidogyne enterolobii. Detailed knowledge about the genetic composition of
      Meloidogyne species is thus essential. This study focused on genotyping-by
      sequencing (GBS) and Pool-Seq to elucidate the genetic relation between South
      African M. enterolobii, M. incognita and M. javanica populations. Hence, 653
      common single nucleotide polymorphisms (SNPs) were identified and used to compare
      these species at genetic level. Allele frequencies of 34 SNPs consistently
      differed between the three Meloidogyne species studied. Principal component and
      phylogenetic analyses grouped the M. enterolobii populations in one clade,
      showing a distant relation to the M. javanica populations. These two species also
      shared genetic links with the M. incognita populations studied. GBS has been used
      successfully in this study to identify SNPs that discriminated among the three
      Meloidogyne species investigated. Alleles, only occurring in the genome of M.
      enterolobii and located in genes involved in virulence in other animal species
      (e.g. a serine/threonine phosphatase and zinc finger) have also been identified,
      accentuating the value of GBS in future studies of this nature.

PMID- 30217985
TI  - Selective reduction and homologation of carbon monoxide by organometallic iron
      complexes.
AB  - Carbon monoxide is a key C1 feedstock for the industrial production of
      hydrocarbons, where it is used to make millions of tonnes of chemicals, fuels,
      and solvents per annum. Many transition metal complexes can coordinate CO, but
      the formation of new C-C bonds in well-defined compounds from the scission and
      subsequent coupling of two or more CO moieties at a transition metal centre
      remains a challenge. Herein, we report the use of low-coordinate iron(II)
      complexes for the selective scission and homologation of CO affording unusual
      squaraines and iron carboxylates at ambient temperature and pressure. A
      modification of the ligand framework allows for the isolation and structural
      characterisation of a proposed metallacyclic Fe(II) carbene intermediate. These
      results indicate that, with the appropriate choice of supporting ligands, it is
      possible to cleave and homologate carbon monoxide under mild conditions using an
      abundant and environmentally benign low-coordinate, first row transition metal.

PMID- 30217986
TI  - AAV serotype 8-mediated liver specific GNMT expression delays progression of
      hepatocellular carcinoma and prevents carbon tetrachloride-induced liver damage.
AB  - Glycine N-methyltransferase (GNMT) is abundantly expressed in normal livers and
      plays a protective role against tumor formation. GNMT depletion leads to
      progression of hepatocellular carcinoma (HCC). In this study, we investigated the
      activity of ectopic GNMT delivered using recombinant adeno-associated virus (AAV)
      gene therapy in mouse models of liver cirrhosis and HCC. Injection of AAV
      serotype 8 (AAV8) vector carrying the GNMT gene (AAV8-GNMT) in Gnmt-/- mice
      increased GNMT expression and downregulated pro-inflammatory responses, resulting
      in reduced liver damage and incidence of liver tumors. Moreover, AAV8-GNMT
      resulted in the amelioration of carbon tetrachloride (CCl4)-induced liver
      fibrosis in BALB/c mice. We showed that AAV8-GNMT protected hepatocytes from CCl4
      induced liver damage.  AAV8-GNMT significantly attenuated the levels of pro
      fibrotic markers and increased efficiency of hepatocyte proliferation. These
      results suggest that correction of hepatic GNMT by gene therapy of AAV8-mediated
      gene enhancement may provide a potential strategy for preventing and delaying
      development of liver diseases.

PMID- 30217987
TI  - Tidal and hydrological periodicities of seismicity reveal new risk scenarios at
      Campi Flegrei caldera.
AB  - The volcano-tectonic seismicity occurring at Campi Flegrei caldera during its
      present unrest phase, started in 2005, is distributed into time-clustered events
      emerging from a background composed of earthquakes with higher inter-arrival
      times. Here, we show that clustered seismicity is cyclically recurrent at time
      scales from semidiurnal to annual, matching tidal and hydrological periodicities.
      These results suggest that volcano-tectonic seismicity at Campi Flegrei caldera
      is driven by both variations in the deep magmatic feeding system and exogenous
      phenomena, as rainfall or global inflation/deflation cycles of the Earth's crust,
      controlled by the lunisolar interaction. Consequently, the role of exogenous
      triggers in the evolution of the present unrest phase should be properly
      considered in the elaboration of volcanic risk scenarios, presently limited to
      the study of surface indicators of deep phenomena.

PMID- 30217988
TI  - Untargeted analysis of the airway proteomes of children with respiratory
      infections using mass spectrometry based proteomics.
AB  - The upper airway - which consists mainly of the naso- and oro-pharynx - is the
      first point of contact between the respiratory system and microbial organisms
      that are ubiquitous in the environment. It has evolved highly specialised
      functions to address these constant threats whilst facilitating seamless
      respiratory exchange with the lower respiratory tract. Dysregulation of its
      critical homeostatic and defence functions can lead to ingress of pathogens into
      the lower respiratory tract, potentially leading to serious illness. Systems-wide
      proteomic tools may facilitate a better understanding of mechanisms in the upper
      airways in health and disease. In this study, we aimed to develop a mass
      spectrometry based proteomics method for characterizing the upper airways
      proteome. Naso- and oropharyngeal swab samples used in all our experiments had
      been eluted in the Universal Transport Media (UTM) containing significantly high
      levels of bovine serum albumin. Our proteomic experiments tested the optimal
      approach to characterize airway proteome on swab samples eluted in UTM based on
      the number of proteins identified without BSA depletion (Total proteome: Protocol
      A) and with its depletion using a commercial kit; Allprep, Qiagen (cellular
      proteome: Protocol B, Ci, and Cii). Observations and lessons drawn from protocol
      A, fed into the design and implementation of protocol B, and from B to protocol
      Ci and finally Cii. Label free proteome quantification was used in Protocol A (n
      = 6) and B (n = 4) while commercial TMT 10plex reagents were used for protocols
      Ci and ii (n = 83). Protocols Ci and ii were carried out under similar conditions
      except for the elution gradient: 3 h and 6 h respectively. Swab samples tested in
      this study were from infants and children with and without upper respiratory
      tract infections from Kilifi County Hospital on the Kenyan Coast. Protocol A had
      the least number of proteins identified (215) while B produced the highest number
      of protein identifications (2396). When Protocol B was modified through sample
      multiplexing with TMT to enable higher throughput (Protocol Ci), the number of
      protein identified reduced to 1432. Modification of protocol Ci by increasing the
      peptide elution time generated Protocol Cii that substantially increased the
      number of proteins identified to 1875. The coefficient of variation among the TMT
      runs in Protocol Cii was <20%. There was substantial overlap in the identity of
      proteins using the four protocols. Our method was were able to identify marker
      proteins characteristically expressed in the upper airway. We found high
      expression levels of signature nasopharyngeal and oral proteins, including
      BPIFA1/2 and AMY1A, as well as a high abundance of proteins related to innate and
      adaptive immune function in the upper airway. We have developed a sensitive
      systems-level proteomic assay for the systematic quantification of naso-oro
      pharyngeal proteins. The assay will advance mechanistic studies of respiratory
      pathology, by providing an untargeted and hypothesis-free approach of examining
      the airway proteome.

PMID- 30217989
TI  - Direct measurement of the capillary condensation time of a water nanobridge.
AB  - Water menisci wet all sorts of cavities, produce among the most intense forces at
      the nanoscale and play a role in many physical and chemical processes. The
      physical properties of these menisci are therefore relevant to understand a
      multitude of phenomena at the nanoscale where these are involved. Here, using a
      force feedback microscope, we directly measured the capillary condensation time
      of a water meniscus, by approaching two surfaces at different speeds and
      monitoring the relative position of the surfaces at the instant the meniscus is
      formed.

PMID- 30217990
TI  - The mechanical principles behind the golden ratio distribution of veins in plant
      leaves.
AB  - Tree leaves are commonly composed of thin mesophyll, carrying out photosynthesis
      under sunlight, and thick veins. Although the role of leaf veins in water
      transportation has been known for a long time, their role in providing structural
      support and guaranteeing large sunlighted area was rarely studied and remains
      elusive. Here, with use of a novel inverse optimization approach, we aim for
      uncovering the material design principle behind the unique pattern of venation.
      It is intriguing to observe that an almost Golden Ratio (GR) distribution of leaf
      veins always provides optimized structural behavior. Specifically, our research
      reveals, for the first time, that this unique GR distribution of relatively
      strong vein material is helpful for maximizing the bending stiffness and leading
      to a large sunlighted area which is vital for the photosynthesis process of a
      leaf. Moreover, the GR distribution of leaf veins is also observed in a wide
      class of plant leaf geometries (i.e., shape, thickness), where experimental
      evidence is provided for the optimized results. Therefore, our findings can not
      only serve to explain the mystery of veins GR distribution but also provide
      widely applicable guidelines on designing soft structures with exceptional
      mechanical performances.

PMID- 30217991
TI  - Modular DNA strand-displacement controllers for directing material expansion.
AB  - Soft materials that swell or change shape in response to external stimuli show
      extensive promise in regenerative medicine, targeted therapeutics, and soft
      robotics. Generally, a stimulus for shape change must interact directly with the
      material, limiting the types of stimuli that may be used and necessitating high
      stimulus concentrations. Here, we show how DNA strand-displacement controllers
      within hydrogels can mediate size change by interpreting, amplifying, and
      integrating stimuli and releasing signals that direct the response. These
      controllers tune the time scale and degree of DNA-crosslinked hydrogel swelling
      and can actuate dramatic material size change in response to <100 nM of a
      specific biomolecular input. Controllers can also direct swelling in response to
      small molecules or perform logic. The integration of these stimuli-responsive
      materials with biomolecular circuits is a major step towards autonomous soft
      robotic systems in which sensing and actuation are implemented by biomolecular
      reaction networks.

PMID- 30217992
TI  - Predicting proteome dynamics using gene expression data.
AB  - While protein concentrations are physiologically most relevant, measuring them
      globally is challenging. mRNA levels are easier to measure genome-wide and hence
      are typically used to infer the corresponding protein abundances. The steady
      state condition (assumption that protein levels remain constant) has typically
      been used to calculate protein concentrations, as it is mathematically
      convenient, even though it is often not satisfied. Here, we propose a method to
      estimate genome-wide protein abundances without this assumption. Instead, we
      assume that the system returns to its baseline at the end of the experiment,
      which is true for cyclic phenomena (e.g. cell cycle) and many time-course
      experiments. Our approach only requires availability of gene expression and
      protein half-life data. As proof-of-concept, we predicted proteome dynamics
      associated with the budding yeast cell cycle, the results are available for
      browsing online at http://dynprot.cent.uw.edu.pl/ . The approach was validated
      experimentally by verifying that the predicted protein concentration changes were
      consistent with measurements for all proteins tested. Additionally, if proteomic
      data are available as well, we can also infer changes in protein half-lives in
      response to posttranslational regulation, as we did for Clb2, a post
      translationally regulated protein. The predicted changes in Clb2 abundance are
      consistent with earlier observations.

PMID- 30217993
TI  - Differences in the intrinsic chondrogenic potential of equine umbilical cord
      matrix and cord blood mesenchymal stromal/stem cells for cartilage regeneration.
AB  - Umbilical cord blood mesenchymal stromal/stem cells (UCB-MSCs) and umbilical cord
      matrix MSCs (UCM-MSCs) have chondrogenic potential and are alternative sources to
      standard surgically derived bone marrow or adipose tissue collection for
      cartilage engineering. However, the majority of comparative studies explore
      neonatal MSCs potential only on ISCT benchmark assays accounting for some bias in
      the reproducibility between in vitro and in clinical studies. Therefore, we
      characterized equine UCB-MSCs and UCM-MSCs and investigated with particular
      attention their chondrogenesis potential in 3D culture with BMP-2 + TGF-beta1 in
      normoxia or hypoxia. We carried out an exhaustive characterization of the
      extracellular matrix generated by both these two types of MSCs after the
      induction of chondrogenesis through evaluation of hyaline cartilage, hypertrophic
      and osteogenic markers (mRNA, protein and histology levels). Some differences in
      hypoxia sensitivity and chondrogenesis were observed. UCB-MSCs differentiated
      into chondrocytes express an abundant, dense and a hyaline-like cartilage matrix.
      By contrast, despite their expression of cartilage markers, UCM-MSCs failed to
      express a relevant cartilage matrix after chondrogenic induction. Both MSCs types
      also displayed intrinsic differences at their undifferentiated basal status, UCB
      MSCs expressing higher levels of chondrogenic markers whereas UCM-MSCs
      synthesizing higher amounts of osteogenic markers. Our results suggest that UCB
      MSCs should be preferred for ex-vivo horse cartilage engineering. How those
      results should be translated to in vivo direct cartilage regeneration remains to
      be determined through dedicated study.

PMID- 30217994
TI  - Metabolomic Profile Predicts Development of Microalbuminuria in Individuals with
      Type 1 Diabetes.
AB  - Elevated urinary albumin excretion (microalbuminuria) is an early marker of
      diabetic nephropathy, but there is an unmet need for better biomarkers that
      capture the individuals at risk with higher accuracy and earlier than the current
      markers do. We performed an untargeted metabolomic study to assess baseline
      differences between individuals with type 1 diabetes who either developed
      microalbuminuria or remained normoalbuminuric. A total of 102 individuals
      progressed to microalbuminuria during a median follow-up of 3.2 years, whereas 98
      sex-, age- and body mass index (BMI) matched non-progressors remained
      normoalbuminuric during a median follow-up of 7.1 years. Metabolomic screening
      identified 1,242 metabolites, out of which 111 differed significantly between
      progressors and non-progressors after adjustment for age of diabetes onset,
      baseline glycosylated hemoglobin A1c (HbA1c), and albumin excretion rate (AER).
      The metabolites that predicted development of microalbumiuria included several
      uremic toxins and carnitine metabolism related molecules. Iterative variable
      selection indicated erythritol, 3-phenylpropionate, and N-trimethyl-5
      aminovalerate as the best set of variables to predict development of
      microalbuminuria. A metabolomic index based on these metabolites improved the
      prediction of incident microalbuminuria on top of the clinical variables age of
      diabetes onset, baseline HbA1c and AER (ROCAUC = 0.842 vs 0.797), highlighting
      their ability to predict early-phase diabetic nephropathy.

PMID- 30217995
TI  - Within-colony genetic diversity differentially affects foraging, nest
      maintenance, and aggression in two species of harvester ants.
AB  - There is accumulating evidence that genetic diversity improves the behavioral
      performance and consequently the fitness in groups of social animals. We examined
      the behavioral performance of colonies of two co-occurring, congeneric harvester
      ant species (Messor arenarius and a non-described Messor sp.) in fitness-related
      behaviors, pertaining to foraging performance, nest maintenance, and aggression.
      We linked these behaviors to the colonial genetic diversity, by genotyping
      workers, using six and five microsatellite markers for M. arenarius and M. sp.,
      respectively. Correlations of genetic diversity with colony performance and
      aggression level contrasted between the two species. In M. arenarius, genetic
      diversity was correlated with foraging performance and nest maintenance but not
      with the overall aggression level, while in M. sp., genetic diversity was
      correlated with the overall aggression level, but not with foraging performance
      or nest maintenance. The two species exhibited similar specific aggression
      levels, with higher aggression shown towards heterospecifics and lower towards
      non-nestmate conspecifics and nestmates. However, M. sp. workers displayed a
      tendency to interact for longer with heterospecifics than did M. arenarius. We
      speculate that the different foraging strategies, group vs. individual foraging,
      and possibly also the different mating systems, contribute to the differences
      found in behavior between the two species.

PMID- 30217997
TI  - MiR-199a-5p regulates sirtuin1 and PI3K in the rat hippocampus with intrauterine
      growth restriction.
AB  - In humans, malnutrition during pregnancy results in intrauterine growth
      restriction (IUGR) and an increased risk of neurological morbidities; altered
      miRNA characteristics have been suggested to contribute to IUGR neurological
      pathogenesis. A miRNA microarray was used to identify differentially expressed
      miRNA molecules in the hippocampi of rats with IUGR. Five of the molecules in
      question were selectively validated using real-time PCR in rats with IUGR. We
      then investigated the role of miR-199a-5p in hippocampal pathology.
      Bioinformatics analysis results suggested that TNF-alpha, caspase-3 and SIRT1
      were potential targets of miR-199a-5p. Changes in PI3K, SIRT1 and caspase-3
      protein expressions levels in the hippocampus were confirmed by Western blot
      analysis (all P < 0.05). Studies using the pheochromocytoma cell line PC12 cells
      and primary neurons demonstrated that miR-199a-5p modulated PI3K, caspase-3 and
      SIRT1 expression. Additionally, there was an inverse correlation between miR-199a
      5p and caspase-3 expression, though dual-luciferase reporter assays showed that
      caspase-3 is not a target of miR-199a-5p. We conclude that IUGR affects
      hippocampal miRNAs characteristics. Our results also indicated that aberrantly
      high expression levels of miR-199a-5p may play an important role in the
      pathogenesis of IUGR by regulating SIRT1 and PI3K.

PMID- 30217996
TI  - Pas Kinase Deficiency Triggers Antioxidant Mechanisms in the Liver.
AB  - Metabolic dysfunction in the liver is the cause of numerous pathologies, which
      are associated with an altered redox state. PASK (PAS Domain Kinase) is a
      nutrient and bioenergetic sensor. We contend that PASK could act as an oxidative
      stress sensor in liver and/or control the metabolic balance, playing a role in
      the mitochondrial homeostasis. Using PASK-deficient mice, we observed that PASK
      deficiency promotes antioxidant response mechanisms: a lower production of
      ROS/RNS under non-fasting conditions, overexpression of genes coding to ROS
      detoxifying enzymes and mitochondrial fusion proteins (MnSod Gpx, Mfn1 and Opa1),
      coactivator Ppargc1a, transcription factors (Pparg and FoxO3a) and deacetylase
      Sirt1. Also, under fasting conditions, PASK deficiency induced the overexpression
      of Ppargc1a, Ppara, Pparg, FoxO3a and Nrf2 leading to the overexpression of genes
      coding to antioxidant enzymes such as MnSOD, Cu/ZnSOD, GPx, HO1 and GCLm.
      Additionally, inducing PINK1 involved in cell survival and mitophagy. These
      changes kept ROS steady levels and improved the regenerative state. We suggest a
      new role for PASK as a controller of oxidative stress and mitochondrial dynamics
      in the liver. In fact, antioxidant response is PASK dependent. PASK-targeting
      could therefore be a good way of reducing the oxidative stress in order to
      prevent or treat liver diseases.

PMID- 30217998
TI  - The gastric mucosal-associated microbiome in patients with gastric polyposis.
AB  - The characteristics of the gastric microbiota in patients with gastric polyposis
      (GP) remain unclear. Given this we collected gastric antrum and gastric body
      biopsies from healthy controls (HC.A and HC.B group) and gastric antrum, gastric
      body and polyp biopsies from patients with multiple gastric polyps (GP.A, GP.B
      and GP.P group) for 16S rDNA sequencing. The results showed that the diversity of
      the gastric flora in the GP group was significantly lower than that of the HC
      group. The gastric flora composition of the GP group was significantly different
      from the HC group. However, flora diversity and compositions in different parts
      of the stomach (gastric antrum, gastric body or polyp tissue) were not
      significantly different. H. pylori abundance could influence the composition of
      gastric microbiota. Meanwhile, patients with fundic gland polyps (FGPs) and those
      with hyperplastic polyps (HPs) had considerably similar gastric bacterial
      compositions. We constructed a microbial dysbiosis index (MDI) based on the
      gastric microbiota at the genus level as a predictive model, and it was able to
      distinguish between individuals in the GP and HC groups. These findings showed
      that intragastric flora dysbiosis may be closely related to the occurrence and
      development of gastric polyps.

PMID- 30217999
TI  - Elevated basal luteinizing hormone does not impair the outcome of human
      menopausal gonadotropin and medroxyprogesterone acetate treatment cycles.
AB  - The potential effects of high basal luteinizing hormone (LH) levels on human
      reproduction were controversial. To demonstrate the effects of elevated basal LH
      levels on the outcome of patients undergoing in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles, we performed a
      retrospective data analysis of 1011 polycystic ovarian syndrome (PCOS) patients
      treated with human menopausal gonadotropin and medroxyprogesterone acetate (hMG +
      MPA) protocol at our center between Nov. 2013 and Jun. 2017. PCOS patients with
      elevated basal LH levels had significantly higher LH exposure during the
      stimulation period. The group with LH >= 10 mIU/mL showed a lower mean total hMG
      dose used but higher numbers of oocytes retrieved, metaphase II oocytes, embryos
      and top-quality embryos developed than the groups with lower basal LH levels.
      Moreover, partial correlation analysis showed that the basal LH level was
      negatively correlated with the total hMG dose but positively correlated with the
      numbers of oocytes retrieved, metaphase II oocytes, embryos, and top-quality
      embryos. There were no significant differences in the rates of oocyte retrieval,
      fertilization, implantation, clinical pregnancy and miscarriage between the
      groups based on frozen embryo transfer (FET). We concluded that elevated basal LH
      level does not impair the final outcome of hMG + MPA-treated IVF/ICSI cycles in
      PCOS women.

PMID- 30218000
TI  - How Behavior of Nontarget Species Affects Perceived Accuracy of Scat Detection
      Dog Surveys.
AB  - Detection dogs, specially trained domestic dogs (Canis familiaris), have become a
      valuable, noninvasive, conservation tool because they remove the dependence of
      attracting species to a particular location. Further, detection dogs locate
      samples independent of appearance, composition, or visibility allowing
      researchers to collect large sets of unbiased samples that can be used in complex
      ecological queries. One question not fully addressed is why samples from
      nontarget species are inadvertently collected during detection dog surveys. While
      a common explanation has been incomplete handler or dog training, our study aimed
      to explore alternative explanations. Our trials demonstrate that a scat's genetic
      profile can be altered by interactions of nontarget species with target scat via
      urine-marking, coprophagy, and moving scats with their mouths, all pathways to
      contamination by nontarget species' DNA. Because detection dogs are trained to
      locate odor independent of masking, the collection of samples with a mixed
      olfactory profile (target and nontarget) is possible. These scats will likely
      have characteristics of target species' scats and are therefore only discovered
      faulty once genetic results indicate a nontarget species. While the collection of
      nontarget scats will not impact research conclusions so long as samples are DNA
      tested, we suggest ways to minimize their collection and associated costs.

PMID- 30218001
TI  - Evaluation of two-point Dixon water-fat separation for liver specific contrast
      enhanced assessment of liver maximum capacity.
AB  - Gadoxetic acid-enhanced magnetic resonance imaging has become a useful tool for
      quantitative evaluation of liver capacity. We report on the importance of
      intrahepatic fat on gadoxetic acid-supported T1 mapping for estimation of liver
      maximum capacity, assessed by the realtime 13C-methacetin breathing test (13C
      MBT). For T1 relaxometry, we used a respective T1-weighted sequence with two
      point Dixon water-fat separation and various flip angles. Both T1 maps of the in
      phase component without fat separation (T1_in) and T1 maps merely based on the
      water component (T1_W) were generated, and respective reduction rates of the T1
      relaxation time (rrT1) were evaluated. A steady considerable decline in rrT1 with
      progressive reduction of liver function could be observed for both T1_in and T1_W
      (p < 0.001). When patients were subdivided into 3 different categories of 13C-MBT
      readouts, the groups could be significantly differentiated by their rrT1_in and
      rrT1_W values (p < 0.005). In a simple correlation model of 13C-MBT values with
      T1_inpost (r = 0.556; p < 0.001), T1_Wpost (r = 0.557; p < 0.001), rrT1_in (r =
      0.711; p < 0.001) and rrT1_W (r = 0.751; p < 0.001), a log-linear correlation has
      been shown. Liver maximum capacity measured with 13C-MBT can be determined more
      precisely from gadoxetic acid-supported T1 mapping when intrahepatic fat is taken
      into account. Here, T1_W maps are shown to be significantly superior to T1_in
      maps without separation of fat.

PMID- 30218002
TI  - A Small Molecule BH3-mimetic Suppresses Cigarette Smoke-Induced Mucous Expression
      in Airway Epithelial Cells.
AB  - Cigarette smoke (CS) exposure is one of the primary risk factors associated with
      the chronic mucous hypersecretion (CMH). The antiapoptotic protein, Bcl-2
      sustains hyperplastic mucous cells, and the airway epithelium of ex-smokers with
      CMH as well as mice exposed to chronic CS showed increased Bcl-2 expression.
      Therefore, we investigated whether Bcl-2 plays a role in CS-induced mucous
      expression. Primary airway epithelial cells (AECs) of murine and human origin
      were treated with CS extract (CSE), and there was a concentration- and time
      dependent increase in secretory mucin (MUC5AC), mucous regulator (SPDEF) and Bcl
      2 expression. Using differentiated human AECs cultured on air-liquid interface,
      EGFR and ERK1/2 pathways were interrogated. Bcl-2 activity was blocked using a
      small molecule BH3 mimetic ABT-263 that disrupts the Bcl-2 interaction with pro
      apoptotic proteins. The ABT-263 treatment resulted in the downregulation of CSE
      induced mucus expression and disrupted the EGFR-signaling while inducing the
      apoptosis and the pro-apoptotic protein, Bik expression. This strategy
      significantly suppressed the mainstream CS-induced mucous phenotype in a 3-D
      human airway epithelium model. Therefore, the present study suggests that CS
      induces Bcl-2 expression to help promote mucous cell survival; and small molecule
      BH3 mimetics targeting Bcl-2 could be useful in suppressing the CS-induced mucous
      response.

PMID- 30218003
TI  - DNA methylation in adolescents with anxiety disorder: a longitudinal study.
AB  - Anxiety disorders (AD) typically manifest in children and adolescents and might
      persist into adulthood. However, there are still few data concerning epigenetic
      mechanisms associated with onset, persistence or remission of AD over time. We
      investigated a cohort of adolescents and young adults at baseline (age; 13.19 +/-
      2.38) and after 5 years and classified them according to the AD diagnosis and
      their longitudinal trajectories into 4 groups: (1) Typically Developing
      Comparisons (TDC; control group, n = 14); (2) Incident (AD in the second
      evaluation only, n = 11); (3) Persistent (AD in both evaluations, n = 14) and (4)
      Remittent (AD in the first evaluation only, n = 8). DNA methylation was evaluated
      with the Infinium HumanMethylation450 BeadChip from saliva samples collected at
      both evaluations. Gene set enrichment analysis was applied to consider biological
      pathways. We found decreased DNA methylation in TDC group while the chronic cases
      of AD presented hypermethylation in central nervous system development pathways.
      Moreover, we showed that this persistent group also presented hypermethylation
      while the other three groups were associated with hypomethylation in nervous
      system development pathway. Incidence and remission groups were associated with
      increased and decreased methylation in neuron development pathways, respectively.
      Larger studies are likely to detect specific genes relevant to AD.

PMID- 30218004
TI  - A new method to improve the prediction of the celestial pole offsets.
AB  - Knowledge of the Earth's changing rotation is fundamental to positioning objects
      in space and on the planet. Nowadays, the Earth's orientation in space is
      expressed by five Earth Orientation Parameters (EOP). Many applications in
      astronomy, geosciences, and space missions require accurate EOP predictions.
      Operational predictions are released daily by the Rapid Service/Prediction Centre
      of the International Earth Rotation and Reference Systems Service (IERS). The
      prediction procedures and performances differ for the three EOP classes: polar
      motion, rotation angle (UT1-UTC), and the two celestial pole offsets (CPO), dX
      and dY. The IERS Annual Report 2016 shows Rapid Service CPO predictions errors
      with respect to IERS 08 C04 observations in 2016 ranging from 120 to 140 MUas in
      40 days for dX, and 100-160 MUas for dY. We test a new method for the CPO
      prediction based on the recent availability of sophisticated empirical models for
      the Free Core Nutation, a main component of the CPO variations. We found it
      allows predicting both CPO with error estimates for the period 2000-2016 lower
      than the 2016 Rapid Service products, reaching about 85 MUas after 40 days and
      near 90 MUas after a year. These results would represent a 35-40% improvement.

PMID- 30218005
TI  - Coupled Resonators for Sound Trapping and Absorption.
AB  - The leakage of sound waves in a resonance based rainbow trapping device prevents
      the sound wave being trapped in a specific location. In this study, we report a
      design of sound trapping device based on coupled Helmholtz resonators, loaded to
      an air waveguide, which can effectively tackle the wave leakage issue. We show
      that coupled resonators structure can generate dips in the transmission spectrum
      by an analytical model derived from Newton's second law and numerical analysis
      based on finite-element method. An effective medium theory is derived, which
      shows that coupled resonators cause a negative effective bulk modulus near the
      resonance frequency and induce flat bands that give rise to the confinement of
      the incoming wave inside the resonators. We compute the transmission spectra and
      band diagram from the effective medium theory, which are consistent with the
      simulation results. Trapping and high absorption of sound wave energy are
      demonstrated with our designed device.

PMID- 30218006
TI  - Diminished gray matter density mediates chemotherapy dosage-related cognitive
      impairment in breast cancer patients.
AB  - To investigate chemotherapy dosage-related cognitive impairment and its neural
      mechanisms in breast cancer (BC) patients. Twenty-eight breast cancer patients
      after each chemotherapy cycle and matched 29 healthy control subjects underwent
      structural magnetic resonance imaging. Voxel-based morphometry analysis was
      performed to compare group differences in the gray matter for the whole brain.
      Furthermore, mediation analysis was conducted to explore the role of brain
      structures in chemotherapy dosage-related cognitive impairment. Voxel-based
      morphometry analysis was performed in gray matter for the whole brain of BC
      patients after chemotherapy. The results revealed that the gray matter density in
      the left inferior frontal gyrus, right middle frontal gyrus, right fusiform area,
      and bilateral cerebellum was decreased in the BC patients compared to controls.
      The number of chemotherapy cycles was negatively associated with general
      cognitive capacity, verbal fluency and digit span performance in the BC patients.
      In addition, decreased gray matter density in the right middle frontal gyrus
      could mediate the chemotherapy dosage effects on verbal fluency performance.
      These findings indicate that the dose-response relationship between chemotherapy
      and cognitive impairment may depend on the decreases in gray matter density of
      the frontal cortical structures.

PMID- 30218007
TI  - Skeletal muscle metabolomics and blood biochemistry analysis reveal metabolic
      changes associated with dietary amino acid supplementation in dairy calves.
AB  - The effects of different amino acid (AA) supplementations of milk protein-based
      milk replacers in pre-ruminant calves from 3 days to 7 weeks of age were studied.
      Animals were divided into 4 groups: Ctrl) Control group fed with milk protein
      based milk replacer without supplementation; GP) supplementation with 0.1%
      glycine and 0.3% proline; FY) supplementation with 0.2% phenylalanine and 0.2%
      tyrosine; MKT) supplementation with 0.62% lysine, 0.22% methionine and 0.61%
      threonine. For statistical analysis, t-test was used to compare AA-supplemented
      animals to the Ctrl group. At week 7, body weight and average daily gain (ADG)
      were measured and blood samples and skeletal muscle biopsies were taken. Blood
      biochemistry analytes related to energy metabolism were determined and it was
      shown that MKT group had higher serum creatinine and higher plasma concentration
      of three supplemented AAs as well as arginine compared with the Ctrl group. GP
      group had similar glycine/proline plasma concentration compared with the other
      groups while in FY group only plasma phenylalanine concentration was higher
      compared with Control. Although the AA supplementations in the GP and FY groups
      did not affect average daily gain and metabolic health profile from serum, the
      metabolome analysis from skeletal muscle biopsy revealed several differences
      between the GP-FY groups and the Ctrl-MKT groups, suggesting a metabolic
      adaptation especially in GP and FY groups.

PMID- 30218008
TI  - Correction: Pomalidomide, bortezomib, and low-dose dexamethasone in lenalidomide
      refractory and proteasome inhibitor-exposed myeloma.
AB  - Following the publication of this article, the authors noted that the
      pomalidomide dose for the additional SC cohort in Fig. 1 was incorrectly listed.
      The correct dose for pomalidomide in the additional SC cohort should be the
      maximum tolerated dose of 4 mg/day, not 2 mg/day as listed in the original Fig.
      1. The authors apologize for any inconvenience caused.

PMID- 30218009
TI  - Correction: NG2 antigen is involved in leukemia invasiveness and central nervous
      system infiltration in MLL-rearranged infant B-ALL.
AB  - The original version of this Article contained an error in the spelling of the
      author Juan Carlos Rodriguez-Manzaneque, which was incorrectly given as J Carlos
      Rodriguez-Manzaneque. This has now been corrected in both the PDF and HTML
      versions of the Article.

PMID- 30218010
TI  - Two Tau binding sites on tubulin revealed by thiol-disulfide exchanges.
AB  - Tau is a Microtubule-associated protein that induces and stabilizes the formation
      of the Microtubule cytoskeleton and plays an important role in neurodegenerative
      diseases. The Microtubules binding region of Tau has been determined for a long
      time but where and how Tau binds to its partner still remain a topic of debate.
      We used Site Directed Spin Labeling combined with EPR spectroscopy to monitor Tau
      upon binding to either Taxol-stabilized MTs or to alphabeta-tubulin when Tau is
      directly used as an inducer of MTs formation. Using maleimide-functionalized
      labels grafted on the two natural cysteine residues of Tau, we found in both
      cases that Tau remains highly flexible in these regions confirming the fuzziness
      of Tau:MTs complexes. More interestingly, using labels linked by a disulfide
      bridge, we evidenced for the first time thiol disulfide exchanges between
      alphabeta-tubulin or MTs and Tau. Additionally, Tau fragments having the two
      natural cysteines or variants containing only one of them were used to determine
      the role of each cysteine individually. The difference observed in the label
      release kinetics between preformed MTs or Tau-induced MTs, associated to a
      comparison of structural data, led us to propose two putative binding sites of
      Tau on alphabeta-tubulin.

PMID- 30218011
TI  - Important contributions of sea-salt aerosols to atmospheric bromine cycle in the
      Antarctic coasts.
AB  - Polar sunrise activates reactive bromine (BrOx) cycle on the Antarctic coasts.
      BrOx chemistry relates to depletion of O3 and Hg in polar regions. Earlier
      studies have indicated "blowing snow" as a source of atmospheric BrOx. However,
      surface O3 depletion and BrO enhancement occurs rarely under blowing snow
      conditions at Syowa Station, Antarctica. Therefore, trigger processes for BrOx
      activation other than the heterogeneous reactions on blowing snow particles must
      be considered. Results of this study show that enhancement of sea-salt aerosols
      (SSA) and heterogeneous reactions on SSA are the main key processes for
      atmospheric BrOx cycle activation. Blowing snow had Br- enrichment, in contrast
      to strong Br- depletion in SSA. In-situ aerosol measurements and satellite BrO
      measurements demonstrated clearly that a BrO plume appeared simultaneously in SSA
      enhancement near the surface. Results show that surface O3 depletion at Syowa
      Station occurred in aerosol enhancement because of SSA dispersion during the
      polar sunrise. Amounts of depleted Br- from SSA were matched well to the
      tropospheric vertical column density of BrO and BrOx concentrations found in
      earlier work. Our results indicate that SSA enhancement by strong winds engenders
      activation of atmospheric BrOx cycles via heterogeneous reactions on SSA.

PMID- 30218012
TI  - Randomized trial examining effectiveness of lifestyle intervention in reducing
      gestational diabetes in high risk Chinese pregnant women in Hong Kong.
AB  - Gestational diabetes mellitus (GDM) is of public health concern. This trial
      examined whether a clinically proven lifestyle modification program (LMP) in
      early pregnancy was superior to routine antenatal care in improving GDM, maternal
      and infant outcomes. Chinese pregnant women at risk of GDM (n = 220) were
      recruited at or before 12-week gestation and randomized to either a LMP group or
      a routine care control group. Eighty subjects completed a dietitian-led LMP
      including dietary and exercise components from early pregnancy till 24-week
      gestation. Data were compared with those of 86 control subjects. Twenty three
      (26.7%) control subjects and 20 (25.0%) LMP subjects developed GDM (p = 0.798).
      The proportion of infants born large for gestational age and macrosomia was
      similar between groups. The LMP group showed a lower proportion of excessive
      gestational weight gain (GWG). Subgroup analysis suggested that those with higher
      LMP adherence showed more desirable dietary composition and energy intake, and
      lower proportion of excessive GWG compared with the low LMP adherence group and
      the control group. The potential effect of LMP on GDM and other maternal and
      infant outcomes, in particular GWG, as well as barriers for making lifestyle
      changes warrant further investigations (ClinicalTrials.gov NCT02368600).

PMID- 30218013
TI  - Palmitoyl ascorbic acid 2-glucoside has the potential to protect mammalian cells
      from high-LET carbon-ion radiation.
AB  - DMSO, glycerol, and ascorbic acid (AA) are used in pharmaceuticals and known to
      display radioprotective effects. The present study investigates radioprotective
      properties of novel glyceryl glucoside, ascorbic acid 2-glucoside, glyceryl
      ascorbate, and palmitoyl ascorbic acid 2-glucoside (PA). Gamma-rays or high-LET
      carbon-ions were irradiated in the presence of tested chemicals. Lambda DNA
      damage, cell survival, and micronuclei formation of CHO cells were analyzed to
      evaluate radioprotective properties. Radiation-induced Lambda DNA damage was
      reduced with chemical pre-treatment in a concentration-dependent manner. This
      confirmed tested chemicals were radical scavengers. For gamma-irradiation,
      enhanced cell survival and reduction of micronuclei formation were observed for
      all chemicals. For carbon-ion irradiation, DMSO, glycerol, and PA displayed
      radioprotection for cell survival. Based on cell survival curves, protection
      levels by PA were confirmed and comparable between gamma-rays and high-LET carbon
      ions. Micronuclei formation was only decreased with AA and a high concentration
      of glycerol treatment, and not decreased with PA treatment. This suggests that
      mechanisms of protection against high-LET carbon-ions by PA can differ from
      normal radical scavenging effects that protect DNA from damage.

PMID- 30218014
TI  - Role of phosphate sensing in bone and mineral metabolism.
AB  - Inorganic phosphate (Pi) is essential for signal transduction and cell
      metabolism, and is also an essential structural component of the extracellular
      matrix of the skeleton. Pi is sensed in bacteria and yeast at the plasma
      membrane, which activates intracellular signal transduction to control the
      expression of Pi transporters and other genes that control intracellular Pi
      levels. In multicellular organisms, Pi homeostasis must be maintained in the
      organism and at the cellular level, requiring an endocrine and metabolic Pi
      sensing mechanism, about which little is currently known. This Review will
      discuss the metabolic effects of Pi, which are mediated by Pi transporters,
      inositol pyrophosphates and SYG1-Pho81-XPR1 (SPX)-domain proteins to maintain
      cellular phosphate homeostasis in the musculoskeletal system. In addition, we
      will discuss how Pi is sensed by the human body to regulate the production of
      fibroblast growth factor 23 (FGF23), parathyroid hormone and calcitriol to
      maintain serum levels of Pi in a narrow range. New findings on the crosstalk
      between iron and Pi homeostasis in the regulation of FGF23 expression will also
      be outlined. Mutations in components of these metabolic and endocrine phosphate
      sensors result in genetic disorders of phosphate homeostasis, cardiomyopathy and
      familial basal ganglial calcifications, highlighting the importance of this newly
      emerging area of research.

PMID- 30218015
TI  - Benefits of time-restricted feeding.

PMID- 30218017
TI  - Retraction Note: Formin' a perinuclear actin cage in confined migration.
AB  - Given that the authors of 'FMN2 makes perinuclear actin to protect nuclei during
      confined migration and promote metastasis' (Skau et al. Cell 167, 1571-1585;
      2016) have retracted their paper, I wish to retract this Research Highlight,
      which discussed the findings reported in that study.

PMID- 30218016
TI  - Recognition of Schizophrenia with Regularized Support Vector Machine and
      Sequential Region of Interest Selection using Structural Magnetic Resonance
      Imaging.
AB  - Structural brain abnormalities in schizophrenia have been well characterized with
      the application of univariate methods to magnetic resonance imaging (MRI) data.
      However, these traditional techniques lack sensitivity and predictive value at
      the individual level. Machine-learning approaches have emerged as potential
      diagnostic and prognostic tools. We used an anatomically and spatially
      regularized support vector machine (SVM) framework to categorize schizophrenia
      and healthy individuals based on whole-brain gray matter densities estimated
      using voxel-based morphometry from structural MRI scans. The regularized SVM
      model yielded recognition accuracy of 86.6% in the training set of 127
      individuals and validation accuracy of 83.5% in an independent set of 85
      individuals. A sequential region-of-interest (ROI) selection step was adopted for
      feature selection, improving recognition accuracy to 92.0% in the training set
      and 89.4% in the validation set. The combined model achieved 96.6% sensitivity
      and 74.1% specificity. Seven ROIs were identified as the optimal discriminatory
      subset: the occipital fusiform gyrus, middle frontal gyrus, pars opercularis of
      the inferior frontal gyrus, anterior superior temporal gyrus, superior frontal
      gyrus, left thalamus and left lateral ventricle. These findings demonstrate the
      utility of spatial and anatomical priors in SVM for neuroimaging analyses in
      conjunction with sequential ROI selection in the recognition of schizophrenia.

PMID- 30218018
TI  - A combination of curcumin and oligomeric proanthocyanidins offer superior anti
      tumorigenic properties in colorectal cancer.
AB  - Combining anti-cancer agents in cancer therapies is becoming increasingly popular
      due to improved efficacy, reduced toxicity and decreased emergence of resistance.
      Here, we test the hypothesis that dietary agents such as oligomeric
      proanthocyanidins (OPCs) and curcumin cooperatively modulate cancer-associated
      cellular mechanisms to inhibit carcinogenesis. By a series of in vitro assays in
      colorectal cancer cell lines, we showed that the anti-tumorigenic properties of
      the OPCs-curcumin combination were superior to the effects of individual
      compounds. By RNA-sequencing based gene-expression profiling in six colorectal
      cancer cell lines, we identified the cooperative modulation of key cancer
      associated pathways such as DNA replication and cell cycle pathways. Moreover,
      several pathways, including protein export, glutathione metabolism and porphyrin
      metabolism were more effectively modulated by the combination of OPCs and
      curcumin. We validated genes belonging to these pathways, such as HSPA5, SEC61B,
      G6PD, HMOX1 and PDE3B to be cooperatively modulated by the OPCs-curcumin
      combination. We further confirmed that the OPCs-curcumin combination more
      potently suppresses colorectal carcinogenesis and modulated expression of genes
      identified by RNA-sequencing in mice xenografts and in colorectal cancer patient
      derived organoids. Overall, by delineating the cooperative mechanisms of action
      of OPCs and curcumin, we make a case for the clinical co-administration of
      curcumin and OPCs as a treatment therapy for patients with colorectal cancer.

PMID- 30218019
TI  - Nicotine and sleep deprivation: impact on pain sensitivity and immune modulation
      in rats.
AB  - Repeated nicotine administration has been associated with increased paradoxical
      sleep in rats and antinociceptive properties, whereas paradoxical sleep
      deprivation (PSD) elicits pronociceptive and inflammatory responses. Thus, we
      aimed to evaluate the effect of repeated nicotine administration and its
      withdrawal combined with PSD on pain sensitivity and inflammatory markers. Sixty
      adult male Wistar rats were subjected to repeated injections of saline (SAL) or
      nicotine (NIC) for 12 days or 7 days of nicotine followed by acute mecamylamine
      administration on day 8 to precipitate nicotine abstinence (ABST). On day 9, the
      animals were submitted to PSD for 72 h or remained in control condition (CTRL);
      on day 12, thermal pain threshold was assessed by the hot plate test. PSD
      significantly decreased the latency to paw withdrawal in all groups compared to
      their respective controls. ABST-PSD animals presented higher levels of
      interleukin (IL)-6 compared to all groups, except ABST-CTRL. After adjustment for
      weight loss, IL-6, IL-4 and tumor necrosis factor alpha, ABST-PSD was associated
      with the lowest pain threshold. Nicotine and IL-4 levels were predictors of
      higher pain threshold. Hyperalgesia induced by PSD prevailed over the
      antinociceptive action of nicotine, while the association between PSD and ABST
      synergistically increased IL-6 concentrations and decreased pain threshold.

PMID- 30218020
TI  - Dynamic genomic architecture of mutualistic cooperation in a wild population of
      Mesorhizobium.
AB  - Research on mutualism seeks to explain how cooperation can be maintained when
      uncooperative mutants co-occur with cooperative kin. Gains and losses of the gene
      modules required for cooperation punctuate symbiont phylogenies and drive
      lifestyle transitions between cooperative symbionts and uncooperative free-living
      lineages over evolutionary time. Yet whether uncooperative symbionts commonly
      evolve from within cooperative symbiont populations or from within distantly
      related lineages with antagonistic or free-living lifestyles (i.e., third-party
      mutualism exploiters or parasites), remains controversial. We use genomic data to
      show that genotypes that differ in the presence or absence of large islands of
      symbiosis genes are common within a single wild recombining population of
      Mesorhizobium symbionts isolated from host tissues and are an important source of
      standing heritable variation in cooperation in this population. In a focal
      population of Mesorhizobium, uncooperative variants that lack a symbiosis island
      segregate at 16% frequency in nodules, and genome size and symbiosis gene number
      are positively correlated with cooperation. This finding contrasts with the
      genomic architecture of variation in cooperation in other symbiont populations
      isolated from host tissues in which the islands of genes underlying cooperation
      are ubiquitous and variation in cooperation is primarily driven by allelic
      substitution and individual gene gain and loss events. Our study demonstrates
      that uncooperative mutants within mutualist populations can comprise a
      significant component of genetic variation in nature, providing biological
      rationale for models and experiments that seek to explain the maintenance of
      mutualism in the face of non-cooperators.

PMID- 30218021
TI  - Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen)
      polymorphisms is influenced by the time of exposure to malaria.
AB  - Malaria has provided a major selective pressure and has modulated the genetic
      diversity of the human genome. The variants of the Duffy Antigen/Receptor for
      Chemokines (DARC) gene have probably been selected by malaria parasites,
      particularly the FY*O allele, which is fixed in sub-Saharan Africa and confers
      resistance to Plasmodium vivax infection. Here, we showed the influence of
      genomic ancestry on the distribution of DARC genotypes in a highly admixed
      Brazilian population and confirmed the decreased susceptibility of the FY*A/FY*O
      genotype to clinical P. vivax malaria. FY*B/FY*O individuals were associated with
      a greater risk of developing clinical malaria. A remarkable difference among DARC
      variants concerning the susceptibility to clinical malaria was more evident for
      individuals who were less exposed to malaria, as measured by the time of
      residence in the endemic area. Additionally, we found that DARC-negative and
      FY*A/FY*O individuals had a greater chance of acquiring high levels of antibodies
      against the 19-kDa C-terminal region of the P. vivax merozoite surface protein-1.
      Altogether, our results provide evidence that DARC polymorphisms modulate the
      susceptibility to clinical P. vivax malaria and influence the naturally-acquired
      humoral immune response to malaria blood antigens, which may interfere with the
      efficacy of a future vaccine against malaria.

PMID- 30218023
TI  - Plant growth-promoting rhizobacteria promote plant size inequality.
AB  - The uniformity of crop yield is extremely important for consumers and of as much
      relevance to the grower as overall yield. However, size inequality within a plant
      population is rarely measured and has never before been considered in relation to
      the use of beneficial microbes for yield enhancement. For the first time, we show
      that addition of soil bacteria to calabrese plants significantly increased size
      inequality. These effects were usually more apparent in above-ground biomass.
      This was caused by some (but not all) plants growing very large when inoculated
      with bacteria, while control plants were mostly small. We suggest that the main
      reason is the incompatibility of the inoculated bacteria with those already
      present in the rhizosphere. In some cases the inoculum matched the indigenous
      community, providing a benefit to plant growth, while often it did not and plants
      remained relatively small. We conclude that analyses of size inequality should be
      an integral part of experiments using microbial soil amendments. These analyses
      can help to inform the production of more effective microbial products and to
      ensure that the integration of beneficial microbes into sustainable production
      systems does not impair uniformity in yield.

PMID- 30218022
TI  - Genome-scale metabolic reconstructions of multiple Salmonella strains reveal
      serovar-specific metabolic traits.
AB  - Salmonella strains are traditionally classified into serovars based on their
      surface antigens. While increasing availability of whole-genome sequences has
      allowed for more detailed subtyping of strains, links between genotype, serovar,
      and host remain elusive. Here we reconstruct genome-scale metabolic models for
      410 Salmonella strains spanning 64 serovars. Model-predicted growth capabilities
      in over 530 different environments demonstrate that: (1) the Salmonella accessory
      metabolic network includes alternative carbon metabolism, and cell wall
      biosynthesis; (2) metabolic capabilities correspond to each strain's serovar and
      isolation host; (3) growth predictions agree with 83.1% of experimental outcomes
      for 12 strains (690 out of 858); (4) 27 strains are auxotrophic for at least one
      compound, including L-tryptophan, niacin, L-histidine, L-cysteine, and p
      aminobenzoate; and (5) the catabolic pathways that are important for fitness in
      the gastrointestinal environment are lost amongst extraintestinal serovars. Our
      results reveal growth differences that may reflect adaptation to particular
      colonization sites.

PMID- 30218024
TI  - Combining in silico and in vitro experiments to characterize the role of fascicle
      twist in the Achilles tendon.
AB  - The Achilles tendon (AT), the largest tendon in the human body has a unique
      structural feature, that is the fascicles in the AT display spiral twist.
      However, their functional and structural roles are still unclear. We used subject
      specific computational models and tissue mechanical experiment to quantitatively
      characterize the role of fascicle twist in the Achilles tendon. Ten subject
      specific finite element (FE) models of the Achilles tendon were developed from
      ultrasound images. Fascicle twist was implemented in these models using the
      material coordinate system available in our FE framework. Five different angles
      (0~60 degrees ) were implemented and material property optimization was performed
      for each of them (total 50 sets) using results from uniaxial stretch experiment.
      We showed that fascicle twist allows for even distribution of stress across the
      whole tendon, thus improving tissue strength. The predicted rupture load
      increased up to 40%. A number of connective tissues display similar fascicle
      twists in their structure. The resulting non-uniform strain distribution has been
      hypothesized as a primary factor in tissue degeneration and injuries. Therefore,
      our technique will be used to design biomechanically informed training and
      rehabilitation protocols for management of connective tissue injuries and
      degeneration.

PMID- 30218025
TI  - Mechanisms, biomarkers and targets for adult-onset Still's disease.
AB  - Adult-onset Still's disease (AoSD) is a rare but clinically well-known,
      polygenic, systemic autoinflammatory disease. Owing to its sporadic appearance in
      all adult age groups with potentially severe inflammatory onset accompanied by a
      broad spectrum of disease manifestation and complications, AoSD is an unsolved
      challenge for clinicians with limited therapeutic options. This Review provides a
      comprehensive insight into the complex and heterogeneous nature of AoSD,
      describing biomarkers of the disease and its progression and the cytokine
      signalling pathways that contribute to disease. The efficacy and safety of
      biologic therapeutic options are also discussed, and guidance for treatment
      decisions is provided. Improving the approach to AoSD in the future will require
      much closer cooperation between paediatric and adult rheumatologists to establish
      common diagnostic strategies, treatment targets and goals.

PMID- 30218026
TI  - Superconducting Phases in Lithium Decorated Graphene LiC6.
AB  - A study of possible superconducting phases of graphene has been constructed in
      detail. A realistic tight binding model, fit to ab initio calculations, accounts
      for the Li-decoration of graphene with broken lattice symmetry, and includes s
      and d symmetry Bloch character that influences the gap symmetries that can arise.
      The resulting seven hybridized Li-C orbitals that support nine possible bond
      pairing amplitudes. The gap equation is solved for all possible gap symmetries.
      One band is weakly dispersive near the Fermi energy along Gamma -> M where its
      Bloch wave function has linear combination of [Formula: see text] and dxy
      character, and is responsible for [Formula: see text] and dxy pairing with lowest
      pairing energy in our model. These symmetries almost preserve properties from a
      two band model of pristine graphene. Another part of this band, along K -> Gamma,
      is nearly degenerate with upper s band that favors extended s wave pairing which
      is not found in two band model. Upon electron doping to a critical chemical
      potential MU1 = 0.22 eV the pairing potential decreases, then increases until a
      second critical value MU2 = 1.3 eV at which a phase transition to a distorted s
      wave occurs. The distortion of d- or s-wave phases are a consequence of
      decoration which is not appear in two band pristine model. In the pristine
      graphene these phases convert to usual d-wave or extended s-wave pairing.

PMID- 30218028
TI  - Immunogenomic features of mCRPC revealed.

PMID- 30218027
TI  - PD-1 mRNA predicts response to therapy.

PMID- 30218029
TI  - Erlotinib effective in the neoadjuvant setting.

PMID- 30218030
TI  - Precision risk-based screening might maximize benefit and minimize harm.

PMID- 30218031
TI  - Different multi-year mean temperature in mid-summer of South China under
      different 1.5  degrees C warming scenarios.
AB  - The Paris Agreement proposed a goal of "pursuing efforts to limit the temperature
      increase to 1.5  degrees C above pre-industrial levels". The Community Earth
      System Model, version 1, with the Community Atmosphere Model, version 5 (CESM1
      CAM5), designed a set of experiments that fulfilled the 1.5  degrees C warming
      goal. By analyzing the outputs, this study aims to present projections associated
      with warming in South China (SC). Interestingly, if the global mean temperature
      (GMT) overshoots to 1.7  degrees C above the pre-industrial levels in 2050 and
      back to 1.5  degrees C by 2100, additional warming in the SC mid-summer will
      occur when approaching 2100 compared to that in the scenario under which the GMT
      stabilizes at an increase of 1.5  degrees C after the mid-2040 s. In the final 1
      to 3 decades of 21st century in most parts of SC, the multi-year mean warming
      differences, as well as the difference of extreme hot days, between the two
      scenarios are significant among the ensembles in mid-summer. Under the scenario
      in which the GMT overshoots an increase of 1.5  degrees C, the decrease of mid
      level clouds leads to increased downwards solar radiation in the SC and warms the
      surface, resulting in increases in both outgoing longwave radiation and latent
      heat flux into the atmosphere and maintenance of the surface balance of the heat
      budget.

PMID- 30218032
TI  - Diminished TLR2-TLR9 mediated CD4+ T cell responses are associated with increased
      inflammation in intraocular tuberculosis.
AB  - Intraocular tuberculosis (IOTB) is amongst the leading causes of uveitis in
      tropical countries. Despite reports on involvement of proinflammatory cytokines,
      studies on innate immune responses in disease pathogenesis are lacking. Reports
      from animal models and patients with pulmonary tuberculosis indicate that defects
      in toll like receptor (TLR)2 and TLR9 signalling predispose them to tuberculosis.
      In this context, we investigated the role of TLR2, TLR4 and TLR9 in generation of
      CD4+ T effector (Teff) cell responses during IOTB. Firstly, the cells in vitreous
      fluids showed lower expression of TLR2 and TLR9 in IOTB as compared to non
      uveitis and non-TB uveitis groups. Next, peripheral CD4+ Teff cells of subjects
      with IOTB showed decreased proliferative responses and lower induction of Tregs
      following TLR2 and TLR9 stimulation. Further, TLR9 ligation resulted in increased
      IFN-gamma and IL-17a but decreased expression of IL-10 and TGF-beta. Lastly,
      lower expression of genes involved in TLR9 signalling after direct TLR9 ligation
      was observed in IOTB. Collectively, our results show that a subdued response to
      direct TLR2 and TLR9 stimulation in CD4+ T cells is associated with increased
      proinflammatory responses in IOTB. These findings reveal an important link
      between innate immune signalling and ensuing adaptive immune responses in IOTB
      with implications in other forms of extrapulmonary tuberculosis.

PMID- 30218033
TI  - Assessment of the impacts of climatic variability and anthropogenic stress on
      hydrologic resilience to warming shifts in Peninsular India.
AB  - Most parts of the world are witnessing climatic warming and the trend is expected
      to increase in the future. It is important to assess the response of watershed
      hydrology to this warming. Moreover, human interactions and climatic variability
      influence the water balance of a catchment. We perform contribution analysis
      along with resilience study using Budyko framework and two parameters (dynamic
      deviation and modified elasticity), in-order to comprehend the involvement of
      anthropogenic stress and climatic variance on partitioning of precipitation and
      their relation with hydrologic resilience to warming shifts across 55 catchments
      in peninsular India. Here, 23 catchments have displayed hydrologic resilience
      (low departure and high elasticity) to climatic warming shifts. Only 37.14% of
      anthropogenic dominated catchments (higher contribution from human activities in
      runoff changes) were found to be resilient whereas 58.82% of climate dominated
      catchments had resilience attributes. Most of the catchments on western and
      extreme southern part of India were not hydrologic resilient. Extensive human
      interactions tend to depart the catchment from expected hydrological functioning
      under critical climatic conditions (Warming in our study) that lead to declining
      of hydrological resilience.

PMID- 30218034
TI  - UPF1-like helicase grip on nucleic acids dictates processivity.
AB  - Helicases are molecular engines which translocate along nucleic acids (NA) to
      unwind double-strands or remodel NA-protein complexes. While they have an
      essential role in genome structure and expression, the rules dictating their
      processivity remain elusive. Here, we developed single-molecule methods to
      investigate helicase binding lifetime on DNA. We found that UPF1, a highly
      processive helicase central to nonsense-mediated mRNA decay (NMD), tightly holds
      onto NA, allowing long lasting action. Conversely, the structurally similar
      IGHMBP2 helicase has a short residence time. UPF1 mutants with variable grip on
      DNA show that grip tightness dictates helicase residence time and processivity.
      In addition, we discovered via functional studies that a decrease in UPF1 grip
      impairs NMD efficiency in vivo. Finally, we propose a three-state model with
      bound, sliding and unbound molecular clips, that can accurately predict the
      modulation of helicase processivity.

PMID- 30218035
TI  - In vitro protein expression changes in RAW 264.7 cells and HUVECs treated with
      dialyzed coffee extract by immunoprecipitation high performance liquid
      chromatography.
AB  - RAW 264.7 cells and HUVECs were compared to evaluate the effects of dialyzed
      coffee extract (DCE) and artificial coffee (AC). Immunoprecipitation high
      performance liquid chromatography (IP-HPLC) showed DCE-2.5- (equivalent to 2.5
      cups of coffee a day) and DCE-5-induced protein expression that was beneficial to
      human health, i.e., they led to significant increases in proliferation-, immunity
      , cellular protection-, antioxidant signaling-, and osteogenesis-related proteins
      but decreases in inflammation-, NFkB signaling-, cellular apoptosis-, and
      oncogenic signaling-related proteins in RAW 264.7 cells, and slight decreases in
      angiogenesis-related proteins in HUVECs. These protein expression changes were
      less frequently observed for DCE-10 treatment, while AC treatment induced very
      different changes in protein expression. We suggest that the favorable cellular
      effects of DCE were derived from minor coffee elements that were absent in AC,
      and that the reduced effects of DCE-10 compared with those of DCE-2.5 or DCE-5
      might have been caused by greater adverse reactions to caffeine and chlorogenic
      acid in DCE-10 than DCE-2.5 or DCE-5. IP-HPLC results suggested that minor coffee
      elements in DCE might play beneficial roles in the global protein expression of
      proliferation-, immunity-, anti-inflammation-, cell protection-, antioxidant-,
      anti-apoptosis-, anti-oncogenesis-, and osteogenesis-related proteins in RAW
      264.7 cells and enhance anti-angiogenic signaling in HUVECs.

PMID- 30218037
TI  - Urinary cell-free DNA and UTI; the age of 'omics'.

PMID- 30218038
TI  - New phenoxazinone-related alkaloids from strain Streptomyces sp. KIB-H1318.
AB  - Chemical investigation of a strain Streptomyces sp. KIB-H1318 isolated from soil
      sample led to the discovery of three new phenoxazinone-related alkaloids 1-3, as
      well as two known analogs exfoliazone (4) and viridobrunnine A (5). Their
      structures were determined on the basis of extensive spectroscopic analysis. The
      antimicrobial activity and cytotoxicity of the isolates were assayed. Exfoliazone
      and viridobrunnine A exhibited minor antibacterial activity against Escherichia
      coli ATCC 8099, Bacillus subtilis ATCC 6633, and Staphylococcus aureus ATCC 6538.
      Compound 2 exhibited low cytotoxicity against two human cancer cell lines HeLa
      and SW480 with the IC50 values of 36.8 and 37.8 MUM, respectively.

PMID- 30218039
TI  - Late Pleistocene glacial transitions in North America altered major river
      drainages, as revealed by deep-sea sediment.
AB  - Sediment eroded from continents during ice ages can be rapidly (<104 years)
      transferred via rivers to the deep-sea and preserved in submarine fans, becoming
      a viable record of landscape evolution. We applied chemical weathering proxies
      and zircon geo-thermo-chronometry to late Pleistocene sediment recovered from the
      deep-sea Mississippi fan, revealing interactions between the Laurentide ice sheet
      (LIS) and broader Mississippi-Missouri catchment between ca. 70,000 and 10,000
      years ago (70 to 10 ka). Sediment contribution from the Missouri catchment to the
      Mississippi fan was low between 70 and 30 ka but roughly doubled after the Last
      Glacial Maximum (LGM). Therefore, pre-LGM glacial advance profoundly altered the
      vast Missouri drainage through ice dams and/or re-routing of the river, thereby
      controlling the transfer of continental debris and freshwater toward southern
      outlets.

PMID- 30218041
TI  - Cells with stemness features are generated from in vitro transformed human
      fibroblasts.
AB  - Cancer stem cells (CSCs) have been involved in the maintenance, progression and
      relapse of several tumors, but their origin is still elusive. Here, in vitro
      transformed human fibroblasts (cen3tel cells) and the tumorsphere assay were used
      to search for and possibly characterize CSCs in transformed somatic cells.
      Cen3tel cells formed spheres showing self-renewal capacity and Sox2
      overexpression, suggesting that they contained a subset of cells with CSC-like
      features. Sphere cells displayed deregulation of a c-MYC/miR-34a circuitry,
      likely associated with cell protection from apoptosis. Gene expression profiles
      of sphere cells revealed an extensive transcriptional reprogramming. Genes up
      regulated in tumorspheres identified processes related to tumorigenesis and
      stemness, as cholesterol biosynthesis, apoptosis suppression, interferon and
      cytokine mediated signalling pathways. Sphere cells engrafted into NSG mice more
      rapidly than adherent cells, but both cell populations were tumorigenic. These
      results indicate that, during transformation, human somatic cells can acquire CSC
      properties, confirming the high plasticity of tumor cells. However, CSC-like
      cells are not the only tumorigenic population in transformed cells, indicating
      that the CSC phenotype and tumorigenicity can be uncoupled.

PMID- 30218042
TI  - Communities at the centre.

PMID- 30218043
TI  - Filming flagella and pili in action.

PMID- 30218040
TI  - Autosomal genetic variation is associated with DNA methylation in regions
      variably escaping X-chromosome inactivation.
AB  - X-chromosome inactivation (XCI), i.e., the inactivation of one of the female X
      chromosomes, restores equal expression of X-chromosomal genes between females and
      males. However, ~10% of genes show variable degrees of escape from XCI between
      females, although little is known about the causes of variable XCI. Using a
      discovery data-set of 1867 females and 1398 males and a replication sample of
      3351 females, we show that genetic variation at three autosomal loci is
      associated with female-specific changes in X-chromosome methylation. Through cis
      eQTL expression analysis, we map these loci to the genes SMCHD1/METTL4,
      TRIM6/HBG2, and ZSCAN9. Low-expression alleles of the loci are predominantly
      associated with mild hypomethylation of CpG islands near genes known to variably
      escape XCI, implicating the autosomal genes in variable XCI. Together, these
      results suggest a genetic basis for variable escape from XCI and highlight the
      potential of a population genomics approach to identify genes involved in XCI.

PMID- 30218044
TI  - The Thaumarchaeon N. gargensis carries functional bioABD genes and has a
      promiscuous E. coli DeltabioH-complementing esterase EstN1.
AB  - Biotin is an essential cofactor required for carboxylation and decarboxylation
      reactions in all domains of life. While biotin biosynthesis in most Bacteria and
      Eukarya is well studied, the complete pathway for this vitamer in Archaea is
      still not known. Detailed genome searches indicated the presence of possible bio
      gene clusters only in Methanococcales and Thaumarchaeota. Therefore, we analysed
      the functionality of the predicted genes bioA, bioB, bioD and bioF in the
      Thaumarchaeon Nitrososphaera gargensis Ga2.9 which are essential for the later
      steps of biotin synthesis. In complementation tests, the gene cluster-encoded N.
      gargensis bioABD genes except bioF restored growth of corresponding E. coli
      Rosetta-gami 2 (DE3) deletion mutants. To find out how biotin biosynthesis is
      initiated, we searched the genome for a possible bioH analogue encoding a
      pimeloyl-ACP-methylester carboxylesterase. The respective amino acid sequence of
      the ORF estN1 showed weak conserved domain similarity to this class of enzymes (e
      value 3.70e-42). Remarkably, EstN1 is a promiscuous carboxylesterase that
      complements E. coli DeltabioH and Mesorhizobium loti DeltabioZ mutants for growth
      on biotin-free minimal medium. Additional 3D-structural models support the
      hypothesis that EstN1 is a BioH analogue. Thus, this is the first report
      providing experimental evidence that Archaea carry functional bio genes.

PMID- 30218045
TI  - Ear transplantations reveal conservation of inner ear afferent pathfinding cues.
AB  - Vertebrate inner ear neurons project into the correct brainstem nuclei region
      before target neurons become postmitotic, or even in their absence. Moreover,
      afferents from transplanted ears in frogs have been shown to navigate to
      vestibular nuclei, suggesting that ear afferents use molecular cues to find their
      target. We performed heterochronic, xenoplastic, and heterotopic transplantations
      in chickens to investigate whether inner ear afferents are guided by conserved
      guidance molecules. We show that inner ear afferents can navigate to the
      vestibular nuclei following a delay in afferent entry and when the ear was from a
      different species, the mouse. These data suggest that guidance molecules are
      expressed for some time and are conserved across amniotes. In addition, we show
      that chicken ears transplanted adjacent to the spinal cord project dorsally like
      in the hindbrain. These results suggest that inner ear afferents navigate to the
      correct dorsoventral brainstem column using conserved cues.

PMID- 30218047
TI  - Nanoparticles reveal Extreme Size-Sorting and Morphologies in Complex Coacervate
      Superstructures.
AB  - We here provide detailed insight in self-assembled complex coacervate systems
      exploiting gold nanoparticles for cryoTEM contrast. Nanoparticle-containing
      dendrimicelles are formed from fifth-generation dendrimer-encapsulated
      nanoparticles (DENs) and dendrimer-stabilized nanoparticles (DSNs). The complex
      coacervate structures self-organize in biconcave thin water layers into size
      sorted monolayer superstructures. The embedded nanoparticles are a
      straightforward tool to visualize dendrimicelles and determine the aggregation
      number and polydispersity. The superstructure shows extreme size-sorting patterns
      which, contrary to related systems with higher generation dendrimers, consists
      not only of dendrimicelles but also much bigger complex coacervate
      nanoassemblies, such as vesicles.

PMID- 30218046
TI  - The gut microbiota promotes hepatic fatty acid desaturation and elongation in
      mice.
AB  - Interactions between the gut microbial ecosystem and host lipid homeostasis are
      highly relevant to host physiology and metabolic diseases. We present a
      comprehensive multi-omics view of the effect of intestinal microbial colonization
      on hepatic lipid metabolism, integrating transcriptomic, proteomic,
      phosphoproteomic, and lipidomic analyses of liver and plasma samples from
      germfree and specific pathogen-free mice. Microbes induce monounsaturated fatty
      acid generation by stearoyl-CoA desaturase 1 and polyunsaturated fatty acid
      elongation by fatty acid elongase 5, leading to significant alterations in
      glycerophospholipid acyl-chain profiles. A composite classification score
      calculated from the observed alterations in fatty acid profiles in germfree mice
      clearly differentiates antibiotic-treated mice from untreated controls with high
      sensitivity. Mechanistic investigations reveal that acetate originating from gut
      microbial degradation of dietary fiber serves as precursor for hepatic synthesis
      of C16 and C18 fatty acids and their related glycerophospholipid species that are
      also released into the circulation.

PMID- 30218049
TI  - Sex differences and the prognosis of depressive and nondepressive patients with
      cardiovascular risk factors: the Japan Morning Surge-Home Blood Pressure (J-HOP)
      study.
AB  - Depression is associated with mortality in patients with cardiovascular risk
      factors. The frequency and severity of depression and the association between
      depression and cardiovascular events have sex-specific and ethnic differences. We
      conducted this study to evaluate the sex-specific difference in the association
      between depression and cardiovascular prognosis in patients with cardiovascular
      risk factors. We enrolled 4025 patients (64.7 +/- 10.9 years, 53% women, 47% men)
      with cardiovascular risk factors in the Japan Morning Surge-Home Blood Pressure
      study. Depressive symptoms were assessed using the Beck Depression Inventory
      (BDI). The follow-up period was 47 +/- 24 months. The primary end points were all
      cause mortality and nonfatal cardiovascular events. The BDI scores and the
      prevalence of depression were significantly higher in women than in men. When a
      BDI score of 16 was the cutoff, the primary end points in the depression group (n
      = 217) were significantly higher than those in the nondepression group (n = 1677)
      among men (adjusted hazard ratio 1.76, 95% confidence interval: 1.17, 2.64; P =
      0.007). In women, the primary end points in the depression and nondepression
      groups were similar when BDI scores of 16, 14, and 10 were the cutoffs. In
      conclusion, depression defined by a BDI score >=16 was associated with
      cardiovascular events in men with cardiovascular risk factors.

PMID- 30218048
TI  - Rare-earth fluorescence thermometry of laser-induced plasmon heating in silver
      nanoparticles arrays.
AB  - The laser-induced plasmon heating of an ordered array of silver nanoparticles,
      under continuous illumination with an Ar laser, was probed by rare-earth
      fluorescence thermometry. The rise in temperature in the samples was monitored by
      measuring the temperature-sensitive photoluminescent emission of a europium
      complex (EuTTA) embedded in PMMA thin-films, deposited onto the nanoparticles
      array. A maximum temperature increase of 19  degrees C was determined upon
      resonant illumination with the surface plasmon resonance of the nanoarray at the
      highest pump Ar laser power (173 mW). The experimental results were supported by
      finite elements method electrodynamic simulations, which provided also
      information on the temporal dynamics of the heating process. This method proved
      to be a facile and accurate approach to probe the actual temperature increase due
      to photo-induced plasmon heating in plasmonic nanosystems.

PMID- 30218050
TI  - Association between socioeconomic factors and urinary sodium-to-potassium ratio:
      the Nagahama Study.
AB  - High sodium intake is a simple modifiable risk factor for hypertension. Although
      not confirmed, lower socioeconomic status may be a factor that increases sodium
      intake. We aimed to clarify the association between socioeconomic status and
      urinary sodium-to-potassium ratio by cross-sectional and longitudinal analyses.
      The study included 9410 community residents. Spot urine sodium-to-potassium
      ratios were measured twice with a 5-year interval. Socioeconomic status was
      investigated using a self-administered questionnaire. Cross-sectional analysis
      revealed that educational attainment was inversely associated with urinary sodium
      to-potassium ratio (years of education <= 9: 3.0 +/- 1.8, <= 12: 2.9 +/- 1.6, >=
      13: 2.8 +/- 1.6; P < 0.001), whereas no significant association was observed with
      household income. Men, particularly individuals living alone, exhibited markedly
      high sodium-to-potassium ratios (3.6 +/- 2.3). Although frequent intake of
      vegetables, fruits, and dairy products was also inversely associated with the
      ratio, the associations with educational attainment ( <= 9: reference, <= 12:
      beta = -0.032, P = 0.026, >= 13: beta = -0.059, P < 0.001), marital status (beta
      = -0.040, P < 0.001), and sex*marital status interaction (beta = 0.054, P =
      0.001) were independent of these covariates. Educational attainment was also
      inversely associated with differences in the urinary sodium-to-potassium ratio
      during the follow-up period (odds ratio, 0.70; P < 0.001). Lower educational
      attainment was an independent determinant for urinary sodium-to-potassium ratio.
      Health literacy education, particularly in men living alone, may be a factor for
      reducing salt intake even in high-income countries where equal educational
      opportunity is assured.

PMID- 30218051
TI  - The last-born daughter cell contributes to division orientation of Drosophila
      larval neuroblasts.
AB  - Controlling the orientation of cell division is important in the context of cell
      fate choices and tissue morphogenesis. However, the mechanisms providing the
      required positional information remain incompletely understood. Here we use stem
      cells of the Drosophila larval brain that stably maintain their axis of polarity
      and division between cell cycles to identify cues that orient cell division.
      Using live cell imaging of cultured brains, laser ablation and genetics, we
      reveal that division axis maintenance relies on their last-born daughter cell. We
      propose that, in addition to known intrinsic cues, stem cells in the developing
      fly brain are polarized by an extrinsic signal. We further find that division
      axis maintenance allows neuroblasts to maximize their contact area with glial
      cells known to provide protective and proliferative signals to neuroblasts.

PMID- 30218053
TI  - Rapid Adaptation to the Timbre of Natural Sounds.
AB  - Timbre, the unique quality of a sound that points to its source, allows us to
      quickly identify a loved one's voice in a crowd and distinguish a buzzy, bright
      trumpet from a warm cello. Despite its importance for perceiving the richness of
      auditory objects, timbre is a relatively poorly understood feature of sounds.
      Here we demonstrate for the first time that listeners adapt to the timbre of a
      wide variety of natural sounds. For each of several sound classes, participants
      were repeatedly exposed to two sounds (e.g., clarinet and oboe, male and female
      voice) that formed the endpoints of a morphed continuum. Adaptation to timbre
      resulted in consistent perceptual aftereffects, such that hearing sound A
      significantly altered perception of a neutral morph between A and B, making it
      sound more like B. Furthermore, these aftereffects were robust to moderate pitch
      changes, suggesting that adaptation to timbral features used for object
      identification drives these effects, analogous to face adaptation in vision.

PMID- 30218052
TI  - Ketamine reduces aversion in rodent pain models by suppressing hyperactivity of
      the anterior cingulate cortex.
AB  - Chronic pain is known to induce an amplified aversive reaction to peripheral
      nociceptive inputs. This enhanced affective response constitutes a key pathologic
      feature of chronic pain syndromes such as fibromyalgia. However, the neural
      mechanisms that underlie this important aspect of pain processing remain poorly
      understood, hindering the development of treatments. Here, we show that a single
      dose of ketamine can produce a persistent reduction in the aversive response to
      noxious stimuli in rodent chronic pain models, long after the termination of its
      anti-nociceptive effects. Furthermore, we demonstrated that this anti-aversive
      property is mediated by prolonged suppression of the hyperactivity of neurons in
      the anterior cingulate cortex (ACC), a brain region well known to regulate pain
      affect. Therefore, our results indicate that it is feasible to dissociate the
      affective from the sensory component of pain, and demonstrate the potential for
      low-dose ketamine to be an important therapy for chronic pain syndromes.

PMID- 30218054
TI  - Nonreciprocal responses from non-centrosymmetric quantum materials.
AB  - Directional transport and propagation of quantum particle and current, such as
      electron, photon, spin, and phonon, are known to occur in the materials system
      with broken inversion symmetry, as exemplified by the diode in semiconductor p-n
      junction and the natural optical activity in chiral materials. Such a
      nonreciprocal response in the quantum materials of noncentrosymmetry occurs
      ubiquitously when the time-reversal symmetry is further broken by applying a
      magnetic field or with spontaneous magnetization, such as the magnetochiral
      effect and the nonreciprocal magnon transport or spin current in chiral magnets.
      In the nonlinear regime responding to the square of current and electric field,
      even a more variety of nonreciprocal phenomena can show up, including the
      photocurrent of topological origin and the unidirectional magnetoresistance in
      polar/chiral semiconductors. Microscopically, these nonreciprocal responses in
      the quantum materials are frequently encoded by the quantum Berry phase, the
      toroidal moment, and the magnetoelectric monopole, thus cultivating the fertile
      ground of the functional topological materials. Here, we review the basic
      mechanisms and emergent phenomena and functions of the nonreciprocal responses in
      the noncentrosymmetric quantum materials.

PMID- 30218055
TI  - Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates
      osteoarthritis progression in mice through induction of IL-10.
AB  - Osteoarthritis (OA) is a major degenerative joint condition that causes articular
      cartilage destruction. It was recently found that enhancement of chondroclasts
      and suppression in Treg cell differentiation are involved in the pathogenesis of
      OA. Kartogenin (KGN) is a small drug-like molecule that induces chondrogenesis in
      mesenchymal stem cells (MSCs). This study aimed to identify whether KGN can
      enhance severe pain behavior and improve cartilage repair in OA rat model.
      Induction of OA model was loaded by IA-injection of MIA. In the OA rat model,
      treatment an intra-articular injection of KGN. Pain levels were evaluated by
      analyzing PWL and PWT response in animals. Histological analysis and micro-CT
      images of femurs were used to analyze cartilage destruction. Gene expression was
      measured by real-time PCR. Immunohistochemistry was analyzed to detect protein
      expression. KGN injection significantly decreased pain severity and joint
      destruction in the MIA-induced OA model. KGN also increased mRNA levels of the
      anti-inflammatory cytokine IL-10 in OA patients' chondrocytes stimulated by IL
      1beta. Decreased chondroclast expression, and increased Treg cell expression. KGN
      revealed therapeutic activity with the potential to reduce pain and improve
      cartilage destruction. Thus, KGN could be a therapeutic molecule for OA that
      inhibits cartilage damage.

PMID- 30218056
TI  - Evidence for the beneficial effect of perceptual grouping on visual working
      memory: an empirical study on illusory contour and a meta-analytic study.
AB  - The capacity of visual working memory (VWM) is found to be extremely limited.
      Past research shows that VWM can be facilitated by Gestalt principles of
      grouping, however, it remains controversial whether factors like the type of
      Gestalt principles, the characteristics of stimuli and the nature of experimental
      design could affect the beneficial effect of grouping. In particular, studies
      have shown that perceptual grouping could improve memory performance for a
      feature that is relevant for grouping, but it is unclear whether the same
      improvement exists for a feature that is irrelevant for grouping. In this
      article, an empirical study and a meta-analytic study were conducted to
      investigate the effect of perceptual grouping on VWM. In the empirical study, we
      examined the grouping effect by employing a Kanizsa illusion in which memory
      items were grouped by illusory contour. We found that the memory performance was
      improved for the grouped items even though the tested feature was grouping
      irrelevant, and the improvement was not significantly different from the effect
      of grouping by physical connectedness or by solid occlusion. In the meta-analytic
      study, we systematically and quantitatively examined the effect of perceptual
      grouping on VWM by pulling the results from all eligible studies, and found that
      the beneficial grouping effect was robust but the magnitude of the effect can be
      affected by several moderators. Factors like the types of grouping methods, the
      duration and the layout of the memory display, and the characteristics of the
      tested feature moderated the grouping effect, whereas whether employing a cue or
      a verbal suppression task did not. Our study suggests that the underlying
      mechanism of the grouping benefit may be distinct with regard to grouping
      relevancy of the to-be-stored feature. The grouping effect on VWM may be
      independent of attention for a grouping relevant feature, but may rely on
      attentional prioritization for a grouping irrelevant feature.

PMID- 30218057
TI  - Deep Brain Stimulation for Parkinson's disease changes perception in the Rubber
      Hand Illusion.
AB  - Parkinson's disease (PD) alters cortico-basal ganglia-thalamic circuitry and
      susceptibility to an illusion of bodily awareness, the Rubber Hand Illusion
      (RHI). Bodily awareness is thought to result from multisensory integration in a
      predominantly cortical network; the role of subcortical connections is unknown.
      We studied the effect of modulating cortico-subcortical circuitry on multisensory
      integration for bodily awareness in 24 PD patients treated with subthalamic
      nucleus (STN) deep brain stimulation (DBS), in comparison to 21 healthy
      volunteers, using the RHI experiment. Typically, synchronous visuo-tactile cues
      induce a false perception of touch on the rubber hand as if it were the subject's
      hand, whereas asynchronous visuo-tactile cues do not. However, we found that in
      the asynchronous condition, patients in the off-stimulation state did not reject
      the RHI as strongly as healthy controls; patients' rejection of the RHI
      strengthened when STN-DBS was switched on, although it remained weaker than that
      of controls. Patients in the off-stimulation state also misjudged the position of
      their hand, indicating it to be closer to the rubber hand than controls. However,
      STN-DBS did not affect proprioceptive judgements or subsequent arm movements
      altered by the perceptual effects of the illusion. Our findings support the idea
      that the STN and subcortical connections have a key role in multisensory
      integration for bodily awareness. Decision-making in multisensory bodily
      illusions is discussed.

PMID- 30218058
TI  - Skeletal Muscle Dystrophy mutant of lamin A alters the structure and dynamics of
      the Ig fold domain.
AB  - Mutations in the different domains of A-type lamin proteins cause a diverse
      plethora of diseases collectively termed as laminopathies which can affect
      multiple organs. Ig fold is one such domain of lamin A which is implicated in
      numerous nuclear interactions wherein the mutations lead to different
      laminopathies. W514R is one such mutation in the Ig fold which leads to severe
      phenotypes in Skeletal Muscle Dystrophy (SMD) which is a class of laminopathies.
      In this report, we elucidated gross alterations in structure and dynamics at the
      level of individual amino acids. These studies indicate altered conformational
      features of residues in the close vicinity of W514. Imaging of mammalian cells
      transfected with the mutant have shown distinct perturbation of the nuclear
      meshwork with concomitant alteration in nuclear interactions as a result of
      increased oligomerization of Ig W514R. Hence, this novel approach of amalgamating
      theoretical and experimental procedures to predict the severity of a mutant in
      the context of laminopathies could be extended for numerous lamin A mutants.

PMID- 30218060
TI  - cGAS activation in phased droplets.

PMID- 30218059
TI  - Small, Long Blood Half-Life Iodine Nanoparticle for Vascular and Tumor Imaging.
AB  - Standard clinical X-ray contrast agents are small iodine-containing molecules
      that are rapidly cleared by the kidneys and provide robust imaging for only a few
      seconds, thereby limiting more extensive vascular and tissue biodistribution
      imaging as well as optimal tumor uptake. They are also not generally useful for
      preclinical microCT imaging where longer scan times are required for high
      resolution image acquisition. We here describe a new iodine nanoparticle contrast
      agent that has a unique combination of properties: 20 nm hydrodynamic diameter,
      covalent PEG coating, 40 hour blood half-life, 50% liver clearance after six
      months, accumulation in tumors, and well-tolerated to at least 4 g iodine/kg body
      weight after intravenous administration in mice. These characteristics are unique
      among the other iodine nanoparticles that have been previously reported and
      provide extended-time high contrast vascular imaging and tumor loading. As such,
      it is useful for preclinical MicroCT animal studies. Potential human applications
      might include X-ray radiation dose enhancement for cancer therapy and vascular
      imaging for life-threatening situations where high levels of contrast are needed
      for extended periods of time.

PMID- 30218061
TI  - Staged profiling of sperm development in sync.

PMID- 30218063
TI  - Macrophage-secreted interleukin-35 regulates cancer cell plasticity to facilitate
      metastatic colonization.
AB  - A favorable interplay between cancer cells and the tumor microenvironment (TME)
      facilitates the outgrowth of metastatic tumors. Because of the distinct
      initiating processes between primary and metastatic tumors, we investigate the
      differences in tumor-associated macrophages (TAMs) from primary and metastatic
      cancers. Here we show that dual expression of M1 and M2 markers is noted in TAMs
      from primary tumors, whereas predominant expression of M2 markers is shown in
      metastatic TAMs. At metastatic sites, TAMs secrete interleukin-35 (IL-35) to
      facilitate metastatic colonization through activation of JAK2-STAT6-GATA3
      signaling to reverse epithelial-mesenchymal transition (EMT) in cancer cells. In
      primary tumors, inflammation-induced EMT upregulates IL12Rbeta2, a subunit of the
      IL-35 receptor, in cancer cells to help them respond to IL-35 during metastasis.
      Neutralization of IL-35 or knockout of IL-35 in macrophages reduces metastatic
      colonization. These results indicate the distinct TMEs of primary and metastatic
      tumors and provide potential targets for intercepting metastasis.

PMID- 30218062
TI  - Effect of adjunctive single high-dose vitamin D3 on outcome of community-acquired
      pneumonia in hospitalised adults: The VIDCAPS randomised controlled trial.
AB  - Low vitamin D status is associated with increased risk of pneumonia, greater
      disease severity and poorer outcome. However, no trials have examined the effect
      of adjunctive vitamin D therapy on outcomes in adults with community-acquired
      pneumonia (CAP). We conducted a randomised, double-blind, placebo-controlled
      trial examining the effects of adjunctive vitamin D in adults hospitalised with
      CAP. Participants were randomised to either a single oral dose of 200,000 IU
      vitamin D3 or placebo. The primary outcome was the complete resolution of chest
      radiograph infiltrate at 6 weeks post-study treatment. Secondary outcomes
      included length of hospital stay, intensive care admission and return to normal
      activity. Only participants who completed the study or died within the 6 week
      period were included in the analysis (n = 60 vitamin D, n = 57 placebo).
      Adjunctive vitamin D did not have any effect on the primary outcome (OR 0.78, 95%
      CI 0.31 to 1.86, p = 0.548). However, there was evidence it increased the
      complete resolution of pneumonia in participants with baseline vitamin D levels
      <25 nmol/L (OR 17.0, 95% CI 1.40-549.45, P = 0.043), but this did not reach
      statistical significance using exact methods (OR 13.0, 95%CI 0.7-960.4, P =
      0.083). There were no significant effects for any secondary outcome.

PMID- 30218064
TI  - Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC)
      number in patients with bicuspid aortic valve with and without ascending aorta
      aneurysm.
AB  - Bicuspid aortic valve (BAV) is frequently associated with the development of
      ascending aortic aneurysm, even if the underlying mechanisms remain to be
      clarified. Here, we investigated if a deregulation of Notch1 signaling pathway
      and endothelial progenitor cells (EPCs) number is associated with BAV disease and
      an early ascending aortic aneurysm (AAA) onset. For this purpose, 70 subjects
      with BAV (M/F 50/20; mean age: 58.8 +/- 14.8 years) and 70 subjects with
      tricuspid aortic valve (TAV) (M/F 35/35; mean age: 69.1 +/- 12.8 years) and AAA
      complicated or not, were included. Interestingly, patients with AAA showed a
      significant increase in circulating Notch1 levels and EPC number than subjects
      without AAA. However, circulating Notch1 levels and EPC number were significantly
      lower in BAV subjects than TAV patients either in the presence or absence of AAA.
      Finally, Notch pathway was activated to a greater extent in aortic aneurysmatic
      portions with respect to healthy aortic fragments in both BAV and TAV patients.
      However, the expression of genes encoding components and ligands of Notch pathway
      in aortic tissues was significantly lower in BAV than TAV subjects. Our study
      demonstrates that BAV subjects are characterized by a significant decrease in
      both tissue and circulating levels of Notch pathway, and in blood EPC number than
      TAV patients, either in presence or absence of AAA disease.

PMID- 30218065
TI  - A facile synthesis of Au-nanoparticles decorated PbI2 single crystalline
      nanosheets for optoelectronic device applications.
AB  - This research communication presents a rapid and facile microwave-assisted
      synthesis of single crystalline nanosheets (SCNSs) of hexagonal lead iodide
      (PbI2) decorated with Au nanoparticles, a potential optoelectronics material.
      Homogeneous low dimensional AuNP decoration in PbI2 resulted in a new absorption
      band at ~604 nm and a shift in band gap from 3.23 to 3.00 eV. The significant
      enhancement of photoluminescent (PL) intensity observed in the AuNP-PbI2 SCNSs is
      attributed to the coupling of the localized surface plasmon resonanzce of AuNP
      leading to improved excitation and emission rates of PbI2-SCNSs in the region of
      the localized electromagnetic field. The Au-PbI2 SCNSs display a compelling
      increment in photoconductivity, and its fabricated photodetector showed a stable
      and switchable photo-response. Due to ease of synthesis and enhanced
      photoconductivity along with appealing PL features, Au-PbI2 SCNS has the
      potential to be used as a material of choice when fabricating an optoelectronic
      devices of high performance.

PMID- 30218066
TI  - Experimental and Computational Studies on the Basic Transmission Properties of
      Electromagnetic Waves in Softmaterial Waveguides.
AB  - Conventional waveguides are usually made of metallic materials, and they are
      effective pathways for the transmission of electromagnetic waves. A "Softmaterial
      waveguide", by contrast, is supposed to be made of dielectric material and ionic
      fluids. In this work, by means of both experiment and computational simulation we
      examined one kind of softmaterial waveguide, which has the configuration of ionic
      fluids filled in and out of a dielectric tube. We investigated configurations
      with varied parameters, i.e., tube thickness from 0.2 mm to 5.0 mm, tube length
      of 2.0-12.0 cm, ionic concentration covering 4 orders of magnitude from 0.0002
      2.0 mol/L, frequency of 10 Hz to 100 MHz for sine wave excitations, pulse
      duration of 5 ns to 100 ms for excitation pulses. We also mimicked the myelin
      sheath structure in myelinated axons in simulation. Both experimental and
      simulation results consistently showed a clear confinement effect for the energy
      flux of transmitting electromagnetic waves inside the dielectric tube, strongly
      supporting the model of softmaterail waveguide. The results revealed that the
      softmaterial waveguide had a low-pass nature, where the intensity of transmitted
      signals saturated at a duration of 10-100 MUs for pulses, or cut off at frequency
      of 10-100 kHz for sine waves. And, the transmission efficiency increased with the
      thickness of the dielectric layer, as well as ion concentration of the solution.
      The results may help for a better understanding various electrical communication
      behaviors observed in biosystems, where a natural lipid membrane with bilateral
      fluids was suggested as the efficient pathway for pulsed neural impulses in a way
      similar to soliton-like electromagnetic pulses transmitting in a softmaterial
      waveguide.

PMID- 30218067
TI  - Autophagy differentially regulates TNF receptor Fn14 by distinct mammalian Atg8
      proteins.
AB  - Autophagy, a conserved membrane trafficking process, sequesters cytoplasmic
      components into autophagosomes and targets them for lysosomal degradation. The
      TNF receptor Fn14 participates in multiple intracellular signaling pathways and
      is strongly induced upon tissue injury and solid tumorigenesis. While Fn14 is a
      short-lived protein, the regulation of its levels is largely obscure. Here we
      uncover a role for autophagy in Fn14 turnover, wherein specific core autophagy
      Atg8 proteins play distinct roles: Fn14 accumulates in the ERGIC in absence of
      GABARAP but within endosomes in the vicinity of autophagic membranes in absence
      of GATE-16. Moreover, GABARAP regulates overall cellular levels of Fn14, whereas
      GATE-16 regulates TWEAK signaling by Fn14 and thereby NF-kappaB activity. These
      findings not only implicate different Atg8 proteins in distinct roles within the
      mechanism of selective autophagic regulation of Fn14, but may also provide a more
      general view of their role in mediating autophagosome biogenesis from different
      membrane sources.

PMID- 30218068
TI  - Conditional and interaction gene-set analysis reveals novel functional pathways
      for blood pressure.
AB  - Gene-set analysis provides insight into which functional and biological
      properties of genes are aetiologically relevant for a particular phenotype. But
      genes have multiple properties, and these properties are often correlated across
      genes. This can cause confounding in a gene-set analysis, because one property
      may be statistically associated even if biologically irrelevant to the phenotype,
      by being correlated with gene properties that are relevant. To address this issue
      we present a novel conditional and interaction gene-set analysis approach, which
      attains considerable functional refinement of its conclusions compared to
      traditional gene-set analysis. We applied our approach to blood pressure
      phenotypes in the UK Biobank data (N = 360,243), the results of which we report
      here. We confirm and further refine several associations with multiple processes
      involved in heart and blood vessel formation but also identify novel
      interactions, among others with cardiovascular tissues involved in regulatory
      pathways of blood pressure homoeostasis.

PMID- 30218070
TI  - MAPK/ERK and JNK pathways regulate lipid synthesis and cell growth of
      Chlamydomonas reinhardtii under osmotic stress, respectively.
AB  - Microalgae have great potential for the production of biofuels due to the ability
      of the organism to accumulate large quantities of storage lipids under stress
      conditions. Mitogen activated protein kinase (MAPK) signaling cascades are widely
      recognized for their role in stress response signal transduction in eukaryotes.
      To assess the correlation between MAPK activation and lipid productivity,
      Chlamydomonas reinhardtii was studied under various concentrations of NaCl. The
      results demonstrated that C. reinhardtii exhibits elevated levels of
      extracellular-signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)
      activities after undergoing osmotic stress, as well as an increase in cellular
      lipid content. To establish a more direct causal link between both kinases and
      lipid productivity, C. reinhardtii was subjected to biochemically induced
      regulation of ERK and JNK pathways. Activating the MEK-ERK pathway via C6
      ceramide treatment increased ERK activation and lipid production simultaneously,
      while PD98059 mediated inhibition of the pathway yielded opposite results.
      Interestingly, suppression of the JNK pathway with SP600125 resulted in a
      substantial decrease in cell viability under osmotic stress. These results
      suggest that ERK and JNK MAP kinases have important roles in microalgal lipid
      accumulation and cell growth under osmotic stress, respectively.

PMID- 30218069
TI  - Catechol-O-methyltransferase (COMT) genotypes are associated with varying
      soluble, but not membrane-bound COMT protein in the human prefrontal cortex.
AB  - Catechol-O-methyltransferase (COMT) is an enzyme that catalyses the O
      methylation, and thereby the inactivation, of catechol-containing molecules. In
      humans, it has been suggested that COMT modulates cognitive ability, possibly by
      regulating degradation of dopamine in the prefrontal cortex. Hence, it is
      significant that two COMT SNPs, rs4680 (c.472 G > A, p.Val158Met) and rs4818
      (c.408 C > G), have been associated with cognitive ability in humans. We have
      shown these SNPs to be associated with levels of muscarinic M1 receptor mRNA in
      human cortex, which is significant as that receptor also regulates cognitive
      ability. We decided to determine if COMT genotype was associated with varying
      levels of COMT protein, as this could be a mechanism by which COMT genotype could
      be associated with changes in muscarinic M1 receptor mRNA levels. Hence, we
      measured COMT levels in prefrontal cortex obtained postmortem from 199 subjects,
      some of whom had a history of schizophrenia, major depressive disorders or
      bipolar disorders. Our data show, independent of diagnostic status, that genotype
      at rs4680 and rs4818, but not at rs737865 and rs165599, is associated with
      differing levels of soluble COMT (S-COMT), but not membrane-bound COMT (MB-COMT).
      These findings suggest that the association between COMT polymorphisms and
      cognitive functioning could be, at least in part, due to their association with
      varying levels of S-COMT. This is important as, unlike MB-COMT, the substrates
      targeted by S-COMT are likely to be intra-cellular rather than, like dopamine,
      located mainly in the synaptic vesicles or the extra-cellular space.

PMID- 30218071
TI  - Is the combinational administration of doxorubicin and glutathione a reasonable
      proposal?
AB  - The combinational administration of antioxidants and chemotherapeutic agents
      during conventional cancer treatment is among one of the most controversial areas
      in oncology. Although the data on the combinational usage of doxorubicin (DOX)
      and glutathione (GSH) agents have been explored for over 20 years, the duration,
      administration route, and authentic rationality have not yet been fully
      understood yet. In the current study, we systematically investigated the
      pharmacokinetics (PK) and pharmacodynamics (PD) with both in vivo and in vitro
      models to elucidate the influence of GSH on the toxicity and efficacy of DOX. We
      first studied the cardioprotective and hepatoprotective effects of GSH in Balb/c
      mice, H9c2, and HL7702 cells. We showed that coadministration of exogenous GSH
      (5, 50, and 500 mg/kg per day, intragastric) significantly attenuated DOX-induced
      cardiotoxicity and hepatotoxicity by increasing intracellular GSH levels, whereas
      the elevated GSH concentrations did not affect the exposure of DOX in mouse heart
      and liver. From PK and PD perspectives, then the influences of GSH on the
      chemotherapeutic efficacy of DOX were investigated in xenografted nude mice and
      cancer cell models, including MCF-7, HepG2, and Caco-2 cells, which revealed that
      administration of exogenous GSH dose-dependently attenuated the anticancer
      efficacy of DOX in vivo and in vitro, although the elevated GSH levels neither
      influenced the concentration of DOX in tumors in vivo, nor the uptake of DOX in
      MCF-7 tumor cells in vitro. Based on the results we suggest that the combined
      administration of GSH and DOX should be contraindicated during chemotherapy
      unless DOX has caused serious hepatotoxicity and cardiotoxicity.

PMID- 30218072
TI  - Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma
      cells in vitro and in vivo by activating AMPK signaling pathway.
AB  - Hispidulin (4',5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid isolated
      from the medicinal plant S. involucrata, which exhibits anti-neoplastic activity
      against several types of cancer. However, the mechanism underlying its anti
      cancer activity against hepatocellular carcinoma (HCC) has not been fully
      elucidated. In this study, we investigated whether and how hispidulin-induced
      apoptosis of human HCC cells in vitro and in vivo. We showed that hispidulin (10,
      20 MUmol/L) dose-dependently inhibited cell growth and promoted apoptosis through
      mitochondrial apoptosis pathway in human HCC SMMC7721 cells and Huh7 cells. More
      importantly, we revealed that its pro-apoptotic effects depended on endoplasmic
      reticulum stress (ERS) and unfolded protein response (UPR), as pretreatment with
      salubrinal, a selective ERS inhibitor, or shRNA targeting a UPR protein CHOP
      effectively abrogated hispidulin-induced cell apoptosis. Furthermore, we showed
      that hispidulin-induced apoptosis was mediated by activation of AMPK/mTOR
      signaling pathway as pretreatment with Compound C, an AMPK inhibitor, or AMPK
      targeting siRNA reversed the pro-apoptotic effect of hispidulin. In HCC xenograft
      nude mice, administration of hispidulin (25, 50 mg kg-1 d-1, ip, for 27 days)
      dose-dependently suppressed the tumor growth, accompanied by inducing ERS and
      apoptosis in tumor tissue. Taken together, our results demonstrate that
      hispidulin induces ERS-mediated apoptosis in HCC cells via activating the
      AMPK/mTOR pathway. This study provides new insights into the anti-tumor activity
      of hispidulin in HCC.

PMID- 30218073
TI  - Med23 serves as a gatekeeper of the myeloid potential of hematopoietic stem
      cells.
AB  - In response to myeloablative stresses, HSCs are rapidly activated to replenish
      myeloid progenitors, while maintaining full potential of self-renewal to ensure
      life-long hematopoiesis. However, the key factors that orchestrate HSC activities
      during physiological stresses remain largely unknown. Here we report that Med23
      controls the myeloid potential of activated HSCs. Ablation of Med23 in
      hematopoietic system leads to lymphocytopenia. Med23-deficient HSCs undergo
      myeloid-biased differentiation and lose the self-renewal capacity. Interestingly,
      Med23-deficient HSCs are much easier to be activated in response to physiological
      stresses. Mechanistically, Med23 plays essential roles in maintaining stemness
      genes expression and suppressing myeloid lineage genes expression. Med23 is
      downregulated in HSCs and Med23 deletion results in better survival under
      myeloablative stress. Altogether, our findings identify Med23 as a gatekeeper of
      myeloid potential of HSCs, thus providing unique insights into the relationship
      among Med23-mediated transcriptional regulations, the myeloid potential of HSCs
      and HSC activation upon stresses.

PMID- 30218075
TI  - New suspension-feeding radiodont suggests evolution of microplanktivory in
      Cambrian macronekton.
AB  - The rapid diversification of metazoans and their organisation in modern-style
      marine ecosystems during the Cambrian profoundly transformed the biosphere. What
      initially sparked this Cambrian explosion remains passionately debated, but the
      establishment of a coupling between pelagic and benthic realms, a key
      characteristic of modern-day oceans, might represent a primary ecological cause.
      By allowing the transfer of biomass and energy from the euphotic zone-the locus
      of primary production-to the sea floor, this biological pump would have boosted
      diversification within the emerging metazoan-dominated benthic communities.
      However, little is known about Cambrian pelagic organisms and their trophic
      interactions. Here we describe a filter-feeding Cambrian radiodont exhibiting
      morphological characters that likely enabled the capture of microplankton-sized
      particles, including large phytoplankton. This description of a large free
      swimming suspension-feeder potentially engaged in primary consumption suggests a
      more direct involvement of nekton in the establishment of an oceanic pelagic
      benthic coupling in the Cambrian.

PMID- 30218074
TI  - Extremely rare variants reveal patterns of germline mutation rate heterogeneity
      in humans.
AB  - A detailed understanding of the genome-wide variability of single-nucleotide
      germline mutation rates is essential to studying human genome evolution. Here, we
      use ~36 million singleton variants from 3560 whole-genome sequences to infer fine
      scale patterns of mutation rate heterogeneity. Mutability is jointly affected by
      adjacent nucleotide context and diverse genomic features of the surrounding
      region, including histone modifications, replication timing, and recombination
      rate, sometimes suggesting specific mutagenic mechanisms. Remarkably, GC content,
      DNase hypersensitivity, CpG islands, and H3K36 trimethylation are associated with
      both increased and decreased mutation rates depending on nucleotide context. We
      validate these estimated effects in an independent dataset of ~46,000 de novo
      mutations, and confirm our estimates are more accurate than previously published
      results based on ancestrally older variants without considering genomic features.
      Our results thus provide the most refined portrait to date of the factors
      contributing to genome-wide variability of the human germline mutation rate.

PMID- 30218076
TI  - Epidemiological tracing of Batrachochytrium salamandrivorans identifies
      widespread infection and associated mortalities in private amphibian collections.
AB  - The amphibian chytrid fungus Batrachochytrium salamandrivorans (Bsal) infects
      newts and salamanders (urodele amphibians), in which it can cause fatal disease.
      This pathogen has caused dramatic fire salamander population declines in Belgium,
      the Netherlands and Germany since its discovery in 2010. Thought to be native to
      Asia, it has been hypothesised that Bsal was introduced to Europe with the
      importation of infected amphibians for the commercial pet trade. Following the
      discovery of Bsal in captive amphibians in the United Kingdom in 2015, we used
      contact-tracing to identify epidemiologically-linked private amphibian
      collections in Western Europe. Of 16 linked collections identified, animals were
      tested from 11 and urodeles tested positive for Bsal in seven, including the
      identification of the pathogen in Spain for the first time. Mortality of Bsal
      positive individuals was observed in five collections. Our results indicate that
      Bsal is likely widespread within the private amphibian trade, at least in Europe.
      These findings are important for informing policy regarding Bsal control
      strategies.

PMID- 30218077
TI  - Spatially dependent atom-photon entanglement.
AB  - The atom-photon entanglement using the Laguerre-Gaussian (LG) beams is studied in
      the closed-loop three-level V-type quantum systems. We consider two schemes with
      near-degenerate and non-degenerate upper levels: in the first, the effect of the
      quantum interference due to the spontaneous emission is taken into account and in
      the second, a microwave plane wave is applied to the upper levels transition. It
      is shown that the atom-photon entanglement in both schemes depends on the
      intensity profile as well as the orbital angular momentum (OAM) of the applied
      fields so that the various spatially dependent entanglement patterns can be
      generated by Laguerre-Gaussian beams with different OAMs. However, due to the
      zero intensity,no entanglement appears in the center of the optical vortex beams.
      As a result, the entanglement between dressed atom and its spontaneous emissions
      in different points of the atomic vapor cell can be controlled by the OAM of the
      applied fields. Moreover, our numerical results show that the number of the local
      maximum degree of entanglement (DEM) peaks depends on the OAM of the applied
      fields. The degrees of freedom for OAM play a crucial role in spatially dependent
      atom-photon entanglement in such a way that it may possess broad applications in
      high-dimensional quantum information processing and data storage.

PMID- 30218078
TI  - Assortative mixing in spatially-extended networks.
AB  - We focus on spatially-extended networks during their transition from short-range
      connectivities to a scale-free structure expressed by heavy-tailed degree
      distribution. In particular, a model is introduced for the generation of such
      graphs, which combines spatial growth and preferential attachment. In this model
      the transition to heterogeneous structures is always accompanied by a change in
      the graph's degree-degree correlation properties: while high assortativity levels
      characterize the dominance of short distance couplings, long-range connectivity
      structures are associated with small amounts of disassortativity. Our results
      allow to infer that a disassortative mixing is essential for establishing long
      range links. We discuss also how our findings are consistent with recent
      experimental studies of 2-dimensional neuronal cultures.

PMID- 30218079
TI  - Integrative analysis of differentially expressed genes and miRNAs predicts
      complex T3-mediated protective circuits in a rat model of cardiac ischemia
      reperfusion.
AB  - Thyroid hormone (T3) dyshomeostasis in the cardiac ischemia-reperfusion (IR)
      setting negatively impacts on mitochondria function and extracellular matrix
      remodeling. The modulation of cardiac miRNAs may represent the underlying
      molecular mechanisms, but a systems biology perspective investigating this
      critical issue in depth is still lacking. A rat model of myocardial IR, with or
      without an early short-term T3-replacement, was used to predict putative T3
      dependent miRNA-gene interactions targeted to mitochondria quality control and
      wound healing repair. As evidenced by mRNA and miRNA expression profiling, the T3
      supplementation reverted the expression of 87 genes and 11 miRNAs that were
      dysregulated in the untreated group. In silico crossing and functional analysis
      of the T3-associated differentially expressed transcripts, identified a signature
      of interconnected miRNA-gene regulatory circuits that confer resistance to
      noxious cascades of acute stress. In this network the T3-down-regulated Tp53, Jun
      and Sp1 transcription factors emerge as critical nodes linking intrinsic cell
      death and oxidative stress pathways to adverse remodeling cascades. The data
      presented here provide a novel insight into the molecular basis of T3
      cardioprotection in the early post-IR phase and highlight the contribution of a
      previously unappreciated complex T3-regulatory network that may be helpful in
      translating T3 replacement into clinical practice.

PMID- 30218080
TI  - Chromatin swelling drives neutrophil extracellular trap release.
AB  - Neutrophilic granulocytes are able to release their own DNA as neutrophil
      extracellular traps (NETs) to capture and eliminate pathogens. DNA expulsion
      (NETosis) has also been documented for other cells and organisms, thus
      highlighting the evolutionary conservation of this process. Moreover,
      dysregulated NETosis has been implicated in many diseases, including cancer and
      inflammatory disorders. During NETosis, neutrophils undergo dynamic and dramatic
      alterations of their cellular as well as sub-cellular morphology whose
      biophysical basis is poorly understood. Here we investigate NETosis in real-time
      on the single-cell level using fluorescence and atomic force microscopy. Our
      results show that NETosis is highly organized into three distinct phases with a
      clear point of no return defined by chromatin status. Entropic chromatin swelling
      is the major physical driving force that causes cell morphology changes and the
      rupture of both nuclear envelope and plasma membrane. Through its material
      properties, chromatin thus directly orchestrates this complex biological process.

PMID- 30218081
TI  - High-throughput sequencing revealed that microRNAs were involved in the
      development of superior and inferior grains in bread wheat.
AB  - High-throughput sequencing was employed to investigate the expression of miRNAs
      and their target genes in superior and inferior seeds of Aikang 58. Small RNA
      sequencing revealed 620 conserved and 64 novel miRNAs in superior grains, and 623
      conserved and 66 novel miRNAs in inferior grains. Among these, 97 known miRNAs,
      and eight novel miRNAs showed differential expression between the superior and
      inferior seeds. Degradome sequencing revealed at least 140 candidate target genes
      associated with 35 miRNA families during the development of superior and inferior
      seeds. GO and KEGG pathway analysis showed that the differentially expressed
      miRNAs, both conserved and novel, were likely involved in hormone production,
      carbohydrate metabolic pathways, and cell division. We validated eight known and
      four novel grain development-related miRNAs and their target genes by
      quantitative real-time polymerase chain reaction to ensure the reliability of
      small RNA and degradome-seq results. Of these, miR160 and miR165/166 were knocked
      down in Arabidopsis using short-tandem target mimic (STTM160 and STTM165/166)
      technology, which confirmed their roles in seed development. Specifically,
      STTM160 showed significantly smaller grain size, lower grain weight, shorter
      siliques length, shorter plant height, and more serrated leaves, whereas
      STTM165/166 showed decreased seed number, disabled siliques, and curled upward
      leaves.

PMID- 30218082
TI  - A self-improving triboelectric nanogenerator with improved charge density and
      increased charge accumulation speed.
AB  - Charge density is one of the most important parameters of triboelectric
      nanogenerators since it directly determines performance; unfortunately, it is
      largely restricted by the phenomenon of air breakdown. Here, we design a self
      improving triboelectric nanogenerator with improved charge density. A maximum
      effective charge density of 490 MUC m-2 is obtained, which is about two times
      higher than the highest reported charge density of a triboelectric nanogenerator
      that operates in an air environment. At the beginning of the working process, the
      charge accumulation speed is increased 5.8 times in comparison with a
      triboelectric nanogenerator that is incorporated into the self-improving device.
      The self-improving triboelectric nanogenerator overcomes the restriction of air
      breakdown and exhibits an increased effective charge density, which contributes
      to the improvement of the output performance, and the increase of charge
      accumulation speed will accelerate the increase of the output power at the start
      of operation.

PMID- 30218084
TI  - Major Depression Impairs the Use of Reward Values for Decision-Making.
AB  - Depression is a debilitating condition with a high prevalence. Depressed patients
      have been shown to be diminished in their ability to integrate their
      reinforcement history to adjust future behaviour during instrumental reward
      learning tasks. Here, we tested whether such impairments could also be observed
      in a Pavlovian conditioning task. We recruited and analysed 32 subjects, 15 with
      depression and 17 healthy controls, to study behavioural group differences in
      learning and decision-making. Participants had to estimate the probability of
      some fractal stimuli to be associated with a binary reward, based on a few
      passive observations. They then had to make a choice between one of the observed
      fractals and another target for which the reward probability was explicitly
      given. Computational modelling was used to succinctly describe participants'
      behaviour. Patients performed worse than controls at the task. Computational
      modelling revealed that this was caused by behavioural impairments during both
      learning and decision phases. Depressed subjects showed lower memory of observed
      rewards and had an impaired ability to use internal value estimations to guide
      decision-making in our task.

PMID- 30218085
TI  - Contribution of protein Gar1 to the RNA-guided and RNA-independent rRNA:Psi
      synthase activities of the archaeal Cbf5 protein.
AB  - Archaeal RNA:pseudouridine-synthase (PUS) Cbf5 in complex with proteins L7Ae,
      Nop10 and Gar1, and guide box H/ACA sRNAs forms ribonucleoprotein (RNP) catalysts
      that insure the conversion of uridines into pseudouridines (Psis) in ribosomal
      RNAs (rRNAs). Nonetheless, in the absence of guide RNA, Cbf5 catalyzes the in
      vitro formation of Psi2603 in Pyrococcus abyssi 23S rRNA and of Psi55 in tRNAs.
      Using gene-disrupted strains of the hyperthermophilic archaeon Thermococcus
      kodakarensis, we studied the in vivo contribution of proteins Nop10 and Gar1 to
      the dual RNA guide-dependent and RNA-independent activities of Cbf5 on 23S rRNA.
      The single-null mutants of the cbf5, nop10, and gar1 genes are viable, but
      display a thermosensitive slow growth phenotype. We also generated a single-null
      mutant of the gene encoding Pus10, which has redundant activity with Cbf5 for in
      vitro formation of Psi55 in tRNA. Analysis of the presence of Psis within the
      rRNA peptidyl transferase center (PTC) of the mutants demonstrated that Cbf5 but
      not Pus10 is required for rRNA modification. Our data reveal that, in contrast to
      Nop10, Gar1 is crucial for in vivo and in vitro RNA guide-independent formation
      of Psi2607 (Psi2603 in P. abyssi) by Cbf5. Furthermore, our data indicate that
      pseudouridylation at orphan position 2589 (2585 in P. abyssi), for which no PUS
      or guide sRNA has been identified so far, relies on RNA- and Gar1-dependent
      activity of Cbf5.

PMID- 30218087
TI  - Early identification of esophageal squamous neoplasm by hyperspectral endoscopic
      imaging.
AB  - Esophageal squamous neoplasm presents a spectrum of different diatheses. A
      precise assessment for individualized treatment depends on the accuracy of the
      initial diagnosis. Detection relies on comprehensive and accurate white-light,
      iodine staining, and narrow-band imaging endoscopy. These methods have
      limitations in addition to its invasive nature and the potential risks related to
      the method. These limitations include difficulties in precise tumor delineation
      to enable complete resection, inflammation and malignancy differentiation, and
      stage determination. The resolution of these problems depends on the surgeon's
      ability and experience with available technology for visualization and resection.
      We proposed a method for identifying early esophageal cancerous lesion by
      endoscopy and hyperspectral endoscopic imaging. Experimental result shows the
      characteristic spectrum of a normal esophagus, precancerous lesion, canceration,
      and intraepithelial papillary capillary loop can be identified through principal
      component score chart. The narrow-band imaging (NBI) image shows remarkable
      spectral characteristic distribution, and the sensitivity and specificity of the
      proposed method are higher than those of other methods by ~0.8 and ~0.88,
      respectively. The proposed method enables the accurate visualization of target
      organs, it may be useful to capsule endoscope and telemedicine, which requires
      highly precise images for diagnosis.

PMID- 30218086
TI  - Transgenic zebrafish model for quantification and visualization of tissue
      toxicity caused by alloying elements in newly developed biodegradable metal.
AB  - The cytotoxicity of alloying elements in newly developed biodegradable metals can
      be assessed through relatively low-cost and rapid in vitro studies using
      different cell types. However, such approaches have limitations; as such,
      additional investigations in small mammalian models are required that
      recapitulate the physiological environment. In this study, we established a
      zebrafish (Danio rerio) model for cytotoxicity evaluations that combines the
      physiological aspects of an animal model with the speed and simplicity of a cell
      based assay. The model was used to assess the cytotoxicity of five common
      alloying elements in biodegradable implant materials. Conventional in vitro
      testing using heart, liver, and endothelial cell lines performed in parallel with
      zebrafish studies revealed statistically significant differences in toxicity (up
      to 100-fold), along with distinct changes in the morphology of the heart, liver,
      and blood vessels that were undetectable in cell cultures. These results indicate
      that our zebrafish model is a useful alternative to mammalian systems for
      accurately and rapidly evaluating the in vivo toxicity of newly developed
      metallic materials.

PMID- 30218083
TI  - Characteristic patterns of inter- and intra-hemispheric metabolic connectivity in
      patients with stable and progressive mild cognitive impairment and Alzheimer's
      disease.
AB  - The change in hypometabolism affects the regional links in the brain network.
      Here, to understand the underlying brain metabolic network deficits during the
      early stage and disease evolution of AD (Alzheimer disease), we applied
      correlation analysis to identify the metabolic connectivity patterns using 18F
      FDG PET data for NC (normal control), sMCI (stable MCI), pMCI (progressive MCI)
      and AD, and explore the inter- and intra-hemispheric connectivity between
      anatomically-defined brain regions. Regions extracted from 90 anatomical
      structures were used to construct the matrix for measuring the inter- and intra
      hemispheric connectivity. The brain connectivity patterns from the metabolic
      network show a decreasing trend of inter- and intra-hemispheric connections for
      NC, sMCI, pMCI and AD. Connection of temporal to the frontal or occipital regions
      is a characteristic pattern for conversion of NC to MCI, and the density of links
      in the parietal-occipital network is a differential pattern between sMCI and
      pMCI. The reduction pattern of inter and intra-hemispheric brain connectivity in
      the metabolic network depends on the disease stages, and is with a decreasing
      trend with respect to disease severity. Both frontal-occipital and parietal
      occipital connectivity patterns in the metabolic network using 18F-FDG PET are
      the key feature for differentiating disease groups in AD.

PMID- 30218088
TI  - Enhanced uptake of gH625 by blood brain barrier compared to liver in vivo:
      characterization of the mechanism by an in vitro model and implications for
      delivery.
AB  - We have investigated the crossing of the blood brain barrier (BBB) by the peptide
      gH625 and compared to the uptake by liver in vivo. We clearly observed that in
      vivo administration of gH625 allows the crossing of the BBB, although part of the
      peptide is sequestered by the liver. Furthermore, we used a combination of
      biophysical techniques to gain insight into the mechanism of interaction with
      model membranes mimicking the BBB and the liver. We observed a stronger
      interaction for membranes mimicking the BBB where gH625 clearly undergoes a
      change in secondary structure, indicating the key role of the structural change
      in the uptake mechanism. We report model studies on liposomes which can be
      exploited for the optimization of delivery tools.

PMID- 30218089
TI  - Summertime Primary and Secondary Contributions to Southern Ocean Cloud
      Condensation Nuclei.
AB  - Atmospheric aerosols in clean remote oceanic regions contribute significantly to
      the global albedo through the formation of haze and cloud layers; however, the
      relative importance of 'primary' wind-produced sea-spray over secondary (gas-to
      particle conversion) sulphate in forming marine clouds remains unclear. Here we
      report on marine aerosols (PM1) over the Southern Ocean around Antarctica, in
      terms of their physical, chemical, and cloud droplet activation properties. Two
      predominant pristine air masses and aerosol populations were encountered:
      modified continental Antarctic (cAA) comprising predominantly sulphate with
      minimal sea-salt contribution and maritime Polar (mP) comprising sulphate plus
      sea-salt. We estimate that in cAA air, 75% of the CCN are activated into cloud
      droplets while in mP air, 37% are activated into droplets, for corresponding peak
      supersaturation ranges of 0.37-0.45% and 0.19-0.31%, respectively. When realistic
      marine boundary layer cloud supersaturations are considered (e.g. ~0.2-0.3%), sea
      salt CCN contributed 2-13% of the activated nuclei in the cAA air and 8-51% for
      the marine air for surface-level wind speed < 16 m s-1. At higher wind speeds,
      primary marine aerosol can even contribute up to 100% of the activated CCN, for
      corresponding peak supersaturations as high as 0.32%.

PMID- 30218090
TI  - The m6A-methylase complex recruits TREX and regulates mRNA export.
AB  - N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic
      mRNA. This modification has previously been shown to alter the export kinetics
      for mRNAs though the molecular details surrounding this phenomenon remain poorly
      understood. Recruitment of the TREX mRNA export complex to mRNA is driven by
      transcription, 5' capping and pre-mRNA splicing. Here we identify a fourth
      mechanism in human cells driving the association of TREX with mRNA involving the
      m6A methylase complex. We show that the m6A complex recruits TREX to m6A modified
      mRNAs and this process is essential for their efficient export. TREX also
      stimulates recruitment of the m6A reader protein YTHDC1 to the mRNA and the m6A
      complex influences the interaction of TREX with YTHDC1. Together our studies
      reveal a key role for TREX in the export of m6A modified mRNAs.

PMID- 30218091
TI  - Using a Classifier Fusion Strategy to Identify Anti-angiogenic Peptides.
AB  - Anti-angiogenic peptides perform distinct physiological functions and potential
      therapies for angiogenesis-related diseases. Accurate identification of anti
      angiogenic peptides may provide significant clues to understand the essential
      angiogenic homeostasis within tissues and develop antineoplastic therapies. In
      this study, an ensemble predictor is proposed for anti-angiogenic peptide
      prediction by fusing an individual classifier with the best sensitivity and
      another individual one with the best specificity. We investigate predictive
      capabilities of various feature spaces with respect to the corresponding optimal
      individual classifiers and ensemble classifiers. The accuracy and Matthew's
      Correlation Coefficient (MCC) of the ensemble classifier trained by Bi-profile
      Bayes (BpB) features are 0.822 and 0.649, respectively, which represents the
      highest prediction results among the investigated prediction models.
      Discriminative features are obtained from BpB using the Relief algorithm followed
      by the Incremental Feature Selection (IFS) method. The sensitivity, specificity,
      accuracy, and MCC of the ensemble classifier trained by the discriminative
      features reach up to 0.776, 0.888, 0.832, and 0.668, respectively. Experimental
      results indicate that the proposed method is far superior to the previous study
      for anti-angiogenic peptide prediction.

PMID- 30218092
TI  - The differences in bioaccumulation and effects between Se(IV) and Se(VI) in the
      topmouth gudgeon Pseudorasbora parva.
AB  - Selenium (Se) might be protective against oxidative stress at nutritional levels,
      but elevated Se concentrations in the diet has been revealed as the main culprit
      for the extinction of natural fish populations in Se-contaminated lakes. Though
      Se predominate as waterborne selenite (IV) and selenate (VI) in the water, the
      differences in bioaccumulation, effects (e.g., oxidative stress, antioxidants
      etc.) and molecular mechanisms between Se(IV) and Se(VI) have been relatively
      understudied in wild fish. In this study, the P. parva were exposed to waterborne
      Se (10, 200 and 1000 MUg/L of Se(IV) or Se(VI)) and sampled at 4, 14 and 28 days.
      Bioaccumulation, tissue distributions of Se and following effects in different
      tissues were evaluated. The results showed that the levels of Se in the gills and
      intestine were significantly elevated with a seemingly concentration-dependent
      pattern in the Se(IV) treatment, with respectively 173.3% and 57.2% increase
      after 28 days of exposure, relative to that of Se(VI) treatment. Additionally,
      significant accumulation of Se was also observed in the muscle of Se(IV) treated
      fish. Se exposure increased the MDA levels in the brain and gills in the Se(IV)
      treatment, but less apparent in the Se(VI) treatment. Meanwhile, Se exposure
      lowered (at least 56%) the activity of GST in the gills, but increased the
      activity of AChE in the muscle (~69%) and brain (~50%) after 28 d. Most
      importantly, after 28 d of exposure, Se exposure caused significant decrease in
      GSH levels in the gills (at least 35%) and in all tissues examined at the highest
      test concentration. In general, the results showed that Se(IV) led to faster
      accumulation of Se than Se(VI) in P. parva, and the resulted lipid peroxidation
      was closely related to the levels of antioxidants, especially GSH. Our results
      suggest that the ecotoxicological effects of waterborne selenite and selenate
      differ in this freshwater species in the field.

PMID- 30218093
TI  - Association of Percentage Body Fat and Metabolic Health in Offspring of Patients
      with Cardiovascular Diseases.
AB  - Family history was one of the major risk factors for developing adverse health
      outcomes such as metabolic syndrome (MetS), type 2 diabetes mellitus (DM) and
      hypertension (HTN). Our aim was to examine the relationship between different
      family histories and cardiometabolic events, including DM, stroke, myocardial
      infarction (MI), and HTN. Participants who attended the health examinations at
      the Tri-Service General Hospital from 2010 to 2016 were enrolled in the study and
      were categorized into four groups by representing different family history. A
      multivariable logistic regression model was used for the associations between
      various family history with the cardiometabolic events. Subjects with family
      history of DM were divided into quartiles by percentage body fat (PBF) to be
      analyzed for these adverse outcomes. In the cross-sectional analysis, subjects
      with family history of DM had significant association with MetS (OR = 1.34
      [95%CI: 1.17-1.54]) and DM (OR = 3.03 [95%CI: 2.44-3.76]), and those with family
      history of HTN were positively associated with HTN (OR = 1.60 [95%CI: 1.41
      1.81]). Notably, those with family history of DM in higher PBF quartiles had
      substantially increased association of cardiometabolic events (MetS: OR = 15.20
      [95%CI: 9.87-23.39]; DM: OR = 3.35 [95%CI: 1.91-5.90]; HTN: 2.81 [95%CI: 1.84
      4.29]). Individuals with family history of DM were positively associated with
      MetS and DM, and those with family history of HTN was associated with HTN. Family
      history assessment was requested especially in obese population for screening
      adverse health outcomes.

PMID- 30218094
TI  - A leaky voltage sensor domain of cardiac sodium channels causes arrhythmias
      associated with dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a structural heart disease that causes dilatation
      of cardiac chambers and impairs cardiac contractility. The SCN5A gene encodes
      Nav1.5, the predominant cardiac sodium channel alpha subunit. SCN5A mutations
      have been identified in patients with arrhythmic disorders associated with DCM.
      The characterization of Nav1.5 mutations located in the voltage sensor domain
      (VSD) and associated with DCM revealed divergent biophysical defects that do not
      fully explain the pathologies observed in these patients. The purpose of this
      study was to characterize the pathological consequences of a gating pore in the
      heart arising from the Nav1.5/R219H mutation in a patient with complex cardiac
      arrhythmias and DCM. We report its properties using cardiomyocytes derived from
      patient-specific human induced pluripotent stem cells. We showed that this
      mutation generates a proton leak (called gating pore current). We also described
      disrupted ionic homeostasis, altered cellular morphology, electrical properties,
      and contractile function, most probably linked to the proton leak. We thus
      propose a novel link between SCN5A mutation and the complex pathogenesis of
      cardiac arrhythmias and DCM. Furthermore, we suggest that leaky channels would
      constitute a common pathological mechanism underlying several neuronal,
      neuromuscular, and cardiac pathologies.

PMID- 30218096
TI  - Reassessing Impacts of Extended Daily Exposure to Low Level Solar UV Radiation.
AB  - Currently, health agencies recommend that no sun-protection is required when the
      UV Index (UVI) is less than 3. We use high-quality data from spectroradiometers
      and model calculations to demonstrate that this simplification is seriously
      flawed, particularly for mid-latitude conditions. For days when the peak UVI is
      below the threshold for advising protection, the daily dose of sun-burning UV
      available frequently far exceeds the threshold for damage to fair skin. This may
      have important health consequences, as populations at mid latitudes include a
      significant proportion with fair skin that is susceptible to damage.

PMID- 30218095
TI  - Preparation of quantum information encoded on three-photon decoherence-free
      states via cross-Kerr nonlinearities.
AB  - We present a scheme to encode quantum information (single logical qubit
      information) into three-photon decoherence-free states, which can conserve
      quantum information from collective decoherence, via nonlinearly optical gates
      (using cross-Kerr nonlinearities: XKNLs) and linearly optical devices. For the
      preparation of the decoherence-free state, the nonlinearly optical gates (multi
      photon gates) consist of weak XKNLs, quantum bus (qubus) beams, and photon-number
      resolving (PNR) measurement. Then, by using a linearly optical device, quantum
      information can be encoded on three-photon decoherence-free state prepared.
      Subsequently, by our analysis, we show that the nonlinearly optical gates using
      XKNLs, qubus beams, and PNR measurement are robust against the decoherence effect
      (photon loss and dephasing) in optical fibers. Consequently, our scheme can be
      experimentally implemented to efficiently generate three-photon decoherence-free
      state encoded quantum information, in practice.

PMID- 30218097
TI  - Meta-analysis of genome-wide association studies of aggressive and chronic
      periodontitis identifies two novel risk loci.
AB  - Periodontitis is one of the most common inflammatory diseases, with a prevalence
      of 11% worldwide for the severe forms and an estimated heritability of 50%. It is
      classified into the widespread moderate form chronic periodontitis (CP) and the
      rare early-onset and severe phenotype aggressive periodontitis (AgP). These
      different disease manifestations are thought to share risk alleles and
      predisposing environmental factors. To obtain novel insights into the shared
      genetic etiology and the underlying molecular mechanisms of both forms, we
      performed a two step-wise meta-analysis approach using genome-wide association
      studies of both phenotypes. Genotypes from imputed genome-wide association
      studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North
      West European genetic background were included. Two loci were associated with
      periodontitis at a genome-wide significance level. They located within the
      pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 * 10-9, OR = 1.36, 95%
      CI = [1.23-1.51]) and intronic of the long intergenic non-coding RNA LOC107984137
      on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 * 10-9, OR
      = 1.24, 95% CI = [1.15-1.34]). This study identified novel risk loci of
      periodontitis, adding to the genetic basis of AgP and CP.

PMID- 30218098
TI  - Search for cis-acting factors and maternal effect variants in Silver-Russell
      patients with ICR1 hypomethylation and their mothers.
AB  - Silver-Russell syndrome is an imprinting disorder characterized by severe
      intrauterine and postnatal growth retardation. The majority of patients show loss
      of methylation (LOM) of the H19/IGF2 IG-DMR (ICR1) in 11p15.5. In ~10% of these
      patients aberrant methylation of additional imprinted loci on other chromosomes
      than 11 can be observed (multilocus imprinting defect - MLID). Recently, genomic
      variations in the ICR1 have been associated with disturbed methylation of the
      ICR1. In addition, variants in factors contributing to the life cycle of
      imprinting are discussed to cause aberrant imprinting, including MLID. These
      variants can either be identified in the patients with imprinting disorders
      themselves or in their mothers. We performed comprehensive studies to elucidate
      the role of both cis-acting variants in 11p15.5 as well as of maternal effect
      variants in the etiology of ICR1 LOM. Whereas copy number analysis and next
      generation sequencing in the ICR1 did not provide any evidence for a variant,
      search for maternal effect variants in 21 mothers of patients with ICR1 LOM
      identified two carriers of NLRP5 variants. By considering our results as well as
      those from the literature, we conclude that the causes for epimutations are
      heterogeneous. MLID might be regarded as an own etiological subgroup, associated
      with maternal effect variants in NLRP and functionally related genes. In
      addition, these variants might also contribute to LOM of single imprinted loci.
      Furthermore, genomic variants in the patients themselves might result in aberrant
      methylation patterns and need further investigation.

PMID- 30218099
TI  - Imaging of human cells exposed to an antifungal antibiotic amphotericin B reveals
      the mechanisms associated with the drug toxicity and cell defence.
AB  - Amphotericin B is an antibiotic used in pharmacotherapy of life-threatening
      mycotic infections. Unfortunately, the applicability of this antibiotic is
      associated with highly toxic side effects. In order to understand molecular
      mechanisms underlying toxicity of amphotericin B to patients, two cell lines,
      human normal colon epithelial cells (CCD 841 CoTr) and human colon adenocarcinoma
      cells (HT-29) were cultured in the presence of the drug and imaged with the
      application of fluorescence lifetime imaging microscopy and Raman scattering
      microscopy. The results of the cell viability assays confirm high toxicity of
      amphotericin B towards human cells. The images recorded demonstrate effective
      binding of amphotericin B to biomembranes. Analysis of the images reveals the
      operation of a defence mechanism based upon the elimination of molecules of the
      drug from living cells via formation of small amphotericin B-containing lipid
      vesicles. The fact that exosomes formed are devoid of cholesterol, as concluded
      on the basis of the results of Raman analysis, suggests that sequestration of
      sterols from the lipid phase of biomembranes is not a sole mechanism responsible
      for the toxic side effects of amphotericin B. Alternatively, the results imply
      that molecules of the drug present directly within the hydrophobic membrane core
      disturb the lipid membrane structure and affect their biological functions.

PMID- 30218100
TI  - An experimental murine model to study periodontitis.
AB  - Periodontal disease (PD) is a common dental disease associated with the
      interaction between dysbiotic oral microbiota and host immunity. It is a
      prevalent disease, resulting in loss of gingival tissue, periodontal ligament,
      cementum and alveolar bone. PD is a major form of tooth loss in the adult
      population. Experimental animal models have enabled the study of PD pathogenesis
      and are used to test new therapeutic approaches for treating the disease. The
      ligature-induced periodontitis model has several advantages as compared with
      other models, including rapid disease induction, predictable bone loss and the
      capacity to study periodontal tissue and alveolar bone regeneration because the
      model is established within the periodontal apparatus. Although mice are the most
      convenient and versatile animal models used in research, ligature-induced
      periodontitis has been more frequently used in large animals. This is mostly due
      to the technical challenges involved in consistently placing ligatures around
      murine teeth. To reduce the technical challenge associated with the traditional
      ligature model, we previously developed a simplified method to easily install a
      bacterially retentive ligature between two molars for inducing periodontitis. In
      this protocol, we provide detailed instructions for placement of the ligature and
      demonstrate how the model can be used to evaluate gingival tissue inflammation
      and alveolar bone loss over a period of 18 d after ligature placement. This model
      can also be used on germ-free mice to investigate the role of human oral bacteria
      in periodontitis in vivo. In conclusion, this protocol enables the mechanistic
      study of the pathogenesis of periodontitis in vivo.

PMID- 30218101
TI  - Single-mRNA detection in living S. cerevisiae using a re-engineered MS2 system.
AB  - The MS2 system has been widely used, in organisms ranging from bacteria to higher
      eukaryotes, to image single mRNAs in intact cells with high precision. We have
      recently re-engineered the MS2 system for accurate detection of mRNAs in living
      Saccharomyces cerevisiae. Previous MS2 systems affected the degradation of the
      tagged mRNA, which led to accumulation of MS2 fragments and to erroneous
      conclusions about mRNA localization and expression. Here we describe a step-by
      step protocol for the use of our latest MS2 system (MBSV6) for detecting
      endogenously tagged mRNAs using wide-field fluorescent microscopy in living
      yeast. The procedure is divided into three stages: tagging of endogenous gene
      with MBSV6 (~2 weeks), a two-color single-molecule RNA fluorescent in situ
      hybridization (smFISH) procedure to quantitatively assess whether mRNAs tagged
      with MS2 and MS2-coat protein (MCP) behave like untagged mRNAs (2 d, plus
      additional time for quantification), and a procedure to quantify single mRNAs by
      live imaging using wide-field microscopy (1 d, plus additional time for
      quantification). With this method it is now possible to interrogate all phases of
      mRNA expression, from transcription through decay. The described protocol is
      designed for S. cerevisiae; however, we think that our approach and the
      considerations discussed here can be extended to Escherichia coli, Drosophila,
      Caenorhabditis elegans, and mammalian cells.

PMID- 30218102
TI  - Mapping heterogeneity of cellular mechanics by multi-harmonic atomic force
      microscopy.
AB  - The goal of mechanobiology is to understand the links between changes in the
      physical properties of living cells and normal physiology and disease. This
      requires mechanical measurements that have appropriate spatial and temporal
      resolution within a single cell. Conventional atomic force microscopy (AFM)
      methods that acquire force curves pointwise are used to map the heterogeneous
      mechanical properties of cells. However, the resulting map acquisition time is
      much longer than that required to study many dynamic cellular processes. Dynamic
      AFM (dAFM) methods using resonant microcantilevers are compatible with higher
      speed, high-resolution scanning; however, they do not directly acquire force
      curves and they require the conversion of a limited number of instrument
      observables to local mechanical property maps. We have recently developed a
      technique that allows commercial AFM systems equipped with direct cantilever
      excitation to quantitatively map the viscoelastic properties of live cells. The
      properties can be obtained at several widely spaced frequencies with nanometer
      range spatial resolution and with fast image acquisition times (tens of seconds).
      Here, we describe detailed procedures for quantitative mapping, including sample
      preparation, AFM calibration, and data analysis. The protocol can be applied to
      different biological samples, including cells and viruses. The transition from
      dAFM imaging to quantitative mapping should be easily achievable for experienced
      AFM users, who will be able to set up the protocol in <30 min.

PMID- 30218103
TI  - The sense of agency shapes body schema and peripersonal space.
AB  - Body schema, a sensorimotor representation of the body used for planning and
      executing movements, is plastic because it extends by using a tool to reach far
      objects. Modifications of peripersonal space, i.e., a functional representation
      of reach space, usually co-occur with body schema changes. Here, we hypothesized
      that such plastic changes depend on the experience of controlling the course of
      events in space trough one's own actions, i.e., the sense of agency. In two
      experiments, body schema and peripersonal space were assessed before and after
      the participants' sense of agency over a virtual hand was manipulated. Body
      schema and peripersonal space enlarged or contracted depending on whether the
      virtual hand was presented in far space, or closer to the participants' body than
      the real hand. These findings suggest that body schema and peripersonal space are
      affected by the dynamic mapping between intentional body movements and expected
      consequences in space.

PMID- 30218104
TI  - Publisher Correction: Concerns with yeast mitochondrial ADP/ATP carrier's
      integrity in DPC.
AB  - In the version of this article originally published, references 6 and 7 were
      interchanged in the reference list. The error has been corrected in the HTML and
      PDF versions of the article.

PMID- 30218105
TI  - CD69 prevents PLZFhi innate precursors from prematurely exiting the thymus and
      aborting NKT2 cell differentiation.
AB  - While CD69 may regulate thymocyte egress by inhibiting S1P1 expression, CD69
      expression is not thought to be required for normal thymocyte development. Here
      we show that CD69 is in fact specifically required for the differentiation of
      mature NKT2 cells, which do not themselves express CD69. Mechanistically, CD69
      expression is required on CD24+ PLZFhi innate precursors for their retention in
      the thymus and completion of their differentiation into mature NKT2 cells. By
      contrast, CD69-deficient CD24+ PLZFhi innate precursors express S1P1 and
      prematurely exit the thymus, while S1P1 inhibitor treatment of CD69-deficient
      mice retains CD24+ PLZFhi innate precursors in the thymus and restores NKT2 cell
      differentiation. Thus, CD69 prevents S1P1 expression on CD24+ PLZFhi innate
      precursor cells from aborting NKT2 differentiation in the thymus. This study
      reveals the importance of CD69 to prolong the thymic residency time of developing
      immature precursors for proper differentiation of a T cell subset.

PMID- 30218106
TI  - Proline provides site-specific flexibility for in vivo collagen.
AB  - Fibrillar collagens have mechanical and biological roles, providing tissues with
      both tensile strength and cell binding sites which allow molecular interactions
      with cell-surface receptors such as integrins. A key question is: how do
      collagens allow tissue flexibility whilst maintaining well-defined ligand binding
      sites? Here we show that proline residues in collagen glycine-proline
      hydroxyproline (Gly-Pro-Hyp) triplets provide local conformational flexibility,
      which in turn confers well-defined, low energy molecular compression-extension
      and bending, by employing two-dimensional 13C-13C correlation NMR spectroscopy on
      13C-labelled intact ex vivo bone and in vitro osteoblast extracellular matrix. We
      also find that the positions of Gly-Pro-Hyp triplets are highly conserved between
      animal species, and are spatially clustered in the currently-accepted model of
      molecular ordering in collagen type I fibrils. We propose that the Gly-Pro-Hyp
      triplets in fibrillar collagens provide fibril "expansion joints" to maintain
      molecular ordering within the fibril, thereby preserving the structural integrity
      of ligand binding sites.

PMID- 30218107
TI  - Exploring gravity with the MIGA large scale atom interferometer.
AB  - We present the MIGA experiment, an underground long baseline atom interferometer
      to study gravity at large scale. The hybrid atom-laser antenna will use several
      atom interferometers simultaneously interrogated by the resonant mode of an
      optical cavity. The instrument will be a demonstrator for gravitational wave
      detection in a frequency band (100 mHz-1 Hz) not explored by classical ground and
      space-based observatories, and interesting for potential astrophysical sources.
      In the initial instrument configuration, standard atom interferometry techniques
      will be adopted, which will bring to a peak strain sensitivity of [Formula: see
      text] at 2 Hz. This demonstrator will enable to study the techniques to push
      further the sensitivity for the future development of gravitational wave
      detectors based on large scale atom interferometers. The experiment will be
      realized at the underground facility of the Laboratoire Souterrain a Bas Bruit
      (LSBB) in Rustrel-France, an exceptional site located away from major
      anthropogenic disturbances and showing very low background noise. In the
      following, we present the measurement principle of an in-cavity atom
      interferometer, derive the method for Gravitational Wave signal extraction from
      the antenna and determine the expected strain sensitivity. We then detail the
      functioning of the different systems of the antenna and describe the properties
      of the installation site.

PMID- 30218110
TI  - Improved Automatic Morphology-Based Classification of Parkinson's Disease and
      Progressive Supranuclear Palsy.
AB  - OBJECTIVES: The overlapping symptoms of Parkinson's disease (PD) and progressive
      supranuclear palsy-Richardson's syndrome (PSP-RS) often make a correct clinical
      diagnosis difficult. The volume of subcortical brain structures derived from high
      resolution T1-weighted magnetic resonance imaging (MRI) datasets is frequently
      used for individual level classification of PD and PSP-RS patients. The aim of
      this study was to evaluate the benefit of including additional morphological
      features beyond the simple regional volume, as well as clinical features, and
      morphological features of cortical structures for an automatic classification of
      PD and PSP-RS patients. MATERIAL AND METHODS: A total of 98 high-resolution T1
      weighted MRI datasets from 76 PD patients, and 22 PSP-RS patients were available
      for this study. Using an atlas-based approach, the volume, surface area, and
      surface-area-to-volume ratio (SA:V) of 21 subcortical and 48 cortical brain
      regions were calculated and used as features for a support vector machine
      classification after application of a RELIEF feature selection method. RESULTS:
      The comparison of the classification results suggests that including all three
      morphological parameters (volume, surface area and SA:V) can considerably improve
      classification accuracy compared to using volume or surface area alone. Likewise,
      including clinical patient features in addition to morphological parameters also
      considerably increases the classification accuracy. In contrast to this,
      integrating morphological features of other cortical structures did not lead to
      improved classification accuracy. Using this optimal set-up, an accuracy of 98%
      was achieved with only one falsely classified PD and one falsely classified PSP
      RS patient. CONCLUSION: The results of this study suggest that clinical features
      as well as more advanced morphological features should be used for future
      computer-aided diagnosis systems to differentiate PD and PSP-RS patients based on
      morphological parameters.

PMID- 30218108
TI  - Prognostic significance of vitamin D receptor (VDR) gene polymorphisms in liver
      cirrhosis.
AB  - Several polymorphisms in the vitamin D receptor (VDR) are associated with the
      occurrence of chronic liver disease. Here, we investigated the association
      between BsmI, ApaI, TaqI and FokI VDR polymorphisms and the severity of liver
      cirrhosis in relation to serum cytokine and lipopolysaccharide binding protein
      (LBP) levels and their role on survival in cirrhotic patients. We found that
      patients harboring the BB genotype had higher MELD score, and they were mainly at
      CP stage C; patients harboring the AA genotype had increased LBP, IL-1beta and IL
      8 levels, and they were mostly at CP stage C; TT genotype carriers had higher
      MELD score and they were mainly at CP stage C and FF genotype carriers had lower
      IL-1beta levels when compared to Bb/bb, Aa/aa, Tt/tt and Ff/ff genotypes
      respectively. In the multivariate analysis ApaI, BsmI and TaqI polymorphisms were
      independently associated with liver cirrhosis severity. In the survival analysis,
      the independent prognostic factors were CP score, MELD and the FF genotype. Our
      results indicate that the ApaI, TaqI and BsmI polymorphisms are associated with
      the severity of liver cirrhosis, through the immunoregulatory process. Survival
      is related to the FF genotype of FokI polymorphism, imparting a possible
      protective role in liver cirrhosis.

PMID- 30218111
TI  - The influence of action-outcome contingency on motivation from control.
AB  - The sense of agency is defined as one's sense of control over one's actions and
      their consequences. A recent theory, the control-based response selection
      framework (Karsh and Eitam, Motivation from control: a response selection
      framework. The sense of agency, Oxford University Press, New York, 2015a),
      suggests that actions associated with a high sense of agency are intrinsically
      rewarding and thus motivate response selection. Previous studies support this
      theory by demonstrating that factors impacting on sense of agency (e.g.
      probability of an outcome following an action) also motivate selection of
      actions. Here we report a novel test of the control-based response selection
      framework in the domain of action-outcome contingency. The contingency between
      actions and their outcome has previously been demonstrated to impact the sense of
      agency, but its impact on the motivation to perform actions has not yet been
      examined. Participants were asked to press one of four buttons as randomly as
      possible. Each of the buttons was assigned a different probability of causing an
      outcome when pressed. Additionally, a contingency manipulation was employed where
      the probability of an outcome occurring in the absence of a button press was also
      varied in blocks throughout the experiment. Results demonstrated a significant
      influence of contingency on response speed, and a significant effect of
      probability on response selection, consistent with predictions from the control
      based response selection framework. Furthermore, some evidence was observed for a
      positive correlation between influence of contingency and autistic traits, with
      individuals with higher autistic traits showing a greater influence of
      contingency on reaction times. The current findings support the idea that actions
      associated with an increased sense of agency are intrinsically rewarding, and
      identify how individual differences may impact on this process.

PMID- 30218112
TI  - Correction to: Weight changes associated with antiepileptic mood stabilizers in
      the treatment of bipolar disorder.
AB  - In the original version of this article unfortunately two tables have been
      missing. By mistake they have been published as Supplementary Material. We
      apologize for any inconvenience caused. The original article has been corrected.

PMID- 30218114
TI  - Analytical ultracentrifugation (AUC): a seminal tool offering multiple solutions.
AB  - Analytical ultracentrifugation (AUC) remains a highly versatile and widely
      applicable tool for the analysis of macromolecules and their interactions. The
      current state-of-the-art was demonstrated at a recent international meeting held
      in Glasgow, Scotland, in July 2017, the 23rd International Analytical
      Ultracentrifugation Workshop and Symposium. This special issue showcases the
      reports made at the meeting, which concerned the application of AUC to a wide
      range of topics in biochemical and polymer science including antibody and
      membrane protein characterisation, and protein-carbohydrate interactions.
      Presentations on development and testing of new instrumentation and methods of
      analysis were a particular feature of the meeting, including the optimisation of
      experimental protocols, and the latest optimised computational approaches to
      experimental simulation and the modelling of macromolecular structures.

PMID- 30218115
TI  - Electrostatic mechanism of V600E mutation-induced B-Raf constitutive activation
      in colorectal cancer: molecular implications for the selectivity difference
      between type-I and type-II inhibitors.
AB  - The oncogenic mutation V600E in B-Raf activation loop (A-loop) has been
      frequently observed to cause drug resistance in colorectal cancer chemotherapy.
      Here, the molecular mechanism of V600E-induced conformational flipping of B-Raf
      activation loop (A-loop) is investigated systematically via continuum
      electrostatic analysis. It is found that substitution of the electroneutral
      Val600 residue with negatively charged glutamic acid Glu600 electrostatically
      destabilizes the inactive DFG-out conformation of B-Raf kinase and promotes its
      shifting to active DFG-in conformation. This is analogous with natural
      phosphorylation of Thr598 and/or Ser601 residues in A-loop to activate the
      kinase, that is, both the mutation and phosphorylation can introduce negative
      charge to B-Raf A-loop and then trigger the loop flipping. Energetic analysis
      reveals that the V600E mutation can affect inhibitor binding indirectly via
      regulation of kinase conformation. Type-I and type-II inhibitors respond
      distinctly to V600E mutation; the former is sensitized by the mutation, while the
      latter generally shows a low sensitivity to the mutation. Based on this
      guideline, the sophisticated type-I pan-kinase inhibitor Staurosporine as well as
      its analogs Midostaurin and Lestaurtinib are identified as potent mutant
      selective inhibitors by modeling analysis and kinase assay, which exhibit a
      moderate or high selectivity for B-RafV600E over B-RafWT (3.7-fold, 6.1-fold and
      > 3.1-fold, respectively).

PMID- 30218113
TI  - [Hyperhidrosis-aetiopathogenesis, diagnosis, clinical symptoms and treatment].
AB  - Although primary hyperhidrosis is a common disease, secondary symptomatic
      hyperhidrosis is rather rare. Primary hyperhidrosis is a complex neuropathic
      dysregulation with a genetic predisposition and is diagnosed when patients show
      pathologic sweating patterns and excessive sweating for at least 6 months and
      fulfill at least four of the following criteria: affected areas are axillae
      and/or palms and/or soles and/or forehead; symmetry; no night sweating; at least
      once a week; onset before the age of 25; positive family history; negative impact
      on daily activities. Frequently used therapies are topical aluminum salts and
      anticholinergics, iontophoresis in water, and intracutaneous botulinum toxin.
      Anticholinergics are also used as systemic treatment. Surgical procedures are
      used as a last result. Furthermore procedures using thermolysis have been
      developed.

PMID- 30218116
TI  - Development of a two-stage model system to investigate the mineralization
      mechanisms involved in idiopathic stone formation: stage 2 in vivo studies of
      stone growth on biomimetic Randall's plaque.
AB  - Idiopathic stone formers often form calcium oxalate (CaOx) stones that are
      attached to calcium phosphate (CaP) deposits in the renal tissue, known as
      Randall's plaques (RP). Plaques are suggested to originate in the renal tubular
      basement membrane and spread into the interstitial regions where collagen fibrils
      and vesicles become mineralized; if the epithelium is breached, the RP becomes
      overgrown with CaOx upon exposure to urine. We have developed a two-stage model
      system of CaP-CaOx composite stones, consisting of Stage (1) CaP mineralized
      plaque, followed by Stage (2) CaOx overgrowth into a stone. In our first paper in
      this series (Stage 1), osteopontin (and polyaspartate) were found to induce a non
      classical mineralization of porcine kidney tissues, producing features that
      resemble RP. For the Stage 2 studies presented here, biomimetic RPs from Stage 1
      were implanted into the bladders of rats. Hyperoxaluria was induced with ethylene
      glycol for comparison to controls (water). After 4 weeks, rats were sacrificed
      and the implants were analyzed using electron microscopy and X-ray microanalyses.
      Differences in crystal phase and morphologies based upon the macromolecules
      present in the biomimetic plaques suggest that the plaques have the capacity to
      modulate the crystallization reactions. As expected, mineral overgrowths on the
      implants switched from CaP (water) to CaOx (hyperoxaluric). The CaOx crystals
      were aggregated and mixed with organic material from the biomimetic RP, along
      with some amorphous and spherulitic CaOx near the "stone" surfaces, which seemed
      to have become compact and organized towards the periphery. This system was
      successful at inducing "stones" more similar to human idiopathic kidney stones
      than other published models.

PMID- 30218117
TI  - Longitudinal Examination of Bone Loss in Male Rats After Moderate-Severe
      Contusion Spinal Cord Injury.
AB  - To elucidate mechanisms of bone loss after spinal cord injury (SCI), we evaluated
      the time-course of cancellous and cortical bone microarchitectural deterioration
      via microcomputed tomography, measured histomorphometric and circulating bone
      turnover indices, and characterized the development of whole bone mechanical
      deficits in a clinically relevant experimental SCI model. 16-weeks-old male
      Sprague-Dawley rats received T9 laminectomy (SHAM, n = 50) or moderate-severe
      contusion SCI (n = 52). Outcomes were assessed at 2-weeks, 1-month, 2-months, and
      3-months post-surgery. SCI produced immediate sublesional paralysis and
      persistent hindlimb locomotor impairment. Higher circulating tartrate-resistant
      acid phosphatase 5b (bone resorption marker) and lower osteoblast bone surface
      and histomorphometric cancellous bone formation indices were present in SCI
      animals at 2-weeks post-surgery, suggesting uncoupled cancellous bone turnover.
      Distal femoral and proximal tibial cancellous bone volume, trabecular thickness,
      and trabecular number were markedly lower after SCI, with the residual cancellous
      network exhibiting less trabecular connectivity. Periosteal bone formation
      indices were lower at 2-weeks and 1-month post-SCI, preceding femoral cortical
      bone loss and the development of bone mechanical deficits at the distal femur and
      femoral diaphysis. SCI animals also exhibited lower serum testosterone than SHAM,
      until 2-months post-surgery, and lower serum leptin throughout. Our moderate
      severe contusion SCI model displayed rapid cancellous bone deterioration and more
      gradual cortical bone loss and development of whole bone mechanical deficits,
      which likely resulted from a temporal uncoupling of bone turnover, similar to the
      sequalae observed in the motor-complete SCI population. Low testosterone and/or
      leptin may contribute to the molecular mechanisms underlying bone deterioration
      after SCI.

PMID- 30218118
TI  - [Reconstruction of the urinary tract after an intestinal fistula].

PMID- 30218119
TI  - Utilization of Coronary Artery to Aorta for the Early Detection of Kawasaki
      Disease.
AB  - Timely diagnosis of coronary involvement is paramount in Kawasaki disease (KD) as
      it can be associated with long-term morbidity. However, echocardiographic
      measurements of coronary artery dilation in KD are inconsistent and not
      proficient for all abnormal arteries. The purpose of this study was to
      investigate more valuable indices and determine their sensitivity and specificity
      for early diagnosis of coronary involvement in KD. We performed this
      retrospective study in 218 children. All patients underwent laboratory and
      echocardiographic evaluations upon admission. We measured the size of the left
      main coronary artery (LMA), left anterior descending coronary artery (LAD), right
      coronary artery (RCA), and aorta (Ao), and calculated the LMA/Ao, LAD/Ao, and
      RCA/Ao ratios. We also calculated the cut-off values of each index using receiver
      operating characteristic curves. LMA, LAD, and RCA measurements did not correlate
      with white blood cell count, platelet count, erythrocyte sedimentation rate, C
      reactive protein level, or brain natriuretic peptide level. The LMA measurement
      was associated with hemoglobin, hematocrit, and iron saturation. LAD/Ao was
      correlated with white blood cell and platelet counts (P < 0.05), whereas RCA/Ao
      was correlated with ferritin level (P < 0.05). The cut-off value of LMA/Ao was
      0.2, with a sensitivity of 85% and specificity of 70%. Individual coronary
      artery/Ao ratios might provide helpful insight for detection of coronary
      abnormality in KD in the acute phase. Further investigation is essential to
      clarify prompt early diagnosis of coronary involvement in KD.

PMID- 30218120
TI  - Assessment of Fish Embryo Survival and Growth by In Situ Incubation in Acidic
      Boreal Streams Undergoing Biomining Effluents.
AB  - The applicability of an in situ incubation method in monitoring the effects of
      metal mining on early life stages of fish was evaluated by investigating the
      impacts of a biomining technology utilizing mine on the mortality, growth, and
      yolk consumption of brown trout (Salmo trutta) and whitefish (Coregonus
      lavaretus) embryos. Newly fertilized eggs were incubated from autumn 2014 to
      spring 2015 in six streams under the influence of the mine located in North
      Eastern Finland and in six reference streams. Although the impacted streams
      clearly had elevated concentrations of several metals and sulfate, the embryonic
      mortality of the two species did not differ between the impacted and the
      reference streams. Instead, particle accumulation to some cylinders had a
      significant impact on the embryonic mortality of both species. In clean
      cylinders, mortality was higher in streams with lower minimum pH. However, low pH
      levels were evident in both the reference and the mine-impacted groups. The
      embryonic growth of neither species was impacted by the mining activities, and
      the growth and yolk consumption of the embryos was mainly regulated by water
      temperature. Surprisingly, whitefish embryos incubated in streams with lower
      minimum pH had larger body size. In general, the applied in situ method is
      applicable in boreal streams for environmental assessment and monitoring,
      although in our study, we did not observe a specific mining impact differing from
      the effects of other environmental factors related to catchment characteristics.

PMID- 30218121
TI  - Be unafraid ... to try something new or challenging.

PMID- 30218122
TI  - Non-destructive characterisation of the Elephant Moraine 83227 meteorite using
      confocal Raman, micro-energy-dispersive X-ray fluorescence and Raman-scanning
      electron microscope-energy-dispersive X-ray microscopies.
AB  - The application of a non-destructive analytical procedure to characterise the
      mineral phases in meteorites is a key issue in order to preserve this type of
      scarce materials. In the present work, the Elephant Moraine 83227 meteorite,
      found in Antarctica in 1983 and originated from 4 Vesta asteroid, was analysed by
      micro-Raman spectroscopy, micro-energy-dispersive X-ray fluorescence and the
      structural and chemical analyser (Raman spectroscopy coupled with scanning
      electron microscopy-energy-dispersive spectroscopy) working in both point-by
      point and image modes. The combination of all these techniques allows the
      extraction of, at the same time, elemental, molecular and structural data of the
      studied microscopic area of the meteorite. The most relevant results of the
      Elephant Moraine 83227 were the finding of tridymite for the first time in a 4
      Vesta meteorite, along with quartz, which means that the meteorite suffered high
      temperatures at a certain point. Moreover, both feldspar and pyroxene were found
      as the main mineral phases in the sample. Ilmenite, apatite, chromite and
      elemental sulphur were also detected as secondary minerals. Finally, calcite was
      found as a weathering product, which was probably formed in terrestrial
      weathering processes of the pyroxene present in the sample. Besides, Raman
      spectroscopy provided information about the conditions that the meteorite
      experienced; the displacements in some feldspar Raman bands were used to estimate
      the temperature and pressure conditions to which the Elephant Moraine 83227 was
      subjected, because we obtained both low and high formation temperature feldspar.

PMID- 30218123
TI  - Quantitative analysis of cefquinome considering different matrix compositions of
      bovine colostrum and raw milk.
AB  - A robust liquid chromatography-tandem mass spectrometry method was developed and
      comprehensively validated for the quantification of cefquinome considering the
      changing matrix composition from bovine colostrum to raw milk. Sample preparation
      consisted of addition of isotopically labeled cefquinome internal standard prior
      to protein precipitation of 2 g colostrum or milk followed by solid-phase
      extraction. A wide concentration range from 1 to 5000 ng cefquinome per gram of
      colostrum or milk was quantified using a 3200 QTRAP tandem mass spectrometer in
      positive ionization mode with electrospray ionization. Validation was performed
      according to the European Commission Decision 2002/657/EC guidelines. Matrix
      comprehensive in-house validation included analytical limits CCalpha and CCbeta,
      recovery, precision and calibration curves with prediction intervals, storage
      conditions, and evaluation of robustness based on factorial effect analysis. The
      detection limit was 0.2 ng cefquinome per gram of colostrum or milk. Recovery was
      between 98.4 and 99.4% for cefquinome concentrations from 4 to 240 ng/g. None of
      the investigated validation factors (matrix, storage of extracts, lot of SPE
      cartridges, and operators) exerted an influence higher than +/- 3.2%, indicating
      that these factors make relatively low contributions to the respective combined
      measurement uncertainties. The comprehensively validated method enables routine
      residue control purposes and to monitor the pharmacokinetics of cefquinome in
      bovine colostrum and raw milk. In particular, residue depletion curves of
      cefquinome from high concentrations in first milking after treatment to
      concentrations far below the maximum residue limit can be measured.

PMID- 30218124
TI  - Toehold integrated molecular beacon system for a versatile non-enzymatic
      application.
AB  - A molecular beacon (MB) is an oligonucleotide hybridization probe with a hairpin
      shaped structure that leads to specific and instantaneous nucleic acid
      hybridization, enabling a variety of applications. However, integration of
      additional module sequences interferes with the performance of MBs and increases
      the complexity of sequence design. Herein, we develop and characterize a toehold
      integrated molecular beacon (ToMB) strategy for nucleic acid hybridization, where
      the reaction rate can be flexibly regulated by a target-induced MB conformational
      switch. Using this basic mechanism, the ToMB is capable of identifying nucleic
      acids with high specificity and a wider linearity range compared with the
      conventional molecular beacon system. We further applied the ToMB to the
      construction of a hybridization chain reaction system and a basic OR logic gate
      VJHto explore its programmability and versatility. Our results strongly suggest
      that the novel ToMB can act as a powerful nano-module to construct universal and
      multifunctional biosensors or molecular computations. Graphical abstract
      Molecular beacon is employed as a flexible and switchable spacer to control the
      toehold-mediated strand displacement reaction.

PMID- 30218125
TI  - Graphene quantum dots-based nano-biointerface platform for food toxin detection.
AB  - Due to the similar electrochemical properties to graphene oxide (GO), graphene
      quantum dots (GQDs) are considered as a highly potential candidate for designing
      an electrochemical biosensor. In this report, GQDs were synthesized having an
      average diameter of 7 nm and utilized for the fabrication of an electrochemical
      immunosensor for the detection of food toxin, aflatoxin B1 (AFB1). An
      electrophoretic deposition technique was utilized to deposit the chemically
      synthesized GQDs onto indium tin oxide (ITO)-coated glass substrate. Further, the
      monoclonal antibodies of AFB1 were covalently immobilized onto deposited
      electrode GQDs/ITO using EDC-NHS as a crosslinker. The structural and
      morphological studies of GQDs and conjugated anti-AFB1 with GQDs have been
      investigated using UV-visible spectroscopy, photoluminescence spectroscopy, Raman
      spectroscopy, transmission electron microscopy, scanning electron microscopy
      techniques, etc. The electrochemical impedance spectroscopy and cyclic
      voltammetry measurements were carried out for electrical characterization and
      biosensing studies. This simple monodisperse GQDs-based platform yields
      heterogeneous electron transfer (97.63 * 10-5 cm s-1), the time constant (0.005
      s) resulting in improved biosensing performance. The electrochemical immunosensor
      shows high sensitivity 213.88 Omega (ng mL-1)-1 cm-2. The limit of detection for
      standard samples and contaminated maize samples was found to be 0.03 ng mL-1 and
      0.05 ng g-1, respectively, which is lower than the maximum acceptable limit
      according to the European Union. This result indicates its potential application
      for aflatoxin B1 detection in food contents. Graphical abstract ?.

PMID- 30218126
TI  - A versatile quantitative microdroplet elemental imaging method optimised for
      integration in biochemical workflows for low-volume samples.
AB  - Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) analysis
      of MU-droplets is becoming an attractive alternative for detecting and
      quantifying elements in biological samples. With minimal sample preparation
      required and detection limits comparable to solution nebulisation ICP-MS, MU
      droplets have substantial advantages over traditional elemental detection,
      particularly for low volumes, such as aliquots taken from samples required for
      multiple independent biochemical assays, or fluids and tissues where elements of
      interest exist at native concentrations not suited to the necessary dilution
      steps required for solution nebulisation ICP-MS. However, the characteristics of
      MU-droplet residue deposition are heavily dependent on the matrix, and potential
      effects on signal suppression or enhancement have not been fully characterised.
      We present a validated and flexible high-throughput method for quantification of
      elements in MU-droplets using LA-ICP-MS imaging and matrix-matched external
      calibrants. Imaging the entire MU-droplet area removes analytical uncertainty
      arising from the often-heterogenous distribution when compared to radial or
      bisecting line scans that capture only a small portion of the droplet residue. We
      examined the effects of common matrices found in a standard biochemistry
      workflow, including native protein and salt contents, as well as reagents used in
      typical preparation steps for concurrent biochemical assays, such as total
      protein quantification and enzyme activity assays. We found that matrix
      composition results in systemic, concentration-dependent signal enhancement and
      suppression for carbon, whereas high sodium content has a specific space-charge
      like suppression effect on high masses. We confirmed the accuracy of our method
      using both a certified serum standard (SeronormTM L1) and independent
      measurements of analysed samples by solution nebulisation ICP-MS, then tested the
      specificity and reproducibility by examining spinal cord tissue homogenates from
      SOD1-G93A transgenic mice with a known molecular phenotype of increased copper-
      and zinc-binding superoxide dismutase-1 expression and altered copper-to-zinc
      stoichiometry. The method presented is rapid and transferable to multiple other
      biological matrices and allows high-throughput analysis of low-volume samples
      with sensitivity comparable to standard solution nebulisation ICP-MS protocols.
      Graphical Abstract ?.

PMID- 30218127
TI  - MMP-11 as a biomarker for metastatic breast cancer by immunohistochemical
      assisted imaging mass spectrometry.
AB  - MMP-11 is a member of the matrix metalloproteinase family (MMPs) which are
      overexpressed in cancer cells, stromal cells and the adjacent microenvironment.
      The MMP protein family encompasses zinc-dependent endopeptidases that degrade the
      extracellular matrix (ECM), facilitating the breakdown of the basal membrane and
      matrix connective tissues. This function is believed to be important in cancer
      development and metastasis. This paper investigated a gold nanoparticle-based
      immunohistochemical assay to visualise the distribution of MMP-11 in human breast
      cancer tissues from eight patients with and without metastases by employing laser
      ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The expression
      of MMP-11 was increased and more heterogeneous in metastatic specimens compared
      to non-metastatic tumour samples. These findings demonstrate that imaging breast
      tumours by LA-ICP-MS may be a useful tool to aid the prognosis and treatment of
      breast cancer. As an example, samples of two patients are presented who were
      diagnosed with matching characteristics and grades of breast cancer. Although
      both patients had a similar prognosis and treatment, only one developed
      metastases.

PMID- 30218128
TI  - A label-free MALDI TOF MS-based method for studying the kinetics and inhibitor
      screening of the Alzheimer's disease drug target beta-secretase.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI TOF MS) is a well-established method with a unique set of qualities
      including sensitivity, minute sample consumption, and label-free detection, all
      of which are highly desired in enzyme assays. On the other hand, the application
      of MALDI TOF MS is usually limited by high concentrations of MS-incompatible
      compounds in the reaction mixture such as salts or organic solvents. Here, we
      introduce kinetic and inhibition studies of beta-secretase (BACE1), a key enzyme
      of the progression of Alzheimer's disease. Compatibility of the enzyme assay with
      MALDI TOF MS was achieved, providing both a complex protocol including a
      desalting step designed for rigorous kinetic studies and a simple mix-and-measure
      protocol designed for high-throughput inhibitor screening. In comparison with
      fluorescent or colorimetric assays, MALDI TOF MS represents a sensitive, fast,
      and label-free technique with minimal sample preparation. In contrast to other MS
      based methodological approaches typically used in drug discovery processes, such
      as a direct injection MS or MS-coupled liquid chromatography or capillary
      electrophoresis, MALDI TOF MS enables direct analysis and is a highly suitable
      approach for high-throughput screening. The method's applicability is strongly
      supported by the high correlation of the acquired kinetic and inhibition
      parameters with data from the literature as well as from our previous research.
      Graphical abstract ?.

PMID- 30218129
TI  - Quorum Sensing Autoinducer(s) and Flagellum Independently Mediate EPS Signaling
      in Vibrio cholerae Through LuxO-Independent Mechanism.
AB  - Vibrio cholerae, the Gram-negative bacterium causing lethal diarrheal disease
      cholera, forms biofilm on solid surfaces to gain adaptive advantage for
      successful survival in aquatic reservoirs. Expression of exopolysaccharide (EPS),
      an extracellular matrix material, has been found critical for biofilm-based
      environmental persistence. In a subset of epidemic-causing V. cholerae, absence
      of flagellum but not motility was identified to induce elevated exopolysaccharide
      expression. Identification of the role played by quorum sensing autoinducer
      molecules, i.e., cholera autoinducer 1 (CAI-1) and autoinducer 2 (AI-2) as well
      as central regulator LuxO on EPS expression in the subset was explored. Deletion
      mutations were introduced in vital genes responsible for synthesizing CAI-1
      (cqsA), AI-2 (luxS), flagellum (flaA), LuxO (luxO), flagellar motor (motX), and
      VpsR (vpsR) in the model strain MO10. Subsequent phenotypic alterations in terms
      of colony morphology, EPS expression, biofilm formation, and transcription level
      of relevant genes were analyzed. Autoinducer cross-feeding experiment confirmed
      the role of autoinducers in EPS signaling. Results reveal that autoinducers and
      flagellum are the two major EPS signaling units in this subset where one unit
      becomes predominant for EPS production in absence of the other. Moreover, either
      unit exerts negative influence on EPS induction by the other. Both the EPS
      signaling cascades are independent of LuxO contribution and essentially involve
      sodium-driven flagellar motor and VpsR. A cell density and flagellum-mediated,
      but LuxO-independent, EPS signaling mechanism is considered to be functional in
      these organisms that confers their survival fitness.

PMID- 30218130
TI  - Global Networks of Symbiodinium-Bacteria Within the Coral Holobiont.
AB  - Scleractinian corals form the framework of coral reefs and host abundant and
      diverse microbial communities that are fundamental to their success. A very
      limited number of studies have examined the co-occurrence of multiple partners
      within the coral 'holobiont' and their pattern of specificity over different
      geographical scales. In this study, we explored two molecular sequence datasets
      representing associations between corals and dinoflagellates in the genus
      Symbiodinium and between corals and bacteria, across the globe. Through a network
      theory approach, we characterised patterns of co-occurrences between bacteria and
      Symbiodinium with 13 coral genera across six water basins. The majority of the
      bacteria-Symbiodinium co-occurrences were specific to either a coral genus or
      water basin, emphasising both coral host and environment as important factors
      driving the diversity of coral assemblages. Yet, results also identified bacteria
      and Symbiodinium that were shared by multiple coral genera across several water
      basins. The analyses indicate that shared co-occurrences are independent of the
      phylogenetic and biogeographic relationship of coral hosts.

PMID- 30218131
TI  - Predicting extinction phenotype to optimize fear reduction.
AB  - Fear conditioning is widely employed to study dysregulations of the fear system.
      The repeated presentation of a conditioned stimulus in the absence of a
      reinforcer leads to a decrease in fear responding-a phenomenon known as
      extinction. From a translational perspective, identifying whether an individual
      might respond well to extinction prior to intervention could prove important to
      treatment outcomes. Here, we test the hypothesis that CO2 reactivity predicts
      extinction phenotype in rats, and that variability in CO2 reactivity as well as
      extinction long-term memory (LTM) significantly predicts orexin activity in the
      lateral hypothalamus (LH). Our results validate a rat model of CO2 reactivity and
      show that subcomponents of behavioral reactivity following acute CO2 exposure
      explain a significant portion of the variance in extinction LTM. Furthermore, we
      show evidence that variability in CO2 reactivity is also significantly predictive
      of orexin activity in the LH, and that orexin activity, in turn, significantly
      accounts for LTM variance. Our findings open the possibility that we may be able
      to use CO2 reactivity as a screening tool to determine if individuals are good
      candidates for an extinction/exposure-based approach.

PMID- 30218132
TI  - Erratum to: Three-dimensional thoracoscopic vertebral body replacement at the
      thoracolumbar junction.
AB  - Erratum to:Oper Orthop Traumatol 2018 https://doi.org/10.1007/s00064-018-0559-3
      The article was wrongly published under the article type "Review". Please note
      that the article is an "Original Paper".The publisher apologizes to authors and
      ....

PMID- 30218133
TI  - [Reconstruction of the middle phalangeal base of the finger using an
      osteocartilaginous autograft from the hamate].
AB  - OBJECTIVE: Restoration of proximal interphalangeal joint stability with
      preservation of mobility by reconstruction of the middle phalanx base using an
      osteochondral graft from the carpometacarpal joint surface of the hamate.
      INDICATIONS: Acute and older isolated destruction of the palmar middle phalanx
      base >25%. CONTRAINDICATIONS: Destruction of the head of the proximal phalanx,
      advanced chondropathia of the head of the proximal phalanx, extensive soft tissue
      injury with loss of skin coverage at the proximal interphalangeal joint. SURGICAL
      TECHNIQUE: The fractured middle phalangeal base is debrided and the defect is
      replaced by a size-matched autograft from the dorsal carpometacarpal hamate
      osteoarticular surface that is secured in place with miniscrews. POSTOPERATIVE
      MANAGEMENT: Immobilization for 2 weeks in a below-elbow cast in intrinsic plus
      position. Subsequent immobilization by a splint including the distal and proximal
      interphalangeal joint. RESULTS: Healing was achieved in 100% with restoration of
      joint congruity in 12 of 13 cases and slight subluxation in 1 case. Follow up was
      possible in 9 cases after 22 +/- 16 (5-51) months. The average range of motion in
      the reconstructed joint achieved 0/9/73 degrees , grip strength 82% of the
      unaffected side. Of the 9 patients, 5 developed a mild flexion contracture of the
      proximal interphalangeal joint. The DASH score achieved 4 +/- 3 (0-8) points,
      pain at rest was 1 +/- 2 (0-5), pain at exercise 2 +/- 2 (0-5) on a visual
      analogue scale (0-10). All patients were satisfied and willing to undergo the
      procedure again. According to the literature, reconstruction of the base of the
      middle phalanx by using an osteochondral graft from the hamate is a reliable
      procedure to restore stability and mobility of the joint.

PMID- 30218134
TI  - [Present hormonal birth control and the risk of breast cancer].

PMID- 30218135
TI  - [Active surveillance and postponed operation after neoadjuvant radiochemotherapy
      for oesophageal cancer-findings of the preSANO study].

PMID- 30218136
TI  - Risk factors for brain metastasis in patients with small cell lung cancer without
      prophylactic cranial irradiation.
AB  - BACKGROUND: This study aimed to determine the risk factors for brain metastasis
      (BM) and the prognostic factors for overall survival (OS) in patients with small
      cell lung cancer without prophylactic cranial irradiation (PCI). PATIENTS AND
      METHODS: Limited stage small cell lung cancer (LS-SCLC) patients achieving a
      complete response (CR) or partial response (PR) were enrolled into this study
      between January 2010 and December 2016. We retrospectively evaluated the
      influencing factors for time to BM and overall survival (OS). RESULTS: A total of
      153 patients were enrolled into this study. Sixty-eight developed BM during the
      follow-up period. For the whole cohort, the 1- and 2-year BM rates were 29.4 and
      41.2%, respectively. Multivariate analysis showed that T stage (hazard ratio [HR]
      = 2.27, P = 0.024), neutrophil-to-lymphocyte ratio (NLR; HR = 2.07, P = 0.029),
      time to thoracic radiotherapy (HR = 0.34, P = 0.002) and chemotherapy cycles (HR
      = 0.49, P = 0.036) were the independent influencing factors of time to BM. Only
      NLR (HR = 2.11, P = 0.005) and time to thoracic radiotherapy (HR = 1.95, P =
      0.011) were independent prognostic factors of OS. Of the 68 patients developing
      BM, those with BM occurring as the first relapse (42/68) had better OS than the
      others (39.5 months vs 23.0 months, P = 0.016). CONCLUSION: LS-SCLC patients
      without PCI had a high risk of BM. High T stage, high NLR, early thoracic
      radiotherapy and fewer chemotherapy cycles were the risk factors of BM. Further
      research is needed to confirm the results.

PMID- 30218138
TI  - The 47th annual meeting of the Japanese society of neuroradiology : 16-17
      February 2018, Tsukuba, Japan.

PMID- 30218137
TI  - Postoperative local fractionated radiotherapy for resected single brain
      metastases.
AB  - PURPOSE: Evaluation of postoperative fractionated local 3D-conformal radiotherapy
      (3DRT) of the resection cavity in brain metastases. PATIENTS AND METHODS: Between
      2011 and 2016, 57 patients underwent resection of a single, previously untreated
      (37/57, 65%) or recurrent (20/57, 35%) brain metastasis (median maximal diameter
      3.5 cm [1.1-6.5 cm]) followed by 3DRT. For definition of the gross tumor volume
      (GTV), the resection cavity was used and for the clinical target volume (CTV),
      margins of 1.0-1.5 cm were added. Median dose was 48.0 Gy (30.0-50.4 Gy) in 25
      (10-28) fractions; most patients had 36.0-42.0 Gy in 3.0 Gy fractions (n = 16,
      EQD210Gy 39.0-45.5 Gy) or 40.0-50.4 Gy in 1.8-2.0 Gy fractions (n = 37, EQD210Gy
      39.3-50.0 Gy). RESULTS: Median follow-up was 18 months. Local control rates were
      83% at 1 year and 78% at 2 years and were significantly influenced by histology
      (breast cancer 100%, non-small lung cancer 87%, melanoma 80%, colorectal cancer
      26% at 2 years, p = 0.006) and resection status (p < 0.0001), but not by EQD210Gy
      or size of the planning target volume (median 96.7 ml [16.7-282.8 ml]). At 1 and
      2 years, 74% and 52% of the patients were free from distant brain metastases.
      Salvage procedures were applied in 25/27 (93%) of recurrent patients. Survival
      was 68% at 1 year and 41% at 2 years and was significantly improved in younger
      patients (p = 0.006) with higher Karnofsky performance score (p < 0.0001) and
      without prior radiotherapy (54% vs. 9% at 2 years, p = 0.006). No cases of
      radiographic or symptomatic radionecrosis were observed. CONCLUSION: Adjuvant
      fractionated local 3DRT is highly effective in radiosensitive, completely
      resected metastases and should be considered for treating large resection
      cavities as an alternative to postoperative stereotactic single dose or
      hypofractionated radiosurgery.

PMID- 30218140
TI  - Predicting mixed-meal measured glycaemic index in healthy subjects.
AB  - PURPOSE: To determine the influence of meal composition on the glycaemic impact
      of different carbohydrate staples, and the accuracy of "adjusted calculated meal
      GI" compared with "measured mixed-meal GI". METHODS: In a non-blind randomized
      crossover trial fasted healthy subjects consumed four dinner-type mixed meals of
      realistic serving size comprising a carbohydrate staple of either mashed potato,
      pasta, rice or a glucose drink, combined with fixed portions of boiled carrots,
      poached salmon and herb sauce. Blood samples collected between 0 and 180 min were
      analysed for glucose and insulin concentrations. Adjusted calculated meal GI
      values were determined against a 50 g reference glucose drink, and compared to
      corresponding measured mixed-meal GIs, supplemented with data from four previous
      mixed-meal postprandial glycaemic response studies. RESULTS: The common
      carbohydrate staples, and the glucose drink, ingested as part of the salmon mixed
      meal induced a significantly lower post-prandial relative glycaemic response
      (RGR) and concurrent higher relative insulin response than the same amount of
      staple eaten alone. Adjusted calculated mixed-meal GI closely predicted measured
      mixed-meal GI in healthy subjects for 15 out of 17 mixed meals examined, showing
      the need to account for effects of fat and protein when predicting measured mixed
      meal GI. Further, we showed the validity of using customarily consumed food
      amounts in mixed-meal postprandial RGR study design. CONCLUSIONS: Adjusted
      calculated mixed-meal GI appears a useful model to predict measured mixed-meal GI
      in healthy subjects and with further development and validation could aid
      nutrition research and rational design of healthy meals for personalized
      nutrition and particular consumer groups.

PMID- 30218141
TI  - Late onset meningocele in a case of meningocele manque.

PMID- 30218142
TI  - Physiologic closure time of the metopic suture in South Australian infants from
      3D CT scans.
AB  - : Metopic synostosis is a craniofacial condition characterised by the premature
      fusion of the metopic suture. This early fusion restricts frontal bone growth
      [17] and has significant impacts on the developing infant during a critical phase
      of rapid growth and development [4]. Diagnosis of the condition is usually
      achieved by clinical assessment, followed by a three-dimensional computed
      tomography (3D CT) scan, verifying premature metopic suture fusion. PURPOSE: This
      retrospective study aims to investigate the timing of metopic suture fusion in
      the developing infant in an Australian subpopulation. METHODS: The study
      evaluates metopic suture fusion in 258 cranial 3D CT scans of children aged 0-24
      months over a 5-year period (2011-2016), scanned at Women's and Children's
      Hospital. RESULTS: The findings suggest that the age range over which physiologic
      metopic suture fusion occurs is larger than previously reported. CONCLUSIONS: The
      approximate range for physiologic fusion was found to be 3-19 months and patients
      with fusion within this range can be considered normal. Complete suture fusion is
      expected by 19 months. Additionally, results indicate suture fusion prior to 3
      months is abnormal and diagnostically indicative of metopic synostosis.

PMID- 30218143
TI  - Melanoma-prone families: new evidence of distinctive clinical and histological
      features of melanomas in CDKN2A mutation carriers.
AB  - Germline mutations on the CDKN2A gene, the most important known genetic factors
      associated with cutaneous melanomas (CMs), predispose carriers to multiple
      primary CMs (MPMs) with higher frequency and younger onset compared to non
      carriers. Most of the largest published studies concerning clinical and
      histological characteristics of CMs with CDKN2A mutation carriers did not specify
      if the described CMs are first or subsequent to the first, and they used sporadic
      CMs from non-genotyped patients as controls. We conducted a single-centre
      observational study to compare clinical and histological CM features of 32
      unrelated carriers (MUT) of 5 germline CDKN2A mutations (one of which was never
      previously described) compared to 100 genotyped wild-type (WT) patients. We
      stratified the data based on time of diagnosis, anatomical site and histological
      subtype of CMs, demonstrating several significant unreported differences between
      the two groups. MUT developed a higher number of dysplastic nevi and MPMs. We
      proved for the first time that anatomical distribution of CMs in MUT was
      independent of gender, unlike WTs. MUTs developed in situ and superficial
      spreading melanomas (SSMs) more frequently, with significantly higher number of
      SSMs on the head/neck. In MUTs, Breslow thickness was significantly lower for all
      invasive CMs. When CMs were stratified on the basis of the time of occurrence,
      statistical significance was maintained only for SSMs subsequent to the first. In
      WTs, Clark level was significantly higher, and ulceration was more prevalent than
      in MUTs. Significant differences in ulceration were observed only in SSMs. In
      nodular CMs, we did not find differences in terms of Breslow thickness or
      ulceration between WTs and MUTs. In situ CMs developed 10 years earlier in MUTs
      with respect to WTs, whereas no significant differences were observed in invasive
      CMs. In contrast to those reported previously by other authors, we did not find a
      difference in skin phototype.

PMID- 30218145
TI  - Using Google Trends to assess global public interest in osteoarthritis.
AB  - To evaluate global public interest in osteoarthritis by assessing changes in
      Internet search popularity of the disease over a 10-year period. Google Trends
      was used to obtain search popularity scores for the word "osteoarthritis" (OA)
      between January 2004 and June 2018. We also analyzed changes in search volume
      relative to changes in search patterns for all health topics. Search interest in
      OA was high relative to all other health searches over the given timeframe.
      Overall, searches for OA steadily decreased between May 2004 and December 2012
      and then steadily rose from January 2013 to April 2018. We also found consistent
      annual fluctuations over the pre-specified time range, with biannual peaks
      typically correlating with national and global awareness days. Biannual dips
      occurred with changes in seasonal patterns. Google searches for OA have steadily
      increased in recent years. Awareness initiatives, like World Arthritis Day, may
      be a reason for the public to search for information on OA. It may be helpful for
      physicians to search the Internet themselves for websites that provide accurate
      and high-quality information to recommend to their patients.

PMID- 30218144
TI  - Frailty in surgical patients.
AB  - OBJECTIVE: To describe the current definitions, aetiology, assessment tools and
      clinical implications of frailty in modern surgical practice. BACKGROUND: Frailty
      is a critical issue in modern surgical practice due to its association with
      adverse health events and poor post-operative outcomes. The global population is
      rapidly ageing resulting in more older patients presenting for surgery. With
      this, the number of frail patients presenting for surgery is also increasing.
      Despite the identification of frailty as a significant predictor of poor health
      outcomes, there is currently no consensus on how to define, measure and diagnose
      this important syndrome. METHODS: Relevant references were identified through
      keyword searches of the Cochran, MEDLINE and EMbase databases. RESULTS: Despite
      the lack of a gold standard operational definition, frailty can be conceptualised
      as a state of increased vulnerability resulting from a decline in physiological
      reserve and function across multiple organ systems, such that the ability to
      withstand stressors is impaired. Multiple studies have shown a strong association
      between frailty and adverse peri-operative outcomes. Frailty may be assessed
      using multiple tools; however, the ideal tool for use in a clinical setting has
      yet to be identified. Despite the association between frailty and adverse
      outcomes, few interventions have been shown to improve outcomes in these
      patients. CONCLUSION: Frailty encompasses a group of individuals at high risk of
      adverse post-operative outcomes. Further work exploring ways to optimally assess
      and target interventions towards these patients should be the focus of ongoing
      research.

PMID- 30218146
TI  - The effects of embryonic hypoxic programming on cardiovascular function and
      autonomic regulation in the American alligator (Alligator mississippiensis) at
      rest and during swimming.
AB  - Reptilian embryos naturally experience fluctuating oxygen levels in ovo, and
      developmental hypoxia has been established to have long-term impacts on
      cardiovascular function in vertebrates. In the present study, we investigated the
      impact of developmental 21% (normoxia) and 10% O2 (hypoxia) on juvenile (4-year
      old) American alligator cardiovascular function in animals at rest and during
      swimming. In both experimental groups, combined right aortic and right subclavian
      blood flow approximately doubled during swimming. Carotid blood flow increased
      during swimming in the hypoxia-programmed animals only, and both carotid and left
      aortic blood flow reached higher values in swimming hypoxic-programmed animals
      compared to the normoxic group. However, pulmonary blood flow, which increased
      two to threefold during swimming (in both groups), was higher in normoxic
      programmed animals at both rest and swimming. The differences between programming
      groups were preserved after cholinergic blockade (atropine), but reduced by
      adrenergic receptor antagonists (propranolol and phentolamine). Propranolol and
      phentolamine also blunted the incremental increases in blood flows during
      swimming, which was especially clear in the hypoxia-programmed animals.
      Alteration in adrenergic control and relative cardiac size (which was increased
      in hypoxic-programmed alligators) may account for the differences between the
      experimental groups.

PMID- 30218147
TI  - Sources of Ca2+ for contraction of the heart tube of Tenebrio molitor
      (Coleoptera: Tenebrionidae).
AB  - Insect and vertebrate hearts share the ability to generate spontaneously their
      rhythmic electrical activity, which triggers the fluid-propelling mechanical
      activity. Although insects have been used as models in studies on the impact of
      genetic alterations on cardiac function, there is surprisingly little information
      on the generation of the inotropic activity in their hearts. The main goal of
      this study was to investigate the sources of Ca2+ for contraction in Tenebrio
      molitor hearts perfused in situ, in which inotropic activity was assessed by the
      systolic variation of the cardiac luminal diameter. Increasing the pacing rate
      from 1.0 to 2.5 Hz depressed contraction amplitude and accelerated relaxation. To
      avoid inotropic interference of variations in spontaneous rate, which have been
      shown to occur in insect heart during maneuvers that affect Ca2+ cycling,
      experiments were performed under electrical pacing at near-physiological rates.
      Raising the extracellular Ca2+ concentration from 0.5 to 8 mM increased
      contraction amplitude in a manner sensitive to L-type Ca2+ channel blockade by
      D600. Inotropic depression was observed after treatment with caffeine or
      thapsigargin, which impair Ca2+ accumulation by the sarcoplasmic reticulum (SR).
      D600, but not inhibition of the sarcolemmal Na+/Ca2+ exchanger by KB-R7943,
      further depressed inotropic activity in thapsigargin-treated hearts. From these
      results, it is possible to conclude that in T. molitor heart, as in vertebrates:
      (a) inotropic and lusitropic activities are modulated by the heart rate; and (b)
      Ca2+ availability for contraction depends on both Ca2+ influx via L-type channels
      and Ca2+ release from the SR.

PMID- 30218149
TI  - The trigeminal root: an anatomical study using magnetic resonance imaging.
AB  - PURPOSE: The trigeminal root is a remarkable structure that can be an original
      site of trigeminal neuralgia. However, few studies have explored the detailed
      anatomy of it with neuroimages. The aim of the present study was to characterize
      the trigeminal root using magnetic resonance (MR) imaging. METHODS: Thin-sliced,
      axial T2-weighted imaging and coronal constructive interference in steady-state
      (CISS) sequence were performed for a total of 167 patients. RESULTS: On axial T2
      weighted imaging, three divisions of the main trigeminal sensory root were
      unequivocally delineated in 36% of the 95 patients. Sixty-three percent of the
      Meckel's cave was bilaterally adjacent to the petrous portion of the internal
      carotid artery. On CISS sequence, course of the main trigeminal sensory root was
      well delineated in all of the 72 patients. The accessory sensory and motor
      rootlets were identified in 38% and 56% of 144 sides, respectively. Levels of the
      main trigeminal roots at the original site and entrance into the Meckel's as well
      morphology of the original segment of the main trigeminal sensory root were
      variable. Furthermore, in 24% of sides, three divisions of the main trigeminal
      sensory root were clearly delineated, arranged in variable manners. In 20% sides,
      segments of the superior cerebellar artery had a contact with the main trigeminal
      sensory root and motor rootlets. CONCLUSIONS: Coronal CISS sequence is useful for
      delineating the trigeminal root. Anatomy of the trigeminal root presents
      considerable inter- and intra-individual variability that can influence the
      symptoms of trigeminal neurovascular compression.

PMID- 30218150
TI  - Visualization of the vidian canal and nerve using magnetic resonance imaging.
AB  - BACKGROUND AND PURPOSE: Few studies have investigated the vidian nerve (VN) and
      vidian canal (VC) with the use of magnetic resonance imaging (MRI). The present
      study aimed to characterize the VC and VN using MRI. MATERIALS AND METHODS: A
      total of 91 patients underwent thin-sliced, contrast MRI. The course of the VC
      and VN and the relationships with relevant structures were analyzed. RESULTS: The
      VC was identified in 95% of axial images on the right side and in 93% on the
      left. The course of the VC was delineated in 99% of serial coronal images on both
      sides. The VN location in the VC was highly variable. The course of the VC and
      transmitting VN was delineated in 95% of sagittal images on the right side and in
      91% on the left. The mean length of the VC was 19.8 mm on the right side and 19.3
      mm on the left. Topographical relationships between the anterior genu of the
      petrous internal carotid artery and the posterior end of the vidian canal could
      be classified into three types. Of these, the type terminating at the level of
      the petrous carotid was the most predominant, comprising 76% of 182 sides. The
      course of the VC and transmitting VN could be classified into four types. The
      straight type was the most predominant and was found in 41%. CONCLUSIONS: The VC
      and transmitting VN are structures with variable morphologies. Contrast MRI is
      useful for delineating the VC and VN.

PMID- 30218151
TI  - The maximum chemiluminescence intensity predicts severe neutropenia in
      gemcitabine-treated patients with pancreatic or biliary tract cancer.
AB  - PURPOSE: To assess the predictive ability of the maximum chemiluminescence
      intensity (CImax) for severe neutropenia (SN) during neoadjuvant
      chemo(radio)therapy [NAC(RT)] in patients with advanced pancreatic or biliary
      tract cancer. METHODS: Clinicopathological variables and blood test data before
      NAC(RT) were evaluated in 64 patients with advanced pancreatic or biliary tract
      cancer who received gemcitabine plus tegafur/gimeracil/oteracil as NAC(RT).
      RESULTS: Thirty-nine patients (60.9%) developed Grade 3-4 SN. The median time
      between commencing NAC(RT) and the onset of SN was 15 (range 10-36) days. SN
      occurred during the NAC period, not the RT period. The CImax, neutrophil count,
      serum interleukin-6 level, C-reactive protein level, complement C3 titer, serum
      complement titer, and 50.0% hemolytic unit of complement before NAC(RT) were
      significantly lower in patients with SN than in those without SN (P < 0.05).
      Multivariate analysis confirmed the CImax to be the sole independent predictor of
      SN (P < 0.05). The optimal threshold for the CImax was 46,000 RLU/s. The
      sensitivity and specificity were 46.2% and 80.0%, respectively. Majority of the
      patients (81.8%) with a low CImax before NAC(RT) experienced SN during NAC(RT).
      CONCLUSIONS: CImax before NAC(RT) predicts SN during NAC(RT) in patients with
      advanced pancreatic or biliary tract cancer.

PMID- 30218152
TI  - Adjustable V-Flap Epicanthoplasty Based on Desired Eyelid Morphology.
AB  - Eyelid shape is one key distinctive feature of the Asian eye. The presence of
      epicanthal folds is a common eyelid defect of Asians. Different surgical
      techniques have been developed to correct epicanthal folds. However, potential
      problems with these techniques are emerging, such as difficulty in design,
      recurrence and/or prominent scarring after surgery, and restricted application
      together with double eyelidplasty. An improved epicanthoplasty technique with
      high simplicity and flexibility is imperative. From October 2000 to March 2017,
      we performed V-flap epicanthoplasty procedures on 423 Asian patients. The whole
      procedure, including V-shaped skin incision, myotomy and pilication of the medial
      canthal ligament was performed layer by layer. A similar palpebral fissure
      distance and inner canthal distance were acquired with this surgical operation.
      Besides, this surgical technique will not cause limitations on double eyelid
      morphology when a double blepharoplasty is performed at the same period. The V
      flap epicanthoplasty we described here is able to fully correct the epicanthal
      folds with a simple and flexible design, and the surgery can be adjusted
      according to patient needs for desired double eyelid shape. Satisfactory results
      were ideally achieved with no recurrence and finer scar.Level of evidence V This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these evidence-based medicine ratings, please refer to the
      table of contents or the online instructions to authors www.springer.com/00266 .

PMID- 30218153
TI  - Nasal Elongation with Septal Half Extension Graft: Modification of Conventional
      Septal Extension Graft Using Minimal Septal Cartilage.
AB  - BACKGROUND: In Asian rhinoplasty, a septal extension graft can be used for both
      tip projection and derotation of the alar cartilage. However, patients often do
      not have enough harvestable septal cartilage to create the septal extension
      graft. We therefore devised a method with which to fix the derotated alar
      cartilage with a small amount of septal cartilage. METHODS: From January 2012 to
      December 2016, 23 patients underwent short nose correction with a septal half
      extension graft made of septal cartilage and were postoperatively monitored for
      at least 6 months. The alar cartilage was completely separated from the adjacent
      structures, especially the scroll area and hinge complex, for caudal derotation.
      The septal half extension graft was then harvested from the septal cartilage and
      secured to the caudal septum and the lateral crura of the alar cartilage.
      Photographs of the patients were compared immediately before surgery and 1 year
      after surgery. RESULTS: Of the 23 patients, 21 (91%) had satisfactory results
      without short nose recurrence. Two (9%) patients developed recurrence:
      undercorrection and poor tip projection in one patient each. Aesthetic assessment
      of short nose correction was performed by comparing the columellar labial angle
      before and after surgery. Our method reduced the columellar labial angle by 6.2%
      (paired t test, p < 0.05, t = 31.698). CONCLUSION: In patients who cannot undergo
      conventional septal extension graft due to insufficient amounts of septal
      cartilage, the septal half extension graft could be a promising alternative
      technique for short nose correction with minimal septal cartilage harvesting.
      LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 30218154
TI  - Free Desmosine is a Sensitive Marker of Smoke-Induced Emphysema.
AB  - PURPOSE: While the elastin-specific crosslinks, desmosine and isodesmosine (DID),
      are increased in blood, urine, and sputum of patients with clinically documented
      pulmonary emphysema, the usefulness of DID in detecting early lung injury remains
      untested. To this end, our laboratory has measured DID in a hamster model of
      smoke-induced emphysema, involving only minimal alveolar wall damage. METHODS:
      Animals were either treated with cigarette smoke for 2 h/day, 5 days/week, or
      exposed only to room air (controls) for a period of 3 months. DID levels in
      bronchoalveolar lavage fluid (BALF) and whole lungs were determined at monthly
      intervals, using liquid chromatography and tandem mass spectrometry. Lung surface
      area was also determined, as a measure of airspace enlargement. RESULTS: The
      portion of BALF DID not bound to peptides (free DID) was significantly higher in
      smoke-exposed animals at 2 months (9.2 vs 4.4 pg/mg protein; p < 0.05), whereas
      total BALF DID showed no significant increases over the course of the study, and
      total lung DID remained unchanged. There was a mild, but significant, loss of
      lung surface area in the smoke-exposed group at 2 months (28.8% vs 25.2%, p <
      0.05), which showed no further progression, consistent with the return of free
      DID to control levels at 3 months. CONCLUSIONS: These findings support the
      hypothesis that free DID are sensitive indicators of smoke-induced lung injury.
      Measurement of free DID in smokers with minimally decreased lung mass may help
      determine the utility of this parameter as a test for incipient pulmonary
      emphysema.

PMID- 30218156
TI  - [Is hand hygiene according to the guidelines possible in intensive care units?]

PMID- 30218155
TI  - Imaging Features of Chronic Bronchitis with Preserved Ratio and Impaired
      Spirometry (PRISm).
AB  - PURPOSE: The purpose of the study was to investigate the quantitative chest
      tomographic features of chronic bronchitis with preserved ratio and impaired
      spirometry (PRISm), including airway wall area, emphysema index, and lung
      capacity. METHODS: An observational, cross-sectional study of 343 patients at the
      Ninth Hospital of Xi'an Affiliated Hospital of Xi'an Jiaotong University between
      October 2014 and September 2017. The patients were divided into three groups: 77
      cases of chronic bronchitis with normal lung function (forced expiratory volume
      in one second/forced vital capacity) (FEV1/FVC > 70%, FEV1%pred > 80%), 80 cases
      of chronic bronchitis with PRISm (FEV1/FVC > 70%, FEV1%pred < 80%), and 186 cases
      of the early chronic obstructive pulmonary disease (COPD) (FEV1/FVC < 70%,
      FEV1%pred > 50%, that is, Global Initiative for Chronic Obstructive Lung Disease
      (GOLD) grade 1 + 2). We compared and analyzed the differences in imaging between
      the chronic bronchitis with PRISm and the other two groups. RESULTS: Compared
      with the early COPD group, the PRISm group revealed significant differences in
      airway wall area, emphysema index, and lung capacity (P < 0.05). Compared with
      the chronic bronchitis with normal lung function group, the PRISm group showed
      increased WA%LUL5, decreased lung capacity, and higher mean lung density.
      CONCLUSION: In terms of airway wall area and emphysema index, patients with
      chronic bronchitis with PRISm were essentially no different than those with
      chronic bronchitis without abnormal spirometry, whereas for symptoms, they are
      more like GOLD 1 and 2 patients. Our findings show that it is not yet clear
      whether it constitutes an intermediate stage of chronic bronchitis with normal
      lung function that progression to early COPD.

PMID- 30218157
TI  - Graphene oxide wrapped with gold nanorods as a tag in a SERS based immunoassay
      for the hepatitis B surface antigen.
AB  - A composite consisting of graphene oxide and gold nanorods (GO-GNRs) was designed
      for the trace determination of hepatitis B surface antigen (HBsAg) using surface
      enhanced Raman spectroscopy (SERS). GO contains numerous carboxy and hydroxy
      groups on its surface and therefore can serve as the substrate for decoration
      with GNRs and for immobilizing antibody against HBsAg. The GNRs (carrying the
      SERS probe 2-mercaptopyridine) exhibit high SERS activity, and this improves the
      sensitivity of the biosensor. The antibody on the GO-GNRs binds HBsAg with high
      specificity, and it results in excellent selectivity. The SERS signal (measured
      at 1002 cm-1) increases in the 1-1000 pg.mL-1 HBsAg concentrations range, and the
      limit of detection is 0.05 pg.mL-1 (at an S/N ratio of 3). The immunoassay
      achieves the sensitive and selective determination of HBsAg in serum and expands
      the potential application of GO-GNR based SERS tag in clinical research.
      Graphical abstract A novel graphene oxide-gold nanorod (GO-GNRs) based surface
      enhanced Raman scattering (SERS) tag for immunoassay was designed. It allows for
      sensitive and selective determination of HBsAg in serum. The method is expected
      to expand the potential application in the environment, in medicine and in food
      analysis.

PMID- 30218158
TI  - Shigella and Enteroinvasive Escherichia Coli.
AB  - Shigella and enteroinvasive Escherichia coli (EIEC) are gram-negative bacteria
      responsible for bacillary dysentery (shigellosis) in humans, which is
      characterized by invasion and inflammatory destruction of the human colonic
      epithelium. Different EIEC and Shigella subgroups rose independently from
      commensal E. coli through patho-adaptive evolution that included loss of
      functional genes interfering with the virulence and/or with the intracellular
      lifestyle of the bacteria, as well as acquisition of genetic elements harboring
      virulence genes. Among the latter is the large virulence plasmid encoding for a
      type three secretion system (T3SS), which enables translocation of virulence
      proteins (effectors) from the bacterium directly into the host cell cytoplasm.
      These effectors enable the pathogen to subvert epithelial cell functions,
      promoting its own uptake, replication in the host cytosol, and dissemination to
      adjacent cells while concomitantly inhibiting pro-inflammatory cell death.
      Furthermore, T3SS effectors are directly involved in Shigella manipulation of
      immune cells causing their dysfunction and promoting cell death. In the current
      chapter, we first describe the evolution of the enteroinvasive pathovars and then
      summarize the overall knowledge concerning the pathogenesis of these bacteria,
      with a particular focus on Shigella flexneri. Subversion of host cell functions
      in the human gut, both epithelial and immune cells, by different virulence
      factors is especially highlighted.

PMID- 30218159
TI  - A catalytic cleavage strategy for fluorometric determination of Hg(II) based on
      the use of a Mg(II)-dependent split DNAzyme and hairpins conjugated to gold
      nanoparticles.
AB  - A catalytic cleavage strategy was developed for the fluorometric determination of
      Hg(II). The method is based on the use of a Mg(II)-dependent split DNAzyme.
      Fluorophore labeled hairpins were conjugated to gold nanoparticles (AuNPs) upon
      which fluorescence is quenched. Thymine-Hg(II)-thymine (T-Hg(II)-T) interaction
      causes the two DNA sequences to form an entire enzyme-strand DNA (E-DNA). The E
      DNA bind to the hairpins on the AuNPs to form a Mg(II)-dependent DNAzyme
      structure. The circular cleavage of hairpins results in a signal amplification
      and in the recovery of fluorescence. The assay has a limit of detection (LOD) as
      low as 80 pM of Hg(II). This LOD is comparable to those obtained with other
      amplification strategies. The method was successfully applied to the
      determination of Hg(II) in Chinese herbs (Atractylodes macrocephala Koidz).
      Graphical abstract Schematic of a catalytic cleavage strategy based on Mg(II)
      dependent split DNAzyme for fluorometric determination of Hg(II).

PMID- 30218160
TI  - Chronic hyperglycemia with elevated glycated hemoglobin level and its association
      with postoperative acute kidney injury after a major laparoscopic abdominal
      surgery in diabetes patients.
AB  - BACKGROUND: The relationship between preoperative hyperglycemia and postoperative
      acute kidney injury (AKI) occurrence in non-cardiac surgery including
      laparoscopic surgery remains unclear. This study aimed to assess the relationship
      between preoperative chronic hyperglycemia and postoperative AKI occurrence after
      a major laparoscopic abdominal surgery. METHODS: We retrospectively reviewed
      medical records of diabetic patients (>= 20 years old) who underwent elective
      major laparoscopic abdominal surgery procedures between 2010 and 2016. Patients
      were divided into two groups based on a cut-off value of hemoglobin A1c (HbA1c)
      at 6%. Serum creatinine value was used for the diagnosis of AKI, and all
      assessments and diagnoses of postoperative AKI were performed on 0-3
      postoperative days (POD) using the criteria of Kidney Disease: Improving Global
      Outcomes. RESULTS: In all, 1885 patients were included in the final analysis, and
      patients were divided into the following groups: < 6.0% group with 1257 patients
      (66.7%), and >= 6.0% group with 628 patients (33.3%). Sixty-nine patients (3.7%)
      were diagnosed with postoperative AKI within 3 POD. Multivariable logistic
      regression analysis showed no significant difference in the incidence rate of
      postoperative AKI between the HbA1c >= 6.0% group and the < 6.0% group (odds
      ratio 1.10, 95% confidence interval 0.57-2.15; P = 0.770). In addition, there was
      no significant interaction between preoperative HbA1c group and exposure to acute
      hyperglycemia (serum glucose > 200 mg/dL) for incidence of AKI on POD 0-3 (P =
      0.181). CONCLUSIONS: In diabetic patients, preoperative chronic hyperglycemia is
      not associated with postoperative AKI occurrence within 3 POD after a major
      laparoscopic abdominal surgery.

PMID- 30218161
TI  - Land consumption monitoring: an innovative method integrating SAR and optical
      data.
AB  - In this paper, the use of synthetic aperture radar (SAR) for the monitoring of
      land consumption is analyzed. The paper presents an automatic procedure that
      integrates SAR and optical data, which can be effectively used to generate land
      consumption maps or update existing maps. The main input of the procedure is a
      series of SAR amplitude images acquired over a given geographical area and
      observation period. The main assumption of the procedure is that land consumption
      is associated with an increase of the SAR amplitude values. Such an increase is
      detected in the SAR amplitude time series using an automatic Bayesian algorithm.
      The results based on the SAR amplitude are then filtered using an NDVI map
      derived from optical imagery. The effectiveness of the proposed procedure is
      illustrated using SAR data from the Sentinel-1 and TerraSAR-X sensors, and
      optical data from the Sentinel-2 sensor.

PMID- 30218162
TI  - Double nerve transfer for restoration of hand grasp and release in C7 tetraplegia
      following complete cervical spinal cord injury.
AB  - Cervical spinal cord injury (SCI) can cause tetraplegia. Nerve transfer has been
      routinely utilized for reconstruction of hand in brachial plexus injuries. Here,
      we report reconstruction of finger flexion (hand grasp) and extension (hand
      release) in a victim of cervical spinal cord injury with tetraplegia. We also
      focus on importance of extension phase in restoration of hand function in the
      tetraplegic case, in addition to provision of a detailed description of both
      operations including text, photographs, and a video. We used double nerve
      transfer, namely brachialis branches of musculocutaneous nerve to anterior
      interosseous nerve (AIN) and supinator branch of radial nerve to posterior
      interosseous nerve (PIN). We found that brachialis nerve transfer to AIN (for
      finger flexion) and supinator branch nerve transfer to PIN (for finger extension)
      can provide finger flexion and extension simultaneously. Brachialis nerve
      transfer to AIN and supinator branch nerve transfer to PIN may be an acceptable
      surgical technique to restore hand grasp and release in tetraplegia after SCI.

PMID- 30218163
TI  - Intensive care unit admission in patients with T cell lymphomas: clinical
      features and outcome.
AB  - T cell non-Hodgkin lymphomas (T-NHLs) are aggressive malignancies which have a
      high risk of life-threatening complications. However, their prognosis in the
      intensive care unit (ICU) setting has not yet been assessed. We conducted a study
      including 87 ICU patients either with newly diagnosed T-NHLs or those undergoing
      first-line therapy admitted between January 1, 2000, and December 31, 2014. The
      primary subtypes were peripheral T cell lymphoma (PTCL) (n = 41, 47%), anaplastic
      large-cell lymphoma (ALCL) (n = 13, 15%), and adult T-leukaemia/lymphoma (ATLL)
      (n = 11, 13%). Six in every ten patients had malignancy-related complications
      (haemophagocytic syndrome 37%, tumour lysis syndrome 18% and hypercalcaemia 9%),
      while infections accounted for one quarter of ICU admissions. Nine fungal
      infections were documented, including six invasive aspergillosis. Urgent
      chemotherapy was started in the ICU in 59% of the patients, and urgent surgery
      was required in 13%. ICU and day-90 mortality were 22% and 41%, respectively.
      Multivariate analysis showed that SOFA score at day 1, age, sepsis and
      haemophagocytic syndrome were independent predictors of day-90 mortality.
      Compared to 66 ICU-matched controls with non-Hodgkin B cell lymphomas, patients
      with T-NHLs had a similar ICU survival. Overall survival rates of patients with T
      cell NHLs and B cell NHLs were 20% and 46%, respectively (hazard ratio for death
      associated with T cell NHLs 2.00 [1.12-3.58]). Patients with T cell NHLs had a
      very poor long-term outcome. Although the high rate of short-term survival
      suggests that an ICU trial is a reasonable option for patients newly diagnosed
      for the malignancy, extended stay in the ICU or further readmission should be
      considered only for highly selected patients who respond to the haematological
      treatment.

PMID- 30218164
TI  - Autopsy findings in patients with acute myeloid leukemia and non-Hodgkin lymphoma
      in the modern era: a focus on lung pathology and acute respiratory failure.
AB  - We aimed to report autopsy findings in patients with acute myeloid leukemia (AML)
      and non-Hodgkin lymphoma (NHL) in the modern era, and also to focus on lung
      pathology in the subgroup of patients with acute respiratory failure (ARF) of
      unknown etiology, which is associated with especially high mortality rates.
      Charts and autopsy reports of 107 patients (59 AML and 48 NHL) autopsied between
      2003 and 2018 were reviewed. More than 50% of patients had missed major diagnoses
      found at autopsy with 95% of lungs displaying abnormal findings. Malignant
      infiltration in at least one organ was observed in about 70% of patients with
      either no complete remission or relapse at the time of death (n = 92) versus 20%
      in patients without signs of active malignancy (n = 15) (p = 0.001). In patients
      with ARF of unknown etiology (n = 59), the proportion of malignant lung
      infiltration was 27% and equilibrated with bacterial pneumonias (29%), fungal
      pneumonias represented 8%, and isolated alveolar damage or pulmonary edema were
      the only findings in 32% of patients. Overall, 85% of patients with ARF of
      unknown etiology had either relapsed or not achieved remission at time of death
      and 80% of patients with malignant lung infiltration had ARF of unknown etiology.
      Ninety percent of malignant infiltration and fungal infections were observed in
      patients with no complete remission or relapse. Autopsy remains valuable in AML
      and NHL patients; besides infections, malignant infiltration is a significant
      contributor to ARF of unknown etiology and is rarely diagnosed ante mortem.

PMID- 30218165
TI  - [Complex regional pain syndrome].
AB  - Complex regional pain syndrome (CRPS) is not a very common yet typical
      complication of extremity trauma in the daily practice of a trauma surgeon. The
      pathophysiology of this puzzling disease is still not completely understood and
      its impact on the patient cannot be overestimated. However, advantages have been
      made in diagnostics and therapy. While a multitude of different diagnostic
      systems has led to confusion in the past, we now have an internationally
      accepted, validated and easy to reproduce diagnostic algorithm in the form of the
      Budapest criteria. The adequate therapy is still a field for debate, but there is
      now a broad choice of conservative and interventional treatments for the out- and
      inpatient setting.

PMID- 30218166
TI  - [The "sacrificial electrode" : A safe option for the management of pacemaker
      infections in pacemaker-dependent patients].
AB  - As the number of cardiac implantable electronic devices (CIEDs) increases, so
      does the need to revise such systems. Pacemaker-dependent patients with a CIED
      infection are particulary challenging for the attending physician. Here, the CIED
      cannot simply be removed without replacement. Gold standard therapy is a
      sufficient, prolonged antibiosis, the complete removal of the CIED, and the
      installation of a temporary pacemaker system - usually by means of a transvenous
      probe or epimyocardial probe via thoracotomy. The disadvantages of these
      therapies are the insecure positioning of the unfixed transvenous or the
      invasiveness of the epimyocardial probes. Alternatively, we have since 2015
      established a concept with the so-called "sacrificial" electrode. For this
      purpose - during the explantation of the infected CIED - a conventional,
      transvenous screw electrode is anchored via the subclavian vein in the right
      ventricle and is then connected cutaneously to an aggregate. If the anti
      infective therapy is successful, a new CIED is implanted whenever possible over
      the contralateral side in the usual way. Stimulation via the sacrificial
      electrode can be stopped and the probe removed. This method is technically easy
      to perform and offers great advantages: no dislocation of the probe and
      maintained patient mobility.

PMID- 30218167
TI  - Degenerative spondylolisthesis: a prospective cross-sectional cohort study on the
      role of weakened anterior abdominal musculature on causation.
AB  - PURPOSE: Degenerative spondylolisthesis (DS) is a degenerative condition of the
      spine which, unlike others, is more common in a female population. Previous
      studies have highlighted possible causative factors such as facet tropism and
      pregnancy as reasons for this. This study sets out to assess the possible link
      between abdominal musculature and DS. METHOD: A prospective cross-sectional
      cohort study in a single surgeon practice assessed all patients aged over 50
      years attending for degenerative lumbar spinal complaints. Patient demographics,
      as well as the number of pregnancies, children, abdominal surgical procedures,
      were recorded. RESULTS: We found 205 patients that met our inclusion criteria (98
      Males/107 Females). Women with multiple pregnancies (p = 0.036) and abdominal
      surgeries (p = 0.021) were more likely to develop DS. Males with ventral hernias
      were more likely to have developed DS (p = 0.004). CONCLUSION: This study
      highlights the important role that the abdominal musculature plays in
      stabilization of the spine and highlights its potential role as a factor in the
      development of DS. These slides can be retrieved under Electronic Supplementary
      Material.

PMID- 30218168
TI  - Factors associated with having an indication for surgery in adult spinal
      deformity: an international european multicentre study.
AB  - PURPOSE: The aim of this study was to evaluate factors that distinguish between
      patients with adult spinal deformity (ASD) with and without an indication for
      surgery, irrespective of their final treatment. METHODS: Baseline variables
      (demographics, medical history, outcome measures, coronal, sagittal and
      neurologic parameters) were evaluated in a multicentre, prospective cohort of
      patients with ASD. Multivariable analyses were carried out for idiopathic and
      degenerative patients separately with the dependent variable being "indication
      for surgery" and baseline parameters as independent variables. RESULTS: In total,
      342 patients with degenerative ASD and 624 patients with idiopathic ASD were
      included in the multivariable models. In patients with degenerative ASD, the
      parameters associated with having an indication for surgery were greater self
      rated disability on the Oswestry Disability Index [odds ratio (OR) 1.04, 95%
      confidence interval (CI) 1.02-1.07] and a lower thoracic kyphosis (OR 0.97 95% CI
      0.95-0.99), whereas in patients with idiopathic ASD, it was lower (worse) SRS
      self-image scores (OR 0.45 95% CI 0.32-0.64), a higher value for the major Cobb
      angle (OR 1.03 95% CI 1.01-1.05), lower age (OR 0.96 95% CI 0.95-0.98), prior
      decompression (OR 3.76 95% CI 1.00-14.08), prior infiltration (OR 2.23 95% CI
      1.12-4.43), and the presence of rotatory subluxation (OR 1.98 95% CI 1.11-3.54)
      and sagittal subluxation (OR 4.38 95% CI 1.61-11.95). CONCLUSION: Specific sets
      of variables were found to be associated with an indication for surgery in
      patients with ASD. These should be investigated in relation to patient outcomes
      for their potential to guide the future development of decision aids in the
      treatment of ASD. These slides can be retrieved under Electronic Supplementary
      Material.

PMID- 30218169
TI  - Advances in understanding the association between Down syndrome and Hirschsprung
      disease (DS-HSCR).
AB  - The clinical association between Trisomy 21 (Down syndrome) and aganglionosis
      (Hirschsprung disease; DS-HSCR) is well-established, being of the order of 5% and
      remains the most common congenital association with Hirschsprung disease.
      However, little consensus exists as to the possible etiologic and genetic factors
      influencing this association. Recent research has identified a number of levels
      at which development of the enteric nervous system is potentially affected in
      Trisomy 21. These include a decreased central pool of available neuroblasts for
      migration into the enteric nervous system, abnormal neuroblast type, poor
      synaptic nerve function and early germline gene-related influences on the
      migrating neuroblasts due to genetic mutations of a number of important
      developmental genes, and possible somatic mutations resulting from alterations in
      the local tissue microenvironment. In this paper, we review available evidence
      for this association. In addition, we provide evidence of both germline and
      somatic gene mutations suggesting causation. Although the picture is complex,
      recent associations between specific RET proto-oncogene variations have been
      shown to be significant in Down syndrome patients with Hirschsprung disease, as
      they probably interfere with vital RET functions in the development of the
      autonomic and enteric nervous systems, increasing the risk of disturbed normal
      function. In addition, we explore potential role of other facilitatory influence
      of other susceptibility genes as well as potential other chromosome 21 gene
      actions and the microenvironment on the Down syndrome gastro-intestinal tract.
      The various ways in which trisomy of chromosome influences the enteric nervous
      system are becoming clearer. The sum of these effects influences the outcome of
      surgery in Down syndrome patients with Hirschsprung Disease.

PMID- 30218170
TI  - Home intravenous versus oral antibiotics following appendectomy for perforated
      appendicitis in children: a randomized controlled trial.
AB  - PURPOSE: To compare the effect of home intravenous (IV) versus oral antibiotic
      therapy on complication rates and resource utilization following appendectomy for
      perforated appendicitis. METHODS: This was a randomized controlled trial of
      patients aged 4-17 with surgically treated perforated appendicitis from January
      2011 to November 2013. Perforation was defined intraoperatively and divided into
      three grades: I-contained perforation, II-localized contamination to right
      gutter/pelvis, and III-diffuse contamination. Patients were randomized to
      complete a ten-day course of home antibiotic therapy with either IV ertapenem or
      oral amoxicillin-clavulanate. Thirty-day postoperative complication rates
      including abscess, readmission, wound infection, and charges were compared.
      RESULTS: Eighty-two patients were enrolled. Forty four (54%) were randomized to
      the IV group and 38 (46%) to the oral group. IV patients were older (12.3 +/- 3.6
      versus 10.1 +/- 3.6, p < 0.05) with higher BMI (20.9 +/- 5.8 versus 17.9 +/- 3.5,
      p < 0.05). There were no differences in gender, comorbidities, or perforation
      grade (I-20.4% vs. 26.3%, II-36.4% vs. 34.2%, III-43.2% vs. 39.5%, all p > 0.05).
      Comparing IV to oral, there was no difference in length of stay (4.4 +/- 1.5
      versus 4.4 +/- 2.0 days, p > 0.05), postoperative abscess rate (11.6% vs. 8.1%, p
      > 0.05), or readmission rate (14.0% vs. 16.2%, p > 0.05). Hospital and outpatient
      charges were higher in the IV group (p < 0.0001). CONCLUSION: Oral antibiotics
      had equivalent outcomes and incurred fewer charges than IV antibiotics following
      appendectomy for perforated appendicitis.

PMID- 30218171
TI  - Accurate quantification of T-cells expressing PD-1 in patients on anti-PD-1
      immunotherapy.
AB  - Increasing numbers of trials employing anti-PD-1 immunotherapy emphasize the
      requirement for predictive biomarkers of clinical response. Many studies examine
      the cell surface expression of PD-1 and other key regulators of T-cell activation
      and inhibition. Here, we compared common commercially available anti-PD-1
      diagnostic antibodies and tested whether they can bind the PD-1 receptor in the
      presence of the therapeutic antagonists pembrolizumab and nivolumab. We observed
      that currently no antibodies are available that can reliably stain all PD-1
      receptors on T-cells from patients treated with anti-PD-1 antibodies.
      Furthermore, none of the diagnostic antibodies detected the entire population of
      PD-1+ T-cells relative to indirect staining using the therapeutic antibodies
      themselves. To overcome this problem, here we present a reliable method for
      quantifying PD-1 expression on immune cells from treated patients which can be
      included in any conventional flow or mass cytometry antibody panel used for
      patient monitoring.

PMID- 30218173
TI  - Comparison between support vector machine and deep learning, machine-learning
      technologies for detecting epiretinal membrane using 3D-OCT.
AB  - PURPOSE: In this study, we compared deep learning (DL) with support vector
      machine (SVM), both of which use three-dimensional optical coherence tomography
      (3D-OCT) images for detecting epiretinal membrane (ERM). METHODS: In total, 529
      3D-OCT images from the Tsukazaki hospital ophthalmology database (184 non-ERM
      subjects and 205 ERM patients) were assessed; 80% of the images were divided for
      training, and 20% for test as follows: 423 training (non-ERM 245, ERM 178) and
      106 test (non-ERM 59, ERM 47) images. Using the 423 training images, a model was
      created with deep convolutional neural network and SVM, and the test data were
      evaluated. RESULTS: The DL model's sensitivity was 97.6% [95% confidence interval
      (CI), 87.7-99.9%] and specificity was 98.0% (95% CI, 89.7-99.9%), and the area
      under the curve (AUC) was 0.993 (95% CI, 0.993-0.994). In contrast, the SVM
      model's sensitivity was 97.6% (95% CI, 87.7-99.9%), specificity was 94.2% (95%
      CI, 84.0-98.7%), and AUC was 0.988 (95% CI, 0.987-0.988). CONCLUSION: DL model is
      better than SVM model in detecting ERM by using 3D-OCT images.

PMID- 30218172
TI  - DNA methylation marker to estimate the breast cancer cell fraction in DNA
      samples.
AB  - Estimation of the cancer cell fraction in breast cancer tissue is important for
      exclusion of samples unsuitable for multigene prognostic assays and a variety of
      molecular analyses for research. Here, we aimed to establish a breast cancer cell
      fraction marker based on DNA methylation. First, we screened genes unmethylated
      in non-cancerous mammary tissues and methylated in breast cancer tissues using
      microarray data from the TCGA database, and isolated 12 genes. Among them, four
      genes were selected as candidate marker genes without a high incidence of copy
      number alterations and with broad coverage across patients. Bisulfite
      pyrosequencing analysis of additional breast cancer biopsy specimens purified by
      laser capture microdissection (LCM) excluded two genes, and a combination of SIM1
      and CCDC181 was finally selected as a fraction marker. In further additional
      specimens without LCM purification, the fraction marker was substantially
      methylated (>= 20%) with high incidence (50/51). The cancer cell fraction
      estimated by the fraction marker was significantly correlated with that estimated
      by microscopic examination (p < 0.0001). Performance of a previously established
      marker, HSD17B4 methylation, which predicts therapeutic response of HER2-positive
      breast cancer to trastuzumab, was improved after the correction of cancer cell
      fraction by the fraction marker. In conclusion, we successfully established a
      breast cancer cell fraction marker based on DNA methylation.

PMID- 30218174
TI  - Post-mortem thermal angiography: a pilot study on swine coronary circulation.
AB  - Thermal imaging (TI) allows the detection of thermal patterns emitted from
      objects as a function of their temperature in the long-infrared spectrum and
      produces visible images displaying temperature differences. The aim of this pilot
      study was to test TI to visualize the coronary circulation of swine hearts.
      Thirty swine hearts were prepared for ex situ coronarography, and thermal images
      were acquired through a FlirOne thermal camera (FLIR Systems(r)) paired with a
      Google Android Smartphone. Coronary arteries were cannulated, namely the anterior
      interventricular artery, the circumflex branch of the left coronary artery, and
      the right coronary artery. The heart was cooled, and contrast medium (CM)
      consisting of distilled water heated to 40  degrees C was injected in a coronary
      vessel, while thermal images were captured. These steps were repeated for each
      coronary vessel and under experimentally simulated coronary heart disease.
      Thermal imaging coronarography (TIC) allowed a clear representation of the
      morphology and course of the coronary vessels and of experimentally simulated
      coronary heart disease, moreover, demonstrated to be easy to perform during or
      after autopsies on ex situ hearts, non-destructive, reproducible, and cheap. On
      the basis of these preliminary results, TIC might allow a subsequent more focused
      and comprehensive cardiopathological examination of the heart, which remains
      mandatory for the definitive diagnosis of coronary heart disease. Although these
      preliminary results seem encouraging, further systematic studies on human hearts,
      both normal and pathological, are necessary for estimating the sensitivity and
      specificity of the proposed method and to draw any definitive conclusion.

PMID- 30218175
TI  - Allele frequencies of 15 autosomal STRs in Chinese Nakhi and Yi populations.
AB  - Genetic characterization of ethnically and geographically diverse populations via
      short tandem repeats (STRs) is relevant to various fundamental and applied areas
      of forensic genetics, population studies, and even molecular anthropology. In the
      present study, genetic polymorphisms of 15 autosomal STR loci were firstly
      obtained from 918 individuals (495 Nakhis and 423 Yis) residing in the foothills
      of the Himalayas. The cumulative powers of discrimination and probabilities of
      exclusion in the two studied ethnic groups were both larger than
      0.999999999999999982 and 0.9999961, respectively. Genetic similarities and
      differences among 61 populations were subsequently investigated by pairwise
      Cavalli-Sforza genetic distance, multidimensional scaling plots, principal
      component analysis, and phylogenetic relationship reconstruction. Both Nakhi and
      Yi had the genetically close relationships with Yunnan Bai and distinct
      relationships with Xinjiang Turkic-speaking populations (Uyghur and Kazakh) and
      Vietnamese.

PMID- 30218176
TI  - Isolation and Complete Genome Sequence of a Novel Marinobacter Phage B23.
AB  - We used the double-agar layer method to isolate a novel Marinobacter marina
      bacteriophage, B23, from the surface water sample of the Bohai sea of China.
      There is some work to better understand the phage. The result of transmission
      electron microscopy revealed that B23 belongs to the family Siphoviridae with a
      head of 80 nm in diameter and a tail of 230 nm. Microbiological characterization
      evidenced that phage B23 is stable at the temperatures from - 25 to 60  degrees
      C, and showed vigorous vitality at pH between 4.0 and 12.0. One-step growth
      experiment showed that it had a longer latent period and higher lysis efficiency.
      Furthermore, the complete genome of B23 was sequenced and analyzed, which
      consists of a 35132 bp DNA with a G + C content of 59.8% and 50 putative open
      reading frames. The genome was divided into five parts, consisting of DNA
      replication and regulation, phage packaging, phage structure, host lysis and
      hypothetical protein.

PMID- 30218177
TI  - Ciclosporin and chorea: a new association?

PMID- 30218179
TI  - Spine challenges in mucopolysaccharidosis.
AB  - PURPOSE: Mucopolysaccharidosis (MPS) are rare inherited metabolic diseases,
      causing lysosomal storage of mucopolysaccharides; clinical presentation involves
      skeletal system and particularly the spine. Anomalies include developing kyphosis
      at thoracolumbar junction, that can causes nervous symptoms, and dens hypoplasia
      with associated atlantoaxial subluxation that can cause myelopathy. We present
      our experience in the treatment of spine pathology in MPS. METHODS: Medical
      treatments of MPS seem to have little impact on spine disease: treatment of
      cervical instability often includes surgical decompression and stabilization, as
      in patient MPS1 that we present, while thoracic lumbar kyphosis is treated by
      bracing and, in severe cases, with surgery. Bracing is more effective in kyphosis
      under 40 degrees  Cobb. Our surgical cases with thoracic lumbar kyphosis over 40
      degrees  Cobb, treatment include the first one ever described by only posterior
      approach with vertebrectomy in MPS and a case of lateral costo-transverse
      approach instrumented correction. RESULTS: Surgical patients had no major
      complications after surgery and CT scan at follow-up showed complete fusion
      without loss of correction, even if in a cervical case we used an adult rigid
      instrumentation in a four year-and-six month-old girl (11 years follow-up) and in
      thoracic lumbar kyphosis case treated by vertebrectomy due to diminutive anatomy
      we positioned interbody cage in suboptimal position. CONCLUSIONS: Bracing is a
      viable treatment strategy in thoracic lumbar kyphosis and can obtain good
      clinical results at medium terms follow-up even if kyphosis deformity remains in
      radiographs. Surgical treatment is effective in severe evolving cases both at
      cervical and thoracic lumbar level, main difficulties arose from unavailability
      of dedicated instrumentation in very young patient, as even smallest devices
      available are often too big.

PMID- 30218178
TI  - Ethical challenges in tracheostomy-assisted ventilation in amyotrophic lateral
      sclerosis.
AB  - The special nature of amyotrophic lateral sclerosis (ALS) and tracheostomy with
      invasive ventilation (TIV) leads to challenges that can be difficult in two
      senses: not only to handle well, but also to discuss with patients and other
      involved stakeholders. Because of the delicate nature of interpersonal relations
      and communication in ALS, some of the downsides to TIV may almost take on a
      nature of taboo, making them difficult to raise for open discussion. Yet these
      ethical challenges are important to be aware of, not only for health
      professionals and managers but, arguably, also for patients and next of kin. They
      are important also for a wider professional and societal debate about whether and
      to whom TIV should be offered. In this paper we highlight and examine ethical
      challenges in TIV for ALS, with a special emphasis on those that are hard to
      discuss openly and that therefore might fail to be addressed. The analysis is
      structured by the four core principles of healthcare ethics: beneficence,
      nonmaleficence, respect for patient autonomy, and justice.

PMID- 30218180
TI  - The effects of rotator cuff tear on shoulder proprioception.
AB  - PURPOSE: To evaluate the effects of rotator cuff tear (RCT) and its severity on
      shoulder proprioception. METHODS: We studied 132 consecutive patients (67 M-65 F;
      mean age +/- SD, 66.03 +/- 9.04; range, 43-78) who underwent arthroscopic rotator
      cuff repair. Tear size was determined intra-operatively. The control group
      included 82 subjects (38 M-44 F; mean age +/- SD, 65.87 +/- 8.06; range, 41-75)
      with no RCT. All participants, wearing an eye mask, were submitted to the
      evaluation of the joint position sense (JPS) at 30 degrees , 60 degrees , 90
      degrees , 120 degrees , and 150 degrees  of shoulder forward flexion during the
      sitting position, using a digital inclinometer securely attached to the subject's
      arm using hook-and-loop straps. The passive placement and active replacement
      method was used; the order of the tested angles was randomly selected. The entire
      test was repeated three times. The error score, by averaging the three trials,
      was measured as the absolute difference between the target angle and the observed
      angle. Statistics were performed. RESULTS: The intraclass correlation coefficient
      for all degrees of flexion movement measured was > 0.90, exhibiting a very high
      correlation. We found significant differences between cases and controls
      regarding the results of joint position sense error at all measurements (p <
      0.05). According to RCT size, we found significant differences between groups at
      30 degrees  (F = 27.27, p < 0.001), 90 degrees  (F = 5.37, p = 0.006), 120
      degrees  (F = 10.76, p < 0.001), and 150 degrees  (F = 30.93, p < 0.001) of
      shoulder flexion; in details, patients with massive RCT showed greater absolute
      error value than those with both small and large RCT at 30 degrees , 90 degrees ,
      120 degrees , and 150 degrees  of shoulder flexion (p < 0.05). CONCLUSIONS: RCT
      provokes an alteration of shoulder proprioception, evaluated as the loss of joint
      position sense, and the impairment is related to tear severity.

PMID- 30218181
TI  - Minimally invasive surgery for hallux valgus: a systematic review of current
      surgical techniques.
AB  - PURPOSE: The aim of this study was to systematically evaluate the available
      literature on minimally invasive surgical (MIS) treatment for hallux valgus and
      to provide an overview of the different surgical techniques. METHODS: A
      systematic review of the literature available in MEDLINE, EMBASE, and the
      Cochrane database was performed including studies from January 2001 to 1 January
      2018. The radiological outcomes (hallux valgus angle (HVA), intermetatarsal angle
      (IMA)), complication rates, and clinical outcome scores were evaluated. The
      MINORS scale was used to assess the methodological quality of included articles.
      RESULTS: Of 278 reviewed articles, 23 met the inclusion criteria. The included
      studies reported on the results of 2279 procedures in 1762 patients. The surgical
      techniques were divided into five categories: the Bosch technique, MIS Chevron
      Akin, Reverdin-Isham procedure, Endolog system, and techniques involving distal
      soft tissue release and fixation. Results regarding radiological correction,
      clinical outcomes, and complication rate varied widely. CONCLUSIONS: The studies
      included were of too little level of evidence to allow for data pooling or meta
      analysis. There were too few studies on each surgical technique category to
      assess whether one is more effective than the rest. However, there is some
      evidence that the Chevron and Akin showed the most potential for improvement of
      the HVA and the Endolog for the IMA. An overall complication rate of 13% was
      obtained among all included studies. Appropriately powered randomized controlled
      trials, utilizing validated outcome measures, blinded assessors, and long-term
      follow up are needed to assess the efficacy of MIS techniques.

PMID- 30218182
TI  - Acetabular reinforcement rings associated with allograft for severe acetabular
      defects.
AB  - Acetabular revisions with severe bone defects can be challenging procedures.
      Several grading systems have been set into place to help the surgeon adequately
      gauge the degree of bone loss within the acetabulum. Internationally innovative
      research in orthopedics and bio-engineering has helped with progression of
      successful techniques and rings to re-establish the normal anatomy of the hip.
      The purpose of this review is to evaluate the outcomes of the different
      acetabular reinforcement rings in the setting of severe acetabular defects. A
      successive report of relevant data from the literature of multiple techniques
      will be provided. The procedures include the cup-cage, the Muller ring, the Ganz
      Ring, the Kerboull acetabular reinforcement device (KARD), the graft augmentation
      prosthesis (GAP) ring, and the Burch-Schneider ring. The main focus of this
      overview is rings only; other devices such as trabecular augments, custom-made
      cages, or oblong cups are not discussed. Furthermore, a special emphasis on the
      surgical technique of the KARD is also given. Procedures using these rings are
      usually associated with bone grafts either bulk or morselized. When considering
      the available data on these various rings used for reconstruction of the severely
      damaged acetabulum, the cup-cage, the KARD, and the Burch-Schneider ring appear
      to be reliable options for more successful long-term outcomes.

PMID- 30218183
TI  - "U" route transforaminal percutaneous endoscopic thoracic discectomy as a new
      treatment for thoracic spinal stenosis.
AB  - PURPOSES: To describe the rationale, surgical technique, and short-term follow-up
      results of a new minimally invasive treatment for thoracic spinal stenosis (TSS)
      caused by herniation, ossification of the ligamentum flavum (OLF), and/or
      ossification of the posterior longitudinal ligament (OPLL) with a "U" route
      transforaminal percutaneous endoscopic thoracic discectomy (PETD). METHODS:
      Fourteen patients, including seven males and seven females, underwent "U" route
      PETD. Myelopathy was caused by OLF in 14 patients, OPLL in one, combined OLF-OPLL
      in ten, and intervertebral disc herniation (IDH) in five. Decompression was
      performed in one segment in 12 patients, and in two segments in two patients. The
      Japanese Orthopedic Association (JOA) scores, visual analog scale (VAS) scores,
      and complications were documented. RESULTS: The JOA scores improved from 4.64 +/-
      2.31 pre-operatively to 7.07 +/- 1.59 one day post-operatively and 11.79 +/- 1.85
      at final follow-up. The difference between pre-operation and post-operation was
      statistically significant (P < 0.05). Moreover, the VAS score was 6.07 +/- 2.06
      points pre-operatively, decreasing to 3.00 +/- 1.24 points at one day post
      operatively, and 1.14 +/- 0.86 points at last follow-up (P < 0.05). Dural tear
      was observed in two cases during the intervention. No patient had transient
      worsening of pre-operative paralysis. CONCLUSIONS: This retrospective analysis
      shows that "U" route PETD for decompression may be a feasible alternative to
      treat thoracic spinal stenosis.

PMID- 30218185
TI  - Predicting cervical intraepithelial neoplasia recurrence in HIV-infected and 
      noninfected women by detecting aberrant promoter methylation in the CDH1, TIMP3,
      and MGMT genes.
AB  - PURPOSE: Aberrant DNA methylation is present in virtually all types of human
      cancer. There is no clear evidence that methylation status can predict bad
      prognosis in patients with CIN recurrence in HIV infected. This study evaluates
      the relationship between aberrant methylation of CpG islands of CDH1, TIMP3 and
      MGMT genes and CIN recurrence in HIV-infected and -noninfected women. METHODS:
      This is a nested case-control study involving 33 cases with CIN recurrence and
      114 controls without recurrence, HIV infected and noninfected, treated with LEEP,
      between 1999 and 2004. Recurrence diagnosis was established after biopsy. Genes
      methylation profile was assessed by MSP-PCR technique in formalin-fixed, paraffin
      embedded cone specimens. Statistical analysis was performed to compare
      categorical variables, using chi2 test with Yates correction and Fisher's exact
      test. Multivariate analysis was carried out using logistic regression. RESULTS:
      CIN recurrence was more frequent in women with glandular involvement (OR 11.6;
      95% CI 2.93-45.89) and compromised surgical margins (OR 2.5; 95% CI 0.87-7.27) in
      the cervical cone and in HIV-infected women (OR 2.47; 95% CI 0.87-7.05). One
      methylated allele of CDH1, TIMP3 and MGMT genes was present in 87.9% women with
      CIN recurrence. Promoter hypermethylation of TIMP3 and MGMT was detected in women
      with CIN recurrence and without CIN recurrence independent of HIV infection with
      significant difference between groups (p = 0.04 and p = 0.02, respectively).
      CONCLUSIONS: CIN recurrence was associated with glandular involvement and
      compromised margins in cone biopsy and HIV infection. The presence of CpG islands
      hemimethylation in TIMP3 and MGMT genes is a promising triage method in CIN
      recurrence.

PMID- 30218184
TI  - Ovarian survival after pelvic radiation: transposition until the age of 35 years.
AB  - PURPOSE: To evaluate the effectiveness of ovarian transposition (OT) prior to
      radiation therapy (RT) and to evaluate the effect of age on ovarian survival (OS)
      after OT. METHODS: We performed a retrospective control study, with women (aged <
      45 years) who underwent OT prior to pelvic radiation, versus women diagnosed with
      cervical cancer and treated with hysterectomy/trachelectomy and radiation
      therapy. All women were treated between 1989 and 2010. The 5 years OS rate was
      calculated, with a sub-analysis for age (25-30; 31-35 and 36-40 years). Ovarian
      failure was defined as climacteric complaints (with or without starting hormone
      replacement therapy) and/or laboratory measurements (FSH > 40 IU/L and/or
      estradiol < 100 pmol/L), or bilateral salpingo oophorectomy. Women were censored
      at recurrence. RESULTS: Twenty-seven women after OT and 29 controls were
      included. The radiation dose was 44.8 Gy (25.0-63.0 Gy) and 46.3 Gy (45.0-50.0
      Gy), respectively. The 5-year ovarian survival rate was 60.3% versus controls 0%
      (p < 0.001 95% CI 3.48-11.50). Despite the decrease in ovarian survival after OT
      with increasing age, in all age groups (25-30, 30-35 and 35-40) ovarian survival
      after OT was significantly better compared to women without OT (p = 0.001; p =
      0.004 and p = 0.000, respectively). Neither intra-vaginal radiation therapy of
      concomitant chemotherapy in addition to pelvic radiation significantly altered
      ovarian survival. CONCLUSIONS: Our data shows that ovarian transposition prior to
      pelvic radiation is effective in women until the age of 35 years and needs to be
      discussed in patients aged 36-40 years.

PMID- 30218186
TI  - Termination of pregnancy following prenatally diagnosed central nervous system
      malformations.
AB  - PURPOSE: To analyze fetal cerebral malformations with late termination of
      pregnancy (TOP) and to evaluate the rate of cases that could have been detected
      earlier using international recommended requirements of sonographic examination
      of the fetal central nervous system (CNS). MATERIALS AND METHODS: Cases of
      singleton pregnancies above 18 + 0 weeks of gestation ending in late TOP due to
      fetal CNS malformations between 2002 and 2011 were retrospectively reviewed. The
      cases were divided into isolated and non-isolated cerebral malformations.
      Prevalence and timing of TOP were assessed relative to the identified
      malformations. RESULTS: During this 10-year period, 212 (20.8%) out of 1017 late
      TOPs were performed in pregnancies with fetal cerebral malformations. 59 cases
      were excluded because of chromosomal anomalies. 86 (56.2%) of the remaining 153
      cases were isolated cerebral malformations while 67 (43.8%) were non-isolated.
      TOP after viability (>= 24 + 0 weeks of gestation) was performed in 61.4%
      (94/153). Substantial morbidity (n = 80; 52.3%) and mental retardation (n = 33,
      38.4%) made up the leading prognostic groups. In about 80% of detectable
      anomalies, diagnosis of CNS malformation could have been made earlier by
      following international guidelines of fetal CNS examination at second trimester
      scan. CONCLUSION: General implementation of ultrasound screening in maternity
      care can significantly reduce the number of late TOPs in Germany.

PMID- 30218187
TI  - Modeling symptom drivers of oral intake in long-term head and neck cancer
      survivors.
AB  - PURPOSE: This study examined the relationship between self-reported symptom
      severity and oral intake in long-term head and neck cancer (HNC) survivors.
      METHODS: An observational survey study with retrospective chart abstraction was
      conducted. HNC patients who had completed an MD Anderson Symptom Inventory-Head
      and Neck (MDASI-HN) questionnaire and also had clinician graded oral intake
      ratings (Functional Oral Intake Scale [FOIS]) were included. Correlation
      coefficients were computed. FOIS scores were regressed on MDASI-HN symptom items
      using stepwise backwards elimination for multivariate models. RESULTS: One
      hundred and fifty-two survey pairings were included in the analysis (median 44
      months follow-up, range 7-198). Per FOIS, 28% of survivors maintained a total
      oral diet with no restrictions, 67% reported a restricted oral diet (without
      tube), 3% were partially tube-dependent with some oral intake, and 2% were NPO.
      Of the 22 symptom items, the most severe items in decreasing order were dry
      mouth, difficulty swallowing?chewing, problems with mucus, tasting food, and
      choking/coughing. Significant bivariate correlations, after Bonferroni correction
      for multiple comparisons, were present for 8 of 22 symptoms with FOIS. On
      multivariate analysis, symptom severity for difficulty swallowing and problems
      with teeth/gums remained significantly associated with FOIS. CONCLUSIONS: Oral
      intake in HNC survivorship is a multidimensional issue and functional outcome
      that is impacted not only by dysphagia but also by dental status. Symptom drivers
      of oral intake likely differ in acute survivorship. Nonetheless, these findings
      highlight the lack of specificity in this end point and also the need for
      multidisciplinary supportive care to optimize oral intake in survivors.

PMID- 30218188
TI  - Efficacy and safety of Viscum album extract (Helixor-M) to treat malignant
      pleural effusion in patients with lung cancer.
AB  - PURPOSE: Manifestations of malignant pleural effusions (MPEs) are alleviated by
      local therapies as well as by systemic treatment. After 2009, when commercial use
      of talc was discontinued in Korea, we have used Helixor-M, which is derived from
      the European mistletoe (Viscum album), as an alternative sclerosing agent for
      pleurodesis. We aimed to evaluate the efficacy and safety of Helixor-M for
      controlling MPE. METHODS: Between 2009 and 2015, we consecutively enrolled 52
      patients with lung cancer, who underwent pleurodesis to treat MPE and were
      analyzed retrospectively. On day 1, 100 mg of Helixor-M was instilled via pleural
      catheter. If the procedure was not effective, it was repeated every other day up
      to five times, and the dose increased each time by 100 mg. The primary study
      outcome was reappearance of pleural effusion at 1 month after the last
      pleurodesis procedure. RESULTS: The median age of patient was 63 years, and 77%
      of the 52 patients were male. About 85% of pleural effusions were found to be
      malignant by cytogenetic analysis. Forty-two (81%) patients were evaluable for
      recurrence of MPE. The 1-month recurrence rate was 48% (20/42). Among the 20
      patients who developed recurrent MPE, 6 required therapeutic thoracentesis.
      Thirteen (25%) patients experienced procedure-related pain requiring medication.
      Eight (15%) had fever > 38  degrees C. CONCLUSIONS: Our results suggest that a
      pleurodesis with Helixor-M was an effective and tolerable procedure for
      controlling MPE in lung cancer patients.

PMID- 30218189
TI  - One-minute time interval estimation as a novel ultrashort tool for distress
      screening.
AB  - PURPOSE: Our study explores the potential relationship between time estimation
      and level of distress in cancer patients prior to starting chemotherapy. METHODS:
      Time estimation was assessed in 262 chemonaive patients with solid tumors by
      evaluating each subject's prospective estimation of how fast 1 min passed
      compared to the actual time. The median value (40 s) of time estimation was used
      to stratify the patients into two categories of fast and slow time estimation.
      The National Comprehensive Cancer Network Distress Thermometer was used at the
      beginning of treatment to evaluate levels of distress. Patients scoring 4 or
      above (51.9%) were regarded as having high levels of distress. RESULTS: The
      pattern of the time estimation distributions significantly changed according to
      the level of distress. Patients with a fast time estimation had significantly
      higher levels of distress (4.55 +/- 3.1) than patients with a slow time
      estimation (3.3 +/- 2.9) (p = 0.001). ROC analysis revealed that at the optimal
      cutoff value of time estimation, patients with low and high distress levels can
      be discriminated with an AUC = 0.60 (95% CI: 0.53-0.67, p = 0.005) and with a
      sensitivity of 62.5% and specificity of 53.2%. Moreover, in a multivariate
      logistic regression model, fast time estimation was an independent predictor of
      high levels of distress. CONCLUSION: Time estimation is a novel potent indicator
      of high levels of distress in cancer patients. This test is an easily performed,
      time-saving, and nonintrusive ultrashort screening tool that is even suitable for
      patients who are not willing to reveal their level of distress via direct
      questionnaires.

PMID- 30218190
TI  - Long-term renal follow-up of children treated with cisplatin, carboplatin, or
      ifosfamide: a pilot study.
AB  - BACKGROUND: Childhood cancer survivors treated with cisplatin, ifosfamide, or
      carboplatin are at risk for late kidney and blood pressure (BP) abnormalities.
      Few studies have comprehensively evaluated kidney outcomes and 24-h ambulatory BP
      monitoring (ABPM) in this population. We aimed to describe chemotherapy
      associated acute kidney injury (AKI) and late kidney outcomes using standardized
      definitions. METHODS: This was a single-center longitudinal pilot study of 23
      children who participated in a previous study during cisplatin, carboplatin, or
      ifosfamide treatment. Medical charts were reviewed retrospectively. Available
      patients were approached for a study visit for blood and urine collection, BP
      measurement, and ABPM. AKI is defined by serum creatinine (SCr) rise (Kidney
      Disease: Improving Global Outcomes definition [SCr-AKI]). Electrolyte-AKI is
      defined by hypokalemia, hypophosphatemia, or hypomagnesemia. Chronic kidney
      disease (CKD) is defined by estimated glomerular filtration rate < 90 mL/min/1.73
      m2, albuminuria, or proteinuria. Electrolyte-CKD is defined by low serum
      electrolyte concentration or electrolyte supplementation. RESULTS: Median age at
      chemotherapy start was 8.3 years; 9/23 (39%) were boys. Fourteen out of 23 (61%)
      patients had SCr-AKI during therapy; all developed electrolyte-AKI. Median 5.7
      years post-chemotherapy, 7/22 (32%) had CKD, 11/23 (48%) had electrolyte-CKD, and
      2/20 (10%) had hypertension. Fifteen out of 23 patients (65%) had either CKD,
      electrolyte-CKD, or hypertension. In ten patients available for a study visit
      (median 4.9 years post-chemotherapy), 1/10 (10%) had hypertension by ABPM; none
      had masked or white coat hypertension. All ten had at least one kidney
      abnormality (CKD, electrolyte-CKD, office pre-hypertension, or abnormal ABPM).
      CONCLUSIONS: Using standardized outcome definitions, children treated with
      cisplatin, carboplatin, or ifosfamide have a high prevalence of late kidney
      abnormalities. Research must elucidate best practice for post-cancer treatment
      follow-up and kidney complication treatment.

PMID- 30218191
TI  - An update on LDL apheresis for nephrotic syndrome.
AB  - Low-density lipoprotein (LDL) apheresis has been used increasingly in clinical
      practice for the treatment of renal diseases with nephrotic syndrome (NS),
      specifically focal segmental glomerulosclerosis (FSGS). Persistent hyperlipidemia
      for prolonged periods is nephrotoxic and leads to chronic progressive glomerular
      and tubulointerstitial injury. Effective management of hyperlipidemia with HMG
      CoA reductase inhibitors or LDL apheresis in drug-resistant NS patients may
      prevent the progression of renal disease and, in some patients, resolution of NS
      symptoms. Available literature reveals beneficial effects of LDL apheresis for NS
      refractory to drug therapy. Here we update on the current understanding of lipid
      nephrotoxicity and application of LDL apheresis to prevent progression of renal
      diseases.

PMID- 30218192
TI  - Small-incision cholecystectomy (through a cylinder retractor) under local
      anaesthesia and sedation: a prospective observational study of five hundred
      consecutive cases.
AB  - BACKGROUND: Transcylindrical cholecystectomy (TC) can be performed under local
      anaesthesia and sedation (LAS) in ambulatory surgery (AS). The aim of this study
      was to assess the feasibility and results of TC under LAS. METHODS: TC under LAS
      was proposed to 583 consecutive patients with cholelithiasis in an AS unit. For
      the TC procedure, a cylindrical retractor with a transparent plunger was inserted
      into the hepatocystic triangle, and cholecystectomy was performed through the
      retractor with reusable open instruments. Pre-, intra-, and post-operative
      variables were prospectively registered, including complications, reasons for
      conversion to general anaesthesia (GA), non-programmed admissions, readmissions,
      pain assessments, and satisfaction with the procedure. RESULTS: Five hundred
      patients were eligible for LAS, with GA being required in 128 (25.6%) of them. AS
      was programmed for 447 patients. The rates of non-programmed admissions,
      readmissions, and conversion to laparotomy were 8.7% (39), 0.8% (4), and 2.6%
      (13), respectively. There was no main bile duct injury. At 24 h, physical status
      was good or excellent in 80.4% of the patients. A history of acute cholecystitis,
      male sex, a body mass index (BMI) >= 39.5 kg/m2, and non-suspected acute
      cholecystitis were found to be independent variables associated with conversion
      to GA. CONCLUSIONS: TC under LAS is a safe procedure in AS and is feasible in 74%
      of cholelithiasis patients. Male sex, BMI, gallbladder wall thickness, and a
      history of acute cholecystitis are factors that increase the probability of
      conversion to GA. This prospective study was approved by the ethics committee of
      Badajoz for patient protection for biomedical research and has been
      retrospectively registered under the research registry UIN: researchregistry3979.

PMID- 30218194
TI  - The St. Gallen International Expert Consensus Conference on the Primary Therapy
      of Early Breast Cancer 2017: Egyptian view.
AB  - PURPOSE: The theme of the 15th St. Gallen International Breast Cancer Conference
      2017 in Vienna, Austria was about seeking where appropriate to escalate or de
      escalate therapies for early breast cancer based on the up-to-date information of
      loco-regional and systemic therapies. Along with this line, a group of Egyptian
      experts decided to arrange for a consensus session to elicit the differences and
      similarities in therapy recommendations for early breast cancer in Egypt compared
      to the original Saint Gallen voting and recommendations. METHODS: During the
      Egyptian National Cancer Institute's Annual Congress held in November 2017, 30
      Egyptian scientists and clinicians from different specialties gathered in a
      special session and voted on the same questions of the original 15th St. Gallen
      consensus. Therapies were discussed from different aspects including their
      intensity, duration, and side effects, and were correlated with tumor stage and
      tumor biology. RESULTS AND CONCLUSIONS: This report summarizes the voting
      questions and resulting percentages of answers of the Egyptian scientists.
      Interestingly the differences were minimal between the Cairo and original Saint
      Gallen Consensus denoting a more global view of breast cancer management all over
      the world.

PMID- 30218193
TI  - Prognostic factors for actual long-term survival in the era of multidisciplinary
      treatment for pancreatic ductal adenocarcinoma.
AB  - PURPOSE: Recent advances in multidisciplinary treatments are improving the
      postoperative prognosis of pancreatic ductal adenocarcinoma (PDAC). However, the
      prognosis even after potentially curative resection remains poor. The aim of this
      study was to identify the clinical and pathological features of actual 5-year
      survivors under current circumstances. METHODS: A total of 128 patients who
      underwent pancreatectomy for PDAC at our institution between January 2006 and
      December 2011 were retrospectively analyzed. RESULTS: The actual 5-year overall
      survival rate for all patients was 30.9%, with a median survival time of 33.1
      months. Of 128 patients, 25 (19.5%) survived for 5 years after surgery without
      disease recurrence. A univariate analysis showed that the pretreatment serum CA19
      9 value, tumor depth, lymph node metastasis, and UICC stage at resection were
      significant predictive factors for the actual long-term survival. A multivariate
      analysis showed that a pretreatment serum CA19-9 value >= 110 U/mL was a
      significant unfavorable prognostic indicator. In addition, all subjects in the 5
      year survival group completed adjuvant chemotherapy. The recurrence rate in the
      liver was significantly lower and that in the lung significantly higher in the
      long-term survival group than in the short-term survival group. CONCLUSIONS: The
      factors contributing to the long-term survival of PDAC were the pretreatment CA19
      9 value and the completion of adjuvant chemotherapy. To achieve the actual long
      term survival and cure after pancreatectomy for pancreatic cancer, further
      treatment strategies enhancing the completion rate of adjuvant chemotherapy are
      required.

PMID- 30218195
TI  - Only estrogen receptor "positive" is not enough to predict the prognosis of
      breast cancer.
AB  - PURPOSE: Beginning in 2018, biomarkers including estrogen receptor (ER) status
      were incorporated in the 8th AJCC staging system. ER expression levels were not
      considered in these changes. We hypothesized that the levels of ER expression
      could affect the prognosis of breast cancer. METHODS: A retrospective review was
      conducted to identify all female patients with invasive breast cancer between
      2003 and 2012. ER negative (group I), weakly ER-positive (group II), and strongly
      ER-positive (group III) were defined as Allred total scores of 0-2, 3-5, and 6-8,
      respectively. We examined a multigene panel, designated the BCT score, which is a
      newly developed prognostic model for predicting the risk of a distant metastasis.
      RESULTS: Among the 4949 patients enrolled in this study, 1310 (26.5%), 361
      (7.3%), and 3277 (66.2%) were categorized as group I, II, and III, respectively.
      Median F/U duration was 57.8 months. Compared to group III, patients in group II
      were younger, had larger tumors, and were also more likely to have PR-negative
      tumors, HER-2 amplification, high Ki-67, and high nuclear grade. Between group II
      and III, there was a significant difference in OS (P = 0.0764, 0.909, and 0.010,
      respectively). After adjusting for additional factors that may affect OS, the HR
      for OS showed higher in group II than in group III. The baseline median BCT score
      indicated that lower ER expression was associated with significantly higher BCT
      score (P < 0.0001) and significantly more likely to have high risk group (P <
      0.0001) relative to higher levels of ER expression group. CONCLUSION: ER
      expression levels affect the prognosis of breast cancer. The risk for patients
      with weakly ER-positive breast cancer should not be underestimated.

PMID- 30218196
TI  - Supplementation Adherence and Outcomes Among Pregnant Women After Bariatric
      Surgery.
AB  - PURPOSE: Most patients undergoing bariatric surgery (BS) are fertile women whose
      postoperative (post-op) hormonal balance and weight loss increases fertility,
      frequently leading to pregnancy. This study aims to analyze supplementation
      adherence of pregnant women after BS and perinatal outcomes. MATERIALS AND
      METHODS: This retrospective study analyzed records from women after BS who
      consulted nutritionists at least twice during pregnancy. Each patient received
      nutritional guidance about vitamin and mineral supplementation and protein
      intake. Demographic data, body mass index (BMI), percentage of weight loss (%WL)
      at conception, maximum post-op BMI and %WL, post-op time at conception,
      supplementation adherence, biochemical data, possible gestational complications,
      and infant's birth weight were collected. RESULTS: Data was obtained from 23
      women (mean age 33 +/- 4 years). On average, patients became pregnant 43 months
      after surgery. The mean preoperative BMI was 40.2 kg/m2, the maximum post-op %WL
      was 36.6%, and the mean %WL at conception was 32.0%. No gestational intercurrence
      was related to biochemical data. Supplementation adherence was 34.7% for one
      multivitamin and 34.7% for two multivitamins; 43.5% for iron, 43.5% for omega 3,
      39.1% for folic acid, 17.4% for B complex, and 60.8% for calcium. Mean infant
      birth weight was 3.0 kg, and it was not associated with maximum %WL, % WL at
      conception, and time since BS at conception. CONCLUSION: Our data indicate
      satisfactory adherence to post-op micronutrient supplementation and few
      gestational complications following BS. Moreover, child's birth weight was not
      associated with maximum %WL, %WL at conception, or time since BS.

PMID- 30218197
TI  - Model of calculating a composite environmental index for assessing the impact of
      port processes on environment: a case study of container terminal.
AB  - Environmental standards are not harmonized in ports and neither are the
      instruments used for the assessing the condition of environmental efficiency of a
      port system. The purpose of the research conducted in the framework of this paper
      is to propose the methodology for calculating the Port Environmental Index (IE)
      which synthesizes all environmental aspects of port operations into a single
      value. The goals of the paper were the following: (1) to integrate the relevant
      environmental aspects of port activities and evaluate the impact of port terminal
      processes on the environment by calculating the IE and (2) to validate the index
      by applying it to a container terminal in the north-western part of Croatia. IE
      was constructed using the compound index method where compilation and aggregation
      of individual indicators were used to form a compound index of the overall effect
      of port processes on the environment. The validation of IE by applying it to a
      container terminal (Port of Rijeka, north-western part of Croatia) showed that
      the IE can be easily applied and its application allows monitoring the overall
      changes in environmental performance of port areas. In addition, IE can be used
      to test different pollution abatement strategies including testing interventions
      in the port processes and determining their share in the overall impact on the
      environment. In addition, the potential constraints to using such an approach are
      discussed in the paper.

PMID- 30218198
TI  - Weak interactions in furan dimers.
AB  - Dimers of furan, 2,3-dihydrofuran, 2,5-dihydrofuran and tetrahydrofuran were
      investigated with the use of theoretical methods to determine the interactions
      that keep the molecules together. The QTAIM and NCI methods confirmed that for
      furan dimers the C-H?O hydrogen bond and stacking interactions can form the
      dimers with similar energy. For 2,3-dihydrofuran, 2,5-dihydrofuran and
      tetrahydrofuran, the decisive mechanism of dimer formation is the stacking
      interaction between the furan rings.

PMID- 30218199
TI  - Calculate protein-ligand binding affinities with the extended linear interaction
      energy method: application on the Cathepsin S set in the D3R Grand Challenge 3.
AB  - We participated in the Cathepsin S (CatS) sub-challenge of the Drug Design Data
      Resource (D3R) Grand Challenge 3 (GC3) in 2017 to blindly predict the binding
      poses of 24 CatS-bound ligands, the binding affinity ranking of 136 ligands, and
      the binding free energies of a subset of 33 ligands in Stage 1A and Stage 2. Our
      submitted predictions ranked relatively well compared to the submissions from
      other participants. Here we present our methodologies used in the challenge. For
      the binding pose prediction, we employed the Glide module in the Schrodinger
      Suite 2017 and AutoDock Vina. For the binding affinity/free energy prediction, we
      carried out molecular dynamics simulations of the complexes in explicit water
      solvent with counter ions, and then estimated the binding free energies with our
      newly developed model of extended linear interaction energy (ELIE), which is
      inspired by two other popular end-point approaches: the linear interaction energy
      (LIE) method, and the molecular mechanics with Poisson-Boltzmann surface area
      solvation method (MM/PBSA). Our studies suggest that ELIE is a good trade-off
      between efficiency and accuracy, and it is appropriate for filling the gap
      between the high-throughput docking and scoring methods and the rigorous but much
      more computationally demanding methods like free energy perturbation (FEP) or
      thermodynamics integration (TI) in computer-aided drug design (CADD) projects.

PMID- 30218200
TI  - [Progressive respiratory failure and weakness in a 61-year-old woman].
AB  - A 61-year-old woman was admitted with a suspected diagnosis of atypical
      pneumonia. Extended diagnostic measures revealed interstitial lung disease (ILD),
      polyserositis, polyarthritis and myopathy. With detection of an antibody against
      PL-7 (anti-threonyl-transfer-RNA synthetase) the diagnosis of anti-synthetase
      syndrome (ASS) was established. ASS are rare inflammatory myopathies which
      frequently present as multisystemic diseases with severe organ involvement. An
      immunosuppressive regimen with steroids and cyclophosphamide led to successful
      induction of disease remission. Maintenance therapy will be conducted with
      azathioprine. ASS should always be considered in the differential diagnosis of
      myopathies and ILDs.

PMID- 30218201
TI  - [The 2017/2018 influenza season-business as usual? : A statement of medical
      societies].

PMID- 30218202
TI  - A new combination for the determination of ultratrace cadmium: solid-phase
      microextraction by stearic acid-coated magnetic nanoparticles prior to batch-type
      hydride generation atomic absorption spectrometry.
AB  - Solid-phase microextraction method based on stearic acid-coated magnetic
      nanoparticle has been combined with batch-type hydride generation atomic
      absorption spectrometry (BT-HGAAS) system to determine cadmium at ultratrace
      levels. After the adsorption of cadmium ions onto stearic acid-coated magnetic
      nanoparticles, they were easily separated from the aqueous phase by means of a
      magnet. All the instrumental and experimental parameters such as pH of buffer
      solution, interaction period, concentration, and volume of NaBH4 were optimized.
      Under the optimal conditions, limit of quantification (LOQ) and limit of
      detection (LOD) for the solid-phase microextraction (SPME) based on stearic acid
      coated magnetic nanoparticles-BT-HGAAS (SACMNP-BT-HGAAS) method were obtained as
      270.8 ng/L and 81.7 ng/L, respectively. The matrix-matching calibration method
      was performed in order to improve the accuracy of cadmium quantification in tap
      water and the recovery results obtained were as follows: 88.56 +/- 8.92 and 97.43
      +/- 9.76, for 6.0 and 8.0 ng/mL of cadmium-spiked tap water samples,
      respectively. Graphical abstract ?.

PMID- 30218203
TI  - Impact of high altitude on key determinants of female reproductive health: a
      review.
AB  - Imperishable research work was done on females visiting high-altitude (HA) areas
      for recreational activities or job purposes as well as on female HA natives.
      Hypoxia at HA is an unavoidable condition that affects the determinants of female
      reproductive functions like, the age of menarche and menopause, whole
      reproductive span, hormone synthesis, and fertility. This review will emphasize
      whether HA hypoxia is a threat to women: residents or visitors by analyzing these
      proximate determinants. Delayed menarcheal and advanced menopausal age was found
      to shorten the reproductive span in some HA populations, whereas in some cases,
      menstrual cycle was also reported to be irregular. In addition, the completed
      fertility rate (CFR) was increased when people migrated to lower altitude.
      Altered stress hormones and reproductive hormones were observed in sea-level
      females exposed to HA. Oxidative stress (OS) at HA was also reviewed to explain
      the probable reasons for the observed changes in these determinants because
      disturbed redox homeostasis may be a connecting link, affecting the reproductive
      functions. In conclusion, HA hypoxia plays a crucial role on various determinants
      of female reproductive health and this review will be helpful for more precise
      study along with the probable underlying mechanisms responsible for the changes
      in female reproductive functions at HA.

PMID- 30218204
TI  - Can molecular and atomic descriptors predict the electrophilicity of Michael
      acceptors?
AB  - In this paper, we assess the ability of various intrinsic molecular and atomic
      descriptors, grounded in the conceptual density functional theory and the quantum
      theory of atoms-in-molecules frameworks, to predict the electrophilicity of
      Michael acceptors, which are fundamental organic reagents involved in the
      formation of carbon-carbon bonds. To this aim, linear and multilinear regressions
      between these theoretical properties and the experimental values gathered in Mayr
      Patz' scale were performed. The relevance of quantum chemical descriptors are
      then discussed.

PMID- 30218205
TI  - In Vitro Validation of 4D Flow MRI for Local Pulse Wave Velocity Estimation.
AB  - PURPOSE: Arterial stiffness has predictive value for cardiovascular disease
      (CVD). Local artery stiffness can provide insight on CVD pathology and may be
      useful for diagnosis and prognosis. However, current methods are invasive,
      require real-time expertise for measurement, or are limited by arterial region.
      4D Flow MRI can non-invasively measure local stiffness by estimating local pulse
      wave velocity (PWV). This technique can be applied to vascular regions,
      previously accessible only by invasive stiffness measurement methods. MRI PWV
      data can also be analyzed post-exam. However, 4D Flow MRI requires validation
      before it is used in vivo to measure local PWV. METHODS: PWV, calculated from 4D
      Flow MRI and a benchtop experiment, was compared with petersons elastic modulus
      (PEM) of in vitro models. PEM was calculated using high-speed camera images and
      pressure transducers. Three transit-time algorithms were analyzed for PWV
      measurement accuracy and precision. RESULTS: PWV from 4D Flow MRI and reference
      benchtop experiments show strong correlation with PEM (R2 = 0.99). The cross
      correlation transit-time algorithm showed the lowest percent difference between
      4D Flow MRI and benchtop experiments (4-7%), and the point to point of 50%
      upstroke algorithm had the highest transit-time vs. distance data average R2
      (0.845). CONCLUSION: 4D Flow MRI is a feasible method for estimating local PWV in
      simple in vitro models and is a viable tool for clinical analysis. In addition,
      choice in transit-time algorithm depends on flow waveform shape and arterial
      region. This study strengthens the validity of 4D Flow MRI local PWV measurement
      in simple models. However, this technique requires validation in more complex
      models before it is used in vivo.

PMID- 30218206
TI  - A Hybrid Algorithm for Prediction of Varying Heart Rate Motion in Computer
      Assisted Beating Heart Surgery.
AB  - An essential requirement for performing robotic assisted surgery on a freely
      beating heart is a prediction algorithm which can estimate the future trajectory
      of the heart in the varying heart rate (HR) conditions of real surgery with a
      high accuracy. In this study, a hybrid amplitude modulation- (AM) and
      autoregressive- (AR) based algorithm was developed to enable estimating the
      global and local oscillations of the beating heart, raised from its major and
      minor physiological activities. The AM model was equipped with an estimator of
      the heartbeat frequency to compensate for the HR variations. The RMS of the
      prediction errors of the hybrid algorithm was in the range of 165-361 MUm for the
      varying HR motion, 21% less than that of the single AM model. With the capability
      of providing highly accurate predictions in a wide range of HR variation, the
      hybrid model is promising for practical use in robotic assisted beating heart
      surgery.

PMID- 30218207
TI  - Cynaropicrin from Cynara scolymus L. suppresses Porphyromonas gingivalis LPS
      induced production of inflammatory cytokines in human gingival fibroblasts and
      RANKL-induced osteoclast differentiation in RAW264.7 cells.
AB  - Periodontal diseases are a major public health problem affecting over half of the
      adult population worldwide. Lipopolysaccharide (LPS) produced by the
      periodontopathic bacterium Porphyromonas gingivalis induces the expression of
      inflammatory cytokines that promote inflammatory bone destruction. Mounting
      evidence supports that periodontal diseases are involved in the onset and
      progression of several systemic diseases, such as aspiration pneumonia and
      diabetes. Although treatment of periodontal diseases by removing the
      periodontopathic bacteria by brushing is a standard practice, it has limitations
      and is not effective in all cases. Therefore, a new method to replace or
      complement brushing is needed for the treatment of periodontal diseases. In this
      study, we investigated the anti-inflammatory effects of an extract from Cynara
      scolymus L. and its pharmacologically effective compound cynaropicrin, a
      sesquiterpene lactone, on human gingival fibroblasts (HGFs) stimulated by LPS and
      the potential anti-osteoclastogenic effects on RAW264.7 cells induced by receptor
      activator of NF-kappaB ligand (RANKL). We found that cynaropicrin inhibited IL-8
      and IL-6 mRNA and protein synthesis in LPS-stimulated HGFs in a dose-dependent
      manner. P. gingivalis LPS-induced degradation of IkappaBalpha and phosphorylation
      of NF-kappaB p65 were also suppressed by cynaropicrin, as was LPS-stimulated NF
      kappaB transactivation. Thus, cynaropicrin's inhibition of P. gingivalis LPS
      induced IL-8 and IL-6 expression may be due to the inhibition of the NF-kappaB
      pathway. Furthermore, we showed that cynaropicrin dramatically reduced RANKL
      induced osteoclast differentiation. These results suggest that cynaropicrin may
      be useful for preventing periodontal diseases and could prove valuable in the
      development of more effective preventative approaches for periodontal diseases.

PMID- 30218208
TI  - Aloin promotes osteogenesis of bone-marrow-derived mesenchymal stem cells via the
      ERK1/2-dependent Runx2 signaling pathway.
AB  - Osteoporosis is characterized by low bone mass and the degeneration of bone
      structure, conditions which increase the risk of fracture. Aloin has been shown
      to affect bone metabolism, but its role in osteogenic differentiation of bone
      marrow-derived mesenchymal stem cells (BMSCs) remains unclear. The aim of our
      study was to determine whether aloin promotes the proliferation and osteogenic
      differentiation of BMSCs and, if so, whether it acts via activation of the ERK1/2
      Runx2 signaling pathway. We found that the different concentrations of aloin
      tested had no obvious cytotoxic effects on the viability of BMSCs. Under
      osteogenic induction conditions, aloin increased cellular alkaline phosphatase
      activity, promoted BMSC mineralization, and increased osteogenic-related gene
      expression. In addition, treating the BMSCs with the signal transduction
      inhibitor PD98059 (ERK1/2) effectively attenuated Runx2 activation in these cells
      and also suppressed osteoblastic differentiation. Overall, our study demonstrates
      that aloin promotes osteogenic differentiation of BMSCs through activation of the
      ERK1/2-Runx2 signaling pathway.

PMID- 30218209
TI  - Treatment of coronary malperfusion in type A acute aortic dissection.
AB  - Coronary malperfusion is one of the most dreadful complications of acute aortic
      dissection because it causes catastrophic acute myocardial infarction in patients
      who are already severely ill. Our strategy was as follows. After the
      administration of heparin, emergency percutaneous coronary intervention (PCI) was
      urgently performed at the same time as starting to prepare the operating room. A
      stent was then placed to cover the full length of dissected coronary artery.
      Patients whose cardiac function improved after successful coronary artery
      reperfusion were transferred to the operating room to undergo central repair
      surgery. If the cardiac function did not recover even after coronary reperfusion,
      and the patient required extracorporeal membrane oxygenation, we considered the
      best supportive care without performing central repair surgery. In patients with
      left coronary malperfusion, we believe that preoperative PCI must be performed
      immediately. Preoperative PCI might delay central repair surgery and potentially
      increase the risk of catastrophic cardiac tamponade. However, the benefit of PCI
      in preserving cardiac function exceeds the risk of cardiac tamponade. The
      indications of PCI before central repair in patients with right coronary
      malperfusion should be considered after assessing each patient's condition,
      including the presence or absence of cardiac tamponade and right ventricular
      infarction, left ventricular function, the immediate availability of
      cardiologists or cardiac surgeons, and the speed of preparing the operating room.

PMID- 30218210
TI  - Stabilized red soil-an efficient liner system for landfills containing hazardous
      materials.
AB  - In recent decades, disposal of hazardous material has become a challenging task
      especially in case of landfills where leaching out of waste is possible. In such
      cases, an efficient and economical liner system using locally available material
      is very essential. In this paper, an attempt has been made to study the
      suitability of red soil stabilized using lime and Prosopis juliflora fibers as
      liner material for landfills. Prosopis is a woody weed available abundantly in
      tropical and subtropical regions of the world. The fibers were used at 0.0%,
      0.25%, 0.50%, 0.75%, and 1.0% by weight of the soil and the amount of lime used
      was kept constant as 4%. Tests results revealed decrease in plasticity index,
      increase in UCC strength, ductile behavior, decrease in consolidation settlement,
      reduction in permeability and shrinkage, and increase in CBR resistance in soils
      treated with both lime and Prosopis fibers. SEM images of stabilized soil
      revealed adherence of hydrated products of lime on the fiber surface, which
      facilitate efficient stress transfer between the soil and fibers. A single
      composite liner system was modeled using Visual MODFLOW by replacing the
      compacted clay layer with the stabilized red soil below the HDPE liner and the
      model was simulated. The simulation result showed that the performance of liner
      system with stabilized red soil is good and could prevent the aquifer from
      contamination. From the study, it can be concluded that stabilized red soil
      possesses the geotechnical properties required for an efficient liner system.

PMID- 30218211
TI  - Correction to: Measuring quality of life in children with spinal muscular
      atrophy: a systematic literature review.
AB  - In the original publication of the article, the co-author name "Stefan Boes" has
      been mistakenly missed out. This has been updated in this correction.

PMID- 30218212
TI  - IgA nephropathy: clearance kinetics of IgA-containing immune complexes.
AB  - IgA nephropathy (IgAN) is associated predominantly IgA deposition in the affected
      glomeruli and has been shown to be the most common glomerular disorder among
      young people in the world. Although the exact pathogenic mechanism underlying
      IgAN remains largely unknown, circulating IgA-containing immune complexes (IgA
      ICs) is considered to play a major role in initiating the development and
      evolution of the renal disorder. In this review article, we discuss the
      fundamental mechanisms of clearance kinetics of IgA ICs and related issues,
      covering the following: (1) role of circulating IgA ICs in the pathogenesis of
      IgAN and (2) elimination of IgA ICs from the body, with emphasis of the role of
      the liver and Fc receptors in immune cells.

PMID- 30218213
TI  - SPRINT and the Kidney: What Have We Learned?
AB  - PURPOSE OF REVIEW: To review the impact of the Systolic Blood Pressure
      Interventional Trial (SPRINT) on renal function and chronic kidney disease.
      RECENT FINDINGS: Hypertension is a risk factor for cardiovascular and kidney
      outcomes in patients with chronic kidney disease (CKD). The benefits of intensive
      blood pressure lowering in the CKD population in previous studies are unclear.
      The SPRINT compared standard (< 140 mmHg) and intensive (< 120 mmHg) blood
      pressure management in nondiabetic patients with high risk of cardiovascular
      disease. In the subgroup of patients with CKD, the most important finding was
      that intensive blood pressure lowering is associated with lower risk of
      cardiovascular disease and mortality. Other than lower levels of albuminuria,
      there was no benefit on clinical kidney outcomes with the intensive treatment
      group. The risk of incident CKD and episodes of acute kidney injury was higher in
      patients in the intensive treatment group, though most patients with acute kidney
      injury recovered kidney function. While the benefit of intensive blood pressure
      lowering on cardiovascular events and mortality with intensive blood pressure
      lowering is clear in patients with CKD, longer term follow-up may be needed to
      fully understand the effect on kidney function.

PMID- 30218214
TI  - Automatic Removal of False Connections in Diffusion MRI Tractography Using
      Topology-Informed Pruning (TIP).
AB  - Diffusion MRI fiber tracking provides a non-invasive method for mapping the
      trajectories of human brain connections, but its false connection problem has
      been a major challenge. This study introduces topology-informed pruning (TIP), a
      method that automatically identifies singular tracts and eliminates them to
      improve the tracking accuracy. The accuracy of the tractography with and without
      TIP was evaluated by a team of 6 neuroanatomists in a blinded setting to examine
      whether TIP could improve the accuracy. The results showed that TIP improved the
      tracking accuracy by 11.93% in the single-shell scheme and by 3.47% in the grid
      scheme. The improvement is significantly different from a random pruning (p value
      < 0.001). The diagnostic agreement between TIP and neuroanatomists was comparable
      to the agreement between neuroanatomists. The proposed TIP algorithm can be used
      to automatically clean-up noisy fibers in deterministic tractography, with a
      potential to confirm the existence of a fiber connection in basic neuroanatomical
      studies or clinical neurosurgical planning.

PMID- 30218215
TI  - Retraction Note: Purified umbilical cord derived mesenchymal stem cell treatment
      in a case of systemic lupus erythematosus.
AB  - The Editor-in-Chief is retracting this article because the authors have not
      obtained consent to publish from the patient whose details are described in this
      case report. The article has been removed to protect the patient's privacy. Terry
      Grossman has stated that he was not an author on this article. Christopher
      Phillips, Pornpatcharin Wongsaisri and Thein Htut did not reply to correspondence
      about this retraction.

PMID- 30218216
TI  - Left ventricular mechanical dyssynchrony for CAD diagnosis: Does it have
      incremental clinical values?

PMID- 30218217
TI  - Coming-of-age: The ImageGuideTM Registry at three.

PMID- 30218218
TI  - Dose-optimization in nuclear cardiac imaging, time for the next step?

PMID- 30218219
TI  - Human rights approaches to suicide in prison: implications for policy, practice
      and research.
AB  - BACKGROUND: International human right standards place obligations on prison
      authorities to take reasonable steps to prevent suicides in prison and to
      investigate those which occur. Those human rights instruments contain minimum
      standards which states must abide by. Human rights principles can also be used in
      analysis of why suicides occur in prison. METHODS: This paper examines human
      rights standards on suicide and its prevention provided by the United Nations
      Standard Minimum Rules for the Treatment of Prisoners, the European Prison Rules,
      the work of the European Committee for the Prevention of Torture and Inhuman and
      Degrading Treatment or Punishment, and judgments of the European Court of Human
      Rights. Particular consideration is given to European human rights standards in
      light of the literature suggesting that European approaches tend to favour the
      promotion of human rights. A legal research methodology is employed. RESULTS: The
      paper examines key elements of human rights obligations in this field: the duty
      to pay particular attention to prisoners with particular mental health needs;
      duties to provide healthcare of an adequate standard; a duty on the prison
      authorities to ensure a proper information flow within prisons to identify risks;
      and particular duties to avoid using solitary confinement and to deploy
      safeguards when it is used. The paper also describes the obligations to
      investigate which arise after a suicide in prison: there must be an investigation
      instigated by the state which is independent, acts promptly and is open to public
      scrutiny, which is capable of giving rise to a finding of responsibility and is
      able to acquire relevant evidence, and which gives the next of kin of the
      deceased person an opportunity to participate. CONCLUSIONS: All those responsible
      for preventing and responding to suicides in prison must fulfil these human
      rights obligations, and doing so would support a culture of protecting human
      rights in prison. In addition, compliance with the human rights standards
      described here should become a factor more regularly examined in analyses of why
      suicides occur in prison.

PMID- 30218220
TI  - Novel single-stranded, circular DNA virus identified in cats in Japan.
AB  - We detected a novel feline stool-associated circular DNA virus (FeSCV) in fecal
      samples from cats with diarrhea using consensus primers matching those of
      circovirus and cyclovirus. FeSCV is a circular DNA virus containing a genome with
      a total length of 2,046 nt encoding 2 open reading frames. Phylogenetic analyses
      indicated that FeSCV is classified into a clade different from that of circovirus
      and cyclovirus. Since the FeSCVs detected in several cats in the same household
      had genetically similar genomes, these viruses are most likely derived from the
      same origin.

PMID- 30218221
TI  - Impact of migraine on the clinical presentation of insomnia: a population-based
      study.
AB  - BACKGROUND: Insomnia and migraine are closely related; insomnia aggravates
      migraine symptoms. This study was conducted to investigate the impact of migraine
      on the clinical presentation of insomnia symptoms. METHODS: The data of the
      Korean Headache-Sleep Study (KHSS) were used in the present study. The KHSS is a
      nation-wide cross-sectional population-based survey regarding headache and sleep
      in Korean adults aged 19 to 69 years. If a participant's Insomnia Severity Index
      (ISI) score >= 10, she/he was classified as having insomnia. The clinical
      presentation of insomnia symptoms was assessed using total and subcomponent
      scores of the ISI. RESULTS: Of 2695 participants, 290 (10.8%) and 143 (5.3%)
      individuals were assigned as having insomnia and migraine, respectively. The
      proportions of migraine (12.8% vs. 4.4%, p <  0.001) and non-migraine headache
      (59.0% vs. 39.9%, p <  0.001) were higher among individuals with insomnia
      compared to those without insomnia. Among participants with insomnia, total ISI
      scores were not significantly different among participants with migraine, non
      migraine, and non-headache [median and interquartile range: 13.0 (11.0-17.5) vs.
      13.0 (11.0-17.5) vs. 12.0 (11.0-16.0), p = 0.245]. ISI scores for noticeability
      of sleep problems to others were significantly higher among participants with
      migraine [3.0 (2.0-4.0) vs. 2.0 (2.0-3.0), p = 0.011] and non-migraine headache
      [3.0 (2.0-4.0) vs. 2.0 (2.0-3.0), p = 0.001] compared to those without headache
      history. Other ISI subcomponent scores did not significantly differ between
      headache status groups. CONCLUSIONS: Participants with insomnia had an increased
      risk of migraine and non-migraine headache compared to those without insomnia.
      Among participants with insomnia, overall insomnia severity was not significantly
      influenced by the headache status.

PMID- 30218222
TI  - sEMG Based Gait Phase Recognition for Children with Spastic Cerebral Palsy.
AB  - The goal of this study was to examine the optimal strategies for the recognition
      of gait phase based on surface electromyogram (sEMG) of leg muscles while
      children with cerebral palsy (CP) walked on a treadmill. Ten children with CP
      were recruited to participate in this study. sEMG from eight leg muscles and leg
      position signals were recorded while subjects walked on a treadmill. The position
      signals of left and right legs were used to develop a five gait sub-phases
      classifier, i.e., mid stance, terminal stance, pre-swing, mid swing, and terminal
      swing. Seven feature sets of sEMG signals were tested in recognizing the five
      gait sub-phases of children with CP. Results from this study indicated that the
      recognition performance of mean absolute value and zero crossing was better than
      that with other feature sets when using support vector machine (average
      classification accuracy was 89.40%). Further, we found that the performance of
      gait phase recognition is relatively better in pre-swing than other sub-phases,
      and the performance of gait phase recognition is relatively poorer in mid-swing
      than other sub-phases. Results from this study may be used to develop an
      intention-driven robotic gait training system/paradigm for assisting walking in
      children with CP through robotic training.

PMID- 30218223
TI  - A Novel Microfluidic Platform for Biomechano-Stimulations on a Chip.
AB  - Mechanical stress has been proven to be an important factor interfering with many
      biological functions through mechano-sensitive elements within the cells. Despite
      the current interest in mechano-transduction, the development of suitable
      experimental tools is still characterized by the strife to design a compact
      device that allows high-magnification real-time imaging of the stretched cells,
      thus enabling to follow the dynamics of cellular response to mechanical
      stimulations. Here we present a microfluidic multi-layered chip that allows
      mechanical deformation of adherent cells maintaining a fixed focal plane, while
      allowing independent control of the soluble microenvironment. The device was
      optimized with the aid of FEM simulation and fully characterized in terms of
      mechanical deformation. Different cell lines were exposed to tunable mechanical
      strain, which results in continuous area deformation up to 20%. Thanks to the
      coupling of chemical glass etching, 2-dimensional deformation of a thin
      elastomeric membrane and microfluidic cell culture, the developed device allows a
      unique combination of cell mechanical stimulation, in line imaging and accurate
      control of cell culture microenvironment.

PMID- 30218224
TI  - In Vitro Models for Studying Transport Across Epithelial Tissue Barriers.
AB  - Epithelial barriers are the body's natural defense system to regulating passage
      from one domain to another. In our efforts to understand what can and cannot
      cross these barriers, models have emerged as a reductionist approach to
      rigorously study and investigate this question. In particular, in vitro tissue
      models have become prominent as there is an increased exploration of
      understanding biological molecular transport. Herein, we introduce the pertinent
      physiology, then discuss recent studies and approaches for building models of
      five epithelial tissues: skin, the gastrointestinal tract, the lungs, the blood
      brain barrier, and the placenta. In particular, we evaluated literature from the
      past 5 years utilizing a tissue model to evaluate molecular transport. We then
      compare physiology of these tissues and discuss similarities in approaches,
      across tissues, to validate these models. We conclude with a summary of the
      approaches of growing interest across multiple tissues and an outlook on future
      steps to improve these models.

PMID- 30218225
TI  - Stability of point process spiking neuron models.
AB  - Point process regression models, based on generalized linear model (GLM)
      technology, have been widely used for spike train analysis, but a recent paper by
      Gerhard et al. described a kind of instability, in which fitted models can
      generate simulated spike trains with explosive firing rates. We analyze the
      problem by extending the methods of Gerhard et al. First, we improve their
      instability diagnostic and extend it to a wider class of models. Next, we point
      out some common situations in which instability can be traced to model lack of
      fit. Finally, we investigate distinctions between models that use a single filter
      to represent the effects of all spikes prior to any particular time t, as in a
      2008 paper by Pillow et al., and those that allow different filters for each
      spike prior to time t, as in a 2001 paper by Kass and Ventura. We re-analyze the
      data sets used by Gerhard et al., introduce an additional data set that exhibits
      bursting, and use a well-known model described by Izhikevich to simulate spike
      trains from various ground truth scenarios. We conclude that models with multiple
      filters tend to avoid instability, but there are unlikely to be universal rules.
      Instead, care in data fitting is required and models need to be assessed for each
      unique set of data.

PMID- 30218226
TI  - Effects of oral prophylaxis including tongue cleaning on halitosis and gingival
      inflammation in gingivitis patients-a randomized controlled clinical trial.
AB  - OBJECTIVE: The objective of this study was to assess the effect of oral
      prophylaxis including tongue scraping on level of halitosis, clinical periodontal
      parameters and local cytokine response in gingivitis patients. MATERIALS AND
      METHODS: In this randomized controlled clinical trial, 36 gingivitis patients
      were randomly assigned into two subgroups after scaling and polishing. Group 1
      received oral hygiene instructions including the use of tongue scraper; group 2
      received oral hygiene instructions alone without tongue cleaning. Levels of
      volatile sulfur compounds (VSC), organoleptic and tongue coating scores, clinical
      periodontal parameters and gingival crevicular fluid (GCF) samples were collected
      at baseline and 7 days after oral prophylaxis. GCF samples were analyzed using
      multiplexing analysis for the simultaneous measurements of cytokines. The Chi
      square, Mann-Whitney U, Wilcoxon, and Student's paired and unpaired t tests were
      used for statistical analysis. RESULTS: Statistically significant reductions were
      found in terms of clinical periodontal parameters in both groups. However,
      significant improvements in VSC levels, organoleptic and tongue coating scores
      were observed just in tongue scraping group. Moreover, the GCF levels of IL-1beta
      and IL-8 significantly decreased after the treatment in group 1 according to the
      baseline values. CONCLUSION: The present study indicated that oral prophylaxis
      including tongue scraping was effective in improving intra-oral halitosis and pro
      inflammatory cytokine response in GCF in gingivitis patients. CLINICAL RELEVANCE:
      The results suggest that tongue scraping can be taken into consideration in order
      to manage gingival inflammation as well as VSC levels in gingivitis patients but
      further clinical studies are required to judge the clinical relevance.

PMID- 30218227
TI  - Free gingival graft adjunct with low-level laser therapy: a randomized placebo
      controlled parallel group study.
AB  - OBJECTIVES: This study aimed to evaluate the effect of low-level laser therapy
      (LLLT) in terms of enhancing wound healing, reducing free gingival graft (FGG)
      shrinkage and postoperative pain. MATERIALS AND METHODS: Thirty patients were
      randomly assigned to receive either FGG + LLLT (test, n = 15) or FGG + plasebo
      LLLT (control, n = 15). In the test group, a diode laser (810 nm, 0.1 W, energy
      density 6 J/cm2) was applied immediately after surgery and 1, 3, 7, and 14 days
      later. Measurements of the graft surface areas of the groups were made with an
      image-analyzing software at baseline and first, third, and sixth months. Complete
      wound epithelialization and visual analogue scale (VAS) for pain score were
      evaluated after surgery. RESULTS: Shrinkage of the graft was statistically higher
      in the control than the test group at third and sixth months (p < 0.05). In terms
      of epithelization of the graft area, the test and control groups did not show any
      significant difference during the 28-day period (p > 0.05). Besides this,
      statistically significant differences were observed for VAS pain score and the
      number of analgesic used (p < 0.05). CONCLUSIONS: The use of an 810-nm diode
      laser provided additional benefits to FGG in terms of less shrinkage of the graft
      dimensions and postoperative pain. CLINICAL RELEVANCE: Low-level laser therapy
      reduced the shrinkage of free gingival graft's surface area after 6 months and
      enhanced postoperative pain relief.

PMID- 30218228
TI  - Clinical, double blind, randomized controlled trial of experimental adhesive
      protocols in caries-affected dentin.
AB  - OBJECTIVE: To evaluate the clinical performance of posterior resin composite
      restorations regarding experimental and regular adhesive protocols in caries
      affected-dentin (CAD). MATERIAL AND METHODS: A total of 92 class I and class II
      cavities with carious lesions were selected and randomly assigned to the
      following groups: (1) bioactive glass-ceramic powder/two-step etch and rinse
      system, (2) control/two-step etch and rinse system, (3) bioactive glass-ceramic
      powder/two-step self-etching system, and (4) control/two-step self-etching
      system. Two operators carried out the adhesive protocols and restored the
      cavities with a nano-hybrid resin composite. Participants were followed up at 1
      week and 6, 12, and 18 months for clinical evaluation performed by two blinded
      examiners and calibrated according to FDI criteria. Data were analyzed using
      Kruskal-Wallis and Dunn tests with a confidence of 95%. RESULTS: The clinical
      performance of resin composite restoration was not affected by the experimental
      use of an adhesive protocol including a bioactive glass-ceramic powder for 18
      months post-procedure. However, there was a significant difference between group
      2 and group 4 (p < 0.05) for marginal adaptation (18 months). Group 2 was
      significantly different from group 3 (p < 0.05) for fracture of
      material/retention (18 months) and marginal adaptation (1 week); group 2 showed a
      better performance. CONCLUSION: Adhesive protocols can alter the clinical
      performance of posterior restorations in terms of marginal adaptation and the
      fracture of material/retention in CAD. CLINICAL SIGNIFICANCE: Adhesive protocols
      may influence the success of resin composite restorations in CAD; this is
      important because failure can lead to caries, re-incidence, and/or clinical re
      work.

PMID- 30218229
TI  - Mineral density changes in bovine carious dentin after treatment with bioactive
      dental cements: a comparative micro-CT study.
AB  - OBJECTIVES: To evaluate the potential of conventional glass ionomer cement (GIC),
      BiodentineTM, MTA, and Portland cement to induce mineral density changes in
      carious dentin compared to zinc oxide eugenol control cement (ZOE). MATERIALS AND
      METHODS: Fifty blocks of bovine root dentin were prepared and a biofilm model
      using ATCC strains of S.mutans, S.sobrinus, and L.casei was used to promote
      artificial dentin lesions. After demineralization, the blocks were randomly
      divided into the five cement groups. Half of the surface of each specimen
      received the tested material and the other half was covered with wax (control).
      Samples were stored in phosphate buffered saline solution for 30 days and after
      that were scanned in a micro-CT with standardized parameters. Dentin mineral
      density changes were calculated using differences in plot profiles of the exposed
      and control carious dentin. Friedman's test, followed by Wilcoxon signed-rank
      test was used with 5% significance. RESULTS: Mean DeltaZ values for the cements
      were 48.63 +/- 19.09 for the control (ZOE), 63.31 +/- 32.59 for BiodentineTM,
      114.63 +/- 72.92 for GIC, 109.56 +/- 66.28 for MTA, and 106.88 +/- 66.02 for
      Portland cement. All cements showed a statistically significant increase in
      DeltaZ values compared to the control, but BiodentineTM values were statistically
      significantly lower compared to GIC and the other calcium silicate cements.
      CONCLUSIONS: Tested materials present potential to induce mineral density changes
      in carious bovine dentin. MTA, Portland, and GIC showed higher bioactivity
      potential than BiodentineTM. CLINICAL RELEVANCE: Based on minimally invasive
      concept, materials with remineralization potential can be used to preserve
      diseased but still repairable dental tissue.

PMID- 30218230
TI  - Coexistence of oral lichen planus and pemphigus vulgaris.

PMID- 30218231
TI  - Letter to the Editor about the article published in Clinical Oral Investigations
      tilted "Impacted and transmigrated mandibular canines: an analysis of 3D
      radiographic imaging data" (Bertl MH, Frey C, Bertl K, Giannis K, Gahleitner A,
      Strbac GD (2018), Clin Oral Investig, doi: 10.1007/s00784-018-2342-0).

PMID- 30218233
TI  - Self-Focused Attention and Depressive Symptoms in Adults with Autistic Spectrum
      Disorder (ASD).
AB  - Adults with autistic spectrum disorder (ASD) are at high risk of developing
      comorbid depressive symptoms and in the general population self-focused attention
      has been associated with depression. Here, we aimed to examine the relationships
      between aspects of self-focused attention and symptoms of depression in
      individuals with a diagnosis of ASD. 113 adults with a diagnosis of ASD completed
      self-report questionnaires. Results found that higher levels of brooding, and to
      a lesser degree, reflection predicted increased depressive symptoms. However,
      higher levels of private self-consciousness actually predicted decreased
      depressive symptoms. Differential relationships were observed for males and
      females. The current study highlights the importance of using a multidimensional
      approach to examining self-focused attention in ASD, and its important
      relationship with depression.

PMID- 30218232
TI  - Plant species diversity, community structure and invasion status in insular
      primary forests on the Sekimon uplifted limestone (Ogasawara Islands).
AB  - Native forests on oceanic islands are among the most threatened ecosystems. The
      forests formed on Sekimon uplifted limestone in Haha-jima Island (Ogasawara
      Islands) have not yet been destroyed by human activities and remain as primary
      forests harboring several narrow endemic endangered plants. In this paper, we
      described the plant species diversity, community structure, and status of
      invasion by alien plants in the mesic forests of Sekimon. The Sekimon forest was
      characterized by low tree diversity (37 species), high stem density (1731 ha-1),
      and high basal area (63.9 m2 ha-1), comparing with natural forests in world
      islands. The forests were dominated in the number of stems by the sub-tree
      Ardisia sieboldii followed by the trees Pisonia umbellifera and Elaeocarpus
      photiniifolius. The invasive tree Bischofia javanica ranked fourth for basal area
      and third for the number of stems (DBH >= 10 cm), and its distribution expanded,
      especially near a past plantation site. Surveys of forest floor vegetation
      revealed that species richness of vascular plants was 109 species and that many
      alien plants had already invaded the forests. Despite the low species richness of
      alien (16% for vascular flora and 8% for trees), the high frequency of aliens on
      the forest floor suggests that they have colonized successfully in the Sekimon
      forest. Extrapolation analysis based on the rarefaction curves predicted that the
      vascular plants in the Sekimon (25 ha) accounted for 135 species (29.9% of the
      vascular flora of the Ogasawara Islands) and endemic plants were 85 species
      (62.0%). The fact that the 39 vascular species recorded in our plots were listed
      in Japanese Red List suggests that the Sekimon forest should be conserved as a
      sanctuary of biodiversity. Because alien plants are invading the forests without
      apparent anthropogenic disturbance, immediate action to eradicate these invaders
      is highly needed.

PMID- 30218234
TI  - Enhanced microbial lipid production by Cryptococcus albidus in the high-cell
      density continuous cultivation with membrane cell recycling and two-stage
      nutrient limitation.
AB  - As a potential feedstock for biofuel production, a high-cell-density continuous
      culture for the lipid production by Cryptococcus albidus was investigated in this
      study. The influences of dilution rates in the single-stage continuous cultures
      were explored first. To reach a high-cell-density culture, a single-stage
      continuous culture coupled with a membrane cell recycling system was carried out
      at a constant dilution rate of 0.36/h with varied bleeding ratios. The maximum
      lipid productivity of 0.69 g/L/h was achieved with the highest bleeding ratio of
      0.4. To reach a better lipid yield and content, a two-stage continuous
      cultivation was performed by adjusting the C/N ratio in two different stages.
      Finally, a lipid yield of 0.32 g/g and lipid content of 56.4% were obtained. This
      two-stage continuous cultivation, which provided a higher lipid production
      performance, shows a great potential for an industrial-scale biotechnological
      production of microbial lipids and biofuel production.

PMID- 30218235
TI  - Association between number of pairs of opposing posterior teeth, metabolic
      syndrome, and obesity.
AB  - We investigated the relationship between the number of pairs of posterior teeth
      and metabolic syndrome (MetS), abdominal obesity (AO), and obesity, among
      Japanese adults. In 2005, 2,807 Japanese adults aged 25-74 years participated in
      the Survey of Dental Diseases and the National Health and Nutrition Survey. Based
      on the survey data, BMI, AO (JAS) determined by the Japan Atherosclerosis
      Society, AO (IDF) by the International Diabetes Federation, and MetS were
      assessed. Total functional tooth units (t-FTUs) were scored with pairs of
      opposing posterior teeth, including artificial teeth. Subjects were divided into
      three categories of chewing ability based on the score of t-FTUs: Poor (if score
      <= 9), Good (if score = 10-11), and Complete (if score = 12). The relationships
      between chewing ability and BMI >= 25, BMI >= 30, AO (JAS), AO (IDF), and MetS
      were tested using univariate and multivariate logistic regression analysis. The
      chewing ability was significantly associated with MetS, AO, and obesity in the
      univariate and multivariate logistic regression analysis. Adjusted OR of "Poor"
      compared to "Complete" were 1.51 (95% confidence interval (CI), 1.24-1.84) for
      BMI >= 25, 2.10 (95% CI 1.40-3.14) for BMI >= 30, 1.31 (95% CI 1.07-1.61) for AO
      (JAS), 1.40 (95% CI 1.15-1.70) for AO (IDF), and 1.34 (95% CI 1.04-1.72) for
      MetS. All were statistically significant. Preventing tooth loss and maintaining
      pairs of good chewing ability may be important factors in preventing MetS, AO,
      and obesity.

PMID- 30218236
TI  - Ineffective appropriate shocks in coronary artery spasm disease: when
      defibrillation is not enough.

PMID- 30218237
TI  - Conscious sedation during subcutaneous implantable cardioverter-defibrillator
      implantation using the intermuscular technique.
AB  - BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD)
      system is an established therapy for the prevention of sudden cardiac death (SCD)
      and an alternative to a transvenous implantable cardioverter-defibrillator (ICD)
      system in selected patients. S-ICDs are usually implanted under general
      anesthesia. The purpose of the present study was to describe the technical
      feasibility and safety of local anesthesia with conscious sedation as an
      alternative to general anesthesia during S-ICD implantation using the
      intermuscular technique. METHODS: We conducted a retrospective, single-center
      study on patients undergoing S-ICD implantation using the intermuscular technique
      at our center between February 2016 and May 2018. All procedures were performed
      under controlled sedation with propofol and midazolam. Local anesthesia was used
      for all procedures. RESULTS: Twenty-two patients (17 men and 5 women) with a mean
      age of 51.1 +/- 16.2 years were included. The indication for S-ICD implantation
      was primary prevention in 18 (81.8%) patients. The mean dose of midazolam and
      propofol administered was 7.8 +/- 2.3 mg and 72.7 +/- 37.4 mg, respectively. The
      procedural success rate was 100%, with no apneic or hypoxic episodes or other
      complications requiring therapeutic intervention. None of the patients required
      conversion to general anesthesia. All patients were comfortable with the position
      and appearance of the device. CONCLUSIONS: Our findings suggest that local
      anesthesia with conscious sedation using propofol and midazolam is a safe and
      feasible option for S-ICD implantation procedures using an intermuscular
      technique.

PMID- 30218238
TI  - Nimbolide ameliorates fibrosis and inflammation in experimental murine model of
      bleomycin-induced scleroderma.
AB  - BACKGROUND: Clinical manifestations of skin fibrosis are very variable and
      ambiguous, making its management quite critical and challenging. The lack of
      appropriate established pharmacological interventions make its treatment even
      more complicated. Intricate details of the underlying pathogenesis are thus
      imperative to further explore different treatment possibilities. Of note, the TGF
      beta/Smad signaling axis and epithelial to mesenchymal transition (EMT) are the
      principal offenders in this fibrotic disorder. OBJECTIVE: Our current study is
      aimed at demonstrating the antifibrotic and anti-inflammatory potential of
      nimbolide, a triterpene derived from Indian traditional plant neem, in a murine
      model of Bleomycin-induced scleroderma. METHODS: Male C57BL/6 mice were
      administered with Bleomycin injections subcutaneously, daily for 28 days, at a
      constant site on the dorsum of the mice. Treatment with nimbolide lasted from day
      1 to day 28. At the time of study termination, the injected sites were collected
      and stored suitably to conduct further molecular experiments and protein
      expression studies. RESULTS AND CONCLUSION: The results of our study show that
      nimbolide can significantly intervene in the TGF-beta/Smad signaling axis and the
      consequent EMT process, thus attenuating deposition of extracellular matrix.
      Nimbolide also profoundly caused the regression of established inflammation
      driven fibrosis, thus demonstrating both antifibrotic and anti-inflammatory
      activities. Another commendable finding of this study is that nimbolide was able
      to decrease the levels of LOXL2, a collagen cross-linker, which is aberrantly
      expressed in scleroderma. Although further mechanistic studies are required, our
      study displays nimbolide for the first time as a potent antifibrotic agent which
      can be used as a pharmacological intervention for the treatment of scleroderma.

PMID- 30218239
TI  - Diagnostic accuracy of MRI with extracellular vs. hepatobiliary contrast material
      for detection of residual hepatocellular carcinoma after locoregional treatment.
AB  - PURPOSE: To compare the diagnostic accuracy of extracellular gadolinium-based
      contrast-enhanced MRI (Gd-MRI) and gadoxetic acid-enhanced MRI (EOB-MRI) for the
      assessment of hepatocellular carcinoma (HCC) response to locoregional therapy
      (LRT) using explant correlation as the reference standard. METHODS: Forty-nine
      subjects with cirrhosis and HCC treated with LRT who underwent liver MRI using
      either Gd-MRI (n = 26) or EOB-MRI (n = 23) within 90 days of liver
      transplantation were included. Four radiologists reviewed the MR images blinded
      to histology to determine the size and percentage of viable residual HCC using a
      per-lesion explant reference standard. Sensitivities, specificities, accuracies,
      and agreement with histology for the detection residual HCC were calculated.
      RESULTS: Gd-MRI had greater agreement with histology (ICC: 0.98 [0.95-0.99] vs.
      0.80 [0.63-0.90]) and greater sensitivity for viable HCC (76% [13/17 50-93%] vs.
      58% [7/12; 28-85%]) than EOB-MRI; specificities were similar (84% [16/19; 60-97%]
      vs. 85% [23/27; 66-96%]). Areas under ROC curves for detecting residual viable
      tumor were 0.80 (0.64-0.92) for Gd-MRI and 0.72 (0.55-0.85) for EOB-MRI. Gd-MRI
      had greater inter-rater agreement than EOB-MRI for determining the size of
      residual viable HCC (ICC: 0.96 [0.92-0.98] vs. 0.85 [0.72-0.92]). CONCLUSION: Gd
      MRI may be more accurate and precise than EOB-MRI for the assessment of viable
      HCC following LRT.

PMID- 30218240
TI  - The possible protective role of zinc oxide nanoparticles (ZnONPs) on testicular
      and epididymal structure and sperm parameters in nicotine-treated adult rats (a
      histological and biochemical study).
AB  - Exposure to nicotine in smoking contributes to most unexplained male infertility
      but the mechanisms remain to be fully elucidated. Zinc (Zn) is an essential trace
      element in normal growth, development and reproduction. Zinc oxide nanoparticles
      (ZnONPs) are well-known antioxidants. Therefore, this work was designed to
      investigate the potential ability of ZnONPs to protect testis and epididymis in
      nicotine-treated rats. Forty adult male Wistar albino rats were divided into
      control group and two experimental groups (treated and supplemented rats). In the
      treated group, rats received nicotine at a dose of 1 mg/kg/day orally for 30
      days. Rats in the supplemented group received ZnONPs (10 mg/kg/day) with nicotine
      (1 mg/kg/day), orally for the same period. Testicular and epididymal sections
      were stained with H&E to assess the histological changes. Negrosin-eosin staining
      of epididymal sperms was performed to assess their viability and morphological
      changes. Serum testosterone, FSH and LH levels were assessed. Also, oxidative
      stress parameters and semiquantitative real-time PCR for steroidogenic enzymes
      were measured. Morphometric studies of both organs were statistically analyzed.
      Mild to severe testicular and epididymal structural changes together with sperm
      morphological abnormalities were detected in nicotine-treated rats. Biochemical
      results also showed a decrease in all measured parameters except for an increased
      malondialdehyde (MDA) level that meant deterioration of their reproductive
      function. On the other hand, ZnONP supplementation in the last group showed an
      obvious improvement in all investigated parameters.

PMID- 30218241
TI  - Mucin 2 (MUC2) promoter characterization: an overview.
AB  - Transgenic livestock have been studied with a well-known interest in improving
      quantitative and qualitative traits. In order to direct heterologous gene
      expression, it is indispensable to identify and characterize a promoter suitable
      for directing the expression of the gene of interest (GOI) in a tissue-specific
      way. The gastrointestinal tract is a desirable target for gene expression in
      several mammalian models. Throughout the surface of the intestinal epithelium,
      there is an intricate polymer network, formed by gel-forming mucins (especially
      MUC2 and MUC5AC, of which MUC2 is the major one), which plays a protective role
      due to the formation of a physical, chemical and immunological barrier between
      the organism and the environment. The characterization of the gel-forming mucins
      is difficult because of their large size and repetitive DNA sequences and
      domains. The main mucin in the small and large intestine, mucin 2 (MUC2), is
      expressed specifically in goblet cells. MUC2 plays an important role in
      intestinal homeostasis and its disruption is associated with several diseases and
      carcinomas. This mucin is also an important marker for elucidating mechanisms
      that regulate differentiation of the secretory cell lineage. This review presents
      the state of the art of MUC2 promoter structure and functional characterization.

PMID- 30218242
TI  - Pregnancy-associated Cushing's disease? An exploratory retrospective study.
AB  - PURPOSE: In most clinical series of Cushing's disease (CD), over 80% of patients
      are women, many of whom are of reproductive age. The year following pregnancy may
      be a common time to develop CD. We sought to establish the incidence of CD onset
      associated with pregnancy. METHODS: A retrospective review was conducted for
      patients with biochemically-proven CD. Demographics, clinical history,
      biochemistry, imaging, pathology, and outcomes were reviewed. Pregnancy
      associated CD was defined as symptom onset within 1 year of childbirth. RESULTS:
      Over 10 years, 77 patients including 64 women (84%), with CD underwent endonasal
      surgery. Of the 64 women, 64% were of reproductive age (15-45 years) at the time
      of diagnosis, and 11 (27%) met criteria for pregnancy-associated CD. Of these 11
      women, median number of pregnancies prior to onset of CD was 2 (range 1-4)
      compared to zero (range 0-7) for 30 other women with CD onset during reproductive
      age (p = 0.0024). With an average follow-up of 47 +/- 34 months, sustained
      surgical remission rates for woman with pregnancy-associated CD, other women of
      reproductive age, and women not of reproductive age were 91%, 80% and 83%,
      respectively. The average lag-time from symptom onset to diagnosis for women with
      pregnancy-associated CD was 4 +/- 2 years. CONCLUSIONS: In this exploratory
      study, over one quarter of women of reproductive age with CD appeared to have
      symptomatic disease onset within 1 year of childbirth. This relatively high rate
      of pregnancy-associated CD suggests a possible causal relationship related to the
      stress of pregnancy and pituitary corticotroph hyperactivity in the peripartum
      period. This possible association suggests a heightened degree of clinical
      suspicion and biochemical testing for CD may be warranted after childbirth.
      Further study of this possible link between pregnancy and CD is warranted.

PMID- 30218243
TI  - Comparison of Outcomes for Elderly Gastric Cancer Patients at Least 80 Years of
      Age Following Gastrectomy in the United States and China.
AB  - OBJECTIVE: The aim of this study was to compare gastric cancer (GC) patients aged
      80 years or older undergoing gastrectomy at two high-volume cancer centers in the
      US and China. METHODS: Patients aged >= 80 years who underwent R0 resection at
      Memorial Sloan Kettering Cancer Center (MSKCC) in New York, USA (n = 159), and
      Fujian Medical University Union Hospital (FMUUH) in Fujian, China (n = 118) from
      January 2000 to December 2013 were included. Demographic, surgical, and
      pathologic variables were compared, and factors associated with survival were
      determined via multivariate analysis. RESULTS: The number of patients increased
      annually in the FMUUH cohort but not in the MSKCC cohort. Patients at MSKCC were
      slightly older (mean age 83.7 vs. 82.7 years), more commonly female (38 vs. 19%),
      and had higher average body mass index (BMI; 26 vs. 23). Treatment at FMUUH more
      frequently employed total gastrectomy (59 vs. 20%) and laparoscopic surgery (65
      vs. 7%), and less frequently included adjuvant therapy (11 vs. 18%). In addition,
      FMUUH patients had larger tumors of more advanced T, N, and TNM stage. Morbidity
      (35 vs. 25%, p = 0.08) and 30-day mortality (2.5 vs. 3.3%, p = 0.67) were similar
      between the cohorts. For each TNM stage, there was no significant difference
      between MSKCC and FMUUH patients in 5-year overall survival and disease-specific
      survival (DSS). TNM stage was the only independent predictor of DSS for both
      cohorts. CONCLUSIONS: Patients >= 80 years of age selected for gastrectomy for GC
      at MSKCC and FMUUH had acceptable morbidity and mortality, and DSS was primarily
      dependent on TNM stage.

PMID- 30218244
TI  - Drivers of Cost for Pancreatic Surgery: It's Not About Hospital Volume.
AB  - BACKGROUND: Outcomes for pancreatic resection have been studied extensively due
      to the high morbidity and mortality rates, with high-volume centers achieving
      superior outcomes. Ongoing investigations include healthcare costs, given the
      national focus on reducing expenditures. Therefore, we sought to evaluate the
      relationships between pancreatic surgery costs with perioperative outcomes and
      volume status. METHODS: We performed a retrospective analysis of 27,653 patients
      who underwent elective pancreatic resections from October 2013 to June 2017 using
      the Vizient database. Costs were calculated from charges using cost-charge ratios
      and adjusted for geographic variation. Generalized linear modeling adjusting for
      demographic, clinical, and operation characteristics was performed to assess the
      relationships between cost and length of stay, complications, in-hospital
      mortality, readmissions, and hospital volume. High-volume centers were defined as
      hospitals performing >= 19 operations annually. RESULTS: The unadjusted mean cost
      for pancreatic resection and corresponding hospitalization was $20,352. There
      were no differences in mean costs for pancreatectomies performed at high- and low
      volume centers [- $1175, 95% confidence interval (CI) - $3254 to $904, p = 0.27].
      In subgroup analysis comparing adjusted mean costs at high- and low-volume
      centers, there was no difference among patients without an adverse outcome (-
      $99, 95% CI - $1612 to 1414, p = 0.90), one or more adverse outcomes (- $1586,
      95% CI - $4771 to 1599, p = 0.33), or one or more complications (- $2835, 95% CI 
      $7588 to 1919, p = 0.24). CONCLUSIONS: While high-volume hospitals have fewer
      adverse outcomes, there is no relationship between surgical volume and costs,
      which suggests that, in itself, surgical volume is not an indicator of improved
      healthcare efficiency reflected by lower costs. Patient referral to high-volume
      centers may not reduce overall healthcare expenditures for pancreatic operations.

PMID- 30218245
TI  - The Intraoperative Portable Gamma Camera Is an Important Adjunct to the Gamma
      Probe in Identifying Melanoma Sentinel Lymph Nodes.

PMID- 30218246
TI  - Adjuvant and Neoadjuvant Therapy, Treatment for Advanced Disease, and Genetic
      Considerations for Adrenocortical Carcinoma: An Update from the SSO Endocrine and
      Head and Neck Disease Site Working Group.
AB  - This is the second of a two-part review on adrenocortical carcinoma (ACC)
      management. While margin-negative resection provides the only potential cure for
      ACC, recurrence rates remain high. Furthermore, many patients present with
      locally advanced, unresectable tumors and/or diffuse metastases. As a result,
      selecting patients for adjuvant therapy and understanding systemic therapy
      options for advanced ACC is important. Herein, we detail the current literature
      supporting the use of adjuvant mitotane therapy, consideration of adjuvant
      radiation therapy, and utility of cytotoxic chemotherapy in patients with
      advanced disease. Ongoing investigation into molecular targeted agents,
      immunotherapy, and inhibitors of steroidogenesis for the treatment of ACC are
      also highlighted. Lastly, the importance of genetic counseling in patients with
      ACC is addressed as up to 10% of patients will have an identifiable hereditary
      syndrome.

PMID- 30218247
TI  - Hepatic Resection for Non-functional Neuroendocrine Liver Metastasis: Does the
      Presence of Unresected Primary Tumor or Extrahepatic Metastatic Disease Matter?
AB  - OBJECTIVES: The objective of this study was to assess the impact of unresected
      primary tumor, as well as extrahepatic metastasis, on the long-term prognosis of
      patients undergoing hepatic resection for non-functional neuroendocrine liver
      metastasis (NF-NELM). METHODS: Patients who underwent hepatic resection for NF
      NELM were identified from a multi-institutional database. Data on clinical and
      pathological details, as well as the long-term overall survival (OS) were
      obtained and compared. Propensity score matching was performed to generate
      matched pairs of patients. RESULTS: Among the 332 patients with NF-NELM, 281
      (84.6%) underwent primary tumor resection, while 51 (15.4%) did not. Patients who
      underwent primary resection were more likely to have a pancreatic primary and
      metachronous NELM. The long-term OS of patients who did and did not have the
      primary neuroendocrine tumor (NET) resected was comparable on both unmatched (10
      year survival rate 66.8% vs. 54.0%, p = 0.192) and matched (10-year survival rate
      75.7% vs. 60.4%, p = 0.271) analyses. In contrast, patients with NF-NELM and
      extrahepatic metastasis had a worse OS following resection compared with patients
      who had intrahepatic-only metastasis on unmatched (10-year survival rate 37.5%
      vs. 69.3%, p = 0.002) and matched (10-year survival rate 37.5% vs. 86.3%, p =
      0.011) analyses. On multivariable analysis, while resection of the primary NET
      was not associated with OS (hazard ratio [HR] 0.7, 95% confidence interval [CI]
      0.4-1.2, p = 0.195), the presence of extrahepatic metastasis was independently
      associated with long-term risk of death (HR 3.9, 95% CI 1.7-9.2, p = 0.002).
      CONCLUSIONS: While surgery should be considered for patients with NF-NELM who
      have an unresectable primary tumor, operative resection of NF-NELM may not be as
      beneficial in patients with extrahepatic disease.

PMID- 30218248
TI  - Robotic Versus Laparoscopic Right Colectomy with Complete Mesocolic Excision for
      the Treatment of Colon Cancer: Perioperative Outcomes and 5-Year Survival in a
      Consecutive Series of 202 Patients.
AB  - BACKGROUND: During the past decade, the concept of complete mesocolic excision
      (CME) has emerged as a possible strategy to minimize recurrence for right colon
      cancers. The purpose of this study was to compare robotic versus laparoscopic CME
      in performing right colectomy for cancer. METHODS: Pertinent data of all patients
      who underwent robotic or laparoscopic right colectomy with CME using a
      Pfannenstiel incision and intracorporeal anastomosis performed between October
      2005 and November 2015 were entered in a prospectively maintained database.
      RESULTS: A total of 202 patients underwent robotic (n = 101) or laparoscopic (n =
      101) right colectomy within the study period. Patient characteristics were
      equivalent between groups. The robotic group showed a statistically significant
      reduction in conversion rate (0% vs. 6.9%, p = 0.01) but a longer operative time
      (279 min vs. 236 min, p < 0.001) compared with the laparoscopic group. There were
      no other differences in perioperative clinical or pathological outcomes. Five
      years overall survival was 77 versus 73 months for the robotic versus
      laparoscopic groups (p = 0.64). The disease-free survival (DFS) rates were 85%
      and 83% for the robotic versus laparoscopic groups (p = 0.58). Among UICC stage
      III patients, there was a slight but not significant difference in 5-year DFS for
      the robotic group (81 vs. 68 months; p = 0.122). CONCLUSIONS: Both approaches for
      right colectomy with CME were safe and feasible and resulted in excellent
      survival. Robotic assistance was beneficial for performing intracorporeal
      anastomosis and dissection as evidenced by the lower conversion rates. Further
      robotic experience may shorten the operative time.

PMID- 30218249
TI  - A Novel Navigation for Laparoscopic Anatomic Liver Resection Using Indocyanine
      Green Fluorescence.
AB  - BACKGROUND: Among all laparoscopic liver resection techniques, anatomic liver
      resection is one of the most challenging procedures, with disorientation readily
      occurring during the laparoscopic approach compared with the open approach.1
      Thus, navigation is warranted for laparoscopic anatomic liver resection. Recent
      research has remarkably established intraoperative fluorescence imaging
      techniques using indocyanine green fluorescence (ICG) in the field of liver
      surgery.2-4 This report describes real-time navigation for anatomic liver
      resection using the novel ICG system, PINPOINT (Stryker, Kalamazoo, MI). METHODS:
      The target Glissonian pedicle was identified and temporally clamped after
      confirmation of blood supply to the preserved adjacent segment using
      ultrasonography. Next, 1.5 mg of ICG was intravenously administered using the
      negative counterstaining method. After 3 min of administration, the ICG-stained
      area could be readily recognized. Parenchymal transection was subsequently
      initiated along the interface between the ICG-positive and ICG-negative areas
      using the Pringle maneuver. RESULTS: Using PINPOINT, laparoscopic anatomic liver
      resection was performed for 16 patients. The extent of liver resection comprised
      two left hepatectomies, three right-anterior sectionectomies, three right
      anterior sectionectomies, and eight segmentectomies. The identification rate of
      clear demarcations in the ICG images was 100%. The intraoperative blood loss was
      226 mL, and the operative time was 305 min. Only one patient encountered the
      major postoperative complication of ascites, and all the patients attained R0
      resection. CONCLUSIONS: Because the images provided by the ICG system are clearer
      than conventional ICG images, it could facilitate real-time navigation for
      laparoscopic anatomic liver resection.

PMID- 30218250
TI  - Total Laparoscopic Pancreaticoduodenectomy with Venous Reconstruction for
      Pancreatic Head Cancer with Involvement of the Superior Mesenteric Vein-Portal
      Vein Confluence.
AB  - BACKGROUND: Laparoscopic pancreaticoduodenectomy with venous reconstruction is
      not commonly performed due to its technical challenges. In this video, we focus
      on the technical aspects for how to perform this procedure safely. METHODS: In a
      69-year-old female with jaundice and diarrhea, a computed tomography scan showed
      a mass in the head of the pancreas, with a 180-degree involvement of the superior
      mesenteric vein. Endoscopic retrograde cholangiopancreatography with stenting was
      performed together with endoscopic ultrasound and fine-needle aspiration. Biopsy
      showed well-differentiated adenocarcinoma. The patient underwent six cycles of
      neoadjuvant chemotherapy, with reduction of the vein involvement to 90 degrees.
      The mass invaded the right lateral aspect of the superior mesenteric vein-portal
      vein confluence. As a result, this portion of the vein was removed en bloc with
      the specimen. The vascular defect was repaired using two running sutures. Once
      the choledocojejunostomy and intussuscepted pancreatico-gastric anastomosis were
      completed, the specimen was removed via a small subxiphoid incision. RESULTS:
      Operative time was 6 h and 30 min, blood loss was 50 mL, and hospital stay was 12
      days. Histopathological examination was ypT3 N1 (1 of 18 lymph nodes was
      positive). All margins were negative. CONCLUSION: Laparoscopic
      pancreaticoduodenectomy with vascular reconstruction can be performed safely in
      selected cases of pancreatic head cancer with vein involvement. Advanced
      laparoscopic skills are necessary to complete such procedures safely.

PMID- 30218251
TI  - Optimal surgical intervention for achalasia: laparoscopic or robotic approach.
AB  - Laparoscopic esophageal myotomy is the standard surgical intervention for
      achalasia. Compared to standard laparoscopic techniques, use of the robot has
      theoretical advantages of improved visualization and dexterity. We evaluated the
      University of Arizona's experience with the two alternatives to compare outcomes.
      Patients who underwent either laparoscopic or robot-assisted myotomy were
      identified from a retrospective database from 1/1/2006 to 12/31/2015. Patient
      demographics, prior treatment, intra-operative complications, operative time,
      post-operative length of stay and complications, and long-term results were
      compared between the two groups. We identified 35 laparoscopic and 37 robot
      assisted Heller myotomies performed by multiple surgeons. Patient demographics
      were similar between the two groups with no statistical difference in age,
      gender, previous operations, pre-operative Botox or dilation treatment, or pre-op
      Eckardt score. In univariate analysis, the patients with the robotic procedure
      received a longer myotomy (5.85 cm vs. 5.56 cm for esophageal and 2.92 cm vs.
      2.68 cm for gastric) and had a lower post-operative Eckardt score (0.51 vs.
      1.09). A trend toward lower incidence of recurrent achalasia symptoms was found
      in the robotic group (0 patient vs. 4 patients) compared with those who had
      laparoscopic surgery (p < 0.05). Multivariate analysis showed that a longer
      gastric myotomy was associated with a lower recurrence rate (p = 0.0002). Both
      laparoscopic and robot-assisted Heller myotomy can provide definitive treatment
      of achalasia with good results and few complications. The mechanical advantage
      provided by the robotic approach may improve outcomes by providing a more
      complete myotomy and durable long-term result.

PMID- 30218252
TI  - Three-dimensional computed tomographic angiography with computed tomographic
      colonography for laparoscopic colorectal surgery.
AB  - PURPOSE: To prospectively correlate the preoperative vessel anatomy in three
      dimensional computed tomographic angiography with computed tomographic
      colonography (3D-CTA with CTC) with that in laparoscopic surgery for colorectal
      cancer. METHODS: The study protocol was approved by our institutional review
      board. The study population consisted of 101 patients with colon cancer who
      underwent 3D-CTA with CTC between June 2016 and January 2018. Two radiologists
      assessed the branching patterns of sigmoid arteries (SAs) and right colonic
      artery (RCA), the position between the ileocolic artery (ICA) and superior
      mesenteric vein (SMV), and the existence of an accessory middle colonic artery
      (aMCA). The vessel anatomy on 3D-CTA with CTC was correlated with that of
      intraoperative findings. RESULTS: Ninety-eight examinations (97.0%) were
      technically successful. Between preoperative and intraoperative vessel anatomy,
      the branching patterns of SAs were concordant in all 29 cases with rectosigmoid
      and descending colon cancer. The branching patterns of RCA and the position
      between the ICA and SMV were completely concordant in 32 cases of cecal and
      ascending colon cancer. No aMCA was identified either intraoperatively or by
      imaging analysis. CONCLUSIONS: 3D-CTA with CTC guided the surgeons to determine
      the resection margin of the relevant vessels for laparoscopic colorectal surgery.

PMID- 30218253
TI  - Definitive radiotherapy for hilar and/or mediastinal lymph node metastases after
      stereotactic body radiotherapy or surgery for stage I non-small cell lung cancer:
      5-year results.
AB  - PURPOSE: The optimal treatment for hilar or mediastinal lymph node (LN)
      recurrence developing after stereotactic body radiotherapy (SBRT) for stage I non
      small cell lung cancer remains unclear. This study evaluated 5-year results of
      radiotherapy in such patients in comparison with those for postoperative LN
      metastases. MATERIALS AND METHODS: Between 2004 and 2013, 27 patients with hilar
      and/or mediastinal LN metastases without local recurrence and distant metastasis
      after SBRT (n = 14) or surgery (n = 13) were treated with definitive conventional
      radiotherapy. The median total dose for treating metastatic LN was 60 Gy for the
      post-SBRT group and 66 Gy for the post-surgery group. RESULTS: The median follow
      up for the 5 surviving patients was 62 months. The overall survival, cause
      specific survival, progression-free survival, and local control rates at 5 years
      after mediastinal irradiation were 14%, 45%, 21%, and 58%, respectively, for the
      14 patients in the post-SBRT group. These rates were 36%, 45%, 39%, and 92%,
      respectively for the post-surgery group (p = 0.066, 0.64, 0.38, and 0.41,
      respectively). Four patients in the post-SBRT group survived 3 or more years
      (range 36-92 months) after mediastinal irradiation. CONCLUSIONS: A proportion of
      patients in both groups achieved long-term survival by conventional radiotherapy.

PMID- 30218255
TI  - Human Genetic Variation and HIV/AIDS in Papua New Guinea: Time to Connect the
      Dots.
AB  - PURPOSE OF REVIEW: Human genetic polymorphisms known to influence HIV acquisition
      and disease progression occur in Papua New Guinea (PNG). However, no genetic
      association study has been reported so far. In this article, we review research
      findings, with a view to stimulate genotype-to-phenotype research. RECENT
      FINDINGS: PNG, a country in Oceania, has a high prevalence of HIV and many
      sexually transmitted infections. While limited data is available from this
      country regarding the distribution of human genetic polymorphisms known to
      influence clinical outcomes of HIV/AIDS, genetic association studies are lacking.
      Our studies, in the past decade, have revealed that polymorphisms in chemokine
      receptor-ligand (CCR2-CCR5, CXCL12), innate immune (Toll-like receptor, beta
      defensin), and antiretroviral drug-metabolism enzyme (CYP2B6, UGT2B7) genes are
      prevalent in PNG. Although our results need to be validated in further studies,
      it is urgent to pursue large-scale, comprehensive genetic association studies
      that include these as well as additional genetic polymorphisms.

PMID- 30218254
TI  - The Role of the Glucosinolate-Myrosinase System in Mediating Greater Resistance
      of Barbarea verna than B. vulgaris to Mamestra brassicae Larvae.
AB  - We investigated the influences of two structurally similar glucosinolates,
      phenethylglucosinolate (gluconasturtiin, NAS) and its (S)-2-hydroxyl derivative
      glucobarbarin (BAR), as well as their hydrolysis products on larvae of the
      generalist Mamestra brassicae (Lepidoptera: Noctuidae). Previous results
      suggested a higher defensive activity of BAR than NAS based on resistance toward
      M. brassicae larvae of natural plant genotypes of Barbarea vulgaris R. Br.
      (Brassicaceae) dominated by BAR. In the present study, the hypothesis of a higher
      defensive activity of BAR than NAS was tested by comparing two Barbarea species
      similarly dominated either by BAR or by NAS and by testing effects of isolated
      BAR and NAS on larval survival and feeding preferences. Larvae reared on leaf
      disks of B. verna (Mill.) Asch. had a lower survival than those reared on B.
      vulgaris P- and G-chemotypes. Leaves of B. verna were dominated by NAS, whereas
      B. vulgaris chemotypes were dominated by BAR or its epimer. In addition, B. verna
      leaves showed a threefold higher activity of the glucosinolate-activating
      myrosinase enzymes. The main product of NAS from breakdown by endogenous enzymes
      including myrosinases ("autolysis") in B. verna leaves was phenethyl
      isothiocyanate, while the main products of BAR in autolyzed B. vulgaris leaves
      were a cyclized isothiocyanate product, namely an oxazolidine-2-thione, and a
      downstream metabolite, an oxazolidin-2-one. The glucosinolates BAR and NAS were
      isolated and offered to larvae on disks of cabbage. Both glucosinolates exerted
      similar negative effects on larval survival but effects of NAS tended to be more
      detrimental. Low concentrations of BAR, but not of NAS, stimulated larval
      feeding, whereas high BAR concentrations acted deterrent. NAS only tended to be
      deterrent at the highest concentration, but the difference was not significant.
      Recoveries of NAS and BAR on cabbage leaf disks were similar, and when hydrolyzed
      by mechanical leaf damage, the same isothiocyanate-type products as in Barbarea
      plants were formed with further conversion of BAR to cyclic products, (R)-5
      phenyloxazolidine-2-thione [(R)-barbarin] and (R)-5-phenyloxazolidin-2-one [(R)
      resedine]. We conclude that a previously proposed generally higher defensive
      activity of BAR than NAS to M. brassicae larvae could not be confirmed. Indeed,
      the higher resistance of NAS-containing B. verna plants may be due to a combined
      effect of rather high concentrations of NAS and a relatively high myrosinase
      activity or other plant traits not investigated yet.

PMID- 30218256
TI  - Contamination assessment and health risk of arsenic exposure to stairway dust in
      the zinc smelting district, Northeast China.
AB  - Stairway dust samples were collected from residential communities in Huludao city
      to investigate population health risk of arsenic (As) exposure through stairway
      dust. ArcGIS software was used to analyze As spatial distribution in Huludao
      city. Hazard index was applied to assess health risk due to exposure to As in
      stairway dust. The results were that As concentrations ranged from 13.26 to
      237.58 mg kg-1, and the mean value was 59.64 mg kg-1, which was seven times as
      high as the background value of Liaoning Province. The pattern of spatial
      distribution was concentric rings as the center of Huludao zinc plant, with the
      extension to the northeast and southwest. The average value of Igeo was 2.176,
      which fell into moderately polluted level. For non-carcinogenic risk, the hazard
      indexes were less than 1, indicating that there was almost no health risk for
      residents exposed to stairway dust. But population risk exposure to dust would
      increase rapidly with exposure time in stairway. The highest contribution to the
      overall figure of non-carcinogenic risk and carcinogenic risk appeared to be
      ingestion of substrate particles followed by inhalation pathway and dermal
      absorption of As in dust samples. And for carcinogenic risk, the risk values were
      lower than the threshold range of EPA's safe limits (1 * 10-6 and 1 * 10-4),
      suggesting that potential cancer risk of As due to exposure to stairway dust can
      be acceptable.

PMID- 30218257
TI  - Phenolic Compounds Determined by LC-MS/MS and In Vitro Antioxidant Capacity of
      Brazilian Fruits in Two Edible Ripening Stages.
AB  - The aim of this study was to investigate the free individual phenolics and the in
      vitro antioxidant capacity of blackberry, acerola, yellow guava, guabiju,
      jambolan and jabuticaba fruits in two edible stages. Of the thirty-three
      phenolics investigated by liquid chromatography - tandem mass spectrometry (LC
      MS/MS), twenty-five were quantified and the major ones were catechin,
      isoquercitrin, epicatechin and gallic acid. The highest values for the total
      phenolic content (in dry matter) were observed for acerola (83.6 to 97.7 mg
      gallic acid equivalents g-1 DM) and blackberry (18.9 to 28.3 mg gallic acid
      equivalents g-1 DM); however, acerola, jabuticaba, and blackberry showed the
      highest antioxidant capacities (134.6 to 1120.4 mg Trolox equivalents g-1 for 2,2
      diphenyl-1-picrylhydrazyl and 43.6 to 501.8 MUmol Trolox equivalents g-1 for
      ferric reducing antioxidant power). For most fruits, the antioxidant capacity
      decreased during the ripening, possibly due to a decrease in the concentration of
      most of the phenolics.

PMID- 30218258
TI  - Changes in the photosynthetic apparatus and lipid droplet formation in
      Chlamydomonas reinhardtii under iron deficiency.
AB  - The unicellular photosynthetic alga Chlamydomonas reinhardtii was propagated in
      iron deficiency medium and patterns of growth, photosynthetic efficiency, lipid
      accumulation, as well as the expression of lipid biosynthetic and photosynthesis
      related proteins were analysed and compared with iron-sufficient growth
      conditions. As expected, the photosynthetic rate was reduced (maximally after 4
      days of growth) as a result of increased non-photochemical quenching (NPQ).
      Surprisingly, the stress-response protein LHCSR3 was expressed in conditions of
      iron deficiency that cause NPQ induction. In addition, the protein contents of
      both the PSI and PSII reaction centres were gradually reduced during growth in
      iron deficiency medium. Interestingly, the two generations of Fe deficiency cells
      could be able to recover the photosynthesis but the second generation cells
      recovered much slower as these cells were severely in shock. Analysis by flow
      cytometry with fluorescence-activated cell sorting and thin layer chromatography
      showed that iron deficiency also induced the accumulation of triacylglycerides
      (TAG), which resulted in the formation of lipid droplets. This was most
      significant between 48 and 72 h of growth. Dramatic increases in DGAT2A and PDAT1
      levels were caused by iron starvation, which indicated that the biosynthesis of
      TAG had been increased. Analysis using gas chromatography mass spectrometry
      showed that levels of 16:0, 18:0, 18:2 and 18:3Delta9,12,15 fatty acids were
      significantly elevated. The results of this study highlight the genes/enzymes of
      Chlamydomonas that affect lipid synthesis through their influence on
      photosynthesis, and these represent potential targets of metabolic engineering to
      develop strains for biofuel production.

PMID- 30218259
TI  - Use of Computerized Clinical Decision Support for Diagnostic Stewardship in
      Clostridioides difficile testing: an Academic Hospital Quasi-Experimental Study.

PMID- 30218260
TI  - Implementation of Patient and Family Advisory Councils in Primary Care Practices
      in a Large, Integrated Health System.

PMID- 30218261
TI  - Combination of DXA and BIS body composition measurements is highly correlated
      with physical function-an approach to improve muscle mass assessment.
AB  - RATIONALE: Fluid volume estimates may help predict functional status and thereby
      improve sarcopenia diagnosis. MAIN RESULT: Bioimpedance-derived fluid volume,
      combined with DXA, improves identification of jump power over traditional
      measures. SIGNIFICANCE: DXA-measured lean mass should be corrected for fluid
      distribution in older populations; this may be a surrogate of muscle quality.
      PURPOSE: Sarcopenia, the age-related loss of muscle mass and function, negatively
      impacts functional status, quality of life, and mortality. We aimed to determine
      if bioimpedance spectroscopy (BIS)-derived estimates of body water compartments
      can be used in conjunction with dual-energy X-ray absorptiometry (DXA) measures
      to aid in the prediction of functional status and thereby, ultimately, improve
      the diagnosis of sarcopenia. METHODS: Participants (>= 70 years) had physical and
      muscle function tests, DXA, and BIS performed. Using a BMI correction method,
      intracellular water (ICWc), extracellular water (ECWc), and ECWc to ICWc (E/Ic)
      ratio was estimated from standard BIS measures. Jump power was assessed using
      jump mechanography. RESULTS: The traditional measure used to diagnose sarcopenia,
      DXA-derived appendicular lean mass (ALM) corrected for height (ALM/ht2), was the
      least predictive measure explaining jump power variability (r2 = 0.31, p <
      0.0001). The best measure for explaining jump power was a novel variable
      combining DXA ALM and BIS-derived E/Ic ratio (ALM/(E/Ic); r2 = 0.70, p < 0.0001).
      ALM/(E/Ic) and ICWc had the highest correlation with jump power and grip
      strength, specifically jump power (r = 0.84 and r = 0.80, respectively; p <
      0.0001). CONCLUSIONS: The creation of a novel variable (ALM/(E/Ic)) improved the
      ability of DXA to predict jump power in an older population. ALM/(E/Ic)
      substantially outperformed traditional lean mass measures of sarcopenia and could
      well be an improved diagnostic approach to predict functional status. DXA
      measured ALM should be corrected for fluid distribution, i.e., ALM/(E/Ic); this
      correction may be considered a surrogate of muscle quality.

PMID- 30218262
TI  - The use of surgical rating scales for the evaluation of surgical working
      conditions during laparoscopic surgery: a scoping review.
AB  - INTRODUCTION: Surgical rating scales (SRSs) enable the surgeon to uniformly
      quantify surgical working conditions. They are increasingly used as a primary
      outcome in studies evaluating the effect of anaesthesia or surgery-related
      interventions on the quality of the surgical work field. SRSs are especially used
      in laparoscopic surgery due to a renewed interest in deep neuromuscular block.
      There are however no guidelines regarding the uniform use of SRS and the uniform
      reporting of results. METHODS: A systematic search was conducted in the databases
      of PubMed, Web of Science and Embase for studies that reported the use of an SRS
      to evaluate surgical conditions in laparoscopic surgery. Only original human
      research in English language with full text availability through the Leiden
      university library was considered for this review. The full texts of eligible
      abstracts were independently reviewed by the first and second author. The quality
      of SRSs and methodology of rating were systematically reviewed. RESULTS: The
      search yielded 2830 reports, of which 17 were identified using a surgical rating
      scale (SRS) in laparoscopic surgery. Ten of these reports used a unique SRS,
      these were systematically appraised for their quality. The overall quality of the
      SRSs was low: the majority of the scales were poorly described and lacked
      assessment of inter- and intra-rater reliability. In addition, considerable
      differences exist in the methodology of rating and the reporting of results.
      CONCLUSION: There is substantial inconsistency in SRS quality, methodology, and
      results reporting. The uniform use of high-quality surgical rating scales is
      needed to improve the quality and reproducibility of future research.

PMID- 30218263
TI  - Robot-assisted versus laparoscopic single-incision cholecystectomy: results of a
      randomized controlled trial.
AB  - BACKGROUND: Although single-port laparoscopic cholecystectomy (SILC) is safe and
      effective, inherent surgeons' discomfort has prevented a large-scale adaptation
      of this technique. Recent advances in robotic technology suggest that da Vinci
      Single-SiteTM cholecystectomy (dVSSC) may overcome this issue by reducing the
      stress load of the surgeon compared to SILC. However, evidence to objectively
      assess differences between the two approaches is lacking. METHODS: 60 patients
      [36 women, 24 men (mean age 52 years)] with benign gallbladder disease were
      randomly assigned to dVSSC (n = 30) or SILC (n = 30) in this single-centre,
      single-blinded controlled trial. The primary endpoint was surgeon's stress load.
      Secondary endpoints included operating time, conversion rates, additional trocar
      placement, blood loss, length of hospital stay, procedure costs, health-related
      quality of life, cosmesis and complications. Data were collected preoperatively,
      during the hospital stay, and at 1 and 12 months' follow-up. RESULTS: The dVSSC
      group showed a significant reduction of mental stress load of the surgeon
      compared to SILC [Subjective Mental Effort Questionnaire (SMEQ) score: median
      25.0 (range 8-89) vs. 42.5 (range 13-110) points; p = 0.002] and a trend towards
      reduced physical stress load [Local Experienced Discomfort (LED) score: median 8
      (range 2-27) vs. 12 (range 0-64) points; p = 0.088]. The length of hospital stay
      was longer in the SILC group [mean 3.06 (median 2; range 1-26) vs. 1.9 (median 2;
      range 1-4) days, p = 0.034] but overall hospital costs were higher for dVSSC
      [median 9734 (range 5775-16729) vs. 6900 (range 4156-99977) CHF; p = 0.001].
      There were no differences in the rate of postoperative complications that
      required re-intervention (Dindo-Clavien grade >= IIIa; SILC n = 2 vs. dVSSC n =
      0, p = 0.492) or other secondary endpoints. CONCLUSIONS: Da Vinci Single-SiteTM
      cholecystectomy provides significant benefits over Single-Port Laparoscopic
      Cholecystectomy in terms of surgeon's stress load, matches the standards of the
      laparoscopic single-incision approach with regard to patients' outcomes but
      increases expenses. Clinicaltrials.gov registration-No.: NCT02485392.

PMID- 30218264
TI  - Impact of Porous Excipients on the Manufacturability and Product Performance of
      Solid Self-Emulsifying Drug Delivery Systems.
AB  - FDA-approved self-emulsifying medicines rely on liquid-based formulations, which
      can exhibit limited stability and short shelf-lives. Solid self-emulsifying drug
      delivery systems (SEDDS) can improve such issues, but there is still a great need
      for identifying suitable porous carriers to convert liquid SEDDS into solids
      without impairing their mechanical properties, functionality, and industrial
      feasibility. The impact of SEDDS adsorption on tableting is also poorly
      understood. Therefore, solid SEDDS were prepared by adsorbing liquid SEDDS onto
      ten commercially available porous excipients. Products were assessed with respect
      to mechanical behavior, tabletability, and product performance. Adsorbing SEDDS
      onto porous excipients led to satisfactory stability, with the exception of
      Zeopharm(r) 600 due to its high alkalinity, and Neusilin(r) US2/UFL2, which
      caused quercetin to crystallize out of the liquid concentrate. SEDDS adsorption
      reduced the elastic recovery of most excipients, making tableting achievable
      using Aeroperl(r) 300 and Aerosil(r) 200/300. The impact of SEDDS on elastic
      recovery provides additional understanding on solid SEDDS manufacture process.
      Acceptable tablets were made via direct compression but with slow disintegration.
      Addition of a superdisintegrant (crospovidone 5% w/w) ensured tablet
      manufacturing without impairment of product performance. Solid SEDDS displayed
      several technical advantages over their liquid counterparts, but attention must
      be given to the properties of the porous excipient chosen. Drug-excipient
      interactions play a significant role in drug degradation and crystallization in
      solid SEDDS. Improved mechanical behavior upon adsorption led to well-composed
      tablets that performed satisfactorily in vitro upon addition of a
      superdisintegrant. This study provides an insight on excipient-oriented rational
      development of solid SEDDS.

PMID- 30218265
TI  - Optimization and Characterization of Thymoquinone-Loaded Liposomes with Enhanced
      Topical Anti-inflammatory Activity.
AB  - Thymoquinone, the major constituent of Nigella sativa oil has been found to have
      a promising topical anti-inflammatory activity; however, exaggerated heat and
      photo-sensitivity and lipophilicity prevent the best use of this promising
      product. The present work aimed to formulate an ideal thymoquinone liposomal
      system for topical delivery. Different liposomal systems were developed using
      thin film hydration method by applying different cholesterol molar
      concentrations, different total lipid molar concentrations, and different drug-to
      lipid ratios. Morphological characterization of the prepared formulae was
      performed using polarized light, scanning electron microscope, and transmission
      electron microscope. The optimized formula (F12) was selected on the basis of
      enhanced permeation through the skin and was incorporated into chitosan gel for
      topical application. The gel formulation was clear with suitable skin permeation
      and exhibited acceptable rheological properties. Using carrageenan-induced paw
      edema in rats, the developed chitosan gel (F12) showed significant superior in
      vivo anti-inflammatory activity over the chitosan gel of the TQ (p < 0.05) and
      comparable effect to the marketed indomethacin gel. As a conclusion, results
      revealed the potential of formulating thymoquinone as liposomal formulation in
      enhancing the anti-inflammatory effect compared to the TQ solution.

PMID- 30218266
TI  - Comparative Study for Optimization of Pharmaceutical Self-Emulsifying Pre
      concentrate by Design of Experiment and Artificial Neural Network.
AB  - The present investigation aimed to optimize the critical parameters affecting the
      globule size of self-emulsifying drug delivery system. Based on preliminary
      screening, three critical parameters, viz., amount of oil, surfactant, and co
      surfactant were found to affect the globule size. I-optimal mixture design and
      Artificial Neural Network (ANN) were used to optimize the formulation with
      respect to minimum globule size. Comparative study was carried out to identify
      which optimization technique gave better predictability for the selected output
      parameter. R-value and MSE values were taken into consideration for comparison of
      both techniques. Using Response Surface Methodology-based I-optimal mixture
      design approach, the R2 value was found to be 0.9867, whereas with ANN technique,
      it was found to be 0.99548. The predicted size for the optimized batch by I
      optimal design was 122.377 nm, whereas by ANN, it was 119.6783 nm against the
      actual obtained size of 118.2 +/- 2.3 nm. This analysis indicated superior
      predictability of output for given input variables by ANN as compared to model
      dependent DoE I-optimal design approach.

PMID- 30218267
TI  - Development of Hot Melt Extruded Solid Dispersion of Tamoxifen Citrate and
      Resveratrol for Synergistic Effects on Breast Cancer Cells.
AB  - Primary standard therapy for ER-positive breast cancer being tamoxifen, newer
      delivery approach for enhancement of dissolution and therapeutic efficiency of
      tamoxifen through oral route could be a possible solution. In the present study,
      we investigated combination of tamoxifen (TAM) with resveratrol (RES) and
      observed that the combination is effective on MCF-7 breast cancer cells. To
      ensure co-delivery of the drugs, we explored the hot melt extrusion technique for
      simultaneously extruding two drugs together in order to enhance their
      bioavailability. As both are class II drugs with dissolution limited
      bioavailability, detailed formulation and process parameter analyses were carried
      out. Detailed characterization using microscopy, Fourier transform infrared
      spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder
      diffraction (XRD) confirmed that both the drugs were molecularly dispersed in the
      matrix of Soluplus, CremophorRH40, and Poloxamer188, and no interactions between
      the ingredients were there during hot melt extrusion (HME) process. Dissolution
      studies confirmed that HME extrudates were able to release drug more rapidly than
      simple suspension formulation. Further, pharmacokinetic studies in rats were
      carried out for tamoxifen. Results demonstrated that extrusion significantly
      increased the tamoxifen oral bioavailability (p < 0.05) (Tmax = 2.00 +/- 0.56 h,
      Cmax = 3.66 +/- 1.49 MUg/mL, AUC = 39.80 +/- 16.24 MUg h/mL, MRT = 20.49 +/-
      5.71) compared to the conventional suspension of tamoxifen (Tmax = 2.00 +/- 0.71
      h, Cmax = 2.41 +/- 0.84 MUg/mL, AUC = 12.82 +/- 3.99 MUg h/mL, MRT = 18.24 +/-
      5.95 h). In vitro cytotoxicity studies of TAM, RES, and their combination (TAM
      RES) were evaluated with MCF7 cells. The combination showed significantly lower
      IC50 compared to TAM with increasing ratio of RES which is a result of apoptosis.
      HME-based simultaneous extrusion of TAM and RES formulation provides a suitable
      formulation strategy for breast cancer treatment and establishes proof of concept
      for extruding multiple drugs simultaneously for other applications in future.

PMID- 30218268
TI  - From waste to resource: A systems dynamics and stakeholder analysis of phosphorus
      recycling from municipal wastewater in Europe.
AB  - Recycling Phosphorus (P) from urban wastewater can secure part of domestic
      agricultural P supply and contribute to a circular P supply chain. In this paper,
      we use literature review, stakeholder interviews and analysis, and systems
      dynamics for the capital cities of Stockholm and Budapest as case studies. We
      find that political support is a prerequisite for developing the P recycling
      sector, and policy makers are the most influential stakeholders. P criticality is
      the main driver for political support. P externalities from mining to sludge
      disposal should be considered when evaluating P criticality and recycling
      profitability. We conclude with policy recommendations for the development of the
      P recycling sector, arguing for legally binding P recycling targets and
      prioritization of the safest technological solutions available. Our analysis
      identifies three policy action indicators and five policy interventions in the
      recycling system.

PMID- 30218269
TI  - Water-energy sustainability synergies and health benefits as means to motivate
      potable reuse of coalbed methane-produced waters.
AB  - Management of coalbed methane (CBM)-produced water is a crucial part of the water
      energy nexus, especially as CBM is projected to play a key role as a bridge fuel
      in major economies. In this paper, we consider one management technique, i.e.,
      desalination of CBM-produced water to generate potable water. We discuss a
      confluence of geographic, sociotechnical, regulatory, and other circumstances
      that could make this concept viable for select coal-bearing regions. Having said
      that, for maximizing benefits, it is prudent to take a synergistic view targeting
      multiple objectives (water access, health, environmental impacts, and ease of
      waste management). Thus, we make design recommendations and suggest a system
      evaluation framework for making sustainable decisions related to produced-to
      potable water systems. For instance, a key question is whether such systems
      should be centralized or decentralized-and this paper highlights crucial
      tradeoffs that are present in both the cases.

PMID- 30218270
TI  - Navigating cognition biases in the search of sustainability.
AB  - We provide a conceptual review of the available knowledge on the role of human
      cognition biases for sustainability and sustainable behavior. Human cognition
      biases are defined as any deviation in decision making from the standard
      framework of rational choice. We distinguish between biases in individual
      decision making and biases in group decision making, and highlight the relevance
      of each for sustainable behavior. We find that while both categories may
      contribute to unsustainable behavior, human cognition biases in group settings
      might be central to understanding many of the current sustainability issues.
      Moreover, we argue that the effects of group-related biases may outweigh those on
      the individual level in driving unsustainable behavior, and that biases that have
      been discussed under various labels in the literature can be interpreted as
      manifestations of human cognition biases in group settings.

PMID- 30218271
TI  - Reverse correlations of collagen-dependent platelet aggregation and adhesion with
      GPVI shedding during storage.
AB  - Platelet receptor GPVI plays an important role in platelet firm adhesion to site
      of vascular injury. Receptor ligation with collagen, in company with other
      agonist/receptor interactions, augments inside out signaling pathways leading to
      platelet aggregation and thrombus formation. As GPVI expression is significantly
      modulated by ectodomain shedding, this study aimed to examine whether GPVI
      shedding functionally affects collagen-mediated platelet activation during
      storage. 6 PRP-platelet concentrates were subjected to adhesion analysis on
      collagen matrix under mild stirring condition as well as collagen-induced
      aggregation on day 1, 3 and 5 post-storage. Concurrently, platelet supernatants
      of same samples were fractionated by ultra-centrifugation and obtained micro
      particle-free samples were subjected to western blot analysis for the evaluation
      of GPVI shedding. We showed a direct correlation between collagen-dependent
      platelet aggregation and adhesion (r = 0.8, p = 0.0001). The increasing levels of
      GPVI shedding during storage were in reverse correlation with collagen-induced
      platelet aggregation (r = - 0.82, p = 0.0004) which was significantly reducing
      during storage. Platelet adhesion to collagen matrix significantly decreased post
      storage while it was also reversely correlated with the levels of GPVI shedding
      during 5 days storage of platelets (r = - 0.69, p = 0.002). Data presented here
      demonstrated that progressive shedding of surface adhesion receptor GPVI can
      affect its functional activities in stored platelets. Thereby considering the
      crucial role of GPVI in platelet adhesion to the site of injury, whether the
      therapeutic efficacy of banked platelet products could be influenced by storage
      dependent shedding of this receptor, remains to be answered in future studies.

PMID- 30218272
TI  - The impact of co-morbidity on the disease burden of VTE.
AB  - Venous thromboembolism (VTE) is often accompanied by co-morbidities, which
      complicate and confound data interpretation concerning VTE-related mortality,
      costs and quality of life. We aimed to assess the contribution of co-morbidities
      to the burden of VTE. The PREFER in VTE registry, across seven European
      countries, documented and followed acute VTE patients over 12 months. Patients
      with co-morbidities were grouped in major co-morbidity groups: cancer,
      cardiovascular (CV) comorbidity (other than VTE), CV risks, venous, renal, liver,
      respiratory, bone and joint diseases, and lower extremity paralysis. Mortality
      rates and health-related quality of life (HrQoL) utility values grouped per co
      morbidity were compared to the UK general population. Regression analyses were
      performed to determine the impact of co-morbidities on mortality and HrQoL. VTE
      were analyzed together and separately as pulmonary embolism (PE) and deep vein
      thrombosis (DVT). In total, 3455 patients were included, 40.5% with PE and 59.5%
      with DVT. 13% and 16% of the PE and DVT patients had no co-morbidities and had a
      12-month mortality rate of 1.8% and 1.7%, respectively. Frequency and severity of
      co-morbidities increased mortality rates up to 30%. The EQ-5D-5L index in
      patients without co-morbidities were 0.826 and 0.838 for PE and DVT. These scores
      decreased to 0.638 and 0.555 in the presence of co-morbidities. Co-morbidities in
      VTE patients are common. VTE had an impact on mortality and HrQoL, and additional
      impact of co-morbidities was seen. Awareness of the presence of co-morbidities is
      important when making VTE-related treatment decisions. The presence of co
      morbidities in PE and DVT patients is common and their frequency and severity in
      VTE patients have a substantial impact on mortality rates and HrQoL. When
      adjusting for co-morbidities, the impact of VTE on mortality as well as health
      related quality of life remains present. Assessing patients without consideration
      of co-morbidities might lead to misinterpretations of the disease burden of PE
      and DVT.

PMID- 30218274
TI  - Gender-Based Occupational Segregation and Sex Differences in Sensory, Motor, and
      Spatial Aptitudes.
AB  - Research on sex differences in humans documents gender differences in sensory,
      motor, and spatial aptitudes. These aptitudes, as captured by Dictionary of
      Occupational Titles (DOT) codes, predict the occupational choices of men and
      women in the directions indicated by this research. We simulate that eliminating
      selection on these skills reduces the Duncan index of gender-based occupational
      segregation by 20 % to 23 % in 1970 and 2012, respectively. Eliminating selection
      on DOT variables capturing other accounts of this segregation has a smaller
      impact.

PMID- 30218275
TI  - Destroyed by Slavery? Slavery and African American Family Formation Following
      Emancipation.
AB  - This study introduces a new sample that links people and families across 1860,
      1880, and 1900 census data to explore the intergenerational impact of slavery on
      black families in the United States. Slaveholding-the number of slaves owned by a
      single farmer or planter-is used as a proxy for experiences during slavery. Slave
      family structures varied systematically with slaveholding sizes. Enslaved
      children on smaller holdings were more likely to be members of single-parent or
      divided families. On larger holdings, however, children tended to reside in
      nuclear families. In 1880, a child whose mother had been on a farm with five
      slaves was 49 % more likely to live in a single-parent household than a child
      whose mother had been on a farm with 15 slaves. By 1900, slaveholding no longer
      had an impact. However, children whose parents lived in single-parent households
      were themselves more likely to live in single-parent households and to have been
      born outside marriage.

PMID- 30218277
TI  - Evolutionary Rescue in a Linearly Changing Environment: Limits on Predictability.
AB  - Populations subject to substantial environmental change that decreases absolute
      fitness (expected number of offspring per individual) to less than one must adapt
      to persist. The probability of adaptive evolutionary rescue may be influenced by
      factors intrinsic to the organism itself, or by features specific to the
      individual population and its environment. An important question (given the
      increasing prevalence of environmental change) is the predictability of
      evolutionary rescue. We used an individual-based simulation model and a related
      analytic model to examine population persistence, given a continuously changing
      environment that leads to a linear change in the optimum for a phenotypic trait
      under selection. Population persistence was not well predicted by the population
      genetics at the start of environmental change, which contrasts strongly with the
      results shown in prior work for persistence after a sudden environmental change.
      Larger populations, which had a greater scope for the generation and maintenance
      of beneficial genetic variation, showed a clear advantage, but increasing the
      rate of environmental change always decreased the probability of persistence.
      Extinctions occurred throughout the period of continuous change, and populations
      that went extinct showed little sign of their eventual fate until shortly before
      extinction. Partially clonal populations showed less predictability and greater
      vulnerability to extinction when impacted by continuous change than did fully
      sexual populations-any advantage gained by the initial transmission of well
      adapted phenotypes via clonal reproduction is lost as the phenotypic optimum
      continues to shift and the generation of novel variation is required for
      continuous adaptation.

PMID- 30218276
TI  - Systematic review of pre-clinical chronic myeloid leukaemia.
AB  - BACKGROUND: Studies of a provisional entity pre-clinical chronic myeloid
      leukaemia (CML), which precedes chronic phase (CP) without leucocytosis or
      blood/marrow feature of CML CP, has been increasing. OBJECTIVE: To perform a
      systematic review of pre-clinical CML and analysis the data relevant to disease
      progression to CML CP. METHOD: We performed a literature search on 16 July 2017
      using EBSCOhost Research Databases interface and Western Pacific Region Index
      Medicus. Two authors selected the studies, extracted the data and evaluated the
      quality of studies using an 8-item tool, independently. The outcomes were
      percentage of Philadelphia chromosome in the number of metaphases examined (Ph%),
      correlation between Ph% and blood count and time progress to CML. RESULT: Our
      initial search returned 4770 studies. A total of 10 studies with a total 17
      subjects were included. The lowest Ph%, which eventually progresses to CML, was
      10%. Absolute basophil count seemed to correlate better with Ph% compared to
      total white cell and absolute eosinophil count. The time from the first
      documented pre-clinical CML to CML ranged from 12 to 48 months. The overall
      quality of the included studies was average. CONCLUSION: This is the first
      systematic review on pre-clinical CML. This entity requires additional large
      scale studies.

PMID- 30218278
TI  - A Multiscale Agent-Based Model for the Investigation of E. coli K12 Metabolic
      Response During Biofilm Formation.
AB  - Bacterial biofilm formation is an organized collective response to biochemical
      cues that enables bacterial colonies to persist and withstand environmental
      insults. We developed a multiscale agent-based model that characterizes the
      intracellular, extracellular, and cellular scale interactions that modulate
      Escherichia coli MG1655 biofilm formation. Each bacterium's intracellular
      response and cellular state were represented as an outcome of interactions with
      the environment and neighboring bacteria. In the intracellular model, environment
      driven gene expression and metabolism were captured using statistical regression
      and Michaelis-Menten kinetics, respectively. In the cellular model, growth,
      death, and type IV pili- and flagella-dependent movement were based on the
      bacteria's intracellular state. We implemented the extracellular model as a three
      dimensional diffusion model used to describe glucose, oxygen, and autoinducer 2
      gradients within the biofilm and bulk fluid. We validated the model by comparing
      simulation results to empirical quantitative biofilm profiles, gene expression,
      and metabolic concentrations. Using the model, we characterized and compared the
      temporal metabolic and gene expression profiles of sessile versus planktonic
      bacterial populations during biofilm formation and investigated correlations
      between gene expression and biofilm-associated metabolites and cellular scale
      phenotypes. Based on our in silico studies, planktonic bacteria had higher
      metabolite concentrations in the glycolysis and citric acid cycle pathways, with
      higher gene expression levels in flagella and lipopolysaccharide-associated
      genes. Conversely, sessile bacteria had higher metabolite concentrations in the
      autoinducer 2 pathway, with type IV pili, autoinducer 2 export, and cellular
      respiration genes upregulated in comparison with planktonic bacteria. Having
      demonstrated results consistent with in vitro static culture biofilm systems, our
      model enables examination of molecular phenomena within biofilms that are
      experimentally inaccessible and provides a framework for future exploration of
      how hypothesized molecular mechanisms impact bulk community behavior.

PMID- 30218279
TI  - To Care and to Provide Care.

PMID- 30218280
TI  - The significant value of predicting prognosis in patients with colorectal cancer
      using 18F-FDG PET metabolic parameters of primary tumors and hematological
      parameters.
AB  - OBJECTS: The purpose was to evaluate the correlation of the pre-treatment
      hematological parameters with metabolic parameters of primary tumor in baseline
      18F-FDG PET/CT in patients with colorectal cancer (CRC) and estimate the
      prognostic value of both. METHODS: We retrospectively investigated 231 patients
      with CRC who underwent baseline 18F-FDG PET/CT. Routine blood sampling was tested
      in the same term. PET parameters in term of hematological parameters and
      pathological characteristics of primary tumor were compared. Kaplan-Meier
      survival analysis was performed in the patients without distant metastasis. The
      differences of disease-free survival between groups were compared by log-rank
      tests. RESULTS: Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte
      ratio (LMR) were significantly correlated with all the metabolic parameters
      including maximum standardized uptake value (SUVmax), metabolic tumor volume
      (MTV) and tumor lesion glycolysis (TLG). The patients with NLR > 3 had higher MTV
      (24.82 +/- 18.16 vs 19.06 +/- 13.30, P = 0.039) and TLG (219.04 +/- 186.94 vs
      166.45 +/- 146.39, P = 0.047) than those whose NLR <= 3. NLR in those patients
      with distant metastasis was significantly higher than those without distant
      metastasis (P = 0.018) while LMR in those patients with distant metastasis was
      significantly lower than those without distant metastasis (P = 0.032). Survival
      analysis showed that those patients with low MTV (P = 0.015), low NLR (P = 0.008)
      and high LMR (P = 0.027) revealed significant survival benefit. CONCLUSIONS:
      There was a significant association between the pre-treatment hematological
      parameters and metabolic parameters of baseline 18F-FDG PET/CT in the patients
      with CRC. It might be helpful in those patients with high NLR and low LMR to
      undergo 18F-FDG PET/CT to detect distant metastasis and predict prognosis.

PMID- 30218281
TI  - Advantages of 99mTc-3PRGD2 SPECT over CT in the preoperative assessment of lymph
      node metastasis in patients with esophageal cancer.
AB  - BACKGROUND: Our study was designed to compare the diagnostic efficacies of
      integrated 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single-photon
      emission computed tomography (SPECT) images and computed tomography (CT) images
      in lymph node metastasis in the patients with esophageal cancer. METHODS: From
      September 2015 and May 2018, 32 patients with histologically proven primary
      esophageal carcinoma underwent both 99mTc-3PRGD2 SPECT and CT scans followed by
      esophagectomy with lymph node dissection. The results of reviewing 99mTc-3PRGD2
      SPECT and CT images for the lymph node metastasis were compared in relation with
      pathologic findings. RESULTS: During surgery, a total of 168 lymph nodes were
      dissected in 32 patients, of which 42 node groups in 18 patients were malignant
      on histologic examination. Preoperative nodal staging was compared with
      postoperative histopathological staging, The sensitivity, specificity, accuracy,
      positive predictive value, and negative predictive value of 99mTc-3PRGD2 SPECT
      for lymph nodes were 80.95%, 86.51%, 85.12%, 66.67%, and 93.16% on per-node
      basis, respectively; compared with 59.52%, 73.02%, 69.64%, 42.37%, and 84.40% for
      CT (p = 0.034, 0.008, 0.005, 0.011, and 0.038, respectively). 70.59% (12/17)
      false-negative interpretations and 50% (17/34) false-positive interpretations on
      CT were corrected by 99mTc-3PRGD2 SPECT. 37.5% false-negative interpretations on
      99mTc-3PRGD2 SPECT were corrected by CT. 11.90% (5/42) positive lymph nodes and
      13.49% (17/126) negative nodes at pathology were incorrectly diagnosed both by
      99mTc-3PRGD2 SPECT and CT. The accuracy of 99mTc-3PRGD2 SPECT (87.50%, 28/32) was
      significantly higher than that of CT (62.50, 20/32; p = 0.022) on per-patient
      basis. 99mTc-3PRGD2 SPECT showed significantly higher sensitivity and accuracy in
      the neck and upper thoracic regions than CT. For nodal staging, 99mTc-3PRGD2
      SPECT was correct in 78.12% (25/32) of the patients, whereas CT was correct in
      53.12% (17/32), p = 0.037. CONCLUSION: 99mTc-3PRGD2 SPECT is more accurate than
      CT for preoperative assessment of lymph node metastasis in esophageal cancer and
      may be helpful in determining the therapeutic plan.

PMID- 30218283
TI  - Pharmacological Modulation of Vagal Nerve Activity in Cardiovascular Diseases.
AB  - Cardiovascular diseases are life-threatening illnesses with high morbidity and
      mortality. Suppressed vagal (parasympathetic) activity and increased sympathetic
      activity are involved in these diseases. Currently, pharmacological interventions
      primarily aim to inhibit over-excitation of sympathetic nerves, while vagal
      modulation has been largely neglected. Many studies have demonstrated that
      increased vagal activity reduces cardiovascular risk factors in both animal
      models and human patients. Therefore, the improvement of vagal activity may be an
      alternate approach for the treatment of cardiovascular diseases. However, drugs
      used for vagus nerve activation in cardiovascular diseases are limited in the
      clinic. In this review, we provide an overview of the potential drug targets for
      modulating vagal nerve activation, including muscarinic, and beta-adrenergic
      receptors. In addition, vagomimetic drugs (such as choline, acetylcholine, and
      pyridostigmine) and the mechanism underlying their cardiovascular protective
      effects are also discussed.

PMID- 30218282
TI  - Preventing Type 2 Diabetes with Home Cooking: Current Evidence and Future
      Potential.
AB  - PURPOSE OF REVIEW: Various dietary regimes have proven effective in preventing
      diabetes, yet its prevalence is growing. This review's goals are to examine the
      relationship between home cooking and diabetes and to present the literature on
      home cooking education programs as a novel strategy to improve adherence to
      healthy nutrition, thus decreasing the risk of diabetes. RECENT FINDINGS:
      Consumption of home-cooked food is linked to healthier nutrition and decreased
      risk of diabetes. Further, home cooking interventions have a short-term positive
      impact on nutritional intake of both children and adults, and on diabetes
      prevention. Well-designed randomized controlled studies are needed to rigorously
      evaluate the long-term impact of home cooking interventions on cooking behavior,
      dietary intake, diabetes, and healthcare costs. Culinary education is an emerging
      field that aims to change nutrition education paradigms. Clinicians can empower
      patients to adopt home cooking by role modeling home cooking themselves,
      including home cooking content in their medical encounters, and through
      comprehensive lifestyle medicine interventions.

PMID- 30218284
TI  - SUMOylation of Fragile X Mental Retardation Protein: A Critical Mechanism of FMRP
      Mediated Neuronal Function.

PMID- 30218285
TI  - Retrovirus-Mediated Transfection of the Tissue-type Plasminogen Activator Gene
      Results in Increased Thrombolysis of Blood Clots.
AB  - Tissue-type plasminogen activator (tPA) is involved in the lysis of blood clots.
      In this study, we attempted to target thrombolysis and enhance blood clot lysis
      by generating a construct (pLEGFP-N1-tPA) to integrate tPA gene into the genome
      of different cell lines. pLEGFP-N1-tPA construct was generated and used to target
      the tPA gene in different cell lines. The thrombolytic effects mediated by the
      supernatant from transfected HeLa cells and Linx cells were assessed using plasma
      thrombus plates. Furthermore, enhanced green fluorescent protein (EGFP), which
      was fused to the tPA gene in the pLEGFP-N1-tPA construct, was analyzed under the
      fluorescent microscope to assess tPA localization. We also monitored tPA activity
      and expression in the transfected cell lines. As part of the study, we
      successfully generated the pLEGFP-N1-tPA construct. The sequence of this
      construct was verified and the construct was subsequently used to generate the
      PT67/pLEGFP-N1-tPA cell line. The pLEGFP-N1-tPA construct was also used to
      transfect HeLa cells and Linx cells. We observed that supernatants from
      transfected cells were capable of lysing thrombi. In addition, tPA activity and
      tPA concentration were elevated in the latter supernatants and tPA was rapidly
      and stably expressed in the transfected cell lines. These results reveal a
      potentially important thrombolytic role for tPA-targeted gene therapy following
      cardiac valve replacement.

PMID- 30218287
TI  - Mycophenolate mofetil treatment with or without a calcineurin inhibitor in
      resistant inflammatory myopathy.
AB  - To evaluate the efficacy and tolerability of mycophenolate mofetil (MMF) with or
      without calcineurin inhibitors (CNIs) in patients with inflammatory myopathy
      taking prednisolone, but refractory to conventional immunosuppressive therapy.
      The records of patients with inflammatory myopathy who had previously failed
      treatment with at least one immunosuppressant were retrospectively evaluated. We
      selected patients treated with MMF and divided them into two groups depending on
      whether or not there was concomitant use of CNIs. We investigated the efficacy by
      changes in creatine kinase (CK) levels, forced vital capacity (%FVC),
      prednisolone dose, and high-resolution computed tomography (HRCT) findings.
      Interstitial lung disease (ILD) progression was defined by more than 10% decline
      of %FVC from baseline. We identified 19 patients on MMF treatment. There were
      seven (36.8%) patients on MMF and CNIs, including five on cyclosporine and two on
      tacrolimus. At baseline, no significant difference was seen in the prevalence of
      ILD between patients taking or not taking CNIs (85.7% vs. 75.0%, P = 0.68).
      Improvement in CK was seen in patients treated with CNIs (P = 0.04) but not in
      those without (P = 0.39). No significant improvement in %FVC and HRCT findings
      were found in patients with ILD in either group, and there were no differences in
      death or ILD progression. The combination of CNIs and MMF might be more effective
      for decreasing CK levels than MMF alone. Neither treatment arm had a beneficial
      effect on ILD over a variable observation period.

PMID- 30218286
TI  - The Effects of Probiotic Honey Consumption on Metabolic Status in Patients with
      Diabetic Nephropathy: a Randomized, Double-Blind, Controlled Trial.
AB  - To the best of our knowledge, this study is the first evaluating the effects of
      probiotic honey intake on glycemic control, lipid profiles, biomarkers of
      inflammation, and oxidative stress in patients with diabetic nephropathy (DN).
      This investigation was conducted to evaluate the effects of probiotic honey
      intake on metabolic status in patients with DN. This randomized, double-blind,
      controlled clinical trial was performed among 60 patients with DN. Patients were
      randomly allocated into two groups to receive either 25 g/day probiotic honey
      containing a viable and heat-resistant probiotic Bacillus coagulans T11 (IBRC
      M10791) (108 CFU/g) or 25 g/day control honey (n = 30 each group) for 12 weeks.
      Fasting blood samples were taken at baseline and 12 weeks after supplementation
      to quantify glycemic status, lipid concentrations, biomarkers of inflammation,
      and oxidative stress. After 12 weeks of intervention, patients who received
      probiotic honey compared with the control honey had significantly decreased serum
      insulin levels (- 1.2 +/- 1.8 vs. - 0.1 +/- 1.3 MUIU/mL, P = 0.004) and
      homeostasis model of assessment-estimated insulin resistance (- 0.5 +/- 0.6 vs.
      0.003 +/- 0.4, P = 0.002) and significantly improved quantitative insulin
      sensitivity check index (+ 0.005 +/- 0.009 vs. - 0.0007 +/- 0.005, P = 0.004).
      Additionally, compared with the control honey, probiotic honey intake has
      resulted in a significant reduction in total-/HDL-cholesterol (- 0.2 +/- 0.5 vs.
      + 0.1 +/- 0.1, P = 0.04). Probiotic honey intake significantly reduced serum high
      sensitivity C-reactive protein (hs-CRP) (- 1.9 +/- 2.4 vs. - 0.2 +/- 2.7 mg/L, P
      = 0.01) and plasma malondialdehyde (MDA) levels (- 0.1 +/- 0.6 vs. + 0.6 +/- 1.0
      MUmol/L, P = 0.002) compared with the control honey. Probiotic honey intake had
      no significant effects on other metabolic profiles compared with the control
      honey. Overall, findings from the current study demonstrated that probiotic honey
      consumption for 12 weeks among DN patients had beneficial effects on insulin
      metabolism, total-/HDL-cholesterol, serum hs-CRP, and plasma MDA levels, but did
      not affect other metabolic profiles. http://www.irct.ir : IRCT201705035623N115.

PMID- 30218288
TI  - Red blood cell distribution width as a potential predictor of survival of
      pulmonary arterial hypertension associated with primary Sjogren's syndrome: a
      retrospective cohort study.
AB  - Pulmonary arterial hypertension (PAH) is a severe complication and leading cause
      of mortality in patients with primary Sjogren's syndrome (pSS). This study was to
      investigate the overall survival rates and the utility of red blood cell
      distribution width (RDW) as a potential prognostic factor of pSS-PAH. This cohort
      study retrospectively enrolled 55 patients with pSS-PAH who were followed up at
      the Department of Rheumatology of Peking Union Medical College Hospital (PUMCH)
      between August 2007 and May 2017. The patients were stratified according to the
      level of RDW (<= 15.0 and > 15.0%). Baseline demographics, laboratory results,
      pulmonary function conditions, hemodynamic assessments, and treatment regimens
      were analyzed. Cox proportional hazards regression analysis was used to identify
      whether RDW level is a factor related to adverse outcome. A total of 55 patients
      were recruited, with an average age of 38.9 +/- 9.3 years. Fifty-four were female
      (98.2%), and the average duration at the time of PAH diagnosis was 25.5 +/- 33.2
      months. Higher RDW levels were found in patients who deceased in follow-up (13.8
      +/- 2.6 vs 16.5 +/- 1.6%, p = 0.003) and with higher NYHA classes (13.8 +/- 1.8
      vs 16.5 +/- 2.9%, p < 0.001). Patients with RDW > 15% had a significantly worse
      overall survival than patients with RDW <= 15% (3-year survival rate 59.5 vs.
      88.7% log-rank p = 0.015). Cox regression analysis identified RDW > 15% as a
      prognostic factor for adverse outcome (HR 1.786, 95% CI 1.137-2.803, p = 0.012).
      RDW can serve as a potential negative prognostic factor of pSS-PAH.

PMID- 30218289
TI  - Clinical role of albumin to globulin ratio in microscopic polyangiitis: a
      retrospective monocentric study.
AB  - We investigated whether albumin to globulin ratio (AGR) at diagnosis may be
      associated with all-cause mortality in immunosuppressive drug-naive patients with
      microscopic polyangiitis (MPA). We retrospectively reviewed the medical records
      of 88 MPA patients, who were first classified and in whom medications was first
      initiated in our tertiary Hospital. We collected clinical and laboratory data as
      well as the rate of all-cause mortality. AGR at diagnosis was calculated as a
      ratio of serum albumin over globulin fraction (protein-albumin). We compared
      variables between survived and deceased patients. The multivariable Cox hazard
      model was conducted to appropriately obtain the hazard ratios (HRs). The mean age
      at diagnosis was 56.3 years and 24 patients (27.3%) were men. Seven patients died
      for the mean follow-up period of 49.7 months. Deceased patients were elder than
      survived patients (P = 0.048). Five factor score (FFS) (2009) (P = 0.001),
      creatinine (P = 0.026) and AGR (P = 0.007) at diagnosis in deceased patients were
      higher than those in the survived. In the multivariable Cox hazard model
      analysis, only AGR at diagnosis (HR 0.004) was inversely associated with all
      cause mortality during the follow-up. Furthermore, when the cutoff of AGR for
      death was set as 0.88, patients with AGR <= 0.88 exhibited the lower cumulative
      patients survival rate than those with AGR > 0.88 (P = 0.006). Among the
      conventional and MPA-related risk factors for mortality, AGR at diagnosis is
      inversely associated with all-cause mortality during follow-up in MPA patients.

PMID- 30218290
TI  - The "National Integrated Medical Imaging System" [NIMIS]-friend, not nimesis!
AB  - INTRODUCTION: The "National Integrated Medical Imaging System" or NIMIS went live
      in 2011 and allows the movement of patient radiology imaging throughout the Irish
      health system. At the time of its launch, NIMIS was not only going to allow the
      filmless passage of patient radiology imaging but it was also envisaged that it
      would act as a medical image archive. The aim of this study was to assess the
      awareness and use of non-consultant hospital doctors and hospital consultants
      with regard to this medical image archive/referral function of NIMIS. METHODS: A
      survey was carried out on 50 doctors across all specialities and grades at
      Tullamore Hospital looking at different aspects of the use of NIMIS. RESULTS:
      Ninety-four percent of respondents use NIMIS on a daily basis and 6% use it on a
      weekly basis. The primary reason for using NIMIS was found to be "Viewing and
      Ordering Imaging" in 92% of those surveyed with 8% stating it was "Viewing
      imaging/reports". Ninety-eight percent surveyed said they had never used NIMIS to
      send a referral form or clinical photograph and 82% were not aware of this
      potential function. The majority of those surveyed stated that they either agreed
      or strongly agreed NIMIS is user-friendly. CONCLUSION: NIMIS allows the safe and
      confidential flow of patient images and clinical information in the Irish health
      system. It could provide definite potential in the areas of clinical
      conferencing, multidisciplinary meetings and remote patient assessment along with
      collaborative research and education.

PMID- 30218291
TI  - A systematic review of the clinical effectiveness of emergency endovascular
      therapy using mechanical thrombectomy in acute ischaemic stroke: implications for
      service delivery.
AB  - BACKGROUND: Twelve randomised controlled trials (RCTs) comparing mechanical
      thrombectomy against traditional treatment options for patients experiencing
      acute ischaemic stroke (AIS) have been published. AIMS: To evaluate whether this
      technology is more effective and/or safer than traditional treatment options and
      to assess the potential for implementation of this technology as a treatment
      strategy for acute ischaemic stroke in Ireland. METHODS: RCTs published up to
      February 2017 were included. Meta-analysis was performed for two primary
      (mortality at 90 days, mRS at 90 days) and four secondary outcomes. Cumulative
      meta-analysis was used to investigate the point at which a consistent treatment
      effect was observed for outcomes that had a statistically significant pooled
      effect. RESULTS: Mechanical thrombectomy was associated with higher likelihood of
      being independent (mRS, p < 0.01; Barthel index, p < 0.01) at 90 days post-AIS (p
      < 0.001). Cumulative meta-analysis demonstrated a consistent treatment effect in
      favour of mechanical thrombectomy after each trial was added to the analysis.
      There was no evidence of a difference in mortality rates (p = 0.21) or rates of
      SICH (p = 0.71) between patients randomised to intervention and control arms.
      Although the intervention appears to be associated with higher rates of any
      cerebral haemorrhage (p < 0.01) and recurrent ischaemic stroke (p = 0.03),
      considerable uncertainty remains as to these treatment effects. CONCLUSIONS: The
      trials published most recently have acted as a 'watershed' for mechanical
      thrombectomy, and while there are significant caveats, the data suggests that
      mechanical thrombectomy needs to be factored into the planning and delivery of
      services for the management of patients with acute ischaemic stroke in Ireland.

PMID- 30218292
TI  - Profile of siRNAs derived from green fluorescent protein (GFP)-tagged Papaya leaf
      distortion mosaic virus in infected papaya plants.
AB  - We used green fluorescent protein (GFP)-tagged Papaya leaf distortion mosaic
      virus (PLDMV-GFP) to track PLDMV infection by fluorescence. The virus-derived
      small interfering RNAs (vsiRNAs) of PLDMV-GFP were characterized from papaya
      plants by next-generation sequencing. The foreign GFP gene inserted into the
      PLDMV genome was also processed as a viral gene into siRNAs by components
      involved in RNA silencing. The siRNAs derived from PLDMV-GFP accumulated
      preferentially as 21- and 22-nucleotide (nt) lengths, and most of the 5'-terminal
      ends were biased towards uridine (U) and adenosine (A). The single-nucleotide
      resolution map revealed that vsiRNAs were heterogeneously distributed throughout
      the PLDMV-GFP genome, and vsiRNAs derived from the sense strand were more
      abundant than those from the antisense strand. The hotspots were mainly
      distributed in the P1 and GFP coding region of the antisense strand. In addition,
      979 papaya genes targeted by the most abundant 1000 PLDMV-GFP vsiRNAs were
      predicted and annotated using GO and KEGG classification. Results suggest that
      vsiRNAs play key roles in PLDMV-papaya interactions. These data on the
      characterization of PLDMV-GFP vsiRNAs will help to provide insight into the
      function of vsiRNAs and their host target regulation patterns.

PMID- 30218293
TI  - Evaluation of the serum virome in calves persistently infected with Pestivirus A,
      presenting or not presenting mucosal disease.
AB  - Bovine viral diarrhea virus 1, reclassified as Pestivirus A, causes an
      economically important cattle disease that is distributed worldwide. Pestivirus A
      may cause persistent infection in that calves excrete the virus throughout their
      lives, spreading the infection in the herd. Many persistently infected (PI)
      calves die in the first 2 years of life from mucosal disease (MD) or secondary
      infections, probably as a consequence of virus-induced immune depression. Here,
      high-throughput sequencing (HTS) was applied for evaluation of the total virome
      in sera of (i) PI calves displaying clinically apparent MD (n = 8); (ii) PI
      calves with no signs of MD (n = 8); and (iii) control, Pestivirus A-free calves
      (n = 8). All the groups were collected at the same time and from the same herd.
      Serum samples from calves in each of the groups were pooled, submitted to viral
      RNA/DNA enrichment, and sequenced by HTS. Viral genomes of Pestivirus A, Ungulate
      erythroparvovirus 1, bosavirus (BosV), and hypothetical circular Rep-encoding
      single-stranded DNA (CRESS-DNA) viruses were identified. Specific real-time PCR
      assays were developed to determine the frequency of occurrence of such viruses in
      each of the groups. The absolute number of distinct viral genomes detected in
      both PI calf groups was higher than in the control group, as revealed by higher
      number of reads, contigs, and genomes, representing a wider range of taxons.
      Genomes representing members of the family Parvoviridae, such as U.
      erythroparvovirus 1 and BosV, were most frequently detected in all the three
      groups of calves. Only in MD-affected PI calves, we found two previously
      unreported Hypothetical single-stranded DNA genomes clustered along with CRESS
      DNA viruses. These findings reveal that parvoviruses were the most frequently
      detected viral genomes in cattle serum; its frequency of detection bears no
      statistical correlation with the status of calves in relation to Pestivirus A
      infection, since clinically normal or MD-affected/non-affected PI calves were
      infected with similar U. erythroparvovirus 1 genome loads. Moreover, MD-affected
      PI calves were shown to support viremia of CRESS-DNA viral genomes; however, the
      meaning of such correlation remains to be established.

PMID- 30218294
TI  - Genome-wide association study of heading and flowering dates and construction of
      its prediction equation in Chinese common wheat.
AB  - Heading date is one of the most important traits in wheat breeding as it affects
      adaptation and yield potential. A genome-wide association study (GWAS) using the
      90 K iSelect SNP genotyping assay indicated that a total of 306 loci were
      significantly associated with heading and flowering dates in 13 environments in
      Chinese common wheat from the Yellow and Huai wheat region. Of these, 105 loci
      were significantly correlated with both heading and flowering dates and were
      found in clusters on chromosomes 2, 5, 6, and 7. Based on differences in
      distribution of the vernalization and photoperiod genes among chromosomes, arms,
      or block regions, 13 novel, environmentally stable genetic loci were associated
      with heading and flowering dates, including RAC875_c41145_189 on 1DS,
      RAC875_c50422_299 on 2BL, and RAC875_c48703_148 on 2DS, that accounted for more
      than 20% phenotypic variance explained (PVE) of the heading/flowering date in at
      least four environments. GWAS and t test of a combination of SNPs and
      vernalization and photoperiod alleles indicated that the Vrn-B1, Vrn-D1, and Ppd
      D1 genes significantly affect heading and flowering dates in Chinese common
      wheat. Based on the association of heading and flowering dates with the
      vernalization and photoperiod alleles at seven loci and three significant SNPs,
      optimal linear regression equations were established, which show that of the
      seven loci, the Ppd-D1 gene plays the most important role in modulating heading
      and flowering dates in Chinese wheat, followed by Vrn-B1 and Vrn-D1.
      Additionally, three novel genetic loci (RAC875_c41145_189, Excalibur_c60164_137,
      and RAC875_c50422_299) also show important effect on heading and flowering dates.
      Therefore, Ppd-D1, Vrn-B1, Vrn-D1, and the novel genetic loci should be further
      investigated in terms of improving heading and flowering dates in Chinese wheat.
      Further quantitative analysis of an F10 recombinant inbred lines population
      identified a major QTL that controls heading and flowering dates within the Ppd
      D1 locus with PVEs of 28.4% and 34.0%, respectively; this QTL was also
      significantly associated with spike length, peduncle length, fertile spikelets
      number, cold resistance, and tiller number.

PMID- 30218295
TI  - Linear and Multi-Photon Fluorescence of Thiophene Based Copolymer with Electron
      Accepting Side Chains.
AB  - A novel copolymer poly(thiophene-2,5-diyl-2,5-di-n-octyloxycarbonyl-1,4
      phenylene), denoted as P33, is introduced as potential material for
      photovoltaics, polymer light-emitting diodes, and/or organic transistors. P33
      dissolved in chloroform is investigated by steady-state absorption, linear/non
      linear fluorescence spectroscopies and time-resolved fluorescence spectroscopy.
      Molar extinction coefficient, fluorescence quantum yield, and singlet
      fluorescence lifetime of P33 are determined to be 18,315 M-1 cm-1, 0.4, and 810
      ps, respectively. The P33 fluorescence fast components of decay times are 1.2 ps,
      2.0 ps, and 0.5 ps for increasing wavelengths of 480 nm, 500 nm, and 520 nm,
      respectively. The fast component is attributed to a transport of nearly
      instantaneously formed excitons to localized states known as downhill energy
      transfer. Additionally multi-photon excited fluorescence is observed for pumping
      with wavelengths of 800 nm and 1200 nm. Two-photon absorption cross-section is
      determined to be 6.9 GM. These spectroscopic studies provide basic fluorescence
      characteristics of the novel thiophene copolymer P33.

PMID- 30218297
TI  - Influence of chronic kidney disease and worsening renal function on clinical
      outcomes in patients undergoing primary percutaneous coronary intervention.
AB  - BACKGROUND: The combined influence of CKD and worsening renal function (WRF) on
      clinical outcomes in patients undergoing primary percutaneous coronary
      intervention (PCI) for acute myocardial infarction (AMI) has not been fully
      understood. METHODS: We analyzed 443 patients diagnosed with AMI who underwent
      primary PCI. Based on their estimated glomerular filtration rate (eGFR), they
      were classified into two groups: a high eGFR group (eGFR >= 45 mL/min/1.73 m2, n
      = 381) and a low eGFR group (eGFR < 45 mL/min/1.73 m2, n = 63). WRF was defined
      as an increase in serum creatinine levels >= 0.3 mg/dL above the admission value
      during the course of hospitalization. The primary end-point was set as all-cause
      mortality. RESULTS: WRF was observed in 88 patients (19.8%). The median follow-up
      duration was 769 (interquartile range 397-1314) days. The all-cause mortality
      rate was significantly lower in the high eGFR than in the low eGFR group (5.5 vs.
      28.6%, respectively, at 1500 days, P < 0.001). In patients with WRF, the all
      cause and cardiac mortality rates were significantly higher than in patients
      without WRF, and these results were consistent between the high and low eGFR sub
      groups. Multivariate Cox proportional hazards model analysis showed that low eGFR
      and WRF remained independent predictors of all-cause mortality [(hazard ratio
      2.61, 95% confidence interval 1.27-5.36, P = 0.009) and (hazard ratio 2.59, 95%
      confidence interval 1.34-5.01, P = 0.005), respectively]. CONCLUSIONS: Both eGFR
      at baseline and WRF were observed to be important predictors of mortality in
      patients with AMI undergoing primary PCI. WRF showed a significant effect on
      mortality even in patients with high eGFR.

PMID- 30218296
TI  - The emerging role of lncRNAs in the regulation of cancer stem cells.
AB  - BACKGROUND: Tumors contain a functional subpopulation of cells that exhibit stem
      cell properties. These cells, named cancer stem cells (CSCs), play significant
      roles in the initiation and progression of cancer. Long non-coding RNAs (lncRNAs)
      can act at the transcriptional, posttranscriptional and translational level. As
      such, they may be involved in various biological processes such as DNA damage
      repair, inflammation, metabolism, cell survival, cell signaling, cell growth and
      differentiation. Accumulating evidence indicates that lncRNAs are key regulators
      of the CSC subpopulation, thereby contributing to cancer progression. The aim of
      this review is to overview current knowledge about the functional role and the
      mechanisms of action of lncRNAs in the initiation, maintenance and regulation of
      CSCs derived from different neoplasms. These lncRNAs include CTCF7, ROR, DILC,
      HOTAIR, H19, HOTTIP, ATB, HIF2PUT, SOX2OT, MALAT-1, CUDR, Lnc34a, Linc00617,
      DYNC2H1-4, PVT1, SOX4 and ARSR Uc.283-plus. Furthermore, we will illustrate how
      lncRNAs may regulate asymmetric CSC division and contribute to self-renewal, drug
      resistance and EMT, thus affecting the metastasis and recurrence of different
      cancers. In addition, we will highlight the implications of targeting lncRNAs to
      improve the efficacy of conventional drug therapies and to hamper CSC survival
      and proliferation. CONCLUSIONS: lncRNAs are valuable tools in the search for new
      targets to selectively eliminate CSCs and improve clinical outcomes. LncRNAs may
      serve as excellent therapeutic targets because they are stable, easily detectable
      and expressed in tissue-specific contexts.

PMID- 30218298
TI  - Risk factors for kidney disease among HIV-1 positive persons in the methadone
      program.
AB  - BACKGROUND: Kidney injury is a serious comorbidity among HIV-infected patients.
      Intravenous drug use is listed as one of the risk factors for impaired renal
      function; however, this group is rarely assessed for specific renal-related
      risks. METHODS: Patients attending methadone program from 1994 to 2015 were
      included in the study. Data collected included demographic data, laboratory
      tests, antiretroviral treatment history, methadone dosing and drug abstinence.
      Patients' drug abstinence was checked monthly on personnel demand. We have
      evaluated two study outcomes: (1) having at least one or (2) three eGFR < 60
      ml/min (MDRD formula). RESULTS: In total, 267 persons, with 2593 person-years of
      follow-up were included into analyses. At the time of analyses, 251 (94%) were on
      antiretroviral therapy (ARV). Fifty-two (19.5%) patients had 1eGFR and 20 (7.5%)
      3eGFR < 60. In univariate analysis, factors significantly increasing the odds of
      impaired renal function were: female gender, detectable HIV RNA on ART, age at
      registration per 5 years older, atazanavir use and time on antiretroviral
      treatment per 1 year longer. In the multivariate model, only female gender (OR
      4.7; p = 0.002), time on cART (OR 1.11; p = 0.01) and baseline eGFR (OR 0.71; p =
      0.001) were statistically significant. CONCLUSIONS: We have demonstrated a high
      rate of kidney function impairment among HIV-1 positive patients in the methadone
      program. All risk factors for decreased eGFR in this subpopulation of patients
      were similar to those described for general HIV population with very high
      prevalence in women. These findings imply the need for more frequent kidney
      function monitoring in this subgroup of patients.

PMID- 30218299
TI  - Characterization of a Recombinant Trehalose Synthase from Arthrobacter
      chlorophenolicus and its Unique Kinetics Indicating a Substrate Cooperativity.
AB  - Trehalose is a non-reducing disaccharide with beneficial physiological properties
      and commercial potential. Trehalose synthase (EC 5.4.99.16) catalyzes the
      reversible conversion between maltose and trehalose. A recombinant trehalose
      synthase from Arthrobacter chlorophenolicus SK 33.001 (ACTS) was cloned,
      expressed, and characterized. The recombinant enzyme encoded a protein of 598
      amino acids with a molecular mass of 66 kDa. Gel filtration showed that ACTS is a
      tetramer in sodium phosphate buffer. The enzyme was metal ion independent and
      exhibited maximal activity in sodium phosphate buffer (pH 7.5) at 30  degrees C.
      The kinetic investigations resulted in a KM value of 120.5 +/- 4.5 mM for maltose
      and a KM value of 343.1 +/- 13.8 mM for trehalose. The catalytic efficiency
      (Vmax/KM) for maltose and trehalose were 0.2 and 0.15 U mg-1 mM-1, respectively.
      In addition, a cooperative substrate binding was found displayed by the
      determined Hill coefficients (nH) of 2.8 for maltose and 2.1 for trehalose as a
      substrate, respectively. The final trehalose yield of various maltose
      concentrations (50-1000 mM) was constant between 58 and 59%, implying that
      substrate concentration had no inhibitory influence on ACTS activity.

PMID- 30218300
TI  - pH-Based Detection of Target Analytes in Diluted Serum Samples Using Surface
      Plasmon Resonance Immunosensor.
AB  - Detection of minute quantities of target antigens in serum samples (consisting of
      a mixture of proteins/biomolecules) can be achieved by enhancement of the capture
      efficiencies of heterogeneous immunosensors. An important process parameter which
      affects the capture of target analytes in such immunosensors is the pH of the
      solution as the target proteins present in the serum samples are charged
      molecules. Here, we investigated the capture of prostate-specific antigens
      (PSAs), first in a mixed-analyte system wherein the solution contained two other
      non-specific proteins along with the target analyte, using the surface plasmon
      resonance spectroscopy. There are no reports on the detection of antigens in a
      mixed system based on the optimization of the pH values of the carrier fluid, and
      this is the motivation of the present work. Further, we studied interference
      effects caused by the presence of these non-specific proteins in the mixed
      analyte systems by artificially increasing the ratio of the interfering proteins
      to that of the target protein. Eventually PSA spiked into the rabbit serum
      samples was captured through the optimization of the pH of the solution. We could
      detect PSA in the serum samples when diluted to 100 times or more, where the
      amounts of other interfering proteins were ~ 66 times that of the amount of PSA.
      This study proposes a heterogeneous immunosensor to detect the target analytes in
      the diluted serum samples by tuning pH the of solution mixture, which can be
      utilized to detect disease biomarkers in serum samples.

PMID- 30218301
TI  - Production of Ethyl Esters by Direct Transesterification of Microalga Biomass
      Using Propane as Pressurized Fluid.
AB  - This work aimed to produce ethyl esters from Chlorella vulgaris microalgae
      biomass, using an immobilized enzymatic catalyst associated with pressurized
      fluid (propane) by direct transesterification. In order to optimize the ethyl
      conversion, different temperatures (46.7-68.1  degrees C) and pressures (59.5
      200.5 bar) were applied a central composite design rotational (CCDR) obtaining
      the high conversion (74.39%) at 50  degrees C and 180 bar. The molar ratio also
      was investigated showing conversions ~ 90% using a molar ratio of 1:24
      (oil:ethanol). From the best transesterification conditions, 50  degrees C, 180
      bar, 20% enzymatic concentration, and 1:24 oil:ethanol molar ratio were obtained
      with success 98.9% conversion in 7 h of reaction. The enzyme reuse maintained its
      activity for three successive cycles. Thus, this simple process was effective to
      convert microalgal biomass into ethyl ester by direct transesterification and
      demonstrate high yields.

PMID- 30218302
TI  - Upgrading Pectin Production from Apple Pomace by Acetic Acid Extraction.
AB  - Pectin, as one of the most widely used functional polysaccharide, can be
      abundantly extracted from apple pomace which is the main by-product of apple
      juice industry. In the case of 110 min, 10% (w/w) acetic acid (AA), and 100 
      degrees C, extraction yield of pectin reached 19.6%. Compared with mineral acid
      extracted pectin, the yield, molecular weight, galacturonic acid content, and DE
      of the AA-extracted pectin were higher while neutral sugars were lower.
      Furthermore, the AA-extracted pectin solution demonstrated a higher viscosity
      during the shear rate increased, and a higher G" modulus than pectin extracted
      with mineral acid and commercial pectin possibly because of stronger polymer
      chain interaction, which was reflected in gel textural properties. The green
      approach for the pectin production, in terms of pectin components was developed
      from apple pomace using AA that was highly competitive and environmentally
      friendly process.

PMID- 30218303
TI  - Value of low-dose whole-body CT in the management of patients with multiple
      myeloma and precursor states.
AB  - OBJECTIVE: To determine the value of low-dose whole-body CT (WBCT) in the
      management of patients with multiple myeloma (MM) and precursor states. MATERIALS
      AND METHODS: The study group comprised 116 patients (mean age: 68 +/- 11 years,
      48% women) who underwent WBCT for the work-up or surveillance of MM or MM
      precursor disease. WBCTs were reviewed for the presence of MM-related bone
      disease and incidental findings requiring therapy. The medical records, results
      from bone marrow aspirations and biopsies and follow-up imaging studies were
      reviewed to assess the influence of WBCT on patient management. RESULTS: Whole
      body CT led to a change in management in 32 patients (28%). Of those, 17 patients
      with MM precursor disease were found to have MM-related bone disease, 13 patients
      had progression of MM, requiring a change in treatment, in one patient
      hepatocellular carcinoma was diagnosed, requiring a change in therapy, and one
      patient had a rib lesion requiring intervention. In 65 patients (56%), WBCT was
      performed for surveillance of MM precursor disease or stable treated MM, and did
      not detect new lesions, thereby providing reassurance to the hematologist on
      disease status and management. In 15 patients (13%) WBCT was performed as a new
      baseline before a change or new therapy. In 4 patients (3%), WBCT was performed
      for a change in symptoms, but did not detect lesions that would lead to a change
      in management. CONCLUSION: Whole-body CT provides important information for
      disease monitoring and detection of incidental findings, thereby improving the
      management of patients with MM.

PMID- 30218304
TI  - Surgical and oncological safety of nipple-sparing mastectomy in an Asian
      population.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) allows for excellent postmastectomy
      reconstruction aesthetics and is used for both therapeutic and risk-reducing
      purposes. Reservations regarding the potential for locoregional recurrence and
      concerns about nipple-areolar complex (NAC) necrosis remain amongst many
      surgeons. We review the surgical and oncological outcomes after NSM in our
      institution. METHODS: All NSM cases at the National Cancer Centre Singapore and
      Singapore General Hospital between 2005 and 2015 were reviewed. Tumour
      characteristics, reconstruction methods, surgical and oncological outcomes are
      described. RESULTS: A total of 139 NSMs were performed for 130 patients. The
      median age was 46 years (range 21-66). The use of NSM increased from 2% of all
      breast reconstructions in 2005 to 37% in 2015. The majority (n = 119; 86%) were
      for cancer treatment and 20 (14%) for risk-reducing purposes. Among those
      performed for cancer, patients mainly had early stage breast cancer (n = 106,
      89%). Autologous reconstruction (n = 111, 80%) was most common. Early
      complications requiring surgical intervention occurred in 24 (17%) NSMs,
      including 9 partial/complete flap loss and 2 complete NAC loss. Smoking, previous
      breast radiation and periareolar incision were all not associated with a higher
      re-intervention rate (p = 0.93, 0.41 and 0.91, respectively). Median follow-up
      was 43 months (range 5-145). Five patients (4%) developed local recurrence,
      including 2 NAC recurrences. The 2- and 5-year overall survival rate is 97 and
      90%, respectively. CONCLUSION: NSM is an oncologically safe procedure in selected
      patients with acceptable low complication rates.

PMID- 30218305
TI  - Goal-directed therapy in cytoreductive surgery with hyperthermic intraperitoneal
      chemotherapy: a prospective observational study.
AB  - BACKGROUND: Cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal
      Chemotherapy (HIPEC) in peritoneal carcinomatosis treatment causes significant
      hemodynamic, metabolic, and hematological alterations. Studies on the anesthetic
      intraoperative management are heterogeneous and scarce. There is a great
      heterogeneity in the anesthetic management of CRS and HIPEC. The aim of this
      study is to analyze perioperative hemodynamic goal-directed management and to
      evaluate the complications arisen until the seventh postoperative day. METHODS:
      Prospective, observational study of all CRS and HIPEC patients from March 2014 to
      May 2017. Hemodynamic and clinical parameters were registered during surgery and
      the first 3 postoperative days. We correlated intraoperative data with the
      postoperative course until the seventh day. RESULTS: A total of 92 patients were
      included in the study (age 58.5 +/- 10.9 years, 47% colorectal carcinoma, and 38%
      ovarian carcinoma). Peritoneal Carcinomatosis Index (PCI) (median and ranges) was
      10 [0-39]. Cardiac Index (CI) 3.15 l/min-1/m-2 [1.79-5.60]) and Systolic Volume
      Variation (SVV) (10% [3%-17%]) remained within the values of normality in all
      surgery phases. A large difference was observed between the minimum and maximum
      ranges of fluid therapy administered (median 9.8 ml/kg/h [5.3-24.3]), showing a
      great interindividual variation in the fluids requirement. A direct relationship
      was observed between PCI and surgery duration, fluid therapy, and intraoperative
      transfusion percentage (p < 0.02). CONCLUSIONS: There is a great variability in
      the intraoperative fluid therapy needs of the patients. SVV monitoring makes it
      possible to adjust the fluid therapy needs in each surgery phase. The use of a
      hemodynamic goal-directed anesthetic protocol in CRS and HIPEC enables to
      individually adjust the fluid therapy, avoiding over-hydration and ensuring
      hemodynamic stability in all surgery phases.

PMID- 30218306
TI  - Epithelial membrane protein 2: a novel biomarker for circulating tumor cell
      recovery in breast cancer.
AB  - PURPOSE: EpCAM is a common marker used in the detection of circulating tumor
      cells (CTC). Disseminated cancer cells display the characteristics of epithelial
      to-mesenchymal transition events. The purpose of this study was to assess the
      potential of epithelial membrane protein 2 (EMP2) as a novel biomarker for CTC
      retrieval in breast cancer. METHODS: MCF7 and MDA-MB-231 cells were stained with
      either anti-EpCAM or anti-EMP2 mAbs, respectively, followed by flow cytometric
      assay to measure their expression levels. PBMCs isolated from healthy donors were
      used for breast cancer cell spiking. CD45-depleted PBMCs from breast cancer
      patients' blood were used for CTC capturing. Immunomagnetic separation was used
      to enrich breast cancer cells. Cytospin centrifugation was performed to
      concentrate the captured cells, followed by immunofluorescence staining with anti
      CD45 mAb, anti-pan cytokeratin mAb and DAPI. Fluorescent images were taken using
      a confocal microscope for CTC counts. RESULT: MDA-MB-231 cells had 2.56 times
      higher EMP2 expression than MCF7 cells, and EMP2 had a significantly higher
      capture efficiency than EpCAM for MCF7 cells. Furthermore, anti-EMP2 was capable
      of capturing MCF7 cells that escaped in the flow-through of anti-EpCAM. Likewise,
      EMP2 had a significantly higher capture efficiency on MDA-MB-231 cells when
      compared to MCF7 cells. Most importantly, EMP2 biomarker was successfully used
      for CTC capture in patients with primary breast cancer. CONCLUSIONS: EMP2 is
      superior to EpCAM for capturing both MCF7 and MDA-MB-231 cells. Additionally,
      EMP2 is a novel biomarker and capable of capturing breast cancer cells in patient
      blood samples.

PMID- 30218307
TI  - The role of biomarkers in bladder preservation management of muscle-invasive
      bladder cancer.
AB  - PURPOSE: Patients with localized muscle-invasive bladder cancer (MIBC) can choose
      to undergo either neoadjuvant chemotherapy followed by radical cystectomy or
      radiation therapy-based bladder preservation treatment modality with subsequent
      close cystoscopic surveillance with salvage cystectomy reserved for patients with
      evidence of local disease recurrence. At the present time, the decision regarding
      bladder-directed local therapy for MIBC is based on physicians' and patients'
      preferences, and does not take into account tumor biology. Predictive biomarkers,
      once validated, could offer a more patient-centered and biology-driven selection
      of bladder-directed therapies. METHODS: We provide a narrative review of clinical
      data pertaining to the biomarkers in bladder preservation management of MIBC.
      RESULTS: There are currently no validated and clinically used biological markers
      used for stratification of radical bladder treatment and selection of bladder
      preserving therapies. This article summarizes biomarkers that could have a
      potential clinical utility-PD-L1, molecular subtypes, Ki-67, MRE-11 and markers
      of hypoxia-and offers a hypothetical pathway model for a marker-driven precision
      management of medically operable patients with a newly diagnosed MIBC.
      CONCLUSION: When selecting the optimal cancer treatment, both patient and tumor
      factors need to be considered. Once validated, biological markers will help
      clinicians tailor the management of MIBC to individual patients.

PMID- 30218309
TI  - Nachruf Prof. Dr. med. Georg Peters.

PMID- 30218308
TI  - SIU-ICUD on bladder cancer: pathology.
AB  - Many changes have been made during these last years and concepts for
      understanding bladder cancer have evolved. We make an update with the latest
      findings of the WHO (World Health Organistaion) 2016, ICCR (International
      Collaboration on Cancer Reporting) and other official organisms and try to show
      the latest developments. In this document we provide new consensus guidelines and
      insights. We kept this document short and concise providing consensus guidelines
      to clinicians for the best patient care, it should be easy to understand for a
      non pathologists. We focussed on several burning issues, such as the anatomical
      and histological understanding of the bladder wall, the prognostic significance
      of grading and the most challenging problems in staging, we underline our needs
      from the clinicians such as clinical information, we further discuss the
      histological subtypes of bladder cancer, which is an extremely important issue in
      the light of molecular classifications and give prognostic insights. Furthermore,
      we discuss the ICCR worldwide consensus reporting, urinary cytology with the
      Paris system and several issues such as frozen section specimen.

PMID- 30218310
TI  - Correction to: Mucormycosis in hospitalized patients at a tertiary care center in
      Lebanon: a case series.
AB  - The spelling of the name "Ali Bazarbachi" was incorrect.

PMID- 30218311
TI  - Essentials in Candida bloodstream infection.
AB  - AIMS: Due to the increase of severely immunocompromised patients, of invasive
      procedures including central intravascular catheters, and of the use of broad
      spectrum antibiotics, the incidence of Candida bloodstream infections has risen
      intensely in the last decades. Candida bloodstream infection is a serious disease
      with high mortality. Optimized diagnostic and therapeutic management can improve
      outcome. Thus, the aim of our mini-review is to highlight important and often
      missed opportunities in the management of Candida bloodstream infection. METHODS:
      We searched the published literature and describe the essentials in the
      management of Candida bloodstream infection. RESULTS: Four essentials were
      identified: (1) isolation of Candida spp. from a blood culture should always be
      considered relevant and requires treatment. Daily blood cultures should be drawn
      to determine cessation of candidemia. (2) Central venous catheter (CVC) and/or
      other indwelling devices should be removed. (3) Echinocandins are the first
      choice. Antifungal treatment should be continued for at least 14 days after
      cessation of fungemia. Susceptibility testing should be performed to identify
      resistance and to facilitate transition to oral treatment. (4) In persistent
      candidemia, echocardiography is an important investigation; ophthalmoscopy should
      be considered. CONCLUSION: Further efforts should be undertaken to increase the
      adherence to the essentials in the management of Candia bloodstream infection.

PMID- 30218312
TI  - Iodine Nutrition During Pregnancy: Past, Present, and Future.
AB  - Iodine is a trace element that is important for the synthesis of thyroid
      hormones. During pregnancy, iodine requirements are increased by approximately
      50% because of physiological changes. Adequate iodine status in pregnancy is
      crucial for maternal health and fetal growth. The World Health Organization (WHO)
      recommends a daily intake of 250 MUg iodine for pregnant women to maintain
      adequate iodine status. Severe iodine deficiency during pregnancy can result in a
      series of detrimental effects on maternal and fetal health including
      hypothyroidism, goiter, stillbirth, abortion, increased neonatal mortality,
      neurological damage, and intellectual impairment. Correction of severe iodine
      deficiency can reduce the risk of adverse impacts. However, the influences of
      mild-to-moderate maternal iodine deficiency on fetal neural development and
      cognitive function are less clear. The safety and efficacy of iodine
      supplementation in mildly-to-moderately iodine-deficient women also remain
      uncertain. In addition, excess iodine during pregnancy carries a risk of adverse
      effects, and the recommended safe upper limits of iodine intake are
      controversial. Effective iodine supplementation should be implemented, and
      routine monitoring is necessary to guarantee adequate iodine status.

PMID- 30218313
TI  - Hemodialysis Water Parameters as Predisposing Factors for Anemia in Patients in
      Dialytic Treatment: Application of Mixed Regression Models.
AB  - Contamination by metals and microbiological agents in hemodialysis water can
      cause clinical intercurrences in hemodialysis patients. Evaluating and assuring
      minimum levels of contamination from metals and microorganisms in hemodialysis
      water can improve patient safety. The objective of this study was to assess
      hemodialysis water quality in a major tertiary hospital in Brazil and investigate
      the relationship between hemodialysis water quality and clinical intercurrences
      in hemodialysis patients. A prospective-observational cohort study for evaluation
      of water quality parameters and clinical intercurrences present by patients (n =
      52) were performed from May 2014 to April 2015. Mixed linear regression models
      and binary regression models were fitted for water quality parameters and
      patients' clinical parameters. The increase in the levels of copper and nitrate
      in hemodialysis water was significant (p < 0.05) to explain anemia. Bone pain was
      related to age, sex (female), and hemodialysis treatment duration (years).
      Hypotensive episodes were related to serum sodium decrease. Aluminum in
      hemodialysis water was present in an average concentration higher than the
      permitted threshold (15.35 +/- 14.53 MUg/L). Cadmium, total coliforms,
      Escherichia coli, and endotoxins in hemodialysis water were not detected and the
      heterotrophic bacteria count was below the reference limit. These parameters'
      concentrations varied during the study, evidencing the need for continuous
      monitoring.

PMID- 30218314
TI  - The host age related occurrence of Alaria alata in wild canids in Latvia.
AB  - The trematode Alaria alata has a complex life cycle in which carnivore mammals
      may become infected by feeding on mesocercariae-infected, second intermediate
      hosts or paratenic hosts. Afterwards, young flukes migrate through various organs
      of the definitive host, including the diaphragm and the lungs, before reaching
      the small intestine. The aim of the present study was to establish the prevalence
      and infection intensity of A. alata in carnivore mammals, the host age and
      related occurrence of different A. alata development stages in particular animals
      in Latvia. Overall, samples from 992 animals (539 red foxes, 411 raccoon dogs and
      42 grey wolves) were examined using sedimentation and counting techniques to
      observe the presence of A. alata metacercariae and adult trematodes in each
      particular host. The present study, based on data collected over five hunting
      seasons (2010/2011-2014/2015), is a comprehensive study on the circulation of A.
      alata in wild canids in Latvia. A. alata was present in all species examined and
      the overall prevalence reached 86.2%. A significant positive correlation was
      observed between the burden of A. alata metacercariae and adult trematodes in
      raccoon dogs (rs = 0.27, p = 0.001) and red foxes (rs = 0.17, p = 0.0002). A
      significantly higher (p = 0.003) A. alata metacercariae mean intensity was
      observed in juvenile raccoon dogs compared to the one observed in adult raccoon
      dogs and red foxes from both age groups. The presence of both A. alata
      development stages in a particular animal concurrently and at different intensity
      levels may indicate primary infection and re-cured infection of the host.

PMID- 30218315
TI  - Correction to: A rare presentation of skull-base osteomyelitis with neurovascular
      sheath extension following external otitis resolved by PET/MRI.
AB  - The figure in the original published version of this article was omitted.

PMID- 30218316
TI  - EANM practical guidance on uncertainty analysis for molecular radiotherapy
      absorbed dose calculations.
AB  - A framework is proposed for modelling the uncertainty in the measurement
      processes constituting the dosimetry chain that are involved in internal absorbed
      dose calculations. The starting point is the basic model for absorbed dose in a
      site of interest as the product of the cumulated activity and a dose factor. In
      turn, the cumulated activity is given by the area under a time-activity curve
      derived from a time sequence of activity values. Each activity value is obtained
      in terms of a count rate, a calibration factor and a recovery coefficient (a
      correction for partial volume effects). The method to determine the recovery
      coefficient and the dose factor, both of which are dependent on the size of the
      volume of interest (VOI), are described. Consideration is given to propagating
      estimates of the quantities concerned and their associated uncertainties through
      the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and
      its associated uncertainty. This approach is demonstrated in a clinical example.

PMID- 30218317
TI  - Why harmonization is needed when using FDG PET/CT as a prognosticator:
      demonstration with EARL-compliant SUV as an independent prognostic factor in lung
      cancer.
AB  - BACKGROUND: To determine EARL-compliant prognostic SUV thresholds in a mature
      cohort of patients with locally advanced NSCLC, and to demonstrate how
      detrimental it is to use a threshold determined on an older-generation PET system
      with a newer PET/CT machine, and vice versa, or to use such a threshold with non
      harmonized multicentre pooled data. MATERIALS AND METHODS: This was a single
      centre retrospective study including 139 consecutive stage IIIA-IIIB patients.
      PET data were acquired as per the EANM guidelines and reconstructed with
      unfiltered point spread function (PSF) reconstruction. Subsequently, a 6.3 mm
      Gaussian filter was applied using the EQ.PET (Siemens Healthineers) methodology
      to meet the EANM/EARL harmonizing standards (PSFEARL). A multicentre study
      including non-EARL-compliant systems was simulated by randomly creating four
      groups of patients whose images were reconstructed with unfiltered PSF and PSF
      with Gaussian post-filtering of 3, 5, and 10 mm. Identification of optimal SUV
      thresholds was based on a two-fold cross-validation process that partitioned the
      overall sample into learning and validation subsamples. Proportional Cox hazards
      models were used to estimate age-adjusted and multivariable-adjusted hazard
      ratios (HRs) and their 95% confidence intervals. Kaplan-Meier curves were
      compared using the log rank test. RESULTS: Median follow-up was 28 months (1-104
      months). For the whole population, the estimated overall survival rate at 36
      months was 0.39 [0.31-0.47]. The optimal SUVmax cutoff value was 25.43 (95% CI:
      23.41-26.31) and 8.47 (95% CI: 7.23-9.31) for the PSF and for the EARL-compliant
      dataset respectively. These SUVmax cutoff values were both significantly and
      independently associated with lung cancer mortality; HRs were 1.73 (1.05-2.84)
      and 1.92 (1.16-3.19) for the PSF and the EARL-compliant dataset respectively.
      When (i) applying the optimal PSF SUVmax cutoff on an EARL-compliant dataset and
      the optimal EARL SUVmax cutoff on a PSF dataset or (ii) applying the optimal EARL
      compliant SUVmax cutoff to a simulated multicentre dataset, the tumour SUVmax was
      no longer significantly associated with lung cancer mortality. CONCLUSION: The
      present study provides the PET community with an EARL-compliant SUVmax as an
      independent prognosticator for advanced NSCLC that should be confirmed in a
      larger cohort, ideally at other EARL accredited centres, and highlights the need
      to harmonize PET quantitative metrics when using them for risk stratification of
      patients.

PMID- 30218318
TI  - Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective
      Measures and Self-reports of Non-adherence in ASPIRE.
AB  - This analysis compares self-reports of product use with objective measures of non
      adherence-quarterly plasma dapivirine levels and monthly residual dapivirine
      (DPV) levels in used rings-in MTN-020/ASPIRE, a phase 3 trial of a monthly DPV
      vaginal ring among women aged 18-45 years in Malawi, South Africa, Uganda and
      Zimbabwe. For participants on active product (N = 1211) we assessed self-reported
      monthly non-adherence, as measured by (1) whether the ring was ever out, and out
      for >= 12 h in the previous month and, (2) by a self-rating scale assessing
      ability to keep the vaginal ring inserted, and compared the self-reports to two
      biomarkers of non-use separately and as a composite measure. For this analysis, a
      plasma DPV value <= 95 pg/ml and residual ring >= 23.5 mg were used to classify
      non-adherence (i.e. the ring never being in the vagina the previous month).
      Compared to self-reports, non-adherence was found to be substantially higher for
      the composite measure as well as its two components, an indication that ring
      removal was likely underreported in the trial. The discrepancy between the self
      report measure of ring outage and the composite indicator was greater for those
      aged 18-21 than for those older, evidence that younger women are more likely to
      underreport non-adherence. Despite underreporting of non-adherence, self-reports
      of the ring never being out were significant in predicting the composite
      objective measure. Furthermore, the association between the self-rating scale and
      the objective measure was in the expected direction and significant, although 11%
      of those 18-21 and 7% of those 22+ who rated their ability to keep the ring
      inserted as good, very good or excellent in the 4 weeks prior to exit were
      considered non-adherent according to the objective measure. This analysis
      indicates that while self-reports are significantly associated with objective
      measures of adherence in the ASPIRE trial, they were inflated-more so by those
      younger-and therefore may have limited utility identifying those who have
      challenges using products as directed. ClinicalTrials.gov number NCT01617096.

PMID- 30218319
TI  - Couple Interdependence Impacts Alcohol Use and Adherence to Antiretroviral
      Therapy in Malawi.
AB  - In sub-Saharan Africa, harmful alcohol use among male drinkers is high and has
      deleterious consequences on adherence to antiretroviral therapy (ART), HIV
      clinical outcomes, and couple relationship dynamics. We conducted in-depth
      qualitative interviews with 25 Malawian couples on ART to understand how
      relationships influence adherence to ART, in which alcohol use emerged as a major
      theme. Almost half of men (40%) reported current or past alcohol use. Although
      alcohol use was linked to men's non-adherence, women buffered this harm by
      encouraging husbands to reduce alcohol use and by offering adherence support when
      men were drinking. Men's drinking interfered with being an effective treatment
      guardian for wives on ART and also weakened couple support systems needed for
      adherence. Relationship challenges including food insecurity, intimate partner
      violence, and extramarital relationships appeared to exacerbate the negative
      consequences of alcohol use on ART adherence. In this setting, alcohol may be
      best understood as a couple-level issue. Alcohol interventions for people living
      with HIV should consider approaches that jointly engage both partners.

PMID- 30218320
TI  - TanshinoneIIA Alleviates Inflammatory Response and Directs Macrophage
      Polarization in Lipopolysaccharide-Stimulated RAW264.7 Cells.
AB  - TanshinoneIIA (TanIIA) has been demonstrated to possess numerous biological
      effects. However, the specific effect of TanIIA on macrophage polarization has
      not been reported. In this study, it was revealed that TanIIA might play a
      pivotal role in macrophage polarization. As our results indicated, cell
      morphology was changed in RAW264.7 cells which were treated with LPS or
      LPS/TanIIA (0.1 MUM, 1 MUM, 10 MUM). Subsequently, pro-inflammatory cytokine TNF
      alpha and anti-inflammatory cytokine IL-10 were measured by ELISA kits.
      Furthermore, TanIIA enhanced the expression of M2 macrophage markers (Arg1 and
      FIZZ1) and decreased the expression of markers associated with M1 macrophage
      polarization (iNOS and IL-1beta). Increased expression of CD206 was also detected
      by flow cytometry in TanIIA-treated groups. Mechanistically, it was revealed that
      TanIIA modulated macrophage polarization by ameliorating mitochondrial function
      and regulating TLR4-HMGB1/CEBP-beta pathway. In addition, increased expression of
      miR-155 was observed in RAW264.7 cells incubated with LPS and were effectively
      inhibited by TanIIA. Taken together, it was suggested that TanIIA inhibits
      inflammatory response and promotes macrophage polarization toward an M2
      phenotype, which provides new evidence for the anti-inflammation activity of
      TanIIA.

PMID- 30218321
TI  - Ability of Platelet-Derived Extracellular Vesicles to Promote Neutrophil
      Endothelial Cell Interactions.
AB  - We tested the ability of platelet-derived extracellular vesicles (PEV) to promote
      adhesion of flowing neutrophils to endothelial cells (EC). PEV were collected
      from platelets stimulated with collagen-related peptide, and differential
      centrifugation was used to collect larger vesicles enriched for platelet membrane
      microvesicles (PMV) or smaller vesicles enriched for platelet exosomes (Pexo).
      Vesicle binding and resultant activation of neutrophils and EC were assessed by
      flow cytometry. Flow-based adhesion assays assessed binding of neutrophils
      directly to deposited vesicles or to EC, after neutrophils or EC had been treated
      with vesicles. PEV bound efficiently to neutrophils or EC, with resultant
      upregulation of activation markers. Binding was Ca++-dependent and dominantly
      mediated by CD62P for neutrophils or by integrins for EC. Deposited PEV supported
      mainly transient attachments of flowing neutrophils through CD62P and some stable
      adhesion through CXC-chemokines. Neutrophil adhesion to EC was promoted when
      either cell was pre-treated with PEV, although the effect was less prominent when
      EC were pre-activated with tumor necrosis factor-alpha. The pro-adhesive effects
      on neutrophils could largely be attributed to the larger PMV rather than Pexo.
      Thus, surface-bound PEV can capture flowing neutrophils, while PEV also activate
      neutrophils and EC to promote interactions. PEV may potentiate inflammatory
      responses after tissue injury.

PMID- 30218322
TI  - Preprints: Facilitating early discovery, access, and feedback.

PMID- 30218323
TI  - Passion projects and disorienting dilemmas.

PMID- 30218324
TI  - Agrobacterium-mediated transformation of the ascomycete mushroom Morchella
      importuna using polyubiquitin and glyceraldehyde-3-phosphate dehydrogenase
      promoter-based binary vectors.
AB  - Morchella importuna is a worldwide distributed edible mushroom with high
      ecological and economic values, but the molecular and genetic research about this
      mushroom has been hindered due to lack of an efficient transformation method.
      Here, we report for the first time the successful transformation of M. importuna
      by using a hypervirulent Agrobacterium tumefaciens strain bearing the constructed
      binary plasmid p1391-U-GUS. The selectable markers used were the genes for
      hygromycin resistance under the control of the polyubquitin promoter from M.
      importuna. The reporter genes were those for enhanced green fluorescent protein
      (EGFP) and the beta-Glucuronidase (GUS) under the control of glyceraldehyde-3
      phosphate dehydrogenase promoter and polyubquitin promoter respectively. The
      presence of the reporter gene EGFP in the transformants was confirmed by the
      fluorescence and confocal microscope and molecular analysis and that of the
      reporter gene GUS was verified by enzyme activity and molecular analysis. The
      analysis results of both reporter genes indicated that Agrobacterium-mediated
      transformation was successfully performed in M. importuna.

PMID- 30218325
TI  - Tasty rewards for ants: differences in elaiosome and seed metabolite profiles are
      consistent across species and reflect taxonomic relatedness.
AB  - Diaspores of myrmecochorous plants consist of a seed (or fruit) and an attached
      appendage (elaiosome) which attracts ants. The elaiosome is a food resource for
      ants, whereas the seed is an energy source for subsequent germination and plant
      establishment. Although myrmecochory occurs in many phylogenetically unrelated
      lineages, multiple phylogenetic lineages display similar variation in elaiosome
      and seed metabolite composition due to convergent evolution. We focused on four
      families (Amaryllidaceae, Boraginaceae, Papaveraceae and Poaceae) each
      represented by two species from different genera. Diaspores of three populations
      per species were sampled and concentrations of 60 metabolites from five groups
      (amino acids, fatty acids, organic acids, polyols and sugars) were determined for
      both elaiosomes and seeds. Variability in metabolite composition was decomposed
      by hierarchical ANOVA and variation partitioning using redundancy analysis
      (reflecting both species nested within families, crossed with seed vs.
      elaiosome). Differences in the metabolite composition of elaiosomes and seeds
      were consistent across multiple phylogenetic origins (with more pronounced
      differences at the level of individual metabolites than at the level of
      metabolite groups) and supported the idea of convergent evolution under strong
      selection pressure. Elaiosomes contained higher amounts of easily digestible
      metabolites (especially amino acids) than seeds. Fatty acids were not more
      concentrated in elaiosomes, which contradicts the literal translation of
      "elaiosome" (= oil body). The differentiation of metabolite composition closely
      reflected taxonomic relatedness, particularly at the family level. Differences
      among populations within species were small, so the metabolite composition can
      thus be considered as a trait with relatively low intraspecific variability.

PMID- 30218326
TI  - Incorporation of Collagen from Marine Sponges (Spongin) into Hydroxyapatite
      Samples: Characterization and In Vitro Biological Evaluation.
AB  - Biomaterial-based bone grafts have an important role in the field of bone tissue
      engineering. One of the most promising classes of biomaterials is collagen,
      including the ones from marine biodiversity (in general, called spongin (SPG)).
      Also, hydroxyapatite (HA) has an important role in stimulating bone metabolism.
      Therefore, this work investigated the association of HA and SPG composites in
      order to evaluate their physico-chemical and morphological characteristics and
      their in vitro biological performance. For this, pre-set composite disks were
      evaluated by means of mass loss after incubation, pH, Fourier transform infrared
      spectroscopy (FTIR), scanning electron microscopy (SEM), and "in vitro" cell
      viability. pH measurements showed no statistical difference between groups.
      Moreover, a higher mass loss was observed for HA/SPG70/30 compared to the other
      groups for all experimental periods. Moreover, SEM representative micrographs
      showed the degradation of the samples with and without immersion. FTIR analysis
      demonstrated the absorption peaks for poly(methyl methacrylate) (PMMA), HA, and
      SPG. A higher L292 cell viability for control and PMMA was observed compared to
      HA and HA/SPG 90/10. Also, HA/SPG 70/30 showed higher cell viability compared to
      HA and HA/SPG 90/10 on days 3 and 7 days of culture. Furthermore, HA showed a
      significant lower MC3T3 cell viability compared to control and HA/SPG 70/30 on
      day 3 and no significant difference was observed between the composites in the
      last experimental period. Based on our investigations, it can be concluded that
      the mentioned composites were successfully obtained, presenting improved
      biological properties, especially the one mimicking the composition of bone (with
      70% of HA and 30% of SPG). Consequently, these data highlight the potential of
      the introduction of SPG into HA to improve the performance of the graft for bone
      regeneration applications. Further long-term studies should be carried out to
      provide additional information concerning the late stages of material degradation
      and bone healing in the presence of HA/SPG.

PMID- 30218327
TI  - Intracellular Metabolic Changes of Rhodococcus sp. LH During the Biodegradation
      of Diesel Oil.
AB  - In recent years, some marine microbes have been used to degrade diesel oil.
      However, the exact mechanisms underlying the biodegradation are still poorly
      understood. In this study, a hypothermophilous marine strain, which can degrade
      diesel oil in cold seawater was isolated from Antarctic floe-ice and identified
      and named as Rhodococcus sp. LH. To clarify the biodegradation mechanisms, a gas
      chromatography-mass spectrometry (GC-MS)-based metabolomics strategy was
      performed to determine the diesel biodegradation process-associated intracellular
      biochemical changes in Rhodococcus sp. LH cells. With the aid of partial least
      squares-discriminant analysis (PLS-DA), 17 differential metabolites with variable
      importance in the projection (VIP) value greater than 1 were identified. Results
      indicated that the biodegradation of diesel oil by Rhodococcus sp. LH was
      affected by many different factors. Rhodococcus sp. LH could degrade diesel oil
      through terminal or sub-terminal oxidation reactions, and might also possess the
      ability to degrade aromatic hydrocarbons. In addition, some surfactants,
      especially fatty acids, which were secreted by Rhodococcus into medium could also
      assist the strain in dispersing and absorbing diesel oil. Lack of nitrogen in the
      seawater would lead to nitrogen starvation, thereby restraining the amino acid
      circulation in Rhodococcus sp. LH. Moreover, nitrogen starvation could also
      promote the conversation of relative excess carbon source to storage materials,
      such as 1-monolinoleoylglycerol. These results would provide a comprehensive
      understanding about the complex mechanisms of diesel oil biodegradation by
      Rhodococcus sp. LH at the systematic level.

PMID- 30218328
TI  - Improvement of ternary fuel combustion with various injection pressure strategies
      in a toroidal re-entrant combustion chamber.
AB  - The present experimental work focuses on the influence injection pressure and
      toroidal re-entrant combustion chamber in a single cylinder diesel engine fuelled
      with ternary fuel (diesel-biodiesel-ethanol) blend. Ternary fuel (TF) is prepared
      by blending 70% diesel, 20% biodiesel, and 10% ethanol blends and its fuel
      properties were investigated and compared with diesel fuel. Since the physic
      chemical properties of TF are well behind the diesel fuel, it is proposed to be
      blended with 20 ppm alumina nano additives which act as an ignition enhancer and
      catalytic oxidizer. The resulting fuel mixture (TF + 20 ppm alumina additive) is
      named as high performance fuel (HPF). Experimentations were conducted on HPF
      subjected to various injection pressures of 18 MPa, 20 MPa, 22 MPa, and 24 MPa
      respectively and are operated in toroidal re-entrant chamber geometry (TG) at an
      injection timing of 22 obTDC. From experimentation, it was identified that, for
      TG-HPF, higher injection pressure of 22 MPa ensued highest BTE (Brake Thermal
      Efficiency) of 35.5% and lowest BSEC (Brake Specific Fuel Consumption) of 10.13
      MJ/kWh owing to the pooled effect of higher swirl formation, improved atomization
      enhanced evaporation rate, and better air-fuel mixing. Emission wise TG-HPF
      operated at 22 MPa lowered the HC (hydrocarbon), CO (carbon monoxide), and smoke
      emissions by 18.88%, 7.19%, and 5.02%, but with marginally improved NOx (oxides
      of nitrogen) and CO2 (carbon dioxide) emissions by 3.92% and 3.89% respectively.
      In combustion point of view, it is observed that injection pressure increased the
      cylinder pressure, heat release rate (HRR), and cumulative heat release rate
      (CHRR) by 5.35%, 5.08%, and 3.38% respectively indicating improved combustion
      rate as a result of enhanced atomization, evaporation, and high turbulence
      inducement. Overall, it is concluded that operating the ternary fuel at 22 MPa
      injection pressure at toroidal re-entrant combustion chamber results in improved
      performance and minimized emissions.

PMID- 30218329
TI  - Cobalt and nickel content in Hydrocharis morsus-ranae and their bioremoval from
      single- and binary solutions.
AB  - Aquatic macrophytes are known to remove trace metals from surrounding water. In
      the present study, an attempt was made to evaluate the phytofiltration capacity
      of Hydrocharis morsus-ranae and to show competition between cobalt (Co) and
      nickel (Ni) for the better understanding of metal bioaccumulation in the species.
      In a laboratory experiment, H. morsus-ranae was exposed to separate (single) and
      binary solutions of these metals: Ni 10.7, 18.7, 32.7, 57.1, and 100 (MUg L-1);
      Co 5.33, 9.32, 16.3, 28.6, and 50.0 (MUg L-1); and 10.7 Ni + 5.33 Co, 18.7 Ni +
      9.32 Co, 32.7 Ni + 16.3 Co, 57.1 Ni + 28.6 Co, 100 Ni + 50.0 Co (MUg L-1). The
      content of Co and Ni in the plant increased with the increasing concentration in
      the growth medium. Competition between the metals was seen during uptake in
      binary solutions. Ni interfered with the accumulation of Co, resulting in a lower
      Co content than in plants cultivated in Co solutions. A particularly high Co
      content (up to 155 mg kg-1 dry weight [d.w.]) and high efficiency of Ni uptake
      (Bioaccumulation Factor (BF) 2572-7239) makes the species a very good accumulator
      of these metals. The high content of both trace metals in plant tissues (up to
      511 mg kg-1 d.w. Ni and 155 mg kg-1 d.w. Co) did not affect its growth,
      indicating tolerance of these toxicants. The plant showed excellent ability in
      removing Co (up to 98.6% in solution with 5.33 MUg L-1 Co) and Ni (up to 91.4% in
      solution with 57.1 MUg L-1 Ni and 28.6 MUg L-1 Co) from nutrient solution. The
      results suggest that H. morsus-ranae may be useful for the phytoremediation of
      water bodies contaminated with Co and Ni.

PMID- 30218330
TI  - Germanium in the soil-plant system-a review.
AB  - Germanium (Ge) is widespread in the Earth's crust. As a cognate element to
      silicon (Si), Ge shows very similar chemical characteristics. Recent use of Ge/Si
      to trace Si cycles and changes in weathering over time, growing demand for Ge as
      raw material, and consequently an increasing interest in Ge phytomining have
      contributed to a growing interest in this previously rather scarcely considered
      element in geochemical studies. This review deals with the distribution of Ge in
      primary minerals and surface soils as well as the factors influencing the
      mobility of Ge in soils including the sequestration of Ge in secondary mineral
      phases and soil organic matter. Furthermore, the uptake and accumulation of Ge in
      plants and effects of plant-soil relationships on the availability of Ge in soils
      and the biogeochemical cycling of Ge are discussed. The formation of secondary
      soil minerals and soil organic matter are of particular importance for the
      concentration of Ge in plant-available forms. The transfer from soil to plant is
      usually low and shows clear differences between species belonging to the
      functional groups of grasses and forbs. Possible uptake mechanisms in the
      rhizosphere are discussed. However, the processes that are involved in the
      formation of plant-available Ge pools in soils and consequently its
      biogeochemical cycling are not yet well understood. There is, therefore, a need
      for future studies on the uptake mechanisms and stoichiometry of Ge uptake under
      field conditions and plant-soil-microbe interactions in the rhizosphere as well
      as the chemical speciation in different plant parts.

PMID- 30218331
TI  - Metal wet deposition in the Three Gorges Reservoir (TGR) region of Southwest
      China.
AB  - Metal wet deposition has become an environmental concern because of its threats
      to soil or water quality and human health. This study was to collect rainfall
      waters in 2016 from seven sites, representing urban, town, rural, and wetland,
      within the Three Gorges Reservoir (TGR) region of Southwest China, determine the
      metal concentration and flux (Zn, Mn, Cu, As, Cd, Pb), and identify their
      possible sources. Results indicated that Zn was the most abundant metal with a
      concentration of 16.92 MUg L-1 in fall and 19.91 MUg L-1 in winter and flux of
      4.71 mg m-2 in fall, while Cd was the least with a monthly mean concentration of
      0.02-0.37 MUg L-1. Among the seven sites, urban (FL) had the highest values of
      both concentrations of metals (Zn, Cu, Pb) and fluxes of metals (Mn, As), which
      significantly differed from the other sites. Component and redundancy analysis
      suggested that fossil fuel and biomass combustion be a potential metal source.
      Enrichment factors, box model, and potential ecological risk index showed that
      the TGR water quality could face a high risk due to wet metal deposition,
      especially Cd. Data could provide a valuable aid in mitigating metal pollution,
      developing the best watershed management practices, as well as safeguarding water
      quality and human health in the TGR region or other reservoir regions.

PMID- 30218332
TI  - Testing EKC hypothesis with energy and sustainable development challenges: a
      fresh evidence from belt and road initiative economies.
AB  - Diverse impact of greenhouse gasses (GHGs) over the landscape of environment is
      generally believed in literature. As CO2 emission acutely leads to GHGs is a
      major contributor for global warming, it creates a serious pressure on natural
      resources and ecological settings. Similarly, low-carbon (CO2) economy, plenty of
      energy resources, and sustainable growth are a big ask for worldwide economies in
      this era of mechanization. This paper analyzes the Environmental Kuznets Curve
      (EKC) hypothesis, for Belt and Road Initiative (BRI) economies, to contend the
      role of mega projects in BRI as an attribute for ecological detriments. The on
      hand study engages fresh data information ranging from 1981 to 2016 holding with
      heterogeneity and cross-sectional dependence as a special deliberation. The
      calculated outcomes expose that, mean group estimator provides strong evidence
      and favor the existence of EKC approximately in every region. The long-run
      influence is measured by pooled mean group estimators, which shows significant
      outcomes in every region; additionally, the EKC hypothesis affirmed in the long
      run especially for developed economies. Mega projects, i.e., BRI requisite
      immense energy sources to accomplishing the enclosed projects efficiently and
      effectively. The positive association between carbon emission and energy
      consumption troubled the governments to make policies for restraining the
      magnitude of carbon emission and controls energy usage for enduring environment
      to its original position. Next, the valuations depicted the dense recommendations
      for state administrations in capacity of rigorous level supremacy, trash managing
      campaigns, renewable energy reliance, and advance for desirable judgments to
      sterilize the atmosphere.

PMID- 30218333
TI  - Resistance of alfalfa and Indian mustard to Cd and the correlation of plant Cd
      uptake and soil Cd form.
AB  - Phytoremediation of heavy metal-contaminated soil is considered to be one
      ecological environmental protection way that is effective and economical. The
      selection of suitable hyperaccumulators is a key issue for phytoremediation of
      heavy metal-contaminated soil. Pot experiments were conducted to study the
      effects of different Cd levels (0, 75, 150, 300, and 600 mg kg-1 Cd) on the dry
      weight, antioxidant enzyme activities, malondialdehyde (MDA) contents, Cd
      concentration, Cd accumulation, and soil Cd form distribution ratio (FDC) of
      alfalfa (Medicago sativa L.) and Indian mustard (Brassica juncea L.). The
      correlations between Cd concentration in shoots and roots of alfalfa and Indian
      mustard and soil Cd form were also investigated. The results showed that with the
      increase of soil Cd levels, dry weight of shoot and root of alfalfa and Indian
      mustard significantly decreased, which decreased by 50.0-71.8% and 29.6-59.3%
      (alfalfa), 59.6-89.0% and 64.3-74.8% (India mustard), respectively, compared with
      the control. With the increase of soil Cd level, superoxide dismutase (SOD)
      activity in shoot of alfalfa significantly increased. Catalase (CAT) activity and
      malondialdehyde contents in shoots and roots of alfalfa and Indian mustard, as
      well as superoxide dismutase activity in the roots of alfalfa and Indian mustard
      increased first and then decreased with the increase of soil Cd level. With
      increasing Cd stress, Cd concentration in shoots and roots of alfalfa and Indian
      mustard significantly increased. At soil Cd level of 75 mg kg-1, Cd
      concentrations in shoots of alfalfa and Indian mustard exceeded the critical
      value of Cd-hyperaccumulator (100 mg kg-1), which was 356.46 mg kg-1 and 308.74
      mg kg-1, respectively. Cadmium concentrations in shoots and roots of plants were
      in the order of that of alfalfa > Indian mustard; total Cd accumulation in the
      aboveground tissues and roots of the plants was in the order of that of Indian
      mustard > alfalfa at the same Cd level. With increasing soil Cd level, Cd
      concentrations of exchangeable form (EXC-Cd), carbonate-bound form (CAB-Cd), iron
      manganese oxide-bound form (FeMn-Cd), organic-bound form (OM-Cd), and residual
      form (RES-Cd) showed an increasing trend. The form distribution ratio of soil Cd
      forms in alfalfa's rhizosphere was in the order of that of exchangeable form Cd >
      carbonate-bound form Cd > iron-manganese oxide-bound form Cd > residual form Cd >
      organic-bound form Cd. Except for organic-bound form Cd, soil Cd forms were
      significantly positively correlated with Cd concentration in shoot and root (P <
      0.01). Comprehensively considering the biomass and Cd accumulation, Indian
      mustard is more suitable as remediation material for soil Cd pollution.

PMID- 30218334
TI  - Future intensification of summer hypoxia in the tidal Garonne River (SW France)
      simulated by a coupled hydro sedimentary-biogeochemical model.
AB  - Projections for the next 50 years predict a widespread distribution of hypoxic
      zones in the open and coastal ocean due to environmental and global changes. The
      Tidal Garonne River (SW France) has already experienced few episodic hypoxic
      events. However, predicted future climate and demographic changes suggest that
      summer hypoxia could become more severe and even permanent near the city of
      Bordeaux in the next few decades. A 3D model, which couples hydrodynamic,
      sediment transport, and biogeochemical processes, is applied to assess the impact
      of factors submitted to global and regional climate changes on oxygenation in the
      turbidity maximum zone (TMZ) of the Tidal Garonne River during low-discharge
      periods. The model simulates an intensification of summer hypoxia with an
      increase in temperature, a decrease in river flow or an increase in the local
      population, but not with sea level rise, which has a negligible impact on
      dissolved oxygen. Different scenarios were tested by combining these different
      factors according to the regional projections for 2050 and 2100. All the
      simulations showed a trend toward a spatial and temporal extension of summer
      hypoxia that needs to be considered by local water authorities to impose
      management strategies to protect the ecosystem.

PMID- 30218335
TI  - Investigation of antibiotics in sea cucumbers: occurrence, pollution
      characteristics, and human risk assessment.
AB  - Occurrence and distribution of 24 antibiotics from 7 categories were screened in
      sea cucumbers (Echinodermata: Holothuroidea) collected from different coastal
      regions of China. The samples were simultaneously extracted and purified using
      accelerated solvent extraction with in-cell clean-up and analyzed by ultra
      performance liquid chromatography-tandem mass spectrometry. A total of ten
      antibiotics were detected in the sea cucumbers with concentrations ranging from
      not detected to 32.8 MUg/kg (dry weight). Sulfonamides are predominant
      antibiotics with a mean concentration of 11.5 MUg/kg (dry weight), followed by
      macrolides (11.3 MUg/kg, dry weight) and fluoroquinolones (11.2 MUg/kg, dry
      weight). High concentrations of the antibiotics were found in the samples from
      the South China Sea, implying that the antibiotic pollution in sea cucumbers was
      geographical region-dependent, which was further confirmed by principal component
      analysis. It was also found that the antibiotic levels are slightly higher in
      instant sea cucumbers than in the dried ones. Hazard quotient calculation
      suggested no obvious human health risks associated with the consumption of sea
      cucumbers regarding antibiotics.

PMID- 30218336
TI  - Treatment of 1,4-dioxane and trichloroethene co-contamination by an activated
      binary persulfate-peroxide oxidation process.
AB  - The efficacy of a binary oxidant system, hydrogen peroxide (H2O2) and persulfate,
      was investigated for treatment of 1,4-dioxane (dioxane) and trichloroethene (TCE)
      co-contamination. Batch experiments were conducted to examine the catalytic
      efficiency of Fe2+ and NaOH-based activation, oxidant decomposition rates,
      contaminant degradation effectiveness, and competitive degradation effects. For
      NaOH activation, the oxidant decomposition rate was moderate and sustained during
      the entire test period of 96 h. However, dioxane degradation was limited (~ 33%).
      Conversely, the oxidants were depleted within 24 h for the Fe2+-activated system,
      and dioxane degradation was complete within 4 h. The activation and radical
      generation processes were different between Fe2+ and NaOH activation. Both
      dioxane and TCE underwent complete degradation in the co-contaminant experiment.
      The results of this study indicate that the Fe2+-catalyzed binary hydrogen
      peroxide-persulfate oxidant system is effective for oxidation of the tested
      contaminants separately and as co-contaminants.

PMID- 30218337
TI  - Agricultural environmental total factor productivity in China under technological
      heterogeneity: characteristics and determinants.
AB  - With limited resources, growing environment constraints and downward pressure on
      the economy, increasing agricultural environmental total factor productivity
      (AETFP) and its contribution to agricultural growth is significant for
      transforming agricultural development to make it more resource efficient and
      environment-friendly. This paper considered technological heterogeneity in
      different regions of China and measured AETFP in 30 provinces from 1997 to 2015
      using the Metafrontier Malmquist-Luenberger (MML) productivity index. Multi
      dimensional analysis was made on temporal and spatial characteristics, evolution
      patterns, and influencing factors of AETFP in China. The results showed that: (1)
      AETFP increased in the Ninth, Tenth, Eleventh, and Twelfth Five-Year Plan
      periods, with average annual growth rates of 0.76%, 0.88%, 1.17%, and 0.87%,
      respectively. (2) The average annual growth rate of AETFP in the eastern,
      central, and western regions decreased successively. The eastern region generally
      had played a leading role. The central region had a catch-up effect on
      environmental production technologies from the eastern region, while the western
      region lacked the catch-up effect. (3) The dynamic evolution of AETFP had
      prominent features. For the whole nation, the kernel density curve of AETFP
      continuously moved to the right. The main peak value continuously decreased and
      the width of the main peak continuously increased. The internal differences of
      AETFP in the eastern and western regions exhibited an increasing trend, while the
      internal differences of AETFP in the central region showed little change. (4)
      There was an inverted U-shaped relationship between agricultural economic growth
      and AETFP. Both the disaster rate and planting structure had a negative impact on
      AETFP with varying degrees of significance. Income gaps between urban and rural
      areas can partially offset the role of urbanization in promoting the growth of
      AETFP. The greater the income differences between urban and rural areas, the
      weaker the role of urbanization in promoting the growth of AETFP. These findings
      can help the government determine policies to change the agricultural development
      mode and formulate effective measures to improve AETFP.

PMID- 30218338
TI  - Adsorption of ionic liquids onto an activated carbon: kinetic modeling studies.
AB  - In this study, the uptake of hydrophobic bromide-based ionic liquids (ILs)
      (imidazolium, pyrrolidinium, and pyridinium) from aqueous solutions onto
      granulated and fabric-based microporous activated carbons (ACs). Surface
      characterization study shows that both ACs have basic pHpzc, like 8.7 for
      granulated AC and 8.0 for fabric AC. Granulated AC have ten times higher phenolic
      groups 0.2 meq g-1 compared to fabric AC which is 0.03 meq g-1. The kinetics of
      adsorption was remarkably slower for ILs on granulated/fabric AC than milled one.
      We also studied the effect of AC size on the rate of adsorption in the operating
      conditions. In order to improve the adsorption kinetics of ILs with ACs,
      different phenomenological and empirical kinetic models like as pseudo-first
      order, Boyd model, pseudo-second-order diffusion model and Elovich were applied
      on the kinetic experimental data. The analysis of kinetic specified that the
      adsorption mechanism of ILs onto ACs is controlled mainly by the mass transfer
      through the pores of ACs. So, the selection of appropriate adsorbent particle
      size of AC plays a main role for the development of viable IL adsorption.
      Graphical abstract ?.

PMID- 30218339
TI  - Fabrication of manganese-based Zr-Fe polymeric pillared interlayered
      montmorillonite for low-temperature selective catalytic reduction of NOx by NH3
      in the metallurgical sintering flue gas.
AB  - A series of Zr-Fe (Zr/Fe = 4:0, 3:1, 2:2, 1:3, 0:4) polymeric pillared
      interlayered montmorillonite loading 10 wt.% MnOx (Mn/Zr-Fe-PILM) were
      investigated for the selective catalytic reduction of NOx by NH3 (NH3-SCR) in
      metallurgical sintering flue gas. The X-ray diffraction (XRD), N2 adsorption
      desorption isotherm, scanning electron microscope (SEM), and ammonia temperature
      programmed desorption (NH3-TPD) were used to analyze the physicochemical
      property. The Fe polymerized with Zr exchanged to montmorillonite can improve the
      Mn/Zr-Fe-PILM low-temperature NOx conversion and N2 selectivity. The Mn/Zr-Fe
      PILM (1:3) shows the highest NOx conversion between 140 and 180  degrees C. The
      XRD results suggest that the growth of crystalline ZrO2 phase is intensely
      restrained for the Fe2O3 migration into the ZrO2 lattice. The ZrO2 and MnOx have
      an excellent dispersion in montmorillonite. The N2 adsorption result illustrates
      that the increase of Fe molar content in the Zr-Fe-PILM support increases the
      catalyst-specific surface area. The NH3-TPD results elucidate that the Mn/Zr-Fe
      PILM (1:3) has the most total acid sites. Therefore, the low-temperature
      catalytic activity of the Mn/Zr-Fe-PILM (1:3) has been assigned to the large
      specific surface area, abundant acid sites, and the dispersion of metallic
      oxides.

PMID- 30218340
TI  - Organic matter facilitates the binding of Pb to iron oxides in a subtropical
      contaminated soil.
AB  - The bioavailability and potential uptake of heavy metals by crops is
      fundamentally influenced by the forms of metals in soils. Organic matter plays an
      important role in controlling the transformation of heavy metal fractionations in
      soils. However, long-term effects of organic matter on heavy metal speciation
      remains highly uncertain. In this study, rice straw was introduced to a
      subtropical Pb-contaminated soil for 2-year period so as to clarify the
      redistribution of Pb fractions and their correlations with soil properties. By
      combining sequential extraction and X-ray absorption fine structure spectroscopy,
      we find that lead is predominantly presented in Fe oxide-bound, surface adsorbed,
      and residual fractions in the soil. The incorporation of rice straw can
      effectively reduce the labile species of Pb by promoting the binding of Pb to
      iron oxides. Furthermore, aging leads to the transfer of considerable amounts of
      Pb to the association with Fe oxides and this transformation is enhanced by the
      presence of organic matter. Organic matter input and soil aging tend to shift Pb
      to amorphous Fe oxides than crystalline Fe oxides. The correlation analysis shows
      that Fe oxide fractions play vital roles in controlling the forms of Pb in soil.
      This study presents the first result regarding the long-term effect of organic
      matter on the redistribution of Pb in naturally polluted soil, which is useful
      for understanding the fate of Pb and developing remediation strategies for Pb
      polluted soils.

PMID- 30218341
TI  - Computational Models of Polymer Synthesis Driven by Dehydration/Rehydration
      Cycles: Repurination in Simulated Hydrothermal Fields.
AB  - Cycles of biologically relevant reactions are an alternative to an origin of life
      emerging from a steady state away from equilibrium. The cycles involve a rate at
      which polymers are synthesized and accumulate in microscopic compartments called
      protocells, and two rates in which monomers and polymers are chemically degraded
      by hydrolytic reactions. Recent experiments have demonstrated that polymers are
      synthesized from mononucleotides and accumulate during cycles of hydration and
      dehydration, which means that the rate of polymer synthesis during the dehydrated
      phase of the cycle is balanced (but not dominated) by the rate of polymer
      hydrolysis during the hydrated phase of the cycle. Furthermore, depurination must
      be balanced by the reverse process of repurination. Here we describe a
      computational model that was inspired by experimental results, can be generalized
      to accommodate other reaction parameters, and has qualitative predictive power.

PMID- 30218342
TI  - Hepatocellular Carcinoma in Transplantable Child-Pugh A Cirrhotics: Should Cost
      Affect Resection vs Transplantation?
AB  - BACKGROUND: There is no consensus regarding the optimal surgical treatment for
      transplantable hepatocellular carcinoma (HCC) patients with well-compensated
      cirrhosis. Our aim was to compare outcomes between Child-Pugh A (CPA) cirrhotics
      who underwent liver resection or transplantation for HCC. METHODS:
      Clinicopathologic data were retrospectively collected for all surgically treated
      HCC patients between 7/1992 and 12/2015. Disease-free survival (DFS) and overall
      survival (OS) were calculated from the time of operation or diagnosis (intention
      to-treat analysis including patients removed from the transplant list). The
      average overall cost including pre-operative and post-operative procedures was
      calculated for each group. RESULTS: Of the 513 surgically treated HCC patients,
      184 had CPA cirrhosis and fulfilled the Milan criteria (MC). Of those, 95 (52%)
      were resected and 89 (48%) were transplanted. Twenty-two patients were removed
      from the transplant list. Transplanted patients were younger (p < 0.001), had a
      higher MELD score (p < 0.001) and a higher frequency of hepatitis C (p < 0.001).
      Length of stay and postoperative complication rates were similar between groups.
      DFS was longer for transplanted patients (3-, 5-, and 10-year DFS rates 48, 44,
      31% vs 96, 94, 94%, respectively, p < 0.001). OS was similar between groups (3-,
      5-, and 10-year OS rates 76, 62, 41% vs 82, 77, 53%, respectively, p = 0.07).
      Only size of greatest lesion and T stage were independent predictors of OS. The
      cost was much higher for the transplant group, even when accounting for the
      treatment of recurrences ($37,391 vs $137,996). CONCLUSIONS: Since OS is similar
      between CPA cirrhotics within the MC undergoing resection or transplantation for
      HCC, but cost is significantly higher for transplantation. Resection should be
      considered for first-line treatment.

PMID- 30218343
TI  - [Ultrasound diagnostics for myotendinous injuries and insertion tendinopathies of
      the elbow joint].
AB  - INTRODUCTION: Acute capsular injuries of the elbow joint and its ligaments
      predominantly occur after joint dislocation or subluxation. Together with lateral
      and medial epicondylitis they represent a common injury pattern in radiology,
      orthopedic and trauma surgery. CLINICAL ISSUE: Because of the complexity of the
      elbow joint, knowledge of the elbow dislocation and injury pattern as well as the
      anatomy is essential in order to adequately estimate the injury severity and
      joint stability. This is crucial for the correct diagnosis and choice of
      treatment. Systematic physical examination and careful radiographic evaluation
      are components of an adequate management of acute soft tissue elbow injuries.
      DIAGNOSTIC WORK-UP: The cost-effective ultrasound has emerged as a useful imaging
      modality for the diagnosis of acute joint and soft tissue pathologies especially
      in the acute phase after injury. Ultrasound as a diagnostic tool enables
      visualization of motion sequences during dynamic examination and therefore a
      better understanding of pathologies. Ultrasound examinations of the most common
      injuries of the elbow joint are presented in this overview.

PMID- 30218344
TI  - Parental Knowledge Discrepancies: Examining the Roles of Warmth and Self
      Disclosure.
AB  - Discrepancies between parents' and adolescents' reports in parental knowledge of
      adolescents' daily activities and whereabouts are common and have implications
      for adolescents' well-being and school success. Grounded in a family systems
      perspective utilizing reports from parents and adolescents, the goal of this
      study was to explore the extent to which parent-adolescent warmth and adolescent
      self-disclosure could account for discrepancies in parental knowledge by testing
      the indirect effects linking warmth to discrepancies in parental knowledge via
      adolescent self-disclosure. Participants were early adolescents (N = 172; 53%
      female) and their parents (90% mothers). Adolescents (57% African American/Black,
      18% multiracial, 17% White/Caucasian, 7% Hispanic/Latino and 1% Asian American)
      attended a Midwestern, Title 1, urban, public middle school. Using structural
      equation modeling, findings showed that parent-adolescent warmth significantly
      predicted adolescent self-disclosure, which in turn predicted fewer discrepancies
      in parental knowledge. The findings from this study help in understanding the
      factors that contribute to parental knowledge discrepancies and highlight
      potential targets for family interventions.

PMID- 30218345
TI  - An Update of Efficacy and Safety of Cetuximab in Metastatic Colorectal Cancer: A
      Narrative Review.
AB  - Colorectal cancer is the second most common cancer, representing 13% of all
      diagnosed cancers. Cetuximab is a recombinant chimeric monoclonal IgG1 antibody
      and epidermal growth factor receptor (EGFR) inhibitor. Cetuximab is approved for
      the first-line treatment in combination with chemotherapy or as a single agent in
      patients who have failed or are intolerant to chemotherapy in patients with EGFR
      expressing, RAS wild-type metastatic colorectal cancer. Cetuximab efficacy
      emerged from studies that were conducted to approve the drug. Cetuximab is well
      tolerated; its toxicities are caused by its mechanism of action and the most
      common adverse reaction is skin toxicity. The main purpose of this manuscript is
      to present an update on the evidence-based summary of efficacy and safety and on
      the cost-effectiveness of cetuximab. Furthermore, it suggests a management of
      adverse drug reactions to improve the tolerability of the drug.

PMID- 30218346
TI  - Functional analysis of a homologue of the FLORICAULA/LEAFY gene in litchi (Litchi
      chinensis Sonn.) revealing its significance in early flowering process.
AB  - Litchi (Litchi chinensis Sonn.) is an important subtropical fruit crop with high
      commercial value due to its high nutritional values and favorable tastes.
      However, irregular bearing attributed to unstable flowering is a major ongoing
      problem for litchi producers. Previous studies indicate that low-temperature is a
      key factor in litchi floral induction. In order to reveal the genetic and
      molecular mechanisms underlying the reproductive process in litchi, we had
      analyzed the transcriptome of buds before and after low-temperature induction
      using RNA-seq technology. A key flower bud differentiation associated gene, a
      homologue of FLORICAULA/LEAFY, was identified and named LcLFY (GenBank Accession
      No. KF008435). The cDNA sequence of LcLFY encodes a putative protein of 388 amino
      acids. To gain insight into the role of LcLFY, the temporal expression level of
      this gene was measured by real-time RT-PCR. LcLFY was highly expressed in flower
      buds and its expression correlated with the floral developmental stage.
      Heterologous expression of LcLFY in transgenic tobacco plants induced precocious
      flowering. Meantime, we investigated the sub-cellular localization of LcLFY. The
      LcLFY-Green fluorescent protein (GFP) fusion protein was found in the nucleus.
      The results suggest that LcLFY plays a pivotal role as a transcription factor in
      controlling the transition to flowering and in the development of floral organs
      in litchi.

PMID- 30218348
TI  - The effects of photobiomodulation therapy on mouse pre-osteoblast cell line MC3T3
      E1 proliferation and apoptosis via miR-503/Wnt3a pathway.
AB  - Photobiomodulation therapy (PBMT) has been demonstrated as regulating osteoblast
      proliferation. MicroRNAs (miRNAs) are involved in various pathophysiologic
      processes in osteoblast, but the role of miRNAs in the PBMT-based promotion of
      osteoblast proliferation remains unclear. This study aimed to investigate the
      effects of PBMT treatment (3.75 J/cm2) on mouse pre-osteoblast cell line MC3T3-E1
      proliferation and apoptosis via the miR-503/Wnt3a pathway; meanwhile, detect the
      expressions of miR-503 and Wnt3a after PBMT treatment and the role of miR-503 in
      regulating Wnt signaling molecules Wnt3a, beta-catenin, Runx2, apoptotic proteins
      caspase-3, and Bcl-2 in vitro. The PBMT parameters were as follows: 808 nm
      continuous wavelength, 0.401 W output power, 0.042 W/cm2 power density, 9.6 cm2
      spot size, 36 J energy, 3.75 J/cm2 energy density, 90 s irradiation for three
      times per 12 h, 14.5 cm distance of the laser source and the angle of divergence
      of the laser beam was 7 degrees . In our present study, the target relationship
      was predicted and verified by bioinformatics analysis and luciferase reporter
      assays. Gene mRNA and protein expressions were examined by qPCR and western blot
      analysis. The MTT method was used to evaluate the effect of miR-503 on MC3T3-E1
      cells proliferation. And cell apoptosis was examined by flow cytometry. The
      results showed that PBMT treatment reduced the expression of miR-503 and
      increased the level of Wnt3a (p < 0.01). Bioinformatics analysis and luciferase
      reporter assays revealed that Wnt3a was a target of miR-503, and Wnt3a was
      regulated by miR-503. Furthermore, miR-503 was found to functionally inhibit
      proliferation and promote apoptosis (p < 0.01). And during this process, Wnt3a,
      beta-catenin, Runx2, and Bcl-2 expressions were significantly inhibited (p <
      0.01); however, caspase-3 level was upregulated (p < 0.01). These results suggest
      that miR-503 plays a role in osteoblast proliferation and apoptosis in response
      to PBMT, which is potentially amenable to therapeutic manipulation for clinical
      application.

PMID- 30218347
TI  - Estimating the birth prevalence and pregnancy outcomes of congenital
      malformations worldwide.
AB  - Congenital anomaly registries have two main surveillance aims: firstly to define
      baseline epidemiology of important congenital anomalies to facilitate programme,
      policy and resource planning, and secondly to identify clusters of cases and any
      other epidemiological changes that could give early warning of environmental or
      infectious hazards. However, setting up a sustainable registry and surveillance
      system is resource-intensive requiring national infrastructure for recording all
      cases and diagnostic facilities to identify those malformations that that are not
      externally visible. Consequently, not all countries have yet established robust
      surveillance systems. For these countries, methods are needed to generate
      estimates of prevalence of these disorders which can act as a starting point for
      assessing disease burden and service implications. Here, we describe how registry
      data from high-income settings can be used for generating reference rates that
      can be used as provisional estimates for countries with little or no
      observational data on non-syndromic congenital malformations.

PMID- 30218349
TI  - The Effect of Ambient Light Conditions on Quantitative Pupillometry.
AB  - BACKGROUND: Automated devices collecting quantitative measurements of pupil size
      and reactivity are increasingly used for critically ill patients with
      neurological disease. However, there are limited data on the effect of ambient
      light conditions on pupil metrics in these patients. To address this issue, we
      tested the range of pupil reactivity in healthy volunteers and critically ill
      patients in both bright and dark conditions. METHODS: We measured quantitative
      pupil size and reactivity in seven healthy volunteers and seven critically ill
      patients with the Neuroptics-200 pupillometer in both bright and dark ambient
      lighting conditions. Bright conditions were created by overhead LED lighting in a
      room with ample natural light. Dark conditions consisted of a windowless room
      with no overhead light source. The primary outcome was the Neurological Pupil
      Index (NPi), a composite metric ranging from 0 to 5 in which > 3 is considered
      normal. Secondary outcomes included resting and constricted pupil size, change in
      pupil size, constriction velocity, dilation velocity, and latency. Results were
      analyzed with multi-level linear regression to account for both inter- and intra
      subject variability. RESULTS: Fourteen subjects underwent ten pupil readings each
      in bright and dark conditions, yielding 280 total measurements. In healthy
      subjects, median NPi in bright and dark conditions was 4.2 and 4.3, respectively.
      In critically ill subjects, median NPi was 2.85 and 3.3, respectively. Multi
      level linear regression demonstrated significant differences in pupil size, pupil
      size change, constriction velocity, and dilation velocity in various light levels
      in healthy patients, but not NPi. In the critically ill, NPi and pupil size
      change were significantly affected. CONCLUSION: Ambient light levels impact pupil
      parameters in both healthy and critically ill subjects. Changes in NPi under
      different light conditions are small and more consistent in healthy subjects, but
      significantly differ in the critically ill. Practitioners should standardize
      lighting conditions to maximize measurement reliability.

PMID- 30218350
TI  - Overexpressed in colorectal carcinoma gene (OCC-1) upregulation and APPL2 gene
      downregulation in breast cancer specimens.
AB  - Breast cancer is the most common cancer type and the second cause of cancer death
      in women. Different mechanisms are contributed to the initiation and progression
      of the breast cancer. OCC-1 and APPL2 neighboring genes located in 12q.23.3 human
      chromosome region are related to colorectal cancer. Here, we intended to
      investigate OCC-1 newly reported transcript variants and APPL2 gene expression
      alteration in breast cancer specimens and investigate OCC-1 variants
      overexpression effect on APPL2 and on cell cycle status. Rt-qPCR analysis
      indicated that the expression level of OCC-1A/B and OCC-1D (not OCC-1C)
      transcript variants has been increased while, APPL2 gene expression level has
      been decreased in breast cancer specimen, compared to their normal pairs.
      Therefore, a negative correlation of expression is evident between APPL2 and OCC
      1 genes in breast cancer specimen. Unlike OCC-1A/B which encodes a small protein,
      OCC-1D noncoding RNA overexpression lead to APPL2 downregulation in MCF7 cells.
      Consistently, OCC-1D overexpression resulted in increased sub-G1 cell population
      in MCF7 cells, detected by flow cytometry. Altogether, these results suggest that
      OCC1-D variant have an inhibitory effect on APPL2 expression and may regulate the
      cell cycle status.

PMID- 30218351
TI  - New polymorphic microsatellite loci revealed for the dusky shark Carcharhinus
      obscurus through Ion Proton double-digest RAD sequencing.
AB  - The non-model shark species, dusky shark Carcharhinus obscurus, is a bio
      economically and recreationally important shark in many areas of its range.
      Despite of the fishery importance of C. obscurus few genetic resources are
      currently available for the species. Here, we report on the isolation of eight
      novel microsatellite loci from C. obscurus using a double-digest restriction site
      associated DNA (RAD) sequencing approach on the Ion Proton semiconductor platform
      (ddRADseq-ion). We characterised the loci in 26 individuals and all loci were
      polymorphic, exhibiting 5-10 alleles (average 6.6), and observed and expected
      heterozygosities of 0.385-0.962 and 0.479-0.847, respectively. We found that all
      pairs of loci were in linkage equilibrium and conformed to Hardy-Weinberg
      expectations. The loci reported in this study are only the second set of
      microsatellite loci ever characterized for C. obscurus and will be valuable for
      molecular ecology studies for this vulnerable species.

PMID- 30218352
TI  - Effect of 5-aminolevulinic acid on the expression of carcinogenesis-related
      proteins in cultured primary hepatocytes.
AB  - Acute intermittent porphyria (AIP) is a heme pathway disorder caused by a
      decrease in the activity and synthesis of porphobilinogen deaminase. Thus, the
      first heme precursor 5-aminolevulinic acid (ALA) accumulates in the liver.
      Reactive oxygen species (ROS) resulting from ALA oxidation may be correlated to a
      higher incidence of hepatocellular carcinoma (HCC) in AIP patients. However, the
      molecular mechanisms of this relationship have not been thoroughly elucidated to
      date. In this study, we investigated the effect of increasing levels of ALA on
      the expression of proteins related to DNA repair, oxidative stress, apoptosis,
      proliferation and lipid metabolism. Primary rat hepatocytes were isolated by the
      collagenase perfusion method, lipoperoxidation was evaluated by a TBA
      fluorimetric assay and Western blotting was used to assess protein abundance. The
      data showed that ALA treatment promoted a dose-dependent increase of p53
      expression, downregulation of Bcl-2, HMG-CoA reductase and OGG1 and an increase
      in lipoperoxidation. There was no alteration in the expression of the
      transcription factor NF-kappaB, catalase and superoxide dismutase. ALA oxidation
      products induced protein regulation patterns, suggesting the interconnection of
      cellular processes, such as the intrinsic pathway of apoptosis, redox
      homeostasis, cell proliferation, lipid metabolism and DNA repair. This study
      helps to elucidate the molecular mechanisms of hepatotoxicity mediated by ALA pro
      oxidant effects and supports the hypothesis that ALA accumulation correlates with
      a higher incidence of hepatic carcinogenic events.

PMID- 30218353
TI  - Molecular mapping of aluminium resistance loci based on root re-growth and Al
      induced fluorescent signals (callose accumulation) in lentil (Lens culinaris
      Medikus).
AB  - Development of aluminium (Al) resistant genotypes through molecular breeding is a
      major approach for increasing seed yield under acidic conditions. There are no
      available reports on mapping of Al resistance loci and molecular breeding for Al
      resistant varieties in lentil. The present study reports a major quantitative
      trait loci (QTL) for Al resistance using simple sequence repeat (SSR) markers in
      F2 and F3 mapping populations derived from contrasting parents. Phenotypic
      response to Al was measured on the bases of root re-growth (RRG), fluorescent
      signals (callose accumulation) and Al contents in hydroponic assay. After
      screening 495 SSR markers to search polymorphism between two contrasting parents,
      73 polymorphic markers were used for bulk segregation analysis. Two major QTLs
      were identified using seven trait linked markers, one each for fluorescent
      signals and RRG mapped on linkage group (LG) 1 under Al stress conditions in F2
      mapping population of cross BM-4 * L-4602. One major QTL (qAlt_fs) was localised
      between PLC_88 and PBA_LC_373, covering 25.9 cM with adjacent marker PLC_88 at a
      distance of 0.4 cM. Another major QTL (qAlt_rrg) for RRG was in the marker
      interval of PBA_LC_1247 and PLC_51, covering a distance of 45.7 cM with nearest
      marker PBA_LC_1247 at a distance of 21.2 cM. Similarly, in F3 families of BM-4 *
      L-4602 and BM-4 * L-7903, LG-1 was extended to 285.9 and 216.4 cM respectively,
      having four newly developed genic-SSR markers. These QTLs had a logarithm of odd
      (LOD) value of 140.5 and 28.8 along with phenotypic variation of 52% and 11% for
      fluorescent signals and RRG respectively, whereas, qAlt_rrg had LOD of 36 and
      phenotypic variance of 25% in F3 population of BM-4 * L-4602. Two major QTLs
      identified in the present study can be further dissected for candidate gene
      discovery and development of molecular markers for breeding improved varieties
      with high Al resistance.

PMID- 30218354
TI  - Individualized alignment in total knee arthroplasty using image-based robotic
      assistance : Video article.
AB  - INTRODUCTION: Over the past decades many innovations were introduced in total
      knee arthroplasty (TKA) focusing on implant longevity and higher procedural
      precision; however, there are still a high number of dissatisfied patients. It
      was reported that better anatomical alignment may result in improved patient
      outcome; however, current technologies have limitations to achieve this. The aim
      of this video article is to describe the technique of individualized alignment in
      TKA with the use of image-based robotic assistance. METHODS: The technology is
      based on an individual patient knee model computed from segmented computed
      tomography (CT) scans. A preoperative planning of prosthesis position is
      conducted following the principle of kinematic alignment. Intraoperatively the
      soft tissue envelope is recorded and the computer predicts the gap balance based
      on the virtual planning. The prosthesis position is then adapted to achieve
      balanced gaps and to avoid soft tissue release. This technique is shown in a
      cadaver operation and clinical examples of two patients are described. RESULTS:
      With the combination of anatomically oriented prosthesis positioning and minor
      adaptations with respect to the soft tissue, an individualized alignment is
      achieved with reduced need of soft tissue release. The robotic-assisted surgery
      guarantees a precise implementation of the planning. The initial experience
      showed a promising outcome in short-term follow-up.

PMID- 30218355
TI  - Screening for Factors Involved in X Chromosome Inactivation Using Haploid ESCs.
AB  - Forward genetics can provide insight into molecular pathways as has been
      demonstrated by advances in cell biology from comprehensive genetic studies in
      simple organisms. Recently, techniques have become available that promise a
      similar potential for understanding developmental pathways in mammals. Here we
      describe a genetic forward screening approach for identifying factors involved in
      X chromosome inactivation that is based on haploid mouse embryonic stem cells.
      Using a genetically encoded selection system screening of large mutant pools can
      identify candidate silencing factors with high confidence.

PMID- 30218356
TI  - Unbiased Genetic Screen to Identify Factors Involved in X-Chromosome Inactivation
      Using a Pooled Bar-Coded shRNA Library.
AB  - In mammals, a dosage compensation mechanism exists to equalize gene expression
      levels between male and female. This process is initiated by Xist RNA, a long
      noncoding RNA that mediates the transcriptional silencing of a complete
      chromosome. The kinetics of events occurring on the future inactive X-chromosome
      has been described in detail over the last 20 years. More recently, parallel
      studies using advanced biochemical assays and genetic screens identified key
      factors critical for the silencing cascade. Here, we describe the procedure
      adopted in one of these studies, an shRNA-based loss-of-function screen in mouse
      embryonic stem cells (mESCs).The screen made use of a reporter cell line in which
      Xist-mediated silencing could be monitored by changes in GFP fluorescence. Loss
      of function was achieved using a custom made bar-coded pooled shRNA library. The
      screen aimed to identify shRNAs that lessen Xist mediated repression of the GFP
      reporter. The methods that were applied are of potential relevance for the
      development of related screens, for example to better understand how specific
      repressors silence one or several genes.

PMID- 30218357
TI  - ChIRP-MS: RNA-Directed Proteomic Discovery.
AB  - Comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP
      ms) is a novel technique for studying endogenous ribonucleoprotein complexes.
      ChIRP-ms is robust across a wide range of expression level, from abundant
      housekeeping RNAs (e.g., spliceosomal U RNAs) to relatively lowly expressed RNAs
      (e.g., Xist). In vivo RNA-protein interactions are chemically cross-linked, and
      purified using biotinylated antisense oligonucleotides against RNA of interest.
      Coprecipitated proteins are gently eluted, and identified by mass-spectrometry
      (for discovery) or by western blotting (for validation).

PMID- 30218358
TI  - Manipulation of Xist Imprinting in Mouse Preimplantation Embryos.
AB  - X-chromosome inactivation (XCI) is established in preimplantation embryos in
      mice. Prior to the establishment of XCI, expression of the long noncoding RNA
      (lncRNA) Xist is essential. Xist expression in mouse preimplantation embryos is
      imprinted, and paternal Xist is predominantly expressed. Due to the manner of
      imprinting, maternal Xist is always silenced. However, the nature of imprinting
      to repress maternal Xist is variable. For example, parthenogenetic embryos that
      are composed of two maternal genomes exhibit maternal Xist derepression during
      the preimplantation phases. Maintenance of Xist imprinting to repress maternal
      Xist depends on the chromatin condensation states and the dosage of Rnf12, an
      essential Xist activator. Therefore, alterations of chromatin states and Rnf12
      expression levels lead to maternal Xist derepression. In this chapter, we
      describe the method for derepressing maternal Xist by various approaches, such as
      mRNA injection, small molecule treatment, and nuclear transfer.

PMID- 30218359
TI  - Somatic Cell Nuclear Transfer in Mice: Basic Protocol and Its Modification for
      Correcting X Chromosome Inactivation Status.
AB  - Somatic cell nuclear transfer (SCNT) enables the production of animals from
      single cell nuclei. Unlike normally fertilized embryos, SCNT-derived embryos
      ectopically express the Xist gene from the maternal allele, because of the lack
      of Xist-repressing imprints in the somatic donor genome. This has severely
      compromised the development of SCNT-derived embryos, at least in mice. Here, we
      describe the basic protocol of mouse SCNT as well as a Xist knockdown SCNT
      procedure, which remarkably increases the efficiency of cloning mice.

PMID- 30218360
TI  - Live Imaging of Xist RNA.
AB  - Live imaging gives additional layers of information such as physical dynamics of
      a molecule of your interest. Aptamer-based green fluorescent protein (GFP)
      labeling is suitable for visualization of RNA molecules. Here we describe a
      method to visualize Xist RNA using the Bgl aptamer system.

PMID- 30218361
TI  - Live Imaging of X-Chromosome Inactivation and Reactivation Kinetics.
AB  - X-chromosome inactivation (XCI) is an epigenetic phenomenon that equalizes the
      number of X-linked gene products between male and female eutherian mammals by
      inactivating one of the two X chromosomes. XCI is essential for female mammalian
      development, and its failure can lead to embryonic death in mutant mice. The
      pattern of which X chromosome is inactivated changes dynamically during mouse
      embryogenesis, depending on developmental stages and tissues. Recent progress in
      molecular biology, including next-generation sequencing (NGS)-based analyses,
      enables the analysis of gene expression profiles at a single cell level. Combined
      with NGS technology, live imaging systems can now be used to track epigenetic
      events and clarify their casual and spatiotemporal relationships to cell
      differentiation and embryonic development. Here, I describe a novel live-cell
      imaging system based on "Momiji" mice for monitoring XCI at the single cell
      level.

PMID- 30218362
TI  - Visualizing the Dynamics of Inactive X Chromosomes in Living Cells Using Antibody
      Based Fluorescent Probes.
AB  - The inactive X chromosome (Xi) harbors characteristic epigenetic features,
      including the enrichment of histone H3 lysine 27 trimethylation (H3K27me3) and H4
      lysine 20 monomethylation (H4K20me1) as well as a lack of histone acetylation.
      Recently, these modifications have been visualized not only in fixed specimen,
      but also in living cells via probes derived from modification-specific
      antibodies. The probes include fluorescently labeled antigen binding fragments
      (Fabs), which can be loaded into cells, as well as genetically encoded single
      chain variable fragments tagged with the green fluorescent protein. We refer to
      the latter as modification specific intracellular antibodies, or "mintbodies" for
      short. By using Fabs or mintbodies to target Xi-specific modifications, the
      dynamics of Xi in living cells can be visualized.

PMID- 30218363
TI  - Visualization of Hidden Epitopes at the Inactive X Chromosome.
AB  - Immunodetection of nuclear antigens is often complicated by epitope masking, so
      that proteins known to function in the nucleus are sometimes not easily detected
      at their sites of action. Moreover, protein populations that are detected before
      unmasking can be very different to those seen after removal of nucleic acids.
      This is particularly true for components of the nuclear matrix, including those
      known to function at the inactive X chromosome. Here we describe an unmasking
      protocol that reveals previously undetected proteins at the inactive X chromosome
      in mouse fibroblasts.

PMID- 30218364
TI  - Chromosome Spread Analyses of Meiotic Sex Chromosome Inactivation.
AB  - A distinct form of X chromosome inactivation takes place during male meiosis,
      when the male sex chromosomes undergo a phenomenon known as meiotic sex
      chromosome inactivation (MSCI). MSCI is directed by DNA damage response signaling
      independent of Xist RNA to silence the transcriptional activity of the sex
      chromosomes, an essential event in male germ cell development. Here, we present
      protocols for the preparation and analyses of chromosome spread slides of mouse
      meiotic spermatocytes, thereby enabling a quick, inexpensive, and powerful
      cytological method to complement gene expression studies.

PMID- 30218365
TI  - Simultaneous RNA-DNA FISH in Mouse Preimplantation Embryos.
AB  - Fluorescent in situ hybridization (FISH) is a powerful cytogenetic technique that
      allows the visualization and quantification of RNA and DNA molecules in different
      cellular contexts. In general, FISH applications help to advance research,
      cytogenetics, and diagnostics. DNA FISH can be applied, for example, for gene
      mapping and for detecting genetic aberrations. RNA FISH provides information
      about gene expression. However, in cases where RNA and DNA molecules need to be
      detected in the same sample, the result is often compromised by the fact that the
      tissue sample is damaged due to the multitude of processing steps that are
      required for each application. In addition, the sequential application of RNA and
      DNA FISH protocols on the same sample is very time consuming. Here we describe a
      brief protocol that enables the combined and simultaneous detection of Xist RNA
      and centromeric DNA of chromosome 6 in mouse preimplantation embryos. In
      addition, we describe how to generate indirect-labeled probes starting from BACs.
      This protocol may be applied to any combination of RNA and DNA detection.

PMID- 30218366
TI  - Combined Immunofluorescence, RNA FISH, and DNA FISH in Preimplantation Mouse
      Embryos.
AB  - Transcriptional and epigenetic dynamics of the genome occur during early
      development in mammals. It has been difficult to study these dynamics due to the
      limitation of materials and the difficulty of handling. In this chapter, we
      describe our attempt to apply a combination of immunofluorescence (IF), and RNA
      and DNA fluorescent in situ hybridization (FISH) in preimplantation mouse
      embryos. We have concentrated on refining these techniques to study the dynamics
      of X chromosome inactivation in mouse embryos. The techniques and general
      underlying principles described here should be applicable to other mammals of
      interest.

PMID- 30218367
TI  - RNA-FISH and Immunofluorescence of Mouse Preimplantation and Postimplantation
      Embryos.
AB  - There are two modes of X chromosome inactivation (XCI) in the mouse. One mode is
      imprinted XCI: it is initiated at around the four-cell stage in favor of the
      paternal X chromosome, and is maintained in the extraembryonic tissues. The other
      mode is random XCI, which takes place in the epiblast lineage at the
      periimplantation stage. X-linked noncoding Xist RNA, which becomes upregulated on
      the X chromosome to be inactivated at the onset of XCI and plays a critical role
      in both imprinted and random XCI, and its accumulation in the nucleus have been
      referred to as one of the hallmarks of the presence of the inactivated X
      chromosome. RNA-FISH has therefore been an invaluable method for the study of
      XCI. As XCI status changes dynamically during periimplantation development in the
      mouse, analysis using samples from these developmental stages is absolutely
      necessary for elucidation of the molecular basis of XCI mechanisms. However,
      dissection of the embryos at around the periimplantation stages is not easy, and
      this impedes in vivo analysis of the kinetics of XCI. Here, we describe our
      methods for dissecting the periimplantation stage embryo and subsequent
      procedures for RNA-FISH and immunostaining.

PMID- 30218368
TI  - Experimental Analysis of Imprinted Mouse X-Chromosome Inactivation.
AB  - X-chromosome inactivation is a dosage compensation mechanism that equalizes X
      linked gene expression between male and female mammals through the
      transcriptional silencing of most genes on one of the two X-chromosomes in
      females. With a few key exceptions, once the X-chromosome is inactivated
      replicated copies of that X-chromosome are maintained as inactive in all
      descendant cells. X-inactivation is therefore a paradigm of epigenetic
      inheritance. Imprinted X-inactivation is a specialized form of X-inactivation
      that results in the silencing of the paternally derived X-chromosome. Due to its
      parent-of-origin-specific pattern of inactivation, imprinted X-inactivation is a
      model of mitotic as well as meiotic, i.e., transgenerational, epigenetic
      inheritance. All cells of the early mouse embryo undergo imprinted X
      inactivation, a pattern that is subsequently maintained in extraembryonic cell
      types in vivo and in vitro. Here, we describe both high- and low-throughput
      approaches to interrogate imprinted X-inactivation in the mouse embryo as well in
      cultured extraembryonic stem cells.

PMID- 30218369
TI  - X-Chromosome Inactivation and Escape from X Inactivation in Mouse.
AB  - X chromosome inactivation silences one X chromosome in female mammals. However,
      this silencing is incomplete, and some genes escape X inactivation. We describe
      methods to determine the chromosome-wide X inactivation status of genes in
      tissues or cell lines derived from mice using a combination of skewing of X
      inactivation and allele-specific analyses of gene expression based on RNA-seq.

PMID- 30218370
TI  - Practical Analysis of Hi-C Data: Generating A/B Compartment Profiles.
AB  - Recent advances in next-generation sequencing (NGS) and chromosome conformation
      capture (3C) analysis have led to the development of Hi-C, a genome-wide version
      of the 3C method. Hi-C has identified new levels of chromosome organization such
      as A/B compartments, topologically associating domains (TADs) as well as large
      megadomains on the inactive X chromosome, while allowing the identification of
      chromatin loops at the genome scale. Despite its powerfulness, Hi-C data analysis
      is much more involved compared to conventional NGS applications such as RNA-seq
      or ChIP-seq and requires many more steps. This presents a significant hurdle for
      those who wish to implement Hi-C technology into their laboratory. On the other
      hand, genomics data repository sites sometimes contain processed Hi-C data sets,
      allowing researchers to perform further analysis without the need for high-spec
      workstations and servers. In this chapter, we provide a detailed description on
      how to calculate A/B compartment profiles from processed Hi-C data on the
      autosomes and the active/inactive X chromosomes.

PMID- 30218371
TI  - Dharmic Religions and Health: A Holistic Analysis of Global Health Literature
      Related to Hinduism, Buddhism, Sikhism and Jainism.
AB  - Bibliometrics and scientometrics are popular and novel disciplines providing
      information in publication trends in a certain academic field. Although there has
      been an increasing popularity in bibliometric studies, a limited number of
      reports have been published in religion and health literature. In this study, to
      the best of our knowledge we aimed to perform a first bibliometric analysis in
      the health literature related to Dharmic religions, Hinduism, Buddhism, Sikhism
      and Jainism. We found a total of 655 health articles related to Dharmic religions
      as we searched Web of Science databases. The United States of America (USA)
      ranked first in Health and Hinduism literature with 62 documents followed by
      India, the UK and Bangladesh (n = 40, 33 and 6, respectively). A detailed keyword
      analysis revealed that the most used keywords in the field of Hinduism and health
      were "Hinduism," "religion," "spirituality" and "Islam." The USA was also the
      leading county in the literature of Buddhism and Health with 159 articles
      (32.78%) and followed by Thailand, the UK and China (10.72, 6.8 and 6.39%,
      respectively). The Journal of Religion and Health was noted to be the most
      prolific source in this field. We found that the developing countries such as
      India, Thailand, Singapore and Taiwan were found to be included in the most
      productive countries list on the contrary to previous bibliometric studies in
      health and religion field.

PMID- 30218372
TI  - The Effect of Religious Intervention Using Prayer for Quality of Life and
      Psychological Status of Patients with Permanent Pacemaker.
AB  - The development of heart disease, followed by the pacemaker implantation, has
      reduced the quality and psychological problems for patients. Thus, the present
      study was conducted to determine the effect of prayer on the quality of life and
      the psychological status of patients with permanent pacemaker. This is a quasi
      experimental study in which 75 patients were assigned to experimental and control
      groups. Religious intervention was conducted for the experimental group,
      including the Tavasol prayer and four recommended (mustahab) remembrances in 7
      sessions. Before and after the intervention, the patients were provided with the
      quality of life questionnaire and psychological status. Then, the questionnaires
      were analyzed using descriptive and analytical tests. Before intervention, there
      was no difference between quality of life status and psychological status of
      patients, but after intervention, their quality of life increased and their
      psychological status improved significantly. The implementation of religious
      intervention based on prayer positively affects the quality of life and
      psychological status of patients; thus, implementing this intervention is
      necessary for patients.

PMID- 30218373
TI  - [First diagnosis of systemic sclerosis based on ocular complications].
AB  - BACKGROUND: Systemic sclerosis is a chronic connective tissue disease in which
      immune system dysfunction alters the structure and function of blood vessels. It
      is characterized by enhanced tissue fibrosis, which may rapidly affect a large
      area of the skin as well as internal organs. Dry eye symptoms are the most common
      ocular findings. CASE REPORT: This case presents a 51-year-old male patient
      suffering from blurred vision in the left eye. The ophthalmoscopic examination
      revealed retinal thrombotic microangiopathy in both eyes. Spectral-domain optical
      coherence tomography (SD OCT) showed a macular edema in the left eye. Although
      these ocular symptoms do not represent the initial manifestation of the primary
      disease, correct diagnosis was only made in the context of the retinal findings.
      CONCLUSION: Retinal microangiopathic lesions can play a seminal role in
      diagnosing systemic sclerosis.

PMID- 30218374
TI  - NAD metabolism and the SLC34 family: evidence for a liver-kidney axis regulating
      inorganic phosphate.
AB  - The solute carrier 34 (SLC34) family of membrane transporters is a major
      contributor to Pi homeostasis. Many factors are involved in regulating the SLC34
      family. The roles of the bone mineral metabolism factors parathyroid hormone
      (PTH) and fibroblast growth factor 23 (FGF23) in Pi homeostasis are well studied.
      Intracellular Pi is thought to be involved in energy metabolism, such as ATP
      production. Under certain conditions of altered energy metabolism, plasma Pi
      concentrations are affected by the regulation of a Pi shift into cells or release
      from the tissues. We recently investigated the mechanism of hepatectomy-related
      hypophosphatemia, which is thought to involve an unknown phosphaturic factor.
      Hepatectomy-related hypophosphatemia is due to impaired nicotinamide adenine
      dinucleotide (NAD) metabolism through its effects on the SLC34 family in the
      liver-kidney axis. The oxidized form of NAD, NAD+, is an essential cofactor in
      various cellular biochemical reactions. Levels of NAD+ and its reduced form NADH
      vary with the availability of dietary energy and nutrients. Nicotinamide
      phosphoribosyltransferase (Nampt) generates a key NAD+ intermediate, nicotinamide
      mononucleotide, from nicotinamide and 5-phosphoribosyl 1-pyrophosphate. The
      liver, an important organ of NAD metabolism, is thought to release metabolic
      products such as nicotinamide and may control NAD metabolism in other organs.
      Moreover, NAD is an important regulator of the circadian rhythm. Liver-specific
      Nampt-deficient mice and heterozygous Nampt mice have abnormal daily plasma Pi
      concentration oscillations. These data indicate that NAD metabolism in the
      intestine, liver, and kidney is closely related to Pi metabolism through the
      SLC34 family. Here, we review the relationship between the SLC34 family and NAD
      metabolism based on our recent studies.

PMID- 30218375
TI  - Implementation of fed-batch strategies for vitamin K (menaquinone-7) production
      by Bacillus subtilis natto in biofilm reactors.
AB  - Recent studies show the essential health benefits associated with vitamin K,
      especially menaquinone-7 (MK-7). These benefits include reducing risks of
      cardiovascular diseases, osteoporosis, and even cancer. However, MK-7 production
      on an industrial level is only possible through bacterial fermentation and also
      current static fermentation strategies are not potent enough with difficulties to
      scale up. Biofilm reactors, however, may be a practical alternative. Biofilm
      reactors provide a controlled environment for the microorganisms to form mature
      and robust biofilms that enable them to produce value-added products with
      enhanced efficiencies. In this study, fed-batch addition of glucose and glycerol
      were investigated to the base media in biofilm reactors, as carbon source
      addition seemed crucial in batch fermentations. Results indicated that fed-batch
      strategies can be significantly effective in glucose-based medium, increasing the
      end-product concentrations to 28.7 +/- 0.3 mg/L of MK-7 which was 2.3 fold higher
      than the level produced in suspended-cell bioreactors and renders the biofilm
      reactors as a potential replacement for static fermentation strategies. Moreover,
      morphological changes of B. subtilis were tracked during the 12-day long
      fermentation runs and finally, SEM investigations confirmed significant biofilm
      and extracellular matrices formed on the plastic composite support (PCS) in the
      biofilm reactors. In conclusion, biofilm reactors especially with fed-batch
      fermentation regimes seem to be an effective tool for MK-7 production at
      industrial scales.

PMID- 30218376
TI  - Biochar carrier application for nitrogen removal of domestic WWTPs in winter:
      challenges and opportunities.
AB  - Biofilm processes have a better nitrogen removal ability than traditional
      activated sludge at low temperatures (< 15  degrees C). Many biofilm processes,
      as well as integrated biofilm and activated sludge processes, are potential and
      realizable nitrogen removal upgrading methods for domestic wastewater treatment
      plants (WWTPs). Therefore, biofilm packing material is attractive for domestic
      WWTP upgrading and reconstruction in winter. For a half decade, researchers have
      successfully applied activated carbon to biochar as biofilm carrier in the
      wastewater treatment field. Biochar, as a biostable soil amendment with pores and
      crevices on its surface, has been applied in the soil-plant system, which
      promoted the adsorption of NH4+ and NO3-, decreased N2O emission, transcriptional
      level of narG, nxrA, and nirS, and changed the microbial community composition
      for better nitrogen removal. However, in the field of wastewater treatment, the
      study of biochar-packed process is merely in the laboratory stage of simulated
      wastewater, which deserves further research in the future. In this mini review,
      we will discuss the performances of different processes at low temperatures, the
      related mechanism of the biochar-packed process for nitrogen removal, and other
      potential applications of biochar carriers.

PMID- 30218377
TI  - Enhanced production of phenolic compounds in hairy root cultures of Polygonum
      multiflorum and its metabolite discrimination using HPLC and FT-IR methods.
AB  - Hairy root cultures (HRCs) are characterized by fast and unlimited root growth,
      and they have greater genetic stability than other cultivation methods. HRCs are
      known to accumulate phytochemical levels comparable to those of intact plant. In
      this study, HRCs of Polygonum multiflorum were established from leaf explants
      infected with Agrobacterium rhizogenes strain KCCM 11879. Over 60% of the
      explants showed hairy root induction after 21 days of cultivation on hormone-free
      MS (Murashige and Skoog Physiol Plant 15:473-479, 1962) medium; induced roots
      were confirmed by PCR using a rolC-specific primer. Of the six lines of HRCs
      selected for further analysis, line HR-01 performed best, producing a root
      biomass (105.2 g L-1 of FW, 9.7 g L-1 of DW), which is 10-fold higher than that
      of non-transgenic roots. The HR-01 line also showed a significant increase in its
      total phenolic content (26.64 mg g-1 DW), while non-transgenic roots accumulated
      8.36 mg g-1 DW of total phenolic. The levels of phenolic compounds in the HRCs
      increased more than 2.5-fold following exposure to 50 MUM methyl jasmonate for 5
      days. Fourier transform infrared (FT-IR) spectroscopic analysis of bioactive
      accumulation in P. multiflorum enabled discrimination between hairy root and
      adventitious root cultures. Thus, it is evident from this study that HRCs could
      be an attractive proposition for large-scale production of root biomass and
      secondary metabolites of P. multiflorum in bioreactors.

PMID- 30218378
TI  - Synthetic biology approaches to access renewable carbon source utilization in
      Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum (C. glutamicum), an important industrial workhorse, is
      capable of efficiently producing a variety of value-added chemicals and fuels
      beyond amino acids. C. glutamicum has a broad natural substrate spectrum and can
      simultaneously utilize various carbon sources in blends. The substrate spectrum
      of C. glutamicum has been further extended by detailed knowledge of carbon core
      metabolism and well-established genetic tools and engineering strategies. At
      present, many pathways have been successfully engineered in C. glutamicum for
      access to alternative renewable sources to produce natural or non-natural
      products, making C. glutamicum a promising and favorable microbial cell factory.
      In this review, we mainly focus on synthetic biology and metabolic engineering
      strategies for developing synthetic strains that grow on renewable sources to
      produce the target products. At the same time, we also explore the promotion and
      future challenges of existing synthetic biology platforms for industrial platform
      microorganism metabolic engineering efforts.

PMID- 30218379
TI  - Pyrroloquinoline quinone-dependent dehydrogenases of acetic acid bacteria.
AB  - Pyrroloquinoline quinone (PQQ)-dependent dehydrogenases (quinoproteins) of acetic
      acid bacteria (AAB), such as the membrane-bound alcohol dehydrogenase (ADH) and
      the membrane-bound glucose dehydrogenase, contain PQQ as the prosthetic group.
      Most of them are located on the periplasmic surface of the cytoplasmic membrane,
      and function as primary dehydrogenases in cognate substance-oxidizing respiratory
      chains. Here, we have provided an overview on the function and molecular
      architecture of AAB quinoproteins, which can be categorized into six groups
      according to the primary amino acid sequences. Based on the genomic data, we
      discuss the types of quinoproteins found in AAB genome and how they are
      distributed. Our analyses indicate that a significant number of uncharacterized
      orphan quinoproteins are present in AAB. By reviewing recent experimental
      developments, we discuss how to characterize the as-yet-unknown enzymes.
      Moreover, our bioinformatics studies also provide insights on how quinoproteins
      have developed into intricate enzymes. ADH comprises at least two subunits: the
      quinoprotein dehydrogenase subunit encoded by adhA and the cytochrome subunit
      encoded by adhB, and the genes are located in a polycistronic transcriptional
      unit. Findings on stand-alone derivatives of adhA encourage us to speculate on a
      possible route for ADH development in the evolutional history of AAB. A
      combination of bioinformatics studies on big genome sequencing data and wet
      studies assisted with genetic engineering would unravel biochemical functions and
      physiological role of uncharacterized quinoproteins in AAB, or even in
      unculturable metagenome.

PMID- 30218381
TI  - Linking obesity-induced leptin-signaling pathways to common endocrine-related
      cancers in women.
AB  - Obesity is related to many major diseases and cancers. Women have higher rates of
      obesity and obesity is linked to commonly occurring cancers in women. However,
      there is a lack of knowledge of the unique mechanism(s) involved in each type of
      cancer. The objective of this review is to highlight the need for novel
      experimental approaches and a better understanding of the common and unique
      pathways to resolve controversies regarding the role of obesity in cancer. In
      women, there is a link between hormones and obesity-associated genes in cancer
      development. Leptin is an obesity-associated gene that has been studied
      extensively in cancers; however, whether the defect is in the leptin gene or in
      its signaling pathways remains unclear. Both leptin and its receptor have been
      positively correlated with cancer progression in some endocrine-related cancers
      in women. This review offers an up-to-date and cohesive review of both upstream
      and downstream pathways of leptin signaling in cancer and a comprehensive picture
      of cancer pathogenesis in light of current evidence of leptin effects in several
      major types of cancer. This work is intended to aid in the design of better
      therapeutic strategies for obese/overweight women with cancer.

PMID- 30218380
TI  - In-hospital care, complications, and 4-month mortality following a hip or
      proximal femur fracture: the Spanish registry of osteoporotic femur fractures
      prospective cohort study.
AB  - : We have characterised 997 hip fracture patients from a representative 45
      Spanish hospitals, and followed them up prospectively for up to 4 months. Despite
      suboptimal surgical delays (average 59.1 hours), in-hospital mortality was lower
      than in Northern European cohorts. The secondary fracture prevention gap is
      unacceptably high at 85%. PURPOSE: To characterise inpatient care, complications,
      and 4-month mortality following a hip or proximal femur fracture in Spain.
      METHODS: Design: prospective cohort study. Consecutive sample of patients >= 50
      years old admitted in a representative 45 hospitals for a hip or proximal femur
      fragility fracture, from June 2014 to June 2016 and followed up for 4 months post
      fracture. Patient characteristics, site of fracture, in-patient care (including
      secondary fracture prevention) and complications, and 4-month mortality are
      described. RESULTS: A total of 997 subjects (765 women) of mean (standard
      deviation) age 83.6 (8.4) years were included. Previous history of fracture/s
      (36.9%) and falls (43%) were common, and 10-year FRAX-estimated major and hip
      fracture risks were 15.2% (9.0%) and 8.5% (7.6%) respectively. Inter-trochanteric
      (44.6%) and displaced intra-capsular (28.0%) were the most common fracture sites,
      and fixation with short intramedullary nail (38.6%) with spinal anaesthesia
      (75.5%) the most common procedures. Surgery and rehabilitation were initiated
      within a mean 59.1 (56.7) and 61.9 (55.1) hours respectively, and average length
      of stay was 11.5 (9.3) days. Antithrombotic and antibiotic prophylaxis were given
      to 99.8% and 98.2% respectively, whilst only 12.4% received secondary fracture
      prevention at discharge. Common complications included delirium (36.1 %) and
      kidney failure (14.1%), with in-hospital and 4-month mortality of 2.1% and 11%
      respectively. CONCLUSIONS: Despite suboptimal surgical delay, post-hip fracture
      mortality is low in Spanish hospitals. The secondary fracture prevention gap is
      unacceptably high at > 85%, in spite of virtually universal anti-thrombotic and
      antibiotic prophylaxis.

PMID- 30218383
TI  - Validation of a Sequential Organ Failure Assessment Score using Electronic Health
      Record Data.
AB  - The sequential organ failure assessment (SOFA) score is a scoring system commonly
      used in critical care to assess severity of illness. Automated calculation of the
      SOFA score using existing electronic health record data would broaden its
      applicability. We performed a manual validation of an automated SOFA score
      previously developed at our institution. A retrospective analysis of a random
      subset of 300 patients from a previously published randomized trial of critically
      ill adults was performed, with manual validation of SOFA scores from the date of
      initial intensive care unit admission. Spearman's rank correlation coefficient,
      weighted Cohen's kappa, and Bland-Altman plots were used to assess agreement
      between manual and electronic versions of SOFA scores and between manual and
      electronic versions of their individual components. There was high agreement
      between manual and electronic SOFA scores (Spearman's rank correlation
      coefficient = 0.90, 95% CI 0.87-0.93). Renal and respiratory components had lower
      agreement (weighted Cohen's kappa = 0.63, 95% CI 0.53-0.73 for renal; weighted
      Cohen's kappa = 0.77, 95% CI 0.70-0.84 for respiratory). The area under the
      receiver operating characteristic curve (AUC) for 30-day in-hospital mortality
      was 0.77 (95% CI 0.68-0.84) for manual SOFA scores and 0.75 (95% CI 0.66-0.83)
      for automated SOFA scores. Automatic calculation of SOFA scores from the
      electronic health record is feasible and correlates highly with manually
      calculated SOFA scores. Both have similar predictive value for 30-day in-hospital
      mortality.

PMID- 30218382
TI  - Imaging of distant metastases of prostate cancer.
AB  - The detection of distant metastases at the initial diagnosis of prostate cancer
      (PCa) establishes the treatment approach and has a prognostic value, nevertheless
      it is not well established. Since proposed staging approaches often contradict
      each other, we aimed to compare the current imaging techniques for staging of
      advanced PCa, including future applications of the most innovative methods.
      Conventional imaging techniques, including computed tomography (CT), magnetic
      resonance imaging (MRI), and positron emission tomography (PET) have been
      employed for metastatic staging (both N and M staging) of men with high-risk PCa,
      but surgical pelvic dissection remains the gold standard for N staging. However,
      functional MRI by using diffusion-weighted imaging, MR lymphography (MRL) with
      ultra-small paramagnetic iron oxide particles (USPIO), and hybrid PET/MRI imaging
      showed both high sensitivity and high specificity for nodal staging and depicting
      metastases. The standard of practice for M staging in PCa includes the
      radionuclide bone scan and targeted X-ray film, but their performance has
      generally been poor. Recently, MRI showed promising results with applications in
      both local and distant staging. Finally, with the development of new PET tracers,
      PET/CT and PET/MRI offer a combination of excellent pharmacokinetic
      characteristics, functional information, and precise anatomic localization and
      morphological correlation of tumor lesions.

PMID- 30218384
TI  - Functional characterization and expression analysis of two terpene synthases
      involved in floral scent formation in Lilium 'Siberia'.
AB  - MAIN CONCLUSION: Floral scent formation in Lilium 'Siberia' is mainly due to
      monoterpene presence in the floral profile. LoTPS1 and LoTPS3 are responsible for
      the formation of (+/-)-linalool and beta-ocimene in Lilium 'Siberia'. Lilium
      'Siberia' is a perennial herbaceous plant belonging to Liliaceae family,
      cultivated both as a cut flower and garden plant. The snowy white flower emits a
      pleasant aroma which is mainly caused by monoterpenes present in the floral
      volatile profile. Previously terpene synthase (TPS) genes have been isolated and
      characterized from various plant species but less have been identified from
      Liliaceae family. Here, two terpene synthase genes (LoTPS1 and LoTPS3), which are
      highly expressed in sepals and petals of Lilium 'Siberia' flower were
      functionally characterized recombinant LoTPS1 specifically catalyzes the
      formation of (Z)-beta-ocimene and (+/-)-linalool as its main volatile compounds
      from geranyl pyrophosphate (GPP), whereas LoTPS3 is a promiscuous monoterpene
      synthase which utilizes both GPP and farnesyl pyrophosphate (FPP) as a substrate
      to generate (+/-)-linalool and cis-nerolidol, respectively. Transcript levels of
      both genes were prominent in flowering parts, especially in sepals and petals
      which are the main source of floral scent production. The gas chromatography-mass
      spectrometry (GC-MS) and quantitative real-time PCR analysis revealed that the
      compounds were emitted throughout the day, prominently during the daytime and
      lower levels at night following a strong circadian rhythm in their emission
      pattern. Regarding mechanical wounding, both genes showed considerable
      involvement in floral defense by inducing the emission of (Z)-beta-ocimene and
      (+/-)-linalool, elevating the transcript accumulation of LoTPS1 and LoTPS3.
      Furthermore, the subcellular localization experiment revealed that LoTPS1 was
      localized in plastids, whilst LoTPS3 in mitochondria. Our findings on these two
      TPSs characterized from Lilium 'Siberia' provide new insights into molecular
      mechanisms of terpene biosynthesis in this species and also provide an
      opportunity for biotechnological modification of floral scent profile of Lilium.

PMID- 30218385
TI  - Evaluation of vestibular system with vHIT in industrial workers with noise
      induced hearing loss.
AB  - PURPOSE: Industrial workers are frequently exposed to noise and the noise can
      cause hearing loss. The relationship between vestibular abnormalities and long
      term exposure to occupational noise has been reported. The aim of this study was
      to use vHIT (video head impulse test) to evaluate the semicircular canal's
      function in industrial workers with noise-induced hearing loss. METHODS: In the
      present study, we included 36 male patients (aged 28-55 years, mean 44.4 +/- 6.1
      years) with hearing loss due to noise exposure from working in the steel and
      metal industry for at least 4 years, and a control group of 30 healthy men (aged
      34-50 years, mean 41.1 +/- 4.5 years) without hearing loss. The gain of the
      vestibulo-ocular reflex for all 6 semicircular canals was examined by vHIT in 66
      patients. RESULTS: Canal deficit was detected in 20 (55.5%) of 36 patients in the
      noise exposure hearing loss group and was detected in 2 (6.6%) of 30 participants
      in the control group. There was significant loss of capacity for VOR gain in
      patients with noise exposure hearing loss. CONCLUSIONS: In the present study we
      found that exposure to noise can cause vestibular dysfunction. And the vHIT is
      easily applicable, quick and practical and can individually evaluate all
      semicircular channels. Therefore, to evaluate vestibular function with vHIT is
      quick and practical.

PMID- 30218386
TI  - Endoscopic management of paediatric meningoencephaloceles: a case series.
AB  - INTRODUCTION: Congenital meningoencephaloceles represent a rare clinical entity,
      with its frequency being around 1 out of 4000-5000 live births. They usually
      present as a midline mass and the differential diagnosis includes dermoids,
      encephaloceles, and gliomas. Although the standard coronal approach with frontal
      craniotomy and pericranial flap has been considered the preferred method for
      several years, it is associated with risks and prolonged hospitalization. The
      endoscopic procedure is gaining ground and we are aiming to present our
      experience from five cases that were treated endoscopically. MATERIALS AND
      METHODS: Five cases of paediatric meningoencephaloceles (age ranging from 2.5 to
      10 years) were treated in our department between the years 2007-2017. Four
      children had a congenital and one child a post-traumatic meningoencephalocele.
      The presenting symptoms included nasal obstruction, meningitis and CSF leak. All
      patients had pre-operative imaging with CT and MRI scans and the preferred method
      of repair was multi-layered closure. RESULTS: All our patients had uneventful
      recovery, without any post-operative complications. The follow-up period ranges
      from 39 to 98 months. All five patients remain asymptomatic and recurrence-free.
      CONCLUSION: Endoscopic management of paediatric meningoencephaloceles is a
      reliable and safe approach and it is known to have no adverse effects on facial
      growth. It carries a satisfactory success rate, reduces the in-hospital stay with
      lower cost of treatment, better cosmesis and lower morbidity than external
      procedures. It requires multidisciplinary team setting in a tertiary centre with
      experienced endoscopic anterior skull base surgeons. Pre-operative assessment and
      post-operative care are of paramount importance and larger series need to be
      studied to reach safe conclusions and establish management guidelines.

PMID- 30218387
TI  - Role of leptin in allergic rhinitis during sublingual immunotherapy.
AB  - OBJECTIVE: Increasing evidence suggests that leptin is upregulated during
      allergic reactions in the airway and related to the severity of disease in
      allergic rhinitis (AR). In this study, we aimed to investigate the expression of
      leptin during sublingual immunotherapy (SLIT) in AR patients. METHODS: Forty AR
      patients without obesity were recruited in this study. Twenty patients received
      house dust mite (HDM) allergen extract for SLIT and twenty patients received
      placebo randomly. Protein expression of leptin in serum and nasal lavage was
      tested by enzyme-linked immuno sorbent assay (ELISA) 1 and 2 years after SLIT
      treatment, respectively. Peripheral blood mononuclear cells (PBMCs) and human
      nasal epithelial cell were prepared and stimulated by recombinant leptin after 24
      months' SLIT treatment and the induction of Th2 cytokines (IL-4/IL-5/IL-13) were
      detected by ELISA. RESULTS: SLIT treatment decreased the expression of leptin
      protein in serum and nasal lavage significantly compared with placebo group 1 and
      2 years after SLIT treatment. Nasal leptin level was correlated to decreased Th2
      response (IL-4/IL-5/IL-13) and enhanced Treg (IL-10/TGF-beat) response after 2
      years' SLIT. We also found that SLIT decreased the ability of leptin in promoting
      Th2 cytokines expression by PBMCs and human nasal epithelial cell after 2 years'
      SLIT treatment. CONCLUSION: Changes of leptin expression in serum and nasal
      lavage may be correlated with Th2/Treg regulation during SLIT. Our results
      suggested that leptin served as an important biomarker during SLIT.

PMID- 30218388
TI  - Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma
      with PSMA-Targeted [18F]DCFPyL PET/CT.
AB  - PURPOSE: To investigate the utility of prostate-specific membrane antigen (PSMA)
      targeted [18F]DCFPyL positron emission tomography (PET)/X-ray computed tomography
      (CT) imaging for the detection of sites of disease in patients with metastatic
      non-clear cell renal cell carcinoma (RCC). PROCEDURES: Eight patients with
      metastatic non-clear cell RCC underwent imaging with PSMA-targeted [18F]DCFPyL
      PET/CT. Imaged RCC histologic subtypes included papillary RCC (n = 3),
      chromophobe RCC (n = 2), unclassified RCC (n = 2), and Xp11 translocation RCC (n
      = 1). Using comparison to conventional CT and/or magnetic resonance imaging as
      reference, two radiologists with expertise in nuclear medicine identified
      putative sites of disease on [18F]DCFPyL PET/CT and classified each lesion as
      having no radiotracer uptake, equivocal uptake, or definitive uptake. RESUTS: In
      total, 73 metastatic sites and 3 primary tumors compatible with sites of non
      clear cell RCC were identified on conventional imaging. Metastatic sites of
      disease included lymph nodes (n = 40), venous thrombi (n = 3), pulmonary nodules
      (n = 10), bone lesions (n = 15), brain lesions (n = 3), and retroperitoneal
      masses (n = 2). Only 10 of the 73 lesions (13.7 %) were classified as having
      definitive radiotracer uptake (median SUVmax = 3.25, range = 1.2-9.5), 14 lesions
      (19.2 %) had equivocal uptake (median SUVmax = 2.85, range = 0.5-6.5), and 49
      lesions (67.1 %) had no definitive uptake above background (median SUVmax = 1.7,
      range = 0.2-3.0). The three primary renal tumors demonstrated lower radiotracer
      avidity relative to surrounding normal renal parenchyma. CONCLUSIONS: A small
      proportion of sites of non-clear cell RCC showed uptake of the PSMA-targeted
      radiotracer [18F]DCFPyL. Unlike for clear cell RCC, the results of this study
      indicate that PSMA-based PET is not appropriate for imaging other RCC subtypes.

PMID- 30218389
TI  - Predictive Value of [18F]ML-10 PET/CT in Early Response Evaluation of Combination
      Radiotherapy with Cetuximab on Nasopharyngeal Carcinoma.
AB  - PURPOSE: Apoptosis may be an indication of success therapy, and precise detection
      of apoptosis can provide instructional suggestions in the therapy management of
      malignant tumors. PROCEDURES: We used CNE-1 cell lines for in vitro experiments,
      and colony formation assay, CCK-8 assay, cell apoptosis analysis, and western
      blotting were performed. For in vivo experiments, subcutaneous xenotransplanted
      tumor models of CNE-1 in nude mice were established. Then, small animal positron
      emission tomography/X-ray computed tomography (PET/CT) images were acquired by
      tail intravenous injection of 2-(5-[18F]fluoropentyl)-2-methyl-malonic acid
      ([18F]ML-10) or 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) before and 24 h and 48
      h after treatment. Moreover, expression of epidermal growth factor receptor
      (EGFR), Ki-67, Glut-1, and terminal deoxynucleotidyl transferase-mediated dUTP
      nick end labeling (TUNEL) was examined by immunohistochemical examination. Tumor
      volumes of mice were recorded every 2 days. RESULTS: In the presence of
      Cetuximab, the number of colonies of CNE-1 cells decreased significantly after
      irradiation at 1 and 2 Gy. In addition, Cetuximab increased the radiation-induced
      cytotoxicity and apoptosis of CNE-1 cells. Mechanistic studies demonstrated that
      Cetuximab enhanced radiosensitivity by suppressing the EGFR/PI3-K/AKT pathway. In
      PET/CT imaging, the tumors showed clear uptake of [18F]ML-10 at 24 h and 48 h
      after combined treatment, and the value of tumor/muscle (T/M) and SUVmax (the max
      of standard uptake value) was significantly higher than those of the other three
      groups. The T/M of [18F]ML-10 uptake showed a positive correlation of 0.926 with
      the apoptosis index (P < 0.001). However, the uptake of [18F]FDG in tumors
      exhibited no trend among the four groups. The T/M of [18F]FDG revealed a positive
      correlation of 0.926 with Glut-1 intensity (P < 0.001). CONCLUSIONS: Our work
      revealed that Cetuximab could increase the radiosensitivity of CNE-1 cells both
      in vitro and in vivo. Apoptosis imaging with [18F]ML-10 PET/CT is a promising
      modality for application in the response prediction of nasopharyngeal carcinoma.

PMID- 30218390
TI  - Paradigms in Fluorescence Molecular Imaging: Maximizing Measurement of Biological
      Changes in Disease, Therapeutic Efficacy, and Toxicology/Safety.
AB  - Fluorescence molecular imaging (MI) is an important concept in preclinical
      research that focuses on the visualization of cellular and biological function in
      a non-invasive fashion to better understand in vivo disease processes and
      treatment effects. MI differs fundamentally from traditional preclinical imaging
      strategies in that it generally relies on reporter probes specific for particular
      targets or pathways that can be used to reveal biological changes in situ, at the
      site(s) of disease. In contrast, the more established imaging modalities, like
      magnetic resonance imaging, X-ray, micro X-ray computed tomography, and
      ultrasound, historically have relied primarily on late-stage anatomical or
      physiologic changes. The practical application of fluorescence MI, however, has
      drifted somewhat from the emphasis on quantifying biology, and based on the
      publication record, it now appears to include any imaging in which a probe or
      contrast agent is used to non-invasively acquire in vivo endpoint information.
      Unfortunately, the mere use of a defined biologically specific probe, in the
      absence of careful study design, does not guarantee that any useful biological
      information is actually gained, although often useful endpoint results still can
      be achieved. This review proposes to add subcategories of MI, termed MI
      biological assessment (or MIBA), that emphasize a focus on obtaining early and
      clear biological changes associated with disease development, therapeutic
      efficacy, and drug-induced tissue changes. Proper selection of probes and careful
      study design are critical for maximizing the non-invasive assessment of in vivo
      biological changes, and applications of these critical elements are described.

PMID- 30218392
TI  - Somatic complaints in children and adolescents with social anxiety disorder.
AB  - BACKGROUND: Associations of social anxiety disorder (SAD) with various somatic
      symptoms have been already reported in the literature several times. The present
      study investigated somatic complaints in children and adolescents with SAD
      compared to controls and evaluated the relationship between social anxiety and
      somatic symptom severity. METHODS: Thirty children and adolescents with SAD were
      compared with 36 healthy age-matched controls. Self-reported fears were assessed
      using the Phobiefragebogen fur Kinder und Jugendliche (PHOKI); emotional and
      behavioral problems were assessed using the Child Behavior Checklist (CBCL/4-18);
      and the Giebetaener Beschwerdebogen fur Kinder und Jugendliche (GBB-KJ) was used
      to assess 59 somatic symptoms. RESULTS: Parents and youth with SAD reported
      higher somatic symptom severity compared to controls. Youth with SAD more
      frequently reported stomach pain, circulatory complaints, and fatigue than
      controls. Specific group differences between SAD and control youth were found for
      the following single somatic symptoms: faintness, quickly exhausted, sensation of
      heat, stomachache, nausea, dizziness, and sudden heart complaints. Parents of
      girls with SAD reported higher somatic symptom severity than parents of boys with
      SAD. CONCLUSIONS: The results demonstrated a significant positive association
      between somatic symptoms and social anxiety in youth. The results of the present
      study can help to develop improved screening measurements, which increase the
      proportion of children and adolescents with SAD receiving proper treatment.

PMID- 30218391
TI  - Molecular Pathways in Melanomagenesis: What We Learned from Next-Generation
      Sequencing Approaches.
AB  - PURPOSE OF REVIEW: Conventional clinico-pathological features in melanoma
      patients should be integrated with new molecular diagnostic, predictive, and
      prognostic factors coming from the expanding genomic profiles. Cutaneous melanoma
      (CM), even differing in biological behavior according to sun-exposure levels on
      the skin areas where it arises, is molecularly heterogeneous. The next-generation
      sequencing (NGS) approaches are providing data on mutation landscapes in driver
      genes that may account for distinct pathogenetic mechanisms and pathways. The
      purpose was to group and classify all somatic driver mutations observed in the
      main NGS-based studies. RECENT FINDINGS: Whole exome and whole genome sequencing
      approaches have provided data on spectrum and distribution of genetic and genomic
      alterations as well as allowed to discover new cancer genes underlying CM
      pathogenesis. After evaluating the mutational status in a cohort of 686 CM cases
      from the most representative NGS studies, three molecular CM subtypes were
      proposed: BRAFmut, RASmut, and non-BRAFmut/non-RASmut.

PMID- 30218393
TI  - Can Population Modelling Principles be Used to Identify Key PBPK Parameters for
      Paediatric Clearance Predictions? An Innovative Application of Optimal Design
      Theory.
AB  - PURPOSE: Physiologically-based pharmacokinetic (PBPK) models are essential in
      drug development, but require parameters that are not always obtainable. We
      developed a methodology to investigate the feasibility and requirements for
      precise and accurate estimation of PBPK parameters using population modelling of
      clinical data and illustrate this for two key PBPK parameters for hepatic
      metabolic clearance, namely whole liver unbound intrinsic clearance (CLint,u,WL)
      and hepatic blood flow (Qh) in children. METHODS: First, structural
      identifiability was enabled through re-parametrization and the definition of
      essential trial design components. Subsequently, requirements for the trial
      components to yield precise estimation of the PBPK parameters and their inter
      individual variability were established using a novel application of population
      optimal design theory. Finally, the performance of the proposed trial design was
      assessed using stochastic simulation and estimation. RESULTS: Precise estimation
      of CLint,u,WL and Qh and their inter-individual variability was found to require
      a trial with two drugs, of which one has an extraction ratio (ER) <= 0.27 and the
      other has an ER >= 0.93. The proposed clinical trial design was found to lead to
      precise and accurate parameter estimates and was robust to parameter uncertainty.
      CONCLUSION: The proposed framework can be applied to other PBPK parameters and
      facilitate the development of PBPK models.

PMID- 30218395
TI  - Electroencephalogram (EEG) for children with autism spectrum disorder: evidential
      considerations for routine screening.
AB  - Routine electroencephalograms (EEG) are not recommended as a screen for epileptic
      discharges (EDs) in current practice guidelines for children with autism spectrum
      disorder (ASD). However, a review of the research from the last three decades
      suggests that this practice should be reevaluated. The significant comorbidity
      between epilepsy and ASD, its shared biological pathways, risk for developmental
      regression, and cognitive challenges demand increased clinical investigation
      requiring a proactive approach. This review highlights and explains the need for
      screening EEGs for children with ASD. EEG would assist in differentiating EDs
      from core features of ASD and could be included in a comprehensive assessment.
      EEG also meets the demand for evidence-based precision medicine and focused care
      for the individual, especially when overlapping processes of development are
      present.

PMID- 30218396
TI  - Horizontal gaze palsy with progressive scoliosis: is scoliosis linked to ROBO3
      mutations?

PMID- 30218394
TI  - Early Trajectory Prediction in Elite Athletes.
AB  - Cerebellar plasticity is a critical mechanism for optimal feedback control. While
      Purkinje cell activity of the oculomotor vermis predicts eye movement speed and
      direction, more lateral areas of the cerebellum may play a role in more complex
      tasks, including decision-making. It is still under question how this motor
      cognitive functional dichotomy between medial and lateral areas of the cerebellum
      plays a role in optimal feedback control. Here we show that elite athletes
      subjected to a trajectory prediction, go/no-go task manifest superior subsecond
      trajectory prediction accompanied by optimal eye movements and changes in
      cognitive load dynamics. Moreover, while interacting with the cerebral cortex,
      both the medial and lateral cerebellar networks are prominently activated during
      the fast feedback stage of the task, regardless of whether or not a motor
      response was required for the correct response. Our results show that cortico
      cerebellar interactions are widespread during dynamic feedback and that
      experience can result in superior task-specific decision skills.

PMID- 30218397
TI  - Clinical management of Duchenne muscular dystrophy: the state of the art.
AB  - INTRODUCTION: Duchenne muscular dystrophy (DMD) is a devastating, progressive
      neuromuscular disorder for which there is no cure. As the dystrophin gene is
      located on the X chromosome, DMD occurs predominately in males. DMD is caused by
      a lack of functional dystrophin protein resulting from mutations in the 2.2-Mb
      DMD gene, whichdisrupts the reading frame. Care considerations for DMD advocate a
      coordinated, multidisciplinary approach to the management of DMD in order to
      optimize management of the primary manifestations of DMD as well as any secondary
      complications that may arise. METHODS: This review provides an overview of the
      multidisciplinary clinical management of DMD with regard to the respiratory,
      cardiology, orthopedic, and nutritional needs of patients with DMD. Recent
      advances in novel disease-modifying treatments for DMD are also discussed with
      specific reference to exon skipping and suppression of premature stop codons as
      promising genetic therapies. RESULTS: The combination of multidisciplinary
      clinical management alongside novel gene therapiesoffers physicians a powerful
      armamentarium for the treatment of DMD.

PMID- 30218398
TI  - L-Arginine prevents stroke-like episodes but not brain atrophy: a 20-year follow
      up of a MELAS patient.

PMID- 30218399
TI  - Towards zero waste production in the paint industry wastewater using an agro
      based material in the treatment train.
AB  - An attempt has been made to evaluate the use of natural, agro-based material,
      Moringa oleifera as a coagulant in the treatment of recreated water-based paint
      effluent. The treatment train sequence comprising coagulation, flocculation,
      sedimentation, sand filtration, and membrane filtration was used. The efficiency
      was evaluated in terms of color and turbidity. The influence of experimental
      parameters such as eluent type, eluent concentration, coagulant dose, coagulant
      eluate volume, initial effluent pH, and initial effluent concentration was
      examined. The recommended conditions to yield maximum removal efficiency are 80
      mL of eluate prepared using 3 g of M. oleifera seed powder and 1 N NaCl, under
      actual pH, to treat a liter of effluent. The treated supernatant from coagulation
      unit was passed through a sand filtration setup and a membrane filtration, with a
      maximum removal of color above 95%. The results affirmed the positive coagulation
      properties of M. oleifera, which could serve as a better alternative for chemical
      coagulant. The optimized treatment conditions derived for the recreated paint
      effluent were applied in the real paint effluent treatment. An opportunity was
      identified for re-using treated wastewater, as a cooling fluid and a diluting
      agent for lower quality paints.The results affirmed the positive coagulation
      properties of M. oleifera, which could serve as a better alternative for chemical
      coagulant. Graphical abstract ?.

PMID- 30218400
TI  - Molecular Association of Glia Maturation Factor with the Autophagic Machinery in
      Rat Dopaminergic Neurons: a Role for Endoplasmic Reticulum Stress and MAPK
      Activation.
AB  - Parkinson's disease (PD) is one of the several neurodegenerative diseases where
      accumulation of aggregated proteins like alpha-synuclein occurs. Dysfunction in
      autophagy leading to this protein build-up and subsequent dopaminergic
      neurodegeneration may be one of the causes of PD. The mechanisms that impair
      autophagy remain poorly understood. 1-Methyl-4-phenylpiridium ion (MPP+) is a
      neurotoxin that induces experimental PD in vitro. Our studies have shown that
      glia maturation factor (GMF), a brain-localized inflammatory protein, induces
      dopaminergic neurodegeneration in PD and that suppression of GMF prevents MPP+
      induced loss of dopaminergic neurons. In the present study, we demonstrate a
      molecular action of GMF on the autophagic machinery resulting in dopaminergic
      neuronal loss and propose GMF-mediated autophagic dysfunction as one of the
      contributing factors in PD progression. Using dopaminergic N27 neurons, primary
      neurons from wild type (WT), and GMF-deficient (GMF-KO) mice, we show that GMF
      and MPP+ enhanced expression of MAPKs increased the mammalian target of rapamycin
      (mTOR) activation and endoplasmic reticulum stress markers such as phospho
      eukaryotic translation initiation factor 2 alpha kinase 3 (p-PERK) and inositol
      requiring enzyme 1alpha (IRE1alpha). Further, GMF and MPP+ reduced Beclin 1,
      focal adhesion kinase (FAK) family-interacting protein of 200 kD (FIP200), and
      autophagy-related proteins (ATGs) 3, 5, 7, 16L, and 12. The combined results
      demonstrate that GMF affects autophagy through autophagosome formation with
      significantly reduced lysosomal-associated membrane protein 1/2, and the number
      of autophagic acidic vesicles. Using primary neurons, we show that MPP+ treatment
      leads to differential expression and localization of p62/sequestosome and in GMF
      KO neurons, there was a marked increase in p62 staining implying autophagy
      deficiency with very little co-localization of alpha-synuclein and p62 as
      compared with WT neurons. Collectively, this study provides a bidirectional role
      for GMF in executing dopaminergic neuronal death mediated by autophagy that is
      relevant to PD.

PMID- 30218401
TI  - Correction to: Overexpression of Protein Kinase Inhibitor Alpha Reverses Rat Low
      Voluntary Running Behavior.
AB  - The original version of this article unfortunately contained mistake in Table 2
      to where two directionality arrows were inverted.

PMID- 30218402
TI  - Employers' Perspectives on Accommodating and Retaining Employees with Newly
      Acquired Disabilities: An Exploratory Study.
AB  - Introduction Timely and appropriate accommodations can help employees who
      experience disabilities stay at work instead of exiting the labor force.
      Employers can play a critical role in connecting such workers with the
      accommodations they need. This qualitative study seeks to inform policy makers
      who want to improve workforce retention outcomes by uncovering factors that
      affect whether employers provide accommodations to, and ultimately retain,
      employees with disabilities. Methods We conducted semistructured interviews with
      a convenience sample of human resources professionals in 14 Arkansas-based
      employers, yielding detailed information on 50 cases in which an employee
      developed or disclosed a disability. We analyzed the interviews using a grounded
      theory approach and compared cases to identify key themes emerging across
      subgroups of cases. Results Two organization-level factors and four employee
      level factors influenced employers' efforts to accommodate and retain employees
      with disabilities: employer resources; employers' communication with the employee
      and other stakeholders; employee tenure; employee work performance;
      active/sedentary nature of employee role; and the severity and type of employees'
      health conditions. Conclusions Consistent with prior literature, employers with
      greater access to resources and better ability to communicate generally made
      greater effort to accommodate and retain employees with disabilities. However,
      employers in the study did not deploy these resources and processes consistently
      when making decisions about whether and how to provide accommodations to workers
      with disabilities; employee-level characteristics affected their actions. Policy
      makers should consider intervention approaches that reach workers who may be
      overlooked by employers with scarce resources.

PMID- 30218403
TI  - The Beta-Hydroxybutyrate Suppresses the Migration of Glioma Cells by Inhibition
      of NLRP3 Inflammasome.
AB  - Activation of inflammasome leads to the formation of an inflammatory
      microenvironment which plays an important role in the process of cancer
      development. Beta-hydroxybutyrate (BHB) is a ketone body that has recently been
      reported to exert anti-inflammatory effects via inhibition of NOD-like receptor
      pyrin domain-containing 3 (NLRP3) inflammasome. Here, we investigated the
      potential influence of BHB on the in vitro migration of C6 glioma cells and the
      activation of NLRP3 inflammasome. Our results indicated that administration of
      BHB suppressed C6 cells migration and NLRP3 inflammasome activation, reducing the
      levels of activated cysteinyl aspartate-specific proteinase 1 (caspase-1) and
      mature Interleukin 1beta (IL-1beta). Fully activation of NLRP3 inflammasome was
      induced by lipopolysaccharide (LPS) prime plus adenosine triphosphate (ATP)
      stimulation in C6 cells, which promoted in vitro migration of C6 cell. BHB also
      counteracted the LPS/ATP-promoted cell migration by suppressing the activation of
      caspase-1 and the maturation of IL-1beta. The enhancement of phospho-signal
      transducer and activator of transcription 3 (p-STAT3), degradation of nuclear
      factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
      (IkappaBalpha) as well as the overexpression of fibroblast growth factor 2 (FGF2)
      resulting from LPS/ATP treatment, and subsequent IL-1beta maturation could also
      be compensated by BHB. Our results suggested that BHB inhibits the activation of
      NLRP3 inflammasome in C6 glioma cells and consequently suppressed the C6 cell
      migration. These findings also implicated that by inhibiting NLRP3 inflammasome,
      BHB reduced the inflammatory microenvironment which provided ancillary
      therapeutic benefits for the intervention of glioma.

PMID- 30218404
TI  - A Novel Microfluidic Device-Based Neurite Outgrowth Inhibition Assay Reveals the
      Neurite Outgrowth-Promoting Activity of Tropomyosin Tpm3.1 in Hippocampal
      Neurons.
AB  - Overcoming neurite inhibition is integral for restoring neuronal connectivity
      after CNS injury. Actin dynamics are critical for neurite growth cone formation
      and extension. The tropomyosin family of proteins is a regarded as master
      regulator of actin dynamics. This study investigates tropomyosin isoform 3.1
      (Tpm3.1) as a potential candidate for overcoming an inhibitory substrate, as it
      is known to influence neurite branching and outgrowth. We designed a microfluidic
      device that enables neurons to be grown adjacent to an inhibitory substrate, Nogo
      66. Results show that neurons, overexpressing hTpm3.1, have an increased
      propensity to overcome Nogo-66 inhibition. We propose Tpm3.1 as a potential
      target for promoting neurite growth in an inhibitory environment in the central
      nervous system.

PMID- 30218405
TI  - Superoxide Formation in Cardiac Mitochondria and Effect of Phenolic Antioxidants.
AB  - Since mitochondria are the main cellular source of reactive oxygen species, it is
      important to study the effect of dietary phenolic compounds on the level of ROS
      in these organelles. Using the EPR spectroscopy and TIRON probe, the ability of
      the investigated phenols (quercetin, rutin, caffeic acid, curcumin, and
      resveratrol) to scavenge superoxide anion radicals generated by isolated heart
      mitochondria of Wistar rats under variable oxygen partial pressure was studied.
      It was shown that during a 10 min incubation, caffeic acid in concentrations of
      10-500 MUM most effectively scavenged superoxide radicals formed in the complex
      III of the mitochondrial respiratory chain. A comparable antioxidant effect of
      rutin under these experimental conditions was observed at higher concentrations
      of 1-10 mM. The antioxidant activity of quercetin in the concentration range of
      10-500 MUM during the first minutes of incubation was higher than that of caffeic
      acid. Of the phenolic compounds studied, curcumin had the least effect on the
      superoxide radicals.

PMID- 30218406
TI  - Prevalence of sarcopenia and 9-year mortality in nursing home residents.
AB  - BACKGROUND: Sarcopenia is a progressive loss of muscle mass, strength, and
      function. It is linked to functional decline, and secondary to this, to nursing
      home admission. AIMS: To look into the prevalence of sarcopenia in a nursing home
      population and to gain insight into the relation of sarcopenia with mortality in
      this cohort. METHODS: A longitudinal cohort follow-up started in October 2007 in
      52 nursing homes in Belgium. Following data were procured: anthropometrics
      (weight/length), body composition (muscle mass through bio-impedance
      absorptiometry, BIA), functional status (Katz), nutritional status (mini
      nutritional assessment-short form, MNA), and a number of laboratory parameters.
      RESULTS: In total, 745 residents were included. Mean age was 84.6 +/- 7.2 years.
      Mean follow-up time was 1632 +/- 1026 days. In total, 17% had severe sarcopenia,
      45% had moderate sarcopenia, and 38% had no sarcopenia. Following items were
      significant (p < 0.05) on univariate analysis with mortality as outcome:
      sarcopenia, gender, BMI, skeletal muscle mass, age, MNA, and functional level. In
      multivariate analysis, only MNA, skeletal muscle mass, and age were still
      significant. Odds ratio for skeletal muscle mass was 1.171 for the highest
      percentile group, 2.277 for the middle percentile group, and 4.842 for the lowest
      percentile group. DISCUSSION: The prevalence of sarcopenia was higher than in
      comparative literature, for which there are a few hypotheses. Cut-off values for
      sarcopenia using BIA for specific cohorts need to be re-evaluated. CONCLUSIONS:
      It seems to remain useful to screen for muscle mass in institutionalized elderly,
      because there is a clear and significant correlation with long-term mortality.

PMID- 30218407
TI  - Hypofractionated stereotactic radiotherapy for oligometastatic patients:
      developing of a response predictive model.
AB  - OBJECTIVES: Treatment of oligometastatic patients is a current challenge in
      radiation oncology. Aim of this study is to define a dose-response relationship
      for hypofractionated radiotherapy of oligometastases. METHODS: Retrospective
      analysis of metastases treated by hypofractionated stereotactic radiotherapy was
      performed. Delivered dose was calculated both as biological effective dose
      (BED10), and as ratio between BED10 and the logarithm of metastasis volume (BED10
      logVolume Ratio, BVR). Two dose-response models were defined by logistic
      regression. The fitted outcome was the Metastases Complete Response (MCR).
      Performances of the models were assessed by area under the receiver operating
      curve (AUC) and by bootstrap calibration of original data. BED10 and BVR impact
      on survival outcomes has been evaluated. RESULTS: Fifty-three patients with 79
      metastases were analyzed. AUC and calibration of BVR-based logistic model showed
      better accuracy in predicting MCR with respect to BED10-based model. No
      significant difference between the two ROCs was observed (De Long test p value >
      0.05), but significant discordance in calibration resulted in the BED10 model (p
      value < 0.05 in Hosmer-Lemeshow Goodness of fit test). BVR returned also better
      results in multivariate analyses for survival outcomes. CONCLUSIONS: The ratio
      between BED10 and the logarithm of metastasis volume (BVR), as a corrective
      factor for fitting the probability of metastases response to stereotactic
      radiotherapy, could be a tool for evaluating and prescribing treatments for
      oligometastatic disease. BVR can be useful for producing more reliable survival
      statistics too.

PMID- 30218408
TI  - Can one detect atrial fibrillation using a wrist-type photoplethysmographic
      device?
AB  - This study aims at evaluating the potential of a wrist-type photoplethysmographic
      (PPG) device to discriminate between atrial fibrillation (AF) and other types of
      rhythm. Data from 17 patients undergoing catheter ablation of various arrhythmias
      were processed. ECGs were used as ground truth and annotated for the following
      types of rhythm: sinus rhythm (SR), AF, and ventricular arrhythmias (VA). A total
      of 381/1370/415 10-s epochs were obtained for the three categories, respectively.
      After pre-processing and removal of segments corresponding to motion artifacts,
      two different types of feature were derived from the PPG signals: the interbeat
      interval-based features and the wave-based features, consisting of
      complexity/organization measures that were computed either from the PPG waveform
      itself or from its power spectral density. Decision trees were used to assess the
      discriminative capacity of the proposed features. Three classification schemes
      were investigated: AF against SR, AF against VA, and AF against (SR&VA). The best
      results were achieved by combining all features. Accuracies of 98.1/95.9/95.0 %,
      specificities of 92.4/88.7/92.8 %, and sensitivities of 99.7/98.1/96.2 % were
      obtained for the three aforementioned classification schemes, respectively.
      Graphical Abstract Atrial fibrillation detection using PPG signals.

PMID- 30218409
TI  - Laboratory automation reduces time to report of positive blood cultures and
      improves management of patients with bloodstream infection.
AB  - The impact on time to results (TTR) and clinical decisions was evaluated for mono
      microbial positive blood cultures (BC) processed using the BD Kiestra Work Cell
      Automation (WCA) system. Positive BC were processed by the WCA system by full
      automatic subculture on solid media and digital imaging after 8 h of incubation
      (8-h method) followed by identification (ID) and antimicrobial susceptibility
      testing (AST). To evaluate the accuracy of the 8-h method, ID and AST from 8-h
      and overnight incubated colonies were compared for the same organisms. To
      evaluate its clinical impact, results from 102 BC processed by the 8-h method
      (cases) were compared with those from 100 BC processed by overnight incubation
      method (controls) in a comparable period. Identification after 8-h and overnight
      incubation gave concordant results in 101/102 (99.0%) isolates. Among a total of
      1379 microorganism-antimicrobial combinations, categorical agreement was 99.4%
      (1371/1379); no very major error, 7 major errors, and one minor error were
      observed. TTR in cases (32.8 h +/- 8.3 h) was significantly (p < 0.001) shorter
      than in controls (55.4 h +/- 13.3 h). A significant reduction was observed for
      duration of empirical therapy (cases 54.8 h +/- 23.3 h vs controls 86.9 h +/-
      34.1 h, p < 0.001) and 30-day crude mortality rate (cases 16.7% vs controls
      29.0%, p < 0.037). Automation and 8-h digital reading of plates from positive BC,
      followed by ID and AST, greatly reduce TTR and shorten the duration of
      antimicrobial empiric therapy, possibly improving outcome in patients with mono
      microbial bloodstream infections.

PMID- 30218410
TI  - Effects of Neostigmine and Sugammadex for Reversal of Neuromuscular Blockade on
      QT Dispersion Under Propofol Anesthesia: A Randomized Controlled Trial.
AB  - INTRODUCTION: Reversal of non-depolarizing neuromuscular blocking agent
      neostigmine is associated with QT prolongation under general anesthesia. To
      clarify the effects of neostigmine and sugammadex on hemodynamic status, the QT
      interval and QT dispersion after reversal of neuromuscular blockade were
      evaluated with a 12-lead electrocardiogram. To exclude QT prolongation due to
      sevoflurane, the present study was performed under propofol anesthesia. METHODS:
      After receiving approval from the ethics committee of Dokkyo Medical University
      Hospital, 40 patients with American Society of Anesthesiologists physical status
      I or II were randomly allocated to group N (n = 20) or group S (n = 20). Group N
      was administered neostigmine (40 MUg/kg) and atropine (20 MUg/kg), while Group S
      was administered sugammadex (4 mg/kg) for reversal of neuromuscular blockade
      after surgery. The changes in RR interval, QT interval (QT), corrected QT
      interval (QTc), QT dispersion (QTD), and corrected QT dispersion (QTcD) before
      and after administration of reversal agents were recorded using computerized
      measurements. Statistical analysis was performed using two-way analysis of
      variance. RESULTS: The RR interval significantly decreased after reversal of the
      neuromuscular blockade in group N, compared with group S (p < 0.05). Compared
      with group S, the QT decreased, whereas QTc and QTcD increased, in group N (p <
      0.05). Sugammadex was not found to alter QT, QTc, QTD, or QTcD throughout the
      study. CONCLUSION: In the present study, a mixture of neostigmine and atropine,
      but not sugammadex, increased QTc and QTcD under propofol anesthesia. Thus,
      neostigmine may cause electrocardiogram abnormalities that could precede the
      development of fatal arrhythmias.

PMID- 30218411
TI  - Correlations between CYP3A4 polymorphism and susceptibility to breast cancer in
      Chinese Han population.
AB  - BACKGROUND: CYP3A4 is a major enzyme catalyzing the metabolism of endogenous
      steroids that play an important role in the etiology of carcinogenesis. This
      study was designed to investigate the contribution of CYP3A4 polymorphism to
      breast cancer in Chinese Han female population. METHODS: To examine whether
      variants of CYP3A4 contribute to breast cancer, 5 single-nucleotide polymorphisms
      (SNPs) of CYP3A4 were genotyped by Sequenom MassARRAY in 267 breast cancer
      patients and 302 healthy controls. Odds ratio (OR) and 95% confidence intervals
      (CIs) were calculated by unconditional logistic regression adjusted for age.
      RESULTS: We found that the TT genotype of CYP3A4*1G (rs2242480) polymorphism was
      associated with increased risk of breast cancer using the fixed effects model
      (recessive model: OR = 2.34, p = 0.018). Stratified according to age, CYP3A4*1G
      increased the risk of breast cancer especially in less than 50-year-old group
      (codominant model OR = 3.68, p = 0.041; recessive model: OR = 3.55, p = 0.012).
      Furthermore, TT genotype of rs2242480 was associated with Cerb-B2 positive
      (recessive model: OR = 2.47, p = 0.025) and stage I/II (recessive model: OR =
      2.32, p = 0.041). However, no statistically significant associations in other
      polymorphisms and haploview analysis were observed. CONCLUSIONS: This study
      provides an evidence for polymorphism of CYP3A4 gene associated with the
      development of breast cancer, also a new insight into etiology of breast cancer.
      However, the underlying mechanism of the CYP3A4 gene in breast cancer is
      necessary for further study.

PMID- 30218412
TI  - Burden of cardiovascular disease in Japanese cancer patients and survivors: a
      single cancer-center study in Niigata City.
AB  - BACKGROUND: Cardiovascular disease (CVD) and cancer are major causes of death in
      Japan. As most CVDs are chronic and often aggravate, long-term follow-up is
      necessary. Although some cancer patients and survivors have CVD, its prognostic
      significance and prevalence are unknown. Therefore, we conducted a retrospective
      study at our center to determine the prevalence of cancer patients with CVD.
      METHODS: In 2015, our 10-year (2005-2014) cancer registry was summarized.
      Comorbidities including left ventricular dysfunction, atrial fibrillation (AF),
      ischemic heart disease, aortic stenosis, venous thromboembolism (VTE), and
      elevation of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were
      examined. RESULTS: In total, 26,235 de novo cancer patients were registered and
      16,130 survived until January 1, 2015. The 5-year survival rate was 64.0% for all
      cancer patients and 44.2% for cancer patients with CVD. Cox proportional hazards
      analysis adjusting for age, cancer stage, and body mass index revealed that AF
      [hazard ratio (HR) 1.219, male; P = 0.038], VTE (HR 1.517, male; P = 0.003 and HR
      2.089, female; P < 0.001), and NT-proBNP elevation (HR 1.861, female; P = 0.002)
      were significantly associated with death. The CVD prevalence among cancer
      survivors in 2015 was 8.7% vs 3.5% for males vs females. AF was the most common
      CVD (prevalence: male, 4.0%; female, 1.0%). The prevalence of most CVD in adults
      increased progressively with age, with male predominance (12.1% for male and 7.5%
      for female patients in the 80 s age group). CONCLUSIONS: One in 10 elderly cancer
      survivors has serious CVD. AF, VTE, and heart failure were critical
      comorbidities. Cardiologists and cancer-care providers should recognize CVD
      presence and monitor patients closely, providing medications or interventions
      concurrently with cancer therapy.

PMID- 30218413
TI  - Multiscale divergence between Landsat- and lidar-based biomass mapping is related
      to regional variation in canopy cover and composition.
AB  - BACKGROUND: Satellite-based aboveground forest biomass maps commonly form the
      basis of forest biomass and carbon stock mapping and monitoring, but biomass maps
      likely vary in performance by region and as a function of spatial scale of
      aggregation. Assessing such variability is not possible with spatially-sparse
      vegetation plot networks. In the current study, our objective was to determine
      whether high-resolution lidar-based and moderate-resolution Landsat-base
      aboveground live forest biomass maps converged on similar predictions at stand-
      to landscape-levels (10 s to 100 s ha) and whether such differences depended on
      biophysical setting. Specifically, we examined deviations between lidar- and
      Landsat-based biomass mapping methods across scales and ecoregions using a
      measure of error (normalized root mean square deviation), a measure of the
      unsystematic deviations, or noise (Pearson correlation coefficient), and two
      measures related to systematic deviations, or biases (intercept and slope of a
      regression between the two sets of predictions). RESULTS: Compared to forest
      inventory data (0.81-ha aggregate-level), lidar and Landsat-based mean biomass
      predictions exhibited similar performance, though lidar predictions exhibited
      less normalized root mean square deviation than Landsat when compared with the
      reference plot data. Across aggregate-levels, the intercepts and slopes of
      regression equations describing the relationships between lidar- and Landsat
      based biomass predictions stabilized (i.e., little additional change with
      increasing area of aggregates) at aggregate-levels between 10 and 100 ha,
      suggesting a consistent relationship between the two maps at landscape-scales.
      Differences between lidar- and Landsat-based biomass maps varied as a function of
      forest canopy heterogeneity and composition, with systematic deviations
      (regression intercepts) increasing with mean canopy cover and hardwood proportion
      within forests and correlations decreasing with hardwood proportion. CONCLUSIONS:
      Deviations between lidar- and Landsat-based maps indicated that satellite-based
      approaches may represent general gradients in forest biomass. Ecoregion impacted
      deviations between lidar and Landsat biomass maps, highlighting the importance of
      biophysical setting in determining biomass map performance across aggregate
      scales. Therefore, regardless of the source of remote sensing (e.g., Landsat vs.
      lidar), factors affecting the measurement and prediction of forest biomass, such
      as species composition, need to be taken into account whether one is estimating
      biomass at the plot, stand, or landscape scale.

PMID- 30218414
TI  - Octreotide treatment for neonatal chylothorax.

PMID- 30218417
TI  - What price semiparametric Cox regression?
AB  - Cox's proportional hazards regression model is the standard method for modelling
      censored life-time data with covariates. In its standard form, this method relies
      on a semiparametric proportional hazards structure, leaving the baseline
      unspecified. Naturally, specifying a parametric model also for the baseline
      hazard, leading to fully parametric Cox models, will be more efficient when the
      parametric model is correct, or close to correct. The aim of this paper is two
      fold. (a) We compare parametric and semiparametric models in terms of their
      asymptotic relative efficiencies when estimating different quantities. We find
      that for some quantities the gain of restricting the model space is substantial,
      while it is negligible for others. (b) To deal with such selection in practice we
      develop certain focused and averaged focused information criteria (FIC and AFIC).
      These aim at selecting the most appropriate proportional hazards models for given
      purposes. Our methodology applies also to the simpler case without covariates,
      when comparing Kaplan-Meier and Nelson-Aalen estimators to parametric
      counterparts. Applications to real data are also provided, along with analyses of
      theoretical behavioural aspects of our methods.

PMID- 30218416
TI  - Extrapolation of praziquantel pharmacokinetics to a pediatric population: a
      cautionary tale.
AB  - L-praziquantel (PZQ) pharmacokinetic data were analyzed from two relative
      bioavailability Phase 1 studies in adult, healthy subjects with two new oral
      dispersion tablet (ODT) formulations of L-PZQ administered under various
      combinations of co-administration with food, water, and/or crushing. Linear mixed
      effects models adequately characterized the noncompartmental estimates of the
      pharmacokinetic profiles in both studies. Dose, food, and formulation were found
      to significantly affect L-PZQ exposure in both studies. The model for AUC was
      then extrapolated to children 2-5 years old accounting for enzyme maturation and
      weight. The predicted exposures were compared to an external Phase 1 study
      conducted by the Swiss Tropical and Public Health Institute using a currently
      marketed formulation (Cesol 600 mg immediate-release tablets) and found to be
      substantially lower than observed. A root cause analysis was completed to
      identify the reason for failure of the models. Various scenarios were proposed
      and tested. Two possible reasons for the failure were identified. One reason was
      that the model did not account for the reduced hepatic clearance seen in patients
      compared to the healthy volunteer population used to build the model. The second
      possible reason was that PZQ absorption appears sensitive to meal composition and
      the model did not account for differences in meals between a standardized Phase 1
      unit and clinical sites in Africa. Further studies are needed to confirm our
      hypotheses.

PMID- 30218418
TI  - Defining causal meditation with a longitudinal mediator and a survival outcome.
AB  - In the context of causal mediation analysis, prevailing notions of direct and
      indirect effects are based on nested counterfactuals. These can be problematic
      regarding interpretation and identifiability especially when the mediator is a
      time-dependent process and the outcome is survival or, more generally, a time-to
      event outcome. We propose and discuss an alternative definition of mediated
      effects that does not suffer from these problems, and is more transparent than
      the current alternatives. Our proposal is based on the extended graphical
      approach of Robins and Richardson (in: Shrout (ed) Causality and psychopathology:
      finding the determinants of disorders and their cures, Oxford University Press,
      Oxford, 2011), where treatment is decomposed into different components, or
      aspects, along different causal paths corresponding to real world mechanisms.
      This is an interesting alternative motivation for any causal mediation setting,
      but especially for survival outcomes. We give assumptions allowing
      identifiability of such alternative mediated effects leading to the familiar
      mediation g-formula (Robins in Math Model 7:1393, 1986); this implies that a
      number of available methods of estimation can be applied.

PMID- 30218415
TI  - Two decades of off-label prescribing in children: a literature review.
AB  - BACKGROUND: In the past two decades, many legislative and regulatory initiatives
      were taken globally to improve drug use in children. However, children are still
      found to be prescribed with off-label drugs. This study was conducted to provide
      an overview of the worldwide trend in off-label prescribing in children from the
      year 1996 to 2016. DATA SOURCES: The articles published in PubMed, MEDLINE and
      Google Scholar were searched using text words: off-label, unlicensed, paediatric
      and children. Additional articles were identified by reviewing the bibliography
      of the retrieved articles. Full-text articles published in English which reported
      on the prevalence of off-label prescribing in children between January 1996 and
      December 2016 were included. RESULTS: A total of 101 studies met the inclusion
      criteria. Off-label prescribing definition included four main categories: age,
      indication, dose and route of administration. The three most common reference
      sources used in the studies were summary of product characteristics, national
      formularies and package inserts. Overall, the off-label prescribing rates in
      children ranged from 1.2 to 99.7%. The most common category of off-label
      prescribing in children was dose and age. CONCLUSIONS: This review highlighted
      that off-label prescribing in children was found to be highly prevalent
      throughout the past two decades, persistently in the neonatal intensive care
      units. This suggests that besides legislative and regulatory initiatives,
      behavioural, knowledge aspects and efforts to integrate evidence into practice
      related to off-label prescribing also need to be evaluated and consolidated as
      part of the concerted efforts to narrow the gaps in prescribing for children.

PMID- 30218419
TI  - Luteinization desynchronized: the devil is in the details.

PMID- 30218421
TI  - Progressive splenomegaly and mild thrombocytosis in beta-thalassaemia trait and
      coexisting hereditary hemochromatosis: possible confounders for a subsequent
      hematological diagnosis.

PMID- 30218420
TI  - Central Orexin A Affects Reproductive Axis by Modulation of Hypothalamic
      Kisspeptin/Neurokinin B/Dynorphin Secreting Neurons in the Male Wistar Rats.
AB  - It is an established fact that orexin plays an important role in regulating the
      reproductive axis and the secretions of gonadotropin-releasing hormone
      (GnRH)/luteinizing hormone (LH). However, its precise cellular and molecular
      mechanisms are not fully recognized. Accordingly, the aim of the present study is
      to find out whether the central injection of orexin A (OXA) and its antagonists,
      SB-334867 (as orexin receptor antagonist 1; OX1RA) and JNJ-10397049 (as orexin
      receptor antagonist 2; OX2RA), either alone or in combination, can leave any
      impact on the reproductive axis (either hormonal or behavioral) in the male
      Wistar rats. Furthermore, in order to see whether OXA signals can be relayed
      through the pathway of kisspeptin/neurokinin B/dynorphin (known as KNDy neurons,
      a neural network which works upstream of GnRH neurons) or not, the relative gene
      expression of these neuropeptides were measured. Overall, the data from
      radioimmunoassay revealed that OXA significantly decreases the mean serum level
      of LH and testosterone and, in a similar vein, its antagonists neutralize this
      impact. Moreover, data from real-time quantitative PCR indicated that OXA has
      significantly reduced the hypothalamic expression of Gnrh. In this line, the gene
      expressions of Kisspeptin and Neurokinin b decreased. However, OXA antagonists
      neutralize this impact. Also, the expression of Dynorphin gene was upregulated by
      the following application of the OXA. The results of this study are related to
      the impact of orexin on the reproductive axis. It is recommended that KNDy
      neurons as the interneural pathway relay the information of orexin to the GnRH
      neurons.

PMID- 30218422
TI  - Correction to: Implication of OPRM1 A118G Polymorphism in Opioids Addicts in
      Pakistan: In vitro and In silico Analysis.
AB  - The original version of this article is missing the Acknowledgments section.

PMID- 30218424
TI  - Trends of Co-Morbid Depression in Hospitalized Patients with Failed Back Surgery
      Syndrome: An Analysis of the Nationwide Inpatient Sample.
AB  - INTRODUCTION: Co-morbid depression has been associated with poor outcomes
      following spine surgery and worsening of low back pain symptoms leading to failed
      back surgery syndrome (FBSS). Given the increasing focus of healthcare
      utilization and value-based care, it is essential to understand the demographic
      and economic data surrounding co-morbid depression amongst patients with FBSS.
      METHODS: Our study investigated the NIS database for FBSS patients who had co
      morbid depression (ICD-9 CM codes 300.4, 301.12, 309.0, 309.1, 311; ICD-10 M96.1)
      between 2011 and 2015 across 44 states. We obtained demographic and economic data
      such as age, sex, ethnicity, location, number of in-patient procedures, hospital
      length of stay, cost of hospital stay, and frequency of routine discharge
      dispositions. The NIS database represents approximately a 20% sample of
      discharges from hospitals in the United States. These data are weighted to
      provide national estimates for the total United States population. National
      administrative databases (NADs) like National Inpatient Sample (NIS) are a common
      source of data for spine procedures. This database is appealing to investigators
      because of ease of data access and large patient sample. The NIS database is a de
      identified database that consists of a collection of billing and diagnostic codes
      used by participating hospitals with the goal of quality control, population
      monitoring, and tracking procedures. The NIS does not require institutional
      review board (IRB) approval or exempt determination. RESULTS: Between 2011 and
      2015, a total number of 115,976 patients with FBSS were identified. Of these
      patients, about 23,425 had co-morbid depression. The rate of co-morbid depression
      in 2015 was 23% with the lowest reported rate being 20% in 2011. Females and
      Caucasians had consistently higher rates of co-morbid depression compared to
      males and other ethnic groups respectively. The average length of stay for
      patients with co-morbid depression fluctuated between 2011 and 2015, with the
      highest reported at 4.81 days in 2015. The number of procedures increased
      steadily from 2011 to 2015 with a dip in 2013. The highest number of procedures
      was reported as 3.94 in 2015. The mean total hospital charges remained stable
      over time with the largest change being the decrease from 2011 (mean $93,939; 95%
      CI $80,064-$107,815) to 2012 (mean 82,603; 95% CI $75,127-$90,079). Additionally,
      patients with FBSS and co-morbid depression were more often discharged home than
      home with healthcare or to another healthcare facility. CONCLUSIONS: The
      occurrence of co-morbid depression in hospitalized patients with FBSS increased
      from 20% in 2011 to 23% in 2015. While direct hospital costs and length of stay
      remained relatively stable, the number of inpatient procedures performed trended
      upwards. The exact etiology for this increase in depression prevalence is
      unknown; additional studies are needed to shed further insight.

PMID- 30218423
TI  - Carob (Ceratonia siliqua L.) Prevents Short-Term Memory Deficit Induced by
      Chronic Stress in Rats.
AB  - Long-term exposure to stressful conditions could impair the normal brain
      structure and function, specifically the hippocampus-dependent memory. This
      impairment could be attributed to a decrease in brain-derived neurotrophic factor
      (BDNF) levels during chronic stress. Knowing that carob [Ceratonia siliqua L.
      (Fabaceae)] is rich in a wide variety of polyphenols with a high antioxidant
      value, we hypothesized that the methanolic carob extract (C. siliqua) pods will
      prevent stress-induced memory impairment. Hence, the methanolic extract of carob
      pods was investigated for its ability to enhance learning and memory as well as
      to protect from memory impairment in normal stressed animals. Rats were
      chronically stressed for 7 weeks via the intruder stress model. Carob extract was
      administered to animals via intraperitoneal (i.p.) route at a daily dose of 50
      mg/kg. Radial arm water maze (RAWM) was utilized to test for spatial learning and
      memory. In addition, brain tissues were dissected to determine BDNF levels.
      Chronic stress (CS) impaired short-term spatial memory (number of committed
      errors: P < 0.05, days to criterion (DTC): P < 0.001). Animal treatment with
      carob pod extract prevented the short-term memory impairment induced by CS (P <
      0.05), while such treatment showed no effect on memory functions of unstressed
      rats. Moreover, carob pod extract prevented the reduction in the hippocampal BDNF
      (P < 0.05) induced by chronic stress exposure. In conclusion, CS impaired short
      term memory function, while methanolic extract of carob pods prevented this
      impairment, probably as a result of preventing reduction in BDNF levels in the
      hippocampus.

PMID- 30218425
TI  - Value of a Hypothetical Pharmacogenomic Test for the Diagnosis of Statin-Induced
      Myopathy in Patients at High Cardiovascular Risk.
AB  - We recently conducted two economic evaluations of a hypothetical pharmacogenomic
      test for statin-induced myopathy (SIM) in patients at high cardiovascular risk.
      Although the models differed in modeling technique and data inputs, both yielded
      similar results. We believe our approach to assessing the economic value of a
      diagnostic test was highly advantageous as it characterized the complete range of
      false-negative and false-positive test outcomes. We used a broad interpretation
      of test parameters that reflected physician and patient behavioral responses to
      the test results and accounted for patient adherence to treatment. Both economic
      evaluations indicated that a highly accurate pharmacogenomic test for SIM would
      provide a positive incremental net monetary benefit (INMB) for a provincial payer
      in Canada. However, the value of the test would depend on its ability to
      accurately diagnose patients when they experience musculoskeletal pain symptoms
      and guide patients with a test result indicating no SIM to adhere to treatment.
      Interestingly, our results indicated that a highly inaccurate test would still
      yield a positive INMB. We found this surprising result was driven by the
      imbalance of the risk of cardiovascular events outweighing the risk of
      rhabdomyolysis in patients at high cardiovascular risk. A highly accurate
      pharmacogenomic test for SIM in patients at high cardiovascular risk would
      provide economic value for payers. However, the economic and clinical value of
      the test would depend on the credibility of the test results and their success in
      influencing patients without SIM to adhere to therapy.

PMID- 30218426
TI  - Passing the "Acid Test": Do Proton Pump Inhibitors Affect the Composition of the
      Microbiome?

PMID- 30218427
TI  - PNPLA3 Gene Polymorphisms in HCV/HIV-Coinfected Individuals.
AB  - BACKGROUND AND AIMS: The patatin-like phospholipase domain-containing 3 (PNPLA3)
      gene has been associated with the development of alcoholic and nonalcoholic
      steatohepatitis. Using a newly developed and validated assay for PNPLA3, we
      explored the prevalence of gene polymorphisms in a cohort of HCV/HIV-coinfected
      individuals to determine whether there was an association with insulin resistance
      or hepatic fibrosis. METHODS: A high-resolution melting point (HRM) assay was
      developed and validated. The assay was used to evaluate samples obtained in the
      context of a clinical trial performed at ACTG sites across the USA in HIV
      infected patients. Clinical features and treatment outcomes were assessed in
      relation to the PNPLA3 genotype. RESULTS: The HRM methodology demonstrated 100%
      concordance with results obtained by Sanger sequencing. Among 241 participants
      tested, 66.0% had the wild-type allele (CC) and the remainder had the aberrant
      PNPLA3 gene polymorphism in the homozygotic (GG) or heterozygotic (CG) form. Race
      and ethnicity were associated with PNPLA3 genotype but fibrosis stage,
      Homeostatic Model Assessment of Insulin Resistance, and HCV treatment outcome
      were not. CONCLUSION: The HRM method is an effective, rapid technique for
      characterizing PNPLA3 genotype. In those with HCV/HIV infection, nearly 40% carry
      gene polymorphisms associated with the development of NASH or ASH. Prospective
      studies should focus on this group to determine whether they represent a subset
      of HIV-infected persons at increased risk of fibrotic progression.

PMID- 30218429
TI  - Perceived Needs of Veterans Transitioning from the Military to Civilian Life.
AB  - Despite existing separation services provided by the military, many transitioning
      to civilian life report continued or even worsening issues, including anger
      outbursts, PTSD, sustained substance use, and strained family relationships.
      Further, only 61% of the 1,906,754 veterans separated since 2002 participate in
      the VA health care system after separation, indicating that at least three
      quarters of a million veterans are not captured by research conducted in VA
      systems. The current study (N = 90) examined the perceived needs of veterans
      transitioning from the military to civilian life, assessed issues that prevent
      these individuals from participating in VA health care upon separation, and
      captured veteran recommendations to improve existing separation services, either
      prior to or after the transition to civilian life. Veterans identified several
      needs, including improved access to care, mental health and substance use
      counseling, and preparedness for adjustment and economical/financial issues.
      Implications for both care and policy are discussed.

PMID- 30218428
TI  - Cyclic Change of Sphincter of Oddi Motility and Its Relationship with Small Bowel
      Migrating Motor Complex in Humans.
AB  - BACKGROUND: Several animal and human studies have reported that sphincter of Oddi
      (SO) motility shows cyclical changes during the fasting state. However, to date,
      the relationship between the SO motility and the migrating motor complex (MMC) of
      the small bowel (SB) remains unclear in humans. AIMS: We observed SO motility
      over a long study period and evaluated its relationship with the MMC of the SB in
      humans using percutaneous long-term manometry. METHODS: Our study included
      patients with hepatolithiasis who required percutaneous transhepatic catheter
      placement and subsequently underwent choledochoscopy and stone removal. Long-term
      percutaneous transhepatic SO manometry was performed after complete stone
      removal. SO and SB motility were simultaneously recorded. RESULTS: SO motility
      showed cyclical phasic changes with periodic high-frequency contractions similar
      to the MMC contractions of the SB. All high-frequency contractions of the SO
      coincided with phase III contractions of the MMC of the SB. The proportions of
      phase III contractions of SO and SB were similar, but the proportions of phase I
      (P = 0.001) and phase II (P = 0.002) contractions were significantly different.
      The mean basal SO pressure was observed to significantly increase in phase III
      compared to phase I (P = 0.001) and phase II (P = 0.001) contractions.
      CONCLUSIONS: SO motility in humans showed cyclical phasic changes closely
      coordinated with the MMC of the SB in a fasting state; however, the proportion of
      phases differed between the SO and the SB. The basal pressure significantly
      increased during physiological high-frequency phase III contractions of the SO.

PMID- 30218430
TI  - An intensive medical care network led to successful living-donor liver
      transplantation in late-onset hepatic failure with disseminated Staphylococcus
      aureus infection.
AB  - Here, we describe a 42-year-old male patient with late-onset hepatic failure
      (LOHF) due to acute-onset autoimmune hepatitis. At first, his response to steroid
      therapy was good, but hepatitis relapsed during steroid pulse therapy.
      Deterioration of liver function caused LOHF, and LOHF has a poor prognosis,
      particularly when it is complicated by infection. Systemic infection by
      Staphylococcus aureus resulted in a skin rash and septic pulmonary embolism, and
      is an absolute contraindication for liver transplantation (LT). In this treatment
      network, hepatologists and a transplant surgeon cooperated to overcome severe
      infection and their efforts led to successful transplantation. On-line
      hemodiafiltration is an indispensable treatment option for acute liver failure.
      Infection control is crucial for LT and an intensive medical care network led to
      successful living-donor LT.

PMID- 30218431
TI  - Characteristics and Response to Crizotinib in ALK-Rearranged, Advanced Non
      Adenocarcinoma, Non-Small Cell Lung Cancer (NA-NSCLC) Patients: a Retrospective
      Study and Literature Review.
AB  - BACKGROUND: Oncogenic fusion genes consisting of echinoderm microtubule
      associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) can be
      detected in 5-7% of lung adenocarcinoma cases. The prevalence of ALK
      rearrangement in non-adenocarcinoma, non-small cell lung cancers (NA-NSCLC) is
      currently unknown. In addition, the efficacy of crizotinib in these patients has
      not been well established. OBJECTIVES: The aim of this study was to investigate
      the prevalence of ALK rearrangement in NA-NSCLC patients and the therapeutic
      efficacy of crizotinib in these patients. METHODS: We included NA-NSCLC patients
      who were tested for the presence of ALK rearrangement in our institution from
      January 2013 to May 2018. The effectiveness of crizotinib in ALK-positive
      patients was retrospectively analyzed. A literature review was performed and
      eligible previously published cases were analyzed in combination with our data.
      RESULTS: A total of 4662 patients were screened and 1696 NA-NSCLC patients were
      tested for the presence of ALK rearrangement during the study period. Thirty-two
      positive patients were identified (1.9%, 95% CI, 1.2-2.5%). A statistically
      higher percentage of younger (58.0 vs. 63.0, p = 0.01), female patients (53.1%
      vs. 10.8%, p < 0.01) who were non-smokers (71.9% vs. 40.6%, p < 0.01) and whose
      tumors contained adenocarcinoma components (34.4% vs. 6.1%, p < 0.01) were
      observed in the ALK-positive group. Eighteen patients were excluded from the
      study and 14 eligible patients were included for survival analysis. The median
      duration of crizotinib treatment (MDT) as a proxy for progression-free survival
      of the 14 eligible patients in our institution was 6.0 months (95% CI, 1.2-10.8
      months). We combined our data with sporadic cases from 16 previous publications
      (total n = 37) and found that the MDT was 7.0 months (95% CI, 6.0-8.0 months).
      CONCLUSIONS: Our study suggests the opportunity to test ALK rearrangement in NA
      NSCLC patients, especially in younger, female, non-smoking patients containing
      adenocarcinoma components. Crizotinib provides an option for the treatment of NA
      NSCLC patients who have an ALK rearrangement.

PMID- 30218432
TI  - Improved Treatment Engagement Among Patients with Diabetes Treated with Insulin
      Glargine 300 U/mL Who Participated in the COACH Support Program.
AB  - INTRODUCTION: Persistence with basal insulin therapy can be suboptimal, despite
      recent improvements in insulin formulations and delivery systems. Patient support
      programs may help increase adherence. This study evaluated the impact of the
      Toujeo(r) COACH support program, which provides patients with continuing and
      individualized education and advice on lifestyle changes, by assessing its effect
      on number of refills and days on therapy. METHODS: The study population included
      1724 patients with diabetes who filled a first prescription for insulin glargine
      300 U/mL (Gla-300) between April and December 2015 and received a welcome call
      from a Guide, and 1724 matched control patients from the Symphony Health
      Integrated Dataverse(r) prescription claims database. Control patients received
      Gla-300 but did not enroll in the program. These patients were matched based on
      age, gender, location, prior use of insulin, insulin dose, number of concomitant
      drugs, and copay tier. RESULTS: The COACH and control groups comprised 52% men
      and 48% women; 22% were aged 18-47 years, 23% were 48-55 years, 27% 56-61 years,
      and 28% >= 62 years. Most (99%) had used insulin in the year before receiving the
      welcome call. At 6 months, patients in the COACH group had refilled their
      prescription 3.2 times on average, compared with 2.4 times for control patients
      (P < 0.0001); at 9 months, the average number of refills was 4.7 and 3.6,
      respectively (P < 0.0001). The average number of days on therapy at 6 months was
      102.2 days in the COACH group and 81.5 days in the control group (P < 0.0001); at
      9 months, the average number of days on therapy was 151.9 and 121.6, respectively
      (P < 0.0001). CONCLUSION: Patients in the COACH program were significantly more
      likely to refill their prescriptions and stay on therapy. Patient support
      programs such as the COACH program could be an effective way to help improve
      diabetes care. FUNDING: Sanofi US, Inc. and McKesson Corporation.

PMID- 30218433
TI  - Diabetes and Diet: A Patient and Dietitian's Perspective.
AB  - This article has been co-authored by a patient with type 2 diabetes and a
      specialist dietitian. Here they discuss the patient's experience and difficulties
      with controlling weight and strategies that can help a patient in this situation.
      The patient discusses how stress and her corresponding comfort eating dampened
      weight loss progress, and how adopting a lifestyle change aided through group
      support helped to deal with this. The physician discusses the importance of
      recognizing the mental and physical challenges faced by patients in this
      situation.

PMID- 30218434
TI  - Bedtime-to-Morning Glucose Difference and iGlarLixi in Type 2 Diabetes: Post Hoc
      Analysis of LixiLan-L.
AB  - INTRODUCTION: A difference of >= 50-55 mg/dL between bedtime and morning glucose
      (BeAM) values in patients with type 2 diabetes (T2D) on basal insulin is an
      indicator of poor postprandial glucose control. This analysis compared the effect
      of treatment with a fixed-ratio combination of insulin glargine/lixisenatide
      (iGlarLixi) vs insulin glargine (iGlar) on BeAM values, and evaluated the impact
      of BeAM values on glycemic and safety endpoints. METHODS: In this post hoc
      analysis of 517 participants from the LixiLan-L trial, change in BeAM values and
      composite efficacy and safety endpoints stratified by BeAM value < 55 mg/dL or >=
      55 mg/dL were evaluated in patients with T2D uncontrolled on basal insulin
      randomized to iGlarLixi or iGlar over 30 weeks (LixiLan-L). RESULTS: Greater
      reductions in BeAM values were seen with iGlarLixi vs iGlar, and a higher
      proportion of patients reached a BeAM value < 55 mg/dL in the iGlarLixi arm. A
      BeAM value < 55 mg/dL was associated with improved glycemic control, lower risk
      of hypoglycemia, and a greater proportion of patients achieving glycemic targets
      without hypoglycemia or weight gain. Greater reductions in BeAM values were seen
      with iGlarLixi vs iGlar, irrespective of stratification by glycated hemoglobin
      A1c or glycemic endpoints. CONCLUSIONS: Greater reductions in bedtime-to-morning
      glucose differential, or BeAM, were observed with iGlarLixi vs iGlar in patients
      with T2D uncontrolled on basal insulin, reflecting better overall control of both
      fasting and prandial glucose and more appropriate matching of therapy to
      physiologic needs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02058160.
      FUNDING: Sanofi US, Inc.

PMID- 30218435
TI  - Correction to: A Comparison of Measurements of a Pediatric Supplement.
AB  - The original version of this article unfortunately contained mistakes.

PMID- 30218436
TI  - Heart failure with recovered ejection fraction.
AB  - Substantial or complete myocardial recovery occurs in many patients with heart
      failure (HF). HF patients with myocardial recovery or recovered left ventricular
      (LV) ejection fraction (EF; HFrecEF) are a distinct population of HF patients
      with different underlying etiologies, comorbidities, response to therapies, and
      outcomes compared with HF patients with persistent reduced or preserved EF.
      Improvement in LVEF has been systematically linked to improved quality of life,
      and lower rehospitalization rates and mortality. However, the mortality and
      morbidity in HFrecEF patients remain higher than those in the normal population.
      Currently, data to guide the management of HFrecEF patients are lacking. This
      review discusses specific characteristics, pathophysiology, and clinical
      implications for HFrecEF.

PMID- 30218437
TI  - Associations of 26 Circulating Inflammatory and Renal Biomarkers with Near
      Infrared Spectroscopy and Long-term Cardiovascular Outcome in Patients Undergoing
      Coronary Angiography (ATHEROREMO-NIRS Substudy).
AB  - PURPOSE OF REVIEW: The purpose of this study was to investigate the association
      of 26 inflammatory biomarkers (acute phase proteins, cytokines, chemokines) and
      renal markers with coronary lipid core burden index (LCBI) assessed by near
      infrared spectroscopy (NIRS) imaging, as well as the association of these
      biomarkers with long-term cardiovascular outcome. RECENT FINDINGS: NIRS-derived
      LCBI has recently been shown to be an independent predictor of major adverse
      cardiac events (MACE). However, studies on the association between circulating
      biomarkers and NIRS-derived characteristics have not yet been performed. Between
      2008 and 2011, 581 patients underwent diagnostic coronary angiography or
      percutaneous coronary intervention for stable angina pectoris or acute coronary
      syndrome (ACS). NIRS of a non-culprit vessel was performed in a subset of 203
      patients. In multivariable analyses, TNF-alpha tended to be associated with
      higher LCBI (beta 0.088 ln (pg/ml) increase per unit LCBI; 95% CI 0.000-0.177, p
      = 0.05) after adjustment for clinical characteristics. However, this association
      did not persist after Bonferroni correction (statistical threshold 0.0019). Major
      adverse cardiac events (MACE) were registered in 581 patients during a median
      follow-up time of 4.7 years (IQR: [4.2-5.6] years). After adjustment for clinical
      characteristics and Bonferroni correction, IL-8 (HR 1.60; 95% CI [1.18-2.17] per
      ln (pg/ml), p = 0.002) was borderline associated with MACE and significantly
      associated with all-cause mortality or ACS (HR 1.75; 95% CI [1.24-2.48] per ln
      (pg/ml), p = 0.0015). In conclusion, we found that IL-8 was independently
      associated with clinical outcome, but altogether, the multiplex panel we
      investigated here did not render a useful blood biomarker of high LCBI.

PMID- 30218438
TI  - The Walking Wounded: Emerging Treatments for PTSD.
AB  - PURPOSE OF REVIEW: We review the published literature over the last 24 months in
      the treatment of PTSD for our military men and women. We examined the updated
      clinical practice guidelines published in June 2017 by the Veteran's
      administration and Department of Defense and contrasted the guidelines with the
      most recent literature. We also discuss new directions in PTSD research. RECENT
      FINDINGS: Psychotherapy remains one of the most effective treatments for PTSD;
      unfortunately, few participants remain in treatment to completion. Many of the
      emerging therapies target NMDA receptor antagonists, cannabinoid receptor
      modulators, glucocorticoid receptor agonists, non-SSRI antidepressants, and
      opioid receptor agonists. The newer therapies fall into the drug classes of anti
      hypertensives, glutamate modulators, oxytocin, and medication targeting
      insomnia/hyperarousal. PTSD symptoms are often chronic in our veteran population.
      While current treatments are helpful, there are often significant residual
      symptoms. We reviewed the most recent improvements in treatment and discuss
      therapies that are in the research phase.

PMID- 30218439
TI  - Offering HeLP to work out the optimum treatment for haemorrhoidal disease.

PMID- 30218441
TI  - Selected Abstracts from XXXV National Congress of the Italian Society of
      Hypertension (SIIA), Rome, 27-29 September 2018.

PMID- 30218440
TI  - The association of sleep-disordered breathing and white matter hyperintensities
      in heart failure patients.
AB  - Heart failure patients often manifest white matter hyperintensites on brain
      magnetic resonance imaging (MRI). White matter hyperintnsities have also been
      linked with cognitive problems in patients with heart failure. Sleep disordered
      breathing may contribute to structural brain changes in heart failure. The
      purpose of this study was to test the extent to which the apnea hypopnea index is
      associated with global and regional white matter hyperintensities, and is a
      moderating factor in the relationship between age and white matter
      hyperintensites. A total of 28 HF patients [mean age (SD) = 67.89 (5.8)]
      underwent T1-weighted and T2FLAIR MRI and a home sleep monitoring study. The
      apnea hypopnea index cut off of 10 was used to compare between higher and lower
      risks of sleep disordered breathing. Regression analysis was used to test the
      association between apnea hypopnea index and both global and regional white
      matter hyperintensities. The interaction term was entered to identify the
      moderation effect. Apnea hypopnea index was associated with higher regional white
      matter hyperintensities but not global white matter hyperintensities. There was a
      significant interaction between the apnea hypopnea index and age, such that older
      participants with the apnea hypopnea index >=10 showed greater regional white
      matter hyperintensities than those with the apnea hypopnea index <10. The results
      of this preliminary study indicate that a higher apnea hypopnea index is
      associated with more white matter hyperintensities. The age-related white matter
      hyperintensities appear to be exacerbated by apnea hypopnea index in our
      individuals with heart failure. Future studies are needed to further investigate
      the underlying mechanisms.

PMID- 30218442
TI  - Increased tacrolimus blood concentration by Beni-Madonna - a new hybrid citrus
      cultivar categorized as 'Tangor', in a liver transplant patient: likely
      furanocoumarin-mediated inhibition of CYP3A4 or P-glycoprotein.
AB  - ADVERSE EVENT: A drug interaction leading to greater exposure to tacrolimus. DRUG
      IMPLICATED: Tacrolimus and Beni-Madonna (a new cultivar citrus categorized as
      'Tangor'). THE PATIENT: A 9-month-old girl with biliary atresia (body weight, 7.5
      kg) taking tacrolimus after liver transplantation. EVIDENCE THAT LINKS THE DRUG
      TO THE EVENT: The time course was consistent with the appearance of the
      interaction, which was confirmed by an increase in the blood concentration of
      tacrolimus. Dihydroxybergamottin was detected in peel of Beni-Madonna and in peel
      and fruit pulp of grapefruit. MANAGEMENT: Avoiding Beni-Madonna intake.
      MECHANISM: Inhibition of activity of CYP3A4, P-glycoprotein, or both, by Beni
      Madonna. IMPLICATION FOR THERAPY: Clinicians should be aware of this potential
      interaction, and patients taking drugs such as tacrolimus (the kinetics of which
      are affected by grapefruit juice) should avoid Beni-Madonna intake. HYPOTHESIS TO
      BE TESTED: Further study is required to determine if other Citrus species
      categorized as Tangor contain furanocoumarins.

PMID- 30218443
TI  - Evaluation of the ability of colistin, amoxicillin (components of Potencil(r) ),
      and fluoroquinolones to attenuate bacterial endotoxin- and Shiga exotoxin
      mediated cytotoxicity-In vitro studies.
AB  - Escherichia coli is one of the major pathogens in humans and animals causing
      localized and systemic infections, which often lead to acute inflammation, watery
      diarrhea, and hemorrhagic colitis. Bacterial lipopolysaccharide (LPS) and Shiga
      exotoxins (Stx) are mostly responsible for such clinical signs. Therefore, highly
      effective treatment of E. coli infections should include both eradication of
      bacteria and neutralization of their toxins. Here, for the first time, we
      compared the in vitro ability of common antibiotics to decrease LPS- and Stx
      mediated cytotoxicity: colistin, amoxicillin (used separately or combined),
      enrofloxacin, and its metabolite ciprofloxacin. Three experimental scenarios were
      realized as follows: (a) the direct effect of antibiotics on endotoxin, (b) the
      effect of antibiotic treatment on LPS-mediated cytotoxicity in an experiment
      mimicking "natural infection," (c) the effect of antibiotics to decrease Stx2e
      mediated cytotoxicity. Two cell lines, A549 and Vero cells, were used to perform
      cytotoxic assays with the methyl tetrazolium (MTT) and lactate dehydrogenase
      leakage (LDH) methods, respectively. Colistin and amoxicillin, especially used in
      combination, were able to attenuate LPS toxic effect, which was reflected by
      increase in A549 cell viability. In comparison with other antibiotics, the
      combination of colistin and amoxicillin exhibited the highest boster or additive
      effect in protecting cells against LPS- and Stx2e-induced toxicity. In summary,
      in comparison with fluoroquinolones, the combination of colistin and amoxicillin
      at concentrations similar to those achieved in plasma of treated animals
      exhibited the highest ability to attenuate LPS- and Stx2e-mediated cytotoxicity.

PMID- 30218444
TI  - Allogeneic stem cell transplantation following relapse post autologous stem cell
      transplantation in adult patients with acute myeloid leukemia: A retrospective
      analysis of 537 patients from the Acute Leukemia Working Party of the EBMT.
AB  - Patients with acute myeloid leukemia (AML) who relapse after autologous stem cell
      transplantation (ASCT) can be rescued by allogeneic SCT. We identified 537 adult
      patients with AML allografted in second complete remission (CR2) or first relapse
      after ASCT in the European Society for Blood and Marrow Transplantation (EBMT)
      registry. At 3 years post allograft, leukemia free survival (LFS) was 31.4%
      [95%CI 27.3-35.6], overall survival (OS) 39.5% [95%CI 35.1-43.9], relapse
      incidence (RI) 34.6% [95%CI 30.4-38.8], and nonrelapse mortality (NRM) 33.7%
      [95%CI 29.6-37.9]. RI was higher in patients transplanted in relapse in
      comparison to those transplanted in CR2 (HR 1.76, P = .004) and in patients who
      relapsed later after ASCT (HR 0.97 per month, P < 10-3 ), both translating into
      better LFS/ OS. Relapse was also lower in patients undergoing allogeneic stem
      cell transplantation (allo-HSCT) from an unrelated donor (UD) in comparison to
      those transplanted from a matched sibling donor (MSD) (HR 0.49, P < 10-3 ). NRM
      was increased in patients who received total body irradiation (TBI) pre-ASCT (HR
      2.43; P < 10-4), translating into worse LFS/OS. LFS/OS did not differ between
      patients allotransplanted with reduced intensity (RIC) or myeloablative (MAC)
      conditioning. In conclusion, one third of adult patients with AML relapsing post
      ASCT can be rescued with allo-HSCT, with better LFS/OS in patients who relapsed
      later post ASCT, those transplanted in CR2 and those who had not received TBI pre
      ASCT.

PMID- 30218446
TI  - Phosphoinositide-dependent kinase 1-associated glycolysis is regulated by miR-409
      3p in clear cell renal cell carcinoma.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most popular kidney cancer in
      adults. Metabolic shift toward aerobic glycolysis is a fundamental factor for
      ccRCC therapy. MicroRNAs (miRNAs) are thought to be important regulators in ccRCC
      development and progression. Phosphoinositide-dependent kinase 1 (PDK1) is
      required for metabolic activation; however, the role of PDK1-induced glycolytic
      metabolism regulated by miRNAs is unclear in ccRCC. So, the purpose of the
      current study is to elucidate the underlying mechanism in ccRCC cell metabolism
      mediated by PDK1. Our results revealed that miR-409-3p inhibited glycolysis by
      regulating PDK1 expression in ccRCC cells. We also found that miR-409-3p was
      regulated by hypoxia. Our results indicated that PDK1 facilitated ccRCC cell
      glycolysis, regulated by miR-409-3p in hypoxia.

PMID- 30218445
TI  - Clozapine as a first- or second-line treatment in schizophrenia: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: No consensus exists on whether clozapine should be prescribed in early
      stages of psychosis. This systematic review and meta-analysis therefore focus on
      the use of clozapine as first-line or second-line treatment in non-treatment
      resistant patients. METHODS: Articles were eligible if they investigated
      clozapine compared to another antipsychotic as a first- or second-line treatment
      in non-treatment-resistant schizophrenia spectrum disorders (SCZ) patients and
      provided data on treatment response. We performed random-effects meta-analyses.
      RESULTS: Fifteen articles were eligible for the systematic review (N = 314
      subjects on clozapine and N = 800 on other antipsychotics). Our meta-analysis
      comparing clozapine to a miscellaneous group of antipsychotics revealed a
      significant benefit of clozapine (Hedges' g = 0.220, P = 0.026, 95% CI = 0.026
      0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis
      revealed a significant benefit of clozapine over risperidone (Hedges' g = 0.274,
      P = 0.030, 95% CI = 0.027-0.521). CONCLUSION: The few eligible trials on this
      topic suggest that clozapine may be more effective than other antipsychotics when
      used as first- or second-line treatment. Only large clinical trials may
      comprehensively probe disease stage-dependent superiority of clozapine and
      investigate overall tolerability.

PMID- 30218447
TI  - Demographic Composition of Select Oncologic New Molecular Entities Approved by
      the FDA Between 2008 and 2017.
AB  - Race, ethnicity, sex, and age are demographic factors that can influence drug
      exposure and/or response, and can consequently affect treatment outcome. We
      evaluated demographic subgroup enrollment patterns in new therapeutic products
      approved by the US Food and Drug Administration (FDA) for the treatment of select
      cancers-breast, colorectal, lung, and prostate-that have comparative differences
      in morbidity and/or mortality among some demographic subgroups. In submissions of
      products approved between 2008 and 2013, participants (n = 22,481) were white
      (80%), from outside the United States (74%), between 17 and 64 years old (59%),
      and men (56% and 53%, including and excluding sex-specific indications,
      respectively). In pivotal trials of products approved between2014 and 2017,
      participants (n = 3,612) were white (71%), between 17 and 64 years old (61%), and
      men (48% and 63%, including and excluding sex-specific indications,
      respectively). The US-relevant minority populations were under-represented. A
      broader representation of patient subgroups in clinical trials may contribute to
      better understanding of exposure and/or response variability, and consequently
      help personalize drug therapy.

PMID- 30218448
TI  - Chronic alcohol consumption increases inflammation and osteoclastogenesis in
      apical periodontitis.
AB  - AIM: To investigate the effect of chronic alcohol consumption on apical
      periodontitis in rats. METHODOLOGY: Thirty-two male Wistar rats were arranged
      into four groups: Control (C): without apical periodontitis and nonalcoholic
      diet; (AL): without apical periodontitis and alcoholic diet; (AP): with apical
      periodontitis and nonalcoholic diet; and (AP + AL): with apical periodontitis and
      alcoholic diet. The alcoholic solution at 20% was given to the AL and AP + AL
      groups as the sole source of hydration throughout the experiment. AP was induced
      in the mandibular left first molars at the end of the 4th week. Weight changes
      and the amount of solid and liquid foods were recorded for 8 weeks. At the end,
      the animals were euthanized and the jaws removed followed by histological
      processing for histopathological and RANKL, OPG, TRAP and HIF-1alpha analyses.
      The Mann-Whitney test was used for nonparametric data, and anova followed by the
      Tukey test was performed for parametric data, with P < 0.05. RESULTS: Animals
      that received the alcoholic diet had a lower weight gain than the other groups (P
      < 0.05). Control and AL groups did not have an inflammatory response in the
      periapical tissues. The median score of inflammatory infiltrate was significantly
      higher in the AP + AL group (2.5) compared to the AP group (1.5; P < 0.05). In
      the same comparison, AP + AL was associated with score 3 for RANKL and HIF-1alpha
      versus score 2 for AP group (P < 0.05). Moreover, the values for TRAP were 3.88
      +/- 0.70 cells mm-1 for the AP + AL group and 2.43 +/- 0.94 cells mm-1 for the AP
      group (P < 0.05). CONCLUSION: In rats, an alcoholic diet had a significant effect
      on the severity of apical periodontitis, exacerbating the inflammatory response
      and osteoclastogenesis.

PMID- 30218449
TI  - 18 F-sodium fluoride positron emission tomography of the racing Thoroughbred
      fetlock: Validation and comparison with other imaging modalities in nine horses.
AB  - BACKGROUND: Early and accurate detection of stress remodelling in racehorses is
      of utmost importance to prevent catastrophic injuries. Current imaging techniques
      have limitations in assessing early changes predisposing to catastrophic
      breakdowns. Positron emission tomography (PET) using 18 F-sodium fluoride (18 F
      NaF) is a sensitive method for the detection of early bone turnover and may
      improve early recognition of subtle injuries. OBJECTIVES: To validate the
      clinical use of 18 F-NaF PET in Thoroughbred racehorses, to assess the value of
      PET in the detection of bone lesions and to compare PET results with findings of
      other advanced imaging modalities, clinical examination and pathology. STUDY
      DESIGN: Experimental exploratory study. METHODS: Twenty fetlocks from nine
      Thoroughbred racehorses were imaged using 18 F-NaF PET, computed tomography (CT)
      and scintigraphy. Five fetlocks were also imaged with magnetic resonance imaging
      and four fetlocks were also examined histologically. Imaging findings were
      independently reviewed by three board certified radiologists. Imaging, clinical
      and histopathological findings were correlated. RESULTS: PET imaging was well
      tolerated by all horses. PET detected focal areas of 18 F-NaF uptake in instances
      where other imaging modalities did not identify abnormalities, in particular in
      the proximal sesamoid bones. Maximal standardised uptake values could be measured
      to quantify the activity of lesions. Areas of 18 F-NaF uptake corresponded to
      regions of increased vascularity and increased osteoblastic activity. MAIN
      LIMITATIONS: Limited number of cases. CONCLUSIONS: 18 F-NaF PET imaging of the
      Thoroughbred fetlock is feasible and compares favourably with other imaging
      modalities in detecting stress remodelling in Thoroughbred racehorses. PET
      appears to be a beneficial imaging modality when used for early detection of
      stress remodelling in an effort to prevent catastrophic musculoskeletal injuries
      in this population of horses.

PMID- 30218450
TI  - Favorable effect of mycorrhizae on biomass production efficiency exceeds their
      carbon cost in a fertilization experiment.
AB  - Biomass production efficiency (BPE), the ratio of biomass production to
      photosynthesis, varies greatly among ecosystems and typically increases with
      increasing nutrient availability. Reduced carbon partitioning to mycorrhizal
      fungi (i.e., per unit photosynthesis) is the hypothesized underlying mechanism,
      as mycorrhizal abundance and plant dependence on these symbionts typically
      decrease with increasing nutrient availability. In a mesocosm experiment with Zea
      mays, we investigated the effect of nitrogen (N) and phosphorus (P) addition and
      of mycorrhizal inoculation on BPE. Photosynthesis and respiration were measured
      at mesocosm scale and at leaf scale. The growth of arbuscular mycorrhizal fungi
      (AMF) was assessed with ingrowth bags while also making use of the difference in
      delta13 C between C4 plants and C3 soil. Mesocosms without AMF, that is, with
      pasteurized soil, were used to further explore the role of AMF. Plant growth,
      photosynthesis, and BPE were positively affected by P, but not by N addition. AMF
      biomass also was slightly higher under P addition, but carbon partitioning to AMF
      was significantly lower than without P addition. Interestingly, in the absence of
      AMF, plants that did not receive P died prematurely. Our study confirmed the
      hypothesis that BPE increases with increasing nutrient availability, and that
      carbon partitioning to AMF plays a key role in this nutrient effect. The
      comparison of inoculated vs. pasteurized mesocosms further suggested a lower
      carbon cost of nutrient uptake via AMF than via other mechanisms under nutrient
      rich conditions.

PMID- 30218451
TI  - Nitric oxide inhibits hypoxia-induced impairment of human RBC deformability
      through reducing the cross-linking of membrane protein band 3.
AB  - AIM: Nitric oxide (NO) prevents the decline of RBC deformability under high
      altitude and other ischemic and hypoxic conditions, but the clear mechanisms
      remain unknown. Here, we have carried out a systematic study to find the
      mechanisms of NO-induced regulation of RBC deformability under hypoxia. METHODS:
      NO levels, RBCs membrane elongation index (EI), membrane protein band 3
      methemoglobin (MetHb) were determined during hypoxia (0 to 120 minutes). To
      validate the role of NO in regulating RBC deformability, tests were also
      performed with a NO donor (sodium nitroprusside) or a NO synthase inhibitor (l
      nitro-arginine methylester) under 60 minutes hypoxia. RESULTS: Hypoxia for 45
      minutes increased NO levels from 25.65 +/- 1.95 to 35.26 +/- 2.01 MUmol/L, and
      there was a plateau after 60 minutes hypoxia. The EI did not change before 45
      minutes hypoxia, but decreased from 0.567 +/- 0.019 to 0.409 +/- 0.042 (30 Pa)
      after 60 minutes hypoxia. The cross-linking of band 3 and phosphotyrosine
      increased after 45 minutes hypoxia. All can be alleviated by supplement NO and
      aggregated by inhibiting NOS. However, the MetHb was not present this trend.
      CONCLUSION: NO may prevent decreased of RBCs deformability through reducing the
      cross-linking of membrane band 3 under hypoxia; this helps microvascular
      perfusion of RBCs during ischemic and hypoxic disease states.

PMID- 30218452
TI  - Matrix stiffness mediates stemness characteristics via activating the Yes
      associated protein in colorectal cancer cells.
AB  - Matrix stiffness is an essential physical microenvironment in solid cancer.
      However, its influence on cancer stemness still remains elusive. Colorectal
      cancer (CRC) cell line HCT-116 was cultured in the matrix with various stiffness.
      The siYAP was applied to detect the changes of stemness markers. The cancer
      stemness markers, Yes-associated protein (YAP), Lamin A/C and downstream protein
      molecules, and their activation were measured after the treatment with anti-beta1
      integrin and FAK inhibitors. In CRC tissue samples, collagen deposition and the
      expression of alpha-SMA and CD133 were detected. The study found that the
      expression level of stemness markers and Lamin A/C increased as the matrix
      stiffness raised and was regulated by YAP activation in CRC stem cells.
      Inhibition of beta1-integrin and FAK activation in a high stiffness cell culture
      medium significantly decreased the activation of YAP, PI3K, and AKT. Collagen was
      highly deposited in the CRC invasive tumor front (ITF), and the expression of
      CD133 was higher in ITF compared with normal tissue and the tumor cells.
      Moreover, the expression level of alpha-SMA was positively correlated with CD133
      expression level. Together, our results suggest that activation of YAP in CRC
      plays an important role in the promotion of cancer stem cell properties by
      extracellular matrix stiffness in CRC.

PMID- 30218453
TI  - Nomological consistency: A comprehensive test of the equivalence of different
      trait indicators for the same constructs.
AB  - OBJECTIVE: Across all subfields of psychology, it is common practice to use
      different indicators of allegedly the same personality constructs, resting upon
      the (often implicit) assumption that the indicators measure equivalent
      constructs. However, there is a lack of approaches allowing for a strict and
      comprehensive test of the equivalence assumption. We propose investigating
      nomological consistency to test the equivalence assumption across inventories
      allegedly measuring the same set of constructs. Nomological consistency refers to
      the degree to which different indicators of constructs in a theoretical or
      structural model (such as the Big Five) show similar (non-)associations with a
      set of external criteria, thus testing the consistency of the nomological net
      spanned by different indicators. METHOD: In a large-scale study based on a
      convenience sample (N = 2,846; 64.9% female), we provide an empirical
      demonstration of nomological consistency across three commonly used Big Five
      inventories by comparing the pattern of associations of the Big Five constructs
      across inventories with five external criteria using a multifaceted analytic
      approach. RESULTS: Although results showed some level of consistency across the
      Big Five inventories under scrutiny, there was also a relevant extent of
      nomological inconsistency. CONCLUSIONS: Testing nomological consistency allows
      for a more conclusive judgment on the equivalence of different indicators across
      inventories.

PMID- 30218454
TI  - The "American (cancer) patients first" plan to reduce drug prices-A critical
      assessment.

PMID- 30218455
TI  - Prediction of GABARAP interaction with the GABA type A receptor.
AB  - We have performed docking simulations on GABARAP interacting with the GABA type A
      receptor using SwarmDock. We have also used a novel method to study hydration
      sites on the surface of these two proteins; this method identifies regions around
      proteins where desolvation is relatively easy, and these are possible locations
      where proteins can bind each other. There is a high degree of consistency between
      the predictions of these two methods. Moreover, we have also identified binding
      sites on GABARAP for other proteins, and listed possible binding sites for as yet
      unknown proteins on both GABARAP and the GABA type A receptor intracellular
      domain.

PMID- 30218456
TI  - Measuring Intraventricular Pressure Using Ultrasound Elastography.
AB  - OBJECTIVES: Intraventricular pressure (IVP) is one of the most important
      measurements for evaluating cardiac function, but this measurement is not
      currently easily assessable in the clinic. The primary reason for this is the
      absence of a noninvasive technique for measuring IVP. In this study, we
      investigate the relationship between IVP and dynamic myocardial stiffness
      measured by shear wave elasticity imaging (SWEI) and assess the feasibility of
      measuring IVP using SWEI. METHODS: In 8 isolated working rabbit hearts, IVP was
      recorded in the left ventricle using a pressure catheter. Simultaneously,
      myocardial stiffness was recorded by SWEI. Using the peak values for IVP and SWEI
      measured stiffness, SWEI measurements were calibrated and converted to IVP.
      RESULTS: A linear relationship with zero intercept was observed between IVP and
      SWEI, with the average slope of 0.318 kPa/mm Hg, R2  = 0.89. Using one point on
      the IVP/SWEI curve, SWEI measurements were converted to IVP. Estimated pressure
      using SWEI and IVP were linearly correlated with the slope of 0.95, R2  = 0.88
      (mean end diastolic pressure by pressure catheter = 12.716 mm Hg and by
      SWEI=14.726 mm Hg), indicating the near equivalence of the 2 measurements.
      CONCLUSION: We have shown that SWEI measurements are linearly related to IVP;
      therefore, pressure-based indices could potentially be derived from SWEI
      ultrasound elastography. The feasibility of using SWEI to estimate IVP with a
      single point calibration was also shown in this study.

PMID- 30218457
TI  - Sodium selenite induces apoptosis via ROS-mediated NF-kappaB signaling and
      activation of the Bax-caspase-9-caspase-3 axis in 4T1 cells.
AB  - Sodium selenite (SSE), a source of inorganic selenium, has been widely used as a
      clinical cancer treatment, but the precise molecular mechanisms of SSE remain to
      be elucidated. Our in vitro experiments have confirmed that SSE treatment causes
      a transient increase in intracellular reactive oxygen species (ROS) levels,
      resulting in the inhibition of nuclear transcription factor-kappaB (NF-kappaB)
      signaling and p65 and nuclear factor of kappa light polypeptide gene enhancer in
      B-cells inhibitor, alpha phosphorylation levels in 4T1 cells. The inhibition of
      NF-kappaB subsequently increased the expression of the apoptosis gene B-cell
      lymphoma-2-associated X (Bax) and downregulated the transcription of
      antiapoptosis genes, such as B-cell lymphoma-2, cellular inhibitor of apoptosis
      1, and X-linked inhibitor of apoptosis. Additionally, the accumulation of ROS
      caused mitochondrial dysfunction, leading to the activation of caspase-9 and -3,
      thereby resulting in apoptosis. However, modulation of the ROS level by the
      chemical inhibitor N-acetyl-cysteine reversed these events. Similarly, in vitro
      murine syngeneic breast tumor models showed that SSE inhibits tumor growth by
      promoting apoptosis. These results indicate that SSE induces apoptosis via ROS
      mediated inhibition of NF-kappaB signaling and activation of the Bax-caspase-9
      caspase-3 axis.

PMID- 30218458
TI  - Going deeper: three-dimensional study of gammadelta T cells in mouse reproductive
      tract using tissue clearing methods.
AB  - Several tissue clearing methods have been developed for three-dimensional imaging
      of thick specimens. Here, we applied CUBIC and ScaleS approaches to whole-mounted
      vaginal wall to reveal spatial distribution of gammadelta T lymphocytes, the key
      cells engaged in the epithelial homeostasis control and immune surveillance. Both
      methods rendered the tissue transparent and enabled detection of the green
      fluorescent protein (GFP)-expressing gammadelta T cells in vaginal samples of
      Tcrd-H2BeGFP transgenic mice. Upon additional immunolabeling, however, only CUBIC
      preserved the GFP signal and allowed for cell localization assessment during the
      estrous cycle. Using a combination of single- and two-photon microscopy, we found
      that during the diestrus phase the number of gammadelta T cells in the vaginal
      wall increased compared to estrus, while the proportion of cells residing in
      epithelium and stroma remained constant, irrespective of the cycle phase, and was
      close to 3:1, respectively. Moreover, the distance from epithelial gammadelta T
      cells to laminin-positive basal membrane and collagen-rich stroma also increased
      in diestrus in spite of thinning of epithelium upon shedding cornified cells. Our
      data indicate that gammadelta T cells sense sex hormone fluxes which influence
      their number and position them closer to the vaginal lumen in the diestrus phase.

PMID- 30218459
TI  - Determination of milk/plasma ratio and milk and plasma pharmacokinetics of
      amoxicillin after intramuscular administration in lactating cows.
AB  - This study was conducted to determine the passage ratio of amoxicillin into milk
      and its pharmacokinetics in milk and plasma after intramuscular administration.
      Five healthy dairy cows (Holstein, weighing 450-500 kg, aged 2-4 years) were used
      in this study. They received single intramuscular amoxicillin at a dose of 14
      mg/kg body weight. Blood and milk samples were collected prior to drug
      administration (0); after 15, 30, 45, 60, and 90 min; and 2, 3, 4, 6, 8, 10, and
      12 hr after administration. The plasma and milk concentrations of amoxicillin
      were determined using high-performance liquid chromatography with ultraviolet
      detection. The passage ratio of amoxicillin into milk and plasma was determined
      using both AUC-based calculation and milk and plasma concentrations at sampling
      times; it was calculated 0.46 and 0.52, respectively. The terminal half-life and
      mean residence time of amoxicillin were 6.05 and 8.60 hr in plasma and 2.62 and
      5.35 hr in milk, respectively. The Cmax2 levels of amoxicillin in plasma and milk
      were measured as 1,096 and 457 ng/ml, respectively. It was observed that
      amoxicillin exhibited a secondary peak in plasma and milk. This study was the
      first to report on the passage ratio of amoxicillin into milk in lactating cows.

PMID- 30218460
TI  - Appendectomy and risk of Parkinson's disease in two large prospective cohorts of
      men and women.
AB  - BACKGROUND: Prior work on appendectomy and PD has produced mixed results. In this
      study we examined whether history of self-reported appendectomy was related to
      risk of incident Parkinson's disease in the Nurses' Health Study and the Health
      Professionals Follow-up Study. METHODS: We used the Cox proportional hazards
      model to estimate the hazard ratio of Parkinson's disease associated with self
      report of appendectomy in men and women. Among women, we estimated the hazard
      ratio of Parkinson's disease associated with appendectomy for appendicitis and
      incidental appendectomy. RESULTS: In pooled analyses, self-report of any
      appendectomy was not related to Parkinson's disease risk: the hazard ratio of
      Parkinson's disease comparing participants who reported any appendectomy with
      those who did not was 1.08 (95% confidence interval, 0.94-1.23). In women,
      appendectomy for appendicitis, but not incidental appendectomy, was associated
      with a modestly elevated risk of Parkinson's disease (hazard ratio, 1.23 [95%
      confidence interval, 1.00-1.50]). CONCLUSIONS: Overall, this study suggests
      limited to no association between appendectomy and Parkinson's disease risk. (c)
      2018 International Parkinson and Movement Disorder Society.

PMID- 30218461
TI  - Automatic localization of closely spaced cochlear implant electrode arrays in
      clinical CTs.
AB  - PURPOSE: Cochlear implants (CIs) are neural prosthetic devices that provide a
      sense of sound to people who experience profound hearing loss. Recent research
      has indicated that there is a significant correlation between hearing outcomes
      and the intracochlear locations of the electrodes. We have developed an image
      guided cochlear implant programming (IGCIP) system based on this correlation to
      assist audiologists with programming CI devices. One crucial step in our IGCIP
      system is the localization of CI electrodes in postimplantation CTs. Existing
      methods for this step are either not fully automated or not robust. When the CI
      electrodes are closely spaced, it is more difficult to identify individual
      electrodes because there is no intensity contrast between them in a clinical CT.
      The goal of this work is to automatically segment the closely spaced CI electrode
      arrays in postimplantation clinical CTs. METHODS: The proposed method involves
      firstly identifying a bounding box that contains the cochlea by using a reference
      CT. Then, the intensity image and the vesselness response of the VOI are used to
      segment the regions of interest (ROIs) that may contain the electrode arrays. For
      each ROI, we apply a voxel thinning method to generate the medial axis line. We
      exhaustively search through all the possible connections of medial axis lines.
      For each possible connection, we define CI array centerline candidates by
      selecting two points on the connected medial axis lines as the array endpoints.
      For each CI array centerline candidate, we use a cost function to evaluate its
      quality, and the one with the lowest cost is selected as the array centerline.
      Then, we fit an a priori known geometric model of the array to the centerline to
      localize the individual electrodes. The method was trained on 28 clinical CTs of
      CI recipients implanted with three models of closely spaced CI arrays. The
      localization results are compared with the ground truth localization results
      manually generated by an expert. RESULTS: A validation study was conducted on 129
      clinical CTs of CI recipients implanted with three models of closely spaced
      arrays. Ninety-eight percent of the localization results generated by the
      proposed method had maximum localization errors lower than one voxel diagonal of
      the CTs. The mean localization error was 0.13 mm, which was close to the rater's
      consistency error (0.11 mm). The method also outperformed the existing automatic
      electrode localization methods in our validation study. CONCLUSION: Our
      validation study shows that our method can localize closely spaced CI arrays with
      an accuracy close to what is achievable by an expert on clinical CTs. This
      represents a crucial step toward automating IGCIP and translating it from the
      laboratory to the clinical workflow.

PMID- 30218462
TI  - An unanticipated finding on peripheral smear: Blue-green crystals of impeding
      death?

PMID- 30218463
TI  - Rare cause of maternal and neonatal hypercalcaemia.

PMID- 30218464
TI  - Bell's palsy treated with photobiomodulation in an adolescent: Rare case report
      and review of the published literature.
AB  - BACKGROUND: Bell's palsy represents a peripheral unilateral facial nerve
      paralysis, being an acute, idiopathic disorder, which can affect children and
      adolescents. Some therapeutic approaches have been proposed including facial
      exercises, biofeedback, photobiomodulation, electrotherapy, massage, and
      thermotherapy. The present report documents a rare case of Bell's palsy in an
      adolescent successfully treated with a new protocol of photobiomodulation,
      consisting of a short-term treatment. CASE REPORT: A 13-year-old girl presented
      absence of facial movement on the right side when smiling, inability to close the
      right eye and to raise the right eyebrow, intense painful symptoms on the right
      side of the face, difficult in chewing and talking, and sialorrhea. She was
      diagnosed with an idiopathic facial paralysis or Bell's palsy associated with
      right masseter myalgia, and treated with three sessions of photobiomodulation
      using infrared laser, 100 mW output power, 100 J/cm2 of energy density, 28
      seconds per point, applied at the origin and insertion of the right superficial
      masseter muscle. The patient presented complete regression of paralysis,
      improvement of speech and chewing, and absence of muscular pain. CONCLUSION:
      Photobiomodulation was effective to treat Bell's palsy in a pediatric patient,
      being a true noninvasive approach and with no side effects, although there is
      still no established definitive protocol.

PMID- 30218465
TI  - Admission temperature and hospital outcomes in extremely preterm infants.
AB  - AIM: To evaluate trends in admission temperature and its effect on mortality and
      short-term morbidities in extremely preterm infants. METHODS: A regional cohort
      study of infants born at 23-28 weeks' gestation and admitted to the 10 neonatal
      intensive care units in New South Wales and the Australian Capital Territory
      between 1994 and 2012. Hypothermia was defined as skin temperature <36 degrees C
      on admission to the neonatal intensive care unit. The primary outcome was
      hospital mortality. RESULTS: In total, 6267 infants were included. Mean admission
      temperatures improved significantly from 35.6 degrees C in 1994 to 36.4 degrees C
      in 2012 (R < 0.88). The incidence of hypothermia was 29.5 and 13.9% between 1994
      2005 and 2006-2012, respectively. In comparison with normothermic infants,
      hypothermic infants had lower gestational age at birth (26 vs. 27 weeks) and
      lower birthweight (800 vs. 976 g). In-hospital mortality was higher in
      hypothermic infants (28.5 vs. 12.9%; odds ratio (OR) 2.69, 95% confidence
      interval (CI) 2.37-3.06). Severe intraventricular haemorrhage (12.1 vs. 8.5%, OR
      1.48, 95% CI 1.25-1.75), necrotising enterocolitis (NEC) (11.0 vs. 7.5%; OR 1.54,
      95% CI 1.29-1.83) and severe retinopathy of prematurity (16.5 vs. 8.9%; OR 2.02,
      95% CI 1.70-2.39) were significantly higher in hypothermic infants. Multivariate
      regression analysis showed hypothermia was an independent risk factor for
      increased mortality (AOR (adjusted odds ratio ) 1.50, 95% CI 1.29-1.74, P <
      0.001) and NEC (AOR 1.28, 95% CI 1.05-1.55, P = 0.01). CONCLUSIONS: Admission
      temperatures improved during the time period. Hypothermia at admission was
      associated with a significant increase in mortality and NEC.

PMID- 30218466
TI  - Albuminuria and low bone mineral density in paediatric patients with type 1
      diabetes.
AB  - AIM: To evaluate glycaemic control and its influence on albuminuria and bone
      mineral density (BMD) in children and adolescents with type 1 diabetes (T1D).
      METHODS: We collectively assessed 84 T1D children/adolescents (T1D group), aged
      between 6 and 17 years, and then divided them into two groups according to their
      glycaemic profile (T1D with good glycaemic control (T1DG group) and T1D with poor
      glycaemic control (T1DP group)). Serum glucose, glycated haemoglobin, serum urea,
      serum creatinine, urinary albumin-to-creatinine ratio (ACR), estimated glomerular
      filtration rate and BMD levels were assessed. RESULTS: Of the patients studied,
      77% presented with poor glycaemic control. Patients with T1DP showed an increased
      ACR (P < 0.001) and a low BMD (P = 0.025) when compared to the T1DG group. In
      addition, five patients in the T1DP group presented with concomitant albuminuria
      and a low BMD for their chronological age. Significant negative correlations were
      identified between the ACR and glycated haemoglobin (r = 0.655, P < 0.001), BMD
      and glycated haemoglobin (r = -0.262, P = 0.047) and BMD and the ACR (r = -0.631,
      P = <0.001). In linear regression analysis, the ACR showed a negative effect on
      BMD (P = 0.044) in the T1D patient group. CONCLUSION: Poor glycaemic control was
      correlated with albuminuria, suggestive of a negative effect on bone tissue,
      leading to a low BMD in children and adolescents with T1D.

PMID- 30218468
TI  - Social behaviours by Bacillus subtilis: quorum sensing, kin discrimination and
      beyond.
AB  - Here, we review the multiple mechanisms that the Gram-positive bacterium Bacillus
      subtilis uses to allow it to communicate between cells and establish community
      structures. The modes of action that are used are highly varied and include
      routes that sense pheromone levels during quorum sensing and control gene
      regulation, the intimate coupling of cells via nanotubes to share cytoplasmic
      contents, and long-range electrical signalling to couple metabolic processes both
      within and between biofilms. We explore the ability of B. subtilis to detect
      'kin' (and 'cheater cells') by looking at the mechanisms used to potentially
      ensure beneficial sharing (or limit exploitation) of extracellular 'public
      goods'. Finally, reflecting on the array of methods that a single bacterium has
      at its disposal to ensure maximal benefit for its progeny, we highlight that a
      large future challenge will be integrating how these systems interact in mixed
      species communities.

PMID- 30218467
TI  - TKSA-MC: A web server for rational mutation through the optimization of protein
      charge interactions.
AB  - The TKSAMC is a web server which calculates protein charge-charge interactions
      via the Tanford-Kirkwood Surface Accessibility model with the Monte Carlo method
      for sampling different protein protonation states. The optimization of charge
      charge interactions via directed mutations has successfully enhanced the thermal
      stability of different proteins and could be a key to protein engineering
      improvement. The server presents the electrostatic free energy contribution of
      each polar-charged residue to the protein native state stability. Specific
      residues are suggested to be mutated for improving thermal stability. The choice
      of a residue is based on its fraction of side chain exposed to solvent and its
      positive free energy contribution, which tends to destabilize the protein native
      state. Any residue energy contribution can be shown as a function of pH
      condition. The web server is freely available at UNESP (Sao Paulo State
      University - DF/IBILCE): http://tksamc.df.ibilce.unesp.br and also on GitHub
      https://github.com/contessoto/tksamc.

PMID- 30218469
TI  - Use of chronic total occlusion percutaneous coronary intervention techniques for
      treating acute vessel closure.
AB  - Acute vessel closure due to dissection is a known complication of percutaneous
      coronary intervention and can be challenging to treat, especially if guidewire
      position is lost. Re-entering into the distal true lumen is commonly done during
      chronic total occlusion interventions, as part of antegrade dissection
      strategies. We report two cases of acute vessel closure and guidewire position
      loss in which the Stingray LP system was successfully used to advance a guidewire
      into the distal true lumen and recanalize the occluded vessel.

PMID- 30218470
TI  - Insights into respiratory disease through bioinformatics.
AB  - Respiratory diseases such as asthma, chronic obstructive pulmonary disease and
      lung cancer represent a critical area for medical research as millions of people
      are affected globally. The development of new strategies for treatment and/or
      prevention, and the identification of biomarkers for patient stratification and
      early detection of disease inception are essential to reducing the impact of lung
      diseases. The successful translation of research into clinical practice requires
      a detailed understanding of the underlying biology. In this regard, the advent of
      next-generation sequencing and mass spectrometry has led to the generation of an
      unprecedented amount of data spanning multiple layers of biological regulation
      (genome, epigenome, transcriptome, proteome, metabolome and microbiome). Dealing
      with this wealth of data requires sophisticated bioinformatics and statistical
      tools. Here, we review the basic concepts in bioinformatics and genomic data
      analysis and illustrate the application of these tools to further our
      understanding of lung diseases. We also highlight the potential for data
      integration of multi-omic profiles and computational drug repurposing to define
      disease subphenotypes and match them to targeted therapies, paving the way for
      personalized medicine.

PMID- 30218471
TI  - Mind the body to detect embodiment in the mind.

PMID- 30218473
TI  - Paediatric electroencephalograph: The benefits of guidelines.
AB  - AIM: The electroencephalogram (EEG) is an important but often over-relied upon
      investigation in evaluating paroxysmal events of childhood. The UK National
      Institute for Health and Care Excellence (NICE) guidelines for epilepsy help
      clinicians decide which children should/should not have an EEG. Would
      introduction of these guidelines in our hospital change the ordering practices of
      our hospital clinicians? Would introduction reduce unnecessary tests and improve
      rapidity of obtaining an EEG? METHODS: Paediatric EEG requests, results and,
      where possible, the patient hospital chart were reviewed before and after
      introduction of an EEG request form (Appendix I) which provided ordering advice
      as per the NICE epilepsy guideline. Patient age, sex, distance from hospital and
      ethnicity were reviewed. Also evaluated was clinical indication and time from
      ordering to performing the EEG. RESULTS: Prior to the new EEG form, 56% of the
      EEG requests fulfilled the NICE criteria; after its introduction, this increased
      to 83%. EEGs ordered within the NICE guidelines were abnormal on 61% of
      occasions, but when ordered outside of the guidelines they were abnormal only 4%
      of the time (P < 0.0001). After its introduction there was poor use of the new
      form in practice (only 29% of requests). However, the EEGs were more likely to
      meet ordering criteria and fewer tests were required, leading to more rapid turn
      around times. CONCLUSION: This study demonstrates the value of using guidelines
      to improve timeliness and reduce over-utilisation of EEGs in general paediatric
      practice.

PMID- 30218474
TI  - The prevalence of computed tomography-defined leaflet thrombosis in intra- versus
      supra-annular transcatheter aortic valve prostheses.
AB  - INTRODUCTION: Leaflet thrombosis (LT) defined by computed tomography (CT)
      following transcatheter aortic valve replacement (TAVR) has been shown to
      increase cerebrovascular events. The neo-sinus plays an important role in the
      development of LT. Intra-annular valves (IAV) have a larger neo-sinus when
      compared to supra-annular valves (SAV), and has been associated with larger
      thrombus burden. The prevalence of LT with IAV and SAV in a larger, diverse
      cohort is unknown. METHODS: We performed a systematic review to assess the
      prevalence of LT in IAV versus SAV TAVR prostheses. Inclusion criteria were (1)
      reported CT-defined LT following TAVR, (2) comparison between LT and non-LT
      cohort, (3) separate registry/database, and (4) fully published status. A total
      of 2,013 citations were reviewed and 7 studies were included. RESULTS: Overall,
      1,644 patients were included from 7 observational studies and the prevalence of
      LT following TAVR was 12.8%. The Portico valve system (IAV) had the highest
      prevalence of LT with 35.2%, followed by Symetis Acurate Neo (SAV) at 15.4% and
      the Lotus valve system (IAV) at 14.5%. LT occurred more frequently in IAV than
      SAV (13.5% vs. 7%, P = 0.02). Subanalysis of IAV versus SAV with the exclusion of
      the Portico valve was performed to ensure results were not influenced by this
      valve system and revealed IAV still had higher rates of LT (12.1% vs. 7%, P =
      0.05). CONCLUSION: In summary, IAV prostheses appear to be associated with higher
      rates of LT when compared with SAV.

PMID- 30218472
TI  - Proteolysis of ToxR is controlled by cysteine-thiol redox state and bile salts in
      Vibrio cholerae.
AB  - In Vibrio cholerae, virulence gene expression is regulated by a transmembrane
      localized transcription factor complex designated as ToxRS. ToxR harbours two
      cysteines in the periplasmic domain that can form inter- and intramolecular
      disulfide bonds. In this study, we investigated the sigmaE -dependent inner
      membrane proteolysis of ToxR, which occurs via the periplasmic-localized
      proteases DegS and DegP. Both proteases respond to the redox state of the two
      cysteine thiol groups of ToxR. Interestingly, in the presence of sodium
      deoxycholate, ToxR proteolysis is blocked independently of ToxS, whereas ToxR
      activation by bile salts requires ToxS function. From these data, we identified
      at least two levels of control for ToxR activation by sodiumdeoxycholate. First,
      bile inhibits ToxR degradation under starvation and alkaline pH or under
      conditions in which DegPS responds to the reduced disulfide bonds of ToxR. The
      second level links bile to ToxRS complex formation and further activation of its
      transcription factor activity. Overall, our data suggest a comprehensive bile
      sensory function for the ToxRS complex during host colonization.

PMID- 30218475
TI  - Liquid-Phase Synthesis of Boron Isocyanates: Precursors to Boron Nanoparticles.
AB  - The practical application of boron isocyanates has been hindered by their
      extremely high sensitivity and reactivity toward air and moisture. A convenient
      synthetic method in a suitable liquid media is reported for practical utilization
      of boron isocyanates. According to NMR studies, the in situ generated boron
      isocyanates can be stored for at least one month under an inert atmosphere at -20
      degrees C without noticeable decomposition. The boron tri(isocyanate) (B(NCO)3 )
      was converted into boron nanoparticles by reduction with hydrogen under mild
      reaction conditions.

PMID- 30218476
TI  - Robust interferon signature and suppressed tissue repair gene expression in
      synovial tissue from patients with postinfectious, Borrelia burgdorferi-induced
      Lyme arthritis.
AB  - In most patients with Lyme arthritis (LA), antibiotic therapy results in Borrelia
      burgdorferi pathogen elimination, tissue repair, and return to homeostasis.
      However, despite spirochetal killing, some patients develop proliferative
      synovitis, characterised by synovial hyperplasia, inflammation, vascular damage,
      and fibrosis that persists for months to several years after antibiotic
      treatment, called postinfectious LA. In this study, we characterised the
      transcriptomes of postinfectious LA patients' synovial tissue, the target tissue
      of the immune response. High-throughput RNA sequencing to a depth of ~30 million
      reads per sample was used to profile gene expression in synovial tissue from 14
      patients with postinfectious LA, compared with eight patients with other types of
      chronic inflammatory arthritis and five with minimally inflammatory
      osteoarthritis (OA). Synovium from postinfectious LA and other inflammatory
      arthritides shared gene signatures associated with antigen presentation, innate
      immune responses, and cell-mediated immune activation, whereas these responses
      were diminished in OA synovium. Unique to postinfectious LA was a particularly
      robust interferon-gamma (IFNgamma) signature. Moreover, this heightened IFNgamma
      signature inversely correlated with expression of genes involved in repair of
      damaged tissue, including genes associated with stromal cell proliferation and
      differentiation, neovascularisation, and extracellular matrix synthesis, which
      were markedly suppressed in postinfectious LA. Transcriptional observations were
      confirmed by cytokine profiling, histologic analyses, and clinical correlations.
      We propose that in patients with postinfectious LA, overexpression of IFNgamma in
      synovium prevents appropriate repair of tissue damaged by B. burgdorferi
      infection, blocking return to tissue homeostasis long after completion of
      antibiotic therapy and resolution of active infection.

PMID- 30218478
TI  - Transitions in nutation trajectory geometry in peppermint (Mentha x piperita L.)
      with respect to lunisolar acceleration.
AB  - Nutations of plant organs are significantly affected by the circatidal modulation
      in the gravitational force exerted by the Moon and Sun (lunisolar tidal
      acceleration, Etide). In a previous study on nutational rotations of stem apices,
      we observed abrupt alterations in their direction and irregularities of the
      recorded trajectories. Such transitions have not yet been analysed in detail.
      Peppermint plants were continuously recorded with time-lapse photography and
      aligned with contemporaneous time courses of the Etide estimates. Each nutational
      stem tip movement path was assigned to one of two groups, depending on its
      geometry, as: (i) regular elliptical movements and (ii) irregular movements (with
      a random type of trajectory). Analyses of the correlation between the plant
      nutation trajectory parameters and Etide, as well as of the trajectory geometry
      of the individual plants were performed. The trajectory geometry of young mint
      stem apices was related to the velocity of the apex rotation and significantly
      affected by the gravitational force estimated from the Etide. A low velocity of
      nutational movement, associated with the random character of the trajectory,
      usually occurred simultaneously with local minima or maxima of Etide. As the mint
      plant ages, the transitions in the stem tip trajectory were limited; no
      correspondence with Etide dynamics was observed. The results indicate that the
      plant tip geometry path transitions with respect to the changing gradient of
      lunisolar tidal acceleration could be interpreted as manifestation of a
      continuous accommodation of the shoot apical part to the state of minimum energy
      dissipation.

PMID- 30218477
TI  - Temporomandibular joint anterior disc displacement with reduction in a young
      population: Prevalence and risk indicators.
AB  - BACKGROUND: Temporomandibular joint (TMJ) anterior disc displacements with
      reduction (ADDR) are commonly found in the young population and often found to be
      associated with biomechanical and anatomical factors. Until now, most knowledge
      on ADDR among children and adolescents comes from studies performed on Caucasian
      subjects. AIMS: To assess the clinically determined prevalence rates of ADDR
      among the young Indonesian population and to evaluate its risk indicators.
      DESIGN: In this cross-sectional study, 1562 pupils and students of 7-21 years old
      completed a questionnaire and underwent a clinical examination. RESULTS: The
      prevalence rates of ADDR were 7.0% among children (7-12 years), 14.4% among
      adolescents (13-18 years), and 12.3% among young adults (19-21 years). Logistic
      regression analyses revealed that increasing age and lip biting were associated
      with ADDR in children, whereas pen biting was associated with ADDR in the
      adolescent population. None of the included factors were found to be associated
      with ADDR in the young adult population. CONCLUSIONS: The present findings
      indicate that prevalence of ADDR increases with age, with a peak during the years
      of adolescence. Biomechanical factors seem to play a significant role in ADDR
      development.

PMID- 30218479
TI  - Responsiveness of the Brazilian versions of CPQ11-14 and Child-OIDP.
AB  - AIM: The aim of this study was to investigate the responsiveness of the Brazilian
      versions of Child Perceptions Questionnaire (CPQ11-14 ) and Child-Oral Impacts on
      Daily Performances (Child-OIDP). DESIGN: The data were collected from a
      convenience sample of 209 patients aged 10-15 years, who visited the adolescent
      dental clinic of Federal University of Santa Maria, Brazil. The subjects answered
      the CPQ11-14 and the Child-OIDP prior to their dental treatment and 1 month after
      concluding the treatment. The responsiveness of CPQ11-14 and Child-OIDP was
      analysed through (a) the mean change observed in scores before and after
      treatment, (b) an investigation of the effect size, (c) an assessment of the
      statistical significance of changes within the groups over time, as per the
      global transition judgement, and (d) the receiver operating characteristic (ROC)
      curve. RESULTS: Positive changes were observed for both questionnaires. According
      to global transition judgement, 82.30% of the participants reported an
      improvement following treatment, 16.75% reported no change, and 0.96% reported
      deterioration. The effect size was 0.8% and 0.5% for the overall CPQ11-14 and
      Child-OIDP, respectively. The area under the curve was 0.38 for CPQ11-14 and 0.43
      for Child-OIDP. CONCLUSION: The Brazilian versions of CPQ11-14 and Child-OIDP
      demonstrated limited responsiveness following dental treatment.

PMID- 30218480
TI  - Emotions experienced during the shedding of the first primary tooth.
AB  - AIM: To examine the different emotions expressed by children exfoliating their
      first primary tooth, evaluate their proportional distribution, and reveal
      possible influences of child- and parent-related variables on the reported
      emotions. DESIGN: A cross-sectional questionnaire was directed to parents of
      children who had recently shed at least one primary tooth. Primary outcome
      variables were the child's emotions at the time of exfoliation. Child-related
      determinants were sex, duration of tooth wiggle, previous accident- or caries
      related visits at dentist, and having witnessed tooth exfoliation in older
      siblings. Parent-related determinants included socio-economic variables
      (education, religion, country of origin). RESULTS: One thousand two hundred and
      seventy-four of 3617 questionnaires were returned and analysed (35.2%). 82.0% of
      the parents reported positive, and 22.0% negative emotions in their child.
      Previous caries-related visits at the dentist diminished the likelihood of
      positive emotions (OR = 0.65), and accident-related visits increased the odds of
      positive emotions (OR = 1.57), as did an extended duration of tooth wiggle (OR =
      1.98). Higher education of mothers (OR = 2.89) and fathers (OR = 1.96) and an
      origin from non-Western countries (OR = 2.56 and OR = 1.85, respectively) were
      also related to positive emotions. CONCLUSIONS: For most children, losing the
      first primary tooth is associated with positive emotions. Dental visits and
      parental factors influence these emotions. Parents and dentists should be aware
      of their impact on children's emotional development.

PMID- 30218481
TI  - Adherence to a Mediterranean diet, lifestyle and age-related macular
      degeneration: the Coimbra Eye Study - report 3.
AB  - PURPOSE: To characterize the lifestyle and nutritional risk profile associated
      with the Mediterranean diet in a Portuguese population with and without age
      related macular degeneration (AMD). METHODS: Nested case-control study (n = 883)
      within the Coimbra Eye Study, including 434 subjects with AMD and 449 age- and
      sex-matched subjects without AMD. All enrolled subjects underwent a full risk
      assessment, including lifestyle-related risk factors and a thorough food
      frequency questionnaire. This allowed us to build an adherence score to the
      Mediterranean diet (mediSCORE, range 0-9) constructed from individual food
      intakes. Food intake was also further analysed by conversion to micronutrient
      consumption. RESULTS: Our results suggest that physical activity has a protective
      role in AMD [p = 0.018 after multivariate adjustment, OR: 0.69 (0.51-0.93)]. High
      (mediSCORE >=6) was also found to be protective [p = 0.041, OR: 0.62 (95% CI:
      0.38-0.97)]. Food group analysis unveiled a specific protective role for
      increased fruits consumption (p = 0.029). Finally, micronutrient analysis
      revealed a protective role associated with increased consumption of caffeine,
      fibres, beta-carotene, vitamin C and vitamin E (p < 0.05). CONCLUSION: High
      mediSCORE appears to confer protection against the development of AMD in a
      Mediterranean population. This effect is driven by increased consumption of
      fruits and some antioxidant micronutrients, which emerged as statistically
      significant protective factors. Further studies are required to establish dietary
      recommendations with clinical application.

PMID- 30218482
TI  - Para-perirenal distribution of body fat is associated with reduced glomerular
      filtration rate regardless of other indices of adiposity in hypertensive
      patients.
AB  - Obesity is a well-known risk factor for the development and progression of
      chronic kidney disease. Recently, para-perirenal ultrasonographic fat thickness
      (PUFT) has shown to correlate with both total and visceral fat better than body
      mass index (BMI), waist circumference (WC), and other indices of obesity.
      Moreover, a local paracrine and mechanical action of the PUFT on kidney has been
      described in recent studies. Aim of our study was to assess the relationship
      between glomerular filtration rate (GFR) and PUFT in comparison with other
      anthropometric and ultrasonographic indices of adiposity. Two hundred and ninety
      six hypertensive patients were enrolled. PUFT, cutis-rectis thickness and rectis
      aorta thickness were obtained by ultrasonography. Anthropometric measures of
      adiposity were also measured. Estimated GFR was calculated using the CKD-EPI
      equation. Higher PUFT values were observed in patients with impaired renal
      function (P < 0.001), whereas no differences in BMI and WC were shown between
      groups divided by GFR. PUFT significantly correlated with GFR in all patients (r
      = -0.284; P < 0.001), with no differences in groups divided by sex, diabetes, or
      BMI. This association held in multivariate analyses also after correction for
      confounding factors, including other adiposity indices (P < 0.001). When receiver
      operating characteristic curves were built to detect a eGFR < 60 mL/minutes per
      1.73 m2 , a PUFT value <=3.725 cm showed a negative predictive value of 94.0%,
      with the largest area under the curve (AUC: 0.700) among the variables
      considered. In conclusion, the relationship between PUFT and GFR seems to be more
      accurate and less influenced by the bias affecting traditional indices of
      adiposity.

PMID- 30218484
TI  - Electroretinogram abnormalities in nonanterior childhood uveitis.
AB  - PURPOSE: A major point of concern in uveitis is the development of irreversible
      retinal changes after inflammation. In this study, we assess how nonanterior
      childhood uveitis affects retinal function using full-field electroretinography
      (ERG). METHODS: Cross-sectional study. ERGs of 63 uveitis eyes (33 children) were
      measured according to extended International Society for Clinical
      Electrophysiology of Vision (ISCEV) protocols. ERG abnormalities were
      investigated in relation to the following clinical parameters: demographics,
      uveitis characteristics, including severity of inflammation, treatment, best
      corrected visual acuity (BCVA), cystoid macular oedema (CME) on optical coherence
      tomography and fluorescein angiography score. RESULTS: The ERG showed
      abnormalities in 34 eyes (54%). The most frequent ERG abnormalities were
      prolonged implicit times of the cone b-wave (37%; n = 23/63) and an abnormal 30
      Hz flicker response (implicit time and/or amplitude) (33%; n = 21/63). Factors
      associated with these ERG abnormalities were CME (p = 0.021) and 3+ vitreous
      cells (p = 0.021). BCVA in eyes with and without these ERG abnormalities did not
      statistically differ and was relatively good (median: 0.05 LogMAR, IQR: 0.00-0.15
      LogMAR). CONCLUSION: The ERG is frequently affected in childhood uveitis
      indicating a global retinal dysfunction. ERG abnormalities seem to be associated
      with a more severe posterior segment inflammation and a younger age. If an
      association between ERG abnormalities and long-term visual outcome can be made in
      the future, these early ERG findings during the course of childhood uveitis have
      significance for treatment strategies.

PMID- 30218483
TI  - Neuropeptide Y treatment induces retinal vasoconstriction and causes functional
      and histological retinal damage in a porcine ischaemia model.
AB  - PURPOSE: To investigate the effects of intravitreal neuropeptide Y (NPY)
      treatment following acute retinal ischaemia in an in vivo porcine model. In
      addition, we evaluated the vasoconstrictive potential of NPY on porcine retinal
      arteries ex vivo. METHODS: Twelve pigs underwent induced retinal ischaemia by
      elevated intraocular pressure clamping the ocular perfusion pressure at 5 mmHg
      for 2 hr followed by intravitreal injection of NPY or vehicle. After 4 weeks,
      retinas were evaluated functionally by standard and global-flash multifocal
      electroretinogram (mfERG) and histologically by thickness of retinal layers and
      number of ganglion cells. Additionally, the vasoconstrictive effects of NPY and
      its involved receptors were tested using wire myographs and NPY receptor
      antagonists on porcine retinal arteries. RESULTS: Intravitreal injection of NPY
      after induced ischaemia caused a significant reduction in the mean induced
      component (IC) amplitude ratio (treated/normal eye) compared to vehicle-treated
      eyes. This reduction was accompanied by histological damage, where NPY treatment
      reduced the mean thickness of inner retinal layers and number of ganglion cells.
      In retinal arteries, NPY-induced vasoconstriction to a plateau of approximately
      65% of potassium-induced constriction. This effect appeared to be mediated via Y1
      and Y2, but not Y5. CONCLUSION: In seeming contrast to previous in vitro studies,
      intravitreal NPY treatment caused functional and histological damage compared to
      vehicle after a retinal ischaemic insult. Furthermore, we showed for the first
      time that NPY induces Y1- and Y2- but not Y5-mediated vasoconstriction in retinal
      arteries. This constriction could explain the worsening in vivo effect induced by
      NPY treatment following an ischaemic insult and suggests that future studies on
      exploring the neuroprotective effects of NPY might focus on other receptors than
      Y1 and Y2.

PMID- 30218485
TI  - Replacement of neuraminidase inhibitor-susceptible influenza A(H1N1) with
      resistant phenotype in 2008 and circulation of susceptible influenza A and B
      viruses during 2009-2013, South Africa.
AB  - BACKGROUND: Data on the susceptibility of influenza viruses from South Africa to
      neuraminidase inhibitors (NAIs) are scarce, and no extensive analysis was done.
      OBJECTIVES: We aimed to determine oseltamivir and zanamivir susceptibility of
      influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa.
      PATIENTS/METHODS: We enrolled participants through national influenza-like
      illness surveillance, 2007-2013. Influenza diagnosis was by virus isolation and
      quantitative polymerase chain reaction (qPCR). Drug susceptibility was determined
      by chemiluminescence-based NA-STAR/NA-XTD assay. Sanger sequencing was used to
      determine molecular markers of NAI resistance. RESULTS: Forty percent (6341/15
      985) of participants were positive for influenza viruses using virus isolation
      (2007-2009) and qPCR (2009-2013) methods. A total of 1236/6341 (19.5%) virus
      isolates were generated of which 307/1236 (25%) were tested for drug
      susceptibility. During 2007-2008, the median 50% inhibitory concentration (IC50 )
      of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nmol/L
      (range 0.01-3.60) in 2007 to 73 nmol/L (range 1.56-305 nmol/L) in 2008. Influenza
      A isolates from 2009 to 2013 were susceptible to oseltamivir [A(H3N2) median IC50
      = 0.05 nmol/L (range 0.01-0.08); A(H1N1)pdm09 = 0.11 nmol/L (range 0.01-0.78)]
      and zanamivir [A(H3N2) median IC50  = 0.56 nmol/L (range 0.47-0.66); A(H1N1)pdm09
      = 0.35 nmol/L (range 0.27-0.533)]. Influenza B viruses were susceptible to both
      NAIs. NAI resistance-associated substitutions H275Y, E119V, and R150K (N1
      numbering) were not detected in influenza A viruses that circulated in 2009-2013.
      CONCLUSIONS: We confirm replacement of NAI susceptible by resistant phenotype
      influenza A(H1N1) in 2008. Influenza A and B viruses (2009-2013) remained
      susceptible to NAIs; therefore, these drugs are useful for treating influenza
      infected patients.

PMID- 30218486
TI  - Autonomic nervous system might be related with circadian rhythms and have the
      intricate effects in obstructive sleep apnea with metabolic syndrome.

PMID- 30218487
TI  - Design, synthesis, and biological activity evaluation of campthothecin-HAA
      Norcantharidin conjugates as antitumor agents in vitro.
AB  - Three components of Camptothecin, hydroxyacetic acid, and functionalized
      norcantharidins were constructed together to form a novel series of camptothecin
      derivatives in a good yield. The synthesized campthothecin-HAA-norcantharidin
      conjugate pro-drugs could suppress cancer cell growth in vitro. These conjugated
      pro-drug molecules possess therapeutic potential as novel bi-functional
      conjugates platforms for cancer treatment.

PMID- 30218489
TI  - Analysis of the current preschool vision screening in Denmark.
AB  - PURPOSE: To analyse the current vision screening programme for children attending
      school with respect to identifying children with significant refractive errors.
      METHODS: A total of 950 children from the municipality of Roskilde, Denmark, were
      invited to participate in a cross-sectional study of vision screening. 447
      children aged 4.5-7 years participated in the study. The children completed a
      vision screening and a full eye examination. The vision screening consisted of
      visual acuity at distance (VA), visual acuity at distance with +2.0 glasses
      (VA+2), visual acuity at near (VAnear) and Lang II stereotest. A LogMAR-based
      picture chart was used for the vision testing. Significant refractive errors were
      defined as hyperopia >=+3.5 D, myopia >1.0 D, astigmatism >=1.25 D and
      anisometropia >1.0 D. RESULTS: Using receiver operating characteristic (ROC)
      curves, we could compare the efficiency of VA, VA+2, VAnear, VA in combination
      with VA+2 and VA in combination with VAnear. Area under the curve (AUC) for VA,
      VA combined with VA+2 and VA combined with VAnear was 0.841, 0.857 and 0.857,
      respectively, that is all classified as 'very good' screening tools, whereas VA+2
      and VAnear as single screening tools were classified as 'good' with AUC of 0.704
      and 0.775, respectively. Using the optimal cut-off limit from the ROC curves, VA
      above 0.05 LogMAR as cut-off limit showed a sensitivity of 85.2% with a
      specificity of 74.9%. A slightly higher sensitivity could be found when combining
      screening tests, but with declining specificities. CONCLUSION: Visual acuity at
      distance with the use of LogMAR-based charts is the optimal screening tool of
      choice; only minor improvements can be obtained combining with other tests.

PMID- 30218488
TI  - Optimal positioning of self-expanding valves before deployment decreases
      paravalvular regurgitation following transcatheter aortic valve replacement.
AB  - OBJECTIVES: To evaluate the association between measurements performed during
      Medtronic CoreValve (MCV) deployment and paravalvular leak (PVL). BACKGROUND: The
      MCV can be recaptured and repositioned, allowing the TAVR operator to implant at
      a more favorable position. The association between angiographic measurements of
      MCV position while the valve is recapturable and PVL post deployment has not been
      investigated. METHODS: 493 patients undergoing TAVR with MCV (January 2011-July
      2017) were included. PVL was defined as intraprocedural aortic regurgitation that
      was judged clinically to require balloon postdilation. Depth of the valve at the
      left coronary cusp (LCC) and noncoronary cusp (NCC) were measured when the valve
      was 80% deployed. An optimal cutoff value for the ratio LCC/NCC for PVL was
      identified in 40 patients. Using this cutoff value, the association between
      LCC/NCC and PVL was then validated in 453 patients. RESULTS: The median LCC/NCC
      was 1.51 (interquartile range 1.06-1.89).The optimal cutoff value for LCC/NCC was
      1.48 (93% sensitivity, 77% specificity, AUC0.85). In the validation group 112
      (24.7%) patients had PVL. For LCC/NCC >= 1.48, the incidence of PVL was lower
      compared to LCC/NCC < 1.48 (9.58% vs. 41.78%, P < 0.0001). LCC/NCC of 1.48 had a
      sensitivity of 79.5% and specificity of 63.6% for PVL (AUC0.72). In a
      multivariate model, LCC/NCC < 1.48 independently predicted PVL (OR = 6.67, 95% CI
      3.96-11.23, P < 0.0001). CONCLUSION: Positioning the MCV such that the LCC/NCC is
      >=1.48 may result in less PVL.

PMID- 30218490
TI  - Binocular vision alterations after refractive and cataract surgery: a review.
AB  - To review binocular and accommodative disorders documented after corneal or
      intraocular refractive surgery, in normal healthy prepresbyopic patients. A
      bibliographic revision was performed; it included works published before 1st July
      2017 where accommodation and/or binocularity was assessed following any type of
      refractive surgical procedure. The search in Pubmed yielded 1273 papers, 95 of
      which fulfilled the inclusion criteria. Few publications reporting binocular
      vision and/or accommodative changes after refractive surgery in normal subjects
      were found. The reduction in fusional vergence is the most frequently reported
      alteration. Anisometropia is an important risk factor for postoperative binocular
      vision-related complaints. Most diplopia-related visual complaints, irrespective
      of the surgical procedure, were in fact misdiagnosed preoperative disorders. The
      preoperative evaluation of patients seeking spectacle/contact lens independence
      should include a complete binocular and accommodation assessment where parameters
      such as the phoric posture, accommodative amplitude and facility, near point of
      convergence, fusional reserves and accommodative convergence/accommodation
      coefficient are measured. This would allow the identification of risk factors
      that could compromise the success of the refractive surgery and cause clinical
      symptoms.

PMID- 30218491
TI  - Circadian rhythms might be the key joint role in intricate effects among
      metabolic syndrome, obstructive sleep apnea, and hypertension.

PMID- 30218492
TI  - Biophysical screening methods for extracellular domain peptide receptors,
      application to natriuretic peptide receptor C ligands.
AB  - Endothelium-derived C-type natriuretic peptide possesses cytoprotective and anti
      atherogenic functions that regulate vascular homeostasis. The vasoprotective
      effects of C-type natriuretic peptide are somewhat mediated by the natriuretic
      peptide receptor C, suggesting that this receptor represents a novel therapeutic
      target for the treatment of cardiovascular diseases. In order to facilitate our
      drug discovery efforts, we have optimized an array of biophysical methods
      including surface plasmon resonance, fluorescence polarization and thermal shift
      assays to aid in the design, assessment and characterization of small molecule
      agonist interactions with natriuretic peptide receptors. Assay conditions are
      investigated to explore the feasibility and dynamic range of each method, and
      peptide-based agonists and antagonists are used as controls to validate these
      conditions. Once established, each technique was compared and contrasted with
      respect to their drug discovery utility. We foresee that such techniques will
      facilitate the discovery and development of potential therapeutic agents for NPR
      C and other large extracellular domain membrane receptors.

PMID- 30218493
TI  - Increased risk of neovascular age-related macular degeneration in patients with
      herpes zoster ophthalmicus: a retrospective cohort study.

PMID- 30218494
TI  - The rim area of the optic nerve head, assessed with Heidelberg retina tomography,
      is smaller in prematurely born children than in children born at term.
AB  - PURPOSE: To examine the optic nerve head with Heidelberg tomography (HRT) in
      prematurely born school-age children and compare them to children born at term.
      METHODS: Sixty-three 5-16-year-old children born with a gestational age (GA) of
      <=32 weeks were included in the study and compared to 54 children of the same
      age, born at term. In the preterm group, 29 children had had retinopathy of
      prematurity (ROP) and nine children had neurological complications. The optic
      nerve head was assessed with HRT. Three measurements were performed, and the
      different topographic parameters were noted. RESULTS: Rim area of the optic nerve
      was significantly smaller in prematurely born children than in children born at
      term. The mean difference was 0.146 mm2 (p = 0.02). No difference between the
      groups was found regarding disc area or cup area. In the preterm group, both disc
      and rim areas were reduced with increasing GA. No correlations with birthweight,
      ROP or neurological complications were found. CONCLUSION: Reduced rim area of the
      optic nerve head was found in preterm children of school age. Previous ROP or
      neurological complication did not influence the result, suggesting the preterm
      birth per se was the reason for the reduction. Establishing whether this finding
      was caused by disturbed maturation of the optic nerve or by injury of the axons,
      or a combination of the two, will require further research.

PMID- 30218495
TI  - Ex vivo magnifying endoscopic observation of bile duct mucosa using narrowband
      imaging.
AB  - BACKGROUND: Detailed endoscopic findings of the bile duct mucosa have not been
      fully established. This fundamental ex vivo study assesses the relationship
      between magnified endoscopic findings and pathological findings of the bile duct
      mucosa. METHODS: Forty-one surgically resected common bile duct mucosae were
      investigated. Each common bile duct was cut open longitudinally for ex vivo
      endoscopic observation. A magnifying endoscope commonly used for the
      gastrointestinal tract was used, using both white light imaging and narrowband
      imaging. After pathological diagnosis, the association between the magnifying
      endoscopic findings and histopathology was evaluated. RESULTS: Totally, 39 non
      neoplastic mucosae and 13 neoplastic mucosae were evaluated. In 13 non-neoplastic
      mucosae without inflammation, an oval-shaped depressed area and a fine, regular
      network of microvessels were observed. These findings were not clearly seen or
      not seen at all in the non-neoplastic mucosae with inflammation. Although vessels
      with loop-like structure were observed on all eight papillary tumors of 13
      neoplastic mucosae, no characteristic vessels were seen on the other five.
      CONCLUSIONS: Ishida and colleagues assessed the association between magnifying
      endoscopic findings and histopathological findings of the bile duct mucosa ex
      vivo. Oval-shaped, depressed areas and a fine, regular network of microvessels
      are characteristic features of normal bile duct mucosa, while loop structures may
      be indicative of a type of tumor vessel.

PMID- 30218496
TI  - Intrinsically Disordered Proteins: The Dark Horse of the Dark Proteome.
AB  - A good portion of the 'protein universe' embodies the 'dark proteome'. The latter
      comprises proteins not amenable to experimental structure determination by
      existing means and inaccessible to homology modeling. Hence, the dark proteome
      has remained largely unappreciated. Intrinsically disordered proteins (IDPs) that
      lack rigid 3D structure are a major component of this dark proteome across all
      three kingdoms of life. Despite lack of structure, IDPs play critical roles in
      numerous important biological processes. Furthermore, IDPs serve as crucial
      constituents of proteinaceous membrane-less organelles (PMLOs), where they often
      serve as drivers and controllers of biological liquid-liquid phase transitions
      responsible for the PMLO biogenesis. In this perspective, the role of IDPs is
      discussed in i) the origin of prebiotic life and the evolution of the first
      independent primordial living unit akin to Tibor Ganti's chemoton, which preceded
      the Last Universal Common Ancestor (LUCA), ii) role in multicellularity and
      hence, in major evolutionary transitions, and iii), their role in phenotypic
      switching, and the emergence of new traits and adaptive opportunities via non
      genetic, protein-based mechanisms. The emerging picture suggests that despite
      being major constituents of the dark matter, IDPs may be the dark horse in the
      protein universe.

PMID- 30218498
TI  - What the neighbors say.

PMID- 30218499
TI  - Optic nerve head blood flow regulation during changes in arterial blood pressure
      in patients with primary open-angle glaucoma.
AB  - PURPOSE: Abnormal autoregulation of optic nerve head blood flow (ONHBF) has been
      postulated to play an important role in primary open-angle glaucoma (POAG). We
      used laser Doppler flowmetry (LDF) to estimate quantitatively the ONHBF and
      compared ONHBF autoregulation between glaucoma patients and healthy controls
      during isometric exercise. METHODS: Forty patients with POAG and 40 healthy age-
      and sex-matched subjects underwent three periods of isometric exercise, each
      consisting of 2 min of handgripping. Optic nerve head blood flow (ONHBF) was
      measured continuously using LDF. Systemic blood pressure, intraocular pressure
      and ocular perfusion pressure were assessed in all participants. RESULTS:
      Isometric exercise was associated with an increase in ocular perfusion pressure
      during all handgripping periods in both groups (p < 0.001). However, there was no
      change in ONHBF in either group. Three of the glaucoma patients and two of the
      healthy subjects showed a consistent 10% decrease in blood flow during isometric
      exercise, in spite of an increase in their blood pressure. This difference
      between groups was not significant (p = 0.61). Four other glaucoma subjects
      showed a consistent increase in blood flow of more than 10% during isometric
      exercise, whereas this was not seen in healthy subjects (p = 0.035). CONCLUSION:
      This study suggests that abnormal ONHBF autoregulation is more often seen in
      patients with POAG than healthy control subjects. The relationship to the
      glaucoma disease process is currently unknown and requires further investigation.

PMID- 30218497
TI  - Concise Review: Molecular Cytogenetics and Quality Control: Clinical Guardians
      for Pluripotent Stem Cells.
AB  - Now that induced pluripotent stem cell (iPSC)-based transplants have been
      performed in humans and organizations have begun producing clinical-grade iPSCs,
      it is imperative that strict quality control standards are agreed upon. This is
      essential as both ESCs and iPSCs have been shown to accumulate genomic
      aberrations during long-term culturing. These aberrations can include copy number
      variations, trisomy, amplifications of chromosomal regions, deletions of
      chromosomal regions, loss of heterozygosity, and epigenetic abnormalities.
      Moreover, although the differences between iPSCs and ESCs appear largely
      negligible when a high enough n number is used for comparison, the reprogramming
      process can generate further aberrations in iPSCs, including copy number
      variations and deletions in tumor-suppressor genes. If mutations or epigenetic
      signatures are present in parental cells, these can also be carried over into
      iPSCs. To maximize patient safety, we recommend a set of standards to be utilized
      when preparing iPSCs for clinical use. Reprogramming methods that do not involve
      genomic integration should be used. Cultured cells should be grown using feeder
      free and serum-free systems to avoid animal contamination. Karyotyping, whole
      genome sequencing, gene expression analyses, and standard sterility tests should
      all become routine quality control tests. Analysis of mitochondrial DNA
      integrity, whole-epigenome analyses, as well as single-cell genome sequencing of
      large cell populations may also prove beneficial. Furthermore, clinical-grade
      stem cells need to be produced under accepted regulatory good manufacturing
      process standards. The creation of haplobanks that provide major
      histocompatibility complex matching is also recommended to improve allogeneic
      stem cell engraftment. Stem Cells Translational Medicine 2018;7:867-875.

PMID- 30218500
TI  - A propeller-like small molecule as a novel G-quadruplex DNA binder: The study of
      fluorescent sensing property and preferential interactions with human telo21
      structure.
AB  - A new propeller-like small molecule was synthesized with three terminal amino
      side groups. The molecule was found to be a selective nucleic acid binder towards
      telo21 G-quadruplex DNA compared with other representative nucleic acids
      including single-stranded DNA (dA21), duplex DNA (ds26) and RNA. The fluorescent
      signal of the molecule upon interaction with telo21 G-quadruplex structure shows
      remarkable enhancement (Fmax /F0  = 17.9) while interaction with other nucleic
      acids shows the signal enhancement which is less than 2.1. In addition, a good
      linear relationship of binding signal correlated with the concentration of telo21
      DNA was obtained. Molecular docking study was also performed to acquire the
      binding behaviour and its interaction modes of the molecule with the structure of
      human telomeric DNA G-quadruplex. The modelling results show that the three
      conjugated terminal units (dimethylaminobenzyl groups) associated through the
      ethylene bridges with the central methylated pyridine ring formed a co-planar
      conformation upon stacking onto the G-quartets via pi-pi stacking interactions.
      This could be the key reason that the molecule shows excellent fluorescent signal
      of binding towards telo21 G-quadruplex DNA rather than other types of nucleic
      acids.

PMID- 30218502
TI  - Variations in carbon source-sink relationships in subalpine fir across
      elevational gradients.
AB  - Cold-adapted trees display acclimation in both carbon source and carbon sink
      capacity to low-temperature stress at their upper elevational range limits. Hence
      a balanced carbon source-sink capacity might be required for their persistence
      and survival at the elevational tree limits. The present study examined the
      spatial dynamics of carbon source-sink relationship in subalpine fir (Abies
      fargesii) trees along elevational gradients in the northern slope of the
      temperate region and in the southern slope of the subtropics in terms of climate
      in the Qinling Mountain range, north-central China. The results showed that non
      structural carbohydrate (NSC) concentrations in both the source and sink tissues
      increased with the increase in elevation. The ratio of carbon source-sink
      displayed a consistent decreasing trend with the increase in elevation and during
      growing season, showing that it was lowest at a ratio of 2.93 in the northern
      slope and at a ratio of 2.61 in the southern slope at the upper distribution
      elevations in the late growing season. Such variations of carbon source-sink
      ratio might be attributable to the balance between carbon source and sink
      activities, which changed seasonally across the elevational distribution range.
      We concluded that a ratio of carbon source-sink of at least 2.6 might be
      essential for subalpine fir trees to persist at their upper range limits.
      Therefore, a sufficient source-sink ratio and a balanced source-sink relationship
      might be required for subalpine fir trees to survive and develop at their upper
      elevational distribution limits.

PMID- 30218503
TI  - Review of structured light in diffuse optical imaging.
AB  - Diffuse optical imaging probes deep living tissue enabling structural,
      functional, metabolic, and molecular imaging. Recently, due to the availability
      of spatial light modulators, wide-field quantitative diffuse optical techniques
      have been implemented, which benefit greatly from structured light methodologies.
      Such implementations facilitate the quantification and characterization of depth
      resolved optical and physiological properties of thick and deep tissue at fast
      acquisition speeds. We summarize the current state of work and applications in
      the three main techniques leveraging structured light: spatial frequency-domain
      imaging, optical tomography, and single-pixel imaging. The theory, measurement,
      and analysis of spatial frequency-domain imaging are described. Then, advanced
      theories, processing, and imaging systems are summarized. Preclinical and
      clinical applications on physiological measurements for guidance and diagnosis
      are summarized. General theory and method development of tomographic approaches
      as well as applications including fluorescence molecular tomography are
      introduced. Lastly, recent developments of single-pixel imaging methodologies and
      applications are reviewed.

PMID- 30218504
TI  - Optical sampling depth in the spatial frequency domain.
AB  - We present a Monte Carlo (MC) method to determine depth-dependent probability
      distributions of photon visitation and detection for optical reflectance
      measurements performed in the spatial frequency domain (SFD). These distributions
      are formed using an MC simulation for radiative transport that utilizes a photon
      packet weighting procedure consistent with the two-dimensional spatial Fourier
      transform of the radiative transport equation. This method enables the
      development of quantitative metrics for SFD optical sampling depth in layered
      tissue and its dependence on both tissue optical properties and spatial
      frequency. We validate the computed depth-dependent probability distributions
      using SFD measurements in a layered phantom system with a highly scattering top
      layer of variable thickness supported by a highly absorbing base layer. We
      utilize our method to establish the spatial frequency-dependent optical sampling
      depth for a number of tissue types and also provide a general tool to determine
      such depths for tissues of arbitrary optical properties.

PMID- 30218505
TI  - Spatial frequency domain imaging using an analytical model for separation of
      surface and volume scattering.
AB  - A method to correct for surface scattering in spatial frequency domain imaging
      (SFDI) is presented. The use of a modified analytical solution of the radiative
      transfer equation allows calculation of the reflectance and the phase of a rough
      semi-infinite geometry so that both spatial frequency domain reflectance and
      phase can be applied for precise retrieval of the bulk optical properties and the
      surface scattering. For validation of the method, phantoms with different surface
      roughness were produced. Contrarily, with the modified theory, it was possible to
      dramatically reduce systematic errors due to surface scattering. The evaluation
      of these measurements with the state-of-the-art theory and measuring modality,
      i.e., using crossed linear polarizers, reveals large errors in the determined
      optical properties, depending on the surface roughness, of up to ~100  %  . These
      results were confirmed with SFDI measurements on a phantom that has a structured
      rough surface.

PMID- 30218506
TI  - From Mailbox to Mobile: Indian Pediatrics Goes Green...

PMID- 30218501
TI  - The clinical features, underlying immunology, and treatment of autoantibody
      mediated movement disorders.
AB  - An increasing number of movement disorders are associated with autoantibodies.
      Many of these autoantibodies target the extracellular domain of neuronal surface
      proteins and associate with highly specific phenotypes, suggesting they have
      pathogenic potential. Below, we describe the phenotypes associated with some of
      these commoner autoantibody-mediated movement disorders, and outline increasingly
      well-established mechanisms of autoantibody pathogenicity which include antigen
      downregulation and complement fixation. Despite these advances, and the
      increasingly robust evidence for improved clinical outcomes with early escalation
      of immunotherapies, the underlying cellular immunology of these conditions has
      received little attention. Therefore, here, we outline the likely roles of T
      cells and B cells in the generation of autoantibodies, and reflect on how these
      may guide both current immunotherapy regimes and our future understanding of
      precision medicine in the field. In addition, we summarise potential mechanisms
      by which these peripherally-driven immune responses may reach the central nervous
      system. We integrate this with the immunologically-relevant clinical observations
      of preceding infections, tumours and human leucocyte antigen-associations to
      provide an overview of the therapeutically-relevant underlying adaptive
      immunology in the autoantibody-mediated movement disorders. (c) 2018 The Authors.
      Movement Disorders published by Wiley Periodicals, Inc. on behalf of
      International Parkinson and Movement Disorder Society.

PMID- 30218507
TI  - Inducements by Pharmaceutical Companies: The Elephant in the Room.

PMID- 30218508
TI  - Programmatic Approaches for Nutritional Care in India: Addressing the Continuum
      of Care Perspectives.

PMID- 30218509
TI  - Bone Marrow Transplantation for Primary Immune Deficiency Disorders in India:
      Past, Present and Future.

PMID- 30218510
TI  - Neonatal Chikungunya: Spotlight on Gaps in Public Health.

PMID- 30218511
TI  - Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency Disorders:
      Experience from a Referral Center in India.
AB  - OBJECTIVE: To share experience of over 15 years in hematopoietic stem cell
      transplantation in children with primary immunodeficiency disorders. DESIGN:
      Medical record review. SETTING: A referral center for pediatric hemato
      oncological disorders. PARTICIPANTS: Children (<18 y) diagnosed to have primary
      immune deficiencies who underwent hematopoietic stem cell transplantation between
      2002 and August 2017. MAIN OUTCOME MEASURES: Disease-free survival, morbidity and
      mortality. RESULTS: 85 primary immunodeficiency disorder transplants were
      performed with engraftment noted in 80 (94%) transplants and an overall survival
      of 67%. The conditioning regimen was individualized based on the underlying
      immune defect. Mixed chimerism was noted in 20% children with 56% (9/16)
      remaining disease-free. Graft versus host disease was noted in 33 (39.2%)
      children with most seen in children with chronic granulomatous disease. Severe
      combined immune deficiency transplants were mainly complicated by infections.
      Immune cytopenias complicated Wiskott Aldrich syndrome and Hemophagocytic
      lymphohistiocytosis transplants. 29.4% (25/85) children underwent haploidentical
      transplant in our cohort with a survival of 70% in this group. Infectious
      complications were the most common cause of death. CONCLUSIONS: Primary
      immunodeficiency disorders are curable in India when transplanted in centers with
      experienced and trained pediatric transplant physicians and intensivists.

PMID- 30218512
TI  - Blinding Retinopathy of Prematurity in Western India: Characteristics of
      Children, Reasons for Late Presentation and Impact on Families.
AB  - OBJECTIVE: To ascertain why children with end-stage retinopathy of prematurity
      (ROP) become blind, and to explore the impact of blindness on families. DESIGN:
      Mixed quantitative and qualitative methods. SETTING: Tertiary-care eye hospital
      in India. PARTICIPANTS: Children with end-stage ROP and their carers.
      INTERVENTION: Cases presenting between June 2009 and July 2016 were identified
      from medical records and data extracted. Carers were contacted for missing
      information, if required. Data were analyzed to explore where failure had
      occurred in the process of screening and treatment. A subset of carers were
      selected for in-depth interviews to explore the impact of having a blind child.
      Interviews were recorded, transcribed and analyzed using a thematic framework.
      MAIN OUTCOME MEASURES: Parental perceptions. RESULTS: 66 children were included:
      median age 4.3 y (range 3 mo- 6 y), 58% boys. 74% were blind due to 'screening
      failure', which was associated with lower maternal education (P=0.03). Of the 17
      case of treatment failure (24.6%), majority (12, 70%) had aggressive posterior
      ROP. A subset of carers of 18 children (50% boys) were interviewed, mostly
      mothers. Most reported impoverishment as a result of having a blind child, and
      many reported lack of access to special education, negative attitudes of others
      and concerns about the future. CONCLUSIONS: Screening for retinopathy of
      prematurity needs to be expanded and counselling improved. Access to special
      education and rehabilitation need to be improved.

PMID- 30218513
TI  - Encephalitic presentation of Neonatal Chikungunya: A Case Series.
AB  - OBJECTIVE: To describe clinical features and early neurological outcomes in
      neonatal Chikungunya. METHODS: Clinical, pathological and radiological details of
      neonates with acute encephalitic features and typical rash, later diagnosed as
      Chikungunya, are presented. Neurodevelopmental evaluation and imaging was done at
      discharge/three months. RESULTS: Abnormal neurological examination with fever was
      typical presentation in all 13 babies with/without seizures/peri-oral rashes; 12
      had persistent neurological abnormalities at discharge. A follow-up at three
      months revealed continued neurodevelopmental deficits. Neuroimaging abnormalities
      were seen in eight out of ten cases. CONCLUSIONS: Perinatal Chikungunya should be
      considered in neonates presenting within first week with fever, encephalopathy
      and perioral rashes with/without seizures with history of maternal Chikungunya
      within last week before delivery.

PMID- 30218514
TI  - Prefeeding Oromotor Stimulation Program for Improving Oromotor Function in
      Preterm Infants - A Randomized Controlled Trial.
AB  - OBJECTIVE: To determine effect of Premature Infant Oral Motor Intervention
      program on oro-motor function and time to full independent wati spoon feeds in
      preterm infants. METHODS: 30 preterm infants between 28-32 weeks of gestation on
      full gavage feeds of 150 mL/kg/day were randomized to receive either pre-feed oro
      motor stimulation using Premature Infant Oral Motor Intervention (structured
      stimulation) or sham intervention (unstructured stimulation). RESULTS:
      Improvement in mean (SD) Neonatal Oro-Motor Assessment Scale (NOMAS) over 7 days
      from baseline was significantly higher in the study group infants as compared to
      control group (9.25 (1.73) vs 4.79 (1.52), P=0.001). Infants in the study group
      reached full independent wati spoon feeds significantly earlier than the infants
      in control group (4.0 (0.8) d; vs 6.64 (1.0) d; P=0.001). There was significant
      increase in weight gain after enrolment in infants in study group compared to
      those in control group. CONCLUSION: Oral stimulation program improves the oro
      motor skills and growth velocity in 28-32 week preterm infants. There is
      decreased transition time from gavage to full independent feeds by mouth.

PMID- 30218515
TI  - Assisted Physical Exercise and Stress in Preterm Neonates.
AB  - OBJECTIVE: To evaluate the markers of stress before and after a session of
      assisted physical exercise in infants born before 35 weeks' gestation. METHODS:
      25 infants born at 280/7 to 346/7 weeks were subjected to assisted physical
      exercise daily for about 10-15 min at one week of postnatal age or 33 weeks of
      post menstrual age, whichever was later. Primary outcome was salivary cortisol
      and secondary outcome was Premature infant pain profile (PIPP) score. Outcomes
      were measured, on day 5 (+/-1) of exercise. RESULTS: There was no difference in
      salivary cortisol between baseline and immediately after (P=0.16), at 90 min
      (P=0.6) or 120 min (P=0.7) after exercise. Salivary cortisol was lower at 30 min
      after exercise as compared to baseline (mean difference -0.08 ug/dL; 95% CI -0.16
      to -0.002; P=0.04). The median (IQR) PIPP score was significantly higher at 5 min
      into exercise (4 (3-6) vs 4 (3-5); P=0.04) and at completion of exercise 6 (4-8)
      vs 4 (3-5); P<0.01), as compared to baseline. CONCLUSION: Assisted physical
      exercise does not seem to result in stress in premature infants.

PMID- 30218516
TI  - Association of Undernutrition and Early Childhood Dental Caries.
AB  - OBJECTIVE: To determine the association between early childhood caries and
      nutritional status in preschool children. METHODS: Cross-sectional study among
      preschool children (N=550, age 8-60 mo) were selected in tribal, rural and urban
      health care units of Kerala. An oral examination for early childhood caries
      status was done using Deft index. The anthropometric measurements were recorded.
      Multiple logistic regression with other covariates was used to determine the
      association between the early childhood caries and nutritional status. RESULTS:
      The mean (SD) Deft scores were 0.93 (1.73), 2.22 (2.92) and 3.40 (3.23) for
      children with normal nutritional status, borderline undernutrition and
      undernutrition, respectively. Children with borderline undernutrition (adjusted
      OR 2.05, 95% CI 1.20, 3.49) or undernutrition (adjusted OR 3.46, 95% CI 1.93,
      6.29) had higher odds of dental caries in comparison to those with normal
      nutritional status. CONCLUSION: Undernutrition is associated with early childhood
      caries among preschool children.

PMID- 30218517
TI  - Mobile Phone Technology Based Incentives to Enhance Routine Childhood
      Immunization: Evidence-based Medicine Viewpoint.

PMID- 30218518
TI  - Mobile Phone Technology Based Incentives to Enhance Routine Childhood
      Immunization: Pediatrician's Viewpoint.

PMID- 30218519
TI  - Mobile Phone Technology Based Incentives to Enhance Routine Childhood
      Immunization: Medical Information Technologist's Viewpoint.

PMID- 30218520
TI  - An Infant with Respiratory Distress and Loose Stools.
AB  - We present the case of a 3-month-old girl who was admitted with complaints of
      loose stools and respiratory distress. She also had a history of rash and
      alopecia. Laboratory investigations revealed lymphopenia with reduced
      immunoglobulin G and immunoglobulin A. Lymphocyte subset analysis by flow
      cytometry revealed T-B+NK+ severe combined immunodeficiency (SCID). She died due
      to severe pneumonia, shock and pulmonary hemorrhage. Autopsy findings revealed
      disseminated cytomegalovirus infection in the lung, liver, adrenals and heart.
      Thymus was found to be dysplastic and showed characteristic histopathologic
      features of SCID.

PMID- 30218521
TI  - Pulmonary Metastasis in Infantile Choriocarcinoma: Successful Outcome.
AB  - BACKGROUND: Infantile choriocarcinoma is usually fatal without appropriate
      treatment. CASE CHARACTERISTICS: A 3-month-old boy who presented with respiratory
      distress, hepatomegaly, amemia and bilateral nodular lesions on chest X-ray.
      OBSERVATION: Fine-needle liver aspiration revealed necrotic tumour cells. The
      serum b-hCG level was very high (2057 mIU/L), supporting a diagnosis of infantile
      choriocarcinoma of the liver. Surgical resection after cisplatin-based multiagent
      chemotherapy afforded successful remission. MESSAGE: Early treatment of infantile
      choriocarcinoma can yield a successful outcome.

PMID- 30218522
TI  - Nebulized N-Acetylcysteine for Management of Plastic Bronchitis.
AB  - BACKGROUND: Plastic bronchitis is characterized by formation of extensive
      obstructive endobronchial casts and high recurrence rates. CASE CHARACTERISTICS:
      Two children (1-year-old girl, 7-year-old boy) who had recurrent episodes of
      respiratory distress with acute worsening. Bronchoscopy revealed membrane-like
      casts. Both children were managed with nebulized N-acetylcysteine in addition to
      management for asthma. OUTCOME: Symptom-free without recurrence for more than 9
      months of follow-up. MESSAGE: Nebulized N- acetylcysteine may be helpful in
      prevention of recurrence of plastic bronchitis due to asthma.

PMID- 30218524
TI  - AEFI Surveillance - The Learning Curve Continues.

PMID- 30218523
TI  - A Unique Genomic Variant of HDR Syndrome in Newborn.
AB  - BACKGROUND: HDR syndrome (also known as Barakat syndrome) is a rare genetic
      disorder due to deletions/mutations on specific regions of zinc-finger
      transcription factor (GATA3) gene. CASE CHARACTERISTICS: A male preterm infant
      presented with multiple dysmorphic features characterized by small for
      gestational age, hypognathia and facial abnormalities. OBSERVATION:
      Investigations revealed hypocalcemia and low parathyroid hormone levels and
      bilateral sensorineural deafness. OUTCOME: Chromosomal microarray analysis
      revealed a combination of deletion on chromosome 10p (10p15.3p14) with loss of
      GATA3 gene and duplication of chromosome 20p (20p13p12.3) as a result of
      unbalanced 10:20 translocation. MESSAGE: Detecting this syndrome at neonatal age
      is very important because it allows early intervention to minimize future
      clinical problems.

PMID- 30218525
TI  - Severe Bradycardia and Hypotension Possibly Induced by Ranitidine.

PMID- 30218526
TI  - Subacute Sclerosing Panencephalitis: A Disease Not to be Forgotten.

PMID- 30218527
TI  - Galactomannan Antigen Test for Invasive Aspergillus Infection in Febrile
      Neutropenic Children.

PMID- 30218528
TI  - Galactomannan Antigen Test for Invasive Aspergillus Infection in Febrile
      Neutropenic Children: Author's Reply.

PMID- 30218529
TI  - Therapeutic Hypothermia using Phase changing Material in Indian Neonates.

PMID- 30218530
TI  - Therapeutic Hypothermia using Phase changing Material in Indian Neonates:
      Authors' Reply.

PMID- 30218531
TI  - Actinic Lichen Planus.

PMID- 30218533
TI  - Stress survival islet 1 contributes to serotype-specific differences in biofilm
      formation in Listeria monocytogenes.
AB  - Listeria monocytogenes has a significant impact on the food industry by forming
      biofilms on food-processing equipment. Tandem analysis of whole-genome sequencing
      data with biofilm data from 166 environmental and food-related L. monocytogenes
      isolates has revealed serotypic and genetic factors that strongly correlate with
      adherence and biofilm formation, such as lineage, plasmid harbourage, a three
      codon deletion in inlA and the presence of the stress survival islet 1 (SSI-1).
      Strains from serotype 1/2b, the majority of which contained SSI-1, formed the
      strongest biofilms, while serotype 4b strains, the majority of which did not
      contain SSI-1, formed the weakest biofilms. When serotype 1/2a was separated by
      its SSI-1 genotype, SSI-1-positive 1/2a strains demonstrated significantly higher
      capacity for biofilm formation after 3 days of growth at 30 degrees C (P <
      0.0001). Together, these findings indicate that SSI-1 may contribute to serotype
      associated differences in the biofilm-forming capacity in L. monocytogenes.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Parallel analysis of whole-genome sequences
      and serotype-specific data was performed to identify genetic markers that
      correlate with increased adherence and biofilm formation in L. monocytogenes. The
      analyses revealed the hitherto unrecognized role of SSI-1 in biofilm formation,
      contributing to deeper understanding of genetic factors that influence behaviour
      of the species in the food processing environment..

PMID- 30218532
TI  - Factors Associated with Caregiver Burden in Primary Caregivers of Patients with
      Adolescent Scoliosis: A Descriptive Cross-Sectional Study.
AB  - BACKGROUND Primary caregivers for patients with scoliosis suffer from
      considerable distress and burden. However, a few studies have examined the
      factors related to burden of caregivers of patients with adolescent scoliosis,
      particularly in China. Therefore, the present study aimed to identify patient and
      caregiver characteristics associated with caregiver burden. MATERIAL AND METHODS
      A cross-sectional study was conducted in a sample comprising 87 pairs of patients
      with adolescent scoliosis and their primary caregivers from July 2014 to October
      2016 in Xi'an, China. Patients and their primary caregivers were administered a
      sociodemographic questionnaire. The caregiver burden, social support, and self
      efficacy were assessed using the Chinese version of the Zarit Burden Interview
      (ZBI), Social Support Rating Scale (SSRS), and General Self-Efficacy Scale (GSE).
      A multivariate analysis was used to evaluate the factors associated with
      caregiver burden. RESULTS Most primary caregivers observed in this study were
      female (65.5%), with mothers of the patients accounting for 58.6% of all the
      caregivers. The ZBI score of primary caregivers was 36.83+/-13.30, and most
      caregivers (88.5%) had moderate or severe burden. The factors associated with
      caregiver burden were Cobb angle of patients, SSRS scores, GSE scores, and
      monthly household income per capita of the caregiver (R2=0.556; P<0.001). The
      identified significant factors explained nearly 56% of the variance in the
      caregiver burden. CONCLUSIONS The data indicated that most primary caregivers for
      patients with scoliosis had a considerable caregiver burden, and intervention of
      social support and self-efficacy might be helpful in reducing caregiver burden.

PMID- 30218534
TI  - Gold-Clip-Assisted Self-Assembly and Proton-Coupled Expansion-Contraction of a
      Cofacial FeIII -Porphyrin Cage.
AB  - A molecular cage {Au8 (MU-PAnP)4 [Fe(H2 O)2 (TPyP)]2 (OTf)2 }(OTf)8 (1) composed
      of two cofacial FeIII -porphyrin can be self-assembled from the gold clip [Au2
      (PAnP)Cl2 ] and Fe3+ (H2 O)2 (TPyP)+ (PAnP=9,10-bis(diphenylphosphino)anthracene,
      TPyP=meso-tetra(4-pyridyl)porphyrinato). The height of the cage is 8.579(3) A.
      The addition of a base to a solution of the cage leads to a contracted and
      twisted cage {[Au8 (MU-PAnP)4 [Fe2 (MU-O)(TPyP)2 ]}(OTf)8 (2), which has a height
      of ~4.4 A and porphyrin-porphyrin torsional angle of ~20 degrees . The contracted
      cage can be synthesized independently from the gold clip and Fe2 (MU-O)(TPyP)2 .
      The spectroscopy and crystal structure of an unclipped analog of the contracted
      cage, {[AuPPh3 )8 [Fe2 (MU-O)(TPyP)2 ]}(OTf)8 (3), supports the DFT-calculated
      structure of 2. NMR and UV/Vis titrations show that the expansion-untwisting and
      contraction-twisting of the cage is reversible.

PMID- 30218535
TI  - Arabidopsis UBC13 differentially regulates two programmed cell death pathways in
      responses to pathogen and low-temperature stress.
AB  - UBC13 is required for Lys63-linked polyubiquitination and innate immune responses
      in mammals, but its functions in plant immunity remain to be defined. Here we
      used genetic and pathological methods to evaluate roles of Arabidopsis UBC13 in
      response to pathogens and environmental stresses. Loss of UBC13 failed to
      activate the expression of numerous cold-responsive genes and resulted in
      hypersensitivity to low-temperature stress, indicating that UBC13 is involved in
      plant response to low-temperature stress. Furthermore, the ubc13 mutant displayed
      low-temperature-induced and salicylic acid-dependent lesion mimic phenotypes.
      Unlike typical lesion mimic mutants, ubc13 did not enhance disease resistance
      against virulent bacterial and fungal pathogens, but diminished hypersensitive
      response and compromised effector-triggered immunity against avirulent bacterial
      pathogens. UBC13 differently regulates two types of programmed cell death in
      response to low temperature and pathogen. The lesion mimic phenotype in the ubc13
      mutant is partially dependent on SNC1. UBC13 interacts with an F-box protein CPR1
      that regulates the homeostasis of SNC1. However, the SNC1 protein level was not
      altered in the ubc13 mutant, implying that UBC13 is not involved in CPR1
      regulated SNC1 protein degradation. Taken together, our results revealed that
      UBC13 is a key regulator in plant response to low temperature and pathogens.

PMID- 30218536
TI  - The human yolk sac size reflects involvement in embryonic and fetal growth
      regulation.
AB  - INTRODUCTION: The human yolk sac provides the embryo with stem cells, nutrients,
      and gas exchange. We hypothesized that more maternal resources, reflected in body
      size and body composition, would condition a a larger yolk sac, ensuring
      resources for the growing embryo. Thus, we aimed to determine the relation
      between maternal size in early pregnancy and yolk sac size. MATERIAL AND METHODS:
      This subsidiary study was embedded in the multinational World Health Organization
      fetal growth project that included healthy women with a body mass index of 18-30,
      reliable information of their regular last menstrual period and singleton
      pregnancies. Yolk sac diameter, crown-rump length, and maternal height, weight,
      body mass index, and body composition were assessed before 13 weeks of gestation,
      and the fetal biometry was repeated during the pregnancy. RESULTS: Of 140
      participants, 122 with a successful yolk sac measurement were entered in the
      present analysis. Maternal weight was negatively associated with the yolk sac
      diameter (P = 0.007) and so was maternal height (P = 0.011), fat mass (P =
      0.037), and lean body mass (P = 0.018), but not body mass index (P = 0.121).
      Significant effects were predominantly due to the female embryos and could be
      traced at 24 weeks of gestation. That is, a small yolk sac : crown-rump length
      ratio in early pregnancy was associated with a high fetal abdominal circumference
      (P < 0.001) and estimated fetal weight (P = 0.001). CONCLUSIONS: The human yolk
      sac is involved in the regulation of embryonic growth, but contrary to our
      hypothesis, the yolk sac has a compensatory capacity, being larger when the
      mothers are smaller; and the effect can be traced on fetal size at 24 weeks of
      gestation.

PMID- 30218537
TI  - NADPH oxidase activity is required for ER stress survival in plants.
AB  - In all eukaryotes, the unfolded protein response (UPR) relieves endoplasmic
      reticulum (ER) stress, which is a potentially lethal condition caused by the
      accumulation of misfolded proteins in the ER. In mammalian and yeast cells,
      reactive oxygen species (ROS) generated during ER stress attenuate the UPR,
      negatively impacting cell survival. In plants, the relationship between the UPR
      and ROS is less clear. Although ROS develop during ER stress, the sources of ROS
      linked to ER stress responses and the physiological impact of ROS generation on
      the survival from proteotoxic stress are yet unknown. Here we show that in
      Arabidopsis thaliana the respiratory burst oxidase homologs, RBOHD and RBOHF,
      contribute to the production of ROS during ER stress. We also demonstrate that
      during ER stress RBOHD and RBOHF are necessary to properly mount the adaptive UPR
      and overcome temporary and chronic ER stress situations. These results ascribe a
      cytoprotective role to RBOH-generated ROS in the defense from proteotoxic stress
      in an essential organelle, and support a plant-specific feature of the UPR
      management among eukaryotes.

PMID- 30218539
TI  - Isolation and characterization of an exopolysaccharide-producing Leuconostoc
      citreum strain from artisanal cheese.
AB  - High molar mass exopolysaccharides (EPS) produced from sucrose by lactic acid
      bacteria (LAB) are of great interest as natural additives to use in foods,
      medical and pharmaceutical industry. This study aimed to identify the EPS
      produced by Leuconostoc citreum L3C1E7 isolated from Pico cheese and characterize
      the strain for technological and probiotic potential. Purified EPS was isolated
      from the culture of L. citreum L3C1E7 by ethanol precipitation, with a yield of
      520 mg ml-1 . The EPS-producing strain had a mucoid phenotype and average
      molecular weight of 5.88 * 106  Da. The structural characterization of the
      purified EPS was determined by 1 H, 13 C and two-dimensional NMR spectroscopy.
      EPS was composed of alternating alpha-(1->6)-linked and alpha-(1->3)-linked D
      glucopyranyl units, suggesting the existence of an alternan. The strain was slow
      acidifying, produced diacetyl and displayed high esterase/lipase and
      aminopeptidase activities, which promote the desirable flavours in dairy
      products. Moreover, L. citreum showed moderate resistance to the adverse
      conditions of the gastrointestinal (GI) tract and high adhesion to GI cells. This
      work provides a better understanding of EPS produced by L. citreum and the
      potential application of EPS-producing strain in food and/or as a probiotic
      culture. SIGNIFICANCE AND IMPACT OF THE STUDY: Some LAB strains are known to use
      extracellular glycoside-hydrolase enzymes for synthesizing a diversity of
      exopolysaccharides (EPS) with potential application as natural additives to
      foods. Previous studies have identified an EPS-producing Leuconostoc citreum
      strain with immunomodulatory properties. This work provides a better
      understanding of EPS produced by this strain and the potential application of the
      strain in food fermentation and/or as a probiotic culture.

PMID- 30218538
TI  - Comparing optimal and empirical stomatal conductance models for application in
      Earth system models.
AB  - Earth system models (ESMs) rely on the calculation of canopy conductance in land
      surface models (LSMs) to quantify the partitioning of land surface energy, water,
      and CO2 fluxes. This is achieved by scaling stomatal conductance, gw , determined
      from physiological models developed for leaves. Traditionally, models for gw have
      been semi-empirical, combining physiological functions with empirically
      determined calibration constants. More recently, optimization theory has been
      applied to model gw in LSMs under the premise that it has a stronger grounding in
      physiological theory and might ultimately lead to improved predictive accuracy.
      However, this premise has not been thoroughly tested. Using original field data
      from contrasting forest systems, we compare a widely used empirical type and a
      more recently developed optimization-type gw model, termed BB and MED,
      respectively. Overall, we find no difference between the two models when used to
      simulate gw from photosynthesis data, or leaf gas exchange from a coupled
      photosynthesis-conductance model, or gross primary productivity and
      evapotranspiration for a FLUXNET tower site with the CLM5 community LSM. Field
      measurements reveal that the key fitted parameters for BB and MED, g1B and g1M,
      exhibit strong species specificity in magnitude and sensitivity to CO2 , and CLM5
      simulations reveal that failure to include this sensitivity can result in
      significant overestimates of evapotranspiration for high-CO2 scenarios. Further,
      we show that g1B and g1M can be determined from mean ci /ca (ratio of leaf
      intercellular to ambient CO2 concentration). Applying this relationship with ci
      /ca values derived from a leaf delta13 C database, we obtain a global
      distribution of g1B and g1M , and these values correlate significantly with mean
      annual precipitation. This provides a new methodology for global parameterization
      of the BB and MED models in LSMs, tied directly to leaf physiology but
      unconstrained by spatial boundaries separating designated biomes or plant
      functional types.

PMID- 30218540
TI  - A novel augmented reality (AR) scheme for knee replacement surgery by considering
      cutting error accuracy.
AB  - BACKGROUND: Augmented reality (AR) surgery has not been successfully implemented
      in knee replacement surgery due to the negative effect of cutting errors. This
      research aims to decrease the cutting error to reduce the chronic pain after knee
      replacement. METHODOLOGY: The proposed system consists of a volume subtraction
      technique that considers the history of the area that has been cut and measures
      it against the target shape. RESULTS: Results minimized the cutting error by
      about 1 mm. Therefore, it provides a significant video accuracy improvement in
      alignment to 0.40 to 0.55 mm from 0.55 to 0.64 and a decrease in processing time
      from 12 to 13 fs/s to 9 to10 fs/s. CONCLUSION: The proposed system is focused on
      overlaying only the remaining areas of surgery that need to be completed.
      Finally, this study solves the issues of navigation with AR when cutting bones in
      a scheduled direction and depth.

PMID- 30218541
TI  - Impact of clone size with a single cytogenetic abnormality on the revised
      International Prognostic Scoring System in myelodysplastic syndromes.

PMID- 30218542
TI  - A pair of phospho-base methyltransferases important for phosphatidylcholine
      biosynthesis in Arabidopsis.
AB  - Phosphatidylcholine (PtdCho) is a predominant membrane lipid class in eukaryotes.
      Phospho-base N-methyltransferase (PMT) catalyzes a critical step in PtdCho
      biosynthesis. However, in Arabidopsis thaliana, the discovery of involvement of
      the specific PMT isoform in PtdCho biosynthesis remains elusive. Here, we show
      that PMT1 and PMT3 redundantly play an essential role in phosphocholine (PCho)
      biosynthesis, a prerequisite for PtdCho production. A pmt1 pmt3 double mutant was
      devoid of PCho, which affected PtdCho biosynthesis in vivo, showing severe growth
      defects in post-embryonic development. PMT1 and PMT3 were both highly expressed
      in the vasculature. The pmt1 pmt3 mutants had specifically affected leaf vein
      development and showed pale-green seedlings that were rescued by exogenous
      supplementation of PCho. We suggest that PMT1 and PMT3 are the primary enzymes
      for PCho biosynthesis and are involved in PtdCho biosynthesis and vascular
      development in Arabidopsis seedlings.

PMID- 30218543
TI  - A small-sample kernel association test for correlated data with application to
      microbiome association studies.
AB  - Recent research has highlighted the importance of the human microbiome in many
      human disease and health conditions. Most current microbiome association analyses
      focus on unrelated samples; such methods are not appropriate for analysis of data
      collected from more advanced study designs such as longitudinal and pedigree
      studies, where outcomes can be correlated. Ignoring such correlations can
      sometimes lead to suboptimal results or even possibly biased conclusions. Thus,
      new methods to handle correlated outcome data in microbiome association studies
      are needed. In this paper, we propose the correlated sequence kernel association
      test (CSKAT) to address such correlations using the linear mixed model.
      Specifically, random effects are used to account for the outcome correlations and
      a variance component test is used to examine the microbiome effect. Compared to
      existing genetic association tests for longitudinal and family samples, we
      implement a correction procedure to better calibrate the null distribution of the
      score test statistic to accommodate the small sample size nature of data
      collected from a typical microbiome study. Comprehensive simulation studies are
      conducted to demonstrate the validity and efficiency of our method, and we show
      that CSKAT achieves a higher power than existing methods while correctly
      controlling the Type I error rate. We also apply our method to a microbiome data
      set collected from a UK twin study to illustrate its potential usefulness. A free
      implementation of our method in R software is available at
      https://github.com/jchen1981/SSKAT.

PMID- 30218544
TI  - Linking permafrost thaw to shifting biogeochemistry and food web resources in an
      arctic river.
AB  - Rapidly, increasing air temperatures across the Arctic are thawing permafrost and
      exposing vast quantities of organic carbon, nitrogen, and phosphorus to microbial
      processing. Shifts in the absolute and relative supplies of these elements will
      likely alter patterns of ecosystem productivity and change the way carbon and
      nutrients are delivered from upland areas to surface waters such as rivers and
      lakes. The ultra-oligotrophic nature of surface waters across the Arctic renders
      these ecosystems particularly susceptible to changes in productivity and food web
      dynamics as permafrost thaw alters terrestrial-aquatic linkages. The objectives
      of this study were to evaluate decadal-scale patterns in surface water chemistry
      and assess potential implications of changing water chemistry to benthic organic
      matter and aquatic food webs. Data were collected from the upper Kuparuk River on
      the North Slope of Alaska by the U.S. National Science Foundation's Long-Term
      Ecological Research program during 1978-2014. Analyses of these data show
      increases in stream water alkalinity and cation concentrations consistent with
      signatures of permafrost thaw. Changes are also documented for discharge
      corrected nitrate concentrations (+), discharge-corrected dissolved organic
      carbon concentrations (-), total phosphorus concentrations (-), and delta13 C
      isotope values of aquatic invertebrate consumers (-). These changes show that
      warming temperatures and thawing permafrost in the upland environment are leading
      to shifts in the supply of carbon and nutrients available to surface waters and
      consequently changing resources that support aquatic food webs. This demonstrates
      that physical, geochemical, and biological changes associated with warming
      permafrost are fundamentally altering linkages between upland and aquatic
      ecosystems in rapidly changing arctic environments.

PMID- 30218545
TI  - Sequestration of artemin reduces inflammation-induced activation and
      sensitization of bone marrow nociceptors in a rodent model of carrageenan-induced
      inflammatory bone pain.
AB  - BACKGROUND: Pathologies that affect the bone marrow have a significant
      inflammatory component; however, it is not clear how inflammatory mediators
      affect nociceptive nerve terminals within the marrow cavity. METHODS: In this
      study, an in vivo bone-nerve preparation was used to directly record the
      physiological response properties of bone marrow nociceptors innervating the
      tibial marrow cavity of rats, before and after application of the inflammatory
      agent carrageenan. In addition, endogenous artemin was sequestered by application
      of an artemin neutralizing antibody to determine if this could prevent the
      inflammation-induced physiological changes observed. RESULTS: A single injection
      of carrageenan administered into the tibial marrow cavity produced rapid changes
      in weight bearing (pain-like behaviour) in conscious animals. Carrageenan, but
      not saline, activated bone marrow nociceptors in whole-nerve recordings and
      sensitized a subtype of Adelta-bone marrow nociceptors to mechanical stimulation.
      The activation and sensitization had a rapid time course that matched that of
      pain-like behaviours. Sequestration of endogenous artemin significantly reduced
      carrageenan-induced increases in ongoing activity and completely abolished
      sensitization of bone marrow nociceptors to mechanical stimulation. CONCLUSIONS:
      These observations indicate that inflammation affects the activity and
      sensitivity of bone marrow nociceptors; that artemin plays a role in these
      changes; and that artemin might be a promising target for pharmacological
      manipulations in the treatment of inflammatory bone pain. SIGNIFICANCE: Most
      pathologies that affect the bone marrow have an inflammatory component. We have
      used a model of carrageenan-induced inflammation to show that sequestration of
      artemin reduces inflammation-induced activation and sensitization of bone marrow
      nociceptors. Our findings suggest that artemin signalling is a target for the
      treatment of inflammatory bone pain.

PMID- 30218546
TI  - Temperature niche position and breadth of ectomycorrhizal fungi: Reduced
      diversity under warming predicted by a nested community structure.
AB  - Species with narrow niche breadths are assumed to be more susceptible to
      environmental changes than those with wide niche breadths. Although information
      on niche properties is necessary for predicting biological responses to
      environmental changes, such information is largely missing for soil microbes. In
      this study, we present the temperature niche positions and breadths of a
      functionally important group of eukaryotic soil microbes, ectomycorrhizal (EM)
      fungi. We compiled high-quality EM fungal sequence data from 26 forested sites in
      Japan (with mean annual temperatures ranging from 1.6 to 23.6 degrees C) to
      create temperature niche profiles for each individual fungal species. Nested
      theory and a newly developed weighted-randomization null model were applied to 75
      fungal operational taxonomic units (OTUs) with high occurrence records to examine
      potential preferences for certain temperature positions and breadths. Our
      analyses revealed that (a) many EM fungal OTUs were restricted to habitats with
      low mean annual temperatures, (b) fungal OTUs observed at colder sites exhibited
      narrower temperature breadths than expected by chance, (c) the composition of EM
      fungal OTUs exhibited a nested pattern along the temperature gradient, and (d) EM
      fungal richness was highest at colder sites, where the greatest degree of overlap
      in OTU occurrence was observed. These findings imply that future warming may
      limit the distribution of many EM fungal species that are currently adapted to
      only cold climates. This could eventually reduce EM fungal biodiversity, which is
      linked to forest function through symbiotic associations with trees. This study
      demonstrates the distribution and environmental ranges of various EM fungal
      species and can contribute to develop species distribution models with the aim of
      conserving microbes in the face of climate change.

PMID- 30218547
TI  - Attenuation of murine allergic airway inflammation with a CXCR1/CXCR2 chemokine
      receptor inhibitor.

PMID- 30218548
TI  - Overlooked climate parameters best predict flowering onset: Assessing
      phenological models using the elastic net.
AB  - Determining the manner in which plant species shift their flowering times in
      response to climatic conditions is essential to understanding and forecasting the
      impacts of climate change on the world's flora. The limited taxonomic diversity
      and duration of most phenological datasets, however, have impeded a
      comprehensive, systematic determination of the best predictors of flowering
      phenology. Additionally, many studies of the relationship between climate
      conditions and plant phenology have included only a limited set of climate
      parameters that are often chosen a priori and may therefore overlook those
      parameters to which plants are most phenologically sensitive. This study
      harnesses 894,392 digital herbarium records and 1,959 in situ observations to
      produce the first assessment of the effects of a large number (25) of climate
      parameters on the flowering time of a very large number (2,468) of angiosperm
      taxa throughout North America. In addition, we compare the predictive capacity of
      phenological models constructed from the collection dates of herbarium specimens
      vs. repeated in situ observations of individual plants using a regression
      approach-elastic net regularization-that has not previously been used in
      phenological modeling, but exhibits several advantages over ordinary least
      squares and stepwise regression. When herbarium-derived data and in situ
      phenological observations were used to predict flowering onset, the multivariate
      models based on each of these data sources had similar predictive capacity (R2  =
      0.27). Further, apart from mean maximum temperature (TMAX), the two best
      predictors of flowering time have not commonly been included in phenological
      models: the number of frost-free days (NFFD) and the quantity of precipitation as
      snow (PAS) in the seasons preceding flowering. By vetting these models across an
      unprecedented number of taxa, this work demonstrates a new approach to
      phenological modeling.

PMID- 30218549
TI  - Bisphenol A affects neural development of the ascidian Ciona robusta.
AB  - Bisphenol A (BPA) is an organic pollutant derived from plastic degradation that
      has numerous and variable adverse effects on human health and wildlife. In
      particular, it has been reported that BPA can alter reproductive processes and
      nervous system development in vertebrates. Considering BPA presence in marine
      environment and the scant data available on its interaction with nervous system
      development, we analyzed the effect of BPA exposure on sperm viability,
      fertilization, embryogenesis, and neural differentiation of the ascidian Ciona
      robusta. Ascidians are members of the Phylum Tunicata, the sister group of
      Vertebrata, sharing with them fundamental developmental processes. Our results
      showed that first cell division was altered starting from 5 uM concentration.
      Lethal concentration (LC 50 ) was estimated to be 5.2 uM. Larvae developed from
      treated embryos showed specific malformations to the pigment cells even at 0.1
      uM, corresponding to the highest environmental concentration reported so far.
      Moreover, GABAergic and dopaminergic neurons proved to be target organs of BPA
      teratogenic action, in accordance with similar results reported in vertebrate
      animal models. Overall, our results suggest that BPA can exert its effects on
      nervous system acting on different pathways and underline that C. robusta is a
      valuable invertebrate animal model for preliminary screenings of effects of
      pollutants on vertebrates.

PMID- 30218550
TI  - Effect of glucocorticoids on androgen biosynthesis in the testes of the toad
      Rhinella arenarum (Amphibia, Anura).
AB  - In rat Leydig cells, glucocorticoids (GCs) inhibit testosterone production
      through the interaction with the glucocorticoid receptor (GR). However, the
      sensitivity of those cells to GCs is regulated by the enzyme 11beta
      hydroxysteroid dehydrogenase Type 1 (11beta-HSD1). In the testes of the toad
      Rhinella arenarum, the presence of an 11beta-HSD similar to type 2 and a
      cytosolic GR has also been described. However, there is a lack of information
      regarding the effects of GCs on amphibian testicular steroidogenesis. In this
      study, the effects of corticosterone on androgen production, and the activity of
      two steroidogenic enzymes in toad testes were reported. Corticosterone inhibits
      androgen production via the GR because the GR antagonist RU486 prevents
      corticosterone-induced inhibition of testosterone. Corticosterone also reduced
      the activity of the cytochrome P450 17-hydroxylase, C17,20-lyase (Cyp450 c17 )
      without affecting the 3beta-hydroxysteroid dehydrogenase/isomerase activity. This
      effect on Cyp450 c17 was likewise inhibited by RU486. On the other hand,
      corticosterone had no effect on the amount of steroidogenic acute regulator
      protein. These results suggest that GCs inhibit steroidogenesis in toad testes by
      reducing of Cyp450 c17 activity via a GR-mediated mechanism.

PMID- 30218551
TI  - Hierarchical Cobalt Borate/MXenes Hybrid with Extraordinary Electrocatalytic
      Performance in Oxygen Evolution Reaction.
AB  - Oxygen evolution reaction (OER) is a key reaction for many renewable energy
      storage and conversion techniques. Developing efficient non-precious metal-based
      electrocatalysts for OER has attracted increasing attention. Herein is reported a
      strategy to fabricate hierarchical cobalt borate/Ti3 C2 Tx MXene (Co-Bi /Ti3 C2
      Tx ) hybrid through fast chemical reactions at room temperature. This interesting
      hierarchical structure of Co-Bi /Ti3 C2 Tx hybrid is beneficial for exposing more
      active sites, improving mass diffusion, and charge-transfer pathways for
      electrochemical reaction. Moreover, a strong interaction between Co-Bi and Ti3 C2
      Tx ensures efficient charge transfer and facilitates the electrostatic attraction
      of more anionic intermediates for a fast redox process. Consequently, the
      hierarchical Co-Bi /Ti3 C2 Tx hybrid shows extraordinary OER catalytic activity
      to deliver a current density of 10 mA cm-2 at an overpotential of 250 mV, and a
      Tafel slope of about 53 mV dec-1 .

PMID- 30218552
TI  - Development of a highly accurate and sensitive diagnostic tool for pyrethroid
      resistant chimeric P450 CYP337B3 of Helicoverpa armigera using loop-mediated
      isothermal amplification.
AB  - Recent studies have shown that pyrethroid resistance in the cotton bollworm (CBW)
      Helicoverpa armigera is conferred by the generation of a chimeric CYP337B3 gene,
      which resulted from unequal crossing-over between the CYP337B1 and CYP337B2
      genes. In this study, we developed a diagnostic protocol based on the loop
      mediated isothermal amplification (LAMP) assay for the detection of chimeric
      CYP337B3. The CYP337B3 LAMP assay utilized six primers and generated strong
      fluorescence signals visible to the naked eye under normal or ultraviolet light.
      The primers were designed based on CYP337B3v1 (JQ995292), the major allele
      detected in Australia. The detection limit of this LAMP assay was 10 fg genomic
      DNA in a 25-ul reaction mixture. Compared with CYP337B2v1, the Korean CYP337B3v2
      allele had two nucleotide mismatches within the amplifying regions of this LAMP
      assay; therefore, we confirmed that polymerase chain reaction-synthesized
      CYP337B3v2 was well amplified using this LAMP assay. In addition, we determined
      that the presence of CYP337B3 from H. armigera collected by pheromone traps from
      Korean fields could be confirmed using this LAMP assay. This assay could detect
      CYP337B3 even in heterozygotes, which is relevant because CYP337B3 is dominant,
      and heterozygotes are pyrethroid resistant. Therefore, the newly developed
      CYP337B3 LAMP assay could detect the presence of pyrethroid resistance in H.
      armigera that were captured by pheromone traps during the early season and
      provide information on whether pyrethroids could be used to control H. armigera.

PMID- 30218553
TI  - Patterns of Screen Time Among Rural Mexican-American Children on the New Mexico
      Mexico Border.
AB  - INTRODUCTION: The prevalence of obesity is 26% among Hispanic children and
      teenagers and 47% among Hispanic adults. One contributor to obesity is sedentary
      behavior, such as using electronic screen devices (ie, screens). Low-income and
      Hispanic youths spend more time using such devices than other youths. METHODS: We
      interviewed 202 parents of Mexican-origin children aged 6 to 10 years in 2 rural
      communities near the US-Mexico border to determine screen use among children. We
      tested for associations between covariates and heavy screen use (>=4 hours/day)
      and calculated adjusted odds ratios (AORs) to identify independent, modifiable
      risk factors for such use. RESULTS: More than two-thirds (68.3%) of households
      had an annual income of less than $24,000, 89.1% spoke primarily Spanish, and
      92.1% had internet access. The percentage of children with heavy screen use was
      14.9% on weekdays and 25.2% on weekends. Smartphones were used by 62.4% of
      children, desktops or laptops by 60.9%; homework was the most common reason for
      use of these devices. One in 3 children used them for social media. Increased
      odds of heavy screen use were associated with having a television on while the
      child ate (weekday AOR = 3.02; 95% confidence interval [CI], 1.08-8.45 and
      weekend AOR = 2.38; 95% CI, 1.04-5.40) and using electronics to entertain
      (weekend AOR = 2.94; 95% CI, 1.15-7.51). More than 3 family meals per week (AOR =
      0.40; 95% CI, 0.17-0.94 compared with <=3 meals) and 2 or 3 family activities per
      week (AOR = 0.33; 95% CI, 0.12-0.87 compared with <=1 activity) were associated
      with decreased odds of heavy weekend use. CONCLUSION: Even in low-income, Spanish
      speaking communities, children have access to electronic devices, social media,
      and the internet, and a substantial fraction of them are heavy users. Efforts to
      reduce screen time might focus on understanding and changing the social norms
      that promote it.

PMID- 30218554
TI  - Visualizing Reach of Racial and Ethnic Approaches to Community Health for Asian
      Americans: the REACH FAR Project in New York and New Jersey.

PMID- 30218555
TI  - Outcomes With Drug-Coated Balloons for Treating the Side Branch of Coronary
      Bifurcation Lesions.
AB  - BACKGROUND: Treating coronary bifurcations remains limited by technical
      difficulties and suboptimal long-term outcomes, often affecting the side branch
      (SB). Drug-coated balloon (DCB) in SB treatment could reduce neointimal
      hyperplasia and the risk for restenosis. METHODS: We performed a systematic
      review of all studies published between January 2000 and February 2018 reporting
      the outcomes of DCB vs non-coated balloon angioplasty (BA) in the treatment of
      the SB in coronary bifurcation lesions. Outcomes included SB late lumen loss, SB
      binary restenosis, target-lesion revascularization (TLR), and major adverse
      cardiac event (MACE) rate. RESULTS: Four studies with 349 patients were included
      in the meta-analysis (three randomized controlled trials [RCTs] and one
      observational study). SB stenting was performed in 7.5% vs 8.6% in the DCB and BA
      groups, respectively. Angiographic follow-up performed after a mean follow-up of
      9.1 +/- 2.1 months demonstrated that DCB was associated with lower SB late lumen
      loss compared with BA (mean difference, -0.19 mm; 95% confidence interval [CI], 
      0.37 to -0.01; P=.04). There was no difference in the risk of SB binary
      restenosis (odds ratio [OR], 0.52; 95% CI, 0.18-1.47; P=.22). During a mean
      follow-up of 15.1 +/- 5.8 months, DCB and BA had similar risk of MACE (OR, 0.76;
      95% CI, 0.4-1.4; P=.40), and TLR (OR, 0.85; 95% CI, 0.3-2.4; P=.76). CONCLUSION:
      Assessment of DCB for SB treatment of coronary bifurcations is limited by low
      power due to the small number of patients studied. Use of DCB was associated with
      lower SB late lumen loss, but this did not translate into improved clinical
      outcomes.

PMID- 30218556
TI  - Validation of STS/ACC TVT-TAVR Score in Veterans Undergoing Transcatheter Aortic
      Valve Replacement.
AB  - BACKGROUND: The Society of Thoracic Surgeons (STS)/American College of Cardiology
      (ACC) transcatheter valve therapy (TVT) transcatheter aortic valve replacement
      (TAVR) score was developed to predict in-hospital mortality in patients
      undergoing commercial TAVR in the United States. Veterans Affairs (VA) hospitals
      are not included in the TVT registry. METHODS: The STS/ACC TVT-TAVR score was
      estimated in 195 veterans undergoing TAVR from 2015-2017. Discrimination was
      estimated by calculating the area under the receiver operating characteristics
      curve (AUC) for two outcomes of interest: in-hospital and 30-day mortality. The
      cohort was then divided into quartiles of TAVR and STS predicted risk of
      mortality (PROM) scores and long-term mortality was assessed with Kaplan-Meier
      curves. RESULTS: The mean age of the cohort was 77 +/- 8 years and the population
      was 99% males. The median TAVR and STS-PROM risk scores were 3.1 (interquartile
      range [IQR], 2.1-5.1) and 4.5 (IQR, 2.6-7.4), respectively. Observed in-hospital
      and 30-day mortality rates were 2.6% and 4.6%, respectively. The AUCs for the
      TAVR risk score were 0.68 and 0.64 for in-hospital and 30-day mortality,
      respectively. During a mean follow-up period of 1.9 years, a total of 37 patients
      (20%) died. Long-term survival was similar in different quartiles of STS-PROM
      scores (P=.52). In contrast, patients in the highest quartile of TAVR risk score
      (8.4; IQR, 5.8-9.9) had significantly worse survival (P<.01). This group included
      20 out of the 37 deaths (>50%). CONCLUSIONS: Developed and validated in
      commercial United States cases, the TAVR risk score has a similar performance in
      the veteran population for predicting short-term outcomes. In addition, the TAVR
      score predicts long-term mortality. Our results have implications for optimal
      patient selection.

PMID- 30218558
TI  - Editorial.
AB  - no summary.

PMID- 30218557
TI  - In-Hospital Outcomes of Chronic Total Occlusion Percutaneous Coronary
      Intervention in Patients With Chronic Kidney Disease.
AB  - OBJECTIVES: The effect of chronic kidney disease (CKD) on in-hospital outcomes of
      chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has
      received limited study. METHODS: We evaluated the prevalence of CKD and its
      impact on CTO-PCI outcomes in 1979 patients who underwent 2040 procedures between
      2012 and 2017 at 18 centers. CKD was defined as preprocedural estimated
      glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS: Compared with
      patients without CKD (n = 1444; 73%), patients with CKD (n = 535; 27%) had more
      comorbidities (hypertension, diabetes mellitus, heart failure, peripheral
      arterial disease, prior myocardial infarction, PCI, coronary artery bypass graft
      surgery, and stroke), and more severe calcification and proximal vessel
      tortuosity. Patients with and without CKD had similar technical success rates
      (84% vs 86%; P=.49) and procedural success rates (83% vs 84%; P=.44). Patients
      with CKD had higher in-hospital mortality rate (1.9% vs 0.3%; P<.001) and in
      hospital major adverse cardiovascular event (MACE) rate (4.3% vs 2.2%; P<.01). In
      hospital mortality and MACE rates increased with decreasing eGFR levels (P=.03).
      In multivariate analysis, an independent association was observed between CKD and
      in-hospital mortality (adjusted odd ratio, 4.4; 95% confidence interval, 1.2
      16.0; P=.02), but not overall MACE (adjusted odds ratio, 1.4; 95% confidence
      interval, 0.8-2.7; P=.28). CONCLUSIONS: CKD is common among patients undergoing
      CTO-PCI. High success rates can be achieved in patients with decreased glomerular
      filtration rate, but CKD may be associated with higher in-hospital mortality.

PMID- 30218559
TI  - Risk and prophylaxis of venous thromboembolism in hospitalized psychiatric
      patients. A review.
AB  - Venous thromboembolism (VTE) is a frequent dangerous complication occurring
      during hospital treatment with total annual incidence of 70-200 per 100,000
      citizens. Venous thromboembolism includes deep vein thrombosis (DVT) and
      pulmonary embolism (PE). Pulmonary embolism is responsible for about 10% of
      hospitalization-related deaths and is the most common avoidable reason for deaths
      in hospitals. Psychiatric inpatients are particularly vulnerable to an increased
      risk of VTE due to their limited mobility, the use of restraints, catatonia,
      communication difficulties, and the use of antipsychotics. Patients with chronic
      psychiatric conditions like schizophrenia and recurrent affective disorders have
      significantly higher somatic comorbidity. This population of patients requires
      specific approach to VTE prophylaxis during hospitalization. This article offers
      an insight into issues related to thromboembolism, and presents validated
      diagnostic tools and VTE prophylaxis strategies. The paper includes the review of
      available research on VTE in patients hospitalized for psychiatric reasons.
      Considering the scarcity of specific studies in this population we highlight the
      necessity to follow the available general medical guidelines for psychiatric
      inpatients.

PMID- 30218560
TI  - Inflammatory theory of depression.
AB  - Brain diseases are one of the most socially and economically burdening diseases
      in Europe. Among all brain diseases, more than 60% of social and economic costs
      are generated by mental disorders (mainly depressive disorders and anxiety
      disorders). Recurrent depressive disorders have been a significant civilizational
      problem in recent times. Among the biological and psychological theories
      explaining the causes of depression, the hypothesis involving an active
      inflammatory process taking place in a human organism is becoming increasingly
      important. The following are considered inflammation markers: inflammatory
      enzymes (e.g., manganese superoxide dismutase (MnSOD), myeloperoxidase (MPO),
      inducible nitric oxide synthase), proinflammatory and anti-inflammatory
      cytokines, and the phenomenon of oxidative stress. Through the kynurenine
      pathway, these factors lead to a deficit in serotonin and melatonin, which is
      considered one of the main reasons of depression. We can consider depression to
      be a chronic cold of the organism, which develops in response to the action of
      greater or smaller everyday stressors. This paper presents results of recent
      studies regarding this matter.

PMID- 30218561
TI  - Zinc and copper concentration do not differentiate bipolar disorder from major
      depressive disorder.
AB  - OBJECTIVES: The aim of this study was to compare the zinc and copper
      concentration in the group of patients with bipolar disorder (BD) and major
      depressive disorder (MDD). METHODS: 110 patients with the diagnosis of BD and 114
      with MDD were qualified to the study. To assess the levels of microelements, the
      flame atomic absorption spectrometry (FAAS) was used in the case of zinc and the
      electrothermal atomic absorption spectrometry (ETAAS) was used in the case of
      copper. RESULTS: There were no differences between concentration of zinc and
      copper in remission and depressive phase between patients with BD and MDD.
      Additionally, there were also no statistically significant differences in
      comparisons including type I and II, early or late phase of BD and MDD.
      CONCLUSIONS: The lack of differences in zinc and copper concentrations between
      patients with bipolar disorder and major depressive disorder might indicate that
      those disorders have similar etiology.

PMID- 30218562
TI  - Dopaminergic system activity under stress condition - seeking individual
      differences, preclinical studies.
AB  - Dopaminergic system activity in limbic structures (reward system) is related to
      motivational processes and adaptation to changing environmental conditions.
      Stress conditions can cause dopaminergic dysfunction, reduce motivational
      processes and induce compensatory drug use. The susceptibility to stress is
      characterized by individual variability. Psychostimulants such as cocaine,
      amphetamine and its derivatives act as positive reinforcers, affecting mood
      changes. Prolonged use of psychoactive substances can cause persistent plastic
      changes in the limbic system (disruption of neurogenesis, neurons atrophy),
      resulting in addictions or other forms of psychopathology like mood disorders.
      One of the reason is dysregulation of the dopaminergic system and dysfunction of
      local dopamine release in the nucleus accumbens. Stress factors also inhibit
      neuronal plasticity. In turn, antidepressants may increase brain-derived
      neurotrophic factor (BDNF) and TrkB receptors expression and improve neuronal
      proliferation, restoring proper functioning of the limbic regions. An important
      manifestation of the distinct functioning of the dopaminergic mesolimbic system
      is the difference between the sexes and the aging process. Epidemiological
      studies indicate that depression, anxiety disorders, and other emotional
      disorders often accompany drug abuse. The search for neurobiological basis of
      affective disorders and identification of factors, including epigenetic ones
      (interdependence of genetic and environmental factors), associated with different
      susceptibility to stress and predisposition to addiction to psychoactive
      substances is currently being carried out by many researches. Understanding the
      neurobiological factors of individual differences related to susceptibility to
      psychostimulants may aid in developing future therapies adapted to the patient's
      needs and more effective treatment of addiction.

PMID- 30218563
TI  - Resilience in persons with affective and anxiety disorders and the experience of
      early trauma - pilot studies.
AB  - OBJECTIVES: The primary goal of the study was to examine the role of ego
      resilience as a factor contributing to the relationship between early trauma and
      the incidence of psychopathology in adult life; and to make an attempt at
      identifying the relationship between resilience and personality traits and the
      early experience of trauma and the incidence of psychopathology in adult life in
      persons with affective and anxiety disorders. METHODS: The study involved 30
      patients of the Day Care Emotional and Mood Disorder Treatment Unit, University
      Hospital in Krakow, Poland, who were asked to complete the following inventories:
      the Early Trauma Inventory - Self Report, the NEO-PI-R, the Resilience Scale for
      Adults, and the Beck Depression Inventory. RESULTS: The vast majority of the
      participants (97%) experienced interpersonal trauma in childhood, mostly of
      physical (96.67%) and emotional (83.33%) type. The personality traits that would
      most frequently resurface in the participants were: Agreeableness (50%),
      Neuroticism (43.34%) and low Extraversion levels (36.67%). The highest score for
      resilience was obtained in Perception of Future (24.8 points) and the lowest in
      Personal Strength (9.73 points). The average level of the symptoms of depression
      in the sample was characteristic of mild depression (M = 22.83). CONCLUSIONS: The
      outcomes fail to confirm the relationship between depressive tendencies and
      childhood trauma, and depressive tendencies and personality traits. The analysis
      allows the conclusion that the incidence of mental disorders is not dependent on
      childhood trauma, but rather on resilience levels. Resilience may be a predictor
      of a positive personality profile and a protective factor against the incidence
      of the symptoms of depression.

PMID- 30218564
TI  - Exposure to traumatic experiences among people addicted to alcohol.
AB  - OBJECTIVES: The present studies point to high, i.e., approx. 70%, presence of at
      least one traumatic event over the life of people addicted to alcohol. METHODS:
      The study involved 240 people - 120 people were addicted to alcohol (clinical
      group), including 60 women and 60 men, and 120 people were not addicted to
      alcohol (control group), including 60 women and 60 men. All people from the study
      group were asked to complete: The TAA-SR traumatic events assessment
      questionnaire, the structured interview checking the presence of experienced
      trauma and the severity of post-traumatic symptoms (PTSD) according to DSM-IV,
      and the personal survey. RESULTS: People addicted to alcohol experienced more
      traumas than non-addicted ones. The number of traumas of addicted women was
      significantly lower compared to addicted men. People addicted to alcohol reported
      the first experience of trauma much faster than non-addicted ones. The vast
      majority of people from the clinical group (addicted individuals) declared that
      the addiction symptoms occurred after experiencing the first trauma. CONCLUSIONS:
      The present studies point to high, i.e., approx. 70%, presence of at least one
      traumatic event over the life of people addicted to alcohol.

PMID- 30218565
TI  - The Polish adaptation of the Life Events Checklist (LEC-5) for PTSD criteria from
      DSM-5.
AB  - OBJECTIVES: The aim of the study was the Polish adaptation of the Life Events
      Checklist (LEC-5), which is used to assess individual's traumatic events exposure
      for posttraumatic stress disorder (PTSD) criteria from DSM-5. METHODS: The study
      was conducted on 172 students of the University of Finance and Management in
      Warsaw, i.e., 68 women and 104 men, at the age between 17 and 49 (M = 22.74; SD =
      6.80). Reliability of LEC-5 was measured by the absolute stability method. Two
      repeated measurements with two week interval were conducted on the sample of 40
      students of the University of Finance and Management. Validity of LEC-5 was
      checked by the correlational analysis between the LEC-5 scales and the PTSD
      Diagnostic Scale for DSM-5 (PDS-5) and the Impact of Events Scale (IES) on the
      whole 172 sample of students. RESULTS: The magnitude of interclass correlation
      coefficients for all LEC-5 scales and high values of Cohen's kappa coefficients
      proved a high reliability of this tool. Significant correlations between all LEC
      5 scales and PDS-5 and IES scales were also obtained, which proved satisfactory
      validity of LEC-5. CONCLUSIONS: Obtained empirical results proved satisfying
      psychometric properties of LEC-5.

PMID- 30218566
TI  - Coping with stress, control of emotions and biochemical markers as a common
      protective element in the inflammatory response to stress.
AB  - OBJECTIVES: Based on a comprehensive approach to the problem of stress, we have
      decided to evaluate all components of a stress response - immunological (IL-1, IL
      2, IL-6, IL-10, CRP, TNF-alpha) and hormonal one (CRH, ACTH), as well as to
      evaluate the psychological indicators of stress, coping with stress, and
      controlling emotional reactions as psychological markers that predispose to the
      most beneficial adaption in relation to stressors affecting flight personnel
      taking part in peace missions abroad. METHODS: The research studies being the
      subject matter of the project were conducted among 113 antiterrorists and 123
      representatives of aircrew (236 respondents in total) who participated in peace
      missions outside Poland. The study was conducted both before departure and during
      the missions. The study included a biochemical evaluation (IL-1, IL-2, IL-6, IL
      10, CRP, TNF-alpha, CRH, ACTH) as well as a psychological assessment based on the
      Perceived Stress Scale by S. Cohen (PSS-10) and the Courtauld Emotional Control
      Scale (CECS) by M. Watson and S. Greer, and the COPE Inventory by J. Corver.
      RESULTS: Based on a statistical analysis of the variables, a relationship between
      the level of perceived stress and the methods of coping with it as well as
      between the selected methods of emotion control and inflammatory response
      indicators, was found. CONCLUSIONS: In difficult situations, accompanied by an
      increase in the variables responsible for the biochemical inflammatory response
      of an organism, the effective model of coping with difficult situations and
      emotioncontrol increases, while the subjective level of perceived stress drops.

PMID- 30218567
TI  - Coping with stress and the sense of quality of life in inmates of correctional
      facilities.
AB  - OBJECTIVES: The aim of the study was to examine the differences between groups of
      prison inmates distinguished according to the sense of quality of life in terms
      of their ways of coping with stress. METHODS: In order to verify the research
      hypotheses, the following instruments were used: (1) The sense of quality of life
      Questionnaire (SQLQ) by M. Stras-Romanowska (2007) and (2) the COPE Inventory by
      Carver, Scheier and Weintraub (1989). RESULTS: The results of the presented
      research have confirmed that the ways of coping with stress used by prison
      inmates are related to the sense of quality of life. This conclusion applies not
      only to overall sense of quality of life but also to all of its dimensions:
      psychophysical, psychosocial, personal, and metaphysical one. According to the
      assumed hypothesis, people with a high level of overall quality of life
      significantly more often than people with a low level of quality of life prefer
      active coping strategies, including strategies such as: Active coping, Planning,
      Searching for instrumental support, Searching for emotional support, Positive
      revaluation and development. Asimilar conclusion with minor modifications also
      applies to other dimensions of quality of life. CONCLUSIONS: Thus, the use of
      constructive ways of coping with stress - based on seeking support, personal
      activity in coping with problems and drawing conclusions from wrong life
      decisions - is related to higher level of quality of life.

PMID- 30218568
TI  - Stress coping styles in firemen exposed to severe stress.
AB  - OBJECTIVES: Emergency service workers such as firemen are exposed to severe
      stress, which may result in deteriorated functioning and development of
      posttraumatic stress disorder (PTSD). The aim of the presented study was to
      assess the stress coping styles of firemen exposed to severe stress, the
      prevalence of PTSD symptoms, and the correlation between them. METHODS: The study
      was carried out in a group of 147 Polish firemen. Two questionnaires were used:
      the Coping Inventory for Stressful Situations (CISS) and the PTSD Interview (PTSD
      I) in the Polish language version (K-PTSD). RESULTS: The study was carried out in
      a group of 147 Polish firemen. Two questionnaires were used: the Coping Inventory
      for Stressful Situations (CISS) and the PTSD Interview (PTSD-I) in the Polish
      language version (K-PTSD). CONCLUSIONS: Nearly one third of the investigated
      group of firemen suffered from symptoms of PTSD, with the stress coping strategy
      most often observed in that subgroup being style focused on avoidance. Age proved
      to be a factor associated with the readiness to undertake behavioral measures to
      cope with stress tension; such behavior tends to be undertaken by older firemen.

PMID- 30218569
TI  - Coping styles and dispositional optimism as predictors of post-traumatic stress
      disorder (PTSD) symptoms intensity in paramedics.
AB  - OBJECTIVES: The aim of the study was to determine the relationship between the
      severity of post-traumatic stress disorder (PTSD) symptoms and such predictors as
      coping style and dispositional optimism in the group of professional paramedics.
      METHODS: The study was conducted in a group of 440 paramedics employed by various
      units of the Polish Emergency Medical Service in five voivodships. Finally,
      research data obtained from 159 people were analyzed. The mean age of the
      respondents was 34.14 (SD = 8.67), mean work experience - 9.22 years (SD = 7.67).
      The majority of participants were male (N = 139, 87.4%), which reflects the
      gender balance observed in this particular professional group. Intensity of PTSD
      symptoms was assessed using the Impact of Event Scale - Revised (IES-R).
      Dispositional optimism was evaluated by means of the Life Orientation Test -
      Revised (LOT-R) and coping styles were measured with the use of the multi-faceted
      Coping Orientations to Problems Expected (COPE) inventory. RESULTS: On the basis
      of the conducted studies, it can be concluded that PTSD concerns 28% of the
      participants. Hierarchical regression analysis revealed that general risk of PTSD
      symptoms occurrence is caused by preferred coping style, namely the emotion
      focused coping style (positive predictor). Furthermore, two-factor interaction
      regression analysis showed that dispositional optimism can play a role as a
      mediator of the relationship between PTSD general index and the emotion-focused
      coping style. CONCLUSIONS: Paramedics are more prone to develop PTSD symptoms
      than general population. This indicates the need for preventive steps to be taken
      in the professional group of paramedics taking into consideration their coping
      styles and level of dispositional optimism.

PMID- 30218570
TI  - Does the family "need" depression? A pilot study of family consultations.
AB  - OBJECTIVES: The aim of the presented study was to analyse associations between
      drug-resistant depression and the way the illness is described by patients and
      members of their families. In particular, a hypothesis to be verified was that
      being ill may be a factor stabilising the family system, and consequently
      treatment of this kind of depression may encounter additional difficulties and
      enforce "drug-resistance" by "sustaining depression" by the family. METHODS: The
      study included 20 patients and their families. The consultations that were
      conducted with each of the families constituted data for the presented research.
      Initial results indicate an explicit association between the way the patient and
      his or her family define circumstances of the illness and treatment and the type
      of interactions between them that are manifested verbally and nonverbally.
      RESULTS: Results of qualitative analysis indicate that if a patient during
      consultation reflects on how to describe his or her situation and precipitating
      factors of the illness, it usually takes place in opposition to other members of
      the family of origin. On the other hand, if a patient manifests depressive
      symptoms, he or she assumes a dependent role, while the rest of the family
      express an attitude of warmth towards him or her. CONCLUSIONS: Drug resistance
      depression should be considered, also with the context of the patient's family.

PMID- 30218571
TI  - Social support as a determinant of life satisfaction in pregnant women and women
      after surgical delivery.
AB  - OBJECTIVES: The aim of the study was to determine whether social support obtained
      by women in the third trimester of pregnancy and in the postpartum period differs
      significantly with respect to the mode of delivery and whether there is a
      difference in the life satisfaction of the studied women.. METHODS: The study
      included 195 women in the third trimester of pregnancy and 182 women from the
      same group after delivery. The Berlin Social Support Scales (BSSS) and the
      Satisfaction with Life Scale (SWLS) were used in the study. RESULTS: As early as
      in the third trimester of pregnancy, women who later underwent Caesarean section
      received significantly more support of all types than women who gave birth
      physiologically. In the postpartum period, post-Caesarean women received
      significantly more support of only instrumental nature. No statistically
      significant differences were found with respect to life satisfaction of the
      studied groups of women. CONCLUSIONS: The results of the present study
      demonstrate that Caesarean section does not provide greater life satisfaction.
      Instrumental support plays a crucial role in meeting the caring needs of post
      Caesarean women in the postpartum period. The study reveals which type of support
      is needed by women and highlights the significant role of fathers during
      childbirth.

PMID- 30218572
TI  - Plasma progesterone, estradiol, and unconjugated estriol concentrations in twin
      pregnancies: Relation with cervical length and preterm delivery.
AB  - INTRODUCTION: The aim was to examine the association between plasma hormone
      concentrations, cervical length, and preterm delivery in twin pregnancies,
      including the effect of progesterone treatment. MATERIAL AND METHODS: This study
      included 191 women pregnant with twins from a randomized placebo-controlled
      trial. A baseline blood sample was collected at 18-24 weeks before treatment with
      vaginal progesterone (n = 95) or placebo pessaries (n = 96), and 167 (87.4%)
      women had a second sample collected after 4-8 weeks of treatment. At baseline,
      155 (81.2%) women had their cervical length measured. Progesterone, estradiol,
      and unconjugated estriol concentration was measured, and the association between
      hormone concentrations, cervical length, and gestational age at delivery was
      examined. Hormone concentrations were compared in the placebo and progesterone
      group. Statistical analysis included Spearman's rho, Mann-Whitney U test,
      Cuzick's test for trends, and linear regression analyses. RESULTS: A short
      cervical length was associated with preterm delivery. Cervical length and hormone
      concentrations were not associated (Spearman's rho; progesterone -.05, estradiol
      .04, estriol .08). Decreasing gestational age at delivery was associated with
      higher progesterone and estradiol concentrations at baseline (P trend;
      progesterone 0.04, estradiol 0.02) but not in the second sample or in the weekly
      change between samples. Progesterone treatment did not increase the progesterone
      concentration. CONCLUSION: Plasma concentrations of progesterone, estradiol, and
      unconjugated estriol at 18-24 weeks are not associated with cervical length or
      preterm delivery in twin pregnancies. Vaginal progesterone treatment does not
      increase the circulating progesterone concentration in twin pregnancies. Cervical
      length, but not hormone concentration, is predictive of preterm delivery in twin
      gestations.

PMID- 30218573
TI  - TMP778, a selective inhibitor of RORgammat, suppresses experimental autoimmune
      uveitis development, but affects both Th17 and Th1 cell populations.
AB  - Experimental autoimmune uveitis (EAU), an animal model for severe intraocular
      inflammatory eye diseases, is mediated by both Th1 and Th17 cells. Here, we
      examined the capacity of TMP778, a selective inhibitor of RORgammat, to inhibit
      the development of EAU, as well as the related immune responses. EAU was induced
      in B10.A mice by immunization with interphotoreceptor retinoid-binding protein
      (IRBP). Treatment with TMP778 significantly inhibited the development of EAU,
      determined by histological examination. In addition, the treatment suppressed the
      cellular immune response to IRBP, determined by reduced production of IL-17 and
      IFN-gamma, as well as lower percentages of lymphocytes expressing these
      cytokines, as compared to vehicle-treated controls. The inhibition of IFN-gamma
      expression by TMP778 is unexpected in view of this compound being a selective
      inhibitor of RORgammat. The observation was further confirmed by the finding of
      reduced expression of the T-bet (Tbx21) gene, the transcription factor for IFN
      gamma, by cells of TMP778-treated mice. Thus, these data demonstrate the capacity
      of TMP778 to inhibit pathogenic autoimmunity in the eye and shed new light on its
      mode of action in vivo.

PMID- 30218574
TI  - Why don't mice lacking the mitochondrial Ca2+ uniporter experience an energy
      crisis?
AB  - Current dogma holds that the heart balances energy demand and supply effectively
      and sustainably by sequestering enough Ca2+ into mitochondria during heartbeats
      to stimulate metabolic enzymes in the tricarboxylic acid (TCA) cycle and electron
      transport chain (ETC). This process is called excitation-contraction
      bioenergetics (ECB) coupling. Recent breakthroughs in identifying the
      mitochondrial Ca2+ uniporter (MCU) and its associated proteins have opened up new
      windows for interrogating the molecular mechanisms of mitochondrial Ca2+
      homeostasis regulation and its role in ECB coupling. Despite remarkable progress
      made in the past 7 years, it has been surprising, almost disappointing, that
      germline MCU deficiency in mice with certain genetic background yields viable
      pups, and knockout of the MCU in adult heart does not cause lethality. Moreover,
      MCU deficiency results in few adverse phenotypes, normal performance, and
      preserved bioenergetics in the heart at baseline. In this review, we briefly
      assess the existing literature on mitochondrial Ca2+ homeostasis regulation and
      then we consider possible explanations for why MCU-deficient mice are spared from
      energy crises under physiological conditions. We propose that MCU and/or
      mitochondrial Ca2+ may have limited ability to set ECB coupling, that other
      mitochondrial Ca2+ handling mechanisms may play a role, and that extra
      mitochondrial Ca2+ may regulate ECB coupling. Since the heart needs to regenerate
      a significant amount of ATP to assure the perpetuation of heartbeats, multiple
      mechanisms are likely to work in concert to match energy supply with demand.

PMID- 30218575
TI  - Precision and reproducibility of automated computer-guided Psoriasis Area and
      Severity Index measurements in comparison with trained physicians.
AB  - BACKGROUND: The Psoriasis Area and Severity Index (PASI) represents the gold
      standard for psoriasis severity assessments but is limited by its subjectivity
      and low intra- and inter-rater consistency. OBJECTIVES: To investigate the
      precision and reproducibility of automated, computer-guided PASI measurements
      (ACPMs) in comparison with three trained physicians. METHODS: This was a
      comparative observational study assessing ACPMs attained by automated total-body
      imaging and computerized digital image analysis in a cohort of 120 patients
      affected by plaque psoriasis of various severities. The level of agreement
      between ACPMs and physicians' PASI measurements was calculated by the intraclass
      correlation coefficient (ICC). The reproducibility of ACPMs in comparison with
      physicians' PASI measurements was investigated by performing two successive
      'repeat PASI calculations' in the same patients. RESULTS: The agreement between
      ACPMs and physicians' PASI calculations in 120 fully evaluable patients was high
      (ICC 0.86, 95% confidence interval 0.80-0.90, mean absolute difference 2.5 PASI
      points). Repeat ACPMs to measure the reproducibility showed an excellent ICC of
      0.99 (95% confidence interval 0.98-0.99) with a mean absolute difference of 0.5
      PASI points. The ACPMs thus outperformed the three physicians for intrarater
      reliability (mean ICC 0.86). CONCLUSIONS: The results of this first clinical
      study investigating ACPMs in 120 patients with psoriasis indicate a similar
      precision and higher reproducibility in comparison with trained physicians.
      Limitations arise from poorly observable body sites and from patients unable to
      attain predefined postures during automated image acquisition.

PMID- 30218576
TI  - Frequency Offset Corrected Inversion Pulse for B0 and B1 Insensitive Fat
      Suppression at 3T: Application to MR Neurography of Brachial Plexus.
AB  - BACKGROUND: The 3D short tau inversion recovery (STIR) sequence is routinely used
      in clinical MRI to achieve robust fat suppression. However, the performance of
      the commonly used adiabatic inversion pulse, hyperbolic secant (HS), is
      compromised in challenging areas with increased B0 and B1 inhomogeneities, such
      as brachial plexus at 3T. PURPOSE: To demonstrate the frequency offset corrected
      inversion (FOCI) pulse as an efficient fat suppression STIR pulse with increased
      robustness to B0 and B1 inhomogeneities at 3T, compared to the HS pulse. STUDY
      TYPE: Prospective. SUBJECTS/PHANTOM: Initial evaluation was performed in phantoms
      and one healthy volunteer by varying the B1 field, while subsequent comparison
      was performed in three healthy volunteers and five patients without varying the
      B1 . FIELD STRENGTH/SEQUENCE: 3T; 3D TSE-STIR with HS and FOCI pulses.
      ASSESSMENT: Brachial plexus images were qualitatively evaluated by two
      musculoskeletal radiologists independently using a four-point grading scale for
      fat suppression, shading artifacts, and nerve visualization. STATISTICAL TEST:
      The Wilcoxon signed-rank test with P < 0.05 was considered statistically
      significant. RESULTS: Simulations and phantom experiments demonstrated broader
      bandwidth (2.5 kHz vs. 0.83 kHz, increased B0 robustness) at the same adiabatic
      threshold and lower adiabatic threshold (5 MUT vs. 7 MUT at 3.5 ppm, increased B1
      robustness) at the same bandwidth with the FOCI pulse compared to the HS pulse
      With increased bandwidth, the FOCI pulse achieved robust fat suppression even at
      50% of maximum B1 strength, while the HS pulse required >75% of maximum B1
      strength. Compared to the standard 3D TSE-STIR with HS pulse, the FOCI pulse
      achieved uniform fat suppression (P < 0.05), better nerve visualization (P <
      0.05), and minimal shading artifacts (P < 0.01) in brachial plexus at 3T. DATA
      CONCLUSION: The FOCI pulse has increased robustness to B0 and B1 inhomogeneities,
      compared to the HS pulse, and enables uniform fat suppression in brachial plexus
      at 3T. LEVEL OF EVIDENCE: 1 Techinical Efficacy: Stage 1 J. Magn. Reson. Imaging
      2018;48:1104-1111.

PMID- 30218578
TI  - Effects of hydroxyurea on CNV induction in the mouse germline.
AB  - Copy number variants (CNVs) are important in genome variation and genetic
      disease, with new mutations arising frequently in the germline and somatic cells.
      Replication stress caused by aphidicolin and hydroxyurea (HU) is a potent inducer
      of de novo CNVs in cultured mammalian cells. HU is used extensively for long-term
      management of sickle cell disease. Here, we examined the effects of HU treatment
      on germline CNVs in vivo in male mice to explore whether replication stress can
      act as a CNV mutagen in germline mitotic divisions as in cultured cells and
      whether this would support a concern for increased CNV mutations in offspring of
      men treated with HU. Several trials of HU administration were performed by oral
      gavage and subcutaneous pump, with CNVs characterized in C57BL/6 x C3H/HeJ hybrid
      mouse offspring by microarray and mate-pair sequencing. HU had a short half-life
      of ~14 min and a narrow dose window over which studies could be performed while
      maintaining fertility. Tissue histopathology and reticulocyte micronucleus assays
      verified that doses had a substantial tissue and genetic toxicity. CNVs were
      readily detected in offspring that originated in both paternal and maternal mouse
      strains, as de novo and inherited events. However, HU did not increase CNV
      formation above baseline levels. These results reveal a high rate of CNV
      mutagenesis in the mouse germline but do not support the hypothesis that HU would
      increase CNV formation during mammalian spermatogenesis, perhaps due to highly
      toxic effects on sperm development or experimental variables related to HU
      pharmacology in mice. Environ. Mol. Mutagen. 59:698-714, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30218577
TI  - Liver transplantation for fulminant hepatitis due to yellow fever.
AB  - A previously healthy 27-year-old female had 3 days of fever (40 degrees C),
      headache, and myalgia. She had not been previously vaccinated for YF. Initial
      workup revealed 2,150 leukocytes/mm3 , 83,000 platelets/mm3 , AST 8462U/L and ALT
      5249U/L (Figure 1). She was icteric with a heart rate of 60 bpm. The following
      day, a generalized seizure led to intubation, and renal failure led to
      hemodialysis. Transcranial doppler ultrasound showed signs of intracranial
      hypertension, cranial CT scan showed diffuse hypoattenuation and loss of grey
      white differentiation; abdominal doppler ultrasound, and echocardiogram were
      normal. This article is protected by copyright. All rights reserved.

PMID- 30218579
TI  - Inflammatory disorders associated with trisomy 8-myelodysplastic syndromes:
      French retrospective case-control study.
AB  - OBJECTIVE: We report cases of myelodysplastic syndrome/myeloproliferative
      neoplasms (MDS/MPN) with trisomy 8 associated with inflammatory and autoimmune
      diseases (IADs). METHOD: Data for 21 patients with trisomy 8-MDS/MPN and IADs
      were analyzed and compared to 103 patients with trisomy 8-MDS/MPN without IADs.
      RESULTS: The median age of MDS/MPN patients with IADs was 67 [59-80]. The IADs
      were Behcet's-like disease in 11 (52%) patients, inflammatory arthritis in 4
      (19%) and Sjogren's syndrome, autoimmune hemolytic anemia, aseptic abscess,
      periarteritis nodosa, Sweet's syndrome and unclassified vasculitis in one patient
      each. Overall, 17/21 (81%) patients with IADs received treatment (88% with
      steroids), with complete and partial response in 7/17 (35%) and 8/17 (47%),
      respectively. The effect of MDS treatment on IADs could be assessed in seven
      patients receiving azacytidine: five achieved remission and two partial response.
      As compared with the 103 trisomy 8-MDS/MPN cases without IADs, those with IADs
      were more often non-European (P = 0.005) and had poor karyotype (P < 0.001). We
      found no difference in overall survival or acute myeloid leukemia progression
      between trisomy 8-associated MDS/MPN with and without IADs. CONCLUSION: The
      spectrum of IADs associated with trisomy 8-positive MDS/MPN is dominated by
      Behcet's-like disease. Steroid therapy is effective, but mostly sparing therapies
      are necessary. Azacytidine could be an effective alternative.

PMID- 30218580
TI  - A new approach to kidney wait-list management in the kidney allocation system
      era: Pilot implementation and evaluation.
AB  - Kidney transplant wait-list management is becoming increasingly complex. We
      introduced a novel wait-list management strategy at our center, the Transplant
      Readiness Assessment Clinic (TRAC), whereby patients whose Kidney Allocation
      Scores surpass a threshold are actively managed. From January 1, 2016 through
      June 30, 2017, we evaluated 195 patients through TRAC. Compared to pre-TRAC
      systems at our institution, TRAC resulted in a higher proportion of activation at
      18 months (38% vs 22%-26%, P < 0.0001), despite being enriched in patients with
      long dialysis duration. TRAC also resulted in a higher proportion of wait-list
      removal (15% vs 8%-9%, P < 0.05) although combined wait-list removal and death on
      wait-list did not differ (18% vs 16%-17%). Median time to activation was 356 days
      from TRAC evaluation. Of the transplant barriers, need for cardiovascular studies
      was the most common (31%), followed by other medical issues (23%), poor
      functional status (13%), and psychosocial issues (10%). By concentrating center
      resources on patients most likely to be transplanted after activation and
      performing active patient management close to the time of transplant, TRAC has
      the potential to significantly enhance kidney transplant success in regions with
      long wait-times.

PMID- 30218581
TI  - A hyperactive mutant of interferon-regulatory factor 4.
AB  - We found that deletion of the final 30 amino acids of transcription factor IRF4's
      (interferon-regulatory factor) C-terminus creates hyperactive IRF4. When
      introduced into IRF4-deficient CD4+ or CD8+ T cells, more type 17 differentiation
      was found compared to WT IRF4. Interestingly, Th9 differentiation and Th2-linked
      IL-13 production were much less altered.

PMID- 30218582
TI  - Histone H3K9 demethylase JMJ25 epigenetically modulates anthocyanin biosynthesis
      in poplar.
AB  - Anthocyanins are involved in several aspects of development and defence in poplar
      (Populus spp.). Although, over the past decades, significant progress has been
      made in uncovering these anthocyanin biosynthetic and regulatory mechanisms, the
      fundamental understanding of the epigenetic regulation in this pathway is still
      largely unclear. Here, we isolated a histone H3K9 demethylase gene JMJ25 from
      Populus and characterized its role in anthocyanin biosynthesis by genetic and
      biochemical approaches. JMJ25 was induced by continuous dark treatment.
      Overexpression of JMJ25 led to downregulated expression of anthocyanin
      biosynthetic genes in transgenic poplar, resulting in a significant reduction in
      anthocyanin content. ChIP-qPCR assays showed that JMJ25 could directly associate
      with MYB182 chromatin and dynamically demethylate at H3K9me2. Furthermore, JMJ25
      also affected the DNA methylation levels of MYB182. By contrast, knockout of
      JMJ25 by CRISPR/Cas9 resulted in ectopic anthocyanin accumulation under dark
      condition and increased expression of anthocyanin biosynthetic genes. Our results
      support a model in which JMJ25 directly affects MYB182 expression by altering the
      histone methylation status of its chromatin and DNA methylation, resulting in
      repression of anthocyanin accumulation. This study uncovered an epigenetic
      mechanism that modulates anthocyanin biosynthesis in poplar.

PMID- 30218583
TI  - Validation of Risk Score in Predicting Early Readmissions in Decompensated
      Cirrhotic patients: A Model Based on the Administrative Database.
AB  - INTRODUCTION: The early readmission in patients with decompensated liver
      cirrhosis leads to enormous burden on healthcare utilization. METHODS:
      Retrospective cohort study using the 2013 and 2014 Nationwide Readmission
      Database (NRD) was conducted. Patients with diagnoses of cirrhosis and at least
      one feature of decompensation were included. The primary outcome was to develop a
      validated risk model for early readmission. Secondary outcomes were to study 30
      day all cause-readmission rate and most common reasons for readmission.
      Multivariable logistic regression model was fit to identify predictors of
      readmissions. Finally, a risk model named as Mumtaz Readmission risk score was
      developed for prediction of 30-day readmission based on 2013 NRD and validated on
      2014 NRD. RESULTS: A total of 123,011 patients were included. The 30-day
      readmission rate was 27%. 79.6% of patients were readmitted with liver related
      diagnoses. Age <65 years, Medicare or Medicaid insurance, non-alcoholic etiology
      of cirrhosis, >=3 Elixhauser score, presence of hepatic encephalopathy (HE),
      ascites, variceal bleeding, hepatocellular carcinoma, paracentesis, hemodialysis
      and discharge against medical advice were independent predictors of 30-day
      readmission. This validated model enabled patients with decompensated cirrhosis
      to be stratified into low (<20%), medium, (20-30%) and high (>30%) risk of 30-day
      readmissions. CONCLUSION: One third of patients with decompensated cirrhosis are
      readmitted within 30 days of discharge. The use of simple risk scoring model with
      high generalizability, based on demographics, clinical features and interventions
      can bring refinement to the prediction of 30-day readmission in high risk
      patients. Mumtaz readmission risk score highlights the need for targeted
      interventions in order to decrease rates of readmission within this population.
      This article is protected by copyright. All rights reserved.

PMID- 30218584
TI  - The neuronal migration hypothesis of dyslexia: A critical evaluation 30 years on.
AB  - The capacity for language is one of the key features underlying the complexity of
      human cognition and its evolution. However, little is known about the
      neurobiological mechanisms that mediate normal or impaired linguistic ability.
      For developmental dyslexia, early postmortem studies conducted in the 1980s
      linked the disorder to subtle defects in the migration of neurons in the
      developing neocortex. These early studies were reinforced by human genetic
      analyses that identified dyslexia susceptibility genes and subsequent evidence of
      their involvement in neuronal migration. In this review, we examine recent
      experimental evidence that does not support the link between dyslexia and
      neuronal migration. We critically evaluate gene function studies conducted in
      rodent models and draw attention to the lack of robust evidence from
      histopathological and imaging studies in humans. Our review suggests that the
      neuronal migration hypothesis of dyslexia should be reconsidered, and the
      neurobiological basis of dyslexia should be approached with a fresh start.

PMID- 30218586
TI  - Effect of sitagliptin, a DPP-4 inhibitor, against DENA-induced liver cancer in
      rats mediated via NF-kappaB activation and inflammatory cytokines.
AB  - The target of the current research was to investigate the anticancer activity of
      sitagliptin on diethylnitrosamine (DENA)-induced cancer in the liver. Wistar rats
      were treated with or without sitagliptin before DENA treatment. We detected liver
      weight, blood glucose, and histopathology of the liver. Serum biochemical markers
      like serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate
      transaminase (SGOT), serum alkaline phosphatase (SALP), gamma-glutamyl
      transpeptidase (GGTP), total bilirubin (TBR), total protein (TPR), and albumin
      (ALB) were also evaluated. In addition, lipid profile parameters comprising total
      cholesterol (TC), triglycerides, and high-density lipoprotein were also measured.
      Inflammatory mediators like interleukin-6 (IL-6), interleukin-1beta (IL-1beta),
      and tumor necrosis factor-alpha (TNF-alpha) were determined in liver homogenate.
      Furthermore, the activity of nuclear factor (NF-kappaB) was also measured. Our
      results showed that sitagliptin (10 and 20 mg/kg) in a dose-dependent manner
      expressively decreased the DENA-induced elevation of SGPT, SGOT, SALP, and GGTP.
      Whereas sitagliptin (10 and 20 mg/kg) in a dose-dependent mode reduced the level
      of TBR and increased the TPR and ALB as well as improved the liver histopathology
      alterations in DENA-exposed rats. Lipid profile was also restored by the
      sitagliptin (10 and 20 mg/kg) in a DENA-treated rats. The level of IL-1beta, IL
      6, and TNF-alpha were suggestively suppressed. Moreover, pretreatment with
      sitagliptin (10 and 20 mg/kg) prevented the activation of NF-kappaB. In
      conclusion, sitagliptin (10 and 20 mg/kg) has a potential protective effect
      against DENA-induced liver cancer by inhibition of inflammation and NF-kappaB
      activation.

PMID- 30218587
TI  - Osteoanabolic and Dual Action Drugs.
AB  - Teriparatide (TPTD) and Abaloparatide (ABL) are the only osteoanabolic drugs
      available, at this time, for treatment of osteoporosis. TPTD is a 34-amino acid
      fragment that is identical in its primary sequence to the 34 amino acids of full
      length human parathyroid hormone [hPTH(1-84)]. ABL is identical to parathyroid
      hormone related peptide (PTHrP) through the first 22 residues with significantly
      different amino acids inserted thereafter, between residues 22 and 34. The
      osteoanabolic actions of PTH are due directly to its effects on cells of the
      osteoblast lineage and indirectly by stimulating IGF-I synthesis and suppressing
      sclerostin and associated enhancement of Wnt signaling. Both TPTD and ABL are
      ligands that bind to and activate the PTH receptor type 1 (PTHR1) receptor but
      they appear to do so differently: ABL favors the transient, more anabolic
      configuration of the receptor. Both TPTD and ABL reduce the risk of vertebral
      fractures and non-vertebral fractures. Both drugs are administered for a maximum
      of 24 months, and should be followed by an anti-resorptive agent to maintain
      gains in BMD. Romosozumab, a monoclonal antibody that binds to and inhibits
      sclerostin, appears to have dual actions by stimulating bone formation and
      reducing bone resorption. In the pivotal clinical trial, romosozumab,
      administered as a 210 mg monthly subcutaneous dose, significantly reduced new
      vertebral fractures and in a subsequent study reduced both vertebral and non
      vertebral fractures.

PMID- 30218585
TI  - Nicotine modulates human brain plasticity via calcium-dependent mechanisms.
AB  - KEY POINTS: Nicotine (NIC) modulates cognition and memory function by targeting
      the nicotinic ACh receptor and releasing different transmitter systems
      postsynaptically. With both NIC-generated mechanisms, calcium influx and calcium
      permeability can be regulated, which is a key requirement for the induction of
      long-term potentiation, comprising the physiological basis of learning and memory
      function. We attempt to unmask the underlying mechanism of nicotinic effects on
      anodal transcranial direct current stimulation (tDCS)-induced long-term
      potentiation-like plasticity based on the hypothesis of calcium-dependency.
      Abolished tDCS-induced neuroplasticity as a result of NIC administration is
      reversed by calcium channel blockade with flunarizine in a dose-dependent manner.
      The results of the present study suggest that there is a dose determination of
      NIC/NIC agonists in therapeutical settings when treating cognitive dysfunction,
      which partially explains the heterogeneous results on cognition observed in
      subjects in different experimental settings. ABSTRACT: Nicotine (NIC) modulates
      neuroplasticity and improves cognitive performance in animals and humans mainly
      by increased calcium permeability and modulation of diverse transmitter systems.
      NIC administration impairs calcium-dependent plasticity induced by non-invasive
      brain stimulation with transcranial direct current stimulation (tDCS) in non
      smoking participants probably as a result of intracellular calcium overflow. To
      test this hypothesis, we analysed the effect of calcium channel blockade with
      flunarizine (FLU) on anodal tDCS-induced cortical excitability changes in healthy
      non-smokers under NIC. We applied anodal tDCS combined with NIC patch and FLU at
      three different doses (2.5, 5 and 10 mg) or with placebo medication. NIC
      abolished anodal tDCS-induced neuroplasticity. Under medium dosage (but not under
      low and high dosage) of FLU combined with NIC, plasticity was re-established. For
      FLU alone, the lowest dosage weakened long-term potentiation (LTP)-like
      plasticity, whereas the highest dosage again abolished tDCS-induced plasticity.
      The medium dosage turned LTP-like plasticity in long-term depression-like
      plasticity. The results of the present study suggest a key role of calcium influx
      and calcium levels in nicotinic effects on LTP-like plasticity in humans. This
      knowledge might be relevant for the development of new therapeutic strategies in
      cognitive dysfunction.

PMID- 30218588
TI  - Oxygen responses within the nucleus accumbens are associated with individual
      differences in effort exertion in rats.
AB  - Goal-directed motivated behaviour is crucial for everyday life. Such behaviour is
      often measured, in rodents, under a progressive ratio (PR) schedule of
      reinforcement. Previous studies have identified a few brain structures critical
      for supporting PR performance. However, the association between neural activity
      within these regions and individual differences in effort-related behaviour is
      not known. Presently, we used constant potential in vivo oxygen amperometry, a
      surrogate for functional resonance imaging in rodents, to assess changes in
      tissue oxygen levels within the nucleus accumbens (NAc) and orbitofrontal cortex
      (OFC) in male Wistar rats performing a PR task. Within both regions, oxygen
      responses to rewards increased as the effort exerted to obtain the rewards was
      larger. Furthermore, higher individual breakpoints were associated with greater
      magnitude NAc oxygen responses. This association could not be explained by
      temporal confounds and remained significant when controlling for the different
      number of completed trials. Animals with higher breakpoints also showed greater
      magnitude NAc oxygen responses to rewards delivered independently of any
      behaviour. In contrast, OFC oxygen responses were not associated with individual
      differences in behavioural performance. The present results suggest that greater
      NAc oxygen responses following rewards, through a process of incentive
      motivation, may allow organisms to remain on task for longer and to overcome
      greater effort costs.

PMID- 30218589
TI  - Differential diagnosis of mesenchymal neoplasms of the digestive tract by cell
      block and immunohistochemistry.
AB  - OBJECTIVES: To evaluate the diagnostic yield of the cell block (CB) technique
      with immunohistochemistry in patients with mesenchymal neoplasms of the
      gastrointestinal tract collected by endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA). METHODS: Tissue samples from consecutive patients with
      subepithelial lesions collected by EUS-FNA, without analysis by on-site
      cytopathology, were evaluated by the same pathologist only using CBs in AAF
      fixative. Sections were stained with haematoxylin-eosin and underwent
      complementary immunohistochemical staining for SMA, CD117, DOG-1 and S100 in the
      presence of mesenchymal neoplasms. Specimens were defined as diagnostic when
      sufficient tissue was present for histopathological evaluation and
      immunohistochemistry analysis. If they were insufficient for complete evaluation,
      the specimens were considered nondiagnostic. RESULTS: Between September 2012 and
      December 2016, a total of 158 patients (median age: 57 years, 64.5% women)
      underwent EUS-FNA with an average of three needle passes for every lesion. The
      median lesion size was 17 mm. There were 113 mesenchymal neoplasms confirmed by
      immunohistochemistry (66 leiomyomas, 44 GISTs, two schwannomas, one
      leiomyosarcoma). The overall diagnostic yield of CBs was 84.17%. However,
      diagnosis was obtained in 98.5% (133/135) of the cases after exclusion of 23
      cases in which EUS-FNA sampling was insufficient or without tumoural tissue. Only
      two mesenchymal neoplasms were not confirmed by CBs even after
      immunohistochemistry. CONCLUSIONS: CBs collected by EUS-FNA and analysed by
      immunohistochemistry showed a high diagnostic yield in patients with mesenchymal
      neoplasms, even without on-site cytopathology.

PMID- 30218590
TI  - Sexual conflict and the maintenance of genetic variation in natural populations.
AB  - Understanding the factors that maintain genetic variation in natural populations
      is a foundational goal of evolutionary biology. To this end, population
      geneticists have developed a variety of models that can produce stable
      polymorphisms. In one of the earliest models, Owen () demonstrated that
      differences in selection pressures acting on males and females could maintain
      multiple alleles of a gene at a stable equilibrium. If the selection pressures
      act in opposite directions in males and females, we refer to this as (inter-)
      sexual conflict or sexual antagonism (Arnqvist & Rowe, ). Testing if sexual
      conflict maintains genetic variation in natural populations is a tremendous
      challenge-it requires both identifying loci that harbor sexually antagonistic
      alleles and determining whether those alleles are maintained as stable
      polymorphisms (Mank, ). Doing so genome-wide is even harder because it is not
      tractable to identify sexually antagonistic alleles and test for stable
      polymorphisms at all loci. Dutoit et al. () confront this challenge in a paper
      published in this issue of Molecular Ecology. Using gene expression and
      population genomic data from the collared flycatcher, Dutoit et al. () identify
      associations and correlations between genomic signatures of balanced
      polymorphisms and sexual conflict.

PMID- 30218591
TI  - Hepatology Highlights.

PMID- 30218592
TI  - Aeromonas spp. from marketed Yesso scallop (Patinopecten yessoensis): molecular
      characterization, phylogenetic analysis, virulence properties and antimicrobial
      susceptibility.
AB  - AIMS: Yesso scallop (Patinopecten yessoensis) is a popular seafood in Korea.
      Aeromonas spp., well-known pathogenic bacteria, has been reported in some
      molluscan shellfish, but it has not been studied in scallops so far. Therefore,
      we aimed to isolate, identify and characterize the Aeromonas spp. isolated from
      marketed Yesso scallops to estimate their potential risk to public health.
      METHODS AND RESULTS: Thirty-two Aeromonas spp. including A. hydrophila (n = 13),
      A. salmonicida (n = 11), A. media (n = 3), A. caviae (n = 2), A. veronii (n = 2)
      and A. enteropelogenes (n = 1) were isolated from 105 marketed scallops and
      tested for phenotypic pathogenicity, virulence genes and antimicrobial
      susceptibility. Mean total bacterial count of scallop meat was 1.34 * 104 CFU per
      gram. Slime production and lipase tests were positive in 97% of the isolates
      while DNase, protease, gelatinase, phospholipase and haemolysis were shown by 88,
      88, 81, 88 and 72% of the isolates respectively. Eleven virulence genes were
      detected among Aeromonas spp. (act (75%), alt (59%), ast (47%), aerA (78%), lip
      (59%), ahyB (94%), ser (75%), hlyA (75%), fla (64%), gcat (84%) and ascV (23%)),
      and exu was negative in all isolates. Aeromonas hydrophila and A. salmonicida
      harboured >=7 virulence genes and positive for enterotoxin genes, act, alt and
      ast. All the isolates were multidrug resistant and 100% resistant to ampicillin,
      colistin, vancomycin and cephalothin. Also, 30, 31, 20, 21, 29, 24, 27 and 27 of
      the isolates were resistant to piperacillin, clindamycin, erythromycin, nalidixic
      acid, imipenem, meropenem, trimethoprim-sulfamethoxazole and rifampicin
      respectively. CONCLUSIONS: It is obvious with our results that the Aeromonas spp.
      isolated from Yesso scallops are highly virulent and potentially pathogenic,
      whereas the multidrug resistance further expedite their importance. SIGNIFICANCE
      AND IMPACT OF THE STUDY: To our knowledge, this is the first study reporting
      Aeromonas spp. in scallop. This implies that not only the common varieties like
      oysters, but other bivalves can also harbour potentially pathogenic aeromonads
      which may have impacts on consumer health.

PMID- 30218593
TI  - Detection of Angiotensin II type I-receptor antibodies in transplant
      glomerulopathy.
AB  - BACKGROUND: Transplant glomerulopathy (TG) is an important cause of late graft
      loss. The role of angiotensin type 1-receptor antibodies (AT1 R-Ab) in TG is not
      known. METHODS: All the TG cases (N = 137) between January 2007 and December 2014
      (N = 1410) were analyzed. Donor-specific anti-HLA antibodies (DSA) at the time of
      biopsy and AT1 R-Ab IgG (positive, >17 UI/mL; "at risk," 10-17 UI/mL; negative,
      <10 UI/mL) in pre-transplant sera (PT-Ab) and at biopsy time (BT-Ab) were
      studied. RESULTS: AT1 R-PT-Ab+ and AT1 R-BT-Ab+ patients were 16.5% (51.5% "at
      risk") and 11.5% (27.4% "at risk"), respectively. Clinical correlations were
      found between AT1 R-Ab and HCV infection, number of transplants, and age.
      Considering Banff scores, ptc was higher in DSA+ patients vs AT1 R-PT-Ab+ (P =
      0.002) or AT1 R-BT-Ab+ (P = 0.001) without differences in g and chronicity score
      (ci + ct); cg showed lower scores in DSA+ patients vs AT1 R-BT-Ab+ (P = 0.001).
      Graft survival was not influenced by the presence of AT1 R-Ab, AT1-R-Ab titer or
      MFI, but we observed a longer graft survival in patients with both AT1 R-BT-Ab+
      or "at risk" and DSA+ vs patients positive only for DSA (P = 0.02), for AT1 R-BT
      Ab (P = 0.019) or AT1 R-BT-Ab "at risk" (P = 0.039). CONCLUSION: AT1 R-Ab showed
      no independent prognostic role in TG in this pilot analysis.

PMID- 30218594
TI  - Effects of aloe emodin on U87MG glioblastoma cell growth: In vitro and in vivo
      study.
AB  - Glioblastoma, the most aggressive and malignant form of glioma, appears to be
      resistant to various chemotherapeutic agents. Hence other approaches have been
      investigated to target more pathways involved in glioblastoma development and
      progression. Here we investigate the anticancer effect of Aloe-Emodin (AE), an
      anthraquinone compound presents in the leaves of Aloe arborescens, on human
      glioblastoma cell line U87MG. U87MG were treated with various concentrations of
      AE (20 and 40 MUM) for different times (24, 48, and 72 hr). Cell growth was
      monitored by daily cell count after treatments. Growth analysis showed that AE
      significantly decrease proliferation of U87MG in a time and dose dependent
      manner. FACS analysis demonstrates a block of cell cycle in S and G2/M phase. AE
      probably induced also apoptosis by releasing of apoptosis-inducing factor: PARP
      and Lamin activation leading to nuclear shrinkage. In addition, exposure of U87MG
      to AE reduced pAKT phosphorylation. AE inhibition of U87MG growth is a result of
      more mechanism together. Here we report that AE has a specific growth inhibition
      on U87MG also in in vivo. The growth of U87MG, subcutaneously injected in nude
      mice with severe combined immunodeficiency, is inhibited without any appreciable
      toxic effects on the animals after AE treatment. AE might represent a
      conceptually new lead antitumor adjuvant drug.

PMID- 30218595
TI  - Kefir micro-organisms: their role in grain assembly and health properties of
      fermented milk.
AB  - Kefir is a homemade viscous and slightly effervescent beverage obtained by milk
      fermentation with kefir grains, which are built up by a complex community of
      lactic acid and acetic acid bacteria and yeasts confined in a matrix of proteins
      and polysaccharides. The present review summarizes the role of kefir micro
      organisms in grain assembly and in the beneficial properties attributed to kefir.
      The use of both culture-dependent and independent methods has made possible to
      determine the micro-organisms that constitute this ecosystem. Kefir consumption
      has been associated with a wide range of functional and probiotic properties that
      could be attributed to the micro-organisms present in kefir and/or to the
      metabolites synthetized by them during milk fermentation. In this context, the
      role of micro-organisms in kefir health promoting properties is discussed with
      particular attention to the contribution of yeast as well as bioactive
      metabolites such as lactic and acetic acid, exopolysaccharides and bioactive
      peptides. Even though many advances on the knowledge of this ancient fermented
      milk have been made, further studies are necessary to elucidate the complex
      nature of the kefir ecosystem.

PMID- 30218596
TI  - Liver Transplantation for Severe Alcoholic Hepatitis: Where Are We Now?

PMID- 30218597
TI  - Interplay Between Reversible Phosphorylation and Irreversible Adp-Ribosylation of
      Eukaryotic Translation Elongation Factor 2.
AB  - The functionality of eukaryotic translation elongation factor 2 (eEF2) is
      modulated by phosphorylation, eEF2 is simultaneously the molecular target of ADP
      ribosylating toxins. We analyzed the interplay between phosphorylation and
      diphthamide-dependent ADPribosylation. Phosphorylation does not require
      diphthamide, eEF2 without it still becomes phosphorylated. ADP-ribosylation not
      only modifies the H715 diphthamide but also inhibits phosphorylation of S595
      located in proximity to H715, and stimulates phosphorylation of T56. S595 can be
      phosphorylated by CDK2 and CDK1 which affects EEF2K-mediated T56-
      phosphorylation. Thus, ADP-ribosylation and S595-phosphorylation by kinases occur
      within the same vicinity and both trigger T56-phosphorylation. Diphthamide is
      surface-accessible permitting access to ADP-ribosylating enzymes, the adjacent
      S595 side chain extends into the interior. This orientation is incompatible with
      phosphorylation, neither allowing kinase access nor phosphate attachment. S595
      phosphorylation must therefore be accompanied by structural alterations affecting
      the interface to ADP-ribosylating toxins. In agreement with that, replacement of
      S595 with Ala, Glu or Asp prevents ADP-ribosylation. Phosphorylation (starvation)
      as well as ADP-ribosylation (toxins) inhibit protein synthesis, both affect the
      S595/H715 region of eEF2, both trigger T57-phosphorylation eliciting similar
      transcriptional responses. Phosphorylation is short lived while ADP-ribosylation
      is stable. Thus, phosphorylation of the S595/H715 'modifier region' triggers
      transient interruption of translation while ADP-ribosylation arrests
      irreversibly.

PMID- 30218598
TI  - Algorithms for mapping kidney tissue oxygenation during normothermic machine
      perfusion using hyperspectral imaging.
AB  - The lack of donor grafts is a severe problem in transplantation medicine. Hence,
      the improved preservation of existing and the usage of organs that were deemed
      untransplantable is as urgent as ever. The development of novel preservation
      techniques has come into focus. A promising alternative to traditional cold
      storage is normothermic machine perfusion (NMP), which provides the benefit of
      improving the organs' viability and of assessing the organs' status under
      physiological conditions. For this purpose, methods for evaluating organ
      parameters have yet to be developed. In a previous study, we determined the
      tissue oxygen saturation (StO2) of kidneys during NMP with hyperspectral imaging
      (HSI) based on a discrete wavelength (DW) algorithm. The aim of the current study
      was to identify a more accurate algorithm for StO2 calculation. A literature
      search revealed three candidates to test: a DW algorithm and two full spectral
      algorithms - area under a curve and partial least square regression (PLSR). After
      obtaining suitable calibration data to train each algorithm, they were evaluated
      during NMP. The wavelength range from 590 to 800 nm was found to be appropriate
      for analyzing StO2 of kidneys during NMP. The PLSR method shows good results in
      analyzing the tissues' oxygen status in perfusion experiments.

PMID- 30218599
TI  - NUMBER: standardized reference intervals in the Netherlands using a 'big data'
      approach.
AB  - Background External quality assessment (EQA) programs for general chemistry tests
      have evolved from between laboratory comparison programs to trueness verification
      surveys. In the Netherlands, the implementation of such programs has reduced
      inter-laboratory variation for electrolytes, substrates and enzymes. This allows
      for national and metrological traceable reference intervals, but these are still
      lacking. We have initiated a national endeavor named NUMBER (Nederlandse UniforMe
      Beslisgrenzen En Referentie-intervallen) to set up a sustainable system for the
      determination of standardized reference intervals in the Netherlands. Methods We
      used an evidence-based 'big-data' approach to deduce reference intervals using
      millions of test results from patients visiting general practitioners from
      clinical laboratory databases. We selected 21 medical tests which are either
      traceable to SI or have Joint Committee for Traceability in Laboratory Medicine
      (JCTLM)-listed reference materials and/or reference methods. Per laboratory, per
      test, outliers were excluded, data were transformed to a normal distribution (if
      necessary), and means and standard deviations (SDs) were calculated. Then,
      average means and SDs per test were calculated to generate pooled (mean+/-2 SD)
      reference intervals. Results were discussed in expert meetings. Results Sixteen
      carefully selected clinical laboratories across the country provided anonymous
      test results (n=7,574,327). During three expert meetings, participants found
      consensus about calculated reference intervals for 18 tests and necessary
      partitioning in subcategories, based on sex, age, matrix and/or method. For two
      tests further evaluation of the reference interval and the study population were
      considered necessary. For glucose, the working group advised to adopt the
      clinical decision limit. Conclusions Using a 'big-data' approach we were able to
      determine traceable reference intervals for 18 general chemistry tests.
      Nationwide implementation of these established reference intervals has the
      potential to improve unequivocal interpretation of test results, thereby reducing
      patient harm.

PMID- 30218600
TI  - Defining reference intervals for a serum growth differentiation factor-15 (GDF
      15) assay in a Caucasian population and its potential utility in diabetic kidney
      disease (DKD).
AB  - BACKGROUND: Growth differentiation factor-15 (GDF-15), a stress responsive
      cytokine, is a promising biomarker of renal functional decline in diabetic kidney
      disease (DKD). This study aimed primarily to establish normative data and
      secondarily to evaluate the potential utility of GDF-15 in DKD using Roche
      Diagnostics electrochemiluminescence immunoassay (ECLIA) in an Irish Caucasian
      population. METHODS: Following informed consent, 188 healthy volunteers and 128
      participants with diabetes (72 with and 56 without DKD) were recruited to a cross
      sectional study. Baseline demographics, anthropometric measurements and
      laboratory measurements were recorded. Blood for GDF-15 measurement was collected
      into plain specimen tubes kept at room temperature and processed (centrifugation,
      separation of serum, freezing at -80  degrees C) within 1 h of phlebotomy pending
      batch analyses. Reference intervals were determined using the 2.5th and 97.5th
      percentiles for serum GDF-15 concentration. RESULTS: Of 188 healthy participants,
      63 failed to meet study inclusion criteria. The reference interval for serum GDF
      15 was 399 ng/L (90% confidence interval [CI]: 399-399) - 1335 ng/L (90% CI: 1152
      1445). Receiver operator characteristics (ROC) curve analysis for DKD determined
      the area under the ROC curve to be 0.931 (95% CI: 0.893-0.959; p<0.001). The
      optimum GDF-15 cutoff for predicting DKD was >1136 ng/L providing a diagnostic
      sensitivity and specificity of 94.4% and 79%, respectively, and positive
      likelihood ratio of 4.5:1 (95% CI: 3.4-6.0). CONCLUSIONS: The reference interval
      for serum GDF-15 in a healthy Irish Caucasian population using Roche Diagnostics
      ECLIA was established and a preliminary determination of the potential of GDF-15
      as a screening test for DKD was made. Further prospective validation with a
      larger DKD cohort will be required before the cutoff presented here is
      recommended for clinical use.

PMID- 30218601
TI  - Preanalytical stability of [-2]proPSA in whole blood stored at room temperature
      before separation of serum and plasma: implications to Phi determination.
AB  - Background [-2]proPSA seems to outperform free/total prostate-specific antigen
      (PSA) ratio in prostate cancer diagnosis. However, [-2]proPSA stability remains
      an underestimated issue. We examined [-2]proPSA stability over time in whole
      blood before separation of serum and plasma and its implications for prostate
      health index (Phi) determination. Total PSA (tPSA) and free PSA (fPSA)
      stabilities were also assessed. Methods Blood was drawn from 26 patients and
      separated in two tubes for plasma (K2EDTA and K2EDTA plus protease inhibitors -
      P100) and one for serum (clot activator plus gel separator). Tubes were stored at
      room temperature before centrifugation 1, 3 and 5 h for serum and EDTA plasma or
      1 and 5 h for P100 plasma. To investigate the influence of gel separator on
      markers' stability, blood was collected from 10 patients in three types of tubes
      to obtain serum: tubes with clot activator plus gel separator, with silica
      particles or glass tubes. Biomarkers were assayed with chemiluminescent
      immunoassays. Results [-2]proPSA and Phi levels significantly and progressively
      increased over time in serum (+4.81% and +8.2% at 3 h; +12.03% and +14.91% at 5
      h, respectively, vs. 1 h; p<0.001). Conversely, [-2]proPSA levels did not change
      in plasma (EDTA or P100). tPSA levels did not change over time in serum or
      plasma, whereas fPSA decreased in serum. All markers were higher in plasma than
      in serum at any time point. This difference did not seem to be attributable to
      the use of gel for serum preparation. Conclusions EDTA prevented spurious in
      vitro modifications in PSA-related isoforms, confirming that a stabilized blood
      sample is a prerequisite for [-2]proPSA measurement and Phi determination.

PMID- 30218602
TI  - A patient focused relationship for specialists in laboratory medicine.
AB  - Technological change is driving individualized healthcare delivery including
      laboratory medicine. Ensuring patients gain from their empowerment it is
      essential that they access data that enables them to utilize reliable
      information. The potential difficulties of comprehension, information retention
      and imperfect modes of communication can significantly impair utilization of
      information by patients. Support for understanding and decision-making needs to
      be clinically competent and integrated within the healthcare team. Specialists in
      laboratory medicine are well placed to undertake such a role, the issues around
      this are explored and proposals for better direct engagement with patients made.

PMID- 30218604
TI  - Identification of Missing Carbon Fixation Enzymes as Potential Drug Targets in
      Mycobacterium Tuberculosis.
AB  - Metabolic adaptation to the host environment has been recognized as an essential
      mechanism of pathogenicity and the growth of Mycobacterium tuberculosis (Mtb) in
      the lungs for decades. The Mtb uses CO2 as a source of carbon during the dormant
      or non-replicative state. However, there is a lack of biochemical knowledge of
      its metabolic networks. In this study, we investigated the CO2 fixation pathways
      (such as ko00710 and ko00720) most likely involved in the energy production and
      conversion of CO2 in Mtb. Extensive pathway evaluation of 23 completely sequenced
      strains of Mtb confirmed the existence of a complete list of genes encoding the
      relevant enzymes of the reductive tricarboxylic acid (rTCA) cycle. This provides
      the evidence that an rTCA cycle may function to fix CO2 in this bacterium. We
      also proposed that as CO2 is plentiful in the lungs, inhibition of CO2 fixation
      pathways (by targeting the relevant CO2 fixation enzymes) could be used in the
      expansion of new drugs against the dormant Mtb. In support of the suggested
      hypothesis, the CO2 fixation enzymes were confirmed as a potential drug target by
      analyzing a number of attributes necessary to be a good bacterial target.

PMID- 30218603
TI  - The influence of thyroid disorders on bone density and biochemical markers of
      bone metabolism.
AB  - Background Thyroid dysfunction, predominantly hyperthyroidism, has been
      previously linked to impaired bone mass density (BMD) and increased risk of
      fractures. On the other hand, data in the field of hypothyroidism (HT) are
      missing. The purpose of the present study was to investigate the impact of
      thyroid disorders on bone density serum and urine calcium (Ca) and phosphate (P)
      as well as serum osteocalcin and alkaline phosphatase and urine hydroxyproline in
      a series of post-menopausal women. Materials and methods The study was conducted
      in the Reproductive Endocrinology Outpatient Clinic of our hospital. A
      consecutive series of post-menopausal women was included, after excluding
      patients under hormone treatment (including levothyroxine supplementation) and
      those who received raloxifene, tamoxifen or tibolone during the study period as
      well as those who received treatment during the previous 12 months were excluded
      from the present study. Results Overall, 188 women were included in the present
      study. Among them, 143 women had normal thyroid function, 32 women had
      hyperthyroidism and 13 women had HT. Correlation of thyroid function indices with
      osteoporosis indices revealed statistically significant correlations between
      thyroxine (T4) and free triiodothyronine (T3) with T-, Z-scores and BMD. Logistic
      regression analysis concerning the impact of HT and hyperthyroidism on T-score, Z
      score and bone mass density revealed that both pathological entities negatively
      affect bone health (p < 0.05). Conclusion The findings of our study suggest that
      not only hyperthyroidism, but also HT negatively affects BMD. Future studies
      should investigate this association and corroborate our findings.

PMID- 30218606
TI  - Effect of dual tocolysis with fenoterol and atosiban in human myometrium.
AB  - Objectives To measure the tocolytic effect of the combination of the oxytocin
      receptor antagonist atosiban with the beta-mimetic agent fenoterol on human
      myometrium of pregnant women. Methods An in vitro study of contractility in human
      myometrium at the Laboratory of the Department of Obstetrics, University Hospital
      of Zurich, Switzerland, was performed. Thirty-six human myometrial biopsies were
      obtained during elective caesarean sections of singleton pregnancies at term.
      Tissue samples were exposed to atosiban, fenoterol and the combination of
      atosiban with fenoterol. Contractility was measured as area under the curve
      during 30 min of spontaneous contractions. The effect of treatment was expressed
      as the percentage of change from basal activity during 30 min of exposure.
      Differences were calculated using a paired Wilcoxon signed-rank test. An additive
      effect of dual tocolysis was assumed when no significant difference was detected
      between the observed and expected inhibition of dual tocolysis. When inhibition
      was greater or lower than expected, the dual combination was characterised as
      "synergistic" or "antagonistic", respectively. Results Atosiban and fenoterol
      alone suppressed contractions by a median of 43.2% and 29.8%, respectively. The
      combination of atosiban plus fenoterol was measured at a level of 67.3%
      inhibition. There was no significant difference in the expected (63.2%) and
      observed inhibition effect of dual tocolysis (P=0.945). Conclusions This study
      demonstrated an additive effect of dual tocolysis of atosiban and fenoterol on
      human myometrium in vitro, but no synergistic or antagonistic effect.

PMID- 30218605
TI  - Modeling and Simulating the Aerobic Carbon Metabolism of a Green Microalga Using
      Petri Nets and New Concepts of VANESA.
AB  - In this work we present new concepts of VANESA, a tool for modeling and
      simulation in systems biology. We provide a convenient way to handle mathematical
      expressions and take physical units into account. Simulation and result
      management has been improved, and syntax and consistency checks, based on
      physical units, reduce modeling errors. As a proof of concept, essential
      components of the aerobic carbon metabolism of the green microalga Chlamydomonas
      reinhardtii are modeled and simulated. The modeling process is based on xHPN
      Petri net formalism and simulation is performed with OpenModelica, a powerful
      environment and compiler for Modelica. VANESA, as well as OpenModelica, is open
      source, free-of-charge for non-commercial use, and is available at:
      http://agbi.techfak.uni-bielefeld.de/vanesa.

PMID- 30218607
TI  - The diagnostic value of a detailed first trimester anomaly scan in fetuses with
      increased nuchal translucency thickness.
AB  - Objectives To assess the diagnostic value of an early anomaly scan in fetuses
      with increased nuchal translucency (NT) in the prediction of aneuploidy. Methods
      In this study we analyzed the data of pregnant women obtained at their first
      trimester screening in our unit. The detailed examination routinely includes
      measurement of NT and a scan for anatomical defects. For fetuses with an NT>=3.5
      mm, the diagnostic power of early major sonographic findings (MSF) regarding
      abnormal karyotype was calculated. Results A total of 7352 first trimester
      examinations were screened. Two hundred and twenty-two fetuses with an NT>=3.5 mm
      were analyzed. The median gestational age was 12.5 weeks (range 11.0-14.6) and
      the median NT was 5.1 mm (range 3.5-15.3). MSF were detected in 51.8% of fetuses
      with increased NT. Among 115 fetuses with MSF, 91 were aneuploid, yielding a
      positive predictive value for aneuploidy of 79.1%. In the absence of MSF, the
      negative predictive value was 70.1%. The presence of MSF was significantly
      predictive for aneuploidy both in bivariate and multivariate regression analysis.
      Conclusions Our study underlines the importance of a detailed anatomical
      ultrasound in fetuses with increased NT, as MSF occurred frequently. However, the
      diagnostic value of MSF regarding aneuploidies appears to be moderate.

PMID- 30218609
TI  - Minute duodenal metastasis in a patient with thoracic esophageal squamous cell
      carcinoma successfully treated with chemoradiotherapy.

PMID- 30218608
TI  - N-Methyl Pyrrolidone (NMP) Alleviates Lipopolysaccharide (LPS)-Induced
      Inflammatory Injury in Articular Chondrocytes.
AB  - BACKGROUND Studies on the chondrocyte inflammatory injury are very important for
      understanding the pathogenesis and clinical treatment of osteoarthritis (OA).
      Evidence suggests that N-methyl pyrrolidone (NMP) may be used as an adjuvant
      therapy alongside established methods of OA treatment. This study investigated
      the effect of NMP on chondrocyte inflammatory injury and explored the underlying
      molecular mechanism. MATERIAL AND METHODS To mimic the inflammatory injury in
      vitro, the articular chondrocyte line ATDC5 was simulated with lipopolysaccharide
      (LPS). ATDC5 cells were treated with various concentrations of NMP (0, 5, and 10
      nM). Cell viability was measured using CCK-8 assay; cell apoptosis was detected
      using FCM; related protein and mRNA expressions were determined using Western
      blot assay and qRT-PCR assay; and inflammatory factors (tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8) productions were measured by
      performing ELISA assay. RESULTS The results showed that LPS simulation repressed
      ATDC5 cell viability, prompted cell apoptosis, and enhanced the secretion of
      inflammatory factors. NMP treatment reduced inflammatory injury induced by LPS in
      a dose-dependent manner. Furthermore, NMP inhibited the activation of JNK and p38
      pathways. In addition, inhibition of NF-kappaB activation was observed following
      NMP treatment. CONCLUSIONS NMP prevents inflammatory reaction of articular
      chondrocytes via repressing the MAPK/NF-kB pathway. Our findings provide a
      promising therapeutic agent for OA treatment.

PMID- 30218610
TI  - Thrombectomy in posterior circulation stroke: differences in procedures and
      outcome compared to anterior circulation stroke in the prospective multicentre
      REVASK registry.
AB  - BACKGROUND AND PURPOSE: In contrast to anterior circulation stroke (ACS), there
      is no evidence from randomized trials that mechanical thrombectomy (MT) with
      modern stent retrievers or thromboaspiration is safe and effective in posterior
      circulation stroke (PCS). METHODS: The present analysis was based on the
      prospective multicentre Registry on Revascularization in Ischemic Stroke Patients
      (REVASK) in Germany. Demographic data, periprocedural times and complications,
      recanalization rates, and functional outcome at discharge and after 3 months were
      compared between 139 consecutive patients with PCS (84.9% basilar artery, 16.5%
      vertebral artery and 4.3% posterior cerebral artery occlusion) and 961 patients
      with ACS treated with MT. RESULTS: Compared to ACS, PCS patients were
      significantly younger (65 vs. 69 years, P = 0.021) and had a lower median
      National Institutes of Health Stroke Scale (NIHSS) score at baseline (12 vs. 15,
      P = 0.024). Patients with PCS had a significantly longer time delay between
      symptom onset and both start and end of the MT procedure. Successful
      recanalization and thrombectomy passes did not significantly differ between the
      two groups. No symptomatic intracranial haemorrhage occurred in PCS compared to
      3% in ACS (P = 0.010). The median NIHSS score at discharge was 3 in PCS and 4 in
      ACS. Favourable functional outcome at 3 months (modified Rankin Scale 0-2 38.0%
      vs. 42.6%, P = 0.392) and mortality (33.7% vs. 30.8%, P = 0.539) did not differ
      significantly between PCS and ACS. CONCLUSIONS: The study suggests that MT in PCS
      shows a lower risk of symptomatic intracranial haemorrhage and similar
      effectiveness compared to ACS. PCS patients also seem to benefit from MT started
      beyond 6 h after symptom onset.

PMID- 30218611
TI  - Verbal working memory modulates afferent circuits in motor cortex.
AB  - Verbal instruction and strategies informed by declarative memory are key to
      performance and acquisition of skilled actions. We previously demonstrated that
      anatomically distinct sensory-motor inputs converging on the corticospinal
      neurons of motor cortex are differentially sensitive to visual attention load.
      However, how loading of working memory shapes afferent input to motor cortex is
      unknown. This study used short-latency afferent inhibition (SAI) to probe the
      effect of verbal working memory upon anatomically distinct afferent circuits
      converging on corticospinal neurons in the motor cortex. SAI was elicited by
      preceding a suprathreshold transcranial magnetic stimulus (TMS) with electrical
      stimulation of the median nerve at the wrist while participants mentally
      rehearsed a two- or six-digit numeric memory set. To isolate different afferent
      intracortical circuits in motor cortex SAI was elicited, using TMS involving
      posterior-anterior (PA) or anterior-posterior (AP) monophasic current. Both PA
      and AP SAI were significantly reduced during maintenance of the six-digit
      compared to two-digit memory set. The generalized effect of working memory across
      anatomically distinct circuits converging upon corticospinal neurons in motor
      cortex is in contrast to the specific sensitivity of AP SAI to increased
      attention load. The common response across the PA and AP SAI circuits to
      increased working memory load may reflect an indiscriminate perisomatic mechanism
      involved in the voluntary facilitation of desired and/or suppression of unwanted
      actions during action selection or response conflict.

PMID- 30218612
TI  - Mechanisms of pathogenic effects of eosinophil cationic protein and eosinophil
      derived neurotoxin on human keratinocytes.
AB  - Cutaneous deposition of eosinophil degranulation proteins is a major feature of
      eosinophil-rich cutaneous diseases including bullous pemphigoid (BP). We sought
      to better understand the effect of two of these proteins - eosinophil cationic
      protein (ECP) and eosinophil-derived neurotoxin (EDN), on human keratinocytes
      using the Het-1A cell line. To evaluate expression of key cytokines and
      chemokines observed in BP as well as metal metalloprotease 9 (MMP9), we performed
      qPCR and in-cell Western assays on cells treated with either ECP or EDN. We
      further evaluated the effect of ECP and EDN on keratinocyte survival, generation
      of reactive oxygen species (ROS) and apoptosis. Lastly, we assessed ECP and EDN's
      ability to induce keratinocyte detachment from provisional matrix. Treatment of
      keratinocytes with ECP and EDN resulted in significant increases in IL-5, eotaxin
      1 and CCL5 (RANTES) expression at both mRNA and protein levels, but not IL-17 or
      IL-31. ECP and EDN also upregulate MMP9 production. Inhibiting MMP9, we confirmed
      that keratinocyte expression of IL-5, eotaxin-1 and RANTES was independent from
      MMP9. Both ECP and EDN were cytotoxic to keratinocytes, inducing ROS formation
      and apoptosis through a mitochondrion-dependent pathway as evidenced by results
      of terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) and
      cytochrome c release assays, respectively. ECP but not EDN led to significant
      keratinocyte detachment from provisional matrix. These findings demonstrate that
      the pathogenic effects of ECP and EDN in BP may result from their direct action
      on keratinocytes, and as such may became a target for future therapies in
      eosinophil-rich cutaneous diseases.

PMID- 30218613
TI  - Determinants of maximal whole-body fat oxidation in elite cross-country skiers:
      Role of skeletal muscle mitochondria.
AB  - Elite endurance athletes possess a high capacity for whole-body maximal fat
      oxidation (MFO). The aim was to investigate the determinants of a high MFO in
      endurance athletes. The hypotheses were that augmented MFO in endurance athletes
      is related to concomitantly increments of skeletal muscle mitochondrial volume
      density (MitoVD ) and mitochondrial fatty acid oxidation (FAOp ), that is,
      quantitative mitochondrial adaptations as well as intrinsic FAOp per
      mitochondria, that is, qualitative adaptations. Eight competitive male cross
      country skiers and eight untrained controls were compared in the study. A graded
      exercise test was performed to determine MFO, the intensity where MFO occurs
      (FatMax ), and VO2Max . Skeletal muscle biopsies were obtained to determine
      MitoVD (electron microscopy), FAOp , and OXPHOSp (high-resolution respirometry).
      The following were higher (P < 0.05) in endurance athletes compared to controls:
      MFO (mean [95% confidence intervals]) (0.60 g/min [0.50-0.70] vs 0.32 [0.24
      0.39]), FatMax (46% VO2Max [44-47] vs 35 [34-37]), VO2Max (71 mL/min/kg [69-72]
      vs 48 [47-49]), MitoVD (7.8% [7.2-8.5] vs 6.0 [5.3-6.8]), FAOp (34 pmol/s/mg
      muscle ww [27-40] vs 21 [17-25]), and OXPHOSp (108 pmol/s/mg muscle ww [104-112]
      vs 69 [68-71]). Intrinsic FAOp (4.0 pmol/s/mg muscle w.w/MitoVD [2.7-5.3] vs 3.3
      [2.7-3.9]) and OXPHOSp (14 pmol/s/mg muscle ww/MitoVD [13-15] vs 11 [10-13])
      were, however, similar in the endurance athletes and untrained controls. MFO and
      MitoVD correlated (r2  = 0.504, P < 0.05) in the endurance athletes. A strong
      correlation between MitoVD and MFO suggests that expansion of MitoVD might be
      rate-limiting for MFO in the endurance athletes. In contrast, intrinsic
      mitochondrial changes were not associated with augmented MFO.

PMID- 30218615
TI  - No clinical impact of HCV RNA determination at the end of treatment in patients
      receiving directly acting antivirals.

PMID- 30218614
TI  - Can participants predict where ambulance-requiring cases occur at a half
      marathon?
AB  - OBJECTIVES: Despite endurance races leading to a substantial number of ambulance
      requiring cases (ARC), little is known regarding where they occur, meaning that
      knowing where to place medical teams, ambulance pick-up points, etc, is
      difficult. This article investigates whether the location of ARCs can be
      identified by race participants. METHODS: Using the world's largest half marathon
      (Gothenburg half marathon) as a case, 237 runners were asked, post-race, to mark
      on a map which geographical point of the race was most exhausting. Using the
      level of agreement tests, these geographical points were then compared with the
      GPS positions of ARCs. RESULTS: According to the level of agreement tests, the
      most exhausting positions (MEP), as identified by participants, seem to be highly
      correlated to the location of ARCs. This study can also show that ambulance
      requiring cases seem to be more prevalent towards the end of the race and in
      uphill sections. CONCLUSIONS: By asking participants where they found the race
      most exhausting it seems possible to identify high-risk places for an ARC. From a
      practical perspective, using this method could considerably increase the safety
      of competitors as well as improving the cost-effectiveness of safety
      interventions at endurance races. Further studies are needed to understand the
      specific risk factors of the high-risk areas as well as characteristics of
      collapsed runners.

PMID- 30218616
TI  - Placental thickness in the lower uterine segment and invasive placentation: Will
      the promise live up?

PMID- 30218617
TI  - Cystatin C measurement leads to lower metformin dosage in elderly type 2 diabetic
      patients.
AB  - The aim of this study was to provide evidence for the hypothesis that estimated
      glomerular filtration rate from serum Cystatin C (eGFRcys) is better to be
      determined for all elderly type 2 diabetes mellitus (T2DM) patients based on
      eGFRcys upward and downward reclassification rate for hypothetical metformin dose
      reduction by eGFRcys at the GFR decision point of 45 mL/min/1.73 m2 . A total of
      265 consecutive T2DM elderly patients (age range 65-91 years) from outpatient
      diabetic clinic were included in the study. The Kidney Disease Improving Global
      Outcomes (KDIGO) guidelines for metformin dosing were strictly followed.
      Estimated glomerular filtration rate from serum creatinine (eGFRcrea) led to
      results of metformin eligibility. Each of the results of eGFRcrea-based
      eligibility was further compared to eGFRcys-based eligibility. Creatinine was
      measured by enzymatic method standardized against international reference
      material SRM 967. Cystatin C was determined by method traceable to DA ERM 471
      international standard. eGFRcrea and eGFRcys were calculated according to Chronic
      Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. A downward
      reclassification rate was higher than upward reclassification rate (31 vs 3,
      respectively; P < 0.0001). The median (IQR) eGFRcrea was higher than eGFRcys (73
      (58-85) vs 63 (50-75) mL/min/1.73 m2 , respectively; P < 0.0001). eGFRcys
      reclassified significant proportion of patients with T2DM from metformin eligible
      CKD stages to less or non-eligible stages. The downward reclassification was more
      frequent in patients older than 80 years (P < 0.01). Cystatin C-based eGFR
      selects more complicated patients, where lower doses of metformin are possibly
      advisable. We recommend calculating both eGFRcrea and eGFRcys for metformin
      dosing in elderly patients with T2DM.

PMID- 30218618
TI  - Chronic nicotine administration restores brain region specific upregulation of
      oxytocin receptor binding levels in a G72 mouse model of schizophrenia.
AB  - Nicotine dependence and schizophrenia are two mental health disorders with
      remarkably high comorbidity. Cigarette smoking is particularly prevalent amongst
      schizophrenic patients and it is hypothesised to comprise a form of self
      medication for relieving cognitive deficits in these patients. Emerging evidence
      suggests a role of the neurohypophysial peptide oxytocin in the modulation of
      drug addiction, as well as schizophrenia symptomology; however, the underlying
      mechanism remains unclear. Therefore, we sought to investigate the effects of
      chronic nicotine administration on oxytocin receptor (OTR) binding in the brain
      of a transgenic mouse model of schizophrenia that carries a bacterial artificial
      chromosome of the human G72/G30 locus (G72Tg). Female wild-type (WT) and
      heterozygous G72 transgenic CD-1 mice were treated with a chronic nicotine
      regimen (24 mg/kg/day, osmotic minipumps for 14 days) and quantitative
      autoradiographic mapping of oxytocin receptors was carried out in brains of these
      animals. OTR binding levels were higher in the cingulate cortex (CgCx), nucleus
      accumbens (Acb), and central amygdala (CeA) of saline treated G72Tg mice compared
      to WT control mice. Chronic nicotine administration reversed this upregulation in
      the CgCx and CeA. Interestingly, chronic nicotine administration induced an
      increase in OTR binding in the CeA of solely WT mice. These results indicate that
      nicotine administration normalises the dysregulated central oxytocinergic system
      of this mouse model of schizophrenia and may contribute towards nicotine's
      ability to modulate cognitive deficits which are common symptoms of
      schizophrenia.

PMID- 30218619
TI  - Response to Nunes and colleagues letter: The data do not seem to support the
      effect of stretch training in increasing MT.

PMID- 30218620
TI  - Profiles of women in science: Nora Volkow, Director of the National Institute of
      Drug Abuse, Bethesda MD.

PMID- 30218621
TI  - Extrahepatic autoimmune diseases in patients with autoimmune hepatitis and their
      relatives: A Danish nationwide cohort study.
AB  - BACKGROUND & AIMS: It is widely accepted that patients with autoimmune hepatitis
      have an increased prevalence of extrahepatic autoimmune diseases. It is believed
      that the patients' relatives share this trait, but it has not been studied in a
      satisfactory setting. We conducted a nationwide registry-based cohort study on
      this issue. METHODS: From Danish healthcare registries 1994-2015, we included
      2745 patients with autoimmune hepatitis, 17 812 of their first- and second-degree
      relatives and 27 450 general population controls matched with the patients for
      sex and age. We compared the sex- and age-specific prevalence of extrahepatic
      autoimmune diseases between the patients with autoimmune hepatitis, their
      relatives and the controls. We computed the prevalence ratio as a measure of the
      relative prevalence, using the controls as reference group. RESULTS: In the
      patients with autoimmune hepatitis, the prevalence ratio of extrahepatic
      autoimmune diseases ranged from 7 to 10 until age 30 years (prevalence ratio at
      age 20 = 9.92; 95% confidence interval 6.21-15.83), after which it gradually
      decreased to about 2 (prevalence ratio at age 80 = 2.37; 95% confidence interval
      1.89-3.00). Neither first- nor second-degree relatives had an increased
      prevalence of extrahepatic autoimmune diseases (prevalence ratio for relatives at
      age 20 = 1.11; 95% confidence interval 0.72-1.70; prevalence ratio at age 80 =
      0.96; 95% confidence interval 0.70-1.31). CONCLUSIONS: Danish patients with
      autoimmune hepatitis were highly prone to extrahepatic autoimmune diseases, but
      their relatives were not.

PMID- 30218622
TI  - Clinicocytopathological spectrum, including uncommon forms, of nine cases of
      chordomas with immunohistochemical results, including brachyury immunostaining: A
      single institutional experience.
AB  - OBJECTIVES: To present clinical and cytopathological features of nine cases of
      chordomas, diagnosed over 9 years and confirmed by brachyury (T) immunostaining.
      METHODS: Conventional cytological smears, stained with Papanicolaou and May
      Grunwald Giemsa, along with corresponding histopathological (n = 8) and
      immunostained sections (n = 8) were reviewed. Immunohistochemical staining was
      performed on tissue sections by polymer detection technique. RESULTS: Nine
      tumours occurred in seven males and two females, with age ranging from 36 to 72
      years (average = 58.7), in the sacrum (seven) and spine (two). On fine needle
      aspiration cytology, five cases were either diagnosed with or diagnosed with a
      suggestion of a chordoma, while three cases were diagnosed with chordoma as a
      differential diagnosis. On review, smears were moderately cellular, comprising
      myxoid stroma (9/9), epithelioid cells (9/9), physaliphorous cells (8/9),
      including binucleation (7/9), prominent nucleolisation (2/9), pleomorphic cells
      (2/9) and intranuclear inclusions (3/9). Immunohistochemically, tumour cells
      expressed cytokeratin (4/4), pan cytokeratin (4/4), epithelial membrane antigen
      (8/8), S100 protein (6/8) and brachyury (8/8). Five patients underwent surgical
      excision, including two who underwent adjuvant radiotherapy (RT) and four
      patients who underwent RT. During follow-up (n = 8), a single patient developed
      recurrence and another presented with metastatic lesions. Finally, five patients
      were alive with disease (7-53 months); a single patient was free of disease (4
      months), and two patients died of disease; the latter cases displayed pleomorphic
      cells and intranuclear inclusions. CONCLUSIONS: Chordomas can be primarily
      diagnosed by fine needle aspiration cytology in a typical clinicoradiological
      setting with a combination of key cytomorphological features. Pleomorphic cells
      and intranuclear inclusions are associated with a relatively aggressive subtype.
      An exact diagnosis has treatment implications and requires confirmation by
      brachyury immunostaining.

PMID- 30218623
TI  - Contributions of nucleus accumbens dopamine to cognitive flexibility.
AB  - There is a compelling evidence that midbrain dopamine (DA) neurons and their
      projections to the ventral striatum provide a mechanism for motivating reward
      seeking behavior, and for utilizing information about unexpected reward
      prediction errors (RPEs) to guide behavior based on current, rather than
      historical, outcomes. When this mechanism is compromised in addictions, it may
      produce patterns of maladaptive behavior that remain obdurate in the face of
      contrary information and even adverse consequences. Nonetheless, DAergic
      contributions to performance on behavioral tasks that rely on the ability to
      flexibly update stimulus-reward relationships remains incompletly understood. In
      the current study, we used a discrimination and reversal paradigm to monitor
      subsecond DA release in mouse NAc core (NAc) using in vivo fast-scan cyclic
      voltammetry (FSCV). We observed post-choice elevations in phasic NAc DA release;
      however, increased DA transients were only evident during early reversal when
      mice made responses at the newly rewarded stimulus. Based on this finding, we
      used in vivo optogenetic (eNpHR) photosilencing and (Channelrhodopsin2 [ChR2])
      photostimulation to assess the effects of manipulating VTA-DAergic fibers in the
      NAc on reversal performance. Photosilencing the VTA -> NAc DAergic pathway during
      early reversal increased errors, while photostimulation did not demonstrably
      affect behavior. Taken together, these data provide additional evidence of the
      importance of NAc DA release as a neural substrate supporting adjustments in
      learned behavior after a switch in expected stimulus-reward contingencies. These
      findings have possible implications for furthering understanding the role of DA
      in persistent, maladaptive decision-making characterizing addictions.

PMID- 30218624
TI  - Illuminated night alters hippocampal gene expressions and induces depressive-like
      responses in diurnal corvids.
AB  - Artificial light at night induces circadian disruptions and causes cognitive
      impairment and mood disorders; yet very little is known about the neural and
      molecular correlates of these effects in diurnal animals. We manipulated the
      night environment and examined cellular and molecular changes in hippocampus, the
      brain region involved in cognition and mood, of Indian house crows (Corvus
      splendens) exposed to 12 hr light (150 lux): 12 hr darkness (0 lux). Diurnal
      corvids are an ideal model species with cognitive abilities at par with mammals.
      Dim light (6 lux) at night (dLAN) altered daily activity:rest pattern, reduced
      sleep, and induced depressive-like responses (decreased eating and self-grooming,
      self-mutilation, and reduced novel object exploration); return to an absolute
      dark night reversed these negative effects. dLAN suppressed nocturnal melatonin
      levels; however, diurnal corticosterone levels were unaffected. Concomitant
      reduction of immunoreactivity for DCX and BDNF suggested dLAN-induced suppression
      of hippocampal neurogenesis and compromised neuronal health. dLAN also negatively
      influenced hippocampal expression of genes associated with depressive-like
      responses (bdnf, il-1beta, tnfr1, nr4a2), but not of those associated with
      neuronal plasticity (egr1, creb, syngap, syn2, grin2a, grin2b), cellular
      oxidative stress (gst, sod3, cat1) and neuronal death (caspase2, caspase3,
      foxo3). Furthermore, we envisaged the role of BDNF and showed epigenetic
      modification of bdnf gene by decreased histone H3 acetylation and increased hdac4
      expression under dLAN. These results demonstrate transcriptional and epigenetic
      bases of dLAN-induced negative effects in diurnal crows, and provide insights
      into the risks of exposure to illuminated nights to animals including humans in
      an urban setting.

PMID- 30218625
TI  - Repurposing old drugs in oncology: Opportunities with clinical and regulatory
      challenges ahead.
AB  - WHAT IS KNOWN AND OBJECTIVE: In order to expedite the availability of drugs to
      treat cancers in a cost-effective manner, repurposing of old drugs for
      oncological indications is gathering momentum. Revolutionary advances in
      pharmacology and genomics have demonstrated many old drugs to have activity at
      novel antioncogenic pharmacological targets. We decided to investigate whether
      prospective studies support the promises of nonclinical and retrospective
      clinical studies on repurposing three old drugs, namely metformin, valproate and
      astemizole. METHODS: We conducted an extensive literature search through PubMed
      to gather representative nonclinical and retrospective clinical studies that
      investigated the potential repurposing of these three drugs for oncological
      indications. We then searched for prospective studies aimed at confirming the
      promises of retrospective data. RESULTS AND DISCUSSION: While evidence from
      nonclinical and retrospective clinical studies with these drugs appears highly
      promising, large scale prospective studies are either lacking or have failed to
      substantiate this promise. We provide a brief discussion of some of the
      challenges in repurposing. Principal challenges and obstacles relate to
      heterogeneity of cancers studied without considering their molecular signatures,
      trials with small sample size and short duration, failure consider issues of
      ethnicity of study population and effective antioncogenic doses of the drug
      studied. WHAT IS NEW AND CONCLUSION: Well-designed prospective studies
      demonstrating efficacy are required for repurposing old drugs for oncology
      indications, just as they are for new chemical entities for any indication. Early
      and ongoing interactions with regulatory authorities are invaluable. We outline a
      tentative framework for a structured approach to repurposing old drugs for novel
      indications in oncology.

PMID- 30218626
TI  - Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy
      Japanese and caucasian subjects.
AB  - As of March 2018, rasagiline is approved for the treatment of Parkinson disease
      in 55 countries including Japan. The present study evaluated the pharmacokinetics
      (PK) and safety of rasagiline in healthy Japanese and Caucasian subjects
      following single and multiple administrations of three rasagiline doses. In this
      double-blind, placebo-controlled study, 64 healthy subjects (32 Japanese and 32
      Caucasian) received either rasagiline (0.5, 1.0, or 2.0 mg) or placebo for 10
      days with PK sampling for single-dose administration on day 1 and for multiple
      administration on day 10. Regardless of administration schedule, rasagiline
      plasma concentrations and dose-related increases in exposure parameters were
      similar between Japanese and Caucasians. Rasagiline accumulation (2-fold for 0.5
      mg and 3-fold for 1.0 mg and 2.0 mg doses) following multiple administration was
      similar across the ethnic groups. Geometric mean ratios (GMR) comparing Japanese
      to Caucasians for AUC0-24 , Cmax and AUCinf following single administration were
      1.38, 1.17 and 1.38 for 0.5 mg; 1.22, 1.20 and 1.22 at 1.0 mg; and 1.02, 1.00 and
      1.02 at for 2.0 mg. GMR for AUCtau and Cmax,ss following multiple administration
      were 1.43 and 1.06 at 0.5 mg, 1.06 and 1.00 at 1.0 mg, and 1.09 and 1.07 at 2.0
      mg. Safety measures were unremarkable and similar between Caucasian and Japanese
      subjects. Comparable systemic exposure and safety parameters were demonstrated
      for rasagiline administered to healthy Japanese and Caucasian subjects.

PMID- 30218627
TI  - Dentofacial traumatic injuries: A survey of knowledge and attitudes among
      emergency medicine physicians in Turkey.
AB  - BACKGROUND/AIM: Emergency department (ED) visits for dental issues are mostly
      related to traumatic injuries. The knowledge of ED physicians about the diagnosis
      and treatment of dentofacial injuries is crucial for prognosis. The aim of this
      study was to evaluate the attitude and knowledge as well as education and self
      confidence levels of emergency medicine physicians in ED regarding the diagnosis
      and treatment of dentofacial traumatic injuries. MATERIAL AND METHODS: A total of
      109 emergency medicine physicians participated in the study. Participants were
      residents and specialists who attended a national emergency medicine symposium
      held in Turkey. A questionnaire was distributed during the symposium relating to
      general data about physicians, their attitudes, basic knowledge, and confidence
      levels which were believed to be indicative of their capabilities in managing of
      traumatic dental and maxillofacial injuries. RESULTS: The questionnaire was
      answered by 109 physicians who were general practitioners (11%), emergency
      medicine residents (56.8%), and emergency medicine specialists (32.2%). The most
      experienced group of physicians were emergency medicine specialists. Regardless
      of the physicians' titles, dentofacial trauma knowledge levels of ED physicians
      were found to be insufficient. Having a dentist in the family (P < 0.01), the
      duration of emergency service experience (P = 0.04), and the age of the
      physicians (P < 0.001) were significantly related to the knowledge level.
      CONCLUSIONS: The majority of ED physicians had low knowledge regarding the
      diagnosis and treatment of dentofacial traumatic injuries. There is a need for
      education during and after medical training for ED physicians to provide
      appropriate primary management of dentofacial trauma.

PMID- 30218628
TI  - Achieving the maximum by doing the minimum in the treatment of pilonidal sinus:
      where does evidence point?

PMID- 30218629
TI  - Anorexia nervosa or starvation?

PMID- 30218631
TI  - Martius flap for repair of complex rectovaginal fistulas - a video vignette.

PMID- 30218630
TI  - Improving the quality of maternity services in Nepal through accelerated
      implementation of essential interventions by healthcare professional
      associations.
AB  - OBJECTIVE: To assess whether the implementation of a package of activities
      through the joint action of three international healthcare professional
      associations (HCPAs) increased the use of essential interventions (EIs) for
      delivery and neonatal care. METHODS: A noncontrolled pre-intervention versus post
      intervention study was conducted from June 13 to December 13, 2016, among women
      older than 18 years of age, who had delivered at one of two urban tertiary
      hospitals in Nepal. RESULTS: The study included 9252 women. Minimal change was
      found after the implementation of EIs that were used frequently at baseline (e.g.
      social support during delivery in the emergency room, and promotion and support
      for early initiation of breastfeeding). By contrast, an increase was recorded for
      some EIs that had not been used regularly at baseline. For example, the rate of
      timely administration of prophylactic antibiotics before cesarean delivery
      increased from 0.0% (0/496) to 94.0% (409/435) at one hospital. Nonetheless, some
      EIs with low use at baseline did not show improvement after implementation (e.g.
      kangaroo mother care). CONCLUSION: The present study strengthened previous
      findings regarding the uptake of EIs following joint promotion by HCPAs in low
      income settings.

PMID- 30218632
TI  - Acceptability, effectiveness and safety of a Renew(r) anal insert in patients who
      have undergone restorative proctocolectomy with ileal pouch-anal anastomosis.
AB  - INTRODUCTION: Restorative proctocolectomy has gained acceptance in the surgical
      management of medically refractive ulcerative colitis and cancer prevention in
      familial adenomatous polyposis. Incontinence following restorative
      proctocolectomy occurs in up to 25% of patients overnight. The Renew(r) insert is
      an inert single-use device which acts as an anal plug. The aim of this study was
      to assess the acceptability, effectiveness and safety of the Renew(r) insert in
      patients who have undergone restorative proctocolectomy. The device has yet to be
      assessed in patients who have undergone restorative proctocolectomy. METHOD: This
      was a prospective study exploring the acceptability, effectiveness and safety of
      the Renew(r) insert in improving incontinence in patients who had undergone
      restorative proctocolectomy. A total of 15 patients with incontinence were asked
      to use the Renew(r) insert for 14 days following their standard care. The
      Incontinence Questionnaire-Bowels was used pre- and posttreatment to assess
      response and patients were asked to report the perceived acceptability,
      effectiveness and safety of the device at the end of the trial. RESULTS: The
      device was acceptable to 8/15 (53%) of patients and was effective in 6/15 (40%).
      Only 2/15 (13%) of patients raised any safety concerns, and these were minor. The
      device was associated with a significant reduction in night seepage (P = 0.034).
      CONCLUSION: In a small study, the Renew(r) insert can be both acceptable and
      effective and is also associated with few safety concerns. It is also associated
      with significant reductions in night-time seepage.

PMID- 30218633
TI  - OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA
      uptake and correlates with risk of malignancy.
AB  - BACKGROUND AND AIMS: Hepatobiliary phase (HBP) Gd-EOB-DTPA-enhanced magnetic
      resonance imaging (MRI) has increased the accuracy in differentiating focal
      nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). However, the ability
      of this technique to distinguish HCA subtypes remains controversial. The aim of
      this study was to investigate the expression of hepatocyte transporters
      (OATPB1/B3, MRP2, MRP3) in HCA subtypes, hence to understand their MRI signal
      intensity on HBP Gd-EOB-DTPA-enhanced MRI. METHODS: By means of
      immunohistochemistry (IHC), we scored the expression of OATPB1/B3, MRP2 and MRP3,
      in resected specimens of FNH (n = 40), subtyped HCA (n = 58) and HCA with focal
      malignant transformation (HCA-HCC, n = 4). Results were validated on a
      supplementary set of FNH (n = 6), subtyped HCA (n = 17) and HCA-HCC (n = 1) with
      Gd-EOB-DTPA MR images. RESULTS: All FNH showed a preserved expression of
      hepatocytes transporters. Beta-catenin-activated HCA (at highest risk of
      malignant transformation) and HCA-HCC were characterized by preserved/increased
      OATPB1/B3 expression (predictor of hyperintensity on HBP), as opposed to other
      HCA subtypes (P < 0.01) that mostly showed OATPB1/B3 absence (predictor of
      hypointensity on HBP). HCA-HCC showed an additional MRP3 overexpressed profile (P
      < 0.01). On HBP Gd-EOB-DTPA-enhanced MRI, FNH and HCA signal intensity reflected
      the profile predicted by their specific OATPB1/B3 tissue expression. The
      hyperintense vs hypointense HBP signal criterion was able to distinguish all
      higher risk HCA and HCA-HCC (100% accuracy). CONCLUSIONS: OATPB1/B3 and MRP3 IHC
      and signal intensity on HBP Gd-EOB-DTPA-enhanced MRI can help to stratify HCA
      according to their risk of malignant transformation.

PMID- 30218634
TI  - The vascular morphology of melanoma is related to Breslow index: An in vivo study
      with dynamic optical coherence tomography.
AB  - BACKGROUND: Malignant melanoma is an aggressive skin cancer, which can lead to
      metastasis development. Vascularization enhancement is fundamental for tumor
      growth, worsening the prognosis. Dynamic optical coherence tomography (D-OCT)
      enables the in vivo evaluation of vascular patterns in skin lesions. OBJECTIVE:
      In vivo evaluation of the melanoma vessel morphology by means of D-OCT and
      correlation with Breslow index. METHODS: Retrospective analysis of histologically
      proven melanomas, evaluated by D-OCT at three different depths (150, 300 and 500
      MUm), was performed. Vessels were classified according to morphology (dots,
      blobs, coiled, line, curved, serpiginous), distribution (regular, irregular) and
      the presence/type of branches. The data were correlated with Breslow thickness.
      RESULTS: A total of 127 melanomas were evaluated. Dotted vessels were recorded at
      all depths, and their irregular distribution was associated with lesions thicker
      than 1.0 mm (from 75% to 91%), compared with thin ones (42%) at 150 MUm (P =
      0.031), and from 33% to 57% vs 18% at 300 MUm (P = 0.021). Serpiginous and
      branching vessels with bulges were predominantly seen in melanomas thicker than 2
      mm at 150 MUm (from 14% to 27%, P < 0.001) and 300 MUm of depth (from 36% to 54%,
      P < 0.001). LIMITATIONS: Background noise hampered vessel detection at 500 MUm.
      No correlation with dermoscopy/histology. CONCLUSION: Vascular pattern evaluation
      at 150 and 300 MUm provided data on tumor microvascular asset and its pattern of
      progression in accordance with Breslow thickness. Since vascular progression is
      theoretically linked with tumor aggressiveness, the study of vascular pattern
      related with melanoma metastatization capability is warranted.

PMID- 30218635
TI  - Interspecific and intraspecific transference of metabolism-based mesotrione
      resistance in dioecious weedy Amaranthus.
AB  - Pollen-mediated gene flow (PMGF) might play an important role in dispersing
      herbicide resistance alleles in dioecious weedy Amaranthus species. Field
      experiments in a concentric donor-receptor design were conducted to quantify two
      sets of PMGF studies, an interspecific (Amaranthus tuberculatus * Amaranthus
      palmeri) and an intraspecific (A. tuberculatus * A. tuberculatus). In both
      studies, PMGF was evaluated using a resistant A. tuberculatus phenotype with
      enhanced mesotrione detoxification via P450 enzymes as a source of resistance
      alleles. For interspecific hybridization, more than 104 000 putative hybrid
      seedlings were screened with three markers, one phenotypic and two molecular. The
      two molecular markers used, including 2-bp polymorphisms in the internal
      transcribed spacer region, distinguished A. palmeri, A. tuberculatus and their
      hybrids. Results showed that 0.1% hybridization between A. tuberculatus * A.
      palmeri occurred under field research conditions. For intraspecific
      hybridization, 22 582 seedlings were screened to assess the frequency of gene
      flow. The frequency of gene flow (FGF ) varied with distance, direction and year
      of the study. The farthest distance for 90% reduction of FGF was at 69 m in 2015
      however, after averaging across directions it was 13.1 and 26.1 m in 2014 and
      2015, respectively. This study highlights the transfer of metabolism-based
      mesotrione resistance from A. tuberculatus to A. palmeri under field research
      conditions. The results presented here might aid in the rapid detection of A.
      palmeri among other Amaranthus species and show that PMFG could be expediting the
      increase of herbicide resistance in A. palmeri and A. tuberculatus across US crop
      production areas.

PMID- 30218636
TI  - A lentiviral vector-based insertional mutagenesis screen identifies mechanisms of
      resistance to MAPK inhibitors in melanoma.

PMID- 30218637
TI  - Incidence of surgical site infection after craniotomy: comparison between three
      months and twelve months of epidemiological surveillance.
AB  - OBJECTIVE: To determine the incidence of surgical site infection in patients
      undergoing craniotomy and to compare 12-month and 3-month post-discharge
      surveillance periods in terms of their impact on the incidence of surgical site
      infection in those patients. METHODS: This was a retrospective cohort study
      involving 173 adult patients submitted to "clean" craniotomy, with or without
      implants, during the six-month period, at a university hospital in the city of
      Sao Paulo, Brazil. All the patients were evaluated in the pre-, trans- and
      postoperative periods and were followed for 12 months to analyze the development
      of surgical site infections. RESULTS: Of the 173 patients undergoing craniotomy
      during the study period, 20 developed an surgical site infection during the
      first, and 12 months after discharge, the overall incidence of surgical site
      infection therefore being 11.56%, compared with a 1-month incidence of 8.67% and
      a 3-month incidence of 10.98%. Among the 106 patients who received implants, the
      1-, 3-, and 12-month incidence of surgical site infection was 7.54% (n = 8),
      8.49% (n = 9), and 9.43% (n = 10), respectively. Among the 67 patients who did
      not receive implants, the 1-, 3-, and 12-month incidence of surgical site
      infection was 10.44% (n = 7), 14.92% (n = 10), and 14.92% (n = 10), respectively.
      CONCLUSION: The incidence of surgical site infection after craniotomy is high.
      Reducing the duration of the post-discharge surveillance period from 12 months to
      3 months did not cause significant losses in the numbers of surgical site
      infection identified or a substantial decrease in their incidence.

PMID- 30218638
TI  - Predicting lysine lipoylation sites using bi-profile bayes feature extraction and
      fuzzy support vector machine algorithm.
AB  - Lipoylation is a highly conserved post-translational modification which has been
      found to be involved in many biological processes and closely associated with
      various metabolic diseases. The accurate identification of lipoylation sites is
      necessary to elucidate the underlying molecular mechanisms of lipoylation. As the
      traditional experimental methods are time consuming and expensive, it is desired
      to develop computational methods to predict lipoylation sites. In this study, a
      novel predictor named LipoPred is proposed to predict lysine lipoylation sites.
      On the one hand, an effective feature extraction method, bi-profile bayes
      encoding, is employed to encode lipoylation sites. On the other hand, a fuzzy
      support vector machine algorithm is proposed to solve the class imbalance and
      noise problem in the prediction of lipoylation sites. As illustrated by 10-fold
      cross-validation, LipoPred achieves an excellent performance with a Matthew's
      correlation coefficient of 0.9930. Therefore, LipoPred can be a useful
      bioinformatics tool for the prediction of lipoylation sites. Feature analysis
      shows that some residues around lipoylation sites may play an important role in
      the prediction. The results of analysis and prediction could offer useful
      information for elucidating the molecular mechanisms of lipoylation. A user
      friendly web-server for LipoPred is established at 123.206.31.171/LipoPred/.

PMID- 30218639
TI  - Purification of equine IgG3 by lectin affinity and an interaction analysis via
      microscale thermophoresis.
AB  - The availability of purified antibodies is a prerequisite for many applications
      and the appropriate choice(s) for antibody-purification is crucial. Numerous
      methods have been developed for the purification of antibodies from different
      sources with affinity chromatography-based methods being the most extensively
      utilized. These methods are based on high specificity, easy reversibility and
      biological interactions between two molecules (e.g., between receptor and ligand
      or antibody and antigen). However, no simple techniques have yet been described
      to characterize and purify subclasses of immunoglobulins (Ig) from some animals
      of biotechnology importance such as equines, which are frequently used to produce
      biotherapeutic antibodies. The sera of these animals present a large number of Ig
      classes that have a greater complexity than other animals. The implementation of
      an effective protocol to purify the desired antibody class/subclasses requires
      meticulous planning to achieve yields at a high purity. The IgG3 subclass of
      equine-Ig has recently been used as antigen in a new diagnostic test for allergic
      responses to horse sera-based therapies. Here, we defined a simple method using
      Jacalin lectin immobilized on Sepharose beads to prepare highly pure equine IgG3
      antibodies with a determination of the affinity constants for Jacalin lectin and
      horse IgG3.

PMID- 30218640
TI  - Trajectories of Self-Efficacy and Depressed Mood and Their Relationship in the
      First 12 Months Following Spinal Cord Injury.
AB  - OBJECTIVES: To establish self-efficacy and depressive mood trajectories in adults
      with spinal cord injury (SCI), determine their interrelationship over time, and
      determine the influence that appraisals and comorbid physical conditions have on
      the development of self-efficacy. DESIGN: A prospective cohort design. SETTING:
      Inpatient rehabilitation and community settings. PARTICIPANTS: Adults (N=88)
      admitted consecutively into 3 SCI units (mean age, 42.6 years, 70.4% male, 61%
      paraplegia). INTERVENTIONS: Multidisciplinary inpatient SCI rehabilitation. MAIN
      OUTCOME MEASURES: The Moorong Self-Efficacy Scale and Hospital Anxiety and
      Depression Scale were used to model self-efficacy and depressive mood
      trajectories. Appraisals were assessed using the Appraisals of Disability Scale
      and frequency/type of secondary conditions using the Secondary Conditions Scale.
      Growth mixture modeling was used to determine trajectories. Dual trajectory
      probability analysis was used to determine concurrent changes in self-efficacy
      and depressive mood. Linear mixed modeling incorporating repeated measures
      determined the contribution of appraisals and physical complications to self
      efficacy trajectories. RESULTS: Modeling identified 4 trajectories of self
      efficacy and depressive mood. The majority (around 60%) of the sample was
      estimated to have moderate to high self-efficacy and low levels of depressive
      mood. Dual trajectory analysis revealed that robust self-efficacy was strongly
      connected to low depressive mood over time, while low self-efficacy was strongly
      linked to clinically elevated depressive mood. Low self-efficacy was related to
      higher severity of secondary conditions and negative appraisals. CONCLUSIONS:
      Findings highlight the importance of self-efficacy not only as a strategic
      clinical measure for assessing adjustment following SCI but also in relation to
      the implications it raises for improving SCI rehabilitation.

PMID- 30218641
TI  - Ability of Patient-Reported Outcomes to Characterize Patient Acceptable Symptom
      State (PASS) After Attending a Primary Care Physical Therapist and Medical Doctor
      Collaborative Service: A Cross-Sectional Study.
AB  - OBJECTIVES: To determine if the Patient-Reported Outcome Measurement Information
      System (PROMIS) physical function, pain interference, self-efficacy, and global
      rating of normal function (GRNF) scales are able to accurately characterize a
      patient's acceptable symptom state (PASS). DESIGN: A cross-sectional analysis,
      using receiver operator curves and chi-square analysis to explore criteria to
      determine thresholds (80% and 95% sensitivity/specificity) for PASS that are
      applicable to PROMIS and GRNF scales. SETTING: Phone survey after primary care.
      PARTICIPANTS: Patients (N=94) attending primary care for musculoskeletal
      problems. INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Accuracy and
      proportion of patients classified as PASS Yes or No. RESULTS: Receiver operator
      curve analysis showed significant area under the curve (AUC) values for each
      PROMIS scale (AUC>.72) and the GRNF rating (AUC=.74). Identified PROMIS
      thresholds suggested PASS was achieved when scores were at or slightly worse than
      the US population average. A score of >=7 and <=4 characterized patients that
      were PASS Yes and No, respectively, on the GRNF rating. A moderate (80%)
      specificity/sensitivity criteria yielded 72.3%-73.5% accuracy for a majority of
      participants (>69.9%). CONCLUSION: This analysis suggests the PROMIS and GRNF
      scales are able to characterize PASS status with moderate accuracy (~70%) for a
      large portion of patients (~70%). New to this study is the association of self
      efficacy with PASS status. PROMIS scales at or slightly worse than the US
      population average characterized PASS status.

PMID- 30218642
TI  - Distinct requirements of E2f4 versus E2f5 activity for multiciliated cell
      development in the zebrafish embryo.
AB  - Multiciliated cells (MCCs) differentiate arrays of motile cilia that beat to
      drive fluid flow over epithelia. Recent studies have established two Geminin
      family coiled-coil containing nuclear regulatory proteins, Gmnc and Multicilin
      (Mci), in the specification and differentiation of the MCCs. Both Gmnc and Mci
      are devoid of a DNA binding domain: they regulate transcription by associating
      with E2f family transcription factors, notably E2f4 and E2f5. Here, we have
      studied the relative contribution of these two E2f factors in MCC development
      using the zebrafish embryo, which differentiates MCCs within kidney tubules and
      the nose. We found that while E2f4 is fully dispensable, E2f5 is essential for
      MCCs to form in the kidney tubules. Moreover, using a variety of double mutant
      combinations we show that E2f5 has a more prominent role in MCC development in
      the zebrafish than E2f4. This contrasts with current evidence from the mouse,
      where E2f4 seems to be more important. Thus, distinct combinatorial activities of
      the E2f4 and E2f5 proteins regulate the specification and differentiation of MCCs
      in zebrafish and mice.

PMID- 30218644
TI  - Faster, cheaper, defined and efficient vitrification for immature porcine oocytes
      through modification of exposure time, macromolecule source and temperature.
AB  - Vitrification reduces the developmental competence of porcine immature oocytes.
      We investigated the effects of modifying various factors on the viability and
      development of oocytes after vitrification. These factors included: 1) exposure
      to the vitrification solution, 2) macromolecule addition (bovine serum albumin
      (BSA) or polyvinyl pyrrolidone (PVP)), 3) treatment with cytochalasin B, 4)
      equilibration temperature, and 5) vitrification method (microdrop or Cryotop).
      Oocytes were equilibrated and vitrified using medium containing ethylene glycol
      and propylene glycol. After warming, oocytes were subjected to in vitro
      maturation, stimulated parthenogenetically, and cultured in vitro. Survival rate,
      nuclear maturation, cleavage, development to the blastocyst stage and their
      quality were compared between the vitrified groups and the non-vitrified control
      group. It was found that 1) exposure to the vitrification solution for longer
      than 30 s was detrimental to embryo development; 2) replacement of BSA with PVP
      improved embryo development; 3) cytochalasin B treatment reduced the survival
      rates, but did not affect the blastocyst development rates, 4) equilibration at
      room temperature (25  degrees C) was the most beneficial, and 5) the microdrop
      method improved survival rates. With these adjustments, we were able to establish
      a simplified and defined cryopreservation system for porcine immature oocytes
      with improved efficacy.

PMID- 30218645
TI  - MiR-155 aggravated septic liver injury by oxidative stress-mediated ER stress and
      mitochondrial dysfunction via targeting Nrf-2.
AB  - OBJECTIVE: Liver is uniquely vulnerable during sepsis. MicroRNA-155 (miR-155) is
      confirmed to play crucial roles in septic liver injury. The present study aims to
      investigate the mechanisms of miR-155 in septic liver injury. METHODS: The sepsis
      model was established by intraperitoneal injection of lipopolysaccharide (LPS) in
      mice. Mice were divided into four groups: Vehicle, miR-155 antagomir, LPS, LPS+
      miR-155 antagomir. The survival rate and body weight were monitored. Liver injury
      was assessed by H&E staining. The levels of serum ALT and inflammatory cytokines
      were determined by ELISA kits. Oxidative stress was detected by MDA and SOD
      detection kits. The miR-155, Nrf-2, and markers related to oxidative stress,
      endoplasmic reticulum (ER) stress, mitochondrial injury and apoptosis were
      detected by western blotting and qPCR. Apoptosis in liver tissues was detected by
      TUNELstaining. RESULTS: MiR-155 antagomir alleviated liver injury as evidenced by
      enhancing survival rate and body weight, inhibiting inflammatory cell
      infiltration, liver cells necrosis and decreasing ALT level. The productions of
      TNF-alpha, IL-6 were suppressed, while anti-inflammatory cytokine IL-10 was
      promoted by miR-155 antagomir. Oxidative stress was inhibited by miR-155
      antagomir via enhancing nuclear factor, erythroid 2-like 2 (Nrf-2) expression. ER
      stress and Cytochrome C (Cyto-C) release were restrained by miR-155 antagomir.
      Sepsis-induced apoptosis was repressed by miR-155 antagomir as manifested by the
      decreased levels of Bax, cleaved caspase-12, 9 and 3, and increased levels of Bcl
      2 and uncleaved PARP. CONCLUSION: MiR-155 antagomir relieved septic liver injury
      through inhibiting oxidative stress-mediated ER stress, mitochondrial dysfunction
      and apoptosis via targeting Nrf-2, suggesting miR-155 as a therapeutic target for
      septic liver injury.

PMID- 30218646
TI  - Clinical and endoscopic predictors for intraprocedural mucosal injury during per
      oral endoscopic myotomy.
AB  - BACKGROUND AND AIMS: Mucosal injury (MI) is one of the most common perioperative
      adverse events of per-oral endoscopic myotomy (POEM). Severe undertreated MI may
      lead to contamination of the tunnel and even mediastinitis. This study explored
      the characteristics, predictors, and management approaches of intraoperative MI.
      METHODS: A retrospective review of the prospectively collected database at a
      large tertiary referral endoscopy unit was conducted for all patients undergoing
      POEM between August 2010 and March 2016. MI was graded according to the
      difficulty of repair (I, easy to repair; II, difficult to repair). The primary
      outcomes were the incidence and predictors of intraoperative MI. Secondary
      outcomes were MI details and the corresponding treatment. RESULTS: POEM was
      successfully performed in 1912 patients. A total of 338 patients experienced 387
      MIs, for an overall frequency of 17.7% (338/1912). Type II MI was rare, with a
      frequency of 1.7% (39/1912). Major adverse events were more common in patients
      with MI than in those without MI (6.2% vs 2.5%, P < .001). On multivariable
      analysis, MI was independently associated with previous Heller myotomy (odds
      ratio [OR], 2.094; P = .026), previous POEM (OR, 2.441; P = .033), submucosal
      fibrosis (OR, 4.530; P < .001), mucosal edema (OR, 1.834; P = .001), and tunnel
      length >=13 cm (OR, 2.699; P < .001). Previous POEM (OR, 5.005; P = .030) and
      submucosal fibrosis (OR, 12.074; P < .001) were significant predictors of type II
      MI. POEM experience >1 year was a protective factor for MI (OR, .614; P = .042)
      and type II MI (OR, .297; P = .042). CONCLUSIONS: MI during POEM is common, but
      type II injury is rare. Previous POEM and submucosal fibrosis were significant
      predictors of type II mucosal injury. POEM experience after the learning curve
      reduces the risk of MI.

PMID- 30218647
TI  - Lizards perceived abiotic and biotic stressors independently when competing for
      shade in terrestrial mesocosms.
AB  - Hormones such as glucocorticoids and androgens enable animals to respond
      adaptively to environmental stressors. For this reason, circulating
      glucocorticoids became a popular biomarker for estimating the quality of an
      environment, and circulating androgens are frequently used to indicate social
      dominance. Here, we show that access to thermal resources influence the hormones
      and behavior of male lizards (Sceloporus jarrovi). We exposed isolated and paired
      males to different thermal landscapes, ranging from one large patch of shade to
      sixteen smaller patches. Both the presence of a competitor and the patchiness of
      the thermal environment influenced hormone concentrations and movement patterns.
      When shade was concentrated in space, paired lizards competed more aggressively
      and circulated more corticosterone. Even without competitors, lizards circulated
      more corticosterone in landscapes with fewer patches of shade. Conversely, shifts
      in circulating testosterone depended only on the relative body size of a lizard;
      when paired, large males and small males circulated more and less testosterone,
      respectively. Furthermore, isolated males moved the farthest and covered the most
      area when shade was concentrated in a single patch, but paired males did the
      opposite. Because the total area of shade in each landscape was the same, these
      hormonal and behavioral responses of lizards reflect the ability to access shade.
      Thus, circulating glucocorticoids should reflect the thermal quality of an
      environment when researchers have controlled for other factors. Moreover, a
      theory of stress during thermoregulation would help ecologists anticipate
      physiological and behavioral responses to changing climates.

PMID- 30218649
TI  - Optimizing Sleep in the Military: Challenges and Opportunities.
AB  - Historically, scientific knowledge gaps-including a lack of information regarding
      the minimum amount of sleep needed to sustain nominally adequate, militarily
      relevant performance, and nescience of the potential impact of chronic sleep
      restriction on health and psychological well-being-have hindered decision-making
      vis-a-vis sleep/alertness management in operational environments. However,
      against a backdrop of increasing awareness of the importance of sleep for
      sustaining both performance and health, military researchers are currently doing
      the following: (1) developing a comprehensive, individualized sleep/alertness
      management system to optimize the general effectiveness of military personnel
      (ie, without regard to the potential relationship between sleep and specific
      aspects of military performance, thus sidestepping what has historically been an
      impediment to development of such a system); and (2) investigating the
      prevalence, potentially unique etiology (eg, resulting from the interaction of
      long-term exposure to combat-related stressors and sleep restriction), and
      treatment of sleep disorders and comorbidities in the military population.

PMID- 30218648
TI  - Stochastic modeling of tumor progression and immune evasion.
AB  - It is now well-established that the host's adaptive immune system plays an
      important role in identifying and eliminating cancer cells in much the same way
      that intracellular pathogens are cleared during an adaptive immune response to
      infection. From a therapeutic standpoint, the adaptive immune system is unique in
      that it can co-evolve alongside a developing tumor. Tumor acquisition of immune
      evasive phenotypes, such as class-I MHC down-regulation, remains a major
      limitation of successful T-cell immunotherapy. Here, we consider a population
      dynamical model coupling tumor and adaptive immune compartments in order to study
      the dynamics and survival of an evolving threat when faced with adaptive immune
      pressure. We demonstrate that predicted optimal growth strategies depend on
      whether or not the threat may acquire an immune-evasive phenotype as well as the
      mode of immune detection. We parameterize adaptive immune functioning by T-cell
      turnover and repertoire diversity and predict that decreases in the latter
      quantity which occur in advanced age may substantially affect the ability to
      recognize, and therefore control, an immune evasive threat like cancer. This
      framework recapitulates general features of age-dependent AML incidence, thereby
      providing a probable association between cancer frequency and adaptive immune
      functioning. Lastly, we quantify therapeutic efficacy of adjuvant
      immunotherapeutic strategies, and predict their benefits and limitations with
      regard to handling immune evasion. Our model generates survival behavior
      consistent with known growth-dependent characteristics, and serves as a first
      attempt at modeling stochastic cancer evolution alongside an adaptive immune
      compartment.

PMID- 30218650
TI  - Insights into ZIKV-Mediated Innate Immune Responses in Human Dermal Fibroblasts
      and Epidermal Keratinocytes.
AB  - Zika virus (ZIKV) has emerged as a global pathogen causing significant public
      health concern. ZIKV infections in humans principally occur via mosquito bites.
      Thus, host skin cells are permissive to ZIKV infection and are the first line of
      defense against the virus. Here, we examined the role and mechanisms of antiviral
      skin immunity against ZIKV infection. ZIKV infection (African lineage MR766) in
      human dermal fibroblasts, human epidermal keratinocytes, and HaCaT keratinocytes
      resulted in distinct expression changes in RIG-I-like receptors, such as RIG-I
      and MDA5. Inhibition of RIG-I using small interfering RNA resulted in increased
      viral gene expression and reduced induction of IFNs and IFN-stimulated genes.
      Furthermore, ZIKV NS1 directly interacted with RIG-I or MDA5 and down-regulated
      RIG-I-like receptor-mediated antiviral signaling pathways. Asian lineage ZIKV
      (PRVABC59) infection also showed a distinct pattern of antiviral immunity in
      human skin cells, compared with other ZIKV strains. Additionally, ZIKV infections
      in human neural progenitor cells induced the robust activation of RIG-I-like
      receptor-mediated signaling, followed by highly enhanced IFN-stimulated gene
      expression. Our findings provide important insights into ZIKV tropism and
      subsequent antiviral signaling pathways that regulate ZIKV replication in human
      dermal fibroblasts and human epidermal keratinocytes.

PMID- 30218651
TI  - Optogenetic approaches to vision restoration.
AB  - Inherited retinal disease (IRD) affects about 1 in 3000 to 1 in 5000 individuals
      and is now believed to be the most common cause of blindness registration in
      developed countries. Until recently, the management of such conditions had been
      exclusively supportive. However, advances in molecular biology and medical
      engineering have now seen the rise of a variety of approaches to restore vision
      in patients with IRDs. Optogenetic approaches are primarily aimed at rendering
      secondary and tertiary neurons of the retina light-sensitive in order to replace
      degenerate or dysfunctional photoreceptors. Such approaches are attractive
      because they provide a "causative gene-independent" strategy, which may prove
      suitable for a variety of patients with IRD. We discuss theoretical and practical
      considerations in the selection of optogenetic molecules, vectors, surgical
      approaches and review previous trials of optogenetics for vision restoration.
      Optogenetic approaches to vision restoration have yielded promising results in
      pre-clinical trials and a phase I/II clinical trial is currently underway
      (ClinicalTrials.gov NCT02556736). Despite the significant inroads made in recent
      years, the ideal optogenetic molecule, vector and surgical approach have yet to
      be established.

PMID- 30218652
TI  - Immunological responsiveness of intestinal tissue explants and mucosal
      mononuclear cells to ex vivo stimulation.
AB  - BACKGROUND: There are limited data on the immunological responsiveness of healthy
      intestinal tissue when it is cultured and stimulated ex vivo. Such an ex vivo
      model has the potential to be a valuable tool in understanding disease
      pathogenesis and as a preclinical tool for the assessment of candidate
      therapeutic agents used to treat inflammatory bowel disease (IBD). AIM: We
      undertook a comprehensive study to evaluate ex vivo immunological responses of
      intestinal tissue and isolated mucosal mononuclear cells (MMC) to a broad range
      of stimuli. METHODS: Colorectal biopsies (explants) were obtained from healthy
      participants by flexible sigmoidoscopy and were placed either directly into
      culture or digested to isolate MMC prior to placement in culture. Explants or MMC
      were treated with polyinosinic:polycytidylic acid (Poly IC), phytohemagglutinin
      (PHA), lipopolysacccharides from E Coli (LPS), anti-CD3/CD28 antibodies, or IL
      1beta/TNF-alpha for 24 h. Supernatants were assayed for 40 inflammatory
      biomarkers using multiplexed enzyme-linked immunosorbent assay (ELISA). The
      isolated MMCs were further characterized using twelve color flow cytometry.
      RESULTS: Explants have greater weight adjusted constitutive expression of
      inflammatory biomarkers than MMCs. Biomarker responses varied as a function of
      immunogen and use of intact tissue or isolated cells. PHA applied to intact
      explants was the most effective agent in inducing biomarker changes. Stimulation
      induced activated and memory cellular phenotypes in both explants and MMCs.
      CONCLUSIONS: The breadth and magnitude of responses from intact and enzymatically
      digested intestinal tissue explants stimulated with exogenous immunogens are
      complex and vary by tissue form and treatment. Overall, PHA stimulation of intact
      explants produced the most robust responses in normal human colorectal tissue.
      This system could potentially serve as a preliminary model of the disease state,
      suitable for small scale screening of new therapeutic agents prior to using IBD
      patient derived tissue.

PMID- 30218653
TI  - Functional Mandibular Reconstruction With Double-Barrel Fibular Flap and Primary
      Osseointegrated Dental Implants Improve Facial Esthetic Outcome.
AB  - PURPOSE: Osseointegrated dental implants in fibula free flaps can be used to
      reconstruct segmental mandibular defects resulting from head and neck resections.
      The double-barrel fibula flap (DBFF) has been applied as a modified method to
      overcome insufficient fibular width. This article describes the use of the DBFF
      with simultaneous dental implant placement as a superior method for esthetic
      mandibular reconstruction. MATERIALS AND METHODS: From 2012 to 2015, 26 patients
      underwent mandibular reconstruction with a free fibula flap and immediate dental
      implant placement after segmental mandibulectomies. Twelve patients received the
      DBFF and the other 14 patients received the conventional single-barrel fibula
      flap (SBFF). Palatal mucosal grafting was performed when necessary. Functional
      and esthetic outcomes were evaluated after 31 to 45 months of follow-up. RESULTS:
      All microvascular fibula transplantations were successful. All patients completed
      prosthodontic rehabilitation. The mean follow-up of patients after reconstruction
      was 36.3 months (range, 31 to 45 months). The facial esthetic score was
      significantly higher in patients treated with the DBFF than with the SBFF after
      24 and 30 months (P < .05). There was no significant difference in marginal bone
      resorption between the DBFF and SBFF groups (P > .05). CONCLUSIONS: This 1-stage
      surgical method is safe and reliable. Use of the DBFF markedly decreased the
      height discrepancy between the native and new mandible and achieved a better
      lower face esthetic outcome than the SBFF. Osseointegrated dental implantation
      was adequate to achieve satisfactory dental rehabilitation in the DBFF group.

PMID- 30218654
TI  - Elective Neck Dissection Versus Observation in Squamous Cell Carcinoma of Oral
      Cavity With Clinically N0 Neck: A Systematic Review and Meta-Analysis of
      Prospective Studies.
AB  - PURPOSE: To assess the possible benefits of elective neck dissection (END) in
      patients with squamous cell carcinoma (SCC) of the oral cavity and clinically N0
      neck. MATERIALS AND METHODS: Medline, Embase, the China National Knowledge
      Infrastructure, and the Wan Fang Database were systematically searched. A meta
      analysis was performed to evaluate the possible benefits of END to such patients.
      RESULTS: Six prospective studies involving 865 patients fulfilled the inclusion
      criteria. Meta-analysis of all included studies showed that END substantially
      lowered the risk of regional recurrences (risk ratio [RR] = 0.27; 95% confidence
      interval [CI], 0.21-0.36) in the fixed-effect model compared with observation
      only. Three of the 6 included studies showed that the specific death rate related
      to regional recurrences was lower in the END group than in the observation group
      in the fixed-effect model (RR = 0.35; 95% CI, 0.19-0.65). The mean metastasis
      rate of occult cervical lymph node was 30.27% (standard deviation, 9.42%). When
      the fixed-effect model was applied, 4 of the 6 included studies showed less
      recurrence in the END group compared with the observation group (RR = 0.53; 95%
      CI, 0.44-0.64). CONCLUSIONS: END substantially decreases recurrences and deaths
      related to regional recurrences in early-stage SCC of the oral cavity with
      clinically N0 neck, especially SCC of the oral tongue and floor of the mouth,
      which is necessary for such patients.

PMID- 30218656
TI  - Metabolomics analysis of oral mucosa reveals profile perturbation in reticular
      oral lichen planus.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory mucosal disorder
      and potentially oral premalignant lesion affecting the stratified squamous
      epithelia. In OLP, reticular type is the most common clinical form of the
      disease. However, little is known about it. Metabolomics analysis may help to
      investigate the disease pathogenesis and to improve clinical treatment. METHODS:
      Liquid chromatography (LC)-mass spectrometry (MS) system, XCMS software, SIMCA
      software, and OSI / SMMS software were integrated to identify differentially
      expressed metabolites for the pathways and pathology analysis. RESULTS: Totally,
      21 modulated metabolites were identified, whose dysregulations affected 30
      metabolic pathways. Through an impact-value screen (impact-value>0.1), 8 pathways
      were selected as the significantly dysregulated pathways. Pathological network
      showed that these metabolites participated in 5 pathological processes, that is,
      inflammatory lesion, DNA damage and repair disorder, apoptosis process, oxidative
      stress injury, and abnormal energy expenditure. CONCLUSION: The study revealed
      the metabolic perturbation of oral mucosa in reticular OLP, which may provide an
      important reference for the understanding of the pathogenesis of the disease and
      the discovery of therapeutic targets.

PMID- 30218655
TI  - Development of Medication-Related Osteonecrosis of the Jaw After Extraction of
      Teeth With Experimental Periapical Disease.
AB  - PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but severe
      side effect of antiresorptive medications. Most animal models use tooth
      extraction as an instigating local factor to induce MRONJ, with varied results.
      However, these teeth are healthy and absent of dental disease, a rare finding
      that does not reflect clinical practices. The authors hypothesized that
      extraction of teeth with periapical inflammation would lead to MRONJ in rats
      treated with high-dose bisphosphonates. MATERIALS AND METHODS: Rats were
      pretreated with zoledronic acid (ZA) for 1 week. Pulp exposure (PE) was
      established by exposing the pulpal chamber of the first and second molars.
      Experimental periapical disease (EPD) was induced by PE and bacterial inoculation
      into pulp chambers of the first and second mandibular molars. The mandibular
      molars were extracted 4 weeks after PE or EPD, and animals were euthanized 4
      weeks after tooth extraction. Extraction sockets were assessed clinically,
      radiographically, and histologically. RESULTS: Clinically, radiographically, and
      histologically, socket healing was observed in all vehicle-treated animals and in
      ZA-treated animals after extraction of healthy teeth or teeth with PE. In
      contrast, bone exposure, lack of socket healing, and osteonecrosis were present
      in most ZA-treated animals after extraction of teeth with EPD. Bacterial presence
      was noted in areas of osteonecrotic alveolar bone. CONCLUSION: These data support
      a synergistic contribution of severe dental disease and tooth extraction to MRONJ
      pathogenesis. Importantly, this model is amenable to manipulation of methodologic
      conditions for the dissection of parameters involved in MRONJ pathogenesis.

PMID- 30218657
TI  - An automated method for measuring lipoprotein lipase and hepatic triglyceride
      lipase activities in post-heparin plasma.
AB  - BACKGROUND: Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) play
      a central role in triglyceride-rich lipoprotein metabolism by catalyzing the
      hydrolysis of triglycerides. Quantification of LPL and HTGL activity is useful
      for diagnosing lipid disorders, but there has been no automated method for
      measuring these lipase activities. METHODS: The automated kinetic colorimetric
      method was used for assaying LPL and HTGL activity in the post-heparin plasma
      using the natural long-chain fatty acid 2-diglyceride as a substrate. LPL
      activity was determined with apoCII and HTGL activity was determined without
      apoCII with 2 channel of auto-analyzer. RESULTS: The calibration curve for
      dilution tests of the LPL and HTGL activity assay ranged from 0.0 to 500 U/L.
      Within-run CV was obtained within a range of 5%. No interference was observed in
      the testing of specimens containing potentially interfering substances. The
      measurement range of LPL activity in the post-heparin plasma was 30-153 U/L,
      while HTGL activity was 135-431 U/L in normal controls. CONCLUSIONS: The L PL and
      HTGL activity assays are applicable to quantitating the LPL and HTGL activity in
      the post-heparin plasma. This assay is more convenient and faster than
      radiochemical assay and highly suitable for the detection of lipid disorders.

PMID- 30218658
TI  - The correlation between Runx3 and bronchial asthma.
AB  - Runx3, a member of the Runt-related transcription factor family, has attracted
      extensive attention due to its important role in the development of immune
      systems, especially in the differentiation of T cells. Accumulated evidence
      indicated that altered expression of Runx3 regulates a variety of target genes in
      different tissues/cells. Studies in animal models suggested that Runx3 may
      regulate the development of T cell lineage including those of innate lymphoid
      cells, Treg cells and dendritic cells, which may contribute to the development of
      hypersensitivity and asthma. Specifically, Runx3 modulates Th1/Th2 balance and
      hence, the production of interleukins, which induce inflammatory responses.
      Understanding the roles and mechanisms of Runx3 in the regulation of immune
      function provides a basis for the design of novel preventive and treatment models
      for bronchial asthma. This article reviews published data from cell lines, animal
      models, and patients, concerning the relationship between Runx3 expression
      alteration and asthma. Epigenetic regulation of Runx3 by DNA hypermethylation and
      microRNA, and the implication of these pathways in asthma are also discussed.

PMID- 30218659
TI  - Red blood cell distribution width predicts long-term outcomes in sepsis patients
      admitted to the intensive care unit.
AB  - BACKGROUND: Although some underpowered studies have proven that increased red
      blood cell distribution width (RDW) may be associated with short-term prognosis
      of sepsis, the long-term prognostic value of RDW remains largely unknown.
      METHODS: This retrospective observational study was based on the Medical
      Information Mart for Intensive Care III (MIMIC III), a large critical care
      database. Baseline RDW and conventional disease severity scores were extracted
      along with data on 4-year mortality, of adult patients with severe sepsis upon
      first admission to the intensive care unit (ICU). The prognostic value of RDW was
      analyzed with Kapan-Meier cure, Cox model, receiver operating characteristic
      (ROC) curve analysis, net reclassification index (NRI) and integrated
      discriminatory index (IDI). RESULTS: A total of 4264 subjects were included. The
      area under ROC curve of RDW for predicting 4-year mortality was 0.64 (95% CI:
      0.63-0.66). In multivariable Cox model, increased RDW was independently
      associated with all-cause mortality, irrespective of anemia. With conventional
      severity scores as reference, RDW had continuous NRI comprised between 0.18 and
      0.20, and IDI comprised between 0.30 and 0.40. CONCLUSION: RDW values
      significantly predicts long-term all-cause mortality in critically ill patients
      with severe sepsis beyond conventional severity scores.

PMID- 30218660
TI  - Lipoprotein lipase transporter GPIHBP1 and triglyceride-rich lipoprotein
      metabolism.
AB  - Increased plasma triglyceride serves as an independent risk factor for
      cardiovascular disease (CVD). Lipoprotein lipase (LPL), which hydrolyzes
      circulating triglyceride, plays a crucial role in normal lipid metabolism and
      energy balance. Hypertriglyceridemia is possibly caused by gene mutations
      resulting in LPL dysfunction. There are many factors that both positively and
      negatively interact with LPL thereby impacting TG lipolysis.
      Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1
      (GPIHBP1), a newly identified factor, appears essential for transporting LPL to
      the luminal side of the blood vessel and offering a platform for TG hydrolysis.
      Numerous lines of evidence indicate that GPIHBP1 exerts distinct functions and
      plays diverse roles in human triglyceride-rich lipoprotein (TRL) metabolism. In
      this review, we discuss the GPIHBP1 gene, protein, its expression and function
      and subsequently focus on its regulation and provide critical evidence supporting
      its role in TRL metabolism. Underlying mechanisms of action are highlighted,
      additional studies discussed and potential therapeutic targets reviewed.

PMID- 30218661
TI  - Immunohistochemical localization of megalin and cubilin in the human inner ear.
AB  - Megalin and cubilin are endocytic receptors expressed in many absorptive
      polarized epithelia. These receptors have been implicated in the transport of
      gentamicin in the inner ear as possible contributors to ototoxic damage. Megalin
      and cubilin have been characterized in detail in the mouse and rat inner ear, but
      not in the human inner ear. In this study, megalin and cubilin were localized by
      immunohistochemistry using affinity-purified antibodies in formalin fixed frozen
      cryostat and celloidin embedded sections of the human inner ear. In the cochlea
      megalin and cubilin were localized in marginal cells of the stria vascularis,
      epithelial cells of the spiral prominence and the Reissner's membrane. In the
      macula utricle and cristae ampullaris, megalin and cubilin were localized in
      transitional and dark cells, but not in vestibular hair cells and supporting
      cells. In the endolymphatic duct megalin and cubilin were localized in the
      epithelial cells. The localization of megalin and cubilin in the human inner ear
      is consistent with previous reports in the inner ear of animal models and suggest
      that these receptors may play an important role in the inner ear endocytic
      transport, and maybe potential targets for prevention of ototoxic damage or the
      delivery of medications.

PMID- 30218662
TI  - Graft Replacement Kommerell's Diverticulum and In-Situ Aberrant Subclavian Artery
      Reconstruction.
AB  - BACKGROUND: The study aimed to evaluate the early and long-term outcomes
      following graft replacement of Kommerell's diverticulum and in-situ
      reconstruction of aberrant subclavian arteries in adults. METHODS: Seventeen
      patients, of whom 6 patients were symptomatic and 11 had right aortic arch,
      underwent open repair of Kommerell's diverticulum from October 1999 to September
      2017. Two of these patients underwent open surgery for a ruptured aneurysm.
      Indications for surgery were dilatation of Kommerell's aneurysm (n = 9), presence
      of a non-dissecting aneurysm with Kommerell's diverticulum (n = 6), acute type A
      aortic dissection (n = 1), and complicated acute type B aortic dissection (n =
      1). Ten patients underwent replacement total arch and descending aorta
      replacement via a thoracotomy. Five patients underwent arch replacement and in
      situ reconstruction via a median sternotomy. All patients except 1 also underwent
      in-situ reconstruction of their aberrant subclavian artery. RESULTS: Hospital
      mortality occurred in 1 patient (5.9%), who underwent total arch replacement for
      a ruptured aneurysm. Permanent neurological deficit did not occur in any patient,
      while transient neurological deficit occurred in 2 patients (11.8%). Five-year
      and 10-year survival were 85.2 +/- 9.8% and 75.8 +/- 12.5%, respectively. There
      was no symptom recurrence or stenosis of the reconstructed subclavian arteries.
      CONCLUSIONS: Early outcomes following graft replacement of Kommerell's
      diverticulum and in-situ aberrant subclavian artery reconstruction were
      acceptable. In terms of long-term outcomes, symptomatic improvement and an
      excellent patency rate among reconstructed aberrant subclavian arteries suggest
      that in-situ surgical repair is an effective treatment option.

PMID- 30218663
TI  - Air Leak Management Program With Digital Drainage Reduces Length of Stay After
      Lobectomy.
AB  - BACKGROUND: Air leaks can impede recovery from lung resection. To help prevent
      and manage air leaks, we developed a comprehensive program that includes using
      precompression of lung staple lines, sealant, fissureless video-assisted
      thoracoscopic (VATS) lobectomy, a digital drainage system, and endobronchial
      valve placement for prolonged air leak. We assessed the effectiveness of this
      program on air leak duration, hospital length of stay (LOS), and chest tube
      duration in our high-risk veteran population. METHODS: Using a prospectively
      maintained database, we retrospectively analyzed data from 226 patients who
      underwent lung resection for cancer by VATS lobectomy in a Veterans Affairs
      center. Patients were divided into two groups. Group A (n = 134; historical
      controls) underwent lobectomy from July 2009 through October 2013; group B (n =
      92; intervention group) underwent lobectomy from November 2013 through July 2016
      and received care per the comprehensive program. RESULTS: The median hospital LOS
      was significantly shorter in group B than in group A patients (5 days versus 6
      days, respectively; p = 0.0001). Group B had a shorter median chest tube duration
      (2 days versus 3 days, p = 0.027). Prolonged air leak (more than 5 days) occurred
      in 5.4% of group B and 9.7% of group A patients (p = 0.24). Prolonged LOS (more
      than 14 days) was less frequent in group B (1.1%) than in group A (8.2%, p =
      0.030). Multivariable analysis showed that predictors of decreased air leak
      duration, chest tube duration, and LOS included undergoing surgery in the later
      period (group B). CONCLUSIONS: Our comprehensive program was associated with
      reduced chest tube days and hospital LOS.

PMID- 30218664
TI  - Preoperative Dye Localization for Thoracoscopic Lung Surgery: Hybrid Versus
      Computed Tomography Room.
AB  - BACKGROUND: Preoperative computed tomography (CT)-guided dye localization is
      essential for the surgical treatment of small lung nodules and is mostly
      performed by radiologists in the CT room. Several studies reported their early
      experiences of preoperative localization in the hybrid operating room. A
      comparison between localization in the CT room and hybrid room has not been
      reported. Therefore, we compared the outcomes of preoperative localization in the
      hybrid and CT rooms. METHODS: This study included patients who underwent
      preoperative CT-guided dye localization for thoracoscopic lung tumor surgery in
      the hybrid operation room (n = 25) and CT room (n = 283) at our institute.
      Propensity matched analysis, incorporating nodule size, number, and depth, and
      operation method, was used to compare the short-term outcomes of these two
      groups. Each patient in the hybrid room group was matched with 2 patients in the
      CT room group. RESULTS: Localization was successfully performed in 23 patients
      (92%) and 50 patients (100%) in the hybrid room and CT room groups, respectively.
      There was no significant difference in demographics between groups. In the hybrid
      room group, the global time was shorter (192.6 versus 244.1 minutes, p = 0.003),
      and the localization time was longer (33.1 versus 22.3 minutes, p < 0.001). All
      lung nodules were successfully resected in both groups, but the hybrid room group
      had a relatively higher morbidity rate. CONCLUSIONS: The hybrid operating room
      may be associated with a shorter global time and similar perioperative and
      postoperative outcomes compared with the CT room. Localization in the hybrid
      operating room seems an effective alternative method for managing small lung
      nodules.

PMID- 30218665
TI  - Tumor Lysis Syndrome after Bilobectomy for Typical Carcinoid Tumor of the Lung.
AB  - Tumor lysis syndrome (TLS) is a life-threatening complication comprised of
      hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia attributed to
      release of intracellular contents. While traditionally associated with leukemia
      and lymphoma after chemotherapy, it is known to occur in solid malignancies. We
      herein report a rare case of this syndrome after resection of bulky carcinoid
      tumor of the lung.

PMID- 30218666
TI  - Innate Immune Cells Regulate Oncoimmunity and Cancer Development.

PMID- 30218667
TI  - Roles for Interleukin 17 and Adaptive Immunity in Pathogenesis of Colorectal
      Cancer.
AB  - Sporadic colorectal cancer is one of the most common and lethal cancers
      worldwide. The locations and functions of immune cells in the colorectal tumor
      microenvironment are complex and heterogeneous. T-helper (Th)1 cell-mediated
      responses against established colorectal tumors are associated with better
      outcomes of patients (time of relapse-free or overall survival), whereas Th17
      cell-mediated responses and production of interleukin 17A (IL17A) have been
      associated with worse outcomes of patients. Tumors that develop in mouse models
      of colorectal cancer are rarely invasive and differ in many ways from human
      colorectal tumors. However, these mice have been used to study the mechanisms by
      which Th17 cells and IL17A promote colorectal tumor initiation and growth, which
      appear to involve their direct effects on colon epithelial cells. Specific
      members of the colonic microbiota may promote IL17A production and IL17A
      producing cell functions in the colonic mucosa to promote carcinogenesis.
      Increasing our understanding of the interactions between the colonic microbiota
      and the mucosal immune response, the roles of Th17 cells and IL17 in these
      interactions, and how these processes are altered during colon carcinogenesis,
      could lead to new strategies for preventing or treating colorectal cancer.

PMID- 30218668
TI  - Full-field Optical Coherence Tomography: A New Imaging Modality for Rapid On-Site
      Evaluation of Resected Polyps During Colonoscopy.

PMID- 30218669
TI  - Detection and Analysis of Circulating Epithelial Cells in Liquid Biopsies From
      Patients With Liver Disease.

PMID- 30218670
TI  - Detecting differences with magnetoencephalography of somatosensory processing
      after tactile and electrical stimuli.
AB  - BACKGROUND: Deviant stimuli within a standard, frequent stimulus train induce a
      cortical somatosensory mismatch response (SMMR). The SMMR reflects the brain's
      automatic mechanism for the detection of change in a somatosensory domain. It is
      usually elicited by electrical stimulation, which activates nerve fibers and
      receptors in superficial and deep skin layers, whereas tactile stimulation is
      closer to natural stimulation and activates uniform fiber types. We recorded
      SMMRs after electrical and tactile stimuli. METHOD: 306-channel
      magnetoencephalography recordings were made with 16 healthy adults under two
      conditions: electrical (eSMMR) and tactile (tSMMR) stimulations. The SMMR
      protocol consisted of 1000 stimuli with 10% deviants to fingers. RESULTS: Sensor
      level analysis revealed stronger activation after deviant stimulation in
      bilateral channel locations approximately corresponding to parietal cortical
      areas within both stimulation conditions. Between conditions, deviant tSMMR
      showed stronger activation in the ipsilateral channels. Based on sensor-level
      results, two components, M50 and SMMR (40-58 and 110-185 ms), were compared at
      the source-level. Deviant stimulation elicited stronger contralateral SI
      activation during M50 component in both conditions. SMMR was observed with both
      conditions, activating contralateral SII after deviant stimulation. However, only
      tSMMR showed long latency activation in bilateral SI cortices. This suggests that
      there is an integration of both body sides during the automatic stages of tactile
      processing in SI cortices. CONCLUSIONS: This study indicates that tactile
      stimulation (tSMMR) is a feasible method for investigating the brain's mechanism
      for detecting somatosensory changes; this may extend the clinical utility of
      tSMMR for assessing disorders involving altered somatosensory processing.

PMID- 30218671
TI  - Effect of reperfusion on vascular smooth muscle reactivity in three contraction
      models.
AB  - BACKGROUND: Ischemia and reperfusion remain inseparable elements of numerous
      medical procedures such as by-pass surgery, organ transplantation or other
      cardiology and intervention radiology. The contraction of the smooth muscle of
      the vessel is considered to be one of the basic components leading to impaired
      perfusion, an increase in the oxygen deficit of the endothelium of the vessel,
      and subsequently also to tissues vascularized by the vessel. Main aim of this
      study was to evaluate the effect of ischemia and reperfusion on vascular smooth
      muscle cells stimulated pharmacologically with mastoparan-7 (direct G-protein
      activator) in comparison to stimulation of G-protein coupled receptor agonist -
      phenylephrine, and direct calcium channel activator - Bay K8644. MATERIAL AND
      METHODS: Experiments were performed on isolated and perfused tail artery of
      Wistar rats. Contraction force in our model was measured by increased level of
      perfusion pressure with a constant flow. RESULTS: Concentration-response curves
      obtained for phenylephrine, mastoparan-7 and Bay K8644 presented a sigmoidal
      relation. Ischemia induced hyporreactivity of vessels, whereas during reperfusion
      the significant time related hyperreactivity for phenylephrine and mastoparan-7
      only but not for Bay K8644. These reactions were secondary to the modulation of
      calcium influx from intra- and extracellular calcium stores. CONCLUSIONS: Results
      of our experiments suggest that mastoparan-7 significantly induces contraction of
      vascular smooth muscle cells not only for controls but in the presence of
      ischemia and reperfusion too. Potential therapeutic applications of the observed
      reactions are important. They may include regenerative processes within the
      nervous system, studies on the improvement of blood flow within the
      microcirculation, or antimicrobial activity. Modulation of the G protein
      phospholipase C response may also be an interesting point of action of future
      drugs modifying the response to stimulation during ischemia in particular, such
      activities could take place during the transport of organs for transplantation.

PMID- 30218672
TI  - The effects of donepezil on phencyclidine-induced cognitive deficits in a mouse
      model of schizophrenia.
AB  - Donepezil is the first-line of treatment for Alzheimer's disease (AD), which
      improves cognitive impairment effectively, but whether it has an impact on
      cognitive impairment in schizophrenia remains unknown. In this study, we
      evaluated the effects and mechanisms of donepezil on schizophrenia-like cognitive
      deficits induced by phencyclidine (PCP). The cognitive deficits model of
      schizophrenia was established by injecting PCP into mice. Risperidone, an
      atypical antipsychotic drug, served as positive control drug. Three behavioral
      tests including novel object recognition (NOR) test, Morris Water Maze (MWM) and
      passive avoidance (PA) test were performed to evaluate the effect of donepezil on
      PCP-induced cognitive deficits. Furthermore, the content of BDNF and NGF in the
      hippocampus and cortex of mice was determined using ELISA. Expressions of p-GSK
      3beta/GSK-3beta, p-Akt/Akt, Bcl-2/Bax and Caspase-3 in the hippocampus and cortex
      were detected by Western blot. Results revealed that donepezil has a protective
      effect on PCP-induced cognitive dysfunction. Moreover, donepezil can also improve
      PCP-induced schizophrenia-like cognitive deficits by inhibiting neuronal
      apoptosis and regulating synaptic plasticity, which was possible through the up
      regulation of p-Akt, p-GSK-3beta, Bcl-2 and the down-regulation of Bax, Caspase
      3. The results indicated that donepezil might exhibit a beneficial effect on the
      treatment of cognitive dysfunction in schizophrenia.

PMID- 30218673
TI  - Opioid modulation of social play reward in juvenile rats.
AB  - Social play behaviour is a vigorous form of social interaction abundant during
      the juvenile and adolescent phases of life in many mammalian species, including
      rats and humans. Social play is thought to be important for social, emotional and
      cognitive development. Being a rewarding activity, the expression of social play
      depends on its pleasurable and motivational properties. Since opioids have been
      widely implicated in reward processes, in the present study we investigated the
      role of opioids in the pleasurable and motivational properties of social play
      behaviour in rats. To assess social play motivation, an operant conditioning
      setup was used in which rats responded for social play under a progressive ratio
      schedule of reinforcement. Treatment with the opioid receptor agonist morphine
      reduced responding for social play at the highest dose tested, likely due to its
      rate-limiting effects. Morphine treatment increased the expression of social play
      behaviour during reinforced periods. The acquisition of social play-induced
      conditioned place preference (CPP) in a subeffective conditioning protocol was
      enhanced by treatment with morphine. Morphine treatment alone also induced CPP.
      In contrast, antagonizing opioid receptors with naloxone reduced responding for
      social play, the expression of social play and blocked the development of social
      play-induced CPP. These data implicate opioid neurotransmission in both the
      pleasurable and the motivational aspects of social play behaviour in rats.

PMID- 30218674
TI  - Andrographolide ameliorates intracerebral hemorrhage induced secondary brain
      injury by inhibiting neuroinflammation induction.
AB  - Microglia activation and neuroinflammation play important roles in intracerebral
      hemorrhage (ICH)-induced secondary brain injury (SBI). In this study, we
      attempted to investigate the potential effects of Andrographolide (Andro) on ICH
      induced SBI and the possible mechanisms behind these effects. Andro treatment
      effectively reduced neuronal cell death and degeneration and alleviated
      neurobehavioral disorders and brain edema in vivo. In an in vitro study,
      microglia activation-induced neuronal cell death was ameliorated by Andro
      treatment. In addition, microglia activation and neuroinflammation were induced
      by ICH, exhibiting elevated cytokine levels, which could be reversed with Andro
      treatment. The levels of TNF-alpha and IL-6 were significantly decreased after
      treatment with Andro, both in vivo and in vitro, due to the inhibition of nuclear
      transcription factor-kappaB (NF-kappaB) signaling pathway activation. Meanwhile,
      Andro decreased the levels of IL-1beta and LDH, as well as microglia pyroptosis
      induced by ICH by suppressing the assembly of the nucleotide-binding
      oligomerization domain like receptor protein 3 (NLRP3) inflammasome. In summary,
      this study reveals an anti-inflammatory effect of Andro and its potential
      mechanisms, and it shows that Andro is a potential candidate for improving ICH
      induced SBI.

PMID- 30218675
TI  - Next-generation anti-Staphylococcus aureus vaccines: A potential new therapeutic
      option for atopic dermatitis?

PMID- 30218676
TI  - Comparison of a new Skin Prick Test Tape with the conventional skin prick test.

PMID- 30218677
TI  - Hematopoietic stem cell transplantation for activated phosphoinositide 3-kinase
      delta syndrome: Who, when, and how?

PMID- 30218678
TI  - Exploring cellular fatty acid composition and intracellular metabolites of
      osmotic-tolerant mutant Lactobacillus paracasei NCBIO-M2 for highly efficient
      lactic acid production with high initial glucose concentration.
AB  - High titer, productivity and yield are the main pre-requisites of an efficient
      lactic acid production process. However, the hyperosmotic stress inhibits cell
      metabolism in the later phase of fermentation. In this study, an osmotic-tolerant
      mutant named Lactobacillus paracasei NCBIO01-M2 was obtained through a high
      throughput screening technology, which exhibited a higher tolerance to osmotic
      stress due to its more flexible regulation of the unsaturated fatty acid
      proportion along with the intracellular compatible solute pools. The mutant
      successfully consumed all 248 g/L initial glucose and produced 223.7 g/L lactic
      acid with a productivity of 5.53 g/L/h in a single batch fermentation by the
      neutralizing agent strategy. Moreover, similar fermentation performances were
      also achieved in the open fermentation mode without sterilization by the mutant,
      which suggested that the mutant would be a potential for cost-effective
      commercial lactic acid production.

PMID- 30218679
TI  - MicroRNA-378 promotes hepatic inflammation and fibrosis via modulation of the NF
      kappaB-TNFalpha pathway.
AB  - BACKGROUND & AIMS: The progression of hepatosteatosis to non-alcoholic
      steatohepatitis (NASH) is a critical step in the pathogenesis of hepatocellular
      cancer. However, the underlying mechanism(s) for this progression is essentially
      unknown. This study was designed to determine the role of miR-378 in regulating
      NASH progression. METHODS: We used immunohistochemistry, luciferase assays and
      immunoblotting to study the role of miR-378 in modulating an inflammatory
      pathway. Wild-type mice kept on a high-fat diet (HFD) were injected with miR-378
      inhibitors or a mini-circle expression system containing miR-378, to study loss
      and gain-of functions of miR-378. RESULTS: MiR-378 expression is increased in
      livers of dietary obese mice and patients with NASH. Further studies revealed
      that miR-378 directly targeted Prkag2 that encodes AMP-activated protein kinase
      gamma 2 (AMPKgamma2). AMPK signaling negatively regulates the NF-kappaB-TNFalpha
      inflammatory axis by increasing deacetylase activity of sirtuin 1. By targeting
      Prkag2, miR-378 reduced sirtuin 1 activity and facilitated an inflammatory
      pathway involving NF-kappaB-TNFalpha. In contrast, miR-378 knockdown induced
      expression of Prkag2, increased sirtuin 1 activity and blocked the NF-kappaB
      TNFalpha axis. Additionally, knockdown of increased Prkag2 offset the inhibitory
      effects of miR-378 inhibitor on the NF-kappaB-TNFalpha axis, suggesting that AMPK
      signaling mediates the role of miR-378 in facilitating this inflammatory pathway.
      Liver-specific expression of miR-378 triggered the development of NASH and
      fibrosis by activating TNFalpha signaling. Ablation of TNFalpha in miR-378
      treated mice impaired the ability of miR-378 to facilitate hepatic inflammation
      and fibrosis, suggesting that TNFalpha signaling is required for miR-378 to
      promote NASH. CONCLUSION: MiR-378 plays a key role in the development of hepatic
      inflammation and fibrosis by positively regulating the NF-kappaB-TNFalpha axis.
      MiR-378 is a potential therapeutic target for the treatment of NASH. LAY SUMMARY:
      The recent epidemic of obesity has been associated with a sharp rise in the
      incidence of non-alcoholic fatty liver disease (NAFLD). However, the underlying
      mechanism(s) remains poorly described and effective therapeutic approaches
      against NAFLD are lacking. The results establish that microRNA-378 facilitates
      the development of hepatic inflammation and fibrosis and suggests the therapeutic
      potential of microRNA-378 inhibitor for the treatment of NAFLD.

PMID- 30218680
TI  - Generalized seizures evoked by nucleus accumbens stimulation induced an opiate
      mediated suppression of psychosis relevant behaviors.
AB  - We have previously demonstrated that kindling of the nucleus accumbens (NAc)
      induced psychosis relevant behaviors only after one, but not after five, stage-5
      seizures, suggesting that five stage-5 NAc-evoked seizures antagonized psychosis
      relevant behaviors in rats. We hypothesized that brain opioid receptors are
      responsible for seizure-induced reduction of psychosis relevant behaviors in NAc
      kindled rats. Rats received NAc kindling until a stage-4 seizure was induced,
      after which naloxone, a non-specific opioid receptor antagonist, at dose of 1 or
      10 mg/kg i.p., or saline (0.3 mL) i.p., was injected 15 min before each kindled
      seizure. Duration of afterdischarge (AD) was not significantly different among
      naloxone- and saline-treated groups. However, duration of postictal behavioral
      depression induced by a stage-5 seizure was significantly shorter in 10 mg/kg
      naloxone-treated than saline-treated rats, for long (>36 s) AD duration. When
      tested 3-4 days after five stage-5 seizures, 10 mg/kg naloxone-treated rats, as
      compared to saline-treated rats, showed a statistically significant loss of
      gating of hippocampal auditory evoked potentials, and significant reduction of
      startle response amplitude, but non-significant differences in prepulse
      inhibition and methamphetamine-induced locomotion. It is inferred that stage-5
      seizures, by releasing endogenous opiates, contribute to postictal behavioral
      depression, and some long-term seizure-induced antipsychotic effects.

PMID- 30218681
TI  - Graphene oxide nano-bio interaction induces inhibition of spermatogenesis and
      disturbance of fatty acid metabolism in the nematode Caenorhabditis elegans.
AB  - Graphene oxide (GO) has the potential for wide applications, which necessitates
      an intensive investigation of its potential hazard on human and environmental
      health. Even if previous studies show reproductive toxicity in the nematode
      Caenorhabditis elegans, the mechanisms of reproductive toxicity by GO are poorly
      understood. To understand the underlying mechanisms of GO-induced reproductive
      toxicity, we investigated the interaction between GO and C. elegans using Raman
      spectroscopy, sperm counts produced by spermatogenesis, progeny and analyzed the
      fatty acid metabolism using molecular techniques. GO-characteristic Raman
      spectral bands measured throughout C. elegans, brood size and Hoecst staining of
      dissected gonads clearly showed GO accumulation in the reproductive organs,
      reduced progeny and low sperm counts, which are possibly direct results of the
      reproductive toxicity from GO exposure. Interestingly, reduced fatty acid
      metabolites, such as stearic, oleic, palmitoleic, and palmitic acids, were found
      with GO exposure. We found that GO increased intestinal fat accumulation in wild
      type N2, fat-5(tm420), and fat-7(wa36) mutants, whereas it decreased fat storage
      in the fat-6(tm331) and nhr-49(nr2041) mutants. GO exposure affected C. elegans
      fat accumulation and consumption, which was possibly regulated by daf-16 and nhr
      80 gene activity. Also, GO exposure suppressed the survival of long-lived fat
      5(tm420) mutants, whereas it increased the survival of short-lived nhr-49(nr2041)
      mutants. Hence, our studies collectively indicated that GO accumulation in
      reproductive organs, suppression of spermatogenesis, and the alteration of fatty
      acid metabolism play critical roles in understanding mechanisms of toxicity in C.
      elegans.

PMID- 30218682
TI  - Superior efficacy of HI-6 dimethanesulfonate over pralidoxime methylsulfate
      against Russian VX poisoning in cynomolgus monkeys (Macaca fascicularis).
AB  - Organophosphorus nerve agents still represent a serious risk to human health. In
      the French armed forces, the current emergency treatment against OP intoxications
      is a fully licensed wet-dry dual-chambered autoinjector (Ineurope (r)), that
      contains pralidoxime methylsulfate (2-PAM) to reactivate inhibited
      acetylcholinesterase (AChE), atropine sulfate (AS) and avizafone chlorhydrate
      (AVZ). While this treatment is effective against several of the known nerve
      agents, it shows little efficacy against the Russian VX (VR), one of the most
      toxic compounds. HI-6 dimethanesulfonate (HI-6 DMS) is an oxime able to
      reactivate in vitro and in vivo VR-inhibited AChE. To confirm the superiority of
      HI-6 DMS towards 2-PAM prior to licensing, we compared the two 3-drug
      combinations (HI-6 vs 2-PAM, 33 and 18 mg/kg respectively, equimolar doses;
      AS/AVZ 0.25/0.175 mg/kg respectively) in VR-poisoned cynomolgus macaques, the
      model required by the French drug regulatory agency. In parallel we performed HI
      6 pharmacokinetics analysis using a one compartment model. A better efficacy of
      the HI-6 DMS combination was clearly observed: up to 5 LD50 of VR (i.m.), a
      single administration of the HI-6 DMS combination, shortly after the onset of
      clinical signs, prevented death of the four intoxicated animals. Conversely 2-PAM
      only prevented death in one out of three subjects exposed to the same amount of
      VR. As expected with V agents, reinhibition of blood AChE was observed but
      without any apparent impact on the clinical recovery of the animals. A single
      administration of the HI-6 DMS combination was still but partially effective at
      15 LD50 of VR, allowing a 50% survival rate.

PMID- 30218683
TI  - WITHDRAWN: Toxic effects of gestational arsenic trioxide on the neuroendocrine
      axis of developing rats.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 30218684
TI  - A convenient colorimetric assay for the quantification of porcine epidemic
      diarrhea virus and neutralizing antibodies.
AB  - Neonatal enteritis caused by the porcine epidemic diarrhea virus (PEDV) is an
      important cause of high mortality and economic losses to the swine industry.
      Virus neutralization (V/N) assays are commonly requested in diagnostic
      laboratories for the assessment of protective antibodies. However, the visual
      assessment of viral cytopathic effects by operators to determine antibody titers
      or for viral quantification is a tedious, subjective and time-consuming process,
      especially when high volume testing is involved. To improve the ease of testing,
      a colorimetric virus neutralization and TCID50 assays were developed and
      validated in this study using (3-(4,5-dimethylthiazol-2-yl) Tr-2,5
      diphenyltetrazolium- bromide) (MTT), a colorimetric agent which measures cell
      viability. The respective conventional assays were used as the gold standards. An
      OD cut off value of <=0.53, selected by receiver operating characteristics
      analysis, could distinguish between wells with and without CPE accurately.
      Performance and reproducibility parameters of the colorimetric assays were
      comparable to the conventional assays. The described methods can reduce testing
      time in diagnostic laboratories, while significantly improving current protocols.

PMID- 30218685
TI  - A Fond Salute to George Stamatoyannopoulos - Scholar Leader Mentor Colleague
      Friend.

PMID- 30218686
TI  - Optimal control strategies for dengue transmission in pakistan.
AB  - This paper presents a deterministic model for dengue virus transmission. The
      model is parameterized using data from the 2017 dengue outbreak in Pakistan. We
      estimated the basic reproduction number (R0) without any interventions for the
      2017 dengue outbreak in Peshawar district of Pakistan as R0~2.64, the
      distribution of the reproduction number lies in the range R0?[1.21,5.24] (with a
      mean R0~2.64). Optimal control theory is then applied to investigate the optimal
      strategy for curtailing the spread of the disease using two time-dependent
      control variables determined from sensitivity analysis. These control variables
      are insecticide use and vaccination. The results show that the two controls avert
      the same number of infections in the district regardless of the weights on the
      costs this is due to the reciprocal relationship between the cost of insecticide
      use and vaccination. A strong reciprocal relationship exists between the use of
      insecticide and vaccination; as the cost of insecticide increases the use of
      vaccination increases. The use of insecticide on the other hand slightly
      increases when vaccination level decreases due to increase in cost.

PMID- 30218687
TI  - Advax augments B and T cell responses upon influenza vaccination via the
      respiratory tract and enables complete protection of mice against lethal
      influenza virus challenge.
AB  - Administration of influenza vaccines via the respiratory tract has potential
      benefits over conventional parenteral administration, inducing immunity directly
      at the site of influenza exposure as well as being needle free. In this study, we
      investigated the suitability of AdvaxTM, a stable particulate polymorph of
      inulin, also referred to as delta inulin, as a mucosal adjuvant for whole
      inactivated influenza vaccine (WIV) administered either as a liquid or dry powder
      formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles
      in a size range (1-5 MUm) suitable for inhalation. The physical and biological
      characteristics of both WIV and Advax remained unaltered both by admixing WIV
      with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization,
      both liquid and dry powder formulations containing Advax induced significantly
      higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV
      formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led
      to robust memory B cell responses along with an increase of lung localization
      factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect
      of Advax was seen on memory T cell responses. In contrast to animals immunized
      with WIV alone, all animals pulmonary immunized with a single dose of Advax
      adjuvanted WIV were fully protected with no visible clinical symptoms against a
      lethal dose of influenza virus. These data confirm that Advax is a potent mucosal
      adjuvant that boosts vaccine-induced humoral and cellular immune responses both
      in the lung and systemically with major positive effects on B-cell memory and
      complete protection against live virus. Hence, respiratory tract immunization,
      particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or
      dry powder is a promising alternative to parenteral influenza vaccination.

PMID- 30218689
TI  - The heartbeat counting task largely involves non-interoceptive processes:
      Evidence from both the original and an adapted counting task.
AB  - The heartbeat counting task (HCT) is among the most frequently used measures of
      interoceptive accuracy (i.e., IAcc). Growing concerns, however, have been raised
      regarding the validity of this task, as well as the validity of the IAcc scores
      that are derived from it. In the present study, healthy participants (N = 123)
      performed both the original task and an adapted version of it that stressed the
      importance of reporting only their perceptually felt heartbeats. In the original
      task, we found that participants report relying on three different strategies
      (i.e., detection of heartbeats in a specific body location, detection of
      heartbeats in a diffuse way and heart rate estimation) to complete the task. In
      the adapted task, we found that IAcc scores are drastically reduced (about 50%)
      when asking participants to avoid relying on non-interoceptive signals and to
      only report the heartbeats they perceive. These findings confirm that the HCT
      task is largely contaminated by the influence of non-interoceptive processes.
      Implications of these findings for research on interoception are discussed.

PMID- 30218688
TI  - Pan-HER-targeted approach for cancer therapy: Mechanisms, recent advances and
      clinical prospect.
AB  - The Human Epidermal Growth Factor Receptor family is composed of 4 structurally
      related receptor tyrosine kinases that are involved in many human cancers. The
      efficacy and safety of HER inhibitors have been compared in a wide range of
      clinical trials, suggesting the superior inhibitory ability of multiple- HER
      targeting blockade compared with single receptor antagonists. However, many
      patients are currently resistant to current therapeutic treatment and novel
      strategies are warranted to conquer the resistance. Thus, we performed a critical
      review to summarize the molecular involvement of HER family receptors in tumour
      progression, recent anti-HER drug development based on clinical trials, and the
      potential resistance mechanisms of anti-HER therapy.

PMID- 30218690
TI  - Multitasking in aging: ERP correlates of dual-task costs in young versus low,
      intermediate, and high performing older adults.
AB  - With large inter-individual variability, older adults show a decline in cognitive
      performance in dual-task situations. Differences in attentional processes,
      working memory, response selection, and general speed of information processing
      have been discussed as potential sources of this decline and its between-subject
      variability. In comparison to young subjects (n = 36, mean age: 25 years), we
      analyzed the performance of a large group of healthy elderly subjects (n = 138,
      mean age: 70 years) in a conflicting dual-task situation (PRP paradigm). Based on
      their dual-task costs (DTCs), the older participants were clustered in three
      groups of high, medium, and low performing elderly. DTCs differed between groups
      and increased linearly from young subjects to low performing elderly. The groups
      did not differ with respect to ERP-components related to task preparation (CNV)
      and recall of stimulus-response mappings (P2). Peak latencies of the
      frontocentral P2 and N2 were shorter in young as compared to older adults but did
      not differ between elderly performance groups. However, differences in N2
      amplitude between short and long SOA were correlated with the corresponding DTCs,
      suggesting more efficient S-R implementation in subjects with lower DTCs. Based
      on our results, between-subject differences in dual-task interference can be
      explained in terms of individual differences in selection of an appropriate
      response in dual-task situations.

PMID- 30218691
TI  - Genomic sequence of a novel endornavirus from Phaseolus vulgaris and occurrence
      in mixed infections with two other endornaviruses.
AB  - The Endornaviridae family includes viruses with ssRNA genome that infect plants,
      fungi, and oomycetes. Plant endornaviruses do not cause visible symptoms and are
      transmitted only vertically. Many common bean (Phaseolus vulgaris) genotypes have
      been reported to be infected by Phaseolus vulgaris endornavirus 1 and Phaseolus
      vulgaris endornavirus 2. Using next-generation sequencing, we obtained the RNA
      sequence of a third common bean endornavirus, which we named Phaseolus vulgaris
      endornavirus 3 (PvEV3). The complete sequence consisted of 15,205nt in length
      with a single open reading frame (ORF) coding for a polyprotein of 4932 aa, and
      untranslated regions of 344ont and 62ont at the 5' and 3' ends respectively. The
      polyprotein contained conserved protein domains including viral helicase 1,
      peptidase C97, glycosyltransferases of the GTB-type, and RdRp 2. The polyprotein
      shared 31% amino acid identity with the counterpart encoded by Hordeum vulgare
      endornavirus. A phylogenetic tree constructed with the RdRp sequences of PvEV3
      and other endornaviruses placed PvEV3 in a clade with members of the genus
      Alphaendornavirus. PvEV3 was detected in cultivated and wild P. vulgaris
      genotypes as single and mixed infections with two other common bean
      endornaviruses. The natural occurrence of three distinct endornaviruses in a
      single plant species is unique and has not been reported in other plant
      endornavirus systems.

PMID- 30218692
TI  - Transurethral Enucleation With Bipolar Energy (TUEB):AINU Technique and Short
      term Outcomes.
AB  - OBJECTIVE: To present our transurethral enucleation with bipolar energy (TUEB)
      technique, wherein the enucleated adenoma is resected while keeping it attached
      near the verumontanum avoiding the need of a morcellator, and to evaluate the
      safety and short-term outcomes of our technique of TUEB for the treatment of
      symptomatic benign prostatic hypertrophy (BPH). METHODS: This was a retrospective
      evaluation of prospectively maintained database of patients with symptomatic BPH
      who underwent TUEB from January 2016 to September 2017. Patients with a minimum
      follow-up period of 6 months were included in the study. All patients were
      assessed using the international prostate symptom score (IPSS), uroflometry (Q
      max), and transrectal ultrasonography (TRUS) of the prostate. TUEB was indicated
      for patients with total prostate volumes >60 g on TRUS. Postoperative outcome
      measures, including urinary incontinence, Q-max, and IPSS, were recorded at each
      follow-up visit. RESULTS: A total of 103 patients underwent TUEB. The mean
      patient age was 64 +/- 7 years, and the median operative time was 54 minutes
      (interquartile range [IQR]: 44-66). The median resected prostate weight was 39 g
      (IQR: 28-54 g), corresponding to approximately 87% of the assessed transitional
      zone volume. The mean postoperative hemoglobin drop of 1.08 +/- 0.28 g/dL was
      clinically insignificant. There was significant improvement in the IPSS and Q-max
      postoperatively, when compared to baseline parameters (P < .05). CONCLUSION: Our
      TUEB technique is safe and effective in treating symptomatic BPH with acceptable
      complications and favorable short-term outcomes. TUEB allows near-complete
      enucleation of a prostate adenoma, followed by resection, thus avoiding the need
      for a morcellator.

PMID- 30218693
TI  - Ghrelin attenuates myocardial fibrosis after acute myocardial infarction via
      inhibiting endothelial-to mesenchymal transition in rat model.
AB  - Ghrelin, a peptide hormone produced in the gastrointestinal tract, has recently
      been found to be associated with the onset of myocardial fibrosis (MF). The exact
      mechanism, however, remains elusive. This study sought to identify the function
      and mechanism of ghrelin on MF after acute myocardial infarction (AMI). AMI was
      established in Spraque-Dawley rats by ligation of the left anterior descending
      (LAD). Ghrelin or saline was intraperitoneally injected two times per day for 8
      weeks after ligation. The weight of heart (mg) and the weight ratio of heart to
      body (mg/g) as well as the fibrotic area were increased, while serum level of
      ghrelin was decreased after AMI. Ghrelin significantly ameliorated MF and
      decreased deposition of collagens in perivascular fibrosis area. In addition,
      ghrelin inhibited Endothelial-to-mesenchymal transition (EndMT), a crucial
      process for MF, in perivascular fibrosis area and TGF-beta1-induced human
      coronary artery endothelial cells (HCAECs). Mechanistically, ghrelin persistently
      decreased the phosphorylation of Smad2/3 and enhanced the expression of Smad7 and
      p-AMPK in vivo and in vitro. After the abolition of Smad7, GHSR-1a and AMPK
      pathway, the effect of ghrelin on EndMT was significantly inhibited. In
      conclusion, these results presented a novel finding that ghrelin attenuated MF
      after AMI via regulation EndMT in a GHSR-1a/AMPK/Smad7- dependent manner.

PMID- 30218695
TI  - Pharmacokinetics and safety of a single dose of the novel LAMA/LABA fixed-dose
      combination of glycopyrronium/formoterol fumarate dihydrate metered dose inhaler,
      formulated using co-suspension delivery technology, in Japanese healthy subjects.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes significant
      mortality in Japan. GFF MDI is a long-acting muscarinic antagonist/long-acting
      beta2-agonist fixed-dose combination of glycopyrronium (GP) and formoterol
      fumarate dihydrate (FF), delivered by a metered dose inhaler (MDI) using co
      suspension delivery technology, for the long-term maintenance treatment of COPD.
      METHODS: This randomized, Phase I, single-dose, four-treatment, four-period,
      crossover study (NCT02196714) examined the pharmacokinetic (PK) and safety
      profile of two doses of GFF MDI (28.8 MUg/10 MUg and 14.4 MUg/10 MUg) and two
      doses of GP MDI (28.8 MUg and 14.4 MUg), both formulated using co-suspension
      delivery technology, in healthy Japanese subjects (18-45 years of age). PK
      parameters included area under the curve (AUC) from 0 to 12 h (AUC0-12), AUC from
      0 to the time of the last measurable plasma concentration, maximum observed
      plasma concentration (Cmax), and time to Cmax. Safety was monitored throughout
      the study. RESULTS: Plasma GP profiles were comparable between GFF MDI and GP MDI
      formulations containing the same GP dose. Increases in GP AUC0-12 and Cmax were
      generally dose proportional from 14.4 to 28.8 MUg after administration of either
      formulation. CONCLUSIONS: The addition of FF 10 MUg to GP MDI 28.8 MUg or 14.4
      MUg in a fixed-dose combination did not appreciably alter the PK of GP, nor did
      an increase in GP dose from 14.4 MUg to 28.8 MUg in a fixed-dose combination with
      FF 10 MUg appreciably alter the PK of formoterol. Both formulations of GFF MDI
      and GP MDI were well tolerated in healthy Japanese subjects. Data from this study
      support further evaluation of GFF MDI in Japanese patients with COPD.

PMID- 30218694
TI  - Towards rationally designed biomanufacturing of therapeutic extracellular
      vesicles: impact of the bioproduction microenvironment.
AB  - Extracellular vesicles (EVs), including exosomes, microvesicles, and others, have
      emerged as potential therapeutics for a variety of applications. Pre-clinical
      reports of EV efficacy in treatment of non-healing wounds, myocardial infarction,
      osteoarthritis, traumatic brain injury, spinal cord injury, and many other
      injuries and diseases demonstrate the versatility of this nascent therapeutic
      modality. EVs have also been demonstrated to be effective in humans, and clinical
      trials are underway to further explore their potential. However, for EVs to
      become a new class of clinical therapeutics, issues related to translation must
      be addressed. For example, approaches originally developed for cell
      biomanufacturing, such as hollow fiber bioreactor culture, have been adapted for
      EV production, but limited knowledge of how the cell culture microenvironment
      specifically impacts EVs restricts the possibility for rational design and
      optimization of EV production and potency. In this review, we discuss current
      knowledge of this issue and delineate potential focus areas for future research
      towards enabling translation and widespread application of EV-based therapeutics.

PMID- 30218696
TI  - Soup with or without meatballs: Impact of nutritional factors on the MIC, kill
      rates and growth-rates.
AB  - BACKGROUND: The Minimum Inhibitory Concentration (MIC) is a reference value for
      susceptibility testing of bacteria. However, the MIC is a net result of growth
      and killing after a certain duration of exposure under standardized favourable in
      vitro conditions. Killing and growth characteristics of a drug may yield more
      information on its activity and help to explain discrepancies between efficacy
      observed in vitro and in vivo. METHODS: The MIC of meropenem was determined for
      P. aeruginosa ATCC 27853 both by microdilution and the E-test in dilutions of
      Mueller Hinton (MH) broth from 100% to 1%. Time-kill curves were obtained for
      twofold dilutions of meropenem. Growth rates and kill rates at each concentration
      and dilution were obtained by linear regression. The Hill equation was fit to the
      kill rates vs concentrations. RESULTS: Growths rates decreased log linearly from
      0.63/h at 100% to 0.29/h at 6% MH. Over the 100-6% MH dilution range, there was a
      log-linear decrease of the MIC of meropenem of both the E-test and microdilution.
      The EC50s decreased from 0.29 mg/L to 0.07 mg/L, which is in agreement with the
      MIC results. There was a log-linear relationship between MIC and EC50 for the
      various dilutions MH. CONCLUSIONS: The availability of nutritional factors is
      related to the MIC, and a lower availability is related to both a lower growth
      rate and higher kill rate. Since nutritional factors are less abundantly
      available in vivo as compared to in vitro, this should be taken into account when
      translating in vitro to in vivo pharmacodynamics.

PMID- 30218697
TI  - Di-n-butyl phthalate modifies PMA-induced macrophage differentiation of THP-1
      monocytes via PPARgamma.
AB  - The present study examined the effects of di-n-butyl phthalate (DBP) on phorbol
      myristate acetate (PMA)-induced macrophage differentiation of THP-1 monocytes,
      determined by morphological classification and flow cytometry. Focusing on the
      expression of the surface marker CD36, the potential role of peroxisome
      proliferator-activated receptor gamma (PPARgamma) was examined using various
      PPARgamma agonists and antagonists. As the PPARgamma ligand-binding domain
      contains multiple ligand-binding sites (LBS), agonist and antagonists targeting
      the different sites were used. DBP accelerated PMA-induced morphological changes
      and increased expression of CD36, although to a lesser degree than the PPARgamma
      agonists rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2). A
      proteomics screening revealed that DBP enhanced the expression of PPARgamma
      regulated proteins. During combined exposures, DBP partly attenuated the effect
      of rosiglitazone, an agonist binding reversibly to PPARgamma's canonical LBS. In
      contrast, DBP increased expression of CD36 in combination with 15d-PGJ2 which
      binds irreversibly to the canonical LBS. Thus, DBP appears to interact with both
      the canonical and alternative LBS. Accordingly, the antagonist GW9662, which
      binds to the canonical LBS, only partly reduced the DBP-induced CD36 expression,
      while the dual-site antagonist SR16832 completely blocked the effects of DBP.
      Overall, the results show that DBP modifies PMA-induced differentiation of THP-1
      cells through interaction with PPARgamma.

PMID- 30218698
TI  - Assessing bioactivity-exposure profiles of fruit and vegetable extracts in the
      BioMAP profiling system.
AB  - The ToxCast program has generated in vitro screening data on over a thousand
      chemicals to assess potential disruption of important biological processes and
      assist in hazard identification and chemical testing prioritization. Few results
      have been reported for complex mixtures. To extend these ToxCast efforts to
      mixtures, we tested extracts from 30 organically grown fruits and vegetables in
      concentration-response in the BioMAP(r) assays. BioMAP systems use human primary
      cells primed with endogenous pathway activators to identify phenotypic
      perturbations related to proliferation, inflammation, immunomodulation, and
      tissue remodeling. Clustering of bioactivity profiles revealed separation of
      these produce extracts and ToxCast chemicals. Produce extracts elicited 87 assay
      endpoint responses per item compared to 20 per item for ToxCast chemicals. On a
      molar basis, the produce extracts were 10 to 50-fold less potent and when
      constrained to the maximum testing concentration of the ToxCast chemicals, the
      produce extracts did not show activity in as many assay endpoints. Using intake
      adjusted measures of dose, the bioactivity potential was higher for produce
      extracts than for agrichemicals, as expected based on the comparatively small
      amounts of agrichemical residues present on conventionally grown produce. The
      evaluation of BioMAP readouts and the dose responses for produce extracts showed
      qualitative and quantitative differences from results with single chemicals,
      highlighting challenges in the interpretation of bioactivity data and dose
      response from complex mixtures.

PMID- 30218699
TI  - The Importance of A, B, Cs! Airways and Breathing Matter for Survival after
      Hematopoietic Stem Cell Transplantation.

PMID- 30218700
TI  - Rare Diseases Inform Myocardial Phenotypes for Precision Medicine.

PMID- 30218701
TI  - Innovating in Your Practice: Overcoming Barriers to Create New Opportunities.

PMID- 30218702
TI  - Primary Follicular Lymphoma of Gallbladder Presenting as Multiple Polyps.

PMID- 30218703
TI  - Incorporating Advanced Practice Providers into Gastroenterology Practice.

PMID- 30218704
TI  - Reply.

PMID- 30218705
TI  - Growing and Retaining an Endoscopy Nurse.

PMID- 30218706
TI  - Prevalence and genotypes of Enterocytozoon bieneusi in pigs in southern China.
AB  - Enterocytozoon bieneusi is one of the most important causative agents of
      microsporidiosis, causing diarrhoea the symptoms of enteric disease in humans and
      animals. Although there is some information on the prevalence and genotypes of E.
      bieneusi in China, there is still a lack of data in pigs in southern China. In
      the present study, a total of 396 faecal specimens were collected from pigs in
      Zhejiang, Guangdong and Yunnan provinces in southern China, and were examined by
      nested PCR amplification of the ribosomal internal transcribed spacer (ITS) for
      the prevalence and genotypes of E. bieneusi. The overall prevalence of E.
      bieneusi in pigs was 31.57% (125/396), forming 15 genotypes, including 9 known
      genotypes (EbpC, EbpA, D, G, H, PigEBITS5, Henan-IV, KIN-1, CHS5) and 6 novel
      genotypes (GD1, ZJ1, ZJ2, YN1, YN2 and YN3), which were all clustered into Group
      1. Moreover, multilocus sequence typing (MLST) showed that 6, 3, 4 and 5 types
      were identified in MS1, MS3, MS7 and MS4 loci, respectively, representing four
      multilocus genotypes (MLGs), designated as MLGs novel-1 to novel-4 in the present
      study. This is the first detailed study of E. bieneusi using MLST in pigs in
      southern China, which extended information about the distribution of E. bieneusi
      genotypes in China.

PMID- 30218707
TI  - Th17 and Treg lymphocytes in obesity and Type 2 diabetic patients.
AB  - Assumption that the pathogenesis of obesity-associated type 2 diabetes (T2DM)
      encompasses inflammation and autoimmune aspects is increasingly recognized. In
      the state of obesity and T2DM, the imbalance of T helper 17 (Th17) cells and
      regulatory T (Treg) cells are observed. These alterations reflect a loss of T
      cell homeostasis, which may contribute to tissue and systemic inflammation and
      immunity in T2DM. In this review we will discuss the accumulating data supporting
      the concept that Th17/Treg mediated immune responses are present in obesity
      related T2DM pathogenesis, and provide evidences that restoration of Th17/Treg
      imbalance may be a possible therapeutic avenue for the prevention and treatment
      of T2DM and its complications.

PMID- 30218708
TI  - Knee extension rate of velocity development affects walking performance
      differently in men and women.
AB  - PURPOSE: Acceleration capacity affects physical function, but whether it
      differentially affects men versus women or weak versus strong individuals is less
      known. We investigated whether knee extension rate of velocity development (RVD,
      a measure of acceleration) is associated with walking performance independent of
      peak torque and whether the relationships differ in men versus women and in weak
      versus strong individuals. METHODS: Relationships of RVD with walking performance
      were assessed in 326 women and 365 men aged 26-96 years enrolled in the Baltimore
      Longitudinal Study of Aging. Tests included knee extension peak torque and RVD
      assessed during a 180 degrees .s-1 isokinetic strength test and four walking
      performance measures (usual-paced and fast-paced 6 m walks and 2.5 min usual
      paced and 400 m fast-paced walks). Sex-stratified linear regression models were
      adjusted for age, race, height, appendicular lean mass, fat mass, peak torque,
      knee pain, and RVD*peak torque interaction. RESULTS: In men, RVD was not
      independently associated with any walking performance measure (p > 0.05), and,
      for the 6 m-usual walk only, there was a significant RVD*peak torque interaction
      (p < 0.0001). In women, RVD was independently associated with usual-paced walks
      (p < 0.05) and there were significant RVD * peak torque interactions for all
      measures. Strength-specific analyses indicated that RVD was most associated with
      performance among weaker individuals. CONCLUSION: RVD is associated with walking
      performance in women, but less in men, and is most related to performance when
      strength is low. Strategies to accomplish motor tasks may be sex-specific. Future
      studies are needed to understand the mechanisms underlying such sex differences.

PMID- 30218710
TI  - Perforating Scar of Intrauterine Device with Subsequent Intramural Pregnancy and
      Uterine Rupture.

PMID- 30218709
TI  - Female Pelvic Floor Immersive Simulation: A Randomized Trial to Test the
      Effectiveness of a Virtual Reality Anatomic Model on Resident Knowledge of Female
      Pelvic Anatomy.
AB  - STUDY OBJECTIVE: To estimate the effect of a virtual reality (VR) anatomic model
      (VisCubeSX; VisBox, Inc., Saint Joseph, IL) on obstetrics and gynecology
      residents' knowledge of female pelvic floor anatomy compared with a traditional
      curriculum. DESIGN: Randomized controlled trial (Canadian Task Force
      classification I). SETTING: Academic obstetrics and gynecology resident training
      program. INTERVENTIONS: Traditional independent study curriculum versus
      traditional curriculum and VisCubeSX VR curriculum MEASUREMENTS AND MAIN RESULTS:
      Residents were randomized, stratified by year of training, in a 1:1 fashion to
      traditional independent study curriculum for pelvic anatomy versus traditional
      curriculum and the VisCubeSX VR anatomic model. Tests were administered to assess
      baseline and postintervention knowledge. A postintervention assessment of the
      VisCubeSX VR anatomic model was performed. Baseline, follow-up, and score
      improvement were compared between groups using Student t tests and Wilcoxon rank
      sum tests. Thirty-one residents were randomized. There was a significant
      improvement in pre- and post-test scores within traditional independent study
      curriculum participants, 8.1 +/- 12.0 points (p = .02), and the VisCubeSX group
      8.7 +/- 6.4 points (p <.001), but these improvements did not differ between
      groups (p = .86). This lack of between-group differences was consistent in
      resident year-stratified analyses. Residents exposed to the VisCubeSX VR anatomic
      model reported they "somewhat" or "strongly agree" (15/16 [93.8%] and 14/16
      [87.5%] of residents, respectively) that the model improved their knowledge of
      pelvic anatomy and that the model will improve patient care. CONCLUSION: Few
      studies exist that compare educational outcomes of a traditional independent
      study of female pelvic anatomy curriculum versus immersive simulation with VR
      models in female pelvic anatomy. Knowledge scores were not significantly
      increased with the VR model compared with traditional curriculum, but VR
      technology was perceived as an enhancement to short-term learning.

PMID- 30218711
TI  - Massive Subcutaneous Emphysema Extending to the Face during Total Laparoscopic
      Hysterectomy.

PMID- 30218712
TI  - Evaluation of retinal structure in unilateral amblyopia using spectral domain
      optical coherence tomography.
AB  - PURPOSE: To investigate potential differences in the retinal nerve fiber layer
      (RNFL) thickness, macular thickness and foveal thickness between amblyopic eyes
      and normal fellow eyes on spectral domain optical coherence tomography (SD-OCT).
      METHODS: A cross-sectional study of patients >=10 years of age with unilateral
      amblyopia resulting from an anisometropic, strabismic or deprivative cause.
      Comprehensive ophthalmic examination was completed and the retinal structures of
      both eyes were measured using SD-OCT. We compared the measurements obtained
      between the amblyopic eye and the fellow normal eye in each subject. RESULTS:
      Twenty-six unilateral amblyopia patients with a mean age of 29.92 +/- 14.19 years
      old participated in the study, of which 17 (65.4%) were classified as
      anisometropic, 7 (26.9%) as strabismic, and 2 (7.7%) as deprivative. For the
      amblyopic eye and fellow normal eye, respectively, the mean RNFL thickness was
      95.87 +/- 14.56 MUm and 97.87 +/- 14.56 MUm (P = 0.628), the mean macular
      thickness was 270.87 +/- 14.43 MUm and 275.60 +/- 14.43 MUm (P = 0.251) and the
      mean foveal thickness was 250.59 +/- 27.82 MUm and 242.91 +/- 27.82 MUm (P =
      0.332). SD-OCT assessments revealed no statistically significant differences
      between both eyes. CONCLUSIONS: Using SD-OCT, there were no significant changes
      in the retinal structure of amblyopic eyes. Therefore, amblyopia does not seem to
      have a profound structural effect on the retinal nerve fiber layer, the macula,
      or the fovea.

PMID- 30218713
TI  - Lack of seasonal variation of Middle East Respiratory Syndrome Coronavirus (MERS
      CoV).

PMID- 30218714
TI  - Comparison of steroidogenic gene expression in mummichog (Fundulus heteroclitus)
      testis tissue following exposure to aromatizable or non-aromatizable androgens.
AB  - Androgens are a recognized class of endocrine disrupting compounds with the
      ability to impact reproductive status in aquatic organisms. The current study
      utilized in vitro exposure of mummichog (Fundulus heteroclitus) testis tissue to
      either the aromatizable androgen 17alpha-methyltestosterone (MT) or the non
      aromatizable androgen 5alpha-dihydrotestosterone (DHT) over the course of 24 h to
      determine if there were differential effects on steroidogenic gene expression.
      Testis tissue was exposed to androgen concentrations of 10-12 M, 10-9 M and 10-6
      M for 6, 12, 18 or 24 h, after which a suite of steroidogenic genes, including
      steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase
      (3betahsd) and cytochrome P450 17A1 (cyp17a1), were quantified using real-time
      polymerase chain reaction. Both androgens affected steroidogenic gene expression,
      with most alterations occurring at the 24-hour time point. The gene with the
      highest fold-change, and shortest interval to expression alteration, was 3betahsd
      for both androgens. Potential differences between the two model androgens were
      observed in increased expression of cyp17a1 and 11beta-hydroxysteroid
      dehydrogenase (11betahsd), which were only altered after exposure to DHT and in
      expression levels of cytochrome P450 11A1 (cyp11a1), which was upregulated by MT
      but not altered by DHT. Results from this study show both androgens interact at
      the gonadal level of the hypothalamus-pituitary-gonadal axis and may possess some
      distinct gene expression impacts. These data strengthen the current research
      initiatives of establishing in vitro test systems that allow toxic potential of
      untested chemicals to be predicted from molecular perturbations.

PMID- 30218715
TI  - Frequency and association of mitochondrial genetic variants with neurological
      disorders.
AB  - Mitochondria are small cytosolic organelles and the main source of energy
      production for the cells, especially in the brain. This organelle has its own
      genome, the mitochondrial DNA (mtDNA), and genetic variants in this molecule can
      alter the normal energy metabolism in the brain, contributing to the development
      of a wide assortment of Neurological Disorders (ND), including neurodevelopmental
      syndromes, neurodegenerative diseases and neuropsychiatric disorders. These ND
      are comprised by a heterogeneous group of syndromes and diseases that encompass
      different cognitive phenotypes and behavioral disorders, such as autism,
      Asperger's syndrome, pervasive developmental disorder, attention deficit
      hyperactivity disorder, Huntington disease, Leigh Syndrome and bipolar disorder.
      In this work we carried out a Systematic Literature Review (SLR) to identify and
      describe the mitochondrial genetic variants associated with the occurrence of ND.
      Most of genetic variants found in mtDNA were associated with Single Nucleotide
      Polimorphisms (SNPs), ~79%, with ~15% corresponding to deletions, ~3% to Copy
      Number Variations (CNVs), ~2% to insertions and another 1% included mtDNA
      replication problems and genetic rearrangements. We also found that most of the
      variants were associated with coding regions of mitochondrial proteins but were
      also found in regulatory transcripts (tRNA and rRNA) and in the D-Loop
      replication region of the mtDNA. After analysis of mtDNA deletions and CNV, none
      of them occur in the D-Loop region. This SLR shows that all transcribed mtDNA
      molecules have mutations correlated with ND. Finally, we describe that all mtDNA
      variants found were associated with deterioration of cognitive (dementia) and
      intellectual functions, learning disabilities, developmental delays, and
      personality and behavior problems.

PMID- 30218716
TI  - Characterization of the Clostridium thermocellum AdhE, NfnAB, ferredoxin and Pfor
      proteins for their ability to support high titer ethanol production in
      Thermoanaerobacterium saccharolyticum.
AB  - The thermophilic anaerobes Thermoanaerobacterium saccharolyticum and Clostridium
      thermocellum are good candidates for lignocellulosic ethanol production. T.
      saccharolyticum has been successfully engineered to produce ethanol at high titer
      (70 g/L). The maximum ethanol titer of engineered strains of C. thermocellum is
      only 25 g/L. We hypothesize that one or more of the enzymes in the ethanol
      production pathway in C. thermocellum is not adequate for ethanol production at
      high titer. In this study, we focused on the enzymes responsible for the part of
      the ethanol production pathway from pyruvate to ethanol. In T. saccharolyticum,
      we replaced all of the genes encoding proteins in this pathway with their
      homologs from C. thermocellum and examined what combination of gene replacements
      restricted ethanol titer. We found that a pathway consisting of Ct_nfnAB, Ct_fd,
      Ct_adhE and Ts_pforA was sufficient to support ethanol titer greater than 50 g/L,
      however replacement of Ts_pforA by Ct_pfor1 dramatically decreased the maximum
      ethanol titer to 14 g/L. We then demonstrated that the reason for reduced ethanol
      production is that the Ct_pfor1 is inhibited by accumulation of ethanol and NADH,
      while Ts_pforA is not.

PMID- 30218717
TI  - Hydrochlorothiazide binding to human serum albumin induces some compactness in
      the molecular structure of the protein: A multi-spectroscopic and computational
      study.
AB  - The interaction between hydrochlorothiazide (HCTZ), a diuretic drug, with human
      serum albumin (HSA) was investigated by different biophysical approaches such as
      UV absorption, circular dichroism (CD), Fourier transform infrared (FT-IR), and
      fluorescence spectroscopy in 50 mM sodium phosphate buffer, pH 7.4. The results
      of fluorescence titration experiments revealed that HCTZ strongly quenches the
      intrinsic fluorescence of HSA through a static quenching mechanism. Binding
      constants and the number of binding sites were calculated using Stern-Volmer
      plots. Thermodynamic analysis of the binding data elucidated that hydrogen
      bonding and van der Waals interactions played the major role in the binding
      process. Computation of the protein surface hydrophobicity (PSH) index using 1
      anilinonaphtalene-8-sulfonate indicated that considerable decrement in PSH value
      of the protein happened upon drug binding. The binding site of HCTZ in HSA was
      identified using warfarin and ibuprofen as site markers, a result confirmed by
      molecular docking study. The results of CD experiments showed that some
      alterations occurred in the structure of the protein upon ligation. Also, the
      results of FT-IR experiments were in good agreement with CD experiments. It looks
      like that both secondary and tertiary structures of HSA have been affected upon
      HCTZ binding.

PMID- 30218718
TI  - Quantifying beta-agonist utilization: Occasions or puffs?

PMID- 30218719
TI  - Lipopolysaccharide from Porphyromonas gingivalis promotes autophagy of human
      gingival fibroblasts through the PI3K/Akt/mTOR signaling pathway.
AB  - AIMS: Lipopolysaccharide (LPS) is a major component of cell wall in gram-negative
      bacteria and has been proved to be a predominant pathogenic factor in
      periodontitis. Porphyromonas gingivalis (P.g) was abundant in patients with
      periodontitis and was associated with patient clinic-pathological
      characteristics. Furthermore, autophagy is a potential mechanism in inflammatory
      disease. In this study, we hypothesized that LPS from P.g may affect the
      physiological functions of human gingival fibroblasts (HGFs) through activating
      cellular autophagy. However, it remains unclear what molecular basis related to
      LPS-induced autophagy in HGFs. MAIN METHODS: Here, we initially addressed the
      contribution of LPS from P.g in inducing autophagy in HGFs. Through a combination
      of morphology and quantification approaches involving autophagosomes formation
      observation as well as microtubule-associated protein light chain 3 (LC3)-II
      conversion. We further evaluated whether the PI3K/Akt/mTOR signaling could
      mediate LPS-induced autophagy in HGFs. KEY FINDINGS: Our results revealed that
      autophagy was more obvious in LPS-treated cells compared with that in control
      groups. Finally, our results demonstrated that LPS from P.g promoted autophagy in
      HGFs and was negatively regulated by PI3K/Akt/mTOR. SIGNIFICANCE: Analysis of
      these data implicates that LPS from P.g has a significant impact on the autophagy
      of HGFs by suppressing PI3K/Akt/mTOR signaling pathway.

PMID- 30218720
TI  - Aerobic exercise training prevents kidney lipid deposition in mice fed a
      cafeteria diet.
AB  - AIM: The objective of this study was to investigate the potential of aerobic
      exercise training (AET) to prevent kidney lipid accumulation and the contribution
      of renal metabolism to mediate this response. MAIN METHODS: Male C57BL/6J mice
      were assigned into groups CHOW-SED (chow diet, sedentary; n = 13), CHOW-TR (chow
      diet, trained; n = 13), CAF-SED (cafeteria diet, sedentary; n = 13) and CAF-TR
      (cafeteria diet, trained; n = 13). AET consisted in running sessions of 60 min at
      60% of maximal speed conducted five days per week for eight weeks. KEY FINDINGS:
      AET prevented weight gain in both trained groups. Food intake was not different
      among groups, however water intake, urine output, urine potassium and osmolarity
      were reduced in CAF-SED and CAF-TR groups. Kidney lipid deposition increased in
      CAF-SED (4.12 +/- 0.5%/area) compared with CHOW-SED (1.7 +/- 0.54%/area), and the
      AET prevented this increase in the CAF-TR group (2.1 +/- 0.5%/area). The Bowman's
      capsule area decreased in CAF-SED and CAF-TR groups while the Bowman' space
      reduced in CAF-SED compared to CHOW-SED group, which was prevented by AET in the
      CAF-TF group. We observed a 27% increase in the p-AMPK expression in CAF-TR
      compared to CHOW-SED group without differences in the SIRT-1, PGC1-alpha, ACC and
      p-ACC. beta-HAD activity increased in CAF-SED (43.9 +/- 4.57 nmol.min-1.ug-1) and
      CAF-TR (44.7 +/- 2.6 nmol.min-1.ug-1) groups compared to CHOW-SED (35.1 +/- 2.9
      nmol.min-1.ug-1) e CHOW-TR (36.6 +/- 2.7 nmol.min-1.ug-1). SIGNIFICANCE: AET
      prevented kidney lipid accumulation induced by cafeteria diet and this response
      was not associated with changes in the renal metabolic activity that favors lipid
      oxidation.

PMID- 30218721
TI  - Metformin ameliorates Ox-LDL-induced foam cell formation in raw264.7 cells by
      promoting ABCG-1 mediated cholesterol efflux.
AB  - AIMS: The accumulation of lipids in macrophages contributes to the development of
      atherosclerosis. Cholesterol efflux of lipid-loaded macrophages mediated by ATP
      binding cassette (ABC) cholesterol transporters, on the other hand, has been
      shown to attenuate atherosclerosis progression in patients with unknown
      mechanism. We therefore sought to test the effect of metformin that reduced
      cardiovascular risk in diabetic patients independent of its hypoglycemia effect
      on cholesterol transport in murine raw264.7 macrophages. MATERIALS AND METHODS:
      Mouse raw264.7 macrophages were loaded with Ox-LDL (50 MUg/ml) for 24 h before
      incubated with metformin (15 MUM) for 24 h. Foam cell formation was assessed by
      Oil red staining and BIODIPY fluorescent staining as well as cholesterol-ester
      quantification by commercial kit. Cholesterol uptake and expression of scavenger
      receptors were detected by flow-cytometry. Cholesterol efflux capacity was
      measured by fluorescent plate-reader and ABC transporters were detected by
      Western Blots. Cytokines were detected by ELISA in supernatants and normalized by
      cellular lysates. KEY FINDINGS: Our results showed that metformin decreased
      oxidized low-density lipoprotein (Ox-LDL)-induced cholesterol accumulation and
      foam cell formation by increasing cholesterol efflux to HDL, which was associated
      with an upregulation of ABC transporter ABCG-1. Moreover, metformin increased Ox
      LDL-impaired IL-10 secretion, an important anti-foam cell cytokine in
      atherosclerosis. SIGNIFICANCE: Our data highlighted the therapeutic potential of
      targeting macrophage cholesterol efflux with new or existing drugs for the
      possible reduction of foam cell formation in the prevention and treatment of
      diabetes-accelerated atherosclerosis.

PMID- 30218722
TI  - The impact of positive contextual factors on the association between adverse
      family experiences and obesity in a National Survey of Children.
AB  - Adverse family experiences (AFEs) are associated with childhood obesity. We
      evaluated whether certain positive contextual factors reduce the risk of obesity
      and overweight among children exposed to AFEs in a nationally representative
      sample. Using data derived from the National Survey of Children's Health 2011-12
      (N = 43,864), we calculated the distribution of positive contextual factors (very
      good/excellent maternal mental health, neighborhood and school safety, and child
      resilience) and AFEs across weight status. The AFEs composite score was modeled
      as a categorical measure (0 or >=1 AFEs). Positive contextual factors, AFEs and
      their interactions were evaluated in weighted, adjusted, multinomial logistic
      regression models predicting the odds of overweight and obesity. Children exposed
      to lack of very good/excellent maternal mental health and at least one AFE were
      at risk for overweight (OR = 1.43; 95% CI: 1.16, 1.76) and obesity (OR = 1.53;
      95% CI: 1.22, 1.93). Unsafe school or neighborhood environment and exposure to 1
      or more AFEs was. associated with overweight (OR = 1.32; 95% CI: 1.08, 1.61) and
      obesity (OR = 1.66; 95% CI: 1.34, 2.05). Lack of child resilience and exposure to
      1 or more AFEs was associated with an increased risk of obesity (OR = 1.45; 95%
      CI: 1.17, 1.90) and overweight (OR = 1.29; 95% CI: 1.06, 1.57). These odds of
      obesity and overweight all decreased when positive contextual factors were
      present. Among children exposed to AFEs, overweight and obesity risk is reduced
      with positive contextual factors. Optimizing the early childhood environment can
      impact obesity risk.

PMID- 30218723
TI  - Increasing powers to reject licences to sell alcohol: Impacts on availability,
      sales and behavioural outcomes from a novel natural experiment evaluation.
AB  - Excessive alcohol consumption leads to negative health and social impacts at
      individual and population levels. Interventions that aim to limit the density of
      alcohol retail premises (including cumulative impact policies (CIPs)) have been
      associated with decreases in alcohol-related crime and alcohol-related hospital
      admissions. We evaluated the quantitative impact of introducing a new alcohol
      licensing policy that included a comprehensive Cumulative Impact Policy (CIP)
      enforced in seven Cumulative Impact Zones (CIZs) in one English Local Authority
      in 2013. We used time series analysis to assess immediate and longer term impacts
      on licensing decisions and intermediate outcomes, including spatial and temporal
      alcohol availability, crime, alcohol-related ambulance call-outs and on-licence
      alcohol retail sales across the Local Authority and in CIZs and non-CIZs during
      the period 2008 to 2016. We found no impact on licence application rates but post
      intervention applications involved fewer trading hours. Application approvals
      declined initially but not over the longer term. Longer term, small reductions in
      units of alcohol sold in bars (-2060, 95% confidence interval (CI) = -3033, 
      1087) were observed in areas with more intensive licensing policies ('Cumulative
      Impact Zones' (CIZs)). Significant initial declines in overall crime rates (CIZs
      = -12.2%, 95% CI = -18.0%, -6.1%; non-CIZs = -8.0%, 95% CI = -14.0%, -1.6%) were
      only partially reversed by small, longer term increases. Ambulance callout rates
      did not change significantly. The intervention was partially successful but a
      more intensive and sustained implementation may be necessary for longer term
      benefits.

PMID- 30218724
TI  - The independent and joint associations of physical activity and body mass index
      with myocardial infarction: The Tromso Study.
AB  - Physical activity and overweight are associated with myocardial infarction (MI).
      However, their joint association with MI remains unclear. Our objective was to
      examine the independent and joint association between leisure-time physical
      activity (LTPA), body mass index (BMI) and MI. This prospective cohort study
      included 16,572 men and women (47.5% women) aged 20-54 years who took part in the
      second Tromso Study. At baseline in 1979-80 LTPA was assessed by questionnaire.
      Data on MI was collected and adjudicated through hospital and causes of death
      registries between 1979 and 2013. Cox proportional hazards models were used to
      examine the independent and joint associations between LTPA, BMI and MI. The
      final sample included 16,104 individuals. During a median follow up of 34 years,
      1613 incident cases of MI were recorded. Physical inactivity and elevated BMI
      were both independently associated with MI (p for trend 0.02 and <0.001). In
      joint analyses, normal weight, inactive individuals had a 20% higher risk of MI
      compared to their active counterparts (hazard ratio (HR) 1.20 (1.02-1.41)). The
      highest risk of MI was seen in obese, inactive individuals when compared to
      normal weight, active individuals (HR 3.20 (2.30-4.44)). The risk of MI increased
      with increasing BMI regardless of the activity level. HRs were lower for active
      compared to inactive individuals within the same BMI category. The findings
      suggest that LTPA and BMI are independently associated with risk of MI. LTPA
      seems to attenuate but not eliminate the risk of MI associated with excess
      bodyweight.

PMID- 30218725
TI  - Cross-sectional associations between multiple lifestyle behaviours and excellent
      well-being in Australian adults.
AB  - Research into associations between lifestyle behaviours and health has largely
      focused on morbidity, mortality and disease prevention. Greater focus is needed
      to examine relationships between lifestyle behaviours and positive health
      outcomes such as well-being. This study aims to examine the associations between
      multiple lifestyle behaviours and excellent well-being. Participants (n = 6788)
      were adults in the member database of the 10,000 Steps Australia project who were
      asked to participate in an online survey in November-December 2016. Well-being
      (WHO-5) Smoking, dietary behaviour, alcohol consumption, physical activity,
      sitting time, sleep duration, and sleep quality were assessed by self-report.
      Logistic regression analyses were used to examine relationships between excellent
      well-being (top quintile) and the individual lifestyle behaviours and also a
      lifestyle behaviour index (the number of lower-risk behaviours performed). Lower
      risk dietary behaviour (OR = 1.29, 95% CI: 1.10-1.51), physical activity (OR =
      1.90, 95% CI: 1.48-2.42), sitting time (OR = 1.46, 95% CI: 1.26-1.69), sleep
      duration (OR = 1.52, 95% CI: 1.32-1.75) and higher sleep quality (OR = 2.98, 95%
      CI: 2.55-3.48) were positively associated with excellent well-being, after
      adjusting for socio-demographics, chronic disease, depression, anxiety and all
      other lifestyle behaviours. Engaging in a higher number of lower risk lifestyle
      behaviours was positively associated with excellent well-being. These results
      highlight the need for multiple lifestyle behaviour interventions to improve and
      maintain higher well-being.

PMID- 30218726
TI  - Starch-based antimicrobial films functionalized by pomegranate peel.
AB  - In this work, pomegranate peel (PGP) as an antimicrobial agent as well as a
      reinforcing agent was utilized in developing starch-based films. Hydroxypropyl
      high-amylose starch plasticized by water and glycerol was used in this work. The
      microstructure and performance of films were investigated using scanning electron
      microscope (SEM), optical microscope (OM), X-ray diffraction (XRD), dynamic
      mechanical analyzer, tensile testing, drop impact testing and disc diffusion
      test. Results clearly demonstrated that PGP inhibited the growth of both gram
      positive (S. aureus) and gram-negative (Salmonella) bacteria. Meanwhile, PGP also
      increased Young's modulus, tensile strength and stiffness of the starch-based
      films. Both OM and SEM observations indicated reasonably good compatibility
      between starch and PGP particles. The XRD results indicated that PGP retained its
      semi-crystalline structure in the film, which can be used to explain the
      mechanism of mechanical reinforcement. Since all the components are food
      ingredients, so it is expected that the developed material can be used as an
      edible film and food grade packaging material.

PMID- 30218727
TI  - Hydrogels of agarose, and methacrylated gelatin and hyaluronic acid are more
      supportive for in vitro meniscus regeneration than three dimensional printed
      polycaprolactone scaffolds.
AB  - In this study, porcine fibrochondrocyte-seeded agarose, methacrylated gelatin
      (GelMA), methacrylated hyaluronic acid (MeHA) and GelMA-MeHA blend hydrogels, and
      3D printed PCL scaffolds were tested under dynamic compression for potential
      meniscal regeneration in vitro. Cell-carrying hydrogels produced higher levels of
      extracellular matrix (ECM) components after a 35-day incubation than the 3D
      printed PCL. Cells on GelMA exhibited strong cell adhesion (evidenced with
      intense paxillin staining) and dendritic cell morphology, and produced an order
      of magnitude higher level of collagen (p < 0.05) than other materials. On the
      other hand, cells in agarose exhibited low cell adhesion and round cell
      morphology, and produced higher levels of glycosaminoglycans (GAGs) (p < 0.05)
      than other materials. A low level of ECM production and a high level of cell
      proliferation were observed on the 3D printed PCL. Dynamic compression at 10%
      strain enhanced GAG production in agarose (p < 0.05), and collagen production in
      GelMA. These results show that hydrogels have a higher potential for meniscal
      regeneration than the 3D printed PCL, and depending on the material used,
      fibrochondrocytes could be directed to proliferate or produce cartilaginous or
      fibrocartilaginous ECM. Agarose and MeHA could be used for the regeneration of
      the inner region of meniscus, while GelMA for the outer region.

PMID- 30218728
TI  - Tapioca starch-galactomannan systems: Comparative studies of rheological and
      textural properties.
AB  - Rheological properties of tapioca starch-galactomannan mixtures at different
      concentrations (0, 0.3, 0.6 and 1.0%, w/w) of guar gum, tara gum and locust bean
      gum were investigated in visco-analysis, steady and dynamic shear and textural
      analysis. Galactomannans may influence the pasting temperature and other pasting
      parameters, the viscosity and pseudoplasticity of the blend systems increased as
      time-dependence and thixotropy decreased. This can be explained by the phase
      separation of systems where the galactomannans were placed in the continuous
      phase and the volume fraction of starch granules increased its concentration in
      the disperse phase. The addition of guar gum and tara gum could accelerate the
      formation of new structures and increase the degree of structural recovery until
      a 50% more than the starch gel pastes. The apparent viscosity (etaa) and dynamic
      moduli (G' and G") of the mixed pastes increased with the addition of
      galactomannans. Changes in textural properties were significant. The gel
      hardness, gel strength and adhesiveness of gel pastes were higher in the starch
      tara gum and starch-locust bean gum systems than in the starch-guar gum system in
      gum concentrations values of 0.3 and 0.6% w/w. Overall, addition of
      galactomannans affected the rheological and textural properties of tapioca
      starch.

PMID- 30218729
TI  - Molecular features of interaction involving hen egg white lysozyme immobilized on
      graphene oxide and the effect on activity.
AB  - Nanomaterials, such as graphene oxide (GO) are being studied to decipher their
      suitability in biomedical applications. This study investigate the effect on
      structure and function of hen egg white lysozyme (HEWL) adsorbed on GO, using
      various biophysical techniques. In spite of there being not much change in the
      structure, the catalytic activity is reduced significantly. Fluorescence
      quenching indicates complex formation. Fluorescence lifetime measurement suggests
      that GO binds at or near the active site close to Trp62 and Trp108. Heat change
      associated with HEWL-GO interaction suggests hydrogen bond along with van der
      Waals and electrostatic interactions are involved in the HEWL-GO complex.
      Molecular docking indicates binding of GO at the active site corroborating
      experimental findings. Molecular dynamics simulations indicate that the blocking
      of the active site affects the flexibility of the surrounding residues and
      contribute to the reduction of the activity. Unfolding experiments indicate that
      HEWL is more prone to thermal instability in presence of GO. Together, the
      results obtained established molecular details of HEWL-GO interaction and might
      be useful in eventual biomedical applications of GO.

PMID- 30218730
TI  - Complete mitochondrial genome of Macrosteles quadrimaculatus (Matsumura)
      (Hemiptera: Cicadellidae: Deltocephalinae) with a shared tRNA rearrangement and
      its phylogenetic implications.
AB  - Comparative studies of leafhopper mitochondrial genomes suggest that genome
      rearrangements are very rare in these insects but that nucleotide sequences are
      informative of phylogenetic relationships at various levels of divergence. A
      recent study reported that tRNA cluster trnW-trnC-trnY is rearranged to trnC-trnW
      trnY in the Aster Leafhopper, Macrosteles quadrilineatus, an economically
      important North American species. The complete mitochondrial genome of the East
      Asian species, Macrosteles quadrimaculatus, sequenced and annotated here for the
      first time, reveals that this species shares the same tRNA rearrangement,
      suggesting it is a genus-level trait. The entire mitogenome of M. quadrimaculatus
      is a circular molecule 15,734 bp in size comprising 37 genes and one control
      region, which is similar to other studied hemipteran mitogenomes. The whole
      mitogenome sequence shows heavily A + T biased nucleotide composition (77.7%) and
      moderately positive AT-skews (0.120). Except for the nad5 gene which starts with
      TTG and ends with incomplete codon T, all protein-coding genes begin with ATN
      codons and terminate with TAA. All tRNA genes have typical cloverleaf secondary
      structures, except for trnS1, in which dihydrouridine (DHU) stem is simplified to
      form a loop structure. Phylogenetic analysis based on nucleotide sequence
      datasets recovered Macrosteles as monophyletic and sister to the rest of
      Deltocephalinae.

PMID- 30218731
TI  - Gelling functional property, anti-inflammatory and antinociceptive bioactivities
      of beta-D-glucan from the edible mushroom Pholiota nameko.
AB  - A beta-D-glucan was obtained from the edible mushroom Pholiota nameko by hot
      aqueous extraction and purification. NMR and methylation analyses of the purified
      fraction (GHW-PN, 1.46% yield) indicated the presence of a (1 -> 3)-linked beta-D
      glucan, highly substituted (~27%) at O-6 by single units of beta-D-Glcp or by (1 
      > 6)-beta-D-Glcp fragments. The beta-glucan (at 0.5, 1, and 2%) showed shear
      thinning behavior and when the concentration of the solution increased, there was
      an increase in apparent viscosity. The beta-D-glucan presented gel-like behavior
      and thermal stability under a simulated pasteurization process, suggesting its
      potential as a thickening and gelling agent in products submitted to temperature
      variations. The beta-D-glucan at 0.3, 1.0 and 3.0 mg kg-1 significantly inhibited
      the inflammatory pain in 24.8, 56.9 and 82.3%, respectively, in the formalin
      induced nociception in mice. The results pointed out that the beta-D-glucan (GHW
      PN) isolated from P. nameko presents potential application for the food industry
      or for medical purposes.

PMID- 30218732
TI  - Oligoarginine mediated collagen/chitosan gel composite for cutaneous wound
      healing.
AB  - In this study, the collagen/chitosan gel composite supplemented with a cell
      penetrating peptide (CPP) (Oligoarginine, R8) was prepared. Then, the
      physicochemical properties of the new collagen/chitosan/CPPs gel obtained were
      analyzed and the related characteristics were evaluated by scanning electron
      microscopy (SEM), fourier transform infrared (FTIR), differential scanning
      calorimetry (DSC), differential thermal analyzer (DTA). Furthermore, we found
      that collagen/chitosan/CPPs gel composite was capable of inhibiting
      Staphylococcus aureus growth and had good ability to heal wounds. The mice test
      results showed that collagen/chitosan/CPPs gel had the highest healing rate,
      fastest healing speed in all the treatments. After 14 days, the group treated by
      collagen/chitosan/CPPs gel showed nearly complete wound surface healing rate of
      98 +/- 4.71%. In addition, histopathological examination suggested that
      collagen/chitosan/CPPs could promote cutaneous wound healing through enhancing
      granulation tissue formation, increasing collagen deposition and promoting
      angiogenesis in the wound tissue. Meanwhile, no significant cytotoxicity of the
      gel was observed. In conclusion, the collagen/chitosan/CPPs gel composite which
      has antibacterial activity renders a high therapeutic efficiency to heal wounds.

PMID- 30218733
TI  - Application of near infrared spectroscopy for rapid determination the
      geographical regions and polysaccharides contents of Lentinula edodes.
AB  - In this study, a calibration model based on Near-infrared spectroscopy (NIR)
      technique and chemometrics method was developed for rapid and non-destructive
      detecting the polysaccharide contents of lentinula edodes samples collected from
      different regions. The polysaccharide contents of these samples were firstly
      determined by standard phenol-sulphruic acid method. Then, NIR spectra of these
      samples were collected by using Fourier transform infrared spectrometry. Based on
      these experimental data, a random forest method was further used to distinguish
      the regions of these samples, with a classification accuracy of 96.6%. After
      that, a rapid, accurate, and quantitative model was established for predicting
      the polysaccharide contents of these samples. In the model establishing process,
      some signal pre-treatment methods were optimized, and the validation results with
      highest determination coefficient (R2) and low root mean square errors of
      prediction (RMSEP) were, 0.925 and 0.720, respectively. These results showed that
      combined NIR technique with chemometrics was an effective and green method for
      lentinula edodes quality control.

PMID- 30218734
TI  - Highly toxic Cr (VI) adsorption by (chitosan-g-PMMA)/silica bionanocomposite
      prepared via emulsifier-free emulsion polymerisation.
AB  - This work focuses on developing some composites of desirable properties mainly
      for heavy metal ion adsorption from the water bodies leading to water
      remediation. Adsorption of Cr(VI) by a novel biopolymer-based hybrid
      nanocomposite material has been synthesized via emulsifier-free emulsion
      polymerisation technique and investigated its assess as proposed use. Chitosan is
      a biocompatible, biodegradable and non-toxic material, hence this biopolymer has
      been selected in this research work. The chemical modification of the biopolymer
      chitosan has been achieved via grafting of poly(methyl methacrylate) (PMMA) and
      crosslinker silica gel was added in order to improve the mechanical strength of
      the nanocomposite in nitrogen atmosphere taking ammonium persulphate as
      initiator. The resulting composite samples were characterized by using XRD, FTIR,
      SEM and TEM. Further, the biodegradability of the samples was studied at
      different time intervals from 15 days to 6 months and the so produced
      nanocomposite exhibited good biodegradability. Adsorption of Chromium (Cr) was
      investigated by varying the contact time between the adsorbate (Cr), the
      nanocomposite, pH of the solution and the doses of the composite. The optimum
      result for chromium removal was found at pH-4 and this result showed its use
      efficiently for the treatment of wastewater containing Cr (VI).

PMID- 30218735
TI  - Antitumor potential of Pllans-II, an acidic Asp49-PLA2 from Porthidium lansbergii
      lansbergii snake venom on human cervical carcinoma HeLa cells.

PMID- 30218736
TI  - Binding of LcrV protein from Yersinia pestis to human T-cells induces apoptosis,
      which is completely blocked by specific antibodies.
AB  - The V antigen (LcrV) of the plague bacterium Yersinia pestis is a potent
      protective protein that is considered as a vaccine component for humans. LcrV
      mediates the delivery of Yop toxins into host cells and upregulates TLR2
      dependent IL-10 production. Although LcrV can interact with the receptor-bound
      human interferon-gamma (hIFN-gamma), the significance of these interactions in
      plague pathogenesis is not known. In this study, we determined the parameters of
      specific interactions of LcrV and LcrV68-326 with primary human thymocytes and
      Jurkat T-leukemia cells in the presence of receptor-bound hIFN-gamma. Although
      the C-terminal region of hIFN-gamma contains a GRRA138-141 site needed for high
      affinity binding of LcrV and LcrV68-326, in the hIFN-gamma homodimer, these
      GRRA138-141 target sites becomes accessible for targeting by LcrV or LcrV68-326
      only after immobilization of the hIFN-gamma homodimer on the hIFN-gamma receptors
      of thymocytes or Jurkat T-cells. The interaction of LcrV or LcrV68-326 with
      receptor-bound hIFN-gamma on the thymocytes or Jurkat T-cells caused apoptosis of
      both cell types, which can be completely blocked by the addition of monoclonal
      antibodies specific to the LEEL32-35 and DEEI203-206 sites of LcrV. The ability
      of LcrV to utilize hIFN-gamma is insidious and may account in part for the severe
      symptoms of plague in humans.

PMID- 30218737
TI  - A novel pH-responsive quaternary ammonium chitosan-liposome nanoparticles for
      periodontal treatment.
AB  - The aim of this study was to evaluate the antibacterial activity and
      cytocompatibility of novel pH-activated nanoparticles (NPs) in vitro and in vivo.
      The NPs were synthesized from a quaternary ammonium chitosan, i.e., N,N,N
      trimethyl chitosan, a liposome, and doxycycline (TMC-Lip-DOX NPs). The
      cytocompatibility of the NPs was evaluated. The TMC-Lip-DOX NPs achieved superb
      inhibition of free mixed bacteria and biofilm formation. They also showed
      excellent biocompatibility with human periodontal ligament fibroblasts. Animal
      experiments showed that the NPs strongly inhibited biofilm formation and
      prevented alveolar bone absorption in vivo. All the results indicate that the TMC
      Lip-DOX NPs have good potential for use in the treatment of periodontal and other
      inflammatory diseases.

PMID- 30218738
TI  - Multilayer bacterial cellulose/resole nanocomposites: Relationship between
      structural and electro-thermo-mechanical properties.
AB  - The aim of this research was to fabricate multilayer insulator nanocomposites
      using phenolic resin impregnated bacterial cellulose (BC) handsheets and
      investigate the relationships between their structural and electro-thermo
      mechanical properties. G. xylinus was incubated in a static Hestrin-Schramm
      culture at 28  degrees C for 14 days. Then, BC aqueous suspension was added to
      kraft pulp aqueous suspension. The content of BC that was added to the pulp
      suspension was as follows: 5, 10 and 15%. The disintegrated BC was turned into
      handsheets by a vacuum method. Dried handsheets were immersed in phenolic resin.
      To obtain composites, 5 immersed handsheets from each treatment were laid-up and
      hot pressed at 150  degrees C under 100 MPa pressure for 10 min. The specimens
      were characterized by means of thermogravimetric analysis (TGA), differential
      scanning calorimetry (DSC), dynamic mechanical analysis (DMA), thermal mechanical
      analysis (TMA), field-emission scanning electron microscopy (FE-SEM) techniques
      and insulating tests as dielectric loss factor and breakdown voltage. The results
      of thermal analysis showed an improvement in the thermal stability and an
      increase in the evaporation enthalpy of prepared samples with higher BC content.
      The mechanical examinations indicated that by increasing BC content in
      nanocomposites, the loss modulus and tan delta increased and the storage modulus
      of specimens decreased. The coefficient of thermal expansion (CTE) of samples
      diminished with increase of BC content. FE-SEM characterization showed different
      qualities of resin impregnation of the papers. The results of insulating tests
      confirmed that dielectric loss tangent and dielectric breakdown voltage increased
      in the specimens with higher BC content.

PMID- 30218739
TI  - Differentially expressed gene (DEG) based protein-protein interaction (PPI)
      network identifies a spectrum of gene interactome, transcriptome and correlated
      miRNA in nondisjunction Down syndrome.
AB  - Down syndrome, a genetic disorder of known attribution reveals several types of
      brain abnormalities resulting in mental retardation, inadequacy in speech and
      memory. In this study, we have presented a consolidative network approach to
      comprehend the intricacy of the associated genes of Down syndrome. In this
      analysis, the differentially expressed genes (DEG's) were identified and the
      central networks were constructed as upregulated and downregulated. Subsequently,
      GNB5, CDC42, SPTAN1, GNG2, GNAZ, PRKACB, SST, CD44, FGF2, PHLPP1, APP, and FYN
      were identified as the candidate hub genes by using topological parameters.
      Later, Fpclass a PPI tool identified WASP gene, a co-expression interacting
      partner with highest network topology. Moreover, an enhanced enrichment pathway
      namely Opioid signaling was obtained using ClueGo, depicting the roles of the hub
      genes in signaling and neuronal mechanisms. The transcriptional regulatory
      factors and the common miRNA connected to them were identified by using
      MatInspector and miRTarbase. Later, a regulatory network constructed showed that
      PLAG, T2FB, CREB, NEUR, and GATA were the most commonly connected transcriptional
      factors and hsa-miR-122-5p was the most prominent miRNA. In a nutshell, these hub
      genes and the enriched pathway could help understand at a molecular level and
      eventually used as therapeutic targets for Down syndrome.

PMID- 30218740
TI  - Immune-modulation via IgD B-cell receptor suppresses allergic skin inflammation
      in experimental contact hypersensitivity models despite of a Th2-favoured humoral
      response.
AB  - Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are common skin
      inflammatory conditions. B and T cells are strongly implicated in allergic
      contact hypersensitivity (CHS) conditions. Activation of IgD B-cell receptor
      (BCR) by anti-IgD stimulation depletes mature B cells and modulates T-helper cell
      type 1/2 (Th1/2) responses in vivo. It is not known whether these effects by anti
      IgD exacerbates or ameliorates chronic skin inflammations. This study
      investigated the effects of anti-IgD and B-cell depleting anti-CD20 antibody on
      skin inflammation in CHS murine models. Chronic CHS were induced by challenges
      with allergens trimellitic anhydride (TMA) or 2,4 dinitrochlorobenzene (DNCB).
      Mice were treated with an anti-IgD or anti-CD20 at various time-points following
      allergen challenges. This study revealed that early therapeutic treatments with
      anti-IgD at 4 h after allergen challenge significantly reduced skin inflammation
      in both TMA- and DNCB-induced CHS models (P < 0.05). In contrast, anti-CD20
      treatment exacerbated skin inflammation in DNCB-induced CHS despite of an
      extensive B cell depletion (P < 0.05). Anti-IgD treatment depleted mature
      CD19+IgD+ B cells but enhanced allergen-specific IgM and total IgE productions,
      suggesting a Th2-favoured humoral response. Anti-IgD reduced neutrophilic
      infiltrations but increases accumulation of mast cells in dermal tissues. The
      anti-inflammatory effects of anti-IgD were supported by evidence of an increase
      in the percentage of regulatory B cells and T cells. Collectively, this study
      demonstrates that immune-modulation by anti-IgD treatment suppresses Th2-mediated
      allergic skin inflammation in murine models despite a skew toward a Th2-favvoured
      humoral response and therefore may present a novel treatment for chronic human AD
      and ACD.

PMID- 30218741
TI  - The human RNASET2 protein affects the polarization pattern of human macrophages
      in vitro.
AB  - Macrophages represent key inflammatory cellular effectors of the innate immune
      response. Despite being widely acknowledged as professional phagocytes, the
      functional roles played by these cells have been progressively widened over the
      years to encompass regulation of the adaptive immune system, stimulation or
      suppression of cancer cell growth and tissue remodeling. These diverse functional
      features have led to the concept of "macrophage plasticity", i.e. the ability of
      these cells to express a wide range of phenotypes endowed with different
      functional roles. Several activation programs have been described for mammalian
      macrophages, based mainly on their differential transcriptional profiles. Based
      on established in vitro experimental conditions, many researchers currently refer
      to the M1 (or M1-like) and M2 (or M2-like) terms to describe the two extremes of
      a rather broad spectrum of polarization states that macrophages can experience in
      vivo. In light of the widely recognized opposite roles of M1-like and M2-like
      macrophages on cancer growth, and our largely incomplete knowledge of the
      cellular and molecular mechanisms underlying the establishment of the M1-like
      versus M2-like balance within a tumor mass, we report here results from in vitro
      assays pointing at the human RNASET2 gene as a potential regulator of the balance
      between M1-like/M2-like macrophage polarization. Not only do our results confirm
      previous in vivo data, thus further supporting a role for this pleiotropic
      protein in the innate immune system, but they also define RNASET2 as a new
      molecular target with potential applications for in vivo reprogramming of
      macrophage polarization, an increasingly appraised anticancer strategy.

PMID- 30218742
TI  - Epidemiology of childhood-onset type 1 diabetes in Azerbaijan: Incidence,
      clinical features, biochemistry, and HLA-DRB1 status.
AB  - AIMS: Determine the incidence and typology of diabetes in children in Azerbaijan.
      METHODS: Clinical features, C-peptide, autoantibodies (glutamic acid
      decarboxylase 65 (GAD65) and islet antigen 2 (IA-2)), and HLA-DRB1 status were
      studied in 106 subjects <18 years of age who were recently diagnosed. 104 cases
      were consecutive. Incidence was determined for Baku and Absheron regions, where
      ascertainment is estimated to be essentially 100%. RESULTS: 104 of the 106 (98%)
      were diagnosed with type 1 diabetes, one with type 2 diabetes and one with
      atypical diabetes. Type 1 diabetes incidence in Baku City and Absheron was 7.05
      per 100,000 population <15 years per year. Peak age of onset was 10 years. There
      was a slight male preponderance (male:female 1.17:1), and no temporal association
      with seasons. Almost all type 1 diabetes subjects presented with classic symptoms
      including a high incidence (58%) of diabetic ketoacidosis. 86% presented with low
      C-peptide values (<0.13 nmol/L, <0.40 ng/mL) and 74% were positive for at least
      one type 1 diabetes-related autoantibody. CONCLUSIONS: Azerbaijan has a moderate
      type 1 diabetes incidence and clinical, biochemical and genetic features similar
      to that in European populations.

PMID- 30218743
TI  - The effects of cardiovascular risk factor combined anti-platelet therapy and the
      risk of cerebrovascular events in patients with T2DM in an urban community over
      96-months follow-up: The Beijing communities diabetes study 19.
AB  - OBJECTIVE: We investigated the prognostic significance of metabolic risk scores
      and aspirin with respect to cerebrovascular events. METHODS: A total of 25
      communities of diabetic patients were enrolled in Beijing Community Diabetes
      Study (BCDS) from 2008. 3413 patients with T2DM in BCDS have complete screening
      data, including blood glucose, blood pressure, lipid profiles and anti-platelet
      therapy, which were assigned metabolic score (MS) and add up to the total
      metabolic score (TMS). According to the total metabolic score (TMS), the patients
      were divided into four equal groups: Group 1 (24 < TMS < 40), Group 2 (40 < TMS <
      47), Group 3 (47 < TMS < 55) and Group 4 (55 < TMS < 87). After 96 months,
      patients were followed-up to assess the long-term effects of the multifactorial
      interventions. RESULTS: During 96-months follow-up, a total of 91 cerebrovascular
      events occurred, including acute cerebral infarction, acute cerebral hemorrhage
      and transient ischemic attack (TIA). The incidence of cerebrovascular events was
      higher in the Group 4 than in the Group 1. In Cox multivariate analyses, there
      are significant differences in incidences of cerebral infarction events among the
      four groups during the 96-months follow-up. Cox proportional hazards analysis
      revealed that, HbA1c (p <= 0.001), systolic pressure (p <= 0.001), aspirin free
      treatment (P = 0.0023) are independent predictor for cerebrovascular events in
      diabetic patients. CONCLUSIONS: This study indicates that total metabolic score
      (TMS) influences the incidence of cerebrovascular events in diabetic patients. In
      addition to good control of blood glucose, blood pressure and lipid profiles,
      anti-platelet therapy is important for the prevention of cerebrovascular events
      in T2DM. TRIAL REGISTRATION: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

PMID- 30218744
TI  - Impact of diabetes education and self-management on the quality of care for
      people with type 1 diabetes mellitus in the Middle East (the International
      Diabetes Mellitus Practices Study, IDMPS).
AB  - AIMS: Self-management (self-monitoring of blood glucose, plus self-adjustment of
      insulin dose) is important in diabetes care, but its complexity presents a
      barrier to wider implementation, which hinders attainment and maintenance of
      glycemic targets. More evidence on self-management is needed to increase its
      implementation and improve metabolic outcomes. METHODS: Data from 1316
      participants with type 1 diabetes mellitus who were enrolled from Middle East
      countries into the International Diabetes Management Practices Study (IDMPS), a
      multinational observational survey, were analyzed to assess the impact of
      education on disease management and outcomes. RESULTS: A majority (78%) of
      participants failed to achieve glycemic target (HbA1c < 7.0% [<53 mmol/mol]).
      Participants who had received diabetes education (59%) were more likely to
      practice self-management than those who had not (odds ratio [OR]: 2.51; 95%
      confidence interval [CI]: 1.7-3.69; p < 0.001), and those who practiced self
      management were more likely to attain target HbA1c than those who did not (OR:
      1.49; 95% CI: 1.06-2.09; p = 0.023). CONCLUSIONS: These relationships between
      diabetes education, self-management and glycemic control suggest that diabetes
      education provides knowledge and skills to optimize self-management, favoring
      HbA1c target attainment. Middle East health authorities should search for ways to
      facilitate access to diabetes education to optimize treatment outcomes.

PMID- 30218745
TI  - Expression, purification, and characterisation of human soluble Epoxide Hydrolase
      (hsEH) and of its functional C-terminal domain.
AB  - The human soluble Epoxide Hydrolase (hsEH) is an enzyme involved in the
      hydrolysis of endogenous anti-inflammatory and cardio-protective signalling
      mediators known as epoxyeicosatrienoic acids (EETs). EETs' conversion into the
      corresponding diols by hsEH generates non-bioactive molecules, thereby the enzyme
      inhibition would be expected to enhance the EETs bioavailability, and their
      beneficial properties. Numerous inhibitors have been developed to target the
      enzyme, some of which are showing promising antihypertensive and anti
      inflammatory properties in vivo. Thus far, the preparation of the recombinant
      enzyme for enzymatic and structural in vitro studies has been performed mainly
      using a baculovirus expression system. More recently, it was reported that the
      enzyme could be exogenously expressed and isolated from E. coli, although limited
      amounts of active protein were obtained. We herein describe two novel methods to
      yield pure recombinant enzyme. The first describes the expression and
      purification of the full-length enzyme from eukaryotic cells HEK293-F, whilst the
      second concerns the C-terminal domain of hsEH obtained from the cost-effective
      and rapid E. coli prokaryotic system. The two methods successfully generated
      satisfactory amounts of functional enzyme, with virtually identical enzymatic
      activity. Overall, the protocols described in this paper can be employed for the
      recombinant expression and purification of active hsEH, to be used in future
      biomedical investigations and for high-throughput screening of inhibitors for
      potential use in the treatment of cardiovascular disease.

PMID- 30218746
TI  - Perception of inappropriate cardiopulmonary resuscitation by clinicians working
      in emergency departments and ambulance services: The REAPPROPRIATE international,
      multi-centre, cross sectional survey.
AB  - INTRODUCTION: Cardiopulmonary resuscitation (CPR) is often started irrespective
      of comorbidity or cause of arrest. We aimed to determine the prevalence of
      perception of inappropriate CPR of the last cardiac arrest encountered by
      clinicians working in emergency departments and out-of-hospital, factors
      associated with perception, and its relation to patient outcome. METHODS: A cross
      sectional survey was conducted in 288 centres in 24 countries. Factors associated
      with perception of CPR and outcome were analyzed by Cochran-Mantel-Haenszel tests
      and conditional logistic models. RESULTS: Of the 4018 participating clinicians,
      3150 (78.4%) perceived their last CPR attempt as appropriate, 548 (13.6%) were
      uncertain about its appropriateness and 320 (8.0%) perceived inappropriateness;
      survival to hospital discharge was 370/2412 (15.3%), 8/481 (1.7%) and 8/294
      (2.7%) respectively. After adjusting for country, team and clinician's
      characteristics, the prevalence of perception of inappropriate CPR was higher for
      a non-shockable initial rhythm (OR 3.76 [2.13-6.64]; P < .0001), a non-witnessed
      arrest (2.68 [1.89-3.79]; P < .0001), in older patients (2.94 [2.18-3.96]; P <
      .0001, for patients >79 years) and in case of a "poor" first physical impression
      of the patient (3.45 [2.36-5.05]; P < .0001). In accordance, non-shockable and
      non-witnessed arrests were both associated with lower survival to hospital
      discharge (0.33 [0.26-0.41]; P < 0.0001 and 0.25 [0.15-0.41]; P < 0.0001,
      respectively), as were older patient age (0.25 [0.14-0.44]; P < 0.0001 for
      patients >79 years) and a "poor" first physical impression (0.26 [0.19-0.35]; P <
      0.0001). CONCLUSIONS: The perception of inappropriate CPR increased when
      objective indicators of poor prognosis were present and was associated with a low
      survival to hospital discharge. Factoring clinical judgment into the decision to
      (not) attempt CPR may reduce harm inflicted by excessive resuscitation attempts.

PMID- 30218747
TI  - Targeting apoptosis by 1,2-diazole through regulation of EGFR, Bcl-2 and CDK-2
      mediated signaling pathway in human non-small cell lung carcinoma A549 cells.
AB  - Lung cancer is the leading cause of cancer deaths worldwide and non-small cell
      lung carcinoma (NSCLC), a heterogeneous class of tumors, represents approximately
      85% of all new lung cancer diagnosis. Conventional treatment options have limited
      efficacy because most cases are in the advanced stage at the time of diagnosis.
      The present study evaluates the anti-cancer activity of 1,2-diazole (pyrazole), a
      natural compound from mangrove plant Rhizophora apiculata (R.apiculata) on A549
      lung carcinoma cells. In the present study the anti-cancer mechanism of pyrazole,
      was examined by the expression level of proteins Epidermal growth factor receptor
      (EGFR), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) and Cyclin
      dependent kinase-2 (CDK-2) which are commonly associated with the cell signaling
      pathways that control cell survival and apoptosis, that could facilitate to
      develop a novel target and effective treatment approach for patients with NSCLC.
      Pyrazole significantly induced cell cycle arrest and initiated apoptosis through
      inhibition of downstream components of EGFR tyrosine kinase pathway. Pyrazole
      disrupts the mitochondrial membrane potential and modulated the protein levels of
      Bax and Bcl-2 which could probably lead to caspase-3 activation. Furthermore,
      Pyrazole suppresses the expression of CDK-2 resulting in cell cycle arrest at G1
      phase and in the G1-S phase transition. Taken together, the current study
      provides new insight in to the precise molecular mechanisms responsible for the
      anti-cancer activity of pyrazole in NSCLC, A549 cells. The study opens an avenue
      for development of a natural compound as a potential therapeutic agent which
      could target cell signaling pathways to combat human NSCLC.

PMID- 30218748
TI  - 5-HTT, BMPR2, EDN1, ENG, KCNA5 gene polymorphisms and susceptibility to pulmonary
      arterial hypertension: A meta-analysis.
AB  - BACKGROUND: The influence of 5-HTT, BMPR2, EDN1, ENG, KCNA5 genes polymorphisms
      on susceptibility of pulmonary arterial hypertension remains uncertain. This meta
      analysis is conducted for further study. METHODS: We conducted a literature
      search on PubMed and ISI web of science databases for searching relevant articles
      until November 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CIs)
      were calculated. A total of 17 articles with 2631 PAH subjects and 5139 controls
      were included in the final meta-analysis. Statistical software Stata13.0 was used
      for data-analysis. RESULTS: A significant relationship was found between the 5
      HTT L/S polymorphism and PAH in all the genetic models [LL vs. SS: OR = 1.60, 95%
      CI, 1.11-2.32; LS vs. SS: OR = 1.55, 95% CI, 1.10-2.21; (LS + LL) vs. SS: OR =
      1.56, 95% CI, 1.13-2.17; L vs. S: OR = 1.32, 95% CI, 1.08-1.62]. There were also
      associations of the SERT L/S polymorphism with IPAH and PAH in COPD [IPAH L/S: OR
      = 1.26, 95% CI, 1.01-1.57; PAH in COPD L/S: OR = 1.42, 95% CI, 1.04-1.94]. In
      addition, the results showed a statistically significant association between EDN1
      rs5370 polymorphism and the risk of PAH in all the genetic models [TT vs. GG: OR
      = 3.32, 95% CI, 1.30-8.51; TG vs. GG: OR = 2.68, 95% CI, 1.54-4.66; (TG + TT) vs.
      GG: OR = 2.82, 95% CI, 1.69-4.71; T vs. G: OR = 2.43, 95% CI, 1.60-3.68].
      However, the significant association was not found between BMPR2 rs1061157, KCNA5
      rs10744676, ENG rs3739817 polymorphisms and the risk of PAH (all p > 0.05).
      CONCLUSIONS: 5-HTT L/S polymorphism and END1 rs5370 polymorphism were correlated
      with significantly increased risk of PAH. Moreover, L allele in 5-HTT gene
      increased susceptibility to IPAH and PAH in COPD.

PMID- 30218749
TI  - A comparative study on the effects of acute and chronic downhill running vs
      uphill running exercise on the RNA levels of the skeletal muscles PGC1-alpha,
      FNDC5 and the adipose UCP1 in BALB/c mice.
AB  - The purpose of this study was to investigate the effect of a single bout and 8
      weeks of downhill running versus uphill running exercise on expression of PGC1
      alpha, FNDC5 and UCP1 in mice. Forty-eight BALB/c male mice weighing 25-30 g were
      randomly assigned into 8 groups: 1) acute downhill running (ADR) on a -15 degrees
      slope; 2) acute uphill running (AUR) on a +15 degrees  slope; 3) acute running
      without inclination (AWI), 4) acute without exercise as control (ACtrl), 5)
      chronic downhill running (CDR) on a -15 degrees  slope; 6) chronic uphill running
      (CUR) on a +15 degrees slope; 7) chronic running without inclination (CWI), 8)
      chronic without exercise as control (CCtrl). Twenty four hours after the last
      training session, the mice were sacrificed and Calf muscles (including soleus and
      gastrocnemius) and quadriceps muscles (including Rectus femoris and vastus
      intermedius) were obtained and expression levels of PGC1-alpha and FNDC5 in crus
      and quadriceps muscles and UCP1 in visceral and subcutaneous adipose tissues were
      measured and compared between the groups. PGC-1alpha and FNDC5 mRNA levels
      increased after treadmill exercise training in all acute and chronic exercise
      groups in both skeletal muscle groups. Furthermore mRNA level of UCP1 in
      subcutaneous adipose tissue but not in visceral adipose tissue increased both
      after acute and chronic exercise. Collectively, data showed that downhill running
      exercise to be more effective than other exercises, as downhill running has led
      to a greater improvement in metabolism may be considered more effective for
      browning of fat tissue.

PMID- 30218750
TI  - Vitamin D binding protein polymorphisms influence susceptibility to hepatitis C
      virus infection in a high-risk Chinese population.
AB  - Vitamin D binding protein (VDBP) plays an important role in the immune modulation
      and pathogenesis of hepatitis C viral (HCV) infection by influencing serum
      vitamin D levels. The present study aims to evaluate the association of VDBP
      genetic polymorphisms with susceptibility to and chronicity of HCV infection in a
      high-risk Chinese population. Seven genetic variants in the VDBP gene were
      genotyped in a case-control study of 886 patients with HCV persistent infection,
      539 subjects with spontaneous clearance, and 1081 uninfected controls. Logistic
      regression analysis was used to assess the effects of these variants on HCV
      infection outcomes. The results showed that two variants rs7041-G and rs3733359-T
      alleles were significantly associated with increased susceptibility of HCV
      infection, and the combined effect of the two unfavorable alleles was related to
      an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 8.16 * 10
      4). Interaction analysis manifested that rs7041-GT/GG and rs3733359-CT/TT jointly
      increased risk of HCV infection. Moreover, haplotype analysis suggested that
      compared with the most frequent TC haplotype, the haplotype carrying GT indicated
      a risk effect of HCV infection [odds ratio (OR) = 1.464]. However, no significant
      associations were observed for the other five variants. These findings implied
      that VDBP rs7041-G and rs3733359-T variants may contribute to increased
      susceptibility to HCV infection in a high-risk Chinese population.

PMID- 30218751
TI  - MAN1B1 is associated with poor prognosis and modulates proliferation and
      apoptosis in bladder cancer.
AB  - Bladder cancer (BC) has been regarded as the most common malignancy of the
      urinary system worldwide. With lack of investigations for molecular pathogenesis
      underlying that develop BC, the therapeutic efficacy of several therapeutic
      approaches existing is still unsatisfactory. Here, our study aimed to explore the
      potentially biological function of MAN1B1 on BC. In this study, MAN1B1 expression
      level in BC tissues and normal tissues was analyzed based on The Cancer Genome
      Atlas (TCGA) data and correlation between its expression and prognosis was
      determined using Kaplan-Meier analysis. Knockout of MAN1B1 was performed using
      silencing RNA and the efficacy of MAN1B1 knockout was identified using
      quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis.
      The BC cells proliferation was assessed by Cell Counting Kit-8 (CCK8) assay, and
      then the cells apoptosis was detected by Annexin V-fluorescein isothiocyanate
      (Annexin V-FITC)/propidium iodide (PI) staining and flow cytometry following
      MAN1B1 knocked down by small interfering RNA. Protein kinase B (AKT) signaling
      was evaluated by detecting related markers, namely AKT, p-AKT, 4E-BP-1 and Bax
      using western blot assay. As a result, the MAN1B1 expression was higher in BC
      tissues than those in normal tissues, besides, its overexpression was associated
      with poor prognosis. Moreover, MAN1B1 reduction by silencing RNA approach
      resulted in BC cells proliferation suppression and BC cells apoptosis promotion.
      Finally, AKT signaling activity was inhibited by MAN1B1 silencing. Taken
      together, these results unraveled that MAN1B1 may act on an oncogenic action in
      BC, which improved the likelihood of MAN1B1 taking on a promising prognostic
      biomarker and a potential target for treating BC.

PMID- 30218752
TI  - Investigation of gene evolution in vertebrate genome reveals novel insights into
      spine study.
AB  - Vertebrate genomes have been considered to have undergone a complicated evolution
      during their early period and to have generated a large number of genetic
      templates with novel functions, such as an extended spinal cord and a dorsal
      central nervous system. However, consistent gene evolution in vertebrate genomes
      has not been fully elucidated. In this study, we have systematically investigated
      the gene evolution in vertebrates utilizing a series of comparative genomics
      tools. We determined that three critical genes were consistently lost in
      vertebrate genomes, and 14 genes initially emerged in vertebrate formation.
      Furthermore, another 29 genes were identified with consistent amino acid
      variation between the vertebrates and invertebrates. A function analysis of five
      genes (TEP3, ABLIM2, ABLIM3, GAD1 and GAD2) was performed, and their evolution
      mechanisms in vertebrate genomes further investigated. These findings provide
      novel insights for studying the vertebrate evolution and spine development.

PMID- 30218753
TI  - Aberrant differential expression of EZH2 and H3K27me3 in extranodal NK/T-cell
      lymphoma, nasal type is associated with disease progression and prognosis.
AB  - Enhancer of zeste homolog 2 (EZH2), a H3K27-specific histone methyltransferase,
      has been shown to be frequently overexpressed in various human cancers including
      lymphoma. Here we investigate the expression and functionality of EZH2 and
      H3K27me3 in extranodal NK/T-cell lymphoma, nasal type (ENKTL). Results of
      NanoString analysis revealed that EZH2 and related histone H3 families were
      upregulated genes in ENKTL tissues. Results of immunohistochemistry (IHC)
      demonstrated that EZH2 and trimethylation of Lys-27 in histone (H3K27me3) were
      highly expressed in 55.2% and 78.0% of patients with ENKTL, respectively. EZH2
      overexpression was significantly associated with higher tumor cell proliferation
      (r=0.582, P=.000), advanced stage (P=.012), and predicted poorer overall survival
      (OS) (P=.016) in ENKTL. H3K27me3-positive expression was correlated with lower
      tumor cell proliferation (r=-0.623, P=.036), earlier stage (P=.043), and
      predicted better OS (P=.020). In addition, EZH2 and H3K27me3 showed inverse
      correlations (r=-0.652, P=.002) in clinical samples by IHC. Further, inhibition
      of EZH2 by 3-deazaneplanocin A (DZNep) significantly suppressed tumor cell
      growth. Interestingly, pharmacological suppression of JAK3/STAT3 pathway
      effectively reduced EZH2 and enhanced H3K27me3 in NK/T tumor cells lines. Our
      data suggest that EZH2 and H3K27me3 are important prognostic markers and
      potential therapeutic targets in ENKTL.

PMID- 30218754
TI  - Study of the revisited, revised, and expanded Silva pattern system for Chinese
      Endocervical adenocarcinoma patients.
AB  - As a new pattern-based classification, the Silva pattern system has been recently
      developed to evaluate invasive lymph node (LN) metastasis and the prognosis of
      endocervical adenocarcinoma (EAC). Therefore, our study was conducted to explore
      the reproducibility and prognostic significance of this system in a multi
      institutional Chinese cohort, with the goal of revising and expanding its
      application. The clinicopathological data of 191 EAC patients from 3 medical
      centers were examined in a retrospective manner. The Silva pattern system
      demonstrated great prognostic value, significance in guiding treatment selection,
      and acceptable reproducibility in 191 patients that included additional
      histologic variants and 124 usual-type EAC patients. Collectively, compared with
      usual-type EAC, the whole cohort demonstrated similar statistical significance
      for relevant clinicopathologic parameters, such as FIGO stage (R=0.612 vs.
      R=0.600), tumor thickness (P<.0001 vs. P<.0001), lymphovascular invasion (P<.0001
      vs. P<.0001), LN metastasis (P=.033 vs. P=.018), perineural invasion (P=.003 vs.
      P=.001) and recurrence-free survival (P=.047 vs. P=.020). Moreover, perineural
      invasion was significantly correlated (P=.001) with the Silva pattern system and
      appeared in most Silva C tumors. In conclusion, the Silva pattern system is
      consistent with the biological behavior of EAC and has acceptable
      reproducibility. Compared with FIGO stage, it can predict patient prognosis
      before surgery. We suggest revising the Silva C criteria by adding perineural
      invasion as a factor and propose expanding the Silva pattern system to include
      more histologic variants. It appears that the Silva pattern system can be applied
      in routine clinical practice to guide EAC therapeutic strategies in the near
      future.

PMID- 30218755
TI  - Overexpression of ADAMTS-2 in tumor cells and stroma is predictive of poor
      clinical prognosis in gastric cancer.
AB  - ADAMTS-2 is a member of the ADAMTS family and is a procollagen N-proteinase. The
      objective of our research is to explore the prognostic significance of ADAMTS-2
      in gastric carcinoma. A total of 655 samples with full clinicopathological data
      were investigated in this study. Tissue microarray immunohistochemistry (TMA-IHC)
      analysis was used to analyze the relationship between clinicopathological
      characteristics and ADAMTS-2 expression. Oncomine and Kaplan-Meier plotters were
      performed for the relationship analysis between prognosis and ADAMTS-2 expression
      in patients with gastric cancer (GC). Compared with that of normal tissues, the
      ADAMTS-2 protein expression was remarkably higher in gastric cancer cells and
      fibroblast cells. The results of univariate analysis indicated that the
      expression of ADAMTS-2 in tumor cells and fibroblast cells, Lauren
      classification, TNM grade, and carcinoembryonic antigen (CEA) level in gastric
      cancer were all correlated with the overall survival. The results of multivariate
      analysis indicated that the high expression of ADAMTS-2 in gastric cancer cells
      and fibroblast cells both were independent prognostic factors. Therefore, ADAMTS
      2 may be a potential biomarker for assessing the prognosis of gastric carcinoma.

PMID- 30218756
TI  - Usefulness of complementary next-generation sequencing and quantitative
      immunohistochemistry panels for predicting brain metastases and selecting a
      treatment outcomes of non-small cell lung cancer.
AB  - To demonstrate the usefulness of complementary next-generation sequencing (NGS)
      and immunohistochemistry (IHC) counting, we analyzed 196 patients with non-small
      cell lung cancer (NSCLC) who underwent surgical resection and adjuvant
      chemotherapy. Formalin-fixed paraffin-embedded samples of adenocarcinoma (ADC),
      squamous cell carcinoma (SqCC), and large-cell carcinoma (LCC) were used to
      prepare tissue microarrays and were examined by protein H-score IHC image
      analysis and NGS for oncogenes and proto-oncogenes and genes of tumor
      suppressors, immune checkpoints, epithelial-mesenchymal transition factors,
      tyrosine kinase receptors, and vascular endothelial growth factors (VEGFs). In
      patients with brain metastases, primary tumors expressed lower PIK3CA protein
      levels. Overexpression of TP53 and a higher PD-L1 protein H-score were detected
      in patients that underwent surgical treatment followed by chemotherapy as
      compared to those that underwent only surgical treatment The absence of brain
      metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4,
      and ZEB1. The combination of protein overexpression according to IHC and mutation
      according to NGS was rare (i.e., represented by a very low percentage of
      concordant cases), except for TP53 and VEGF. Our data suggest that protein levels
      detected by IHC may be a useful complementary tool when mutations are not
      detected by NGS and also support the idea to expand this approach beyond ADC to
      include SqCC and even LCC, particularly for patients with unusual clinical
      characteristics. Conversely, well-pronounced immunogenotypic features appeared to
      predict the clinical outcome after univariate and multivariate analyses. Patients
      with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1
      complemented with PD-L1 or TP53 protein lower expression that only underwent
      surgical treatment, who develop brain metastases, may have the worst prognosis.

PMID- 30218757
TI  - Accelerated accumulation of retinal alpha-synuclein (pSer129) and tau,
      neuroinflammation, and autophagic dysregulation in a seeded mouse model of
      Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      accumulation of misfolded alpha-synuclein within the central nervous system
      (CNS). Visual problems in PD patients are common, although retinal pathology
      associated with PD is not well understood. The purpose of this study was to
      investigate retinal pathology in a transgenic mouse model (TgM83) expressing the
      human A53T alpha-synuclein mutation and assess the effect of alpha-synuclein
      "seeding" on the development of retinal pathology. Two-month-old TgM83 mice were
      intracerebrally inoculated with brain homogenate from old (12-18 months) TgM83
      mice. Retinas were then analyzed at 5 months of age. We analyzed retinas from 5
      month-old and 8-month-old uninoculated healthy TgM83 mice, and old (12-18 months)
      mice that were euthanized following the development of clinical signs. Retinas of
      B6C3H mice (genetic background of the TgM83 mouse) served as control. We used
      immunohistochemistry and western blot analysis to detect accumulation of alpha
      synuclein, pTauThr231, inflammation, changes in macroautophagy, and cell death.
      Raman spectroscopy was used to test the potential to differentiate between
      retinal tissues of healthy mice and diseased mice. This work demonstrates retinal
      changes associated with the A53T mutation. Retinas of non-inoculated TgM83 mice
      had accumulation of alpha-synuclein, "pre-tangle" tau, activation of retinal
      glial cells, and photoreceptor cell loss by 8 months of age. The development of
      these changes is accelerated by inoculation with brain homogenate from clinically
      ill TgM83 mice. Compared to non-inoculated 5-month-old TgM83 mice, retinas of
      inoculated 5-month-old mice had increased accumulation of alpha-synuclein
      (pSer129) and pTauThr231 proteins, upregulated microglial activation, and
      dysregulated macroautophagy. Raman spectroscopic analysis was able to
      discriminate between healthy and diseased mice. This study describes retinal
      pathology resulting from the A53T mutation. We show that seeding with brain
      homogenates from old TgM83 mice accelerates retinal pathology. We demonstrate
      that Raman spectroscopy can be used to accurately identify a diseased retina
      based on its biochemical profile, and that alpha-synuclein accumulation may
      contribute to accumulation of pTauThr231 proteins, neuroinflammation, metabolic
      dysregulation, and photoreceptor cell death. Our work provides insight into
      retinal changes associated with Parkinson's disease, and may contribute to a
      better understanding of visual symptoms experienced by patients.

PMID- 30218758
TI  - Post-stroke administration of omega-3 polyunsaturated fatty acids promotes
      neurovascular restoration after ischemic stroke in mice: Efficacy declines with
      aging.
AB  - Post-stroke treatment with omega-3 polyunsaturated fatty acids (n-3 PUFAs) may be
      a promising therapy in young animals but this has not been tested in aged
      subjects, a population at most risk of ischemic stroke. Herein we examined the
      therapeutic efficacy of n-3 PUFAs after distal middle cerebral artery occlusion
      (dMCAO) in young (10-12 weeks old) and aged (18 months old) mice. Post-ischemic
      mice were randomly assigned to 4 groups that received: 1) regular food with low
      content of n-3 PUFAs, 2) intraperitoneal docosahexaenoic acid (DHA, a major
      component of n-3 PUFAs) injections, 3) Fish oil (FO, containing high
      concentration of n-3 PUFAs) dietary supplement, or 4) combined treatment with DHA
      and FO dietary supplement. Long-term neurorestoration induced by n-3 PUFA post
      stroke administration and its underlying mechanism(s) were analyzed up to 35 days
      after dMCAO. Aged mice showed more severe neurological deficits than young mice
      after dMCAO with histological lesions extended to the striatum. Notably, post
      stroke treatment with combined DHA injections and FO dietary supplementation was
      more effective in reducing brain injury and improving sensorimotor function in
      aged mice than either treatment alone, albeit to a lesser extent than in the
      young mice. Unlike the improvement in spatial cognitive function observed in
      young mice, the combined treatment regimen failed to improve cognitive function
      in aged mice. The reduction in stroke-induced neurological deficits with n-3 PUFA
      post-treatment was associated with enhanced angiogenesis, oligodendrogenesis,
      neuron survival and white matter restoration. Together, these results indicate
      that the neurological benefits of n-3 PUFA administration after stroke extend to
      older animals and are associated with improved neuronal survival and brain
      remodeling, therefore suggesting that post-stroke administration of n-3 PUFAs is
      a viable clinically relevant treatment option against stroke.

PMID- 30218759
TI  - Mitochondria and neuroprotection in stroke: Cationic arginine-rich peptides
      (CARPs) as a novel class of mitochondria-targeted neuroprotective therapeutics.
AB  - Stroke is the second leading cause of death globally and represents a major cause
      of devastating long-term disability. Despite sustained efforts to develop
      clinically effective neuroprotective therapies, presently there is no clinically
      available neuroprotective agent for stroke. As a central mediator of
      neurodamaging events in stroke, mitochondria are recognised as a critical
      neuroprotective target, and as such, provide a focus for developing mitochondrial
      targeted therapeutics. In recent years, cationic arginine-rich peptides (CARPs)
      have been identified as a novel class of neuroprotective agent with several
      demonstrated mechanisms of action, including their ability to target mitochondria
      and exert positive effects on the organelle. This review provides an overview on
      neuronal mitochondrial dysfunction in ischaemic stroke pathophysiology and
      highlights the potential beneficial effects of CARPs on mitochondria in the
      ischaemic brain following stroke.

PMID- 30218760
TI  - Histologic Validation of 11Carbon-Acetate Positron Emission Tomography/Computer
      Tomography in Detecting Lymph Node Metastases in Prostate Cancer.
AB  - PURPOSE: Conventional imaging cannot definitively detect nodal metastases from
      prostate cancer (PCa). We histologically validated 11-carbon-Acetate (11C
      Acetate) PET/CT for identifying nodal metastases, examining PCa factors that
      influence detection rates. MATERIALS AND METHODS: Patients with 11C-Acetate-avid
      PET/CT imaged pelvic/retroperitoneal lymph nodes underwent high-extended robotic
      lymphadenectomy. A standardized mapping-template, comprising 8 pre-determined
      anatomic regions, was dissected during lymphadenectomy, allowing matched, region
      based analysis and comparison of imaging and histological data. RESULTS: In 25
      patients, a total of 2149 lymph nodes were excised (mean 86 nodes/patient; range
      27-136), with 528 (22%) harboring metastases (mean 21 positive-nodes/patient;
      range 0-109). In total, 174 anatomical regions had matching imaging-histologic
      data. 11C-Acetate PET/CT accurately identified 48 node-positive regions and
      accurately ruled-out 88 regions as metastasis-free. 11C-Acetate sensitivity,
      specificity, PPV and NPV were 67%, 84%, 74% and 79%, respectively. Increasing
      histologically-measured metastatic-lesion size in long-axis diameter (LAD)
      (<=5mm, 6-10mm, 11-15mm, 16-20mm, >=21mm), respectively, correlated with improved
      11C-Acetate detection rates (45%, 62%, 81%, 89%, 100%). Each standard uptake
      value (SUV) unit increase correlated with 1.9 mm increase in nodal LAD (p<0.001)
      and 1.2 mm in short-axis diameter (SAD) (p<0.001). Positive 11C-Acetate PET/CT
      imaging correlated with histologic lymph node size (LAD 12mm, SAD 6mm),
      metastatic-lesion size (LAD 11mm, SAD 6mm) and extra-nodal extension (true
      positive 88% vs false-negative 58%; p=0.005). CONCLUSION: 11C-Acetate PET/CT
      imaging can identify PCa metastatic nodal disease. However, it under-estimates
      true cephalad extent of nodal involvement, performing better in pelvis than
      retroperitoneum. SUV, histological nodal size, intra-nodal metastasis size, and
      extra-nodal extension correlate with cancer-bearing nodes.

PMID- 30218761
TI  - Minority recruitment trends in phase III prostate cancer clinical trials (2003
      2014): progress and critical areas for improvement.
AB  - PURPOSE: U.S. minority groups have been historically underrepresented in phase
      III prostate cancer clinical trials despite often having higher risk disease.
      This study analyzes enrollment trends of major U.S. racial/ethnic groups in phase
      III prostate cancer trials between 2003-2014 compared to Surveillance,
      Epidemiology, and End Results (SEER) incidence data. MATERIALS AND METHODS: Phase
      III prostate cancer trials primarily enrolling patients from the U.S. were
      identified in the ClinicalTrials.gov database. Enrollment trends were analyzed
      for major racial/ethnic groups. Prostate cancer incidence data from the SEER
      registry was used to identify enrollment targets. The enrollment difference was
      determined by calculating the absolute difference between the percentage of a
      racial/ethnic subgroup in the SEER registry population and the percentage of that
      subgroup in the phase III prostate cancer trial population. RESULTS: Among 39
      studies identified, African American enrollment in therapeutic trials increased
      across the study period (p<0.001). The enrollment difference for African
      Americans was -9.0% (95% CI, -7.6 to -10.5; p<0.001) in 2003-05 and 1.4% (95% CI,
      0.2 to 2.6; p = 0.020) in 2012-14. However, African American men were under
      enrolled in metastatic disease trials (enrollment difference = -5.8%; 95% CI, 
      4.8 to -6.8; p<0.001). Latino and Asian American men were consistently under
      enrolled in all trial types. CONCLUSIONS: U.S. minority groups were largely under
      enrolled in phase III prostate cancer trials between 2003-2014. While recruitment
      efforts may have had an impact, as demonstrated by increased enrollment of
      African American men, there remains a need to expand recruitment efforts to
      achieve diversity in trials.

PMID- 30218762
TI  - Outpatient robotic unilateral extravesical ureteral reimplantation in the
      pediatric population: short-term assessment of safety.
AB  - PURPOSE: Robotic extravesical ureteral reimplantation has been established as a
      viable option for surgical management of vesicoureteral reflux. Typically, this
      procedure is associated with a hospital stay for routine postoperative care. The
      aim of the study was to assess the short-term safety of robotic unilateral
      extravesical ureteral reimplantation as a scheduled outpatient procedure in a
      pediatric population. MATERIAL AND METHODS: A retrospective cohort study was
      performed for patients who underwent robotic extravesical ureteral reimplantation
      between June 2012 and January 2018. No regional blocks were performed. Patients
      were discharged from the post anesthesia care unit without an extended stay, as a
      scheduled outpatient procedure. Postoperative outcomes included 30-day Emergency
      Room (ER) visits, readmissions, and Clavien-Dindo (CD) grade I-V complications.
      RESULTS: A total of 27 patients were identified (4 males, 23 females). Median age
      was 85 months (range 27-210). Median weight was 26 kilograms (range 13-97).
      Median robotic console time was 140 minutes (range 84-257). No patients required
      a hospital stay for pain management. Two (9%) patients required unplanned
      antibiotic therapy postoperatively (CD grade II) for management of bacterial
      cystitis and pneumonia. The patient with pneumonia was diagnosed during a
      subsequent ER visit. One patient was admitted on postoperative day 4 because of
      constipation. No CD grade III or higher complications were observed for any
      patient. CONCLUSIONS: Robotic unilateral extravesical ureteral reimplantation is
      safe as an outpatient procedure in the pediatric population. Further evaluation
      is warranted to assess its short- and long-term outcomes on a larger scale.

PMID- 30218763
TI  - Can we predict the outcome of oral dissolution therapy for radiolucent renal
      calculi? ; A prospective study.
AB  - PURPOSE: To prospectively, assess the efficacy and predictors of success of oral
      dissolution therapy (ODT) by alkalinization for lucent renal calculi. PATIENTS
      AND METHODS: Patients with radiolucent renal stones were counseled ODT which
      entails oral potassium citrate 20 mEq three times daily, 3 liters of daily fluid
      intake and dietary regimen. Primary study's endpoint was ODT-achieved 6 months
      stone free rate. Other end points included change in stone surface area as
      measured by NCCT at 3 and 6 months. RESULTS: Between February 2015 and January
      2016, among 212 eligible patients agreed to participate, only 182 patients were
      ODT compliant and included in the final analysis. Mean stone surface area at
      enrollment was 1.3 cm3 (range 0.16-11.84). At 3 months, 97(53.2%), 65 (35.7%) and
      20 (11.1%) patients were stone free (ODT responders), partial responders and non
      responders, respectively. ODT-achieved 6 months stone free rate was 83% (97 and
      54 patients after 3 and 6 months ODT, respectively). On regression analysis,
      initial response (3 months) to ODT (p=0.001), lower stone density (p=0.03) and
      higher urine PH at 12 weeks after treatment (p=0.01) independently predict ODT
      response at 6 months. CONCLUSION: Regardless stone size, ODT is an effective
      treatment approach for lucent renal stones. Initial response to ODT after 3
      months is the key factor in determining potential ODT response after 6 months. In
      addition, treatment compliance achieving targeted urine PH and low stone density
      has an independent role in ODT response.

PMID- 30218764
TI  - A Prospective Program to Reduce the Clinical Incidence of Clostridium Difficile
      Colitis Infection after Cystectomy.
AB  - PURPOSE: The development of Clostridium difficile infection after cystectomy is
      associated with significant morbidity and mortality. We implemented a prospective
      screening program to identify asymptomatic carriers of Clostridium difficile and
      assessed its impact on clinical Clostridium difficile infection rates compared to
      historical matched controls. MATERIALS AND METHODS: Prospective Clostridium
      Difficile screening prior to cystectomy began in March 2015. The 380 consecutive
      patients undergoing cystectomy prior to initiation of screening (control cohort)
      were matched based on 5 clinical factors with the 386 patients who underwent
      cystectomy from March 2015 to December 2017 (trial cohort). Screened positive
      patients were placed in contact isolation and treated prophylactically with
      Metronidazole. Multivariable models were built on an intention-to-screen and an
      effectiveness of screening basis to determine if screening reduced the rates of
      symptomatic Clostridium Difficile infections postoperatively. RESULTS: With the
      implementation of the screening protocol, Clostridium difficile infections rates
      declined from 9.4 to 5.5% (OR 0.52, p=0.0268) on an intention-to-screen protocol
      and from 9.2 to 4.9% on an effectiveness of screening protocol (OR 0.46,
      p=0.0174). CONCLUSIONS: Clostridium difficile screening prior to cystectomy is
      associated with a significant decrease in rates of clinically symptomatic
      infections postoperatively. These results should be confirmed in a randomized
      controlled trial.

PMID- 30218765
TI  - Intracerebellar microinjection of histaminergic compounds on locomotor and
      exploratory behaviors in mice.
AB  - The neural histaminergic system innervates the cerebellum, with a high density of
      fibers in the vermis and flocculus. The cerebellum participates in motor
      functions, but the role of the histaminergic system in this function is unclear.
      In the present study, we investigated the effects of intracerebellar histamine
      injections and H1, H2 and H3 receptor antagonist injections (chlorpheniramine,
      ranitidine, and thioperamide, respectively) and H4 receptor agonist (VUF-8430) on
      locomotor and exploratory behaviors in mice. The cerebellar vermis of male mice
      was implanted with guide cannula. After three days of recovery,the animals
      received microinjections of saline or histamine (experiment1), saline or
      chlorpheniramine (experiment 2), saline or ranitidine(experiment 3), saline or
      thioperamide (experiment 4), and saline or VUF-8430 (experiment 5) in different
      concentrations. Five minutes postinjection,the open field test was performed. The
      data were analyzed using one-way ANOVA and Duncan's post hoc test. The
      microinjections of histamine, ranitidine or thioperamide did not lead any
      behavioral effects at the used doses. In contrast, animals that received
      chlorpheniramine at the highest dose (0.16 nmol) and VUF-8430 at the highest dose
      (1.48 nmol)were more active in the open field apparatus, with an increase in the
      number of crossed quadrants, number of rearings and time spent in the central
      area of the arena, suggesting that chlorpheniramine and VUF-8430 modulates
      locomotor and exploratory behaviors in mice.

PMID- 30218766
TI  - Prox1 mRNA expression in the medial cortex of the turtle (Pseudemys scripta
      elegans).
AB  - The medial cortex of the cerebrum in reptiles is thought to be homologous to the
      mammalian dentate gyrus, based on cytoarchitectures, fiber connections, and
      neurochemical profiles. To support this hypothesis, we examined the mRNA
      expression of vesicular glutamate transporter 1 (vGluT1), a glutamatergic gene
      marker, and Prox1, a selective gene marker for granule cells of the dentate
      gyrus, in the turtle medial cortex (zone 2). Reverse transcription-polymerase
      chain reaction revealed the presence of both mRNAs in the turtle cerebrum. In
      situ hybridization of zone 2, which is a layer of densely packed neurons in Nissl
      stains, intensely expressed vGluT1 and Prox1. In zone 3, which is a loosely
      packed layer, vGluT1 was intensely expressed, whereas Prox1 signals gradated from
      strong to negative toward zone 4. These findings demonstrate that zone 2 contains
      glutamatergic neurons and expresses Prox1 mRNA and suggest that zone 2 in the
      turtle cerebrum is homologous to the mammalian dentate gyrus.

PMID- 30218767
TI  - Fatigue-induced decline in low-frequency common input to bilateral and unilateral
      plantar flexors during quiet standing.
AB  - Plantar flexor muscles play a crucial role in maintaining balance during quiet
      standing. The purpose of this study was to investigate the effect of their
      fatigue on common input to these muscles, using a coherence analysis. Thirteen
      healthy young male adults stood quietly before and after a fatigue protocol
      consisting of a heel raise exercise. Center of pressure (COP) displacement and
      electromyograms (EMGs) from the bilateral medial gastrocnemius and soleus muscles
      were recorded. EMG-EMG coherences between the bilateral homologous muscles
      (bilateral coherence) and within the unilateral muscles (unilateral coherence) in
      the right leg were calculated. Anteroposterior and mediolateral COP speeds,
      mediolateral COP SD, and 95% confidence ellipse area were larger in post- than
      pre-fatigue condition. Bilateral and unilateral coherences in delta band, that
      reflect comodulation of muscle activation, and bilateral coherence in alpha band,
      that is supposedly associated with the subcortical inputs, were smaller in post-
      than pre-fatigue condition. Unilateral coherences in alpha and beta band,
      reflecting physiological tremor and corticospinal drive, respectively, were not
      different between pre- and post-fatigue conditions. It is suggested that the low
      frequency common input to the plantar flexor muscles is reduced following the
      fatiguing contraction during quiet standing, likely by a change in the postural
      control strategy.

PMID- 30218768
TI  - Spinal mechanisms of pudendal nerve stimulation-induced inhibition of bladder
      hypersensitivity in rats.
AB  - Bilateral electrical pudendal nerve stimulation (bPNS) reduces bladder
      hypersensitivity in rat models of bladder pain and anecdotally reduces pain in
      humans with pelvic pain of urologic origin. The spinal neurochemical mechanisms
      of this antinociception are unknown. In the present study, bladder
      hypersensitivity was produced by neonatal bladder inflammation in rat pups
      coupled with a second inflammatory insult as an adult. Visceromotor responses
      (VMRs; abdominal muscle contractions) to urinary bladder distension (UBD) were
      used as a nociceptive endpoint under urethane-isoflurane anesthesia. bPNS
      consisted of bilateral biphasic electrical stimulation of the mixed motor/sensory
      component of the pudendal nerves. Following determination of the inhibitory
      effect of bPNS on VMRs, pharmacological antagonists were administered via an
      intrathecal catheter onto the lumbosacral spinal cord and bPNS effects on VMRs
      redetermined. bPNS resulted in statistically significant inhibition of VMRs to
      UBD in hypersensitive rats that was statistically reduced by the intrathecal
      administration of methysergide, WAY100636, CGP35348 and strychnine but was
      unaffected by naloxone, bicuculline, phentolamine, ondansetron and normal saline.
      This study suggests that inhibitory effects of bPNS may include serotonergic,
      GABA-B-ergic and glycinergic mechanisms suggesting the potential for interaction
      of the neuromodulatory effect with concommitant drug therapies.

PMID- 30218769
TI  - Systematic comparison between a wireless EEG system with dry electrodes and a
      wired EEG system with wet electrodes.
AB  - Recent advances in dry electrodes technology have facilitated the recording of
      EEG in situations not previously possible, thanks to the relatively swift
      electrode preparation and avoidance of applying gel to subject's hair. However,
      to become a true alternative, these systems should be compared to state-of-the
      art wet EEG systems commonly used in clinical or research applications. In our
      study, we conducted a systematic comparison of electrodes application speed,
      subject comfort, and most critically electrophysiological signal quality between
      the conventional and wired Biosemi EEG system using wet active electrodes and the
      compact and wireless F1 EEG system consisting of dry passive electrodes. All
      subjects (n = 27) participated in two recording sessions on separate days, one
      with the wet EEG system and one with the dry EEG system, in which the session
      order was counterbalanced across subjects. In each session, we recorded their EEG
      during separate rest periods with eyes open and closed followed by two versions
      of a serial visual presentation target detection task. Each task component allows
      for a neural measure reflecting different characteristics of the data, including
      spectral power in canonical low frequency bands, event-related potential
      components (specifically, the P3b), and single trial classification based on
      machine learning. The performance across the two systems was similar in most
      measures, including the P3b amplitude and topography, as well as low frequency
      (theta, alpha, and beta) spectral power at rest. Both EEG systems performed well
      above chance in the classification analysis, with a marginal advantage of the wet
      system over the dry. Critically, all aforementioned electrophysiological metrics
      showed significant positive correlations (r = 0.54-0.89) between the two EEG
      systems. This multitude of measures provides a comprehensive comparison that
      captures different aspects of EEG data, including temporal precision, frequency
      domain as well as multivariate patterns of activity. Taken together, our results
      indicate that the dry EEG system used in this experiment can effectively record
      electrophysiological measures commonly used across the research and clinical
      contexts with comparable quality to the conventional wet EEG system.

PMID- 30218770
TI  - Individual differences in analogical reasoning revealed by multivariate task
      based functional brain imaging.
AB  - Although analogical reasoning (AR) plays a central role in higher-level cognition
      and constitutes a key source of individual differences in intellectual ability,
      the neural mechanisms that account for individual differences in AR remain to be
      well characterized. Here we investigated individual differences in AR within a
      large sample (n = 229), using multivariate fMRI analysis (a simple multiple
      kernel learning machine). The individual AR capability was positively correlated
      with activation level in a prefrontal executive network and a visuospatial
      network. Notably, the best predictors of individual differences in AR within
      these networks were activation in the dorsomedial prefrontal cortex (response
      selection) and the lingual gyrus (visual feature mapping). In contrast, AR
      capability was negatively correlated with activation in the default mode network.
      The implications of the reported findings are twofold: (i) Individual differences
      in AR depend on multiple executive and visuospatial brain regions, where their
      respective contributions are contingent upon the individuals' cognitive skills;
      (ii) Brain regions associated with individual differences in AR only partially
      overlap with brain regions sensitive to the associated task demands (i.e., brain
      regions sensitive to the analogy relational complexity, at the group-level). We
      discuss implications of such brain organization supporting AR as an example for
      brain architecture underlying higher-level cognitive processes.

PMID- 30218771
TI  - Regulation of cellular iron metabolism: Iron-dependent degradation of IRP by
      SCFFBXL5 ubiquitin ligase.
AB  - Because of essentiality and toxicity of iron in our body, iron metabolism is
      tightly regulated in cells. In mammalian cells, iron regulatory protein 1 and 2
      (IRP1 and IRP2) are the central regulators of cellular iron metabolism. IRPs
      regulate iron metabolism by interacting with the RNA stem-loop structures, iron
      responsive elements (IREs), found on the transcripts encoding proteins involved
      in iron metabolism only in iron depleted condition. It is also well-known that
      the ubiquitin system plays central roles in cellular iron regulation because both
      IRPs having the IRE binding activity are recognized and ubiquitinated by the
      SCFFBXL5 ubiquitin ligase in condition of iron-replete. FBXL5, which is a
      substrate recognition subunit of SCFFBXL5, senses iron availability via its
      hemerythrin-like domain. In this small article, current understanding of the
      roles of SCFFBXL5-mediated degradation of IRPs played in cellular iron metabolism
      is discussed.

PMID- 30218772
TI  - An intronic single nucleotide polymorphism in the MUTYH gene is associated with
      increased risk for HCV-induced hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: The role of base excision repair genes in human
      hepatocarcinogenesis has not yet been explored. Here, we investigated
      relationships between variants of these genes and the risk of developing
      hepatocellular carcinoma (HCC). METHODS: Nineteen tagging SNPs in base excision
      repair genes (including MUTYH, OGG1 and MTH1) were genotyped using iPLEX assays;
      one significant SNP was found and confirmed in Japanese patients with chronic
      hepatitis C (CHC) (n = 38 HCC and 55 controls). The effects of modifying the
      intronic variants were determined by luciferase assays. MUTYH-null mice were used
      to examine the involvement of oxidative stress and DNA repair enzymes in
      hepatocarcinogenesis. RESULTS: Significant associations were found for a single
      intron SNP (rs3219487) in the MUTYH gene. The risk of developing HCC in patients
      with A/A or G/A genotypes was higher than in those with the G/G genotype (OR =
      9.27, 95% CI = 2.39 -32.1, P = 0.0005). MUTYH mRNA levels in both peripheral
      mononuclear cells were significantly lower in G/A or A/A genotyped subjects (P =
      0.0157 and 0.0108, respectively). We found that -2000 in the MUTYH promoter
      region is involved in enhanced expression of MUTYH by insertion of a major allele
      sequence of rs3219487. Liver tumors were observed in MUTYH-null mice after 12
      months' high iron diet, but no tumors developed when dietary anti-oxidant (N
      Acetyl-L-cysteine) was also provided. CONCLUSIONS: CHC patients with the
      rs3219487 adenine allele had a significantly increased risk of developing HCC.
      MUTYH-null mice with iron-associated oxidative stress were susceptible to
      development of liver tumors unless prevented by dietary anti-oxidants.

PMID- 30218773
TI  - Caffeic acid attenuates rat liver injury after transplantation involving PDIA3
      dependent regulation of NADPH oxidase.
AB  - The transplanted liver inevitably suffers from ischemia reperfusion (I/R) injury,
      which represents a key issue in clinical transplantation determining early
      outcome and long-term graft survival. A solution is needed to deal with this
      insult. This study was undertaken to explore the effect of Caffeic acid (CA), a
      naturally occurring antioxidant, on I/R injury of grafted liver and the
      mechanisms involved. Male Sprague-Dawley rats underwent orthotopic liver
      transplantation (LT) in the absence or presence of CA administration. In vitro,
      HL7702 cells were subjected to hypoxia/reoxygenation. LT led to apparent hepatic
      I/R injury, manifested by deteriorated liver function, microcirculatory
      disturbance and increased apoptosis, along with increased PDIA3 expression and
      nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase activity, and
      membrane translocation of NADPH oxidase subunits. Treatment with CA attenuated
      the above alterations. siRNA/shRNA-mediated knockdown of PDIA3 in HL7702 cells
      and rats played the same role as CA not only in inhibiting ROS production and
      NADPH oxidase activity, but also in alleviating hepatocytes injury. CA protects
      transplanted livers from injury, which is likely attributed to its protection of
      oxidative damage by interfering in PDIA3-dependent activation of NADPH oxidase.

PMID- 30218775
TI  - Evidence of introgressive hybridization between Stenella coeruleoalba and
      Delphinus delphis in the Greek Seas.
AB  - Natural interspecific hybridization might be more important for the evolutionary
      history and speciation of animals than previously thought, considering several
      demographic and life history traits as well as habitat disturbance as factors
      that promote it. In this aspect, cetaceans comprise an interesting case in which
      the occurrence of sympatric species in mixed associations provides excellent
      opportunities for interspecific sexual interaction and the potential for
      hybridization. Here, we present evidence of natural hybridization for two
      cetacean species commonly occurring in the Greek Seas (Stenella coeruleoalba and
      Delphinus delphis), which naturally overlap in the Gulf of Corinth by analyzing
      highly resolving microsatellite DNA markers and mitochondrial DNA sequences in
      skin samples from 45 individuals of S. coeruleoalba, 12 D. delphis and three
      intermediate morphs. Employing several phylogenetic and population genetic
      approaches, we found 15 individuals that are potential hybrids including the
      three intermediate morphs, verifying the occurrence of natural hybridization
      between species of different genera. Their hybrids are fertile and able to
      reproduce not only with the other hybrids but also with each of the two-parental
      species. However, current evidence does not allow firm conclusions whether
      hybridization might constitute a step towards the generation of a new species
      and/or the swan song of an already existing species (i.e., D. delphis). Given
      that the focal species form mixed pods in several areas of Mediterranean, this
      study is an excellent opportunity to understand the mechanisms leading to
      hybridization in the context of gene flow and urges for the evaluation of the
      genetic status of common dolphins in the Mediterranean.

PMID- 30218774
TI  - Glaciation-based isolation contributed to speciation in a Palearctic alpine
      biodiversity hotspot: Evidence from endemic species.
AB  - Organisms are unevenly distributed on earth and the evolutionary drivers of that
      have puzzled ecologists and evolutionary biologists for over a century. Even
      though many studies have focused on the mechanisms of unevenly distributed fauna
      and flora, there remains much to learn about the evolutionary drivers behind
      biodiversity hotspots. In the Tibetan Plateau and Hengduan Mountains, a
      biodiversity hotspot in the Palearctic realm, alpine uplift cannot be the driver
      for recent speciation (<two million years ago), researchers broadly refer to
      climatic oscillations driven biodiversity, however, the specific individual roles
      of glaciation and inter-glaciation periods in promoting biodiversity is unclear.
      The current study focuses on investigating whether recent speciation between two
      close-related avian species (White eared pheasant, Crossoptilon crossoptilon and
      Tibetan eared pheasant, C. harmani) was driven by glaciation-based isolation or
      by dispersal during inter-glaciation. To answer this question, we combined Sanger
      sequencing and next-generation sequencing technology to estimate population
      structure, phylogeny, divergence time, demographic history and potential
      historical distributions for C. crossoptilon and C. harmani, which are endemic to
      China. We found that the divergence time between these two species and within C.
      crossoptilon are both during glaciation periods. During glaciation periods, both
      C. harmani and C. crossoptilon experienced isolated distributions and extreme
      bottlenecks. The results of this study suggest that glaciation-based isolation
      contributed to recent speciation in the Tibetan Plateau and Hengduan Mountains,
      and sheds light on our understanding of the evolutionary mechanisms that
      contributed to the formation of Palearctic alpine biodiversity hotspots and
      unevenly distributed species richness pattern.

PMID- 30218776
TI  - Relating the mechanical properties of atherosclerotic calcification to
      radiographic density: A nanoindentation approach.
AB  - Calcification morphology can determine atherosclerotic plaque stability and is
      associated with increased failures rates for endovascular interventions.
      Computational efforts have sought to elucidate the relationship between
      calcification and plaque rupture in addition to predicting tissue response during
      aggressive revascularisation techniques. However, calcified material properties
      are currently estimated and may not reflect real tissue conditions. The objective
      of this study is to correlate calcification mechanical properties with three
      radiographic density groups obtained from corresponding Computed Tomography (CT)
      images. Seventeen human plaques extracted from carotid (n = 10) and peripheral
      lower limb (n = 7) arteries were examined using micro-computed tomography (uCT),
      simultaneously locating the calcified deposits within their internal structure
      and quantifying their densities. Three radiographic density groups were defined
      based on the sample density distribution: (A) 130-299.99 Hounsfield Units (HU),
      (B) 300-449.99 HU and (C) >450 HU. Nanoindentation was employed to determine the
      Elastic Modulus (E) and Hardness (H) values within the three density groups.
      Results reveal a clear distinction between mechanical properties with respect to
      radiographic density groups (p < 0.0005). No significant differences exist in the
      density-specific behaviours observed between carotid and peripheral samples.
      Previously defined calcification classifications indicate an association with
      specific radiographic density patterns. Scanning Electron Microscopy (SEM)
      examination revealed that density group A regions consist of both calcified and
      non-calcified tissues. Further research is required to define the radiographic
      thresholds which identify varying degrees of tissue calcification. This study
      demonstrates that the mechanical properties of fully mineralised atherosclerotic
      calcification emulate that of bone tissues (17-25 GPa), affording computational
      models with accurate material parameters. STATEMENT OF SIGNIFICANCE: Global
      mechanical characterisation techniques disregard the heterogeneous nature of
      atherosclerotic lesions. Previous nanoindentation results for carotid
      calcifications have displayed a wide range. This study evaluates calcification
      properties with respect to radiographic density obtained from Micro-CT images.
      This is the first work to characterise calcifications from peripheral lower limb
      arteries using nanoindentation. Results demonstrate a strong positive correlation
      between radiographic density and calcification mechanical properties.
      Characterising calcifications using their density values provides clarity on the
      variation in published properties for calcified tissues. Furthermore, this study
      confirms the hypothesis that fully calcified plaque tissue behaviour similar to
      that of bone. Appropriate material parameters for calcified tissues can now be
      employed in computational simulations.

PMID- 30218777
TI  - Chitosan/silk fibroin modified nanofibrous patches with mesenchymal stem cells
      prevent heart remodeling post-myocardial infarction in rats.
AB  - Poor functional survival of the engrafted stem cells limits the therapeutic
      efficacy of stem-cell-based therapy for myocardial infarction (MI). Cardiac patch
      based system for cardiac repair has emerged as a potential regenerative strategy
      for MI. This study aimed to design a cardiac patch to improve the retention of
      the engrafted stem cells and provide mechanical scaffold for preventing the
      ventricular remodeling post-MI. The patches were fabricated with electrospinning
      cellulose nanofibers modified with chitosan/silk fibroin (CS/SF) multilayers via
      layer-by-layer (LBL) coating technology. The patches engineered with adipose
      tissue-derived mesenchymal stem cells (AD-MSCs) (cell nano-patch) were adhered to
      the epicardium of the infarcted region in rat hearts. Bioluminescence imaging
      (BLI) revealed higher cell viability in the cell nano-patch group compared with
      the intra-myocardial injection group. Echocardiography demonstrated less
      ventricular remodeling in cell nano-patch group, with a decrease in the left
      ventricular end-diastolic volume and left ventricular end-systolic volume
      compared with the control group. Additionally, left ventricular ejection fraction
      and fractional shortening were elevated after cell nano-patch treatment compared
      with the control group. Histopathological staining demonstrated that cardiac
      fibrosis and apoptosis were attenuated, while local neovascularization was
      promoted in the cell nano-patch group. Western blot analysis illustrated that the
      expression of biomarkers for myocardial fibrosis (TGF-beta1, P-smad3 and Smad3)
      and ventricular remodeling (BNP, beta-MHC: alpha-MHC ratio) were decreased in
      cell nano patch-treated hearts. This study suggests that CS/SF-modified
      nanofibrous patches promote the functional survival of engrafted AD-MSCs and
      restrain ventricular remodeling post-MI through attenuating myocardial fibrosis.
      STATEMENT OF SIGNIFICANCE: First, the nanofibrous patches fabricated from the
      electrospun cellulose nanofibers could mimic the natural extracellular matrix
      (ECM) of hearts to improve the microenvironment post-MI and provide three
      dimensional (3D) scaffolds for the engrafted AD-MSCs. Second, CS and SF which
      have exhibited excellent properties in previous tissue engineering research, such
      as nontoxicity, biodegradability, anti-inflammatory, strong hydrophilic nature,
      high cohesive strength, and intrinsic antibacterial properties further optimized
      the biocompatibility of the nanofibrous patches via LBL modification. Finally,
      the study revealed that beneficial microenvironment and biomimetic ECM improve
      the retention and viability of the engrafted AD-MSCs and the mechanical action of
      the cell nano-patches for the expanding ventricular post-MI leads to suppression
      of HF progression by inhibition of ventricular remodeling.

PMID- 30218778
TI  - Inflammatory response and biomechanical properties of coaxial scaffolds for
      engineered skin in vitro and post-grafting.
AB  - Engineered skin (ES) offers many advantages over split-thickness skin autografts
      for the treatment of burn wounds. However, ES, both in vitro and after grafting,
      is often significantly weaker, less elastic and more compliant than normal human
      skin. Biomechanical properties of ES can be tuned in vitro using electrospun co
      axial (CoA) scaffolds. To explore the potential for coaxial scaffold-based ES use
      in vivo, two CoA scaffolds were fabricated with bioactive gelatin shells and
      biodegradable synthetic cores of polylactic acid (PLA) and polycaprolactone
      (PCL), and compared with gelatin monofilament scaffolds. Fibroblast and
      macrophage production of inflammatory cytokines interleukin 6 (IL-6) and
      transforming growth factor beta-1 was significantly higher when cultured on PLA
      and PCL monofilament scaffolds compared to gelatin monofilament scaffolds. The
      core-shell fiber configuration significantly reduced production of pro
      inflammatory cytokines to levels similar to those of gelatin monofilament
      scaffolds. In vitro, ES mechanical properties were significantly enhanced using
      CoA scaffolds; however, after grafting CoA- and gelatin-based ES to full
      thickness excisional wounds on athymic mice, the in vitro mechanical advantage of
      CoA grafts was lost. A substantially increased inflammatory response to CoA-based
      ES was observed, with upregulation of IL-6 expression and a significant M2
      macrophage presence. Additionally, expression of matrix metalloproteinase I was
      upregulated and collagen type I alpha 1 was downregulated in CoA ES two weeks
      after grafting. These results suggest that while coaxial scaffolds provide the
      ability to regulate biomechanics in vitro, further investigation of the
      inflammatory response to core materials is required to optimize this strategy for
      clinical use. STATEMENT OF SIGNIFICANCE: Engineered skin has been used to treat
      very large burn injuries. Despite its ability to heal these wounds, engineered
      skin exhibits reduced biomechanical properties making it challenging to
      manufacture and surgically apply. Coaxial fiber scaffolds have been utilized to
      tune the mechanical properties of engineered skin while maintaining optimal
      biological properties but it is not known how these perform on a patient
      especially with regards to their inflammatory response. The current study
      examines the biomechanical and inflammatory properties of coaxial scaffolds and
      uniaxial scaffolds in vitro and in vivo. The results show that the biological
      response to the scaffold materials is a critical determinant of tissue properties
      after grafting with reduced inflammation and rapid scaffold remodeling leading to
      stronger skin.

PMID- 30218779
TI  - Incorporation of hydroxyproline in bacterial collagen from Streptococcus
      pyogenes.
AB  - Bacterial collagen-like proteins differ from vertebrate collagens in that they do
      not contain hydroxyproline, which is seen as a characteristic of the vertebrate
      collagens, and which provides a significant contribution to the stability of the
      collagen triple-helix at body temperature. Despite this difference, the bacterial
      collagens are stable at around body temperature through inclusion of other
      stabilising sequence elements. Another difference is the lack of aggregation, and
      certain vertebrate collagen binding domains that can be introduced into the
      bacterial sequence lack full function when hydroxyproline is absent. In the
      present study we have demonstrated that a simple method utilising co
      translational incorporation during fermentation can be used to incorporate
      hydroxyproline into the recombinant bacterial collagen. The presence and amount
      of hydroxyproline incorporation was shown by amino acid analysis and by mass
      spectrometry. A small increase in thermal stability was observed using circular
      dichroism spectroscopy. STATEMENT OF SIGNIFICANCE: Recombinant bacterial
      collagens provide a new opportunity for biomedical materials as they are readily
      produced in large quantity in E. coli. Unlike animal collagens, they are stable
      without the need for inclusion of a secondary modification system for
      hydroxyproline incorporation. In animal collagens, however, introduction of
      hydroxyproline is essential for stability and is also important for functional
      molecular interactions within the mammalian extracellular matrix. The present
      study has shown that hydroxyproline can be readily introduced into recombinant S.
      pyogenes bacterial collagen through direct co-translational incorporation of this
      modified imino acid during expression using the codons for proline in the
      introduced gene construct. This hydroxylation further improves the stability of
      the collagen and is available to enhance any introduced molecular functions.

PMID- 30218780
TI  - Tuning the bioactivity of bone morphogenetic protein-2 with surface
      immobilization strategies.
AB  - Bone morphogenetic protein-2 (BMP-2) involved therapy is of great potential for
      bone regeneration. However, its clinical application is restricted due to the
      undesirable bioactivity and relevant complications in vivo. Immobilization of
      recombinant BMP-2 (rhBMP-2) is an efficient strategy to mimic natural
      microenvironment and retain its bioactivity. Herein, we present evidences
      indicating that osteoinductive capacity of rhBMP-2 can be regulated via variant
      immobilizing approaches. Three representative superficial immobilizing models
      were employed to fabricate rhBMP-2-immobilized surfaces including physical
      adsorption (Au/rhBMP-2), covalent grafting (rhBMP-2-SAM-Au) and heparin binding
      (Hep-SAM-Au/rhBMP-2) (SAM: self-assembled monolayer). Loading capacity, releasing
      behavior, osteogenic differentiation and signaling pathways involved, as well as
      the cellular recognition of rhBMP-2 under various immobilization modes were
      systematically investigated. As a result, disparate immobilizing approaches not
      only have effects on loading capacity, but also lead to disparity of
      osteoinduction at the same dosage. Notably, heparin could reinforce the
      recognition between rhBMP-2 and its receptors (BMPRs) whereas weaken its binding
      to its antagonist Noggin. Owing to this "selective" binding feature, the
      favorable osteoinduction and maximum ectopic bone formation can be achieved with
      the heparin-binding approach. In particular, manipulation of orientation-mediated
      BMP-2-cell recognition efficiency may be a potential target to design more
      therapeutic efficient rhBMP-2 delivery system. STATEMENT OF SIGNIFICANCE: Bone
      morphogenetic protein-2 (BMP-2) is crucial in bone regeneration. However, its
      clinical application is challenged due to its shorten half-life and supra
      physiological dose associated complications. In this study, three representative
      superficial immobilizing patterns were fabricated through physical adsorption,
      covalent grafting and electrostatic interaction with heparin respectively. We
      provided evidences indicating an dose-dependent osteoinductive capacity of
      immobilized BMP-2. Further, a possible mechanism of rhBMP-2-cell recognition at
      the interface was presented, highlighting the superior effect of heparin on rhBMP
      2 bioactivity. Finally, We proposed a dual mechanism of tuning the bioactivity of
      immobilized rhBMP-2 through surface immobilization approaches: regulation of the
      saturated loading capacity and orientation-mediated rhBMP-2-cell recognition.
      These results provide novel insights into designing criterion of efficient
      delivery vehicle for rhBMP-2.

PMID- 30218781
TI  - Identification of nonalcoholic fatty liver disease following pancreatectomy for
      noninvasive intraductal papillary mucinous neoplasm.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) following pancreatectomy is
      a potential cause of long term morbidity in patients undergoing pancreatic
      resection with curative intent. Prior studies have reported an incidence of NAFLD
      up to 30% following pancreatectomy but the investigated cohorts were typically a
      mix of benign and malignant disease. Here we examined the incidence of NAFLD in a
      homogenous cohort of patients following pancreatectomy for benign intraductal
      papillary mucinous neoplasm (IPMN). METHODS: A retrospective review of patients
      who underwent pancreatic resection for IPMN from 2000 to 2016 was performed. Post
      pancreatectomy CT/MRI scans were obtained as standard surveillance. We
      investigated changes in the liver parenchymal density on post surgical imaging to
      estimate the frequency with which NAFLD occurred. Radiographic criteria for NAFLD
      included Hounsfield units less than 40 on CT or liver:spleen ratio <0.9 on CT or
      MRI. Fischer's exact test, Kruskal-Wallis test, and logistic regression were
      performed. RESULTS: Our study cohort included 109 patients who underwent
      pancreatectomy for nonmalignant intraductal papillary mucinous neoplasm with no
      evidence of NAFLD preoperatively and at least 6 months follow-up. Mean follow-up
      was 52 months (range 8-130/months). The incidence of postoperative NAFLD was
      17/109 (15.6%). Most cases occurred within 12 months of pancreatectomy. On
      multivariate analysis, proximal pancreatectomy (pancreaticoduodenectomy) and
      development of atrophy of the pancreas remnant were significant risk factors for
      development of hepatic steatosis (p < 0.05). CONCLUSION: Patients undergoing
      pancreatectomy for benign disease have a significant risk of developing NAFLD but
      the frequency is lower than previously reported in cohorts that included
      individuals with malignant disease. Highest risk was observed in individuals who
      underwent pancreaticoduodenectomy or developed pancreatic atrophy. Further
      investigations to define the mechanisms that promote steatosis and interventions
      to prevent subsequent morbidity from NAFLD are warranted.

PMID- 30218782
TI  - Inflammation in individuals with schizophrenia - Implications for neurocognition
      and daily function.
AB  - Individuals with schizophrenia display substantial deficits in neurocognition,
      resulting in poor daily functioning and disability. Recent reports have suggested
      that neurocognitive dysfunction in this population is linked to increased
      inflammation. However, there is paucity of evidence supporting this link, as well
      as lack of information about the putative link of inflammation to daily
      functioning. We examined neurocognition (MCCB) and daily functioning (SLOF), as
      well as inflammatory markers (TNF-alpha, IL-6, IL-1beta, and IL-12p70) in 41
      individuals with schizophrenia. Poor neurocognition was significantly associated
      with increased peripheral TNF-alpha and IL-12p70 (r = -0.44 and r = -0.38,
      respectively, controlling for BMI, depression and antipsychotic medication).
      Notably, difficulties with daily functioning were significantly associated with
      increased peripheral TNF-alpha (r = -0.51) and a trend with increased IL-12p70.
      Our findings support previous hypotheses linking neurocognitive impairment to
      increased inflammation in individuals with schizophrenia. Our results extend
      these associations in this population, linking inflammation to poor daily
      functioning in this population.

PMID- 30218783
TI  - Myelination induction by a histamine H3 receptor antagonist in a mouse model of
      preterm white matter injury.
AB  - Fifteen million babies are born preterm every year and a significant number
      suffer from permanent neurological injuries linked to white matter injury (WMI).
      A chief cause of preterm birth itself and predictor of the severity of WMI is
      exposure to maternal-fetal infection-inflammation such as chorioamnionitis. There
      are no neurotherapeutics for this WMI. To affect this healthcare need, the
      repurposing of drugs with efficacy in other white matter injury models is an
      attractive strategy. As such, we tested the efficacy of GSK247246, an H3R
      antagonist/inverse agonist, in a model of inflammation-mediated WMI of the
      preterm born infant recapitulating the main clinical hallmarks of human brain
      injury, which are oligodendrocyte maturation arrest, microglial reactivity, and
      hypomyelination. WMI is induced by mimicking the effects of maternal-fetal
      infection-inflammation and setting up neuroinflammation. We induce this process
      at the time in the mouse when brain development is equivalent to the human third
      trimester; postnatal day (P)1 through to P5 with i.p. interleukin-1beta (IL
      1beta) injections. We initiated GSK247246 treatment (i.p at 7 mg/kg or 20 mg/kg)
      after neuroinflammation was well established (on P6) and it was administered
      twice daily through to P10. Outcomes were assessed at P10 and P30 with gene and
      protein analysis. A low dose of GSK247246 (7 mg/kg) lead to a recovery in protein
      expression of markers of myelin (density of Myelin Basic Protein, MBP &
      Proteolipid Proteins, PLP) and a reduction in macro- and microgliosis (density of
      ionising adaptor protein, IBA1 & glial fibrillary acid protein, GFAP). Our
      results confirm the neurotherapeutic efficacy of targeting the H3R for WMI seen
      in a cuprizone model of multiple sclerosis and a recently reported clinical trial
      in relapsing-remitting multiple sclerosis patients. Further work is needed to
      develop a slow release strategy for this agent and test its efficacy in large
      animal models of preterm infant WMI.

PMID- 30218784
TI  - Evolution of a maternal immune activation (mIA) model in rats: Early
      developmental effects.
AB  - Maternal immune activation (mIA) in rodents is rapidly emerging as a key model
      for neurodevelopmental disorders such as autism spectrum disorder (ASD) and
      schizophrenia. Here, we optimise a mIA model in rats, aiming to address certain
      limitations of current work in this field. Specifically, the lack of clear
      evidence for methodology chosen, identification of successful induction of mIA in
      the dams and investigation of male offspring only. We focus on gestational and
      early juvenile changes in offspring following mIA, as detailed information on
      these critical early developmental time points is sparse. Following strain
      (Wistar, Lister Hooded, Sprague Dawley) comparison and selection, and
      polyriboinosinic-polyribocytidylic acid (poly I:C) dose selection (2.5-15 mg/kg
      single or once daily for 5 days), mIA was induced in pregnant Wistar rats with 10
      mg/kg poly I:C i.p. on gestational day (GD) 15. Early morphometric analysis was
      conducted in male and female offspring at GD21 and postnatal day (PD) 21, eight
      dams for each treatment at each time point were used, 32 in total. Subsequent
      microglia analysis was conducted at PD21 in a small group of offspring. Poly I:C
      at 10 mg/kg i.p. induced a robust, but variable, plasma IL-6 response 3 h post
      injection and reduced body weight at 6 h and 24 h post-injection in two separate
      cohorts of Wistar rats at GD15. Plasma IL-6 was not elevated at PD21 in offspring
      or dams. Poly I:C-induced mIA did not affect litter numbers, but resulted in PD21
      pup, and GD21 placenta growth restriction. Poly I:C significantly increased
      microglial activation at PD21 in male hippocampi. We have identified 10 mg/kg
      poly I:C i.p on GD15 as a robust experimental approach for inducing mIA in Wistar
      rats and used this to identify early neurodevelopmental changes. This work
      provides a framework to study the developmental trajectory of disease-relevant,
      sex-specific phenotypic changes in rats.

PMID- 30218785
TI  - Sleep spindles are altered in early- but not late-onset nightmare recallers.
AB  - Nightmares are a common sleep disorder, defined as highly disturbing mentation
      which usually awakens the individual from rapid eye movement (REM) sleep. While
      nightmares are mainly a REM sleep phenomenon, Picard-Deland et al., (2017)
      recently showed an association between nightmare recall and sleep spindles, which
      are a non-rapid eye movement (NREM) oscillatory feature. Their results pointed to
      fewer slow spindles and a higher oscillatory frequency for fast spindles among
      frequent nightmare recallers compared with controls. To test the suggestion that
      nightmares stem from changes to emotional neural circuits arising in early
      childhood (Nielsen, 2017), including early changes in sleep spindles (Scholle et
      al., 2007), we investigated if the spindle features of early-onset nightmare
      recallers (ie, recalling nightmares since childhood) (N = 22), differed from
      those of late-onset nightmare recallers (ie, since adolescence or adulthood) (N =
      11), or from those of controls (N = 23). A retrospective analysis of the sleep
      spindles of 56 participants who had undergone a polysomnographically-recorded
      morning nap revealed that Early starters uniquely exhibited lower slow spindle
      densities in five of six derivations (all p < 0.045) and higher fast spindle
      frequencies in all six derivations (all p < 0.015). These results add precision
      to previously reported findings for Nightmare recallers: spindle differences are
      shown to hold only for Early starters. The lifelong occurrence of nightmares may
      be closely tied to disruptions in the normal development of spindle generation
      processes occurring early in development.

PMID- 30218786
TI  - A structural view of the initiators for chromosome replication.

PMID- 30218787
TI  - Exercise training in childhood cancer: A systematic review and meta-analysis of
      randomized controlled trials.
AB  - INTRODUCTION: Physical capacity and quality of life (QoL) are typically impaired
      in children/adolescents with cancer. Our primary objective was to examine the
      effects of exercise training performed after diagnosis of any type of pediatric
      cancer on physical capacity-related endpoints, survival, disease relapse and
      adverse effects. METHODS: (a) Search and selection criteria: Systematic review in
      Pubmed and Web of Science (until August 2018) of randomized controlled trials
      (RCTs) of exercise interventions in children with cancer during treatment or
      within one year after its end. (b) Data collection: Two authors independently
      identified studies meeting inclusion criteria, extracted data, and assessed risk
      of bias using standardized forms. When needed, we contacted authors to request
      clarifications or additional data. (c) Statistical Analysis: The pooled
      standardized mean differences (SMD) were calculated for those endpoints for which
      a minimum of three RCTs used the same assessment method. We also calculated the
      pooled odds ratio (OR) of dying or having a tumor relapse. RESULTS: Eight RCTs (n
      = 283 patients) were included in the systematic review. Of these, five studies (n
      = 173) could be meta-analyzed. Exercise training during pediatric cancer
      treatment significantly improves patients' functional mobility, as assessed with
      the timed up and down stairs test (SMD: -0.73, p < 0.001) and does not affect
      mortality (OR: 0.85, p = 0.76) or relapse risk (OR: 0.96, p = 0.94). CONCLUSIONS:
      Exercise training in children with cancer improves functional mobility. More RCTs
      analyzing the effects of supervised exercise interventions are needed, as well as
      the development of a core-set of outcomes in pediatric oncology exercise
      research.

PMID- 30218788
TI  - Biliary Tract Cancer: State of the Art and potential role of DNA Damage Repair.
AB  - Biliary tract cancers (BTCs), including cholangiocarcinoma, gallbladder cancer
      and ampullary cancers, are poor-prognosis malignancies. Most patients are
      diagnosed with advanced disease, when treatment is limited to palliative
      chemotherapy. First line chemotherapy is usually administered in the form of
      cisplatin and gemcitabine. Benefit from second line chemotherapy is still to be
      confirmed. Even though new systemic treatment targets have been recognised,
      especially in patients with intrahepatic cholangiocarcinoma (e.g. IDH and FGFR),
      there is an urgent need for novel treatment strategies. Genomic profiling of BTC
      is progressively becoming a reality which allows a better understanding of their
      biology and potential new targets. This review provides an insight into DNA
      Damage Repair (DDR) mechanisms, prevalence of DDR-deficient tumours in BTC, and
      the potential role of DDR in cancer development. Some form of DDR deficiency is
      expected to be present in around 25% of patients with BTC, and this knowledge
      could be exploited to potentially increase response to currently-available
      treatment strategies (chemotherapy, radiotherapy or immunotherapy). For patients
      with DDR-proficient tumours, drug inhibition of DDR could be instituted.

PMID- 30218789
TI  - CT analysis of anatomical distribution of melorheostosis challenges the
      sclerotome hypothesis.
AB  - Melorheostosis (MEL) is a rare disease of high bone mass with patchy skeletal
      distribution affecting the long bones. We recently reported somatic mosaic
      mutations in MAP2K1 in 8 of 15 patients with the disease. The unique anatomic
      distribution of melorheostosis is of great interest. The disease remains limited
      to medial or lateral side of the extremity with proximo-distal progression. This
      pattern of distribution has historically been attributed to sclerotomes (area of
      bone which is innervated by a single spinal nerve level). In a further analysis
      of our study on MEL, 30 recruited patients underwent whole body CT scans to
      characterize the anatomic distribution of the disease. Two radiologists
      independently reviewed these scans and compared it to the proposed map of
      sclerotomes. We found that the disease distribution conformed to the distribution
      of a single sclerotome in only 5 patients (17%). In another 12 patients, the
      lesions spanned parts of contiguous sclerotomes but did not involve the entire
      extent of the sclerotomes. Our findings raise concerns about the sclerotomal
      hypothesis being the definitive explanation for the pattern of anatomic
      distribution in MEL. We believe that the disease distribution can be explained by
      clonal proliferation of a mutated skeletal progenitor cell along the limb axis.
      Studies in mice models on clonal proliferation in limb buds mimic the patterns
      seen in melorheostosis. We also support this hypothesis by the dorso-ventral
      confinement of melorheostotic lesion in a patient with low allele frequency of
      MAP2K1-positive osteoblasts and low skeletal burden of the disease. This suggests
      that the mutation occurred after the formation of dorso-ventral plane. Further
      studies on limb development are needed to better understand the etiology,
      pathophysiology and pattern of disease distribution in all patients with MEL.

PMID- 30218790
TI  - The limitations of using simple definitions of glucocorticoid exposure to predict
      fracture risk: A cohort study.
AB  - PURPOSE: To evaluate the effects of different definitions of glucocorticoid (GC)
      exposure on the magnitude and pattern of fracture risk using the same dataset.
      METHODS: Data from patients with rheumatoid arthritis (RA) were extracted from
      the Clinical Practice Research Datalink, a primary care database with electronic
      health records in the United Kingdom. Patients exposed to oral GCs were matched
      to up to two unexposed patients by age, gender and location. The first
      osteoporotic fracture was identified and adjusted and unadjusted cox proportional
      hazard ratios (HR) and 95% confidence intervals (CI) produced for fracture risk
      following GC therapy using different models of risk attribution. These include
      models demonstrating the effect of dose, duration and recency of GC exposure.
      RESULTS: There were 16,507 patients included. Exposed patients were older and had
      more comorbidities. GC therapy was associated with an increased risk of fracture,
      with the effect size influenced by risk attribution model. The risk of fracture
      decreased with less recent exposure from HR (95% CI) 1.66 (1.27, 2.16) during the
      first month of stopping GCs to 1.11 (0.79, 1.57) for between 1 and 3 months. The
      risk of fracture increased with current daily dose, HR 1.44 (1.17, 1.77) for 5
      9.9 mg prednisolone equivalent dose (PEQ) to 3.02 (1.77, 5.15) for 15-19.9 mg
      PEQ. Risk of fracture increased with cumulative dose, a function of dose and
      duration, from HR 1.22 (1.03, 1.44) for <1 g to 1.83 (1.35, 2.48) for 7.5-10 g.
      CONCLUSION: GC exposure was associated with excess fracture risk, with effect
      size differing according to definition of exposure. This highlights the need to
      incorporate all exposure dimensions (dose, duration and recency) in these
      patient's fracture risk assessments.

PMID- 30218791
TI  - Glucose dependent miR-451a expression contributes to parathyroid hormone mediated
      osteoblast differentiation.
AB  - Parathyroid hormone (PTH; amino acid 1-34, known as teriparatide) has reported
      promoting differentiation and glucose uptake in osteoblasts. However, how PTH
      regulates glucose metabolism to facilitate osteoblast differentiation is not
      understood. Here, we report that PTH promotes glucose dependent miR-451a
      expression which stimulates osteoblast differentiation. In addition to glucose
      uptake, PTH suppresses AMPK phosphorylation via PI3K-mTOR-AKT axis thereby
      preventing phosphorylation and inactivation of octamer-binding transcription
      factor 1 (OCT-1) which has been reported to act on the promoter region of miR
      451a. Modulation of AMPK activity controls miR-451a levels in differentiating
      osteoblasts. Moreover, pharmacological inhibition of PI3K-mTOR-AKT axis
      suppressed miR-451a via increased AMPK activity. We report that this glucose
      regulated miRNA is an anabolic target and transfection of miR-451a mimic induces
      osteoblast differentiation and mineralization in vitro. These actions were
      mediated through the suppression of Odd-skipped related 1 (Osr1) and activation
      of Runx2 transcription. When injected in vivo, the miR-451a mimic significantly
      increased osteoblastogenesis, mineralization, reversed ovariectomy induced bone
      loss and improved bone strength. Together, these findings suggest that enhanced
      osteoblast differentiation associated with bone formation in case of PTH therapy
      is also a consequence of elevated miR-451a levels via glucose regulation.
      Consequently, this miRNA has the potential to be a therapeutic target for
      conditions of bone loss.

PMID- 30218792
TI  - Accumulation of 152+154Eu(III) by Aspergillus sydowii and Trichoderma harzianum.
AB  - Radionuclides-resistant filamentous fungi were isolated from radionuclides'
      contaminated soils. Effects of contact time, mycelia dosage, pH, ionic strength
      and thiol compounds on 152+154Eu(III) accumulation on two kinds of filamentous
      fungi (Aspergillus sydowii and Trichoderma harzianum, denoted as A. sydowii and
      T. harzianum, respectively) were investigated by batch techniques. The maximum
      tolerance to Eu(III) concentration of A. sydowii and T. harzianum reached 3000
      mg/L and 3500 mg/L, and the Eu(III) accumulation on A. sydowii and T. harzianum
      can be fitted better with the pseudo-second-order kinetic model, respectively.
      Filamentous fungi were characterized by FT-IR and acid base titrations, and
      morphological structures of mycelia changed obviously under Eu(III) stress by SEM
      and TEM analysis. The results suggested that filamentous fungi could play an
      important role in the migration and transformation of radionuclides in the
      environment.

PMID- 30218793
TI  - Calibration of forest 137Cs cycling model "FoRothCs" via approximate Bayesian
      computation based on 6-year observations from plantation forests in Fukushima.
AB  - Predicting the environmental fate of 137Cs in forest ecosystems along with the
      concentrations of 137Cs in tree parts are important for the managements of
      radioactively contaminated forests. In this study, we calibrate the Forest RothC
      and Cs model (FoRothCs), a forest ecosystem 137Cs dynamics model, using
      observational data obtained over six years from four forest sites with different
      levels of 137Cs contamination from Fukushima Prefecture. To this end, we applied
      an approximate Bayesian computation (ABC) technique based on the observed 137Cs
      concentrations (Bq kg-1) of five compartments (leaf, branch, stem, litter, and
      soil) in a Japanese cedar plantation. The environmental decay (increment)
      constants of the five compartments were used as the summary statistics (i.e., the
      metric for model performance) to infer the five parameters related to 137Cs
      transfer processes in FoRothCs. The ABC technique successfully reconciled the
      model outputs with the observed trends in 137Cs concentrations at all sites
      during the study period. Furthermore, the estimated parameters are in agreement
      with the literature values (e.g., the root uptake rates of 137Cs). Our study
      demonstrates that model calibration with ABC based on the trends in 137Cs
      concentrations of multi compartments is useful for reducing the prediction
      uncertainty of 137Cs dynamics in forest ecosystems.

PMID- 30218794
TI  - Cervical Myelopathy Caused by Intracranial Dural Arteriovenous Fistula with Acute
      Worsening After Steroid Administration.
AB  - Intracranial dural arteriovenous fistulas (DAVFs) draining into the perimedullary
      venous system are rare and potentially life-threatening lesions often presenting
      as a myelopathy. The early and proper diagnosis of this rare disease is
      challenging because the symptoms are nonspecific. Acute clinical deterioration in
      patients with spinal DAVFs treated with steroid administration has been
      described. Here we report a case of cervical myelopathy caused by intracranial
      DAVF with acute worsening after steroid administration. The lesion was
      successfully treated with endovascular Onyx embolization.

PMID- 30218795
TI  - Surgical Removal of Skull Base Meningiomas in Symptomatic Elderly Patients.
AB  - OBJECTIVE: Meningiomas frequently occur in elderly patients, and surgical
      treatment is hazardous owing to multiple comorbidities. We report a series of
      elderly patients who were treated with surgical removal of meningiomas and
      compare them with a group of younger patients with similar tumors. METHODS: A
      retrospective study of elderly patients with symptomatic skull base meningiomas
      and a matched control group of younger patients was performed. Medical records,
      operative reports, radiologic examinations, and follow-up data were reviewed.
      Main outcome measures were morbidity, mortality, and Simpson grade. RESULTS: The
      study included 46 patients (23 elderly [age >65 years], 23 younger [age <65
      years]). Average age was 71 years in elderly patients and 48 years in younger
      patients. Mean follow-up period was 32 months and 49 months, respectively.
      Radical removal (Simpson grades I and II) was observed in 83% and 91%,
      respectively. Mortality was 8% and 4%, respectively. Definite cranial nerve
      lesions occurred in 8% and 26%, respectively; cerebrospinal fluid leaks occurred
      in 12.5% and 4%, respectively; hemiparesis occurred in 4% of patients in both
      groups. Glasgow Outcome Scale score of 5 was obtained in 87% and 65.2%,
      respectively. CONCLUSIONS: Elderly patients with symptomatic skull base
      meningiomas should be considered for surgical treatment owing to acceptable
      morbidity and mortality compared with younger patients. Previous comorbidities
      and involvement of neurovascular structures are important factors in the decision
      regarding extent of surgical resection.

PMID- 30218796
TI  - Neuroendoscopic Resection of Trigeminal Schwannoma in the
      Pterygopalatine/Infratemporal Fossa via the Transnasal Perpendicular Plate
      Palatine Bone or Transnasal Maxillary Sinus Approach.
AB  - BACKGROUND: Both the pterygopalatine fossa (PPF) and the infratemporal fossa
      (ITF) lie outside the midline of the skull base. Lesions in the PPF or ITF
      include trigeminal schwannoma (trigeminal schwannoma, TS), which originates from
      the second or third branch of the trigeminal nerve (maxillary nerve or mandibular
      nerve). Due to their typically deep anatomic location, lesions in the PPF or ITF
      can be difficult to treat using traditional surgical approaches. In recent years,
      because of their advantages, which include the fact that they allow the problem
      to be observed close up, neuroendoscopic techniques are increasingly being
      applied in skull base surgery, especially in treatment of lesions around the
      midline of the base of the skull. This study aims to 1) evaluate the
      neuroendoscopic treatment of lesions in PPF or ITF via the transnasal palate bone
      perpendicular plate or transnasal maxillary sinus approach and 2) analyze the
      clinical significance of this approach. METHODS: We retrospectively analyzed 3
      cases of PPF TSs and 1 case of ITF TS treated between January 2015 and May 2017.
      All of the cases underwent neuroendoscopic resection of TSs located in the PPF
      via the nasal perpendicular plate palatine bone (or nasal maxillary sinus)
      approach. RESULTS: Two cases of PPF TSs were characterized by a thin palate bone
      perpendicular plate due to oppressed absorption of the tumor. Therefore the
      endoscopic transnasal palate bone perpendicular plate approach was employed.
      Additionally, 1 case of PPF TSs and 1 case of ITF TS were resected via the
      transnasal maxillary sinus approach. All 4 patients received total resection
      under endoscopy and recovered well after their respective operations without
      cerebrospinal fluid leakage, although 1 patient experienced postoperative dry eye
      symptoms and 1 other patient showed no improvement in facial numbness before and
      after the operation. CONCLUSIONS: Neuroendoscopic surgery performed via the
      transnasal perpendicular plate palatine bone or transnasal maxillary sinus
      approach has its own unique advantages in removing TSs in PPF and in ITF:
      Notably, the tumor can be exposed and dealt with under direct vision, which
      prevents damage to important structures, such as the internal carotid and
      maxillary nerves, while at the same time helping to achieve total removal of TSs.
      Furthermore, by adopting this approach versus traditional skull base surgery,
      postoperative trauma can be reduced significantly, which should be advocated for
      in this time of minimal invasive surgery.

PMID- 30218797
TI  - Preoperative Three-Dimensional Angiography May Reduce Ischemic Complications
      During Clipping of Ruptured Intracranial Aneurysms.
AB  - OBJECTIVE: Microsurgical clipping of aneurysms demands precise spatial
      understanding of aneurysm morphology and vascular geometry. We analyzed the
      impact of preoperative three-dimensional (3D) angiographic imaging on clinical
      and angiographic outcome after clipping of ruptured intracranial aneurysms.
      METHODS: This is a retrospective analysis of consecutive patients who underwent
      microsurgical clipping during the acute phase of subarachnoid hemorrhage between
      2010 and 2017. Surgical planning was made based on two-dimensional (2D) or 3D
      angiographic images. We retrospectively compared complication rates, morbidity,
      and angiographic outcome between these 2 groups. RESULTS: A total of 157 patients
      (mean age: 54.8 +/- 13.1 years) were included in the study. Preoperative 3D
      angiographic imaging was available for 117 cases. The rate of procedure-related
      ischemia was significantly lower in the 3D group (16.2%) than in the 2D group
      (35.0%; P = 0.013). In the multivariate analysis, 2D imaging alone remained as
      independent factor for subsequent brain ischemia (odds ratio: 2.8, 95% confidence
      interval 1.2-6.6; P = 0.018). Favorable outcome (modified Rankin scale <=2) was
      more often attained in the 3D group (70.0%) than in the 2D group (41.9%; P =
      0.002). The rate of complete aneurysm occlusion was not significantly different
      between the 2 groups (P = 0.967). CONCLUSIONS: In our study, accurate operation
      planning using 3D angiography was associated with a lower ischemic complication
      rate after clipping of ruptured intracranial aneurysms, which may potentially
      influence clinical outcome.

PMID- 30218798
TI  - The Intervertebral Disc: Physiology and Pathology of a Brittle Joint.
AB  - BACKGROUND: Intervertebral disc (ID) degeneration represents the number one cause
      for outpatient clinic visits worldwide. Mechanisms are discussed but not yet
      clearly established. Consequently, back pain management is commonly limited to
      symptomatic treatment therapies. OBJECTIVES: The aim of this review is to
      evaluate major progress and to unravel the biology and pathology of ID discogenic
      pain. METHODS: The design of this study is a systematic review. A literature
      search was conducted using Medline, EMBASE, and Google Scholar databases, with no
      time constraints to locate relevant literature. Significant articles (literature
      reviews, therapeutic essays, clinical-human-research studies, animal research,
      and laboratory research) on the intervertebral disc were identified and reviewed.
      The exclusion criteria were the following: case reports and clinical studies with
      <10 patients. RESULTS: Through a dense review of the literature, the ID is
      deciphered and described as a fragile anatomic entity. For this systematic
      review, 132 studies were identified and 79 were retained. The main deterioration
      and alteration mechanisms that lead to the programmed death of the ID are
      summarized. In addition, the large variety of biological therapies that override
      surgical treatment are determined. CONCLUSIONS: The degeneration mechanisms of
      the ID are well defined and decrypted. Although therapies have progressed, none
      has been effective. The regeneration of the ID remains highly challenging because
      of the complexity of its natural composition, microstructure, and mechanical
      properties.

PMID- 30218799
TI  - Utility of Early Postoperative Magnetic Resonance Imaging After Glioblastoma
      Resection: Implications on Patient Survival.
AB  - BACKGROUND: The standard of care for glioblastoma is surgical resection followed
      by combination temozolomide and radiation. Magnetic resonance imaging (MRI) is
      used preoperatively for tumor resection planning. In some instances, MRI is also
      obtained postoperatively to assess for any complications and to determine extent
      of resection. There is some question whether early routine postoperative imaging
      of patients after tumor resection is beneficial to long-term outcomes, especially
      with the increased scrutiny of increasing health care costs. METHODS: In this
      study we retrospectively analyze patients with glioblastoma treated at our
      institution, comparing the difference in overall survival and treatment regimens
      between patients who had early postoperative MRI versus patients who did not.
      RESULTS: We determine that in our cohort of 125 patients, those with early
      postoperative MRI had no statistically significant overall survival difference
      compared with patients with no early postoperative MRI (P = 0.996). The median
      survival for the group with postoperative MRI was 378 days (95% confidence
      interval [CI], 242-443 days), and the median survival for the group without
      postoperative MRI was 308 days (95% CI, 203-445 days). Early postoperative MRI
      also did not significantly alter therapeutic regimens. CONCLUSIONS: Although
      early postoperative MRI may not significantly affect patient overall survival
      from a statistical standpoint or therapeutic regimens, this type of imaging may
      be important to hone resident and attending skill. We encourage other
      institutions to perform similar analyses to determine the overall survival
      benefit of early postoperative imaging after glioma resection for patients with
      glioblastoma.

PMID- 30218800
TI  - The Identification of Factors That Influence the Quality of Bypass Anastomosis
      and an Evaluation of the Usefulness of an Experimental Practical Scale in This
      Regard.
AB  - BACKGROUND: Several factors associated with interrupted and continuous suturing
      techniques affect the quality of bypass anastomosis. It is difficult to determine
      the impact of these factors during surgery. The primary objective of this study
      was to evaluate factors with the potential to influence the quality of bypass
      anastomosis using either interrupted or continuous suturing. A secondary
      objective was to evaluate the usefulness of a practical scale when comparing
      interrupted and continuous suturing techniques to improve bypass anastomosis.
      METHODS: Interrupted (n = 100) and continuous (n = 100) suturing techniques were
      used in 200 end-to-side bypasses to a depth of 3 cm and were assessed by 5
      neurosurgeons. RESULTS: Vessel closing time (P < 0.001), stitch distribution (P <
      0.001), intima-intima attachment (P < 0.001), and size of the orifice (P < 0.001)
      had a significant impact on the quality of the bypass regardless of the suturing
      technique used. The suturing technique used (interrupted or continuous) and
      positioning of the recipient vessel (vertical or horizontal) did not
      significantly influence the quality of anastomosis. Using multivariate analysis,
      the highest statistical significance with regard to bypass quality was attributed
      to the large size of the orifice and intimal attachment. CONCLUSIONS: There were
      advantages and disadvantages to both suturing techniques. The scale was a
      practical way to measure and improve performance.

PMID- 30218801
TI  - Revised Cardiac Risk Index versus ASA Status as a Predictor for Noncardiac Events
      After Posterior Lumbar Decompression.
AB  - BACKGROUND: The Revised Cardiac Risk Index (RCRI) was designed to predict risk
      for cardiac events after noncardiac surgery. However, there is a paucity of
      literature that directly addresses the relationship between RCRI and noncardiac
      outcomes after posterior lumbar decompression (PLD). The objective of this study
      is to determine the ability of RCRI to predict noncardiac adverse events after
      PLD. METHODS: The American College of Surgeons National Surgical Quality
      Improvement Program was used to identify patients undergoing PLD from 2006 to
      2014. Multivariate and receiver operating characteristic analysis was used to
      identify associations between RCRI and postoperative complications. RESULTS: A
      total of 52,066 patients met the inclusion criteria. Membership in the RCRI=1
      cohort independently predicted unplanned intubation, ventilation >48 hours,
      progressive renal insufficiency, acute renal failure, urinary tract infection
      (UTI), sepsis, septic shock, and readmission. Membership in the RCRI=2 cohort
      independently predicted for superficial surgical site infection, pneumonia,
      unplanned intubation, ventilation >48 hours, bleeding transfusion, progressive
      renal insufficiency, acute renal failure, UTI, sepsis, septic shock, and
      readmission. Membership in the RCRI=3 cohort independently predicted unplanned
      intubation (odds ratio [OR], 11.8), ventilation >48 hours (OR, 23.0), acute renal
      failure (OR, 84.5), and UTI (OR, 3.6). RCRI had a poor discriminative ability
      (DA) (area under the curve = 0.623), and American Society of Anesthesiologists
      status had a fair DA (area under the curve = 0.770) to predict a composite of
      noncardiac complications. CONCLUSIONS: RCRI was predictive of a wide range of
      noncardiac complications after PLD but had a diminished DA to predict a composite
      of any noncardiac complication than did American Society of Anesthesiologists
      score. Consideration of the RCRI as a component of preoperative surgical risk
      stratification can minimize patient morbidity and mortality after lumbar
      decompression.

PMID- 30218802
TI  - Delayed C5 Palsy After Anterior Cervical Decompression Surgery: Preoperative
      Foraminal Stenosis and Postoperative Spinal Cord Shift Increase the Risk of
      Palsy.
AB  - OBJECTIVE: Postoperative C5 palsy is a well-known complication after cervical
      decompression with either a posterior or an anterior approach. Its cause has been
      discussed more regarding the posterior approach. The main hypothesis is that
      postoperative spinal cord shift causes root traction and palsy. However, the
      pathogenesis in anterior cases has not been fully described. Therefore, the
      purpose of this study was to clarify the risk factors for C5 palsy in the
      anterior approach through our C5 palsy cases. METHODS: A total of 149 surgical
      patients with an anterior cervical lesion were treated by a specific spinal
      surgeon under consistent same treatment strategy. Of these patients, 88 who
      satisfied the evaluation criteria were enrolled. Postoperative C5 palsy was
      defined as postoperative weakness of the deltoid with or without weakness of the
      biceps brachii. Risk factors of C5 palsy were extracted from clinical
      backgrounds, surgical approaches, and radiologic findings from patients with
      palsy. RESULTS: Four sides of 3 individuals (4.6%) who underwent multiple
      corpectomy developed C5 palsy. All paralyses became evident several days after
      the surgery and recovered. Older age, multiple corpectomy, postoperative spinal
      cord shift, and foraminal stenosis of C4-5 and C5-6 were statistically extracted
      as causative factor of C5 palsy. In the patients with palsy, distortion of the
      anterior nerve root as a result of a residual vertebral spur was observed with
      anterior spinal cord shift after anterior corpectomy. CONCLUSIONS: Multiple
      corpectomy for patients with longer anterior lesions and locally developed
      kyphosis is related to a larger postoperative cord shift, which can cause the
      occurrence of C5 palsy. Moreover, C4-5 or C5-6 foraminal stenosis can accelerate
      tethering of the C5 or C6 nerve root. Older patients undergoing multiple
      corpectomy are susceptible to these risks of palsy. Appropriate patient selection
      and sufficient additional foraminotomy should be considered for extensive
      anterior lesions and locally developed kyphosis to avoid postoperative C5 palsy.

PMID- 30218803
TI  - Establishment of a Nomogram-Based Model for Predicting the Prognostic Value of
      Inflammatory Biomarkers and Preoperative D-Dimer Level in Spinal Ewing's Sarcoma
      Family Tumors: A Retrospective Study of 83 Patients.
AB  - BACKGROUND: Ewing's sarcoma family tumors (ESFTs) are the second most common
      malignancy in children and adolescents. The purpose of the present retrospective
      study was to evaluate the prognostic role of inflammatory biomarkers and
      preoperative D-dimer levels in patients with spinal ESFTs. METHODS: The
      neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte
      ratio, albumin/globulin ratio, C-reactive protein/albumin ratio (CAR),
      preoperative D-dimer level, and clinical parameters were evaluated and analyzed.
      Univariate and multivariate analyses for disease-free survival (DFS) and overall
      survival (OS) were performed using the log-rank test and Cox regression analysis,
      respectively. The DFS and OS rates were calculated using the Kaplan-Meier method.
      Nomograms were established to predict DFS and OS quantitatively. RESULTS: The
      optimal cutoff values for D-dimer, neutrophil/lymphocyte ratio,
      platelet/lymphocyte ratio, lymphocyte/monocyte ratio, CAR, and albumin/globulin
      ratio were 0.3, 3.2, 168, 2.2, 1.5, and 1.4, respectively. The patients were
      stratified into 2 groups according to the cutoff values. Multivariate analysis
      revealed that age, resection mode, and D-dimer level were favorable prognostic
      factors for DFS and OS (P < 0.05). Metastasis and CAR <1.5 were significantly
      associated with OS (P < 0.05). Nomograms with all significant factors were
      established to predict DFS and OS. CONCLUSIONS: Our results have indicated that
      the preoperative D-dimer level is an effective prognostic factor with
      discriminatory ability for DFS and OS, superior to other indicators. Also, CAR
      was favorable prognostic factor for OS. Nomograms of DFS and OS can be
      recommended as practical models to evaluate the prognosis for patients with
      spinal ESFTs.

PMID- 30218804
TI  - Academic Genealogy of Neurosurgery via Department Chair.
AB  - BACKGROUND: An academic genealogy describes mentoring relationships in an
      academic discipline. In this study, we outline an academic genealogy of
      neurosurgery department chairs in the United States beginning with the founding
      members of the field. METHODS: The biographic information provided by the Society
      for Neurological Surgery provided the basis for our genealogy. We also performed
      a literature review with PubMed using the term neurosurgery department history.
      Our data was manually uploaded to an online database called Academic Tree. Within
      this platform, mentor and trainee relationships were indicated to produce an
      academic genealogy. RESULTS: Our search yielded a total of 377 chairs and 368
      mentoring relationships across 98 neurosurgery departments. The largest family
      tree in our academic genealogy was that of Harvey Cushing, with 177 department
      chairs. Harvey Cushing was also the individual who trained the most number of
      department chairs (22). The institution that trained the most department chairs
      was Brigham and Women's Hospital (26). Only 23.6% of department chairs completed
      residency training at the same institution where they became chair. CONCLUSIONS:
      The academic genealogy in this study allows for any neurosurgeon trained in the
      United States to put his or her training into historical context. It also
      provides a reference for bibliographic research to quantitatively describe the
      influence of individuals and institutions on the field.

PMID- 30218805
TI  - Treatment of Unruptured Brain Arteriovenous Malformations: A Single-Center
      Experience of 86 Patients and a Critique of the A Randomized Trial of Unruptured
      Brain Arteriovenous Malformations (ARUBA) Trial.
AB  - OBJECTIVE: The A Randomized Trial of Unruptured Brain Arteriovenous Malformations
      (ARUBA) trial has received fierce criticism, including considerable selection
      bias, poor generalizability, questionable clinical practices (only 15.8%
      underwent surgical resection, the gold standard for arteriovenous malformation
      [AVM] treatment), and short follow-up (33 months) for a disease process that
      carries a life-long risk. In this study, we sought to present our own experience
      treating unruptured brain AVMs to provide supporting evidence of the ARUBA trial
      criticism. METHODS: All cases of treated brain AVMs from 2004 to 2017 at our
      institution were retrospectively reviewed and included in the analysis if they
      met ARUBA trial inclusion criteria. The primary outcome was symptomatic stroke or
      death. Secondary outcomes included AVM obliteration, long-term clinical
      impairment (modified Rankin Scale score >1), and new major or minor postoperative
      deficit. RESULTS: Of the 245 reviewed cases, 86 met the ARUBA trial criteria.
      Treatment included microsurgical resection alone (2.3%), preoperative
      embolization followed by microsurgical resection (62.8%), stereotactic
      radiosurgery alone (10.5%), embolization followed by stereotactic radiosurgery
      (15.1%), and embolization alone (9.3%). The primary outcome was met in 8.3%, new
      perioperative major and minor complications occurred in 5.8% and 12.8%, and long
      term clinical impairment in 4.5%. AVM obliteration was observed in 92.4% overall
      and in 100% of patients who underwent surgical resection. CONCLUSIONS: The
      criticism of the ARUBA trial is warranted, as our study found that treatment of
      unruptured brain AVMs has an acceptable safety profile when approached in a
      multidisciplinary manner at an experienced institution, using surgical resection
      as the primary treatment modality when applicable.

PMID- 30218806
TI  - The complexities and contradictions in participatory research with vulnerable
      children and young people: A qualitative systematic review.
AB  - Participatory research carried out by or with children, has become a well
      established and valuable part of the research landscape investigating children's
      lives, views and needs. So too has a critical agenda about its ethical
      implications and methodological complexities. One criticism is that the
      involvement of children who may be considered 'vulnerable' or 'marginalised' has
      been slower to take root within mainstream participatory practice. This means
      that there has been less focus on how groups such as disabled children or
      children affected by abuse or neglect can shape and challenge adult-dominated
      types of knowledge and decision-making that are likely to affect them. This
      article reports on the findings of a qualitative systematic literature review of
      thirteen contemporary papers. The review was undertaken by a UK team in 2017. The
      included articles explored some core ethical and methodological issues involved
      in carrying out participatory research with vulnerable children and young people.
      It reports on three themes: 1) The extent to which participatory spaces could
      recalibrate opportunities and attention given to marginalised and silenced
      groups; 2) The ways in which these children and young people could develop skills
      and exercise political and moral agency through participatory activity, and, 3)
      How to facilitate meaningful engagement with individuals and groups and reconcile
      this with a critical appreciation of the important but limited nature of research
      as means of political and social change. The review provides a unique,
      contemporary analysis of participatory research with vulnerable children,
      illuminating in particular its conceptual complexities and contradictions,
      particularly regarding power, empowerment and voice. Its overall utility and
      interest is augmented by the disciplinary and geographical breadth of the
      included articles, rendering it relevant to many contexts and countries.

PMID- 30218807
TI  - Home video telemetry in children: A comparison to inpatient video telemetry.
AB  - PURPOSE: Home Video Telemetry (HVT) combines ambulatory EEG with simultaneous
      video recording. No previous reports have compared HVT and inpatient video
      telemetry (IVT) in a purely paediatric population. This study compares HVT and
      IVT in this group in terms of diagnostic efficacy, recording quality and
      acceptability to parents/carers. METHODS: 33 HVT and 29 IVT patients aged 1-17
      years were included. Information regarding patient demographics, ictal capture,
      diagnostic utility, recording quality (e.g. video clarity, EEG artefacts) and
      parent/carer preferences was documented. Difficulties using HVT equipment were
      recorded. RESULTS: 62% of IVT patients and 64% of HVT patients had typical
      attacks during the recording. 59% of IVT and 70% of HVT recordings were
      considered to have answered the referral question. Study quality was similar in
      both groups. In HVT studies the rate of equipment difficulties was 52%; problems
      included camera positioning and failure to turn on the infrared button at night.
      Diagnostic information was lost in 15% of patients. 76% of parents/carers of HVT
      patients would choose this investigation again. CONCLUSIONS: The diagnostic
      efficacy and study quality of HVT and IVT are similar in paediatric patients. HVT
      is acceptable to most parents/carers. User error may compromise the investigation
      in a minority of cases but did not impact on diagnostic utility. Adoption of HVT
      investigation could provide an accessible and economic alternative to IVT.

PMID- 30218809
TI  - Bu Yang Huan Wu decoction prevents reperfusion injury following ischemic stroke
      in rats via inhibition of HIF-1 alpha, VEGF and promotion beta-ENaC expression.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bu Yang Huan Wu Decoction (BYHW) is a famous
      traditional Chinese medicine (TCM) formula used in China for the treatment of
      cerebral ischemic stroke. But the protective effects and underlining mechanisms
      of BYHW remain unclear. AIM OF THE STUDY: This study was designed to investigate
      the protective effects and underlining signaling mechanisms of BYHW on brain
      tissues in a rat model of cerebral ischemic reperfusion (I/R) injury. MATERIALS
      AND METHODS: Liquid chromatography was used to verify the composition of BYHW.
      The cerebral edema and infarct volume were measured by magnetic resonance imaging
      (MRI). The morphology and ultrastructure of ischemic penumbra brain tissues were
      observed by hematoxylin-eosin (HE) and transmission electron microscopy (TEM).
      The expression levels of HIF-1 alpha, VEGF and beta-ENaC were tested using
      immunohistochemistry technique, western blot and quantitative PCR analysis,
      respectively. RESULTS: Administration of BYHW significantly decreased cerebral
      edema, rat neurological function scores, reduced brain infarct volume. At the
      same time, BYHW had protective effect on the blood-brain barrier (BBB), which
      improved the morphology and ultrastructure of ischemic penumbra brain tissues.
      BYHW treatment significantly decreased the protein and mRNA levels of HIF-1 alpha
      and VEGF compared with the model treatment. In addition, BYHW treatment
      significantly up-regulated the protein and mRNA levels of beta-ENaC. CONCLUSIONS:
      BYHW protected against cerebral I/R injury in MCAO rats through inhibiting the
      activation of the HIF-1 alpha /VEGF pathway and stabilizing ion channel of beta
      ENaC in brain, indicating that BYHW shows potential for stroke treatment in acute
      stage.

PMID- 30218808
TI  - Seizure-like episodes and EEG abnormalities in patients with long QT syndrome.
AB  - PURPOSE: The congenital long QT-syndrome (cLQTS) is characterized by ventricular
      arrhythmias, syncope and sudden cardiac death. Many LQTS genes are also expressed
      in the brain and emerging evidence suggest that cardiac channelopathies can also
      cause epilepsy. The aim of the study is to explore evidence of epilepsy and/or
      EEG abnormalities in a cohort with a genotyped diagnosis of LQT1 or LQT2.
      METHODS: Adult patients were randomly selected from the outpatient clinic and a
      random sample of healthy controls were recruited from the general population.
      Ictal semiology was explored in symptomatic patients. A 1 h 64-channel awake EEG
      was performed and analyzed by visual assessment. Brain connectivity was
      quantified by Directed Transfer Function (DTF) from the current source density
      estimate within the theta band (4-7 Hz). RESULTS: Fifteen patients with LQT1, 20
      with LQT2 and 20 controls were included. Seventy-one % of the patients reported
      loss of consciousness (LOC); 44% in combination with convulsions. EEG was
      abnormal in 34% of patients and 10% of controls (p < 0.05). Two patients had
      epileptiform or sharp activity. The fronto-parietal DTF connectivity was
      significantly altered in patients compared to controls (LQT1 p = 2.2 * 10-6, LQT2
      p = 0.044). CONCLUSION: Seizure-like episodes and EEG abnormalities were common
      in our cohort with cLQTS patients. However, we could not find firm evidence of
      epilepsy. Our findings reinforce the notion that cLQTS is a cardiocerebral
      channelopathy. Correct classification of seizures may be challenging to the
      clinician, but of vital importance for patients.

PMID- 30218810
TI  - The immunostimulatory effects and chemical characteristics of heated honey.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), honey has
      been used as an additive in the heat-processing of herbal medicines to enhance
      their immunostimulatory activities. AIM OF THE STUDY: We investigated the
      immunostimulatory activity of heated honey in vitro and in vivo. MATERIALS AND
      METHODS: For the in vitro study, we compared the differences among the inducible
      effects of honey subjected to various heating conditions on granulocyte colony
      stimulating factor (G-CSF) secretion from the cultured enterocytes and
      investigated the active ingredient. For the in vivo study, we conducted a
      survival test of mice infected by Streptococcus pyogenes with and without oral
      administration of heated honey. RESULTS: We found that heating the honey induced
      the appearance of G-CSF secretions from the cultured enterocytes, and that this
      appearance depended on the heating temperature and time. No G-CSF secretions
      appeared when honey was not heated. Mice infected with Streptococcus pyogenes
      that were fed heated honey revealed prolonged survival. The active ingredient in
      heated honey was a high-molecular compound with about 730 kDa. When this compound
      was hydrolyzed, galactose, glucose, rhamnose, alpha-ribofuranose beta
      ribofuranose 1,5':1',5-dianhydride, and 5-hydroxymethylfurfural were generated.
      CONCLUSIONS: Heated honey reveals immunostimulatory activity both in vitro and in
      vivo. These results support the scientific evidences of the TCM theory.

PMID- 30218811
TI  - Effects of Parkia biglobosa aqueous seed extract on some biochemical,
      haematological and histopathological parameters in streptozotocin induced
      diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Parkia biglobosa seeds are used to treat diabetes
      and complications hence this study. AIM: This study investigated the effects of
      Parkia biglobosa aqueous seed extract on some biochemical, haematological and
      histopathological indices in streptozotocin-induced diabetic rats. MATERIALS AND
      METHODS: Wistar rats of either sex (180-300 g) were fasted overnight and diabetes
      mellitus induced using streptozotocin 40 mg/kg IP. Diabetes mellitus (fasting
      blood glucose >= 200 mg/dl) was confirmed 48 h later. The rats were randomly
      grouped into six groups (n = 5): Group 1 (diabetic untreated control), group 2
      (Parkia biglobosa 200 mg/kg), group 3 (Parkia biglobosa 400 mg/kg). group 4
      (Parkia biglobosa 800 mg/kg), group 5 (glibenclamide 5 mg/kg as standard drug
      control) and group 6 (normoglycaemic control). They were treated daily. Acute
      toxicity study and phytochemical screening were also performed. Fourteen days
      later, they were sacrificed under chloroform anaesthesia. Vital organs (kidneys,
      liver and pancreas) and blood samples were obtained for histopathological,
      biochemical and haematological analysis. RESULTS: Parkia biglobosa aqueous seed
      extract at the various doses caused significant (P < 0.05) elevations in red
      blood cell parameters in comparison to the diabetic control. The mean cell volume
      did not differ significantly from the diabetic control while 200 mg/kg and 400
      mg/kg doses of the extract did not significantly modify the HCT levels. Treatment
      with Parkia biglobosa significantly (P < 0.05) lowered white blood cell and
      platelet counts in comparison to the diabetic control. Liver enzymes and total
      bilirubin levels were significantly (P < 0.05) reduced while total protein
      increased in the treated diabetic rats in comparison to controls. Treatment with
      Parkia biglobosa extract significantly (P < 0.05) increased bicarbonate and
      sodium ion levels while decreasing potassium ion levels. Chloride levels were not
      significantly different from the diabetic control. CONCLUSION: These data suggest
      that Parkia biglobosa ameliorates biochemical, haematological and
      histopathological changes associated with diabetes mellitus.

PMID- 30218812
TI  - An ethanol extract of the rhizome of Atractylodes chinensis exerts anti-gastritis
      activities and inhibits Akt/NF-kappaB signaling.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Atractylodes chinensis (DC.) kodiz
      (Compositae) has traditionally been used to treat inflammatory disorders such as
      arthritis and stomach ache, but scanted report has been issued on its anti
      inflammatory mechanisms. AIM OF THE STUDY: Here, we investigated the anti
      gastritis activities and explored the mechanism of action of an ethanolic extract
      of the herb (Ac-EE). MATERIALS AND METHODS: Ac-EE was prepared with 95% ethanol.
      To determine its in vivo effects, we employed an HCl/EtOH-induced gastritis rat
      model. We used a lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage model
      for in vitro assays. Griess and MTT assays were used to measure nitric oxide (NO)
      production and cell viability, respectively. We used real-time PCR to determine
      mRNA levels. To measure prostaglandin E2 (PGE2) production we used a PGE2 EIA
      kit. To estimate protein levels and enzyme activities, we employed
      immunoblotting. Luciferase assays were used to examine nuclear transcription
      factor (NF)-kappaB activities. RESULTS: Intragastric administration of Ac-EE (30
      mg/kg) ameliorated HCl/EtOH-induced stomach tissue damages in SD rats. Ac-EE
      inhibited the levels of NO and PGE2, down regulated mRNA and protein levels of
      inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Ac-EE suppressed the
      nuclear level of NF-kappaB (p50), and inhibited NF-kappaB luciferase activity.
      The Phosphorylation of Akt and IkappaBalpha was also inhibited by Ac-EE both in
      vivo and in vitro. CONCLUSION: Ac-EE treatment exerts an anti-gastritis effect in
      rats. Inhibition of the Akt/IkappaBalpha/NF-kappaB signaling pathway is
      associated with this effect, providing a pharmacological basis for the clinical
      application of the rhizome of A. chinensis in the treatment of inflammatory
      diseases.

PMID- 30218813
TI  - Fabiana imbricata Ruiz et Pav. (Solanaceae), a review of an important Patagonian
      medicinal plant.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Fabiana imbricata (Solanaceae) is a Patagonian
      medicinal plant with a long tradition of use. The aim of this review is to
      provide an integrative overview of the traditional uses, chemistry, bioactivity
      and chemical profiling of the crude drug. MATERIALS AND METHODS: The information
      was collected from scientific databases searching with the keywords Fabiana
      imbricata, Fabiana species, Fabiana (Solanaceae) and includes local literature
      and books. RESULTS: The indications of use reported in literature show little
      variation from the data published as early as 1889. The chemical studies showed a
      rich diversity in metabolites including phenolics, coumarins, flavonoids,
      phenylpropanoids, terpenes, alkaloids and sugars. Bioactivity studies supported
      the traditional use as diuretic and also the potential of the crude drug as a
      gastroprotective agent. The plant can be used as a source of compounds with
      effect on gastric ulcers and shows enzyme inhibitory activity. While the
      germination rate of the plant is very low, protocols were developed for the rapid
      in vitro propagation of the species. The toxicity of the crude drug extracts was
      low and did not show clastogenic effect in human lymphocytes. Further research is
      needed to disclose the potential of the F. imbricata sesquiterpenes on other
      relevant biological targets.

PMID- 30218814
TI  - Spatiotemporal patterns and determinants of dengue at county level in China from
      2005-2017.
AB  - OBJECTIVE: To identify the high risk spatiotemporal clusters of dengue cases and
      explore the associated risk factors. METHODS: Monthly indigenous dengue cases in
      2005-2017 were aggregated at county level. Spatiotemporal cluster analysis was
      used to explore dengue distribution features using SaTScan9.4.4 and Arcgis10.3.0.
      In addition, the influential factors and potential high risk areas of dengue
      outbreaks were analyzed using ecological niche models in Maxent 3.3.1 software.
      RESULTS: We found a heterogeneous spatial and temporal distribution pattern of
      dengue cases. The identified high risk region in the primary cluster covered 13
      counties in Guangdong Province and in the secondary clusters included 14 counties
      in Yunnan Province. Additionally, there was a nonlinear association between
      meteorological and environmental factors and dengue outbreaks, with 8.5%-57.1%,
      6.7%-38.3% and 3.2%-40.4% contribution from annual average minimum temperature,
      land cover and annual average precipitation, respectively. CONCLUSIONS: The high
      risk areas of dengue outbreaks mainly are located in Guangdong and Yunnan
      Provinces, which are significantly shaped by environmental and meteorological
      factors, such as temperature, precipitation and land cover.

PMID- 30218815
TI  - A large cardiac hydatid cyst in the interventricular septum: A case report.
AB  - Isolated cardiac location is an uncommon presentation of echinococcosis (0.5-2%),
      and involvement of the interventricular septum is even rarer. It may lead to
      various complications because of rupture and embolization. We report the case of
      a 26 - year- old man who was diagnosed to have a large inter-ventricular hydatid
      cyst complicated by both cerebral and coronary embolism. Presentation, management
      and follow-up of the patient is discussed. This case is of particular interest
      because of the rarity of septal localization of a hydatid cyst, and the conflict
      between the severity of the complications that occurred and the absence of
      correlated symptoms.

PMID- 30218816
TI  - Respiratory infection due to direct contact with rabbit-skin powder contaminated
      by vaccinia virus.
AB  - Vaccinia virus infection was diagnosed in five male workers directly exposed to
      rabbit-skin powder contaminated by vaccinia virus via skin contact and
      inhalation. Four of the workers had been vaccinated against smallpox. Their
      clinical symptoms were severe, especially in the lungs; however, all symptoms
      improved after treatment.

PMID- 30218817
TI  - Assessment of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry for identification and biotyping of the pathogenic oomycete Pythium
      insidiosum.
AB  - OBJECTIVE: Pythiosis is a life-threatening infectious disease caused by the
      oomycete Pythium insidiosum. The disease has been increasingly reported
      worldwide. Most patients with pythiosis undergo surgical removal of an infected
      organ. Early diagnosis contributes to better prognosis of pythiosis patients.
      Here, we assessed the matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (MALDI-TOF MS) for identification and biotyping of P.
      insidiosum. METHODS: A comprehensive set of mass spectra of P. insidiosum was
      generated to evaluate MALDI-TOF MS for identification and biotyping of P.
      insidiosum. RESULTS: MALDI-TOF MS accurately identified all 13 P. insidiosum
      strains tested, at the species level. Mass spectra of P. insidiosum did not match
      any other microorganisms, including fungi (i.e., Aspergillus species, Fusarium
      species, and fungal species of the class Zygomycetes), which have similar
      microscopic morphologies with this oomycete. MALDI-TOF MS- and rDNA sequence
      based biotyping methods consistently classified P. insidiosum into three groups:
      Clade-I (American strains), II (Asian and Australian strains), and III (mostly
      Thai strains). CONCLUSIONS: MALDI-TOF MS has been successfully used for
      identification and biotyping of P. insidiosum. The obtained mass spectral
      database allows clinical microbiology laboratories, well-equipped with a MALDI
      TOF mass spectrometer, to conveniently identify P. insidiosum, without requiring
      any pathogen-specific reagents (i.e., antigen, antibody or primers).

PMID- 30218820
TI  - The use of splenic artery embolization to maintain adequate hepatic arterial
      inflow after hepatic artery thrombosis in a split liver transplant recipient.
AB  - INTRODUCTION: Split liver transplant is gaining increasing use in the current
      environment of growing organ shortage. It is associated with a higher risk of
      complications, owing to its complexity and technical challenges. Splenic artery
      steal syndrome, is a complication that can occur following liver transplant and
      cause inadequate hepatic arterial inflow, hepatic artery thrombosis and graft
      loss. We report a successful management of hepatic artery thrombosis and splenic
      artery steal syndrome after a split liver transplant by surgical thrombectomy
      followed by angiography and splenic artery embolization. CASE: 60-year old
      female, with liver cirrhosis, who underwent a deceased donor right lobe
      orthotopic liver transplant. The procedure was complicated by hepatic artery
      thrombosis, requiring re-exploration. However, despite anastomotic revision the
      patient had poor hepatic arterial inflow. Both angiography and ultrasonography
      demonstrated splenic artery steal syndrome. This was successfully managed by
      splenic artery embolization with improved hepatic artery flow on ultrasonography
      and angiography. CONCLUSION: Splenic artery steal syndrome is a rare complication
      that can occur after a liver transplant. Experience with this phenomenon is
      limited in split liver transplantation.We demonstrated successful early
      management of splenic artery steal syndrome with coil embolization in a split
      liver transplant preventing further morbidity and graft loss.

PMID- 30218819
TI  - Clear cell variant squamous cell carcinoma of temporal bone: Case report and
      literature review.
AB  - INTRODUCTION: Squamous cell carcinoma (SCC) of the temporal bone is a rare
      malignancy. Clear cell SCC is a rare variant of SCC of temporal bone in which no
      clear risk factor has been suggested as possible etiology. Otalgia, otorrhea, and
      hearing loss are the usual presenting symptoms of SCC of the temporal bone.
      PRESENTATION OF CASE: This is a case is of a 62-year-old female who presented
      with a 6 months' history of experiencing intermittent left hearing disturbance,
      loss of balance, persistent left tinnitus, left otalgia radiating to the lateral
      neck and post auricular swelling. Histology showed clear cell variant, well
      differentiated SCC. The patient's tumor was found to be non-resectable due to the
      extensive invasion. The patient was referred for palliative therapy by medical
      and radiation oncology, however, the patient couldn't tolerate it. One month
      later she passed away. DISCUSSION: SCC of the temporal bone is a challenging
      clinical entity. It is diagnosed mainly by clinical and radiological assessment,
      and deep biopsies are used to confirm the diagnosis. Temporal bone SCC is usually
      diagnosed late due to delayed presentation. This case of temporal bone SCC was
      aggressive in nature and presentation. The presentation was different from the
      known triad of symptoms of temporal bone SCC which is offensive otorrhea, pain,
      and bleeding. CONCLUSION: This case showed a very destructive and bizarre
      clinical presentation but more report of cases is needed to have a better
      characterization of the clinical presentation and prognosis of this variant of
      SCC of temporal bone.

PMID- 30218821
TI  - A rare presentation of IgG4 related disease as a gastric antral lesion: Case
      report and review of the literature.
AB  - INTRODUCTION: Immunoglobulin G4 related disease is a recently recognized systemic
      fibro-inflammatory disorder affecting virtually every organ in the body,
      characterized by lympho-plasmacytic dense infiltrates rich in IgG4 positive
      plasmacytes along with storiform fibrosis, inconstantly associated with elevated
      serum IgG4 levels. Few cases of Immunoglobulin G4 related disease occurring
      solely in the stomach have been published. PRESENTATION OF CASE: We herein
      present a rare case of a 57 year old male patient presenting with an incidentally
      discovered asymptomatic pre-pyloric submucosal gastric lesion confused with a
      gastro-intestinal stromal tumor with failed endoscopic biopsy attempts due to
      tumor mobility. The patient underwent wedge resection of the lesion which was
      diagnosed postoperatively as Immunoglobulin G4 related disease. DISCUSSION:
      Immunoglobulin G4 related disease presenting as a solitary lesion in the stomach
      is a very rare condition. It should be kept in the differential diagnosis of a
      submucosal mass or polyp. The treatment is medical with systemic steroid therapy.
      CONCLUSION: Obtaining a tissue biopsy is of extreme importance to avoid
      unnecessary surgery.

PMID- 30218822
TI  - Myofibroblastic infiltration of the bowel: A case report and literature review.
AB  - INTRODUCTION: Inflammatory myofibroblastic tumours (IMTs), are uncommon tumours
      which can act with malignant potential. The management of these tumours can be
      extremely problematic but are often referred to surgical multi-disciplinary team
      meetings with the intention of surgical and oncological management (Chaudhary
      [1]). CASE REPORT: A 69-year-old gentleman was admitted with a 2-day history of
      abdominal pain and vomiting, and a 4-day history of absolute constipation. CT
      Abdomen Pelvis demonstrated distended loops of small bowel with pronounced fluid
      levels but no transition point. Intra-operative findings showed a right ileocolic
      mass adherent to the pelvic side wall and omental caking. Biopsies showed a
      florid myofibroblastic reaction, not a malignant process. CONCLUSION: IMTS are
      aggressive lesions but metastases is rare. Abdominal IMTS are difficult to
      diagnose and manage as they are often initially mistaken for lymphoma or
      peritoneal metastases. The therapy of choice is surgical resection of the tumour
      (Firat et al. [3]).

PMID- 30218818
TI  - Putting patients at the center of kidney care transitions: PREPARE NOW, a cluster
      randomized controlled trial.
AB  - : Care for patients transitioning from chronic kidney disease to kidney failure
      often falls short of meeting patients' needs. The PREPARE NOW study is a cluster
      randomized controlled trial studying the effectiveness of a pragmatic health
      system intervention, 'Patient Centered Kidney Transition Care,' a multi-component
      health system intervention designed to improve patients' preparation for kidney
      failure treatment. Patient-Centered Kidney Transition Care provides a suite of
      new electronic health information tools (including a disease registry and risk
      prediction tools) to help providers recognize patients in need of Kidney
      Transitions Care and focus their attention on patients' values and treatment
      preferences. Patient-Centered Kidney Transition Care also adds a 'Kidney
      Transitions Specialist' to the nephrology health care team to facilitate
      patients' self-management empowerment, shared-decision making, psychosocial
      support, care navigation, and health care team communication. The PREPARE NOW
      study is conducted among eight [8] outpatient nephrology clinics at Geisinger, a
      large integrated health system in rural Pennsylvania. Four randomly selected
      nephrology clinics employ the Patient Centered Kidney Transitions Care
      intervention while four clinics employ usual nephrology care. To assess
      intervention effectiveness, patient reported, biomedical, and health system
      outcomes are collected annually over a period of 36 months via telephone
      questionnaires and electronic health records. The PREPARE NOW Study may provide
      needed evidence on the effectiveness of patient-centered health system
      interventions to improve nephrology patients' experiences, capabilities, and
      clinical outcomes, and it will guide the implementation of similar interventions
      elsewhere. TRIAL REGISTRATION: NCT02722382.

PMID- 30218823
TI  - Molecular characterization and expression of TLR7 and TLR8 in barbel chub
      (Squaliobarbus curriculus): Responses to stimulation of grass carp reovirus and
      lipopolysaccharide.
AB  - The barbel chub (Squaliobarbus curriculus) is a kind of small size commercial
      fish species that is widely spread in Asia and has shown significant resistance
      to disease. In this study, the full-length cDNA sequences of Toll-like receptor
      (TLR) 7 and 8 from S. curriculus, designated as ScTLR7 and ScTLR8, were cloned,
      and their differences in the structure and the responses to the grass carp (GCRV)
      infection and lipopolysaccharide stimulation were investigated. The full-length
      3715 base pair (bp) cDNA of ScTLR7 contained a complete open reading frame of
      3162 bp and encoded a putative polypeptide of 1053 amino acid residues. The full
      length 4624 base pair (bp) cDNA of ScTLR8 contained a complete open reading frame
      of 3072 bp and encoded a putative polypeptide of 1023 amino acid residues. ScTLR7
      and ScTLR8 consisted of N-terminal signal peptide, leucine-rich repeats (LRRs),
      and Toll/IL-1 Receptors domain. LRR motifs of ScTLR7 and ScTLR8 bend into
      horseshoe-like solenoid structure, while the number of LRRs between the two genes
      is different. Phylogenetic analysis showed that both the ScTLR7 and ScTLR8 were
      closely clustered with Ctenopharyngodon idellus and Megalobrama amblycephala.
      Quantitative real-time polymerase chain reaction analysis showed that the
      expression levels of ScTLR7 in S. curriculus were most abundant in the brain
      followed by the spleen and heart, and the lowest in the intestine. The highest
      expression level of ScTLR8 was observed in spleen and the lowest in the liver.
      After LPS stimulation, the relative expression levels of both ScTLR7 and ScTLR8
      exhibited an overall trend of up-regulation. The expression levels of type I-IFN
      showed an overall trend of down-regulation at time points of 12, 24, 72 and 168 h
      compared to that of 6 h after LPS stimulation. Compared to 6 h post GCRV
      infection, the transcription level of ScTLR7 was up-regulated from 12 to 168 h,
      and transcription levels of ScTLR8, MyD88, and type I-IFN were firstly up
      regulated from 12 to 72 h, and then down-regulated from 72 to 168 h. Correlation
      analysis showed that expression level of ScTLR7 in the spleen was significantly
      positively correlated with that of MyD88 (Pearson correlation coefficient: 0.909,
      P: 0.033), and a significantly positive correlation was also observed between
      expression levels of MyD88 and type I IFN (Pearson correlation coefficient:
      0.962, P: 0.009), after GCRV stimulation. These results indicate that ScTLR7 and
      ScTLR8 may play important roles in the responses to the grass carp (GCRV)
      infection and lipopolysaccharide stimulation and trigger different downstream
      immune signal pathways.

PMID- 30218824
TI  - Effects of aminomethylphosphonic acid, the main breakdown product of glyphosate,
      on cellular and biochemical parameters of the mussel Mytilus galloprovincialis.
AB  - The effects of the breakdown products of herbicides on aquatic species are
      largely unknown. In a recent study, we evaluated the effects of glyphosate on the
      mussel Mytilus galloprovincialis. This study was designed to evaluate for the
      first time the impact of aminomethylphosphonic acid (AMPA) - the main breakdown
      product of glyphosate - on cellular and biochemical parameters of the mussel
      Mytilus galloprovincialis. Bivalves were exposed for 7, 14 and 21 days to 1, 10
      and 100 MUg/L of AMPA and various biomarkers were measured in haemolymph (total
      haemocyte counts, haemocyte diameter and volume, haemolymph pH, haemocyte
      proliferation, haemolymph lactate dehydrogenase activity, haemocyte lysate
      lysozyme and acid phosphatase activities), as well as in gills and digestive
      gland (superoxide dismutase, catalase, glutathione S-transferase and
      acetylcholinesterase activities). AMPA concentrations in seawater samples from
      the experimental tanks were also measured in order to correlate the biomarker
      responses of mussels with their exposure to the actual concentrations of AMPA.
      The MANOVA analysis demonstrated that the experimental variables considered
      (exposure dose, exposure duration, and their interaction) affected significantly
      biomarker responses. Nevertheless, the two-way ANOVA analysis revealed
      significant effects of AMPA on most of the biomarkers measured. The overall
      results of this study demonstrated that AMPA can affect cellular and biochemical
      parameters in mussels, similarly to glyphosate.

PMID- 30218825
TI  - Determination of intestinal permeability using in situ perfusion model in rats:
      Challenges and advantages to BCS classification applied to digoxin.
AB  - The purpose of this work was to describe the closed loop in situ perfusion method
      in rats and to compare the difficulties and advantages with other methods
      proposed by regulatory agencies for BCS classification and finally to illustrate
      its application to evaluate the permeability of digoxin at relevant clinical
      concentrations. Digoxin was evaluated at two concentration levels: 1.0 MUg/ml
      (with and without sodium azide 65.0 MUg/ml) and 6.0 MUg/ml. These concentrations
      correspond to the ratio of the highest dose strength (0.25 mg) and the highest
      single dose administered (1.5 mg) and the 250 ml of water. In situ closed loop
      perfusion studies in rats were performed in the whole small intestine and also in
      duodenum, jejunum and ileum segments to evaluate the relevance of P-gp secretion
      in the overall permeability. A kinetic modelling approach involving passive
      permeation and efflux transport mechanism allowed the estimation of the passive
      diffusional component and the Michaelis-menten parameters. The estimated Km value
      demonstrated that at clinical luminal concentrations the efflux process is not
      saturated and then it could be inhibited by other drugs, excipients or food
      components leading to the already reported clinical drug-drug and drug-food
      interations. The present data confirms from a mechanistic point of view these
      interactions.

PMID- 30218826
TI  - Reconstituted spray-dried phenytoin-loaded nanocapsules improve the in vivo
      phenytoin anticonvulsant effect and the survival time in mice.
AB  - This study evaluated the in vivo anticonvulsant effect of a spray-dried powder
      for reconstitution containing phenytoin-loaded lipid-core nanocapsules. The
      effect of chitosan coating on redispersibility, gastrointestinal stability, and
      drug release from nanoparticles was evaluated during the development of the
      powders. Maltodextrin was used as adjuvant in the spray-drying process. Chitosan
      coating played an important role in redispersibility, and large particles (>100
      MUm) were obtained using the highest concentration of solids in the feed.
      However, after aqueous redispersion, volume-based particle size was reduced to
      about 1 um. The release of nanoparticles from the surface of the spherical
      microagglomerates (roundness index = 0.75) was confirmed by SEM analysis. Powders
      reconstituted in water recovered partially the nanometric properties of the
      original suspensions and were stable for 24 h. Phenytoin-loaded chitosan-coated
      nanocapsules and their redispersed powders have good gastrointestinal stability,
      and are able to control drug release in simulated gastric and intestinal fluids.
      Besides that, the reconstituted powder containing chitosan-coated nanocapsules
      exhibited improved anticonvulsant activity against seizures induced by
      pilocarpine in mice, compared to the non-encapsulated drug, representing an
      important approach in anticonvulsant treatments for children and adults.

PMID- 30218827
TI  - Potential role of stromal collagen in cystine crystallization in cystinosis
      patients.
AB  - Cystinosis is a genetic disease that leads to the accumulation of intracellular
      cystine crystals in all organs including cornea due to the loss of cystine efflux
      transporters in the lysosome of the cells. While the mechanism for formation of
      intracellular cystine is well understood for most organs, it does not explain
      many observations for crystal accumulation in the cornea of cystinosis patients.
      First, the crystals in cornea are extracellular and needle-like with several
      hundred microns length which is in sharp contrast with the rectangular or
      hexagonal crystals found throughout other organs. Second, these crystals are
      arranged parallel to the stromal collagen, which is a unique to the cornea.
      Third, crystal growth in the cornea reaches a saturation point after where no
      further crystallization occurs. We propose a hypothesis supported by in vitro and
      ex vivo data to explain these observations. We hypothesize that the stroma
      crystals form extracellularly due to the ionic interactions between the cystine
      diffusing into the eye and collagen fibrils present in the stroma. We examine
      cystine crystal growth both with in vitro polymer solutions and ex vivo in rabbit
      cadaver eyes to show that negatively charged polymers lead to the formation of
      more cystine precipitation in aqueous solution and that needle-like cystine
      crystal formation can be observed only in presence of certain polyelectrolytes
      including collagen. This proposed mechanism explains many of the yet unanswered
      questions but it needs further support from in vivo studies. The improved
      understanding could lead to improved treatment of corneal cystinosis.

PMID- 30218828
TI  - Defining Types and Determining Risk Factors for Vascular Surgery Readmissions.
AB  - BACKGROUND: Vascular surgery patients typically have numerous comorbidities,
      which puts them at higher risk for postoperative readmissions. This study aims to
      investigate the risk factors for and appropriately categorize the various types
      of vascular surgery readmissions. METHODS: Nine hundred seventy-two patients were
      retrospectively reviewed. Readmissions were classified into 3 separate groups:
      readmissions that occurred between 0 and 30 days (30-day readmissions), 31-90
      days (3-month readmissions), and 91-365 days (1-year readmissions). Each
      readmission was then assigned to 1 of the 4 categories based on whether they were
      related to the index procedure and whether they were planned. Univariate tests
      were performed for demographic variables based on their type of readmission, and
      logistic regressions were then performed to identify predictors of each
      unplanned, related readmissions. RESULTS: The overall 30-day readmission rate was
      21.9% (n = 213). The unplanned, related readmission cohort (n = 83) had the
      highest readmission rate of 8.5%. The related, planned readmission rate was 5.9%
      (n = 58), while the unrelated, unplanned readmission rate was 5.6% (n = 55). In
      contrast, the overall 1-year readmission rate was 40.0% (n = 389), with the
      largest category being unplanned, unrelated readmissions at 19.7% (n = 191). The
      unplanned, related readmission rate was 8.7% (n = 85), whereas the planned,
      related readmission rate was 5.7% (n = 55). Compared with other types of
      readmissions, unplanned, related readmissions tended to affect patients who were
      younger, had poor glycemic control, and had higher body mass indexes (BMIs).
      Multivariate predictors of unplanned, related readmissions were poor glycemic
      control at 3 months (odds ratio [OR]: 2.16, P = 0.03), and BMI at 30 days (OR:
      1.06, P = 0.04) and 1 year (OR: 1.05, P = 0.04). CONCLUSIONS: Readmissions have
      varying risk factors depending on their category; targeting glycemic control and
      obesity may reduce unplanned, related readmissions.

PMID- 30218829
TI  - Carotid Artery Entrapment by the Hyoid Bone-A Rare Cause of Recurrent Strokes in
      a Young Patient.
AB  - The search for etiology of stroke in a young patient may present a diagnostic
      challenge. In rare cases, chronic trauma to the carotid artery may be the cause
      of cerebral thromboembolic events. The hyoid bone lies in close proximity to the
      carotid artery bifurcation, and anatomic variants have been implicated in carotid
      compression, stenosis, dissection, and pseudoaneurysm. We report a case of
      recurrent strokes in a 32-year-old woman due to an elongated hyoid bone causing
      thrombus formation in her right internal carotid artery (ICA), resulting in
      recurrent embolic strokes confirmed on diffusion-weighted magnetic resonance
      imaging. Computed tomography angiography of the neck and head demonstrated the
      right hyoid bone was located between the ICA and external carotid artery (ECA),
      just above the carotid bifurcation, with residual nonocclusive thrombus in the
      right ICA. Carotid duplex ultrasonography confirmed that with the neck in neutral
      position, the hyoid was located between the ICA and ECA; however, with neck
      rotation, the hyoid slipped across the ICA and out of the bifurcation. There was
      no evidence of carotid stenosis. After an initial course of anticoagulation and
      antiplatelet therapy, resection of the greater cornu of the hyoid bone with
      release of the right ICA was performed. One year postoperatively, the patient had
      complete return of neurologic function and had no further neurologic events.
      Hyoid bone entrapment of the carotid artery is a rare etiology of thromboembolic
      stroke caused by repetitive local trauma. The diagnosis can be confirmed by
      carotid duplex with provocative maneuvers. Partial hyoid resection is a safe and
      effective treatment to relieve recurrent symptoms. Hyoid bone entrapment may be
      an important and under-recognized cause of stroke in young adults.

PMID- 30218830
TI  - Evidence for Cerebral Embolic Prevention in Transcatheter Aortic Valve
      Implantation (TAVI) and Thoracic Endovascular Aortic Repair (TEVAR).
AB  - PURPOSE: Embolic stroke is a formidable complication of transcatheter aortic
      valve implantation (TAVI) and thoracic endovascular aortic repair (TEVAR).
      Mechanical strategies to reduce the risk of ischemic embolic lesions include
      embolic protection devices (EPD) and carbon dioxide flushing (CDF). This study
      aims to assess the efficacy for EPD and CDF uses in TAVI and TEVAR. METHODS: A
      literature review was performed according to Preferred Reporting Items for
      Systematic reviews and Meta-Analysis (PRISMA). All searches were done via Pubmed,
      OvidSP, Medline, Web of Science Core Collection, and Cochrane Library. Conference
      abstracts and proceedings were included. Those that were out of scope of interest
      and review articles were excluded. RESULTS: 18 studies fulfilled the inclusion
      criteria out of 456 articles searched. Regarding EPD use in TAVI, systematic
      review comparing EPD with no-EPD showed smaller total volume of cerebral lesions,
      and smaller volume per lesion in patients with EPD in all studies. They also
      performed better in post-operative neurocognitive assessments, but could not
      demonstrate clinical prevention of embolic stroke in all studies. While for EPD
      use in TEVAR, capture of embolic debris and absence of early post-operative
      neurocognitive deficit were demonstrated in all cases of 2 prospective pilot
      studies. Concerning CDF in TEVAR, significant reduction in gaseous emboli
      released during stent-graft deployment was shown by 1 in-vitro study. Successful
      CDF application in all patients, with only 1 case of post-operative non-disabling
      stroke, was also demonstrated by 1 cohort study. CONCLUSION: This systematic
      review of medical literature has demonstrated the safety and feasibility of EPD
      use in TAVI. Although improvements in clinical outcomes have yet been
      demonstrated, there was level I evidence showing reduced embolic lesions in
      imaging. EPD and CDF uses in TEVAR were suggested, but evidence remained
      inadequate to support routine clinical use.

PMID- 30218831
TI  - A Rare Case of Tibioperoneal Arterial Trunk Entrapment Caused by a Fibular
      Osteochondroma.
AB  - BACKGROUND: Osteochondromas or exostoses are the most common benign tumors of the
      bones, which appear during the growth period. The involvement of lower
      extremities is common, particularly in metaphyseal structures of the femur and
      humerus and around the knee joint. However, the incidence of the development of
      the tumor at the proximal fibula is rare. The most common signs and symptoms of
      the disease are pain, pulsatile mass, limb swelling, neurologic sequelae, bursa
      formation with subsequent bursitis, and impairment of the developmental growth.
      Vascular complications are rare, yet osteochondromas can cause catastrophic
      arterial complications threatening the life of the patient if they occur and can
      include vessel perforation and thrombosis, arterial thromboembolic events, and
      pseudoaneurysm formation. METHODS: We report a case of a 24-year-old male patient
      presenting with tibioperoneal arterial trunk entrapment caused by a massive
      osteochondroma derived from the proximal fibula. A combined vascular-orthopedic
      approach was initiated with the excision of the tumor, in which the neurovascular
      structures (tibial nerve, popliteal artery and vein, anterior tibial artery, and
      tibioperoneal trunk) were carefully recognized and protected. RESULTS: The
      postoperative course of the patient was uneventful. CONCLUSIONS: High clinical
      suspicion of a vascular complication should be raised by physicians when
      investigating a young patient with a suspected osseous tumor in the popliteal
      fossa and symptomatology of concurrent peripheral arterial disease. Prompt
      surgical management is crucial for the salvage of the affected limb in cases of
      arterial involvement. Furthermore, quick surgical exposure of the mass and
      regular postoperative follow-up check minimizes the risk of irreparable
      impairments and tumor recurrence.

PMID- 30218832
TI  - Endobronchial Forceps-Assisted Removal of Gianturco Z-Stents from the Right
      Atrium.
AB  - Endovascular treatment of malignant intrahepatic inferior vena cava stenosis
      involves venoplasty and stenting. Intravascular migration is a complication
      associated with stents. This technical report describes the retrieval of migrated
      intracardiac Gianturco Z-stents using rigid endobronchial forceps.

PMID- 30218833
TI  - Combined Type III and Type II Endoleaks after Endovascular Aneurysm Repair:
      Presentation of 2 Cases and a Literature Review.
AB  - Although endovascular aneurysm repair is a feasible option for high-risk patients
      resulting in lower perioperative mortality when compared with open repair, the
      need for reintervention and long-term follow-up affects its use. The aim of the
      current report is to present 2 cases of patients with type IIIa endoleak from
      limb disconnection (one patient with double-bilateral endoleak) combined with a
      late type II endoleak and symptomatic sac growth treated in our department. We
      also performed a literature review about type III endoleaks and their treatment
      options.

PMID- 30218834
TI  - Inferior Vena Cava Filter Resulting in Perforation and Massive Retroperitoneal
      Hematoma Presenting as Acute Onset of Lower Extremity Weakness.
AB  - Perforation of inferior vena cava (IVC) filter struts is a common incidental
      finding on postoperative computed tomography (CT) scans that is not associated
      with bleeding or major complications. However, in rare circumstances, it can be
      associated with hemorrhage requiring immediate removal. We present a case of a 62
      year-old man who developed abdominal pain and right lower extremity weakness 2
      weeks after treatment of a pulmonary embolism with IVC filter placement and
      anticoagulation. A CT scan revealed a large right-sided retroperitoneal hematoma
      with active extravasation from the IVC filter struts that had perforated the IVC
      wall. He underwent a hybrid operation with endovascular retrieval of the IVC
      filter and concomitant IVC primary repair combined with evacuation of the
      hematoma, causing nerve compression. Postoperatively, he regained normal sensory
      and motor function. Perforation of IVC filter struts is usually asymptomatic, but
      in rare circumstances, it can cause hemorrhage requiring immediate removal and
      IVC repair. Surgical intervention is indicated in the setting of a large hematoma
      with nerve or vessel compression and may require a combined endovascular and open
      approach.

PMID- 30218835
TI  - Towards biobanking technologies for natural and bioengineered multicellular
      placental constructs.
AB  - Clinical application of a large variety of biomaterials is limited by the
      imperfections in storage technology. Perspective approaches utilizing low
      temperature storage are especially challenging for multicellular structures, such
      as tissues, organs, and bioengineered constructs. Placenta, as a temporary organ,
      is a widely available unique biological material, being among the most promising
      sources of various cells and tissues for clinical and experimental use in
      regenerative medicine and tissue engineering. The aim of this study was to
      analyse the mechanisms of cryoinjuries in different placental tissues and
      bioengineered constructs as well as to support the viability after low
      temperature storage, which would contribute to development of efficient
      biobanking technologies. This study shows that specificity of cryodamage depends
      on the structure of the studied object, intercellular bonds, as well as
      interaction of its components with cryoprotective agents. Remarkably, it was
      possible to efficiently isolate cells after thawing from all of the studied
      tissues. While the outcome was lower in comparison to the native non-frozen
      samples, the phenotype and expression levels of pluripotency genes remained
      unaffected. Further progress in eliminating of recrystallization processes during
      thawing would significantly improve biobanking technologies for multicellular
      constructs and tissues.

PMID- 30218836
TI  - ROS-induced NO generation for gas therapy and sensitizing photodynamic therapy of
      tumor.
AB  - This study reports a tumor-specific ROS-responsive nanoplatform capable of the
      combination of nitric oxide (NO)-based gas therapy and sensitized photodynamic
      therapy (PDT). The nanoplatform is constructed on porous coordination network
      (PCN), which contains NO donor L-Arg and is concurrently coated with cancer cell
      membrane (L-Arg@PCN@Mem). Under near infrared light (NIR) irradiation, L
      Arg@PCN@Mem produces plenty of reactive oxygen species (ROS) directly for PDT
      therapy, while a part of ROS take the role of oxidative to converse L-Arg into NO
      for combined gas therapy. The results indicate that the transformation of ROS to
      NO can enhance PDT efficacy in hypoxic tumors owing to the ability of NO in
      freely diffusing into deep hypoxic tumor site. Moreover, homologous targeting
      function originated from the coating of cancer cells membrane further improves
      the tumor treatment effect owing to the biotargeting toward homologous tumors.
      This L-Arg@PCN@Mem nanoplatform provides a new therapy paradigm of overcoming the
      hypoxia barrier of tumor therapy, and holds great potential for the treatment of
      tumor and NO-related diseases.

PMID- 30218837
TI  - A randomized controlled effectiveness trial of training strategies in cognitive
      processing therapy for posttraumatic stress disorder: Impact on patient outcomes.
AB  - This randomized controlled hybrid implementation/effectiveness trial aimed to
      compare the impact of three different models of training and consultation by
      examining the PTSD treatment outcomes achieved by therapists who were learning a
      front-line recommended psychotherapy for posttraumatic stress disorder (PTSD),
      Cognitive Processing Therapy (CPT; Resick, Monson, & Chard, 2017). Therapists (N
      = 134) were randomized into one of three conditions after attending a standard
      CPT training workshop: No Consultation with delayed feedback on CPT fidelity,
      Standard Consultation involving discussion and conceptualization of cases without
      session audio review, and Consultation Including Audio Review, which included a
      review of segments of audiorecorded CPT sessions. Across all training conditions,
      the patients treated by these therapists (N = 188) evidenced statistically
      significant reductions in PTSD symptoms, (d = -0.95 to -1.78), comorbid symptoms
      and functioning (d = -0.27 to -0.51). However, patients of therapists in the
      Standard Consultation condition (DeltaPTSD = - 19.64, d = -1.78) experienced
      significantly greater improvement than those in the No Consultation condition
      (DeltaPTSD = - 10.54, d = -0.95, DeltaDEV = 6.30, DeltaParms = 2, p = .043). This
      study demonstrates that patients who receive evidence-based psychotherapy for
      PTSD in routine care settings can experience significant symptom improvement. Our
      findings also suggest that to maximize patient benefit, therapist training should
      include consultation, but that audio review of sessions during consultation may
      not be necessary, at least for structured protocols. Implications for
      implementation, including the reduction of burden and cost of post-workshop
      support, are discussed.

PMID- 30218838
TI  - Mapping specific vulnerability of multiple confined and unconfined aquifers by
      using artificial intelligence to learn from multiple DRASTIC frameworks.
AB  - An investigation is presented to improve on the performances of the Basic DRASTIC
      Framework (BDF) and its variation by the Fuzzy-Catastrophe Framework (FCF), both
      of which provide an estimate of intrinsic aquifer vulnerabilities to
      anthropogenic contamination. BDF prescribes rates and weights for 7 data layers
      but FCF is an unsupervised learning framework based on a multicriteria decision
      theory by integrating fuzzy membership function and catastrophe theory. The
      challenges in the paper include: (i) the study area comprises confined and
      unconfined aquifers and (ii) Artificial Intelligence (AI) is used to run Multiple
      Framework (AIMF) in order to map specific vulnerability due to a specific
      contaminant. Predicted results by AIMF are referred to as Specific Vulnerability
      Indices, as the learned VIs are referenced to site-specific nitrate-N. The
      results show that correlation coefficient between BDF or FCF with nitrate-N is
      lower than 0.7 but the AIMF strategy improves it to greater than 0.95. The
      results are evidence for the proof-of-concept for transforming frameworks to
      models capable of further learning.

PMID- 30218839
TI  - Combined three-dimensional gait and plantar pressure analyses detecting
      significant functional deficits in children with juvenile idiopathic arthritis.
AB  - BACKGROUND: Children suffering from juvenile idiopathic arthritis (JIA), a
      heterogeneous group of chronic inflammatory joint diseases, adapt to individual
      gait patterns to avoid loading of inflamed, swollen and painful joints. As the
      interpretability of previous studies is limited, this study aims to assess the
      functional capacity, loads and plantar pressure distribution in the gait of a
      homogeneous JIA group. RESEARCH QUESTION: Does a symmetrical lower limb joint
      involvement influence the gait dynamics in JIA patients, and how are the results
      of three-dimensional gait analysis (3DGA) and pedobarography related? METHODS:
      Fifty JIA patients with symmetrical hip, knee and ankle joint arthritis and 27
      healthy controls performed 3DGA and pedobarography at self-selected walking
      speeds. Kinematics and kinetics of lower limb joints were retrospectively
      compared in range of motion and in time-normalized waveforms. Plantar load was
      evaluated by measuring peak pressure, pressure-time integral and maximum force of
      the whole foot and ten selected foot regions. 1D-SPM analysis, parametric and non
      parametric statistical significance tests and correlation coefficients were used
      for statistical analysis. RESULTS: JIA patients had a significantly slower
      walking speed with an anteriorly tilted pelvis and a reduced extension motion of
      all joints of the lower limb. The horizontal ground reaction forces and generated
      hip and ankle power during propulsion phase were small. Patients experienced
      reduced loading at toe regions, which correlated with limited ankle
      plantarflexion motion in the push-off phase. The total peak pressure was
      significantly increased and loads at lateral midfoot and metatarsal regions were
      higher in patients. SIGNIFICANCE: Symmetrical lower limb arthritis is linked to
      crouch-like gait and restricted gait dynamics with increased total peak pressure.
      The results confirm earlier results of 3DGA and provide new insights regarding
      waveform analysis and plantar loading in JIA patients. The used methods help to
      design individualized functional treatment of JIA patients.

PMID- 30218840
TI  - Disparities in Pediatric Provider Availability by Insurance Type After the ACA in
      California.
AB  - OBJECTIVE: To examine insurance-based disparities in provider-related barriers to
      care among children in California in the wake of changes to the insurance market
      resulting from the Affordable Care Act. METHODS: Our sample included 6514
      children (ages 0 to 11 years) from the 2014-2016 California Health Interview
      Survey. We examined parent reports in the past year of 1) having trouble finding
      a general provider for the child, 2) the child not being accepted by a provider
      as a new patient, 3) the child's health insurance not being accepted by a
      provider, or 4) any of the above. Multivariable models estimated the associations
      of insurance type-Medi-Cal (Medicaid), employer-sponsored insurance, or privately
      purchased coverage-and parent reports of these problems. RESULTS: Approximately
      8% of parents had encountered at least one of these problems. Compared with
      parents of children with employer-sponsored insurance, parents of children with
      Medi-Cal or privately purchased coverage had over twice the odds of experiencing
      at least one of the barriers. Parents of children with Medi-Cal had over twice
      the odds of being told a provider would not accept their children's coverage or
      having trouble finding a general provider and 3 times the odds of being told a
      provider would not accept their children as new patients. Parents of children
      with privately purchased coverage had over 3 times the odds of being told a
      provider would not accept their children's coverage. CONCLUSIONS: Our study found
      significant disparities in provider-related barriers by insurance type among
      children in California.

PMID- 30218842
TI  - The effect of being left home alone at age 3 years on schizotypy and antisocial
      behavior at ages 17 and 23 years.
AB  - OBJECTIVE: Negative home environments are associated with both schizophrenia
      spectrum disorders and crime, but whether this is due to the social or cognitive
      sequelae of such environments is unclear. This study investigates the effect of
      early home environments on adult mental health. METHOD: Using data from the
      Mauritius Child Health Project, a multiple time-point prospective study where all
      children born in 1969 in two towns (Quatre Bornes and Vacaos) were recruited at
      age 3 years (N = 1794), a group of children left home alone at age 3 (n = 34)
      were compared to children cared for by siblings/relatives (n = 222), or by
      mothers (n = 1498) on antisocial behavior and schizotypal personality at ages 11,
      17, and 23 years. RESULTS: Home alone children showed higher scores on psychotic
      behavior and conduct disorder at age 17, and also schizotypal personality and
      crime at 23 years compared to the other groups. No negative behavioral or
      cognitive effects were observed at age 11. Findings were not accounted for by
      social adversity or ethnicity and appear to be 'sleeper effects' in that they do
      not emerge until later adolescence and into adulthood. CONCLUSIONS: Findings
      appear to be the first to show the negative effects of dual-parental daytime
      absence on adult schizotypy and crime, a finding that cannot be accounted for by
      verbal and spatial cognitive impairments. Results suggest an early common
      psychosocial denominator to the two comorbid conditions of antisocial behavior
      and schizotypy.

PMID- 30218841
TI  - Functional reorganisation and recovery following cortical lesions: A preliminary
      study in macaque monkeys.
AB  - Damage following traumatic brain injury or stroke can often extend beyond the
      boundaries of the initial insult and can lead to maladaptive cortical
      reorganisation. On the other hand, beneficial cortical reorganisation leading to
      recovery of function can also occur. We used resting state FMRI to investigate
      how cortical networks in the macaque brain change across time in response to
      lesions to the prefrontal cortex, and how this reorganisation correlated with
      changes in behavioural performance in cognitive tasks. After prelesion testing
      and scanning, two monkeys received a lesion to regions surrounding the left
      principal sulcus followed by periodic testing and scanning. Later, the animals
      received another lesion to the opposite hemisphere and additional testing and
      scanning. Following the first lesion, we observed both a behavioural impairment
      and decrease in functional connectivity, predominantly in frontal-frontal
      networks. Approximately 8 weeks later, performance and connectivity patterns both
      improved. Following the second lesion, we observed a further behavioural deficit
      and decrease in connectivity that showed little recovery. We discuss how
      different mechanisms including alternate behavioural strategies and
      reorganisation of specific prefrontal networks may have led to improvements in
      behaviour. Further work will be needed to confirm these mechanisms.

PMID- 30218843
TI  - Evidence for distinct steps in response preparation from a delayed response
      paradigm.
AB  - Task parameters still affect reaction times even when all necessary information
      for executing an action is presented prior to a Go signal to execute the action.
      Hypotheses in terms of short-term memory capacity, residual activation, and a
      separate motor-programming stage have been suggested to explain what can and
      cannot be prepared prior to a delayed Go signal. To test these hypotheses, we
      used a delayed response task, in which participants were to initiate a movement
      at onset of an imperative Go signal following the target stimulus. Across
      Experiments 1-3 we varied task properties including stimulus type, information
      uncertainty and response complexity, respectively, while controlling other
      factors. We also varied the time available to process the response by randomly
      varying the interval between onset of the target and the Go signal (i.e., the
      stimulus onset asynchrony, or SOA). If the preparation process is completed
      before initiation, the examined factor should display a strong interaction with
      SOA, with its effect disappearing at long SOAs. Our results showed strong,
      weaker, and no interaction patterns for the three factors, respectively, favoring
      the separate stage hypothesis, according to which response preparation is
      separated into steps to arrange kinematic specifications into muscle-controllable
      terms.

PMID- 30218845
TI  - Still life? Children's understanding of the reality status of museum taxidermy.
AB  - Taxidermied animals provide an important source of information about the natural
      world, but failure to understand their reality status may result in missed
      learning opportunities for museum visitors. This study explored 4-10-year-old
      children's and adults' (N = 207) reality status judgments and biological and
      authenticity property attributions for a taxidermied rabbit during a museum
      visit. The aim was to examine their understanding of its former status as a
      living animal and its current status as an authentic piece of natural history,
      under different presentation conditions: (a) as a touchable exhibit; (b) inside
      an exhibition case-untouchable; and (c) in an experimental context paired with a
      toy rabbit-both touchable. Analysis revealed that there was an increase with age
      both in judgments that taxidermy was real and authentic and in accuracy of
      biological property attributions. The toy condition resulted in more accurate
      reality judgments, whereas the touchable condition resulted in more accurate
      biological property attributions. There was no effect of age or condition on
      authenticity property attributions. Accuracy of biological property attributions
      was also associated with reality status judgments, whereby understanding the real
      and authentic nature of taxidermy was associated with understanding its
      biological status. Implications for the development of biological cognition and
      museum learning are discussed.

PMID- 30218844
TI  - Rationale and design of the EVOLVE Short DAPT Study to assess 3-month dual
      antiplatelet therapy in subjects at high risk for bleeding undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: While extended dual antiplatelet therapy (DAPT) with aspirin and a
      platelet (P2Y12) inhibitor after percutaneous coronary intervention (PCI) reduces
      the risk of stent thrombosis (ST) and myocardial infarction (MI), it also
      increases bleeding. Newer generation drug-eluting stents with bioabsorbable
      polymer coatings may reduce thrombotic events and allow abbreviated DAPT in
      selected patients. The EVOLVE Short DAPT study is designed to evaluate the safety
      of 3-month DAPT in high bleeding risk subjects treated with the SYNERGY
      bioabsorbable polymer everolimus-eluting stent. TRIAL DESIGN: EVOLVE Short DAPT
      is a prospective, single-arm, international study that enrolled 2009 high risk
      bleeding subjects (defined as age >=75 years, chronic anticoagulation, major
      bleeding within 12 months, history of stroke, renal insufficiency/failure, or
      thrombocytopenia) who underwent PCI with the SYNERGY stent. Subjects presenting
      with acute MI or complex lesions were excluded. After 3 months treatment with
      DAPT (except those on anticoagulant in whom aspirin is optional), subjects free
      from stroke, MI, revascularization or ST will be eligible to discontinue P2Y12
      inhibitor, but continue aspirin. Co-primary endpoints assessed between 3-15
      months are: i) death/MI compared for non-inferiority with propensity-adjusted
      historical group receiving 12-month DAPT, and ii) definite/probable ST compared
      to a performance goal. The secondary endpoint is the rate of bleeding in subjects
      not receiving chronic anticoagulation compared for superiority against a
      propensity-adjusted historical control. CONCLUSION: The EVOLVE Short DAPT study
      will prospectively define the safety of DAPT discontinuation at 3 months in high
      bleeding risk patients treated with the SYNERGY stent.

PMID- 30218846
TI  - Changing one's focus of attention alters the structure of movement variability.
AB  - : Substantial evidence supports the beneficial effect of an external (vs.
      internal) focus of attention on task performance during goal-directed movements.
      Counter-intuitively, an external focus has also been shown to increase joint
      level movement variability. OBJECTIVE: To determine whether shifting attentional
      focus can alter the structure of movement variability, thereby offering a
      probable mechanistic explanation for how adopting an external focus of attention
      might confer its benefits. METHODS: Thirty-five healthy adults (age 23-55)
      performed unipedal hopping under three different attentional foci: natural (no
      directed focus), internal focus, and external focus. Uncontrolled manifold
      analysis was used to examine the structure of movement variability with respect
      to stabilization of leg orientation and vertical leg length during hopping.
      Takeoff/landing event bin and stance phase integrals of performance-irrelevant
      and performance-destabilizing variability were compared across focus conditions.
      RESULTS: Accuracy of hopping in place improved with both external and internal
      foci compared to the natural condition (.004 <= p <= .035). External focus, to a
      greater degree than internal focus, destabilized leg orientation at takeoff and
      landing compared to the natural condition (.001 <= p <= .038). External focus
      increased - but internal focus decreased - leg length stabilization throughout
      stance compared to the natural condition (p < .001). CONCLUSION: External focus
      was superior to internal and natural focus conditions in terms of increasing
      flexibility within the system to orient the leg differently at takeoff and
      landing to compensate for unintentional drift during hopping. An external focus
      increased leg length stabilization in stance by preferentially increasing the
      subset of variability that explores multiple successful performance options.
      These results provide an understanding of the mechanism underlying external focus
      benefits - improving movement variability/coordination.

PMID- 30218847
TI  - Lower extremity joint stiffness during walking distinguishes children with and
      without autism.
AB  - How children with Autism Spectrum Disorder (ASD) and peers with typical
      development (TD) modulate lower extremity stiffness during walking could identify
      a mechanism for gait differences between groups. We quantified differences in
      lower extremity joint stiffness and linear impulses, along the vertical and
      anterior/posterior axes during over-ground walking in children with ASD compared
      to age- and gender-matched children with TD. Nine age- and gender-matched pairs
      of children, aged 5-12 years, completed the current study. Joint stiffness and
      linear impulses were computed in four sub-phases of stance: loading response, mid
      stance, terminal stance, and pre-swing. The Model Statistic technique (alpha =
      0.05) was used to test for statistical significance between the matched-pairs for
      each variable and sub-phase. Furthermore, dependent t-tests (alpha = 0.05) were
      utilized, at the group level, to determine whether significant differences
      existed between sub-phases. Results indicate that children with ASD may exhibit
      greater stiffness in pre-swing, and thus, produce inefficient propulsive forces
      during walking. We attribute these differences to sensory processing dysfunction
      previously observed in children with ASD.

PMID- 30218848
TI  - Whole body vibration of different frequencies inhibits H-reflex but does not
      affect voluntary activation.
AB  - This study aimed to investigate the effects of whole-body vibration (WBV) at a
      frequency spectrum from 20 to 50 Hz on the Hoffmann (H) reflex and the voluntary
      motor output of ankle plantar-flexor muscles. A single-group (n: 8), repeated
      measures design was adopted with four conditions: standing (no vibration), 20, 35
      and 50 Hz, each lasting one minute. H-reflex of the soleus muscle, maximal
      voluntary contraction (MVC) and central activation ratio (CAR) of the plantar
      flexors were evaluated before, 1 and 5 min after each frequency condition. H
      reflex decreased by 36.7% at 20 Hz, by 28% at 35 Hz, and by 34.8% at 50 Hz after
      one minute from WBV compared to baseline. Neither MVC nor CAR changed after WBV
      at all frequency conditions. The short-term, acute inhibition of the H-reflex
      after WBV at 20, 35 and 50 Hz suggested that decreased excitability of spinal
      motoneurons is not frequency dependent. On the other hand, the lack of vibration
      induced effects on MVC and CAR indicated that a 1-min WBV stimulus is not
      sufficient to affect the voluntary motor output.

PMID- 30218850
TI  - Instructor-led vs. peer-led debriefing in preoperative care simulation using
      standardized patients.
AB  - BACKGROUND: Debriefing involves the active participation of learners to identify
      and close gaps in knowledge and skills. Varied debriefing methods are used in
      simulation, but no empirical studies have examined the effectiveness of peer-led
      debriefing in simulation using standardized patients. The purpose of this study
      was to compare the effects of two debriefing methods (instructor-led vs. peer
      led) on nursing skills, knowledge, self-confidence, and quality of debriefing
      among undergraduate nursing students in South Korea. METHOD: A nonequivalent
      control group pretest-posttest design was used. Fifty-seven third-year nursing
      students were randomly assigned to instructor-led (n = 26) or peer-led (n = 31)
      debriefing groups after a simulation of preoperative care. Structured questions
      and areas for discussion guided debriefing in both groups. Self-administered
      questionnaires were used to collect data on students' knowledge and self
      confidence in providing preoperative care. Faculty evaluated students' nursing
      skills during pre- and post-simulation practice. Students evaluated the quality
      of the debriefings. RESULTS: Nursing skills for preoperative care (p < .001) and
      the quality of debriefing (p < .001) were statistically higher in the instructor
      led group compared to the peer-led group. There were no statistically significant
      differences in knowledge (p = .445) and self-confidence (p = .686). Knowledge and
      self-confidence from pre-test to posttest were improved in both groups.
      CONCLUSION: The instructor-led debriefing showed improved nursing skills and
      higher quality debriefing. However, peer-led debriefing led by a non-trained peer
      also rendered positive results. Thus, peer-led debriefing may be considered a
      useful strategy for improving nursing students' self-confidence.

PMID- 30218849
TI  - A new approach to multi-professional end of life care training using a sequential
      simulation (SqS SimulationTM) design: A mixed methods study.
AB  - BACKGROUND: A need for improved education and training for hospital staff caring
      for patients in the last year of life was identified at an urban UK hospital.
      Sequential Simulation (SqS SimulationTM) is a type of simulation that recreates a
      patient's journey, considering the longitudinal element of care and how this
      might impact on the patient's experiences, wishes and needs. OBJECTIVES: The aim
      of this study was to investigate a new end of life care training intervention for
      multi-professional hospital staff, and its effect on their confidence in managing
      patients at the end of their life. SETTING/PARTICIPANTS: Based on the results of
      a formal Training Needs Analysis, four SqS SimulationTM specialty-based courses
      were designed for general medical and surgical multidisciplinary teams in an
      acute UK hospital. METHODS: Over three months, seven SqS SimulationTM sessions
      were attended by fifty-seven multidisciplinary healthcare professionals. A quasi
      experimental mixed-methods study was conducted using open and closed-ended
      questionnaires, pre and post-intervention. Changes in course attendees'
      confidence levels were analysed and qualitative data from free-text answers
      informed potential reasons for any differences identified. RESULTS: Confidence
      improved for all professional cohorts (p < 0.001). The differences were found to
      be highly significant for 'doctors' (p < 0.001), significant for 'therapists' (p
      = 0.02) and not significant for the 'nurses' cohort (p = 0.238). This was
      explored further using a qualitative explanatory framework. Categories included:
      Communicating with Families; Teamwork; Goal Planning; Do Not Attempt
      Cardiopulmonary Resuscitation; Course Usefulness; Prior Training; and Clinical
      Experience. CONCLUSION: This study has shown an overall improvement in confidence
      across disciplines after attending a SqS SimulationTM course. The differences in
      quantitative results between disciplines were explored through the qualitative
      data and revealed a difference in what the professionals gained from it. Further
      studies are required to assess its effectiveness in maintaining confidence of end
      of life care in practice, as well as its benefit to patient outcomes.

PMID- 30218851
TI  - Detection of bovine herpesvirus 1 in cumulus-oocyte complexes of cows.
AB  - Bovine herpesvirus 1 (BoHV-1) is the causative agent of infectious bovine
      rhinotracheitis (IBR) and is also associated with reproductive failure. This
      study investigated the presence of BoHV-1 in cumulus-oocyte complexes (COCs) of
      naturally-infected cows without clinical signs of IBR. The presence of BoHV-1 in
      COCs was evaluated by immunofluorescence using confocal laser scanning
      microscopy. Blood samples and ovaries from 82 cows that had not been vaccinated
      against BoHV-1 were collected for serological analysis. COCs were divided into
      two pools: COCs derivate from seropositive cows and from seronegative cows. Then,
      the samples were processed for confocal microscopy analysis. The results
      indicated that 61% (50/82) of cows were seropositive for BoHV-1. A total of 719
      COCs were obtained from the cows and processed. None of 276 COCs from the 32
      seronegative cows presented BoHV-1. However, BoHV-1 was present in the cytoplasm
      of cumulus cells from 158 out of 443 COCs aspirated from the seropositive cows.
      The detection of BoHV-1 in the COCs of seropositive cows suggests that the COCs
      of naturally-infected, asymptomatic cows may be infected with BoHV-1.

PMID- 30218852
TI  - The gender discrepancy in high-risk behaviour outcomes in adolescents who have
      experienced cyberbullying in Indonesia.
AB  - OBJECTIVE: Adolescent cyberbullying and high-risk behaviour outcomes has been a
      major concern in the last few years. Gender discrepancy is an important component
      that predicts the outcomes. This study aimed to elaborate and identify the
      association between cyberbullying experience and high-risk behaviour outcomes
      based on gender differences among adolescents in Indonesia. METHOD: A cross
      sectional study that involved junior and senior high schools in Jakarta. There
      were 2917 adolescents who took part in this study. The cyberbullying
      questionnaire was used to identify the cyberbullying experienced. High-risk
      behaviour included in this study was tobacco smoking, alcohol consumption, and
      self-harm behaviour. Chi-Square test and odds ratio analysis were applied through
      SPSS for Mac. RESULTS: The highest proportion in this study was composed of
      adolescents of both genders who acted as victim/perpetrator (52.25%). Adolescent
      males who indulged in cyberbullying showed an increased risk for cigarette
      smoking (OR = 2.97); male adolescents who were victims and victim/perpetrator of
      cyberbullying had a higher risk to consume alcohol (OR = 2.96 & OR = 6.93).
      Meanwhile, the risk of self-hurting behaviour increased for both female and male
      with cyberbullying victimization (OR = 3.68 & OR = 2.97). Female adolescents who
      acted as victim/perpetrator had a higher risk of suicidal thoughts and attempting
      suicide (OR = 1.90 & OR = 2.11); and they were also at risk of consuming alcohol
      (OR = 2.84). CONCLUSION: Cyberbullying returned negative impacts on both genders
      of adolescents. Boys showed a greater tendency to externalize while girls showed
      a greater tendency to internalize. Mental health promotion that is designed
      specifically for both genders might address the adolescents' needs.

PMID- 30218853
TI  - Validation of the Bangla version of the Dimensional Obsessive-Compulsive Scale.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a common and severe
      psychiatric illness which affects about 1-3% of the population across the globe.
      The Dimensional Obsessive-Compulsive Scale (DOCS) is a 20-item self-report
      instrument that assesses the severity of OCD in four dimensions. OBJECTIVES: We
      aimed to adapt and validate the DOCS in Bangla. METHODS: This validation study
      was conducted from January 2016 to July 2017 using purposive sampling technique.
      A total of 100 OCD patients were recruited from OCD clinic of Bangabandhu Sheikh
      Mujib Medical University after considering the inclusion and exclusion criteria.
      We applied Bangla version of DOCS to collect data and assessed different forms of
      validity and reliability. RESULTS: Cronbach's alpha of DOCS Bangla was 0.93 which
      signifies a good internal consistency. Cronbach's alpha of contamination domain
      was 0.92; responsibility domain 0.94, thought domain 0.91 and symmetry domain was
      found 0.93. Four factors were extracted from exploratory factor analysis with
      varimax rotation. Pearson correlation was 0.73 between the DOCS Bangla total
      global score and the Y-BOCS total score which signifies good criterion validity.
      CONCLUSION: DOCS Bangla is a psychometrically reliable and valid tool for use in
      clinical settings, research and primary care setting to diagnose and manage OCD
      for Bangla speaking population.

PMID- 30218854
TI  - Protective effect of enzymatic hydrolysates from seahorse (Hippocampus
      abdominalis) against H2O2-mediated human umbilical vein endothelial cell injury.
AB  - Oxidative stress-mediated endothelial dysfunction and LDL oxidation have been
      implicated in the pathogenesis of atherosclerosis. Thus, the protection of the
      endothelial cells against oxidative stress-mediated injury and the inhibition of
      LDL oxidation by the use of antioxidants are a good strategy against
      atherosclerosis development. Here, we investigated the protective effect and the
      inhibition of LDL oxidation of seahorse H. abdominalia hydrolysates by Alcalase
      (SHAH). SHAH showed higher antioxidant activities by measuring DPPH, ABTS+, and
      ORAC assays than the other hydrolysates. SHAH reduced the formation of
      thiobarbituric acid reactive substance in Cu2+-induced LDL oxidation. In human
      umbilical vein endothelial cell (HUVEC), SHAH ameliorated H2O2-mediated HUVEC
      injury through the restoration of antioxidant enzyme activities and glutathione.
      In addition, SHAH inhibited HUVEC apoptosis through the down-regulation of
      caspase-3 and p53 and the increase bcl-2/bax ratio. These results suggested that
      seahorse H. abdominalia could be developed as potential agents for
      atherosclerosis.

PMID- 30218855
TI  - Uptake-release by MSCs of a cationic platinum(II) complex active in vitro on
      human malignant cancer cell lines.
AB  - In this study, the in vitro stability of cisplatin (CisPt) and cationic
      platinum(II)-complex (caPt(II)-complex) and their in vitro activity
      (antiproliferative and anti-angiogenic properties) were investigated against
      three aggressive human tumor cell lines. caPt(II)-complex shown a high stability
      until 9 days of treatment and displayed a significant and higher activity than
      CisPt against both NCI-H28 mesothelioma (19.37 +/- 9.57 MUM versus 34.66 +/- 7.65
      MUM for CisPt) and U87 MG glioblastoma (19.85 +/- 0.97 MUM versus 54.14 +/- 3.19
      for CisPt). Mesenchymal Stromal Cells (AT-MSCs) showed a significant different
      sensitivity (IC50 = 71.9 +/- 15.1 MUM for caPt(II)-complex and 8.7 +/- 4.5 MUM
      for CisPt) to the antiproliferative activity of caPt(II)-complex and CisPt. The
      ability of MSCs to uptake both the drugs in a similar amount of 2.49 pM /cell,
      suggested a possible development of new therapies based on cell mediated drug
      delivery.

PMID- 30218856
TI  - FABP7 promotes cell proliferation and survival in colon cancer through MEK/ERK
      signaling pathway.
AB  - Colon cancer (CC), one of the most frequently diagnosed malignancies deriving
      from the digestive system, has greatly threatened human health and life. Fatty
      acid binding protein 7 (FABP7), an intracellular protein with the tissue-specific
      expression pattern, has been reported to be implicated in diverse types of human
      tumors. However, the biological role of FABP7 in CC is still poorly understood.
      The current study aimed to investigate the role of FABP7 in CC and illuminate the
      potential molecular mechanisms. In this present study, we found that FABP7 was
      highly expressed in CC tissues and cell lines, suggesting the possible
      involvement of FABP7 in CC tumorigenesis. Moreover, functional investigations
      showed that FABP7-overexpression promoted CC cell proliferation, colony
      formation, cell cycle progression and inhibited cell apoptosis; on the contrary,
      FABP7 knockdown produced an inhibitory effects on CC cell proliferation and
      survival. Notably, FABP7 knockdown inhibited colon tumor growth in vivo. In
      addition, mechanistic investigations demonstrated that FABP7 exerted its
      promoting effects on CC cell proliferation and survival through activation of the
      MEK/ERK signaling pathway. Collectively, our data indicate that FABP7 may be used
      as a novel diagnostic bio-marker and a potential therapeutic target for CC.

PMID- 30218857
TI  - Polydatin suppresses proliferation and metastasis of non-small cell lung cancer
      cells by inhibiting NLRP3 inflammasome activation via NF-kappaB pathway.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer death.
      Particularly, inflammation is crucial for the progression of NSCLC. In the past
      few decades, the anti-tumor effects of some traditional Chinese medicinal herbs
      have caused much attention. This study was designed to investigate the effects of
      polydatin in the progression of NSCLC. CCK-8 assay, wound healing assay and
      western blot assay were used to assess the anti-cancer property. Consequently, we
      showed that polydatin inhibited proliferation and migration of NSCLC cells (A549
      and H1299 cells) in a dose-dependent manner. In addition, polydatin suppressed
      the expression of NLRP3, ASC and pro-caspase-1in NSCLC cells. Activation of NLRP3
      inflammasome counteracted the inhibitory effect of polydatin on proliferation and
      migration of NSCLC cells, suggesting that polydatin suppressed progression of
      NSCLC through inhibiting NLRP3 inflammasome activation. Furthermore, polydatin
      was found to down-regulate relative expression of phosphor-NF-kappaB p65 and
      activation of NF-kappaB pathway by TNF-alpha also abolished the inhibitory effect
      of polydatin on proliferation and migration of NSCLC cells. In conclusion, our
      data showed that polydatin acted as an anti-tumor agent to suppress proliferation
      and metastasis of NSCLC cells. The anti-tumor effect of polydatin was possibly
      related to the inhibition of NLRP3 inflammation via the NF-kappaB pathway. Our
      finding suggested that polydatin might be a potential therapeutic candidate in
      the treatment of NSCLC.

PMID- 30218858
TI  - Neuro-protective effects of aloperine in an Alzheimer's disease cellular model.
AB  - Excessive production of amyloid beta (Abeta) induced by familial mutations in
      amyloid precursor protein (APP) and presenilin 1 (PS1) results in neuronal
      oxidative insults, mitochondrial dysfunction, and apoptosis, which play an
      essential role in the pathological development of Alzheimer's disease (AD).
      Aloperine, a quinolizidine alkaloid derived from the leaves of the Sophora plant,
      has displayed multiple pharmacological functions in several chronic diseases. In
      the current study, we investigated the neuro-protective effects of aloperine
      against cytotoxicity in mouse Neuro2a (N2a) cells transfected with Swedish
      amyloid precursor protein (Swe-APP) mutant and presenilin 1 exon 9 deletion
      mutant (N2a/Swe.D9). We found that aloperine ameliorated oxidative stress
      patterns in N2a/Swe.D9 cells by reducing the production of reactive oxygen
      species (ROS) and 4-hydroxy-2-nonenal (4-HNE). Additionally, aloperine treatment
      led to elevated generation of ATP and increased mitochondrial membrane potential
      (MMP) in N2a/Swe.D9 cells. Importantly, we found that aloperine treatment reduced
      the vulnerability of N2a/Swe.D9 cells to H2O2. Aloperine also inhibited apoptosis
      of N2a/Swe.D9 cells via a mitochondria-dependent pathway. These findings suggest
      that aloperine may have pharmacological potential for the treatment of AD.

PMID- 30218859
TI  - Effect of Hypericum humifusum aqueous and methanolic leaf extracts on biochemical
      and histological parameters in adult rats.
AB  - Hypericum genus is traditionally known for its medicinal use and its therapeutic
      and antioxidant effects. However, the toxic effect of this plant has not been
      much explored. Our study aimed at investigating the effect of Hypericum humifusum
      (Hh) leaf extracts on oxidative stress parameters in male rats. For it, we first
      focused on the phytochemical analysis of the aqueous and methanolic extracts of
      Hh leaves. Hence, Wistar rats were treated per gavage for 30 days and divided
      into Control (1 mL/rat, distilled water), A200 group (200 mg/kg body weight (bw)
      aqueous extract), A400 group (400 mg/kg bw aqueous extract), M10 group (10 mg/kg
      bw methanolic extract), M20 group (20 mg/kg bw methanolic extract). The
      phytochemical analysis revealed the presence of tannins, flavonoids, steroids,
      carbohydrates, and phenolic compounds. Biochemical and histological
      investigations were performed in plasma and liver tissue. Liver tissue
      homogenates were used for the measurement of malondialdehyde (MDA), catalase
      (CAT) and superoxide dismutase (SOD) levels. At the same time, alanine
      transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH)
      were assayed in plasma samples. Histological study was also conducted in liver.
      We showed that Hh extracts reduced relative liver weight and increased ALT, AST,
      LDH activities in treated groups compared to control group. These results were
      associated with an increase of MDA levels and a decrease of antioxidant enzyme
      activities (CAT and SOD) in liver tissues of treated rats. Histology of liver
      demonstrated several alterations showing necrosis, altered hepatocytes and
      lymphocyte migration mainly in A200 group and dilated sinusoids, foamy appearance
      of hepatocytes and lymphocyte accumulation in the other treated groups. This
      original work indicated that chronic consumption of Hh leaf extracts has no
      antioxidant effect but instead it induces oxidative stress and enhances markers
      of cell damage which was confirmed by histological study of liver rats.

PMID- 30218860
TI  - Cardioprotective and anti-inflammatory effects of G-protein coupled receptor 30
      (GPR30) on postmenopausal type 2 diabetic rats.
AB  - Diabetic cardiomyopathy is the most common chronic disease in postmenopausal
      women, but the mechanism(s) is unclear. G-protein coupled receptor 30 (GPR30) is
      one of the receptors that binds to 17-beta Estradiol (E2). To date, there is
      little information on GPR30 and its expression in postmenopausal type 2 diabetes
      (T2D) in the heart. The current study hypothesized that GPR30 mediated
      cardioprotective effects of E2 in ovariectomized diabetic rats. Female
      ovariectomized diabetic rats were divided in nine groups: Control, Vehicle,
      Diabetes, Proestrous, Non-proestrous, E2, E2+Vehicle, E2+G15, and G1. G15 is a
      GPR30 antagonist, while G1 is an agonist of GPR30. T2D was induced by high fat
      diet and streptozotocin. E2, G1 and G15 were administrated for four weeks after
      establishment of T2D. Results showed that mean arterial pressure, fasting blood
      glucose and HOMA-IR in diabetic and vehicle groups were alleviated by E2 and G1,
      while salutary effects of E2 were inhibited by G15. Furthermore, E2 and G1
      improved cardiac weight, atherogenic and cardiovascular risk indices; meanwhile
      G15 exacerbated cardiac weight and atherogenic indices. Also, diabetes increased
      cardiac levels of tumor necrosis factor-alpha and interleukin 6 and E2 only
      decreased interleukin 6. Significant decrement in the level of interleukin 10,
      and GPR30 protein were observed in diabetic group, whereas E2 and G1 increased
      the cardiac levels of interleukin 10, and GPR30 protein. Our study suggested that
      beneficial and anti-inflammatory effects of E2 on diabetic cardiomyopathy are
      probably mediated via non-genomic E2 pathways.

PMID- 30218861
TI  - Cinobufacini protects against paclitaxel-induced peripheral neuropathic pain and
      suppresses TRPV1 up-regulation and spinal astrocyte activation in rats.
AB  - Chemotherapy-induced peripheral neuropathic pain is a major limiting factor
      affecting cancer patients. No effective treatment is currently available.
      Cinobufacini, an aqueous extract from toad skin, is a widely used anti-cancer
      drug in China. Clinical evidence has demonstrated the safety and effectiveness of
      cinobufacini in combination with chemotherapy to promote the therapeutic efficacy
      while alleviating side effects, especially cancer-related pain symptoms. In this
      study, the effects of cinobufacini were investigated in a rat model of paclitaxel
      induced peripheral neuropathic pain (PIPNP) to better understand and expand its
      clinical application. A single injection of cinobufacini (2.5 g/kg, i.p.)
      alleviated pre-established PIPNP, as indicated by decreased mechanical and
      thermal hypersensitivity compared with paclitaxel-treated rats. Repeated
      cinobufacini (1.25 and 2.5 g/kg, i.p.), given during the induction of PIPNP,
      prevented the establishment of paclitaxel-induced mechanical and thermal
      hypersensitivity. This preventative effect was associated with suppressed
      paclitaxel-induced TRPV1 up-regulation and spinal astrocyte activation, as well
      as decreased production of spinal TNF-alpha and IL-1beta. These findings reveal
      cinobufacini as a therapeutic potential to treat and prevent paclitaxel-induced
      peripheral neuropathic pain.

PMID- 30218862
TI  - Sedative-hypnotic like effect of 5-methoxyflavone in mice and investigation on
      possible mechanisms by in vivo and in silico methods.
AB  - Flavonoids have been shown to possess central nervous system (CNS) depressant
      effect mediated through the ionotropic GABAA receptors. In the present study, 5
      methoxyflavone was evaluated for sedative-hypnotic like activity in mice and the
      mechanisms involved by employing a battery of tests including molecular docking
      studies. In the open field test, 5-methoxyflavone in various doses (50, 100 and
      150 mg/kg, i.p) exhibited a significant and dose-dependent reduction in the
      spontaneous locomotor activity (F (530) = 87.17 P < 0.001). Pretreatment with 5
      methoxyflavone decreased the latency to sleep induction after pentobarbitone or
      ether administration and also significantly increased the duration of sleep (p <
      0.001). A significant and dose-dependent myorelaxant effect was observed with 5
      methoxyflavone in the inclined plane, horizontal wire test and rota rod test.
      Pretreatment with picrotoxin, bicuculline, glycine, caffeine or NMDA either
      decreased or completely abolished the hypnotic effect of 5-methoxyflavone in
      mice. The above results revealed the involvement of GABAA, adenosine, glycine and
      NMDA receptors in the hypnotic effect of 5-methoxyflavone. The results of in
      silico studies indicated that, 5-methoxyflavone exhibits good binding affinity
      towards these receptors by H-bond interactions. In conclusion, the present study
      identified a novel and potential sedative-hypnotic like effect of 5
      methoxyflavone involving multiple mechanisms.

PMID- 30218863
TI  - Xiao Tan He Wei Decoction reverses MNNG-induced precancerous lesions of gastric
      carcinoma in vivo and vitro: Regulation of apoptosis through NF-kappaB pathway.
AB  - In recent years, Chinese medicine has played an important role in the prognosis
      of gastric cancer. Precancerous lesions of gastric carcinoma (PLGC) is a class of
      gastric cancer which is closely related to the gastric mucosal pathology changes
      in the role of carcinogenic incentives, and plays key role in the progression of
      normal gastric mucosal cells into gastric cancerous cells. In current experiment,
      we explore the relationship between Chinese traditional medicine (Xiao Tan He Wei
      Decoction) and gastric cancer in the PLGC rat animal models and epithelial
      mesenchymal transitioned GES-1 cells which were induced useing 1- Methyl-3-nitro
      1-nitrosoguanidine (MNNG). PLGC rat model showed significant deterioration in the
      gastric mucosa with terrible growth rate in body weight and more atypical
      hyperplasia in gastric mucosa. MC cells, MNNG induced GES-1 cells which
      epithelial- mesenchymal-transition (EMT)-related proteins have a great change
      compare with normal GES-1 cells. The cells had characteristics of malignant cells
      including proliferation, invasion and metastasis ability. Our research founds
      that Xiao Tan He Wei Decoction could inhibit cell proliferation and increased
      apoptosis by increase the level of pro-apoptotic proteins like Bax and caspase-3
      and decreased the level of anti-apoptotic protein Bcl-2, block the cells in G0/G1
      phase simultaneously. Furthermore, Xiao Tan He Wei Decoction could inhibit
      nuclear factor kappa-light-chain-enhancer (NF-kB) activity and inhibit its
      transfer from the cytoplasm to the nucleus. However, when we incubated with NF
      kappaB activator PMA, the effect of Xiao Tan He Wei Decoction was reversed. These
      results suggested that Xiao Tan He Wei Decoction could be used as a method for
      the treatment of gastric precancerous lesions, and possibly provide a theoretical
      basis for the clinical treatment of gastric cancer and gastric precancerous
      lesions.

PMID- 30218865
TI  - When is myocarditis indeed the cause of death? Reply to R.B. Dettmeyer, J. Lang,
      and C.G. Birngruber.

PMID- 30218864
TI  - Tobacco use during cannabis cessation: Use patterns and impact on abstinence in a
      National Drug Abuse Treatment Clinical Trials Network study.
AB  - BACKGROUND: It is common for cannabis users to also use tobacco. While data
      suggest that tobacco users have more difficulty achieving cannabis cessation,
      secondary analyses of clinical trial data sets may provide insight into the
      moderating variables contributing to this relationship, as well as changes in
      tobacco use during cannabis treatment. Those were the aims of this secondary
      analysis. METHODS: The parent study was a multi-site trial of N-acetylcysteine
      for cannabis dependence conducted within the National Drug Abuse Treatment
      Clinical Trials Network. Participants were treatment-seeking adults (ages 18-50)
      who met criteria for cannabis dependence (N = 302). For cigarette smokers (n =
      117), tobacco use was assessed via timeline follow-back and nicotine dependence
      was assessed via the Fagerstrom Test for Nicotine Dependence (FTND). Outcome
      measures included: 1) changes in tobacco use based on treatment assignment,
      nicotine dependence, and concurrent cannabis reduction/abstinence, and 2)
      independent associations between nicotine dependence and cannabis abstinence.
      RESULTS: Cigarette smokers accounted for 39% of the sample (117/302), with a
      median FTND score of 3.0 (10-point scale). Among those with lower baseline
      nicotine dependence scores, cigarette smoking was reduced in the active treatment
      group compared to placebo. Those with moderate/high levels of nicotine dependence
      showed slight increases in smoking following active treatment. Nicotine
      dependence did not affect cannabis cessation. CONCLUSIONS: Cigarette smoking
      during cannabis treatment was affected, but depended on baseline nicotine
      dependence severity, though dependence levels did not impact cannabis abstinence.
      Interventions that address both tobacco and cannabis are needed, especially due
      to an increasing prevalence of cannabis use.

PMID- 30218866
TI  - Gammahydroxybutyrate in hair of non-GHB and repeated GHB users: A new and
      optimized method.
AB  - Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid used recreationally
      as a drug of abuse due its strong suppressive effect on the central nervous
      system. The detection window of GHB in blood and urine is very narrow
      (t1/2=30min) but can be substantially prolonged using alternative matrices such
      as hair. We here present a newly developed and limited validated method with a
      solid phase extraction (SPE) using GC-MS/MS to determine concentrations of GHB in
      hair samples. The soft extraction technique (water and 90min ultrasonic bath)
      preserves GHB with a high yield and clean extracts. In addition, endogenous GHB
      can be detected in hair of non-GHB users. However, little is known about GHB
      concentrations in hair of abstinent, frequent and chronic GHB users. Therefore,
      we present data from hair samples of healthy volunteers to evaluate the proposed
      endogenous GHB ranges, and from GHB-dependent patients to address GHB
      concentrations in hair with GHB intake. In 20 non-GHB users, a mean endogenous
      concentration of 1.1+/-0.6ng/mg hair (range of 0.3-2ng/mg) was found. In GHB
      dependent patients, concentrations between 6.3-239.6ng/mg hair were found, with
      no correlation between concentrations in hair and dose of GHB intake. In summary,
      we present a new and limited validated method, adequately sensitive for the
      detection of GHB in hair, as well as first-time measurements of GHB
      concentrations in dependent patients in order to better understand the
      relationship between the frequency of use/dose and concentrations observed in
      hair samples.

PMID- 30218867
TI  - Rifle bullet deflection through a soft tissue simulant.
AB  - Trajectory deflections of 5.56 NATO and 7.62*39mm rifle bullets, fired through
      7.5, 15 and 22.5cm of gelatine, were studied. The magnitude of the deflections
      from the bullets' original trajectories after perforation are related to the
      length and the profile of the (wound) channels through gelatine. After 7.5cm of
      penetration depth, deflection was less than 1 degrees . With the longer channel
      lengths, bullet instability set in and subsequently, deflection was much larger.
      Deflection was highest with fragmented 5.56 NATO bullets after perforating 22.5cm
      of gelatine. The data from this study can be used to assess the degree of bullet
      deflection in trajectory reconstructions after incidents where human bodies were
      perforated with rifle bullets of the respective calibres and cartridge types.

PMID- 30218868
TI  - Proactive drugs in DFSA cases: Toxicological findings in an eight-years study.
AB  - In case of drug-facilitated sexual assault (DFSA), the evidence is frequently
      anecdotal, with few investigations based on scientific evidences being carried
      out and thus most cases are diagnosed as an acute drug or alcohol intoxication.
      The reason may lay in the lack of specific knowledge by the victim on the
      possibility to retrospectively study the allegedly events and to the absence of
      standardized and shared protocols among health, forensic and police subjects. On
      this basis, in 2015 the Unit of Forensic Toxicology of University of Florence and
      the Sexual Assaults Centre in Hospital Careggi have fixed a common protocol to be
      applied in case of DFSA. The purpose of the study was to describe the results of
      the application of the shared protocol for toxicological findings among women
      seeking health care after sexual assault, and to assess the relationship with so
      called proactive DFSA drugs. We conducted a study on female patients above 18
      years of age consulting the Sexual Assault Centre between 2010 and July 2018.
      Among the 256 patients included, 37.1% was positive at least for a substance.
      Alcohol was the most detected substance (57 cases), followed by Cannabis (19
      cases), cocaine (15 cases) and opiates/methadone (heroine: 5; morphine:1;
      methadone: 6); benzodiazepines and amphetamine were found in 13 and in 2 cases,
      respectively. Only case of gamma-hydroxybutyrate (GHB) consumption was observed
      while new psychoactive substances were not detected. Among the patients
      suspecting proactive DFSA, sedative drug findings, not explained by voluntary
      intake, were encountered.

PMID- 30218869
TI  - Transcriptional effects of polyethylene microplastics ingestion in developing
      zebrafish (Danio rerio).
AB  - Over the last few decades, plastic waste has become an increasing environmental
      concern as it accumulates in every environment on our planet. Though
      traditionally seen as a macroscopic problem (i.e., large plastic debris), plastic
      pollution is also evident at smaller scales. Indeed, the intentional industrial
      production of small plastic particles and the physical degradation of larger
      plastic debris have overtime resulted in an increased environmental prevalence of
      smaller plastic particles, including microplastics. While the effects of these
      small polymers on marine biota have been an important research focus, recent
      global surveys indicate that our freshwater lakes and rivers are also plagued by
      microplastics. However, despite these discoveries we currently have a limited
      understanding of the impact these particles may have on freshwater animals,
      particularly on vertebrate species. Thus, the aim of the present study was to
      assess the impact of high concentrations of microplastics (5 and 20 mg.L-1) on
      the early life stages in zebrafish, a model freshwater vertebrate model. To do
      this, we exposed embryonic and larval zebrafish to fluorescently labelled
      polyethylene microspheres for up to 14 days and assessed their microplastic
      content, growth, hatching and oxygen consumption rates. We then explored the
      molecular underpinnings of the microplastic response by RNA sequencing. Over the
      course of the exposure, we observed a consistent accumulation of microplastics in
      the gastrointestinal tract of the fish in a concentration dependent manner, but
      could not detect any detrimental effects of these particles on larval
      development, growth or metabolism. However, whole animal transcriptomics revealed
      that microplastics induced a transient and extensive change in larval gene
      expression within 48 h exposure, which largely disappeared by 14 days. However,
      as these transcriptional changes occurred during a critical period of larval
      development, we suggest that an evaluation of the potential long-term impact of
      these particles is warranted.

PMID- 30218870
TI  - Integrated assessment of heavy metal pollution using transplanted mussels in
      eastern Guangdong, China.
AB  - Heavy metal contamination has been widely studied in coastal areas around the
      world. However, integrative studies of heavy metals pollution by monitoring and
      characterizing sediments, organisms, and biomarkers as well as their holistic
      interactions are rare. Here, we selected a developed coastal area in eastern
      Guangdong, China as the study field. Heavy metal analysis (both in sediment and
      mussel) and biomarker tests, including neutral red retention time test (NRRT) and
      micronuclei (MN) test, were employed in the current research. Anthropogenic
      activities influenced the heavy metal levels in sediments. Significant
      relationships (p < 0.05) were observed in the concentrations of Cd, Cu, and Zn
      between sediments and transplanted mussel, and significant relationships (p <
      0.05) were also observed in between the concentrations of Cd, Cu, and Zn in
      sediments and the NRRT of mussel. The potential ecological risk index (RI) of
      sediments significantly correlated with NRRT (R = -0.991, p < 0.05). In Hao
      River, where the highest RI of sediments was found, the highest MN frequency and
      the lowest NRRT in mussels were detected simultaneously. The results indicated
      that the heavy metal pollution might cause subcellular toxic and genotoxic
      effects on mussels, especially for those from polluted areas (i.e., Hao River).
      The present study suggests that the transplanted green-lipped mussels are
      suitable for assessing heavy metal pollution, especially for Cd, Cu, and Zn.

PMID- 30218871
TI  - Mercury and lead exposure in avian scavengers from the Pacific Northwest suggest
      risks to California condors: Implications for reintroduction and recovery.
AB  - Mercury (Hg) and lead (Pb) are widespread contaminants that pose risks to avian
      scavengers. In fact, Pb exposure is the primary factor limiting population
      recovery in the endangered California condor (Gymnogyps californianus) and Hg can
      impair avian reproduction at environmentally relevant exposures. The Pacific
      Northwest region of the US was historically part of the condor's native range,
      and efforts are underway to expand recovery into this area. To identify potential
      threats to reintroduced condors we assessed foraging habitats, Hg and Pb
      exposure, and physiological responses in two surrogate avian scavenger species
      (common ravens [Corvus corax] and turkey vultures [Cathartes aura] across the
      region between 2012 and 2016. Mercury exposure near the Pacific coast was 17-27
      fold higher than in inland areas, and stable carbon and sulfur isotopes ratios
      indicated that coastal scavengers were highly reliant on marine prey. In
      contrast, Pb concentrations were uniformly elevated across the region, with 18%
      of the birds exposed to subclinical poisoning levels. Elevated Pb concentrations
      were associated with lower delta-aminolevulinic acid dehydratase (delta-ALAD)
      activity, and in ravens there was an interactive effect between Hg and Pb on
      fecal corticosterone concentrations. This interaction indicated that the effects
      of Hg and Pb exposure on the stress axis are bidirectional, and depend on the
      magnitude of simultaneous exposure to the other contaminant. Our results suggest
      that condors released to the Pacific Northwest may be exposed to both elevated Hg
      and Pb, posing challenges to management of future condor populations in the
      Pacific Northwest. Developing a robust monitoring program for reintroduced
      condors and surrogate scavengers will help both better understand the drivers of
      exposure and predict the likelihood of impaired health. These findings provide a
      strong foundation for such an effort, providing resource managers with valuable
      information to help mitigate potential risks.

PMID- 30218872
TI  - Removal of hexavalent chromium from groundwater by Mg/Al-layered double
      hydroxides using characteristics of in-situ synthesis.
AB  - This study aimed to develop a novel in-situ method to directly remove toxic
      hexavalent chromium anions from groundwater. The characteristics of Mg/Al-layered
      double hydroxides (LDH) involving in-situ synthesis and interlayer exchangeable
      anions can facilitate to remove Cr(VI) from solution. Two different methods of
      LDH preparation were employed to explore the adsorption efficiency of
      (di)chromates, such as traditional coprecipitation (CO3-LDH) and innovative in
      situ synthesis (in-situ-LDH). The synthesized LDH samples were characterized
      using scanning electron microscopy, X-ray diffraction, Fourier transform infrared
      spectroscopy, X-ray photoelectron spectroscopy, and zeta potential. The results
      demonstrated that the adsorptive amount of Cr(VI) for the in-situ synthesis
      process dramatically increased with an increase in initial Cr(VI) concentrations
      from 100 mg/L to 900 mg/L. The kinetic study indicated that the constant rate
      (k2) of the pseudo-second-order equation significantly decreased when the initial
      concentration of Cr(VI) exceeded 500 mg/L. The removal efficiency of Cr(VI) was
      slightly dependent on solution pH (5.0-12) values. The in-situ-LDH absorbent (339
      mg/g) exhibited the significantly higher Langmuir maximum adsorption capacity
      than CO3-LDH (246 mg/g). The primary adsorption mechanism was anion exchange;
      meanwhile, the adsorption-coupled reduction mechanism also played an integral
      role. The advanced in-situ synthetic method can be developed to efficiently
      remove toxic hexavalent chromium anions from groundwater.

PMID- 30218873
TI  - The addition of citrate stimulates the production of acetoin and diacetyl by a
      citrate-positive Lactobacillus crustorum strain during wheat sourdough
      fermentation.
AB  - In traditional sourdough fermentation recipes of artisan bakeries, often extra
      ingredients are added to the flour-water mixture. This may accentuate the aroma
      and taste of the baked products produced from such sourdoughs. This is made
      possible, for instance, by stimulating certain microbial activities during
      fermentation. This study examined the effects of the addition of citrate (a food
      grade organic acid present in milk and lemons) on wheat sourdough fermentation in
      the presence of a citrate-positive, homofermentative, lactic acid bacterial
      starter culture strain, namely Lactobacillus crustorum LMG 23699. Both liquid and
      firm wheat sourdoughs were produced. The starter culture strain was able to steer
      all wheat sourdough fermentations performed, as it always prevailed due to its
      competitiveness, as shown through culture-dependent microbiological plating and
      culture-independent bacterial community profiling. Moreover, it possessed all
      enzyme-encoding genes (as unraveled through genome mining) necessary to convert
      citrate into desirable compounds such as lactic acid, acetic acid, succinate,
      acetoin, diacetyl, and 2,3-butanediol. Indeed, citrate addition to the wheat
      flour-water mixture had an impact on the sourdough fermentation dynamics and thus
      on the aroma profile of the liquid and firm sourdoughs produced and breads made
      thereof. A higher final pH, higher total titratable acidity values, and low yeast
      counts were found in wheat sourdoughs produced with citrate. In particular, the
      starter culture strain added converted the supplemented citrate into more l
      lactic acid as well as acetoin and diacetyl (buttery aroma compounds), which was
      independent of the dough yield. The buttery aroma compounds were also accentuated
      in the concomitant breads produced. Further, organic acid production was
      stimulated in the sourdoughs, whereas increased pyrazine concentrations occurred
      in the breads. Consequently, citrate supplementation to wheat sourdoughs could be
      of interest to produce baked goods with enhanced buttery aroma compounds and
      notes.

PMID- 30218874
TI  - n-butylparaben exposure during perinatal period impairs fertility of the F1
      generation female rats.
AB  - Parabens are a class of preservatives widely used in the majority of personal
      care products, cosmetics, medicines, and food products. However, current
      literature suggests its plausible role as an endocrine disruptor, hence the
      present study was undertaken to delineate the effects of n-butyl paraben on
      perinatally exposed F1 female rats. F0 dams were exposed subcutaneously to n
      butylparaben from gestation day 6 (GD 6) to postnatal day (PND) 21 with doses of
      10, 100, and 1000 mg/kg Bw/day in corn oil. The F1 female rats were monitored for
      pubertal development and sexual maturation through PND 30, 45, and 75; which were
      subsequently subjected to fertility assessment at PND 75. Perinatal exposure to n
      butylparaben resulted in- This study documents impaired steroidogenesis and
      folliculogenesis might be the prime reason for the reduced fertility of F1 female
      rats. Hence, our study suggests that health monitors need to counsel potential
      females planning for pregnancy to avoid exposure to parabens.

PMID- 30218875
TI  - Accumulation of chemical elements in yellow-necked mice under a colony of great
      cormorants.
AB  - This study represents the first investigation into the accumulation of chemical
      elements in small mammals inhabiting the territory of a great cormorant colony.
      Trapping was done in the Juodkrante great cormorant colony, one of the largest
      colonies in Europe. The accumulation of 20 chemical elements in the bodies
      (muscle and bones) of yellow-necked mice (Apodemus flavicollis) was investigated
      using the energy-dispersive x-ray fluorescence equipment Spectro Xepos HE. Two
      groups of positively inter-correlated chemical elements (Mg, Al, P, Ca and Al, S,
      Cl, K) were identified. The concentrations of five elements differed
      significantly between mice trapped in different zones of the colony with
      differing intensities of cormorant influence: the values of K and Cu in A.
      flavicollis increased in line with an increase in the influence of the
      cormorants, while the concentrations of Rb and Pb decreased. The concentrations
      of Mn differed between zones, but were not related to the intensity of bird
      influence. Differences in the concentration of Zn (ANOVA F = 24.38; p < 0.001),
      Fe (F = 4.60; p < 0.05) and Mo (F = 4.47; p < 0.05) were related to the gender
      factor, all concentrations being higher in females. The concentrations of Zn were
      age-dependent, being highest in adult individuals (21.7 +/- 4.5 MUg g-1) and
      exceeding those in subadult (19.4 +/- 3.4 MUg g-1) individuals or juveniles (16.7
      +/- 1.3 MUg g-1). In general, the concentrations of accumulated elements in A.
      flavicollis from the territory of the cormorant colony were lower than in rodents
      from industrially polluted sites.

PMID- 30218876
TI  - Cr(VI) removal using different reducing agents combined with fly ash leachate: A
      comparative study of their efficiency and potential mechanisms.
AB  - Remediation of high concentrations of Cr(VI) in wastewater involves its chemical
      reduction to Cr(III), a product with low toxicity that can be easily removed. To
      date, NaBH4 has rarely been used to reduce Cr(VI). This article reports a
      comparative study of Cr(VI) removal by NaBH4 and five sulfur-based reducing
      agents (FeSO4, Na2S2O5, NaHSO3, Na2S2O3, and Na2SO3). The potential mechanisms of
      Cr(VI) removal by these six reducing agents with and without fly ash leachate
      (FAL) are also discussed. The results revealed that the reduction and subsequent
      removal of Cr(VI) are influenced by the hydrolysis and ionization of the reducing
      agents in solution. Thus, the reduction reaction was significantly enhanced when
      Na2S2O5 and NaHSO3 were added in excess of 600 mg L-1. Combined with FAL, smaller
      amounts of NaBH4 were required to reduce Cr(VI) to Cr(III) at pH 3.0 compared to
      those with the other reducing agents. NaBH4 combined with FAL at a dose of 100 mg
      L-1 afforded a total Cr (CrT) removal of 96.32% within 20 min, a value much
      higher than that obtained with the other reducing agents. The catalytic mechanism
      of NaBH4 for such a FAL-catalyzed Cr(VI) reduction system is similar to that of
      acid catalysis via the hydrolysis of the Fe(III) and Al(III) species in FAL.
      Improvement of the CrT removal was also observed via Cr(VI) entrapment in the
      structure of Fe(III) and Al(III) metal hydroxides. These results indicate that
      relatively low loadings of NaBH4 combined with FAL show great promise for Cr(VI)
      pollution remediation.

PMID- 30218877
TI  - Neurodevelopmental toxicity induced by maternal PM2.5 exposure and protective
      effects of quercetin and Vitamin C.
AB  - Epidemiological studies show that maternal exposure to PM2.5 affects the
      neurodevelopment of the offspring, especially the neurocognitive function.
      However, no relevant experimental researches have been published on toxic
      mechanism and diet intervention. We evaluated the effects of exposure to
      different doses of PM2.5 on the behavioral development of offspring via a PM2.5
      exposure model established by intratracheal instillation, explored its mechanism
      and the protective effects of quercetin and VC intervention, and focused on the
      protein expression of CREB/BDNF signaling pathway. Specifically, Exposure to
      PM2.5 during gestation and lactation period caused maternal oxidative stress.
      Maternal exposure to PM2.5 changed postnatal open-field behaviors in both gender,
      impaired spatial learning and memory in the female offspring, increased the level
      of IL-1beta, IL-6, down-regulated p-CREB/CREB, BDNF, TrkB, p-CaMKII/CaMKII, p
      CaMKIV/CaMKIV, up-regulated p-Akt/Akt and p-ERK1/2/ERK1/2 in the offspring. In
      addition, maternal supplementation with quercetin ameliorate the maternal
      oxidative stress, improved progeny inflammatory response, regulated BDNF, TrkB, p
      Akt/Akt, p-ERK1/2/ERK1/2 in female offspring, regulated TrkB, p-CREB/CREB and p
      Akt/Akt in male offspring. Maternal supplementation with VC increased the levels
      of CAT in maternal mice, up-regulated BDNF in female offspring, regulated p
      CREB/CREB and p-ERK1/2/ERK1/2 in male offspring. Our findings indicate that PM2.5
      exposure during pregnancy and lactation could impair behavioral development of
      offspring. Quercetin shows more protective effects than VC. The mechanism of
      neurodevelopmental toxicity induced by PM2.5 may be related to oxidative stress,
      inflammatory response and modulation of the CREB/BDNF signaling pathway.

PMID- 30218878
TI  - Predictive value of early MRI findings on neurocognitive and psychiatric outcomes
      in patients with severe traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) is the major public health problem
      worldwide, particularly in the Middle East. Diffuse axonal injury (DAI) is
      commonly found in TBI. Although DAI can lead to physical and psychosocial
      disabilities, its prognostic value is still a matter of debate. Magnetic
      Resonance (MR) is more sensitive for detecting DAI lesions. OBJECTIVE: To
      identify the radiological and clinical factors associated with the functional
      capacity one year after the traumatic brain injury. METHODS: The study included
      251 patients with severe head trauma for whom Brain MRI was done within one month
      after injury. Demographic, clinical, and radiological data were collected during
      hospitalization. Neurocognitive and psychiatric evaluation were done one year
      thereafter. RESULTS: DAI was more frequent in our patients. Psychiatric
      disorders, cognitive impairment, and poor functional outcome were more common in
      patients with DAI especially those with cerebral hemisphere and brain stem
      lesion, and mixed lesions. Duration of post traumatic amnesia (DPTA), lost
      consciousness and hospital stay (DHS) as well as the volume of diffuse axonal
      injury (DAI) were associated with poor neurocognitive outcome. DPTA, and DAIV may
      be considered independent factors that could predict the neurocognitive outcome.
      CONCLUSION: MRI following traumatic brain injury yields important prognostic
      information, with several lesion patterns significantly associated with poor long
      term neurocognitive and psychiatric outcomes.

PMID- 30218879
TI  - Predictors of distal malfunction after ventriculoperitoneal shunting for
      idiopathic normal pressure hydrocephalus and effect of general surgery
      involvement.
AB  - OBJECTIVES: Distal obstruction is a common cause of shunt failure and need for
      revision in patients undergoing ventriculoperitoneal shunting (VPS) for
      idiopathic normal pressure hydrocephalus (iNPH). PATIENTS AND METHODS: Records of
      patients with iNPH treated with VPS between 2001 and 2017 were reviewed. Patients
      undergoing initial shunt placement at our institution were included for analysis
      and the incidence of revision surgery due to distal obstruction was noted. Risk
      factors for distal obstruction were identified using a stepwise Cox proportional
      hazards model. RESULTS: There were 341 patients included for analysis. Assistance
      from a general surgeon in placement of the peritoneal catheter was provided in 54
      patients (15.8%). Shunt revision was necessary in 69 patients (20.2%), with 17
      patients (5.0%) found to have a distal malfunction. On univariate analysis,
      increasing age was associated with reduced risk of distal malfunction (Unit RR
      0.92, 95% CI 0.89-0.96; p < 0.001). BMI >= 38.9 (RR 6.60, 95% CI 1.84-19.00),
      prior abdominal surgery (RR 2.95, 95% CI 1.11-7.70; p = 0.032), and fixed-setting
      valve (RR 6.24, 95% CI 1.27-112.72; p = 0.020) were associated with increased
      likelihood of distal malfunction. General surgery involvement had no effect on
      distal malfunction rates (OR 1.30, 95% CI 0.25-3.21; p = 0.693). On multivariate
      analysis, increasing age (Unit RR 0.92, 95% CI 0.89-0.95; p < 0.001) and prior
      abdominal surgery (RR 3.30, 95% CI 1.23-8.71; p = 0.019) were independently
      associated with decreased and increased risk of distal obstruction, respectively.
      CONCLUSIONS: We identify multiple factors associated with distal shunt
      obstruction, and found that general surgery assistance was not protective against
      distal malfunction. These data may aid in the risk-stratification of patients
      undergoing VPS for iNPH.

PMID- 30218880
TI  - Anatomical evaluation of the vertebral artery (V2) and its influence in cervical
      spine surgery.
AB  - OBJECTIVE: The aim of this study was to quantitatively evaluate the surgical
      anatomy of the vertebral artery and the sub-axial spine to assess their influence
      on cervical spine surgery. PATIENTS AND METHODS: Retrospective data was evaluated
      from a total of 275 three-dimensional head and neck CT-angiograms. Vertebral
      artery diameter (VAD) and the distance between the uncinate process superior
      ridge and vertebral artery (UPVD) were measured. The minimum pedicle transverse
      angles (miPTAs), maximum PTA (MxPTAs), pedicle width (PW) and range of PTA (rPTA)
      were also measured. RESULT: The mean value of the right UPVD was larger than that
      on the left: 4.5 vs. 3.6 mm (C3), 3.4 vs. 2.8 mm (C4), 3.0 vs. 2.5 mm (C5) and
      3.1 vs. 2.4 mm (C6), respectively. The mean value of miPTA (32.2 vs. 31.7 degrees
      : C3, 36.9 vs. 35.2 degrees : C4, 35.3 vs. 33.9 degrees : C5 and 29.9 vs. 29.2
      degrees : C6) and MxPTA (56 vs. 55.6 degrees : C3, 61.7 vs. 60 degrees : C4, 60.3
      vs. 58.5 degrees : C5 and 54.9 vs. 55 degrees : C6) showed no statistical
      significance of laterality. The mean value of PW and rPTA ranged between 5.0-5.8
      mm and 23.8-25.8 degrees  on both sides. CONCLUSIONS: Generally, right and mid-
      cervical segment decompression was found to be more secure than that on the left
      and in the lower cervical segment during an anterior cervical approach,
      considering the values of VAD and UPVD. Results of this study indicate that more
      attention should be paid to the mid-cervical pedicle screw fixation regarding the
      miPTA value, and rPTA (23.9-25.8 degrees ) should be maintained constantly
      regardless of cervical segment.

PMID- 30218881
TI  - Relationship between neck motion and self-reported pain in patients with whiplash
      associated disorders during the acute phase.
AB  - BACKGROUND: Biomechanical measures quantify motor control and functional deficits
      in Whiplash Associated Disorders (WAD), but few studies relate those measures to
      the clinical scales that are routinely used to assess patients. Most studies are
      limited to chronic neck pain, and report poor to moderate correlations.
      OBJECTIVE: To define a statistical model that relates measures of neck kinematics
      with clinical scales of neck pain, in WAD patients during the rehabilitation
      process in the acute phase (less than 3 months since the accident). METHODS: 96
      WAD patients self-assessed their pain using VAS and NPQ, and passed neck motion
      tests as part of their rehabilitation program. Four regression models were fitted
      to analyze the effects of the measured kinematic parameters and subject-specific
      characteristics on VAS and NPQ. Model errors were compared to minimal clinically
      significant differences. RESULTS: Multiple correlation coefficients of the models
      were between 0.74 and 0.90. More than 66% of that correlation was accounted for
      by subject-specific factors, and most of the other half by the measured kinematic
      parameters. Range of motion of flexion-extension and axial rotation, and
      harmonicity of flexion-extension, where the variables most consistently related
      to the decrease of pain. The error of the models was within the MCSD in more than
      50% of the observations. CONCLUSIONS: Part of the individual progression of pain
      and pain-related disability in acute WAD patients, as rated by NPQ and VAS, can
      be mapped to objective kinematic parameters of neck mobility tests, like ranges
      of motion, velocities, repeatability and harmonicity of movements.

PMID- 30218883
TI  - Sphenopalatine ganglion block in combination with greater and lesser occipital
      nerve blocks for the management of post dural puncture headache.

PMID- 30218882
TI  - Physiotherapist-delivered Stress Inoculation Training for acute whiplash
      associated disorders: A qualitative study of perceptions and experiences.
AB  - BACKGROUND: Formally trained and accredited physiotherapists delivered Stress
      Inoculation Training (SIT) integrated with guideline-based physiotherapy
      management to individuals with acute whiplash associated disorders (WAD) as part
      of a randomised controlled trial. The delivery of SIT by physiotherapists is new.
      OBJECTIVES: To investigate physiotherapists' perspectives on delivering SIT as
      part of the trial and in routine practice. DESIGN: Qualitative descriptive.
      METHOD: Physiotherapists (n = 11) participated in semi-structured interviews.
      Interviews were audio-recorded, transcribed verbatim, and analysed thematically.
      Findings were triangulated against an audit of physiotherapists' adherence to the
      SIT protocol. RESULTS: Three themes were identified: perceived value; capacity to
      deliver; and adaptation and implementation. Physiotherapists' saw value in SIT in
      that they perceived the program to have improved patient outcomes, enhanced their
      therapeutic alliance, and provided new skills to manage psychological
      contributors to WAD. Physiotherapists' capacity to deliver the program was
      facilitated through the development of confidence in their ability to deliver
      sessions, viewing SIT as falling within their current professional identity, and
      having confidence in their ability to manage mismatches in patients' expectations
      of care. All physiotherapists reported having used SIT to some extent in routine
      practice, by selectively delivering sessions and/or integrating the content with
      other management. Physiotherapists were able to deliver SIT as was intended
      (94.6% adherence). CONCLUSIONS: Physiotherapists' supported adding SIT to usual
      management of individuals with acute WAD. Education on SIT principles is
      recommended during pre-professional training to facilitate future implementation.

PMID- 30218884
TI  - Postoperative outcomes with neuraxial versus general anesthesia in bilateral
      total hip arthroplasty.
AB  - STUDY OBJECTIVE: Current evidence remains limited on the postoperative outcomes
      of neuraxial (NA) versus general anesthesia (GA) as primary anesthesia type in
      patients receiving simultaneous bilateral total hip arthroplasty (BTHA). We aimed
      to evaluate the rates of postoperative outcomes among patients receiving NA
      versus GA for BTHA. DESIGN: Retrospective cohort study. SETTING: Multi
      institutional. PATIENTS: A total of 798 patients undergoing BTHA with 519 and 279
      who received GA and NA, respectively. We used the American College of Surgeons -
      National Surgical Quality Improvement Program database for years 2007 to 2016.
      INTERVENTIONS: Patients undergoing BTHA. MEASUREMENTS: We propensity-score
      matched on demographic factors and comorbid conditions to compare rates of
      postoperative outcomes among cohorts (NA versus GA). We performed Pearson chi
      square and Wilcoxon rank sum test to compare NA versus GA cohorts. MAIN RESULTS:
      The final analysis included 798 BTHA patients, of which 35% received NA as the
      primary anesthetic. The median age was 58 years old and 50.8% were female. The
      rate of perioperative transfusion in the NA and GA group were 20.1% and 29.0%,
      respectively (p = 0.02). There were no significant differences in the rate of
      postoperative outcomes between patients receiving NA versus GA as their primary
      anesthesia type (Bonferroni corrected p < 0.006 was considered statistically
      significant). CONCLUSION: Our study showed no significant differences in
      postoperative outcomes between NA versus GA following BTHA. Further studies are
      needed to investigate outcomes among this surgical population.

PMID- 30218885
TI  - Anesthetic management of an infant with Jeune syndrome and severe pulmonary
      hypertension for tracheostomy.

PMID- 30218886
TI  - Spinal anesthesia with a low dosage of local anesthetic for urgent cesarean
      delivery in a parturient with Klippel-Feil syndrome.

PMID- 30218887
TI  - Modification of surgical approach and cannulation strategy for mitral valve
      repair after intraoperative diagnosis of persistent left superior vena cava.

PMID- 30218888
TI  - Rigid dinuclear ruthenium-arene complexes showing strong DNA interactions.
AB  - Six novel dinuclear Ru(II)-arene complexes [Ru2(eta6-p-cymene)2(1,3
      bib)2Cl2]*2.Solvent (X = Cl- (1), I- (2), NO3- (3), BF4- (4), PF6- (5), CF3SO3-
      (6); 1,3-bib = 1,3-di(1H-imidazol-1-yl) benzene) were synthesized and fully
      characterized by FT-IR, 1H NMR, ESI-MS, Elemental Analysis (EA) and Powder X-ray
      Diffraction (PXRD). Single crystal X-ray diffractions studies showed that 3 and 4
      have rigid bowl-like structures, where one counter-anion (NO3- for 3 and BF4- for
      4) was trapped inside the cavity to balance the charge, respectively. Even
      complexes 1-6 showed only moderate or little anti-proliferative activity toward
      cancer cells, strong interactions with DNA molecules through intercalation,
      however, were confirmed by UV-Vis, CD and fluorescence spectroscopy. Apoptosis
      and cell cycle arrest studies for complex 2 with cancer A549 cells indicated
      concentration-dependent late apoptosis and the G1/G0 phase arrest. Interactions
      with the tripeptide glutathione (gamma-L-Glu-L-Cys-Gly, GSH) might explain the
      relatively low antiproliferative potency of these complexes. This class of rigid
      dinuclear cations hold potential as DNA-targeting anticancer agents if their
      uptake and delivery could be under controlled.

PMID- 30218889
TI  - Study on the detoxification mechanisms to 5,10,15,20-tetrakis (4-sulfonatophenyl)
      porphyrinato iron(III) chloride (FeTPPS), an efficient pro-oxidant of heme water
      soluble analogue.
AB  - 5,10,15,20-Tetrakis (4-sulfonatophenyl) porphyrinato iron(III) chloride (FeTPPS)
      is a water-soluble analog of heme and widely employed as peroxynitrite scavenger
      in vivo. However, previous studies have showed that like heme, FeTPPS could also
      act as an effective pro-oxidant towards appreciable substrates in vitro in the
      presence of oxidant. The reason that FeTPPS did not show any pro-oxidative damage
      in previous studies when it was used as peroxynitrite decomposition catalyst in
      vivo, has not been studied. Herein, the effects of two main detoxification
      mechanisms of heme, i.e., serum albumin (SA) binding and heme oxygenase-1 (HO-1)
      induction, were examined on FeTPPS in vitro. Fluorescence quenching studies
      showed bovine serum albumin (BSA) could bind to FeTPPS with high affinity (Kb ~
      109 M-1). Molecular docking studies presented us the details of the binding site
      that is not a heme pocket. Furthermore, the intrinsic pro-oxidative activity of
      FeTPPS was found effectively inhibited by forming BSA-FeTPPS complex of low
      reactivity, which could be thought to protect against the potentially toxic
      effects of FeTPPS on blood components. In addition, this binding could protect
      FeTPPS against oxidative degradation. In albumin-free cell system, cell viability
      results indicated FeTPPS was innoxious to living cells and could protect cells
      against the oxidative impairment of H2O2 effectively rather than promoting
      damage. Using western blot, we illustrated that HO-1 expression could not be
      induced by FeTPPS, which suggested that HO-1 was not related to the protective
      capacity of FeTPPS. Our results provide a better understanding of FeTPPS and lead
      to a new guidance to its application.

PMID- 30218890
TI  - Zeise's salt as powerful platinating agent for proteins investigated by top-down
      mass spectrometry.
AB  - Metallodrugs have become an integral part of modern medicinal chemistry with
      platinum drugs as anti-cancer agents being well-known examples. The historically
      interesting compound Zeise's salt, potassium trichlorido(ethene)platinate(II) has
      scarcely been investigated in this context yet. This study is geared towards
      shedding light on the biological reactivity of this platinum complex. Mass
      Spectrometry tools were used to obtain a deeper understanding of its interactions
      with biomolecules on the molecular level. Angiotensin I and Ubiquitin were chosen
      as model systems. Comparison to Cisplatin show that Zeise's salt is more reactive
      towards nucleophilic sites in proteins. Our data indicate that the ethylene
      ligand remains on the platinum when coordinated to a nitrogen donor in the
      biomolecule and therefore offers a linkage for the introduction of further
      functionality. When attached to sulfur donors in the biomolecule, platinum(II)
      provides a site for the formation of crosslinks and loops in the biomolecules by
      losing all four of its initial ligands.

PMID- 30218891
TI  - Risk stratification of cervical disease using detection of human papillomavirus
      (HPV) E4 protein and cellular MCM protein in clinical liquid based cytology
      samples.
AB  - BACKGROUND: While human papillomavirus (HPV) DNA testing offers high sensitivity
      for the detection of significant cervical disease, its specificity is suboptimal
      given the high prevalence of transient HPV infections (CIN1 or less). Biomarkers
      to identify those suffering from low grade disease from those with high grade
      disease could save healthcare costs and reduce patient anxiety. OBJECTIVE: The
      objective of the present work was to develop and test an immunohistochemistry
      (IHC)-based dual viral and cellular biomarker strategy which was applicable to
      liquid based cytology (LBC) samples. STUDY DESIGN: We developed a novel IHC assay
      for detection of HPV E4 and cellular minichromosome maintenance (MCM) proteins in
      routinely taken cervical LBC samples using cytospin-prepared slides. The assay
      was applied to a prospective cohort of Scottish women referred to a colposcopy
      clinic due to preceding cytological abnormalities. The performance of the
      biomarkers for detection of clinically insignificant (CIN1 or less) versus
      significant disease was determined. RESULTS: A total of 81 women were recruited
      representing 64 cases of <=CIN1 and 28 of CIN2 + . Biomarker performance relative
      to histopathology outcomes showed high levels of MCM detection was significantly
      associated with CIN2+ (p = 0.03) while E4 was detected more frequently in <=CIN1
      (p = 0.06). CONCLUSIONS: Combined detection of a host proliferation marker and a
      marker of viral gene expression could allow triage of cases of clinically
      insignificant disease prior to colposcopy. However, there was overlap between
      distributions of MCM levels in CIN2+ and <=CIN1 suggesting that additional
      biomarkers would be required for improved specificity. Combined with cytospin
      prepared slides this approach could provide a means of risk stratification of
      disease in low resource settings.

PMID- 30218892
TI  - Association between plasma CD36 levels and incident risk of coronary heart
      disease among Danish men and women.
AB  - BACKGROUND AND AIMS: CD36 is a cholesterol receptor involved in the uptake of
      oxidized low-density lipoprotein cholesterol and development of atherosclerotic
      plaques. Cross-sectional studies have shown correlations between plasma CD36 and
      atherosclerosis but no prospective study has examined the association yet. We
      prospectively examined the association between plasma CD36 levels and risk of
      incident coronary heart disease (CHD) in a Danish population. METHODS: Plasma
      CD36 levels were measured in a case-cohort study nested within the Danish
      population-based cohort, the Diet, Cancer and Health Study. A total of 1963
      incident CHD events occurred between baseline (1993-1997) and 2008, and a sub
      cohort of 1759 participants were randomly selected as reference. Cox proportional
      hazard regression models were used to compute the hazard ratio (HR) and
      corresponding 95% confidence interval (CI). RESULTS: After adjusting for CHD risk
      factors, including history of hypercholesterolemia and diabetes, elevated plasma
      CD36 levels were not associated with higher CHD risk in the total population, and
      the HR comparing the highest versus lowest tertile of CD36 levels was 1.02 (95%
      CI: 0.84-1.23). High CD36 levels were only found to be associated with risk of
      CHD in combination with prevalent diabetes (HR = 2.83, 95% CI: 1.08-7.45) vs. the
      joint reference group of lowest CD36 tertile and no diabetes. CONCLUSIONS: Plasma
      CD36 levels were not predictive of CHD risk in the general population.

PMID- 30218893
TI  - Human interaction in the NICU and its association with outcomes on the Brief
      Infant-Toddler Social and Emotional Assessment (BITSEA).
AB  - BACKGROUND: Extremely preterm infants represent one of the highest risk
      categories for impairments in social competence. Few studies have explored the
      impact of the neonatal intensive care unit (NICU) environment on social
      development. However, none have specifically analyzed the effects of the care
      structure the infant receives during hospitalization on later social competence
      indicators. OBJECTIVE: To identify associations between the care structures
      received by extremely preterm infants in the NICU and scores on the Brief Infant
      Toddler Social and Emotional Assessment (BITSEA) post-discharge. PARTICIPANTS: 50
      extremely preterm infants (mean gestational age: 25 weeks during hospitalization;
      mean chronological age during follow-up assessment: 2 years, 4 months). METHODS:
      A secondary analysis of BITSEA data was performed exploring its relation to care
      structure data we extracted from electronic medical records (i.e., how much time
      infants were engaged in human interaction during their first thirty days of
      hospitalization and what types of interaction they were exposed to). RESULTS:
      Extremely preterm infants spend a considerable amount of time alone during
      hospitalization (80%) with nursing care comprising the majority of human
      interaction. Infants who experienced greater human interaction scored
      significantly higher on the Social Competence (p = 0.01) and lower on the
      Dysregulation (p = 0.03) BITSEA subscales. CONCLUSION: Human interaction and
      isolation in the NICU is associated with social competence and dysregulation
      outcomes in extremely preterm infants. Further research is needed to understand
      how various NICU care structures including centralized nursing teams, parental
      skin-to-skin care, and early therapy may synergistically play a positive role in
      developing social competence.

PMID- 30218894
TI  - Effect of post-anthesis waterlogging on biosynthesis and granule size
      distribution of starch in wheat grains.
AB  - Waterlogging is one of the most common abiotic stress types in wheat production
      in many rainy areas of the world. Two locally widely grown winter wheat (Triticum
      aestivum L. cv Yumai 34 and Yangmai 9) were subjected to post-anthesis
      waterlogging in a pot experiment to investigate the impacts of waterlogging on
      the starch synthesis and the physiochemical properties. Post-anthesis
      waterlogging significantly decreased grain weight and affected the content of
      starch components. Waterlogging down-regulated the activity and expression of
      genes encoding soluble starch synthase [SSS (EC 2.4.1.21)], while up-regulated
      those of the granule bound starch synthase I [GBSSI (EC:2.4.1.242)]. This further
      resulted in decreased amylopectin content and increased amylose content.
      Waterlogging also caused a reduction in the number of starch granules, while
      increased the mean diameter of starch granules in mature grains, which was mainly
      due to an increase in the volume frequency percent of the A-type starch granules.
      Waterlogging also lowered the peak viscosity and trough viscosity of starch, but
      did not affect the breakdown viscosity and peak time. We concluded that the
      modified expressions of the starch synthase encoding genes were responsible for
      the changed size distribution of starch granules, which finally affected the
      starch pasting properties of wheat growing under post-anthesis waterlogging
      conditions.

PMID- 30218895
TI  - A complete workflow for the differentiation and the dissociation of hiPSC-derived
      cardiospheres.
AB  - Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are
      an invaluable tool for both basic and translational cardiovascular research. The
      potential that these cells hold for therapy, disease modeling and drug discovery
      is hampered by several bottlenecks that currently limit both the yield and the
      efficiency of cardiac induction. Here, we present a complete workflow for the
      production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This
      includes the efficient and highly reproducible differentiation of hiPSCs into
      cardiospheres, which display enhanced physiological maturation compared to static
      3D induction in hanging drops, and a novel papain-based dissociation method that
      offers higher yield and viability than the broadly used dissociation reagents
      TrypLE and Accutase. Molecular and functional analyses of the cardiomyocytes
      reseeded after dissociation confirmed both the identity and the functionality of
      the cells, which can be used in downstream applications, either as monolayers or
      spheroids.

PMID- 30218896
TI  - Copy number variations in healthy subjects. Case study: iPSC line CSSi005-A
      (3544) production from an individual with variation in 15q13.3 chromosome
      duplicating gene CHRNA7.
AB  - CHRNA7, encoding the neuronal alpha7 nicotinic acetylcholine receptor (a7nAChR),
      is highly expressed in the brain, particularly in the hippocampus. It is situated
      in the 15q13.3 chromosome region, frequently associated with a Copy Number
      Variation (CNV), which causes its duplication or deletion. The clinical
      significance of CHRNA7 duplications is unknown so far, but there are several
      research data suggesting that they may be pathogenic, with reduced penetrance. We
      have produced an iPS cell line from a single healthy donor's fibroblasts carrying
      a 15q13.3 CNV, including CHRNA7 in order to study the exact role of this CNV
      during the neurodevelopment.

PMID- 30218897
TI  - Simulations of ultrasonic wave propagation in concrete based on a two-dimensional
      numerical model validated analytically and experimentally.
AB  - Several non-destructive evaluation techniques to characterize concrete structures
      are based on ultrasonic wave propagation. The interpretation of the results is
      often limited by the scattering phenomena between the ultrasonic wave and the
      high concentration aggregates contained in the cement matrix. Numerical
      simulations allow for further insights. This study aims to build a two
      dimensional numerical model in order to reproduce and interpret ultrasonic wave
      propagations in concrete. The model is built in a spectral-element software
      package called SPECFEM2D. The validation of the numerical tool is based on the
      use of resin samples containing different amount of aluminum rods from low (5%)
      to high concentration (40%), the last one being representative of aggregate
      concentration in concrete. These samples are characterized using an ultrasonic
      testing bench (ultrasonic water tank) from 150 kHz to 370 kHz. The measured
      results are analyzed in terms of phase velocity and attenuation which are the
      main parameters of coherent waves. As homogenization models such as the Waterman
      Truell or Conoir-Norris models are usually used to model coherent waves in two
      phase systems, we also compare the experimental and numerical results against
      them. We confirm that the use of these homogenization models is limited to low
      concentration of scattering phase, which is not adapted to applications to
      concrete. Finally, we use our numerical tool to carry out a parametric study on
      scatterer concentration, shape, orientation and size distribution of aggregates
      in concrete. We show that aggregate orientation has an influence on coherent wave
      parameters, but aggregate shape has not.

PMID- 30218898
TI  - Characterization of piezoelectric wafer active sensor for acoustic emission
      sensing.
AB  - In this article, a new avenue of using the piezoelectric wafer active sensor
      (PWAS) for detecting the fatigue crack generated acoustic emission (AE) signals
      is presented. In-situ AE-fatigue experiments were conducted using PWAS along with
      two commercially available AE sensors. It has been shown that the PWAS and
      existing AE sensors successfully captured the AE signals from the fatigue crack
      growth in a thin aerospace specimen. Two experiments were conducted using the
      PWAS with each of the commercial AE sensors. For each experiment, two AE analyses
      were performed: (1) the hit-based analysis, (2) the waveform-based analysis. The
      fatigue loading was synchronized with the AE measurements. This allowed comparing
      the AE hits due to a particular AE event captured by PWAS and the other sensors.
      All the sensors showed a very similar pattern of AE hits as observed from the hit
      based analysis. The AE waveform-based analysis was used to compare the waveforms
      and their frequency spectra captured by the three sensors. The commercial PICO
      showed ringing in the AE signals and showed a weak response in high-frequency
      region. The commercial S9225 had better signal-to-noise ratio but it also showed
      a weak response in high-frequency region. It was found that all sensors captured
      the low-frequency flexural modes of the guided acoustic waves. However, the high
      frequency acoustic wave signals were predominately captured by the PWAS. The AE
      waveform-based analysis provided more insight of the AE source and guided wave
      propagation modes.

PMID- 30218899
TI  - Imaging fast electrical activity in the brain during ictal epileptiform
      discharges with electrical impedance tomography.
AB  - Electrical Impedance Tomography (EIT) is an emerging medical imaging technique
      which can produce tomographic images of internal impedance changes within an
      object using non-penetrating surface electrodes. It has previously been used to
      image impedance changes due to neuronal depolarisation during evoked potentials
      in the rat somatosensory cortex with a resolution of 2 ms and <200 MUm, using an
      epicortical electrode array. The purpose of this work was to use this technique
      to elucidate the intracortical spatiotemporal trajectory of ictal spike-and-wave
      discharges (SWDs), induced by electrical stimulation in an acute rat model of
      epilepsy, throughout the cerebral cortex. Seizures lasting 16.5 +/- 5.3 s with
      repetitive 2-5 Hz SWDs were induced in five rats anaesthetised with fentanyl
      isoflurane. Transfer impedance measurements were obtained during each seizure
      with a 57-electrode epicortical array by applying 50 MUA current at 1.7 kHz to
      two electrodes and recording voltages from all remaining electrodes. Images were
      reconstructed from averaged SWD-related impedance traces obtained from EIT
      measurements in successive seizures. We report the occurrence of reproducible
      impedance changes during the initial spike phase, which had an early onset in the
      whisker barrel cortex and spread posteriorly, laterally and ventrally over 20 ms
      (p < 0.03125, N = 5). These findings, which confirm and extend knowledge of SWD
      initiation and expression, suggest that EIT is a valuable neuroimaging tool for
      improving understanding of neural circuits implicated in epileptic phenomena.

PMID- 30218901
TI  - Rheological characteristics of faecal sludge from VIP latrines and implications
      on pit emptying.
AB  - This work aims at characterizing the rheological properties of faecal sludge from
      Ventilated Improved Pit (VIP) latrines and their implication on pit emptying.
      Faecal sludge was sampled from 3 pit latrines located in the eThekwini
      Municipality (Durban, South Africa). Samples were taken at different positions
      within the pit. For each of the samples, measurements in the rheometer in
      triplicates were performed in order to determine their rheological properties,
      and their moisture and ash content were measured also in triplicates. Experiments
      in the rheometer were performed for samples for which its moisture content was
      modified. In order to better understand the influence of water addition into the
      pit. During pit emptying, calculations were carried out from the experimental
      data, based in the criteria set in the Omni-Ingestor initiative, carried out by
      the Bill & Melinda Gates Foundation. Faecal sludge exhibited a shear thinning
      behaviour, i.e. a decrease in viscosity with increasing shear rate, and presented
      a yield stress comprised between 500 to 1000 Pa. This needs to be surpassed in
      order to overcome the elastic resistance of the sludge to flow. Similar
      viscosities were found for the samples from the different pits, irrespective of
      the position within the pit, except for the sample from the bottom of one of the
      pits for which it was not possible to induce a flow. This sample had a
      considerably lower moisture content (67% wet basis) compared to the other samples
      (around 80% wet basis), probably due to a higher biodegradation as it was the
      most aged sludge in the pit. According to the experimental results and
      calculations, the pumping requirements during pit emptying will decrease
      drastically by increasing the moisture content of the sludge. The addition of
      water into the pit would then facilitate the pit emptying operation by reducing
      the head and power required for pumping. However, this practice would require
      employing considerable amounts of water and handling higher volumes of sludge,
      which would lead to longer pit emptying times and increase the difficulty of the
      operation. For example, increasing the moisture content of the sludge from 75 to
      90% will reduce the head and power of the pump by a factor 100, but will
      triplicate the amount of water in the sludge and, consequently, the time for pit
      emptying. Therefore, a compromise has to be made between increasing the pumping
      feasibility and adding water to the pit.

PMID- 30218902
TI  - The effect on ozone catalytic performance of prepared-FeOOH by different
      precursors.
AB  - In this study, different precursors were used to prepare FeOOH and the ozonation
      catalytic activity was s investigate by using ibuprofen as the degradation
      substrate. It could be found that FeOOH prepared from ferric sulfate performed
      higher activity. Subsequently, the catalysts were characterized by X-ray
      diffraction, Fourier transform infrared spectrometer, scanning electron
      microscope and N2 adsorption-desorption techniques. X-ray diffraction and Fourier
      transform infrared spectrometer showed that the synthesized FeOOH consisted of
      alpha-FeOOH and beta-FeOOH mainly. Scanning electron microscope showed that their
      appearance and morphology were significantly different, and the FeOOH prepared
      from ferric sulfate had a larger specific surface area, resulting in its better
      catalytic activity. Finally, the hydroxyl groups and pHzpc of the catalyst
      surface were measured. It was also found that the FeOOH prepared from ferric
      sulfate owned more hydroxyl groups and the pHzpc of the surface was closer to the
      pH of the degradation substrate, which illustrated the reasons for the increased
      catalytic activity. In addition, the degradation kinetics conformed to the pseudo
      first-order kinetic model and the hydroxyl radicals played an important role in
      the reaction process.

PMID- 30218900
TI  - Morphometric MRI as a diagnostic biomarker of frontotemporal dementia: A
      systematic review to determine clinical applicability.
AB  - Frontotemporal dementia (FTD) is difficult to diagnose, due to its heterogeneous
      nature and overlap in symptoms with primary psychiatric disorders. Brain MRI for
      atrophy is a key biomarker but lacks sensitivity in the early stage. Morphometric
      MRI-based measures and machine learning techniques are a promising tool to
      improve diagnostic accuracy. Our aim was to review the current state of the
      literature using morphometric MRI to classify FTD and assess its applicability
      for clinical practice. A search was completed using Pubmed and PsychInfo of
      studies which conducted a classification of subjects with FTD from non-FTD
      (controls or another disorder) using morphometric MRI metrics on an individual
      level, using single or combined approaches. 28 relevant articles were included
      and systematically reviewed following PRISMA guidelines. The studies were
      categorized based on the type of FTD subjects included and the group(s) against
      which they were classified. Studies varied considerably in subject selection, MRI
      methodology, and classification approach, and results are highly heterogeneous.
      Overall many studies indicate good diagnostic accuracy, with higher performance
      when differentiating FTD from controls (highest result was accuracy of 100%) than
      other dementias (highest result was AUC of 0.874). Very few machine learning
      algorithms have been tested in prospective replication. In conclusion,
      morphometric MRI with machine learning shows potential as an early diagnostic
      biomarker of FTD, however studies which use rigorous methodology and validate
      findings in an independent real-life cohort are necessary before this method can
      be recommended for use clinically.

PMID- 30218903
TI  - Delamination of plastic-coated waste paper by enzymes of the white rot fungus
      Dichomitus squalens.
AB  - Many paper products are coated with plastic to improve their quality and
      stability. However, this limits recycling and recovery options and the plastic
      coated waste paper is mostly disposed in landfills. Such practices are
      uneconomical and contrary to sustainable waste management. In this work enzymes
      of the white rot fungus Dichomitus squalens were investigated for possible
      delamination of plastic-coated waste paper. Enzymes were found capable to release
      the polyethylene foil from plastic-coated paper which resulted in 88.6-91.5% mass
      loss. The delamination rate, however, was depended on the ratio between plastic
      coated paper and volume of enzyme filtrate. Results of a consequent experiment
      showed that enzymes are also efficient when plastic-coated paper is treated in a
      sequencing batch reactor resulting in 88.2-90.6% mass loss. The system was fully
      functional up to the 5th cycle; afterwards, the delamination rate reduced due to
      high thickness of the waste paper sludge. The enzyme activity, however, was still
      very high; with the laccase activity at the end of the experiment above 900 U/L
      and manganese peroxidase above 250 U/L. Our results demonstrated, that plastic
      coated waste paper has the potential to be efficiently recovered instead of being
      disposed in landfills.

PMID- 30218904
TI  - Performance of various catalysts on treatment of refractory pollutants in
      industrial wastewater by catalytic wet air oxidation: A review.
AB  - The tremendous increase of industrialization and urbanization worldwide causes
      the depletion of natural resources such as water and air which urges the
      necessity to follow the environmental sustainability across the globe. This
      requires eco-friendly and economical technologies for depollution of wastewater
      and gases or zero emission approach. Therefore, in this context the treatment and
      reuse of wastewater is an environmental friendly approach due to shortage of
      fresh water. Catalytic wet air oxidation (CWAO) is a promising technology for the
      treatment of toxic and non-biodegradable organic pollutants in the wastewater
      generated from various industries. Various heterogeneous catalysts have been
      extensively used for treatment of various model pollutants such as phenols,
      carboxylic acids, nitrogenous compounds and different types of industrial
      effluents. The present review focuses on the literature published on the
      performances of various noble and non-noble metal catalysts for the treatment of
      various pollutants by CWAO. Reports on biodegradability enhancement of industrial
      wastewater containing toxic contaminants by CWAO are reviewed. Detailed
      discussion is made on catalyst deactivation and their mitigation study and also
      on the various factors which affects the CWAO reaction.

PMID- 30218905
TI  - Active control of acoustics-caused nano-vibration in atomic force microscope
      imaging.
AB  - In this paper, we propose a finite-impulse-response (FIR)-based feedforward
      control approach to mitigate the acoustic-caused probe vibration during atomic
      force microscope (AFM) imaging. Compensation for the acoustic-caused probe
      vibration is important, as environmental disturbances including acoustic noise
      induce nano-scale probe vibration, directly affecting the AFM performance in
      applications such as imaging, nanomechanical characterization, and
      nanomanipulation. Although conventional passive noise cancellation apparatus has
      been employed, limitation exists, and residual noise still persists. Thus, a FIR
      based active feedforward control approach is developed, by exploring a data
      driven approach to account for the vibrational dynamics of the probe caused by
      the environmental acoustic noise in the controller design. An experimental
      implementation in AFM imaging application is presented and discussed to
      illustrate the proposed technique. Experimental results show that the FIR-based
      feedforward control is promising to not only complement, but also alleviate the
      limitations of passive noise control in AFM operations.

PMID- 30218906
TI  - Long-term performance of biological ion exchange for the removal of natural
      organic matter and ammonia from surface waters.
AB  - Anionic exchange is an effective treatment option for the removal of natural
      organic matter from surface waters. However, the management of the spent brine
      regenerant often limits the adoption of this process. The current study reports
      one year of operation of ion exchange resins under biological mode (BIEX, i.e.
      without regeneration to promote biofilm growth on the media) compared to the
      performance of (i) ion exchange with weekly regeneration (IEX), (ii) granular
      activated carbon under biological mode (BAC) and (ii) granular activated carbon
      under adsorption mode (GAC). Four parallel pilot filters (GAC, BAC, IEX and BIEX)
      were fed with a colored and turbid river water without pretreatment. Although IEX
      provided the best performance (80% DOC removal) throughout the study, BIEX
      achieved a similar performance to IEX prior to DOC breakthrough (92 days) and
      subsequently achieved a mean DOC removal of 62% in warm water conditions. The GAC
      filter was rapidly exhausted (2 weeks) while the BAC filter only provided a 5%
      DOC reduction. Full nitrification was observed on both the BIEX and BAC filters
      under warm water conditions (>15  degrees C). After one year of operation, BIEX
      was successfully regenerated with brine. According to a mass balance, 69% of DOC
      removal in BIEX was due to ion exchange while we assume the remainder was
      biodegraded. Operation of ion exchange in biological mode is a promising option
      to reduce spent brine production while still achieving high DOC removal.

PMID- 30218907
TI  - Enhancement of anaerobic digestion sludge dewatering performance using in-situ
      crystallization in combination with cationic organic polymers flocculation.
AB  - Anaerobic digestion (AD) has been widely used in sludge treatment for biogas
      recovery, organic fraction stabilization, and sludge reduction. However, after
      AD, sludge filterability is extremely deteriorated due to the release of
      biopolymers and the formation of fine particles. AD sludge is generally rich in
      nutrients, mainly ammonium nitrogen and phosphates, that result from biopolymer
      degradation. We designed a conditioning process that combines the in-situ
      crystallization of magnesium ammonium phosphate (MAP), as a skeleton builder,
      with organic polymer flocculation. We show that crystallized MAP can bind with
      extracellular polymeric substance fractions to increase sludge floc density. The
      molecular structure and electrical charge of organic polymers importantly
      influence sludge particle flocculation and aggregation. We found that cationic
      polyacrylamides form flocs that aggregate with branching structures which are
      characterized by a larger size and a more compact structure. Simultaneous
      crystallization and flocculation produced by a magnesium-organic polymer gel
      improved AD dewaterability more than the separate addition of magnesium ions and
      organic polymers. The method of sludge conditioning that we propose was tested by
      extensive use in different AD sludge conditioning protocols. The method reduces
      the ammonium nitrogen load in AD liquor and increases the suitability of the
      biosolids for use as land fertilizer.

PMID- 30218908
TI  - Molecular design, synthesis and biological evaluation of cage compound-based
      inhibitors of hepatitis C virus p7 ion channels.
AB  - The hepatitis C caused by the hepatitis C virus (HCV) is an acute and/or chronic
      liver disease ranging in severity from a mild brief ailment to a serious lifelong
      illness that affects up to 3% of the world population and imposes significant and
      increasing social, economic, and humanistic burden. Over the past decade, its
      treatment was revolutionized by the development and introduction into clinical
      practice of the direct acting antiviral (DAA) agents targeting the non-structural
      viral proteins NS3/4A, NS5A, and NS5B. However, the current treatment options
      still have important limitations, thus, the development of new classes of DAAs
      acting on different viral targets and having better pharmacological profile is
      highly desirable. The hepatitis C virus p7 viroporin is a relatively small
      hydrophobic oligomeric viral ion channel that plays a critical role during virus
      assembly and maturation, making it an attractive and validated target for the
      development of the cage compound-based inhibitors. Using the homology modeling,
      molecular dynamics, and molecular docking techniques, we have built a
      representative set of models of the hepatitis C virus p7 ion channels (Gt1a,
      Gt1b, Gt1b_L20F, Gt2a, and Gt2b), analyzed the inhibitor binding sites, and
      identified a number of potential broad-spectrum inhibitor structures targeting
      them. For one promising compound, the binding to these targets was additionally
      confirmed and the binding modes and probable mechanisms of action were clarified
      by the molecular dynamics simulations. A number of compounds were synthesized,
      and the tests of their antiviral activity (using the BVDV model) and cytotoxicity
      demonstrate their potential therapeutic usefulness and encourage further more
      detailed studies. The proposed approach is also suitable for the design of broad
      spectrum ligands interacting with other multiple labile targets including various
      viroporins.

PMID- 30218909
TI  - Synthesis of 5H-pyrido[3,2-b]pyrrolizin-5-one tripentone analogs with antitumor
      activity.
AB  - Pyrrolizinones represent an interesting class of compounds with varied degrees of
      structural complexity and pharmacological activity. Among these, 9H-pyrido[2,3
      b]pyrrolizin-9-one, tripentone analogs, recently reported by us, showed
      significant antiproliferative activity against human tumor cell lines, inducing
      apoptosis and not affecting viability of Caco-2 differentiated in normal
      intestinal-like cells. Considering their interesting biological activity, their
      5H-pyrido[3,2-b]pyrrolizin-5-one analogs were efficiently synthesized in good to
      excellent yields (61-91%). All tripentone derivatives were tested to assess their
      cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal
      carcinoma) and MCF-7 (human breast cancer). The most active derivatives, with
      IC50 ranging from 0.11 to 16.11 MUM, did not affect viability of Caco-2
      differentiated in normal intestinal-like cells, suggesting tumor cells as the
      main target of their cytotoxic action. The same compounds, further investigated,
      showed that they did not exert necrotic effects, while induced a clear shift of
      viable cells towards early apoptosis confining the cells in the mitotic phases.

PMID- 30218910
TI  - Synthesis and antibacterial activity evaluation of novel biaryloxazolidinone
      analogues containing a hydrazone moiety as promising antibacterial agents.
AB  - A series of linezolid analogues containing a hydrazone moiety were designed,
      synthesized and evaluated for their antibacterial activity. Most compounds
      exhibited more potent antibacterial activity against S.aureus, MRSA, MSSA, LREF
      and VRE pathogens as compared with linezolid and radezolid. Compounds 9a, 9c, 9f,
      9g, 10m and 10t were more potent against tested clinical isolates of MRSA, MSSA,
      VRE and LREF as compared to linezolid. Compound 9a exhibited comparable activity
      with linezolid against human MAO-A for safety evaluation and showed moderate
      metabolism in human liver microsome. The most promising compound 9a showed
      remarkable antibacterial activity against S.aureus, MRSA, MSSA, LREF and VRE
      pathogens with MIC value of 0.0675 mg/mL, respectively, which was 15- to 30-fold
      more potent than linezolid.

PMID- 30218911
TI  - Systematic variation of the benzoylhydrazine moiety of the GluN2A selective NMDA
      receptor antagonist TCN-201.
AB  - GluN2A containing N-methyl-D-aspartate receptors (NMDARs) are important ion
      channels in the central nervous system and highly involved in several different
      neurophysiological but also neuropathophysiological processes. However, current
      understanding of the contribution of GluN2A containing NMDARs in these processes
      is incomplete. Therefore, highly selective compounds are required to further
      investigate these ion channels. In 2010, TCN-201 (2), one of the first selective
      negative allosteric modulators was reported. While the binding site of 2 and the
      influence of the substitution pattern of the benzenesulfonamide part has been
      reported recently, detailed structure-activity-relationships of the
      diacylhydrazine part and the linked phenyl moiety are still missing. In order to
      examine the critical interactions between these moieties and the binding site,
      several TCN-201 analogs with modified diacylhydrazine part were synthesized. The
      negative allosteric effect was recorded by two-electrode voltage clamp (TEVC)
      experiments using GluN1a/GluN2A expressing Xenopus laevis oocytes. Our data led
      to the conclusion, that the terminal phenyl moiety is involved in a cation-pi
      interaction with the guanidinium moiety of Arg755 of the GluN1a subunit, which
      plays a crucial role for high activity. Additionally, structure optimization by
      replacing the phenyl moiety with a thiophen-2-yl (10c), indol-2-yl (10g) or indol
      3-yl (10h) moiety significantly increased the activity of 2 by the factor 2.5. At
      a test compound concentration of 200 nM, the negative allosteric effect of the
      most potent ligands 10c, 10h and 17 was significantly influenced by the glycine
      concentration. Although glycine dependency is higher than those of the lead
      compound 4, 10c and 17 showed significantly higher negative allosteric effects
      than 4 at glycine concentrations from 1 MUM up to 10 MUM. The potent GluN2A-NMDA
      receptor inhibitors 10c, 10h and 17 did not influence the ion current of GluN2B
      NMDA receptors.

PMID- 30218912
TI  - Systematicity, but not compositionality: Examining the emergence of linguistic
      structure in children and adults using iterated learning.
AB  - Recent work suggests that cultural transmission can lead to the emergence of
      linguistic structure as speakers' weak individual biases become amplified through
      iterated learning. However, to date no published study has demonstrated a similar
      emergence of linguistic structure in children. The lack of evidence from child
      learners constitutes a problematic gap in the literature: if such learning biases
      impact the emergence of linguistic structure, they should also be found in
      children, who are the primary learners in real-life language transmission.
      However, children may differ from adults in their biases given age-related
      differences in general cognitive skills. Moreover, adults' performance on
      iterated learning tasks may reflect existing (and explicit) linguistic biases,
      partially undermining the generality of the results. Examining children's
      performance can also help evaluate contrasting predictions about their role in
      emerging languages: do children play a larger or smaller role than adults in the
      creation of structure? Here, we report a series of four iterated artificial
      language learning studies (based on Kirby, Cornish & Smith, 2008) with both
      children and adults, using a novel child-friendly paradigm. Our results show that
      linguistic structure does not emerge more readily in children compared to adults,
      and that adults are overall better in both language learning and in creating
      linguistic structure. When languages could become underspecified (by allowing
      homonyms), children and adults were similar in developing consistent mappings
      between meanings and signals in the form of structured ambiguities. However, when
      homonimity was not allowed, only adults created compositional structure. This
      study is a first step in using iterated language learning paradigms to explore
      child-adult differences. It provides the first demonstration that cultural
      transmission has a different effect on the languages produced by children and
      adults: While children were able to develop systematicity, their languages did
      not show compositionality. We focus on the relation between learning and
      structure creation as a possible explanation for our findings and discuss
      implications for children's role in the emergence of linguistic structure.

PMID- 30218913
TI  - Working memory training and perceptual discrimination training impact overlapping
      and distinct neurocognitive processes: Evidence from event-related potentials and
      transfer of training gains.
AB  - There is emerging evidence that working memory (WM) can potentially be enhanced
      via targeted training protocols. However, the differential effects of targeted
      training of WM vs. training of general attentional processes on distinct
      neurocognitive mechanisms is not well understood. In the present study, we
      compared adaptive n-back WM training to an adaptive visual search training task
      that targeted perceptual discrimination, in the absence of demands on WM. The
      search task was closely matched to the n-back task on difficulty and participant
      engagement. The training duration for both protocols was 20 sessions over
      approximately 4 weeks. Before and after training, young adult participants were
      tested on a battery of cognitive tasks to examine transfer of training gains to
      untrained tests of WM, processing speed, cognitive control, and fluid
      intelligence. Event-related brain potential (ERP) measures obtained during a
      Letter 3-Back task and a Search task were examined to determine the neural
      processes that were affected by each training protocol. Both groups improved on
      measures of cognitive control and fluid intelligence at post- compared to
      pretest. However, n-back training resulted in more pronounced transfer effects to
      tasks involving WM compared to search training. With respect to ERPs, both groups
      exhibited enhancement of P3 amplitude following training, but distinct changes in
      neural responses were also observed for the two training protocols. The search
      training group exhibited earlier ERP latencies at post- compared to pretest on
      the Search task, indicating generalized improvement in processing speed. The n
      back group exhibited a pronounced enhancement and earlier latency of the N2 ERP
      component on the Letter 3-back task, following training. Given the theoretical
      underpinnings of the N2, this finding was interpreted as an enhancement of
      conflict monitoring and sequential mismatch identification. The findings provide
      evidence that n-back training enhances distinct neural processes underlying
      executive aspects of WM.

PMID- 30218914
TI  - Critical features for face recognition.
AB  - Face recognition is a computationally challenging task that humans perform
      effortlessly. Nonetheless, this remarkable ability is better for familiar faces
      than unfamiliar faces. To account for humans' superior ability to recognize
      familiar faces, current theories suggest that different features are used for the
      representation of familiar and unfamiliar faces. In the current study, we applied
      a reverse engineering approach to reveal which facial features are critical for
      familiar face recognition. In contrast to current views, we discovered that the
      same subset of features that are used for matching unfamiliar faces, are also
      used for matching as well as recognition of familiar faces. We further show that
      these features are also used by a deep neural network face recognition algorithm.
      We therefore propose a new framework that assumes similar perceptual
      representation for all faces and integrates cognition and perception to account
      for humans' superior recognition of familiar faces.

PMID- 30218915
TI  - Safe sex norm questionnaire for female sex workers: development and validation
      study in Iran.
AB  - OBJECTIVES: The aim of the present study was to develop and validate a safe sex
      norm questionnaire as an appropriate instrument which would be adaptable to the
      female sex worker (FSW) population. STUDY DESIGN: A mixed method study. METHODS:
      Appropriate content was prepared through a literature review. Content validation
      indices were assessed using interviews with content experts and lay experts. A
      conservative approach was used to assess the inter-rater agreement among the
      participants about the instrument relevance and clarity. The scale content
      validity index was computed using the average method. Non-parametric Mokken scale
      analysis was used for assessing scalability and unidimensionality of the
      questionnaire in a sample of 170 FSWs in Tehran. To evaluate the reliability and
      internal consistency of the questionnaire intra-class correlation and Cronbach's
      alpha were employed. RESULTS: A list of 34 items was finalized, with subscales
      for actual behavioral norms and for perceived norms. The relevance of the actual
      and perceived norms subscales in the final questionnaire was higher than 96%;
      clarity of the subtests was 99% and higher. The comprehensiveness of the actual
      and perceived norms subscales was 85% for both. Mokken scale analysis showed that
      the two subscales were distinct constructs, and all items are good indicators for
      the constructs. CONCLUSION: Our findings support that the safe sex norm
      questionnaire is a valid and reliable measure that would be useful to harm
      reduction programs and help effective HIV prevention among female sex workers.

PMID- 30218916
TI  - Corrigendum to "Induction of oxidative stress by long-term treatment of live
      HEK293 cells with therapeutic concentration of lithium is associated with down
      regulation of delta-opioid receptor amount and function" [Biochem. Pharmacol. 154
      (2018) 452-463].

PMID- 30218917
TI  - Quantitation of plasma and urine 3-hydroxyglutaric acid, after separation from 2
      hydroxyglutaric acid and other compounds of similar ion transition, by liquid
      chromatography-tandem mass spectrometry for the confirmation of glutaric aciduria
      type 1.
AB  - BACKGROUND: Glutaric aciduria type 1, a deficiency of glutaryl-CoA dehydrogenase,
      causes an accumulation of neurotoxic metabolites glutaric acid and 3
      hydroxyglutaric acid (3-HGA). Testing of these analytes is routinely done by GC
      MS but seldom account for interference from isomers or compounds with similar ion
      transitions. We developed a liquid chromatography tandem mass spectrometry method
      that accurately measures 3-HGA in urine and plasma specimens, while utilizing
      similar reagents and instrumentation used for the routine performance of amino
      acid and acylcarnitine analysis in determining the diagnosis of several metabolic
      disorders. METHOD: Plasma and urine samples were added aliquots of the deuterated
      3-HGA internal standard and acetonitrile. The protein-free supernatant was
      brought to dryness, and the residue derivatized using 3 M HCL in 1-butanol with
      heating. The dried derivative was then reconstituted in 50% methanol-water
      solution and aliquot transferred to an HPLC vial for analysis by LC-MS/MS.
      Separation was performed using a C8 HPLC column under flow gradient conditions of
      0.2% formic acid in water and methanol, respectively. Ionization was by ESI and
      detection of selected precursor-product ion transitions by multiple reaction
      monitoring (MRM) in positive mode. RESULTS: The butyl-ester derivative of 3-HGA
      eluted at 7.82 min while 2-hydroxyglutaric acid (2-HGA) eluted at 8.21 min. This
      was equivalent to a separation factor of 1.05 and a resolution of 1.03,
      respectively. The 3-HGA calibration curve was linear over the range 6.20-319 ng
      mL-1 (r2 = 0.9996), and the reportable range determined by the linearity was
      found to be 1.54-384 ng mL-1. The calculated limits of detection and quantitation
      were 0.348 and 1.56 ng mL-1, respectively. Intra- and Inter-assay %CVs for
      quality control plasma and urine samples ranged from 2 to 18%, with recoveries of
      66-115%. The method correlated to the gold standard GC-MS method for both serum
      (r2 >= 0.996) and urine analysis (r2 >= 0.949). The concentration of 3-HGA in
      normal, non-GA1 individuals was <=25.2 ng mL-1 (in plasma) and <= 35.0 MUmol mmol
      1 of creatinine (in urine). CONCLUSIONS: This LC-MS/MS method accurately
      quantified plasma and urine 3-HGA concentration after successful resolution from
      2-HGA and other compounds with similar ion transitions. This method is suitable
      for confirmatory testing of 3-HGA, as a follow-up to an abnormal newborn screen
      test result, with concern for GA type 1.

PMID- 30218918
TI  - Separation of two microbial transglutaminase isomers from Streptomyces
      mobaraensis using pH-mediated cation exchange chromatography and their
      characterization.
AB  - Microbial transglutaminase (MTGase) derived from Streptomyces mobaraensis has
      been widely used in the food, biotechnology and medicine fields. The lot-to-lot
      consistency and product stability of MTGase must be ensured. The structure and
      charge variants of MTGase can influence its bioactivity. In this study, MTGase
      isomers (MTG I1 and MTG I2) were found during the separation of MTGase by pH
      mediated cation-exchange chromatography. MTG I1 and MTG I2 had the same molecular
      weight and N-terminal amino acid sequences, but they showed charge heterogeneity.
      The affinity of MTG I2 for substrates was higher than that of MTG I1, and the
      thermal stability and the acid-base tolerance of MTG I1 were significantly higher
      than that of MTG I2. Therefore, the ratio of MTG I1/MTG I2 was positively
      correlated with the stability of MTGase. The buffer pH and the ionic strength of
      the eluent had significant effects on the separation of MTG I1 and MTG I2, and
      the elution gradient steepness and column load showed little effect on the
      separation of the MTG I1 and MTG I2 peaks. We built a stable and repeatable
      separation method for MTG I1 and MTG I2. MTG I1 could transform into MTG I2, but
      MTG I2 was unable to transform into MTG I1, making the transformation of MTG I1
      to MTG I2 was irreversible. When MTG I2 was removed from the MTGase, a portion of
      the MTG I1 could transform into MTG I2. Therefore, one way to increase the
      stability of MTGase was to reduce the transformation of MTG I1 to MTG I2.

PMID- 30218920
TI  - Psychosocial factors associated with symptoms of depression, anxiety and stress
      among single mothers with young children: A population-based study.
AB  - BACKGROUND: Abundant evidence highlights single parenthood as a common risk
      factor for depression, anxiety and stress but few studies have comprehensively
      examined psychosocial factors (adversities), particularly during early parenting.
      We investigated symptom prevalence and potential risk factors among mothers with
      very young children. METHODS: Data stem from the 2015 National Psychosocial
      Burdens Prevalence Study (KiD 0-3). Mothers with children up to 3 years of age (n
      = 6925) were recruited from random probability-sampled paediatric clinics (n =
      271) across Germany and reported on depression or anxiety, general and parenting
      stress using the Patient Health Questionnaire (PHQ-4), Perceived Stress Scale
      (PSS-4) and Parenting Stress Index (PSI). Multivariable logistic regression
      models determined risk factors and quantified potential mediation of psychosocial
      factors for all 3 outcomes. RESULTS: Approximately 30% of single mothers (n =
      517) reported depressive or anxiety symptoms and 37% general stress, twice as
      high compared to partnered mothers (n = 6408; p < 0.0001). Parenting stress was
      also elevated (p < 0.0001). Adjusted regression models confirm that single
      mothers are twice as likely to report symptoms of depression or anxiety (OR 1.9,
      CI95% 1.4-2.5). Risk factors for stress correspond to those for depression and
      anxiety. Inadequate social support and history of partner or childhood
      maltreatment were also consistent risk factors across all outcomes. LIMITATIONS:
      The study design and self-reported symptoms are limitations to consider.
      CONCLUSIONS: Single mothers with young children are more predisposed to mental
      health disorders than partnered mothers, especially when facing financial, social
      or distal adversities. Appropriate social support programs and screening measures
      are necessary to reduce further disparities.

PMID- 30218919
TI  - Sensitive inexpensive chromatographic determination of an antimicrobial
      combination in human plasma and its pharmacokinetic application.
AB  - This study represents simple inexpensive chromatographic determination of
      ciprofloxacin (CIP) and tinidazole (TIN) simultaneously in human plasma using
      HPLC-DAD followed by a pharmacokinetic application. C18 column was used as
      stationary phase with isocratic elution of a mobile phase composed of acetic acid
      solution (2%) and acetonitrile (85: 15, v/v) and ornidazole as internal standard
      (IS) with UV detection at 318 nm. The two drugs and the IS were separated at
      6.55, 7.91 and 11.07 min for CIP, TIN and IS, respectively, with good selectivity
      and sensitivity for their analysis in presence of plasma matrix components and
      the drugs' metabolites. Sample preparation involved only protein precipitation
      without any complicated extraction procedures decreasing analysis time. For
      method validation, FDA regulations for analysis in biological fluids were
      followed. Pharmacokinetic (PK) study on six healthy volunteers was conducted
      after single oral dose administration of 500 and 600 mg of CIP and TIN,
      respectively. Dugs' plasma levels were followed for 12 or 72 h post dosing for
      CIP and TIN, respectively, and different PK data for the two drugs were
      calculated and they were comparable to the reported values demonstrating
      successful future application of the presented method in PK, bioequivalence and
      bioavailability studies.

PMID- 30218921
TI  - Milder forms of alpha-sarcoglicanopathies diagnosed in adulthood by NGS analysis.
AB  - INTRODUCTION: Sarcoglycanopathies (LGMD 2C2F) are a subgroup of limb-girdle
      muscular dystrophies (LGMD), caused by mutations in sarcoglycan genes. They
      usually have a childhood onset and rapidly progressive course with loss of
      ability to walk over 12-16 years. METHODS: Next generation sequencing (NGS)
      targeted gene panel was performed in three adult patients with progressive muscle
      weakness in which routine muscle histology and immunohistochemistry were not
      diagnostic. RESULTS: Genetic analysis revealed homozygous or compound
      heterozygous mutations in SGCA gene and Western Blot demonstrated protein
      reduction confirming the diagnosis of alpha-sarcoglicanopathy. DISCUSSION: Our
      cases evidence that the diagnosis of mild forms of alfa sarcoglicanopathy could
      be a challenge and suggest the possibility that they could be underdiagnosed. The
      use of Next generation Sequencing targeted gene panels is very helpful in the
      diagnosis of these patients.

PMID- 30218922
TI  - Risk of psychiatric disorders in Guillain-Barre syndrome.

PMID- 30218923
TI  - On the origin of the synergy between the Pt nanoparticles and MnO2 nanosheets in
      Wonton-like 3D nanozyme oxidase mimics.
AB  - We describe a 3-dimensional scaffold nanocomposite oxidase nanozyme (termed
      PtNPs@MnO2) formed from 2-dimensional MnO2 nanosheets grown on the surface of
      large platinum nanoparticles (PtNPs). The two components act synergistically in
      the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB), due to the
      intimate contact between the two components and mutual electron transfer
      phenomena. The Wonton-like 3-dimensional structure of the nanocomposite is highly
      stable and was characterized by cryogenic electron microscopy (cryo-EM). The
      PtNPs@MnO2 nanocomposite was employed in a sensing assay for the determination of
      glutathione (GSH) and dopamine (DA) with a linear range of 0.2 MUM-11 MUM for GSH
      and 0.1 MUM-1.1 MUM for DA. The limit of detection (LOD) and limit of
      quantification (LOQ) of GSH are 0.05 MUM (S/N = 3) and 0.17 MUM (S/N = 10),
      respectively. The LOD and LOQ for DA were estimated as 0.025 MUM and 0.083 MUM.
      The method was applied to analyze GSH in human serum samples and DA in
      pharmaceuticals.

PMID- 30218924
TI  - Hierarchical nanocomposites with an N-doped carbon shell and bimetal core: Novel
      enzyme nanocarriers for electrochemical pesticide detection.
AB  - Core-shell structured nanocomposites (named PtPd@NCS) with N-doped carbon shell
      and bimetal core (Pt and Pd) were fabricated through a facile strategy for the
      first time. The PtPd@NCS nanocomposites were obtained through reduction of
      K2PtCl4, H2PtCl6 and Na2PdCl4 species, self-polymerization of dopamine (DA) and
      co-assembly of Pluronic F127 using a one-pot approach. DA serves as a reductant,
      as well as a carbon and nitrogen source. The core-shell structure of the PtPd@NCS
      nanocomposites was characterized and the result indicated that Pt-Pd nanoparticle
      core with a diameter of approximately 15 nm was encased in the N-doped carbon
      shells with a thickness of approximately 35 nm. The PtPd@NCS nanocomposites were
      used as an electrode material to prepare acetylcholinesterase (AChE) biosensors
      for detecting organophosphate pesticides. The obtained AChE biosensor exhibited a
      linear range of 1 * 10-14 to 1 * 10-10 M and 1 * 10-9 to 1 * 10-5 M within the
      detection limit of 7.9 * 10-15 M for malathion, 1 * 10-13 to 1 * 10-6 within the
      detection limit of 7.1 * 10-14 M for chlopyrifos, and 1 * 10-14 to 1 * 10-11 M
      and 1 * 10-10 to 1 * 10-5 M within the detection limit of 8.6 * 10-15 M for
      parathion methyl. The proposed biosensor also exhibited high selectivity,
      reproducibility and stability. The AChE biosensor was also applied in real
      samples for detecting organophosphate pesticides and exhibited acceptable
      recovery. This work demonstrated that the PtPd@NCS had great potential in
      constructing biosensors to detect organophosphate pesticides and other analytes.

PMID- 30218925
TI  - Tracking tonic dopamine levels in vivo using multiple cyclic square wave
      voltammetry.
AB  - For over two decades, fast-scan cyclic voltammetry (FSCV) has served as a
      reliable analytical method for monitoring dopamine release in near real-time in
      vivo. However, contemporary FSCV techniques have been limited to measure  only
      rapid (on the order of seconds, i.e. phasic) changes in dopamine release evoked
      by either electrical stimulation or elicited by presentation of behaviorally
      salient stimuli, and not slower changes in the tonic extracellular levels of
      dopamine (i.e. basal concentrations). This is because FSCV is inherently a
      differential method that requires subtraction of prestimulation tonic levels of
      dopamine to measure phasic changes relative to a zeroed baseline. Here, we
      describe the development and application of a novel voltammetric technique,
      multiple cyclic square wave voltammetry (M-CSWV), for analytical quantification
      of tonic dopamine concentrations in vivo with relatively high temporal resolution
      (10 s). M-CSWV enriches the electrochemical information by generating two
      dimensional voltammograms which enable high sensitivity (limit of detection, 0.17
      nM) and selectivity against ascorbic acid, and 3,4-dihydroxyphenylacetic acid
      (DOPAC), including changes in pH. Using M-CSWV, a tonic dopamine concentration of
      120 +/- 18 nM (n = 7 rats, +/- SEM) was determined in the striatum of urethane
      anethetized rats. Pharmacological treatments to elevate dopamine by selectively
      inhibiting dopamine reuptake and to reduce DOPAC by inhibition of monoamine
      oxidase supported the selective detection of dopamine in vivo. Overall, M-CSWV
      offers a novel voltammetric technique to quantify levels and monitor changes in
      tonic dopamine concentrations in the brain to further our understanding of the
      role of dopamine in normal behavior and neuropsychiatric disorders.

PMID- 30218926
TI  - Periodic polarization of electroactive biofilms increases current density and
      charge carriers concentration while modifying biofilm structure.
AB  - Anodic electroactive biofilms (EABs) need to overcome low current densities for
      applications such as microbial fuel cells or biosensors. EABs can store charge in
      self-produced redox proteins when temporarily left in open circuit, and discharge
      them once the electrode is appropriately repolarized, thus behaving as
      pseudocapacitors. Here we investigated the effect of such periodic polarization
      on the intrinsic nature of the EABs during their entire growth (i.e. starting
      from inoculation and for 10 days) on glassy carbon electrodes. An optimal
      periodic polarization (half-period of 10 s) greatly increased the maximum steady
      state current density delivered by the Geobacter-dominated EABs (up to 1.10 +/-
      0.02 mA cm-2, n = 3 electrodes) when compared to continuously polarized EABs
      (0.41 +/- 0.04 mA cm-2); and increased the amount of electric charges produced
      per hour by 69 +/- 17% even taking into account the half-periods of open circuit.
      This enhancement was highly correlated with a substantial increase in charge
      carriers concentration (10.6 +/- 0.5 mMe- vs. 2.9 +/- 0.6 mMe-), allowing higher
      charge storage capacity and higher electron mobility across the EABs. Our results
      suggest that appropriate periodic polarizations may upregulate the expression of
      heme-containing redox proteins associated with the matrix, such as c-type
      cytochromes. The EABs grown under periodic polarization presented mushroom-like
      structures on their top layers, while EABs grown under continuous polarization
      were flat.

PMID- 30218927
TI  - From electrochemistry to enzyme kinetics of cytochrome P450.
AB  - This review is an attempt to describe advancements in the electrochemistry of
      cytochrome P450 enzymes (EC 1.14.14.1) and to study molecular aspects and
      catalytic behavior of enzymatic electrocatalysis. Electroanalysis of cytochrome
      P450 demonstrates how to translate theoretical laws and equations of classical
      electrochemistry for the calculation of the kinetic parameters of enzymatic
      reactions and then translation of kinetic parameters to interpretation of drug
      drug interactions. The functional significance of cytochrome P450s (CYPs)
      includes the metabolism of drugs, foreign chemicals, and endogenic compounds. The
      pharmaceutical industry needs sensitive and cost-effective systems for screening
      new drugs and investigation of drug-drug interactions. The development of
      different types of CYP-based biosensors is now in great demand. This review also
      highlights the characteristics of electrode processes and electrode properties
      for optimization of the cytochrome P450 electroanalysis. Electrochemical
      cytochrome P450-biosensors are the most studied. In this review, we analyzed
      electrode/cytochrome P450 systems in terms of the mechanisms underlying P450
      catalyzed reactions. Screening of potential substrates or inhibitors of
      cytochromes P450 by means of electrodes were described.

PMID- 30218928
TI  - An integrated automated multispectral imaging technique that simultaneously
      detects and quantitates viral RNA and immune cell protein markers in fixed
      sections from Epstein-Barr virus-related tumours.
AB  - BACKGROUND/AIM: Epstein-Barr virus (EBV) is an oncovirus that is commonly
      associated with the development of lymphomas and epithelial carcinomas. In the
      era of immunotherapy, histological evaluation of EBV-related cancers is currently
      a multi-sample, multi-technique process requiring separate time-consuming
      detection of EBV-encoded small RNAs by in situ hybridisation (ISH), and parallel
      labelling of sections for cancer-associated protein markers. METHODS: Using EBV
      associated tumours as proof-of-concept for feasibility, here we developed an
      approach that allows simultaneous detection of EBV RNAs and multiple protein
      markers such as PD-L1, EBV-LMP, CD8, CD4, CD20, CD30 and CD15on a single tissue
      section based on our recently reported automated staining protocol. RESULTS: We
      successfully combined multiplex immunofluorescence (mIF) to detect 3
      abovementioned protein markers involved in cancer, with ISH, and applied the
      protocol to f tissue samples from patients diagnosed with EBV-associated
      pulmonary lymphoepithelioma-like carcinoma (LELC), gastric carcinoma and
      Hodgkin's Lymphoma. Empowered by the Vectra 3 Automated Quantitative Pathology
      Imaging System, we demonstrate the utility and potential of this integrated
      approach to concurrently detect and quantitate viral RNA and protein biomarkers
      of immune and tumour cells. CONCLUSION: This study represents an important step
      forward in the research and diagnosis of EBV-associated cancers, and could be
      readily modified to include other proteins and RNA markers to apply to other
      malignancies. More importantly, the novel automated ISH-mIF protocol that we
      detailly described here could also be readily reproduced by most of the
      diagnostic and research lab to future projects that aim to look at both RNA and
      protein markers.

PMID- 30218929
TI  - Quantifying N-loss by root abscission: consequences for wheat N budgets and
      delta15N values.
AB  - Lower plant delta15N values relative to source delta15N are commonly attributed
      to 15N efflux. We determined the extent to which root abscission contributes to
      plant N-loss and consequences for plant delta15N. Wheat (Triticum aestivum L. cv.
      SST015) was grown in hydroponics with direct aeration, aeration constrained
      within a pipe and circulation of nutrient solution through sand, representing
      three levels of stability for root growth. The delta15N of nutrient solutions and
      root fragments were periodically determined, as well as root and shoot delta15N.
      Plants in solution had significantly more negative delta15N (-8.9 and -9.20/00)
      than plants in sand (-6.90/00), suggesting greater 15N-loss; root fragments were
      major biomass- (six-fold greater than root dry weight) and N-loss (two-fold
      greater than plant net N uptake) pathways in solution. These plants had more
      ephemeral roots and two-fold more root tips than the sand treatment. We estimated
      that root fragment loss decreased plant delta15N by at least -3.7, -2.6 and 
      1.00/00 in the direct, pipe and sand treatments, respectively. Positive nutrient
      solution delta15N in all treatments relative to the source delta15N suggests that
      plant N, probably derived from efflux, was present in solution. Despite this,
      root abscission and root turnover are also important N-loss pathways in plants,
      while plant delta15N values are probably influenced by a combination of root
      abscission and N efflux.

PMID- 30218930
TI  - Calcium- and hormone-driven regulation of secondary metabolism and cell wall
      enzymes in grape berry cells.
AB  - The efficacy of calcium sprays for improving fleshy fruit resistance to
      abiotic/biotic stress and enhancement of fruit shelf life has increasingly been
      explored. However, because calcium is a powerful secondary messenger in many
      signaling pathways, including those driven by abscisic acid (ABA) and jasmonates,
      it may interfere with the biosynthesis of specialized metabolites highly
      important for fruit and wine quality, such as phenolic compounds. In this study,
      a combination of biochemical and molecular biology approaches were applied to
      grape cell cultures and detached grape berries, in order to investigate the
      effect of calcium in the modulation of enzymes involved in the biosynthesis of
      phenolic compounds and in cell wall organization. Concentrations up to 10 mM
      CaCl2 did not affect cell growth, size or viability, but triggered modifications
      in total phenolics content, particularly in anthocyanin levels in grape cell
      suspensions. The effects of calcium applied alone or in combination with ABA or
      methyl jasmonate (MeJA) were visible in several branches of specialized metabolic
      pathways, confirming that the calcium-hormone interplay regulates the expression
      of phenylalanine ammonia lyase (PAL), stilbene synthase (STS), dihydroflavonol
      reductase (DFR) and UDP-glucose:flavonoid 3-O-glucosyltransferase (UFGT). The
      activity of PAL and UFGT enzymes was also specifically modulated by calcium, ABA
      and MeJA. These results closely correlated to the modifications observed in the
      expression of VvAM1 and VvABCC1 encoding vacuolar anthocyanin transporters.
      Modulation of the expression and activity of pectin methyl esterases (PME) and
      polygalacturonases (PG) by calcium was also evident, confirming an important role
      of calcium in cell wall organization via the regulation of enzyme activity,
      besides its well-known role in the formation of cross links between pectin
      molecules. Overall, this study uncovers important biochemical mechanisms induced
      by calcium and stress hormones on grape berries, and highlights the need to
      consider the consequences of calcium treatments and stress for fruit quality.

PMID- 30218931
TI  - Simultaneous nitrification-denitrification and membrane fouling alleviation in a
      submerged biofilm membrane bioreactor with coupling of sponge and biodegradable
      PBS carrier.
AB  - Simultaneous nitrification-denitrification (SND) was achieved in submerged
      biofilm membrane bioreactor (SBF-MBR) treating low carbon/nitrogen (C/N) ratio
      wastewater. A novel bio-carrier coupling of sponge and biodegradable
      poly(butanediol succinate) (PBS) was applied as external carbon source and
      biofilm carrier. Result represented that NH4+-N and total nitrogen removal
      efficiencies were high of 99.1% and 94.3% in the SBF-MBR. Protein (PN) contents
      from SND-biofilm were reduced by 10.5% and 44.3% in TB-EPS and LB-EPS, while
      polysaccharides (PS) were reduced by 45.8% and 34.8%, respectively. 3D-EEM
      spectra indicated that protein-like, humic acid-like and fulvic acid-like
      substances were the main components in EPS and their peak intensities were
      reduced. Additionally, membrane fouling of SBF-MBR was improved after the
      achievement of biofilm. Microbial community analysis showed that Simplicispira,
      Thauera, Desulfovibrio, Dechlorobacter and Acinetobacter were dominant genus,
      which indicated co-existence of nitrifying bacteria, heterotrophic denitrifiers
      and aerobic denitrifiers in the SBF-MBR.

PMID- 30218932
TI  - Preparation of the recycled and regenerated mesocarbon microbeads-based solid
      acid and its catalytic behaviors for hydrolysis of cellulose.
AB  - Mesocarbon microbeads (MCMB) from coal tar pitch have excellent mechanical
      strength, high density, and good thermal stability. Moreover, a great deal of
      aromatic constituents occur on its surface, favoring the substitution reaction of
      sulfonic group. Results showed that the total acid and -SO3H amount was 4.36
      mmol/g and 2.18 mmol/g, respectively. Moreover, the yield of total reducing sugar
      (TRS) and conversion ratio (Cr) for pretreated cellulose (DP = 101.5) can reach
      66.7% and 68.8% at 140  degrees C for 240 min in distilled water, respectively.
      After four recycles, the TRS and Cr decreased by 12.6% and 10.2%, respectively.
      Through the secondary and third regeneration for the catalyst, acid density still
      reached 88.1% and 87.2% of the initial R1-MCMB-SO3H, demonstrating excellent
      regeneration ability and recyclability of the solid acid. Therefore, MCMB-based
      solid acid exhibits an attractive potential in the conversion of cellulose into
      platform chemical compounds.

PMID- 30218933
TI  - Enhanced anaerobic digestion of ammonia-rich swine manure by zero-valent iron:
      With special focus on the enhancement effect on hydrogenotrophic methanogenesis
      activity.
AB  - Zero-valent iron (ZVI) supplementation for improving anaerobic digestion (AD) of
      ammonia-rich swine manure (initial ammonia-N ~5000 mg/L) was tested. The addition
      of 5 g/L ZVI powder apparently accelerated the acidification process to produce
      more volatile fatty acids (VFAs) and optimized the fermentation type by
      contributing to a lower system oxidation-reduction potential (ORP) level of 
      181.7 to -250.0 mV favorable for ethanol-type and butyric-type fermentation
      during day 14-30, in comparison with that of -164.3 to -216.3 mV in the control
      group favorable for propionic-type. Overall, ZVI significantly decreased the
      proportion of propionic acid from 49.8% to 30.9% while increased the proportion
      of n-butyric acid from 6.8% to 18.7%. Microbial analysis revealed that fast
      growing and ammonia-tolerant hydrogenotrophic Methanoculleus species were
      enriched with ZVI, helping achieve a 54.2% higher CH4 yield relative to control.
      Results from this study demonstrated the potential of ZVI addition to enhance AD
      of ammonia-rich animal manure.

PMID- 30218934
TI  - Shifting product spectrum by pH adjustment during long-term continuous anaerobic
      fermentation of food waste.
AB  - Anaerobic fermentation is widely used to recover different products from food
      waste, and in this study, the evolution of fermentation products and microbial
      community along with pH variation was investigated thoroughly using four long
      term reactors. Lactic fermentation dominated the system at pH 3.2-4.5 with lactic
      acid concentration of 5.7-13.5 g/L, and Lactobacillus was the superior sort.
      Bifidobacteria increased significantly at pH 4.5, resulting in the increase of
      acetic acid. Butyric acid fermentation was observed at pH 4.7-5.0.
      Bifidobacterium, Lactobacillus, and Olsenella were still dominant, but the lactic
      acid produced by them was converted to volatile fatty acids (VFAs) rapidly by
      Megasphaera, Caproiciproducens, Solobacteria, etc. Mixed acid fermentation
      occurred at pH 6.0 with the highest concentration 14.2 g/L of VFAs, and the
      dominant Prevotella and Megasphaera converted substrates to VFAs directly. On the
      whole, pH 4.5 and 4.7 led to the highest hydrolysis rate of 50% and acidification
      rate of 45%.

PMID- 30218935
TI  - Pyrolysis behavior and economics analysis of the biomass pyrolytic polygeneration
      of forest farming waste.
AB  - The pyrolysis behavior of Chinese chestnut and Jatropha curcas shells (CNS and
      JCS, respectively) were investigated to determine the optimum operating
      temperature for biomass pyrolytic polygeneration systems. At low temperatures
      (250-450  degrees C), CO2 was the main component of the pyrolytic gas, and high
      acidity oil was obtained. When the temperature increased to 550-650  degrees C,
      phenol-enriched oil and high LHV biochar (~26 MJ/kg) were obtained; H2 and CO
      yields increased. At high temperatures (750-950  degrees C), heavy-oil and high
      LHV pyrolytic gas (~15 MJ/m3) were obtained. Meanwhile, the biochar showed a
      highly condensed aromatic ring system and low H/C (~0.1) and O/C (~0.05) ratios.
      CNS and JCS biochars showed different tendencies with regard to their structure
      evolution. An economic analysis was performed, which suggested that the optimum
      operating temperatures were 450  degrees C for CNS and 350  degrees C for JCS.

PMID- 30218936
TI  - Biotransformation of flower waste composting: Optimization of waste combinations
      using response surface methodology.
AB  - Flower waste (FW) is disposed off in the rivers or mixed with solid waste for
      landfilling that pollutes the environment and causes harmful effects on human
      health and aquatic life. It is rich in nutrient content and easily converted into
      the compost. Therefore, the objective of the present research was to optimize the
      combinations of flower waste and cow dung during agitated pile composting using
      response surface methodology. Thirteen different agitated piles were used for
      composting using the central composite design. The optimum combination from
      central composite design was 65 kg floral waste, 25 kg cattle dung and 10 kg
      sawdust having 7.10 pH, 3.31 mS cm-1 electrical conductivity, 32.98% total
      organic carbon and 14 Carbon to Nitrogen ratio during the end phase of the
      composting period. The nutrient concentrations into the final compost were within
      the acceptable limit and also found to be beneficial for the growth of plants.

PMID- 30218937
TI  - Acetone/water oxidation of corn stover for the production of bioethanol and
      prebiotic oligosaccharides.
AB  - Ethanol production at high-gravity promise to achieve concentrations over the
      threshold for an economical distillation process and concurrently reduce water
      consumption. However, a persisting limitation is the poor mass transfer
      conditions resulting in low ethanol yields and concentrations. Hereby, the
      combination of an acetone/water oxidation pretreatment process (AWO) with a
      liquefaction/saccharification step, using a free-fall mixer, before simultaneous
      saccharification and fermentation (SSF) can realize ethanol concentrations of up
      to ca. 74 g/L at a solids content of 20 wt%. The free-fall mixer achieved a
      biomass slurry viscosity reduction by 87% after only 2 h of enzymatic
      saccharification, indicating the efficiency of the mixing system. Furthermore,
      the direct enzymatic treatment of AWO pretreated corn stover (CS) by a GH11
      recombinant xylanase, led to the production of xylooligosaccharides (XOS) with
      prebiotic potential and the removal of insoluble fibers of hemicellulose improved
      the glucose release of AWOCS by 22%.

PMID- 30218938
TI  - Conversion of poplar into bio-oil via subcritical hydrothermal liquefaction:
      Structure and antioxidant capacity.
AB  - Subcritical hydrothermal liquefaction of poplar was performed at 220-280  degrees
      C, and the liquid phase produced was extracted by ethyl acetate to obtain light
      oil (LO), which contained LO1 (water-soluble) and LO2 (ethyl acetate-soluble).
      The residue was further extracted with acetone to produce heavy oil (HO) and
      solid residue (SR). The highest bio-oil yield of 19.88% was obtained at 260 
      degrees C. The HO produced at 260  degrees C had the highest content of C
      (69.13%) and the higher heating value was 27.97 MJ/kg. The O/C and H/C ratios of
      LO were higher than those of HO due to less aromatics in LO. Oxidative inhibition
      rates of bio-oils, measured in DPPH-ethanol solution at a concentration of 0.1
      mg/mL, reached 60.76% for LO1 while 90.29% and 90.85% for LO2 and HO,
      respectively. The bio-oil with good antioxidant activity can be utilized as an
      additive in bio-diesel to improve oxidation stability.

PMID- 30218939
TI  - Fecal microbiota transfer for bowel disorders: efficacy or hype?
AB  - PURPOSE OF REVIEW: Dysbiosis has been related to the pathophysiology of disorders
      of - gut-brain interaction (DGBI) including irritable bowel syndrome (IBS) and
      functional constipation (FC). Accordingly, modulation of gut microbiota has been
      proposed as a potential treatment for these disorders. Gut microbiota modulation
      can be effected by probiotics, prebiotics, symbiotics, postbiotics, antibiotics
      and fecal transplantation (FMT) or bacteriotherapy. The latter is currently used
      for recurrent or severe Clostridium difficile colitis and has been the focus of
      recent research in IBS and FC. RECENT FINDINGS: Several case series reported
      promising results for FMT in patients with IBS and FC, which prompted the
      conduction of randomized controlled trials (RCT) in these DGBI. SUMMARY: Both
      case series and RCTs are herein discussed. To the best of our knowledge, as of
      yet, 5 RCTs have been published on IBS and one in FC with slow colonic transit.
      In IBS, the majority of studies have used the IBS severity scoring system (IBS
      SSS) as an outcome measure; however, the selection criteria were different among
      the trials as well as the route and form of administration of the FMT. Therefore,
      the results are inconsistent and no conclusion can be drawn. Some studies suggest
      that the presence of post-infection (PI)-IBS and the baseline microbiota status
      in the donors could be predictor factors of successful FMT in IBS. In
      constipation with slow colonic transit, the FMT seems to be more effective,
      although the data is based on only one RCT. We believe that larger RCTs,
      controlled with true placebos and considering baseline intestinal microbiota of
      the study subjects as well as donors' microbiota are still needed before
      recommending FMT in IBS and/or FC. History of previous GI infection (e.g. PI-IBS)
      and IBS subtypes should also be taken into account.

PMID- 30218940
TI  - Endocannabinoids in the treatment of gasytrointestinal inflammation and symptoms.
AB  - The evolving policies regarding the use of therapeutic Cannabis have steadily
      increased the public interest in its use as a complementary and alternative
      medicine in several disorders, including inflammatory bowel disease.
      Endocannabinoids represent both an appealing therapeutic strategy and a
      captivating scientific dilemma. Results from clinical trials have to be carefully
      interpreted owing to possible reporting-biases related to cannabinoids
      psychotropic effects. Moreover, discriminating between symptomatic improvement
      and the real gain on the underlying inflammatory process is often challenging.
      This review summarizes the advances and latest discovery in this ever-changing
      field of investigation, highlighting the main limitations in the current use of
      these drugs in clinical practice and the possible future perspectives to overcome
      these flaws.

PMID- 30218941
TI  - Sociodemographic, neighborhood, psychosocial, and substance use correlates of
      cocaine use among Black adults: Findings from a pooled analysis of national data.
AB  - OBJECTIVE: Cocaine use (CU) is serious a public health issue affecting U.S.
      adults, including Blacks. Cocaine-related overdose deaths have also trended
      upwards among this population. However, there remains a lack of research on
      correlates of CU among a nationally representative sample of Black adults.
      METHODS: The current study examines the prevalence and correlates of past-year CU
      among Black adults aged 18 and older (N = 9,821). Data from the National Survey
      on Drug Use and Health (2015-2016) were used and a weighted logistic regression
      model was estimated. RESULTS: Findings showed 2.4% of Black adults reported past
      year CU-significantly higher than rates of CU among other assessed racial groups.
      Opioid use/misuse, encounters with drug dealers, easier access to cocaine,
      unemployment, and being 35 or older were associated with increased odds of CU.
      Greater risk perception of CU and religiosity were associated decreased odds of
      CU. CONCLUSION: Results identified several correlates associated with past-year
      CU among Black adults. Findings suggest addressing CU among this population will
      likely require the development of multilevel prevention and intervention
      strategies and an increased focus on opioid use/misuse as opioids have been
      recently implicated in cocaine-related overdose deaths.

PMID- 30218942
TI  - Failure to generate baseline muscle motor evoked potentials during spine surgery:
      Risk factors and association with the postoperative outcomes.
AB  - OBJECTIVE: To identify factors associated with the failure to generate baseline
      muscle motor evoked potentials (mMEPs) during spinal surgery, and to determine
      the association between baseline mMEP generation and postoperative outcomes.
      METHODS: A total of 345 patients who underwent spine surgery with intraoperative
      mMEP monitoring were included, and we retrospectively reviewed their
      demographic/clinical parameters, and mMEP recording results according to lesion
      locations. RESULTS: Multivariable logistic regression analysis revealed that
      preoperative Medical Research Council grade of the weakest muscle <3 was
      significantly associated with failure of baseline mMEP generation in both
      cervical and thoracic lesions. In addition, high intramedullary T2 signal
      intensity on spine MRI for cervical lesions and male sex for thoracic lesions
      were also significantly associated with baseline mMEP generation failure.
      Moreover, the failure of baseline mMEP generation was a significantly associated
      factor for poor functional outcome in patients with thoracic lesions. CONCLUSION:
      Sex, radiological abnormality, and preoperative functional status were associated
      with baseline mMEP generation failure during spine surgery with different
      patterns according to lesion location. Moreover, baseline mMEP generation failure
      in thoracic lesion could be associated with risk of postoperative deficits.
      SIGNIFICANCE: The risk of baseline mMEP recording failure could be evaluated
      based on preoperative clinical parameters.

PMID- 30218943
TI  - The role of disgust in body image disturbance: Incremental predictive power of
      self-disgust.
AB  - The relationship between disgust and symptoms of disorders characterized by body
      image disturbance (BID) is increasingly being examined. In cognitive-behavioral
      models of psychopathology, disgust may function as a negative emotional response
      to perceived body defects, leading to avoidance and compulsive behavior. Little
      research has examined the role of self-disgust - a form of disgust that may be
      particularly relevant to the body. The present study is a descriptive analysis of
      the association between BID and self-disgust, controlling for other related
      variables. Two non-clinical samples completed measures of BID, self-disgust,
      negative affect, anxiety sensitivity, disgust propensity, and disgust
      sensitivity. Although BID was associated with all three forms of disgust at the
      bivariate level, in multivariate analyses self-disgust emerged as a unique
      predictor of BID, above and beyond all included variables, although effect sizes
      were small. Potential implications for understanding, preventing, and treating
      body image-related disorders are discussed.

PMID- 30218944
TI  - Artificial hand illusions dynamics: Onset and fading of static rubber and virtual
      moving hand illusions.
AB  - The aim of this study was to investigate the temporal dynamics of two
      multisensory body illusions: a static rubber hand illusion (RHI) and a moving
      virtual hand illusion (VHI). We explored the onset and fading of these illusions.
      A sense of ownership questionnaire and proprioceptive drift were used for
      illusion estimation. Novel kinematic analysis was applied for the VHI. Positive
      dynamics of ownership were found in the RHI but not in the VHI. The general
      dynamics of proprioceptive drift were similar in both illusions: during the onset
      phase of artificial hand representation proprioceptive drift gradually increased,
      and during the fading phase - it gradually decreased. Kinematic analysis of the
      VHI revealed several motion features (such as jerk, smoothness, velocity),
      predicted illusion measures, and probably reflected that participants with higher
      motor abilities and better adaptation to new sensory conditions may have better
      multisensory integration mechanisms that are responsible for the ownership
      illusion.

PMID- 30218945
TI  - Conscious awareness of self-relevant information is necessary for an incidental
      self-memory advantage.
AB  - Co-presenting an item with self-relevant vs. other-relevant information under a
      non-self-referential encoding context can produce a memory advantage. The present
      study examined the relative contributions of conscious vs. unconscious processing
      of self-cues to this incidental self-memory advantage. During encoding, the
      participant's own or another person's name was presented supraliminally or
      subliminally prior to the presentation of each target word. Consistent across two
      experiments, we found better memory for words preceded by the own name vs.
      another name but only when the names were presented supraliminally. The masked
      priming effect produced by the own name in Experiment 2 suggests that the absence
      of a self-memory advantage following subliminal name presentation was unlikely
      due to subliminal self-processing being too weak. Our findings suggest that
      conscious awareness of self-cues is necessary for an incidental self-memory
      advantage. Potential qualitative differences between conscious vs. unconscious
      self-processing mediating the impact of self on memory are discussed.

PMID- 30218946
TI  - A process of developing a national practice assessment document.
AB  - This paper will share how one country within the United Kingdom (UK) collaborated
      on a national partnership approach in developing a consistent pre-registration
      undergraduate nursing practice learning assessment document. In 2011 the Scottish
      Heads of Academic Nursing and Allied Health Professionals (SHANAHP, now Council
      of Deans Scotland, CoDS) agreed to support the development of a Scottish national
      approach to practice learning assessment document (the "Scottish Ongoing
      Achievement Record"). Whilst no direct funding was received to support this work,
      each HEI agreed that this work would be recognised via the release of staff time
      to enable completion. Utilising a communities of practice approach to
      collaborative working, the national group incorporated the collective knowledge
      and experience of representatives from all Higher Education Institutes (HEIs) in
      Scotland that provided undergraduate pre-registration nurse education. The work
      of the group will be described in four phases, Mapping of Influential Drivers;
      Guiding Principles and Good Practice; Document development; and Implementation.
      Appraisal of the advantages of this approach in light of international literature
      will be considered alongside challenges encountered during development and
      implementation.

PMID- 30218947
TI  - Benefits and challenges of a nursing service-learning partnership with a
      community of internally-displaced persons in Colombia.
AB  - Service-learning partnerships between nursing programs and health care settings
      in vulnerable communities may be challenging to initiate, but can offer multiple
      benefits for students, faculty, and the community served. The aim of this
      qualitative descriptive study was to explore the benefits and challenges of
      establishing a service-learning partnership between a university nursing program
      and an isolated community of internally-displaced persons in Medellin, Colombia.
      Semi-structured, in-depth interviews were conducted with 10 nursing professors
      and nine students who participated in the service-learning partnership.
      Interviews were audio-recorded, transcribed and analyzed using qualitative
      content analysis. Main benefits identified were: learning about the social
      determinants of health, development of compassion, appreciation for the community
      nursing role, professional growth and development, community engagement and
      increased access to care for community members. Challenges related to the service
      learning experience included feelings of moral distress, lack of value for
      community nursing, and conflict with traditional biomedical approaches to care.
      Several threats to program sustainability were also identified. Professors and
      students offered several recommendations for program improvement, including
      interdisciplinary collaboration, documentation and dissemination of the service
      learning experience, increased community autonomy and capacity for self-care, and
      curricular changes to enhance recognition of the importance of community nursing.

PMID- 30218948
TI  - Distribution patterns for metabolites in medicinal parts of wild and cultivated
      licorice.
AB  - Licorice is a famous Chinese medicinal material widely applied worldwide in food
      and drugs. It possesses a substantial share in the international and domestic
      markets. While the demand is continuously increasing, wild-type of licorice is
      gradually disappearing. Its cultivated-type is significantly different compared
      to its wild-type, especially the bioactive compounds in dried roots and rhizomes
      (the medicinal parts of wild and cultivated licorice) are responsible for their
      quality difference. In this study, a total of thirty-two constituents, including
      seventeen secondary compounds and fifteen primary metabolites, were
      simultaneously analyzed by UFLC coupled with triple quadrupole-linear ion trap
      mass spectrometry (UFLC-QTRAP-MS/MS) in different medicinal parts of licorice.
      Our findings indicated that the content of major bioactive compounds in wild
      licorice were significantly higher than those in its cultivated-type. The
      metabolites in rhizomes showed totally different outcomes between wild and
      cultivated licorice. Remarkably high level of some important amino acids related
      to abiotic stress (drought and salt) were found in wild licorice. Notably, the
      high contents of phenylalanine and compounds in upstream of flavonoid synthesis
      in cultivated licorice suggested that the synthesis may differ at the initial
      stage. The distribution pattern of metabolites in different medicinal parts of
      wild and cultivated licorice will not only provide a novel clue in agricultural
      breeding but also facilitate the further study on their quality formation.

PMID- 30218949
TI  - Recovery of polyphenols onto porous carbons developed from exhausted grape
      pomace: A sustainable approach for the treatment of wine wastewaters.
AB  - Removal of total polyphenols (TPP) is not only necessary as a pretreatment
      stepfor anaerobic digestion of wine wastewaters (WWW) but also the recovered
      polyphenols can be used as a dietary supplement. With a view to make the process
      sustainable, eco-efficient and cost effective, exhausted grape pomace (EGP) after
      the extraction of polyphenols was impregnated with ZnCl2 (1:1.5) and further
      activated at 450  degrees C for 1 h under inert atmosphere. The GPAC (grape
      pomace activated carbon) thus developed exhibited well-developed porosity with a
      predominance of micropores, high surface area and selective surface binding
      sites. Batch adsorption conducted on diluted WWW revealed the better performance
      of GPAC (84.3% removal) as compared to EGP (48.5% removal) under similar
      conditions; with maximum adsorption taking place at pH 3.8. While pH studies
      indicated a possible electron-donor-acceptor mechanism in the binding of TPP,
      kinetic studies indicated that diffusion was mediated by the porosity in GPAC.
      Isotherm studies conducted on GPAC and commercial carbon (CAC) revealed
      multilayer binding under WWW while Langmuir model was operative under simulated
      conditions. Contrary to the better performance of CAC, the same for GPAC was
      comparable at higher dosage where >80%TPP was removed from undiluted WWW. The
      phenol adsorption capacity of GPAC from real (28.4 mg/g) and from simulated
      wastewater (142.6 mg/g) was higher as compared to other reported adsorbents.
      Desorption of TPP from loaded GPAC was maximum (~91%) with 1:1 ethanol-water
      solvent. The results reveal a sustainable eco-friendly solution for valorisation
      of exhausted grape pomace for recovery of polyphenols from wine wastewater.

PMID- 30218950
TI  - First large-scale ecological impact study of desalination outfall reveals trade
      offs in effects of hypersalinity and hydrodynamics.
AB  - Desalination is an increasingly common method of meeting potable water demands,
      but the associated ecological risks are not well understood. Seawater
      desalination plants discharge large volumes of hypersaline brine directly into
      the ocean, raising concerns about potential impacts to marine life. In order to
      reduce impacts of brine, newer desalination outfalls are often fitted with high
      pressure diffusers that discharge brine at high velocity into the water column,
      increasing the mixing and dilution of brine with ocean water. However, there are
      few published studies of marine impacts of desalination brine, and no well
      replicated before-after designs. Here we report a six-year study testing for
      impacts and subsequent recovery of sessile marine invertebrate recruitment near a
      desalination outfall with high-pressure diffusers. We used a Multiple Before
      After-Control-Impact (MBACI) design to test for impacts and recovery at two
      distances (30 m and 100 m) from a 250 ML/day plant outfall, as well as a gradient
      design to test the strength of impacts relative to distance from the outfall. The
      diffusers achieved the target of less than 1 psMU salinity difference to
      surrounding ambient waters within 100 m of the discharge outfall, but sessile
      invertebrates were nonetheless impacted. Polychaetes, bryozoans and sponges
      reduced in cover as far as 100 m from the outfall, while barnacles showed the
      opposite pattern and were more abundant near the discharging outfall. Ecological
      impacts were disproportionate to the relatively minor change in salinity (~1
      psMU), suggesting a mechanism other than salinity. We propose that impacts were
      primarily driven by changes in hydrodynamics caused by the diffusers, such as
      higher near-bed flow away from the outfall. This is consistent with flow
      preferences of various taxonomic groups, which differ due to differences in
      settlement and feeding abilities. High-pressure diffusers designed to reduce
      impacts of hypersalinity may inadvertently cause impacts through hydrodynamics,
      leading to a trade-off in minimizing combined salinity and hydrodynamic stress.
      This study provides the first before-after test of ecological impacts of
      desalination brine on sessile marine communities, and rare insight into
      mechanisms behind impacts of a growing form of human disturbance.

PMID- 30218951
TI  - Opportunities for plant natural products in infection control.
AB  - The continued spread of antimicrobial resistance represents one of the most
      serious infectious disease threats to global health. There is consensus that a
      key component of addressing this threat is to replenish the waning pipeline of
      antimicrobials, with attention being paid to novel mechanisms of action. This
      includes the development of new classes of classic bacteriostatic and
      bactericidal antibiotics as well as antivirulence drugs, and it is especially in
      these areas where plant natural products demonstrate great potential. To this
      end, we discuss the unique characteristics of plant natural products, the
      advantages of plants as a resource for anti-infective drug discovery, and recent
      technologies that have further enabled this path of inquiry. As a result of
      emerging realization of their advantages, plant natural products have recently
      enjoyed increased scrutiny in antimicrobial lead discovery, and they will
      continue to serve as a source of leads. We conclude that plant natural products
      represent a promising and largely untapped source of new chemical entities from
      which novel anti-infectives can be discovered.

PMID- 30218952
TI  - Polydatin ameliorates dextran sulfate sodium-induced colitis by decreasing
      oxidative stress and apoptosis partially via Sonic hedgehog signaling pathway.
AB  - BACKGROUND: Inflammation, oxidative stress and epithelial barrier dysfunction
      have been implicated in inflammatory bowel disease (IBD) pathology. The targeted
      inhibition of these features may represent a promising therapeutic strategy for
      IBD. Polydatin is an effective natural antioxidant that possesses strong
      antioxidant and anti-apoptotic properties. Thus, we studied the protective
      effects of polydatin treatments on a mouse model of experimental colitis.
      METHODS: Acute colitis was experimentally induced by adding 3% dextran sulfate
      sodium (DSS) to the drinking water provided to mice for 7 days and by
      administering different doses of polydatin (15, 30, or 45 mg/kg) during the same
      period. Mice were also treated with the Sonic hedgehog (Shh) pathway inhibitor
      cyclopamine to estimate the efficacy of polydatin and Shh inhibitors on colitis.
      The disease activity index (DAI), colon length, histology, levels of oxidative
      and apoptotic mediators and levels of Shh pathway components were evaluated.
      RESULTS: The polydatin treatment significantly attenuated the DAI, colon
      shortening and histological damage. In addition, polydatin administration
      effectively decreased malondialdehyde (MDA) levels and increased the activities
      of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase
      (GSH-Px). Polydatin also inhibited apoptosis in mice with colitis by
      downregulating the expression of the pro-apoptotic proteins Bax, caspase 3 and
      cleaved caspase 3 and increasing the expression of the anti-apoptotic protein Bcl
      2. Furthermore, polydatin modulated Shh signaling pathway activation. After
      polydatin treatment, the main components of the Shh pathway, including Shh,
      Patched (Ptc), Smoothened (Smo), and glioblastoma-1 (Gli1), were upregulated at
      the mRNA and protein levels. Blockade of the Shh pathway using cyclopamine
      abolished the effects of polydatin on mice with colitis. CONCLUSION: Based on
      these observations, polydatin may suppress experimental colitis at least
      partially by regulating the Shh signaling pathway.

PMID- 30218954
TI  - Polymorphisms in the angiotensin I converting enzyme (ACE) gene are associated
      with multiple sclerosis risk and response to Interferon-beta treatment.
AB  - BACKGROUND: Multiple sclerosis (MS) as a chronic autoimmune demyelinating
      disorder of the central nervous system has been associated with numerous genetic
      and environmental factors among them are functional variants within the
      angiotensin I converting enzyme (ACE) gene. METHODS: In the present study, we
      genotyped the rs4359 (C/T) and rs1799752 (Insertion (I)/Deletion (D)) of this
      gene in 391 MS patients and 380 age- and sex-matched controls. RESULTS: We found
      significant overrepresentation of the I allele of the rs1799752 in MS patients
      compared with healthy subjects (Adjusted P value = 0.03, OR (95% CI) = 1.28 (1.05
      1.57). The same allele was associated with MS risk in co-dominant and dominant
      models (Adjusted P values of 0.007 and 0.002 respectively). The allele and
      genotype frequencies of the rs4359 were not significantly different between cases
      and controls. Moreover, the I allele of the rs1799752 was significantly
      overrepresented in MS patients who were irresponsive to IFN-beta compared with
      healthy subjects (Adjusted P value = 0.04, OR (95% CI) = 1.57 (1.08-2.29)). The
      same allele was associated with irresponsiveness to IFN-beta in dominant model
      (Adjusted P value = 0.02, OR (95% CI) = 2.32 (1.22-4.42)). CONCLUSION: The
      present study provides further evidences for the role of ACE in MS risk or
      response of patients to IFN-beta treatment.

PMID- 30218953
TI  - Brusatol ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental
      colitis in rats: Involvement of NF-kappaB pathway and NLRP3 inflammasome.
AB  - Brusatol is a main bioactive component derived from the Chinese medicinal plant
      Brucea javanica, which is traditionally used for the treatment of dysentery (also
      known as ulcerative colitis, UC). Previously, we have designed a novel brusatol
      self-microemulsifying drug delivery system (BR-SMEDDS) to increase its solubility
      and bioavailability, and enhance its bioactivities. In the present study, we
      established 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model
      in vivo and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro, to
      investigate the potential anti-inflammatory effect and underlying mechanism of BR
      SMEDDS. Disease activity index (DAI) including body weight, stool consistency and
      gross bleeding was measured. Macroscopic and histological evaluations of colons
      were conducted. Relevant molecular events were determined by ELISA, qRT-PCR,
      immunohistochemistry or Western blotting. The results showed that BR notably
      inhibited the productions of TNF-alpha, pro-IL-1beta, PGE2 and NO, and suppressed
      the NF-kappaB signaling pathway in LPS-stimulated macrophages. In parallel with
      the vitro experimental results, BR significantly attenuated diarrhea, colonic
      shortening, macroscopic damage and histological injury. BR treatment also
      increased the levels of TGF-beta and IL-4, decreased the contents of IL-1beta and
      IL-18, and elevated the levels of CAT, GSH and SOD in the colons. Furthermore, BR
      also markedly activated the Nrf2 expression and suppressed the NLRP3 inflammasome
      activation. Taken together, the anti-UC effect of BR might be intimately
      associated with the suppression of NF-kappaB and NLRP3-mediated inflammatory
      responses, and regulation of Nrf2-mediated oxidative stress. BR might have the
      potential to be further developed into a promising therapeutic agent for colitis
      treatment.

PMID- 30218955
TI  - Inhibitory effect of Chrysanthemum morifolium flower extract on the formation of
      heterocyclic amines in goat meat patties cooked by various cooking methods and
      temperatures.
AB  - The effect of Chrysanthemum morifolium flower extract (CME) was investigated on
      the formation of heterocyclic amines (HCAs) in goat meat patties cooked at
      different temperatures by different cooking methods. In patties without CME, the
      level of total HCAs increased analogously with the increase in cooking
      temperature. The inhibitory effect of CME on HCAs ranged from 14% to 82%. The
      total HCAs content were reduced by 46%, 40% and 35% in pan fried, deep fat fried
      and oven roasted goat meat patties, respectively, at 175  degrees C. While, at
      225  degrees C, the amount of total HCAs was decreased by 52%, 47% and 32% in
      deep fat fried, pan fried and oven roasted patties respectively, whereas, in
      barbecue patties the reduction was 36%. Hence, it is concluded that the effect of
      CME was more prominent in deep fat frying and pan frying cooking methods and
      increase in temperature enhance the efficacy of CME in both cooking methods.

PMID- 30218956
TI  - Effects of Portulaca oleracea L. extract on lipid oxidation and color of pork
      meat during refrigerated storage.
AB  - The study explored the preservation effect of Portulaca oleracea L. extract (POE)
      on pork meat under refrigerated conditions for 9 days. POE was tested for
      antioxidant activity and antibacterial activity in vitro and the results showed
      that POE has strong antioxidant activity and has antibacterial activity against
      Pseudomonas aeruginosa, Bacillus subtilis and Bacillus cereus to some extent.
      Effect of POE in different levels (0.25%, 0.50% and 1.0%) on quality and
      shelflife of pork meat storage were evaluated. Results showed that the treatments
      of POE significantly inhibited microbial growth,delayed lipids oxidation, reduced
      values of thiobarbituric acid reactive substances (TBARS) and total volatile base
      nitrogen (TVB-N), increased superoxide dismutase (SOD) and glutathione peroxidase
      (GSH-Px) activities and in a dose-dependent manner (P < .05). Concomitantly,
      1.0%POE and 0.50%POE treatments had better appearance compared with control after
      9 days storage. All results confirmed that POE could effectively maintain the
      quality of chilled pork compared to control.

PMID- 30218957
TI  - Structure and biosynthesis of benzoxazinoids: Plant defence metabolites with
      potential as antimicrobial scaffolds.
AB  - Benzoxazinoids, comprising the classes of benzoxazinones and benzoxazolinones,
      are a set of specialised metabolites produced by the plant family Poaceae
      (formerly Gramineae), and some dicots. The family Poaceae in particular contains
      several important crops like maize and wheat. Benzoxazinoids play a role in
      allelopathy and as defence compounds against (micro)biological threats. The
      effectivity of benzoxazinones in these functionalities is largely imposed by the
      subclasses (determined by N substituent). In this review, we provide an overview
      of all currently known natural benzoxazinoids and a summary of the current state
      of knowledge of their biosynthesis. We also evaluated their antimicrobial
      activity based on minimum inhibitory concentration (MIC) values reported in
      literature. Monomeric natural benzoxazinoids seem to lack potency as
      antimicrobial agents. The 1,4-benzoxazin-3-one backbone, however, has been shown
      to be a potential scaffold for designing new antimicrobial compounds. This has
      been demonstrated by a number of studies that report potent activity of synthetic
      derivatives of 1,4-benzoxazin-3-one, which possess MIC values down to 6.25 MUg mL
      1 against pathogenic fungi (e.g. C. albicans) and 16 MUg mL-1 against bacteria
      (e.g. S. aureus and E. coli). Observations on the structural requirements for
      allelopathy, insecticidal, and antimicrobial activity suggest that they are not
      necessarily conferred by similar mechanisms.

PMID- 30218958
TI  - Tolerability and effectiveness of 4-factor prothrombin complex concentrate (4F
      PCC) for warfarin and non-warfarin reversals.
AB  - PURPOSE: Current guidelines favor 4F-PCC over plasma for warfarin reversal.
      Uncertainty remains on its thrombotic risk and hemostatic effectiveness when used
      for direct-acting oral anticoagulants (DOACs), transplants, massive transfusion
      protocols (MTP), and non-anticoagulated patients. This study sought to evaluate
      the tolerability and effectiveness of 4F-PCC in a real-world setting. MATERIALS
      AND METHODS: This was a retrospective study of adults who received 4F-PCC from
      March 2014 to December 2015. The primary outcome was thromboembolic events within
      14 days. The secondary outcome was hemostatic effectiveness within 24 h. RESULTS:
      The final analysis included 212 patients. Primary reversal indication was major
      bleed in 165 patients (77.8%) and emergent surgery in 47 patients (22.2%).
      Thromboembolism occurred in 22 patients (10.4%), more in emergent surgery than
      major bleed reversals (17% and 8.5%, respectively). MTP and heart transplant
      patients had the highest thromboembolic event rates (44.4% and 28.6%,
      respectively). Hemostatic effectiveness was 65.8% (68% in major bleed and 58.1%
      in emergent surgery). DOAC patients achieved hemostasis most often (78.9%).
      Administration of any reversal agent, major surgery within 14 days, and MTP
      activation were significant predictors of thromboembolism. CONCLUSIONS: Use of 4F
      PCC in this real-world setting was associated with variable thromboembolic and
      hemostatic effectiveness rates based on the indication for reversal.

PMID- 30218959
TI  - Antibiotics has more impact on mortality than other early goal-directed therapy
      components in patients with sepsis: An instrumental variable analysis.
AB  - PURPOSE: To estimate the effect of each of the EGDT components, as well as of the
      antibiotics, on length-of-stay and mortality. METHODS: Prospective cohort in
      three hospitals. Adult patients admitted by the Emergency Rooms (ER) with
      infection and any of systolic blood pressure < 90 mmHg or lactate >4 mmol/L. An
      instrumental analysis with hospital of admission as the instrumental variable was
      performed to estimate the effect of each intervention on hospital mortality and
      secondary outcomes. RESULTS: Among 2587 patients evaluated 884 met inclusion
      criteria, with a hospital mortality rate of 17% (n = 150). In the instrumental
      analysis, the only intervention associated with an absolute reduction in
      mortality (21%) was the use of antibiotics in the first 3 h. In patients with
      lactate values >=4 mmol/L in the ER, a non-decrease of at least 10% at six hours
      was independently associated with mortality (OR = 3.1; 95%CI = 1.5-6.2).
      CONCLUSIONS: Among patients entering ER with infection and shock or hypoperfusion
      criteria, the use of appropriate antibiotics in the first 3 h is the measure that
      has the greatest impact on survival. In addition, among patients with
      hyperlactatemia >4 mmol/L, the clearance of >10% of lactate during resuscitation
      is associated with better outcomes.

PMID- 30218960
TI  - Latent class analysis of the association between polycyclic aromatic hydrocarbon
      exposures and body mass index.
AB  - BACKGROUND: People experience multiple co-occurring exposures to environmental
      pollutants, but analyses of multiple exposures have rarely been reported.
      OBJECTIVES: We used latent class analysis to estimate co-exposures to multiple
      polycyclic aromatic hydrocarbons (PAH), and tested the associations of latent
      classes to body mass index. METHODS: We analyzed National Health and Nutrition
      Examination Survey (NHANES) 2013-2014 data. The sample included 2354 people aged
      6-80 years. Measures included seven urinary PAH metabolites, BMI, and demographic
      and behavioral covariates. People were classified into mutually exclusive latent
      classes characterized by unique profiles of multiple PAH exposures. These classes
      were used as categorical independent variables in weighted multiple regression
      models with BMI as the dependent measure. Models were analyzed overall and by age
      groups (6-19, 20-59, and 60 and over.) We compared results using latent classes
      to results using a summed PAH exposure measure. RESULTS: Five latent classes were
      identified. Two of these classes were significantly associated with higher BMI
      overall (p < .0001) and for the two youngest age groups. One of these classes was
      characterized by high multiple exposures across all PAHs, and one by moderate
      exposures but relatively high naphthalene and phenanthrene. The summed PAH score
      was associated with higher BMI only for the youngest age group. CONCLUSIONS:
      Persons experience multiple co-exposures to PAHs that are related to BMI and
      obesity across age groups. Latent class analysis provides information on higher
      order interactions among multiple chemicals that a summed score does not. Future
      work may apply this approach to other outcomes or types of co-exposures.

PMID- 30218961
TI  - Impairment of bisphenol F on the glucose metabolism of zebrafish larvae.
AB  - Bisphenol F (BPF) is a substitute of bisphenol A in the production of epoxy resin
      and polycarbonate. Its extensive use in consumer products leads to a wide human
      exposure at high levels. Although the adverse effects of BPF on animal health are
      of increasing public concern, its risks on systematic glucose metabolism and
      blood glucose concentrations still remain largely unknown. Using zebrafish larvae
      as the model animal, we investigated the disturbance of BPF exposure on glucose
      metabolism and the underlying mechanisms. Zebrafish larvae at 96 h post
      fertilization were exposed to 0.1, 1, 10, and 100 MUg/L of BPF for 48 h. Compared
      with the control group, glucose levels of larvae increased significantly in the
      10 and 100 MUg/L exposure groups, which are associated with enhancement of
      gluconeogenesis and suppression of glycolysis induced by high doses of BPF.
      Additionally, both mRNA expressions and protein levels of insulin increased
      significantly in the 10 and 100 MUg/L exposure groups, while transcription levels
      of genes encoding insulin receptor substrates decreased significantly in these
      groups, indicating a possibly decreased insulin sensitivity due to impairment of
      insulin signaling transduction downstream of insulin receptor. Further, compared
      with BPF alone, co-exposure of larvae to BPF and rosiglitazone, an insulin
      sensitizer, significantly attenuates increases in both glucose levels and mRNA
      expressions of a key gluconeogenesis enzyme. Our data therefore indicate
      impairing insulin signaling transduction may be the main mechanism through which
      BPF disrupts glucose metabolism and induces hyperglycemia. Results of the present
      study inform the health risk assessment of BPF and also suggest the use of
      zebrafish larvae in large-scale screening of chemicals with possible glucose
      metabolism disturbing effect.

PMID- 30218962
TI  - Indoor air pollution in rural north-east India: Elemental compositions, changes
      in haematological indices, oxidative stress and health risks.
AB  - Chronic smoke exposure, emitted by biomass fuel burning leads to many diseases,
      which are originated due to oxidative stress. The present study investigated the
      levels of PM2.5, PM10 and PM2.5 bound trace metals released during cooking with
      fuelwood and subsequent changes in haematological parameters along with oxidative
      stress in rural tribal women of northeast India exposed to wood smoke. The levels
      of PM2.5, PM10 and trace metals associated with PM2.5 (nickel, cobalt, manganese,
      zinc, cadmium, lead and copper) were measured. In addition, blood samples were
      analyzed for concentrations of different blood related parameters (haemoglobin,
      platelet count, red blood cells and white blood cells) and levels of antioxidants
      (reduced glutathione, superoxide dismutase, and catalase). Plasma malondialdehyde
      (MDA) was measured as a biomarker of lipid peroxidation. Health risk assessment
      was done to assess the potential risk posed by inhalation of fine particles
      emitted from cooking with fuel wood. Levels of both PM2.5 and PM10 were higher in
      wood users compared to LPG users during cooking period (644.4 +/- 368.3 ug/m3 vs
      50 +/- 23.8 ug/m3; 915 +/- 441.3 ug/m3 vs 83.3 +/- 33 ug/m3) and it exceeded the
      permissible limits of WHO. Levels of trace metals during the cooking period in
      fuel wood users were significantly higher than LPG users (p = 0.01). After
      controlling possible confounders, both platelet count and white blood cells (WBC)
      had a significant positive association with PM2.5and PM10. Similarly, haemoglobin
      had a negative association with both PM2.5 and PM10. Depleted levels of
      antioxidant enzymes and increase in lipid peroxidation (MDA) suggest a close
      association with pollutants released from wood smoke, indicating oxidative stress
      in women who used fuelwood for cooking. The total hazard quotient (HQ) of 0.11
      was within the acceptable limit (i.e., 1.0). The total excess lifetime cancer
      risk (ELCR) was 5.4 * 10-6 which is five times higher than the acceptable limit
      of 1.0 * 10-6. Individual carcinogenic risk of Ni (2.3 * 10-6) and Cd (3.1 * 10
      6) were also higher compared to acceptable limit. These results indicate that
      tribal women cooking with wood are at greater risk of developing cancer and also
      give support to the positive association between wood smoke and oxidative stress.

PMID- 30218963
TI  - Using solar cell to phytoremediate field-scale metal polluted soil assisted by
      electric field.
AB  - Eucalyptus globulus were used to remediate a real scale site endangered by e
      waste with electric fields supplied by solar cell and conventional storage
      battery. The capacity of the species to produce biomass, absorb pollutants and
      decontaminate metals, as well as the soil moisture of various layers under
      different treatments was compared. During the 3-month experiment, the output
      potential of solar cell influenced by weather conditions was less stable (ranging
      from 0 to 8.3 V) comparing with traditional power supply. Solar cell and storage
      battery stimulated the growth of the species from 5.92 in control to 7.21 and
      7.38 kg per plant, respectively, demonstrating their similar improvement effect.
      Electric fields of either power source increased the metal concentrations of
      plant roots and shoots in equal proportions and subsequently greatly promoted the
      efficiency to decontaminate pollutants. Relative to the control without electric
      field, solar cell and storage battery treatments reduced the soil moisture of
      each corresponding layer and consequently, alleviated the leaching risk. At the
      termination of the experiment, metals tended to distribute in the surface layer
      under electric field assisted phytoremediation either by solar cell or storage
      battery. Comparing with conventional battery, solar cell has similar effect on
      improving remediation and mitigating leaching risk, but is less energy consuming
      and easier to manage, especially under real scale field. Solar cell treatment was
      suggested to be a suitable supplementary means to improve phytoremediation
      efficiency.

PMID- 30218964
TI  - Optimized preparation of Phragmites australis activated carbon using the Box
      Behnken method and desirability function to remove hydroquinone.
AB  - In this study, preparation of Phragmites australis activated carbon (PAAC) was
      optimized and applied for the removal of hydroquinone from aqueous solution. The
      Box-Behnken surface design (33) was used to statistically visualize the
      interactions among microwave power (A), microwave radiation time (B) and the
      ingredient ratio (C) (H3PO4: P. australis powder, in g). The desirability
      function was utilized to simultaneously optimize the multi-response indicators. A
      regression analysis showed that the experimental data of BBD optimization
      experimental results fit well to a quadratic model. PAAC was characterized
      according to its morphology, structure and composition. Dynamic adsorption data
      showed that the best fit was obtained by a pseudo-second-order model and the
      Freundlich isotherm model. The maximum adsorption capacity for hydroquinone
      adsorption onto PAAC was 156.25 mg/g at 30 C and the adsorption mechanism may be
      attributed to multi-layer surface and chemisorption via donor-acceptor and
      coupling interaction of the electron. The present study showed that PAAC has the
      potential for use as a biosorbent for the adsorption treatment of water
      pollutants.

PMID- 30218965
TI  - Non-toxicity of nano alumina: A case on mung bean seedlings.
AB  - Wide use of Al2O3 nanoparticles (NPs) leading to their possible escape into
      environment and their interaction with living organisms demands immediate
      attention. We evaluated impact of nanoparticulate (Al2O3-NPs) and ionic (Al3+)
      forms of aluminium on early seedling growth of Vigna radiata. While Al3+
      inhibited growth of seedlings, Al2O3-NPs did not affect it negatively. Unlike
      enhancement in proline, malondialdehyde and H2O2 levels in roots and shoots
      induced by Al3+, these stress markers remained unaltered by Al2O3-NPs. No signs
      of membrane damage were recorded in roots of seedlings raised in presence of
      Al2O3-NPs; this was witnessed from insignificant electrolyte leakage and Evans
      blue uptake. Activities of antioxidant enzymes, i.e., superoxide dismustase,
      catalase, guaiacol peroxidase in root and shoot were enhanced by Al3+. However,
      they were unaffected by Al2O3-NPs. Al3+ enhanced levels of non-protein thiols,
      phenolics and ascorbate, with no alterations induced by Al2O3-NPs. These findings
      revealed that, Al2O3-NPs did not induce oxidative stress in seedlings. Seedlings
      raised in Al3+ showed higher uptake of Al than those grown in Al2O3-NPs; Al
      content was higher in roots. Al was not detected in shoots of seedlings grown in
      Al2O3-NPs. Lower translocation of Al in seedlings raised in Al2O3-NPs was due to
      adsorption/restriction of Al2O3-NPs on root surface. Al3+ caused ruptures on root
      epidermis of seedlings and inhibited root-hair formation, whereas no structural
      damage was caused by Al2O3-NPs. Our findings revealed that while ionic Al is
      highly toxic, nanoparticulate form of Al is non-toxic to growth of V. radiata.

PMID- 30218966
TI  - Polycyclic aromatic hydrocarbons in soil of the backfilled region in the Wuda
      coal fire area, Inner Mongolia, China.
AB  - The Wuda coal fire area in Inner Mongolia, China, has existed for 50 years and
      been controlled by digging and backfilling for many years. However, few studies
      have focused on its impact on the local environmental and ecological systems due
      to emission of organic contaminants from the backfilled region. In the study,
      topsoil samples were collected at a 0-5 cm depth from the backfilled region of
      the Wuda coal fire area, which has existed for five years. The samples were
      analyzed for 16 priority control contaminants, namely polycyclic aromatic
      hydrocarbons (PAHs), with a standard operation procedure and high-performance
      liquid chromatograph (HPLC). The results showed that the total mass contentration
      of 16 PAHs (?16PAHs) ranged from 279 to 8258 MUg kg-1, with an average value of
      2853 +/- 2948 ug kg-1, which exceeded the stipulated limit for heavily
      contaminated soil (1000 MUg kg-1). Among the 16 PAHs, 2- and 3-ring compounds
      accounted for more than half of ?16PAHs. Furthermore, the results show that the
      main contaminants were the naphthalene (Nap), phenanthrene (Phe), pyrene (Pyr),
      chrysene (Chr), and benzo[b]fluoranthene (BbF) in this area (24.8%, 51.1%, 3.9%,
      4.5%, and 5.7% of ?16PAHs, respectively). The diagnostic ratio of FLA/(FLA + PYR)
      exceeded 0.4 and IcdP/(IcdP + BghiP) was less than 0.5, indicating gentle
      smoldering or spontaneous combustion of coal fire, which differs from traditional
      coal burning. The environmental health risk or specifically the cancer risk (CR),
      calculated using the surface soil of the backfilled region, was 2.84 * 10-6 for
      adults and 1.01 * 10-6 for children, thus indicating potential cancer risks.
      Therefore, PAHs pollution in the surface soil of the backfilled region in the
      studied coal fire area is an issue that deserves urgent attention.

PMID- 30218967
TI  - Carcinogenic profile, toxicity and source apportionment of polycyclic aromatic
      hydrocarbons accumulated from urban road dust in Tokyo, Japan.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in urban environments.
      Urban road dust (URD) generated by traffic is an important PAH accumulator.
      Twelve priority PAHs in < 2000 um fraction of ten URD samples from Tokyo, Japan
      were characterized based on profile distributions, carcinogenicity, toxicity, and
      source apportionment by cluster analysis, biplot and diagnostic ratios. PAH
      concentrations (mg/kg dry weight) in arterial roads, highways, highway parking,
      highway drainage pit and residential area URD samples were 2.06-4.24, 0.25-3.37,
      3.44, 4.94, and 5.26 respectively, dominated by the ?4 rings (average 46%) and ?5
      + 6 rings (average 41%) PAHs. Biplot analysis revealed that the antecedent dry
      weather period, vehicle frequency and organic matter content were the dominant
      environmental factors governing PAH profiles of different road types. The total
      amount of carcinogenic PAHs in the residential URD (2.12 mg/kg) was higher than
      those in the arterial road (0.60-2.00 mg/kg) and highway (0.10-1.84 mg/kg) URD.
      Toxic equivalent concentrations (TECs) of residential, arterial road and highway
      URD were 0.54, (0.12-0.57), and (0.02-0.51) mg/kg, respectively. The dominant PAH
      sources were found to be petrogenic combustion in arterial road and highway URD,
      and pyrogenic combustion consisting of a mix of biomass, petroleum and traffic
      related sources in the residential and highway drainage pit samples. This is also
      the first study to find that TEC-based toxicity should not be taken as a measure
      of URD toxicity.

PMID- 30218968
TI  - Cloning, characterization and expression analysis of metallothioneins from
      Ipomoea aquatica and their cultivar-dependent roles in Cd accumulation and
      detoxification.
AB  - To explore the possible roles of metallothioneins (MTs) played in cadmium (Cd)
      accumulation of water spinach, three IaMT genes, IaMT1, IaMT2 and IaMT3 in a high
      shoot-Cd (T308) and a low-shoot-Cd accumulation cultivar (QLQ) were cloned,
      characterized, and quantitated. Gene expression analysis suggested that the
      expression of the IaMTs was differentially regulated by Cd stress in different
      cultivars, and T308 showed higher MTs expression overall. Furthermore, only shoot
      IaMT3 expression was cultivar dependent among the three IaMTs. Antioxidant
      analysis showed that the high production of IaMTs in T308 should be associated
      with its high oxidation resistance. The role of IaMTs in protecting against Cd
      toxicity was demonstrated in vitro via recombinant E. coli strains. The results
      showed that IaMT1 correlated with neither Cd tolerance nor Cd accumulation of E.
      coli, while IaMT2 conferred Cd tolerance in E. coli, IaMT2 and IaMT3 increased Cd
      accumulation in E. coli. These findings help to clarify the roles of IaMTs in Cd
      accumulation, and increase our understanding of the cultivar-dependent Cd
      accumulation in water spinach.

PMID- 30218969
TI  - Ultrasound-assisted dispersive liquid-liquid microextraction followed by ion
      mobility spectrometry for the simultaneous determination of bendiocarb and
      azinphos-ethyl in water, soil, food and beverage samples.
AB  - A sensitive and fast ultrasound-assisted dispersive liquid-liquid microextraction
      procedure combined with ion mobility spectrometry has been developed for the
      simultaneous extraction and determination of bendiocarb and azinphos-ethyl.
      Experimental parameters affecting the analytical performance of the method were
      optimized: type and volume of extraction solvent (chloroform, 150 uL), pH (9.0),
      type and volume of buffer (ammonium buffer pH = 9.0, 4.5 mL) and extraction time
      (3.0 min). Under optimum conditions, the linearity was found to be in the range
      of 2-40 and 6-100 ng/mL and the limits of detection (LOD) were 1.04 and 1.31
      ng/mL for bendiocarb and azinphos-ethyl, respectively. The method was
      successfully validated for the analysis of bendiocarb and azinphos-ethyl in
      different samples such as waters, soil, food and beverage samples.

PMID- 30218970
TI  - Green synthesis and optimization of nano-magnetite using Persicaria bistorta root
      extract and its application for rosewater distillation wastewater treatment.
AB  - The aim of this research is to synthesize magnetite nanoparticles, using
      Persicaria bistorta root extract as the reducing agent, and to test its
      adsorption properties in the treatment of rosewater distillation wastewater.
      Taking advantage of Taguchi method, effect of synthesis parameters, including
      molar concentration of FeCl2, concentration of plant extract, temperature, and pH
      on crystallite size and magnetization strength is studied. Based on the
      successful synthesis of magnetite nanoparticles and characterization experiments,
      Persicaria bistorta root extract can be considered as a proper alternative as the
      reducing agent. Data analysis shows that crystallite size and magnetization are
      positively correlated with concentration of FeCl2 and pH, while inversely related
      to temperature and independent of plant extract concentration. The optimum values
      achieved for concentration of FeCl2, temperature, and pH are 0.15 M, 70  degrees
      C, and 11, respectively, with the production of nanoparticles with magnetite size
      of 45.5 nm and magnetization value of 62.5 emu/g. In addition, the application of
      as-synthesized magnetite nanoparticles as an adsorbent for treatment of rosewater
      distillation wastewater proved its high adsorption capacity for chemical oxygen
      demand (COD) up to 149 mg/g. Adsorption data also shows a good fitness with
      Langmuir and Freundlich isotherm models.

PMID- 30218971
TI  - The metabolism distribution and effect of imidacloprid in chinese lizards
      (Eremias argus) following oral exposure.
AB  - Systematically evaluation of the metabolism, distribution and effect of
      imidacloprid in Chinese lizards (Eremias argus) were carried out following oral
      exposure. Imidacloprid-olefin-guanidine was prone to accumulate in the brain and
      caused potential neurotoxicity. Percutaneous and excretory excretions were the
      primary ways for the elimination of imidacloprid and its metabolites. Liver was
      the main site for hydroxy reduction and nitro-reduction metabolism of
      imidacloprid. The metabolism of imidacloprid was a complex process in which many
      metabolic enzymes participated. Aldehyde oxidase and CYP2C9 were the key enzymes
      in nitro-reduction process. CYP3A4 dominated the process of hydroxylation and
      desaturation. The increase in Glutathione S-transferase expression may be related
      to the removal of imidacloprid, but also related to the oxidative stress reaction
      that imidacloprid may cause in tissues, especially in the kidney. The findings
      enrich and supplement the knowledge of the environmental fate of imidacloprid in
      reptiles.

PMID- 30218972
TI  - Cephalic venous aneurysm in the wrist.
AB  - Venous aneurysms are benign vascular lesions usually located in the neck, lower
      extremity, and abdomen, but rarely in the upper extremity. There may be a mistake
      or delay in diagnosis because they are uncommon. We report a case of a healthy 54
      year-old man who had a cephalic venous aneurysm in his wrist that grew slowly
      over 20 years. The diagnosis was made on MRI and confirmed with excisional
      surgery. Radiologists should consider venous aneurysms in the differential when
      evaluating soft tissue masses as they will often be the first to make the correct
      diagnosis.

PMID- 30218973
TI  - Optimizing the deformation behavior of stent with nonuniform Poisson's ratio
      distribution for curved artery.
AB  - Stent implantation at a highly curved artery has always been a challenge,
      considering the relatively high chance of in-stent restenosis (ISR) caused by
      severe straightening effect and high strain energy over the vessel wall. In this
      paper, a novel optimization based design method was proposed to manipulate the
      deformation behavior of the common ring-and-link stent. By changing the location
      of the connection point between rings and links, traditional ring-and-link
      structure was modified to achiever tunable Poisson's ratio (PR). With the
      nonuniform cellular structure design method proposed in a previous study, PR
      distribution of the stent structure was optimized to achieve the desired
      curvature. As a result, the obtained stent structure with nonuniform PR could
      perfectly fit into the curved artery after expansion, without causing any obvious
      vessel straightening. To validate the proposed method, two different vessel
      models were introduced. Firstly, a short vessel with a constant curvature was set
      as the design objective, and both numerical and experimental tests were
      conducted. Further, a patient-specific vessel was applied. Both test results
      showed that optimized stents would cause much smaller vessel straightening.
      Moreover, vessels stented by the optimized structures had much lower stress
      concentration and strain energy. All those properties will decrease the
      possibility of ISR significantly.

PMID- 30218974
TI  - Influence of magnesium particles and Pluronic F127 on compressive strength and
      cytocompatibility of nanocomposite injectable and moldable beads for bone
      regeneration.
AB  - A novel one-step preparation of magnesium particles and Pluronic F127
      incorporated with calcium sulfate hemihydrate (CSH) and nano-hydroxyapatite (nHA)
      ready to use injectable or moldable beads was developed for bone tissue
      regeneration applications. The nanocomposite showed setting time less than 15
      min, very good injectability (75-85%) and good mechanical strength (52-80 MPa).
      Samples immersed in SBF showed controlled degradation (40-45% reduction in
      weight) in 28 days. The nanocomposite bone graft was cytocompatible against MG63
      osteosarcoma cells and increased the osteogenic gene expression by 2-3 folds.
      These results indicate that it can be a potential defect filling biomaterial for
      bone tissue regeneration at the fracture site.

PMID- 30218975
TI  - Effect of setting atmosphere on apatite cement resorption: An in vitro and in
      vivo study.
AB  - OBJECTIVES: The aim of this present study was to investigate the effect of
      setting atmosphere on replacement of apatite cement with new bone both in vitro
      and in vivo. MATERIAL AND METHODS: Apatite cement consisting of an equimolar
      mixture of tetracalcium phosphate and anhydrous dicalcium phosphate was mixed
      with distilled water and allowed to set at 37  degrees C and 100% relative
      humidity under 0%, 5%, and 100% CO2 atmospheres. X-Ray diffraction and Fourier
      Transform Infrared Spectroscopy were employed to confirm the carbonate apatite
      formation. Micro-CT and histological evaluation was made at 1 and 6 month(s)
      using twelve 10-week-old specific-pathogen-free male Wistar rats. RESULTS: B-type
      carbonate apatite was found when the apatite cement was set under 100% CO2 and 5%
      CO2. More carbonate apatite was formed in the case of 100% CO2 when compared with
      5% CO2, and none was formed under 0% CO2. Interestingly, unreacted tetracalcium
      phosphate was significant when apatite cement was set under 0% CO2, indicating
      the formation of Ca-deficient hydroxyapatite. When a bone defect of rat tibia was
      reconstructed in these conditions of apatite cement and sintered hydroxyapatite,
      replacement of the apatite cement was confirmed 6 months after implantation,
      whereas no replacement was observed in the case of sintered hydroxyapatite. The
      amount of replacement of apatite cement with bone was greater, on the order of
      100% CO2 and 5% CO2, followed by 0% CO2. CONCLUSION: The results obtained in the
      present study demonstrated that setting atmosphere clearly plays an important
      role in the replacement of set apatite cement with bone.

PMID- 30218976
TI  - Survival benefit, disease progression and quality-of-life outcomes of abiraterone
      acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate
      cancer: A network meta-analysis.
AB  - AIM: Androgen deprivation therapy (ADT) has long been the gold standard for
      patients with metastatic hormone-sensitive prostate cancer (mHSPC). Clinical
      trials have demonstrated significant survival benefits when docetaxel (DOC) or
      abiraterone acetate (AA) and prednisone (P) are added to ADT, necessitating
      comparison of these combination treatments. METHODS: A systematic review of
      randomised controlled trials (RCTs) of AA-/ADT-/DOC-containing treatment regimens
      in newly diagnosed patients with high-risk and/or high-volume mHSPC identified
      three RCTs (LATITUDE, CHAARTED and GETUG-AFU 15). Network meta-analyses (NMAs)
      using fixed effects Bayesian methods were performed to compare relative benefits
      of each treatment on overall survival (OS), radiographic progression-free
      survival (rPFS) and quality of life (QoL) measured by the Brief Pain Inventory,
      and the Functional Assessment of Cancer Therapy-Prostate questionnaire. One
      trial, STAMPEDE, was assessed in exploratory OS analyses. RESULTS: The hazard
      ratio (HR) for OS ranged from 0.85 to 0.92, with the Bayesian probability of AA +
      P + ADT being better than DOC + ADT ranging between 72% and 87%. For rPFS, the HR
      ranged between 0.71 and 0.76 (Bayesian probability range: 93%-97%). Exploratory
      analyses including STAMPEDE found similar trends. AA + P + ADT also showed
      improved QoL compared with DOC + ADT for at least 1 year of therapy, with results
      being more pronounced at 3 months. CONCLUSION: Our findings suggest that AA + P +
      ADT is at least as effective as DOC + ADT in reducing the risk of death in men
      with mHSPC and better at preventing disease progression and improving QoL. The
      NMA provides useful insights to clinicians and other decision-makers on the
      relative efficacy of treatment options for men with mHSPC.

PMID- 30218977
TI  - Notch pathway inhibition with LY3039478 in soft tissue sarcoma and
      gastrointestinal stromal tumours.
AB  - BACKGROUND: LY3039478 is an orally bioavailable selective Notch inhibitor. This
      phase 1a/b trial evaluated the safety, pharmacokinetics and antitumour activity
      of LY3039478 in patients with soft tissue sarcoma (STS) and gastrointestinal
      stromal tumour (GIST). METHODS: This multipart, phase 1 trial enrolled patients
      with refractory advanced/metastatic STS and GIST, measurable disease, Eastern
      Cooperative Oncology Group <=1 and baseline tumour tissue. Eligible patients
      received LY3039478 50mg/75 mg three times per week, for 28-day cycle until
      disease progression. Safety assessments were based on Common Terminology Criteria
      for Adverse Events, V4.0. Tumour responses were assessed using Response
      Evaluation Criteria in Solid Tumours (RECIST 1.1) and Choi criteria. Primary
      objectives were to confirm the recommended phase 2 dose of LY3039478 and document
      the antitumour activity. Secondary objectives were safety and toxicity,
      pharmacokinetics (PK), progression-free survival (PFS) and overall survival (OS).
      RESULTS: Sixty-nine patients were enrolled and received LY3039478 (27 males, 42
      females; median age 58, range 31-78). 16/37 (43%) patients with evaluable samples
      were positive for Notch 1 immunohistochemistry. Per RECIST 1.1, in leiomyosarcoma
      (LMS) group (n = 29), ten (36%) had stable disease (SD) and one (4%) had
      unconfirmed partial response (PR). In GIST group (n = 13), four (31%) had SD.
      Among other STS subtypes (n = 27), one patient with angiosarcoma had unconfirmed
      PR, six (21%) had SD. Median PFS was 1.9 months (95% confidence interval:1.6-3.3)
      for LMS, 1.9 months (0.3-6.1) for GIST and 1.7 months (1.4-2.2) for other STS
      groups. Median OS was 7.4 months (4.3-non-evaluable [NE]) for LMS, 16.5 months
      (3.9-16.5) for GIST and 5.6 months (3.4-NE) for other STS groups. Most common
      adverse events were diarrhoea, nausea, vomiting and decreased appetite.
      CONCLUSION: LY3039478 suggested a modest clinical activity in patients with STS
      and GIST and had a manageable safety profile.

PMID- 30218978
TI  - A theory of reactant-stationary kinetics for a mechanism of zymogen activation.
AB  - A theoretical analysis is performed on the nonlinear ordinary differential
      equations that govern the dynamics of a reaction mechanism of zymogen activation.
      The reaction consists of a primary non-observable zymogen activation reaction
      that it is coupled to an indicator (observable) reaction. The product of the
      first reaction is the enzyme of the indicator reaction, and both reactions are
      governed by the Michaelis-Menten reaction mechanism. Using singular perturbation
      methods, we derive asymptotic solutions that are valid under the quasi-steady
      state and reactant-stationary assumptions. In particular, we obtain closed form
      solutions that are analogous to the Schnell-Mendoza equation for Michaelis-Menten
      type reactions. These closed-form solutions approximate the evolution of the
      observable reaction and provide the mathematical link necessary to measure the
      enzyme activity of the non-observable reaction. Conditions for the validity of
      the asymptotic solutions are also derived, and we demonstrate that these
      asymptotic expressions are applicable under reactant-stationary kinetics.

PMID- 30218979
TI  - Linoleic acid reduces vascular reactivity and improves the vascular dysfunction
      of the small mesentery in hypertension.
AB  - We aimed to investigate the effect of linoleic acid (LA) treatment on the blood
      pressure and function of mesenteric resistance arteries (MRA) in spontaneous
      hypertensive rats (SHR). Male SHR were treated daily with LA (15 mg/kg) or
      vehicle (control) for 15 days. Compared with controls, LA treatment decreased
      blood pressure and showed the following in MRA: (1) increased lumen and external
      diameter, (2) decreased wall:lumen ratio and wall thickness, (3) decreased
      stiffness and (4) less collagen deposition. LA treatment reduced the contractile
      response to phenylephrine, although there were no changes observed in MRA in
      regard to the acetylcholine or sodium nitroprusside responses. Incubation with L
      NAME left-shifted the reactivity to phenylephrine only in the MRA treated group,
      suggesting that LA treatment can improve NO bioavailability. This result was
      accompanied by an increase "in situ" NO production. Incubation with tiron
      decreased vascular reactivity to phenylephrine in MRA in LA rats, which was
      accompanied by decreased superoxide anion production. Moreover, incubation with
      indomethacin (non-selective COX inhibitor, 10 MUM), NS 398 (COX-2 specific
      inhibitor, 1 MUM), furegrelate (TXA2 synthase inhibitor, 1 MUM), SQ 29.548 (TP
      receptor antagonist, 1 MUM) and SC 19220 (EP1 receptor antagonist, 10 MUM)
      reduced the vasoconstrictor responses to phenylephrine in MRA in the treated
      group. These results were accompanied by a reduction in COX-2 protein expression.
      In conclusion, these findings show that LA treatment decreases blood pressure. In
      addition, the improvement of endothelial dysfunction and structural changes in
      this hypertension model may be responsible for the reduction in blood pressure.

PMID- 30218981
TI  - Drug-in-mucoadhesive type film for ocular anti-inflammatory potential of
      amlodipine: Effect of sulphobutyl-ether-beta-cyclodextrin on permeation and
      molecular docking characterization.
AB  - Mucoadhesive type ocular film has been prepared for studying the anti
      inflammatory potential of amlodipine (AML) on carrageenan-induced rabbit model
      and the effect of sulphobutyl-ether-beta-cyclodextrin on corneal permeation was
      tested. Hydroxypropyl methylcellulose (HPMC) ocular film was prepared after
      complexation of amlodipine with beta-cyclodextrin, (BCD), hydroxypropyl beta
      cyclodextrin (HPCD), and sulfobutylether beta-cyclodextrin (SBCD). The film
      without cyclodextrin showed a maximum swelling, and erosion to the highest
      extent. Both drug release and permeation were highly diffusion controlled and
      highest improvement was observed with SBCD due to increased dissolution, compared
      to other formulations with or without cyclodextrin. Highest binding energy and
      highest extent of amorphization were noticed in the SBCD film formulation.
      Improved amlodipine release in-vitro and ocular permeation were found by the HPMC
      film formulation after complexation of the drug with cyclodextrins wherein SBCD
      exhibited both to the highest extent. Binary and ternary systems molecular
      docking studies confirmed the lowest energy of binding between amlodipine and BCD
      compared to HBCD and SBCD. Signs of acute inflammation were mitigated within 2 h
      of film application in the cul-de-sac. Presence of sulphobutyl-ether beta
      cyclodextrin in the amlodipine-HPMC film can improve ocular permeation
      significantly and could be utilized as mucoadhesive type formulation for anti
      inflammatory activity.

PMID- 30218980
TI  - Myeloperoxidase deficiency attenuates systemic and dietary iron-induced adverse
      effects.
AB  - Iron deficiency is routinely treated with oral or systemic iron supplements,
      which are highly reactive and could induce oxidative stress via augmenting the
      activity of proinflammatory enzyme myeloperoxidase (MPO). To investigate the
      extent to which MPO is involved in iron-induced toxicity, acute (24 h) iron
      toxicity was induced by intraperitoneal administration of FeSO4 (25 mg/kg body
      weight) to MPO-deficient (MpoKO) mice and their wild-type (WT) littermates. Acute
      iron toxicity was also assessed in WT mice pretreated with an MPO inhibitor, 4
      aminobenzoic acid hydrazide. Systemic iron administration up-regulated
      circulating MPO and neutrophil elastase and elevated systemic inflammatory and
      organ damage markers in WT mice. However, genetic deletion of MPO or its
      inhibition significantly reduced iron-induced organ damage and systemic
      inflammatory responses. In contrast to the acute model, 8 weeks of 2% carbonyl
      iron diet feeding to WT mice did not change the levels of circulating MPO and
      neutrophil elastase but promoted their accumulation in the liver. Even though
      both MpoKO and WT mice displayed similar levels of diet-induced hyperferremia,
      MpoKO mice showed significantly reduced inflammatory response and oxidative
      stress than the WT mice. In addition, WT bone-marrow-derived neutrophils (BMDN)
      generated more reactive oxygen species than MPO-deficient BMDN upon iron
      stimulation. Altogether, genetic deficiency or pharmacologic inhibition of MPO
      substantially attenuated acute and chronic iron-induced toxicity. Our results
      suggest that targeting MPO during iron supplementation is a promising approach to
      reduce iron-induced toxicity/side effects in vulnerable population.

PMID- 30218982
TI  - Manganese dioxide Nanorods/electrochemically reduced graphene oxide
      nanocomposites modified electrodes for cost-effective and ultrasensitive
      detection of Amaranth.
AB  - A novel manganese dioxide nanorods-electrochemically graphene oxide
      nanocomposites modified glassy carbon electrode (MnO2NRs-ErGO/GCE) was developed
      for the rapid and sensitive detection of Amaranth in foodstuffs. The morphology,
      structure and composition of MnO2NRs, ErGO, and MnO2/ErGO were characterized by
      SEM and XRD. The electrochemical behavior of Amaranth on the bare GCE, ErGO/GCE,
      and MnO2NRs-ErGO/GCE were investigated by cyclic voltammetry and electrochemical
      impedance spectroscopy. The voltammetric conditions (including pH, scan rate,
      accumulation potential as well as time) were optimized systematically. Due to
      large electrochemical active area and low charge transfer resistance, the MnO2NRs
      ErGO/GCE exhibited a great enhancement effect on the oxidation of Amaranth, and
      significant increased the oxidation peak current ipa (approximately 38-fold
      increase compared to that of bare GCE). Under the optimum voltammetric
      conditions, the ipa varied linearly with Amaranth concentration in the range of
      0.02 MUM-10 MUM, and 10 MUM-400 MUM with a low detection limit of 1.0 nM (S/N =
      3). Moreover, satisfactory results were obtained in the analysis of real samples.
      Together with the merits of rapidness, cost-effectivity, high sensitivity and
      selectivity, the result suggests the proposed MnO2NRs-ErGO/GCE have broad
      application prospects on the sensitive detection of Amaranth in various real
      samples.

PMID- 30218983
TI  - Skin-permeable liposome improved stability and permeability of bFGF against skin
      of mice with deep second degree scald to promote hair follicle neogenesis through
      inhibition of scar formation.
AB  - Excessive deposition of extracellular matrix (ECM) usually resulted in scar
      formation during wound healing, which caused skin dysfunction, such as hair loss.
      Basic fibroblast growth factor (bFGF) was very helpful for promoting hair
      follicle neogenesis and regulating the remodeling of ECM during wound healing.
      Because of its poor stability in wound fluids and low permeability against the
      dense wound scar, the repairing quality of bFGF on wound was hindered largely in
      clinical practice. To overcome these drawbacks, herein, a novel liposome with
      silk fibroin hydrogel core (bFGF-SF-LIP) was firstly prepared to stabilize bFGF,
      followed by insertion of laurocapam, a permeation enhancer, into the liposomal
      membrane to construct a skin-permeable liposome (SP-bFGF-SF-LIP). The
      encapsulated efficiency of bFGF was reaching to nearly 90% when ratio of
      drug/lipids above 1:300, and it activity was not compromised by laurocapam. SP
      bFGF-SF-LIP exhibited a hydrodynamic diameter of 103.3 nm and Zeta potential of 
      2.31 mV. The stability of the encapsulated bFGF in wound fluid was obviously
      enhanced. After 24 h of incubation with wound fluid containing MMP-9, the
      remaining bFGF was as high as 65.4 +/- 0.5% for SP-bFGF-SF-LIP, while only 2.1 +/
      0.2% of free bFGF was remained. The skin-permeability of bFGF was significantly
      enhanced by SP-bFGF-SF-LIP and most of the encapsulated bFGF penetrated into the
      dermis. After treatment with SP-bFGF-SF-LIP, the morphology of hair follicle at
      wound zone was obviously improved and the hair regrew on the deep second scald
      mice model. The therapeutic mechanism was highly associated with inhibiting scar
      formation and promoting vascular growth in dermis. Conclusively, SP-bFGF-SF-LIP
      may a potential option to improve wound healing with high-quality.

PMID- 30218984
TI  - Surface and swelling properties of mucoadhesive blends and their ability to
      release fluconazole in a mucin environment.
AB  - The aim of this study is to characterize the matrices for the controlled release
      of fluconazole and to expand the knowledge of their physicochemical properties
      that influence the process of mucoadhesion. Polymeric carriers of fluconazole
      were prepared using the following mucoadhesive polymers: Carbopol 974 P NF,
      Noveon AA-1, HPMC, HEC, chitosan and film-forming polymer Kollidon VA 64. The
      potential mucoadhesive properties of the polymers and their blends were evaluated
      by measuring the wettability and then calculating the surface free energy defined
      by OWRK and vOCG models, determining the polar and dispersion forces, spreading
      coefficients and work of adhesion of polymers and their blends with fluconazole
      in the form of tablets. Prepared tablets were characterized by swelling capacity
      and in vitro drug release to estimate the amount of fluconazole release from
      selected polymer blends. The study of drug release from selected blends both in
      simulated saliva fluid (pH = 6.8) and in simulated vaginal fluid (pH = 4.2)
      containing mucin confirmed the ability of polymeric carriers to continuously
      deliver drug over a period of about 8 h.

PMID- 30218985
TI  - A novel electrochemical sensor based on electrode modified with gold
      nanoparticles and molecularly imprinted polymer for rapid determination of
      trazosin.
AB  - A novel molecularly imprinted polymer sensor for fast and direct determination of
      trazosine (TR) was studied. The voltammetric sensor based on molecularly
      imprinted polymer (MIP) with disposable gold nanoparticles modified screen
      printed carbon electrode (MIP/AuNPs/SPCE) is developed for the determination of
      TR. Under the optimum conditions, the peak current of the sensor and TR
      concentration showed a good linear relationship over the range from 2.0 to 250.0
      MUM, with a low detection limit (S/N = 3) of 0.3 MUM. The modified electrode
      demonstrated good electrocatalytic properties toward the oxidation of TR. This
      sensor selectively detected TR even in the presence of high concentration of
      similar compounds and MIP/AuNPs/SPCE was also confirmed successfully for the
      determination of TR in the various real samples including human blood serum,
      urine and trazosin tablet.

PMID- 30218986
TI  - "I'm not in this alone" the perspective of parents mediating a physical activity
      intervention for their children with autism spectrum disorder.
AB  - BACKGROUND AND AIMS: Web-based, parent-mediated interventions have shown to be
      beneficial for children with autism spectrum disorder (ASD) in a variety of
      domains. We aimed to examine how parents of children with ASD perceive mediating
      a physical activity intervention delivered via a private Facebook group. METHODS:
      Thirteen families participated in a four-week trial of Project CHASE. Inductive
      thematic analysis of semi-structured interviews and interactions within the
      Facebook group were conducted to elicit the perspective of the parents. OUTCOMES
      AND RESULTS: Thematic analysis resulted in three themes emerging: (1)
      'Remembering to Act' encompassed the participants' perspectives of Project CHASE
      as being an intervention that reminded them of the importance of physical
      activity, and served as a prompt for them to take action; (2) 'A sharing
      community' included the subthemes of 'sharing success and struggles' and 'sharing
      ideas'; and, (3) 'Taking control: possibilities and problems' encapsulates the
      dichotomy between participants who spoke of embracing and rising to the challenge
      of taking control, with the parents who spoke of the need for more support,
      direction, and guidance. CONCLUSION AND IMPLICATION: The current study suggests
      parent-mediated, web-based interventions may have the potential for improving the
      effectiveness of physical activity interventions for children with ASD.

PMID- 30218987
TI  - In-situ grown manganese silicate from biomass-derived heteroatom-doped porous
      carbon for supercapacitors with high performance.
AB  - Supercapacitor performance is reported for manganese silicate hybridized carbon
      materials (MnSi-C) that is derived from natural bamboo leaves. The in-situ
      generated manganese silicate is in good distribution by a simple hydrothermal
      treatment without the addition of another controlling agent. We also study the
      performance of MnSi-C as a single electrode and a cathode for fabrication of
      asymmetric supercapacitor device with a Ni(OH)2 anode. Remarkably, the single
      electrode MnSi-C-3 delivered a capacity of 162.2 F g-1 at a current density of
      0.5 A g-1. The cyclic performance of single electrode MnSi-C-3 maintains high
      capacitance retention of 85% after 10,000 cycles of charge-discharge. By
      assembled MnSi-C-3 with Ni(OH)2, the asymmetric supercapacitor device shows a
      capacity of 438.5 mF cm-2 at a scan rate of 4 mA cm-2. The device exhibits an
      optimal electrochemical performance with an energy density of 3 mWh cm-3 (24.6 Wh
      kg-1) and power density of 130.4 mW cm-3 (604.8 W kg-1). A reasonable mechanism
      of in-situ generated manganese silicate on the surface of carbon is proposed
      based on the experimental data and existed theories. This MnSi-C nanocomposite
      proves to be a promising electrode material for high energy supercapacitor.

PMID- 30218988
TI  - Assessing omniphobicity by immersion.
AB  - HYPOTHESIS: Coating-free approaches to achieve liquid repellent, or omniphobic,
      surfaces could exploit inexpensive intrinsically wetting materials, such as
      polyethylene terephthalate and nylon, for applications such as liquid-vapor
      extraction and drag reduction. However, it is not clear whether the existing
      criteria for assessing coating-based omniphobicity, based on contact angles,
      would be reliable for coating-free approaches, especially considering localized
      defects/damages during manufacturing and usage. EXPERIMENTS: We assessed the
      omniphobicity of silica surfaces adorned with arrays of doubly reentrant pillars,
      cavities, and hybrid designs with sessile drops and on immersion in water and
      hexadecane through contact angle goniometry and confocal microscopy. FINDINGS: We
      demonstrate that the assessment of omniphobicity of surfaces derived from
      intrinsically wetting materials can be misleading, if solely based on the
      measurement of contact angles. Specifically, localized defects in microtextures
      consisting of pillars may lead to the spontaneous loss of omniphobicity and
      detecting them through contact angles can be difficult. We also demonstrate that
      the immersion of those surfaces into probe liquids may serve as a simple and
      quick 'litmus' test for omniphobicity. Thus, immersion as the additional
      criterion for omniphobicity might prove itself useful in the context of large
      scale manufacturing.

PMID- 30218989
TI  - In-situ synthesis of AgNbO3/g-C3N4 photocatalyst via microwave heating method for
      efficiently photocatalytic H2 generation.
AB  - This paper is designed for elevating the photocatalytic H2-evoultion performance
      of g-C3N4 through the modification of AgNbO3 nanocubes. Via the microwave heating
      method, g-C3N4 was in-situ formed on AgNbO3 surface to fabricate a close contact
      between the two semiconductors in forty minutes. X-ray diffraction (XRD), Fourier
      transform-infrared (FT-IR), X-ray photoelectron spectroscopy (XPS) experiments
      were performed to confirm the binary structure of the synthesized AgNbO3/g-C3N4
      composite. N2-adsorption and visible diffuse reflection spectroscopy (DRS)
      analyses indicated that the addition of AgNbO3 to g-C3N4 showed nearly negligible
      influence on the specific surface area and the optical property.
      Photoluminescence (PL) spectroscopy experiment suggested that the AgNbO3/g-C3N4
      displayed reduced PL emission and longer lifetime of photoexcited charge carriers
      than g-C3N4, which could be ascribed to the suitable band potential and the
      intimate contact of g-C3N4 and AgNbO3. This result was also confirmed by the
      transient photocurrent response experiment. The influence of the enhanced charge
      separation was displayed in their photocatalytic reaction. AgNbO3/g-C3N4 sample
      showed enhanced performance in photocatalytic H2-generation under visible light
      illumination. The H2-evolution rate is determined to be 88 MUmol.g-1.h-1, which
      reaches 2.0 times of g-C3N4. This study provides a feasible and rapid approach to
      fabricate g-C3N4 based composite.

PMID- 30218990
TI  - Mussel-inspired antifouling magnetic activated carbon for uranium recovery from
      simulated seawater.
AB  - Undesirable bio-adhesion of microalgae on adsorbent can influence its adsorption
      capacity. In this report, we fabricated a novel mussel-inspired antifouling
      magnetic activated carbons which derived orange peel by integrated biosorption
      pyrolysis process (MACs@PDA-Ag), via co-functionalization of poly-dopamine (PDA)
      and Ag nanoparticles (AgNPs), for the recovery of uranium (VI) from simulated
      seawater with antimicrobial adhesion performance; this process did not require an
      additional reducing agent. The effect of pH, concentration, contact time, fouling
      test against nitzschia closterium f.minutissima (GY-H8) were studied. Compared
      with MACs (632.91 mg/g at pH 7.0), the calculated maximum adsorption capacity of
      MACs@PDA-Ag increased to 657.89 mg/g at pH 8.0 and showed good recyclability.
      These data all fitted well with the Langmuir and pseudo-second order models. The
      possible removal mechanism by XPS is chelation (catechol hydroxyls, amine/imine
      units, the metal-oxygen and carboxylic) with uranium (VI). The antifouling tests
      indicated that the AgNPs-modified materials displayed the antimicrobial adhesion
      behavior, and the viability of the microorganism was not impacted. Thereby, the
      direct deposition of AgNPs onto the adsorbent has shown great potential for
      uranium (VI) recovery with an antifouling benefit and is environmentally
      friendly.

PMID- 30218991
TI  - Mid- and Long-Term Outcomes of Total Arterial Myocardial Revascularization in
      Patients Aged 70 Years and Older: A Single-Center Experience.
AB  - BACKGROUND:  Patients receiving arterial grafts have superior late survival after
      coronary artery bypass graft (CABG) surgery. The aim of our study was to evaluate
      the mid- and long-term results of total arterial (TA) revascularization in the
      elderly. METHODS:  Between January 2005 and December 2012, a retrospective study
      on age-, gender-, and EuroSCORE-matched patients aged 70 years and older was
      performed. Altogether, 356 patients who received isolated CABG were assigned to
      either TA group or control (CON) group. RESULTS:  No significant differences were
      noted in regard to preoperative risk factors. The number of distal anastomoses
      was significantly higher in the CON group (3.6 +/- 0.6 vs. 2.9 +/- 0.8; p <
      0.001). Postoperatively, no significant differences were noted in regard to
      morbidity or mortality. There were no significant differences in mortality rate
      at 1 year (5.6 vs. 5.2%; p = 0.98), or 5 years (9.0 vs. 12.1%; p = 0.39) between
      both groups. However, the TA group was associated with significantly higher rate
      of event-free survival (p = 0.017). CONCLUSION:  This study suggests that TA
      revascularization is an effective procedure. Lower rates of late cardiac events
      encourage the use of this concept for the elderly.

PMID- 30218992
TI  - Complex Valve Surgery in Elderly Patients: Increasingly Necessary and
      Surprisingly Feasible.
AB  - OBJECTIVES:  The increasing proportion of elderly patients in cardiac surgery
      poses additional challenges for the clinical management and leads to a higher
      operative risk due to multiple comorbidities of these patients. We reviewed the
      outcome of patients who were 75 years and older and underwent complex multiple
      valve surgery at our institution. METHODS:  A retrospective review was performed
      to identify patients who were 75 years and older and underwent multiple valve
      surgery between January 2011 and May 2016 at our institution. Patients were
      assigned to one out of four subgroups: combined aortic and mitral valve surgery
      (group AM), aortic and tricuspid valve surgery (group AT), mitral and tricuspid
      valve surgery (group MT), and aortic, mitral, and tricuspid valve surgery (group
      AMT). RESULTS:  A total of 311 patients underwent multiple valve surgery, of whom
      119 (38.3%) were 75 years and older (median: 78 [25th-75th quartile: 76-80]). The
      estimated operative mortality (EuroSCORE II) in the overall cohort was 10.7%. The
      observed 30-day mortality was 4.2% (7% in group AM, 0% in group AT, 2.2% in group
      MT, 3.8% in group AMT; p = 0.685). Main complications were reexplorative surgery
      in 16%, adverse cerebrovascular events in 6.7%, prolonged mechanical ventilation
      in 10.1%, renal replacement therapy in 15.1%, nosocomial pneumonia in 15.1%, and
      pacemaker implantation in 18.5%. CONCLUSIONS:  This study demonstrates the
      feasibility of complex multiple valve surgery in elderly patients. The observed
      perioperative mortality was lower than predicted. However, we observed a
      substantial rate of adverse events; therefore, careful patient selection is
      required in this high-risk patient population.

PMID- 30218993
TI  - Neurovascular Anatomy at the "Box Junction": Considerations in the Anterolateral
      Thigh Flap.
AB  - BACKGROUND:  The anterolateral thigh (ALT) perforator flap is one of the most
      widely used flaps in reconstructive microsurgery. This study investigated a
      previously unexplored and clinically relevant aspect of perforator anatomy: the
      "box junction" (BxJn), the point at which the perforator arises from its source
      vessel. Negotiating the BxJn can be a challenging and time-consuming step in flap
      harvest, due to the neurovascular structures in the area which must be protected
      from injury. However, as the presence and location of these structures have yet
      to be clearly defined, painstaking exploration is necessary on each occasion.
      Knowledge of BxJn anatomy could allow surgeons to harvest the ALT flap more
      rapidly and safely. METHODS:  We dissected 20 cadaveric thighs and identified
      perforators to the ALT region and investigated the neurovascular anatomy at their
      BxJns. RESULTS:  In 51 BxJns, two clinically relevant vascular structures were
      identified: an intramuscular artery arising from the perforator (23, 45% of
      cases) and a "deep" artery to the underlying muscle arising from the source
      vessel (29, 57% of cases). We confirmed the consistent presence of motor nerve
      branches and describe one previously unreported, clinically significant
      variation, in which the nerve to vastus lateralis crosses the BxJn (12, 24% of
      cases); 36, 71% of BxJns contained at least one vascular and one neural
      structure. CONCLUSIONS:  Our study confirms that the BxJn is a site of
      potentially complex and challenging neurovascular anatomy for the surgeon. Based
      on these results, we propose an algorithm to guide inexperienced surgeons in
      negotiating this area.

PMID- 30218994
TI  - Outcomes for individuals turned down for living kidney donation.
AB  - BACKGROUND: A better understanding of the consequences of being turned down for
      living kidney donation could help transplant professionals to counsel individuals
      considering donation. METHODS: In this exploratory study, we used survey
      instruments and qualitative interviews to characterize nonmedical outcomes among
      individuals turned down for living kidney donation between July 1, 2010 and
      December 31, 2013. We assembled a comparator group of kidney donors. RESULTS:
      Among 83 turned-down donors with contact information at a single center, 43 (52%)
      participated in the study (median age 53 years; 53% female; 19% black). Quality
      of life, depression, financial stress, and provider empathy scores were similar
      between individuals turned down for donation (n = 43) and donors (n = 128).
      Participants selected a discrete choice response to a statement about the overall
      quality of their lives; 32% of turned-down donors versus 7% of donors (P < 0.01)
      assessed that their lives were worse after the center's decision about whether
      they could donate a kidney. Among turned-down donors who reported that life had
      worsened, 77% had an intended recipient who was never transplanted, versus 36%
      among individuals who assessed life as the same or better (P = 0.02). In
      interviews, the majority of turned-down donors reported emotional impact,
      including empathy, stress, and other challenges, related to having someone in
      their lives with end-stage kidney disease. CONCLUSIONS: Generic instruments
      measuring quality of life, depression, financial stress, and provider empathy
      revealed no significant differences between kidney donors and turned-down donors.
      However, qualitative interviews revealed preliminary evidence that some turned
      down donors experienced emotional consequences. These findings warrant
      confirmation in larger studies.

PMID- 30218995
TI  - Molecular Characterization of a Fungus Producing Membrane Active Metabolite and
      Analysis of the Produced Secondary Metabolite
AB  - Background: The majority of studies on soil Aspergillus concern the isolation and
      characterization of the antimicrobial compounds produced by this organism. Our
      previous studies indicated an isolated Aspergillus strain soil to be of interest,
      and this subject is further studied here. Methods: Soil samples of various
      locations in Iran were collected. Extract from Aspergillus sp. culture was
      obtained using ethyl acetate fractionation. Antimicrobial activity testing was
      performed using broth microdilution assay against Escherichia coli, Candida
      albicans, and Staphylococcus aureus microorganisms. One metabolite PA3-d10 was
      isolated from these active extracts and identified using thin layer
      chromatography, preparative thin-layer chromatography, HPLC, 1HNMR (proton
      nuclear magnetic resonance), 2D NMR and LC-MS (liquid chromatography-mass
      spectrometry). Results: According to morphological and biochemical properties as
      well as ITS rDNA sequencing, we identified an isolate of Aspergillus flavus. The
      ethyl acetate fraction of the fermentation medium contained membrane active
      metabolites that showed antimicrobial effects against different bacterial and
      yeast indicator strains. One metabolite from these active extract was finally
      identified. Conclusion: Membrane active fraction produced by Aspergillus strain
      in this research demonstrated antimicrobial activities against bacteria and yeast
      strains. Therefore, this metabolite can be considered as a potential
      antimicrobial membrane active agent.

PMID- 30218996
TI  - Study Break: Cell Timer/Cell Clock

PMID- 30218997
TI  - Simvastatin Attenuates Hippocampal MMP-9 Expression in the Streptozotocin-Induced
      Cognitive Impairment
AB  - Background: Matrix metalloproteinase-9 (MMP-9) expression has been implicated in
      molecular mechanisms of neurodegenerative disorders, and its abnormal level has
      been reported in Alzheimer's disease (AD). Some protective mechanisms of statins
      against neurodegeneration might be mediated by the inhibition of MMP-9
      expression. Here, we investigated the effect of simvastatin, on the hippocampal
      MMP-9 expression in the context of AD. Methods: We examined the influence of
      three-week simvastatin (5 mg/kg) administration on hippocampal MMP-9 expression
      in a rat model of cognitive decline induced by streptozotocin (STZ). Spatial long
      term memory and MMP-9 expression were assessed by Morris water maze (MWM) test
      and quantitative polymerase chain reaction, respectively. Results: The results
      showed a decline in the learning and memory in STZ group when compared with the
      control group. The MMP-9 was up-regulated (1.41 +/- 0.2 vs. 0.980 +/- 0.02, p <
      0.05), and cresyl violet staining showed hippocampal cell damage in STZ group
      compared with the control group. Simvastatin prevented the up-regulation of MMP-9
      (1.05 +/- 0.05 vs. 1.41 +/- 0.2, p < 0.05), improved spatial memory impairment
      and attenuated hippocampal cell damage. Furthermore, we found a negative
      correlation (r = 0.77) between MMP-9 expression and cognitive function.
      Conclusion: Our findings suggest that the neuroprotective influence of
      simvastatin in battle to cognitive impairment is mediated in part by the
      modulation of MMP-9 expression. The reduction of MMP-9 expression in simvastatin
      treated animals is in correlation with the improvement of cognitive functions.
      Understanding the protective mechanism of simvastatin will shed light on more
      efficient therapeutic modalities in AD.

PMID- 30218998
TI  - Evolutions of packing properties of perfect cylinders under densification and
      crystallization.
AB  - Cylindrical particles are ubiquitous in nature and industry, and a cylinder is a
      representative shape of rod-like particles. However, the disordered packing
      results of cylinders in previous studies are quite inconsistent with each other.
      In this work, we obtain the MRJ (maximally random jammed) packings and the MDRPs
      (maximally dense random packings) of perfect cylinders with the aspect ratio
      (height/diameter) 0.2 <= w <= 6.0 using the ASC (adaptive shrinking cell)
      algorithm and the IMC (inverse Monte Carlo) method, respectively. The optimal
      aspect ratio corresponding to the maximal packing density is w = 0.9 in the MRJ
      state, while the value is w = 1.2 in the MDRP state. Then we investigate the
      evolutions of packing properties of perfect cylinders under densification and
      crystallization. We compare the different final packing states generated via the
      two methods with different compression rates and order constraints. In the
      densification procedure, we generate jammed and random packings of cylinders with
      various compression rates via the ASC and IMC method, respectively. When
      decreasing the compression rate, we find that the packing density increases but
      the optimal w remains the same in both methods. In the crystallization procedure,
      the order constraint in the IMC method is gradually released which means the
      degree of order in the packings is allowed to increase, and we find that the
      optimal w shifts from 1.2 to 0.9 while the packing density increases as well.
      Meanwhile, the random packings evolve into the jammed packings in the
      crystallization procedure which reflects the competition mechanism between the
      randomness and jamming. These results also indicate that the optimal w is solely
      related to the degree of order in the cylinder packings but not determined by the
      protocol or packing density. Furthermore, a uniform shape elongation effect on
      the random-packing densities of various shaped particles is found via a new
      proposed definition of the scaled aspect ratio. Finally, a rough linear
      relationship between the mean and standard deviation of the reduced Voronoi cell
      volumes is obtained only for the random packings. Our findings should lead to a
      better understanding toward the jammed and random packings and are helpful in
      guiding the granular material design.

PMID- 30218999
TI  - UV-induced transformations of matrix-isolated 6-azacytosine.
AB  - UV-induced transformations were studied for monomers of 6-azacytosine isolated in
      low-temperature Ar matrices. In contrast to cytosine, where the amino-hydroxy
      (AH) tautomer is the lowest-energy form, the amino-oxo (AO) and imino-oxo (IO)
      isomers of 6-azacytosine were found to be the most stable and most populated. Due
      to the high relative energy of the AH tautomer of 6-azacytosine, this form is not
      populated in low-temperature matrices after their formation and prior to any
      irradiation. Excitation of 6-azacytosine monomers with UV light from the 328-300
      nm range led to structural transformations of AO and IO forms. The initially most
      populated AO tautomer was observed either to convert, in a phototautomeric
      reaction, into the AH product or to undergo photodecarbonylation to yield 4-amino
      1,2,3-(2H)-triazole. The relative efficiencies of the two processes depend on the
      wavelength and on the pulsed or continuous-wave character of the UV light used
      for excitation. For the IO tautomer of 6-azacytosine, the excitation with UV 328
      300 nm light induced the photoconversion of the initially more populated anti IO1
      isomer into the syn IO2 form. This transformation was found to be partially
      photoreversible.

PMID- 30219000
TI  - Strong bonds and far-from-equilibrium conditions minimize errors in lattice-gas
      growth.
AB  - We use computer simulation to study the layer-by-layer growth of particle
      structures in a lattice gas, taking the number of incorporated vacancies as a
      measure of the quality of the grown structure. A dynamic scaling relation
      describes the quality of structures in and out of equilibrium and reveals that
      the highest-quality structures are obtained, for fixed observation time, using
      strong interactions and far-from-equilibrium growth conditions. This result
      contrasts with the usual assumption that weak interactions and mild
      nonequilibrium conditions are the best way to minimize errors during assembly.

PMID- 30219001
TI  - Erratum: "Dipolar Poisson-Boltzmann approach to ionic solutions: A mean field and
      loop expansion analysis" [J. Chem. Phys. 139, 164909 (2013)].

PMID- 30219002
TI  - Solvation of barium atoms and singly charged cations in acetonitrile clusters.
AB  - The size distributions of neutral and cationic Ba x (CH3CN) n (x = 0, +1; n <= 7)
      clusters, as produced by a standard laser vaporization-supersonic expansion pick
      up source, were determined from molecular beam experiments. The size distribution
      for cations is in the range of n = 1-7, whereas only the n = 1 complex is
      observed for neutral clusters, and these two features are unaffected by the
      variables controlling the performance of the cluster source. The distinct
      behavior is compatible with the expected charge-dipole interactions in the ionic
      species, which are stronger than the dipole induced-dipole interactions at play
      in neutral clusters, and it is corroborated by the relative magnitude of the
      theoretical successive binding energies (SBEs) for the lowest-lying isomers of
      cationic and neutral clusters with n = 1-5, as computed at the density functional
      theory level. The theoretical results also allow for the rationalization of the
      bimodal Ba+(CH3CN)1-7 size distribution, featuring an apparent minimum at n = 3,
      in terms of chiefly 6s-5d sigma hybridization of the Ba+ ions, which ultimately
      leads to a relatively small third SBE for the Ba+(CH3CN)3 complex, as compared to
      those for n = 1, 2, and 4. Additional Born-Oppenheimer molecular dynamics
      simulations on the Ba+(CH3CN)2-4 clusters suggest that all of the ligands are
      coordinated to the Ba+ ion and prevent considering completion of the first
      solvent shell as responsible for the bimodal size distribution.

PMID- 30219003
TI  - Quantum-induced solid-solid transitions and melting in the Lennard-Jones LJ38
      cluster.
AB  - The solid-solid and melting transitions that occur in Lennard-Jones LJ n clusters
      have been both fascinating and challenging for the computational physics
      community over the last several decades. A number of attempts to extend these
      studies to the quantum case have also been made. Particularly interesting is the
      exploration of the parallel between the thermally induced and quantum-induced
      transitions. Yet, both numerically accurate and systematic studies of the latter
      are still lacking. In this paper, we apply the diffusion Monte Carlo method to
      the especially difficult case of LJ38. Starting with the truncated octahedral
      global minimum configuration, as the de Boer quantum delocalization parameter
      Lambda increases, the system undergoes two consecutive solid-solid transitions,
      switching to anti-Mackay configurations. At sufficiently large values of Lambda,
      the cluster is completely "melted," which is manifested by delocalization of the
      ground state wavefunction over a very large number of minima that represent
      several structural motifs.

PMID- 30219004
TI  - A highly flexible molecule: The peculiar case of ethynyl isothiocyanate HCCNCS.
AB  - The rotational spectrum of the parent isotopic species of HCCNCS, along with
      those of three 13C singly substituted variants and one 34S minor isotopologue,
      has been observed with high resolution using Fourier transform microwave
      spectroscopy from 4 to 26 GHz. Based on the observed spectral pattern and
      assignment of the 14N nuclear quadrupole hyperfine structure, the geometry of
      HCCNCS is effectively linear, which is further supported by the observation of l 
      type doubling for rotational transitions in an excited bending state of the
      parent HCCNCS. The experimental observations are supported by high level quantum
      chemical calculations using the coupled-cluster singles and doubles model
      augmented by a perturbative correction for triple excitations, CCSD(T), level of
      theory that reveal an extremely shallow potential energy well along the CNC
      bending angle with a surprising basis set dependence.

PMID- 30219005
TI  - A new generation of effective core potentials from correlated calculations: 2nd
      row elements.
AB  - Very recently, we have introduced correlation consistent effective core
      potentials (ccECPs) derived from many-body approaches with the main target being
      their use in explicitly correlated methods, while still usable in mainstream
      approaches. The ccECPs are based on reproducing excitation energies for a subset
      of valence states, namely, achieving near-isospectrality between the original and
      pseudo Hamiltonians. In addition, binding curves of dimer molecules were used for
      refinement and overall improvement of transferability over a range of bond
      lengths. Here we apply similar ideas to the 2nd row elements and study several
      aspects of the constructions in order to find the high accuracy solutions within
      the chosen ccECP forms with 3s, 3p valence space (Ne-core). Our new constructions
      exhibit accurate low-lying atomic excitations and equilibrium molecular bonds (on
      average within ~0.03 eV and 3 mA); however, the errors for Al and Si oxide
      molecules at short bond lengths are notably larger for both ours and existing
      effective core potentials. Assuming this limitation, our ccECPs show a systematic
      balance between the criteria of atomic spectra accuracy and transferability for
      molecular bonds. In order to provide another option with much higher uniform
      accuracy, we also construct He-core ccECPs for the whole 2nd row with typical
      discrepancies of ~0.01 eV or smaller.

PMID- 30219006
TI  - Perspective: Accurate treatment of the quantum dynamics of light molecules inside
      fullerene cages: Translation-rotation states, spectroscopy, and symmetry
      breaking.
AB  - In this perspective, I review the current status of the theoretical
      investigations of the quantum translation-rotation (TR) dynamics and spectroscopy
      of light molecules encapsulated inside fullerenes, mostly C60 and C70. The
      methodologies developed in the past decade allow accurate quantum calculations of
      the TR eigenstates of one and two nanoconfined molecules and have led to deep
      insights into the nature of the underlying dynamics. Combining these bound-state
      methodologies with the formalism of inelastic neutron scattering (INS) has
      resulted in the novel and powerful approach for the quantum calculation of the
      INS spectra of a diatomic molecule in a nanocavity with an arbitrary geometry.
      These simulations have not only become indispensable for the interpretation and
      assignment of the experimental spectra but are also behind the surprising
      discovery of the INS selection rule for diatomics in near-spherical nanocavities.
      Promising directions for future research are discussed.

PMID- 30219007
TI  - Improving solvation energy predictions using the SMD solvation method and
      semiempirical electronic structure methods.
AB  - The PM6 implementation in the GAMESS program is extended to elements requiring d
      integrals and interfaced with the conducter-like polarized continuum model of
      solvation, including gradients. The accuracy of aqueous solvation energies
      computed using AM1, PM3, PM6, and DFT tight binding (DFTB) and the Solvation
      Model Density (SMD) continuum solvation model is tested using the Minnesota
      Solvation Database data set. The errors in SMD solvation energies predicted using
      Neglect of Diatomic Differential Overlap (NDDO)-based methods are considerably
      larger than when using density functional theory (DFT) and HF, with root mean
      square error (RMSE) values of 3.4-5.9 (neutrals) and 6-15 kcal/mol (ions)
      compared to 2.4 and ~5 kcal/mol for HF/6-31G(d). For the NDDO-based methods, the
      errors are especially large for cations and considerably higher than the
      corresponding conductor-like screening model results, which suggests that the
      NDDO/SMD results can be improved by re-parameterizing the SMD parameters focusing
      on ions. We found that the best results are obtained by changing only the radii
      for hydrogen, carbon, oxygen, nitrogen, and sulfur, and this leads to RMSE values
      for PM3 (neutrals: 2.8/ions: ~5 kcal/mol), PM6 (4.7/~5 kcal/mol), and DFTB
      (3.9/~5 kcal/mol) that are more comparable to HF/6-31G(d) (2.4/~5 kcal/mol).
      Although the radii are optimized to reproduce aqueous solvation energies, they
      also lead more accurate predictions for other polar solvents such as dimethyl
      sulfoxide, acetonitrile, and methanol, while the improvements for non-polar
      solvents are negligible.

PMID- 30219008
TI  - Stress correlations in glasses.
AB  - We rigorously establish that, in disordered three-dimensional isotropic solids,
      the stress autocorrelation function presents anisotropic terms that decay as 1/r3
      at long-range, with r being the distance, as soon as local stress fluctuations
      are normal, by which we mean that the fluctuations of stress, as averaged over
      spherical domains, decay as the inverse domain volume. Since this property is
      required for macroscopic stress to be self-averaging, it is expected to hold
      generically in all glasses and we thus conclude that the presence of 1/r3 stress
      correlation tails is the rule in these systems. Our proof follows from the
      observation that, in an infinite medium, when both material isotropy and
      mechanical balance hold, (i) the stress autocorrelation matrix is completely
      fixed by just two radial functions: the pressure autocorrelation and the trace of
      the autocorrelation of stress deviators; furthermore, these two functions (ii)
      fix the decay of the fluctuations of sphere-averaged pressure and deviatoric
      stresses with the increasing sphere volume. Our conclusion is reached because, in
      view of (ii), the normal decay of stress fluctuations is only compatible with
      both the pressure autocorrelation and the trace of the autocorrelation of stress
      deviators being integrable; in turn, due to the precise analytic relation (i)
      fixed by isotropy and mechanical balance, this condition demands the spatially
      anisotropic stress correlation terms to decay as 1/r3 at long-range.

PMID- 30219009
TI  - Eliminating spin-contamination of spin-flip time dependent density functional
      theory within linear response formalism by the use of zeroth-order mixed
      reference (MR) reduced density matrix.
AB  - The use of the mixed reference (MR) reduced density matrix, which combines
      reduced density matrices of the MS = +1 and -1 triplet-ground states, is proposed
      in the context of the collinear spin-flip-time-dependent density functional
      theory (SF-TDDFT) methodology. The time-dependent Kohn-Sham equation with the
      mixed state is solved by the use of spinor-like open-shell orbitals within the
      linear response formalism, which enables to generate additional configurations in
      the realm of TD-DFT. The resulting MR-SF-TDDFT computational scheme has several
      advantages before the conventional collinear SF-TDDFT. The spin-contamination of
      the response states of SF-TDDFT is nearly removed. This considerably simplifies
      the identification of the excited states, especially in the "black-box" type
      applications, such as the automatic geometry optimization, reaction path
      following, or molecular dynamics simulations. With the new methodology, the
      accuracy of the description of the excited states is improved as compared to the
      collinear SF-TDDFT. Several test examples, which include systems typified by
      strong non-dynamic correlation, orbital (near) degeneracy, and conical
      intersections, are given to illustrate the performance of the new method.

PMID- 30219010
TI  - NMR studies on the coupling of ion and water dynamics on various time and length
      scales in glass-forming LiCl aqueous solutions.
AB  - We combine 1H, 2H, and 7Li NMR methods to investigate the dynamics of water
      molecules and lithium ions in LiCl aqueous solutions over wide ranges of time and
      length scales down to their glass transitions. Structural relaxation times tau
      and self-diffusion coefficients D reveal that water and lithium dynamics are
      faster for lower salt content at ambient temperatures, while the differences
      vanish upon cooling when fractional freezing leads to similar salt concentrations
      in the remaining liquid phases. Relaxation times and diffusion coefficients of
      water molecules agree with those of lithium ions in the weakly supercooled
      regime, indicating that the dynamics are strongly coupled. Furthermore, non
      Arrhenius temperature dependence is found and the Stokes-Einstein relation is
      obeyed in this temperature range. However, we observe various decoupling
      phenomena for the motion of the constituents and for dynamics on different length
      scales in the deeply supercooled regime. Most notably, the rotational motion of
      the water molecules does not follow the glassy slowdown of the studied salt
      solutions below ~145 K, but it rather resembles that in nanoscopic confinement,
      molecular solutions, and high-density amorphous ice at low temperatures. This
      common low-temperature water dynamics is characterized by large-angle
      reorientation and Arrhenius temperature dependence.

PMID- 30219011
TI  - Ultrafast proton/deuteron dynamics in KTaO3 observed with infrared pump-probe
      spectroscopy: Toward understanding of proton conduction mechanism in solid
      oxides.
AB  - Infrared pump-probe measurement for the OD stretching mode in KTaO3 has been
      performed. We observed the induced absorption signal corresponding to the 1-2
      transition for the first time in oxide crystals in addition to the bleaching
      signal of the 0-1 transition. Both signals show long decay time of ~200 ps, and
      the potential anharmonicity is found to be 3.6%. We also investigated temperature
      dependence of OH/OD absorption spectra to explore how a proton/deuteron interacts
      with the surrounding lattice vibrations, and identify the phonon mode which
      causes the potential fluctuations as a O-Ta-O bending motion. On the basis of the
      results obtained, we calculate the potential energy surface on which a
      proton/deuteron moves and discuss the proton conduction mechanism in solid
      oxides.

PMID- 30219012
TI  - Vacuum ultraviolet photodissociation dynamics of N2O via the C1Pi state: The
      N(2Dj=5/2, 3/2) + NO(X2Pi) product channels.
AB  - We study the vacuum ultraviolet photodissociation dynamics of N2O via the C1Pi
      state by using the time-sliced velocity map ion imaging technique. Images of
      N(2Dj=5/2, 3/2) products from the N atom elimination channels were acquired at a
      set of photolysis wavelengths from 142.55 to 148.19 nm. Vibrational states of the
      NO(X2Pi) co-fragments were partially resolved in experimental images. From these
      images, the product total kinetic energy release distributions (TKERs), branching
      ratios of the vibrational states of NO(X2Pi) co-fragments, and the vibrational
      state specific angular anisotropy parameters (beta) have been determined. Notable
      features were found in the experimental results: the TKERs show that the NO(X2Pi)
      co-fragments are highly vibrationally excited. For the highly vibrationally
      excited state of NO(X2Pi), a bimodal rotational structure is found at all the
      studied photolysis wavelengths. Furthermore, the vibrational state specific beta
      values of both spin-orbit channels (j = 3/2, 5/2) clearly show a monotonic
      decrease as the vibrational quantum number of NO(X2Pi) increases. These
      observations suggest that multiple dissociation pathways play a role in the
      formation of the N(2Dj=5/2, 3/2) + NO(X2Pi) products: one corresponds to a fast
      dissociation pathway through the linear state (the C1Pi state) following the
      initial excitation to a slightly bent geometry in the vicinity of the linear C1Pi
      configuration, leading to the low rotationally excited components with relatively
      large beta values; the other corresponds to a relatively slow dissociation
      pathway through the bent C(31A') or C(31A") state, leading to moderately
      rotationally excited NO(X2Pi) products with smaller beta values.

PMID- 30219013
TI  - Automated assignment of rotational spectra using artificial neural networks.
AB  - A typical broadband rotational spectrum may contain several thousand observable
      transitions, spanning many species. While these spectra often encode troves of
      chemical information, identifying and assigning the individual spectra can be
      challenging. Traditional approaches typically involve visually identifying a
      pattern. A more modern approach is to apply an automated fitting routine. In this
      approach, combinations of 3 transitions are searched by trial and error, to fit
      the A, B, and C rotational constants in a Watson-type Hamiltonian. In this work,
      we develop an alternative approach-to utilize machine learning to train a
      computer to recognize the patterns inherent in rotational spectra. Broadband high
      resolution rotational spectra are perhaps uniquely suited for pattern
      recognition, assignment, and species identification using machine learning.
      Repeating patterns of transition frequencies and intensities are now routinely
      recorded in broadband chirped-pulse Fourier transform microwave experiments in
      which both the number of resolution elements and the dynamic range surpass 104.
      At the same time, these high-resolution spectra are extremely sensitive to
      molecular geometry with each polar species having a unique rotational spectrum.
      Here we train the feed forward neural network on thousands of rotational spectra
      that we calculate, using the rules of quantum mechanics, from randomly generated
      sets of rotational constants and other Hamiltonian parameters. Reasonable
      physical constraints are applied to these parameter sets, yet they need not
      belong to existing species. A trained neural network presented with a spectrum
      identifies its type (e.g., linear molecule, symmetric top, or asymmetric top) and
      infers the corresponding Hamiltonian parameters (rotational constants,
      distortion, and hyperfine constants). The classification and prediction times,
      about 160 us and 50 us, respectively, seem independent of the spectral complexity
      or the number of molecular parameters. We describe how the network works, provide
      benchmarking results, and discuss future directions.

PMID- 30219014
TI  - Photodetachment spectroscopy of cold trapped NH2- near threshold.
AB  - We have studied photodetachment of the amidogen anion NH2- as a function of
      photon energy near the detachment threshold. The detachment spectrum is obtained
      over the energy range of 6190-6355 cm-1 from the loss rate of the anions from a
      cryogenic radiofrequency multipole ion trap. By modeling all accessible
      rotational state-to-state photodetachment transitions, we can assign rotational
      state-specific thresholds to the measured spectrum. In this way, we have
      determined the electron affinity of NH2 to be 6224 +/- 1 cm-1.

PMID- 30219015
TI  - Dissociative electron attachment studies with hyperthermal Rydberg atoms.
AB  - Earlier studies of the velocity distributions of heavy-Rydberg ion-pair states
      formed in collisions between potassium Rydberg atoms with low-to-intermediate
      values of n, 10 ? n ? 15, and targets that attach free low-energy electrons have
      shown that such measurements can provide a window into the dynamics of
      dissociative electron capture. Here we propose that the reaction dynamics can be
      explored in much greater detail through studies using hyperthermal Rydberg atoms.
      This is demonstrated using, as an example, helium Rydberg atoms and a semi
      classical Monte Carlo collision code developed specifically to model the dynamics
      of Rydberg electron transfer in collisions between Rydberg atoms and attaching
      targets. The simulations show that the outcome of collisions is sensitive not
      only to the lifetime and decay energetics of the excited intermediate negative
      ion formed upon initial Rydberg electron capture but also to the radial electron
      probability density distribution in the Rydberg atom itself, i.e., to its l
      value.

PMID- 30219016
TI  - Vibrational exciton coupling in homo and hetero dimers of carboxylic acids
      studied by linear infrared and Raman jet spectroscopy.
AB  - The jet-cooled band positions of the C=O stretching vibrations in the three
      hetero dimers composed of formic, acetic, and pivalic acid have been determined.
      Resonance patterns in the symmetric stretching modes have been corrected for by
      assuming a single bright state. An analysis of their Davydov or vibrational
      exciton splitting shows that the hetero dimer values can be averaged from the
      respective homo dimer splittings (ranging from 56 cm-1 for the acetic to 75 cm-1
      for the formic acid dimer) with an error of <=7%. The set of 6 exciton splittings
      and 6 independent downshifts caused by double hydrogen bonding serves as a
      reference data base for the benchmarking of computational methods. B3LYP is shown
      to be unable to describe the difference between the formic and acetic acid
      monomer but is otherwise satisfactory, if one assumes that exciton splittings are
      only weakly affected by anharmonic effects beyond the deconvoluted local
      resonances. However, a vibrational perturbation theory test points at significant
      diagonal anharmonicity effects for the exciton splitting. Spin-component-scaled
      and canonical MP2 fail in reproducing experimental dimer shifts and splittings in
      the harmonic approximation, but anharmonic corrections are expected to improve
      the performance. Harmonic PBEh-3c reproduces the experimental data set well after
      scaling. The experimental data set the stage for more rigorous anharmonic
      treatments of the multidimensional coupling of C=O oscillators in carboxylic acid
      dimers and trimers. In addition, we report the first vibrational jet spectrum of
      cis-formic acid in the C=O stretching region by heating the nozzle and the nozzle
      feed line of the Raman setup.

PMID- 30219017
TI  - Upside/Downside statistical mechanics of nonequilibrium Brownian motion. II. Heat
      transfer and energy partitioning of a free particle.
AB  - The energy partitioning during activation and relaxation events under steady
      state conditions for a Brownian particle driven by multiple thermal reservoirs of
      different local temperatures is investigated. Specifically, we apply the
      formalism derived in Paper I [G. T. Craven and A. Nitzan, J. Chem. Phys. 148,
      044101 (2018)] to examine the thermal transport properties of two sub-ensembles
      of Brownian processes, distinguished at any given time by the specification that
      all the trajectories in each group have, at that time, energy either above
      (upside) or below (downside) a preselected energy threshold. Dynamical properties
      describing energy accumulation and release during activation/relaxation events
      and relations for upside/downside energy partitioning between thermal reservoirs
      are derived. The implications for heat transport induced by upside and downside
      events are discussed.

PMID- 30219018
TI  - Building maps in collective variable space.
AB  - Enhanced sampling techniques such as umbrella sampling and metadynamics are now
      routinely used to provide information on how the thermodynamic potential, or free
      energy, depends on a small number of collective variables (CVs). The free energy
      surfaces that one extracts by using these techniques provide a simplified or
      coarse-grained representation of the configurational ensemble. In this work, we
      discuss how auxiliary variables can be mapped in CV space. We show that maps of
      auxiliary variables allow one to analyze both the physics of the molecular system
      under investigation and the quality of the reduced representation of the system
      that is encoded in a set of CVs. We apply this approach to analyze the degeneracy
      of CVs and to compute entropy and enthalpy surfaces in CV space both for
      conformational transitions in alanine dipeptide and for phase transitions in
      carbon dioxide molecular crystals under pressure.

PMID- 30219019
TI  - Calculation of vibrational spectroscopic and geometrical characteristics of the
      [F(HF)2]- and [F(DF)2]- complexes using the second-order vibrational perturbation
      theory and a 6D variational method.
AB  - Vibrational spectroscopic and average geometrical parameters of the strong H
      bonded complexes [F(HF)2]- and [F(DF)2]- are determined for the first time from
      nine-dimensional (9D) perturbative and 6D variational calculations. The
      frequencies and intensities for all fundamental and some combination and overtone
      transitions obtained by the method of second-order vibrational perturbation
      theory (VPT2) are reported. A two-fold decrease in the H-F (D-F) stretching band
      frequency and a more than ten-fold increase in the intensity of this band upon
      complexation are predicted. The theoretical frequencies for both isolated
      isotopologues are in satisfactory agreement (to better than 70 cm-1) with the
      scarce experimental data obtained in condensed phases. The main purpose of
      variational calculations is to analyze the intermode anharmonic coupling and the
      changes in the geometrical parameters upon vibrational excitation and H/D
      isotopic substitution. The equilibrium nuclear configuration and the 2D potential
      energy surface (PES) of [F(HF)2]- for H-F stretches are calculated in the MP2/6
      311++G(3df,3pd), CCSD(T)/6-311++G(3df,3pd), CCSD(T)/aug-cc-pVTZ, and CCSD(T)/d
      aug-cc-pVTZ approximations with the basis set superposition error taken into
      account. Anharmonic vibrational problems are solved by the variational method for
      2D, 4D, and 6D systems of H-bond and H-F (D-F) stretches and in-plane bends. The
      VPT2 calculations and calculations of the PESs for 4D and 6D systems are
      performed in the MP2/6-311++G(3df,3pd) approximation. Comparison of variational
      anharmonic solutions for different vibrational subsystems demonstrates the
      influence of intermode anharmonic coupling on the mixing of wave functions and
      spectroscopic and geometrical characteristics. The inverse Ubbelohde effect is
      predicted and substantiated.

PMID- 30219020
TI  - Diabatic model for electrochemical hydrogen evolution based on constrained DFT
      configuration interaction.
AB  - The accuracy of density functional theory (DFT) based kinetic models for
      electrocatalysis is diminished by spurious electron delocalization effects, which
      manifest as uncertainties in the predicted values of reaction and activation
      energies. In this work, we present a constrained DFT (CDFT) approach to alleviate
      overdelocalization effects in the Volmer-Heyrovsky mechanism of the hydrogen
      evolution reaction (HER). This method is applied a posteriori to configurations
      sampled along a reaction path to correct their relative stabilities. Concretely,
      the first step of this approach involves describing the reaction in terms of a
      set of diabatic states that are constructed by imposing suitable density
      constraints on the system. Refined reaction energy profiles are then recovered by
      performing a configuration interaction (CDFT-CI) calculation within the basis
      spanned by the diabatic states. After a careful validation of the proposed
      method, we examined HER catalysis on open-ended carbon nanotubes and discovered
      that CDFT-CI increased activation energies and decreased reaction energies
      relative to DFT predictions. We believe that a similar approach could also be
      adopted to treat overdelocalization effects in other electrocatalytic proton
      coupled electron transfer reactions, e.g., in the oxygen reduction reaction.

PMID- 30219021
TI  - Relating Franck-Condon blockade to redox chemistry in the single-particle
      picture.
AB  - In this work, we explore Franck-Condon blockade in the "redox limit," where
      nuclear relaxation processes occur much faster than the rate of electron
      transfer. To this end, the quantized rate expressions for electron transfer are
      recast in terms of a quantized redox density of states (DOS) within a single
      phonon mode model. In the high temperature regime, this single-particle picture
      formulation of electron transfer is shown to agree well with the semi-classical
      rate and DOS expressions developed by Gerischer and Hopfield. Upon incorporation
      into a two electrode formulation, utilizing the master equation approach, the low
      temperature quantized conductance features of Franck-Condon blockade are
      reproduced. Moreover, at sufficiently large reorganization energies, it is argued
      that Franck-Condon blockade should also be observable in room temperature
      systems. In general, this work aims to further bridge descriptions of electron
      transfer and transport in the single-particle picture.

PMID- 30219023
TI  - On the memory kernel and the reduced system propagator.
AB  - We relate the memory kernel in the Nakajima-Zwanzig-Mori time-convolution
      approach to the reduced system propagator which is often used to obtain the
      kernel in the Tokuyama-Mori time-convolutionless approach. The connection
      provides a robust and simple formalism to compute the memory kernel for a
      generalized system-bath model circumventing the need to compute high order system
      bath observables, thus streamlining the use of numerically exact solvers for
      calculating the memory kernel. We illustrate this for a model system with
      electron-electron and electron-phonon couplings, driven away from equilibrium.

PMID- 30219024
TI  - Communication: A hybrid Bethe-Salpeter/time-dependent density-functional-theory
      approach for excitation energies.
AB  - A hybrid Bethe-Salpeter/time-dependent density-functional-theory method is
      described that aims at improving the performance of the GW/Bethe-Salpeter
      equation (GW/BSE) method in general and for excited triplet states in particular.
      The static screened exchange W used in the BSE is combined with the correlation
      kernel of the underlying density functional in a manner that retains a proven
      feature of the BSE, that is, the correct description of charge-transfer
      excitations. The performance of the new method, labeled cBSE, is assessed using
      G0W0 or evGW quasiparticle energies, and an improved performance is observed. The
      cBSE approach shows nearly equal performance for excited singlet and triplet
      states, rivaling coupled-cluster theory (in the CC2 approximation) in accuracy at
      a computational cost that is at least one order of magnitude smaller.

PMID- 30219022
TI  - Measuring the wall depletion length of nanoconfined DNA.
AB  - Efforts to study the polymer physics of DNA confined in nanochannels have been
      stymied by a lack of consensus regarding its wall depletion length. We have
      measured this quantity in 38 nm wide, square silicon dioxide nanochannels for
      five different ionic strengths between 15 mM and 75 mM. Experiments used the
      Bionano Genomics Irys platform for massively parallel data acquisition,
      attenuating the effect of the sequence-dependent persistence length and finite
      length effects by using nick-labeled E. coli genomic DNA with contour length
      separations of at least 30 um (88 325 base pairs) between nick pairs. Over 5 *
      106 measurements of the fractional extension were obtained from 39 291 labeled
      DNA molecules. Analyzing the stretching via Odijk's theory for a strongly
      confined wormlike chain yielded a linear relationship between the depletion
      length and the Debye length. This simple linear fit to the experimental data
      exhibits the same qualitative trend as previously defined analytical models for
      the depletion length but now quantitatively captures the experimental data.

PMID- 30219025
TI  - General theory of charge regulation and surface differential capacitance.
AB  - A generalization of the mean-field approach will be derived that will take into
      account the ion-ion as well as ion-surface non-electrostatic effects on an equal
      footing, being based on the bulk and surface equations of state in the absence of
      electrostatic interactions. This approach will be applied to the analysis of a
      single planar surface with dissociable sites with several models of the specific
      ion-surface non-electrostatic interactions, providing a general thermodynamic
      insight into the characteristics of the surface differential capacitance. The ion
      surface interactions and ion-ion packing considerations at the surface will be
      shown to be more relevant than the bulk packing constraints for ions vicinal to
      the surface, as well as to set in prior to the conditions where the bulk packing
      constraints would become relevant.

PMID- 30219026
TI  - Phage spanins: diversity, topological dynamics and gene convergence.
AB  - BACKGROUND: Spanins are phage lysis proteins required to disrupt the outer
      membrane. Phages employ either two-component spanins or unimolecular spanins in
      this final step of Gram-negative host lysis. Two-component spanins like Rz-Rz1
      from phage lambda consist of an integral inner membrane protein: i-spanin, and an
      outer membrane lipoprotein: o-spanin, that form a complex spanning the periplasm.
      Two-component spanins exist in three different genetic architectures; embedded,
      overlapped and separated. In contrast, the unimolecular spanins, like gp11 from
      phage T1, have an N-terminal lipoylation signal sequence and a C-terminal
      transmembrane domain to account for the topology requirements. Our proposed model
      for spanin function, for both spanin types, follows a common theme of the outer
      membrane getting fused with the inner membrane, effecting the release of progeny
      virions. RESULTS: Here we present a SpaninDataBase which consists of 528 two
      component spanins and 58 unimolecular spanins identified in this analysis.
      Primary analysis revealed significant differences in the secondary structure
      predictions for the periplasmic domains of the two-component and unimolecular
      spanin types, as well as within the three different genetic architectures of the
      two-component spanins. Using a threshold of 40% sequence identity over 40%
      sequence length, we were able to group the spanins into 143 i-spanin, 125 o
      spanin and 13 u-spanin families. More than 40% of these families from each type
      were singletons, underlining the extreme diversity of this class of lysis
      proteins. Multiple sequence alignments of periplasmic domains demonstrated
      conserved secondary structure patterns and domain organization within family
      members. Furthermore, analysis of families with members from different
      architecture allowed us to interpret the evolutionary dynamics of spanin gene
      arrangement. Also, the potential universal role of intermolecular disulfide bonds
      in two-component spanin function was substantiated through bioinformatic and
      genetic approaches. Additionally, a novel lipobox motif, AWAC, was identified and
      experimentally verified. CONCLUSIONS: The findings from this bioinformatic
      approach gave us instructive insights into spanin function, evolution, domain
      organization and provide a platform for future spanin annotation, as well as
      biochemical and genetic experiments. They also establish that spanins, like viral
      membrane fusion proteins, adopt different strategies to achieve fusion of the
      inner and outer membranes.

PMID- 30219027
TI  - Safety and efficacy of addition of hyaluronidase to a mixture of lidocaine and
      bupivacaine in scalp nerves block in elective craniotomy operations; comparative
      study.
AB  - BACKGROUND: Patients undergoing craniotomy operations are prone to various
      noxious stimuli, many strategies are commenced to provide state of analgesia, for
      better control of the stress response and to overcome its undesired effects on
      the haemodynamics and post-operative pain. Scalp nerves block are considered one
      of these strategies. This study was conceived to evaluate the effect of addition
      of hyaluronidase to the local anaesthetic mixture used in the scalp nerves block
      in patients undergoing elective craniotomy operations. METHODS: 64 patients
      undergoing elective craniotomy operations were enrolled in this prospective
      randomized, double-blind comparative study. Patients were randomly assigned to
      two groups. Group LA, patients subjected to scalp nerves block with 15 ml
      bupivacaine 0.5%, 15 ml lidocaine 2%, in 1:400000 epinephrine. Group H as Group
      LA with15 IU /ml Hyaluronidase. RESULTS: Patients in the H group showed lower VAS
      values for 8 h postoperative, compared to the LA group. The haemodynamic response
      showed lower values in the H group, compared to the LA group. Those effects were
      shown in the intraoperative period and for 6 h post-operative. No difference was
      detected regarding the incidence of complications nor the safety profile.
      CONCLUSION: Our data supports the idea that addition of hyaluronidase to the
      local anesthetic mixture improves the success rates of the scalp nerves block and
      its efficacy especially during stressful intraoperative periods and in the early
      postoperative period. No evident undesirable effects in relation to the addition
      of hyaluronidase. TRIAL REGISTRATION: Clinical Trial registry on
      ClinicalTrials.gov , NCT 03411330 , 25-1-2018.

PMID- 30219028
TI  - Vedolizumab use after failure of TNF-alpha antagonists in children and
      adolescents with inflammatory bowel disease.
AB  - BACKGROUND: Vedolizumab is safe and effective in adult patients with Crohn's
      disease (CD) and ulcerative colitis (UC); however, data in children with
      inflammatory bowel disease (IBD) are scarce. Therefore, we evaluated vedolizumab
      use in a cohort of Austrian paediatric patients with IBD. METHODS: Twelve
      patients (7 female; 7 CD; 5 UC), aged 8-17 years (median, 15 years), with severe
      IBD who received vedolizumab after tumour necrosis factor alpha antagonist
      treatment were retrospectively analysed. Clinical activity scores, relevant
      laboratory parameters, and auxological measures were obtained at infusion visits.
      RESULTS: In the CD group, 1/7 patient discontinued therapy due to a severe
      systemic allergic reaction; 1/7 and 2/7 patients achieved complete and partial
      response, respectively, at week 14; and 3/7 patients discontinued therapy due to
      a primary non-response or loss of response. In the UC group, complete clinical
      remission was achieved at weeks 2, 6, and 14 in 2/5, 1/5 and 1/5 patients
      respectively; partial response was observed in one patient at week 2. CD activity
      scores did not significantly change from baseline to week 38 (median 47.5 vs. 40
      points, p = 1,0), while median UC activity scores changed from 70 to 5 points (p
      < 0,001). Substantial weight gain and increased albumin and haemoglobin levels
      were observed in both groups. CONCLUSION: These results demonstrate that
      vedolizumab can be an effective treatment for individual paediatric patients with
      IBD who are unresponsive, intolerant, or experience a loss of efficacy in other
      therapies. However, vedolizumab appears to be more effective in paediatric UC
      than in paediatric CD.

PMID- 30219029
TI  - The Ottawa SAH search algorithms: protocol for a multi- centre validation study
      of primary subarachnoid hemorrhage prediction models using health administrative
      data (the SAHepi prediction study protocol).
AB  - BACKGROUND: Conducting prospective epidemiological studies of hospitalized
      patients with rare diseases like primary subarachnoid hemorrhage (pSAH) are
      difficult due to time and budgetary constraints. Routinely collected
      administrative data could remove these barriers. We derived and validated 3
      algorithms to identify hospitalized patients with a high probability of pSAH
      using administrative data. We aim to externally validate their performance in
      four hospitals across Canada. METHODS: Eligible patients include those >=18 years
      of age admitted to these centres from January 1, 2012 to December 31, 2013. We
      will include patients whose discharge abstracts contain predictive variables
      identified in the models (ICD-10-CA diagnostic codes I60** (subarachnoid
      hemorrhage), I61** (intracranial hemorrhage), 162** (other nontrauma intracranial
      hemorrhage), I67** (other cerebrovascular disease), S06** (intracranial injury),
      G97 (other postprocedural nervous system disorder) and CCI procedural codes 1JW51
      (occlusion of intracranial vessels), 1JE51 (carotid artery inclusion), 3JW10
      (intracranial vessel imaging), 3FY20 (CT scan (soft tissue of neck)), and 3OT20
      (CT scan (abdominal cavity)). The algorithms will be applied to each patient and
      the diagnosis confirmed via chart review. We will assess each model's
      sensitivity, specificity, negative and positive predictive value across the
      sites. DISCUSSION: Validating the Ottawa SAH Prediction Algorithms will provide a
      way to accurately identify large SAH cohorts, thereby furthering research and
      altering care.

PMID- 30219030
TI  - Selection at a genomic region of major effect is responsible for evolution of
      complex life histories in anadromous steelhead.
AB  - BACKGROUND: Disparity in the timing of biological events occurs across a variety
      of systems, yet the understanding of genetic basis underlying diverse phenologies
      remains limited. Variation in maturation timing occurs in steelhead trout, which
      has been associated with greb1L, an oestrogen target gene. Previous techniques
      that identified this gene only accounted for about 0.5-2.0% of the genome and
      solely investigated coastal populations, leaving uncertainty on the genetic basis
      of this trait and its prevalence across a larger geographic scale. RESULTS: We
      used a three-tiered approach to interrogate the genomic basis of complex
      phenology in anadromous steelhead. First, fine scale mapping with 5.3 million
      SNPs from resequencing data covering 68% of the genome confirmed a 309-kb region
      consisting of four genes on chromosome 28, including greb1L, to be the genomic
      region of major effect for maturation timing. Second, broad-scale
      characterization of candidate greb1L genotypes across 59 populations revealed
      unexpected patterns in maturation phenology for inland fish migrating long
      distances relative to those in coastal streams. Finally, genotypes from 890 PIT
      tag tracked steelhead determined associations with early versus late arrival to
      spawning grounds that were previously unknown. CONCLUSIONS: This study clarifies
      the genetic bases for disparity in phenology observed in steelhead, determining
      an unanticipated trait association with premature versus mature arrival to
      spawning grounds and identifying multiple candidate genes potentially
      contributing to this variation from a single genomic region of major effect. This
      illustrates how dense genome mapping and detailed phenotypic characterization can
      clarify genotype to phenotype associations across geographic ranges of species.

PMID- 30219031
TI  - Questionnaire results on exposure characteristics of pregnant women participating
      in the Japan Environment and Children Study (JECS).
AB  - BACKGROUND: The Japan Environment and Children's Study (JECS) is a nation-wide
      birth cohort study investigating environmental effects on children's health and
      development. In this study, the exposure characteristics of the JECS
      participating mothers were summarized using two questionnaires administered
      during pregnancy. METHODS: Women were recruited during the early period of their
      pregnancy. We intended to administer the questionnaire during the first trimester
      (MT1) and the second/third trimester (MT2). The total number of registered
      pregnancies was 103,099. RESULTS: The response rates of the MT1 and MT2
      questionnaires were 96.8% and 95.1%, respectively. The mean gestational ages
      (SDs) at the time of the MT1 and MT2 questionnaire responses were 16.4 (8.0) and
      27.9 (6.5) weeks, respectively. The frequency of participants who reported
      "lifting something weighing more than 20 kg" during pregnancy was 5.3% for MT1
      and 3.9% for MT2. The Cohen kappa scores ranged from 0.07 to 0.54 (median 0.31)
      about the occupational chemical use between MT1 and MT2 questionnaires. Most of
      the participants (80%) lived in either wooden detached houses or steel-frame
      collective housing. More than half of the questionnaire respondents answered that
      they had "mold growing somewhere in the house". Insect repellents and
      insecticides were used widely in households: about 60% used "moth repellent for
      clothes in the closet," whereas 32% applied "spray insecticide indoors" or
      "mosquito coil or an electric mosquito repellent mat." CONCLUSIONS: We summarized
      the exposure characteristics of the JECS participants using two maternal
      questionnaires during pregnancy.

PMID- 30219032
TI  - Promoting safe walking among older people: the effects of a physical and
      cognitive training intervention vs. physical training alone on mobility and falls
      among older community-dwelling men and women (the PASSWORD study): design and
      methods of a randomized controlled trial.
AB  - BACKGROUND: Safe and stable walking is a complex process involving the
      interaction of neuromuscular, sensory and cognitive functions. As physical and
      cognitive functions deteriorate with ageing, training of both functions may have
      more beneficial effects on walking and falls prevention than either alone. This
      article describes the study design, recruitment strategies and interventions of
      the PASSWORD study investigating whether a combination of physical and cognitive
      training (PTCT) has greater effects on walking speed, dual-task cost in walking
      speed, fall incidence and executive functions compared to physical training (PT)
      alone among 70-85-year-old community-dwelling sedentary or at most moderately
      physically active men and women. METHODS: Community-dwelling sedentary or at most
      moderately physically active, men and women living in the city of Jyvaskyla will
      be recruited and randomized into physical training (PT) and physical and
      cognitive training (PTCT). The 12-month interventions include supervised training
      sessions and home exercises. Both groups attend physical training intervention,
      which follows the current physical activity guidelines. The PTCT group performes
      also a web-based computer program targeting executive functions. Outcomes will be
      assessed at baseline and at 6 and 12 months thereafter. Falls data are collected
      during the interventions and the subsequent one-year follow-up. The primary
      outcome is 10-m walking speed. Secondary outcomes include 6-min walking distance,
      dual-task cost in walking speed, fall incidence and executive function assessed
      with color Stroop and Trail Making A and B tests. Explanatory outcomes include
      e.g. body composition and bone characteristics, physical performance, physical
      activity, life-space mobility, fall-related self-efficacy, emotional well-being
      and personality characteristics. DISCUSSION: The study is designed to capture the
      additive and possible synergistic effects of physical and cognitive training.
      When completed, the study will provide new knowledge on the effects of physical
      and cognitive training on the prevention of walking limitations and rate of falls
      in older people. The expected results will be of value in informing strategies
      designed to promote safe walking among older people and may have a significant
      health and socio-economic impact. TRIAL REGISTRATION: ISRCTN52388040 .

PMID- 30219033
TI  - A cross-sectional study of the relationship between sexual compulsivity and
      unprotected anal intercourse among men who have sex with men in shanghai, China.
AB  - BACKGROUND: HIV prevalence among men who have sex with men (MSM) in China is
      rising rapidly, and unprotected anal intercourse (UAI) is associated with HIV
      transmission. Recent research has shown that associations between UAI and other
      factors can differ according to the type of sex partners, including regular
      partners and casual partners. This study aimed to explore the relationship
      between sexual compulsivity and UAI according to partner type among MSM in
      Shanghai, China. METHODS: A cross-sectional study was conducted among 547 MSM
      from four districts in Shanghai, China. All participants were recruited using
      snowball sampling. The Sexual Compulsivity Scale was used to evaluate
      participants' sexual compulsivity. Multivariable logistic regression was used to
      identify factors associated with sexual compulsivity and UAI. The mediation
      effects of substance use before sex on the relationship between sexual
      compulsivity and UAI were tested through mediation analyses. RESULTS: After
      adjusting for sociodemographic variables, sexual compulsivity was associated with
      overall UAI (adjusted odds ratios [AOR] = 1.039, 95% confidence intervals [CI] =
      1.004-1.075), UAI with non-regular sex partners (AOR = 1.089, 95% CI = 1.033
      1.148) and UAI with commercial sex partners (AOR = 1.185, 95% CI = 1.042-1.349).
      No significant association was found between sexual compulsivity and UAI with
      regular sex partners (AOR = 1.029, 95% CI = 0.984-1.077). Mediation analyses
      indicated that the relationship between sexual compulsivity and UAI was not
      mediated by either alcohol use before sex or drug use before sex. CONCLUSIONS:
      The association between sexual compulsivity and UAI varies depending on the type
      of UAI partner. Therefore, individuals may engage in different types of UAI for
      different reasons, and tailored HIV cognitive-behavioral intervention programs
      are needed.

PMID- 30219034
TI  - Interventions to address social connectedness and loneliness for older adults: a
      scoping review.
AB  - BACKGROUND: Older adults are at risk for loneliness, and interventions to promote
      social connectedness are needed to directly address this problem. The nature of
      interventions aimed to affect the distinct, subjective concepts of
      loneliness/social connectedness has not been clearly described. The purpose of
      this review was to map the literature on interventions and strategies to affect
      loneliness/social connectedness for older adults. METHODS: A comprehensive
      scoping review was conducted. Six electronic databases were searched from
      inception in July 2015, resulting in 5530 unique records. Standardized
      inclusion/exclusion criteria were applied, resulting in a set of 44 studies
      (reported in 54 articles) for further analysis. Data were extracted to describe
      the interventions and strategies, and the context of the included studies.
      Analytic techniques included calculating frequencies, manifest content analysis
      and meta-summary. RESULTS: Interventions were described or evaluated in 39
      studies, and five studies described strategies to affect loneliness/social
      connectedness of older adults or their caregivers in a qualitative descriptive
      study. The studies were often conducted in the United States (38.6%) among
      community dwelling (54.5%), cognitively intact (31.8%), and female-majority
      (86.4%) samples. Few focused on non-white participants (4.5%). Strategies
      described most often were engaging in purposeful activity and maintaining contact
      with one's social network. Of nine intervention types identified, the most
      frequently described were One-to-One Personal Contact and Group Activity. Authors
      held divergent views of why the same type of intervention might impact social
      connectedness, but social contact was the most frequently conceptualized
      influencing factor targeted, both within and across intervention types.
      CONCLUSIONS: Research to test the divergent theories of why interventions work is
      needed to advance understanding of intervention mechanisms. Innovative
      conceptualizations of intervention targets are needed, such as purposeful
      activity, that move beyond the current focus on the objective social network as a
      way to promote social connectedness for older adults.

PMID- 30219035
TI  - TUSC2P suppresses the tumor function of esophageal squamous cell carcinoma by
      regulating TUSC2 expression and correlates with disease prognosis.
AB  - BACKGROUND: Pseudogenes are RNA transcripts with high homology with its parent
      protein-coding genes. Although pseudogenes lost the ability to produce protein,
      it still exert import biological function, and play important role in the
      pathogenesis of a wide varity of tumors; However, the role of pseudogenes in
      esophageal squamous cell carcinoma (ESCC) is poorly understood. METHODS: TUSC2P
      function in ESCC were explored using both in vitro and in vivo experiments cell
      proliferation, invasion and apoptosis assay was performed to evaluated the effect
      of TUSC2P on the tumor biology of ESCC. Expression of relative genes was assessed
      by quantitative real-time PCR (qRT-PCR) and western blotting in EC109 and TE-1
      cell, as well as ESCC patients. 3'UTR luciferase assay was used to confirm the
      direct binding of miRNAs with TUSC2 and TUSC2P 3'UTR. Relation betweenTUSC2P,
      TUSC2 and ESCC prognosis was predicted by survival analysis (n = 56). RESULTS:
      Pseudogene TUSC2P was down regulated in ESCC tissues compared with paired normal
      adjacent tissues, and the expression of TUSC2P was significantly correlated with
      survivalof ESCC patients. Over expression of TUSC2P in EC109 and TE-1 cells
      resulted in altered expression of TUSC2, thus inhibited proliferation, invasion
      and promoted apoptosis. Dual luciferase assay demonstrated that TUSC2P 3'UTR
      decoyed miR-17-5p, miR-520a-3p, miR-608, miR-661 from binding to TUSC2.
      CONCLUSIONS: TUSC2P can suppresses the tumor function of esophageal squamous cell
      carcinoma by regulating TUSC2 expression and may also serve as a prognostic
      factor for ESCC patients.

PMID- 30219036
TI  - Technology-based cognitive training and rehabilitation interventions for
      individuals with mild cognitive impairment: a systematic review.
AB  - BACKGROUND: Individuals with mild cognitive impairment (MCI) are at heightened
      risk of developing dementia. Rapid advances in computing technology have enabled
      researchers to conduct cognitive training and rehabilitation interventions with
      the assistance of technology. This systematic review aims to evaluate the effects
      of technology-based cognitive training or rehabilitation interventions to improve
      cognitive function among individuals with MCI. METHODS: We conducted a systematic
      review using the following criteria: individuals with MCI, empirical studies, and
      evaluated a technology-based cognitive training or rehabilitation intervention.
      Twenty-six articles met the criteria. RESULTS: Studies were characterized by
      considerable variation in study design, intervention content, and technologies
      applied. The major types of technologies applied included computerized software,
      tablets, gaming consoles, and virtual reality. Use of technology to adjust the
      difficulties of tasks based on participants' performance was an important
      feature. Technology-based cognitive training and rehabilitation interventions had
      significant effect on global cognitive function in 8 out of 22 studies; 8 out of
      18 studies found positive effects on attention, 9 out of 16 studies on executive
      function, and 16 out of 19 studies on memory. Some cognitive interventions
      improved non-cognitive symptoms such as anxiety, depression, and ADLs.
      CONCLUSION: Technology-based cognitive training and rehabilitation interventions
      show promise, but the findings were inconsistent due to the variations in study
      design. Future studies should consider using more consistent methodologies.
      Appropriate control groups should be designed to understand the additional
      benefits of cognitive training and rehabilitation delivered with the assistance
      of technology.

PMID- 30219037
TI  - Differential expression of miRNA-146a and miRNA-155 in gastritis induced by
      Helicobacter pylori infection in paediatric patients, adults, and an animal
      model.
AB  - BACKGROUND: Helicobacter pylori is a major aetiologic agent associated with
      gastritis. H. pylori infections increase the expression of the Toll-like receptor
      (TLR), which in turn modulates the expression of microRNA (miRNA)-146a and miRNA
      155. The objective of this study was to compare the expression of miRNA-146a and
      miRNA-155 in gastric lesions of paediatric and adult patients with different
      pathologies and in Mongolian gerbils (Meriones unguiculatus) infected with H.
      pylori 26,695. METHODS: Quantification of miRNA expression was performed by
      quantitative real-time polymerase chain reaction (qRT-PCR) of paraffin-embedded
      gastric lesions of children with or without an infection (n = 25), adults with
      follicular gastritis and metaplasia (n = 32) and eight-week-old M. unguiculatus
      males (Hsd:MON) infected with H. pylori 26,695 for 0, 3, 6, 12 and 18 months (n =
      25). The genes RNU48 and RNU6 were used as endogenous controls for data
      normalization. Statistical analyses were performed using Kruskal-Wallis, Mann
      Whitney, ANOVA and Student's t-test. RESULTS: The expression of miRNA-146a and
      miRNA-155 in infected children increased by 247.6- and 79.4-fold (on average),
      respectively, compared to that observed in the control group. However, these
      results were not significant (p = 0.12 and p = 0.07 respectively). In some
      children a gradual increase in expression was observed, while in others,
      expression was very high. Additionally, the expression levels of miRNA-146a and
      miRNA-155 increased by an average of 21.7- and 62-fold, respectively, in adult
      patients with follicular gastritis when compared to those of the controls. In M.
      unguiculatus infected with H. pylori 26,695, the expression of both miRNAs
      increased as the infection progressed. CONCLUSION: This is the first report to
      show differences in the expression of miRNA-146a and miRNA-155 in paediatric and
      adult patients with gastritis who were infected with H. pylori. In addition, in
      M. unguiculatus infected with H. pylori, miRNA expression was associated with the
      progression of infection and the ability of the bacteria to adapt to the host.

PMID- 30219038
TI  - "That's probably what my mama's lungs look like": how adolescent children react
      to pictorial warnings on their parents' cigarette packs.
AB  - BACKGROUND: Pictorial cigarette pack warnings discourage smoking, but most
      evidence comes from studies of adults. Our qualitative study explored
      adolescents' reactions to pictorial warnings on their parents' cigarette packs.
      METHODS: We interviewed 24 adolescents whose parents received pictorial warnings
      on their cigarette packs as part of a randomized clinical trial. We conducted a
      thematic content analysis of the interview transcripts. RESULTS: Pictorial
      cigarette pack warnings led adolescents to imagine the depicted health effects
      happening to their parents, which elicited negative emotions. The warnings
      inspired adolescents to initiate conversations with their parents and others
      about quitting smoking. Adolescents believed the warnings would help smokers quit
      and prevent youth from starting smoking. Some current smokers said the warnings
      made them consider quitting. CONCLUSIONS: Conversations about the pictorial
      warnings may amplify their effectiveness for smokers, their adolescent children,
      and friends of the adolescent children. Cigarette pack warnings may reach a broad
      audience that includes adolescent children of smokers.

PMID- 30219039
TI  - Phenotypic and functional heterogeneity of peripheral gammadelta T cells in
      pulmonary TB and HIV patients in Addis Ababa, Ethiopia.
AB  - BACKGROUND: Previous studies reported HIV infection alters the distribution and
      function of gammadelta T cells and their subsets. gammadelta T phenotypes in
      healthy and diseased individuals has received little attention in Ethiopia. We
      conducted this study to analyze the distribution of gammadelta T cells, the
      subsets and levels of expression of activation (CD38), exhaustion or anergy
      (CD95, PD1), adhesion (N-CAM/CD56 and CD103), among HIV and TB infected patients.
      METHOD: The distributions of total gammadelta T cells, Vdelta1 and Vdelta2 T
      cells subsets were analyzed in clinical samples collected from asymptomatic HIV,
      pulmonary TB patients and apparently healthy controls. Multicolor flow cytometry
      and IFN-gamma ELISA were used to assess surface markers and functional responses
      of Vdelta2 T cells to isopentenyl pyrophosphate stimulation, respectively.
      RESULT: A total of 52 study participants were enrolled in this study, 22 HIV + TB
      , 10 HIV-TB+ and 20 healthy controls. No significant differences were observed in
      the distribution of total gammadelta T cells and in the proportion of Vdelta1
      subsets in all study groups, though slightly higher proportions were observed in
      HIV + TB- patients for the latter, of borderline statistical significance (p =
      0.07). However, the proportion of Vdelta2 T cells, as well as the IFN-gamma
      response to IPP stimulation, was significantly reduced in HIV + TB- patients
      compared to healthy controls (p < 0.002). Expression of the activation marker
      CD38 (p < 0.001) and adhesion marker CD103 (alphaEbeta7) were significantly
      higher in the Vdelta1 T cell subset among both HIV + TB- (p = 0.013) and HIV-TB+
      (p = 0.006) patients compared to healthy controls. Similarly, exhaustion markers,
      CD95 and PD1, were significantly higher in these two T cell subsets among both
      HIV + TB- and HIV-TB+ patients (p < 0.01). Interestingly, we also observed an
      increased proportion of effector memory (CD45RA-CD27-) and effector cytotoxic
      (CD45RA + CD27-) Vdelta2 T cell subsets in HIV negative pulmonary TB patients.
      CONCLUSION: In sum, HIV infection was associated with an increase in Vdelta1 and
      a decrease in the function and frequencies of Vdelta2 T cells. Moreover,
      increased effector Vdelta2 T cells were observed among HIV negative pulmonary TB
      patients suggesting a potential role of these T cells in the host response to TB.

PMID- 30219040
TI  - Early cost-effectiveness of tumor infiltrating lymphocytes (TIL) for second line
      treatment in advanced melanoma: a model-based economic evaluation.
AB  - BACKGROUND: An emerging immunotherapy is infusion of tumor infiltrating
      Lymphocytes (TIL), with objective response rates of around 50% versus 19% for
      ipilimumab. As an Advanced Therapeutic Medicinal Products (ATMP), TIL is highly
      personalized and complex therapy. It requests substantial upfront investments
      from the hospital in: expensive lab-equipment, staff expertise and training, as
      well as extremely tight hospital logistics. Therefore, an early health economic
      modelling study, as part of a Coverage with Evidence Development (CED) program,
      was performed. METHODS: We used a Markov decision model to estimate the expected
      costs and outcomes (quality-adjusted life years; QALYs) for TIL versus ipilimumab
      for second line treatment in metastatic melanoma patients from a Dutch health
      care perspective over a life long time horizon. Three mutually exclusive health
      states (stable disease (responders)), progressive disease and death) were
      modelled. To inform further research prioritization, Value of Information (VOI)
      analysis was performed. RESULTS: TIL is expected to generate more QALYs compared
      to ipilimumab (0.45 versus 0.38 respectively) at lower incremental cost
      (presently ?81,140 versus ?94,705 respectively) resulting in a dominant ICER
      (less costly and more effective). Based on current information TIL is dominating
      ipilimumab and has a probability of 86% for being cost effective at a cost/QALY
      threshold of ?80,000. The Expected Value of Perfect Information (EVPI) amounted
      to ?3 M. CONCLUSIONS: TIL is expected to have the highest probability of being
      cost-effective in second line treatment for advanced melanoma compared to
      ipilimumab. To reduce decision uncertainty, a clinical trial investigating e.g.
      costs and survival seems most valuable. This is currently being undertaken as
      part of a CED program in the Netherlands Cancer Institute, Amsterdam, the
      Netherlands, in collaboration with Denmark.

PMID- 30219042
TI  - The association between muscular strength and depression in Korean adults: a
      cross-sectional analysis of the sixth Korea National Health and Nutrition
      Examination Survey (KNHANES VI) 2014.
AB  - BACKGROUND: There are conflicting researches on the relationship between muscular
      strength and depression, the most common mental illness. There is no study of
      relationship between muscular strength and depression using national data from
      young adults to seniors. For example, there has not been a study done explaining
      mediating pathways among the influences of handgrip strength on depression. Here,
      we conducted survey for the association between relative handgrip strength and
      depression and explain mediated pathways for quality of life. METHODS: A cross
      sectional study was administered to 4298 Korean adult subjects, aged 19-80 years,
      based on the 6th Korean National Health and Nutrition Examination Survey (KNHANES
      VI) of 2014. Handgrip strength reported as the average with each hand. The
      relative handgrip strength is defined as the handgrip strength divided by the
      body mass index (BMI). We performed analysis for all subjects and age groups
      (young adult, middle-aged, and elderly). We analyzed the association using
      multivariate linear regression and logistic regression. We also conducted
      mediation analysis for quality of life, which was measured by the EuroQol Five
      Dimension Questionnaire (EQ5D). RESULTS: After adjusting for covariates, handgrip
      strength was inversely associated with the PHQ-9 score (P < 0.05). The odds
      ratios (OR) of depression symptoms were statistically significant for
      participants in the first and second quartile of handgrip strength compared to
      those with the highest quartile in entire sample, young adult, middle-aged, and
      elderly. There was about a 50% mediation effect of EQ5D in the relationship
      between handgrip strength and depression. CONCLUSIONS: Using a large national
      sample, our results found that lower handgrip strength is associated with an
      increased risk of depression in Korean adult (young adult, middle-aged, and
      elderly). Our results suggest that increasing muscular strength may prevent
      depression in Korean adults.

PMID- 30219041
TI  - Risk factors for prehypertension and their interactive effect: a cross- sectional
      survey in China.
AB  - BACKGROUND: Individuals with prehypertension are at higher risk of developing
      hypertension and cardiovascular diseases, while the interaction between factors
      may aggravate prehypertension risk. Therefore, this study aimed to evaluate the
      risk factors for prehypertension in Chinese middle-aged and elderly adults, and
      explore the potentially interactive effect of evaluated factors. METHODS: All the
      participants that came from a community based cross-sectional survey were
      investigated in Bengbu, China, by being interviewed with a questionnaire. Body
      mass index (BMI), Waist circumference (WC) and lipid accumulation product (LAP)
      that reflect participants' obesity were also calculated. In addition, logistic
      regression model was applied to explore the risk factors of prehypertension,
      followed by the assessment of the interactive effects between risk factors on
      prehypertension by the relative excess risk due to interaction (RERI),
      attributable proportion due to interaction (AP) and synergy index (SI). RESULTS:
      A total of 1777 participants were enrolled in this study, among which the
      prevalence of normtension, prehypertension and hypertension were 41.70%, 33.93%
      and 24.37% respectively. According to the multivariate logistic regression
      analysis, age (OR: 1.01, 95%CI: 1.00-1.02), smoking (OR: 1.67, 95%CI: 1.22-2.29),
      family history of cardiovascular diseases (OR: 1.52, 95%CI: 1.14-2.02), general
      obesity (OR: 1.51, 95%CI: 1.15-1.97) and LAP (OR: 2.58, 95%CI: 1.76-3.80) were
      all defined as the major factors that significantly related with the risk of
      prehypertension. When identifying prehypertension risk, the receiver-operating
      characteristics (ROC) curves (AUC) analysis indicated that LAP performed better
      than BMI in males (Z = 2.05, P = 0.03) and females (Z = 2.12, P = 0.03), but was
      superior to WC only in females (Z = 2.43, P = 0.01). What is more, there were
      significant interactive effects of LAP with family history of cardiovascular
      diseases (RERI: 1.88, 95%CI: 0.25-3.51; AP: 0.44, 95%CI: 0.20-0.69; SI: 2.37,
      95%CI: 1.22-4.60) and smoking (RERI: 1.99, 95%CI: 0.04-3.93; AP: 0.42, 95%CI:
      0.17-0.67; SI: 2.16, 95%CI: 1.68-4.00) on prehypertension risk. The value of AP
      (0.40, 95%CI: 0.03-0.77) also indicated a significant interaction between family
      history of cardiovascular diseases and smoking on prehypertension. CONCLUSION:
      Prehypertension is currently prevalent in Chinese adults. This study indicated
      that age, family history of cardiovascular diseases, smoking, general obesity and
      LAP were significantly related with prehypertension risk. Furthermore,
      interactive effects on risk of prehypertension had been demonstrated in this
      study as well, which would help researchers to build strategy against
      prehypertension more comprehensively and scientifically.

PMID- 30219044
TI  - The paediatric version of Wisconsin gait scale, adaptation for children with
      hemiplegic cerebral palsy: a prospective observational study.
AB  - BACKGROUND: In clinical practice there is a need for a specific scale enabling
      detailed and multifactorial assessment of gait in children with spastic
      hemiplegic cerebral palsy. The practical value of the present study is linked
      with the attempts to find a new, affordable, easy-to-use tool for gait assessment
      in children with spastic hemiplegic cerebral palsy. The objective of the study is
      to evaluate the Wisconsin Gait Scale (WGS) in terms of its inter- and intra-rater
      reliability in observational assessment of walking in children with hemiplegic
      cerebral palsy. METHODS: The study was conducted in a group of 34 patients with
      hemiplegic cerebral palsy. At the first stage, the original version of the
      ordinal WGS was used. The WGS, consisting of four subscales, evaluates fourteen
      gait parameters which can be observed during consecutive gait phases. At the
      second stage, a modification was introduced in the kinematics description of the
      knee and weight shift, in relation to the original scale. The same video
      recordings were rescored using the new, paediatric version of the WGS. Three
      independent examiners performed the assessment twice. Inter and intra-observer
      reliability of the modified WGS were determined. RESULTS: The findings show very
      high inter- and intra-observer reliability of the modified WGS. This was
      reflected by a lack of systematically oriented differences between the repeated
      measurements, very high value of Spearman's rank correlation coefficient 0.9 <=
      |R| < 1, very high value of ICC > 0.9, and low value of CV < 2.5% for the
      specific physical therapists. CONCLUSIONS: The new, ordinal, paediatric version
      of WGS, proposed by the authors, seems to be useful as an additional tool that
      can be used in qualitative observational gait assessment of children with spastic
      hemiplegic cerebral palsy. Practical dimension of the study lies in the fact that
      it proposes a simple, easy-to-use tool for a global gait assessment in children
      with spastic hemiplegic cerebral palsy. However, further research is needed to
      validate the modified WGS by comparing it to other observational scales and
      objective 3-dimensional spatiotemporal and kinematic gait parameters. TRIAL
      REGISTRATION: anzctr.org.au , ID: ACTRN12617000436370 . Registered 24 March 2017.

PMID- 30219043
TI  - Impact of reduced exposure to calcineurin inhibitors on the development of de
      novo DSA: a cohort of non-immunized first kidney graft recipients between 2007
      and 2014.
AB  - BACKGROUND: In low-immunological risk kidney transplant recipients (KTRs),
      reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive
      for avoiding adverse events, but may increase the risk of developing de novo
      Donor Specific Antibodies (dnDSA). METHODS: CNI exposure was retrospectively
      analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels
      (C0) collected during follow-up. Reduced exposure to CNI was defined as follows:
      C0 less than the lower limit of the international targets for >=50% of follow-up.
      RESULTS: During a mean follow-up of 5.0 +/- 2.0 years, 39 patients (15.8%)
      developed dnDSA (MFI >=1000). Patients with DSA were significantly younger (46.6
      +/- 13.8 vs. 51.7 +/- 14.0 years, p = 0.039), received more frequently poorly
      matched grafts (59% with 6-8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and
      had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002).
      Reduced exposure to CNI was associated with an increased risk of dnDSA
      (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on
      patient survival, graft loss from any cause including death, or post-transplant
      cancer. CONCLUSIONS: Even in a low-immunological risk population, reduced
      exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of
      under-immunosuppression must be carefully evaluated before deciding on CNI
      minimization.

PMID- 30219045
TI  - Polymorphisms in the H19 gene and the risk of lung Cancer among female never
      smokers in Shenyang, China.
AB  - BACKGROUND: Long non-coding RNA (lncRNA) H19 is a hot spot in tumor development,
      progression and metastasis. This study assessed the association between H19
      genetic polymorphisms and the susceptibility of lung cancer. METHODS: The case
      control study was conducted to evaluate the association between four selected
      single nucleotide polymorphisms (rs217727, rs2107425, rs2735469 and rs17658052)
      in H19 gene and the risk of lung cancer. There were 556 female never smoking lung
      cancer patients and 395 cancer-free controls. Unconditional logistic regression
      analysis was used to analyze the associations between four SNPs and lung cancer
      risks by calculating the odds ratios and their 95% confidence intervals. The gene
      environment interactions were assessed on both additive and multiplicative
      scales. RESULTS: Compared with carriers carrying homozygous CC genotype, there
      was a statistically significant increased risk of lung cancer for carriers of the
      rs2107425 TT genotype (odds ratio = 1.599, 95%CI = 1.106-2.313, P = 0.013). In
      both dominant and recessive models, significant associations were found between
      rs2107425 and lung cancer risk, and the corresponding odds ratios were 1.346
      (1.022-1.774) and 1.400 (1.011-1.937), with P values 0.035 and 0.043,
      respectively. There was no significant correlation between lung cancer risk and
      rs2735469, rs217727 and rs17658052. Interaction analysis showed that their
      combined effects had a greater impact on lung cancer than individual effects of
      polymorphism and cooking smoke exposure. However, further analysis showed that
      the both additive model and the multiplicative model were not statistically
      significant. CONCLUSION: The polymorphism rs2107425 in H19 gene was associated
      with the risk of lung cancer among female who never smokes in Shenyang, China.

PMID- 30219046
TI  - First evidence of maternally inherited mosaicism in TGFBR1 and subtle primary
      myocardial changes in Loeys-Dietz syndrome: a case report.
AB  - BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder
      characterized by vascular and skeletal abnormalities, with considerable intra-
      and interfamilial variability. CASE PRESENTATION: We report the case of an 8-year
      old male with clinical features of two distinct genetic disorders, namely LDS,
      manifesting in the first months by progressive aortic root dilatation, arterial
      tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA)
      manifesting by white hair and skin that does not tan, nystagmus, reduced iris
      pigment with iris translucency, and reduced retinal pigment). We identified
      previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and
      heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family
      history revealed that his mother underwent multiple surgical repairs for
      recurrent hemorrhage originating from the buccal artery. Molecular studies
      confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18%
      in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells).
      Maternal cardiac investigations revealed peculiar cardiovascular features: mild
      tortuosity at the aortic arch, dilatation of the proximal abdominal aorta,
      multiple deep left ventricular myocardial crypts, and dysplastic mitral valve.
      TGFBR2 germline mosaicism has been described in three fathers of children
      carrying TGFBR2 mutations but, to the best of our knowledge, no case of
      maternally inherited TGFBR1 mutation mosaicism has been reported so far.
      CONCLUSIONS: This case report suggests that individuals with somatic mosaicism
      might be at risk for mild and unusual forms of LDS but germline mosaicism can
      lead to full blown picture of the disease in offspring.

PMID- 30219047
TI  - Lower mortality after early supervised pulmonary rehabilitation following COPD
      exacerbations: a systematic review and meta-analysis.
AB  - BACKGROUND: Pulmonary rehabilitation (PR), delivered as a supervised
      multidisciplinary program including exercise training, is one of the cornerstones
      in the chronic obstructive pulmonary disease (COPD) management. We performed a
      systematic review and meta-analysis to assess the effect on mortality of a
      supervised early PR program, initiated during or within 4 weeks after
      hospitalization with an acute exacerbation of COPD compared with usual post
      exacerbation care or no PR program. Secondary outcomes were days in hospital,
      COPD related readmissions, health-related quality of life (HRQoL), exercise
      capacity (walking distance), activities of daily living (ADL), fall risk and drop
      out rate. METHODS: We identified randomized trials through a systematic search
      using MEDLINE, EMBASE and Cocharne Library and other sources through October
      2017. Risk of bias was assessed regarding randomization, allocation sequence
      concealment, blinding, incomplete outcome data, selective outcome reporting, and
      other biases using the Cochrane Risk of Bias tool. RESULTS: We included 13
      randomized trials (801 participants). Our meta-analyses showed a clinically
      relevant reduction in mortality after early PR (4 trials, 319 patients; RR = 0.58
      (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients;
      RR = 0.55 (95% CI: [0.12 to 2.57])). Early PR reduced number of days in hospital
      by 4.27 days (1 trial, 180 patients; 95% CI: [- 6.85 to - 1.69]) and hospital
      readmissions (6 trials, 319 patients; RR = 0.47 (95% CI: [0.29 to 0.75])).
      Moreover, early PR improved HRQoL and walking distance, and did not affect drop
      out rate. Several of the trials had unclear risk of bias in regard to the
      randomization and blinding, for some outcome there was also a lack of power.
      CONCLUSION: Moderate quality of evidence showed reductions in mortality, number
      of days in hospital and number of readmissions after early PR in patients
      hospitalized with a COPD exacerbation. Long-term effects on mortality were not
      statistically significant, but improvements in HRQoL and exercise capacity
      appeared to be maintained for at least 12 months. Therefore, we recommend early
      supervised PR to patients with COPD-related exacerbations. PR should be initiated
      during hospital admission or within 4 weeks after hospital discharge.

PMID- 30219048
TI  - Accurate flexible refinement of atomic models against medium-resolution cryo-EM
      maps using damped dynamics.
AB  - BACKGROUND: Dramatic progress has recently been made in cryo-electron microscopy
      technologies, which now make possible the reconstruction of a growing number of
      biomolecular structures to near-atomic resolution. However, the need persists for
      fitting and refinement approaches that address those cases that require modeling
      assistance. METHODS: In this paper, we describe algorithms to optimize the
      performance of such medium-resolution refinement methods. These algorithms aim to
      automatically optimize the parameters that define the density shape of the
      flexibly fitted model, as well as the time-dependent damper cutoff distance.
      Atomic distance constraints can be prescribed for cases where extra containment
      of parts of the structure is helpful, such as in regions where the density map is
      poorly defined. Also, we propose a simple stopping criterion that estimates the
      probable onset of overfitting during the simulation. RESULTS: The new set of
      algorithms produce more accurate fitting and refinement results, and yield a
      faster rate of convergence of the trajectory toward the fitted conformation. The
      latter is also more reliable due to the overfitting warning provided to the user.
      CONCLUSIONS: The algorithms described here were implemented in the new Damped
      Dynamics Flexible Fitting simulation tool "DDforge" in the Situs package.

PMID- 30219049
TI  - Continued increases in blood pressure over two decades in Samoa (1991-2013);
      around one-third of the increase explained by rising obesity levels.
AB  - BACKGROUND: To analyse trends over the period 1991-2013 in systolic blood
      pressure (SBP), diastolic blood pressure (DBP) and the prevalence of hypertension
      in adults aged 25-64 years in Samoa; and to assess the contribution of rising
      obesity levels to period trends. METHODS: Unit record data from seven population
      based surveys (n = 10,881) conducted between 1991 and 2013 were included for
      analysis. Surveys were adjusted to the nearest previous census to improve
      national representativeness. Hypertension was defined as SBP >=140 mmHg and/or
      DBP >=90 mmHg and/or on medication for hypertension. Obesity was measured by body
      mass index (BMI). Poisson, linear and meta-regression were used to assess period
      trends. RESULTS: Over 1991-2013 mean SBP and DBP (mmHg), and the prevalence of
      hypertension (%) increased in both sexes. Increases in hypertension were: from
      18.3 to 33.9% (p < 0.001) in men (mean BP from 122/74 to 132/78); and from 14.3
      to 26.4% (p < 0.001) in women (mean BP from 118/73 to 126/78). The estimate of
      the age-adjusted mean SBP and DBP over 1991-2013, and the relative risk for
      hypertension in 2013 compared to 1991, were attenuated after adjusting for BMI:
      by 22% (men) and 32% (women) for mean SBP; 37% (men) and 32% (women) for mean
      DBP; and 19% in both sexes for hypertension. CONCLUSIONS: Significant increases
      have occurred in SBP/DBP and hypertension prevalence in both sexes in Samoa
      during 1991-2013, which would contribute significantly to premature mortality
      from cardiovascular disease. Obesity accounts for around one-third of the rising
      trend in blood pressure in the Samoan population. Strengthening of population
      control of hypertension through reduction in obesity and salt intake, and case
      detection and treatment through primary care, is required to reduce premature
      mortality from cardiovascular disease in Samoa.

PMID- 30219050
TI  - The role of nutrition, intimate partner violence and social support in prenatal
      depressive symptoms in rural Ethiopia: community based birth cohort study.
AB  - BACKGROUND: Depression during pregnancy has far-reaching adverse consequences on
      mothers, children and the whole family. The magnitude and determinants of
      prenatal depressive symptoms in low-resource countries are not well established.
      This study aims to describe the prevalence of prenatal depressive symptoms and
      whether it is associated with maternal nutrition, intimate partner violence and
      social support among pregnant women in rural Ethiopia. METHODS: This study is
      based on the baseline data from a large prospective, community-based, birth
      cohort study conducted in the South Western part of Ethiopia from March 2014 to
      March 2016. A total of 4680 pregnant women were recruited between 12 and 32 weeks
      of gestation. Depressed mood was assessed using the Patient Health Questionnaire
      (PHQ-9) scale and a cut off of >=8 was taken to define prenatal depressive
      symptoms. Data collection was conducted electronically on handheld tablets and
      submitted to a secured server via an internet connection. Bivariate and
      multivariate logistic regression analyses were computed using IBM SPSS version 20
      software. RESULT: The community based prevalence of depressive symptoms during
      pregnancy was 10.8% (95%Confidence Interval (CI): 9.92-11.70). Adjusting for
      confounding variables, moderate household food insecurity (OR 1.74; 95% CI: 1.31
      2.32), severe household food insecurity (OR 7.90; 95% CI: 5.87-10.62), anaemia
      (OR = 1.30; 95% CI: 1.04-1.61) and intimate partner violence (OR 3.08; 95% CI:
      2.23-4.25) were significantly associated with prenatal depressive symptoms. On
      the other hand, good social support from friends, families and husband reduced
      the risk of prenatal depressive symptoms by 39% (OR 0.61; 95% CI: 0.50-0.76).
      CONCLUSION: Prenatal depressive symptomatology is rather common during pregnancy
      in rural Ethiopia. In this community based study, household food insecurity,
      anaemia and intimate partner violence were significantly associated with prenatal
      depressive symptoms. Good maternal social support from friends, families and
      spouse was rather protective. The study highlights the need for targeted
      screening for depression and intimate partner violence during pregnancy. Policies
      aimed at reducing household food insecurity, maternal anaemia and intimate
      partner violence during pregnancy may possibly reduce depression.

PMID- 30219051
TI  - Prognostic value of early, conventional proton magnetic resonance spectroscopy in
      cooled asphyxiated infants.
AB  - BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) commonly leads to
      neurodevelopmental impairment, raising the need for prognostic tools which may
      guide future therapies in time. Prognostic value of proton MR spectroscopy (H
      MRS) between 1 and 46 days of age has been extensively studied; however, the
      reproducibility and generalizability of these methods are controversial in a
      general clinical setting. Therefore, we investigated the prognostic performance
      of conventional H-MRS during first 96 postnatal hours in hypothermia-treated
      asphyxiated neonates. METHODS: Fifty-one consecutive hypothermia-treated HIE
      neonates were examined by H-MRS at three echo-times (TE = 35, 144, 288 ms)
      between 6 and 96 h of age, depending on clinical stability. Patients were divided
      into favorable (n = 35) and unfavorable (n = 16) outcome groups based on
      psychomotor and mental developmental index (PDI and MDI, Bayley Scales of Infant
      Development II) scores (>= 70 versus < 70 or death, respectively), assessed at 18
      26 months of age. Associations between 36 routinely measured metabolite ratios
      and outcome were studied. Age-dependency of metabolite ratios in whole patient
      population was assessed. Prognostic performance of metabolite ratios was
      evaluated by Receiver Operating Characteristics (ROC) analysis. RESULTS: Three
      metabolite ratios showed significant difference between outcome groups after
      correction for multiple testing (p < 0.0014): myo-inositol (mIns)/N-acetyl
      aspartate (NAA) height, mIns/creatine (Cr) height, both at TE = 35 ms, and NAA/Cr
      height at TE = 144 ms. Assessment of age-dependency showed that all 3 metabolite
      ratios (mIns/NAA, NAA/Cr and mIns/Cr) stayed constant during first 96 postnatal
      hours, rendering them optimal for prediction. ROC analysis revealed that mIns/NAA
      gives better prediction for outcome than NAA/Cr and mIns/Cr with cut-off values
      0.6798 0.6274 and 0.7798, respectively, (AUC 0.9084, 0.8396 and 0.8462,
      respectively, p < 0.00001); mIns/NAA had the highest specificity (95.24%) and
      sensitivity (84.62%) for predicting outcome of neonates with HIE any time during
      the first 96 postnatal hours. CONCLUSIONS: Our findings suggest that during first
      96 h of age even conventional H-MRS could be a useful prognostic tool in
      predicting the outcome of asphyxiated neonates; mIns/NAA was found to be the best
      and age-independent predictor.

PMID- 30219053
TI  - Up-regulated expression of E2F2 is necessary for p16INK4a-induced cartilage
      injury.
AB  - BACKGROUND: Cartilage degradation would result in osteoarthritis (OA).
      p16INK4awas found in some age-related diseases. In this study, we aimed to
      determine the role of p16INK4a during OA and to investigate the underlying
      mechanisms. METHODS: Enzyme-linked immunosorbent assay (ELISA) was performed to
      test the activity of senescence-associated secretory phenotype (SASP). Real-time
      PCR (RT-PCR) and Western blot were used to determine the expressions of target
      genes. RESULTS: The increased expressions of p16INK4a and E2F2 were accompanied
      with cartilage degradation induced by IL-1beta. Over-expression of p16INK4a
      enhanced the secretion of SASP markers (TGFbeta, IL-6, IL-8, IL-1alpha, MMP3 and
      MMP13), reduced the expression of type II procollagen (COL2A1).Thus, the over
      expression of p16INK4a lead to cartilage injury. Moreover, we found that the
      expression of E2F2 was enhanced in p16INK4a over-expression group, and that
      cartilage injury caused by p16INK4a was alleviated by depleting E2F2.
      CONCLUSIONS: p16INK4a was up-regulated during the cartilage injury in OA.
      p16INK4a promoted cartilage injury by increasing the expression of E2F2. Thus,
      this study extends the molecular regulation network for understanding
      pathological progression of OA, and provides potential therapeutic target for OA.

PMID- 30219052
TI  - Effects of alternate day calorie restriction and exercise on cardio-metabolic
      risk factors in overweight and obese adults: an exploratory randomized controlled
      study.
AB  - BACKGROUND: It has been recognized that alternate day calorie restriction (ADCR)
      or exercise has positive effects on cardio-metabolic risk factors. It is unclear
      whether the combined effect of ADCR and exercise (aerobic + resistance training)
      influences risk. We investigated effects of an 8-week ADCR and exercise program
      (aerobic + resistance training) on cardio-metabolic risk factors in overweight
      and obese adults. METHODS: This study randomized 45 overweight or obese but
      healthy adults (F = 26, M = 19; aged about 32 to 40 years) into 4 groups: ADCR (n
      = 13), exercise (n = 10), exercise plus ADCR (n = 12), and control (n = 10) for 8
      weeks. Body composition, blood lipids profile, and insulin resistance were
      measured. The intention to treat (ITT) method was used to analyze all
      participants that were randomized. RESULTS: A total of 35 participants completed
      the trial (78%). Body weight, body mass index, waist circumference, fat mass and
      percent body fat were reduced in the exercise plus ADCR group (- 3.3 +/- 2.4 kg,
      p < 0.01; - 1.3 +/- 1.0 kg/m2, p < 0.01; - 4.1 +/- 3.9 cm, p < 0.01; - 2.7 +/-
      2.0 kg, p < 0.01; - 2. 5 +/- 2.2%, p < 0.01). Insulin, glucose, homeostasis model
      assessment insulin resistance and triglyceride (- 2.9 +/- 4.1 MUIU/ml, p < 0.05; 
      10.9 +/- 16.9 mg/dl, p < 0.05; - 0.9 +/- 1.3, p < 0.05; - 43.8 +/- 41.9 mg/dl, p
      < 0.01) decreased in the exercise plus ADCR group only. CONCLUSIONS: ADCR and
      exercise both proved to be beneficial, but the combined intervention was most
      effective at inducing beneficial changes in body weight, body composition,
      glucose, insulin, insulin resistance and triglyceride in overweight and obese
      adults. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03652532 , Registered August
      28, 2018, 'retrospectively registered'.

PMID- 30219054
TI  - A pilot study on adjunctive use of parametric colour-coded digital subtraction
      angiography in endovascular interventions of haemodialysis access.
AB  - BACKGROUND: Two-dimensional digital subtraction angiography (DSA) is the gold
      standard for angiographic evaluation of dysfunctional haemodialysis access. We
      aim to investigate the utility of parametric colour coded DSA in providing
      hemodynamic analysis during haemodialysis access interventions. METHODS: We
      retrospectively studied 20 patients who underwent access intervention and applied
      parametric colour-coding on selected DSA acquisitions before and after
      percutaneous transluminal angioplasty (PTA). The difference in time to peak
      (dTTP) contrast enhancement and time attenuation curve (TAC) of pre- and post
      stenotic regions of interest (ROIs) were obtained and compared after treatment.
      RESULTS: Improvements were seen in mean percent of stenosis after PTA (p <
      0.0001) for all cases. Median dTTP improved from 0.52 (IQR 0.26, 0.8) to 0.25
      (IQR 0, 0.26) seconds (p = 0.001). Median 50% contrast washout time improved from
      0.77 (IQR 0.39, 1.17) to 0.42 (IQR 0.23, 0.59) seconds (p = 0.031). Significant
      correlation was seen for dTTP vs. percent of stenosis (r = 0.723, p = 0.043) pre
      PTA and for change in dTTP vs. percent change in stenosis post-PTA (r = 0.786, p
      = 0.021) for inflow lesions. Such correlation was however not seen in outflow
      lesions. CONCLUSIONS: Adjunctive use of parametric colour-coded DSA may provide
      potentially useful hemodynamic information during vascular access interventions.
      Larger prospective studies are needed to validate our findings.

PMID- 30219055
TI  - Small RNA and degradome sequencing used to elucidate the basis of tolerance to
      salinity and alkalinity in wheat.
AB  - BACKGROUND: Soil salinity and/or alkalinity impose a major constraint over crop
      yield and quality. An understanding of the molecular basis of the plant response
      to these stresses could inform the breeding of more tolerant varieties. The bread
      wheat cultivar SR3 exhibits an enhanced level of salinity tolerance, while SR4 is
      distinguished by its superior tolerance of alkalinity. RESULTS: The small RNA and
      degradome sequencing was used to explore the miRNAs and corresponding targets
      associated with the superior stress tolerance of the SR lines. An examination of
      the small RNA content of these two closely related lines revealed the presence of
      98 known and 219 novel miRNA sequences. Degradome libraries were constructed in
      order to identify the targets of the miRNAs, leading to the identification of 58
      genes targeted by 26 of the known miRNAs and 549 targeted by 65 of the novel
      ones. The function of two of the stress-responsive miRNAs was explored using
      virus-induced gene silencing. CONCLUSIONS: This analysis indicated that
      regulation mediated by both auxin and epigenetic modification can be important in
      determining both salinity and alkalinity tolerance, while jasmonate signaling and
      carbohydrate metabolism are important for salinity tolerance, as is proton
      transport for alkalinity tolerance.

PMID- 30219056
TI  - Antimicrobial resistance of pathogens causing nosocomial bloodstream infection in
      Hubei Province, China, from 2014 to 2016: a multicenter retrospective study.
AB  - BACKGROUND: Data on the pathogens responsible for nosocomial bloodstream
      infection (BSI) and their antimicrobial resistance (AMR) in Hubei province are
      limited. This study was conducted to determine the major pathogens causing BSI
      and to characterize their AMR. METHODS: Data from the China Antimicrobial
      Resistance Surveillance System (CARSS) from 2014 to 2016 were analyzed
      retrospectively. RESULTS: Escherichia coli, Staphylococcus aureus and Klebsiella
      pneumoniae were the most common pathogens responsible for nosocomial BSI.
      Individuals aged 0-5 years and >= 40 years old were the major demographics at
      risk of infection by E. coli, K. pneumoniae, Pseudomonas aeruginosa,
      Acinetobacter baumannii and Enterobacter cloacae, while individuals aged 0-5
      years were the major demographic at risk of infection by S. aureus, Enterococcus
      faecalis, E. faecium, Streptococcus pneumoniae and Stenotrophomonas maltophilia.
      The frequencies of E. coli and K. pneumoniae isolates resistant to cefotaxime
      were 59.1% and 24.3%, respectively, and the frequencies of resistant isolates to
      ceftazidime were 42.9% and 27.2%, respectively. From 2014 to 2016, the frequency
      of extended-spectrum beta-lactamase (ESBL)-positive E. coli declined from 29.07
      to 24.5%, and the frequency of ESBL-positive K. pneumoniae declined from 18.64 to
      12.33%. The frequency of carbapenem-resistant (CR) E. coli was below 0.5%, but 1
      10% of K. pneumoniae isolates were CR. CONCLUSIONS: The emergence of methicillin
      resistant S. aureus and the expansion of ESBL and fluoroquinolone resistance
      among Gram-negative Enterobacteriaceae increased AMR severity. Carbapenemase
      producing K. pneumoniae isolates responsible for nosocomial BSI increased year
      over year and effective infection control measures should be taken to prevent
      them from spreading.

PMID- 30219057
TI  - The knowledge and perceptions of the first year medical students of an
      International University on family planning and emergency contraception in
      Nicosia (TRNC).
AB  - BACKGROUND: Informing the individuals on family planning including emergency
      contraception is a significant step for preventing unintended pregnancies.
      Although there is a number of studies on family planning and emergency
      contraception globally and in Turkey, no such data are available in the Turkish
      Republic of Northern Cyprus. The objective of this study was to evaluate the
      knowledge and perceptions on family planning and emergency contraception of the
      first year students of an international medical school in Nicosia, Northern
      Cyprus and to increase awareness for developing new policies on the issue.
      METHODS: The data of this cross-sectional study were collected in February 2016
      by a questionnaire of 36 questions. Of the 229 students, 189 (82.5%) completed
      the questionnaire. The data were evaluated by SPSS 18.0 statistical program. The
      differences of variables were evaluated by Chi square test, p < 0.05 being
      accepted as significant. RESULTS: The distribution of participants from 23
      countries according to nationality revealed three leading countries: Nigeria,
      Turkey and Syria. Of the students, 53.6% knew the definition of family planning.
      The sources of information were mainly school, the internet and media, with a
      total of 60.9% of the participants who stated having prior information on the
      subject. Awareness of contraceptive methods was indicated by more than 90% and
      emergency contraception by 66.1% of the participants. However, the students were
      unable to differentiate between modern and traditional family planning methods;
      85.6% did not have knowledge of the most effective period for emergency
      contraception and 63.1%, of the definition of emergency contraceptive pills.
      CONCLUSIONS: In conclusion, the knowledge and awareness level of the first year
      medical students on family planning and emergency contraception was insufficient.
      Family planning and emergency contraception education should be provided for the
      students at the first year of all faculties as well as medical schools and
      relevant programs should be included in the curricula of medical education.

PMID- 30219058
TI  - Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial
      cell function in ex vivo murine and human lung tissue cultures of pulmonary
      fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung
      disease. Repetitive injury and reprogramming of the lung epithelium are thought
      to be critical drivers of disease progression, contributing to fibroblast
      activation, extracellular matrix remodeling, and subsequently loss of lung
      architecture and function. To date, Pirfenidone and Nintedanib are the only
      approved drugs known to decelerate disease progression, however, if and how these
      drugs affect lung epithelial cell function, remains largely unexplored. METHODS:
      We treated murine and human 3D ex vivo lung tissue cultures (3D-LTCs; generated
      from precision cut lung slices (PCLS)) as well as primary murine alveolar
      epithelial type II (pmATII) cells with Pirfenidone or Nintedanib. Murine 3D-LTCs
      or pmATII cells were derived from the bleomycin model of fibrosis. Early fibrotic
      changes were induced in human 3D-LTCs by a mixture of profibrotic factors.
      Epithelial and mesenchymal cell function was determined by qPCR, Western
      blotting, Immunofluorescent staining, and ELISA. RESULTS: Low MUM concentrations
      of Nintedanib (1 MUM) and mM concentrations of Pirfenidone (2.5 mM) reduced
      fibrotic gene expression including Collagen 1a1 and Fibronectin in murine and
      human 3D-LTCs as well as pmATII cells. Notably, Nintedanib stabilized expression
      of distal lung epithelial cell markers, especially Surfactant Protein C in pmATII
      cells as well as in murine and human 3D-LTCs. CONCLUSIONS: Pirfenidone and
      Nintedanib exhibit distinct effects on murine and human epithelial cells, which
      might contribute to their anti-fibrotic action. Human 3D-LTCs represent a
      valuable tool to assess anti-fibrotic mechanisms of potential drugs for the
      treatment of IPF patients.

PMID- 30219059
TI  - Impact of nanoparticle surface functionalization on the protein corona and
      cellular adhesion, uptake and transport.
AB  - BACKGROUND: Upon ingestion, nanoparticles can interact with the intestinal
      epithelial barrier potentially resulting in systemic uptake of nanoparticles.
      Nanoparticle properties have been described to influence the protein corona
      formation and subsequent cellular adhesion, uptake and transport. Here, we aimed
      to study the effects of nanoparticle size and surface chemistry on the protein
      corona formation and subsequent cellular adhesion, uptake and transport. Caco-2
      intestinal cells, were exposed to negatively charged polystyrene nanoparticles
      (PSNPs) (50 and 200 nm), functionalized with sulfone or carboxyl groups, at nine
      nominal concentrations (15-250 MUg/ml) for 10 up to 120 min. The protein coronas
      were analysed by LC-MS/MS. RESULTS: Subtle differences in the protein composition
      of the two PSNPs with different surface chemistry were noted. High-content
      imaging analysis demonstrated that sulfone PSNPs were associated with the cells
      to a significantly higher extent than the other PSNPs. The apparent cellular
      adhesion and uptake of 200 nm PSNPs was not significantly increased compared to
      50 nm PSNPs with the same surface charge and chemistry. Surface chemistry
      outweighs the impact of size on the observed PSNP cellular associations. Also
      transport of the sulfone PSNPs through the monolayer of cells was significantly
      higher than that of carboxyl PSNPs. CONCLUSIONS: The results suggest that the
      composition of the protein corona and the PSNP surface chemistry influences
      cellular adhesion, uptake and monolayer transport, which might be predictive of
      the intestinal transport potency of NPs.

PMID- 30219060
TI  - BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas
      gingivalis-Streptococcus gordonii biofilms.
AB  - BACKGROUND: Porphyromonas gingivalis adherence to oral streptococci is a key
      point in the pathogenesis of periodontal diseases (Honda in Cell Host Microbe
      10:423-425, 2011). Previous work in our groups has shown that a region of the
      streptococcal antigen denoted BAR (SspB Adherence Region) inhibits P.
      gingivalis/S. gordonii interaction and biofilm formation both in vitro and in a
      mouse model of periodontitis (Daep et al. in Infect Immun 74:5756-5762, 2006;
      Daep et al. in Infect immun 76:3273-3280, 2008; Daep et al. in Infect Immun 79:67
      74, 2011). However, high localized concentration and prolonged exposure are
      needed for BAR to be an effective therapeutic in the oral cavity. METHODS: To
      address these challenges, we fabricated poly(lactic-co-glycolic acid) (PLGA) and
      methoxy-polyethylene glycol PLGA (mPEG-PLGA) nanoparticles (NPs) that encapsulate
      BAR peptide, and assessed the potency of BAR-encapsulated NPs to inhibit and
      disrupt in vitro two-species biofilms. In addition, the kinetics of BAR
      encapsulated NPs were compared after different durations of exposure in a two
      species biofilm model, against previously evaluated BAR-modified NPs and free
      BAR. RESULTS: BAR-encapsulated PLGA and mPEG-PLGA NPs potently inhibited biofilm
      formation (IC50 = 0.7 MUM) and also disrupted established biofilms (IC50 = 1.3
      MUM) in a dose-dependent manner. In addition, BAR released during the first 2 h
      of administration potently inhibits biofilm formation, while a longer duration of
      3 h is required to disrupt pre-existing biofilms. CONCLUSIONS: These results
      suggest that BAR-encapsulated NPs provide a potent platform to inhibit (prevent)
      and disrupt (treat) P. gingivalis/S. gordonii biofilms, relative to free BAR.

PMID- 30219061
TI  - Multimorbidity and health-related quality of life in Koreans aged 50 or older
      using KNHANES 2013-2014.
AB  - BACKGROUND: Multimorbidity negatively affects health outcomes and impairs health
      related quality of life (HRQoL). We assessed the prevalence of multimorbidity in
      Koreans aged 50 and older, taking into consideration their socioeconomic status,
      and estimated the loss in HRQoL due to multimorbidity. METHODS: This study is
      based on an analysis of data for adults aged 50 and older derived from the cross
      sectional nationally representative Korean National Health and Nutrition
      Examination Survey conducted in 2013-14. The five most prevalent chronic diseases
      and disease dyads were identified. The impact of the degree of multimorbidity,
      sex, and socioeconomic status on the European Quality of Life 5 Dimension (EQ-5D)
      index score were analyzed. Marital status, educational attainment, household
      income, basic livelihood security benefit, and occupation were considered as
      socioeconomic factors. RESULTS: The analysis included 5996 adults aged 50 years
      and older with males comprising 46.6%. Two or more chronic diseases were present
      in 26.8% of the participants aged 50 and older and 37.9% of the participants aged
      65 and older. The most prevalent dyadic combination was hypertension and
      dyslipidemia in the 50 and older group, and hypertension and osteoarthritis in
      the 65 and older age group. Hypertension dominated the multimorbidity
      combinations (four of the five most prevalent multimorbidity dyads), while a few
      conditions such as osteoarthritis had a relatively large influence on quality of
      life. In addition to the degree of multimorbidity, female and lower socioeconomic
      status were associated with significantly lower EQ-5D index scores. CONCLUSIONS:
      Integrated, holistic healthcare based on a patient-oriented perspective for
      earlier, more effective intervention, targeting multimorbidity is warranted.
      Special consideration should be given to patients with low socioeconomic status.

PMID- 30219062
TI  - Efficacy of high zinc biofortified wheat in improvement of micronutrient status,
      and prevention of morbidity among preschool children and women - a double masked,
      randomized, controlled trial.
AB  - BACKGROUND: Biofortification of staple food crops with zinc (Zn) can be one of
      the cost-effective and sustainable strategies to combat zinc deficiency and
      prevent morbidity among the target population. Agronomic approaches such as
      application of Zn fertilizers to soil and/or foliar spray seem to be a practical
      tool for Zn biofortification of wheat. However, there is a need to evaluate its
      efficacy from randomized controlled trials. This study aimed to evaluate the
      efficacy of zinc biofortified wheat flour on zinc status and its impact on
      morbidity among children aged 4-6 years and non-pregnant non lactating woman of
      child bearing age (WCBA) in Delhi, India. METHODS: In a community based, double
      masked randomized controlled trial, 6005 participants (WCBA and child pairs) were
      enrolled and randomly allocated to receive either high zinc biofortified wheat
      flour (HZn, 30 ppm zinc daily) or low zinc biofortified wheat flour (LZn, 20 ppm
      zinc daily) for 6 months (WCBA @ 360 g/day and children @ 120 g/day). Baseline
      and endline blood samples were obtained for assessing hematological markers; zinc
      status and data on compliance and morbidity were collected. RESULTS: Compliance
      rates were high; ~ 88% of the WCBAs in both the groups consumed 50% or more of
      recommended amount of biofortfied wheat flour during the follow up. Similarly
      86.9% children in HZn and 87.5% in LZn consumed 50% or more of recommended wheat
      flour intake. There was no significant difference in mean zinc levels between the
      groups at end study. This observation might be due to a marginal difference in
      zinc content (10 ppm) between the HZn and LZn wheat flour, and a short
      intervention period. However a positive impact of bio-fortification on self
      reported morbidity was observed. Compared to children in LZn group, children in
      HZn group had 17% (95% CI: 6 to 31%, p = 0.05) and 40% (95% CI: 16 to 57%; p =
      0.0019) reduction in days with pneumonia and vomiting respectively. WCBA in the
      HZn group also showed a statistically significant 9% fewer days with fever
      compared to LZn group. CONCLUSIONS: Biofortified wheat flour had a good
      compliance among children and WCBAs. Significant improvement on some of the self
      reported morbidity indicators suggests that evaluating longer-term effects of
      biofortification with higher grain zinc content would be more appropriate. TRIAL
      REGISTRATION: http://ctri.nic.in/Clinicaltrials/ , CTRI/2014/04/004527,
      Registered April 7, 2014.

PMID- 30219063
TI  - Modified triple pelvic osteotomy for adult symptomatic acetabular dysplasia:
      clinical and radiographic results at midterm follow-up.
AB  - BACKGROUND: Acetabular dysplasia is the most common cause of secondary arthritis
      of the hip joint. Achieving maximum restoration of the acetabular coverage and
      medialization of the femoral head remains difficult with the original Steel
      triple pelvic osteotomy for acetabular dysplasia in children and adults. This
      study intended to answer the following questions: (1) Are the midterm functional
      results of our modified procedure favorable, particularly in relation to Harris
      scores? and (2) On the basis of the Tonnis grade, does this procedure has a
      different effect on radiographic parameters and functional results at midterm
      follow-up? METHODS: This study included 26 consecutive adult patients with
      symptomatic acetabular dysplasia (28 hips) who underwent modified triple pelvic
      osteotomy through two incisions between July 2005 and June 2012. According to the
      preoperative Tonnis grade, the patients were divided into T0 (Tonnis grade 0), T1
      (Tonnis grade 1), and T2 (Tonnis grade 2) groups. Wiberg center-edge (CE) angle,
      Sharp acetabular angle, lateralization, and Harris scores were analyzed to assess
      the radiographic and clinical outcomes. RESULTS: The mean CE angle (28.43 degrees
      [+/- 3.58 degrees ], p < 0.05), Sharp acetabular angle (36.39 degrees  [+/- 3.26
      degrees ], p < 0.05), lateralization (16.82 mm [+/- 3.10 mm], p < 0.05), and
      Harris scores (89.07 [+/- 4.97], p < 0.05) at the last follow-up significantly
      improved compared to those preoperatively. Multiple comparisons of radiographic
      outcomes among the three groups indicated no significant difference (p < 0.05).
      Harris scores in group T2 were significantly lower than those in groups T0 (p <
      0.05) and T1 (p < 0.05). No major complication was observed. CONCLUSIONS: Our
      modified triple pelvic osteotomy for adult symptomatic acetabular dysplasia with
      early-stage osteoarthritis could lead to excellent radiographic outcomes, good
      clinical results, and lower complication rates.

PMID- 30219064
TI  - LMO3 promotes hepatocellular carcinoma invasion, metastasis and anoikis
      inhibition by directly interacting with LATS1 and suppressing Hippo signaling.
AB  - BACKGROUND: In this research, we aimed to investigate the biological functions of
      LIM domain only 3 (LMO3) in hepatocellular carcinoma (HCC) and uncover the
      underlying molecular mechanism in it. METHODS: HCC tissue microarray (n = 180)
      was used to analyze the correlation between LMO3 expression and
      clinicopathological findings. In vitro transwell matrigel invasion assay and
      annexin V anoikis assay in HCC cells were conducted to investigate LMO3 related
      biological functions. In vivo intrahepatic and lung metastasis models were used
      to determine the role of LMO3 in HCC metastasis. Quantitative real-time PCR,
      western blotting and immunohistochemical staining were performed to investigate
      the expression and mechanism of LMO3 in HCC. RESULTS: We found that the
      expression of LMO3 was significantly upregulated in HCC tissues, and it was
      closely related to clinicopathological findings and patient prognoses. Knockdown
      of LMO3 suppressed the invasion and anoikis inhibition of HCC cells in vitro.
      Meanwhile, the metastasis of SMMC-7721 cells was also suppressed by LMO3
      knockdown in vivo. Furthermore, we found that LMO3 knockdown increased the
      phosphorylation of YAP and LATS1, and decrease Rho GTPases activities. LMO3
      directly interacted with LATS1, and thus suppressed Hippo signaling. Recombinant
      LMO3 (rLMO3) protein administration decreased the phosphorylation of YAP and
      LATS1, and increased Rho GTPases activities. The inhibitors of the Hippo pathway
      abrogated rLMO3 protein-induced HCC cell invasion and anoikis inhibition.
      CONCLUSIONS: These results suggest that LMO3 promotes HCC cell invasion and
      anoikis inhibition by interacting with LATS1 and suppressing Hippo signaling.
      LMO3 may serve as a potential therapeutic target for HCC in future.

PMID- 30219065
TI  - Research capacity building frameworks for allied health professionals - a
      systematic review.
AB  - BACKGROUND: Building the capacity of allied health professionals to engage in
      research has been recognised as a priority due to the many benefits it brings for
      patients, healthcare professionals, healthcare organisations and society more
      broadly. There is increasing recognition of the need for a coordinated multi
      strategy approach to building research capacity. The aim of this systematic
      review was to identify existing integrated models and frameworks which guide
      research capacity building for allied health professionals working in publicly
      funded secondary and tertiary healthcare organisations. METHODS: A systematic
      review was undertaken searching five databases (Medline, CINAHL, Embase,
      AustHealth and Web of Science) using English language restrictions. Two authors
      independently screened and reviewed studies, extracted data and performed quality
      assessments using the Mixed Methods Appraisal Tool. Content and thematic analysis
      methods were used to code and categorise the data. RESULTS: A total of 8492
      unique records were screened by title and abstract, of which 20 were reviewed in
      full-text. One quantitative study and five qualitative studies were included,
      each of which describing a research capacity building framework. Three
      interconnected and interdependent themes were identified as being essential for
      research capacity building, including 'supporting clinicians in research',
      'working together' and 'valuing research for excellence'. CONCLUSIONS: The
      findings of this systematic review have been synthesised to develop a succinct
      and integrated framework for research capacity building which is relevant for
      allied health professionals working in publicly funded secondary and tertiary
      healthcare organisations. This framework provides further evidence to suggest
      that research capacity building strategies are interlinked and interdependent and
      should be implemented as part of an integrated 'whole of system' approach, with
      commitment and support from all levels of leadership and management. Future
      directions for research include using behaviour change and knowledge translation
      theories to guide the implementation and evaluation of this new framework. TRIAL
      REGISTRATION: The protocol for this systematic review has been registered with
      PROSPERO. The registration number is CRD42018087476 .

PMID- 30219066
TI  - Antimicrobial activities of flavonoid glycosides from Graptophyllum grandulosum
      and their mechanism of antibacterial action.
AB  - BACKGROUND: The search for new antimicrobials should take into account drug
      resistance phenomenon. Medicinal plants are known as sources of potent
      antimicrobial compounds including flavonoids. The objective of this investigation
      was to evaluate the antimicrobial activities of flavonoid glycosides from
      Graptophyllum grandulosum, as well as to determine their mechanism of
      antibacterial action using lysis, leakage and osmotic stress assays. METHODS: The
      plant extracts were prepared by maceration in organic solvents. Column
      chromatography of the n-butanol extract followed by purification of different
      fractions led to the isolation of five flavonoid glycosides. The antimicrobial
      activities of extracts/compounds were evaluated using the broth microdilution
      method. The bacteriolytic activity was evaluated using the time-kill kinetic
      method. The effect of extracts on the red blood cells and bacterial cell membrane
      was determined by spectrophotometric methods. RESULTS: Chrysoeriol-7-O-beta-D
      xyloside (1), luteolin-7-O-beta-D-apiofuranosyl-(1 -> 2)-beta-D-xylopyranoside
      (2), chrysoeriol-7-O-beta-D-apiofuranosyl-(1 -> 2)-beta-D-xylopyranoside (3),
      chrysoeriol-7-O-alpha-L-rhamnopyranosyl-(1 -> 6)-beta-D-(4"-hydrogeno sulfate)
      glucopyranoside (4) and isorhamnetin-3-O-alpha-L-rhamnopyranosyl-(1 -> 6)-beta-D
      glucopyranoside (5) were isolated from G. grandulosum and showed different
      degrees of antimicrobial activities. Their antibacterial activities against multi
      drug-resistant Vibrio cholerae strains were in some cases equal to, or higher
      than those of ciprofloxacin used as reference antibiotic. The antibacterial
      activities of flavonoid glycosides and chloramphenicol increased under osmotic
      stress (5% NaCl) whereas that of vancomycin decreased under this condition. V.
      cholerae suspension treated with flavonoid glycosides, showed a significant
      increase in the optical density at 260 nm, suggesting that nucleic acids were
      lost through a damaged cytoplasmic membrane. A decrease in the optical density of
      V. cholerae NB2 suspension treated with the isolated compounds was observed,
      indicating the lysis of bacterial cells. The tested samples were non-toxic to
      normal cells highlighting their good selectivity index. CONCLUSIONS: The results
      of the present study indicate that the purified flavonoids from G. glandulosum
      possess antimicrobial activities. Their mode of antibacterial activity is due to
      cell lysis and disruption of the cytoplasmic membrane upon membrane permeability.

PMID- 30219067
TI  - Facilitators and challenges in recruiting pregnant women to an infant obesity
      prevention programme delivered via telephone calls or text messages.
AB  - BACKGROUND: Recruitment of pregnant women into trials is a challenge exacerbated
      by a number of factors, including strict eligibility criteria. There has been
      little in-depth examination of the recruitment process to trials involving
      pregnant women. This paper presents the findings of a study conducted to identify
      facilitators and challenges in recruiting pregnant women to the Communicating
      Healthy Beginnings Advice by Telephone (CHAT) randomised controlled trial, which
      aims to reduce the prevalence of infant and childhood obesity. METHODS: Data were
      collected from (1) administration of a short questionnaire to women at the time
      of recruitment exploring women's reasons for consent and non-consent; (2)
      interviews with recruiters to capture recruiters' experiences of the recruitment
      process; and (3) analysis of field notes taken by recruiters on the number of
      women approached/recruited and reasons as to why they did not consent to
      participate. Data obtained were triangulated to gain insights into the process of
      recruiting pregnant women. RESULTS: A total of 1155 pregnant women (mean
      gestational age 31.5 weeks) were enrolled over 5 months. The main reasons for
      women consenting to participate in the study were convenience in programme
      delivery mode via telephone calls or text messages, altruism and because the
      programme was free of charge. The main reasons for women not consenting were lack
      of interest, language challenges/difficulty speaking English and some felt they
      did not need information and support due to prior experience as a mother.
      Facilitators included organisational support, rapport with recruiters and some
      women with no other children who needed advice. Despite the challenges, the mode
      of delivery of intervention via telephone calls or text messages, the minimal
      effort required of women to participate, organisational support from the lead
      site and recruiters' knowledge of and commitment towards the trial contributed
      towards successful recruitment. CONCLUSION: Despite some challenges in recruiting
      pregnant women to an infant obesity prevention programme, some of the
      facilitators in recruitment included mode of delivery of the intervention
      programme via telephone calls or text messages, the minimal effort required for
      women to participate, organisational support from the lead site, and recruiters'
      knowledge of and commitment towards the trial. TRIAL REGISTRATION: The CHAT RCT
      is registered with the Australian Clinical Trial Registry ( ACTRN12616001470482p
      ); Ethics Review Committee of Sydney Local Health District (Protocol No. X16-0360
      & LNR/16/RPAH/495).

PMID- 30219068
TI  - Localization of fat depots and cardiovascular risk.
AB  - Despite the existing preventative and therapeutic measures, cardiovascular
      diseases remain the main cause of temporary disability, long-term disability, and
      mortality. Obesity is a major risk factor for cardiovascular diseases and their
      complications. However, not all fat depots have the same inflammatory, paracrine,
      and metabolic activities. In addition, recent studies have indicated that the
      accumulation of visceral fat, rather than subcutaneous fat, is associated with
      increased cardiometabolic risk. However, there is also evidence that increasing
      the area of visceral fat can help protect against lipotoxicity. This review aims
      to discuss the contemporary literature regarding the characteristics of the
      visceral, epicardial, and perivascular fat depots, as well as their associations
      with cardiovascular disease.

PMID- 30219069
TI  - 'Telling our story... Creating our own history': caregivers' reasons for
      participating in an Australian longitudinal study of Indigenous children.
AB  - BACKGROUND: Improving the wellbeing of Indigenous populations is an international
      priority. Robust research conducted with Aboriginal and Torres Strait Islander
      peoples is key to developing programs and policies to improve health and
      wellbeing. This paper aims to quantify the extent of participation in a national
      longitudinal study of Aboriginal and Torres Strait Islander (Indigenous
      Australian) children, and to understand the reasons why caregivers participate in
      the study. METHODS: This mixed methods study uses data from Wave 6 of Footprints
      in Time, the Longitudinal Study of Indigenous Children. We conducted descriptive
      analysis of quantitative variables to characterise the sample and retention
      rates. We applied conventional content analysis to 160 caregivers' open-ended
      responses to the question, 'Why do you stay in the study?', identifying themes
      and overarching meta-themes. RESULTS: The study has maintained a high retention
      rate, with 70.4% (n = 1239/1671) of the baseline sample participating in the
      study's 6th wave. We identified seven themes related to why participants stay in
      the study: telling our story, community benefit, satisfaction, tracking Study
      Child's progress, study processes, receiving study gifts, and valuing what the
      study stands for. These related to two meta-themes: reciprocity, and trust and
      connection. Caregivers reported that participation was associated with benefits
      for their family and community as well as for the study. They identified specific
      features of the Footprints in Time study design that built and maintained trust
      and connection between participants and the study. CONCLUSIONS: Our findings
      support the assertion that Aboriginal and Torres Strait Islander people want to
      be involved in research when it is done 'the right way'. Footprints in Time has
      successfully recruited and retained the current-largest cohort of Aboriginal and
      Torres Strait Islander children in Australia through the use of participatory
      research methodologies, suggesting effective study implementation and processes.
      Participants indicated ongoing commitment to the study resulting from perceptions
      of reciprocity and development of trust in the study. Footprints in Time can
      serve as a successful model of Aboriginal and Torres Strait Islander health
      research, to promote good research practice and provides lessons for research
      with other Indigenous populations.

PMID- 30219070
TI  - "In the hospital, there will be nobody to pamper me": a qualitative assessment on
      barriers to facility-based delivery in post-Ebola Sierra Leone.
AB  - BACKGROUND: Sierra Leone has one of the highest maternal mortality rates in the
      world. Encouraging the use of skilled birth attendance in health facilities is an
      important step in the endeavor to increase the number of safe deliveries.
      However, public trust in health facilities has been greatly damaged during the
      Ebola epidemic outbreak in Sierra Leone in 2014/2015, and little is known about
      external and intrinsic barriers to facility-based delivery (FBD) in the country
      since the end of the Ebola epidemic. METHODS: We conducted a qualitative study on
      FBD in Princess Christian Maternity Hospital, Freetown, which is the national
      referral maternity hospital in Sierra Leone. We performed six focus group
      discussions with providers, pregnant women and recent mothers surrounding
      experiences, attitudes and behaviors regarding FBD and potential barriers.
      Discussions were tape recorded, transcribed and evaluated through content
      analysis. RESULTS: Women in our study were overall technically aware of the
      higher safety linked with FBD, but this often diverged from their individual
      desire to deliver in a supportive and trusted social and traditional environment.
      Close relatives and community members seemed to be highly influencial regarding
      birth practices. Many women associated FBD with negative staff attitudes and an
      undefined fear. Logistic issues regarding transportation problems or late
      referral from smaller health centers were identified as frequent barriers to FBD.
      CONCLUSIONS: More supportive staff attitudes and acceptance of an accompanying
      person throughout delivery could be promising approaches to increase women's
      confidence in FBDs. However, these approaches also imply revising health systems
      structures, like staff working conditions that are conducive for a friendly
      atmosphere, sufficient space in delivery wards allowing the women to bring a
      birth companion, or like the establishment of a reliable peripheral ambulance
      system to ensure transportation and fast referral.

PMID- 30219071
TI  - Exosomal miR-1290 is a potential biomarker of high-grade serous ovarian carcinoma
      and can discriminate patients from those with malignancies of other histological
      types.
AB  - BACKGROUND: microRNAs (miRNAs) stably exist in circulating blood encapsulated in
      extracellular vesicles such as exosomes; therefore, serum miRNAs have the
      potential to serve as novel cancer biomarkers. New diagnostic markers to detect
      high grade serous ovarian cancer (HGSOC) are urgently needed. The aim of this
      study was to identify miRNAs specific to HGSOC and analyze whether serum miRNA
      can discriminate HGSOC patients from healthy controls or patients with ovarian
      malignancies of other histological types. METHODS: Exosomes from ovarian cancer
      cell lines were collected and exosomal miRNAs extracted. miRNA microarray
      analysis revealed several elevated miRNAs specific to HGSOC. Among these, we
      focused on miR-1290. Sera from 70 ovarian cancer patients and 13 healthy controls
      were gathered and its expression levels detected by quantitative real-time
      polymerase chain reaction. RESULTS: In HGSOC patients, serum miR-1290 was
      significantly overexpressed compared to in healthy controls (3.52 fold; P =
      0.03), unlike in patients with ovarian cancers of other histological types. The
      relative expression of miR-1290 was higher in advanced stages of HGSOC than in
      early stages (4.23 vs. 1.58; P = 0.23). Its expression significantly decreased
      after operation (5.87 to 1.17; P < 0.01), indicating that this miRNA reflects
      tumor burden. A receiver operating characteristic curve analysis showed that at
      the cut-off of 1.20, the sensitivity and specificity were 63% and 85%
      respectively for discriminating patients with HGSOC (area under the curve [AUC] =
      0.71) from healthy controls, and at the cut-off of 1.55, the sensitivity and
      specificity were 47% and 85% respectively for discriminating patients with HGSOC
      (AUC = 0.76) from those with malignancies of other histological types.
      CONCLUSIONS: Serum miR-1290 is significantly elevated in patients with HGSOC and
      can be used to discriminate these patients from those with malignancies of other
      histological types; it is a new potential diagnostic biomarker for HGSOC.

PMID- 30219072
TI  - Dutch juvenile idiopathic arthritis patients, carers and clinicians create a
      research agenda together following the James Lind Alliance method: a study
      protocol.
AB  - BACKGROUND: Research on Juvenile Idiopathic Arthritis (JIA) should support
      patients, caregivers/parents (carers) and clinicians to make important decisions
      in the consulting room and eventually to improve the lives of patients with JIA.
      Thus far these end-users of JIA-research have rarely been involved in the
      prioritisation of future research. MAIN BODY: Dutch organisations of patients,
      carers and clinicians will collaboratively develop a research agenda for JIA,
      following the James Lind Alliance (JLA) methodology. In a 'Priority Setting
      Partnership' (PSP), they will gradually establish a top 10 list of the most
      important unanswered research questions for JIA. In this process the input from
      clinicians, patients and their carers will be equally valued. Additionally, focus
      groups will be organised to involve young people with JIA. The involvement of all
      contributors will be monitored and evaluated. In this manner, the project will
      contribute to the growing body of literature on how to involve young people in
      agenda setting in a meaningful way. CONCLUSION: A JIA research agenda established
      through the JLA method and thus co-created by patients, carers and clinicians
      will inform researchers and research funders about the most important research
      questions for JIA. This will lead to research that really matters.

PMID- 30219073
TI  - Nucleotide heterogeneity at the terminal ends of the genomes of two California
      Citrus tristeza virus strains and their complete genome sequence analysis.
AB  - BACKGROUND: The non-translated regions at the genome ends of RNA viruses serve
      diverse functions and can exhibit various levels of nucleotide (nt)
      heterogeneity. However, the extent of nt heterogeneity at the extreme termini of
      Citrus tristeza virus (CTV) genomes has not been comprehensively documented. This
      study aimed to characterize two widely prevalent CTV genotypes, T36-CA and T30
      CA, from California that have not been sequenced or analyzed substantially. The
      information obtained will be used in our ongoing effort to construct the
      infectious complementary (c) DNA clones of these viruses. METHODS: The terminal
      nts of the viral genomes were identified by sequencing cDNA clones of the plus-
      and/or minus-strand of the viral double-stranded (ds) RNAs generated using 5' and
      3' rapid amplification of cDNA ends. Cloned cDNAs corresponding to the complete
      genome sequences of both viruses were generated using reverse transcription
      polymerase chain reactions, sequenced, and subjected to phylogenetic analysis.
      RESULTS: Among the predominant terminal nts identified, some were identical to
      the consensus sequences in GenBank, while others were different or unique.
      Remarkably, one of the predominant 5' nt variants of T36-CA contained the
      consensus nts "AATTTCAAA" in which a highly conserved cytidylate, seen in all
      other full-length T36 sequences, was absent. As expected, but never
      systematically verified before, unique variants with additional nt (s)
      incorporated upstream of the 5' terminal consensus nts of T36-CA and T30-CA were
      also identified. In contrast to the extreme 5' terminal nts, those at the extreme
      3' termini of T36-CA and T30-CA were more conserved compared to the reference
      sequences, although nt variants were also found. Notably, an additional
      thymidylate at the extreme 3' end was identified in many T36-CA sequences.
      Finally, based on pairwise comparisons and phylogenetic analysis with multiple
      reference sequences, the complete sequences of both viruses were found to be
      highly conserved with those of the respective genotypes. CONCLUSIONS: The extreme
      terminal nts in the T36-CA and T30-CA genomes were identified, revealing new
      insights on the heterogeneity of these CTV genomic regions. T36-CA and T30-CA
      were the first and the second genotypes, respectively, of CTV originating from
      California to be completely sequenced and analyzed.

PMID- 30219075
TI  - Influencing factors of inequity in health services utilization among the elderly
      in China.
AB  - BACKGROUND: With the rise of the aging population, it is particularly important
      for health services to be used fairly and reasonably in the elderly. This study
      aimed to assess the present inequality and horizontal inequity for health service
      use among the elderly in China and to identify the main determinants associated
      with the disparity. METHODS: This cross-sectional study was based on the sample
      of the survey of the China Health and Retirement Longitudinal Study (CHARLS) for
      2015. The elderly was defined as individuals aged 60 and above, with a total of
      7836 participants. We used the concentration index (CI) and the horizontal
      inequity (HI) to measure the inequity of the utilization of health services. The
      method of concentration index decomposition was utilized to measure the
      contribution of various influential factors to the overall unfairness. RESULTS:
      The CI for the probability and the frequency of outpatient use were 0.1102 and
      0.1015, respectively, and the corresponding values of inpatient use were 0.2777
      and 0.2980, respectively. The household consumption expenditure disparity was the
      greatest inequality factor favoring the better-off. The Urban Employee Basic
      Medical Insurance made a pro-wealth contribution to inequality in frequency of
      health services utilization (17.58% for outpatient and 13.40% for inpatient). The
      contributions of New Rural Cooperative Medical Scheme on reducing unfairness in
      inpatient use were limited (- 2.23% for probability of inpatient use and - 5.89%
      for frequency of inpatient use). CONCLUSIONS: There was a strong pro-rich
      inequality in both the probability and the frequency of use for health services
      among the elderly in China. The medical insurance was not enough to address this
      inequity, and different medical insurance schemes had different effects on the
      unfairness of health service utilization.

PMID- 30219077
TI  - Increased expression of claudin-17 promotes a malignant phenotype in hepatocyte
      via Tyk2/Stat3 signaling and is associated with poor prognosis in patients with
      hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer
      death in Asia; however, the molecular mechanism in its tumorigenesis remains
      unclear. Abnormal expression of claudins (CLDNs), a family of tight junction (TJ)
      proteins, plays an important role in the metastatic phenotype of epithelial
      derived tumors by affecting tight junction structure, function and related
      cellular signaling pathways. In a previous study, we used a tissue chip assay to
      identify CLDN17 as an upregulated gene in HCC. Here we aimed to use molecular
      biology technology to explore the effect of CLDN17 on the malignant phenotype of
      HCC and the underlying molecular mechanism, with the objective of identifying a
      new target for HCC treatment and the control of HCC metastasis. METHOD: The
      expression levels of CLDN17 in HCC tissues and histologically non-neoplastic
      hepatic tissues were explored by immunohistochemistry. Stable transfection of the
      hepatocyte line HL7702 with CLDN17 was detected by real-time polymerase chain
      reaction (PCR), western blotting and immunofluorescence. The impact of CLDN17 on
      the malignant phenotype of HL7702 cells in vitro was assessed by a Cell Counting
      Kit-8 (CCK8) assay, a Transwell assay and a wound-healing experiment. Western
      blotting was utilized to detect the activation state of Tyrosine kinase 2 (Tyk2)
      / signal transducer and activator of transcription3 (Stat3) pathway. A Tyk2 RNA
      interference (RNAi) was utilized to determine the impact of the Tyk2/Stat3
      signaling pathway on the malignant phenotype of hepatocytes. RESULTS: In this
      work, our research group first found that CLDN17 was highly expressed in HCC
      tissues and was associated with poor prognosis. In addition, we demonstrated that
      CLDN17 affected the Stat3 signaling pathway via Tyk2 and ultimately enhanced the
      migration ability of hepatocytes. CONCLUSION: In conclusion, we confirmed that
      the upregulated expression of CLDN17 significantly enhances the migration ability
      of hepatocytes in vitro and we found that the activation of the Stat3 pathway by
      Tyk2 may an important mechanism by which CLDN17 promotes aggressiveness in
      hepatocytes.

PMID- 30219074
TI  - Organoid technology and applications in cancer research.
AB  - During the past decade, the three-dimensional organoid technology has sprung up
      and become more and more popular among researchers. Organoids are the miniatures
      of in vivo tissues and organs, and faithfully recapitulate the architectures and
      distinctive functions of a specific organ.These amazing three-dimensional
      constructs represent a promising, near-physiological model for human cancers, and
      tremendously support diverse potential applications in cancer research. Up to
      now, highly efficient establishment of organoids can be achieved from both normal
      and malignant tissues of patients. Using this bioengineered platform, the links
      of infection-cancer progression and mutation-carcinogenesis are feasible to be
      modeled. Another potential application is that organoid technology facilitates
      drug testing and guides personalized therapy. Although organoids still fail to
      model immune system accurately, co-cultures of organoids and lymphocytes have
      been reported in several studies, bringing hope for further application of this
      technology in immunotherapy. In addition, the potential value in regeneration
      medicine might be another paramount branch of organoid technology, which might
      refine current transplantation therapy through the replacement of irreversibly
      progressively diseased organs with isogenic healthy organoids.In conclusion,
      organoids represent an excellent preclinical model for human tumors, promoting
      the translation from basic cancer research to clinical practice. In this review,
      we outline organoid technology and summarize its applications in cancer research.

PMID- 30219076
TI  - Partner influences on young women's risky drug and sexual behavior.
AB  - BACKGROUND: Adolescent girls with a history of maltreatment are at heightened
      risk for health-risking behaviors, including unsafe sexual behaviors and drug
      use. However, few studies have examined the views of this population in regard to
      sexual partner choice, sexual behaviors, and decisions to use drugs with sexual
      partners. METHODS: We conducted 15 semistructured, open-ended qualitative
      interviews with young women ages 18-24 with a history of maltreatment and asked
      them to reflect on their experiences as adolescents. We used the constant
      comparison method to group the qualitative coded data into themes. RESULTS:
      Analysis of the interviews suggested that adolescent girls with maltreatment
      histories often report that they chose partners who are promotive of risky drug
      and sexual behavior. The interviews also provided insight into why this
      population is likely to use drugs with their partner and why they might be
      hesitant to talk about or practice safe sex with their partner. CONCLUSION: The
      young women's feedback highlighted five areas where adolescent girls with
      maltreatment histories could benefit: (a) provision of information about partner
      characteristics that are promotive of both risky behavior and those that are
      linked to healthy relationships, (b) provision of information about how one's
      partner can influence one's own drug use,

PMID- 30219078
TI  - PD1hi cells associate with clusters of proliferating B-cells in marginal zone
      lymphoma.
AB  - BACKGROUND: Abnormally sustained immune reactions drive B-cell proliferation in
      some cases of marginal zone lymphoma but the CD4+ T-cell subsets, which are
      likely to contribute to the B-cell responses in the tumour microenvironment, are
      not well characterised and neither has the spatial distribution of the different
      subsets in involved lymph nodes been investigated. METHODS: Employing a workflow
      of multiplex semi-automated immunohistochemistry combined with image processing
      we investigated association between infiltrating T-cells and proliferating
      lymphoma B-cells. RESULTS: Both total numbers of activating follicular helper
      (Tfh) cells (defined by high expression of PD1) and suppressive regulatory (Treg)
      T-cells (defined by FOXP3+ expression) and the Tfh:Treg ratio, assessed over
      relatively large areas of tissue, varied among cases of marginal zone lymphoma.
      We determined spatial distribution and demonstrated that PD1hi cells showed
      significantly more clustering than did FOXP3+. To investigate the association of
      infiltrating T-cells with lymphoma B-cells we employed Pearson correlation and
      Morisita-Horn index, statistical measures of interaction. We demonstrated that
      PD1hi cells were associated with proliferating B-cells and confirmed this by
      nearest neighbour analysis. CONCLUSIONS: The unexpected architectural complexity
      of T-cell infiltration in marginal zone lymphoma, revealed in this study, further
      supports a key role for Tfh cells in driving proliferation of lymphoma B-cells.
      We demonstrate the feasibility of digital analysis of spatial architecture of T
      cells within marginal zone lymphoma and future studies will be needed to
      determine the clinical importance of these observations.

PMID- 30219079
TI  - Mast cells and mast cell tryptase enhance migration of human lung fibroblasts
      through protease-activated receptor 2.
AB  - BACKGROUND: Mast cells may activate fibroblasts and contribute to remodeling
      processes in the lung. However, the mechanism behind these actions needs to be
      further investigated. Fibroblasts are major regulators of on-going remodeling
      processes. Protease activated receptor 2 (PAR2) expressed by fibroblasts may be
      activated by serine proteases, such as the mast cell mediator tryptase. The
      objective in this study was to investigate the effects of mast cells and
      specifically mast cell tryptase on fibroblast migration and the role of PAR2
      activation. METHODS: Human lung fibroblasts (HFL-1) were cultured together with
      human peripheral blood-derived mast cells or LAD2 mast cells and stimulated with
      either conditioned medium from LAD2 cells or tryptase. Analyses of immunological
      stimulation of mast cells by IgE/anti IgE in the co-culture system were also
      performed. The importance of PAR2 activation by mast cells and mast cell tryptase
      for the migratory effects of fibroblasts was investigated by pre-treatment with
      the PAR2 antagonist P2pal-18S. The expression of PAR2 was analyzed on fibroblasts
      and mast cells. RESULTS: The migratory capacity of HFL-1 cells was enhanced by
      blood-derived mast cells (p < 0.02), LAD2 cells (p < 0.001), conditioned medium
      (p < 0.05) and tryptase (p < 0.006). P2pal-18S decreased the induced migration
      caused by mast cells (p < 0.001) and tryptase (p < 0.001) and the expression of
      PAR2 was verified in HFL-1 cells. Mast cells immunologically stimulated with
      IgE/Anti IgE had no further effects on fibroblast migration. CONCLUSIONS: Mast
      cells and the mast cell mediator tryptase may have crucial roles in inducing lung
      fibroblast migration via PAR-2 activation, which may contribute to remodeling
      processes in chronic lung diseases.

PMID- 30219080
TI  - The quality of anti-malarial medicines in Embu County, Kenya.
AB  - BACKGROUND: Malaria is a major health problem in sub-Saharan Africa where over
      90% of the world's malaria cases occur. Artemisinin-based combination therapy
      (ACT) is recommended by the World Health Organization as first-line and second
      line treatments for uncomplicated falciparum malaria. However, there are a
      growing number of reports of sub-standard and falsified anti-malarial medicines
      in sub-Saharan Africa. METHODS: A cross-sectional study was conducted in Embu
      County, Kenya on the quality of anti-malarial medicines available in public and
      private facilities. Sampling of anti-malarial medicines from public and private
      hospitals, health centers and pharmacies was conducted between May and June 2014.
      Quality control tests were performed at the Drug Analysis and Research Unit,
      University of Nairobi, using ultraviolet spectrophotometry and high-performance
      liquid chromatography. A test for microbial load was also conducted for
      suspension formulations. RESULTS: A total of 39 samples were collected from
      public and private facilities across the Embu County. A visual inspection of the
      medicines showed no signs of sub-standard or falsification. All ACT passed
      identification, assay and dissolution tests. Of 11 suspension samples collected,
      none failed the microbial load test although one sample had 50 colony forming
      units (cfu). No oral artemisinin monotherapy medicines were encountered during
      the survey. Amodiaquine and chloroquine monotherapy products accounted for 5% of
      the collected samples, despite their ban in Kenya. Two herbal anti-malarial
      formulations were collected during the survey. Sulfadoxine/pyrimethamine (SP) was
      also found to be available use for malaria treatment, not in accordance with
      malaria treatment guidelines. CONCLUSION: All the anti-malarial drugs analysed in
      this study passed the quality control tests. This is encouraging given the high
      malaria burden in Kenya. Regulatory actions are required to counter SP and herbal
      products for malaria treatment.

PMID- 30219081
TI  - Change in health and social factors in mid-adulthood and corresponding changes in
      leisure-time physical inactivity in a prospective cohort.
AB  - BACKGROUND: To identify whether changes in adult health and social factors are
      associated with simultaneous changes in inactivity. METHODS: Health, social
      factors and leisure-time inactivity (activity frequency < 1/week) were self
      reported at 33y and 50y in the 1958 British birth cohort (N = 12,271). Baseline
      (33y) health and social factors and also patterns of change in factors 33y-to-50y
      were related to inactivity 33y-to-50y (never inactive, persistently inactive,
      deteriorating to inactivity, or improving from inactivity) using multinomial
      logistic regression. RESULTS: Approximately 31% were inactive at 33y and 50y; 35%
      changed status 33y-to-50y (17% deteriorating to inactivity, 18% improving from
      inactivity). Baseline poor health and obesity were associated with subsequent
      (33y-to-50y) inactivity; e.g. for poor health, relative risk ratios (RRRs) for
      deteriorating to inactivity (vs never inactive) and improving from inactivity (vs
      persistently inactive) were 1.38(1.16,1.64) and 0.77(0.63,0.94) respectively.
      Adverse changes in health and weight were associated with simultaneous adverse
      changes in inactivity; e.g. worsening health (vs always good/excellent health)
      was associated with higher risk of deteriorating to inactivity
      (RRR:2.20(1.85,2.62)) and lower risk of improving from inactivity
      (RRR:0.61(0.49,0.77)). However, improving health and weight loss were not
      associated with improving from inactivity. Worsening self-efficacy 33y-to-50y was
      associated with lower risk of improving from inactivity; there was no association
      between improving self-efficacy and inactivity change. Downward social mobility
      was not associated with deteriorating to or improving from inactivity. Changes in
      depression symptom level, marriage/co-habitation or parenthood 33y-to-50y were
      not associated with inactivity changes. No associations were observed for
      employment. CONCLUSIONS: Associated changes in mid-life health factors with
      deleterious inactivity changes, highlight the importance of maintaining health,
      weight and self-efficacy across adulthood to deter inactivity.

PMID- 30219083
TI  - Microbiological and clinical profile of infective endocarditis patients: an
      observational study experience from tertiary care center Karachi Pakistan.
AB  - BACKGROUND: The study analyzed microbiological and antimicrobial susceptibility
      profile of organisms isolated from patients with infective endocarditis (2015-17)
      and compared disease outcomes in cohorts of endocarditis patient with history of
      prior invasive vascular intervention (high risk group) vs those without (native
      valve group). We hypothesized that high risk group would be more likely to have
      severe disease outcomes. METHODS: This was a prospective cohort study (2015-17).
      All blood and cardiac tissue samples of enrolled patients suspected of
      endocarditis according to modified Duke's criteria were followed for
      microbiological and antimicrobial susceptibility profile. The high risk group was
      compared with the native valve group with 90 day follow up to determine
      difference in clinical course and outcome in terms of disease severity (defined
      as any patient with endocarditis undergoing surgical management, readmission or
      dying). The data was analyzed using SPSS 21.0 software and chi-square test. 90
      day mortality was calculated using Kaplan Meier survival curves. RESULTS: Total
      104 patients with endocarditis were enrolled. Overall culture positivity rate was
      71.2%. Streptococcus species were the most common isolate (36.7%), followed by S.
      aureus (17.3%) cases. In Streptococcus species, 14.2% showed intermediate
      susceptibility to penicillin. Thirty six patients were included in the cohort
      analysis. A poor outcome was seen in 85.7% high risk group as compared to 50% of
      native valve group. The overall mortality rate was 19.4%. CONCLUSIONS: We found
      Streptococcus species to be the predominant pathogen for endocarditis overall.
      However Staphylococcus aureus predominated native valve group. High risk group
      showed more complicated clinical course.

PMID- 30219082
TI  - Biotin and chromium histidinate improve glucose metabolism and proteins
      expression levels of IRS-1, PPAR-gamma, and NF-kappaB in exercise-trained rats.
AB  - BACKGROUND: Chromium histidinate (CrHis) and biotin are micronutrients commonly
      used to improve health by athletes and control glycaemia by patients with
      diabetes. This study investigates the effects of 8-week regular exercise training
      in rats together with dietary CrHis and biotin supplementation on glucose, lipids
      and transaminases levels, as well as protein expression levels of peroxisome
      proliferator-activated receptor gamma (PPAR-gamma), insulin receptor substrate-1
      (IRS-1) and nuclear transcription factor kappa B (NF-kappaB). METHODS: A total of
      56 male Wistar rats were randomly divided into 8 groups of 7 animals each and
      treated as follows: Control, CrHis, Biotin, CrHis+Biotin, Exercise,
      CrHis+Exercise, Biotin+Exercise, and CrHis+Biotin+Exercise. The doses of CrHis
      and biotin were 400 MUg/kg and 6 mg/kg of diet, respectively. The training
      program consisted of running at 30 m/min for 30 min/day at 0% grade level, 5 days
      per week, once a day for 6 weeks. Serum glucose, total cholesterol (TC), high
      density lipoprotein cholesterol (HDL), triglycerides (TG), aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured
      with an automatic biochemical analyzer. Muscle and liver PPAR-gamma, IRS-1 and NF
      kappaB expressions were detected with real-time polymerase chain reaction.
      RESULTS: Regular exercise significantly (p < 0.001) decreased glucose, TC and TG
      levels, but increased HDL cholesterol. Dietary CrHis and biotin supplementation
      exhibited a significant (p < 0.001) decrease in glucose (effect size = large; n2
      = 0.773) and TG (effect size = large; n2 = 0.802) levels, and increase in HDL
      cholesterol compared with the exercise group. No significant change in AST and
      ALT (effect size = none) levels was recorded in all groups (p > 0.05).
      CrHis/biotin improves the proteins expression levels of IRS-1, PPAR-gamma, and NF
      kappaB (effect size: large for all) in the liver and muscle of sedentary and
      regular exercise-trained rats (p < 0.001). CONCLUSIONS: CrHis/biotin
      supplementation improved serum glucose and lipid levels as well as proteins
      expression levels of PPAR-gamma, IRS-1 and NF-kappaB in the liver and muscle of
      exercise-trained rats, with the highest efficiency when administered together.
      CrHis/biotin may represent an effective nutritional therapy to improve health.

PMID- 30219084
TI  - Detection of specific gene rearrangements by fluorescence in situ hybridization
      in 16 cases of clear cell sarcoma of soft tissue and 6 cases of clear cell
      sarcoma-like gastrointestinal tumor.
AB  - BACKGROUND: Clear cell sarcoma of soft tissue (CCSST) and clear cell sarcoma-like
      gastrointestinal tumor (CCSLGT) are malignant mesenchymal tumors that share some
      pathological features, but they also have several different characteristics. They
      are well known to express chimeric fusions of Ewing sarcoma breakpoint region 1
      (EWSR1) and cAMP response element-binding protein (CREB) family members; namely,
      EWSR1-activating transcription factor 1 (ATF1) and EWSR1-CREB1. In addition,
      recent studies have suggested the presence of other fusions. METHODS: We used
      fluorescence in situ hybridization to detect specific rearrangements including
      EWSR1, ATF1, CREB1, and cAMP response element modulator (CREM) in 16 CCSST and 6
      CCSLGT cases. We also used reverse transcription polymerase chain reaction (RT
      PCR) to detect specific chimeric fusions of EWSR1-ATF1 and EWSR1-CREB1 using
      fresh tumor samples in available cases. RESULTS: A total of 15 of 16 CCSST cases
      (93.8%) had EWSR1 rearrangement, of which 11 (68.8%) also had ATF1 rearrangement,
      suggestive of the presence of EWSR1-ATF1 fusions. One CCSST case (6.3%) was found
      to have EWSR1 and CREM rearrangements, and 4 of 6 CCSLGT cases (66.7%) had EWSR1
      rearrangement, of which 2 (33.3%) showed ATF1 rearrangement and the other 2 cases
      (33.3%) showed CREB1 rearrangement. These cases most likely had EWSR1-ATF1 and
      EWSR1-CREB1 fusions, respectively. RT-PCR was performed in 8 available cases,
      including 6 CCSSTs and 2 CCSLGTs. All CCSSTs showed EWSR1-ATF1 fusions. Among the
      2 CCSLGT cases, one had EWSR1-ATF1 fusion and the other had EWSR1-CREB1 fusion.
      CONCLUSIONS: Rearrangements of EWSR1 and ATF1 or EWSR1-ATF1 fusion were
      predominantly found in CCSST, whereas those of EWSR1 and CREB1 or EWSR1-CREB1
      tended to be detected in CCSLGT. A novel CREM fusion was also detected in a few
      cases of CCSST and CCSLGT. The cases in which EWSR1 rearrangement was detected
      without definitive partner genes should be considered for the presence of CREM
      rearrangement.

PMID- 30219085
TI  - MicroRNA let-7b inhibits keratinocyte differentiation by targeting IL-6 mediated
      ERK signaling in psoriasis.
AB  - BACKGROUND: The extensive involvement of microRNA (miRNA) in the pathophysiology
      of psoriasis is well documented. However, in order for this information to be
      useful in therapeutic manipulation of miRNA levels, it is essential that detailed
      functional mechanisms are elucidated. This study aimed to explore the effects of
      IL-6 targeting by let-7b and ERK1/2 mediated signaling on keratinocyte
      differentiation in psoriasis. METHODS: Following imiquimod cream (IMQ)
      application to let-7bTG (keratinocyte-specific let-7b overexpression mouse) and
      control mice for 7 days, we analyzed erythema, scaling and thickening of skin. A
      dual luciferase reporter assay and bioinformatics was carried out to detect
      target gene of let-7b. Additionally, the differentiation markers were measured.
      Immunohistochemistry analyses demonstrate a relationship of let-7b with IL-6 and
      ERK signaling. RESULTS: we found let-7bTG inhibits acanthosis and reduces the
      disease severity by treatment with IMQ compared to wild-type mice. Further study
      illustrated that let-7b promotes differentiation of keratinocytes in vivo and in
      vitro. Using bioinformatics and reporter gene assays, we found that IL-6 is a
      target gene of let-7b. In psoriasis, high expression levels of IL-6 lead to
      increased acivation of p-ERK1/2. High levels of let-7bTG transgene expression
      suppresses IL-6 expression and leads to increased keratinocyte differentiation.
      Moreover, let-7b acts as an upstream negative regulator of the ERK signaling
      pathway in keratinocytes of psoriasis. CONCLUSIONS: Our result reveals a
      previously unknown mechanism for regulation of IL-6 levels during psoriasis by
      let-7b and highlights a critical role for the ERK1/2 signaling pathway in
      epidermal differentiation during psoriasis. TRIAL REGISTRATION: The ethical
      approval for this study was from the Affiliated Hospital of Medical University of
      Anhui _ Fast_ PJ2017-11-14.

PMID- 30219086
TI  - Electroacupuncture to treat with Overactive Bladder in Postmenopausal Women:
      study protocol for a multicenter, randomized, controlled, parallel clinical
      trial.
AB  - BACKGROUND: Electroacupuncture has been used for treatment in patients with
      overactive bladder. This study was conducted to evaluate the efficacy and safety
      of electroacupuncture for treating overactive bladder of postmenopausal women.
      METHODS/DESIGN: This is a multicenter, randomized controlled, parallel clinical
      trial. Two hundred ninety participants with overactive bladder syndrome will be
      recruited from Dongguk University Bundang Oriental Hospital and Cheonan Korean
      Medicine Hospital of Daejeon University and randomly allocated into one of two
      groups in a 1:1 ratio. One group will receive electroacupuncture (EA) and the
      other acupuncture (AC). The allocation will be concealed from both participants
      and assessors. The study period will be about 10 weeks, including 6 weeks of
      electroacupuncture or acupuncture treatment and a four week follow-up period.
      Both EA group and AT group will undergo acupuncture at 7 fixed points, and the EA
      group will undergo electronic stimulation at 6 points. The primary outcome will
      be the average number of micturitions per 24 h based on a 3-day bladder diary.
      The secondary outcome will comprise the 3-day bladder diary, the overactive
      bladder symptom score and the results of the King's health questionnaire.
      DISCUSSION: The results of this trial will provide information regarding the
      efficacy and safety of electroacupuncture for treating overactive bladder in
      postmenopausal women. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03260907 .
      Registered on 24 August 2017.

PMID- 30219087
TI  - Patterns of cognitive function in middle-aged and elderly Chinese adults-findings
      from the EMCOA study.
AB  - BACKGROUND: The principal aim of this study was to demonstrate the gender
      specific cognitive patterns among middle-aged and elderly Chinese adults,
      investigate the risk factors on global and domain-specific cognitive performance
      in men and women, respectively, and report demographically adjusted norms for
      cognitive tests. METHODS: The Effects and Mechanism of Cholesterol and Oxysterol
      on Alzheimer's disease (EMCOA) study enrolled 4573 participants aged 50-70 years
      in three Chinese cities. All participants underwent an extensive
      neuropsychological test battery. Composite scores for specific domains were
      derived from principal component analysis (PCA). Multivariate linear regression
      models were used to determine gender-specific risk factors and demographically
      adjusted normative data. RESULTS: Three cognitive domains of verbal memory,
      attention/processing speed/executive function, and cognitive flexibility were
      extracted. A female advantage in verbal memory was observed regardless of age,
      whereas men tended to outperform women in global cognition and
      attention/processing speed/executive function. The effects of education on women
      were more substantial than men for general cognition and attention/processing
      speed/executive function. For all the cognitive tests, regression-based and
      demographically adjusted normative data were calculated. CONCLUSIONS: There is a
      need for gender-specific intervention strategies for operationalizing cognitive
      impairment. TRIAL REGISTRATION: EMCOA, ChiCTR-OOC-17011882 . Retrospectively
      registered on 5 July 2017.

PMID- 30219088
TI  - Total thyroidectomy (Tx) versus thionamides (antithyroid drugs) in patients with
      moderate-to-severe Graves' ophthalmopathy - a 1-year follow-up: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Graves' disease (GD) is characterized by thyrotoxicosis and goiter
      and arises through circulating autoantibodies that bind to, and stimulate, the
      thyroid hormone receptor (TSHR). A temporal relation between the onset of
      hyperthyroidism and the onset of ophthalmopathy, a common extrathyroidal
      manifestation, has been demonstrated. Graves' ophthalmopathy (GO) is typically
      characterized by an inflammation and expansion of the extraocular muscles and an
      increase in retroorbital fat. There are currently three forms of therapies
      offered for hyperthyroidism caused by Graves' disease: antithyroid drugs (ATD)
      (thionamides), radioiodine ablation (RAI) and thyroidectomy (Tx). To date, there
      is no clear recommendation on the treatment of Graves' disease and GO, mainly due
      to the individuality of the disease in each patient. The aim of the study is to
      examine the difference in the outcome of GO in patients with moderate-to-severe
      GO who receive Tx versus further ATD after suffering their first relapse of GO,
      or in which GO stays the same following the initial decrease in ATD therapy after
      6 months. METHODS/DESIGN: This prospective randomized clinical trial with
      observer-blinded analysis will analyze 60 patients with moderate-to-severe GO who
      receive Tx versus ATD without surgery. Main outcome variables include: muscle
      index measurements via ultrasound and thyroid antibody levels. Additional outcome
      variables include: Clinical Activity Score (CAScore), NOSPECS score, superonasal
      index measurements via ultrasound, and quality of life score. DISCUSSION: This
      study should allow for better therapeutic choices in patients with moderate-to
      severe GO. In addition, it should demonstrate whether the outcome of GO in
      patients with moderate-to-severe GO is better in those who receive early Tx
      versus further ATD. Furthermore, this study will aim to establish a standard
      glucocorticoid scheme before and after Tx in patients with moderate-to-severe EO.
      TRIAL REGISTRATION: Eudra-CT: 2015-003515-38; Medical University of Vienna
      Protocol Record 1839/2015. Date of Ethics Committee approval: 19 January 2017.
      Registered on 27 January 2017.

PMID- 30219089
TI  - Sensitivity and specificity of using trial-of-antibiotics versus sputum
      mycobacteriology for diagnosis of tuberculosis: protocol for a systematic
      literature review.
AB  - BACKGROUND: Suboptimal diagnostics for pulmonary tuberculosis (PTB) drives use of
      'trial-of-antibiotics (non-tuberculosis)' in an attempt to distinguish PTB
      patients from those with bacterial lower respiratory tract infection (LRTI). The
      underlying assumption-that patients with LRTI will report 'response' to broad
      spectrum antibiotics, while those with PTB will not-has minimal evidence base for
      such a widely used intervention. Numerous potential causes of misclassification
      include bacterial super-infection of active PTB, placebo effect, and
      antimicrobial resistance (AMR). The main aim of this systematic review is to
      collate available evidence on the performance of trial-of-antibiotics as a
      diagnostic test and to explore the timing, interpretation, and decision-making
      process. METHODS: We will search MEDLINE, Embase, and Global Health using the
      Ovid platform for published studies that recruited adults being investigated for
      PTB, performed trial-of-antibiotics accompanied by mycobacteriological
      investigations, and reported both diagnostic test outcomes at the individual
      level. Following article selection, two authors will independently review titles
      and abstracts against eligibility criteria then perform full-text screening and
      extraction into a spreadsheet. We will conduct a risk of bias assessment at the
      level of the study using QUADAS-2 (University of Bristol) tool that assesses
      diagnostic evaluation work in four domains: (1) patient selection, (2) the index
      test, (3) the reference standard, and (4) patient flow and timing of tests. We
      will perform a narrative synthesis and, where possible, meta-analyses addressing
      our primary outcome. Our protocol adheres to the standards recommended by the
      PRISMA-P. DISCUSSION: Pooling all available evidence on the accuracy, approach,
      and interpretation of results of trial-of-antibiotics in the context of PTB
      diagnosis will meet an urgent need, considering the widespread utilisation and
      potential for antimicrobial resistance. We therefore believe that our findings
      will have impact on policy and that they will inform the design of future
      detailed investigations into this important diagnostic approach. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42017083915.

PMID- 30219090
TI  - Elbow arthroscopy in children and adolescents: analysis of outcome and
      complications.
AB  - BACKGROUND: Chondral or osteochondral lesions, post-traumatic contracture and
      loose bodies of the elbow are often associated with chronic pain, stiffness,
      repetitive swelling and joint blockages. Therefore, arthroscopy of the elbow is
      often used in the elderly for the treatment of osteochondral defects or
      arthrolysis. There are only a few reports and studies about arthroscopic therapy
      of the elbow in children and adolescents. This study assesses the clinical
      outcome of arthroscopic therapy in this age group. METHODS: In a retrospective
      study, children and adolescents who underwent an elbow arthroscopy in the period
      from 2010 to 2014 were included. The children were evaluated using the validated
      outcome measures Mayo Elbow Performance Score (MEPS), range of motion, pain on
      visual analog scale (VAS), Oxford Elbow Score (OES), quick dash and postoperative
      satisfaction. Furthermore, all complications were analyzed. RESULTS: In total, 27
      patients were included. The mean (range) age was 14 (11-17) years, with a follow
      up of 45 months. Fourteen (52%) were female and thirteen children (48%) were
      male. Twenty children had an arthroscopy due to osteochondritis dissecans and
      seven children for post-traumatic pain and stiffness. The mean (standard
      deviation) MEPS improved from 65 (15) to 96 (8; p = .005). The OES and quick dash
      were 93 and 5.4. The mean extension improved from - 15 degrees  (+/- 13.8) to 3
      degrees  (+/- 10.2; p < .001). The mean flexion improved from 131 degrees  (+/-
      13.4) to 137 degrees  (+/- 9.5; p = .003). Average pain on VAS was postoperative
      .2 (+/- .5), and 81.5% of all children had excellent or good results. There were
      no complications such as damage of nerves or blood vessels observed. CONCLUSION:
      Elbow arthroscopy is an appropriate and safe treatment option in children and
      adolescents with good and excellent postoperative results.

PMID- 30219091
TI  - Chilaiditi syndrome - a rare case of pneumoperitoneum in the emergency
      department: a case report.
AB  - BACKGROUND: Pneumoperitoneum poses an important diagnostic sign determining the
      urgency of management of patients in an emergency department. Chilaiditi sign is
      a rare radiologic finding of large intestines transposition between the diaphragm
      and the liver. If the patient becomes symptomatic, then the condition is called
      Chilaiditi syndrome. CASE PRESENTATION: We present a rare case of a 49-year-old
      Egyptian man who presented to our emergency department complaining of cough and
      vague abdominal discomfort who was found to have Chilaiditi syndrome diagnosed
      radiologically by computed tomography scan. He was conservatively managed rather
      than undergoing invasive non-warranted diagnostic and therapeutic testing that
      may have resulted in increased morbidity. CONCLUSIONS: A review of the current
      literature on Chilaiditi syndrome is provided with a focus on increasing the
      familiarity of health care professionals with the conditions and stressing the
      importance of a physical examination in evaluating patients with what appears to
      be air under the diaphragm.

PMID- 30219092
TI  - Survival estimates stratified by the Nottingham Prognostic Index for early breast
      cancer: a systematic review and meta-analysis of observational studies.
AB  - BACKGROUND: Estimates of survival for women diagnosed with early staged breast
      cancer are available based on stratification into prognostic categories defined
      using the Nottingham Prognostic Index (NPI). This review aimed to identify and
      summarize the estimated survival statistics from separate sources in the
      literature and to explore the extent of between-study heterogeneity in survival
      estimates. METHODS: Observational studies in women diagnosed with early and
      locally advanced breast cancer reporting overall survival by NPI category were
      identified using a systematic literature search. An exploratory meta-analysis was
      conducted to describe survival estimates and assess between-study heterogeneity.
      RESULTS: Twenty-eight studies were identified. Nineteen studies with sufficient
      data on overall survival were included in meta-analysis. A high level of
      heterogeneity in survival estimates was evident with I2 values in the range of 90
      to 98%. CONCLUSIONS: The substantial differences between studies in the
      relationship between NPI categories and survival at 5 and 10 years poses
      challenges for use of this prognostic score in both clinical settings and in
      decision-analytic model-based economic evaluations.

PMID- 30219093
TI  - Monitoring of malaria vectors at the China-Myanmar border while approaching
      malaria elimination.
AB  - BACKGROUND: Tengchong County was one of the counties located at the China-Myanmar
      border with high malaria incidence in the previous decades. As the pilot county
      for malaria elimination at the border area, Tengchong County is aiming to be the
      first county to achieve malaria elimination goal. A cross-sectional entomological
      survey was carried out to evaluate the feasibility of elimination approach and
      assess the receptivity of malaria reintroduction. METHODS: Light traps associated
      with live baits were used to investigate the abundance of adult mosquitoes in
      nine villages in Tengchong County. Light traps were set to collect adult
      mosquitoes in both human houses and cowsheds from dusk till dawn in each site.
      RESULTS: A total of 4948 adult Anopheles mosquitoes were collected from May to
      December in two villages. Of the mosquitoes were captured, 24.2% were in human
      houses and 75.8% in cowsheds. The peak of abundance occurred in July for An.
      sinensis and in September-October for An. minimus (s.l.) Ten Anopheles species
      were collected, the most prevalent being An. sinensis (50.3%), An. peditaeniatus
      (31.6%) and An. minimus (s.l.) (15.8%), contributing to 97.6% of the sample.
      Potential breeding sites were also investigated and a total of 407 larvae were
      collected, with An. sinensis (50.1%) and An. minimus (s.l.) (46.2%) as
      predominant species. Ponds and rice fields were the two preferred breeding sites
      for Anopheles mosquitoes; however, the difference between the number of adults
      and larvae captured suggest other breeding sites might exist. Both An. sinensis
      and An. minimus (s.l.) were found zoophilic with human blood index as 0.21 and
      0.26, respectively. No Plasmodium positive Anopheles specimens were found by PCR
      among 4,000 trapped mosquitoes. CONCLUSIONS: Although no indigenous malaria cases
      have been reported in Tengchong County since 2013, there is still a risk from the
      presence of vectors in the context of human population movements from neighboring
      malaria endemic areas. The presence of An. sinensis, associated to rice fields,
      is particularly worrying. Sustained entomological surveillance is strongly
      suggested even after malaria elimination certification.

PMID- 30219094
TI  - Translating research to policy at the NCSE 2017 symposium "Microbiology of the
      Built Environment: Implications for Health and Design".
AB  - Here, we summarize a symposium entitled "Microbiology of the Built Environment:
      Implications for Health and Design" that was presented at the National Council
      for Science and the Environment (NCSE) 17th National Conference and Global Forum
      in January 2017. We covered topics including indoor microbial exposures and
      childhood asthma, the influence of hospital design on neonatal development, the
      role of the microbiome in our premise (i.e., building) plumbing systems,
      antibiotic resistance, and quantitative microbial risk assessment. This symposium
      engaged the broader scientific and policy communities in a discussion to increase
      awareness of this critical research area and translate findings to practice.

PMID- 30219095
TI  - Umbilical cord tissue cryopreservation: a short review.
AB  - In this review we present current evidence on the possibility of umbilical cord
      tissue cryopreservation for subsequent clinical use. Protocols for obtaining
      umbilical cord-derived vessels, Wharton's jelly-based grafts, multipotent stromal
      cells, and other biomedical products from cryopreserved umbilical cords are
      highlighted, and their prospective clinical applications are discussed.
      Examination of recent literature indicates we should expect high demand for
      cryopreservation of umbilical cord tissues in the near future.

PMID- 30219097
TI  - Polymorphonuclear (PMN) elastase in patients after severe traumatic brain injury.
AB  - BACKGROUND: Data on PNM elastase levels in cerebrospinal fluid following
      traumatic brain injury (TBI) in humans are not available in the literature.
      Therefore, the aim of this prospective study was to evaluate the dynamics of PMN
      elastase in the cerebrospinal fluid (CSF) of patients after TBI. METHODS:
      Patients suffering from isolated, closed TBI, presenting with an initial Glasgow
      coma score <= 8 and with intracerebral hemorrhage on the initial cranial computed
      tomography scan (performed within 90 min after TBI) were enrolled. CSF and blood
      samples were obtained immediately, 12 h, 24 h, 48 h, and 72 h after admission.
      ELISA testing was used to quantify the PMN elastase levels in CSF. In addition,
      the ratio of CSF albumin to serum albumin was calculated to evaluate the role of
      the blood-cerebrospinal fluid barrier (BCSFB). As controls, CSF samples were
      taken from patients receiving spinal anesthesia for elective orthopedic surgery
      of the lower extremity. RESULTS: Twenty-three patients meeting the inclusion
      criteria and ten control patients were enrolled. The PMN elastase showed a
      significant elevation at 48 and 72 h after TBI. When comparing the PMN elastase
      levels of patients with intact BCSFB to patients with defective BCSFB, there was
      no significant difference for the respective observation points. CONCLUSIONS:
      This is the first study to demonstrate that the PMN elastase levels in CSF
      significantly increased in the early posttraumatic phase (48 h and 72 h after
      TBI) in patients. The function of the BCSFB showed no significant influence on
      the PMN levels.

PMID- 30219096
TI  - Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density
      lipoprotein remodeling induced by vitamin C and E combination and their
      beneficial effect on lethal ischemic heart disease in mice.
AB  - BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent
      and its underlying pathogenesis involves dyslipidemia including pro-atherogenic
      high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as
      atheroprotective agents for cardiovascular disease management. However, their
      effects and benefits on high density lipoprotein function and remodeling are
      unknown. In this study, we evaluated the role of vitamin C and E on non HDL
      lipoproteins as well as HDL function and remodeling, along with their effects on
      inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR
      B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks
      before and during atherogenic diet feeding with vitamin C and E added to water
      and diet, respectively. Compared to a control group, combined vitamin C and E
      administration reduced serum total cholesterol and triglyceride levels by
      decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing
      phospholipid as well as increasing PON1 and apo D content, and diminished PLTP
      activity and levels. Vitamin supplementation improved HDL antioxidant function
      and lowered serum TNF-alpha levels. Vitamin C and E combination attenuated
      atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h
      mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid
      metabolism regulating effects, including HDL remodeling and decreased levels of
      apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation
      generated a cardioprotective effect in a murine model of severe and lethal
      atherosclerotic ischemic heart disease.

PMID- 30219098
TI  - Architecture of polymorphisms in the human genome reveals functionally important
      and positively selected variants in immune response and drug transporter genes.
AB  - BACKGROUND: Genetic polymorphisms can contribute to phenotypic differences
      amongst individuals, including disease risk and drug response. Characterization
      of genetic polymorphisms that modulate gene expression and/or protein function
      may facilitate the identification of the causal variants. Here, we present the
      architecture of genetic polymorphisms in the human genome focusing on those
      predicted to be potentially functional/under natural selection and the pathways
      that they reside. RESULTS: In the human genome, polymorphisms that directly
      affect protein sequences and potentially affect function are the most constrained
      variants with the lowest single-nucleotide variant (SNV) density, least
      population differentiation and most significant enrichment of rare alleles. SNVs
      which potentially alter various regulatory sites, e.g. splicing regulatory
      elements, are also generally under negative selection. Interestingly, genes that
      regulate the expression of transcription/splicing factors and histones are
      conserved as a higher proportion of these genes is non-polymorphic, contain ultra
      conserved elements (UCEs) and/or has no non-synonymous SNVs (nsSNVs)/coding
      INDELs. On the other hand, major histocompatibility complex (MHC) genes are the
      most polymorphic with SNVs potentially affecting the binding of
      transcription/splicing factors and microRNAs (miRNA) exhibiting recent positive
      selection (RPS). The drug transporter genes carry the most number of potentially
      deleterious nsSNVs and exhibit signatures of RPS and/or population
      differentiation. These observations suggest that genes that interact with the
      environment are highly polymorphic and targeted by RPS. CONCLUSIONS: In
      conclusion, selective constraints are observed in coding regions, master
      regulator genes, and potentially functional SNVs. In contrast, genes that
      modulate response to the environment are highly polymorphic and under positive
      selection.

PMID- 30219100
TI  - Lean mass mediates the relation between temporal summation of pain and sex in
      young healthy adults.
AB  - BACKGROUND: Previous studies have shown that women experience greater temporal
      summation (TS) of pain than men using a repetitive thermal stimulus. These
      studies, however, did not individualize the thermal stimulus to each subject's
      thermal pain sensitivity. The aim of this study was to investigate sex
      differences in TS using an individualized protocol and potential mediators that
      have been shown to influence TS including physical activity and body composition.
      METHODS: Fifty young healthy men and women (21 men) participated in the study.
      Subjects completed TS testing on the right forearm using a repetitive thermal
      stimulus at a temperature that the subject reported 6/10 pain. Other testing
      included body composition (lunar iDXA), activity monitoring (Actigraph), and Pain
      Catastrophizing Scale (PCS). RESULTS: Women reported greater TS than men (p =
      0.019), and TS was correlated with right arm lean mass (r = - 0.36, p = 0.01) and
      magnification subscale of PCS (r = - 0.32, p = 0.03). Mediation analysis showed a
      complete mediation for the relation between sex and TS by right arm lean mass
      (indirect effect = 2.33, 95% BCa CI [0.42, 4.58]) after controlling for the
      temperature, the magnification subscale of PCS, and the average time spent in
      moderate to vigorous physical activity. CONCLUSION: The results of this study
      suggest that lean mass is a contributing factor to the sex differences in TS.
      Future studies should investigate whether interventions that increase lean mass
      have a positive effect on TS.

PMID- 30219099
TI  - The effects of neuregulin-1beta on intrafusal muscle fiber formation in
      neuromuscular coculture of dorsal root ganglion explants and skeletal muscle
      cells.
AB  - BACKGROUND: The formation of intrafusal muscle (IM) fibers and their contact with
      afferent proprioceptive axons is critical for construction, function, and
      maintenance of the stretch reflex. Many factors affect the formation of IM
      fibers. Finding new factors and mechanisms of IM fiber formation is essential for
      the reconstruction of stretch reflex arc after injury. METHODS: We established a
      coculture system of organotypic dorsal root ganglion (DRG) explants and
      dissociated skeletal muscle (SKM) cells. The formation of IM fibers was observed
      in this coculture system after neuregulin-1beta (NRG-1beta) incubation. RESULTS:
      We found that NRG-1beta promoted outgrowth of neurites and migration of neurons
      from the organotypic DRG explants and that this correlated with an induction of
      growth-associated protein 43 (GAP-43) expression. NRG-1beta also increased the
      amount of nuclear bag fibers and nuclear chain fibers by elevating the proportion
      of tyrosine kinase receptor C (TrkC) phenotypic DRG neurons. In addition, we
      found that the effects of NRG-1beta could be blocked by inhibiting ERK1/2,
      PI3K/Akt, and JAK2/STAT3 signaling pathways. CONCLUSION: These data imply that
      NRG-1beta promoted neurite outgrowth and neuronal migration from the organotypic
      DRG explants and that this correlated with an induction of GAP-43 expression. The
      modulating effects of NRG-1beta on TrkC DRG neuronal phenotype may link to
      promote IM fiber formation. The effects produced by NRG-1beta in this
      neuromuscular coculture system provide new data for the therapeutic potential on
      IM fiber formation after muscle injury.

PMID- 30219102
TI  - Prospective randomized controlled trial in the treatment of lateral epicondylitis
      with a new dynamic wrist orthosis.
AB  - BACKGROUND: In the treatment of lateral epicondylitis (LE), the role of a new
      dynamic wrist orthosis is unclear. PATIENTS AND METHODS: Patients suffering from
      a LE longer than 3 months were multicentrically and prospectively randomized into
      a physiotherapeutic group (PT group) and in a physiotherapy group plus wrist
      orthosis (PT + O group). Physiotherapy consisted of daily eccentric strengthening
      exercises under initial professional supervision. Inclusion criteria were a
      Placzek score greater than 4. Exclusion criteria were previous surgery, rheumatic
      arthritis, elbow instability, radicular symptoms, higher-grade extensor tendon
      rupture, or cervical osteoarthritis. The clinical evaluation was performed after
      12 weeks and 12 months. The Patient-Rated Tennis Elbow Evaluation (PRTEE) scale,
      Placzek Score, the pain rating (VAS), range of motion and the Subjective Elbow
      Score were evaluated. RESULTS: Of the initially 61 patients, 31 were followed up
      after 12 weeks and 22 after 12 months. Twenty-nine patients (43%) were male, the
      mean age was 46, and 44 patients (66%) had the right elbow involved. At 12 weeks,
      there was a pain reduction on the VAS in both groups (PT + O: 6.5-3.7 [p = .001];
      PT: 4.7-4.1 [p = .468]), albeit it was only significant for the PT + O group. At
      12 months, reduction was significant in both groups (PT + O: 1.1 [p = .000]; PT:
      1.3 [p = .000]). The painless maximum hand strength in kg improved in both groups
      significant after 3 and 12 months. The Placzek score was reduced from 8.25 to 3.5
      [p = .001] after 12 weeks for the PT + O group and from 8.1 to 3.8 [p = .000] in
      the PT group, as well as after 12 months in the PT + O group to 0 [p = .000] and
      in the PT group to 2.0 [p = .000]. The PRTEE improved in both groups after 12
      weeks (PT + O: 52.8--31.3 [p = .002]; PT: 48.6-37.6 [p = .185]) and 12 months (PT
      + O: 16.15 [p = .000]; PT: 16.6 [p = .000]), although the reduction at 12 weeks
      was not significant for the PT group. CONCLUSION: The elbow orthosis appears to
      accelerate the healing process with respect to the PRTEE and pain on the VAS (12
      weeks follow-up), although there is an adjustment after 12 months in both groups
      and a significant improvement of symptoms is achieved in all endpoints.

PMID- 30219101
TI  - DSCAM differentially modulates pre- and postsynaptic structural and functional
      central connectivity during visual system wiring.
AB  - BACKGROUND: Proper patterning of dendritic and axonal arbors is a critical step
      in the formation of functional neuronal circuits. Developing circuits rely on an
      array of molecular cues to shape arbor morphology, but the underlying mechanisms
      guiding the structural formation and interconnectivity of pre- and postsynaptic
      arbors in real time remain unclear. Here we explore how Down syndrome cell
      adhesion molecule (DSCAM) differentially shapes the dendritic morphology of
      central neurons and their presynaptic retinal ganglion cell (RGC) axons in the
      developing vertebrate visual system. METHODS: The cell-autonomous role of DSCAM,
      in tectal neurons and in RGCs, was examined using targeted single-cell knockdown
      and overexpression approaches in developing Xenopus laevis tadpoles. Axonal
      arbors of RGCs and dendritic arbors of tectal neurons were visualized using real
      time in vivo confocal microscopy imaging over the course of 3 days. RESULTS: In
      the Xenopus visual system, DSCAM immunoreactivity is present in RGCs, cells in
      the optic tectum and the tectal neuropil at the time retinotectal synaptic
      connections are made. Downregulating DSCAM in tectal neurons significantly
      increased dendritic growth and branching rates while inducing dendrites to take
      on tortuous paths. Overexpression of DSCAM, in contrast, reduced dendritic
      branching and growth rate. Functional deficits mediated by tectal DSCAM knockdown
      were examined using visually guided behavioral assays in swimming tadpoles,
      revealing irregular behavioral responses to visual stimulus. Functional deficits
      in visual behavior also corresponded with changes in VGLUT/VGAT expression,
      markers of excitatory and inhibitory transmission, in the tectum. Conversely,
      single-cell DSCAM knockdown in the retina revealed that RGC axon arborization at
      the target is influenced by DSCAM, where axons grew at a slower rate and remained
      relatively simple. In the retina, dendritic arbors of RGCs were not affected by
      the reduction of DSCAM expression. CONCLUSIONS: Together, our observations
      implicate DSCAM in the control of both pre- and postsynaptic structural and
      functional connectivity in the developing retinotectal circuit, where it
      primarily acts as a neuronal brake to limit and guide postsynaptic dendrite
      growth of tectal neurons while it also facilitates arborization of presynaptic
      RGC axons cell autonomously.

PMID- 30219103
TI  - MetaWRAP-a flexible pipeline for genome-resolved metagenomic data analysis.
AB  - BACKGROUND: The study of microbiomes using whole-metagenome shotgun sequencing
      enables the analysis of uncultivated microbial populations that may have
      important roles in their environments. Extracting individual draft genomes (bins)
      facilitates metagenomic analysis at the single genome level. Software and
      pipelines for such analysis have become diverse and sophisticated, resulting in a
      significant burden for biologists to access and use them. Furthermore, while bin
      extraction algorithms are rapidly improving, there is still a lack of tools for
      their evaluation and visualization. RESULTS: To address these challenges, we
      present metaWRAP, a modular pipeline software for shotgun metagenomic data
      analysis. MetaWRAP deploys state-of-the-art software to handle metagenomic data
      processing starting from raw sequencing reads and ending in metagenomic bins and
      their analysis. MetaWRAP is flexible enough to give investigators control over
      the analysis, while still being easy-to-install and easy-to-use. It includes
      hybrid algorithms that leverage the strengths of a variety of software to extract
      and refine high-quality bins from metagenomic data through bin consolidation and
      reassembly. MetaWRAP's hybrid bin extraction algorithm outperforms individual
      binning approaches and other bin consolidation programs in both synthetic and
      real data sets. Finally, metaWRAP comes with numerous modules for the analysis of
      metagenomic bins, including taxonomy assignment, abundance estimation, functional
      annotation, and visualization. CONCLUSIONS: MetaWRAP is an easy-to-use modular
      pipeline that automates the core tasks in metagenomic analysis, while
      contributing significant improvements to the extraction and interpretation of
      high-quality metagenomic bins. The bin refinement and reassembly modules of
      metaWRAP consistently outperform other binning approaches. Each module of
      metaWRAP is also a standalone component, making it a flexible and versatile tool
      for tackling metagenomic shotgun sequencing data. MetaWRAP is open-source
      software available at https://github.com/bxlab/metaWRAP .

PMID- 30219104
TI  - Longitudinal development of the dust microbiome in a newly opened Norwegian
      kindergarten.
AB  - BACKGROUND: In Norway, 91% of children aged 1-5 attend kindergarten where they
      are exposed to indoor microbiomes which can have relevance for development and
      health. In order to gain a better understanding of the composition of the indoor
      microbiome and how it is affected by occupancy over time, floor dust samples from
      a newly opened kindergarten were investigated. Samples were collected during an
      11-month period. Samples were analyzed for bacterial composition using 16S rRNA
      gene sequencing. Samples were also screened for four clinically relevant
      antibiotic resistance genes. In addition, Petrifilm analyses were used to
      evaluate surface hygiene. RESULTS: Significant changes in the microbial community
      composition were observed over time (PERMANOVA, P < 0.05). Particularly, changes
      in the abundance and the proportions of human associated bacteria were found. A
      decrease in the prevalence of Propionibacterium from over 16% abundance to less
      than 1% and an increase in Streptococcus from 10 to 16% were the most significant
      findings. Four classes of clinically relevant antibiotic resistance genes were
      tested for; three were detected in the dust, indicating the presence of resistant
      bacteria and a potential for resistance spread. Petrifilm analysis showed that
      some surfaces in the kindergarten were of consistent poor hygienic quality, and
      new hygienic routines are required. CONCLUSIONS: This study, which is the first
      of its kind performed at a newly opened kindergarten, reveals changes in the
      microbiome over time as well as the presence of antibiotic resistance genes and
      hygiene issues which are of relevance for occupant health.

PMID- 30219105
TI  - Factors associated with extrajudicial arrest for syringe possession: results of a
      department-wide survey of municipal police in Tijuana, Mexico.
AB  - BACKGROUND: Mexican law permits syringe purchase and possession without
      prescription. Nonetheless, people who inject drugs (PWID) frequently report
      arrest for syringe possession. Extrajudicial arrests not only violate human
      rights, but also significantly increase the risk of blood-borne infection
      transmission and other health harms among PWID and police personnel. To better
      understand how police practices contribute to the PWID risk environment, prior
      research has primarily examined drug user perspectives and experiences. This
      study focuses on municipal police officers (MPOs) in Tijuana, Mexico to identify
      factors associated with self-reported arrests for syringe possession. METHODS:
      Participants were active police officers aged >=18 years, who completed a self
      administered questionnaire on knowledge, attitudes and behaviors related to
      occupational safety, drug laws, and harm reduction strategies. Univariable and
      multivariable logistic regression was used to identify correlates of recent
      syringe possession arrest. RESULTS: Among 1044 MPOs, nearly half (47.9%) reported
      always/sometimes making arrests for syringe possession (previous 6mo). Factors
      independently associated with more frequent arrest included being male (Adjusted
      Odds Ratio [AOR] = 1.62; 95% Confidence Interval [95% CI] =1.04-2.52; working in
      a district along Tijuana River Canal (where PWID congregate) (AOR = 2.85; 95%CI =
      2.16-3.77); having recently experienced a physical altercation with PWID (AOR =
      2.83; 95% CI = 2.15-3.74); and having recently referred PWID to social and health
      services (AOR = 1.97; 95% CI = 1.48-2.61). Conversely, odds were significantly
      lower among officers reporting knowing that syringe possession is legal (AOR =
      0.61; 95% CI = 0.46-0.82). CONCLUSIONS: Police and related criminal justice
      stakeholders (e.g., municipal judges, prosecutors) play a key role in shaping
      PWID risk environment. Findings highlight the urgent need for structural
      interventions to reduce extra-judicial syringe possession arrests. Police
      training, increasing gender and other forms of diversity, and policy reforms at
      various governmental and institutional levels are necessary to reduce police
      occupational risks, improve knowledge of drug laws, and facilitate harm reduction
      strategies that promote human rights and community health.

PMID- 30219107
TI  - Sustaining knowledge translation interventions for chronic disease management in
      older adults: protocol for a systematic review and network meta-analysis.
AB  - BACKGROUND: Failure to sustain knowledge translation (KT) interventions impacts
      patients and health systems, diminishing confidence in future implementation.
      Sustaining KT interventions used to implement chronic disease management (CDM)
      interventions is of critical importance given the proportion of older adults with
      chronic diseases and their need for ongoing care. Our objectives are to (1)
      complete a systematic review and network meta-analysis of the effectiveness and
      cost-effectiveness of sustainability of KT interventions that target CDM for end
      users including older patients, clinicians, public health officials, health
      services managers and policy-makers on health care outcomes beyond 1 year after
      implementation or the termination of initial project funding and (2) use the
      results of this review to complete an economic analysis of the interventions
      identified to be effective. METHODS: For objective 1, comprehensive searches of
      relevant electronic databases (e.g. MEDLINE, EMBASE, Cochrane Central Register of
      Controlled Trials), websites of health care provider organisations and funding
      agencies will be conducted. We will include randomised controlled trials (RCTs)
      examining the impact of a KT intervention targeting CDM in adults aged 65 years
      and older. To examine cost, economic studies (e.g. cost, cost-effectiveness
      analyses) will be included. Our primary outcome will be the sustainability of the
      delivery of the KT intervention beyond 1 year after implementation or termination
      of study funding. Secondary outcomes will include behaviour changes at the level
      of the patient (e.g. symptom management) and clinician (e.g. physician test
      ordering) and health system (e.g. cost, hospital admissions). Article screening,
      data abstraction and risk of bias assessment will be completed independently by
      two reviewers. Using established methods, if the assumption of transitivity is
      valid and the evidence forms a connected network, Bayesian random-effects
      pairwise and network meta-analysis will be conducted. For objective 2, we will
      build a decision analytic model comparing effective interventions to estimate an
      incremental cost-effectiveness ratio. DISCUSSION: Our results will inform
      knowledge users (e.g. patients, clinicians, policy-makers) regarding the
      sustainability of KT interventions for CDM. Dissemination plan of our results
      will be tailored to end-users and include passive (e.g. publications, website
      posting) and interactive (e.g. knowledge exchange events with stakeholders)
      strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

PMID- 30219106
TI  - What information and the extent of information research participants need in
      informed consent forms: a multi-country survey.
AB  - BACKGROUND: The use of lengthy, detailed, and complex informed consent forms
      (ICFs) is of paramount concern in biomedical research as it may not truly promote
      the rights and interests of research participants. The extent of information in
      ICFs has been the subject of debates for decades; however, no clear guidance is
      given. Thus, the objective of this study was to determine the perspectives of
      research participants about the type and extent of information they need when
      they are invited to participate in biomedical research. METHODS: This multi
      center, cross-sectional, descriptive survey was conducted at 54 study sites in
      seven Asia-Pacific countries. A modified Likert-scale questionnaire was used to
      determine the importance of each element in the ICF among research participants
      of a biomedical study, with an anchored rating scale from 1 (not important) to 5
      (very important). RESULTS: Of the 2484 questionnaires distributed, 2113 (85.1%)
      were returned. The majority of respondents considered most elements required in
      the ICF to be 'moderately important' to 'very important' for their decision
      making (mean score, ranging from 3.58 to 4.47). Major foreseeable risk, direct
      benefit, and common adverse effects of the intervention were considered to be of
      most concerned elements in the ICF (mean score = 4.47, 4.47, and 4.45,
      respectively). CONCLUSIONS: Research participants would like to be informed of
      the ICF elements required by ethical guidelines and regulations; however, the
      importance of each element varied, e.g., risk and benefit associated with
      research participants were considered to be more important than the general
      nature or technical details of research. Using a participant-oriented approach by
      providing more details of the participant-interested elements while avoiding
      unnecessarily lengthy details of other less important elements would enhance the
      quality of the ICF.

PMID- 30219108
TI  - Molecular analysis of Pseudomonas aeruginosa isolated from clinical,
      environmental and cockroach sources by ERIC-PCR.
AB  - OBJECTIVE: The objective of this study was to investigate the antibiotic
      susceptibility, virulence factors and clonal relationship among Pseudomonas
      aeruginosa isolated from environmental sources, hospitalized patients and the
      surfaces of cockroaches in the ICUs of four hospitals in Hamadan, west of Iran. A
      total of 237, 286 and 156 bacterial isolates were collected from clinical,
      environmental and cockroach sources respectively from May to September, 2017. The
      antimicrobial susceptibility was determined using disk diffusion method. The
      virulence factors, exotoxins A, S and U were detected by PCR. The genetic linkage
      of P. aeruginosa isolates were analyzed by Enterobacterial Repetitive Intergenic
      Consensus (ERIC)-PCR. RESULTS: According to our findings, 58 (24.4%), 46 (16%)
      and 5 (3.25) P. aeruginosa were isolated from clinical, environmental and
      cockroach samples respectively. The MDR phenotypes were detected in 18 (45%) and
      15 (37.5%) of clinical and environmental strains. The environmental isolates
      harbored more exoA and exoS than did clinical isolates. Genetic diversity was
      established among P. aeruginosa isolates as 14 different ERIC fingerprints were
      detected. The clonal relationships was detected among clinical, environmental and
      cockroach isolates. Our results highlighted the importance of identifying and
      controlling the potential sources of P. aeruginosa infections in hospitals.

PMID- 30219111
TI  - The AsMA Global Connection Story with EASA.

PMID- 30219112
TI  - Spatial Orientation and Directional Judgments in Pilots vs. Nonpilots.
AB  - BACKGROUND: Reading a map requires the ability to judge one's position in a large
      scale space from information presented in a small-scale representation.
      Individuals are more accurate and faster in making judgments when the "up"
      direction on the map is the same as the "forward" direction of the environment,
      which is when a map is aligned with the perspective of the spatial layout they
      have learned (alignment effect). The aim of this study was to explore whether
      military pilots, who have high spatial abilities, would not show the alignment
      effect compared with nonpilots. METHODS: Recruited were 20 military pilots and 20
      nonpilots. Mean flight hours were 418.75. Nonpilots without flight experience
      were matched for age and education with pilots. Subjects were asked to learn a
      map and to perform directional judgments to verify whether the alignment effect
      was present considering absolute angular errors. RESULTS: An ANOVA for mixed
      designs on absolute angular errors revealed a main "group" effect: pilots
      performed better than nonpilots (pilots: M = 22.60 +/- 5.57; nonpilots: M = 82.59
      +/- 5.56). A main "directional judgments" effect was also observed: aligned
      judgements were easier than contra-aligned judgements (aligned, M = 9.277 +/-
      0.938; contra-aligned, M = 11.004 +/- 0.805). ANOVA showed a significant "group *
      directional judgments" interaction: post hoc comparison showed that contra
      aligned were more difficult than aligned judgments for nonpilots. DISCUSSION:
      High visuo-spatial abilities preserved pilots from having alignment effect bias.
      They performed directional judgments equally well, being less influenced by the
      increased cognitive effort requested by the changing perspective.Verde P,
      Angelino G, Piccolo F, Carrozzo P, Bottiglieri A, Lugli L, Piccardi L, Nori R.
      Spatial orientation and directional judgments in pilots vs. nonpilots. Aerosp Med
      Hum Perform. 2018; 89(10):857-862.

PMID- 30219113
TI  - Change Detection Flicker Task Effects on Simulator-Induced Spatial Disorientation
      Events.
AB  - INTRODUCTION: A visual stimulus change detection is an extremely important
      pilot's cognitive process. This is especially true when pilot errors caused by
      perceptual failures have a negative effect on his/her spatial orientation. The
      aim of this research was to investigate the effect of the change detection
      flicker task (CDFT) on pilots' response to spatial disorientation (SD) events. We
      hypothesized that the additional cognitive processing, based on CDFT, produces
      more deterioration of the pilots' spatial orientation. METHODS: Using an SD
      flight simulator, 50 male military pilots (M = 27.2; SD = 6.68) were exposed to
      12 flight sequences. Of the 12 flight profiles, 6 involved an SD conflict, with 3
      involving motion illusions and 3 with visual illusions. We measured and compared
      pilots' flight performance in response to visual and motion illusion conflicts
      across two simulations (CDFT vs. control) and SD conditions (nonconflict vs.
      conflict). RESULTS: Of the six applied illusions, significant differences in
      pilot flight performance were found for three visual and one vestibular illusion
      (Coriolis). The differences were observed between control and CDFT groups for
      both nonconflict and conflict flight sequences, associated with the approach and
      landing maneuvers. DISCUSSION: The CDFT increased the pilots' cognitive workload,
      affecting their flight performance and susceptibility to SD, especially in the
      approach and landing maneuvers. This partially supports our hypothesis that
      performing the CDFT leads to greater deterioration of pilots' spatial
      orientation. We recommend that when problems in maintaining proper flight
      performance arise, pilots should not respond to external stimuli until they have
      recovered their spatial orientation.Lewkowicz R, Fudali-Czyz A, Balaj B, Francuz
      P. Change detection flicker task effects on simulator-induced spatial
      disorientation events. Aerosp Med Hum Perform. 2018; 89(10):863-872.

PMID- 30219114
TI  - Spatial Disorientation Influences on Pilots' Visual Scanning and Flight
      Performance.
AB  - BACKGROUND: Adequate instrument scanning is considered an important
      countermeasure against spatial disorientation (SD). Remarkably, literature on the
      relation between SD and pilots' visual scanning is scarce. The objective of this
      simulator study was to investigate the influence of SD on pilots' visual scanning
      and flight performance. METHODS: In a ground-based SD simulator, 10 novice
      military pilots were asked to manually fly 3 circuits. Unknowingly to the pilots,
      the final circuit contained one visual and four vestibular SD events. Simulator
      motion, flight performance, pilots' gaze direction, and control inputs were
      recorded and analyzed. Afterwards the pilots filled in a questionnaire about
      their recognition of events. RESULTS: Three of the five SD events significantly
      affected pilots' flight performance and gaze behavior. First, the false horizon
      during the cloud leans induced an unintended roll rate, 0.41 +/- 0.36 degrees  .
      s-1, when the pilots were looking out the window. Second, the Coriolis illusion
      caused a 0.44 +/- 0.18 s delay in the first glance to the attitude indicator and
      triggered an unintended roll rate, 1.25 +/- 1.33 degrees  . s-1, and bank angle
      deviation of 3.4 +/- 3.7 degrees  during the coordinated turn. Third, the
      somatogravic illusion affected pilots' pitch inputs on the stick, but this seems
      to be confounded by inaccurate simulation of the illusion. DISCUSSION: This study
      provides direct experimental evidence that SD can evoke inappropriate control
      inputs and can influence the pilots' scanning behavior, even when SD is not
      recognized. We conclude that gaze tracking provides useful feedback on the
      pilot's instrument scan during SD simulator training when using appropriate
      scenarios and simulator motion.Ledegang WD, Groen EL. Spatial disorientation
      influences on pilots' visual scanning and flight performance. Aerosp Med Hum
      Perform. 2018; 89(10):873-882.

PMID- 30219115
TI  - Chinese Herbal Medicine Effects on Muscle Atrophy Induced by Simulated
      Microgravity.
AB  - BACKGROUND: Skeletal muscle atrophy is a striking example of the multiple changes
      in the physiological state of humans and animals induced by microgravity.
      Previous studies have shown that a blood circulation disorder may be a cause of
      this atrophy, and traditional Chinese medicine has been regarded as a potential
      countermeasure to reverse the atrophy in China. This study was carried out to
      test the effects of Xuefuzhuyu capsules (XFZY) on the skeletal muscle atrophy
      induced by simulated microgravity. METHODS: The mass and cross-sectional area of
      the soleus muscle were compared in rats treated with XFZY that were hindlimb
      unloaded for 30 d (XFZY-TS group), untreated rats that were hindlimb unloaded for
      30 d (TS group), and control rats (CON group). The expression and phosphorylation
      levels of key proteins of the sarcoplasmic reticulum stress system were also
      measured. RESULTS: Treatment with XFZY attenuated the loss of muscle mass and
      cross-sectional area induced by hindlimb unloading. Western blot analysis showed
      that the phosphatidyl-inositol-3-kinase/phospho-Akt (PI3K/p-Akt) pathways were
      down-regulated after 30 d in the TS group compared with the CON group. This
      effect was partly reversed by XFZY. Hindlimb unloading increased the expression
      of glucose-regulated protein 78 (GRP78), cytosine-cytosine-adenosine-adenosine
      thymidine/enhancer-binding protein homologous protein (CHOP), C-Jun N-terminal
      kinase (JNK), and Caspase 12. Treatment with XFZY alleviated this increased
      protein expression. DISCUSSION: Our results suggest that XFZY could partially
      reverse the effects of hindlimb unloading on muscle atrophy and perhaps target
      the sarcoplasmic reticulum stress system, possibly through the GRP78-CHOP-JNK
      Caspase 12 pathway.Zhang S, Yuan M, Cheng C, Xia D, Wu S. Chinese herbal medicine
      effects on muscle atrophy induced by simulated microgravity. Aerosp Med Hum
      Perform. 2018; 89(10):883-888.

PMID- 30219116
TI  - Monitoring the Effectiveness of Fatigue Risk Management: A Survey of Pilots'
      Concerns.
AB  - INTRODUCTION: Airlines are required to monitor the effectiveness of their pilot
      fatigue risk management. The present survey sought the views of all pilots at
      Delta Air Lines on fatigue-related issues raised by their colleagues
      participating in regular airline safety audits. METHODS: All 13,217 pilots from 9
      aircraft fleets were invited to participate in an anonymous online survey.
      Questions related to aspects of scheduling, fatigue mitigations, and fatigue
      safety culture. RESULTS: There were 1108 pilots who completed the survey
      (response rate = 8.4%). On 7/9 fleets, most pilots thought 5- to 7-d rotations
      were too long (exceptions: B747, median = 14 d; A330 median = 8.5 d). In the
      previous year, on average across all fleets, 60.6% of pilots had worked up to or
      beyond their personal rotation limit (minimum, B747 = 6.3%; maximum, MD88/90 =
      75.9%). Rotations where duty periods start progressively earlier were considered
      highly fatiguing by 73.8% of pilots, compared to 14.7% for rotations where duty
      periods started progressively later and 1.6% for rotations with successive duty
      periods starting at the same time. The median optimum break length between
      rotations was 3-4 d. On 7/9 fleets, fewer than 20% of pilots tried to build their
      monthly schedules with back-to-back rotations (exceptions: B747, 43.8%; A330,
      34.3%). Awareness of fatigue and perceptions of company fatigue risk management
      activities varied widely among fleets. DISCUSSION: The findings identify possible
      improvements in fatigue risk management and highlight that care is needed when
      extrapolating from one operational context to another. As a safety assurance
      exercise, we recommend repeating the survey biannually, or sooner if warranted by
      specific circumstances.Gander P, Mangie J, Phillips A, Santos-Fernandez E, Wu LJ.
      Monitoring the effectiveness of fatigue risk management: a survey of pilots'
      concerns. Aerosp Med Hum Perform. 2018; 89(10):889-895.

PMID- 30219109
TI  - Live imaging of developing mouse retinal slices.
AB  - BACKGROUND: Ex vivo, whole-mount explant culture of the rodent retina has proved
      to be a valuable approach for studying retinal development. In a limited number
      of recent studies, this method has been coupled to live fluorescent microscopy
      with the goal of directly observing dynamic cellular events. However, retinal
      tissue thickness imposes significant technical limitations. To obtain 3
      dimensional images with high quality axial resolution, investigators are
      restricted to specific areas of the retina and require microscopes, such as 2
      photon, with a higher level of depth penetrance. Here, we report a retinal live
      imaging method that is more amenable to a wider array of imaging systems and does
      not compromise resolution of retinal cross-sectional area. RESULTS: Mouse retinal
      slice cultures were prepared and standard, inverted confocal microscopy was used
      to generate movies with high quality resolution of retinal cross-sections. To
      illustrate the ability of this method to capture discrete, physiologically
      relevant events during retinal development, we imaged the dynamics of the Fucci
      cell cycle reporter in both wild type and Cyclin D1 mutant retinal progenitor
      cells (RPCs) undergoing interkinetic nuclear migration (INM). Like previously
      reported for the zebrafish, mouse RPCs in G1 phase migrated stochastically and
      exhibited overall basal drift during development. In contrast, mouse RPCs in G2
      phase displayed directed, apical migration toward the ventricular zone prior to
      mitosis. We also determined that Cyclin D1 knockout RPCs in G2 exhibited a slower
      apical velocity as compared to wild type. These data are consistent with previous
      IdU/BrdU window labeling experiments on Cyclin D1 knockout RPCs indicating an
      elongated cell cycle. Finally, to illustrate the ability to monitor retinal
      neuron differentiation, we imaged early postnatal horizontal cells (HCs). Time
      lapse movies uncovered specific HC neurite dynamics consistent with previously
      published data showing an instructive role for transient vertical neurites in HC
      mosaic formation. CONCLUSIONS: We have detailed a straightforward method to image
      mouse retinal slice culture preparations that, due to its relative ease, extends
      live retinal imaging capabilities to a more diverse group of scientists. We have
      also shown that, by using a slice technique, we can achieve excellent lateral
      resolution, which is advantageous for capturing intracellular dynamics and
      overall cell movements during retinal development and differentiation.

PMID- 30219117
TI  - Content Validity of Level Two of the Royal Air Force Aircrew Conditioning
      Programme.
AB  - INTRODUCTION: The prevalence of flight-related neck pain in all Royal Air Force
      (RAF) aircrew is 66% and 70% in UK fast-jet aircrew. The RAF Aircrew Conditioning
      Programme (ACP) has been designed to enhance pilot performance through reducing
      fatigue and strain injuries, particularly to the neck. Content validity of the
      ACP was assessed to determine the appropriateness for delivery to aircrew.
      METHODS: Six international medical experts reviewed level two of the ACP, which
      is delivered to student aircrew who have completed basic instruction in cervical
      spine stability, core stability and initial technique instruction for strength
      training. Content validity on overall exercise approach (5 items) and specific
      exercise session (24 items) was rated on a 4-point Likert-type ordinal scale for
      Relevance and Simplicity. Four reviewers had experience of delivering an exercise
      program to aircrew. The item-content validity index (I-CVI) was the proportion of
      experts rating an item/exercise as acceptable (score 3-4) while protocol-CVI was
      the average I-CVI across items. RESULTS: Of the suggested exercise sessions, 20
      reached an excellent I-CVI (1.00) for Relevance (4 reached acceptable I-CVI
      (0.83)), and 21 reached an excellent I-CVI (1.00) for Simplicity (3 reached
      acceptable I-CVI (0.83)). Protocol-CVI for the ACP was excellent for Relevance
      (0.90) and good for Simplicity (0.83). The need for sufficient supervision during
      the exercises was recommended for safe exercise execution and to maintain
      adherence. CONCLUSION: The ACP demonstrated excellent relevance for the target
      population. The aircrew require additional supervision with the more complex neck
      exercises to enhance simplicity with the ACP.Slungaard E, Green NDC, Newham DJ,
      Harridge SDR. Content validity of level two of the Royal Air Force Aircrew
      Conditioning Program. Aerosp Med Hum Perform. 2018; 89(10):896-904.

PMID- 30219118
TI  - The U.S. Experience with Special Issuance Waivers.
AB  - INTRODUCTION: The special issuance (SI) waiver is the primary mechanism for U.S.
      pilots who do not meet FAA standards to obtain a medical certificate. About
      34,000 pilots possess an SI waiver, but there is a large gap in knowledge of the
      relationship of SI waivers to aviation safety. METHODS: All FAA pilot medical
      exams from 2002 through 2011 were matched to the National Transportation Safety
      Board accident database. The association of an SI waiver with accidents was
      explored using logistic regression models. Accident rates were also calculated
      using a novel technique based on pilots' reported flight times on their
      applications for medical certification. RESULTS: For third-class flight exams
      overall, the presence of an SI waiver is associated with 8.7% lower odds of an
      accident than regular issuance exams. The calculated overall accident rate was
      6.6 per 100,000 h. For the first and second-class exams, there was no significant
      association of SI waivers with safety for the overall group. The oldest and
      youngest pilots in the third-class group and the younger pilots in the first and
      second-class groups had somewhat elevated accident odds. The significance of
      these higher odds is uncertain, especially for the younger pilots who have a
      probable flight time bias. DISCUSSION: The overall FAA program of special
      issuance waivers shows no detrimental effect on aviation accidents and enables a
      large number of pilots to safely continue their aviation pursuits in spite of
      failure to meet specific regulatory medical standards.Mills WD, Davis JT. The
      U.S. experience with special issuance waivers. Aerosp Med Hum Perform. 2018;
      89(10):905-911.

PMID- 30219119
TI  - Aeromedical Certification Following Mechanical Aortic and Mitral Valve Implants
      in the United Kingdom.
AB  - BACKGROUND: For many years, anticoagulant therapy had been deemed unacceptable
      for civilian pilot medical certification in the United Kingdom under the Joint
      Aviation Authorities Requirements and, therefore, mechanical valve implants were
      disqualifying. In 2012, this restriction was removed by implementation of the
      European Union requirements. This study was undertaken to assess the medical
      evidence available to develop a certificatory policy following mechanical valve
      implants in the United Kingdom. METHODS: A literature review was performed for
      complication rates following the implantation of mechanical aortic and mitral
      valves. This study was confined to the three major types of valve commonly used
      in current clinical practice: the ATS, the Carbomedics, and the St. Jude Medical
      valves. RESULTS: We identified 28 papers on aortic valve replacements and 22
      papers on mitral valve replacements. Data were extracted for the late
      complication rates for endocarditis, paravalvular leak, thromboembolism,
      hemorrhage, and structural valve dysfunction. The total calculated incidence of a
      late complication was 3.8% per annum for aortic valves over a mean follow-up
      period of 57 mo and 5.2% per annum for mitral valves over a mean follow-up period
      of 61 mo. Both of these exceed the maximum 1% per annum medical incapacitation
      risk considered acceptable for professional multicrew pilot operations.
      CONCLUSION: Confounders and sources of error in estimating the risks and methods
      to mitigate these are considered. A certificatory policy is proposed and the UK
      experience of mechanical valve replacements is described.Jagathesan T, O'Nunain
      S, O'Brien M. Aeromedical certification following mechanical aortic and mitral
      valve implants in the United Kingdom. Aerosp Med Hum Perform. 2018; 89(10):912
      917.

PMID- 30219120
TI  - Thermal Regulation of Emergency Oxygen Supplies in Commercial Space Vehicles.
AB  - INTRODUCTION: While NASA requires that commercial spaceflight vehicles provide
      onboard emergency oxygen supplies for crew, there are currently no requirements
      in place regarding thermal constraints of delivered gas. The question has been
      raised whether or not onboard emergency oxygen supplies must be warmed prior to
      administration to the crew, as inclusion of warming capabilities will increase
      the complexity and mass of life support systems in the vehicle. We sought to
      identify the risk of various inhaled oxygen temperatures and resultant pulmonary
      inflammatory response in potentially injured crewmembers. METHODS: A systematic
      review of published literature was conducted concerning thermal regulation of
      inhaled gases, reactive airway response, and inflammatory reactions. In
      particular, we sought literature that correlated inhaled gas temperature to
      airway response to identify a temperature threshold that would avoid deleterious
      sequelae. RESULTS: Cold air inhalation can induce acute bronchoconstriction,
      increased respiratory rate, and associated dyspnea and hypoxia. Physiological
      response to cold air varies between healthy lungs and injured tissues, and
      increased inflammation is associated with increasing airway reactivity. Most
      studies suggest that inhaled gas temperatures below 10 degrees C may induce
      deleterious physiological sequelae. DISCUSSION: Best practices would include
      maintenance of inhaled gas temperatures to >10 degrees C to avoid poor
      physiological response, preferably as close to physiological norms as possible.
      Given that inhaled gas temperature may be altered by transit through an oxygen
      delivery system, measurement of actual delivered gas temperature should occur at
      the point of crewmember inhalation.Pattarini JM, Blue RS, Alexander DJ. Thermal
      regulation of emergency oxygen supplies in commercial space vehicles. Aerosp Med
      Hum Perform. 2018; 89(10):918-922.

PMID- 30219121
TI  - Semicircular Canal Dehiscence Syndrome and Vestibular Dysfunction Disqualify a
      Military Student Pilot.
AB  - BACKGROUND: Humans detect motion and gravity via the labyrinthine system of the
      inner ear, which consists of the vestibule and the semicircular canals. The
      vestibular system provides three major functions for maintaining balance and
      orientation. First, it maximizes the effectiveness of the visual system. Second,
      it provides orientational information necessary for performing both skilled and
      reflexive motor activities. Third, in the absence of vision, the vestibular
      system provides a reasonably accurate perception of motion and position. Although
      these organs provide important cues for basic orientation on the ground, they
      often provide misleading information during flight. A superior semicircular canal
      dehiscence can cause an individual to experience disorientation and vertigo-like
      symptoms. CASE REPORT: A 30-yr-old male student pilot experienced airsickness on
      his first several flights in the T-6A Texan II aircraft. Airsickness is common
      among student pilots in the early stages of flight training; however, the subject
      pilot's symptoms lasted well beyond the normal 24 h, and included vertiginous
      symptoms lasting days after his last flight. His persistent symptoms required he
      be held out of training for further evaluation. Comprehensive vestibular and
      audiological testing were normal; however, a CT scan of the temporal bones showed
      a left superior semicircular canal dehiscence, and he was diagnosed with left
      labyrinthine fistula as the cause of his vertigo. He was medically eliminated
      from pilot training and permanently disqualified from U.S. Air Force flying
      duties. DISCUSSION: Spatial disorientation remains one of the deadliest factors
      related to aircraft mishaps every year. In this case, an abnormal presentation of
      airsickness that prompted further evaluation may have prevented a dangerous
      situation in the air. In standard airsickness, the goal is to keep the pilot
      flying to expedite adaptation, so this case highlights the importance of
      distinguishing between normal airsickness and a spatially disorienting medical
      condition.Dreibelbis JA, Organ BE. Semicircular canal dehiscence syndrome and
      vestibular dysfunction disqualify a military student pilot. Aerosp Med Hum
      Perform. 2018; 89(10):923-926.

PMID- 30219123
TI  - Letter to the Editor re: The Persistent Issue of Simulator Sickness in Naval
      Aviation Training: Letter.

PMID- 30219122
TI  - Bone Conduction as a Viable Alternative to Current Communications Systems in
      Fighter Cockpits.
AB  - INTRODUCTION: Effective voice communication is essential when operating aircraft.
      Because of the loud operating environment in fighter cockpits, it has been a
      challenge to provide effective communication while simultaneously protecting the
      hearing sense. The objective of this study was to determine the feasibility of
      using bone conducting transducers (BCT) in place of legacy communications systems
      in fighter cockpits. METHODS: A military flight helmet was modified and outfitted
      with BCT and air-conducting speakers. BCT were independently tested against air
      conducting speakers using a clinical audiometer under three conditions: without
      earplugs, with earplugs, and with earplugs in the presence of 100-dB broad
      spectrum noise. Three test subjects were given an audiological examination using
      tones of varying intensity ranging from 100 Hz to 8000 Hz. The lowest hearable
      intensity indicated by button press was recorded for each frequency. RESULTS: In
      the presence of 100-dB ambient noise, bone conducting transducers performed
      better than air-conducting speakers at all frequencies. Hearability of BCT by
      audiogram was, on average, 10-20% lower intensity (dB) than air-conducting
      speakers. DISCUSSION: Currently, USAF pilots wear two layers of hearing
      protection; i.e., the helmet's integrated earcup and some form of ear plug (e.g.,
      foam earplug or custom-molded earbud). Our results suggest that bone conducting
      audio transducers may be better for layered hearing protection than air
      conducting speakers when used with foam earplugs. Given the cost, complexity, and
      non-interoperability of custom-molded earphones, helmet-integrated bone
      conducting transducers and foam earplugs may be a better option for sustained
      airborne operations.Bradke BS, White Z, Poston J. Bone conduction as a viable
      alternative to current communications systems in fighter cockpits. Aerosp Med Hum
      Perform. 2018; 89(10):927-930.

PMID- 30219124
TI  - Letter to the Editor re: The Persistent Issue of Simulator Sickness in Naval
      Aviation Training: Response.

PMID- 30219125
TI  - You're the Flight Surgeon.
AB  - Levy B. You're the flight surgeon: alcohol-induced psychosis. Aerosp Med Hum
      Perform. 2018; 89(10):933-935.

PMID- 30219126
TI  - Boris Yeregov, First Physician in Space, and the Voskhod 1 Spaceflight.

PMID- 30219129
TI  - Pathologic Findings of the Gallbladder in Patients Undergoing Surgery for Biliary
      Dyskinesia.

PMID- 30219127
TI  - This Month in Aerospace Medicine History.

PMID- 30219135
TI  - Primary Epithelioid Hemangioendothelioma of the Heart.

PMID- 30219131
TI  - Parenchyma-Sparing Hepatectomy or Major Hepatectomy for Colorectal Liver
      Metastases?

PMID- 30219136
TI  - Robotic-Assisted Splenectomy for Massive Splenomegaly Secondary to Sarcoidosis.

PMID- 30219137
TI  - Extensive Small Bowel Polyposis of Unknown Origin.

PMID- 30219138
TI  - Venous Embolization of Shotgun Pellets in the Setting of Vascular and Tracheal
      Injury.

PMID- 30219141
TI  - Preface.

PMID- 30219142
TI  - Signaling by Reactive Oxygen Species.

PMID- 30219143
TI  - Reverse total shoulder arhroplasty for the treatment of failed fixation in
      proximal humeral fractures.
AB  - BACKGROUND: This study evaluates the clinical outcomes in patients with proximal
      humerus fractures (PHF) treated with reverse total shoulder arthroplasty (RTSA)
      as a revision procedure for failed fixation that have more than 5 years of follow
      up. MATERIALS AND METHODS: This is a retrospective study of 270 RTSA. The
      inclusion criteria for this study consisted of patients initially treated with
      either open reduction and plate fixation (ORIF) or fixation using an
      intramedullary nail (IMN), who were managed with a single-stage revision to a
      RTSA, and had a minimum of 24 months clinical and radiological follow-up. Six
      patients with failed fixation of displaced PHF were revised with RTSA. One
      patient was excluded from the study because she died. Five shoulders were
      reviewed for the purpose of this study. The patients were evaluated using
      Constant score, relative Constant score and visual analogue scale for pain.
      RESULTS: The mean follow-up was 89 months (65-108). The mean absolute Constant
      score improved from 31, 81 to 44, 2 and the relative Constant score improved from
      31,81% to 67,2%. Mean VAS improved from 6, 8 to 2. One patient rated their
      outcome excellent, 1good, 1 satisfied and 2 poor. CONCLUSION: RTSA is an
      appropriate treatment as a revision surgery for failed fixation of PHF. Patients
      should be adequately warned that they will improve their function but may have
      complications following this salvage procedure.

PMID- 30219144
TI  - Treatment of posttraumatic bone defects of the forearm with vascularized fibular
      grafts. Follow up after fourteen years.
AB  - BACKGROUND: Among several techniques proposed for the reconstruction of
      posttraumatic bone defects of the forearm, that of free vascularised fibular
      graft (FVFG) is one of the most widely used. PATIENTS AND METHOD: We study the
      long-term outcomes of 14 patients who underwent FVFG between 1994 and 2009, with
      a minimum follow up of 8 years and a maximum of 23 years (mean: 13.9 years).
      Demographic, clinical and radiological variables were collected retrospectively.
      The DASH scale was used for clinical assessment. RESULTS: Fourteen patients were
      operated on by the same surgeon, applying FVFG for the reconstruction of
      posttraumatic bone defects of the forearm (three septic non-union of the ulna or
      radius, five radius fractures, two ulna fractures and four fractures of both
      bones). The maximum length of the defect was 11 cm and the minimum length was 6
      cm. In four cases, reconstruction of the two bones was achieved using the double
      barrel technique, and in another four cases, an osteoseptocutaneous flap was
      used. Fixation was performed with 3.5 mm reconstruction plates in thirteen cases
      and with 3.5 mm screws in one case. Consolidation was obtained in 12 cases
      (85.7%) after an average time of 4.2 months (range: 2-6.5 months). In one case,
      consolidation of the proximal ulnar fracture site was not achieved, and in
      another, following the failure of reconstruction attempts, an arthrodesis was
      performed. At the end of the follow-up period, the patients had an average DASH
      score of 17.1 points (range 1.8-68.1). CONCLUSIONS: FVFG is a valid option for
      the reconstruction of posttraumatic bone defects of the forearm. Its use via the
      double barrel method or as an osteocutaneous composite graft enables the
      simultaneous reconstruction of both forearm bones and associated soft tissue
      injuries. Long-term follow-up of patients who have undergone this technique
      confirms its satisfactory functional and radiological results.

PMID- 30219146
TI  - 3D surgical printing for preoperative planning of trabecular augments in
      acetabular fracture sequel.
AB  - We describe the methodical and possibilities of 3D surgical printing in
      preoperative planning for a total hip arthroplasty in acetabular deformity after
      acetabular fractures, showing a case of a 43-year-old with posttraumatic
      arthritis after both column fracture of the left acetabulum that was treated non
      operatively, supporting the do it yourself mode.

PMID- 30219145
TI  - Assessing bone quality through mechanical properties in postmenopausal trabecular
      bone.
AB  - BACKGROUND: The inner structure of trabecular bone is a result of structural
      optimization provided by remodeling processes. Changes in hormonal status related
      to menopause cause bone tissue loss and micro-architectural deterioration with a
      consequent susceptibility to fracture. Accumulation of micro-damage in bone, as a
      function of the rate of production and rate of repair, underlies the development
      of stress fractures, increasing fragility associated to age and osteoporosis,
      especially in transmenopausal women. PATIENTS AND METHODS: Quasi-static and nano
      dynamic mechanical characterization were undertaken in trabecular bone from
      femoral neck biopsies of postmenopausal women. AFM (Atomic Force Microscopy)
      complementary studies were performed to determine nano-roughness (SRa) and the
      fibrils width of collagen. Nanoindentations were used to quantify transmenopausal
      changes in intrinsic mechanical properties of trabecular bone: hardness (Hi),
      modulus of Young (Ei), complex modulus (E*), tan delta (delta), storage modulus
      (E') and loss modulus (E"). RESULTS: As result of the quasi-static measurements,
      0.149 (0.036) GPa and 2.95 (0.73) GPa of Hi and Ei were obtained, respectively.
      As result of the nano-dynamic measurements, 17.94 (3.15), 0.62 (0.10), 13.79
      (3.21 and 6.39 (1.28) GPa of E*, tan (delta), E' and E" were achieved,
      respectively. 101.07 SRa and 831.28 nm of fibrils width were additionally
      obtained. CONCLUSIONS: This study poses a first approach to the measurement of
      bone quality in postmenopausal trabecular bone by combining quasi-static, nano
      DMA analysis and tribology of dentin surface through AFM characterization.

PMID- 30219147
TI  - Salvage for intramedullary nailing breakage after operative treatment of
      trochanteric fractures.
AB  - BACKGROUND: Trochanteric fractures are one of the most common fractures in
      elderly people. The use of intramedullary nails is an option for their treatment,
      especially in unstable patterns. Nail breakage is a rarely reported complication.
      The aim of this study was to determine the prevalence of nail breakage in our
      center. Secondary objectives are to show the management of this complication in
      our institution as well as the technical problems, complications and final
      outcomes of these patients in our hands. MATERIAL AND METHODS: In a retrospective
      case series review between 2010 and 2015, we analyzed 1481 patients with
      trochanteric and subtrochanteric fractures who had been treated by
      cephalomedullary nailing in our centre. 13 patients with nail breakage were
      identified. RESULTS: The percentage failure rate in our institution is 0.87%. 9
      (69.2%) patients were women and 4 (3.8%) were men, with a mean age of 74.6 years
      (range 47-90). In all cases the mechanism of injury was a simple fall from
      standing height. Initial fracture types were: 1 case of AO/OTA 31A1, 6 cases of
      AO/OTA 31A2 and 6 cases of AO/OTA 31A3. Only 3 cases had a good overall reduction
      with a correct TAD, an optimal femoral neck-shaft angle and absence of fracture
      gaps >5 mm after surgery. The average time from the first surgery to the
      diagnosis of implant breakage was 333 days (range 70-1460), 11 months. Breakage
      occurred at the nail junction with the lag screw in 11 cases and in the distal
      nail aperture in 2 cases. CONCLUSIONS: An insufficient reduction with varus and
      fracture gaps >5 mm, the use of short nails in unstable patterns with
      subtrochanteric involvement and patients with certain comorbidities are facts
      observed that can contribute to the development of delayed or nonunion with
      subsequent nail breakage. Different salvage treatments, conversion to hip
      arthroplasty or revision osteosynthesis, may be considered but we think that
      prevention has to be the best treatment.

PMID- 30219148
TI  - Preliminary results using patient-specific 3d printed models to improve
      preoperative planning for correction of post-traumatic tibial deformities with
      circular frames.
AB  - BACKGROUND: Preoperative planning for circular external fixators is considered
      vital towards achieving the best results for complex post-traumatic tibial
      deformities, and patient-specific 3D printed (3DP) models were used here as a
      planning aid. The main goal was to investigate the fidelity of the preoperative
      planning process, by assessing the potential to reduce operative time and
      determining the need to adjust pre-constructed frames intra-operatively. PATIENTS
      AND METHODS: Nine patients (10 limbs) underwent treatment for post-traumatic
      tibial complications using circular external fixation. These were compared to 10
      similar cases where a 3DPM was not used as a pre-operative planning aide (Control
      group). Patient-specific models of affected bones were printed, and preoperative
      planning was performed using conventional techniques and Hexapod-assisted
      software. Detailed planning in a virtual procedure determined osteotomy levels
      and identified sites for wires and half-pins. The prototype of the external
      fixator was locked in this optimized configuration, removed from the model, and
      sterilized prior to the actual procedure. RESULTS: Nine patients with 10 limbs
      were treated for complications following tibial fractures. Seven were infected
      non-unions, and three cases were malunions. For all cases a CT based 3DP model of
      the full tibia was used in the preoperative planning stage. Image analysis
      required a mean of 1.7 h, with an average of 14.9 h to 3D print each model. In
      the control group (without a 3D model), the mean surgical time was 329 min (180
      680). The mean surgical time in the 3DPM group was only 172.4 min (72-240), (p =
      0.024), reducing the surgery time by 48%. For the 3DPM group it was not necessary
      to modify the preassembled frame in any case, while in the Control group, the pre
      constructed frame required intra-operative modifications in 8 of the 10 cases (p
      = 0.0007). CONCLUSION: Using patient-specific 3D models has allowed us to carry
      out meticulous preoperative planning sessions, eliminating the need to modify or
      alter the frame assembly in the operating room, saving substantial surgical time
      and enabling a more precise design of the apparatus. This was especially useful
      in multiplanar deformities and for the spatial configuration of the foot support,
      talus ring, and ankle ring.

PMID- 30219149
TI  - Fractures of the tibial pilon treated by open reduction and internal fixation
      (locking compression plate-less invasive stabilising system): Complications and
      sequelae.
AB  - BACKGROUND: The aim of this study was to evaluate variables that could be related
      to complications and sequelae in fractures of the tibial pilon treated by open
      reduction and internal fixation (ORIF) with a locking compression plate-less
      invasive stabilising system (LCP-LISS). PATIENTS AND METHODS: A total of 137
      fractures treated by ORIF in a 7-year period were analysed. The mean follow-up
      was 3.3 years. We analysed the following variables: age, sex, side, type of
      fracture, energy of the injury, use of provisional external fixation (EF), time
      until ORIF, stages of treatment (one or two), surgical approach, type of bone
      fixation, quality of reduction, use of bone graft, hardware removal, associated
      fractures (fibula and others), functional results (AOFAS scale), early
      complications (infection, skin necrosis) and late complications (nonunion, early
      post-traumatic ankle osteoarthritis [AOA]). RESULTS: According to the AOFAS
      scale, 30.5% of the results were excellent, 46.7% good, 13.1% fair and 9.7% poor.
      The rate of infection was 8.7%, and the rate of skin necrosis requiring flap
      coverage was 15.2%. Furthermore, type 43C3 fractures of the AO classification had
      a higher rate of skin necrosis and flap coverage. The rate of nonunion was 16.3%
      (22 cases, 4 aseptic, 18 infected), and the use of a medial plate was related to
      a higher rate of nonunion than the use of a lateral plate. The rate of early post
      traumatic AOA was 13.1%, and open fractures were related to a higher prevalence
      of nonunion and flap coverage. Both infection and a suboptimal anatomic reduction
      were related to a higher prevalence of fair and poor results. The anteromedial
      approach was associated with a higher prevalence of skin necrosis and early post
      traumatic AOA than the anterolateral approach. CONCLUSION: Optimal reduction and
      stable fixation is paramount to diminishing the rate of complications and
      sequelae after ORIF (LCP-LISS) of these fractures.

PMID- 30219150
TI  - Arthroscopic posterior subtalar arthrodesis for salvage of posttraumatic
      arthritis following calcaneal fractures.
AB  - BACKGROUND: Subtalar arthrodesis is a treatment option for pain due to
      posttraumatic arthritis following calcaneal fractures. The goal of this study is
      to examine the results of arthroscopic subtalar arthrodesis for posttraumatic
      arthritis following calcaneal fractures. PATIENTS AND METHODS: We performed a
      retrospective case series reviewing 37 consecutive patients (36 male) treated for
      posttraumatic arthritis following calcaneal fractures by arthroscopic subtalar
      arthrodesis. The fractures were due to high-energy injuries in 81% of cases, and
      12 fractures (32.4%) had been previously treated with internal fixation. Average
      follow-up was 57.5 months. RESULTS: Average American Orthopedic Foot and Ankle
      Society (AOFAS) scores significantly improved from 49.0 +/- 10.9 points
      preoperatively to 76.0 +/- 8.0 points at final follow-up. Average time to union
      was 12.5 weeks. Six patients (16.2%) suffered complications: superficial wound
      infection (2.7%), symptomatic hardware that warranted removal (5.4%) and nonunion
      (8.1%) presented nonunion. All three cases had prior internal fixation through an
      extensile lateral approach, and fused after a repeat surgery. CONCLUSION:
      Arthroscopic subtalar arthrodesis offers consistent improvement in cases of
      posttraumatic arthritis following calcaneal fractures, with a union rate similar
      to published series of open arthrodesis. We observed more nonunions in patients
      who had been treated previously with internal fixation. In spite of this, we
      continue to recommend arthroscopic subtalar arthrodesis, as it preserves the soft
      tissue envelope better than open techniques.

PMID- 30219151
TI  - Reduced Stroke After Transcatheter Patent Foramen Ovale Closure: A Systematic
      Review and Meta-analysis.
AB  - BACKGROUND: Recent randomized control trials (RCTs) have suggested benefit with
      transcatheter patent foramen ovale (PFO) closure plus antiplatelet therapy over
      medical treatment alone for secondary stroke prevention. MATERIAL AND METHODS:
      Data sources: we searched PubMed and Ovid MEDLINE from the inception until
      November 10, 2017 for RCTs comparing TPFO closure to medical therapy in patients
      with a PFO and a history of cryptogenic stroke. RESULTS: Five RCTs with 3,627
      patients (TPFO closure = 1,829 versus medical therapy =1,798) were included.
      There was a decreased number of post-TPFO closure strokes compared to the medical
      therapy arm; 53 versus 80 strokes (odds ratio [OR] = 0.61, CI: 0.39-0.94, P =
      0.03, I2 = 17%). Transient ischemic attacks occurred in 43 patients after TPFO
      closure versus 60 patients in the medical therapy group (OR = 0.80, CI: 0.53
      1.19, P = 0.26, I2 = 0%). There was a higher incidence of atrial fibrillation in
      the TPFO closure group, which occurred in 75 patients, compared to 12 patients in
      the medical therapy group (OR = 5.23, CI: 2.17-12.59, P = 0.0002, I2 = 43%).
      There was a trend toward a decreased number of neuropsychiatric events in the
      TPFO closure closure group compared to the medical therapy group; 42 versus 67
      neuropsychiatric events (OR = 0.71, CI: 0.48-1.06, P = 0.09, I2 = 0%).
      CONCLUSIONS: TPFO closure plus antiplatelet therapy is superior to medical
      therapy in patients with a PFO and cryptogenic stroke. PFO closure is associated
      with new-onset atrial fibrillation and a trend toward reduced neuropsychiatric
      events.

PMID- 30219153
TI  - Correlations of Circulating Cell-Free DNA With Clinical Manifestations in Acute
      Myocardial Infarction.
AB  - BACKGROUND: The objective of the study was to examine the potential use of
      circulating cell free DNA (cfDNA) in acute myocardial infarction (AMI) patients
      and correlate it with clinical features. Serial monitoring was conducted to
      assess any associations to disease. METHODS: Quantification of cfDNA was
      performed on 130 cardiovascular disease (CVD) patients as well as 30 healthy
      volunteers. Serial samplings were conducted using PicoGreen dsDNA assay. Of the
      130 patients with CVD, 100 had an AMI and measurements were taken during
      treatment. Short and medium intervals serial sampling of patients' blood were
      undertaken. RESULTS: The results were highly correlative of CVD disease status.
      The mean concentration of cfDNA in patients with AMI was 5 folds higher during
      the onset of disease compared with healthy volunteers. The cfDNA content was also
      higher than other patients with CVD. Interestingly, short term monitoring of
      patients with AMI showed distinct trends that highlighted the severity of the
      disease and linked to complication events. Medium term monitoring showed 2
      distinctive groups with 1 that had their cfDNA returned to basal levels and the
      other with persistently elevated cfDNA levels. CONCLUSIONS: Measuring cfDNA in
      patients with CVD offers an alternative approach to monitor the disease and has
      potential clinical applications to identify high-risk individuals.

PMID- 30219152
TI  - Coding and Noncoding Variants in CFH Act Synergistically for Complement
      Activation in Immunoglobulin A Nephropathy.
AB  - BACKGROUND: In immunoglobulin A nephropathy (IgAN), complement activation occurs
      in both the systemic circulation and in situ (glomerular). A recent IgAN-genome
      wide association study (GWAS) identified 1q32 as an IgAN susceptible locus that
      contained the complement regulatory protein coding gene complement factor H
      (CFH). Here, we explored the combined genetic effects of coding and noncoding
      variants in CFH, rs6677604 and rs800292 on complement activation in IgAN.
      METHODS: In total, 1,194 IgAN patients and 900 healthy controls who were the same
      as the Beijing Discovery Cohort in our recent IgAN-GWAS were recruited. The
      genotyping information of rs800292 and rs6677604 were extracted from GWAS data,
      while the information regarding plasma C3 levels and mesangial C3 deposits were
      collected from medical records. RESULTS: We found both rs800292-GG and rs6677604
      GG were risk genotypes for complement activation in IgAN patients, as represented
      by lower plasma C3 levels in IgAN patients with rs800292-GG and a higher
      intensity of glomerular C3 deposits in those with rs6677604-GG, respectively.
      Additionally, IgAN patients with 2 risk genotypes (rs800292-GG and rs6677604-GG)
      showed a higher degree of complement activation compared to those with no risk
      genotypes (rs800292-AA/AG and rs6677604-AA/AG), as represented by both lower
      plasma C3 levels and a higher intensity of glomerular C3 deposits. Moreover, when
      compared to rs800292 or rs6677604 alone, the combined genetic effects of rs800292
      and rs6677604 showed a stronger association with IgAN susceptibility.
      CONCLUSIONS: Our findings suggested that both coding and noncoding variants in
      CFH acted synergistically to regulate the degree of complement activation and
      thereby contributed to IgAN susceptibility.

PMID- 30219154
TI  - BRAF V600E Gene Mutation Is Associated With Bilateral Malignancy of Papillary
      Thyroid Cancer.
AB  - BACKGROUND: Papillary thyroid cancer (PTC) is the most prevalent type of thyroid
      cancer, which is the most common type of endocrine malignancy. Stratification and
      personalized surgical management of PTC patients are the major challenges for
      thyroid surgeons. Though BRAF V600E gene mutation presents in 50-70% of PTCs, it
      is unclear whether BRAF V600E testing could contribute to clinical practice.
      Therefore, this study investigated the association between BRAF V600E mutation
      and clinicopathologic features of PTC to evaluate the benefit of BRAF V600E
      testing to clinical management of PTC. METHODS: In total, 145 patients with PTC
      who underwent bilateral thyroid surgery between July 2016 and December 2016 were
      included in this study. BRAF V600E mutation status and other clinicopathologic
      features were evaluated using the resected samples obtained during the surgery.
      RESULTS: Bilateral PTC was found in 72.8% of the patients with BRAF V600E
      mutation, and in 42.0% of the patients without the mutation. In addition, the
      occurrence of BRAF V600E mutation was higher in cases with bilateral PTC (63.4%)
      than that in cases with unilateral PTC (42.3%). The difference observed above was
      statistically significant (P = 0.014 by chi-square test) and BRAF V600E mutation
      was significantly associated with the bilaterality of PTC (P = 0.0080 by logistic
      regression). CONCLUSIONS: Presence of BRAF V600E mutation has been found to be
      associated with bilaterality of PTC, suggesting that total or near total
      thyroidectomy should be considered for patients with the mutation.

PMID- 30219155
TI  - Modifiable Predictors of In-Hospital Mortality in Patients Undergoing
      Transcatheter Aortic Valve Replacement.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become an
      acceptable therapy for patients with severe aortic valve stenosis at high or
      prohibitive surgical risk. Attempts are ongoing to validate risk prediction
      models for in-hospital mortality after TAVR. Our aim was to define modifiable
      risk factors predictive of in-hospital mortality after TAVR. METHODS: We
      identified patients who underwent TAVR from the 2012 database of the National
      Inpatient Sample. Patients who died during the index hospitalization were
      compared to those that were successfully discharged. The predictors of in
      hospital mortality were analyzed using multivariate logistic regression. RESULTS:
      A total of 1,360 patients (mean age 81 +/- 8.8 years, whites 80.1%, blacks 3.5%)
      had TAVR and 68 (5%) died during hospitalization (chi2 [1, n = 1,360] = 1,101.6,
      P < 0.001). The average length of hospital stay was 8.33 +/- 6.7 days. The
      positive predictors of in-hospital mortality in the unadjusted model were
      comorbidities such as congestive heart failure, coagulopathy, fluid and
      electrolyte disorder, weight loss and history of drug abuse. Hypertension was a
      negative predictor of in-hospital mortality. Following multivariate analysis and
      adjustment for possible confounders, fluid and electrolyte disorder was the only
      significant positive predictor of in-hospital mortality (odds ratio = 1.89, CI:
      1.11-3.22, P = 0.019). The odds of in-hospital mortality were reduced in patients
      with hypertension (odds ratio = 0.45, CI: 0.26-0.78, P = 0.004). CONCLUSIONS:
      Fluid and electrolyte disturbance could be a modifiable predictor of in-hospital
      mortality following TAVR. Efforts should be geared towards reducing its
      occurrence in this patient population.

PMID- 30219156
TI  - Hepatitis B Virus Infection Is Independently Associated With Advanced Colorectal
      Adenoma.
AB  - BACKGROUND: Studies on the association of chronic hepatitis B virus (HBV)
      infection with colonic neoplasm are rare. We aimed to investigate the association
      between chronic HBV infection and the development of colonic adenoma. MATERIALS
      AND METHODS: One hundred thirty-three patients with chronic HBV infection who
      underwent colonoscopic examination, were enrolled. A healthy HBV-uninfected group
      was matched with the HBV group. Those with a previous history of colorectal
      cancer, inflammatory bowel diseases or colorectal surgery were excluded from both
      HBV and HBV-uninfected groups. Clinical information and data on age, sex, body
      mass index, smoking, alcohol consumption and comorbidities were obtained.
      Advanced adenoma was defined as tubular adenoma >=10mm, or adenoma with a villous
      component or high-grade dysplasia. RESULTS: The HBV group had a higher rate of
      colorectal adenoma and advanced adenoma than the HBV-uninfected group. Patients
      in the HBV group had larger colorectal polyps than those in the HBV-uninfected
      group. In the chi square test, HBV DNA positivity was significantly associated
      with colorectal adenoma (P < 0.001) and advanced adenoma (P = 0.007). HBV
      infection (odds ratio [OR] = 23.961, 95% CI: 9.400-61.076), diabetes mellitus (OR
      = 2.633, 95% CI: 1.071-6.473) and age (OR = 1.057, 95% CI: 1.020-1.095) were
      significantly associated with advanced adenoma in the multivariable logistic
      regression analysis. Multivariable logistic regression analysis within the HBV
      group revealed that HBV DNA (OR = 1.236, 95% CI: 1.029-1.485) was associated with
      advanced adenoma. CONCLUSIONS: HBV DNA in patients with HBV infection and HBV
      infection are independently associated with advanced colorectal adenoma
      development.

PMID- 30219157
TI  - Tricuspid Regurgitation Pressure Gradient as a Useful Predictor of Adverse
      Cardiovascular Events and All-Cause Mortality in Patients With Atrial
      Fibrillation.
AB  - BACKGROUND: Tricuspid regurgitation pressure gradient (TRPG) is reportedly a
      predictor of cardiovascular (CV) mortality in patients without atrial
      fibrillation (AF); its relationship with cardiac outcomes in patients with AF has
      never been evaluated. This study aimed to examine the ability of TRPG to predict
      CV events and all-cause mortality in patients with AF. MATERIALS AND METHODS:
      Comprehensive echocardiography was performed in 155 patients with persistent AF.
      Combined CV events were defined as CV mortality, stroke and hospitalization for
      heart failure. RESULTS: During an average follow-up period of 27 months, 57 CV
      events and 31 all-cause deaths occurred. According to multivariate analysis,
      predictors of CV events included diuretic use, decreased left ventricular
      ejection fraction (LVEF), increased ratio of transmitral E velocity (E) to early
      diastolic mitral annular velocity (E') and TRPG. Predictors of all-cause
      mortality included old age, decreased LVEF, increased E/E' and TRPG. Notably, the
      addition of TRPG to a model containing clinical significant parameters, LVEF and
      E/E' significantly improved the values in predicting adverse CV events and all
      cause mortality. CONCLUSIONS: The TRPG is not only a useful predictor of adverse
      CV events and all-cause mortality in patients with AF, it may also provide
      additional prognostic values for CV outcome and all-cause mortality over
      conventional parameters in such patients.

PMID- 30219158
TI  - Gender-Specific Association of Leptin and Adiponectin Genes With Multiple
      Sclerosis.
AB  - BACKGROUND: Adipocytokines such as leptin (LEP) and adiponectin (ADIPOQ)
      represent a link between metabolism, nutritional status and immune responses. The
      present study aimed to determine the possible association between single
      nucleotide polymorphisms of LEP and ADIPOQ genes with multiple sclerosis (MS).
      MATERIALS AND METHODS: Single nucleotide polymorphisms in LEP (rs2167270 or 19G >
      A and rs7799039 or -2,548G > A) and ADIPOQ (rs1501299 or +276G > T and rs266729
      or -11,377C > G) were genotyped in 305 patients and 255 healthy individuals using
      polymerase chain reaction-restriction fragment length polymorphism. Sera levels
      of leptin and adiponectin were measured using enzyme-linked immunosorbent assay.
      RESULTS: The frequencies of low leptin producer rs2167270GG genotype and
      rs2167270G allele were significantly lower in patients with MS compared to those
      of controls (for GG genotype: 39.7% and 49.8%, respectively; P = 0.01; for G
      allele: 63.3% and 68.8%, respectively; P = 0.05). Both polymorphisms in ADIPOQ
      did not show any significant association with disease susceptibility, though
      after gender categorization the frequency of high adiponectin producer
      rs1501299TT genotype and rs1501299T allele were significantly higher in male
      controls compared to male patients (TT genotype: P = 0.006; T allele: P = 0.006).
      Additionally, rs1501299TT genotype in ADIPOQ was associated with susceptibility
      to primary progressive multiple sclerosis (PP-MS) (P = 0.02). Moreover, while the
      sera levels of leptin were only different between male patients and controls (P =
      0.05), adiponectin levels were significantly higher in total and female healthy
      controls (P < 0.001, P = 0.002, respectively). CONCLUSIONS: Our findings provide
      evidence to support the hypothesis that functional ADIPOQ and LEP gene
      polymorphisms are associated with susceptibility to MS and its clinical forms.

PMID- 30219159
TI  - Silent Information Regulator 1 Negatively Regulates Atherosclerotic Angiogenesis
      via Mammalian Target of Rapamycin Complex 1 Signaling Pathway.
AB  - BACKGROUND: This study aimed to investigate the interactions between silent
      information regulator 1 (SIRT1) and mammalian target of rapamycin (mTOR) in
      intraplaque angiogenesis and their potential mechanisms through in vivo and in
      vitro studies. METHODS: An atherosclerosis model was established in 12 rabbits on
      a high-cholesterol diet. The rabbits were equally divided into 3 groups: a
      control group (high-lipid diet), RAP group (high-lipid diet supplemented with
      rapamycin) and RAP + NAM group (high-lipid diet supplemented with rapamycin and
      nicotinamide). At the end of 4 weeks, the area of plaques in the aorta was
      determined and the protein expression of CD31 and vascular endothelial growth
      factor (VEGF) was detected through hematoxylin and eosin staining and
      immunohistochemical staining, respectively. For in vitro study, a hypoxia model
      was established in human umbilical vein endothelial cells (HUVECs) by using the
      chemical method (CoCl2). The MTT assay, scratch assay and tube formation assay
      were performed to evaluate the proliferation and angiogenesis abilities of
      HUVECs. Reverse transcription polymerase chain reaction was used to examine the
      mRNA levels of SIRT1, hypoxia-inducible factor-1alpha (HIF-1alpha), mTOR and p70
      ribosomal S6 kinase (p70S6K). Western blotting was used to examine the protein
      levels of SIRT1, HIF-1alpha, mTOR, p-mTOR, p-raptor and p-p70S6K. RESULTS: The
      results of the in vivo study indicated a significant inhibitory effect of
      rapamycin on plaque size and intraplaque angiogenesis (0.05 +/- 0.02mm2 versus
      5.44 +/- 0.50mm2, P < 0.05). This effect was attenuated by nicotinamide (0.76 +/-
      0.15mm2 versus 0.05 +/- 0.02mm2, P < 0.05). Compared with the RAP group, CD31-
      and VEGF-positive vessels were abundant in the RAP + NAM group. The RAP group
      showed lower expression of p-mTOR, p-p70S6K and HIF-1alpha than did the control
      group (P < 0.05), whereas the RAP + NAM group showed slightly higher expression
      of these factors than did the RAP group (P < 0.05). Furthermore, in vitro studies
      revealed that the inhibitory effect of rapamycin on the angiogenic ability of
      HUVECs and its significant inhibitory effects on the protein level of HIF-1alpha
      and the phosphorylation of proteins involved in the mTORC1 pathway, including
      mTOR, raptor and p70S6K (P < 0.05), were enhanced by cotreatment with SRT1720 and
      rapamycin (P < 0.05). In contrast to mTOR and SIRT1, the mRNA levels of p70S6K
      and HIF-1alpha were reduced by rapamycin (P < 0.05) and further reduced by
      cotreatment with SRT1720 and rapamycin. CONCLUSIONS: The study results indicate
      that SIRT1 might negatively regulate atherosclerotic angiogenesis via mTORC1 and
      HIF-1alpha signaling pathway and cointervention of SIRT1 and mTOR may serve as a
      crucial therapeutic strategy in cardiovascular medicine.

PMID- 30219160
TI  - Evaluation and Management of Gross Hematuria in Autosomal Dominant Polycystic
      Kidney Disease: A Point of Care Guide for Practicing Internists.
AB  - Gross hematuria is common in autosomal dominant polycystic kidney disease
      (ADPKD). It is an alarming symptom and may be the first manifestation of ADPKD.
      Cyst hemorrhage is a frequent cause of hematuria in ADPKD while other
      differential diagnoses include cyst infection, urinary tract infection, renal
      stones and an underlying malignancy. Knowledge of the precipitating factors and
      clinical presentation of these conditions will help practicing internists in
      performing an appropriate evaluation and management of these entities and their
      complications, as well as executing timely referrals to subspecialists when
      indicated.

PMID- 30219161
TI  - Recurrent Severe Hypoinsulinemic Hypoglycemia Responsive to Temozolomide and
      Bevacizumab in a Patient With Doege-Potter Syndrome.
AB  - Nonislet cell tumor hypoglycemia is rare. We highlight the diagnosis and
      treatment of recurrent severe hypoglycemia in a 49-year-old woman with malignant
      solitary fibrous tumor of the pleura (Doege-Potter syndrome). The clinical,
      laboratory and radiologic findings of the case are presented and a brief
      literature review is provided. Of note, imaging studies showed a large mass in
      the right hemithorax and pathology and immunehistochemical stains confirmed a
      malignant solitary fibrous tumor of the pleura. She was a poor surgical candidate
      owing to a large tumor burden. She was treated with a combination of temozolomide
      and bevacizumab to which she responded with resolution of hypoglycemia. The
      treatment of choice for hypoglycemia in patients with the Doege-Potter syndrome
      is surgical excision. We here report that a combination of temozolomide and
      bevacizumab may be a viable option in patients with inoperable disease.

PMID- 30219162
TI  - The Summer Enrichment Program: A Multidimensional Experiential Enriching
      Experience for Junior Medical Students.

PMID- 30219163
TI  - Experiential Learning in Medical Education.

PMID- 30219164
TI  - Experiential Learning in Undergraduate Education - Doing and Reflecting.

PMID- 30219165
TI  - Does Timing Matter? Using Lactate to Predict Outcomes in Sepsis.

PMID- 30219166
TI  - An Offer We Cannot Refuse: Cell-Free DNA as a Novel Biomarker of Myocardial
      Infarction.

PMID- 30219167
TI  - The Dust Bowl in the US: An Analysis Based on Current Environmental and Clinical
      Studies.
AB  - The Dust Bowl occurred in the Central Plains states in the United States between
      1930 and 1940. Prolonged drought, intense recurrent dust storms and economic
      depression had profound effects on human welfare. The causes included increased
      farming on marginal land, poor land management, and prolonged drought. There was
      a significant increase in the number of cases of measles, increased
      hospitalization for respiratory disorders and increased infant and overall
      mortality in Kansas during the Dust Bowl. Recent scientific studies have
      demonstrated that dust transmits measles virus, influenza virus and Coccidioides
      immitis, and that mortality in the United States increases following dust storms
      with 2-3-day lag periods. Advances in technology have provided information about
      the composition of dust and the transfer of microbial pathogens in dust and
      provided the framework for reducing the economic and health consequences of the
      next prolonged drought in the United States.

PMID- 30219168
TI  - Timing of Repeated Lactate Measurement in Patients With Septic Shock at the
      Emergency Department.
AB  - BACKGROUND: The objective of this study was to evaluate the prognostic value of
      lactate levels during the first 12 hours after shock development and to identify
      the optimal timing for repeated lactate measurements in patients with septic
      shock. METHODS: We conducted a retrospective cohort study using a prospective
      data registry, and enrolled 2,226 consecutive adult patients with septic shock
      between January 2010 and December 2015. Blood lactate was measured at shock
      development, and after 2, 4, 6 and 12 hours (T0, T2, T4, T6 and T12) during
      protocol-driven resuscitation bundle therapy. The prognostic value of lactate
      levels for 28-day mortality was analyzed using logistic regression and receiver
      operating characteristic curve analysis. RESULTS: A total of 829 patients with
      septic shock were included in the study, among whom 211 died during the study
      period. The lactate levels at each time point were associated with increased 28
      day mortality, and the lactate level at 6 hours had the greatest prognostic value
      (area under the curve of T0 = 0.61; T2 = 0.65; T4 = 0.69; T6 = 0.72 and T12 =
      0.62, and odds ratio (OR) of T0, 1.17 [95% CI: 1.11-1.23]; T2, 1.23 [95% CI: 1.17
      1.30]; T4, 1.30 [95% CI: 1.22-1.38]; T6, 1.33 [95% CI: 1.26-1.42] and T12, 1.24
      [95% CI: 1.19-1.30]). Hyperlactatemia over 2mmol/L and 4mmol/L at 6 hours from
      shock was associated with 4-times higher mortality (>=2mmol/L, OR = 3.89 [95% CI:
      2.48-6.09]; >=4mmol/L, OR = 3.93 [95% CI: 2.83-5.44]). CONCLUSIONS: During the
      first 12 hours following shock development, the optimal time point of repeated
      blood lactate measurement was 6 hours, which was the greatest prognostic value
      for mortality.

PMID- 30219169
TI  - Kallmann Syndrome With Micropenis.

PMID- 30219170
TI  - Central Retinal Artery Occlusion Following Hyaluronic Acid Fillers Injection.

PMID- 30219171
TI  - Allergen immunotherapy.

PMID- 30219172
TI  - Life in the FAST lane.

PMID- 30219173
TI  - New diagnostic criteria for eosinophilic esophagitis: Will they influence our
      practice?

PMID- 30219175
TI  - Erratum.

PMID- 30219174
TI  - Hidden allergens in food allergy.

PMID- 30219176
TI  - Diane E. Schuller, MD (1943-2018).

PMID- 30219177
TI  - Editorial: Drug Nanoparticles and Nano-Cocrystals: From Production and
      Characterization to Clinical Translation.

PMID- 30219178
TI  - Corrigendum to "Tropidoatractidae fam. nov., a deep branching lineage of Metopida
      (Armophorea, Ciliophora) found in diverse habitats and possessing prokaryotic
      symbionts" [Protist 169 (July (3)) (2018) 362-405].

PMID- 30219180
TI  - Guest editorial: Innate lymphocytes: Development, homeostasis, and disease.

PMID- 30219179
TI  - A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than
      1,000 BRCA1 Missense Substitution Variants on Protein Function.
AB  - Loss-of-function pathogenic variants in BRCA1 confer a predisposition to breast
      and ovarian cancer. Genetic testing for sequence changes in BRCA1 frequently
      reveals a missense variant for which the impact on cancer risk and on the
      molecular function of BRCA1 is unknown. Functional BRCA1 is required for the
      homology-directed repair (HDR) of double-strand DNA breaks, a critical activity
      for maintaining genome integrity and tumor suppression. Here, we describe a
      multiplex HDR reporter assay for concurrently measuring the effects of hundreds
      of variants of BRCA1 for their role in DNA repair. Using this assay, we
      characterized the effects of 1,056 amino acid substitutions in the first 192
      residues of BRCA1. Benchmarking these results against variants with known effects
      on DNA repair function or on cancer predisposition, we demonstrate accurate
      discrimination of loss-of-function versus benign missense variants. We anticipate
      that this assay can be used to functionally characterize BRCA1 missense variants
      at scale, even before the variants are observed in results from genetic testing.

PMID- 30219181
TI  - Editor's Page.

PMID- 30219182
TI  - PET/Computed Tomography and PET/MR Imaging: Basic Principles, Methodology, and
      Imaging Protocol for Musculoskeletal Applications.
AB  - In this review, the fundamentals of PET/CT and PET/MRI are discussed, with their
      implications for evaluation of musculoskeletal disorders. This article also
      provides an overview of FDG and non-FDG PET tracers, the different PET, CT and
      MRI protocols and how they can be employed in an individualized manner in various
      diseased conditions. The present role and the shortcomings of both modalities
      have been enumerated.

PMID- 30219183
TI  - 18F-Sodium Fluoride PET/CT and PET/MR Imaging of Bone and Joint Disorders.
AB  - 18F-sodium fluoride (18F-NaF) PET/CT provides high sensitivity and specificity
      for the assessment of bone and joint diseases. It is able to accurately
      differentiate malignant from benign bone lesions, especially when using dynamic
      quantitative approaches. Its high-quality, clinical accuracy, and high
      feasibility for patient management and greater availability of PET/CT scanners as
      well as decreasing trend of the cost of radiotracer all indicate the need to
      consider the use of 18F-NaF PET/CT as standard bone imaging, particularly in
      malignant diseases of the skeleton.

PMID- 30219184
TI  - Radionuclide Therapy for Bone Metastases: Utility of Scintigraphy and PET Imaging
      for Treatment Planning.
AB  - The skeleton is a common site for cancer metastases. Bone metastases are a major
      cause of morbidity and mortality and associated with pain, pathologic fractures,
      spinal cord compression, and decreased survival. Various radionuclides have been
      used for pain therapy. Recently, an alpha-emitter has been shown to improve
      overall survival of patients with bone metastases from castration-resistant
      prostate cancer and was approved as a therapeutic agent. The aim of this article
      is to provide an overview regarding state of the art radionuclide therapy options
      for bone metastases, with focus on the role of PET imaging in therapy planning.

PMID- 30219185
TI  - Whole-Body MR Imaging: The Novel, "Intrinsically Hybrid," Approach to Metastases,
      Myeloma, Lymphoma, in Bones and Beyond.
AB  - Whole-body MR imaging (WB-MR imaging) has become a modality of choice for
      detecting bone metastases in multiple cancers, and bone marrow involvement by
      multiple myeloma or lymphoma. Combination of anatomic and functional sequences
      imparts an inherently hybrid dimension to this nonirradiating tool and extends
      the screening of malignancies outside the skeleton. WB-MR imaging outperforms
      bone scintigraphy and CT and offers an alternative to PET in many tumors by time
      of lesion detection and assessment of treatment response. Much work has been done
      to standardize procedures, optimize sequences, validate indications, confirm
      preliminary research into new applications, rendering clinical application more
      user-friendly.

PMID- 30219186
TI  - MR Imaging of Joint Infection and Inflammation with Emphasis on Dynamic Contrast
      Enhanced MR Imaging.
AB  - Contrast-enhanced MR imaging (CE-MR imaging) is recommended for diagnosis and
      monitoring of infectious and most inflammatory joint diseases. CE-MR imaging
      clearly differentiates soft and bony tissue from fluid collections and infectious
      debris. To improve imaging information, a dynamic CE-MR imaging sequence (DCE-MR
      imaging) sequence can be applied using fast T1-weighted sequential image
      acquisition during contrast injection. Use of DCE-MR imaging allows robust
      extraction of quantitative information regarding blood flow and capillary
      permeability, especially when dedicated analysis methods and software are used to
      analyze contrast kinetics. This article describes principles of DCE-MR imaging
      for the assessment of infectious and inflammatory joint diseases.

PMID- 30219187
TI  - MR Imaging of the Musculoskeletal System Using Ultrahigh Field (7T) MR Imaging.
AB  - MR imaging is an indispensable instrument for the diagnosis of musculoskeletal
      diseases. In vivo MR imaging at 7T offers many advantages, including increased
      signal-to-noise ratio, higher spatial resolution, improved spectral resolution
      for spectroscopy, improved sensitivity for X-nucleus imaging, and decreased image
      acquisition times. There are also however technical challenges of imaging at a
      higher field strength compared with 1.5 and 3T MR imaging systems. We discuss the
      many potential opportunities as well as the challenges presented by 7T MR imaging
      systems and highlight recent developments in in vivo research imaging of
      musculoskeletal applications in general and cartilage, skeletal muscle, and bone
      in particular.

PMID- 30219188
TI  - The Role of Dual-Energy Computed Tomography in Musculoskeletal Imaging.
AB  - Dual-energy computed tomography (DECT) enables material decomposition and virtual
      monochromatic images by acquiring 2 different energy X-ray data sets. DECT can
      detect musculoskeletal pathologic conditions that CT alone cannot, and that would
      otherwise require MR imaging. In this review, the authors discuss several useful
      techniques and applications of DECT in musculoskeletal research: virtual
      monochromatic images, virtual noncalcium images, gout, iodine map, and tendons.

PMID- 30219189
TI  - Percutaneous Minimally Invasive Thermal Ablation of Musculoskeletal Lesions:
      Usefulness of PET-Computed Tomography.
AB  - This article discusses the role of PET-computed tomography in percutaneous
      minimally invasive ablation of osseous metastases including diagnosis and
      preprocedural factors related to patient selection and procedure planning,
      intraprocedural imaging guidance, and posttreatment imaging assessment.

PMID- 30219190
TI  - Musculoskeletal Pitfalls on Fluorodeoxyglucose F 18 PET-Computed Tomography:
      Pictorial Review.
AB  - A wide range of musculoskeletal processes can demonstrate increased uptake on PET
      computed tomography (CT) with fluorodeoxyglucose (FDG) F 18, including reactive,
      benign neoplastic, inflammatory, traumatic, posttreatment, and arthritic
      conditions that may mimic malignancy. In addition, physiologic causes of
      increased FDG uptake such as asymmetric muscle use and presence of brown fat can
      lead to increased FDG uptake and potential false-positive results. This article
      presents various case examples of non-malignant musculoskeletal hypermetabolism
      on 18F-FDG PET-CT and describes useful tools to avoid the potential pitfall of
      misinterpreting these as malignancy.

PMID- 30219191
TI  - PET in the Diagnostic Management of Soft Tissue Sarcomas of Musculoskeletal
      Origin.
AB  - Soft tissue sarcomas (STSs) account for less than 1% of adult solid tumors and
      about 7% of pediatric malignancies, causing 2% of cancer-related deaths. With the
      advent of PET-computed tomography (CT), the value of (18) fluorine-2-fluoro-2
      deoxy-d-glucose (FDG) PET imaging to improve the management of STSs has been
      explored. FDG PET imaging has been found useful in restaging and treatment
      response assessment. This article reviews current knowledge and application of
      FDG PET-CT in initial diagnosis, staging, restaging, treatment response
      monitoring, and prognosis, with a brief overview of the most common histologic
      subtypes of STS.

PMID- 30219192
TI  - Applications of PET/CT and PET/MR Imaging in Primary Bone Malignancies.
AB  - Primary bone malignancies are characterized with anatomic imaging. However, in
      recent years, there has been an increased interest in PET/computed tomography
      scanning and PET/MRI with fludeoxyglucose F 18 for evaluating and staging
      musculoskeletal neoplasms. These hybrid imaging modalities have shown promise
      largely owing to their high sensitivity, ability to perform more thorough
      staging, and ability to monitor treatment response. This article reviews the
      current role of PET/computed tomography scanning and PET/MRI in primary
      malignancies of bone, with an emphasis on imaging characteristics, clinical
      usefulness, and current limitations.

PMID- 30219193
TI  - Evolving Role of PET-Computed Tomography and PET-MR Imaging in Assessment of
      Musculoskeletal Disorders and Its Potential Revolutionary Impact on Day-to-Day
      Practice of Related Disciplines.

PMID- 30219194
TI  - Cardioprotective Therapies for Myocardial Edema for Patients With Takotsubo
      Syndrome?

PMID- 30219195
TI  - [Combined spinal-epidural block for labor analgesia. Comparative study with
      continuous epidural block].
AB  - INTRODUCTION: Lumbar epidural block is an effective and routinely used technique
      for labor pain relief, and the combined spinal-epidural block has the benefit of
      using lower doses of local anesthetics and rapid onset of analgesia. The
      objective of this study was to evaluate the effectiveness and safety of two
      anesthetic techniques: combined spinal-epidural block and continuous epidural
      block in pregnant women for labor analgesia. METHODS: Eighty patients, ASA II and
      III, with cephalic presentation and cervical dilation between 5 and 6
      centimeters, undergoing labor analgesia, allocated in two groups according to the
      anesthetic technique: combined spinal-epidural (GI) and continuous epidural
      (GII). Pain severity before the blockade, time to complete analgesia, degree of
      motor blockade, time to full cervical dilation, duration of the second stage of
      labor, pain severity during the 1st and 2nd stage of labor, type of delivery, use
      of oxytocin during labor, maternal cardiocirculatory and respiratory parameters
      and adverse events, and neonatal repercussions were recorded. RESULTS: At the
      time of anesthesia, pain severity was similar in both groups. Pain relief was
      faster in GI (4.5+/-1.5min) when compared to GII (11.6+/-4.6min) p=0.01; pain
      scores in the first and second stages of delivery were lower in GI (0.9+/-0.3 and
      1.8+/-0.7, respectively) when compared to GII (1.9+/-0.6 and 2.2+/-0.5,
      respectively), with p=0.01 only in the first stage of labor; there was need for
      local anesthetics supplementation in GII; there were more frequent spontaneous
      deliveries in GI (80% of patients) than in GII (50%) (p=0.045) and more frequent
      use of instrumental (p=0.03) in GII (12 patients) compared to GI (4 patients);
      the frequency of cesarean deliveries was significantly higher (p=0.02) in Group
      II than in Group I, with 4 cases in GI and 8 cases in GII; absence of maternal
      cardiocirculatory and respiratory changes and neonatal repercussions; more
      frequent pruritus in GI (10 patients) and (0 patients in GII) (p=0.02).
      CONCLUSION: The combined blockade proved to be effective with better quality of
      analgesia and greater comfort for pregnant women, constituting a good option for
      the practice of obstetric analgesia.

PMID- 30219196
TI  - Catheter ablation of rotational activity in atrial fibrillation: A barren oasis?

PMID- 30219197
TI  - The authors reply: Treatment of patients with restenosis of drug-eluting stents.

PMID- 30219198
TI  - Low-molecular-weight heparin for the prevention and treatment of placenta
      mediated pregnancy complications: The tides have shifted.

PMID- 30219199
TI  - Erratum.

PMID- 30219201
TI  - Recombinant Membrane Protein Methods.

PMID- 30219200
TI  - Industrial production of sourdoughs for the baking branch - An overview.
AB  - Sourdoughs are produced both in artisanal and industrial size. Sourdough
      manufacturers deliver the baking branch either with starters for production of in
      house sourdoughs or with fully fermented sourdough products. In the latter case
      sourdough production is separated in time and space from the bread production. A
      big part of this convenience products are dried sourdoughs, which are mainly
      produced from rye and wheat flour, but also from other starch containing plants,
      like pseudocereals or legumes. The requirements regarding the raw materials used
      differ from that used for baking bread. The most applied drying techniques for
      sourdoughs are drum and spray-drying. Compared with other foods, sourdough and
      sourdough products have only a low risk regarding food safety due to pH < 4.2,
      however formation of biogenic amines or acrylamide has taken into account. More
      tools for sourdough authentication are needed but, before developing and
      validating methods, it would be necessary to include different sourdough products
      in a clear regulatory framework.

PMID- 30219202
TI  - Registry of left atrial appendage closure and initial experience with
      intracardiac echocardiography.
AB  - INTRODUCTION: Percutaneous closure of the left atrial appendage (LAA) is a
      promising therapy in patients with atrial fibrillation with high risk for stroke
      and contraindication for oral anticoagulation (OAC). Intracardiac
      echocardiography (ICE) may make this percutaneous procedure feasible in patients
      in whom transesophageal echocardiography (TEE) is inadvisable. Our aim was to
      assess the efficacy and safety of LAA closure and the feasibility of ICE compared
      to TEE to guide the procedure. METHODS: In this cohort study of patients who
      underwent LAA closure between May 2010 and January 2017, clinical and imaging
      assessment was performed before and after the procedure. RESULTS: In 82 patients
      (mean age 74+/-8 years, 64.4% male) the contraindications for OAC were severe
      bleeding or anemia (65%), high bleeding risk (14%), labile INR (16%), or
      recurrent embolic events (5%). The procedural success rate was 96.3%. The
      procedure was guided by TEE or ICE, and no statistically significant differences
      were observed between the two techniques. During follow-up, one patient had an
      ischemic stroke at 12 months, two had bleeding complications at six months, and
      there were four non-cardiovascular deaths. Embolic and bleeding events were less
      frequent than expected from the observed CHA2DS2VASc (0.6% vs. 6.3%; p<0.001) and
      HAS-BLED (1.2% vs. 4.1%; p<0.001) risk scores. CONCLUSIONS: In this population
      percutaneous LAA closure was shown to be safe and effective given the lower
      frequency of events than estimated by the CHA2DS2VASc and HAS-BLED scores. The
      clinical and imaging results of procedures guided by ICE in the left atrium were
      not inferior to those guided by TEE.

PMID- 30219204
TI  - The never-ending story of the ideal valve.

PMID- 30219203
TI  - Effective B cell activation in vitro during viremic HIV-1 infection with
      surrogate T cell stimulation.
AB  - Identifying HIV-1-associated B cell defects and responses to activation may
      direct interventions to circumvent their impaired antibody responses to infection
      and vaccines. Among 34 viremic HIV-1-infected and 20 seronegative control adults,
      we measured baseline frequencies and activation of B and T cell subsets,
      expression of activation-induced cytidine deaminase (AID), potential determinants
      of B cell activation in vivo and B and T cell responses in vitro. At baseline,
      HIV-1 infection was associated with increased IgM memory and decreased anergic
      cell frequencies, as well as increased activation in all 10 B cell subsets
      compared with controls. HIV-1 status, TFH activation, and BAFF were significant
      potential drivers of B cell activation. Despite high baseline activation among
      HIV-1-infected subjects, stimulation in vitro with combined surrogates for
      antigen (anti-IgM), cognate (CD40 ligand) and soluble T cell factors (IL-4)
      elicited comparable B cell activation, transitions from naive to class-switched
      memory cells and AID expression in both groups. In summary, viremic HIV-1
      infection perturbs circulating B cell subsets and activation at each stage of B
      cell maturation. However, that appropriate stimulation of B cells elicits
      effective activation and maturation provides impetus for advancing vaccine
      development to prevent secondary infections by circumventing early B cell
      defects.

PMID- 30219206
TI  - [Is reduction of hyperglycemia associated with a cardiovascular benefit?]
AB  - We have a large body of evidence showing that hyperglycemia is a cardiovascular
      risk factor and that its reduction decreases the risk for cardiovascular events.
      Indeed, epidemiological studies have clearly shown that hyperglycemia is a strong
      and independent factor for cardiovascular disease. In addition, we have many
      pathophysiological studies demonstrating the direct role of hyperglycemia in the
      development of atherosclerosis. Hyperglycemia, by stimulating protein kinase C,
      increases the production of pro-inflammatory cytokines, of adhesion molecules and
      of endothelin-1 and, by stimulating the polyol pathway, promotes the oxidative
      stress. Furthermore, chronic hyperglycemia leads to the accumulation of advanced
      glycation end-products that modify the structure of the arterial wall and, as a
      consequence, will increase the risk for the development of atherosclerosis.
      Moreover, prolonged intervention studies have shown that reduction of
      hyperglycemia is associated with a significant decrease in the risk for major
      cardiovascular events. Thus, hyperglycemia is a cardiovascular risk factor which
      is characterized by the fact that it induces profound modifications of the
      arterial wall and that it is necessary to correct hyperglycemia during enough
      time to obtain a cardiovascular benefit.

PMID- 30219205
TI  - [Quadrivalent influenza vaccine: What is changed and what are the benefits?]
AB  - Currently, circulating viruses responsible for annual seasonal influenza
      epidemics belong to two influenza A subtypes, A(H1N1) and A(H3N2), and to two
      antigenically distinct type B lineages, B/Yamagata and B/Victoria lineages. Like
      diseases due to influenza A virus, influenza B virus diseases may have severe
      consequences and should be prevented. Until now, in France, the vaccines used to
      prevent seasonal influenza were trivalent, systematically targeting viruses
      belonging to both A subtypes and to one or other of the B lineages. The
      protective efficacy of trivalent vaccines is diminished during the seasons when
      viruses belonging to both B lineages cocirculated or when the circulating
      dominant type B virus belonged to a lineage different from that targeted by the
      vaccine strain. By targeting viruses belonging to both B lineages, quadrivalent
      vaccines improve the antigenic concordance between circulating and vaccine type B
      strains. Three inactivated quadrivalent vaccines are authorized for marketing in
      France and should be available for the 2018-2019 season. It is expected that, by
      providing enlarged protection, these quadrivalent influenza vaccines will improve
      vaccine efficacy, the confidence in immunization of the public, the satisfaction
      of health professionals, and ultimately will help to complete immunization
      coverage.

PMID- 30219207
TI  - Disparities between English and Spanish in readability of online endodontic
      information for laypeople.
AB  - BACKGROUND: In this study, the authors assessed the readability of online
      endodontic information in English and Spanish. METHODS: The authors performed a
      systematic search in Google in May 2016. Search queries were "root canal
      treatment" and "?Que es una endodoncia?" without limits or filters. The authors
      assessed English readability by using Flesch-Kincaid Reading Grade Level, Flesch
      Reading Ease Score, Gunning Fog Index, Coleman-Liau index, automated readability
      index, and Simple Measure of Gobbledygook (SMOG) index. The authors calculated
      readability for Spanish by using the Fernandez-Huerta index and INFLESZ (Ines
      Barrio). RESULTS: The authors assessed the first 100 consecutive sites identified
      with each search strategy and selected 117 sites. Readability scores for English
      language sites were in the category of normal to read, easily understood by 13-
      through 15-year-old students (Flesch Reading Ease Score, 63, interquartile range
      (IQR) [53.9-66.2]; Gunning Fog Index, 10.4, IQR [8.8-12]; Coleman-Liau index,
      12.5, IQR [11.6-13.3]; and automated readability index, 8.6, IQR [6.7-9.8]). SMOG
      results led to the estimation that only 7 years of education would be needed to
      understand these contents (SMOG, 7.6, IQR [6.5-8.8]). Spanish-language sites had
      a readability index normal for an adult, equivalent to a seventh or eighth school
      year (Fernandez-Huerta, 62.3, IQR [59.7-66.6]; INFLESZ, 57.5, IQR [55.1-62.1]).
      The authors found that 36.6% of English-language sites had some degree of
      difficulty for readers to understand their contents, whereas 23% of Spanish
      language sites had some degree of difficulty (14.46; 95% confidence interval, 
      3.16 to 30.08). CONCLUSIONS: Spanish- and English-language electronic health
      information about endodontic treatment is acceptable to read, but-particularly
      for English-language sites-there is an important proportion of sites scoring
      difficulty levels well above the recommendations. PRACTICAL IMPLICATIONS: The
      internet is a useful tool for communicating with patients, but available
      endodontic information is difficult for laypeople to understand. Endodontists
      should produce relevant materials in plain language to overcome this problem.

PMID- 30219208
TI  - Increased Number and Activity of a Lateral Subpopulation of Hypothalamic
      Orexin/Hypocretin Neurons Underlies the Expression of an Addicted State in Rats.
AB  - BACKGROUND: The orexin (hypocretin) system is important for reward-driven
      motivation but has not been implicated in the expression of a multiphenotype
      addicted state. METHODS: Rats were assessed for economic demand for cocaine
      before and after 14 days of short access, long access, or intermittent access
      (IntA) to cocaine. Rats were also assessed for a number of other DSM-5-relevant
      addiction criteria following differential access conditions. Orexin system
      function was assessed by quantification of numbers and activity of orexin cells,
      pharmacological blockade of the orexin-1 receptor, and subregion-specific
      knockdown of orexin cell populations. RESULTS: IntA produced a cluster of
      addiction-like behaviors that closely recapitulate key diagnostic criteria for
      addiction to a greater extent than long access or short access. IntA was
      accompanied by an increase in number and activity of orexin-expressing neurons
      within the lateral hypothalamic subregion. This increase in orexin cell number
      and activity persisted during protracted withdrawal from cocaine for at least 150
      days and was accompanied by enhanced incubation of craving in the same rats.
      Selective knockdown of lateral hypothalamic orexin neurons reduced motivation for
      cocaine, and orexin-1 receptor signaling played a larger role in drug seeking
      after IntA. CONCLUSIONS: We provide the first evidence that lateral hypothalamic
      orexin system function extends beyond general reward seeking to play a critical
      role in expression of a multiphenotype addiction-like state. Thus, the orexin
      system is a potential novel target for pharmacotherapies designed to treat
      cocaine addiction. In addition, these data point to the IntA model as a preferred
      approach to modeling addiction-like behavior in rats.

PMID- 30219209
TI  - Adolescent Delta9-Tetrahydrocannabinol Exposure and Astrocyte-Specific Genetic
      Vulnerability Converge on Nuclear Factor-kappaB-Cyclooxygenase-2 Signaling to
      Impair Memory in Adulthood.
AB  - BACKGROUND: Although several studies have linked adolescent cannabis use to long
      term cognitive dysfunction, there are negative reports as well. The fact that not
      all users develop cognitive impairment suggests a genetic vulnerability to
      adverse effects of cannabis, which are attributed to action of Delta9
      tetrahydrocannabinol (Delta9-THC), a cannabis constituent and partial agonist of
      brain cannabinoid receptor 1. As both neurons and glial cells express cannabinoid
      receptor 1, genetic vulnerability could influence Delta9-THC-induced signaling in
      a cell type-specific manner. METHODS: Here we use an animal model of inducible
      expression of dominant-negative disrupted in schizophrenia 1 (DN-DISC1)
      selectively in astrocytes to evaluate the molecular mechanisms, whereby an
      astrocyte genetic vulnerability could interact with adolescent Delta9-THC
      exposure to impair recognition memory in adulthood. RESULTS: Selective expression
      of DN-DISC1 in astrocytes and adolescent treatment with Delta9-THC
      synergistically affected recognition memory in adult mice. Similar deficits in
      recognition memory were observed following knockdown of endogenous Disc1 in
      hippocampal astrocytes in mice treated with Delta9-THC during adolescence. At the
      molecular level, DN-DISC1 and Delta9-THC synergistically activated the nuclear
      factor-kappaB-cyclooxygenase-2 pathway in astrocytes and decreased
      immunoreactivity of parvalbumin-positive presynaptic inhibitory boutons around
      pyramidal neurons of the hippocampal CA3 area. The cognitive abnormalities were
      prevented in DN-DISC1 mice exposed to Delta9-THC by simultaneous adolescent
      treatment with the cyclooxygenase-2 inhibitor, NS398. CONCLUSIONS: Our data
      demonstrate that individual vulnerability to cannabis can be exclusively mediated
      by astrocytes. Results of this work suggest that genetic predisposition within
      astrocytes can exaggerate Delta9-THC-produced cognitive impairments via
      convergent inflammatory signaling, suggesting possible targets for preventing
      adverse effects of cannabis within susceptible individuals.

PMID- 30219210
TI  - Reasons for Young Adult Waterpipe Use in Wave 1 (2013-2014) of the Population
      Assessment of Tobacco and Health Study.
AB  - INTRODUCTION: Waterpipe use is common among U.S. young adults (aged 18-24 years),
      with estimates considerably higher than other age groups. Although studies have
      examined attitudes and beliefs associated with waterpipe use, no study has
      examined reasons for use in a nationally representative sample. METHODS: Using
      latent class analyses, this study examined subgroups based on self-reported
      reasons for use of past 30-day young adult (aged 18-24 years) waterpipe users
      (n=1,198) from Wave 1 (2013-2014) of the Population Assessment of Tobacco and
      Health Study. Data analyses were conducted in 2017. Covariates included
      sociodemographic characteristics, substance use, and internalizing and
      externalizing problems. RESULTS: A three-class model was identified: Class 1
      (socializing and flavors, 57%), Class 2 (many reasons [flavors, socializing, less
      harmful than cigarettes, and affordability], 20%), and Class 3 (socializing,
      23%). Class 3 was considered the referent group. Compared with non-Hispanic
      whites, non-Hispanic blacks were less likely to belong to Class 1, whereas
      Hispanics were more likely to belong to Class 2. Compared with less than high
      school education, greater than high school education was associated with
      membership in Class 1; however, high school graduation was associated with
      membership in Class 2. Past-year alcohol users compared with non-users were less
      likely to belong to Class 2. Past 30-day poly-tobacco users compared with non
      users were more likely to belong to Class 2. CONCLUSIONS: This study revealed
      distinct classes of waterpipe users based on self-reported reasons for use.
      Findings inform targeted policies for waterpipe tobacco control as part of public
      health efforts to mitigate harms associated with tobacco use.

PMID- 30219211
TI  - Rapid Expansion of the Opioid Ecosystem: National Implications for Prescriber
      Pharmacist Communication.

PMID- 30219212
TI  - Opioid Prescribing by Specialty and Volume in the U.S.

PMID- 30219213
TI  - Vulnerability in Heart Failure.

PMID- 30219214
TI  - "Will You Remember Me?": Talking with Adolescents About Death and Dying.
AB  - This article describes the preparation, rationale, and benefits of talking with
      adolescents who have life-threatening or life-limiting illness about advance care
      planning (ACP) and end-of-life concerns in a developmentally sensitive manner.
      The first step is to ensure that a health care provider is ready to work with
      adolescents in ACP discussions by taking a self-inventory, learning communication
      skills, and understanding individual barriers. The authors then outline how to
      assess patient and family readiness, including developmental, cultural, personal,
      and psychosocial considerations. Evidence-based techniques for respectfully and
      productively engaging adolescents in ACP conversations are discussed.

PMID- 30219215
TI  - Supporting Children and Families at a Child's End of Life: Pediatric Palliative
      Care Pearls of Anticipatory Guidance for Families.
AB  - Mental health professionals can play a key role in helping pediatric patients and
      their families prepare for and endure the death of a child. Impactful
      interventions include assisting a family's transition toward acceptance of a
      child's pending death, using prognostication as a tool in emotional preparedness,
      and education on expectant symptoms to optimize management and sense of caregiver
      efficacy.

PMID- 30219216
TI  - Ethical Issues Around Pediatric Death: Navigating Consent, Assent, and
      Disagreement Regarding Life-Sustaining Medical Treatment.
AB  - Decisions regarding whether or not to pursue experimental therapies or life
      sustaining medical treatment of children with life-limiting illness can be a
      significant source of distress and conflict for both families and health care
      providers. This article reviews the concepts of parental permission (consent),
      assent, and emerging capacity and how they relate to decision-making for minors
      with serious illness. Decision-making capacity for adolescents is discussed
      generally and in the context of emotionally charged situations pertaining to the
      end of life. Strategies for minimizing conflict in situations of disagreement
      between children and families are provided.

PMID- 30219217
TI  - Children's Artwork: Its Value in Psychotherapy in Pediatric Palliative Care.
AB  - Pediatric palliative care is a comprehensive treatment approach (physical,
      psychological, social, spiritual) for children living with life-threatening
      conditions. These patients and siblings, as well as children of ill parents, face
      extraordinary psychological challenges. Structured art techniques incorporated
      into psychotherapy can be powerful for children dealing with life-and-death
      realities. This article provides the rationale, instructions, and examples for 3
      techniques that the author has adapted for children facing illness and
      bereavement. Although these art techniques are simple to administer, they
      frequently evoke complex and powerful responses and thus are intended for use by
      or in consultation with mental health professionals.

PMID- 30219218
TI  - Parenting with a Life-Limiting Illness.
AB  - Parents with life-threatening illness face unique challenges in their dual roles
      as patients and parents. They are at risk for depression, parenting stress, and
      impaired family functioning, and their children are at risk for adjustment
      difficulties. In addition to treatment of depression and other mental health
      issues, patients may also benefit from evidence-informed guidance addressing the
      challenges of parenting while ill. Consultations should be tailored to each
      family, with consideration of children's developmental stage and temperament.
      Clinical recommendations for communication about a parent's anticipated death,
      helping children spend meaningful time with an ill parent, and legacy leaving are
      provided.

PMID- 30219219
TI  - Bereavement After a Child's Death.
AB  - The death of a child is a heart-wrenching experience that can have a significant
      impact on parents, siblings, and families while also often having ripple effects
      throughout the child's community. Pediatric loss has an impact on family
      structure and dynamics, individual identity formation, and conceptualization as
      well as professional practice. This article explores bereavement after a child's
      death through the lens of the family, the parent, the sibling, the forgotten
      grievers, and the provider.

PMID- 30219220
TI  - The "Liaison" in Consultation-Liaison Psychiatry: Helping Medical Staff Cope with
      Pediatric Death.
AB  - Pediatric consultation-liaison clinicians are well positioned to provide support,
      guidance, and systemic recommendations about how to help medical clinicians cope
      with the stresses of working with dying children. Interventions to support
      sustainability in this work need to occur at the institutional and team-based
      levels as well as in individual practice. Shared clinical work around challenging
      cases provides opportunities to engage with medical clinicians about their
      difficult experiences and provide reflection and support. Psychiatry services may
      also be in a role of advocating for institutionally based interventions that can
      help their medical colleagues.

PMID- 30219221
TI  - Social Media Consequences of Pediatric Death.
AB  - Social media is an important access point for engagement of children and
      adolescents. For individuals with a life-limiting illness or serving as the
      caregiver for an ill child, social media can be a helpful outlet for support and
      information gathering. It has democratized the process of being remembered
      through providing an ongoing account of thoughts, pictures, and videos that
      theoretically live on forever via a digital legacy. Providers should be familiar
      with how this new generation uses social media during their illness, after death,
      and in the bereavement process.

PMID- 30219222
TI  - Assisting the School in Responding to a Suicide Death: What Every Psychiatrist
      Should Know.
AB  - When a child or adolescent dies by suicide, many individuals are affected, most
      of whom are attending school. Child and adolescent psychiatrists can be called on
      during the wake of such tragic events in order to help schools navigate the
      difficult tasks following a student suicide. Being familiar with suicide
      postvention guidelines is crucial for anyone involved in managing the events
      following a student suicide. By understanding the tenets of suicide postvention
      and resources that are available to schools and clinicians, the tragedy of
      suicide can also be an opportunity to improve school mental health and suicide
      prevention.

PMID- 30219223
TI  - Clinician Response to a Child Who Completes Suicide.
AB  - Although suicide is a leading cause of death for children and adolescents, there
      is a dearth of literature on clinician responses to suicides in that age group.
      However, most psychiatrists experience the death of a patient by suicide, with
      resulting grief reactions including shock, isolation, rumination, self-doubt, and
      impact on clinical decision making. The impact is more pronounced in trainee
      clinicians. Postvention is the clinical, administrative, legal, and emotional
      processes following a suicide. These processes are discussed in detail, with
      recommendations for policies and training that assist clinicians with this
      tragic, but common, professional crisis.

PMID- 30219224
TI  - Dealing with Death and Dying.

PMID- 30219225
TI  - Making Meaning After the Death of a Child.
AB  - Two bereaved mothers recount how they made meaning after the deaths of their
      children, recounting how opportunities to tell their stories in medical settings
      enabled them to construct narratives that promoted resilience and a sense of
      control. Pediatric palliative care can be conceived as opening space for patients
      and guardians to tell their stories outside of the specifics of illness, so
      medical teams can work to accommodate families' values and goals, thereby
      initiating the process of meaning making. Viewing videos of parent stories
      enables medical trainees to enhance their communications skills, empathy, and
      compassion.

PMID- 30219226
TI  - Effects of polarized and non-polarized red-light irradiation on proliferation of
      human Wharton's jelly-derived mesenchymal cells.
AB  - Light emitting diode (LED) irradiation has recently been introduced as an
      encouraging strategy for promotion of cell proliferation. Human umbilical cord
      Wharton's jelly-derived mesenchymal (hUCM) cells are among the most available
      mesenchymal cells with a promising application in regenerative medicine. The aim
      of the present study was to examine the effect of polarized (PL) and non
      polarized (NPL) red-light emitted by LED on various proliferation properties of
      hUCM cells. Cell proliferation was assessed 48 h after irradiation of hUCM cells
      by different energy densities. Cell density increased to a significant level both
      in PL and NPL irradiation at 0.954 J/cm2 following WST-1 assay. Staining of
      irradiated and non-irradiated cells with Hoechst after 3 and 6 days revealed an
      increased proliferation rate in irradiated cells, but the non-irradiated cells
      proliferated more than irradiated cells at day 9 of cultivation. Similar results
      were obtained in trypan blue assay. Scratch repair test for 18 h with an interval
      of 6 h did not reveal a significant difference between irradiated and non
      irradiated cells. In addition, CFU-F assay in PL irradiated cells was higher than
      control when 500 cells/plate was cultivated. Totally, this study revealed that
      hUCM cells could be induced to achieve higher number of cells by PL and NPL red
      light irradiation after 48 h.

PMID- 30219227
TI  - Gulo regulates the proliferation, apoptosis and mesenchymal-to-epithelial
      transformation of metanephric mesenchyme cells via inhibiting Six2.
AB  - During kidney development, the balance between self-renewal and differentiation
      of metanephric mesenchyme (MM) cells, mainly regulated by Sine oculis-related
      homeobox 2 (Six2), is critical for forming mature kidney. L-gulono-gamma-lactone
      oxidase (Gulo), a crucial enzyme for vitamin C synthesis, reveals a different
      expression at various stages during kidney development, but its function in the
      early renal development remains unknown. In this work, we aim to study the role
      of Gulo in MM cells at two differentiation stages. We found that Gulo expression
      in undifferentiated MM (mK3) cells was lower than in differentiated MM (mK4)
      cells. Over-expression of Gulo can promote mesenchymal-to-epithelial
      transformation (MET) and apoptosis and inhibit the proliferation in mK3 cells.
      Knock-down of Gulo in mK4 cells made its epithelial character cells unstabilized,
      facilitated the proliferation and restrained the apoptosis. Furthermore, we found
      that Six2 was negatively regulated by Gulo, and over-expression or knock-down of
      Six2 was able to rescue partially the MET, proliferation and apoptosis of MM
      cells caused by Gulo. In conclusion, these findings reveal that Gulo promotes the
      MET and apoptosis, and inhibits proliferation in MM cells by down-regulating
      Six2.

PMID- 30219228
TI  - miR-1306-3p targets FBXL5 to promote metastasis of hepatocellular carcinoma
      through suppressing snail degradation.
AB  - This study aimed to elucidate the effect of miR-1306-3p on metastasis of
      hepatocellular carcinoma (HCC) and potential mechanism involved. miR-1306-3p
      promoted migration and invasion of HCC in vivo and in vitro. Moreover, miR-1306
      3p inhibited snail to enhance its expression via directly targeting FBXL5, thus
      inducing the epithelial-mesenchymal transition (EMT) in HCC. Intriguingly, miR
      1306-3p expression was transcriptionally enhanced by FoxM1. Consistently, miR
      1306-3p was upregulated in HCC compared with paracarcinoma and correlated with
      poor prognosis of HCC patients. Our researches suggest that miR-1306-3p is a
      tumor enhancer in regulating of HCC metastasis, and miR-1306-3p may be clinically
      utilized as a factor for the clinical diagnosis and prognosis of HCC.

PMID- 30219229
TI  - PPARgamma provides anti-inflammatory and protective effects in intrahepatic
      cholestasis of pregnancy through NF-kappaB pathway.
AB  - AIMS: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific hepatic
      disorder with potentially deleterious consequences of fetuses. Although the
      intimate relationship between ICP and peroxisome proliferator-activated receptor
      gamma (PPARgamma) has been previously reported in physiological and pathological
      conditions, the detailed mechanisms in the process of intrahepatic cholestasis of
      pregnancy has been unclear. The aims of this study are to assess the role of
      PPARgamma regulating the reactive oxygen species (ROS) and inflammation in the
      process of the ICP. METHODS: Clinical data of the pregnant women were collected.
      And the serum of cytokines, hepatic function, the expression of PPARgamma and NF
      kappaB were measured. The rat and fetal rat ICP model were constructed and
      detection of the expression of PPARgamma and NF-kappaB, evaluation the level of
      ROS and inflammation. RESULTS: The clinical data showed that the new-born
      information in severe ICP group were significantly different as compared to that
      in control group (P < 0.05), and part of information in mild ICP group were also
      difference to that in control group (P < 0.05). The expression of PPARgamma and
      NF-kappaB were significantly higher in clinical pregnant women, rat, fetal rat
      ICP model groups and taurocholate acid (TCA) treated HTR-8/SVneo cell (P < 0.01).
      PPARgamma inhibited the production of ROS and decreased the level of
      inflammation. PPARgamma down-regulated the NF-kappaB pathway. CONCLUSIONS:
      PPARgamma provides the anti-inflammatory and protective effects in intrahepatic
      cholestasis of pregnancy through NF-kappaB pathway, which might be a probably one
      of the mechanisms of ICP.

PMID- 30219230
TI  - Vaccination with a DNA vaccine encoding CD317-targeting HBs antigen elicits
      enhanced immunity in mice.
AB  - BACKGROUND: Conventional hepatitis B virus (HBV) vaccines fail to induce
      protective antibody titers in 5-10% of immune-competent vaccines. Therefore, safe
      and effective HBV vaccines are still clinically needed. METHODS: In this study,
      we developed a plasmid DNA vaccine encoding CD317 single-chain fragment variable
      (alpha317scFv) linked with the hepatitis B surface antigen (HBsAg) and detected
      the humoral and cellular immune responses elicited by this vaccine in BALB/c
      mice. RESULTS: Vaccination with this fusion DNA vaccine in BALB/c mice induced
      more robust antiviral T cell and antibody immunity against HBsAg. Compared with
      mice vaccinated with control vaccine encoding HBsAg, the level of serum
      circulating anti-HBsAg antibody (HBsAb) was nearly double in fusion DNA
      vaccinated mice. More interesting, splenic lymphocytes isolated from fusion DNA
      vaccinated mice showed more potent proliferation and IFN-gamma production after
      being re-stimulated with recombinant HBsAg in vitro. And not only that, the
      cytotoxicity of fusion DNA vaccine-sensitized splenocytes was ~3-fold higher than
      that of controls. CONCLUSION: Taken together, our results reveal that the fusion
      DNA vaccine can induce more effective immunological protection against HBV, and
      is a promising candidate for preventing HBV infection.

PMID- 30219231
TI  - Necrostatin-1 ameliorates adjuvant arthritis rat articular chondrocyte injury via
      inhibiting ASIC1a-mediated necroptosis.
AB  - Necroptosis, a necrotic cell death pathway regulated by receptor interacting
      protein (RIP) 1 and 3, plays a key role in pathophysiological processes,
      including rheumatoid arthritis (RA). However, whether necroptosis is involved in
      RA articular cartilage damage processes remain unclear. The aim of present study
      was to investigate the dynamic changes in arthritic chondrocyte necroptosis and
      the effect of RIP1 inhibitor necrostatin-1 (Nec-1) and acid-sensing ion channels
      (ASICs) inhibitor amiloride on arthritic cartilage injury and acid-induced
      chondrocyte necroptosis. Our results demonstrated that the expression of RIP1,
      RIP3 and mixed lineage kinase domain-like protein phosphorylation (p-MLKL) were
      increased in adjuvant arthritis (AA) rat articular cartilage in vivo and acid
      induced chondrocytes in vitro. High co-expression of ASIC1a and RIP1 showed in AA
      rat articular cartilage. Moreover, Nec-1 and amiloride could reduce articular
      cartilage damage and necroinflammation in AA rats. In addition, acid-induced
      increase in necroptosis markers RIP1/RIP3 were inhibited by Nec-1, ASIC1a
      specific blocker psalmotoxin-1 (PcTx-1) or ASIC1a-short hairpin RNA respectively,
      which revealed that necroptosis is triggered in acid-induced chondrocytes and
      mediated by ASIC1a. These findings indicated that blocking ASIC1a-mediated
      chondrocyte necroptosis may provide potential therapeutic strategies for RA
      treatment.

PMID- 30219232
TI  - MicroRNA-613 promotes colon cancer cell proliferation, invasion and migration by
      targeting ATOH1.
AB  - The aim of the present study is to investigate the expression and function of miR
      613 in colon cancer (CC) and illuminate the molecular mechanisms underlying miR
      613-regulated CC progression. Our data demonstrated that miR-613 was upregulated
      in CC tissue samples (P = 0.009) and human CC cell lines (HCT-116 and Lovo; P =
      0.001 and P = 0.003, respectively), which also promoted the proliferation,
      invasion and migration of CC cells (P < 0.05). The dual-luciferase reporter assay
      confirmed that Atonal homolog1 (ATOH1) was the target mRNA of miR-613. Rescue
      experiments showed that ATOH1 overexpression vector significantly reversed the
      stimulative effects of miR-613 mimic on the progression of HCT-116 and Lovo cells
      (P < 0.001). Positive ATOH1 expression in CC tissues was significantly associated
      with lower grade (chi2 = 3.592, P = 0.043), lower TNM stage (chi2 = 3.537, P =
      0.048) and better overall survival (P=0.041). Jun N-terminal kinase 1 (JNK1)
      pathway and Mucin 2 (MUC2) were the potential downstream proteins of miR
      613/ATOH1. miR-613 is an oncogene in CC and promotes the proliferation, invasion
      and migration of CC cells by targeting ATOH1 likely via activating JNK1 pathway
      and upregulating MUC2.

PMID- 30219233
TI  - Prevention of acute liver injury by suppressing plasma kallikrein-dependent
      activation of latent TGF-beta.
AB  - Acute liver injury (ALI) is highly lethal acute liver failure caused by different
      etiologies. Transforming growth factor beta (TGF-beta) is a multifunctional
      cytokine and a well-recognized inducer of apoptotic and necrotic cell death in
      hepatocytes. Latent TGF-beta is activated partly through proteolytic cleavage by
      a serine protease plasma kallikrein (PLK) between the R58 and L59 residues of its
      propeptide region. Recently, we developed a specific monoclonal antibody to
      detect the N-terminal side LAP degradation products ending at residue R58 (R58
      LAP-DPs) that reflect PLK-dependent TGF-beta activation. This study aimed to
      explore the potential roles of PLK-dependent TGF-beta activation in the
      pathogenesis of ALI. We established a mouse ALI model via the injection of anti
      Fas antibodies (Jo2) and observed increases in the TGF-beta1 mRNA level, Smad3
      phosphorylation, TUNEL-positive apoptotic hepatocytes and R58-positive cells in
      the liver tissues of Jo2-treated mice. The R58 LAP-DPs were observed in/around
      F4/80-positive macrophages, while macrophage depletion with clodronate liposomes
      partly alleviated the Jo2-induced liver injury. Blocking PLK-dependent TGF-beta
      activation using either the serine proteinase inhibitor FOY305 or the selective
      PLK inhibitor PKSI-527 or blocking the TGF-beta receptor-mediated signaling
      pathway using SB431542 significantly prevented Jo2-induced hepatic apoptosis and
      mortality. Furthermore, similar phenomena were observed in the mouse model of ALI
      with the administration of acetaminophen (APAP). In summary, R58 LAP-DPs
      reflecting PLK-dependent TGF-beta activation may serve as a biomarker for ALI,
      and targeting PLK-dependent TGF-beta activation has potential as a therapeutic
      strategy for ALI.

PMID- 30219234
TI  - Introduction of an extra tryptophan fluorophore by cataract-associating mutations
      destabilizes betaB2-crystallin and promotes aggregation.
AB  - beta/gamma-Crystallins are predominant structural proteins in vertebrate lens
      with unique properties of extremely high solubility, long-term stability and
      resistance to UV damage. Four conserved Trp residues in beta/gamma-crystallins
      account for UV absorbance and thereafter fluorescence quenching to avoid
      photodamage. Herein we found that betaB2-crystallin Trp fluorescence was greatly
      enhanced by the introduction of an extra unquenched Trp fluorophore by cataract
      associated mutations S31W and R145W. Both mutations impaired oligomerization,
      decreased stability and promote thermal aggregation, while S31W was more
      deleterious. S31W accelerated betaB2-crystallin aggregation under UV damaging
      conditions, whereas R145W delayed. These observations suggested that the
      introduction of an extra Trp fluorophore had complicated effects on betaB2
      crystallin stability and aggregation against various stresses. Our findings
      highlight that the number of Trp fluorophores in beta/gamma-crystallin is
      evolutionarily optimized to exquisitely perform their structural roles in the
      lens.

PMID- 30219235
TI  - Molecularly targeted anti-cancer drugs inhibit the invasion and metastasis of
      hepatocellular carcinoma by regulating the expression of MMP and TIMP gene
      families.
AB  - To investigate the effect of multi-kinase kinase inhibitors (sorafenib;
      regorafenib; lenvatinib) on the invasion and metastasis of human hepatocellular
      carcinoma (HCC) cells, and the outcome of this effect on the expression of matrix
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), yet unclarified.
      Cells were subjected to four different treatments: blank control group, sorafenib
      (10 MUmol/L) treatment group, regorafenib (20 mmol/L) treatment group, and
      lenvatinib (4 MUmol/L) treatment group. Anti-invasion and anti-metastasis effects
      were tested using the wound-healing assay and transwell invasion assay. Real-time
      PCR and Western blot analyses were used to determine the impact of sorafenib,
      regorafenib, and lenvatinib on the gene expression of MMPs and TIMPs in the two
      HCC lines (Hep3B and SMMC-7721). Results from the wound-healing and transwell
      invasion assays showed the three tested anti-cancer drugs to have a significant
      inhibitory effect on the metastasis and invasion of HCC cells. Real-time PCR and
      western blot analyses revealed that sorafenib down-regulated the expressions of
      MMP-7,10,16 and up-regulated those of TIMP-1,3,4, regorafenib down-regulated the
      expression of MMP-1 and up-regulated TIMP-3 gene expression, and lenvatinib down
      regulated the expressions of MMP-1,2,7,9,10,16 and up-regulated those of TIMP
      1,3,4. However, these three targeted anti-cancer drugs seem to have no
      significant regulatory effect on the expressions of other MMPs and TIMPs family
      genes. In conclusion, sorafenib, regorafenib, and lenvatinib inhibit the invasion
      and metastasis of HCC cells by regulating MMPs/TIMPs expression levels.

PMID- 30219236
TI  - Electrospun nanofiber cloud for ultrafast solid phase micro-extraction of trace
      organics in water samples.
AB  - In order to achieve ultrafast solid phase micro-extraction (SPME) of trace
      organics in water samples, the robust polyimide/polyvinylpyrrolidone (PI/PVP)
      composite nanofiber was prepared by electrospinning. Unlike the nonwoven
      electrospun membrane bulk widely used for SPME, the hydrophilic PI/PVP nanofibers
      here can be easily dispersed into and recovered from water sample like a cloud,
      so nanofiber cloud SPME (NC-SPME) was proposed in this work. The extraction
      performance of the NC-SPME method was evaluated using phthalates and
      organochlorine pesticides as model analytes. The extracted analytes were then
      desorbed by acetone and eventually quantified by gas chromatography-mass
      spectrometry (GC-MS). The extraction equilibrium was reached in 30 s for most of
      the phthalates and 2 min for organochlorine pesticides. While for bar-SPME, the
      equilibrium time was much longer than 2 h. At the extraction time of 5 min, the
      recoveries of phthalates and organochlorine pesticides were more than 34% and 52%
      by the NC-SPME method while they were less than 15% and 10% respectively by the
      bar-SPME method. In a word, the NC-SPME method presented significant advantages
      such as fast equilibrium and high recoveries compared to bar-SPME. For the
      phthalates analysis of real samples by NC-SPME, 5 mL of water sample was used for
      a 5-min extraction, linear range covered 1-2 orders of magnitude with correlation
      coefficients (r) higher than 0.99 and limits of detection (LODs) at ng/L levels
      for all of the tested water samples. This method will be useful for the rapid
      micro-extraction of other kinds of organics in water samples even biological
      fluid samples due to the stable composition, ultra-hydrophilic surface of PI/PVP
      nanofiber, and the biocompatible nature of PVP.

PMID- 30219237
TI  - Electron affinities from gas chromatography electron capture detector and
      negative ion mass spectrometry responses and complementary methods.
AB  - The use of the electron-capture detector, ECD, to measure molecular electron
      affinities and kinetic parameters for reactions of thermal electrons with
      molecules at atmospheric pressure separated by chromatography and the sensitive
      and selective quantitative analysis of certain classes molecules are reviewed.
      The evaluated ground state electron affinities of the main group elements and
      diatomic molecules from slightly positive, 0+, to 3.6 eV are summarized. The
      electron affinities of twenty-seven superoxide states determined from pulsed
      discharge ECD and other methods are used to calculate one dimensional potential
      energy curves in agreement with theory. Advances in literature searches have
      uncovered ECD data in dissertations and theses and in the Russian and Japanese
      literature. These data, unpublished radioactive and pulsed discharge ECD thermal
      data from the University of Houston laboratories are used to report and evaluate
      electron affinities. The accuracy and precision of ECD electron affinities of
      organic molecules are identified and tabulated so that they can be added to
      compilations. A procedure for calculating the temperature dependence of electron
      molecule reactions is presented using kinetic and thermodynamic data. These are
      used toselect the most appropriate equipment and conditions for ECD analyses and
      physical determinations.

PMID- 30219238
TI  - Analysis of oncologic and reproductive outcomes after fertility-sparing surgery
      in apparent stage I adult ovarian granulosa cell tumors.
AB  - OBJECTIVE: We evaluated the oncological and reproductive outcomes after fertility
      sparing surgery (FSS) in patients with a stage I adult ovarian granulosa cell
      tumor (AGCT). METHODS: The medical records of patients aged <50 years with a
      stage I AGCT who underwent surgery between January 1983 and April 2017 were
      reviewed. Fertility-sparing surgery was defined as the preservation of the uterus
      and at least one adnexa. Outcomes were compared between groups who underwent FSS
      or radical surgery. Patients who had undergone FSS were contacted to gather
      reproductive outcomes and menstrual histories. RESULTS: A total of 113 patients
      who met the inclusion criteria were included: 61 had FSS while 52 underwent
      radical surgery. After a median follow-up of 99.2 months (range 20.2-394.3
      months), 30 patients had recurrent disease (17 in the FSS group and 13 in the
      radical surgery group). Multivariate analysis showed no difference in disease
      free survival between the groups who underwent FSS or radical surgery (P =
      0.550). In patients who underwent FSS, incomplete staging was significantly
      associated with the risk of recurrence (P = 0.024). Of the 22 patients desiring
      pregnancy, 19 achieved 20 singleton pregnancies. The pregnancy rate was 86.4% and
      the live birth rate was 95%. CONCLUSIONS: FSS is an acceptable option for young
      patients who wish to preserve their fertility. Secondary surgical staging is an
      important treatment in patients with an unstaged AGCT. Reproductive outcomes are
      promising. Radical surgery might be delayed until recurrence, provided they are
      willing to undergo a prolonged follow-up.

PMID- 30219240
TI  - Radiation Dose and Fractionation for Limited-stage Small-cell Lung Cancer: Survey
      of US Radiation Oncologists on Practice Patterns.
AB  - BACKGROUND: Thoracic radiotherapy (TRT) with concurrent chemotherapy is standard
      for limited-stage small-cell lung cancer (LS-SCLC). However, the optimal dosing
      and fractionation remain unclear. The National Comprehensive Cancer Network
      guidelines have recommended either 45 Gy delivered twice daily (BID) or 60 to 70
      Gy delivered once daily (QD). However, the current practice patterns among US
      radiation oncologists are unknown. MATERIALS AND METHODS: We surveyed US
      radiation oncologists using an institutional review board-approved questionnaire.
      The questions covered demographic data, self-rated knowledge of key trials, and
      treatment recommendations. RESULTS: We received 309 responses from radiation
      oncologists. Of the 309 radiation oncologists, 60% preferred TRT QD and 76%
      acknowledged QD to be more common in their practice. The respondents in academic
      settings were more likely to endorse BID treatment by both preference (P = .001)
      and actual practice (P = .009). The concordance between preferring QD and
      administering QD in practice was 100%. In contrast, 40% of respondents who
      preferred BID actually administered QD more often. Also, 15% of physicians would
      be unwilling to switch from QD to BID and 3% would be unwilling to switch from
      BID to QD, even on patient request. Most respondents (88%) recommended a dose of
      45 Gy for BID treatment. For QD treatment, the division was greater, with 54%
      recommending 60 Gy, 30% recommending 63 to 66 Gy, and 10% recommending 70 Gy.
      CONCLUSION: Substantial variation exists in how US radiation oncologists approach
      TRT dosing and fractionation for LS-SCLC. Three quarters of our respondents
      reported administering TRT QD most often. The most common doses were 60 Gy QD and
      45 Gy BID. The results of the present survey have provided the most up-to-date
      information on US practice patterns for LS-SCLC.

PMID- 30219241
TI  - Replicability of exercise programs following bariatric surgery.

PMID- 30219239
TI  - Defining hrHPV genotypes in cervical intraepithelial neoplasia by laser capture
      microdissection supports reflex triage of self-samples using HPV16/18 and
      FAM19A4/miR124-2 methylation.
AB  - OBJECTIVE: HPV16/18 genotyping and detection of hypermethylation of human cell
      genes involved in cervical oncogenesis have shown promising results in triage of
      high-risk HPV (hrHPV)-screen positive women on cervical smears. These tests can
      be performed on self-samples, which contain cervical and vaginal cells. We
      studied whether a self-sample represents the hrHPV type causing the worst
      cervical lesion and whether any differences in hypermethylation of FAM19A4/miR124
      2 exist between CIN lesions caused by different hrHPV types. These results have
      important implications for reflex triage of self-samples. METHODS: Correlation
      between genotype found on self-sample using GP5+/6+-PCR-EIA-LMNX and causative
      hrHPV genotype in the worst lesion on histology was studied using laser capture
      microdissection (LCM)-SPF10-PCR (N = 152). Hypermethylation of FAM19A4/miR124-2
      in the self-sample was tested in a quantitative methylation specific PCR and
      compared between lesions caused by HPV16/18 and other hrHPV genotypes. RESULTS:
      Causative hrHPV genotype of the worst lesion (CIN1, CIN2, CIN3, invasive cervical
      cancer) was detected on self-sample in 93.4%. HPV16 was the most frequently found
      genotype on self-sampling (39.2%, 73/186) and causative genotype in CIN3+ (51.4%,
      38/74, all detected on self-sample). There were no differences in the percentages
      of positive FAM19A4/miR124-2 methylation assays between lesions caused by
      HPV16/18 (73.8% in CIN3+) or other hrHPV genotypes (66.7% in CIN3+) (p = 0.538).
      CONCLUSIONS: Our results show that hrHPV genotypes found on self-sample were a
      good representation of hrHPV in the worst CIN lesion and that methylation testing
      on self-sample for detection of CIN3+ was not significantly different between
      lesions caused by HPV16/18 and other hrHPV genotypes.

PMID- 30219242
TI  - Control of air-breathing in fishes: Central and peripheral receptors.
AB  - This review considers the environmental and systemic factors that can stimulate
      air-breathing responses in fishes with bimodal respiration, and how these may be
      controlled by peripheral and central chemoreceptors. The systemic factors that
      stimulate air-breathing in fishes are usually related to conditions that increase
      the O2 demand of these animals (e.g. physical exercise, digestion and increased
      temperature), while the environmental factors are usually related to conditions
      that impair their capacity to meet this demand (e.g. aquatic/aerial hypoxia,
      aquatic/aerial hypercarbia, reduced aquatic hidrogenionic potential and
      environmental pollution). It is now well-established that peripheral
      chemoreceptors, innervated by cranial nerves, drive increased air-breathing in
      response to environmental hypoxia and/or hypercarbia. These receptors are, in
      general, sensitive to O2 and/or CO2/H+ levels in the blood and/or the
      environment. Increased air-breathing in response to elevated O2 demand may also
      be driven by the peripheral chemoreceptors that monitor O2 levels in the blood.
      Very little is known about central chemoreception in air-breathing fishes, the
      data suggest that central chemosensitivity to CO2/H+ is more prominent in
      sarcopterygians than in actinopterygians. A great deal remains to be understood
      about control of air-breathing in fishes, in particular to what extent control
      systems may show commonalities (or not) among species or groups that have evolved
      air-breathing independently, and how information from the multiple peripheral
      (and possibly central) chemoreceptors is integrated to control the balance of
      aerial and aquatic respiration in these animals.

PMID- 30219243
TI  - Sharp rise in sepsis deaths in the UK.

PMID- 30219244
TI  - Perceived benefits of psychotherapy via telemedicine based on suicide risk
      severity.

PMID- 30219245
TI  - Comparison of short-term oncologic outcome of robotic thyroid surgery using
      dynamic risk stratification: A propensity score-matched comparison study.
AB  - BACKGROUND: The long-term oncologic outcome of robotic surgery for thyroid cancer
      is not well established. The aim of this study was to predict the long-term
      oncologic outcome of robotic surgery by using dynamic risk stratification in
      classic papillary thyroid carcinoma. METHODS: A total of 444 propensity score
      matched pairs of patients with papillary thyroid carcinoma treated with robotic
      surgery and conventional open surgery were classified into 4 response-to-therapy
      categories. The results were compared between the robotic surgery and open
      surgery groups. RESULTS: The median follow-up duration was 60 months. After
      propensity score matching, the robotic surgery group showed less extensive
      thyroid surgery and lymph node dissection and a higher proportion of patients who
      underwent radioactive iodine remnant ablation than the open surgery group;
      however, the dynamic risk stratification did not differ between the 2 groups (P =
      .086). CONCLUSION: The long-term oncologic outcome of robotic surgery is expected
      to be comparable with that of open surgery based on the dynamic risk
      stratification.

PMID- 30219246
TI  - [20-year-old intraretinal foreign body].

PMID- 30219247
TI  - New insights into the complex role of mitochondria in Parkinson's disease.
AB  - New discoveries providing insights into mitochondrial bioenergetics, their
      dynamic interactions as well as their role in cellular homeostasis have
      dramatically advanced our understanding of the neurodegenerative process of
      Parkinson's disease (PD). Respiratory chain impairment is a key feature in
      sporadic PD patients and there is growing evidence that links proteins encoded by
      PD-associated genes to disturbances in mitochondrial function. Against the
      backdrop of latest advances in the development of PD treatments that target
      mitochondria, we aim to give an overview of the literature published in the last
      three decades on the significance of mitochondria in the pathogenesis of PD. We
      describe the contribution of mitochondrial genome alterations and PD-associated
      genes to mitochondrial maintenance. We highlight mitophagy as a key mechanism in
      neurodegeneration. Moreover, we focus on the reciprocal interaction between alpha
      synuclein aggregation and mitochondrial dysfunction. We discuss a novel
      trafficking pathway involving mitochondrial-derived vesicles within the context
      of PD and provide a synopsis of the most recently emerging topics in PD research
      with respect to mitochondria. This includes the relationship between mitochondria
      and cell-mediated immunity, the ER-mitochondria axis, sirtuin-mediated
      mitochondrial stress response and the role of micro RNAs in the aetiology of PD.
      In addition, recent studies have challenged the neuro-centric view of PD
      pathology, moving microglia and astrocytes into the research spotlight. Greater
      insights into these mechanisms may hold the key for the development of novel
      targeted therapies, addressing the need for a disease-modifying treatment, which
      has remained elusive to date.

PMID- 30219248
TI  - Spatial representations in the primate hippocampus, and their functions in memory
      and navigation.
AB  - Hippocampal spatial view neurons in primates respond to the place where a monkey
      is looking, with some modulation by place. In contrast, hippocampal neurons in
      rodents respond mainly to the place where the animal is located. We relate this
      difference to the development of a fovea in primates, and the highly developed
      primate visual system which enables identification of what is at the fovea, and a
      system for moving the eyes to view different parts of the environment. We show
      that the spatial view representation in primates is allocentric, and provide new
      animations using recorded neuronal activity to illustrate this. We also show that
      this spatial representation becomes engaged in tasks in which the location 'out
      there' in a scene of objects and rewards must be remembered. We show that this
      representation of space being viewed provides a framework for the encoding of
      episodic memory and the recall of these memories in primates including humans,
      with hippocampal neurons responding for example in a one-trial object / place
      recall task. These functions of the primate hippocampus in scene-related memory,
      provide a way for the primate hippocampus to contribute to actions in space and
      navigation. We consider in a formal model the mechanisms by which these different
      spatial representations may be formed given the presence of the primate fovea,
      and how these mechanisms may contribute to the representations found during
      navigation in a virtual environment.

PMID- 30219249
TI  - Vital signs changes during different dental procedures: A prospective
      longitudinal cross-over clinical trial.
AB  - OBJECTIVES: The purpose of this study was to evaluate the magnitude of vital
      signs changes during 3 different dental treatments. STUDY DESIGN: A prospective
      longitudinal multiarm cross-over clinical trial was conducted. Three dental
      procedures were performed on each participant: supragingival scaling, dental
      restoration under local anesthesia (LA), and exodontia under LA. The following
      parameters were recorded for in each dental procedure: body temperature (BT),
      respiratory rate (RR), systolic blood pressure (SBP), diastolic blood pressure
      (DBP), mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen
      saturation (SpO2). Three repeated measurements of each parameter were recorded at
      3 phases of each procedure. RESULTS: A total of 150 dental interventions were
      performed on 50 patients. Scaling caused a statistically significant rise in BT,
      RR, and SpO2, and a reduction in HR. Restorative treatment caused a statistically
      significant rise in SpO2 during LA. Exodontia caused a statistically significant
      rise in BT, RR, SBP (during the procedure), and SpO2 (during LA). CONCLUSIONS:
      Scaling and restorative treatment did not significantly impact heart rate. The
      respiratory rate may temporarily rise during LA injection and some dental
      procedures, especially exodontia. Increase in systolic blood pressure and heart
      rate during exodontia was tolerated by healthy patients.

PMID- 30219250
TI  - Non-probabilistic time-variant reliability assessment (NTRA) for the active
      control of vibration systems with convex uncertainties.
AB  - Uncertainties, such as material dispersion, loading fluctuation and cognitive
      inconsistency, widely exist in active vibration control systems, and more
      importantly, the controller performance is generally sensitive to the parametric
      deviation. Thus, the uncertainty-oriented safety assessment for the controlled
      structure is of great significance in practical engineering. In view of the
      limitation of uncertain samples, a novel non-probabilistic time-variant
      reliability assessment (NTRA) approach, which combines the set-theoretical convex
      model and the first-passage method, is proposed for vibration suppression
      problems under the linear quadratic regulator (LQR) control scheme. Boundary
      rules and the time-dependency features of the controlled responses are first
      determined using the space-state transformation and the convex process theory.
      For safety reasons, a new time-variant reliability index is defined under the
      area-ratio principle, and its solution details are further discussed. Two
      engineering examples and one experimental case are presented to demonstrate the
      validity and applicability of the developed methodology.

PMID- 30219251
TI  - Beyond path diagrams: Enhancing applied structural equation modeling research
      through data visualization.
AB  - INTRODUCTION: Structural equation modeling (SEM) is a multivariate data analytic
      technique used in many domains of addictive behaviors research. SEM results are
      usually summarized and communicated through statistical tables and path diagrams,
      which emphasize path coefficients and global fit without showing specific
      quantitative values of data points that underlie the model results. Data
      visualization methods are often absent in SEM research, which may limit the
      quality and impact of SEM research by reducing data transparency, obscuring
      unexpected data anomalies and unmodeled heterogeneity, and inhibiting the
      communication of SEM research findings to research stakeholders who do not have
      advanced statistical training in SEM. METHODS AND RESULTS: In this report, we
      show how data visualization methods can address these limitations and improve the
      quality of SEM-based addictive behaviors research. We first introduce SEM and
      data visualization methodologies and differentiate data visualizations from model
      visualizations that are commonly used in SEM, such as path diagrams. We then
      discuss ways researchers may utilize data visualization in SEM research,
      including by obtaining estimates of latent variables and by visualizing
      multivariate relations in two-dimensional figures. R syntax is provided to help
      others generate data visualizations for several types of effects commonly modeled
      in SEM, including correlation, regression, moderation, and simple mediation.
      DISCUSSION: The techniques outlined here may help spur the use of data
      visualization in SEM-based addictive behaviors research. Using data visualization
      in SEM may enhance methodological transparency and improve communication of
      research findings.

PMID- 30219252
TI  - Is anterolateral ligament rupture a reason for persistent rotational instability
      after anterior cruciate ligament reconstruction?
AB  - BACKGROUND: The aim of the present study was to evaluate the clinical role of
      anterolateral ligament (ALL) rupture and its impact on rotational stability by
      comparing the clinical results and rotational stability between reconstructed
      anterior cruciate ligament (ACL) with intact ALL knees and reconstructed ACL with
      ALL injured knees. METHODS: A total of 69 patients who had undergone surgery for
      ACL reconstruction and had received a minimum of two years of follow-up were
      included. Patients were divided into two groups with respect to the presence of
      ALL rupture on knee magnetic resonance imaging. Patients were assessed
      preoperatively and at final follow-up with physical examination findings and
      functional outcomes. Rotational stability was measured by a non-invasive
      rotameter-like device at the final follow-up at different torque values of 5 Nm
      (newton metres), 10 Nm and 15 Nm, and compared between the two groups. RESULTS:
      The ALL was considered to be ruptured in 45 cases, named Group I (65.2%). The ALL
      was considered to be intact in 24 cases, named Group II (34.8%). No significant
      difference was found between the groups regarding the improvement of the clinical
      scores and physical examination findings (P > 0.05). Group I showed significantly
      higher internal rotation difference compared with Group II in all torque values
      (P < 0.05). CONCLUSION: The difference found on rotational measurement is
      possibly under the value of minimal clinical important difference and does not
      have a clinical effect, therefore ALL reconstruction is not recommended as a
      standard treatment in all patients.

PMID- 30219253
TI  - Diagnostic accuracy of coronary CT angiography performed in 100 consecutive
      patients with coronary stents using a whole-organ high-definition CT scanner.
AB  - AIMS: To evaluate image quality, interpretability, diagnostic accuracy and
      radiation exposure of coronary CT angiography (CCTA) performed with a new scanner
      equipped with 0.23-mm spatial resolution, new generation iterative
      reconstruction, 0.28-second gantry rotation time and intra-cycle motion
      correction algorithm in consecutive patients with coronary stents, including
      those with high heart rate (HR) and atrial fibrillation (AF). MATERIALS AND
      METHODS: We enrolled 100 consecutive patients (85 males, mean age 65 +/- 10
      years) with previous coronary stent implantation scheduled for clinically
      indicated non-emergent invasive coronary angiography (ICA). Image quality,
      coronary interpretability and diagnostic accuracy vs. ICA were evaluated and the
      effective dose (ED) was recorded. RESULTS: Mean HR during the scan was 67 +/- 13
      bpm. Twenty-six patients had >65 bpm HR during scanning and 13 patients had AF.
      Overall, image quality was high (Likert = 3.2 +/- 0.9). Stent interpretability
      was 95.8% (184/192 stents). Among 192 stented segments, CCTA correctly identified
      22 out of 24 with >50% in-stent restenosis (ISR) (sensitivity 92%). In a stent
      based analysis, specificity, positive and negative predictive values and
      diagnostic accuracy for ISR detection were 91%, 99%, 60% and 91%, respectively.
      In a patient-based analysis, CCTA diagnostic accuracy was 85%. Overall, mean ED
      of CCTA was 2.4 +/- 1.2 mSv. CONCLUSIONS: A whole-organ CT scanner was able to
      evaluate coronary stents with good diagnostic performance and low radiation
      exposure, also in presence of unfavorable HR and heart rhythm. TRANSLATIONAL
      ASPECT: The present study is the first to evaluate the CCTA capability of
      detecting in-stent restenosis in consecutive patients, including those with high
      HR and AF, using a recent scanner generation that combines improved spatial and
      temporal resolution with wide coverage. Using the whole-organ high-definition CT
      scanner we obtained high quality images of coronary stents with good
      interpretability and diagnostic accuracy combined with low radiation exposure,
      even in patients with unfavorable HR or heart rhythm for CCTA evaluation.

PMID- 30219254
TI  - Prognostic role of left ventricular ejection fraction in heart failure: Back to
      the future?

PMID- 30219255
TI  - Prevalence and clinical phenotype of concomitant long QT syndrome and
      arrhythmogenic bileaflet mitral valve prolapse.
AB  - BACKGROUND: Mitral valve prolapse (MVP), including the recently described
      arrhythmogenic bileaflet MVP syndrome (ABiMVPS), is associated with
      repolarization abnormalities and may represent an underestimated cause of sudden
      cardiac death. The impact of concomitant MVP or ABiMVPS on long QT syndrome
      (LQTS) clinical severity is unknown. METHODS AND RESULTS: Retrospective review of
      754 LQTS patients [445 females (58%) and mean QTc 471 +/- 41 ms] with available
      echocardiographic data was performed to identify LQTS patients with not only MVP,
      but also a pro-arrhythmic ABiMVPS phenotype defined as bileaflet MVP,
      inferolateral T-wave inversions, and frequent complex ventricular
      ectopy/arrhythmia. As expected, 18/754 (2%) LQTS patients had concomitant MVP. Of
      these, 5/18 (28%) LQTS patients with MVP satisfied ABiMVPS diagnostic criteria.
      No difference in symptomatology, degree of QT prolongation, or clinical
      management was observed between LQTS patients with and without MVP. In contrast,
      LQTS plus ABiMVPS resulted in a severe cardiac phenotype as illustrated by
      symptomatic status (LQTS-ABiMVPS; 5/5; 100%; vs LQTS: 279/736; 39%; p = .008),
      degree of baseline QTc prolongation (LQTS-ABiMVPS: 536 +/- 58 ms; vs LQTS: 470 +/
      40 ms; p = .009), and number of patients experiencing >=1 on-therapy break
      through cardiac event (LQTS-ABiMVPS: 4/5; 80%; vs LQTS: 48/736; 7%; p < .001].
      Lastly, individuals with LQTS plus ABiMVPS were more likely to experience
      appropriate ICD therapies post-cardiac denervation (LQTS-ABiMVPS: 2/3; 67% vs
      LQTS: 4/49; 8%; p = .03]. CONCLUSIONS AND RELEVANCE: The co-existence of LQTS and
      ABiMVPS may lead to a rare, but malignant, clinical entity characterized by
      potentially life-threatening arrhythmias despite maximal LQTS therapy.

PMID- 30219256
TI  - WITHDRAWN: Are high heart rate variability and parasympathetic activity a key for
      wellness?
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 30219257
TI  - Definition, clinical classification and initial diagnosis of pulmonary
      hypertension: Updated recommendations from the Cologne Consensus Conference 2018.
AB  - In the summer of 2016, delegates from the German Society of Cardiology (DGK), the
      German Respiratory Society (DGP), and the German Society of Pediatric Cardiology
      (DGPK) met in Cologne, Germany, to define consensus-based practice
      recommendations for the management of patients with pulmonary hypertension (PH).
      These recommendations were built on the 2015 European Pulmonary Hypertension
      guidelines, aiming at their practical implementation, considering country
      specific issues, and including new evidence, where available. To this end, a
      number of working groups was initiated, one of which was specifically dedicated
      to the definition, clinical classification and initial diagnosis of PH. While the
      European guidelines provide a detailed clinical classification and a structured
      approach for diagnostic testing, their application in routine care may be
      challenging, particularly given the changing phenotype of PH patients who are
      nowadays often elderly and may present with multiple potential causes of PH, as
      well as comorbid conditions. Specifically, the working group addresses the
      thoroughness of diagnostic testing, and the roles of echocardiography, exercise
      testing, and genetic testing in diagnosing PH. Furthermore, challenges in the
      diagnostic work-up of patients with various causes of PH including "PAH with
      comorbidities", CTEPH and coexisting conditions are highlighted, and a modified
      diagnostic algorithm is provided. The detailed results and recommendations of the
      working group on definition, clinical classification and initial diagnosis of PH,
      which were last updated in the spring of 2018, are summarized in this article.

PMID- 30219258
TI  - Interface morphology and gas production by a refractive 347 nm ultraviolet
      femtosecond laser: Comparison with established laser systems.
AB  - PURPOSE: To evaluate gas production and interface quality after refractive
      lenticule creation. A new ultraviolet (UV) 347 nm femtosecond laser was compared
      with the FS200 and the Visumax lasers. SETTING: Department of Anatomy II,
      University of Erlangen-Nurnberg, Erlangen, Germany. DESIGN: Experimental study.
      METHODS: Refractive lenticules were created in 52 porcine corneas with the UV
      laser (n = 20), the Visumax laser (n = 20), and a modified FS200 laser (n = 12).
      Twelve corneas in each laser group were fixed immediately after lenticule
      creation to entrap the gas produced. Lenticule extraction was omitted. From 16
      other corneas (UV and Visumax lasers; n = 8 each) -5.0 diopter (D) and -10.0 D
      lenticules were extracted. On lenticule extraction, a flap was created and
      lifted. In 12 additional corneas, a flap was cut using the FS200 laser and lifted
      afterward; laser in situ keratomileusis was performed on 8 of these samples. The
      corneas were processed for light microscopy (gas bubble 2-dimensional
      morphometry) and scanning electron microscopy (interface quality). RESULTS: The
      Visumax generated approximately one half as much gas as the FS200. The UV laser
      undercut the Visumax by another 50%. The interfaces created by the FS200 appeared
      smooth and without irregularities. The optical zone margin was always conspicuous
      in the Visumax samples but hardly discernible in the UV specimens. Slight
      irregularities and very small lenticule pieces were found occasionally in both
      groups. The UV interfaces appeared slightly rougher than the Visumax interfaces.
      CONCLUSIONS: Ultraviolet laser lenticule extraction seems promising. The
      interface quality was similar to that of the clinical Visumax system while gas
      production was reduced significantly.

PMID- 30219259
TI  - Precision of intraocular lens power prediction in eyes shorter than 22 mm: An
      analysis of 6 formulas.
AB  - PURPOSE: To analyze the precision of 6 intraocular lens (IOL) power calculation
      formulas in predicting refractive outcome in eyes with an axial length (AL) less
      than 22.0 mm. SETTING: Department of Ophthalmology, All India Institute of
      Medical Sciences, Raipur, India. DESIGN: Retrospective observational study.
      METHODS: Patients with an AL less than 22.0 mm were included in the study. If
      both eyes were eligible, a randomly selected eye was chosen. Optical biometry
      with partial coherence interferometry (PCI) was performed in all cases. Six
      formulas were analyzed: Barrett Universal II, Haigis, Hoffer Q, Holladay 2, RBF
      Method and SRK/T. The mean numerical error was defined as the difference between
      the actual postoperative spherical equivalent (SE) at the 1-month follow-up and
      the predicted postoperative SE. The median absolute error was calculated and
      compared between all 6 formulas after the zeroing of the mean numerical error by
      adjusting the lens constant individually for each formula. RESULTS: The study
      comprised 50 eyes of 50 patients. The Friedman test was applied to compare the
      median absolute error between the 6 formulas after the zeroing of the mean
      numerical error. Post hoc analysis and Bonferroni correction for multiple
      comparisons showed no significant statistical difference between them.
      CONCLUSION: The Barrett Universal II, Haigis, Hoffer Q, Holladay 2, RBF method
      and SRK/T formulas were equally accurate in predicting the IOL power in eyes
      shorter than 22.0 mm.

PMID- 30219260
TI  - Attaining the optimal flange for intrascleral intraocular lens fixation.
AB  - We describe a technique for making an optimal flange in intraocular lenses (IOLs)
      used for flanged intrascleral IOL fixation. The flange shape varies in
      poly(methyl methacrylate) (PMMA) haptics of different IOLs of different
      manufacturers. We identified the distance between the forceps grip of the haptic
      and the end of the haptic during heating with a cauter as a critical factor for
      the optimal flange shape in 5 PMMA haptics but not in 2 polyvinylidene fluoride
      haptics.

PMID- 30219261
TI  - Intraoperative optical coherence tomography measurements of aphakic eyes to
      predict postoperative position of 2 intraocular lens designs.
AB  - PURPOSE: To evaluate intraoperative anterior chamber depth (ACD) measurements of
      the aphakic eye to predict the postoperative ACD and compare 2 intraocular lens
      (IOL) designs. SETTING: Hanusch Hospital, Vienna, Austria. DESIGN: Prospective
      study. METHODS: In this prospective study, patients scheduled for cataract
      surgery received a plate-haptic IOL (Asphina, Carl Zeiss Meditec AG) or an open
      loop haptic IOL (ZCB00, Johnson & Johnson). Preoperatively, optical biometry
      (IOLMaster 700, CZM, or Lenstar, Haag-Streit) was performed. Intraoperatively, a
      prototype setup was used to perform time-domain OCT scans of the anterior eye
      segment (Visante connected to OPMI Lumera 200, both CZM). The intraoperative ACD
      was measured and used to predict the postoperative IOL position. Optical biometry
      and subjective refraction and autorefraction (RM 8800, Topcon) were performed 2
      months postoperatively. RESULTS: The study comprised 203 eyes of 203 patients. A
      partial least-square regression model for ACD generated 2 months postoperatively
      showed that the predictive power of the intraoperative ACD (0.48) was highest
      followed by the axial eye length (0.45) and then the preoperatively measured ACD
      (0.30). These findings were confirmed in a bootstrapping model. Regression models
      combining the preoperative ACD and intraoperative ACD resulted in further
      significant improvement. CONCLUSIONS: Intraoperative ACD measurements predicted
      the postoperative position of open-loop IOLs and plate-haptic IOLs better than
      preoperative ACD measurements. Combining preoperative and intraoperative ACD
      measurements further improved the prediction.

PMID- 30219262
TI  - Posttraumatic stress disorder-type behaviors in streptozotocin-induced diabetic
      rats can be prevented by prolonged treatment with vitamin E.
AB  - Anxiety and stress disorders, such as posttraumatic stress disorder (PTSD) have
      been described as debilitating comorbidities of diabetes. In the present study,
      we aimed to investigate anxiety-like behavior and the extinction and
      generalization of aversive memories in fear conditioning using a streptozotocin
      induced model of diabetes (DBT). Moreover, considering that DBT animals present
      increased oxidative stress in brain areas related to anxiety and memory, we aimed
      to evaluate the effect of prolonged treatment with antioxidant vitamin E on
      behavioral parameters of anxiety and fear memory and on the diabetic condition.
      It was observed that DBT animals showed a deficiency in extinguishing the
      aversive memory in a fear conditioning test, along with a generalization of the
      fear memory. They also present a more pronounced anxiety-like behavior in the
      elevated plus maze test. VIT E treatment (300 mg/kg, p.o.) was not able to reduce
      hyperglycemia; however, it was able to block the anxiogenic-like behavior, also
      improving the deficit in the extinction of the aversive memory as well as
      blocking the generalization of such memory in a different context. Taken
      together, our data suggest that DBT animals are prone to extinction deficits and
      generalization of fear memories, behaviors which are observed in models of PTSD.
      Lastly, prolonged VIT E supplementation may be effective in the treatment of
      anxiety, extinction deficit and generalization of fear memories induced by the
      diabetic condition.

PMID- 30219263
TI  - Consolidation of an aversive taste memory requires two rounds of transcriptional
      and epigenetic regulation in the insular cortex.
AB  - The current view of the neurobiology of learning and memory suggests that long
      term memory (LTM) depends not only on the de novo protein synthesis but also on
      the synthesis of mRNA even hours after the acquisition of memory, as well as that
      the regulation of transcription through the histone acetylation is essential for
      the memory establishment. Our previous studies showed that protein synthesis
      inhibition around the time of training and 5-7 hours after acquisition in the
      insular cortex (IC) prevents the consolidation of conditioned taste aversion
      (CTA), a well-established learning and memory paradigm in which an animal learns
      to associate a novel taste with nausea. However, the participation of mRNA
      synthesis and the epigenetic regulation through histone acetylation in this
      process remains unexplored. In the present study we evaluated the effect of the
      inhibition of transcription as well as deacetylation of histones at two temporal
      windows on the consolidation of CTA. Thus, immediately or seven hours after CTA
      acquisition animals received a microinfusion of 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole (DRB) or MS-275 in the IC, respectively. The present
      results show that transcription inhibition immediately and 7 h after acquisition
      impairs the CTA memory consolidation, whereas the inhibition of histone
      deacetylation strengths this memory at those temporal windows. These findings
      reveal that CTA memory requires recurrent rounds of transcriptional modulation
      events in the IC in order to consolidate this memory trace, demonstrating that
      transcriptional and epigenetic modulation substantially contribute to memory
      consolidation-related functions performed by a neocortical area even several
      hours after memory acquisition.

PMID- 30219264
TI  - Non-Contrast Enhanced Magnetic Resonance Angiography: A Modern Alternative for
      Arteriopaths in Renal Failure.

PMID- 30219265
TI  - Bowel Biofilms: Tipping Points between a Healthy and Compromised Gut?
AB  - Bacterial communities are known to impact human health and disease. Mixed species
      biofilms, mostly pathogenic in nature, have been observed in dental and gastric
      infections as well as in intestinal diseases, chronic gut wounds and colon
      cancer. Apart from the appendix, the presence of thick polymicrobial biofilms in
      the healthy gut mucosa is still debated. Polymicrobial biofilms containing
      potential pathogens appear to be an early-warning signal of developing disease
      and can be regarded as a tipping point between a healthy and a diseased state of
      the gut mucosa. Key biofilm-forming pathogens and associated molecules hold
      promise as biomarkers. Criteria to distinguish microcolonies from biofilms are
      crucial to provide clarity when reporting biofilm-related phenomena in health and
      disease in the gut.

PMID- 30219266
TI  - The Application of Thromboelastography in Understanding and Management of
      Ecchymosis After Total Knee Arthroplasty.
AB  - BACKGROUND: Ecchymosis is a common complication after total knee arthroplasty
      (TKA). However, only a few studies have been conducted to determine the
      coagulation status of these patients. Using thromboelastography (TEG), a new
      technique recording the viscoelastic changes of a whole-blood sample, this study
      was performed to understand the ecchymosis-related coagulation status and its
      risk factors. METHODS: Seventy-five patients receiving unilateral TKA were
      recruited in this observational study. Oral rivaroxaban was applied as
      prophylaxis treatment after surgery. TEG was performed 1 day before surgery and 4
      days after surgery. Total blood loss and hidden blood loss were recorded and
      calculated. Univariate and multivariate analyses were conducted to determine risk
      factors. RESULTS: Twenty-five patients (33.3%) developed ecchymosis within 2-3
      days after TKA. Compared with the baseline before TKA, the alpha-angle (P = .032)
      and calculated coagulation index (CI; P = .012) were increased in non-ecchymosis
      group, whereas in the ecchymosis group, there was no significant difference
      regarding any variable of postoperative TEG evaluation. The ecchymosis group
      exhibited more hidden blood loss (P = .007) and total blood loss (P = .011).
      Value change of CI (OR = 0.666, 95% confidence interval = [0.496, 0.895], P =
      .007) and hidden blood loss (OR = 1.008, 95% confidence interval = [1.002,
      1.013], P = .004) were recognized as the independent risk factors for
      postoperative ecchymosis. CONCLUSION: In TEG evaluation, the value change of CI
      and hidden blood loss are independent risk factors of ecchymosis. In view of the
      relative hypocoagulation status, it is reasonable to stop anticoagulation therapy
      in patients with excessive ecchymosis. Personalized anticoagulation therapy may
      be helpful for managing ecchymosis after TKA.

PMID- 30219267
TI  - Overhauser DNP FFC study of block copolymer diluted solution.
AB  - Overhauser dynamic nuclear polarization (DNP) is the dominating hyperpolarization
      technique to increasing the nuclear magnetic resonance signal in liquids and
      diluted systems. The enhancement obtained depends on the overall mobility of the
      radical-carrying molecule but also on its specific interaction with the host
      molecules. Information about the nature of molecular and radical dynamics can be
      identified from determining the nuclear T1 as a function of Larmor frequency by
      Fast Field Cycling (FFC) relaxometry. In this work, DNP and FFC methods were
      combined for a detailed study of 1H Overhauser DNP enhancements at 340 mT (X
      band) and 73 mT (S-band) for diluted solutions of a block-copolymer with and
      without the addition of TEMPO radicals. NMR relaxation dispersions of these
      solutions are measured at thermal polarization and DNP conditions in the X-band,
      and the obtained DNP data were analyzed by a model of electron-nucleus
      interactions modulated by translational diffusion. The coupling factors for the
      two different blocks of the copolymer are obtained independently from DNP and
      NMRD experiments. An additional contribution from scalar interactions was found
      for polystyrene blocks.

PMID- 30219268
TI  - Response to: Towards an integrated functional and epileptological approach in the
      management of meningioangiomatosis.

PMID- 30219271
TI  - The cerebellum seems not a 'little brain' for the autonomic nervous system.

PMID- 30219270
TI  - Exploring the Asian ethnic predisposition to dry eye disease in a pediatric
      population.
AB  - PURPOSE: To investigate the differences in ocular surface characteristics, tear
      film parameters, and dry eye symptomology between co-located pediatric
      populations of Asian and Caucasian ethnicity. METHODS: Seventy New Zealand-born
      pediatric participants, aged between 5 and 18 years, were recruited in an age and
      environmentally controlled cross-sectional study. Participants were classified
      into three groups according to ethnicity and eyelid morphology: Asian single lid
      (ASL), Asian double lid (ADL), and Caucasian double lid (CDL). Ocular biometry,
      tear film parameters, ocular surface characteristics, and dry eye symptomology
      were evaluated in a single clinical session. RESULTS: Overall, no significant
      intergroup differences were observed in tear film quality, dry eye symptomology,
      and meibomian gland dropout. A higher proportion of ASL and ADL participants
      exhibited incomplete blinking than the Caucasian group (both p < 0.001).
      Meibomian gland shortening was more frequently observed among the two Asian
      groups (both p < 0.05), while gland tortuosity was more common in the Caucasian
      group (both p < 0.001). ASL participants exhibited greater inferior lid wiper
      epitheliopathy grades than ADL participants (p = 0.01), and corneal astigmatism
      was more pronounced in the ASL than CDL group (p = 0.02). CONCLUSIONS: Ethnic
      differences in meibomian gland morphological patterns were observed in the
      current pediatric cohort, although overall meibomian gland dropout did not differ
      between groups. Asian participants exhibited a higher degree of incomplete
      blinking, and more marked inferior lid wiper epitheliopathy and corneal
      astigmatism were observed in the ASL group. These findings would suggest that
      eyelid anatomy and tension may potentially be implicated in the development of
      ethnic differences in dry eye disease later in life.

PMID- 30219272
TI  - Handwriting on a tablet screen: Role of visual and proprioceptive feedback in the
      control of movement by children and adults.
AB  - Tablets are increasingly being used in schools for a variety of handwriting
      tasks. Given that the control of handwriting relies on both visual and
      proprioceptive feedback, especially in younger writers, this raises the question
      of whether the texture of the tablet surface affects graphomotor execution. A
      series of recent studies found that when the smoothness of a tablet screen
      modifies proprioceptive feedback, the impact on graphomotor execution varies
      according to the level of the writer's handwriting skills. However, as the
      writing on the screen remained visible in these studies, participants may have
      compensated for the decrease in proprioceptive feedback by relying more heavily
      on visual information. The aim of the present study was therefore to unravel the
      respective contributions of different types of sensory feedback during
      handwriting development and, consequently, the compensatory role of visual
      information when children and adults have to write on a tablet. To this end, we
      asked second and fifth graders and adult participants to write letters and
      pseudowords on a plastic board placed on top of a tablet screen. Participants
      wrote on either the smooth or the granular side of the plastic board
      (manipulation of surface friction), and with normal vision or behind a shield
      that hid the hand and handwriting from direct view (manipulation of vision).
      Kinematic parameters and legibility were recorded to assess handwriting
      performances. Results revealed a significant interaction between proprioceptive
      and visual feedback on letter size, pen speed and legibility, regardless of
      participants' age. Furthermore, reducing the visual and proprioceptive feedback
      had a greater effect on the children's handwriting performances than on those of
      adults. Overall, the present study provides new insight into the contribution of
      the different types of sensory feedback and their interaction with handwriting
      development. In addition, our results on the impact of tablet surface on
      graphomotor execution will serve as useful pointers for improving the design of
      this tool for children, such as increasing the degree of friction of the screen
      surface.

PMID- 30219269
TI  - Comprehensive RNA-Sequencing Analysis in Serum and Muscle Reveals Novel Small RNA
      Signatures with Biomarker Potential for DMD.
AB  - Extracellular small RNAs (sRNAs), including microRNAs (miRNAs), are promising
      biomarkers for diseases such as Duchenne muscular dystrophy (DMD), although their
      biological relevance is largely unknown. To investigate the relationship between
      intracellular and extracellular sRNA levels on a global scale, we performed sRNA
      sequencing in four muscle types and serum from wild-type, dystrophic mdx, and mdx
      mice in which dystrophin protein expression was restored by exon skipping.
      Differentially abundant sRNAs were identified in serum (mapping to miRNA, small
      nuclear RNA [snRNA], and PIWI-interacting RNA [piRNA] loci). One novel candidate
      biomarker, miR-483, was increased in both mdx serum and muscle, and also elevated
      in DMD patient sera. Dystrophin restoration induced global shifts in miRNA
      (including miR-483) and snRNA-fragment abundance toward wild-type levels.
      Specific serum piRNA-like sRNAs also responded to exon skipping therapy. Absolute
      miRNA expression in muscle was positively correlated with abundance in the
      circulation, although multiple highly expressed miRNAs in muscle were not
      elevated in mdx serum, suggesting that both passive and selective release
      mechanisms contribute to serum miRNA levels. In conclusion, this study has
      revealed new insights into the sRNA biology of dystrophin deficiency and
      identified novel DMD biomarkers.

PMID- 30219273
TI  - Fronto-parietal mirror neuron system modeling: Visuospatial transformations
      support imitation learning independently of imitator perspective.
AB  - Although the human mirror neuron system (MNS) is critical for action observation
      and imitation, most MNS investigations overlook the visuospatial transformation
      processes that allow individuals to interpret and imitate actions observed from
      differing perspectives. This problem is not trivial since accurately reaching for
      and grasping an object requires a visuospatial transformation mechanism capable
      of precisely remapping fine motor skills where the observer's and imitator's arms
      and hands may have quite different orientations and sizes. Accordingly, here we
      describe a novel neural model to investigate the dynamics between the fronto
      parietal MNS and visuospatial processes during observation and imitation of a
      reaching and grasping action. Our model encompasses i) the inferior frontal gyrus
      (IFG) and inferior parietal lobule (IPL), regions that are postulated to produce
      neural drive and sensory predictions, respectively; ii) the middle temporal (MT)
      and middle superior temporal (MST) regions that are postulated to process visual
      motion of a particular action; and iii) the superior parietal lobule (SPL) and
      intra-parietal sulcus (IPS) that are hypothesized to encode the visuospatial
      transformations enabling action observation/imitation based on different
      visuospatial viewpoints. The results reveal that when a demonstrator executes an
      action, an imitator can reproduce it with similar kinematics, independently of
      differences in anthropometry, distance, and viewpoint. As with prior empirical
      findings, similar model synaptic activity was observed during both action
      observation and execution along with the existence of both view-independent and
      view-dependent neural populations in the frontal MNS. Importantly, this work
      generates testable behavioral and neurophysiological predictions. Namely, the
      model predicts that i) during observation/imitation the response time increases
      linearly as the rotation angle of the observed action increases but remain
      similar when performing both clockwise and counterclockwise rotation and ii) IPL
      embeds essentially view-independent neurons while SPL/IPS includes both view
      independent and view-dependent neurons. Overall, this work suggests that MT/MST
      visuomotion processes combined with the SPL/IPS allow the MNS to observe and
      imitate actions independently of demonstrator-imitator spatial relationships.

PMID- 30219274
TI  - Immunocryosurgery for non-superficial basal cell carcinomas <= 20 mm in maximal
      diameter: Five-year follow-up.
AB  - OBJECTIVE: To report the five-year follow up results of a prior prospective
      clinical trial (NCT01212562) on immunocryosurgery for the treatment of non
      superficial basal cell carcinoma (BCC) <=20 mm in diameter. MATERIALS AND
      METHODS: Immunocryosurgery consists of five weeks daily 5% imiquimod cream and a
      cryosurgery session on day fourteen. This combination cleared 95 +/- 2% of BCCs
      at the eighteen month follow up. Herein, we present the results of the five year
      follow-up or per last available information of the aforementioned cohort. The
      primary study outcome was treatment failure (non-complete response or relapse);
      failure rates were calculated per intention to treat and per protocol. RESULTS
      AND CONCLUSION: Data for at least five years after initial treatment were
      available for 55% of the patients (53.4% of per protocol treated tumors) as
      actualized up to 31th July 2016. Age at recruitment was the only significant
      predictor of follow-up availability. Nine treatment failures were documented
      after one immunocryosurgery cycle. The five-year tumor free rate after one
      immunocryosurgery cycle was 91.4 +/- 2.8% and 87.7 +/- 3.1% according to per
      protocol and per intention to treat analysis, respectively. Sex, tumor size or
      high-risk anatomical localization within the 'H-area' of the face did not affect
      treatment outcome. With repeat immunocryosurgery cycles only 3 sites were not
      tumor free at last follow up (effectiveness: 97.1 +/- 1.6% per protocol or 93.2
      +/- 2.3% per intention to treat analysis). Immunocryosurgery is an effective,
      minimally invasive treatment alternative to surgical modalities for most BCC <=20
      mm in diameter, including those in high risk localizations.

PMID- 30219275
TI  - Editorial commentary: Cardiometabolic diseases and gut microbiota-removing the
      veil.

PMID- 30219276
TI  - Editorial Commentary: Peripartum cardiomyopathy: Long-term implications of
      treatment and management.

PMID- 30219277
TI  - Delivering all in one: Antigen-nanocapsule loaded with dual adjuvant yields
      superadditive effects by DC-directed T cell stimulation.
AB  - Therapeutic vaccination is and remains a major challenge, particularly in cancer
      treatment. In this process, the effective activation of dendritic cells by a
      combination of distinctly acting adjuvants and an antigen is crucial for success.
      While most common vaccine formulations lack the efficiency to trigger sufficient
      T cell responses in a therapeutic tumor treatment, nanovaccines offer unique
      properties to tackle that challenge. Here, we report the stepwise development of
      a nanocapsule for vaccination approaches, comprising a shell consisting of
      antigen and loaded with a superadditive adjuvant combination. In a first initial
      step, we identified the combination of resiquimod (R848) and muramyl dipeptide
      (MDP) to have a superadditive stimulatory potential. Particulated in Spermine
      modified dextran-nanoparticles, the dual-adjuvant maintains its superadditive
      character and stimulates murine dendritic cells (DC) stronger than the soluble
      equivalents. The second step was to evaluate a protein-based nanocapsule as
      suitable antigen source for the induction of antigen-specific T cell responses.
      Therefore, the DC-mediated antigen-specific T cell proliferation upon treatment
      with nanocapsules, whose shell consists of ovalbumin (OVA), was assessed. At
      least, the superadditive adjuvant combination was encapsulated into OVA
      nanocapsules to create the final nanovaccine. Its immunostimulatory potential for
      DC was extensively tested by measuring the expression of co-stimulatory surface
      markers, the secretion of pro-inflammatory cytokines and the capability to
      mediate OVA-specific T cell responses. The developed nanovaccine triggers strong
      superadditive dendritic cell stimulation and potent antigen-specific CD4+ and
      CD8+ T cell proliferation. Combined with a high modifiability, an excellent
      biocompatibility, low cytotoxicity and an enormous loading capacity, the
      introduced antigen-nanocapsule provides an enormous potential for the effective
      delivery of superadditive adjuvant combinations, particularly when they target
      intracellular receptors.

PMID- 30219278
TI  - Combined encapsulation of a tumor antigen and immune cells using a self
      assembling immunostimulatory DNA hydrogel to enhance antigen-specific tumor
      immunity.
AB  - Our previous study demonstrated that the incorporation of a tumor antigen into a
      self-assembling DNA hydrogel, comprised of a DNA containing un-methylated
      cytosine-phosphate-guanine (CpG) dinucleotides (CpG DNA), efficiently induced
      antigen-specific tumor immunity after intra-tumoral injection into tumor-bearing
      mice. We hypothesized that the additional incorporation of immune cells, the
      target for the antigen and immunostimulatory CpG DNA, would increase the
      antitumor response. To prove this, immune cells were also encapsulated into the
      CpG DNA hydrogel and delivered along with the antigen. Mouse dendritic DC2.4
      cells maintained their form even after incorporation into the DNA hydrogel. The
      incorporation of mouse macrophage-like J774.1 cells and RAW264.7 cells into CpG
      DNA hydrogel did not significantly affect their viability. J774.1, RAW264.7,
      DC2.4, and mouse bone marrow-derived dendritic cells (BMDCs) were efficiently
      activated when incorporated into the CpG DNA hydrogel. The CpG DNA hydrogel
      incorporated with both the tumor antigen and BMDCs effectively induced antigen
      specific immune responses, and retarded tumor growth following intradermal
      administration before and after tumor inoculation without severe local and
      systemic adverse events. These data indicate that the combined delivery of a
      tumor antigen and immune cells using an immunostimulatory CpG DNA hydrogel is
      effective in inducing antigen-specific antitumor immunity.

PMID- 30219279
TI  - Therapeutic inhibition of spleen tyrosine kinase in inflammatory macrophages
      using PLGA nanoparticles for the treatment of non-alcoholic steatohepatitis.
AB  - Non-alcoholic steatohepatitis (NASH) is the leading cause of cirrhosis worldwide
      and the most rapidly growing indication for liver transplantation. Macrophages
      are the important cellular component in the inflammatory milieu in NASH.
      Inflammatory and pro-fibrotic mediators produced by macrophages causes
      significant tissue injury in many inflammatory diseases. Therefore, inhibition of
      the inflammatory macrophages would be a promising approach to attenuate NASH. In
      this study, we studied the implication of SYK pathway in NASH, and investigated
      PLGA nanoparticles-based delivery of SYK pathway inhibitor as an effective and
      promising therapeutic approach for the treatment of NASH. We found positive
      correlation between SYK expression with the pathogenesis of NASH and alcoholic
      hepatitis in patients. Importantly, SYK expression was significantly induced in
      M1-differentiated inflammatory macrophages. To inhibit SYK pathway specifically,
      we used a small-molecule inhibitor R406 that blocks Fc-receptor signaling pathway
      and reduces immune complex-mediated inflammation. R406 dose-dependently inhibited
      nitric-oxide release and M1-specific markers in M1-differentiated macrophages.
      Thereafter, we synthesized PLGA nanoparticles to deliver R406 to increase the
      drug pharmacokinetics for the efficient treatment of NASH. We investigated the
      therapeutic efficacy of R406-PLGA in-vitro in differentiated macrophages, and in
      vivo in Methionine-Choline-deficient (MCD)-diet induced NASH mouse model. R406
      PLGA inhibited M1-specific differentiation markers in RAW and bone-marrow-derived
      macrophages. In-vivo, R406 and more strongly R406-PLGA ameliorated fibrosis,
      inflammation and steatosis in mice. R406 and more significantly R406-PLGA reduced
      ALT, AST, cholesterol and triglyceride plasma levels. These results suggest that
      delivery of SYK inhibitor using PLGA nanoparticles can be a potential therapeutic
      approach for the treatment of Non-alcoholic steatohepatitis.

PMID- 30219281
TI  - Interstitial lung disease: Elementary lesions and diagnosis.
AB  - An effective approach to the diagnosis of interstitial lung diseases requires a
      standardized method of evaluation with a structured analysis, beginning with
      scanning microscopy and proceeding to a more detailed assessment. This article is
      structured around the histologic patterns defined by Leslie that facilitate this
      process. They include acute injury, fibrosis, cellular infiltrates, airspace
      filling, formation of nodules, and minimal changes. Illustrations of all of these
      patterns are provided, together with a discussion of the disease entities that
      manifest them.

PMID- 30219280
TI  - Immune-related Genes to Dominate Neutrophil-lymphocyte Ratio (NLR) Associated
      With Survival of Cetuximab Treatment in Metastatic Colorectal Cancer.
AB  - BACKGROUND: Few clinical studies have investigated the association between
      neutrophil-lymphocyte ratio (NLR) and treatment with cetuximab-based chemotherapy
      in metastatic colorectal cancer (mCRC). The NLR may reflect immune cells
      modulating specific cytokine signals in the tumor microenvironment; however,
      which immune-related genes affect the NLR remain unclear. PATIENTS AND METHODS:
      In 77 patients with KRAS exon2 wild-type mCRC from prospective trials of first
      line chemotherapy with cetuximab, expression levels of 354 immune-related genes
      were measured in tissue samples obtained from all patients by the HTG EdgeSeq
      Oncology Biomarker Panel. The association between the NLR and clinical outcomes
      was evaluated using the Spearman rank correlation coefficient. In addition, 2
      sample t tests were performed to investigate which genes among the top 100 genes
      associated with survival had significantly different expression levels between
      the NLR-low and NLR-high groups among all measured genes. RESULTS: NLR data were
      available for 71 patients. The NLR was associated with progression-free survival
      and overall survival (r = -0.24; P = .040 and r = -0.29; P = .010, respectively).
      When stratified by the median value of the NLR, the Kaplan-Meier curve of NLR-low
      versus NLR-high differed significantly for both progression-free survival
      (median, 11.8 vs. 9.1 months; P = .036) and overall survival (median, 42.8 vs.
      26.7 months; P = .029). The 2-sample t test revealed that the expression levels
      of the LYZ, TYMP, and CD68 genes differed significantly between the NLR-low and
      NLR-high groups (t test P-value < .005; false discovery rate P-value < .15).
      CONCLUSION: NLR is significantly associated with survival in patients with mCRC
      treated with first-line chemotherapy with cetuximab. Genes encoding for
      activities on macrophages may affect the NLR.

PMID- 30219282
TI  - Pest demography critically determines the viability of synthetic gene drives for
      population control.
AB  - Synthetic gene drives offer a novel solution for the control of invasive alien
      species. CRISPR-based gene drives can positively bias their own inheritance, and
      comprise a DNA sequence that is replicated by homologous recombination. Since
      gene drives can be positioned to silence fertility or developmental genes, they
      could be used for population suppression. However, the production of resistant
      alleles following self-replication errors threatens the technology's viability
      for pest eradication in real-world applications. Further, a robust assessment of
      how pest demography impacts the expected progression of gene drives through
      populations is currently lacking. We used a deterministic, two-sex, birth-death
      model to investigate how demographic assumptions affect the efficiency of
      suppression drives for controlling invasive rodents on islands, for two different
      gene-drive strategies. We show that mass-action reproduction results in overly
      optimistic eradication outcomes when compared to the more realistic assumption of
      polygynous breeding. When polygyny was assumed, both gene-strategies failed due
      to the evolution of resistance unless a reproductive Allee effect (reduced
      reproductive rates at low population density) was also included; although model
      outcomes were highly sensitive to the strength of this effect. Increasing the
      size of the initial gene-drive introduction (up to 10% of carrying capacity) had
      little impact on population outcomes. Understanding the demography of a
      population targeted for eradication is critical before the viability of gene
      drive suppression can be adequately assessed.

PMID- 30219283
TI  - Conventional versus minimal ovarian stimulation: an intra-patient comparison of
      ovarian response in poor-responder women according to Bologna Criteria.
AB  - RESEARCH QUESTION: Is minimal ovarian stimulation (MOS) as effective as
      conventional ovarian stimulation (COS) in ovarian response and embryo quality in
      the same 46 poor-responder patients according to the Bologna criteria? DESIGN: An
      intra-patient comparison of patients undergoing both protocols. Ovaries were
      stimulated with either a gonadotrophin-releasing hormone antagonist protocol and
      a combination of recombinant FSH and highly purified human menotrophin (HP-HMG)
      daily (COS), or with the use of clomiphene citrate 50 mg daily and 150 IU of HP
      HMG or recombinant FSH every other day from simulation day 4 (MOS). RESULTS:
      After MOS, significantly more good-quality embryos (1.0 +/- 1.2 versus 0.3 +/-
      0.6) (P = 0.002), oocytes (3.2 +/- 1.9 versus 2.0 +/- 1.8) (P = 0.002), and
      mature (metaphase II) oocytes (2.6 +/- 1.7 versus 1.6 +/- 1.7) (P = 0.001) were
      obtained. In COS cycles, a significantly higher total gonadotrophin dose was
      needed per good-quality embryo (+2194 IU; 95% CI 618 to 3170). CONCLUSIONS: In
      poor responder patients, MOS is a good alternative when COS has failed, or even
      as a first-line treatment. It offered a significantly greater number of good
      quality embryos as well as a higher number of oocytes, using significantly lower
      doses of gonadotrophins per oocyte and embryo obtained.

PMID- 30219284
TI  - Allosteric Effects of the Proton Donor on the Microbial Proton Pump
      Proteorhodopsin.
AB  - Proteorhodopsin (PR) is a microbial proton pump that is ubiquitous in marine
      environments and may play an important role in the oceanic carbon cycle.
      Photoisomerization of the retinal chromophore in PR leads to a series of proton
      transfers between specific acidic amino acid residues and the Schiff base of
      retinal, culminating in a proton motive force to facilitate ATP synthesis. The
      proton donor in a similar retinal protein, bacteriorhodopsin, acts as a latch to
      allow the influx of bulk water. However, it is unclear if the proton donor in PR,
      E108, utilizes the same latch mechanism to become internally hydrated. Here, we
      used molecular dynamics simulations to model the changes in internal hydration of
      the blue variant of PR during photoactivation with the proton donor in protonated
      and deprotonated states. We find that there is a stark contrast in the levels of
      internal hydration of the cytoplasmic half of PR based on the protonation state
      of E108. Instead of a latch mechanism, deprotonation of E108 acts as a gate,
      taking advantage of a nearby polar residue (S61) to promote the formation of a
      stable water wire from bulk cytoplasm to the retinal-binding pocket over hundreds
      of nanoseconds. No large-scale conformational changes occur in PR over the
      microsecond timescale. This subtle yet clear difference in the effect of
      deprotonation of the proton donor in PR may help explain why the
      photointermediates that involve the proton donor (i.e., M and N states) have
      timescales that are orders of magnitude different from the archaeal proton pump,
      bacteriorhodopsin. In general, our study highlights the importance of
      understanding how structural fluctuations lead to differences in the way that
      retinal proteins accomplish the same task.

PMID- 30219285
TI  - Visualizing Tension and Growth in Model Membranes Using Optical Dyes.
AB  - Cells dynamically regulate their membrane surface area during a variety of
      processes critical to their survival. Recent studies with model membranes have
      pointed to a general mechanism for surface area regulation under tension in which
      cell membranes unfold or take up lipid to accommodate membrane strain. Yet we
      lack robust methods to simultaneously measure membrane tension and surface area
      changes in real time. Using lipid vesicles that contain two dyes isolated to
      spatially distinct parts of the membrane, we introduce, to our knowledge, a new
      method to monitor the processes of membrane stretching and lipid uptake in model
      membranes. Laurdan, located within the bilayer membrane, and Forster resonance
      energy transfer dyes, localized to the membrane exterior, act in concert to
      report changes in membrane tension and lipid uptake during osmotic stress. We use
      these dyes to show that membranes under tension take up lipid more quickly and in
      greater amounts compared to their nontensed counterparts. Finally, we show that
      this technique is compatible with microscopy, enabling real-time analysis of
      membrane dynamics on a single vesicle level. Ultimately, the combinatorial use of
      these probes offers a more complete picture of changing membrane morphology. Our
      optical method allows us to remotely track changes in membrane tension and
      surface area with model membranes, offering new opportunities to track
      morphological changes in artificial and biological membranes and providing new
      opportunities in fields ranging from mechanobiology to drug delivery.

PMID- 30219286
TI  - The Development and Enhancement of FRAP as a Key Tool for Investigating Protein
      Dynamics.
AB  - The saga of fluorescence recovery after photobleaching (FRAP) illustrates how
      disparate technical developments impact science. Starting with the classic 1976
      Axelrod et al. work in Biophysical Journal, FRAP (originally fluorescence
      photobleaching recovery) opened the door to extraction of quantitative
      information from photobleaching experiments, laying the experimental and
      theoretical groundwork for quantifying both the mobility and the mobile fraction
      of a labeled population of proteins. Over the ensuing years, FRAP's reach
      dramatically expanded, with new developments in GFP technology and turn-key
      confocal microscopy, which enabled measurement of protein diffusion and
      binding/dissociation rates in virtually every compartment within the cell. The
      FRAP technique and data catalyzed an exchange of ideas between biophysicists
      studying membrane dynamics, cell biologists focused on intracellular dynamics,
      and systems biologists modeling the dynamics of cell activity. The outcome
      transformed the field of cellular biology, leading to a fundamental rethinking of
      long-held theories of cellular dynamism. Here, we review the pivotal FRAP studies
      that made these developments and conceptual changes possible, which gave rise to
      current models of complex cell dynamics.

PMID- 30219288
TI  - Automatic reinforcement from operant wheel-running undermines temporal control by
      fixed-interval schedules of reinforcement.
AB  - The current study compared the development of response patterns for operant wheel
      running and lever-pressing on fixed-interval schedules. Eleven female Long-Evans
      rats were exposed to fixed-interval (FI) 15-s, 30-s, and 60-s schedules with
      wheel revolutions as the operant behavior and sucrose solution as reinforcement.
      Subsequently, a lever was mounted in each wheel and rats responded on an FI-30 s
      schedule of sucrose reinforcement. Operant lever-pressing on average developed a
      scalloping pattern of low responding early in the reinforcement interval followed
      by an increase in pressing to the moment of reinforcement. In contrast, average
      operant wheel-revolutions peaked early in the reinforcement interval followed by
      a plateau, a pattern that did not change over sessions. Variation in the FI
      schedule value (interval size) with operant wheel-running did not alter the
      pattern of running throughout the reinforcement interval, but merely parsed this
      pattern at different points. Cumulative records for the last session showed long
      postreinforcement pauses (PRP) for lever pressing. Wheel running, however, rose
      quickly after reinforcement and continued throughout the reinforcement interval.
      Overall and local wheel-running rates decreased and PRP duration increased as the
      interval size of the FI schedule increased. We propose that the automatic
      reinforcement generated by wheel running, but not lever pressing, provides an
      account of the poor temporal regulation of operant wheel-running in our study.

PMID- 30219287
TI  - Characterization of CTLA4 Trafficking and Implications for Its Function.
AB  - CTLA4 is an essential negative regulator of T-cell immune responses and a key
      checkpoint regulating autoimmunity and antitumor responses. Genetic mutations
      resulting in quantitative defects in the CTLA4 pathway are also associated with
      the development of immune dysregulation syndromes in humans. It has been proposed
      that CTLA4 functions to remove its ligands CD80 and CD86 from opposing cells by a
      process known as transendocytosis. A quantitative characterization of CTLA4
      synthesis, endocytosis, degradation, and recycling and how these affect its
      function is currently lacking. In a combined in vitro and in silico study, we
      developed a mathematical model and identified these trafficking parameters. Our
      model predicts optimal ligand removal in an intermediate affinity range. The
      intracellular CTLA4 pool as well as fast internalization, recovery of free CTLA4
      from internalized complexes, and recycling is critical for sustained
      functionality. CD80-CTLA4 interactions are predicted to dominate over CD86-CTLA4.
      Implications of these findings in the context of control of antigen-presenting
      cells by regulatory T cells and of pathologic genetic deficiencies are discussed.
      The presented mathematical model can be reused in the community beyond these
      questions to better understand other trafficking receptors and study the impact
      of CTLA4 targeting drugs.

PMID- 30219289
TI  - Quantifying compliance and acceptance through public and private social
      conformity.
AB  - Social conformity is a class of social influence whereby exposure to the
      attitudes and beliefs of a group causes an individual to alter their own
      attitudes and beliefs towards those of the group. Compliance and acceptance are
      varieties of social influence distinguished on the basis of the attitude change
      brought about. Compliance involves public, but not private conformity, while
      acceptance occurs when group norms are internalised and conformity is
      demonstrated both in public and in private. Most contemporary paradigms measuring
      conformity conflate compliance and acceptance, while the few studies to have
      addressed this issue have done so using between-subjects designs, decreasing
      their sensitivity. Here we present a novel task which measures compliance and
      acceptance on a within-subjects basis. Data from a small sample reveal that
      compliance and acceptance can co-occur, that compliance is increased with an
      increasing majority, and demonstrate the usefulness of the task for future
      studies of conformity.

PMID- 30219290
TI  - Evaluation of Simulated Lesions as Surrogates to Clinical Lesions for Thoracic CT
      Volumetry: The Results of an International Challenge.
AB  - RATIONALE AND OBJECTIVES: To evaluate a new approach to establish compliance of
      segmentation tools with the computed tomography volumetry profile of the
      Quantitative Imaging Biomarker Alliance (QIBA); and determine the statistical
      exchangeability between real and simulated lesions through an international
      challenge. MATERIALS AND METHODS: The study used an anthropomorphic phantom with
      16 embedded physical lesions and 30 patient cases from the Reference Image
      Database to Evaluate Therapy Response with pathologically confirmed malignancies.
      Hybrid datasets were generated by virtually inserting simulated lesions
      corresponding to physical lesions into the phantom datasets using one projection
      domain-based method (Method 1), two image-domain insertion methods (Methods 2 and
      3), and simulated lesions corresponding to real lesions into the Reference Image
      Database to Evaluate Therapy Response dataset (using Method 2). The volumes of
      the real and simulated lesions were compared based on bias (measured mean volume
      differences between physical and virtually inserted lesions in phantoms as
      quantified by segmentation algorithms), repeatability, reproducibility,
      equivalence (phantom phase), and overall QIBA compliance (phantom and clinical
      phase). RESULTS: For phantom phase, three of eight groups were fully QIBA
      compliant, and one was marginally compliant. For compliant groups, the estimated
      biases were -1.8 +/- 1.4%, -2.5 +/- 1.1%, -3 +/- 1%, -1.8 +/- 1.5% (+/-95%
      confidence interval). No virtual insertion method showed statistical equivalence
      to physical insertion in bias equivalence testing using Schuirmann's two one
      sided test (+/-5% equivalence margin). Differences in repeatability and
      reproducibility across physical and simulated lesions were largely comparable
      (0.1%-16% and 7%-18% differences, respectively). For clinical phase, 7 of 16
      groups were QIBA compliant. CONCLUSION: Hybrid datasets yielded conclusions
      similar to real computed tomography datasets where phantom QIBA compliant was
      also compliant for hybrid datasets. Some groups deemed compliant for simulated
      methods, not for physical lesion measurements. The magnitude of this difference
      was small (<5.4%). While technical performance is not equivalent, they correlate,
      such that, volumetrically simulated lesions could potentially serve as practical
      proxies.

PMID- 30219291
TI  - Common and distinct neural substrates of the money illusion in win and loss
      domains.
AB  - People often evaluate money based on its face value and overlook its real
      purchasing power, a phenomenon known as the money illusion. In the present study,
      using functional magnetic resonance imaging (fMRI) combined with a gambling task,
      we examined the neural signatures of the money illusion in both win and loss
      domains. Behavioral results showed that self-reported satisfaction with outcomes
      was modulated by the face value but not the true value of money in both win and
      loss domains. At the neural level, activity in the posterior insula was
      associated with the true value of money in the win domain, but not in the loss
      domain. Importantly, we found that the ventral striatum, ventromedial prefrontal
      cortex (vmPFC) and amygdala encoded the money illusion in both domains,
      indicating a domain-general rather than domain-specific neural signature.
      Moreover, participants with a larger degree of money illusion at the behavioral
      level showed stronger functional connectivity between the ventral striatum and
      ventral anterior cingulate cortex (vACC) in the win domain, but stronger
      functional connectivity between the ventral striatum and amygdala in the loss
      domain. Our findings highlight the overlapping and distinct neural substrates
      underlying the money illusion in the context of wins and losses.

PMID- 30219292
TI  - Water-exchange MRI detects subtle blood-brain barrier breakdown in Alzheimer's
      disease rats.
AB  - Blood-brain barrier (BBB) breakdown has been hypothesized to play a key role in
      the onset and progression of Alzheimer's disease (AD). However, the question of
      whether AD itself contributes to loss of BBB integrity is still uncertain, as
      many in-vivo studies have failed to detect signs of AD-related BBB breakdown. We
      hypothesize AD-related BBB damage is subtle, and that these negative results
      arise from a lack of measurement sensitivity. With the aim of developing a more
      sensitive measure of BBB breakdown, we have designed a novel MRI scanning
      protocol to quantify the trans-BBB exchange of endogenous water. Using this
      method, we detect increased BBB water permeability in a rat model of AD that is
      associated with reduced expression of the tight junction protein occludin. BBB
      permeability to MRI contrast agent, assessed using dynamic contrast-enhanced
      (DCE)-MRI, did not differ between transgenic and wild-type animals and was
      uncorrelated with occludin expression. Our data supports the occurrence of AD
      related BBB breakdown, and indicates that such BBB pathology is subtle and may be
      undetectable using existing 'tracer leakage' methods. Our validated water
      exchange MRI method provides a new powerful tool with which to study BBB damage
      in-vivo.

PMID- 30219293
TI  - Barriers and Facilitators to Improving Virginia's HPV Vaccination Rate: A
      Stakeholder Analysis With Implications for Pediatric Nurses.
AB  - PURPOSE: Despite the evidence, the availability since 2006, and strong
      recommendations from many professional organizations, the human papillomavirus
      (HPV) vaccine has had a low uptake rate nationally and these trends have been
      even lower in the state of Virginia. DESIGN AND METHODS: We explored key
      stakeholders' perspectives on factors influencing HPV vaccination in central and
      southern Virginia organized within the socio-ecological model (SEM) framework. We
      conducted semi-structured key informant interviews with 31 stakeholders involved
      in HPV vaccination or cancer prevention. RESULTS: Stakeholders identified
      barriers at all SEM levels: Knowledge gaps and sexuality concerns (parent-child
      dyad level), time constraint and inconsistent recommendation (interpersonal
      level), lack of leadership and informational support (organizational and
      community level), and an ineffective mandate (policy level). Facilitators
      identified were realistic/receptive attitude (parent-child dyad level),
      provider's strong recommendation and educational support (interpersonal level),
      team approach and useful data (organizational level), educational outreach and
      community resources (community level), and support from federal and professional
      organizations (policy level). CONCLUSIONS: The stakeholder analysis provided an
      environmental scan of the barriers and facilitators so that an effective HPV
      vaccination strategy can be planned and implemented in the Commonwealth of
      Virginia by public health nurses.

PMID- 30219294
TI  - Improving Asthma Management in the Elementary School Setting: An Education and
      Self-management Pilot Project.
AB  - PURPOSE: To increase daily asthma symptom self-assessments of elementary school
      students using Green Means Go, an asthma education and self-assessment program,
      via a partnership between an elementary school and a school of nursing. METHODS:
      Over four months, accelerated MSN nursing students provided small group education
      sessions to teach students and teachers to identify asthma symptoms by Asthma
      Action Plan (AAP) zones and actions for each zone. To promote continuity of care
      between school and home, a teacher-parent communication log during yellow zone
      days was encouraged. RESULTS: Students with asthma (n = 90), teachers (n = 12)
      and parents (n = 1) participated. Previously no students performed daily self
      assessments and at program end, all students accurately identified symptoms, AAP
      zones, and action steps. A total of 789 symptom self-assessments were recorded.
      Teachers reported increased asthma knowledge. One parent attended an education
      session and one home visit was completed. No communication logs were returned.
      CONCLUSIONS: Partnerships between elementary and nursing schools may be an
      effective strategy for delivery of health programs to high-risk children with
      chronic diseases. Self-assessment of symptoms and taking appropriate actions at
      school are critical components of early asthma intervention, particularly when a
      school nurse is not always available. Training teachers to follow a child's AAP
      within school policies is a critical second step. Home visits showed potential as
      a strategy for engaging parents. PRACTICE IMPLICATIONS: In the current climate of
      school nurse shortages, management of asthma-related episodes in school can be
      improved with similar partnerships and programs that promote health education and
      self-management.

PMID- 30219295
TI  - Severe Obesity in Children May Not Pose Independent Risk for Influenza
      Complications.
AB  - PURPOSE: Subsets of children are targeted for influenza vaccination due to known
      conditions that increase the risk of influenza complications. The purpose of this
      study was to determine if severe obesity in children suggests targeted
      vaccination. DESIGN AND METHODS: A retrospective chart review of a large
      Midwestern pediatric hospital identified 188 cases of influenza complications
      (defined as requiring hospitalization or death) aged 2 to <20 years old from
      August 1, 2010 through June 30, 2013. Severe obesity was defined as body mass
      index (BMI) >=99% for age and gender, with patients grouped by severe obesity
      status (yes vs. no). Cases were reviewed for previously identified risk
      conditions for influenza complications (e.g., asthma, pneumonia, diabetes), and
      were classified as having or not having a known high risk condition. RESULTS: Of
      188 cases, 174 (93%) had a high-risk condition, while only 14 (7%) had no known
      condition. All 14 (100%) with no known high-risk condition had a BMI <99%. All 15
      (100%) with BMI >=99% had a known high-risk condition. The association between
      severe obesity status and influenza complications was not statistically
      significant (p = 0.61). CONCLUSIONS: This suggests that severe obesity in
      children is not an independent high-risk condition for influenza complications
      defined as requiring hospitalization or resulting in death, once other known
      influenza risk factors are considered. IMPLICATIONS: Based on this data,
      clinicians should not target children for influenza vaccination based on weight
      status. We cannot comment about whether severe obesity represents increased risk
      for less severe cases of influenza.

PMID- 30219296
TI  - Community-level Adverse Experiences and Emotional Regulation in Children and
      Adolescents.
AB  - PURPOSE: The association of adverse childhood experiences (ACEs) with negative
      health outcomes is well established, and the concept of allostatic load has been
      proposed as a possible causal mechanism. Most studies measure conventional
      (household) ACE exposures without accounting for non-conventional (community) ACE
      exposures, which may underrepresent the adversity experienced by racial/ethnic
      minorities. We address this gap by calculating the prevalence of both types of
      ACE exposures for racial/ethnic subgroups. We also examine associations of ACE
      exposures and emotional regulation in school aged children and youth. DESIGN AND
      METHODS: This study used data (n = 65,680) for a nationally representative sample
      of children ages 6 to 17 years in the National Survey of Children's Health (2011
      2012). Confirmatory factor analysis, descriptive statistics and regression models
      were used to examine the relationships between ACEs and emotional regulation.
      RESULTS: Community level ACE events disproportionately affect ethnic minorities.
      Some but not all ACEs were significantly and inversely associated with the
      ability to emotionally regulate in children. Experiencing racism had the
      strongest negative effect of all ACE variables. The strength of the child
      caregiver relationship was associated with increased odds of emotional
      regulation, independent of exposure to ACEs. CONCLUSIONS: The study supports the
      need to refine and expand ACE health screenings to fully capture the adversity
      faced by all children. Emotional regulation is identified as a possible
      intervention point. PRACTICE IMPLICATIONS: Expansion of programs that strengthen
      the child-caregiver relationship and reduce ACEs in early childhood may be a key
      approach to increasing coping abilities in youth.

PMID- 30219297
TI  - Association between Pain Sensitivity, Central Sensitization, and Functional
      Disability in Adolescents With Joint Hypermobility.
AB  - PURPOSE: The purpose of this study was to examine the association between pain
      sensitivity, central sensitization, and functional disability in adolescents with
      joint hypermobility. DESIGN AND METHODS: A cross-sectional descriptive design was
      utilized for this study. A sample of 40 adolescents being evaluated for chronic
      pain and autonomic nervous system dysfunction were recruited. Subjects were
      evaluated for pain, function, central sensitization, and sensitivity on pain and
      touch sensory nerve fiber types. Data were analyzed to detect associations
      between variables. RESULTS: Joint hypermobility had a moderately significant
      correlation with central sensitization measured by the Central Sensitization
      Inventory, as well as increased pain sensitivity as evidenced by hypersensitivity
      of Adelta sensory nerve fibers. The presence of central sensitization was also
      positively associated with level of functional disability. CONCLUSIONS: Findings
      implicate joint hypermobility as a possible antecedent to pain hypersensitivity
      and central sensitization syndromes that when recognized and addressed
      effectively may reduce functional disability in those affected. PRACTICE
      IMPLICATIONS: It is important for pediatric nurses that work with adolescents
      that have chronic pain to understand variables that may impact pain and
      functional disability in order to develop methods to increase function, reduce
      pain, and increase perceived quality of life.

PMID- 30219298
TI  - Parents' experiences of Family Centred Care practices.
AB  - PURPOSE: The aim of this study was to gain knowledge and understanding of how
      parents experience Family Centred Care (FCC) using a relatively new tool, and to
      identify aspects of FCC practice for further development. DESIGN AND METHODS: A
      cross-sectional study involving a convenience sample of 48 parents of
      hospitalised children completed a seven-item instrument that measures importance
      and consistency associated with the core aspects of FCC practice, in addition to
      an open-ended question about what does FCC mean to parent. RESULTS: Eighty-five
      percent of parents reported positive experiences of receiving FCC practice from
      nurses, with lower consistency reported in parents' feelings of being seen as
      important in their child's care, feeling valued as a team member, or well cared
      for by nurses. Parents definition of FCC were concise and involved informal
      expressions such as allowing parents to stay with their hospitalised child, and
      family inclusion in child's care and care for the whole family. CONCLUSIONS:
      Although recent FCC debate represent the 'unit of care' in FCC as 'a child within
      the family context', parents' perspectival view of FCC places themselves as care
      recipient with a strong understanding of the ideals of partnership-in-care.
      PRACTICE IMPLICATIONS: Nurses and service providers can use current findings to
      promote the consistent application of Family Centred Care in their everyday
      practice, and to recognise current barriers to the effective implementation of
      Family Centred Care in nursing practice.

PMID- 30219300
TI  - Concept Analysis of Family-Centered Care of Hospitalized Pediatric Patients.
AB  - AIM: The purpose of this concept analysis is to provide a background of family
      centered care of the hospitalized pediatric patient, clarify its components, and
      validate its significance to nursing practice and research. BACKGROUND: The
      concept of family-centered care in the hospital environment has been discussed in
      the literature for over 60 years, yet its principles remain unclear and poorly
      implemented. Further analysis of this concept is warranted and has the potential
      to promote its integration into current nursing practice by increasing awareness
      and clarifying the essential attributes. DATA SOURCES: A systematic review of the
      literature yielded thousands of resources which were narrowed to a comprehensive
      list of 37 sources rich in valuable and applicable content. REVIEW METHODS: This
      analysis utilized the 8-step methodology of concept analysis described by Walker
      and Avant. FINDINGS: The majority of research investigating the concept of family
      centered care and the hospitalized pediatric patient found was focused on
      defining family-centered care and surveying both families and nurses on their
      understanding of the concept. Little research was found exploring the
      relationship of family-centered care with patient and family outcomes, or patient
      and family satisfaction. CONCLUSION: Family-centered care of the pediatric
      patient in the hospital environment remains an abstract concept. It is
      recommended as a cornerstone of modern nursing practice, yet nurses report they
      lack sufficient education regarding its operationalization into practice.
      Elucidation of characteristics coupled with education regarding principles of the
      concept has the potential to augment further integration of family-centered care
      in the hospital environment.

PMID- 30219299
TI  - Centeredness in Healthcare: A Concept Synthesis of Family-centered Care, Person
      centered Care and Child-centered Care.
AB  - BACKGROUND: Increasingly within healthcare, different kind of 'centeredness' are
      used to denote the focus of care which can create confusion for practitioners.
      METHODS: A concept analysis was undertaken to identify the antecedents,
      attributes and relationship between family-, person-, and child-centered care.
      PubMed and CINAHL were searched from 2012 to 2017 and thirty-five papers were
      reviewed. RESULTS: Both person- and child-centered care are focused on
      individuals, a symmetric relationship and the tailoring of care to individual
      needs while family- centered care is focused on the family as a unit of which the
      child is included. Person-centered care focuses on an adult person with autonomy,
      while the focus in child-centered care is the individual child as an own actor
      with rights but still close to a family. CONCLUSION: It appears at a conceptual
      level that the concepts of centeredness contain both similarities and
      differences. Finding ways to structure nursing and focus the care that respects a
      person's dignity and humanity is essential in healthcare and should be a major
      goal of health policy and health systems worldwide. IMPLICATIONS: The
      identification of the antecedents and attributes embedded in the concepts may
      help raise professionals' awareness of the different foci and how this will
      influence one's practice. There is a need to recognize strengths and weaknesses
      of the centeredness in different settings and environments. Furthermore, it is
      important to know which approach to apply within different situations so that
      quality care is enabled for every person, child and family.

PMID- 30219301
TI  - Dietary Intake Among Head Start Preschooler-caregiver Dyads.
AB  - PURPOSE: The purpose of this study was to examine the relationship between Head
      Start preschooler-caregiver dyad's dietary intake and factors influencing dietary
      intake. DESIGN AND METHODS: A cross-sectional, correlational design was used.
      Height and weight were measured. Caregivers completed an online survey assessing
      demographics, dietary intake, feeding practices, and psychosocial factors.
      RESULTS: Seventy dyads, recruited from two urban Head Start centers in the
      Midwestern U.S., participated. The mean age for preschoolers and caregivers was
      3.90 (63% female) and 28.97 years (94% female), respectively. About 43% of
      preschoolers and 81% of caregivers were overweight/obese. Sixty-seven percent of
      caregivers, but only 9% of preschoolers, met the fruit/vegetable (F/V)
      recommendation. Preschoolers' F/V intake was not significantly correlated with
      their caregivers' F/V intake after adjusting for demographics and psychosocial
      factors (B = 0.05, p = .607). Caregiver race (B = -0.71, p = .05), nutrition
      knowledge (B = -0.35, p = .017), perceived caregiver weight (B = -0.85, p =
      .035), perceived child weight (B = 1.09, p = .029), and concerns of preschoolers'
      weight (B = 0.79, p = .004) were significantly correlated with preschoolers' F/V
      intake, after adjusting for demographics, caregiver F/V intake, and other
      psychosocial factors. CONCLUSIONS: The study findings indicate the critical need
      to improve preschoolers' dietary intake and the important influence of caregivers
      on their preschoolers' dietary intake. Given the few limitations of the study
      (e.g., small sample size, food frequency questionnaire), interpretation and
      application of the study's findings warrant caution. PRACTICE IMPLICATIONS:
      Pediatric practitioners and researchers need to design effective programs to
      improve low-income Head Start preschoolers' dietary intake, thereby helping to
      curb the current childhood obesity epidemic.

PMID- 30219302
TI  - Maturity in Adolescents with Type 1 Diabetes Mellitus: A Concept Analysis.
AB  - THEORETICAL PRINCIPLES: The transition from adolescence to adulthood can be a
      particularly challenging time for teenagers with type 1 diabetes mellitus (T1DM).
      Adolescents with T1DM must manage a treatment regimen which requires a high level
      of responsibility and self-care. Often the responsibilities of self-care are
      given to these teens without a clear assessment of their maturity, resulting in
      poor health outcomes. In order to accurately assess a youth's ability to assume
      self-management of T1DM, a clear understanding of the concept of maturity is
      needed. PHENOMENA ADDRESSED: The purpose of this paper is to provide a
      theoretical definition of the concept of maturity in the context of adolescents
      with T1DM and support this definition based on a literature review. This
      discussion was developed utilizing the Walker and Avant approach to concept
      analysis. RESEARCH LINKAGES: This concept analysis defined maturity in
      adolescents with T1DM as a multi-dimensional state of development that
      encompasses the physical, cognitive, psychological, and social dimensions of
      being. Maturity requires that an individual is capable of functioning with
      behavioral, cognitive, and emotional autonomy in self-care activities related to
      TIDM on a consistent basis. This explanation also emphasizes that the process of
      achieving maturity is gradual and dynamic in nature. Caregivers must understand
      that physical age alone does not indicate that an adolescent is adequately
      prepared to assume independent diabetes management. Nurses are in the unique
      position to assist youth with the transition from dependent diabetes care to
      independent self-management of the disease; thus, increasing the likelihood of
      positive outcomes.

PMID- 30219303
TI  - The Teach Back Project: A System-wide Evidence Based Practice Implementation.
AB  - PURPOSE: Teach-back is an evidence-based strategy identified as a cornerstone
      intervention for improving communication during healthcare encounters. Evidence
      supports the use of teach back with patients and families to improve
      understanding of discharge instructions and supporting self-management. There is
      significant evidence that staff do not routinely use teach-back while
      communicating with patients and families. DESIGN AND METHODS: This evidence-based
      practice project examined the impact of a brief educational intervention for a
      multidisciplinary staff on knowledge of health literacy and the use of teach-back
      during patient-education. Clinical staff working at a 290 bed Magnet(r)
      designated Midwest pediatric healthcare organization attended a 45-60 min,
      standardized, instructor led interactive teaching session about the impact of low
      health literacy, the use of open ended questions and how to use teach-back with
      patients and families. Pre and post education surveys, and a one-year
      sustainability survey were administered. RESULTS: Over 300 multidisciplinary team
      members (including acute care, emergency room, and surgical nurses, dieticians,
      respiratory care practitioners and occupational and physical therapists)
      participated in the education and surveys. Both nurses and non-nurses
      demonstrated increased knowledge of the teach-back process and reported high
      rates of clarifying information and correcting misunderstandings when using teach
      back with patients and families. Qualitative data revealed clarifications are
      often about medications and skill-based treatments. CONCLUSIONS AND PRACTICE
      IMPLICATIONS: Teach-back is a valuable strategy that can improve the safety and
      quality of health care and supports the National Action Plan to Improve Health
      Literacy.

PMID- 30219304
TI  - Customization of the TRU-PBMT App (Technology Recordings to better Understand
      Pediatric Blood and Marrow Transplant).
AB  - PURPOSE: Our investigative team is integrating mobile health technologies into
      pediatric blood and marrow transplant (PBMT) care. We aim to evaluate whether
      patient-generated health data can be used to monitor health status and enhance
      symptom management. While there are numerous health-related apps, none address
      the symptoms or care needs specific to PBMT patients. This article describes
      development of the Technology Recording to better Understand Pediatric Blood and
      Marrow Transplant (TRU-PBMT) mobile application. DESIGN AND METHODS: A one-time
      survey was distributed to PBMT clinicians, caregivers, and outpatients to elicit
      feedback and suggestions for the app's design. RESULTS: Feedback from clinicians
      (n = 23), caregivers (n = 5), and PBMT outpatients (n = 4) indicated the app
      would be acceptable and useable with this group of patients between eight and
      eighteen years of age. Suggestions from respondents included: making the app
      language and graphics more child-friendly; adding symptoms such as fatigue,
      mucositis, bleeding; and a visual stool chart. CONCLUSION: Patient, caregiver,
      and clinician feedback was valuable in creation of the TRU-PBMT app. We designed
      a pediatric friendly, PBMT-symptom-specific app, which we will test in future
      studies. IMPLICATIONS FOR PRACTICE: This app facilitates patient-generated health
      data collection and informs health care plans.

PMID- 30219306
TI  - Immunizations: A Coherent Mission and Vision for Pediatric and Child Health
      Nursing Practice, Education, Research and Policy.

PMID- 30219305
TI  - Obesity Prevention Behaviors in Asian Indian Adolescent Girls: A Pilot Study.
AB  - PURPOSE: The purpose of this pilot study was to evaluate obesity prevention
      behaviors of Asian Indian adolescent females and determine the relationship of
      these behaviors to cardiovascular risk factors. DESIGN AND METHODS: A purposive
      sample of twenty females, 14-18 years of age, was enrolled. Body mass index,
      percent body fat, waist circumference, and blood pressure were measured to assess
      cardiovascular risk. Measures of obesity prevention behaviors were physical
      activity, dietary and sleeping behaviors. To quantify engagement in physical
      activity, participants wore an accelerometer. The dietary intake was assessed
      using the web based SuperTracker. Pittsburgh Sleep Quality Index was used to
      assess sleep behaviors. For data analysis, descriptive statistics was used for
      demographic characteristics. Correlations were calculated to evaluate the
      relationship between cardiovascular risk factors and obesity prevention
      behaviors. RESULTS: The majority of the adolescents did not meet recommended
      physical activity levels. Most reported unhealthy eating behaviors with higher
      saturated fat intake correlating with higher percent body fat. The cardiovascular
      risk measures fell below normative values. However, more time spent in sedentary
      behaviors was related to higher systolic blood pressure, while poor sleep quality
      was associated with higher diastolic blood pressure and greater BMI. CONCLUSIONS:
      The findings support the unhealthy patterns of physical activity, dietary and
      sleep behaviors in Asian Adolescent girls and the need for promoting healthy
      behaviors in this at risk population. PRACTICE IMPLICATIONS: The study findings
      provide a basis for education on healthy behaviors and development of culturally
      appropriate interventions to prevent obesity.

PMID- 30219307
TI  - Adjuvant treatments associated with botulinum toxin injection for managing
      spasticity: An overview of the literature.
AB  - BACKGROUND AND OBJECTIVE: A wide range of adjunct therapies after botulinum toxin
      administration have been proposed. The aim of the present paper is to provide an
      overview of major writings dealing with adjuvant (non-pharmacological) treatments
      associated with botulinum toxin for managing spasticity in order to provide some
      up-to-date information about the usefulness of the most commonly used procedures.
      METHODS: The literature in PubMed was searched with the MeSH terms botulinum
      toxins, muscle spasticity, physical therapy modalities, and rehabilitation. The
      results were limited to studies focusing on adjuvant treatments associated with
      botulinum toxin for managing spasticity. We excluded papers on the use of non
      drug treatments for spasticity not associated with botulinum toxin serotype A
      (BoNT-A) injection. Relevant literature known to the authors along with this
      complementary search represented the basis for this overview of the literature.
      RESULTS: Adhesive taping and casting effectively improved the botulinum toxin
      effect in patients with upper- and lower-limb spasticity. There is level 1
      evidence that casting is better than taping for outcomes including spasticity,
      range of motion and gait. However, consensus about their most appropriate timing,
      duration, target and material is lacking. In terms of physical modalities
      combined with botulinum toxin injection, we found level 1 evidence that
      extracorporeal shock wave therapy is better than electrical stimulation for some
      post-injection outcomes including spasticity and pain. Furthermore, electrical
      stimulation of injected muscles might be useful to boost the toxin effect.
      However, the best stimulation protocol has not been defined. In addition, we
      found level 2b evidence that whole-body vibration therapy might reduce spasticity
      with cerebral palsy. CONCLUSION: Future research in this field should focus on
      investigating the most appropriate post-injection treatment protocol for each
      goal to achieve.

PMID- 30219308
TI  - Acquired undescended testis and possibly associated testicular torsion in
      children with cerebral palsy or neuromuscular disease.
AB  - INTRODUCTION: Torsion of an undescended testis (UDT) associated with cerebral
      palsy (CP) and neuromuscular disease (NMD) is an uncommon condition that is not
      well recognized by primary care physicians or healthcare providers. OBJECTIVE:
      The objective of this study was to highlight the clinical importance of torsion
      of a UDT in children with CP and NMD. MATERIALS AND METHODS: Eleven children with
      testicular torsion of a UDT operated on at the study institute between 1991 and
      2015 were identified. The records of seven children (63.6%) associated with CP or
      NMD were retrospectively reviewed. Clinical findings of testicular torsion were
      assessed along with the treatment outcome and testicular salvageability. RESULTS:
      All seven children were not identified with a UDT by public health checkup for
      infant and young children. No children with CP or NMD had torsion of a descended
      testis during the present study period. Median age at surgery was 15 years
      (range, 1-20 years). The testis location was at the external inguinal ring in
      five patients, in the inguinal canal in one, and in the superficial inguinal
      pouch in one. Of the contralateral testes, four were a UDT, one was a retractile
      testis, and two were descended testes. Orchiectomy was performed in six patients
      (85.7%). In the remaining patients, the testis was preserved but became atrophic.
      DISCUSSION: This study demonstrated that children with CP or NMD may be affected
      with torsion of a UDT with peak at around puberty with the poor salvage rate,
      even if the testes appear descended in infancy and young children. Shortcomings
      of this study were the retrospective design and a small series of children
      undergoing surgery for torsion of a UDT. CONCLUSION: Pediatric urologists need to
      educate primary care physicians and healthcare providers in the recognition of
      acquired UDTs and possibly associated testicular torsion in children with CP and
      NMD. Genital examination should be continued regularly until adolescence in these
      children to detect acquired UDT. These children should be referred to pediatric
      urologists to promote surgery as soon as the diagnosis of acquired UDT is carried
      out. It is believed that it is perhaps the best approach to prevent loss of the
      testis in children with CP and NMD.

PMID- 30219310
TI  - Mucosal and Skin Langerhans Cells - Nurture Calls.
AB  - Langerhans cells (LCs) are classically viewed as unique antigen-presenting cells
      (APCs) that originate from embryonic precursors and maintain themselves
      independently in the epidermis. However, recent studies have demonstrated that
      murine LCs in mucosal epithelia arise and are continuously replenished from
      circulating bone marrow (BM) precursors. This has led to the emergence of a novel
      perspective proposing that LCs can evolve from various origins. Because both
      embryonic and BM precursors differentiate into LCs only after entering the
      epithelium, this highlights its crucial role in nurturing LC development to
      perfectly comply with the physiological functions of the tissue. Thus, current
      evidence suggests plasticity of LC differentiation, revealing novel developmental
      mechanisms that are controlled by environmental cues.

PMID- 30219309
TI  - Type III Interferons in Antiviral Defenses at Barrier Surfaces.
AB  - Barrier surfaces such as the epithelium lining the respiratory and
      gastrointestinal (GI) tracts, the endothelium comprising the blood-brain barrier
      (BBB), and placental trophoblasts provide key physical and immunological
      protection against viruses. These barriers utilize nonredundant mechanisms to
      suppress viral infections including the production of interferons (IFNs), which
      induce a strong antiviral state following receptor binding. However, whereas type
      I IFNs control infection systemically, type III IFNs (IFN-lambdas) control
      infection locally at barrier surfaces and are often preferentially induced by
      these cells. In this review we focus on the role of IFN-lambda at barrier
      surfaces, focusing on the respiratory and GI tracts, the BBB, and the placenta,
      and on how these IFNs act to suppress viral infections.

PMID- 30219311
TI  - Diabetes Self-Management Education and Medical Nutrition Therapy: A Multisite
      Study Documenting the Efficacy of Registered Dietitian Nutritionist Interventions
      in the Management of Glycemic Control and Diabetic Dyslipidemia through
      Retrospective Chart Review.
AB  - BACKGROUND: Diabetes self-management education (DSME) and medical nutrition
      therapy (MNT) improve glycemic control and reduce risk of chronic comorbid
      disease. OBJECTIVE: Document outcomes for patients with type 2 diabetes (T2D)
      completing DSME and MNT through American Diabetes Association-recognized
      programs. DESIGN: Descriptive, retrospective chart review. PARTICIPANTS/SETTING:
      Four random samples of 100 records of patients with T2D completing DSME and MNT
      at each of four regional centers in Alabama, June 2013 to 2014, were chosen for
      review; after exclusions, 392 records were retained. OUTCOME MEASURES: Weight,
      body mass index (BMI), hemoglobin A1c (HbA1c), total cholesterol, low-density
      lipoprotein, high-density lipoproteins (HDL), triglycerides (TG), and TG-to-HDL
      ratio. ANALYSIS: Mixed-model analysis of variance was used to determine
      differences between continuous variables. McNemar test was used to assess
      frequency of patients reaching glycemic targets. Paired t tests were used to
      determine significance of lipid parameters. RESULTS: Significant reductions were
      observed at end of program and 1 year in weight (2.67+/-5.54 kg, P<0.001; 2.25+/
      5.45 kg, P=0.001), BMI (0.93+/-1.91, P<0.001; 0.76+/-1.93, P=0.001), and HbA1c
      (1.82%+/-2.23%, P<0.001; 1.22%+/-2.15%, P<0.001). Patients managed by diet alone
      had a mean baseline HbA1c of 6.95% and exhibited a 0.8% reduction in HbA1c
      (P<0.001) at end of program. Those managed with diet plus drug therapy had a
      baseline HbA1c of 9% and exhibited a 2.09% reduction in HbA1c (P<0.001).
      Following DSME and MNT, 62% of patients reached glycemic targets (HcA1c<=7%), as
      compared with 32% at baseline (P<0.001). Significant reductions in TG were
      observed from baseline (162+/-74 mg/dL [4.19+/-1.91 mmol/L]) to follow-up (109+/
      36 mg/dL [2.82+/-0.92 mmol/L]) (P<0.001). HDL increased from baseline (45+/-13
      mg/dL [1.16+/-0.34 mmol/L]) to follow-up (48+/-11 mg/dL [1.24+/-0.28 mmol/L])
      (P=0.05). The TG-to-HDL ratio improved from a baseline of 4.07+/-2.41 to 2.48+/
      1.26 at follow-up (P<0.001). CONCLUSIONS: Reductions were observed in weight,
      BMI, HbA1c, TG, and TG-to-HDL ratio. Improved patient outcomes were achieved in
      the clinical setting and support universal coverage to increase patient access to
      DSME and MNT.

PMID- 30219312
TI  - The effects of antibiotic type and extender storage method on sperm quality and
      antibacterial effectiveness in fresh and cooled-stored stallion semen.
AB  - Two experiments were conducted to evaluate the effects of antibiotic-containing
      extender of on sperm quality and control of bacterial growth. In Experiment 1,
      ejaculates were diluted in extender containing no antibiotics, potassium
      penicillin G-amikacin disulfate (PEN-AMIK), ticarcillin disodium-potassium
      clavulanate (TICAR-CLAV), piperacillin sodium/tazobactam sodium (PIP-TAZ), or
      meropenem (MERO). In freshly extended semen, only slight differences were
      detected among some antibiotic treatments for total sperm motility, curvilinear
      velocity, and viable acrosome-intact sperm (P < 0.05). In cool-stored semen,
      slight differences were also detected among certain antibiotic treatments for
      curvilinear velocity and chromatin integrity (P < 0.05). In Experiment 2,
      ejaculates were diluted in extender and subjected to no bacterial spiking, or
      inoculated with lower or higher doses of K. pneumoniae or P. aeruginosa.
      Following cooled storage of semen, colony forming units/ml (CFU/mL) were less in
      PEN-AMIK (706 +/- 244) and MERO (1576 +/- 1076) treatment groups than in TICAR
      CLAV (4678 +/- 1388) or PIP-TAZ (8108 +/- 3198) treatment groups (P < 0.05). The
      CFU/mL were lower in all antibiotic-containing treatment groups than the control
      group (18478 +/- 4374; P < 0.05). The percentage of culture plates containing no
      bacterial growth in unspiked semen was greater in PEN-AMIK (75%) than PIP-TAZ
      (15%) or TICAR-CLAV (20%; P < 0.05). The percentages of culture plates containing
      no bacterial growth in semen spiked with a lower doses of K. pneumoniae or P.
      aeruginosa were higher in PEN-AMIK (70% and 50%, respectively) then in all other
      treatment groups (0-40% and 0-15% for K. pneumonia and P. aeruginosa,
      respectively; P < 0.05); however, complete control of bacterial load was only
      modest even with PEN-AMIK. In both experiments, freezing and thawing extender
      prior to use did not have any appreciable detrimental effect on sperm quality or
      antibiotic efficacy. In summary, all antibiotics tested had minimal effects on
      measures of sperm quality in fresh or cool-stored semen extenders; however, PEN
      AMIK, followed by MERO, yielded the best results in terms of antimicrobial
      efficacy. None of the antibiotic types controlled bacterial growth, in comparison
      with the antibiotic-free control group, when extended semen was spiked with a
      high concentration of Pseudomonas aeruginosa. Cooled storage of extended semen
      reduced bacterial growth in comparison with freshly extended semen.

PMID- 30219313
TI  - Corrigendum to "Novel molecularly imprinted polymer based on beta
      cyclodextrin@graphene oxide: Synthesis and its application for selective
      diphenylamine determination" [J. Colloid Interface Sci. 503 (2017) 47-56].

PMID- 30219314
TI  - Liver cirrhosis in sub-Saharan Africa: neglected, yet important.

PMID- 30219315
TI  - The increasing burden of diabetes and variations among the states of India: the
      Global Burden of Disease Study 1990-2016.
AB  - BACKGROUND: The burden of diabetes is increasing rapidly in India but a
      systematic understanding of its distribution and time trends is not available for
      every state of India. We present a comprehensive analysis of the time trends and
      heterogeneity in the distribution of diabetes burden across all states of India
      between 1990 and 2016. METHODS: We analysed the prevalence and disability
      adjusted life-years (DALYs) of diabetes in the states of India from 1990 to 2016
      using all available data sources that could be accessed as part of the Global
      Burden of Diseases, Injuries, and Risk Factors Study 2016, and assessed
      heterogeneity across the states. The states were placed in four groups based on
      epidemiological transition level (ETL), defined on the basis of the ratio of
      DALYs from communicable diseases to those from non-communicable diseases and
      injuries combined, with a low ratio denoting high ETL and vice versa. We assessed
      the contribution of risk factors to diabetes DALYs and the relation of overweight
      (body-mass index 25 kg/m2 or more) with diabetes prevalence. We calculated 95%
      uncertainty intervals (UIs) for the point estimates. FINDINGS: The number of
      people with diabetes in India increased from 26.0 million (95% UI 23.4-28.6) in
      1990 to 65.0 million (58.7-71.1) in 2016. The prevalence of diabetes in adults
      aged 20 years or older in India increased from 5.5% (4.9-6.1) in 1990 to 7.7%
      (6.9-8.4) in 2016. The prevalence in 2016 was highest in Tamil Nadu and Kerala
      (high ETL) and Delhi (higher-middle ETL), followed by Punjab and Goa (high ETL)
      and Karnataka (higher-middle ETL). The age-standardised DALY rate for diabetes
      increased in India by 39.6% (32.1-46.7) from 1990 to 2016, which was the highest
      increase among major non-communicable diseases. The age-standardised diabetes
      prevalence and DALYs increased in every state, with the percentage increase among
      the highest in several states in the low and lower-middle ETL state groups. The
      most important risk factor for diabetes in India was overweight to which 36.0%
      (22.6-49.2) of the diabetes DALYs in 2016 could be attributed. The prevalence of
      overweight in adults in India increased from 9.0% (8.7-9.3) in 1990 to 20.4%
      (19.9-20.8) in 2016; this prevalence increased in every state of the country. For
      every 100 overweight adults aged 20 years or older in India, there were 38 adults
      (34-42) with diabetes, compared with the global average of 19 adults (17-21) in
      2016. INTERPRETATION: The increase in health loss from diabetes since 1990 in
      India is the highest among major non-communicable diseases. With this increase
      observed in every state of the country, and the relative rate of increase highest
      in several less developed low ETL states, policy action that takes these state
      level differences into account is needed urgently to control this potentially
      explosive public health situation. FUNDING: Bill & Melinda Gates Foundation; and
      Indian Council of Medical Research, Department of Health Research, Ministry of
      Health and Family Welfare, Government of India.

PMID- 30219316
TI  - The burden of chronic respiratory diseases and their heterogeneity across the
      states of India: the Global Burden of Disease Study 1990-2016.
AB  - BACKGROUND: India has 18% of the global population and an increasing burden of
      chronic respiratory diseases. However, a systematic understanding of the
      distribution of chronic respiratory diseases and their trends over time is not
      readily available for all of the states of India. Our aim was to report the
      trends in the burden of chronic respiratory diseases and the heterogeneity in
      their distribution in all states of India between 1990 and 2016. METHODS: Using
      all accessible data from multiple sources, we estimated the prevalence of major
      chronic respiratory diseases and the deaths and disability-adjusted life-years
      (DALYs) caused by them for every state of India from 1990 to 2016 as part of the
      Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016. We
      assessed heterogeneity in the burden of chronic obstructive pulmonary disease
      (COPD) and asthma across the states of India. The states were categorised into
      four groups based on their epidemiological transition level (ETL). ETL was
      defined as the ratio of DALYs from communicable diseases to those from non
      communicable diseases and injuries combined, with a low ratio denoting high ETL
      and vice versa. We also assessed the contribution of risk factors to DALYs due to
      COPD. We compared the burden of chronic respiratory diseases in India against the
      global average in GBD 2016. We calculated 95% uncertainty intervals (UIs) for the
      point estimates. FINDINGS: The contribution of chronic respiratory diseases to
      the total DALYs in India increased from 4.5% (95% UI 4.0-4.9) in 1990 to 6.4%
      (5.8-7.0) in 2016. Of the total global DALYs due to chronic respiratory diseases
      in 2016, 32.0% occurred in India. COPD and asthma were responsible for 75.6% and
      20.0% of the chronic respiratory disease DALYs, respectively, in India in 2016.
      The number of cases of COPD in India increased from 28.1 million (27.0-29.2) in
      1990 to 55.3 million (53.1-57.6) in 2016, an increase in prevalence from 3.3%
      (3.1-3.4) to 4.2% (4.0-4.4). The age-standardised COPD prevalence and DALY rates
      in 2016 were highest in the less developed low ETL state group. There were 37.9
      million (35.7-40.2) cases of asthma in India in 2016, with similar prevalence in
      the four ETL state groups, but the highest DALY rate was in the low ETL state
      group. The highest DALY rates for both COPD and asthma in 2016 were in the low
      ETL states of Rajasthan and Uttar Pradesh. The DALYs per case of COPD and asthma
      were 1.7 and 2.4 times higher in India than the global average in 2016,
      respectively; most states had higher rates compared with other locations
      worldwide at similar levels of Socio-demographic Index. Of the DALYs due to COPD
      in India in 2016, 53.7% (43.1-65.0) were attributable to air pollution, 25.4%
      (19.5-31.7) to tobacco use, and 16.5% (14.1-19.2) to occupational risks, making
      these the leading risk factors for COPD. INTERPRETATION: India has a
      disproportionately high burden of chronic respiratory diseases. The increasing
      contribution of these diseases to the overall disease burden across India and the
      high rate of health loss from them, especially in the less developed low ETL
      states, highlights the need for focused policy interventions to address this
      significant cause of disease burden in India. FUNDING: Bill & Melinda Gates
      Foundation; and Indian Council of Medical Research, Department of Health
      Research, Ministry of Health and Family Welfare, Government of India.

PMID- 30219318
TI  - Comparison of early and recent influenza A(H1N1)pdm09 isolates harboring or not
      the H275Y neuraminidase mutation, in vitro and in animal models.
AB  - After 6 years of circulation in humans, a novel antigenic variant of influenza
      A(H1N1)pdm09 (i.e., A/Michigan/45/2015) emerged in 2015-16 and has predominated
      thereafter worldwide. Herein, we compared in vitro and in vivo properties of 2016
      wild-type (WT) A/Michigan/45/15-like isolate and its H275Y neuraminidase (NA)
      variant to the original A/California/07/09-like counterparts. The H275Y mutation
      induced comparable levels of resistance to oseltamivir and peramivir without
      altering zanamivir susceptibility in both 2009 and 2016 isolates. In vitro, the
      two WT isolates had comparable replicative properties. The 2016-H275Y isolate had
      lower titers at 36 h post-inoculation (PI) (P < 0.05) while the 2009-H275Y titers
      were lower at both 24 h (P < 0.01) and 36 h PI (P < 0.001) vs the respective WTs.
      In mice, the 2016-WT isolate caused less weight losses (P < 0.001) and lower lung
      viral titers (LVTs) (P < 0.01) vs the 2009-WT. The LVTs of 2016-WT and 2016-H275Y
      groups were comparable whereas the 2009-H275Y LVTs were lower vs the respective
      WT (P < 0.01). Ferrets infected with the 2016-WT isolate and their contacts had
      higher nasal viral titers (NVTs) at early time points vs the 2009-WT group (P <
      0.01). Also, NVTs of 2016-H275Y animals were lower vs the 2016-WT group at early
      time points in both infected (P < 0.01) and contact animals (P < 0.001). In
      conclusion, while the H275Y mutation similarly impacts the A/California/07/2009-
      and A/Michigan/45/2015-like A(H1N1)pdm09 NAs, the fitness of these isolates
      differs according to animal models with the 2016 virus being less virulent in
      mice but slightly more virulent in ferrets, potentially reflecting a period of
      cumulative changes in surface and internal genes.

PMID- 30219319
TI  - Molecular heterozygosity and genetic exploitations of Trichoderma inter-fusants
      enhancing tolerance to fungicides and mycoparasitism against Sclerotium rolfsii
      Sacc.
AB  - Protoplast fusion is an imperative tool to develop Trichoderma inter-fusants
      having desire traits through genetic manipulation. Study designed to develop
      diverse Trichoderma fusants for fungicide tolerance (Mancozeb, Thiram,
      Tebuconazole, and Carbendazim) and enhanced mycoparasitic activity against
      Sclerotium rolfsii sacc. The mycoparasitic T. virens NBAII Tvs12 and fungicide
      tolerant T. koningii MTCC 796 were utilized for protoplast fusion. The derived
      inter-fusants were subjected to diploidization using d-camphor in minimal media
      followed by successive three sub culturing onto potato dextrose agar to obtain 36
      stable fusants. The stable fusants were employed for conidial size, fungicide
      tolerance, mycoparasitism, gene specific SSR amplification and molecular
      heterozygosity analysis. The results explained that 22 homozygous mutants
      illustrated characteristic of either one parental strain and 14 heterozygous
      recombinants depicted traits of both parental strains. The antagonistic activity
      of fusants against S. rolfsii depicted highest growth inhibition (87.91%) by
      potent inter-fusant (Fu 21) with improved fungicide tolerance capacity. The
      molecular study revealed highest observed heterozygocity (0.544), coefficient of
      gene differentiation (0.526) and gene flow (0.387) by Fu 21 indicating better
      genetic exploitation of parental strains into that fusant with good genetic
      purity. Principal coordinate analysis of fusants and parental strains exhibited
      65.07% total variation and confirmed the scattering pattern matched with UPGMA
      clustering pattern. The stable heterozygous Fu 21 derived from inter-fusion
      between Tvs 12 and MTCC 796 might be useful to practice eco-friendly
      bioformulation tolerance to fungicides for effective integrated stem rot disease
      management in groundnut.

PMID- 30219321
TI  - Global spatiotemporal transmission dynamics of measles virus clade D genotypes in
      the context of the measles elimination goal 2020 in India.
AB  - Measles viruses (MeV) circulating in India mainly belong to genoypes D4 and D8 of
      clade D. In the context of measles elimination goal 2020 in India, molecular
      clock and phylogeography studies would help to identify the timescales of
      evolution and track the transmission pathways of MeV. We used nucleoprotein gene
      sequences (n = 756) from GenBank, representing 86 countries (1973-2016), to study
      the spatiotemporal transmission dynamics of clade D. Genotype D4 was introduced
      into India around 1991 and genotype D8 around 1994. Recent transmissions of the
      D4 genotype of measles virus (MeV) were noted from India to the United States of
      America and East Asia region while D8 genotype importations from North America
      were noted in recent years.

PMID- 30219317
TI  - The changing patterns of cardiovascular diseases and their risk factors in the
      states of India: the Global Burden of Disease Study 1990-2016.
AB  - BACKGROUND: The burden of cardiovascular diseases is increasing in India, but a
      systematic understanding of its distribution and time trends across all the
      states is not readily available. In this report, we present a detailed analysis
      of how the patterns of cardiovascular diseases and major risk factors have
      changed across the states of India between 1990 and 2016. METHODS: We analysed
      the prevalence and disability-adjusted life-years (DALYs) due to cardiovascular
      diseases and the major component causes in the states of India from 1990 to 2016,
      using all accessible data sources as part of the Global Burden of Diseases,
      Injuries, and Risk Factors Study 2016. We placed states into four groups based on
      epidemiological transition level (ETL), defined using the ratio of DALYs from
      communicable diseases to those from non-communicable diseases and injuries
      combined, with a low ratio denoting high ETL and vice versa. We assessed
      heterogeneity in the burden of major cardiovascular diseases across the states of
      India, and the contribution of risk factors to cardiovascular diseases. We
      calculated 95% uncertainty intervals (UIs) for the point estimates. FINDINGS:
      Overall, cardiovascular diseases contributed 28.1% (95% UI 26.5-29.1) of the
      total deaths and 14.1% (12.9-15.3) of the total DALYs in India in 2016, compared
      with 15.2% (13.7-16.2) and 6.9% (6.3-7.4), respectively, in 1990. In 2016, there
      was a nine times difference between states in the DALY rate for ischaemic heart
      disease, a six times difference for stroke, and a four times difference for
      rheumatic heart disease. 23.8 million (95% UI 22.6-25.0) prevalent cases of
      ischaemic heart disease were estimated in India in 2016, and 6.5 million (6.3
      6.8) prevalent cases of stroke, a 2.3 times increase in both disorders from 1990.
      The age-standardised prevalence of both ischaemic heart disease and stroke
      increased in all ETL state groups between 1990 and 2016, whereas that of
      rheumatic heart disease decreased; the increase for ischaemic heart disease was
      highest in the low ETL state group. 53.4% (95% UI 52.6-54.6) of crude deaths due
      to cardiovascular diseases in India in 2016 were among people younger than 70
      years, with a higher proportion in the low ETL state group. The leading
      overlapping risk factors for cardiovascular diseases in 2016 included dietary
      risks (56.4% [95% CI 48.5-63.9] of cardiovascular disease DALYs), high systolic
      blood pressure (54.6% [49.0-59.8]), air pollution (31.1% [29.0-33.4]), high total
      cholesterol (29.4% [24.3-34.8]), tobacco use (18.9% [16.6-21.3]), high fasting
      plasma glucose (16.7% [11.4-23.5]), and high body-mass index (14.7% [8.3-22.0]).
      The prevalence of high systolic blood pressure, high total cholesterol, and high
      fasting plasma glucose increased generally across all ETL state groups from 1990
      to 2016, but this increase was variable across the states; the prevalence of
      smoking decreased during this period in all ETL state groups. INTERPRETATION: The
      burden from the leading cardiovascular diseases in India-ischaemic heart disease
      and stroke-varies widely between the states. Their increasing prevalence and that
      of several major risk factors in every part of India, especially the highest
      increase in the prevalence of ischaemic heart disease in the less developed low
      ETL states, indicates the need for urgent policy and health system response
      appropriate for the situation in each state. FUNDING: Bill & Melinda Gates
      Foundation; and Indian Council of Medical Research, Department of Health
      Research, Ministry of Health and Family Welfare, Government of India.

PMID- 30219320
TI  - Genome-scale analysis of evolutionary rate and selection in a fast-expanding
      Spanish cluster of HIV-1 subtype F1.
AB  - This work is aimed at assessing the presence of positive selection and/or shifts
      of the evolutionary rate in a fast-expanding HIV-1 subtype F1 transmission
      cluster affecting men who have sex with men in Spain. We applied Bayesian
      coalescent phylogenetics and selection analyses to 23 full-coding region
      sequences from patients belonging to that cluster, along with other 19 F1
      epidemiologically-unrelated sequences. A shift in the overall evolutionary rate
      of the virus, explained by positively selected sites in the cluster, was
      detected. We also found one substitution in Nef (H89F) that was specific to the
      cluster and experienced positive selection. These results suggest that fast
      transmission could have been facilitated by some inherent genetic properties of
      this HIV-1 variant.

PMID- 30219322
TI  - Septal Collateralization to Right Coronary Artery in Alcohol Septal Ablation:
      Solution to a Dangerous Pitfall.

PMID- 30219323
TI  - Chronic Total Occlusion Intervention: The Case for More Evidence.

PMID- 30219325
TI  - Double Anomalous Aortic Origin of a Coronary Artery With Intramural Course.

PMID- 30219324
TI  - Impact of Direct Transcatheter Aortic Valve Replacement Without Balloon Aortic
      Valvuloplasty on Procedural and Clinical Outcomes: Insights From the FRANCE TAVI
      Registry.
AB  - OBJECTIVES: This study sought to describe the current practices and compare
      outcomes according to the use of balloon aortic valvuloplasty (BAV) or not during
      transcatheter aortic valve replacement (TAVR). BACKGROUND: Since its development,
      aortic valve pre-dilatation has been an essential step of TAVR procedures.
      However, the feasibility of TAVR without systematic BAV has been described.
      METHODS: TAVR performed in 48 centers across France between January 2013 and
      December 2015 were prospectively included in the FRANCE TAVI (Registry of Aortic
      Valve Bioprostheses Established by Catheter) registry. We compared outcomes
      according to BAV during the TAVR procedure. RESULTS: A total of 5,784 patients
      have been included in our analysis, corresponding to 2,579 (44.6%) with BAV
      avoidance and 3,205 (55.4%) patients with BAV performed. We observed a
      progressive decline in the use of BAV over time (78% of procedures in 2013 and
      49% in the last trimester of 2015). Avoidance of BAV was associated with similar
      device implantation success (97.3% vs. 97.6%; p = 0.40). TAVR procedures without
      BAV were quicker (fluoroscopy 17.2 +/- 9.1 vs. 18.5 +/- 8.8 min; p < 0.01) and
      used lower amounts of contrast (131.5 +/- 61.6 vs. 141.6 +/- 61.5; p < 0.01) and
      radiation (608.9 +/- 576.3 vs. 667.0 +/- 631.3; p < 0.01). The rates of moderate
      to severe aortic regurgitation were lower with avoidance of BAV (8.3% vs. 12.2%;
      p < 0.01) and tamponade rates (1.5% vs. 2.3%; p = 0.04). CONCLUSIONS: We
      confirmed that TAVR without BAV is frequently performed in France with good
      procedural results. This procedure is associated with procedural simplification
      and lower rates of residual aortic regurgitation.

PMID- 30219326
TI  - Edwards SAPIEN Transcatheter Pulmonary Valve Implantation: Results From a French
      Registry.
AB  - OBJECTIVES: The aim of this study was to describe and analyze data from patients
      treated in France with the Edwards SAPIEN transcatheter heart valve (Edwards
      Lifesciences LLC, Irvine, California) in the pulmonary position. BACKGROUND: The
      Edwards SAPIEN valve has recently been introduced for percutaneous pulmonary
      valve implantation (PPVI). METHODS: From April 2011 to May 2017, 71 patients
      undergoing PPVI were consecutively included. RESULTS: The median age at PPVI was
      26.8 years (range 12.8 to 70.1 years). Primary underlying diagnoses were
      conotruncal malformations (common arterial trunk, tetralogy of Fallot and
      variants; n = 45), Ross procedure (n = 18), and other diagnoses (n = 8). PPVI
      indication was pure stenosis in 33.8% of patients, pure regurgitation in 28.1%,
      and mixed lesions in 38.1%. PPVI was successfully implemented in 68 patients
      (95.8%). Pre-stenting of the right ventricular outflow tract was performed in 70
      patients (98.6%). Early major complications occurred in 4 subjects (5.6%),
      including 1 death, 1 coronary compression, and 2 pulmonary valve embolizations.
      Three of the 4 major complications occurred in the first 15 operated patients. No
      significant regurgitation was recorded after the procedure. Transpulmonary
      gradient was significantly reduced from 34.5 to 10.5 mm Hg (p < 0.0001). No
      patient died during a 1-month follow-up period. At 1-year follow-up, the death
      rate was 2.9%, and 3 patients had undergone surgical reintervention (44%).
      CONCLUSIONS: Early results with the Edwards SAPIEN valve in the pulmonary
      position demonstrate an ongoing high rate of procedural success.

PMID- 30219327
TI  - A Randomized Trial to Assess Regional Left Ventricular Function After Stent
      Implantation in Chronic Total Occlusion: The REVASC Trial.
AB  - OBJECTIVES: The aim of this study was to investigate whether percutaneous
      coronary intervention (PCI) of chronic total occlusions (CTOs) improves left
      ventricular function. BACKGROUND: The benefit of PCI in CTOs is still
      controversial. METHODS: Patients with CTOs who were candidates for PCI were
      eligible for the study and were randomized to PCI or no PCI of CTO. Relevant
      coexisting non-CTO lesions were treated as indicated. Patients underwent cardiac
      magnetic resonance imaging at baseline and at 6 months. The primary endpoint was
      the change in segmental wall thickening (SWT) in the CTO territory. Secondary
      endpoints were improvement of regional wall motion and changes in left
      ventricular volumes and ejection fraction. Furthermore, major adverse coronary
      events after 12 months were assessed. RESULTS: The CTO PCI group comprised 101
      patients and the no CTO PCI group 104 patients. The change in SWT did not differ
      between the CTO PCI (4.1% [interquartile range: 14.6 to 19.3]) and no CTO PCI
      (6.0% [interquartile range: 8.6 to 6.0]) groups (p = 0.57). Similar results were
      obtained for other indexes of regional and global left ventricular function.
      Subgroup analysis revealed that only in patients without major non-CTO lesions
      (basal SYNTAX [Synergy Between Percutaneous Coronary Intervention With Taxus and
      Cardiac Surgery] score <=13) CTO PCI was associated with larger improvement in
      SWT than no CTO PCI (p for interaction = 0.002). Driven by repeat intervention,
      major adverse coronary event rates at 12 months were significantly lower in the
      CTO PCI group (16.3% vs. 5.9%; p = 0.02). CONCLUSIONS: No benefit was seen for
      CTO PCI in terms of the primary endpoint, SWT, or other indexes of left
      ventricular function. CTO PCI resulted in clinical benefit over no CTO PCI, as
      evidenced by reduced major adverse coronary event rates at 12 months.

PMID- 30219328
TI  - The Edwards SAPIEN Valve in the Pulmonic Position: The Not-So-New Kid on the
      Block.

PMID- 30219329
TI  - Balloon Valvuloplasty Before Transcatheter Aortic Valve Replacement: Is It Now
      Optional?

PMID- 30219330
TI  - Offline: The new politics of health in India.

PMID- 30219331
TI  - Informing NCD control efforts in India on the eve of Ayushman Bharat.

PMID- 30219333
TI  - Can hair steroids predict pregnancy longevity?
AB  - Maintaining pregnancy to term is important as preterm delivery is a risk factor
      for impaired infant development, which may have negative long-term consequences.
      Therefore, developing biomarkers that can predict pregnancy longevity during
      early gestation is essential for the prevention of preterm birth. Here we
      explored whether maternal hair testosterone and cortisol, representing the pre
      conception and first trimester periods respectively, may be used to predict
      pregnancy longevity. We recruited 125 pregnant women that contributed hair
      samples and answered a personal information questionnaire that included pre
      conception smoking. We quantified steroids using commercial enzyme-linked
      immunosorbent assay kits. Gestational age at delivery was obtained from medical
      records. We used General Linear Models to predict gestation length. The model
      that included first trimester cortisol, pre-conception smoking, pre-conception
      testosterone and the interaction between first trimester cortisol and pre
      conception smoking predicted 13% of the variance in gestation length (R2 = 0.130;
      n = 105; p =  0.007). First trimester cortisol was the best predictor of
      gestational length. Women with high levels of cortisol in their first trimester
      had an increased probability of a full-term delivery. The effect of cortisol was
      especially pronounced in smokers (beta = 1.69), compared to non-smokers (beta =
      0.45). Pre-conception testosterone also contributed to the model. Our study
      suggests that hair steroids may be used to predict pregnancy longevity, together
      with other contributing factors.

PMID- 30219335
TI  - Protein depletion with bacterial cellulose nanofibers.
AB  - In this study, we have reported a novel fabrication technique for human serum
      albumin (HSA) imprinted composite bacterial cellulose nanofibers (MIP-cBCNFs)
      used for the depletion of HSA selectively from artificial blood plasma for
      proteomic applications. Molecular imprinting was achieved by using metal ion
      coordination interactions of N-methacryloyl-(l)-histidinemethylester (MAH)
      monomer and Cu(II) ions. MAH-Cu(II)-HSA complex was polymerized with bacterial
      cellulose nanofibers (BCNFs) under constant stirring at room temperature. The
      characterization of the MIP-cBCNFs was carried out by FTIR-ATR, SEM, contact
      angle measurements and surface area measurements. The adsorption experiments of
      HSA onto the MIP-BCNFs and NIP-BCNFs from aqueous HSA solutions were investigated
      in a batch system. The selectivity of the MIP-cBCNFs was investigated by using
      non-template human transferrin (HTR), and myoglobin (Myo). The relative
      selectivity coefficients of the MIP-cBCNFs were calculated as 4.73 and 3.02 for
      HSA/HTR and HSA/Myo molecules, respectively. In addition, the depletion of HSA
      from artificial human plasma was confirmed by SDS-PAGE and 2-D gel
      electrophoresis. As a result, it has been shown that metal ion coordination
      interactions contribute to specific binding of template when preparing MIP-cBCNFs
      for the depletion of HSA with a high adsorption capacity, significant selectivity
      and reusability.

PMID- 30219334
TI  - Angiogenic lncRNAs: A potential therapeutic target for ischaemic heart disease.
AB  - Long noncoding RNAs (LncRNAs) are involved in biological processes and the
      pathology of diseases and represent an important biomarker or therapeutic target
      for disease. Emerging evidence has suggested that lncRNAs modulate angiogenesis
      by regulating the angiogenic cell process-including vascular endothelial cells
      (VECs); stem cells, particularly bone marrow-derived stem cells, endothelial
      progenitor cells (EPCs) and mesenchymal stem cells (MSCs); and vascular smooth
      muscle cells (VSMCs)-and participating in ischaemic heart disease (IHD).
      Therapeutic angiogenesis as an alternative therapy to promote coronary collateral
      circulation has been demonstrated to significantly improve the prognosis and
      quality of life of patients with IHD in past decades. Therefore, lncRNAs are
      likely to represent a novel therapeutic target for IHD through regulation of the
      angiogenesis process. This review summarizes the classification and functions of
      lncRNAs and their roles in regulating angiogenesis and in IHD, in the context of
      an overview of therapeutic angiogenesis in clinical trials.

PMID- 30219336
TI  - Assessment of collateral blood flow in patients with distal branch occlusion of
      the middle cerebral artery.
AB  - PURPOSE: Aim of this study was to evaluate the collateral blood flow between more
      distal branches of the middle cerebral artery (MCA) in the case of peripheral MCA
      branch occlusion on dynamic 4D angiograms. We sought to individually predict the
      finally resulting infarction volume with regard to the extent of collateral blood
      flow. METHODS: Overall, 35 acute ischemic stroke patients with peripheral MCA
      branch occlusion were included. Volumes of the ischemic infarctions and perfusion
      deficits were measured on diffusion-weighted images DWI and time-to-peak TTP (> 4
      s). Collateral flow on 4D MR angiograms were classified as previously specified.
      RESULTS: On DWI, the ischemic lesions had a mean volume of 3.4 +/- 15.1 mL while
      the mean volume on TTP (> 4 s) was significantly larger 22.0 +/- 18.1 mL (P <
      0.001). On dynamic 4D angiograms we observed grade 1 in 8 (22.9%), grade 2 in 4
      (11.4%), grade 3 in 10 (28.6%), and grade 4 in 13 (37.1%) patients. In comparison
      to patients with better collateralization (grade 3-4) patients with less
      sufficient collateralization (grade 0-2) demonstrated larger infarction volumes
      on initial (11.1 mL (IQR 2.9-35.5) vs. 2.1 mL (IQR 0.5-4.5), P = 0.03) and follow
      up DWI (15.5 mL (IQR 12.6-23.3) vs. 1.9 mL (IQR 0.5-4.5), P = 0.03) with
      prominent infarction growth (7.4 mL (IQR 2.6-10.1) vs. 0.9 mL (IQR 0.2-2.6), P =
      0.08). CONCLUSIONS: In the majority of cases with distal MCA branch occlusion a
      good collateral blood flow has been observed. Nevertheless, in approximately one
      quarter of patients an insufficient collateral blood flow has been detected that
      was associated with substantial infarction growth.

PMID- 30219337
TI  - Dural venous sinus stenting for idiopathic intracranial hypertension: An updated
      review.
AB  - BACKGROUND: Dural venous sinus stenting (DVSS) is an accepted treatment option in
      selected patients with medically refractory idiopathic intracranial hypertension
      and obstructive venous outflow physiology prior to cerebrospinal flow diversion
      (CSFD) surgery. There are no randomized controlled studies focusing on outcomes
      and complication rates for dural venous sinus stenting. PURPOSE: We present the
      largest comprehensive meta-analysis on DVSS for idiopathic intracranial
      hypertension (IIH) focusing on success rates, complications, and re-stenting
      rates to date. We also present a simplified approach to direct retrograde
      internal jugular vein (IJ) access for DVSS that allows for expedited procedures.
      MATERIALS AND METHODS: We performed a retrospective electronic PubMed query of
      all peer-reviewed articles in the last 15 years between 2003 to 2018. We included
      all patients who underwent dural venous sinus stenting for a medically refractive
      IIH and excluded articles without sufficient data on outcomes, complication rates
      and re-stenting rates. We also evaluated and compared outcomes in patients
      undergoing direct retrograde IJ access DVSS to traditional transfemoral vein
      access. RESULTS: A total of 29 papers and 410 patients who underwent DVSS met
      criteria for inclusion. DVSS was associated with high technical success [99.5%],
      low rates of repeated procedure [10%], and low major complication rates [1.5%].
      CONCLUSION: Our retrospective comprehensive review of DVSS for medically
      refractory IIH suggests that stenting in appropriately chosen patients is
      associated with low complication rates, high technical success, and low repeat
      procedure rates.

PMID- 30219332
TI  - Support for UNRWA's survival.

PMID- 30219338
TI  - Analysis of emergency Department Frequentation among patients with advanced CKD
      (chronic kidney disease): Lessons to optimise scheduled renal replacement therapy
      initiation.
AB  - : The decision to initiate renal replacement therapy (RRT) implies a wide margin
      of uncertainty. Glomerular filtration rate (GFR) tells us the magnitude of renal
      damage. Proteinuria indicates the speed of progression. However, nowadays more
      than 50% of patients are still initiating RRT hastily, and it is life
      threatening. HYPOTHESIS: By analysing Emergency Department (ED) frequentation and
      causes of a hurried initiation, we can better schedule the timing of the start of
      RRT. METHOD: Retrospective and observational study of all CKD patients in our
      outpatient clinic. ED frequentation and hospitalisation (Hos) time were reviewed
      during a 12-month period. We analysed: 1) time at risk, purpose (modality of
      RRT), previous comorbidity; 2) causes of ED frequentation and Hos; 3) type of
      initiation: "scheduled" vs. "non-scheduled", and within these "non-planned" vs.
      "potentially planned". RESULTS: Of a total of 267 patients (time at risk 63.987
      days, 70+/-13 years, 67% males, 38% diabetics), 68 (25%) patients came to
      hospital on 97 occasions: 39 only ED, 46 ED+Hos and 12 only Hos. ED frequentation
      was one patient every 4.3 days, and bed occupation was almost 3 per day. Main
      causes: 47% cardiopulmonary (1/3 heart failure), 11% vascular
      peripheral+cerebral, 11% gastrointestinal: 8/11 due to bleeding (all with
      anticoagulants/antiplatelet agents). Thirty-one (12%) patients initiated RRT: of
      these, 14 (45%) were scheduled (6 PD, 6 HD, and 2 living donor RTx), and 17 (55%)
      were not scheduled or were rushed, all with venous central catheter. Following
      the objectives of this study, the non-scheduled group were itemised into 2
      groups: 9 non-planned (initial indication of conservative management or patient's
      refusal to undergo dialysis, and diverse social circumstances not controllable by
      the nephrologist) and 8 were considered potentially planned (6 heart failure, one
      gastrointestinal bleeding and one peripheral vascular complication). This last
      group (potentially planned), when compared with the 14 patients who started
      treatment in a scheduled manner, had significant differences in that they were
      older, with more previous cardiac events, and GFR almost double that of the other
      group. All of them started treatment in the ED. CONCLUSION: This analysis
      provides us with knowledge on those patients who may benefit from an earlier
      preparation in RRT. We suggest that patients with previous cardiac events,
      especially with a risk of gastrointestinal bleeding, should start the preparation
      for RRT even with GFR rates of 20-25ml/min. In spite of the retrospective nature
      of this study, and taking into account the difficulties of carrying out clinical
      trials in this population, we propose this suggestion as complementary to the
      current recommendations for a scheduled start using this technique.

PMID- 30219339
TI  - Suicide in India: a complex public health tragedy in need of a plan.

PMID- 30219341
TI  - Effect of photodynamic therapy on surface decontamination in clinical orthodontic
      instruments.
AB  - The objective was to develop, characterize and test a box containing light
      emission diode (LED), Patent Deposit MU-BR20.2017.002297-3, which was named
      "Photodynamic Inactivation Device" (PID) and verify if it's suitable in microbial
      reduction or disinfection action of solid surfaces using PID. The equipment was
      made in a container of polypropylene with a lid of the same material and, for a
      better use of irradiation the internal part was covered with a layer of
      reflective aluminum. In addition, sixty boards of red LED 660 nm wavelength,
      containing three radiators each, for which the distribution of irradiation and
      spectral irradiance in all of the six internal faces were calculated in this
      device. That way, a low cost alternative was tested over three types of
      microorganisms present on the human microbiota: two strains Gram-positive (Gram
      +), Staphylococcus aureus and Streptococcus mutans and one strain Gram-negative
      (Gram -), Escherichia coli, inoculated in orthodontic instruments previously
      autoclaved. To assess the Photodynamic Inactivation (PDI) over these bacteria,
      instruments were contaminated by bacterial suspensions (3 * 108 CFU/mL) and
      ulterior treatment with a solution of 100 MUmol/L of MB for 20 min, and
      irradiated for another 20 min (energy density of 026 J/cm2). Microbial reduction
      was assessed by number counting of Colony Forming Units (CFU). At the end,
      microbial reduction of the surface of orthodontic metal instruments was compared
      with the positive group of each group. Results showed that PID caused a
      significant reduction (p < 0.05) of the microbial charge stuck in the orthodontic
      instruments. Thus, the photo prototype of the drawing is appropriate for
      phototherapy studies, granting it's advantageous to the low level light therapy
      as well as for the antimicrobial photodynamic therapy. The perspective is that
      PID may potentialize the dissemination of phototherapy studies for determining
      its proper use in health science. And, thus, propose a low cost and atoxic
      alternative for disinfection of biomedical appliances as non-critical
      instruments, allowing also for use in the food industry.

PMID- 30219340
TI  - Gender differentials and state variations in suicide deaths in India: the Global
      Burden of Disease Study 1990-2016.
AB  - BACKGROUND: A systematic understanding of suicide mortality trends over time at
      the subnational level for India's 1.3 billion people, 18% of the global
      population, is not readily available. Thus, we aimed to report time trends of
      suicide deaths, and the heterogeneity in its distribution between the states of
      India from 1990 to 2016. METHODS: As part of the Global Burden of Diseases,
      Injuries, and Risk Factors Study (GBD) 2016, we estimated suicide death rates
      (SDRs) for both sexes in each state of India from 1990 to 2016. We used various
      data sources for estimating cause-specific mortality in India. For suicide
      mortality in India before 2000, estimates were based largely on GBD covariates.
      For each state, we calculated the ratio of the observed SDR to the rate expected
      in geographies globally with similar GBD Socio-demographic Index in 2016 (ie, the
      observed-to-expected ratio); and assessed the age distribution of suicide deaths,
      and the men-to-women ratio of SDR over time. Finally, we assessed the probability
      for India and the states of reaching the Sustainable Development Goal (SDG)
      target of a one-third reduction in SDR from 2015 to 2030, using location-wise
      trends of the age-standardised SDR from 1990 to 2016. We calculated 95%
      uncertainty intervals (UIs) for the point estimates. FINDINGS: There were 230 314
      (95% UI 194 058-250 260) suicide deaths in India in 2016. India's contribution to
      global suicide deaths increased from 25.3% in 1990 to 36.6% in 2016 among women,
      and from 18.7% to 24.3% among men. Age-standardised SDR among women in India
      reduced by 26.7% from 20.0 (95% UI 16.5-23.5) in 1990 to 14.7 (13.1-16.2) per 100
      000 in 2016, but the age-standardised SDR among men was the same in 1990 (22.3
      [95% UI 14.4-27.4] per 100 000) and 2016 (21.2 [14.6-23.6] per 100 000). SDR in
      women was 2.1 times higher in India than the global average in 2016, and the
      observed-to-expected ratio was 2.74, ranging from 0.45 to 4.54 between the
      states. SDR in men was 1.4 times higher in India than the global average in 2016,
      with an observed-to-expected ratio of 1.31, ranging from 0.40 to 2.42 between the
      states. There was a ten-fold variation between the states in the SDR for women
      and six-fold variation for men in 2016. The men-to-women ratio of SDR for India
      was 1.34 in 2016, ranging from 0.97 to 4.11 between the states. The highest age
      specific SDRs among women in 2016 were for ages 15-29 years and 75 years or
      older, and among men for ages 75 years or older. Suicide was the leading cause of
      death in India in 2016 for those aged 15-39 years; 71.2% of the suicide deaths
      among women and 57.7% among men were in this age group. If the trends observed up
      to 2016 continue, the probability of India achieving the SDG SDR reduction target
      in 2030 is zero, and the majority of the states with 81.3% of India's population
      have less than 10% probability, three states have a probability of 10.3-15.0%,
      and six have a probability of 25.1-36.7%. INTERPRETATION: India's proportional
      contribution to global suicide deaths is high and increasing. SDR in India is
      higher than expected for its Socio-Demographic Index level, especially for women,
      with substantial variations in the magnitude and men-to-women ratio between the
      states. India must develop a suicide prevention strategy that takes into account
      these variations in order to address this major public health problem. FUNDING:
      Bill & Melinda Gates Foundation; and Indian Council of Medical Research,
      Department of Health Research, Ministry of Health and Family Welfare, Government
      of India.

PMID- 30219342
TI  - Industry Funding Is Correlated With Publication Productivity of US Academic
      Radiation Oncologists.
AB  - PURPOSE: Industry payments to physicians are financial conflicts of interest and
      may influence research findings and medical decisions. We aim to (1) characterize
      industry payments within radiation oncology; and (2) explore the potential
      correlation between receiving disclosed industry payments and academic
      productivity. MATERIALS/METHODS: CMS database was used to extract 2015 industry
      payments. For academic radiation oncologists, research productivity was
      characterized by h- and m-indices, as well as receipt of National Institutes of
      Health (NIH) funding, which is not an industry payment. Logistic regression
      models were used to determine whether publication metrics (m-index, h-index) and
      other study characteristics such as gender, PhD status, NIH institution funding
      status, were associated with the endpoints, research and general payments.
      Associations between the amount of payments (if any) and publication metrics were
      further studied using linear regression models. RESULTS: A total of 22,543
      individual payments totaling $25,532,482 to 2,995 radiation oncologists were
      included. Among the 1,189 academic radiation oncologists, 75% received less than
      $167; on the other hand, 10 (<1%) individuals received $6,425,728 (51%) of
      payments. On multiple logistic regression, research payments were significantly
      associated with the m-index, odds ratio 2.86 (95% confidence interval, 1.84-4.45,
      p-value <0.0001); as well as with the h-index, odds ratio 1.03 (95% confidence
      interval, 1.01-1.05, p-value <0.0001). The linear regression model shows that
      both m-index and h-index were significantly positively associated with the amount
      of general payments (p-values <0.0001). CONCLUSION: There is an association
      between disclosed payment from the industry and increased individual research
      productivity metrics. Further research to find the cause behind this association
      is warranted.

PMID- 30219344
TI  - Extending Radiologists and Their Groups.

PMID- 30219343
TI  - Needs Assessment Using a Structured Prioritization Schema: An Open Letter to PACS
      Vendors.
AB  - PURPOSE: The aim of this work was to prioritize in a quaternary academic
      environment necessary elements of a replacement PACS. METHODS: This quality
      improvement work was conducted at one academic medical center and was "not
      regulated" by the institutional review board. Three workgroups (10-15 members
      each) with unique resident, fellow, and attending radiologists; IT specialists;
      and departmental leaders convened in 2018 to prioritize elements for a PACS
      replacement project, including integrated IT tools. Each workgroup met two or
      three times and represented one of three missions (clinical, research, and
      education). Six elements assigned the highest priority were distilled from each
      workgroup. The resulting 18 elements were condensed into survey format and
      distributed to all department residents, fellows, and faculty members for 5-point
      Likert-type prioritization stratified by mission. Data were collected over 2
      weeks. RESULTS: The survey response rate was 37% (71 of 192; 17 of 44 residents,
      3 of 27 fellows, and 51 of 121 faculty members). Self-reported work effort was 63
      +/- 26% clinical, 14 +/- 11% education, 15 +/- 21% research, and 8 +/- 14%
      administration. Aggregate priority ratings across all domains were highest for
      "stable system with predictable behavior" (mean, 4.51), "minimizes repetitive non
      value-added work" (mean, 4.40), "interoperability" (mean, 4.12), and "near
      instantaneous load times" (mean, 4.07). Clinical-specific ratings for these
      elements were even higher (means, 4.85-4.90). The lowest aggregate scores were
      mobile device compatibility (mean, 3.03), connectivity to nonaffiliated sites
      (mean, 3.01), and integrated instant messaging (mean, 2.87). CONCLUSIONS: The
      department prioritized a stable and interoperable system that minimized non-value
      added work. In other words, participants wanted a functioning PACS. PACS vendors
      should prioritize a reliable experience over niche add-ons.

PMID- 30219345
TI  - New ACR Choosing Wisely Recommendations: Judicious Use of Multiphase Abdominal CT
      Protocols.

PMID- 30219346
TI  - Baseline Mammography: What Is It and Why Is It Important? A Cross-Sectional
      Survey of Women Undergoing Screening Mammography.
AB  - OBJECTIVES: Studies have shown that having a baseline mammogram, the first
      screening mammogram, available for comparison at the time of interpreting a
      subsequent mammogram significantly decreases the potential of a false-positive
      examination. Our aim was to evaluate knowledge of and perception about the
      significance of baseline mammograms in those women undergoing screening
      mammography. MATERIALS AND METHODS: A cross-sectional prospective survey study
      was conducted in women without a history of breast cancer presenting for their
      screening mammogram. Respondents were surveyed anonymously between March and
      April 2017. The questionnaire was developed by primary care providers and
      radiologists and pretested for readability and clarity. RESULTS: In all, 401
      women (87% white, 93% educated beyond high school) completed surveys in which 77%
      of women reported having yearly mammograms, 31% reported having a history of an
      abnormal mammogram, and 45% had not heard the term baseline mammogram. Of those
      who had heard the term, the most commonly reported source was their primary care
      provider (31%). Although 74% chose the correct definition of a baseline
      mammogram, 67% did not think that a baseline mammogram was important for
      decreasing associated cost, time, and discomfort due to the number of mammograms
      incorrectly read as abnormal. CONCLUSION: In a group of educated women who
      routinely get mammograms, almost one-half had not heard the term baseline
      mammogram. Furthermore, most women did not think baseline mammography was
      important for decreasing associated cost, time, and discomfort due to mammograms
      incorrectly read as abnormal. This study suggests that efforts to improve women's
      understanding of baseline mammograms and their importance are warranted, with
      greatest opportunity for health care providers and radiologists.

PMID- 30219347
TI  - Feasibility, Safety and Accuracy of Echocardiography-Fluoroscopy Imaging Fusion
      During Percutaneous Atrial Septal Defect Closure in Children.
AB  - BACKGROUND: Imaging fusion between echocardiography and fluoroscopy was recently
      developed. The aim of this study was to assess its feasibility and accuracy
      during pediatric cardiac catheterization. METHODS: Thirty-one patients (median
      weight, 26 kg; interquartile range [IQR], 21-37 kg) who underwent percutaneous
      atrial septal defect closure were prospectively included. The feasibility and
      accuracy of various imaging fusion modalities (live two-dimensional, live color
      two-dimensional, live three-dimensional and markers) with EchoNavigator software
      were assessed. To assess the accuracy of spatial registration of the
      echocardiogram on the fluoroscopic image, the occluder screw, an object that
      appeared on each image, was used as a reference tool, and the distance between
      the two when fused was measured. A distance was measured on the fusion screen
      between a marker positioned on the screw from the echocardiography screen and
      from the fluoroscopy screen (distance 1). Another distance was measured on the
      fusion screen between the screw visualized by three-dimensional echocardiography
      and by fluoroscopy (distance 2). The two distances were measured on four C-arm
      orientations in end-systolic and end-diastolic frames. RESULTS: Fusion and marker
      positioning were feasible in real time in all cases. On the fusion screen, median
      systolic and diastolic distance 1 were 0.5 mm (IQR, 0.3-1 mm) and 2 mm (IQR, 1.5
      2.5 mm; P < .0001), respectively. The marker positioned from the echocardiography
      screen was fixed on the fusion screen and did not follow the movement of the
      screw. Median systolic and diastolic distance 2 were 0.5 mm (IQR, 0-0.5 mm) and 2
      mm (IQR, 1.5-2.5 mm; P < .0001), respectively. CONCLUSIONS: Echocardiographic
      fluoroscopic imaging fusion is feasible, safe, and accurate in children weighting
      >20 kg. This technique offers a new method of imaging guidance in the
      catheterization laboratory for complex procedures and training.

PMID- 30219348
TI  - Atrial fibrillation independently linked with depression in community-dwelling
      older population. Results from the nationwide PolSenior project.
AB  - BACKGROUND: Depression is a frequently observed comorbid condition in patients
      with cardiovascular diseases. In contrast to coronary heart disease and heart
      failure there is a limited amount of published data concerning the increased
      prevalence of depression among patients with atrial fibrillation (AF). Therefore,
      we decided to assess the prevalence of depression in Polish community-dwelling
      older patients with a history of AF. METHODS: The data were collected as part of
      the nationwide PolSenior project (2007-2012). Out of 4979 individuals (age range
      65-104 years), data on self-reported history of AF were available for 4677
      (93.9%). Finally, 4049 participants without suspected moderate or severe dementia
      in Mini Mental State Examination test were assessed with the 15-item Geriatric
      Depression Scale (GDS), and a score of 6 points and more was regarded as
      suspected depression. RESULTS: Mean age (+/-SD) of the study population was 78.1
      (+/-8.3) years; 52% were males. The history of AF was reported by 788 (19.5%)
      subjects. In the univariate analysis a self-reported AF history was associated
      with 42% increase of suspected depression (41% vs 29%; P < 0.001). In
      multivariate logistic regression AF remained an independent predictor of
      depression (OR = 1.69; 95%CI: 1.43-2.00), stronger than heart failure, diabetes
      or coronary heart disease. CONCLUSIONS: In community-dwelling geriatric Polish
      population AF is associated with higher prevalence of depression. This
      association is independent from the demographic factors, disabilities and
      comorbidities (including history of stroke).

PMID- 30219349
TI  - Association between atherosclerosis and gastric biomarkers concerning
      Helicobacter pylori infection in a Chinese healthy population.
AB  - BACKGROUND: Studies have suggested that Helicobacter pylori (Hp) infection is
      associated with atherosclerotic process, while the relationship between
      pepsinogens, gastrin and atherosclerosis is unknown. AIM: The aim of the study
      was to observe association of Hp infection on atherosclerotic parameters and
      blood pressure, and explore the relationship between atherosclerotic parameters,
      blood pressure and gastric biomarkers in a healthy population. METHODS: 395
      subjects were chosen and received physical examinations, carotid artery
      ultrasound, peripheral atherosclerosis measurement, and testing of serum
      pepsinogen (PG) I and II, Hp antibody, and gastrin-17 (G-17) levels. Analyses
      were conducted by Student's t-test, ANOVA, Pearson correlation, multiple linear
      regression and binary logistic regression. RESULTS: In Hp-infected subjects,
      right carotid intima media thickness (R-CIMT) were higher (P = 0.027) and left
      ankle brachial index were higher in 45-64 years compared to 35-44 years group (P
      = 0.039, P = 0.016). Hp-IgG, PGI and G-17 respectively positively correlated with
      CIMT, pulse wave velocity and systolic blood pressure (P = 0.044, P = 0.013, P =
      0.021). The unadjusted OR in subjects with elevated CIMT for quartile IV of PGI
      was 3.542 (95% CI, 1.491-8.411), the adjusted OR was 2.916 (95% CI, 1.035-8.216).
      The unadjusted OR in subjects with elevated CIMT for quartile III of G-17 was
      4.351 (95% CI, 1.670-11.336) and for quartile IV was 3.108 (95% CI, 1.149-8.406),
      the adjusted OR for quartile III was 4.962 (95% CI, 1.515-16.258). CONCLUSIONS:
      Hp infection, higher levels of PGI and G-17 may contribute to atherosclerotic
      process by influencing atherosclerotic parameters and blood pressure in a healthy
      population, the influence on CIMT was most significant.

PMID- 30219350
TI  - Fast ultrasound-assisted synthesis of highly crystalline MIL-88A particles and
      their application as ethylene adsorbents.
AB  - Highly crystalline MIL-88A particles have been successfully synthesized via fast
      ultrasound-assisted processes. The influence of the sonication generator and
      synthesis time on the structure, crystallinity, morphology and surface area of
      the materials were studied in detail. Under this modified ultrasonic method, X
      ray diffraction patterns of MIL-88A particles showed highly crystalline
      structures in contrast to those reported in literature. Significant differences
      on surface areas and microporosity were appreciated under ultrasound conditions
      employed. Specific surface areas in the range between 179 and 359 m2 g-1 were
      obtained. That material synthesized under ultrasound batch conditions during 1 h
      had the highest surface area and microporous character. Different particle sizes
      and morphologies were obtained depending on the synthesis procedure. In general,
      probe sonicators led to smaller particle sizes. Moreover, a comparative study of
      the ethylene adsorption of the MIL-88A particles and several common MOFs in the
      ethylene adsorption was investigated. The results suggest that the modified
      ultrasound-assisted procedure for the synthesis of MIL-88A is effective to obtain
      highly crystalline particles, which are very efficient to adsorb ethylene
      molecules.

PMID- 30219351
TI  - Kinetic model for sonolytic degradation of non-volatile surfactants:
      Perfluoroalkyl substances.
AB  - Sonolytic degradation kinetics of non-volatile surfactant perfluorooctanoic acid
      (PFOA) and perfluorooctane sulfonic acid (PFOS) were investigated over a range of
      concentration, considering active cavity as a catalyst. The Michaelis-Menten type
      kinetic model was developed to empirically estimate the concentration of active
      cavity sites during reactions. Sonolytic degradation of PFOA and PFOS, as well as
      the formation of its inorganic constituents, fluoride, and sulfate, follows
      saturation kinetics of pseudo-first order at lower concentration (<2.34 uM) and
      zero order at higher concentration (>23.60 uM). Nitrate and hydrogen peroxide
      formations were 0.53 +/- 0.14 uM/min and 0.95 +/- 0.11 uM/min, respectively. At a
      power density of 77 W/L and frequency of 575 kHz, the empirically estimated
      maximum number of active cavity sites that could lead to the sonolytic reaction
      were 89.25 and 8.8 mM for PFOA and PFOS, respectively. This study suggests that a
      lower number of active cavity sites with higher temperature needed to degrade
      PFOS might be the reason for lower degradation rate of PFOS compared to that of
      PFOA. Diffusion of non-volatile surfactants at the cavity-water interface is
      found to be the rate-limiting step for the mineralization of perfluoroalkyl
      substances.

PMID- 30219352
TI  - Sonochemical synthesis of high-performance Pd@CuNWs/MWCNTs-CH electrocatalyst by
      galvanic replacement toward ethanol oxidation in alkaline media.
AB  - In this paper, a fast and effective method for the palladium (Pd) wire
      nanostructures synthesis with the great surface area through galvanic replacement
      reaction utilizing copper nanowires (CuNWS) as a template by the assistance of
      ultrasound under room temperature condition is proposed. A multifunctional
      catalyst with the mentioned nanostructure, Pd@CuNWs, and multi walled carbon
      nanotubes (MWCNTs) and chitosan (CH) as a binder was fabricated. To investigate
      the morphology and bulk composition of the prepared catalyst, Field Emission
      Scanning Electron Microscopy (FE-SEM), Energy Dispersive X-ray Spectroscopy
      (EDS), X-ray Powder Diffraction (XRD), and Inductively Coupled Plasma atomic
      Emission Spectroscopy (ICP-AES) were utilized. Various electrochemical techniques
      including chronoamperometry and cyclic voltammetry were employed for the
      electrocatalytic activity of ethanol electrooxidation and durability in basic
      solution. Electrochemical catalytic activity and durability evaluation results
      proved that the as-synthesized Pd@CuNWs/MWCNTs-CH has a super electrocatalytic
      activity compared to Pd/MWCNTs and Pd/C electrocatalysts for ethanol
      electrooxidation. Pd@CuNWs/MWCNTs-CH catalyst demonstrated substantially enhanced
      performance and long-term stability for ethanol electrooxidation in the basic
      solution in comparison to Pd/MWCNTs and commercial Pd/C demonstrated the
      potential in utilizing Pd@CuNWs/MWCNTs-CH as an efficient catalyst for ethanol
      oxidation. Additionally, thermodynamic and kinetic evaluations revealed that the
      Pd@CuNWs/MWCNTs-CH catalyst has lower activation energy compared to Pd/MWCNTs and
      Pd/C which leads to a lower energy barrier and an excellent charge transfer rate
      towards ethanol oxidation. Noticeably, the Pd@CuNWs/MWCNTs-CH presented excellent
      catalytic activities with high peak current density which was 9.5 times more than
      Pd/C, and more negative onset potential in comparison to Pd/C is acquired for
      ethanol electrooxidation denoting synergistic effect between CuNWs/MWCNs-CH and
      Pd. The Pd@CuNWs/MWCNTs-CH can be considered as a valid candidate among available
      electrocatalysts in direct ethanol fuel cells (DEFCs).

PMID- 30219353
TI  - Enhancing the cavitation erosion resistance of D8m-Ta5Si3 nanocrystalline
      coatings through Al alloying.
AB  - To investigate the effects of Al alloying on the erosion-corrosion resistance of
      beta-Ta5Si3, both a beta-Ta5Si3 coating and an Al-alloyed beta-Ta5(Si0.83Al0.17)3
      coating were synthesized on a 316 substrate by the double cathode glow discharge
      technique. The phase constitution, composition and microstructure of the two
      coatings were characterized using X-ray diffraction (XRD), scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). The two coatings
      were composed of nearly rounded D8m-beta-Ta5Si3 grains with an average size of ~4
      nm, and after the addition of Al, the preferred growth orientation for the beta
      Ta5Si3 coating changed from (4 0 0) to (0 0 2). The hardness, elastic modulus and
      contact damage resistance of the coatings were measured using a nanoindentation
      tester. The results showed that Al alloying improved the contact damage
      resistance of beta-Ta5Si3 with only a slight decrease in hardness. The erosion
      corrosion behavior of the two coatings was performed in a 3.5 wt% NaCl solution
      containing a 12 wt% concentration of silica sand under two phase slurry flow
      condition and in a 3.5 wt% NaCl solution under ultrasonic cavitation erosion
      conditions. This revealed that the Al alloyed beta-Ta5Si3 has a higher resistance
      to both erosion-corrosion and ultrasonic cavitation erosion as compared to the
      binary beta-Ta5Si3 coating.

PMID- 30219354
TI  - Microwave synthesized complex concentrated alloy coatings: Plausible solution to
      cavitation induced erosion-corrosion.
AB  - Surface phenomenon such as cavitation erosion-corrosion limits the working life
      and durability of the fluid machines through significantly altering the
      efficiency. Surface modification is an apparent and economical route for
      improving the sustainability of these components. Recently developed complex
      concentrated alloys (CCAs) or high entropy alloys (HEAs) possess exceptional
      properties owing to high configurational entropy. We developed CCA coatings on
      the stainless steel using a facial and effective microwave processing technique.
      The effect of Al molar fraction in AlxCoCrFeNi (x = 0.1-3) CCAs on ultrasonic
      cavitation erosion-corrosion was investigated in 3.5% NaCl solution. For
      comparison, cavitation erosion and electrochemical corrosion behavior of the pre-
      and post-tested samples was also performed. Detailed microstructure and
      mechanical characterization of the developed coatings were also preformed using
      different analytical techniques. The equimolar CCA coating showed apical
      degradation resistance under both pure erosion and erosion-corrosion conditions.
      The observed behavior is attributed to high strain hardening, optimal hardness,
      fracture toughness, and utmost stability of the passive layer. The phenomenal
      conjugation of these properties was associated with highest configurational
      entropy for equimolar composition resulting in sluggish diffusion, and severe
      lattice straining. Compared to pits, striations and cracks characterizing the
      morphology of the degraded stainless steel, the equimolar and Al0.1CoCrFeNi CCAs
      showed TTS (tearing topograph surface) as the dominant failure mode characterized
      by presence of microplastic deformation. The degradation of the Al3CoCrFeNi CCA
      occurred mainly through brittle failure mode. The difference in failure mechanism
      is related to the mechanical properties and underlying microstructure.

PMID- 30219355
TI  - Effects of high intensity ultrasound on disaggregation of a macromolecular
      procyanidin-rich fraction from Vitis vinifera L. seed extract and evaluation of
      its antioxidant activity.
AB  - The impact of high intensity ultrasound (US, 45 and 20 kHz) on a purified
      macromolecular fraction (more than 85% of polymeric procyanidins) from grape seed
      extract was investigated. Matrix-Assisted Laser Desorption/Ionisation (MALDI
      TOF), Reverse Phase High Performance Liquid Chromatography (RP-HPLC) and Fourier
      transform infrared spectroscopy (FTIR) revealed a modification in the chemical
      structure of these macromolecules treated by US and, particularly, bath US
      produced a considerable increase of up to 49, 41 and 35%, respectively, of
      catechins and oligomeric and polymeric procyanidin contents of the treated
      purified fraction. Bath US also produced an important increase in the number of
      procyanidins with higher molecular mass (up to decamers) and an overall increase
      in the mass signal intensities in most of the detected B-type procyanidin series,
      as well as an important increase of the antioxidant activity of the
      macromolecular fraction of procyanidins. These results could be ascribed to a
      certain disaggregation of procyanidins linked to other biopolymers, such as
      proteins and/or polysaccharides, indicating that US is an efficient technology to
      modify the chemical structure and hence the bioactivity of tannins.

PMID- 30219356
TI  - Immunoglobulin replacement therapy targeting the BCR in chronic lymphocytic
      leukemia.

PMID- 30219357
TI  - Prenatal aspects in spinal muscular atrophy: From early detection to early
      presymptomatic intervention.
AB  - With the recent advances in spinal muscular atrophy therapies, the complete
      scenario of standard of care and following up is changing not only in the
      clinical field with new phenotypes emerging but also with new expectations for
      patients, caregivers and health providers. The actual evidence indicates that
      early intervention and treatment is crucial for better response and prognosis.
      Knowledge of the prenatal and pre-symptomatic postnatal stages of the disease are
      becoming essential to consider the opportunities of timely diagnosis and to
      decide the earliest therapeutic intervention.

PMID- 30219358
TI  - Exploring the development of a household cholera-focused health literacy scale in
      James Town, Accra.
AB  - BACKGROUND: Foodborne diseases are significant reasons for in-patient and out
      patient morbidity in Ghana. Of the foodborne illnesses reported in the country,
      cholera incidence and outbreaks have resulted in food-related mortality since the
      disease was first reported in the 1970s. Cholera is now endemic in the country.
      This study attempts to develop and pilot a tool to measure household health
      literacy among the urban poor in James Town, a cholera endemic neighborhood.
      METHODS: A survey questionnaire was developed based on four of the World Health
      Organization's (WHO) recommendations on issues for measurement of health literacy
      in low- and middle-income countries. The instrument was administered to 401
      households in the community. We undertook reliability and validity analyses. T
      test, Kruskal Wallis test, and Mann-Whitney test were used to examine the
      association between the health literacy scores of the scale and subscales and the
      demographic characteristics of households. RESULTS: The reliability analyses
      showed that the instrument was internally consistent (Cronbach alpha=0.762). All
      the subscales were reliable except the beliefs about health and healthcare
      subscale. Based on content and construct validity analyses, 13 items were used
      for further examination of health literacy. We found that majority of households
      know about the information, education, and communication materials and 52% of
      households indicated that these materials remind them about the dangers of
      cholera. About 39% of the households decide together as a unit on steps to avoid
      getting cholera during an outbreak. Overall health literacy scores and the
      subscales were significantly associated with sex, age, marital status, and
      educational level of household head. Specifically, females, being married,
      increasing age and higher household income had a significant association with
      higher health literacy scores. CONCLUSION: Household units in James Town impacts
      individual health literacy through: family discussions; access to information,
      education, and communication materials on cholera; and intentional efforts made
      to get information on cholera risk factors.

PMID- 30219359
TI  - Mechanical performance of traditional distraction-based dual growing rod
      constructs.
AB  - BACKGROUND: Growing rod constructs are an important contribution in the treatment
      of children with early onset scoliosis even though these devices experience high
      rates of rod fracture. The mechanical performance of traditional, distraction
      based dual growing rod constructs is not well understood, and mechanical models
      for predicting device performance are limited. PURPOSE: Two mechanical models
      were developed and used to determine the mechanical performance of various
      growing rod configurations by increasing construct complexity. STUDY
      DESIGN/SETTING: Mechanical bench testing and finite element (FE) analysis.
      METHODS: Static and dynamic compression bending tests were based on an ASTM F1717
      method modified to accommodate dual growing rod constructs. Six construct
      configurations were tested, mechanical properties were recorded, and statistical
      analyses were performed to determine significant differences between groups: (1)
      no connectors (rods only), (2) side-by-side connectors, (3) side-by-side
      connectors plus 4 crosslinks, (4) (40-mm long tandem connectors, (5) 80-mm long
      tandem connectors, and (6) 80-mm long tandem connectors plus 4 crosslinks. FE
      analysis was used to predict the stress distribution within the constructs.
      RESULTS: The static results indicated greater stiffness, yield load, and peak
      load as the axial connector length increased (side-by-side to 40 mm tandem to 80
      mm tandem). The dynamic results showed similar cycles to failure for side-by-side
      and tandem connector (40 and 80 mm) construct configurations without crosslinks.
      Crosslinks shifted the location of rod fracture observed experimentally and
      significantly reduced the fatigue life of the construct. The flexibility of the
      construct decreased significantly as the axial connector length increased. FE
      predictions were highly consistent with the experimentally measured values and
      provided information on stress distribution within the rod for comparison to
      experimental fracture locations. CONCLUSIONS: This is the first study to evaluate
      mechanical performance of various configurations of pediatric growing rod
      constructs using preclinical models. The current study is consistent with a
      previous retrieval study in that rigid constructs lacking flexibility (ie, higher
      stiffness and lower displacement), such as those with 80-mm tandem connectors and
      multiple crosslinks, demonstrated decreased mechanical performance as shown
      through both experimental and computational models. Additionally, the
      experimental and computational findings suggest that surgeons should
      strategically consider the number of interconnecting components and subsequent
      stress concentrations along the posterior side of the rod. For example, changing
      the placement of crosslinks to low stress regions of the construct or not using
      crosslinks in the construct are options.

PMID- 30219360
TI  - Incidence and considerations of 90 day readmissions following posterior lumbar
      fusion.
AB  - BACKGROUND CONTEXT: Posterior lumbar fusion (PLF) is a commonly performed
      procedure. The evolution of bundled payment plans is beginning to require
      physicians to more closely consider patient outcomes up to 90 days after an
      operation. Current quality metrics and other databases often consider only 30
      postoperative days. The relatively new Healthcare Cost and Utilization Project
      Nationwide Readmissions Database (HCUP-NRD) tracks patient-linked hospital
      admissions data for up to one calendar year. PURPOSE: To identify readmission
      rates within 90 days of discharge following PLF and to put this in context of 30
      day readmission and baseline readmission rates. STUDY DESIGN: Retrospective study
      of patients in the HCUP-NRD. PATIENT SAMPLE: Any patient undergoing PLF performed
      in the first 9 months of 2013 were identified in the HCUP-NRD. OUTCOME MEASURES:
      Readmission patterns up to a full calendar year after discharge. METHODS: PLFs
      performed in the first 9 months of 2013 were identified in the HCUP-NRD. Patient
      demographics and readmissions were tracked for 90 days after discharge. To
      estimate the average admission rate in an untreated population, the average daily
      admission rate in the last quarter of the year was calculated for a subset of PLF
      patients who had their operation in the first quarter of the year. This study was
      deemed exempt by the institution's Human Investigation Committee. RESULTS: Of
      26,727 PLFs, 1,580 patients (5.91%) were readmitted within 30 days of discharge
      and 2,603 patients (9.74%) were readmitted within 90 days of discharge. Of all
      readmissions within 90 days, 54.56% occurred in the first 30 days. However, if
      only counting readmissions above the baseline admission rate of a matched
      population from the 4th quarter of the year (0.08% of population/day), 89.78% of
      90 day readmissions occurred within the first 30 days. CONCLUSIONS: The current
      study delineates readmission rates after PLF and puts this in the context of 30
      day readmission rates and baseline readmission rates for those undergoing PLF.
      These results are important for patient counseling, planning, and preparing for
      potential bundled payments in spine surgery.

PMID- 30219361
TI  - Microbial changes and aroma profile of nitrate reduced dry sausages during vacuum
      storage.
AB  - Slow fermented sausages with reduced ingoing amounts of sodium nitrate (control,
      15% and 25% reduction) were stored under vacuum up to three months. Changes in
      microbiology, chemical parameters and volatile compounds were studied. Residual
      nitrate was not affected by vacuum storage and its reduction resulted in a
      reduction of sausage redness. General microbial counts decreased during vacuum
      storage, though nitrate reduction increased the growth of total mesophilic
      bacteria and Gram positive cocci. Long storage time and 25% nitrate reduction
      affected microbial activity and sausage aroma profile. Short vacuum storage times
      and moderate nitrate reduction (15%) were related to compounds producing pleasant
      odours (3-hydroxy-2-butanone, ethyl octanoate, ethyl-3-methylbutanoate and 2,3
      pentanedione) and cheesy/buttery odour (2,3-butanedione and ethyl-2
      hydroxypropanoate). In contrast, 25% nitrate reduction increased compounds like
      heptanal (green, unpleasant odour) and those related to unpleasant odours,
      methanethiol (rotten odour) and methional (cooked potato).

PMID- 30219362
TI  - Changes in myofibrillar protein gel quality of porcine longissimus muscle induced
      by its stuctural modification under different thawing methods.
AB  - The effects of thawing methods (refrigeration thawing (RT, 4  degrees C), water
      immersion thawing (WT, 18  degrees C), vacuum thawing (VT, 25  degrees C),
      ultrasonic thawing (UT, 20  degrees C) and microwave thawing (MT)) on the
      conformation and gel qualities of myofibrillar protein (MP) obtained from porcine
      longissimus muscle were investigated. The results showed that MP conformation and
      gel qualities of porcine longissimus muscles by VT and UT were insignificantly
      changed compared to fresh meat (FM). A significant decrease in free amino groups
      of MP from MT illustrated that MT induced protein aggregation and oxidation (P <
      0.05). The results of circular dichroism (CD) spectra analysis and fluorescence
      spectroscopy indirectly proved that thawing can cause protein cross-linking and
      degradation, secondary structure destruction, non-hydrophilic domain exposed and
      conformational change of samples. The largest changes in solubility, surface
      hydrophobicity and particle size were obtained with MT. The effects on the
      conformation and gel quality of MP were verified during thawing process.

PMID- 30219363
TI  - Differences between porcine longissimus thoracis and semitendinosus intramuscular
      fat content and the regulation of their preadipocytes during adipogenic
      differentiation.
AB  - Intramuscular fat (IMF) plays an important role in pork quality. However,
      differences in the adipogenic regulation of IMF content between pig longissimus
      thoracis (LT) and semitendinosus (ST) remain unclear. Here, we found that IMF
      content of 180-day-old pig LT was greater than that of pig ST. Furthermore, lipid
      accumulation was earlier and greater in LT intramuscular preadipocytes (L-IMA)
      than in ST intramuscular preadipocytes (S-IMA) during differentiation.
      Interestingly, glucose consumption was lower in L-IMA than in S-IMA. Moreover,
      monounsaturated fatty acid content was greater in L-IMA than in S-IMA, whereas
      polyunsaturated fatty acid content was lower. Levels of the expression of key
      adipogenic genes were higher in L-IMA than S-IMA. Compared with S-IMA, adipogenic
      signals were more activated in L-IMA after adipogenic induction. In conclusion,
      IMF deposition differences between pig LT and ST were due to different glucose
      consumption, fatty acid composition, expression of key adipogenic genes and level
      of activating adipogenic signals between S-IMA and L-IMA during adipogenesis.

PMID- 30219364
TI  - Suggestion for a subdivision of processed meat products on the Danish market
      based on their content of carcinogenic compounds.
AB  - Carcinogenic effects in humans are ascribed to processed meat by organisations
      such as International Agency for Research on Cancer, World Cancer Research Fund
      and American Institute for Cancer Research. However, the term 'processed meat'
      covers a heterogenic group of products whose content of potential hazards differ
      considerably. To improve estimates of associations between processed meat intake
      and cancer risk we investigated ways to divide processed meat into subgroups that
      more precisely reflects its carcinogenic characteristics. We collected ingredient
      lists and declarations of salt content for >1000 processed meat products on the
      Danish market and combined the information with knowledge related to processing
      parameters. Some compounds that could affect the products' carcinogenic
      characteristics, alone or in combination, were evaluated and compared for 12
      types of processed meat products, and we suggest subgrouping of processed meat
      with similar level of carcinogenic potential, which could improve the
      understanding of the cancer risk associated with processed meat intake in
      scientific human studies.

PMID- 30219365
TI  - Rapid quantification of vesicular stomatitis virus in Vero cells using Laser
      Force Cytology.
AB  - The ability to rapidly and accurately determine viral infectivity can help
      improve the speed of vaccine product development and manufacturing. Current
      methods to determine infectious viral titers, such as the end-point dilution (50%
      tissue culture infective dose, TCID50) and plaque assays are slow, labor
      intensive, and often subjective. In order to accelerate virus quantification,
      Laser Force Cytology (LFC) was used to monitor vesicular stomatitis virus (VSV)
      infection in Vero (African green monkey kidney) cells. LFC uses a combination of
      optical and fluidic forces to interrogate single cells without the use of labels
      or antibodies. Using a combination of variables measured by the RadianceTM LFC
      instrument (LumaCyte), an infection metric was developed that correlates well
      with the viral titer as measured by TCID50 and shortens the timeframe from
      infection to titer determination from 3 days to 16 h (a 4.5 fold reduction). A
      correlation was also developed between in-process cellular measurements and the
      viral titer of collected supernatant, demonstrating the potential for real-time
      infectivity measurements. Overall, these results demonstrate the utility of LFC
      as a tool for rapid infectivity measurements throughout the vaccine development
      process.

PMID- 30219366
TI  - ICOSL-augmented adenoviral-based vaccination induces a bipolar Th17/Th1 T cell
      response against unglycosylated MUC1 antigen.
AB  - Cellular immunity established via immunotherapy holds the potential to eliminate
      solid tumors. Yet, cancer vaccines have failed to induce tumor-reactive T cells
      of sufficient quality to control disease. The inducible T cell costimulator
      (ICOS) pathway has been implicated in both the selective induction of immunity
      over tolerance as well as licensing of IL-17-polarized cellular immunity. Herein,
      we evaluated the ability of ICOS ligand (ICOSL) to augment the immunogenicity of
      adenoviral-based vaccination targeting the unglycosylated MUC1 peptide antigen.
      Vaccination disrupted immunotolerance in a transgenic mouse model recognizing
      human MUC1 as a self-antigen, inducing robust MUC1-specific immunity. Augmenting
      vaccination with ICOSL induced a bipolar Th17/Th1 effector profile, marked by
      increased MUC1-specific IL-17A production and RORgammat expression in CD4+ but
      not CD8+ T cells which predominantly expressed IFNgamma/IL-2 and T-bet. The
      polarization and maintenance of Th17 cells established following ICOSL augmented
      vaccination was highly durable, with elevated IL-17A and RORgammat levels
      detected in CD4+ T cells up to 10 months after initial immunization. Furthermore,
      provision of ICOSL significantly enhanced MUC1-specific IgG antibody in response
      to immunization. ICOSL signaling dramatically influenced CD4+ T cell phenotype,
      altering gene expression of transcription factors and regulators of effector
      function following immunization. Interestingly, ICOSL augmentation failed to
      alter the transcriptional profile of CD8+ T cells following immunization,
      affecting the magnitude, but not distribution, of gene expression. Collectively,
      ICOSL supports the induction of durable, antigen-specific Th17/Th1-mediated
      immunity in vivo, establishing a vaccination platform to enhance CD4+ T cell
      mediated antitumor immunity and providing a crucial component of an effective
      cancer vaccine.

PMID- 30219367
TI  - Reactogenicity and immunogenicity of tetanus toxoid, reduced diphtheria toxoid,
      and acellular pertussis vaccine (Tdap) in pregnant and nonpregnant women.
AB  - OBJECTIVE: Tetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss
      (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt.
      Data on reactogenicity and immunogenicity, particularly after repeated Tdap, are
      limited. We compared local injection-site and systemic reactions and serologic
      response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant
      women by self-reported prior Tdap receipt. STUDY DESIGN: Pregnant women
      (gestational age 20-34 weeks) and nonpregnant women receiving Tdap were enrolled
      in this observational study. Injection-site and systemic reactions were assessed
      for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin,
      pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were
      determined by standardized enzyme-linked immunosorbent assay at baseline and 28
      days post-vaccination. Reactogenicity and serologic responses were compared by
      pregnancy status, and within pregnant women by self-reported prior Tdap receipt.
      RESULTS: 374 pregnant and 225 nonpregnant women were vaccinated. Severe local or
      systemic reactions or "any" fever were uncommon (<=3% for both groups).
      Moderate/severe injection-site pain was significantly higher in pregnant (17.9%)
      versus nonpregnant (11.1%) women, but did not prompt a healthcare visit.
      Proportions of other moderate/severe or any severe reactions were not
      significantly higher in pregnant compared to nonpregnant women. Moderate/severe
      (including pain) and severe reactions were not significantly higher in pregnant
      women receiving repeat versus first-time Tdap. Antibody titers increased from
      baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant
      women; post-vaccination titers against pertussis toxin and filamentous
      hemagglutinin were significantly higher in nonpregnant versus pregnant women (p <
      0.01). CONCLUSION: Tdap was well-tolerated in pregnant and nonpregnant women.
      Pregnant women were more likely to report moderate/severe pain at the Tdap
      injection-site compared with nonpregnant women, but did not necessitate medical
      visits. Prior Tdap receipt did not increase occurrence of moderate/severe local
      or systemic reactions in pregnant women. Serologic responses to all vaccine
      antigens were robust. Clinical Trial Registration@ClinicalTrials.gov.
      NCT02209623. https://clinicaltrials.gov/ct2/show/NCT02209623.

PMID- 30219370
TI  - Reporting and evaluating influenza virus surveillance data: An argument for
      incidence by single year of age.

PMID- 30219371
TI  - Evidence-informed vaccine decision making: The introduction of Human Papilloma
      Virus (HPV) vaccination in the Netherlands.
AB  - Little is known about the role of (economic) information or evidence in the
      different stages of the decision-making process on vaccine introduction. By
      conducting a document analysis on the public decision-making process of
      introducing human Papilloma virus (HPV) vaccine into the national vaccination
      program (NVP) in the Netherlands, we aim to gain insight into which information
      plays a role during the introduction of a vaccination programme. A document
      analysis was performed on the public decision-making process regarding the
      introduction of HPV vaccine into the NVP in the Netherlands. Information used or
      asked for by various stakeholders during different stages of the policymaking
      process was identified. In total, 42 documents were found, analyzed and
      synthesized, for the period between August 2006 and September 2009. Documents
      were analyzed using directed content analysis based on eight broad categories of
      criteria used in decision-making frameworks for introducing a vaccine. Our
      analysis demonstrates that a wide variety of stakeholders is involved in the
      process. Financial or economic issues were stipulated in 64.3% of the documents
      and information on vaccine characteristics were discussed in 59.5%. Economic
      information from economic evaluations was discussed most (47.6%). Based on our
      analysis, it can be concluded that economic information, in particular
      information from economic evaluations, played an important role in the decision
      making process regarding the introduction of HPV-vaccination.

PMID- 30219369
TI  - Randomized, controlled, double-blinded field trial to assess Leishmania vaccine
      effectiveness as immunotherapy for canine leishmaniosis.
AB  - Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling
      studies for regional Leishmania elimination indicate that an effective vaccine is
      a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the
      Mediterranean basin, and therefore are an important target for public health
      interventions as well as a relevant disease model for human VL. No vaccine has
      been efficacious as an immunotherapy to prevent progression of already
      diagnostically positive individuals to symptomatic leishmaniasis. We performed a
      double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial
      testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted,
      vaccine, LeishTec(r), in owned hunting dogs infected with L. infantum. The
      primary outcome was reduction of clinical progression, with reduction of
      mortality as a secondary outcome. Vaccination as an immunotherapy reduced the
      risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs
      (RR: 1.33 95% C.I. 1.009-1.786 p-value: 0.0450). Receiving vaccine vs. placebo
      reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95%
      C.I.: 1.185-8.502 p-value = 0.0245). Vaccination of infected-healthy animals with
      an anti-Leishmania vaccine significantly reduced clinical progression and
      decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be
      a tool for Leishmania control.

PMID- 30219368
TI  - Protein deficiency reduces efficacy of oral attenuated human rotavirus vaccine in
      a human infant fecal microbiota transplanted gnotobiotic pig model.
AB  - BACKGROUND: Low efficacy of rotavirus (RV) vaccines in developing African and
      Asian countries, where malnutrition is prevalent, remains a major concern and a
      challenge for global health. METHODS: To understand the effects of protein
      malnutrition on RV vaccine efficacy, we elucidated the innate, T cell and
      cytokine immune responses to attenuated human RV (AttHRV) vaccine and virulent
      human RV (VirHRV) challenge in germ-free (GF) pigs or human infant fecal
      microbiota (HIFM) transplanted gnotobiotic (Gn) pigs fed protein-deficient or 
      sufficient bovine milk diets. We also analyzed serum levels of tryptophan (TRP),
      a predictor of malnutrition, and kynurenine (KYN). RESULTS: Protein-deficient
      pigs vaccinated with oral AttHRV vaccine had lower protection rates against
      diarrhea post-VirHRV challenge and significantly increased fecal virus shedding
      titers (HIFM transplanted but not GF pigs) compared with their protein-sufficient
      counterparts. Reduced vaccine efficacy in protein-deficient pigs coincided with
      altered serum IFN-alpha, TNF-alpha, IL-12 and IFN-gamma responses to oral AttHRV
      vaccine and the suppression of multiple innate immune parameters and HRV-specific
      IFN-gamma producing T cells post-challenge. In protein-deficient HIFM
      transplanted pigs, decreased serum KYN, but not TRP levels were observed
      throughout the experiment, suggesting an association between the altered TRP
      metabolism and immune responses. CONCLUSION: Collectively, our findings confirm
      the negative effects of protein deficiency, which were exacerbated in the HIFM
      transplanted pigs, on innate, T cell and cytokine immune responses to HRV and on
      vaccine efficacy, as well as on TRP-KYN metabolism.

PMID- 30219372
TI  - Healthcare governance, professions and populism: Is there a relationship? An
      explorative comparison of five European countries.
AB  - A new wave of support for populist parties and movements represents a serious
      threat to universal healthcare coverage in traditional liberal democracies and
      beyond. This article aims to contribute empirical material on the relationships
      between healthcare governance, professions and populism. It applies an
      explanatory cross-country comparative approach and uses mixed methods, including
      micro-level data garnered from international comparative databases and documents.
      Denmark, England, Germany, Italy and Turkey have been selected for comparison,
      reflecting different types of healthcare systems and populist movements. The
      results reveal variety in the ways populist discourses impact in healthcare.
      Abundant economic resources, network-based governance, high levels of trust in
      healthcare providers and doctors participating as insiders in the policy process
      seem to work as a bulwark against populist attacks on healthcare and professional
      expertise. On the other hand, poorly resourced NHS systems with doctors as
      outsiders in the policy process and major NPM reforms together with low to medium
      levels of trust in healthcare providers may be fertile ground for populist
      discourse to flourish. Our explanatory data provide hints of correlations, which
      may inform further studies to investigate causality. Yet the research highlights
      that healthcare governance and professions matter, and brings into view capacity
      for counteracting populist attacks on universal healthcare and professional
      knowledge.

PMID- 30219373
TI  - Posttraumatic stress, alcohol use, and alcohol use reasons in firefighters: The
      role of sleep disturbance.
AB  - BACKGROUND: Firefighters are at elevated risk for posttraumatic stress and
      alcohol use, with research indicating that individuals with posttraumatic stress
      are likely to use alcohol as a coping strategy. A behavioral mechanism of
      clinical relevance to these associations is sleep disturbance. Thus, it was
      hypothesized that higher posttraumatic stress and sleep disturbance would be
      associated with higher alcohol use and alcohol use coping reasons; and sleep
      disturbance would moderate the association between posttraumatic stress and
      alcohol use and alcohol use coping reasons. PROCEDURE: Participants included 639
      urban career firefighters (93.6% male; 77.9% White; Mage = 38.5). Covariates
      included fire department years and occupational stress. Structural equation
      models were tested. RESULTS: Posttraumatic stress severity was significantly,
      positively associated with alcohol use severity and alcohol use coping reasons.
      Similarly, sleep disturbance severity was significantly, positively associated
      with alcohol use severity and alcohol use coping reasons. After accounting for
      covariates and main effects, the interaction of PTSD severity and sleep
      disturbance was significantly associated with alcohol use severity, with the
      model accounting for 23.6% of variance, and alcohol use coping reasons, with the
      model accounting for 37.6% of variance. As predicted, the interaction of
      posttraumatic stress severity and sleep disturbance was not significantly
      associated with alcohol use enhancement, conformity, or social reasons.
      CONCLUSION: These findings indicate that posttraumatic stress severity is related
      to heightened alcohol use severity and alcohol use coping reasons, and this
      association is markedly stronger when firefighters' levels of sleep disturbance
      are heightened. Clinical and research implications are to be discussed.

PMID- 30219374
TI  - The application of convolution neural network based cell segmentation during
      cryopreservation.
AB  - For most of the cells, water permeability and plasma membrane properties play a
      vital role in the optimal protocol for successful cryopreservation. Measuring the
      water permeability of cells during subzero temperature is essential. So far,
      there is no perfect segmentation technique to be used for the image processing
      task on subzero temperature accurately. The ice formation and variable background
      during freezing posed a significant challenge for most of the conventional
      segmentation algorithms. Thus, a robust and accurate segmentation approach that
      can accurately extract cells from extracellular ice that surrounding the cell
      boundary is needed. Therefore, we propose a convolutional neural network (CNN)
      architecture similar to U-Net but differs from those conventionally used in
      computer vision to extract all the cell boundaries as they shrank in the
      engulfing ice. The images used was obtained from the cryo-stage microscope, and
      the data was validated using the Hausdorff distance, means +/- standard deviation
      for different methods of segmentation result using the CNN model. The
      experimental results prove that the typical CNN model extracts cell borders
      contour from the background in its subzero state more coherent and effective as
      compared to other traditional segmentation approaches.

PMID- 30219375
TI  - Comparison of quasi-Rayleigh waves and Rayleigh waves, and clarifying the cut-off
      frequency of quasi-Rayleigh waves.
AB  - The Partial Wave Method is unique in that it establishes a foundation on which
      various elastodynamic guided waves can be compared. In this paper, the method is
      used to compare quasi-Rayleigh waves and Rayleigh waves, and investigate the
      eccentricities of the Partial Wave Method at phase velocities equal to the
      Rayleigh wave speed. The comparison results in the definition of two types of
      quasi-Rayleigh waves and an explanation for quasi-Rayleigh wave behavior reported
      in the literature at frequencies that do not satisfy Viktorov's quasi-Rayleigh
      wave condition. These conclusions are also verified by the superposition of A0
      and S0 mode wave-structures calculated using the semi-analytical finite element
      method.

PMID- 30219376
TI  - Stem cell therapy for neurological disorders: A focus on aging.
AB  - Age-related neurological disorders continue to pose a significant societal and
      economic burden. Aging is a complex phenomenon that affects many aspects of the
      human body. Specifically, aging can have detrimental effects on the progression
      of brain diseases and endogenous stem cells. Stem cell therapies possess
      promising potential to mitigate the neurological symptoms of such diseases.
      However, aging presents a major obstacle for maximum efficacy of these
      treatments. In this review, we discuss current preclinical and clinical
      literature to highlight the interactions between aging, stem cell therapy, and
      the progression of major neurological disease states such as Parkinson's disease,
      Huntington's disease, stroke, traumatic brain injury, amyotrophic lateral
      sclerosis, multiple sclerosis, and multiple system atrophy. We raise important
      questions to guide future research and advance novel treatment options.

PMID- 30219377
TI  - Absence of seminal plasma from sperm-rich fraction decreases boar sperm quality
      characteristics during the course of liquid storage.
AB  - Seminal plasma (SP), the fluid that surrounds the sperm cells, is known to exert
      substantial influence on sperm physiology. The SP has a pivotal role in sperm
      function in vivo, and due to its components, it functions in an ambiguous manner
      in vitro, simultaneously possessing deleterious and beneficial effects. This
      experiment aimed to describe the differences between the presence or absence of
      SP from the sperm-rich fraction on some spermatozoa characteristics (kinetics,
      plasma and acrosome membrane integrity, lipid peroxidation and capacitation-like
      changes). Furthermore, this experiment focused on distinguishing the effects of
      SP on the variables evaluated from the effects of centrifugation during SP
      removal. Total and progressive sperm motility, as well as integrity of plasma and
      acrosome membranes, were less (P <  0.05) in the absence of SP. Membrane lipid
      peroxidation (P <  0.05) and sperm membrane stability (P < 0.05) did not differ
      among treatments. The SP from the sperm-rich fraction is important for the
      maintenance of adequate structural and functional characteristics of extended
      liquid boar semen and should be present in seminal doses throughout storage.
      Furthermore, the detrimental effect on the variables evaluated was caused solely
      by the absence of SP and not by the process of removal through centrifugation at
      500 x g for 10 min.

PMID- 30219378
TI  - Comparison of different brown and white layer hybrid embryonic development and
      uptake of nutrients in the egg.
AB  - The objective of this study was to evaluate the comparison of different brown and
      white layers in embryonic development and uptake of nutrients in the egg. A total
      of 360 fertilized eggs obtained from two brown (Atak-S and Brown Nick) and two
      white (Atabey and Nick) layer breeders at 28 wk old. Hatching eggs from each
      genotype were examined on the day of setting for fresh egg analysis and then at
      the beginning of the embryonic day (E19) and embryonic day (E21) for egg, embryo
      and villus analysis. Differences in egg weight, shell percentages, relative
      weight of yolk and albumen, relative weight and length of embryo, villus height,
      some values of shell, yolk and albumen and relative chick weight in examined
      hybrids were significant. Yolk sac utilization of embryos during the incubation
      in the white layer hybrids was greater than that in the brown layer hybrids.
      Villus heights in the duodenum, jejenum and ileum of embryos in the brown layer
      hybrids was greater than that in the white layer hybrids. Genotype is important
      parameter to determine the egg composition at the same age and in animals being
      fed the same diet. It was observed that the consumption of yolk and shell
      nutrients from the embryos during the incubation was not related to whether
      embryos were from the brown or white layer hybrids. Only uptake of the yolk sac
      and villus height in the embryo among examined variables varied depending on
      whether the embryos were from the brown or white layer hybrids.

PMID- 30219379
TI  - Relationships of nutritional plane and feed efficiency with sexual development
      and fertility related measures in young beef bulls.
AB  - Sexual development in beef bulls appears to be influenced by nutritional plane
      and feed efficiency. Yearling bulls fed high (GRAIN = 49) and moderate (ROUGHAGE
      = 109) nutritional planes, were submitted to a performance test where scrotal
      circumference (SC), scrotum and testis ultrasonograms and hormones were monitored
      throughout. Scrotal thermographs, blood cell counts and semen were evaluated at
      the end of the test. Residual feed intake (RFI) was the measure of feed
      efficiency, and bulls within each population were characterized as efficient and
      inefficient. During the test period, the GRAIN group had greater triiodothyronine
      (T3), leptin and scrotal skin thickness (SST) while having greater T3, leptin, %
      motile sperm, % normal sperm, scrotal temperature and values for red blood cell
      variables at the end of the test when compared to the ROUGHAGE group. During the
      test, the efficient GRAIN group had lesser testis pixel intensity while at the
      end of the performance test the bulls of this group had greater % normal sperm
      and lower testis pixel intensity compared to bulls in inefficient GRAIN group. In
      comparison, the efficient ROUGHAGE group had less T3, SC and SST while at the end
      of the test these bulls had less T3, leptin, SC, SST and scrotal temperature
      compared to bulls in the inefficient ROUGHAGE group. Complete blood cell
      variables, semen quality, scrotal biometry and thermography explained most of the
      variation in RFI. Results of the present study support the hypothesis that there
      is an antagonistic relationship between feed efficiency and sexual development in
      young bulls, which seems partially offset when there is a greater plane of
      nutrition. Thus, feed efficiency should be factored in the reproductive
      evaluation of sires.

PMID- 30219380
TI  - Effects of oligomeric proanthocyanidins on quality of boar semen during liquid
      preservation at 17  degrees C.
AB  - The use of antioxidants is an important aspect in the preservation of boar semen.
      Oligomeric proanthocyanidins (OPC) are an effective natural antioxidants that
      scavenges free radicals and reactive oxygen species (ROS). This study was
      designed to investigate the antioxidative effect of OPC on boar semen quality
      during liquid preservation at 17  degrees C. The effects of different
      concentrations of OPC on sperm quality variables, antioxidant effects and
      fertility were analyzed in this experiment. Semen collected from six Guanzhong
      Black boars and was diluted with Beltsville thawing solution (BTS). During the
      process of liquid preservation at 17  degrees C, the variables assessed were
      measured and analyzed every 24 h. The addition of OPC improved boar sperm
      motility, acrosome integrity, membrane integrity, and mitochondrial membrane
      potential as compared with that of the control group (P <  0.05). Meanwhile,
      malondialdehyde content (MDA) and ROS content was less after adding OPC, thereby
      improving the total antioxidant capacity (T-AOC) (P <  0.05). Different
      concentrations of OPC have different degrees of protective effects on boar semen
      quality. The results indicate that 50 MUg/mL of OPC was the optimum
      concentration, and that the conception rate, litter size, and survival rate
      increased at this concentration as compared with that of the control group (P < 
      0.05). In summary, the addition of OPC to BTS diluents can improve the quality of
      boar semen at 17  degrees C during liquid preservation. Further research is
      needed to understand the mechanism by which OPC provides protection to boar semen
      during preservation in vitro.

PMID- 30219381
TI  - Effect of bone marrow stromal cells in combination with biomaterials in early
      phases of distraction osteogenesis: An experimental study in a rabbit femur
      model.
AB  - Acceleration of the consolidation of the distracted bone is a relevant medical
      need. As a platform to improve in vivo bone engineering, we developed a novel
      distraction osteogenesis (DO) model in a rabbit large bone (femur) and tested if
      the application of cultured bone marrow stromal cells (BMSCs) immediately after
      the osteotomy promotes the formation of bone. This report consists of two
      components, an animal study to evaluate the quality of the regenerate following
      different treatments and an in vitro study to evaluate osteogenic potential of
      BMSC cultures. To illuminate the mechanism of action of injected cells, we tested
      stem cell cultures enriched in osteogenic-BMSCs (O-BMSCs) as compared with
      cultures enriched in non-osteogenic BMSCs (NO-BMSCs). Finally, we included a
      group of animals treated with biomaterials (fibrin and ground cortical bone) in
      addition to cells. Injection of O-BMSCs promoted the maturity of distracted
      callus and decreased fibrosis. When combined with biomaterials, O-BMSCs modified
      the ossification pattern from endochondral to intramembranous type. The use of NO
      BMSCs not only did not increase the maturity but also increased porosity of the
      bone. These preclinical results indicate that the BMSC cultures must be tested in
      vitro prior to clinical use, since a number of factors may influence their
      outcome in bone formation. We hypothesize that the use of osteogenic BMSCs and
      biomaterials could be clinically beneficial to shorten the consolidation period
      of the distraction and the total period of bone lengthening.

PMID- 30219382
TI  - Combat vascular injury: Influence of mechanism of injury on outcome.
AB  - BACKGROUND: Haemorrhage is the leading cause of death on the battlefield. Seventy
      percent of injuries are due to explosive mechanisms. Anecdotally, these patients
      have had poorer outcomes when compared to those with penetrating mechanisms of
      injury (MOI). We wished to test the hypothesis that outcomes following vascular
      reconstruction were worse in blast-injured than non blast-injured patients.
      METHODS: Retrospective cohort study. British and American combat casualties with
      arterial injuries sustained in Iraq or Afghanistan (2003-2014) were identified
      from the UK Joint Theatre Trauma Registry (JTTR). Eligibility included explosive
      or penetrating MOI, with follow-up to UK hospital discharge, or death. Outcomes
      were mortality, amputation, graft thrombosis, haemorrhage, and infection.
      Statistical analysis was performed using Pearson Chi-Square test, t-tests, ANOVA
      or non-parametric equivalent, and survival analyses. RESULTS: One hundred and
      fifteen patients were included, 80 injured by explosive and 35 by penetrating
      mechanisms. Evacuation time, ISS, number of arterial injuries, age and gender
      were comparable between groups. Seventy percent of arterial injuries resulted
      from an explosive MOI. The explosive injuries group received more blood products
      (p = 0.008) and suffered more regions injured (p < 0.0001). Early surgical
      interventions in both were ligation (n = 36, 31%), vein graft (n = 33, 29%) and
      shunting (n = 9, 8%). Mortality (n = 12, 10%) was similar between groups.
      Differences in limb salvage rates following explosive (n = 17, 53%) vs
      penetrating (n = 13, 76.47%) mechanisms approached statistical significance (p =
      0.056). Nine (28%) vein grafted patients developed complications. No evidence of
      a difference in the incidence of vein graft thrombosis was found when comparing
      explosive with non-explosive cohorts (p = 0.154). CONCLUSIONS: The recorded
      numbers of vein grafts following combat arterial trauma in are small in the JTTR.
      No statistically-significant differences in complications, including vein graft
      thrombosis, were found between cohorts injured by explosive and non-explosive
      mechanisms.

PMID- 30219383
TI  - Analysis of mycobacterial infection-induced changes to host lipid metabolism in a
      zebrafish infection model reveals a conserved role for LDLR in infection
      susceptibility.
AB  - Changes to lipid metabolism are well-characterised consequences of human
      tuberculosis infection but their functional relevance are not clearly elucidated
      in these or other host-mycobacterial systems. The zebrafish-Mycobacterium marinum
      infection model is used extensively to model many aspects of human-M.
      tuberculosis pathogenesis but has not been widely used to study the role of
      infection-induced lipid metabolism. We find mammalian mycobacterial infection
      induced alterations in host Low Density Lipoprotein metabolism are conserved in
      the zebrafish model of mycobacterial pathogenesis. Depletion of LDLR, a key lipid
      metabolism node, decreased M. marinum burden, and corrected infection-induced
      altered lipid metabolism resulting in decreased LDL and reduced the rate of
      macrophage transformation into foam cells. Our results demonstrate a conserved
      role for infection-induced alterations to host lipid metabolism, and specifically
      the LDL-LDLR axis, across host-mycobacterial species pairings.

PMID- 30219384
TI  - Effect of partial dietary replacement of fishmeal by yellow mealworm (Tenebrio
      molitor) larvae meal on the innate immune response and intestinal antioxidant
      enzymes of rainbow trout (Oncorhynchus mykiss).
AB  - The present study investigated the effects of 25 and 50% dietary inclusion of
      yellow mealworm, Tenebrio molitor (TM), larvae on the intestinal antioxidant
      enzymes, lipid peroxidation and immune system of rainbow trout, Oncorhynchus
      mykiss. Fish were fed for 90 days with a control diet (TM0) or with 2 test diets
      (TM25 and TM50) where 35 and 67% of the fishmeal was replaced by TM larvae meal
      respectively. At the end of the growth trial, humoral immune parameters were
      assessed in the sera of the fish and the activities of antioxidant enzymes were
      measured in intestine homogenates. The present results show a strong increase of
      the activity of the antioxidant intestinal enzymes and reduction of lipid
      peroxidation. Increased trypsin inhibition and faster antibacterial activity of
      the serum were also detected. These evidences could be due to the physiological
      similarities between the exoskeleton of parasites and insects. The present
      findings reinforce the previous results which revealed a positive effect of the
      dietary TM on rainbow trout growth and further confirm its adequacy for fishmeal
      partial replacement in aquafeed.

PMID- 30219385
TI  - Ark shell Scapharca broughtonii hemocyte response against Vibrio anguillarum
      challenge.
AB  - Scapharca broughtonii is one of the most important Arcidae aquaculture species in
      the Asia-Pacific region. We aimed to investigate the immune responses of
      hemocytes from ark shell S. broughtonii hemolymph against pathogens. Hemocyte
      ultrastructure and immunological activity in response to Vibrio anguillarum
      challenge were observed by scanning and transmission electron microscopy. Before
      ultrastructure observation, we used the API ZYM semi-quantitative kit to evaluate
      the levels of hydrolytic enzymes in the plasma and hemocytes following V.
      anguillarum infection. An enzyme-linked immunosorbent assay kit was used to
      investigate the variation in the lysozyme activity and hemocytes following
      bacterial infection. The results showed that hemocytes were the main defense
      cells against bacterial infection, whereas plasma played a role in the transport
      and support of hemocytes. It was presumed that an important function of lysozymes
      and hydrolytic enzymes in lysosomes was for bacterial digestion. Three major
      types of hemocytes were observed, namely, red blood cells (RBCs), white blood
      cells (WBCs), and thrombocytes (TCs). Scanning electron microscopy showed that
      the normal RBCs appeared pie-shaped with 10 MUm diameter and 4 MUm central
      thickness, whereas WBCs were spherical in shape with varying sizes, 4-8 MUm
      diameter, and included small lymphocytes. TCs were long, spindle-shaped, and 12
      20 MUm in length. The cell membrane surface was smooth and even for all cells
      before pathogen challenge. Under transmission electron microscopy, RBCs displayed
      a limited ability to devour and digest bacteria adherent to the cell surface
      following infection. Many hemoglobin particles were observed in the RBC
      cytoplasm. WBCs were very active against bacterial invasion and showed a strong
      ability to digest and decompose infected and wrapped V. anguillarum through
      phagocytosis and lysosome fusion. Digestive vacuoles rapidly became transparent
      and were thought to contain increasing quantities of pathogen-induced lysozymes.
      WBCs that devoured pathogenic bacteria were prone to deformation as well as
      adhesion to each other. TCs were rich in endoplasmic reticulum (ER) content in
      their cytoplasm and were widely connected in a net-shaped structure. Mitochondria
      in TCs formed clusters upon invasion of V. anguillarum in the hemolymph. TCs
      disintegrated to release the ER into the plasma to form a mesh that facilitated
      clotting. The ability of circulating hemocytes to quickly modify their
      morphologies and stainability suggests that S. broughtonii is endowed with highly
      dynamic hemocyte populations capable of coping with environmental changes and
      rapidly growing pathogens.

PMID- 30219386
TI  - Isolation and characterization of a Raf gene from Chinese shrimp Fenneropenaeus
      chinensis in response to white spot syndrome virus infection.
AB  - Raf is a member in the Ras/Raf/MAPKK/MAPK signaling transduction pathway. To
      obtain a better understanding of Raf in the interaction between the Chinese
      shrimp Fenneropenaeus chinensis and white spot syndrome virus (WSSV), the
      sequence of cDNA of Raf from F. chinensis (FcRaf) was obtained. The FcRaf gene
      contained a 2421 bp open reading frame (ORF). The FcRaf shared most
      characteristic of Raf protein, such as the Raf-like Ras-binding domain (RBD),
      phorbol esters/diacylglycerol binding domain (C1 domain), and catalytic domain of
      the serine/threonine kinases, Raf (STKc_Raf). The sequence of functional domains
      of Raf protein was relatively conserved. The FcRaf mRNA was detected in the
      tissues of gill, muscle, and hepatopancreas from normal F. chinensis. The mRNA
      abundance level of FcRaf in the gill was the highest, which was 2.7-fold the
      level in the hepatopancreas. The expression level of FcRaf was significantly (P <
      0.05) up-regulated in the tissues of gill, muscle, and hepatopancreas post WSSV
      infection, which suggested that FcRaf might be involved in the interaction
      between F. chinensis and WSSV. Two SNP loci were identified in the ORF, one of
      which was a C-T mis-sense mutation, where an Ala was replaced by a Val, and
      induced the predicted protein secondary structure change. Considering the
      relatively low MAF (0.07), whether this mis-sense mutation was a detrimental
      mutation needs further investigation.

PMID- 30219387
TI  - Transcriptome analysis of the critically endangered Dabry's sturgeon (Acipenser
      dabryanus) head kidney response to Aeromonas hydrophila.
AB  - Dabry's sturgeon (Acipenser dabryanus), as a living fossil, is considered a
      critically endangered aquatic animal in China. To date, the immune system of this
      species remains largely unknown, with limited available sequence information. In
      addition, increasing incidence of bacterial pathogenic diseases has been
      reported. Hence, the present study aimed to characterize comprehensively
      transcriptome profile of the head kidney from Dabry's sturgeon infected with
      Aeromonas hydrophila using Illumina platform. Over 42 million high-quality reads
      were obtained and de novo assembled into a final set of 195240 unique transcript
      fragments (unigenes), with an average length of 564 bp. Approximately 41702
      unigenes were annotated in the NR NCBI database. Dabry's sturgeon unigenes had
      the highest number of hits with 14365 (34.45%) to Lepisosteus oculatus. The
      195240 unigenes were assigned to three Gene Ontology (GO) categories: biological
      process, cellular component, and molecular function. Among them, 27770 unigenes
      were clustered into 26 Eukaryotic Orthologous Group (KOG) functional categories,
      and 36031 unigenes were mapped to 335 known Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathways. After A. hydrophila administration, 1728 differentially
      expressed unigenes were identified, including 980 upregulated and 748
      downregulated unigenes. Further KEGG enrichment analysis of these unigenes
      identified 16 immune-related pathways, including the Toll-like receptor signaling
      pathway, chemokine signaling pathway, complement and coagulation pathway, RIG-I
      like receptor signaling pathway, and NOD-like receptor signaling pathway. 20 DEGs
      were selected and their expression patterns are largely consistent with the
      transcriptome profile analysis, which clearly validated the reliability of the
      DEGs in transcriptome analysis. This work revealed novel gene expression patterns
      of Dabry's sturgeon host defense and contributes to a better understanding of the
      immune system and defense mechanisms of Dabry's sturgeon in response to bacterial
      infection. The results provide valuable references for studies in sturgeons that
      lack complete genomic sequences, and could also be helpful for the analyzing
      evolution among cartilaginous and teleost fish.

PMID- 30219388
TI  - Distinct beta-glucan molecules modulates differently the circulating cortisol
      levels and innate immune responses in matrinxa (Brycon amazonicus).
AB  - This study investigated the effects of two beta-glucan molecules with different
      purities and isolated by different biotechnological processes on the immune
      response of matrinxa (Brycon amazonicus) prior and after challenge with Aeromonas
      hydrophila. In this sense, we evaluated serum cortisol and plasma glucose levels,
      the number of leukocytes (lymphocytes, neutrophils and monocytes), as well as the
      respiratory activity of leukocytes prior to, 6 and 24 h post infection (hpi).
      During 15 days, fish were fed with diets containing 0.1% of two beta-glucans
      (beta-G 1 and beta-G 2, with 71 and 62% of purity, respectively) and then
      submitted to challenge. Results were compared with a positive control group fed
      with a beta-glucan-free diet. A negative control group, also fed with beta-glucan
      free diet but inoculated with PBS, was established to evaluate the effect of
      handling during injection. Our results showed that different beta-glucans
      affected differently the biological responses of matrinxa. The betaG 2 modulated
      the cortisol profile prior to and after the acute infection with A. hydrophila,
      and increased the mobilization and activity of leukocytes. The infection promoted
      lymphopenia at 6 hpi and both beta-glucans increased the circulating lymphocyte
      population 24 hpi. Moreover, the beta-G 2 prevented the infection-induced
      neutrophilia at 6 and 24 hpi. Finally, the beta-G 2 caused a marked increase in
      the circulating monocytes prior to infection, and a reduction at 6 hpi that was
      reversed at 24 hpi. In summary, our study demonstrates that beta-G 2 was more
      efficient on the induction of the cell-mediate immunity in matrinxa.

PMID- 30219389
TI  - IL-17A is functionally relevant and a potential therapeutic target in bullous
      pemphigoid.
AB  - IL-17A has been identified as key regulatory molecule in several autoimmune and
      chronic inflammatory diseases followed by the successful use of anti-IL-17
      therapy, e.g. in ankylosing spondylitis and psoriasis. Bullous pemphigoid (BP) is
      the most frequent autoimmune blistering disease with a high need for more
      specific, effective and safe treatment options. The aim of this study was to
      clarify the pathophysiological importance of IL-17A in BP. We found elevated
      numbers of IL-17A+ CD4+ lymphocytes in the peripheral blood of BP patients and
      identified CD3+ cells as major source of IL-17A in early BP skin lesions. IL17A
      and related genes were upregulated in BP skin and exome sequencing of 51 BP
      patients revealed mutations in twelve IL-17-related genes in 18 patients. We have
      subsequently found several lines of evidence suggesting a significant role of IL
      17A in the BP pathogenesis: (i) IL-17A activated human neutrophils in vitro, (ii)
      inhibition of dermal-epidermal separation in cryosections of human skin incubated
      with anti-BP180 IgG and subsequently with anti-IL-17A IgG-treated leukocytes,
      (iii) close correlation of serum IL-17A levels and diseases activity in a mouse
      model of BP, (iv) IL17A-deficient mice were protected against autoantibody
      induced BP, and (v) pharmacological inhibition of lL-17A reduced the induction of
      BP in mice. Our data give evidence for a pivotal role of IL-17A in the
      pathophysiology of BP and advocate IL-17A inhibition as potential novel treatment
      for this disease.

PMID- 30219390
TI  - Autophagy: A new concept in autoimmunity regulation and a novel therapeutic
      option.
AB  - Nowadays, pharmacologic treatments of autoinflammatory diseases are largely
      palliative rather than curative. Most of them result in non-specific
      immunosuppression, which can be associated with broad disruption of natural and
      induced immunity with significant and sometimes serious unwanted injuries. Among
      the novel strategies that are under development, tools that modulate the immune
      system to restore normal tolerance mechanisms are central. In these approaches,
      peptide therapeutics constitute a class of agents that display many
      physicochemical advantages. Within this class of potent drugs, the phosphopeptide
      P140 is very promising for treating patients with lupus, and likely also patients
      with other chronic inflammatory diseases. We discovered that P140 targets
      autophagy, a finely orchestrated catabolic process, involved in the regulation of
      inflammation and in the biology of immune cells. In vitro, P140 acts directly on
      a particular form of autophagy called chaperone-mediated autophagy, which seems
      to be hyperactivated in certain subsets of lymphocytes in lupus and in other
      autoinflammatory settings. In lupus, the "correcting" effect of P140 on autophagy
      results in a weaker signaling of autoreactive T cells, leading to a significant
      improvement of pathophysiological status of treated mice. These findings also
      demonstrated ex vivo in human cells, open novel avenues of therapeutic
      intervention in pathological conditions, in which specific and not general
      targeting is highly pursued in the context of the new action plans for
      personalized medicines.

PMID- 30219391
TI  - In vitro antimicrobial activity of the essential oil from Vanillosmopsis arborea
      Barker (Asteraceae) and its major constituent, alpha-bisabolol.
AB  - Vanillosmopsis arborea Barker (Asteraceae), commonly known as "candeeiro" is an
      endemic tree to the Caatinga biome, in northeast Brazil. The major component of
      its essential oil is alpha-bisabolol, a monocyclic sesquiterpene alcohol with
      several biological activities reported. In this study, the antimicrobial activity
      of the essential oil of V. arborea was investigated in comparison with its major
      component alpha-bisabol. The antimicrobial activity was performed against
      Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 12692, Candida albicans
      (CA) INCQS 40006, Candida krusei (CK) INCQS 40095, Candida tropicalis (CT) INCQS
      40042, and multiresistant bacterial strains Staphylococcus aureus 03 and
      Escherichia coli 08 by the microdilution method and direct contact modulation.
      The results showed that all strains were sensitive to the samples, except E. coli
      against the essential oil. Both the essential oil and the alpha-bisabolol had a
      synergistic effect against all strains, except for ampicillin against S. aureus
      03, which did not show any modifications when combined with the oil. These data
      show the potential of V. arborea essential oil as an antibiotic modulator as well
      as a source of bioactive compounds with potential for the development of
      antimicrobial drugs as well as adjuvant to therapy against these pathogens.

PMID- 30219392
TI  - Synthesis and evaluation of antibacterial and antibiofilm activities of pyridin-2
      yl hexanoate.
AB  - Synthesized Pyridin-2-yl hexanoate was screened for its antibacterial and
      antibiofilm activities using the broth microdilution method and XTT assay
      respectively. The obtained results revealed that synthesized molecule inhibited
      the growth of pathogenic bacteria (MICs value ranged from 80 to 640 MUg ml-1).
      Moreover, it induced a strong antibiofilm effect against Gram positive cocci
      (BIC50 was 366, 378 and 412 MUg ml-1 for Streptococcus mutans ATCC 25175,
      Streptococcus salivarius ATCC 13419 and Streptococcus oralis ATCC 6249
      respectively). Basis on these results, pyridin-2-yl hexanoate may be considered
      as effective compound with antibacterial and antibiofilm activities.

PMID- 30219393
TI  - Changing the Tide of Left Atrial Inflow: Improved Pulmonary Vein Patterns Predict
      Smooth Sailing After Percutaneous Mitral Valve Repair.

PMID- 30219394
TI  - Systolic Stretch Characterizes the Electromechanical Substrate Responsive to
      Cardiac Resynchronization Therapy.
AB  - OBJECTIVES: In this study, the authors tested the hypotheses that the systolic
      stretch index (SSI) developed by computer modeling and applied using
      echocardiographic strain imaging may characterize the electromechanical substrate
      predictive of outcome following cardiac resynchronization therapy (CRT). They
      included patients with QRS width 120 to 149 ms or non-left bundle branch block
      (LBBB), where clinical uncertainty for CRT exists. They further tested the
      hypothesis that global longitudinal strain (GLS) has additional prognostic value.
      BACKGROUND: Response to CRT is variable. Guidelines favor patient selection by
      electrocardiographic LBBB with QRS width >=150 ms. METHODS: The authors studied
      442 patients enrolled in the Adaptive CRT 94-site randomized trial with New York
      Heart Association functional class III-IV heart failure, ejection fraction <=35%,
      and QRS >=120 ms. A novel computer program semiautomatically calculated the SSI
      from strain curves as the sum of posterolateral prestretch percent before aortic
      valve opening and the septal rebound stretch percent during ejection. The primary
      endpoint was hospitalization for heart failure (HF) or death, and the secondary
      endpoint was death over 2 years after CRT. RESULTS: In all patients, high
      longitudinal SSI (>= group median of 3.1%) was significantly associated with
      freedom from the primary endpoint of HF hospitalization or death (hazard ratio
      [HR] for low SSI: 2.17; 95% confidence interval [CI]: 1.45 to 3.24, p < 0.001)
      and secondary endpoint of death (HR for low SSI: 4.06; 95% CI: 1.95 to 8.45, p <
      0.001). Among the 203 patients with QRS 120 to 149 ms or non-LBBB, those with
      high longitudinal SSI (>= group median of 2.6%) had significantly fewer HF
      hospitalizations or deaths (HR for low SSI: 2.08; 95% CI: 1.27 to 3.41, p =
      0.004) and longer survival (HR for low SSI: 5.08; 95% CI: 1.94 to 13.31, p <
      0.001), similar to patients with LBBB >=150 ms. SSI by circumferential strain had
      similar associations with clinical outcomes, and GLS was additive to SSI in
      predicting clinical events (p = 0.001). CONCLUSIONS: Systolic stretch by strain
      imaging characterized the myocardial substrate associated with favorable CRT
      response, including in the important patient subgroup with QRS width 120 to 149
      ms or non-LBBB. GLS had additive prognostic value.

PMID- 30219395
TI  - Prognostic Value of Global Longitudinal Strain in Hypertrophic Cardiomyopathy: A
      Systematic Review of Existing Literature.
AB  - OBJECTIVES: The association of left ventricular global longitudinal strain (LV
      GLS) with clinical outcomes in patients with hypertrophic cardiomyopathy (HCM)
      has been examined in multiple studies. The authors conducted a systematic review
      aimed at summarizing and critically appraising the current evidence. BACKGROUND:
      HCM is a common genetic cardiovascular disease with an estimated prevalence of 1
      in 500 patients. LV-GLS derived from speckle tracking echocardiography is a
      sensitive noninvasive method of assessing regional left ventricular function.
      Several studies have suggested association of abnormal LV-GLS with outcomes in
      HCM patients. METHODS: A computerized literature search of all English language
      publications in the PubMed and EMBASE databases was made looking at all
      randomized and nonrandomized studies conducted on patients with HCM where
      association of LV-GLS with clinical outcomes was studied. We then manually
      searched the reference lists of included articles. The Preferred Reporting Items
      for Systematic reviews and Meta-Analyses statement (PRISMA) of reporting
      systematic reviews was used. RESULTS: Our search yielded a total of 14
      observational studies published between 2009 and 2017 with a total of 3154
      patients with HCM. Eleven of the 14 studies included a composite cardiac outcome
      which included mortality as their primary outcome of interest and 3 of the 14
      studies looked at association of LV-GLS with ventricular arrhythmias and/or
      implantable cardiac defibrillator discharge. We noted wide variability in
      inclusion, methodology, follow-up, and consequently effect estimates, which was
      not conducive to performing a meta-analysis. However, despite the variation, all
      studies revealed a degree of association of abnormal LV-GLS with poor cardiac
      outcomes. CONCLUSIONS: Our systematic review of more than 3000 HCM patients
      suggests an association of abnormal LV-GLS with adverse composite cardiac
      outcomes and ventricular arrhythmias.

PMID- 30219396
TI  - Are We Ready to Treat Dilated Cardiomyopathy Differently, Using LGE Guidance?

PMID- 30219397
TI  - Outcome in Dilated Cardiomyopathy Related to the Extent, Location, and Pattern of
      Late Gadolinium Enhancement.
AB  - OBJECTIVES: This study sought to investigate the association between the extent,
      location, and pattern of late gadolinium enhancement (LGE) and outcome in a large
      dilated cardiomyopathy (DCM) cohort. BACKGROUND: The relationship between LGE and
      prognosis in DCM is incompletely understood. METHODS: We examined the association
      between LGE and all-cause mortality and a sudden cardiac death (SCD) composite
      based on the extent, location, and pattern of LGE in DCM. RESULTS: Of 874
      patients (588 men, median age 52 years) followed for a median of 4.9 years, 300
      (34.3%) had nonischemic LGE. Estimated adjusted hazard ratios for patients with
      an LGE extent of 0 to 2.55%, 2.55% to 5.10%, and >5.10%, respectively, were 1.59
      (95% confidence interval [CI]: 0.99 to 2.55), 1.56 (95% CI: 0.96 to 2.54), and
      2.31 (95% CI: 1.50 to 3.55) for all-cause mortality, and 2.79 (95% CI: 1.42 to
      5.49), 3.86 (95% CI: 2.09 to 7.13), and 4.87 (95% CI: 2.78 to 8.53) for the SCD
      end-point. There was a marked nonlinear relationship between LGE extent and
      outcome such that even small amounts of LGE predicted a substantial increase in
      risk. The presence of septal LGE was associated with increased mortality, but SCD
      was most associated with the combined presence of septal and free-wall LGE.
      Predictive models using LGE presence and location were superior to models based
      on LGE extent or pattern. CONCLUSIONS: In DCM, the presence of septal LGE is
      associated with a large increase in the risk of death and SCD events, even when
      the extent is small. SCD risk is greatest with concomitant septal and free-wall
      LGE. The incremental value of LGE extent beyond small amounts and LGE pattern is
      limited.

PMID- 30219398
TI  - Anatomical and Functional Computed Tomography for Diagnosing Hemodynamically
      Significant Coronary Artery Disease: A Meta-Analysis.
AB  - OBJECTIVES: This meta-analysis determined the diagnostic performance of coronary
      computed tomography (CT) angiography (CTA), CT myocardial perfusion (CTP),
      fractional flow reserve CT (FFRCT), the transluminal attenuation gradient (TAG),
      and their combined use with CTA versus FFR as a reference standard for detection
      of hemodynamically significant coronary artery disease (CAD). BACKGROUND: CTA
      provides excellent anatomic, albeit limited functional information for the
      evaluation of CAD. Recently, various functional CT techniques emerged to assess
      the hemodynamic consequences of CAD. METHODS: This meta-analysis was performed in
      adherence to the PRISMA (Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses) guidelines. PubMed, EMBASE, and Web of Science were searched from
      inception until September 7, 2017. Bayesian random effects analysis was used to
      compute pooled sensitivity, specificity, and the summary receiver-operating
      characteristic curve of the index tests and compare them with the FFR as a
      reference standard. Analyses were performed on vessel and patient levels. Because
      CTA has excellent sensitivity, specificity was considered most relevant.
      Individual FFRCT values were collected. RESULTS: Overall, 54 articles and 5,330
      patients were included. At vessel level, pooled specificity of CTP (0.86; 95%
      confidence interval [CI]: 0.76 to 0.93), FFRCT (0.78; 95% CI: 0.72 to 0.83) and
      TAG (0.77; 95% CI: 0.61 to 0.89) were substantially higher than that of CTA
      (0.61; 95% CI: 0.54 to 0.68). The addition of FFRCT, CTP, and TAG to CTA resulted
      in high to excellent specificities (0.80 to 0.92). The summary receiver-operating
      characteristic curve at vessel level yielded superior diagnostic accuracy for
      CTP, FFRCT, and combined CTA and CTP, compared with CTA. A subanalysis of on-site
      versus off-site FFRCT revealed no substantial differences between the sensitivity
      (0.84 vs. 0.85) and specificity (0.80 vs. 0.73) of the 2 techniques. In a second
      subanalysis, dynamic CTP showed higher sensitivity (0.85 vs. 0.72), but had a
      lower specificity (0.81 vs. 0.90) than static CTP. CONCLUSIONS: CTP and FFRCT
      demonstrated a substantial improvement in the identification of hemodynamically
      significant CAD compared with CTA; therefore, their integration to clinical
      workflow before revascularization is recommended.

PMID- 30219399
TI  - A New Decade of Old Questions: Steps Toward Demonstrating the Efficacy of
      Physiologic CAD Evaluation by CT.

PMID- 30219400
TI  - Effect of Early Metoprolol During ST-Segment Elevation Myocardial Infarction on
      Left Ventricular Strain: Feature-Tracking Cardiovascular Magnetic Resonance
      Substudy From the METOCARD-CNIC trial.
AB  - OBJECTIVES: This study sought to evaluate the effect of early intravenous
      metoprolol on left ventricular (LV) strain assessed with feature-tracking
      cardiovascular magnetic resonance (CMR). BACKGROUND: Early intravenous metoprolol
      before primary percutaneous coronary intervention (PCI) in ST-segment elevation
      myocardial infarction (STEMI) portends better outcomes in the METOCARD-CNIC
      (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction)
      trial. METHODS: A total of 197 patients with acute anterior STEMI who were
      enrolled in the METOCARD-CNIC trial (100 allocated to intravenous metoprolol
      before primary PCI and 97 control patients) were evaluated. LV global
      circumferential strain (GCS) and global longitudinal strain (GLS) were measured
      with feature-tracking CMR at 1 week and 6 months after STEMI and compared between
      randomization groups. RESULTS: Patients who received early intravenous metoprolol
      had significantly more preserved LV strain compared with the control patients at
      1 week after STEMI (GCS -13.9 +/- 3.8% vs. -12.6 +/- 3.9%, respectively; p =
      0.013; GLS -11.9 +/- 2.8% vs. -10.9 +/- 3.2%, respectively; p = 0.032). In both
      groups, LV strain significantly improved during follow-up (mean difference
      between 6-month and 1-week strain for the metoprolol group: GCS -2.9%, 95%
      confidence interval [CI]: -3.5% to -2.4%; GLS: -2.9%, 95% CI: -3.4% to -2.4%;
      both p < 0.001; the control group: GCS -3.4%, 95% CI: -3.9% to -2.8%; GLS -3.4%,
      95% CI: -3.9% to -3.0%; both p < 0.001). When dividing the overall cohort of
      patients in quartiles of GCS and GLS, there were significantly fewer patients in
      the first quartile (i.e., the worst LV systolic function) who received early
      intravenous metoprolol compared with control patients at 1 week and 6 months (p <
      0.05 for GCS and GLS at both time points). CONCLUSIONS: In patients with anterior
      STEMI, early administration of intravenous metoprolol before primary PCI was
      associated with significantly fewer patients with severely depressed LV GCS and
      GLS, both at 1 week and 6 months. Feature-tracking CMR represents a complementary
      tool to evaluate the benefits of cardioprotective therapies. (Effect of
      METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion [METOCARD
      CNIC]: NCT01311700).

PMID- 30219401
TI  - Impaired Cardiac Reserve and Abnormal Vascular Load Limit Exercise Capacity in
      Chronic Thromboembolic Disease.
AB  - OBJECTIVES: This study was a comprehensive evaluation of cardiopulmonary function
      in patients with chronic thromboembolic (pulmonary vascular) disease (CTED)
      during exercise. BACKGROUND: Exertional dyspnea is frequent following pulmonary
      embolism, but only a minority of patients eventually develops chronic
      thromboembolic pulmonary hypertension (CTEPH). Better understanding of the
      factors that limit exercise capacity in patients with persistent pulmonary artery
      obstruction could help to further define the entity of CTED. METHODS: Fifty-two
      subjects (13 healthy control subjects, 14 CTED patients, and 25 CTEPH patients)
      underwent cardiopulmonary exercise testing and exercise cardiac magnetic
      resonance with simultaneous invasive pressure registration. Pulmonary vascular
      function and right ventricular contractile reserve were assessed through combined
      invasive pressure measurements and magnetic resonance imaging volume measures.
      RESULTS: Exercise capacity was reduced by 29% and 57% in patients with CTED and
      CTEPH respectively, compared with control subjects. Both CTED (3.48
      [interquartile range: 2.24 to 4.36] mm Hg * l-1 * min-1) and CTEPH patients (8.85
      [interquartile range: 7.18 to 10.4] mm Hg * l-1 * min-1) had abnormal total
      pulmonary vascular resistance. Right ventricular contractile reserve was reduced
      in CTED patients compared with control subjects (2.23 +/- 0.55 vs. 3.72 +/-
      0.94), but was still higher than that in CTEPH patients (1.34 +/- 0.24; p <
      0.001). As opposed to patients with CTEPH in whom right ventricular ejection
      fraction declined with exercise, right ventricular ejection fraction still
      increased in patients with CTED, albeit to a lesser extent than in healthy
      control subjects (interaction p < 0.001), which illustrated the distinct patterns
      of ventricular-arterial coupling. CONCLUSIONS: CTED represents an intermediate
      clinical phenotype. Exercise imaging unmasks cardiovascular dysfunction not
      evident at rest and identifies hemodynamically significant disease that results
      from reduced contractile reserve or increased vascular load.

PMID- 30219402
TI  - Novel Use for Intracardiac Echocardiography: Evaluation of Patients With
      Continuous Flow Left Ventricular Assist Devices.

PMID- 30219404
TI  - Prevalence and Significance of Tricuspid Regurgitation Post-Endocardial Lead
      Placement.

PMID- 30219403
TI  - Navigating a Career in Structural Heart Disease Interventional Imaging.

PMID- 30219405
TI  - 3-Dimensional Echocardiography: Moving From Pretty Pictures toward Patient
      Outcomes.

PMID- 30219406
TI  - Not Quite Chronic Thromboembolic Pulmonary Hypertension But More Than a SOB
      Story.

PMID- 30219407
TI  - Pulmonary Venous Waveforms Predict Rehospitalization and Mortality After
      Percutaneous Mitral Valve Repair.
AB  - OBJECTIVES: In this study, the authors hypothesized that intraprocedural
      improvement of pulmonary venous (PV) waveforms are predictive of improved
      outcomes. In this report, they analyzed intraprocedural invasive and
      echocardiographic changes with respect to rehospitalization and mortality.
      BACKGROUND: The effects of hemodynamic changes during percutaneous mitral valve
      repair (PMVR) with MitraClip (Abbott Vascular, Santa Clara, California) are
      incompletely characterized. METHODS: The authors retrospectively reviewed records
      and intraprocedural transesophageal echocardiograms of 115 consecutive patients
      (age 76 +/- 12 years) who underwent PMVR for mitral regurgitation (MR) from May
      2013 to January 2017 at Emory University Hospital. They assessed intraprocedural
      PV waveforms for improvement in morphology, measured change in MR grade by
      semiquantitative methods, evaluated invasive changes in left atrial pressure
      (LAP) and V-wave, and compared with 30-day and 1-year rehospitalization and all
      cause mortality. RESULTS: Ninety-three cases (80%) had PV waveforms before and
      after clip placement sufficient for analysis, of which 67 (73%) demonstrated
      intraprocedural improvement in PV morphology and 25 (27%) did not. At 24 months,
      57 (85%) of those with PV improvement were living, compared with only 10 (40%) of
      those without improvement. Proportional hazards models demonstrated a significant
      survival advantage in those with PV improvement (hazard ratio [HR] = 0.28, 95%
      confidence interval [CI] 0.08 to 0.93, p = 0.038). By multivariable analysis, PV
      improvement predicted reduced 1-year cardiac rehospitalization (odds ratio [OR] =
      0.18, p = 0.044). Intraprocedural assessment of MR grade and invasive
      hemodynamics did not consistently predict mortality and rehospitalization.
      CONCLUSIONS: PV waveforms are important markers of procedural success after PMVR.
      Our data show intraprocedural PV waveforms may predict rehospitalization and
      mortality after PMVR. A larger, multicenter cohort will be important to clarify
      this relationship.

PMID- 30219408
TI  - Added Value of 3- Versus 2-Dimensional Echocardiography Left Ventricular Ejection
      Fraction to Predict Arrhythmic Risk in Patients With Left Ventricular
      Dysfunction.
AB  - OBJECTIVES: The study sought to evaluate the potential clinical impact of using 3
      dimensional echocardiography (3DE) to measure left ventricular ejection fraction
      (LVEF) in patients considered for implantable cardioverter-defibrillator (ICD)
      implantation and to assess the predictive value of 3DE LVEF for arrhythmic
      events. BACKGROUND: ICD therapy is currently recommended to prevent sudden
      cardiac death in patients with symptomatic heart failure and LVEF <=35%, and in
      asymptomatic patients with ischemic heart disease and LVEF <=30%. Two-dimensional
      echocardiography (2DE) is currently used to calculate LVEF. However, 3DE has been
      reported to be more reproducible and accurate than 2DE to measure LVEF. METHODS:
      The study prospectively enrolled 172 patients with LV dysfunction (71% ischemic).
      Both 2DE and 3DE LVEF were obtained during the same study. The outcome was the
      occurrence of major arrhythmic events (sudden cardiac death, aborted cardiac
      arrest, appropriate ICD therapy). RESULTS: After a median follow up of 56 (range
      18 to 65) months, major arrhythmic events occurred in 30% of the patients.
      Compared with 2DE, 3DE changed the assignment above or below the LVEF thresholds
      for ICD implantation in 20% of patients, most of them having 2DE LVEFs within +/-
      10% from threshold. By cause-specific hazard model, 3DE LVEF was the only
      independent predictor of the occurrence of major arrhythmic events. CONCLUSIONS:
      LVEF by 3DE was an independent predictor of major arrhythmic events and improved
      arrhythmic risk prediction in patients with LV dysfunction. When compared with
      2DE LVEF, 3DE measurement of LVEF may change the decision to implant an ICD in a
      sizable number of patients.

PMID- 30219409
TI  - Strain by Feature Tracking: A Short Summary of the Journey of CMR in STEMI.

PMID- 30219410
TI  - Drug-fortified liposomes as carriers for sustained release of NSAIDs: The concept
      and its validation in the animal model for the treatment of arthritis.
AB  - Drug-fortified cationic liposomes of 6-methoxy-2-naphthylacetic acid (6-MNA) were
      prepared and characterized by various techniques. The residence time of drug
      fortified liposomes in joint cavity was evaluated by intra-articular (IA)
      administration of the radio-labeled (99mTc) liposomal formulation in the inflamed
      joints in rats. The cationic liposomal formulation composed of 6-MNA (3) as an
      active agent, its double salt (4) with the lipid 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine (DSPE), and pharmaceutically acceptable excipients such as
      hydrogenated soyabean phospatidylcholine (HSPC) and 1,2-dioleyloxy-3
      trimethylammoniumpropane chloride (DOTAP) were developed using thin film
      hydration technique. The cryo-TEM analysis confirmed that the prepared optimized
      liposomal formulation (DFL-2) was a mixture of small unilamellar vesicles (SUVs),
      large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). In addition,
      the TEM analysis confirmed that the prepared liposomes were of spherical in shape
      having liposome size in the range of 500-900 nm and zeta potential of about +30
      mV. The developed cationic liposomes exhibited sustained release profile of
      payload of 6-MNA for over >12 h and about five times higher retention in the
      inflamed animal joints after 24 h (by scintigraphy of the joints) as compared to
      the plain 6-MNA solution when administered by IA route. The anti-inflammatory
      activity of prepared liposomal composition is evaluated by Freund's adjuvant
      induced arthritic model in rats. The liposomal formulation was well tolerated by
      all animals indicating good biocompatibility. Further, the cationic liposomal
      formulation treated group showed decreased erythrocyte sedimentation rate (ESR),
      and C-reactive protein (CRP) level in comparison to the control and the standard
      groups in the in vivo study. The improved efficacy of the drug-fortified
      liposomal formulation was due to the coupled effect of longer retention and
      sustained release of the active drug 6-MNA in the joints. From the obtained
      results it could be concluded that the combined effect of the cationic charge on
      the drug-fortified liposomes and the inherent affinity of the active agent
      towards the synovial joint tissues, coupled with slow release of the active drug
      due to double salt approach at the site of administration could potentially
      decrease the frequency of IA drug administration. Hence such a formulation could
      prove to be a therapeutic boon for the management of late stage arthritis.

PMID- 30219411
TI  - Can categorical knowledge be used in visual search?
AB  - Smith, Redford, Gent, and Washburn (2005) have proposed a new categorization
      paradigm called the visual-search categorization task to study how display size
      affects categorization performance. Their results show that, in a wide range of
      conditions, category knowledge collapses as soon as multiple stimuli are
      simultaneously displayed in a scene. This result is surprising and important
      considering that humans parse and categorize objects from complex scenes on a
      daily basis. However, Smith et al. only studied one kind of category structure.
      This article presents the results of three experiments exploring the effect of
      display size on perceptual categorization as a function of category structure. We
      show that rule-based and information-integration categories are differently
      affected by display size in the visual search categorization task. For rule-based
      structures, target-present and target-absent trials are not much affected by
      display size. However, the effect of display size is bigger for information
      integration category structures, and much more pronounced for target-absent
      trials than for target-present trials. A follow-up experiment shows that target
      redundancy (i.e., having more than one target in the display) does not improve
      performance with information-integration category structures. These results
      suggest that categories may be learned differently depending on their underlying
      structure, and that the resulting category representation may influence
      performance in the visual search categorization task.

PMID- 30219413
TI  - [Inflammasome, interleukin-1, autoinflammatory diseases and neutrophilic
      dermatosis].

PMID- 30219412
TI  - My true face: Unmasking one's own face representation.
AB  - Face recognition has been the focus of multiple studies, but little is still
      known on how we represent the structure of one's own face. Most of the studies
      have focused on the topic of visual and haptic face recognition, but the metric
      representation of different features of one's own face is relatively unknown. We
      investigated the metric representation of the face in young adults by developing
      a proprioceptive pointing task to locate face landmarks in the first-person
      perspective. Our data revealed a large overestimation of width for all face
      features which resembles, in part, the size in somatosensory cortical
      representation. In contrast, face length was compartmentalised in two different
      regions: upper (underestimated) and bottom (overestimated); indicating size
      differences possibly due to functionality. We also identified shifts of the
      location judgments, with all face areas perceived closer to the body than they
      really were, due to a potential influence of the self-frame of reference. More
      importantly, the representation of the face appeared asymmetrical, with an
      overrepresentation of right side of the face, due to the influence of
      lateralization biases for strong right-handers. We suggest that these effects may
      be due to functionality influences and experience that affect the construction of
      face structural representation, going beyond the parallel of the somatosensory
      homunculus.

PMID- 30219414
TI  - Rhabdoid type intramedullary meningioma. A case report and review of the
      literature.
AB  - Meningiomas are the most frequent tumors located at the spinal level together
      with neurinomas and metastases. These tumors tend to be intradural and
      extramedullar. There are few cases described in the literature with a purely
      intramedullary location (less than 10 cases) and they are frequently observed in
      the union craneal-cervical. In the presence of an intramedullary tumor we perform
      differential diagnoses with ependymomas, astrocytomas... In this article we
      present the first case described in the literature of a patient with a rabdoid
      type meningioma exclusively intramedullary at the level of the medullary cone.

PMID- 30219415
TI  - Isolation and identification of Treponema pedis and Treponema phagedenis-like
      organisms from bovine digital dermatitis lesions found in dairy cattle in Turkey.
AB  - The isolation and identification of microorganisms associated with digital
      dermatitis (DD) in Turkish dairy cattle was investigated using punch skin biopsy
      samples from typical clinical lesions; they were collected from dairy farms and
      abattoirs in 5 different geographical locations in Turkey. Morphological
      characteristics and flagellation types were examined using a transmission
      electron microscope, and their enzyme profiles by enzyme activation kits; their
      catalase reaction characteristics were evaluated by the addition of 3% H2O2.
      Their phylogenies were identified using 16S rRNA and the results compared with
      known gene bank data. Bacterial cells were 5.0 to 18.2 um long, 0.2 to 0.5 um
      wide, and their minimum number of periplasmic flagellum was 4 (4:8:4) with a
      maximum of 8 (8:16:8). All isolates were catalase negative. Of the spirochetes
      isolated and identified, group I organisms showed close similarity with Treponema
      pedis (99% genetic homology), whereas those in group II were similar to Treponema
      phagedenis (98% homology). This is the first report of specific sub-groups of
      Treponema spp., isolated from Turkish dairy cattle presenting with DD lesions,
      being associated with this disease; these morphotypes were similar to those found
      globally in housed dairy cattle units and are probably significant microorganisms
      associated with the aetiopathogensis of this infectious disease causing acute
      bovine lameness. These results suggest that the distribution of DD-associated
      treponemes is not specific to particular geographic regions of Turkey.

PMID- 30219416
TI  - Study of the efficacy of a Streptococcus uberis mastitis vaccine against an
      experimental intramammary infection with a heterologous strain in dairy cows.
AB  - Streptococcus uberis is a worldwide pathogen that causes intramammary infections
      in dairy cattle. Nevertheless, commercial vaccines are currently not available
      and measures to control S. uberis mastitis are limited to the implementation of
      good management practices. The aim of the present study was to evaluate the
      efficacy of an S. uberis subunit vaccine against bovine mastitis (Laboratorios
      Hipra S.A., Amer, Spain) administered precalving against an experimental
      intramammary challenge with a heterologous S. uberis strain in dairy cows
      postcalving. With this objective, 25 gestating Holstein-Friesian heifers were
      randomly assigned to 1 of 2 groups: group 1 (n = 13), vaccinated by intramuscular
      route with the vaccine, and group 2 (n = 12), vaccinated by intramuscular route
      with phosphate-buffered saline as a control group. Both groups were immunized 60
      and 21 d before the expected parturition date (75 and 36 d before challenge).
      Fourteen days after calving all cows were challenged by intramammary infusion of
      100 colony-forming units of a heterologous S. uberis strain in 2 quarters per
      cow. Then, challenged quarters were monitored for clinical signs of mastitis,
      bacterial count, and somatic cell count for the following 21 d. Rectal
      temperature and daily milk yield per cow were also assessed. Results showed that
      all challenged quarters developed clinical mastitis. Nevertheless, vaccination
      significantly reduced the clinical signs of mastitis, bacterial count, rectal
      temperature, and daily milk yield losses after the intramammary infection and
      significantly increased the number of quarters with no bacterial isolation and
      somatic cell count <200,000 cells/mL at the end of the study (d 19, 20, and 21
      after challenge). To confirm the efficacy of this vaccine, further studies under
      field conditions are needed.

PMID- 30219417
TI  - Genetic and nongenetic profiling of milk pregnancy-associated glycoproteins in
      Holstein cattle.
AB  - Pregnancy-associated glycoproteins (PAG) are secreted by the trophoblast and are
      detectable in maternal circulation around the time of attachment of the fetal
      placenta, as well as in blood and milk throughout gestation. The understanding of
      the genetic mechanisms controlling PAG levels can confer advantages for livestock
      breeding programs given the precocity and the ease of obtaining this phenotype
      from routine pregnancy diagnosis. The aim of this study was to characterize PAG
      levels by estimating genetic parameters and correlations with other dairy traits,
      and to identify genomic regions and candidate genes associated with PAG levels in
      milk. The PAG data consisted of pregnancy diagnoses using commercial assays from
      2012 to 2017, and genotype data consisted of 54,123 SNP markers for 2,352
      individuals (embryos and dams). The model included contemporary group (herd,
      year, and season) and embryo age as fixed effects, and random embryonic (direct)
      and maternal (indirect) genetic effects. Using genomic data, the estimated
      heritability for direct and maternal genetic effects (+/- standard deviations)
      were 0.23 +/- 0.05 and 0.11 +/- 0.05, respectively. The genetic correlation
      between these effects was almost zero (0.001 +/- 0.06). A preliminary analysis
      revealed low correlations between milk PAG levels and other dairy traits. The
      genome-wide association analysis was performed using 2 approaches: single-marker
      and single-step using all markers. Four genomic regions with direct genetic
      effects were detected on Bos taurus autosome (BTA) 6, BTA7, BTA19, and BTA29 of
      the embryonic genome. The BTA29 locus was within the bovine PAG gene cluster,
      suggesting a cis-regulatory quantitative trait locus on the PAG expression.
      However, other associations, without an obvious link to PAG expression, could be
      related to the transportation of PAG and their concentration in milk. Only 1
      region from the maternal genome, on BTA4, had a significant indirect effect,
      where WNT2 is a candidate gene related to placenta vascularization and gestation
      health. Collectively, our results suggest a moderate genetic control of milk PAG
      levels from both maternal and fetal genomes, but larger studies are needed to
      fully evaluate the usefulness of milk PAG in the genetic evaluation of fetal
      growth and cow fertility.

PMID- 30219418
TI  - Development of an in vitro method to determine rumen undigested aNDFom for use in
      feed evaluation.
AB  - A portion of the forage cell wall, defined as neutral detergent fiber (NDF), is
      indigestible to anaerobic microbial digestion in ruminants. This fraction has
      been characterized by surface area relationships between acid detergent lignin,
      but recently, data have been published describing the dynamic nature of this
      relationship. In situ approaches have been described to estimate indigestible
      NDF, recovering the undigested NDF after long-term fermentations (uNDF). To be
      applicable to nutritionists and diet formulation, determining uNDF needs to be
      conducted in a commercial laboratory similar to other routine analyses of forage
      chemistry. A series of studies were conducted to evaluate an in vitro approach,
      to describe uNDF, which is repeatable and adaptable for routine feed evaluation.
      One hundred and two forages of several species were analyzed for NDF, acid
      detergent lignin, and uNDF. The uNDF was estimated by several approaches
      involving long-term fermentations and filtration steps to evaluate the length of
      time necessary to exhaust the digestible NDF and a filtration method necessary to
      maintain sample integrity by ensuring low sample loss and uniform recovery with
      residues from long-term in vitro fermentation. To determine uNDF, in vitro
      fermentations were conducted on 0.50 or 0.75 g of dry matter samples, in
      triplicate, at multiple time points up to 504 h and initially used Gooch
      crucibles with Celite (Thermo Fisher Scientific, Waltham, MA) as a filtering aid.
      The final method utilized a 1.5-um pore size glass microfiber filter, which
      allowed for increased repeatability and improved sample recovery (lowest standard
      deviation). In this study, in vitro fermentations of 240 h were adequate to
      characterize and identify uNDF, which was repeatable among conventional forages
      provided the samples, after NDF analyses, were filtered through the same glass
      fiber filter. This approach could be adapted by commercial laboratories and would
      provide opportunities to develop near-infrared reflectance spectroscopy equations
      and calibrations.

PMID- 30219419
TI  - Seryl-tRNA synthetase-mediated essential amino acids regulate beta-casein
      synthesis via cell proliferation and mammalian target of rapamycin (mTOR)
      signaling pathway in bovine mammary epithelial cells.
AB  - Essential amino acids (EAA) play an important role in promoting milk protein
      synthesis in primary bovine mammary epithelial cells (BMEC). However, the
      regulatory mechanisms involved in the relationship between EAA and milk protein
      synthesis have not been fully explored. This study examined the effects of seryl
      tRNA synthetase (SARS) on EAA-stimulated beta-casein synthesis, cell
      proliferation, and the mammalian target of rapamycin (mTOR) system in BMEC.
      First, BMEC were cultured in medium either lacking all EAA (-EAA) or that
      included all EAA (+EAA) for 12 h. The BMEC were then supplemented with the
      opposing treatments (-EAA supplemented with +EAA and vice versa) for 0 h, 10 min,
      0.5 h, 1 h, 6 h, or 12 h, respectively. After the treatment-specific time
      allotment, proteins were collected for Western blotting. Subsequently, a 2 * 2
      factorial design was used to evaluate the interactive of SARS inhibition (control
      or SARS inhibited) and EAA supply (+EAA or -EAA) on gene and protein abundance,
      cell viability, and cell cycle in BMEC. Based on the data obtained in the first
      experiment, the changes in protein abundance of beta-casein and SARS depended on
      EAA treatment time in similar patterns. The protein abundance of beta-casein,
      SARS, and mammalian target of rapamycin (mTOR)-related proteins, cell viability,
      cell cycle progression, and the mRNA abundance of cyclin D1 (CCND1, cell cycle
      progression marker) and marker of proliferation Ki-67 (MKI67, cell proliferation
      marker) were stimulated by the presence of EAA. Correspondingly, when cells were
      deprived of EAA, cell proliferation and abundance of these proteins and genes
      were reduced overall. Moreover, the decreases in these aspects were further
      exacerbated by inhibiting SARS, suggesting that an interaction between EAA and
      SARS is important for regulating protein synthesis. The results indicated that
      SARS stimulated the mTOR signaling pathway when EAA were present, enhanced EAA
      stimulated cell proliferation, and contributed to increased beta-casein
      production in BMEC.

PMID- 30219420
TI  - Rapid and sensitive detection of Escherichia coli O157:H7 using coaxial channel
      based DNA extraction and microfluidic PCR.
AB  - In this study, a rapid and sensitive method for detection of Escherichia coli
      O157:H7 using the coaxial channel-based DNA extraction and the microfluidic PCR
      was proposed and verified. The magnetic silica beads were first pumped into the
      coaxial channel, which was captured in the coaxial channel more uniformly by
      applying the multiring high-gradient magnetic field. After the E. coli O157:H7
      cells were lysed with the lysis buffer to release the DNA, the improved coaxial
      channel was used to efficiently extract the DNA, followed by washing with ethanol
      to remove the residual proteins and eluting with a small volume of deionized
      water to obtain the purified and concentrated DNA. Finally, the obtained DNA was
      amplified and determined using the microfluidic PCR. This proposed bacteria
      detection method was able to detect E. coli O157:H7 as low as 12 cfu/mL when the
      large volume (10 mL) of bacterial sample was used, and the recovery of E. coli
      O157:H7 in the spiked milk samples ranged from 97.4 to 100.6%. This proposed
      bacteria detection method has shown great potential to detect lower concentration
      of E. coli O157:H7 from larger volumes of sample.

PMID- 30219421
TI  - Genetic selection for hoof health traits and cow mobility scores can accelerate
      the rate of genetic gain in producer-scored lameness in dairy cows.
AB  - Cattle breeding programs that strive to reduce the animal-level incidence of
      lameness are often hindered by the availability of informative phenotypes. As a
      result, indicator traits of lameness (i.e., hoof health and morphological
      conformation scores) can be used to improve the accuracy of selection and
      subsequent genetic gain. Therefore, the objectives of the present study were to
      estimate the variance components for hoof health traits using various phenotypes
      collected from a representative sample of Irish dairy cows. Also of interest to
      the present study was the genetic relationship between both hoof health traits
      and conformation traits with producer-scored lameness. Producer-recorded lameness
      events and linear conformation scores from 307,657 and 117,859 Irish dairy cows,
      respectively, were used. Data on hoof health (i.e., overgrown sole, white line
      disease, and sole hemorrhage), mobility scores, and body condition scores were
      also available from a research study on up to 11,282 Irish commercial dairy cows.
      Linear mixed models were used to quantify variance components for each trait and
      to estimate genetic correlations among traits. The estimated genetic parameters
      for hoof health traits in the present study were greater (i.e., heritability
      range: 0.005 to 0.27) than previously reported in dairy cows. With the exception
      of analyses that considered hoof health traits in repeatability models, little
      difference in estimated variance components existed among the various hoof-health
      phenotypes. Results also suggest that producer-recorded lameness is correlated
      with both hoof health (i.e., genetic correlation up to 0.48) and cow mobility
      (i.e., genetic correlation = 0.64). Moreover, cows that genetically tend to have
      rear feet that appear more parallel when viewed from the rear are also
      genetically more predisposed to lameness (genetic correlation = 0.39); genetic
      correlations between lameness and other feet and leg type traits, as well as
      between lameness and frame type traits, were not different from zero. Results
      suggest that if the population breeding goal was to reduce lameness incidence,
      improve hoof health, or improve cow mobility, genetic selection for either of
      these traits should indirectly benefit the other traits. Results were used to
      quantify the genetic gains achievable for lameness when alternative phenotypes
      are available.

PMID- 30219422
TI  - The genetic architecture of milk ELISA scores as an indicator of Johne's disease
      (paratuberculosis) in dairy cattle.
AB  - Johne's disease (or paratuberculosis), caused by Mycobacterium avium ssp.
      paratuberculosis (MAP) infection, is a globally prevalent disease with severe
      economic and welfare implications. With no effective treatment available,
      understanding the role of genetics influencing host infection status is essential
      to develop selection strategies to breed for increased resistance to MAP
      infection. The main objectives of this study were to estimate genetic parameters
      for the MAP-specific antibody response using milk ELISA scores in Canadian
      Holstein cattle as an indicator of resistance to Johne's disease, and to unravel
      genomic regions and candidate genes significantly associated with MAP infection.
      After data editing, 168,987 milk ELISA records from 2,306 herds, obtained from
      CanWest Dairy Herd Improvement, were used for further analyses. Variance and
      heritability estimates for MAP infection status were determined using univariate
      linear animal models under 3 scenarios: (a) SCEN1: the complete data set (all
      herds); (b) SCEN2: herds with at least one suspect or test-positive animal (ELISA
      optical density >=0.07); and (c) SCEN3: herds with at least one test-positive
      animal (ELISA optical density >=0.11). Heritability estimates were calculated as
      0.066, 0.064, and 0.063 for SCEN1, SCEN2, and SCEN3, respectively. The
      correlations between estimated breeding values for resistance to MAP infection
      and other economically important traits, when significant, were favorable and of
      low magnitude. Genome-wide association analyses identified important genomic
      regions on Bos taurus autosome (BTA)1, BTA7, BTA9, BTA14, BTA15, BTA17, BTA19,
      and BTA25 showing significant association with MAP infection status. These
      regions included 2 single nucleotide polymorphisms located 2 kb upstream of
      positional candidate genes CD86 and WNT9B, which play key roles in host immune
      response and tissue homeostasis. This study revealed the genetic architecture of
      MAP infection in Canadian Holstein cattle as measured by milk ELISA scores by
      estimating genetic parameters along with the identification of genomic regions
      potentially influencing MAP infection status. These findings will be of
      significant value toward implementing genetic and genomic evaluations for
      resistance to MAP infection in Holstein cattle.

PMID- 30219423
TI  - Technical note: Rapid mineral determination in forages by X-ray fluorescence.
AB  - A large portion of the cow's ration is composed of forages that can vary greatly
      in mineral concentrations, which may affect animal performance and health.
      Current methods for mineral analysis require sample destruction either through
      wet or dry ashing and complex analytical techniques for individual minerals.
      Energy dispersive X-ray fluorescence (EDXRF) is a nondestructive, multi-mineral,
      spectroscopy technique, which makes mineral quantification simple, direct, and
      affordable. The study objective was to evaluate the prediction performance of
      EDXRF of Na, Mg, P, S, Cl, Ca, K, Mn, Fe, Cu, and Zn concentrations in forages.
      Twelve certified plant samples with a wide range in mineral concentrations were
      used to develop calibrations, and 35 forages (18 alfalfa hays, 10 grass hays, 7
      corn silages) with measured mineral concentrations, which were collected over
      several years from 3 proficiency programs, were used as an independent validation
      set. All the samples were previously dried and finely ground and were prepared by
      compressing them into a round dense pellet, 40 mm in diameter, using a 40-ton
      pneumatic laboratory press. Samples were scanned using an EDXRF instrument
      enhanced for lighter minerals like Na and Mg. Samples were scanned at 20 keV and
      at 40 KeV associated with an Al filter, for a total analysis time of
      approximately 6 min. Calibrations were developed with Bruker SpectraEDX (Bruker,
      Hamburg, Germany) software and optimized to minimize the standard error of
      calibration. All of the minerals had acceptable calibration performance with
      coefficient of determination ranging from 0.93 (P) and 0.99 (Cl, Ca, and Mn) and
      coefficients of variation within 5 to 14%, which are similar to the coefficients
      of variation of the reference analysis. The coefficients of variation for Na was
      an exception, with a coefficients of variation of 29%. The validation set
      obtained similar statistical results as that observed in calibration. The root
      mean square error of prediction corrected for bias was similar to the standard
      error of calibration, indicating that it is possible to build a robust
      calibrations that performed well across different type of forages by using 12
      reference samples with a sufficient range in mineral concentrations that were
      determined accurately. A bias correction was necessary to improve prediction
      accuracy only for K (-0.23% dry matter) and Ca (-0.16% dry matter). Energy
      dispersive X-ray fluorescence demonstrated the ability to be an accurate, direct,
      and simple technique for forage mineral analysis.

PMID- 30219424
TI  - The effect of the forage-to-concentrate ratio of the partial mixed ration and the
      quantity of concentrate in an automatic milking system for lactating Holstein
      cows.
AB  - This study was conducted to evaluate the effects of the forage-to-concentrate
      ratio of the partial mixed ration (PMR) and the quantity of concentrate offered
      in an automated milking system (AMS), in a feed-first guided-flow barn, on the
      behavior and performance of dairy cows. Eight ruminally cannulated multiparous
      Holstein cows were used in a replicated 4 * 4 Latin square balanced for carry
      over effects. Treatments were arranged in a 2 * 2 factorial consisting of a PMR
      that contained (dry matter basis) either a low (54:46; L-FOR) or a high (64:36; H
      FOR) forage-to-concentrate ratio and AMS concentrate provision to achieve low (2
      kg/d; L-AMS) or high (6 kg/d; H-AMS) intake. Each period consisted of 28 d with 6
      d for dietary transition, 13 d for adaptation, and 9 d of collection. The first 4
      d of data and sample collection were used to evaluate behavioral data (milking
      frequency, feeding behavior, and standing and lying behavior) and ruminal pH.
      Subsequently, a sampling device removal day was provided, and the last 4 d were
      used to evaluate ruminal fermentation and apparent total-tract digestibility. All
      9 d were used for milk yield measurement, and the 8 d were used for dry matter
      intake measurement. Cows fed the H-AMS consumed 3.5 kg/d less PMR while consuming
      4.2 kg/d more AMS concentrate, but total dry matter intake (PMR+AMS) was not
      affected by treatments averaging 27.3 kg/d. Although cows fed H-AMS had greater
      concentrate intake, they also had greater variability for AMS concentrate intake
      among days (0.85 vs. 0.25 kg/d, respectively). The number of PMR meals and PMR
      eating behavior were not affected by the PMR or AMS treatments. Feeding H-AMS did
      not affect milking frequency averaging 3.63 milkings/d, but tended to increase
      milk yield by 1.25 kg/d relative to L-AMS. Likewise, cows fed the L-FOR tended to
      have greater milk yield relative to H-FOR (39.3 vs 37.9 kg/d, respectively), but
      had greater holding area time. Minimum ruminal pH tended to be lower for cows fed
      L-FOR compared with cows fed H-FOR but was not affected by the AMS concentrate
      treatment. When fed the L-FOR, feeding the H-AMS increased total short-chain
      fatty acid concentration in the rumen relative to cows fed L-AMS, whereas the
      response for H-FOR was not affected by the AMS concentrate. These data suggest
      that feeding H-AMS may improve milk yield, but also increases the day-to-day
      variability in AMS concentrate consumption. Feeding a L-FOR PMR may increase milk
      yield without affecting variability in AMS concentrate consumption; however, it
      may reduce ruminal pH and increase the time spent in the holding area compared
      with cows fed a H-FOR PMR.

PMID- 30219425
TI  - Short communication: Confirmation of candidate causative variants on milk
      composition and cheesemaking properties in Montbeliarde cows.
AB  - In a previous study, we identified candidate causative variants located in 24
      functional candidate genes for milk protein and fatty acid composition in
      Montbeliarde, Normande, and Holstein cows. We designed these variants on the
      custom part of the EuroG10K BeadChip (Illumina Inc., San Diego, CA), which is
      routinely used for genomic selection analyses in French dairy cattle. To validate
      the effects of these candidate variants on milk composition and to estimate their
      effects on cheesemaking properties, a genome-wide association study was performed
      on milk protein, fatty acid and mineral composition, as well as on 9 cheesemaking
      traits (3 laboratory cheese yields, 5 coagulation traits, and milk pH). All the
      traits were predicted from midinfrared spectra in the Montbeliarde cow population
      of the Franche-Comte region. A total of 194 candidate variants located in 24
      genes and 17 genomic regions were imputed on 19,862 cows with phenotypes and
      genotyped with either the BovineSNP50 (Illumina Inc.) or the EuroG10K BeadChip.
      We then tested the effect of each SNP in a mixed linear model including random
      polygenic effects estimated with a genomic relationship matrix. We confirm here
      the effects of candidate causative variants located in 17 functional candidate
      genes on both cheesemaking properties and milk composition traits. In each
      candidate gene, we identified the most plausible causative variant: 4 are
      missense in the ALPL, SLC26A4, CSN3, and SCD genes, 7 are located in 5'UTR
      (AGPAT6), 3' untranslated region (GPT), or upstream (CSN1S1, CSN1S2, PAEP, DGAT1,
      and PICALM) regions, and 6 are located in introns of the SLC37A1, MGST1, CSN2,
      BRI3BP, FASN, and ANKH genes.

PMID- 30219426
TI  - Associations of subclinical hypocalcemia with fertility in a herd of grazing
      dairy cows.
AB  - The main objective was to assess the associations of subclinical hypocalcemia
      (SCH), diagnosed at parturition (SCH-0) and 7 d in milk (SCH-7), with fertility
      in a herd of grazing dairy cows. Additional objectives were to characterize Ca
      concentration on 0 and 7 d in milk (DIM), assessing the risk factors for SCH-0
      and SCH-7 and also the relationship with health status (metritis, endometritis,
      subclinical ketosis, and culling). A prospective observational study was carried
      out in a dairy farm in Argentina. Holstein cows (n = 126) were body condition
      scored (BCS, 1-5) on -21 +/- 3, 0, 7 +/- 3, and 28 +/- 7 DIM and blood was
      collected on 0 and 7 +/- 3 DIM to determine Ca and beta-hydroxybutyrate
      concentrations. Calcium concentrations <2.0 and <2.14 mmol/L were used to define
      SCH-0 and SCH-7, respectively. The associations of SCH with (1) the odds for
      pregnancy to first service (P1AI) and pregnancy by 100 DIM (P100) were evaluated
      by logistic models, (2) the services per pregnancy was evaluated by a Poisson
      regression model, and (3) the hazards of insemination and pregnancy were
      evaluated with proportional hazards regression models whereas median days from
      calving to first insemination and to pregnancy were estimated by Kaplan-Meier
      method. Additionally, Ca concentration was assessed by linear regression models,
      and the associations of SCH-0 and SCH-7 with the odds for metritis, endometritis,
      subclinical ketosis, and culling were evaluated by logistic models. Calcium
      concentrations were similar at 0 and 7 DIM (2.40 vs. 2.41 mmol/L, respectively);
      they were higher in cows calving in fall than in summer (2.58 vs. 2.24 mmol/L),
      and they also were higher in primiparous than in multiparous cows (2.53 vs. 2.28
      mmol/L, respectively). The proportion of cows having SCH-0 and SCH-7 was 27.3 and
      39.3%, respectively. Fall-calving cows had lower odds for SCH-0 [odds ratio (OR)
      = 0.31, 95% confidence interval (CI) = 0.12-0.86] than summer-calving cows,
      multiparous cows had higher odds for SCH-0 (OR = 3.96, 95% CI = 1.09-14.39) than
      primiparous cows, and cows with prepartum BCS >=3.00 had higher odds for SCH-0
      (OR = 4.03, 95% CI = 1.17-13.89) than in cows with BCS <3.00. Conversely, parity
      and prepartum BCS were not important predictors for SCH-7. Surprisingly, SCH-0
      was not a risk factor for SCH-7. Cows with SCH-0 had lower odds for P1AI (OR =
      0.26, 95% CI = 0.07-0.99) than normocalcemic cows, given that P1AI was 14 versus
      38%, respectively. The hazard of first service was not associated with SCH-0
      (hazard ratio = 1.03, 95% CI = 0.63-1.70) but cows with SCH-0 had lower hazard of
      pregnancy (hazard ratio = 0.39, 95% CI = 0.16-0.98) and took 32 d longer to get
      pregnant (105 vs. 73) than normocalcemic cows. Conversely, SCH-7 was not
      associated with fertility. Finally, SCH-0 and SCH-7 were associated with the odds
      for subclinical ketosis and metritis, respectively. In conclusion, SCH-0 but not
      SCH-7 is associated with reduced fertility in a herd of grazing dairy cows, but
      both were associated with health status.

PMID- 30219427
TI  - Implications of prolonged milking time on time budgets and lying behavior of cows
      in large pasture-based dairy herds.
AB  - In large Australian pasture-based dairy herds, it is common for the time taken to
      milk a herd of cows to be up to 4 h. Cows are collected from the paddock as a
      group, wait in turn in the dairy yard to be milked, and then return individually
      to the paddock or feed pad immediately after leaving the milking parlor. In such
      herds, we previously found a consistent milking order, resulting in some cows
      being regularly away from pasture for several hours per day more than others.
      Increased time away from pasture may affect the time budgets of cows because of
      decreased opportunity for grazing or lying down. Lying behavior is a high
      priority behavior for cows, and the duration of lying has been used as an
      important measure of their welfare. We applied activity monitors for 7 d to 15
      cows toward the beginning and 15 cows toward the end of the milking order in 10
      dairy herds milking 500 to 730 cows as a single group to understand the effect of
      extra time spent in the dairy on lying behavior. Study cows typically produced
      6,000 to 8,000 L in a 300-d lactation on rotary dairy platforms with 40 to 80
      units, being fed 2.5 to 6 kg of grain mix in the milking parlor daily, with the
      rest of the diet being supplied as pasture or forage provided in the pasture or
      close to the exit of the dairy. Over the 10 farms, 1,948 cow-days were available
      for analysis. The furthest paddocks on each farm were 1.8 to 3.5 km walking
      distance from the dairy. A wide range of steps were taken each day, ranging from
      1,705 to 15,075 (mean = 5,916). The main predictor of the number of steps was the
      farm on which the cows were located. Cows that spent less than an hour waiting to
      be milked (and would be unlikely to have their ability to lie down affected by
      the milking process) laid down for a mean of 9.8 h/d. Steps walked and delay in
      the dairy waiting to be milked were both significantly associated with lying
      time, but the effect was not large. A regression model accounting for the waiting
      time at the dairy, steps taken, cow age, and farm was used to investigate the
      relationship with daily lying time. For every 1,000 steps, lying time reduced by
      0.49 h; however, the number of steps explained only 1% of the variation in lying
      time. For every hour increase in waiting time at the dairy, lying decreased by
      approximately 14 min, but this explained only 14% of the variation in lying. We
      concluded that milking time durations of 2 to 4 h, common in large Australian
      pasture-based dairy herds, did not significantly affect the time budget for lying
      of individual cows in our study herds. Whereas the effect of long milking times
      does not appear to be a major risk to animal welfare in terms of lying time, the
      effect on cow health and production warrants further investigation.

PMID- 30219428
TI  - Technical note: Comparison of dry matter measurements from handheld near-infrared
      units with oven drying at 60 degrees C for 48 hours and other on-farm methods.
AB  - This study compared dry matter (DM) predictions of 3 handheld near-infrared
      spectrophotometer (NIRS) units (Moisture Tracker, Digi-Star Inc., Fort Atkinson,
      WI) to conventional oven drying at 60 degrees C using 2 alfalfa and 2 corn
      silages. In addition, on-farm DM methods [microwave, Koster tester (Koster
      Moisture Tester Inc., Brunswick, OH), and food dehydrator methods] were also
      compared. Corn and alfalfa silages (1,600 g) obtained from the University of
      Wisconsin Dairy Cattle Center (DCC) and the Arlington Research Station (ARS) were
      analyzed for DM daily for 20 d. Two NIRS calibration methods were also tested
      within each unit. The DM predicted from the factory-preset calibrations was NIRf.
      The adjusted DM prediction was NIRa, where the average difference between oven
      dried and NIRf determined on duplicate forage samples for 3 d before the
      experiment was used as a bias adjustment for all subsequent DM determinations.
      The average predicted DM from the 20 scans was recorded as the forage DM. The
      process was repeated 3 times with each NIRS unit. Two 100-g subsamples of each
      forage were also oven-dried for 48 h at 60 degrees C daily in a forced-air oven.
      Oven DM of ARS and DCC alfalfa silages were 37.3 +/- 1.1% and 48.5 +/- 1.9%,
      respectively (mean +/- standard deviation). Oven DM of ARS and DCC corn silages
      were 34.7 +/- 1.2% and 37.4 +/- 0.5%, respectively (mean +/- standard deviation).
      Dry matter determinations from NIRf were on average 3.5 units higher than the
      oven DM values. The NIRa DM predictions were on average 1.7 DM units lower than
      the oven DM values. Additionally, differences among the 3 NIRf probe results were
      detected (43.1, 40.7, and 41.3% DM, respectively), but all other results were
      similar between probes. Determinations of DM by the microwave and food dehydrator
      were also similar with the 60 degrees C, 48-h oven method, whereas the Koster
      tester was lower than the oven. The handheld NIRS units more accurately predicted
      DM content of the alfalfa silage but were not as accurate with corn silages when
      the factory preset calibrations were corrected for bias.

PMID- 30219429
TI  - Value of the Dutch Holstein Friesian germplasm collection to increase genetic
      variability and improve genetic merit.
AB  - National gene bank collections for Holstein Friesian (HF) dairy cattle were set
      up in the 1990s. In this study, we assessed the value of bulls from the Dutch HF
      germplasm collection, also known as cryobank bulls, to increase genetic
      variability and improve genetic merit in the current bull population (bulls born
      in 2010-2015). Genetic variability was defined as 1 minus the mean genomic
      similarity (SIMSNP) or as 1 minus the mean pedigree-based kinship (fPED). Genetic
      merit was defined as the mean estimated breeding value for the total merit index
      or for 1 of 3 subindices (yield, fertility, and udder health). Using optimal
      contribution selection, we minimized relatedness (maximized variability) or
      maximized genetic merit at restricted levels of relatedness. We compared breeding
      schemes with only bulls from 2010 to 2015 with schemes in which cryobank bulls
      were also included. When we minimized relatedness, inclusion of genotyped
      cryobank bulls decreased mean SIMSNP by 0.7% and inclusion of both genotyped and
      nongenotyped cryobank bulls decreased mean fPED by 2.6% (in absolute terms). When
      we maximized merit at restricted levels of relatedness, inclusion of cryobank
      bulls provided additional merit at any level of mean SIMSNP or mean fPED except
      for the total merit index at high levels of mean SIMSNP. Additional merit from
      cryobank bulls depended on (1) the relative emphasis on genetic variability and
      (2) the selection criterion. Additional merit was higher when more emphasis was
      put on genetic variability. For fertility, for example, it was 1.74 SD at a mean
      SIMSNP restriction of 64.5% and 0.37 SD at a mean SIMSNP restriction of 67.5%.
      Additional merit was low to nonexistent for the total merit index and higher for
      the subindices, especially for fertility. At a mean SIMSNP of 64.5%, for example,
      it was 0.60 SD for the total merit index and 1.74 SD for fertility. In
      conclusion, Dutch HF cryobank bulls can be used to increase genetic variability
      and improve genetic merit in the current population, although their value is very
      limited when selecting for the current total merit index. Anticipating changes in
      the breeding goal in the future, the germplasm collection is a valuable resource
      for commercial breeding populations.

PMID- 30219430
TI  - Effect of varying prepartum dietary cation-anion difference and calcium
      concentration on postpartum mineral and metabolite status and milk production of
      multiparous cows.
AB  - Eighty-two multiparous Holstein cows were enrolled 28 d before expected calving
      and assigned to 1 of 4 dietary treatments in a randomized block design experiment
      with a 2 * 2 factorial arrangement of treatments to determine the effect of
      feeding a neutral or acidogenic diet varying in Ca concentration on prepartum and
      postpartum intake, blood mineral and metabolite concentrations, and postpartum
      milk production. Prepartum diets were formulated to provide a dietary cation
      anion difference (DCAD) of -21 (negative, NEG) or -2 (neutral, NEU) mEq/100 g of
      dry matter with either 1.3% or 1.8% Ca. After calving, cows remained on trial
      through 63 d in milk (DIM) and were fed a common lactation diet. Urine pH was
      lower for NEG compared with NEU and tended to be lower for 1.8% Ca compared with
      1.3% Ca. Fractional excretion of Ca and Mg in urine was greater for NEG than for
      NEU. Prepartum plasma bicarbonate was lower and P was higher for NEG compared
      with NEU. Prepartum plasma P and blood urea nitrogen to creatinine ratio was
      higher for 1.3% compared with 1.8% Ca. Postpartum, concentrations of plasma total
      protein, albumin, blood urea nitrogen, Mg, and ionized Mg (iMg) were higher and
      Na was lower for NEU compared with NEG. An interaction of DCAD and Ca was
      observed for plasma creatinine, which was highest for cows fed NEU and 1.3% Ca
      compared with all other treatments. Interactions of DCAD and DIM were observed
      for plasma bicarbonate and iMg. Bicarbonate was higher at 3 DIM and lower at 14
      DIM for NEU compared with NEG. Concentrations of iMg were higher at 1, 2, and 14
      DIM for NEU compared with NEG. Interactions of Ca and DIM were observed for
      plasma Ca, Cl, and anion gap. Compared with cows fed 1.5% Ca, those fed 1.3% Ca
      had lower Ca and anion gap and higher Cl at 1 DIM and lower Cl and higher anion
      gap at 14 DIM. No differences were observed in body weight or body condition
      score due to DCAD or Ca. Prepartum dry matter intake (DMI) was lower for NEG
      compared with NEU and lower for 1.8% compared with 1.3% Ca. Postpartum DMI was
      not different among treatments. An interaction was observed for DCAD and DIM due
      to higher milk yield after 45 DIM for NEG compared with NEU. No differences were
      observed in milk component percentage or yield among treatments. There was an
      interaction of DIM and Ca for milk urea concentrations, which were higher at 5 wk
      and lower at 6 wk for 1.3% Ca compared with 1.8% Ca. These results suggest that
      feeding NEG prepartum alters plasma and urine mineral concentrations compared
      with feeding NEU and supports increased milk yield after 45 DIM. Feeding 1.8% Ca
      prepartum only improved plasma Ca at 1 DIM. Feeding either NEG or 1.8% Ca reduced
      DMI prepartum compared with NEU or 1.3% Ca.

PMID- 30219431
TI  - Barriers and facilitators affecting self-disclosure among male survivors of child
      sexual abuse: The service providers' perspective.
AB  - Research regarding child sexual abuse (CSA) indicates significant gender
      differences in disclosure rates, with males less likely to disclose their abuse
      compared to females. CSA can have lasting impact on a children's emotional,
      physical, and psychological wellbeing. While service providers play an
      instrumental role in providing care and support for male CSA survivors, little is
      known about their perceptions and experiences related to disclosure among these
      men. The aim of this qualitative study was to explore service providers'
      perceptions and awareness of disclosure-related barriers and facilitators amongst
      male CSA survivors. Individual interviews were conducted with eleven service
      providers. Study findings reveal four key themes related to the disclosure
      process among male CSA survivors: (a) personal characteristics, (b) interpersonal
      relations, (c) institutional elements, and (d) societal norms. Findings indicate
      that service providers understand and respond to complex challenges associated
      with disclosure of CSA among this marginalized population. Study findings
      demonstrate the need for additional research on the specific issues of gender
      bias and stigma associated with male sexual abuse. Along with their empirical
      significance, these findings can be used to develop more tailored public health
      and social service-related programming for male CSA survivors, their families,
      and the broader community to promote a safer and more supportive environment in
      which to discuss these sensitive and important issues. Recommendations to service
      providers are discussed.

PMID- 30219432
TI  - Effects of psyllium vs. placebo on constipation, weight, glycemia, and lipids: A
      randomized trial in patients with type 2 diabetes and chronic constipation.
AB  - OBJECTIVE: To compare the effects of baked psyllium supplementation versus those
      who received a placebo on constipation symptoms, body weight, glycemic and lipids
      control in patients with type 2 diabetes (T2D) and chronic constipation. METHODS:
      In a single-blinded, randomized controlled trial, 51 patients with T2D and
      chronic constipation with body mass index (BMI) 20-47 kg/m2 received either 10 g
      of psyllium pre-mixed in cookies twice per day or placebo cookies for 12 weeks.
      Constipation symptoms, body mass index (BMI), fasting plasma glucose (FPG),
      glycosylated hemoglobin (HbA1c), and lipid profile were determined at the
      beginning and end of 4, 8, and 12-week period. Constipation was evaluated with a
      stool diary (ROME III). RESULTS: The psyllium group showed improvement in
      constipation symptoms, body weight, glucose and lipid values compared with the
      baseline and the placebo group. Body weight and FPG decreased from baseline in
      the psyllium group (P < 0.001 and P = 0.056, respectively). The differences (95%
      CI) of absolute change of body weight (-2.0 (-3.0, -1.0) kg; P < 0.001), FPG (
      13.6 (-24.3, -2.9) mg/dl; P = .040), and HbA1c (-1.7 (-2.9, -0.5)); P = 0.002)
      between the groups were statistically significant. Cholesterol (-21.5 (-25.6, 
      14.4); P < 0.001), triglycerides (-20.0 (-32.3, -7.7); P = 0.021) and
      constipation symptoms (1.5 (0.4, 2.3); P < 0.001) decreased in the psyllium
      group. The compliance was good and no adverse effects were observed. CONCLUSION:
      In patients with T2D and chronic constipation, psyllium supplementation decreased
      constipation symptoms, body weight, glycemic, cholesterol, and increased HDLC
      levels.

PMID- 30219433
TI  - Spirulina platensis effectively ameliorates anthropometric measurements and
      obesity-related metabolic disorders in obese or overweight healthy individuals: A
      randomized controlled trial.
AB  - AIMS: Novel alternative treatments such as food supplements may be an effective
      approach to weight management. The aim of the present study was to investigate
      the possible effects of Spirulina Platensis (SP) on anthropometric measures,
      appetite and metabolic parameters in obese or overweight individuals. MATERIAL
      AND METHODS: A total of fifty-two obese and overweight subjects (25 kg/m2 <= body
      mass index (BMI) <40 kg/m2) were randomly selected to be allocated to SP (4 * 500
      mg daily tablets along with restricted calorie diet (RCD)) or placebo (placebo
      tablets along with RCD) for 12 weeks of intervention. Anthropometric measurements
      and appetite score were assessed at baseline, weeks 6 and 12. Biochemical
      assessments were performed at baseline and week 12. RESULTS: Thirty-eight
      participants completed the intervention. Body weight, waist circumference, body
      fat and BMI significantly reduced in the SP group compared to the placebo group
      (p < 0.001, p = 0.049, p = 0.049 and p = 0.02, respectively). In the SP group,
      the reduction triglycerides (TG) and high sensitivity C-reactive protein levels
      was considerably significant compared to the placebo group (p = 0.03, p = 0.02,
      respectively). Appetite score was significantly reduced in the SP group compared
      to the baseline (p < 0.001). CONCLUSIONS: This study suggests that spirulina
      platensis, as a complementary therapy may have beneficial effects on adherence to
      RCD, management of weight loss and also reduction in TG levels through possible
      modulatory effects on anti-inflammatory pathways.

PMID- 30219434
TI  - Effects of heated and thermoneutral yoga interventions on arterial stiffness in
      middle-aged adults.
AB  - The study investigated the efficacy of 12 weeks of heated and thermoneutral
      Bikram yoga in reducing arterial stiffness in middle-aged adults. Fifty-four
      sedentary adults (ages 40-60 years) completed 12 weeks of yoga at 40.5  degrees C
      (n = 21), yoga at 23  degrees C (n = 14) or time control (n = 19). Brachial-ankle
      pulse wave velocity (PWV) was not significantly altered by hot or thermoneutral
      yoga interventions.

PMID- 30219435
TI  - Capillary glycaemia responses to strength exercises performed before or after
      high-intensity interval exercise in Type 1 diabetes under real-life settings.
AB  - This study investigated the influence of performing strength exercises before or
      after high-intensity interval exercise on glycaemia during and postexercise in
      T1DM patients. Nine physically active adults with T1DM executed 30 min of
      strength exercises (SE) (3 sets at 10 RM) before 30 min of high-intensity
      interval exercise (HIIE) (10 * 60-s bout at ~90% HRmax interspersed with 60 s
      recovery) (SE + HIIE) or performed the reverse order (HIIE + SE) or rested in
      this period. Capillary glucose levels were measured each 15 min during and 60 min
      postexercise recovery. Significant lower glucose levels were observed in SE +
      HIIE at 60, 75 and 90 min, in comparison with REST. HIIE + SE lowered glycaemia
      at 30, 45 and 60 min compared with baseline concentrations, while SE + HIIE
      postponed this glucose decayment to 60 min, when compared with baseline levels.
      An increased glycaemia at 105 min compared with end-exercise levels were also
      observed in HIIE + SE. Carbohydrates ingested during exercise to correct
      hypoglycemia, insulin dosage at same day before and after protocols, and
      nocturnal hypoglycemia episodes were similar among the three conditions. It is
      concluded that the performance of HIIE before SE decreases glycaemia already at
      the end of first exercise modality, while the reverse order postpones it to the
      end of second exercise, although HIIE + SE improves glycemic stability throughout
      recovery. T1DM patients who tend to develop exercise-associated hypoglycemia may
      perform strength exercises before high-intensity interval exercise in a single
      session.

PMID- 30219437
TI  - On caring and sharing-Addressing psychological, biographical, and spiritual
      aspects in integrative cancer care: A qualitative interview study on physicians'
      perspectives.
AB  - BACKGROUND: Patients confronted with a cancer diagnosis experience a variety of
      existential needs encompassing emotional, psychological, and spiritual areas of
      being. A patient-centered care approach addressing such existential issues is
      recognized as an essential aspect of health care. The aim of this study is to
      explore what role psychological, biographical, and spiritual factors play for
      experienced doctors working in integrative cancer care. METHOD: The qualitative
      study was based on in-depth interviews with 35 purposively sampled doctors, all
      practicing integrative oncology in the field of anthroposophic medicine in
      hospitals and/or office-based practices in Germany and other countries. Data were
      analyzed using structured content analysis. RESULTS: Psychological, biographical,
      and spiritual factors are important issues in integrative cancer care. Prevailing
      themes identified in this study were enabling patients to participate in life,
      promoting autonomy and coping, stabilizing patients emotionally and cognitively,
      overcoming the disease, and-primarily if addressed by patients-integrating
      spiritual issues. Doctors offered conversation, counseling, and time, but also
      referred to art, music, literature, and nature, so that patients' ongoing
      emotional, psychological, and spiritual needs could be explored and addressed.
      Doctors' attitudes with regard to existential issues were seen as important, as
      was maintaining an attitude of openness towards existential issues. CONCLUSION:
      Doctors in integrative cancer care utilize different methods to explore the needs
      of patients and employ a variety of treatment methods that address not just
      patients' medical issues but their existential concerns as well.

PMID- 30219436
TI  - The improvement of oxidative stress by two proprietary herbal medicines in type 2
      diabetes.
AB  - OBJECTIVE: To evaluate the impact to oxidative stress, atherosclerosis and
      macrovascular disease by two proprietary herbal medicines including Ginkgo Leaf
      Tablets and Liuwei Dihuang Pills in type 2 diabetes. METHODS: The recruited 140
      type 2 diabetes were randomly divided into the treatment group and control group
      which were both received basic diabetic management including anti-hyperglycemia,
      anti-hypertension, life style adjustment and health education etc. Additionally,
      the treatment group was given both Ginkgo Leaf Tablets and Liuwei Dihuang Pills
      while the control group was given placebos of Ginkgo Leaf Tablets and Liuwei
      Dihuang Pills. The relative clinical indexes about macrovascular events
      occurrence, atherosclerosis degree(IMT levels), oxidative stress in vivo(plasma
      carboxymethyl lysine(CML) and 8-isoprostane(8-IsoP) levels), plasma glucose,
      plasma lipid, blood pressure, other drugs usage situations and so on of two
      groups before and after consecutive 36-month treatment were accurately collected
      and statistically analyzed. RESULTS: There were no significant differences of
      cardiovascular disease, cerebrovascular disease, IMT levels, plasma CML and 8
      IsoP levels between the two groups before treatment. After 36-month treatment,
      the plasma CML and 8-IsoP levels of treatment group were both significantly lower
      than control group (CML: 312.4 +/- 90.4 ng/ml versus 463.5 +/- 97.2 ng/ml, P <
      0.0001; 8-IsoP: 23.7 +/- 9.5 pg/ml versus 62.6 +/- 16.1 pg/ml, P < 0.0001)
      although this improvement was not shared with IMT and macrovascular events.
      CONCLUSION: Ginkgo Leaf Tablets and Liuwei Dihuang Pills are beneficial to
      oxidative stress which plays important role in diabetic atherosclerosis and
      macrovascular complications. The preventive and therapeutic values of herbal
      medicines will be proved in further diabetic complication researches.

PMID- 30219438
TI  - Development of a whole plant bioassay to test effects of potentized calcium
      carbonate in pillule formulation.
AB  - OBJECTIVES: From a pharmaceutical point of view, we see a need to develop stable
      preclinical test systems to identify and investigate effects of potentized
      remedies as used in Anthroposophic Medicine and Homeopathy. We evaluated a plant
      bioassay regarding its capacity to distinguish homeopathic remedies from placebo,
      applied as sucrose pillules. METHODS: Pea seed (Pisum sativum L) was soaked for
      24 hours in water with dissolved homeopathic or placebo pillules, or in water
      only. Shoot length was measured 14 days after planting and treatment groups were
      compared by analysis of variance (ANOVA). The stability of the system was
      validated by systematic negative control experiments. RESULTS: The system is
      suitable to test a common application form - sucrose pillules - of a potentized
      preparation without influence of the pharmaceutical carrier substance. A
      screening of 13 potentized preparations revealed Calcium carbonicum to affect pea
      shoot growth (p < 0.05). Three independent series of main experiments were
      performed with potentized Calcium carbonicum to assess reproducibility. Meta
      analysis of all data revealed significant effects of Calcium carbonicum 12c and
      30c on pea shoot growth (p < 0.05), which were however dependent on the date of
      experiment and/or the experimental series. CONCLUSIONS: Potentized Calcium
      carbonicum, applied as sucrose pillules, influenced pea shoot growth in the assay
      investigated. However, due to the small effect size and due to the modulation of
      the effects by still unknown external factors, further optimization of this
      bioassay is necessary to be used in pharmaceutical quality control or in
      investigating the biological or pharmaceutical mode of action of potentized
      preparations.

PMID- 30219439
TI  - Investigations on the constitutional types under consideration of anthropometric
      data, autonomic regulation and immunological parameters.
AB  - OBJECTIVES: Over time different systems were developed for the characterization
      of individuals according to their physical and psycho-vegetative traits which
      until today play a role in complementary medicine. This pilot study aimed at
      investigating if the concepts of polar constitutional types of anthroposophic
      medicine and according to Kretschmer can be further clarified using empirical
      method. METHODS: 96 participants, preselected by two polar body mass index (BMI)
      ranges (17-19.5 kg/m2 and 27-31 kg/m2), were categorized using both
      classification systems. Anthropometrical measurements were carried out and
      differences in the autonomic regulation were assessed using a questionnaire. From
      12 participants showing a pronounced polar constitutional type, production of
      reactive oxygen species, proliferation, autophagy, and glucose uptake by
      lymphocytes, monocytes and granulocytes were measured in vitro. RESULTS:
      Correlations between the BMI and the strength of constitutional classification
      were found for both classification systems. Additionally, a strong correlation
      between the two systems themselves could be seen. Analysis of the overall
      questionnaire score of autonomic regulation did not yield significant
      correlations. However, using a modified 11 item score, reliability (Cronbach
      alpha = 0.656) and a differentiation of polar constitutional types was
      demonstrated (p < 0.001). Regarding the immune function slightly varying levels
      of reactive oxygen species, autophagy in granulocytes and differences in the
      strength of inhibition of lymphocyte proliferation by dexamethasone and
      cyclosporine A were detected. However, most of these in vitro results did not
      reach significance. CONCLUSION: This study represents a first empirical approach
      toward the classification of anthroposophic constitutional types.

PMID- 30219440
TI  - An assessment of the scientific status of anthroposophic medicine, applying
      criteria from the philosophy of science.
AB  - OBJECTIVES: The objective was to evaluate the scientific status of anthroposophic
      medicine (AM) according to demarcation criteria proposed in contemporary
      philosophy of science. DESIGN: Criteria for what is science were retrieved from
      eight publications in the philosophy of science, focusing either on science in
      medicine or on the demarcation between science and pseudoscience or non-science.
      Criteria were combined, redundancies were excluded, and the final set of criteria
      was ordered in a logical sequence. The analysis yielded 11 demarcation criteria
      (community, domain, problems, goals, axiomatic basis, conceptual basis, quality
      of concepts, methodology, deontic basis, research products, tradition). RESULTS:
      Assessing the scientific status of AM according to the 11 criteria, all criteria
      were fulfilled by AM. DISCUSSION: AM is grounded on the notion that specific non
      atomistic holistic formative forces exist and can be empirically and rationally
      assessed. From a position claiming that such holistic forces cannot possibly
      exist or cannot be empirically and rationally assessed, the axiomatic and
      conceptual basis of AM can be contested. However, such an a priori rejection is
      problematic in the presence of empirical evidence supporting the validity of
      holistic concepts, as discussed in the paper. Future research should therefore
      focus on the tenability of the ontological reductionist position in science and
      on the further validation of AM non-atomistic holistic concepts, methods and
      practices. CONCLUSION: In this analysis, using criteria from philosophy of
      science, AM fulfilled all 11 criteria for what is science.

PMID- 30219441
TI  - Integrative cancer care in a certified Cancer Centre of a German Anthroposophic
      hospital.
AB  - OBJECTIVE: The concept of integrative oncology (IO) comprising guideline-oriented
      standard and add-on complementary medicine has gained growing importance. The
      Anthroposophic-integrative Cancer Centre (CC) at the hospital
      Gemeinschaftskrankenhaus (GKH) in Berlin has been implementing IO concepts during
      recent years. Furthermore, it is a certified CC and has been annually audited by
      national cancer authorities since 2012. The objective of the present study was to
      evaluate IO concepts of the certified CC GKH. METHODS: Clinical, demographic,
      integrative treatment and follow-up data were analyzed between 2011 and 2016. In
      addition, CC GKH quality measures were compared with those of nationwide
      benchmarking CCs. RESULTS: Between 2011 and 2016, 2.382 primary cancer patients,
      median age 66 years, were treated at the CC GKH. 70.1% of the patients showed
      either Union for International Cancer Control (UICC) stage 0, I, II or III and
      25.6% were in UICC stage IV. IO therapies included surgery (64.4% of patients),
      radiation (41.2%), and application of cytostatic drugs (53.9%), add-on mistletoe
      therapy (30.5%), and non-pharmacological interventions (87.3%). Regarding psycho
      oncological support and quota of patient's enrollment in studies the CC GKH
      performs above nationwide benchmarks. Research outcomes including safety issues,
      clinical impact as well as patient's health-related quality of life are
      continuously evaluated and integrated into hospital's decision-management.
      CONCLUSION: This analysis reveals that IO concepts are applied to a high
      proportion of male and female primary cancer patients of all age groups,
      indicating a successful implementation at the certified CC GKH. Ongoing clinical
      evaluations have been initiated and cost-effectiveness comparisons are under
      analyses.

PMID- 30219442
TI  - Taraxacum officinale extract shows antitumor effects on pediatric cancer cells
      and enhance mistletoe therapy.
AB  - OBJECTIVES: While Taraxacum officinale (dandelion) extracts showed antitumor
      effects on adult cancer cells, effects on pediatric tumor cells as a single agent
      or in combination with mistletoe extracts are hitherto unknown. MATERIAL AND
      METHODS: The anti-proliferative effects of an aqueous fermented Taraxacum
      officinale extract (Taraxacum) on a pediatric cancer cell line panel were
      assessed by cell viability assays (MTT). In two neuroblastoma cell lines, SH-SY5Y
      and Kelly, the effects on cell cycle distribution (PI staining), mitochondrial
      integrity (MitoTracker staining), invasion (Boyden chamber assay) and migration
      (Scratch-assay) as well as the synergistic effects of the co-treatment of
      Taraxacum and mistletoe preparations (Iscucin(r) Tiliae or Iscucin(r) Pini) were
      investigated. RESULTS: All tested cancer cell lines were more susceptible to
      Taraxacum than the normal human fibroblast cell line, NHDF-C. In neuroblastoma
      cell lines Taraxacum caused apoptosis and loss of mitochondrial integrity as well
      as an inhibition of invasion and migration. The simultaneous therapy of Taraxacum
      and the mistletoe extracts revealed synergistic effects. CONCLUSION: This
      preclinical data support the use of Taraxacum as a potential adjuvant application
      in pediatric oncology.

PMID- 30219443
TI  - Rosemary has immunosuppressant activity mediated through the STAT3 pathway.
AB  - OBJECTIVE: In Europe extracts of Rosmarinus officinalis were traditionally used
      for the treatment of rheumatic diseases. We investigated the capacity of
      standardized aqueous extracts of Rosmarinus officinalis on human primary
      lymphocyte function in vitro, as activated lymphocytes are an important mediator
      of rheumatic diseases. METHODS: Lymphocyte proliferation was measured using
      membrane-permeable dye carboxyfluorescein diacetate succinimidyl ester (CFSE).
      Apoptosis was analysed by surface staining of phosphatidylserine (annexin V
      assay) and necrosis was analysed by staining with propidium iodide. Modification
      of cell activity was detected by surface staining of CD69 and CD25. The activity
      of STAT3 in T-lymphocytes was determined by intracellular staining of STAT3
      molecules. All endpoints were analyzed by using flow cytometry. The Rosmarinus
      officinalis extract was investigated at concentrations of 0.05-25 mg/mL. Analysis
      of the extract was performed using HPLC methods. RESULTS: Rosmarinus officinalis
      inhibited proliferation of human lymphocytes and CD4+ T-cells in a dose-dependent
      manner (3.1-25 mg/mL) through induction of apoptosis. The intracellular
      signalling pathway STAT3 in T-cells, but not NF-kappaB and ERK1/2 in T- and B
      cells was inhibited in a dose-dependent manner by Rosmarinus officinalis (0.2-6.2
      mg/mL). Rosmanol, carnosolic acid, carnosol and trans-caffeic acid were tested in
      the same cellular models as the crude extract. From these, only trans-caffeic
      acid inhibited lymphocyte proliferation and STAT3 (30-100 MUg/mL). Trans-caffeic
      acid was found in the extract in a concentration of 14.7 MUg/mL. CONCLUSIONS: We
      conclude that an immunosuppressive effect of Rosmarinus officinalis is mostly due
      to the effect of trans-caffeic acid. It results in inhibition of the activity of
      STAT3 causing induction of apoptosis and inhibition of proliferation of T
      lymphocytes.

PMID- 30219444
TI  - Feeling the sound - short-term effect of a vibroacoustic music intervention on
      well-being and subjectively assessed warmth distribution in cancer patients-A
      randomized controlled trial.
AB  - OBJECTIVES: So far, the effects of vibroacoustic music therapy in cancer patients
      are unknown. However, used in anthroposophic medicine, it could be an approach to
      enhance well-being. The goal of this study was to evaluate the immediate effects
      of a sound-bed music intervention with respect to the subjective well-being as
      well as body warmth and pain. PATIENTS AND METHODS: We treated 48 cancer patients
      with 10 min of sound-bed intervention in a cross-over design. Primary outcome was
      the total sum of the Basler Mood Questionnaire (BMQ), secondary outcomes were
      subscales of the BMQ and questions addressing body warmth and pain. The EORTC-QLQ
      C30 was used as baseline assessment for quality of life (QOL). RESULTS: Patients
      had lower QOL values than the EORTC reference samples (p < .001, d = 0.90). The
      primary outcome increased after music (p < .001, d = 0.47), no changes were seen
      in the control condition (p = .73, d = 0.04), the time by condition interaction
      was significant (p < .05). SECONDARY OUTCOMES: Increase after music for the BMQ
      subscales inner balance (p < .001, d = 0.73), vitality (p < .001, d = 0.51) and
      vigilance (p < .001, d = 0.37) as well as for the additional questions
      satisfaction (p < .001, d = 0.43), current mood (p < .001, d = 0.43), body warmth
      (p < .05, d = 0.44) and warmth distribution (p < .01, d = 0.49). No significant
      changes were seen in pain levels and social extroversion. CONCLUSION: Sound-bed
      intervention improved momentary well-being and caused self-perceived
      physiological changes associated with relaxation beyond the benefits of simple
      resting time (control condition). Thus, it might be a promising approach to
      improve well-being in cancer patients.

PMID- 30219445
TI  - Acceptance, satisfaction and cost of an integrative anthroposophic program for
      pediatric respiratory diseases in a Swiss teaching hospital: An implementation
      report.
AB  - BACKGROUND: For the pilot phase of an integrative pediatric program, we defined
      inpatient treatment algorithms for bronchiolitis, asthma and pneumonia, using
      medications and nursing techniques from anthroposophic medicine (AM). Parents
      could choose AM treatment as add-on to conventional care. MATERIAL AND METHODS:
      To evaluate the 18-month pilot phase, parents of AM users were asked to complete
      the Client Satisfaction Questionnaire (CSQ-8) and a questionnaire on the AM
      treatment. Staff feedback was obtained through an open-ended questionnaire.
      Economic data for project set-up, medications and insurance reimbursements were
      collected. RESULTS: A total of 351 children with bronchiolitis, asthma and
      pneumonia were hospitalized. Of these, 137 children (39%) received AM treatment,
      with use increasing over time. 52 parents completed the questionnaire. Mean CSQ-8
      score was 29.77 (95% CI 29.04-30.5) which is high in literature comparison. 96%
      of parents were mostly or very satisfied with AM; 96% considered AM as somewhat
      or very helpful for their child; 94% considered they learnt skills to better care
      for their child. The staff questionnaire revealed positive points about enlarged
      care offer, closer contact with the child, more relaxed children and greater role
      for parents; weak points included insufficient knowledge of AM and additional
      nursing time needed. Cost for staff training and medications were nearly
      compensated by AM related insurance reimbursements. CONCLUSIONS: Introduction of
      anthroposophic treatments were well-accepted and led to high parent satisfaction.
      Additional insurance reimbursements outweighed costs. The program has now been
      expanded into a center for integrative pediatrics.

PMID- 30219446
TI  - Anthroposophic medicine in the treatment of pediatric pseudocroup: A systematic
      review.
AB  - BACKGROUND: In Europe only few integrative pediatric wards exists and there are
      two German hospitals focusing on anthroposophic medicine as part of complementary
      and alternative medicine (CAM). Whilst the most common pediatric diseases are
      treated here, pseudocroup patients make up a large group in these hospitals,
      receiving conventional as well as anthroposophic therapies. However,
      effectiveness of these therapy concepts mostly based on physicians' experiences
      but clinical studies are hitherto missing. METHODS: A systematic literature
      search identifying therapy approaches for pseudocroup in children was conducted
      in general electronic databases (Cochrane Library, PubMed, OVID) and in CAM
      specific databases (CAMbase, CAM-QUEST(r), Anthromedics). Search results were
      screened for anthroposophic therapy options. In addition, anthroposophic
      guidebooks were handsearched for relevant information. RESULTS: Among 157
      articles fulfilling search criteria one retrospective study, and five experience
      reports describing anthroposophic treatments were identified. Several medications
      for the treatment of pseudocroup were mentioned such as Aconitum, Apis, Bryonia,
      Hepar sulfuris, Lavender, Pyrit, Sambucus and Spongia. During appropriate use no
      adverse effects were reported. CONCLUSION: Anthroposophic medicine harbors a
      broad spectrum of remedies for the treatment of pseudocroup in children. In
      particular, Aconitum, Bryonia and Spongia are frequently recommended; however,
      clinical trials investigating the effectiveness are sparse. Therefore,
      development and validation of therapy strategies are required.

PMID- 30219447
TI  - Effect of topical rosemary essential oil on Raynaud phenomenon in systemic
      sclerosis.
AB  - INTRODUCTION: Raynaud's phenomenon is the earliest manifestation of systemic
      sclerosis. Nitroglycerin gel is the only proven topical therapy. METHODS: A 53
      year-old woman with systemic sclerosis had topical Rosamarinus officinalis
      (rosemary) oil, often used in anthroposophic medicine, applied to her hands over
      3days and then, separately, olive oil. RESULTS: Thermography images showed
      significant warming of fingers after rosemary oil, but not after olive oil,
      coinciding with the patient's subjective experience. CONCLUSIONS: Topical
      Rosamarinus officinalis oil had a vasodilator and warming effect in a patient
      with systemic sclerosis and Raynaud's phenomenon.

PMID- 30219448
TI  - A collaborative model of integrative care: Synergy between Anthroposophic music
      therapy, acupuncture, and spiritual care in two patients with breast cancer.
AB  - Complementary/integrative medicine (CIM) has been shown to play an important role
      in supportive cancer care, relieving symptoms and improving quality of life among
      oncology patients. Communication between CIM practitioners and oncology
      healthcare professionals has been researched in depth, while little attention has
      been paid to the interaction between CIM practitioners from different disciplines
      who work together in the integrative oncology setting. The present paper explores
      the interaction between an Anthroposophic music therapist and a spiritual care
      provider who co-treated two female patients with breast cancer undergoing
      chemotherapy. The joint CIM treatments took place in an Integrative Oncology
      service in northern Israel, and the collaboration between the two practitioners
      resulted in a synergistic therapeutic process, promoting the patients' wellbeing
      and facilitating spiritual growth. There is a need to further explore therapeutic
      interactions between CIM therapists from different disciplines, who often work
      together in the integrative oncology setting. Collaboration between different CIM
      disciplines can lead to a synergy which goes beyond an additive effect of the
      individual therapies.

PMID- 30219449
TI  - Safety of high-dose intravenous mistletoe therapy in pediatric cancer patients: A
      case series.
AB  - BACKGROUND: Long-term survival of children with cancer has reached rates of up to
      80%. Nevertheless, continued research devoted to further improvement of survival
      rates especially for patients with high-risk illnesses is necessary. Recent
      studies have shown direct positive effects on tumor reduction through Viscum
      album (mistletoe) extracts in adults, mainly as a result of higher dosage
      treatment and intravenous or intratumoral application. PATIENTS AND METHOD: A
      retrospective analysis of data was carried out of all oncological, pediatric
      patients treated with intravenous high-dose mistletoe therapy for a period of two
      years (11/2013-11/2015). RESULTS: A total of ten non-coherent cases were
      examined, all suffering from advanced and/or relapsed forms of cancer (leukemia,
      neuroblastoma, nephroblastoma, osteosarcoma, lymphoma, anaplastic astrocytoma,
      atypical teratoid rhabdoid tumor and soft tissue sarcoma). Patients were treated
      for an average period of 48 days with a mean survival rate of 130 days after
      beginning the mistletoe therapy. Partial remission was observed in four and a
      slowed disease progression was monitored in two patients. However, unrestricted
      progression of disease was documented in two other patients. Patients showed side
      effects including fever as well as fatigue and in some cases systemic
      inflammatory reactions with transient organ impairment occurred. CONCLUSION: Our
      study underpinned the safety and feasibility of high-dose mistletoe infusion in
      children with advanced stages of cancer and showed noteworthy antineoplastic
      effects, which should be verified in a prospective clinical phase II/III-study.
      Because of possible side effects, the treatment should be implemented only in an
      in-patient setting in experienced pediatric oncology centers.

PMID- 30219450
TI  - Reduction of the frequency of recurrent diverticulitis episodes under treatment
      with the integrative medicine therapies Carpellum Mali comp. and Kalium aceticum
      comp.-A case report.
AB  - BACKGROUND: Colonic diverticula develop in at least 60% of elderly patients. Less
      than 25% of these develop diverticulitis. Recurrent episodes are experienced by
      about 13% of the symptomatic patients. The effect on prevention of recurrent
      diverticulitis of currently used therapies is controversial. Surgical colon
      resection is used in some patients in emergency or to prevent future episodes and
      complications. Carpellum Mali comp. (Juglans regia, Testa; Pirus malus,
      Carpellum) and Kalium aceticum comp. (Kalium carbonicum, Acetum vini destillatum,
      Antimonit, Crocus sativus, Spiritus e vino, Corallium rubrum) - preparations of
      Integrative Anthroposophic Medicine - have been used for at least 60 years to
      improve chronic abdominal pain and to treat obstipation, irritable bowel syndrome
      and colitis. CASE PRESENTATION: A 72-year-old retired physician presented in 2013
      with a 7-year history of recurrent diverticulitis. During the first 6 years,
      three to four episodes each year required antibiotic therapy. In 2013 the
      episodes became more frequent, occurring approximately every 2 months. The
      patient was concerned about risks from repeated antibiotic treatment and the
      potential need for surgery. Oral Carpellum Mali comp. and subcutaneous Kalium
      aceticum comp. treatments were added to the therapy in March. The patient
      experienced improvement over 4 months without any symptoms. In the following 28
      months she had 4 minor diverticulitis episodes, followed by 11-months without any
      flares; she reported no side effects in the 41-month follow-up period.
      CONCLUSION: Carpellum Mali comp. and Kalium aceticum comp. seem to have been
      helpful in the case presented here. Experiences with theses remedies in recurrent
      diverticulitis should be collected to determine whether it would be meaningful to
      carry out further investigations.

PMID- 30219451
TI  - Osteopathic care for low back pain and neck pain: A cost-utility analysis.
AB  - OBJECTIVES: The aim was to examine the health and economic consequences of
      osteopathic care for low back pain and neck pain in addition to usual care
      compared to usual care alone. DESIGN: A decision tree model considering a one
      year time horizon was applied. The analysis occurred from a health insurance
      perspective only considering direct medical costs. The health effects were
      expressed as quality-adjusted life years (QALYs). MAIN OUTCOMES: The main outcome
      was the incremental cost-effectiveness ratio (ICER). The uncertainty around key
      input parameters was addressed applying one-way and probabilistic sensitivity
      analyses (5000 simulations). RESULTS: For low back pain, osteopathy resulted in
      cost savings (?385.1 vs ?501.8/patient) at improved QALYs (0.666 vs. 0.614)
      compared to usual care. For neck pain, osteopathy resulted in additional costs
      (?577.3 vs. ?521.0) and improved QALYs (0.639 vs. 0.609) resulting in an ICER of
      ?1,870/QALY. The one-way sensitivity analysis identified the hospitalization cost
      (back) and osteopathy cost (neck) as major cost drivers. The probabilistic
      sensitivity analysis resulted in an average net saving of ?163 (95%CI-?260, 
      ?49.1) and a QALY gain of 0.06 (95%CI -0.06, 0.17) for low back pain and an
      average additional cost of ?55.1 (95%CI ?20.9, ?129) and improved QALY gain of
      0.03 (95%CI-0.06, 0.12) for neck pain. CONCLUSIONS: Osteopathy was found to be a
      'dominant' (low back pain) and cost-effective strategy (neck pain) compared to
      usual care. Further health economic evaluation studies considering a broader
      range of cost items and longer time horizon are required.

PMID- 30219452
TI  - Mind-body therapies: Connecting the parts and embracing diversity.

PMID- 30219453
TI  - "Yoga resets my inner peace barometer": A qualitative study illuminating the
      pathways of how yoga impacts one's relationship to oneself and to others.
AB  - OBJECTIVES: The purpose of this qualitative study was twofold: (1) to better
      understand how yoga practitioners perceive intra- and interpersonal outcomes of
      their yoga practice, and (2) to develop a conceptual model of yoga effects on
      intra- and interpersonal outcomes that may underlie the "relational" influences
      of yoga. DESIGN: As part of a larger study, 107 community-dwelling yoga
      practitioners (age M=41.2+/-15.9years) completed open-ended questions which asked
      questions focusing on whether yoga influences one's relationship to oneself and
      to others. A subsample (n=12) completed in-depth interviews. The open-ended
      responses were analyzed using content analysis, and verbatim interview
      transcripts were analyzed for emergent themes using a constant comparison
      approach. RESULTS: Four emerging themes were identified such that practitioners
      talked about the ability of yoga to generate calm states, mindfulness, (self
      )compassion, and a sense of connectedness. Throughout the themes, a common
      pattern emerged such that yoga practice first led to positive intrapersonal
      changes, which then influenced one's interpersonal relationships. Based on these
      results, a conceptual model was developed depicting potential pathways of how
      yoga works to enhance relational outcomes. CONCLUSION: Findings demonstrate the
      promise yoga holds to improve one's relationship to oneself (intrapersonal)
      through mindfulness and self-compassion, and to others (interpersonal), through
      the enhancement of compassion and social connectedness, which may potentially
      lead to enhanced health and wellbeing outcomes. Further empirical testing of the
      model is warranted.

PMID- 30219454
TI  - Exploring the efficacy and safety of topical Jaungo application in patients with
      atopic dermatitis: A pilot randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease
      with an increasing prevalence. In Korea, Jaungo is a traditional medicinal
      ointment, which is commonly used for treating skin wounds. OBJECTIVE: Thus, we
      aim to explore the basic clinical efficacy and safety data for Jaungo in patients
      with AD. METHODS: This study was a pilot randomized, double-blind, placebo
      controlled, single-center trial with three groups. The participants in treatment
      group 1 applied Jaungo to the lesion twice a day for 3 weeks. Those in treatment
      group 2 applied Jaungo and placebo ointments to the lesion once a day for 3
      weeks. Those in the placebo group applied placebo ointments to the lesion twice a
      day for 3 weeks. The Eczema Area and Severity Index and SCORing Atopic Dermatitis
      scores, transepidermal water loss value, and Dermatology Life Quality Index score
      were assessed. The outcomes used to evaluate safety were the Draize score, blood
      test results, and expert opinion. RESULTS: In total, 28 patients (82.4%)
      completed the study. During the study, significant decline of EASI scores in
      treatment group 2 and placebo group was observed (p < 0.05). And there was
      significant decline of SCORAD scores in treatment group1 and placebo group (p <
      0.05). Patients in all groups showed decreased TEWL and DLQI scores with no
      significant difference. There was significant decline of IL-17 in all groups (p <
      0.05). No serious adverse event was observed. CONCLUSION: This is the first study
      that has explored the potential therapeutic effect of Jaungo as a complementary
      therapy for AD. However, further large study with adjusting placebo ingredients
      is needed to confirm the effectiveness of Jaungo in patients with chronic-phase
      AD.

PMID- 30219455
TI  - Yoga therapy for military personnel and veterans: Qualitative perspectives of
      yoga students and instructors.
AB  - OBJECTIVE: Millions of military personnel and veterans live with chronic mental
      and physical health conditions that often do not respond well to pharmacological
      treatments. Serious side effects and lack of treatment response have led to
      widespread efforts to study and promote non-pharmacological and behavioral health
      treatments for many chronic health conditions. Yoga is an increasingly popular
      mind-body intervention that has growing research support for its efficacy and
      safety. Our objective was to explore the attitudes, perspectives, and preferences
      of military personnel and veterans toward yoga as a therapeutic modality, thus
      providing needed information for designing and promoting yoga interventions for
      this population. METHODS: Participants included 24 individuals with yoga
      experience and current or past military service and 12 instructors who have
      taught yoga for military personnel and/or veterans. A semi-structured set of
      questions guided interviews with each participant. RESULTS: Five themes emerged
      from the interviews: (1) mental health benefits experienced from yoga practice;
      (2) physical health benefits experienced from yoga practice; (3) important yoga
      elements and conditions that support effective practice; (4) facilitators for
      engaging military in yoga practice; and (5) challenges and barriers to yoga
      practice for military. CONCLUSIONS: The study highlights consistent reports of
      mental and physical benefits of yoga practice, ongoing stigma resulting in the
      need for combatting and demystifying yoga and other complementary and integrative
      health (CIH) practices, the importance of designing interventions to address the
      unique mental health issues and perspectives of this population, and the
      importance of efforts by military leadership to bring CIH to military personnel
      and veterans. Rigorous research addressing these findings, along with further
      research on the efficacy and effectiveness of yoga interventions for treating
      various conditions are needed.

PMID- 30219456
TI  - "Maybe black girls do yoga": A focus group study with predominantly low-income
      African-American women.
AB  - OBJECTIVE: To explore African American (AA) women's use of mind-body therapies,
      such as yoga and mindfulness, and factors that impact their experiences,
      observations and opinions. DESIGN: Focus groups were conducted to better
      understand how AA women perceive mind-body therapies and how to best bring these
      interventions into their community. Interviews were audiotaped and transcribed.
      SETTING: The urban Midwest. OUTCOME MEASURES: In addition to qualitative
      outcomes, descriptive measures included the Perceived Stressor Scale, Beliefs
      About Yoga Scale, and Determinants of Meditation Practice Inventory (DOMPI).
      RESULTS: Twenty-two, predominantly low-income (75% reported income <$50,000) and
      single (82%) women participated in three age stratified focus groups (18-34
      years, 35-65 years, 66 years and older). Participants acknowledged life stress
      and shared common coping mechanisms. They recognized that yoga and mindfulness
      could be beneficial and discussed barriers to practice (including personal and
      structural). Younger women reported more time constraints as barriers, middle
      aged women had more experience with yoga, and older women identified the
      spiritual component to yoga/mindfulness as potentially conflicting with current
      coping strategies. Participants suggested ways to share mind-body therapies
      within the AA community along with solutions for engagement. CONCLUSIONS: AA
      women acknowledged stress in their lives and recognized the need for additional
      coping measures. Although women reported interest in yoga/mindfulness they
      identified barriers, including limited access to convenient classes, and offered
      suggestions for bringing yoga and mindfulness to their communities.

PMID- 30219457
TI  - Yoga therapy: Efficacy, mechanisms and implementation.

PMID- 30219458
TI  - Effect of yoga on chronic non-specific neck pain: An unconditional growth model.
AB  - OBJECTIVE: Chronic neck pain is a common problem that affects approximately half
      of the population. Conventional treatments such as medication and exercise have
      shown limited analgesic effects. This analysis is based on an original study that
      was conducted to investigate the physical and behavioral effects of a 9-week
      Iyengar yoga course on chronic non-specific neck pain. This secondary analysis
      uses linear mixed models to investigate the individual trajectories of pain
      intensity in participants before, during and after the Iyengar yoga course.
      METHOD: Participants with chronic non-specific neck pain were selected for the
      study. The participants suffered from neck pain for at least 5 days per week for
      at least the preceding 3 months, with a mean neck pain intensity (NPI) of 40 mm
      or more on a Visual Analog Scale of 100 mm. The participants were randomized to
      either a yoga group (23) or to a self-directed exercise group (24). The mean age
      of the participants in the yoga group was 46, and ranged from 19 to 59. The
      participants in the yoga group participated in an Iyengar yoga program designed
      to treat chronic non-specific neck pain. Our current analysis only includes
      participants who were initially randomized into the yoga group. The average
      weekly neck pain intensity at baseline, during and post intervention, comprising
      11 total time points, was used to construct the growth models. We performed a
      step-up linear mixed model analysis to investigate change in NPI during the yoga
      intervention. We fit nested models using restricted maximum-likelihood estimation
      (REML), tested fixed effects with Wald test p-values and random effects with the
      likelihood ratio test. We constructed 10 REML models. RESULTS: The model that fit
      the data best was an unconditional random quadratic growth model, with a first
      order auto-regressive structure specified for the residual R matrix. Participants
      in the yoga group showed significant variation in NPI. They demonstrated
      variation in their intercepts, in their linear rates of change, and most
      tellingly, in their quadratic rates of change. CONCLUSIONS: While all
      participants benefitted from the yoga intervention, the degree to which they
      benefitted varied. Additionally, they did not experience a consistent rate of
      reduction in NPI - their NPI fluctuated, either increasing and then decreasing,
      or vice-versa. We comment on the clinical and research implications of our
      findings.

PMID- 30219460
TI  - "Dance Therapy" as a psychotherapeutic movement intervention in Parkinson's
      disease.
AB  - BACKGROUND: Previous studies in Parkinson's Disease (PD) have described benefits
      of dance for motor and non-motor outcomes, yet few studies specifically look at
      Dance Therapy (DT) as a specific psychotherapeutic model for PD. DT is the
      psychotherapeutic use of movement to improve physical, emotional, cognitive, and
      social integration and wellbeing. OBJECTIVE: 1) Explore the safety and
      feasibility of a 10-week DT program for PD. 2) Collect pilot data on efficacy of
      DT. DESIGN/METHODS: Prospective, randomized-controlled study in subjects with PD.
      13 participants randomized 2:1 to DT (n = 9) or support group (n = 4).
      Assessments were completed 1-2 weeks prior to the first session and after the
      final session, and included attendance, Hoehn and Yahr Scale (H&Y), Unified
      Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment,
      Timed Up and Go, Berg Balance Scale, Beck Depression Inventory, Fatigue Severity
      Scale, Visual Analog Fatigue Scale, Parkinson's Disease Questionnaire-39, and an
      exit satisfaction survey. RESULTS: All participants completed the study. The
      control group was older and had a higher mean baseline MDS-UPDRS III score (27.56
      dance vs. 40.75 control) and H&Y score (2.11 dance vs. 2.50 control). 7 of 9 in
      DT and all control subjects attended at least 70% of classes. All participants in
      DT enjoyed the classes and most felt they were beneficial. The greatest
      improvement in motor measures was in MDS-UPDRS III (-4.12 (dance) vs. -1.75
      (control)). Non-motor outcomes were explored as well. CONCLUSIONS: DT is
      introduced as an enjoyable mind-body intervention for PD. Further studies powered
      for efficacy and with groups matched for disease severity are warranted.

PMID- 30219459
TI  - Effects of sunlight exposure and vitamin D supplementation on vitamin D levels in
      postmenopausal women in rural Thailand: A randomized controlled trial.
AB  - BACKGROUND: Despite the abundant sunlight in Thailand, vitamin D deficiency is
      common in premenopausal and postmenopausal Thai women. Sunlight exposure is a
      natural way to increase one's intake of vitamin D. However, limited research has
      been conducted regarding natural exposure to sunlight as a strategy to improve
      vitamin D status in postmenopausal women. OBJECTIVE: This study aimed to
      determine the effects of sunlight exposure compared with oral supplementation
      with vitamin D2 (weekly 20,000 IU) in combination with sunlight exposure on
      25(OH)D levels. METHODS: A 12-week randomized controlled trial was conducted in
      52 postmenopausal women, age 50-70 years. The participants were randomized to
      either the sunlight exposure group or the sunlight exposure with vitamin D
      supplementation group. Serum 25(OH)D concentration and parathyroid hormone (PTH)
      were measured using standard assays at baseline and 12 weeks. RESULTS: After 12
      weeks, mean serum 25(OH)D had decreased from 32.3 to 29.7 ng/ml in the sunlight
      exposure group, but significantly increased in the combination group (from 29.9
      to 32.4 ng/ml). At the end of the study, 25(OH)D levels were significantly higher
      in the sunlight exposure with vitamin D supplementation group compared with the
      sunlight exposure group. However, this difference was not observed in women aged
      >60 years. Serum PTH had decreased in both groups, but not to a significant
      extent. CONCLUSION: A combination of weekly vitamin D2 supplementation at a dose
      of 20,000 IU with sunlight exposure is more effective than sunlight exposure
      alone in postmenopausal Thai women. Sunlight exposure alone is not sufficient to
      maintain 25-hydroxyvitamin D levels in this setting.

PMID- 30219461
TI  - Misinterpretation of results in a randomized controlled clinical trial that
      evaluate quality of life when using a simple acupressure protocol in women with
      primary dysmenorrhea.

PMID- 30219462
TI  - Commentary on "Tango for treatment of motor and non-motor manifestations in
      Parkinson's disease: A randomized control study" by Romenets et al., 2015.

PMID- 30219463
TI  - In Reply to the Letter to the Editor Regarding "A randomized controlled clinical
      trial evaluating quality of life when using a simple acupressure protocol in
      women with primary dysmenorrhea".

PMID- 30219464
TI  - Answer to a Commentary on "Tango for treatment of motor and non-motor
      manifestations in Parkinson's disease: A randomized control study".

PMID- 30219465
TI  - Conventional treatment integrated with Chinese herbal medicine improves the
      survival rate of patients with advanced non-small cell lung cancer.
AB  - OBJECTIVES: The main objective of this study was to assess whether treatment with
      epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined
      with Chinese herbal medicine (CHM), can improve the five-year survival rate in
      patients suffering from advanced non-small cell lung cancer (NSCLC), compared to
      patients treated by EGFR-TKIs alone. INTERVENTIONS AND MAIN OUTCOME MEASURES: The
      study is based on information in the sub-dataset of the National Health Insurance
      Research Database (NHIRD) from years 2000 to 2010, during which time a total of
      14,244 patients were diagnosed with NSCLC in Taiwan. After selection by exclusion
      criteria and matching process, 2,616 NSCLC patients were included in the study.
      Statistical analysis was utilized to evaluate the differences in characteristic
      distribution, and to compare the survival rates between the CHM cohort and non
      CHM cohort. RESULTS: Patients with advanced NSCLC using CHM as an adjunct therapy
      exhibited a significantly improved survival rate [hazard ration (HR) = 0.8; 95%
      confidence interval (CI): 0.73-0.87, p value<0.001], compared with non-CHM users.
      Based on a survival analysis by Kaplan-Meier method, the 5-year survival rate of
      CHM users was 4.9% higher, with the most notable difference being an elevated 2
      year survival rate of up to 12.75%. In addition to the survival rate analysis, we
      provide the ten most used single herbs and herbal formulas prescribed for
      patients with advanced NSCLC. CONCLUSIONS: This nationwide retrospective cohort
      study provides evidence supporting CHM as an effective adjunctive therapy to
      ameliorate the side effects of target therapy and prolong the five-year survival
      rate of patients with advanced NSCLC.

PMID- 30219466
TI  - The effects of guided imagery on state and trait anxiety and sleep quality among
      patients receiving hemodialysis: A randomized controlled trial.
AB  - OBJECTIVE: This study aimed to investigate the effects ofguided imagery on state
      and trait anxiety and sleep quality among hemodial ysis patients. DESIGN: This
      was a randomized controlled trial. A total of seventy hemodialysis patients were
      assigned through block randomization to either an intervention group to receive
      guided imagery or a control group to receive routine care services. SETTING: The
      study was performed in the hemodialysis unit of Akhavan teaching hospital,
      Kashan, Iran. INTERVENTION: In addition to routine care services, patients in the
      intervention group received guided imagery six times a week for four successive
      weeks via listening to a guided imagery instructional compact disk and following
      the instructions. PRIMARY OUTCOMES: Before and four weeks after the intervention,
      state and trait anxiety and sleep quality were measured via Spielberger's State
      Trait Anxiety Inventory and Pittsburgh Sleep Quality Index. RESULTS: The results
      of analysis of covariance showed that the intervention and the control groups
      significantly differed from each other respecting the posttest mean scores of
      state anxiety (adjusted mean difference: -9.11; 95% CI = -10.26 to_-7.96; P <
      0.001), trait anxiety (adjusted mean difference: -8.94; 95% CI = -10.31_to -7.57;
      P < 0.001), and sleep quality (adjusted mean difference: -0.877; 95% CI = 
      1.51_to -0.24; P < 0.007). CONCLUSIONS: Guided imagery can significantly
      alleviate anxiety and improve sleep quality among hemodialysis patients. Nurses
      are recommended to use guided imagery to alleviate hemodialysis patients' anxiety
      and improve their sleep quality.

PMID- 30219467
TI  - Safety and psychological impact of sailing adventure therapy among Veterans with
      substance use disorders.
AB  - OBJECTIVES: Many Veterans suffer from substance use disorders (SUDs). Treatment
      challenges include poor treatment engagement and high relapse rates.
      Complementary interventions have the potential to enhance both. This study was a
      preliminary evaluation of sailing adventure therapy (SAT) for this population.
      DESIGN: Retrospective chart review. Participants in the intervention were 22
      Veterans (20 male, 2 female) aged 22-65 who entered a Veterans Administration
      residential SUD treatment program. All subjects had two or more SUDs, and many
      had psychiatric (95%) and/or medical (77%) comorbidities. The age, gender and
      diagnosis-matched control group (n = 22) received residential SUD treatment as
      usual (TAU) in the same program but without SAT. SETTING: Residential SUD
      treatment program at a Veterans Administration Medical Center. INTERVENTION:
      Sailing adventure therapy. MAIN OUTCOME MEASURES: Positive and Negative Affect
      Schedule (PANAS), State Trait Anxiety Inventory six-item short form (STAI: Y-6
      item), Acceptance and Action Questionnaire II (AAQ II), Five Facet Mindfulness
      Questionnaire (FFMQ) and a locally developed patient survey. Outcome comparison
      among SAT plus TAU group versus TAU - only group included measures of successful
      completion of residential SUD treatment program as well as psychiatric
      hospitalizations and/or residential SUD treatment program readmissions within 12
      months. RESULTS: Neither physical injuries nor increases in anxiety or negative
      affect occurred, as measured by the PANAS (positive change, p = 0.351; negative
      change, p = 0.605) and the STAI: Y-6 item (p = 0.144) respectively. There was no
      significant change in FFMQ (p = 0.580) but a significant increase occurred in AAQ
      II scores (p = 0.036) indicating an increase in psychological flexibility. Survey
      responses indicated the participants perceived the experience to be both
      pleasurable and calming. The preliminary outcome evaluation revealed a
      significant between-group difference (X2 = 5.34, DF = 1, p = 0.02, r = 0.35)
      indicating participating in SAT was associated with a greater likelihood of
      successfully completing residential SUD treatment. However, there were no
      significant between-group differences in number of psychiatric hospitalizations
      (X2 = 1.09, DF = 1, p = 0.29, r = 0.16) or residential substance abuse treatment
      program readmissions (X2 = 0.23, DF = 1, p = 0.64, r = 0.07) in the 12 months
      after discharge from the program. CONCLUSIONS: Preliminary evidence suggests that
      SAT is physically safe and not associated with increased anxiety or negative
      affect. Participant's perceptions of the experience were positive. Preliminary
      outcome measures suggest associations between participation in SAT and increased
      psychological flexibility as well as successful completion of a residential SUD
      treatment program. Further research is indicated to determine whether SAT may be
      developed as an effective complementary intervention for Veterans with SUDs.

PMID- 30219468
TI  - Differences between vegetarian and omnivorous yoga practitioners-Results of a
      nationally representative survey of US adult yoga practitioners.
AB  - BACKGROUND: To examine the prevalence of vegetarianism among yoga practitioners,
      and to explore differences and similarities between yoga practitioners who also
      use vegetarian diet and those who do not. DESIGN AND SETTING: Using cross
      sectional data from the 2012 National Health Interview Survey (NHIS) (N =
      34,525), weighted frequencies for 12-month prevalence of vegetarian diet use
      among yoga practitioners were analyzed. Logistic regression analyses were used to
      analyze sociodemographic and clinical predictors of vegetarian diet use. RESULTS:
      A total of 1.7 million US yoga practitioners have used a vegetarian diet in the
      past 12 months (8.3%), compared to 2.7 million non-yoga practitioners (1.3%).
      Yoga practitioners who were aged between 30 and 64 years as compared to being 29
      years or younger were more likely to have used a vegetarian diet in the past 12
      months; while those being in a relationship (OR = 0.64), overweight (OR = 0.54),
      smoking (OR 0.64) or having private health insurance (OR = 0.59) were less
      likely. Vegetarian diet practitioners more often included meditation as part of
      their yoga practice and more often chose yoga because it had a holistic focus,
      and was perceived to treat the cause and not the symptoms of their health
      complaint. CONCLUSIONS: Yoga practitioners following a vegetarian diet seem to
      embrace yoga more as a lifestyle than as a therapy.

PMID- 30219469
TI  - Trauma-informed yoga training in Kenya: A qualitative pilot study on feasibility
      and acceptability.
AB  - The current study presents a pilot qualitative exploration of the collaboration
      of two yoga service agencies in implementing a trauma-informed mindfulness-based
      teaching curriculum in Kenya, Africa. Yoga and mindfulness practices have been
      demonstrated as successful complementary and alternative approaches to managing
      the impacts of stress trauma. This study explores the feasibility and
      acceptability of mindfulness programming for yoga teachers in the Nairobi region
      of Kenya. Grounded theory is used to explore survey results. Outcomes demonstrate
      promise for both acceptability and feasibility. Curriculum tools were viewed as
      effective, and participants indicated intention to both utilize and share tools.
      Reflections on program effectiveness and impacts are addressed, as are potential
      considerations for improved program translation. Findings suggest the potential
      benefit for future collaborations, and also suggest best practices considerations
      for global implementation of embodied mindfulness programming.

PMID- 30219470
TI  - Neuromuscular efficiency of the multifidus muscle in pilates practitioners and
      non-practitioners.
AB  - BACKGROUND: Pilates exercises help stabilize the vertebral segments by recruiting
      the abdominal and spinal muscles. Pilates training may increase joint stability
      and improve neuromuscular efficiency (NME). OBJECTIVE: This study aimed to
      evaluate NME of the multifidus (MU) muscle through electromyography (EMG)
      analysis and torque test, applied to practitioners and non-practitioners of
      Pilates. METHODS: Participants included thirty women: Pilates practitioners (n =
      15) and non-practitioners (n = 15). They were tested for trunk extension. Their
      right and left MU muscles were submitted to EMG to estimate NME. Results
      concerning torque, EMG, and NME from all participants were compared. RESULTS:
      Statistical analysis concerning isometric torque peak (p = 0.0275) and NME (p =
      0.0062) showed significant difference (Student t test; p < 0.05) between
      practitioners and control. No significant difference (p = 0.3387) in EMG was
      observed. CONCLUSION: Our results suggest Pilates exercises is effective in
      training spinal muscles to improve NME in women.

PMID- 30219472
TI  - Visuospatial exploration and art therapy intervention in patients with
      Parkinson's disease: an exploratory therapeutic protocol.
AB  - Though abnormalities of visuospatial function occur in Parkinson's disease, the
      impact of such deficits on functional independence and psychological wellbeing
      has been historically under- recognized, and effective treatments for this
      impairment are unknown. These symptoms can be encountered at any stage of the
      disease, affecting many activities of daily living, and negatively influencing
      mood, self-efficacy, independence, and overall quality of life. Furthermore,
      visuospatial dysfunction has been recently linked to gait impairment and falls,
      symptoms that are known to be poor prognostic factors. Here, we aim to present an
      original modality of neurorehabilitation designed to address visuospatial
      dysfunction and related symptoms in Parkinson's disease, known as "Art Therapy".
      Art creation relies on sophisticated neurologic mechanisms including shape
      recognition, motion perception, sensory-motor integration, abstraction, and eye
      hand coordination. Furthermore, art therapy may enable subjects with disability
      to understand their emotions and express them through artistic creation and
      creative thinking, thus promoting self-awareness, relaxation, confidence and self
      efficacy. The potential impact of this intervention on visuospatial dysfunction
      will be assessed by means of combined clinical, behavioral, gait kinematic,
      neuroimaging and eye tracking analyses. Potential favorable outcomes may drive
      further trials validating this novel paradigm of neurorehabilitation.

PMID- 30219471
TI  - Chronic musculoskeletal pain and function improve with a plant-based diet.
AB  - BACKGROUND: Chronic musculoskeletal pain, often debilitating, affects all
      genders, ethnicities, and age groups. Research suggests consumption of a plant
      based diet may improve the status of persons with chronic pain. A diet rich in
      fruits, vegetables and whole grains has been shown to reduce chronic pain and
      disability associated with musculoskeletal conditions. OBJECTIVE: The purpose of
      this study was to examine the value of a plant-based diet in the management of
      chronic musculoskeletal pain and functional limitations. METHOD: Fourteen
      subjects participated in the eight-week study. Baseline evaluation included
      anthropometric measurements and completion of two self-reported outcome measures:
      Numeric Pain Rating Scale (NPRS) and the Short Form Health Survey (SF-36). A
      registered dietitian nutritionist provided a sample menu cycle and education on a
      plant-based diet. Subjects utilized a phone app to log food intake and receive
      support from the dietitian. Post data collection included a repeat of the
      baseline measures and the Patient Global Impression of Change Scale. The sample
      was small. Twenty subjects began, 14 completed. No comparison group was used.
      Results should be considered with caution. RESULTS: The diet intervention
      resulted in decreased pain and improvement in quality of life. Diet adherence by
      ten of fourteen subjects was 89% based on completion of food intake records and
      adherence to allowed foods. CONCLUSION: Consumption of a plant-based diet
      produced positive improvements in chronic pain and function. Interprofessional
      collaboration between physical therapists and registered dietitian nutritionists,
      along with other healthcare practitioners, can encourage and promote diet
      interventions that positively affect chronic pain.

PMID- 30219473
TI  - Complementary and alternative medicine in patients with inflammatory bowel
      disease: A survey performed in a tertiary center in Chile.
AB  - OBJECTIVES: The aim of this study was to assess the type and prevalence of
      complementary and alternative medicine (CAM) use in patients with inflammatory
      bowel disease (IBD) who are treated at our center. DESIGN: Observational, cross
      sectional questionnaire-based study that included patients from the IBD program
      of our center. SETTING: Tertiary clinical center in Santiago, Chile. MAIN OUTCOME
      MEASURES: Types of CAM being used by patients with IBD. RESULTS: A total of 200
      patients were included, 68% ulcerative colitis, 29% Crohn's disease, and 3% non
      classifiable IBD. Overall, 25% of the patients reported current use of CAM, 30%
      reported using in it the past, and 45% indicated that they had never used it
      before. The use of CAM was recommended in 20% of the patients by other healthcare
      professionals and in 10% of the patients by the gastroenterologist. Forty-nine
      percent of the patients informed the gastroenterologist that they were using CAM.
      Overall, 86% of the patients did not modify the conventional medical treatment
      (CMT). None of the patients who were using curcumin, homeopathic medicine,
      acupuncture or biomagnetism modified the CMT. CONCLUSIONS: The type of CAM being
      used plays an important role when the patient makes the decision to inform the
      gastroenterologist. Other healthcare professionals play an important role in
      providing the advice to start CAM. Gastroenterologists must be aware of the high
      prevalence of CAM use in IBD patients, actively ask about CAM use and guide the
      patients who want to use CAM in a responsible and safe manner.

PMID- 30219474
TI  - Effect of sumac (Rhus Coriaria) on blood lipids: A systematic review and meta
      analysis.
AB  - Cardiovascular diseases (CVD) are the prominent cause of mortality worldwide.
      Hypercholesterolemia is a chief risk factor for the progress of atherosclerotic
      vascular disease. Complementary and alternative medicine (CAM) such as herbal
      interventions has received much attention in literature. Rhus Coriaria (RC) with
      the general name Sumac is a medicinal spice, especially in Middle Eastern
      countries which is well known as an anti-lipid spice. This study aimed to
      summarize the existing findings regarding the effect of RC on the lipid profile.
      In this review randomized controlled trials (RCTs) assessing the effect of RC on
      blood lipids were included. Electronic searches using the MeSH terms were
      conducted in the following databases: Medline, Embase, Scopus, Web of Science and
      The Cochrane Library. The effect of RC on serum lipid concentration were measured
      as standardized mean difference (SMD) and 95% confidence intervals (CI) by the
      random-effects model. The initial search extracted 119 potentially relevant
      articles. After studying these publications, 4 were potentially eligible and
      retrieved in full text (four RCTs). Based on the results of the systematic
      review, RC has positive effects on different indices of the lipid profile
      including increasing Apo A-I and HDL; decreasing Apo B, Apo B/ Apo A1 ratio,
      total cholesterol, LDL and triglyceride. However the meta-analysis conducted on
      three studies on total cholesterol, HDL, LDL and triglyceride individually did
      not show any significant difference between intervention and control groups. No
      definite conclusion could be made on the effect of RC on serum blood lipids due
      to lack of sufficient clinical trials and variable inconsistency. Future trials
      with desirable designs that would eliminate the limitations in the current
      evidence are needed before conclusive claims can be made about the effect of RC
      on the lipid profile.

PMID- 30219475
TI  - Safety and efficacy of Melissa officinalis (lemon balm) on ApoA-I, Apo B, lipid
      ratio and ICAM-1 in type 2 diabetes patients: A randomized, double-blinded
      clinical trial.
AB  - BACKGROUND: The purpose of this study was to investigate the safety and effects
      of Melissa officinalis, a good source of bioactive components, on apolipoprotein
      (Apo)B, Apo A-I, and their ratio, lipids ratios and intercellular adhesion
      molecule-1(ICAM-1) in patients with type 2 diabetes. METHODS: For the present
      randomized, double-blinded, placebo-controlled clinical trial, 70 type 2 diabetic
      patients aged 20-65 years old were randomly assigned to receive hydroalcoholic
      extract of M. officinalis (HEMO) (700 mg/d) or placebo twice-daily for 12 weeks.
      RESULTS: There were significant differences in serum Apo A-I, TC/ HDL-c and LDL
      c/ HDL-c between the two groups at the end of the study (p < 0.05), but we did
      not show significant differences in the values for Apo B, Apo B/Apo A-I, TG/HDL
      c, ICAM-1 and liver enzymes include AST, ALT, and ALP between the study groups.
      Although both groups showed a significant reduction in ICAM-1, AST and, ALP (p <
      0.05), no significant differences in ICAM-1, AST and, ALP were observed. At end,
      in M. officinalis group, there was a significant increase in Apo A-I (p = 0.003)
      and significant reduction in TG/HDL-c (p = 0.05) compared with initial values, as
      well as in placebo group, there was a significant rising in Apo B/Apo A-I (p =
      0.02) and significant reduction in Apo A-I (p = 0.001) compared with baseline
      values. CONCLUSIONS: M. officinalis is safe and effective in improvement of Apo A
      I, Apo B/Apo A-I, and lipids ratios as key factors promoting cardiovascular
      disease (CVD) in type II diabetic patients.

PMID- 30219476
TI  - Mindfulness and avoidance mediate the relationship between yoga practice and
      anxiety.
AB  - OBJECTIVES: There is accumulating evidence that yoga and mindfulness meditation
      can alleviate symptoms of anxiety, although the mechanisms by which this occurs
      remain unclear. The purpose of this study was to examine the relationship between
      yoga practice and self-reported anxiety as well as the potential mediating roles
      of mindfulness and emotional avoidance. METHODS: Using a cross-sectional design,
      367 participants were recruited online and completed measures of anxiety,
      avoidance, and mindfulness. RESULTS: Results showed that length of yoga practice
      was significantly correlated with lower anxiety in yoga practitioners. Avoidance
      and mindfulness mediated the relationship between length of yoga practice and
      anxiety, shedding light on possible mechanisms by which these practices reduce
      anxiety. CONCLUSIONS: Future experimental and longitudinal research is needed to
      examine the causal role of mindfulness and avoidance in the relationship between
      yoga practice and anxiety, and whether yoga is a useful adjunct to cognitive
      behaviour therapy for anxiety disorders.

PMID- 30219478
TI  - Announcing 2019 and 2020 Virtual Special issues (VSIs).

PMID- 30219477
TI  - Are personalized tongxie formula based on diagnostic analyses more effective in
      reducing IBS symptoms?-A randomized controlled trial.
AB  - OBJECTIVES: To examine the efficacy and safety ofpersonalized tongxie formulas;
      to decrease type II errors to minimum. METHODS: Patients were randomized (1:1:1)
      into three groups given tongxie, placebo, or pinaverium 3 times daily for 4
      weeks. Patients in the tongxie group were treated with personalized formulas
      based on TCM differential diagnosis, i.e., basic type of IBS, IBS due to liver
      depression and qi stagnation, excess heat in the liver, deficient spleen
      function, deficient kidney function, and others (groups 1-6). Primary endpoints
      were significantly greater reductions in abdominal pain and Bristol stool score.
      Secondary endpoints were reductions in pain and stool frequencies and abdominal
      discomfort and its frequency. RESULTS: There were significantly more patients
      whose stool consistencies were improved than pains were relieved in the entire
      population (p < 0.001), but there was no significantly difference in
      subpopulation group 3 (p > 0.05). There were significantly more patients whose
      stool frequencies were reduced than pain frequencies were reduced in the entire
      population (p < 0.001), but there were no significantly difference in the
      subpopulation Groups 1, 3, 4, and 6 (p > 0.05). Multiple active ingredients and
      their mechanisms of actions to relieve IBS symptoms were identified. CONCLUSION:
      The outcomes in subpopulations may be different from those of the entire
      population, indicating that personalized formulas are important to achieve
      optimal outcomes; the active ingredients and innovative mechanisms identified in
      this study can be the candidates for developing new IBS drugs, and used to manage
      IBS, respectively. TRIAL REGISTRATION: NCT01641224 (www.ClinicalTrials.gov).

PMID- 30219479
TI  - The relationship between estimated bone strength by finite element analysis at
      the peripheral skeleton to areal BMD and trabecular bone score at lumbar spine.
AB  - Bone strength, estimated by finite element (FE) analysis based on high resolution
      peripheral quantitative computed tomography (HR-pQCT) images is an important
      contributor to understanding risk of fracture. However, it is a peripheral device
      and cannot be evaluated in vivo at lumbar spine L1-L4. The aim of this study was
      to investigate if the axial bone quality can be predicted by strength
      measurements of peripheral bone. Peripheral bone microarchitecture, areal bone
      mineral density (aBMD) and trabecular bone score (TBS) were measured in adults
      individuals (n = 262, 60 years and older; 63% women). Stiffness and failure load
      were estimated by FE analysis at HR-pQCT images at radius and tibia. Areal BMD
      and TBS were measured by dual energy X-ray absorptiometry (DXA) at L1-L4.
      Correlations between peripheral and axial data were estimated for each gender
      adjusted by age, weight, and height. Areal BMD L1-L4 resulted in weak to moderate
      significant correlations with stiffness and failure load at radius (women: R2 =
      0.178, p < 0.05 and R2 = 0.187, p < 0.001, respectively; men: R2 = 0.454 and R2 =
      0.451, p < 0.001, respectively) and at tibia (women: R2 = 0.211 and R2 = 0.216, p
      < 0.001, respectively; men: R2 = 0.488 and R2 = 0.502, p < 0.001, respectively).
      TBS showed a very weak or no correlation with stiffness and failure load at
      radius (women: R2 = 0.148 and R2 = 0.150, p < 0.05, respectively; men: R2 = 0.108
      and R2 = 0.106, p < 0.05, respectively) and at tibia (women: R2 = 0.146 and R2 =
      0.150, p < 0.05, respectively; men: R2 = 0.072 and R2 = 0.078, respectively).
      These data suggest that aBMD L1-L4 was better explained by peripheral bone
      strength characteristics than the TBS, mainly in men and tibia is generally the
      site with a better relationship.

PMID- 30219481
TI  - Looking beyond the mirror: Psychological distress; disordered eating, weight and
      shape concerns; and maladaptive eating habits in lawyers and law students.
AB  - Research indicates that, in comparison to professionals and University students
      in other disciplines, lawyers and law students may be at greater risk of
      experiencing high levels of psychological distress. There is also a large body of
      literature supporting an association between stress, anxiety and depression and
      unhealthy eating. This article reports on the results of a study of Australian
      legal professionals and law students that evidence a positive association between
      psychological distress; disordered eating, weight and shape concerns; and
      maladaptive eating habits in lawyers and law students. Additionally, this study
      confirms a positive link between frequency of exercise and subjective physical
      well-being, that in turn is associated with enhanced emotional well-being. Based
      on the results of this study, we suggest simple yet effective strategies law
      firms and law schools might adopt to support the mental health of their staff and
      students.

PMID- 30219482
TI  - Child's play: Harnessing play and curiosity motives to improve child handwashing
      in a humanitarian setting.
AB  - In humanitarian emergency settings there is need for low cost and rapidly
      deployable interventions to protect vulnerable children, in- and out-of-school,
      from diarrhoeal diseases. Handwashing with soap can greatly reduce diarrhoea but
      interventions specifically targeting children's handwashing behaviour in
      humanitarian settings have not been tested. Traditional children's handwashing
      promotion interventions have been school-focused, resource-intensive and reliant
      on health-based messaging. However, recent research from non-humanitarian
      settings and targeting adults suggests that theory-based behaviour change
      interventions targeting specific motives may be more effective than traditional
      handwashing interventions. In this proof-of-concept study we test, for the first
      time, the distribution of a modified soap bar, designed to appeal to the motives
      of play and curiosity, in a household-level, rapidly deployable, handwashing
      promotion intervention for older children in a humanitarian setting - an
      internally displaced persons camp in Iraqi Kurdistan. Out of five total blocks
      within the camp, one was assigned to intervention and one to control. 40
      households from each assigned block were then randomly chosen for inclusion in
      the study and the practice of handwashing with soap at key times was measured at
      baseline and four weeks after intervention delivery. Children in intervention
      households received transparent soaps with embedded toys, delivered within a
      short, fun, and interactive household session with minimal, non-health-based,
      messaging. The control group received plain soap delivered in a short standard,
      health-based, hygiene promotion session. At the 4-week follow-up, children in the
      intervention group were 4 times more likely to wash their hands with soap after
      key handwashing occasions than expected in the counterfactual (if there had been
      no intervention) based on the comparison to children in the control group
      (adjusted RR = 3.94, 95% CI 1.59-9.79). We show that distributing soaps with toys
      embedded inside, in a rapidly deployable intervention, can improve child
      handwashing behaviour in a humanitarian emergency context. Further studies are
      needed to determine the longer-term behavioural and health impact of such an
      intervention when delivered at a greater scale in a humanitarian context.

PMID- 30219483
TI  - Acute morphine administration alters the power of local field potentials in
      mesolimbic pathway of freely moving rats: Involvement of dopamine receptors.
AB  - Increasing number of evidence support the role of ventral tegmental area (VTA)
      and nucleus accumbens (NAc) in mediating the opiate effects as the two critical
      components of brain reward pathway. It is believed that VTA to NAC dopaminergic
      projections mediate the reinforcing effects induced by opioid drugs. Although
      numerous studies have investigated mechanisms of reward processing in these brain
      regions, alterations of local field potentials (LFPs), as an index of total
      synaptic currents, has not been previously addressed. In the present study, thin
      metal electrodes were implanted in both VTA and shell sub-region of NAc to
      simultaneously record the spontaneous LFPs in freely moving rats. After one week
      recovery period, a single dose of morphine was systemically administered and the
      LFP recording was performed 15, 30, 45 and 60 post-injection. Also, in order to
      assess the role of dopamine system, two groups of animals were pre-treated by
      selective antagonists of dopamine type-1 and type-2 receptors 15 min prior to
      morphine injection. The obtained results indicated that in VTA, acute morphine
      administration potentiates the power of all LFP frequency bands (i.e. delta,
      theta, alpha, beta and gamma). However, in NAc shell, theta wave was
      significantly attenuated by morphine and other components were not affected. In
      addition, pre-treatment with both antagonists prevented the observed effect of
      morphine on LFP power suggesting the involvement of dopamine receptors in this
      process. Future studies should address mechanisms of dopamine-morphine
      interactions. It is also valuable to focus on acute and chronic effects of
      morphine on LFP power and assessment of the observed effects following naloxone
      challenge.

PMID- 30219484
TI  - Involvement of angiotensin-(1-7) in the neuroprotection of captopril against
      focal cerebral ischemia.
AB  - Accumulating evidence suggests that brain angiotensin-converting enzyme
      (ACE)/angiotensin II/angiotensin II type I receptor axis is activated and thus
      contributes to the neuronal injury during ischemic stroke. Conversely, inhibition
      of this axis using centrally active ACE inhibitor captopril was proven
      neuroprotective in rodents with focal cerebral ischemia. Interestingly, captopril
      was able to increase angiotensin-(1-7) [Ang-(1-7)] levels in the peripheral
      organs. As the main component of the alternative renin-angiotensin system axis in
      the brain, Ang-(1-7) was revealed to protect against focal cerebral ischemia via
      a MAS1 receptor-dependent manner. Based on this evidence, we hypothesized that
      Ang-(1-7) might contribute to the neuroprotection of captopril during ischemic
      stroke. In this study, we evaluated this hypothesis using a rat model of focal
      cerebral ischemia. We revealed that brain ACE2 activity and Ang-(1-7) levels were
      significantly elevated following captopril treatment in rats with focal cerebral
      ischemia. More importantly, we showed that the neuroprotection provided by
      captopril was partially reversed by A-779, an antagonist for Ang-(1-7) receptor
      MAS1, indicating that Ang-(1-7) was involved in the neuroprotection of captopril.
      These findings have uncovered new mechanisms by which captopril protects against
      focal cerebral ischemia and further suggest that captopril may have practical
      clinical use for stroke prevention and treatment in addition to its
      antihypertensive effect.

PMID- 30219480
TI  - Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced
      heterotopic ossification in vitro cell culture model.
AB  - Trauma-induced heterotopic ossification is an intriguing phenomenon involving the
      inappropriate ossification of soft tissues within the body such as the muscle and
      ligaments. This inappropriate formation of bone is highly prevalent in those
      affected by blast injuries. Here, we developed a simplified cell culture model to
      evaluate the molecular events involved in heterotopic ossification onset that
      arise from the shock wave component of the disease. We exposed three subtypes of
      human mesenchymal cells in vitro to a single, high-energy shock wave and observed
      increased transcription in the osteogenic master regulators, Runx2 and Dlx5, and
      significantly accelerated cell mineralisation. Reduced representation bisulfite
      sequencing revealed that the shock wave altered methylation of gene promoters,
      leading to opposing changes in gene expression. Using a drug to target ITGAV,
      whose expression was perturbed by the shock wave, we found that we could abrogate
      the deposition of mineral in our model. These findings show how new therapeutics
      for the treatment of heterotopic ossification can be identified using cell
      culture models.

PMID- 30219485
TI  - Effects of low- and high-frequency repetitive transcranial magnetic stimulation
      on long-latency auditory evoked potentials.
AB  - Long-latency auditory event potentials (LLAEPs) involving local and global
      auditory processes have been investigated to examine the impact of low-frequency
      (LF) and high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS)
      on the cortical excitability of the temporal cortex. We hypothesized that both
      stimulation frequencies have the same modulation effect, in accordance with
      clinical data showing a reduction in auditory verbal hallucinations (AVHs) after
      LF and HF temporal rTMS in patients with schizophrenia. With 30 right-handed
      healthy volunteer participants enrolled in a crossover trial, we analyzed LLAEPs
      before and after LF- and HF-rTMS of the left temporal cortex. While we observed
      no changes in latencies, we did observe a similar inhibitory action of both rTMS
      frequencies on LLAEP amplitudes. Analysis of surface potential maps and cortical
      generators revealed some differences regarding auditory processes: HF-rTMS
      produced earlier, more diffuse, and more right-lateralized effects than LF-rTMS.
      Beyond a local impact, rTMS exerted a remote modulation influence on the frontal
      cortex that might be involved in attentional processes. This association could
      explain the therapeutic effect of temporal HF-rTMS on AVH.

PMID- 30219486
TI  - Proteasome limits plasticity-related signaling to the nucleus in the hippocampus.
AB  - Proteolysis by the ubiquitin-proteasome pathway has pleiotropic effects on both
      induction and maintenance of long-term synaptic plasticity. In this study, we
      examined the effect of proteasome inhibition on signaling to the nucleus during
      late-phase long-term potentiation. When a subthreshold L-LTP induction protocol
      was used, proteasome inhibition led to a significant increase in phosphorylated
      CREB (pCREB) in the nucleus. Inhibitors of cAMP-dependent protein kinase/protein
      kinase A, extracellular signal-regulated kinase and cGMP-dependent protein
      kinase/protein kinase G all blocked the proteasome-inhibition-mediated increase
      in nuclear pCREB after subthreshold stimulation. These results lay the groundwork
      for understanding a novel role for the proteasome in limiting signaling to the
      nucleus in the absence of adequate synaptic stimulation.

PMID- 30219487
TI  - Association between serum malondialdehyde levels and depression during early
      methamphetamine withdrawal.
AB  - Some evidence suggested that malondialdehyde (MDA) as a marker of oxidative
      stress played an important part in modulating the activities of depression.
      Methamphetamine (METH) dependence often lead to depression that may associate
      with MDA. In this study, our purpose was to explore the association between serum
      MDA levels and depression during METH withdrawal. 179 METH-dependent patients
      were recruited in this study and 144 (80.4%) finished the assessment. We measured
      serum MDA at 532 nm spectrophotometrically at admission. The short form of the
      Beck Depression Inventory (BDI-13) was used to evaluate depression symptoms.
      Patients were identified to have depression symptoms with the BDI score >= 8. As
      a result, 89 (61.8%) of the remaining 144 METH-dependent patients were identified
      to have depression symptoms. Patients with depression symptoms showed
      significantly higher serum MDA levels than non-depression patients (3.42 +/- 1.60
      nmol/ml vs. 2.43 +/- 1.25 nmol/ml; p <  0.001). After controlling for potential
      confounding variables in our logistic model, serum MDA levels were independently
      associated with the development of depression during early METH withdrawal (OR
      =1.952, 95% CI, 1.414-2.694, p < 0.001). Furthermore, our study found a positive
      association between Beck Depression Inventor (BDI) score in early METH abstinence
      and serum MDA levels (r =0.185; p =  0.026). Our results indicated that higher
      serum MDA levels were related to higher risk of depression symptoms during early
      METH withdrawal.

PMID- 30219488
TI  - The perception of sub-clinical personality disorders by employers, employees and
      co-workers.
AB  - This study set out to determine people's perceptions of different dark-side
      personality types in the workplace. A total of 240 adults with at least one
      year's work experience rated vignettes describing job candidates with sub
      clinical PDs. PDs were grouped into (Hogan and Hogan's 1997) personality clusters
      'Moving Away from', 'Moving Against' and 'Moving Toward' others. PDs in the
      Moving Toward cluster were rated as the most desirable employees. Participants
      were least willing to work with or for PDs in the Moving Against cluster. Moving
      Against candidates were perceived as less successful than Moving Towards
      candidates, suggesting that people believe the costs of working with people with
      many PDs (e.g. psychopathy and narcissism) outweigh any benefits there may be.
      Implications and limitations are noted.

PMID- 30219489
TI  - Evidence suggests a need to rethink social capital and social capital
      interventions.
AB  - In the 21 years since social capital first appeared in the public health
      literature, the evidence base has grown enormously, now reaching 28 systematic
      reviews encompassing more than 850 individual studies. We summarise this evidence
      and explain why conclusions relating to both the relationship between social
      capital and health, and the effectiveness of interventions to promote population
      health remain elusive and contradictory. A critical factor is the inadequate way
      that context is treated in the research, and especially how context interacts
      with efforts to promote health in a dynamic fashion. Of all the different types
      of interventions one could employ to improve the health of the public, 'social
      capital' interventions are likely to be the most context specific and especially
      affected by the boundaries placed around the context. A way forward is offered
      that requires a combination of insights from systems thinking, community-based
      participatory research, and intervention and improvement sciences. This requires
      renewed focus on the specific components of social capital, an understanding of
      how context interacts dynamically with efforts to improve health, a greater role
      for practice in the design, implementation, adaptation and evaluation of
      interventions, and the support of researchers to develop better methods for
      recognising and classifying the knowledge generated by complex interventions.

PMID- 30219490
TI  - Changing labour market conditions during the 'great recession' and mental health
      in Scotland 2007-2011: an example using the Scottish Longitudinal Study and data
      for local areas in Scotland.
AB  - This paper reports research exploring how trends in local labour market
      conditions during the period 2007-2011 (early stages of the 'great recession')
      relate to reported mental illness for individuals. It contributes to research on
      spatio-temporal variation in the wider determinants of health, exploring how the
      lifecourse of places relates to socio-geographical inequalities in health
      outcomes for individuals. This study also contributes to the renewed research
      focus on the links between labour market trends and population health, prompted
      by the recent global economic recession. We report research using the Scottish
      Longitudinal Study (SLS), a 5.3% representative sample of the Scottish
      population, derived from census data (https://sls.lscs.ac.uk/). In Scotland,
      (2011) census data include self-reported mental health. SLS data were combined
      with non-disclosive information from other sources, including spatio-temporal
      trends in labour market conditions (calculated using trajectory modelling) in the
      32 local authority areas in Scotland. We show that, for groups of local
      authorities in Scotland over the period 2007-2011, trends in employment varied.
      These geographically variable trends in employment rates were associated with
      inequalities in self-reported mental health across the country, after controlling
      for a number of other individual and neighbourhood risk factors. For residents of
      regions that had experienced relatively high and stable levels of employment the
      odds ratio for reporting a mental illness was significantly lower than for the
      'reference group', living in areas with persistently low employment rates. In
      areas where employment declined markedly from higher levels, the odds ratio was
      similar to the reference group. The findings emphasise how changes in local
      economic conditions may influence people's health and wellbeing independently of
      their own employment status. We conclude that, during the recent recession, the
      economic life course of places across Scotland has been associated with
      individual mental health outcomes.

PMID- 30219491
TI  - A unique case of buffalo hump after prolonged use of spironolactone.

PMID- 30219492
TI  - Drugs That Improve Cardiovascular Prognosis in Diabetes and Are Not Yet Used by
      Cardiologists.

PMID- 30219493
TI  - Intimate Partner Relationships, Work-Life Factors, and Their Associations with
      Burnout Among Partnered Pediatric Residents.
AB  - BACKGROUND: Burnout is prevalent among pediatric residents, and reducing burnout
      is a priority for pediatric residency programs. Understanding residents' personal
      circumstances, including relationship satisfaction and perceived work-life
      conflict, may identify novel determinants of burnout. OBJECTIVES: To describe
      intimate partner relationships among pediatric residents and examine associations
      among relationship satisfaction, work-life factors, and burnout. METHODS: We
      identified 203 partnered residents (married or in a self-identified committed,
      ongoing relationship) from a cross-sectional survey of 258 residents in 11 New
      England pediatric programs (response rate 54% of 486 surveys distributed),
      conducted from April through June of 2013. We analyzed associations among
      relationship satisfaction, work-life factors, and burnout using multivariable
      regression. Burnout was measured with the brief Maslach Burnout Inventory, and
      relationship satisfaction with the validated Relationship Assessment Scale.
      RESULTS: Burnout was reported by 40.9% of partnered respondents. The vast
      majority of partnered residents (n = 167; 85.2%) reported high relationship
      satisfaction. Lower relationship satisfaction was not associated with burnout.
      Approximately half of the respondents (n = 102; 51.5%) reported being satisfied
      with life as a resident. When controlling for common stressors, such as sleep
      deprivation, work-life measures associated with burnout included frequent
      perceived conflicts between personal and professional life (adjusted odds ratio,
      4.35; 95% confidence interval, 1.91-9.88) and dissatisfaction with life as a
      resident (adjusted odds ratio, 11.74; 95% confidence interval, 4.23-32.57).
      CONCLUSION: Low relationship satisfaction and common work-life stressors were not
      associated with burnout among partnered pediatric residents. However, perceived
      work-life conflict and dissatisfaction with resident life were strongly
      associated with burnout and are targets for residency programs seeking to
      ameliorate burnout.

PMID- 30219495
TI  - Adsorption of Cu2+, Pb2+, and Cd2+ onto oiltea shell from water.
AB  - Agro-processing waste oiltea shell (OTS) has been previously proven effective in
      removing dye from water by adsorption. This study further evaluated its
      capability to adsorb heavy metals in aqueous solution. Adsorbent dosage, pH, ion
      concentration, temperature, and contact time were investigated in batch
      experiments. Pseudo-second order kinetic better described the adsorption process
      for the three ions. Langmuir equation was more suitable for Cu2+ and Cd2+, while
      Freundlich for Pb2+. The maximum adsorption capacity was 22.4 (Pb2+), 12.1
      (Cu2+), and 14.2 mg/g (Cd2+), respectively. The adsorption was spontaneous and
      endothermic. Adsorption was then performed in column and Thomas model was fitted,
      based on which the maximum adsorption capacity was 7.42 (Cu2+), 4.17 (Pb2+), and
      18.02 mg/g (Cd2+), respectively. High removal rate of metal ions and dye
      methylene blue was also achieved from their mixture solution. OTS is therefore a
      promising biosorbent in treating wastewater with organic and inorganic
      pollutants.

PMID- 30219494
TI  - Lignin depolymerization and utilization by bacteria.
AB  - Lignin compound wastes are generated as a result of agricultural and industrial
      practices. Microorganism-mediated bio-catalytic processes can depolymerize and
      utilize lignin eco-friendly. Although fungi have been studied since several
      decades for their ability to depolymerize lignin, strict growth conditions of
      fungus limit it's industrial application. Compared with fungi, bacteria can
      tolerate wider pH, temperature, oxygen ranges and are easy to manipulate. Several
      studies have focused on bacteria involved in the process of lignin
      depolymerization and utilization. Pseudomonas have been used for paper mill
      wastewater treatment while Rhodococcus are widely reported to accumulate lipid.
      In this review, the recent studies on bacterial utilization in paper wastewater
      treatment, lignin conversion to biofuels, bioplastic, biofertilizers and other
      value-added chemicals are summarized. As bacteria possess remarkable advantages
      in industrial production, they may play a promising role in the future commercial
      lignin utilization.

PMID- 30219496
TI  - Effects of influent COD/TN ratio on nitrogen removal in integrated constructed
      wetland-microbial fuel cell systems.
AB  - Given that the relationship between the influent C/N (generally referred to as
      COD/TN) ratio and nitrogen removal has not been well understood in integrated
      constructed wetland-microbial fuel cell (CW-MFC) systems, this study aimed to
      investigate the effects of COD/TN ratio on nitrogen removal in CW-MFCs. Results
      showed that the MFC could reduce the dependence of denitrification on organic
      carbon sources in CWs, and influent COD/TN ratios >=3 could result in a TN
      removal of 90.30-91.46% in CW-MFCs. Moreover, the MFC could significantly enhance
      TN removal by 4.81% to 15.48% when the influent COD/TN ratios decreased from 9.00
      to 1.23 in CWs. The lower the influent COD/TN ratio was, the stronger the
      enhancement of the MFC. There was a significant positive relationship (R2 > 0.99)
      between the electricity output and influent CODCr concentration (50-360 mg/L) in
      the CW-MFC.

PMID- 30219497
TI  - Corrections.

PMID- 30219498
TI  - Longitudinal assessment of clinical and inflammatory markers in patients with
      amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To evaluate potential associations between clinical features and
      inflammatory markers in patients with amyotrophic lateral sclerosis (ALS).
      METHODS: A consecutive series of 68 patients (39 males and 29 females) with
      sporadic ALS were subjected to a comprehensive clinical assessment and blood
      draw. A subset of these patients underwent a new assessment within 6-12 months
      after the baseline visit. In addition, a group of 62 subjects composed by age and
      sex-matched healthy subjects (38 males and 24 females) was enrolled in this
      study. Peripheral blood was drawn and plasma levels of chemokines and cytokines
      were measured by cytometric bead array and enzyme-linked immunosorbent assay.
      RESULTS: Our sample was composed by patients with ALS with an average age of 58
      (+/-12.3) years old and 3 (+/-2.7) years of disease length at the baseline visit.
      Patients with ALS presented increased plasma levels of interleukin (IL)-6 and IL
      8 in comparison with controls. After multivariate analysis, higher levels of IL-6
      and lower levels of IL-2 were significantly associated with increased likelihood
      of ALS diagnosis. When evaluating the subset of patients assessed longitudinally,
      we did not find any significant difference in the levels of inflammatory markers
      between the two time points. Older age at ALS onset was the only factor
      associated with a faster rate of disease progression. CONCLUSIONS: IL-6 levels
      could discriminate between ALS and controls and may be regarded as a potential
      biomarker of ALS diagnosis. An increase in IL-2 levels was associated with a
      protective effect on the odds of ALS diagnosis. Older age at ALS onset predicted
      a fast rate of disease progression.

PMID- 30219499
TI  - Impact of atrial fibrillation on the rate of mild cognitive impairment in the
      elderly.
AB  - Mild cognitive impairment (MCI) in patients with cardiovascular risks is a
      transitional state to vascular dementia but which still has a possibility of
      being managed. The objectives of this study were to assess the impact of atrial
      fibrillation (AF) on cognitive performances in the elderly in comparison with
      similar cardiovascular risks. One hundred unselected patients were included in
      AF+ and AF- groups. Patients with prodromal Alzheimer disease as shown by
      semantic cueing test, and those suffering from major cognitive decline according
      to DSM 5 criteria were evaluated separately from those patients analysed for
      vascular cognitive impairment. MCI was distinguished with the help of the
      Montreal cognitive assessment and the mood status was studied with the geriatric
      depression scale. AF+ patients predominantly had paroxysmal type of AF with a
      mean duration of 6.3 years, with 77% of the patients being on anticoagulation. AF
      patients had arterial hypertension. Prevalence of MCI was significantly higher
      among AF- patients, possibly due to lower rates of BP control. These study
      results show less impact of AF itself on cognitive performances in comparison
      with uncontrolled hypertension.

PMID- 30219500
TI  - Kind and distribution of cutaneous sensation loss in hereditary transthyretin
      amyloidosis with polyneuropathy.
AB  - OBJECTIVE: Report on the kind and distribution of somatotopic sensation loss and
      its utility in assessing severity of sensation loss in study of a large
      international cohort of patients with hereditary transthyretin amyloidosis with
      polyneuropathy (hATTR-PN). METHODS: Smart Somatotopic Quantitative Sensation
      Testing (S ST QSTing) using Computer Assisted Sensation Evaluator IVc (CASE IVc)
      was used to assess the somatotopic distribution of touch pressure (TP) and heat
      pain (HP) sensation loss twice of untreated hATTR-PN patients in the Ionis NEURO
      TTR trial (www.clinicaltrials.gov, NCT01737398). RESULTS: Of the studied cohort
      of 169 patients, 163 (97%) had sensation loss, both TP and HP in 121/169 (75%),
      TP only in 39/169 (23%), and HP only in 3/169 (2%). Sensation loss typically
      affected both lower (152/169-90%) and upper limb (135/169-82%), and overall TP
      sensation loss was greater than HP loss, except for early-onset Val30Met patients
      in which HP exceeded TP loss. CONCLUSION: Using S ST QSTing, a highly
      quantitated, standardized, referenced, and automated QSTing approach of the
      body's surface distribution of sensation loss we have shown that: 1) reliable and
      useful measurement of the body surface distribution of sensation loss is
      possible; 2) this measure is abnormal in most patients with hATTR-PN and is an
      indication of polyneuropathy severity; and 3) cutaneous sensation loss involves
      both large and small sensory fibers in this disease but slightly more small
      fibers in early onset Val30Met patients.

PMID- 30219502
TI  - UV-screening and springtime recovery of photosynthetic capacity in leaves of
      Vaccinium vitis-idaea above and below the snow pack.
AB  - Evergreen plants in boreal biomes undergo seasonal hardening and dehardening
      adjusting their photosynthetic capacity and photoprotection; acclimating to
      seasonal changes in temperature and irradiance. Leaf epidermal ultraviolet (UV)
      screening by flavonols responds to solar radiation, perceived in part through
      increased ultraviolet-B (UV-B) radiation, and is a candidate trait to provide
      cross-photoprotection. At Hyytiala Forestry Station, central Finland, we examined
      whether the accumulation of flavonols was higher in leaves of Vaccinium vitis
      idaea L. growing above the snowpack compared with those below the snowpack. We
      found that leaves exposed to colder temperatures and higher solar radiation
      towards the top of hummocks suffered greater photoinhibition than those at the
      base of hummocks. Epidermal UV-screening was highest in upper-hummock leaves,
      particularly during winter when lower leaves were beneath the snowpack. There was
      also a negative relationship between indices of flavonols and anthocyanins across
      all leaves suggesting fine-tuning of flavonoid composition for screening vs.
      antioxidant activity in response to temperature and irradiance. However, the
      positive correlation between the maximum quantum yield of photosystem II
      photochemistry (Fv/Fm) and flavonol accumulation in upper hummock leaves during
      dehardening did not confer on them any greater cross-protection than would be
      expected from the general relationship of Fv/Fm with temperature and irradiance
      (throughout the hummocks). Irrespective of timing of snow-melt, photosynthesis
      fully recovered in all leaves, suggesting that V. vitis-idaea has the potential
      to exploit the continuing trend for longer growing seasons in central Finland
      without incurring significant impairment from reduced duration of snow cover.

PMID- 30219501
TI  - Mechanisms of N-oleoyldopamine activation of central histaminergic neurons.
AB  - Histaminergic (HA) neurons located in the tuberomamillary nucleus (TMN) of the
      posterior hypothalamus fire exclusively during waking and support many
      physiological functions. We investigated the role of the endovanilloid N
      oleoyldopamine (OLDA) in TMN, where dopamine synthesis and its conjugation with
      oleic acid likely occur. We show that several known targets of OLDA including
      TRPV1 and cannabinoid receptors are expressed in HA neurons. In contrast to
      capsaicin, which failed to increase firing of HA neurons in TRPV1 knockout mice
      (TRPVI KO), OLDA was still able to induce excitation. This excitation was not
      sensitive to the blockade of cannabinoid receptors 1 and 2 and could result from
      OLDA interaction with GPR119, as the ligand of GPR119, oleoylethanolamide (OEA),
      also increased the firing of HA neurons. However, we ruled out this possibility
      as OEA- (but not OLDA-) excitation was abolished by the PPAR (peroxisome
      proliferator activated receptor) alpha antagonist MK886. The dopamine uptake
      blocker nomifensine blanked OLDA-excitation and dopamine receptor antagonists
      abolished the OLDA action in TRPV1 KO mice. Therefore OLDA excites HA neurons
      through multiple targets suggesting a central role of the histaminergic system in
      the behavioral stimulation seen after systemic OLDA application.

PMID- 30219503
TI  - A new diethylcarbamazine formulation (NANO-DEC) as a therapeutic tool for hepatic
      fibrosis.
AB  - The aim of the present study was to assess if the uninterrupted and prolonged
      administration of nanoparticles containing diethylcarbamazine (NANO-DEC) would
      cause liver, kidney and heart toxicity and then analyze for the first time its
      action in model of liver fibrosis. Thus, NANO-DEC was administered in C57BL/6
      mice daily for 48 days, and at the end the blood was collected for biochemical
      analyzes. In the long-term administration assay, the evaluation of serological
      parameters (CK-MB, creatinine, ALT, AST and urea) allowed the conclusion that
      NANO-DEC prolonged administration did not cause hepatic, renal and cardiac
      damage. For fibrosis assays, C57BL/6 mice were divided into six groups: 1)
      control (Cont); 2) carbon tetrachloride (CCl4); 3) CCl4 + DEC 25 mg/kg; 4) CCl4 +
      DEC 50 mg/kg; 5) CCl4 + NANO-DEC 5 mg/kg and 6) CCl4 + NANO-DEC 12.5 mg/kg.
      Carbon tetrachloride induced hepatic fibrosis observed through increased
      inflammatory (TNF-alpha, IL-1beta, COX-2, NO and iNOS) and fibrotic markers (TGF
      beta and TIMP-1), changes in the hepatic morphology, high presence of collagen
      fibers and elevated serum levels of AST, ALT and ALP. Treatment with NANO-DEC
      exhibited a superior anti-inflammatory and anti-fibrotic effects compared to the
      DEC traditional formulation, restoring liver morphology, reducing the content of
      collagen fibers and serological parameters, besides decreasing the expression of
      inflammatory and fibrotic markers. The present formulation of nanoencapsulated
      DEC is a well tolerated anti-inflammatory and anti-fibrotic drug and therefore
      could be a potential therapeutic tool for the treatment of chronic liver
      disorders.

PMID- 30219504
TI  - Forearm wearable resistance effects on sprint kinematics and kinetics.
AB  - OBJECTIVES: Arm swing is a distinctive characteristic of sprint-running with the
      arms working in a contralateral manner with the legs to propel the body in a
      horizontal direction. The purpose of this study was to determine the acute
      changes in kinematics and kinetics when wearable resistance (WR) of 1kg
      (equivalent to ~1% body mass) was attached to each forearm during over ground
      short distance (20m) maximal sprint-running. DESIGN: Cross-sectional study.
      METHODS: Twenty-two male amateur rugby athletes (19.4+/-0.5years; 97.0+/-4.8kg;
      180.4+/-7.2cm) volunteered to participate in the study. Radar and Optojump were
      used to examine kinematic and kinetics between WR and unloaded sprint-running
      conditions. RESULTS: No significant (p<0.05) differences were found at 2m or 5m
      between conditions, however, the WR condition resulted in a significant increase
      in 10m, 20m and 10-20m split time (all, ~2%, small effect size) compared to the
      unloaded condition. Significant decreases were also found in theoretical maximum
      velocity (V0) (-1.4%, small effect size) and relative peak horizontal power
      production (Pmax) (-5.5%, small effect size). Step length (2.1%, small effect
      size) and contact time (6.5%, medium effect size) were significantly increased,
      while step frequency (-4.1%, small effect size) and flight time (-5.3%, medium
      effect size) were significantly decreased. CONCLUSIONS: WR forearm loading
      provides a movement specific overload of the arms which significantly alters step
      kinematics and sprint times >=10m.

PMID- 30219505
TI  - Exosomes in virus-associated cancer.
AB  - Exosomes are phospholipid bilayer membrane-enclosed vesicles in a size from 30 to
      150 nm, carrying a variety of active components, such as proteins, mRNA and
      miRNAs, and are involved in intercellular communication. Exosomes are released by
      almost all living cells and detected in various biological fluids. Viruses
      especially oncogenic viruses have been reported to influence the formation of
      virus-associated cancer through reshaping the tumor microenvironment via
      exosomes. In this review, a role of exosomes released by oncogenic virus-infected
      cells in promoting or inhibiting cancer formation is outlined. Moreover, the
      prospects and challenges of exosome applications in cancer therapies are
      critically discussed.

PMID- 30219506
TI  - Melt-spun microbial poly(3-hydroxybutyrate-co-3-hydroxyvalerate) fibers with
      enhanced toughness: Synergistic effect of heterogeneous nucleation, long-chain
      branching and drawing process.
AB  - A series of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) composite fibers
      were prepared via melt reactive processing where tungsten disulphide (WS2) and
      dicumyl peroxide (DCP) was used as heterogeneous nucleating agent and initiator,
      respectively. Compared with PHBV or PHBV/WS2 fiber, the resultant LCB-PHBV/WS2
      fibers showed improving mechanical performance, a higher nucleation temperature
      and a rapid crystallization rate due to the synergistic effect between
      heterogeneous nucleation, long chain branched structure and draw-induced
      crystallization. Taking the results with a cooling rate of 20  degrees C/min as
      an example, the peak crystallization temperature of LCB-PHBV/1.0 wt%WS2 increased
      from 100.47  degrees C to 107.40  degrees C and the crystallization enthalpy
      increased from 87.95 J/g to 93.03 J/g. Moreover, two different crystalline forms,
      alpha-crystal and beta-crystal, were found in the prepared PHBV fibers, and the
      beta-crystal part increased with the inducement of the stretching ratio which
      enhanced the fiber strength, given the tensile strength and elongation at break
      of the LCB-PHBV/WS2 fibers up to 189.8 MPa and 46.5%, respectively.

PMID- 30219507
TI  - Organic solvent fractionation of acetosolv palm oil lignin: The role of its
      structure on the antioxidant activity.
AB  - Pressed palm oil mesocarp fibers (PPOMF) are by-products from oil palm industry
      and represents a potential source of lignocellulosic biomass. In order to add
      value to this agro-waste, dewaxed palm oil acetosolv lignin (DPOAL) was extracted
      under eco-friendly pulping method. The chemical composition and structural
      characteristics of DPOAL were investigated. The results showed elevated yield
      (48.5%) and high purity (94.3%), besides a moderate average molecular weight
      (1394 g mol-1) and narrow polydispersity index (1.88). Structural
      characterization via FT-IR, 1H13C HSQC and 31P NMR indicated that DPOAL was a
      typical HGS-type lignin. In addition, to increase the phenolic hydroxyl contents
      and improve DPOAL's antioxidant properties through a simple method, a
      fractionation process with methanol, ethanol and acetone was carried out,
      obtaining the methanol (MeOH-F), ethanol (EtOH-F) and acetone (ACT-F) soluble
      fractions. These were characterized by FT-IR, DSC, 1H13C HSQC and 31P NMR, which
      showed higher values of phenolic and aliphatic hydroxyls groups compared to
      DPOAL. The antioxidant activity was evaluated by the free radical scavenging
      activity of 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH.) and compared with
      commercial antioxidants, such as BHT and Irganox 1010. Interestingly, lignin
      samples had significantly lower IC50 values compared to commercial antioxidants,
      what suggests a great potential as novel natural antioxidant.

PMID- 30219508
TI  - Upregulated circular RNA circ-102004 that promotes cell proliferation in prostate
      cancer.
AB  - OBJECTIVE: Prostate cancer (PCa) is one of the most prevalent cancers affecting
      men worldwide. However, the biological functions of circRNAs in PCa are still
      largely unknown. METHODS: Real-time PCR (RT-PCR) and immunohistochemistry were
      performed to characterize the circ-102004 expression in both human PCa tissues
      and cell lines. The apoptosis and cell cycle status of prostate immortalized cell
      lines that were overexpressed with circ-102004 by transfection was analyzed using
      flow cytometry. The scratch test and the Transwell assay were conducted to
      evaluate the ability of transfected cells to migrate and invade. RNA sequencing,
      pathway analysis, and Western blotting were performed to probe the associations
      of circ-102004 with the classical cancer signaling pathways after functionally
      evaluating circ-102004 in a xenograft tumor model. RESULTS: In the present study,
      circ-102004 expression was found to be significantly higher in PCa samples than
      in the matched normal tissues. In functional experiments, circ-102004 is shown to
      play an oncogenic role in PCa by stimulating cancer cell migration and invasion.
      Circ-102004 overexpression was also accompanied by significant alterations in
      many signaling pathways, such as ERK, JNK, and Hedgehog, which are known to cause
      different types of cancers. CONCLUSIONS: Circ-102004 is a potential oncogenic
      gene that regulates the development and progression of PCa. This study provides a
      scientific basis for targeting circ-102004 for either diagnosis or therapy.

PMID- 30219509
TI  - Vaccination and immunization strategies to design Aedes aegypti salivary protein
      based subunit vaccine tackling Flavivirus infection.
AB  - Flavivirus causes arthropod-borne severe diseases that sometimes lead to the
      death. The Flavivirus species including Dengue virus, Zika virus and yellow fever
      virus are transmitted by the bite of Aedes mosquitoes. All these viral species
      target the people living in their respective endemic zone causing a high
      mortality rate. Recent studies show that immune factors present in the Ae.
      aegypti saliva is the hidden culprit promoting blood meal collection, suppressing
      host immune molecules and promoting disease establishment. This study was
      designed to develop a subunit vaccine using Aedes mosquito salivary proteins
      targeting the aforementioned Flaviviruses. Subunit vaccine was designed very
      precisely by combining the immunogenic B-cell epitope with CTL and HTL epitopes
      and also suitable adjuvant and linkers. Immunogenicity, allergenicity and
      physiochemical characterization were also performed for scientific validation.
      Molecular docking and molecular dynamics simulations studies were carried out to
      confirm the stable affinity between the vaccine protein (3D) and TLR3 receptor.
      At last, in silico cloning was executed to get the subunit vaccine restriction
      clone into pET28a vectro to express it in microbial expression system.
      Additionally, this study warrants the experimental evaluation for the validation
      purposes.

PMID- 30219510
TI  - Demonstration of the adhesive properties of the medium-chain-length
      polyhydroxyalkanoate produced by Pseudomonas chlororaphis subsp. aurantiaca from
      glycerol.
AB  - Pseudomonas chlororaphis subsp. aurantiaca (DSM 19603) was grown on crude
      glycerol from biodiesel production to produce a medium-chain-length
      polyhydroxyalkanoate (mcl-PHA), composed of 3-hydroxydodecanoate (43 +/- 1.8
      mol%), 3-hydroxydecanoate (29 +/- 3.1 mol%), 3-hydroxytetradecanoate (12 +/- 0.4
      mol%), 3-hydroxyoctanoate (10 +/- 1.5 mol%) and 3-hydroxyhexanoate (6 +/- 0.3
      mol%). The biopolymer had an average molecular weight of 1.1 * 105 Da, with a
      polydispersity index of 1.5, and was semi-crystalline, as shown by its
      crystallinity index of 37 +/- 0.2%. It had low melting (44  degrees C) and glass
      transition (-48  degrees C) temperatures, and was thermally stable up to 285 
      degrees C. The biopolymer films were elastic and translucid, were hydrophobic and
      presented relatively high permeability to oxygen and carbon dioxide. The films
      demonstrated to have good adhesion properties towards porcine skin and human
      skin. The tension (61.1 +/- 20.6 kPa) and shear (12.7 +/- 2.14 kPa) bond strength
      of the mcl-PHA for porcine skin suggest its potential as a biomaterial for the
      development of novel natural adhesives for wound closure or wound dressings.

PMID- 30219511
TI  - Bioassays: The best alternative for conventional methods in detection of
      Legionella pneumophila.
AB  - Fastidious bacteria are group of bacteria that not only grow slowly but also have
      complex nutritional needs. In this review, recent progress made on development of
      biosensing strategies towards quantification of Legionella pneumophila as
      fastidious bacteria in microbiology was investigated. In coincidence with medical
      bacteriology, it is the most widely used bio-monitoring, biosensors based on DNA
      and antibody. Also, all of legionella pneumophila genosensors and immunosensors
      that developed in recent years were collected analyzed. This review is meant to
      provide an overview of the various types of bioassays have been developed for
      determination of Legionella Legionella, along with significant advances over the
      last several years in related technologies. In addition, this review described:
      i) Most frequently applied principles in bioassay/biosensing of Legionellaii) The
      aspects of fabrication in the perspective of bioassay/biosensing applications
      iii) The potential of various electrochemical and optical bioassay/biosensing for
      the determination of Legionella and the circumvention of the most serious problem
      in immunosensing/immunoassay was discussed. iv) Some of bioassay/biosensing has
      been discussed with and without labels. v) We also summarize the latest
      developments in the applications of bioassay/biosensing methods for detection of
      Legionella. vi) The development trends of optical and electrochemical based
      bioassay/biosensing are also introduced.

PMID- 30219512
TI  - Improving the retention and reusability of Alpha-amylase by immobilization in
      nanoporous polyacrylamide-graphene oxide nanocomposites.
AB  - Alpha-amylase was immobilized inside three different polymeric matrices:
      polyacrylamide hydrogel (PAAm), polyacrylamide-graphene oxide nanocomposite (PAAm
      GO) and alginate in order to study and compare the effect of the matrix on the
      catalytic performance. The morphology, swelling, mechanical properties, retention
      efficiency, and the catalytic behavior of these newly supported biocatalysts were
      studied. Nanocomposite made of PAAm-GO matrix incorporated 98% of the enzyme,
      likely through a cooperative effect, while alginate gels incorporated only 30%.
      Moreover, the enzyme retention using PAAm-GO reached a value of 97.5%. Starch
      hydrolysis catalyzed by the immobilized enzyme in PAAm-GO matrix showed similar
      kinetics profiles up to 5 cycles suggesting that the enzymatic activity is
      retained. These results compare very favorably with conventional immobilization
      in alginate where almost no activity was observed after 3 cycles. All results
      suggest that the PAAm matrices protect the biocatalyst allowing its reusability.
      Moreover, the improvements in enzyme catalytic properties via immobilization made
      this system as an excellent candidate in bio-industrial applications such as
      bioethanol production. Furthermore, the synthesized catalyst could produce a high
      yield of bioethanol by using enzymes and yeast immobilized in the same PAAm
      matrix. In this way, it is possible to produce sequential or simultaneous
      saccharification and fermentation.

PMID- 30219513
TI  - Transcriptome analysis reveals functional roles of nacreous protein N16 in
      prednisolone-induced osteoporotic zebrafish.
AB  - N16 is an active protein isolated and screened from nacre proteins. Our previous
      studies have shown that N16 exerted a good effect on osteoporosis caused by
      dexamethasone on female rats. In order to further confirm the action of N16
      against glucocorticoid-induced osteoporosis (GIOP) and clarify its possible
      mechanisms, prednisolone-treated larval zebrafish (Danio rerio) model was
      adopted. Administration of N16 resulted in a significant increase of vertebral
      bone density of osteoporotic zebrafish, indicating a good effect of N16 against
      GIOP. Transcriptomic sequencing analysis was then performed to investigate the
      mechanisms of the action of N16 against GIOP. It was observed that N16 modulated
      the osteoporotic phenotype by up-regulating the osteoblastic characteristic genes
      and down-regulating the osteoclastic characteristic genes in zebrafish.

PMID- 30219514
TI  - A self-targeting and controllable drug delivery system constituting mesoporous
      silica nanoparticles fabricated with a multi-stimuli responsive chitosan-based
      thin film layer.
AB  - Surface modification and functionalization of nanomaterials have been adopted
      widely in devising smart drug delivery systems. This work examines the
      fabrication of multi-stimuli responsive surfaces on mesoporous silica
      nanoparticles (MSN) for environmentally sensitive site specific drug delivery
      with reduced risk of premature drug leakage. Chitosan cross-linked via disulfide
      bonds was applied to form a thin film on drug-loaded MSN, realizing a capsulation
      and stimuli-sensitive regulating gate membrane; that was further conjugated with
      folate for site specific targeting toward cancer cells. The chitosan thin film
      was very stable under neutral conditions and could effectively prevent drug
      leakage, but was sensitive to both pH and GSH stimulations to reach rapid drug
      release. Thus, drug release could be triggered by changes in such factors that
      are common to cancer cells. However, complete and accelerated release could only
      be realized when triggered simultaneously by both acidic pH and GSH. Moreover,
      tests with HepG-2 cells confirmed that folate-receptor mediated endocytosis
      successfully enhanced the cellular uptake of the nanoparticle and antitumor
      activity toward cancer cells. It is expected that this surface chemical
      modification strategy promises a powerful approach constructing smart drug
      delivery systems for efficient and safe chemotherapy.

PMID- 30219515
TI  - Improved chemotherapy against breast cancer through immunotherapeutic activity of
      fucoidan decorated electrostatically assembled nanoparticles bearing doxorubicin.
AB  - Immunotherapeutic nanoparticles (NPs) could be a viable option for delivering
      cytotoxic agents in a manner which suppresses their toxic manifestations.
      Doxorubicin (DOX) loaded NPs were prepared using fucoidan (FCD), an
      immunomodulatory polysaccharide and evaluated against cancer. FCD was
      electrostatically assembled with cationic polyethylenimine (PEI) through
      intermolecular electrostatic interactions to develop an immunomodulatory platform
      to deliver DOX. FCD NPs offered improved cytotoxicity (2.64 folds), cell cycle
      arrest in G1-S phase (34.65%) and apoptosis (66.12%) in tumor cells compared to
      free DOX. The enhanced apoptosis was due to raised mitochondrial depolarization
      (88.00%). In vivo anticancer activity in 4T1 induced tumor bearing BALB/c mice
      demonstrated a 2.95 folds enhanced efficacy of NPs. Importantly, NPs treatment
      generated an immunotherapeutic response indicated by gradual increment of the
      plasma IL-12 levels and reversed polarization of tumor associated macrophages
      (TAMs) towards M1 subtype. Furthermore, pharmacokinetic study suggested that NPs
      administration in tumor infested mice caused serum DOX levels to vary in a
      biphasic pattern, with twin peaks occurring at 1 h and 6 h which help in
      maintaining preferential drug localization in tumor. Developed NPs would be an
      excellent approach for improved immune-chemotherapy (in terms of efficacy, safety
      and immunocompetency) against cancer.

PMID- 30219516
TI  - Ontogeny of QRFP and its receptor expression in mouse testis during post-natal
      development.
AB  - Pyroglutamylated RFamide peptide (QRFP), a neuropeptide, binds to its receptor
      GPR103 and influences various biological functions. In the present study,
      expression and localization of QRFP and GPR103 in mouse testis during post-natal
      development were investigated. The results showed that QRFP and GPR103 and also
      the isoforms of the receptor, viz. GPR103A and GPR103B were expressed in mouse
      testis during post-natal development. Expression of QRFP and its receptor was
      high during the early periods of post-natal development. Immunohistochemical
      study demonstrated the localization of QRFP and GPR103 in both interstitial and
      tubular compartments of the testis throughout post-natal development. A shift in
      the germ cell types expressing QRFP and its receptor along the course of
      testicular development and also a prominent immunoreactivity of QRFP in germ
      cells and of GPR103 in Sertoli cells was observed. Further, the immunoreactivity
      of QRFP and GPR103 appeared to be stage-specific in spermatogenetically active
      testis. Besides in intercellular spaces, localization of QRFP was also noticed in
      nuclei of germ cells. In conclusion, the present results suggest potential
      involvement of QRFP system in the development, proliferation and differentiation
      of testicular cells, possibly by regulating the energy requirement for these
      processes.

PMID- 30219517
TI  - A novel beta-xylosidase from Anoxybacillus sp. 3M towards an improved agro
      industrial residues saccharification.
AB  - An intracellular beta-xylosidase (AbXyl), from the thermoalkaline Anoxybacillus
      sp. 3M, was purified and characterized. The homodimeric enzyme (140 kDa) was
      optimally active at 65  degrees C and pH 5.5, exhibited half life of 10 h at 60 
      degrees C, 78 and 88% residual activity after 24 h, at pH 4.5 and 8.0,
      respectively. Fe2+, Cu2+, Al3+, Ag+ and Hg2+ inhibited the enzyme; the activity
      was moderately stimulated by SDS and not influenced by beta-mercaptoethanol. In
      the presence of p-nitrophenyl-beta-d-xylopyranoside, AbXyl exhibited Km of 0.19
      mM, Kcat of 453.29 s-1, Kcat Km-1 of 2322 s-1 mM and was moderately influenced by
      xylose (Ki 21.25 mM). The enzyme hydrolyzed xylo-oligomers into xylose and
      catalyzed transxylosilation reactions also in presence of alcohols as acceptors,
      producing xylo-oligosaccharides and alkyl-xylosides. Finally AbXyl was applied
      towards a statistically optimized process of brewery's spent grain bioconversion,
      highlighting the important role of this biocatalyst in reaching high yields of
      fermentable sugars.

PMID- 30219518
TI  - Endothelium-specific CYP2J2 overexpression improves cardiac dysfunction by
      promoting angiogenesis via Jagged1/Notch1 signaling.
AB  - BACKGROUND: Myocardial infarction (MI) contributes to the development of cardiac
      remodeling and heart failure. Insufficient post-MI myocardial angiogenesis has
      been identified as a non-negligible event which precipitates heart failure
      progression. Previous studies reported that cytochrome P450 epoxygenase and its
      metabolites exerted beneficial effects on cardiovascular diseases. However, the
      role of cytochrome P450 2J2 (CYP2J2) in post-MI heart failure is incompletely
      understood. METHODS AND RESULTS: First, western blot and real-time PCR analyses
      showed that CYP2J2 expression increased clearly in patients with acute MI and old
      MI, compared to control. Second, echocardiography and histological studies showed
      that transgenic (TG) rats had relatively preserved cardiac function, as well as
      attenuated remodeling, and reduced scar formation, compared to the wild-type (WT)
      littermates after MI eight weeks. Importantly, the cardioprotective effect
      induced by CYP2J2 overexpression was abrogated by VEGFR2 inhibitor-cediranib.
      More intriguingly, positron emission computed Tomography (PET) analyses showed
      that TG rats displayed better myocardial perfusion than WT rats. We found that
      these effects were linked to increasing circulating EETs and enhancing myocardial
      angiogenesis. Additionally, in vitro study demonstrated that 11, 12
      epoxyeicosatrienoic acid (11, 12-EET) induced more robust tube formation and
      markedly increased VEGF-A and bFGF expression in hypoxia and normoxia. Finally,
      western blot analyses uncovered that CYP2J2 and 11, 12-EET promoted angiogenesis
      via the Jagged1/Notch1 signaling pathway. CONCLUSIONS: Our findings demonstrate
      that CYP2J2 improves cardiac function by increasing the concentration of
      circulating EETs, and boosting angiogenesis via the Jagged1/Notch1 signaling
      pathway in MI-induced heart failure.

PMID- 30219519
TI  - Ethyl 2,4-dicarboethoxy pantothenate, a derivative of pantothenic acid, prevents
      cellular damage initiated by environmental pollutants through Nrf2 activation.
AB  - BACKGROUND: Recently, environmental pollutants have become a concern not only for
      respiratory organs but also for skin-related human health, because skin is
      localized at the border between the human body and the external environment and
      is easily influenced by environmental pollutants. OBJECTIVE: Here, we
      investigated the effects of a novel pantothenic acid (PA) derivative, ethyl 2,4
      dicarboethoxy pantothenate (EDCEP), on a diesel particulate extract (DPE) as a
      representative environmental pollutant that generates reactive oxygen species
      (ROS) through the activation of aryl hydrocarbon receptor (AHR) signaling.
      METHODS: We characterized the effects of PA and EDCEP on normal human epidermal
      keratinocytes (NHEKs) exposed to DPE or H2O2 as a general oxidative stress
      stimulator. Cell viability and intracellular ROS levels were evaluated using the
      3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyltetrazolium bromide (MTT) assay and the
      2',7'-dichlorodihydrofluorescein diacetate (DCFDA) assay, respectively. Further,
      we investigated the substantial effects and the underlying mechanism of EDCEP,
      which elicited a reduction of intracellular ROS. RESULTS: PA and EDCEP restored
      the decreases of cell viability induced by DPE and also repressed the up
      regulation of CYP1A1 mRNA expression induced by DPE. Interestingly, the effects
      of PA and EDCEP on intracellular ROS levels showed different responses. EDCEP
      reduced intracellular ROS levels stimulated by DPE or by exposure to H2O2. EDCEP
      suppressed the secretion of tumor necrosis factor (TNF-alpha) and reduced the
      level carbonylated proteins in reconstructed human epidermal equivalents
      topically treated with DPE. EDCEP up-regulated the mRNA expression levels of
      nuclear factor E2-related factor 2 (Nrf2), gamma-glutamyl cysteine synthase
      (gamma-GCS), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1)
      and in addition, increased intracellular glutathione (GSH) levels. CONCLUSION:
      EDCEP reduces cellular damage initiated by environmental pollutants by
      stimulating the intracellular defense system against ROS through the activation
      of Nrf2, and by interfering with AHR signaling pathway activation.

PMID- 30219521
TI  - Efficacy of Videoconference Interviews in the Pediatric Surgery Match.
AB  - PURPOSE: The pediatric surgery match is highly competitive with the interview
      process requiring significant resources. The purpose of this study was to
      evaluate the efficacy of videoconference interviewing (VI) as a screening tool in
      the pediatric surgery match process. METHODS: During the 2017 interview season,
      applicants participated in VI prior to on-site interviews. Applicants and faculty
      completed 15 and 8-question surveys, respectively, regarding their experiences.
      RESULTS: Both faculty and applicants agreed VI was easily workable and allowed
      them to accurately represent themselves. Faculty agreed VI would change how they
      rank candidates and that it is a helpful screening tool. Most disagreed VI could
      substitute for on-site interviews. Most applicants reported the cost and time
      required for on-site interviews was a hardship. Overall, applicants moved an
      average of 5.5 +/- 2.9 (median 3) positions from the pre-VI to post-VI rank list.
      Thirty-seven percent of applicants moved out of the top ten rank list following
      VI. Of the lowest 5 applicants on the post-VI rank list, only 20% matched
      successfully. CONCLUSION: The pediatric surgery match requires a significant
      investment of time and money that creates a hardship for most applicants. VI may
      be an effective screening tool that could potentially reduce on-site interviews
      and alleviate the burden on applicants and general surgery training programs.

PMID- 30219520
TI  - The atopic dermatitis-like lesion and the associated MRSA infection and barrier
      dysfunction can be alleviated by 2,4-dimethoxy-6-methylbenzene-1,3-diol from
      Antrodia camphorata.
AB  - BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease with an
      associated barrier dysfunction and Staphylococcus aureus infection. The mainstay
      steroid and calcineurin inhibitor therapy shows some adverse effects. 2,4
      Dimethoxy-6-methylbenzene-1,3-diol (DMD) is a benzenoid isolated from Antrodia
      camphorata. OBJECTIVE: We investigated the inhibitory effect of DMD on
      methicillin-resistant S. aureus (MRSA), the chemokine production in stimulated
      keratinocytes, and the AD-like lesion found in ovalbumin (OVA)-sensitized mice.
      METHODS: The antimicrobial effect and cutaneous barrier function were evaluated
      using an in vitro culture model and an in vivo mouse model of AD-like skin.
      RESULTS: DMD exhibited a comparative minimum inhibitory concentration (MIC) and
      minimum bactericidal concentration (MBC) against MRSA with nalidixic acid, a
      conventional antibiotic. The MIC and MBC for DMD was 78.1 and 156.3 MUg/ml,
      respectively. DMD also showed the ability to eliminate the clinical bacteria
      isolates with resistance to methicillin and vancomycin. The DNA polymerase and
      gyrase inhibition evoked by DMD for bacterial lethality was proposed. In the
      activated keratinocytes, DMD stopped the upregulation of chemokines (CCL5 and
      CCL17) and increased the expression of differentiation proteins (filaggrin,
      involucrin, and integrin beta-1). Topical application of DMD facilely penetrated
      into the skin, with AD-like skin displaying 2.5-fold greater permeation than
      healthy skin. The in vivo assessment using the mouse model with OVA sensitization
      and MRSA inoculation revealed a reduction of transepidermal water loss (TEWL) and
      bacterial burden by DMD by about 2- and 100-fold, respectively. Differentiation
      proteins were also restored after topical DMD delivery. CONCLUSION: Our data
      demonstrated an advanced concept of AD treatment by combined barrier repair and
      bacterial eradication with a sole agent for ameliorating the overall
      complications.

PMID- 30219522
TI  - What Happens After a Stop the Bleed Class? The Contrast Between Theory and
      Practice.
AB  - OBJECTIVE: The Department of Homeland Security launched the Stop the Bleed
      initiative, a campaign intended to teach bystanders hemorrhage control
      strategies. Despite the program's popularity, little is known about actions taken
      by participants afterwards. We sought to determine how often participants
      acquired the equipment that is necessary in applying the skills taught. DESIGN: A
      standardized survey instrument was distributed to all American College of
      Surgeons Bleeding Control Basic (B-Con) class participants from 05/2017 to
      01/2018. The instrument queried about the likelihood of applying skills and
      obtaining materials. A web-based survey was administered one month later
      inquiring whether materials were obtained and barriers that would prohibit
      acquisition. SETTING: Academic, urban, Level I trauma center. PARTICIPANTS:
      Healthcare and nonhealthcare personnel. RESULTS: There were 336 and 183
      participants who completed the initial and subsequent web-based survey,
      respectively. Participants indicated a high likelihood of applying a tourniquet
      (95.5%), applying pressure (97.9%), and packing a wound (96.4%), if required.
      Additionally, 74.7% and 76.2% reported a high likelihood of obtaining a
      tourniquet and packing material, respectively. However, only 21.3% and 50.8%
      obtained a tourniquet and packing material, respectively, 1 month later. Cost,
      time, and accessibility of items during a time of need were cited to be common
      reasons for not obtaining these materials. CONCLUSIONS: Despite reporting a high
      likelihood of utilizing hemorrhage control skills upon completion of the B-Con
      class, few went on to acquire the materials needed to apply these skills among
      those who responded. These results may be impacted by loss of follow up and
      response bias. Developing strategies that allow for easy access to materials is
      imperative and may lead to both better implementation of the purposes of the
      program and improved dissemination of its principles within the community.

PMID- 30219523
TI  - Evaluating the primary stability of standard vs lateralised cementless femoral
      stems - A finite element study using a diverse patient cohort.
AB  - BACKGROUND: Restoring the original femoral offset is desirable for total hip
      replacements as it preserves the original muscle lever arm and soft tissue
      tensions. This can be achieved through lateralised stems, however, the effect of
      variation in the hip centre offset on the primary stability remains unclear.
      METHODS: Finite element analysis was used to compare the primary stability of
      lateralised and standard designs for a cementless femoral stem (Corail(r)) across
      a representative cohort of male and female femora (N = 31 femora; age from 50 to
      80 years old). Each femur model was implanted with three designs of the Corail(r)
      stem, each designed to achieve a different degree of lateralisation. An automated
      algorithm was used to select the size and position that achieve maximum
      metaphyseal fit for each of the designs. Joint contact and muscle forces
      simulating the peak forces during level gait and stair climbing were scaled to
      the body mass of each subject. FINDINGS: The study found that differences in
      restoring the native femoral offset introduce marginal differences in micromotion
      (differences in peak micromotion <21 MUm), for most cases. Nonetheless,
      significant reduction in the interfacial strains (>3000 MUepsilon) was achieved
      for some subjects when lateralized stems were used. INTERPRETATION: Findings of
      this study suggest that, with the appropriate size and alignment, the standard
      offset design is likely to be sufficient for primary stability, in most cases.
      Nonetheless, appropriate use of lateralised stems has the potential reduce the
      risk of peri-prosthetic bone damage. This highlights the importance of
      appropriate implant selection during the surgical planning stage.

PMID- 30219524
TI  - A Copper10-Paclitaxel crystal; a medicinally active drug delivery platform.
AB  - Paclitaxel is a well-known cancer drug that functions as a mitotic inhibitor.
      This work focuses on a copper based crystal that encapsulates the pharmaceutical
      agent and serves as a drug delivery agent. A Copper10-Pacitaxil1 chloride
      (CU10PAC1) complex is synthesized and tested against the National Cancer
      Institute's sixty cell line panel. The 10:1 ratio results in a crystal that was
      examined by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spec
      (MALDI-TOF-MS), Scanning Electron Microscopy (SEM) and Proton (1H) and Carbon
      (13C) Nuclear Magnetic Resonance (NMR). The potential attributes of a copper
      based crystal as an in vivo drug carrier for Paclitaxel are discussed.

PMID- 30219525
TI  - Antimicrobial 1,3,4-trisubstituted-1,2,3-triazolium salts.
AB  - A series of 1,3,4-trisubstituted-1,2,3-triazolium bromide salts were prepared by
      efficient two-step sequences of azide-alkyne cycloaddition and benzylic
      substitution. The antimicrobial activity of each triazolium salt and correlating
      triazole precursor was evaluated using a minimum inhibitory concentration (MIC)
      assay. MIC activities as low as 1 uM against Gram-positive bacteria, 8 uM against
      Gram-negative bacteria and 4 uM against fungi were observed for salt analogs,
      while neutral triazoles were inactive. Analogs representing selective and broad
      spectrum antimicrobial activity were each identified. MIC structure-activity
      relationships observed within this motif indicate that the presence of cationic
      charge and balance of overall hydrophobicity are strongly impactful, while benzyl
      vs. aryl substituent identity and variation of substituent regiochemistry are
      not.

PMID- 30219526
TI  - Antiplasmodial flavanones and a stilbene from Carpha glomerata.
AB  - Bioassay-guided fractionation of an extract of Carpha glomerata (Cyperaceae) led
      to the isolation of seven compounds. Compounds 1 (carphorin A), 3 (carphorin C),
      4 (carphorin D), and 5 (carphabene) are new compounds, and compound 2 (8-(3"
      hydroxyisoamyl)-naringenin) was isolated for the first time as a natural product.
      All structures were elucidated based on analyses of their HR-ESIMS and 1D and 2D
      NMR data. Compounds 1, 2, and 6, which have prenyl or hydroxyprenyl side chains,
      exhibited antiplasmodial activities with IC50 values of 5.2 +/- 0.6, 3.4 +/- 0.4,
      and 6.7 +/- 0.8 uM against the drug-resistant Dd2 strain of Plasmodium
      falciparum. In addition the prenylated stilbene 5 also showed good activity, with
      IC50 5.8 +/- 0.7 uM.

PMID- 30219527
TI  - Synthesis and antibacterial activity of novel 3-O-arylalkylcarbamoyl-3-O
      descladinosyl-9-O-(2-chlorobenzyl)oxime clarithromycin derivatives.
AB  - A novel series of 3-O-arylalkylcarbamoyl-3-O-descladinosyl-9-O-(2
      chlorobenzyl)oxime clarithromycin derivatives, were designed, synthesized and
      evaluated for their in vitro antibacterial activity. These derivatives were found
      to have strong activity against susceptible and resistant bacteria strains. Among
      them, compounds 7a and 7q showed the most potent activity (0.125 ug/mL) against
      erythromycin-resistant S. pneumoniae expressing the mefA gene. Moreover,
      compounds 7f, 7i, 7p and 7z displayed remarkably improved activity (4 ug/mL)
      against penicillin-resistant S. aureus ATCC31007, and compounds 7a, 7b, 7f, 7p
      and 7z showed improved activity (8 ug/mL) against erythromycin-resistant S.
      pyogenes. In particular, compound 7z exhibited potent and balanced activity
      against the tested drug-susceptible and -resistant bacterial strains.

PMID- 30219528
TI  - Engineering NADH/NAD+ ratio in Halomonas bluephagenesis for enhanced production
      of polyhydroxyalkanoates (PHA).
AB  - Halomonas bluephagenesis has been developed as a platform strain for the next
      generation industrial biotechnology (NGIB) with advantages of resistances to
      microbial contamination and high cell density growth (HCD), especially for
      production of polyhydroxyalkanoates (PHA) including poly(3-hydroxybutyrate)
      (PHB), poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) and poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). However, little is known about the
      mechanism behind PHA accumulation under oxygen limitation. This study for the
      first time found that H. bluephagenesis utilizes NADH instead of NADPH as a
      cofactor for PHB production, thus revealing the rare situation of enhanced PHA
      accumulation under oxygen limitation. To increase NADH/NAD+ ratio for enhanced
      PHA accumulation under oxygen limitation, an electron transport pathway
      containing electron transfer flavoprotein subunits alpha and beta encoded by etf
      operon was blocked to increase NADH supply, leading to 90% PHB accumulation in
      the cell dry weight (CDW) of H. bluephagenesis compared with 84% by the wild
      type. Acetic acid, a cost-effective carbon source, was used together with glucose
      to balance the redox state and reduce inhibition on pyruvate metabolism,
      resulting in 22% more CDW and 94% PHB accumulation. The cellular redox state
      changes induced by the addition of acetic acid increased 3HV ratio in its
      copolymer PHBV from 4% to 8%, 4HB in its copolymer P34HB from 8% to 12%,
      respectively, by engineered H. bluephagenesis. The strategy of systematically
      modulation on the redox potential of H. bluephagenesis led to enhanced PHA
      accumulation and controllable monomer ratios in PHA copolymers under oxygen
      limitation, reducing energy consumption and scale-up complexity.

PMID- 30219529
TI  - Detoxification and simultaneous removal of phenolic xenobiotics and heavy metals
      with endocrine-disrupting activity by the non-ligninolytic fungus Umbelopsis
      isabellina.
AB  - Organic and inorganic pollutants well known to interfere with the major functions
      of the endocrine system co-occur widely in contaminated ecosystems. The aim of
      the study was to evaluate the ability of Umbelopsis isabellina fungus to
      simultaneously remove and detoxify multiple environmentally significant endocrine
      disruptors: the heavy metals Cd(II), Zn(II), Mn(II), Pb(II) and Ni(II) and the
      phenolic xenobiotics nonylphenol (t-NP), 4-cumylphenol (CP) and 4-tert
      octylphenol (4-t-OP). The effects of the metals on fungal growth and efficiency
      of single-metal uptake were also investigated. U. isabellina exhibited
      considerable tolerance to Zn(II), Mn(II), Pb(II) and Ni(II), with IC50/24 values
      ranging from 5.08 for Ni(II) to 13.1 mM for Zn(II). In the presence of CP, the
      maximum efficiency of Pb(II) removal increased 25% relative to that of the
      control. Supplementation with Mn(II) or Zn(II) enhanced the 4-t-OP degradation by
      18 or 9%, respectively, after 6 h of cultivation. Ecotoxicological assays
      monitoring bioindicators from different aquatic ecosystems revealed
      detoxification coinciding with the removal of metals and organic xenobiotics from
      binary mixtures. This work indicates the potential of a single microorganism, U.
      isabellina, to remove both heavy metals and organic xenobiotics from co
      contaminated sites, making it a suitable candidate for the development of
      bioremediation strategies.

PMID- 30219530
TI  - Critically ill neonates with coarctation of the aorta: Building bridges to the
      future.

PMID- 30219531
TI  - Red cell distribution width in congenital heart disease patients: Beyond
      cardiovascular events.

PMID- 30219532
TI  - Author's reply: Atrial fibrillation and sleep apnea: A chicken and egg situation.

PMID- 30219533
TI  - Success predictor of cryoballoon ablation in atrial fibrillation: Left atrial
      volume vs area.

PMID- 30219535
TI  - Low diastolic blood pressure for HFpEF.

PMID- 30219534
TI  - New-onset atrial fibrillation in ICU: A FROG in the throat.

PMID- 30219536
TI  - Facts and details: Ivabradine in acute decompensated heart failure.

PMID- 30219538
TI  - Development of Takotsubo syndrome and cancer may share a common signaling
      pathway.

PMID- 30219537
TI  - Low diastolic blood pressure and adverse outcomes in older patients with
      hypertension.

PMID- 30219539
TI  - Gout and CV disease: It is time to move on.

PMID- 30219540
TI  - Increased risk of myocardial infarction with dabigatran etexilate: Fact or
      fiction? A critical meta-analysis from integrating randomized controlled trials
      and real-world studies: Wine or spritzer?

PMID- 30219542
TI  - Survival after bilateral internal mammary artery in coronary artery bypass
      grafting: Are women at risk?
AB  - BACKGROUND: Most observational studies support long-term survival benefit after
      bilateral internal mammary artery (BIMA) compared with single internal mammary
      artery (SIMA) coronary artery bypass grafting (CABG) but data on females is
      scarce. We compared survival and safety of BIMA versus SIMA CABG between males
      and females at our tertiary care center. METHODS: Single-center retrospective
      cohort including consecutive patients with at least 2 left-coronary system (LCS)
      vessel disease who underwent isolated CABG with at least 1 IMA conduit and a
      minimum of 2 conduits targeting the LCS in 2004-2013. All-cause mortality was the
      primary outcome, secondary outcomes were early mortality and reoperation due to
      sternal wound complications (SWC). Kaplan-Meier analysis after inverse
      probability weighting using propensity score (IPW) was used to compare BIMA and
      SIMA CABG amongst genders. Results were confirmed in subgroup analysis. RESULTS:
      BIMA CABG was performed in 39% out of 2424 eligible procedures and in 27% of 460
      females. No differences were found in survival after BIMA and SIMA CABG (median
      and maximum follow-up of 5.5 and 12 years, respectively) but a statistical
      interaction was observed with gender (P < 0.001). Females who underwent BIMA CABG
      showed higher mortality (weighted HR in females subset: 3.16; 95% CI: 1.56-6.29,
      P = 0.001). BIMA CABG showed a higher incidence of reoperation due to SWC (IPW
      adjusted model OR: 1.74; 95% CI: 1.16-2.60) that was mostly ascribable to males
      (weighted OR in males: 3.10; 95% CI: 1.74-5.51, P < 0.001). CONCLUSIONS: Females
      may experience higher mortality after BIMA CABG which should be further explored.

PMID- 30219541
TI  - Cytokines profile of reverse cardiac remodeling following transcatheter aortic
      valve replacement.
AB  - OBJECTIVE: Previous studies have suggested that cytokines and growth factors may
      predict ventricular recovery following aortic valve replacement (AVR). The
      primary objective of this study was to identify cytokines that predict
      ventricular recovery following transcatheter AVR (TAVR). METHODS: We
      prospectively enrolled 121 consecutive patients who underwent TAVR. Standard
      echocardiographic assessment at baseline, 1-month and 1-year after TAVR included
      left ventricular (LV) mass index (LVMI) and global longitudinal strain (GLS).
      Blood samples were obtained at the time of the procedure to measure cytokines
      using a 63-plex Luminex platform. Partial least squares-discriminant analysis was
      performed to identify cytokines associated with ventricular remodeling and
      function at baseline as well as 1 year after TAVR. RESULTS: The mean age was 84
      +/- 9 years, with a majority of male subjects (59%), a mean LVMI of 120.4 +/-
      45.1 g/m2 and LVGLS of -13.0 +/- 3.2%. On average, LV mass decreased by 8.1% and
      GLS improved by 20.3% at 1 year following TAVR. Among cytokines assayed, elevated
      hepatocyte growth factor (HGF) emerged as a common factor significantly
      associated with worse baseline LVMI and GLS as well as reduced ventricular
      recovery (p < 0.005). Other factors associated with ventricular recovery included
      a select group of vascular growth factors, inflammatory mediators and tumor
      necrosis factors, including VEGF-D, ICAM-1, TNFbeta, and IL1beta. CONCLUSION: We
      identified a network of cytokines, including HGF, that are significantly
      correlated with baseline LVMI and GLS, and ventricular recovery following TAVR.

PMID- 30219543
TI  - Lessons Learned: A Roundtable Discussion on Succeeding in Cardiothoracic Surgical
      Residency and Practice.

PMID- 30219544
TI  - #vatslobectomy.

PMID- 30219545
TI  - Characteristics of lingual papillae in diabetic rats.
AB  - Diabetes mellitus (DM) is a metabolic disorder resulting with many different
      complications including soft tissue abnormalities in the oral cavity such as
      periodontitis and salivary and taste dysfunction. Previous studies also reported
      fungal and bacterial infections in oral cavity in these patients. This study aims
      to represent three dimentional morphologic ultrastructural changes of the
      diabetic rat tongue via scanning electron microscopy. Twenty-four (24) adult male
      Spraque-Dawley rats, (weight ranging between 200-250g) included in the study were
      randomly assigned into two groups: control rats were injected with
      intraperitoneally saline alone, experimental diabetes group received
      streptozotocin (STZ) (80mg/kg) administrated intraperitoneally. On month four, by
      the end of experimental period, all animals of each group were anesthetised. All
      tongues were dissected totally, postfixed in 2% osmium tetroxide and then dried
      by critical point drying before SEM analysis. Finally, superficial epithelial
      configurations of the lingual papillae in experimental diabetic rats were
      examined by scanning electron microscopy. Diabetes mellitus caused thickness,
      hyperceratosis and different epithelial changes, We observed yeast-like
      structures and bacterial colonisations on the papillar and epithelial structure
      of the tongue. The morphological atrophic changes of lingual mucosa and the
      median rhomboid glossitis (which is primary finding of candidal infection) are
      characteristic observations on the lingual mucosa of the streptozotocin treated
      rats.

PMID- 30219546
TI  - Information Processing and Distributed Computation in Plant Organs.
AB  - The molecular networks plant cells evolved to tune their development in response
      to the environment are becoming increasingly well understood. Much less is known
      about how these programs function in the multicellular context of organs and the
      impact this spatial embedding has on emergent decision-making. Here I address
      these questions and investigate whether the computational control principles
      identified in engineered information processing systems also apply to plant
      development. Examples of distributed computing underlying plant development are
      presented and support the presence of shared mechanisms of information processing
      across these domains. The coinvestigation of computation across plant biology and
      computer science can provide novel insight into the principles of plant
      development and suggest novel algorithms for use in distributed computing.

PMID- 30219547
TI  - Editor's Page.

PMID- 30219548
TI  - 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the
      Prevention, Detection, Evaluation, and Management of High Blood Pressure in
      Adults: Executive Summary: A Report of the American College of
      Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

PMID- 30219549
TI  - Very Early Diuretic Response After Admission for Acute Heart Failure.
AB  - BACKGROUND: In hospitalized heart failure patients, a poor diuretic response (DR)
      during the first days of hospital admission is associated with worse outcomes.
      However, it remains unknown whether DR in the first hours has similar prognostic
      value. Moreover, data on the sequential change in DR during hospital admission
      are lacking. METHODS AND RESULTS: DR (urine output per 40-mg furosemide
      equivalent diuretics dose) was measured from 0 to 6 hours (DR6), 6 to 48 hours
      (DR6-48), and 0 to 48 hours (DR48) of the patient's emergency department (ED)
      arrival in 1551 patients with acute heart failure (AHF; mean age 78 years, 56%
      male, and 48% de novo patients with heart failure). Patients with a poor DR
      within the first 6 hours were older age, had worse renal function, and were
      already on diuretic treatment before admission. DR6 was only weakly correlated
      with DR6-48 (Spearman's rho = 0.273; P < .001). DR6, DR6-48, and DR48 were all
      significantly associated with 60-day mortality independent of other prognostic
      factors. DR6 and DR48 showed comparable prognostic ability. However, the model
      combining DR6 with DR6-48 significantly exceeded both DR6 (net reclassification
      improvement 0.249; P = .032) and DR48 (net reclassification improvement 0.287; P
      = 0.025) with regard to 60-day mortality prediction. CONCLUSIONS: DR measured
      within the first 6 hours of ED arrival and DR measured during the first 48 hours
      in patients with AHF have similar prognostic value, although they were moderately
      correlated. Changes in DR over time provide additional prognostic information.

PMID- 30219550
TI  - Lower Extremity Function Is Independently Associated With Hospitalization Burden
      in Heart Failure With Preserved Ejection Fraction.
AB  - BACKGROUND: Frailty reflects decreased resilience to physiological stressors; its
      prevalence and prognosis are not fully defined in heart failure with preserved
      ejection fraction (HFpEF). METHODS: The Short Physical Performance Battery (SPPB)
      was prospectively obtained in 114 outpatients with HFpEF. The SPPB tests gait
      speed, tandem balance, and timed chair rises, each scored from 0 to 4 points.
      Severe and mild frailty were respectively defined as an SPPB score <=6 and 7-9
      points. We used risk-adjusted logistic, Poisson, and negative binominal
      regression, respectively, to assess the relationship between SPPB score and risk
      of death or all-cause hospitalization, number of hospitalizations, and days
      hospitalized or dead longer than 6 months. RESULTS: Patients were similar to
      other HFpEF cohorts (age 68 +/- 13 years, 58% female, body mass index 36 +/- 8
      kg/m2, multiple comorbidities). Mean SPPB score was 6.9 +/- 3.2, and 80% of
      patients were at least mildly frail. Over a 6-month period, the SPPB score
      independently predicted death or all-cause hospitalization (odds ratio 0.81 per
      point, 95% confidence interval [CI] 0.69-0.94, P = .006), number of
      hospitalizations (incidence rate ratio 0.92 per point, 95% CI 0.86-0.97, P =
      .006), and days hospitalized or dead (incidence rate ratio 0.85 per point, 95% CI
      0.73-0.99, P = .04). CONCLUSIONS: Lower extremity function, as measured by the
      SPPB, independently predicts hospitalization burden in outpatients with HFpEF.
      Additional studies are warranted to explore shared mechanisms and treatment
      implications of frailty in HFpEF.

PMID- 30219551
TI  - Electronic clinical reminder and quality of primary diabetes care.
AB  - AIMS: To study the association of EMR's clinical reminder use on a comprehensive
      set of diabetes quality metrics in U.S. office-based physicians and within solo-
      versus multi-physician practices. We conducted a retrospective cohort study on
      visits made by adults with diabetes identified from the National Ambulatory
      Medical Care Survey (2012-2014). METHODS: Multiple logistic regression is used to
      test for associations between clinical reminder use and recommended services by
      the American Diabetes Association. RESULTS: Of 5508 visits, nationally
      representing 112,978,791 visits, 31% received HbA1c tests, 13% received
      urinalysis test, and <10% received retinal or foot exams. Main effects of
      practice size and clinical reminder use were found for HbA1c, urinalysis, and
      foot exams. We find no statistically significant relationship to suggest that
      clinical reminder use improve diabetes process guidelines for solo practices.
      CONCLUSIONS: Resource efforts, beyond clinical reminders, are needed to reduce
      gaps in primary diabetes care between solo and non-solo practices.

PMID- 30219552
TI  - Can Gartland II and III supracondylar humerus fractures be treated using Blount's
      method in the emergency room?
AB  - BACKGROUND: Studies have established that Blount's method is reliable for
      treating extension supracondylar fractures (SCFs) in paediatric patients.
      Reduction in the emergency room (ER) under procedural sedation followed by
      orthopaedic treatment is increasingly used for many fracture types. The primary
      objective of this study was to determine whether SCF reduction in the ER was
      feasible, by determining the failure rate. The secondary objective was to
      identify causes of failure with the goal of improving patient selection to
      reduction in the ER. HYPOTHESIS: Gartland II and III SCFs (Lagrange-Rigault
      grades 2-4) can be treated in the emergency room under fluoroscopic guidance and
      with procedural sedation. MATERIAL AND METHODS: A retrospective study was
      conducted in 128 paediatric patients who underwent ER reduction of an SCF in 2014
      2015. Mean age was 5.6 years. Reduction was performed either by an orthopaedic
      surgery resident or by a specially trained emergency physician. RESULTS: Of the
      128 SCFs, 101 (79%) were Gartland II and 27 Gartland III. In the Lagrange-Rigault
      classification, 55 (43%) fractures were grade 2, 59 (46%) were grade 3, and 14
      (11%) were grade 4. The arm was immobilised using the cuff-and-collar method
      described by Blount for 4 weeks. All 128 fractures healed without delay. Blount's
      method alone was effective in 112 (87.5%) patients. Of the 16 other patients, 15
      (Lagrange-Rigault 3, n=14; and 4, n=1) had an unstable fracture after ER
      reduction and were managed by reduction and internal fixation in the operating
      room. The remaining patient (0.5%) experienced secondary displacement requiring
      revision surgery in the operating room. CONCLUSION: SCFs grades 2 to 4 in the
      Lagrange-Rigault classification (Gartland II and III) can be treated in the ER by
      specially trained physicians. Lagrange-Rigault grade 3/Gartland III SCFs are more
      likely to require subsequent internal fixation but do not contraindicate
      reduction in the ER. LEVEL OF EVIDENCE: IV, retrospective study.

PMID- 30219553
TI  - Does Mechanical Bowel Preparation Reduce the Risk of Developing Infectious
      Complications in Pediatric Colorectal Surgery? A Systematic Review and Meta
      Analysis.
AB  - OBJECTIVES: To evaluate whether the application of mechanical bowel preparation
      (MBP) before colorectal surgery reduces the risk of developing infectious
      complications in children. STUDY DESIGN: In this systematic review and meta
      analysis, PubMed, Embase, and the Cochrane Library were systematically searched
      to identify all articles comparing pediatric patients receiving MBP with
      pediatric patients not receiving MBP before colorectal surgery. Results are
      presented with weighted risk differences based on the number of events and sample
      size per study. RESULTS: Six original studies were included comparing MBP (n =
      810) and no MBP (n = 1167). The overall risk of developing infectious
      complications was 10.1% in patients with MBP, compared with 9.1% in patients
      without MBP, resulting in a nonsignificant risk difference of -0.03% (95% CI, 
      0.09% to 0.03%). Concerning the number of wound infections and anastomotic leaks,
      we found nonsignificant risk differences of -0.03% (95% CI, -0.08% to 0.02%) and
      0.01% (95% CI, -0.01% to 0.02%), respectively. CONCLUSION: Based on the current
      literature, there is insufficient evidence to indicate that the use of MBP leads
      to a significant difference in the risk of developing infectious complications in
      pediatric colorectal surgery.

PMID- 30219554
TI  - Prevalence and risk factors for IgG antibodies to Neospora spp. in three types of
      equids from Southern Punjab, Pakistan.
AB  - Equine hosts suffer from neurological disease, congenital infection, and
      reproductive problems associated with Neospora spp. infection. We conducted a
      cross sectional study using sera from 631 equids (324 horses, 218 donkeys and 89
      mules) from the southern region of Punjab province, Pakistan to determine the
      prevalence of antibodies against Neospora spp. in this diverse group of equines.
      Fisk factors associated with seropositivity were evaluated statistically based on
      equine type, breed, age, husbandry, breeding methods, and reproductive history.
      Prevalence of antibodies to Neospora spp. was detected using a commercially
      available competitive ELISA kit. We detected IgG antibodies to Neospora spp. in
      23.3% of the equids with prevalence by host being 16.0% in horses, 32.6% in
      donkeys and 26.9% in 89 mules. Statistically significant (P < 0.05) differences
      in prevalence were observed among these hosts. Prevalence ranged in breeds of
      horses from 3.7% in the Morna breed, 12.4% in breeding stock, 26.8% in draughting
      stock, to 31.4% in unknown breeds. No significant (P > 0.05) difference in
      prevalence was noted among age groups. Prevalence was significantly (P < 0.05)
      higher in female equines with a history of abortion than those with no history of
      abortion. This is the first report documenting Neospora spp. in equines from
      Pakistan and it provides evidence that Neospora spp. is associated with abortions
      in female equines in Pakistan.

PMID- 30219555
TI  - Coxiella burnetii in Tunisian dromedary camels (Camelus dromedarius):
      Seroprevalence, associated risk factors and seasonal dynamics.
AB  - Q fever, caused by Coxiella burnetii, is a zoonotic disease responsible of
      abortion in ruminants. Few studies have investigated the prevalence of this
      infection in camels (Camelus dromedarius). The present report aimed to highlight
      the epidemiological status and identify the risk factors associated with C.
      burnetii infection in one-humped dromedary that is the most productive livestock
      species in arid areas. A total of 534 sera of healthy camels were collected in
      eight governorates from southern and central Tunisia. Samples were tested by an
      indirect Enzyme linked Immunosorbent Assay (ELISA). Results were analyzed using
      the Chi-square test and logistic regression. Overall, 237 camels (44%, 95%CI:
      0.40-0.49) were seropositive to C. burnetii. Statistical analysis pointed out
      four potential risk factors associated with infection. A meaningful high
      seropositivity was observed in female camels with a previous history of abortion
      (70%) (OR = 4.186, 95%CI: 2.05-8.51). Seroprevalence was higher in aged camels
      (>10 years-old) (48%) (OR = 2.91, 95%CI: 1.37-6.17). Besides, camels, intended
      for meat production from small herds showed a high level of infection (52%) (OR =
      2.43, 95%CI: 1.3-4.5). Coxiellosis evolved in dromedary herds throughout the
      year, however infection was significantly important in autumn (60%) (OR = 4.13,
      95%CI: 1.86-9.17) and winter (56%) (OR = 5.52, 95%CI: 2.50-12.16). Bioclimatic
      stage, gender, tick infestation and contact with other ruminants were not risk
      factors in camel's infection by C. burnetii. Our reports confirm that Tunisian
      one-humped dromedaries had been exposed to this bacterium and could contribute to
      its dissemination among farmers and other livestock animals. Furthers studies are
      required to evaluate the prevalence of Q fever among people professionally
      exposed like farmers, veterinarians and slaughterhouse workers.

PMID- 30219556
TI  - "Utilization of BCG for Non-Muscle Invasive Bladder Cancer in an Era of BCG
      Supply Shortages".
AB  - OBJECTIVES: To study trends in Bacillus Calmette-Guerin (BCG) utilization for non
      muscle invasive bladder cancer (NMIBC) before and during national BCG shortages.
      METHODS: The National Cancer Database was used to identify patients with
      localized NMIBC. Multivariate logistic regression was used to assess factors
      associated with BCG use. Temporal trends in BCG use were studied using segmented
      regression analysis. RESULTS: We identified 238,279 patients with NMIBC from 2004
      2015. Overall, 33,660 (14.1%) patients with NMIBC received intravesical BCG
      during the study period. Segmented regression revealed a slower rate of rise of
      BCG utilization following major supply interruptions in 2011 and 2012 (2004-2012:
      +0.62% increase per year [p<.0001]; 2013-2015: +0.29% increase per year
      [p=0.084]). This trend was most pronounced in Ta-low grade patients and least
      pronounced in T1-high grade patients. CONCLUSIONS: BCG utilization for NMIBC
      increased significantly over the study period, possibly representing increased
      adoption of national guidelines for BCG in NMIBC. In the years following
      interruptions in BCG supply, BCG use appears to have been rationed based on
      clinical risk, with the steepest declines in BCG use occurring in the lowest risk
      patients.

PMID- 30219557
TI  - A Rare Case of Triplicate Ureter.
AB  - Ureter triplication is an extremely rare congenital anomaly of the urinary system
      with approximately 100 cases reported in medical literature, since it was first
      described in 1870. It is classified into 4 types, and commonly associated with
      ipsilateral or contralateral urological anomalies. In this report, we present a
      case of a pediatric Type III-triplicate ureter associated with ipsilateral
      vesicoureteral reflux and contralateral idiopathic renal atrophy that was
      discovered during kidney transplant work-up. Diagnosis was made using multislice
      computed tomography and was confirmed intra-operatively.

PMID- 30219558
TI  - Modified Nephrometry Score With Body Mass Index More Accurately Predicts Ischemic
      Time in Transabdominal Laparoscopic Partial Nephrectomy for Small Renal Masses.
AB  - OBJECTIVE: To accurately predict the ischemic time (IT) and select candidates for
      transabdominal laparoscopic partial nephrectomy (LPN). METHODS: Transabdominal
      LPN was performed for 135 Japanese patients with renal masses <7cm in diameter
      between 2009 and 2016 by a single surgeon in a single institute. The renal
      parenchymal sutures were done with a combination of felt, Hem-o-lok and Lapra-Ty.
      The original R.E.N.A.L. nephreometry score (NS) was modified as follows. In terms
      of the tumor size (R), 1, 2, and 3 points were given for <=2.5, 2.5-4, and >4cm,
      respectively. For tumor location (A), 1, 2, and 3 points were given for anterior,
      on the coronal plane, and posterior, respectively. RESULTS: The median IT was
      24.6 minutes. Using the original NS, 64, 65, and 6 patients were categorized into
      low (4-6), moderate (7-9), and high (10-12) complexity, respectively. With the
      modified NS, 42, 75, and 18 patients were categorized into low (5-7), moderate (8
      11), and high (12-15) complexity, respectively. Pearson's correlation coefficient
      (R) between the original NS and IT was 0.297, whereas the R was improved to 0.388
      when the modified NS was employed. If the modified NS was low complexity, 95.2%
      achieved IT <30 minutes. Of them, none showed IT >=30 minutes if the body mass
      index was <25 kg/m2. CONCLUSION: The modified NS had a better correlation to the
      IT than the original NS for patients with tumor sizes <7cm who underwent
      transabdominal LPN. The modified NS with body mass index is a practical tool to
      select candidates for transabdominal LPN.

PMID- 30219559
TI  - The Impact of Chronic Pelvic Ischemia on LUTS and Urinary Levels of
      Neuroinflammatory, Inflammatory, and Oxidative Stress Markers in Elderly Men: A
      Case-control Study.
AB  - OBJECTIVE: To investigate lower urinary tract symptoms (LUTS) and urinary levels
      of neuroinflammatory, inflammatory, and oxidative stress markers in elderly men
      with chronic pelvic ischemia (CPI) caused by significant aortoiliac disease.
      MATERIALS AND METHODS: Thirteen men aged over 60 years, with aorta, unilateral or
      bilateral common/internal iliac artery occlusion documented by computed
      tomography angiography or angiography, were enrolled from the vascular surgery
      department. Twelve sex- and age-matched controls without significant aortoiliac
      disease were used for comparison. Exclusion criteria included neurogenic bladder
      dysfunction, bladder or prostate cancer, prostatic surgery, pelvic radiotherapy,
      or chronic treatment for LUTS. Participants underwent urological examination,
      including assessment of International Prostate Symptom Score (IPSS),
      uroflowmetry, postvoid residual (PVR), and prostate volume. Urine samples were
      collected, and levels of neuroinflammatory (nerve growth factor, NGF),
      inflammatory (cytokines), and oxidative stress markers (8-hydroxy-2'
      deoxyguanosine) were determined by enzyme-linked immunosorbent assay. RESULTS:
      Groups were similar for age, PVR, prostate volume, and most cardiovascular risk
      factors. IPSS was higher in patients with CPI (11 +/- 3 vs 8 +/- 2, P = .02),
      with a significant mean difference between groups of three points. Urinary NGF
      was significantly higher in men with CPI (3.7 +/- 0.8 vs 2.9 +/- 0.7, P = .02),
      but no differences were found in inflammatory and oxidative biomarkers among
      groups. CONCLUSION: Severe CPI in elderly men is associated with a significant
      increase in LUTS and bladder neurogenic inflammation, as suggested by the
      increase of NGF release in urine, sensitizing bladder afferents. These findings
      confirm the relevance of ischemia in bladder function and appear to validate
      animal models of bilateral iliac artery occlusion.

PMID- 30219560
TI  - Electrophysiological predictors of cognitive-behavioral therapy outcome in tic
      disorders.
AB  - Cognitive-behavioral therapy (CBT) constitutes an empirically based treatment for
      tic disorders (TD), but much remains to be learned about its impact at the neural
      level. Therefore, we examined the electrophysiological correlates of CBT in TD
      patients, and we evaluated the utility of event-related potentials (ERP) as
      predictors of CBT outcome. ERPs were recorded during a stimulus-response
      compatibility (SRC) task in 26 TD patients and 26 healthy controls. Recordings
      were performed twice, before and after CBT in TD patients, and with a similar
      time interval in healthy controls. The stimulus- and response-locked lateralized
      readiness potentials (sLRP & rLRP) were assessed, as well as the N200 and the
      P300. The results revealed that before CBT, TD patients showed a delayed sLRP
      onset and larger amplitude of both the sLRP and rLRP peaks, in comparison with
      healthy controls. The CBT induced an acceleration of the sLRP onset and a
      reduction of the rLRP peak amplitude. Compared to healthy controls, TD patients
      showed a more frontal distribution of the No-Go P300, which was however not
      affected by CBT. Finally, a multiple linear regression analysis including the
      N200 and the incompatible sLRP onset corroborated a predictive model of
      therapeutic outcome, which explained 43% of the variance in tic reduction
      following CBT. The current study provided evidence that CBT can selectively
      normalize motor processes relative to stimulus-response compatibility in TD
      patients. Also, ERPs can predict the amount of tic symptoms improvement induced
      by the CBT and might therefore improve treatment modality allocation among TD
      patients.

PMID- 30219561
TI  - The effect of exercise on resting concentrations of peripheral brain-derived
      neurotrophic factor (BDNF) in major depressive disorder: A meta-analysis.
AB  - Exercise interventions have been shown to successfully improve depression in
      patients with major depressive disorder (MDD), but like other forms of
      antidepressant treatment, exercise is not effective in all patients and its
      mechanisms of action have not been fully elucidated. Brain-derived neurotrophic
      factor (BDNF), a key mediator of neurogenesis and neuronal survival, has been
      shown to be decreased in individuals with MDD. One potential mechanism by which
      exercise alleviates depression is through an increase in BDNF. In order to
      evaluate this hypothesis, we conducted a meta-analysis of studies that assessed
      the effects of a chronic (multi-week) exercise intervention on BDNF
      concentrations in MDD patients. MEDLINE, Embase, PsycINFO, SPORTDiscus,
      Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for
      original, peer-reviewed reports of peripheral blood BDNF concentrations before
      and after a chronic exercise intervention in MDD patients. Standardized mean
      differences (SMDs) were generated from random effects models. Potential sources
      of heterogeneity were explored in meta-regression analyses. In six studies that
      met inclusion criteria, resting blood concentrations of BDNF were not
      significantly higher after a chronic exercise intervention (SMD = 0.43, 95% CI: 
      0.06-0.92, p = 0.09) in MDD patients. This meta-analysis did not find evidence
      that a chronic aerobic exercise intervention increases resting concentrations of
      BDNF in the blood of MDD patients; however, there is a lack of studies in this
      area making it difficult to reach a definitive conclusion. Future studies on this
      topic with larger sample sizes and longer durations are needed to draw more
      robust conclusions.

PMID- 30219562
TI  - Clinical outcome of maintenance electroconvulsive therapy in comorbid
      Posttraumatic Stress Disorder and major depressive disorder.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) and major depressive disorder
      (MDD) are prevalent and frequently comorbid. Approximately 42-48% of patients
      with PTSD also meet diagnostic criteria for MDD. Maintenance electroconvulsive
      therapy (mECT) has been found to be efficacious for the prevention of recurrence
      of MDD. This study investigated the efficacy of mECT in the treatment of MDD with
      and without comorbid syndromal PTSD. METHODS: This retrospective study includes
      36 patients, 26 with MDD and 10 with comorbid MDD & PTSD receiving monthly mECT
      for a mean of 1.5 years. The mean age was 52 +/- 14 years and 25% were female.
      The change in PTSD and MDD symptoms in response to mECT was assessed using
      Clinical Global Impression - Severity Scale (CGI-S). Heart rate variability
      (HRV), 12-month hospitalization rate, suicide rate and all-cause mortality in
      response to mECT were assessed and compared between groups using repeated
      generalized linear regression (GLM) analysis. RESULTS: At mECT baseline, there
      were no statistically significant differences in CGI-S scores, HRV between
      patients with MDD alone and those with comorbid MDD and PTSD (P > 0.05). After 12
      months of mECT, a significant increase in HRV (mean difference: 10.9 95%CI 4.8
      20.3, p = 0.001) and decrease in CGI-S overall (mean difference: 3.5, 95% CI 3.3
      3.6, p = 0.001)], PTSD (mean difference: 3.4, 95% CI 3.2-3.6, p = 0.001)], and
      MDD (mean difference: 3.8, 95% CI 3.5-3.9, p = 0.001)] symptoms in both groups
      were noted (p < 0.05). No psychiatric hospitalization or suicide occurred in any
      of the patients. CONCLUSIONS: Maintenance ECT is associated with improved HRV,
      reduction of both major depression and PTSD symptoms, and a favorable clinical
      outcome.

PMID- 30219563
TI  - Cerebrospinal fluid monoamine metabolite concentrations in depressive disorder: A
      meta-analysis of historic evidence.
AB  - Altered monoaminergic functions have been implicated in the pathophysiology of
      depressive disorder. However, previously reported cerebrospinal fluid (CSF)
      monoamine metabolite concentrations in major depression have been inconsistent.
      We performed a meta-analysis of historic evidence to determine whether CSF
      monoamine metabolite levels were different between patients with depression and
      normal controls, and could be used as depression biomarkers. Relevant studies
      that investigated CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid
      (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in patients with
      depression and normal controls were identified in PubMed, Web of Science,
      PsycINFO, and Embase databases through September 5, 2017, using a synonymous
      search for depression, CSF, normal, control, and each monoamine metabolite name,
      and in the reference lists of the acquired articles. Obtained records were
      individually scrutinized for eligibility. Our search strategy identified 26
      studies, including our own. We employed random effects modeling and adopted
      "Hedges's g" as an index of effect size. In the meta-analyses, no significant
      difference was observed in CSF 5-HIAA or MHPG levels between patients with
      depressive disorder and controls. In contrast, CSF HVA was significantly
      decreased in patients with depression (Hedges's g = -0.30, P = 0.0000025), and
      these results remained significant after patients with bipolar disorder were
      excluded (Hedges's g = -0.37, P = 0.000061). In the meta-regression, sex was
      significantly associated with the Hedges's g of CSF HVA (Q = 4.41, P = 0.036).
      This meta-analysis revealed that only CSF HVA, and not 5-HIAA or MHPG, levels
      were decreased in depressive disorder. The reduction in the CSF HVA concentration
      in patients with depression may guide future studies on depression and serve as a
      useful biomarker of depressive disorder.

PMID- 30219564
TI  - Living in fear: Low-cost avoidance maintains low-level threat.
AB  - BACKGROUND AND OBJECTIVES: Excessive avoidance of potential threat is a hallmark
      of anxiety and is thought to maintain fear by preserving the perceived high
      threat value of avoided situations. Previous research has shown that the
      availability of avoidance maintains low-level threat. Here, we investigated
      whether an opportunity to engage in avoidance in the presence of a low-threat
      value safety cue would maintain its perceived threat value when avoidance was
      unavailable. METHODS: In a threat conditioning procedure, one conditional danger
      stimulus (CS+; A+) was followed by an aversive unconditioned stimulus (US;
      electric shock), and two safety stimuli (CS-; B- and C-) were never followed by
      the US. Next, clicking a button present during A+ avoided the scheduled US.
      Avoidance was then made available during C- for participants in the Experimental
      group but not in the Control group. In the test, all stimuli were presented
      without the opportunity to avoid. Threat expectancy, eyeblink startle
      electromyography (EMG), and skin conductance responses (SCRs) were measured.
      RESULTS: Findings showed an increase in threat expectancy for only C- in the
      Experimental group during the test phase following avoidance learning to similar
      levels as during threat conditioning. Compared to the Control group, threat
      expectancy for both B- and C- remained higher in Experimental group. SCR and
      startle EMG data did not corroborate these findings. LIMITATIONS: Further
      research is needed to test the commonly held clinical assumption that avoidance
      can increase threat value. CONCLUSIONS: Low-cost avoidance maintains low-threat
      value of safety cues.

PMID- 30219565
TI  - On stopping rules and the sex ratio at birth.
AB  - One popular stopping rule intended to increase the rate of male births is to keep
      having babies until the first male is born. We show that such a stopping rule
      does not change the sex ratio at birth when the probability p that a birth
      produces a male is constant across a population. We show, however, that when p
      varies across couples, as evidence suggests that it does in the human population,
      with mean around 0.515 and standard deviation 0.05, then such a stopping rule
      tends to favour female births and the correct rule should be to stop procreating
      until the first female is born. But we also show that it does not seem that such
      stopping rules, even if favouring male births, can account for the dramatic
      increase in the rate of male births registered in some countries. Most of these
      conclusions have appeared in some form or other in various studies, but they are
      scattered across the literature and are very often presented using some heavy
      mathematical techniques. In this paper, we try to bring together these ideas and
      make them more accessible by analysing these stopping rules using the simplest
      mathematical tools possible.

PMID- 30219566
TI  - Profiles and predictors of risk for developmental delay: Insights gained from a
      community-based universal screening program.

PMID- 30219567
TI  - Characterization of cord blood interleukin 10 on aflatoxinB1-exposed patients
      with gestational diabetes.
AB  - BACKGROUND: Interleukin 10 (IL10) refers to a pleiotropic cytokine exerted
      immunoregulation. Aflatoxin B1 (AFB1) is a strong carcinogen, marked by causing
      immunosuppression. We determined the possible association between cord blood IL10
      and AFB1-exposed patients with gestational diabetes (GD). METHODS: Cord blood
      samples from non-GD adults (n = 3) and GD patients (n = 3) were harvested for
      determining representative serological parameters by use of biochemical assays
      and enzyme linked immunosorbent assay (ELISA) tests. RESULTS: As results, GD
      patients showed no statistical comparable clinical data (hepatic function, lipids
      metabolism, immune cell count) to those in controls or references. Interestingly,
      cord blood contents of AFB1 in GD patients were significantly increased when
      compared to those in non-GD controls, characterized with visibly increased cord
      blood IL10. CONCLUSIONS: Preliminary clinical data reveal that IL10 may function
      as a biomarker for immunoregulation in AFB1-exposed GD patients.

PMID- 30219568
TI  - The invasion speed of cell migration models with realistic cell cycle time
      distributions.
AB  - Cell proliferation is typically incorporated into stochastic mathematical models
      of cell migration by assuming that cell divisions occur after an exponentially
      distributed waiting time. Experimental observations, however, show that this
      assumption is often far from the real cell cycle time distribution (CCTD). Recent
      studies have suggested an alternative approach to modelling cell proliferation
      based on a multi-stage representation of the CCTD. In this paper we investigate
      the connection between the CCTD and the speed of the collective invasion. We
      first state a result for a general CCTD, which allows the computation of the
      invasion speed using the Laplace transform of the CCTD. We use this to deduce the
      range of speeds for the general case. We then focus on the more realistic case of
      multi-stage models, using both a stochastic agent-based model and a set of
      reaction-diffusion equations for the cells' average density. By studying the
      corresponding travelling wave solutions, we obtain an analytical expression for
      the speed of invasion for a general N-stage model with identical transition
      rates, in which case the resulting cell cycle times are Erlang distributed. We
      show that, for a general N-stage model, the Erlang distribution and the
      exponential distribution lead to the minimum and maximum invasion speed,
      respectively. This result allows us to determine the range of possible invasion
      speeds in terms of the average proliferation time for any multi-stage model.

PMID- 30219569
TI  - Effect of endocrine disruptors on the ratio of X and Y chromosome-bearing live
      spermatozoa.
AB  - Although equal numbers of X and Y spermatozoa are produced during
      spermatogenesis, the sex chromosome ratio in ejaculated spermatozoa can be
      altered by exposure to endocrine-disrupting chemicals (EDCs), which can be
      reflected by altered sex ratios at birth. Here, we hypothesized EDCs affect sperm
      functions and viability of X and Y chromosome-bearing human spermatozoa. After
      exposure to genistein (Gen), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD), dibromochloropropane (DBCP), and diazinon (Diaz), we evaluated
      motility, viability, capacitation, and differential viability of X and Y
      spermatozoa. All EDCs tested altered sperm viability, motility, and capacitation.
      Interestingly, the Y/X ratio of live spermatozoa was significantly lower in sperm
      treated with TCDD, DBCP, and Diaz than control spermatozoa. Our results suggest
      that some of EDCs have larger effects on the viability of Y spermatozoa than X
      spermatozoa, implicating that a reduction in Y sperm viability may result in a
      female-biased sex ratio of offspring at birth.

PMID- 30219570
TI  - Affordable Care Act's Medicaid Expansion and Use of Regionalized Surgery at High
      Volume Hospitals.
AB  - BACKGROUND: The Affordable Care Act (ACA)'s Medicaid expansion has increased
      access to surgical care overall. Whether it was associated with reduced
      disparities in use of regionalized surgery at high-volume hospitals (HVH) remains
      unknown. Quasi-experimental evaluations of this expansion were performed to
      examine the use of regionalized surgery at HVH among racial/ethnic minorities and
      low-income populations. STUDY DESIGN: Data from State Inpatient Databases (2012
      to 2014), the American Hospital Association Annual Survey Database, and the Area
      Resource File from Health Resources and Services Administration, were used to
      examine 166,558 nonelderly (ages 18 to 64) adults at 468 hospitals, who underwent
      1 of 4 regionalized surgical procedures in 3 expansion (KY, MD, NJ) and 2
      nonexpansion states (NC, FL). Thresholds of HVH were defined using the top
      quintile of visits per year. Interrupted time series were performed to measure
      the impact of expansion on use rates of regionalized surgery at HVH overall, by
      race/ethnicity, and by income. RESULTS: Overall, ACA's expansion was not
      associated with accelerated use rates of regionalized surgical procedures at HVH
      (odds ratio [OR] 1.016, p = 0.297). Disparities in use of regionalized surgical
      procedures at HVH among ethnic/racial minorities and low-income populations were
      unchanged; minority vs white (OR 1.034 p = 0.100); low-income vs high-income (OR
      1.034, p = 0.122). CONCLUSIONS: Early findings from ACA's Medicaid expansion
      revealed no impact on the use rates of regionalized surgery at HVH overall or on
      disparities among vulnerable populations. Although these results need ongoing
      evaluation, they highlight potential limitations in ACA's expansion in reducing
      disparities in use of regionalized surgical care.

PMID- 30219571
TI  - Processing number and length in the parietal cortex: Sharing resources, not a
      common code.
AB  - A current intense discussion in numerical cognition concerns the relationship
      between the processing of numerosity and other non-numerical quantities. In
      particular, it is a matter of debate whether number and other quantities (e.g.,
      size, length) are represented separately in the brain or whether they share a
      common generalized magnitude representation. We acquired high-resolution
      functional MRI data while adult subjects engaged in a magnitude comparison task
      involving either numerosity (i.e., which of the two sets has more elements?) or
      line length (i.e., which of the two lines is longer?). We compared the activation
      evoked by the two different types of quantity and observed a common recruitment
      of a vast portion of occipital and parietal cortices. Using MVPA, we demonstrated
      that some of the commonly activated regions represented the discrete and
      continuous quantities via a similar distance-dependent magnitude code. However,
      we found no effect of distance across the two quantity representations, failing
      to support the existence of a common, dimension invariant, generalized quantity
      code. Taken together, these findings indicate that although the processing of
      number and length is supported by partially overlapping neural resources,
      representations within these regions do not appear to be based on a common neural
      code.

PMID- 30219572
TI  - [Prevention of genetic diseases : the return of the family practitioner ?]
AB  - BACKGROUND: Information to kin is one of the major ethical problems of the new
      genetics. In France, the revised bioethics law in 2011 created the possibility
      for patients to authorize professionals, under certain conditions, to directly
      contact their relatives at risk. Beyond this, other actors, such as GPs, could
      however play a role in this process. METHODS: Our article is based on an
      ethnographic-type sociological study by observations and semi-structured
      interviews with patients (n=59) and genetic professionals (n=16) that took place
      from 2014 to 2016 in three genetic hospital wards in France and Canada. It
      focuses particularly on genetic predispositions to breast and ovarian cancers as
      well as genetic hemochromatosis. RESULTS: Because of its position as a primary
      care specialist, the general practitioner can play a decisive role in the process
      of informing relatives about genetic disorders. Upstream of the genetic test, the
      generalist, thanks to his knowledge of the family context of his patients, can
      play a referral role towards a specialized consultation. Downstream, it can also
      ensure a more effective follow-up of the information procedures undertaken by its
      patients thanks to the medical follow-up that it carries out. CONCLUSION: The
      data collected during our study highlight the unprecedented place that could be
      that of the general practitioner in the field of prevention in genetics. At the
      articulation between primary care and highly specialized care, it is the figure
      of the "family" doctor who seems to be called here to be renewed by genetics.

PMID- 30219573
TI  - Transformation of functional groups and environmentally persistent free radicals
      in hydrothermal carbonisation of lignin.
AB  - In this study, lignin was selected as the main component of waste biomass to
      synthesise carbonaceous adsorbents with environmentally persistent free radicals
      (EPFRs) through hydrothermal carbonisation (HTC) under different conditions. The
      HTC method with Fe(III) doping was superior for promoting dehydration and
      decarboxylation of lignin hydrochar than that with HTC Cu(II) doping. The
      deconstruction of oxygen-containing groups of lignin was reduced while
      esterification was enhanced by Fe(III). The Fe(III) addition was conducive to the
      formation of EPFRs as carbon-centred radicals with an adjacent oxygen atom and
      oxygen-centred radicals. A comparison of lignin with cellulose and d-xylose
      suggests that the formed EPFRs on lignin hydrochar were derived from their
      phenolic hydroxyl groups. A high removal efficiency of bisphenol A by lignin
      hydrochar was observed owing to oxygen-centred radicals, which activated H2O2 to
      produce OH. These results will facilitate the design and application of novel
      hydrochar materials with EPFRs.

PMID- 30219574
TI  - Potential enhancement of direct interspecies electron transfer for anaerobic
      degradation of coal gasification wastewater using up-flow anaerobic sludge
      blanket (UASB) with nitrogen doped sewage sludge carbon assisted.
AB  - Waste sewage sludge was converted into the novel conductive material of nitrogen
      doped sewage sludge carbon (N-SC) to enhance anaerobic degradation of coal
      gasification wastewater (CGW). The results indicated that N-SC played a
      significant role in enhanced efficiencies, with chemical oxygen demand (COD)
      removal efficiency increased by 25.4%, methane production rate improved by 68.1%
      and total volatile fatty acids (VFA) decreased by 37.5% than that of controlled
      reactor. The conductivity, activity of electron transport, and extracellular
      polymeric substances (EPS) of anaerobic sludge were remarkably enhanced with N
      SC, which promoted sludge granulation and supplied better conductive environment
      for microorganisms. The microbial community analysis revealed that potential
      enhancement of direct interspecies electron transfer (DIET) was achieved by
      electrical connection between enriched Geobacter, Pseudomonas and Methanosaeta
      with N-SC assisted, which enhanced the anaerobic degradation of CGW. Moreover,
      anaerobic degradation with N-SC had higher capacity to resist acidic shocks,
      facilitating the process stability.

PMID- 30219575
TI  - Simultaneous organosolv pretreatment and detoxification of municipal solid waste
      for efficient biobutanol production.
AB  - Municipal solid waste (MSW) was used as a source for biobutanol production via
      acetone, butanol, and ethanol (ABE) fermentation. Organosolv pretreatment was
      used for simultaneous extraction of inhibitors, particularly tannins, and
      pretreatment of lignocellulosic fraction prior to hydrolysis. The hydrolysates of
      the pretreated MSW contained appreciable amounts of sugars and soluble starch
      together with a tolerable amount of inhibitors for Clostridium acetobutylicum.
      The hydrolysate obtained from MSW pretreated with 85% ethanol at 120  degrees C
      for 30 min fermented to the highest ABE concentration of 13.06 g/L with the yield
      of 0.33 g/g carbon source. Through this process, 102.4 mg butanol, 40.16 mg
      acetone, and 13.14 mg ethanol were produced from each g of organic fraction of
      MSW (OFMSW). The pretreatment at mild conditions with higher ethanol
      concentration accompanied with the lowest glucose yield (0.145 g/g) and the
      highest starch recovery resulted in the uppermost ABE yield of 0.16 g/g OFMSW.

PMID- 30219576
TI  - Semi-continuous anaerobic co-digestion of chicken litter with agricultural and
      food wastes: A case study on the effect of carbon/nitrogen ratio, substrates
      mixing ratio and organic loading.
AB  - In this study, four agro-industrial substrates, chicken litter (CL), food waste
      (FW), wheat straw (WS) and hay grass (HG) were assessed as feedstock for
      anaerobic digestion (AD) under semi-continuous conditions at organic loading
      rates (OLRs) of 2.0-3.0 g TS/L.d and hydraulic retention time (HRT) of 20 days.
      Six different substrate mixtures were prepared such that the C/N ratio of each
      was 20 or more. Using principal component analysis 68.1% of data variability was
      explained. Biogas production from CL, as a single substrate, was 181.3 +/- 9.8mLN
      biogas/g VSadded at OLR of 2.0gTS/L.d. The optimum substrates mixture was
      CL:FW:WS 60:20:20, where 73.0%, 167.2% and 116.9% increase in total biogas
      production at OLR of 2.0, 2.5, 3.0gTS/L.d, respectively, compared to that from
      CL, was obtained. Digestate sequential fractionation revealed carbohydrate
      degradation is an important factor that can explain the variation in performance
      and production of biogas for feedstocks of balanced C/N ratio.

PMID- 30219577
TI  - Corrigendum to "Cow manure-loaded biochar changes Cd fractionation and
      phytotoxicity potential for wheat in a natural acidic contaminated soil"
      [Ecotoxicol. Environ. Saf. 162(2018) 348-353].

PMID- 30219578
TI  - Corrigendum to "Bioaccumulation of cadmium by Enterobacter sp. and enhancement of
      rice seedling growth under cadmium stress" [Ecotoxicol. Environ. Saf. 156 (2018)
      183-196].

PMID- 30219579
TI  - Dynamic agent of an injectable and self-healing drug-loaded hydrogel for
      embolization therapy.
AB  - Embolic agents are crucial for trans-catheter arterial embolization (TAE) in the
      treatment of various unresectable malignant tumors. Although solid particles,
      liquid oils, and some polymeric hydrogels have proved their capacities for
      embolic therapies, the low efficiency, time sensitivity, and cytotoxicity are
      still considered as challenges. In this study, we developed a three-component
      dynamic self-healing hydrogel to overcome these limitations. With the help of the
      Schiff-base bonding, both glycol-chitosan and carbazochrome, containing amine
      groups, react with dibenzaldehyde-terminated poly(ethylene-glycol) (DF-PEG),
      forming the dynamic self-healing hydrogels under a mild condition within 200 s.
      1H NMR and rheology test were used to characterize the Schiff-base formation and
      mechanical strength. Controlled-release of carbazochrome from different gelator
      concentrations of DF-PEG was also studied. Furthermore, in vivo evaluation of the
      embolization on rats showed the superior embolic effects of the injectable and
      self-healing hydrogel. Therefore, this new dynamic agent demonstrated the
      potential for application as a simple, inexpensive, and tunable embolic agent for
      cancer treatment and drug delivery system.

PMID- 30219581
TI  - Therapeutic potential of curcumin in diabetic complications.
AB  - Diabetes mellitus is an extremely prevalent endocrine disease and a major global
      public health concern. Diabetic complications, such as retinopathy, nephropathy,
      neuropathy and cardiovascular disease, are common and majorly impact a patient's
      quality of life. Curcumin, the major active component of turmeric, possesses
      extensive known pharmacological properties, including anti-inflammatory,
      antioxidant, and antitumor effects. Increasing evidence suggests that curcumin
      may offer protection against diabetic complications. The current review focuses
      on the possible molecular targets and pathways involved in diabetic complications
      and, in particular, the multi-target approach of curcumin in attenuating diabetic
      nephropathy, retinopathy, and neuropathy.

PMID- 30219582
TI  - Regulation of ER-mitochondria contacts by Parkin via Mfn2.
AB  - Parkin, an E3 ubiquitin ligase and a Parkinson's disease (PD) related gene,
      translocates to impaired mitochondria and drives their elimination via autophagy,
      a process known as mitophagy. Mitochondrial pro-fusion protein Mitofusins (Mfn1
      and Mfn2) were found to be a target for Parkin mediated ubiquitination. Mfns are
      transmembrane GTPase embedded in the outer membrane of mitochondria, which are
      required on adjacent mitochondria to mediate fusion. In mammals, Mfn2 also forms
      complexes that are capable of tethering mitochondria to endoplasmic reticulum
      (ER), a structural feature essential for mitochondrial energy metabolism, calcium
      (Ca2+) transfer between the organelles and Ca2+ dependent cell death. Despite its
      fundamental physiological role, the molecular mechanisms that control ER
      mitochondria cross talk are obscure. Ubiquitination has recently emerged as a
      powerful tool to modulate protein function, via regulation of protein subcellular
      localization and protein ability to interact with other proteins. Ubiquitination
      is also a reversible mechanism, which can be actively controlled by opposing
      ubiquitination-deubiquitination events. In this work we found that in Parkin
      deficient cells and parkin mutant human fibroblasts, the tether between ER and
      mitochondria is decreased. We identified the site of Parkin dependent
      ubiquitination and showed that the non-ubiquitinatable Mfn2 mutant fails to
      restore ER-mitochondria physical and functional interaction. Finally, we took
      advantage of an established in vivo model of PD to demonstrate that manipulation
      of ER-mitochondria tethering by expressing an ER-mitochondria synthetic linker is
      sufficient to rescue the locomotor deficit associated to an in vivo Drosophila
      model of PD.

PMID- 30219583
TI  - Chorion laeve accreta - Another manifestation of morbid adherence.
AB  - INTRODUCTION: Smooth muscle in the decidua of fetal membranes (membrane
      myofibers, MMF) is not mentioned in standard textbooks. METHODS: The current
      report presents collected observations on 52 patients with MMF at 2 institutions
      between 2004 and 2017 - including placentas, postpartum curettages, and
      hysterectomies. RESULTS: Clinical presentations include observation of adherent
      membranes during delivery, disrupted and incomplete membranes in placentas
      submitted for examination, postpartum bleeding associated with retained fetal
      membranes, association with membrane hematomas and membrane hemosiderin, morbidly
      adherent fetal membranes in hysterectomies; and association with grossly adherent
      pieces of tissue or nodules in fetal membranes. DISCUSSION: Although MMF can be
      an incidental microscopic observation in a routine placenta, the suggested
      diagnostic terminology when there are clinical and/or gross presentations is
      Chorion Laeve Accreta (ChLA). Further study is needed but MMF appears to be the
      fetal membrane counterpart of BPMF(basal plate myofibers), possibly due to damage
      of subjacent myometrium by trophoblastic proteases, so that shear stress during
      delivery causes myofibers to come out attached to the decidua of fetal membranes.
      Neither the prevalence of MMF, nor its reliability as a marker for placenta
      accreta is addressed in this collection. Association of MMF with BPMF, and
      recurrence of MMF, are documented; but the true frequency of these phenomena
      remains to be established.

PMID- 30219580
TI  - Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in
      class dissociative steroidal anti-inflammatory drug.
AB  - We report a first-in-patient study of vamorolone, a first-in-class dissociative
      steroidal anti-inflammatory drug, in Duchenne muscular dystrophy. This 2-week,
      open-label Phase IIa multiple ascending dose study (0.25, 0.75, 2.0, and 6.0
      mg/kg/day) enrolled 48 boys with Duchenne muscular dystrophy (4 to <7 years),
      with outcomes including clinical safety, pharmacokinetics and pharmacodynamic
      biomarkers. The study design included pharmacodynamic biomarkers in three
      contexts of use: 1. Secondary outcomes for pharmacodynamic safety (insulin
      resistance, adrenal suppression, bone turnover); 2. Exploratory outcomes for drug
      mechanism of action; 3. Exploratory outcomes for expanded pharmacodynamic safety.
      Vamorolone was safe and well-tolerated through the highest dose tested (6.0
      mg/kg/day) and pharmacokinetics of vamorolone were similar to prednisolone. Using
      pharmacodynamic biomarkers, the study demonstrated improved safety of vamorolone
      versus glucocorticoids as shown by reduction of insulin resistance, beneficial
      changes in bone turnover (loss of increased bone resorption and decreased bone
      formation only at the highest dose level), and a reduction in adrenal
      suppression. Exploratory biomarkers of pharmacodynamic efficacy showed an anti
      inflammatory mechanism of action and a beneficial effect on plasma membrane
      stability, as demonstrated by a dose-responsive decrease in serum creatine kinase
      activity. With an array of pre-selected biomarkers in multiple contexts of use,
      we demonstrate the development of the first dissociative steroid that preserves
      anti-inflammatory efficacy and decreases steroid-associated safety concerns.
      Ongoing extension studies offer the potential to bridge exploratory efficacy
      biomarkers to clinical outcomes.

PMID- 30219584
TI  - Hemihyperplasia: History of medicine assists medical genetics.
AB  - This paper examines the role of the history of medicine in case of congenital
      isolated hemihyperplasia. Isolated hemihyperplasia is a genetic disorder in which
      one side of the body grows more than the other, causing visible lateral asymmetry
      of the human body. The date of the occurrence of the genetic mutation that leads
      to hemihyperplasia is not known yet. The aim of the current research was to
      confirm or to disprove the fact that isolated hemihyperplasia was first described
      in the first half of the 19th century. Using the case of hemihyperplasia we aimed
      to demonstrate how historical analysis may assist medical genetics in cases when
      estimating a mutation date is necessary. Medical literature from 1573 onwards was
      searched for any mention of hemihypertrophy, hemihyperplasia, hemi-gigantism,
      partial gigantism, hemi-macrosomia and other possible descriptions for
      pathological lateral body overgrowth. Historical analysis suggests that the
      mutation in question occurred in the first half of the 19th century,
      approximately 200 years ago. This led to the appearance of hemihyperplasia and
      subsequent hemihyperplasia-including syndromes. An additional genetic research is
      needed for investigation of the development of the involved chromosomal region
      instability since this period. Such research may use the timeline orientation
      provided by the history of medicine.

PMID- 30219585
TI  - Changes to gait speed and the walk ratio with rhythmic auditory cuing.
AB  - BACKGROUND: Step length and cadence (i.e., step frequency or steps/minute)
      maintain an invariant proportion across a range of walking speeds, known as the
      walk ratio (WR = step length/cadence). While step length is a difficult parameter
      to manipulate, cadence is readily modifiable using rhythmic auditory cuing (RAC;
      e.g., synchronizing step timing to a metronome or music tempo). RESEARCH
      QUESTION: The purpose of this study was to determine the effects of RAC-guided
      cadences on enacted cadence, step length, WR, and gait speed during overground
      walking. METHODS: Sixteen healthy young adults repeatedly crossed a GAITRite
      electronic walkway while attempting to synchronize step timing to RAC-guided
      (metronome) tempos of 80 to 140 beats per minute. Mean absolute percent error
      (MAPE) was used to compare RAC tempos to enacted cadence. Repeated-measures
      analyses of variance were performed to test for the effects of RAC on cadence,
      step length, WR, and gait speed. Moreover, simple linear regressions were used to
      determine the precise stepwise relationship between RAC conditions and each
      variable. RESULTS: Participants successfully matched their cadence to RAC beats
      (MAPE < 1.1%). Cadence increased proportionally to RAC (linear regression slope =
      1.02), while step length also increased but at a slower rate (slope = 0.40).
      These dissimilar slopes resulted in a modified WR that systematically decreased
      with increasing cadence, although ultimately gait speed increased with increasing
      cadence (slope = 1.41). This relationship indicates that every 10 steps/minute
      incremental increase in cadence corresponded with a 14 cm/s increase in gait
      speed. SIGNIFICANCE: Gait speed appears to increase in a predictable manner when
      cadence is guided by RAC during overground walking irrespective of apparent
      changes to the WR.

PMID- 30219586
TI  - Benign epilepsy with centrotemporal spikes - Current concepts of diagnosis and
      treatment.
AB  - Benign epilepsy with centrotemporal spikes (BECTS) is the most common focal
      epilepsy of the childhood and also one of the best known. It has a proclivity to
      start at a particular age and remit spontaneously before adolescence. Majority of
      patients may avoid long-term treatment, because of the mild course and very good
      outcome. Only few patients may present cognitive deficits if the proper treatment
      is not implied. BECTS is a part of heterogeneous group of syndromes that consists
      of Landau-Kleffner Syndrome (LKS), Continuous Spike-and-Wave during Sleep (CSWS)
      and Atypical benign partial epilepsy (ABPE). These syndromes may be also a result
      of various trajectories that BECTS may evolve to. Disease is suggested to have
      genetic origins, as some patients have relatives with different types of
      epilepsy. The discovery of the pathogenic mechanism of the disease and
      implementation of targeted therapy belong to the main challenges in the treatment
      of these patients.

PMID- 30219587
TI  - Central liponeurocytoma as a clinical entity.
AB  - INTRODUCTION: Liponeurocytomas are mostly localized in cerebellar hemispheres and
      the second most common location is the vermis. It is rarely observed within the
      intracranial ventricles. Here, we present a case of liponeurocytoma located in
      the right lateral ventricle and the systematic review of the literature. STATE OF
      THE ART: We searched PubMed with keyword 'central liponeurocytoma' and the
      references of the related articles. There were no language or year restrictions.
      We included articles focusing on liponeurocytomas located in the central nervous
      system leaving a total of 17 articles and 21 reported cases. CLINICAL
      IMPLICATIONS: A 62-year-old female presented with confusion and mental
      disorientation without any other neurological deficit. Her magnetic resonance
      imaging (MRI) revealed a lateral ventricle located mass lesion which was
      hypointense on T1-weighted images (WI) and heterogeneously hyperintense on T2-WI
      with cystic component. Via craniotomy, yellow-beige colored, soft and moderately
      vascularized mass lesion was gross totally resected. Despite postoperative MRI
      revealed total resection, patient had left-sided hemiparesis. The patient
      recovered well in her postoperative period and there was no recurrence on her 6th
      month follow-up MRI. FUTURE DIRECTIONS: Intraventricular liponeurocytoma has a
      favorable clinical course, and radiological features may be useful in the
      diagnosis of this rare tumor before surgery. Supratentorial intraventricular
      location should be kept in mind in the differential diagnosis of the lateral
      ventricular tumors.

PMID- 30219588
TI  - Docking and pharmacodynamic studies on hGAT1 inhibition activity in the presence
      of selected neuronal and astrocytic inhibitors. Part I.
AB  - Inhibition of 4-aminobutanoic acid (GABA) uptake is a strategy for enhancing GABA
      transmission. The utility of this approach is demonstrated by the successful
      development of such agents for the treatment of epilepsy and pain. Existing
      reports on acute brain slice preparations indicate the intersecting of
      complementary channels and receptors sets between astrocytes and neurons cells.
      Thorough analysis of astroglial cells by means of molecular and functional
      studies demonstrated their active modulatory role in intercellular communication.
      The chemical interactions between sixteen GABA analogues and isoform of hGAT1 is
      outlined in the light of molecular docking results. In the in vivo part
      antinociceptive properties of racemic nipecotic acid, its R and S enantiomers and
      isonipecotic acid, each administered intraperitoneally at 3 fixed doses (10, 30
      and 100 mg/kg), were assessed in a thermally-induced acute pain model i.e. the
      mouse hot plate test. Docking analyses provided complex binding energies,
      specific h-bond components, and h-bond properties, such as energies, distances
      and angles. In vivo tests revealed statistically significant antinociceptive
      properties of isonipecotic acid (10 and 30 mg/kg), R-nipecotic acid (30 and 100
      mg/kg) and S-nipecotic acid (100 mg/kg) in mice. The docking data endorse the
      hypothesis of correlation between the strength of their chemical interactions
      with hGAT1 and analgesic action of studied compounds.

PMID- 30219590
TI  - Combined toxicity of organophosphate flame retardants and cadmium to Corbicula
      fluminea in aquatic sediments.
AB  - Organophosphate flame retardants (OPFRs), as alternatives to polybrominated
      biphenyl ethers (PBDEs), are frequently detected in various environmental
      matrices. Owing to urbanization and industrial pollution, co-contamination of
      OPFRs and heavy metals is ubiquitous in the environment. The toxicity of OPFRs in
      aqueous phase is a significant concern, but uncertainty still exists regarding
      the co-toxicity to benthic organisms of OPFRs and metals in sediments. Hence, we
      explored the physiological response of Corbicula fluminea to OPFRs and Cd in
      sediments. The results indicated that the antioxidant system in the clams was
      stimulated in the presence of OPFRs and Cd, and the oxidative stress increased
      with increasing concentrations of OPFRs. In contrast, the cytochrome P450
      (CYP450) content and acetylcholinesterase (AChE) activity were reduced by
      exposure to both OPFRs and Cd. The cytochrome P450 4 family (CYP4) mRNA
      expression and OPFR toxicity were lower than those in previously reported
      experiments conducted in the water phase. Moreover, the expression levels of
      metallothionein (MT) and AChE mRNA decreased when OPFRs and Cd were present
      together. The highest integrated biomarker response (IBR) index (IBR = 15.41) was
      observed in the presence of 45 mg kg-1 Cd + 200 mg kg-1 OPFRs, rather than the 45
      mg kg-1 Cd + 400 mg kg-1 OPFRs treatment (IBR = 9.48). In addition, CYP450 and
      AChE in the digestive glands of C. fluminea exhibited significant correlations
      with the concentration of the OPFR/Cd mixture (p < 0.01) and could be effective
      biomarkers for OPFR and Cd co-contamination. The results potentially contribute
      to more realistic predictions and evaluations of the environmental risks posed by
      OPFRs in aquatic sediments contaminated with heavy metals, particularly with
      respect to the risk to benthic organisms.

PMID- 30219589
TI  - Photodegradation of fluorotelomer carboxylic 5:3 acid and perfluorooctanoic acid
      using zinc oxide.
AB  - Occurrence of per- and poly-fluoroalkyl substances (PFASs) in the environment and
      biota has raised a great concern to public health because these compounds are
      persistent, bioaccumulative, and toxic. Biodegradation of polyfluoroalkyl
      substances, particularly long-chain fluorotelomer-based products, can lead to
      production of various short-chain PFASs, with 5:3 fluorotelomer carboxylic acid
      (referred as 5:3 FTCA hereafter) as a dominant polyfluoroalkyl metabolite.
      Perfluoroalkyl acids, particularly perfluorooctanoic acid (PFOA), are toxic and
      current removal methods are not cost-effective. This study reports the
      photodegradation of 5:3 FTCA and PFOA using ZnO as a photocatalyst under neutral
      pH and room temperature conditions. Under long UV wavelength (365 nm), both
      tetrapod and commercial ZnO can photodegrade 5:3 FTCA. Five removal products
      perfluorohexanoic acid, perfluoropentanoic acid, perfluorobutyric acid, 5:2
      fluorotelomer carboxylic acid (5:2 FTCA), and inorganic fluoride-were identified,
      with PFBA and F- as dominant end products. SEM and XPS high-resolution scans on
      the surface of the utilized ZnO showed less units of CF2 than that in 5:3 FTCA,
      supporting occurrence of photodegradation of 5:3 FTCA by ZnO. Defluorination of
      PFOA was not observed with ZnO only, but at pH 5 and in the co-presence of Fe
      citrate. PFOA defluorination increased from 0.93% after 3 days of UV light
      exposure to 3.9% after additional 135 h under direct sunlight exposure. To the
      authors' best knowledge, this is the first report studying ZnO-catalyzed
      photodegradation of 5:3 FTCA, and examining the Fe co-addition for PFOA
      defluorination.

PMID- 30219592
TI  - Kidney Tattoos.

PMID- 30219591
TI  - Antipsychotic and benzodiazepine use and brain morphology in schizophrenia and
      affective psychoses - Systematic reviews and birth cohort study.
AB  - The aim of this paper was to investigate differences in brain structure volumes
      between schizophrenia and affective psychoses, and whether cumulative lifetime
      antipsychotic or benzodiazepine doses relate to brain morphology in these groups.
      We conducted two systematic reviews on the topic and investigated 44
      schizophrenia cases and 19 with affective psychoses from the Northern Finland
      Birth Cohort 1966. The association between lifetime antipsychotic and
      benzodiazepine dose and brain MRI scans at the age of 43 was investigated using
      linear regression. Intracranial volume, sex, illness severity, and
      antipsychotic/benzodiazepine doses were used as covariates. There were no
      differences between the groups in brain structure volumes. In schizophrenia,
      after adjusting for benzodiazepine dose and symptoms, a negative association
      between lifetime antipsychotic dose and the nucleus accumbens volume remained. In
      affective psychoses, higher lifetime benzodiazepine dose associated with larger
      volumes of total gray matter and hippocampal volume after controlling for
      antipsychotic use and symptoms. It seems that in addition to antipsychotics, the
      severity of symptoms and benzodiazepine dose are also associated with brain
      structure volumes. These results suggest, that benzodiazepine effects should also
      be investigated also independently and not only as a confounder.

PMID- 30219593
TI  - Complete white out of a single transplanted lung in the immediate postoperative
      period.
AB  - Vascular complications are rare but serious events following lung
      transplantation. Of the potential adverse events post lung transplant, pulmonary
      vein thrombosis is rare but often fatal. Our case describes a 54 year-old male
      who underwent single left lung transplantation and suddenly became
      hemodynamically unstable shortly after the procedure. The diagnosis of acute
      pulmonary vein thrombosis was made with the use of trans-esophageal
      echocardiography identifying complete occlusion of the left upper pulmonary vein
      which led to successful surgical thrombectomy and revision of the anastomosis.

PMID- 30219594
TI  - FTIR characterization of the setting reaction of biodentineTM.
AB  - OBJECTIVE: To provide insight of the setting reactions of BiodentineTM, a
      hydraulic calcium silicate cement, based upon observations using Fourier
      Transform Infra-Red (FTIR) spectroscopy. METHODS: FTIR spectra of components
      before and during the setting reaction were taken using the attenuated total
      reflectance (ATR) technique. Measurements over wavelengths 600-4000cm-1 were
      taken at regular intervals for two days. RESULTS: FTIR spectrum of BiodentineTM
      powder revealed a number of peaks from 650 to 1100cm-1 and a plateau from 1400 to
      1500cm-1, indicative of SiO and CO3-bonding, while the mixing fluid exhibited
      water peaks. Results following mixing displayed three distinct regimes; (i)
      incubation phase, during the first 35min, when minimal change occurred, (ii)
      rapid transitory stage, between 35 and 90min, when major changes occurred, and
      (iii) slow sustained reaction stage for remaining 45h. Incubation appears to be
      associated with the presence of CO3-peaks. The transition region indicates
      formation of CaOH and Jennite OH-peaks, anticipated intermediate reaction phases.
      At 90min, the end of second stage, CaOH and Jennite are replaced by a dominant
      Portlandite (Ca(OH)2)-peak and minor presence of Tobermorite, another anticipated
      intermediate phase, and water reduction. During the following 45h Portlandite and
      Tobermorite decline while the water peak increases. SIGNIFICANCE: FTIR can be
      used to follow the chemical reactions in dental cements and provides insight into
      the relatively slow setting reactions of hydraulic calcium silicate cements.

PMID- 30219595
TI  - From 1H NMR-based non-targeted to LC-MS-based targeted metabolomics strategy for
      in-depth chemome comparisons among four Cistanche species.
AB  - The great orthogonality between 1H NMR spectroscopy and LC-MS implies that their
      deployments in series could offer an opportunity to gain the qualified molecular
      markers via comparative metabolomics, and an attempt was made here to propose an
      integrated strategy namely "from 1H NMR-based non-targeted to LC-MS-based
      targeted metabolomics". In-depth chemome comparisons of Cistanche plants, such as
      C. deserticola, C. salsa, C. tubulosa, and C. sinensis, that possess dramatic
      economic and ecological benefits for the arid regions in the northwest China
      attributing to their dramatic medicinal and edible values, were employed to
      verify the applicability. 1H NMR-based non-targeted matabolomics acted as the
      survey experiment to find those signals offering decisive contributions towards
      the species discrimination, and the signals were translated to a set of putative
      identities, eighteen ones in total, through matching with authentic compounds and
      referring to some accessible databases. Afterwards, an advanced LC-MS platform
      assembling reversed phase liquid chromatography, hydrophilic interaction liquid
      chromatography, and tailored multiple reaction monitoring, was introduced to
      simultaneously quantify those eighteen potential markers in a single analytical
      run, because those candidates exhibited great polarity span as well as wide
      content range. Significant species differences occurred amongst their chemome
      patterns. Echinacoside, acteoside, betaine, mannitol, 6-deoxycatalpol, sucrose,
      and 8-epi-loganic acid were disclosed as the markers enabling the discrimination
      of those four species. The findings offered an alternative tool to differentiate
      Cistanche plants. More importantly, the strategy namely "from 1H NMR-based non
      targeted to LC-MS-based targeted metabolomics" facilitates the pursuit of
      molecular markers among analogue plants, and thereby provides a promising choice
      for in-depth chemome comparison.

PMID- 30219596
TI  - A whole blood sample-to-answer polymer lab-on-a-chip with superhydrophilic
      surface toward point-of-care technology.
AB  - An innovative sample-to-answer (S-to-A) polymer lab-on-a-chip (LOC) with a blood
      plasma separator based on asymmetric capillary force has been proposed,
      developed, and completely characterized for point-of-care technology (POCT)
      applications. A spray layer-by-layer (LbL) nanoassembly coating has been applied
      for the superhydrophilic surface onto the cyclic olefin copolymer (COC). Then,
      the developed superwetting surfaces were designed and optimized for three device
      applications such as lateral transportation of whole blood in the device by
      capillary pumping, on-chip whole blood/plasma separation with an asymmetric
      capillary force, and detection using a capillary-driven lateral flow colorimetric
      assay. Integrating three primary components of the devices, the S-to-A polymer
      LOC platform has been effectively confirmed for the lateral flow colorimetric
      assay of bovine serum albumin (BSA) from unprocessed human whole blood without an
      external power resource.

PMID- 30219597
TI  - An LC-MS/MS analysis for seven sex hormones in serum.
AB  - BACKGROUND: Comprehensive serum sex hormone profiling is essential for monitoring
      the occurrence and development of many related diseases. However, the current
      methods for multi-class sex hormone detection were always lack of Standard
      Reference Material (SRM) certification and suffered from large sample
      consumption. For improvement, we developed a new liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method focused on SRM certification and minimization
      of serum consumption for simultaneous quantification of seven mainstream serum
      sex hormones including estrogens (estrone E1, estradiol E2 and estriol E3),
      androgens (testosterone T, androstenedione AD, dehydroepiandrosterone DHEA) and
      progestogens (progesterone P). METHODS: To achieve one-batch analysis, a
      straightforward strategy was designed and carefully optimized. Schematically,
      serum was firstly spiked with isotope-labeled internal standards. Then, liquid
      liquid extraction was performed with methyl tert-butyl ether. After drying under
      nitrogen, dansyl chloride was introduced for derivatization. Finally, the mixture
      was submitted to LC-MS/MS for quantification. RESULTS: The limit of
      quantification was 0.005 ng/mL for E1, E2 and E3, 0.01 ng/mL for T, P and AD,
      0.25 ng/mL for DHEA. Inter- and intra-assay CVs were less than 11.8%. The
      selectivity was proved satisfactory by interference spiking tests. With
      systematical SRM validation, the mean bias of -5.4 to 4.7% was observed, which
      indicated excellent method reliability. We found significant positive bias in
      chemiluminescence immunoassay (CLIA) detection comparing with current method,
      which promoted us to reconsider our previous results on sex hormone regulation in
      male patients with coronary atherosclerotic disease. After redetecting the
      related samples, modified and improved conclusions were proposed. CONCLUSIONS: A
      LC-MS/MS method for multi-class serum sex hormone profiling was developed with
      SRM certification and minimized serum consumption. Taking advantages of such
      reliable method, the previous CLIA-based research findings on sex hormone
      regulation in male patients with coronary atherosclerosis were modified and
      improved after redetecting the same sample-pool.

PMID- 30219598
TI  - Diffusion ordered NMR spectroscopy measurements as screening method of potential
      reactions of API and excipients in drug formulations.
AB  - In the development of new pharmaceutical formulations it is important to consider
      the possible interactions between the active pharmaceutical ingredient (API) and
      excipients which is a well-known problem. The objective of the work presented
      here was to investigate such reactions by means of diffusion ordered NMR
      spectroscopy (DOSY). The known reaction of 5-aminosalicylic acid (5-ASA) and the
      excipient citric acid was studied. Three reaction products have been verified by
      DOSY, 1H NMR and HPLC measurements. Despite a poor separation in the DOSY
      diagram, the reaction products could be assign due to the processing of
      thoughtful selected parts of the signals. The reaction of 5-ASA with formic acid
      and benzocaine with dibutyl phthalate was also studied by means of DOSY
      experiments.

PMID- 30219599
TI  - Development of formaldehyde dehydrogenase-coupled assay and antibody-based assays
      for ALKBH5 activity evaluation.
AB  - N6-methyladenosine (m6A) is the most prevalent internal modification of
      eukaryotic messenger RNA (mRNA). Until now, two RNA demethylases have been
      identified, including FTO (fat mass and obesity-associated protein) and ALKBH5
      (alpha-ketoglutarate-dependent dioxygenase alkB homologue 5). As a mammalian m6A
      demethylase, ALKBH5 significantly affects mRNA export and RNA metabolism as well
      as the assembly of mRNA processing factors in nuclear speckles, and ALKBH5 may
      play a significant role in these biological processes. Nevertheless, no modulator
      of ALKBH5 has been reported. The reason for that may be the lack of in vitro
      assays for ALKBH5 inhibitor screening. Herein, we describe the development of two
      homogeneous assays for ALKBH5 using N6-methyladenosine as substrate with
      different principles. Using ALKBH5 recombinant, we developed a formaldehyde
      dehydrogenase coupled fluorescence based assay and an antibody based assay for
      the activity evaluation of ALKBH5. These robust coupled assays are suitable for
      screening ALKBH5 inhibitors in 384-well format (Z' factors of 0.74), facilitating
      the discovery of modulators in the quest for the regulation of biological
      processes.

PMID- 30219600
TI  - Removal of inert COD and trace metals from stabilized landfill leachate by
      granular activated carbon (GAC) adsorption.
AB  - Landfills in Germany are currently approaching stabilization phase; as a result
      removal of inert organics and potentially toxic elements in the leachate is
      becoming a primary concern. Dissolved air floatation (DAF) at the secondary stage
      reduces only 27% of the residual chemical oxygen demand (COD) in the investigated
      treatment systems; downstream granular activated carbon (GAC) units are required
      to further reduce COD concentration by 40-56% to meet indirect discharge or
      direct discharge limits respectively. Therefore, in this study performance in
      terms of COD and trace metals adsorption of different types of granular activated
      carbon were compared over different contact times and dosages. GAC 1 with
      Brunauer-Emmett-Teller (BET) surface area of 719.5 +/- 2.1 m2/g and average pore
      diameter (D) of 4.81 nm was identified to be inappropriate for treatment of
      leachate from this landfill. GAC 2 (with BET of 1513.7 +/- 6.4 m2/g and D of 3.50
      nm) was feasible for COD reduction from DAF-pretreated leachate, while GAC 3
      (with BET of 644.5 +/- 2.6 m2/g and D of 5.65 nm) can be coupled either with
      biological step alone, or as a tertiary step after the DAF unit. Moreover, as COD
      is the primary remaining contaminant of interest after secondary and tertiary
      treatment, spectrometer probes provide a close estimation of COD concentration
      for use in online monitoring. Beside COD removal, GAC 3 also confirmed the
      effectiveness of trace metals adsorption even at trace level, as it removed 66,
      64, 48, 47, 43, and 25% of copper, cobalt, chromium, manganese, nickel, and zinc,
      respectively.

PMID- 30219601
TI  - New Roles for an Ancient Factor.
AB  - In 1996, Hyejin Kang and Erin Schuman, in search of new functions for the
      secreted growth factor brain-derived neurotrophic factor (BDNF), identified the
      protein synthesis requirement of BDNF in regulating synaptic plasticity. This
      landmark paper identified one of the first tractable pathways in the quest to
      dissect the complex process of synaptic remodeling and revealed the critical role
      for this neurotrophin in regulating long-term memory.

PMID- 30219602
TI  - Effect of hyperlipidaemia to accelerate intervertebral disc degeneration in the
      injured rat caudal disc model.
AB  - BACKGROUND: Dyslipidaemia is a well-known risk factor for the development of
      atherosclerosis, however, little is known about the effect of dyslipidaemia on
      intervertebral disc degeneration (IVDD). Thus, the purpose of this study is to
      investigate the relationship between dyslipidaemia and IVDD, and to identify the
      possible mechanism by which dyslipidaemia aggravates the degeneration of
      intervertebral discs. METHODS: Hyperlipidaemia rats were induced, thirty male
      Wistar rats were randomly divided into two groups: normal chow diet control group
      (CON) and high-fat diet group (HFD) for 8 weeks. And then, a rat disc
      degeneration model was established, rats were divided into three experimental
      groups: the normal chow diet + sham surgery group (CON-Sham); the normal chow
      diet + needle puncture group (CON-NP); and the high-fat diet + needle puncture
      group (HFD-NP), all rats were continually fed with normal chow diet or HFD 8
      weeks. At the end of the experiment, the discs were harvested and
      histomorphological analysis, immunohistochemistry staining, real-time PCR and
      western blot were performed for all groups. RESULTS: The degenerative
      histological score of disc in the HFD-NP group was significantly higher than the
      CON-NP group. Immunohistochemical analysis revealed remarkable reductions in
      aggrecan and collagen type II expressions, and significant increases in IL-1beta,
      TNF-alpha, MMP-13, HIF-1alpha and P65 expression in the HFD-NP group. RT-PCR and
      western blot analysis showed that the mRNA levels and protein expressions of MMP
      13 and TIMP-1 were higher in the HFD-NP group. CONCLUSIONS: Hyperlipidaemia
      resulted in an exaggerated degenerative changes and altered expression and
      transcription of the degeneration-associated molecules in the rat disc tissue.
      These results raise the possibility that hyperlipidaemia may accelerate the
      progression of disc degeneration.

PMID- 30219603
TI  - A comparative clinical and functional assessment of cortical button versus suture
      anchor in distal biceps brachii tendon repair.
AB  - PURPOSE: The studies comparing the fixation methods being used for the ruptured
      distal biceps brachii tendon reinsertion show similar outcomes of cortical button
      and suture anchors usage, however, longer follow-up studies remain necessary. The
      goal of this study was to compare the clinical and functional three-year outcomes
      of the cortical button in contrast to the suture anchor fixation. METHODS: A
      retrospective cohort study comprised of 28 males on average 3 years after
      surgical reinsertion of the distal biceps brachii tendon with the use of a
      cortical button (Group I, n = 11) or a suture anchor (Group II, n = 17). The
      outcomes assessed were range of elbow joint and forearm motion (ROM), arm
      circumferences, visual analogue scale (VAS), Mayo Elbow Performance Index (MEPI),
      Quick Disability of the Arm, Shoulder, and Hand (Quick DASH) and forearm flexor
      and supinator muscle torques measured under isometric and isokinetic conditions.
      RESULTS: The comparison between the two studied groups revealed no statistically
      significant differences in ROM (p = 0.24-1.00), circumferences (p = 0.15-0.50),
      VAS (p = 0.71), MEPI (p = 0.23), Quick DASH (p = 0.61) or in the obtained muscle
      torque values (p = 0.07-1.00). However, differences in supination ROM between the
      surgical and non-surgical side were found in both groups (p = 0.01-0.02), and
      differences in pronation (p = 0.02) were found in Group II. The muscle torque
      values obtained in the surgical, dominant limb were lower than those in the
      nonsurgical, nondominant limb. CONCLUSION: The comprehensive comparison of three
      year outcomes of cortical button versus suture anchor fixations did not favour
      one fixation method over the other, and the results justify the clinical usage of
      both methods.

PMID- 30219604
TI  - Federated multi-site longitudinal study of at-risk mental state for psychosis in
      Japan.
AB  - There has been recent accumulation of evidence and clinical guidance regarding
      the at-risk mental state (ARMS) for psychosis. However, most studies have been
      observational cohort and intervention studies of Western populations. To assess
      the validity of the ARMS concept and the transition rate to psychosis in a non
      Western nation, we retrospectively combined and analyzed clinical data of
      individuals diagnosed with ARMS who were prospectively followed-up at three
      specialized clinical services for ARMS in Japan. In total, we included 309
      individuals with ARMS, of whom 43 developed overt psychosis. We estimated
      cumulative transition rates to psychosis with the Kaplan-Meier method, obtaining
      rates of 12% at 12, 16% at 24, 19% at 36, and 20% at 48 months. Only two
      individuals reported past cannabis use. Despite several differences among the
      three sites, transition rates did not differ among them. Furthermore, the
      transition rate of children aged between 14 and 17 years did not differ from that
      of individuals aged 18 years or older. Regression analysis revealed that meeting
      the brief limited intermittent psychotic symptoms (BLIPS) criterion was
      associated with an increased risk of transition to psychosis, whereas genetic
      risk factors were not. Although antipsychotic prescription was relatively
      frequent in this cohort, there was no evidence supporting frequent use of
      antipsychotics for this population. In conclusion, our findings support the
      assertion that the current concept of ARMS is applicable in Japan. Development of
      local clinical guidelines and training for clinicians is necessary to disseminate
      this concept to more clinical settings.

PMID- 30219605
TI  - Simulated car driving and its association with cognitive abilities in patients
      with schizophrenia.
AB  - OBJECTIVES: Patients with schizophrenia commonly suffer from impairments in
      various aspects of cognition. These deficits were shown to have detrimental
      effects on daily life functioning and might also impair car driving. This study
      is the first to examine driving behaviour of patients with schizophrenia using an
      advanced driving simulator, and to explore the role of cognitive abilities of
      people with schizophrenia for driving. METHODS: Non-acute patients with
      schizophrenia (n = 31) and healthy comparison participants (n = 31) performed a
      comprehensive neuropsychological assessment and driving simulator rides.
      Neuropsychological and driving performances were compared between groups.
      Moreover, associations were explored between cognitive functions and driving
      behaviour in the entire group. RESULTS: Patients with schizophrenia revealed
      impairments in multiple aspects of cognition. In the driving simulator, patients
      with schizophrenia showed no indication of deviant driving in terms of number of
      collisions or reacting to critical situations, and even showed better lane
      control compared to healthy individuals. However, patients with schizophrenia
      drove significantly slower than healthy individuals, and caused more hindrance to
      the car behind while merging on the motorway. Slower driving was associated with
      lower test scores on attention and processing speed. Hindering the car behind was
      associated with test performance on planning and inhibition. CONCLUSIONS: It is
      concluded that driving of patients with schizophrenia is characterized by a
      relatively slow speed, and can also be impaired in certain aspects, i.e.
      hindering a car behind while merging. Cognitive functions are crucial for
      driving, and should be target of treatment.

PMID- 30219606
TI  - Review of outcomes of 500 consecutive cases of non-melanoma skin cancer of the
      head and neck managed in an oral and maxillofacial surgical unit in a District
      General Hospital.
AB  - We provide a non-melanoma skin cancer (NMSC) service for skin cancers of the head
      and neck in the south-west of England. We hypothesised that certain anatomical
      sites such as the nose and eyelid would have a higher incidence of close or
      involved margins than others, and that the choice of repair might influence the
      excised margins. We therefore retrospectively analysed the data of 500
      consecutive NMSC that were operated on in the oral and maxillofacial surgery unit
      of Taunton and Somerset NHS Trust. The database reports were crosschecked against
      the Trust's own pathology reporting system to ensure that they were accurate.
      Data collected included clinical and personal details of patients, anatomical
      sites, type of reconstruction, histopathological diagnosis, excision margins, and
      complications. Of the 500 patients reviewed 362 (72%) were basal cell carcinomas
      (BCC) and 138 (28%) squamous cell carcinomas (SCC). The outcomes of 243 patients
      treated by primary closure, 134 treated by reconstruction with local flaps, and
      123 treated by skin grafts, were reviewed with particular attention paid to the
      anatomical site and excision margins. There was an overall incomplete excision
      rate of 10.8% (n=54) and 29 patients developed complications (5.8%). We confirmed
      that rates of close or incomplete margins are more likely in certain anatomical
      sites such as the nose, forehead, and ear. The rate of involved margins was
      unaffected by choice of surgical technique.

PMID- 30219607
TI  - Letter to editor re: Refeeding syndrome in adults receiving total parenteral
      nutrition: An audit of practice at a tertiary UK centre.

PMID- 30219608
TI  - Re: Letter to the Editor - Comment on: 'Sufficient levels of 25-hydroxyvitamin D
      and protein intake required to increase muscle mass in sarcopenic older adults -
      The PROVIDE study'.

PMID- 30219609
TI  - Relationship between dietary quality, determined by DASH score, and
      cardiometabolic health biomarkers: A cross-sectional analysis in adults.
AB  - BACKGROUND AND AIMS: The relationship between dietary patterns and
      cardiometabolic disease is of increasing interest. However, limited data
      regarding the association between dietary quality and biomarkers of
      cardiometabolic health exist. Therefore the aim of this work was to examine
      potential associations between dietary quality, assessed using the Dietary
      Approaches to Stop Hypertension (DASH) dietary quality score, adiposity and
      biomarkers of glucose homeostasis, lipoprotein metabolism and inflammation in a
      cross-sectional sample of 1493 men and women. METHODS: Anthropometric
      measurements included BMI, hip and waist circumference (WC). Serum acute-phase
      reactants, adipocytokines, pro-inflammatory cytokines and white blood cell (WBC)
      counts were determined. Lipoprotein particle size and subclass concentrations
      were measured using nuclear magnetic resonance (NMR) spectroscopy. Insulin
      resistance was calculated by homeostasis model assessment (HOMA-IR). RESULTS:
      Higher dietary quality was associated with lower BMI (P < 0.05), WC (P < 0.001),
      tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), WBC and
      plasminogen activator inhibitor-1 (PAI-1) concentrations (P < 0.01) and reduced
      insulin resistance (P < 0.05). In addition less small low density lipoprotein
      (LDL) and small high density lipoprotein (HDL) particles and less large very low
      density lipoprotein (VLDL) particles were observed among those with better
      dietary quality (P < 0.001). Individuals in the top DASH quartile had a 54% and
      48% lower likelihood of central obesity and metabolic syndrome (MetS),
      respectively, than those in the lowest DASH quartile (P < 0.05). CONCLUSIONS: Our
      data suggest that higher quality diet is associated with improved adiposity
      measures and a less insulin resistant, pro-inflammatory, pro-thrombotic and pro
      atherogenic cardiometabolic profile which may impact on central obesity and MetS
      risk. These findings, which may be of clinical and public health significance in
      terms of dietary approaches to promote cardiometabolic health, warrant further
      examination.

PMID- 30219610
TI  - Concentrations of endocrine disrupting chemicals in newborn blood spots and
      infant outcomes in the upstate KIDS study.
AB  - BACKGROUND: Novel methodologies to quantify infant exposures to endocrine
      disrupting chemicals (EDCs) for population-based studies are needed. OBJECTIVES:
      We used newborn dried blood spots to quantify three EDCs and their associations
      with infant outcomes in the Upstate KIDS Cohort. METHODS: We measured bisphenol A
      (BPA), perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in
      2071 singleton and 1040 twin infants born to mothers in New York State. We log
      transformed concentrations after rescaling by their standard deviations and
      modeled each in relation to gestational age, birthweight, length, head
      circumference and Ponderal Index (PI) using linear regression techniques. All
      models were adjusted for maternal age, body mass index, education, infertility
      treatment and parity. Generalized estimating equations with robust standard
      errors were used to assess the associations for twins. RESULTS: Chemicals were
      largely quantified above the limits of detection (>99% for PFOS and PFOA; 90% for
      BPA). Overall, we observed no significant associations between PFASs and birth
      size irrespective of plurality of birth. However, among twins, BPA was associated
      with decreases in gestational age (adjusted beta = -0.09 weeks; 95% Confidence
      Interval (CI): -0.16, -0.02) and birthweight (adjusted beta = -32.52 g; 95% CI: 
      60.99, -4.05), head circumference (adjusted beta = -0.18 cm; 95% CI: -0.38, 
      0.02) and increased PI in singletons (adjusted beta = 0.02 cm; 95% CI: 0.004,
      0.04). CONCLUSION: We observed negative associations between BPA and birth size
      in twins. Our findings demonstrate the feasibility of newborn dried blood spots
      for quantifying neonatal exposure at the population level.

PMID- 30219611
TI  - Early warning signals for critical transitions in cardiopulmonary health, related
      to air pollution in an urban Chinese population.
AB  - Respiratory, and cardio-cerebrovascular health-related diseases significantly
      threaten human health and together with air pollution form a complex
      pathophysiological system. Other complex biological systems show that increased
      variance and autocorrelations in time series may act as valid early warning
      signals for critical transitions. On population level, we determined the
      likelihood that increased variance and autocorrelation of hospital visit on
      cardiopulmonary disease preceded critical transitions in population health by
      human-pollution interactions. We investigated long-term hospital visits from a
      hospital in Nanjing City, China during 2006-2016 for the most important
      cardiopulmonary diseases likely to be influenced by air pollution:
      cerebrovascular accident disease (CVAD), coronary artery disease (CAD), chronic
      obstructive pulmonary disease (COPD), lung cancer disease (LCD), and the grouped
      categories of respiratory system disease (RESD) and cardio-cerebrovascular system
      disease (CCD). The time series of standard deviations (SDs) and autocorrelation
      at-lag-1 (AR-1) were studied as potential Early-Warning Indicators (EWIs) of
      transitions in population health. Elevated SDs provided an early warning for
      critical transitions in visit for LCD and overall CCD and CVAD, for the period of
      2012-2013, after which a real transition of increased visit occurred for these
      disease categories. Statistical testing showed that these SDs were significantly
      increased (p < 0.1). The long-term air pollution together with intermittent
      pollution episodes may have triggered critical transitions in population health
      for cardiopulmonary disease. It is recommended to consider significant increases
      in variability in time series of relevant system parameters, such as visit, as
      early warning signs for future transitions in populations' health states.

PMID- 30219613
TI  - Time to exonerate eyewitness memory.
AB  - Understandably enough, most people are under the impression that eyewitness
      memory is unreliable. For example, research shows that memory is malleable, so
      much so that people can come to confidently remember traumatic events that never
      actually happened. In addition, eyewitness misidentifications made with high
      confidence in a court of law are known to have played a role in more than 70% of
      the 358 wrongful convictions that have been overturned based on DNA evidence
      since 1989. However, recent research demonstrates that eyewitness confidence is
      highly indicative of accuracy on an initial, uncontaminated, properly
      administered photo lineup. In other words, low confidence indicates that the test
      result (i.e., the ID) is inconclusive, whereas high confidence indicates that the
      test result is far more conclusive. Critically, for the DNA exonerees who were
      misidentified by an eyewitness in a court of law, in every case where their
      initial confidence can be determined, the eyewitness appropriately expressed low
      confidence. For any other kind of evidence (e.g., DNA, fingerprints), an
      inconclusive test result like that would have been the end of it. By contrast, in
      the case of eyewitness evidence, investigators repeatedly tested (and therefore
      unwittingly contaminated) memory until a seemingly conclusive high-confidence ID
      could be presented to the jury. Blaming eyewitness memory for the failure of the
      criminal justice system to accept the inconclusive nature of the initial
      (uncontaminated) eyewitness evidence seems misguided. In addition to exonerating
      the innocent defendants who were wrongfully convicted, the time has come to
      exonerate eyewitness memory too.

PMID- 30219612
TI  - Diffusion-weighted MRI and ADC versus FET-PET and GdT1w-MRI for gross tumor
      volume (GTV) delineation in re-irradiation of recurrent glioblastoma.
AB  - BACKGROUND AND PURPOSE: GTV definition for re-irradiation treatment planning in
      recurrent glioblastoma (rGBM) is usually based on contrast-enhanced MRI (GdT1w
      MRI) and, for an increased specificity, on amino acid PET. Diffusion-weighted
      (DWI) MRI and ADC maps can reveal regions of high cellularity as surrogate for
      active tumor. The objective of this study was to compare the localization and
      quality of diffusion restriction foci (GTV-ADClow) with FET-PET (GTV-PET) and
      GdT1w-MRI (GTV-GdT1w-MRI). MATERIAL AND METHODS: We prospectively evaluated 41
      patients, who received a fractionated stereotactic re-irradiation for rGBM. GTV
      PET was generated automatically (tumor-to-background ratio 1.7-1.8) and manually
      customized. GTV-ADClow was manually defined based on DWI data (3D diffusion
      gradients, b = 0, 1000 s/mm2) and parametric ADC maps. The localization of
      recurrence was correlated with initial GdT1w-MRI and PET data. RESULTS: In 30/41
      patients, DWI-MRI showed areas with restricted diffusion (mean ADC-value 0.74 +/-
      0.22 mm2/s). 66% of GTVs-ADClow were located outside the GdT1w-MRI volume and 76%
      outside increased FET uptake regions. Furthermore, GTVs-ADClow were only
      partially included in the high dose volume and received in mean 82% of the
      reference dose. An adjusted volume including GdT1w-MRI, PET-positive and
      restricted diffusion areas would imply a GTV increase of 48%. GTV-PET and GdT1w
      MRI correlated better with the localization of re-recurrence in comparison to GTV
      ADClow. CONCLUSION: Unexpectedly, GTV-ADClow overlapped only partially with FET
      PET and GdT1w-MRI in rGBM. Moreover, GTV-ADClow correlated poorly with later rGBM
      recurrences. Seeing as a restricted diffusion is known to correlate with
      hypercellularity, this imaging discrepancy could only be further explained in
      histopathological studies.

PMID- 30219614
TI  - Distal radial arterial hypertrophy after transradial intervention: A serial
      intravascular ultrasound study.
AB  - BACKGROUND: Transradial intervention (TRI) may cause damage to the radial artery
      (RA). We have demonstrated intima-media thickening and luminal narrowing of the
      distal RA after TRI using intravascular ultrasound (IVUS). This study aimed to
      determine the predictors of intima-media thickening of RA after TRI in the same
      patients using serial IVUS. METHODS AND RESULTS: We enrolled 110 consecutive
      patients who underwent TRI. IVUS of RA was immediately performed after TRI and
      repeated 6 months later. Volumetric analyses were performed for the distal RA.
      The intima-media volume (IMV) increased from 53.56+/-10.85mm3 to 58.70+/-13.04mm3
      (p=0.0022), whereas the lumen volume (LV) decreased from 146.87+/-40.53mm3 to
      129.64+/-45.78mm3 (p=0.0018) and vessel volume (VV) decreased from 201.23+/
      44.55mm3 to 188.34+/-52.25mm3 (p=0.0306). Multiple regression analysis revealed
      diabetes as the most powerful independent predictor of the percentage change in
      IMV of the distal RA after TRI. The percentage change in IMV significantly
      increased in the DM group compared with non-DM group (p<0.001). The percentage
      change in IMV was significantly positively correlated with HbA1c. CONCLUSIONS:
      Serial IVUS of the distal RA revealed a significant increase in IMV and decreases
      in LV and VV. Diabetes was the most powerful independent predictor of the
      percentage change in IMV of the distal RA after TRI. The percentage change in IMV
      was significantly positively correlated with HbA1c.

PMID- 30219615
TI  - Denver Emergency Department Trauma Organ Failure Score predicts healthcare
      resource utilization in adult trauma patients.
AB  - BACKGROUND: Early identification of trauma patients who need specialized
      healthcare resources may facilitate goal-directed resuscitation and effective
      secondary triage. OBJECTIVE: To estimate associations between Denver Emergency
      Department (ED) Trauma Organ Failure (TOF) Score and healthcare resource
      utilization. METHODS: Retrospective study of adult trauma patients at Denver
      Health Medical Center. The outcome was resource utilization including: intensive
      care unit (ICU) length of stay (LOS), hospital LOS, procedures, and costs.
      Multivariable regression analyses were used to estimate associations between
      moderate- or high-risk patients, as determined by the Denver ED TOF Score, and
      healthcare resource utilization. RESULTS: We included 3000 patients with a median
      age of 42 (IQR 27-56) years, 71% male, median injury severity score 9 (IQR 5-16),
      and 83% blunt mechanism. Among the cohort, 1379 patients (46%) were admitted to
      the ICU and 122 (4%) died. The adjusted relative risk for high- and moderate-risk
      as compared to low risk for number of procedures performed was 2.31 (95% CI 2.07
      2.57) and 1.80 (95% CI 1.59-2.03) respectively; ICU LOS was 2.87 (95% CI 2.70
      3.05) and 1.71 (95% CI 1.60-1.83) respectively; hospital LOS was 3.33 (95% CI
      3.21-3.45) and 1.97 (95% CI 1.90-2.05) respectively. The adjusted geometric mean
      for high-, moderate-, and low-risk for costs was $48,881 (95% CI $43,799
      $54,552), $27,890 (95% CI $25,460-$30,551), and $12,983 (95% CI $12,493-$13,492),
      respectively. CONCLUSIONS: The Denver ED TOF Score predicts healthcare resource
      utilization, and is a useful bedside tool to identify patients early after injury
      that are likely to require significant healthcare resources and specialized
      trauma care.

PMID- 30219616
TI  - An unusual cause of shoulder pain and weakness.
AB  - Shoulder pain and weakness are common presenting Emergency Department complaints.
      Patients are often diagnosed with fractures, dislocations, bursitis, and muscle
      strain. Here we present an unusual cause of shoulder pain in an athletic and
      otherwise healthy young patient that does not respond to typical treatments for
      musculoskeletal pain.

PMID- 30219618
TI  - Erector spinae block at L2 for thigh lift surgery, a new application.

PMID- 30219619
TI  - Pericapsular nerve group (PENG) block is effective for dislocation of the hip
      joint.

PMID- 30219617
TI  - Early changes in white matter predict intellectual outcome in children treated
      for posterior fossa tumors.
AB  - PURPOSE: Prospective and longitudinal neuroimaging studies of posterior fossa
      tumors are scarce. Here we evaluate the early changes in white matter and
      intellectual outcome up to 3 years after diagnosis. PATIENTS AND METHODS: Twenty
      two children with posterior fossa tumors and 24 similarly-aged healthy children
      participated. Patients included: (a) 12 individuals who received surgery, cranial
      spinal radiation (CSR), and focal radiation to the tumor bed (CSR group) and (b)
      10 individuals who received local therapy, either surgery only or surgery and
      focal radiation to the tumor bed (Local group). Diffusion tensor imaging (DTI)
      and intelligence measures were obtained an average of 3 months after diagnosis
      and then at 12, 24, and 36 months later. DTI tractography and voxel-wise
      approaches were employed. The Neurological Predictor Scale was used to summarize
      the type and amount of treatment for PF tumor patients. Linear mixed modelling
      was used to evaluate group differences at baseline and changes over time in DTI
      metrics for both the specific white matter tracts and voxel-wise, as well as for
      intelligence measures. RESULTS: Based on tractography, patients treated with CSR
      had significantly higher Axial and Mean diffusivity in the cortical-spinal tracts
      (CST) 3 month after diagnosis - particularly on the right side, p < .003,
      compared to healthy children. Mean diffusivity in right CST decreased over time
      in this group of patients, p = .001. No differences compared to controls were
      evident in specific tracts for the Local group, p > .10. Voxel-wise analyses
      revealed multiple areas of white matter compromise in both patients groups.
      Notably, both patient groups had lower scores on intelligence measures compared
      to the Control group: The CSR group displayed lower performance 3 months
      following diagnosis, ps < 0.001, and their performance remained stable over time
      ps > 0.10, whereas the Local group displayed no differences at 3 months, ps>
      0.10, but their performance declined over time, ps < 0.01. At baseline, higher MD
      in right CST predicted lower Perceptual Reasoning scores across all participants,
      p = .001. Furthermore, lower FA in left IFOF at baseline predicted decline in
      Processing Speed over time, p = .001. In patients, more aggressive treatment
      protocols and presence of mutism were related to lower performance on
      intelligence measures at baseline, ps < 0.04. CONCLUSIONS: Children treated with
      CSR displayed diffuse white matter compromise and poor intellectual outcome
      shortly after radiation treatment. There was evidence of subsequent growth of
      white matter structure, but stable intellectual insult. Conversely, in children
      treated with either surgery only or surgery and focal radiation to the tumor bed
      we observed less compromise of white matter early following treatment and no
      intellectual insult compared to healthy children. However, declines in
      intellectual function were evident for these children, though their performance
      remained within the average normative range. Overall, results suggest that early
      intervention is necessary to circumvent these deficits.

PMID- 30219620
TI  - Advanced practice in case management: An essential element in the new complex
      chronicity care model.
AB  - The increased prevalence of complex chronic diseases in all stages of life, the
      progressive aging of the population, the prevalence of multimorbidity,
      polypharmacy, and loss of autonomy, have given rise to new needs in society. The
      current model of care is failing to meet these needs in an effective or
      sustainable way. People with complex chronic diseases are vulnerable, they
      deteriorate as diseases progress, and they require individualized and coordinated
      professional care that takes into account the progression of the disease,
      transitions and people's preferences. It is essential to determine a new care
      paradigm as a framework for the projects and actions that should be promoted to
      reach transversal, sustainable and quality care directed at people with complex
      and advanced chronic diseases in all stages of life. Different studies show that
      case management is an added value in terms of quality, safety and cost
      effectiveness. However, its implementation in Spain is uneven and heterogeneous,
      and no regulations have yet been developed to give stability to this new nurse
      figure. The Ministry and the Autonomous Communities now have the responsibility
      to create regulations and institutionalize the figure of case management
      nurses/advanced practice nurses, with a clear definition of their professional
      competences and functions, as has been done in other countries.

PMID- 30219621
TI  - Correlating efficacy and immunogenicity in malaria vaccine trials.
AB  - The availability of an effective and appropriately implemented malaria vaccine
      would form a crucial cornerstone of public health efforts to fight this disease.
      Despite many decades of research, however, no malaria vaccine has yet shown
      satisfactory protective efficacy or been rolled-out. Validated immunological
      substitute endpoints have the potential to accelerate clinical vaccine
      development by reducing the required complexity, size, duration and cost of
      clinical trials. Besides facilitating clinical development of existing vaccine
      candidates, understanding immunological mechanisms of protection may drive the
      development of fundamentally new vaccination approaches. In this review we focus
      on correlates of protection in malaria vaccine development: Does immunogenicity
      predict malaria vaccine efficacy and why is this question particularly difficult?
      Have immunological correlates accelerated malaria vaccine development in the past
      and will they facilitate it in the future? Does Controlled Human Malaria
      Infection represent a valid model for identifying such immunological correlates,
      or a correlate of protection against naturally-acquired malaria in itself?

PMID- 30219622
TI  - Renal denervation in hypertension: Towards a true revival?

PMID- 30219624
TI  - Cognitive and upper limb symptom changes from a tap test in Idiopathic Normal
      Pressure Hydrocephalus.
AB  - OBJECTIVES: To determine which cognitive and upper limb assessments can identify
      change in patients undergoing a Cerebrospinal fluid (CSF) tap test (TT) diagnosed
      with idiopathic Normal Pressure Hydrocephalus (iNPH). PATIENTS AND METHODS:
      Prospective observational study of 74 iNPH patients undergoing a CSF TT for
      consideration of a ventricular peritoneal shunt. Patients who were offered
      surgical intervention were classified as responders. Patients were assessed with
      a battery of cognitive and upper limb assessments prior to and following a CSF
      TT. The Timed up and go cognition (TUG-C), Montreal Cognitive assessment (MoCA)
      and 9-hole peg test were utilised. RESULTS: 40 patients were classified
      responders. Significant differences were identified for responders for the MoCA
      (0.62 points) and TUG-C (-6.02 s). Only the executive function and orientation
      sub scores of the MoCA showed significant changes for responders. The 9 hole peg
      test mean change of 4.33 s for responders was not significant. Non-responder
      change scores for the MoCA (0.22 points), TUG-C (0.3 s) and 9 hole peg test (2.58
      s) were not significant. CONCLUSION: The TUG-C has the potential to identify
      change in patients resulting from a CSF TT. While statistically significant
      change was found for the MoCA, a mean change of less than 1 point on this scale
      is unlikely to be clinically relevant. Similarly, the 9 hole peg test cannot be
      endorsed as an assessment tool for identifying changed performance in iNPH.

PMID- 30219623
TI  - Kinetic change of spinal cord compression on flexion-extension magnetic resonance
      imaging in cervical spine.
AB  - OBJECTIVE: We aimed to determine the changes in cervical canal diameters and
      spinal cord compression at each level from C2-3 to C7-T1 in flexion and extension
      positions and to study the use of flexion-extension magnetic resonance imaging
      (MRI). We also aimed to assess the changes in the length of the spinal cord in
      flexion and extension positions of the cervical spine. PATIENTS AND METHODS:
      Flexion-extension MRI scans were performed consecutively on sixty-six patients
      with neck pain with/without neurogenic symptoms of the cervical spine. All
      patients were treated conservatively. We investigated the length of the cervical
      spinal cord (LSC), length of the cervical spinal anterior column (LAC), length of
      the cervical spinal posterior column (LPC), spinal canal diameter, and severity
      of cord compression in flexion, neutral, and extension positions. RESULTS: At
      each intervertebral level (from C2-3 to C7-T1), the average spinal canal diameter
      showed significant decrease from flexion to extension positions (P < 0.05). The
      average LSC, LAC, and LPC were decreased on extension of the neck compared with
      flexion (P < 0.05). Higher stages were found in extension position than in
      flexion position with statistically significant differences (P < 0.05).
      CONCLUSION: The use of flexion-extension MRI may demonstrate true pathology that
      contributes in the pathogenesis of cervical degenerative disease (CDD). Higher
      stages in spinal cord compression were found in extension position than in
      flexion position. However, higher stages in spinal cord compression in extension
      position did not necessarily cause severe myelopathy. This finding is an
      important evidence for conservative therapy on patient neck position education.

PMID- 30219625
TI  - Encorafenib plus binimetinib: an embarrassment of riches.

PMID- 30219627
TI  - Cancer trends and disparities in India: data needs for providing equitable cancer
      care.

PMID- 30219626
TI  - The burden of cancers and their variations across the states of India: the Global
      Burden of Disease Study 1990-2016.
AB  - BACKGROUND: Previous efforts to report estimates of cancer incidence and
      mortality in India and its different parts include the National Cancer Registry
      Programme Reports, Sample Registration System cause of death findings, Cancer
      Incidence in Five Continents Series, and GLOBOCAN. We present a comprehensive
      picture of the patterns and time trends of the burden of total cancer and
      specific cancer types in each state of India estimated as part of the Global
      Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 because such a
      systematic compilation is not readily available. METHODS: We used all accessible
      data from multiple sources, including 42 population-based cancer registries and
      the nationwide Sample Registration System of India, to estimate the incidence of
      28 types of cancer in every state of India from 1990 to 2016 and the deaths and
      disability-adjusted life-years (DALYs) caused by them, as part of GBD 2016. We
      present incidence, DALYs, and death rates for all cancers together, and the
      trends of all types of cancers, highlighting the heterogeneity in the burden of
      specific types of cancers across the states of India. We also present the
      contribution of major risk factors to cancer DALYs in India. FINDINGS: 8.3% (95%
      uncertainty interval [UI] 7.9-8.6) of the total deaths and 5.0% (4.6-5.5) of the
      total DALYs in India in 2016 were due to cancer, which was double the
      contribution of cancer in 1990. However, the age-standardised incidence rate of
      cancer did not change substantially during this period. The age-standardised
      cancer DALY rate had a 2.6 times variation across the states of India in 2016.
      The ten cancers responsible for the highest proportion of cancer DALYs in India
      in 2016 were stomach (9.0% of the total cancer DALYs), breast (8.2%), lung
      (7.5%), lip and oral cavity (7.2%), pharynx other than nasopharynx (6.8%), colon
      and rectum (5.8%), leukaemia (5.2%), cervical (5.2%), oesophageal (4.3%), and
      brain and nervous system (3.5%) cancer. Among these cancers, the age-standardised
      incidence rate of breast cancer increased significantly by 40.7% (95% UI 7.0
      85.6) from 1990 to 2016, whereas it decreased for stomach (39.7%; 34.3-44.0), lip
      and oral cavity (6.4%; 0.4-18.6), cervical (39.7%; 26.5-57.3), and oesophageal
      cancer (31.2%; 27.9-34.9), and leukaemia (16.1%; 4.3-24.2). We found substantial
      inter-state heterogeneity in the age-standardised incidence rate of the different
      types of cancers in 2016, with a 3.3 times to 11.6 times variation for the four
      most frequent cancers (lip and oral, breast, lung, and stomach). Tobacco use was
      the leading risk factor for cancers in India to which the highest proportion
      (10.9%) of cancer DALYs could be attributed in 2016. INTERPRETATION: The
      substantial heterogeneity in the state-level incidence rate and health loss
      trends of the different types of cancer in India over this 26-year period should
      be taken into account to strengthen infrastructure and human resources for cancer
      prevention and control at both the national and state levels. These efforts
      should focus on the ten cancers contributing the highest DALYs in India,
      including cancers of the stomach, lung, pharynx other than nasopharynx, colon and
      rectum, leukaemia, oesophageal, and brain and nervous system, in addition to
      breast, lip and oral cavity, and cervical cancer, which are currently the focus
      of screening and early detection programmes. FUNDING: Bill & Melinda Gates
      Foundation; and Indian Council of Medical Research, Department of Health
      Research, Ministry of Health and Family Welfare, Government of India.

PMID- 30219628
TI  - Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus
      binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open
      label, randomised, phase 3 trial.
AB  - BACKGROUND: Encorafenib plus binimetinib and encorafenib alone improved
      progression-free survival compared with vemurafenib in patients with BRAFV600
      mutant melanoma in the COLUMBUS trial. Here, we report the results of the
      secondary endpoint of overall survival. METHODS: COLUMBUS was a two-part,
      randomised, open-label, phase 3 study done at 162 hospitals in 28 countries.
      Eligible patients were aged at least 18 years with histologically confirmed,
      locally advanced, unresectable, or metastatic cutaneous melanoma, or unknown
      primary melanoma, BRAFV600E or BRAFV600K mutation, an Eastern Cooperative
      Oncology Group (ECOG) performance status of 0 or 1, and were treatment naive or
      had progressed on or after first-line immunotherapy. In part 1 of the study,
      patients were randomly assigned (1:1:1) by use of interactive response technology
      to receive oral encorafenib 450 mg once daily plus oral binimetinib 45 mg twice
      daily (encorafenib plus binimetinib group), oral encorafenib 300 mg once daily
      (encorafenib group), or oral vemurafenib 960 mg twice daily (vemurafenib group).
      Randomisation was stratified by the American Joint Committee on Cancer stage,
      ECOG performance status, and BRAF mutation status. The primary outcome of the
      trial, progression-free survival with encorafenib plus binimetinib versus
      vemurafenib, was reported previously. Here we present the prespecified interim
      overall survival analysis. Efficacy analyses were by intent to treat. Safety was
      analysed in patients who received at least one dose of study drug. Part 2 of the
      study was initiated at the request of the US Food and Drug Administration to
      better understand the contribution of binimetinib to the combination therapy by
      comparing encorafenib 300 mg once daily plus binimetinib 45 mg twice daily with
      encorafenib 300 mg once daily alone. Results of part 2 will be published
      separately. This trial is ongoing and is registered with ClinicalTrials.gov,
      number NCT01909453, and EudraCT, number 2013-001176-38. FINDINGS: Between Dec 30,
      2013, and April 10, 2015, 577 of 1345 screened patients were randomly assigned to
      receive encorafenib plus binimetinib (n=192), encorafenib (n=194), or vemurafenib
      (n=191). Median follow-up for overall survival was 36.8 months (95% CI 35.9
      37.5). Median overall survival was 33.6 months (95% CI 24.4-39.2) with
      encorafenib plus binimetinib and 16.9 months (14.0-24.5) with vemurafenib (hazard
      ratio 0.61 [95% CI 0.47-0.79]; two-sided p<0.0001). The most common grade 3 or 4
      adverse events did not change substantially from the first report; those seen in
      more than 5% of patients treated with encorafenib plus binimetinib were increased
      gamma-glutamyltransferase (18 [9%] of 192 patients), increased blood creatine
      phosphokinase (14 [7%]), and hypertension (12 [6%]); those seen with encorafenib
      alone were palmar-plantar erythrodysaesthesia syndrome (26 [14%] of 192
      patients), myalgia (19 [10%]), and arthralgia (18 [9%]); and with vemurafenib the
      most common grade 3 or 4 adverse event was arthralgia (11 [6%] of 186 patients).
      One death in the combination treatment group was considered by the investigator
      to be possibly related to treatment. INTERPRETATION: The combination of
      encorafenib plus binimetinib provided clinically meaningful efficacy with good
      tolerability as shown by improvements in both progression-free survival and
      overall survival compared with vemurafenib. These data suggest that the
      combination of encorafenib plus binimetinib is likely to become an important
      therapeutic option in patients with BRAFV600-mutant melanoma. FUNDING: Array
      BioPharma, Novartis.

PMID- 30219629
TI  - Clinical Implications of Basilar Artery Plaques in the Pontine Infarction with
      Normal Basilar Angiogram: A High-Resolution Magnetic Resonance Imaging Study.
AB  - BACKGROUND: Using high-resolution magnetic resonance imaging (HR-MRI), we
      investigated the impact of basilar artery plaques that were not detected by
      magnetic resonance angiography (MRA) on the functional outcomes of patients with
      acute pontine infarction. METHODS: A total of 40 patients with acute pontine
      infarction and normal basilar findings on MRA prospectively underwent HR-MRI for
      detection of basilar artery plaques. A relevant plaque was defined as one on the
      dorsal side of basilar artery, the same side of the ischemic lesion, and the same
      axial slices of the ischemic lesion. We analyzed the relationship between the
      relevant basilar artery plaques and the functional outcomes at 3 months. RESULTS:
      The initial National Institutes of Health Stroke Scale score (3.5 versus 2.0, P =
      .012), and the incidences of neurological deterioration (42.9% versus 6.3%, P =
      .031) and unfavorable functional outcome (71.4% versus 12.5%, P = .001) were
      higher in patients with relevant basilar artery plaques than in those without. On
      multiple regression analysis, the relevant basilar artery plaque was a
      significant and independent predictor of unfavorable functional outcome (odds
      ratio, 6.662; 95% confidence interval, 1.117-39.735; P = .037). CONCLUSIONS: The
      presence of a relevant basilar artery plaque was closely related with unfavorable
      functional outcome in patients with acute pontine infarction even if the
      patients' MRA showed normal basilar findings.

PMID- 30219630
TI  - Impact of Plaque Composition on Risk of Coronary Artery Diseases in Patients with
      Carotid Artery Stenosis.
AB  - OBJECT: Recent clinical studies have recently demonstrated a strong association
      between carotid artery stenosis and coronary artery disease (CAD). However, the
      clinical impact of carotid plaque composition on CAD remains unclear. This study
      was aimed to determine the relationship between carotid plaque composition and
      CAD in patients who underwent carotid endarterectomy (CEA) or carotid artery
      stenting (CAS). METHODS: This prospective cohort study included a total of 97
      patients who were admitted to our institution between January 2012 and April
      2016. Magnetic resonance (MR) imaging was performed to semi-quantitatively
      analyze the components of carotid plaques by calculating the ratio of plaque
      intensity to muscle intensity on T1-weighted image. Diagnosis of CAD was based on
      patient history and clinical examinations during preoperative, postoperative and
      follow-up periods. Multivariate logistic analysis was performed to determine the
      risk factors for CAD. The relationship between contralateral plaque composition
      and CAD was also investigated. RESULTS: Of 97 patients, 33 were diagnosed as
      having 44 episodes of CAD. Multivariate logistic analysis revealed that ASO (odds
      ratio [OR], 5.7; 95% confidence interval [CI], 1.8-18.9), contralateral carotid
      occlusive disease (OR, 6.5; 95%CI, 1.7-22.9), and plaque/muscle ratio (OR, 3.0;
      95%CI, 1.4-10.1) were independent factors for predicting CAD. The patients
      diagnosed as having CAD during the follow-up period had significantly higher
      plaque/muscle ratio than those with CAD on preoperative evaluations (2.29 +/-
      .21vs. 1.97 +/- .33, P < .01). CONCLUSIONS: This study clearly demonstrates that
      ASO, contralateral carotid artery stenosis, and high-intensity carotid plaque on
      T1-weighted MRI independently predict CAD. Contralateral carotid plaque
      composition was also associated with concomitant CAD. Moreover, high-intensity
      carotid plaque may predict the future development of CAD. Therefore, unstable
      carotid plaque should be considered as the clinical phenotype of systemic
      inflammation and a novel, robust marker for future CAD.

PMID- 30219631
TI  - Aicardi goutieres syndrome is associated with pulmonary hypertension.
AB  - While pulmonary hypertension (PH) is a potentially life threatening complication
      of many inflammatory conditions, an association between Aicardi Goutieres
      syndrome (AGS), a rare genetic cause of interferon (IFN) overproduction, and the
      development of PH has not been characterized to date. We analyzed the cardiac
      function of individuals with AGS enrolled in the Myelin Disorders Bioregistry
      Project using retrospective chart review (n = 61). Additional prospective
      echocardiograms were obtained when possible (n = 22). An IFN signature score, a
      marker of systemic inflammation, was calculated through the measurement of mRNA
      transcripts of type I IFN-inducible genes (interferon signaling genes or ISG).
      Pathologic analysis was performed as available from autopsy samples. Within our
      cohort, four individuals were identified to be affected by PH: three with
      pathogenic gain-of-function mutations in the IFIH1 gene and one with heterozygous
      TREX1 mutations. All studied individuals with AGS were noted to have elevated IFN
      signature scores (Mann-Whitney p < .001), with the highest levels in individuals
      with IFIH1 mutations (Mann-Whitney p < .0001). We present clinical and histologic
      evidence of PH in a series of four individuals with AGS, a rare interferonopathy.
      Importantly, IFIH1 and TREX1 may represent a novel cause of PH. Furthermore,
      these findings underscore the importance of screening all individuals with AGS
      for PH.

PMID- 30219633
TI  - Now or future? Analyzing the effects of message frame and format in motivating
      Chinese females to get HPV vaccines for their children.
AB  - OBJECTIVE: This study aims to examine the impacts of gain vs. loss-framed
      messages and narrative messages on Chinese women's intentions to get HPV vaccines
      for their children. METHODS: A survey experiment was conducted among Chinese
      females (N = 453) assessing their responses to 3 types of messages (i.e. gain
      framed, loss-framed and narrative) designed to promote HPV vaccination. RESULTS:
      No main effect was found for message types, but loss-framed message slightly
      increased vaccination intention. Time orientation moderated the relationship
      between message framing and vaccination intention. CONCLUSION: Narrative message
      works better among present-minded individuals, whereas gain-framed message was
      more persuasive for future-minded individuals. Integration of message frames
      (gain vs. loss) and message type (narrative vs. non-narrative) is recommended for
      future research. PRACTICE IMPLICATIONS: Narrative persuasion could be an
      effective tool in promoting health behaviors especially among present-minded
      individuals, or when the consequences of health decisions are temporally distant.

PMID- 30219632
TI  - Anthocyanic pigments from elicited in vitro grown shoot cultures of Vaccinium
      corymbosum L., cv. Brigitta Blue, as photosensitizer in natural dye-sensitized
      solar cells (NDSSC).
AB  - We investigated the effect on anthocyanins and total phenols content and
      antioxidant capacity of in vitro shoot cultures of Vaccinium corymbosum L., cv.
      Brigitta Blue, grown on an eliciting medium supplied with 10 MUM naphthalene
      acetic acid, in combination with reduced content of salts and organics in respect
      to the basal medium. After 45 days, higher content of total phenols and
      anthocyanins was obtained from extracts of shoots grown on the elicitation
      medium. Anthocyanin molecules, absent in control shoots, were identified by HPLC
      MS as delphinidine-glycoside, cyanidine-glycoside, delphinidine-arabinoside,
      cyanidine- arabinoside and cyanidine-acetylglycoside. Chlorogenic acid, present
      in control shoots, was nearly absent in elicited shoots. We exploited the
      anthocyanin - based raw extracts of "Brigitta Blue" shoots grown on the
      elicitation medium as a source of natural dye photosensitizers for Dye Sensitized
      Solar Cells, taking into account that such raw extracts showed antioxidant
      properties and photostability features. A purified dye was also prepared and the
      comparison of the latter with the raw one has been analysed by
      spectrophotometric, chromatographic and power conversion efficiency
      determination. The power conversion efficiencies from the raw and the purified
      dye were not different and they were comparable to the data obtained by other
      authors with anthocyanin-based dyes from in vivo grown plants.

PMID- 30219634
TI  - Patient education and engagement in postoperative pain management decreases
      opioid use following knee replacement surgery.
AB  - OBJECTIVE: Effects of patient education on perioperative analgesic utilization
      are not well defined. We designed a simple pain management educational card for
      total knee arthroplasty (TKA) patients and retrospectively reviewed clinical data
      before and after implementation to test the hypothesis that more informed
      patients will use less opioid. METHODS: With IRB approval, we analyzed clinical
      data collected perioperatively on all TKA patients one month before (PRE) and one
      month after (POST) card implementation. The card was designed using a modified
      Delphi method; the front explained all analgesic medications and the Defense and
      Veterans Pain Rating Scale was on the back. The primary outcome was total opioid
      dosage in morphine milligram equivalents (MME) for the first two postoperative
      days. Secondary outcomes included daily opioid usage, pain scores, ambulation
      distance, hospital length of stay and use of antiemetics. RESULTS: There were 20
      patients in each group with no differences in baseline characteristics. Total two
      day MME [median (10th-90th percentiles)] was 71 (32-285) for PRE and 38 (1-117)
      for POST (p = 0.001). There were no other differences. CONCLUSION: Educating TKA
      patients in multimodal pain management using a simple tool decreases opioid
      usage. PRACTICE IMPLICATIONS: Empowering TKA patients with education can reduce
      opioid use perioperatively.

PMID- 30219635
TI  - Are visual processes causally involved in "perceptual simulation" effects in the
      sentence-picture verification task?
AB  - Many studies have shown that sentences implying an object to have a certain shape
      produce a robust reaction time advantage for shape-matching pictures in the
      sentence-picture verification task. Typically, this finding has been interpreted
      as evidence for perceptual simulation, i.e., that access to implicit shape
      information involves the activation of modality-specific visual processes. It
      follows from this proposal that disrupting visual processing during sentence
      comprehension should interfere with perceptual simulation and obliterate the
      match effect. Here we directly test this hypothesis. Participants listened to
      sentences while seeing either visual noise that was previously shown to strongly
      interfere with basic visual processing or a blank screen. Experiments 1 and 2
      replicated the match effect but crucially visual noise did not modulate it. When
      an interference technique was used that targeted high-level semantic processing
      (Experiment 3) however the match effect vanished. Visual noise specifically
      targeting high-level visual processes (Experiment 4) only had a minimal effect on
      the match effect. We conclude that the shape match effect in the sentence-picture
      verification paradigm is unlikely to rely on perceptual simulation.

PMID- 30219636
TI  - The Marathon of Life: From Near-Death by Avalanche to Ultra-Trail Run.

PMID- 30219637
TI  - Salivary proteome patterns of individuals exposed to High Altitude.
AB  - OBJECTIVE: Identification of molecular signatures having key roles in hypobaric
      hypoxia by analysing the salivary proteome. Saliva holds a promising future in
      the search for new clinical biomarkers that are easily accessible, less complex,
      accurate, and cost effective as well as being non-invasive. METHODOLOGY: We
      employed qualitative proteomics approach to develop discriminatory biomarker
      signatures from human saliva exposed to hypobaric hypoxia. Salivary proteins were
      analyzed and compared between age-matched healthy subjects exposed to high
      altitude (~13700 ft) for seven days (HAD7) with control subjects at sea level
      (Normoxia) by using 2-Dimensional gel electrophoresis/Mass Spectrometry approach.
      RESULTS: Several proteins with significant differential expression were found.
      The up-regulated proteins were apoptosis inducing factor-2, cystatin S, cystatin
      SN and carbonic anhydrase 6. The down regulated proteins were polymeric
      immunoglobulin receptor, alpha-enolase and prolactin-inducible protein. Further
      confirmation of the altered proteins such as alpha enolase, carbonic anhydrase 6,
      prolactin-inducible protein, apoptosis inducing factor 2, cystatin S and cystatin
      SN were performed using immunoblotting. The expression patterns of the selected
      proteins observed by immunoblot were in concurrence with 2-Dimesional gel
      electrophoresis results, therefore affirming the authenticity of the proteomic
      investigation. CONCLUSION: This study provides the proof of concept of salivary
      biomarkers for the non-invasive detection of hypobaric hypoxia induced effects.
      It is highly feasible to turn these biomarkers into an applicable clinical test
      after large scale validation.

PMID- 30219638
TI  - Pre- and probiotic overview.
AB  - The dynamic relationship between gut microbiota and its human host is also known
      as a trophic association that might range from commensalism, where only the
      microbe enjoys a positive effect from the relationship, to intestinal symbiosis
      where both host and microbe benefit from their interaction. In the last years, we
      have started to understand how alterations of the gut microbiota composition
      leading to the disruption of host-microbial interactions are associated and/or
      predispose individuals to disease conditions ranging from inflammatory bowel
      diseases to allergy and functional gastrointestinal disorders, such as irritable
      bowel syndrome. While we await important insights in this field, the microbiota
      is already a therapeutic target. Based on the actual definitions, prebiotics are
      defined as substrates that are selectively utilized by host microorganisms
      conferring a health benefit, while probiotics are live microorganisms that, when
      administered in adequate amounts, confer a health benefit on the host. Although
      their health promoting activities encompasses numerous effects, including
      immunostimulation, competitive exclusion of pathogens, and gut barrier
      enhancement, the exact mechanism of action by which these compounds exert their
      beneficial actions in humans is only partially known. In this review, we
      highlight the current insights into the clinical applications of prebiotics and
      probiotics in gastroenterology.

PMID- 30219640
TI  - Retinal microvascular dysfunction in hypercholesterolemia.
AB  - BACKGROUND: Hypercholesterolemia is one of the most important contributors to
      atherosclerosis. Whether hypercholesterolemia also affects the retinal
      microcirculation is unclear. OBJECTIVE: The goal of our study was to assess the
      association of cholesterol levels with retinal microvascular function using
      dynamic and static retinal vessel analysis (RVA) in a primary prevention setting.
      METHODS: This cross-sectional, observational study prospectively recruited 67
      patients with hypercholesterolemia without known cardiovascular disease (mean age
      64.4 +/- 10.4 years; 45% female) and 78 healthy controls (mean age 61.8 +/- 11.2
      years; 45% female). The primary end point of the study was flicker-induced
      dilatation of retinal arterioles (FIDart) with secondary exploratory outcomes
      including venular FID (FIDven), arteriovenous ratio, flow-mediated dilatation and
      arterial stiffness as measured with augmentation index and pulse wave velocity.
      Multiple regression analysis was performed to study the association of
      cholesterol levels with retinal microvascular function. RESULTS: FIDart was
      significantly impaired in patients with hypercholesterolemia compared with
      healthy controls (mean FIDart 2.1 +/- 1.8 vs 3.1 +/- 1.8%, P = .001). This
      association remained when analysis was restricted to dyslipidemic patients
      without coexisting hypertension or lipid-lowering therapy. No significant
      differences remained for FIDven, flow-mediated dilatation, arteriovenous ratio,
      or arterial stiffness between the groups. Low-density lipoprotein, but not high
      density lipoprotein, cholesterol was a significant negative predictor of FIDart
      in multiple regression analysis. CONCLUSION: Hypercholesterolemia is associated
      with significant retinal microvascular dysfunction as evidenced by a reduction in
      flicker-induced dilatation of retinal arterioles. Dynamic RVA may be a promising
      method for the study of retinal microvascular dysfunction in populations at
      elevated cardiovascular risk.

PMID- 30219639
TI  - Salivary C-reactive protein among at-risk adolescents: A methods investigation of
      out of range immunoassay data.
AB  - Inflammatory markers including C-Reactive Protein (CRP) are increasingly used
      within research and clinical settings. Yet, varying methodologies for cleaning
      immunoassay data with out of range (OOR) samples may alter characteristic levels
      of CRP, thereby obscuring interpretation and reliability. This study investigated
      the influence of eight immunoassay OOR data treatment techniques on salivary CRP
      (sCRP) samples from at-risk adolescents. Participants from the 'Sleep and
      Education: learning New Skills Early' (SENSE) Study were 86 adolescents at-risk
      for depression (50 female), aged 14.29 years (SD = 1.04). ANOVA results showed no
      statistically significant differences in average morning (F(7, 590) = 1.24, p =
      .28) and evening (F(7, 599)=1.29, p = .25) values produced by each OOR data
      cleaning technique. However, varying techniques produced differences in the
      magnitude of Pearson's correlations between consecutive saliva samples (r's
      between 0.27-0.78), and influenced the significance of a sCRP diurnal pattern;
      two techniques produced statistically higher morning than evening sCRP levels
      (t(85) = 2.70, p = .01 and t(85) = 2.67, p = .01), whereas six techniques failed
      to find statistical differences between morning and evening sCRP levels (p's
      >.05). Varying techniques also produced statistically divergent associations
      between sCRP and age and depressive symptoms. Results from this study provide
      evidence for the temporal stability of sCRP among adolescents, show winsorization
      as an effective OOR data management technique, and highlight the influence of
      methodological decisions in cleaning salivary biomarker data and the need for
      consistency within the field.

PMID- 30219641
TI  - Differences in heme and hemopexin content in lipoproteins from patients with
      sickle cell disease.
AB  - BACKGROUND: High blood cholesterol is associated with atherogenesis and
      endothelial dysfunction. The latter is present in hemolytic diseases, such as
      sickle cell anemia, whose carriers have hypocholesterolemia and low incidence of
      coronary artery disease. OBJECTIVE: We aimed to characterize cholesterol
      fractions in patients with sickle cell disease and explore the relationship among
      lipoproteins, varying degrees of hemolysis, and its biomarkers. METHODS: We
      recruited 37 healthy individuals, 39 with hemoglobin SC disease, and 40 with
      sickle cell anemia and quantified cholesterol fractions, heme resulting from
      hemoglobin breakdown, and its main scavenger protein hemopexin. RESULTS:
      Hypocholesterolemia was most significant in patients with sickle cell anemia, and
      cholesterol levels correlated positively with hemopexin. Nevertheless, patients
      still had higher relative low-density lipoprotein (LDL) oxidation than healthy
      subjects. Analysis of lipoproteins isolated by density ultracentrifugation showed
      that the LDL fraction contained higher concentrations of heme than the high
      density lipoprotein (HDL) fraction, whereas HDL contained more hemopexin than
      LDL, albeit greatly reduced in patients. CONCLUSION: Our findings show that the
      abnormally low lipoprotein levels in sickle cell anemia correlate with hemolysis
      markers, particularly with hemopexin concentrations, along with significant
      reduction of this heme scavenger in HDL fractions. This may suggest an important
      role for HDL in the defense against heme-induced endothelial dysfunction in
      hemolytic diseases.

PMID- 30219642
TI  - Recommendations for Perioperative Management in Patients With Absent Right
      Superior Vena Cava.

PMID- 30219643
TI  - Myasthenia Gravis and Thymoma Surgery: A Clinical Update for the Cardiothoracic
      Anesthesiologist.
AB  - Myasthenia gravis (MG) is a rare neuromuscular disorder characterized by skeletal
      muscle weakness. Patients with MG who have thymoma and thymic hyperplasia have
      indications for thymectomy. The perioperative care of patients with MG scheduled
      for thymus resection should be focused on optimizing their neuromuscular
      function, identifying factors related to postoperative mechanical ventilation,
      and avoiding of triggers associated with myasthenic or cholinergic crisis.
      Minimally invasive surgical techniques, use of regional analgesia, and avoidance
      or judicious administration of neuromuscular blocking drugs (NMBs) is recommended
      during the perioperative period. If NMBs are used, sugammadex appears to be the
      drug of choice to restore adequately the neuromuscular transmission. In patients
      with postoperative myasthenic crisis, plasma exchange or intravenous immune
      globulin and mechanical support is recommended.

PMID- 30219644
TI  - Creation and validation of a scale of sexuality for adolescents: Scale of Myths
      about Sexuality.
AB  - INTRODUCTION: In recent decades western countries have become more open about
      sexuality and sexual relations, and adolescents get information about these
      issues mainly through the internet, TV and social networks. Often such
      information is incomplete, wrong or even contradicts itself. What favors them to
      develop myths, false beliefs and/or negative attitudes about sexuality, love,
      equality in relationships, or Sexually Transmitted Infections. At the same time,
      the presence of myths favors double standards, sexism, and a negative attitude
      toward toward personal, partner and/or social sexuality. OBJECTIVES: To create a
      scale for evaluating the permanence of myths about sexuality in adolescents, and
      to analyze the structural reliability and validity of this scale. METHOD: The
      sample was formed by a pilot group (n=216) and a final group (n=661), both with
      adolescents from high schools in the province of Malaga, obtained by non
      probability cluster sampling. The first 69 initial items were given to the pilot
      sample to determine the final questions making up the "Escala de Mitos sobre la
      Sexualidad". RESULT: All final items have an item-total correlation over 0.29. A
      final questionnaire was obtained of 27 items, grouped into 6 components. The
      Cronbach's alpha coefficient indicated a high internal consistency of the test
      (0.881). Moreover, it confirms a significant difference between the sexes and
      between grades (cohorts). CONCLUSION: The Scale has appropriate parameters for
      use in sex education and research. The use of this scale would help to discover
      adherence to the myths of adolescents, in order to eliminate them and build a
      solid, free and personal concept of sexuality.

PMID- 30219645
TI  - [Pelvimetrics measures as predictives factors of positives surgical margins after
      robot-assisted laparoscopic prostatectomy].
AB  - INTRODUCTION: Anthropometric data report that pelvic bone of African subjects are
      narrower and the pelvic cavity is deeper. The aim of the study was to evaluate
      the influence of pelvic dimensions (PD) on Positive surgical margins (PSM) rate
      in Afro-Caribbean population after robot-assisted laparoscopic prostatectomy
      (RALP). PATIENTS AND METHODS: Preoperative pelvic MRI of all patients who have
      had RALP at the University Hospital Center of Guadeloupe between January 2013 and
      December 2015 was retrospectively analyzed. PD, including the Height of the upper
      edge of the prostate (HP), the Apical Depth (AD) and Ischial Spines Distance
      (ISD), and indexes (prostate volumetric index [ISD/VP], apical depth index
      [ISD/AD] and prostate depth index [ISD/(AD/HP)]) were compared according to the
      presence or absence of PSM with uni and multivariate analysis. RESULTS: One
      hundred and seventy-eight patients were included in the study, of whom 60 (33.7%)
      presented PSM. In univariate analysis, significant differences between the
      presence or absence of PSM were observed on the AD (30.3+/-8.7mm versus 24.8+/
      8.0mm, P<0.001), the HP (9.5+/-8.5mm versus 16.8+/-11.9mm, P<0.001) and the ISD
      (89.6+/-8.8mm versus 96.1+/-8.4mm) as well as the indexes of apical depth and
      prostatic depth. In multivariate logistic regression, the ISD (P<0.001) and HP
      (P=0.02) were associated with increased likelihood of PSM, but not AD or indexes.
      CONCLUSION: This study suggests that interspinous distance is the best predictor
      of PSM during RALP in Afro-Caribbean patients. This measure may be useful to
      define the therapeutic pattern of patients with prostate cancer. A prospective
      study with a larger population, comparing RALP in Afro-Caribbean and in
      caucasians patients, would be needed.

PMID- 30219646
TI  - [Prognostic value of PD-1/PD-L1 expression in upper tract urothelial carcinoma].
AB  - Current literature supports the efficacy of anti-PD-1 and anti-PD-L1 immune
      checkpoint inhibitors for the treatment of urothelial carcinomas. While the
      prognostic value of PD-1 and PD-L1 levels has been comprehensively analyzed for
      urothelial carcinoma of the bladder, less is known for upper tract urothelial
      carcinoma. In addition, available data on the prognostic value of PD-1 and/or PD
      L1 level in the tumor and/or peritumoral microenvironment are heterogeneous and
      even sometimes contradictory. In this article, we compared the methodologies of
      the various available studies in order to highlight the factors that can explain
      these discordant results.

PMID- 30219647
TI  - [Is transition from pure laparoscopic to robotic-assisted radical prostatectomy
      associated with increase of surgical procedures for urinary incontinence and
      erectile dysfunction?]
AB  - OBJECTIVE: To study the impact of changing the technique of radical prostatectomy
      [pure laparoscopic radical (PR-Lap) to robot-assisted radical prostatectomy (RP
      Rob)] on the rate of secondary procedures for urinary incontinence (UI) and
      erectile dysfunction (ED). MATERIAL: Retrospective study evaluating the number
      and type of surgical procedures for post-RP UI and DE between 2008 and 2015,
      according to the technique of (RP-Lap or RP-Rob). RESULTS: Between 2008 et 2015,
      2046 RP were performed in our department including 372 RP-Lap and 1674 RP-Rob.
      Among these patients, 84 (4%) had a surgical procedure for post-RP UI (18 AMS800,
      9 balloons Pro-Act, and 57 male slings) and 15 (0.7%) had implantation of penile
      prosthesis for post-RP ED; 16 (0.7%) patients had both procedures. The mean delay
      between RP and UI surgery decrease from 3.2 years in 2008 to 1 year in 2015 and
      remain stable for penile prosthesis implantation (mean delay: 3.4 years). The
      overall rates of secondary procedures for UI and DE remained stable and below 5%
      and 1.7%, respectively, even during the transition period. For each year of PR
      studied, the rates of secondary procedure were higher in the RP-Lap group.
      CONCLUSION: Changing the technique of RP from RP-Lap to PR-Rob has a favorable
      impact on the rate of secondary procedures for UI and ED from the outset.

PMID- 30219648
TI  - Normal-range albuminuria in healthy subjects increases over time in association
      with hypertension and metabolic outcomes.
AB  - Albuminuria is a prognostic factor for mortality and cardiovascular events, even
      at low levels. Changes in albumin excretion are associated with end-stage renal
      disease and hypertension (HTN) in cohorts including high-risk participants. We
      aimed to investigate the evolvement of albumin excretion in healthy individuals
      with normal kidney function and normoalbuminuria, and possible associations with
      HTN and metabolic outcomes. The study cohort consisted of 1967 healthy adults
      with normal kidney function (estimated glomerular filtration rate >= 90
      mL/min/1.73 m2; urine albumin to creatinine ratio [ACR] < 30 mg/g). Delta ACR
      slope was calculated as ACR difference between two consecutive visits divided by
      the time interval. During a mean follow-up period of 93.8 months, mean delta ACR
      slope was 0.27 +/- 3.29 mg/g/year and was higher in participants with age >40
      years, obesity, a high waist circumference, higher baseline ACR, HTN,
      prediabetes, and metabolic syndrome. Delta ACR slopes in the upper quartile
      predicted diabetes (OR = 1.31, P = .027) and albuminuria (4.34, P < .001). Upper
      quartile of ACR slopes correlated with a higher risk for new-onset HTN (1.249, P
      = .031). Delta systolic and diastolic blood pressures were associated with ACR
      slopes in addition to age, body mass index, and baseline ACR. In conclusion,
      accelerated change in ACR correlates with HTN and diabetes in healthy individuals
      with normal kidney function and normoalbuminuria.

PMID- 30219649
TI  - Clinical impact of dipping and nocturnal blood pressure patterns in newly
      diagnosed, never-treated patients with essential hypertension.
AB  - The significance of nondipping and increased nighttime systolic blood pressure
      (SBP) in established hypertension is well defined. We investigated whether these
      factors alone or combined correlate with vascular damage in early-stage
      hypertension. Newly diagnosed, untreated hypertensives were classified as dippers
      and nondippers according to ambulatory blood pressure (BP). Twenty-four-hour
      urinary albumin excretion and markers of arterial stiffness (pulse wave velocity,
      augmentation index, central and peripheral pulse pressure, central BP) and
      atherosclerosis (carotid intima-media thickness) were assessed. Serum asymmetric
      dimethylarginine, an index of endothelial dysfunction, was measured in a study
      subgroup; 10-year cardiovascular risk was calculated. Among 222 hypertensives,
      only urinary albumin excretion was increased in nondippers, compared to dippers
      (P = .026). When dippers were further stratified according to nighttime SBP (<120
      or >=120 mm Hg), the first group demonstrated the lowest levels of office,
      aortic, 24-hour, daytime and nighttime BP, compared to dippers with elevated
      nighttime SBP and nondippers. Although vascular measurements and asymmetric
      dimethylarginine were comparable between these groups, dippers with normal
      nighttime SBP exhibited the lowest cardiovascular risk score (P = .050). In early
      stage hypertension, nondipping was accompanied by microvascular, yet not
      macrovascular and endothelial dysfunction. Dippers with elevated nighttime SBP
      appear as a distinct group with increased hemodynamic pressure load and
      cardiovascular risk.

PMID- 30219651
TI  - Fibrillin protein pleiotropy: Acromelic dysplasias.
AB  - The fibrillins are large extracellular matrix molecules that polymerize to form
      microfibrils. Fibrillin microfibrils are distinctive architectural elements that
      are both ubiquitous in the connective tissue space and also unique, displaying
      tissue-specific patterns. Mutations in the genes for fibrillin-1 (FBN1) result in
      multiple distinct pleiotropic disorders. Most of the more than 3000 mutations
      known today in FBN1 cause the Marfan syndrome. Marfan mutations can occur in any
      of the 56 domains that compose fibrillin-1. In contrast, rare mutations in FBN1
      that are confined to only certain domains cause several different types of
      acromelic dysplasia. These genetic disorders demonstrate that specific domains of
      fibrillin-1 perform roles important to musculoskeletal growth. Many of the
      phenotypes of acromelic dysplasias are the opposite of those found in Marfan
      syndrome. Knowledge of the functions and structural organization of fibrillin
      molecules within microfibrils is required to understand how one protein and one
      gene can be the basis for multiple genetic disorders.

PMID- 30219650
TI  - Differing clinical features between Japanese and Caucasian patients with
      myelodysplastic syndromes: Analysis from the International Working Group for
      Prognosis of MDS.
AB  - Clinical features of myelodysplastic syndromes (MDS) could be influenced by many
      factors, such as disease intrinsic factors (e.g., morphologic, cytogenetic,
      molecular), extrinsic factors (e.g, management, environment), and ethnicity.
      Several previous studies have suggested such differences between Asian and
      European/USA countries. In this study, to elucidate potential differences in
      primary untreated MDS between Japanese (JPN) and Caucasians (CAUC), we analyzed
      the data from a large international database collected by the International
      Working Group for Prognosis of MDS (300 and 5838 patients, respectively). JPN MDS
      were significantly younger with more severe cytopenias, and cytogenetic
      differences: less del(5q) and more +1/+1q, -1/del(1p), der(1;7), -9/del(9q),
      del(16q), and del(20q). Although differences in time to acute myeloid leukemia
      transformation did not occur, a significantly better survival in JPN was
      demonstrated, even after the adjustment for age and FAB subtypes, especially in
      lower, but not in higher prognostic risk categories. Certain clinical factors
      (cytopenias, blast percentage, cytogenetic risk) had different impact on survival
      and time to transformation to leukemia between the two groups. Although possible
      confounding events (e.g., environment, diet, and access to care) could not be
      excluded, our results indicated the existence of clinically relevant ethnic
      differences regarding survival in MDS between JPN and CAUC patients. The good
      performance of the IPSS-R in both CAUC and JP patients underlines that its common
      risk model is adequate for CAUC and JP.

PMID- 30219652
TI  - Utilization of installation wound vacuum device for breast implant salvage:
      Approach and results.

PMID- 30219653
TI  - A simple method for lymphedema self-measurement using the Zozosuit bodysuit.

PMID- 30219654
TI  - From moon to earth-ultradian cycles in brain excitability.

PMID- 30219655
TI  - Circadian and circaseptan rhythms in human epilepsy: a retrospective cohort
      study.
AB  - BACKGROUND: Epilepsy has long been suspected to be governed by cyclic rhythms,
      with seizure rates rising and falling periodically over weeks, months, or even
      years. The very long scales of seizure patterns seem to defy natural explanation
      and have sometimes been attributed to hormonal cycles or environmental factors.
      This study aimed to quantify the strength and prevalence of seizure cycles at
      multiple temporal scales across a large cohort of people with epilepsy. METHODS:
      This retrospective cohort study used the two most comprehensive databases of
      human seizures (SeizureTracker [USA] and NeuroVista [Melbourne, VIC, Australia])
      and analytic techniques from circular statistics to analyse patients with
      epilepsy for the presence and frequency of multitemporal cycles of seizure
      activity. NeuroVista patients were selected on the basis of having intractable
      focal epilepsy; data from patients with at least 30 clinical seizures were used.
      SeizureTracker participants are self selected and data do not adhere to any
      specific criteria; we used patients with a minimum of 100 seizures. The presence
      of seizure cycles over multiple time scales was measured using the mean resultant
      length (R value). The Rayleigh test and Hodges-Ajne test were used to test for
      circular uniformity. Monte-Carlo simulations were used to confirm the results of
      the Rayleigh test for seizure phase. FINDINGS: We used data from 12 people from
      the NeuroVista study (data recorded from June 10, 2010, to Aug 22, 2012) and 1118
      patients from the SeizureTracker database (data recorded from Jan 1, 2007, to Oct
      19, 2015). At least 891 (80%) of 1118 patients in the SeizureTracker cohort and
      11 (92%) of 12 patients in the NeuroVista cohort showed circadian (24 h)
      modulation of their seizure rates. In the NeuroVista cohort, patient 8 had a
      significant cycle at precisely 1 week. Two others (patients 1 and 7) also had
      approximately 1-week cycles. Patients 1 and 4 had 2-week cycles. In the
      SeizureTracker cohort, between 77 (7%) and 233 (21%) of the 1118 patients showed
      strong circaseptan (weekly) rhythms, with a clear 7-day period. Between 151 (14%)
      and 247 (22%) patients had significant seizure cycles that were longer than 3
      weeks. Seizure cycles were equally prevalent in men and women, and peak seizure
      rates were evenly distributed across all days of the week. INTERPRETATION: Our
      results suggest that seizure cycles are robust, patient specific, and more
      widespread than previously understood. They align with the accepted consensus
      that most epilepsies have some diurnal influence. Variations in seizure rate have
      important clinical implications. Detection and tracking of seizure cycles on a
      patient-specific basis should be standard in epilepsy management practices.
      FUNDING: Australian National Health and Medical Research Council.

PMID- 30219656
TI  - Membrane protein structural biology in the era of single particle cryo-EM.
AB  - In the past few years, significant technological breakthroughs in single particle
      cryo-electron microscopy enabled a 'resolution revolution' of this technique. It
      also changed structural biology in an unprecedented way. For many biological
      macromolecules, obtaining well-ordered crystals of suitable size is no longer a
      prerequisite for determining their atomic structures. One of the most impacted
      areas is the structural biology of integral membrane proteins. New structures are
      now determined at a rapid pace. Despite these advances, further technological
      developments are still required to overcome new technical challenges that face
      membrane protein structural biology. In this review, I attempt to discuss some of
      these challenges.

PMID- 30219657
TI  - Added Value of Contrast-Enhanced T1-Weighted and Diffusion-Weighted Sequences for
      Characterization of Incidental Findings on Whole Body Magnetic Resonance Imaging
      in Plasma-Cell Disorders.
AB  - BACKGROUND: Whole body magnetic resonance imaging (WBMRI) is currently
      recommended by guidelines for the assessment of myeloma. This will inevitably
      result in incidental findings. We aimed to assess the frequency of extraskeletal
      incidental findings and the added value of contrast-enhanced (CE) T1-weighted (T1
      W) and diffusion-weighted (DWI) sequences for their characterization in a single
      WBMRI examination. PATIENTS AND METHODS: We performed 1.5 T WBMRI in 100 patients
      (53 female; median age, 65 years) with plasma-cell disorders from January 2014 to
      July 2017. T2-weighted sequences were reviewed initially for incidental findings,
      followed by sequential review of T1-W, CE T1-W, and DWI sequences for lesion
      characterization. Descriptive statistics were undertaken. RESULTS: A total of 348
      incidental findings were detected in 97 (97%) of 100 patients; only 38 (10.9%) of
      348 findings were indeterminate. T1-W sequences increased diagnostic confidence
      in the characterization of 12 (31.6%) of 38; CE T1-W sequences in the
      characterization of 16 (50%) of 32; and DWI increased diagnostic confidence in 21
      (55.3%) of 38 compared to the T2-weighted sequence alone. CONCLUSION: Incidental
      findings are common, but the majority are of no clinical consequence. No
      additional cancers were noted in our series. DWI and CE T1-W sequences increased
      diagnostic confidence in 50% of indeterminate findings and may reduce the need
      for further investigation.

PMID- 30219658
TI  - Anthracosilicosis mimicking extensive nodal metastasis from early gastric cancer:
      A case report.
AB  - INTRODUCTION: Lymph node metastasis is one of the most important prognostic
      factors in gastric cancer and precise assessment of nodal status facilitates
      optimal therapeutic decisions. Many diagnostic modalities including endoscopic
      ultrasound (EUS), computed tomography (CT), and sometimes, positron emission
      tomography (PET) have been utilized to improve diagnostic accuracy in detecting
      metastatic lymph nodes; however, their accuracy remains unsatisfactory.
      PRESENTATION OF CASE: We report a case of a 73-year old male patient who was
      erroneously diagnosed with stage IV gastric cancer due to the distant nodal
      metastasis from early gastric cancer lesion during the initial staging process.
      However, surgical exploration revealed an anthracosilicosis-associated
      lymphadenopathy that mimicked extensive distant nodal metastasis in the
      preoperative CT and PET-CT scans. The patient was finally diagnosed with stage I
      gastric cancer confined to the mucosa without nodal metastasis. DISCUSSION: We
      report a rare case of gastric cancer concurrent extensive nodal involvement of
      anthracosilicosis mimicking metastatic nodal disease in the imaging studies. This
      case implies that PET-CT scan for clinical staging is not specific enough to
      clearly delineate malignant lesions, causing a diagnostic dilemma. CONCLUSION:
      When the characteristics of the primary tumor is poorly correlated to the
      findings of imaging studies, surgical exploration can be a viable option for a
      definitive diagnosis before making a hasty decision based only upon the
      diagnostic imaging results.

PMID- 30219659
TI  - Coloseminal vesicle fistula after low anterior resection: Report of a case and
      review of the literature.
AB  - INTRODUCTION: A rectoseminal vesicle fistula after a low anterior resection for
      rectal cancer is a rare complication despite their anatomic proximity. From a
      Medline search from 1966 to date, a total of twenty-one previous cases of
      coloseminal vesicle fistula have been reported. From these cases, eleven were a
      complication of laparoscopic low anterior resection for rectal cancer.
      DESCRIPTION OF THE CASE: This report presents the case of a 63-year-old patient
      who was readmitted to the hospital on the fifteenth postoperative day after his
      surgical intervention for fever, abdominal pain, dysuria and pneumaturia. A
      sinography with water-soluble contrast revealed a tract between the rectum and
      the seminal vesicle. The condition was treated conservatively with antibiotics,
      urinary catheter and a transanastomotic Malecot probe for abscess drainage. The
      fistula had completely recovered on postoperative day 71 and the patient is still
      symptoms free, six months after the complication developed. DISCUSSION: This case
      reinforces the presumed link between anastomotic leakage and rectoseminal vesicle
      fistula in cases of low anterior resection while reviewing and summarizing
      similar previously reported cases on the course of the disease, diagnostic
      procedures and treatment options. CONCLUSION: Seminal vesicle are susceptible to
      fistula in oncological resection of rectum. Both CT scan with water-soluble
      contrast or sinography are effective diagnostic examinations. Depending on the
      characteristics of the fistula, conservative approach may be adequate and
      benefits much less morbidities than the surgical options.

PMID- 30219660
TI  - Differential diagnosis of solitary gastric Peutz-Jeghers-type polyp with stomach
      cancer: a case report.
AB  - INTRODUCTION: Solitary Peutz-Jeghers-type polyps of the stomach are extremely
      rare. They are defined as unique polyps that are not associated with Peutz
      Jeghers syndrome (PJS). PRESENTATION OF CASE: A 37-year-old woman presented at
      our hospital with anemia and epigastric discomfort. Esophagogastroduodenoscopy to
      determine the cause of anemia revealed a 5 * 6-cm pedunculated polypoid tumor at
      the greater curvature of the upper gastric body. Pathological examination of a
      biopsy specimen confirmed a Group 1 hyperplastic polyp. Computed tomography
      revealed neither lymph node swelling nor distant metastasis. A malignant
      component of the polypoid tumor was difficult to deny because of its size. The
      patient underwent local resection of the stomach. Her postoperative course was
      uneventful. A pathological examination of the surgical specimen revealed a Peutz
      Jeghers-type, hamartomatous polyp containing an enlarged crypt with hyperplastic
      foveolar epithelium and smooth muscle proliferating into the lamina propria. No
      atypical cells were found in the overlying epithelium. Based on these findings,
      we performed colonoscopy and capsule endoscopy of the intestine. No polyps were
      found in the intestine or colon. She had no family history of any type of tumor
      and no mucocutaneous pigmentation. DISCUSSION: There were only 10 reports of
      solitary gastric Peutz-Jeghers polyps published to date. Although most of them
      did not have atypical cells, one case has proliferative component. A few reports
      have described relationship with malignant tumor. CONCLUSION: Solitary gastric PJ
      type polyps are rare. Careful follow-up should be recommended and further studies
      are needed to evaluate cancer risk of solitary gastric PJ-type polyps.

PMID- 30219661
TI  - Preparation and characterization of nanostructured lipid carriers as drug
      delivery system: Influence of liquid lipid types on loading and cytotoxicity.
AB  - In this study, we aimed to investigate the influence of liquid lipid types on
      different features of NLC. Four variations of liquid lipids such as coconut oil,
      fish oil, black seed oil and linseed oil were used, while for all variations,
      cetyl palmitate was used as the solid lipid. Different NLC were characterized and
      compared in terms of particle size, zeta potential, polydispersity index (PDI),
      drug entrapment percentage and drug loading capacity. The results indicated that
      NLC containing black seed oil has the smallest size. Other features like PDI,
      zeta potential and entrapment efficiency were the same for all the liquid lipids.
      By close margins, the NLC containing black seed oil had the highest percent of
      drug release and antioxidant activity compared to the rest. Diffusion was the
      major mechanism of the drug release according to the drug release kinetic fitted
      by Higuchi's model. Differential scanning calorimetry (DSC) and fourier transform
      infrared spectroscopy (FT-IR) confirmed no strong interaction between NLC
      constituents. The particles showed spherical shape morphology under atomic force
      microscopy (AFM). According to the cell viability assay on MCF-7 cell line, the
      curcumin loaded NLC composed of linseed oil showed better cytotoxic activity
      compared to the free curcumin.

PMID- 30219662
TI  - Emergency of fungemia cases caused by fluconazole-resistant Candida auris in
      Beijing, China.
AB  - We describe the microbiological characterization and clinical presentation of two
      fungemia cases caused by fluconazole-resistant Candida auris in neonatal
      intensive care unit of a hospital in Beijing, China. We advocate for the need of
      guidelines or recommendations to improve identification, surveillance, and
      implementation of infection control measures in Chinese hospitals.

PMID- 30219664
TI  - Controversies in the Definition of Paraphilia.

PMID- 30219663
TI  - LipoxinA4 attenuates acute pancreatitis-associated acute lung injury by
      regulating AQP-5 and MMP-9 expression, anti-apoptosis and PKC/SSeCKS-mediated F
      actin activation.
AB  - An essential component of acute pancreatitis(AP)-induced acute lung injury(ALI)
      is the inflammation that is part of the body's systemic inflammatory response to
      a variety of systemic stimuli. Lipoxins(LXs) are considered important endogenous
      lipids that mediate the resolution of inflammation. In previous studies, we found
      that Lipoxin A4 (LXA4) reduced AP-induced pulmonary oedema and TNF-alpha
      production in lung. However, the underlying mechanism remains unclear. Due to the
      above studies, we investigated the aquaporin, matrix metalloprotein, apoptosis
      and PKC/SSeCKS signal pathway in cellular and animal models of AP-associated lung
      injury following LXA4 intervention. In this study, we first proved LXA4 could
      effectively promote F-actin reconstruction and regulate its expression in
      pulmonary microvascular endothelial cells both in vivo and vitro via suppressing
      PKC/SSeCKS signalling pathway. Next, we found that LXA4 attenuated cell growth
      inhibition and apoptosis in lung tissues of AP-ALI mice and HPMECs. Additionally,
      we demonstrated that LXA4 could regulate the expression of AQP-5 and MMP-9 to
      stabilize the permeability of pulmonary microvascular endothelial cell. In
      summary, our results suggest that the anti-inflammatory eff ;ects of LXA4 may be
      due to the inhibition of both the PKC/SSeCKS pathway and apoptosis to reduce
      alveolar fluid exudation and to the regulation of AQP-5 and MMP-9 expression to
      maintain the clearance of alveolar fluid. Thus, LXA4 is capable of exerting
      protective eff ;ects on AP-induced ALI.

PMID- 30219665
TI  - Bibliometric Analysis of Erectile Dysfunction Publications in Urology and Sexual
      Medicine Journals.
AB  - INTRODUCTION: Scientific literature has experienced a significant growth in the
      number of authors per publication each year. Erectile dysfunction (ED) is one of
      the most common urologic conditions, accounting for over 2.9 million outpatient
      visits per year. Given the prevalence of ED and the large literature base
      available on this condition, bibliometric analysis of the ED literature could
      provide urologists and sexual medicine specialists with a better understanding of
      publication trends in this topic area. AIM: The purpose of this study was to
      investigate trends in authorship, citations, and impact score for ED original and
      review articles published in urology and sexual medicine journals. METHODS: We
      analyzed ED original research and review articles indexed in MEDLINE between
      January 1, 2006, and December 31, 2016. Descriptive statistics were used to
      evaluate the mean number of authors for articles by journal type and time period
      (2006 vs 2016). Linear regression was used to examine the relationship between
      number of authors, number of citations, and relative citation ratio (RCR). MAIN
      OUTCOME MEASURE: The primary outcomes of interest included mean number of
      authors, citations, and RCR per manuscript by journal type and time period.
      RESULTS: A total of 3,516 articles were analyzed, 2,938 (83.6%) original and 578
      (16.4%) review articles. The mean number of authors among ED publications
      increased from 4.8 in 2006 to 6.4 in 2016, a 34.4% increase. Original articles
      had a greater mean number of authors compared to review articles (6.0 vs 4.3, P <
      .001). The mean number of authors for original articles significantly increased
      from 5.0 in 2006 to 7.0 in 2016 (P < .001), an increase of 38.9%. A positive
      linear relationship was observed between mean number of authors and number of
      citations per manuscript (r = 0.015, P < .01) as well as RCR (r = 0.37, P <
      .0001). The largest authorship increases were observed in European Urology
      (78.8%), BJU International (78.6%), and Journal of Sexual Medicine (58.1%).
      CLINICAL IMPLICATIONS: Authorship trends should be taken into consideration when
      urologists and sexual medicine experts review ED articles for the purpose of
      informing patient care. STRENGTH AND LIMITATIONS: Primary strengths include a
      large literature base spanning multiple years for analysis and a systematic
      literature search to identify relevant ED literature. Findings are limited to ED
      literature published in the urology and sexual medicine journals analyzed.
      CONCLUSION: The number of authors per ED manuscript has significantly increased
      over time, most notably among original research articles. Increasing authorship
      was associated with more citations and higher RCR in the ED literature. Rezaee
      ME, Johnson HA, Munarriz RM, et al. Bibliometric Analysis of Erectile Dysfunction
      Publications in Urology and Sexual Medicine Journals. J Sex Med 2018;15:1426
      1433.

PMID- 30219666
TI  - Sexual Quality of Life and Association With HIV and Sexually Transmitted
      Infections Among a Cohort of Heterosexual Couples in Kenya.
AB  - INTRODUCTION: Sexual quality of life (SQoL) is a critical component of sexual
      health and is understudied in Sub-Saharan African settings with endemic HIV and
      sexually transmitted infection (STI). AIM: We sought to assess SQoL among
      heterosexual couples in Kisumu, Kenya, and how this was associated with HIV
      status, STIs, and sexual practices. METHODS: This was a prospective cohort study
      of community-recruited couples. SQoL, HIV status, herpes simplex virus (HSV)-2
      status, bacterial vaginosis (BV), sexual practices, and sociodemographics were
      measured at baseline, 6 months, and 12 months. Multivariable linear regression
      with random intercept was fitted separately for females and males, accounting for
      partner characteristics. MAIN OUTCOME MEASURE: SQoL was assessed with an 18-item
      female and 11-item male survey. RESULTS: From April 2014 through July 2016, 252
      couples were enrolled, and followed up through September 2017. At baseline, women
      were median age 23 years, 10% HIV positive, 53% HSV-2 seropositive, and 22% with
      BV. At baseline men were median age 26 years, 12% HIV positive, 47% HSV-2
      seropositive, and 56% circumcised. Mean SQoL was higher for men (88) than women
      (78), with consistent scores over time. In multivariable analysis (P < .05 each),
      SQoL Questionnaire-Female (SQoL-F) score was reduced with: male partner report
      that sex felt rougher than he would have liked (9.5-point decrease), female HSV-2
      seropositivity (5.15-point decrease), female reported having dry vaginal sex
      (5.27-point decrease); among women with BV, SQoL-F score declined with recent
      sexual activity (8.27-point decrease) and increasing age (0.75-point decrease per
      1 year increase in age). Age and recent sex did not affect SQoL-F for women
      without BV. SQoL Questionnaire-Male score was decreased 4.99 points if male was
      employed, 4.52 points if male reported multiple recent sex partners, and 29.5
      points for HIV positive men whose female partner reported having sex when not in
      the mood. Men's SQoL increased by 0.84 points for each 1-U increase in female
      partner body mass index and 17.6 points for HIV positive men whose female partner
      reported recent sex with him. CLINICAL IMPLICATIONS: Within sexual partnerships,
      men had greater SQoL than women, and the adverse impact of BV and STIs on SQoL
      was greater for women than men. STRENGTH & LIMITATIONS: Research is needed to
      ensure relevant domains are measured in settings where measure of SQoL has not
      been validated, along with robust measures of physiologic and psychologic
      correlates. CONCLUSION: More attention to SQoL as an outcome may strengthen
      interventions aimed at preventing HIV and STIs and improving sexual health
      holistically. Mehta SD, Nordgren RK, Agingu W, et al. Sexual Quality of Life and
      Association With HIV and Sexually Transmitted Infections Among a Cohort of
      Heterosexual Couples in Kenya. J Sex Med 2018;15:1446-1455.

PMID- 30219667
TI  - Increase of follicular helper T cells skewed toward a Th1 profile in CVID
      patients with non-infectious clinical complications.
AB  - Common variable immunodeficiency (CVID) is characterized by low levels of
      circulating immunoglobulins and defects in B cell maturation leading to an
      increased susceptibility to infections. Some patients develop complications such
      as autoimmune diseases, enteropathy, and lymphoproliferation, resulting in higher
      morbidity and mortality. Follicular helper T (Tfh) cells are specialized in
      helping B cell differentiation into Ig-producing cells. Three subsets have been
      described, namely non B-cell helper Tfh1 and the two B-helper cell subsets Tfh2
      and Tfh17. We determined that circulating Tfh cells were elevated in CVID
      patients and skewed toward a Tfh1 profile. Interestingly, elevated levels of Tfh1
      cells were significant only in patients harboring non-infectious complications
      regardless of the type of complication and inversely correlated with switched
      memory B cells. Moreover, CXCR3+ cells are increased in splenic CVID germinal
      centers. Our observations suggest that the altered balance in Tfh subsets in CVID
      is linked to a more severe disease.

PMID- 30219668
TI  - State-dependent plasticity of innate behavior in fruit flies.
AB  - Behaviors are often categorized into innate or learned. Innate behaviors are
      thought to be genetically encoded and hardwired into the brain, while learned
      behavior is a product of the interaction between experience and the plasticity of
      synapses and neurons. Recent work in different models show that innate behavior,
      too, is plastic and depends on the current behavioral context and the internal
      state of an animal. Furthermore, these studies suggest that the neural circuits
      underpinning innate and learned behavior interact and even overlap. For instance,
      hunger modulates several innate behaviors relying in part on neural circuits
      required for learning and memory such as the mushroom body in the fruit fly.
      These new findings suggest that state-dependent innate behavior and learning rely
      on functionally and anatomically overlapping and shared neural circuits
      indicating a common evolutionary history.

PMID- 30219669
TI  - Pitfalls in the reporting of upper endoscopy features in cirrhotic patients.
AB  - BACKGROUND: Upper endoscopy is the main tool for the accurate assessment of the
      risk of bleeding in cirrhotic patients. AIM: To evaluate the diagnostic accuracy
      of upper endoscopy, in cirrhotic subjects, during common clinical practice.
      METHODS: 120 endoscopic reports produced in different hospitals in our region
      were retrospectively and randomly selected. After a general evaluation, aimed at
      assessing the description of various endoscopic features, reports were evaluated
      by four expert endoscopists and four expert hepatologists. Experts were asked to
      fill in a questionnaire for each single endoscopic procedure, regarding the
      diagnostic accuracy of the report. RESULTS: Endoscopic reports lacked
      descriptions of the size of esophageal varices and red signs in 14% and 29% of
      cases respectively. Presence (or absence) of gastric varices or portal
      hypertensive gastropathy were not reported in 62% and 34% of cases respectively.
      According to expert endoscopists 41% of the reports were incomplete, while,
      according to hepatologists, reports were incomplete and inadequate for clinical
      purposes in 36% of cases. CONCLUSION: Our study clearly evidenced a significant
      lack of information in reports on upper endoscopy in cirrhotic patients, and
      supports the prompt adoption of corrective strategies.

PMID- 30219671
TI  - Sirt3 attenuates post-infarction cardiac injury via inhibiting mitochondrial
      fission and normalization of AMPK-Drp1 pathways.
AB  - Mitochondrial damage is involved in the pathogenesis of post-infarction cardiac
      injury. However, the upstream regulators of mitochondrial damage have not yet
      been identified. The aim of our study is to explore the role of Sirt3 in post
      infarction cardiac injury with a particular focus on mitochondrial fission and
      AMPK-Drp1 pathways. Our results indicated that Sirt3 was downregulated in the
      progression of post-infarction cardiac injury. Overexpression of Sirt3 attenuated
      cardiac fibrosis, sustained myocardial function, inhibited the inflammatory
      response, and reduced cardiomyocyte death. Functional studies illustrated that
      chronic post-infarction cardiac injury was characterized by increased
      mitochondrial fission, which triggered mitochondrial oxidative stress, metabolic
      disorders, mitochondrial potential reduction and caspase-9 apoptosis in
      cardiomyocytes. However, Sirt3 overexpression attenuated mitochondrial fission
      and thus preserved mitochondrial homeostasis and cardiomyocyte viability.
      Furthermore, our results confirmed that Sirt3 repressed mitochondrial fission via
      normalizing AMPK-Drp1 pathways. Inhibition of AMPK activity re-activated Drp1 and
      thus abrogated the inhibitory effect of Sirt3 on mitochondrial fission.
      Altogether, our results indicate that Sirt3 enhancement could be an effective
      approach to retard the development of post-infarction cardiac injury via
      disrupting mitochondrial fission and normalizing the AMPK-Drp1 axis.

PMID- 30219670
TI  - Pancreatic cancer: French clinical practice guidelines for diagnosis, treatment
      and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, AFC).
AB  - BACKGROUND: This document is a summary of the French intergroup guidelines
      regarding the management of pancreatic adenocarcinoma (PA), updated in July 2018.
      DESIGN: This collaborative work was produced under the auspices of all French
      medical and surgical societies involved in the management of PA. It is based on
      the previous guidelines, recent literature review and expert opinions.
      Recommendations were graded in three categories, according to the level of
      evidence. RESULTS: Over the last seven years, significant changes in PA
      management have been implemented in clinical practice. Imaging/staging: diffusion
      magnetic resonance imaging is useful before surgery to rule out small liver
      metastases. SURGERY: centralization of pancreatic surgery in expert centers is
      associated with a decreased postoperative mortality. Adjuvant chemotherapy:
      modified FOLFIRINOX in fit patients, or gemcitabine, or 5-FU, or gemcitabine plus
      capecitabine, to be discussed on a case-by-case basis. Locally advanced PA: no
      survival benefit of chemoradiotherapy. Metastatic PA: FOLFIRINOX and gemcitabine
      plus nab-paclitaxel combination are first-line standards in fit patients; second
      line with 5FU/nal-IRI or 5FU/oxaliplatin combination after first-line
      gemcitabine. CONCLUSION: Guidelines for management of PA are continuously
      evolving and need to be regularly updated. This constant progress is made
      possible through clinical and translational research. However, as each individual
      case is particular, they cannot substitute to multidisciplinary tumor board
      discussion.

PMID- 30219672
TI  - An electrochemical biosensor to distinguish between normal and cancer cells based
      on monitoring their acidosis using gold-coated silicon Nano-roughened electrode.
AB  - One of the most interesting fields of research in cancer diagnosis is tracing the
      relation between extracellular media and cancer progression. Detecting the
      secreting contents of the cells and translating these molecular identifications
      into label-free recognizable patterns would open new opportunities in cancer
      research. Electrochemical responses are in the range of most attractive sensing
      mechanisms especially in biochemical approaches. Perturbed ionic exchanges as a
      known biochemical function of cancer cells presented a strong correlation with
      the pH of the tumor microenvironment. Different ionic activities detected by an
      electrochemical bio-sensing system in the malignant and normal cells in the
      presence of acidic ambient were our main results presented in this research.
      Herein, silicon Nano-roughened substrate as a well-known electrochemical
      interface was applied in the construction of the biosensor. Viability rate as
      well as apoptotic factors involving in cancer progression were assessed by
      biochemical assays in normal (MCF10A) and cancer (MCF7 and MDA-MB468) breast
      cells. Our findings demonstrated that pH-based electrochemical responses were
      matched with the results obtained from the biological analyses of both normal and
      malignant cells. Induction of acidosis in the cells followed by monitoring their
      electrochemical responses would be a new trend in microenvironment based cancer
      investigation.

PMID- 30219673
TI  - Novel circular RNA, hsa_circ_0025039 promotes cell growth, invasion and glucose
      metabolism in malignant melanoma via the miR-198/CDK4 axis.
AB  - Malignant melanoma, a tumor derived from melanocytes, shows severe drug
      resistance and prompt metastasis, causing a serious threat to human health.
      Circular RNAs (circRNAs) are widely expressed in mammals and have been indicated
      to play important roles in tumorigenesis. In the present study, we analyzed the
      variability of circRNAs in malignant melanoma by microarray and identified six
      differentially expressed circRNAs. In particular, we found that hsa_circ_0025039,
      which is formed by FOXM1 exons, is significantly upregulated in melanoma. In
      vitro, the knockdown of circ_0025039 inhibited cell proliferation, colony
      formation ability, invasion and glucose metabolism in melanoma cells.
      Additionally, we identified miR-198 as a direct target of hsa_circ_0025039.
      Furthermore, we demonstrated that hsa_circ_0025039 regulates CDK4 expression by
      sponging miR-198. In vivo study indicated that the silencing of hsa_circ_0025039
      inhibits melanoma tumor formation and downregulates miR-198 and CDK4 expression.
      Taken together, our data showed that circ_0025039 promotes cell growth, invasion
      and glucose metabolism in malignant melanoma by sponging miR-198 and regulating
      CDK4.

PMID- 30219674
TI  - Imbalance between T helper 17 and regulatory T cell subsets plays a significant
      role in the pathogenesis of systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a rare autoimmune disease that is characterized by
      fibrosis, inflammation, and vasculopathy of the skin and internal organs. The
      etiopathogenesis of SSc remains unclear. However, the pivotal role of T
      lymphocytes with an aberrant immune response in SSc is well established. Among T
      cells, IL-17-producing helper T (Th17) cell and regulatory T (Treg) cell subsets
      have recently been found to play crucial roles in SSc pathogenesis. Generally
      speaking, Th17 cell subsets up-regulate inflammation, fibrosis, and autoimmunity,
      which are present in SSc, while Treg cell subsets have an immunosuppressive
      function and resist the immunological performance of Th17 cells. Up-to-date
      evidence has pointed out that the imbalance and abnormal functions of Th17/Treg
      cells may contribute to SSc. Therefore, this review aims to summarize the current
      understanding of the vital cytokines and signaling pathways that are involved in
      Th17/Treg differentiation and functions, and their roles in the pathogenesis of
      SSc, thus providing novel insights about targeting the Th17/Treg balance as a
      potential therapy for SSc treatment in the near future.

PMID- 30219675
TI  - The influence of gut microbiota dysbiosis to the efficacy of 5-Fluorouracil
      treatment on colorectal cancer.
AB  - Colorectal cancer is one of the most frequently diagnosed cancers worldwide. Gut
      flora can modulate the host response to chemotherapeutic drugs. However, the
      understanding regarding the relationship between the gut microbiota and the
      antitumor efficacy of 5- Fluorouracil (5-FU) treatment is limited. Therefore, we
      compared the tumor size and profiled the gut microbiota of mice treated with 5
      FU, combined with probiotics or ABX (an antibiotic cocktail of antibiotics) by
      using the Colorectal Cancer (CRC) mouse model and high-throughput sequencing. The
      results elucidated that ABX administration diminished the antitumor efficacy of 5
      FU in mice and supplementation of probiotics upon 5-FU treatment could not
      significantly increase the efficacy of 5-FU treatment, despite improving mice
      body weight at day 33. There were significant differences in fecal bacteria
      community among the four groups (ANOSIM p < 0.05). ABX administration reduced
      microbiota biodiversity and altered microbiota community. The pathogenic bacteria
      included Escherichia shigella and Enterobacter significantly increased, while
      other commensal bacterial decreased unidentified Firmicutes increased and the
      opportunistic pathogens decreased after the administration of Probiotics. In
      addition, 5-FU treatment also changed the diversity and the community composition
      of the gut mirobiota. The relative abundance of genus Lachnospiracea_NK4 A136,
      Bacteroides, Odoribacter, Mucispirillum, and Blautia were significantly increased
      compared to the control group. Additionally, functional capacity analysis of gut
      microbiota using PICRUSt showed that genes involved in amino acid metabolism,
      replication and repair translation, nucleotide metabolism expressed much lower in
      FU.ABX group than the other groups. The current results suggest that ABX
      administration disrupted the gut microbiota in mice, which contributed to the
      reduction of antitumor efficacy of 5-FU.

PMID- 30219676
TI  - PTBP1 knockdown overcomes the resistance to vincristine and oxaliplatin in drug
      resistant colon cancer cells through regulation of glycolysis.
AB  - Drug-resistant cancer cells exhibit increased glycolysis, and targeting
      glycolysis is considered as a novel strategy to overcome drug resistance.
      Polypyrimidine tract-binding protein (PTBP1) has been found to be a regulator of
      glycolysis, however, the role of PTBP1 in drug resistance remains to be
      elucidated. Herein, we found that PTBP1 was highly expressed in two drug
      resistant colon cancer cell lines, vincristine-resistant HCT-8 cell line (HCT
      8/V) and oxaliplatin-resistant HCT116 cell line (HCT116/L-OHP). The levels of
      glucose consumption and lactate production as well as expression of pyruvate
      kinase M2 isoform (PKM2) and hexokinase II (HK2) were elevated, while PKM1 level
      was reduced in HCT-8/V and HCT116/L-OHP cells when compared with the HCT-8 and
      HCT116 cells. PTBP1 knockdown enhanced the sensitivity of HCT-8/V and HCT116/L
      OHP cells to vincristine and oxaliplatin, and caused reduction in glucose
      consumption and lactate production. PKM2 expression, but not HK2, was decreased
      and PKM1 expression level was increased in cells transfected with si-PTBP1. In
      addition, PTBP1 overexpression significantly induced glycolysis and reduced drug
      sensitivity, whereas the effects were attenuated by si-PKM2. Treatment with 2
      deoxyglucose (2-DG) also attenuated the effect of PTBP1 overexpression on drug
      sensitivity. In conclusion, PTBP1 knockdown enhanced the sensitivity of drug
      resistant colon cancer cells to vincristine and oxaliplatin through repression of
      glycolysis. Our study provided a promising therapeutic strategy to overcome drug
      resistance in colon cancer cells.

PMID- 30219677
TI  - Xin-Jia-Xiang-Ru-Yin alleviated H1N1-induced acute lung injury and inhibited the
      IFN-gamma-related regulatory pathway in summer flu.
AB  - Seasonal influenza is an acute viral infection caused by influenza virus, which
      is often prevalent in summer and winter. In contrast to the prevalent focus on
      winter flu, summer flu is often ignored by epidemiological researchers. However,
      summer flu should be studied because of the special immune status and the
      influenza spread mechanism in the hot and humid environment. Moreover, people are
      more likely to catch a summertime cold upon suddenly entering relatively cool air
      conditioning from the hot and humid environment. To simulate summer flu, we
      established a flu animal model under a high temperature and humidity environment
      during the day with a relatively low temperature at night to investigate the anti
      influenza virus effect and mechanism of Xin-Jia-Xiang-Ru-Yin. The results of RT
      qPCR verified virus replication, while pathological sections showed inflammation.
      The expression of the IFN-gamma-related regulatory pathway was measured by PCR
      and immunohistochemistry. We concluded that Xin-Jia-Xiang-Ru-Yin, which combined
      antiviral therapy and immune modulation effects, might have important therapeutic
      benefits against summer flu.

PMID- 30219678
TI  - Metabolism of liver CYP450 and ultrastructural changes after long-term
      administration of aspirin and ibuprofen.
AB  - Worldwide, aspirin and ibuprofen are the most commonly used non-steroidal anti
      inflammatory drugs (NSAIDs). Some adverse reactions, including gastrointestinal
      reactions, have been concerned extensively. Nevertheless, the mechanism of liver
      injury remains unclear. In the present study, we focused on the metabolism of
      liver cytochrome P450 (CYP450) and ultrastructural morphology of liver cells. A
      total of thirty rats were divided into three groups of 10. Rats in the aspirin
      and ibuprofen groups were given enteric-coated aspirin (15 mg/kg) and ibuprofen
      (15 mg/kg), respectively by gavage for four weeks. The body weights were recorded
      every two days. Liver function and metabolic capacity of CYP450 were studied on
      days 14 and 28. We then conducted ultrastructural examinations. Body weights in
      the Ibuprofen group were lower than those of the Control group, and ALT and AST
      levels were significantly higher (P < 0.05). There were no significant
      differences in terms of body weight, ALT or AST between the Aspirin and Control
      groups. The metabolic capacity of CYP450 was evaluated using five probe drugs,
      phenacetin, tolbutamide, metoprolol, midazolam, and bupropion. We found that
      ibuprofen and aspirin induced metabolism of the probe drugs. Moreover, according
      to the pharmacokinetic data, the Control, Aspirin and Ibuprofen groups could be
      discriminated accurately. Ultrastructural examination showed that the number of
      mitochondria was increased in both the Ibuprofen and Aspirin groups. Long-term
      administration of enteric-coated aspirin and ibuprofen induced the metabolic
      activity of the CYP450 enzyme. Aspirin had better tolerability than did
      ibuprofen, as reflected by pharmacokinetic data of probe drug metabolism.

PMID- 30219679
TI  - Culture filtrate ether extracted metabolites from Streptomyces levis ABRIINW111
      increased apoptosis and reduced proliferation in acute lymphoblastic leukemia.
AB  - Despite the advances in the discovery of various types of anticancer drugs for
      curing acute lymphoblastic leukemia (ALL), their toxicity and unfavorable side
      effects remained as big limitations for therapeutical applications. In this
      regard, natural products such as Streptomyces -derived agents have shown
      potential applications as anticancer drugs. The present study deals with
      evaluating the anti-carcinogenic activity of the ether extracted metabolites
      derived from Streptomyces on nalm-6 and molt-4 ALL cell lines. MTT assay was
      performed to evaluate the cytotoxicity effect of Streptomyces sp on nalm-6 and
      molt-4 cell lines. Apoptosis and proliferation were evaluated by Flow cytometry.
      Quantitative real-time RT-PCR (qRT-PCR) and western blot were performed to
      investigate the effect of these metabolites on the mRNA and protein expression
      levels of P53, Bax, and Bcl2. In both cell lines, extracted metabolites
      significantly inhibited cell growth and increased apoptosis. Although P53, Bax
      mRNA and protein expressions were increased, Bcl-2 expression decreased in
      treated cells compared with control. In addition, the G0/G1 arrest of Nalm-6
      cells was induced. These findings of this work show that the ether-extracted
      metabolites from Streptomyces levis ABRIINW111 can be used as an anti
      carcinogenic for acute lymphoblastic leukemia cells.

PMID- 30219680
TI  - Sinapic acid ameliorates bleomycin-induced lung fibrosis in rats.
AB  - BACKGROUND: Pulmonary fibrosis is a multifaceted disease with high mortality and
      morbidity, and it is commonly nonresponsive to conventional therapy. PURPOSE: We
      explore the possible discourse of sinapic acid (SA) against the prevention of
      bleomycin (BLM)-instigated lung fibrosis in rats through modulation of Nrf2/HO-1
      and NF-kappaB signaling pathways. DESIGN/METHODS: Lung fibrosis was persuaded in
      Sprague-Dawley rats by a single intratracheal BLM (6.5 U/kg) injection. Then,
      these rats were treated with SA (10 and 20 mg/kg, p.o.) for 28 days. The normal
      control rats provided saline as a substitute of BLM. The lung function and
      biochemical, histopathological, and molecular alterations were studied in serum,
      bronchoalveolar lavage fluid (BALF), and the lungs tissues. RESULTS: SA treatment
      significantly restored BLM-induced alterations in body weight index and serum
      biomarkers [lactate dehydrogenase (LDH) and alkaline phosphatase (ALP)]. SA (10
      and 20 mg/kg) treatment appeared to show a pneumoprotective effect through
      upregulation of antioxidant status, downregulation of inflammatory cytokines and
      MMP-7 expression, and reduction of collagen accumulation (hydroxyproline). Nrf2,
      HO-1, and TGF-beta expression was downregulated in BLM-induced fibrosis model,
      while the reduced expression levels were significantly and dose-dependently
      upregulated by SA (10 and 20 mg/kg) treatment. We demonstrated that SA
      ameliorates BLM-induced lung injuries through inhibition of apoptosis and
      induction of Nrf2/HO-1-mediated antioxidant enzymes via NF-kappaB inhibition. The
      histopathological findings also revealed that SA treatment (10 and 20 mg/kg)
      significantly ameliorated BLM-induced lung injury. CONCLUSION: The present
      results showed the ability of SA to restore the antioxidant system and to inhibit
      oxidative stress, proinflammatory cytokines, extracellular matrix, and TGF-beta.
      This is first report demonstrating that SA amoleriates BLM induced lung injuries
      through inhibition of apoptosis and induction of Nrf2 and HO-1 mediated
      antioxidant enzyme via NF-kappaB inhibition. The histopathological finding
      reveals that SA treatment (10 and 20 mg/kg) significantly ameliorates BLM induced
      lung injuries.

PMID- 30219681
TI  - Effects of silymarin on angiogenesis and oxidative stress in streptozotocin
      induced diabetes in mice.
AB  - The present study evaluated the effects of acute treatment with silymarin, an
      extract that is obtained from Silybum marianum, on angiogenesis, oxidative
      stress, and inflammation in normoglycemic and diabetic mice. Diabetes was induced
      by streptozotocin (80 mg/kg, intraperitoneal) in male Swiss mice, 6 weeks of age.
      A polyether-polyurethane sponge was surgically implanted in the back of the mice
      as a model of healing in both diabetic and normoglycemic animals that were
      treated with oral silymarin or water for 10 days. The pancreas, liver, kidneys,
      blood, and sponges were collected and analyzed. Diabetes led to impairments of
      antioxidant defenses, reflected by a reduction of pancreatic superoxide dismutase
      and hepatic and renal catalase and an increase in pancreatic lipoperoxidation. An
      inflammatory process was observed in diabetic mice, reflected by an increase in
      pancreatic tumor necrosis factor alpha (TNF-alpha) and the infiltration of
      inflammatory cells in islets. The number of vessels was lower in the implanted
      sponges in diabetic mice. Silymarin treatment attenuated this damage, restoring
      antioxidant enzymes and reducing pancreatic TNF-alpha and inflammatory
      infiltration. However, silymarin treatment did not restore angiogenesis or
      glycemia. In conclusion, treatment with silymarin red uced oxidative stress and
      inflammation that were induced in the model of streptozotocin-induced diabetes in
      several organs, without apparent toxicity. Silymarin may be a promising drug for
      controlling diabetic complications.

PMID- 30219682
TI  - Lipocalin-2 protects against renal ischemia/reperfusion injury in mice through
      autophagy activation mediated by HIF1alpha and NF-kappab crosstalk.
AB  - Renal ischemia/reperfusion injury is a main cause of acute kidney injury (AKI)
      triggering an inflammatory response associated with infiltrating macrophages.
      Lipocalin-2 (Lcn2) levels correlate positively and protect against renal
      ischemia/reperfusion injury. However, the mechanisms remain unclear. The aim of
      study was to investigate the protective mechanisms of Lcn2 on renal
      ischemia/reperfusion injury. We found that Lcn2 deficiency significantly
      aggravated renal injury as evidenced by higher serum creatinine, more severe
      morphological injury, and increased tubular epithelial cell death in mice. We
      also observed that attenuated autophagy in Lcn2-/- mice, as autophagy markers LC3
      II level was significantly decreased and p62 was increased in the Lcn2-/- mice
      after I/R, compared with that of wild type. Mechanistically, we found that
      recombinant Lcn2 attenuated hypoxia-induced apoptosis in proximal tubule
      epithelial cells in vitro, and downregulation of HIF-1alpha blunted Lcn2-induced
      autophagy and enhanced apoptosis. In addition, the Lcn2 attenuated NF-kappab
      subunit p65 activation under hypoxia conditions. Thus, our findings provide a
      better understanding of the protective role of Lcn2 in kidney
      ischemia/reperfusion injury and suggest that Lcn2 may be a promising therapeutic
      target for treating patients with AKI.

PMID- 30219683
TI  - Association of HTR2A-1438G/A Genetic Polymorphism With Smoking and Chronic
      Obstructive Pulmonary Disease.
AB  - INTRODUCTION: Cigarette smoking is a major risk factor in the development of
      chronic obstructive pulmonary disease (COPD). Serotonin levels have been
      associated with COPD and smoking has been as a significant modulator. Elevated
      levels of serotonin are responsible for bronchoconstriction and pulmonary
      vasoconstriction and also nicotine dependence, thus serotonin response could be
      affected by genetic polymorphisms in transporters and receptors of serotonin.
      OBJECTIVES: The aim of the current study was to analyze the effect of SLC6A4
      (5HTT_LPR) (rs25531) and HTR2A-1438G/A (rs6311) genetic polymorphisms on the
      relation between smoking habits and COPD. METHODS: The association between SLC6A4
      (5HTT_LPR) (rs25531), HTR2A-1438G/A (rs6311), smoking degree and COPD was
      analyzed in a total of 77 COPD patients (active smokers) and 90 control subjects
      (active healthy smokers). The DNA was extracted of peripheral leukocytes samples
      and genotyping was performed using an allele specific polymerase chain reaction.
      RESULTS: The distribution of SLC6A4 genotypes did not vary between healthy
      smokers and COPD patients (P=0.758). On the other hand, the A allele of HTR2A
      (rs6311) was significantly associated with COPD incidence in the trend model
      (P=0.02; 1.80 [1.04-3.11]). Among all smokers, this allele was also associated
      with the number of pack years smoked (P=0.02) and also, we observed a marginal
      association with FEV1/FVC values (P=0.06). CONCLUSION: Our results point a
      possible role of the A allele of HTR2A (rs6311) in COPD pathogenesis, suggesting
      that this effect depends partly on tobacco consumption due to a gene-by
      environment interaction.

PMID- 30219684
TI  - Nutrition support team activities can improve enteral nutrition administration in
      intensive care units.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of the nutritional
      support team (NST) activities on the quality of enteral nutrition administration
      in intensive care units. METHODS: An observational, analytical, and cross
      sectional study was performed in nine hospitals in the Brazilian Federal District
      through the administration of two questionnaires. One questionnaire focused on
      the activities of the NST and the other on the quality of enteral nutrition
      administration in intensive care units. RESULTS: There was a strong correlation
      between the scores of the two questionnaires, which was confirmed by a linear
      regression model (R2 = 0.623; P = 0.007). The results suggest that high scores in
      the NST activities questionnaire predict a better performance in enteral
      nutrition administration. The sections of the NST activity questionnaire that
      most strongly affected enteral nutrition administration were the protocols (r =
      0.895; P < 0.01), quality control (r = 0.779; P < 0.05), and continuing education
      (r = 0.753; P < 0.05). CONCLUSIONS: The NST has the potential to positively
      influence enteral nutrition management in intensive care units and investments
      could be directed to the areas of continuing education, protocols, and quality
      control to maximize the effect of NST in intensive care units.

PMID- 30219685
TI  - Obstructive sleep apnea in non-dialyzed chronic kidney disease patients:
      Association with body adiposity and sarcopenia.
AB  - OBJECTIVES: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular
      disease (CVD), the main cause of mortality in chronic kidney disease (CKD).
      Although the prevalence of OSA in patients with CKD has not been established, a
      few studies suggest that it is higher than in the general population, potentially
      increasing the risk for CVD. Obesity increases the risk, whereas sarcopenia has
      been suggested as a consequence of OSA in the general population. To our
      knowledge, these associations have not been adequately evaluated in patients with
      CKD. The aim of this study was to evaluate OSA frequency and its association with
      total and upper body adiposity and sarcopenia in non-dialyzed CKD patients.
      METHODS: This cross-sectional study included 73 patients with stages 3b-4 CKD (42
      men, 62.9 +/- 1.1 y of age). Glomerular filtration rate was estimated by the CKD
      Epidemiology Collaboration equation. Patients were assessed for OSA by Watch
      PAT200 (apnea-hypopnea index >=5 events hourly; Itamar Medical), total body
      adiposity by dual-energy x-ray absorptiometry (DXA) and body mass index (BMI),
      upper body adiposity by anthropometric parameters and by trunk and visceral fat
      by DXA, and sarcopenia. RESULTS: OSA frequency was 67% (N = 49). Both total and
      upper body adiposity were associated with the presence and severity of OSA. In
      non-obese patients (BMI <30 kg/m2), upper body obesity increased significantly
      the frequency of OSA. OSA association with sarcopenia was blunted when BMI was
      included in regression model. CONCLUSIONS: Results from the present study suggest
      that in non-dialyzed CKD patients OSA is very common and associated with total
      and upper body obesity, but not with sarcopenia.

PMID- 30219686
TI  - Weight loss and metabolic improvements in obese patients undergoing gastric
      banding and gastric banded plication: A comparison.
AB  - OBJECTIVES: Obesity is a pandemic health problem. Bariatric surgery is the only
      efficient method for long-term effective weight loss in subjects with severe
      obesity. Laparoscopic adjustable gastric banding (LAGB) has been widely applied
      for weight loss. However, a novel technique called laparoscopic adjustable
      gastric banded plication (LAGBP) has been proposed as an alternative to LAGB.
      Surgeons generally consider LAGBP to have a relative advantage on weight loss
      than that derived from LAGB. This initial study applied various biostatistical
      models and considered a relative longer observation period to compare the effects
      of LAGB and LAGBP. METHODS: A total of 340 obese patients (290 who underwent LAGB
      and 50 who underwent LAGBP) with a body mass index of >=35 kg/m2 and ages 20 to
      55 y were recruited from the Division of General Surgery, Taipei Medical
      University Hospital in Taipei, Taiwan and observed for 24 to 36 mo
      postoperatively. RESULTS: Both surgical procedures resulted in significant weight
      loss, amelioration of poor glucose metabolism, and decreased serum
      triacylglycerol levels. However, the trend analysis showed no significant
      differences between the postoperative effects of LAGB and LAGBP (P for trend =
      0.21 for body mass index reduction, 0.13 for total body fat percentage reduction,
      0.25-0.29 for glucose metabolism amelioration, and 0.10-0.29 for blood pressure
      improvement). Improvements in serum total cholesterol and high-density
      lipoprotein cholesterol levels were observed after LAGB only and LAGBP only,
      respectively, at 24 mo postoperatively. The Framingham Coronary Heart Disease
      Risk score also showed significant decrease for patients who underwent LAGB and
      LAGBP. CONCLUSIONS: Both LAGB and LAGBP demonstrated comparable efficacy in
      reducing body weight and improving metabolic parameters in a 24 to 36 mo follow
      up period. LABG showed the ability to reduce systolic blood pressure and LAGBP
      exhibited triacylglycerol-lowering effects. A longer observational period is
      needed in future studies.

PMID- 30219687
TI  - Psychological distress and completed suicide in Japan: A comparison of the impact
      of moderate and severe psychological distress.
AB  - It has already been established that severe psychological distress is a major
      risk factor for completed suicide. However, the impact (population attributable
      fraction; PAF) of moderate psychological distress on completed suicide has not
      been clarified. The present study investigated the association between various
      severities of psychological distress and completed suicide. We analyzed follow-up
      data covering a 7.3-year period (2006-2014) for 43,473 adults (aged >= 40 years)
      participating in a community-based, prospective cohort study. Psychological
      distress was measured using the K6 psychological distress scale at the baseline.
      Participants were classified into three groups according to their K6 score (low:
      0-4; moderate: 5-12; severe: 13-24). Completed suicide was determined from a
      Japanese national database. The Cox model was used to estimate hazard ratios
      (HRs) for completed suicide. The PAFs of moderate and severe psychological
      distress for completed suicide were also estimated. The multivariate-adjusted HRs
      (95% confidence interval) for completed suicide were 2.37 (1.49-3.78) among
      participants with moderate psychological distress, and 4.16 (2.13-8.15) among
      those with severe psychological distress, relative to those with low
      psychological distress (P for trend < 0.001). The PAF of the moderate group for
      completed suicide was 26.8%, whereas that of the severe group was 10.9%. Not only
      severe but also moderate psychological distress was significantly associated with
      an increased risk of completed suicide. The PAF of moderate psychological
      distress for completed suicide was larger than that of severe psychological
      distress. Public health actions for suicide prevention should focus on moderate
      as well as severe psychological distress.

PMID- 30219688
TI  - Sex-specific relationship between visceral fat index and dyslipidemia in Chinese
      rural adults: The Henan Rural Cohort Study.
AB  - The study aimed to explore the relationship between visceral fat index (VFI) and
      dyslipidemia and evaluate the efficiency of VFI as a marker for identifying
      dyslipidemia in Chinese rural adults. The cross-sectional study recruited 35,832
      aged 18-79 years eligible participants from The Henan Rural Cohort Study. VFI was
      measured by bioelectrical impendence methods and classified into sex-specific
      quartiles. Fasting blood samples were collected. Logistic regression models with
      VFI as a categorical variable and restricted cubic spline regression models with
      VFI as a continuous variable were performed to obtain odds ratios (ORs) and 95%
      confidence intervals (CIs). Receiver-operating characteristic (ROC) curve was
      conducted to evaluate the identifying performance of VFI. The age-standardized
      prevalence of dyslipidemia was 29.80% and 26.01% in male and female,
      respectively. Increasing VFI quartiles were significantly positively related to
      the risk of dyslipidemia and its components (Pfor trend < 0.01). The adjusted ORs
      (95% CIs) for per 1-SD increase in VFI were 2.11 (2.02-2.20) and 1.52 (1.47-1.56)
      in male and female, respectively, and dose-response relationships were observed
      in both genders (Pfor nonlinearity < 0.01). In addition, area under the curves
      (AUCs) in male (0.697) was larger than in female (0.655) (P < 0.05). VFI was
      significantly positively related to the risk of dyslipidemia and its components,
      and the risk was shown to be more prominent in male. Meanwhile, dose-response
      relationships were observed in both genders. Furthermore, VFI might be a
      relatively effective marker for identifying dyslipidemia in male, but not in
      female.

PMID- 30219689
TI  - Florida physicians' reported use of AFIX-based strategies for human
      papillomavirus vaccination.
AB  - HPV vaccination rates in Florida are low. To increase rates, the CDC recommends
      clinics adhere to components of their evidence-based quality improvement program,
      AFIX (Assessment, Feedback, Incentives, and eXchange of information). We explored
      factors associated with engaging in HPV-specific AFIX-related activities. In
      2016, we conducted a cross-sectional survey of a representative sample of 770
      pediatric and family medicine physicians in Florida and assessed vaccination
      practices, clinic characteristics, and HPV-related knowledge. Data were analyzed
      in 2017. The primary outcome was whether physicians' clinics engaged in >=1 AFIX
      activity. We stratified by physician specialty and developed multivariable models
      using a backward selection approach. Of the participants in the analytic sample
      (n = 340), 52% were male, 60% were White of any ethnicity, and 55% were non
      Hispanic. Pediatricians and family medicine physicians differed on: years
      practicing medicine (p < 0.001), HPV-related knowledge (p < 0.001), and VFC
      provider status (p < 0.001), among others. Only 39% of physicians reported
      engaging in >=1 AFIX activity. In the stratified multivariable model for
      pediatricians, AFIX activity was significantly associated with HPV-related
      knowledge (aOR = 1.33;95%CI = 1.08-1.63) and provider use of vaccine reminder
      prompts (aOR = 3.61;95%CI = 1.02-12.77). For family medicine physicians, HPV
      related knowledge was significant (aOR = 1.57;95%CI = 1.20-2.05) as was majority
      race of patient population (non-Hispanic White vs. Other: aOR = 3.02;95%CI = 1.08
      8.43), daily patient load (<20 vs. 20-24: aOR = 9.05;95%CI = 2.72-30.10), and
      vaccine administration to male patients (aOR = 2.98;95%CI = 1.11-8.02). Fewer
      than half of Florida pediatric and family medicine physicians engaged in any AFIX
      activities. Future interventions to increase AFIX engagement should focus on
      implementing and evaluating AFIX activities in groups identified as having low
      engagement in AFIX activities.

PMID- 30219691
TI  - Association of oral contraceptive use with suicidal behavior among representative
      Korean population: Results from Korea National Health and Nutrition Examination
      Survey (2007-2016).
AB  - INTRODUCTION: The association of suicide with the use of oral contraceptives (OC)
      is unknown in the Asian population. We aimed to evaluate the association of OC
      use and suicidal behavior in a nationally representative population of Korean
      women. METHOD: Of the 44,501 women who participated in the Korea National Health
      and Nutrition Examination Survey (KNHANES) (2007-2016), 27,067 women aged 20
      years or older who had completed information on OC use and suicidal behavior were
      included. Women with a history of cancer were excluded. Compared to non-users of
      OC, odds ratios (ORs) for suicide attempt/ideation were calculated using a
      multivariable logistic regression among OC users, with testing of the interaction
      term of OC use and history of depression. We also conducted a stratified analysis
      by history of depression. RESULTS: A total of 4,067 women (14.0%) reported they
      had suicide ideations or had attempted suicide, respectively. OC use was
      associated with an increased prevalence of suicidality (OR = 1.13, 95% CI 1.00
      1.24) after adjustments for age, demographic factors, age of menarche, and
      lifestyle behaviors. When stratified by history of depression diagnosis, ORs
      linearly increased as the total duration of OC use lengthened among women with a
      history of depression; however, women without a history of depression showed
      peaked OR at 4- to 12-month use. CONCLUSION: There is an increased association
      between OC use and suicidality and the pattern of the relationship differs
      depending on whether there is a history of depression.

PMID- 30219690
TI  - GWAS and systems biology analysis of depressive symptoms among smokers from the
      COPDGene cohort.
AB  - BACKGROUND: Large sample GWAS is needed to identify genetic factors associated
      with depression. This study used genome-wide genotypic and phenotypic data from
      the COPDGene study to identify genetic risk factors for depression. METHODS: Data
      were from 9716 COPDGene subjects with >=10 pack-year history. Depression was
      defined as antidepressant use and/or a HADS depression subscale score >=8. Non
      Hispanic White (6576) and African-American (3140) subsets were analyzed. A GWAS
      pipeline identified SNPs associated with depression in each group. Network
      analysis software analyzed gene interactions through common biological pathways,
      genetic interactions, and tissue-specific gene expression. RESULTS: The mean age
      was 59.4 years (SD 9.0) with 46.5% female subjects. Depression was in 24.7% of
      the NHW group (1622) and 12.5% of the AA group (391). No SNPs had genome-wide
      significance. One of the top SNPs, rs12036147 (p = 1.28 * 10-6), is near CHRM3.
      Another SNP was near MDGA2 (rs17118176, p = 3.52 * 10-6). Top genes formed
      networks for synaptic transmission with a statistically significant level of more
      co-expression in brain than other tissues, particularly in the basal ganglia (p =
      1.00 * 10-4). LIMITATIONS: Limitations included a depression definition based on
      antidepressant use and a limited HADS score subgroup, which could increase false
      negatives in depressed patients not on antidepressants. Antidepressants used for
      smoking cessation in non-depressed patients could lead to false positives.
      CONCLUSIONS: Systems biology analysis identified statistically significant
      pathways whereby multiple genes influence depression. The gene set pathway
      analysis and COPDGene data can help investigate depression in future studies.

PMID- 30219692
TI  - Adherence to ursodeoxycholic acid therapy in patients with cholestatic and
      autoimmune liver disease.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) is used for treatment of cholestatic
      liver diseases and may improve long-term outcome. Although treatment with this
      hydrophilic bile acid is virtually without side effects, medication adherence
      might be suboptimal due to patient misconceptions, compromising clinical outcome.
      Our aim was to evaluate adherence to UDCA in relation to patient beliefs about
      medicine and to identify potential predictors of poor adherence. METHODS:
      Prospective open-label study recruiting patients in treatment with UDCA from
      April 2016 to March 2017. Adherence was assessed both by the Sensemedic dispenser
      and by patient-reported adherence, during 12 weeks. Good adherence was defined as
      >= 80% intake. Quality of life (by SF-36) and beliefs about medicine (by BMQ)
      were also assessed. RESULTS: A total of 75 patients were enrolled (32% primary
      biliary cholangitis, 31% autoimmune hepatitis, 29% primary sclerosing cholangitis
      and 8% other conditions). Average adherence according to the medication dispenser
      was 92 +/- 16% (range: 17-100). Eighty-nine percent of the patients exhibited
      good adherence and 11% poor adherence. According to the BMQ, 42% of all patients
      were accepting, 50% ambivalent, 8% indifferent and 0% skeptical to UDCA
      treatment. Poor adherence was associated with young age (P = 0.029) and male
      gender (P = 0.021). CONCLUSIONS: Despite the excellent safety profile of UDCA,
      still a significant number of patients are poorly adherent. Young age and male
      sex are associated with poor adherence. Efforts should be made to identify
      patients with poor adherence and to improve their compliance to therapy.

PMID- 30219693
TI  - Elevated lactate impairs the efficacy of antiviral treatment on post-hepatectomy
      survival for advanced stage hepatitis B virus - related hepatocellular carcinoma.
AB  - BACKGROUND: Nucleoside and nucleotide analogues (NAs) have a risk of
      mitochondrial toxicity and then inducing the increase of lactate. We aim to
      evaluate the impact of lactate on the effects of NAs therapy in hepatitis B virus
      related hepatocellular carcinoma (HCC) patients after curative liver resection.
      MATERIALS AND METHODS: Five hundred and fifty-seven HBV-related HCC patients were
      divided into the treatment and control group according to whether they received
      NAs therapy or not. Perioperative and prognosis data were retrospectively
      reviewed. RESULTS: The treatment group had a better overall survival rate (OS)
      than the control group (P = 0.017). The recurrence-free survival rate (RFS) did
      not significantly differ between the two groups (P = 0.174). NAs could improve
      the OS of early stage HCC patients (P = 0.028), as well as the OS of advanced
      stage HCC patients with low level of lactate in subgroup analysis stratified
      against the level of lactate (P = 0.037). Advanced stage HCC patients in the
      treatment group had a higher value of lactate than those in the control group (P
      = 0.024). Besides, advanced stage HCC patients had a higher value of lactate than
      early stage HCC patients in the treatment group (P < 0.001), as well as in the
      control group (P < 0.001). CONCLUSIONS: NAs could improve the long-term outcomes
      of HBV-related HCC patients after curative liver resection. However, the
      improvement effect of NAs therapy is counteracted by the adverse effect of
      elevated lactate in advanced stage HBV-related HCC patients.

PMID- 30219694
TI  - Diagnostic and prognostic value of serum L1-cell adhesion molecule in esophageal
      squamous cell carcinoma.
AB  - OBJECTIVE: L1 cell adhesion molecule (L1CAM) has been found to be dysregulated in
      several types of human cancers. Here, we aimed to determine the level of soluble
      L1CAM in serum of patients with esophageal squamous cell carcinoma (ESCC).
      METHODS: Serum levels of L1CAM were determined by an enzyme-linked immunosorbent
      assay (ELISA) in 191 patients with ESCC and 94 normal controls. Receiver
      operating characteristics (ROC) was employed to calculate diagnostic accuracy.
      Cumulative survival time was calculated by the Kaplan-Meier method and analyzed
      by the logrank test. RESULTS: Levels of L1CAM were significantly lower in all
      ESCC patients than in normal controls (P < 0.001). Detection of serum L1CAM
      provided a sensitivity of 28.3%, a specificity of 90.4% and an area under the
      curve (AUC) of 0.644 (95% CI: 0.579-0.710) in diagnosing ESCC. Similar results
      were observed in the diagnosis of early-stage ESCC (26.2% sensitivity, 90.4%
      specificity, and an AUC of 0.629). Moreover, decreased level of L1CAM was
      correlated with depth of tumor invasion (P < 0.05). Kaplan-Meier analysis showed
      that lower serum L1CAM level was significantly related to shorter overall
      survival time (P = 0.036) and disease-free survival time (P = 0.021) of ESCC
      patients. CONCLUSIONS: Our study demonstrated that serum L1CAM might serve as a
      potential biomarker for the diagnosis and prognosis of ESCC.

PMID- 30219695
TI  - Oral administration of the casein kinase 2 inhibitor TBB leads to persistent
      KCa2.2 channel up-regulation in the epileptic CA1 area and cortex, but lacks anti
      seizure efficacy in the pilocarpine epilepsy model.
AB  - Temporal lobe epilepsy (TLE) is the most common epileptic syndrome in adults and
      often presents with seizures that prove intractable with currently available
      anticonvulsants. Thus, there is still a need for new anti-seizure drugs in this
      condition. Recently, we found that the casein kinase 2 inhibitor 4,5,6,7
      tetrabromotriazole (TBB) prevented the emergence of spontaneous epileptic
      discharges in an acute in vitro epilepsy model. This prompted us to study the
      anti-seizure effects of TBB in the pilocarpine model of chronic epilepsy in vivo.
      To this end, we performed long-term video-EEG monitoring lasting 78-167 days of
      nine chronically epileptic rats and obtained a baseline seizure rate of 3.3 +/-
      1.3 per day (baseline of 27-80 days). We found a significant age effect with more
      pronounced seizure rates in older animals as compared to younger ones. However,
      the seizure rate increased to 6.3 +/- 2.2 per day during the oral TBB
      administration (treatment period of 21-50 days), and following discontinuation of
      TBB, this rate remained stable with 5.2 +/- 1.4 seizures per day (follow-up of 30
      55 days). After completing the video-EEG during the follow-up the hippocampal
      tissue was prepared and studied for the expression of the Ca2+-activated K+
      channel KCa2.2. We found a significant up-regulation of KCa2.2 in the epileptic
      CA1 region and in the neocortex, but in no other hippocampal subfield. Hence, our
      findings indicate that oral administration of TBB leads to persistent up
      regulation of KCa2.2 in the epileptic CA1 subfield and in the neocortex, but
      lacks anti-seizure efficacy in the pilocarpine epilepsy model.

PMID- 30219697
TI  - A systematic review of the experiences of vulnerable people participating in
      research on sensitive topics.
AB  - OBJECTIVE: The aim of this paper is to systematically review studies that discuss
      the experiences of vulnerable populations participating in research on sensitive
      topics. DESIGN: Systematic review performed according to PRISMA guidelines. DATA
      SOURCES: Thirteen databases were searched, locating 197 articles. Following
      removal of duplicates, screening and full text review, 31 studies remained to be
      critically appraised. REVIEW METHODS: As there was a mix of qualitative and
      quantitative articles, the Critical Appraisal Skills Program (CASP) toolkit and
      Effective Public Health Practice Project (EPHPP) tool were used to appraise the
      methodological quality of the articles. Following critical appraisal, the
      remaining 11 articles were synthesised narratively to identify common themes
      across the studies. RESULTS: Despite some reports of distress, responses from
      participants were overwhelmingly positive. There was a strong link between
      symptomatology and potential for distress; however, the majority of those who did
      experience some level of discomfort stated they would still participate in future
      research. Three major themes were extracted: "It was worth it"; "Even if it hurt,
      I would do it again" and "Risk or benefit: fixing the location on the continuum".
      CONCLUSION: Although researchers frequently experience obstacles and the
      phenomenon known as "gatekeeping" when attempting to conduct research amongst
      vulnerable populations, there is little evidence of harm to participants. On the
      contrary, there is evidence of benefit for participants and evidence that they
      are willing to participate if given the opportunity. Although well-meaning, the
      actions of gatekeepers are not only paternalistic, they could be further
      marginalising vulnerable populations by denying them the benefits to be gained
      from research designed to identify and begin addressing their needs.

PMID- 30219696
TI  - Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma
      Cells Using FDA-Approved Drugs.
AB  - The most common primary central nervous system tumor in adults is the
      glioblastoma multiforme (GBM). The highly invasive nature of GBM cells is a
      significant factor resulting in the inevitable tumor recurrence and poor patient
      prognosis. Tumor cells utilize structures known as invadopodia to faciliate their
      invasive phenotype. In this study, utilizing an array of techniques, including
      gelatin matrix degradation assays, we show that GBM cell lines can form
      functional gelatin matrix degrading invadopodia and secrete matrix
      metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading
      enzyme. Furthermore, these cellular activities were augmented in cells that
      survived radiotherapy and temozolomide treatment, indicating that surviving cells
      may possess a more invasive phenotype posttherapy. We performed a screen of FDA
      approved agents not previously used for treating GBM patients with the aim of
      investigating their "anti-invadopodia" and cytotoxic effects in GBM cell lines
      and identified a number that reduced cell viability, as well as agents which also
      reduced invadopodia activity. Importantly, two of these, pacilitaxel and
      vinorelbine tartrate, reduced radiation/temozolomide-induced invadopodia
      activity. Our data demonstrate the value of testing previously approved drugs
      (repurposing) as potential adjuvant agents for the treatment of GBM patients to
      reduce invadopodia activity, inhibit GBM cell invasion, and potentially improve
      patient outcome.

PMID- 30219698
TI  - The Impact of Advanced Patient Age on Mortality after Allogeneic Hematopoietic
      Cell Transplantation for Non-Hodgkin Lymphoma: A Retrospective Study by the
      European Society for Blood and Marrow Transplantation Lymphoma Working Party.
AB  - More than 60% of patients with non-Hodgkin lymphoma (NHL) are age >60 years at
      presentation. The purpose of this study was to compare the potential risks and
      benefits of allogeneic hematopoietic cell transplantation (alloHCT) in elderly
      patients with NHL with younger patients in a large sample, also taking into
      account comorbidity information. All patients age >=18 years who had undergone
      alloHCT from a matched sibling or unrelated donor for NHL between 2003 and 2013
      and were registered with the European Society for Blood and Marrow
      Transplantation were eligible for the study. The primary study endpoint was 1
      year nonrelapse mortality (NRM). A total of 3919 patients were eligible and were
      categorized by age: young (Y), 18 to 50 y (n = 1772); middle age (MA), 51 to 65 y
      (n = 1967); or old (O), 66 to 77 y (n = 180). Follicular lymphoma was present in
      37% of the patients; diffuse large B cell lymphoma, in 30%; mantle cell lymphoma,
      in 21%, and peripheral T cell lymphoma, in 11%. At the time of alloHCT, 85% of
      the patients were chemosensitive and 15% were chemorefractory. With a median
      follow-up of 4.5 years in survivors, NRM at 1 year was 13% for the Y group. 20%
      for the MA group, and 33% for the O group (P <.001), whereas relapse incidence
      and overall survival (OS) at 3 years in the 3 groups were 30%, 31%, and 28% (P =
      .355) and 60%, 54%, and 38% (P <.001), respectively. Multivariable adjustment for
      confounders, including sex, NHL subset, time from diagnosis, chemosensitivity,
      donor, and conditioning, confirmed older age as a significant predictor for NRM
      and OS, but not for relapse risk. Although comorbidity was a significant
      predictor of NRM in a subset analysis restricted to the 979 patients with
      comorbidity information available, age retained its significant impact on NRM. In
      conclusion, our data show that alloHCT in patients age >65 y provides similar NHL
      control as seen in younger patients but is associated with a higher NRM that is
      not fully explained by comorbidity. Thus, although alloHCT is feasible and
      effective in very old patients, the increased NRM risk must be taken into account
      when assessing the indication for alloHCT for NHL in this age group.

PMID- 30219699
TI  - Mobilization of Hematopoietic Progenitor Cells for Autologous Transplantation
      Using Pegfilgrastim and Plerixafor: Efficacy and Cost Implications.
AB  - Filgrastim (FIL) is the most common growth factor combined with plerixafor for
      autologous hematopoietic progenitor cell mobilization, but requires daily, multi
      injection administration. We adopted a standardized mobilization regimen with
      pegfilgrastim (PEG) and upfront plerixafor, allowing for a single injection given
      the long half-life and slow elimination of PEG. Between 2015 and 2017, a total of
      235 patients with lymphoma or plasma cell dyscrasias underwent mobilization with
      PEG 6 mg on day 1 and upfront plerixafor 24 mg on day 3, followed by apheresis on
      day 4 regardless of peripheral blood CD34+ cells. The median CD34+ cells/mm3 in
      peripheral blood on first day of collection was 48 and median collection yield
      was 7.27 * 106 CD34+ cells/kg (range, 0.32 to 39.6 * 106 CD34+ cells/kg) after a
      mean of 1.6 apheresis collections. Overall, 83% of patients achieved the
      mobilization target, and 95% reached the minimum necessary CD34+ cell yield to
      proceed with transplantation (2 * 106 CD34+ cells/kg). Because FIL is weight
      based and dosed daily, the cost comparison with PEG is influenced by patient
      weight and number of apheresis sessions required. A cost simulation using actual
      patient data indicates that PEG is associated with lower cost than FIL for the
      majority of patients. Autologous hematopoietic progenitor cell mobilization with
      PEG and plerixafor is practical, effective, and not associated with increased
      cost compared with FIL mobilization.

PMID- 30219700
TI  - The Anatomic Distribution of Skin Involvement in Patients with Incident Chronic
      Graft-versus-Host Disease.
AB  - Little is known about the anatomic distribution of cutaneous chronic graft-versus
      host disease (cGVHD). Using data from the cGVHD Consortium Improving Outcomes
      Assessment Study, we describe the frequency and extent of erythema and
      superficial and deep sclerosis in 8 anatomic sites in patients with incident
      disease (ie, new cGVHD diagnosis within 3 months of study entry) receiving
      systemic therapy. Of 339 patients with incident disease, 182 (54%) had skin
      involvement. When an extremity was involved, the same type of disease was present
      contralaterally in 92% of cases, revealing a high level of symmetry. As
      anticipated, erythema was the most common incident feature; however, sclerotic
      skin involvement at the time of cGVHD diagnosis was more common than has been
      suggested by previous studies. Erythema occurred in 155 (85%) and sclerosis in 53
      (29%) of the patients with skin involvement (46% and 16%, respectively, of the
      entire cohort of 339 incident cGVHD cases). Erythema was least common on the
      lower extremities (n = 71; 39% of patients with skin involvement). Moveable
      sclerosis was rare on the head, neck, and scalp (n = 4; 2%). Deep sclerosis did
      not occur in this region, and instead was most likely to occur on the upper
      extremities (n = 14; 8%) and lower extremities (n = 14; 8%). More than one-half
      of patients with erythema (n = 107; 58.7%) had diffuse involvement (4 or more of
      8 sites involved), compared with less than one-third of those with sclerosis (n =
      16; 30.2%).

PMID- 30219701
TI  - Highly sensitive and accurate estimation of bloodstain age using smartphone.
AB  - The estimation of bloodstain age is an important factor in forensic analysis.
      Previously, we have reported a smartphone-based colorimetric system for age
      estimation of bloodstain, in which Whole blood and EDTA whole blood were dropped
      on 4 different materials (700 MUL) and captured using a smartphone for 72 h. In
      order to enhance sensitivity and accuracy of the previous system, the current
      work is dedicated towards the application of pattern recognition and
      classification of bloodstain images based on a smartphone. Three detection
      methods (blood pool, crack ratio, and colorimetric analysis) in terms of 6 steps
      of drying process of the bloodstain (coagulation, gelation, edge desiccation,
      center desiccation, crack propagation, and final desiccation) were applied to
      estimate age of the bloodstain accurately. Three parameters from the bloodstain
      images were then classified as comparing to those of stored reference images with
      similar trends in database. The bloodstain age was successfully determined by 9
      h, 18 h, and 48 h with respect to the three detection methods mentioned above,
      respectively. The differences in bloodstain images were clearly distinguished
      every hour by using smartphone-based pattern recognition analysis. Therefore, our
      system is expected to shed a light on the field of forensic science by estimating
      bloodstain age in real time.

PMID- 30219702
TI  - Proteomic strategies to unravel age-related redox signalling defects in skeletal
      muscle.
AB  - Increased oxidative damage and disrupted redox signalling are consistently
      associated with age-related loss of skeletal muscle mass and function. Redox
      signalling can directly regulate biogenesis and degradation pathways and
      indirectly via activation of key transcription factors. Contracting skeletal
      muscle fibres endogenously generate free radicals (e.g. superoxide) and non
      radical derivatives (e.g. hydrogen peroxide). Exercise induced redox signalling
      can promote beneficial adaptive responses that are disrupted by age-related redox
      changes. Identifying and quantifying the redox signalling pathways responsible
      for successful adaptation to exercise makes skeletal muscle an attractive
      physiological model for redox proteomic approaches. Site specific identification
      of the redox modification and quantification of site occupancy in the context of
      protein abundance remains a crucial concept for redox proteomics approaches.
      Notwithstanding, the technical limitations associated with skeletal muscle for
      proteomic analysis, we discuss current approaches for the identification and
      quantification of transient and stable redox modifications that have been
      employed to date in ageing research. We also discuss recent developments in
      proteomic approaches in skeletal muscle and potential implications and
      opportunities for investigating disrupted redox signalling in skeletal muscle
      ageing.

PMID- 30219703
TI  - Modelling the role of redox-related mechanisms in musculoskeletal ageing.
AB  - The decline in the musculoskeletal system with age is driven at the cellular
      level by random molecular damage. Cells possess mechanisms to repair or remove
      damage and many of the pathways involved in this response are regulated by redox
      signals. However, with ageing there is an increase in oxidative stress which can
      lead to chronic inflammation and disruption of redox signalling pathways. The
      complexity of the processes involved has led to the use of computational
      modelling to help increase our understanding of the system, test hypotheses and
      make testable predictions. This paper will give a brief background of the
      biological systems that have been modelled, an introduction to computational
      modelling, a review of models that involve redox-related mechanisms that are
      applicable to musculoskeletal ageing, and finally a discussion of the future
      potential for modelling in this field.

PMID- 30219704
TI  - Role of GPX4 in ferroptosis and its pharmacological implication.
AB  - Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent
      lipid peroxidation and metabolic constraints. Dependence on NADPH/H+,
      polyunsaturated fatty acid metabolism, and the mevalonate and glutaminolysis
      metabolic pathways have been implicated in this novel form of regulated necrotic
      cell death. Genetic studies performed in cells and mice established the
      selenoenzyme glutathione peroxidase (GPX4) as the key regulator of this form of
      cell death. Besides these genetic models, the identification of a series of small
      molecule ferroptosis-specific inhibitors and inducers have not only helped in the
      delineation of the molecular underpinnings of ferroptosis but they might also
      prove highly beneficial when tipping the balance between cell death inhibition
      and induction in the context of degenerative diseases and cancer, respectively.
      In the latter, the recent recognition that a subset of cancer cell lines
      including certain triple negative breast cancer cells and those of therapy
      resistant high-mesenchymal cell state present a high dependence on this lipid
      make-up offers unprecedented opportunities to eradicate difficult to treat
      cancers. Due to the rapidly growing interest in this form of cell death, we
      provide an overview herein what we know about this field today and its future
      translational impact.

PMID- 30219705
TI  - Impact of doxofylline compared to theophylline in asthma: A pooled analysis of
      functional and clinical outcomes from two multicentre, double-blind, randomized
      studies (DOROTHEO 1 and DOROTHEO 2).
AB  - This pooled analysis of double-blind, randomized, placebo-controlled trials aimed
      to investigate the impact of DOxofylline compaRed tO THEOphylline (DOROTHEO 1 and
      DOROTHEO 2 studies) on functional and clinical outcomes in asthma. Asthmatic
      patients >=16 years of age with forced expiratory volume in 1 s (FEV1) >=50% and
      <80% and with >=15% post-bronchodilator increase in FEV1 were randomized in a
      1:1:1:1 ratio in DOROTHEO 1 to receive doxofylline 200 mg, doxofylline 400 mg,
      theophylline 250 mg, or placebo; in DOROTHEO 2 patients were randomized in a
      1:1:1 ratio to receive doxofylline 400 mg, theophylline 250 mg, or placebo. All
      double-blind treatments were taken orally with immediate release formulations and
      three times daily. Data evaluating the effect of doxofylline 400 mg, theophylline
      250 mg and placebo on FEV1, asthma events rate, use of salbutamol as rescue
      medication and adverse events (AEs) were pooled from both studies. The pooled
      analysis of 483 patients demonstrated that both doxofylline 400 mg and
      theophylline 250 mg significantly increased FEV1, reduced the rate of asthma
      events and use of salbutamol to relieve asthma symptoms compared to placebo (p <
      0.01). No significant differences were detected between doxofylline 400 mg and
      theophylline 250 mg. Doxofylline 400 mg did not significantly (p > 0.05) increase
      the risk of AEs compared to placebo, conversely in patients treated with
      theophylline 250 mg the risk of AEs was significantly (p < 0.05) greater than in
      those that received placebo. We conclude that doxofylline seems to offer a
      promising alternative to theophylline with a superior efficacy/safety profile in
      the management of patients with asthma.

PMID- 30219707
TI  - A qPCR assay for measuring the post-integrational DNA repair in HIV-1
      replication.
AB  - The post-integrational gap repair is a critical and poorly studied stage of the
      lentiviral life cycle. It might be performed by various cellular DNA repair
      pathways but the exact mechanism of the repair process has not yet been
      described. One of the reasons for that is the lack of a functional quantitative
      assay that could precisely measure the amount of integrated viral DNA that has
      completed the post-integrational gap repair stage. Here, we present an approach
      that is based on a widely used Alu-specific PCR for the estimation of integrated
      viral DNA but includes several steps that allow discrimination between integrated
      repaired and integrated-unrepaired viral DNA forms. We used the approach for the
      estimation of the kinetics of gap repair in a viral vector system and showed that
      the gap repair process starts at 17 h post infection and lasts 10 more hours. We
      also showed that the addition of Nu7441 - a small molecule inhibitor of DNA
      breaks sensor kinase in the non-homologous end joining DNA repair pathway -
      specifically inhibits the gap repair process while having no influence on the
      integration itself.

PMID- 30219706
TI  - PDZ-RhoGEF Is a Signaling Effector for TROY-Induced Glioblastoma Cell Invasion
      and Survival.
AB  - Glioblastoma multiforme (GBM) is the most common type of malignant brain tumors
      in adults and has a dismal prognosis. The highly aggressive invasion of malignant
      cells into the normal brain parenchyma renders complete surgical resection of GBM
      tumors impossible, increases resistance to therapeutic treatment, and leads to
      near-universal tumor recurrence. We have previously demonstrated that TROY
      (TNFRSF19) plays an important role in glioblastoma cell invasion and therapeutic
      resistance. However, the potential downstream effectors of TROY signaling have
      not been fully characterized. Here, we identified PDZ-RhoGEF as a binding partner
      for TROY that potentiated TROY-induced nuclear factor kappa B activation which is
      necessary for both cell invasion and survival. In addition, PDZ-RhoGEF also
      interacts with Pyk2, indicating that PDZ-RhoGEF is a component of a signalsome
      that includes TROY and Pyk2. PDZ-RhoGEF is overexpressed in glioblastoma tumors
      and stimulates glioma cell invasion via Rho activation. Increased PDZ-RhoGEF
      expression enhanced TROY-induced glioma cell migration. Conversely, silencing PDZ
      RhoGEF expression inhibited TROY-induced glioma cell migration, increased
      sensitivity to temozolomide treatment, and extended survival of orthotopic
      xenograft mice. Furthermore, depletion of RhoC or RhoA inhibited TROY- and PDZ
      RhoGEF-induced cell migration. Mechanistically, increased TROY expression
      stimulated Rho activation, and depletion of PDZ-RhoGEF expression reduced this
      activation. Taken together, these data suggest that PDZ-RhoGEF plays an important
      role in TROY signaling and provides insights into a potential node of
      vulnerability to limit GBM cell invasion and decrease therapeutic resistance.

PMID- 30219708
TI  - Impact of Surgical Experience on Radiation Exposure during Retrograde Intrarenal
      Surgery: A Propensity-Score Matching Analysis.
AB  - BACKGROUND: The impact of surgical experience on radiation exposure (RE) during
      endourological procedures has been poorly investigated. OBJECTIVE: To assess the
      impact of surgical experience on fluoroscopy time (FT) and RE during retrograde
      intrarenal surgery (RIRS). DESIGN, SETTING, AND PARTICIPANTS: The study included
      140 patients who underwent RIRS performed either by a senior surgeon (expertise
      of >100 RIRSs) (group A) or by two junior residents (expertise of <15 RIRSs)
      (group B) between January 2016 and May 2018. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: We tested the hypothesis that surgical experience had a limited impact
      on RE during RIRS. To adjust for potential baseline confounders, propensity-score
      matching was performed. Descriptive statistics and linear regression models
      tested the association between clinical variables and FT and patients' effective
      doses. RESULTS AND LIMITATIONS: There was no significant difference between the
      two groups for baseline, intraoperative, and postoperative characteristics.
      Overall FT (p=0.97) and effective dose (p=0.79) did not differ between groups. A
      statistically significant association was found between male sex (all p<0.03),
      stone burden (all p<0.001), operative time (all p<0.003), and postoperative
      double-J placement (all p<0.02) with both FT and effective dose. Linear
      multivariable analysis revealed that body mass index was significantly associated
      with effective dose (p=0.002). Similarly, longer operative time (all p<0.03) and
      double-J placement (all p<0.04) were significantly associated with increased FT
      and effective dose. CONCLUSIONS: Surgical experience has a limited impact on FT
      and RE during RIRS. Longer operative time and double-J placement were associated
      with increased FT and effective dose. PATIENT SUMMARY: In this study, we assessed
      whether surgical experience affects fluoroscopy time and patient's effective dose
      during retrograde intrarenal surgery (RIRS). We found that radiation exposure
      (RE) was not affected by surgeon's experience and that the standardisation of the
      surgical technique at the beginning of the learning curve of young surgeons may
      represent the key factor in reducing RE during RIRS.

PMID- 30219709
TI  - Perceptions of Prostate MRI and Fusion Biopsy of Radiation Oncologists and
      Urologists for Patients Diagnosed with Prostate Cancer: Results from a National
      Survey.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) of the prostate and fusion biopsy
      have been advanced to improve the detection of clinically significant prostate
      cancer (PCa). Yet, frequency of their use and contemporary attitudes among
      radiation oncologists (ROs) and urologists (UROs) remain largely unknown.
      OBJECTIVE: We performed a national survey of UROs and ROs to assess the perceived
      attitudes towards and frequency of prostate MRI and fusion biopsy. DESIGN,
      SETTING, AND PARTICIPANTS: We conducted a national survey of 915 ROs and 940 UROs
      about prostate MRI and fusion biopsy in 2017. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: The survey queried respondents about perceptions of
      prostate MRI and fusion biopsy and inquired about self-reported utilization.
      Pearson chi-square test and multivariable logistic regression were used to
      identify physician characteristics associated with survey responses. RESULTS AND
      LIMITATIONS: The overall response rate was 37% (n=691). Both UROs and ROs
      demonstrated similar positive views that MRI with fusion biopsy improves PCa risk
      stratification (67% vs 71%; p=0.19) and fusion biopsy increases the confidence
      recommending active surveillance (55% vs 60%; p=0.18). Yet, only a quarter of
      both specialties reported frequent use of prostate MRI for treatment decisions
      for low- and intermediate-risk PCa. Compared with respondents practicing in
      community practices, those in academic practices were more likely to report using
      prostate MRI for low- (44% vs 19%; adjusted odds ratio [OR]: 3.96; p<0.001) and
      intermediate-risk PCa (42% vs 24%; adjusted OR: 2.49; p<0.001). Our study was
      limited by a modestly lower response rate. CONCLUSIONS: While both specialties
      have perceived value in favor of prostate MRI and fusion biopsy, only a quarter
      of respondents report their use in clinical practice. Physicians practicing in
      academic medical centers had greater self-reported use. PATIENT SUMMARY: Magnetic
      resonance imaging of the prostate and targeted biopsies have growing evidence of
      their use as a superior diagnostic methodology for prostate cancer diagnosis and
      treatment decisions. Our survey study found that a majority of radiation
      oncologists and urologists view both favorably in improving prostate cancer
      detection and treatment decisions. Yet, only a quarter report using it in routine
      clinical practice for men diagnosed with prostate cancer.

PMID- 30219710
TI  - Intramuscular Immunization Induces Antigen-specific Antibodies in Urine.
AB  - : Towards the development of vaccines against urinary tract infections (UTI), we
      determined the ability of intramuscular (i.m.) immunization to result in antigen
      specific antibodies in urine. As a model antigen/vaccine, levels of total and
      vaccine-specific antibodies were determined in urine as a spin-out study of a
      phase 1 trial. Non-muscle-invasive bladder cancer (NMIBC) patients at different
      risks of progression, undergoing intravesical bacillus Calmette-Guerin (BCG)
      immunotherapy or not, received an adjuvanted recombinant protein vaccine that
      resulted in high titers of vaccine-specific serum immunoglobulin G (IgG) in all
      patients, regardless of the risk group. Vaccine-specific IgG and immunoglobulin A
      (IgA) were detected in urine of half of the patients at low risk of progression
      NMIBC and in all the intermediary/high- (int/high) risk patients. Vaccine
      specific IgG titers were correlated to total urinary IgG levels, the latter being
      higher in the int/high-risk patients. In contrast, vaccine-specific IgA did not
      correlate to urinary IgA levels. Furthermore, vaccine-specific antibodies were
      transiently increased by intravesical BCG instillations. Altogether, our data
      show that a standard i.m. immunization can effectively induce antigen-specific
      antibodies in urine, which, upon selection of optimal vaccine targets, may
      provide protection against UTI. Vaccine-specific IgG titers were dependent on
      conditions affecting total urinary IgG levels, while production of vaccine
      specific IgA in situ might independently contribute to protection against
      infections in the bladder. PATIENT SUMMARY: Towards the development of vaccines
      able to protect against urinary tract infections, we examined the potential of
      the intramuscular vaccination using a model antigen. We found two types of
      specific antibodies in the urine, which together may locally contribute to
      protection against infections, thus supporting the use of such a standard
      immunization route.

PMID- 30219711
TI  - Outcomes of Elective Ureteroscopy for Ureteric Stones in Patients with Prior
      Urosepsis and Emergency Drainage: Prospective Study over 5 yr from a Tertiary
      Endourology Centre.
AB  - BACKGROUND: Elective treatment of ureteric stones is needed after emergency
      drainage of urosepsis. OBJECTIVE: We wanted to look at the outcomes of elective
      ureteroscopic stone treatment in patients with prior sepsis and emergency
      drainage via retrograde ureteric stent (RUS) or percutaneous nephrostomy (PCN).
      DESIGN, SETTING, AND PARTICIPANTS: Data of all patients who underwent elective
      ureteroscopy (URS) for stone disease over 5 yr (March 2012-December 2016) were
      prospectively collected. INTERVENTION: Elective URS following previous emergency
      RUS or PCN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were collated
      for consecutive patients who underwent emergency drainage for urosepsis secondary
      to stone disease, followed by elective URS. Data was collected regarding patient
      demographics, stone parameters, and clinical outcomes. Statistical analysis was
      performed using SPSS version 24. RESULTS AND LIMITATIONS: In total, 76 patients
      underwent 82 elective procedures (six underwent bilateral URS) with a male to
      female ratio of 1:2 and a mean age of 57 yr. Emergency decompression was achieved
      via RUS in 63 (83%) and PCN in 13 (17%) patients. A positive urine culture on
      presentation was obtained in 26 (34%) patients, and 27 (36%) patients were
      admitted to the intensive care unit (ICU). The mean single and overall stone size
      was 8.6 (2-23) and 10.8 (2-32) mm, respectively. The mean operating time was 42
      (5-129) min with stone-free rate (SFR) of 97% (n=74). There were three (4%)
      complications in total, of which two patients developed urinary tract infection
      needing intravenous antibiotics (Clavien II) and a third developed sepsis
      (Clavien IV) needing ICU admission. There was no difference in ureteroscopic
      lithotripsy outcomes (operative time, complications, or SFR) on comparing initial
      RUS or PCN, admission to ICU or ward, positive or negative urine culture result,
      presence of single or multiple stones, and between American Society of
      Anaesthesiologists (ASA) grade of patients. The ASA grade of patients was a
      significant predictor of day case procedures (p=0.001). CONCLUSIONS: Elective URS
      achieved excellent outcomes in patients who previously presented with obstructing
      calculi and sepsis needing emergency decompression. Overnight inpatient admission
      was needed in some patients with a higher ASA grade. PATIENT SUMMARY: In this
      report, we look at the outcomes of planned ureteroscopy procedures for stone
      disease in patients with previous urosepsis. These patients with previous
      emergency drainage for urosepsis had excellent outcomes from their planned
      ureteroscopic surgery. This information will help in preoperative patient
      optimisation and counselling.

PMID- 30219712
TI  - In vitro and in vivo toxic effects and inflammatory responses induced by
      carboxylated black carbon-lead complex exposure.
AB  - Black carbon (BC) is a key component of atmospheric fine particulate matter
      (PM2.5) and it tends to adsorb various pollutants (e.g., heavy metals and
      organics) during atmospheric transport. This adsorption leads to the complexity
      and uncertainty of the source and chemical composition of PM2.5, making the
      toxicologic effects and health risks induced by PM2.5 difficult to determine.
      Here, we used carboxylated black carbon (c-BC) and c-BC-lead complexes (c-BC-Pb)
      to investigate the in vitro and in vivo toxic effects and inflammatory responses.
      The physicochemical properties of c-BC and c-BC-Pb complexes were characterized
      by the transmission electron microscope (TEM), X-ray photoelectron spectroscopy
      (XPS), dynamic light scattering (DLS), and in ductively coupled plasma-atomic
      emission spectra (ICP-AES). Cytotoxicity in vitro showed that the exposure of
      human bronchial epithelial cells (BEAS-2B) to low-dose c-BC-Pb particles
      significantly induced greater toxicity than that of c-BC, suggesting that lead
      (Pb) might play an important role in induced cytotoxicity after combined exposure
      to c-BC-Pb particles. The findings were further confirmed by the results in vivo,
      which indicated that c-BC-Pb particles significantly induced inflammation and
      lung injury. Based on the results of this experiment, the differences in toxicity
      can be attributed to the synergistic effect of Pb on the BC particles, which play
      a synergistic role in vitro and in vivo in the development of toxicity. The c-BC
      Pb particles model used in this study may be helpful for the evaluation of
      cytotoxicity induced by different sources of BC particles or BC-heavy metal
      complexes and provide a new approach for understanding PM2.5-induced toxicity and
      health risks.

PMID- 30219713
TI  - In ovo exposure to triclosan alters the hepatic proteome in chicken embryos.
AB  - The occurrence of triclosan (TCS) in the eggs of wild avian species is an
      emerging concern. We previously evaluated the effects of in ovo exposure to TCS
      on the liver transcriptome of chicken embryos and proposed adverse outcome
      pathways (AOPs). However, the key molecular events identified to be affected need
      to be verified at the protein level. Herein, we investigated the changes in the
      spectrum of hepatic proteins in TCS-treated chicken embryos by proteomic analysis
      to validate the key signaling pathways involved in the AOPs. We identified and
      quantified 894 unique proteins using matrix-assisted laser desorption/ionization
      time-of-flight/time-of-flight tandem mass spectrometry. In the 0.1 (low dose), 1
      (median dose), and 10 MUg triclosan/g egg (high dose) groups, TCS caused
      significant changes in the levels of 195, 233, and 233 proteins in males and 237,
      188, and 156 proteins in females, respectively (fold changes > 1.3 or < 0.7). TCS
      exposure modulated the expression of proteins, predominantly involved in
      signaling pathways of lipid and energy metabolism in both genders. Among the
      proteins associated with TCS metabolism in the liver, phase I (e.g., CYP2C23a)
      and phase II (e.g., UGT1A1) enzymes mediated by chicken xenobiotic receptor, were
      only induced in males. In consonance with the malondialdehyde levels, which were
      increased upon TCS exposure in females in a dose-dependent manner, a battery of
      antioxidant enzymes, notably SOD2, GST, GSTz1, and PRDX1, was decreased and SOD1
      and GSTK1 were increased in the embryos. Taken together, this proteome analysis
      complements the transcriptome profiling reported in our previous study and
      authenticates the AOPs proposed for chicken embryos in ovo exposed to TCS.

PMID- 30219714
TI  - In silico and in vitro screening of small molecule Inhibitors against SYT-SSX1
      fusion protein in synovial sarcoma.
AB  - Synovial sarcoma (SS) is characterized by a tumour specific chromosomal
      translocation t(X;18) (p11;q11) which results in the formation of SYT-SSX1 fusion
      protein. This fusion protein represents a clear therapeutic target and molecules
      specifically targeting SYT-SSX1 fusion protein are currently not available. In
      this study, SYT-SSX1 fusion protein sequence was retrieved from Uniprot and 3D
      structure was generated using I-TASSER modeling program. A structure based
      computational screening approach has been employed using Glide docking software
      to identify potential SYT-SSX1 small molecule inhibitors that bind to the
      junction region of the fusion protein. The obtained inhibitors were further
      filtered based on the docking score and ADME/T properties. Ten best fit compounds
      were chosen for in vitro studies. The anti-proliferative activities of these 10
      compounds were screened in Yamato, ASKA (carries SYT-SSX1 fusion protein) and
      other sarcoma cell lines such as A673, 143B to understand the specificity of
      inhibition of the chosen compounds. The in vitro activity was compared against
      HEK293 cell lines. The compound 5-fluoro-3-(1-phenyl-1H-tetraazol-5-yl)-1H-indole
      (FPTI) was found to be selectively cytotoxic in synovial sarcoma cell lines
      (Yamato and ASKA) and this compound also showed insignificant anti proliferative
      activity on other cell lines. Further, target gene expression study confirmed
      that FPTI treatment down-regulated SYT-SSX1 and modulated its downstream target
      genes. Cell cycle analysis revealed the involvement of an apoptotic mechanism of
      cell death. Further experimental validations may elucidate the therapeutic
      potentials of FPTI against SYT-SSX1 fusion protein.

PMID- 30219715
TI  - Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals
      with CYP2C9*3 variants.
AB  - Celecoxib was characterized as a substrate of human cytochrome P450 (CYP) 2D6 in
      vitro. In recombinant CYP2D6, celecoxib hydroxylation showed atypical substrate
      inhibition kinetics with apparent Km, Ki, and Vmax of 67.2 MUM, 12.6 MUM, and
      1.33 MUM/min, respectively. In human liver microsomes (HLMs), a concentration
      dependent inhibition of celecoxib hydroxylation by quinidine was observed after
      CYP2C9 and CYP3A4 were inhibited. In individual HLMs with variable CYP2D6
      activities, a significant correlation was observed between celecoxib
      hydroxylation and CYP2D6-selective dextromethorphan O-demethylation when CYP2C9
      and CYP3A4 activities were suppressed (r = 0.97, P < 0.0001). Molecular modeling
      showed two predominant docking modes of celecoxib with CYP2D6, resulting in
      either a substrate or an inhibitor. A second allosteric binding antechamber,
      which stabilized the inhibition mode, was revealed. Modeling results were
      consistent with the observed substrate inhibition kinetics. Using HLMs from
      individual donors, the relative contribution of CYP2D6 to celecoxib metabolism
      was found to be highly variable and dependent on CYP2C9 genotypes, ranging from
      no contribution in extensive metabolizers with CYP2C9*1*1 genotype to
      approximately 30% in slow metabolizers with allelic variants CYP2C9*1*3 and
      CYP2C9*3*3. These results demonstrate that celecoxib may become a potential
      victim of CYP2D6-associated drug-drug interactions, particularly in individuals
      with reduced CYP2C9 activity.

PMID- 30219716
TI  - Derivation of human induced pluripotent stem cell line EURACi004-A from skin
      fibroblasts of a patient with Arrhythmogenic Cardiomyopathy carrying the
      heterozygous PKP2 mutation c.2569_3018del50.
AB  - Arrhythmogenic Cardiomyopathy (ACM) is an inherited cardiac disease characterized
      by arrhythmias and fibro-fatty replacement in the ventricular myocardium.
      Causative mutations are mainly reported in desmosomal genes, especially in
      plakophilin2 (PKP2). Here, using a virus-free reprogramming approach, we
      generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of one ACM
      patient carrying the frameshift heterozygous PKP2 mutation c.2569_3018del50. The
      iPSC line (EURACi004-A) showed the typical morphology of pluripotent cells,
      possessed normal karyotype and exhibited pluripotency markers and trilineage
      differentiation potential, including cardiomyogenic capability. Thus, this line
      can represent a human in vitro model to study the molecular basis of ACM.

PMID- 30219717
TI  - Associations of Homer Scaffolding Protein 1 gene and psychological correlates
      with suicide attempts in Chinese: A pilot study of multifactorial risk model.
AB  - BACKGROUND: Suicide is a fatal outcome for subjects with mental ill-health.
      Genetic factors and psychological correlates are believed to contribute to the
      risk of suicide attempts (SA), whereas both factors are reported to exert a small
      effect. This study therefore tried to investigate if combination of the two
      aspects can enhance the explanation of variance in SA. METHODS: A common variant
      rs7713917 in HOMER1 gene was genotyped for 333 Chinese psychiatric patients with
      or without SA. Multifactorial risk models comprised of this variant and
      psychological correlates were identified by logistic regression analysis (LRA)
      and Multifactor Dimensionality Reduction (MDR) method separately, and then
      evaluated for their performance by biostatistical methods. RESULTS: An
      association of A-carrier genotypes in rs7713917 with an increased risk of SA was
      observed (OR = 1.79, 95% CI = 1.08-2.98). Although with a medium effect size,
      this variant alone could only explain 1.9% variance of SA. Interestingly, this
      study was the first time to show that the association of the rs7713917 and SA was
      significantly mediated by the NEO conscientiousness (NEOC) dimension (p-value =
      0.002), with a greater genetic effect observed in subjects with a low NEO-C level
      (OR = 2.89, 95% CI = 1.16-7.18) but not in subjects with an average or high
      level. Upon the LRA method, the multifactorial risk model constituted of the two
      interacted factors and their interaction effect could explain up to 17.0%
      variance, which was almost 9-fold higher than the one explained by the rs7713917
      alone. Furthermore, this model owned a higher effectiveness than the three models
      identified by the MDR method (p-value < 0.0007). CONCLUSIONS: The present study
      identified an effective multifactorial risk model, in which the combination of
      the HOMER1 variant and the NEO-C dimension could enhance explanation of the
      variance of SA in Chinese. This pilot study may provide a novel avenue to
      investigate the pathogenesis of SA in psychiatric patients.

PMID- 30219718
TI  - Differences by sex in associations between injection drug risks and drug crime
      conviction among people who inject drugs in Almaty, Kazakhstan.
AB  - BACKGROUND: The criminalization of drug use leads to high rates of drug crime
      convictions for engaging in injection drug use behaviors, introducing barriers to
      HIV prevention and drug treatment for PWID. Females (FWID) face unique
      vulnerabilities to HIV compared to males (MWID) in Kazakhstan. This study
      examined sex differences in associations between HIV/HCV infection, HIV
      knowledge, injection drug risk behaviors, and conviction for a drug crime in a
      sample of people who inject drugs (PWID) in Almaty, Kazakhstan. METHODS: Analyses
      were performed on baseline data from 510 PWID and stratified by males (MWID)
      (329) and females (FWID) (181) from Kazakhstan in a couples-focused HIV
      prevention intervention. Logistic regression analyses using mixed effects (AOR)
      examined associations between HIV/HCV infection, HIV knowledge, injection drug
      risk behaviors, drug use severity, drug treatment history and conviction for a
      drug crime. RESULTS: About three quarters of PWID reported drug crime conviction
      (73.92%, n = 377). HCV infection was associated with increased odds of drug crime
      conviction for FWID (AOR = 4.35, CI95 = 1.83-10.31, p < .01) and MWID (AOR =
      3.62, CI95 = 1.09-12.07, p < .01). HIV transmission knowledge was associated with
      increased odds of conviction for MWID (AOR = 1.19, CI95 = 1.00-1.41, p < .05).
      Injection drug risk knowledge was associated with lower odds of conviction (AOR =
      .75, CI95 = .59-.94, p < .05) for FWID. Receptive syringe sharing (AOR = 3.48,
      CI95 = 1.65-7.31, p < .01), splitting drug solutions (AOR = 4.12, CI95 = 1.86
      7.31, p < .05), and injecting with more than two partners (AOR = 1.89, CI95 =
      1.06-3.34, p < .05) was associated with increased odds of conviction for FWID.
      Receptive syringe or equipment sharing with intimate partners was associated with
      conviction for both MWID (AOR = 1.90, CI95 = 1.03-3.92, p < .05) and FWID (AOR =
      1.95, CI95 = 1.02-3.70, p < .05). For FWID, injection drug use in public spaces
      was associated with conviction (AORME = 3.25, CI95 = 1.31-7.39, p < .01). Drug
      use severity was associated with increased odds of conviction for FWID (AOR =
      1.29, CI95 = 1.09-1.53, p < .001) and MWID (AOR = 1.24, CI95 = 1.09-1.41, p <
      .001). Ever receiving drug treatment was associated with conviction for MWID (AOR
      = 2.31, CI95 = 1.32-4.12, p < .01). CONCLUSION: High-risk behaviors, HCV
      infection and more severe substance use disorders are associated with drug crime
      conviction for PWID, particularly FWID. Structural interventions are necessary to
      increase the engagement of PWID with drug crime convictions in HIV prevention and
      substance abuse treatment.

PMID- 30219719
TI  - Tumor-associated carbonic anhydrase isoform IX and XII inhibitory properties of
      certain isatin-bearing sulfonamides endowed with in vitro antitumor activity
      towards colon cancer.
AB  - Three series of indolinone-based sulfonamides (3a-f, 6a-f and 9a-f) were in vitro
      evaluated as inhibitors of the tumor-associated carbonic anhydrase (CA, EC
      4.2.1.1) isoforms hCA IX and XII, using a stopped-flow CO2 hydrase assay. All the
      investigated sulfonamides displayed single- or double-digit nanomolar inhibitory
      activities towards both hCA IX (KIs: 6.2-64.8 nM) and XII (KIs: 7.1-55.6 nM)
      isoforms. All sulfonamides (3a-f, 6a-f and 9a-f) were in vitro examined for their
      potential anticancer activity against colorectal cancer HCT-116 and breast cancer
      MCF-7 cell lines. Sulfonamide 9e was found to be the most potent counterpart
      against HCT-116 (IC50 = 3.67 +/- 0.33 uM). Sulfonamide 9e displayed good
      selectivity profile for inhibition of the tumor-associated isoforms (CAs IX &
      XII) over the off-target cytosolic CAs I and II. 9e was screened for cell cycle
      disturbance and apoptosis induction in HCT-116 cells. It was found to persuade
      cell cycle arrest at G2-M stage as well as alter the Sub-G1 phase. Also, 9e
      induced the intrinsic apoptotic mitochondrial pathway in HCT-116 cells via down
      regulation of the anti-apoptotic protein Bcl-2 level with concurrent boosting the
      pro-apoptotic Bax, caspase-9, caspase-3, cytochrome C and p53 levels.

PMID- 30219721
TI  - Progress on nanostructured electrochemical sensors and their recognition elements
      for detection of mycotoxins: A review.
AB  - Nanomaterial-embedded sensors have been developed and applied to monitor various
      targets. Mycotoxins are fungal secondary metabolites that can exert carcinogenic,
      mutagenic, teratogenic, immunotoxic, and estrogenic effects on humans and
      animals. Consequently, the need for the proper  regulation on foodstuff and feed
      materials has been recognized from times long past. This review provides an
      overview of recent developments in electrochemical sensors and biosensors
      employed for the detection of mycotoxins. Basic aspects of the toxicity of
      mycotoxins and the implications of their detection are comprehensively discussed.
      Furthermore, the development of different molecular recognition elements and
      nanomaterials required for the detection of mycotoxins (such as portable
      biosensing systems for point-of-care analysis) is described. The current
      capabilities, limitations, and future challenges in mycotoxin detection and
      analysis are also addressed.

PMID- 30219722
TI  - Electrically nanowired-enzymes for probe modification and sensor fabrication.
AB  - Enzymes are highly specific and selective due to their precise, intricate three
      dimensional catalytic- structure. Electron transfer in enzymes normally occurs
      through an active-metal centers or tunneling events that are highly insulated by
      the surrounding globular protein structure. In case of electrochemically active
      enzymes/proteins, the distance between the redox-active cofactor and the
      electrode surface plays key role during direct communication. Therefore, the long
      electron-tunneling distance can be overcome by introducing mobile redox mediators
      such as nanostructures specially nanowires which can diffuse into and out of the
      enzyme active site, ferrying reducing or oxidizing equivalents with them.
      Therefore, nanowire-conjugated enzymes have gained great interest in the
      development of biosensor devices and other electrocatalytic-biological
      applications. Herein we present a comprehensive review about the electrochemical
      enzyme-based sensor using nanowires. Over the past decade, nanowires were
      investigated as a versatile platform for various applications including sensors
      and biosensors because of their high aspect ratio and a high surface-to-volume
      ratio. This review aimed to summarize some of the recent developments in the
      enzyme based sensor research that have been achieved with various metallic and
      non-metallic one-dimensional nanostructure i.e. nanowires. Due to low or no
      toxicity and biocompatibility, enzymes conjugated with nanowires are still highly
      specific, sensitive and biologically active. This review demonstrates the
      potential usability of nanowired-enzymes for the bioanalytical applications. The
      review includes various types of nanowires, mode of the enzyme integration or
      immobilization methodologies, probe modification, biosensor fabrication and real
      or spiked sample testing. Biosensor parameters such as linear range and
      sensitivity, selectivity and detection limit of reported sensors were also
      considered herein. We also introduce some of the new nanowire materials which
      have not yet been used for biosensing or biosensor application. The limitations,
      challenges and prospects for the use of nanowired-enzymes in electrochemical and
      other real-time sensing systems as well as fabrication technologies are also
      discussed in this review.

PMID- 30219720
TI  - Vitamin D status after colorectal cancer diagnosis and patient survival according
      to immune response to tumour.
AB  - BACKGROUND: High-level plasma 25-hydroxyvitamin D [25(OH)D] has been associated
      with lower colorectal cancer incidence and mortality. Considering evidence
      indicating immunomodulatory effects of vitamin D, we hypothesised that survival
      benefits from high systemic vitamin D level might be stronger for colorectal
      carcinoma with lower immune response to tumour. METHODS: Using 869 colon and
      rectal cancer cases within the Nurses' Health Study and Health Professionals
      Follow-up Study, we assessed the prognostic association of postdiagnosis 25(OH)D
      score [derived from diet and lifestyle variables to predict plasma 25(OH)D level]
      in strata of levels of histopathologic lymphocytic reaction. The Cox proportional
      hazards regression model was adjusted for potential confounders, including
      microsatellite instability, CpG island methylator phenotype, LINE-1 methylation,
      PTGS2 (cyclooxygenase-2) expression and KRAS, BRAF and PIK3CA mutations. RESULTS:
      The association of postdiagnosis 25(OH)D score with colorectal cancer-specific
      mortality differed by levels of peritumoural lymphocytic reaction (pinteraction =
      0.001). Multivariable-adjusted mortality hazard ratios for a quintile-unit
      increase of 25(OH)D score were 0.69 [95% confidence interval (CI), 0.54-0.89] in
      cases with negative/low peritumoural lymphocytic reaction, 1.08 (95% CI, 0.93
      1.26) in cases with intermediate peritumoural reaction and 1.25 (95% CI, 0.75
      2.09) in cases with high peritumoural reaction. The survival association of the
      25(OH)D score did not significantly differ by Crohn's-like lymphoid reaction,
      intratumoural periglandular reaction or tumour-infiltrating lymphocytes.
      CONCLUSIONS: The association between the 25(OH)D score and colorectal cancer
      survival is stronger for carcinomas with lower peritumoural lymphocytic reaction.
      Our results suggesting interactive effects of vitamin D and immune response may
      contribute to personalised dietary and lifestyle intervention strategies.

PMID- 30219723
TI  - Silver nanoparticles decorated and tetraphenylethene probe doped silica
      nanoparticles: A colorimetric and fluorometric sensor for sensitive and selective
      detection and intracellular imaging of hydrogen peroxide.
AB  - In this work, we report a novel sensor for colorimetric and fluorometric H2O2
      sensing which is based on silver nanoparticles decorated and tetraphenylethene
      probe doped silica nanoparticles (Ag@TPE-SiO2 NPs). A positively charged
      tetraphenylethene (TPE) probe is doped into silica nanoparticles, and the
      nanoparticles exhibit strong fluorescence emission due to aggregation-induced
      emission (AIE) of the TPE probe. Ag nanoparticles (AgNPs) are prepared in situ on
      the surface of the silica nanoparticles. AgNPs serve as a nanoquencher which can
      quench the AIE emission of the TPE-SiO2 NPs efficiently. However, AgNPs can be
      oxidized to Ag+ by H2O2, which leads to fluorescence recovery and color fading of
      the Ag@TPE-SiO2 NPs. The dual-readout strategy allows sensitive analysis of H2O2.
      The detection limit of the fluorometric and colorimetric assay is 0.28 and 2.1
      MUM, respectively. And the nanosensor also shows good selectivity. In addition,
      analysis of H2O2 in human serum and intracellular imaging of H2O2 are both
      demonstrated. With the good analytical properties of merit, the proposed
      nanoprobe has a promising potential for H2O2 related bioanalysis and biomedical
      applications.

PMID- 30219724
TI  - Biofunctionalized two-dimensional Ti3C2 MXenes for ultrasensitive detection of
      cancer biomarker.
AB  - In this work, ultrathin Ti3C2-MXene nanosheets were synthesized by minimally
      intensive layer delamination methods, and uniformly functionalized with
      aminosilane (f-Ti3C2-MXene) to provide a covalent binding for the immobilized bio
      receptor (anti-CEA) for label free, ultrasensitive detection of cancer biomarker
      (carcinoembryonic antigen, CEA). The effect of different redox probes on the
      electrochemical behavior of f-Ti3C2-MXene was investigated and found that
      hexaammineruthenium ([Ru(NH3)6]3+) is the preferable redox probe for biosensing.
      The fabricated biofunctionalized Ti3C2-MXene exhibits a linear detection range of
      0.0001-2000 ng mL-1 with sensitivity of 37.9 uA ng-1 mL cm-2 per decade. The
      wider linear detection range of our f-Ti3C2-MXene is not only higher than
      previously reported pristine 2D nanomaterials, but is even comparable to other
      hybrid 2D nanomaterials. We believe that this work opens a new window for
      development of MXene-based highly sensitive DNA, aptamer, enzyme, antibody, and
      cell based biosensors, and could be further used in drug delivery application.

PMID- 30219725
TI  - N-(aminobutyl)-N-(ethylisoluminol) functionalized Fe-based metal-organic
      frameworks with intrinsic mimic peroxidase activity for sensitive
      electrochemiluminescence mucin1 determination.
AB  - Herein, N-(4-aminobutyl)-N-(ethylisoluminol) functionalized Fe-based metal
      organic frameworks (ABEI/MIL-101(Fe)) with intrinsic mimic peroxidase activity
      was synthesized and utilized as highly efficient ECL indicator to construct
      sensitive immunosensor for mucin1 (MUC1) detection. Firstly, compared with the
      traditional method for ABEI immobilization, the proposed strategy could
      successfully achieve the highly efficient ABEI immobilization as ABEI coupled 2
      aminoterephhalic acid was used as organic bridge ligand. Moreover, the ABEI/MIL
      101(Fe) containing the same luminescent group as luminol could emit strong light
      when using hydrogen peroxide (H2O2) as a co-reactant. It is worth noting that the
      ECL signal of ABEI/MIL-101(Fe) could be greatly heightened due to the intrinsic
      mimic peroxidase activity of ABEI/MIL-101(Fe) that could accelerate the
      decomposition of H2O2 and produce considerable numbers of reactive oxygen
      radicals to participate in the ECL reaction of ABEI. The fabricated ECL
      immunosensor displayed a low detection limit of 1.6 fg mL-1 for MUC1, indicating
      that the synthesized ABEI/MIL-101(Fe) with intrinsic mimic peroxidase activity
      may be applied to realize ultrasensitive detection of other biomarkers in early
      diagnosis.

PMID- 30219726
TI  - The consumer-citizen duality: Ten reasons why citizens prefer safety and drivers
      desire speed.
AB  - Cost-benefit analyses for transportation projects usually value impacts on safety
      and travel time through experiments in which consumers of mobility ('drivers')
      choose between routes which differ in safety and travel time. This approach has
      been criticized for failing to consider that private choices may not fully
      reflect citizens' preferences over public goods and means, a concept known as the
      consumer-citizen duality. Recent empirical evidence has established that
      individuals do indeed assign comparatively more value to safety in their role as
      citizens than in their role as drivers. Our study aims to provide explanations
      for this finding by presenting four stated choice experiments in which
      respondents were asked to make choices, both as citizens and as drivers, between
      routes that differed in travel time and safety. Subsequently, respondents were
      asked to provide reasons for their choices. We identify five cognitive and five
      normative explanations. The cognitive explanations suggest that individuals make
      diverging choices because their perceptions of accident risk differ between the
      two roles. Drivers will assign a relatively low value to mitigating accident risk
      because they believe that: (1) such risks are trivial on an individual level; (2)
      their personal risk is lower than the average risk; (3) their personal risk is
      controllable; (4) they would not be able to distinguish relative safety levels in
      real life; and (5) their choices for others are more risk-averse than choices for
      themselves and, unlike citizens, they are not explicitly evaluating risky choices
      for others. The normative explanations involve that individuals believe that the
      government should assign more value to safety compared to individual drivers
      because: (6) as citizen they are more prone to base their choices on social norms
      which prescribe risk-averse behaviour in this context; (7) governments have a
      duty of care concerning the safety of the transportation network; (8) drivers
      have a relatively high degree of responsibility to reduce their own travel times;
      (9) governments should account for drivers' tendencies to choose faster routes by
      building safer ones; and (10) governments should ensure the safety of the road
      network because this allows drivers to choose the fastest route without being
      concerned about the impact of their route choice on accident risk.

PMID- 30219727
TI  - Regarding platelets and ductus: Is it platelet function rather than number that
      matters for ductal closure?

PMID- 30219728
TI  - Higher Dispositional Optimism Predicts Lower Pain Reduction During Conditioned
      Pain Modulation.
AB  - Optimism is associated with lower pain sensitivity, positive adjustment to
      chronic pain, and greater reduction of pain thresholds in a conditioned pain
      modulation (CPM) paradigm. We hypothesized that participants with higher levels
      of optimism would experience greater inhibition of suprathreshold pain during
      CPM. Seventy-seven healthy adults completed a test of optimism, the Life
      Orientation Test-Revised, as well as measures of depression, pain
      catastrophizing, and neuroticism. Participants also underwent psychophysical
      tests of heat pain tolerance, heat pain threshold, and CPM. CPM magnitude was
      calculated as the change in heat pain ratings when applied alone and
      simultaneously with painful pressure. Greater optimism was significantly
      correlated with reduced CPM magnitude (P = .013). Regression analysis was
      performed using optimism as a predictor of CPM magnitude while controlling for
      pain catastrophizing, neuroticism, depression, and age. The overall model was
      significant (P = .003). Significant positive coefficients were found for
      depression (P = .014) and optimism (P < .001) scores. These results suggest that
      greater optimism predicts less inhibition of suprathreshold pain, the opposite of
      our hypothesis. This unexpected finding may be due to factors such as perceived
      stress and coping differences, and suggests that modulation of threshold-level
      and suprathreshold pain involves different underlying mechanisms. PERSPECTIVE:
      This article reports that greater optimism predicts less inhibition of
      suprathreshold pain, in contrast with previous work showing that optimism
      correlates positively with pain threshold reductions. These findings suggest that
      the association between optimism and the function of endogenous pain modulatory
      systems is complex and differs for threshold-level and suprathreshold pain.

PMID- 30219729
TI  - Design and Reporting Characteristics of Clinical Trials of Select Chronic and
      Recurrent Pediatric Pain Conditions: An Analgesic, Anesthetic, and Addiction
      Clinical Trial Translations, Innovations, Opportunities, and Networks Systematic
      Review.
AB  - Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent
      pain in pediatric populations compared with adult populations; thus, data to
      support treatment efficacy in children are limited. This article evaluates the
      design features and reporting practices of RCTs for chronic and recurrent pain
      that are likely unique to, or particularly important in, a pediatric population
      to promote improvements in the evidence base for pediatric pain treatments. Areas
      covered include outcome measure selection and reporting and reporting of adverse
      events and challenges to recruitment and retention. A search of PubMed and EMBASE
      identified primary publications describing RCTs of treatments for select chronic
      and recurrent pain conditions in children or adolescents published between 2000
      and 2017. Only 49% of articles identified a primary outcome measure. The primary
      outcome measure assessed pain intensity in 38% of the trials, specifically
      measure by verbal rating scale (13%), faces pain scale (11%), visual analogue
      scale (9%), or numeric rating scale (5%). All of the CONSORT harms reporting
      recommendations were fulfilled by <50% of the articles. Discussions of
      recruitment challenges occurred in 64% of articles that enrolled <90% of their
      target sample. However, discussions regarding retention challenges only occurred
      in 14% of trials in which withdrawal rates were >10%. The goal of this article is
      to promote comprehensive reporting of pediatric pain RCTs to improve the design
      of future trials, facilitate conduction of systematic reviews and meta-analyses,
      and better inform clinical practice. PERSPECTIVE: This review of chronic and
      recurrent pediatric pain trials demonstrates inadequacies in the reporting
      quality of key features specifically important to pediatric populations. It
      provides recommendations that address these shortcomings to promote continued
      efforts toward improving the quality of the design and publication of future
      pediatric clinical pain trials.

PMID- 30219730
TI  - A Novel Finger Illusion Reveals Reduced Weighting of Bimanual Hand Cortical
      Representations in People With Complex Regional Pain Syndrome.
AB  - Complex regional pain syndrome (CRPS) is associated with deficits in sensorimotor
      control. Herein we have used a novel finger illusion to investigate whether CRPS
      is associated with reduced weighting of bimanual hand representations. The
      illusion normally induces a compelling feeling that the hands are close together
      when in fact they are 12 cm apart. People with CRPS and age, gender, and dominant
      hand-matched controls tested the illusion in the midline then on either side of
      the midline. The illusion had 2 variants; the passive pincer-grip position,
      without contact (no grasp condition) and with contact (grasp condition) of the
      artificial finger. The primary outcome was the perceived vertical distance
      between the index fingers. Twenty people with CRPS and 20 controls participated
      (mean age 44.4 +/- 11.7 years). During the no grasp condition, participants with
      CRPS perceived the vertical distance significantly closer to the actual 12 cm
      (mean 8.0 cm, 95% confidence interval 6.5-9.5 cm), than controls did (mean 6.4
      cm, 95% confidence interval 5.5-7.2 cm]). That is, the illusion was weaker in
      people with CRPS than in controls during no grasp. There was no such difference
      during grasp; that is, both groups showed the predicted illusion response. There
      was no effect of hand placement relative to midline or relative to the opposite
      hand. We conclude that people with unilateral CRPS have lower weighting of
      bimanual hand representation than controls have, independent of hand location.
      However, adding additional cutaneous input returns those with CRPS to the
      expected performance. We suggest the results have clear clinical and research
      implications. PERSPECTIVE: An abnormal weighting of bilateral hand representation
      may reflect a vulnerability for chronic CRPS, an adaptation to the disease,
      and/or a potential therapeutic target. That addition of cutaneous input
      immediately normalizes the problem points to the possible role of bimanual tasks
      in prevention or rehabilitation.

PMID- 30219731
TI  - Metformin attenuates diabetes-induced tau hyperphosphorylation in vitro and in
      vivo by enhancing autophagic clearance.
AB  - Diabetes mellitus (DM) can increase the risk of Alzheimer's disease (AD) in
      patients. However, no effective approaches are available to prevent its
      progression and development. Recently, autophagy dysfunction was identified to be
      involved in the pathogenesis of neurodegenerative diseases. This study was
      designed to investigate the effect of metformin on hyperphosphorylated tau
      proteins in diabetic encephalopathy (DE) by regulating autophagy clearance. db/db
      mice were randomly divided into four groups, db/+ mice were used as control
      group. Twelve-week old male db/db mice received consecutive intraperitoneal
      injection of 200 mg/kg/d metformin or (and) 10 mg/kg/d chloroquine for eight
      weeks. Morris water maze (MWM) tests were performed to test cognitive functions
      before the mice were euthanized. Metformin attenuated cognitive impairment in
      db/db mice, reduced hyperphosphorylated tau proteins, restored the impaired
      autophagy in diabetic mice, all of which were reversed by inhibiting of autophagy
      activity. In high glucose-cultured HT22 cells, metformin increased autophagy in a
      dose-dependent manner. Besides, metformin enhanced autophagy activity in an AMPK
      dependent manner. These data show that metformin may reduce tauopathy and improve
      cognitive impairment in db/db mice by modulating autophagy through the AMPK
      dependent pathway. These findings highlight metformin as a new therapeutic
      strategy for the treatment of DE.

PMID- 30219732
TI  - Long-term social isolation inhibits autophagy activation, induces postsynaptic
      dysfunctions and impairs spatial memory.
AB  - Social isolation in adolescence leads to lasting deficits in hippocampal
      dependent tasks. The reported effects of isolation on learning and memory in the
      Morris water maze and synaptic-related proteins have been inconsistent. Moreover,
      the autophagy level and its effect on cognition in the isolation model are also
      not clear. In the present study, we did an extended isolation period up to six
      months to establish a stable and appropriate isolation model to investigate the
      cognitive changes associated with it. The mTOR inhibitor rapamycin was
      systemically administered to mice to determine the roles of autophagy activation
      on cognitive changes. We discovered that long-term post-weaning social isolation
      (L-PWSI) produced marked deficits in spatial learning and memory and inhibited
      CA1 long-term potentiation (LTP), but paired-pulse facilitation (PPF) and
      input/output (I/O) curve were unaffected. The results further showed that the L
      PWSI significantly decreased the protein expression levels of PSD-95, GluA1, NR1
      and NR2B in the hippocampus, and no significant changes in the extracellular
      release of glutamate and the protein expression levels of synaptophysin, synapsin
      I, GAP-43, NR2A and GABAA. Moreover, we found that L-PWSI increased the protein
      expression of p-AKT/AKT, p-mTOR/mTOR and p62, whereas the protein levels of LC3B
      and Beclin1 were decreased indicating an inhibition in autophagy activity.
      Intraperitoneal injection of rapamycin significantly potentiated fEPSP slope and
      cognition-related proteins expression in the L-PWSI mice. These results therefore
      suggest that L-PWSI induces postsynaptic dysfunction by disrupting the
      interaction between AMPAR, NMDAR and PSD-95, and inhibit the autophagy activity
      which led to impaired spatial memory and cognitive function.

PMID- 30219733
TI  - A smart and operator independent system to delineate tumours in Positron Emission
      Tomography scans.
AB  - Positron Emission Tomography (PET) imaging has an enormous potential to improve
      radiation therapy treatment planning offering complementary functional
      information with respect to other anatomical imaging approaches. The aim of this
      study is to develop an operator independent, reliable, and clinically feasible
      system for biological tumour volume delineation from PET images. Under this
      design hypothesis, we combine several known approaches in an original way to
      deploy a system with a high level of automation. The proposed system
      automatically identifies the optimal region of interest around the tumour and
      performs a slice-by-slice marching local active contour segmentation. It
      automatically stops when a "cancer-free" slice is identified. User intervention
      is limited at drawing an initial rough contour around the cancer region. By
      design, the algorithm performs the segmentation minimizing any dependence from
      the initial input, so that the final result is extremely repeatable. To assess
      the performances under different conditions, our system is evaluated on a dataset
      comprising five synthetic experiments and fifty oncological lesions located in
      different anatomical regions (i.e. lung, head and neck, and brain) using PET
      studies with 18F-fluoro-2-deoxy-d-glucose and 11C-labeled Methionine radio
      tracers. Results on synthetic lesions demonstrate enhanced performances when
      compared against the most common PET segmentation methods. In clinical cases, the
      proposed system produces accurate segmentations (average dice similarity
      coefficient: 85.36 +/- 2.94%, 85.98 +/- 3.40%, 88.02 +/- 2.75% in the lung, head
      and neck, and brain district, respectively) with high agreement with the gold
      standard (determination coefficient R2 = 0.98). We believe that the proposed
      system could be efficiently used in the everyday clinical routine as a medical
      decision tool, and to provide the clinicians with additional information, derived
      from PET, which can be of use in radiation therapy, treatment, and planning.

PMID- 30219734
TI  - The effect of cut-off frequency when high-pass filtering equine sEMG signals
      during locomotion.
AB  - High-pass filtering (HPF) is a fundamental signal processing method for the
      attenuation of low-frequency noise contamination, namely baseline noise and
      movement artefact noise, in human surface electromyography (sEMG) research.
      Despite this, HPF is largely overlooked in equine sEMG research, with many
      studies not applying, or failing to describe, the application of HPF. An optimal
      HPF cut-off frequency maximally attenuates noise while minimally affecting sEMG
      signal power, but this has not been investigated for equine sEMG signals. The aim
      of this study was to determine the optimal cut-off frequency for attenuation of
      low-frequency noise in sEMG signals from the Triceps Brachii and Biceps Femoris
      of 20 horses during trot and canter. sEMG signals were HPF with cut-off
      frequencies ranging from 0 to 80 Hz and were subjected to power spectral analysis
      and enveloped using RMS to calculate spectral peaks, indicative of motion
      artefact, and signal loss, respectively. Processed signals consistently revealed
      a low-frequency peak between 0 and 20 Hz, which was associated with motion
      artefact. Across all muscles and gaits, a 30-40 Hz cut-off fully attenuated the
      low-frequency peak with the least amount of signal loss and was therefore
      considered optimal for attenuating low-frequency noise from the sEMG signals
      explored in this study.

PMID- 30219735
TI  - Lifetime risk of cardiometabolic mortality according to vitamin D status of
      middle and older-aged adults: NHANES III mortality follow-up.
AB  - The predictive value of total 25-hydroxyvitamin D (25(OH)D, a biomarker of
      vitamin D status) in relation to lifetime risk of cardiometabolic mortality is
      not known. The purpose of this study was to determine the association between
      standardized and annualized total 25(OH)D levels and lifetime risk for
      cardiometabolic mortality in middle- to older-aged adults. In this study, we
      followed up 7958 participants in the Third National Health and Nutrition
      Examination Survey from 1988 to 1994 (NHANES III) until the occurrence of
      cardiometabolic death or attainment of 95 years of age (median follow-up 17.9
      years, 1371 cardiometabolic-deaths). Lifetime risks were estimated according to
      recommended total 25(OH)D cutoffs by national guidelines, and a combination of
      total 25(OH)D status and traditional risk factor burden. We also explored
      variation in lifetime risk estimates by levels of body mass index (BMI). The
      results of this study showed that annualized total 25(OH)D <30 nmol/L was
      associated with high lifetime risk of cardiometabolic mortality (40%). Lifetime
      risks of cardiometabolic mortality were similar for annualized levels between 30
      < 50 nmol/L, 50-< 75 nmol/L and >=75 nmol/L (31-33%). Lifetime risk was highest
      among participants with annualized total 25(OH)D <30 nmol/L and >=2 major
      traditional risk factors (45%), whereas lifetime risk was lowest among
      participants with annualized 25(OH)D >=30 nmol/L and low-intermediate risk
      factors (28%). Lifetime risk estimates were similar across BMI categories. In
      conclusion, a single measurement of vitamin D deficiency (annualized levels <30
      nmol/L) in middle- to older-aged adults is a strong predictor of high lifetime
      risk for cardiometabolic mortality, particularly among those with high burden of
      traditional risk factors.

PMID- 30219736
TI  - Parental drinking as context for parental socialization of adolescent alcohol
      use.
AB  - INTRODUCTION: While alcohol-specific parenting practices have demonstrated unique
      effects on adolescent substance use, their efficacy in the context of parental
      drinking levels has not been studied. This study assessed the influence of three
      alcohol-specific parenting practices (rules, punishment, communication) on
      adolescent alcohol use, and the degree to which those associations varied by
      parents' own drinking. METHODS: We conducted logistic regression analyses among
      US adolescents (N = 1023; 52% female; 12% Hispanic; 76% Caucasian, 5% Black, 8%
      mixed race, 11% other race/ethnicity; mean age at enrollment = 12.2 years) to
      examine the relationship between alcohol-specific parenting practices and the
      odds of ever having experienced two drinking milestones, having a full drink of
      alcohol and a heavy drinking episode, and whether parental drinking levels
      moderated those associations. RESULTS: Strict rules for drinking, higher levels
      of cautionary communication messages, and punishment for drinking were associated
      with lower odds of alcohol use. Witnessing parent drinking increased the risk for
      both alcohol outcomes. Furthermore, parental drinking modified the influence of
      parental cautionary messages on alcohol use such that the effect was particularly
      salient for those youth who witnessed and whose parents reported higher levels of
      alcohol use. CONCLUSIONS: Family-based preventive interventions should include
      skills training in alcohol-specific parenting practices with emphasis on reducing
      parental alcohol use particularly when children are present.

PMID- 30219737
TI  - Case-control comparison brain lesion segmentation for early infarct detection.
AB  - Computed Tomography (CT) images are widely used for the identification of
      abnormal brain tissues following infarct and hemorrhage of a stroke. The
      treatment of this medical condition mainly depends on doctors' experience. While
      manual lesion delineation by medical doctors is currently considered as the
      standard approach, it is time-consuming and dependent on each doctor's expertise
      and experience. In this study, a case-control comparison brain lesion
      segmentation (CCBLS) method is proposed to segment the region pertaining to brain
      injury by comparing the voxel intensity of CT images between control subjects and
      stroke patients. The method is able to segment the brain lesion from the stacked
      CT images automatically without prior knowledge of the location or the presence
      of the lesion. The aim is to reduce medical doctors' burden and assist them in
      making an accurate diagnosis. A case study with 300 sets of CT images from
      control subjects and stroke patients is conducted. Comparing with other existing
      methods, the outcome ascertains the effectiveness of the proposed method in
      detecting brain infarct of stroke patients.

PMID- 30219738
TI  - Preparation of surfaces of composite samples for tip based micro-analyses using
      ion beam milling.
AB  - Ion beam milling, as a method of surface design for tip analytical techniques,
      was explored. A sample of clay, embedded in a resin, was treated by the ion beam
      and allowed AFM (a typical tip technique) to be successfully applied. The method
      is suitable for advanced tip analyses based on AFM, like TERS or SNOM, and for
      samples that are not possible to prepare by standard mechanical methods. The
      approach can be useful for characterisation of the surfaces of many different
      types of materials in versatile applications such as catalysis, corrosion science
      or advanced material characterisation.

PMID- 30219739
TI  - Fast-FineCut: Grain boundary detection in microscopic images considering 3D
      information.
AB  - The inner structure of a material is called its microstructure. It stores the
      genesis of a material and determines all the physical and chemical properties.
      However, the microstructure is highly complex and numerous image defects such as
      vague or missing boundaries formed during sample preparation, which makes it
      difficult to extract the grain boundaries precisely. In this work, we address the
      task of grain boundary detection in microscopic image processing and develop a
      graph-cut based method called Fast-FineCut to solve the problem. Our algorithm
      makes two key contributions: (1) An improved approach that incorporates 3D
      information between slices as domain knowledge, which can detect the boundaries
      precisely, even for the vague and missing boundaries. (2) A local processing
      method based on overlap-tile strategy, which can not only solve the "chain
      scission" problem at the edge of images, but also economize on the consumption of
      computing resources. We conduct experiments on a stack of 296 slices of
      microscopic images of polycrystalline iron (1600 * 2800) and compare the
      performance against several state-of-the-art boundary detection methods. We
      conclude that Fast-FineCut can detect boundaries effectively and efficiently.

PMID- 30219742
TI  - The Vapnik-Chervonenkis dimension of graph and recursive neural networks.
AB  - The Vapnik-Chervonenkis dimension (VC-dim) characterizes the sample learning
      complexity of a classification model and it is often used as an indicator for the
      generalization capability of a learning method. The VC-dim has been studied on
      common feed-forward neural networks, but it has yet to be studied on Graph Neural
      Networks (GNNs) and Recursive Neural Networks (RecNNs). This paper provides upper
      bounds on the order of growth of the VC-dim of GNNs and RecNNs. GNNs and RecNNs
      are from a new class of neural network models which are capable of processing
      inputs that are given as graphs. A graph is a data structure that generalizes the
      representational power of vectors and sequences, via the ability to represent
      dependencies or relationships between feature vectors. It was shown previously
      that the ability of recurrent neural networks to process sequences increases the
      VC-dim when compared to the VC-dim of Neural Networks, which are limited to
      processing vectors. Since graphs are a more general form than sequences, the
      question arises how this will affect the VC-dimension of GNNs and RecNNs. A main
      finding in this paper is that the upper bounds on the VC-dim for GNNs and RecNNs
      are comparable to the upper bounds for recurrent neural networks. The result also
      suggests that the generalization capability of such models increases with the
      number of connected nodes.

PMID- 30219741
TI  - Magic angles and fibre stretch in arterial tissue: Insights from the linear
      theory.
AB  - This work is motivated by the current widespread interest in modelling the
      mechanical response of arterial tissue. A widely used approach within the context
      of anisotropic nonlinear elasticity is to use an orthotropic incompressible
      hyperelasticity model which, in general, involves a strain-energy density that
      depends on seven independent invariants. The complexity of such an approach in
      its full generality is daunting and so a number of simplifications have been
      introduced in the literature to facilitate analytical tractability. An extremely
      popular model of this type is where the strain energy involves only three
      invariants. While such models and their generalisations have been remarkably
      successful in capturing the main features of the mechanical response of arterial
      tissue, it is generally acknowledged that such simplified models must also have
      some drawbacks. In particular, it is intuitively clear that the correlation of
      such models with experiment will suffer limitations due to the restricted number
      of invariants considered. Our purpose here is to use the linearised theory for
      infinitesimal deformations to provide some guidelines for the development of a
      more robust nonlinear theory. The linearised theory for incompressible
      orthotropic materials is developed and involves six independent elastic
      constants. The general stress-strain law is inverted to provide an expression for
      the fibre stretch in terms of the stress. We examine the linearised response for
      simple tension in two mutually perpendicular directions corresponding to the
      axial and circumferential directions in the artery, obtaining an explicit
      expression for the fibre stretch in terms of the applied tension, fibre angle and
      linear elastic constants. The focus is then on determining the range of fibre
      orientation angles that ensure that the fibres are in tension in these simple
      tension tests. It is shown that the fibre stretch is positive for both simple
      tension tests if and only if the fibre angle is restricted to lie between two
      special angles called generalised magic angles. For the special case where the
      strain-energy function for the nonlinear model depends only on the three
      invariants I1,I4,I6, it is shown that the corresponding linearised model, called
      the standard linear model (SLM), depends on three elastic constants and the fibre
      stretch is positive only in the small range of fibre angles between the classic
      magic angles 35.26 degrees  and 54.74 degrees . However, when the two additional
      invariants I5,I7 are included in the nonlinear strain energy so that the
      corresponding linear model involves four elastic constants, it is shown that the
      domain of fibre angle for which the stretch is positive is much larger and that
      the fibre stretch is monotonic with respect to the fibre angle in this range.

PMID- 30219740
TI  - Agricultural adjuvants may impair leaf transpiration and photosynthetic activity.
AB  - Adjuvants such as surfactants are commonly incorporated into agrochemical
      formulations to enhance the biological efficiency of foliar sprays by improving
      the wetting behavior of the spray and/or the penetration of the active
      ingredients into the leaf tissues. Penetration accelerating adjuvants are known
      to increase the cuticular permeability and may alter the cuticular barrier to
      water loss. However, none or very little emphasis has been given to the impacts
      of adjuvants on crop water balance or drought tolerance, a very important factor
      affecting crop performance under water scarcity. Two model crops with strongly
      varying leaf traits, kohlrabi (Brassica oleracea) and apple (Malus domestica)
      seedlings were grown in controlled environments. Three adjuvants with varying
      solubility in the cuticle, i.e. octanol-water partition coefficients (logKow)
      were selected: rapeseed methyl ester (RME) and the surfactants alkyl
      polyglycoside (APG) and polyoxyethylated tallow amine (POEA). The higher the
      logKow of the adjuvant, the stronger was the increase of minimum epidermal
      conductance (gmin, an essential parameter describing plant drought tolerance).
      However, such effects depended on the physio-chemical properties of the leaf
      surface. In comparison to kohlrabi, the adjuvant effects on gmin of apple leaves
      were relatively weak. The increase of gmin was associated with a decrease in
      contact angle and with an alteration of the wax microstructure. Furthermore, POEA
      affected photochemical efficiency of kohlrabi leaves. Some adjuvants could have a
      temporal influence on transpirational water loss and gmin. At repeated
      applications, they might alter the effective water use and possibly reduce
      drought tolerance of some horticultural crops.

PMID- 30219743
TI  - NMOSD with anti-MOG antibodies following anti-TNFalpha therapy: A case report.
AB  - Tumor necrosis factor alpha (TNFalpha) inhibitors are highly effective and a
      therapeutic choice for several inflammatory diseases. Their broad and long-term
      use is associated with a growing number of paradoxical autoimmune events
      including demyelinating lesions of the central nervous system (CNS). We report
      and discuss a case of neuromyelitis optica spectrum disorder (NMOSD) with
      positive myelin oligodendrocyte glycoprotein antibodies (MOG-IgG1) following anti
      TNFalpha therapy for a pustular psoriasis.

PMID- 30219744
TI  - Promising effect of rapamycin on multiple sclerosis.
AB  - The routine therapies for relapsing-remitting multiple sclerosis (RRMS) are
      common disease-modifying medications, yet are not effective in all patients. The
      aim of the present clinical trial was to evaluate the therapeutic effects of
      rapamycin on the clinical and radiological aspects, regulatory T cells
      proliferation and FOXP3 and GARP gene expression in the patients with RRMS. In
      this study, eight patients with RRMS were chosen and included in the trial.
      Patients received rapamycin (Rapacan, Biocon, India) for six months. Magnetic
      resonance imaging (MRI) of the patients' brain was taken before and after the
      therapy. Patients' expanded disability status scale (EDSS), and FoxP3 and GARP
      gene expression, and Treg cell proliferation were also been evaluated. All the
      patients had some degrees of significant reduction in mean plaque area size (P =
      0.012, Z = -2.520), and minimum and maximum size of the plaques (P = 0.012, Z = 
      2.521). EDSS of 50% of patients was decreased after the treatment, yet it was not
      significant (P = 0.059, Z = -1.89). The expression rate of FOXP3 (P = 0.003) and
      GARP genes in Tregs increased after the therapy. We found a promising response to
      rapamycin among our cases with minor side effects and it may be considered as a
      therapeutic option of this disease.

PMID- 30219745
TI  - What are reaction time indices of automatic imitation measuring?
AB  - Humans unintentionally copy other people's gestures, postures and speech
      patterns. This behaviour has been termed 'automatic imitation', and is thought to
      play a crucial role in the development of social relationships by building
      affiliation and rapport between interaction partners. The current paper
      critically evaluates reaction time measures of automatic imitation and
      demonstrates that it is currently unclear what reaction time indices measure, due
      to a lack of research assessing dimensions of validity and domain-specificity.
      Based on this assessment of the literature, three suggestions are made for future
      research. First, studies that assess the validity of reaction time paradigms as
      an index of automatic imitation are required. That is, the extent that processes
      involved in reaction time measures of automatic imitation also operate in real
      world copying behaviours needs firmly establishing. Second, the extent that
      component processes of automatic imitation rely on domain-specific, domain
      general or a combination of both types of cognitive system needs establishing.
      Moreover, theories of imitation that move beyond neat divisions between domain
      specific and domain-general systems should be prioritised. Third, a case is made
      for why methodological rigour requires far more emphasis in order to support the
      development of a cumulative science of automatic imitation. In sum, by providing
      a critical review of the current literature, as well as suggesting new directions
      for research questions, theories and methods, this paper aims to stimulate
      discussion regarding optimal approaches to studying automatic imitation.
      Moreover, the analysis and recommendations presented here generalise to other
      domains of social cognition, such as gaze perception and perspective taking,
      which also rely on similar reaction time paradigms.

PMID- 30219746
TI  - The role of task difficulty in theoretical accounts of mind wandering.
AB  - Recent research has indicated that reducing the difficulty of a task by
      increasing the predictability of critical stimuli produces increases in
      intentional mind wandering, but, contrary to theoretical expectations, decreases
      in unintentional mind wandering. Here, we sought to determine whether reducing
      task difficulty by reducing working-memory load would yield similar results.
      Participants completed an easy (Choice Response Time; CRT) task and a relatively
      difficult (Working Memory; WM) task, and intermittently responded to thought
      probes asking about intentional and unintentional mind wandering. As in prior
      studies, we found higher rates of intentional mind wandering during the easy
      compared to the more difficult task. However, we also found more unintentional
      mind wandering during the difficult compared to the easy task. We discuss these
      results in the context of theoretical accounts of mind wandering.

PMID- 30219747
TI  - Genetic diversity of Hepatitis C Virus in Pakistan using Next Generation
      Sequencing.
AB  - BACKGROUND: In Pakistan, HCV disease is considered a major public health issue
      with about 10-17 million people suffering with this infection and rate is
      increasing every day without any hindrance. The currently available
      Pyrosequencing approach used to analyze complex viral genomes as it can determine
      minor variants. It is crucial to understand viral evolution and quasispecies
      diversity in complex viral strains. OBJECTIVES: To assess genetic diversity in
      patients with HCV using Next Generation Sequencing (NGS) and compare nucleotide
      diversity of genotype 3a with respect to other genotypes. STUDY DESIGN: Intra
      host viral diversity of HCV was determined using NGS from 13 chronically HCV
      infected individuals. NGS of three different regions (E2 (HVR1), NS3 and NS5B) of
      HCV-3a allowed for a comprehensive analysis of the viral population. RESULT:
      Phylogenetic analysis of different HCV genes revealed great variability within
      the Pakistani population. The average nucleotide diversity for HVR1, NS3 and NS5B
      was 0.029, 0.011 and 0.010 respectively. CONCLUSION: Our findings clearly
      indicate that patient-2 greater quasispecies heterogeneity than other patients of
      same genotype-3a using phylogenetic and one step network analyses. Initially
      phylogenetic analysis of these three genes showed that genotype 3a samples have
      greater genetic diversity. However, no significant difference was determined when
      nucleotide variability of genotype 3a compared with other genotypes (1a, 1b, 2a &
      4a).

PMID- 30219748
TI  - Gender and the language of pain in chronic and terminal illness: A corpus-based
      discourse analysis of patients' narratives.
AB  - Drawing on the notion of gender as a socially constructed category performed
      inter alia through language, this study examines the ways in which women and man
      use language to do person-in-pain in real-life interactions about chronic and
      terminal illness. It is based on a secondary analysis of a large corpus of health
      and illness narratives collected by the Health Experiences Research Group at the
      University of Oxford and published by the DIPEx charity. Sixteen chronic and
      terminal conditions were identified in which men and women talked about physical
      pain and their narratives examined using the linguistic approach of a corpus
      assisted discourse analysis. Our study shows that there are significant
      quantitative and qualitative differences in the ways in which women and men
      report pain pointing to the existence of distinctive feminine and masculine
      lexical repertoires of pain talk. While these repertoires conform to some of the
      dominant societal stereotypes surrounding masculinity and femininity, they also
      transgress those. Women refer to pain more frequently and have a wider lexical
      repertoire for pain reporting. They use more specific and factual references as
      well as cognitive and psychological words in their pain talk. In contrast, men
      tend to use fewer descriptors in general, most of which are highly emotive
      suggesting that they report pain when it becomes unbearable enduring it until
      this point. There is also a conspicuous absence of references to psychological
      processes in the male narratives and the focus is on pain killers. Understanding
      this nuanced role of gender in communicating pain can help health professionals
      respond effectively to people's talk about pain and develop more holistic
      practices in pain consultation, assessment and treatment leading potentially to
      the reduction of gender biases and inequalities in healthcare.

PMID- 30219749
TI  - Investigating inequities in hospital care among lesbian, gay, bisexual, and
      transgender (LGBT) individuals using social media.
AB  - RATIONALE: Persons who identify as lesbian, gay, bisexual, and transgender (LGBT)
      face health inequities due to unwarranted discrimination against their sexual
      orientation or identity. An important contributor to LGBT health disparities is
      the inequitable or substandard care that LGBT individuals receive from hospitals.
      OBJECTIVE: To investigate inequities in hospital care among LGBT patients using
      the popular social media platform Twitter. METHOD: This study examined a dataset
      of Twitter communications (tweets) collected from February 2015 to May 2017. The
      tweets mentioned Twitter handles for hospitals (i.e., usernames for hospitals)
      and LGBT related terms. The topics discussed were explored to develop an LGBT
      position index referring to whether the hospital appears supportive or not
      supportive of LGBT rights. Results for each hospital were then compared to the
      Healthcare Equality Index (HEI), an established index to evaluate equity of
      hospital care towards LGBT patients. RESULTS: In total, 1856 tweets mentioned
      LGBT terms representing 653 unique hospitals. Of these hospitals, 189 (28.9%)
      were identified as HEI leaders. Hospitals in the Northeast showed significantly
      greater support towards LGBT issues compared to hospitals in the Midwest.
      Hospitals deemed as HEI leaders had higher LGBT position scores compared to non
      HEI leaders (p = 0.042), when controlling for hospital size and location.
      CONCLUSIONS: This exploratory study describes a novel approach to monitoring LGBT
      hospital care. While these initial findings should be interpreted cautiously,
      they can potentially inform practices to improve equity of care and efforts to
      address health disparities among gender minority groups.

PMID- 30219750
TI  - Attitudes toward alcohol use during pregnancy among women recruited from alcohol
      serving venues in Cape Town, South Africa: A mixed-methods study.
AB  - BACKGROUND: The Western Cape Province of South Africa has one of the highest
      rates of fetal alcohol spectrum disorder (FASD) globally. Effective prevention of
      FASD requires understanding women's attitudes about alcohol use during pregnancy
      and whether these attitudes translate into behavior. OBJECTIVE: The goal of this
      mixed-methods study was to describe attitudes toward alcohol use during pregnancy
      and examine how these attitudes influence drinking behaviors during pregnancy.
      METHOD: Over a five month period, 200 women were recruited from alcohol-serving
      venues in a township in Cape Town; a sub-set of 23 also completed in-depth
      interviews. Potential gaps between attitudes and behavior were described, and
      logistic regression models examined predictors of harmful attitudes toward
      alcohol use during pregnancy. Interviews were reviewed and coded for emergent
      themes. RESULTS: Most women (n = 176) reported at least one pregnancy. Among
      these, the majority (83%) had positive preventive attitudes, but more than half
      of these still reported alcohol use during a previous pregnancy. The strongest
      predictors of harmful attitudes were a history of physical or sexual abuse and
      drinking during a previous pregnancy. Qualitative analysis revealed several
      themes that contributed to alcohol use during pregnancy: 1) having an unplanned
      pregnancy; 2) drinking because of stress or to cope with abuse/trauma; 3)
      reliance on the venue for support; 4) socialization; and 5) feelings of
      invincibility. CONCLUSIONS: The findings highlight an attitude-behavior gap and
      suggest that positive preventive attitudes are insufficient to elicit FASD
      preventive behavior. Interventions are needed that go beyond education to build
      intrinsic motivation and structural support to refrain from alcohol use during
      pregnancy.

PMID- 30219752
TI  - Bridging the gap in knowledge between dyspnoea scientists and clinicians.

PMID- 30219751
TI  - The European Respiratory Society: ensuring excellence through education best
      practice.

PMID- 30219753
TI  - Chronic breathlessness: time for Cinderella to go to the ball!

PMID- 30219754
TI  - Dissecting respiratory disease heterogeneity through the genetics of diffusing
      capacity.

PMID- 30219755
TI  - ERS Clinical Research Collaborations: underpinning research excellence.

PMID- 30219756
TI  - Public health for paediatricians:How can behavioural economics help to make
      paediatric practice more effective?
AB  - Understanding the principles of behavioural economics is important for
      paediatricians because behavioural economics offers ideas to help improve the
      quality of paediatric care. It can also be used to inform health
      interventions/policy at a population level. This paper summarises key behavioural
      economic concepts such as bounded rationality, bounded willpower and social
      influence, explaining how they can be used to shape healthy behaviours in
      children and adolescents. Case studies of interventions that have used
      behavioural economics principles (sometimes called 'nudge theory') are provided.

PMID- 30219757
TI  - Twelve-year-old boy presenting with recurrent abdominal pain and 25 urinary
      calculi.
AB  - : A 12-year-old boy, with intermittent abdominal pain from 3 years of age,
      presented with increased frequency of right lower quadrant pain (at least three
      episodes per week over the past six months) and pain during micturition affecting
      school attendance. His family history included referred urolithiasis. An
      abdominal ultrasound performed 1 year before our visit showed a small stone of 4
      mm in the right renal pelvis for which he did not receive any therapy. The
      patient brought 25 hard stones with irregular outline, 2-8 mm in diameter, of
      deep brown/grey colour that he claimed to have found in his underwear (figure 1).
      On examination, he looked well with normal vital signs and unremarkable
      cardiorespiratory and abdominal examinations. Plasma creatinine was 0.41 mg/dL
      (36.1 MUmol/L), urinalysis and urine tests were all normal (including 24 hour
      calcium, phosphorus, oxalate, citrate, uric acid and cystine). Repeat kidney and
      urinary tract ultrasound showed no evidence of calculi.edpract;archdischild-2018
      315073v1/F1F1F1Figure 1Twenty-five hard formations brought along by the patient
      from home. QUESTION 1: Which is the most likely diagnosis?Cystinuria.Dent
      disease.Idiopathic urolithiasis.Factitious disorder imposed on self.Familial
      hypomagnesemia with hypercalciuria and nephrocalcinosis. QUESTION 2: How would
      you confirm your diagnostic suspicion?Reassurance and clinical follow-up.Mass
      spectrometry of stones.CT urography.Increase oral fluid intake and administration
      of potassium citrate. QUESTION 3: How would you manage this
      condition?Administration of placebo.Psychological consultation.Observed 24 hour
      urine collection.All of the above. Answers can be found on page 2.

PMID- 30219758
TI  - Non-pharmacological approaches to infantile colic: white noise versus swinging.

PMID- 30219759
TI  - There is a lack of preventive care and treatment interventions for urinary
      incontinence in hospitalised adults.

PMID- 30219760
TI  - Professionals need to discuss more effectively the holistic needs of their
      patients regarding palliative care.

PMID- 30219761
TI  - Association of Medication Beliefs, Self-efficacy, and Adherence in a Diverse
      Cohort of Adults with Rheumatoid Arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) patients' adherence to disease-modifying
      antirheumatic drugs (DMARD) is often suboptimal. We examined associations among
      medication beliefs, self-efficacy, and adherence to medications in RA. METHODS:
      Data were from a longitudinal observational cohort of persons with RA. Subjects
      completed telephone interviews on self-reported adherence, self-efficacy,
      demographics, and the Beliefs about Medicines Questionnaire (BMQ), which assesses
      beliefs in necessity and beliefs about taking medication. Bivariate and
      multivariate logistic regression identified correlates of poor adherence to
      synthetic DMARD and prednisone as well as to biologic therapy, including
      medication concerns and necessity. RESULTS: There were 362 patients who reported
      taking a synthetic DMARD and/or prednisone. Of these, 14% and 21% reported poor
      adherence to oral DMARD or prednisone, and biologics, respectively. There were
      64% who reported concern about taking medicines, 81% about longterm effects, and
      47% about becoming too dependent on medicines. In multivariate analyses, the BMQ
      necessity score was independently associated with better adherence to oral DMARD
      or prednisone (adjusted OR 0.61, 95% CI 0.41-0.91), while self-efficacy was
      associated with greater odds of poor adherence to oral medications (adjusted OR
      1.23, 95% CI 1.01-1.59). Beliefs in medicines and self-efficacy were not
      associated with adherence to biologics. CONCLUSION: In a diverse cohort of
      patients with RA, stronger beliefs in the necessity of medication were associated
      with better adherence to oral DMARD or prednisone, while higher self-efficacy was
      associated with poor adherence. Providers can play important roles in eliciting
      patient beliefs about medications to improve adherence and ultimately health
      outcomes.

PMID- 30219762
TI  - Complement C5-blocking Agent in Refractory Dermatomyositis.

PMID- 30219763
TI  - Multiplex Polymerase Chain Reaction and Microcalorimetry in Synovial Fluid: Can
      Pathogen-based Detection Assays Improve the Diagnosis of Septic Arthritis?
AB  - OBJECTIVE: To prospectively evaluate automated multiplex PCR and isothermal
      microcalorimetry tests for rapid and accurate diagnosis of septic arthritis.
      METHODS: Patients with acute arthritis were prospectively included from October
      2014 to September 2015. In synovial fluid (SF), leukocyte count and differential,
      culture, PCR, and microcalorimetry were determined. Septic arthritis was
      diagnosed by positive SF culture or (1) local clinical signs and symptoms, (2)
      increased SF leukocyte count, and (3) exclusion of noninfectious causes of
      inflammatory arthropathy. The performance of individual tests was compared with
      McNemar's test. RESULTS: Among 57 patients, 22 (39%) were diagnosed with septic
      arthritis. SF culture grew a pathogen in 10 patients (46%), PCR was positive in 5
      (23%), and microcalorimetry in 10 (46%). Compared to SF culture, 49 concordant
      pairs were found for both methods (PCR and microcalorimetry; 86% agreement). In
      SF, PCR failed to detect Staphylococcus aureus (2 patients), Streptococcus
      pneumoniae (1 patient), Streptococcus dysgalactiae (1 patient), and Clostridium
      clostridioforme (1 patient). Microcalorimetry failed to detect S. dysgalactiae (1
      patient), Streptococcus agalactiae (1 patient), and C. clostridioforme (1
      patient). No statistical differences between the performance of SF culture, and
      PCR and microcalorimetry, respectively, were found. The processing time for PCR
      was 5 h and for microcalorimetry a median of 8.8 h (range, 2.3-64 h), whereas
      cultures required a median of 4.5 days (range, 3-14 days). CONCLUSION:
      Performance of SF PCR was inferior while microcalorimetry was similar to culture
      but provided results considerably faster. [Clinical trial registration number
      (https://www.clinicaltrials.gov): NCT02530229].

PMID- 30219764
TI  - Real-world Experience of Using HLA-B*27 Tag-single-nucleotide Polymorphism Assay
      to Screen for Axial Spondyloarthritis.

PMID- 30219765
TI  - What Should Be the Primary Target of "Treat to Target" in Psoriatic Arthritis?
AB  - OBJECTIVE: Recommendations regarding "treat to target" in psoriatic arthritis
      (PsA) have stated that the target should be remission or inactive disease.
      Potential definitions include very low disease activity (VLDA), PsA Disease
      Activity Score (PASDAS) near remission, Disease Activity Index for PsA (DAPSA) or
      clinical DAPSA (cDAPSA) remission. Our aim was to investigate the proportion of
      patients who fulfill these definitions and how much residual active disease
      remained. METHODS: This analysis used 2 datasets: first, trial data from the
      Tight Control of PsA (TICOPA) study, which included 206 patients with recent
      onset (< 2 yrs) PsA receiving standard and biological disease-modifying
      antirheumatic drugs (DMARD); and second, an observational clinical dataset from
      Italy of patients receiving biological DMARD. Proportions achieving each of the 4
      potential targets were calculated in each dataset and comparisons between
      treatment groups were performed in the TICOPA dataset. Levels of residual disease
      were established for key clinical domains of PsA. RESULTS: All measures could
      differentiate the TICOPA trial treatment groups (p < 0.03). Lower proportions of
      patients fulfilled the VLDA criteria compared to DAPSA or cDAPSA remission.
      PASDAS results were different between the cohorts. Residual active disease was
      low across all definitions although higher levels were seen in DAPSA and cDAPSA
      compared to VLDA, particularly for psoriasis. In all measures, the proportion
      with elevated C-reactive protein was similar and low. CONCLUSION: VLDA appears
      the most stringent measure. It ensures that significant active arthritis,
      enthesitis, and psoriasis are not present, in contrast with DAPSA and PASDAS, in
      which composite scores can "hide" active disease in some domains.

PMID- 30219766
TI  - Presence of Autoantibodies in Erosive Hand Osteoarthritis and Association with
      Clinical Presentation.
AB  - OBJECTIVE: To investigate whether 3 rheumatoid arthritis-associated antibodies
      [rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) or
      anticarbamylated protein (anti-CarP) antibodies] are present in hand
      osteoarthritis (HOA) and associate with erosive OA (EOA). METHODS: Anti-CarP IgG
      was measured by ELISA in baseline sera of patients with HOA from 3 cohorts:
      HOSTAS (n = 510, 27.2% EOA), ECHO (n = 47), and EHOA (n = 23), and in sera of
      healthy controls (HC; n = 196, mean age 44.1 yrs, 51.0% women). Moreover, ACPA
      IgG and RF-IgM were additionally determined in HOSTAS and HC. The prevalence of
      autoantibodies was compared between HOA and HC and between erosive and nonerosive
      HOA. In HOSTAS, hand radiographs were scored (Kellgren-Lawrence, Osteoarthritis
      Research Society International osteophyte and joint space narrowing) and C
      reactive protein (CRP) levels, representing inflammation, were assessed. Groups
      were compared using nonparametric tests. RESULTS: The prevalence of anti-CarP was
      low and not significantly different between the total HOA group and HC (6.6% vs
      3.6%, p = 0.12). In HOSTAS, the prevalence of all tested autoantibodies was low
      (anti-CarP 7.1%, ACPA 0.8%, RF 6.1%), and there were no significant differences
      observed between HOA patients and HC or between erosive and nonerosive HOA.
      Further, radiographic damage and CRP levels were similar in anti-CarP+ and anti
      CarP-, and RF+ and RF- HOSTAS patients. CONCLUSION: The prevalence of
      autoantibodies is similar in HOA patients and HC, and these autoantibodies are
      not associated with erosive disease, structural damage, or inflammation in
      patients with HOA, indicating that another mechanism is driving erosive disease.

PMID- 30219767
TI  - Perceptions of Patients, Caregivers, and Healthcare Providers of Idiopathic
      Inflammatory Myopathies: An International OMERACT Study.
AB  - OBJECTIVE: Patient-reported outcome measures (PROM) that incorporate the patient
      perspective have not been well established in idiopathic inflammatory myopathies
      (IIM). As part of our goal to develop IIM-specific PROM, the Outcome Measures in
      Rheumatology (OMERACT) Myositis special interest group sought to determine which
      aspects of disease and its effects are important to patients and healthcare
      providers (HCP). METHODS: Based on a prior qualitative content analysis of focus
      groups, an initial list of 24 candidate domains was constructed. We subsequently
      conducted an international survey to identify the importance of each of the 24
      domains to be assessed in clinical research. Patients with IIM, their caregivers,
      and HCP treating IIM completed the survey. RESULTS: In this survey, a total of
      638 respondents completed the survey, consisting of 510 patients, 101 HCP, and 27
      caregivers from 48 countries. Overall, patients were more likely to rank
      "fatigue," "cognitive impact," and "difficulty sleeping" higher compared with
      HCP, who ranked "joint symptoms," "lung symptoms," and "dysphagia" higher. Both
      patients and providers rated muscle symptoms as their top domain. In general,
      patients from different countries were in agreement on which domains were most
      important. One notable exception was that patients from Sweden and the
      Netherlands ranked lung symptoms significantly higher compared to other countries
      including the United States and Australia (mean weighted rankings of 2.86 and
      2.04 vs 0.76 and 0.80, respectively; p < 0.0001). CONCLUSION: Substantial
      differences exist in how IIM is perceived by patients compared to HCP, with
      different domains prioritized. In contrast, patients' ratings across the world
      were largely similar.

PMID- 30219768
TI  - Radiologic and Pathological Investigation of Pseudarthrosis in Ankylosing
      Spondylitis: Distinguishing Between Inflammatory and Traumatic Etiology.
AB  - OBJECTIVE: To investigate the pathogenesis of pseudarthrosis in ankylosing
      spondylitis (AS) based on the pathological analysis of specimens harvested during
      surgery. METHODS: Radiographic and clinical data for 17 consecutive AS patients
      with pseudarthrosis were retrospectively analyzed. Meanwhile, the pathological
      analysis of specimens obtained during surgery was also performed. RESULTS: In
      total, 18 extensive Andersson lesions were included. Pseudarthrosis located at
      the apical region were noted in 12 patients. Complete ossified anterior
      longitudinal ligaments above or below pseudarthrosis and fracture through
      posterior elements or facet joints were observed in 7 and 6 lesions,
      respectively. The most definitive pathological characteristic in all cases was
      proliferating hypovascular edematous fibrous tissue involving disc, bone-disc
      border, and vertebral body. Fibrinoid necrosis, necrotic bone fragments,
      hemosiderin deposits, and active subchondral osteogenesis were found, indicating
      trauma process. Mild perivascular collections of inflammatory cells were detected
      in only 2 cases. CONCLUSION: AS-related pseudarthrosis is more likely to
      originate from mechanical trauma than inflammation. The above-mentioned
      radiological and histological findings showed that multiple mechanisms lead to
      the formation of pseudarthrosis. These mechanisms include excessive stress,
      insufficiency fracture, and an acute fracture involving a 3-column structure.

PMID- 30219769
TI  - New Features for Measuring Disease Activity in Pediatric Localized Scleroderma.
AB  - OBJECTIVE: To identify clinical features that define disease activity in
      pediatric localized scleroderma (LS), and determine their specificity and
      importance. METHODS: We conducted a multicenter prospective study of patients
      with active and inactive LS skin lesions. A standardized evaluation of a single
      designated study lesion per subject was performed at 3 visits. We evaluated the
      pattern and correlation between assessed features and physician's global
      assessments of activity (PGA-A). RESULTS: Ninety of 103 subjects had evaluable
      data; 66 had active and 24 inactive disease. Subjects had similar age of onset,
      sex, and disease patterns. Linear scleroderma was the most common subtype.
      Features specific for active disease included erythema, violaceous color, tactile
      warmth, abnormal skin texture, and disease extension. Scores for these variables
      changed over time and correlated with PGA-A of the lesion. Active and inactive
      lesions could not be distinguished by the presence or level of skin thickening,
      either of lesion edge or center. However, in active lesions, skin thickening
      scores did correlate with PGA-A scores. Regression analysis identified the
      combination of erythema, disease extension, violaceous color, skin thickening,
      and abnormal texture as predictive of PGA-A at study entry. Damage features were
      common irrespective of activity status. CONCLUSION: We identified variables
      strongly associated with disease activity, expanding upon those used in current
      measures, and determined their relative importance in physician activity scoring.
      Skin thickening was found to lack specificity for disease activity. These results
      will help guide development of a sensitive, responsive activity tool to improve
      care of patients with LS.

PMID- 30219770
TI  - The Effect of Pregnancy on Disease Activity in Patients with Psoriatic Arthritis.
AB  - OBJECTIVE: To evaluate the effect of pregnancy on disease activity in psoriatic
      arthritis (PsA). METHODS: This is a retrospective case series. Review of the
      medical files of all female patients followed at the PsA clinic of 2 medical
      centers identified those with at least 1 pregnancy during followup and 1 visit
      during or soon after pregnancy. RESULTS: Twenty-five women with PsA (out of 107
      women of reproductive age followed up in our PsA clinics) and 35 pregnancies were
      enrolled. Thirty-three pregnancies resulted in live healthy babies. In the whole
      group, there was no significant change in disease activity throughout pregnancy,
      while in 16 (48%) of pregnancies, patients worsened during the first postpartum
      year. In 15 out of 21 pregnancies, in which the women had been treated before
      conception with biologics, treatment was discontinued close to pregnancy or
      during the first trimester. Five of those 15 patients had been classified as
      having mild to severe PsA activity prior to pregnancy. That number increased to
      8, 9, and 14 during the first and second trimesters and postpartum period,
      respectively. There was no significant change in degree of disease activity in 6
      patients whose biologics were continued beyond the first trimester. Improvement
      in disease activity was observed during pregnancy among the nonbiologics-treated
      patients. Corticosteroids were initiated or the dosage was increased during 6
      pregnancies, all involving patients whose biologics were stopped before
      pregnancy. CONCLUSION: Continuation of biologics therapy was associated with a
      low level of disease activity and a low probability of flare during pregnancy.
      Stopping treatment with biologics before pregnancy is associated with flare
      during pregnancy and the postpartum period.

PMID- 30219771
TI  - Persistent Disease Activity Remains a Burden for Patients with Systemic Lupus
      Erythematosus.
AB  - OBJECTIVE: Persistent systemic lupus erythematosus (SLE) disease activity is
      associated with increased morbidity and mortality. In a multicenter cohort of
      patients with prevalent SLE, we described persistence, patterns, and predictors
      of change in disease activity over time. METHODS: Based on SLE Disease Activity
      Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups:
      low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to <= 10;
      MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed
      linear regression models were used to identify predictors of change over time in
      SLEDAI-2K. RESULTS: There were 2019 participants, with declining followup data
      over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort
      entry, mean (+/- SD) age was 42 (+/- 17) years, disease duration 11 (+/- 10)
      years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n =
      400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically
      important SLE activity. The proportion of patients in the LOW group at entry who
      moved to a higher activity level varied from 30% (167/557) at 1 year, to 49%
      (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to
      VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all
      analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor
      of higher SLEDAI-2K in subsequent years. CONCLUSION: Higher SLEDAI-2K at study
      entry was the single major independent predictor of higher SLEDAI-2K over time,
      reflecting frequent persistence of active disease, even in patients with
      longstanding disease. This highlights gaps in the optimal treatment of SLE.

PMID- 30219772
TI  - Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with
      over 2 Years Median Time in Treatment.
AB  - OBJECTIVE: Baricitinib is an oral, once-daily selective Janus kinase (JAK1/JAK2)
      inhibitor for adults with moderately to severely active rheumatoid arthritis
      (RA). We evaluated baricitinib's safety profile through 288 weeks (up to
      September 1, 2016) with an integrated database [8 phase III/II/Ib trials, 1
      longterm extension (LTE)]. METHODS: The "all-bari-RA" group included patients who
      received any baricitinib dose. Placebo comparison was based on the 6 studies with
      4 mg and placebo up to Week 24 ("placebo-4 mg" dataset). Dose response assessment
      was based on 4 studies with 2 mg and 4 mg including LTE data ("2 mg-4 mg
      extended"). The uncommon events description used the non-controlled all-bari-RA.
      RESULTS: There were 3492 patients who received baricitinib for 6637 total patient
      years (PY) of exposure (median 2.1 yrs, maximum 5.5 yrs). No differences in rates
      of death, adverse events leading to drug discontinuation, malignancies, major
      adverse cardiovascular event (MACE), or serious infections were seen for 4 mg
      versus placebo or for 4 mg versus 2 mg. Infections including herpes zoster were
      significantly more frequent for 4 mg versus placebo. Deep vein
      thrombosis/pulmonary embolism were reported with 4 mg but not placebo [all-bari
      RA incidence rate (IR) 0.5/100 PY]; the IR did not differ between doses (0.5 vs
      0.6/100 PY, 2 mg vs 4 mg, respectively) or compared to published RA rates. All
      bari-RA had 6 cases of lymphoma (IR 0.09/100 PY), 3 gastrointestinal perforations
      (0.05/100 PY), 10 cases of tuberculosis (all in endemic areas; 0.15/100 PY), and
      22 all-cause deaths (0.33/100 PY). IR for malignancies (0.8/100 PY) and MACE
      (0.5/100 PY) were low and did not increase with prolonged exposure. CONCLUSION:
      In this integrated analysis of patients with moderate to severe active RA with
      exposure up to 5.5 years, baricitinib has an acceptable safety profile in the
      context of demonstrated efficacy. Trial registration numbers: NCT01185353,
      NCT00902486, NCT01469013, NCT01710358, NCT01721044, NCT01721057, NCT01711359, and
      NCT01885078 at clinicaltrials.gov.

PMID- 30219773
TI  - The relevance of ceramides and their synthesizing enzymes for multiple sclerosis.
AB  - Ceramide synthases (CerS) synthesize chain length specific ceramides (Cer), which
      mediate cellular processes in a chain length-dependent manner. In experimental
      autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS),
      we observed that the genetic deletion of CerS2 suppresses EAE pathology by
      interaction with granulocyte-colony stimulating factor (G-CSF) signaling and CXC
      motif chemokine receptor 2 (CXCR2) expression, leading to impaired neutrophil
      migration. In the present study, we investigated the importance of Cers and their
      synthesizing/metabolizing enzymes in MS. For this purpose, a longitudinal study
      with 72 MS patients and 25 healthy volunteers was performed. Blood samples were
      collected from healthy controls and MS patients over 1- or 3-year periods,
      respectively. Immune cells were counted using flow cytometry, ceramide levels
      were determined using liquid chromatography-tandem mass spectrometry, and mRNA
      expression was analyzed using quantitative PCR. In white blood cells, C16-LacCer
      and C24-Cer were down-regulated in MS patients in comparison with healthy
      controls. In plasma, C16-Cer, C24:1-Cer, C16-GluCer, and C24:1-GluCer were up
      regulated and C16-LacCer was down-regulated in MS patients in comparison with
      healthy controls. Blood samples from MS patients were characterized by an
      increased B-cell number. However, there was no correlation between B-cell number
      and Cer levels. mRNA expression of Cer metabolizing enzymes and G-CSF signaling
      enzymes was significantly increased in MS patients. Interestingly, G-CSF receptor
      (G-CSFR) and CXCR2 mRNA expression correlated with CerS2 and UDP-glucose Cer
      glucosyltransferase (UGCG) mRNA expression. In conclusion, our results indicate
      that Cer metabolism is linked to G-CSF signaling in MS.

PMID- 30219774
TI  - Delayed lethal pulmonary air embolism after a gunshot head injury.
AB  - We present a case of a young male patient with a fatal pulmonary air embolism
      following a penetrating gunshot head injury. He suffered from severe head trauma
      including a laceration of the superior sagittal sinus. Operative neurosurgical
      intervention did not establish a watertight closure of the wounds. Eight days
      after the trauma, the patient suddenly collapsed and died after an attempt to
      mobilise him to the vertical. Forensic autopsy indicated pulmonary air embolism
      as the cause of death. Retrospectively, we postulate an entry of air to the
      venous system via the incompletely occluded wounds and the lacerated superior
      sagittal sinus while mobilisation to the vertical created a negative pressure in
      the dural sinus.

PMID- 30219775
TI  - Rare case of meningococcal sepsis-induced testicular failure, primary
      hypothyroidism and hypoadrenalism: Is there a link?
AB  - Severe illness can lead to multiple transient endocrinopathies. In adult
      patients, neuroendocrine alterations include sick euthyroid syndrome, an increase
      in corticosteroid levels, increase in prolactin levels, decreased insulin growth
      factor 1 levels and hypogonadism. We report the case of a 24-year-old man with
      meningococcal sepsis with multiple end-organ complications who developed
      persistent non-autoimmune hypothyroidism, adrenal insufficiency and primary
      hypogonadism all requiring hormone replacement. While adrenal insufficiency as
      part of the Waterhouse-Friderichsen syndrome is well described, reports of
      primary hypothyroidism and persistent primary hypogonadism in severe illness are
      exceedingly rare. Multiple combined endocrinopathies as in this case have not
      been reported previously. This case highlights the necessity of screening for
      endocrine abnormalities in severe illness and the need for treatment if
      persistent. It also raises a novel concept of meningococcal sepsis causing
      multiple endocrinopathies possibly via disseminated intravascular coagulopathy
      related ischaemic damage.

PMID- 30219776
TI  - Natural killer/T-cell lymphoma and secondary haemophagocytic lymphohistiocytosis
      in pregnancy.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal
      disorder. It is challenging to diagnose due to its rarity and variation in
      clinical presentation, laboratory abnormalities and underlying aetiologies. A
      reproductive-aged woman, gravida 2 para 1001 at 27 weeks gestation presented with
      fever, hypotension and subacute upper respiratory infection. She delivered a male
      infant by caesarean section secondary to fetal distress. Subsequently, she was
      diagnosed with T-cell lymphoma and secondary HLH. Despite management with
      supportive care and multiple chemotherapeutic agents, she ultimately died of
      multiorgan failure. Patients with HLH secondary to malignancy have a particularly
      poor prognosis. This case highlights the importance of considering secondary HLH
      in the differential diagnosis of a patient with fever, pancytopenia and systemic
      symptoms of unclear aetiology in pregnancy.

PMID- 30219777
TI  - Unilateral cataract associated with eyelid ash-leaf macule in tuberous sclerosis
      complex.
AB  - A 9-month-old male child with tuberous sclerosis complex presented with ash-leaf
      macules on the left periocular region and ipsilateral dense cataract. Fundus
      showed retinal astrocytic hamartomas. This case is reported for unilaterality of
      congenital cataract on the same side of eyelid ash-leaf macule in tuberous
      sclerosis.

PMID- 30219778
TI  - Common iliac artery thrombosis as a possible complication of the pluck technique
      in nephroureterectomy.
AB  - Common iliac artery (CIA) thrombosis is a rare surgical complication which may
      cause serious leg damage and may occasionally be fatal. We experienced two cases
      of CIA thrombosis in nephroureterectomy with the pluck technique for upper tract
      urothelial carcinoma. Patients were treated using emergent femoro-femoral bypass,
      and one patient was treated with fasciotomy of the lower extremity for
      compartment syndrome. CIA thrombosis is considered a possible complication of
      nephroureterectomy, particularly with the pluck technique in open surgery.
      Arterial thrombosis in intrapelvic surgery including nephroureterectomy should be
      carefully considered for patients at risk.

PMID- 30219779
TI  - Primary intracranial leiomyosarcoma among patients with AIDS in the era of new
      chemotherapeutic and biological agents.
AB  - Primary intracranial leiomyosarcoma (PIL) is a rare non-infectious aetiology of
      focal mass lesions among HIV-infected individuals. With only 16 published cases
      worldwide, information on its pathophysiology, risk factors, clinical course and
      management options is limited. We report two cases of PIL in HIV-infected
      Filipino men who presented with 1-3 months history of persistent headache,
      progressing in severity. Both had cranial MRI revealing intracranial mass
      diagnosed as leiomyosarcoma by excision biopsy and immunohistochemical staining.
      Both patients underwent adjuvant cranial radiotherapy and chemotherapy. Biologics
      were initiated in one patient. Both patients were alive with evidence of the
      disease.

PMID- 30219780
TI  - Chemotherapy in combination with stereotactic body radiation therapy (SBRT) for
      oligometastatic pancreatic cancer.
AB  - Metastatic pancreatic cancer is characterised by poor prognosis. High toxicity of
      chemotherapy limits its use in elderly patients with severe comorbidities.
      Meanwhile, in metastatic disease, local treatment did not show the positive
      effect on life expectancy. We present a clinical case of a 72-year-old woman with
      metastatic pancreatic adenocarcinoma tumour, node, metastases (T3N0M1) (according
      to the seventh TNM classification of the International Union Against Cancer).
      Chemotherapy led to partial response, but later was stopped due to severe
      toxicity. Thereafter, consolidating radiosurgical treatment was performed. Dose
      to pancreatic and liver lesions was 35 Gy in five fractions. After 9 months, only
      one liver lesion and primary pancreatic tumour, stable in size were determined by
      MRI. At present time, the patient is alive and in good condition, the disease is
      stable 50 months after stereotactic body radiation therapy (SBRT). SBRT provides
      a high level of local control and in combination with systemic treatment can
      potentially increase survival.

PMID- 30219781
TI  - Urachal adenocarcinoma.

PMID- 30219782
TI  - Recurrent pleural effusion in a young woman: calcifying fibrous tumour of the
      pleura.
AB  - We present the case of a 23-year-old woman with a long-standing history of
      recurrent left-sided pleural effusion unrelated to her menstrual cycle. At her
      last presentation, non-contrast-enhanced chest CT showed a pleural effusion and a
      lower left hemithorax mass, both large enough to cause complete collapse of the
      lower lobe and partial collapse of the upper lobe. Thoracoscopic surgery revealed
      a multilobulated mass originating from the dome of the diaphragm with pleural
      deposits. Histopathology diagnosed this as a calcifying fibrous tumour of the
      pleura, a rare benign tumour with excellent prognosis when completely excised.

PMID- 30219783
TI  - Unusual presentation of pancreatitis with extrapancreatic manifestations.
AB  - Pancreatitis, panniculitis and polyarthritis syndrome (PPP syndrome) is a rare
      and complex manifestation of pancreatitis that is currently reported in few
      cases. We present this case regarding a 77-year-old man who presented unusually
      with a 6-week history of bilateral lesions on his lower limbs. During this time,
      he experienced increasing fatigue, joint pain, and reported fevers and
      significant weight loss. An incidental serum amylase was found to be
      significantly elevated and remained elevated throughout his 2-month hospital
      stay. He never complained of abdominal pain or other typical symptoms of
      pancreatitis. Histological examination of the leg lesions reported evidence of
      fat necrosis and changes consistent with pancreatic panniculitis. An abdominal CT
      scan revealed a well-defined lesion posterior to the neck of the pancreas.
      Further examination by endoscopic ultrasound revealed chronic inflammatory
      changes. The patient experienced a long admission and was managed supportively
      until he was well enough to be discharged home.

PMID- 30219784
TI  - Continent cutaneous diversion pouch calculi.

PMID- 30219785
TI  - Periocular contact dermatitis with use of topical voriconazole 1% in mycotic
      keratitis.
AB  - We present two cases of culture-proven fungal keratitis on natamycin treatment
      which developed periocular erythema, oedema, burning sensation and pruritus
      within 48 hours of the addition of topical voriconazole. On clinical examination,
      periocular erythema with induration was noted. A diagnosis of orbital cellulitis
      was suspected, but the absence of pain and tenderness refuted the diagnosis on
      clinical grounds. A dermatology consultation was sought, and a diagnosis of
      periocular contact dermatitis with voriconazole was made. A skin patch test was
      performed with the same medication; however, it was negative. Topical
      voriconazole therapy was withdrawn, and the patient was prescribed cold
      compresses and oral antihistamine medication, to which they responded well.

PMID- 30219786
TI  - Concurrent internal hernia and intussusception after Roux-en-Y gastric bypass.

PMID- 30219787
TI  - Late twiddler syndrome in a patient with a submuscular implantable cardioverter
      defibrillator.

PMID- 30219788
TI  - Delayed pressure urticaria due to non-invasive blood pressure monitoring in a
      previously non-atopic man.

PMID- 30219789
TI  - Inhibitory effects of cannabidiol on voltage-dependent sodium currents.
AB  - Cannabis sativa contains many related compounds known as phytocannabinoids. The
      main psychoactive and nonpsychoactive compounds are Delta9-tetrahydrocannabinol
      (THC) and cannabidiol (CBD), respectively. Much of the evidence for clinical
      efficacy of CBD-mediated antiepileptic effects has been from case reports or
      smaller surveys. The mechanisms for CBD's anticonvulsant effects are unclear and
      likely involve noncannabinoid receptor pathways. CBD is reported to modulate
      several ion channels, including sodium channels (Nav). Evaluating the therapeutic
      mechanisms and safety of CBD demands a richer understanding of its interactions
      with central nervous system targets. Here, we used voltage-clamp
      electrophysiology of HEK-293 cells and iPSC neurons to characterize the effects
      of CBD on Nav channels. Our results show that CBD inhibits hNav1.1-1.7 currents,
      with an IC50 of 1.9-3.8 MUm, suggesting that this inhibition could occur at
      therapeutically relevant concentrations. A steep Hill slope of ~3 suggested
      multiple interactions of CBD with Nav channels. CBD exhibited resting-state
      blockade, became more potent at depolarized potentials, and also slowed recovery
      from inactivation, supporting the idea that CBD binding preferentially stabilizes
      inactivated Nav channel states. We also found that CBD inhibits other voltage
      dependent currents from diverse channels, including bacterial homomeric Nav
      channel (NaChBac) and voltage-gated potassium channel subunit Kv2.1. Lastly, the
      CBD block of Nav was temperature-dependent, with potency increasing at lower
      temperatures. We conclude that CBD's mode of action likely involves 1) compound
      partitioning in lipid membranes, which alters membrane fluidity affecting gating,
      and 2) undetermined direct interactions with sodium and potassium channels, whose
      combined effects are loss of channel excitability.

PMID- 30219790
TI  - Real-world stent retriever thrombectomy for acute ischemic stroke beyond 6 hours
      of onset: analysis of the NASA and TRACK registries.
AB  - BACKGROUND: The DEFUSE 3 and DAWN trials have shown the benefit of thrombectomy
      beyond 6 hours of stroke symptom onset in carefully selected patients. OBJECTIVE:
      To evaluate the real-world outcomes of stent retriever thrombectomy beyond 6
      hours of stroke onset using combined individual patient data from the North
      American Solitaire Stent Retriever Acute Stroke (NASA) and Trevo Stent-Retriever
      Acute Stroke (TRACK) registries. METHODS: Pooled analysis of individual patient
      data of all cases of anterior circulation acute ischemic stroke (AIS) from NASA
      and TRACK was performed to compare outcomes of patients presenting within the
      first hours 6 or beyond 6 hours of stroke symptom onset. RESULTS: Of 830 patients
      with anterior circulation AIS from the NASA and TRACK registries, 32.7% (271
      patients) underwent thrombectomy beyond the first 6 hours of symptom onset. The
      rates of good clinical outcome (modified Rankin scale score of 0-2 at 90 days),
      mortality, and symptomatic intracranial hemorrhage were similar: 48.1%, 20.6%,
      and 8.0% within 0-6 hours, 46.2%, 21.6%, and 10.9% within 6-16 hours, and 38.9%,
      33.3%, and 5% within 16-24 hours (p=0.8, 0.6, and 0.5, respectively). The rates
      of successful recanalization (Thrombolysis in Cerebral Infarction 2b/3) were
      79.4% in patients with stroke within 0-6 hours, 72.6% within 6-16 hours, and
      85.0% within 16-24 hours (p=0.04). CONCLUSIONS: Real-world experience with
      patients with anterior circulation AIS treated with the Solitaire and Trevo
      thrombectomy devices beyond the first 6 hours of symptom onset proved to be
      equally safe and effective as for patients with symptom onset within the first 6
      hours.

PMID- 30219791
TI  - Impaired drainage of vein of Labbe following venous sinus stenting for idiopathic
      intracranial hypertension.
AB  - PURPOSE: The impact of venous sinus stenting (VSS) on vein of Labbe (VOL)
      drainage is poorly understood. The purpose of the study is to examine the
      incidence and potential high risk factors of impaired VOL drainage among
      idiopathic intracranial hypertension (IIH) patients following VSS. MATERIALS AND
      METHODS: Institutional review board approved prospective evaluation of all IIH
      patients who underwent VSS over a 5 year period (January 2012 to December 2017)
      at Weill Cornell Medical Center constituted the study population. Patient
      demographics, procedural details (laterality of stenting, balloon angioplasty,
      number of stents, and stent diameters), morphology of the VOL and changes in the
      flow in the VOL, type of sinus stenosis, and transverse sinus symmetry were
      evaluated. We used chi2 analysis to evaluate impaired VOL drainage against other
      variables. Statistical significance was set at 0.05. RESULTS: 70 consecutive
      patients (67 women, 3 men) with a mean age of 31+/-9.8 years underwent VSS.
      Stenosis was extrinsic in 63% (n=44) and intrinsic in 37% (n=26) of patients.
      Impaired drainage of the VOL was detected in 9/70 (13%) patients. Ipsilateral VOL
      was recognized as dominant in 20% (n=14), co-dominant in 51% (n=36), and non
      dominant in 29% (n=20) of patients. Impaired VOL drainage was significantly
      associated with ipsilateral VOL dominance (P=0.001) and stent diameter of >=9 mm
      (P=0.042). All patients demonstrated widely patent VOL on follow-up contrast
      enhanced MR venography at 3 months and 24 months. CONCLUSION: Impaired drainage
      of the ipsilateral VOL is a potential consequence of VSS with 13% incidence, and
      has significant association with ipsilateral superficial cortical venous drainage
      via dominant VOL and stent diameter of >=9 mm. CLINICAL TRIAL REGISTRATION:
      NCT01407809.

PMID- 30219792
TI  - #Fake news: a systematic review of mechanical thrombectomy results among
      neurointerventional stroke surgeons on Twitter.
AB  - OBJECTIVE: Twitter is a popular social media platform among physicians.
      Neurointerventionalists frequently document their lifesaving mechanical
      thrombectomy cases on Twitter with very favorable results. We fear that there may
      be some social media publication bias to tweeted mechanical thrombectomy cases
      with neurointerventionalists being more likely to tweet cases with favorable
      outcomes. We used these publicly documented cases to analyze post-intervention
      Twitter-reported outcomes and compared these outcomes with the data provided in
      the gold standard literature. METHODS: Two reviewers performed a search of
      Twitter for tweeted cases of acute ischemic strokes treated with mechanical
      thrombectomy. Data were abstracted from each tweet regarding baseline
      characteristics and outcomes. Twitter-reported outcomes were compared with the
      Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke (HERMES)
      trial individual patient meta-analysis. RESULTS: When comparing the tweeted
      results to HERMES, tweeted cases had a higher post-intervention rate of modified
      Thrombolysis In Cerebral Infarction (mTICI) scale score of 2c/3 (94% vs 71%,
      respectively; p<0.0001) and rate of National Institutes of Health Stroke Scale
      (NIHSS) score <=2 (81% vs 21%, respectively; p<0.0001). There were no reported
      complications; thus, tweeted cases also had significantly lower rates of
      complications, including symptomatic intracerebral hemorrhage (0% vs 4.4%,
      respectively; p<0.0001), type 2 parenchymal hemorrhage (0% vs 5.1%, respectively;
      p<0.0001), and mortality (0% vs 15.3%, respectively; p<0.0001). CONCLUSIONS:
      There is a significant difference between social media and reality even within
      the 'MedTwitter' sphere, which is likely due to a strong publication bias in
      Twitter-reported cases. Content on 'MedTwitter', as with most social media,
      should be accepted cautiously.

PMID- 30219793
TI  - Predicting poor compliance with follow-up and intrauterine contraception services
      after medical termination of pregnancy.
AB  - BACKGROUND: Attendance at post-abortion follow-up visits is poor, but little is
      known about factors affecting it. OBJECTIVE: To assess the factors associated
      with non-compliance with post-abortion services and to evaluate differences in
      rates of attendance and intrauterine device (IUD) insertion according to the type
      of service provision. METHODS: 605 women undergoing a first trimester medical
      termination of pregnancy (MTOP) and planning to use intrauterine contraception
      were randomised into two groups. Women in the intervention group (n=306) were
      booked to have IUD insertion 1-4 weeks after the MTOP at the hospital providing
      the abortion, while women in the control group (n=299) were advised to contact
      their primary healthcare (PHC) centre for follow-up and IUD insertion. RESULTS:
      In the intervention group, 21 (6.9%) women failed to attend the follow-up visit,
      whereas in the control group 67 (22.4%) women did not contact the PHC to schedule
      a follow-up (p<0.001). In both groups, non-attendance was associated with history
      of previous pregnancy and abortion. Not having an IUD inserted within 3 months
      was significantly more common in the control group (73.6% (n=220)) than in the
      intervention group (9.2% (n=28), p<0.001). In the intervention group, predictive
      factors for not having an IUD inserted were anxiety, history of pregnancy and
      abortion. However, we identified no significant predictive factors in the control
      group. CONCLUSIONS: Factors predicting low compliance with post-MTOP follow-up
      are few. Comprehensive provision of abortion care and post-abortion services
      seems beneficial for minimising the loss to follow-up and delay in initiation of
      effective contraception. TRIAL REGISTRATION NUMBER: NCT01223521;Results.

PMID- 30219794
TI  - JUUL and other stealth vaporisers: hiding the habit from parents and teachers.
AB  - BACKGROUND: Some consumers wish to use vapour devices discreetly so that family
      members, teachers and coworkers do not recognise their use of nicotine
      ortetrahydrocannabinol (THC) laden vapour. METHODS: Stealthy vapour devices, as
      well as low-odour and low-vapour e-juices, were identified via a comprehensive
      online search between March and June 2018. RESULTS: As evidence of their
      popularity, a search for 'stealth vaping' on YouTube found 18 200 videos. A
      variety of cleverly designed vapour devices disguised as USB sticks, pens, remote
      controls, car fobs, smart phones, sweatshirt drawstrings and even asthma inhalers
      are on the market. JUUL, which resembles a USB stick, is the archetype of these
      devices and is especially popular among youth. A search of 'JUUL' on YouTube
      yielded 148 000 videos with 57 videos having >100 000 views. Searches on 'JUUL at
      school' (15 500), 'JUUL in class' (6840), 'hiding JUUL in school' (2030) and
      'JUUL in school bathroom' (1040) illustrate the product's popularity among
      students. Some e-juices promote themselves as having low visibility plumes while
      others profess to be of subtle odour to avoid detection. Numerous techniques have
      been described to hide the exhaled vapour plume such as by swallowing it or
      blowing it into one's clothing or into a backpack. CONCLUSIONS: The vaping
      industry has demonstrated much ingenuity in devising discreet vaporisers and de
      emphasising exhaled vapour plumes and their aroma. The US market for vaping
      devices with stealthy characteristics is anything but inconspicuous, with JUUL
      alone accounting for 70.5% of sales (July 2018).

PMID- 30219795
TI  - Electronic cigarette explosion and burn injuries, US Emergency Departments 2015
      2017.
AB  - BACKGROUND: Electronic cigarette (e-cigarette) battery failure can result in
      explosions and burn injuries. Previous attempts to quantify these events has been
      limited to compilations of case studies, federal agency reports and media
      reports. Although e-cigarette explosions and burn injuries are thought to be
      rare, current surveillance methods likely underestimate actual occurrences.
      METHODS: Analyses were conducted on cross-sectional data from the US Consumer
      Product Safety Commission's (CPSC) National Electronic Injury Surveillance System
      (NEISS). A keyword search of case narrative text was used to identify e-cigarette
      related explosion and burn injuries presenting to US emergency departments from
      2015 to 2017. Sampling weights were applied to make conservative national
      incidence estimates. RESULTS: From 2015 to 2017, there were an estimated 2035 e
      cigarette explosion and burn injuries presenting to US hospital emergency
      departments (95% CI 1107 to 2964). CONCLUSIONS: There are more e-cigarette
      explosion and burn injuries in the USA than estimated in the past reports.
      Improved surveillance of e-cigarette injuries and regulation of e-cigarette
      devices is urgently needed. NEISS could be a valuable resource for e-cigarette
      injury surveillance.

PMID- 30219797
TI  - Uninformed refusals: objections to enrolment in clinical trials conducted under
      an Exception from Informed Consent for emergency research.
AB  - Clinical trials in emergency situations present unique challenges, because they
      involve enrolling individuals who lack capacity to consent in the context of
      acute illness or injury. The US Department of Health and Human Services and Food
      and Drug Administration regulations allowing an Exception from Informed Consent
      (EFIC) in these circumstances contain requirements for community consultation,
      public disclosure and restrictions on study risks and benefits. In this paper, we
      analyse an issue raised in the regulations that has received little attention or
      analysis but is ethically complex. This challenge is when to solicit and honour
      objections to EFIC trial enrolment, including from non-legally appointed
      representatives. We address novel questions involving whose objections should be
      honoured, what level of understanding is necessary for objections to be
      considered valid and how hard investigators should work to offer an opportunity
      to object. We present a set of criteria that provide conceptual and practical
      guidance. We argue that objections should be honoured if they undermine one of
      the key assumptions that allows for the permissibility of EFIC trials: that
      individuals would likely not object to enrolment based on their values or
      preferences. We then clarify the practical implications of this approach through
      examination of three cases of refusal in an EFIC study.

PMID- 30219796
TI  - Estimated impact of the GST on tobacco products in India.
AB  - OBJECTIVE: To examine the potential impact of the goods and services tax (GST) on
      price, consumption and tax revenue from tobacco products in India and across
      states. METHODS: Data on prices, tax rates and tax revenue are used to estimate a
      benchmark scenario prior to the GST implementation in 2017-2018. Using own-price
      elasticity of demand for tobacco products, we estimate the impact of GST at the
      state level and the aggregate state-wise impact to obtain the national level
      impact. FINDINGS: We predict that the statutory GST rate of 28% plus compensation
      cess will increase the price of cigarettes, bidi and smokeless tobacco by 0.18%,
      8.8% and 6%, respectively, and, as a result, it will reduce the weighted average
      consumption by 0.3%, 10% and 6% and increase tax revenue by 0.17%, 35% and 4.7%,
      respectively. Most states will experience a fall in tax revenue from tobacco
      products by more than 50% compared with the value-added tax revenue they
      collected pre-GST. The GST compensation cess will have to be used to compensate
      states' revenue shortfalls. CONCLUSIONS: The GST has increased the complexity of
      the tax system for tobacco products. In particular, for cigarettes, the specific
      cess constitutes the majority of tax revenue, and therefore, it must be revised
      regularly to protect revenue and keep real prices from falling. In addition,
      India should reintroduce excise taxation on all tobacco products, at least in
      part, on top of the GST, to make them less affordable and to smooth the
      transition after the expiration of the compensation cess.

PMID- 30219798
TI  - B-type natriuretic peptide prevents postnatal closure of ductus arteriosus by
      both vasodilation and anti-remodeling in neonatal rats.
AB  - The physiologic process of postnatal ductus arteriosus (DA) closure consists of
      vasoconstriction followed by vascular remodeling. We have recently reported that
      B-type natriuretic peptide (BNP), a potent vasodilator, also has anti-remodeling
      effects in pulmonary vasculature. However, its effects on DA have not been
      elucidated. We investigated whether BNP can prevent DA closure, and if so, the
      underlying mechanisms. Using in vivo studies, we examined effects of BNP (10
      mg/kg, ip at birth) on DA closure in neonatal rats within 4 h after birth. We
      found that in control rats, the DA spontaneously closed at 4 h with a decreased
      DA diameter, enhanced intimal thickening, and luminal occlusion. BNP prevented DA
      closure at 4 h with a preserved DA diameter, attenuated intimal thickening, and
      preserved luminal patency. Ex vivo, BNP attenuated oxygen-induced
      vasoconstriction of isolated DA rings of newborn rats. These vasodilating effects
      were blunted by Rp-8-Br-PET-cGMPS, a cGMP inhibitor. In vitro, BNP inhibited
      angiotensin II (Ang II)-induced proliferation and migration of DA smooth muscle
      cells (DASMCs). BNP inhibited Ang II-induced mitochondrial reactive oxygen
      species (ROS) production and calcium overload in DASMCs. Finally, BNP inhibited
      Ang II-induced ERK1/2 activation. These in vitro effects were antagonized by Rp-8
      Br-PET-cGMPS. In conclusion, BNP prevents postnatal DA closure by both
      vasodilation and anti-remodeling through the cGMP pathway. The mechanisms
      underlying anti-remodeling effects include anti-poliferation and anti-migration,
      with attenuation of mitochondrial ROS production and intracellular calcium and
      ERK1/2 signaling. Therefore, the BNP/cGMP pathway can be a promising therapeutic
      target for clinical management of DA patency.

PMID- 30219799
TI  - Proteomic analysis of exosomes reveals an association between cell invasiveness
      and exosomal bioactivity on endothelial and mesenchymal cell migration in vitro.
AB  - Ovarian cancer has resulted in over 140 000 deaths reported annually worldwide.
      This is often attributed to cellular changes in the microenvironment, including
      increased migration of mesenchymal stem cells (MSCs) and endothelial cells (ECs)
      to facilitate metastasis. Recently, the ability of exosomes to communicate
      signals between cells (and promote cancer progression) has been established. In
      the present study, we explored the effect of exosomes on cells present in the
      tumour microenvironment. Exosomes were isolated from ovarian cancer cells with
      different invasive capacity (high = SKOV-3 and low = OVCAR-3) by differential and
      buoyant density centrifugation and characterised using nanoparticle tracking
      analysis (NTA), Western blot, and EM. Exosome secretion was positively correlated
      with invasiveness of releasing cells. Proteomic analyses identified common and
      unique proteins between exosomes from SKOV-3 and OVCAR-3 with gene ontology
      analyses revealing that these exosomes are involved in the regulation of cell
      migration. Since the tumour microenvironment contains multiple cell types,
      including MSCs and ECs, we examined the effect of these exosomes on MSC and EC
      migration. Exosomes promoted MSC and EC migration in a time- and concentration
      dependent manner. The effect of exosomes isolated from SKOV-3 on cell migration
      was significantly higher compared with exosomes from OVCAR-3. Thus, we suggest
      that exosomes from ovarian cancer cells contain a specific set of proteins that
      are representative of its cell of origin and the invasive capacity.

PMID- 30219800
TI  - Cardiovascular screening of Paralympic athletes reported by chief medical
      officers of the PyeongChang 2018 Paralympic Winter Games.

PMID- 30219801
TI  - Age, player position and 2 min suspensions were associated with match injuries
      during the 2017 Men's Handball World Championship (France).
AB  - AIM: To study the association between player characteristics, technical
      components of the game and the risk of match injuries during the 2017 Men's
      Handball World Championship. METHODS: Team physicians of the participating teams
      (n=24) were requested to provide injury report forms throughout the Men's
      Handball World Championship (France, January 2017). The individual time played,
      age, number of international matches played and all technical and penalty
      variables for each player were extracted from the official International Handball
      Federation (IHF) online database and used as risk factors in a general logistic
      linear model analysis. RESULTS: Of 387 players, 49 sustained one or more injuries
      (93 injuries in total). The total incidence of match injuries was 82.1 injuries
      per 1000 hours (95% CI 66.2 to 100.5), non-time-loss injury incidence was 40.6
      injuries per 1000 hours (95% CI 29.3 to 54.9), while time-loss injury incidence
      was 30.9 injuries per 1000 hours (95% CI 21.5 to 42.9). Multivariate analysis
      showed that age (OR 1.1, 95% CI 1.02 to 1.18, p=0.011), player position (backs:
      OR 6.79, 95% CI 2.25 to 20.54, p=0.001; goalkeepers: OR 5.03, 95% CI 1.15 to
      21.94, p=0.031) and 2 min suspensions (1-2 times: OR 2.77, 95% CI 1.27 to 6.04,
      p=0.011; 3 or more times: OR 2.66, 95% CI 1.18 to 6.38, p=0.029) were significant
      risk factors for getting injured during competition matches. CONCLUSION: Age,
      player position (backs, goalkeepers) and 2 min suspensions were associated with
      match injury. Stricter rule enforcement should be considered to prevent match
      injuries in elite handball.

PMID- 30219802
TI  - Concussion among military service academy members: identifying risk factors,
      recovery trajectories, and the role of mental health.

PMID- 30219803
TI  - Molecular ultrasound imaging of JAM-A depicts early arterial inflammation.

PMID- 30219804
TI  - Does photobiomodulation influence ageing?

PMID- 30219805
TI  - Combined Pre- and Postoperative Lymphocyte Count Accurately Predicts Outcomes of
      Patients with Colorectal Cancer.
AB  - BACKGROUND: Although preoperative lymphopenia is reportedly a prognostic factor
      in cancer patients, the association between postoperative lymphopenia and patient
      prognosis has not been widely studied. METHODS: We enrolled 379 patients who
      underwent surgery for colorectal cancer (CRC) to analyze correlations among pre-
      and postoperative lymphocyte counts (LCs) and prognosis in patients with CRC.
      RESULTS: Pre- and postoperative LCs were significantly correlated (r = 0.615, p <
      0.0001). Based on results of receiver operating characteristic analysis, patients
      were subgrouped as preoperative LC >=1,280 (pre-LCHigh, n = 234), preoperative LC
      < 1,280 (pre-LCLow, n = 145); and as postoperative LC >=680 (post-LCHigh, n =
      246), and postoperative LC < 680 (post-LCLow, n = 133). Five-year disease
      specific survival rates significantly differed between pre-LCHigh (88.6%) and pre
      LCLow (72.5%) groups (p < 0.0001); and also between the post-LCHigh (88.5%) and
      post-LCLow (71.1%) groups (p < 0.0001). Five-year disease-specific survival rates
      of patients who were both pre-LCLow and post-LCLow was significantly lower than
      those for patients who were either pre-LCHigh or post-LCHigh or pre-LCHigh/post
      LCHigh (p = 0.0003). Multivariate analysis indicated that the combination of pre-
      and postoperative LC was an independent prognostic indicator. CONCLUSIONS: The
      combination of pre- and postoperative LC is a predictive factor for prognosis in
      CRC patients.

PMID- 30219806
TI  - Breast Cancer in Pregnancy: A Retrospective Cohort Study.
AB  - Gestational breast cancer (GBC) is the second most commonly occurring malignancy
      affecting pregnant women. Management is complex due to potential foetal risks in
      the setting of maternal treatment. We report on the maternal, foetal, short-term
      neonatal and placental histopathologic findings of a retrospective cohort of
      pregnant women with either pre-gestational (group 1) or GBC (group 2) from a
      tertiary-level maternity care centre. Of the 69 women identified over 12 years,
      there were 47 in group 1 and 22 in group 2. Demographics, stage of breast cancer
      at diagnosis were similar in the 2 groups. Women with GBC (group 2) were more
      likely to receive surgery and chemotherapy or surgery alone as compared to those
      in group 1. No women with GBC received radiation during pregnancy, but 2 received
      this treatment postpartum. With regard to pregnancy outcomes, induction of labour
      was more common in women with GBC, as was preterm birth. Most preterm birth in
      women with GBC was late preterm, iatrogenic in nature to facilitate postpartum
      treatment. We conclude comparable pregnancy outcomes for women with GBC as
      compared to those with pregestational breast cancer.

PMID- 30219808
TI  - Abstracts from Plenary and Keynote Speakers.

PMID- 30219809
TI  - Submitted Abstracts from Summer School Participants.

PMID- 30219811
TI  - Optimal Prescriptions of Continuous Renal Replacement Therapy in Neonates with
      Hyperammonemia.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate patients' outcomes,
      determine the prescriptions of continuous renal replacement therapy (CRRT) that
      effectively reduce serum ammonia levels, and analyze the prognostic factors in
      neonates with hyperammonemia. METHODS: The medical records of 12 Korean neonates
      with inborn error of metabolism (IEM) who underwent CRRT for hyperammonemia were
      retrospectively analyzed. RESULTS: All patients received continuous venovenous
      hemodiafiltration. The median ultrafiltration rate (UFR) at the initiation of
      CRRT was 2,288.4 mL/h/1.73 m2. The median ammonia level at CRRT initiation was
      1,320 umol/L, and the median time to reduce the initial ammonia level by at least
      50% was 12.8 h. The survival rate during hospitalization was 83.3%. There were
      significant differences between patients with neurologic sequelae and those
      without poor outcomes in peak serum ammonia level before CRRT and serum ammonia
      level at CRRT initiation. CONCLUSION: This study suggested that CRRT could be a
      therapeutic option for neonates with IEM. However, it is necessary to raise the
      UFR above 4,000 mL/h/1.73 m2 in patients with high initial ammonia level.

PMID- 30219812
TI  - Physical Activity and Cognitive Function Among Older Adults with an Elevated
      Gamma Gap.
AB  - OBJECTIVE: We evaluated whether gamma gap is associated with cognitive function
      among older adults and whether physical activity is favorably associated with
      cognition among those with an elevated gamma gap. Materials (Subjects) and
      Methods:Data from the 1999-2002 NHANES were used to identify 2,352 older adults,
      ages 60-85. The gamma gap was evaluated from subtracting albumin from total
      protein (i.e., Gamma Gap = Total Protein (g/dl) - Albumin (g/dl). Those at or
      above 3.1 g/dl (31.0 g/L) were considered to have an elevated gamma gap. The
      Digit Symbol Substitution Test (DSST) was used to assess cognitive function tasks
      of pairing and free recall among participants. Participants were asked open-ended
      questions about participation in leisure-time physical activity over the past 30
      days. Results: Those with an elevated gamma gap (DSST, 44.8) had a lower
      cognitive function score when compared to those without an elevated gamma gap
      (DSST, 50.1) (P<0.001). After adjustments, and among those with an elevated gamma
      gap, those meeting MVPA guidelines (vs. not) had a DSST score 6.42 units higher
      (beta=6.42; 95% CI: 3.85-8.99; P<0.001).Conclusion:In this national sample of
      older adults, gamma gap was associated with cognitive function and, among those
      with an elevated gamma gap, meeting PA guidelines was associated with higher
      cognitive function. Relevant clinical implications are discussed, as gamma gap
      may be predictive of risk for early mortality and reduced quality of life.
      Experimental work is needed to investigate whether physical activity training
      programs are efficacious for meaningfully reducing an elevated gamma gap and
      preserving optimal cognitive functioning among at-risk individuals.

PMID- 30219813
TI  - Removal of Bilirubin with a New Adsorbent System: In Vitro Kinetics.
AB  - BACKGROUND/AIMS: Many potentially toxic molecules accumulate in the blood during
      hepatic dysfunction. In clinical practice, it is very difficult to remove
      bilirubin, the most widely studied toxin, and particularly the unconjugated form,
      strongly albumin-bound. The aim of this in vitro study was to assess irreversible
      bilirubin adsorption as a protein-bound compound marker, using Cytosorb(r)
      (Cytosorbents Corp.), a new hemoadsorption device designed to remove cytokines.
      METHODS: We performed 4 in vitro experiments, dynamic and static, with different
      albumin-bilirubin solutions. RESULTS: All experiments showed the resin's ability
      to break the albumin-bilirubin complex (Experiment 1, 2), leading to efficient
      bilirubin removal for 24 h (Removal Rate: 90% Experiment 3) with minimal albumin
      loss. No sign of bilirubin release from the charged resin was detected
      (Experiment 4). CONCLUSION: Cytosorb(r) seems a promising artificial liver
      support, thanks to its ability to adsorb bilirubin and its proven ability to
      modulate the cytokines involved in hepatic dysfunction.

PMID- 30219814
TI  - 57th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE).

PMID- 30219815
TI  - 57th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE).

PMID- 30219817
TI  - Colorectal Neuroendocrine Neoplasms - areas of unmet need.
AB  - The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well
      differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and
      poorly-differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according
      to the 2010 World Health Organisation (WHO) classification, has arguably not had
      as much attention or study as NENs occurring in other sites. Colorectal NETs and
      NECs are however easier to study than many others since they are usually not
      difficult to remove and are increasingly detected because of intensified
      colorectal cancer screening and surveillance programs. Colorectal NETs and NECs
      show site-specific heterogeneity with variable behaviour and different
      therapeutic options; these various aspects provide unique challenges. Because of
      bowel cancer screening programs, colorectal NENs, like conventional
      adenocarcinomas, may be diagnosed at a stage that is associated with improved
      survival. <br>In this article we intend to describe and define areas of unmet
      needs relating to the epidemiology, classification, pathology, diagnosis and
      therapy of colorectal NETs (including NETs G3), colorectal NECs, and finally,
      mixed adeno-neuroendocrine carcinomas (MANECs) by reviewing and discussing the
      relevant literature. <br>.

PMID- 30219816
TI  - Serum Lipopolysaccharide-Binding Protein is Associated with Chronic Inflammation
      and Metabolic Syndrome in Hemodialysis Patients.
AB  - BACKGROUND: In hemodialysis (HD) patients, impaired gut barrier and alteration in
      microbiota in the gut is thought to increase the risk of bacterial translocation
      and chronic inflammation. Lipopolysaccharide-binding protein (LBP) is an acute
      phase reactant that mediates immune responses triggered by microbial products.
      Our aim is to investigate the relationship between circulating levels of LBP, and
      various metabolic and inflammatory markers in HD patients. Besides, we also aim
      to determine its relationship among -patients with different body mass index.
      PATIENTS AND METHODS: A total of 123 HD patients were stratified into three 
      tertiles, according to serum LBP level. The LBP and inflammatory markers were
      determined using immunoassay methods. A bioimpedance spectroscopy device was used
      for body composition measurement. RESULTS: The serum levels of the two
      proinflammatory markers, high-sensitivity C-reactive protein (hsCRP) and
      interleukin (IL)-6, were significantly higher in patients in the upper tertile
      when compared with the rest of the tertiles. In HD patients, a significant
      positive correlation was found between serum LBP levels and CRP, IL-6, soluble
      CD14 (sCD14), and fasting blood glucose levels. Patients with metabolic syndrome
      and pre-existing cardiovascular disease had higher LBP levels than those without
      metabolic syndrome. Besides, obese patients were also associated with higher
      serum LBP levels. Multivariate regression analyses showed that IL-6 level was the
      strongest correlate of LBP level, followed by hsCRP level and sCD14. CONCLUSIONS:
      Our study suggested that elevated plasma LBP was associated with metabolic
      syndrome and obesity. In addition, increased LBP level was correlated positively
      to markers of inflammation, and sCD14 levels.

PMID- 30219818
TI  - Distinct Clinical Factors in Hospitalized Patients with Diverticular Bleeding and
      Diverticulitis.
AB  - BACKGROUND/AIMS: It is unclear why colonic diverticular bleeding and
      diverticulitis rarely coexist. This study compared the characteristics of these
      conditions. METHODS: This single-center retrospective study examined 310
      consecutive patients hospitalized with an episode of diverticular disease (cases)
      and outpatients without a diverticular episode (controls) from January 2012 to
      December 2015. We investigated distinct clinical factors in hospitalized patients
      with diverticular bleeding and diverticulitis. RESULTS: We identified 183
      patients with 263 episodes of diverticular bleeding and 127 patients with 135
      episodes of diverticulitis during the study period. Patients with diverticular
      bleeding were significantly older than those with diverticulitis (median age 76
      vs. 56 years) and had more cardiovascular disease, hypertension, diabetes,
      cerebrovascular disease, chronic kidney disease, lipid disorder, or a poorer
      performance status. Significantly more diverticular bleeding patients were taking
      antiplatelet drugs, anticoagulant drugs, proton pump inhibitors, or laxative
      agents. Multivariate analysis revealed that an age > 65 years (OR 5.42), and
      antiplatelet agent use (OR 7.29) were more significant risk factors for
      diverticular bleeding than for diverticulitis. CONCLUSIONS: Elderly people using
      antiplatelet drugs may be more susceptible to diverticular bleeding than
      diverticulitis.

PMID- 30219819
TI  - MicroRNA-7-5p Promotes Cisplatin Resistance of Cervical Cancer Cells and
      Modulation of Cellular Energy Homeostasis by Regulating the Expression of the
      PARP-1 and BCL2 Genes.
AB  - BACKGROUND Resistance to cisplatin results in recurrence or relapse of cervical
      cancer in women. An understanding of the mechanisms of cisplatin resistance will
      be important to improve the efficacy of cisplatin treatment. The aim of this
      study was to investigate the role of microRNA-7-5p (mir-7-5p) in cisplatin
      resistant cervical cancer cells in vitro. MATERIAL AND METHODS The expression
      levels of miR-7-5p were detected in cisplatin-resistant cervical cancer cells,
      HeLa, and SiHa cells (HPV16-positive), and in clinical tissue samples, using miR
      7-5p inhibition and a luciferase reporter assay. Fifteen paired cervical cancer
      tissue samples and adjacent normal cervical tissues were obtained from 15
      patients who underwent surgery for cervical cancer. Western blot and flow
      cytometry were used to investigate cell apoptosis. The expression of mir-7-5p was
      detected by quantitative real-time reverse transcription-polymerase chain
      reaction (qRT-PCR). RESULTS The level of miR-7-5p was increased in cisplatin
      resistant HeLa and SiHa cervical cancer cells. Increased expression of miR-7-5p
      inhibited DNA repair by modulating the expression of poly (ADP-ribose) polymerase
      1 (PARP-1), reducing energy consumption, and promoting autophagy via suppression
      of the expression of Bcl-2. These findings supported that increasing energy
      generation and reducing energy consumption, resulted in miR-7-5p maintaining
      energy homeostasis during cisplatin treatment. CONCLUSIONS The findings of this
      study showed that there was a protective role of miR-7-5p in cervical cancer
      cells treated with cisplatin and that miR-7-5p expression maintained energy
      homeostasis in cisplatin-resistant cervical cancer cells. However, miR-7-5p
      reduced energy consumption via inhibiting PARP-1 expression, and miR-7-5p
      increased energy generation by suppressing the expression of Bcl-2.

PMID- 30219820
TI  - Clinical Features of 167 Inpatients with Autosomal Dominant Polycystic Kidney
      Disease at a Single Center in China.
AB  - BACKGROUND The aim of this study was to describe the clinical characteristics of
      Chinese ADPKD inpatients and to identify the factors associated with disease
      severity. MATERIAL AND METHODS We included 167 hospitalized patients (inpatients)
      with ADPKD in this study. Multiple regression analyses were conducted to
      determine factors correlated with estimated glomerular filtration rate (eGFR).
      Patients were stratified into subgroups according to the presence of symptoms, in
      which clinical parameters were analyzed and compared. RESULTS The mean age of
      hospitalized ADPKD patients was 48.7 years old, lumbar and/or abdominal pain was
      seen in 40.12% of patients, following by nephrolithiasis (38.92%), hematuria
      (30.54%), and urinary tract infection (24.55%). Serum thrombocyte level and
      hemoglobin exhibited significant positive correlations with eGFR. Symptomatic
      patients accounted for 71.26% of the studied population. Patients with
      hypertension had increased risk of presence of symptoms (OR=2.794, 95%CI=1.341
      5.822). Low thrombocyte and hemoglobin levels were observed in patients with
      hematuria. CONCLUSIONS Thrombocyte level was positively correlated with eGFR but
      was not associated with presence of PKD-related symptoms, suggesting thrombocyte
      level might be an independent serum biomarker for disease progression.
      Hypertension was associated with increased risk of symptom occurrence, indicating
      the relationship between hypertension and disease progression. This study reveals
      the clinical characteristics of inpatients with ADPKD in China and provides
      clinicians with useful insights into this intractable disease.

PMID- 30219822
TI  - Local specific Immunoglobulin E among patients with nonallergic rhinitis: a
      systematic review.
AB  - BACKGROUND: Allergen specific immunoglobulin can be present in the nasal mucosa
      of patients with non-allergic rhinitis (NAR). This condition is defined as local
      allergic rhinitis. However, the reported presence of nasal specific
      immunoglobulin E (nspIgE) among NAR is variable. The aim of this review was to
      summarize the studies which reported the presence of nspIgE among patients
      diagnosed as NAR. METHODS: Embase (1947- ) and Medline (1946-) were searched
      until 6th June 2017. A search strategy was utilized to identify studies on nspIgE
      among patients with NAR. The target population was patients with symptoms of
      rhinitis, but negative systemic allergen sensitization. Studies with original
      data on detectable nspIgE among the NAR population were included. Meta-analysis
      of single proportions as a weighted probability %(95%CI) was performed.
      Heterogeneity was explored amongst studies. RESULTS: A search strategy returned
      2286 studies and 21 were included. These studies involved 648 participants with
      NAR. NspIgE was detected using either; 1. nasal secretions, 2. epithelial mucosa
      sampling, 3. tissue biopsies or 4. In-situ tests. Metaanalysis was performed on
      studies with nasal secretions. The weighted proportion of detectable nspIgE in
      nasal secretions within patients with NAR was 10.2 (7.4-13.4) %. Population
      definitions partly explained variability. Detection of nspIgE was lower in
      patients without a history suggestive of allergy compared to those with a
      positive allergic history (0 (0-3.1) % v 19.8 (14.5-25.6) %, p<0.01). CONCLUSION:
      NAR with positive allergy history suggests presence of nspIgE. These patients
      warrant further allergology evaluation to confirm localized nasal allergy, as
      they benefit from allergy therapy such as immunotherapy.

PMID- 30219821
TI  - Identification of the Risk HLA-A Alleles and Autoantigen in Han Chinese Vitiligo
      Patients and the Association of CD8+T Cell Reactivity with Disease
      Characteristics.
AB  - BACKGROUND Multiple studies have implicated a role for CD8+T cell-mediated immune
      response to autoantigens in vitiligo. However, the antigen-specific T lymphocyte
      reactivity against the peptide epitopes is diverse among different world
      populations. This study aimed to identify the risk HLA-A allele in vitiligo and
      study CD8+ T cell reactivity to 5 autoantigenic peptides in Han Chinese
      populations, and to analyze the association of CD8+ T cell reactivity with
      disease characteristics. MATERIAL AND METHODS The risk HLA-A allele was analyzed
      by case-control study. Enzyme linked immunospot (ELISPOT) assay was used to
      compare T cell reactivity to the 5 autoantigenic peptides between vitiligo
      patients and healthy controls, then we analyzed the association of CD8+ T cell
      reactivity to 2 positive peptides with disease activity and area of skin lesions.
      RESULTS The results indicated that the most frequent allele in the Han Chinese
      vitiligo patients was the HLA-A*02: 01 allele with a significantly higher
      frequency compared to controls (20.20% versus 13.79%, P=6.64*10-5). The most
      frequently encountered epitopes were 2 gp100 modified peptides, IMDQVPFSV and
      YLEPGPVTV, whereas a weak T cell reactivity against tyrosinase and Melan-A/MART-1
      were evaluated. Moreover, we demonstrated that T cell reactivity against the 2
      positive peptides was significantly associated with disease characteristics
      including disease activity and area of skin lesions. CONCLUSIONS Our findings
      showed that the HLA-A*02: 01 allele was the major risk HLA-A allele, and 2 gp100
      modified peptides were identified as autoantigens and were found to be closely
      related to disease characteristics which might play a critical role in Han
      Chinese vitiligo patients.

PMID- 30219823
TI  - Safety and Impact of Low-Dose Methotrexate on Endothelial Function and
      Inflammation in Individuals with Treated Human Immunodeficiency Virus: AIDS
      Clinical Trials Group Study A5314.
AB  - Background: Chronic inflammation in treated human immunodeficiency virus (HIV)
      infection is associated with mortality and atherosclerotic cardiovascular disease
      (ASCVD). We evaluated the safety and potential efficacy of low-dose methotrexate
      (LDMTX) in treated HIV. Methods: This was a phase II randomized, double-blind,
      multi-center trial in adults with treated HIV >=40 years old with CD4+ T-cells
      >=400 cells/mm 3 and with or at increased risk for ASCVD. Participants received
      LDMTX (5 to15 mg/week) or placebo (+ folic acid) for 24 weeks and were followed
      for an additional 12 weeks. Primary endpoints were safety and brachial artery
      flow-mediated dilation (FMD). Results: The 176 participants (90% male) had a
      median (Q1, Q3) age of 54 (49, 59) years. LDMTX was associated with decreases in
      CD4+ T-cells at week 24 and CD8+ T-cells at weeks 8, 12, and 24. Eleven
      participants (12.8%) experienced safety events in the LDMTX group versus 5 (5.6%)
      in the placebo group (?=7.2%, upper 1-sided 90% CI=13.4%; pnon
      inferiority=0.037). Week 24 change in FMD was 0.47% with LDMTX and 0.09% with
      placebo (p=0.55). No inflammatory markers changed differentially with LDMTX
      compared to placebo. Conclusion: In adults with HIV with or at increased risk for
      ASCVD, participants treated with LDMTX had more safety events than with placebo
      but the pre-specified non-inferiority margin of 15% was not exceeded. LDMTX had
      no significant effect on endothelial function or inflammatory biomarkers but was
      associated with a significant decrease in CD8+ T-cells. The balance of risks and
      potential benefits of LDMTX in this population will require additional
      investigation.

PMID- 30219824
TI  - Renal Dosing of Antibiotics: Are We Jumping the Gun?
AB  - Antibiotic renal dose adjustments are determined in subjects with stable chronic
      kidney disease and may not translate to patients in late phase trials and
      practice. Ceftolozane/tazobactam, ceftazidime/avibactam, and telavancin all carry
      precautionary statements for reduced clinical response in patients with baseline
      creatinine clearance 30 - 50 mL/min, potentially due to unnecessary dose
      reduction in the setting of acute kidney injury (AKI). In this review, we discuss
      the regulatory landscape for antibiotics eliminated by the kidney and highlight
      the importance of the first 48 hours of therapy. Using a clinical database, we
      identify AKI on admission in a substantial proportion of patients with pneumonia
      (27.1%), intra-abdominal (19.5%), urinary tract (20.0%), or skin and skin
      structure infections (9.7%) that resolved by 48 hours in 57.2% of cases. We
      suggest that deferred renal dose reduction of wide therapeutic index antibiotics
      could improve outcomes in patients with infectious diseases.

PMID- 30219825
TI  - Activity of hypothiocyanite and lactoferrin (ALX-009) against respiratory cystic
      fibrosis pathogens in sputum.
AB  - Objectives: To determine the antimicrobial activity of ALX-009, a combination of
      bovine lactoferrin and hypothiocyanite, in sputum against Pseudomonas aeruginosa
      and Burkholderia cepacia complex (Bcc), key pathogens causing infection in the
      lungs of cystic fibrosis (CF) patients. Methods: The antimicrobial activity of
      ALX-009 against clinical respiratory P. aeruginosa isolates was determined by
      time-kill assay. Sputum from CF patients was treated with ALX-009, either alone
      or in combination with tobramycin, and the effect on P. aeruginosa, Bcc and total
      sputum density was determined. Results: Time-kill assay indicated that ALX-009
      was bactericidal at 24 h against 4/4 P. aeruginosa isolates under aerobic
      conditions, and against 3/4 isolates under anaerobic conditions. ALX-009 was also
      bactericidal against P. aeruginosa in sputum samples at 6 h (n = 22/24 samples)
      and 24 h (n = 14/24 samples), and demonstrated significantly greater activity
      than tobramycin at both timepoints. Activity against Bcc in sputum samples (n =
      9) was also demonstrated, but the magnitude of change in Bcc density was less
      than for P. aeruginosa. To determine the effect of treating sputum with two doses
      of ALX-009, similar to current regimens for inhaled antibiotics, aliquots of a
      further 10 sputum samples positive for P. aeruginosa were treated with one (t = 0
      h) or two doses (t = 0 h, t = 12 h) of ALX-009; treatment with two doses resulted
      in bactericidal activity in 7/10 samples at 34 h compared with only 3/10 samples
      when treatment was with one dose. Conclusions: ALX-009 demonstrates promise as a
      novel antimicrobial that could be used to decrease P. aeruginosa density in the
      lungs of people with CF.

PMID- 30219826
TI  - Therapeutic drug monitoring; the need for practical guidance.

PMID- 30219828
TI  - Gas Forming Pyogenic Liver Abscess.

PMID- 30219827
TI  - PI4KIII inhibitor enviroxime impedes the replication of the hepatitis C virus by
      inhibiting PI3 kinases.
AB  - Objectives: Many positive-stranded RNA viruses, including HCV, drastically
      remodel intracellular membranes to generate specialized environments for RNA
      replication. Phosphatidylinositol 4-kinase III (PI4KIII)alpha plays an essential
      role in the formation of HCV replication complexes and has therefore been
      explored as a potential drug target. Here, we characterized the anti-HCV activity
      of the PI4KIII inhibitors enviroxime and BF738735 and elucidated their mechanism
      of action. Methods: Antiviral assays were performed using HCV subgenomic
      replicons and infectious HCV. Enviroxime- and BF738735-resistant HCV replicons
      were generated by long-term culture with increasing compound concentrations.
      Intracellular localization of phosphatidylinositol 4-phosphate (PI4P) lipids was
      analysed by confocal microscopy. Results: HCV subgenomic replicons resistant to
      either enviroxime or BF738735 proved cross-resistant and carried mutations in the
      NS3, NS4B and NS5A genes. Knockdown of PI4KIIIbeta by small interfering RNA
      (siRNA) did not affect the replication of the HCV subgenomic replicon in this
      study. Furthermore, the compounds did not affect PI4P lipid levels at the
      replication complexes nor the phosphorylation status of NS5A, activities
      attributed to PI4KIIIalpha. Interestingly, the broad-spectrum phosphoinositide 3
      kinase (PI3K) inhibitor LY294002 proved to be 10-fold less effective against the
      resistant replicons. In addition, enviroxime and BF738735 inhibited several PI3Ks
      in enzymatic assays. Conclusions: Contrary to assumptions, our data indicate that
      PI4KIIIalpha and PI4KIIIbeta are not the main targets for the anti-HCV activity
      of enviroxime and BF738735. Instead, we demonstrated that both molecules impede
      HCV replication at least partially by an inhibitory effect on PI3Ks. Moreover,
      HCV is able to bypass PI3K inhibition by acquiring mutations in its genome.

PMID- 30219829
TI  - Longitudinal study of ESBL Escherichia coli carriage on an organic broiler farm.
AB  - Objectives: To determine the molecular characteristics of ESBL-producing
      Escherichia coli (ESBL-E) collected during a longitudinal study on an organic
      broiler farm in order to investigate clonal expansion and horizontal gene
      transfer. Methods: Isolates were obtained from a longitudinal study performed
      previously on an organic broiler fattening farm. Samples from individually
      followed-up broilers, the broiler house, the transport van and persons that took
      the samples, taken at several timepoints (days 1, 3, 4, 7, 10, 42 and 70) within
      a production round and during the consecutive one (days 1, 2, 3 and 70), had been
      investigated for the occurrence of ESBL-E. In the current study, ESBL genes and
      MLST STs of these ESBL-E were determined. Plasmids were characterized and
      subtyped. Results: On arrival in round_1, ESBL-E of ST88 predominated, while on
      days 3, 4, 7 and 10 ST10 was most often found and at slaughter age ST155 and
      ST1551 prevailed. A shift in STs was also observed in round_2. None of the 35
      individually selected broilers followed up in round_1 was positive for the same
      ESBL-E ST at all sampling times. All isolates carried CTX-M-1 group genes,
      confirmed as blaCTX-M-1 in 158 isolates. Further analysis of 36 isolates of
      different STs showed blaCTX-M-1 on IncI1/ST3 plasmids. Conclusions: The rapid
      dissemination of ESBL-E on this broiler farm was not due to the spread of one
      specific E. coli clone, but most likely the result of horizontal transfer of an
      IncI1/ST3 plasmid carrying blaCTX-M-1 resulting in a shift in the predominant
      ESBL-E population in broilers.

PMID- 30219830
TI  - The Protective Effects of Informal Care Receipt against the Progression of
      Functional Limitations among Chinese Older People.
AB  - Objective: This study investigates the impacts of receiving informal care on the
      progression of functional limitations among older people aged 60 and over in
      China. Method: The data come from three waves of the China Health and Retirement
      Longitudinal Survey (CHARLS), which collected health and ageing-related
      information on a nationally representative sample of Chinese older people from
      2011 to 2015. Multilevel regression models were used to analyse the data.
      Results: The protective effect of receiving informal care is stronger for the
      first two years after the baseline survey and tends to fade away or be reversed
      four years later. The protective effect is stronger among older people receiving
      low-intensity informal care and is gradually weakened with an increase in care
      intensity. Discussion: Trajectories of function capabilities are deeply embedded
      in social relationships. In the context of rapid population ageing and increasing
      demand for informal care, government support for caregivers is needed to sustain
      the protective effects of informal care.

PMID- 30219831
TI  - Advancing research on psychological stress and aging with the Health and
      Retirement Study: Looking back to launch the field forward.
AB  - Objectives: The Health and Retirement Study (HRS) was designed as an
      interdisciplinary study with a strong focus on health, retirement, and
      socioeconomic environment, to study their dynamic relationships over time in a
      sample of mid-life adults. The study includes validated self-report measures and
      individual items that capture the experiences of stressful events (stressor
      exposures) and subjective assessments of stress (perceived stress) within
      specific life domains. Methods: This paper reviews and catalogs the peer-reviewed
      publications that have used the HRS to examine associations between psychological
      stress measures and psychological, physical health, and economic outcomes.
      Results: We describe the research to date utilizing HRS measures of the following
      stress types: traumatic and life events, childhood adversity, caregiving and
      other chronic stressors, discrimination, social strain and loneliness, work
      stress, and neighborhood disorder. We highlight how to take further advantage of
      the longitudinal study to test complex biopsychosocial models of healthy aging.
      Discussion: The HRS provides one of the most comprehensive assessments of
      psychosocial stress in existing population-based studies and offers the potential
      for a deeper understanding of how psychosocial factors are related to healthy
      aging trajectories. The next generation of research examining stress and
      trajectories of aging in the HRS should test complex longitudinal and mediational
      relationships, include contextual factors in analyses, and include more
      collaboration between psychologists and population health researchers.

PMID- 30219832
TI  - Seasonal Polyphenism in Bicyclus dorothea (Lepidoptera: Nymphalidae) Across
      Different Habitats in Cameroon.
AB  - Many organisms exhibit changes in phenotypic traits as a response to seasonal
      environmental variation. We investigated the role of habitat in generating
      seasonal polyphenism in different populations of the light bush brown butterfly
      Bicyclus dorothea (Cramer, 1779) (Lepidoptera: Nymphalidae) in Cameroon.
      Butterflies were caught during the wet and dry seasons across four localities
      representing two distinct habitats, namely forest and ecotone (forest-savanna
      transition zone) over a 2-yr period (2015-2016). We found distinct variation in
      the wing pattern characteristics of butterflies in response to seasonality and
      habitat. Specifically we observed that: 1) all wing characters are not seasonally
      plastic in B. dorothea; 2) populations from ecotone tend to be more variable,
      with individuals exhibiting wings with large spots during the wet season and very
      reduced spots in the dry season while in forest populations, individuals exhibit
      wings with large spots during the wet season, but in the dry season, spots are
      not as greatly reduced as their ecotone counterparts; 3) this polyphenism in B.
      dorothea alternated consistently during the wet and dry seasons over the 2 yr of
      sampling. Bicyclus species have become a textbook example of seasonal polyphenism
      while this study extends this model system to the unique forest-ecotone gradient
      of Central Africa and demonstrates the complexity of seasonal forms in different
      habitats.

PMID- 30219834
TI  - Interleukin-6 Trans-Signaling and Risk of Future Cardiovascular Events: A New
      Avenue for Atheroprotection?

PMID- 30219835
TI  - Polygenic approaches to detect gene-environment interactions when external
      information is unavailable.
AB  - The exploration of 'gene-environment interactions' (G * E) is important for
      disease prediction and prevention. The scientific community usually uses external
      information to construct a genetic risk score (GRS), and then tests the
      interaction between this GRS and an environmental factor (E). However, external
      genome-wide association studies (GWAS) are not always available, especially for
      non-Caucasian ethnicity. Although GRS is an analysis tool to detect G * E in
      GWAS, its performance remains unclear when there is no external information. Our
      'adaptive combination of Bayes factors method' (ADABF) can aggregate G * E
      signals and test the significance of G * E by a polygenic test. We here explore a
      powerful polygenic approach for G * E when external information is unavailable,
      by comparing our ADABF with the GRS based on marginal effects of SNPs (GRS-M) and
      GRS based on SNP * E interactions (GRS-I). ADABF is the most powerful method in
      the absence of SNP main effects, whereas GRS-M is generally the best test when
      single-nucleotide polymorphisms main effects exist. GRS-I is the least powerful
      test due to its data-splitting strategy. Furthermore, we apply these methods to
      Taiwan Biobank data. ADABF and GRS-M identified gene * alcohol and gene * smoking
      interactions on blood pressure (BP). BP-increasing alleles elevate more BP in
      drinkers (smokers) than in nondrinkers (nonsmokers). This work provides guidance
      to choose a polygenic approach to detect G * E when external information is
      unavailable.

PMID- 30219833
TI  - Longitudinal 5-Year Evaluation of Bone Density and Microarchitecture After Roux
      en-Y Gastric Bypass Surgery.
AB  - Context: Bone health declines in the initial years after Roux-en-Y gastric bypass
      (RYGB), but long-term skeletal effects are unclear. Objective: To document
      longitudinal changes in bone mineral density (BMD) and microarchitecture 5 years
      after RYGB. Design, Setting, and Participants: Prospective 5-year observational
      study of 21 adults with severe obesity receiving RYGB at an academic medical
      center. Main Outcome Measures: Spine and hip areal BMD were measured by dual
      energy X-ray absorptiometry, and trabecular volumetric BMD (vBMD) of the spine
      was assessed by quantitative CT (QCT). We measured vBMD and microarchitecture of
      the distal radius and tibia by high-resolution peripheral QCT in a subset of
      subjects. Serum type I collagen C-terminal telopeptide (CTX) and procollagen type
      I N-terminal propeptide (P1NP) were also measured. Results: Areal BMD declined by
      -7.8% +/- 7.6% at the spine and -15.3% +/- 6.3% at the total hip by 5 years after
      RYGB (P <= 0.001), although the rate of bone loss slowed in later years.
      Trabecular spine vBMD decreased by -12.1% +/- 12.3% by 5 years (P <= 0.001). At
      peripheral sites, vBMD continued to decrease steadily throughout 5 years, with
      parallel declines in cortical and trabecular microarchitecture, leading to
      decreases in estimated failure load of -20% and -13% at the radius and tibia,
      respectively (P < 0.001). Five years after RYGB, CTX and P1NP were 150% and 34%
      above baseline (P < 0.001 and P = 0.017, respectively). Conclusions: Sustained
      high-turnover bone loss and bone microarchitectural deterioration occur in the 5
      years after RYGB. Adults receiving RYGB warrant assessment of bone health.

PMID- 30219836
TI  - Quick approximation of threshold values for genome-wide association studies.
AB  - Standard normal statistics, chi-squared statistics, Student's t statistics and F
      statistics are used to map quantitative trait nucleotides for both small and
      large sample sizes. In genome-wide association studies (GWASs) of single
      nucleotide polymorphisms (SNPs), the statistical distributions depend on both
      genetic effects and SNPs but are independent of SNPs under the null hypothesis of
      no genetic effects. Therefore, hypothesis testing when a nuisance parameter is
      present only under the alternative was introduced to quickly approximate the
      critical thresholds of these test statistics for GWASs. When only the statistical
      probabilities are available for high-throughput SNPs, the approximate critical
      thresholds can be estimated with chi-squared statistics, formulated by
      statistical probabilities with a degree of freedom of two. High similarities in
      the critical thresholds between the accurate and approximate estimations were
      demonstrated by extensive simulations and real data analysis.

PMID- 30219837
TI  - lncSLdb: a resource for long non-coding RNA subcellular localization.
AB  - While long non-coding RNAs (lncRNAs) may play important roles in cellular
      function and biological process, we still know little about them. Growing
      evidences indicate that subcellular localization of lncRNAs may provide clues to
      their functionality. To facilitate researchers functionally characterize
      thousands of lncRNAs, we developed a database-driven application, lncSLdb, which
      stores and manages user-collected qualitative and quantitative subcellular
      localization information of lncRNAs from literature mining. The current release
      contains >11 000 transcripts from three species. Based on the accumulated region
      of lncRNAs, we classify transcripts into three basic localization types (nucleus,
      cytoplasm and nucleus/cytoplasm). In some conditions, the nucleus and cytoplasm
      types can be divided into three more accurate subtypes (chromosome, nucleoplasm
      and ribosome). Besides browsing and downloading data in lncSLdb, our system
      provides a set of comprehensive tools to search by gene symbols, genome
      coordinates or sequence similarity. We hope that lncSLdb will provide a
      convenient platform for researchers to investigate the functions and the
      molecular mechanisms of lncRNAs in the view of subcellular localization.

PMID- 30219838
TI  - WaspBase: a genomic resource for the interactions among parasitic wasps, insect
      hosts and plants.
AB  - Insect pests reduce yield and cause economic losses, which are major problems in
      agriculture. Parasitic wasps are the natural enemies of many agricultural pests
      and thus have been widely used as biological control agents. Plants, phytophagous
      insects and parasitic wasps form a tritrophic food chain. Understanding the
      interactions in this tritrophic system should be helpful for developing parasitic
      wasps for pest control and deciphering the mechanisms of parasitism. However, the
      genomic resources for this tritrophic system are not well organized. Here, we
      describe the WaspBase, a new database that contains 573 transcriptomes of 35
      parasitic wasps and the genomes of 12 parasitic wasps, 5 insect hosts and 8
      plants. In addition, we identified long non-coding RNA, untranslated regions and
      25 widely studied gene families from the genome and transcriptome data of these
      species. WaspBase provides conventional web services such as Basic Local
      Alignment Search Tool, search and download, together with several widely used
      tools such as profile hidden Markov model, Multiple Alignment using Fast Fourier
      Transform, automated alignment trimming and JBrowse. We also present a collection
      of active researchers in the field of parasitic wasps, which should be useful for
      constructing scientific networks in this field.

PMID- 30219839
TI  - Drug Target Commons 2.0: a community platform for systematic analysis of drug
      target interaction profiles.
AB  - Drug Target Commons (DTC) is a web platform (database with user interface) for
      community-driven bioactivity data integration and standardization for
      comprehensive mapping, reuse and analysis of compound-target interaction
      profiles. End users can search, upload, edit, annotate and export expert-curated
      bioactivity data for further analysis, using an application programmable
      interface, database dump or tab-delimited text download options. To guide
      chemical biology and drug-repurposing applications, DTC version 2.0 includes
      updated clinical development information for the compounds and target gene
      disease associations, as well as cancer-type indications for mutant protein
      targets, which are critical for precision oncology developments.

PMID- 30219841
TI  - Strengthen village malaria reporting to better target reservoirs of persistent
      infections in Southeast Asia.

PMID- 30219842
TI  - Improving the control of snakebite envenomation in Latin America and the
      Caribbean: a discussion on pending issues.

PMID- 30219840
TI  - SMMDB: a web-accessible database for small molecule modulators and their targets
      involved in neurological diseases.
AB  - High-throughput screening and better understanding of small molecule's structure
      activity relationship (SAR) using computational biology techniques have greatly
      expanded the face of drug discovery process in better discovery of therapeutics
      for various disease. Small Molecule Modulators Database (SMMDB) includes >1100
      small molecules that have been either approved by US Food and Drug
      Administration, are under investigation or were rejected in clinical trial for
      any kind of neurological diseases. The comprehensive information about small
      molecules includes the details about their molecular targets (such as protein or
      enzyme, DNA, RNA, antisense RNA etc.), pharmacokinetic and pharmacodynamic
      properties such as binding affinity to their targets (Kd, Ki, IC50 and EC50 if
      available), mode of action, log P-value, number of hydrogen bond donor and
      acceptors, their clinical trial status, their 2D and three-dimensional structures
      etc. To enrich the basic annotation of every small molecule entry present in
      SMMDB, it is hyperlinked to their description present in PubChem, DrugBank,
      PubMed and KEGG database. The annotation about their molecular targets was
      enriched by linking it with UniProt and GenBank and STRING database that can be
      utilized to study the interaction and relation between various targets involved
      in single neurological disease. All molecules present in the SMMDB are made
      available to download in single file and can be further used in establishing the
      SAR, structure-based drug designing as well as shape-based virtual screening for
      developing the novel therapeutics against neurological diseases. The scope of
      this database majorly covers the interest of scientific community and researchers
      who are engaged in putting their endeavor toward therapeutic development and
      investigating the pathogenic mechanism of various neurological diseases. The
      graphical user interface of the SMMDB is accessible on
      http://bsbe.iiti.ac.in/bsbe/smmdb.

PMID- 30219844
TI  - TCellXTalk facilitates the detection of co-modified peptides for the study of
      protein post-translational modification cross-talk in T cells.
AB  - Motivation: Protein function is regulated by post-translational modifications
      (PTMs) that may act individually or interact with others in a phenomenon termed
      PTM cross-talk. Multiple databases have been dedicated to PTMs, including recent
      initiatives oriented towards the in silico prediction of PTM interactions. The
      study of PTM cross-talk ultimately requires experimental evidence about whether
      certain PTMs co-exist in a single protein molecule. However, available resources
      do not assist researchers in the experimental detection of co-modified peptides.
      Results: Herein, we present TCellXTalk, a comprehensive database of
      phosphorylation, ubiquitination and acetylation sites in human T cells that
      supports the experimental detection of co-modified peptides using targeted or
      directed mass spectrometry. We demonstrate the efficacy of TCellXTalk and the
      strategy presented here in a proof of concept experiment that enabled the
      identification and quantification of 15 co-modified (phosphorylated and
      ubiquitinated) peptides from CD3 proteins of the T-cell receptor complex. To our
      knowledge, these are the first co-modified peptide sequences described in this
      widely studied cell type. Furthermore, quantitative data showed distinct dynamics
      for co-modified peptides upon T cell activation, demonstrating differential
      regulation of co-occurring PTMs in this biological context. Overall, TCellXTalk
      facilitates the experimental detection of co-modified peptides in human T cells
      and puts forward a novel and generic strategy for the study of PTM cross-talk.
      Availability: TCellXTalk is available at https://www.tcellxtalk.org. Source Code
      is available at https://bitbucket.org/lp-csic-uab/tcellxtalk. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30219843
TI  - HIV Associated Neurocognitive Impairment in Diverse Resource Limited Settings.
AB  - Background: Neurocognitive impairment remains a common complication of HIV
      despite effective antiretroviral therapy (ART). We previously reported improved
      neurocognitive functioning with ART initiation in seven resource limited settings
      (RLS) countries for HIV+ participants from AIDS Clinical Trials Group (ACTG) 5199
      (International Neurological Study (INS)). Here we apply normative data from the
      International Neurocognitive Normative Study (INNS) to INS, to provide previously
      unknown rates of neurocognitive impairment. Methods: A5199, INS assessed
      neurocognitive and neurological performance within a randomized clinical trial
      with 3 arms, containing WHO first line recommended ART regimens (ACTG 5175;
      PEARLS). ACTG 5271, INNS collected normative comparison data on 2400 high-risk
      HIV negatives from 10 voluntary counseling and testing (VCT) sites aligned with
      INS. Normative comparison data were used to create impairment ratings for HIV+
      participants in INS; associations were estimated using generalized estimating
      equations. Results: Among 860 HIV+ adults enrolled in ACTG 5199, 55% had no
      neurocognitive impairment at baseline. Mild neurocognitive impairment was found
      in 25%, moderate in 17% and severe in 3% of participants. With the initiation of
      ART, the estimated odds of impairment was reduced 12% (95% CI: 9%, 14%) for every
      24 weeks (p<.0001) on ART. Mild impairment dropped slightly, and then remained at
      about 18% out to week 168. Conclusions: Almost half of HIV+ participants had
      neurocognitive impairment at baseline before ART, based on local norms. With ART
      initiation, there were significant overall reductions in neurocognitive
      impairment over time, especially in those with moderate and severe impairments.

PMID- 30219845
TI  - Iron Status and Associated Malaria Risk Among African Children.
AB  - Background: It remains unclear whether improving iron status increases malaria
      risk, and few studies have looked at the effect of host iron status on subsequent
      malaria infection. We therefore aimed to determine whether a child's iron status
      influences their subsequent risk of malaria infection in sub-Saharan Africa.
      Methods: We assayed iron and inflammatory biomarkers from community-based cohorts
      of 1309 Kenyan and 1374 Ugandan children aged 0 - 7 years and conducted
      prospective surveillance for episodes of malaria. Poisson regression models were
      fitted to determine the effect of iron status on the incidence rate ratio of
      malaria using longitudinal data covering a period of 6 months. Models were
      adjusted for age, sex, parasitemia, inflammation and study site. Results: At
      baseline, the prevalence of iron deficiency (ID) was 36.9% and 34.6% in Kenyan
      and Ugandan children, respectively. Iron deficiency anemia (IDA) affected 23.6%
      of Kenyan and 17.6% of Ugandan children. Malaria risk was lower in children with
      ID (IRR = 0.7; 95% CI: 0.6, 0.8; p<0.001) and IDA (IRR = 0.7; 95% CI: 0.6, 0.9;
      p=0.006). Low transferrin saturation (<10%) was similarly associated with lower
      malaria risk (IRR = 0.8; 95% CI: 0.6, 0.9; p=0.016). However, variation in
      hepcidin, soluble transferrin receptors (sTfR) and hemoglobin / anemia was not
      associated with altered malaria risk. Conclusions: ID appears to protect against
      malaria infection in African children when defined using ferritin and transferrin
      saturation, but not when defined by hepcidin, sTfR or hemoglobin. Further
      research is required to determine causality.

PMID- 30219846
TI  - Engulfment and Cell Motility Protein 1 Protects Against DSS-induced Colonic
      Injury in Mice via Rac1 Activation.
AB  - Background and aims: Mucosal healing is an emerging therapeutic goal that could
      result in clinical remission of inflammatory bowel disease (IBD). We sought to
      determine the role of engulfment and cell motility protein 1 (ELMO1) in wound
      healing in vitro and in vivo and to investigate the underlying pathways. Methods:
      RNA transcriptome sequencing was performed to detect the expression profiles of
      mRNA between inflamed tissues and corresponding non-inflamed tissues of IBD
      patients, followed by GEO datasets and western blot analysis. The effects of
      ELMO1 overexpression or knockdown on cell migration and proliferation were
      determined. The dependence of these effects on Rac1 was assessed using a Rac1
      inhibitor (NSC23766) and a Rac1 pull-down assay. We identified the underlying
      pathways involved by Gene Ontology (GO) analysis. A dextran sulfate sodium (DSS)
      induced colitis model was established to evaluate the role of ELMO1 in colonic
      mucosal healing. Results: ELMO1 was upregulated in inflamed tissues compared with
      corresponding non-inflamed tissues. ELMO1 overexpression increased cell migration
      in a Rac1-dependent manner. Depletion of ELMO1 or NSC23766 administration
      abolished this effect. GO analysis revealed that ELMO1 overexpression
      preferentially affected pathways involved in cytoskeletal regulation and wound
      healing, which was demonstrated by enhanced F-actin staining and increased
      numbers of extending lamellipodia in cells overexpressing ELMO1. In DSS-induced
      colitis, systemic delivery of pSin-EF2-ELMO1-Pur attenuated colonic inflammation
      and promoted recovery from colonic injury. The protective effect of ELMO1 was
      dependent on Rac1 activation. Conclusions: ELMO1 protects against DSS-induced
      colonic injury in mice through its effect on epithelial migration via Rac1
      activation.

PMID- 30219848
TI  - Impact of health care reform on enrolment of immigrants in primary care in
      Ontario, Canada.
AB  - Objectives: In 2003, Ontario introduced a patient enrolment system as part of
      health care reforms, aimed at enhancing primary health care services, but it is
      unclear whether immigrants have benefited from this health care reform.
      Therefore, we studied whether this reform changed the extent of immigrants'
      enrolment in primary care services in Ontario between 2003 and 2012. Methods:
      This is a population-based retrospective cohort study, in which a closed cohort
      of 9231840 Ontario residents between 1985 and 2003 was created, using linked
      health administrative and immigration databases. Levels of enrolment for
      traditional and more comprehensive capitation-based practice between 2003 and
      2012 were compared by immigrant status. Logistic regression modelling was used to
      assess the odds of enrolment on primary care practices. Results: Overall
      enrolment in primary care practices increased gradually after 2004, until 2012,
      when two-thirds of the cohort (67%) were enrolled. The immigrants' enrolment
      level remained consistently lower than that of long-term residents over the study
      period. By 2012, enrolment of immigrants in capitation-based models was
      significantly lower (17.3% versus 25.4%). In particular, enrolment in Family
      Health Teams, considered the most comprehensive care model, was considerably
      lower in immigrants compared with long-term residents (5.6% versus 18.0%; OR =
      0.40, 95% CI: 0.40 to 0.41). Conclusions: Immigrant enrolment rates in new
      comprehensive primary care models were consistently lower than among long-term
      residents. This has implication on equitable primary care access for immigrant
      populations.

PMID- 30219847
TI  - Nuclear localization and phosphorylation modulate pathological effects of Alpha
      Synuclein.
AB  - Alpha-synuclein (aSyn) is a central player in Parkinson's disease (PD) but the
      precise molecular mechanisms underlying its pathogenicity remain unclear. It has
      recently been suggested that nuclear aSyn may modulate gene expression, possibly
      via interactions with DNA. However, the biological behavior of aSyn in the
      nucleus and the factors affecting its transcriptional role are not known. Here,
      we investigated the mechanisms underlying aSyn-mediated transcription
      deregulation by assessing its effects in the nucleus and the impact of
      phosphorylation in these dynamics. We found that aSyn induced severe
      transcriptional deregulation, including the downregulation of important cell
      cycle-related genes. Importantly, transcriptional deregulation was concomitant
      with reduced binding of aSyn to DNA. By forcing the nuclear presence of aSyn in
      the nucleus (aSyn-NLS), we found the accumulation of high molecular weight aSyn
      species altered gene expression and reduced toxicity when compared to the wild
      type or exclusively cytosolic protein. Interestingly, nuclear localization of
      aSyn, and the effect on gene expression and cytotoxicity, was also modulated by
      phosphorylation on serine 129. Thus, we hypothesize that the role of aSyn on gene
      expression and, ultimately, toxicity, may be modulated by the phosphorylation
      status and nuclear presence of different aSyn species. Our findings shed new
      light onto the subcellular dynamics of aSyn and unveil an intricate interplay
      between subcellular location, phosphorylation, and toxicity, opening novel
      avenues for the design of future strategies for therapeutic intervention in PD
      and other synucleinopathies.

PMID- 30219849
TI  - Suicide risk among Veteran primary care patients with current anxiety symptoms.
AB  - Background: Although anxiety is prevalent in primary care, the association
      between anxiety symptoms and suicide risk remains understudied. Objectives: This
      cross-sectional study aimed to (i) assess the prevalence of suicide risk among
      Veteran primary care patients with anxiety symptoms and (ii) compare suicide risk
      between patients with a positive (versus negative) depression screen. Methods:
      Participants were 182 adult primary care patients (84.6% male, Mage = 58.3 years)
      with current anxiety symptoms, but no psychotherapy in specialty care in the past
      year, at a Veterans Health Administration medical center in New York.
      Participants completed self-report measures of anxiety, depression and suicide
      risk via telephone. Results: Forty percent endorsed >=1 suicide risk item.
      Suicide risk was more common among those screening positive (versus negative) for
      depression (50.5% versus 26.5%, chi2 (1) = 10.88; P = 0.001). Participants with a
      negative depression screen constituted 31% of all those with any suicide risk.
      Logistic regression revealed that anxiety symptom severity was not associated
      with suicide risk (P = 0.14) after controlling for age, sex and depression screen
      status (P = 0.01). Conclusions: A substantial proportion of primary care patients
      with anxiety was classified as at risk for suicide, even in the absence of a
      positive depression screen. Primary care providers should assess suicide risk
      among patients with anxiety symptoms, even if the patients are not seeking
      specialty mental health treatment, the anxiety symptoms are not severe or do not
      rise to the level of an anxiety disorder, and comorbid depressive symptoms are
      not present.

PMID- 30219850
TI  - BhGLM: Bayesian hierarchical GLMs and survival models, with applications to
      Genomics and Epidemiology.
AB  - Summary: BhGLM is a freely available R package that implements Bayesian
      hierarchical modeling for high-dimensional clinical and genomic data. It consists
      of functions for setting up various Bayesian hierarchical models, including
      generalized linear models (GLMs) and Cox survival models, with four types of
      prior distributions for coefficients, i.e. double-exponential, Student-t, mixture
      double-exponential, and mixture Student-t. These functions adapt fast and stable
      algorithms to estimate parameters. BhGLM also provides functions for summarizing
      results numerically and graphically and for evaluating predictive values. The
      package is particularly useful for analyzing large-scale molecular data, i.e.
      detecting disease-associated variables and predicting disease outcomes. We here
      describe the models, algorithms and associated features implemented in BhGLM.
      Availability: The package is freely available from the public GitHub repository,
      https://github.com/nyiuab/BhGLM.

PMID- 30219851
TI  - Goldfish: An old and new model system to study vertebrate development, evolution,
      and human disease.
AB  - The goldfish (Carassius auratus) is a domesticated cyprinid teleost closely
      related to the crucian carp. Goldfish domestication occurred in South China
      around 1,000 years ago. At least 180 variants and 70 genetically established
      strains are currently produced. These strains possess diverse phenotypes in body
      shape, coloration, scales, and fin, eye, and hood morphology. These include
      biologically interesting phenotypes that have not been observed in mutants of
      zebrafish or medaka. In addition, goldfish strains have been maintained in a non
      wild environment for several hundreds of generations, and certain goldfish
      strains have phenotypes similar to some human diseases. The recent progress in
      the assembly of the whole genome sequence of goldfish provides strong tools for a
      genetic analysis of these phenotypes. The whole genome duplication (WGD) event
      occurred in the goldfish genome 8-14 million years ago; this is one of the latest
      WGD in vertebrates. Goldfish are a useful model for studying genome evolution
      after the WGD event. This review focuses on the potential for goldfish as a model
      system in understanding the molecular basis of vertebrate development and
      evolution and human diseases.

PMID- 30219852
TI  - Carbohydrate level and source have minimal effects on feline energy and
      macronutrient metabolism.
AB  - The carnivorous nature of the domestic cat makes feline metabolism of
      carbohydrates unique. The cats' glycemic response has been previously studied,
      with variable outcomes in response to carbohydrate level and source, but is an
      important response to understand how to control glycemia. The objectives of this
      study were to determine the glucose and insulin responses of cats fed 3
      commercial diets differing in carbohydrate content and source, and to investigate
      the effects of diet on RQ, energy expenditure (EE), and glycemic response.
      Domestic shorthair cats (=19, 10 males, 9 females) of similar age (4.3 +/- 0.48
      yr, mean +/- SD) and of ideal body condition score were used. Cats were fed, once
      a day, 1 of 3 commercial diets that differed in their perceived glycemic response
      (PGR; 36.8%, 30.7%, and 23.6% starch for high, medium, and low PGR, respectively)
      with cats cycling through all diets in 3 periods in 6 complete and 1 incomplete 3
      * 3 Latin square. Each period consisted of 8 d of adaptation to the diet,
      followed by 21-h calorimetry measurements, and real-time interstitial glucose
      measurements on day 9. On day 10, sequential blood sampling was completed to
      determine blood glucose and insulin. BW and ME intake did not differ among
      treatments. EE in the fasted state did not differ among treatments (P = 0.160),
      whereas postprandial EE was highest for the high PGR diet compared with the
      medium PGR and low PGR diets (P < 0.001). In conclusion, cats revealed a
      prolonged postprandial glucose and insulin response compared with other
      monogastric animals, yet diet effects were minimal. Overall, interstitial glucose
      measures were less variable than serum glucose measurements and followed a
      parallel pattern to RQ. Therefore, going forward, calorimetry and continuous
      interstitial glucose monitoring should be considered as less invasive
      alternatives to repeated blood sampling.

PMID- 30219853
TI  - Combining count- and length-based z-scores leads to improved predictions in non
      invasive prenatal testing.
AB  - Motivation: Non-invasive prenatal testing or NIPT is currently among the top
      researched topic in obstetric care. While the performance of the current state-of
      the-art NIPT solutions achieve high sensitivity and specificity, they still
      struggle with a considerable number of samples that cannot be concluded with
      certainty. Such uninformative results are often subject to repeated blood
      sampling and re-analysis, usually after two weeks, and this period may cause a
      stress to the future mothers as well as increase the overall cost of the test.
      Results: We propose a supplementary method to traditional z-scores to reduce the
      number of such uninformative calls. The method is based on a novel analysis of
      the length profile of circulating cell free DNA which compares the change in such
      profiles when random-based and length-based elimination of some fragments is
      performed. The proposed method is not as accurate as the standard z-score;
      however, our results suggest that combination of these two independent methods
      correctly resolves a substantial portion of healthy samples with an uninformative
      result. Additionally, we discuss how the proposed method can be used to identify
      maternal aberrations, thus reducing the risk of false positive and false negative
      calls. Availability: The open-source code of the proposed methods, together with
      test data, is freely available for non-commercial users at github web page
      https://github.com/jbudis/lambda. Supplementary Information: Supplementary
      materials are available at Bioinformatics online.

PMID- 30219854
TI  - Elevated CO2 (free-air CO2 enrichment) increases grain yield of aluminium
      resistant but not aluminium-sensitive wheat (Triticum aestivum) grown in an acid
      soil.
AB  - Background and Aims: Soil acidity currently limits root growth and crop
      production in many regions, and climate change is leading to uncertainties
      regarding future food supply. However, it is unknown how elevated CO2 (eCO2)
      affects the performance of wheat crops in acid soils under field conditions. We
      investigated the effects of eCO2 on plant growth and yield of three pairs of near
      isogenic hexaploid wheat lines differing in alleles of aluminium-resistant genes
      TaALMT1 (conferring root malate efflux) and TaMATE1B (conferring citrate efflux).
      Methods: Plants were grown until maturity in an acid soil under ambient CO2
      (aCO2; 400 umol mol-1) and eCO2 (550 umol mol-1) in a soil free-air CO2
      enrichment facility (SoilFACE). Growth parameters and grain yields were measured.
      Key Results : Elevated CO2 increased grain yield of lines carrying TaMATE1B by
      22 % and lines carrying only TaALMT1 by 31 %, but did not increase the grain
      yield of Al3+-sensitive lines. Although eCO2 promoted tiller formation, coarse
      root length and root biomass of lines carrying TaMATE1B, it did not affect ear
      number, and it therefore limited yield potential. By contrast, eCO2 decreased or
      did not change these parameters for lines carrying only TaALMT1, and enhanced
      biomass allocation to grains thereby resulting in increased grain yield. Despite
      TaMATE1B being less effective than TaALMT1 at conferring Al3+ resistance based on
      root growth, the gene promoted grain yield to a similar level to TaALMT1 when the
      plants were grown in acid soil. Furthermore, TaALMT1 and TaMATE1B were not
      additive in their effects. Conclusions: As atmospheric CO2 increases, it is
      critical that both Al3+-resistance genes (particularly TaALMT1) should be
      maintained in hexaploid wheat germplasm in order for yield increases from CO2
      fertilization to be realized in acid soils.

PMID- 30219855
TI  - Elucidating vancomycin-resistant Enterococcus faecium outbreaks: the role of
      clonal spread and movement of mobile genetic elements.
AB  - Background: Vancomycin-resistant Enterococcus faecium (VREfm) has emerged as a
      nosocomial pathogen worldwide. The dissemination of VREfm is due to both clonal
      spread and spread of mobile genetic elements (MGEs) such as transposons.
      Objectives: We aimed to combine vanB-carrying transposon data with core-genome
      MLST (cgMLST) typing and epidemiological data to understand the pathways of
      transmission in nosocomial outbreaks. Methods: Retrospectively, 36 VREfm isolates
      obtained from 34 patients from seven VREfm outbreak investigations in 2014 were
      analysed. Isolates were sequenced on a MiSeq and a MinION instrument. De novo
      assembly was performed in CLC Genomics Workbench and the hybrid assemblies were
      obtained through Unicycler v0.4.1. Ridom SeqSphere+ was used to extract MLST and
      cgMLST data. Detailed analysis of each transposon and their integration points
      was performed using the Artemis Comparison Tool (ACT) and multiple blast
      analyses. Results: Four different vanB transposons were found among the isolates.
      cgMLST divided ST80 isolates into three cluster types (CTs); CT16, CT104 and
      CT106. ST117 isolates were divided into CT24, CT103 and CT105. Within VREfm
      isolates belonging to CT103, two different vanB transposons were found. In
      contrast, VREfm isolates belonging to CT104 and CT106 harboured an identical vanB
      transposon. Conclusions: cgMLST provides a high discriminatory power for the
      epidemiological analysis of VREfm. However, additional transposon analysis is
      needed to detect horizontal gene transfer. Combining these two methods allows
      investigation of both clonal spread as well as the spread of MGEs. This leads to
      new insights and thereby better understanding of the complex transmission routes
      in VREfm outbreaks.

PMID- 30219856
TI  - Identification of novel genes involved in acetic acid tolerance of Saccharomyces
      cerevisiae using pooled-segregant RNA sequencing.
AB  - Acetic acid tolerance of the yeast Saccharomyces cerevisiae is manifested in
      several quantifiable parameters, of which the duration of the latency phase is
      one of the most studied. It has been shown recently that the latter parameter is
      mostly determined by a fraction of cells within the population that resumes
      proliferation upon exposure to acetic acid. The aim of the current study was to
      identify genetic determinants of the difference in this parameter between the
      highly tolerant strain MUCL 11987-9 and the laboratory strain CEN.PK113-7D. To
      this end, a combination of genetic mapping and pooled-segregant RNA sequencing
      was applied as a new approach. The genetic mapping data revealed four loci with a
      strong linkage to strain MUCL 11987-9, each containing still a large number of
      genes making the identification of the causal ones by traditional methods a
      laborious task. The genes were therefore prioritized by pooled-segregant RNA
      sequencing, which resulted in the identification of six genes within the
      identified loci showing differential expression. The relevance of the prioritized
      genes for the phenotype was verified by reciprocal hemizygosity analysis. Our
      data revealed the genes ESP1 and MET22 as two, so far unknown, genetic
      determinants of the size of the fraction of cells resuming proliferation upon
      exposure to acetic acid.

PMID- 30219857
TI  - Activity of plazomicin compared with other aminoglycosides against isolates from
      European and adjacent countries, including Enterobacteriaceae molecularly
      characterized for aminoglycoside-modifying enzymes and other resistance
      mechanisms.
AB  - Background: Plazomicin is a next-generation aminoglycoside that was developed to
      overcome common aminoglycoside-resistance mechanisms. Objectives: We evaluated
      the activity of plazomicin and comparators against clinical isolates collected
      from 26 European and adjacent countries during 2014 and 2015 as part of the
      Antimicrobial Longitudinal Evaluation and Resistance Trends (ALERT) global
      surveillance programme. Methods: All 4680 isolates collected from 45 hospitals
      were tested for susceptibility to antimicrobials using the reference broth
      microdilution method. Selected isolates were screened for genes encoding
      carbapenemases, aminoglycoside-modifying enzymes (AMEs) and 16S rRNA
      methyltransferases. Results: Plazomicin (MIC50/90 0.5/2 mg/L) inhibited 95.8% of
      Enterobacteriaceae at <=2 mg/L, including carbapenem-resistant Enterobacteriaceae
      (MIC50/90 0.25/128 mg/L). Plazomicin was more active compared with other
      aminoglycosides against isolates carrying blaKPC (MIC50/90 0.25/2 mg/L), isolates
      carrying blaOXA-48-like (MIC50/90 0.25/16 mg/L) and carbapenemase-negative
      isolates (MIC50/90 0.25/1 mg/L). Approximately 60% of the isolates harbouring
      blaVIM and blaNDM-1 carried 16S rRNA methyltransferases (mainly rmtB and armA).
      AME genes were detected among 728 isolates and 99.0% of these were inhibited by
      plazomicin at <=2 mg/L. Plazomicin activity against Pseudomonas aeruginosa
      (MIC50/90 4/8 mg/L) was similar to amikacin activity (MIC50/90 2/16 mg/L).
      Plazomicin demonstrated activity against CoNS (MIC50/90 0.12/0.25 mg/L) and
      Staphylococcus aureus (MIC50/90 0.5/1 mg/L). Plazomicin activity was limited
      against Acinetobacter spp. (MIC50/90 8/>128 mg/L), Enterococcus spp. (MIC50/90
      32/128 mg/L) and Streptococcus pneumoniae (MIC50/90 32/64 mg/L). Conclusions:
      Plazomicin demonstrated activity against Enterobacteriaceae isolates tested in
      this study, including isolates carrying AMEs and a high percentage of the
      carbapenem-non-susceptible isolates. Plazomicin displayed activity against
      staphylococci.

PMID- 30219858
TI  - l-Carnitine Improves Skeletal Muscle Fat Oxidation in Primary Carnitine
      Deficiency.
AB  - Context: Primary carnitine deficiency (PCD) is an inborn error of fatty acid
      metabolism. Patients with PCD are risk for sudden heart failure upon fasting or
      illness if they are not treated with daily l-carnitine. Objective: To investigate
      energy metabolism during exercise in patients with PCD with and without l
      carnitine treatment. Design: Interventional study. Setting: Hospital exercise
      laboratories and department of cardiology. Participants: Eight adults with PCD
      who were homozygous for the c.95A>G (p.N32S) mutation and 10 healthy age- and sex
      matched controls. Intervention: Four-day pause in l-carnitine treatment. Main
      outcome measures: Total fatty acid and palmitate oxidation rates during 1-hour
      submaximal cycle ergometer exercise assessed with stable isotope method (U13C
      palmitate and 2H2-d-glucose) and indirect calorimetry with and without l
      carnitine. Results: Total fatty acid oxidation rate was higher in patients with l
      carnitine treatment during exercise than without treatment [12.3 (SD, 3.7) vs 8.5
      (SD, 4.6) umol * kg-1 * min-1; P = 0.008]. However, the fatty acid oxidation rate
      was still lower in patients treated with l-carnitine than in the healthy controls
      [29.5 (SD, 10.1) umol * kg-1 * min-1; P < 0.001] and in the l-carnitine group
      without treatment it was less than one third of that in the healthy controls (P <
      0.001). In line with this, the palmitate oxidation rates during exercise were
      lower in the no-treatment period [144 (SD, 66) umol * kg-1 * min-1] than during
      treatment [204 (SD, 84) umol * kg-1 * min-1; P = 0.004) . Conclusions: The
      results indicate that patients with PCD have limited fat oxidation during
      exercise. l-Carnitine treatment in asymptomatic patients with PCD may not only
      prevent cardiac complications but also boost skeletal muscle fat metabolism
      during exercise.

PMID- 30219860
TI  - Corrigendum to "Chicken semen cryopreservation and use for the restoration of
      rare genetic resources".

PMID- 30219859
TI  - 3' end additions by T7 RNA polymerase are RNA self-templated, distributive and
      diverse in character-RNA-Seq analyses.
AB  - Synthetic RNA is widely used in basic science, nanotechnology and therapeutics
      research. The vast majority of this RNA is synthesized in vitro by T7 RNA
      polymerase or one of its close family members. However, the desired RNA is
      generally contaminated with products longer and shorter than the DNA-encoded
      product. To better understand these undesired byproducts and the processes that
      generate them, we analyze in vitro transcription reactions using RNA-Seq as a
      tool. The results unambiguously confirm that product RNA rebinds to the
      polymerase and self-primes (in cis) generation of a hairpin duplex, a process
      that favorably competes with promoter driven synthesis under high yield reaction
      conditions. While certain priming modes can be favored, the process is
      heterogeneous, both in initial priming and in the extent of priming, and already
      extended products can rebind for further extension, in a distributive process.
      Furthermore, addition of one or a few nucleotides, previously termed
      'nontemplated addition,' also occurs via templated primer extension. At last,
      this work demonstrates the utility of RNA-Seq as a tool for in vitro mechanistic
      studies, providing information far beyond that provided by traditional gel
      electrophoresis.

PMID- 30219862
TI  - Trees use more non-structural carbohydrate reserves during epicormic than basal
      resprouting.
AB  - Non-structural carbohydrates (NSCs) are crucial to support tree resprouting after
      disturbances that damage the crown or stem. Epicormic resprouting (from stem)
      could demand more from NSC reserves than basal resprouting (following top-kill),
      since epicormically resprouting trees need to maintain a greater living biomass.
      Yet, little is known about NSC use during epicormic resprouting, particularly the
      relative importance of stem and below-ground NSC reserves. We compared the
      distribution and magnitude of NSC decreases during epicormic and basal
      resprouting by experimentally removing crowns or stems of 14-year-old Eucalyptus
      obliqua L'Her. trees in native forest, then harvesting these trees over a 10
      month period (start, sprouts emerged, sprouts expanded) to measure changes in NSC
      concentration and mass by organ (stem, lignotuber, roots). We hypothesized that
      (i) NSC depletion during resprouting is primarily due to decreases in starch
      rather than soluble sugars concentrations; (ii) during epicormic resprouting,
      stem NSC concentrations are decreased irrespective of any decreases in roots; and
      (iii) absolute decreases in NSC mass are greater for epicormic than basal
      resprouting during the leafless period due to the carbon demands associated with
      maintaining greater living biomass. Results confirmed our hypotheses; starch was
      the primary storage carbohydrate, stems were an important source of starch during
      epicormic resprouting and carbon demands of maintenance functions were greater
      for epicormic resprouting, leading to greater decreases in NSC reserves. Roots
      were a more important starch storage organ than the lignotuber for both epicormic
      and basal resprouting. The proportional decrease in starch was severe for both
      modes of resprouting due to a long leafless period, after which trees resprouting
      epicormically relied on starch reserves for longer than those resprouting
      basally. It remains to be seen how the timing of disturbance affects the timing
      and vigour of resprouting, and how long-term NSC recovery differs for epicormic
      and basal resprouting.

PMID- 30219863
TI  - Talk to your gut: the oral-gut microbiome axis and its immunomodulatory role in
      the etiology of rheumatoid arthritis.
AB  - Microbial communities inhabiting the human body, collectively called the
      microbiome, are critical modulators of immunity. This notion is underpinned by
      associations between changes in the microbiome and particular autoimmune
      disorders. Specifically, in rheumatoid arthritis, one of the most frequently
      occurring autoimmune disorders worldwide, changes in the oral and gut microbiomes
      have been implicated in the loss of tolerance against self-antigens and in
      increased inflammatory events promoting the damage of joints. In the present
      review, we highlight recently gained insights in the roles of microbes in the
      etiology of rheumatoid arthritis. In addition, we address important
      immunomodulatory processes, including biofilm formation and neutrophil function,
      which have been implicated in host-microbe interactions relevant for rheumatoid
      arthritis. Lastly, we present recent advances in the development and evaluation
      of emerging microbiome-based therapeutic approaches. Altogether, we conclude that
      the key to uncovering the etiopathogenesis of rheumatoid arthritis will lie in
      the immunomodulatory functions of the oral and gut microbiomes.

PMID- 30219861
TI  - A synthetic free fatty acid-regulated transgene switch in mammalian cells and
      mice.
AB  - Trigger-inducible transgene expression systems are utilized in biopharmaceutical
      manufacturing and also to enable controlled release of therapeutic agents in
      vivo. We considered that free fatty acids (FFAs), which are dietary components,
      signaling molecules and important biomarkers, would be attractive candidates as
      triggers for novel transgene switches with many potential applications, e.g. in
      future gene- and cell-based therapies. To develop such a switch, we rewired the
      signal pathway of human G-protein coupled receptor 40 to a chimeric promoter
      triggering gene expression through an increase of intracellular calcium
      concentration. This synthetic gene switch is responsive to physiologically
      relevant FFA concentrations in different mammalian cell types grown in culture or
      in a bioreactor, or implanted into mice. Animal recipients of microencapsulated
      sensor cells containing this switch exhibited significant transgene induction
      following consumption of dietary fat (such as Swiss cheese) or under
      hyperlipidaemic conditions, including obesity, diabetes and lipodystrophy.

PMID- 30219864
TI  - SMAD7 in keratinocytes promotes skin carcinogenesis by activating ATM-dependent
      DNA repair and an EGFR-mediated cell proliferation pathway.
AB  - SMAD7 is a general inhibitor of transforming growth factor beta (TGF-beta)
      signaling that acts through interaction and degradation of TGF-beta receptors.
      SMAD7 has been demonstrated to be transcriptionally upregulated in chemical
      induced skin tumors and TGF-beta-treated normal keratinocytes. To evaluate the
      function of SMAD7 in skin carcinogenesis in vivo, Smad7 transgenic mice that
      specifically express either wild-type SMAD7 (TG-Smad7-WT) or mutant SMAD7 (TG
      Smad7-MT) in keratinocytes, as well as Smad7 keratinocyte-specific knockout
      (Smad72f/2f-K14Cre) mice were subjected to chemical-induced skin carcinogenesis.
      Wild-type SMAD7-expressing transgenic mice showed significantly greater papilloma
      formation than did non-TG control and Smad7-MT mice. The expression of WT-SMAD7
      attenuated DNA damage-induced apoptosis in epidermal keratinocytes by stimulating
      the ATM-dependent DNA repair pathway. Nonetheless, overexpression of WT-SMAD7
      caused a susceptibility to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      epidermal hyperproliferation through activation of epidermal growth factor (EGF)
      signaling. In agreement with the transgenic mouse data, keratinocyte-specific
      deletion of SMAD7 markedly suppressed the tumor formation by inhibiting ATM and
      EGFR signaling. Moreover, specific inhibition of EGFR signaling attenuated the
      hyperproliferation and tumor formation in TG-Smad7-WT mice. Taken together, these
      data support a novel role for SMAD7 as a tumor promoter in skin carcinogenesis
      where SMAD7 stimulates the DNA repair pathway and EGFR signaling activation.

PMID- 30219865
TI  - Quantitative assessment of DNA damage in the industrial ethanol production strain
      Saccharomyces cerevisiae PE-2.
AB  - Lignocellulosic hydrolysates remain one of the most abundantly used substrates
      for the sustainable production of second generation fuels and chemicals with
      Saccharomyces cerevisiae. Nevertheless, fermentation inhibitors such as acetic
      acid, furfural and hydroxymethylfurfural are formed during the process and can
      lead to slow or stuck fermentations and/or act as genotoxic agents leading to
      production strain genetic instability. We have developed a novel dominant
      deletion (DEL) cassette assay for quantification of DNA damage in both wild-type
      and industrial yeast strains. Using this assay, the ethanol production strain S.
      cerevisiae PE-2 was shown to be more resistant to hydrogen peroxide and furfural
      than the laboratory DEL strain RS112. Indeed, the PE-2 strain also showed a lower
      tendency for recombination, consistent with a more efficient DNA protection. The
      dominant DEL assay presented herein should prove to be a useful tool in the
      selection of robust yeast strains and process conditions for second generation
      feedstock fermentations.

PMID- 30219866
TI  - Post-Retirement Life Satisfaction and Financial Vulnerability: The Moderating
      Role of Control.
AB  - Objectives: This paper examines changes in life satisfaction around retirement
      exits for those with varying pre-retirement incomes, testing whether constraints
      on control and control over finances moderate the relationship between retiring
      and pre-retirement income. Method: This longitudinal study draws data from the
      2004-2014 waves of the HRS to examine changes in life satisfaction pre- versus
      post-retirement for three groups (the poor/near poor, financially vulnerable, and
      financially stable) of full-time workers ages 51 to 87 (N=970), and a subset
      (N=334) who fully retire over a four- year period. Results: Controlling for
      baseline life satisfaction, health, job/demographic characteristics, and social
      engagement, OLS regression results show financially stable retirees report higher
      levels of post-retirement life satisfaction relative to their full-time working
      counterparts, while the poor/near poor and the financially vulnerable report
      similar life satisfaction to those who continue working full-time. Constraints on
      personal control and control over finances moderate post-retirement life
      satisfaction for the financially vulnerable. Discussion: Results suggest full
      retirement predicts improved life satisfaction only for those most advantaged
      financially. Financially vulnerable older workers may adjust more effectively to
      retirement if they have access to resources that facilitate greater control over
      their lives.

PMID- 30219867
TI  - Longitudinal and Reciprocal Relationships Between Psychological Well-Being and
      Smoking.
AB  - Introduction: Smoking cessation treatments currently succeed at a rate of
      approximately 20-30%, underscoring the importance of exploring factors that might
      increase intervention effectiveness. While negative affect has been studied
      extensively in relation to smoking cessation, psychological well-being (PWB;
      e.g., life satisfaction, optimism, positive affect, purpose in life) has received
      little attention. This study tested longitudinal and reciprocal relationships
      between PWB and smoking status in older adults. Methods: Panel data were obtained
      from the biennial, longitudinal Health and Retirement Study. Using structural
      equation modeling, we developed cross-lagged models to examine the relationships
      of PWB in 2006 with smoking status in 2010 and of smoking status in 2006 with PWB
      in 2010 while controlling for covariates (Ns = 2939 to 4230, 55% women, 89%
      White, mean age = 64 years, mean years of education = 13, 25% smokers in 2006 and
      21% smokers in 2010). Separate cross-lagged models were developed for each of the
      PWB variables: life satisfaction, optimism, positive affect, and purpose in life.
      Results: Greater life satisfaction (standardized path coefficient = -0.04),
      optimism (standardized path coefficient = -0.07), and positive affect
      (standardized path coefficient = -0.08) in 2006 predicted a reduced likelihood of
      smoking in 2010. Being a smoker in 2006 predicted lower life satisfaction
      (standardized path coefficient = -0.25), optimism (standardized path coefficient
      = -0.10), positive affect (standardized path coefficient = -0.10), and purpose in
      life (standardized path coefficient = -0.13) in 2010. Conclusions: Findings
      warrant further exploration of the relationships between PWB and smoking, and
      support the incorporation of PWB-boosting components into existing treatments.

PMID- 30219868
TI  - NON-RADIOLOGICAL IMPACT OF A NUCLEAR EMERGENCY: PREPAREDNESS AND RESPONSE WITH
      THE FOCUS ON HEALTH.
AB  - Available experience from Chernobyl and Fukushima clearly demonstrate that
      nuclear emergencies may result in low and very low exposure levels, at which
      psychological and social effects among the affected population will dominate over
      the actual biological effects of ionising radiation. International protection
      standards and guidelines request, that both radiological and non-radiological
      health consequences have to be considered in preparedness and response to an
      actual emergency and there is a need to broaden the radiation protection system's
      philosophy beyond the metrics of radioactivity and radiation dose. During the
      past decade a number of multidisciplinary projects were set up with the aim of
      evaluating management options according to social, economic and ethical criteria,
      in addition to technical feasibility to achieve this goal. WHO and partners from
      the Inter-Agency Standing Committee Task Force on Mental Health and Psychosocial
      Support in Emergency Settings have developed a comprehensive framework and
      guidelines, which can be applied to any type of an emergency or disaster
      regardless of its origin. There is a need to include the available scientific
      expertise and the technical, managerial and personal resources to be considered
      within a similar 'decision framework' that will apply to radiation emergencies.
      Key areas of the required expertise needed to develop such a framework are
      radiation protection, medical support (especially primary care and emergency
      medicine, mental health support), social sciences (anthropology, psychology,
      ethics) and communications experts. The implementation of such a
      multidisciplinary concept in the operational world requires education and
      training well beyond the level currently available.

PMID- 30219869
TI  - Sensitivity and specificity of a lateral flow immunoassay (LFI) in serum samples
      for diagnosis of melioidosis.
AB  - Background: Culture is the gold standard for the diagnosis of melioidosis, an
      infection caused by Burkholderia pseudomallei. Here we evaluate a lateral flow
      immunoassay (LFI) to detect B. pseudomallei capsular polysaccharide (CPS) in
      serum samples. Methods: Patients with culture from any clinical specimen positive
      for B. pseudomallei were selected as cases. Patients who were blood culture
      positive for Staphylococcus aureus, Escherichia coli or Klebsiella pneumoniae as
      well as those who were malaria or dengue polymerase chain reaction assay positive
      were selected as controls. Results: The sensitivity of the LFI was 31.3% (60/192
      case patients [95% confidence interval {CI} 24.8 to 38.3]) and the specificity
      was 98.8% (559/566 control patients [95% CI 97.4 to 99.5]) in serum samples.
      Conclusions: Although LFI may have limited sensitivity in serum, it can rapidly
      diagnose melioidosis in resource-limited settings.

PMID- 30219870
TI  - Intervertebral Disk Degeneration and Repair.

PMID- 30219871
TI  - Cordycepin activates autophagy through AMPK phosphorylation to reduce
      abnormalities in Machado-Joseph disease models.
AB  - Machado-Joseph disease (MJD) is a neurodegenerative disorder, caused by an
      abnormal expansion of CAG trinucleotide repeats in the disease-causing gene. This
      mutation leads to an abnormal polyglutamine tract in the protein ataxin-3,
      resulting in formation of mutant ataxin-3 aggregates. Despite several attempts to
      develop a therapeutic option for MJD, currently there are no available therapies
      capable of delaying or stopping disease progression. Recently, our group reported
      that reducing the expression levels of mutant ataxin-3 lead to a mitigation of
      several MJD-related behavior and neuropathological abnormalities. Aiming a more
      rapid translation to the human clinics, in this study we investigate a
      pharmacological inhibitor of translation - cordycepin - in several preclinical
      models. We found that cordycepin treatment significantly reduced: i) the levels
      of mutant ataxin-3; ii) the neuropathological abnormalities in a lentiviral mouse
      model; iii) the motor and neuropathological deficits in a transgenic mouse model
      and iv) the number of ubiquitin aggregates in a human neural model. We
      hypothesize that the effect cordycepin is mediated by the increase of
      phosphorylated AMPK levels, which is accompanied by a reduction in the global
      translation levels and by a significant activation of the autophagy pathway.
      Overall, this study suggests that cordycepin might constitute an effective and
      safe therapeutic approach for MJD, and probably for the other polyglutamine
      diseases.

PMID- 30219872
TI  - Lifestyle behaviours and perceived well-being in different fire service roles.
AB  - Background: Aspects of the work environment influence employee well-being.
      However, it is unclear how employee lifestyle behaviours, health characteristics
      and well-being may differ within a broader occupational sector. Aims: To
      investigate the health characteristics, lifestyle behaviours and well-being of
      three Fire and Rescue Service (FRS) occupational groups that differ in shift work
      and occupational demands: operational firefighters (FF), emergency control (EC)
      and administrative support (AS) workers. Methods: Data were obtained via an
      online survey using previously validated questionnaires to assess health
      characteristics, lifestyle behaviours and perceived well-being. Differences
      between groups were explored, controlling for confounding variables, using
      analysis of covariance (ANCOVA) methods. Effect sizes are reported where
      appropriate to demonstrate clinical significance. Results: Four thousand five
      hundred and sixty-four FRS personnel volunteered, with 3333 (73%) completing the
      survey out of a total workforce of 60000 (8%). FF reported the lowest prevalence
      of chronic medical conditions (10%), compared with AS (21%) and EC (19%) workers.
      Total physical activity (PA) was 66% higher among FF compared with EC and AS
      workers. Components of sleep and self-rated health were independent predictors of
      well-being irrespective of FRS role. Conclusions: FF reported the highest levels
      of PA and highest perceptions of well-being, and the lowest prevalence of obesity
      and chronic medical conditions, compared with other FRS occupational groups.
      These findings may be used to inform FRS workplace intervention strategies.

PMID- 30219873
TI  - Longitudinal analysis of weight showed little relationship with age at puberty in
      gilts.
AB  - Continued selection for increased gilt body weight could negatively impact
      selection for age at puberty (AP) in gilts. The purpose of this study was to
      compare the genetic potential for growth to that for reducing age of puberty in
      swine. Females utilized (n = 1,079) were produced over a 6-yr period from a
      population developed to determine the impact of energy restrictions and genetic
      influences on sow development and longevity. From 120 to 235 d of age, BW was
      collected every 14 d and attainment of puberty tested. Age at puberty was defined
      as the first observed standing estrus in the presence of a mature boar. All
      females were genotyped with the Porcine SNP60K BeadChip and genotypes were used
      to construct a genomic relationship matrix. Univariate (AP), repeatability (BW),
      and random regression (BW; RR) models were fitted. Univariate analysis included
      the fixed effects of contemporary group (CG) and age at first boar exposure, and
      random direct additive and common litter effects. Repeatability analysis included
      the fixed effects of CG and random effects of direct additive, common litter, and
      permanent environmental (PE) effects. Random regression analysis included fixed
      effects of CG, and random direct additive, common litter, and PE effects.
      Proportion of phenotypic variation due to direct additive and common litter
      variance for AP were 0.33 and 0.06, respectively. Proportion of phenotypic
      variation due to direct additive, common litter, and PE variance estimated from
      the repeatability model for BW were 0.26, 0.11, and 0.40, respectively.
      Proportion of phenotypic variation due to direct additive, common litter, and PE
      variance estimated from the RR for BW ranged from (mean) 0.19 to 0.30 (0.27),
      0.08 to 0.31 (0.19), and 0.42 to 0.62 (0.50), respectively. Direct additive
      correlations between test days for BW from RR ranged from 0.30 to 0.99. Rank
      correlations between estimated breeding values (EBV) for AP and BW from the RR
      were near zero across all age points ranging from -0.03 to 0.09. Rank
      correlations were higher (0.63) when BW was considered at the age at which
      puberty was reached. Correlations between AP and BW EBV from the repeatability
      model were low (-0.11). Growth appears to be less related to AP than previously
      reported, suggesting the need to either directly measure AP or investigate
      alternative indicator traits. Selecting gilts with most desirable BW EBV alone
      would not result in improvement in AP, at least in the current population.

PMID- 30219874
TI  - Myeloperoxidase is a potential molecular imaging and therapeutic target for the
      identification and stabilization of high-risk atherosclerotic plaque.
AB  - Aims: As the inflammatory enzyme myeloperoxidase (MPO) is abundant in ruptured
      human atherosclerotic plaques, we aimed to investigate the role of MPO as a
      potential diagnostic and therapeutic target for high-risk plaque. Methods and
      results: We employed the tandem stenosis model of atherosclerotic plaque
      instability in apolipoprotein E gene knockout (Apoe-/-) mice. To test the role of
      MPO, we used Mpo-/-Apoe-/- mice and the 2-thioxanthine MPO inhibitor AZM198. In
      vivo MPO activity was assessed by liquid chromatography-tandem mass spectrometry
      detection of 2-chloroethidium generation from hydroethidine and by bis-5HT-DTPA
      Gd (MPO-Gd) molecular magnetic resonance imaging (MRI), while plaque phenotype
      was verified histologically. Myeloperoxidase activity was two-fold greater in
      plaque with unstable compared with stable phenotype. Genetic deletion of MPO
      significantly increased fibrous cap thickness, and decreased plaque fibrin and
      haemosiderin content in plaque with unstable phenotype. AZM198 inhibited MPO
      activity and it also increased fibrous cap thickness and decreased fibrin and
      haemosiderin in plaque with unstable phenotype, without affecting lesion
      monocytes and red blood cell markers or circulating leukocytes and lipids. MPO-Gd
      MRI demonstrated sustained enhancement of plaque with unstable phenotype on T1
      weighted imaging that was two-fold greater than stable plaque and was
      significantly attenuated by both AZM198 treatment and deletion of the Mpo gene.
      Conclusion: Our data implicate MPO in atherosclerotic plaque instability and
      suggest that non-invasive imaging and pharmacological inhibition of plaque MPO
      activity hold promise for clinical translation in the management of high-risk
      coronary artery disease.

PMID- 30219875
TI  - New Medtech Code of Ethics and Cardiology.

PMID- 30219876
TI  - Ian T Meredith MBBS PhD.

PMID- 30219877
TI  - Age in an Ageing Society.

PMID- 30219878
TI  - Henri Kulbertus is remembered by Luc Pierard.

PMID- 30219879
TI  - Assessing coronary plaques: non-invasive and intracoronary imaging and
      haemodynamic measurements.

PMID- 30219880
TI  - 'Ten Commandments' of the 2018 ESC Guidelines for the management of
      cardiovascular diseases during pregnancy.

PMID- 30219881
TI  - CardioS 2018.

PMID- 30219882
TI  - EHJ International Associate Editor.

PMID- 30219883
TI  - Personal Dust Exposure and Its Determinants among Workers in Primary Coffee
      Processing in Ethiopia.
AB  - Background: Coffee processing has been shown to cause high dust exposure among
      the workers, but there are few studies from primary processing of coffee, and
      none of them is from Ethiopia. The aim of this study was to assess dust exposure
      and its determinants among workers in primary coffee processing factories of
      Ethiopia. Methods: A total of 360 personal 'total' dust samples were collected
      from the breathing zone of workers in 12 primary coffee processing factories in
      Ethiopia. Dust sampling was performed with 25-mm three piece conductive cassettes
      with cellulose acetate filters attached to pumps with flow rate of 2 l min-1 for
      an average sampling duration of 410 min. The dust samples were analysed
      gravimetrically using a standard microbalance scale. An observational checklist
      was used to collect information about possible determinants of dust exposure in
      the work environment. Linear mixed effect regression models were used to identify
      significant determinants of total dust exposure. Results: Personal total dust
      exposure levels varied between the three main job groups with a geometric mean
      (GM) of 12.54 mg m-3 for the machine room workers, 12.30 mg m-3 for the transport
      workers, and 1.08 mg m-3 for hand pickers. In these three groups, 84.6%, 84.1%
      and 2.6% of the samples exceeded the occupational exposure limit for organic
      total dust of 5 mg m-3, respectively. The mixed-effects model for the machine
      room workers explained 21% of the total variance in total dust exposure, and
      showed that vigorously pouring coffee from a dropping height was associated with
      an about two times increase in exposure. For the transport workers, the mixed
      effects model that included pouring method of coffee beans, number of huller
      machine in the room, mixing coffee, and feeding hopper explained 32% of total
      variance in personal total dust exposure. Conclusion: About 84% of the dust
      samples among machine room and transport workers in primary coffee processing
      factories were above the occupational exposure limit value for organic dust.
      Proper control measures are necessary to reduce the exposure.

PMID- 30219884
TI  - Cesium Inhibits Plant Growth Primarily through Reduction of Potassium Influx and
      Accumulation in Arabidopsis.
AB  - Cesium (Cs+) is known to compete with the macronutrient potassium (K+) inside and
      outside of plants and inhibit plant growth at high concentrations. However, the
      detailed molecular mechanisms of how Cs+ exerts its deleterious effects on K+
      accumulation in plants are not fully elucidated. Here, we show that mutation in a
      member of the major K+ channel AKT1-KC1 complex renders Arabidopsis thaliana
      hypersensitive to Cs+. Higher severity of the phenotype and K+ loss was observed
      for these mutants in response to Cs+ than to K+ deficiency. Electrophysiological
      analysis demonstrated that Cs+, but not sodium, rubidium or ammonium,
      specifically inhibited K+ influx through the AKT1-KC1 complex. By contrast, Cs+
      did not inhibit K+ efflux through the homomeric AKT1 channel that occurs in the
      absence of KC1, leading to a vast loss of K+. Our observation suggests that
      reduced K+ accumulation due to blockage/competition in AKT1 and other K+
      transporters/channels by Cs+ plays a major role in plant growth retardation. This
      report describes the mechanical role of Cs+ in K+ accumulation, and in turn in
      plant performance, providing actual evidence at the plant level to what has long
      been believed; K+ channels are, therefore AKT1 is, "blocked" by Cs+.

PMID- 30219885
TI  - Cardiac autonomic activity during sleep in high altitude resident children
      compared to lowland residents.
AB  - Study Objectives: We aimed to characterize heart rate variability (HRV) during
      sleep in Andean children native to high altitude (HA) compared to age, gender and
      genetic ancestry-similar low altitude (LA) children. We hypothesized that the
      hypoxic burden of sleep at HA could induce variation in HRV. As children have
      otherwise healthy cardiovascular systems, such alterations could provide early
      markers of later cardiovascular disease. Methods: Twenty-six LA (14F) and 18 HA
      (8F) children underwent a single night of attended polysomnography. Sleep
      parameters and HRV indices were measured. Linear mixed models were used to assess
      HRV differences across sleep stage and altitude group. Results: All children
      showed marked fluctuations in HRV parameters across sleep stages, with higher
      vagal activity during NREM sleep and greater variability of the heart rate during
      REM. Moreover, HA children showed higher very low frequency HRV in REM sleep and,
      after adjusting for heart rate, higher low to high frequency ratio in REM sleep
      compared to children living at lower altitude. Conclusions: We confirmed previous
      findings of a stage-dependent modulation of HRV in Andean children living at both
      high and low altitudes. Moreover, we showed subtle alteration of HRV in sleep in
      HA children, with intriguing differences in the very low frequency domain during
      REM sleep. Whether these differences are the results of an adaptation to high
      altitude living, or an indirect effect of differences in oxyhaemoglobin
      saturation remain unclear, and further research is required to address these
      questions.

PMID- 30219887
TI  - Efficacy and Safety of Rivaroxaban versus Warfarin in Patients with Nonvalvular
      Atrial Fibrillation and a History of Cancer: Observations from ROCKET AF.
AB  - Aims: The management of anticoagulation therapy in patients with atrial
      fibrillation (AF) and cancer is challenging due to increased thrombotic and
      bleeding risks. We sought to determine the safety and efficacy of rivaroxaban in
      patients with AF and a history of cancer. Methods and Results: ROCKET AF
      randomized 14,264 patients with AF to rivaroxaban or warfarin with a median
      follow-up of 1.9 years. Cox regression models were used to assess the association
      between cancer history and clinical outcomes, and the relative treatment effect
      of rivaroxaban versus warfarin in these patients. A total of 640 patients
      enrolled in ROCKET AF had a history of cancer, with the most common types being
      prostate (28.6%), colorectal (16.1%), and breast (14.7%) cancer. Patients with a
      history of cancer were older, more frequently male, more likely to have prior VKA
      use, and had higher rates of overall bleeding (HR 1.30 95% CI 1.16-1.47; p <
      0.0001) and non-cardiovascular death (HR 1.47 95% CI 1.04-2.07; p = 0.031)
      compared with those with no cancer history. There were no significant
      associations between cancer history and stroke, venous thromboembolism, or
      myocardial infarction. The relative efficacy of rivaroxaban versus warfarin for
      prevention of stroke/systemic embolism was similar in those with and without a
      history of cancer (interaction p-value=0.21). Conclusion: In ROCKET AF, a history
      of cancer was associated with a higher risk of bleeding and non-cardiovascular
      death, but not ischemic events. The relative efficacy and safety of rivaroxaban
      compared with warfarin were not significantly different in patients with and
      without a history of cancer. The results of this study are exploratory and should
      be taken in context of the study population, which may not be generalizable to
      those with advanced malignancy. Further investigation is needed to understand
      optimal anticoagulation strategies in patients with AF and cancer.

PMID- 30219886
TI  - 9 weeks vs 1 year adjuvant trastuzumab in combination with chemotherapy: final
      results of the phase III randomized Short-HER study.
AB  - Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant
      treatment for HER2-positive breast cancer. The efficacy of less extended
      trastuzumab exposure is under investigation. The Short-HER study was aimed to
      assess the non-inferiority of 9 weeks vs 1 year of adjuvant trastuzumab combined
      with chemotherapy. Patients and methods: HER2-positive breast cancer patients
      with node-positive or, if node negative, with at least one risk factor (pT > 2cm,
      G3, lympho-vascular invasion, Ki-67>20%, age <=35 years, or hormone receptor
      negativity) were randomly assigned to receive sequential anthracycline-taxane
      combinations plus 1-year trastuzumab (arm A, long) or plus 9-weeks trastuzumab
      (arm B, short). This study was designed as a non-inferiority trial with disease
      free survival (DFS) as primary end-point. A DFS Hazard Ratio (HR) <1.29 was
      chosen as the non-inferiority margin. Analyses according to the frequentist and
      Bayesian approach were planned. Secondary endpoints included 2-year failure rate
      and cardiac safety. Results: 1254 patients from 82 centers were randomized (arm
      A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and
      85% in the short arm. The HR was 1.13 (90%CI 0.89;1.42), with the upper limit of
      the CI crossing the non-inferiority margin. According to the Bayesian analysis,
      the probability that the short arm is non-inferior to the long one is 80%. The 5
      yr OS is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90%CI0.74;1.56).
      Cardiac events are significantly lower in the short arm (risk-ratio 0.33,
      95%CI0.22;0.50, p < 0.0001). Conclusions: This study failed to show the non
      inferiority of a shorter trastuzumab administration. 1-year trastuzumab remains
      the standard. However, a 9-week administration decreases the risk of severe
      cardiac toxicity and can be an option for patients with cardiac events during
      treatment and for those with a low risk of relapse.

PMID- 30219888
TI  - The inflammation-based index can predict response and improve patient selection
      in NETs treated with PRRT: a pilot study.
AB  - Background: Peptide Receptor Radionuclide Therapy (PRRT) is an effective
      treatment for certain patients with metastatic neuroendocrine tumours (NETs).
      Tumour response is highly variable; no biomarker in clinical practice has been
      demonstrated to reliably predict outcome. The Inflammation-Based Index (IBI),
      derived from serum C-reactive protein and albumin levels, predicts survival and
      response to treatment in patients in a number of cancer types and was therefore
      explored in this setting. Materials and Methods: Clinico-pathological data from
      patients undergoing PRRT for metastatic NETs were collected at baseline and
      during treatment. The primary endpoint was progression free survival (PFS) with a
      secondary endpoint of overall survival (OS). Cox regression analysis tested
      associations between baseline variables and their dynamic changes, and PFS and
      OS. Decision curve analysis (DCA) was used to determine the net benefit
      associated with a treatment strategy determined by the baseline IBI and non
      response to PRRT. Results: Fifty-five patients were recruited. Baseline IBI >0
      was associated with inferior PFS (HR 14.2 (95% CI 5.25-38.5), p<0.001) and OS
      (p<0.001). Multivariate analysis confirmed an independent association between IBI
      and PFS (p=0.001). DCA indicated a net clinical benefit at risk thresholds
      between 0.03 and 0.58. Conclusion: Baseline IBI score and its dynamic change
      through treatment are associated with both PFS and OS. At a risk threshold
      equivalent to the currently accepted rate of non-response to therapy,
      implementation of this easily derived score could avoid a significant number of
      futile treatments. These findings should be validated in additional independent
      cohorts.

PMID- 30219889
TI  - Farm-Level Agricultural Biodiversity in the Peruvian Andes Is Associated with
      Greater Odds of Women Achieving a Minimally Diverse and Micronutrient Adequate
      Diet.
AB  - Background: The extent to and mechanisms by which agricultural biodiversity may
      influence diet diversity and quality among women are not well understood.
      Objectives: We aimed to 1) determine the association of farm-level agricultural
      biodiversity with diet diversity and quality among women of reproductive age in
      Peru and 2) determine the extent to which farm market orientation mediates or
      moderates this association. Methods: We surveyed 600 households with the use of
      stratified random sampling across 3 study landscapes in the Peruvian Andes with
      diverse agroecological and market conditions. Diet diversity and quality among
      women were assessed by using quantitative 24-h dietary recalls with repeat
      recalls among 100 randomly selected women. We calculated a 10-food group diet
      diversity score (DDS), the Minimum Dietary Diversity for Women (MDD-W) indicator,
      probability of adequacy (PA) of 9 micronutrients by using a measurement-error
      model approach, and mean PA (MPA; mean of PAs for all nutrients). Agricultural
      biodiversity was defined as a count of crop species cultivated by the household
      during the 2016-2017 agricultural season. Results: In regression analyses
      adjusting for sociodemographic and agricultural characteristics, farm-level
      agricultural biodiversity was associated with a higher DDS (incidence rate ratio
      from Poisson regression: 1.03; P < 0.05) and MPA (ordinary least-squares beta
      coefficient: 0.65; P < 0.1) and higher odds of achieving a minimally diverse diet
      (MDD-W: OR from logistic regression: 1.17; 95% CI: 1.11, 1.23) and a diet that
      met a minimum threshold for micronutrient adequacy (MPA >60%: OR: 1.21; 95% CI:
      1.10, 1.35). Farm market orientation did not consistently moderate these
      associations, and in path analyses we observed no consistent evidence of
      mediation of these associations by farm market orientation. Conclusions: Farm
      level agricultural biodiversity was associated with moderately more diverse and
      more micronutrient-adequate diets among Peruvian women. This association was
      consistent across farms with varying levels of market orientation, although
      agricultural biodiversity likely contributed to diets principally through
      subsistence consumption.

PMID- 30219890
TI  - Using Normalization Process Theory to Evaluate the Implementation of Montessori
      based Volunteer Visits Within a Canadian Long-term Care Home.
AB  - Background and Objectives: Montessori-based interventions (MBIs) have potential
      to improve the life quality of long-term care residents with dementia. In this
      study, we aimed to understand the processes by which staff integrated a volunteer
      led MBI into practice within a special dementia care unit, and to explore staff
      members ' perceptions of associated strengths and limitations. Research Design
      and Methods: This study relied on a qualitative descriptive design. Following a 3
      month period of volunteer involvement, we conducted 21 interviews with staff
      members to document perceptions of the new program and subjected interview
      transcripts to qualitative content analysis, guided by normalization process
      theory. Results: During the implementation of the volunteer-led MBI, staff
      members developed a shared understanding of the intervention, a sense of
      commitment, practical ways to support the intervention, and opinions about the
      value of the residents. Overall, we found that the volunteer-led MBI was quickly
      and successfully integrated into practice and was perceived to support both
      residents and staff members in meaningful ways. Nevertheless, some limitations
      were also identified. Discussion and Implications: Volunteer-delivered MBIs are a
      useful adjunct to practice within a special dementia care unit. This article
      raises attention to some strengths and limitations associated with this approach.

PMID- 30219891
TI  - The Presenteeism Scale as a measure of productivity loss.
AB  - Background: Work Ability Score (WAS) is a common instrument for assessing work
      ability but its validity in assessing presenteeism and productivity loss is
      unknown. Aims: To validate a WAS-based measure, the Presenteeism Scale (PS), and
      to evaluate its accuracy as a presenteeism instrument among forestry employees.
      Methods: This validation study was based on questions of perceived WAS assessed
      using the Work Ability-Personal Radar (WA-PR) instrument and on questions of
      perceived productivity loss and presenteeism assessed using a cross-sectional
      questionnaire survey. Pearson's correlation test was used to ascertain the
      associations between variables. The association of productivity loss with
      presenteeism was evaluated using a logistic regression model. The predictive
      ability of presenteeism was tested using the receiver-operating characteristic
      curve. Results: There were 339 respondents in the cross-sectional survey, 257 in
      the WA-PR and 107 respondents participating in both surveys. The prevalence of
      presenteeism was 48%. Presenteeism was significantly (P < 0.05) higher among
      those reporting productivity losses. Presenteeism is extremely accurate in
      predicting perceived productivity loss but less accurate in predicting PS-based
      productivity loss. The odds ratio (OR) of self-estimated productivity loss was 77
      times higher (OR 77.39, 95% confidence interval [CI] 25.36-236.12) among those
      with presenteeism. Correspondingly, OR of productivity loss based on the PS was
      three times higher (OR 3.05, 95% CI 1.16-8.04). Conclusions: The PS may be a
      valid tool for predicting productivity loss and may be as good as other
      instruments. However, further research is needed to improve its accuracy.

PMID- 30219892
TI  - Principals about principal components in statistical genetics.
AB  - Principal components (PCs) are widely used in statistics and refer to a
      relatively small number of uncorrelated variables derived from an initial pool of
      variables, while explaining as much of the total variance as possible. Also in
      statistical genetics, principal component analysis (PCA) is a popular technique.
      To achieve optimal results, a thorough understanding about the different
      implementations of PCA is required and their impact on study results, compared to
      alternative approaches. In this review, we focus on the possibilities,
      limitations and role of PCs in ancestry prediction, genome-wide association
      studies, rare variants analyses, imputation strategies, meta-analysis and
      epistasis detection. We also describe several variations of classic PCA that
      deserve increased attention in statistical genetics applications.

PMID- 30219893
TI  - Wolbachia both aids and hampers the performance of spider mites on different host
      plants.
AB  - In the last few decades, many studies have revealed the potential role of
      arthropod bacterial endosymbionts in shaping the host range of generalist
      herbivores and their performance on different host plants, which, in turn, might
      affect endosymbiont distribution in herbivore populations. We tested this by
      measuring the prevalence of endosymbionts in natural populations of the
      generalist spider mite Tetranychus urticae on different host plants. Focusing on
      Wolbachia, we then analysed how symbionts affected mite life-history traits on
      the same host plants in the laboratory. Overall, the prevalences of Cardinium and
      Rickettsia were low, whereas that of Wolbachia was high, with the highest values
      on bean and eggplant and the lowest on morning glory, tomato and zuchini.
      Although most mite life-history traits were affected by the plant species only,
      Wolbachia infection was detrimental for the egg-hatching rate on morning glory
      and zucchini, and led to a more female-biased sex ratio on morning glory and
      eggplant. These results suggest that endosymbionts may affect the host range of
      polyphagous herbivores, both by aiding and hampering their performance, depending
      on the host plant and on the life-history trait that affects performance the
      most. Conversely, endosymbiont spread may be facilitated or hindered by the
      plants on which infected herbivores occur.

PMID- 30219895
TI  - Commentary on: Enhancing Facelift With Simultaneous Submalar Implant
      Augmentation.

PMID- 30219896
TI  - Advanced Basal Cell Cancer: Concise Review of Molecular Characteristics and Novel
      Targeted and Immune Therapeutics.
AB  - Metastatic basal cell carcinoma is an ultra-rare manifestation of a common
      disease, appearing in 0.0028% to 0.5% of basal cell carcinomas. Initial
      therapeutic efforts focused on cytotoxic chemotherapy administration. However, it
      is now known that the Hedgehog signaling pathway is crucial for basal cell
      proliferation and Hedgehog pathway mutations may lead to tumorigenesis; thus,
      small molecule inhibitors of alterations in the components of this pathway,
      including smoothened (SMO) and GLI, have been the focus of recent therapeutic
      developments. Indeed, the European Medicines Agency (EMA) and the Food and Drug
      Administration (FDA) have approved the SMO inhibitors, vismodegib and sonidegib,
      with additional GLI inhibitors currently in clinical trials. Molecular profiling
      of these tumors has revealed other potential targets for therapy, including high
      tumor mutational burden and PD-L1 amplification, which predict response to immune
      checkpoint blockade (PD-1 and PD-L1 inhibitors). An illustrative patient with a
      giant, advanced, unresectable basal cell carcinoma who obtained an ongoing
      complete remission after treatment with a combination of an immune checkpoint
      inhibitor (due to the tumor's high mutational burden) and the Hedgehog inhibitor
      vismodegib is described. A fuller understanding of the genomic portfolio of these
      patients can assist in developing novel, rational therapeutic approaches that
      should continue to improve responses and outcomes.

PMID- 30219894
TI  - Role of ribosome assembly in Escherichia coli ribosomal RNA degradation.
AB  - DEAD-Box proteins (DBPs) constitute a prominent class of RNA remodeling factors
      that play a role in virtually all aspects of RNA metabolism. To better define
      their cellular functions, deletions in the genes encoding each of the Escherichia
      coli DBPs were combined with mutations in genes encoding different Ribonucleases
      (RNases). Significantly, double-deletion strains lacking Ribonuclease R (RNase R)
      and either the DeaD or SrmB DBP were found to display growth defects and an
      enhanced accumulation of ribosomal RNA (rRNA) fragments. As RNase R is known to
      play a key role in removing rRNA degradation products, these observations
      initially suggested that these two DBPs could be directly involved in the same
      process. However, additional investigations indicated that DeaD and SrmB
      dependent rRNA breakdown is caused by delays in ribosome assembly that increase
      the exposure of nascent RNAs to endonucleolytic cleavage. Consistent with this
      notion, mutations in factors known to be important for ribosome assembly also
      resulted in enhanced rRNA breakdown. Additionally, significant levels of rRNA
      breakdown products could be visualized in growing cells even in the absence of
      assembly defects. These findings reveal a hitherto unappreciated mechanism of
      rRNA degradation under conditions of both normal and abnormal ribosome assembly.

PMID- 30219897
TI  - Does probiotic consumption reduce antibiotic utilization for common acute
      infections? A systematic review and meta-analysis.
AB  - Background: Overall reduction of antibiotic use is a widely adopted public health
      goal. Given evidence that consuming probiotics reduce the incidence, duration
      and/or severity of certain types of common acute infections, we hypothesized that
      probiotics are associated with reduced antibiotic use. This systematic review of
      randomized controlled trials (RCTs) assessed the impact of probiotic
      supplementation (any strain, dose or duration), compared to placebo, on
      antibiotic utilization for common, acute infections in otherwise healthy people
      of all ages. Methods: We searched 13 electronic databases including MEDLINE,
      Embase and CENTRAL from inception to 17th January 2017. Backward and forward
      citation searches were also conducted. Two reviewers independently selected
      studies for inclusion and extracted study data. We assessed risk of bias for
      individual studies using criteria adapted from the Centre for Reviews and
      Dissemination, and the quality of evidence for each outcome was assessed using
      the GRADE system. Studies that evaluated similar outcomes were pooled
      statistically in meta-analyses using a random-effects model. Results: We screened
      1533 citations, and of these, 17 RCTs met our predefined inclusion criteria. All
      17 were conducted in infants and/or children with a primary aim of preventing
      acute respiratory tract infections, acute lower digestive tract infections or
      acute otitis media. Included studies used 13 probiotic formulations, all
      comprising single or combination Lactobacillus and Bifidobacterium delivered in a
      range of food or supplement products. Mean duration of probiotic supplementation
      ranged from 4 days to 9 months. Trial quality was variable. Meta-analysis
      demonstrated that infants and children who received probiotics to prevent acute
      illnesses had a lower risk of being prescribed antibiotics, relative to those who
      received placebo (Pooled Relative Risk = 0.71, 95% CI: 0.54-0.94). When
      restricted to five studies with a low risk of bias, the pooled relative risk was
      0.46 (95% CI: 0.23-0.97). Significant statistical heterogeneity was present in
      effect size estimates, which appeared to be due to one trial which could partly
      be considered as an outlier. Conclusions: Probiotics, provided to reduce the risk
      for common acute infections, may be associated with reduced antibiotic use in
      infants and children. Additional well-designed studies are needed to substantiate
      these findings in children and explore similar findings in other population
      groups.

PMID- 30219898
TI  - SlARF10, an auxin response factor, is involved in chlorophyll and sugar
      accumulation during tomato fruit development.
AB  - The photosynthesis of green tomatoes contributes to fruit growth and carbon
      economy. The tomato auxin response factor 10 (SlARF10) belongs to the ARF family
      and is located in nucleus. In this study, we found that SlARF10 was highly
      expressed in green fruit. Overexpression of SlARF10 in fruit produced a dark
      green phenotype whilst knock-down by RNAi produced a light-green phenotype.
      Autofluorescence and chlorophyll content analyses confirmed the phenotypes, which
      indicated that SlARF10 plays an important role in chlorophyll accumulation.
      Overexpression of SlARF10 positively affected photosynthesis in both leaves and
      fruit. Furthermore, SlARF10-overexpression lines displayed improved accumulation
      of starch, fructose, and sucrose in fruit, whilst SlARF10-RNAi lines showed
      decreased accumulation of starch and sucrose. Regulation of SlARF10 expression
      altered the expression of AGPase starch biosynthesis genes. SlARF10 positively
      regulated the expression of SlGLK1, POR, CBP1, and CBP2, which are related to
      chlorophyll metabolism and regulation. Electrophoretic mobility shift assays
      confirmed that SlARF10 directly targets to the SlGLK1 promoter. Our results thus
      indicate that SlARF10 is involved in chlorophyll accumulation by transcriptional
      activation of SlGLK1 expression in tomato fruit, and provide insights into the
      link between auxin signaling, chloroplast activity, and sugar metabolism during
      tomato fruit development.

PMID- 30219899
TI  - The 4q25 variant rs13143308T links risk of atrial fibrillation to defective
      calcium homeostasis.
AB  - Aims: Single nucleotide polymorphisms on chromosome 4q25 have been associated
      with risk of atrial fibrillation (AF) but the exiguous knowledge of the
      mechanistic links between these risk variants and underlying electrophysiological
      alterations hampers their clinical utility. Here, we here tested the hypothesis
      that 4q25 risk variants cause alterations in the intracellular calcium
      homeostasis that predispose to spontaneous electrical activity. Methods and
      results: Western blotting, confocal calcium imaging, and patch-clamp techniques
      were used to identify mechanisms linking the 4q25 risk variants rs2200733T and
      rs13143308T to defects in the calcium homeostasis in human atrial myocytes. Our
      findings revealed that the rs13143308T variant was more frequent in patients with
      AF and that myocytes from carriers of this variant had a significantly higher
      density of calcium sparks (14.1+/-4.5 vs. 3.1+/-1.3 events/min, p = 0.02),
      frequency of transient inward (ITI) currents (1.33+/-0.24 vs. 0.26+/-0.09
      events/min, p < 0.001) and incidence of spontaneous membrane depolarizations
      (1.22+/-0.26 vs. 0.56+/-0.17 events/min, p = 0.001) than myocytes from patients
      with the normal rs13143308G variant. These alterations were linked to higher
      sarcoplasmic reticulum calcium loading (10.2+/-1.4 vs. 7.3+/-0.5amol/pF, p =
      0.01), SERCA2 expression (1.37+/-0.13 fold, p = 0.03) and RyR2 phosphorylation at
      s2808 (0.67+/-0.08 vs. 0.47+/-0.03, p = 0.01) but not at s2814 (0.28+/-0.14 vs.
      0.31+/-0.14, p = 0.61) in patients carrying the rs13143308T risk variant.
      Furthermore, the presence of a risk variant or AF independently increased the ITI
      frequency and the increase in the ITI frequency observed in carriers of the risk
      variants was exacerbated in those with AF. By contrast, the presence of a risk
      variant did not affect the amplitude or properties of the L-type calcium current
      in patients with or without AF. Conclusions: We here identify the 4q25 variant
      rs13143308T as a genetic risk marker for AF, specifically associated with
      excessive calcium release and spontaneous electrical activity linked to increased
      SERCA2 expression and RyR2 phosphorylation.

PMID- 30219900
TI  - Perinatal outcomes of singleton live births with and without vanishing twin
      following transfer of multiple embryos: analysis of 113 784 singleton live
      births.
AB  - STUDY QUESTION: Does transfer of multiple embryos affect perinatal outcomes of
      resulting singleton live births following ART? SUMMARY ANSWER: There is a higher
      risk of preterm birth (PTB) and low birthweight (LBW) in singleton live births
      associated with spontaneous reduction of an initial multiple to singleton
      gestation following transfer of multiple embryos. WHAT IS KNOWN ALREADY:
      Singleton pregnancies following ART are at a higher risk of adverse perinatal
      outcomes compared to spontaneous conceptions. Earlier studies have found an
      increased risk of PTB and LBW in singletons following transfer of multiple
      embryos versus single embryo transfer (SET). However, these studies did not
      address the specific role of vanishing twin, i.e. spontaneous reduction of an
      initial multiple to singleton gestation. STUDY DESIGN, SIZE, DURATION: Anonymised
      data on all ART cycles performed in the UK were obtained from the Human
      Fertilization and Embryology Authority. Data from 1991 to 2011 involving 508 410
      fresh and 131 157 frozen autologous ART cycles resulting in 95 779 and 18 005
      singleton live births, respectively, were analyzed. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Fresh and frozen ART cycles were analyzed separately to compare
      perinatal outcomes of PTB and LBW of singleton live births resulting from
      transfer of multiple (>=2) embryos versus SET. Logistic regression analysis was
      performed adjusting for confounders. Subgroup analyses were carried out for
      perinatal outcomes of singleton live births with initial multiple or initial
      single gestational sacs following transfer of multiple embryos versus singleton
      live births following SET. MAIN RESULTS AND THE ROLE OF CHANCE: In fresh cycles,
      there was a significantly higher risk of PTB (adjusted odds ratio (aOR) 2.70, CI
      2.37-3.05) and LBW (aOR 2.76, CI 2.44-3.13) in singleton live births with initial
      multiple gestational sacs but there was no significant difference in the risk of
      PTB (aOR 1.08, CI 1.00-1.16) or LBW (aOR 1.08, CI 1.00-1.16) in singleton live
      births with an initial single gestational sac following transfer of >=2 embryos
      compared to those following SET. In frozen cycles, there was a significantly
      higher risk of PTB (aOR 2.13, CI: 1.55-2.93) and LBW (aOR 2.61, CI: 1.87-3.64) in
      singleton live births with initial multiple gestational sacs but there was no
      significant difference in the risk of PTB (aOR 1.02, CI: 0.88-1.18) or LBW (aOR
      0.91, CI: 0.77-1.07) in the singleton live births with an initial single
      gestational sac following transfer of >=2 embryos compared to those following
      SET. LIMITATIONS, REASONS FOR CAUTION: While the analysis was adjusted for a
      number of known confounders, the dataset had no information for confounders such
      as smoking, BMI, previous obstetric history and comorbid medical conditions
      during pregnancy. The lack of information about the timing of occurrence of the
      vanishing phenomenon is another limitation because poorer perinatal outcomes of a
      surviving twin have been reported following second trimester fetal demise
      compared to the first trimester. WIDER IMPLICATIONS OF THE FINDINGS: The study
      results suggest that the vanishing twin phenomenon is associated with increased
      risk of PTB and LBW in the resulting singleton live births and there was no
      increased risk when there was a single gestational sac from the outset following
      transfer of multiple embryos. STUDY FUNDING/COMPETING INTERESTS: Nil.

PMID- 30219901
TI  - Obesity paradox in ST-elevation myocardial infarction: Is it all about infarct
      size?

PMID- 30219902
TI  - The associations between physical activity, including physical activity
      intensity, and fear of falling differs by fear severity in older adults living in
      the community.
AB  - Objectives: Fear of falling (FoF) is common in older adults. Physical activity
      decreases as FoF increases. However, this association between physical activity
      and FoF may vary depending on activity intensity. The current study was performed
      to explore the associations between FoF and step count, light-intensity physical
      activity (LPA), and moderate/vigorous-intensity physical activity (MVPA), in
      community-dwelling older adults. Methods: This cross-sectional observational
      study was held at a local community association center, with 242 older adults
      living independently in the community (mean age: 75.1 5.4 years). FoF was defined
      using the Falls Efficacy Scale-International and categorized into three levels
      (low, moderate, and high). Physical activity was measured using a uniaxial
      accelerometer worn for 7 consecutive days, and by calculating daily step count,
      LPA, and MVPA, over this period. Results: Step count and physical activity
      intensity showed significant linear trends across FoF severity (p < 0.01,
      respectively). High FoF decreased step count by approximately 2000 steps/day.
      Further, high FoF was significantly associated with short durations of both LPA
      and MVPA. Additionally, moderate FoF was associated with decreased LPA duration,
      even after adjustment for confounding variables. Discussions: Physical activity
      decreased concomitantly with a rise in FoF severity. Moreover, the association
      between physical activity and FoF differed by physical activity intensity level
      in community-dwelling older adults. Further studies are needed to investigate the
      causal relationship between FoF and objective physical activity in this
      population.

PMID- 30219903
TI  - Letter to the Editor: "Association of Vitamin D Deficiency With Peripheral
      Arterial Disease: A Meta-Analysis of Literature Studies".

PMID- 30219904
TI  - Comparative study of two commercial tests for Strongyloides stercoralis serologic
      diagnosis.
AB  - Background: Serological diagnosis of Strongyloides stercoralis is often limited
      by its low specificity due to cross-reactivity with other parasitic nematodes.
      Novel serological tests assumed to be more specific have been recently developed.
      The aim of our study was to compare two commercial tests based on different
      antigens for S. stercoralis diagnosis in humans from a non-endemic area. Methods:
      A retrospective laboratory-based study was conducted in the Hospital
      Universitario 12 de Octubre, Madrid, Spain. Samples from patients with a
      requested S. stercoralis serology from January 2013 to October 2016 were tested
      with two commercial enzyme-linked immunosorbent assay (ELISA) tests (crude larval
      suspension ELISA [CrAg-ELISA] and recombinant antigen ELISA [NIE-ELISA]).
      Sensitivity, specificity and predictive values were calculated using primary and
      composite gold standards. The kappa index was calculated. Results: A total of 249
      samples from 233 patients were tested (kappa=0.735). The CrAg-ELISA yielded
      sensitivities from 89.2% (95% confidence interval [CI] 80.7 to 94.2) to 94.7%
      (95% CI 75.4 to 99.0) and the NIE-ELISA from 72.3% (95% CI 58.2 to 83.1) to 78.9%
      (95% CI 56.7 to 91.5). Specificity ranged from 72.3% (95% CI 58.2 to 83.1) to
      89.3% (95% CI 83.1 to 93.4) for the CrAg-ELISA and from 85.1% (95% CI 72.3 to
      92.6) to 93.6% (95% CI 88.2 to 96.6) for the NIE-ELISA. Conclusions: The NIE
      ELISA is more specific than the CrAg-ELISA, but its low sensitivity limits its
      use in S. stercoralis screening. New diagnostic tests are needed for the
      diagnosis of S. stercoralis.

PMID- 30219905
TI  - Insight Into the Salivary Secretome of Varroa destructor and Salivary Toxicity to
      Apis cerana.
AB  - The Varroa destructor (Acari Varroidae) mite is a serious threat to honey bee due
      to hemolymph feeding and virus transmission. Mite salivary proteins are involved
      in these interactions. However, the salivary secretome has not been previously
      characterized. In this paper, the saliva of V. destructor was found to be toxic
      to the worker larvae of Apis cerana (Hymenoptera Apidae) in the absence of
      deformed wing virus (DWV) and to stimulate the development of deformed wings in
      Apis mellifera (Hymenoptera Apidae) adults in the presence of DWV. The salivary
      secretome was analyzed by nano-liquid chromatography coupled to tandem mass
      spectrometry (nano-LC-MS/MS). A search of the resulting data against peptide
      databases using the software Mascot yielded 356, 53, and 9 matched proteins from
      V. destructor, A. mellifera, and DWV, respectively. The saliva contained Varroa
      mite proteins identified as important for potential virulence to A. cerana
      larvae, for the inhibition of harmful microorganisms, for the utilization of bee
      nutrients, and for antioxidant, oxidation-reduction and detoxification functions
      as well as A. mellifera proteins identified as nutrients important for mite
      reproduction. The saliva proteins also contained viral proteins from one virus,
      DWV. These results provide a strong foundation for understanding the interactions
      among the Varroa mite, honeybee, and DWV.

PMID- 30219906
TI  - Rasch Analysis and Construct Validity of the Disease Burden Morbidity Assessment
      in Older Adults.
AB  - Purpose of the Study: The Disease Burden Morbidity Assessment (DBMA) is a self
      report questionnaire in which participants rate the disease burden caused by a
      number of medical conditions. This paper studies the measurement properties of
      the DBMA, using Rasch analysis. Design and Methods: We used data of 1,400
      community-dwelling adults aged 50 years and older participating in the Ageing in
      Spain Longitudinal Study, Pilot Survey (ELES-PS). Test of fit to the Rasch model,
      reliability, unidimensionality, response dependency, category structure, scale
      targeting, and differential item functioning (DIF) were studied in an iterative
      way. Construct validity of the linear measure provided by the Rasch analysis was
      subsequently assessed. Results: To achieve an adequate fit to the Rasch model,
      all items were rescored by collapsing response categories. Reliability (Person
      Separation Index) was low. The scale was unidimensional and neither response
      dependency nor relevant DIF were found. The linear measure had a correlation of 
      0.48 with physical functioning, -0.47 with perceived health, 0.32 with
      depression, and -0.24 with quality of life (QoL) and displayed satisfactory known
      groups validity by sex and age groups. Relative precision analysis showed that
      the linear measure discriminated better between age groups than the original raw
      score, but for sex no difference was found. Implications: Despite some
      limitations, support was found for the validity of the DBMA in older adults. Its
      linear scores may be useful to assess strategies aimed at improving the QoL of
      patients with multimorbidity. More research is needed in a hospital-based sample.

PMID- 30219907
TI  - An interview with Professor Martin Matzuk.

PMID- 30219909
TI  - FA01.01: MINIMALLY INVASIVE APPROACH RESULTS IN BETTER OUTCOME COMPARED TO OPEN
      ESOPHAGECTOMY-A PROPENSITY SCORE MATCHED ANALYSIS.
AB  - Background: Esophagectomy remains the mainstay treatment for esophageal cancer.
      Minimally invasive techniques have gained popularity in recent years. Whether
      minimally invasive methods result in equivalent or superior outcome to open
      esophagectomy or not is still controversial. The aim of the current study is to
      compare outcomes of minimally invasive and open esophagectomy from a single
      institution, using propensity score matching to lessen biases. Methods: From 1994
      2016, 724 patients with squamous cell cancer of the esophagus who underwent
      esophagectomy were studied. Data were retrieved from a prospectively collected
      database. Patients were divided into two groups: 453 had open esophagectomy (open
      group), and 271 had VATS esophagectomy with gastric mobilization either via
      laparotomy or laparoscopically (MIE group). A propensity score was generated for
      each patient based on age, gender, tumor level, use of neoadjuvant therapy,
      American Society of Anaesthesiologists (ASA) score, pathologic stage of disease,
      site of anastomosis, and residual tumour (R) categories and the two matched
      groups were compared in clinico-pathological features, morbidity and mortality
      rates, and long-term survival. All statistical calculations were performed with
      SPSS version 24 (SPSS, Chicago, IL). Results: A total of 158 patients in MIE and
      187 in open group are matched for comparison (1:3 matching). MIE resulted in less
      blood loss (220 vs 400ml, P < 0.001) but longer operative time (461 vs 305 mins,
      P < 0.001). Wound infection (3.7% vs 10.7%, P = 0.01) and respiratory
      complications (29% vs 55.1%, P < 0.001) were also less in MIE group. Except for a
      higher rate of conduit ischemia (6.3% vs 1.6%, P = 0.02), MIE had comparable
      surgical outcomes with open technique in rates of anastomotic leakage (5.7% vs
      5.3%, P = 0.89), recurrent laryngeal nerve palsy (20.1% vs 18.7%, P = 0.10),
      reoperation (10.8% vs 8.6%, P = 0.49), and length of postoperative hospital stay
      (13 vs 14 days, P = 0.50). Lymph node harvest was significantly higher with MIE
      (35 vs 21, P < 0.001), a longer median survival was also evident compared to the
      open group (42.3 vs 24.7 months, P = 0.03). Conclusion: Although requiring longer
      operative time, MIE led to less wound and respiratory complications without
      jeopardizing surgical and oncological outcome. The more comprehensive
      lymphadenectomy could potentially improve prognosis. Disclosure: All authors have
      declared no conflicts of interest.

PMID- 30219912
TI  - Erratum to: "Enhanced Recovery After SurgeryTM Awake Minimally-Invasive
      Transforaminal Lumbar Interbody Fusion: 2-Dimensional Operative Video" by Hsuan
      Kan Chang et al. Operative Neurosurgery 2018; doi: 10.1093/ons/opy187.

PMID- 30219911
TI  - FA01.03: USE OF 'NON-TUBE NO FASTING' ERAS PROTOCOL IN PATIENTS AFTER MIE WITH
      LI'S ANASTOMOSIS: OUTCOMES IN THE FIRST 113 PATIENTS PERFORMED BY A SURGEON AFTER
      TRAINING COURSE.
AB  - Background: Use of enhanced recovery after surgery(ERAS) protocol in the patients
      after esophagectomy is reported to be feasible and safe in recent studies. And in
      Prof. Yin Li's research, patients after minimally invasive esophagectomy(MIE)
      with Li's anastomosis took oral feeding on the 1st day after operation (POD1).
      However, all the esophagectomy-procedures were proceeded by experienced experts.
      There was no report regarding whether ERAS protocol after MIE with Li's
      anastomosis could be safely proceeded by a young surgeon after training course.
      The aim of this study was to evaluate the feasibility and safety of 'Non-Tube No
      Fasting' ERAS Protocol in patients after MIE with Li's Anastomosis proceeded by a
      surgeon after the training course. Methods: We retrospectively reviewed the
      clinical data of patients who underwent MIE for cancer from December 2015 to
      September 2017 by a new surgical team finished MIE training course in our
      department. During the study period, the new team performed Mckeown MIE with Li's
      anastomosis for 127 esophageal cancer patients. We analyzed the data of 113
      patients who followed the protocol of 'Non-tube No Fasting' ERAS. The primary end
      points were the incidence of anastomotic fistula, the injury of recurrent
      laryngeal nerve, pneumonia, and postoperative length of hospital-stay. Results:
      All the 113 patients began oral feeding on POD1. Two patients exited the ERAS
      protocol on account of bucking caused by recurrent laryngeal nerve injury on
      POD3. The incidence of anastomotic fistula, recurrent laryngeal nerve injury and
      pneumonia were 3.5% (4/113), 12.4%(14/113) and 18.5%(21/113). The average length
      of postoperative hospital-stay was 8.6 +/- 6.9 days. Both of the in-hospital
      mortality and 30-day mortality were 0. Conclusion: Our date indicated that it was
      feasible and safe for a selected surgeon after 'Non-tube no fasting' ERAS and MIE
      training courses to proceed the protocol. Of course, more clinical researches are
      needed to confirm this result. Disclosure: All authors have declared no conflicts
      of interest.

PMID- 30219910
TI  - FA01.02: THE EFFECT OF POSTOPERATIVE COMPLICATIONS AFTER MIE ON LONG-TERM
      SURVIVAL: A RETROSPECTIVE, MULTI-CENTER COHORT STUDY.
AB  - Background: Esophagectomy has a high incidence of postoperative morbidity.
      Complications lead to a decreased short-term survival, however the influence of
      those complications on long-term survival is still unclear. Most of the performed
      studies are small, single center cohort series with inconclusive or conflicting
      results. Minimally invasive esophagectomy (MIE) has been shown to be associated
      with a reduced postoperative morbidity. In this study, the influence of
      complications on long-term survival for patients with esophageal cancer
      undergoing a MIE were investigated. Methods: Data was collected from the
      EsoBenchmark database, a collaboration of 13 high-volume centers routinely
      performing MIE. Patients were included in this database from June 1, 2011 until
      May 31, 2016. Complications were scored according to the Clavien-Dindo (CD)
      classification for surgical complications. Major complications were defined as a
      CD grade >= 3. The data were corrected for 90-day mortality to correct for the
      short-term effect of postoperative complications on mortality. Overall survival
      was analyzed using the Kaplan Meier, log rank- and (uni- and multivariable) Cox
      regression analyses. Results: A total of 926 patients were eligible for analysis.
      Mean follow-up time was 30.8 months (SD 17.9). Complications occurred in 543
      patients (59.2%) of which 39.3% had a major complication. Anastomotic leakage
      (AL) occurred in 135 patients (14.5%) of which 9.2% needed an intervention (CD
      grade >= 3). A significant worse long-term survival was observed in patients with
      any AL (HR 1.73, 95% CI 1.29-2.32, P < 0.001) and for patients with AL CD grade
      >=3 (HR 1.86, 95% CI 1.32-2.63, P < 0.001). Major cardiac complications occurred
      in 18 patients (1.9%) and were related to a decreased long-term survival (HR
      2.72, 95% CI 1.38-5.35, p 0.004). For all other complications, no significant
      influence on long-term survival was found. Conclusion: The occurrence and
      severity of anastomotic leakage and cardiac complications after MIE negatively
      affect long-term survival of esophageal cancer patients. Disclosure: All authors
      have declared no conflicts of interest.

PMID- 30219913
TI  - Impaired Odor Perception in Autism Spectrum Disorder Is Associated with Decreased
      Activity in Olfactory Cortex.
AB  - Autism Spectrum Disorders (ASDs) are characterized by atypical sensory
      functioning in the visual, tactile, and auditory systems. Although less explored,
      olfactory changes have been reported in ASD patients. To explore these changes on
      a neural level, 18 adults with ASD and 18 healthy neurotypical controls were
      examined in a 2-phase study. Participants were first tested for odor threshold
      and odor identification. Then, (i) structural magnetic resonance (MR) images of
      the olfactory bulb were acquired, and (ii) a functional MR imaging olfaction
      study was conducted. ASD patients exhibited decreased function for odor
      thresholds and odor identification; this was accompanied by a relatively
      decreased activation in the piriform cortex. In conclusion, these findings
      suggest, that the known alterations in olfaction in ASD are rooted in the primary
      olfactory cortex.

PMID- 30219914
TI  - Emerging impacts of biological methylation on genetic information.
AB  - The central dogma of molecular biology explains the fundamental flow of genetic
      information for life. Although genome sequence (DNA) itself is a static chemical
      signature, it includes multiple layers of information composed of messenger RNA
      (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and small RNAs, all of which
      are involved in protein synthesis, and is passing from parents to offspring via
      DNA. Methylation is a biologically important modification, because DNA, RNAs, and
      proteins, components of the central dogma, are methylated by a set of
      methyltransferases. Recent works focused on understanding a variety of biological
      methylation have shed light on new regulation of cellular functions. In this
      review, we briefly discuss some of those recent findings of methylation,
      including DNA, RNAs, and proteins.

PMID- 30219916
TI  - Improving access to appropriate post-exposure doxycycline for Lyme disease
      prophylaxis: role for community pharmacies.
AB  - The transmission of Borrelia burgdorferi to humans through tick bites results in
      Lyme disease. Appropriate therapy for Lyme disease is antibacterial drugs, most
      often doxycycline. Patients often approach community pharmacists for self-care
      assistance with the symptoms of Lyme disease: fever, headache, fatigue and skin
      rash. Pharmacists with the patient history are trained and capable of
      appropriately dispensing doxycycline to treat these patients and prevent the
      spread of infection to the joints, nerves or heart. We challenge restrictions to
      the appropriate and timely provision of therapy for Lyme disease and encourage
      the use of community pharmacists in managing these patients.

PMID- 30219915
TI  - Safety and Clinical Activity of Atezolizumab in Head and Neck Cancer: Results
      From a Phase I Trial.
AB  - Background: Head and neck cancer (HNC) has a poor prognosis at advanced stages.
      Given the immunosuppressive tumor microenvironment in HNC, inhibition of the
      programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling pathway
      represents a promising therapeutic approach. Atezolizumab (anti-PD-L1) is
      efficacious against many tumor types. Here we report the clinical safety and
      activity from the HNC cohort of the phase Ia PCD4989g clinical trial. Patients
      and methods: Patients with previously-treated, advanced HNC received atezolizumab
      intravenously every 3 weeks for 16 cycles, up to 1 year or until loss of clinical
      benefit. Patients were monitored for safety and tolerability, and evaluated for
      response at least every 6 weeks. Baseline PD-L1 expression level and human
      papillomavirus (HPV) status were evaluated. Results: Thirty-two patients were
      enrolled; 7 patients (22%) had a primary tumor in the oral cavity, 18 (56%) in
      the oropharynx, 1 (3%) in the hypopharynx, 2 (6%) in the larynx, and 4 (13%) in
      the nasopharynx. Seventeen patients (53%) had >=2 prior lines of therapy. Twenty
      one patients (66%) experienced a treatment-related adverse event (TRAE), with 3
      experiencing grade 3 TRAEs and 1 experiencing a grade 4 TRAE. No grade 5 TRAEs
      were reported. Objective responses by Response Evaluation Criteria In Solid
      Tumors version 1.1 (RECIST v1.1) occurred in 22% of patients, with a median
      duration of response of 7.4 months (range 2.8-45.8 months). Progression-free
      survival was 2.6 months (range 0.5-48.4 months), and median overall survival was
      6.0 months (range 0.5-51.6+ months). Responses showed no association with HPV
      status or PD-L1 expression level. Conclusions: In this heavily pre-treated
      advanced HNC cohort, atezolizumab had a tolerable safety profile and encouraging
      activity, with responses observed regardless of HPV status and PD-L1 expression
      level. These findings warrant further investigation of atezolizumab in HNC.
      ClinicalTrials.gov number: NCT01375842.

PMID- 30219918
TI  - Leaf shedding increases the photosynthetic rate of the canopy in N2-fixing and
      non-N2-fixing woody species.
AB  - It has long been hypothesized that timing of leaf shedding is critical for plant
      fitness but there is little experimental evidence to support the hypothesis.
      According to an optimality theory, shedding of old leaves increases canopy
      photosynthesis despite some nitrogen (N) being lost as litterfall, when the ratio
      of daily photosynthesis to leaf N (N-use efficiency, epsilon) in old leaves,
      expressed as a fraction of epsilon in new leaves, becomes lower than the fraction
      of leaf N that is resorbed before shedding (RN). This was shown to be true for N
      poor plants but not for N-rich plants in a pot experiment; however, the use of
      planting pots imposes a variety of physical, chemical and biological constraints
      that could change the experimental results. Here we conducted a 3-year field
      survey in a cool temperate deciduous forest to examine whether Alnus sieboldiana
      Matsum. (N2-fixing) and Carpinus tschonoskii Maxim. (non-N2-fixing) shed their
      leaves to increase canopy photosynthesis in accord with the above criterion.
      These species often grow sympatrically and were chosen as representatives of N
      rich and N-poor plants, respectively. Overall, daily photosynthesis decreased
      with leaf age, accompanied by small changes in leaf N, resulting in a decrease in
      epsilon. In both species, epsilon of leaves at shedding expressed as a fraction
      of epsilon in new leaves was nearly equal to RN in all years, implying that the
      old leaves were shed to increase canopy photosynthesis. Our results, together
      with those of previous field surveys, suggested that the timing of leaf shedding
      is explained by N use in maximizing canopy photosynthesis across broad groups of
      species.

PMID- 30219917
TI  - Abiraterone Acetate for Cushing Syndrome: Study in a Canine Primary
      Adrenocortical Cell Culture Model.
AB  - Abiraterone acetate (AA) is a potent inhibitor of steroidogenic enzyme 17alpha
      hydroxylase/17,20-lyase (CYP17A1). AA is approved for the treatment of prostate
      cancer but could also be used to treat patients with Cushing syndrome (CS).
      Similar to humans, canine glucocorticoid synthesis requires CYP17A1, providing a
      useful animal model. The objective of this study was to preclinically investigate
      the effect of AA on adrenocortical hormone production, cell viability, and mRNA
      expression of steroidogenic enzymes in canine primary adrenocortical cell
      cultures (n = 9) from the adrenal glands of nine healthy dogs. The cells were
      incubated with AA (0.125 nM to 10 MUM) for 72 hours under basal conditions and
      with 100 nM ACTH(1-24). Adrenocortical hormone concentrations were measured in
      culture medium using liquid chromatography-mass spectrometry, RNA was isolated
      from cells for subsequent real-time quantitative PCR analysis, and cell viability
      was assessed with an alamarBlueTM assay. AA reduced cortisol (IC50, 21.4 +/- 4.6
      nM) without affecting aldosterone under basal and ACTH-stimulated conditions. AA
      increased progesterone under basal and ACTH-stimulated conditions but reduced
      corticosterone under basal conditions, suggesting concurrent inhibition of 21
      hydroxylation. AA did not affect the mRNA expression of steroidogenic enzymes and
      did not inhibit cell viability. In summary, primary canine adrenocortical cell
      culture is a useful model system for drug testing. For the treatment of CS, AA
      may to be superior to other steroidogenesis inhibitors due to its low toxicity.
      For future in vivo studies, dogs with endogenous CS may provide a useful animal
      model.

PMID- 30219919
TI  - Spousal loss and change in cognitive functioning: An examination of temporal
      patterns and gender differences.
AB  - Objectives: The study investigates whether the disadvantaged position of men in
      the adverse consequences of widowhood for health and mortality also exists for
      changes in cognitive health. Methods: We used data of up to 1,269 men and women
      aged 65 years and older who participated in the Longitudinal Aging Study
      Amsterdam in three-yearly assessments between 1992 and 2012 (5,123 person
      observations). All were married and without cognitive impairment (MMSE >= 24) at
      baseline and up to 419 lost their spouse. In fixed effects regression models, the
      effect of spousal loss on change in four domains of cognitive functioning was
      estimated independently of age-related cognitive change. Results: For women, a
      robust temporary decrease was found in the second year after spousal loss in the
      reasoning domain, but not in global cognitive functioning, processing speed, or
      memory. No robust effects were found for men. Discussion: Considering that only
      one cognitive domain was affected and effects were temporary, cognitive
      functioning seems rather robust to the experience of spousal loss. Despite men
      having often been reported to be in a disadvantaged position in other health
      domains, our analyses indicate no such pattern for cognitive functioning.

PMID- 30219921
TI  - Accelerating Soybean Breeding in a CO2-Supplemented Growth Chamber.
AB  - Soybean (Glycine max) is the most important dicot crop worldwide, and is
      increasingly used as a model legume due to the wide availability of genomic
      soybean resources; however, the slow generation times of soybean plants are
      currently a major hindrance to research. Here, we demonstrate a method for
      accelerating soybean breeding in compact growth chambers, which greatly shortens
      the generation time of the plants and accelerates breeding and research projects.
      Our breeding method utilizes commonly used fluorescent lamps (220 umol m-2 s-1 at
      the canopy level), a 14-h light (30  degrees C)/10-h dark (25  degrees C) cycle,
      and carbon dioxide (CO2) supplementation over 400 ppm. Using this approach, the
      generation time of the best-characterized elite Japanese soybean cultivar, Enrei,
      was shortened from 102-132 reported in the field to just 70 days, thereby
      allowing up to 5 generations per year instead of the 1-2 generations currently
      possible in the field and/or greenhouse. The method also facilitates the highly
      efficient and controlled crossing of soybean plants. Our method uses CO2
      supplementation to promote the growth and yield of plants, appropriate light and
      temperature conditions to reduce the days to flowering, and the reaping and
      sowing of immature seeds to greatly shorten the reproductive period. Thus, the
      appropriate parameters enable to accelerate soybean breeding in the compact
      growth chambers commonly used for laboratory research. The parameters used in our
      method could therefore be optimized for other species, cultivars, accessions, and
      experimental designs to facilitate rapid breeding in a wide range of crops.

PMID- 30219920
TI  - Safety outcomes during pediatric GH therapy: final results from the prospective
      GeNeSIS observational program.
AB  - Context: Safety concerns regarding premature mortality, diabetes, neoplasia and
      cerebrovascular disease in association with growth hormone (GH) therapy have been
      raised. Objective: To assess incidence of key safety outcomes. Design:
      Prospective, multinational, observational study (1999-2015). Setting: 22,311 GH
      treated children from 827 investigative sites in 30 countries. Patients: Children
      with growth disorders. Interventions: GH treatment. Main outcome measures:
      Standardized mortality (SMR) and incidence (SIR) ratios with 95% confidence
      intervals (CI) for mortality, diabetes, and primary cancer, using general
      population registries. Results: Predominant short stature diagnoses were GH
      deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with
      mean+/-SD follow-up of 4.2+/-3.2 years (~92,000 person-years [PY]). Forty-two
      deaths occurred in patients with follow-up, with SMR (95% CI) of 0.61 (0.44
      0.82); the SMR was elevated for patients with cancer-related organic GH
      deficiency (5.87 [3.21-9.85]). Based on 18 cases, Type 2 diabetes (T2DM) risk was
      elevated (SIR 3.77 [2.24-5.96]), but 72% had risk factors. In patients without
      cancer history, 14 primary cancers were observed (SIR 0.71 [0.39-1.20]). Second
      neoplasms occurred in 31/622 (5.0%) cancer survivors (10.7 [7.5-15.2] cases/1000
      PY), and intracranial tumor recurrences in 67/823 (8.1%) tumor survivors (16.9
      [13.3-21.5] cases/1000 PY). All 3 hemorrhagic stroke cases had risk factors.
      Conclusions: GeNeSIS data support the favourable safety profile of pediatric GH
      treatment. Overall risk for death or primary cancer was not elevated in GH
      treated children, and no hemorrhagic strokes occurred in patients without risk
      factors. T2DM incidence was elevated compared to the general population, but most
      cases had diabetes risk factors.

PMID- 30219922
TI  - General practitioners' attitudes and decision making regarding admission for
      older adults with infection: a UK qualitative interview study.
AB  - Background: The world has an ageing population. Infection is common in older
      adults; serious infection has a high mortality rate and is associated with
      unplanned admissions. In the UK, general practitioners (GPs) must identify which
      older patients require admission to hospital and provide appropriate care and
      support for those staying at home. Objectives: To explore attitudes of UK GPs
      towards referring older patients with suspected infection to hospital, how they
      weigh up the decision to admit against the alternatives and how alternatives to
      admission could be made more effective. Methods. Qualitative study using semi
      structured interviews. GPs were purposively sampled from across the UK to achieve
      maximum variation in terms of GP role, experience and practice population.
      Interview transcripts were coded and analysed using a modified framework
      approach. Results: GPs' key influences on decision making were grouped into
      patient, GP and system factors. Patient factors included clinical factors, social
      factors and shared decision making. GP factors included gut instinct, risk
      management and acknowledging an associated personal emotional burden. System
      factors involved weighing up the pressure on secondary care beds against
      increasing GP workload. GPs described that finding an alternative to admission
      could be more time consuming, complex to arrange or were restricted by lack of
      capacity. Conclusion: GPs need to be empowered to make safe decisions about place
      of care for older adults with suspected infection. This may mean developing
      strategies to support decision making as well as improving the ease of access to,
      and capacity of, any alternatives to admission.

PMID- 30219923
TI  - A generic individual-based model can predict yield, nitrogen content, and species
      abundance in experimental grassland communities.
AB  - The performance of an individual-based model accounting for the dynamics of
      forage legumes in multi-species grasslands was assessed. Morphogenetic shoot and
      root parameters were calibrated for seven widely-used species. Other model
      parameters, which concerned C and N metabolism, were obtained from the
      literature. The model was evaluated using a series of independent experiments
      combining the seven species in binary mixtures subject to regular defoliation.For
      all the species, the model could accurately simulate phytomer demography, leaf
      area dynamics, and root growth under conditions of weak competition. In addition,
      the plastic changes induced by competition for light and N in terms of plant
      development, leaf area, N uptake and total plant biomass were correctly
      anticipated. The different species displayed contrasting sensitivities to
      defoliation. The model was able to anticipate the superior ability of creeping
      species to sustain regular defoliation. As a result of competition and
      management, the balance between species changed over time and was strongly
      dependent on the pair of species used. The model proved able to capture these
      differences of community dynamics.Overall, the study demonstrated that
      integrating the individual components of population dynamics in a process-based
      model could provide good predictive capacity regarding mixtures of cultivated
      species.

PMID- 30219924
TI  - Intensive perioperative rehabilitation improves surgical outcomes after
      pancreaticoduodenectomy.
AB  - PURPOSE: Although the mortality rate for pancreaticoduodenectomy (PD) has
      decreased to around 2.8-5% in high-volume centers, postoperative complications
      are still common in 30-50% of cases. Preoperative exercise, called
      "prehabilitation," has been recently reported to reduce the frequency of
      complications after surgery. This study aims to evaluate the impact of the
      intensive perioperative rehabilitation on improvement of surgical outcomes for
      patients undergoing PD. METHODS: Between 2003 and 2014, 576 consecutive patients
      underwent PD in Wakayama Medical University Hospital. Of these, 331 patients
      received perioperative rehabilitation combined with prehabilitation and
      postoperative rehabilitation between 2009 and 2014. Previously, 245 patients
      underwent PD without perioperative rehabilitation between 2003 and 2008. We
      compared surgical outcomes between the patients undergoing PD with and without
      perioperative rehabilitation to evaluate the efficacy of our rehabilitation
      program. RESULTS: The frequency of pulmonary complications was significantly
      lower in patients undergoing PD with perioperative rehabilitation than those
      without (0.9% vs. 4.3%, P = 0.011). There were no significant differences in
      other complication or mortality rates. Length of hospital stay was also shorter
      in patients receiving perioperative rehabilitation than that of those not
      receiving it (16 vs. 24 days, P < 0.001). CONCLUSIONS: Intensive perioperative
      rehabilitation might reduce postoperative pulmonary complications and shorten
      postoperative hospital stay after PD. Therefore, we suggest that perioperative
      rehabilitation should be included as part of enhanced recovery after surgery for
      patients undergoing PD, although further large-scale studies are necessary to
      confirm our results.

PMID- 30219926
TI  - Error rates for unvalidated medical age assessment procedures.
AB  - During 2014-2015, Sweden received asylum applications from more than 240,000
      people, of which more than 40,000 were termed unaccompanied minors. In a large
      number of cases, claims by asylum seekers of being below 18 years were not
      trusted by Swedish authorities. To handle the situation, the Swedish national
      board of forensic medicine (Rattsmedicinalverket, RMV) was assigned by the
      government to create a centralized system for medical age assessments. RMV
      introduced a procedure including two biological age indicators; x-ray of the
      third molars and magnetic resonance imaging of the distal femoral epiphysis. In
      2017, a total of 9617 males and 337 females were subjected to this procedure. No
      validation study for the procedure was however published, and the observed number
      of cases with different maturity combinations in teeth and femur were unexpected
      given the claims originally made by RMV. We present a general stochastic model
      enabling us to study which combinations of age indicator model parameters and age
      population profiles are consistent with the observed 2017 data for males. We find
      that, contrary to some RMV claims, maturity of the femur, as observed by RMV,
      appears on average well before maturity of teeth. According to our estimates,
      approximately 15% of the tested males were children. These children had an
      approximate 33% risk of being classified as adults. The corresponding risk for an
      adult to be misclassified as a child was approximately 7%. We determine
      uncertainties and ranges of estimates under reasonable perturbations of the
      prior.

PMID- 30219928
TI  - A validation study of the Stoyanova et al. method (2017) for age-at-death
      estimation quantifying the 3D pubic symphyseal surface of adult males of European
      populations.
AB  - The age-at-death estimation thresholds have recently been shifted towards a more
      objective assessment of the aging process. Such a non-subjective approach offers
      quantitative methods of age estimation; for instance, the method relating to the
      surfaces of pubic symphyses of males published by Stoyanova et al. (J Forensic
      Sci 62:1434-1444, 2017). A validation study was conducted to test the method
      performance in European samples. The sample consisted of 96 meshes of pubic
      symphyses of male individuals (known sex and age) that came from four different
      samples (two Portuguese collections, one Swiss, and one Crete). Stoyanova's
      method based on five regression models (three univariate and two multivariate
      models) performed worse in our sample, but only when the whole sample (without
      age limitation) was included. A sample limited to individuals under 40 years of
      age achieved better results in our study. The best results were reached through
      the thin plate spline algorithm (TPS/BE) with a root mean square error of 5.93
      years and inaccuracy of 4.47 years. Generally, the multivariate regression models
      did not contribute to better age estimation. In our sample in all age categories,
      age was systematically underestimated. The quantitative method tested in this
      study works best for individuals under 40 years of age and provides a suitable
      basis for further research.

PMID- 30219927
TI  - Post-mortem distribution of the synthetic cannabinoid MDMB-CHMICA and its
      metabolites in a case of combined drug intoxication.
AB  - This case report centres on the post-mortem distribution of the synthetic
      cannabinoid MDMB-CHMICA and its metabolites in the case of a 27-year-old man
      found dead after falling from the 24th floor of a high-rise building.
      Toxicological analysis of post-mortem samples confirmed, besides consumption of
      the synthetic cannabinoids MDMB-CHMICA (1.7 ng/mL femoral blood) and EG-018, the
      abuse of THC (9.3 ng/mL femoral blood), amphetamine (1050 ng/mL femoral blood),
      MDMA (275 ng/mL femoral blood), and cocaine. Regarding EG-018 and cocaine, only
      traces were detected in heart blood as well as in the brain (EG-018) and urine
      (cocaine), respectively, which is why no quantification was conducted in the
      femoral blood sample. It was concluded from femoral blood analysis that, at the
      time of death, the man was under the influence of the synthetic cannabinoid MDMB
      CHMICA, THC, amphetamine and MDMA. Comprehensive screenings of all post-mortem
      specimens were conducted to elucidate the post-mortem distribution of MDMB-CHMICA
      and its metabolites. The MDMB-CHMICA concentrations ranged between 0.01 ng/mL
      (urine) and 5.5 ng/g (brain). Comparably low concentrations were detected in
      cardiac and femoral blood (2.1 ng/mL and 1.7 ng/mL, respectively) as well as in
      the psoas major muscle (1.2 ng/g). Higher concentrations were found in the lung
      (2.6 ng/g), liver (2.6 ng/g), and kidney (3.8 ng/g). Gastric content yielded a
      MDMB-CHMICA concentration of 2.4 ng/g (1.1 MUg absolute). Screening for MDMB
      CHMICA metabolites resulted in the detection of mainly monohydroxylated
      metabolites in the blood, kidney, and liver specimens. Results indicated that
      monohydroxylated metabolites of MDMB-CHMICA are appropriate target analytes for
      detecting MDMB-CHMICA intake.

PMID- 30219929
TI  - Prevalence of risk factors for chronic kidney disease in South African youth with
      perinatally acquired HIV.
AB  - BACKGROUND: Little is known about renal pathology among perinatally HIV-infected
      children and adolescents in Africa. We assessed the prevalence of risk factors
      for chronic kidney disease in South African children and adolescents with
      perinatally acquired HIV-1 (HIV+) on antiretroviral therapy (ART) and HIV
      negative children and adolescents. METHODS: HIV+ youth aged 9-14 years, on ART
      for > 6 months and age-matched HIV-negative children and adolescents were
      eligible for assessment of proteinuria and microalbuminuria using urine dipstick
      and Vantage analyser method. Blood pressure, estimated glomerular filtration
      rate, HIV-related variables and metabolic co-morbidities were assessed at
      enrolment. RESULTS: Among 620 children and adolescents, 511 were HIV+. The median
      age was 12.0 years and 50% were female. In HIV+ children and adolescents, 425
      (83.2%) had a CD4 count > 500 cells/mm3 and 391 (76.7%) had an undetectable viral
      load. The median duration of ART was 7.6 years (IQR 4.6-9.3) with 7 adolescents
      receiving Tenofovir. The prevalence of any proteinuria, microalbuminuria and
      hypertension was 6.6%, 8.5% and 13.9%, respectively, with no difference between
      HIV+ and negative children and adolescents. All participants had a normal
      glomerular filtration rate. There was no association between metabolic co
      morbidities and microalbuminuria. CONCLUSIONS: Proteinuria and microalbuminuria
      appear to be uncommon in this population. Follow up of those with
      microalbuminuria may inform long-term outcomes and management of this growing
      population of HIV+ youth.

PMID- 30219930
TI  - A first-principles study of pristine and Al-doped activated carbon interacting
      with 5-Fluorouracil anticancer drug.
AB  - The adsorption of the 5-Fluorouracil (5-FU) molecule on the pristine and Al-doped
      activated carbon (AC) was investigated by using the Vienna Ab-initio Simulation
      Package. It is found that the 5-FU molecule is only weakly adsorbed on the
      pristine AC with high adsorption energy and large surface distance. The
      adsorption of the 5-FU molecule on pristine AC is highly disfavored. In contrast,
      the molecule shows strong interactions with the Al-doped AC confirmed by the
      lesser adsorption energy, the charge transfers on the Al-modified zone and the
      significant changes in the DOS at the Fermi level. The results of our study
      suggest that the Al dopant increases the adsorption capacity of AC enhancing its
      interactions with polar atoms of the adsorbate, hence improving its adsorption
      properties.

PMID- 30219931
TI  - Carbon dioxide embolism during transanal total mesorectal excision (taTME).

PMID- 30219932
TI  - Comment on "A systematic review of minimally invasive surgery for retrorectal
      tumors".

PMID- 30219925
TI  - The peroxisome: an update on mysteries 2.0.
AB  - Peroxisomes are key metabolic organelles, which contribute to cellular lipid
      metabolism, e.g. the beta-oxidation of fatty acids and the synthesis of myelin
      sheath lipids, as well as cellular redox balance. Peroxisomal dysfunction has
      been linked to severe metabolic disorders in man, but peroxisomes are now also
      recognized as protective organelles with a wider significance in human health and
      potential impact on a large number of globally important human diseases such as
      neurodegeneration, obesity, cancer, and age-related disorders. Therefore, the
      interest in peroxisomes and their physiological functions has significantly
      increased in recent years. In this review, we intend to highlight recent
      discoveries, advancements and trends in peroxisome research, and present an
      update as well as a continuation of two former review articles addressing the
      unsolved mysteries of this astonishing organelle. We summarize novel findings on
      the biological functions of peroxisomes, their biogenesis, formation, membrane
      dynamics and division, as well as on peroxisome-organelle contacts and
      cooperation. Furthermore, novel peroxisomal proteins and machineries at the
      peroxisomal membrane are discussed. Finally, we address recent findings on the
      role of peroxisomes in the brain, in neurological disorders, and in the
      development of cancer.

PMID- 30219933
TI  - The Ostom-iTM Alert Sensor: a new device to measure stoma output.

PMID- 30219934
TI  - Suprapubic single-port approach for complicated diverticulitis.
AB  - BACKGROUND: Laparoscopic sigmoidectomy is the gold standard for elective surgical
      treatment of diverticulitis. A periumbilical single-port technique reduces the
      size of the access wound, usually to 3-4 cm. However, in the presence of large
      phlegmon or fistulae, the risk of conversion is higher and the extraction site
      might be enlarged. A suprapubic Pfannenstiel incision reduces the risk of
      incisional hernia compared to umbilical access and might provide the possibility
      to perform sigmoidectomy with a hybrid technique. The aim of the present study
      was to investigate the feasibility of laparoscopic sigmoidectomy through a single
      suprapubic transverse access for large diverticular phlegmon. METHODS:
      Consecutive patients with a diverticular inflammatory mass >= 5 cm, with or
      without sigmoid-vesical fistula, were considered candidates for laparoscopic
      sigmoidectomy through a 5-cm single-port suprapubic (SPSP) access, extended (if
      required) to match the size of the inflammatory mass. RESULTS: Twenty patients
      underwent SPSP sigmoidectomy at our institution in April 2014-April 2017. All
      procedures were completed by SPSP access, with no intraoperative complications or
      need for additional trocar placement. Eight patients had a sigmoid-vesical
      fistula (bladder sutured in three patients). The splenic flexure was mobilized in
      nine patients. Median operative time was 178 min and median hospital stay was 5.5
      days (iqr 4-6). Postoperative complications occurred in four patients and
      included one subcutaneous hematoma, one urinary tract infection, and two
      superficial wound infections. After a median follow-up time of 25 months
      (interquartile range 15-38), all patients experienced complete resolution of
      symptoms, with no incisional hernias reported. CONCLUSIONS: SPSP sigmoidectomy
      for diverticulitis is feasible and effective, minimizing the size of the access
      wound and avoiding increased risk of hernia. This approach might be especially
      valuable for the management of large diverticular phlegmon and sigmoid-vesical
      fistula.

PMID- 30219935
TI  - Automated ASPECT rating: comparison between the Frontier ASPECT Score software
      and the Brainomix software.
AB  - PURPOSE: Computer-aided diagnosis (CAD) appears promising in early ischemic
      change detection computed tomography (CT). This study aimed to compare the
      performance of two new CAD systems (Frontier ASPECTS Prototype and Brainomix)
      with two experienced readers in selected patients with suspected acute ischemic
      stroke. METHODS: Retrospectively, non-contrast brain CTs of 150 patients
      suspected for acute middle cerebral artery ischemia were analyzed with respect to
      ASPECTS first separately, than in consensus by two senior radiologists, and by
      use of Frontier and Brainomix. Besides the fully automatic Frontier and Brainomix
      readings (Frontier_1, Brainomix_1), readings adjusted for the affected brain side
      (known by CT angiography or clinical presentation, Frontier_2, Brainomix_2) were
      assessed. Statistical analysis was performed by intraclass correlation and Bland
      Altman statistics. RESULTS: The score-based ASPECTS readings of Brainomix_1,
      Brainomix_2, both radiologists, and the expert consensus reading correlated
      highly (r = 0.714 to 0.841; always p < 0.001), whereas Frontier_1 and Frontier_2
      correlated only lowly or moderately with both radiologists, the expert consensus
      reading, and Brainomix (r = 0.471 to 0.680; always p < 0.001). Bland-Altman
      analysis revealed lower mean ASPECT difference and standard deviation of
      difference for Brainomix_2 (mean difference = -0.2; SD = 1.15) compared to
      Frontier_2 (mean difference = 1.2; SD = 1.76). Correlation of region-based
      ASPECTS reading with the expert consensus reading was moderate for Brainomix_2 (r
      = 0.534), but only low for Frontier_2 (r = 0283; always p < 0.001). CONCLUSION:
      We found high agreement in ASPECTS rating between both radiologists, expert
      consensus reading, and Brainomix, but only low to moderate agreement to Frontier.

PMID- 30219936
TI  - Value of dual-energy CT angiography in patients with treated intracranial
      aneurysms.
AB  - PURPOSE: To evaluate the ability of dual-energy CT angiography (DECTA) in metal
      artifact reduction in patients with treated intracranial aneurysms by comparing
      DECTA-based virtual monoenergetic extrapolations (VMEs) and mixed images (MI).
      METHODS: Thirty-five patients underwent prospectively a dual-source DECTA
      (Somatom Force, Siemens Medical Solutions, Forchheim, Germany) after aneurysm
      repair. A total number of 40 aneurysms (23 treated by coil embolization and 17
      treated by surgical clipping) were analyzed. Mixed images (equivalent to a
      conventional single-energy CT angiography) were compared to VMEs at 75, 95, and
      115 keV. Artifact severity was assessed quantitatively by measuring the mean
      attenuation value and standard deviation within regions of interest placed in the
      most hypodense coil or clip artifact area. Artifact severity score and contrast
      vessel score were also assessed qualitatively by two independent blinded readers.
      RESULTS: In those aneurysms treated by surgical clipping, quantitative and
      qualitative analyses showed significant reduction of artifacts on VMEs compared
      to MI with the best compromise being obtained at 95 keV in order to keep an
      optimal vessel contrast in the adjacent vessel. In those aneurysms treated by
      coil embolization, there was no significant reduction of artifacts both on
      quantitative and qualitative analyses. CONCLUSION: Dual-source DECTA was helpful
      in order to reduce clip artifacts on VMEs with the optimal adjacent vessel
      visualization obtained at 95 keV, whereas this technique was not helpful in
      aneurysms treated by coiling.

PMID- 30219937
TI  - Quality of life of persons living with HIV and congruence with surrogate decision
      makers.
AB  - PURPOSE: Physicians and caregivers rate patient quality of life (QOL) lower than
      patients rate their own QOL. This study investigated discrepancies between self
      assessments of patient QOL by adults with HIV and their surrogate decision
      makers. METHODS: We collected baseline data from 223 adult dyads in the FAmily
      CEntered (FACE) Advance Care Planning (ACP) clinical trial, consisting of HIV
      positive patients and their chosen surrogates. Participants independently
      completed the Medical Outcome Study-HIV Survey (MOS-HIV) and the Palliative care
      Outcome Scale (POS). We used Wilcoxon Signed-Rank Test to assess differences in
      overall patient-surrogate means. We used Prevalence Adjusted Bias Adjusted Kappa
      (PABAK) statistics to assess dyadic agreement, with surrogate HIV status and
      cohabitation status as grouping variables. RESULTS: Patients were 56.1% male,
      86.1% Black/African-American, aged 22-77 (mean = 50.83, SD = +/- 12.33).
      Surrogates were 43.8% male, 84.1% Black/African-American, aged 18-82 (mean =
      49.73, SD = +/- 14.22). 46.2% of surrogates lived with the patient. 64.6% of
      surrogates reported negative HIV status. Surrogates were more likely to state
      patients were ill, p = 0.032. Among patient-surrogate dyads, most QOL assessments
      showed poor (0.00-0.39) or fair (0.40-0.59) agreement and agreement tended to be
      even poorer among patient-surrogate dyads where the surrogate had a shared HIV
      diagnosis. CONCLUSIONS: QOL discrepancies are said to arise from healthy
      surrogates overestimating the effects of chronic illness. In this novel
      assessment, many surrogates had a shared HIV diagnosis, without increased
      agreement. These findings highlight the challenge of accurately assessing patient
      QOL by surrogates, even when there is a shared HIV diagnosis. Improved
      communication is needed between patients and surrogates about the patients'
      representation of illness. National Clinical Trial Number: NCT01775436.

PMID- 30219938
TI  - Percutaneous nephrostomy vs ureteral stent for hydronephrosis secondary to
      ureteric calculi: impact on spontaneous stone passage and health-related quality
      of life-a prospective study.
AB  - Ureteral calculi can be associated with urinary drainage blockage, requiring
      urinary diversion with percutaneous nephrostomy (PCN) or retrograde ureteral
      stent (RUS). Currently no evidence exists to support the superiority of one
      method over the other. This study proposes to compare both approaches regarding
      the probability of spontaneous stone passage (SSP) and its effect on patient's
      quality of life (QoL). A prospective trial was carried out from July to October
      of 2017. 50 patients were selected with hydronephrosis secondary to ureteral
      stones requiring urgent urinary diversion and divided into two groups according
      to diversion technique: percutaneous nephrostomy (PCN) or retrograde ureteral
      stent (RUS). The rate of SSP and QoL were evaluated. A PCN group (18 patients)
      and a RUS group (32 patients) were set. Stone size was higher in PCN (median 92
      mm2) than RUS (median 47 mm2) (p = .012). The rate of SSP was 25% in RUS group
      and 38.9% in PCN. On the univariable analysis no statistical effect was found;
      however, when adjusted for stone size, location, previous ureteral manipulation
      and expulsive therapy, PCN showed a significant higher chance of SSP than RUS (OR
      = 6667). Besides, it was found that 30.2% (n = 13) of stones had an upward
      displacement associated with retrograde endoscopy. A significant decrease between
      pre- and post-intervention QoL was found with RUS (p < .001), but not found with
      PCN (p = .206). Patients in RUS group experienced more urinary symptoms, mostly
      haematuria (68.7% vs 16.7% in PCN group < .001) and dysuria (78.3% vs 16.7% in
      PCN group, p < .001). PCN was associated with a higher rate of spontaneous stone
      passage when adjusted for stone size and location. Moreover, PCN was better
      tolerated and associated with fewer urinary symptoms when compared with RUS.

PMID- 30219939
TI  - Sex and age interact to determine clinicopathologic differences in Alzheimer's
      disease.
AB  - Women reportedly make up two-thirds of Alzheimer's disease (AD) dementia
      sufferers. Many estimates regarding AD, however, are based on clinical series
      lacking autopsy confirmation. The Florida Autopsied Multi-Ethnic (FLAME) cohort
      was queried for AD cases with a total of 1625 identified ranging in age from 53
      to 102 years at death. Standard neuropathologic procedures were employed and
      clinical information was retrospectively collected. Clinicopathologic and genetic
      data (MAPT and APOE) were stratified by sex. Within the neuropathologically
      diagnosed AD cohort, the overall number of women and men did not differ. Men were
      younger at onset of cognitive symptoms, had a shorter disease duration, and more
      often had atypical (non-amnestic) clinical presentations. The frequency of
      autopsy-confirmed AD among women and men stratified by age at death revealed an
      inverse U-shaped curve in men and a U-shaped curve in women, with both curves
      having inflections at approximately 70 years of age. Regional counts of
      neurofibrillary tangles differed in women and men, especially when examined by
      age intervals. Women had overall greater severity of neurofibrillary tangle
      counts compared to men, especially in the hippocampus. Men were more often
      classified as hippocampal sparing AD, whereas limbic predominant AD was more
      common in women. Men and women did not differ in frequency of MAPT haplotype or
      APOE genotype. Atypical clinical presentations, younger age at onset and shorter
      disease duration were more frequent in men, suggesting that the lower reported
      frequency of AD in men may be due to more frequent atypical clinical
      presentations not recognized as AD. Our data suggest that neuropathologically
      diagnosed AD cases have the same frequency of women and men, but their clinical
      presentations and ages at onset tend to differ.

PMID- 30219940
TI  - Nodding syndrome in Uganda is a tauopathy.
AB  - Nodding syndrome is an epidemic neurologic disorder of unknown cause that affects
      children in the subsistence-farming communities of East Africa. We report the
      neuropathologic findings in five fatal cases (13-18 years of age at death) of
      nodding syndrome from the Acholi people in northern Uganda. Neuropathologic
      examination revealed tau-immunoreactive neuronal neurofibrillary tangles, pre
      tangles, neuropil threads, and dot-like lesions involving the cerebral cortex,
      subcortical nuclei and brainstem. There was preferential involvement of the
      frontal and temporal lobes in a patchy distribution, mostly involving the crests
      of gyri and the superficial cortical lamina. The mesencephalopontine tegmental
      nuclei, substantia nigra, and locus coeruleus revealed globose neurofibrillary
      tangles and threads. We conclude that nodding syndrome is a tauopathy and may
      represent a newly recognized neurodegenerative disease.

PMID- 30219941
TI  - Differences in possible TCA cycle replenishing pathways in purple non-sulfur
      bacteria possessing glyoxylate pathway.
AB  - Pathways replenishing tricarboxylic acid cycle were divided into four major
      groups based on metabolite serving as source for oxaloacetic acid or other
      tricarboxylic acid cycle component synthesis. Using this metabolic map, the
      analysis of genetic potential for functioning of tricarboxylic acid cycle
      replenishment pathways was carried out for seven strains of purple non-sulfur
      bacterium Rhodopseudomonas palustris. The results varied from strain to strain.
      Published microarray data for phototrophic acetate cultures of Rps. palustris
      CGA009 were analyzed to validate activity of the putative pathways. All the
      results were compared with the results for another purple non-sulfur bacterium,
      Rhodobacter capsulatus SB1003 and species-specific differences were clarified.

PMID- 30219942
TI  - In memory of Thomas Turpin Bannister (1930-2018).
AB  - Tom Bannister (1930-2018) was an extraordinary person and a remarkably productive
      scientist. He began his career studying the basics of photochemistry, biophysics,
      and biology of photosynthetic pigments and later moved on to primary production
      of algae. His publications on modeling of primary production rates in aquatic
      systems are among the most widely cited in the field of phytoplankton ecology.
      His scientific enthusiasm was contagious, and his knowledge of photosynthesis and
      phytoplankton ecology enabled him to wisely mentor an impressive group of
      graduate students. He encouraged his students to strike out on their own but was
      always supportive and caring. Tom had a great love of life and nature, and he had
      a wonderful sense of humor. His students and those with whom he interacted
      remember him with great fondness. We have included here remembrances from some of
      us as well as from Rich Dempsey; Michael (Mike) Johnson; Stephen Lien; Janet
      Pelley; Bruce Selman; and Rudy Slovacek.

PMID- 30219943
TI  - Cognitive functioning and functional brain networks in postoperative WHO grade I
      meningioma patients.
AB  - INTRODUCTION: Meningioma patients often have subtle cognitive deficits that might
      be attributed to the tumor itself, to surgical treatment, or to the occurrence of
      seizures and their treatment. Magnetoencephalography (MEG) analysis of resting
      state functional networks (RSNs) could help to understand the neurophysiological
      basis of cognitive impairment in these patients. We explored the correlation
      between RSN functional connectivity and topology of functional networks on the
      one hand, and cognition on the other hand in WHO grade I meningioma patients.
      METHODS: Twenty adult WHO grade I meningioma patients who had undergone tumor
      resection, as well as 20 healthy matched controls, were included.
      Neuropsychological assessment was done through a standardized test battery. MEG
      data were recorded, and projected to the anatomical space of the Automated
      Anatomical Labeling atlas. Functional connectivity (PLI), within the default mode
      network (DMN) and the bilateral frontoparietal networks were correlated to
      cognitive performance. Minimum spanning tree (MST) characteristics were
      correlated with cognitive functioning. RESULTS: Compared to healthy controls,
      meningioma patients had lower working memory capacity (p = 0.037). Within the
      patient group, lower working memory performance was associated with lower DMN
      connectivity and a lower maximum MST degree in the theta band (resp. p = 0.044
      and p = 0.003). CONCLUSIONS: This study shows that cognitive functioning is
      correlated with functional connectivity in the default mode network and hub
      pathology in WHO grade I meningioma patients. Future longitudinal studies are
      needed to corroborate these findings and to further investigate the
      pathophysiology of cognitive deficits and possible changes in functional brain
      networks in meningioma patients.

PMID- 30219944
TI  - Modifications of the axon initial segment during the hibernation of the Syrian
      hamster.
AB  - Mammalian hibernation is a natural process in which the brain undergoes profound
      adaptive changes that appear to protect the brain from extreme hypoxia and
      hypothermia. In addition to a virtual cessation of neural and metabolic activity,
      these changes include a decrease in adult neurogenesis; the retraction of
      neuronal dendritic trees; changes in dendritic spines and synaptic connections;
      fragmentation of the Golgi apparatus; and the phosphorylation of the microtubule
      associated protein tau. Furthermore, alterations of microglial cells also occur
      in torpor. Importantly, all of these changes are rapidly and fully reversed when
      the animals arouse from torpor state, with no apparent brain damage occurring.
      Thus, hibernating animals are excellent natural models to study different aspects
      of brain plasticity. The axon initial segment (AIS) is critical for the
      initiation of action potentials in neurons and is an efficient site for the
      regulation of neural activity. This specialized structure-characterized by the
      expression of different types of ion channels and adhesion, scaffolding and
      cytoskeleton proteins-is subjected to morpho-functional plastic changes upon
      variations in neural activity or in pathological conditions. Here, we used
      immunocytochemistry and 3D confocal microscopy reconstruction techniques to
      measure the possible morphological differences in the AIS of neocortical (layers
      II-III and V) and hippocampal (CA1) neurons during the hibernation of the Syrian
      hamster. Our results indicate that the general integrity of the AIS is resistant
      to the ischemia/hypoxia conditions that are characteristic of the torpor phase of
      hibernation. In addition, the length of the AIS significantly increased in all
      the regions studied-by about 16-20% in torpor animals compared to controls,
      suggesting the existence of compensatory mechanisms in response to a decrease in
      neuronal activity during the torpor phase of hibernation. Furthermore, in double
      labeling experiment, we found that the AIS in layer V of torpid animals was
      longer in neurons expressing phospho-tau than in those not labeled for phospho
      tau. This suggests that AIS plastic changes were more marked in phospho-tau
      accumulating neurons. Overall, the results further emphasize that mammalian
      hibernation is a good physiological model to study AIS plasticity mechanisms in
      non-pathological conditions.

PMID- 30219945
TI  - Late toxicity of image-guided hypofractionated radiotherapy for prostate: non
      randomized comparison with conventional fractionation.
AB  - PURPOSE: To evaluate the incidence and predictors for late toxicity and tumor
      outcome after hypofractionated radiotherapy using three different image-guided
      radiotherapy (IGRT) systems (hypo-IGRT) compared with conventional fractionation
      without image guidance (non-IGRT). METHODS AND MATERIALS: We compared the late
      rectal and urinary toxicity and outcome in 179 prostate cancer patients treated
      with hypo-IGRT (70.2 Gy/26 fractions) and 174 non-IGRT patients (80 Gy/40
      fractions). Multivariate analysis was performed to define predictors for late
      toxicity. 5- and 8-year recurrence-free survival (RFS) and overall survival (OS)
      were analyzed. RESULTS: Mean follow-up was 81 months for hypo-IGRT and 90 months
      for non-IGRT group. Mainly mild late toxicity was observed: Hypo-IGRT group
      experienced 65 rectal (30.9% G1/G2; 6.3% G3/G4) and 105 urinary events (56%
      G1/G2; 4% G3/G4). 5- and 8-year RFS rates were 87.5% and 86.8% (hypo-IGRT) versus
      80.4% and 66.8% (non-IGRT). 5- and 8-year OS rates were 91.3% and 82.7% in hypo
      IGRT and 92.2% and 84% in non-IGRT group. Multivariate analysis showed that hypo
      IGRT is a predictor for late genitourinary toxicity, whereas hypo-IGRT, acute
      urinary toxicity and androgen deprivation therapy are predictors for late rectal
      toxicity. Advanced T stage and higher Gleason score (GS) were correlated with
      worse RFS. CONCLUSIONS: A small increase in mild late toxicity, but not
      statistically significant increase in severe late toxicity in the hypo-IGRT group
      when compared with conventional non-IGRT group was observed. Our study confirmed
      that IGRT allows for safe moderate hypofractionation, offering a shorter overall
      treatment time, a good impact in terms of RFS and providing potentially more
      economic health care.

PMID- 30219946
TI  - Stimulation history affects vasomotor responses in rat mesenteric arterioles.
AB  - Resistance vessels regulate blood flow by continuously adjusting activity of the
      wall smooth muscle cells. These cells integrate a variety of stimuli from blood,
      endothelium, autonomic nerves, and surrounding tissues. Each stimulus elicits an
      intracellular signaling cascade that eventually influences activation of the
      contractile machinery. The characteristic time scale of each cascade and the
      sharing of specific reactions between cascades provide for complex behavior when
      a vessel receives multiple stimuli. Here, we apply sequential stimulation with
      invariant concentrations of vasoconstrictor (norepinephrine/methoxamine) and
      vasodilator (SNAP/carbacol) to rat mesenteric vessels in the wire myograph to
      show that (1) time elapsed between addition of two vasoactive drugs and (2) the
      sequence of addition may significantly affect final force development.
      Furthermore, force oscillations (vasomotion) often appear upon norepinephrine
      administration. Using computational modeling in combination with nitric oxide
      (NO) inhibition/NO addition experiments, we show that (3) amplitude and number of
      oscillating vessels increase over time, (4) the ability of NO to induce
      vasomotion depends on whether it is applied before or after norepinephrine, and
      (5) emergence of vasomotion depends on the prior dynamical state of the system;
      in simulations, this phenomenon appears as "hysteresis." These findings
      underscore the time-dependent nature of vascular tone generation which must be
      considered when evaluating the vasomotor effects of multiple, simultaneous
      stimuli in vitro or in vivo.

PMID- 30219947
TI  - Within- and between-year variations of reproductive strategy and cost in a
      population of Siberian chipmunks.
AB  - Reproduction costs depend on the general life-history strategies employed by
      organisms for resource acquisition, the decision rules on resource allocation,
      and the resource availability. Although the predictability of resource
      availability is expected to influence the breeding strategy, the relationship
      between predictability and strategy has rarely been investigated at the
      population level. One reason is that, while the resource availability is commonly
      variable in space and time, their predictability is generally assumed constant.
      Here, we addressed the temporal variation of the breeding strategy and its
      associated survival cost in a hibernating population of Tamias sibiricus, in
      which food resources vary in their availability between years and in their
      predictability within years. Based on 11 years of mark-recapture data, we used
      multi-event modelling to investigate seasonal variations in reproduction costs of
      female chipmunks that breed twice a year (spring and summer). In summer, during
      which a large variety and quantity of resources is available (income breeding
      strategy), the proportion of breeding females was consistent across years and
      reproduction yielded no mortality cost. In contrast, in spring, the proportion of
      breeding females was positively correlated with the amount of resources available
      for hibernation (partial capital breeding strategy). Spring reproduction yielded
      no immediate cost, but induced a delayed mortality cost over the next winter if
      future unknown conditions were unfavorable. Our findings highlight complex
      temporal reproductive patterns in a short-lived species: not only does the
      modality of resource acquisition vary among seasons, but also the decision rule
      to breed and its associated cost.

PMID- 30219949
TI  - Avifauna conservation and disturbance ecology in a coastal freshwater lagoon.
AB  - This work was developed in Barrinha de Mira Coastal Lagoon, Portugal. The lagoon
      belongs to the Natura 2000 network. Its main objectives were to monitor aquatic
      bird species before, during, and after a desorption intervention on this lagoon.
      Monitoring of waterfowl was carried out to evaluate the monthly variation of
      birds in Barrinha, in order to obtain useful information for region's management
      and planning, as well as for species preservation. In experimental design, it was
      decided to perform four counts per month in each pond (weekly), to evaluate the
      effect of increased monitoring effort in relation to previous years. The results
      revealed that the study area has a significant importance as a wintering zone for
      water birds. Some species have stable resident populations which, seasonally, see
      their numbers vary with migratory birds arrival and departure. Another purpose
      was to verify the influence of desorption intervention on the usual number of
      individuals by species. The results show that during and after intervention,
      there was a reduction of birds in the order of 89%, being more visible in the
      populations of Anas platyrhynchos and Fulica atra.

PMID- 30219950
TI  - Replacement Effects and Budget Impacts of Insurance Coverage for Sodium-Glucose
      Co-Transporter-2 Inhibitors on Oral Antidiabetic Drug Utilization.
AB  - BACKGROUND AND OBJECTIVES: A new oral antidiabetic drug class, sodium-glucose co
      transporter-2 inhibitors (SGLT-2 inhibitors), has been covered by national health
      insurance in Taiwan since May 2016. This study estimated the impacts of insurance
      coverage for SGLT-2 inhibitors on the replacement effects of antidiabetic drug
      use and the overall budget for antidiabetic drugs in Taiwan. METHODS:
      Antidiabetic drugs were divided into nine categories based on the American
      Diabetes Association guidelines. We retrieved claims data from 2015 to 2017 for
      all patients diagnosed with diabetes mellitus from the National Health Insurance
      Research Database. An interrupted time series design and segmented regression
      were used to estimate the budget impact of insurance coverage for SGLT-2
      inhibitors. Three scenarios were designed for the prescribing pattern for SGLT-2
      inhibitors: (1) monotherapy, (2) metformin-based (m-based) drug prescriptions,
      and (3) metformin and sulfonylurea-based (m-s-based) drug prescriptions. RESULTS:
      From May 2016 to April 2017, the prescription rate for m-based SGLT-2 inhibitors
      increased from 0.43 to 3.50%, and the expenditure rate increased from 0.82 to
      6.58%. We found that the prescription rates of m-based and m-s-based dipeptidyl
      peptidase-4 inhibitors (DPP-4 inhibitors) decreased by 6.23 and 11.51% following
      the initiation of insurance coverage for SGLT-2 inhibitors, respectively.
      Furthermore, there was a 5.95% increase in the overall budget impact of
      antidiabetic drugs 1 year following the initiation of insurance coverage for SGLT
      2 inhibitors. CONCLUSIONS: Both the prescription rates and expenditure rates for
      SGLT-2 inhibitors have increased since they have been covered by national health
      insurance in Taiwan, which significantly reduced usage of DPP-4 inhibitors but
      caused the positive growth of overall antidiabetic drug expenditures.

PMID- 30219948
TI  - Thermus sediminis sp. nov., a thiosulfate-oxidizing and arsenate-reducing
      organism isolated from Little Hot Creek in the Long Valley Caldera, California.
AB  - Thermus species are widespread in natural and artificial thermal environments.
      Two new yellow-pigmented strains, L198T and L423, isolated from Little Hot Creek,
      a geothermal spring in eastern California, were identified as novel organisms
      belonging to the genus Thermus. Cells are Gram-negative, rod-shaped, and non
      motile. Growth was observed at temperatures from 45 to 75  degrees C and at
      salinities of 0-2.0% added NaCl. Both strains grow heterotrophically or
      chemolithotrophically by oxidation of thiosulfate to sulfate. L198T and L423 grow
      by aerobic respiration or anaerobic respiration with arsenate as the terminal
      electron acceptor. Values for 16S rRNA gene identity (<= 97.01%), digital DNA-DNA
      hybridization (<= 32.7%), OrthoANI (<= 87.5%), and genome-to-genome distance
      (0.13) values to all Thermus genomes were less than established criteria for
      microbial species. The predominant respiratory quinone was menaquinone-8 and the
      major cellular fatty acids were iso-C15:0, iso-C17:0 and anteiso-C15:0. One
      unidentified phospholipid (PL1) and one unidentified glycolipid (GL1) dominated
      the polar lipid pattern. The new strains could be differentiated from related
      taxa by beta-galactosidase and beta-glucosidase activity and the presence of
      hydroxy fatty acids. Based on phylogenetic, genomic, phenotypic, and
      chemotaxonomic evidence, the novel species Thermus sediminis sp. nov. is
      proposed, with the type strain L198T (= CGMCC 1.13590T = KCTC XXX).

PMID- 30219951
TI  - Multicenter, Open-Label Study of Long-Term Topiroxostat (FYX-051) Administration
      in Japanese Hyperuricemic Patients with or Without Gout.
AB  - BACKGROUND AND OBJECTIVES: Topiroxostat-a novel selective xanthine oxidoreductase
      inhibitor-has been reported to reduce serum urate levels. The purpose of this
      study was to assess the efficacy and safety of long-term topiroxostat
      administration in Japanese hyperuricemic patients with or without gout. METHODS:
      This multicenter, open-label study evaluated the efficacy and safety of long-term
      twice-daily oral topiroxostat administration in patients with or  without gout.
      The initial topiroxostat dosage was 40-80 mg/day, and the maintenance dosage was
      120 mg/day, which was increased to 240 mg/day at 40 mg increments if the serum
      urate level exceeded 6.0 mg/dL. RESULTS: Serum urate level, which was the primary
      endpoint, decreased stably over time and showed significant reduction on the
      final visit (38.44% +/- 13.34%) compared with that at the baseline. Both urinary
      albumin/creatinine ratio and mean blood pressure significantly improved. The
      overall incidence rate of adverse drug reactions to topiroxostat was 67.8%; on
      the final visit, the rate of adverse drug reactions was 66.7% with 120 mg/day,
      72.2% with 160 mg/day, 53.8% with >= 200 mg/day, and 100% with the other dosages.
      On the final visit, the incidence of gouty arthritis, for which a causal
      relationship with topiroxostat could not be ruled out, was 4.1% overall, 4.8%
      with 120 mg/day, 0% with 160 mg/day, and 7.7% with >= 200 mg/day. CONCLUSIONS: We
      verified the efficacy and safety of 58-week oral topiroxostat administration at
      stepwise increments to up to 240 mg/day. STUDY REGISTRATION: JAPIC CTI-101068.

PMID- 30219952
TI  - Nanomedicines for developing cancer nanotherapeutics: from benchtop to bedside
      and beyond.
AB  - Cancer is a devastating disease and remains a significant cause of mortality and
      morbidity in both developed and developing countries. Although there are large
      number of drugs that can be used for the treatment of cancer, the problem is
      selective and specific killing of cancerous cells without harming the normal
      cells. There are some biological barriers to potential drug delivery in cancer
      cells like hepatic, renal, abnormal vasculature, dense extracellular matrix, and
      high interstitial fluid pressure. The physicochemical characteristics of
      nanoparticles (NPs) such as size, shape, and surface charge may also have
      significant effects on tumor penetration. NPs coated with drug can be used to
      overcome these biological barriers to enhance targeted delivery. This literature
      survey encompasses the biological barriers to potential drug delivery in cancer
      cells, elaborate on designing strategies to enhance NPs penetration and
      distribution inside the tumor interstitium. Scientists are now doing great
      efforts to design next-generation of nanomedicines (NMs) that need to be better
      targeted with high specificity and efficacy to kill cancer cells. These
      challenges need to be overcome through collaborations among academia,
      pharmaceutical industries, and regulatory agencies to eradicate this global
      menace. Furthermore, this review article has critically discussed the recent
      developments, controversies, challenges, emerging concepts, and future
      perspectives in cancer NMs.

PMID- 30219955
TI  - Factors influencing early postoperative complications following surgery for
      symptomatic spinal metastasis: a single-center series and multivariate analysis.
AB  - Patients presenting with neurological deficits and/or pain due to spinal
      metastasis usually require immediate or subacute surgical treatment.
      Nevertheless, it is unclear whether or not side effects of primary cancer
      location might influence postoperative complication rate. We therefore analyzed
      our spinal database to identify factors influencing early postoperative
      complications after surgery for symptomatic spinal metastases. From 2013 to 2017,
      163 consecutive patients suffering from symptomatic spinal metastases were
      treated at our department. Early postoperative complications were defined as any
      postoperative event requiring additional medical or surgical treatment within 30
      days of spinal surgery. A multivariate regression analysis was performed to
      identify independent predictors for postoperative complications after surgery for
      spinal metastasis. Overall, 39 of 163 patients who underwent spinal surgery for
      spinal metastasis developed early postoperative complications throughout the
      treatment course (24%). Preoperative ASA score >= 3 (p = 0.003), preoperative C
      reactive protein level > 10 mg/l (p = 0.008), preoperative Karnofsky Performance
      Score < 60% (p = 0.03), radiation treatment within 2 months of surgery (p =
      0.01), presence of diabetes mellitus (p = 0.008), and preoperative complete
      neurological impairment (p = 0.04) were significant and independent predictors
      for early postoperative complications in patients with surgery for spinal
      metastasis. The ability to preoperatively predict postoperative complication risk
      is valuable to select critically ill patients at higher risk requiring special
      attention. Therefore, the present study identified several significant and
      independent risk factors for the development of early postoperative complication
      in patients who underwent surgery for spinal metastasis.

PMID- 30219954
TI  - Long-term survival of a patient with recurrent gallbladder carcinoma, treated
      with chemotherapy, immunotherapy, and surgery: a case report.
AB  - BACKGROUND: Gallbladder cancer (GBC) is one of the refractory diseases.
      Multidisciplinary approach including immunotherapy for such cancers has received
      much attention in recent years. CASE PRESENTATION: A 59-year-old man underwent an
      extended cholecystectomy for GBC (pathological stage II, T2 N0 M0, [per UICC 7th
      edition]) that was incidentally found during cholelithiasis surgery, and was then
      treated with adjuvant gemcitabine (GEM). Three months later, when a recurrence
      suspected lesion was detected in segment 5 (S5) of his liver, we started adoptive
      immunotherapies with cytokine-activated killer (CAK) cell infusions, combined
      with chemotherapy. After a year of adjuvant immunochemotherapy, the S5 lesion
      disappeared on imaging, but lesions suspected metastatic recurrence again
      appeared in S7 and S8 at 4 years and 6 months post-surgery, for which GEM and
      cisplatin (CDDP) were administered as second-line chemotherapy.
      Immunochemotherapy produced stable disease (per RECIST) for 9 months, when tumor
      growth was detected; open microwave coagulo-necrotic therapy (MCN) was performed
      for these lesions. Three years after MCN, a solitary liver metastasis was
      detected in S4. MCN was conducted again, and peritoneal dissemination was found
      intraoperatively. A month after the second MCN, the patient's carcinoembryonic
      antigen (CEA) level had increased. Therefore, GEM and tegafur-gimeracil-oteracil
      potassium (TS-1) were administered as third-line chemotherapy. We also switched
      the adoptive immunotherapy for tumor-associated antigen-pulsed dendritic cell
      activated killer (DAK) cell immunotherapy. After nine courses of GEM and TS-1
      administration, CEA had decreased to a normal level. At the time of reporting, 9
      years and 6 months have passed since the initial surgery, and 18 months have
      passed since the peritoneal metastasis was detected. GEM and CDDP are currently
      administered as fourth-line chemotherapy because of re-increased CEA. Although an
      undeniable metastasis was found in his para-aortic lymph node, this patient
      visits our clinic regularly for immunotherapy. CONCLUSION: We here report a rare
      case of long-term survival of recurrent GBC well controlled by multidisciplinary
      therapy. Immunotherapy may be a promising modality among multidisciplinary
      methods for advanced cancer.

PMID- 30219956
TI  - Impedimetric determination of Staphylococcal enterotoxin B using electrochemical
      switching with DNA triangular pyramid frustum nanostructure.
AB  - An electrochemical switching strategy is presented for the sensitive
      determination of Staphylococcus enterotoxin B (SEB). It is based on the use of
      DNA triangular pyramid frustum nanostructure (TPFDNA) consisting of (a) three
      thiolated probes, (b) one auxiliary probe, and (c) an aptamer against SEB. The
      TPFDNA was assembled on the gold electrode, with the SEB aptamer designed on top
      of the TPFDNA. The electron transfer to hexacyanoferrate acting as an
      electrochemical probe is strongly inhibited in the TPFDNA-modified electrode.
      This is assumed to be due to the formation of a 3D TPFDNA structure that limits
      access of hexacyanoferrate to the electrode. Therefore, the Faradaic impedance is
      large. However, in the presence of SEB, it will bind to the aptamer and
      dehybridize the hybrid formed between aptamer and its complementary sequence. As
      a result, the TPFDNA nanostructure changes to an equilateral triangle DNA
      nanostructure. This results in a more efficient electron transfer and a smaller
      Faradaic impedance. The method has a detection limit of 0.17 ng mL-1 of SEB (at
      an S/N of 3) and a dynamic range that covers the 0.2-1000 ng mL-1 concentration
      range. The applicability and reliability of the method was demonstrated by
      anayzing (spiked) milk samples, and the results were compared to those obtained
      with an ELISA kit. The relative standard deviations between the two methods range
      between -6.59 and 9.33%. Graphical abstract An electrochemical switching strategy
      is presented for the sensitive detection of Staphylococcus enterotoxin B based on
      3D DNA structure conversion of nanostructure from triangular pyramid frustum to
      equilateral triangle.

PMID- 30219957
TI  - Approach to record linkage of primary care data from Clinical Practice Research
      Datalink to other health-related patient data: overview and implications.
AB  - Record linkage is increasingly used to expand the information available for
      public health research. An understanding of record linkage methods and the
      relevant strengths and limitations is important for robust analysis and
      interpretation of linked data. Here, we describe the approach used by Clinical
      Practice Research Datalink (CPRD) to link primary care data to other patient
      level datasets, and the potential implications of this approach for CPRD data
      analysis. General practice electronic health record software providers separately
      submit de-identified data to CPRD and patient identifiers to NHS Digital,
      excluding patients who have opted-out from contributing data. Data custodians for
      external datasets also send patient identifiers to NHS Digital. NHS Digital uses
      identifiers to link the datasets using an 8-stage deterministic methodology. CPRD
      subsequently receives a de-identified linked cohort file and provides researchers
      with anonymised linked data and metadata detailing the linkage process. This
      methodology has been used to generate routine primary care linked datasets,
      including data from Hospital Episode Statistics, Office for National Statistics
      and National Cancer Registration and Analysis Service. 10.6 million (M) patients
      from 411 English general practices were included in record linkage in June 2018.
      9.1M (86%) patients were of research quality, of which 8.0M (88%) had a valid NHS
      number and were eligible for linkage in the CPRD standard linked dataset release.
      Linking CPRD data to other sources improves the range and validity of research
      studies. This manuscript, together with metadata generated on match strength and
      linkage eligibility, can be used to inform study design and explore potential
      linkage-related selection and misclassification biases.

PMID- 30219958
TI  - Perspective-Taking in Referential Communication: Does Stimulated Attention to
      Addressees' Perspective Influence Speakers' Reference Production?
AB  - In two experiments, we investigated whether speakers' referential communication
      benefits from an explicit focus on addressees' perspective. Dyads took part in a
      referential communication game and were allocated to one of three experimental
      settings. Each of these settings elicited a different perspective mind-set
      (baseline, self-focus, other-focus). In the two perspective settings, speakers
      were explicitly instructed to regard their addressees' (other-focus) or their own
      (self-focus) perspective before construing their referential message. Results
      evidenced speakers' egocentricity bias. Even though speakers were explicitly
      aware of addressees' informational need, speakers still referred to information
      not known to their addressee. Speakers' self-reported perspective-taking behavior
      correlated with their actual reference behavior. Those who reported to have
      regarded addressees' perspective were also less likely to have leaked information
      about their own knowledge and attentional state. Findings are discussed in light
      of speakers' egocentricity bias and the role of speaker-addressee collaboration
      in language production.

PMID- 30219959
TI  - The Influence of Presentation Format of Story on Narrative Production in Chinese
      Children Learning English-as-a-Second-Language: A Comparison Between Graphic
      Novel, Illustration Book and Text.
AB  - Past studies have shown that multimodal presentation of story can improve story
      retelling performance in the first language. The purpose of the present study was
      to investigate whether similar multimedia effects can be observed in second
      language learning and graphic novel reading. A total of 51 Chinese elementary
      school children, aged 7-8, who were learning English as a second language were
      recruited. They were randomly assigned to one of the three experimental
      conditions that differed in the format of story presentation: English text,
      English text with pictorial illustrations or graphic novel. After reading the
      same story, the children retold the story in English. The narratives produced
      were then rated by two independent raters. The results of group comparison showed
      that children from the three experimental groups had similar performance,
      indicating that multimedia presentation may not always facilitate narrative
      production in English as a second language. Within-subject comparison further
      showed that the children were relatively strong in language skills and capturing
      the main ideas of the story, while showing weakness in story structure awareness,
      elaboration, as well as local and global cohesion. Suggestions for the
      application of multimodal presentation of narrative texts are discussed.

PMID- 30219960
TI  - Transcriptome analysis of Panax zingiberensis identifies genes encoding oleanolic
      acid glucuronosyltransferase involved in the biosynthesis of oleanane-type
      ginsenosides.
AB  - MAIN CONCLUSION: Oleanolic acid glucuronosyltransferase (OAGT) genes synthesizing
      the direct precursor of oleanane-type ginsenosides were discovered. The four
      recombinant proteins of OAGT were able to transfer glucuronic acid at C-3 of
      oleanolic acid that yields oleanolic acid 3-O-beta-glucuronide. Ginsenosides are
      the primary active components in the genus Panax, and great efforts have been
      made to elucidate the mechanisms underlying dammarane-type ginsenoside
      biosynthesis. However, there is limited information on oleanane-type
      ginsenosides. Here, high-performance liquid chromatography analysis demonstrated
      that oleanane-type ginsenosides (particularly ginsenoside Ro and
      chikusetsusaponin IV and IVa) are the abundant ginsenosides in Panax
      zingiberensis, an extremely endangered Panax species in southwest China. These
      ginsenosides are derived from oleanolic acid 3-O-beta-glucuronide, which may be
      formed from oleanolic acid catalyzed by an unknown oleanolic acid
      glucuronosyltransferase (OAGT). Transcriptomic analysis of leaves, stems, main
      roots, and fibrous roots of P. zingiberensis was performed, and a total of 46,098
      unigenes were obtained, including all the identified homologous genes involved in
      ginsenoside biosynthesis. The most upstream genes were highly expressed in the
      leaves, and the UDP-glucosyltransferase genes were highly expressed in the roots.
      This finding indicated that the precursors of ginsenosides are mainly synthesized
      in the leaves and transported to different parts for the formation of particular
      ginsenosides. For the first time, enzyme activity assay characterized four genes
      (three from P. zingiberensis and one from P. japonicus var. major, another Panax
      species with oleanane-type ginsenosides) encoding OAGT, which particularly
      transfer glucuronic acid at C-3 of oleanolic acid to form oleanolic acid 3-O-beta
      glucuronide. Taken together, our study provides valuable genetic information for
      P. zingiberensis and the genes responsible for synthesizing the direct precursor
      of oleanane-type ginsenosides.

PMID- 30219961
TI  - Sleep quality in survivors of critical illness: practical shortcomings
      unresolved.

PMID- 30219962
TI  - Telmisartan attenuates kidney apoptosis and autophagy-related protein expression
      levels in an intermittent hypoxia mouse model.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is associated with renal impairs. As a
      novel pathophysiological hallmark of OSA, chronic intermittent hypoxia (CIH)
      enhances apoptosis and autophagy. The present study aims to evaluate the effect
      of telmisartan on CIH-induced kidney apoptosis and autophagy in a mouse model of
      OSA. MATERIALS AND METHODS: Mice were randomly allocated to normoxia, CIH, and
      CIH+telmisartan groups (n = 12 in each group). The CIH exposure duration was 12
      weeks. Mice in the CIH+telmisartan group received telmisartan administration. The
      terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and
      western blotting of Bax and cleaved caspase-3 were conducted for evaluating
      apoptosis in kidney tissue. While the autophagy-related proteins, beclin-1 and
      LC3, were also observed via western blotting. RESULTS: The percentage of
      apoptotic cell in the CIH group was significantly higher than that of normoxia
      group; meanwhile, Bax and cleaved caspase-3 protein levels were increased in the
      CIH group than those of normoxia group (all p < 0.05). Compared with the normoxia
      group, mice in the CIH group had greater autophagy-related proteins (beclin-1 and
      LC3) expression. When compared to the CIH group, both the renal apoptosis and
      autophagy in the CIH+telmisartan group were decreased. CONCLUSION: The CIH
      accelerates renal apoptosis and autophagy levels. Telmisartan ameliorating those
      levels suggests that it might prevent renal impairs from the CIH in OSA patients.

PMID- 30219965
TI  - Food insecurity and adult weight abnormality risk: a systematic review and meta
      analysis.
AB  - PURPOSE: Research into the relationship between food insecurity and weight
      abnormality has yielded varied and contradictory results. Therefore, a systematic
      review and meta-analysis were carried out to examine the association between food
      insecurity and weight abnormality in adults. METHODS: Pertinent studies were
      identified by searching PubMed and Scopus databases, up to February 2018. Data
      were available from 31 studies. These studies were conducted in 14 different
      countries. The odds ratio of 115,993 individuals in these studies was pooled for
      the meta-analysis. RESULTS: The present meta-analysis showed that adults in food
      insecure households are more at risk of obesity (OR 1.15, 95% CI 1.06-1.23).
      Subgroup analysis by gender also revealed that women had a higher risk of obesity
      compared to men in food-insecure households (OR 1.26, 95% CI 1.05-1.46).
      Furthermore, subgroup analysis by food insecurity level implied that a severe
      level of household food insecurity may be associated with a higher risk of
      underweight (49%) than overweight (37%) or obesity (29%) among adults. In
      addition, subgroup analysis revealed that with lower levels of national economic
      development, the risk of weight abnormality shifted from obesity to underweight.
      CONCLUSION: It seems that adults in food-insecure households, especially women,
      are at higher risk of obesity. The weight abnormality risk may increase with the
      intensification of the level of food insecurity. Also, the level of economic
      development is an important factor in the effects of food insecurity on weight
      status. However, due to the high heterogeneity among studies, the results should
      be interpreted with caution.

PMID- 30219963
TI  - FDG PET in response evaluation of bulky masses in paediatric Hodgkin's lymphoma
      (HL) patients enrolled in the Italian AIEOP-LH2004 trial.
AB  - PURPOSE: We present the results of an investigation of the role of FDG PET in
      response evaluation of bulky masses in paediatric patients with Hodgkin's
      lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial. METHODS: We analysed
      data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL
      and enrolled in 41 different Italian centres from March 2004 to September 2012,
      all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients
      with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after
      four cycles of chemotherapy. Responses were determined according to combined
      functional and morphological criteria. Patients were followed up for a mean
      period of 43 months and for each child we calculated time-to-progression (TTP)
      and relapse rates considering clinical monitoring, and instrumental and
      histological data as the reference standard. Statistical analyses were performed
      for FDG PET and morphological responses with respect to TTP. Multivariate
      analysis was used to define independent predictive factors. RESULTS: Overall,
      response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET
      positive patients (9.5%), with a significant difference in TTP between these
      groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive
      scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed
      a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6
      patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a
      significant difference in TTP between patients with CR and patients with PD (31.1
      months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there
      was a significant difference in relapse rates between PET-positive and PET
      negative patients (p = 0000). In patients with PR, there was also a significant
      difference in TTP between PET-positive and PET-negative patients (24.6 months and
      34.9 months, respectively; p < 0.0001). In the multivariate analysis with
      correction for multiple testing, only the PET result was an independent
      predictive factor in both the entire cohort of patients and the subgroup showing
      PR on CT (p < 0.01). CONCLUSION: After four cycles of chemotherapy, FDG PET
      response assessment in paediatric HL patients with a bulky mass is a good
      predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET
      was able to differentiate those with a longer TTP. In paediatric HL patients with
      a bulky mass and in patients with a PR on CT, response on FDG PET was an
      independent predictive factor.

PMID- 30219964
TI  - Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the
      localization of hyperfunctioning parathyroid glands and correlation with
      molecular profile.
AB  - PURPOSE: The localization of hyperfunctioning parathyroid gland(s) (HPTG) in
      patients with primary hyperparathyroidism (PHPT) with negative or inconclusive
      first-line imaging is a significant challenge. This study aimed to evaluate the
      role of integrated 18F-choline PET/4D contrast-enhanced computed tomography
      (4DCeCT) in these patients, compare its detection rate and sensitivity with those
      of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline
      metabolism and morphological, biochemical and molecular parameters of HPTG.
      METHODS: We prospectively enrolled 44 PHPT patients with negative or inconclusive
      first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same
      time, and integrated 18F-choline PET/4DCeCT images were obtained after
      coregistration. Experienced physicians examined the images. The SUVratio and
      degree of contrast enhancement were recorded for each positive finding.
      Histopathology, laboratory and multidisciplinary follow-up were used as the
      standard of reference. Both the detection rates and sensitivities of the three
      imaging modalities were calculated retrospectively. Immunohistochemistry was
      performed to evaluate the molecular profile of HPTGs. RESULTS: 18F-Choline
      PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%),
      and 31 of 31 surgically treated patients (sensitivity 100%). These results were
      significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%,
      respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant
      correlation between SUV and calcium level was found. In a multivariate analysis,
      only calcium level was significantly associated with 18F-choline PET/4DCeCT
      findings. SUVratio and Ki67 expression were significantly correlated. CONCLUSION:
      Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to
      detect PHPT in patients with negative or inconclusive first-line imaging. Choline
      metabolism is correlated with both calcium level and Ki67 expression in HPTG.

PMID- 30219966
TI  - Altering polymerization temperature of antibiotic-laden cement can increase
      porosity and subsequent antibiotic elution.
AB  - PURPOSE: To examine the role of polymerization temperature on the cement porosity
      and antibiotic elution to optimize antibiotic release from antibiotic-laden
      cement (ABLC). METHODS: Elution profiles of vancomycin and tobramycin from ABLC
      discs prepared with low- and high-dose antibiotic dosages, cured at 8, 21, and 37
      degrees C, and placed in phosphate buffered saline (PBS) at 37  degrees C were
      examined. Samples were collected at one, four, eight, 24, 72, 168, 336, and 1008
      hours to calculate the quantity of antibiotic eluted. Porosity was determined by
      MicroCT analysis. RESULTS: ABLC porosity and antibiotic elution were increased up
      to five times the amount eluted from room temperature discs (p < 0.05). Low-dose
      ABLC group saw decreased but similar porosity at 8  degrees C and 21  degrees C
      compared to cement cured at 37  degrees C (p < 0.001). High-dose ABLC group
      porosities were all significantly different (p < 0.02). CONCLUSIONS: Altering the
      polymerization temperature of ABLC led to more porous constructs yielding
      increased antibiotic elution.

PMID- 30219968
TI  - The effectiveness of robotic hip and knee arthroplasty on patient-reported
      outcomes: A systematic review and meta-analysis.
AB  - PURPOSE: The purpose of the study is to determine the effectiveness of semi
      active and active robotic hip and knee arthroplasty on post-operative patient
      reported outcomes of function, pain, quality of life and satisfaction with
      surgery. METHODS: PubMed, Medline, Embase and CENTRAL were searched. Included
      were comparative studies investigating the effectiveness of semi-active or active
      robotic hip or knee arthroplasty compared to any other surgical intervention on
      function, pain, quality of life and satisfaction with surgery. Risk of bias and
      the strength of the evidence were assessed using the Downs and Black tool and the
      GRADE system, respectively. Relative risks, mean differences and 95% CI were
      calculated using random-effects models. RESULTS: Fourteen studies involving 1342
      patients were included. All studies compared robotic to conventional surgery,
      with active robotic surgery evaluated in total hip or knee arthroplasty and semi
      active robotic surgery in total hip or unicompartmental knee arthroplasty. Most
      studies presented some risk of bias, and the strength of evidence was rated as
      low to very low quality. Random-effects meta-analyses showed that post-operative
      functional outcomes were comparable between active robotic and conventional total
      hip and knee arthroplasty at the short-, medium- and long-term follow-up. No
      significant difference in pain, quality of life and satisfaction with surgery
      were reported in individual studies. CONCLUSIONS: This systematic and meta
      analyses indicates that functional outcomes for patients undergoing active
      robotic total hip and knee arthroplasty were comparable to conventional surgery.
      Whether semi-active or active robotic hip or knee arthroplasty is effective in
      improving post-operative pain, quality of life and satisfaction with surgery is
      unclear. PROSPERO Registration Number: CRD42017059932.

PMID- 30219967
TI  - Bone morphogenetic proteins in fracture repair.
AB  - Bone fractures represent a significant medical morbidity among aged population
      with osteoporosis. Bone morphogenetic proteins (BMPs) are suggested to have
      therapeutic potential to enhance fracture healing in such patients. Though BMP
      mediated fracture healing has been well-documented in preclinical models, there
      has been no clinical study that demonstrated unequivocally that indeed a BMP when
      presented with an appropriate scaffold could provide basis for robust outcome for
      delayed or non-union diaphyseal bone fractures. This review presents a
      comprehensive insight towards the existing knowledge on the role of BMP signaling
      in bone formation and maintenance. Also therapeutic options based on BMP biology
      are discussed.A novel osteoinductive autologous bone graft substitute (ABGS)
      aimed to accelerate bone regeneration was developed and is currently being tested
      in the clinical setting. It comprises of a biologically compatible autologous
      carrier made from the patient's peripheral blood (autologous blood coagulum, ABC)
      and of rhBMP6 as an active ingredient. Such formulation circumvents the use of
      animal-derived materials, significantly limits inflammatory processes common in
      commercial bone devices and renders the carrier flexible, malleable, and
      injectable ensuring the ease of use. The ongoing clinical trials result will
      provide more detailed insights into the safety, tolerability, pharmacokinetics,
      and bone healing effects in humans and potentially provide novel and safe
      therapeutic options for bone repair.

PMID- 30219969
TI  - Connecting links between genetic factors defining ovarian reserve and recurrent
      miscarriages.
AB  - PURPOSE: Approximately 1-2% of the women faces three or more successive
      spontaneous miscarriages termed as recurrent miscarriage (RM). Many clinical
      factors have been attributed so far to be the potential risk factors in RM,
      including uterine anomalies, antiphospholipid syndrome, endocrinological
      abnormalities, chromosomal abnormalities, and infections. However, in spite of
      extensive studies, reviews, and array of causes known to be associated with RM,
      about 50% cases encountered by treating physicians remains unknown. The aims of
      this study were to evaluate recent publications and to explore oocyte-specific
      genetic factors that may have role in incidence of recurrent miscarriages.
      METHOD: Recent studies have identified common molecular factors contributing both
      in establishment of ovarian reserve and in early embryonic development. Also,
      studies have pointed out the relationship between the age-associated depletion of
      OR and increase in the risk of miscarriages, thus suggestive of an interacting
      biology. Here, we have gathered literature evidences in establishing connecting
      links between genetic factors associated with age induced or pathological OR
      depletion and idiopathic RM, which are the two extreme ends of female
      reproductive pathology. CONCLUSION: In light of connecting etiological link
      between infertility and RM as reviewed in this study, interrogating the oocyte
      specific genes with suspected roles in reproductive biology, in cases of
      unexplained RM, may open new possibilities in widening our understanding of RM
      pathophysiology.

PMID- 30219971
TI  - Integrating Storytelling into a Communication Skills Teaching Program for Medical
      Oncology Fellows.
AB  - Oncology training focuses primarily on biomedical content rather than
      psychosocial content, which is not surprising in light of the enormous volume of
      technical information that oncology fellows assimilate in a short time.
      Nonetheless, the human connection, and specifically communication skills, remains
      as important as ever in caring for highly vulnerable patients with cancer. We
      previously described a year-long communication skills curriculum for oncology
      fellows that consisted of monthly 1-hour seminars with role play as the
      predominant teaching method (Epner and Baile, Acad Med. 89:578-84, 2014). Over
      several years, we adapted the curriculum based on learner feedback and reflection
      by faculty and teaching assistants and consolidated sessions into quarterly 3-4
      hour workshops. We now describe integrating stories into the curriculum as a way
      of building empathy and warming fellows to the arduous task of dealing with
      highly emotional content, such as conversations with young patients about
      transitioning off disease-directed therapy. Learners read and discussed
      published, medically themed stories; discussed their own patient care stories;
      and completed brief writing reflections and discussions. They then worked in
      small groups facilitated by faculty and upper level fellows who functioned as
      teaching assistants to work on applying specific skills and strategies to
      scenarios that they chose. Fellows completed anonymous surveys on which they
      rated the curriculum highly for relevance, value, organization, content, and
      teaching methods, including storytelling aspects. We conclude that sharing
      stories can help highly technical learners build reflective ability, mindfulness,
      and empathy, which are all critical ingredients of the art of medicine.

PMID- 30219970
TI  - Mutational and copy number asset of primary sporadic neuroendocrine tumors of the
      small intestine.
AB  - Small intestine neuroendocrine tumors (SI-NETs) represent the most common
      histotype among small intestine neoplasms, and metastatic disease is usually
      present at diagnosis. A retrospective series of 52 sporadic primary surgically
      resected SI-NETs, which were metastatic at diagnosis, was analyzed by high
      coverage target sequencing (HCTS) for the mutational status of 57 genes and copy
      number status of 40 genes selected from recently published genome sequencing
      data. Seven genes were found to be recurrently mutated: CDKN1B (9.6%), APC and
      CDKN2C (each 7.7%), BRAF, KRAS, PIK3CA, and TP53 (each 3.8%). Copy number
      analysis showed frequent allelic loss of 4 genes located on chromosome 18 (BCL2,
      CDH19, DCC, and SMAD4) in 23/52 (44.2%) and losses on chromosomes 11 (38%) and 16
      (15%). Other recurrent copy number variations were gains for genes located on
      chromosomes 4 (31%), 5 (27%), 14 (36%), and 20 (20%). Univariate survival
      analysis showed that SRC gene copy number gains were associated with a poorer
      prognosis (p = 0.047). Recurrent copy number variations are important events in
      SI-NET and SRC may represent a novel prognostic biomarker for this tumor type.

PMID- 30219972
TI  - A case of intraductal papillary-mucinous neoplasm of the pancreas penetrating
      into the stomach and spleen successfully treated by total pancreatectomy.
AB  - BACKGROUND: Intraductal papillary-mucinous neoplasms (IPMNs) are potentially
      malignant intraductal epithelial neoplasms that sometimes penetrate into other
      organs. To the best of our knowledge, no report has yet described a case with
      penetration into the spleen. We recently encountered a case of IPMN with
      penetration of the stomach and spleen that was successfully treated by total
      pancreatectomy. CASE PRESENTATION: A 70-year-old female visited our hospital with
      a complaint of fever and abdominal pain. Contrast-enhanced computed tomography
      (CT) revealed dilatation of the main pancreatic duct in the entire pancreas and
      penetration into the stomach and spleen. Upper gastrointestinal endoscopy
      revealed mucin extruding from four openings of the fistula in the stomach. No
      malignancy was detected based on cytology of the mucin. Inflammation markers and
      tumor markers (CEA, CA19-9) were elevated in the blood. The pre-operative
      diagnosis was IPMN of main pancreatic duct type penetrating into the stomach and
      spleen. A total pancreatectomy and splenectomy were performed, combined with
      distal gastrectomy including resection of the fistulas between the pancreas and
      stomach. No postoperative complications were noted. Histopathological examination
      of the resected specimen revealed atrophy of the pancreatic parenchyma, and the
      main duct of the pancreas was filled with mucin. Mucin-producing malignant tumor
      cells were detected in the epithelium of the main pancreatic duct with no signs
      of invasion. No malignancy was found at the fistulas between the pancreas and
      stomach or spleen. The patient was finally diagnosed with non-invasive
      intraductal papillary-mucinous carcinoma (IPMC) of main pancreatic duct type.
      Mechanical penetration was suspected as a mechanism of the penetration. The
      patient remained disease-free without evidence of recurrence more than 15 months
      after the operation. CONCLUSION: Though IPMNs sometimes penetrate into other
      adjacent organs, penetration into two organs, including the spleen, is rare. The
      rare case of IPMC penetrating into the stomach and spleen presented here was
      treated successfully by total pancreatectomy.

PMID- 30219974
TI  - A quantitative analysis of global environmental protection values based on the
      world values survey data from 1994 to 2014.
AB  - The four most recent sub-datasets of the World Value Survey (WVS) database (i.e.,
      WVS3, WVS4, WVS5, and WVS6) contain a total of 25 non-numerical variables of
      environmental protection values and cover the period from 1994 to 2014. This
      study utilized these datasets to obtain the spatiotemporal distributions of the
      values and provided a preliminary analysis of the environmental protection values
      in different cultural districts. The work includes 4 parts. First, the
      information from the values included in the 25 variables is subjectively
      classified into action values and attitude values according to the meanings of
      the variable labels. Then, quantitative clustering is used to verify the results
      of the first step. These two steps consistently classify the 25 variables into
      "action" and "attitude" families. At the third step, all variables are processed
      as horizontal distributions in terms of the country using the arithmetic mean of
      the serial numbers chosen by the respondents because these numbers reflect the
      grade of the behavior or attitude toward environmental protection. A clustering
      procedure is also included in this step to reconfirm the classification results
      of the previous two steps. Finally, the two families are quantified using their
      common factors, which are the first leading modes of the empirical orthogonal
      function for each family. The multiyear averaged cultural district mean "action"
      and "attitude" indices are analyzed according to the World Culture Map. The
      results show that districts with different cultures have very different
      environmental protection values.

PMID- 30219973
TI  - A glassy carbon electrode modified with nitrogen-doped reduced graphene oxide and
      melamine for ultra-sensitive voltammetric determination of bisphenol A.
AB  - A composite was prepared at room temperature from nitrogen-doped reduced graphene
      oxide (N-rGO) and melamine via pi-interaction. An ultra-sensitive electrochemical
      sensor for the determination of trace levels of bisphenol A (BPA) was obtained by
      coating a glassy carbon electrode (GCE) with the composite. The structure and
      morphology of composite were characterized by FTIR, Raman, XRD, XPS, SEM and TEM.
      Because of the synergetic effects of N-rGO and melamine, the modified GCE
      displays considerably enhanced sensitivity to BPA. The voltammetric response,
      typically measured at a peak of 0.48 V (vs. SCE) is linear in the 0.05 to 20 MUM
      BPA concentration range, and the detection limit is 0.8 nM (at S/N = 3). The
      sensor is reproducible, stable and selective. It was applied to analyze baby
      bottles, drinking cups, mineral water bottles and shopping receipts that were
      spiked with BPA, and the recoveries reached 99.1-101.4%. Graphical abstract
      Illustration of fabricating the electrochemical sensor for detecting BPA. N-G/M:
      nitrogen-doped reduced graphene oxide and melamine composite; GCE: glassy carbon
      electrode.

PMID- 30219975
TI  - Microwave-assisted synthesis of thymine-functionalized graphitic carbon nitride
      quantum dots as a fluorescent nanoprobe for mercury(II).
AB  - A microwave-assisted hydrothermal method was employed to prepare thymine-modified
      graphitic carbon nitride quantum dots (T-gCNQDs) which are shown to be a novel
      fluorescent nanoprobe for Hg(II). They exhibit excellent optical properties (blue
      emission with a fluorescence quantum yield of 46%) and water solubility. The
      incorporation of thymine into the gCNQDs results in an enhancement in
      photoluminescence properties. It is found that fluorescence, best measured at
      excitation/emission wavelengths of 350/445 nm, is much more strongly quenched by
      Hg(II) compared to the thymine-free nanoprobe. The quenching is highly selective
      even in the presence other metal ions. This is ascribed to the formation of T
      Hg(II)-T base complexes. Fluorescence drops linearly in the 1.0 to 500 nM Hg(II)
      concentration range, and the limit of detection is 0.15 nM. The method was
      applied to the determination of Hg(II) in spiked samples of tap and pond water.
      Recoveries were found to be >95%, thus demonstrating the practical applicability
      of the assay. Graphical abstract A microwave-assisted hydrothermal route was
      employed to prepare thymine-functionalized graphitic carbon nitride QDs (T
      gCNQDs). A selective fluorescence quenching mechanism occurred between T-gCNQDs
      and Hg(II) due to thymine functionalization. T-gCNQDs was utilized to detect
      Hg(II) in real samples.

PMID- 30219976
TI  - Selective Forces Related to Spinocerebellar Ataxia Type 2.
AB  - Spinocerebellar ataxia type 2 (SCA2) is caused by an unstable expanded CAG repeat
      tract (CAGexp) at ATXN2. Although prone to selective forces such as anticipation,
      SCA2 frequency seems to be stable in populations. Our aim was to estimate
      reproductive success, segregation patterns, and role of anticipation in SCA2.
      Adult subjects from families with molecular diagnosis provided data about all
      his/her relatives. Affected and unaffected sibs older than 65.7 years of age were
      used to estimate reproductive success and segregation patterns. Twenty-one SCA2
      families were studied, including 1017 individuals (164 affected) who were born
      from 1840 to 2012. The median number of children of the non-carriers and
      carriers, among 99 subjects included in the reproductive success analysis, were 2
      and 3 (p < 0.025), respectively. Therefore, the reproductive success of carriers
      was 1.5. There were 137 non-carriers (59.6%) and 93 carriers (40.4%) (p = 0.04),
      among subjects included in the segregation analysis. Age at onset across
      generations pointed to anticipation as a frequent phenomenon. We raised evidence
      in favor of increased reproductive success related to the carrier state at ATXN2,
      and segregation distortion favoring normal alleles. Since majority of normal
      alleles analyzed carried 22 repeats, we propose that this distortion segregation
      can be related to the high frequency of this allele in human chromosomes.

PMID- 30219977
TI  - Examining the Role of and Treatment Directed at IL-1beta in Atherosclerosis.
AB  - PURPOSE: The purpose of this review was to examine the role of IL-1beta in the
      inflammatory process central to the development of atherosclerosis and to discuss
      current clinical evidence for treatments targeting IL-1beta in coronary artery
      disease. RECENT FINDINGS: IL-1beta has been shown to modulate atherosclerotic
      plaque progression by upregulating the synthesis of adhesion molecules on
      endothelial cells, as well increasing activation and proliferation of vascular
      smooth muscle cells. Animal studies have further suggested that alterations in
      the balance between agonists and antagonists of IL-1beta are important in
      promoting atherosclerosis. In humans, preliminary assessment of therapy targeting
      IL-1beta noted early reductions in serum inflammatory biomarkers among those with
      systemic inflammatory or coronary artery disease. The CANTOS trial, a large
      randomized double-blind study found that canakinumab, a monoclonal antibody
      targeting IL-1beta, reduced ischemic events in patients being treated for
      secondary prevention. Cellular, animal, and now clinical studies have suggested a
      role for therapies aimed at IL-1beta for treatment of CAD. However, given
      potential side effects and costs of these medications, further study is required
      to determine which patients may be most suited for treatment above current
      standard of care.

PMID- 30219978
TI  - Stool filling of an intestinal duplication cyst at the ileocecal valve triggers
      colonic intussusception: a case report.
AB  - BACKGROUND: Intestinal duplication, a congenital malformation, is considered a
      rare condition, particularly in adults. Although it affects young children, a
      minority of patients remains asymptomatic until adulthood. Here, we describe a
      case of an intestinal duplication cyst that caused intussusception by a unique
      mechanism. CASE PRESENTATION: A 19-year-old man was admitted to our hospital for
      intermittent abdominal pain. Computed tomography revealed colonic intussusception
      induced by a nodular mass in the ileocecal region. Urgent ileocecal resection was
      performed because of the risk of colonic ischemia. The resected material
      comprised a stool-filled noncommunicating cyst that protruded into the enteric
      lumen at the ileocecal valve. Histological analyses revealed that the inner wall
      of the cyst was lined with colonic mucosa and that the muscle layer of the cyst
      was shared with that of the original enteric wall; furthermore, the cyst had a
      vestige of an opening site in the wall. We concluded that the cyst was an
      intestinal duplication that poured stool into its lumen through the tiny orifice,
      thereby triggering intussusception. CONCLUSIONS: The present case suggests that
      stool-pouring can cause intussusception into the space of an intestinal
      duplication lesion.

PMID- 30219979
TI  - Phytofabricated silver nanoparticles of Phyllanthus emblica attenuated
      diethylnitrosamine-induced hepatic cancer via knock-down oxidative stress and
      inflammation.
AB  - Oxidative stress and inflammation play a pivotal role in the expansion and
      progression of hepatic cancer. Nanoparticle-based drug delivery can quickly
      enhance the restorative capability of hepatic cancer. Silver nanoparticles
      synthesized from plant source are of great importance due to their small size,
      economic, non-hazardous and different biomedical applications. In the current
      study, we have evaluated the impacts of oxidative stress and proinflammatory
      markers of biosynthesized silver nanoparticles of Phyllanthus emblica (PE) leaves
      against diethylnitrosamine-induced hepatocellular carcinoma (HCC) in wistar rats
      till 16 weeks with its underlying mechanism. The physico-chemical properties of
      biosynthesized silver nanoparticles were determined by ultra-visible
      spectroscopy, Fourier transform infrared spectroscopy, field emission scanning
      electron microscope, energy dispersive X-ray analysis, transmission electron
      microscopy and X-ray diffraction studies. Biofabricated silver nanoparticles
      (PEAgNPs) significantly enhanced the process of recovery from hepatic cancer in
      animal models, which was ascertained by increased body weight, reduced hepatic
      knobs on the outer surface of liver, downregulated serum biochemical parameters
      (ALT: 134.66 +/- 2.60; AST: 120.33 +/- 3.18; ALP: 153.33 +/- 4.25; AFP: 167.33 +/
      3.38), decreased hepatic lipid peroxidation (20.22 +/- 1.74), increased membrane
      bound enzymes (Na+/K+ATPase: 4.18 +/- 0.20; Ca2+ATPase: 6.24 +/- 0.12), increased
      antioxidants parameters (CAT: 64.89 +/- 4.13; SOD: 6.01 +/- 0.11; GPx: 8.55 +/-
      0.05), alteration in the level of proinflammatory cytokines (TNF-alpha: 90.15 +/-
      5.77; NF-kappaB: 173.29 +/- 7.26; IL-6: 178.11 +/- 3.16; IL-1beta: 48.26 +/-
      1.89) and histopathological studies. Our outcomes implicate successfully
      biofabrication of silver nanoparticles and exhibited a chemoprotective potential
      in the prevention and intervention of hepatocellular carcinoma.

PMID- 30219980
TI  - Dynamics of blood flow: modeling of Fahraeus and Fahraeus-Lindqvist effects using
      a shear-induced red blood cell migration model.
AB  - Blood flow in micro capillaries of diameter approximately 15-500 MUm is
      accompanied with a lower tube hematocrit level and lower apparent viscosity as
      the diameter decreases. These effects are termed the Fahraeus and Fahraeus
      Lindqvist effects, respectively. Both effects are linked to axial accumulation of
      red blood cells. In the present investigation, we extend previous works using a
      shear-induced model for the migration of red blood cells and adopt a model for
      blood viscosity that accounts for the suspending medium viscosity and local
      hematocrit level. For fully developed hematocrit profiles (i.e., independent of
      axial location), the diffusion fluxes due to particle collision frequency and
      viscosity gradients are of equal magnitude and opposite directions. The ratio of
      the diffusion coefficients for the two fluxes affects both the Fahraeus and
      Fahraeus-Lindqvist effects and is found related to the capillary diameter and
      discharge hematocrit using a well-known data-fit correlation for apparent blood
      viscosity. The velocity and hematocrit profiles were determined numerically as
      functions of radial coordinate, tube diameter, and discharge hematocrit. The
      velocity profile determined numerically is consistent with the derived analytical
      expression and the results are in good agreement with published numerical results
      and experimental data for hematocrit ratio and hematocrit and velocity profiles.

PMID- 30219981
TI  - Isolation and characterization of two lytic bacteriophages against Staphylococcus
      aureus from India: newer therapeutic agents against Bovine mastitis.
AB  - Bovine mastitis causes severe economic losses to dairy farmers. Staphylococcus
      aureus, is one of the most important pathogen implicated in etiology of clinical
      and subclinical mastitis in bovines. In view of increasing antimicrobial
      resistance alternatives to antibiotic therapy are much needed. The present decade
      has witnessed a renewed interest in phage based therapeutics and diagnostics. The
      present study, describes isolation and characterization of two lytic phages SAJK
      IND and MSP against Staphylococcus aureus having a potential to be used in
      therapy against mastitis. SAJK-IND and MSP phages belonged to Myoviridae and
      Podoviridae families, respectively. TEM imaging of the two phages revealed an
      iscosahedral head. MSP phage has a short non contractile tail. SAJK-IND and MSP
      have a burst size of 44 +/- 3 and 25 +/- 5 PFU/ infected cell, respectively. SAJK
      IND and MSP phages revealed  12 and 16 proteins, respectively on SDS-PAGE
      analysis. The lytic activity of the phages was specific for Staphylococcus
      aureus. SAJK-IND revealed 100% lytic activity against several strains of
      Staphylococcus aureus isolated from mastitis milk samples whereas, MSP had only
      40% lytic activity. SAJK-IND phage genome was sequenced, assembled and deposited
      in Genbank under accession no MG010123.

PMID- 30219983
TI  - Correction to: The Prevalence of Mental Illness and Substance Abuse Among Rural
      Latino Adults with Multiple Adverse Childhood Experiences in California.
AB  - The original version of this article unfortunately published without
      acknowledgement section. The complete funding information is given below.

PMID- 30219982
TI  - Gastric Cancer Screening in Common Variable Immunodeficiency.
AB  - Individuals with common variable immunodeficiency (CVID) have an increased risk
      of gastric cancer, and gastrointestinal lymphoma, yet screening for premalignant
      gastric lesions is rarely offered routinely to these patients. Proposed screening
      protocols are not widely accepted and are based on gastric cancer risk factors
      that are not applicable to all CVID patients. Fifty-two CVID patients were
      recruited for screening gastroscopy irrespective of symptoms or blood results and
      were compared to 40 controls presenting for gastroscopy for other clinical
      indications. Overall, 34% of CVID patients had intestinal metaplasia (IM),
      atrophic gastritis or moderate to severe non-atrophic gastritis, which can
      increase the risk of gastric cancer, compared to 7.5% of controls (p < 0.01).
      Focal nodular lymphoid hyperplasia, a precursor lesion for gastrointestinal
      lymphoma, was seen in eight CVID patients (16%), one of whom was diagnosed with
      gastrointestinal lymphoma on the same endoscopy. High-risk gastric pathology was
      associated with increased time since diagnosis of CVID, smoking, Helicobacter
      pylori, a low-serum pepsinogen I concentration, and diarrhea, but not pepsinogen
      I/II ratio, iron studies, vitamin B12 levels or upper gastrointestinal symptoms.
      There was a lower rate of detection of IM when fewer biopsies were taken, and IM
      and gastric atrophy were rarely predicted by the endoscopist macroscopically,
      highlighting the need for standardized biopsy protocols. The prevalence of
      premalignant gastric lesions in patients with CVID highlights the need for
      routine gastric screening. We propose a novel gastric screening protocol to
      detect early premalignant lesions and reduce the risk of gastric cancer and
      gastric lymphoma in these patients.

PMID- 30219985
TI  - Agreement between medical records and self-reports: Implications for transgender
      health research.
AB  - A key priority of transgender health research is the evaluation of long-term
      effects of gender affirmation treatment. Thus, accurate assessment of treatment
      receipt is critical. The data for this analysis came from an electronic medical
      records (EMR) based cohort of transgender individuals. A subset of cohort members
      were also asked to complete a self-administered survey. Information from the EMR
      was compared with survey responses to assess the extent of agreement regarding
      transmasculine (TM)/transfeminine (TF) status, hormone therapy receipt, and type
      of surgery performed. Logistic regression models were used to assess whether
      participant characteristics were associated with disagreement between data
      sources. Agreement between EMR and survey-derived information was high regarding
      TM/TF status (99%) and hormone therapy receipt (97%). Lower agreement was
      observed for chest reconstruction surgery (72%) and genital reconstruction
      surgery (84%). Using survey responses as the "gold standard", both chest and
      genital reconstruction surgeries had high specificity (95 and 93%, respectively),
      but the corresponding sensitivities were low (49 and 68%, respectively). A lower
      proportion of TM had concordant results for chest reconstruction surgery (64%
      versus 79% for TF) while genital reconstruction surgery concordance was lower
      among TF (79% versus 89% for TM). For both surgery types, agreement was highest
      among the youngest participants. Our findings offer assurance that EMR-based data
      appropriately classify cohort participants with respect to their TM/TF status or
      hormone therapy receipt. However, current EMR data may not capture the complete
      history of gender affirmation surgeries. This information is useful in future
      studies of outcomes related to gender affirming therapy.

PMID- 30219984
TI  - Fertility preservation options in transgender people: A review.
AB  - Gender affirming procedures adversely affect the reproductive potential of
      transgender people. Thus, fertility preservation options should be discussed with
      all transpeople before medical and surgical transition. In transwomen, semen
      cryopreservation is typically straightforward and widely available at fertility
      centers. The optimal number of vials frozen depends on their reproductive goals
      and treatment options, therefore a consultation with a fertility specialist is
      optimal. Experimental techniques including spermatogonium stem cells (SSC) and
      testicular tissue preservation are technologies currently under development in
      prepubertal individuals but are not yet clinically available. In transmen, embryo
      and/or oocyte cryopreservation is currently the best option for fertility
      preservation. Embryo cryopreservation requires fertilization of the transman's
      oocytes with a donor or partner's sperm prior to cryopreservation, but this
      limits his future options for fertilizing the eggs with another partner or donor.
      Oocyte cryopreservation offers transmen the opportunity to preserve their
      fertility without committing to a male partner or sperm donor at the time of
      cryopreservation. Both techniques however require at least a two-week treatment
      course, egg retrieval under sedation and considerable cost. Ovarian tissue
      cryopreservation is a promising experimental method that may be performed at the
      same time as gender affirming surgery but is offered in only a limited amount of
      centers worldwide. In select places, this method may be considered for
      prepubertal children, adolescents, and adults when ovarian stimulation is not
      possible. Novel methods such as in-vitro activation of primordial follicles, in
      vitro maturation of immature oocytes and artificial gametes are under development
      and may hold promise for the future.

PMID- 30219986
TI  - The SSRI citalopram increases the sensitivity of the human circadian system to
      light in an acute dose.
AB  - RATIONALE: Disturbances of the circadian system are common in depression. Though
      they typically subside when depression is treated with antidepressants, the
      mechanism by which this occurs is unknown. Despite being the most commonly
      prescribed class of antidepressants, the effect of selective serotonin reuptake
      inhibitors (SSRIs) on the human circadian clock is not well understood.
      OBJECTIVE: To examine the effect of the SSRI citalopram (30 mg) on the
      sensitivity of the human circadian system to light. METHODS: This study used a
      double-blind, placebo-controlled, within-subjects, crossover design. Participants
      completed two melatonin suppression assessments in room level light (~ 100 lx),
      taking either a single dose of citalopram 30 mg or a placebo at the beginning of
      each light exposure. Melatonin suppression was calculated by comparing placebo
      and citalopram light exposure conditions to a dim light baseline. RESULTS: A 47%
      increase in melatonin suppression was observed after administration of an acute
      dose of citalopram, with all participants showing more suppression after
      citalopram administration (large effect, d = 1.54). Further, melatonin onset
      occurred later under normal room light with citalopram compared to placebo.
      CONCLUSIONS: Increased sensitivity of the circadian system to light could assist
      in explaining some of the inter-individual variability in antidepressant
      treatment responses, as it is likely to assist in recovery in some patients,
      while causing further disruption for others.

PMID- 30219987
TI  - Promoter variations in a homeobox gene, BnA10.LMI1, determine lobed leaves in
      rapeseed (Brassica napus L.).
AB  - KEY MESSAGE: BnA10.LMI1 positively regulates the development of leaf lobes in
      Brassica napus, and cis-regulatory divergences cause the different allele
      effects. Leaf shape is an important agronomic trait, and large variations in this
      trait exist within the Brassica germplasm. The lobed leaf is a unique
      morphological characteristic for Brassica improvement. Nevertheless, the
      molecular basis of leaf lobing in Brassica is poorly understood. Here, we show
      that an incompletely dominant locus, BnLLA10, is responsible for the lobed-leaf
      shape in rapeseed. A LATE MERISTEM IDENTITY1 (LMI1)-like gene (BnA10.LMI1)
      encoding an HD-Zip I transcription factor is the causal gene underlying the
      BnLLA10 locus. Sequence analysis of parental alleles revealed no sequence
      variations in the coding sequences, whereas abundant variations were identified
      in the regulatory region. Consistent with this finding, the expression levels of
      BnLMI1 were substantially elevated in the lobed-leaf parent compared with its
      near-isogenic line. The knockout mutations of BnA10.LMI1 gene were induced using
      the CRISPR/Cas9 system in both HY (the lobed-leaf parent) and J9707 (serrated
      leaf) genetic backgrounds. BnA10.LMI1 null mutations in the HY background were
      sufficient to produce unlobed leaves, whereas null mutations in the J9707
      background showed no obvious changes in leaf shape compared with the control.
      Collectively, our results indicate that BnA10.LMI1 positively regulates the
      development of leaf lobes in B. napus, with cis-regulatory divergences causing
      the different allelic effects, providing new insights into the molecular
      mechanism of leaf lobe formation in Brassica crops.

PMID- 30219988
TI  - Metabolism as master of hematopoietic stem cell fate.
AB  - HSCs have a fate choice when they divide; they can self-renew, producing new
      HSCs, or produce daughter cells that will mature to become committed cells.
      Technical challenges, however, have long obscured the mechanics of these choices.
      Advances in flow-sorting have made possible the purification of HSC populations,
      but available HSC-enriched fractions still include substantial heterogeneity, and
      single HSCs have proven extremely difficult to track and observe. Advances in
      single-cell approaches, however, have led to the identification of a highly
      purified population of hematopoietic stem cells (HSCs) that make a critical
      contribution to hematopoietic homeostasis through a preference for self-renewing
      division. Metabolic cues are key regulators of this cell fate choice, and the
      importance of controlling the population and quality of mitochondria has recently
      been highlighted to maintain the equilibrium of HSC populations. Leukemic cells
      also demand tightly regulated metabolism, and shifting the division balance of
      leukemic cells toward commitment has been considered as a promising therapeutic
      strategy. A deeper understanding of precisely how specific modes of metabolism
      control HSC fate is, therefore, of great biological interest, and more
      importantly will be critical to the development of new therapeutic strategies
      that target HSC division balance for the treatment of hematological disease.

PMID- 30219989
TI  - The value of different 18F-FDG PET/CT baseline parameters in risk stratification
      of stage I surgical NSCLC patients.
AB  - OBJECTIVE: Administration of postoperative chemotherapy to patients with
      completely resected stage I NSCLC is still a matter of debate. The aim of the
      present study was to evaluate the value of different baseline 18F-FDG PET
      parameters in identifying surgical stage I NSCLC patients who are at high risk of
      recurrence, and thus are indicated for further postoperative treatment. METHODS:
      This is a retrospective study, which included 49 patients (28 males, 21 females)
      with the median age of 69 years (range 28-84), who had pathologically proven
      stage I NSCLC. All patients underwent 18F-FDG PET/CT at baseline followed by
      complete surgical resection of the tumor (R0). Baseline SUVmax, MTV and TLG were
      measured. Patients' follow-up records were retrospectively reviewed, and DFS
      (disease-free survival) was assessed. For each parameter, the most accurate cut
      off value for the prediction of recurrence was calculated using the ROC curve
      analysis and the Youden index. DFS was evaluated for patients above and below the
      calculated cut-off value using the Kaplan-Meier method and the difference in
      survival between the two groups was estimated using the log-rank test. RESULTS:
      Median observation time of the patients after surgery was 28.7 months (range 3.5
      58.8 months). 9 patients developed recurrence. The calculated cut-off values for
      SUVmax, MTV and TLG were 6, 6.6 and 33.6, respectively. Using these cut-offs, the
      observed sensitivity for SUVmax, MTV and TLG for prediction of recurrence was
      100%, 89% and 89%, respectively, while the observed specificity was 43%, 73% and
      65%, respectively. The difference in survival between patients below and above
      the cut-off value was statistically significant in all three studied parameters.
      The highest AUC was observed for MTV (AUC = 0.825, p = 0.003), followed by TLG
      (AUC = 0.789, p = 0.007), and lastly SUVmax (AUC = 0.719, p = 0.041). ROC curve
      analysis showed that volumetric parameters had better predictive performance than
      SUVmax as regards recurrence. CONCLUSION: PET-derived parameters at baseline were
      predictive of recurrence in stage I surgical NSCLC patients. Moreover, the
      metabolic volume of the tumor was the most significant parameter for this purpose
      among the studied indices.

PMID- 30219990
TI  - Comparison of 18F-Choline PET/CT and MRI functional parameters in prostate
      cancer.
AB  - AIM: 18F-Choline (FCH) uptake parameters are strong indicators of aggressive
      disease in prostate cancer. Functional parameters derived by magnetic resonance
      imaging (MRI) are also correlated to aggressive disease. The aim of this work was
      to evaluate the relationship between metabolic parameters derived by FCH PET/CT
      and functional parameters derived by MRI. MATERIALS AND METHODS: Fourteen
      patients with proven prostate cancer who underwent FCH PET/CT and multiparametric
      MRI were enrolled. FCH PET/CT consisted in a dual phase: early pelvic list-mode
      acquisition and late whole-body acquisition. FCH PET/CT and multiparametric MRI
      examinations were registered and tumoral volume-of-interest were drawn on the
      largest lesion visualized on the apparent diffusion coefficient (ADC) map and
      projected onto the different multiparametric MR images and FCH PET/CT images.
      Concerning the FCH uptake, kinetic parameters were extracted with the best model
      selected using the Akaike information criterion between the one- and two-tissue
      compartment models with an imaging-derived plasma input function. Other FCH
      uptake parameters (early SUVmean and late SUVmean) were extracted. Concerning
      functional parameters derived by MRI scan, cell density (ADC from diffusion
      weighting imaging) and vessel permeability (Ktrans and Ve using the Tofts
      pharmakinetic model from dynamic contrast-enhanced imaging) parameters were
      extracted. Spearman's correlation coefficients were calculated to compare
      parameters. RESULTS: The one-tissue compartment model for kinetic analysis of PET
      images was selected. Concerning correlation analysis between PET parameters, K1
      was highly correlated with early SUVmean (r = 0.83, p < 0.001) and moderately
      correlated with late SUVmean (r = 0.66, p = 0.010) and early SUVmean was highly
      correlated with late SUVmean (r = 0.90, p < 0.001). No significant correlation
      was found between functional MRI parameters. Concerning correlation analysis
      between PET and functional MRI parameters, K1 (from FCH PET/CT imaging) was
      moderately correlated with Ktrans (from perfusion MR imaging) (r = 0.55, p =
      0.041). CONCLUSIONS: No significant correlation was found between FCH PET/CT and
      multiparametric MRI metrics except FCH influx which is moderately linked to the
      vessel permeability in prostate cancer.

PMID- 30219991
TI  - Patient Diversity and Population Health-Related Cardiovascular Outcomes
      Associated with Warfarin Use in Atrial Fibrillation: An Analysis Using
      Administrative Claims Data.
AB  - INTRODUCTION: Anticoagulants are effective for stroke prevention in atrial
      fibrillation (AF). Data on population health-related cardiovascular outcomes by
      race/ethnicity and gender are not well described. The aim was to assess the
      impact of patient diversity on associated cardiovascular outcomes related to
      warfarin anticoagulation in Medicare beneficiaries with AF. METHODS: Medicare
      administrative claims data for years 2000-2010 were used to calculate AF
      prevalence and rates of new AF cases. Three 20% sample cohorts of new AF
      beneficiaries for years 2000, 2005, and 2007 were extracted and analyzed in a
      longitudinal study design. The impact of warfarin on associated cardiovascular
      outcomes was measured with respect to race/ethnicity and gender. Measured
      outcomes included the risk of stroke, mortality and hospitalization after
      adjusting for age, gender, race/ethnicity, CHADS2 score and warfarin. RESULTS: AF
      prevalence and warfarin use increased while stroke and mortality rates declined
      across race/ethnicity and gender from 2000 to 2010. Analyses comparing Whites to
      non-Whites highlighted several disparities: (1) Blacks were 40% (p < 0.0001) more
      likely to have a stroke even after adjustment for warfarin; (2) in 2007,
      Hispanics had a 35% (p < 0.01) higher prevalence of stroke and warfarin did not
      reduce the risk; and (3) Asians had better outcomes. Warfarin reduced stroke less
      well in women who had a lower risk of death and hospitalization. Despite a > 70%
      (p < 0.0001) reduction in mortality for warfarin users, Blacks had a 25% (p <
      0.0001) higher mortality risk than Whites. CONCLUSIONS: Differences in population
      health metrics across race/ethnicity and gender exist in AF. Across all metrics,
      Blacks had comparatively worse outcomes. Patient diversity should be a focus for
      future investigations in AF to improve outcomes in the whole population. FUNDING:
      National Minority Quality Forum.

PMID- 30219992
TI  - The effect of H3O+ on the membrane morphology and hydrogen bonding of a
      phospholipid bilayer.
AB  - At the 2017 meeting of the Australian Society for Biophysics, we presented the
      combined results from two recent studies showing how hydronium ions (H3O+)
      modulate the structure and ion permeability of phospholipid bilayers. In the
      first study, the impact of H3O+ on lipid packing had been identified using
      tethered bilayer lipid membranes in conjunction with electrical impedance
      spectroscopy and neutron reflectometry. The increased presence of H3O+ (i.e.
      lower pH) led to a significant reduction in membrane conductivity and increased
      membrane thickness. A first-order explanation for the effect was assigned to
      alterations in the steric packing of the membrane lipids. Changes in packing were
      described by a critical packing parameter (CPP) related to the interfacial area
      and volume and shape of the membrane lipids. We proposed that increasing the
      concentraton of H3O+ resulted in stronger hydrogen bonding between the phosphate
      oxygens at the water-lipid interface leading to a reduced area per lipid and
      slightly increased membrane thickness. At the meeting, a molecular model for
      these pH effects based on the result of our second study was presented. Multiple
      MUs-long, unrestrained molecular dynamic (MD) simulations of a
      phosphatidylcholine lipid bilayer were carried out and showed a concentration
      dependent reduction in the area per lipid and an increase in bilayer thickness,
      in agreement with experimental data. Further, H3O+ preferentially accumulated at
      the water-lipid interface, suggesting the localised pH at the membrane surface is
      much lower than the bulk bathing solution. Another significant finding was that
      the hydrogen bonds formed by H3O+ ions with lipid headgroup oxygens are, on
      average, shorter in length and longer-lived than the ones formed in bulk water.
      In addition, the H3O+ ions resided for longer periods in association with the
      carbonyl oxygens than with either phosphate oxygen in lipids. In summary, the MD
      simulations support a model where the hydrogen bonding capacity of H3O+ for
      carbonyl and phosphate oxygens is the origin of the pH-induced changes in lipid
      packing in phospholipid membranes. These molecular-level studies are an important
      step towards a better understanding of the effect of pH on biological membranes.

PMID- 30219993
TI  - Uric Acid Treatment After Stroke Prevents Long-Term Middle Cerebral Artery
      Remodelling and Attenuates Brain Damage in Spontaneously Hypertensive Rats.
AB  - Hypertension is the most important modifiable risk factor for stroke and is
      associated with poorer post-stroke outcomes. The antioxidant uric acid is
      protective in experimental normotensive ischaemic stroke. However, it is unknown
      whether this treatment exerts long-term protection in hypertension. We aimed to
      evaluate the impact of transient intraluminal middle cerebral artery (MCA)
      occlusion (90 min)/reperfusion (1-15 days) on brain and vascular damage
      progression in adult male Wistar-Kyoto (WKY; n = 36) and spontaneously
      hypertensive (SHR; n = 37) rats treated (i.v./120 min post-occlusion) with uric
      acid (16 mg kg-1) or vehicle (Locke's buffer). Ischaemic brain damage was
      assessed longitudinally with magnetic resonance imaging and properties of MCA
      from both hemispheres were studied 15 days after stroke. Brain lesions in WKY
      rats were associated with a transitory increase in circulating IL-18 and
      cerebrovascular oxidative stress that did not culminate in long-term MCA
      alterations. In SHR rats, more severe brain damage and poorer neurofunctional
      outcomes were coupled to higher cortical cerebral blood flow at the onset of
      reperfusion, a transient increase in oxidative stress and long-lasting stroke
      induced MCA hypertrophic remodelling. Thus, stroke promotes larger brain and
      vascular damage in hypertensive rats that persists for long-time. Uric acid
      administered during early reperfusion attenuated short- and long-term brain
      injuries in both normotensive and hypertensive rats, an effect that was
      associated with abolishment of the acute oxidative stress response and prevention
      of stroke-induced long-lasting MCA remodelling in hypertension. These results
      suggest that uric acid might be an effective strategy to improve stroke outcomes
      in hypertensive subjects.

PMID- 30219995
TI  - Study of human radius construction systematics: evaluation by DXA in dry bone.
AB  - This study has been undertaken in order to describe the bone mass distribution of
      the dry human radius via dual x-ray absorptiometry (DXA) with a Norland XR-800
      densitometer machine. A sample of 39 dry radius bones was used. Two projections
      were made: antero-posterior and lateral, and five regions of interest were
      selected. The bone densities and the bone mineral contents of the various regions
      of the radius in the two projections were compared using Student's t tests for
      paired samples, with statistically significant differences being found in all of
      the values, except in the proximal extremity (P Ext). The area of greatest bone
      mineral content (BMC) was the medial diaphysis (M Diaph), followed by the distal
      extremity (D Ext), with the lowest value being found in the proximal extremity (P
      Ext). As for bone mineral density (BMD), a great symmetry is observed if we take
      the mean point of the longitudinal axis as a reference, with it being distributed
      from highest to lowest from the central part to the extremities. A correlation
      study of the BMD and BMC values between the segments themselves and with the
      total, in both positions, provides us with a high correlation (p <= 0.01), with
      the highest correlation value being found for the proximal diaphysis (P Diaph)
      region, indicating the heterogeneous nature of the distribution of the radius
      bone mass. Bone densitometry via DXA is useful in order to establish an overview
      of the structural construction of the human radius.

PMID- 30219994
TI  - Capsule endoscopy findings for the diagnosis of Crohn's disease: a nationwide
      case-control study.
AB  - BACKGROUND: Capsule endoscopy can be used to identify the early stage of small
      bowel Crohn's disease (CD). We evaluated significant small bowel capsule
      endoscopy (SBCE) findings that can lead to early diagnosis of CD. METHODS: We
      retrospectively accumulated clinical and SBCE data of 108 patients (63 with and
      45 without CD). Types of small bowel mucosal injuries, including erosion,
      ulceration, and cobblestone appearance, and the alignment of diminutive lesions
      were compared between patients with and without CD. Inter- and intra-observer
      agreement in the determination of lesions was assessed in 25 pairs of SBCE from
      the two groups. RESULTS: Under SBCE, cobblestone appearance (33% vs. 2%, p <
      0.0001), longitudinal ulcers (78% vs. 20%, p < 0.0001), and irregular ulcers (84%
      vs. 60%, p < 0.01) were more frequently found in patients with CD. Linear erosion
      (90% vs. 38%, p < 0.0001) and irregular erosion (89% vs. 64%, p < 0.005) were
      also more frequent in patients with CD. Furthermore, circumferential (75% vs. 9%,
      p < 0.0001) and longitudinal (56% vs. 7%, p < 0.0001) alignment of diminutive
      lesions, mainly observed in the 1st tertile of the small bowel, was more frequent
      in patients with CD. Good intra-observer agreement was found for ulcers,
      cobblestone appearance, and lesion alignment. However, inter-observer agreement
      of SBCE findings differed among observers. CONCLUSIONS: Circumferential or
      longitudinal alignment of diminutive lesions, especially in the upper small
      bowel, may be a diagnostic clue for CD under SBCE, while inter-observer
      variations should be cautiously considered when using SBCE.

PMID- 30219996
TI  - Should orthopedic surgeons consider reducing the negative effects of Outerbridge
      grade 2 patellofemoral chondral lesion on early postoperative recovery during
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to comparatively evaluate the
      effectiveness of intra-articular PRP and HA injections applied as the treatment
      of Outerbridge grade 2 chondral lesions in patellofemoral joint during
      arthroscopic ACL reconstruction. METHODS: The clinical and radiographic data of
      61 patients between 18 and 45 years of age were evaluated. The patients were
      separated into three groups. Hyaluronic acid injection was applied in 22 knees
      (Group 1), PRP injection was applied in 18 knees (Group 2), and 21 knees did not
      have any specific treatment except ACL reconstruction (Group 3). All patients
      were followed clinically at least for 12 months. Clinical examination of the
      operated knee, visual analogue scale (VAS) score, Lysholm knee score, and Tegner
      activity scale were the outcome measures. Routine X-ray and MRI were also
      performed for all patients at 12-month postoperative follow-up visit. RESULTS:
      Although the mean VAS and Lysholm scores at 3-month follow-up were better in
      Group 1 and 2 than Group 3, the efficacy of intra-articular PRP on healing
      process regarding progression of the mean VAS and Lysholm scores through 6- and
      12-month follow-ups was significantly better and longer than HA. No statistically
      significant differences were detected according to Tegner activity scale between
      the groups at 3 and 6 months; however, Group 2 had better activity level than
      both Group 1 (p < 0.001) and 3 (p < 0.001) at the end of 12 months after surgery.
      CONCLUSION: Intra-articular PRP injection applied as the treatment of concomitant
      Outerbridge grade 2 chondral lesion in patellofemoral joint during ACL
      reconstruction revealed better and durable clinical outcomes via decreasing the
      potentially negative effects of chondral pathology on postoperative healing with
      respect to HA injection. LEVEL OF EVIDENCE: III-retrospective comparative study.

PMID- 30219997
TI  - Impact of crossing Fayoumi and Leghorn chicken breeds on immune response against
      Newcastle disease virus vaccines.
AB  - This study was conducted to evaluate the immune response against Newcastle
      disease (ND) virus vaccines (live attenuated and inactivated) in purebred Lohman
      Selected Leghorn (LSL), Fayoumi, male Fayomi * female LSL (FL crossbred), male
      LSL * female Fayomi (LF reciprocal crossbred) chickens. One-hundred-day-old
      chicks of each genetic type were assigned to five equal replicates. The log
      geometric means of the hemagglutination inhibition (HI) antibody titers were
      calculated. The FL crossbred chickens had a significantly higher HI antibody
      titer at day 26 of age when compared with the LSL chickens (P = 0.039). The
      Fayoumi and FL crossbred chickens had significantly higher HI antibody titers at
      day 45 of age (2.35 and 2.23, respectively) when compared with the LSL chickens
      (P = 0.031). In the same way, the purebred Fayoumi and FL crossbred chickens had
      significantly higher HI antibody titers at 60 and 75 days of age (P = 0.009 and
      0.041, respectively) when compared with the purebred LSL and LF crossbred
      chickens. The LSL chickens showed a significantly higher (P < 0.05) correlation
      estimate between HI titer to the ND vaccine on day 75 of age and body weight at
      week 12 of age. When challenged with the virulent ND virus, the hazard ratio (HR)
      for mortality rates in purebred LSL and LF crossbred chickens were significantly
      (HR = 3.52 and 2.07; P = 0.001 and 0.049, respectively) higher than the Fayoumi
      chickens. In conclusion, purebred Fayoumi and FL crossbred chickens showed
      superior antibody titers against live attenuated and inactivated ND virus
      vaccines. Hence, Fayoumi breed may be incorporated in the crossbreeding programs
      to improve the genetic resistance to ND.

PMID- 30219998
TI  - Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite following
      intravenous administration in cattle.
AB  - This study investigated the pharmacokinetics of pentoxifylline (PTX) and its 5
      hydroxyhexyl metabolite (M-I) after single-dose intravenous (IV) administration
      (10 mg/kg) of PTX in six healthy cattle. The safety of PTX was evaluated by
      clinical observation and biochemical analysis. Plasma concentrations of PTX and M
      I were simultaneously determined by reverse-phase high performance liquid
      chromatography. Pharmacokinetic parameters were calculated using non
      compartmental methods. Salivation and discomfort were observed for 2 h following
      the drug administration. Serum direct bilirubin, total bilirubin, and phosphorus
      levels at 24 h following the drug administration were significantly different
      from the control values (0 h) (P < 0.05). Pharmacokinetic variables of PTX were
      characterized by a short terminal elimination half-life (1.05 +/- 0.19 h), a
      large volume of distribution (6.30 +/- 1.76 L/kg), and high total body clearance
      (5.31 +/- 1.27 L/h/kg). The mean ratio between the area under the concentration
      time curves of M-I and PTX was 1.34. These results indicate that single-dose
      administration of PTX at 10 mg/kg IV in cattle resulted in therapeutic
      concentrations similar to those observed in humans and horse. However, further
      studies are necessary to determine the safety and pharmacokinetics following
      repeated administrations of PTX.

PMID- 30219999
TI  - Risk factors of brucellosis (re-)incidence in sheep and goat flocks in an endemic
      area of Portugal.
AB  - This study aimed to determinate the main risk factors of brucellosis recurrence
      or highest animal incidence in flocks, under pastoralism, in an endemic area of
      Northeast Portugal. An epidemiological survey was performed on 25 recurrent (n =
      18) or highest seropositive (n = 7) sheep and mixed goat flocks and 19 historical
      (>= 10 years) brucellosis-free flock, between 2014 and 2017, within the same
      epidemiological area presenting an average annual incidence around 6%. According
      to the multivariable logistic model (P < 0.001), the lack of neighboring
      brucellosis-free flocks (odds ratio OR = 7.79; CI % 1.49-65.06), the occurrence
      of more than 50% of lambing or kidding in common paths and pastures (OR = 24.17;
      CI % 3.0-606.54), and the animal replacement with Rev.1 non-vaccinated young
      animals (OR = 18.47; CI % 2.54-408.21) were the causes that influence the
      recurrence and highest animal incidence in flocks. In extensive production
      systems, the confinement of the peri-parturient and the small ruminant
      replacement with Rev.1 vaccinated young females seems to play a major role on
      brucellosis control and eradication.

PMID- 30220000
TI  - Arthroscopic anatomy of the middle glenohumeral ligament.
AB  - PURPOSE: The middle glenohumeral ligament (MGHL) has seldom been studied and its
      function is unknown. The aim of this study was to describe its anatomical
      presentations. METHODS: A prospective study was conducted of MGHL anatomy in 107
      arthroscopies, with a description of its shape and superior and inferior
      insertion in the articular surface of the subscapularis tendon. The MGHL was
      investigated dynamically during internal rotation of the glenohumeral joint.
      RESULTS: Sixty-three percent (68/107) of the MGHLs were found to be leaf-like,
      and 27% (28/107) cord-like, 5.5% (6/107) vestigial, and 2% (2/107) had several
      strands. The MGHL was absent for 2% of patients (2/107). The inferior insertion
      point of the MGHL was lateral, masked by the humeral head, in 34% of cases
      (36/105), intermediate, in front of the glenohumeral joint line, in 57% of cases
      (60/105), and medial, in front of the labrum, in 9% of cases (9/105). During
      internal rotation, 46% (48/105) of the MGHLs were observed to retract medially,
      the subscapularis tendon moving away from the anterior glenoid rim, while 54%
      (57/105) remained visible in front of the glenohumeral joint and came into
      contact with the articular surface of the subscapularis tendon. CONCLUSIONS: The
      MGHL has many anatomical variations.

PMID- 30220001
TI  - Association between TLR4 polymorphisms (896 A>G, 1196 C>T, - 2570 A>G, - 2081
      G>A) and virulence factors in uropathogenic Escherichia coli.
AB  - Escherichia coli is the main etiological agent of urinary tract infections. Its
      virulence factors are important during the initial interaction stage with the
      host as they enable colonization of urinary tract tissues. The genetic markers
      evidencing susceptibility to develop recurrent infections have been previously
      described. Toll-like receptors are critical sensors of microbial attacks, and
      they are also effectors of the individual's innate defense for elimination of
      pathogens. The aim of this study was to evaluate the association between
      functional polymorphisms (896 A>G, 1196 C>T, - 2570 A>G, - 2081 G>A) and
      susceptibility to develop urinary tract infections as well as E. coli virulence
      factors. This study includes 100 samples from patients diagnosed with UTI and 100
      samples from uninfected subjects. A conventional urine culture was performed and
      the isolates were identified by using the Vitek automated system. TLR4 gene
      polymorphisms were identified by the PCR-RFLP technique. The hlyA, fimH, papC,
      iutA and cnf1 virulence factors as well as the E. coli phylogenetic group were
      assessed by PCR. In this study, it was observed that the presence of the - 2570
      polymorphism represents a risk of UTI (p < 0.01), whereas - 2081 confers
      protection (p < 0.01). The 896A>G and 1196C>T polymorphisms were associated with
      the E. coli virulence factors fimH and hlyA, respectively (p < 0.05). The B2
      group was the most frequent in clinical isolates (51%), and it displayed more
      virulence factors regarding other phylogenetic groups (p <= 0.05). An interesting
      finding was that strains considered as commensals, belonging to groups A and B1,
      can cause UTI and present virulence factors. Polymorphisms occurring in the TLR4
      promoter region are correlated with susceptibility or risk of UTI, whereas
      structural polymorphisms are associated with the recognition of virulence factors
      displayed by E. coli.

PMID- 30220003
TI  - Aptamer based voltammetric patulin assay based on the use of ZnO nanorods.
AB  - The authors describe an aptamer based assay for the mycotoxin patulin (PAT). A
      gold electrode was modified with a composite made from ZnO nanorods (ZnO-NRs) and
      chitosan. The ZnO-NRs was prepared by reaction with ammonia and subsequent
      hydrothermal growth. Its properties were characterized by X-ray diffraction,
      Raman spectroscopy and scanning electron microscopy. Subsequently, thiol-modified
      aptamers were self-assembled on AuNPs that had been electrodeposited on the
      surface of the modified electrode. The presence of ZnO-NRs on the electrode
      increases the loading with AuNPs and aptamers. It also warrants a relatively
      stable microenvironment for the aptamers. In the presence of PAT, it will form a
      complex with the aptamer on the electrode surface. This hinders electron transfer
      from the electrode to the redox probe hexacyanoferrate and results in reduced
      current, which is typically measured at 0.176 V (vs. Ag/AgCl). The concentration
      of PAT can be calculated from the differences in the peak current before and
      after incubation with PAT. The assay has a linear response in the 50 ng.mL-1 to
      0.5 pg.mL-1 PAT concentration range and a 0.27 pg.mL-1 lower detection limit. The
      sensor is specific, reproducible, repeatable, and long-term stable. It was
      successfully applied to the determination of PAT in spiked juice samples.
      Graphical abstract Schematic representation of aptamer based detection of patulin
      (PAT). It is based on the fact that ZnO nanorods on the surface of the electrode
      increase the loading of the gold nanoparticles and the aptamers, thereby
      improving the electrode performance.

PMID- 30220002
TI  - Banking brains: a pre-mortem "how to" guide to successful donation.
AB  - A review of the brain banking literature reveals a primary focus either on the
      factors that influence the decision to become a future donor or on the brain
      tissue processing that takes place after the individual has died (i.e., the front
      end or back-end processes). What has not been sufficiently detailed, however, is
      the complex and involved process that takes place after this decision to become a
      future donor is made yet before post-mortem processing occurs (i.e., the large
      middle-ground). This generally represents a period of many years during which the
      brain bank is actively engaged with donors to ensure that valuable clinical
      information is prospectively collected and that their donation is eventually
      completed. For the past 15 years, the Essential Tremor Centralized Brain
      Repository has been actively involved in brain banking, and our experience has
      provided us valuable insights that may be useful for researchers interested in
      establishing their own brain banking efforts. In this piece, we fill a gap in the
      literature by detailing the processes of enrolling participants, creating
      individualized brain donation plans, collecting clinical information and
      regularly following-up with donors to update that information, and efficiently
      coordinating the brain harvest when death finally arrives.

PMID- 30220004
TI  - Body ownership and the absence of touch: approaching the rubber hand inside and
      outside peri-hand space.
AB  - It is widely accepted that the integration of visual and tactile information is a
      necessity to induce ownership over a rubber hand. This idea has recently been
      challenged by Ferri et al. (Proc R Soc B 280:1-7, 2013), as they found that sense
      of ownership was evident by mere expectation of touch. In our study, we aimed to
      further investigate this finding, by studying whether the mere potential for
      touch yields a sense of ownership similar in magnitude to that resulting from
      actually being touched. We conducted two experiments. In the first experiment,
      our set-up was the classical horizontal set-up (similar to Botvinick and Cohen,
      Nature 391:756, 1998). Sixty-three individuals were included and performed the
      classical conditions (synchronous, asynchronous), an approached but not touched
      (potential for touch), and a 'visual only' condition. In the second experiment,
      we controlled for differences between the current set-up and the vertical set-up
      used by Ferri et al. (Proc R Soc B 280:1-7, 2013). Fifteen individuals were
      included and performed a synchronous and various approaching conditions [i.e.,
      vertical approach, horizontal approach, and a control approach (no hands)]. In
      our first experiment, we found that approaching the rubber hand neither induced a
      larger proprioceptive drift nor a stronger subjective sense of ownership than
      asynchronous stimulation did. Generally, our participants gained most sense of
      ownership in the synchronous condition, followed by the visual only condition.
      When using a vertical set-up (second experiment), we confirmed previous
      suggestions that tactile expectation was able to induce embodiment over a foreign
      hand, similar in magnitude to actual touch, but only when the real and rubber
      hand were aligned on the vertical axis, thus along the trajectory of the
      approaching stimulus. These results indicate that our brain uses bottom-up
      sensory information, as well as top-down predictions for building a
      representation of our body.

PMID- 30220005
TI  - Effect of external fixation rod coupling in computed tomography.
AB  - External fixation is a common tool in the treatment of complex fractures,
      correction of limb deformity, and salvage arthrodesis. These devices typically
      incorporate radio-opaque metal rods/struts connected at varying distances and
      orientations between rings. Whilst the predominant imaging modality is plain film
      radiology, computed tomography (CT) may be performed in order for the surgeon to
      make a more confident clinical decision (e.g. timing of frame removal, assessment
      of degree of arthrodesis). We used a fractured sheep leg to systematically assess
      CT imaging performance with a Discovery CT750 HD CT scanner (GE Healthcare) to
      show how rod coupling in both traditional Ilizarov and hexapod frames distorts
      images. We also investigated the role of dual-energy CT (DECT) and metal artefact
      reduction software (MARS) on the visualisation of the fractured leg. Whilst
      mechanical reasons predominantly dictate the rod/strut configurations when
      building a circular frame, rod coupling in CT can be minimised. Firstly, ideally,
      all or all but one rod can be removed during imaging resulting in no rod
      coupling. If this is not possible, strategies for configuring the rods to
      minimise the effect of the rod coupling on the region of interest are
      demonstrated, e.g., in the case of a four-rod construct, switching the two
      anterior rods to a more central single one will achieve this goal without
      particularly jeopardising mechanical strength for a short period. It is also
      shown that the addition of DECT and MARS results in a reduction of artefacts, but
      also affects tissue and bone differentiation.

PMID- 30220007
TI  - Authors' response to the commentary by Bonaventura and Montecucco on:
      'Characterization of circulating leukocytes and correlation of leukocyte subsets
      with metabolic parameters 1 and 5 years after diabetes diagnosis'.

PMID- 30220006
TI  - Treatment and outcomes in pheochromocytomas and paragangliomas: a study of 110
      cases from a single center.
AB  - PURPOSE: Many pheochromocytomas and paragangliomas (PPGLs) are nowadays diagnosed
      as incidentalomas or by screening. This may have changed outcomes. METHODS: We
      reviewed 110 consecutive cases of PPGLs. Two cases with concurrent ectopic ACTH
      syndrome were excluded. RESULTS: Sixty-five percent had presented as
      incidentalomas, 30% as symptomatic PPGLs, and 5% had been screened (previously
      diagnosed MEN2A). Doxazosin was used in 79%, phenoxybenzamine in 18%, intravenous
      phentolamine in 1%, and no alpha-blockade in the rest. Laparoscopic surgery was
      performed in 70%, but 11% were converted to open surgery. Complications of
      surgery were seen in 20%, and length of stay after surgery was 4 days (2-8) with
      no correlation with alpha-blockade dose or time. In the whole cohort glycemic
      disturbances decreased by surgery (47% vs. 9%, P < 0.001). During 9.6 +/- 7.2
      year (median 8[4-13]) follow-up, 7% developed a new PPGL, 5% a PPGL-metastasis
      (KI67 > 2% n = 2; KI67 <= 1% n = 3; tumor size >= 95 mm n = 4), and 13% died
      (metastatic pheochromocytoma n = 2, hypertensive crisis n = 1, heart failure n =
      2, other malignancies n = 5, and unclear n = 4). Surgery improved blood pressure
      and glycemic disturbances in the incidentaloma and the symptomatic PPGL.
      Recurrence was more common in the screening group. The symptomatic PPGL group was
      more likely to die of a PPGL-related cause. Surgery was more challenging in the
      paragangliomas, with less improvement in glycemic control than in the
      pheochromocytoma group. However, blood pressure and long-term outcomes were
      similar. CONCLUSION: The outcomes seemed slightly better than previous studies.
      Long-term prognosis was similar between pheochromocytomas and paragangliomas.

PMID- 30220008
TI  - On the role of the immunoproteasome in transplant rejection.
AB  - The immunoproteasome is expressed in cells of hematopoietic origin and is induced
      during inflammation by IFN-gamma. Targeting the immunoproteasome with selective
      inhibitors has been shown to be therapeutically effective in pre-clinical models
      for autoimmune diseases, colitis-associated cancer formation, and
      transplantation. Immunoproteasome inhibition prevents activation and
      proliferation of lymphocytes, lowers MHC class I cell surface expression, reduces
      the expression of cytokines of activated immune cells, and curtails  T helper 1
      and 17 cell differentiation. This might explain the in vivo efficacy of
      immunoproteasome inhibition in different pre-clinical disease models for
      autoimmunity, cancer, and transplantation. In this review, we summarize the
      effect of immunoproteasome inhibition in different animal models for
      transplantation.

PMID- 30220009
TI  - Identification of cancer-type specific expression patterns for active aldehyde
      dehydrogenase (ALDH) isoforms in ALDEFLUOR assay.
AB  - Aldehyde dehydrogenases (ALDHs) defend intracellular homeostasis by catalyzing
      the conversion of toxic aldehydes into non-toxic carboxylic acids, which is of
      particular importance to the self-renewal of stem cells and cancer stem cells.
      The widely used ALDEFLUOR assay was initially designed to indicate the activity
      of ALDH1A1 in leukemia and has been demonstrated to detect the enzyme activity of
      several other ALDH isoforms in various cancer types in recent years. However, it
      is still elusive which isoforms, among the 19 ALDH isoforms in human genome, are
      the potential contributors in catalyzing ALDEFLUOR assay in different cancers. In
      the current study, we performed a screening via overexpressing each ALDH isoform
      to assess their ability of catalyzing ALDEFLUOR assay. Our results demonstrate
      that nine isoforms are active in ALDEFLUOR assay, whose overexpression
      significantly increases ALDH-positive (ALDH+) population. Further analysis of the
      expression of these active isoforms in various cancers reveals cancer-type
      specific expression patterns, suggesting that different cancer types may exhibit
      ALDEFLUOR activity through expression of specific active ALDH isoforms. This
      study strongly indicates that a detailed elucidation of the functions for each
      active ALDH isoform in CSCs is necessary and important for a profound
      understanding of the underlying mechanisms of ALDH-associated stemness.

PMID- 30220010
TI  - Revision surgery after instrumental fixation in patient with butterfly vertebra:
      a case report.

PMID- 30220011
TI  - Biological predictors shared by dementia and bullous pemphigoid patients point
      out a cross-antigenicity between BP180/BP230 brain and skin isoforms.
AB  - Bullous pemphigoid (BP) following dementia diagnosis has been reported in the
      elderly. Skin and brain tissues express BP180 and BP230 isoforms. Dementia has
      been associated with rs6265 (Val66Met) polymorphism of the brain-derived
      neurotrophic factor (BDNF) gene and low serum BDNF. Here we investigated a
      possible cross-antigenicity between BP180/BP230 brain and skin isoforms. We
      assessed antibodies against BP180/BP230 and BDNF levels by ELISA and BDNF
      Val66Met SNP by PCR in three groups: 50 BP patients, 50 patients with dementia,
      and 50 elderly controls. Heatmap hierarchical clustering and data mining decision
      tree were used to analyze the patients' demographic and laboratorial data as
      predictors of dementia-BP association. Sixteen percent of BP patients with the
      lowest serological BDNF presented dementia-BP clinical association. Anti
      BP180/230 positivity was unexpected observed among dementia patients (10%, 10%)
      and controls (14%, 1%). Indirect immunofluorescence using healthy human skin
      showed a BP pattern in two of 10 samples containing antibodies against
      BP180/BP230 obtained from dementia group but not in the control samples. Neither
      allelic nor genotypic BDNF Val66Met SNP was associated with dementia or with BP
      (associated or not with clinical manifestation of dementia). Heatmap analysis was
      able to differentiate the three studied groups and confirmed the ELISA results.
      The comprehensive data mining analysis revealed that BP patients and dementia
      patients shared biological predictors that justified the dementia-BP association.
      Autoantibodies against the BP180/BP230 brain isoforms produced by dementia
      patients could cross-react with the BP180/BP230 skin isoforms, which could
      justify cases of dementia preceding the BP disease.

PMID- 30220012
TI  - Long-term persistence of anti-rods and rings antibodies in patients with chronic
      hepatitis C after antiviral treatment.
AB  - Anti-rods and rings (anti-RR) antibodies are related to hepatitis C virus (HCV)
      in patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). Only
      RBV induces rods/rings structures in vitro; but in vivo, the antibody appearance
      is related to the combination of these drugs, because data about patients using
      just one of these drugs alone is missing. Some studies suggest disappearance of
      these antibodies over time. The aim of this study was to describe the occurrence
      of anti-RR in patients with chronic hepatitis C treatment-naive or previously PEG
      IFN/RBV-experienced, evaluating the persistence of anti-RR antibodies long after
      PEG-IFN/RBV treatment. From 2016 to 2017, 70 HCV-infected patients were screened
      for anti-RR using indirect immunofluorescence. Demographic and clinical data
      about previous treatments against HCV were assessed. Thirty-four patients (49%)
      had been previously treated with PEG-IFN/RBV and the average time since they had
      received the last antiviral treatment was 85.4 months. Anti-RR seropositivity was
      detected in 16 patients (23%), and all of these had used PEG-IFN/RBV
      (corresponding to 47% of experienced patients). Previous antiviral treatment and
      previous exposure time to RBV were associated with anti-RR positivity. Median
      time elapsed since last treatment was similar between anti-RR-positive and anti
      RR-negative patients. Anti-RR seropositivity was not observed in treatment-naive
      patients, but was detected in almost half of patients previously treated with PEG
      IFN and RBV, even after a long period without exposure to these drugs. This
      antibody was related to extended prior exposure to ribavirin.

PMID- 30220013
TI  - Synthesis and Studies of Fluorescein Based Derivatives for their Optical
      Properties, Urease Inhibition and Molecular Docking.
AB  - Herein, we design and synthesized new fluorescein based derivatives by insitu
      formation of fluorescein ester and further treated with corresponding hydrazide
      and amine to yield respective compounds i.e. FB1, FB2, FB3 and FB4. The spectral
      purity and characterization was done by using IR, NMR and Mass spectroscopies.
      The synthesized derivatives were examined for their photophysical properties by
      using variety of organic solvents and results were discussed in details. The
      structural diversity of synthesized compounds motivate us to evaluate these
      compounds for urease inhibition. The compound FB3 (IC50 = 0.0456 MUM) shows 100
      fold more active against Jack bean urease than standard drug thiourea (IC50 =
      4.7455 MUM). Other synthesized compounds showed potent activity. Free radical
      percentage scavenging assay further supported the capacity of compounds to urease
      inhibition. While, molecular docking simulations helps to examine the molecular
      interactions of active compounds FB1, FB2, FB3 and FB4 within the binding site of
      urease enzyme.

PMID- 30220014
TI  - Monitoring the Instant Creation of a New Fluorescent Signal for Evaluation of DNA
      Conformation Based on Intercalation Complex.
AB  - Here we report the monitoring the instant creation of a new fluorescent signal
      (FS) aroused from a positively charged water-soluble fluorogenic probe, ethidium
      bromide (EtBr) in the presence of a radical initiator, ammonium persulfate (APS)
      and an accelerator, tetraethylmetilendiamine (TEMED) for evaluation of
      deoxyribonucleic acid (DNA) conformation. The results revealed that the occurred
      FS (lambdaex = 430 nm; lambdamax = 525 nm) is a reduced form of EtBr (lambdaex =
      480 nm; lambdamax = 617 nm) and it is completely distinct from hydroethidine
      (lambdaex = 350 nm; lambdamax = 430 nm), which is two-electron reduced form of
      EtBr. It was noticed that EtBr was reduced to a new FS during the polymerization
      of N, N dimethyacrylamide (DMAA) too, at 25  degrees C in the presence of APS and
      TEMED or at 55  degrees C with only APS, and the rate of formation of FS was
      increased upon treatment time. The effect of nanoclays such as Laponite XLG(r)
      and Laponite XLS(r), which provide a protective environment for DNA in nature,
      were also investigated through the reduction process of EtBr in the absence and
      presence of a water soluble monomer DMAA. We demonstrated that DNA conformation
      might be evaluated by monitoring FS effectuated during the reduction of EtBr in
      the presence of nanoclays having positively and negatively charged surfaces.
      Protective property of DNA against the formation of reduced product was
      elucidated by carrying out the polymerization at 55  degrees C. The results
      revealed that the monitoring of formation of FS in the presence of radical
      initiator could lead to elucidate the conformation of DNA upon formation of
      intercalator complex.

PMID- 30220015
TI  - Synthesis and Evaluation of a Schiff-Based Fluorescent Chemosensors for the
      Selective and Sensitive Detection of Cu2+ in Aqueous Media with Fluorescence Off
      On Responses.
AB  - Copper being an essential nutrient; also pose a risk for human health in
      excessive amount. A simple and convenient method for the detection of trace
      amount of copper was employed using an optical probe R1 based on Schiff base. The
      probe was synthesized by Schiff base condensation of benzyl amine and 2-hydroxy-1
      napthaldehyde and characterized by single X-ray diffraction, 1H NMR and FTIR. By
      screening its fluorescence response in a mixture of DMSO and H2O (20:80, v/v) R1
      displayed a pronounced enhancement in fluorescence only upon treatment with
      copper. Other examined metal ions such as alkali, alkaline and transition had no
      influence. Within a wide pH range 5-12 R1 could selectively detect copper by
      interrupting ICT mechanism that results in CHEF. From Job's plot analysis a 2:1
      binding stoichiometry was revealed. The fluorescence response was linear in the
      range 1-10 * 10-9 M with detection limit 30 * 10-9 M. Association constant was
      determined as 1 * 1011 M-2 by Benesi-Hilderbrand plot. As a fast responsive probe
      it possesses good reproducibility and was employed for detection of copper in
      different water samples.

PMID- 30220016
TI  - Selection and Evaluation of Probiotic and Functional Characteristics of
      Autochthonous Lactic Acid Bacteria Isolated from Fermented Wheat Flour Dough
      Babroo.
AB  - The present study aimed to isolate and identify the potential probiotic lactic
      acid bacteria (LAB) from traditionally fermented wheat flour dough known as
      "babroo." A total of 26 lactic isolates were obtained from 50 different samples
      collected from different locations of the Himalayan province (Himachal Pradesh).
      To ascertain non-pathogenic nature, the isolates were screened by hemolytic
      activity leading to 20 non-hemolytic strains which were subjected to tolerance to
      simulated gastrointestinal conditions. Seven different strains were selected
      based on their tolerance to gastrointestinal conditions. All the selected seven
      isolates were found to be susceptible to ampicillin and resistant to gentamicin.
      The phylogenetic analysis revealed three different strains of Lactobacillus
      fermentum, two strains of Lactobacillus plantarum, and two of Pediococcus
      acidilactici. The isolates exhibit different degrees of cell surface
      hydrophobicity (20.0-42.0%), cellular autoaggregation (5.0-41.0%), and adhesion
      to mucin (35.0-78.0%). The different lactic strains also possessed higher
      antioxidant properties (87.6-92.9%) determined in terms of free radical
      scavenging activity, bile salt hydrolase activity, cholesterol lowering activity
      (49.0-75.0%), and exopolysaccharide production. The principal component analysis
      (PCA) on probiotic attributes indicated that L. plantarum K90, L. fermentum K75,
      and L. fermentum K78 can be used as potential probiotic candidates.

PMID- 30220017
TI  - At the Intersection of Neurodiversity and Gender Diversity.

PMID- 30220018
TI  - Corrections to Oien, Cicchetti, and Nordahl-Hansen's (2018) "Gender Dysphoria,
      Sexuality and Autism Spectrum Disorder: A Systematic Map Review".

PMID- 30220019
TI  - "In Medical School, You Get Far More Training on Medical Stuff than Developmental
      Stuff": Perspectives on ASD from Ontario Physicians.
AB  - This study investigated the knowledge and perceived competence of Ontario
      physicians regarding the diagnosis and treatment of ASDs. Previous research
      demonstrates that many physicians would like more education regarding diagnosis
      and treatment of autism spectrum disorders (ASDs). Twenty-seven Ontario
      physicians filled out a questionnaire and participated in a semi-structured
      interview. Findings revealed that despite participants' high perceived knowledge
      regarding diagnosis and treatment of ASDs, they feel uncomfortable in providing
      care for this population. Furthermore, many participants stated diagnosing and
      treating ASDs is not within their scope of practice. Findings have implications
      for increasing physicians' knowledge of diagnosis and treatment of ASDs as well
      as what is required to enhance healthcare for individuals with ASDs and their
      families.

PMID- 30220020
TI  - Views of Teachers on Anxiety Symptoms in Students with Autism Spectrum Disorder.
AB  - People with autism spectrum disorder (ASD) exhibit comorbidity with anxiety. The
      aim of this study was the investigation of the perception of teachers on anxiety
      in school children with ASD. The Scale Teacher Response (SAS-TR) questionnaire
      was completed by 291 special education and 118 general education teachers,
      providing data on students in their classes with ASD and of typical development
      (TD), respectively. According to the total scores on SAS-TR, 46.8% of the
      children with ASD presented levels of anxiety within the clinical spectrum
      compared with 15.3% of the children of TD. Gender and age were not associated
      with the anxiety scores, but in the children with ASD, higher intelligence
      quotient (IQ) was weakly, and better verbal skills more strongly correlated with
      a higher anxiety level. Teachers' awareness of anxiety symptoms in children with
      ASD may contribute to their social inclusion.

PMID- 30220022
TI  - Systems Oncology: Bridging Pancreatic and Castrate Resistant Prostate Cancer.
AB  - Large investments by pharmaceutical companies in the development of new
      antineoplastic drugs have not been resulting in adequate advances of new
      therapies. Despite the introduction of new methods, technologies, translational
      medicine and bioinformatics, the usage of collected knowledge is unsatisfactory.
      In this paper, using examples of pancreatic ductal adenocarcinoma (PaC) and
      castrate-resistant prostate cancer (CRPC), we proposed a concept showing that, in
      order to improve applicability of current knowledge in oncology, the re
      clustering of clinical and scientific data is crucial. Such an approach, based on
      systems oncology, would include bridging of data on biomarkers and pathways
      between different cancer types. Proposed concept would introduce a new matrix,
      which enables combining of already approved therapies between cancer types. Paper
      provides a (a) detailed analysis of similarities in mechanisms of etiology and
      progression between PaC and CRPC, (b) diabetes as common hallmark of both cancer
      types and (c) knowledge gaps and directions of future investigations. Proposed
      horizontal and vertical matrix in cancer profiling has potency to improve current
      antineoplastic therapy efficacy. Systems biology map using Systems Biology
      Graphical Notation Language is used for summarizing complex interactions and
      similarities of mechanisms in biology of PaC and CRPC.

PMID- 30220021
TI  - Expression of microRNA-150 and its Target Gene IGF2BP1 in Human Osteosarcoma and
      their Clinical Implications.
AB  - Previous study revealed that microRNA (miR)-150 might function as a tumor
      suppressor in osteosarcoma partially by targeting Insulin-Like Growth Factor 2
      mRNA-Binding Protein 1 (IGF2BP1). The aim of this study was to investigate the
      clinical significance of miR-150-IGF2BP1 axis in human osteosarcoma which remains
      unclear. At first, expression levels of miR-150, and IGF2BP1 mRNA and protein in
      20 osteosarcoma and matched adjacent noncancerous tissues were respectively
      detected by quantitative real-time PCR and western blot analyses. Then,
      subcellular localization and expression pattern of IGF2BP1 protein in 100
      osteosarcoma tissues were examined by immunohistochemistry. Associations of miR
      150/IGF2BP1 expression with various clinicopathological features and patients'
      prognosis were also statistically evaluated. As a result, miR-150 expression was
      significantly decreased, while IGF2BP1 mRNA and protein expression were
      dramatically increased in osteosarcoma tissues compared to matched adjacent
      noncancerous tissues (all P < 0.001). Immunostaining of IGF2BP1 protein was
      localized in cytoplasm of tumor cells in osteosarcoma tissues. Statistically, low
      miR-150 expression and/or high IGF2BP1 protein immunoreactive score were all
      significantly associated with high tumor grade, presence of metastasis and
      recurrence, as well as poor response to chemotherapy (all P < 0.05). Moreover,
      miR-150, IGF2BP1 and combined miR-150/IGF2BP1 expressions were all identified as
      independent prognostic factors for overall and disease-free survivals of
      osteosarcoma patients (all P < 0.05). In conclusion, our data suggest that miR
      150 and its downstream target IGF2BP1 may be a crucial axis for the development,
      progression and patients' prognosis of ostesarcoma. The newly identified miR
      150/IGF2BP1 axis might be a novel potential therapeutic target for osteosarcoma
      treatment.

PMID- 30220023
TI  - Cystoscopic ureteral stent placement: techniques and tips.
AB  - INTRODUCTION AND HYPOTHESIS: We present a video demonstrating technical
      considerations and tips for cystoscopic placement of external, lighted, and
      internal ureteral stents. METHODS: Cystoscopic ureteral stent placement is useful
      in cases where difficult pelvic periureter dissection is expected or encountered.
      In this video, we review cystoscopy basics, our approach to various types of
      retrograde stent placement, and performing retrograde pyelograms. Traditional
      external ureteral stent and lighted stent placement for prophylactic purposes are
      discussed, with attention to understanding stent markings, appropriate
      resistance, and steps for externalization. Internal, double-J ureteral stent
      placement with the use of fluoroscopy is initiated with placement of a guidewire.
      An open-ended ureteral catheter is advanced over the wire in the pelvic portion
      of the ureter, and a retrograde pyelogram is performed. The wire is reintroduced
      and the stent advanced to the renal pelvis under fluoroscopy. The proximal curl
      is confirmed to be in the appropriate position with fluoroscopy. The string
      attached to the stent is then cut and removed, the guidewire is removed, and the
      stent is deployed with the distal curl in the bladder. CONCLUSIONS: This video
      reviews key steps for cystoscopic ureteral stent placement in a prophylactic
      setting, cases of challenging anatomy, or ureteral injury.

PMID- 30220024
TI  - Therapeutic role of granulocyte colony-stimulating factor (G-CSF) for infertile
      women under in vitro fertilization and embryo transfer (IVF-ET) treatment: a meta
      analysis.
AB  - OBJECTIVE: The aim of this meta-analysis is to explore the beneficial role of
      granulocyte colony-stimulating factor (G-CSF) on infertile women under artificial
      reproduction technology treatment. METHOD: Medline, Embase and ISI Web of Science
      databases were searched to identify relevant randomized control trials. Studies
      before July, 2017 were included for primary screening. Meta-analysis of the total
      and subgroup patients was conducted, and relative risks (RRs) and their 95%
      confidence intervals (95% CI) were calculated by a fixed-effect model if no
      heterogeneity (evaluated as I2 statistic) existed. Otherwise, a random-effects
      model was adopted. Subgroup analysis was performed by administrating route or
      clinical indication. Egger test and influence analysis were conducted to evaluate
      the publication bias and study power, respectively. RESULTS: The final selection
      enrolled 10 RCTs, involving 1016 IVF-ET cycles (521 distributed to the G-CSF
      group and 495 to the control). Compared with control group, G-CSF administration
      could significantly improve clinical pregnancy rate (CPR, RR 1.89, 95% CI 1.53
      2.33), while it had no beneficial effect on embryo implantation rate (IR, RR
      1.84, 95% CI 0.84-4.03). The subgroup analysis by administration route showed
      that both uterine infusion and subcutaneous injection can produce a substantial
      increase in CPR, with the pooled RRs (95% CI) 1.46 (1.04-2.05) and 2.23 (1.68
      2.95), respectively. Nevertheless, most of included RCTs dealt with the RIF
      subjects, and the pooled analysis of this data showed a higher PR and IR in G-CSF
      group as compared to that in the control, with the RRs (95% CI) 2.07 (1.64-2.61)
      and 1.52 (1.08-2.14), respectively. Egger regression test did not demonstrate any
      significance for the publication bias. CONCLUSION: G-CSF administration has a
      beneficial role on the clinical outcome after embryo transfer by both routes of
      local infusion and systematic administration, especially for the cases with RIF.
      Further RCTs are needed to investigate the role of G-CSF in thin endometrium
      patients.

PMID- 30220025
TI  - Afamin: an early predictor of preeclampsia.
AB  - PURPOSE: Oxidative stress is involved in the pathogenesis of hypertensive
      disorders such as preeclampsia (PE) and associated with the human vitamin E
      binding protein afamin. The aim of this study was, therefore, to analyse afamin
      in the first trimester of patients developing PE later in pregnancy and in
      control subjects without pregnancy complications. METHODS: In this retrospective
      study, 137 serum samples from the first trimester of pregnancy were analysed in a
      case-control study design. 39 patients developed PE (10 patients with early-onset
      and 29 patients with late onset disease) and 98 women had an uncomplicated
      pregnancy. Mann-Whitney U test, t test, logistic regression and ROC analyses were
      performed for statistical evaluation. RESULTS: Pregnant women developing PE
      presented with higher afamin concentrations in the first trimester [median 101.81
      mg/L; interquartile range (IQR) 88.94-113.26] compared to subjects with
      uncomplicated pregnancy (median 86.40; IQR 75.26-96.92; p < 0.001). After
      adjusting for confounders, the odds ratio per afamin standard deviation was 1.60
      (95% CI: 1.04-2.58; p = 0.04). An afamin threshold concentration of 87.8 mg/L
      exhibited the best sensitivity (79.5%) and specificity (57.1%) in predicting PE.
      Subgroup analysis of early- and late-onset disease resulted in substantially
      higher afamin concentrations in women with developing late-onset PE compared to
      controls (p < 0.001) with an odds ratio per afamin standard deviation of 1.62
      (95% CI: 0.98-2.70; p = 0.06). CONCLUSIONS: Serum afamin concentrations are
      elevated in the first trimester among patients developing PE compared to
      controls. Substantial differences were observed mainly among patients with late
      onset PE.

PMID- 30220027
TI  - Prognostic value of paravertebral muscle density in patients with spinal
      metastases from gastrointestinal cancer.
AB  - PURPOSE: Morphometric analyses have shown that trunk muscle mass and density are
      associated with mortality in cancer patients. Because of the low incidence of
      spinal metastasis from gastrointestinal cancer and the limited life expectancy of
      these patients, few studies have been reported in this population. We evaluated
      the prognostic value of trunk muscle area and density in predicting overall
      survival. METHODS: The data from 78 patients with spinal metastases from
      gastrointestinal cancer, collected from February 2009 to July 2016, were
      evaluated. Psoas muscle and paravertebral muscle area and density were measured
      at the L3 level on CT scans taken at the time nearest to the diagnosis of spinal
      metastasis. Cox proportional hazards analysis was performed to evaluate the
      factors independently associated with overall survival. RESULTS: The mean patient
      age was 68.3 years (range, 42-88 years). The overall median survival time was 4.8
      months: 2.2 months in the extremely rapid growth group (stomach, biliary tract,
      and pancreas) and 7.6 months in the rapid growth group (esophagus, liver, and
      colorectum). Multivariate analyses showed that lower paravertebral muscle density
      (HR 2.23 [95% CI 1.24-3.99], p = 0.007), extremely rapid growth group, presence
      of abnormal laboratory data, poor performance status, and chemotherapy after
      spinal metastasis were independent prognostic factors. CONCLUSIONS: Median
      overall survival was poor among patients with spinal metastases from
      gastrointestinal carcinoma, especially among those with gastric, biliary tract,
      or pancreatic cancer. Lower paravertebral muscle density was an independent poor
      prognostic factor in patients with spinal metastases from gastrointestinal
      cancer.

PMID- 30220026
TI  - Selection of aptamers against pathogenic bacteria and their diagnostics
      application.
AB  - Aptamers are short nucleotide sequences which can specifically bind to a variety
      of targets with high affinity. They are identified and selected via systematic
      evolution of ligands by exponential enrichment (SELEX). Compared to antibodies,
      aptamers offer several advantages including easy labeling, high stability and
      lower cost. Those advantages make it possible to be a potential for use as a
      recognition probe to replace antibody in the diagnostic field. This article is
      intended to provide a comprehensive review, which is focused on systemizing
      recent advancements concerning SELEX procedures, with special emphasis on the key
      steps in SELEX procedures. The principles of various aptamer-based detections of
      pathogenic bacteria and their application are discussed in detail, including
      colorimetric detection, fluorescence detection, electrochemical detection,
      lateral flow strip test, mass sensitive detection and PCR-based aptasensor. By
      discussing recent research and future trends based on many excellent publications
      and reviews, we attempt to give the readers a comprehensive view in the field of
      aptamer selection against pathogenic bacteria and their diagnostics application.
      Authors hope that this review will promote lively and valuable discussions in
      order to generate new ideas and approaches towards the development of aptamer
      based methods for application in pathogenic bacteria diagnosis.

PMID- 30220028
TI  - Gaps in communication between cancer patients and healthcare providers: symptom
      distress and patients' intentions to disclose.
AB  - PURPOSE: Good communication between patients and healthcare professionals (HCPs)
      is an important contributor to patient well-being. Few studies have focused on
      the gaps in communication between patients and HCPs about symptoms. This study
      examined patients' perspectives on symptom distress, intention to discuss
      symptoms, and actual symptom discussion in medical oncology visits. METHODS: This
      was a cross-sectional descriptive study. Ninety-four patients provided
      demographic and clinical information and completed the Memorial Symptom
      Assessment Scale. Patients also answered questions about their plans for
      communication-and after the visit, their actual communication-with their medical
      team about their symptoms. RESULTS: Patients reported many symptoms by
      questionnaire; however, they did not plan to discuss-nor actually discussed-most
      of their symptoms with their HCPs. For all symptoms, fewer than 42% of patients
      with the symptom intended to discuss it (except for lack of energy and pain) and
      less than 50% actually discussed the symptom. For bothersome symptoms, less than
      42% of those with the symptom intended to discuss it (except for lack of energy)
      and less than 40% actually discussed the symptom. Psychological symptoms were
      endorsed by 24-41% of patients, depending on the symptom; however, of those
      endorsing a symptom, most did not discuss it with an HCP. CONCLUSIONS: Results of
      this study support the perception of communication gaps between patients and HCPs
      about symptoms. Better understanding of these gaps is needed to ensure that
      patient-centered care is delivered and that patients' symptoms can be
      appropriately managed in oncology clinics.

PMID- 30220029
TI  - Predictors of sedentary behavior among colorectal survivors.
AB  - PURPOSE: Colorectal cancer (CRC) survivors spend approximately 9 h per day in
      sedentary behavior (SED), despite recommendations to reduce sitting time. The
      purpose of this study was to examine predictors of SED among CRC survivors over a
      1-year duration. METHODS: Male and female CRC survivors (< 5 years since
      diagnosis) participated in a 12-week moderate-to-vigorous physical activity
      randomized controlled trial. To measure SED, participants were given a CSA
      monitor to wear for three consecutive days (including one weekend day).
      Additionally, fitness (Treadmill walk test), body composition (bioelectrical
      impedance analysis) and questionnaires (Profile of Mood States, Exercise
      Processes of Change and Self-Efficacy for Exercise) were administered. Follow-up
      assessments were completed at a 3-month, 6-month, and 12-month follow-up.
      RESULTS: Forty-six colorectal survivors (average age = 57.3 +/- 9.7 years)
      completed the 12-month study. Using latent class models, four classes of SED
      behavior over time were identified: class 1 (high and sustained SED over time),
      class 2 (low and sustain SED over time), class 3 (increasing SED over time), and
      class 4 (high SED through 6-months, followed be a marked decrease at 12-months).
      Males were more likely to be in class 1, while majority of females were in class
      3. Those CRC survivors with a better mood at baseline were in class 2, while
      those with poor fitness, high body fat, and higher cognitive processes at
      baseline were in class 3. CONCLUSION: Identifying the characteristics of
      survivors who engage in high SED can help healthcare providers to target their
      efforts to reduce SED.

PMID- 30220030
TI  - Editor's Note.

PMID- 30220031
TI  - CRISPR/Cas9-mediated knockout of HIF-1alpha gene in epithelioma papulosum cyprini
      (EPC) cells inhibited apoptosis and viral hemorrhagic septicemia virus (VHSV)
      growth.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a heterodimer of HIF-1alpha and HIF-1beta,
      and its key role in the regulation of cellular responses to hypoxia has been well
      demonstrated. The participation of HIF-1alpha in apoptosis has been reported in
      mammals, however, a little information is available on the role of HIF-1alpha in
      the progression of apoptosis in fish. In this study, to know the role of HIF
      1alpha in the apoptosis of fish cells, we produced HIF-1alpha knockout
      Epithelioma papulosum cyprini (EPC) cells using a CRISPR/Cas9 vector, and a
      single cell clone showing a heterozygous insertion/deletion (indel) mutation (one
      nucleotide insertion and one nucleotide deletion in HIF-1alpha gene) was chosen
      for further experiments. To confirm the knockout of HIF-1alpha, cells were
      transfected with a hypoxia reporting vector containing hypoxic response elements
      (HREs). EPC cells transfected with the reporting plasmids showed significantly
      increased luminescence by exposure to cobalt chloride, a prolyl hydroxylases
      inhibitor. On the other hand, HIF-1alpha knockout EPC cells showed a non
      responsiveness to a cobalt chloride exposure, suggesting that functional HIF
      1alpha protein was not produced in the HIF-1alpha knockout EPC cells. Apoptosis
      progression induced by camptothecin and viral hemorrhagic septicemia virus (VHSV)
      infection was severely inhibited by HIF-1alpha knockout, and the replication of
      VHSV was significantly retarded in HIF-1alpha knockout EPC cells. These results
      suggest that HIF-1alpha in EPC cells acts as a pro-apoptotic factor in the
      progression of apoptosis triggered by a DNA damaging agent and rhabdoviral
      infection.

PMID- 30220032
TI  - Complete sequence of a novel alphaendornavirus from the phytopathogenic fungus
      Arthrocladiella mougeotii.
AB  - A novel double-stranded RNA (dsRNA) virus, which was provisionally named
      Arthrocladiella mougeotii endornavirus (AmEV), was isolated from Arthrocladiella
      mougeotii, the phytopathogenic fungus infecting Lycium chinense in Beijing,
      China. The genome of AmEV is 11,683 nucleotides in length with a 5' and 3' non
      coding region of 16 and 50 nt, respectively, as well as a single 11,617-nt long
      open reading frame potentially encoding a putative protein of 3,871 amino acids
      with conserved Helicase and RNA-dependent RNA polymerase (RdRp) domains.
      Phylogenetic analysis based on the the amino acid sequence of the RdRp showed
      that AmEV is most closely related to Erysiphe cichoracearum endornavirus (EcEV).

PMID- 30220033
TI  - Griffithsin inhibits porcine reproductive and respiratory syndrome virus
      infection in vitro.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that
      severely disrupts swine production. Despite sustained efforts, the disease is
      still endemic, with high mortality and morbidity. New antiviral strategies to
      control PRRSV are needed. Griffithsin, a red algal lectin, has potent antiviral
      effect on several human enveloped viruses, but this effect has not been
      demonstrated on PRRSV. Here, we first tested the in vitro antiviral activity of
      Griffithsin against PRRSV. Griffithsin exerted strong saccharide-dependent
      antiviral activity against PRRSV, probably through interactions with glycans on
      the surface of PRRSV that interfered with virus entry. Furthermore we revealed
      that Griffithsin's action on PRRSV involved blocking viral adsorption, and it had
      no effect on viral penetration. Besides Our findings also suggested that
      Griffithsin may interfere with cell-to-cell spread to prevent virus transmission.
      The remarkable potency profile of Griffithsin supports its potential value as an
      antiviral agent against PRRSV.

PMID- 30220034
TI  - A case of incidental infection of Hepatitis E virus (HEV) genotype 1 in a
      domestic pig.
AB  - Hepatitis E virus (HEV) infection involving zoonotic genotypes is a public health
      problem in high-income and non-endemic developing countries. Herein we report the
      detection of a human genotype 1 (HEV-1) strain infecting a domestic pig, which is
      not considered a natural reservoir of this genotype. Viral load was quantified in
      stool by Real-Time qPCR and sequence analyses were performed. Infectivity of the
      HEV-1 strain was assesed by in vitro isolation in A549 cell line. Results suggest
      that certain epidemiological settings might favour accidental spillover infection
      and thus influence the host range restriction of HEV.

PMID- 30220035
TI  - A metagenomic study of the rumen virome in domestic caprids.
AB  - This project sought to investigate the domestic caprid rumen virome by developing
      a robust viral DNA isolation and enrichment protocol (utilizing membrane
      filtration, ultra-centrifugation, overnight PEG treatment and nuclease treatment)
      and using RSD-PCR and high throughput sequencing (HTS) techniques. 3.53% of the
      reads obtained were analogous to those of viruses denoting Siphoviridae,
      Myoviridae, Podoviridae, Mimiviridae, Microviridae, Poxviridae, Tectiviridae and
      Marseillevirus. Most of the sequenced reads from the rumen were similar to those
      of phages, which are critical in maintaining the rumen microbial populations
      under its carrying capacity. Though identified in the rumen, most of these
      viruses have been reported in other environments as well. Improvements in the
      viral DNA enrichment and isolation protocol are required to obtain data that are
      more representative of the rumen virome. The 102,130 unknown reads (92.31%) for
      the goat and 36,241 unknown reads (93.86%) for the sheep obtained may represent
      novel genomes that need further study.

PMID- 30220036
TI  - Decrease in the expression level of the gene encoding the putative Bombyx mori
      bidensovirus receptor during virus infection.
AB  - Bombyx mori bidensovirus (BmBDV) is a pathogen that replicates only in the midgut
      columnar cells of silkworms, causing fatal disease. Resistance to BmBDV, which
      does not depend on the viral dose, is determined by a single gene, nsd-2
      (resistance gene). Previously, we identified nsd-2 by positional cloning using B.
      mori genome information and found that this gene encodes a putative amino acid
      transporter that may function as a receptor for BmBDV. In this study, to
      understand the relationship between BmBDV and the putative virus receptor, we
      performed expression analysis of +nsd-2 (allele of nsd-2; susceptibility gene)
      after virus infection. Quantitative RT-PCR analysis using total RNA isolated from
      the midgut of an uninfected and a virus-infected silkworm revealed no change in
      the expression levels of +nsd-2 in the uninfected silkworm, whereas the
      expression levels of +nsd-2 drastically decreased in the virus-infected silkworm.
      Moreover, comparison of the expression pattern between the BmBDV-derived
      transcript and +nsd-2 revealed that the expression level of +nsd-2 decreased with
      an increase in the virus-derived transcript. In addition, expression analysis of
      26 genes encoding other transporters in the midgut demonstrated that the
      expression levels of three other genes also decreased similarly to the decrease
      of the expression levels of +nsd-2 after virus infection. Thus, our results
      suggest that some transporters, including +nsd-2, are affected by BmBDV
      infection.

PMID- 30220037
TI  - Novel circular DNA viruses associated with Apiaceae and Poaceae from South Africa
      and New Zealand.
AB  - Advances in molecular techniques used in viral metagenomics coupled with high
      throughput sequencing is rapidly expanding our knowledge of plant-associated
      virus diversity. Applying such approaches, we have identified five novel circular
      replication-associated protein (Rep)-encoding single-stranded (CRESS) DNA viruses
      from Poaceae and Apiaceae plant from South Africa and New Zealand. These viruses
      have a simple genomic organization, including two open reading frames that likely
      encode a Rep and a capsid protein (CP), a conserved nonanucleotide motif on the
      apex of a putative stem loop structure, and conserved rolling-circle replication
      and helicase motifs within their likely Rep: all suggesting that they replicate
      through rolling-circle replication. The Reps and the CPs putatively encoded by
      these five novel viruses share low to moderate degrees of similarity (22.1 -
      44.6%) with other CRESS DNA viruses.

PMID- 30220038
TI  - Continuous Subcutaneous Insulin Infusion Characteristics in Type 1 Diabetes
      Children and Adolescents in Qatar.
AB  - AIM: To describe continuous subcutaneous insulin infusion (CSII) characteristics
      in type 1 diabetes mellitus (T1DM) children and adolescents using a standardized
      protocol in routine clinical settings in Qatar. METHODS: A total of 138 T1DM
      patients (62 males; 76 females; mean age 9.8 +/- 3.4 years) with a mean diabetes
      duration of 2.4 +/- 1.9 years initiated CSII (MiniMed(r) Veo(r)TM and MiniMed(r)
      640 G insulin pumps; Medtronic, Northridge, CA, USA) in 2016 and 2017. CSII
      characteristics and glycated hemoglobin (HbA1c) were evaluated 1 year after
      treatment initiation. RESULTS: At 1 year after treatment initiation, the insulin
      dose had significantly increased (from 0.59 +/- 0.23 to 0.74 +/- 0.26 U/kg body
      weight per 24; P < 0.05), and the HbA1c level had significantly decreased (from
      9.7 +/- 1.3 to 8.1 +/- 0.6%; P < 0.05). More than 92% of patients used the Bolus
      Wizard feature of the insulin pump at the following settings: insulin-to
      carbohydrate ratio 19.2 +/- 9.3 g; insulin sensitivity factor 131 +/- 68 mg/dl;
      target range 91 +/- 9.3-135 +/- 14.2 mg/dl; active insulin time 3.8 +/- 0.8 h.
      CONCLUSION: Our results show that CSII may significantly improve glucose control
      in T1D children and adolescents who use a standardized protocol. A reduction of
      HbA1c by - 1.6% was achieved at 1 year after CSII initiation. These results need
      to be confirmed in a study with a longer duration.

PMID- 30220039
TI  - Reassessing Coronary Artery Bypass Surgery Versus Percutaneous Coronary
      Intervention in Patients with Type 2 Diabetes Mellitus: A Brief Updated
      Analytical Report (2015-2017).
AB  - INTRODUCTION: In this analysis, we aimed to systematically compare percutaneous
      coronary intervention (PCI) versus coronary artery bypass surgery (CABG) in terms
      of adverse outcomes utilizing data from a recent (2015-2017) population of
      patients with type 2 diabetes mellitus (T2DM). METHODS: An electronic search of
      recent studies (2015-2017) was carried out using 'diabetes mellitus,' 'coronary
      artery bypass surgery,' and 'percutaneous coronary intervention' as the main
      search terms. Uncomplicated T2DM patients with stable coronary artery disease
      (CAD), left main CAD, and multi-vessel disease were included. RevMan software
      (version 5.3) was used to calculate odds ratios (OR) and 95% confidence intervals
      (CIs). RESULTS: Among a total of 13,114 T2DM patients, CABG and PCI patients did
      not differ significantly in their rates of mortality (OR 0.90, 95% CI 0.61-1.31;
      P = 0.57) and cardiac death (OR 1.00, 95% CI 0.78-1.30; P = 0.98). However, rates
      of major adverse events, repeat revascularization, and myocardial infarction were
      significantly higher in the PCI group. Stroke rates did not significantly differ
      between the two groups. CONCLUSION: Mortality (1-5 years) did not significantly
      differ between the CABG and PCI patients with T2DM. However, rates of other major
      adverse events were significantly higher in the PCI patients, suggesting that
      CABG is more advantageous than PCI in patients with T2DM.

PMID- 30220040
TI  - A critical appraisal of the quality of low back pain practice guidelines using
      the AGREE II tool and comparison with previous evaluations: a EuroAIM initiative.
AB  - PURPOSE: To assess the methodologic quality of guidelines for the management of
      low back pain (LBP) and compare their recommendations. METHODS: No ethics
      committee approval was needed for this systematic review. In March 2017, a
      systematic search was performed using MEDLINE, EMBASE, National Guideline
      Clearinghouse, and National Institute for Health and Clinical Excellence to find
      practice guidelines of assessment and management of LBP. The evaluation of
      guidelines quality was performed independently by four authors using the AGREE II
      tool, and the results were compared with previous appraisals performed in 2004
      and 2009. RESULTS: Of 114 retrieved guidelines, eight were appraised. All except
      one reached the level of "acceptable" in overall result, with two of them
      reaching the highest scores. Only two guidelines reached a level of "acceptable"
      in every domain; the others had at least one domain with low scores. The
      guidelines had the higher scores (range = 63-94%) on "Scope and purpose" and
      "Clarity of presentation" (47-89%). "Stakeholder Involvement" has the highest
      variability between the guidelines results (40-96%). "Rigor of Development"
      reached an intermediate mean result (34-90%), "Applicability" (42-70%), and
      "Editorial Independence" (38-85%). Only three guidelines had a radiologist among
      authors and reached higher scores compared to guidelines without a radiologist
      among the authors. Compared to previous assessments, low-level guidelines were
      53% in 2004, 36% in 2009, and 13% in 2017. CONCLUSIONS: Considering all
      guidelines, only one had a "low" overall score, while half of them were rated as
      of "high" quality. Future guidelines might take this into account to improve
      clinical applicability.

PMID- 30220041
TI  - Prehospital care of spinal injuries: a historical quest for reasoning and
      evidence.
AB  - PURPOSE: The practice of prehospital immobilization is coming under increasing
      scrutiny. Unravelling the historical sequence of prehospital immobilization might
      shed more light on this matter and help resolve the situation. Main purpose of
      this review is to provide an overview of the development and reasoning behind the
      implementation of prehospital spine immobilization. METHODS: An extensive search
      throughout historical literature and recent evidence based studies was conducted.
      RESULTS: The history of treating spinal injuries dates back to prehistoric times.
      Descriptions of prehospital spinal immobilization are more recent and span two
      distinct periods. First documentation of its use comes from the early 19th
      century, when prehospital trauma care was introduced on the battlefields of the
      Napoleonic wars. The advent of radiology gradually helped to clarify the
      underlying pathology. In recent decades, adoption of advanced trauma life support
      has elevated in-hospital trauma-care to an high standard. Practice of in-hospital
      spine immobilization in case of suspected injury has also been implemented as
      standard-care in prehospital setting. Evidence for and against prehospital
      immobilization is equally divided in recent evidence-based studies. In addition,
      recent studies have shown negative side-effects of immobilisation in penetrating
      injuries. CONCLUSION: Although widely implementation of spinal immobilization to
      prevent spinal cord injury in both penetrating and blunt injury, it cannot be
      explained historically. Furthermore, there is no high-level scientific evidence
      to support or reject immobilisation in blunt injury. Since evidence in favour and
      against prehospital immobilization is equally divided, the present situation
      appears to have reached something of a deadlock. These slides can be retrieved
      under Electronic Supplementary Material.

PMID- 30220043
TI  - Old wine in new bottles?

PMID- 30220042
TI  - Chordoma: a systematic review of the epidemiology and clinical prognostic factors
      predicting progression-free and overall survival.
AB  - BACKGROUND AND AIMS: The aim of this systematic review is to describe the
      epidemiology of chordoma and to provide a clear overview of clinical prognostic
      factors predicting progression-free and overall survival. METHODS: Four databases
      of medical literature were searched. Separate searches were performed for each of
      the two objectives. Reference and citation tracking was performed. Papers were
      processed by two independent reviewers according to a protocol that included risk
      of bias analysis. Disagreement was resolved by discussion. Pooled analyses were
      planned if homogeneity of data would allow. RESULTS: Incidence-incidence rates
      ranged between 0.18 and 0.84 per million persons per year and varied between
      countries and presumably between races. On average patients were diagnosed in
      their late fifties and gender data indicate clear male predominance. Two of the
      largest studies (n = 400 and n = 544) reported different anatomical
      distributions: one reporting the skull base and sacrococcygeal area affected in
      32% and 29% of cases, whereas the other reporting that they were affected in 26%
      and 45% of cases, respectively. PROGNOSTIC FACTORS: Statistically significant
      adverse prognostic factors predicting progression-free and overall survival
      include female sex, older age, bigger tumour size, increasing extent of tumour
      invasion, non-total resection, presence of metastasis, local recurrence, and
      dedifferentiated histological subtype. CONCLUSIONS: Incidence rate and anatomical
      distribution vary between countries and presumably between races. Most chordomas
      arise in the skull base and sacrococcygeal spine, and the tumour shows clear male
      predominance. Multiple adverse prognostic factors predicting progression-free and
      overall survival were identified in subgroups of patients. These slides can be
      retrieved under Electronic Supplementary Material.

PMID- 30220044
TI  - Predictors of surgical site infection after radical cystectomy: should we enhance
      surgical antibiotic prophylaxis?
AB  - PURPOSE: To compare surgical site infections (SSI) rate after radical cystectomy
      (RC) over time and ascertain whether antibiotic prophylaxis should be enhanced.
      METHODS: All medical records of RC patients in a single tertiary uro-oncology
      center between 2007 and 2017 were analyzed. SSI was defined using the criteria of
      the US Centers for Disease Control and Prevention. All bacterial culture results
      and antimicrobial resistance rates were recorded. Lastly, multivariable logistic
      regression analysis was performed to ascertain SSI predictors. RESULTS: RC was
      performed in 405 patients, of which 96 (23.7%) developed SSI. No differences were
      demonstrated in the mean age, gender, NIDDM prevalence, neoadjuvant chemotherapy,
      positive preoperative urine culture, bowel preparation, and surgery time between
      both groups. However, statistically significant higher median BMI, age-adjusted
      Charlson Comorbidity score, usage of ceftriaxone preoperatively, and intensive
      care unit (ICU) hospitalization were noted in SSI patients. Overall, 62/96
      (63.5%) SSI patients had a positive wound culture, with only 16.7% of the
      pathogens being sensitive to their perioperative antibiotics. Lastly, on
      multivariable analysis rising BMI, preoperative ceftriaxone and ICU
      hospitalization were associated with a higher SSI rate. CONCLUSIONS: Preoperative
      BMI reduction, and maximal preoperative medical optimization in an attempt to
      lower ICU admittance rates, should be part of the ideal strategy for lowering SSI
      rates. Additionally, preoperative antibiotics should be enhanced to harbor-wide
      spectrum coverage, based on local resistance rates.

PMID- 30220045
TI  - Treatments of 1242 bulbar urethral strictures: multivariable statistical analysis
      of results.
AB  - PURPOSE: We investigated the success rate of different surgical techniques for
      bulbar stricture repair. METHODS: Retrospective study of patients with bulbar
      urethral strictures treated using different techniques. The primary outcome of
      the study was to evaluate the overall results of treatment (success vs. failure);
      the secondary outcome was to evaluate the outcome according to any surgical
      technique. Cysto-urethrography was performed 1 month following surgery. Patients
      underwent clinical evaluation, uroflowmetry and residual urine measurement every
      6 months for 2 years after surgery and later once on year. When patient showed
      obstructive symptoms, Qmax < 12 ml/s, the urethrography was repeated. Patients
      who underwent further treatment for recurrent stricture were classified as
      failures. A bivariable and multivariable statistical analysis was performed.
      RESULTS: Overall, 1242 patients were included in the study with mean age 40 years
      (range 12-84). Median stricture length was 4 cm (range 1-8). The median follow-up
      was 103 months (range 12-362). Over 1242 patients, 916 (73.8%) were success and
      326 (26.2%) failures. Fourteen different surgical techniques showed a success
      rate ranging from 87.5 to 14.3%. The multivariable analysis showed that stricture
      length was an independent predictor factors for failure: p < 0.0001 CI 1146-1509.
      End-end anastomosis and oral mucosa graft urethroplasty are independent predictor
      factor of success after internal urethrotomy failure. CONCLUSIONS: Our results
      showed that treatment of bulbar urethral stricture is satisfactory on 73.8% of
      patients, but with a wide range of success rate (from 14.3 to 87.5%) using
      different techniques. Oral mucosa is greatly superior to the skin as substitute
      material.

PMID- 30220047
TI  - The first case of genetically confirmed sparganosis (Spirometra erinaceieuropaei)
      in European reptiles.
AB  - Sparganosis is a zoonosis caused by the spargana (larvae) of Spirometra sp.
      (Diphyllobothriidae). Reptiles are particularly important vectors for the
      transmission of this parasite in Asia; however, their role in sparganosis spread
      in European wildlife is unrecognized. We investigated the infection of reptiles
      with Spirometra sp. in NE Poland, where several mammalian hosts have been
      identified recently and in the past. Of the 59 dead reptiles, plerocercoids were
      found in two grass snakes (Natrix natrix) from the Bialowieza Primeval Forest
      (BPF). The Spirometra erinaceieuropaei species was genetically confirmed using
      the evolutionary conserved nuclear 18S rRNA gene, and then compared to GenBank
      deposits. The sequences were identical to previously investigated Spirometra sp.
      found in Eurasian badger and wild boar from BPF. Our finding is the first
      genetically confirmed record of Spirometra sp. in reptiles in Europe. Since
      reptiles are often a component of mammalian diet, they can be a source of
      Spirometra tapeworm infection in European wildlife; however, further studies are
      needed to investigate the prevalence of infection in reptiles and other non
      mammalian hosts.

PMID- 30220046
TI  - Intestinal helminths and protozoan infections in patients with colorectal cancer:
      prevalence and possible association with cancer pathogenesis.
AB  - The purpose of the present study was to determine the prevalence of intestinal
      helminths and protozoa in colorectal cancer (CRC) patients and to evaluate the
      possible association between the prevalence and CRC pathogenesis. A total of 200
      CRC patients and 200 residents of Tashkent, who had no complaints related to the
      gastrointestinal tract, were examined by triple coproscopy using a concentration
      method and estimations of protozoan infection intensity. Of the CRC patients
      tested, 144 were classified as T1-4N0M0 (without metastases) and 56 were
      classified as T1-4N1-2M0-1 (with metastases). Parasitological examination was
      performed during CRC diagnosis before and after surgery and chemotherapy. A
      significantly higher prevalence of Blastocystis sp., Chilomastix mesnili,
      Jodamoeba butschlii, and Endolimax nana was found in CRC patients than in the
      control population (p < 0.0001), amounting to 80, 20, 22.5, and 11.5%,
      respectively. The high prevalence of Blastocystis sp., as well as the patterns of
      infection intensity, was stable at all stages of examination. The ratio of the
      number of CRC patients with and without Blastocystis sp. in the T1-4N0M0 and T1
      4N1-2M0-1 groups amounted to 3.3 and 7.0, respectively. The ratios for C.
      mesnili, E. coli, J. butschlii, and E. nana in both groups were 0.2 and 0.2, 0.07
      and 0.07, 0.3 and 0.16, and 0.18 and 0.01, respectively. The prevalence of
      helminths and Giardia lamblia in CRC patients and the control population was not
      significantly different. Taken together, these data indicate a possible role for
      Blastocystis sp. in CRC pathogenesis. Diagnosis, treatment, and further
      observation of patients with Blastocystis sp. are necessary at all stages of CRC,
      including during diagnosis and before and after surgery and chemotherapy.

PMID- 30220048
TI  - No difference in outcomes and gait analysis between mechanical and kinematic knee
      alignment methods using robotic total knee arthroplasty.
AB  - PURPOSE: The purpose of this study was to compare clinical outcomes and perform
      gait analysis during walking to identify differences in kinematic and kinetic
      parameters between two alignment methods in robotic-assisted total knee
      arthroplasty (TKA). METHODS: Sixty patients were randomly assigned to undergo
      robotic-assisted TKA using either mechanical (30 patients) or kinematic (30
      patients) alignment method. Clinical outcomes including varus and valgus
      laxities, range of motion (ROM), Hospital for Specific Surgery (HSS), Knee
      Society Score (KSS), and Western Ontario and McMaster Universities (WOMAC) scores
      and radiological outcomes were evaluated. Gait analysis of 3D spatiotemporal,
      kinetic, and kinematic parameters during walking was then performed for 10 age
      and gender matched patients of each group to determine differences between the
      two alignment methods. RESULTS: The median follow-up duration of the mechanical
      method group was 8.7 (range 8.1-9.4) years and that of the kinematic method group
      was 8.4 (range 8.0-9.1) years. Clinical outcomes between the two groups showed no
      significant difference in HSS, WOMAC, ROM, KS pain, or function score at the last
      follow-up. No significant difference in varus and valgus laxity assessment,
      mechanical alignment of the lower limb, or perioperative complications was shown
      between the two groups. In gait analysis, no significant difference in kinematic
      or kinetic parameters was found except for varus angle (p < 0.05) and
      mediolateral ground reaction force (p < 0.05). CONCLUSIONS: Results of this study
      show that mechanical and kinematic knee alignment methods provide comparable
      clinical and radiological outcomes after robotic total knee arthroplasty with an
      average follow-up of 8 years. There were no functional difference during walking
      between the two alignment methods either. LEVEL OF EVIDENCE: II.

PMID- 30220049
TI  - Receptor pharmacophore ensemble (REPHARMBLE): a probabilistic pharmacophore
      modeling approach using multiple protein-ligand complexes.
AB  - Ensemble methods are gaining more importance in structure-based approaches as
      single protein-ligand complexes strongly influence the outcomes of virtual
      screening. Structure-based pharmacophore modeling based on a single protein
      ligand complex with complex feature combinations is often limited to certain
      chemical classes. The REPHARMBLE (receptor pharmacophore ensemble) approach
      presented here examines the ability of an ensemble of selected protein-ligand
      complexes to populate pharmacophore space in the ligand binding site, rigorously
      assesses the importance of pharmacophore features using Poisson statistic and
      information theory-based entropy calculations, and generates pharmacophore models
      with high probabilities. In addition, an ensemble scoring function that combines
      all the resultant high-scoring pharmacophore models to score molecules is
      derived. The REPHARMBLE approach was evaluated on ten DUD-E benchmark datasets
      and afforded good screening performance, as measured by receiver operating
      characteristic, enrichment factor and Guner-Henry score. Although one of the high
      scoring models achieved superior statistical results in each dataset, the
      ensemble scoring function balanced the shortcomings of each model and passed with
      close performance measures. This approach offers a reliable way of choosing the
      best-scoring features to build four-feature pharmacophore queries and customize a
      target-biased 'pharmacophore ensemble' scoring function for subsequent virtual
      screening.

PMID- 30220050
TI  - Extracerebral anatomic blind spots in computed tomography (CT) head: a pictorial
      review of non-traumatic findings.
AB  - CT head has been increasingly performed in the Emergency Department for patients
      presented with trauma, acute neurological or psychological symptoms. Most of the
      emergency physicians and radiologists have undergone dedicated training and are
      capable of identifying and interpreting life-threatening cerebral pathologies.
      However, as most attention is directed to the brain, the extracerebral non
      traumatic pathologies on CT head can easily be overlooked, and some of them
      harbour clinically significant pathologies. We categorise the extracerebral
      anatomic landmarks, illustrate and describe the representative pathologies from
      each category. The purpose of this article is to increase awareness and
      familiarity on the non-traumatic extracerebral pathologies, with the aim of
      achieving comprehensive interpretation of CT head.

PMID- 30220051
TI  - Salvage esophagectomy combined with partial aortic wall resection following
      thoracic endovascular aortic repair.
AB  - OBJECTIVE: Definitive chemoradiotherapy is useful for locally advanced esophageal
      cancer. However, salvage esophagectomy is required when residual or recurrent
      tumor is evident after chemoradiotherapy. We performed salvage esophagectomy
      combined with partial aortic wall resection after thoracic endovascular aortic
      repair for aortic invasion, and we evaluated the results. METHODS: Four patients
      underwent esophagectomy combined with aortic wall resection after thoracic
      endovascular aortic repair because the lesion was diagnosed as stage T4b. We
      evaluated short-term outcomes, including duration of thoracic surgery, blood
      loss, duration of intubation, intensive care unit stay, and postoperative
      morbidity, as well as survival after salvage surgery. RESULTS: Lesions were
      resected with no intraoperative procedural adverse events. Mean thoracic
      operation time was 444 min, and mean thoracic blood loss was 506 g. In all
      patients, complete resection of the lesion was possible with no intraoperative
      adverse events. All patients were extubated on postoperative day 0, and all were
      discharged from the intensive care unit on postoperative day 1. One patient
      experienced grade II wound pain (bilateral chest pain), and another patient
      experienced difficult sputum expectoration (grade IIIA). The mean follow-up time
      was 19.8 months, and two patients were alive with no disease recurrence at the
      time of this report. However, the remaining two patients had died secondary to
      lymph node metastasis. CONCLUSIONS: Salvage esophagectomy combined with partial
      aortic wall resection after thoracic endovascular aortic repair provides
      acceptable short-term outcomes. Future studies are needed to evaluate long-term
      survival and patient selection criteria.

PMID- 30220052
TI  - AM fungi facilitate the competitive growth of two invasive plant species,
      Ambrosia artemisiifolia and Bidens pilosa.
AB  - Invasive species often cause enormous economic and ecological damage, and this is
      especially true for invasive plants in the Asteraceae family. Arbuscular
      mycorrhizal fungi (AMF) play an important role in the successful invasion by
      exotic plant species because of their ability to promote growth and influence
      interspecific competition. However, few studies have evaluated the effects of
      invasive Asteraceae species on AMF diversity and how feedback mechanisms during
      competition with native species subsequently affect the accumulation of nutrient
      resources. Two exotic Asteraceae, Ambrosia artemisiifolia and Bidens pilosa, were
      monitored during competition with a native grass species, Setaria viridis, which
      is being replaced by these exotic species in natural areas around the study site.
      From these species continuously maintained in a field plot for 5 years, we
      collected the rhizosphere soil and cloned and identified soil AMF. Furthermore,
      AM fungal spores were isolated from rhizosphere soil of the two invasive species
      and used as inoculum in greenhouse experiments, to compare growth and nutrient
      accumulation during competition. The results indicate that although the AMF
      diversity in the rhizosphere soil of A. artemisiifolia and B. pilosa differed,
      the three most abundant species (Septoglomus viscosum, Septoglomus constrictum,
      Glomus perpusillum) were identical. The addition of AMF inoculum changed the
      competition between the plants, increasing the competitive ability of the
      invasives and decreasing that of the native. The results show a similar AMF
      community composition between A. artemisiifolia and B. pilosa, increased AMF root
      colonization of the invasive species during competition, AMF-enhanced N
      accumulation, and AMF-facilitated competitive growth of the invasive species.

PMID- 30220053
TI  - Evolving Decisions: Perspectives of Active and Athletic Individuals with
      Inherited Heart Disease Who Exercise Against Recommendations.
AB  - Individuals with hypertrophic cardiomyopathy (HCM) and long QT syndrome (LQTS)
      are advised to avoid certain forms of exercise to reduce their risk of sudden
      death. Cardiovascular genetic counselors facilitate both adaptation to, and
      decision-making about, these exercise recommendations. This study describes
      decision-making and experiences of active adults who exercise above physicians'
      recommendations. Purposive sampling was used to select adults with HCM and LQTS
      who self-identified as exercising above recommendations. Semi-structured
      interviews explored participants' decision-making and the psychological impact of
      exercise recommendations. Fifteen individuals were interviewed (HCM: 10; LQTS: 5;
      mean age: 40). Transcripts were coded and analyzed for underlying themes. Despite
      exercising above recommendations, nearly all participants made some modifications
      to their prior exercise regimen. Often these decisions changed over time,
      underscoring the importance of shared decision-making conversations beyond the
      initial evaluation. The importance of exercise was frequently cited as a reason
      for continued exercise, as were perceptions of sudden death risk as low,
      acceptable, or modifiable. Many participants reported that family and friends
      supported their exercise decisions, with a minority having family or friends that
      expressed significant reservations. Genetic counselors, cardiologists, and nurses
      can use these data to inform their counseling regarding exercise recommendations.

PMID- 30220054
TI  - CCN6 regulates IGF2BP2 and HMGA2 signaling in metaplastic carcinomas of the
      breast.
AB  - PURPOSE: Metaplastic breast carcinomas are an aggressive subtype of triple
      negative breast cancer (TNBC) in which part or all of the adenocarcinoma
      transforms into a non-glandular component (e.g., spindled, squamous, or
      heterologous). We discovered that mammary-specific Ccn6/Wisp3 knockout mice
      develop mammary carcinomas with spindle and squamous differentiation that share
      upregulation of the oncofetal proteins IGF2BP2 (IMP2) and HMGA2 with human
      metaplastic carcinomas. Here, we investigated the functional relationship between
      CCN6, IGF2BP2, and HMGA2 proteins in vitro and in vivo, and their expression in
      human tissue samples. METHODS: MMTV-cre;Ccn6fl/fl tumors and spindle TNBC cell
      lines were treated with recombinant CCN6 protein or vehicle. IGF2BP2 was
      downregulated using shRNAs in HME cells with stable CCN6 shRNA knockdown, and
      subjected to invasion and adhesion assays. Thirty-one human metaplastic
      carcinomas were arrayed in a tissue microarray (TMA) and immunostained for CCN6,
      IGF2BP2, and HMGA2. RESULTS: CCN6 regulates IGF2BP2 and HMGA2 protein expression
      in MMTV-cre;Ccn6fl/fl tumors, in MDA-MB-231 and - 468, and in HME cells. CCN6
      recombinant protein reduced IGF2BP2 and HMGA2 protein expression, and decreased
      growth of MMTV-cre;Ccn6fl/fl tumors in vivo. IGF2BP2 shRNA knockdown was
      sufficient to reverse the invasive abilities conferred by CCN6 knockdown in HME
      cells. Analyses of the TCGA Breast Cancer Cohort (n = 1238) showed that IGF2BP2
      and HMGA2 are significantly upregulated in metaplastic carcinoma compared to
      other breast cancer subtypes. In clinical samples, low CCN6 is frequent in tumors
      with high IGF2BP2/HMGA2 with spindle and squamous differentiation. CONCLUSIONS:
      These data shed light into the pathogenesis of metaplastic carcinoma and
      demonstrate a novel CCN6/IGF2BP2/HMGA2 oncogenic pathway with biomarker and
      therapeutic implications.

PMID- 30220055
TI  - Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for
      HER2-positive localized breast cancer.
AB  - PURPOSE: Based on improvement in pathologic complete response (pCR) in the
      NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for
      HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP
      (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and
      TCHP (docetaxel, carboplatin + HP). However, in the United States,
      doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing
      neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with
      localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant
      regimens and AC-TH. METHODS: We reviewed clinicopathological characteristics of
      patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant
      pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a
      large academic medical institution and two affiliated community sites. pCR was
      defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis
      were used for statistical analysis. RESULTS: In this study (N = 121), pCR was
      numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP
      (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly
      less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP
      also resulted in the least dose reductions, lowest rate of hospitalization, and
      lowest rate of treatment discontinuation. CONCLUSIONS: Pertuzumab-based regimens,
      including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP
      regimen associated with the best tolerability among patients with localized HER2+
      breast cancer. Given the various neoadjuvant regimens, additional studies are
      needed to determine optimal treatment sequencing and escalation/de-escalation
      strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.

PMID- 30220056
TI  - Predication of post-operative outcome of colectomy in ulcerative colitis patients
      using Model of End-Stage Liver Disease Score.
AB  - PURPOSE: Model of End-Stage Liver Disease (MELD) score was developed to predict
      mortality in patients with liver disease. The aim of this study was to
      investigate the relationship between preoperative MELD score and 30-day surgical
      outcomes using the American College of Surgeons National Surgical Quality
      Improvement Program. METHODS: Patients with ulcerative colitis (UC) (ICD: 556.X)
      who underwent colectomy were identified from NSQIP 2005 to 2013. The primary
      outcomes were bleeding complications, and overall morbidity and mortality.
      RESULTS: A total of 7534 UC patients undergoing colectomy were identified.
      Patients with a higher MELD score had a longer hospital stay; more bleeding; and
      cardiac, respiratory, renal, thromboembolic, and septic complications as well as
      mortality. Patients were stratified into 4 groups by MELD score: < 7, 7-11, 12
      15, and > 15 and a stratified multivariate analysis was done. Patients with a
      MELD score 12-15 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-1.3) and
      MELD > 15 (OR 2.6, 95%CI 1.5-4.7) were at significant risk for bleeding
      complication. Apart from the MELD score, the presence of ascites (OR 2.5, 95%CI
      1.2-5.1) or varices (OR 1.0, 95%CI 1.01-1.03) was also significantly associated
      with post-operative bleeding complication. MELD 12-15 and MELD > 15 were also
      found to be risk factors for overall morbidity (OR 5.3, 95%CI 1.8-15.7; OR 10.3,
      95%CI 3.6-29.7, respectively) and mortality (OR 3.3, 95%CI 1.3-8.4; OR 5.9, 95%CI
      2.4-14.6, respectively). CONCLUSION: UC patients with a higher MELD score were
      associated with a higher post-colectomy morbidity and mortality. MELD score > 11
      was an independent indicator for post-operative bleeding, and overall
      complications and mortality.

PMID- 30220057
TI  - Using multiplex networks to capture the multidimensional nature of social
      structure.
AB  - Network analysis has increasingly expanded our understanding of social structure
      in primates and other animal species. However, most studies use networks
      representing only one interaction type, when social relationships (and the
      emerging social structure) are the result of many types of interactions and their
      interplay through time. The recent development of tools facilitating the
      integrated analysis of multiple interaction types using multiplex networks has
      opened the possibility of extending the insight provided by social network
      analysis. We use a multiplex representation of interactions among the members of
      a group of wild Geoffroy's spider monkeys (Ateles geoffroyi), to study their
      social structure. We constructed a six-layered multiplex network based on three
      indices of overt social interactions (aggression, embraces, grooming) and three
      distance-based indices (contact, proximity, and association). With tools provided
      by the MuxViz software, we assessed the relevance of including all six indices in
      our analysis, the role of individuals in the network (through node versatility),
      and the presence of modules and non-random triadic structures or motifs. The
      multiplex provided information which was not equivalent to any individual layer
      or to the simple aggregation of layers. Network patterns based on associations
      did not correspond with those observed for overt-interactions or for the
      multiplex structure. Males were the most versatile individuals, while multiplex
      modularity and motifs highlighted the relevance of different interaction types
      for the overall connectivity of the network. We conclude that the multiplex
      approach improves on previous methods by retaining valuable information from each
      interaction type and how it is patterned among individuals.

PMID- 30220058
TI  - Choline Rescues Behavioural Deficits in a Mouse Model of Rett Syndrome by
      Modulating Neuronal Plasticity.
AB  - Rett syndrome (RTT) is a postnatal neurodevelopmental disorder that primarily
      affects girls, with 95% of RTT cases resulting from mutations in the methyl-CpG
      binding protein 2 (MECP2) gene. Choline, a dietary micronutrient found in most
      foods, has been shown to be important for brain development and function.
      However, the exact effects and mechanisms are still unknown. We found that 13
      mg/day (1.7 * required daily intake) of postnatal choline treatment to Mecp2
      conditional knockout mice rescued not only deficits in motor coordination, but
      also their anxiety-like behaviour and reduced social preference. Cortical neurons
      in the brains of Mecp2-conditional knockout mice supplemented with choline showed
      enhanced neuronal morphology and increased density of dendritic spines. Modelling
      RTT in vitro by knocking down the expression of the MeCP2 protein with shRNA, we
      found that choline supplementation to MeCP2-knockdown neurons increased their
      soma sizes and the complexity of their dendritic arbors. Rescue of the
      morphological defects could lead to enhanced neurotransmission, as suggested by
      an observed trend of increased expression of synaptic proteins and restored
      miniature excitatory postsynaptic current frequency in choline-supplemented MeCP2
      knockdown neurons. Through the use of specific inhibitors targeting each of the
      known physiological pathways of choline, synthesis of phosphatidylcholine from
      choline was found to be essential in bringing about the changes seen in the
      choline-supplemented MeCP2-knockdown neurons. Taken together, these data reveal a
      role of choline in modulating neuronal plasticity, possibly leading to
      behavioural changes, and hence, a potential for using choline to treat RTT.

PMID- 30220059
TI  - Persistent Overexposure to N-Methyl-D-Aspartate (NMDA) Calcium-Dependently
      Downregulates Glutamine Synthetase, Aquaporin 4, and Kir4.1 Channel in Mouse
      Cortical Astrocytes.
AB  - Astrocytes express N-methyl-D-aspartate (NMDA) receptor (NMDAR) but its functions
      in these cells are not well defined. This study shows that the sustained exposure
      (8-72 h) of mouse astrocytes to NMDA decreases the expression of the functional
      astroglia-specific proteins, glutamine synthetase (GS), and the water channel
      protein aquaporin-4 (AQP4) and also reduces GS activity. Similar to rat
      astrocytes (Obara-Michlewska et al. Neurochem Int 88:20-25, 2015), the exposure
      of mouse astrocytes to NMDA also decreased the expression of the inward
      rectifying potassium channel Kir4.1. NMDA failed to elicit the effects in those
      cells incubated in the absence of Ca2+ and in those in which the GluN1 subunit of
      the NMDAR was silenced with GluN1 siRNA. The downregulation of GS, AQP4, and
      Kir4.1 observed in vitro may reflect NMDAR-mediated alterations of astrocytic
      functions noted in central nervous system pathologies associated with increased
      glutamate (Glu) release and excitotoxic tissue damage.

PMID- 30220060
TI  - Administering a Telemedicine Program.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the process of
      administering a telemedicine program including reviewing telemedicine guidelines;
      discussing licensing, credentialing, and privileging of providers; outlining
      scheduling and recruitment of patients; and measuring outcomes of a telemedicine
      program. RECENT FINDINGS: Recent literature findings suggest that telemedicine in
      specialty clinics continues to grow at a rapid pace. Medical specialty programs
      should prepare to adopt a practice that includes telemedicine to better serve
      their patients and families who have expressed significant satisfaction with the
      delivery of healthcare in this manner. With the appropriate support, any
      specialty clinic can provide their patients with a telemedicine option which has
      shown to be highly successful for Children's Mercy Allergy, Asthma, & Immunology
      Department.

PMID- 30220061
TI  - Sonocatalytic removal of methylene blue from water solution by cobalt
      ferrite/mesoporous graphitic carbon nitride (CoFe2O4/mpg-C3N4) nanocomposites:
      response surface methodology approach.
AB  - In this study, cobalt ferrite/mesoporous graphitic carbon nitride (CoFe2O4/mpg
      C3N4) nanocomposites were successfully synthesized by using a two-step protocol.
      Firstly, monodispersed CoFe2O4 nanoparticles (NPs) were synthesized via thermal
      decomposition of metal precursors in a hot surfactant solution and then they were
      assembled on mpg-C3N4 via a liquid phase self-assembly method. The sonocatalytic
      performance of as-synthesized CoFe2O4/mpg-C3N4 nanocomposites was evaluated on
      the methylene blue (MB) removal from water under ultrasonic irradiation. For this
      purpose, response surface methodology (RSM) based on central composite design
      (CCD) model was successfully utilized to optimize the MB removal over CoFe2O4/mpg
      C3N4 nanocomposites. Analysis of variance (ANOVA) was applied to investigate the
      significance of the model. The results predicted by the model were obtained to be
      in reasonable agreement with the experimental data (R2 = 0.969, adjusted R2 =
      0.942). Pareto analysis demonstrated that pH of the solution was the most
      effective parameter on the sonocatalytic removal of MB by CoFe2O4/mpg-C3N4
      nanocomposites. The optimum catalyst dose, initial dye concentration, pH, and
      sonication time were set as 0.25 g L-1, 8 mg L-1, 8, and 45 min, respectively.
      The high removal efficiency of MB dye (92.81%) was obtained under optimal
      conditions. The trapping experiments were done by using edetate disodium, tert
      butyl alcohol, and benzoquinone. Among the reactive radicals, *OH played a more
      important role than h+ and [Formula: see text] in the MB dye removal process.
      Moreover, a proposed mechanism was also presented for the removal of MB in the
      presence of CoFe2O4/mpg-C3N4 nanocomposites under the optimized sonocatalytic
      conditions. Finally, a reusability test of the nanocomposites revealed a just
      9.6% decrease in their removal efficiency after five consecutive runs.

PMID- 30220062
TI  - Adsorption of heavy metal tolerance strains to Pb2+ and Cd2+ in wastewater.
AB  - The functional strains with high tolerance to heavy metal Pb2+ and Cd2+ were
      screened from soil obtained in a heavy metal waste accumulation area. The
      immobilized biological adsorbent was made by embedding method and used for
      treatment of wastewater containing heavy metals. The effects of initial
      concentration of heavy metals, adsorption time, pH value of wastewater, and
      dosage of adsorbent on adsorption performance were investigated. The study showed
      (1) the strains tested were Brevibacterium and their maximum tolerable
      concentrations for Pb2+ and Cd2+ were 2200 and 700 mg/L, respectively; (2) the
      maximum adsorption rate for Pb2+ and Cd2+ was 87.77% and 57.50% respectively when
      the dosage of adsorbent was 10 g/L and the pH value of wastewater was 6; (3) Pb2+
      and Cd2+ could be adsorbed in the equilibrium solution for 40 min and the maximum
      adsorption capacity reached 114.36 mg/g and 82.12 mg/g, respectively; and (4)
      when the initial pH value of the wastewater was 5-7, the adsorption rate
      decreased with the increase of the concentration, and the initial concentration
      of Pb2+ had a greater effect on the adsorption rate than Cd2+. Langmuir and
      Freundlich equation showed that the adsorption of Pb2+ and Cd2+ was mainly on the
      surface of monolayer. And the pseudo-second-order kinetic equation indicates that
      Cd2+ has a relatively greater adsorption rate than Pb2+ does.

PMID- 30220063
TI  - Pesticide residue profiles in bee bread and pollen samples and the survival of
      honeybee colonies-a case study from Luxembourg.
AB  - Pesticide residues (112 compounds) were quantified by GC-MS/MS or LC-MS/MS in 85
      bee bread samples and 154 pollen samples obtained from five apiaries each with
      three or four colonies (genotype Buckfast) in Luxembourg over the period 2011
      2013. Thiacloprid, chlorfenvinphos, tebuconazole, and methiocarb were found most
      frequently in bee bread while thiacloprid, permethrin-cis, and permethrin-trans
      were detected most frequently in the pollen samples. Three neonicotinoid
      insecticides (clothianidin, imidacloprid, and thiamethoxam) that were restricted
      by an EU regulation in 2013 after our sampling campaign was finished were each
      found in less than 8% of the pollen or bee bread samples. The maximum
      concentrations of thiacloprid, metazachlor, and methiocarb measured in the pollen
      collected by a group of honeybee colonies (n = 5) without survivors within the 3
      year period of observation were 86.20 +/- 10.74 ng/g, 2.80 +/- 1.26 ng/g, and
      below the limit of quantification, respectively. The maximum concentrations of
      the same compounds measured in the pollen collected by a group of honeybee
      colonies with significantly (P = 0.02) more survivors (7 out of 9) than expected,
      if the survivors had been distributed randomly among the groups of colonies, were
      11.98 +/- 2.28 ng/g, 0.44 +/- 0.29 ng/g, and 8.49 +/- 4.13 ng/g, respectively. No
      honeybee colony that gathered pollen containing more than 23 ng/g thiacloprid
      survived the 3-year project period. There was no statistically significant
      association between pesticide residues in the bee bread and the survival of the
      colonies. Actions already taken or planned and potential further actions to
      protect bees from exposure to pesticides are discussed.

PMID- 30220064
TI  - Discovery and mechanism study of a novel chromium-accumulating plant, Lonicera
      japonica Thunb.
AB  - Finding chromium-accumulating plants is of great interest for phytoremediation of
      soil contaminated by chromium (Cr). Inspired by Traditional Chinese Medicine, we
      examined the Cr-resistance and Cr-accumulation of Lonicera japonica Thunb. After
      a two-phase study using both soil and water culture, we found that L. japonica
      could be a novel Cr-accumulating plant, which contains an average Cr(III) content
      of 1297.14 mg.kg-1 in its leaves. The Cr enrichment factor and the Cr transport
      coefficient of Lonicera japonica was 5.19 and 1.79, respectively. Lonicera
      japonica is the fifth Cr-accumulating plant discovered worldwide, and the first
      Cr-accumulating woody plant ever discovered. The results support the conclusions
      drawn from studies of Cr-accumulating Leersia hexandra that oxalic acid
      production can increase Cr tolerance whereas citric acid or malic acid has no
      effect, suggesting that oxalic acid might be a common reason for Cr tolerance in
      all Cr-accumulating plants. Moreover, this study revealed that the production of
      anthocyanin and carotene can also increase Cr(III) tolerance, suggesting that
      anthocyanin and carotene might also account for Cr tolerance in Cr-accumulating
      plants. We believe that the discovery of Lonicera japonica as a Cr-accumulating
      plant will offer great opportunities in phytoremediation, and the success should
      be a strong sign that Traditional Chinese Medicine harbors more secrets to be
      uncovered with modern science.

PMID- 30220066
TI  - Behavioral response and dynamics of Eisenia fetida hemocytes exposed to
      environmentally relevant concentration of sulfentrazone.
AB  - Although the toxicity of the pesticide sulfentrazone in some aquatic organisms is
      known, its effects on edaphic organisms such as earthworms remain completely
      unknown. Thus, we aimed at evaluating the behavior and immune response of Eisenia
      fetida exposed to sulfentrazone at environmentally relevant concentrations (EC).
      E. fetida representatives exposed to this contaminant (for 48 h) were divided in
      the following groups: environmental concentration (EC1x: 318 ng sulfentrazone/g
      of dry weight soil) and EC100x (concentration 100 times higher than in EC1x).
      Based on the avoidance test results, earthworms responded to this pesticide and
      proved the toxicity of sulfentrazone. The observed immune response induction was
      expressed by increased granulocytes presenting phagocytic vacuoles and
      agglomerations/encapsulations, mainly in animals belonging to groups EC1x and
      EC100x. However, the reduced frequency of plasmocytes in these animals'
      hemolymphs suggested that the phagocytic immune response was not efficient to
      assure 100% survival. Our study is the first to report sulfentrazone toxicity in
      an edaphic organism, at environmental concentration.

PMID- 30220065
TI  - Aerobic and oxygen-limited enrichment of BTEX-degrading biofilm bacteria:
      dominance of Malikia versus Acidovorax species.
AB  - Due to their high resistance against environmental challenges, bacterial biofilms
      are ubiquitous and are frequently associated with undesired phenomena in
      environmental industry (e. g. biofouling). However, because of the high
      phylogenetic and functional diversity, bacterial biofilms are important sources
      of biotechnologically relevant microorganisms, e.g. those showing bioremediation
      potential. In our previous work, the high phylogenetic and metabolic diversity of
      a clogging biofilm, developed in a simple aromatic hydrocarbon (BTEX)
      contaminated groundwater well was uncovered. The determination of relationships
      between different groups of biofilm bacteria and certain metabolic traits has
      been omitted so far. Therefore, by setting up new biofilm-based enrichment
      microcosms, the research goal of the present study was to identify the
      aerobic/hypoxic BTEX-degrading and/or prolific biofilm-forming bacteria. The
      initial bacterial community composition as well as temporal dynamics due to the
      selective enrichment has been determined. The obtained results indicated that the
      concentration of dissolved oxygen may be a strong selective force on the
      evolution and final structure of microbial communities, developed in hydrocarbon
      contaminated environments. Accordingly, members of the genus Malikia proved to be
      the most dominant community members of the aerobic BTEX-degrading enrichments.
      Acidovorax spp. dominated the oxygen-limited/hypoxic setup. During the study, a
      strain collection of 23 different bacterial species was obtained. Non-pathogenic
      members of this strain collection, with outstanding biodegradation (e.g.
      Pseudomonas, Variovorax isolates) and biofilm-forming potential (e.g. Rhizobium),
      may potentially be applied in the development of biofilm-based semipermeable
      reactive biobarriers.

PMID- 30220068
TI  - Allergy to Surgical Implants.
AB  - Surgical implants are essential elements of repair procedures to correct worn out
      joints, damaged spinal components, heart and vascular disease, and chronic pain.
      However, many of the materials that provide stability, flexibility, and
      durability to the implants are also immunogenic. Fortunately, allergic responses
      to surgical implants are infrequent. When they do occur, however, the associated
      pain, swelling, inflammation, and decreased range of motion can significantly
      impair the implant function. Given the high numbers of joint replacements
      performed in the developed world, allergic reactions to orthopedic implants form
      the largest category of allergic responses. The most important allergens in this
      category include nickel, cobalt, chromium, and bone cement. These allergens are
      also the most important in reactions to spinal surgeries. Multiple cardiac and
      neurostimulatory devices are constructed of metals and adhesives that can be
      sensitizing in some individuals. Implantable pulse generators, important in
      cardiac pacemakers, gastric stimulators, and neurostimulators, may include
      components made of stainless steel, titanium alloy, platinum and iridium, epoxy
      resins, poly methyl methacrylates, and isocyanates, all of which are immunogenic
      in some patients. Cardiac stents and patches are often made of Nitinol, a
      composite of nickel and titanium. More surgical procedures are closed using skin
      glues, which are also capable of triggering a blistering contact dermatitis.
      Patch testing is the gold standard to determine sensitization, and this review
      provides a list of standard allergens to test for different implants. The
      patients most appropriate for testing include (1) pre-operative joint replacement
      patients with a prior history of skin reactions to metal jewelry, jean snaps,
      watch bands, metal glass frames, artificial nails, or skin glue; (2) post
      operative joint replacement failure patients needing revision without an obvious
      cause such as infection or mechanical incompatibility; and (3) post-operative
      cardiac or neurological patients with localized rash, pain, swelling, or
      inflammation near or over the implant.

PMID- 30220069
TI  - Bionic 3D spheroids biosensor chips for high-throughput and dynamic drug
      screening.
AB  - To perform the drug screening, planar cultured cell models are commonly applied
      to test efficacy and toxicity of drugs. However, planar cultured cells are
      different from the human 3D organs or tissues in vivo. To simulate the human 3D
      organs or tissues, 3D spheroids are developed by culturing a small aggregate of
      cells which reside around the extracellular matrix and interact with other cells
      in liquid media. Here we apply lung carcinoma cell lines to engineer the 3D lung
      cancer spheroid-based biosensor using the interdigitated electrodes for drug
      efficacy evaluation. The results show 3D spheroid had higher drug resistance than
      the planar cell model. The anticarcinogen inhibition on different 3D lung cancer
      spheroid models (A549, H1299, H460) can be quantitatively evaluated by electric
      impedance sensing. Besides, we delivered combination of anticarcinogens
      treatments to A549 spheroids which is commonly used in clinic treatment, and
      found the synergistic effect of cisplatin plus etoposide had higher drug
      response. To simultaneously test the drug efficacy and side effects on multi
      organ model with circulatory system, a connected multiwell interdigitated
      electrode arraywas applied to culture different organoid spheroids. Overall, the
      organization of 3D cancer spheroids-based biosensor, which has higher predictive
      value for drug discovery and personalized medicine screening, is expected to be
      well applied in the area of pharmacy and clinical medicine.

PMID- 30220070
TI  - Effect of Supplementation of Nano Zinc Oxide on Nutrient Retention, Organ and
      Serum Minerals Profile, and Hepatic Metallothionein Gene Expression in Wister
      Albino Rats.
AB  - A study was conducted to validate the effects of nano form of zinc (NZn) on
      nutrient digestibility, zinc retention, organ and serum zinc profile, and hepatic
      metallothionein gene expression in Wistar albino rats (WAR). Nano zinc (NZn) was
      synthesized through chemical method, by using 0.45 M zinc nitrate [Zn(NO3)2.6H2O]
      and 0.9 M sodium hydroxide (NaOH). The NZn particle in its oxide form was
      characterized by TEM-EDAX and XRD, and found to be in nano range (below 100 nm.
      Zinc was supplemented to the Wistar albino rats (WAR) through synthetic semi
      purified diet either without Zn, or as inorganic zinc (IZn; 25 mg/kg), or as
      synthesized NZn (25, 12.5, 6.25, 3.125 or 50 mg/kg DM) for 60 days. The zinc
      content was observed to be significantly (P < 0.05) higher in liver, bone,
      kidney, and serum due to NZn supplementation where NZn-50 had highest zinc
      content and control had the least, without affecting Fe, Mn, and Cu. NZn at 12.5
      mg/kg group rats were either comparable or better than IZn at 25 mg/kg in terms
      of zinc retention, CP digestibility, zinc level in serum, liver, bone, and kidney
      suggesting its better bioavailability simultaneously also reduced fecal excretion
      of zinc to the environment. Metallothionein mRNA expression was upregulated in
      NZn at 25 mg/kg and NZn at 50 mg/kg than IZn at 50 mg/kg. Thus, in WAR, NZn at
      half of the ICAR recommendation (25 mg/kg DM) is as effective as inorganic zinc
      at 100% of recommended dose.

PMID- 30220067
TI  - The impact of propranolol, 17alpha-ethinylestradiol, and gemfibrozil on early
      life stages of marine organisms: effects and risk assessment.
AB  - Pharmaceuticals are ubiquitously detected in the marine environment at the ng
      MUg/L range. Given their biological activity, these compounds are known to induce
      detrimental effects on biota at relatively low exposure levels; however, whether
      they affect early life stages of marine species is still unclear. In this study,
      a set of bioassays was performed to assess the effects of propranolol (PROP), 17
      alpha ethinylestradiol (EE2), and gemfibrozil (GEM) on gamete fertilization and
      embryonic development of mussels (Mytilus galloprovincialis) and sea urchins
      (Paracentrotus lividus), and on the survival of seabream (Sparus aurata) larvae.
      Treatments of PROP (500, 5000, 50,000 ng/L), EE2 (5, 50, 500 ng/L), and GEM (50,
      500, 5000 ng/L) were selected to encompass levels comparable or superior to
      environmental concentrations. Obtained data were tested for dose-response curve
      fitting and the lowest EC10/LC10 used to calculate risk quotients (RQs) based on
      the MEC/PNEC. No alteration was induced by PROP on the mussel gamete
      fertilization, while inhibitory effects were observed at environmental levels of
      EE2 (500 ng/L) and GEM (5000 ng/L). Fertilization was significantly reduced in
      sea urchin at all PROP and EE2 dosages. The 48-h exposure to all pharmaceuticals
      induced the onset of morphological abnormalities in either mussel or sea urchin
      embryos. Alterations were generally observed at environmentally relevant dosages,
      except for PROP in mussels, in which alterations occurred only at 50,000 ng/L. A
      decreased survival of seabream larvae was recorded after 96-h exposure to PROP
      (all treatments), EE2 (50-500 ng/L), and GEM (500 ng/L). A median RQ > 1 was
      obtained for all pharmaceuticals, assigning a high risk to their occurrence in
      marine environments. Overall, results showed that current levels of contamination
      by pharmaceuticals can impact early stages of marine species, which represent
      critical junctures in the resilience of coastal ecosystems.

PMID- 30220071
TI  - Factors Affecting Differential Methylation of DNA Promoters in Arsenic-Exposed
      Populations.
AB  - The exposure/biotransformation of inorganic arsenic (iAs) may perturb DNA
      methylation patterns and subsequently influence disease risk by altering the
      expression of key genes. Interindividual variation in patterns of DNA methylation
      can be explained by the influence of environmental, genetic, and stochastic
      factors. Here, we examined promoter DNA methylation levels with urinary arsenical
      concentrations and investigated the genetic and nongenetic determinants of DNA
      methylation in 105 samples collected from populations in Shanxi Province, China,
      with high levels of arsenic in drinking water. Arsenic concentrations in water
      were determined by atomic absorption spectrophotometry (AA-6800, Shimadzu Co.,
      Kyoto, Japan). Urine samples were measured using an atomic absorption
      spectrophotometer with an arsenic speciation pretreatment system (ASA-2sp,
      Shimadzu Co. Kyoto, Japan) for detection. Gene-specific (CDH1, EREG, ERCC2,
      GSTP1, and MGMT) DNA methylation was quantified by targeted bisulfite sequencing.
      Single-nucleotide polymorphism (SNP) genotyping was performed using a custom-by
      design 2 * 48-Plex SNPscanTM Kit. These results revealed CDH1 with promoter DNA
      methylation levels associated with iAs. After the exclusion of confounding
      factors, age was correlated with increased methylation of the CDH1 gene. The
      susceptibility of the CDH1 and GSTP1 gene promoters to methylation was increased
      in individuals carrying the DNMT3B (SNP rs2424932) GA genotype, and the
      susceptibility of the CDH1 gene promoters to methylation was increased in
      individuals carrying the DNMT3B (SNP rs6087990) TC genotype. Although the above
      results must still be replicated in larger samples, the findings improve our
      understanding of the pathogenesis of arsenic and may highlight certain DNA
      methylation markers as attractive surrogate markers for prevention research.

PMID- 30220072
TI  - Pharmacokinetic determinants of cisplatin-induced subclinical kidney injury in
      oncology patients.
AB  - PURPOSE: The ability to predict and detect clinical and subclinical
      nephrotoxicity early in the course of therapy has the potential to improve long
      term outcomes in cancer patients receiving cisplatin chemotherapy.
      Pharmacokinetic parameters could serve as predictors of cisplatin-induced
      nephrotoxicity. METHODS: Participants [n = 13] were treated with a 1-h cisplatin
      infusion [30-75 mg/m2]. Blood was collected pre-dose and up to 6 h post-dose.
      Urinary biomarkers [KIM-1, calbindin, clusterin, GST-pi, beta2M, albumin, NGAL,
      osteopontin, clusterin, MCP-1, cystatin C, and TFF3] were measured at baseline,
      days 3 and 10. Total and unbound platinum concentrations were measured using
      ICP/MS. Noncompartmental analysis was performed, and correlation and regression
      analyses evaluated the relationships between platinum pharmacokinetics and
      nephrotoxicity. RESULTS: Peak platinum urinary concentrations correlated with
      urinary levels of KIM-1, calbindin, clusterin, GST-pi, beta2M, albumin, NGAL,
      osteopontin, clusterin, cystatin C, and TFF3 at day 10. Unbound platinum plasma
      concentrations at 2 h also correlated with urinary clusterin, beta2M, cystatin C,
      NGAL, osteopontin, and TFF3 at day 3. Regression analyses suggested 2-h total
      plasma platinum concentrations greater than 2000 ng/ml, and peak urinary platinum
      concentrations above 24,000 ng/ml may serve as potential approximations for
      elevated risk of nephrotoxicity. Platinum area under the plasma concentration
      time curve was associated with serum creatinine and estimated glomerular
      filtration rate. CONCLUSIONS: Peak plasma and urinary platinum concentrations and
      pharmacokinetic parameters were associated with risk of subclinical cisplatin
      induced kidney injury as assessed using novel urinary biomarkers. Future studies
      will examine these relationships in larger clinical populations of cisplatin
      induced acute kidney injury.

PMID- 30220073
TI  - Quality of life related to clinical features in patients with Rett syndrome and
      their parents: a systematic review.
AB  - Patients with a neurodevelopmental disorder such as Rett syndrome (RS), as well
      as their families, have complex needs that affect their quality of life (QoL).
      Therefore, both families and patients with RS must be provided with
      multidisciplinary health care that can identify the clinical features that most
      affect their QoL and mental health risks. The main objective of this paper is to
      provide a comprehensive overview of the QoL subdimensions of families affected by
      RS, including both the parents and children. We conducted a systematic review,
      following PRISMA criteria, of the data in the PubMed, PsycINFO, Cuiden, and
      LILACS databases. The results indicated that when considering the family as a
      whole, RS equally affects the physical and psychological QoL dimensions; the next
      most affected was the social dimension. According to parents' reports, seizures
      are one of the main factors that decreases their QoL. Thus, from a clinical point
      of view, controlling seizure activity of children with RS is the main way of
      improving the QoL of their parents. Interventions in patients affected by RS
      should be based on the improvement of visual contact and concentration, reducing
      somnolence, and increasing mobility. The subdimensions of QoL that were most
      affected in parents of girls with RS were those related to mental health and
      feelings of well-being.

PMID- 30220075
TI  - Changes in mental health service use among 8-year-old children: a 24-year time
      trend study.
AB  - The use of children's mental health services has increased, but most children
      with psychiatric problems are still not in contact with these services. This time
      trend study assessed changes in considered and reported service use over a 24
      year period and studied the factors associated with it using four cross-sectional
      studies. Information was gathered on 8-year-old children living in the area
      covered by Turku University Hospital, Finland, at four time points: 986 children
      in 1989, 891 in 1999, 930 in 2005, and 942 in 2013. The same study design,
      methods and school districts were used each year and the participation rates
      varied between 86 and 95%. Parents and teachers completed questionnaires
      concerning the child's psychiatric symptoms and service use. The considered and
      reported service use increased continuously during the study period. In 1989,
      2.4% of children had used services and in 2013 this was 11.0% (OR 5.0, 95% CI 3.1
      8.0). Reported service use also increased among children with comorbid problems,
      from 18.3 to 50.7% (OR 5.0, 95% CI 2.1-12.0). Psychiatric problems and some
      family factors were associated with service use, but the increase was not
      explained by these factors. The increase in child mental health service use may
      reflect better public awareness of mental health problems, fewer barriers to
      accessing care and decrease of stigma. Although more children are using mental
      health services, there are still a large number of children with mental health
      problems who have not been in contact with services.

PMID- 30220074
TI  - Obesity and Sexual Functioning.
AB  - PURPOSE OF THE REVIEW: Sexual functioning is an important, yet often overlooked,
      aspect of quality of life for many individuals with obesity. RECENT FINDINGS:
      With the growing recognition of obesity as a significant, international public
      health issue, a developing body of research has investigated the relationship
      between obesity and sexual functioning. Several studies have found that obesity
      is associated with impairments in sexual functioning. The mechanisms of this
      relationship, whether physiological, psychosocial, or a combination of the two,
      are yet to be fully elucidated. Other studies have suggested that weight loss,
      whether induced by bariatric surgery or less intensive interventions, is
      associated with significant and clinically meaningful change in sexual
      functioning and relevant reproductive hormones. This chapter reviews the research
      in these areas and provides recommendations for future research on these
      relationships.

PMID- 30220076
TI  - Sleep apnea may be associated with suicidal ideation in adolescents.
AB  - Suicide is a major threat to adolescent health. Sleep problems increase the risk
      of adolescent suicidal behavior, but the role of sleep-disordered breathing
      (e.g., sleep apnea) is unclear. We investigated whether sleep apnea had an effect
      on suicidal ideation that was independent of depression and perceived stress. We
      examined a series of sleep variables with suicidal ideation in 746 fifth and
      seventh graders using self-reported questionnaires to assess time in bed, sleep
      quality, insomnia, and sleep apnea while controlling depression and perceived
      stress. Overall, 8.8% of students aged 10-14 years reported having recent
      suicidal ideation, and 33% or 3.8%, depending on the screening criteria, reported
      having suspected sleep apnea. The sleep variables were all associated with an
      increased risk of suicidal ideation, but the magnitude of effects was largely
      attenuated when depression and perceived stress were included in the models.
      Suspected sleep apnea using daytime sleepiness as a screening criterion was
      independently associated with suicidal ideation (odds ratio = 2.25, p < 0.05).
      Suspected sleep apnea was associated with suicidal ideation that was partly
      independent of depression and stress, which reveals the pertinence of screening
      for sleep apnea among school students and designing proper prevention strategies
      for reducing youth suicidal behavior.

PMID- 30220077
TI  - The predictive validity of the Strengths and Difficulties Questionnaire for child
      attention-deficit/hyperactivity disorder.
AB  - We need accurate screening measures for attention-deficit/hyperactivity disorder
      (ADHD) to ensure that children with the disorder are referred for assessment
      without raising concern for children with normal behaviour. The Strengths and
      Difficulties Questionnaire (SDQ) provides hyperactivity-inattention (HI),
      conduct, emotional and peer problem subscales and impact scores that may be used
      for screening. The aim of the study was to investigate the predictive validity of
      the Danish version of the parent SDQ HI subscale at the child age of 7 years for
      subsequent clinically diagnosed ADHD (age 8-15 years). Participants were part of
      the Danish National Birth Cohort (N = 51,096), and children with ADHD were
      identified through the Danish National Health registries (n = 943). Receiver
      operating characteristic analysis showed that the screening accuracy for the HI
      scores was good (area under the curve = .84). With Cox multivariate regression
      analysis, we found that SDQ HI subscale scores >= 7 with impact gave a nearly 14
      fold [hazard ratio (HR) = 13.59] increased risk for ADHD, while conduct and
      emotional problems indicated low risk (HRs of 1.62 and 1.67, respectively). For
      the HI subscale to be a sensitive measure for ADHD, a low cutoff (4) was needed,
      but gave many false screening positives (PPV = .02). Although the diagnostic
      accuracy of the parent version of the SDQ HI subscale for predicting ADHD was
      good, our results question the feasibility of screening the general child
      population for ADHD with only the parent SDQ HI subscale.

PMID- 30220078
TI  - Polycyclic aromatic hydrocarbons (PAHs) in agricultural soils from Ningde, China:
      levels, sources, and human health risk assessment.
AB  - Soil-bound polycyclic aromatic hydrocarbons (PAHs) in farmland are critical to
      human health. The level, composition, source, and cancer risk of sixteen PAHs in
      agricultural soil from Ningde, China, were investigated. The results indicated
      that the total concentrations of 16 PAHs ranged from 77.3 to 1188 ng g-1, with a
      mean value of 406 ng g-1. Five-ring PAHs were found to have the highest
      concentrations (148 +/- 133 ng g-1), followed by four-ring (120 +/- 101 ng g-1),
      three-ring (61.9 +/- 54.2 ng g-1), six-ring (44.6 +/- 61.0 ng g-1), and two-ring
      (31.3 +/- 31.0 ng g-1). Employing positive matrix factorization (PMF), four PAH
      sources including biomass burning (36.3%), coal combustion (35.5%), traffic
      emissions (16.4%), and coke source (11.8%) were identified. Incremental lifetime
      cancer risk (ILCR) results showed that ILCR values ranged from 7.1 * 10-4 to 1.1
      * 10-3, which will cause moderate-to-high cancer risk to human health mainly via
      the soil ingestion and dermal contact exposure pathways. The source-oriented
      results indicated that coal combustion (32.7%), traffic emission (34.3%), and
      biomass burning (32.4%) had similar contributions to the total cancer risk.
      Therefore, more attention should be paid to these pyrolysis-originated sources to
      protect humanity from the health risk of PAHs.

PMID- 30220079
TI  - Remission of fibrosis: rage to the rescue.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive and
      permanent decline of lung function that eventually leads to expiry. A study
      published in 2017 performed by Kumar et al. revealed that the disease may not be
      as irreversible as was once believed. The research discovered a novel role for
      the receptor for advanced glycation end-products (RAGE) in which it acts as a
      master regulator for DNA double-strand break repair. In doing so, Kumar et al.
      may have made a breakthrough that could redefine the translational approaches of
      IPF.

PMID- 30220080
TI  - Optimization of parthenogenetic activation of rabbit oocytes and development of
      rabbit embryo by somatic cell nuclear transfer.
AB  - The present study explored a suitable parthenogenetic activation (PA) procedure
      for rabbit oocytes and investigated the developmental potential of somatic cell
      nuclear transfer (SCNT) embryos using rabbit foetal fibroblasts (RFFs). The
      electrical activation had the optimal rate of blastocyst (14.06%) when oocytes
      were activated by three direct current (DC) pulses (40 V/mm, 20 MUs each)
      followed by 6-dimethylaminopurine (6-DMAP) and cycloheximide (CHX) treatment; the
      blastocyst rate of ionomycin (ION) + 6-DMAP + CHX (12.07%) activation was higher
      than that of ION + 6-DMAP (8.6%) activation or ION + CHX (1.24%) activation;
      there was no significant difference in blastocyst rate between ION + 6-DMAP + CHX
      and DC + 6-DMAP + CHX groups. The blastocyst rate of ION + 6-DMAP + CHX-activated
      oocytes in the basic rabbit culture medium (M-199) + 10% foetal bovine serum
      (FBS; 14.28%) was higher than that in buffalo conditioned medium (5.75%) or G1/G2
      medium (0), and the blastocyst rate was increased when M-199 + 10% FBS was
      supplemented with amino acids. Refreshing culture medium every day or every other
      day significantly increased the blastocyst rate. Treatment of donor cells with
      0.5% FBS for 3-5 days increased blastocyst rate of SCNT embryos (33.33%) than no
      serum starvation (22.47%) or 0.5% FBS treatment for 6-9 days (23.61%); the
      blastocyst rate of SCNT embryos derived from nontransgenic RFFs was higher than
      that derived from transgenic RFFs by electroporation. The blastocyst development
      ability of SCNT embryos derived from RFFs by electroporation (32.22%) was higher
      than that of liposome (19.11%) or calcium phosphate (20.00%) transfection, and
      only the embryos from electroporation group have the EGFP expression (24.44%). In
      conclusion, this study for the first time systematically optimized the conditions
      for yield of rabbit embryo by SCNT.

PMID- 30220082
TI  - New Food and Drug Administration-Approved and Emerging Novel Treatment Options
      for Acute Myeloid Leukemia.
AB  - Advancements in the treatment of acute myeloid leukemia (AML) have been sparse
      during the past several decades, and the disease continues to have a poor
      prognosis. However, in 2017 alone, four new medications approved by the U.S. Food
      and Drug Administration (FDA) for the treatment of AML reached the market.
      Midostaurin, liposomal cytarabine and daunorubicin, enasidenib, and gemtuzumab
      ogozamicin all showed benefit in respective clinical trials to gain approval for
      the treatment of AML in various patient populations. Additionally, many phase II
      and III clinical trials are currently ongoing to assess the safety and efficacy
      of other potential therapies for the treatment of AML. In this review, we
      summarize the results of the landmark clinical trials associated with the newly
      approved agents as well as the current ongoing clinical trials for the treatment
      of AML. A literature search was performed to retrieve data on agents currently
      being studied for use. Although the overall prognosis for patients with AML
      remains poor, the addition of the newly FDA-approved medications is a step in the
      right direction for a disease state that has proved difficult to treat.

PMID- 30220081
TI  - Adenosine A2A receptors facilitate synaptic NMDA currents in CA1 pyramidal
      neurons.
AB  - BACKGROUND AND PURPOSE: NMDA receptors play a key role in both synaptic
      plasticity and neurodegeneration. Adenosine is an endogenous neuromodulator and
      through membrane receptors of the A2A subtype can influence both synaptic
      plasticity and neuronal death. The present work was designed to evaluate the
      influence of adenosine A2A receptors upon NMDA receptor activity in CA1
      hippocampal neurons. We discriminated between modulation of synaptic versus
      extrasynaptic receptors, since extrasynaptic NMDA receptors are mostly associated
      with neurodegeneration while synaptic NMDA receptors are linked to plasticity
      phenomena. EXPERIMENTAL APPROACH: Whole-cell patch-clamp recordings were obtained
      to evaluate NMDA receptor actions on CA1 pyramidal neurons of young adult (5-10
      weeks) male Wistar rat hippocampus. KEY RESULTS: Activation of A2A receptors with
      CGS 21680 (30 nM) consistently facilitated chemically-evoked NMDA receptor
      currents (NMDA-PSCs) and afferent-evoked NMDA-currents (NMDA-EPSCs), an action
      prevented by an A2A receptor antagonist (SCH58261, 100 nM) and a PKA inhibitor, H
      89 (1 MUM). These actions did not reflect facilitation in glutamate release since
      there was no change in NMDA-EPSCs paired pulse ratio. A2A receptor actions were
      lost in the presence of an open-channel NMDA receptor blocker, MK-801 (10 MUM),
      but persisted in the presence of memantine, at a concentration (10 MUM) known to
      preferentially block extrasynaptic NMDA receptors. CONCLUSION AND IMPLICATIONS:
      These results show that A2A receptors exert a positive postsynaptic modulatory
      effect over synaptic, but not extrasynaptic, NMDA receptors in CA1 neurons and,
      therefore, under non-pathological conditions may contribute to shift the dual
      role of NMDA receptors towards enhancement of synaptic plasticity.

PMID- 30220083
TI  - VSIG-3 as a ligand of VISTA inhibits human T-cell function.
AB  - B7 family members and their receptors play a central role in the regulation of T
      cell responses through T-cell co-stimulation and co-inhibition pathways that
      constitute attractive targets for the development of immunotherapeutic drugs. In
      this study, we report that VSIG-3/IGSF11 is a ligand of B7 family member VISTA/PD
      1H and inhibits human T-cell functions through a novel VSIG-3/VISTA pathway. An
      extensive functional ELISA binding screening assay reveals that VSIG-3 binds to
      the new B7 family member VISTA but does not interact with other known members of
      the B7 family. Under the same experimental conditions, we did not observe any
      significant interaction between VSIG-8 and VISTA. In addition, VSIG-3 inhibits
      human T-cell proliferation in the presence of T-cell receptor signaling.
      Furthermore, VSIG-3 significantly reduces cytokine and chemokine production by
      human T cells including IFN-gamma, IL-2, IL-17, CCL5/Rantes, CCL3/MIP-1alpha, and
      CXCL11/I-TAC. Anti-VISTA neutralization antibodies attenuate the binding of VSIG
      3 and VISTA, as well as VSIG-3-induced T-cell inhibition. Hence, we have
      identified a novel ligand for VISTA that is able to inhibit human T-cell
      proliferation and cytokine production. This unique VSIG-3/VISTA co-inhibitory
      pathway may provide new strategies for the treatment of human cancers, autoimmune
      disorders, infection, and transplant rejection and may aid in the design of
      better vaccines.

PMID- 30220084
TI  - Targeting the ICOS/ICOS-L pathway in a mouse model of established allergic asthma
      disrupts T follicular helper cell responses and ameliorates disease.
AB  - BACKGROUND: Allergic asthma is characterized by chronic inflammation and
      remodelling of the airways, associated with dysregulated type 2 immune responses
      and allergen-specific IgE. T follicular helper cells (TFH ) are crucial in T
      dependent B-cell responses and have been implicated in allergic airway disease
      (AAD). TFH , unlike other CD4+ T cells, are uniquely reliant on continuous ICOS
      signalling to maintain their phenotype after T-cell priming; therefore,
      disrupting this signal can impair TFH responses. However, the contribution of TFH
      to disease during chronic aero-allergen exposure and the therapeutic potential of
      targeting these cells have not been evaluated. METHODS: To establish AAD, female
      BALB/c mice were repeatedly exposed to house dust mite or Alternaria alternata
      three times a week for up to 5 weeks. To examine the impact of TFH on AAD, mice
      were allergen exposed for 5 weeks and co-administered anti-ICOS Ligand-targeted
      antibodies, three times a week for the last 2 weeks. RESULTS: TFH were first
      observed in the lung-draining lymph nodes and with further exposure were also
      found locally within the lungs. TFH accumulated with sustained allergen exposure,
      alongside germinal centre (GC) B cells. Blockade of ICOS signalling after AAD
      establishment successfully depleted TFH but did not affect the differentiation of
      other CD4+ T-cell subsets. This reduced GC responses, allergen-specific IgE,
      inflammation, pulmonary IL-13 and airway hyper-responsiveness. CONCLUSIONS: TFH
      are crucial in the regulation of AAD and the ICOS/ICOS-L pathway could represent
      a novel therapeutic target in allergic asthma.

PMID- 30220085
TI  - Technical Note: Characterization of clinical linear accelerator triggering
      latency for motion management system development.
AB  - PURPOSE: Latencies for motion management systems have previously been presented
      as guidelines for system development and implementation. These guidelines
      consider the overall system latency, including data acquisition, algorithm
      processing, and linac triggering time. However, during system development, the
      triggering latency of the clinical linear accelerator is often considered fixed.
      This paper presents a method to decouple the linac-only triggering latency from
      the total system latency such that latency can be considered in terms of only the
      linac-independent aspects of the system. METHODS: The linac-only latency was
      investigated by considering the time at which a linac response was observed
      relative to the time at which a beam-on/off triggering signal was sent to the
      linac. The relative time between the two signals was analyzed using a
      multichannel oscilloscope with input signals from a custom gating box to manually
      trigger the beam state as well as a diode positioned at beam isocenter to monitor
      the linac response. The beam-on/off latency was measured at multiple energies
      (6/18 MV) and repetition rates (100-600 MU/min) to investigate beam setting
      dependencies. RESULTS: The measured latency was observed to be dependent on the
      accelerator settings for repetition rate and energy, with beam-on latencies
      decreasing with increasing repetition rate and decreasing energy. In contrast,
      the opposite trend was present for the observed beam-off latency. At 600 MU/min,
      beam-on/off latencies were observed to be 3.37/1.45 ms for a 6 MV beam and
      6.02/0.73 ms for an 18 MV beam. Negative latencies were possible for beam-off
      measurements due to the mechanical latency being less than the pulse separation
      at given repetition rates. CONCLUSIONS: The linac latency associated with
      triggering the beam-on/off was determined to have a minor contribution to the
      total allowable system latency; thus, the majority of the total system latency
      can be attributed to linac-independent factors.

PMID- 30220087
TI  - Agitated saline contrast echocardiography reveals cor triatriatum dexter.
AB  - We present the case of a 54-year-old man who had an unusual finding in contrast
      echocardiography with agitated saline. Partition of the right atrium in two
      compartments, an opacified and a non-opacified one, was noted. Further assessment
      with a transesophageal echocardiogram revealed the presence of a membrane in the
      right atrium, with the final diagnosis being cor triatriatum dexter.

PMID- 30220086
TI  - Elevated end-diastolic wall stress after acute myocardial infarction predicts
      adverse cardiovascular outcomes and longer hospital length of stay.
AB  - BACKGROUND: Acute myocardial infarction (MI) leads to ventricular remodeling in
      response to oxygen demand. Such changes include left ventricular (LV) dilatation
      and increased myocardial wall stress. Prior studies showed that wall stress is a
      vital parameter of cardiac remodeling. However, outcome data are lacking. We aim
      to investigate wall stress post-MI in relation to biomarkers of cardiac
      remodeling and cardiovascular outcomes. METHODS: Patients presenting with ST
      elevation MI (STEMI) requiring primary percutaneous intervention (PCI) were
      enrolled prospectively. LVEF and volume-based end-diastolic (EDWS) and end
      systolic (ESWS) wall stress were measured from predischarge echocardiograms.
      Serum samples were collected for measurement of serum biomarkers. We identified
      81 patients meeting inclusion criteria (64% men, 36% women) with a mean age of
      61. The primary outcome was major adverse cardiovascular events (MACE) defined as
      1-year composite endpoint of cardiac mortality, recurrent MI, revascularization,
      or stroke. Length of hospitalization (LOH) was recorded. RESULTS: Major adverse
      cardiovascular events-positive patients (n = 12) had significantly higher EDWS
      levels (15.87 vs 12.33, P = 0.045), and galectin-3 levels (19.07 vs 11.75, P =
      0.015), and lower LVEF (40.0% vs 48.4%, P = 0.023) compared to MACE-negative
      patients. Patients with LOH > 72 hours (n = 33) had significantly higher EDWS,
      galectin-3, and peak troponin, and lower LVEF compared to patients with LOH < 72
      hours. EDWS positively correlated with LOH and galectin-3. EDWS was an
      independent predictor of MACE by binomial regression analysis. CONCLUSION: End
      diastolic walls tress is a potential prognostic tool for risk stratifying STEMI
      patients, providing an assessment of the functional consequences of myocardial
      remodeling. It is predictive of MACE independent of LVEF, associated with longer
      hospitalizations, and correlates with galectin-3, a biomarker of cardiac
      remodeling.

PMID- 30220088
TI  - The sialyltransferase ST3Gal3 facilitates the receptivity of the uterine
      endometrium in vitro and in vivo.
AB  - The receptive uterine endometrium specifically expresses certain
      glycosyltransferases, and the corresponding oligosaccharides play important roles
      in accepting the embryo. The sialyltransferase beta-galactoside-alpha2,3
      sialyltransferase III (ST3Gal3) is the key enzyme responsible for sialyl Lewis X
      (sLeX) oligosaccharide biosynthesis, but the expression and function of ST3Gal3
      in the receptive endometrium is still elusive. Here, we found that human
      endometrial tissues at secretory phase expressed a 4-fold higher ST3Gal3 level
      relative to the tissues at proliferative phase. Meanwhile, downregulation of
      ST3Gal3 or sLeX epitope blockage significantly impaired the receptive ability of
      human endometrial RL95-2 cells to trophoblastic cells in vitro and inhibited
      implantation in pregnant mice. This study suggests that ST3Gal3 facilitates
      endometrial receptivity through increasing sLeX oligosaccharide, which gives a
      better understanding of the glycobiology of implantation.

PMID- 30220089
TI  - The p33 protein of Citrus tristeza virus affects viral pathogenicity by
      modulating a host immune response.
AB  - Accumulation of reactive oxygen species (ROS) is a general plant basal defense
      strategy against viruses. In this study, we show that infection by Citrus
      tristeza virus (CTV) triggered ROS burst in Nicotiana benthamiana and in the
      natural citrus host, the extent of which was virus-dose dependent. Using
      Agrobacterium-mediated expression of CTV-encoded proteins in N. benthamiana, we
      found that p33, a unique viral protein, contributed to the induction of ROS
      accumulation and programmed cell death. The role of p33 in CTV pathogenicity was
      assessed based on gene knockout and complementation in N. benthamiana. In the
      citrus-CTV pathosystem, deletion of the p33 open reading frame in a CTV variant
      resulted in a significant decrease in ROS production, compared to that of the
      wild type CTV, which correlated with invasion of the mutant virus into the
      immature xylem tracheid cells and abnormal differentiation of the vascular
      system. By contrast, the wild type CTV exhibited phloem-limited distribution with
      a minor effect on the vasculature. We conclude that the p33 protein is a CTV
      effector that negatively affects virus pathogenicity and suggest that N.
      benthamiana recognizes p33 to activate the host immune response to restrict CTV
      into the phloem tissue and minimize the disease syndrome.

PMID- 30220090
TI  - Resynchronization with the G6G protocol: A retrospective, observational study of
      second and later timed artificial inseminations on commercial dairy farms.
AB  - We recorded conception rates and estimated pregnancy rates following second and
      later timed artificial inseminations (TAIs) after hormonal resynchronization on
      commercial dairy farms, using the so-called G6G protocol (PGF day-0; GnRH 2, 8
      days; PGF 15, 16 days, GnRH 17 days; TAI 18 days), and the 5-day Ovsynch protocol
      or 5DO (GnRH day 0; PGF 5, 6 days; GnRH 7 days; TAI 8 days). In four farms, both
      protocols were implemented in parallel, and these 1,368 s and later TAIs were
      used for the protocols' comparison based on logistic regression (544 TAIs in
      primiparous; 824 in multiparous cows; 1,024 TAIs after G6G [600 TAIs in
      multiparous and 424 in primiparous]; 344 TAIs after 5DO [224 TAIs in multiparous
      and 120 in primiparous]; 280 TAIs during the hot season; 1,088 during the cool
      season). Conception rate (CR) was 31.7% +/- 12.0% among all cows, 35.1% +/- 10.7%
      among cows resynchronized with the G6G protocol and 21.8% +/- 9.7% among cows
      resynchronized with the 5DO protocol (p < 0.0001). CR among all cows was lower
      during the hot season (19.3% +/- 8.4%) than during the cool season (34.9% +/-
      10.6%; p < 0.0001), and similar seasonal results were observed with G6G
      protocols. Logistic regression showed significant effects on CR in second and
      later TAIs by protocol (OR = 0.514; 95% CI 0.385-0.686; p < 0.0001) and season
      (OR = 0.486; 95% CI 0.350-0.676; p < 0.0001). Parity did not influence CR after
      second and later TAIs (p > 0.1), and no interaction with season or
      resynchronization protocol was found. Estimated pregnancy rates based on these CR
      data from both hormonal protocols suggest that G6G can be effectively used for
      second and later TAIs and highlight the importance of considering protocol and
      season when designing strategies for second and later timed AIs on dairy farms.

PMID- 30220091
TI  - Parental transposable element loads influence their dynamics in young Nicotiana
      hybrids and allotetraploids.
AB  - The genomic shock hypothesis suggests that allopolyploidy is associated with
      genome changes driven by transposable elements, as a response to imbalances
      between parental insertion loads. To explore this hypothesis, we compared three
      allotetraploids, Nicotiana arentsii, N. rustica and N. tabacum, which arose over
      comparable time frames from hybridisation between increasingly divergent diploid
      species. We used sequence-specific amplification polymorphism (SSAP) to compare
      the dynamics of six transposable elements in these allopolyploids, their diploid
      progenitors and in corresponding synthetic hybrids. We show that element-specific
      dynamics in young Nicotiana allopolyploids reflect their dynamics in diploid
      progenitors. Transposable element mobilisation is not concomitant with immediate
      genome merger, but occurs within the first generations of allopolyploid
      formation. In natural allopolyploids, such mobilisations correlate with
      imbalances in the repeat profile of the parental species, which increases with
      their genetic divergence. Other restructuring leading to locus loss is immediate,
      nonrandom and targeted at specific subgenomes, independently of cross
      orientation. The correlation between transposable element mobilisation in
      allopolyploids and quantitative imbalances in parental transposable element loads
      supports the genome shock hypothesis proposed by McClintock.

PMID- 30220092
TI  - Unnecessary harm is avoided by reliable paediatric index of mortality2 scores
      without arterial gas sampling.
AB  - AIM: To investigate whether unnecessary harm could be avoided in children
      admitted to paediatric intensive care (PICU), we analysed the impact of arterial
      blood gas on the paediatric index of mortality score2 (PIM2) and the derived
      predicted death rate (PDR). METHODS: From January 1, 2008 to December 31, 2010,
      1793 consecutive admissions, newborn infants to 16 years of age (median 0.71
      years) from a single, tertiary PICU in Gothenburg Sweden, were collected.
      Admission information on arterial oxygen tension (PaO2 ) and fraction of inspired
      oxygen (FiO2 ) was extracted from 990 admissions. RESULTS: There was close
      agreement between PIM2 score and PDR regardless of whether the PaO2 /FiO2 ratio
      was omitted or not. In the subgroup of admissions with a respiratory admission
      diagnosis, the inclusion of the PaO2 /FiO2 ratio increased the accuracy of the
      PIM2 score as well as the PDR. The standard mortality ratio was slightly but not
      significantly overestimated by excluding the PaO2 /FiO2 ratio. CONCLUSION: To
      avoid unnecessary harm to children admitted to PICU, an arterial blood gas
      analysis should only be performed if clinically indicated or if the child has a
      respiratory admission diagnosis. Estimation of the PIM2 score and PDR will not be
      less accurate by this approach.

PMID- 30220093
TI  - Penetration of sodium hypochlorite into root canal dentine: effect of
      surfactants, gel form and passive ultrasonic irrigation.
AB  - AIM: To assess the penetration of sodium hypochlorite (NaOCl) gel or NaOCl
      solutions with surfactants, and the effect of passive ultrasonic irrigation (PUI)
      on penetration into dentinal tubules. METHODOLOGY: Bovine incisor root canals
      were instrumented, the roots sectioned and the dentine blocks obtained were
      stained with crystal violet. Dentine blocks (n = 10 per group) were exposed to 3%
      NaOCl gel or 3% NaOCl solution for 10 and 20 min. Other dentine blocks (n = 10
      per group) were exposed to Chlor-Extra (6% NaOCl + surfactant), 6% NaOCl, 2.5%
      NaOCl with 0.2% cetrimide and 2.5% NaOCl for 10 and 20 min. The penetration depth
      of irrigants into dentinal tubules was measured in micrometres by viewing the
      bleached crystal violet under a stereomicroscope. Additionally, bovine incisor
      root canals, instrumented and stained with crystal violet, were distributed into
      two groups (n = 10) and irrigated with 2.5% NaOCl with PUI or conventional
      syringe irrigation (CSI). The penetration depth of irrigants into dentinal
      tubules was assessed 3 and 7 mm from the apex. Statistical analysis was performed
      by ANOVA and Tukey tests (alpha = 0.05). RESULTS: There was significantly greater
      penetration of 3% NaOCl solution into dentinal tubules compared with the gel form
      (P < 0.05). There was no difference (P > 0.05) between 6% NaOCl and Chlor-Extra,
      and between 2.5% NaOCl and 2.5% NaOCl + cetrimide. PUI significantly increased
      the penetration depth of NaOCl into dentinal tubules when compared with CSI (P <
      0.05). CONCLUSIONS: In extracted bovine incisors, NaOCl gel penetrated less into
      dentinal tubules than NaOCl solution. The addition of surfactants did not
      increase the penetration depth. The use of PUI significantly increased NaOCl
      penetration into dentinal tubules.

PMID- 30220094
TI  - Managing the hope and worry of housing renewal-supporting well-being in the
      emerging community.
AB  - ISSUE ADDRESSED: Housing renewal is a common urban housing and development
      strategy internationally. An intended result is increased social inclusion and
      well-being of residents through public housing de-concentration. In this study,
      we examined challenges encountered during the process of housing renewal from the
      perspectives of community-based staff and volunteers. METHODS: We conducted semi
      structured qualitative interviews with housing and community workers, service
      managers and community volunteers who were working with residents experiencing
      housing renewal in an outer metropolitan estate in New South Wales. We analysed
      the data thematically. RESULTS: Seventeen participants were interviewed in a mix
      of individual and group interviews. Housing workers uncovered substantial
      resident health and social support needs during housing assessments. Promoting
      access to services and supporting the mental health and social connectedness of
      residents into the future were seen as key goals and challenges. However, lack of
      clarity on which services and community resources would exist in the new
      neighbourhood at the completion of the renewal project made this more difficult,
      particularly when supporting the social housing residents who were remaining in
      the changing community. CONCLUSIONS: Supporting the mental health and well-being
      of residents experiencing housing renewal is an important role of community-based
      workers, volunteers and service providers. This includes facilitating access to
      health care and other services and promoting social connectedness in the emerging
      community. Increased clarity on what community resources and services will be
      available subsequent to redevelopment will assist in these aims. SO WHAT?: Early
      knowledge of what community resources and services will be in place long term in
      communities undergoing housing renewal will allow staff and volunteers to better
      support the health and well-being of residents.

PMID- 30220095
TI  - Zinc finger nuclease-mediated targeting of multiple transgenes to an endogenous
      soybean genomic locus via non-homologous end joining.
AB  - Emerging genome editing technologies hold great promise for the improvement of
      agricultural crops. Several related genome editing methods currently in
      development utilize engineered, sequence-specific endonucleases to generate DNA
      double strand breaks (DSBs) at user-specified genomic loci. These DSBs
      subsequently result in small insertions/deletions (indels), base substitutions or
      incorporation of exogenous donor sequences at the target site, depending on the
      application. Targeted mutagenesis in soybean (Glycine max) via non-homologous end
      joining (NHEJ)-mediated repair of such DSBs has been previously demonstrated with
      multiple nucleases, as has homology-directed repair (HDR)-mediated integration of
      a single transgene into target endogenous soybean loci using CRISPR/Cas9. Here we
      report targeted integration of multiple transgenes into a single soybean locus
      using a zinc finger nuclease (ZFN). First, we demonstrate targeted integration of
      biolistically delivered DNA via either HDR or NHEJ to the FATTY ACID DESATURASE 2
      1a (FAD2-1a) locus of embryogenic cells in tissue culture. We then describe ZFN-
      and NHEJ-mediated, targeted integration of two different multigene donors to the
      FAD2-1a locus of immature embryos. The largest donor delivered was 16.2 kb,
      carried four transgenes, and was successfully transmitted to T1 progeny of mature
      targeted plants obtained via somatic embryogenesis. The insertions in most plants
      with a targeted, 7.1 kb, NHEJ-integrated donor were perfect or near-perfect,
      demonstrating that NHEJ is a viable alternative to HDR for gene targeting in
      soybean. Taken together, these results show that ZFNs can be used to generate
      fertile transgenic soybean plants with NHEJ-mediated targeted insertions of
      multigene donors at an endogenous genomic locus.

PMID- 30220096
TI  - Removal of soil biota alters soil feedback effects on plant growth and defense
      chemistry.
AB  - We examined how the removal of soil biota affects plant-soil feedback (PSF) and
      defense chemistry of Jacobaea vulgaris, an outbreak plant species in Europe
      containing the defense compounds pyrrolizidine alkaloids (PAs). Macrofauna and
      mesofauna, as well as fungi and bacteria, were removed size selectively from
      unplanted soil or soil planted with J. vulgaris exposed or not to above- or
      belowground insect herbivores. Wet-sieved fractions, using 1000-, 20-, 5- and 0.2
      MUm mesh sizes, were added to sterilized soil and new plants were grown. Sieving
      treatments were verified by molecular analysis of the inocula. In the feedback
      phase, plant biomass was lowest in soils with 1000- and 20-MUm inocula, and soils
      conditioned with plants gave more negative feedback than without plants.
      Remarkably, part of this negative PSF effect remained present in the 0.2-MUm
      inoculum where no bacteria were present. PA concentration and composition of
      plants with 1000- or 20-MUm inocula differed from those with 5- or 0.2-MUm
      inocula, but only if soils had been conditioned by undamaged plants or plants
      damaged by aboveground herbivores. These effects correlated with leaf
      hyperspectral reflectance. We conclude that size-selective removal of soil biota
      altered PSFs, but that these PSFs were also influenced by herbivory during the
      conditioning phase.

PMID- 30220097
TI  - Non-atopic rhinitis at age 6 is associated with subsequent development of asthma.
AB  - BACKGROUND: It has been postulated that the association between allergic rhinitis
      and asthma is attributable to the progressive clinical expression of respiratory
      inflammation during childhood. The role of non-allergic rhinitis in early life in
      relation to subsequent asthma has not been extensively explored. OBJECTIVE: We
      sought to determine whether rhinitis in early life was associated with risk of
      asthma development into adulthood, and whether this relationship is independent
      of allergic sensitization. METHODS: Participants were identified from the Tucson
      Children's Respiratory Study, a non-selected birth cohort. Allergy skin prick
      testing was performed at age 6 years using house dust mix, Bermuda, mesquite,
      olive, mulberry, careless weed, and Alternaria aeroallergens. Atopy was defined
      as >=1 positive tests. Physician-diagnosed active asthma from age 6 to 32 and
      physician-diagnosed rhinitis at age 6 were determined by questionnaire.
      Participants with asthma or active wheezing at age 6 were excluded from analyses.
      Risk estimates were obtained with Cox regression. RESULTS: There were 521
      participants who met inclusion criteria. The hazard ratio for subsequently
      acquiring a diagnosis of asthma between the ages of 8 and 32 for those with non
      atopic rhinitis was 2.1 (95% CI: 1.2, 3.4, P = 0.005), compared with the non
      atopic no rhinitis group, after adjusting for sex, ethnicity, maternal asthma,
      maternal education and smoking, and history of 4+ colds per year at age 6. Among
      the atopic participants, both the active and no rhinitis groups were more likely
      to develop and have asthma through age 32. The relation between non-atopic
      rhinitis and asthma was independent of total serum IgE levels at age 6.
      CONCLUSION AND CLINICAL RELEVANCE: Childhood rhinitis, even in the absence of
      atopy, confers significant risk for asthma development through adulthood. These
      findings underscore the importance of non-allergic mechanisms in the development
      of asthma.

PMID- 30220098
TI  - Flow cytometric quantitation of EpCAM-positive extracellular vesicles by
      immunomagnetic separation and phospholipid staining method.
AB  - Extracellular vesicles (EV) have attracted attention as circulating biomarkers
      for many diseases, particularly cancer. Conventional immunofluorescence staining
      has been used for the detection of target antigens on EV by flow cytometry.
      However, the staining intensity depends on the amount of antigen expressed on the
      vesicles and is often only around the noise level. Instead of immunofluorescence,
      we combined immunomagnetic separation using nanosize MACS(r) MicroBeads with
      phospholipid staining of EV (IMS-PS method). EpCAM-positive EV were prepared from
      the culture supernatants of OVCAR3 (EpCAM-high), A431 (EpCAM-low) or Colon-26
      (non-human control) cells as cancer models and were examined by the IMS-PS method
      using EpCAM mAb-coated MicroBeads. By employing Polaric-500c6F as the dye for
      staining EV phospholipids and using appropriate flow cytometry settings,
      autofluorescence was excluded, whereas pretreatment of the MicroBeads with
      conventional blocking agents reduced nonspecific binding to non-target vesicles.
      These modifications resulted in a linear relation between the number of EV
      detected and the sample volume, regardless of the level of EpCAM expression on
      the vesicles. A431 EV spiked into healthy volunteer plasma were enumerated with
      good accuracy. The IMS-PS method may be useful for clinical evaluation of EV with
      low levels of antigen expression that are difficult to detect by conventional
      immunofluorescence.

PMID- 30220100
TI  - Influence of meteorological parameters in the seasonality of influenza viruses
      circulating in Northern Cameroon.
AB  - BACKGROUND: Several studies have demonstrated the role of meteorological
      parameters in the seasonality of influenza viruses in tropical and subtropical
      regions, most importantly temperature, humidity and rainfall. OBJECTIVES: This
      study aimed to describe the influence of meteorological parameters in the
      seasonality of influenza viruses in Northern Cameroon, a region characterized by
      high temperatures. METHODS: This was a retrospective study performed in Garoua
      Cameroon from January 2014 to December 2016. Monthly proportions of confirmed
      influenza cases from six sentinel sites were considered as dependent variables,
      whereas monthly values of mean temperature, average relative humidity and
      accumulated rainfall were considered as independent variables. A Vector Error
      Correction Model (VECM) was used to determine the relationship between influenza
      activity and the meteorological variables. RESULTS AND CONCLUSION: Analysis
      showed that there was a statistically significant association between overall
      influenza activity and influenza A activity with respect to average relative
      humidity. A unit increase in humidity within a given month leads to more than 85%
      rise in the overall influenza and influenza A activity two months later.
      Meanwhile, none of the three meteorological variables could explain influenza B
      activity. This observation is essential in filling the gap of knowledge and could
      help in the prevention and control strategies to strengthen influenza
      surveillance program in Cameroon. This article is protected by copyright. All
      rights reserved.

PMID- 30220099
TI  - Prolonged inhibition of hepatocellular carcinoma cell proliferation by
      combinatorial expression of defined transcription factors.
AB  - Hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer
      cases and has an extremely poor prognosis. Therefore, novel innovative therapies
      for HCC are strongly desired. As gene therapy tools for HCC, 2 hepatic
      transcription factors (TF), HNF4A and HNF1A, have been used to suppress
      proliferation and to extinguish cancer-specific characteristics of target cells.
      However, our present data demonstrated that single transduction of HNF4A or HNF1A
      had only a limited effect on suppression of HCC cell proliferation. Thus, in this
      study, we examined whether combinations of TF could show more effective antitumor
      activity, and found that combinatorial transduction of 3 hepatic TF, HNF4A, HNF1A
      and FOXA3, suppressed HCC cell proliferation more stably than single transduction
      of these TF. The combinatorial transduction also suppressed cancer-specific
      phenotypes, such as anchorage-independent growth in culture and tumorigenicity
      after transplantation into mice. HCC cell lines transduced with the 3 TF did not
      recover their proliferative property after withdrawal of anticancer drugs,
      indicating that combinatorial expression of the 3 TF suppressed the growth of all
      cell subtypes within the HCC cell lines, including cancer stem-like cells.
      Transcriptome analyses revealed that the expression levels of a specific gene set
      involved in cell proliferation were only decreased in HCC cells overexpressing
      all 3 TF. Moreover, combined transduction of the 3 TF could facilitate hepatic
      differentiation of HCC cell lines. Our strategy for inducing stable inhibition
      and functional differentiation of tumor cells using a defined set of TF will
      become an effective therapeutic strategy for various types of cancers.

PMID- 30220101
TI  - A scoring system to predict recurrence in patients with differentiated thyroid
      cancer.
AB  - OBJECTIVES: Though predictive models have been constructed to determine the risk
      of recurrence in differentiated thyroid carcinoma, various aspects of these
      models are inadequate. Therefore, we aimed to construct, internally validate and
      implement on a mobile application a scoring system to determine this risk within
      10 years. DESIGN: A retrospective cohort study in 1984-2016. SETTING: A Spanish
      region. PARTICIPANTS: We enrolled 200 patients with differentiated thyroid
      carcinoma without distant metastasis at diagnosis. MAIN OUTCOME MEASURES: Time-to
      recurrence. A risk table was constructed based on the sum of points to estimate
      the likelihood of recurrence. The model was internally validated and implemented
      as a mobile application for Android. RESULTS: Predictive factors were follicular
      histology, T, N and multifocality. This risk table had a C-statistic of 0.723.
      The calibration was satisfactory. CONCLUSIONS: This study provides an instrument
      able to predict rapidly and very simply which patients with differentiated
      thyroid carcinoma have a greater risk of recurrence.

PMID- 30220102
TI  - Prevalence of diabetes and its effects on stroke outcomes: A meta-analysis and
      literature review.
AB  - AIMS/INTRODUCTION: Diabetes mellitus is an established risk factor for stroke and
      maybe associated with poorer outcomes after stroke. The aims of the present
      literature review were to determine: (i) the prevalence of diabetes in acute
      stroke patients through a meta-analysis; (ii) the association between diabetes
      and outcomes after ischemic and hemorrhagic stroke; and (iii) to review the value
      of glycated hemoglobin and admission glucose-based tests in predicting stroke
      outcomes. MATERIALS AND METHODS: Ovid MEDLINE and EMBASE searches were carried
      out to find studies relating to diabetes and inpatient stroke populations
      published between January 2004 and April 2017. A meta-analysis of the prevalence
      of diabetes from included studies was undertaken. A narrative review on the
      associations of diabetes and different diagnostic methods on stroke outcomes was
      carried out. RESULTS: A total of 66 eligible articles met inclusion criteria. A
      meta-analysis of 39 studies (n = 359,783) estimated the prevalence of diabetes to
      be 28% (95% confidence interval 26-31). The rate was higher in ischemic (33%, 95%
      confidence interval 28-38) compared with hemorrhagic stroke (26%, 95% confidence
      interval 19-33) inpatients. Most, but not all, studies found that acute
      hyperglycemia and diabetes were associated with poorer outcomes after ischemic or
      hemorrhagic strokes: including higher mortality, poorer neurological and
      functional outcomes, longer hospital stay, higher readmission rates, and stroke
      recurrence. Diagnostic methods for establishing diagnosis were heterogeneous
      between the reviewed studies. CONCLUSIONS: Approximately one-third of all stroke
      patients have diabetes. Uniform methods to screen for diabetes after stroke are
      required to identify individuals with diabetes to design interventions aimed at
      reducing poor outcomes in this high-risk population.

PMID- 30220103
TI  - Mixotrophic orchids do not use photosynthates for perennial underground organs.

PMID- 30220104
TI  - Predictors of sling revision after mid-urethral sling procedures: a case-control
      study.
AB  - OBJECTIVE: To identify patient characteristics and surgical factors predictive of
      complications requiring mid-urethral sling (MUS) revision/removal. DESIGN: Case
      control study. SETTING: Tertiary academic centre in Canada. POPULATION: One
      hundred and seven women undergoing MUS revision/removal between 2005 and 2016
      were matched with 214 controls by date of index MUS procedure (2:1 ratio).
      METHODS: Data on patient and surgical factors were obtained via manual electronic
      and paper chart review. Three sets of pre-specified simple and multivariable
      logistic regression models were fitted to: (1) examine previously reported risk
      factors for MUS revision after primary surgical treatment; (2) identify
      preoperative predictors of MUS complications requiring revision/removal; and (3)
      identify surgical factors associated with this outcome after adjusting for
      potential confounding factors. MAIN OUTCOME MEASURES: Crude and adjusted odds
      ratios (ORs) with 95% confidence intervals (95% CIs) for patient and surgical
      factors. RESULTS: The median time to MUS revision was 153 days (interquartile
      range, IQR 49-432 days). Active smoking status (OR 2.29, 95% CI 1.13-4.63, P =
      0.03), having had a previous hysterectomy (OR 3.88, 95% CI 2.02-7.46, P < 0.01),
      and undergoing concomitant pelvic organ prolapse surgery at the time of the index
      MUS procedure (OR 2.63, 95% CI 1.32-5.52, P < 0.01) were independently associated
      with the need for MUS revision/removal. Sling type (obturator versus retropubic),
      method of tensioning (to cough versus over instrument), anaesthetic type, and
      estimated blood loss were not associated with this outcome in the analysis
      presented here. CONCLUSIONS: Active smoking status, having had a previous
      hysterectomy, and undergoing concomitant surgery for pelvic organ prolapse are
      risk factors for requiring subsequent MUS revision/removal. TWEETABLE ABSTRACT:
      Risk factors for sling revision include smoking, previous hysterectomy, and
      concomitant prolapse surgery.

PMID- 30220106
TI  - Vascular endothelial dysfunction in the wake of HIV and ART.
AB  - Mounting evidence points to increased rates of cardiovascular disease (CVD) among
      people living with HIV/AIDS (PLWHA). Endothelial dysfunction (loss of endothelium
      dependent vascular relaxation in response to provasodilatory stimuli) constitutes
      an early pathophysiological event in atherogenesis and CVD. Both HIV-1 infection
      and antiretroviral therapy (ART) are implicated in the development of endothelial
      dysfunction; however, conclusions are frequently drawn from associations shown in
      epidemiological studies. In this narrative review of mainly in vitro and animal
      studies, we report on the current understanding of how various HIV-1 proteins,
      HIV-1-induced proinflammatory cytokines and common antiretroviral drugs directly
      impact vascular endothelial cells. Proposed cellular mechanisms underlying the
      switch to a dysfunctional state are discussed, including oxidative stress,
      impaired expression and regulation of endothelial nitric oxide (NO) synthase
      (eNOS) and increased expression of vascular adhesion molecules. From the
      literature, it appears that increased reactive oxygen species (ROS) production,
      linked to decreased NO bioavailability and ensuing endothelial dysfunction, may
      be proposed as a putative final common pathway afflicting the vascular
      endothelium in PLWHA. The HIV-1-proteins Tat, Gp120 and Nef in particular, the
      proinflammatory cytokine, TNF-alpha, and the antiretroviral drugs Efavirenz and
      Lopinavir, most commonly postulated to be primary causal agents of endothelial
      dysfunction, are also discussed. We conclude that, despite existing evidence from
      basic research papers, a significant gap remains in terms of the exact underlying
      cellular mechanisms involved in HIV-1 and ART induced endothelial dysfunction.
      Bridging this gap could help pave the way for future strategies to prevent and
      treat early cardiovascular changes in PLWHA.

PMID- 30220105
TI  - Preclinical studies reveal that LSD1 inhibition results in tumor growth arrest in
      lung adenocarcinoma independently of driver mutations.
AB  - Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung
      cancer. Despite the development of novel targeted and immune therapies, the 5
      year survival rate is still only 21%, indicating the need for more efficient
      treatment regimens. Lysine-specific demethylase 1 (LSD1) is an epigenetic eraser
      that modifies histone 3 methylation status, and is highly overexpressed in LUAD.
      Using representative human cell culture systems and two autochthonous transgenic
      mouse models, we investigated inhibition of LSD1 as a novel therapeutic option
      for treating LUAD. The reversible LSD1 inhibitor HCI-2509 significantly reduced
      cell growth with an IC50 of 0.3-5 MUmin vitro, which was linked to an enhancement
      of histone 3 lysine methylation. Most importantly, growth arrest, as well as
      inhibition of the invasion capacities, was independent of the underlying driver
      mutations. Subsequent expression profiling revealed that the cell cycle and
      replication machinery were prominently affected after LSD1 inhibition. In
      addition, our data provide evidence that LSD1 blockade significantly interferes
      with EGFR downstream signaling. Finally, our in vitro results were confirmed by
      preclinical therapeutic approaches, including the use of two autochthonous
      transgenic LUAD mouse models driven by either EGFR or KRAS mutations.
      Importantly, LSD1 inhibition resulted in significantly lower tumor formation and
      a strong reduction in tumor progression, which were independent of the underlying
      mutational background of the mouse models. Hence, our findings provide
      substantial evidence indicating that tumor growth of LUAD can be markedly
      decreased by HCI-2509 treatment, suggesting its use as a single agent maintenance
      therapy or combined therapeutical application in novel concerted drug approaches.

PMID- 30220107
TI  - Incidence of cardiovascular disease up to 13 year after cancer diagnosis: A
      matched cohort study among 32 757 cancer survivors.
AB  - We examined the incidence of cardiovascular disease (CVD) among 32 757 cancer
      survivors and age-, gender-, and geographically matched cancer-free controls
      during a follow-up period of 1-13 years, and explored whetherCVD incidence
      differed by received cancer treatment, traditional cardiovascular risk factors,
      age, or gender. Adult 1-year cancer survivors without a history ofCVD diagnosed
      with breast (n = 6762), prostate (n = 4504), non-Hodgkin (n = 1553), Hodgkin (n =
      173), lung and trachea (n = 2661), basal cell carcinoma (BCC; n = 12 476), and
      colorectal (n = 4628) cancer during 1999-2011 were selected from the Netherlands
      Cancer Registry and matched to cancer-free controls without a history ofCVD. Drug
      dispenses and hospitalizations from thePHARMO Database Network were used as proxy
      forCVD. Data were analyzed using Cox regression analyses. Prostate (HR: 1.17;
      95%CI: 1.01-1.35) and lung and trachea (HR: 1.48; 95%CI: 1.10-1.97) cancer
      survivors had an increased risk for developingCVD compared to cancer-free
      controls. This increased risk among lung and trachea cancer survivors remained
      statistically significant after including traditional cardiovascular risk factors
      and cancer treatment information (HR: 1.41; 95%CI: 1.06-1.89). Among prostate
      cancer survivors, the increased risk of incidentCVD was limited to those who
      received hormones and those without traditional cardiovascular risk factors.
      Breast, non-Hodgkin,BCC, and colorectal cancer survivors showed no increasedCVD
      risk compared to cancer-free controls. There was an increased risk of incidentCVD
      among prostate, and lung and trachea cancer survivors compared to age-, gender-
      and geographically matched cancer-free controls. Studies including longer follow
      up periods are warranted to examine whether cancer survivors are at increased
      risk of long-term incidentCVD.

PMID- 30220108
TI  - Resequencing core accessions of a pedigree identifies derivation of genomic
      segments and key agronomic trait loci during cotton improvement.
AB  - Upland cotton (Gossypium hirsutum) is the world's largest source of natural fibre
      and dominates the global textile industry. Hybrid cotton varieties exhibit strong
      heterosis that confers high fibre yields, yet the genome-wide effects of
      artificial selection that have influenced Upland cotton during its breeding
      history are poorly understood. Here, we resequenced Upland cotton genomes and
      constructed a variation map of an intact breeding pedigree comprising seven elite
      and 19 backbone parents. Compared to wild accessions, the 26 pedigree accessions
      underwent strong artificial selection during domestication that has resulted in
      reduced genetic diversity but stronger linkage disequilibrium and higher extents
      of selective sweeps. In contrast to the backbone parents, the elite parents have
      acquired significantly improved agronomic traits, with an especially pronounced
      increase in the lint percentage. Notably, identify by descent (IBD) tracking
      revealed that the elite parents inherited abundant beneficial trait segments and
      loci from the backbone parents and our combined analyses led to the
      identification of a core genomic segment which was inherited in the elite lines
      from the parents Zhong 7263 and Ejing 1 and that was strongly associated with
      lint percentage. Additionally, SNP correlation analysis of this core segment
      showed that a non-synonymous SNP (A-to-G) site in a gene encoding the cell wall
      associated receptor-like kinase 3 (GhWAKL3) protein was highly correlated with
      increased lint percentage. Our results substantially increase the valuable
      genomics resources available for future genetic and functional genomics studies
      of cotton and reveal insights that will facilitate yield increases in the
      molecular breeding of cotton.

PMID- 30220109
TI  - Quantitation of escitalopram and its metabolites by liquid chromatography-tandem
      mass spectrometry in psychiatric patients: New metabolic ratio establishment.
AB  - Therapeutic drug monitoring (TDM) is used to determine the concentration of drug
      in plasma/serum to adjust the dose of the therapeutic drug. Selective and
      sensitive analytical methods are used to determine drug and metabolite levels for
      the successful application of TDM. The aim of the study was to develop and
      validate using LC-MS/MS to analyse quantitative assay of escitalopram (S-CT) and
      metabolites in human plasma samples. In order to provide a convenient and safe
      treatment dose, it was aimed to determine the levels of S-CT and its metabolites
      in the patients' plasma. A new method with short sample preparation and analysis
      time was developed and validated using LC-MS/MS to analyse quantitative assay of
      S-CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20
      mg S-CT between the ages of 18 and 65 years were analysed by the validated
      method. The mean values of S-CT, demethyl escitalopram and didemethyl
      escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL,
      respectively. At the end of the analysis, the metabolic ratio of S-CT and
      metabolites was calculated. It is considered that the method for the quantitative
      analysis of S-CT and its metabolites in human plasma samples may contribute to
      the literature on account of its sensitive and easy application. Additionally,
      the use of our data by physicians will contribute to the effective drug treatment
      for their patients who take S-CT.

PMID- 30220110
TI  - Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid
      leukemia.
AB  - AML with the RAM immunophenotype is associated with extremely poor prognosis. We
      report a rare case of monozygotic twins presenting simultaneously at the age of 2
      years with RAM AML. Each twin underwent a myeloablative 7/10 unrelated umbilical
      cord blood transplant. Pretransplant Twin A's bone marrow was negative for MRD by
      flow cytometry (<0.01%) unlike Twin B's bone marrow (0.07%). Twin A is alive in
      remission 3 years from transplant. Twin B developed primary graft failure, but
      subsequently rescued with a haploidentical stem cell transplant. However, she
      relapsed and died 13 months from diagnosis. The twins' clinical courses
      demonstrate that upfront intensive chemotherapy to achieve negative MRD, followed
      by allogeneic hematopoietic stem cell transplant as postremission intensification
      strategy, should be considered in this high-risk AML.

PMID- 30220112
TI  - Associations among two vitamin D receptor (VDR) gene polymorphisms (ApaI and
      TaqI) in acne vulgaris: A pilot susceptibility study.
AB  - BACKGROUND: Acne vulgaris (AV) pathogenesis is multifactorial. Vitamin D (VitD)
      plays an important role in sebocytes' differentiation and function. Most VitD
      functions are mediated by the nuclear VitD receptor (VDR) following binding of
      its biologically active form (1,25 dihydroxyvitamin D3). Genetic variations in
      VDR gene may cause significant receptor dysfunction and have been found to be
      associated with many inflammatory skin diseases. Two adjacent single nucleotide
      polymorphisms of VDR, ApaI (rs7975232) and TaqI (rs731236), were commonly
      studied. OBJECTIVE: To evaluate the association between VDR ApaI and TaqI gene
      polymorphism and AV. METHODS: This case control study included 30 Egyptian acne
      patients who attended Dermatology Outpatient Clinic of Al-Zahraa University and
      Misr University for Science and Technology Hospitals. Thirty age- and sex-matched
      healthy individuals participated as controls. VDR gene ApaI and TaqI
      polymorphisms were examined by polymerase chain reaction restriction fragment
      length polymorphism. Serum 25(OH)D was measured in all participants. RESULTS:
      Patients had significant decrease in ApaI A allele and AATT combined genotype
      (60%, 3.3%) than controls (78.3%, 20%), respectively, and significant increase in
      TaqI tt genotype and t allele (46.7%, 63.3%) than controls (13.3%, 41.7%),
      respectively. Patients showed significantly lower serum 25(OH)D3 concentration
      than controls. CONCLUSION: Polymorphisms of ApaI and TaqI may have a role in the
      pathogenesis of AV as A allele and AATT combined genotype could be considered
      protective against acne development and tt genotype and t allele may increase the
      risk of AV development. VitD deficiency can be considered as a risk factor for AV
      development.

PMID- 30220113
TI  - Effect of synchronization protocols on reproductive indices, progesterone profile
      and fertility under subtropical environmental conditions in repeat breeder
      Holstein cows.
AB  - The objectives were to evaluate the reproductive indices and survival analysis of
      pregnancy outcomes in multiparous repeat breeder Holstein cows (n = 557). The
      cows were synchronized to ovulate by Ovsynch, new controlled internal drug
      release device (N-CIDRsynch), and once-used CIDR device (U-CIDRsynch). The
      pregnancy per AI at 28 days post-insemination (P/AI 28) in the N-CIDRsynch group
      (28.75%) was significantly (COR = 1.49; p = 0.011) greater than that reported in
      the Ovsynch (23.46%) and U-CIDRsynch (21.73%) groups. Furthermore, the pregnancy
      per AI at day 75 post-insemination (P/AI 75) in the N-CIDRsynch group was
      significantly greater than the Ovysync group (COR = 1.35; p = 0.050). The repeat
      breeder cows received a N-CIDR device had a significantly higher progesterone
      level on day 2 and day 4 of CIDR insertion (1.38 and 1.67 ng/ml, respectively)
      than those received a U-CIDR device or the control group (p = 0.012 and 0.001,
      respectively). The Cox regression model recorded significant associations for
      synchronization protocols, THI at the TAI and season of calving with the hazard
      of P/AI 28 and P/AI 75 (p = 0.044 and 0.046; 0.001 and 0.005; 0.003 and 0.001,
      respectively). Multiparous repeat breeder cows (>3) had a lower hazard ratio (HR)
      of P/AI 28 than that reported in the reference (2nd parity) group (HR = 0.74, p =
      0.050). The repeat breeder cows inseminated at 76-80 and >80 temperature-humidity
      index (THI) had significantly lower HR of P/AI 28 than those inseminated at the
      baseline (<70) THI value (HR = 0.73 and 0.30, p = 0.036 and 0.001, respectively).
      The current results indicate that the use of N-CIDR synch protocol may achieve
      satisfactory pregnancy outcomes in repeat breeder cows.

PMID- 30220111
TI  - Partially ablative radiotherapy (PAR) for large mass tumors using simultaneous
      integrated boost: A dose-escalation feasibility study.
AB  - PURPOSE: This study aimed to assess the feasibility to plan and deliver highly
      heterogeneous doses to symptomatic large tumors using volumetric modulated arc
      therapy (VMAT) and simultaneous integrated boost (SIB) during a short course
      palliative accelerated radiotherapy. METHODS: A patient with a large symptomatic
      chordoma infiltrating the right gluteal region was selected. A modified SIB
      treatment was implemented to irradiate the central volume of the tumor (boost
      target volume, BTV) up to 10 Gy/fraction in a dose escalation trial while
      maintaining the remaining tumor volume (planning target volume, PTV) and the
      surrounding healthy tissues within 5 Gy/fraction in twice daily fractions for two
      consecutive days. Four SIB plans were generated in the dual-arc modality; a basal
      dose of 20 Gy was prescribed to the PTV, while the BTV was boosted up to 40 Gy.
      For comparison purposes, plans obtained with a sequential boost (SEQ plans) were
      also generated. All plans were optimized to deliver at least 95% of the
      prescription dose to the targets. Dose contrast index (DCI), conformity index
      (CI), integral dose (ID), and the irradiated body volumes at 5, 10, and 20 Gy
      were evaluated. RESULTS: At equal targets coverage, SIB plans provided major
      improvement in DCI, CI, and ID with respect to SEQ plans. When BTV dose escalated
      up to 200% of PTV prescription, DCI resulted in 66% for SIB plans and 37% for SEQ
      plans; the ID increase was only 11% for SIB plans (vs 27% for SEQ plans) and the
      increase in healthy tissues receiving more than 5, 10, and 20 Gy was less than
      2%. Pretreatment dose verification reported a gamma-value passing rate greater
      than 95% with 3%(global)-2 mm. CONCLUSION: A modified SIB technique is
      dosimetrically feasible for large tumors, where doses higher than the tolerance
      dose of healthy tissues are necessary to increase the therapeutic gain.

PMID- 30220114
TI  - Content-oriented sparse representation (COSR) for CT denoising with preservation
      of texture and edge.
AB  - PURPOSE: Denoising has been a challenging research subject in medical imaging,
      since the suppression of noise conflicts with the preservation of texture and
      edges. To address this challenge, we develop a content-oriented sparse
      representation (COSR) method for denoising in computed tomography (CT). METHODS:
      An image is segmented into a number of content areas and each of them consists of
      similar material. Having been ex-painted, each content area is sparsely coded
      using the dictionary learnt from patches extracted from the corresponding content
      area. By constraining sparsity, noise is suppressed and the final image is formed
      by aggregating all denoised content areas. The performance of COSR method is
      examined with images simulated by computer and generated by multidetector row CT
      (MDCT), cone beam CT (CBCT), and micro-CT, in which water phantom,
      anthropomorphic phantom, a human subject, and a small animal are engaged, using
      the figures of merit, such as standard division (SD), contrast to noise ratio
      (CNR), and thresholded edge keeping index (EKIth ) and structural similarity
      index (SSIM). In addition, the optimization of performance by parameter tuning is
      also investigated. RESULTS: Quantitatively gauged by metrics of noise, EKIth and
      SSIM, the performance evaluation shows that the proposed COSR method is effective
      in denoising (>50% reduction in noise) while it outperforms the conventional
      sparse representation method in preservation of texture and edge by ~20% (gauged
      by SSIM). It has also been shown that the COSR method is tolerable to inaccuracy
      in content area segmentation and variation in dictionary learning. Moreover, the
      computational efficiency of COSR can be substantially improved using prelearnt
      dictionaries. CONCLUSIONS: The COSR method would find its utility in clinical and
      preclinical applications, such as low-dose CT, image segmentation, registration,
      and computer-aided diagnosis. The proposal of COSR denoising is of innovation and
      significance in the theory and practice of denoising in medical imaging. A
      demonstration code package is available at https://github.com/xiehq/COSR.

PMID- 30220115
TI  - Benign paroxysmal positional vertigo in children.
AB  - OBJECTIVE: To describe the clinical features of benign paroxysmal positional
      vertigo (BPPV) in children. DESIGN: A retrospective study. SETTING: Six children
      diagnosed with BPPV between March 2014 and March 2015 were retrospectively
      evaluated. BPPV was diagnosed using the Dix-Hallpike and supine roll tests and
      treated with either the modified Epley particle repositioning procedure or
      Lempert or Gufoni manoeuvre. Follow-up was performed at 1-week intervals until
      vertigo and nystagmus disappeared during positional testing. PARTICIPANTS: A
      total of six children were followed up for a period of 10-22 months. MAIN OUTCOME
      MEASURES: Clinical features such as history, nystagmus and symptoms of vertigo,
      dizziness and nausea. RESULTS: Six children were diagnosed with BPPV using
      positional testing and treated with the modified Epley or Lempert/Gufoni particle
      repositioning procedures. Four children were diagnosed with posterior canal BPPV,
      while the remaining two were diagnosed with horizontal canal BPPV. One girl
      reported a history of head trauma, one girl had a family history of vertigo, and
      one boy reported hearing loss in the same ear as that affected by BPPV. Overall,
      83.33% of children (5/6) were completely relieved of vertigo following one
      treatment session. The remaining child was asymptomatic after two sessions. No
      child reported relapse of vertigo during the follow-up period. CONCLUSIONS: BPPV
      can be diagnosed accurately by taking a detailed medical history and by use of
      positional testing. BPPV in children can be successfully identified and treated.

PMID- 30220116
TI  - The Cochrane Rehabilitation eBook: a knowledge translation tool to transfer
      evidence to different rehabilitation audiences.
AB  - Systematic reviews are a powerful method for summarizing and synthesizing
      evidence and create a methodological opportunity for preparing data integration
      tables to enable review-level synthesis of the evidence. One of the main tasks of
      Cochrane Rehabilitation is to make it possible to improve the application of
      evidence-based clinical practice by all rehabilitation professionals, and to
      facilitate policy-makers in decision-making according to the best evidence. In
      this context arises the need to diffuse the high-quality information of Cochrane
      Systematic Reviews (CSR), through synthetic and easy-to-use messages for the
      different rehabilitation audiences. Cochrane Rehabilitation has recently launched
      the production of an eBook including all the evidence coming from the CSR tagged
      by its Review Committee as of rehabilitation interest with the final aim to
      enhance the application of evidence in clinical practice, medical education,
      health system policies, and in the community. This will be a powerful tool for
      the dissemination of evidence-based practice, education and knowledge, as well as
      to support political decisions for both effective organization and resource
      allocation in rehabilitation field.

PMID- 30220117
TI  - [Prognostic significance of combined TERT and IDH gene mutation analysis in
      diffusely infiltrating gliomas].
AB  - Objective: To investigate the status and prognostic significance of TERT and
      IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot
      mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases
      of gliomas at West China Hospital from 2012 to 2016, including pilocytic
      astrocytoma (WHO grade I, 16 cases), diffuse astrocytoma and oligodendroglioma
      (WHO grade II, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade
      III, 72 cases) and glioblastoma (WHO grade IV, 59 cases). The prognostic
      significance of TERT and IDH1/2 hot spot mutations was evaluated. Results: No IDH
      or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation
      frequency was higher in patients aged >=40 years(60.8%, 93/153) than in patients
      aged <40 years (32.8%, 22/67; P<0.01). TERT promoter mutation rate was also
      significantly higher in oligodendroglioma (87.5% , 56/64) than that in
      astrocytoma(37.8%, 59/156; P<0.01). Young age (<40 years), oligodendroglioma and
      IDH1 mutation were favorable prognostic factors for diffusely infiltrating
      astrocytic and oligodendroglial tumors. TERT mutation alone was not of prognostic
      significance. Diffusely infiltrating astrocytic and oligodendroglial tumors were
      divided into four molecular subtypes according to TERT and IDH1 mutation status:
      IDH(+ )/TERT(+ ), IDH(+ )/TERT(-), IDH(-)/TERT(-) and IDH(-)/TERT(+ ). There was
      significant prognostic difference among the 4 subtypes. Conclusions: Combined IDH
      and TERT gene mutation analysis may be useful for prognostic subgrouping.
      Notably, IDH1 wild-type cases can be further subdivided into TERT(+ ) or (-)
      subgroups with significant prognostic difference.

PMID- 30220118
TI  - [BRAF V600E mutation and clinicopathologic characteristics in 250 cases of brain
      tumors associated with epilepsy].
AB  - Objective: To investigate the clinicopathologic characteristics and BRAF V600E
      mutation of brain tumors associated with epilepsy. Methods: Totally 250 patients
      with brain tumors associated with epilepsy were included from March 2008 to
      August 2017 retrospectively at Sanbo Brain Hospital, Capital Medical
      University.The clinical manifestations, histological features and BRAF V600E
      mutation results were collected and analyzed. Results: There were 132 males and
      118 females, and the male to female ratio was 1.1?1.0. The age of patients ranged
      from 2 to 67 years(mean 22 years). The tumors had obvious local space occupying
      effect on MRI. The temporal lobe was the most common site (44.4%, 111/250). There
      were 58.4% (146/250) of ganglioglioma (GG), 24.0% (60/250) of dysembryoplastic
      neuroepithelial tumor (DNT), 12.8% (32/250) of pleomorphic
      xanthoastrocytoma(PXA), 4.0% (10/250) of angiocentric glioma (AG) and 0.8%
      (2/250) of papillary glioneuronal tumor (PGNT). Mixed GG, PXA and DNT
      morphological structures were found in 9 of patients. Among 250 cases, 35 cases
      were accompanied by focal cortical dysplasia(FCD). BRAF V600E was seen in 43 of
      74 (58.1%) GG and 13 of 28 (46.4%) PXA. The most common pathologic grade of GG,
      DNT, AG and PGNT was WHO I. Some of the tumor cells from GG (34 cases) showed
      higher proliferative activity (WHO II/III). Most cases of PXA were WHOIIand high
      proliferative activity was seen in nine cases. Conclusions: The association of
      low-grade glioneuronal tumors with intractable epilepsy was well-recognized. The
      most common low-grade glioneuronal tumors were GG.GG may occur in any part of the
      central nervous system, with a predilection for temporal lobe. Each type of low
      grade glioneuronal tumors has its own unique histological morphology, but some
      may show complex features with 2 or 3 mixed components. The occurrence of BRAF
      V600E mutations in GG is common, and their detection may be valuable for the
      diagnosis and treatment in GG.

PMID- 30220119
TI  - [Neuropathologic study of massive subcortical heterotopia].
AB  - Objective: To investigate the clinicpathologic features and probable mechanisms
      of massive subcortical heterotopia. Methods: Clinical data, histologic features
      and neuropathologic data were analyzed in five cases of massive subcortical
      heterotopia collected from Xuanwu Hospital, Capital Medical University from
      January 2014 to October 2017. Results: All five patients (three males and two
      females) had a history of refractory epilepsy with a mean period of 15.4 years
      (range 7 to 21 years). The median age at surgery was 28.6 years(range 20 to 39
      years). Magnetic resonance imaging showed that the lesions were located in the
      temporal lobe (two cases), parietal lobe (one case), both temporal and occipital
      lobes (one case) and both temporal and parietal lobes (one case). Pathologic
      examination disclosed that massive gray matter in subcortical and deep white
      matter with various shape and size. Moreover, one case also showed subpial and
      periventricular heterotopias and polymicrogyria. Polymicrogyria or hippocampal
      sclerosis were seen in the remaining three cases. None of the five patients
      experienced seizure attacks during the follow-up period. Conclusions: Heterotopia
      is malformations due to abnormal neuronal migration. Massive subcortical
      heterotopia due to widespread abnormal neuronal migration is relatively rare. The
      mechanism of heterotopia together with polymicrogyria needs further discussion.

PMID- 30220120
TI  - [Rasmussen syndrome: a clinicopathologic study of four cases].
AB  - Objective: To investigate the clinicopathologic features of Rasmussen syndrome
      (RS) and to raise awareness of this rare disease. Methods: Clinicopathologic data
      of 4 cases of RS were retrospectively analyzed at Beijing Haidian Hospital from
      2008 to 2016. Results: The clinical manifestations included epilepsia partialis
      continua and progressive neurologic deficits in all patients.MRI demonstrated
      unihemispheric focal cortical atrophy in all cases. The histopathologic changes
      included variable degrees of lymphocytic infiltrate within the cortex,
      subarachnoid space and perivascular cuffing.Microglial nodules and neuronophagia
      were seen. Mild to severe neuronal loss was noted with variable degrees of
      reactive gliosis. Spongy edema and cavitation were observed in focal cortex.
      Inflammation involving hippocampus was seen in one case. Three cases were
      accompanied by focal cortical dysplasia (FCD) IIId. Immunohistochemical staining
      showed that the infiltrative lymphocytes were positive for CD3, CD8, granzyme B
      and TIA1 and the proliferating microglial cells were positive for CD68. NeuN
      positive neurons decreased significantly and reactive astrocytes were GFAP
      positive. Conclusions: Pathologic changes of RS are similar to viral encephalitis
      and the inflammation is progressive and multifocal involving the hemisphere. The
      diagnosis of RS relies on pathologic features combined with clinical findings and
      neuroradiological examinations.

PMID- 30220121
TI  - [Significance of HPV and cell cycle related proteins in basaloid squamous cell
      carcinoma of the larynx].
AB  - Objective: To study the significance of HPV and cell cycle related proteins in
      basaloid squamous cell carcinoma (BSCC) of the larynx. Methods: Twenty-nine cases
      of laryngeal BSCC from Beijing Tongren Hospital from January 2005 to December
      2011 were reviewed. HPV typing by polymerase chain reaction-reverse dot blot (PCR
      RDB) and p53, Ki-67, p16, p21 and cyclin D1 expression by immunohistochemistry
      were performed. The relationship between these indicators, various pathologic
      parameters (TNM, tumor size, tumor site and lymph node metastasis) and HPV status
      was analyzed. Results: There were 27 male and 2 female patients. The median age
      was 62 years. Lymph node metastasis and supraglottic tumor location were slightly
      higher than that of "usual" SCC, but not statistically significant (P>0.05). HPV
      DNA was detected in 27.6% (8/29) of the laryngeal BSCC, and all were HPV16. The
      expression of HPV was not related to age, alcohol consumption, tumor stage and
      tumor size. p53 was expressed in 31.0%(9/29) of laryngeal BSCC, and these cases
      were more likely supraglottic and had lymph node metastases (P<0.05). p16
      staining was seen in 24.1% (7/29) of laryngeal BSCC, and these cases showed
      slightly higher rate of lymph node metastasis compared to p16 negative cases. The
      expression rates of p21 and cyclinD1 were 27.6% (8/29) and 69.0%(20/29),
      respectively, which were not related to age, tumor size, stage, lymph node
      metastasis, smoking and drinking. There were only 3 p16+ /HPV+ cases, which
      showed higher p21 and Ki-67 index compared to the HPV negative group (P<0.05).
      Conclusion: Some laryngeal BSCC expresses HPV DNA, possibly indicating an
      association with HPV; but p16 expression is not a reliable indicator for HPV
      infection.

PMID- 30220123
TI  - [Clinicopathologic features and prognosis of adenoid cystic carcinoma of external
      auditory meatus].
AB  - Objective: To investigate clinicopathologic features and prognosis of adenoid
      cystic carcinoma (ACC) involving external auditory meatus. Methods: The clinical
      presentation and follow-up data of 63 patients with ACC of external auditory
      canal were collected from January 2006 to February 2017 at PLA General Hospital
      and Hainan Branch of PLA General Hospital. The clinicopathologic features and
      prognostic factors of external auditory canal ACC were analyzed. Results: (1)
      There were 28 males and 35 females and the average age of the first diagnosis was
      48.9 years (22-81 years). The tumors showed cribriform pattern in 35 cases (15
      cases of late stage), tubular pattern in 14 cases (8 cases of late stage), and
      solid pattern in 14 cases (9 cases of late stage). Cases with solid pattern was
      relatively more frequent than that of cribriform pattern and tubular pattern, but
      the difference was not statistically significant (P>0.05). (2) The average follow
      up time was 62.4 months (2-228 months) in the 57 available cases. Among the 33
      cases with recurrence, 18 cases had local recurrence and 15 cases had distant
      metastasis. The mean recurrence time was 40.6 months (2-204 months). Nine
      patients died of ACC: 2 cases in early stage (died at 48 and 102 months after the
      first treatment), 7 cases in late stage and 57 with (died at 9, 30, 32, 60, 72,
      94 and 228 months). (3) Among the 37 patients with perineural invasion, there
      were 21 cases of cribriform pattern, 4 cases of tubular pattern and 12 cases of
      solid pattern; the number of cases in early stage and late stage were 15 and 22,
      respectively; and the differences were statistically significant (P<0.05). In
      addition, 31 cases had otalgia among the 37 patients with perineural invasion,
      where differences were not significant (P>0.05). (4) Thirty of 45 cases with
      tumor resection or partial resection of temporal bone had recurrence, whereas 3
      of 12 cases of tumor combined with superficial lobectomy of parotid gland had
      recurrence. The difference was statistically significant (P<0.05). Postoperative
      adjuvant radiotherapy was given in 19 cases, including 7 cases of early stage (2
      cases of recurrence), and 12 cases of late stage (8 cases of recurrence), among
      which there was no significant difference (P>0.05). Conclusions: ACC occurring in
      external auditory canal frequently recurs. Superficial parotid lobectomy at the
      first operation is necessary to prevent tumor recurrence. Postoperative adjuvant
      radiotherapy has certain curative effect on patients with early stage tumor, but
      it does not affect the recurrence rate. Patients at late stage are more prone to
      perineural invasion than those in early stage. In addition, cribriform and solid
      patterns are more common that tubular pattern, and there is no significant
      correlation between perineural invasion and otalgia.

PMID- 30220122
TI  - [KRAS mutations analysis in mucinous epithelial lesions of the endometrium].
AB  - Objective: To investigate the frequency of KRAS mutation in mucinous epithelial
      lesions of the endometrium, and analyze the correlation between KRAS mutation and
      the clinicopathologic features. Methods: The cohort included forty-three cases of
      mucinous epithelial lesions of the endometrium selected from July 2015 to October
      2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases.
      Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections.
      Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed,
      followed by sequencing using capillary electrophoresis. The Fisher exact test was
      used to compare the prevalence of KRAS mutation among the different groups.
      Results: The patients'age ranged from 33 to 77 years [mean (55.12+/-9.34) years,
      median 55 years]. None of the eight cases of endometrial hyperplasia with
      mucinous differentiation without atypia showed KRAS mutation. The frequency of
      KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid
      carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation
      (EAHMD), 6/15 in endometrioid carcinoma with mucinous differentiation (ECMD) and
      8/9 in mucinous carcinoma (MC), respectively. The differences were statistically
      significant between MC versus EC (P<0.01) and MC versus ECMD (P<0.05).
      Conclusion: The high frequency of KRAS mutation in EAHMD, ECMD and MC indicates
      that KRAS mutational activation is implicated in the pathogenesis of endometrial
      mucinous carcinoma.

PMID- 30220124
TI  - [Cut-off value of Ki-67 labeling index in the pathologic grading of follicular
      lymphoma].
AB  - Objective: To determine the cut-off values of Ki-67 labeling index (LI) in the
      histological grading of follicular lymphoma (FL). Methods: Clinicopathological
      data of 350 FL patients diagnosed at Beijing Friendship Hospital from June 2014
      to January 2016 were analyzed retrospectively by quantitative evaluation and
      statistical analysis of Ki-67 LI. Results: Of the 350 patients with FL, the male
      and female ratio was 1.1 and the average age was (50.2+/-14.0) years with a
      median age of 51 years (range 4 to 82 years). The tumors were graded as grade I
      II in 215 cases (61.4%), grade III A in 105 cases (30.0%), and grade III B in 30
      cases (8.6%). The average Ki-67 values were (22.8%+/-8.3%) for the FL low (grade
      I-II) and (50.4%+/-10.7%) for high grade (III A and III B) and were statistically
      significant by Mann Whitney U test (P<0.01). Receiver operated characteristic
      curve analysis showed that the best diagnostic cut-off value of low grade FL was
      35% (sensitivity of 96.3% and specificity of 93.3%) with the largest area under
      curve (AUC=0.990, P<0.01, 95%CI for 0.982-0.998). According to the analysis of
      four lattice diagnostic tests, Ki-67 LI >40% was an important factor
      (chi2=230.733, P<0.01) in predicting high grade FL. When the cut-off value of Ki
      67 LI was set at 40%, high grade LF could be diagnosed with the greatest
      sensitivity (98.1%) and specificity (87.7%). Moreover, a significant correlation
      between the Ki-67 LI and the pathological grade of FL (r=0.836, P<0.01) was
      observed. Conclusions: Ki-67 LI of below a cut-off value of 35% is a reliable
      indicator of low grade FL.Ki-67 over 40% is consistent with high grade FL. These
      Ki-67 cut-off values may serveas an important auxiliary indicator in the grading
      of FL.

PMID- 30220125
TI  - [Myxoid variant of angiomatoid fibrous histiocytoma: a clinicopathologic analysis
      of 3 cases].
AB  - Objective: To study clinicopathologic features, diagnosis and differential
      diagnosis of myxoid variant of angiomatoid fibrous histiocytoma (AFH). Methods:
      Three cases of myxoid variant of AFHs were collected from First Affiliated
      Hospital of Nanjing Medical University during 2008 and 2017. EnVision method and
      fluorescence in situ hybridization(FISH) were used to detect immunophenotype and
      EWSR1 gene rearrangement, respectively. Results: There were 2 males and l female
      with age at 13, 31, and 42 years, respectively. The patients presented with a
      painless mass located superficially (subcutaneous or submucosal) in two cases or
      deep-seated (retroperitoneum) in one case. Grossly, the diameters of tumors were
      1, 7, and 2 cm, respectively. The cut surface was solid and firm, tan to gray in
      colour. Histologically, the circumscribed tumor had fibrous pseudocapsule and
      peritumoal lymphoplasmacytic infiltrates. The tumor cells arranged in vaguely
      nodular growth pattern, with prominent myxoid stroma (present in 60% to 100% of
      the entire tumor). In hypocellular myxoid areas, the spindle to stellate tumor
      cells arranged in cords or reticular pattern, or in a haphazard manner. However,
      histiocytoid cells arranged in fascicular, sheet-like, or whorled growth pattern,
      as in classical AFH, were also identified in hypercelluar areas. Mild to moderate
      atypia was observed with low mitotic rate of (0-2)/10 HPF. Tumor necrosis was not
      seen. One case presented with slit-like hemorrhage and sclerosing collagen
      intermingled with myxoid matrix was identified in 1 case. Immunohistochemically,
      all cases were positive for CD68 and CD163. Two of three were positive for
      desmin, EMA, CD99 and one for Calponin, SMA. All cases were negative for S-100
      protein, CD34, CD31, CD35, CD21 and CKpan. FISH detection was positive for EWSRl
      gene in all cases. Available clinical follow-up was obtained in 2 cases,
      revealing no evidence of disease in 6 and 89 months, respectively. Conclusions:
      Myxoid variant of AFH is a histological subtype of AFH, with clinical features,
      immunophenotypes, genomic profiles and biological behavior similar to typical
      AFH. Their unusual morphology is easily confused with a variety of other myxoid
      mesenchymal neoplasms, including myoepithelioma and nerve sheath tumors.

PMID- 30220126
TI  - [Chest wall hamartoma of infancy: a clinicopathologic observation of five cases].
AB  - Objective: To study the clinicopathologic features, diagnosis and differential
      diagnosis of chest wall hamartoma of infancy. Methods: The clinical data,
      histopathologic features and immunophenotype of five chest wall hamartomas were
      analyzed, and the relevant literature was reviewed. Results: The patients' age
      ranged from seven months and eight days to 20 months at time of resection,
      although the lesions were detected in the neonatal period. The male-to-female
      ratio was 4?1. Three cases were unilateral, two presented with multiple lesions;
      and four were located on the right side. CT-scan of the chest showed expansile
      soft tissue masses with heterogeneous density containing calcifications or
      ossifications in one or more ribs showing partial bone destruction. Patients were
      all treated by complete resection. Grossly, the lesions comprised solid and
      cystic areas, the latter showing hemorrhage. Microscopic examination revealed the
      solid areas were composed of islands of multilobulated hyaline cartilage
      interspersed within spindle or oval mesenchymal cells, waved bone and collagen
      fibers. Around the chondroid tissue, there were focal endochondral ossification
      and mucus-like background. In addition, there were areas of aneurysmal bone cyst
      like changes formed by hemorrhagic dilated cystic spaces. Immunohistochemistry
      was generally not necessary to establish the diagnosis. Conclusions: Chest wall
      hamartoma is a rare but benign lesion of infancy, showing characteristic
      clinicopathologic features. The prognosis are excellent after complete surgical
      excision.

PMID- 30220127
TI  - [Visceral parasitic migration of liver: a clinicopathologic analysis of seven
      cases].
AB  - Objective: To investigate the clinical, radiological and pathological features of
      visceral parasitic migration of the liver. Methods: Seven cases of visceral
      parasitic migration of liver were identified at the Affiliated Drum Tower
      Hospital of Medical School of Nanjing University from January 2008 to July 2017.
      Clinical data, enhanced CT image and pathological features were analyzed,
      combining with literature review. Results: There were 5 male and 2 female
      patients. Five patients presented with abdominal pain or discomfort as the first
      symptom. Two patients were admitted to the hospital for physical examination with
      liver nodule. Blood eosinophils were mildly to moderately increased in 4 cases.
      Enhanced CT showed the liver irregular beaded nodules that showed no significant
      enhancement of arterial phase. Mild enhancement of round lesions (ring lesion)
      was seen in a few cases before surgery. By histopathology, the lesions showed
      central geographic necrosis, surrounded by epithelioid granuloma and inflammatory
      cell bands. A large number of eosinophils and scattered multinucleated giant
      cells were found, especially at the peripheral of the lesion. Charcot-Leyden
      crystals were present in all case and parasitic migrans was found in one case.
      Conclusions: Visceral parasitic migration of liver is a rare liver disease and is
      easily misdiagnosed as other benign or malignant liver tumors. Combining clinical
      data, enhanced CT images and pathological examination can improve the
      preoperative and postoperative diagnosis of the disease.

PMID- 30220129
TI  - [Basaloid squamous cell carcinoma of the cervix with adenoid cystic cancer
      features: a clinicopathologic analysis of 3 cases].

PMID- 30220128
TI  - [Expression of protein phosphatase 2AC in the brain of mice and Alzheimer's
      patients].
AB  - Objective: To investigate the biological functions of protein phosphatase
      2AC(PP2AC) in the brain, and to detect its spatio-temporal expression and its
      involvement in neurological disorders in the brains of mice and Alzheimer's
      patients. Methods: Western blot was used to evaluate the expression level of
      PP2AC in different organs. Immunohistochemical staining was performed to detect
      the in situ expression levels of PP2AC in the brains of mice and patients, and
      the pathological changes were confirmed in the brains of patients with
      Alzheimer's disease. Results: Among all the tested organs in adult mouse, the
      expression of PP2AC protein was the highest in the brain. From embryonic day 18.5
      to postnatal 2-year-old mice, PP2AC exhibited spatio-temporal specific expression
      in the brains. Furthermore, an age-dependent increased expression in the cerebral
      cortex at both protein and RNA levels was observed. Compared to control group,
      PP2AC protein expression was lower in the frontal cortex of Alzheimer's patients.
      Conclusions: The spatio-temporal specific expression profiles of PP2AC in mouse
      brain implicate its biological significance. Its diminished expression in the
      frontal cortex of Alzheimer's disease patients implies that PP2AC plays a
      potential role in the pathogenesis of Alzheimer's disease.

PMID- 30220130
TI  - [MiR--210 promotes 5--fluorouracil resistance in breast cancer cells by
      increasing the antioxidant activity mediated by GPX1].

PMID- 30220131
TI  - [Modified colloidal iron combination method reveals cryptococcus neoformans in
      human lung tissue].

PMID- 30220132
TI  - [Sister Mary Joseph nodules: report of a case].

PMID- 30220133
TI  - [Inflammatory myofibroblastic tumor of the uterus: report of a case].

PMID- 30220134
TI  - [The interpretation of the Bethesda system for reporting thyroid cytopathology in
      2018].

PMID- 30220135
TI  - [Clinicopathological features and diagnostic approach of struma ovarii].

PMID- 30220136
TI  - [The role and molecular mechanism of autophagy in the development of prostate
      cancer].

PMID- 30220137
TI  - [Research progress of urethral repair after prostatectomy].

PMID- 30220138
TI  - [Activation of HIF-1alpha/beta-catenin signal pathway leads to radioresistance of
      prostate cancer cells].
AB  - Objective: To investigate the role of hypoxia-inducible factor-1alpha (HIF
      1alpha) and beta-catenin in radioresistance of prostate cancer (PCa) cells.
      Method: Two PCa cell lines, LNCaP and C4-2B, were grouped as: negative control
      (no treatment), HIF-1alpha overexpression group (transfected with HIF-1alpha
      plasmids), and beta-catenin silencing group (transfected with HIF-1alpha plasmids
      and beta-catenin-shRNA). Cell proliferation, cycle, invasion, and
      radiosensitivity were measured under normal or hypoxic condition.
      Radiosensitivity was tested in two mice PCa models (the LNCaP orthotopic BALB/c
      nu mice model and the C4-2B subcutaneous SCID mice model). Results: In both LNCaP
      and C4-2B cells, HIF-1alpha transfection led to an enhanced beta-catenin nuclear
      translocation, while beta-catenin silencing inhibited the beta-catenin nuclear
      translocation. Enhanced beta-catenin nuclear translocation caused by HIF-1alpha
      overexpression resulted in enhanced cell proliferation and invasion, altered cell
      cycle distribution, reduced apoptosis, and improved non-homologous-end-joining
      (NHEJ) repair under irradiation condition. In vivo imaging of orthotopic models
      showed that HIF-1alpha overexpression LNCaP cells produced tumors with 3-fold
      volume (P=0.003 1) and 2-fold wet weight (P=0.039 4) than those by negative
      control cells at day 21, and beta-catenin silencing cells aberrantly reduced both
      tumor volume (P=0.000 3) and wet weight (P=0.017 5) than HIF-1alpha
      overexpression cells. In addition, C4-2B subcutaneous models showed similar tumor
      promotion effects induced by HIF-1alpha overexpression (tumor volume: P=0.000 1
      and wet weight: P=0.047 3) and suppressive effects by beta-catenin silencing
      (tumor volume: P<0.000 1 and wet weight: P=0.022 1) as LNCaP orthotopic xenograft
      with regard to tumor volume and wet weight. Conclusions: HIF-1alpha
      overexpression enhanced beta-catenin nuclear translocation, which led to the
      activation of the beta-catenin/NHEJ signaling pathway and increased cell
      proliferation, invasion, and DNA repair. These results suggest that HIF-1alpha
      overexpression led to radioresistance of PCa cells.

PMID- 30220139
TI  - [Developing a Chinese PI-RADS v2-based nomogram for predicting clinically
      significant prostate cancer in patients with a prior negative biopsy].
AB  - Objective: To develop a nomogram based on prostate imaging reporting and data
      system version 2 (PI-RADS v2) to predict clinically significant prostate cancer
      in patients with a prior negative prostate biopsy. Methods: The clinical and
      pathological data of 231 patients who underwent repeat prostate biopsy and
      multiparametric MRI (mpMRI) were reviewed. Based on PI-RADS v2, the mpMRI results
      were assigned as PI-RADS grade from 0 to 2. A Logistic regression nomogram for
      predicting the probabilities of clinically significant prostate cancer were
      constructed. The performances of the nomogram were assessed using area under the
      receiver operating characteristic (ROC) curve, calibrations and decision curve
      analysis. Results: Of the total 231 repeat prostate biopsy patients, clinically
      significant prostate cancer was detected in 59 cases(25.5%). In multivariate
      Logistic regression analysis, age, prostate specific antigen (PSA), prostate
      volume (PV), digital rectal examination (DRE) and mpMRI results were significant
      independent predictors of the diagnosis of clinically significant prostate cancer
      (P<0.05). The nomogram with super predictive accuracy were constructed
      (AUC=0.927, P<0.001), and exhibited excellent calibration. Decision curve
      analysis also demonstrated a high net benefit across a wide range of threshold
      probabilities . Conclusions: PI-RADS v2 combined with age, PSA, PV and DRE can
      predict the probability of clinically significant prostate cancer in patients
      with negative initial biopsies. The nomogram generated may help the decision
      making process in patients with prior benign histology before the performance of
      repeat biopsy.

PMID- 30220140
TI  - [Effect of HCO3- level on the accuracy of NoSAS screening for obstructive sleep
      apnea hypopnea syndrome].
AB  - Objective: To evaluate the effect of arterial blood HCO3- level on the accuracy
      of NoSAS questionnaire screening for obstructive sleep apnea hypopnea syndrome
      (OSAHS). Methods: The hospitalized patients with suspected OSAHS were recruited
      from March 2016 to December 2017 in the First Affiliated Hospital of Guangzhou
      Medical University. NoSAS scores, blood gas analysis and polysomnography (PSG)
      were performed in these patients. Patients were divided into non OSAHS group and
      mild, moderate and severe OSAHS group according to the PSG results. According to
      the NoSAS questionnaire score, the patients were divided into OSAHS high-risk
      group and low risk group. The correlation between arterial blood HCO3- level and
      apnea hypopnea index (AHI) was analyzed. The receiver operating characteristic
      (ROC) curve was plotted to analyze the accuracy of HCO3- prediction OSAHS.
      Predictive parameters(sensitivity, specificity, positive and negative predictive
      values)for NoSAS scores and HCO3- level were calculated. Results: A total of 243
      patients with suspected OSAHS were included, including 186 males (76.5%), 57
      females (23.5%), age (49+/-13) years, body mass index (BMI) (26.9+/-4.4) kg/m2,
      and neck circumference (38.6+/-4.5) cm. The HCO3- level was positively correlated
      with AHI (r=0.206, P=0.001). The proportion of patients with HCO3- level >=26
      mmol/L in non-OSAHS group was lower than that in OSAHS group (13.0% vs 34.5%,
      P=0.004); the proportion of patients with HCO3- level >=26 mmol/L in severe OSAHS
      group was higher than that in mild OSAHS group (37.7% vs 15.0%, P=0.008), and
      there was no difference in the ratio of patients with severe OSAHS and moderate
      OSAHS (37.7% vs 35.3%, P=0.767). The specificity of OSAHS predicted by HCO3-
      level 25 and 26 mmol/L was 69.6% and 87.0%, respectively. With the NoSAS score of
      8 or 7 as cutoffs for analysis, the sensitivity for OSAHS was 61.9% and 79.2%,
      the specificity for OSAHS was 57.4% and 40.4%, respectively. With the addition of
      HCO3- level >= 26 mmol/L to the NoSAS score >= 7, the specificity for OSAHS
      improved to 93.6%, while the sensitivity decreased to 27.4%. Conclusion: Combined
      with the arterial blood HCO3- level, the specificity of the NoSAS questionnaire
      increases and the sensitivity decreases.

PMID- 30220141
TI  - [The influence of Thymidine Phosphorylase genetic variation on clinical outcomes
      and safety of colorectal cancer patients received adjuvant chemotherapy after R0
      resection].
AB  - Objective: To study the association between Thymidine Phosphorylase (TYMP)
      genetic variation and clinical outcomes and safety of postoperative colorectal
      cancer (CRC) patients. Methods: A total of 235 patients with colorectal cancer
      underwent surgical treatment were included in this retrospective analysis.
      Peripheral blood and the postoperative tissue specimen of the CRC patients were
      collected for the genotyping of polymorphism and TYMP mRNA expression,
      respectively. The correlation between polymorphism and clinical outcomes and
      safety of postoperative CRC patients were analysed. Results: Located in the
      upstream, 5633C>T was of clinical significance. The prevalence of 5633C>T in TYMP
      among the CRC patients were as follows: CC genotype 149 cases (63.40%), CT
      genotype 73 cases (31.06%), TT genotype 13 cases (5.54%), minor allele frequency
      of 5633C>T is 0.21. The distribution of three genotypes was in accordance with
      Hardy-Weinberg Equilibrium (P=0.313). CT genotype and TT genotype patients were
      merged in the comparison of prognosis. The survival analysis of patients with
      different genotypes found that the median Overall Survival (OS) of CT/TT genotype
      and CC genotype were 5.8 and 4.5 year, which was statistically significant
      (P=0.009). Adjusted in multivariate Cox regression analysis, CT/TT genotype was
      an independent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the
      87 postoperative tissue specimens, the results showed that the expression of TYMP
      in cancer tissues of the patients with CT or TT genotypes were significantly
      higher than those of the wild type CC genotype patients (P=0.019). And the safety
      analysis showed that the incidence of grade 3 hand-foot syndrome among CT/TT
      genotype patients were higher than that of CC genotype patients (33.72% vs
      20.13%, OR=1.68, P=0.021). Conclusion: The polymorphism 5633C>T of TYMP may
      impact the prognosis of CRC patients received adjuvant chemotherapy by
      influencing the mRNA expression of TYMP.

PMID- 30220143
TI  - [Clinical high risk factors and prognosis of 25 pulmonary mucormycosis cases].
AB  - Objective: To analyze high risk factors, therapeutic regimen and prognosis of
      patients with pulmonary mucormycosis. Methods: A retrospective analysis was
      performed on the clinical data of 25 patients who were diagnosed as pulmonary
      mucormycosis in the First Affiliated Hospital, School of Medicine, Zhejiang
      University, between January 2009 and December 2017. Results: Univariate analysis
      revealed that no risk factor had significant effect on prognosis of these 25
      cases, while multivariate logistic regression analysis confirmed that the
      exposure to antifungal drugs was correlated to worse prognosis(P=0.046). All 4
      patients who had received surgical lesionectomy were cured, and 8 patients who
      had not received any therapy targeted to mucormycosis were all dead. Seven of 13
      patients received antifungal drug to mucormycosis were effective, with an
      effective rate of 54.0%. The mortality rate of the operative group was lower than
      that of the non-operative group (P=0.026), and the prognosis of the patients
      received drug treatment was better than patients without treatment(P=0.022).
      There was no significant difference in the prognosis between groups of single
      drug or combination of amphotericin B and posaconazole. Conclusions: Pulmonary
      mucormycosis is more likely to occur in patients with tumor of the hematopoietic
      and lymphoid tissues, immunosuppression after solid organ transplantation, long
      term glucocorticoid usage and diabetes. Surgical lesionectomy can improve the
      survival rate, and the treatment with amphotericin B and /or posaconazole can
      also improve the prognosis of the patients.

PMID- 30220142
TI  - [Impact of first-line chemotherapy on renal function in patients with advanced
      upper tract urothelial carcinoma].
AB  - Objective: To observe the impact of first-line chemotherapy on renal function in
      patients with unresectable/metastatic upper tract urothelial carcinoma(UTUC).
      Methods: A total of 222 (130 males and 92 females) unresectable/metastatic upper
      tract urothelial carcinoma patients were included in the study between January
      2005 and May 2017, with age of 29 to 87 (62.4+/-10.1) years old. The serum
      creatinine level and estimated glomerular filtration rate (eGFR) were compared
      before and after first-line chemotherapy. And predictive factors for decreased
      renal function were analyzed in logistic regression model. Results: After the
      first-line chemotherapy, the average serum creatinine level increased, with a
      median changing value of 1.5 MUmol/L. Howerver, the eGFR improved, with a median
      changing value of 0.5 ml.min-1. (1.73 m2)-1, but the differences were not
      statistically significant (all P>0.05). In 149 patients who were treated with
      cisplatin-based chemotherapy, the average serum creatinine level increased by
      1.31 MUmol/L and eGFR improved by 0.14 ml.min-1.(1.73 m2)-1, but the differences
      were not statistically significant (P>0.05). In multivariate logistic regression
      model, age more than and equal to 60 years old (OR=0.88, P=0.745) and cisplatin
      based chemotherapy (OR=0.95, P=0.893) did not increase the risk of renal
      dysfunction after first-line chemotherapy. If the time interval between surgery
      and first-line chemotherapy was more than 1 year, the risk of renal dysfunction
      due to chemotherapy decreased (OR=0.54, P=0.196). Eastern Cooperative Oncology
      Group Performance Status (ECOG PS) Scale>=1 (OR=1.81, P=0.131), anemia before
      treatment (OR=1.14, P=0.764), the cycles of first-line chemotherapy (OR=1.41,
      P=0.398) may lead to increase the risk of renal dysfunction, but the differences
      were not statistically significant. However in the patients who accepted
      nephrectomy, the risk of renal dysfunction after chemotherapy increased, but the
      difference was still not statistically significant (OR=3.06, P=0.089).
      Conclusions: First-line chemotherapy, especially the cisplatin-based regimen, had
      no significant impact on renal function in the patients with UTUC. Nephrectomy
      maybe a predictive risk factor for decreased renal function after chemotherapy.
      Adequate assessment of renal function before treatment, hydration and close
      monitoring during chemotherapy can effectively protect renal function of the
      patients.

PMID- 30220144
TI  - [Clinical significance of the ratio of serum beta-CTX/PINP in multiple myeloma
      bone diseases and bone metastases].
AB  - Objective: To explore the clinical significance of serum bone metabolites beta C
      termianl telopeptide of type I collagen(beta-CTX), Procollagen type I N-terminal
      peptide(PINP) concentration and ratio of beta -CTX/PINP in multiple myeloma bone
      disease (MMBD) and bone metastases. Methods: A total of 31 cases of MM, 46 cases
      of bone metastases and 12 healthy controls were enrolled in the department of
      hematology, oncology and physical examination center of Henan Provincial People's
      Hospital respectively from October 2016 to October 2017. According to the imaging
      findings, MMBD was divided into 0-4 grades, group A included the patitents with
      grade 0-2 of osteopathy (n=8), and group B included the grade 3-4 (n=23). After
      two courses of chemotherapy, the curative effect was evaluated. MM group were
      divided into effective group (above partial remission , n=22) and uneffective
      group (unreached partial remission, n=9). ELISA method was used to detect the
      concentration of serum beta -CTX and PINP, and the ratio of beta -CTX/PINP was
      calculated. Results: The serum beta -CTX concentration in newly diagnosed MM,
      bone metastases and healthy control were (3 563 +/- 544)ng/L, (6 690+/-343)ng/L,
      (2 726+/-1 026)ng/L (chi2=22.207, P<0.001), PINP concentration were (72 +/- 14)
      ng/L, (112 +/- 62) ng/L, (171 +/- 62) ng/L (chi2=7.418, P=0.024) , and beta 
      CTX/PINP ratio were 93+/-19, 141+/-21, 17+/-8 (chi2=20.192, P<0.001), the
      differences were statistically significant. The ratio of initial MM beta 
      CTX/PINP was higher than that of healthy control (P=0.001). The concentration of
      beta -CTX (P=0.003) and the ratio of beta -CTX/PINP(P<0.001) in bone metastases
      were higher than those in healthy controls. The serum concentration of beta-CTX
      in newly diagnosed MM was lower than that in bone metastases (P<0.001). Before
      chemotherapy, the serum levels of beta -CTX and PINP in A and B groups were not
      statistically significant, but the ratio of serum beta -CTX/PINP in A group was
      lower than that in group B, and the difference was statistically significant.
      After two courses chemotherapy, the concentration of serum beta -CTX (P=0.023)
      and the ratio of beta -CTX/PINP (P<0.001) were decreased in MM group. There were
      no significant difference of serum beta -CTX, PINP concentration, and beta
      CTX/PINP ratio before and after treatment in Group A. Patients in the group B,
      there was no significant difference in the changes of serum PINP concentration,
      but both serum beta -CTX concentration and beta-CTX/PINP ratio decreased after
      two courses[(4 027 +/- 648)ng/L vs (2 370+/- 460) ng/L, P=0.043; 111+/- 23 vs
      30+/- 6, P=0.002]. The ratio of serum beta-CTX/PINP decreased in the effective
      group, and the difference was statistically significant. There was no significant
      difference in serum beta-CTX, PINP concentration and beta-CTX/PINP ratio before
      and after treatment in the uneffective group. Conclusions: There is a difference
      between newly diagnosed MMBD and bone metastases in serum beta-CTX, which might
      be helpful for differential diagnosis, and the ratio of beta-CTX/PINP is
      positively correlated with the severity of MMBD, which might be used to evaluate
      the severity of bone disease and have a certain monitoring significance for the
      treatment of MM.

PMID- 30220145
TI  - [Analysis of antimicrobial resistance and risk factors of community-onset
      methicillin-resistant staphylococcus aureus infection].
AB  - Objective: To analyze risk factors and drug resistance of community-onset
      methicillin-resistant staphylococcus aureus (CO-MRSA) infection through the
      investigation of patients infected with CO-MRSA. Methods: The clinical data of 97
      cases infected with community-onset staphylococcus aureus (COSA) was collected in
      this hospital from July 2016 to June 2017. Epidemiological survey method and the
      variables were determined according to expert consultation, literature and
      practical work experience. Results: Among 97 patients infected with COSA, the
      diagnosis rate of CO-MRSA was 21.65%(21/97). The drug sensitivity results showed
      that: CO-MRSA was high resistant to erythromycin, tetracycline and clindamycin,
      and the drug resistance rate exceeded 50%. Multiple variables were analyzed by
      Logistic regression. The usage of antimicrobial agents in the past three months
      and the history of hospitalization within one year were the independent risk
      factors. The MRSA infection rate was 57.89%(11/19) of the persons who had taken
      antibacterial agents in the recent three months.The MRSA infection rate was
      48.28%(14/29) of the persons who had been hospitalized in the past one year. OR
      value of two risk factors was respectively 10.006(95%CI: 2.200-45.519, P=0.030)
      and 11.519(95%CI: 2.405-55.177, P=0.002). Conclusions: Most COSA is sensitive to
      methicillin, but CO-MRSA is multidrug resistant and has more risk factors. The
      clinicians should reasonably use the antibacterial agents according to the drug
      sensitivity in order to prevent the occurrence of multidrug resistant MRSA.

PMID- 30220146
TI  - [Influence of celastrol on toll-like receptor 4-mediated signaling pathway in the
      free fatty acids-induced HepG2 cells].
AB  - Objective: To investigate the effect and mechanism of celastrol on free fatty
      acids (FFAs)-induced HepG2 cells. Methods: Cultured human HepG2 cells were
      transfected with toll-like receptor 4 (TLR4) siRNA, and the interference
      efficiencies were examined by real-time PCR. HepG2 cells were treated with FFAs
      and celastrol, and the untreated cells were used as a normal control (NC).
      Deposition of lipids in the HepG2 cells were visualized by Oil Red O staining.
      The protein expression of TLR4 and downstream inflammatory mediators [myeloid
      differentiation factor 88 (MyD88), nuclear factor (NF)-kappaBp65, interleukin
      (IL)-1beta and tumor necrosis factor alpha (TNF-alpha)] in the HepG2 cells were
      determined by Western blotting. The significance of the data obtained was
      evaluated using analysis of variance (ANOVA). Results: Red lipid droplets were
      extensively deposited in HepG2 cells after 0.5 mmol/L FFAs induction and
      significantly decreased in the celastrol-treated group. The protein expression of
      TLR4 and downstream inflammatory mediators (MyD88, NF-kappaBp65, IL-1beta and TNF
      alpha) in the FFAs-induced HepG2 cells increased significantly compared with
      those of the NC group (all P<0.05), and were suppressed in TLR4 siRNA-treated and
      celastrol-treated group (TLR4: 0.69+/-0.14, 1.63+/-0.12 vs 2.46+/-0.23; MyD88:
      1.21+/-0.12, 1.35+/-0.18 vs 1.62+/-0.19; NF-kappaBp65: 1.69+/-0.14, 1.54+/-0.36
      vs 2.19+/-0.47; IL-1beta: 1.51+/-0.16, 1.45+/-0.38 vs 1.82+/-0.27; TNF-alpha:
      1.60+/-0.14, 1.41+/-0.29 vs 1.88+/-0.19) (all P<0.01). Co-treatment with TLR4
      siRNA and celastrol further reduced the expression of inflammation mediators
      compared with those of the TLR4 siRNA-treated group (MyD88: 1.09+/-0.23 vs 1.21+/
      0.12; NF-kappaBp65: 1.24+/-0.20 vs 1.69+/-0.14; IL-1beta: 1.28+/-0.31 vs 1.51+/
      0.16; TNF-alpha: 1.10+/-0.29 vs 1.60+/-0.14) (all P<0.01). Conclusion: Celastrol
      exerts its protective effect partly via inhibiting the TLR4-mediated signaling
      pathways in the steatotic HepG2 cells.

PMID- 30220147
TI  - [Pay attention to evaluation and management of sleep disorders in patients with
      cognitive impairment].

PMID- 30220148
TI  - [Screening of the SETX gene in sporadic amyotrophic lateral sclerosis patients of
      Chinese origin].
AB  - Objective: To investigate all coding regions of amyotrophic lateral sclerosis
      (ALS)-related gene Senataxin (SETX) in sporadic amyotrophic lateral sclerosis
      patients of Chinese origin. Methods: From January 2010 to December 2014, the
      peripheral venous blood samples and clinical data were collected from 311
      patients with sporadic amyotrophic lateral sclerosis (SALS) and 311 healthy
      controls who were of Chinese ancestry from the Department of Neurology, Chinese
      PLA General Hospital.Genomic DNA was extracted from peripheral venous blood of
      all participants using standard methods. The coding regions of SETX were
      amplified by polymerase chain reaction (PCR) and screened for mutations using
      next-generation sequencing technology. The online software SIFT and PolyPhen-2
      were used to analyze the conservation of an altered amino acid and predict the
      potential pathogenicity of identified mutations. The SPSS 22.0 software was used
      to analyze the clinical feature of all participants. Results: Tenkinds of rare
      and one novel nonsynonymous mutations were identified and were absent in 311
      controls. Twelve (3.86%) patients carried one SETX gene mutation. Five (1.61%)
      out of above-mentioned 12 patients carried highly pathogenic mutations including
      p. Pro1868Leu (c.5603G>A), p. Pro1331Leu (c.3992G>A), p. Glu756Val (c.2267T>A),
      p. Leu564Val (c.1690A>C), and p. Asn144Ser (c.431T>C). Patients carried SETX
      mutations were not different from other patients in onset age. Conclusion:
      Mutations in SETX are likely to be a pathogenesis for Chinese sporadic
      amyotrophic lateral sclerosis.

PMID- 30220149
TI  - [Statistical parametric mapping analysis of 18F-FDG PET in Parkinson's disease
      with mild cognitive impairment].
AB  - Objective: To investigate the characteristics of cerebral metabolism associated
      with mild cognitive impairment (MCI) Parkinson's disease (PD), cognitive normal
      PD and normal control to find a PET biomarker for the diagnose and estimate of PD
      MCI. Methods: Forty-seven patients diagnosed with PD (included 15 with mild
      cognitive impairment) and 20 control subjects were enrolled. All the subjects
      were evaluated with FDG-PET and clinical scale. The statistical parametric
      mapping (SPM) were analyzed to determine metabolic patterns that may be useful in
      differentiating between the three groups. Results: SPM analysis showed that
      significant hypometabolism were observed in both side of front lobe, parietal
      lobe, left temporal lobe and left occipital lobe; in the contrast, the relative
      hypermetabolism had been observed in the cerebellum, vermis, hippocampus and
      supplement motor area (SMA) in patients with PD-MCI. PD without MCI showed
      hypometabolism in both side of front lob, caudate and putamen. PD-MCI showed that
      the significant hypermetabolism were in the insular and cerebellum while
      hypometabolism were in the both side of occipital compared to PD without MCI.
      Conclusion: A voxel-by-voxel based SPM method i. e. SPM8 analysis by PET scan is
      an effective way to analysis the FDG uptake pattern of PD patients. The
      hypermetabolism in the insula and cerebellum and hypometabolism in the both side
      of occipital may be a biomarker for make a diagnosis of PD-MCI.

PMID- 30220150
TI  - [Neuroimaging characteristics of cryptogenic stroke with and without patent
      foramen ovale].
AB  - Objective: To explore the neuroimaging characteristics associated with the
      presence of patent foramen ovale(PFO) for patients with cryptogenic stroke.
      Methods: We retrospectively collected the clinical and imaging data of
      cryptogenic stroke patients with PFO and without PFO from Henan Province People's
      Hospital from January 1, 2013 to June 30, 2017. Lesion patterns and pertinent
      vascular territory were compared between the two groups. Multivariate logistic
      regression analysis was used to explore the independent predictors for the
      presence of PFO. Results: A total of 54 cryptogenic stroke patients with PFO and
      50 cases without PFO were recruited. Compared with PFO(-) stroke group, more
      patients in PFO(+ ) stroke group had migraine(P=0.036), and patients in PFO(+ )
      stroke group had higher Risk of Paradoxical Embolism(RoPE) score(P=0.030). The
      lesion pattern of PFO(+ ) stroke was more frequently observed as multiple lesions
      in multicirculatory (P=0.035), and infarcts were more likely to be distributed in
      the vertebrobasilar artery territory (P=0.041); the most frequently involved
      vessel was the posterior cerebral artery region (P=0.006). More patients with
      PFO(+ ) stroke had old silent stroke lesion(P=0.021). On multivariate analysis,
      infarction distributed in the posterior cerebral artery region(OR=4.292, 95% CI
      1.469-12.543, P=0.008), silent stroke lesion (OR=6.688, 95% CI 1.277-35.029,
      P=0.024), and high RoPE score (OR=1.393, 95% CI 1.026-1.893, P=0.034) were
      independent parameters that could predict the presence of PFO. Conclusions:
      Multiple lesions in multicirculatory and the posterior predominance are
      neuroimaging characteristics of cryptogenic stroke with PFO. Infarction
      distributed in the posterior cerebral artery region, silent stroke lesion and
      high RoPE score are independent predictors of the presence of PFO.

PMID- 30220151
TI  - [Clinical observation of postprandial hypotension in patients with hypertensive
      and coronary heart disease].
AB  - Objective: To explore the prevalence and clinical characteristics of postprandial
      hypotension(PPH) in patients with essential hypertension and coronary heart
      disease. Methods: A total of 197 patients with essential hypertension and
      coronary heart disease, who had been treated in the First Department of
      Cardiology of the Second Hospital of Hebei Medical University from December, 2013
      to December, 2014 were included. The patients' blood pressure before breakfast,
      lunch and dinner and 30, 60, 90, 120 minutes after the meal were monitored.
      Subjects were classified into PPH group (n=37) and non-PPH group (NPPH, n=160)
      according to postprandial decrease in systolic blood pressure, to explore the
      clinical characteristics and related factors and the major adverse cardiac and
      cerebral vascular events of PPH. Results: Among 197 patients, 37 cases (18.8%)
      showed at least once postprandial decline in systolic blood pressure greater than
      and equal to 20 mmHg. The incidence of PPH after breakfast and dinner were higher
      than lunch (P<0.05). There was no significant difference in the incidence of PPH
      among different age groups, among patients accompanied with different diseases,
      and among patients with different dining position (all P>0.05). According to the
      baseline systolic blood pressure, patients can be divided into 4 groups(<120
      mmHg, 120-129 mmHg, 130-139 mmHg, >140 mmHg), the higher the level of the
      baseline systolic blood pressure was, the higher the incidence of PPH was. And
      the incidence of major adverse cardiac and cerebral vascular events in patients
      during hospitalization were increased by PPH. Conclusions: The prevalence of PPH
      in the patients with essential hypertension and coronary heart disease is 18.8%.
      The incidence of PPH after breakfast and dinner is higher than lunch. The
      baseline systolic blood pressure is considered to be the risk factor of PPH. And
      PPH could lead to an increase of the incidence of major adverse cardiac and
      cerebral vascular events.

PMID- 30220152
TI  - [Efficacy and safety of licartin with repeated administration in treatment of HCC
      patients after liver transplantation].
AB  - Objective: To evaluate the efficacy and adverse reactions of licartin with
      repeated administration in treatment of hepatocellular carcinoma (HCC) patients
      after liver transplantation. Methods: Clinical data of 60 patients after liver
      transplantation with licartin in Tianjin First Central Hospital from December
      2012 to December 2016 were collected and analyzed.The patients were divided into
      A group(received single therapy, n=45)and B group(received repeated therapy with
      equal or greater than twice, n=15). The results of blood routine examination,
      liver function and thyroid function between the two groups(1 week before
      treatment, 2, 4 and 8 weeks after treatment) were compared. Survival time and
      adverse reactions were statistically analyzed. Results: There was no significant
      statistical difference on age, gender and AFP between the two groups(all P>0.05).
      Compared to baseline level 1 week before treatment, platelet levels were reduced
      2 weeks after treatment, and gradually recovered to baseline level at 8
      weeks(F=50.42 and 61.71, all P<0.05); 4 weeks after treatment, the alanine
      aminotransferase and total bilirubin levels were increased to a certain extent
      and recovered to baseline at 8 weeks(F=5.42 and 3.39, 8.95 and 6.84, all P<0.05).
      Thyroid function injury ratio for the two groups were 8.9% and 8.6%. No serious
      adverse reactions occurred, and mild adverse reactions could be tolerated with
      spontaneous remission or symptomatic treatment. There was no significant
      statistical difference between the two groups(chi2=0.459-1.0, all P>0.05). The
      median survival time was 34.0 months for A group, the 6-, 12-, 18-, 24-, 36- and
      48-month overall survival rates for the two groups were 93.3%, 86.6%, 73.3%,
      62.2%, 48.9%, 33.3% and 100%, 93.3%, 86.7%, 80.0%, 66.7%, 66.7%, respectively
      (chi2=4.324, P=0.038). HCC in situ recurrence rate for the two groups were 15.6%
      and 13.3%(chi2=1.0, P=0.601). The incidence of hepatocellular metastasis for the
      two groups were 22.2% and 20.0%(chi2=1.0, P=0.585). Conclusion: Repeated licartin
      administration could prevent HCC recurrence and prolong survival with
      satisfactory safety.

PMID- 30220153
TI  - [Comparison of spontaneous correction in thoracic curves after anterior versus
      posterior selective fusion in Lenke type 5C adolescent idiopathic scoliosis].
AB  - Objective: To analyze the long-term results and the influence factors of
      spontaneous correction of unfused thoracic curves in anterior and posterior
      selective fusions in Lenke type 5C adolescent idiopathic scoliosis (AIS).
      Methods: From January 2005 to December 2011, 89 Lenke type 5C AIS patients with a
      minimum of 5-year follow-up who underwent thoracolumbar/lumbar (TL/L) selective
      fusion in Spine Surgery of Nanjing Drum Tower Hospital were reviewed.Forty-six
      patients underwent anterior fusion (anterior group), while 46 underwent posterior
      fusion (posterior group). The following radiological parameters were measured and
      analyzed at pre-operation, post-operation, and latest follow-up: curve magnitude
      of primary thoracolumbar/lumbar and secondary thoracic curve, trunk shift,
      thoracic apical vertebral translation, upper instrumented vertebra tilt, thoracic
      kyphosis, proximal junctional angle, sagittal vertical axis. Independent sample t
      test was used to compare the above parameters between the two groups. Results:
      Compared with those in posterior group, anterior group were found with less
      fusion levels (5.4+/-0.6 vs 5.9+/-0.8, t=3.318, P=0.001) and longer operation
      time[(276+/-28)min vs (186+/-36)min, t=13.101, P<0.001]. Immediately after
      surgery, the spinal deformity was significantly corrected in the two groups. The
      mean spontaneous correction rates of the minor curve were 50%+/-21% and 56%+/-20%
      in anterior and posterior groups, respectively (t=1.489, P=0.140). After a mean
      follow-up of (6.8+/-1.7) years in anterior group and (6.3+/-1.3) years in
      posterior group, the spontaneous correction rate of minor curve was maintained at
      46%+/-22% and 49%+/-19%, respectively (t=0.703, P=0.484), with no significant
      correction loss. Other radiographic parameters were also stably maintained.
      According to the correlation analysis, the spontaneous correction rate was
      significantly correlated with upper instrumented vertebra (UIV) tilt in both
      groups (anterior: r=-0.526, posterior: r=-0.399, both P<0.05). Conclusions: Both
      anterior and posterior selective fusion can achieve satisfactory spontaneous
      correction of unfused thoracic curves in Lenke type 5C AIS, with no significant
      difference between the two surgical approaches. UIV tilt is a key influence
      factor of spontaneous correction of thoracic curves.

PMID- 30220154
TI  - [Repairing the bone and skin defect of foot after improved toe-to-finger
      reconstruction utilizing periosteal perforator bone-skin flap of proximal
      anterior tibial artery].
AB  - Objective: To evaluate the clinical outcome of repairing donor site of foot after
      improved toe-to-finger reconstruction utilizing periosteal perforator bone-skin
      flap of proximal anterior tibial artery. Methods: Twelve patients of toe defect
      after reconstruction were repaired from March, 2015 to June, 2017 utilizing
      periosteal perforator bone-skin flap of proximal anterior tibial artery in the
      Department of Hand and Foot Microsurgery of Xin'an Hospital, Dongguan City.Of
      which, there were 7 cases of great toe defect with fibular side of phalanx ungual
      and skin, 5 cases of second toe defect with proximal interphalangeal joints and
      the partial bone accompanied the great toe defect.Double bone flaps of one
      pedicles were used to repair first and second phalanx defect in 5 cases.The skin
      injured area: 5.5 cm*2.5 cm to 6.5 cm*10.0 cm. Bone defect size of great and
      second toe were 1.5 cm*1.0 cm*0.8 cm to 1.7 cm*1.0 cm*1.0 cm and 2.5 cm*1.0
      cm*1.0 cm to 4.0 cm*1.0 cm*1.0 cm, respectively.The flap size ranged from 6.0
      cm*3.0 cm to 6.5 cm*12.0 cm, and the bone flap size ranged from 1.5 cm*1.0
      cm*0.8cm to 1.7 cm*1.0 cm*1.0 cm(great toe) and 2.0 cm*1.0 cm*1.0 cm to 3.5
      cm*1.0 cm*1.0 cm(second toe). The wound of donor site of the leg was directly
      combined or local skin transfer sutured with 8 cases, skin-grafting in 4 cases.
      Results: All the bone-skin flaps survived.After 6-27 months of follow-up, the
      great toe flaps were found with normal color, good texture and moderate
      thickness, the two-point discrimination was 7-10 mm. The donor site of the leg
      showed little influence with normal function.No pain and discomfort in the foot
      were recorded, and the patients walked well.The healing time of bone flap was
      from 1.5 to 4 months, with an average of 2.5 months.Using the Maryland Foot
      Score, 5 cases of 7 feet got excellent and 2 cases of 2 feet got good result in
      the great toe group (7 cases of 9 feet), the good rate was 100%.Three cases got
      excellent and two cases got good result in the combined reconstruction group (5
      cases), the good rate was 100%. Conclusion: Repairing donor site of foot after
      improved toe-to-finger reconstruction utilizing periosteal perforator bone-skin
      flap of proximal anterior tibial artery can also repair bone and skin defect of
      the great and the second toe, keep the great and the second toe, and restore the
      appearance and function of the first and the second toe at utmost.

PMID- 30220155
TI  - [Cement augmentation for vertebral osteolytic metastatic lesions: an evaluation
      on postoperative CT].
AB  - Objective: To evaluate the effectiveness of cement augmentation on the osteolytic
      lesion in patients with vertebral metastasis. Methods: A total of consecutive 132
      patients with 268 vertebral metastatic lesions treated with PVP from January 2008
      to December 2016 in Zhongda Hospital were enrolled in this study. Retrospective
      analysis of preoperative, postoperative 3 days, 3 months, 6 months, 12 months and
      >= 18 months imaging data on CT, the local control and progression of the tumor
      were evaluated by MDA response criteria. The local control rates were compared
      between the groups with the different rate of cement filling by Chi2-test.
      Results: Vertebroplasty procedures were performed successfully in all 268
      vertebrae under DSA guidance, and the mean volume of PMMA injected in each
      vertebra was 0.7-8.5(3.9+/-1.5)ml.The rate of local control at 3 months, 6
      months, 12 months and >=18 months after PVP was respectively 98.9%, 95.1%, 91.8%,
      and 85.2%, the difference was statistically significant(all P<0.05). The local
      control rate showed a statistically significant relationship to the groups with
      the rate of cement filling at 6 months, 12 months and >=18 months after PVP, but
      there was no statistical difference at postoperative 3 months. The rate of local
      control was higher in 68 patients with lung or gastrointestinal cancer than in 17
      patients with liver or kidney cancer at 3 months, 6 months and 12 months, the
      difference was statistically significant (P<0.05). Conclusion: Cement
      augmentation has a local anti-tumor effect on vertebral osteolytic metastatic
      lesion, and the anti-tumor effect will decrease as the follow-up time extended.

PMID- 30220156
TI  - [Virtual planning and 3D printing modeling for mandibular reconstruction with
      fibula free flap].
AB  - Objective: To evaluate the use of virtual planning and 3D printing modeling in
      mandibular reconstruction and compare the operation time and surgical outcome of
      this technique with conventional method. Methods: Between June 2013 and June
      2017, A total of 18 patients underwent the mandibular reconstruction with fibula
      free flap in the Affiliated Hospital of Qingdao University.Among 18 patients,
      there were 11 males and 7 females with an average age of 36.5 years (21-73
      years). Nine patients underwent vascularized fibula flap mandibular
      reconstruction using virtual planning and 3D printing modeling.Titanium plates
      were pre-bent using the models and cutting guides which were used for
      osteotomies.Another 9 patients who underwent mandibular reconstruction using
      fibula flap without aid of virtual planning and 3D printing models were selected
      as control group. The operation time was recorded and compared in two groups.
      Accuracy of reconstruction was measured by superimposing the preoperative image
      onto the postoperative image of mandible. The selected bony landmark, distance
      and angle were measured. Results: The mean total operation time were 4.7
      6.2(5.5+/-0.5) h in computer-assisted group and 5.6-7.5(6.6+/-0.7) h in
      conventional group, respectively. The operation time was shorter in computer
      assisted group. The difference between the preoperative and postoperative
      intercondylar distances, intergonial angle distances, anteroposterior distances
      were(2.6+/-1.4)vs(4.4+/-1.6)mm, (2.9+/-1.2)vs(4.7+/-1.7)mm, (4.2+/-1.4) vs(5.9+/
      1.8)mm in the computer-assisted and conventional group, respectively. The
      differences between the preoperative and postoperative mandible were smaller in
      the computer-assisted group. Conclusions: Virtual planning and 3D printing
      modeling have the potential to increase mandibular reconstruction accuracy and
      reduce operation time. We believe that this technology for mandibular
      reconstruction in selected patients can significantly improve the quality of
      reconstruction.

PMID- 30220157
TI  - [Clinical evaluation of dry chemical enzyme method for detecting Neisseria
      gonorrhoeae and analysis of external quality assessment results].
AB  - Objective:Neisseria gonorrhoeae in female cervix sample was detected by dry
      chemical enzymatic method and culture method. The detection effects of two
      detection methods were analyzed to provide reference for clinical detection. At
      the same time, strains were separated and identified to evaluate reliability of
      different methods. Methods: During October 2015 to December 2017, 8 860 samples
      of female cervix from the Third Affiliated Hospital of Zhengzhou University and
      Henan Provincial Peoples Hospital were detected by dry chemical enzymatic method
      and culture method. Because of the possible leak detection by culture method, the
      inconsistent results were supplemented by real-time PCR assay. The data were
      analyzed by SPSS 19.0. Fifteen strains of external quality assessment of
      Neisseria gonorrhoeae identification and validation during 2015 to 2017 years
      were identified by latex chromatography, culture method, dry chemical enzyme
      method and PCR- fluorescent probe method. Results: The positive rates of dry
      chemical enzymatic method and culture method for detection of Neisseria
      gonorrhoeae were 0.88% (78/8 860) and 0.41% (36/8 860), respectively. Among
      these, 26 samples were tested positive by dry chemical enzymatic method which
      were consistent with real-time PCR assay. Meanwhile, the culture method was
      negative. Dry chemistry enzyme method external quality assessment results of 3
      years were accurate. Conclusion: The positive rate of dry chemical enzymatic
      method was markedly higher than that of culture method (P<0.05). The dry chemical
      enzymatic method, while exhibiting a high specificity, had high detection rate
      compared to culture method. And external quality assessment results are accurate.
      The clinical coincidence rate of dry chemical enzymatic detection was higher.

PMID- 30220158
TI  - [Application of transperineal pelvic floor ultrasonography in the diagnosis of
      female stress urinary incontinence].
AB  - Objective: To explore the application of transperineal pelvic floor
      ultrasonography in the diagnosis of female stress urinary incontinence(SUI).
      Methods: From March 2017 to December 2017, 60 patients diagnosed with SUI by
      department of gynecology, Xiangya Hospital of Central South University were
      selected as the case group, and 30 cases of normal women in the same period were
      selected as the control group. All subjects in both groups were examined by
      transperineal pelvic floor ultrasonography, that is, to be measured the bladder
      neck descent(BND), the urethral inclination angle(UIA), the posterior
      urethrovesical angle(PUVA) and the levator hiatus area(LHA) in resting state and
      during Valsalva maneuver. Results: (1)The differences in the measured values of
      the two groups were statistically significant(P<0.05). (2)The receiver operating
      characteristic curve(ROC) was used to find the cut-off values of SUI: when
      BND>31.5 mm; in Valsalva state, UIA>33.5 degrees , PUVA>150.5 degrees  and
      LHA>20.6 cm2, with their sensitivity of 77.6%, 71.4%, 68.3% and 61.4%,
      respectively; the specificity of 68.9%, 74.6%, 73.9% and 78.0%, respectively. The
      area under the curve(AUC) were 0.753, 0.812, 0.721 and 0.712, respectively, when
      combined analysis of these indexes, reaching to 0.912. Conclusions: (1)
      Transperineal pelvic floor ultrasonography has a certain diagnostic value for
      SUI. (2)Combined analysis of various ultrasonic parameters can significantly
      improve the diagnostic efficiency of SUI.

PMID- 30220159
TI  - [Targeting diagnosis and treatment value of chelating anti-IL-1beta mAb-SPIONs in
      temporal lobe epilepsy model].
AB  - Objective: In order to study the diagnosis and treatment value of chelating anti
      IL-1beta mAb-SPIONs in temporal lobe epilepsy model induced by lithium chlorid
      and pilocarpine. Methods: Forty-five temporal lobe epilepsy model rats were
      randomly and equally divided into saline group, plain-SPIONs group, anti-IL-1beta
      mAb-SPIONs group. Each group was injected with equal particles at day 3 and day
      14 after the onset of seizures. MRI were conducteds before and 4 hours after
      particles injection and T2 values were measured. The distribution of iron
      particles in the epileptic tissue was observed and the neuronal loss, astrocyte
      proliferation and microglia activation were detected. The expressions of IL-1beta
      and NF-kappaBp65 in each group were detected meanwhile. Results: At day 14 after
      seizure, the value of T2 was 84+/-14 after injecting anti-IL-1beta mAb-SPIONs.
      Compared with the control group, the value of T2 obviously declined. These
      phenomena of neuron loss, astrocyte proliferation and microglia activation had
      been improved obviously. IL-1betaand NF-kappaBp65 expression also significantly
      reduced. Conclusion: Anti-IL-1beta mAb-SPIONs can penetrate blood brain barrier
      and plays an important role in targeting positioning and targeting therapy in
      temporal lobe epilepsy.

PMID- 30220160
TI  - [The concept and application of Intelligence Medicine].

PMID- 30220161
TI  - [Definition changes of acute respiratory distress syndrome over the past 50
      years].

PMID- 30220162
TI  - [Personalized mechanical ventilation guided by pulmonary mechanics in acute
      respiratory distress syndrome patients].

PMID- 30220163
TI  - [Extracorporeal membrane oxygenation: hope of severe acute respiratory distress
      syndrome].

PMID- 30220164
TI  - [Heterogeneity of pathophysiological characteristics of acute respiratory
      distress syndrome].

PMID- 30220165
TI  - [Medication and biologic treatment of acute respiratory distress syndrome].

PMID- 30220166
TI  - [Clinical analysis of hepatic perivascular epithelioid cell neoplasm: a report of
      eleven cases].
AB  - Objective: To investigate the clinical features, diagnosis and therapy of hepatic
      perivascular epithelioid neoplasms (PEComa). Methods: The clinical data of eleven
      patients with hepatic PEComa who received surgical treatment at Shengjing
      Hospital Affiliated to China Medical University from April 2012 to October 2017
      were collected. The clinical manifestations, imaging features, diagnostic and
      therapeutic strategies, pathologic features, prognosis were analyzed. Results:
      The patients aged from 35 to 55 years (mean: 47 years , 3 males and 8 females).
      Two patients had epigastric pain, the others rarely had any clinical symptom.
      Hepatitis C virus (HCV) infection was present in one patient 9.09%(1/11), the
      rate of correct diagnosis by imageological examination before operation was only
      9.09%(1/11). All patients received a surgical resection, the final diagnosis of
      hepatic PEComa was made with pathology and immunohistochemistry. The antibodies
      used for immunohistochemistry varied from patient to patient. The positive rates
      of Melan A, HMB45, smooth muscle actin and S-100 were 100%(10/10), 90%(9/10),
      77.8%(7/9)and 33.3%(3/9) respectively, the Ki-67 positive index was 1%-10%. One
      patient died after surgery because of hemorrhage, other ten patients received
      long-term follow-up(5-71 months), and no recurrence or metastasis was observed.
      Conclusion: Hepatic PEComa is a rare mesenchymal neoplasm which expresses both
      melanocytic and myogenic markers. Middle aged females are susceptive to hepatic
      PEComa, and patients rarely have any specific clinical presentation. It's
      difficult to make a correct diagnosis before operation. The diagnosis finally
      depends on the pathological examination. Surgical resection and close follow-up
      are the principal methods for the management of hepatic PEComa.

PMID- 30220167
TI  - [The role of prophylactic use of pegylated recombinant human granulocyte colony
      stimulating factor(PEG-rhG-CSF) in breast cancer receiving adjuvant
      chemotherapy].
AB  - Objectives: To investigate the efficacy and safety of prophylactic use of
      pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in
      breast cancer receiving docetaxel as adjuvant chemotherapy. Methods: A total of
      58 patients with breast cancer receiving adjuvant chemotherapy with docetaxel
      were included between January 2014 to October 2017. Prophylactic use of PEG-rhG
      CSF was administered.Patients were further divided into two groups according to
      the frequency of PEG-rhG-CSF use: frequent use group (>=3 cycles) and non
      frequent use group (<3 cycles). Results: There were significant differences in
      the incidence rates of grade 3/4 neutropenia between the prophylactic group and
      non-prophylactic group in cycle 1-3(P<0.05). Less febrile neutropenia (FN) was
      also noted in the prophylactic group compared with the non-prophylactic group in
      cycle 1 and cycle 3 (P<0.05). Grade 3/4 neutropenia and FN were less in the
      frequent use of group compared with the non-frequent use group(P<0.001). The most
      common side effects of PEG-rhG-CSF included fatigue (10.2%), bone joint
      pain(50.8%), and 2 patients (3.4%) refused further treatment because of bone
      joint pain. Conclusions: PEG-rhG-CSF should be prophylactically used for
      preventing neutropenia and febrile neutropenia in breast cancer patients
      receiving adjuvant chemotherapy with docetaxel regimen.

PMID- 30220168
TI  - [Clinical characteristics and prognosis analysis of 46 cases of newly diagnosed
      localized head and neck rhabdomyosarcoma].
AB  - Objective: To analyze the clinical characteristics and prognosis of newly
      diagnosed localized head and neck rhabdomyosarcoma. Methods: Cases of newly
      diagnosed localized head and neck rhabdomyosarcoma between January 2006 and
      December 2016 were analyzed retrospectively. The clinical features of the
      patients were described. The Kaplan-Meier method was used to analyze the survival
      rate under different combined modality therapy and the survival rate with or
      without chemotherapy. The prognostic factors were analyzed by Cox model. Results:
      A total of 46 patients were included in this study. Among them, the median follow
      up time was 77 months and the median relapse free survival time was 13 months.
      The relapse free survival time of 5 cases with inadequate local treatment and
      without combined chemotherapy was 5 months as control, and it was 7 months
      (P=0.110) in 11 cases with adequate local treatment without combined
      chemotherapy. Then in 7 cases with inadequate local treatment combined with
      chemotherapy and 23 cases with adequate local treatment combined with
      chemotherapy, it was 13 months (P=0.007) and 21 months (P<0.001), respectively.
      The median relapse-free survival time of chemotherapy patients was significantly
      longer than that of those without chemotherapy (21 vs 6 months, P=0.018). The
      effect of combined modality therapy was evaluated according to the adequacy of
      local treatment and whether to receive systemic chemotherapy, and the combined
      modality therapy degree was the independent prognostic factor in Cox's
      proportional hazards regression model (P=0.004). Conclusions: Rhabdomyosarcoma in
      head and neck is a highly malignant tumor with high relapse rate and easy
      metastasis. In patients with tolerable condition, systemic chemotherapy and
      adequate combined modality therapy are recommended to improve relapse-free
      survival.

PMID- 30220169
TI  - [Clinical characteristics of silent pheochromocytoma].
AB  - Objective: To summarize the clinical characteristics of silent paraganglioma.
      Methods: A total of 247 pheochromocytoma cases in Peking University First
      Hospital between January 1993 and December 2015 were analyzed retrospectively.The
      cases were divided into two groups according to whether they had hypertension:
      non-silent group (193 cases) and silent group (53 cases), then the clinical
      characteristics between the groups were compared, and the clinical features of
      silent pheochromocytoma were reviewed. Results: There were 53 silent
      pheochromocytoma cases in this study, which accounted for 21.5% (53/247), and
      imaging was the main way to find the tumor. Forty-one in 53 cases (77.4%) located
      in adrenal gland, in which 31 cases (75.6%) were benign and 2.3-8.0 cm in
      diameter, while 10 cases (24.4%) were malignant and 3.5-12.0 cm in diameter.
      Twelve in 53 cases (22.6%) located in extra-adrenal tissue, in which 4 cases were
      benign and 2.0-5.5 cm in diameter, while 8 cases were malignant and 5.0-10.5 cm
      in diameter. With the tumor diameter increased, the malignant rate increased: 1
      in 8 cases in diameter<3 cm, 2 in 12 cases in diameter 3-5 cm, 15 in 33 cases in
      diameter>5 cm were malignant. There was no significant difference in age, sex,
      tumor location, benign or malignant rate between the two groups (all P>0.05).
      Compared with the non-silent group, the proportion of tumor size>=5 cm in silent
      group was significantly higher (62.3% vs 45.9%, P=0.034), and the incidence of
      hyperglycemia and the concentrations of norepinephrine and epinephrine were lower
      (all P<0.05) in silent group.Misdiagnosis was common in silent group, and up to
      35.8% (19/53) had not been diagnosed correctly before operation. Twenty-one in 53
      (39.6%) silent pheochromocytoma cases occured severe intra-operative blood
      pressure fluctuation. Conclusions: Silent pheochromocytoma was not uncommon and
      imaging was the main way to find it. The tumor size was always big and
      misdiagnosis was common, especially extra-adrenal tumors. Therefore, regardless
      of the adrenal or extra-adrenal tumors, especially in diameter>3.0 cm but with
      normal blood pressure, the possibility of silent pheochromocytoma should be
      considered. In order to reduce misdiagnosis and intra-operative blood pressure
      fluctuations, preoperative diagnosis and preparation, as well as intra-operative
      monitoring should be fully made.

PMID- 30220170
TI  - [A comparative study of cold snare and hot snare resection of small colorectal
      polyps].
AB  - Objective: To compare the effect of cold snare and hot snare on the resection of
      small colorectal polyps, and to explore the clinical value of cold snare
      technique in removing colorectal polyps. Methods: From September 1, 2017 to
      January 31, 2018, 206 cases of patients with colorectal polyp resection in the
      Department of Gastroenterology of Peking University International Hospital were
      studied. During this period, according to the standard, 103 cases of patients
      (158 polyps) were in the cold snare group, and 103 patients (180 polyps) were
      randomly selected as control group from patients of the hot snare group. The
      related clinical data were analyzed retrospectively. The location, shape, size,
      polypectomy time, pathological type, complete resection rate, specimen recovery
      rate, complications and related costs of the two groups of polyps were compared.
      Results: The polypectomy time of the cold snare group was shorter than that of
      the hot snare group.The difference was statistically significant (Z=-11.727,
      P<0.001). The related cost of the perioperative period of the cold snare group
      was lower than that of the hot snare group.The difference was statistically
      significant (Z=-12.680, P<0.001). There were no statistically significant
      differences in the number of polyps/case, size, shape, pathological
      classification, complete resection rate, specimen recovery rate, and
      perioperative complications of the patients in the two groups(P>0.05).
      Conclusions: The operation time of cold snare technique in colorectal polyps (6-9
      mm in diameter) is shorter and the cost is lower, which is worthy of clinical
      promotion.

PMID- 30220171
TI  - [The impact of genetic variation of KDR on clinical outcomes of advanced
      colorectal cancer patients treated by first line bevacizumab based regimens].
AB  - Objective: To investigate the association between kinase insertion region
      receptor (KDR) gene genetic variation and the efficacy of bevacizumab in patients
      with advanced colorectal cancer(CRC) were investigated in this study. Methods:
      118 patients with advanced colorectal cancer who were treated by bevacizumab
      based first line regimens were included in this study. Peripheral blood and the
      biopsy tissue specimens of the CRC patients were collected for the genotyping of
      genetic variation and KDR gene expression, respectively. The univariate analysis
      of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and
      multivariate were adjusted by Cox regression analysis. Results: Located in the
      coding region, the prevalence of 889 C>T in KDR among the study population were
      as follows: CC genotype 86 cases (72.88%), CT genotype 30 cases (25.42%), TT
      genotype 2 cases (1.70%), minor allele frequency of 889 C>T is 0.14. The
      distribution of three genotypes in accordance with Hardy-Weinberg Equilibrium
      (P=0.737). There were no statistical differences in the distribution of the
      genotypes in baseline clinical data. TT and CT genotype patients were merged in
      the comparison of clinical outcomes. The clinical outcomes analysis of patients
      with different genotypes found that the objective response rates (ORR) of CT/TT
      genotypes were 34.38% and 43.02% (P=0.395), respectively. And the median
      progression free survival (PFS) of patients with CT/TT genotype and CC genotype
      were 7.5 and 9.7 months respectively, which was statistically significant
      (P=0.009). In terms of overall survival (OS), the median OS of the two genotypes
      were 19.3 and 20.1 (P=0.025), respectively. Adjusted in multivariate Cox
      regression analysis of PFS, CT/TT genotypes were an independent factor for PFS
      (OR=1.88, P=0.023). Additionally, of the 57 biopsy tissue specimens, gene
      expression analysis was conducted. And the results showed that the expression of
      KDR in cancer tissues of the patients with CT/TT genotypes were significantly
      higher than those of the CC genotype patients (P<0.001). Conclusion: Among
      advanced colorectal cancer patients treated by bevacizumab, the polymorphism 889
      C>T of KDR may impact the clinical outcomes of bevacizumab first line treatment
      by influencing the mRNA expression of KDR.

PMID- 30220172
TI  - [Effects of TLR4-PI3K-Rac1 pathway on cytoskeleton rearrangement and phagocytosis
      of macrophage].
AB  - Objective: To investigate the effects of Toll-like receptor 4 (TLR4)
      phosphatidylinositol 3-kinase (PI3K) -Ras-related C3 botulinum toxin 1 (Rac1)
      signaling pathway on macrophage cytoskeleton rearrangement and phagocytosis.
      Methods: Mouse macrophage cell line RAW264.7 was divided into blank group,
      negative control group and TLR4-RNA interference (RNAi) group. The lentivirus
      carrying TLR4 short hairpin RNA (shRNA) and nonsense control sequence were
      respectively transfected into TLR4-RNAi group and negative control group. The
      cells in blank group were not transfected. The silencing efficiency of TLR4 was
      detected by Western blot. Real-time fluorescence quantitative PCR was used to
      detect the expression of PI3K and Rac1 mRNA in each group. The expressions of
      PI3K, p-Rac1 and Rac1 protein were detected by Western blot. Cytoskeleton was
      observed by laser scanning confocal microscopy. Mean fluorescence intensity (MFI)
      and the percentage of cells phagocytosing flurescein inothiocyanate-labeled
      Eseherichina coli (FITC-E.coli) (Phagocytosed cell %) were detected by flow
      cytometry. Results: The RAW264.7 cells can be successfully transfected by TLR4
      shRNA lentivirus, and the transfection efficiency ranged from 80% to 90%. The
      silencing efficiency of TLR4 gene was (63+/-4)%. After silencing the TLR4 gene,
      the relative expression of TLR4 mRNA and protein (0.20+/-0.03, 0.37+/-0.04), PI3K
      mRNA and protein (0.64+/-0.06, 0.75+/-0.06), Rac1 mRNA, protein and p-Rac1
      protein (0.75+/-0.04, 0.76+/-0.01, 0.74+/-0.05) in TLR4-RNAi group were
      significantly lower than those in negative control group and blank group (all
      P<0.01). The change of cytoskeleton: after silencing the TLR4 gene, the celluar
      pseudopods were short and stiff, with the impaired capacity of phagocytosing FITC
      E.coli. Cells in blank group and negative control group extended good
      pseudopodia, and the capacity of phagocytosing FITC-E.coli was normal. The MFI
      and Phagocytosed cells % of TLR4-RNAi group[(7 453+/-564), (70.20+/-2.27)%]were
      significantly lower than those in the blank group and the negative control group
      (all P<0.01). Positive correlations were existed between mRNA, protein expression
      of TLR4, PI3K, Rac1 and MFI, Phagocytosed cells% (all P<0.05) in all groups.
      Conclusion: TLR4-PI3K-Rac1 pathway involves in the cytoskeleton rearrangement and
      impairs the phagocytosis of macrophages.

PMID- 30220173
TI  - [Effect and mechanism of MicroRNA-146a on TLR4 inflammatory signal pathway in the
      lung tissues of rats with mechanical ventilator-induced lung injury].
AB  - Objective: To investigate the effect and mechanism of microRNA-146a (miR-146a) on
      Toll-Like Receptor 4 (TLR4) inflammatory signal pathway in the lung tissues of
      rats with mechanical ventilator-induced lung injury. Methods: Thirty-two healthy
      male Sprague-Dawley rats were randomly divided into 4 groups (n=8 each): group A,
      normal control group, no mechanical ventilation, spontaneous breathing; group B,
      mechanical ventilation injury; group C, mechanical ventilation injury plus no
      load virus transfection; group D, mechanical ventilation injury plus virus
      transfection; in group B, C, and D, mechanical ventilation were performed,
      respiratory rate was controlled at 80 beats/min, tidal volume was 40 ml/kg,
      inhaled oxygen concentration (FiO2) was 21%, inhalation/expiration ratio was 1?2,
      positive end expiratory pressure ventilation (PEEP) was 0, each group were
      ventilated 4 hours daily, 7 days continuously to establish ventilator induced
      lung injury (VILI) rat model. Paraffin-embedded sections of lung tissue were
      stained with HE, the morphology and damage of lung tissue were observed under
      microscope. The lungs wet and dry ratio (W/D), the levels of inflammatory
      cytokines interleukin (IL)-1beta, IL-2 and tumor necrosis factor (TNF)-alpha were
      determined. Real-time PCR was used to detect the expression of TLR4 mRNA. The
      level of TLR4 protein was determined by Western blot. Results: The levels of lung
      tissue W/D and lung injury scores in group B (6.41+/-0.10, 11.38+/-0.92), group C
      (6.45+/-0.19, 11.75+/-1.04), group D (5.95+/-0.14, 7.53+/-4.78) were
      significantly increased than those in group A (4.33+/-0.08, 0.25+/-0.46), and in
      group D they were significantly decreased than group C (all P<0.01). The levels
      of IL-1beta, IL-2, TNF-alpha in group B[(36.07+/-4.28) pg/ml, (5.02+/-0.63)
      ng/ml, (382.57+/-35.41) ng/ml], group C[(35.82+/-5.47) pg/ml, (4.98+/-0.71)
      ng/ml, (375.13+/-36.95) ng/ml], group D[(27.01+/-3.18) pg/ml, (3.96+/-0.82)
      ng/ml, (297.56+/-39.08) ng/ml]were significantly increased than those in group
      A[(21.46+/-3.15) pg/ml, (2.45+/-0.17) ng/ml, (195.92+/-18.07) ng/ml], and in
      group D they were significantly decreased than group C (all P<0.01). The relative
      expression levels of TLR4 mRNA and TLR4 proteins in group B (29.57+/-5.10, 0.75+/
      0.110), group C (27.27+/-4.72, 0.77+/-0.130), group D (12.89+/-2.58, 0.48+/
      0.057) were significantly increased than those in group A (1.02+/-0.13, 0.18+/
      0.025), and in group D they were significantly decreased than group C (all
      P<0.01). There was no significant difference of all the above indicators between
      group B and C (all P>0.05). Conclusions: MiR-146a can reduce acute lung
      inflammation and TLR4 expression in lungs of rats with mechanical ventilator
      induced lung injury. MiR-146a may inhibit the inflammatory response through TLR4
      signaling pathway.

PMID- 30220174
TI  - [Effect of different genotypes of PNPLA3 I148M on hepatocyte proliferation].
AB  - Objective: To explore the influence of patatin-like phospholipase domain
      containing-3 (PNPLA3) wild type 148I/I and mutant type 148M/M on HepG2 cell
      proliferation and the relative mechanisms. Methods: HepG2 cell line stably
      overexpressing PNPLA3 148I/I, 148M/M and negative control (NC) were set up. Cell
      counting kit-8 (CCK8) assay was used to measure cell viability. Edu assay was
      used to determine the ability of cell proliferation. Western blot was used to
      detect the protein levels in the phosphatidylinositol 3-kinases (PI3K) pathway.
      Enzyme-linked immunosorbent assay (ELISA) was used to detect proliferation
      related PNPLA3 metabolites[arachidonic acid (AA) and lysophosphatidic acid
      (LPA)]. Quantitative real-time PCR was used to detect the expression level of
      prostaglandin G/H synthase 2 (PTGS2) and proliferator-activated receptor gamma
      coactivator 1-alpha (PGC1alpha) associated with PNPLA3. Results: The cell
      viability of overexpression of PNPLA3 148M/M group was about 1/3 times higher
      than that of overexpression of PNPLA3 148I/I group, and the difference was
      statistically significant[(98.02+/-1.29)% vs (71.51+/-2.89)%, P<0.001]. There was
      no significant difference between overexpression of PNPLA3 148M/M group and
      negative control group[(98.02+/-1.29)% vs (100+/-2.61)%, P=0.181]. The
      proliferative activity of overexpression of PNPLA3 148M/M group was about 1/3
      times higher than that of overexpression of PNPLA3 148I/I group, and the
      difference was statistically significant(46.46+/-1.83 vs 35.96+/-2.65, P=0.001).
      There was no significant difference between overexpression of PNPLA3 148M/M group
      and negative control group(46.46+/-1.83 vs 46.64+/-7.33, P=0.965). The PGC1alpha
      mRNA expression, total PI3K, PThr-308AKT, PSer2448-mammalian target of rapamycin
      (PSer2448-mTOR) and PGC1alpha protein expression levels in the overexpression of
      PNPLA3 148M/M group were higher than those in the overexpression of PNPLA3 148I/I
      group, but there were no significant differences in AA and LPA levels, as well as
      PTGS2 mRNA expression levels. Conclusion: PNPLA3 148M/M cell proliferation was
      stronger than PNPLA3 148I/I.

PMID- 30220175
TI  - [A retrospective study of the mortality and death-related risk factors of
      patients hospitalized for asthma exacerbation in Chinese urban areas].
AB  - Objective: To study the mortality and death-related risk factors of patients
      hospitalized for asthma exacerbation in Chinese urban areas. Methods: A
      retrospective study was carried out in 29 hospitals of 29 provinces throughout
      mainland China. Patients hospitalized for asthma exacerbation during 2013-2014 in
      each hospital were included. For each patient, information about demography,
      admission time, comorbidities, severity of diseases, intense care unit (ICU)
      admission, use of mechanical ventilation and the outcome was obtained. The
      mortality of patients hospitalized for asthma exacerbation was calculated, and
      the basic information and causes of death of the patients who died were
      summarized. The death-related risk factors and numbers of comorbidities were
      compared between the patients who survived and those who died during
      hospitalization. Results: A total of 3 240 patients (median age 57.0) were
      included and among them 8 patients (median age 68.5) died. The mortality of
      patients hospitalized for asthma exacerbation was 0.25%. All the patients who
      died were admitted during the winter and spring. One patient died of acute
      myocardial infarction, one of cardiac shock, one of tension pneumothorax, one of
      sudden death, one of respiratory failure and three of unknown causes. The average
      number of comorbidities of patients who died was 1.10, larger than that of
      patients who survived (0.83) (P>0.05). More patients had diabetes, coronary
      artery diseases and hypertension as comorbidities in the patients who died (2/8)
      than those who survived[7.6% (246/3 232), 7.6% (246/3 232), 22.6% (731/3 232),
      respectively](all P>0.05). Conclusions: The in-hospital mortality of patients
      hospitalized for asthma exacerbation of China in this study is low. The patients
      who died are much older, and with more comorbidities, and a higher percentage of
      comorbidities such as diabetes, coronary artery diseases, and hypertension.

PMID- 30220176
TI  - [Significance of intraocular biopsy in the diagnosis and treatment of eye
      diseases].
AB  - Intraocular biopsy is an important method of preoperative ophthalmic diagnosis.
      It can provide an objective basis for precise treatment of diseases, and has
      important guiding significance in the diagnosis of eye diseases, the selection of
      treatment strategies and the anticipation of prognosis. Eye biopsy technology has
      not yet been widely carried out to date in our country, and ophthalmologists
      should attach great importance to the role of intraocular biopsy in the diagnosis
      and treatment of eye diseases. Ophthalmologists should particularly improve the
      success rate of intraocular biopsy by strengthening the standardization of
      material sampling; facilitate the guiding effect of eye biopsy on the diagnosis,
      treatment and prognosis of eye diseases through efficient cooperation between
      clinician and pathologist; to improve the sensitivity and specificity of
      intraocular biopsy through organized combination of traditional cellular
      pathology with molecular pathology. (Chin J Ophthalmol, 2018, 54: 641-644).

PMID- 30220177
TI  - [The development of ophthalmology in artificial intelligence era].
AB  - Ophthalmology is a discipline that is highly dependent on the development of
      technology. Artificial intelligence is a new technological revolution, which will
      in all-round and fundamentally influence the progression of modern ophthalmology.
      Ophthalmologists should actively pay close attention to the development of
      artificial intelligence technology with great enthusiasm, and gradually realize
      the maximum utilization of artificial intelligence technology so as to facilitate
      the new development in ophthalmology. We should proactively seek for the
      opportunities of cooperating with the research organization and expert engineers
      in the area of artificial intelligence to promote the application of artificial
      intelligence in ophthalmology as soon as possible. Ophthalmology is likely to be
      radically changed by artificial intelligence technology. (Chin J Ophthalmol,
      2018, 54: 645-648).

PMID- 30220178
TI  - [Cautious choice of vitrectomy in patients with retinoblastoma].
AB  - In recent years, the treatment concept of retinoblastoma has changed from
      focusing on saving children's life to preserving the eyeballs and useful visual
      function. As a promising way to retain the eyeball, the application of vitrectomy
      in patients with retinoblastoma has long been debated. In view of the special
      anatomical structure of eyes and the biological characteristics of retinoblastoma
      cells, retinoblastoma is always prone to recurrence and metastasis after
      vitrectomy. Therefore, vitrectomy could hardly be a routine treatment and it
      should be used in retinoblastoma patients cautiously. (Chin J Ophthalmol, 2018,
      54: 649-651).

PMID- 30220179
TI  - [Histopathology manifestation and imaging characteristics of in vivo confocal
      microscopy for diagnosis of ocular surface squamous neoplasia].
AB  - Objective: To study the histopathology manifestation and imaging characteristics
      of in vivo confocal microscopy (IVCM) for diagnosis of ocular surface squamous
      neoplasia (OSSN) and analyze the reliability of IVCM in differential diagnosis
      from OSSN cases. Methods: A prospective study. Twenty-three patients (23 eyes)
      with OSSN were collected from September 2015 to November 2017 in Beijing Tongren
      Eye center. They were underwent the examinations sequentially as follows: visual
      examination; slit-lamp microscope examination and ocular surface photography;
      color fundus image; anterior segment optical coherence tomography examination;
      IVCM examination and histopathology examination after surgery. With
      histopathology diagnosis, all subjects were divided into two groups: conjunctival
      intraepithelial neoplasm (CIN) and squamous cell carcinoma (SCC). Compared with
      histopathological findings, the IVCM results (cell morphology, cytoplasm and
      nucleus) of OSSN were analyzed. The difference analysis between the count data of
      two groups was carried out by the chi square test or Fisher's exact test.
      Receiver operating characteristic curve and area under the curve (AUC) were used
      to describe the accuracy of each parameter to differentiate SCC from OSSN.
      Results: There were 12 males and 11 females among the 23 patients aged (62+/-15)
      years. With the histopathological diagnosis, there were 15 cases (15 eyes) in the
      CIN group and 8 cases (8 eyes) in the SCC group. Eye redness, pain, foreign body
      sensation and tears were the symptoms of OSSN. There was no significant
      difference in clinical symptoms between the CIN and SCC groups. The size of
      tumors and the incidence of trophoblastic vessels in the SCC group were greater
      than those in the CIN group [8.5(6.5-15.5) mm vs. 5.8(4.0-8.5)mm,
      Z=4.702,P=0.029; 7/8 vs. 5/15, chi2=6.135, P=0.013). In histopathology,
      multilayered epithelia with cellular polymorphism, varied cytoplasm staining, and
      slightly thicker nuclei were observed in the CIN group. The corneal epithelial
      cells of SCC patients were markedly heterogeneous, and the intercellular bridge
      structure can be detected. Proliferative cells appeared with spindle shaped
      cells, nuclear mitotic figures and syncytial cells in the SCC group. The IVCM
      examination in the CIN group and SCC group showed that the cytoplasm was high and
      the ratio of nuclear plasma increased. There was no significant difference
      between the two groups in the size of epithelial cells, cytoplasm reflectivity,
      and nuclear cytoplasm ratio (P=0.053, 0.108, 0.067). The proportions of nuclear
      mitotic figures, spindle or chimeric cells, nests of whirlpool cells and the
      abnormal cells of the superficial stroma layer (8/8, 8/8, 8/8 and 8/8) in the SCC
      group was higher than those (2/15, 1/15, 4/15 and 0/15) in the CIN group, and the
      difference was statistically significant (P=0.001, 0.001, 0.003; P<0.001). Among
      these IVCM parameters, the abnormal cells of the superficial stroma layer had the
      highest diagnostic ability with the AUC value of 1.000, and the following AUC
      values were 0.933 for mitotic or double nuclei, 0.901 for spindle or chimeric
      cells, and 0.867 for the nests of whirlpool cells. Conclusions: The IVCM
      characteristics of OSSN are the dysplastic cells, hyper-reflective cytoplasm and
      increased nuclear plasma ratio in the corneal epithelium. Dysplastic cells
      appearing in the superficial stroma layer, nuclear mitotic figures and nests of
      vortex cells are the main IVCM parameters to support the malignant change of OSSN
      lesions. (Chin J Ophthalmol, 2018, 54: 652-660).

PMID- 30220180
TI  - [Clinicopathological study on conjunctival osseous choristoma].
AB  - Objective: To summarize the clinical pathologic characteristics of conjunctival
      osseous choristoma. Methods: Retrospective case series study. Six cases of
      conjunctival osseous choristoma between January 2009 and June 2016 from Tianjin
      Eye Hosptial were reviewed retrospectively. The clinical features, CT
      characteristics and histological characteristics were analyzed. Results: The 6
      cases includes 3 male patients and 3 females. The age of the patients ranged from
      4 to 20 years. Three cases involved with the right eye and the other 3 involved
      with the left eye. Major clinical feature of the patient is the flat uplift tumor
      in the superior temporal quadrant of the conjunctiva. CT features of conjunctival
      osseous choristoma revealed a oval calcium spot of eyeball surface. All the
      patients received surgery. Pathological examination showed that the tumor is
      composed of bone tissue which was surrounded by fibrous tissue, and Haversian
      canals are present in compact bone tissue. Five patients were followed for 23
      months to 8 years. None of the patients relapsed after operation. Conclusions:
      The major feature of conjuncital osseous choristoma is a tumor in the superior
      temporal quadrant of conjunctiva. Imaging examination reveals a oval calcium spot
      of eyeball surface. Pathological examination reveals that the osseous tumor is
      composed of compact bone tissue which was surrounded by fibrous tissue.Haversian
      canals are present in compact bone tissue.Diagnosis is dependent on
      histopathological examination. It is not prone to relapse after complete
      resection surgery. (Chin J Ophthalmol, 2018, 54: 661-664).

PMID- 30220181
TI  - [Clinical analysis of orbital ectopic meningiomas].
AB  - Objective: To investigate the clinical features, imaging features, diagnoses and
      therapeutic regimens of orbital ectopic meningiomas. Methods: A retrospective
      study. All the clinical data of 10 patients (10 eyes) with orbital ectopic
      meningiomas were analyzed retrospectively from August 1999 to October 2016. They
      included imaging data such as color Doppler ultrasound, CT and MRI, and
      information of diagnosis, pathology, therapeutic regimen and prognosis. Results:
      The age of orbital ectopic meningiomas was 7 to 68 years old. There were 4 males
      and 6 females. The clinical manifestations were mainly with swollen eyelid (8
      cases), exophthalmos (7 cases), visual impairment (2 cases) and accidentally
      found a mass in the orbit with physical examination(2 cases). The tumor was
      located in (5 cases) or outside (5 cases) the muscular funnel of the orbit. The
      imaging features of CT included the irregular shape, unclear border, and
      extraocular muscular adhesions (10 cases). T1 weighted image of MRI showed low
      and medium signals and T2 weighted image showed medium and high signals(8 cases).
      There was no definite diagnosis before surgery. Ten patients were treated with
      surgery, and it was confirmed intraoperatively that the tumors were not adjacent
      to the optic nerve and orbital periosteum. The pathological diagnoses were mostly
      epithelial meningiomas (9 cases). There were no significant changes in visual
      acuity, but temporary eye movement disorders occurred postoperatively (10 cases).
      The patients were followed for 6 months to 6 years. Two cases underwent recurrent
      at 3 months and 2 years after operation, and received treatment of gamma-knife
      radiation therapy. The tumor reduced after gamma-knife radiotherapy, and had no
      change in 2 years and 6 years, respectively. Conclusions: As a kind of rare
      orbital tumors, it is difficult to diagnose orbital ectopic meningiomas
      accurately. The clinical features and imaging findings can help to detect the
      disease, but lacking the characteristics of optic nerve sheath meningiomas and
      periosteal meningiomas. Surgical resection could achieve a good prognosis without
      visual impairment. If the tumor recurs after pathological diagnosis, gamma-knife
      conformal radiation therapy may still be effective for tumor recurrence. (Chin J
      Ophthalmol, 2018, 54: 665-670).

PMID- 30220182
TI  - [Pathological features of levator aponeurosis in patients with involutional
      blepharoptosis].
AB  - Objective: To observe pathological features of levator aponeurosis in patients
      with involutional ptosis. Methods: A prospective study. Twenty-nine consecutive
      patients with involutional blepharoptosis who underwent levator aponeurosis
      advancement surgery for blepharoptosis correction were enrolled at Beijing
      Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University from
      2007 to 2013. Twenty-nine specimens of the levator aponeurosis were obtained
      during surgery. Hematoxylin-eosin staining, Van Gieson staining, Masson staining,
      immunohistochemistry and transmission electron microscope observations were
      performed to observe the features of levator aponeurosis. Twelve normal specimens
      of fresh levator aponeurosis were obtained from Beijign Tongren Eyebank as
      control group. Mann-Whitney's U-test and multiple linear regression were used for
      statistical analysis. Results: Among the enrolled cases, there were 19 males and
      10 females;14 cases were diagnosed with moderate ptosis and 15 cases with severe
      ptosis;9 cases involved with both eyes, 9 cases with right eyes, and 11 cases
      with left eyes. The mean age was 59 years. Among the 12 normal cases, there were
      5 males and 7 females. The mean age was 56 years. Histopathological observation
      showed fascicle disruption(+++, ++, + 24, 2, 3 vs. 0, Z=-5.666, P<0.001),
      scarcity of cross-striations(+++, ++, + 23, 2, 4 vs. 0, Z=-5.582,P<0.001),
      collagen fibers hyperplasia(+++, ++, + 15, 10, 4 vs. 0, Z=-5.223,P<0.001), fatty
      infiltration(+++, ++, + 24, 5, 0 vs. 0, Z=-5.671,P<0.001), and a decrease of
      myoglobin expression(+++,++,+,- 9, 1, 1, 15 vs. 8, 1, 0, 0, Z=-3.004, P=0.005) in
      levator aponeurosis. Transmission electron microscope recorded presence of
      collagen fiber hyperplasia and cellular degeneration including mitochondria
      swelling and hyperplasia, vacuoles, lipid droplets, nucleus pycnosis, chromosome
      condensation, disintegrated organelles, myeloid body and autophagy. Multivariate
      linear regression showed a correlation between fat infiltration and
      age(beta=0.425, P=0.043) while suspicious related clinical features as
      independent variables and observed histopathological features as dependent
      variables. Conclusion: The levator aponeurosis appears to be involved with muscle
      fiber degeneration, collagen fiber hyperplasia and cellular degeneration in
      patients with involutional blepharoptosis. (Chin J Ophthalmol, 2018, 54: 671
      677).

PMID- 30220183
TI  - [Comparison of swept source anterior segment optical coherence tomography and
      ultrasound biomicroscopy in measurement of anterior chamber depth and anterior
      chamber angle data in age-related cataract patients].
AB  - Objective: To explore the difference and agreement in the measurement of anterior
      chamber depth (ACD) and anterior chamber angle data in age-related cataract
      patients between swept source anterior segment optical coherence tomography (SS
      AS-OCT) and ultrasound biomicroscopy (UBM). Methods: A prospective study. Forty
      five eyes from 45 age-related cataract patients were selected at Beijing Tongren
      Eye Center, Beijing Tongren Hospital, Capital Medical University from November to
      December 2016. There were 23 males and 22 females aged (51+/-19) years. SS-AS-OCT
      and UBM were used to measure the ACD, angle opening distance (AOD 500) and
      trabecular-iris angle (TIA 500). The paired samples t-test and Pearson linear
      correlation were used for statistical analysis, and the Bland-Altman analysis was
      used to evaluate the measurement consistency of the two tools. Results: The ACD
      measured by SS-AS-OCT and UBM was (2.750+/-0.544) mm and (2.775+/-0.531) mm,
      respectively, the difference was statistically significant (t=2.109, P=0.040),
      and the measurement results were positively correlated (r=0.989, P<0.001). In the
      nasal, temporal, upper and lower positions, the AOD 500 and TIA 500 values
      measured by SS-AS-OCT and UBM had a significant difference [AOD 500: (0.451+/
      0.201) mm vs.(0.421+/-0.194) mm, (0.499+/-0.229) mm vs. (0.465+/-0.207) mm,
      (0.390+/-0.215) mm vs. (0.355+/-0.208) mm, (0.441+/-0.226) mm vs. (0.423+/-0.215)
      mm, t=4.262, 4.350, 5.355, 4.415; TIA 500: 39.587 degrees +/-14.698 degrees vs.
      36.944 degrees +/-13.790 degrees , 42.149 degrees +/-14.138 degrees vs. 40.289
      degrees +/-13.041 degrees , 36.482 degrees +/-15.887 degrees vs. 35.600 degrees
      +/-15.215 degrees , 38.504 degrees +/-14.805 degrees vs. 36.818 degrees +/-14.931
      degrees , t=5.131, 4.658, 4.174, 5.731; all P<0.001] and a significant linear
      correlation (AOD 500: r=0.971, 0.975, 0.979, 0.973; TIA 500: r=0.972, 0.957,
      0.956, 0.970; all P<0.001). The Bland-Altman method showed that the two
      modalities had comparable results for the ACD, AOD 500 and TIA 500 (2.22%-6.67%
      of the measured value outside the 95% consistency boundaries). Conclusion: SS-OCT
      and UBM show a good agreement in the measurement of ACD and anterior chamber
      angle data in age-related cataract patients, though there is difference between
      them in measurement results. (Chin J Ophthalmol, 2018, 54: 678-682).

PMID- 30220184
TI  - [Correlation between ultrasonographic optic nerve sheath diameter and
      intracranial pressure].
AB  - Objective: To evaluate the association of the ultrasonographic optic nerve sheath
      diameter (ONSD) and intracranial pressure (ICP), and the feasibility of
      ultrasonographic ONSD in predicting high ICP. Methods: A prospective study. The
      outpatients who planned to measure ICP by lumbar puncture in Department of
      Neurology, Xuanwu Hospital, Capital Medical University were selected from January
      2011 to May 2012. All the retrobulbar ONSD measurement with B-scan ultrasound was
      performed just before lumbar puncture. When high ICP was defined as ICP more than
      200 mmH2O(1 mmH2O=0.009 8 kPa), the participants were divided into the high ICP
      group and the normal ICP group. The Pearson correlation coefficient analysis was
      used to analyze the correlation between ICP and postbulbar ONSD measurements. The
      difference in ONSD was compared between the high ICP and normal ICP groups with
      the t test. The receiver operating characteristic (ROC) curve was used to
      calculate the cutoff value of mean ONSD and evaluate the sensitivity and
      specificity of the method. Results: A total of 130 participants were involved in
      this study. There were 71 males and 59 females, aged (38+/-14) years.The mean ICP
      was (209.84+/-79.99) mmH2O. The mean ONSD was (5.68+/-0.78) mm in the right eyes,
      (5.78+/-0.78) mm in the left eyes, and (5.73+/-0.71) mm in both eyes. The ICP had
      a significant correlation with ONSD in the right eyes (r=0.54, P<0.001), ONSD in
      the left eyes (r=0.56, P<0.001) and ONSD in both eyes (r=0.60, P<0.001), but no
      correlation with age (r=-0.14, P=0.114) and gender (r=0.20, P=0.817). The ONSD in
      the high ICP group (n=65) was (6.11+/-0.66) mm, (6.22+/-0.56) mm and (6.17+/
      0.50) mm in the right eyes, left eyes, and both eyes, respectively. Compared with
      the ONSD in the normal ICP group (n=65), which was (5.26+/-0.64) mm in the right
      eyes, (5.34+/-0.72) mm in the left eyes and (5.30+/-0.62) mm in both eyes, there
      was a significantly enlarged ONSD in the high ICP group (t=-7.507, -7.778, 
      8.779, all P<0.001). The ROC analysis showed the ONSD of 5.6 mm was the best
      cutoff value with a sensitivity of 86% and a specificity of 71% for identifying
      high ICP. Conclusions: There is a significantly positive correlation between ICP
      and postbulbar ONSD measured by ultrasound. This non-invasive method may be an
      alternative approach to predicting the ICP value of patients whose ICP
      measurement via lumbar puncture is at high risk. However, it can not replace the
      direct ICP measurement with the invasive method. (Chin J Ophthalmol, 2018, 54:
      683-687).

PMID- 30220186
TI  - [Complications and status quo of plaque radiotherapy for uveal melanoma].
AB  - Radiation treatment, including episcleral plaque radiotherapy, stereotactic
      radiosurgery, proton beam therapy and so on, is the primary eye-conserving choice
      for uveal melanoma. But the complications resulted from radiotherapy's
      nonselective kill to tumor cells can be visual-threatening and eventually result
      in the enucleation of eyeball. This review summarizes current radiation
      strategies for uveal melanoma and how these complications occur, develop and
      present, in the hope that it could provide insights for the radiation
      interventions and diagnosis of radiative complications. (Chin J Ophthalmol, 2018,
      54: 707-711).

PMID- 30220185
TI  - [A study on observing the central macular choroidal thickness of thyroid
      associated ophthalmopathy patients with spectral-domain optical coherence
      tomography].
AB  - Objective: To compare the differences in the central macular choroidal thickness
      (CMCT) between thyroid-associated ophthalmopathy (TAO) patients in active and
      inactive stages, and the healthy subjects used spectral-domain optical coherence
      tomography (SD-OCT) and assess the potential of using CMCT as an indicator for
      follow-up of TAO patients. Methods: Cross-sectional study. Eleven active stage
      TAO patients (22 eyes, active TAO group) and 21 inactive stage TAO patients (42
      eyes, inactive TAO group) who received treatment at the Department of
      Ophthalmology, First People's Hospital of Nantong during January 2015 and
      December 2017 were enrolled. Twenty-three healthy subjects (46 eyes) with
      comparable ages to the two TAO groups were enrolled in the healthy control group.
      TAO activity was assessed using the TAO clinical activity score (CAS) system. All
      subjects underwent best corrected visual acuity, slit lamp examination, Goldmann
      tonometer for intraocular pressure measurement, direct ophthalmoscopy, A
      superelocular measurement, ocular protrusion measurement, and SD-OCT detection of
      CMCT. The variance analysis was used to compare the differences of intraocular
      pressure, eyeball protrusion and CMCT between the three groups. The correlation
      between CMCT and various clinical indicators was analyzed by univariate linear
      regression analysis and multivariate linear regression analysis. Results: The
      intraocular pressure and eyeball protrusion indicators of the active TAO group,
      the inactive TAO group, and the control group were (20.16+/-3.49) mmHg (1
      mmHg=0.133 kPa) and (18.68+/-1.64) mm, (15.42+/-2.49) mmHg and (15.64+/-1.01) mm,
      (15.72+/-2.38) mmHg and (12.02+/-0.83) mm, respectively. The intraocular pressure
      and ocular protrusion of the active TAO group were higher than those of the
      inactive TAO group and the healthy control group, the differences between the
      groups are of statistical significance (all P<0.001). The CMCT value of the
      active TAO group, the inactive TAO group and the healthy control group were
      (391.27+/-33.89) MUm, (317.31+/-29.62) MUm, and (304.26+/-42.26) MUm,
      respectively. The CMCT of the active TAO group was significantly higher than the
      inactive group and the healthy control group, the differences between the groups
      are of statistical significance (all P<0.001). Based on univariate analysis,
      thicker CMCT was significantly associated with intraocular pressure (t=4.600,
      P<0.001); after correction of intraocular pressure, thicker CMCT was
      significantly associated with CAS (beta=0.848, 95%CI 15.608-21.499, P<0.001).
      Multivariate analysis showed a correlation between thicker CMCT and CAS scores
      (P<0.001), thyroid function (P<0.001), and intraocular pressure(P=0.039).
      Conclusions: The CMCT in the eyes of active TAO patients is higher than that of
      the inactive TAO patients and healthy people. The CMCT examination is of
      referential value, and may be used as a tool for assessing the activity of
      lesions in patients with TAO and clinical follow-up. (Chin J Ophthalmol, 2018,
      54: 688-693).

PMID- 30220187
TI  - [Experimental research on mesenchymal stem cells (MSCs) therapy for autoimmune
      uveitis].
AB  - Autoimmune uveitis is a major cause of visual disability. Treatment of chronic
      and recurrent uveitis can be extremely difficult, as various complications of it
      could impede the long-term usage of corticosteroids and immunosuppressants.
      Mesenchymal stem cells are of both immunosuppressive and neurotrophic effect, and
      can enhance the antimicrobial ability of the body, thereby hold great promise in
      clinical application for treating uveitis. (Chin J Ophthalmol, 2018, 54: 712
      715).

PMID- 30220188
TI  - [Effect of anatomic features of ciliary body on primary angle closure].
AB  - The mechanisms of primary angle closure are complex and varied. It is well known
      that the anatomic features of iris and lens may have influence on the presence of
      angle closure. However, the effect of structural features of ciliary body on
      primary angle closure remain unclear yet. The anterior situation of ciliary
      processes was extensively proved to be one of the predisposing factors of angle
      closure. While it's still controversial how the thickness of ciliary body may
      affect angle closure. Recent researches found that primary angle closure was
      associated with thinner ciliary body thickness. This review is aimed at
      introducing current researches of the effects of ciliary processes position and
      ciliary body thickness on primary angle closure. (Chin J Ophthalmol, 2018, 54:
      716-720).

PMID- 30220189
TI  - Enhancement of Expression Level of Modified t-PA (TNKase) in Leishmania
      tarentolae by Induction System
AB  - Background: The expression of bio-therapeutic proteins in mammalian cells, such
      as CHO, attains high homogeneity related to post-translational modifications.
      Although CHO remains the most popular cell line for bestselling biotherapeutic
      proteins on the market, there are still drawbacks such as expensive culture
      media, long time line, and high drug cost. Recently, researches on a novel
      Leishmania protozoan system have confirmed that this low level eukaryote could
      represent a competitive alternative to the mammalian cell lines. Methods: The
      full length of coding sequence of modified tPA TNKase tenecteplase) was
      synthesized and cloned into an inducible expression vector of L. tarentolae T7-TR
      cells. Results: The expression of the construct was driven by a Tet-inducible
      promoter. A Leishmania secretory signal sequence was also added to the expression
      cassette to facilitate the release of the recombinant protein into the medium.
      The secretory recombinant protein was analyzed and confirmed by SDS-PAGE and
      Western blot analyses. The expression level of TNKase in this novel system of L.
      tarentolae was 810 IU/mL after induction, which means that the percentage of
      expression increases two times compared to previous models in L. tarentolae. The
      TNKase activity was comparable with Activase. Conclusion: Our results suggested
      that expressed TNK (modified tPA) is functionally compatible with Activase
      regarding their effect on fibrinolysis. Given the post-translational modification
      similarities between mammalian and L. tarentolae, it is speculated that this
      system is capable of producing complex proteins such as tPA similar to mammalian
      system, with easier manipulation and non-expensive method.

PMID- 30220190
TI  - Immunohistochemical Expression of Nanog and Its Relation with Clinicopathologic
      Characteristics in Breast Ductal Carcinoma
AB  - Background: Cancer stem cells (CSCs) are a group of tumor cells with self-renewal
      property and differentiation potential. CSCs play a crucial role in malignant
      progression of several types of tumors. However, what is still controversial is
      the clinicopathological relationship between Nanog marker and its prognostic
      value in the patients with breast cancer. The expression of Nanog in the patients
      with breast cancer and its correlation with clinicopathological prognostic
      factors was explored in the present study. Methods: A sample of 120 breast cancer
      tissues was obtained from the patients who referred to Imam Khomeini Hospital in
      Sari city, Iran during January 2012 and December 2016. The associations between
      Nanog expression and clinicopathological factors were analyzed based on
      immunohistochemical analysis. Results: It was found that 67 (55.8%) patients had
      Nanog expression, and high expression rate was observed in 24 (36%) cases
      (staining index >=3). Moreover, there was a statistically significant
      relationship between Nanog expression and clinicopathological factors, including
      tumor grade (p = 0.001), lymph node metastasis (p = 0.01), and the stage of the
      disease (p = 0.003). Conclusion: Findings of the study indicate that Nanog is a
      biomarker for prognostic prediction in patients with breast cancer. However,
      further studies of Nanog are suggested to provide novel therapeutic targets for
      curing breast cancer.

PMID- 30220191
TI  - Influence of Deuterium-Depleted Water on the Isotope D/H Composition of Liver
      Tissue and Morphological Development of Rats at Different Periods of Ontogenesis
AB  - Background: This study aimed to evaluate the reaction of organism of laboratory
      animals on deuterium-depleted drinking diet. To assess the cell energy
      metabolism, the effect of a liquid medium with different deuterium contents on
      isolated liver mitochondria of random bred rats and Wistar rats was studied.
      Methods: This experimental study on the effect of deuterium-depleted drinking
      water (DDW) on 16-week-old male Wistar rats lasted for four weeks. Energy
      metabolism of mitochondria was examined through the production of hydrogen
      peroxide using an Amplex(r) Red Hydrogen Peroxide/Peroxidase Assay Kit. Results:
      Modification of isotope (deuterium-protium [D/H]) composition of rats' blood and
      organ tissues with DDW (-7050/00), introduced into rats' diet within four weeks,
      leads to the formation of isotope D/H gradient between blood plasma and organ
      tissues and affects isotope D/H exchange reactions on the adaptive processes. The
      isolated liver mitochondria from the random bred rats consumed DDW presented a
      maximum increase in H2O2 production during the incubation in DDW medium. This
      increased level of H2O2 production was higher than that of the isolated liver
      mitochondria of the rats consuming natural deuterium content drinking water (
      240/00). Conclusion: The obtained results indicate the possibility of nutritional
      correction of isotope D/H metabolism in the blood by means of products with
      modified isotope composition, as well as the prospects of using isotope exchange
      reactions in case of imbalance in function of the body's defense systems in
      different generations of animals.

PMID- 30220192
TI  - Application of a non-parametric non-mixture cure rate model for analyzing the
      survival of patients with colorectal cancer in Iran.
AB  - OBJECTIVES: Colorectal cancer (CRC) patients are considered to have been cured
      when the mortality rate of individuals with the disease returns to the same level
      as expected in the general population. This study aimed to assess the impact of
      various risk factors on the cure fraction of CRC patients using a real dataset of
      Iranian CRC patients with a non-mixture non-parametric cure model. METHODS: This
      study was conducted on the medical records of 512 patients who were definitively
      diagnosed with CRC at Taleghani Hospital, Tehran, Iran from 2001 to 2007. A non
      mixture non-parametric cure rate model was applied to the data after using
      stepwise selection to identify the risk factors of CRC. RESULTS: For non-cured
      cases, the mean survival time was 1,243.83 days (95% confidence interval [CI],
      1,174.65 to 1,313.00) and the median survival time was 1,493.00 days (95% CI,
      1,398.67 to 1,587.33). The 1- and 3-year survival rates were 92.9% (95% CI, 91.0
      to 95.0) and 73.4% (95% CI, 68.0 to 79.0), respectively. Pathologic stage T1 of
      the primary tumor (estimate=0.58; p=0.013), a poorly differentiated tumor
      (estimate=1.17; p<0.001), a body mass index (BMI) between 18.6 and 24.9 kg/m2
      (estimate=-0.60; p=0.04), and a BMI between 25.0 and 29.9 kg/m2 (estimate=-1.43;
      p<0.001) had significant impacts on the cure fraction of CRC in the multivariate
      analysis. The proportion of cured patients was 64.1% (95% CI, 56.7 to 72.4).
      CONCLUSIONS: This study found that the pathologic stage of the primary tumor,
      tumor grade, and BMI were potential risk factors that had an impact on the cure
      fraction. A non-mixture non-parametric cure rate model provides a flexible
      framework for accurately determining the impact of risk factors on the long-term
      survival of patients with CRC.

PMID- 30220193
TI  - Current status of newborn hearing screening in low-income families in the
      southeastern region of Korea.
AB  - OBJECTIVES: The aim of this study was to analyze the current status and problems
      of hearing screening tests for newborns in low-income families in the
      southeastern Korea. METHODS: This study analyzed data from the Ministry of Health
      and Welfare's project on the early detection of hearing loss in newborns in low
      income families in the southeastern Korea (2011-2015). RESULTS: The referral rate
      was 1.33, 1.69, and 1.27% in Daegu, Gyeongbuk, and Ulsan, respectively. The
      confirmatory test rate was 36.09, 23.38, and 52.94% in Daegu, Gyeongbuk, and
      Ulsan, respectively. The incidence of hearing loss (adjusted) was 0.41, 0.62, and
      0.41% in Daegu, Gyeongbuk, and Ulsan, respectively. After confirming hearing
      loss, newborns with hearing handicaps were mostly lost to follow-up, and
      rehabilitation methods, such as hearing aids or cochlear implants, were not used.
      The screening tests were performed within 1 month of birth, and the confirmatory
      tests were generally performed within 3 months of birth. However, more than 3
      months passed before the confirmatory tests were performed in infants with risk
      factors for hearing loss in Gyeongbuk and Ulsan. CONCLUSIONS: Hearing screening
      tests were conducted in newborns from low-income families in southeastern Korea
      who received a coupon for free testing, but the newborns that were referred after
      the screening tests were not promptly linked to the hospitals where confirmatory
      tests were performed. Furthermore, hearing rehabilitation was not consistently
      performed after hearing loss was confirmed. To successful early hearing loss
      detection and intervention, a systematic tracking system of hearing loss children
      is needed.

PMID- 30220194
TI  - Drug-Loaded Halloysite Nanotube-Reinforced Electrospun Alginate-Based Nanofibrous
      Scaffolds with Sustained Antimicrobial Protection.
AB  - Halloysite nanotube (HNT)-reinforced alginate-based nanofibrous scaffolds were
      successfully fabricated by electrospinning to mimic the natural extracellular
      matrix (ECM) structure which is beneficial for tissue regeneration. An antiseptic
      drug, cephalexin (CEF)-loaded HNT, was incorporated into the alginate-based
      matrix to obtain sustained antimicrobial protection and robust mechanical
      properties, the key criteria for tissue engineering applications. Electron
      microscopic imaging and drug release studies revealed that CEF had penetrated
      into the lumen space of the HNT and also deposited on the outer walls, with a
      total loading capacity of 30 wt %. Moreover, the diameter of alginate-based
      nanofibers of the scaffolds ranged from 40 to 522 nm with well-aligned HNTs,
      resulting in superior mechanical properties. For instance, the addition of 5%
      (w/w) HNT improved the tensile strength (sigma) and elastic modulus by 3-fold and
      2-fold, respectively, compared to those of the alginate-based scaffolds without
      HNT. The fabricated scaffolds exhibited remarkable antimicrobial properties
      against both Gram-negative and Gram-positive bacteria, and the cytotoxicity
      studies confirmed the nontoxicity of the fabricated scaffolds. Drug release
      kinetics showed that CEF inside HNTs diffuses within 24 h and that the diffusion
      of the drug is delayed by 7 days once the CEF-loaded HNTs are incorporated into
      the alginate-based nanofibers. These fabricated alginate-based electrospun
      scaffolds with enhanced mechanical properties and sustained antimicrobial
      protection hold great potential to be used as artificial ECM scaffolds for tissue
      engineering applications.

PMID- 30220195
TI  - Metal-Organic Framework-Derived Co3O4/Au Heterostructure as a Catalyst for
      Efficient Oxygen Reduction.
AB  - Porous nanostructures with a yolk-shell complex interior will provide lots of
      virtues to construct advanced catalysts. In our work, the preparation of novel
      yolk-shell Au nanocrystal-loaded Co3O4 nanocages (Co3O4/Au heterostructure) from
      a metal-organic framework-derived composite was reported. Scanning electron
      microscopy, energy-dispersive X-ray spectroscopy, transmission electron
      microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Brunauer-Emmett
      Teller analysis, and so forth were used to analyze the morphology, structure, and
      composition of the heterostructures. Most importantly, Co3O4/Au heterostructures
      are a kind of low-cost, good performance catalysts for the oxygen reduction
      reaction to replace the noble-Pt catalysts. The high surface area of the porous
      structure and the excellent electron transfer properties of well-dispersed Au
      nanocrystals and also the electronic coupling effect between Co3O4 and Au in the
      composites are attributed to the good performance.

PMID- 30220196
TI  - Photosensitizing Metal-Organic Layers for Efficient Sunlight-Driven Carbon
      Dioxide Reduction.
AB  - Metal-organic layers (MOLs), a free-standing monolayer version of two-dimensional
      metal-organic frameworks (MOFs), have emerged as a new class of 2D materials for
      many potential applications. Here we report the design of a new photosensitizing
      MOL, Hf12-Ru, based on Hf12 secondary building units (SBUs) and [Ru(bpy)3]2+ (bpy
      = 2,2'-bipyridine) derived dicarboxylate ligands. After modifying the SBU surface
      of Hf12-Ru with M(bpy)(CO)3X (M = Re and X = Cl or M = Mn and X = Br) derived
      capping molecules through carboxylate exchange reactions, the resultant Hf12-Ru
      Re and Hf12-Ru-Mn MOLs possess both [Ru(bpy)3]2+ photosensitizers and
      M(bpy)(CO)3X catalysts for efficient photocatalytic CO2 reduction. The proximity
      of the MOL skeleton to the capping ligands (1-2 nm) facilitates electron transfer
      from the reduced photosensitizer [Ru(bpy)3]+ to MI(bpy)(CO)3X (M = Re, Mn)
      catalytic centers, resulting in CO2 reduction turnover numbers of 8613 under
      artificial visible light and of 670 under sunlight. MOLs thus represent a novel
      platform to assemble multifunctional materials for studying artificial
      photosynthesis.

PMID- 30220197
TI  - Platinum Nanozyme-Catalyzed Gas Generation for Pressure-Based Bioassay Using
      Polyaniline Nanowires-Functionalized Graphene Oxide Framework.
AB  - Pressure-based bioassays incorporating biomolecular recognition with a catalyzed
      gas-generation reaction have been developed for gas biosensors, but most involve
      poor sensitivity and are unsuitable for routine use. Herein we design an
      innovative gas pressure-based biosensing platform for the detection of Kanamycin
      (Kana) on polyaniline nanowires-functionalized reduced graphene oxide (PANI/rGO)
      framework by using platinum nanozyme-catalyzed gas generation. The signal was
      amplified by coupling with catalytic hairpin assembly (CHA) and strand
      displacement amplification (SDA). Upon target Kana introduction, the analyte
      initially triggered a SDA reaction between hairpin DNA1 and hairpin DNA2, and
      then induced CHA conjugation between magnetic bead-labeled hairpin DNA3 (MB-H3)
      and platinum nanoparticle-labeled hairpin DNA4 (Pt-H4) to form a three
      dimensional network. Numerous platinum nanoparticles (peroxidase-like nanozymes)
      were carried over with magnetic beads to reduce hydrogen peroxide into oxygen.
      The as-produced gas compressed PANI/rGO frameworks (modified to polyurethane
      sponge, used as the piezoelectric materials) in a homemade pressure-tight device,
      thus causing the increasing current of PANI/rGO sponge thanks to its deformation.
      The change in the current caused by the as-generated gas pressure was determined
      on an electrochemical workstation. Under optimum conditions, PANI/rGO sponge
      exhibited outstanding compressibility, stable signal-waveform output, fast
      response and recovery time (~109 ms), and the current increased with the
      increasing Kana concentration within a dynamic working range of 0.2-50 pM at a
      detection limit of 0.063 pM. Good reproducibility, specificity, and acceptable
      precision were acquired for Kana analysis. In addition, the accuracy of this
      method was monitored to evaluate real milk samples with the well-matched results
      obtained by using the referenced Kana ELISA kit.

PMID- 30220198
TI  - Evaluation of a New Reagent-Ion Source and Focusing Ion-Molecule Reactor for Use
      in Proton-Transfer-Reaction Mass Spectrometry.
AB  - We evaluate the performance of a new chemical ionization source called Vocus,
      consisting of a discharge reagent-ion source and focusing ion-molecule reactor
      (FIMR) for use in proton-transfer-reaction time-of-flight mass spectrometry (PTR
      TOF) measurements of volatile organic compounds (VOCs) in air. The reagent ion
      source uses a low-pressure discharge. The FIMR consists of a glass tube with a
      resistive coating, mounted inside a radio frequency (RF) quadrupole. The axial
      electric field is used to enhance ion collision energies and limit cluster ion
      formation. The RF field focuses ions to the central axis of the reactor and
      improves the detection efficiency of product ions. Ion trajectory calculations
      demonstrate the mass-dependent focusing of ions and enhancement of the ion
      collision energy by the RF field, in particular for the lighter ions. Product ion
      signals are increased by a factor of 10 when the RF field is applied (5000-18 000
      cps ppbv-1), improving measurement precision and detection limits while operating
      at very similar reaction conditions as traditional PTR instruments. Because of
      the high water mixing ratio in the FIMR, we observe no dependence of the
      sensitivity on ambient sample humidity. In this work, the Vocus is interfaced to
      a TOF mass analyzer with a mass resolving power up to 12 000, which allows clear
      separation of isobaric ions, observed at nearly every nominal mass when measuring
      ambient air. Measurement response times are determined for a range of ketones
      with saturation vapor concentrations down to 5 * 104 MUg m-3 and compare
      favorably with previously published results for a PTR-MS instrument.

PMID- 30220199
TI  - Molecular Quadripod as a Noncovalent Interfacial Coupling Reagent for Forming
      Immobilized Coordination Assemblies.
AB  - A pyrene-cored molecular quadripod 1,3,6,8-tetra(di( p-pyrid-4
      ylphenyl)amino)pyrene (TAPyr) is presented as a noncovalent interfacial coupling
      reagent for the immobilization of coordination assemblies. This bench-stable
      molecule is readily available and has a quadripod shape with four pyridine legs
      and four pyridine handles on the top exterior. By a simple and short dipping
      procedure under ambient conditions, TAPyr is firmly immobilized on electrode
      surfaces in an upright fashion as probed by electrochemical, absorption spectral,
      atomic force microscopy, and scanning tunneling microscopy analysis. Using
      Pd(PhCN)2Cl2 as a metallolinker, 4-ferrocenylpyridine, a pyridine-terminated
      monoruthenium complex 1, and a diruthenium complex 2 with two pyridine ends have
      been grafted onto the ITO/TAPyr surface. The obtained thin films exhibit good
      electrochemical stability that is comparable or superior to those prepared by the
      state-of-the-art Si-O-Sn covalent functionalization. Appealing electrochromism is
      demonstrated with the thin films of ruthenium complexes on ITO.

PMID- 30220200
TI  - Synthesis of Colloidal Pd/Au Dilute Alloy Nanocrystals and Their Potential for
      Selective Catalytic Oxidations.
AB  - Selective oxidations are crucial for the creation of valuable chemical building
      blocks but often require expensive and unstable stoichiometric oxidants such as
      hydroperoxides and peracids. To date, many catalysts that contain a single type
      of active site have not been able to attain the desired level of selectivity for
      partially oxidized products over total combustion. However, catalysts containing
      multiple types of active sites have proven to be successful for selective
      reactions. One category of such catalysts is bimetallic alloys, in which
      catalytic activity and selectivity can be tuned by modifying the surface
      composition. Traditional catalyst synthesis methods using impregnation struggle
      to create catalysts with sufficient control over surface chemistry to accurately
      tune the ensemble size of the desired active sites. Here we describe the
      synthesis of colloidal nanocrystals of dilute alloys of palladium and gold. We
      show that when supported on titania (TiO2), tuning the composition of the Pd/Au
      nanocrystal surface provides a synergistic effect in the selective oxidation of 2
      propanol to acetone in the presence of H2 and O2. In particular, we show that
      certain Pd/Au surface ratios exhibit activity and selectivity far superior to Pd
      or Au individually. Through precise structural characterization we demonstrate
      that isolated atoms of Pd exist in the most active catalysts. The synergy between
      isolated Pd atoms and Au allows for the formation of reactive oxidizing species,
      likely hydroperoxide groups, responsible for selective oxidation while limiting
      oxygen dissociation and, thus, complete combustion. This work opens the way to
      more efficient utilization of scarce noble metals and new options for catalyzed
      selective oxidations.

PMID- 30220201
TI  - Improved Method for Isolation and Purification of Underivatized Amino Acids for
      Radiocarbon Analysis.
AB  - We have improved a method for isolation and purification of individual amino
      acids for compound-specific radiocarbon analysis (CSRA). To remove high
      performance liquid chromatography (HPLC) eluent blanks from isolated amino acid
      fractions prior to the radiocarbon (Delta14C) measurement, each fraction was
      filtered through a membrane filter and then washed with diethyl ether twice.
      Radiocarbon measurements on standard amino acids processed and purified with the
      above method using elemental analyzer-accelerator mass spectrometry resulted in
      Delta14C values that were in strong agreement ( R2 = 0.998) with the original
      Delta14C value of each amino acid standard. From these measurements, we calculate
      dead and modern carbon contamination contributions as 1.2 +/- 0.2 and 0.3 +/- 0.1
      MUgC, respectively, which are consistent with direct assessments of HPLC
      procedural blanks of 1.0 +/- 0.8 MUgC per sample. These contamination constraints
      allow correction of measured Delta14C values for accurate and precise CSRA and
      are widely applicable to future archeological and biogeochemical studies.

PMID- 30220203
TI  - Error-Free Data Visualization and Processing through imzML and mzML Validation.
AB  - Open data formats are key to facilitating data processing, sharing, and
      integration. The imzML format ( http://imzml.org/ ) has drastically improved
      these aspects of mass spectrometry imaging data. Efficient processing of data
      depends on data sets which are consistent and adhere to the specifications;
      however, this is not always the case. Here we present a validation tool for data
      stored in both imzML and the HUPO-PSI mass spectrometery counterpart, mzML, to
      identify any deviations from the published (i)mzML standard which could cause
      issues for the user when visualizing or processing data. The tool is released in
      two forms, a graphical user interface (GUI) for ease of use, and a command line
      version to fit into existing workflows and pipelines. When certain known issues
      are encountered, such as the presence of negative values for the location of the
      binary data, the validator resolves the issue automatically upon saving. The GUI
      version of the validator also allows editing of the metadata included within the
      (i)mzML files in order to resolve inconsistencies. We also present a means of
      performing conditional validation on the metadata within (i)mzML files, where
      user-defined rules are validated against depending on whether specific metadata
      are present (or not). For example, if the MALDI term is present, then additional
      rules related to MALDI (such as the requirement of inclusion of laser parameters)
      can be validated against this. This enables a flexible and more thorough
      automated validation of (i)mzML data. Such a system is necessary for validating
      data against more comprehensive sets of metadata such as minimum reporting
      guidelines or metadata requirements prior to submission and acceptance of data to
      data repositories. We demonstrate how this tool can be used to validate against
      the proposed minimum reporting guidelines in MSI as well as institute specific
      metadata criteria. The validator tool is endorsed for validation of imzML (
      http://imzml.org/ ) and mzML ( http://www.psidev.info/mzml ) and is made
      available through the respective Web sites. The validator is also released as
      open source under Mozilla Public License 2.0 at
      https://gitlab.com/imzML/imzMLValidator .

PMID- 30220202
TI  - Non-Heme Diiron Model Complexes Can Mediate Direct NO Reduction: Mechanistic
      Insight into Flavodiiron NO Reductases.
AB  - Flavodiiron nitric oxide reductases (FNORs), a common enzyme family found in
      various types of pathogenic bacteria, are capable of reducing nitric oxide (NO)
      to nitrous oxide (N2O) as a protective detoxification mechanism. Utilization of
      FNORs in pathogenic bacteria helps them survive and proliferate in the human
      body, thus causing chronic infections. In this paper, we present a new diiron
      model complex, [Fe2((Py2PhO2)MP)(OPr)2](OTf), with bridging propionate ligands
      (OPr-) that is capable of directly reducing NO to N2O in quantitative yield
      without the need to (super)reduce the complex. We first prepared the diferric
      precursor and characterized it by UV-vis, IR, NMR and Mossbauer spectroscopies,
      cyclic voltammetry, and mass spectrometry. This complex can then conveniently be
      reduced to the diferrous complex using CoCp2. Even though this diferrous complex
      is highly reactive, we have successfully isolated and characterized this species
      using X-ray crystallography and various spectroscopic techniques. Most
      importantly, upon reacting this diferrous complex with NO gas, we observe
      quantitative formation of N2O via IR gas headspace analysis, the first
      demonstration of direct NO reduction by a non-heme diiron model complex. This
      finding directly supports recent mechanistic proposals for FNORs.

PMID- 30220204
TI  - Shotgun Proteomics Analysis of Saliva and Salivary Gland Tissue from the Common
      Octopus Octopus vulgaris.
AB  - The salivary apparatus of the common octopus ( Octopus vulgaris) has been the
      subject of biochemical study for over a century. A combination of bioassays,
      behavioral studies and molecular analysis on O. vulgaris and related species
      suggests that its proteome should contain a mixture of highly potent neurotoxins
      and degradative proteins. However, a lack of genomic and transcriptomic data has
      meant that the amino acid sequences of these proteins remain almost entirely
      unknown. To address this, we assembled the posterior salivary gland transcriptome
      of O. vulgaris and combined it with high resolution mass spectrometry data from
      the posterior and anterior salivary glands of two adults, the posterior salivary
      glands of six paralarvae and the saliva from a single adult. We identified a
      total of 2810 protein groups from across this range of salivary tissues and age
      classes, including 84 with homology to known venom protein families.
      Additionally, we found 21 short secreted cysteine rich protein groups of which 12
      were specific to cephalopods. By combining protein expression data with
      phylogenetic analysis we demonstrate that serine proteases expanded dramatically
      within the cephalopod lineage and that cephalopod specific proteins are strongly
      associated with the salivary apparatus.

PMID- 30220206
TI  - A Targeted Mass Spectrometry-Based Metabolomics Approach toward the Understanding
      of Host Responses to Huanglongbing Disease.
AB  - Candidatus Liberibacter asiaticus (CLas) is the major culprit of Huanglongbing
      (HLB), the most destructive citrus disease worldwide. The polymerase chain
      reaction (PCR) is the most common method for detecting the presence of CLas in
      the tree. However, due to the uneven distribution of bacteria and a minimum
      bacterial titer requirement, an infected tree may test false negative. Thus, our
      current study profiled primary and secondary metabolites of CLas-free leaves
      harvested from a citrus undercover protection system (CUPS) to prevent a
      misjudgment of CLas infection. Functional enrichment analysis revealed several
      metabolic pathways significantly affected by CLas infection, mainly biosynthesis
      of amino acids and secondary metabolites. Comparisons of CLas-infected metabolite
      alterations among oranges, mandarins, and grapefruits revealed that host
      responses to CLas were different. The metabolite signature highlighted in this
      study will provide a fuller understanding of how CLas bacteria affect the
      biosynthesis of primary and secondary metabolites in different hosts.

PMID- 30220207
TI  - Cyclic Hypervalent Iodine Reagents for Azidation: Safer Reagents and Photoredox
      Catalyzed Ring Expansion.
AB  - Azides are building blocks of increasing importance in synthetic chemistry,
      chemical biology, and materials science. Azidobenziodoxolone (ABX, Zhdankin
      reagent) is a valuable azide source, but its safety profile has not been
      thoroughly established. Herein, we report a safety study of ABX, which shows its
      hazardous nature. We introduce two derivatives, tBu-ABX and ABZ
      (azidobenziodazolone), with a better safety profile, and use them in established
      photoredox- and metal-mediated azidations, and in a new ring-expansion of
      silylated cyclobutanols to give azidated cyclopentanones.

PMID- 30220208
TI  - Tuning the pH Response of Weak Polyelectrolyte Brushes with Specific Anion
      Effects.
AB  - The positively charged poly( N, N'-dimethylaminoethyl methacrylate) (PDMAEMA)
      brushes have been employed as model weak polyelectrolyte brushes (WPBs) to
      demonstrate the tuning of the pH response of WPBs with specific anion effects.
      The charge density of PDMAEMA brushes can be modulated by specific ion-pairing
      interactions between counterions and the protonated dimethylamino group; as a
      result, the strength of the pH response of PDMAEMA brushes can be tuned by
      specific anion effects. A more chaotropic counterion can more strongly interact
      with the protonated dimethylamino group, thereby more effectively neutralizing
      the positively charged group associated with the grafted weak polyelectrolyte
      chains and more remarkably suppressing the pH response of PDMAEMA brushes.
      Although the pH response of PDMAEMA brushes is insensitive to the anion identity
      at a low salt concentration, it can be tuned by specific anion effects at
      relatively high salt concentrations. Our study demonstrates that the pH
      responsive properties of PDMAEMA brushes including hydration, conformation, oil
      wettability, and adhesion can be tuned by specific anion effects. The work
      presented here provides a method to tune the pH response of WPBs by the anion
      identity.

PMID- 30220205
TI  - Protocatechuic Acid Ameliorated Palmitic-Acid-Induced Oxidative Damage in
      Endothelial Cells through Activating Endogenous Antioxidant Enzymes via an
      Adenosine-Monophosphate-Activated-Protein-Kinase-Dependent Pathway.
AB  - Protocatechuic acid (PCA, 3,4-dihydroxybenzoic acid), the main metabolite of
      anthocyanins, is widely distributed in fruits and vegetables and has been
      reported to possess a strong antioxidant activity. Herein, we aimed to
      investigate the protective effect of PCA against high palmitic-acid (PA)-induced
      oxidative damage and the underling molecular mechanisms in human umbilical vein
      endothelial cells (HUVECs). PCA reduced the levels of intracellular reactive
      oxygen species and malondialdehyde and increased the activities of endogenous
      antioxidant enzymes, including superoxide dismutase, glutathione peroxidase 1,
      and heme oxygenase 1 (HO-1). Metabolomic analysis showed that PCA affected
      numerous metabolites, especially some of which were related with energy
      metabolism. PCA also upregulated the phosphorylation of adenosine-monophosphate
      activated protein kinase (AMPK) at Thr172 through activating liver kinase B1 and
      then promoted the expression of p-Nrf2 and HO-1. Moreover, PCA reversed the
      decreased expression of peroxisome proliferator-activated receptor gamma
      coactivator 1alpha and significantly increased the mitochondrial density.
      Collectively, these results demonstrated that PCA attenuated PA-induced oxidative
      damage in HUVECs via an AMPK-dependent pathway.

PMID- 30220209
TI  - Rotational Temperature Modeling of the Swan Deltanu = 0 Band Sequence in Comet
      122P/de Vico.
AB  - We modeled observations of the C2 d3Pig-a3Piu (Swan) Deltanu = 0 sequence
      observed in spectra of comet 122P/de Vico obtained with the 2.7 m Harlan J. Smith
      Telescope and Tull Coude spectrograph of McDonald observatory on 10/3/1995 and
      10/4/1995. The data used spanned 4986-5169 A at R = lambda/Deltalambda = 60 000.
      We used the PGOPHER molecular spectra model to generate and fit synthetic spectra
      with the d3Pig having one and two rotational temperatures. We found that the
      excited state had a two-component rotational temperature, similar to that found
      for comet Halley. The modeled spectrum was sufficiently high quality that local
      perturbations were important to include. The large perturbation, b3Sigmag-(nu =
      10), was added to our fits, and some new estimates of its molecular constants
      were found.

PMID- 30220210
TI  - Limits for Resolving Isobaric Tandem Mass Tag Reporter Ions Using Phase
      Constrained Spectrum Deconvolution.
AB  - A popular method for peptide quantification relies on isobaric labeling such as
      tandem mass tags (TMT), which enables multiplexed proteome analyses.
      Quantification is achieved by reporter ions generated by fragmentation in a
      tandem mass spectrometer. However, with higher degrees of multiplexing, the
      smaller mass differences between the reporter ions increase the mass resolving
      power requirements. This contrasts with faster peptide sequencing capabilities
      enabled by lowered mass resolution on Orbitrap instruments. It is therefore
      important to determine the mass resolution limits for highly multiplexed
      quantification when maximizing proteome depth. Here, we defined the lower
      boundaries for resolving TMT reporter ions with 0.0063 Da mass differences using
      an ultra-high-field Orbitrap mass spectrometer. We found the optimal method
      depends on the relative ratio between closely spaced reporter ions and that 64 ms
      transient acquisition time provided sufficient resolving power for separating TMT
      reporter ions with absolute ratio changes up to 16-fold. Furthermore, a 32 ms
      transient processed with phase-constrained spectrum deconvolution provides >50%
      more identifications with >99% quantified but with a slight loss in
      quantification precision and accuracy. These findings should guide decisions on
      what Orbitrap resolution settings to use in future proteomics experiments,
      relying on isobaric TMT reporter ion quantification.

PMID- 30220212
TI  - Perspectives on the Study of Fluorinated Alternatives.

PMID- 30220211
TI  - Unravelling the Self-Assembly of Diketopyrrolopyrrole-Based Photovoltaic
      Molecules.
AB  - The nanostructure of bulk heterojunction in an organic solar cell dominating the
      electron transport process plays an important role in improving the device
      efficiency. However, there is still a great need for further understanding the
      local nanostructures from the viewpoint of molecular design because of the
      complex alignment in the solid film. In this work, four kinds of photovoltaic
      materials containing a diketopyrrolopyrrole (DPP) unit combined with other
      different building blocks were selected and their self-assembled structures on a
      solid surface were studied by scanning tunneling microscopy technique in
      combination with theory calculations. The results reveal these DPP-based
      photovoltaic molecules self-assembled into different nanostructures, which
      strongly depend on the chemical structure, in particular the backbones and alkyl
      side chains. The planarities of backbones are affected both by molecule-substrate
      interaction and steric hindrance induced by the substituted thiophene or benzo[
      b]thiophene units on DPP and porphyrin building blocks. The substituted branched
      alkyl side chains are out of the plane, which are influenced by the alignments of
      molecular backbones. In addition, the solution concentration also shows a large
      effect on the self-assembled nanostructures. This systematic research on the self
      assembled structures of DPP-based semiconductors on a surface would provide
      guidance for designing materials and controlling the morphology of a
      donor/acceptor heterojunction system.

PMID- 30220213
TI  - The effect of perceived stress and specialization on the relationship between
      perfectionism and burnout in collegiate athletes.
AB  - BACKGROUND: Athletic burnout is common when demands of the sport exceed the
      rewards. Individuals with certain personality dispositions, such as
      perfectionism, are at increased risk of experiencing perceived stress and
      subsequent burnout (Fender, L. K. (1989). Athlete burnout: Potential for research
      and intervention strategies. The Sport Psychologist, 3, 63-71. doi:
      10.1123/tsp.3.1.63 ; Gould, D., Tuffey, S., Udry, E., & Loehr, J. (1996). Burnout
      in competitive junior tennis players: I. A quantitative psychological assessment.
      The Sport Psychologist, 10, 322-340. doi: 10.1123/tsp.10.4.322 ; Stoeber, J.
      (2011). The dual nature of perfectionism in sports: Relationships with emotion,
      motivation, and performance. International Review of Sport and Exercise
      Psychology, 4, 128-145. doi: 10.1080/1750984x.2011.604789 ). Perfectionism has
      both adaptive and maladaptive dimensions, with the more maladaptive qualities
      leading to greater perceived stress (Hamachek, D. E. (1978). Psychodynamics of
      normal and neurotic perfectionism. Psychology, 15, 27-33.; Rice, K. G., & Van
      Arsdale, A. C. (2010). Perfectionism, perceived stress, drinking to cope, and
      alcohol-related problems among college students. Journal of Counseling
      Psychology, 57, 439-450. doi: 10.1037/a0020221 ). OBJECTIVES: This study examined
      the influence of perfectionistic strivings and concerns on burnout, and perceived
      stress as a mediator of this relationship in Division II and III specialized and
      multiple-sport athletes (N = 351). DESIGN: Cross-Sectional. METHODS: Participants
      completed a demographic questionnaire and online measures of perfectionism,
      stress, and burnout during the latter part of the competitive season. RESULTS:
      Results showed a positive, direct effect of perfectionistic concerns on burnout.
      Stress partially mediated this relationship. Additionally, perfectionistic
      strivings had a negative direct effect on burnout for specialized athletes.
      CONCLUSION: The relationship between perfectionistic concerns and burnout is
      partially explained by stress. Multiple sport athletes showed lower levels of
      stress compared to specialized ones. Finally, perfectionistic strivings are
      associated with lower levels of burnout for specialized athletes.

PMID- 30220214
TI  - Serum microRNA as potential biomarker to detect breast atypical hyperplasia and
      early-stage breast cancer.
AB  - AIM: The present study aimed to identify microRNA (miRNA) that can be used for
      not only detecting early-stage breast cancer (BC) but also diagnosing atypical
      hyperplasia (AH). MATERIALS & METHODS: RT-qPCR detected the expression levels of
      miRNAs and receiver operating characteristic curves were constructed to evaluate
      sensitivity and specificity of the assay. RESULTS: miR-24 and miR-103a were
      expressed in an upward trend in serum of benign proliferative tumor subjects,
      while they were downregulated significantly in serum of AH (p < 0.005) and early
      stage BC subjects (p < 0.005) with high sensitivity and specificity as compared
      with controls. Bioinformatics analysis also revealed the potential molecular
      mechanism through which miR-24 and miR-103a regulate tumorigenesis in BC.
      CONCLUSION: miR-24 and miR-103a were valuable biomarkers for distinguishing AH
      and early-stage BC from healthy individuals/benign proliferative tumor patients.

PMID- 30220215
TI  - A combined compression molding, heating, and leaching process for fabrication of
      micro-porous poly(epsilon-caprolactone) scaffolds.
AB  - Biomaterial scaffolds have been increasingly used for tissue engineering
      applications as well as three dimensional (3D) cell culture models. Herein, we
      report a simple procedure combining compression molding, heating, and leaching
      methods for the fabrication of 3D micro-porous poly(epsilon-caprolactone) (PCL)
      biomaterial scaffolds. In this procedure, PCL micro particles are mixed with NaCl
      of defined sizes and compression molded, followed by heating and subsequent
      leaching of NaCl particles. This technique eliminates the gas foaming method,
      which is commonly used in the fabrication of PCL scaffolds. Process and scaffold
      parameters (i.e., heating time, NaCl concentration, and NaCl particle size) were
      varied and analyzed to determine their impact on the overall scaffold structural
      and mechanical properties. An increase in NaCl particle size led to an increase
      in pore area but did not significantly impact the mechanical properties of the
      scaffolds. Additionally, NaCl concentration did not show a significant effect on
      pore area, but considerably impacted the mechanical properties, water absorption
      capacity and porosity of the scaffolds. Variations in the heating time did not
      have an effect in the pore area, porosity, water absorption capacity or
      mechanical properties of the scaffolds. We also demonstrated the ability of these
      scaffolds to support the proliferation of breast cancer cells. Overall, these
      results elucidated structure-property relationships in the fabricated micro
      porous PCL scaffolds. Further, this procedure could be potentially scaled up for
      the fabrication of micro-porous PCL scaffolds.

PMID- 30220216
TI  - On the prediction of cytotoxicity of diverse chemicals for topminnow
      (Poeciliopsis lucida) hepatoma cell line, PLHC-1$.
AB  - Two data sets on the cytotoxicity of diverse chemicals to topminnow (Poeciliopsis
      lucida) hepatoma cell line (PLHC-1) were modelled with quantitative structure
      toxicity relationship (QSTR). The data sets are based on 3-amino-7-dimethylamino
      2-methylphenazine hydrochloride (NR) and 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) assays representing lysosomal damage and
      metabolic impairment, respectively. The descriptors were calculated with DRAGON 6
      and SPARTAN 10 software packages. Descriptor selection was made by 'all subset'
      and genetic algorithm-based features implemented in QSARINS software. The
      proposed QSTR models were validated both internally and externally. For both
      endpoints, statistically satisfactory QSTR models were generated with nTr = 39;
      r2Tr = 0.782; RMSETr = 0.466; nTest = 18; r2Test = 0.799; RMSETest = 0.360 for NR
      based model and nTr = 32; r2Tr = 0.775; RMSETr = 0.460; nTest = 10; r2Test =
      0.864; RMSETest = 0.290 for MTT-based model. Additionally, the QSTR models
      generated for NR and MTT endpoints were used to predict the cytotoxicity of an
      external set of 657 and 652 diverse chemicals with structural coverage of 98.6%
      and 98.3%, respectively. A moderate correlation was observed between the
      experimental in vivo and predicted in vitro values for external set chemicals.
      The QSTR models may provide an initial, rapid screening and prioritization of
      these diverse chemicals for the acute fish toxicity assessment and reduce the
      need for extensive in vivo toxicity testing.

PMID- 30220217
TI  - Classification models for identifying substances exhibiting acute contact
      toxicity in honeybees (Apis mellifera)$.
AB  - Nowadays, environmental and biological endpoints can be predicted with in silico
      approaches if sufficient experimental data of good quality are available. Since
      the experimental evaluation of acute contact toxicity towards honeybees (Apis
      mellifera) is a complex and expensive assay, the computational models that follow
      OECD principles for this endpoint prediction represent important alternatives for
      safety prioritisation of chemicals, especially pesticides. We developed and
      validated counter-propagation artificial neural network (CPANN) models for in
      silico evaluation of toxicity of pesticides towards honeybees by using new in
      house software. The data set included 254 pesticides with their toxicological
      experimental values (acute contact toxicity after 48 h of exposure - LD50
      [MUg/bee]). The 2D structures of compounds were mathematically represented with
      56 Dragon molecular descriptors (MDs). The two-category models were developed to
      separate compounds as toxic or non-toxic for two different thresholds: (i) toxic
      when LD50 < 1 MUg/bee and (ii) toxic when LD50 < 100 MUg/bee. The models give
      reliable predictions in an external validation set and cover a large structural
      space. They were applied to a structurally diverse data set of 395 experimentally
      untested pesticides; 19% of them were predicted as highly toxic towards bees.

PMID- 30220219
TI  - Improving Depression Outcome by Patient-Centered Medical Management.
AB  - Specific challenges that profoundly affect the outcome of treatment for
      depression include 1) patient engagement and retention in care and optimization
      of treatment adherence, 2) optimization of symptom and side effect control by
      medication adjustments using measurement-based care procedures, 3) restoration of
      daily functioning and quality of life, and 4) prevention or at least mitigation
      of symptomatic relapse or recurrence. According to data from the Sequenced
      Treatment Alternatives to Relieve Depression study, some 10%-15% of patients will
      not return for treatment after an initial thorough evaluation visit; an
      additional 20%-35% will not complete the first acute-phase treatment step, and
      another 20%-50% will not complete 6 months of continuation treatment. Among
      patients who stay in treatment, over 50% exhibit poor adherence. Thus, most
      patients do not overcome the first two challenges. There are no systematic,
      widely agreed-upon psychosocial approaches to any of these four major challenges.
      The authors propose "patient-centered medical management" to address each of the
      four challenges, using psychoeducational, behavioral, cognitive, interpersonal,
      and dynamic models and methods. A renewed emphasis on the development and testing
      of systematic approaches to overcoming these common clinical challenges could
      enhance the chances of patient recovery and care system cost efficiencies. [AJP
      AT 175: Remembering Our Past As We Envision Our Future July 1933:
      Psychotherapeutics at Stockbridge Horace K. Richardson: "Frequently, in the
      simpler situations, very few interviews are required in order that he [the
      patient] discover for himself what part of the adaptive machinery is at fault,
      and for him to develop a technique of handling the maladjustment on a more
      satisfactory level in the future."(Am J Psychiatry 1933; 90:45-56 )].

PMID- 30220218
TI  - 2D and 3D structure-activity modelling of mosquito repellents: a review $.
AB  - Repellents disrupt the behaviour of blood-seeking mosquitoes protecting humans
      against their bites which can transmit serious diseases. Since the mid-1950s, N,N
      diethyl-m-toluamide (DEET) is considered as the standard mosquito repellent
      worldwide. However, DEET presents numerous shortcomings. Faced with the
      heightening risk of mosquito expansion caused by global climate changes and
      increasing international exchanges, there is an urgent need for a better
      repellent than DEET and the very few other commercialised repelling molecules
      such as picaridin and IR3535. In silico approaches have been used to find new
      repellents and to provide better insights into their mechanism of action. In this
      context, the goal of our study was to retrieve from the literature all the papers
      dealing with qualitative and quantitative structure-activity relationships on
      mosquito repellents. A critical analysis of the SAR and QSAR models was made
      focusing on the quality of the biological data, the significance of the molecular
      descriptors and the validity of the statistical tools used for deriving the
      models. The predictive power and domain of application of these models were also
      discussed. The hypotheses to compute homology and pharmacophore models, their
      interest to find new repellents and to provide insights into the mechanisms of
      repellency in mosquitoes were analysed. The interest to consider the mosquito
      olfactory system as the target to compute new repellents was discussed. The
      potential environmental impact of these chemicals as well as new ways of research
      were addressed.

PMID- 30220220
TI  - Multimodal Structural Neuroimaging Markers of Brain Development and ADHD
      Symptoms.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a multifactorial
      disorder with diverse associated risk factors and comorbidities. In this study,
      the authors sought to understand ADHD from a dimensional perspective and to
      identify neuroanatomical correlates of traits and behaviors that span diagnostic
      criteria. METHODS: Multimodal neuroimaging data and multi-informant cognitive and
      clinical data were collected in a densely phenotyped pediatric cohort (N=160; 70
      with ADHD; age range, 9-12 years). Multivariate analysis identified associations
      between clinical and cognitive factors and multimodal neuroimaging markers
      (across tissue volume, cortical thickness, cortical area, and white matter
      microstructure). The resulting imaging markers were validated in an independent
      cohort (N=231; 132 with ADHD; age range, 7-18 years). RESULTS: Four novel
      patterns of neuroanatomical variation that related to phenotypic variation were
      identified. The first imaging pattern captured association of head size with sex,
      socioeconomic status, and mathematics and reading performance. The second pattern
      captured variation associated with development and showed that individuals with
      delayed development were more likely to be receiving ADHD medication. The third
      pattern was associated with hyperactivity, greater comorbidities, poorer
      cognition, lower parental education, and lower quality of life. The fourth
      pattern was associated with a particular profile of poorer cognition and
      irritability independent of ADHD. The authors further demonstrated that these
      imaging patterns could predict variation in age and ADHD symptoms in an
      independent cohort. CONCLUSIONS: The findings suggest that ADHD presentation may
      arise from a summation of several clinical, developmental, or cognitive factors,
      each with a distinct neuroanatomical foundation. This informs the neurobiological
      foundations of ADHD and highlights the value of detailed phenotypic data in
      understanding the neurobiology underlying neurodevelopmental disorders.

PMID- 30220221
TI  - Maternal Immune Activation and Neuropsychiatric Illness: A Translational Research
      Perspective.
AB  - Epidemiologic studies, including prospective birth cohort investigations, have
      implicated maternal immune activation in the etiology of neuropsychiatric
      disorders. Maternal infectious pathogens and inflammation are plausible risk
      factors for these outcomes and have been associated with schizophrenia, autism
      spectrum disorder, and bipolar disorder. Concurrent with epidemiologic research
      are animal models of prenatal immune activation, which have documented
      behavioral, neurochemical, neuroanatomic, and neurophysiologic disruptions that
      mirror phenotypes observed in these neuropsychiatric disorders. Epidemiologic
      studies of maternal immune activation offer the advantage of directly evaluating
      human populations but are limited in their ability to uncover pathogenic
      mechanisms. Animal models, on the other hand, are limited in their
      generalizability to psychiatric disorders but have made significant strides
      toward discovering causal relationships and biological pathways between maternal
      immune activation and neuropsychiatric phenotypes. Incorporating these risk
      factors in reverse translational animal models of maternal immune activation has
      yielded a wealth of data supporting the predictive potential of epidemiologic
      studies. To further enhance the translatability between epidemiology and basic
      science, the authors propose a complementary approach that includes
      deconstructing neuropsychiatric outcomes of maternal immune activation into key
      pathophysiologically defined phenotypes that are identifiable in humans and
      animals and that evaluate the interspecies concordance regarding interactions
      between maternal immune activation and genetic and epigenetic factors, including
      processes involving intergenerational disease transmission. [AJP AT 175:
      Remembering Our Past As We Envision Our Future October 1857: The Pathology of
      Insanity J.C. Bucknill: "In the brain the state of inflammation itself either
      very quickly ceases or very soon causes death; but when it does cease it leaves
      behind it consequences which are frequently the causes of insanity, and the
      conditions of cerebral atrophy."(Am J Psychiatry 1857; 14:172-193 )].

PMID- 30220222
TI  - An alternative stereoselective total synthesis of (-)-pyrenophorol.
AB  - The total synthesis of 16-membered C2-Symmetric dilactone (-)-Pyrenophorol was
      accomplished starting from commercially available (S)-epoxide prepared by
      hydrolytic kinetic resolution of (+/-) - epoxide with key steps of Grignard
      reaction, Swern oxidation, Wittig reaction and cyclization was achieved by
      intermolecular Mitsunobu cyclization. The synthesis of (-)-Pyrenophorol
      accomplished from cheaply available starting material, easily work-up procedures
      and reduction of cost in industrial process were major advantages of this route.

PMID- 30220223
TI  - Prediction of chlortetracycline adsorption on the Fe3O4 nanoparticle using
      molecular dynamics simulation.
AB  - Molecular dynamics (MD) simulation was applied to investigate the adsorption
      mechanism of chlortetracycline (CTC) antibiotic molecule as the aqueous pollutant
      on the Fe3O4 nanoparticle (NP). Two different NP sizes with a diameter of about
      1.4nm and 3.5nm were selected. Initially, the stability of both nanoparticles in
      water was investigated by calculating radial distribution function curves of NP
      atoms. Simulation results confirmed the stable crystallographic structures of
      both NPs. However, small NP induce greater structural stabilization. Then, CTC
      molecules were adsorbed on NPs surface in various pollutant concentrations.
      Electrostatic and hydrogen bond were the major types of interactions between CTC
      molecules and the adsorbent surface. CTC molecules formed a complex with NP
      surface from their amine side chains; while they were parallel to each other in
      their aromatic rings and pi-pi bond between two CTC molecules was formed.
      Diffusion rate of CTC molecules could predict the adsorption mechanism. At lower
      concentration of CTC, CTC molecules tend to adsorb on the NP surface. At these
      concentrations, the diffusion rate of CTC was high. By increasing the CTC
      concentration, the pollutant agglomeration was enhanced which decreased the
      diffusion rate. At this time, the surface of NP was saturated. In addition, the
      results of isotherm curves showed that CTC adsorption on small nanoparticles
      could be defined with both Langmuir and Freundlich isotherm models, while
      Freundlich isotherm model was more appropriate for larger NPs. In conclusion,
      observations confirmed that MD simulation could successfully predict the behavior
      of CTC adsorption on the Fe3O4 NP surface.

PMID- 30220224
TI  - Preserving quality of life as a key treatment goal in advanced soft tissue
      sarcomas.
AB  - INTRODUCTION: Health-related quality of life (HRQoL) is a patient-reported
      outcome that addresses patients' perceptions of symptoms across physical,
      emotional, cognitive and social domains. As HRQoL is currently rarely measured
      outside clinical trials in oncology, it must be inferred from patients' everyday
      performance during treatment. To gain insight into the HRQoL of advanced STS
      patients receiving palliative treatment in clinical practice, three case studies
      of patients treated with trabectedin are examined. Areas covered: The patient in
      Case 1 has maintained complete remission for more than 8 years after receiving
      nine cycles of second-line trabectedin followed by secondary surgery for
      recurrent myxoid liposarcoma, and was able to resume normal activities during
      trabectedin treatment. Case 2 describes 10 years' follow-up of a patient with
      myxoid liposarcoma who remains well after many lines of chemotherapy including
      extended use of trabectedin in the second line. The third case illustrates the
      feasibility of extending survival time in an elderly patient with metastatic
      leiomyosarcoma who was able to maintain a busy and active lifestyle while
      receiving second-line trabectedin. Expert commentary: Owing to its relatively
      benign safety profile, trabectedin frequently permits prolonged therapy and is
      generally well tolerated, often allowing patients to carry on with normal daily
      activities.

PMID- 30220225
TI  - Chronic orofacial pain animal models - progress and challenges.
AB  - INTRODUCTION: Chronic orofacial pain is one of the most common pain conditions
      experienced by adults. Animal models are often selected as the most useful
      scientific methodology to explore the pathophysiology of the disorders that cause
      this disabling pain to facilitate the development of new treatments. The creation
      of new models or the improvement of existing ones is essential for finding new
      ways to approach the complex neurobiology of this type of pain. Areas covered:
      The authors describe and discuss a variety of animal models used in chronic
      orofacial pain (COFP). Furthermore, they examine in detail the mechanisms of
      action involved in orofacial neuropathic pain and orofacial inflammatory pain.
      Expert opinion: The use of animal models has several advantages in chronic
      orofacial pain drug discovery. Choosing an animal model that most closely
      represents the human disease helps to increase the chances of finding effective
      new therapies and is key to the successful translation of preclinical research to
      clinical practice. Models using genetically modified animals seem promising but
      have not yet been fully developed for use in chronic orofacial pain research.
      Although animal models have provided significant advances in the pharmacological
      treatment of orofacial pain, several barriers still need to be overcome for
      better treatment options.

PMID- 30220226
TI  - Platelet-rich plasma is a useful therapeutic option in melasma.
AB  - BACKGROUND: Melasma is a cosmetically disfiguring disorder of facial
      pigmentation. OBJECTIVES: We evaluated the value of platelet-rich plasma (PRP) in
      the treatment of melasma using two different delivery techniques: microneedling
      using dermapen versus microinjections using mesoneedles. PATIENTS AND METHODS:
      Twenty-three adult Egyptian melasma patients were enrolled. Wood's light was used
      to determine the histological type of melasma. Autologous PRP was delivered into
      the lesional melasma skins through microneedling with dermapen on the right side
      of the face and intradermal microinjections using mesoneedles on the left side of
      the face (for each patient). The treatment was done regularly (three sessions,
      each month). The response to PRP therapy was measured using melasma area and
      severity index (MASI) and modified melasma area and severity index (mMASI) that
      were calculated before and after three treatment sessions. Hemi-MASI was used to
      compare the effectiveness of the two delivery techniques. RESULTS: Following PRP
      treatment, MASI and mMASI scores decreased significantly from 11.86 +/- 5.25 to
      6.96 +/- 4.82, and from 5.71 +/- 2.56 to 2.90 +/- 2.05, respectively (p < .000,).
      A statistically significant decrease was noted in the hemi-MASI score on each
      side of the face following PRP treatment (p < .000), but there was no significant
      difference in comparing both sides. CONCLUSIONS: Our study provides the first
      indication about the value of PRP as a useful and new therapeutic option in
      melasma. Moreover, our study was the first to compare PRP delivery through
      microneedling versus microinjections.

PMID- 30220227
TI  - Going gluten free in non-celiac autoimmune diseases: the missing ingredient.

PMID- 30220228
TI  - Nonbiological therapeutic management of ulcerative colitis.
AB  - INTRODUCTION: Treatment of ulcerative colitis (UC) is constantly evolving. In the
      last two decades, new therapeutic strategies have been implemented by addressing
      specific disease mechanisms: biological agents against tumor necrosis factor
      alpha and integrins are now widely used, and more agents targeting different
      pathological pathways are being marketed. Despite these novel therapies,
      nonbiological drugs are still the mainstay of treatment, especially in mild-to
      moderate disease, since a proven safety and tolerability profile is observed.
      Excellent efficacy both in induction and maintenance of remission is obtained,
      with a lower cost compared to biological agents. Areas covered: The purpose of
      this review is to summarize the current knowledge and the latest clinical
      evidence regarding nonbiological therapies for UC. Expert opinion: Concomitant
      administration of oral and rectal 5-aminosalicylates acid is more effective in
      the treatment of UC in remission. Corticosteroids are the treatment of choice in
      patients with moderately severe or severe UC. The association of azathioprine
      with biological treatments is more effective than monotherapy. Cyclosporine is an
      effective drug in severe UC, but its poor management must be considered.
      Probiotics are very popular; however, evidence on their actual role in UC still
      must be demonstrated; cytapheresis plays only a niche role at this time.

PMID- 30220230
TI  - Clinical review of Clostridium difficile infection: an update on treatment and
      prevention.
AB  - INTRODUCTION: Clostridium difficile infection (CDI) has become a significant
      healthcare-associated infection and is strongly associated with antibiotic use.
      Practice guidelines have recently been revised incorporating updated
      recommendations for diagnosis, treatment, and prevention. Areas covered: This
      review discusses updated aspects of CDI management. New and emerging
      pharmacologic options for treatment and prevention are reviewed. Expert opinion:
      Metronidazole is associated with lower rates of treatment success compared to
      vancomycin and should no longer be used as primary therapy for the first episode
      of CDI or recurrent disease. Vancomycin or fidaxomicin are now recommended for
      first-line therapy for most cases of CDI. Fecal microbiota transplant is
      effective and safe for the treatment of recurrent CDI. Evidence supports the use
      of fidaxomicin and bezlotoxumab for prevention of recurrent CDI; however, the
      costs associated with these therapies may limit their use. Validated risk
      prediction tools are needed to identify patients most likely to benefit from
      these treatments. Future advancements in microbiota targeting treatments will
      emerge as promising alternatives to standard CDI treatments. Antibiotic
      stewardship and infection control measures will remain essential components for
      CDI management.

PMID- 30220231
TI  - Plasminogen activator inhibitor-1 is involved in interleukin-1beta-induced matrix
      metalloproteinase expression in murine chondrocytes.
AB  - OBJECTIVES: Interleukin (IL)-1beta and matrix metalloproteinases (MMPs) play
      important roles in the pathogenesis of osteoarthritis. On the other hand,
      plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, exerts
      functions in the pathogenesis of various diseases. However, the functional roles
      of PAI-1 in the chondrocytes have been still remained unknown. METHODS: In the
      present study, we investigated the roles of PAI-1 in the effects of IL-1beta on
      the chondrocytes using wild-type and PAI-1-deficient mice. RESULTS: IL-1beta
      significantly elevated PAI-1 mRNA levels in the chondrocytes from wild-type mice.
      PAI-1 deficiency significantly blunted the mRNA levels of TGF-beta and IL-6
      enhanced by IL-1beta in murine chondrocytes. Moreover, PAI-1 deficiency
      significantly decreased the mRNA levels of MMP-13, -3 and -9 as well as MMP-13
      activity enhanced by IL-1beta in the chondrocytes. In addition, PAI-1 deficiency
      significantly reversed type II collagen mRNA levels suppressed by IL-1beta in the
      chondrocytes. On the other hand, active PAI-1 treatment significantly enhanced
      the mRNA levels of MMP-13, -3 and -9 as well as decreased type II collagen mRNA
      levels in the chondrocytes from wild-type mice. CONCLUSION: We first demonstrated
      that PAI-1 is involved in MMP expression enhanced by IL-1beta in murine
      chondrocytes. PAI-1 might be crucial for the cartilage matrix degradation and the
      impaired chondrogenesis by IL-1beta in mice.

PMID- 30220232
TI  - Drug discovery strategies and the preclinical development of D-amino-acid oxidase
      inhibitors as antipsychotic therapies.
AB  - INTRODUCTION: D-amino-acid oxidase (DAAO) degrades D-serine, a co-agonist of the
      NMDA receptor whose dysfunction is involved in the positive, negative, and
      cognitive symptoms of schizophrenia. The inhibition of DAAO appears to be a
      viable strategy to increase D-serine level and to have therapeutic potential in
      schizophrenia. Areas covered: This review describes the efforts to develop DAAO
      inhibitors and to optimize their in vitro and in vivo effects in preclinical
      settings. The structural evolution of DAAO inhibitors is presented from simple
      carboxylic acid derivatives via small, planar compounds with carboxylic acid
      mimetics to extended compounds whose binding is possible owing to DAAO
      flexibility. Inhibitory potency and pharmacokinetic properties are discussed in
      the context of compounds' ability to increase D-serine level and to show efficacy
      in animal models of schizophrenia. Expert opinion: The accumulated knowledge on
      the structural requirements of DAAO inhibitors and on their in vitro and in vivo
      effects provides appropriate basis to develop inhibitors with optimized potency,
      selectivity and pharmacokinetic profile including blood-brain penetration. In
      addition, the validation of DAAO inhibition therapy in alleviating the symptoms
      of schizophrenia requires further studies on the efficacy of DAAO inhibitors in
      behavioral assays of animals and on the species differences in D-serine
      metabolism.

PMID- 30220233
TI  - Can pharmacotherapy help persistent genital arousal disorder?
AB  - INTRODUCTION: Persistent genital arousal disorder (PGAD) is a presumably rare,
      although debilitating condition, which was first defined only at the beginning of
      this century and has not yet found consideration by any of the international
      classification systems of diseases. As affected patients can suffer tremendously,
      this report aims at providing an overview and an expert opinion on the few
      existing studies and case reports, guiding clinicians in the treatment and
      pharmacotherapy of PGAD. Areas covered: In this article case reports, case series
      and surveys on drugs that may both alleviate or worsen/induce PGAD are reported.
      Expert opinion: Data on pharmacological treatment options in PGAD are sparse and
      mainly rely on case reports making conclusions difficult. Most importantly, some
      drugs such as serotonin reuptake inhibitors (SSRIs) may even induce or worsen
      PGAD during treatment or withdrawal. We now need an initial spark in order to
      promote basic research on the etiology of PGAD as well as clinical trials on
      possible treatment options. In the meanwhile, clinicians should provide careful
      diagnostics and counseling for affected patients. In case pharmacotherapy is
      desired, drugs that are able to inhibit sexual excitation and/or modulate sensory
      perception such as pregabalin or duloxetin might be worth a trial.

PMID- 30220229
TI  - Target-based drug discovery through inversion of quantitative structure-drug
      property relationships and molecular simulation: CA IX-sulphonamide complexes.
AB  - In this work, a target-based drug screening method is proposed exploiting the
      synergy effect of ligand-based and structure-based computer-assisted drug design.
      The new method provides great flexibility in drug design and drug candidates with
      considerably lower risk in an efficient manner. As a model system, 45
      sulphonamides (33 training, 12 testing ligands) in complex with carbonic
      anhydrase IX were used for development of quantitative structure-activity
      lipophilicity (property)-relationships (QSPRs). For each ligand, nearly 5,000
      molecular descriptors were calculated, while lipophilicity (logkw) and inhibitory
      activity (logKi) were used as drug properties. Genetic algorithm-partial least
      squares (GA-PLS) provided a QSPR model with high prediction capability employing
      only seven molecular descriptors. As a proof-of-concept, optimal drug structure
      was obtained by inverting the model with respect to reference drug properties.
      3509 ligands were ranked accordingly. Top 10 ligands were further validated
      through molecular docking. Large-scale MD simulations were performed to test the
      stability of structures of selected ligands obtained through docking complemented
      with biophysical experiments.

PMID- 30220234
TI  - Lenvatinib as a therapy for unresectable hepatocellular carcinoma.
AB  - INTRODUCTION: Since 2007 Sorafenib has represented the only approved drug for
      first-line treatment of advanced hepatocellular carcinoma (HCC). Lenvatinib, an
      orally active inhibitor of multiple receptor tyrosine kinases (VEGFR 1-3, FGFR 1
      4, PDGFRa, RET and KIT), showed preclinical and clinical activity in the
      treatment of solid tumors, including HCC. Areas covered: In this review, we
      summarize the current therapeutic paradigm for the systemic treatment of advanced
      HCC, focusing on Lenvatinib pre-clinical and clinical development. Keywords
      'Lenvatinib', ' Target therapy', 'REFLECT trial', 'Hepatocellular carcinoma',
      'HCC', 'Sorafenib' were used for literature search on PubMed. Expert commentary:
      In Phase-III multicentric REFLECT trial Lenvatinib demonstrated a non-inferior
      overall survival (OS) compared to Sorafenib in the first-line treatment of
      advanced HCC, with a manageable toxicity profile, becoming a valid alternative
      option in the therapeutic repertoire of this disease. Nevertheless, the potential
      role of Lenvatinib in real-life clinical practice has still to be defined,
      especially in the light of the positive results that have been achieved with
      other new therapeutic agents (e.g. immunotherapy).

PMID- 30220236
TI  - A standard model of Alzheimer's disease?
AB  - The recent Research Framework proposed by the US National Institute on Aging and
      the Alzheimer's Association (NIA-AA) recommends that Alzheimer's disease be
      defined by its specific biology rather than by non-specific neurodegenerative and
      syndromal features. By affirming markers of abnormal Abeta and tau proteins as
      the essential pathobiological signature of Alzheimer's disease, the Framework
      tacitly reinforces the amyloid (Abeta) cascade as the leading theory of Alzheimer
      pathogenesis. In light of recent evidence that the cascade is driven by the
      misfolding and templated aggregation of Abeta and tau, we believe that an
      empirically grounded Standard Model of Alzheimer's pathogenesis is within reach.
      A Standard Model can clarify and consolidate existing information, contextualize
      risk factors and the complex disease phenotype, identify testable hypotheses for
      future research, and pave the most direct path to effective prevention and
      treatment.

PMID- 30220237
TI  - Clinical effectiveness and long-term retention of abatacept in elderly rheumatoid
      arthritis patients: Results from a multicenter registry system.
AB  - OBJECTIVE: To study the clinical effectiveness and long-term retention rate of
      abatacept (ABA) in elderly rheumatoid arthritis (RA) patients in daily clinical
      practice. METHODS: A retrospective cohort study was performed using data from a
      multicenter registry. Our study population comprised 500 consecutive RA patients
      treated with ABA. We compared clinical effectiveness and ABA retention rates
      between the Young (<= 62 years), Middle (62 to 72 years), and Elderly (>= 72
      years) groups. We also performed separate examinations to identify predictive
      factors for ABA discontinuation in those with versus those without concomitant
      methotrexate (MTX) treatment. RESULTS: Mean age was 52.7 years in the Young
      group, 67.7 years in the Middle group, and 78.1 years in the Elderly group. No
      significant group-dependent differences were found in mean DAS28 score,
      categorical distribution of DAS28, and EULAR response rate across the 52 weeks.
      The ABA retention rates at 3 years as determined by the Kaplan-Meier method were
      similar in all three groups. Patient age was not a significant predictor of ABA
      discontinuation due to adverse events in patients with concomitant MTX; however,
      it was found to be a significant predictor for those who did not use MTX (Cox
      hazard model). CONCLUSIONS: ABA would be a reasonable treatment option for
      elderly RA patients from the viewpoints of both clinical effectiveness and long
      term retention. However, physicians should watch carefully for any serious
      adverse reactions in elderly RA patients with intolerance to MTX.

PMID- 30220238
TI  - Role of omega-3 polyunsaturated fatty acids in preventing gastrointestinal
      cancers: current status and future perspectives.
AB  - INTRODUCTION: Although inflammation is defensive and healing process that
      maintains organ homeostasis, unresolved inflammation can lead to diseases.
      Polyunsaturated fatty acids (PUFAs), especially n-6 PUFAs abundant in Western
      diet, are precursors of pro-inflammatory mediators, whereas n-3 PUFAs possess
      anti-inflammatory properties. Therefore, interest in the cancer-preventive effect
      of n-3 PUFAs is increasing. Areas covered: We have observed significant
      reductions of gastrointestinal tumorigenesis in the Fat-1 transgenic mouse as
      evidenced that the decrease in Helicobacter pylori-infected gastric
      tumorigenesis, colon, biliary, and pancreatic cancer was seen in Fat-1 mice
      producing n-3 PUFAs. However, despite many studies showing benefits, evidence
      based medicine regarding molecular pathology, epidemiology, and clinical
      achievement of cancer prevention of n-3 PUFAs are still limited. Expert
      commentary: Primary deficiency of eicosapentaenoic acids and docosahexaenoic
      acids in Western diets can explain the risk of cancer development and the
      importance of n-3/n-6 PUFA ratio in reducing cancer risk. Alteration of cell
      membrane composition during carcinogenesis is particularly important, due to
      increased rate of lipid/cholesterol synthesis in cancerous tissues. Here, we
      discuss that direct incorporation of n-3 PUFAs in the cell membrane corrects
      abnormal cellular proliferation and decreases inflammation-associated
      carcinogenesis. This is exemplified by cancer-preventive effects of n-3 PUFAs as
      fat sources for gastrointestinal cancers.

PMID- 30220235
TI  - Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis.
AB  - BACKGROUND: Nintedanib is an approved treatment for idiopathic pulmonary fibrosis
      (IPF). A subgroup analysis of a previously published trial suggested that
      sildenafil may provide benefits regarding oxygenation, gas exchange as measured
      by the diffusion capacity of the lungs for carbon monoxide (DlCO), symptoms, and
      quality of life in patients with IPF and severely decreased DlCO. That idea was
      tested in this trial. METHODS: We randomly assigned, in a 1:1 ratio, patients
      with IPF and a DlCO of 35% or less of the predicted value to receive nintedanib
      at a dose of 150 mg twice daily plus sildenafil at a dose of 20 mg three times
      daily (nintedanib-plus-sildenafil group) or nintedanib at a dose of 150 mg twice
      daily plus placebo three times daily (nintedanib group) for 24 weeks. The primary
      end point was the change from baseline in the total score on the St. George's
      Respiratory Questionnaire (SGRQ) at week 12 (the total score ranges from 0 to
      100, with higher scores indicating worse health-related quality of life).
      Secondary end points included measures of dyspnea and safety. RESULTS: A total of
      274 patients underwent randomization. There was no significant difference in the
      adjusted mean change from baseline in the SGRQ total score at week 12 between the
      nintedanib-plus-sildenafil group and the nintedanib group (-1.28 points and -0.77
      points, respectively; P=0.72). A benefit from sildenafil treatment was not
      observed with regard to dyspnea as measured with the use of the University of
      California, San Diego, Shortness of Breath Questionnaire. No new safety signals
      were observed, as compared with previous trials. CONCLUSIONS: In patients with
      IPF and a DlCO of 35% or less of the predicted value, nintedanib plus sildenafil
      did not provide a significant benefit as compared with nintedanib alone. No new
      safety signals were identified with either treatment regimen in this population
      of patients. (Funded by Boehringer Ingelheim; INSTAGE ClinicalTrials.gov number,
      NCT02802345 .).

PMID- 30220239
TI  - The uncertainties of the diagnosis and treatment of a suspected urinary tract
      infection in elderly hospitalized patients.
AB  - INTRODUCTION: The diagnostic criteria for a urinary tract infection (UTI) and
      proper treatment of elderly patients hospitalized with nonspecific symptoms is
      uncertain. Areas covered: A nonsystematic literature review of the variable
      approaches in diagnosing and treating hospitalized elderly patients with a
      suspected UTI. Expert commentary: Bacteriuria and/or pyuria cannot confirm the
      diagnosis of a UTI because of the high prevalence in the elderly regardless of
      presentation so urine cultures are not indicated in those hospitalized for
      diseases outside the urinary tract. The microscopic urinalysis is imprecise and
      inaccurate, and lowers the sensitivity in detecting a bacteremic UTI if used to
      confirm a positive dipstick test result. There is some evidence that cancelling
      urine cultures in the absence of a positive dipstick (negative leukocyte esterase
      and nitrite) is safe and prevents unnecessary antibiotic therapy. Urinary
      catheterization to obtain a urine sample is common in the elderly and it is
      unclear if changes in antibiotic therapy based on culture results outweighs the
      risks of the procedure. In hospitalized elderly patients without septic shock, it
      is unclear when it is safe to withhold antibiotic therapy, and when patients with
      criteria used to define severe sepsis need immediate treatment with broad
      spectrum antibiotics.

PMID- 30220240
TI  - Effect of Anti-tumor necrosis factor alpha treatment on radiographic progression
      in patient with ankylosing spondylitis: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Efficacy of anti-tumor necrosis factor (anti-TNF)alpha treatment in
      patient with active ankylosing spondylitis (AS) had been proved by many clinical
      studies. Inflammation and new bone formation in spine were two pivotal aspects in
      AS. TNF alpha inhibitor could eliminate inflammation including clinical and
      laboratory inflammatory manifestation. Paradoxical results whether TNF alpha
      antagonist could delay radiographic progression in AS were often been reported
      simultaneously. OBJECTIVES: To review literature about effect of TNF alpha
      inhibitor on radiographic progression and disease activity in patient with AS.
      METHODS: We conducted comprehensive search including Medline, EMBASE and the
      Cochrane Library from Jan. 1, 2000 to Aug. 15, 2017. Two reviewers independently
      supplemented with hand searching for the reference lists of inclusion. All trials
      focusing on radiographic progression or disease activity in patients with AS
      treated with anti-TNF alpha agents. Primary outcomes were modified Stokes AS
      Spinal Score (mSASSS), as well as Bath AS disease activity index (BASDAI) and
      Bath AS functional index (BASFI). Two reviewers independently selected studies
      and analyzed data. Methodological quality was assessed using the Newcastle-Ottawa
      scale (NOS).We pooled effects recorded on different scales as Standardized mean
      differences (SMDs) with 95% confidence intervals (CIs) using random-effects
      models. RESULTS: We included 14 studies of low to moderate risk of bias with
      3,186 patients, compared with control group, there was no effect of mSASSS
      changes (SMD=-0.12, 95%CI -1.17 to 0.93, P value = 0.82, I2=95%) and follow-up
      (SMD = 0.03, 95%CI 0.21 to 0.26, P value = 0.82, I2=36%) estimation in anti-TNF
      alpha group. However anti-TNF alpha agent treatment led to remarkable
      improvements on both Bath AS disease activity index (BASDAI) (SMD = 1.06, 95%CI
      0.22 to 1.89, P value = 0.01, I2=96%) and Bath AS functional index (BASFI) (SMD =
      0.93, 95%CI 0.24 to 1.92, P value = 0.01, I2=97%) scores at 12weeks. CONCLUSIONS:
      Our meta-analysis found no significant effect on delaying radiographic
      progression in AS treated with TNF alpha inhibitor, although TNF alpha inhibitor
      could do improve significantly disease activity and physical function in AS.

PMID- 30220241
TI  - Delivering Collaborative Care in Rural Settings: Integrating Remote
      Teleconsultation and Local Supervision in Rural Nepal.
AB  - The collaborative care model can deliver high-quality mental health care. In
      rural regions, clinical supervision is conducted remotely rather than in person.
      The authors implemented a remote teleconsultation model in rural Nepal, where the
      consulting psychiatrist is over 30 hours away. This column describes strategies
      for several challenges: poor mental health competencies and high turnover among
      primary care providers; need for urgent consultations; psychiatrist discomfort
      with lack of direct patient contact; unreliable electricity, technological tools,
      documentation, and delivery of treatment recommendations; on-site clinicians' low
      motivation to accept psychiatrist recommendations; and mismatch between the
      psychiatrist's recommendations and the site's capacity to implement them.

PMID- 30220243
TI  - "Why Me?" Understanding the HCV Care Continuum Among People With Serious Mental
      Illness.
AB  - OBJECTIVE: Despite possible cure rates of >90% with new treatment, people with
      serious mental illness are rarely screened for hepatitis C virus (HCV). A
      colocated approach may help patients navigate the care continuum. METHODS: This
      study used a mixed-methods approach to increase understanding of the HCV care
      continuum for people with mental illness (N=170). Quantitative data included
      laboratory testing, risk assessments, and chart reviews. Qualitative interviews
      (N=9) were conducted to gain a broader understanding. RESULTS: Thirty-one (18%)
      patients tested positive for HCV; 13 were cured of HCV, and 10 are still
      receiving treatment. Qualitative interviews revealed that fear of the diagnosis
      may be an important treatment barrier. CONCLUSIONS: Those with serious mental
      illness who were diagnosed as having HCV and received the colocated prevention
      and treatment program were able to navigate the continuum of care for HCV
      treatment. Fear of diagnosis may be an important consideration for future
      efforts.

PMID- 30220242
TI  - Mechanisms of Action and Outcomes for Students in Recovery Colleges.
AB  - OBJECTIVE: Recovery colleges are widespread, with little empirical research on
      how they work and the outcomes they produce. This study aimed to coproduce a
      change model characterizing mechanisms of action (how they work) and outcomes
      (their impact) for mental health service users who attend recovery colleges.
      METHODS: A systematized review identified all publications about recovery
      colleges. Inductive collaborative data analysis of 10 key publications by
      academic researchers and coresearchers with lived experience informed a
      theoretical framework for mechanisms of action and student outcomes, which was
      refined through deductive analysis of 34 further publications. A change model was
      coproduced and refined through stakeholder interviews (N=33). RESULTS: Four
      mechanisms of action for recovery colleges were identified: empowering
      environment (safety, respect, and supporting choices), enabling different
      relationships (power, peers, and working together), facilitating personal growth
      (for example, coproduced learning, strengths, and celebrating success), and
      shifting the balance of power through coproduction and reducing power
      differentials. Outcomes were change in the student (for example, self
      understanding and self-confidence) and changes in the student's life (for
      example, occupational, social, and service use). A coproduced change model
      mapping mechanisms of action to outcomes was created. CONCLUSIONS: Key features
      differentiate recovery colleges from traditional services, including an
      empowering environment, enabling relationships, and growth orientation. Service
      users who lack confidence, those with whom services struggle to engage, those who
      will benefit from exposure to peer role models, and those lacking social capital
      may benefit most. As the first testable characterization of mechanisms and
      outcomes, the change model allows formal evaluation of recovery colleges.

PMID- 30220244
TI  - Impact of a Care Management Entity on Use of Psychiatric Services Among Youths
      With Severe Mental or Behavioral Disorders.
AB  - OBJECTIVE: Care management entity models have a positive impact on functioning
      and symptom control among youths with serious emotional and behavioral disorders.
      However, little is known about whether treatment benefits are sustained after
      discharge. The study objective was to examine the association between enrollment
      in a care management entity and mental health outcomes during the year after
      discharge. METHODS: Data from care management entity administrative claims were
      linked with Medicaid claims for youths enrolled in a care management entity
      anytime from December 2009 through December 2013. Inverse probability treatment
      weighting was used to balance baseline characteristics between the youths
      enrolled in the care management entity and a comparison group. Study outcomes
      were psychiatry-related hospitalizations and emergency department (ED) visits
      during the year after discharge. Two models were used to compare the two groups,
      one modeling the probability of using any psychiatric service and one modeling
      the number of visits for each outcome among users of either service. RESULTS:
      After adjustment with inverse probability treatment weighting, 2,381 youths (care
      management, N=488; comparison, N=1,893) were identified. Care management was
      associated with a significantly lower likelihood of any psychiatry-related ED
      visit (odds ratio [OR]=.65, p=.017) and any psychiatric hospitalization (OR=.60,
      p=.011). No significant differences in outcomes were observed when the comparison
      was limited to users of services. CONCLUSIONS: Reduced use of psychiatric
      inpatient and ED services among youths enrolled in a care management entity was
      sustainable after discharge. Multiagency collaboration is needed to enrich the
      ability to assess outcomes across broader domains.

PMID- 30220245
TI  - Psychosis Literacy Among Latinos With First-Episode Psychosis and Their
      Caregivers.
AB  - OBJECTIVE: The study examined psychosis literacy among Latinos with first-episode
      psychosis (FEP) and their caregivers. The authors tested a model that knowledge
      of psychosis and attribution of illness to psychosis predicted professional help
      seeking in a cross-sectional design. METHODS: The sample (N=148) consisted of 79
      Latino consumers who met criteria for a clinical diagnosis of a psychotic
      disorder and 69 family caregivers. Participants watched a four-minute narrative
      about a woman with psychosis and were asked to identify the symptoms of serious
      mental illness (knowledge of psychosis), describe the character's problem and
      whether she had a serious mental illness (illness attribution), and offer
      suggestions about what the parents should do (help seeking). Responses to the
      open-ended questions were reliably coded by two trained raters. RESULTS:
      Consumers reported low psychosis literacy across all indices (e.g., only 8%
      included delusions in their knowledge of serious mental illness). Compared with
      consumers, caregivers reported significantly greater psychosis literacy across
      most indices, although relatively few reported knowledge of delusions (28%) and
      disorganized speech (36%). Logistic regression analyses found that caregivers
      were more than twice as likely as consumers to suggest that the parents seek
      professional help. Among both consumers and caregivers, greater knowledge of
      psychosis and attribution of symptoms to serious mental illness were associated
      with increased likelihood of recommending professional help seeking. CONCLUSIONS:
      Community campaigns and psychoeducation interventions within clinical settings
      are needed to improve psychosis literacy among Latinos with FEP. Increasing
      knowledge of psychosis and facilitating attributions of psychotic symptoms to
      serious mental illness have the potential to promote professional help seeking.

PMID- 30220246
TI  - Hypomagnesemia and hypermagnesemia.
AB  - INTRODUCTION: Magnesium is an essential element which also has pleiotropic
      effects in humans. Recent studies have altered our interpretation of a disturbed
      magnesium balance both leading to hypomagnesemia and hypermagnesemia. METHODS: a
      narrative review of their clinical relevance is presented. RESULTS: Although
      magnesium balance is strictly controlled by the kidneys, hypomagnesemia is fairly
      common, especially in people with comorbid conditions. Increased renal magnesium
      wasting, often aggravated by drugs, is commonly found in conditions associated
      with unfavorable outcomes such as diabetes mellitus and sepsis. Depending on its
      severity hypomagnesemia may reveal itself by potentially hazardous neurological
      and cardiovascular symptoms. Intravenous magnesium is an evidence-based treatment
      of torsades de pointes and preeclampsia irrespective of the presence of
      preexisting hypomagnesemia. Magnesium deficiency and/or hypomagnesemia has been
      linked to cardiovascular disease, vascular calcification and endothelial function
      both in vitro and in vivo. (Severe) hypermagnesemia can be life-threatening but
      is almost exclusively observed in patients with substantially decreased kidney
      function associated with high magnesium intake through supplements or magnesium
      containing cathartics or antacids. CONCLUSION: It remains unclear whether mild
      hypermagnesemia confers survival benefit especially in subjects with decreased
      kidney function. The role of oral magnesium supplementation of chronic mild
      asymptomatic hypomagnesemia also merits further exploration through
      interventional studies in various study populations.

PMID- 30220247
TI  - James Smithson on the Calamines: Chemical Combination in Crystals.
AB  - The three mineral species that constitute the common "calamines," or non
      sulphurous ores of zinc, were first definitively identified in 1803 by the
      British chemist and mineralogist James Smithson. The present article proposes a
      close exegesis of Smithson's argument, which has not previously been studied in
      any detail. His reasoning integrated chemical, natural historical, and
      crystallographic considerations, and illustrates important features of the
      practice of mineral chemistry at this time. Whereas zinc ore was an essential
      component of the rapidly expanding brass industry, the context for Smithson's
      work was not commercial, but rather that of mineral collecting and natural
      history. Appreciating this fact, and the role of crystallography within this
      setting, helps to shed light on the interesting theoretical speculations about
      chemical combination that he included in the paper. Smithson's ideas about
      chemical combination were informed by a structural way of thinking about
      materials, and his argument illustrates some of the ways that crystallog-raphy
      influenced chemistry in this period.

PMID- 30220248
TI  - Subnational regional inequality in the public health development index in
      Indonesia.
AB  - BACKGROUND: Achieving the Sustainable Development Goal of 'ensuring healthy lives
      and promoting well-being for all at all ages' necessitates regular monitoring of
      inequality in the availability of health-related infrastructure and access to
      services, and in health risks and outcomes. OBJECTIVES: To quantify subnational
      regional inequality in Indonesia using a composite index of public health
      infrastructure, services, behavioural risk factors and health outcomes: the
      Public Health Development Index (PHDI). METHODS: PHDI is a composite index of 30
      public health indicators from across the life course and along the continuum of
      care. An overall index and seven topic-specific sub-indices were calculated using
      data from the 2013 Indonesian Basic Health Survey (RISKESDAS) and the 2011 -
      Village Potential Survey (PODES). These indices were analysed at the national,
      province and district levels. Within-province inequality was calculated using the
      Weighted Index of Disparity (IDISW). RESULTS: National average PHDI overall index
      was 54.0 (out of a possible 100); scores differed between provinces, ranging from
      43.9 in Papua to 65.0 in Bali. Provinces in western regions of Indonesia tended
      to have higher overall PHDI scores compared to eastern regions. Large variations
      in province averages were observed for the non-communicable diseases sub-index,
      environmental health sub-index and infectious diseases sub-index. Provinces with
      a similar number of districts and with similar overall scores on the PHDI index
      showed different levels of relative within-province inequality. Greater within
      province relative inequalities were seen in the environmental health and health
      services provisions sub-indices as compared to other indices. CONCLUSIONS:
      Achieving the goal of ensuring healthy lives and promoting well-being for all at
      all ages in Indonesia necessitates having a more focused understanding of
      district-level inequalities across a wide range of public health infrastructure,
      service, risk factor and health outcomes indicators, which can enable
      geographical comparison while also revealing areas for intervention to address
      health inequalities.

PMID- 30220250
TI  - Behcet's disease; A rare refractory patient with vena cava superior syndrome
      treated with infliximab: a case report and review of the literature.
AB  - OBJECTIVES: Behcet's disease (BD) is a multi-systemic inflammatory disorder which
      can affect all types and sizes of vessels.The usage of TNF-alpha antagonists is
      increasing in different involvements of BD that is inadequately controlled by
      standard immunosuppressive regimens. METHODS: Here we reported a rare BD case
      that is controlled by only infliximab (IFX) treatment. RESULTS: A 24-years-old
      male patient was diagnosed as BD with recurrent oral and genital
      ulcerations,uveitis,femoral vein thrombosis and HLA-B5 positivity.He had had
      terminal ileitis,epididymitis,bilateral internal iliac artery aneurysm and
      superior sagittal sinus thrombosis after the diagnosis.He admitted to our
      outpatient clinic with dyspnea,orthopnea,chest pain and facial swelling.We
      detected facial edema,plethora,venous distention on neck and chest.We suspected
      vena cava superior syndrome(VCSS) and performed CT angiography that demonstrated
      high-grade vena cava superior stenosis and thrombus where SVC opens to the right
      atrium.Patient was anticoagulated with warfarin and a shunt was implanted between
      the left brachiocephalic vein and right atrium.Colchicine and interferon-alfa
      treatment were continued and 1mg/kg steroid was added.But the patients' symptoms
      relapsed one month later and his shunt was revised with balloon
      angioplasty.5mg/kg IFX was started.We  performed a CT-angiography annually for
      two years.VCSS and other symptoms of BD are resolved and have not relapsed yet.
      CONCLUSIONS: Vascular involvement of BD are generally treated with
      immunosuppressive agents such as steroids and immunomodulators.IFX was found
      effective and well tolerated in the treatment of intestinal,neurological and
      vascular involvement of BD especially in patients with poor response or
      intolerance to conventional therapy.This case report supports IFX as a new
      therapeutic option for patients with vascular BD.

PMID- 30220251
TI  - Depletion of Nesprin-2 is associated with an embryonic lethal phenotype in mice.
AB  - Nesprin-2 is a nuclear envelope component and provides a link between
      cytoskeletal components of the cytoplasm and the nucleoplasm. Several isoforms
      are generated from its gene Syne2. Loss of the largest isoform Nesprin-2 Giant in
      mice is associated with a skin phenotype and altered wound healing, loss of C
      terminal isoforms in mice leads to cardiomyopathies and neurological defects.
      Here we attempted to establish mice with an inducible knockout of all Nesprin-2
      isoforms by inserting shRNA encoding sequences targeting the N- and C-terminus
      into the ROSA26 locus of mice. This caused early embryonic death of the animals
      harboring the mutant allele, which was presumably due to leaky expression of the
      shRNAs. Mutant embryos were only observed before E13. They had an altered
      appearance and were smaller in size than their wild type littermates. From this
      we conclude that the Nesprin-2 gene function is crucial during embryonic growth,
      differentiation and organogenesis.

PMID- 30220253
TI  - The role of electrocardiogram in sex verification in a young adult with primary
      amenorrhea: a case report.
AB  - BACKGROUND: The use of electrocardiogram for sex verification in adults is an
      emerging concept in medicine. It is feasible through the utilization of Ogunlade
      Sex Determination Electrocardiographic Score. The aim of this study was to use an
      electrocardiogram to verify the sex of a woman with primary amenorrhea. CASE
      PRESENTATION: We report a case of a 36-year-old woman of Yoruba ethnicity who
      presented with primary amenorrhea. A physical examination revealed a woman with a
      feminine appearance characterized by long plaited hair and well-developed
      breasts. As part of the investigations to unravel the sex status, she had a
      resting standard 12-lead electrocardiogram which revealed a masculine
      electrocardiogram pattern with Ogunlade Sex Determination Electrocardiographic
      Score of 9 (T-wave pattern in lead V1, 3; ST segment in lead V2 or V3, 3; QRS
      rotation, 2; heart rate of 79, 1). An abdominopelvic ultrasonography done by a
      radiologist showed absence of uterus, fallopian tubes, and ovaries. When our
      patient was considered for transvaginal scan, she declined but embraced
      translabial ultrasound as she claimed to be a virgin. Translabial ultrasonography
      revealed the presence of undescended hypoplastic testes with associated
      testicular microlithiasis at the external inguinal rings bilaterally. Karyotyping
      using a blood sample revealed 46,XY and a sex-determining region Y report showed
      that the blood sample was positive for the SRY gene confirming the status as
      male. This synchronized with the initial electrocardiogram evaluation. The testes
      were later removed. CONCLUSION: This report concluded that an electrocardiogram
      as a cheap, readily available and non-invasive test has a role in sex
      verification in young adults with primary amenorrhea.

PMID- 30220252
TI  - Neural stem cells for disease modeling and evaluation of therapeutics for Tay
      Sachs disease.
AB  - BACKGROUND: Tay-Sachs disease (TSD) is a rare neurodegenerative disorder caused
      by autosomal recessive mutations in the HEXA gene on chromosome 15 that encodes
      beta-hexosaminidase. Deficiency in HEXA results in accumulation of GM2
      ganglioside, a glycosphingolipid, in lysosomes. Currently, there is no effective
      treatment for TSD. RESULTS: We generated induced pluripotent stem cells (iPSCs)
      from two TSD patient dermal fibroblast lines and further differentiated them into
      neural stem cells (NSCs). The TSD neural stem cells exhibited a disease phenotype
      of lysosomal lipid accumulation. The Tay-Sachs disease NSCs were then used to
      evaluate the therapeutic effects of enzyme replacement therapy (ERT) with
      recombinant human Hex A protein and two small molecular compounds: hydroxypropyl
      beta-cyclodextrin (HPbetaCD) and delta-tocopherol. Using this disease model, we
      observed reduction of lipid accumulation by employing enzyme replacement therapy
      as well as by the use of HPbetaCD and delta-tocopherol. CONCLUSION: Our results
      demonstrate that the Tay-Sachs disease NSCs possess the characteristic phenotype
      to serve as a cell-based disease model for study of the disease pathogenesis and
      evaluation of drug efficacy. The enzyme replacement therapy with recombinant Hex
      A protein and two small molecules (cyclodextrin and tocopherol) significantly
      ameliorated lipid accumulation in the Tay-Sachs disease cell model.

PMID- 30220254
TI  - Three-dimensional free breathing whole heart cardiovascular magnetic resonance T1
      mapping at 3 T.
AB  - BACKGROUND: This study demonstrates a three-dimensional (3D) free-breathing
      native myocardial T1 mapping sequence at 3 T. METHODS: The proposed sequence
      acquires three differently T1-weighted volumes. The first two volumes receive a
      saturation pre-pulse with different recovery time. The third volume is acquired
      without magnetization preparation and after a significant recovery time.
      Respiratory navigator gating and volume-interleaved acquisition are adopted to
      mitigate misregistration. The proposed sequence was validated through simulation,
      phantom experiments and in vivo experiments in 12 healthy adult subjects.
      RESULTS: In phantoms, good agreement on T1 measurement was achieved between the
      proposed sequence and the reference inversion recovery spin echo sequence (R2 =
      0.99). Homogeneous 3D T1 maps were obtained from healthy adult subjects, with a
      T1 value of 1476 +/- 53 ms and a coefficient of variation (CV) of 6.1 +/- 1.4%
      over the whole left-ventricular myocardium. The averaged septal T1 was 1512 +/-
      60 ms with a CV of 2.1 +/- 0.5%. CONCLUSION: Free-breathing 3D native T1 mapping
      at 3 T is feasible and may be applicable in myocardial assessment. The proposed
      3D T1 mapping sequence is suitable for applications in which larger coverage is
      desired beyond that available with single-shot parametric mapping, or breath
      holding is unfeasible.

PMID- 30220255
TI  - Impact of preventive primary care on children's unplanned hospital admissions: a
      population-based birth cohort study of UK children 2000-2013.
AB  - BACKGROUND: Universal health coverage (UHC) aims to improve child health through
      preventive primary care and vaccine coverage. Yet, in many developed countries
      with UHC, unplanned and ambulatory care sensitive (ACS) hospital admissions in
      childhood continue to rise. We investigated the relation between preventive
      primary care and risk of unplanned and ACS admission in children in a high-income
      country with UHC. METHODS: We followed 319,780 children registered from birth
      with 363 English practices in Clinical Practice Research Datalink linked to
      Hospital Episodes Statistics, born between January 2000 and March 2013. We used
      Cox regression estimating adjusted hazard ratios (HR) to examine subsequent risk
      of unplanned and ACS hospital admissions in children who received preventive
      primary care (development checks and vaccinations), compared with those who did
      not. RESULTS: Overall, 98% of children had complete vaccinations and 87% had
      development checks. Unplanned admission rates were 259, 105 and 42 per 1000 child
      years in infants (aged < 1 year), preschool (1-4 years) and primary school (5-9
      years) children, respectively. Lack of preventive care was associated with more
      unplanned admissions. Infants with incomplete vaccination had increased risk for
      all unplanned admissions (HR 1.89, 1.79-2.00) and vaccine-preventable admissions
      (HR 4.41, 2.59-7.49). Infants lacking development checks had higher risk for
      unplanned admission (HR 4.63, 4.55-4.71). These associations persisted across
      childhood. Children who had higher consulting rates with primary care providers
      also had higher risk of unplanned admission (preschool children: HR 1.17, 1.17
      1.17). One third of all unplanned admissions (62,154/183,530) were for ACS
      infectious illness. Children with chronic ACS conditions, asthma, diabetes or
      epilepsy had increased risk of unplanned admission (HR 1.90, 1.77-2.04, HR 11.43,
      8.48-15.39, and HR 4.82, 3.93-5.91, respectively). These associations were
      modified in children who consulted more in primary care. CONCLUSIONS: A high
      uptake of preventive primary care from birth is associated with fewer unplanned
      and ACS admissions in children. However, the clustering of poor health, a lack of
      preventive care uptake, and social deprivation puts some children with comorbid
      conditions at very high risk of admission. Strengthening immunisation coverage
      and preventive primary care in countries with poor UHC could potentially
      significantly reduce the health burden from hospital admission in children.

PMID- 30220256
TI  - Cryopreservation of collared peccary (Pecari tajacu L., 1758) epididymal sperm
      using extenders based on Tris and powdered coconut water (ACP(r)-116c).
AB  - SummaryThe aim of this study was to establish a functional freezing-thawing
      protocol for epididymal sperm of collared peccaries (Pecari tajacu L., 1758) by
      comparing different extenders. The epididymal sperm from 12 sexually mature males
      was recovered by retrograde flushing using Tris-based or coconut water-based
      (ACP(r)-116c) extenders. After initial evaluation, samples were diluted and
      frozen with the same extenders to which 20% egg yolk and 6% glycerol were added.
      After 2 weeks, thawing was performed at 37 degrees C/60 s and sperm motility,
      vigour, morphology, functional membrane integrity, sperm viability, sperm plasma
      membrane integrity, and a computer-assisted semen analysis (CASA) were assessed.
      In addition, to evaluate the survival of frozen-thawed sperm, a thermal
      resistance test (TRT) was executed. Samples preserved using Tris were in better
      condition compared with those preserved using ACP(r), showing higher values for
      most assessments performed, including CASA and the TRT (P<0.05). After
      determining Tris to be the better of the two extenders, additional samples were
      thawed using different thawing rates (37 degrees C/60 s, 55 degrees C/7 s, 70
      degrees C/8 s). Sperm thawed at 37 degrees C/60 s had the greatest preservation
      (P<0.05) of viability (54.1 +/- 5.9%) and functional membrane integrity (43.2 +/-
      5.4%), and had higher values for various CASA parameters. In conclusion, we
      suggest the use of a Tris-based extender added to egg yolk and glycerol for the
      cryopreservation of epididymal sperm obtained from collared peccaries. In order
      to achieve better post-thawing sperm quality, we suggest that samples should be
      thawed at 37 degrees C/60 s.

PMID- 30220257
TI  - Letter to Editor in response to: Potential confounding in a study of dietary
      inflammatory index and cognitive function.

PMID- 30220258
TI  - Enhancing Reporting of After Action Reviews of Public Health Emergencies to
      Strengthen Preparedness: A Literature Review and Methodology Appraisal.
AB  - OBJECTIVE: This literature review aimed to identify the range of methods used in
      after action reviews (AARs) of public health emergencies and to develop appraisal
      tools to compare methodological reporting and validity standards. METHODS: A
      review of biomedical and gray literature identified key approaches from AAR
      methodological research, real-world AARs, and AAR reporting templates. We
      developed a 50-item tool to systematically document AAR methodological reporting
      and a linked 11-item summary tool to document validity. Both tools were used
      sequentially to appraise the literature included in this study. RESULTS: This
      review included 24 highly diverse papers, reflecting the lack of a standardized
      approach. We observed significant divergence between the standards described in
      AAR and qualitative research literature, and real-world AAR practice. The lack of
      reporting of basic methods to ensure validity increases doubt about the
      methodological basis of an individual AAR and the validity of its conclusions.
      CONCLUSIONS: The main limitations in current AAR methodology and reporting
      standards may be addressed through our 11 validity-enhancing recommendations. A
      minimum reporting standard for AARs could help ensure that findings are valid and
      clear for others to learn from. A registry of AARs, based on a common reporting
      structure, may further facilitate shared learning. (Disaster Med Public Health
      Preparedness. 2018;page 1 of 8).

PMID- 30220259
TI  - Combined influence of depressive symptoms and systemic inflammation on all-cause
      and cardiovascular mortality: evidence for differential effects by gender in the
      English Longitudinal Study of Ageing.
AB  - BACKGROUND: Depressive symptoms and inflammation are risk factors for
      cardiovascular disease (CVD) and mortality. We investigated the combined
      association of these factors with the prediction of CVD and all-cause mortality
      in a representative cohort of older men and women. METHODS: We measured C
      reactive protein (CRP) and depressive symptoms in 5328 men and women aged 52-89
      years in the English Longitudinal Study of Ageing. Depressive symptoms were
      measured using the eight-item Centre for Epidemiological Studies Depression
      Scale. CRP was analysed from peripheral blood. Mortality was ascertained from
      national registers and associations with depressive symptoms and inflammation
      were estimated using Cox proportional hazard models. RESULTS: We identified 112
      CVD related deaths out of 420 all-cause deaths in men and 109 CVD related deaths
      out of 334 all-cause deaths in women over a mean follow-up of 7.7 years. Men with
      both depressive symptoms and high CRP (3-20 mg/L) had an increased risk of CVD
      mortality (hazard ratio; 95% confidence interval: 3.89; 2.04-7.44) and all-cause
      mortality (2.40; 1.65-3.48) after adjusting for age, socioeconomic variables and
      health behaviours. This considerably exceeds the risks associated with high CRP
      alone (CVD 2.43; 1.59-3.71, all-cause 1.49; 1.20-1.84). There was no significant
      increase in mortality risk associated with depressive symptoms alone in men. In
      women, neither depressive symptoms or inflammation alone or the combination of
      both significantly predicted CVD or all-cause mortality. CONCLUSIONS: The
      combination of depressive symptoms and increased inflammation confers a
      considerable increase in CVD mortality risk for men. These effects appear to be
      independent, suggesting an additive role.

PMID- 30220260
TI  - Effects of human sperm cryopreservation on apoptotic markers in normozoospermic
      and non-normozoospermic patients.
AB  - SummaryThe negative effects of cryopreservation on sperm parameters are well
      documented but little information is known about molecular basis of the process.
      The aim of the present study was to investigate the possible effects of sperm
      cryopreservation on main apoptotic signs including DNA fragmentation and caspase
      3 activation and to determine if these effects vary according to sperm
      parameters. Sperm samples of 72 patients were cryopreserved. The patients were
      sub-grouped as normozoospermic or non-normozoospermic patients according to their
      semen parameters. DNA fragmentation rates and caspase-3 activation levels were
      analyzed before and after cryopreservation in both groups. Mean DNA fragmentation
      rate was increased significantly from 23.98% in neat semen samples to 27.34%
      after cryopreservation (P = 0.03). DNA fragmentation rates were slightly higher
      in non-normozoospermic patients compared with the normozoospermic patients in
      both the neat semen and after cryopreservation (23.25 and 24.71% vs. 26.32 and
      28.36%, respectively) although the difference obtained were not statistically
      significant. An increasing trend for caspase-3 activations (0.093 vs. 0.116) was
      observed after cryopreservation but the differences were not statistically
      significant. Caspase-3 activation was found to be slightly higher in non
      normozoospermic patients both in the neat semen and after cryopreservation
      compared with the normozoospermic patients but the differences were not
      statistically significant. Caspase-3 expression was also shown using
      immunocytochemistry in both fresh ejaculated sperm and thawed sperm after
      cryopreservation but at different localizations. The cryopreservation process had
      detrimental effects on sperm quality but the quality of the sperm samples was not
      adversely effective for the apoptotic markers including DNA fragmentation and
      caspase-3 activation patterns. In fact, it was the cryopreservation process
      itself that adversely effected the above apoptotic markers and apoptosis. It was
      concluded therefore that sperm cell cryopreservation triggers apoptosis after
      thawing and this process adversely affects semen parameters.

PMID- 30220261
TI  - The pattern of symptom change during prolonged exposure therapy and present
      centered therapy for PTSD in active duty military personnel.
AB  - BACKGROUND: Few studies have investigated the patterns of posttraumatic stress
      disorder (PTSD) symptom change in prolonged exposure (PE) therapy. In this study,
      we aimed to understand the patterns of PTSD symptom change in both PE and present
      centered therapy (PCT). METHODS: Participants were active duty military personnel
      (N = 326, 89.3% male, 61.2% white, 32.5 years old) randomized to spaced-PE (S-PE;
      10 sessions over 8 weeks), PCT (10 sessions over 8 weeks), or massed-PE (M-PE; 10
      sessions over 2 weeks). Using latent profile analysis, we determined the optimal
      number of PTSD symptom change classes over time and analyzed whether baseline and
      follow-up variables were associated with class membership. RESULTS: Five classes,
      namely rapid responder (7-17%), steep linear responder (14-22%), gradual
      responder (30-34%), non-responder (27-33%), and symptom exacerbation (7-13%)
      classes, characterized each treatment. No baseline clinical characteristics
      predicted class membership for S-PE and M-PE; in PCT, more negative baseline
      trauma cognitions predicted membership in the non-responder v. gradual responder
      class. Class membership was robustly associated with PTSD, trauma cognitions, and
      depression up to 6 months after treatment for both S-PE and M-PE but not for PCT.
      CONCLUSIONS: Distinct profiles of treatment response emerged that were similar
      across interventions. By and large, no baseline variables predicted responder
      class. Responder status was a strong predictor of future symptom severity for PE,
      whereas response to PCT was not as strongly associated with future symptoms.

PMID- 30220262
TI  - Sperm abnormalities in matrinxa Brycon amazonicus after hormonal treatment with
      carp pituitary extract and OvaprimTM.
AB  - SummaryThe aim of this study was to evaluate if hormonal treatment causes changes
      in the morphology of matrinxa Brycon amazonicus spermatozoa. Twelve males were
      randomized into three treatment groups: 1, OvaprimTM (0.5 ml/kg); 2, carp
      pituitary extract (CPE; 2.0 mg/kg); and 3, NaCl solution 0.9% - control group
      (0.5 ml/kg); with four replicates. Morphological sperm analysis was performed
      using an optical and scanning electron microscope. The percentage of normal
      spermatozoa (49.6+/-4.6% to 60.8+/-2.8%), with primary (26.1+/-6.4% to 45.3+/
      4.5%) and secondary abnormalities (4.4+/-2.9% to 13.9+/-3.5%) did not differ
      significantly between treatment groups. There were no significant differences
      between treatments in relation to the primary abnormalities found in the head
      (10.5+/-3.8% to 25.5+/-6.3%), the midpiece (0.1+/-0.1% to 0.2+/-0.2%) and in the
      flagellum (18.9+/-3.8% to 15.5+/-3.1%), as well as in the secondary
      abnormalities, located in the head (0.8+/-0.4% to 7.8+/-4.6%) and in the
      flagellum (2.2+/-1.1% to 6.1+/-1.5%). When each abnormality was evaluated
      individually, only the percentage of degenerated head was higher in the CPE
      induced group (24.9+/-5.9%) than the control group (7.2+/-3.1%). We concluded
      that the use of pituitary extract of carp or OvaprimTM under the conditions of
      this experiment does not influence the percentage of sperm abnormalities in B.
      amazonicus.

PMID- 30220263
TI  - Early change in reward and punishment sensitivity as a predictor of response to
      antidepressant treatment for major depressive disorder: a CAN-BIND-1 report.
AB  - BACKGROUND: In an effort to optimize patient outcomes, considerable attention is
      being devoted to identifying patient characteristics associated with major
      depressive disorder (MDD) and its responsiveness to treatment. In the current
      study, we extend this work by evaluating whether early change in these
      sensitivities is associated with response to antidepressant treatment for MDD.
      METHODS: Participants included 210 patients with MDD who were treated with 8
      weeks of escitalopram and 112 healthy comparison participants. Of the original
      210 patients, 90 non-responders received adjunctive aripiprazole for an
      additional 8 weeks. Symptoms of depression and anhedonia were assessed at the
      beginning of treatment and 8 weeks later in both samples. Reward and punishment
      sensitivity were assessed using the BIS/BAS scales measured at the initiation of
      treatment and 2 weeks later. RESULTS: Individuals with MDD exhibited higher
      punishment sensitivity and lower reward sensitivity compared with healthy
      comparison participants. Change in reward sensitivity during the first 2 weeks of
      treatment was associated with improved depressive symptoms and anhedonia
      following 8 weeks of treatment with escitalopram. Similarly, improvement in
      reward responsiveness during the first 2 weeks of adjunctive therapy with
      aripiprazole was associated with fewer symptoms of depression at post-treatment.
      CONCLUSIONS: Findings highlight the predictive utility of early change in reward
      sensitivity during antidepressant treatment for major depression. In a clinical
      setting, a lack of change in early reward processing may signal a need to modify
      a patient's treatment plan with alternative or augmented treatment approaches.

PMID- 30220264
TI  - Metacommunity structure of the helminths of the black-eared opossum Didelphis
      aurita in peri-urban, sylvatic and rural environments in south-eastern Brazil.
AB  - Among the Brazilian marsupials, the species of the genus Didelphis are the most
      parasitized by helminths. This study aimed to describe the species composition
      and to analyse the helminth communities of the Atlantic Forest common opossum
      Didelphis aurita at infracommunity and component community levels using the
      Elements of Metacommunity Structure Analysis, considering peri-urban, sylvatic
      and rural environments in the state of Rio de Janeiro, Brazil. Seventy-three
      specimens of D. aurita were captured during the study. Fourteen species of
      helminths were collected: nine of the phylum Nematoda (Trichuris minuta,
      Trichuris didelphis, Globocephalus marsupialis, Heterostrongylus
      heterostrongylus, Travassostrongylus orloffi, Viannaia hamata, Aspidodera
      raillieti, Cruzia tentaculata and Turgida turgida); four of the phylum
      Platyhelminthes (three species of Trematoda, Duboisiella proloba, Brachylaima
      advena and Rhopalias coronatus, and one species of the class Cestoda); and one
      species of the phylum Acanthocephala (Oligacanthorhynchus microcephalus). More
      than 95% of the animals were infected with parasites. The most abundant parasite
      species were V. hamata, T. turgida, C. tentaculata and T. orloffi. The nematodes
      T. turgida, C. tentaculata and A. raillieti were the most dominant species in the
      three environments. The analysis of the metacommunity structure indicated a
      structured pattern as a function of the environmental gradient, but only when all
      localities were considered together. At the infracommunity and component
      community levels, quasi-nested and nested structures with stochastic species loss
      were observed, respectively. The results indicate that the settlement of helminth
      species in the opossums can be attributed to the heterogeneity among individual
      hosts in relation to their exposure to parasites and to extrinsic factors, which
      vary among habitats, considering a regional scale. On a local scale, the
      characteristics of this host species may promote homogenization among individual
      hosts in terms of their exposure to the helminths. This study constitutes a new
      host record for the species G. marsupialis and T. didelphis and represents a
      pioneering investigation of the helminth metacommunity of a Neotropical
      marsupial.

PMID- 30220265
TI  - Eighteen years of paediatric extracorporeal membrane oxygenation and ventricular
      assist devices: insight regarding late outcomes.
AB  - BACKGROUND: We reviewed all patients who were supported with extracorporeal
      membrane oxygenation and/or ventricular assist device at our institution in order
      to describe diagnostic characteristics and assess mortality. METHODS: A
      retrospective cohort study was performed including all patients supported with
      extracorporeal membrane oxygenation and/or ventricular assist device from our
      first case (8 October, 1998) through 25 July, 2016. The primary outcome of
      interest was mortality, which was modelled by the Kaplan-Meier method. RESULTS: A
      total of 223 patients underwent 241 extracorporeal membrane oxygenation runs.
      Median support time was 4.0 days, ranging from 0.04 to 55.8 days, with a mean of
      6.4+/-7.0 days. Mean (+/-SD) age at initiation was 727.4 days (+/-146.9 days).
      Indications for extracorporeal membrane oxygenation were stratified by primary
      indication: cardiac extracorporeal membrane oxygenation (n=175; 72.6%) or
      respiratory extracorporeal membrane oxygenation (n=66; 27.4%). The most frequent
      diagnosis for cardiac extracorporeal membrane oxygenation patients was
      hypoplastic left heart syndrome or hypoplastic left heart syndrome-related
      malformation (n=55 patients with HLHS who underwent 64 extracorporeal membrane
      oxygenation runs). For respiratory extracorporeal membrane oxygenation, the most
      frequent diagnosis was congenital diaphragmatic hernia (n=22). A total of 24
      patients underwent 26 ventricular assist device runs. Median support time was 7
      days, ranging from 0 to 75 days, with a mean of 15.3+/-18.8 days. Mean age at
      initiation of ventricular assist device was 2530.8+/-660.2 days (6.93+/-1.81
      years). Cardiomyopathy/myocarditis was the most frequent indication for
      ventricular assist device placement (n=14; 53.8%). Survival to discharge was
      42.2% for extracorporeal membrane oxygenation patients and 54.2% for ventricular
      assist device patients. Kaplan-Meier 1-year survival was as follows: all
      patients, 41.0%; extracorporeal membrane oxygenation patients, 41.0%; and
      ventricular assist device patients, 43.2%. Kaplan-Meier 5-year survival was as
      follows: all patients, 39.7%; extracorporeal membrane oxygenation patients,
      39.7%; and ventricular assist device patients, 43.2%. CONCLUSIONS: This single
      institutional 18-year review documents the differential probability of survival
      for various sub-groups of patients who require support with extracorporeal
      membrane oxygenation or ventricular assist device. The indication for mechanical
      circulatory support, underlying diagnosis, age, and setting in which cannulation
      occurs may affect survival after extracorporeal membrane oxygenation and
      ventricular assist device. The Kaplan-Meier analyses in this study demonstrate
      that patients who survive to hospital discharge have an excellent chance of
      longer-term survival.

PMID- 30220267
TI  - Relationship between nutritional status and the systemic inflammatory response:
      micronutrients.
AB  - Micronutrients such as trace elements and vitamins are important as enzyme
      cofactors in the metabolism of all cells in the body and therefore key to
      determining nutritional status. The present systematic review examined the
      evidence of the impact of the systemic inflammatory response on plasma
      micronutrient status in acute (surgical) and chronic tissue injury. A literature
      review using targeted subject headings was carried out. Plasma C-reactive protein
      was used to classify minor (80 mg/l) inflammation. The literature search produced
      2344 publications and plasma vitamin D, zinc and carotenoids were most commonly
      studied and plasma vitamins K, B2 and B6 were least studied. In acute injury
      thirteen studies (all prospective) and in chronic injury twenty-four studies
      (largely retrospective) were included in the review. There was consistent
      evidence that most common measured micronutrients in the plasma (zinc, selenium,
      vitamins A, D, E, K, B2, B6, B12, C, lutein, lycopene, alpha- and beta-carotene)
      were significantly lowered from minor to moderate to major inflammation. The
      results of the present systematic review indicate that most plasma micronutrients
      fall as part of the systemic inflammatory response irrespective of acute or
      chronic injury. Therefore, in the presence of a systemic inflammation, plasma
      micronutrient concentrations should be interpreted with caution. There are a
      number of methods applied to adjust plasma micronutrient concentrations to avoid
      misdiagnosis of deficiency. Alternatively, intracellular measurements appear to
      obviate the need for such plasma adjustment to assess micronutrient status.

PMID- 30220266
TI  - Attention-deficit/hyperactivity disorder and clinically diagnosed obesity in
      adolescence and young adulthood: a register-based study in Sweden.
AB  - BACKGROUND: A recent family study of young adult males suggests a shared familial
      liability between attention-deficit/hyperactivity disorder (ADHD) and high body
      mass index (BMI), and a genome-wide meta-analysis reported a genetic correlation
      of 0.26 between ADHD and BMI. To date, it is unclear whether these findings
      generalize to the relationship between ADHD and clinically diagnosed obesity.
      METHOD: By linking the Swedish national registers, we identified 25 38 127
      individuals born between 1973 and 2000, together with their siblings and cousins.
      The risk of clinical obesity in individuals with ADHD was compared with the risk
      in those without ADHD. The relative contributions of genetic and environmental
      factors to the association between ADHD and clinical obesity were examined via
      assessment of the familial co-aggregation of the two conditions and quantitative
      genetic analysis. RESULTS: Individuals with ADHD were at an increased risk of
      clinical obesity compared with those without (risk difference 3.73%, 95%
      confidence interval (CI) 3.55-3.90%; risk ratio 3.05, 95% CI 2.95-3.15). Familial
      co-aggregation of ADHD and clinical obesity was detected and the strength of the
      co-aggregation decreased by decreasing genetic relatedness. The correlation
      between the liabilities to ADHD and clinical obesity can be entirely attributed
      to their genetic correlation (rg 0.30, 95% CI 0.17-0.44). CONCLUSION: The
      association between ADHD and clinical obesity in adolescence and young adulthood
      can be entirely attributed to genetic underpinnings shared by the two conditions.
      Children with ADHD should be monitored for weight gain so that preventive
      measures can be taken for those on a suboptimal trajectory.

PMID- 30220268
TI  - Wisdom of the Crowd in Saving Lives: The Life Guardians App.
AB  - Multi-casualty incidents (MCIs) continue to occur throughout the world, whether
      they be mass shootings or natural disasters. Prehospital emergency services have
      done a professional job at stabilizing and transporting the victims to local
      hospitals. When there are multiple casualties, there may not be enough
      professional responders to care for the injured. Bystanders and organized
      volunteer first responders have often helped in extricating the victims, stopping
      the bleeding, and aiding in the evacuation of the victims. Magen David Adom (MDA
      translated as "Red Shield of David"), the national Emergency Medical Services
      (EMS) provider for Israel, has successfully introduced a program for volunteer
      first responders that includes both a mobile-phone-based application and
      appropriate life-saving equipment. Most of the responders, known as Life
      Guardians, are already medical professionals such as physicians, nurses, or off
      duty medics. They are notified by a global positioning system application if
      there is a nearby life-threatening incident such as respiratory or cardiac
      arrest, major trauma, or an MCI. They are given a kit that includes a bag-valve
      mask device, oropharyngeal airways, tourniquets, and bandages. There are
      currently 17,000 Life Guardians, and in the first-half of 2017, they responded to
      253 events.The Life Guardians are essentially an out-of-hospital manpower
      multiplier using a simple crowdsourcing application who have the necessary skills
      and equipment to treat those in cardiopulmonary arrest, or victims of trauma,
      including MCIs. Such a model can be integrated into other systems throughout the
      world to save lives. JaffeE, DadonZ, AlpertEA. Wisdom of the crowd in saving
      lives: the Life Guardians app. Prehosp Disaster Med. 2018;33(5):550-552.

PMID- 30220269
TI  - What do we learn from comparing ethnic-specific and WHO child growth references?

PMID- 30220270
TI  - [Consensus of early enteral nutrition clinical practice in critically ill
      patients].
AB  - OBJECTIVE: The benefits of early enteral nutrition (EEN) during critical illness
      have been widely accepted by global experts. To popularize this new concept and
      provide standardized, reasonable and effective EEN therapy for critically ill
      patients in China, more than 20 experts from throughout the country discussed and
      developed this consensus. We used the GRADE approach for consensus development,
      focusing on important clinical issues such as nutrition assessment, initiating
      mode, route selection and tolerance monitoring of EEN support therapy for current
      critically ill patients. This consensus would be certainly help for intensive
      care physicians in the clinical application of EEN support therapy for critically
      ill patients.

PMID- 30220271
TI  - [Prognostic value of differences between peripheral arterial and venous blood gas
      analysis in patients with septic shock].
AB  - OBJECTIVE: To investigate the value of the difference between peripheral arterial
      and venous blood gas analysis for the prognosis of patients with septic shock
      after resuscitation. METHODS: Patients with septic shock aged 18 to 80 years
      admitted to intensive care unit (ICU) of Affiliated Hospital of Integrated
      Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine
      from May 2016 to December 2017 were enrolled. The peripheral arterial blood and
      peripheral venous blood gas analysis were measured simultaneously after the early
      6 hours resuscitation, including pH, partial pressure of oxygen (PO2), partial
      pressure of carbon dioxide (PCO2), base excess (BE), bicarbonate (HCO3-) and
      lactate (Lac) level, and the difference values between peripheral arterial and
      venous blood were calculated. According to the 28-day survival, the patients were
      divided into survival group and death group. Multiple Logistic regression
      analysis was used to analyze the risk factors of death, and the receiver
      operating characteristic curve (ROC) was used to analyze the prognostic value of
      blood gas analysis parameters for prognosis. RESULTS: A total of 65 patients with
      septic shock resuscitation were enrolled in the study, 35 survived while 30 died
      during the 28-day period. (1) There was no significant difference in gender, age,
      and mean arterial pressure (MAP), central venous pressure (CVP), central venous
      oxygen saturation (ScvO2) and norepinephrine (NE) dose between the two groups.
      (2) The arterial and venous Lac, the difference of Lac (DeltaLac) and PCO2
      (DeltaPCO2) between arterial and venous blood in death group were significantly
      higher than those in survival group [arterial Lac (mmol/L): 7.40+/-3.10 vs.
      4.82+/-2.91, venous Lac (mmol/L): 9.17+/-3.27 vs. 5.81+/-3.29, DeltaLac (mmol/L):
      1.77+/-0.54 vs. 0.99+/-0.60, DeltaPCO2 (mmHg, 1 mmHg = 0.133 kPa): 9.64+/-5.08
      vs. 6.70+/-3.71, all P < 0.01], and there was no significant difference in the
      other arterial and venous blood gas analysis index and its corresponding
      differential difference between two groups. (3) Multiple Logistic regression
      analysis showed that DeltaPCO2 [beta = 0.247, odd ratio (OR) = 1.280, 95%
      confidential interval (95%CI) = 1.057-1.550, P = 0.011], and DeltaLac (beta =
      2.696, OR = 14.820, 95%CI = 2.916-75.324, P = 0.001) were the independent risk
      factors for the prognosis of septic shock. (4) It was shown by ROC curve analysis
      that arterial blood Lac, DeltaLac and DeltaPCO2 had predictive value on prognosis
      of septic shock, the area under ROC curve (AUC) was 0.792, 0.857, 0.680,
      respectively (all P < 0.05). When the best cut-off value of arterial Lac was 4.00
      mmol/L, the sensitivity was 100%, and the specificity was 62.86% for predictor of
      death in 28-day; when the best cut-off value of DeltaLac was 1.25 mmol/L, the
      sensitivity was 93.33%, and the specificity was 68.57% for predictor of death in
      28-day; when the best cut-off value of DeltaPCO2 was 4.35 mmHg, the sensitivity
      was 83.33%, and the specificity was 37.14% for predictor of death in 28-day.
      CONCLUSIONS: Compared to other parameters, the difference between peripheral
      arterial and venous blood gas analysis, DeltaPCO2 and DeltaLac had the best
      correlation with the prognosis of septic shock. The DeltaPCO2 and DeltaLac are
      the independent prognostic predictors for 28-day survival.

PMID- 30220272
TI  - [Predictive value of central venous-to-arterial carbon dioxide difference on the
      prognosis of elderly patients with sepsis].
AB  - OBJECTIVE: To investigate the predictive value of central venous-to-arterial
      carbon dioxide difference (Pcv-aCO2) on the prognosis of elderly patients with
      sepsis. METHODS: 208 elderly patients who met the diagnostic criteria of the
      Sepsis-3 and with the age of more than 60 years old, and admitted to intensive
      care unit (ICU) of Guangdong General Hospital from January to December in 2017
      were enrolled. According to the prognosis, the patients were divided into death
      group (n = 46) and survival group (n = 162). The Pcv-aCO2, central venous oxygen
      saturation (ScvO2), serum procalcitonin (PCT), C-reactive protein (CRP),
      sequential organ failure assessment (SOFA) and acute physiology and chronic
      health evaluation II (APACHE II) were collected for all patients. The differences
      of each index between the two groups were compared. The correlations between Pcv
      aCO2 and ScvO2, PCT, CRP, SOFA, APACHE II scores were analyzed respectively with
      Pearson correlation. The prognostic value of Pcv-aCO2 in elderly patients with
      sepsis was assessed by receiver operating characteristic curve (ROC). RESULTS:
      Compared with survival group, the Pcv-aCO2, PCT, CRP, SOFA and APACHE II scores
      in death group were significantly increased [Pcv-aCO2 (mmHg, 1 mmHg = 0.133 kPa):
      6.13+/-3.33 vs. 4.40+/-2.65, PCT (MUg/L): 31.41+/-12.83 vs. 3.01+/-2.69, CRP
      (mg/L): 130.51+/-42.23 vs. 104.46+/-50.12, SOFA: 12.01+/-2.25 vs. 9.05+/-2.06,
      APACHE II: 29.52+/-5.03 vs. 20.01+/-3.21, all P < 0.05], and ScvO2 in death group
      was significantly decreased (0.571+/-0.136 vs. 0.685+/-0.106, P < 0.01).
      Correlation analysis showed that the Pcv-aCO2 was negatively correlated with
      ScvO2 (r = -0.762, P = 0.001) and was positively correlated with PCT, CRP, SOFA
      and APACHE II scores (r value was 0.737, 0.625, 0.738, 0.713, respectively, all P
      < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of Pcv
      aCO2 prediction of death in patients with sepsis was 0.826, the cut-off was 6.62
      mmHg, the sensitivity was 84.7%, the specificity was 77.5%, the positive
      likelihood ratio was 3.76, and the negative likelihood ratio was 0.19.
      CONCLUSIONS: Pcv-aCO2 has a great value in evaluating the prognosis of elderly
      patients with sepsis and can accurately determine the prognosis of sepsis.

PMID- 30220273
TI  - [Mormorphological and functional changes of lung cells in hyperoxia environment].
AB  - OBJECTIVE: To observe the morphological and functional changes of different lung
      cells in hyperoxia environment. METHODS: Type II alveolar epithelial cells (AEC
      II) and lung fibroblasts (LFs) of fetal rats with 18 days old were isolated and
      cultured in vitro, and divided into air group (placed in an atmospheric
      incubator, and culturing with oxygen volume fraction of 0.21) and hyperoxia group
      (placed in a high oxygen culture chamber, and culturing with oxygen volume
      fraction of 0.90). Morphological changes of two kinds of cells were observed
      under microscope. Cell migration was observed by scratch test. The levels of
      reactive oxygen species (ROS) and apoptosis in cells were detected by flow
      cytometry. RESULTS: After 8 hours of hyperoxia, the volume of AEC II increased
      and the cells were loosely arranged; the clearance of LFs cells was increased and
      arranged in disorder. Scratch test showed that, compared with air group, the
      immigration rate of AEC II was inhibited at 6 hours hyperoxia [migration rate:
      (38.67+/-1.15)% vs. (58.67+/-2.31)%, P < 0.01], the immigration rate of LFs was
      promoted at 12 hours after hyperoxia [migration rate: (55.37+/-1.50)% vs.
      (46.90+/-1.20)%, P < 0.01]. With the increase of hyperoxia time, intracellular
      ROS contents of two cells were gradually increased, which were significantly
      higher than those of the air group (fluorescence intensity: 130.67+/-4.04 vs.
      54.67+/-2.51, 85.00+/-2.00 vs. 60.33+/-1.52, both P < 0.01). Both two kinds of
      cells showed apoptosis after exposure to high oxygen, the apoptosis rate of AEC
      II at 2 hour exposure were significantly higher than that of air group [(1.93+/
      0.28)% vs. (1.07+/-0.11)%, P < 0.05], the apoptosis rate of LFs at 6 hour
      exposure was significantly higher than that of air group [(1.66+/-0.09)% vs.
      (1.46+/-0.09)%, P < 0.05]. CONCLUSIONS: High concentration of oxygen can cause
      poor growth of lung cells, reduce AEC II migration level and increase LFs
      migration, and the production of intracellular ROS eventually leads to apoptosis
      of lung cells.

PMID- 30220274
TI  - [Protective effect of microRNA-155 antisense oligonucleotid on lipopolysaccharide
      induced acute lung injury in mice].
AB  - OBJECTIVE: To investigate the protective effect of microRNA-155 (miR-155)
      antisense oligonucleotid (ASO) on acute lung injury (ALI) mice by establishing a
      lentiviral expression vector of ASO of miRNA. METHODS: miR-155 antisense
      oligonucleotides amplified by polymerase chain reaction (PCR) from genomic, using
      BamH I and Nhe I double digestion, ligated into lentiviral expression vector.
      Sequence and virus titer were measured. According to the random number table
      method, 54 male BALB/c mice of 4-6 weeks old were divided into three groups. ALI
      animal models were prepared by intraperitoneal injection of 10 mg/kg
      lipopolysaccharide (LPS). The three groups were injected with 200 MUL phosphate
      buffered saline (PBS) containing 1*108/mL pmiR-155-ASO virus (pmiR-155-ASO group)
      or 200 MUL PBS containing 1*108/mL pSMPUW-miR-GFP empty virus (pmiR-cont group)
      or the same amount of PBS (PBS group) at 24 hours before the molding. Ten mice in
      each group were used to observe the 7-day survival rate. Blood samples and lung
      tissues of the remaining 8 mice were harvested after the model was established,
      and the levels of serum inflammatory cytokines were determined by enzyme linked
      immunosorbent assay (ELISA); the expression of miR-155 in lung tissue was
      detected by real-time reverse transcription-polymerase chain reaction (RT-PCR);
      histopathological changes of lung and distribution of macrophages were observed
      under microscope. RESULTS: There was no significant difference in each index
      between pmiR-cont group and PBS group. The mature miR-155 expression in lung
      tissue in pmiR-155-ASO group was significantly lower than that in pmiR-cont group
      (2-DeltaDeltaCt: 4.92+/-0.72 vs. 15.38+/-0.60, P < 0.05). Compared with pmiR-cont
      group, the injury degree of ALI mice after pretreatment with miR-155 ASO was
      significantly improved, and the 7-day survival rate was significantly increased
      (72.1% vs. 61.9%, P < 0.05 ); gross lung observation showed that congestion in
      lung tissue was significantly reduced, and the ratio of wet/dry weight (W/D) of
      lung was significantly decreased (4.50+/-0.13 vs. 5.64+/-0.61, P < 0.05);
      hematoxylin-eosin (HE) staining showed that inflammatory cell infiltration in
      lung tissue was decreased, while immunofluorescence assay showed that macrophage
      infiltration in lung tissue was significant decreased; the levels of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in serum were
      significantly decreased [TNF-alpha (ng/L): 379.8+/-48.9 vs. 495.9+/-33.3, IL-6
      (ng/L): 262.3+/-61.8 vs. 355.4+/-22.6, both P < 0.05], but the level of IL-10 did
      not change significantly (ng/L: 143.6+/-32.5 vs. 140.4+/-22.3, P > 0.05).
      CONCLUSIONS: miR-155 ASO has the effect of inhibiting LPS-induced inflammatory
      response and improving prognosis in ALI mice.

PMID- 30220275
TI  - [Effect of high-flow nasal cannula oxygen therapy on improving the atelectasis in
      adults after cardiac surgeries: a Meta-analysis].
AB  - OBJECTIVE: To systematically evaluate the effect of high-flow nasal cannula
      oxygen (HFNC) on improving the atelectasis and respiratory function in adults
      after cardiac surgeries. METHODS: All randomized controlled trials (RCTs) about
      HFNC therapy for adults after cardiac surgeries published from January 2000 to
      March 2018 were searched through CNKI, CBM, VIP, Wanfang, PubMed, Springer Link,
      Embase, Web of Science, Cochrane Library. The references from relevant articles
      were searched. The experimental group was treated with HFNC while the control
      group treated with conventional oxygen therapy (COT). The outcome measurements
      included radiological atelectasis score (RAS), endotracheal reintubation rate and
      the length of intensive care unit (ICU) stay. Two researchers were responsible
      for literature screening, data extraction and quality evaluation respectively.
      Meta-analysis was performed with RevMan 5.2 software. Funnel plot was used to
      analyze the publication bias. RESULTS: A total of 4 RCTs were enrolled and 643
      patients were included (325 in experimental group and 318 in control group). Meta
      analysis showed that the tracheal reintubation rate in experimental group was
      lower than that in control group [odds ratio (OR) = 0.26, 95% confidence interval
      (95%CI) = 0.09-0.74, P = 0.01], but there was no significant difference in RAS
      [mean difference (MD) = -0.15, 95%CI = -0.50-0.21, P = 0.41] and the length of
      ICU stay (MD = 0.09, 95%CI = -0.09-0.26, P = 0.33) between experimental group and
      control group. Sensitivity analysis was performed in two trials with low risk of
      bias, which demonstrated that there was no significant difference in RAS between
      the two groups (MD = 0.06, 95%CI = -0.26-0.37, P = 0.73). It was shown by the
      funnel analysis that there was bias in the study of the length of ICU stay in the
      literature, while the bias of RAS and tracheal reintubation rate was low.
      CONCLUSIONS: Compared with COT, HFNC could reduce the rate of tracheal
      reintubation in adults after cardiac surgeries, but no difference was found in
      improving atelectasis or reducing the length of ICU stay.

PMID- 30220276
TI  - [Therapeutic effects of different doses of methylprednisolone on smoke inhalation
      induced acute lung injury in rats].
AB  - OBJECTIVE: To investigate the therapeutic effect of different doses of
      methylprednisolone (MP) in smoke inhalation-induced acute lung injury (SI-ALI).
      METHODS: Adult male Sprague-Dawley (SD) rats were divided into control group
      (group A, n = 6), smoke inhalation group (group B, smoke inhalation 30 minutes, n
      = 30) and smoke + MP 40, 4, 0.4 mg/kg intervention group (groups C, D, E;
      intraperitoneal injection of MP at 1 hour before smoke inhalation, n = 30)
      according to random number table method. The survival status of rats in each
      group was observed at 24 hours, and murine smoke inhalation induced trauma score
      (MSITS) according to the symptoms and signs of rats at 3 hours after smoke
      inhalation were scored. The blood of abdominal aorta of rats was collected. Then
      the rats were sacrificed to harvest bronchoalveolar lavage fluid (BALF) and lung
      tissue. The levels of interleukin (IL-6, IL-17a) in plasma and BALF were detected
      by enzyme linked immunosorbent assay (ELISA); the total number of white blood
      cells and the proportion of leukocytes or macrophages in BALF were calculated;
      the histopathological changes of lung were observed and the lung injury score was
      given; the expression of myeloperoxidase (MPO) and high mobility group protein B1
      (HMGB1) in lung tissue were detected by Western Blot. RESULTS: The 24-hour
      survival rate of group B rats was 33.67%. The survival rate of groups C, D and E
      (65.73%, 85.17%, 60.07%) were significantly higher than that of group B (all P <
      0.05), and the survival rate of group D was significantly higher than that of
      groups C and E. Diffuse inflammatory cell infiltration, intra-alveolar hemorrhage
      and a large amount of edema fluid were seen in the lung tissue of group B; and
      the lung injury score was significantly higher than that of group A. Compared
      with group B, the lung injury in different doses of MP group were decreased to
      different degrees, while the lung injury scores in groups C and D were
      significantly decreased (3.31+/-1.37, 2.62+/-0.98 vs. 5.52+/-0.97, both P <
      0.01); correlation analysis showed that MSITS score was significantly and
      positively correlated with lung injury score (r = 0.862, P < 0.001). The levels
      of plasma inflammatory factors and BALF protein, inflammatory cells and
      inflammatory factors, and the expression of MPO, HMGB1 in group B were
      significantly higher than those in group A. Compared with group B, the levels of
      inflammatory factors in plasma, and protein content, inflammatory cells and
      inflammatory factors in BALF in different doses of MP group were decreased to
      different degrees, with significant differences in groups C and D [plasma: IL-17a
      (pg/L): 49.28+/-27.12, 36.57+/-16.52 vs. 191.79+/-88.21; IL-6 (ng/L): 206.47+/
      109.96, 197.52+/-113.86 vs. 669.00+/-299.60; BALF: protein content (mg/L):
      892.0+/-164.5, 566.1+/-120.9 vs. 1 838.0+/-145.8; white blood cell count
      (*109/L): 5.40+/-1.67, 2.81+/-1.20 vs. 9.02+/-2.06; neutrophil ratio: 0.315+/
      0.081, 0.273+/-0.080 vs. 0.590+/-0.096; IL-17a (ng/L): 22.63+/-8.62, 18.92+/-8.43
      vs. 43.31+/-19.17; IL-6 (ng/L): 156.49+/-46.94, 123.66+/-64.91 vs. 253.43+/
      80.03; all P < 0.01]; in addition, the expression of MPO and HMGB1 protein in
      lung tissues of MP groups with different doses were significantly decreased, the
      expression of MPO in group D was significantly lower than that in group E
      [MPO/beta-actin (fold increase from group A): 2.14+/-0.97 vs. 4.35+/-0.87, P <
      0.01], the expression of HMGB1 in groups C and D were significantly lower than
      that in group E [HMGB1/beta-actin (fold increase from group A): 1.77+/-0.73,
      1.23+/-0.67 vs. 3.65+/-1.08, both P < 0.05]. CONCLUSIONS: MP can significantly
      improve the survival rate of SI-ALI rats and reduce the acute pulmonary and
      systemic inflammatory response. The MP effect of 4 mg/kg was better than 40 mg/kg
      and 0.4 mg/kg.

PMID- 30220277
TI  - [Influence of air pollution on the development of intensive care unit pneumonia
      patients: a summary of 2 454 cases from 2014 to 2016 in Nanchang City].
AB  - OBJECTIVE: To analyze the main characteristics of air pollution in Nanchang City,
      and discuss the correlation between air pollution exposure (especially PM2.5) and
      the development of pneumonia related intensive care unit (ICU) patients and their
      lag effect. METHODS: 2 454 patients who lived in Nanchang City admitted to ICU of
      Jiangxi Provincial People's Hospital from January 1st, 2014 to December 31st,
      2016 were enrolled. According to the diagnosis, the patients were divided into
      pneumonia group (156 cases) and non-pneumonia group (2 298 cases). The general
      clinical characteristics of patients and air pollution concentration in Nanchang
      in the year between 2014-2016 were collected. Multiple regression model was used
      to analyze the influence of meteorological factors on the condition of ICU
      patients associated with pneumonia. Using odds ratio (OR), the correlation
      intensity of air pollution exposure and pneumonia related ICU patients'
      development was reflected, and the confidence level of association intensity was
      reflected by the 95% confidence interval (95%CI). The distribution lag nonlinear
      model (DLNM) was established to evaluate the effect of air mass parameters on the
      time lag effect. RESULTS: The results of air pollution analysis in Nanchang City
      in the year between 2014-2016 showed that the annual average concentration of
      carbon monoxide (CO), sulfur dioxide (SO2) and nitrogen dioxide (NO2) was low and
      maintained at the same level in the year between 2014-2016. The annual average
      concentration of CO and NO2 increased in the year between 2014-2016, but the
      average annual concentration of SO2 decreased rapidly in the year between 2014
      2016, and the average annual concentration of PM2.5 tended to slow down after the
      year between 2014-2016. The annual average concentration of PM10 decreased in the
      year between 2014-2016, but continued to rise in the year between 2014-2016. The
      annual mean concentration of O3 showed a trend of continuous increase from the
      year between 2014-2016. The age of pneumonia group was generally higher than that
      of non-pneumonia group, most of them were male, and had higher expected mortality
      and acute physiology and chronic health evaluation II (APACHE II) score. The
      average air temperature in the pneumonia group was lower than that in the non
      pneumonia group on the day of entering the group, and the air pollutants such as
      PM2.5 and PM10 were significantly higher than those in the non-pneumonia group.
      The analysis of multiple regression models showed that PM2.5 and air temperature
      were significantly related to patients with ICU pneumonia on the day of entry
      (PM2.5: OR = 1.02, 95%CI = 1.00-1.03, P < 0.05; air temperature: OR = 0.96, 95%CI
      = 0.92-0.98, P < 0.05), and the effect of PM2.5 on patients with ICU pneumonia
      could last for at least 5 days (OR = 1.04, 95%CI = 1.00-1.09, P < 0.05), and the
      effect disappeared until the 7th day. According to the analysis of the influence
      of different concentrations of PM2.5 on ICU pneumonia patients, when the PM2.5
      concentration reached 200 MUg/m3, its effect on ICU pneumonia patients would last
      for 5 days (OR = 1.45, 95%CI = 1.07-1.76, P < 0.01). CONCLUSIONS: PM2.5 and air
      temperature are significantly related to the condition of ICU patients with
      pneumonia, and the influence of high concentration of PM2.5 on ICU patients with
      pneumonia has a lag effect.

PMID- 30220278
TI  - [Anti-inflammatory effects of penehyclidine hydrochloride on acute respiratory
      distress syndrome in rats].
AB  - OBJECTIVE: To investigate the anti-inflammatory effect of penehyclidine
      hydrochloride on oleic acid-induced acute respiratory distress syndrome (ARDS) in
      rats. METHODS: According to randomize number table method, 30 adult male Sprague
      Dawley (SD) rats were divided into control group, model group and treatment
      group. Catheters were placed in femoral vein in each group. The control group was
      injected with 1.1 mL/kg physiological saline; the model group was injected with
      0.1 mL/kg oleic acid and then injected with 1.0 mL/kg normal saline to establish
      ARDS model; the treatment group was injected with 0.1 mL/kg oleic acid and then
      injected with 1.0 mL/kg penehyclidine hydrochloride. At 3 hours after the model
      was established, blood gas analysis was carried out in each group, oxygenation
      index (PaO2/FiO2) was calculated, and the levels of serum interleukins (IL-1, IL
      6) were measured by enzyme linked immunosorbent assay (ELISA). Rats were
      sacrificed to harvest lung tissue, and the lung wet/dry ratio (W/D) was
      calculated; the morphological changes of lung tissue was observed under
      microscope; the superoxide dismutase (SOD) activity and malondialdehyde (MDA)
      levels were detected by colorimetry; the expression of tumor necrosis factor 
      alpha (TNF-alpha) in lung tissue was detected by immunohistochemical method. The
      correlations between lung W/D ratio and various indicators were analyzed using
      Pearson correlation test. RESULTS: Compared with the control group, PaO2/FiO2 in
      model group was significantly decreased, lung W/D ratio was significantly
      increased, serum IL-1, IL-6 levels and lung tissue MDA content were significantly
      increased, lung tissue SOD activity was significantly decreased; the alveolar
      space was filled with exudate, neutrophils and red blood cells, and there were
      obvious edema and broadening in pulmonary interstitial and alveolar under light
      microscope; the type II alveolar epithelial cells were partly destroyed,
      accompanied by lamellar body degeneration and emptying phenomenon under electron
      microscope; and immunohistochemistry showed that the positive expression of TNF
      alpha in lung tissue was significantly increased. Compared with the model group,
      PaO2/FiO2 in the treatment group was significantly improved [mmHg (1 mmHg = 0.133
      kPa): 204.42+/-31.61 vs. 113.91+/-47.78, P < 0.05], the lung W/D ratio was
      significantly decreased (5.80+/-0.44 vs. 6.82+/-0.59, P < 0.01), serum IL-1, IL-6
      levels and lung tissue MDA content were significantly decreased [IL-1 (MUg/L):
      18.38+/-0.28 vs. 20.04+/-0.39, IL-6 (MUg/L): 12.64+/-0.67 vs. 14.28+/-1.33, MDA
      (nmol/mg): 3.95+/-0.28 vs. 5.17+/-0.29, all P < 0.05], the activity of SOD in
      lung tissue was significantly increased (U/mg: 48.75+/-2.41 vs. 45.09+/-1.69, P <
      0.01), histological and pathological changes were significantly reduced, and the
      positive expression of TNF-alpha in lung tissue was significantly reduced
      [positive cell rate: (25.80+/-3.44)% vs. (38.82+/-3.59)%, P < 0.01]. CONCLUSIONS:
      Penehyclidine hydrochloride can effectively improve the oxygenation, alleviate
      lung injury and reduce pulmonary edema in oleic acid induced ARDS rat by
      decreasing lung W/D ratio, inhibiting oxidative stress and inflammatory response.

PMID- 30220279
TI  - [Effect of enteral nutrition time on pH value of gastric juice and ventilator
      associated pneumonia in critically ill patient].
AB  - OBJECTIVE: To investigate the effect of enteral nutrition (EN) start time on pH
      value of gastric juice and ventilator-associated pneumonia (VAP) in critically
      ill patients with invasive mechanical ventilation, so as to provide reference for
      the rational selection of EN timing. METHODS: Patients with mechanical
      ventilation who underwent EN treatment admitted to the intensive care unit (ICU)
      of the First Affiliated Hospital of Zhengzhou University from January 1st, 2016
      to November 30th, 2017 were enrolled, and the inclusion criteria were age >= 18
      years, acute physiology and chronic health evaluation II (APACHE II) <= 15, and
      nutritional risk screening (NRS 2002) >= 3. Patients were divided into two groups
      according to the start time of EN: early EN group (implementation of EN within 48
      hours after mechanical ventilation) and late EN group (implementation of EN after
      48 hours after mechanical ventilation). The pH value of gastric juice, VAP
      incidence, mechanical ventilation time, and the length of ICU stay were compared
      between the two groups. RESULTS: A total of 108 patients were included, 54 in the
      early EN group and 54 in the late EN group respectively. The pH value of gastric
      juice in early EN group was lower than that in late EN group [4.8 (3.8, 5.8) vs.
      5.6 (4.6, 6.6), P < 0.01]. There were 8 patients with VAP in the early EN group,
      3 of whom were early onset VAP. There were 17 patients with VAP in the late EN
      group, 10 of whom were early onset VAP. The incidence of VAP and the incidence of
      premature VAP in the early EN group were significantly lower than those in the
      late EN group (14.8% vs. 31.5%, 5.6% vs. 18.5%, both P < 0.05). The mechanical
      ventilation time [days: 7.5 (5.7, 9.0) vs. 8.6 (6.8, 10.7) and the length of ICU
      stay [days: 10.0 (8.5, 11.7) vs. 11.0 (9.5, 12.6)] in the early EN group were
      significantly shorter than those in the late EN group (all P < 0.05).
      CONCLUSIONS: At the same time of protecting gastric mucosa, early EN is helpful
      to reduce the incidence of VAP, reduce the duration of mechanical ventilation and
      the length of ICU stay, and improve the prognosis.

PMID- 30220280
TI  - [Effects of insulin caliper for blood glucose control on glucose control in
      emergent and critical patients].
AB  - OBJECTIVE: To observe the effects of insulin caliper for blood glucose control on
      glycemic central tendency, fluctuation and incidence of hypoglycemia, etc., in
      emergent and critical patients to evaluate its application value. METHODS: A
      prospective single-blinded randomized parallel controlled intervention study was
      conducted. One hundred patients with severe hyperglycemia requiring treatment
      with insulin infusion admitted to emergency department and intensive care unit
      (ICU) of the First Hospital of Jiaxing from November 2015 to November 2017 were
      enrolled, and they were divided into the caliper group (used patented product
      insulin calipers for blood glucose control to adjust insulin dose for blood
      glucose control) and the conventional group (used paper-based insulin dose
      modification scheme to adjust insulin dose for blood glucose control) on average
      by random number table, 50 in each group. The gender, age, acute physiology and
      chronic health evaluation II (APACHE II), sequential organ failure assessment
      (SOFA), the principal diseases, main factors affecting blood glucose (hepatic and
      renal insufficiency, hypoglycemic drugs, glucocorticoids, mechanical ventilation,
      enteral nutrition, parenteral nutrition, intravenous glucose use, etc.), blood
      glucose levels at each time node (once every 2 hours after insulin use and once
      every 4 hours after 16-72 hours), glycemic coefficient of variance (CV), glycemic
      lability index (GLUGLI) and mean amplitude of glycemic excursion (GLUMAGE),
      insulin dose, incidence of hypoglycemia, proportion of achieving the glucose
      control target at each time point, the length of ICU stay and hospitalization
      cost per patient were recorded and compared between the two groups. RESULTS:
      After excluding those with incomplete data and withdraw in the midway, 92
      patients were enrolled in the analysis finally, 47 in caliper group and 45 in
      conventional group. There were no significant differences in the incidence of the
      gender, age, APACHE II, SOFA, presence of infection at admission, previous
      diabetes history, glycosylated hemoglobin level, blood glucose at admission,
      proportion of patients after surgery, major diseases at admission and major
      factors affecting blood glucose between the two groups. A total of 1 379 blood
      glucose measurements were obtained in the caliper group and 1 332 blood glucose
      measurements were obtained in the conventional group. The glycemic measurements
      in caliper group were significantly lower than that in conventional group at each
      time point from 6-72 hours. Compared with conventional group, GLUGLI and GLUMAGE
      were significantly decreased in the caliper group [GLUGLI: 12.96 (8.73, 19.58)
      vs. 23.27 (13.07, 44.61), GLUMAGE (mmol/L): 0.66+/-0.22 vs. 0.87+/-0.28, both P <
      0.01]; there was a tendency towards decreasing incidence of hypoglycemia in the
      caliper group [8.51% (4/47) vs. 15.56% (7/45)], but no statistical difference was
      found (P > 0.05); the proportion of achieving the glucose control target was
      significantly increased in the caliper group [41.99% (579/1 379) vs. 27.18%
      (362/1 332), P < 0.01]. There were no significant differences in glycemic CV,
      insulin dose, proportion of hypoglycemic measurements in total measurements, and
      the length of ICU stay, the length of hospital stay, incidence of nosocomial
      infection, patient prognosis and cost between the two groups. CONCLUSIONS: For
      emergent and critical patients, insulin caliper for blood glucose control
      presents favorable application value for achieving glucose control target,
      reducing glycemic fluctuation, and lowering the incidence of hypoglycemia.
      Clinical trial registration: China clinical trial registration center,
      ChiCTR1800015024.

PMID- 30220282
TI  - [Effect of hemoperfusion combined with continuous veno-venous hemofiltration on
      acute paraquat poisoning: a Meta-analysis].
AB  - OBJECTIVE: To comprehensively evaluate the clinical efficacy of hemoperfusion
      (HP) combined with continuous veno-venous hemofiltration (CVVH) on acute paraquat
      poisoning (APP). METHODS: Literatures of Chinese and English randomized
      controlled trials (RCTs), case control and cohort study on HP combined with CVVH
      in the treatment of APP from the PubMed, Embase, Wanfang, and CNKI up to November
      2017 were enrolled (the subjects were > 16 years old). The obtained literatures
      were strictly screened and evaluated in quality, and data such as mortality, the
      life time of dead patients, inefficiency rate, incidence of multiple organ
      dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) were
      extracted. Meta-analysis was performed by RevMan 5.3. RESULTS: Twenty-one studies
      were included with 2 222 subjects, among whom 976 subjects were in HP combined
      with CVVH group (experimental group) and 1 246 subjects in HP group (control
      group). Compared with control group, the mortality in experimental group were
      significantly decreased [43.77% (362/827) vs. 55.26% (604/1 093), odds ratio (OR)
      = 0.68, 95% confidential interval (95%CI) = 0.56-0.82, P = 0.000 1], the life
      time of death patients was significantly prolonged [mean difference (MD) = 4.63,
      95%CI = 2.60-6.66, P < 0.000 01], incidence of MODS [25.93% (70/270) vs. 55.36%
      (155/280), OR = 0.26, 95%CI = 0.14-0.49, P < 0.000 1], and incidence of ARDS
      [30.37% (82/270) vs. 51.07% (143/280), OR = 0.42, 95%CI = 0.30-0.61, P < 0.000
      01], and inefficiency rate [8.72% (13/149) vs. 34.64% (53/153), OR = 0.17, 95%CI
      = 0.09-0.34, P < 0.000 01] were significantly reduced. Funnel chart showed that
      except the publication bias of mortality rate, there were less publication bias
      about other indicators among studies. CONCLUSIONS: HP combined with CVVH can
      significantly reduce the mortality of patients with APP compared with HP alone on
      the whole, prolong the life time and reduce the occurrence of MODS and ARDS, thus
      improving the treatment efficiency.

PMID- 30220281
TI  - [Safety and efficacy of regional citrate anticoagulation in continuous renal
      replacement therapy in the presence of acute kidney injury after hepatectomy].
AB  - OBJECTIVE: To evaluate the clinical effect and safety of regional citrate
      anticoagulation (RCA) in continuous renal replacement therapy (CRRT) for acute
      kidney injury (AKI) after hepatectomy. METHODS: A retrospective analysis of the
      clinical data of all patients with AKI after hepatectomy for CRRT admitted to
      surgical intensive care unit (ICU) of the First Affiliated Hospital of Xi'an
      Jiaotong University from January 19th, 2013 to January 19th, 2018 was performed.
      According to the different anticoagulants, the patients were divided into no
      anticoagulant group (NA group), low molecular heparin anticoagulation (LMHA)
      group and RCA group. The general data of patients during the perioperative
      period; renal function, the internal environment, electrolyte and blood
      coagulation function before and after CRRT; the filter time, the number of
      filters and adverse events (bleeding, frequent filter blood coagulation,
      metabolic alkalosis, metabolic acidosis, hypocalcemia, citrate accumulation,
      etc.) during CRRT were collected. Kaplan-Meier survival curve was used to analyze
      the life span of the first filter during different anticoagulation. RESULTS: A
      total of 67 cases were included in this study, including 11 in the NA group, 25
      in the LMHA group and 31 in the RCA group. There was no significant difference in
      gender, age, underlying disease, etiology (tumor), Child-Pugh stage (A or B), CT
      angiography (CTA), basic renal function [serum creatinine (SCr), cystatin C (Cys
      C)], the American Society of Anesthesiologists (ASA) stage; surgical approach;
      intraoperative bleeding volume, blood transfusion, blood pressure, time of
      duration of low blood pressure; and postoperative circulatory failure, hepatic
      insufficiency and sepsis among three groups. However, the length of ICU stay in
      RCA group was significantly less than the LMHA group and NA group (days: 8.16+/
      2.24 vs. 10.48+/-5.11, 13.29+/-6.64, both P < 0.05). Compared with before CRRT,
      the levels of SCr, Cys C and Lac were significantly decreased in RCA group and
      LMHA group after CRRT [SCr (MUmol/L): 89.02+/-21.90 vs. 248.30+/-55.32, 105.10+/
      49.00 vs. 270.10+/-156.00; Cys C (mg/L): 2.18+/-0.95 vs. 2.94+/-1.26, 2.26+/-0.76
      vs. 3.07+/-0.90; Lac (mmol/L): 2.21+/-1.46 vs. 3.62+/-1.73, 2.37+/-1.24 vs.
      4.03+/-1.69, all P < 0.05]; in addition, LMHA group and NA group had significant
      effects on hemoglobin (Hb), platelet count (PLT) and activated partial
      thromboplastin time (APTT) after CRRT [Hb (g/L): 85.4+/-5.1 vs. 99.6+/-23.6,
      80.0+/-7.6 vs. 101.4+/-7.8; PLT (*109/L): 27.60+/-8.22 vs. 62.04+/-16.49, 21.36+/
      3.91 vs. 61.45+/-17.69; APTT (s): 63.07+/-10.25 vs. 41.52+/-3.65, 49.56+/-5.77
      vs. 41.09+/-3.45, all P < 0.05]; at the same time, Cys C level and prothrombin
      time (PT) in the NA group after CRRT treatment were significantly increased
      compared with the others [Cys C (mg/L): 3.59+/-0.64 vs. 2.29+/-0.51, PT (s):
      26.41+/-2.43 vs. 23.64+/-1.92 , both P < 0.05]. Finally, the time of filters
      (hours: 60.52+/-8.82, 31.04+/-7.03, 13.73+/-6.26, F = 183.412, P < 0.001) and the
      number of filter during treatment (number: 2.03+/-0.60, 3.12+/-0.73, 4.64+/-1.29,
      F = 45.933, P < 0.001) in the RCA group, LMHA group and NA group had
      statistically significant difference. Meanwhile, the incidence of adverse events
      such as bleeding (0 vs. 4, 7, chi 2 = 23.961, P < 0.001) and frequent filter
      coagulation (1 vs. 10, 11, chi 2 = 35.413, P < 0.001) in RCA group was
      significantly lower than that in LMHA group and NA group. Kaplan-Meier survival
      analysis showed that the life time of the first filter in RCA group was
      significantly longer than that in LMHA group and NA group (chi2 = 139.45, P <
      0.05). CONCLUSIONS: The application of RCA in patients with AKI after hepatectomy
      during CRRT is safe and effective, which can significantly prolong the life of
      the filter and reduce the risk of bleeding.

PMID- 30220283
TI  - [Clinical features and prognosis analysis of the elderly and youth patients with
      acute severe poisoning].
AB  - OBJECTIVE: To investigate the clinical features and prognosis risk factors of the
      elderly and youth patients with acute severe poisoning. METHODS: Adult patients
      with acute severe poisoning in the emergency intensive care unit (EICU) of
      Nanjing Drum Tower Hospital from January 2008 to December 2017 were enrolled. The
      patients were divided into the elderly group (age >= 60 years) and the youth
      group (16 years <= age < 60 years), the clinical data of the two groups were
      analyzed. The patients were divided into survival group and death group according
      to the prognosis of 28-day, binary multivariate Logistic regression was used to
      analyze the risk factors of mortality of the elderly and youth patients; receiver
      operating characteristic curve (ROC) was used to assess the predictive value of
      acute physiology and chronic health evaluation II (APACHE II) in mortality of
      youth patients. RESULTS: A total of 343 patients with acute severe poisoning were
      included, 89 in the elderly group and 254 in the youth group. (1) Clinical
      features: compared with the youth group, the elderly group had higher proportion
      of basic diseases included hypertension, type 2 diabetes and coronary heart
      disease, higher the initial APACHE II scores at admission, higher the proportion
      of invasive mechanical ventilation and respiratory failure, and longer the length
      of EICU stay and the length of hospital stay. The main poisoning causes of
      elderly and youth patients were suicide (58.43%, 83.86%) and accidents (38.20%,
      13.39%). The most common poisoning types of elderly patients were sedative
      hypnotics (23.60%) and organophosphorus pesticides (22.47%); the youth patients
      were mainly paraquat (42.52%) and organophosphorus pesticide (17.32%). There were
      28 patients died (31.46%) in the elderly group and the cause of death were
      respiratory failure (53.57%), circulatory failure (32.14%) and multiple organ
      dysfunction syndrome (MODS, 14.29%). There were 67 patients died (26.38%) in the
      youth group and the cause of death were respiratory failure (59.70%), MODS
      (20.90%) and circulatory failure (19.40%). (2) Risk factors of deaths: the APACHE
      II score, incidence of acute kidney injury (AKI) and MODS in the elderly death
      group were significantly higher than those in the elderly survival group.
      Logistic regression analysis showed that AKI was the independent risk factor for
      death in elderly patients [odds ratio (OR) = 8.449, 95% confidence interval
      (95%CI) = 2.347-30.410, P = 0.001]. The proportion of female, APACHE II score,
      and the incidence of AKI, respiratory failure and MODS in the youth death group
      were significantly higher than those in the youth survival group. Logistic
      regression analysis showed that APACHE II score (OR = 1.175, 95%CI = 1.081-1.277,
      P = 0.001), AKI (OR = 34.470, 95%CI = 11.681-101.722, P = 0.001) and MODS (OR =
      3.834, 95%CI = 1.264-11.636, P = 0.018) were the independent factors for death in
      the youth patients. (3) Predictive value: the initial APACHE II score was useful
      for predicting prognosis of youth patients with acute severe poisoning. The
      APACHE II score to predict the death of the area under the ROC curve (AUC) was
      0.744 (95%CI = 0.681-0.806, P = 0.001); the cut-off was 5, the sensitivity was
      92.54%, the specificity was 51.34%, the positive predictive value was 65.53%, the
      negative predictive value was 87.31%, the positive likelihood ratio was 1.902,
      and the negative likelihood ratio was 0.145. CONCLUSIONS: Patients with acute
      severe poisoning have their own clinical characteristics. To reduce the morbidity
      and improve the prognosis, we should strengthen the pre-hospital management and
      optimize the clinical treatment process.

PMID- 30220284
TI  - [Protective effects of high-density lipoprotein on mice cardiomyocytes induced by
      oxygen and glucose deprivation through Akt signaling pathway].
AB  - OBJECTIVE: To investigate the protective effect of high-density lipoprotein (HDL)
      on the mice cardiac myocytes induced by oxygen and glucose deprivation (OGD).
      METHODS: Cardiac cells of primary scavenger receptor-B1 knockout mice (SR-B1-/-)
      and normal C57 mice (SR-B1+/+) were obtained by protease digestion and
      differential adhesion method. (1) The two kinds of cells were divided into normal
      control group (Con group), OGD group, OGD+HDL group. Propidium iodide (PI)
      staining were used to determine the necrosis of cardiac myocytes. (2) SR-B1+/+
      cardiac cells were divided into Con group, OGD group, OGD+HDL group, and
      phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) inhibitor LY294002
      group. PI staining were used to determine the necrosis of cardiac myocytes. TUNEL
      staining was used to determine the cell apoptosis. The kit was used to determine
      the contents of MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase
      (LDH) in the culture medium supernatant. The expressions of SR-B1 and Akt protein
      were determined by Western Blot. RESULTS: (1) In SR-B1+/+ cardiomyocytes, HDL
      could inhibit cell necrosis induced by OGD. There was no protective effect of HDL
      on OGD in the SR-B1-/- cardiomyocytes. (2) The study of SR-B1+/+ cells was showed
      that compared with Con group, necrotic cells were significantly increased and
      cell activity were significantly decreased, the cell viability were significantly
      decreased, the contents of LDH and CK-MB in supernatant were significantly
      increased, the expressions of phosphorylated Akt (p-Akt) and SR-B1 were
      significantly decreased in OGD group. Compared with OGD group, the number of
      necrotic cells in the OGD+HDL group was significantly decreased [PI positive
      cells rate: (26.71+/-5.94)% vs. (64.24+/-18.34)%], the cell activity was
      significantly increased [(63.84+/-6.95)% vs. (26.71+/-5.13)%], the contents of
      LDH and CK-MB in supernatant were significantly decreased [LDH (U/L): 896.3+/
      161.5 vs. 1 568.3+/-243.5, CK-MB (U/L): 304.3+/-72.9 vs. 583.6+/-81.6], the
      expressions of p-Akt and SR-B1 were significantly increased (p-Akt/t-Akt: 0.84+/
      0.13 vs. 0.18+/-0.06, SR-B1/beta-actin: 1.23+/-0.19 vs. 0.09+/-0.02), with
      statistically significant differences (all P < 0.05). Compared with OGD+HDL
      group, necrotic cells in LY294002 group were increased, cell activity was
      decreased, LDH and CK-MB contents in supernatant were increased, p-Akt and SR-B1
      expressions were decreased; there was no statistical difference between LY294002
      group and OGD group. There was no significant difference in cell apoptosis among
      the 4 groups. CONCLUSIONS: HDL has protective effect on the mice myocardial
      cells. The mechanism may be related with the up regulation of the expression of
      SR-B1 protein by the activation of PI3K/Akt pathway.

PMID- 30220285
TI  - [Comparison of the structures of the medical staff and the operation situations
      of the departments of critical care medicine between the provincial and county
      level hospitals of Guizhou Province in 2017].
AB  - OBJECTIVE: To understand the situations of departments of intensive care units
      (ICUs) of different level hospitals in Guizhou Province, and to provide
      directions and evidences for improving quality control in critical care medicine.
      METHODS: A county-level hospital and a provincial-level hospital's comprehensive
      ICU in Guizhou Province were selected to record and analyze and compare the
      structural indicators, patient admission and transfer, disease distribution,
      ventilator associated pneumonia (VAP), intravascular catheter related blood
      stream infection (CRBSI) and catheter-associated urinary tract infection (CAUTI)
      of the two hospitals' comprehensive ICU in 2017. RESULTS: The ICU of the People's
      Hospital of Suiyang County (county hospital) was found in 2012, and the ICU of
      the Affiliated Hospital of Guizhou Medical University (provincial hospital) was
      found in 1994. Until 2017, there were 10 and 46 beds, 6 (all of them hold
      bachelor's degree) and 18 physicians (6 of them hold PhD, 5 of them hold master's
      degree, 7 of them hold bachelor's degree), 17 (4 of them hold bachelor's degree,
      13 of them hold college degree or graduated from secondary school) and 69 nurses
      (2 of them hold master's degree, 53 of them hold bachelor's degree, 14 of them
      hold college degree or graduated from secondary school) in the two ICUs
      respectively, there were significant differences in the education background of
      the physicians and nurses between the two ICUs (both P < 0.01). During 2017, 471
      cases were admitted to the ICU of the county hospital while 1 633 cases were
      admitted to the ICU of the provincial hospital. Compared with the ICU of the
      provincial hospital, the ratio of the patients with acute physiology and chronic
      health evaluation II (APACHE II) >= 15 at admission was lower (74.8% vs. 85.1%, P
      < 0.01), the ratio of direct admission was higher (30.8% vs. 17.4%, P < 0.01),
      the ratio of the patients admitted to the ICU more than once was lower (0.8% vs.
      5.0%, P < 0.01), the ratio of the patients whose the length of ICU stay less than
      24 hours was higher (51.6% vs. 13.7%, P < 0.01), the ratio of the patients whose
      the length of ICU stay more than 28 days was lower (1.1% vs. 2.9%, P < 0.05), the
      ratio of the patients discharged against-advice (25.5% vs. 20.5%, P < 0.05) was
      higher, the ratio of the patients transferred to other hospitals was higher (5.1%
      vs. 0.3%, P < 0.05), and the ICU mortality was lower (4.0% vs. 13.9%, P < 0.01)
      in the ICU of the county hospital. The top three kinds of diseases treated in the
      ICU of the county hospital were brain injury (27.4%), trauma (19.1%) and
      toxication (6.8%); while in the ICU of the provincial hospital were brain injury
      (18.6%), sepsis (16.2%) and severe acute pancreatitis (4.8%). In addition, the
      incidences of VAP, CRBSI and CAUTI in the ICU of the county hospital were 10.0/1
      000 ventilator days, 1.4/1 000 catheter days, 0.5/1 000 catheter days; while in
      the ICU of the provincial hospital were 5.8/1 000 ventilator days, 2.0/1 000
      catheter days, 3.7/1 000 catheter days, respectively. CONCLUSIONS: There are
      short of physicians and nurses in the ICU of the provincial and county hospitals
      in Guizhou Province, and the educational level of the medical staff in the ICU of
      the county hospital is relatively low. Moreover, there were significant
      differences in the admissions and treatments and the outcomes of the critically
      ill patients between the two ICUs. The characteristics of the ICUs of county
      hospitals should be fully considered when the quality control of critical care
      medicine and continuing medical education are done.

PMID- 30220286
TI  - [Effect of iron metabolism of preoperation on the length of intensive care unit
      stay in liver transplant recipients].
AB  - OBJECTIVE: To evaluate the effect of iron metabolism of preoperation on the
      length of intensive care unit (ICU) stay in liver transplant recipients. METHODS:
      A retrospective study was conducted. 120 adult liver transplant recipients
      admitted to Tianjin First Central Hospital from September 2015 to September 2017
      were enrolled. The basic data, model of end-stage liver disease (MELD) evaluation
      system score at admission; iron metabolism index, routine blood test, blood
      biochemistry, coagulation time and C-reactive protein (CRP) level within 24 hours
      after admission; intraoperative clinical indicators such as operation time,
      operation bleeding volume, red blood cells and fresh frozen plasma input volume,
      hot ischemia time, cold ischemia time, urine volume; and the length of ICU stay
      were collected. All patients were divided into iron deficiency group (ID group;
      serum ferritin < 100 MUg/L, or serum ferritin 100-300 MUg/L and transferrin
      saturation < 0.20) and non-iron deficiency group (non-ID group; serum ferritin >
      300 MUg/L, or serum ferritin 100-300 MUg/L and transferrin saturation > 0.20)
      according iron deficiency standard. The indexes of iron metabolism, basic data
      and clinical indicators of two groups were compared. The correlation between
      serum ferritin level and the length of ICU stay was analyzed by Pearson
      correlation. RESULTS: Compared with non-ID group, the levels of serum iron
      concentration and serum ferritin were significantly decreased in ID group [serum
      iron concentration (MUmol/L): 3.50+/-1.62 vs. 14.50+/-2.31, serum ferritin
      (MUg/L): 67.00+/-31.54 vs. 315.00+/-36.73, both P < 0.01], infusion volume of
      intraoperative red blood cells and fresh frozen plasma were significantly
      increased, and the length of ICU stay was significantly prolonged (days: 6.5+/
      2.4 vs. 3.3+/-0.5, P < 0.01). There was no significant difference in transferrin
      saturation, CRP and other clinical indicators between the two groups. Correlation
      analysis showed that serum ferritin level was negative correlated with the length
      of ICU stay (r = -0.768, P < 0.001). CONCLUSIONS: Preoperative iron deficiency in
      liver transplant recipients will lead to increased blood transfusion and
      prolonged length of ICU stays.

PMID- 30220287
TI  - [Hemophagocytic lymphohistiocytosis: tortuous experience in the diagnosis and
      treatment of one lymphoma].
AB  - OBJECTIVE: The etiology of hemophagocytic lymphohistiocytosis (HLH) is
      complicated and difficult to diagnose, unexplained HLH often with hematological
      malignancies. Invasive biopsy can help to find etiology, the results may be
      affected by the technique and the location of the puncture site. Multiangle
      puncture can improve the success rate, but the corresponding risk increases. A
      patient with HLH was admitted to Affiliated Hospital of Zunyi Medical College.
      The etiology was unknown. Active symptomatic support treatment was conducted, at
      the same time, finding the evidence of viral infection, autoimmune disease
      related detection, blood culture, bone marrow puncture smear and spleen biopsy
      were performed respectively to find the pathogen basis. Spleen hemorrhage was not
      being controlled after spleen biopsy in patients, and emergency splenectomy was
      adopted to stop bleeding for saving lives. Finally, the patients died of low
      protein, pulmonary edema and respiratory failure. The bone marrow puncture and
      spleen biopsy failed to provide the basis for tumor invasion, while the spleen
      pathological slices plus immunohistochemical indicate diffuse large B cell
      lymphoma (DLBCL) after splenectomy, which was identified as malignant tumor
      associated hemophagocytic syndrome. Underscoring the high risk of bleeding after
      tumor-associated splenomegaly puncture and the importance of having emergency
      plans. Through analyzing the clinical characteristics, diagnosis and treatment of
      this patient, we hope to improve the clinicians' understanding of HLH and
      lymphoma.

PMID- 30220288
TI  - [Progress on nuclear factor-E2 related factor 2 transcription factors in sepsis].
AB  - OBJECTIVE: Sepsis is a critical complication of severe trauma, large area burns,
      infection, and major surgery etc., which can induce septic shock and multiple
      organ dysfunction syndrome (MODS), and its incidence and mortality are always
      high. Nuclear factor-E2 related factor 2 (Nrf2) is an important transcription
      factor of antioxidant stress response. It plays a key role in the treatment of
      sepsis by regulating the expression of antioxidant enzyme and phase II
      detoxification enzyme mediated by antioxidant response element (ARE). In this
      article we review the changes, related regulation mechanism and reversing
      measures of Nrf2 in sepsis, aiming to provide a reference for the effective
      intervention measures of sepsis.

PMID- 30220289
TI  - [Research progress on inflammation and right ventricular failure].
AB  - OBJECTIVE: Right ventricular failure (RVF) is the main cause of death in patients
      with cardiopulmonary disease, such as pulmonary arterial hypertension (PAH),
      pulmonary embolism, acute respiratory distress syndrome, and right ventricular
      infarction. The exact cellular and molecular mechanisms underlying RVF remains
      unclear. Inflammation may play an important role during the development of RVF,
      as it does in left heart failure. Cardiac inflammation has been shown in RVF
      patients and animal models, which played a role in the impairment of the right
      ventricular contraction and in the maladaptive remodeling. Inflammation plays a
      dual role in the development of cardiopulmonary disease and its anti-inflammatory
      therapies may have double benefits for RVF patients. This review summarizes the
      evidence of inflammation in RVF and research progresses of inflammation in the
      development of RVF to provide a reference for further exploring the mechanism of
      inflammation in RVF.

PMID- 30220290
TI  - Time-to-onset of cold and flu symptom relief: A randomized, double-blind, placebo
      controlled pilot study for a multi-symptom combination product.
AB  - OBJECTIVE: Evaluate effects of a multisymptom tablet on cold and flu symptoms
      within 4 hours post-administration. MATERIALS AND METHODS: This was a randomized,
      double-blind, placebo-controlled study in adults with cold and flu symptoms.
      Eligible participants with at least moderate common cold or flu symptoms and
      symptom onset <= 48 hours before screening were assigned to a single multiple
      active-ingredient tablet (containing paracetamol, pseudoephedrine hydrochloride,
      dextromethorphan hydrobromide, and chlorpheniramine maleate) or placebo tablet.
      Participants rated severity of each symptom (sore throat, headache, extremity
      pain, nasal congestion, sneezing, runny nose, and cough) from 0 (absent) to 3
      (severe) at 15 and 30 minutes and 1, 2, 3, and 4 hours post administration. The
      total symptom score (TSS) was calculated as the sum of the individual symptom
      scores (primary endpoint). Participants rated global response to treatment on a
      scale from 0 (ineffective) to 4 (excellent). Adverse events (AEs) were recorded
      throughout. RESULTS: Of 53 participants randomized, 52 received active tablet (n
      = 25) or placebo tablet (n = 27). Change from baseline in TSS throughout the 4
      hour post-administration period was similar between groups. An efficacy criterion
      of 30% decrease in TSS at assessment points was not met (range, -1.91 to 8.94%).
      There were also no significant differences between groups in mean symptom scores
      for individual symptoms or global response to treatment. Four non-serious
      treatment-emergent adverse events occurred. CONCLUSION: In this exploratory pilot
      study, a multisymptom cold and flu tablet was well tolerated but did not differ
      from placebo tablet with regard to onset of action following a single dose.?.

PMID- 30220291
TI  - Predictability of serum vancomycin concentrations using the kinetic estimated
      glomerular filtration rate formula for critically ill patients?.
AB  - OBJECTIVE: To evaluate the predictability of serum vancomycin concentrations of
      critically ill patients using the new kinetic estimated glomerular filtration
      rate (KeGFR) and other three established eGFR formulae. MATERIALS AND METHODS: We
      calculated serum vancomycin concentrations using software provided by the
      manufacturer of vancomycin. RESULTS: Data were collected from 122 hospitalized
      adults. The mean error and mean absolute error of KeGFR were 0.81 ug/mL and 4.46
      ug/mL, respectively. The root mean squared prediction error of KeGFR was the
      highest (6.67 ug/mL) among the four formulae. CONCLUSION: The predictability of
      KeGFR formula did not show good accuracy in critically ill patients.?.

PMID- 30220292
TI  - Changes in blood concentration of mycophenolic acid and FK506 in a heart
      transplant patient treated with plasmapheresis?.
AB  - OBJECTIVE: Prior to heart transplant, sensitization to human leukocyte antigen
      can occur after blood transfusions used during implantation of ventricular assist
      devices. The result is an increased risk of antibody-mediated rejection (AMR)
      after heart transplant. While plasmapheresis (PPH) treats serious AMR cases, what
      subsequent changes occur in the blood concentrations of immunosuppressive agents
      is still unknown. We investigated pre- and post-PPH changes in blood
      concentrations of tacrolimus (FK506) and mycophenolic acid (MPA) in a heart
      transplant patient experiencing AMR. CASE: A 40-year-old woman with a history of
      dilated cardiomyopathy had heart transplantation for advanced heart failure.
      Since the patient was donor-specific antibody-positive and at risk for AMR,
      intravenous immunoglobulin therapy and PPH were performed just before
      transplantation. Triple combination immunosuppressive therapy was initiated, but
      4 days after transplantation, panel-reactive antibody increased drastically, and
      AMR was diagnosed by biopsy. Multidisciplinary therapy, including PPH, was
      performed. Blood samples were collected to measure blood concentrations of FK506
      and MPA before and after passage through the plasma separator. RESULTS: The
      elimination efficiency of FK506 from PPH was -6.25 - 2.25%, while the elimination
      efficiency of MPA was much greater at 32.35 - 51.43%. CONCLUSION: These results
      show the necessity of carefully considering changes in blood concentrations that
      occur in immunosuppressive agents due to PPH, including the pharmacokinetics of
      the particular drug. However, proper timing of the PPH relative to drug
      administration can also minimize immunosuppressant loss.?.

PMID- 30220293
TI  - Evaluation of reference-scaled average bioequivalence of two oral formulations of
      abiraterone acetate in healthy Chinese subjects?.
AB  - OBJECTIVE: This study was designed to evaluate the pharmacokinetic (PK)
      properties and bioequivalence (BE) of two 250-mg tablet formulations of
      abiraterone acetate: a newly developed generic formulation (test) and a branded
      formulation (reference) in healthy adult Chinese subjects under fasted (n = 40)
      and fed (n = 40) conditions. MATERIALS AND METHODS: The comparison was performed
      using a single-dose, open, randomized, and four-way replicate study. The
      concentration of abiraterone in blood samples taken over 48 hours was determined
      by liquid chromatography tandem mass spectrometry (LC-MS/MS). To assess the BE of
      the test and reference formulations, confidence intervals (CI, 90%) for the peak
      plasma concentration (Cmax) and area under the concentration-time curves (AUC0-t
      and AUC0-infinity) were calculated using the reference-scaled average
      bioequivalence (RSABE) method. RESULTS: The results showed that the 90% CIs for
      the ratios of Cmax, AUC0-t, and AUC0-infinity in the fasted study were 90.14 -
      114.11, 93.96 - 115.07, and 93.72 - 113.331, respectively. For the fed study, the
      90% CIs were 81.83 - 102.51, 91.51 - 104.89, and 91.46 - 104.58, respectively.
      CONCLUSION: In conclusion, the tested 250-mg abiraterone tablets were
      bioequivalent to 250-mg Zytiga tablets (reference) under both fasted and fed
      conditions. In addition, food intake increased the systemic exposure and Cmax of
      abiraterone by 3-fold and 7-fold, respectively.?.

PMID- 30220294
TI  - Tea consumption and risk of breast cancer: A meta-analysis.

PMID- 30220295
TI  - Avocado as an emerging trigger for food protein-induced enterocolitis syndrome.

PMID- 30220296
TI  - Recurrent FPIES to wheat after multiple tolerant exposures in a male infant.

PMID- 30220297
TI  - Mold exposure affects the development of atopic dermatitis in infants with skin
      barrier dysfunction.

PMID- 30220298
TI  - Repairing the human esophagus with tissue engineering.

PMID- 30220299
TI  - Technical feasibility of endoscopic submucosal dissection for local failure after
      chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma.
AB  - BACKGROUND AND AIMS: Salvage endoscopic submucosal dissection (ESD) after
      chemoradiotherapy can be technically difficult as a result of radiation-induced
      fibrosis. We aimed to evaluate the technical feasibility of ESD for local failure
      after chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) and for
      other primary lesions within the irradiation field. METHODS: Consecutive patients
      treated with ESD for superficial ESCC between December 2009 and May 2017 were
      investigated retrospectively and stratified into group A (33 patients, 35
      lesions; local failure at the primary site after chemoradiotherapy), group B (25
      patients, 34 lesions; second primary lesions within the irradiation field), and
      group C (550 patients, 596 lesions; radiotherapy-naive superficial ESCC). We
      evaluated procedural success rate, en bloc resection rate, 1-year local relapse
      free survival (LRFS) rate, procedure time, and incidence of major adverse events.
      RESULTS: The rates of procedural success and en bloc resection, respectively,
      were significantly lower in group A (89%, 86%) than in groups B (100%, 100%) and
      C (100%, 98%). The 1-year LRFS rates were 86%, 100%, and 99% in groups A, B, and
      C, respectively, and significantly lower in group A than in group C. Serious
      adverse events including perforation were not observed in groups A and B;
      perforation occurred only in group C (2.8%). CONCLUSIONS: ESD is technically
      feasible in patients with local failure, especially as initial salvage treatment
      and as treatment for second primary lesions within the irradiation field.

PMID- 30220300
TI  - A prospective multicenter study using a new multiband mucosectomy device for
      endoscopic resection of early neoplasia in Barrett's esophagus.
AB  - BACKGROUND AND AIMS: Early neoplasia in Barrett's esophagus (BE) can be
      effectively and safely removed by endoscopic resection (ER) using multiband
      mucosectomy (MBM). This study aimed to document performance of a novel MBM device
      designed for improved visualization, easier passage of accessories, and better
      suction power compared with other marketed MBM devices. METHODS: This
      international, single-arm, prospective registry in 14 referral centers (Europe,
      10; United States, 3; Canada, 1) included patients with early BE neoplasia
      scheduled for ER. The primary endpoint was successful ER defined as complete
      resection of the delineated area in 1 procedure. Secondary outcomes were adverse
      events and procedure time. RESULTS: A total of 332 lesions was included in 291
      patients (248 men; mean age, 67 years [standard deviation, 9.6]). ER indication
      was high-grade dysplasia in 64%, early adenocarcinoma in 19%, lesion with low
      grade dysplasia in 11%, and a lesion without definite histology in 6%. Successful
      ER was reached in 322 of 332 lesions (97%; 95% confidence interval [CI], 94.6%
      98.4%). A perforation occurred in 3 of 332 procedures (.9%; 95% CI, .31%-2.62%),
      all were managed endoscopically, and patients were admitted with intravenous
      antibiotics during days 2, 3, and 9. Postprocedural bleeding requiring an
      intervention occurred in 5 of 332 resections (1.5%; 95% CI, .65%-3.48%).
      Dysphagia requiring dilatation occurred in 11 patients (3.8%; 95% CI, 2.1%-6.6%).
      Median procedure time was 16 minutes (interquartile range, 12.0-26.0).
      CONCLUSIONS: In expert hands, the novel MBM device proved to be effective for
      resection of early neoplastic lesions in BE, with successful ER in 97% of
      procedures. Severe adverse events were rare and were effectively managed
      endoscopically or conservatively. (Clinical trial registration number:
      NCT02482701.).

PMID- 30220302
TI  - Managing underperformance in endoscopy: a pragmatic approach.

PMID- 30220301
TI  - The association among diet, dietary fiber, and bowel preparation at colonoscopy.
AB  - BACKGROUND AND AIMS: Pre-colonoscopy dietary restrictions vary widely and lack
      evidence-based guidance. We investigated whether fiber and various other
      foods/macronutrients consumed during the 3 days before colonoscopy are associated
      with bowel preparation quality. METHODS: This was a prospective observational
      study among patients scheduled for outpatient colonoscopy. Patients received
      instructions including split-dose polyethylene glycol, avoidance of
      vegetables/beans 2 days before colonoscopy, and a clear liquid diet the day
      before colonoscopy. Two 24-hour dietary recall interviews and 1 patient-recorded
      food log measured dietary intake on the 3 days before colonoscopy. The Nutrition
      Data System for Research was used to estimate dietary exposures. Our primary
      outcome was the quality of bowel preparation measured by the Boston Bowel
      Preparation Scale (BBPS). RESULTS: We enrolled 201 patients from November 2015 to
      September 2016 with complete data for 168. The mean age was 59 years (standard
      deviation, 7 years), and 90% of colonoscopies were conducted for
      screening/surveillance. Only 17% and 77% of patients complied with diet
      restrictions 2 and 1 day(s) before colonoscopy, respectively. We found no
      association between foods consumed 2 and 3 days before colonoscopy and BBPS
      scores. However, BPPS was positively associated with intake of gelatin, and
      inversely associated with intake of red meat, poultry, and vegetables on the day
      before colonoscopy. CONCLUSIONS: Our findings support recent guidelines
      encouraging unrestricted diets >1 day before colonoscopy if using a split-dose
      bowel regimen. Furthermore, we found no evidence to restrict dietary fiber 1 day
      before colonoscopy. We also found evidence to promote consumption of gelatin and
      avoidance of red meat, poultry, and vegetables 1 day before colonoscopy.

PMID- 30220304
TI  - Clinical value of plasma renin activity and aldosterone concentration in the
      evaluation of secondary hypertension, a case of reninoma.

PMID- 30220303
TI  - Successful liver-directed gene delivery by ERCP-guided hydrodynamic injection
      (with videos).
AB  - BACKGROUND AND AIMS: A simple, safe, targeted, and efficient in vivo DNA delivery
      system is necessary for clinical-grade liver-targeted gene therapy in humans.
      Intravascular hydrodynamic gene delivery has been investigated in large animal
      models, but translation to humans has been hampered by its technical challenges,
      invasiveness, and potential for significant cardiovascular adverse events. We
      posited that intrabiliary delivery of DNA plasmids via ERCP-guided hydrodynamic
      injection could overcome these obstacles. METHODS: Twelve pigs (40-50 kg) were
      divided into 3 groups (4 per group) and survived 21, 30, or 60 days. ERCP was
      performed by inflating a balloon catheter in the common hepatic duct and creating
      a closed space between it and the liver parenchyma. Last, a solution composed of
      plasmid/sleeping beauty (SB) mix was injected under pressure through the catheter
      into the closed space. Swine were killed at the 3 different time points and liver
      tissue harvested. Plasmid DNA expression and functional translated protein
      expression were assessed. RESULTS: ERCP-guided hydrodynamic delivery of naked
      plasmid DNA facilitated by pCytomegalovirus-Sleep Beauty (pCMV-SB) transposons
      was technically feasible and devoid of cardiovascular and local adverse events in
      all 12 pigs. Furthermore, plasmid DNA (both single and combination) was
      successfully transferred into swine hepatocytes in all 12 pigs. Additionally,
      stable integration of the DNA constructs in hepatocyte genomic DNA was reliably
      noted at all 3 time points. In the 4 swine that were kept alive to 60 days,
      successful genomic integration and subsequent protein expression was observed in
      the targeted liver tissue. CONCLUSIONS: ERCP-guided hydrodynamic delivery of gene
      therapy may usher in the next chapter in gene therapy with the potential to
      impact a variety of single-gene, complex genetic, and epigenetic liver diseases.
      It also raises the possibility that other nucleic acid therapeutics (microRNA,
      lncRNA, siRNA, shRNA) could similarly be delivered.

PMID- 30220305
TI  - A proposed mechanism for the Berecek phenomenon with implications for
      cardiovascular reprogramming.
AB  - Berecek et al reported in the 1990s that when spontaneously hypertensive rat
      (SHR) mating pairs were treated with captopril and the resulting pups were
      continued on the drug for 2 months followed by drug discontinuation, the pups did
      not develop full blown hypertension, and the cardiovascular structural changes
      associated with hypertension in SHR were mitigated. The offspring of the pups
      also displayed diminished hypertension and structural changes, suggesting that
      the drug therapy produced a heritable amelioration of the SHR phenotype. This
      observation is reviewed. The link between cellular renin angiotensin systems and
      epigenetic histone modification is explored, and a mechanism responsible for the
      observation is proposed. In any case, the observations of Berecek are
      sufficiently intriguing and biologically important to merit re-exploration and
      definitive explanation. Equally important is determining the role of renin
      angiotensin systems in epigenetic modification.

PMID- 30220306
TI  - Electroacupuncture Ameliorates Cognitive Impairment and Spontaneous Low-Frequency
      Brain Activity in Rats with Ischemic Stroke.
AB  - BACKGROUND: To evaluate whether electroacupuncture (EA) at Baihui (DU20) and
      Shenting (DU24) acupoints could improve cognitive function and enhance
      spontaneous low-frequency brain activity in rats with ischemic stroke. METHODS:
      Total 36 rats were randomly divided into 3 groups-the sham surgery (Sham) group,
      the middle cerebral artery occlusion induced cognitive deficit (MICD) group, and
      the MICD with EA (MICD + EA) treatment group. The rats in MICD + EA group
      received EA treatment at DU20 and DU24 acupoints for 14 consecutive days after
      the surgery. The Morris water maze test was performed to assess the spatial
      learning and memory ability of the rats. Magnetic resonance imaging (MRI) was
      used to investigate the infarction volume and spontaneous low-frequency brain
      activity of each group. RESULTS: After EA for 14 days, the learning and memory
      ability of the MICD rats was improved, and the brain infarction volume was
      reduced. Furthermore, basing on the fMRI amplitude of low-frequency fluctuation
      (ALFF) analysis, the decreased ALFF of the MICD rats was found in auditory
      cortex, cingulate gyrus, lateral nucleus group of dorsal thalamus, hippocampus,
      motor cortex, prelimbic cortex, retrosplenial cortex, and sensory cortex compared
      with the rats in sham group. However, these suppressive regions were notably
      attenuated after EA treatment. CONCLUSIONS: Our results suggested that EA at DU20
      and DU24 acupoints could ameliorate cognitive impairment in rats with ischemic
      stroke, and the protective effect of EA may attribute to reactivating the
      cognition-related brain regions, such as hippocampus, retrosplenial cortex,
      cingulate gyrus, prelimbic cortex, and sensory cortex.

PMID- 30220309
TI  - Purpose: Focus the discussion and inform the debate.

PMID- 30220308
TI  - No one to turn to: low social support and the incidence of undesired pregnancy in
      the United States.
AB  - OBJECTIVE: Young women may experience social barriers to achieving their
      reproductive goals. This analysis explored whether low social support may
      contribute to the high incidence of undesired pregnancy in young women in the
      United States. STUDY DESIGN: Using 6 months of data from a prospective cohort of
      970 women ages 18-22 years in the United States, we described contraceptive use
      and applied multivariable logistic regression and standardization to estimate
      adjusted odds and absolute risk of undesired pregnancy among women reporting low
      social support versus higher social support. We investigated several measures of
      contraceptive use as possible explanations for this pathway. RESULTS: Sixty-five
      pregnancies were reported in the 6 months of the study, of which 30 (46%) were
      classified as undesired prior to conception. Among young women who reported low
      social support, 8% reported an undesired pregnancy during the study period as
      compared to 3% of the young women who reported higher levels of social support.
      Among non-black women, those who reported low social support had nearly seven
      times the odds of an undesired pregnancy as compared to women who reported higher
      social support (aOR: 6.8, 95%CI: 1.7, 27.1). We found no association between
      social support and undesired pregnancy among young black women. Contraceptive
      method use differed by social support at baseline, and throughout follow-up.
      CONCLUSIONS: Low social support - defined as the feeling of not having anyone to
      turn to - may be a risk factor for persistently high levels of undesired
      pregnancy among young women in the U.S. This association may be driven by
      differences in contraceptive use by level of social support. IMPLICATIONS:
      Interventions to increase young women's perceptions of social support may reduce
      the risk of undesired pregnancy for some individuals.

PMID- 30220310
TI  - Re: Obesity and place: Chronic disease in the 500 largest U.S. cities.

PMID- 30220307
TI  - Tissue-targeted complement therapeutics.
AB  - Complement activation contributes to the pathogenesis of numerous inflammatory
      and autoimmune diseases. Therapeutic complement inhibitors have proven effective
      in several of these diseases and have now entered clinical use. Complement
      activation has multiple different biologic effects, however, and the currently
      available drugs can have undesirable side-effects, such as an increased risk of
      infection. Several different complement inhibitors have been developed that bind
      to target molecules, thereby concentrating the drug at a specific anatomic site.
      This approach appears to be both more effective than untargeted drugs and to have
      fewer side effects. In this article we review different targeting strategies that
      have been developed and the evidence supporting the use and benefits of targeted
      drugs.

PMID- 30220312
TI  - Midwifery education.

PMID- 30220311
TI  - Response to Feldman.

PMID- 30220313
TI  - Adjuvant radiation for T1-2N1 oral cavity cancer survival outcomes and
      utilization treatment trends: Analysis of the SEER database.
AB  - OBJECTIVE: Evaluate current practice patterns in the use of adjuvant radiation
      for T1-2N1 OCSCC patients and investigate its efficacy in the population-based
      setting. MATERIALS AND METHODS: This study extracted patients who were treated
      surgically for T1N1 and T2N1 OCSCC without adverse nodal features from the SEER
      database from 2004 to 2013. Patients with distant metastatic disease, unknown
      surgery or radiation status, or prior malignancies were excluded. Patients were
      divided into those who underwent surgical resection with and without adjuvant
      radiation. Disease-specific survival (DSS) and overall survival (OS) were the
      primary outcomes measured. RESULTS: 746 patients met inclusion criteria and 70%
      received adjuvant radiation therapy. Treatment with adjuvant radiation therapy
      was significantly associated with improved 5-year DSS (65% versus 51%; p < 0.001)
      and OS (54% versus 44%; p = 0.007) for T1N1 tumors. Likewise, improved 5-year DSS
      (58% versus 38%; p = 0.009) and OS (48% versus 28%; p = 0.004) was shown in T2N1
      tumors. Patients with T2N1 tumors wer significantly more likely to receive
      adjuvant radiation (75% versus 63%; p < 0.001). Those with insurance and high
      risk primary subsites: buccal, retromolar trigone, and hard palate were more
      likely to receive adjuvant radiation. The percent utilization of adjuvant
      radiation remained constant through the study period for T2N1 tumors (72-74%) but
      significantly decreased for T1N1 (71-55%) (p = 0.047). CONCLUSION: Adjuvant
      radiation therapy is independently associated with a significant survival benefit
      for patients with both T1N1 and T2N1 OCSCC. However, this study demonstrates that
      patients with T1N1 cancer are less likely to receive adjuvant radiation and
      utilization is decreasing.

PMID- 30220314
TI  - Risk-reductive dental strategies for medication related osteonecrosis of the jaw
      among cancer patients: A systematic review with meta-analyses.
AB  - The purpose of this systematic review with meta-analysis was to assess the
      effectiveness of dental interventions in preventing or reducing the incidence of
      medication-related osteonecrosis of the jaw (MRONJ) in cancer patients receiving
      antiresorptive therapy, compared to similar control groups receiving no
      intervention. Randomized controlled trials (RCT), case-controls and cohorts on
      cancer patients with primary outcome being the prevalence of MRONJ were included.
      Four electronic databases were searched (Cochrane Library, PubMed, EMBASE and Web
      of Science) up to February 12, 2018. A total of 409 abstracts were assessed and
      one case-control, one RCT and four cohort studies with 2332 cancer patients met
      our inclusion criteria. Risk of bias analysis followed Cochrane's handbook. Risk
      of bias was unclear for the case-control study and high risk for the RCT and all
      cohort studies. Five studies utilized preventive measures consisting of an
      initial examination and performing all necessary dental treatment before patients
      initiated antiresorptive therapy; one study used specialized post-extraction
      protocols utilizing plasma-rich in growth factors (PRGF) on cancer patients
      receiving antiresorptive therapy. Though dental preventive measures decreased
      MRONJ incidence by 77.3% in six studies with 2332 cancer patients (95% CI = 47.4
      90.2%; p = .001) compared to control groups, quality of the evidence was low due
      to high or unclear risk of bias and the observational nature of five of the
      included studies. In conclusion, high-quality long-term prospective large sample
      size studies are needed to confirm these results due to high risk of bias and
      heterogeneous interventions. No funding.

PMID- 30220315
TI  - The Spider Limb Positioner in subscapular system free flaps.
AB  - BACKGROUND: The subscapular system is a versatile vascular network that can
      provide multiple flaps for reconstruction of the head and neck. A significant
      drawback of using the subscapular system is that patient positioning can preclude
      the use of simultaneous two-team ablative and reconstructive surgery. Herein, we
      describe a novel use of an upper extremity limb positioner (Spider Limb
      Positioner) used primarily in orthopedic surgery to facilitate concurrent two
      team technique in head and neck surgery. METHODS: Using a bean bag and the Spider
      Limb Positioner for the upper extremity, a semidecubitus position was used for
      subscapular donor site dissection. Ablative and reconstructive teams worked
      concurrently in all cases. RESULTS: This technique was utilized 78 times on 73
      patients, with chimeric flaps used in 38% of cases. The average operative time
      was 466 min. Only one patient required repositioning intraoperatively due to a
      change in the subscapular donor site side. There were no nerve compression
      injuries or positioning related complications. CONCLUSION: Scapular and
      parascapular free flaps are useful tools for reconstruction of the head and neck.
      In a two-team approach, the use of a semidecubitus position in conjunction with
      the Spider Limb Positioner facilitates exposure for the reconstructive team
      without compromising access for the ablative team.

PMID- 30220316
TI  - Radiologic predictors of immune checkpoint inhibitor response in advanced head
      and neck squamous cell carcinoma.
AB  - Radiologic predictors of response to immune checkpoint blockade (ICPi) in
      advanced head and neck squamous cell carcinoma (HNSCC) patients could help guide
      patient selection and management. We analyzed a large institutional cohort of 100
      consecutive HNSCC patients treated with ICPi to investigate associations between
      molecular and radiologic phenotype and assess radiologic predictors of response
      and survival. Of particular interest was the impact of increased total tumor
      burden (TB), calculated as the sum of the largest diameter of all measurable
      lesions according to RECIST 1.1, and early radiologic indicators of response
      versus progression. Within our cohort, 42% of patients had HPV+ associated
      disease, 64% had persistent/recurrent head and neck lesions, and 77% had distant
      metastases. Median TB was 5.4 cm. HPV+ disease and increased total mutational
      burden were associated with distant disease in the absence of locoregional
      disease (p < 0.01 and p = 0.03, respectively). Forty patients (40%) demonstrated
      clinical benefit to ICPi, and the median overall survival (OS) on PD-1 therapy
      was 4.5 months. A lower tumor burden at baseline was associated with clinical
      benefit (p = 0.03) and improved OS (p < 0.01, HR 2.33). There was only one
      instance of pseudoprogression; indeed any increase in TB on first interval scan
      was associated with poor OS (p = 0.02, HR 2.39). These data suggest that HNSCC
      patients who benefit from ICPi are more likely to have lower tumor burden at the
      onset of treatment and minimal increase in tumor burden while on treatment.

PMID- 30220318
TI  - The impact of institutional clinical trial recruitment versus hospital volume on
      survival outcomes of patients with head and neck cancer: An analysis of the PET
      NECK trial outcomes, UKCRN portfolio, and Hospital Episode Statistics (HES) in
      England.
AB  - OBJECTIVES: High institutional clinical trial recruitment and high hospital
      volume are reported to be independent indicators of better patient outcomes
      following cancer treatment. However, their relationship in head and neck cancers
      (HNC) remains less clear. METHODS: We aimed to assess the relationship between
      institutional clinical trial recruitment, hospital throughput of HNC cases, and
      survival of patients with advanced HNC treated with primary chemoradiotherapy at
      hospitals which recruited to the PET-NECK trial (2008-2012). The impact on
      outcome was assessed using Cox's proportional hazards regression analysis and
      multivariate analysis. RESULTS: HNC RCT recruitment positively correlated with
      hospital throughput (r = 0.57, p < 0.0001). Low-recruiters (1-5 patients) had a
      107% increased risk of death when compared to high-recruiters (>5 patients) (HR =
      2.07, p = 0.05). There was no significant impact of hospital throughput on
      overall or disease-specific HNC survival. Multivariate analysis identified p16
      status, N-stage, smoking, and RCT recruitment volume as the only significant
      predictors of survival. There was a significant difference in chemotherapy
      regimen between low and high-recruiters (p = 0.003) where a higher proportion of
      patients (50%, n = 13) in low-recruiting compared to high-recruiting hospitals
      (29%, n = 92) received neoadjuvant chemotherapy. A higher proportion of these
      patients died at low-recruiting hospitals (46% versus 23%). DISCUSSION: A
      significant association exists between high recruitment and better OS for
      patients with HNC. However, no significance was found between hospital throughput
      and outcomes. The significance of individual centre differences in chemotherapy
      regimen needs further investigation. Future studies need a greater number of
      patient outcome events to support the trends found in this study.

PMID- 30220317
TI  - Patterns of failure in high-metastatic node number human papillomavirus-positive
      oropharyngeal carcinoma.
AB  - BACKGROUND: The 8th edition American Joint Committee on Cancer staging system for
      resected HPV-positive oropharynx carcinoma (HPV+ OPC) highlights high node number
      as a critical determinant of survival. We sought to characterize outcomes and
      patterns of failure in patients with high pathologically involved node number
      oropharynx cancer. METHODS: We retrospectively identified 116 HPV+ OPC patients
      sequentially treated with neck dissection and either resection or intraoperative
      brachytherapy of the primary tumor between 2010 and 2016. External beam radiation
      was given based on the pathologic findings. Cox proportional hazards regression
      was used for multivariate analysis. RESULTS: With a median follow-up of 27
      months, the 3-year overall survival and progression free survival (PFS) were 89%
      and 81%, respectively. On multivariate analysis, >=5 involved lymph nodes was
      significantly associated with worse PFS (hazard ratio 4.3, 95% confidence
      interval (CI) 1.5-12.0, P = 0.001). Rates of 3-year locoregional recurrence (LRR)
      in patients with <=4 vs >=5 were 6% and 22% (log-rank P = 0.12). Rates of 3-year
      distant metastases (DM) were 12% and 53% between <=4 and >=5 (log-rank P <
      0.001). CONCLUSION: Our findings confirm that patients with 5 or more involved
      lymph nodes appear to have substantially worsened rates of disease recurrence.
      While these patients appear to be at high risk of both LRR and DM, the
      predominant mechanism of failure is distant, and the rate of DM in this group was
      over 50%. Dedicated clinical trials in this patient population are warranted with
      a focus on mitigating the high DM rate.

PMID- 30220319
TI  - Three distinct genomic subtypes of head and neck squamous cell carcinoma
      associated with clinical outcomes.
AB  - OBJECTIVES: Heterogeneity of head and neck squamous cell carcinomas (HNSCCs)
      results in unpredictable outcomes for patients with similar stages of cancer.
      Beyond the role of human papilloma virus (HPV), no validated molecular marker of
      HNSCCs has been established. Thus, clinically relevant molecular subtypes are
      needed to optimize HNSCC therapy. The purpose of this study was to identify
      subtypes of HNSCC that have distinct biological characteristics associated with
      clinical outcomes and to characterize genomic alterations that best reflect the
      biological and clinical characteristics of each subtype. MATERIALS AND METHODS:
      We analyzed gene expression profiling data from pan-SCC tissues including
      cervical SCC, esophageal SCC, lung SCC, and HNSCC (n = 1346) to assess the
      similarities and differences among SCCs and to identify molecular subtypes of
      HNSCC associated with prognosis. Subtype-specific gene expression signatures were
      identified and used to construct predictive models. The association of the
      subtypes with prognosis was validated in two independent cohorts of patients.
      RESULTS: Pan-SCC analysis identified three novel subtypes of HNSCC. Subtype 1 had
      the best prognosis and was similar to cervical SCC, whereas subtype 3 had the
      worst prognosis and was similar to lung SCC. Subtype 2 had a moderate prognosis.
      The 600-gene signature associated with the three subtypes significantly predicted
      prognosis in two independent validation cohorts. These three subtypes also were
      associated with potential benefit of immunotherapy. CONCLUSION: We identified
      three clinically relevant HNSCC molecular subtypes. Independent prospective
      studies to assess the clinical utility of the subtypes and associated gene
      signature are warranted.

PMID- 30220321
TI  - Clinical perineural invasion of cutaneous head and neck cancer: Impact of
      radiotherapy, imaging, and nerve growth factor receptors on symptom control and
      prognosis.
AB  - OBJECTIVES: Clinical perineural invasion (CPNI) of cutaneous head and neck cancer
      is associated with poor prognosis and presents a therapeutic dilemma. The purpose
      of this study was to determine the relationship between CPNI and nerve growth
      factor receptors (NGFR), and the impact of radiotherapy (RT), imaging, and NGFR
      on symptom control and disease-related outcomes. MATERIALS AND METHODS: We
      retrospectively reviewed patients with CPNI of cutaneous head and neck cancer who
      were treated with RT between 2010 and 2015 at our institution. Exact chi-square
      and Wilcoxon rank-sum tests compared patients with positive versus negative
      staining for TrkA and/or CD271. Gray's test determined differences in cumulative
      incidences of 1- and 2-year locoregional recurrence (LRR) and cancer-specific
      mortality (CSM). RESULTS: Twenty-three patients had a median overall follow-up of
      31.4 months from initial clinical symptoms and 19.7 months from pathological
      confirmation of PNI. The most prevalent symptoms were numbness (70%) and pain
      (57%). Sixteen patients (70%) experienced symptom improvement or control,
      especially decreased pain (85%), within a median of 2.6 months from starting RT.
      The 1- and 2-year rates of overall LRR were 37% and 71%, while those of overall
      CSM were 11% and 25%, respectively. Patients who stained positively for TrkA
      and/or CD271 had significantly worse LRR compared to patients who stained
      negatively for both markers (p = 0.046). CONCLUSION: Positive TrkA and/or CD271
      staining predicts worse outcomes. Patients may benefit from aggressive RT for
      local control and symptom improvement. Future research is needed to identify the
      potential for anti-nerve growth factor therapies in CPNI.

PMID- 30220320
TI  - Odontogenic carcinosarcoma: A systematic review.
AB  - The aim of this study was to integrate the available data published on
      odontogenic carcinosarcoma into a comprehensive analysis of their features,
      treatment and recurrence. An electronic search with no publication date or
      language restriction was undertaken in March 2018 in the following databases:
      Medline Ovid, PubMed, Web of Science, Scopus and LILACS. Eligibility criteria
      included publications having enough clinical, imaginological and
      histopathological information to confirm a definite diagnosis of the neoplasm.
      Data were evaluated descriptively and statistically using the MedCalc software.
      The Kaplan-Meier method was used for survival analysis. The systematic review
      detected nine articles from eight countries. Six cases with no age predilection
      occurred in male individuals complaining of painful swelling in the posterior
      mandible. Radiographically, the lesions were large, with expansive radiolucency
      and with ill-defined borders and seven cases were associated with preexisting
      odontogenic lesions. Radical surgery was the treatment of choice in the majority
      of cases. Recurrences (n = 6), metastasis (n = 4) and death (n = 4) were
      frequently observed in many cases. Odontogenic carcinosarcoma is a very
      aggressive neoplasm with a poor prognosis. This study provides knowledge that
      could help surgeons, oncologists, otorhinolaryngologists and oral maxillofacial
      pathologists with the diagnosis and management of these lesions.

PMID- 30220322
TI  - Protective effects of metformin, statins and anti-inflammatory drugs on head and
      neck cancer: A systematic review.
AB  - The main objective of this study was to evaluate the effect of metformin, statins
      and anti-inflammatory drugs (NSAIDs) on head and neck cancer (HNC). Specifically,
      the potential beneficial effects on risk, survival and recurrence based on
      epidemiological studies. PRISMA guidelines were followed. After searching MEDLINE
      (PubMed), IBECS, LILACS and the Cochrane Central Register for Controlled Trials,
      13 studies met the inclusion criteria and so underwent qualitative synthesis (six
      studies for metformin and seven for NSAIDs). No studies were found for statins.
      Studies varied in their methodological quality. Meta-analyses showed that
      metformin exerts significant beneficial effects on HNC risk (RR = 0.71 95% CI
      0.61-0.84) and overall survival (RR = 1.71 95% CI 1.20-2.42). Qualitative
      synthesis also suggests an apparently dose-response relationship and increased
      benefit when administered alone. The pooled-analyses yielded an almost
      significant effect of NSAIDs on HNC risk (RR = 0.86 95% CI 0.74-1.01). No
      associations were found between aspirin use and the risk of HNC (RR = 0.98 95% CI
      0.77-1.24) and overall survival (RR = 1.10 95% CI 0.89-1.36). Metformin appears
      to have beneficial effects on HNC risk and overall survival, with an apparently
      dose-response relationship and increased benefit when administered alone. NSAIDs
      also seem to have a modest beneficial effect on HNC risk. No definitive
      conclusions can be reached for aspirin as the evidence available was proved
      inconsistent. Further research by means of well designed and conducted studies
      are needed to determine firm clinical implications. Standardized assessment
      methods for HNC outcomes should be established and account for known confounding
      factors such as smoking and alcohol consumption.

PMID- 30220323
TI  - Temporal lobe injury patterns following intensity modulated radiotherapy in a
      large cohort of nasopharyngeal carcinoma patients.
AB  - OBJECTIVES: To analyze the correlation between dose-volume-histograms (DVHs) with
      three patterns (edema, enhancement, and necrosis) of temporal lobe injury (TLI)
      in patients receiving intensity modulated radiation therapy (IMRT) for
      nasopharyngeal carcinoma (NPC) and to determine optimal thresholds to predict the
      incidence of each TLI pattern, with particular emphasis on the relationship
      between edema volume and the risk of enhancement and necrosis. MATERIALS AND
      METHODS: A cohort of 4186 NPC patients treated with IMRT was retrospectively
      reviewed with TLI presenting in 188 patients. The atlases of complication
      incidence (ACI) for each pattern were constructed using DVH curves of temporal
      lobes. Optimal threshold for predicting incidence of each pattern was determined
      using the point closest to top-left of the plot. The accuracy of using edema
      volume to predict enhancement and necrosis incidence was evaluated via area under
      curve (AUC) of receiver operator characteristics (ROC). RESULTS: All DVH
      parameters, Dmean, Dmax, D0.25cc, D0.5cc, D1cc, D3cc, D6cc, V20Gy, V30Gy, V40Gy,
      V50Gy, V60Gy, and V70Gy, except Dmin showed statistically significant differences
      between subgroups of each pattern (p < 0.05). For predicting incidence of each
      pattern, optimal DVH thresholds over the range of D0.25-D1cc, Dmean and V20-V70
      were derived. The optimal thresholds of edema volume for predicting enhancement
      were 0.96 and 2.2cc and for predicting necrosis were 0.94 and 11.5cc. CONCLUSION:
      Optimal DVH thresholds were generated for limiting risk of each injury pattern.
      Edema volume was a strong predictor for risk of enhancement and necrosis, which
      could potentially be reduced by lowering edema volume below threshold.

PMID- 30220324
TI  - Prognostic implications of the 8th edition American Joint Committee on Cancer
      (AJCC) staging system in oral cavity squamous cell carcinoma.
AB  - BACKGROUND: The American Joint Committee on Cancer (AJCC) has changed the staging
      system of oral squamous cell carcinoma (OSCC) in the 8th edition of its staging
      manual to include depth of invasion (DOI) of the primary tumor as a modifier to
      the T category and extranodal extension (ENE) to upstage node positive OSCC. This
      study aims to evaluate the performance of the AJCC 8 pathologic staging system in
      OSCC and compare it to its predecessor (AJCC 7). METHODS: Analysis of 663
      patients with OSCC from a prospective database was performed using the Cox
      proportional hazards competing risk model. The prognostic performance of the
      pathologic staging system was assessed using the Akaike Information Criterion
      (AIC) and Harrell's concordance index (C-index). RESULTS: AJCC 8 led to upstaging
      of 35.6% (N = 235) of patients in this cohort. Both AJCC 7 and 8 show limited
      monotonicity and poor stratification between stage groups I to III. The estimates
      for model performance reveal that AJCC 8 has modest predictive capacity for
      overall survival (OS) and disease specific survival (DSS) (Harrell's C of 0.70
      and 0.74, respectively) but is superior to AJCC 7 (Harrell's C of 0.65 and 0.69,
      respectively). CONCLUSIONS: The AJCC 8 staging system is more complex than its
      former version due to the inclusion of DOI and ENE. Compared with AJCC 7, it
      performs better in stratifying survival of OSCC patients by stage.

PMID- 30220326
TI  - The efficacy of induction chemotherapy in the treatment of stage II
      nasopharyngeal carcinoma in intensity modulated radiotherapy era.
AB  - PURPOSE: To evaluate the efficacy of induction chemotherapy in the treatment of
      stage II nasopharyngeal carcinoma (NPC) in era of intensity modulated
      radiotherapy (IMRT). METHODS AND MATERIALS: A total of 173 patients with American
      Joint Committee on Cancer (AJCC) 7th stage II NPC from two institutions were
      included. All patients were divided into two groups: induction chemotherapy +
      concurrent chemoradiotherapy group (ICRT) group and concurrent chemoradiotherapy
      group (CCRT). Induction chemotherapy was consisted of one to three cycles of
      cisplatin plus fluorouracil (PF) or paclitaxel plus cisplatin (TP). Concurrent
      chemotherapy included one to three cycles of cisplatin. We retrospectively
      assessed overall survival (OS), progression-free survival (PFS), locoregional
      failure free survival (LRFFS) and distant metastasis free survival (DMFS) in
      patients of both groups. T-test, Chi-square test, Kaplan-Meier methodology and
      Cox proportional hazards model were used to analyze. RESULTS: With a median
      follow up of 64.7 months, no significant difference was found in grade 3-4
      hematologic toxicity, liver dysfunction and renal impairment between ICRT and
      CCRT group. Univariable analyses shown adding induction chemotherapy to CCRT
      significantly decreased 5-year OS (87.9% vs 95.5%, P = 0.033), 5-year PFS (74.0%
      vs 86.1%, P = 0.035), 5-year LRFFS (80.0% vs 91.2%, P = 0.016), but there was no
      statistically significant difference in 5-year DMFS (87.1% vs 94.7%, P = 0.095).
      In multivariable analyses, we found the consistent results that induction
      chemotherapy was a negative factor associated with OS (HR of death = 3.768, 95%
      CI = 1.117-12.709; P = 0.032), PFS (HR of progression = 2.156, 95% CI = 1.060
      4.386; P = 0.034), LRFFS (HR of locoregional relapse = 2.435, 95% CI = 1.009
      5.874; P = 0.048) and also DMFS (HR of metastasis = 2.873, 95% CI = 1.005-8.211;
      P = 0.049), in stage II NPC patients. CONCLUSION: In present study, we found that
      induction chemotherapy caused deleterious effect on stage II NPC patients.
      However, this is a retrospective study and the adverse effects of induction
      chemotherapy has not been previously reported. It warrants further investigation.

PMID- 30220327
TI  - Why does a steep caudal-rostral gradient exist in glycine content in the brain?
AB  - Glycine is an important amino acid in the central nervous system. Interestingly,
      the content of glycine is about 9 times higher in the spinal cord grey matter
      than in the telencephalon. And this kind of caudal to rostral gradient is never
      seen in any other neurotransmitters. However, the cause of this phenomenon
      remains unknown. In the present report, I, thus, postulate the following theory.
      Glycine has dual roles as a neurotransmitter, one is the agonist for inhibitory
      glycine receptors (GlyRs), and the other is a co-agonist for excitatory NMDA
      receptors (NMDARs). Inhibitory GlyRs are concentrated in the lower brain and the
      affinity of glycine to GlyRs is low, leading to the high content of glycine in
      the lower brain. In contrast, in the upper brain, there are little glycinergic
      neurons and the affinity of glycine to NMDARs is very high, leading to the low
      content of glycine in the forebrain. These different roles of glycine as a
      neurotransmitter between in the upper brain and in the lower brain make this
      steep caudal-rostral gradient in glycine content.

PMID- 30220325
TI  - DNA methylation derived systemic inflammation indices are associated with head
      and neck cancer development and survival.
AB  - OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is often associated
      with chronic systemic inflammation (SI). In the present study, we assessed if DNA
      methylation-derived SI (mdSI) indices: Neutrophil-to-Lymphocyte ratio (mdNLR) and
      Lymphocyte-to-Monocyte ratio (mdLMR) are associated with the presence of HNSCC
      and overall survival (OS). MATERIALS AND METHODS: We used two peripheral blood
      DNA methylation datasets: an HNSCC case-control dataset (n = 183) and an HNSCC
      survival dataset (n = 407) to estimate mdSI indices. We then performed
      multivariate regressions to test the association between mdSI indices, HNSCC
      development and OS. RESULTS: Multivariate logistic regression revealed that
      elevated mdNLR was associated with increased odds of being an HNSCC case (OR =
      3.25, 95% CI = 2.14-5.34, P = 4 * 10-7) while the converse was observed for mdLMR
      (OR = 0.88, 95% CI = 0.81-0.90, P = 2 * 10-3). In the HNSCC survival dataset,
      HPV16-E6 seropositive HNSCC cases had an elevated mdLMR (P = 9 * 10-5) and a
      lower mdNLR (P = 0.003) compared to seronegative patients. Multivariate Cox
      regression in the HNSCC survival dataset revealed that lower mdLMR (HR = 1.96,
      95% CI = 1.30-2.95, P = 0.0013) but not lower mdNLR (HR = 0.68, 95% CI = 0.46
      1.00, P = 0.0501) was associated with increased risk of death. CONCLUSION: Our
      results indicate that mdSI estimated by DNA methylation data is associated with
      the presence of HNSCC and overall survival. The mdSI indices may be used as a
      valuable research tool to reliably estimate SI in the absence of cell-based
      estimates. Rigorous validation of our findings in large prospective studies is
      warranted in the future.

PMID- 30220328
TI  - The pertussis hypothesis: Bordetella pertussis colonization in the etiology of
      asthma and diseases of allergic sensitization.
AB  - Decades of peer reviewed evidence demonstrate that: 1)Bordetellapertussisand
      pertussis toxin are potent adjuvants, inducing asthma and allergic sensitization
      in animal models of human disease, 2)Bordetella pertussisoften colonizes the
      human nasopharynx, and is well documented in highly pertussis-vaccinated
      populations and 3) in children, a history of whooping cough increases the risk of
      asthma and allergic sensitization disease. We build on these observations with
      six case studies and offer a pertussis-based explanation for the rapid rise in
      allergic disease in former East Germany following the fall of the Berlin Wall;
      the current asthma, peanut allergy, and anaphylaxis epidemics in the United
      States; the correlation between the risk of asthma and gross national income per
      capita by country; the lower risk of asthma and allergy in children raised on
      farms; and the reduced risk of atopy with increased family size and later sibling
      birth order. To organize the evidence for the pertussis hypothesis, we apply the
      Bradford Hill criteria to the association between Bordetella pertussisand asthma
      and allergicsensitization disease. We propose that, contrary to conventional
      wisdom that nasopharyngealBordetella pertussiscolonizing infections are harmless,
      subclinicalBordetella pertussiscolonization is an important cause of asthma and
      diseases of allergic sensitization.

PMID- 30220329
TI  - Accuracy of movement quality screening to document effects of neuromuscular
      control retraining exercises in a young ex-footballer with hip and groin
      symptoms: A proof of concept case study.
AB  - Hip and groin pain is common in footballers and altering movement patterns can
      reduce symptoms. Observational tests of movement control are thought to identify
      abnormal movement patterns, but their accuracy needs yet to be confirmed by
      comparison with an objective measure. To assess the accuracy, using 3D motion
      analysis, of observational movement control tests and their ability to detect
      changes, and document changes in symptoms following a neuromuscular control
      exercise programme in an ex-footballer with hip and groin pain. A 25-year-old
      male with chronic bilateral hip and groin pain had their movement control ability
      rated and kinematic data collected using 3D motion analysis while performing
      Small Knee Bend (SKB) and SKB with Rotation (SKB Rot) tests pre-and post
      neuromuscular control exercise training. Movement control was rated as at fault
      if they were unable to control specific trunk and pelvic movements during the
      tests. The Copenhagen Hip and Groin Outcome Score (HAGOS) was used to assess
      symptoms. Following the intervention, observational rating during the SKB test
      improved from fault to no fault for anterior pelvic tilt, which decreased by 17
      degrees  and 16 degrees  during right and left leg SKB tests respectively. The
      HAGOS symptoms subsection improved from 36% to 61%. Observational movement
      screening ratings were supported by 3-D motion analysis. These findings indicate
      that the screening tool was accurate for detecting improvements in trunk and
      pelvic movement control following an exercise programme in an ex-footballer who
      had presented with hip and groin pain.

PMID- 30220330
TI  - Cancer follows chromosome missegregation when all endogenous repair mechanisms
      fail.
AB  - Almost all solid tumors consist of aneuploid cells with highly abnormal
      chromosome numbers. Such cancer cells could very well originate from chromosome
      missegregation which is a disturbingly common phenomenon, happening in 0.01 to 4
      percent of cell divisions. Missegregated cells are aneuploid, typically lacking a
      chromosome or having one in surplus. Missegregated cells have mutation in the
      gene dose of the perhaps a thousand genes on a chromosome in one step. After
      missegregation cell division cannot be done right, as at least one daughter cell
      has a faulty chromosome number. At division in cells with surplus chromosomes the
      number will tend to increase due to mismatch in the division machinery. The
      organism has a number of repair mechanisms in place to prevent potential damage
      of accumulating aneuploidy. The first is the roll-back of the cell division
      itself, leading to tetraploidy or sometimes two nuclei in one cell; another is
      the prevention of further divisions. A very important one is induction of
      apoptosis, the cellular suicide. A special case is the elimination of the nucleus
      itself in the formation of red blood cells. Many aneuploid cells are probably
      eliminated by the immune system. A hypothetical mechanism would be the prevention
      of metastasis. Missegregation increases with age when the chromosomes lose their
      protective telomere ends at the Hayflick limit after about 50 divisions, and the
      unraveled chromosomes fuse and break. For cancer to develop all of these repair
      mechanisms must fail. The hypothesis offers a straightforward rationale for the
      multiple hit hypothesis of cancer development.

PMID- 30220331
TI  - Recurrent bacterial translocation from gut and sepsis in Head and neck cancer
      patients and its prevention by probiotics.
AB  - Head and neck cancers are the 6th most common cancer type in human malignant
      tumors and treated with chemoradiotherapy and surgery. Chemotherapy during these
      treatment modalities leads to damage of intestinal epithelial barriers and
      results in translocation of intestinal bacteria in bloodstream through invasion
      in these damaged regions. In this report, we report two cases of hypopharyngeal
      cancer patients, both of whom received chemotherapy before surgery. The patients
      demonstrated repeated sepsis before and after surgery, supporting translocation
      of intestinal bacteria. Proper continuous probiotic use prevented proliferation
      and intestinal bacterial translocation. Hypothesis of bacterial translocation and
      prevention by probiotics are discussed.

PMID- 30220332
TI  - A new theory on GABA and Calcitonin Gene-Related Peptide involvement in Mal de
      Debarquement Syndrome predisposition factors and pathophysiology.
AB  - INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a condition characterized by
      a sensation of motion in the absence of a stimulus, which presents with two
      subtypes depending on the onset: Motion-Triggered, and Spontaneous or Non-Motion
      Triggered. MdDS predominantly affects women around 40-50 years of age and a high
      number of patients report associated disorders, such as migraine and depression.
      The pathophysiology of MdDS is unclear, as is whether there are predisposing
      factors that make individuals more vulnerable to developing the condition.
      Hormonal changes in women similarly to what observed in migraineous patients, as
      well as depression disorder, have been examined as potential key factors for
      developing MdDS. Studies on migraine and depression have revealed correlations
      with hormonal fluctuations in females as well as aberrant levels of some key
      neurotransmitters such as Gamma-Aminobutyric Acid (GABA) and inflammatory
      neuropeptides like Calcitonin Gene-Related Peptide (CGRP). Consequently, this
      manuscript aims to propose a new hypothesis on the predisposing factors for MdDS
      and a new concept that could contribute to the understanding of its
      pathophysiology. NEW HYPOTHESIS: Recent findings have demonstrated a role for
      hormonal influences in MdDS patients, similar to previous observations in
      patients with depression and migraine. We hypothesize the involvement of gonadal
      hormones and aberrant neurotransmitter levels, including the GABAergic and
      serotonergic systems, in MdDS pathophysiology. Our theory is that certain
      individuals are more vulnerable to develop MdDS during specific gonadal hormonal
      phases. Furthermore, we hypothesize that it may be possible to identify these
      individuals by measurement of an existing imbalance of these neurotransmitters or
      inflammatory neuropeptides like CGRP. FURTHER EVALUATION OF THE HYPOTHESIS:
      According to one theory, MdDS is considered as a maladaptation of the Vestibular
      Ocular Reflex (VOR) and velocity storage. When considering this theory, it is
      essential to highlight that the brainstem nuclei involved in the VOR and the
      velocity storage include GABAb sensitive neurons, which appear to produce
      inhibitory control of velocity storage. Responses of these GABAb sensitive
      neurons are also modulated by CGRP. Thus an alteration of the GABAergic network
      by imbalances of inhibitory neurotransmitters or CGRP could influence signal
      integration in the velocity storage system and therefore be directly involved in
      MdDS pathophysiology. CONSEQUENCE OF THE HYPOTHESIS AND FUTURE STUDIES: A
      hormonal and neurotransmitter imbalance may act to predispose individuals in
      developing MdDS. Future studies should focus on the hormonal influences on
      neurotransmitters (e.g. GABA) and on the trial of CGRP antagonist drugs for the
      treatment of MdDS patients.

PMID- 30220333
TI  - ADHD-originating in the gut? The emergence of a new explanatory model.
AB  - The microbiome-gut-brain axis paradigm explains that alterations in the central
      nervous system and behavior may be secondary to functional changes in the gut in
      general and more specifically the enteric nervous system. An unfavorable
      development of the intestinal microbial ecosystem, leading to e.g. a diminished
      microbial diversity, may play a central role. This paper outlines, and describes
      the theoretical basis of, a novel integrative model explaining the etiology and
      pathogenesis of ADHD in a microbiota-gut-brain context, taking into account the
      complexity of the bi-directional signaling between the gut and the brain.

PMID- 30220334
TI  - 'Give-up-itis' revisited: Neuropathology of extremis.
AB  - The term 'give-up-itis' describes people who respond to traumatic stress by
      developing extreme apathy, give up hope, relinquish the will to live and die,
      despite no obvious organic cause. This paper discusses the nature of give-up
      itis, with progressive demotivation and executive dysfunction that have clinical
      analogues suggesting frontal-subcortical circuit dysfunction particularly within
      the dorsolateral prefrontal and anterior cingulate circuits. It is hypothesised
      that progressive give-up-itis is consequent upon dopamine disequilibrium in these
      circuits, and a general theory for the cause and progression of give-up-itis is
      presented in which it is proposed that give-up-itis is the clinical expression of
      mental defeat; in particular, it is a pathology of a normal, passive coping
      response.

PMID- 30220335
TI  - Visceral theory of sleep and origins of mental disorders.
AB  - Visceral theory of sleep states that the same brain neurons, which process
      external information in wakefulness, during sleep switch to the processing of
      internal information coming from various visceral systems. Here we hypothesize
      that a failure in the commutation of exteroceptive and interoceptive information
      flows in the brain can manifest itself as a mental illness.

PMID- 30220336
TI  - Intermittent living; the use of ancient challenges as a vaccine against the
      deleterious effects of modern life - A hypothesis.
AB  - Chronic non-communicable diseases (CNCD) are the leading cause of mortality in
      developed countries. They ensue from the sum of modern anthropogenic risk
      factors, including high calorie nutrition, malnutrition, sedentary lifestyle,
      social stress, environmental toxins, politics and economic factors. Many of these
      factors are beyond the span of control of individuals, suggesting that CNCD are
      inevitable. However, various studies, ours included, show that the use of
      intermittent challenges with hormetic effects improve subjective and objective
      wellbeing of individuals with CNCD, while having favourable effects on
      immunological, metabolic and behavioural indices. Intermittent cold, heat,
      fasting and hypoxia, together with phytochemicals in multiple food products, have
      widespread influence on many pathways related with overall health. Until
      recently, most of the employed challenges with hormetic effects belonged to the
      usual transient live experiences of our ancestors. Our hypothesis; we conclude
      that, whereas the total inflammatory load of multi-metabolic and psychological
      risk factors causes low grade inflammation and aging, the use of intermittent
      challenges, united in a 7-10 days lasting hormetic intervention, might serve as a
      vaccine against the deleterious effects of chronic low grade inflammation and
      it's metabolic and (premature) aging consequences.

PMID- 30220337
TI  - Role of L-selectin on leukocytes in the binding of sialic acids on sperm surface
      during the phagocytosis of sperm in female reproductive tract.
AB  - In either natural fertilization or artificial insemination, hundreds of millions
      of sperm are ejaculated or inseminated and then deposited in the female
      reproductive tract, but only a few sperm reach the ampulla or the site of
      fertilization. This dramatic reduction in numbers clearly highlights the
      obstacles that sperm must overcome in order to reach the destination for egg
      fertilizing. Phagocytosis of sperm by leukocytes are repeatedly observed and
      generally considered to be one of the most important barriers, but the mechanism
      of the phagocytosis of sperm remains unclear. L-selectin is constitutively
      expressed on leukocytes, which can influence the behaviors of leukocytes when
      bind to ligands. Sialic acids are found as the outer most monosaccharide, capping
      the majority of glycans at the sperm surface, can act as recognition molecule.
      Since the sialic acids are considered as ligands of L-selectin, we propose that
      leukocytes bind to the sperm through the L-selectin on leukocytes and sialic acid
      on sperm surface during the sperm phagocytosis in female reproductive tract.

PMID- 30220338
TI  - Erickson health coaching: An innovative approach for weight management in obese
      patients with obstructive sleep apnoea?
AB  - Obstructive sleep apnoea (OSA) is a highly prevalent medical condition and amajor
      cardiovascular risk factor. Obesity is present in ~70% of patients with OSA,
      nevertheless, continuous positive airway pressure (CPAP) ventilation - the gold
      standard therapy for moderate and severe OSA - has no appreciable long-term
      beneficial effects on obesity, body composition, energy metabolism, physical
      activities or the incidence of major cardiovascular events. Therefore, effective
      weight loss strategies in conjunction with CPAP therapy in OSA are critically
      needed. Since lifestyle interventions may positively impact body weight, there is
      a strong rationale to testing the hypothesis that Erikson coaching intervention
      as a form of lifestyle intervention to obese patients with OSA may increase their
      adherence to healthy lifestyle behaviour and thus result in weight reduction,
      improved body composition (reduction in %body fat) and improvements in glucose
      and lipid metabolism. There are three lines of evidence to justify testing this
      hypothesis: First, health coaching significantly facilitates uptake of healthy
      behaviours across a broad variety of chronic conditions; second, several
      randomized clinical trials suggested positive impact of health coaching on weight
      management and on cardiometabolic risk factors in overweight/obese otherwise
      healthy persons; third, Erickson coaching approach empowers the three key
      elements of health coaching (patient-centeredness, patient-determined goals, use
      of a self-discovery process) further, namely by introducing two other specific
      core elements into the coaching process: a) solution-focus and outcome frame, b)
      orientation at the patient-formulated positive outcomes (i.e., positive values
      resulting from behavioural change). Importantly, results of our recent pilot
      observational cohort study suggested that Erickson coaching is a powerful tool to
      address behavioural modification in obesity. In conclusion, testing our
      hypothesis may have significant clinical implications: if clinical randomized
      trials indicate that Erickson health coaching is an efficient approach to
      behavioural change and weight management in OSA then combining Erickson coaching
      with CPAP therapy may result in reductions in cardiovascular morbidity and
      mortality in these high-risk patients.

PMID- 30220339
TI  - True nature of mild epithelial dysplasia in oral lichenoid mucositis - Is it a
      reactionary change to the sub-epithelial inflammation or represents true
      malignant potential? A hypothesis.

PMID- 30220340
TI  - Copper as the most likely pathogenic divergence factor between lung fibrosis and
      emphysema.
AB  - Although fibrosis and emphysema are in many ways on opposite ends of the
      pulmonary parenchymal disease spectrum, they seem to share common
      pathomechanistic steps. This is illustrated by the coexistence of both entities
      in lungs of individuals with combined pulmonary fibrosis and emphysema.
      Macroproteins elastin and collagen are major constituents of the pulmonary
      extracellular matrix. The prevailing paradigm states that emphysema is caused by
      an imbalance between destructive proteolytic and protective antiproteolytic
      enzymes leading to accelerated degradation of elastin fibers in the lungs. Rates
      of elastin breakdown, however, are equally enhanced in patients with idiopathic
      pulmonary fibrosis (IPF) and emphysema. Excessive accumulation of collagen is a
      hallmark of IPF. Surprisingly, collagen levels in the lung parenchyma of patients
      with emphysema are also higher than in controls. The concentration of elastin
      fibers is elevated in fibrotic lungs, despite accelerated elastinolysis,
      suggesting that elastin repair is also enhanced in IPF. Since elastin
      concentrations are reduced in emphysematous lungs, the factor of divergence
      between emphysema and fibrosis seems to be the degree of elastin repair. Multiple
      elastin repair steps can be deduced of which tropoelastin synthesis and
      crosslinking of tropoelastin polymers by the copper dependent enzyme lysyl
      oxidase seem to be the most important ones. We suspect that the distinction in
      the pathogeneses of lung fibrosis and emphysema depends on the local availability
      of copper to activate sufficient lysyl oxidase for elastin crosslinking, and
      suggest assessing the effects of inhalation therapy with copper plus heparin in
      emphysema and heparin monotherapy in IPF.

PMID- 30220341
TI  - Mucus protectors: Promising therapeutic strategies for inflammatory bowel
      disease.
AB  - Inflammatory bowel disease (IBD) is a group of intestinal non-specific
      inflammatory diseases with unclear pathogenesis, characterized with the impaired
      intestinal mucosal barriers and the activated immune system. Mucus layer is the
      vital protector over the intestinal epithelia cells (IECs). Mucus layer with
      impaired function could not provide isolated protection for IECs and thus
      proteases and pathogens from the gut lumen attacked and damaged the epithelial
      layer. Clinical manifestation and histopathology suggest that IBD might be a self
      digestive inflammatory disease caused by digestive enzymes. In this review, we
      specifically focus on the role of intestinal mucosal barriers and aim to
      summarize the relationship among mucus layer, self-digestion and inflammation in
      IBD. We also propose a "Two Hits" Self-Digestion theory to explain the role of
      self-digestion in IBD and assess the application of mucus protectors to treat
      IBD.

PMID- 30220343
TI  - Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate,
      but others do not?
AB  - Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic disease
      the pathogenesis of which remains elusive. Pragmatic proof-of-principle of the
      hypothetical mechanisms causing the clinical symptoms has been delivered, but it
      is hard to explain why some patients do respond favourably to treatment with
      sodium dichloroacetate (DCA), which enhances the activity of the mitochondrial
      enzyme pyruvate dehydrogenase, but other patients experience no benefit from this
      substance. In a prospective trial including 35 ME/CFS patients, logistic
      regression analysis with stepwise elimination has identified 6 pre-treatment
      characteristics allowing for the differentiation between responders (n = 13) and
      non-reponders (n = 22) with high accuracy (P < 0.0001; area under the ROC-curve =
      0.92). A formula was derived generating the probability of belonging to the group
      of responders. This finding may assist in selecting ME/CFS patients suitable for
      treatment with DCA, but requires further studies as to the predictive capacity of
      the derived formula.

PMID- 30220342
TI  - Should whole body cryotherapy sessions be differentiated between women and men? A
      preliminary study on the role of the body thermal resistance.
AB  - The aim of this study was to investigate how body thermal resistance between
      sexes evolves over time in the recovery period after a WBC session and to show
      how this parameter should be considered as a key parameter in WBC protocols.
      Eighteen healthy participants volunteered for the study (10 males and 8 females).
      Temperature (core and skin) were recorded pre- and post (immediately and every 5
      min until 35 min post) exposure to a single bout of WBC (30 s at -60  degrees C,
      150 s at -110  degrees C). From both core and skin temperatures a bio-heat
      transfer model was applied which led to the analytical formulation of the body
      thermal resistance. An unsteady behavior presenting a similar time-evolution
      trend in the body insulative response is shown for both females and males,
      possibly due to the vasodilatation process following an intense peripheral
      vasoconstriction during the extreme cold. Females present a 37% higher inner
      thermal resistance than males when reaching an asymptotical thermal state at rest
      due to a higher concentration of body fat percentage. Adiposity of tissues
      inherent in fat mass percentage appears to be a key parameter in the body thermal
      resistance to be taken into account in the definition of appropriate protocols
      for males and females. The conclusions of this preliminary study suggest that in
      order to achieve the same skin effects on temperature and consequently to cool
      efficiency tissues in the same way, the duration of cryotherapy protocols should
      be shorter when considering female compared to male.

PMID- 30220344
TI  - Selective sensitivity of the gut microbiome to iron chelators in polybacterial
      abdominal sepsis.
AB  - Iron chelation has been proposed as a potential therapy for polybacterial
      abdominal sepsis. Treatment with iron chelation is known to be able to attenuate
      bacterial growth. It is hypothesized that the different types of bacteria will
      exhibit variations in their sensitivity to iron chelation based on differences in
      their iron metabolism. Bacteria with weaker iron access systems might have their
      growth reduced initially, but stronger species may also be suppressed. Gram
      positive and Gram-negative bacteria are known to possess different iron
      acquisition systems, which may affect their response to iron chelation. Bacteria
      which can produce siderophores are at a particular advantage for iron
      acquisition. Novel iron chelators, which do not act as xenosiderophores, may be
      effective in depriving these bacteria of iron. This has implications for the
      treatment of polybacterial sepsis, which might be enhanced if the sensitivity to
      iron chelation of the primary causative agents is known.

PMID- 30220345
TI  - Noninvasive determination of the pulmonary artery input impedance.
AB  - A reliable noninvasive method for the estimation of pulmonary function in healthy
      and diseased subjects should be of great importance in the prognosis, diagnosis,
      and treatment of pulmonary hypertension. Here we propose such a method, which is
      based on the parameter identification of the five-element Windkessel model of
      pulmonary circulation. The method requires the following input variables: the
      heart rate, the stroke volume, the Doppler echocardiographic measurements of the
      tricuspid regurgitation and the pulmonary valve velocity profiles, and
      estimations of the right atrium and the pulmonary vein pressure. The stroke
      volume is calculated as a product of the left ventricle outflow tract area and
      the velocity-time integral measured at the same place. The model parameter
      identification procedure is based on minimization of the root mean square error
      between the pulmonary artery root pressure calculated from the aforementioned
      Doppler velocity profiles (from the Bernoulli equation applied during the
      ejection phase) and the pressure from the Windkessel model during the same
      period. The output from the model contains the calculated pulmonary artery input
      impedance (i.e. the model parameters: pulmonary vascular resistance, pulmonary
      artery proximal and distal compliances, inertance, and characteristic impedance)
      and the pulmonary artery pressure profile during the whole heart period. Our
      method is applied to a subject with pulmonary hypertension. The right heart Swan
      Ganz catheterization has been performed in this subject. The results obtained by
      using this method show that the five-element Windkessel model reconstructs the
      main features of the pulmonary artery input impedance very well: its modulus
      shows the minimum where the phase angle changes its sign. The pulmonary vascular
      resistance, the systolic, diastolic and mean pulmonary artery pressures obtained
      from the method are in good agreement with the values obtained invasively from
      the catheterization. Sensitivity analysis shows that the mean pulmonary pressure
      is fairly insensitive to slight overestimation/ underestimation of all input
      parameters, except for the right atrium pressure. The absolute error in the mean
      pulmonary artery pressure is nearly the same as the error in the right atrium
      pressure. Since the proposed method offers a deeper insight into the pulmonary
      circulation than the catheterization itself because it provides the proximal and
      distal compliance, the inertance and the characteristic impedance, it seems that
      it can serve in clinical practice as a good substitute for catheterization.

PMID- 30220346
TI  - Are sleep continuity disturbance and fatigue prodromal symptoms of cancer
      development?
AB  - Sleep continuity disturbance (also known as insomnia) and fatigue are common
      complaints of individuals diagnosed with cancer. Traditionally, many have
      believed that sleep continuity disturbance and fatigue are caused, in large
      measure, by the impact of the cancer diagnosis and treatment. Recent prospective
      research suggests however, that sleep continuity disturbance and fatigue may
      actually precede a cancer diagnosis. We suggest that sleep continuity disturbance
      and fatigue may in fact represent prodromal symptoms of cancer. We review the
      current perspectives of this sequence of events and present a revised schematic
      that accounts for the role of biological, behavioural, and cognitive factors that
      contribute to the development and maintenance of sleep continuity disturbances in
      cancer patients. Monitoring emergent and unexplained patient-reported fatigue,
      sleepiness, and insomnia may serve as early warning signs of new onset cancer,
      providing opportunity for early detection and early intervention.

PMID- 30220347
TI  - Rethinking the carcinogenesis of breast cancer: The theory of breast cancer as a
      child deficiency disease or a pseudo semi-allograft.
AB  - The theory of breast cancer as a child deficiency disease is an inversion of the
      current paradigm, which considers full-term pregnancies to be a protective factor
      and uses nulliparous women as the reference group. Instead, the theory of breast
      cancer as a child deficiency disease says that women with the highest parity
      (about 20, which is the limit of human fertility) are those with the lowest risk
      and should be used as the reference group in risk estimations. This theory is
      explained biologically by converting parity from the simple value of number of
      children into an understanding of the long-lasting biological and immunological
      effects of pregnancy. These effects can be reflected, as measured by functional
      genomics, in gene expression of the immune cells in the blood. Each pregnancy
      represents a unique fetus or semi-allograft, which provokes the creation and
      deposit of memory cell clones in the mother. Gene expression levels have been
      found to change linearly with number of full-term pregnancies in healthy women,
      but not in breast cancer patients. High hormone levels are necessary for a
      successful pregnancy, as they modulate the immune response from adaptive to
      innate in order to protect the fetus (considered as a semi-allograft) from
      rejection. At the end of the pregnancy, hormone levels drop, and the immune
      system recognizes the semi-allograft, but not in time for rejection to occur
      before birth. High hormones levels are also classified as carcinogens
      illustrating that carcinogenesis in the breast could be viewed as a war or
      balance between later exposures to hormonal carcinogens and the protection of the
      immune system. We propose that breast tumors are pseudo semi-allografts made up
      of transformed breast tissue cells. Assuming that the sensitivity to the exposure
      to increased levels of endogenous or exogenous hormones in women with breast
      cancer mimic those that occur in pregnancy, these breast tumor cells are
      protected against the body's immune reaction, just as the fetus is during
      pregnancy. However, with more pregnancies, the potential to eradicate the pseudo
      semi-allograft might increase due to enhanced immune surveillance. The theory of
      breast cancer as a child deficiency disease proposes that the protective effect
      of pregnancy on breast cancer incidence via the immune system is independent of
      other risk factors.

PMID- 30220348
TI  - Wheels-in-wheels: Use of gravity in human locomotion.
AB  - Although a wheel is an ideal method for transportation and the invention of the
      spoke wheel made a wheel lighter and swifter, a wheel cannot function well on
      slanted or rough surfaces; these are common in the natural environment. Further,
      the load support of the wheel is limited to a point of the whole wheel in contact
      with the ground. Then, we humans may be using the legs as a part of spoke wheel
      and place our legs and feet on the ground alternatively to support the body
      weight while the gravitational torque makes the center of mass (COM) rotate
      around the hip joint when proper stiffness and balance is made. Through a pulley
      like action involving the hamstrings and a lever-like action of back muscles via
      the psoas muscle, the energy expenditure for locomotion can be reduced to the
      energy for lifting the swing leg to maintain the proper position of the COM.
      Further, the stabilizing action of the psoas muscle to the spinal column can be
      achieved between the stance leg and the swing leg by the weight of the lifted
      swing leg during the forward movement. This lifting action during swing phase can
      assist an energy-efficient eccentric contraction of the stance leg. The passive
      tension generated by gravity (own weight and the carried load) can be the reason
      for the energy efficiency of both head-carrying and the Nepalese porter method.
      Using this passive gravitational force via actively synchronized neuromuscular
      action may be universal for animal locomotion.

PMID- 30220349
TI  - Modeling of complex signals in nerve fibers.
AB  - Experiments have demonstrated that signals in nerve fibers are composed by
      electrical and mechanical components. In this paper a coupled mathematical model
      is described which unites the governing equations for the action potential, the
      pressure wave in the axoplasm and the longitudinal and the transverse waves in
      the surrounding biomembrane into one system of equations. As a solution of this
      system, an ensemble of waves is generated. The main hypotheses of such a model
      are related to the nature of coupling forces between the single waves in the
      ensemble. These coupling forces are assumed to have bi-polar shapes leading to
      energetically stable solutions. The in silico modeling demonstrates the
      qualitative resemblance of computed wave profiles to experimental ones. The ideas
      of possible experimental validation of the model are briefly described.

PMID- 30220351
TI  - Corrigendum to 'Unusual antigen presentation offers new insight into HIV vaccine
      design' [Curr Opin Immunol 46 (2017) 75-81].

PMID- 30220353
TI  - Editorial overview: Lymphatic vessels: More than a draining pipeline.

PMID- 30220352
TI  - Editorial overview: Tough targets.

PMID- 30220350
TI  - Detection of subthreshold atrophy in crossed cerebellar degeneration via two
      compartment mathematical modeling of cell density in DWI: A proof of concept
      study.
AB  - Crossed cerebellar diaschisis (CCD) refers to transneuronal degeneration of the
      corticopontocerebellar pathway, resulting in atrophy of cerebellum contralateral
      to supratentorial pathology. CCD is traditionally diagnosed on nuclear medicine
      studies. Our aim is to apply a biexponential diffusion model, composed of
      intracellular and extracellular compartments, to the detection of subthreshold
      CCD on DWI, with the calculated fraction of the intracellular compartment as a
      proposed measure of cell density. At a voxel-by-voxel basis, we solve for
      intracellular and extracellular coefficients in each side of the cerebellum and
      compare the distribution of coefficients between each hemisphere. We demonstrate,
      in all six CCD cases, a significantly lower contribution of the intracellular
      compartment to the cerebellar hemisphere contralateral to supratentorial
      pathology (p < 0.01). In a separate, proof-of-concept case of pontine stroke, we
      also demonstrate reduced intracellular coefficients in bilateral cerebellar
      hemispheres, excluding middle cerebellar peduncles (p < 0.01). Our findings are
      consistent with a decreased intracellular fraction, presumably a surrogate for
      reduced cellular density in corticopontocerebellar degeneration, despite normal
      appearing scans. Our approach allows detection of subthreshold structural changes
      and offers the additional advantage of applicability to most clinical cases,
      where only three DWI beta values are available.

PMID- 30220354
TI  - Burnout, compassion fatigue and psychological capital: Findings from a survey of
      nurses delivering palliative care.
AB  - BACKGROUND: Ageing populations worldwide and a concomitant increase in chronic
      conditions translates into an increased demand for the delivery of palliative and
      end of life care by nurses. This increasing demand for palliative care provision
      may produce stressors resulting in negative outcomes such as burnout and
      compassion fatigue. AIM: The purpose of this study was to explore burnout and
      compassion fatigue, as well as potential protective factors, among nurses in New
      Zealand. METHODS: An online survey was conducted with 256 registered nurses
      (between January 2016 and February 2017) recruited through nursing organisations
      and a large tertiary level hospital. Data analysis consisted of descriptive
      statistics, multivariate analysis of variance, Pearson correlations, and
      hierarchical multiple regression. RESULTS: Psychological empowerment and the
      commitment and challenge components of psychological hardiness significantly
      predicted lower scores for the burnout while previous palliative care education
      and challenge predicted lower scores for the secondary traumatic stress component
      of compassion fatigue. Significant predictors of compassion satisfaction included
      previous palliative care education, psychological empowerment and both the
      commitment and challenge components of psychological hardiness. CONCLUSION:
      Nurses draw upon unique combinations of "psychological capital" to deal with
      caring for patients with life-limiting illnesses. Any interventions to increase
      nurse palliative care education uptake must be tailored to develop and support
      these internal resources.

PMID- 30220355
TI  - Self-care model based on the theory of unpleasant symptoms in patients with heart
      failure.
AB  - AIMS: This study aimed to test and develop the self-care model based on the
      theory of unpleasant symptoms in patients with HF. BACKGROUND: Although self-care
      may reduce unpleasant symptoms of heart failure (HF), reported rates of effective
      self-care in HF patients are very low. Modifiable factors, including disease
      severity, anxiety, depression, social support, unpleasant symptoms, and self
      efficacy are considered to influence self-care, but little is known about their
      overall impact on self-care. METHODS: A model-testing design was used. Covariance
      structure analysis using the maximum likelihood method was used to evaluate the
      hypothetical model. RESULTS: A total of 209 subjects participated in the study.
      The model-fit indexes of the final model were chi2 = 163.473, Normed chi2 =
      1.796, RMSEA = 0.054, IFI = 0.986, CFI = 0.986, GFI = 0.915, and AGFI = 0.873.
      Disease severity and anxiety had an indirect effect on self-care through
      unpleasant symptoms. Depression and social support had an indirect effect on self
      care through self-efficacy. Lower unpleasant symptoms and higher self-efficacy
      were associated with greater self-care. These predictors explained 61.9% of
      variance in self-care. CONCLUSION: Findings from this study could underscore the
      need to consider nursing strategies that relieve unpleasant symptoms and improve
      self-efficacy to enhance self-care in HF patients.

PMID- 30220356
TI  - Understanding the influence of resilience on psychological outcomes - Comparing
      results from acute care nurses in Canada and Singapore.
AB  - BACKGROUND: Building resilience among nurses is one of the ways to support and
      retain nurses in the profession. Prior literature which evaluated influence of
      resilience on psychological outcomes, were conducted in relatively homogeneous
      populations. It is of interest to evaluate whether relationships between
      resilience and psychological outcomes remain consistent across nations and among
      different nursing populations. AIM: To evaluate a theoretical model of the impact
      of resilience on burnout (BO), secondary traumatic stress (STS) and compassion
      satisfaction (CS) by comparing results between nurses in Canada and Singapore.
      METHOD: A self-reported questionnaire consisting of questions on demographics,
      resilience (Connor-Davidson Resilience Scale), and psychological adjustment
      (Professional Quality of Life) was administered via an online survey. One
      thousand three hundred and thirty-eight nurses working in two Academic Medical
      Centres in Singapore responded to the online survey. Similar data was also
      collected from 329 nurses in Canada. Hypotheses were tested using structural
      equation modeling. RESULTS: Resilience exerts a significant negative direct
      impact on STS, and a significant negative direct impact on BO. Additionally,
      resilience has a positive direct impact on compassion satisfaction. STS exerts a
      positive direct impact on BO while CS has a negative direct impact on BO.
      CONCLUSION: Current study affirmed significant associations between resilience
      and professional quality of life. Knowledge on resilience is key in informing
      design and implementation of resilience-building strategies that include
      professional development, and strengthening of interpersonal skills. A resilience
      based approach will help reduce nurses' BO and STS while caring for their
      patients, and in turn reduce turnover.

PMID- 30220357
TI  - Inpatient fall prevention from the patient's perspective: A qualitative study.
AB  - AIM: The aim of this study was to describe the patient's perspective of fall
      prevention in an acute care setting to aid in the design of patient centered
      strategies. BACKGROUND: Falls are one of the most common adverse events in
      hospitals and can lead to preventable patient harm, increased length of stay, and
      increased healthcare costs. There is a need to understand fall risk and
      prevention from the patients' perspectives; however, research in this area is
      limited. METHODS: To understand the patient perspective, semi-structured
      interviews were conducted with twelve patients at an academic healthcare center.
      RESULTS: Qualitative analysis revealed three major themes: (1) how I see myself,
      (2) how I see the interventions; and (3) how I see us. The theme "How I see
      myself" describes patients' beliefs of their own fall risk and includes the sub
      themes of awareness, acceptance/rejection, implications, emotions, and personal
      plan. Interventions, such as fall alarms, are illustrated in the theme "How I see
      the interventions" and includes the subthemes what I see and hear and usefulness
      of equipment. Finally, "How I see us" describes barriers to participating in the
      fall prevention plan. CONCLUSIONS: Most fall prevention programs favor clinician
      led plan development and implementation. Patient fall assessments needs to shift
      from being clinician-centric to patient-centric. Nurses must develop
      relationships with patients to facilitate understanding of their needs.
      Developing these truly patient-centered programs may reduce the over-reliance on
      bed alarms and allow for implementation of strategies aimed to mitigate
      modifiable risk factors leading to falls.

PMID- 30220358
TI  - A retrospective review of patient outcomes in the pediatric HEROES weight
      management program.
AB  - Pediatric obesity is a public health concern in the U.S. The purpose of this
      study was to describe the impact of a pediatric stage 3 and 4 weight management
      program. Program aims measured: change in biometric values using BMI z-scores;
      intervention attrition rate; and health-related quality of life (HRQOL) from
      admission through the initial six months of the program. The program evaluation
      included a retrospective review of 884 electronic records. Of the 698 children
      that met the inclusion criteria, 468 completed at least one follow-up visit
      within the baseline to 6 month time period. Overall 66.38% of the 468 maintained
      program involvement at the 6 month evaluation. Of the 468 who completed the 6
      months, 192 children/families participated in the clinic only program and 276
      participated both in the clinic and a 12 week contract education/fitness and
      exercise intervention. The completion rate for the contract intervention was
      7.3%. All children demonstrated a decrease in BMI z-scores. There were no
      statistically significant differences (p = 0.276) in the BMI z-change scores from
      baseline to 6 months in the clinic only program; those who did not complete the
      education/fitness and exercise intervention, and those who completed the
      education/fitness and exercise intervention. Children demonstrated a
      statistically significant improvement in their overall HRQOL scale score (p =
      0.001) from baseline to the 6 month evaluation. The results indicate the impact
      of attrition and HRQOL in weight management programs. Further research is needed
      to develop and strengthen the effectiveness of weight management interventions.

PMID- 30220359
TI  - Do patients' demographic characteristics affect their perceptions of self-care
      actions to find safe and decent care?
AB  - AIM(S): This exploratory study examined the relationship of five patient
      demographic characteristics (residence in an urban or rural site, gender, age
      group, marital status, and education level) with the patients' (1) perceived
      importance of, (2) desire to, (3) ability to perform four patient engagement self
      care actions that result in finding safe and decent care. BACKGROUND: Equitable
      access to health care is essential in a humanized health care system. Healthcare
      providers must engage patients in discussions about their desires for their care
      to create person-centered care plans reflecting patient values and wishes.
      METHODS: This secondary data analysis from a cross-sectional survey project
      surveyed community-dwelling adults living in the southern United States, 2015
      2016. This paper only includes responses of participants aged 65 years and older
      (N = 123). Data collected in The Patient Action Inventory for Self-Care and
      demographic questions were used. Chi-square tests and multiple logistic
      regression analyses were used. RESULTS: As revealed in the Chi-square and
      logistic regression findings, self-care actions of "finding a doctor or
      practitioner who meets your needs," "using available information to choose a
      doctor or practitioner," and "using data to choose a hospital or clinic" showed
      some associations with whether seniors resided in an urban or rural community,
      age group, and marital status (P < 0.05). No significant associations between
      these four self-care actions with gender or education were found. CONCLUSIONS: A
      community-based solution is warranted to leverage between patient demographic
      characteristics and their perceived self-care actions by harnessing local factors
      in collaboration with identified patient needs.

PMID- 30220360
TI  - "It's just more personal": Using multiple methods of qualitative data collection
      to facilitate participation in research focusing on sensitive subjects.
AB  - BACKGROUND: Often researchers use only one interview method within a single
      study. However, it is increasingly common for a variety of interview methods to
      be employed within a project. Providing choice to participants may facilitate
      recruitment, particularly when research focuses on a sensitive subject. AIM: This
      paper aims to explore participants' reasons for their choice of interview method
      in qualitative research focusing on a sensitive subject. METHODS: Qualitative
      data was collected from 12 participants regarding their choice of interview
      method (face-to-face, Skype, telephone or email) in a wider study investigating
      parents' experiences following their child's burn-injury. Interview data was
      transcribed verbatim and thematic analysis was used to analyse responses.
      RESULTS: Participants most frequently chose to take part in an interview by
      telephone (n = 5), followed by email (n = 4), then Skype (n = 2), and face-to
      face (n = 1). Four themes emerged suggesting that participants' decisions to
      participate via a particular method were determined by personal convenience,
      their belief in their ability to be open with the researcher despite potential
      upset caused by the topic, their ability to get a "feel" for the researcher, and
      concern about giving adequate depth in responses. CONCLUSIONS: Flexibility
      regarding the ways in which participants can take part in qualitative research
      may improve participant access to research, recruitment, and response-rate.
      Although, the depth and quantity of data gathered using different methods can
      vary. It is important that researchers consider the procedures and
      appropriateness of using different methods of interviewing and what impact such
      methods might have upon themselves and their participants.

PMID- 30220361
TI  - Estimating the association between burnout and electronic health record-related
      stress among advanced practice registered nurses.
AB  - BACKGROUND: Health information technology (HIT), such as electronic health
      records (EHRs), is a growing part of the clinical landscape. Recent studies among
      physicians suggest that HIT is associated with a higher prevalence of burnout.
      Few studies have investigated the workflow and practice-level predictors of
      burnout among advanced practice registered nurses (APRNs). AIM: Characterize HIT
      use and measure associations between EHR-related stress and burnout among APRNs.
      METHODS: An electronic survey was administered to all APRNs licensed in Rhode
      Island, United States (N = 1197) in May-June 2017. The dependent variable was
      burnout, measured with the validated Mini z burnout survey. The main independent
      variables were three EHR-related stress measures: time spent on the EHR at home,
      daily frustration with the EHR, and time for documentation. Logistic regression
      was used to measure the association between EHR-related stress and burnout before
      and after adjusting for demographics, practice-level characteristics, and the
      other EHR-related stress measures. RESULTS: Of the 371 participants, 73 (19.8%)
      reported at least one symptom of burnout. Among participants with an EHR (N =
      333), 165 (50.3%) agreed or strongly agreed that the EHR added to their daily
      frustration and 97 (32.8%) reported an insufficient amount of time for
      documentation. After adjustment, insufficient time for documentation (AOR = 3.72
      (1.78-7.80)) and the EHR adding to daily frustration (AOR = 2.17 (1.02-4.65))
      remained predictors of burnout. CONCLUSIONS: Results from the present study
      revealed several EHR-related environmental factors are associated with burnout
      among APRNs. Future studies may explore the impact of addressing these EHR
      related factors to mitigate burnout among this population.

PMID- 30220362
TI  - Healthcare providers' neurobiological response to workplace violence perpetrated
      by consumers: Informing directions for staff well-being.
AB  - AIMS: To examine the neurobiological response experienced by healthcare workers
      when exposed to workplace violence perpetrated by consumers, with a view to
      informing future training and self-care strategies for staff well-being.
      BACKGROUND: Considerable work has been undertaken internationally to identify the
      causes of workplace violence and to develop legislation and guidance for reducing
      the risk in healthcare. However, there is a gap in understanding workers' innate
      neurobiological response to workplace violence, and how to prepare staff to
      recognise the professional and self-care implications of such a response. DESIGN:
      This explanatory study was part of a larger descriptive study. METHODS:
      Individual and group interviews were conducted with managers, directors,
      health/safety staff, nurses and educators (n = 99) from rural and metropolitan
      health services in Australia. Inductive thematic analysis was conducted, followed
      by in depth analysis to answer the question: what neurobiological response could
      be occurring when healthcare workers experience workplace violence? The
      analytical framework was informed by polyvagal theory. RESULTS: With the
      increased risk of threat to physical and personal safety in the workplace,
      healthcare workers may experience activation of the fight, flight or freeze
      response, affecting their wellbeing and performance at work and at home.
      Participants recognised a need to care for themselves and understand their own
      reactions, so that they could better address the needs of consumers. CONCLUSIONS:
      Education for health care workers should include knowledge of the neurobiological
      responses to threat, and techniques to increase their capacity to identify, and
      manage their responses. An understanding of trauma-informed care for staff, will
      enable them to recognise the cumulative effects of workplace violence, and
      identify strategies to manage their well-being. RELEVANCE TO CLINICAL PRACTICE:
      Information about the body's neurobiological response to stressors that threaten
      physiological and psychological safety can assist healthcare providers to better
      understand how to respond to workplace violence and aggression.

PMID- 30220363
TI  - Use of integrative medicine approaches for treating adults with sleep
      disturbances.
AB  - AIM: This study determined the prevalence, perceived efficacy, and influencing
      factors and evaluated the sources of information as well as the barriers and
      facilitators for the use of integrative medicine approaches (IMA) within the
      previous 12 months to treat adults with sleep disturbances. BACKGROUND: No
      studies have assessed the use of integrative medicine approaches in adults with
      sleep disturbances. METHODS: A cross-sectional postal survey was conducted.
      Adults with sleep disturbances were purposively selected from the sleep center of
      a hospital in Taiwan. Binary logistic regression was used to analyze and compare
      the differences between groups of use and non-use IMA. RESULTS: The response rate
      was 94.5% (n = 515). The prevalence for the use of integrative medicine
      approaches was 53.4% (n = 275). The most prevalent IMA was music. However, the
      most perceivably efficacious integrative medicine approaches was acupressure,
      followed by music and meditation. Independent explanatory variables were
      educational attainment, the number of chronic diseases/symptoms, and healthy
      lifestyles for the use of IMA. The most common source of information was
      television/radio. The top facilitator and barrier for the use of integrative
      medicine approaches were side effects of sleeping pills and limited
      accessibility. CONCLUSIONS: IMA are used by a considerable proportion of adults
      for treating sleep disturbances in Taiwan. The findings of this study identified
      the significant explanatory variables of IMA use and provided a fundamental
      understanding the aspects of IMA use in the adults with sleep disturbances is
      particularly important for health care providers in practice associated with
      their patients.

PMID- 30220364
TI  - Compliance of Middle Eastern hospitals with the central line associated
      bloodstream infection prevention guidelines.
AB  - AIMS: The purposes of this study were to (1) assess compliance with the CLABSI
      prevention guidelines, (2) assess the predictors of compliance, and (3)
      investigate the effect of compliance on the rate of CLABSI and related mortality.
      BACKGROUND: Implementation of the Central Line Associated Bloodstream Infection
      (CLABSI) prevention guidelines from the Centers for Disease Control and
      Prevention (CDC) helps to reduce the rate of CLABSI and related mortality,
      although the extent to which hospitals implement these guidelines is
      questionable. METHODS: A prospective design was used in this study. Observations
      were conducted over three months in the intensive care units of 58 hospitals in
      three Middle Eastern countries. An observational checklist, based on the CDC
      guidelines, was used to assess compliance. The rate of CLABSI and related
      mortality were obtained from patients' records. RESULTS: The degree of
      compliance, rate of CLABSI and mortality were highly variable. The multiple
      regression model showed that the hospitals' characteristics explained 82.0% of
      the variance of compliance (R2Adj= 0.820, F=29.82, p<0.05). The number of beds in
      the intensive care unit and patient-nurse ratio were significant predictors of
      compliance. A lower number of beds and a lower patient-to-nurse ratio were
      related to higher compliance. Moreover, higher compliance with CLABSI prevention
      guidelines was associated with lower rate of CLABSI and related mortality.
      CONCLUSIONS: Improvement in the patients' outcome can be achieved through
      compliance with the CLABSI prevention guidelines. lowering patient-nurse ratio
      and the number of beds in the ICUs would help to improve compliance.

PMID- 30220365
TI  - Distress and demoralization of hospital nurses as a function of sources of stress
      and job seniority.
AB  - AIM: To explore job-related factors associated with distress and demoralization
      among hospital nurses, using a cross-sectional mixed-method design. BACKGROUND:
      Sources of job stress for nurses are mainly organizational or emotional care
      related and can result in adverse outcomes such as distress or demoralization,
      but factors associated with demoralization in nurses still need to be thoroughly
      explored. METHODS: A convenience sample of 150 nurses from three public hospitals
      completed an online survey on job stress, distress, demoralization, and feelings
      of entrapment in the caring profession. RESULTS: Emotional job stress was linked
      to higher distress and demoralization, compared to no job stress, and to higher
      feelings of entrapment, compared to both organizational and no job stress, among
      senior nurses. CONCLUSIONS: This pilot study points to the study of
      demoralization as a promising line of research in hospital nursing, but further
      longitudinal studies with larger samples are needed.

PMID- 30220366
TI  - Knowledge and feelings about colorectal cancer among the Jewish adult population
      in Israel: A mixed methods study.
AB  - BACKGROUND: Few previous studies found that people's knowledge of colorectal
      cancer (CRC) risk factors and symptoms is a predictor of high compliance with CRC
      screening. Feelings about CRC have rarely been examined. AIM: This mixed method
      study is aimed at examining knowledge and feelings about CRC among the Jewish
      adult population in Israel. METHODS: One hundred and ninety six Jewish Israelis
      were interviewed using semi-structured face to face personal interviews. Clinical
      characteristics and knowledge about CRC were analyzed by quantitative methods.
      Feelings about CRC were analyzed by the qualitative constant comparative method.
      RESULTS: Most of the participants were at risk for developing CRC due to their
      native background as Jews of Eastern European origin. The most well known risk
      factor was family history of CRC, but only a third were aware of it. Screening
      for CRC by colonoscopy was known to about half the participants. CRC evoked
      negative feelings of fear of contracting an oncological disease, stress as a
      result of a new realty, sadness at the possibility of late discovery, disgust and
      embarrassment because of the involvement of an intimate area and the connection
      to body secretions. Positive feelings of optimistic faith and hope were found
      with regard to survival. CONCLUSION: The knowledge level of the participants
      about CRC symptoms, risk factors, and recommended screening was low to moderate.
      CRC evoked mainly negative feelings. Increasing knowledge about CRC and reducing
      negative feelings evoked by CRC are essential.

PMID- 30220367
TI  - Differences in religiosity among cognitively intact, mildly cognitively impaired,
      and mildly demented elderly, and its possible relationship with depressive mood.
AB  - INTRODUCTION: According to literature, religious attitudes can enhance cognitive
      functioning in elders, because it gives the sense of purpose in life. Therefore,
      due to the controversy among studies, it is of great importance to identify
      whether religiosity levels are greater in cognitively intact elders compared to
      participants with MCI as well as in patients with mild dementia irrespective
      etiology. OBJECTIVE: This study aims to examine possible differences with regards
      to religiosity levels between controls, MCI and patients with mild dementia.
      METHODOLOGY: Religiosity was measured using the Systems of Belief Inventory (SBI
      15R, Holland, et al., 1998), which was standardized in Greek population. RESULTS:
      According to the ANOVA test, significant main effect was found for group by means
      of SBI-15R score F(2, 400) = 5.624, p = .004, eta2 = .027. Post-hoc comparisons
      showed that MCI participants had significantly higher total religiosity scores (M
      = 35.48, SD = 9.67) compared to the healthy controls (M = 31.73, SD = 4.11), p =
      .002. Additionally, patients with mild dementia had also increased religiosity
      scores (M = 35.13, SD = 9.09) compared to controls (M = 31.73, SD = 4.11), p =
      .010. Additionally, Pearson correlation showed significant relationship between
      GDS with SBI-15R score (r = -.221 p = .023) and Religious beliefs & practices
      subscale (r = -.260 p = .007) in patients with mild dementia. CONCLUSION: Results
      suggested that MCI participants as well as patients with mild dementia
      demonstrated higher religiosity levels compared to the healthy controls.
      Moreover, the total religiosity levels were related with depressive
      symptomatology only in patients with mild dementia unlike to the other two
      groups.

PMID- 30220368
TI  - Adherence to home-based inspiratory muscle training in individuals with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an incurable
      progressive illness characterized by airflow limitation and respiratory failure.
      Inspiratory muscle training (IMT) combined with pulmonary rehabilitation
      increases inspiratory muscle strength and endurance, and it decreases dyspnoea.
      Little is known about IMT adherence, and in the present study, we aimed to
      evaluate adherence to home-based IMT used with automatic internet-based feedback,
      in patients with chronic obstructive pulmonary disease. METHOD: The adherence was
      evaluated at an individual level by completing a before-and-after comparison
      between two groups. Over a 12-week study period, the participants performed two
      daily sessions of 30 breaths with a mechanical threshold loading training device.
      They were randomly assigned to either a group of people who self-reported their
      perceived exertion during breathing and who received automatic internet-based
      feedback regarding their next threshold loadings, or a group of people who
      performed IMT with 30% maximal inspiratory pressure and who received no feedback.
      RESULTS: The group of patients who self-reported their perceived exertion showed
      significantly better training adherence compared with the group of patients who
      received no feedback. CONCLUSION: Adherence was greater among patients who self
      reported their perceived breathing exertion and received automatic internet-based
      feedback on the next threshold loadings compared with patients who self-reported
      training sessions without feedback.

PMID- 30220369
TI  - Prevalence of depression and anxiety in end-stage renal disease: A survey of
      patients undergoing hemodialysis.
AB  - BACKGROUND: Dialysis is a lifelong treatment required by end stage renal disease
      patients who are not able to undergo renal transplantation. Dialysis impacts the
      patients' quality of life drastically, increasing the risk of mortality.
      Depression and anxiety are commonly reported among dialysis patients, but their
      prevalence and correlates vary by sociocultural context. OBJECTIVE: The aim of
      this study is to examine the prevalence of anxiety and depression and associated
      factors among patients receiving hemodialysis at a major tertiary referral
      medical center in Lebanon that receives patients from all over the country.
      DESIGN: A cross-sectional, descriptive design was used. METHODS: Ninety patients
      receiving hemodialysis were targeted using convenience sampling, with a final
      sample size of 83 patients. The patients were interviewed while undergoing their
      dialysis session using the Hospital Anxiety and Depression Scale, and asked
      demographic and clinical questions. RESULTS: The majority of participants were
      married men over 60 years of age; 48% achieved high school education. Depression
      was prevalent in 40.8% and anxiety in 39.6%, with 20 patients (24.1%) having both
      conditions. Although 24.1% self-reported anxiety symptoms, only 2.4% were taking
      anxiolytics. Illiterate patients had significantly higher depression scores than
      those with higher levels of education (p = 0.021). Patients who were living with
      their family had higher anxiety scores than those living alone (p = 0.014).
      CONCLUSION: Anxiety and depression are underdiagnosed and undertreated in
      Lebanese dialysis patients. Screening and appropriate referral to mental health
      specialists are needed.

PMID- 30220370
TI  - Association between good work ability and health behaviours among unemployed: A
      cross-sectional survey.
AB  - BACKGROUND: There has been relatively little research on the possible factors
      promoting good work ability among unemployed people. Consequently, the role of
      health behaviours in good work ability among the unemployed is unknown. PURPOSE:
      To explore the work ability and health behaviours of unemployed people through
      sociodemographic factors and examine the association between good work ability
      and health behaviours. DESIGN: A cross-sectional survey. METHODS: The study is
      based on the Finnish nationwide Regional Health and Well-being Study using mailed
      and online questionnaires in 2014-2015. A total of 1973 unemployed or laid-off
      people between the ages of 20 and 65 responded to the survey. The associations of
      work ability with sociodemographic factors - gender, age, marital status, minors
      (i.e. under-18s) living in the household, education, living environment, and
      duration of unemployment - and health behaviours with sociodemographic factors
      were first explored using cross-tabulations. Health behaviours included body mass
      index, daily smoking, alcohol consumption, vegetable consumption, health
      promotion groups, physical exercise, and sitting in one's leisure time. Health
      behaviours were then examined using logistic regression analyses, in association
      with good work ability; the latter was measured with the Work Ability Score.
      RESULTS: Being aged below 45, being married or cohabiting, having a high level of
      education, and short-term unemployment were associated with good work ability. A
      quarter of participants were daily smokers. A proportion of women with risk level
      alcohol use (79%) was higher than that of men (59.9%). A third of unemployed
      people participated in high-intensity physical activity. In regression analyses,
      high-intensity physical activity (OR 2.25, 95% CI 1.06-4.78) was associated with
      good work ability. CONCLUSIONS: Unemployed women and men widely exhibited
      unhealthy behaviours such as daily smoking and a risk level use of alcohol.
      Health promotion actions for enhancing a healthy lifestyle and good work ability
      among unemployed people, particularly in emphasizing the importance of physical
      activity, are highly recommended.

PMID- 30220371
TI  - An examination of the correlation between nurses' organizational trust and
      burnout levels.
AB  - INTRODUCTION: Decrease in the organizational trust level of nurses, leads to
      increase turnover rate of nurses, causes an increase in workload, causes a
      decrease in motivation and quality of patient care. The results caused by the
      lack of organizational trust is important for both individuals and organizations.
      AIM: To investigate the relationship between nurses' organizational trust and
      burnout level. METHOD: This descriptive and relational study is carried out at an
      university hospital with 155 nurses who were agreed to participate. Data were
      collected with Identifying Information Form, Organizational Trust Inventory and
      Maslach Burnout Inventory. Data were analyzed with numbers, percentage, mean
      standard deviation, spearman correlation analysis and multiple linear regression.
      FINDINGS: A negative, very weak and statistically significant relationship was
      found between emotional exhaustion level and trust in employer level (r = 0.304,
      p < 0.01) and trust in institution level (r = 0.335, p < 0.01); a negative, very
      weak and statistically significant relationship was found between emotional
      exhaustion level and trust in colleagues level (r = 0.240, p < 0.01); between
      depersonalization level and trust in employer level (r = 0.315, p < 0.01);
      between depersonalization level and trust in colleagues level (r = 0.282, p <
      0.01); between reduced personal accomplishment level and trust in employer level
      (r = 0.238, p < 0.01). RESULTS: It was concluded that there was a statistically
      significant relationship between the nurses' organizational trust level and
      burnout level. In addition, organizational trust was a significant predictor of
      emotional exhaustion, depersonalization and reduced personal accomplishment
      level.

PMID- 30220372
TI  - Development of the Perspectives on Caring for Older Patients scale: Psychometric
      analyses.
AB  - AIM: The purpose of these studies was to determine the reliability and validity
      of the 24 item Perspectives on Caring for Older Patients (PCOP) scale and further
      develop the scale as a useful tool for measuring nurses' perspectives toward
      caring for older patients. BACKGROUND: Ageism has long been an issue in the U.S.
      as well as globally and is reflected in the attitudes of nurses caring for older
      patients. Most research in this area utilizes scales that measure attitudes
      toward older adults or aging in general which is different from how nurses feel
      about caring for older patients. METHODS: Instrument development studies using
      the PCOP scale were conducted involving two independent samples for exploratory
      and confirmatory analyses. Study 1 included nurses and nursing students from six
      hospitals in the U.S. while Study 2 included students in a baccalaureate nursing
      program. Exploratory factor analysis was conducted in Study 1, and confirmatory
      factor analysis using structural equation modeling was performed in Study 2. A
      test of structural invariance was used to confirm stability of factor structure
      across samples. RESULTS: Exploratory factor analysis using split samples (Study
      1) resulted in a PCOP scale with 12 items, and structural equation modeling
      confirmed a 9-item factor structure. The test for invariance also showed an
      excellent fit to the data. CONCLUSIONS: The revised nine-item PCOP scale is a
      reliable and valid tool for use in measuring nurses' perspectives toward caring
      for older patients in the U.S. and internationally.

PMID- 30220374
TI  - Immunizations - Nursing Interventions to Enhance Vaccination Rates.

PMID- 30220375
TI  - Parents' Perspectives on Their Child's Social Experience in the Context of
      Childhood Chronic Illness: A Qualitative Study.
AB  - PURPOSE: Many children suffer from a serious chronic illness. These children have
      greater risks of developing psychosocial difficulties, associated with school
      absenteeism and missed social opportunities. Through parents' perspectives, this
      study aimed to gain a holistic understanding of children's social experience in
      the context of chronic illness. DESIGN AND METHODS: We conducted semi-structured
      interviews with parents of a child with a serious chronic illness exploring their
      child's school experience. Two researchers coded social experiences using an
      iterative process, involving regular team discussions. Theoretical thematic
      analysis and content analysis were both performed, using the social ecological
      model as a theoretical framework. RESULTS: Forty-nine parents participated (43
      mothers, 6 fathers; child mean age 11.51 years; 21 female children, 28 male
      children; 6 different chronic illness groups). According to parents, the main
      facilitators to the social experience of their children involved parents
      themselves, the school, social networks and peers, as they were all able to
      provide social support and opportunities for social development. However, peers
      were also a source of bullying and peer pressure, and sometimes lacked
      understanding and empathy. CONCLUSIONS: As shown by the social ecological model,
      social functioning between chronically-ill children and their peers can be
      influenced by many factors. More specifically, parents have expressed their
      ability for promoting positive experiences between their children and their
      peers. Practice Implications Considering the complexity of social functioning,
      future research and interventions should provide holistic support for children
      with chronic illnesses.

PMID- 30220376
TI  - Outcomes of anticoagulated patients with atrial fibrillation treated with or
      without antiplatelet therapy - A pooled analysis from the PREFER in AF and PREFER
      in AF PROLONGATON registries.
AB  - BACKGROUND: Evidence on whether antiPLT added to OACs is of advantage in atrial
      fibrillation (AF) patients with concomitant stable coronary artery disease (CAD)
      is limited. We evaluated clinical outcomes with oral anticoagulant (OAC)
      monotherapy vs antiplatelet therapy (antiPLT) plus OAC in patients with AF and
      stable CAD. METHODS: Data on 1058 AF patients on OACs and history (>1 year) of
      myocardial infarction or coronary stenting were pooled from the PREFER-in-AF and
      PREFER-in-AF PROLONGATION registries. We primarily compared the 1-year incidence
      of a net composite endpoint (primary endpoint), including acute coronary syndrome
      and major bleeding, with or without antiPLT. RESULTS: The incidence of the
      primary net composite endpoint was significantly higher in patients receiving
      OACs + antiPLT (N = 348) vs OACs alone (N = 710): 7.9 vs 4.2 per 100
      patients/year; adjusted OR [95% CI] 1.84 [1.01-3.37]; p = 0.048. Among the
      components of the primary endpoint, the greatest relative difference was found
      for major bleeding (OR [95% CI] 2.28 [95% CI 1.00-5.19]), and especially life
      threatening or non-gastrointestinal bleeding. The net clinical outcome with OACs
      + antiPLT was poorer irrespective of the type of CAD (previous infarction or
      coronary stenting), the type of stent (bare metal or drug-eluting) or the type of
      OAC (vitamin K antagonist or non-vitamin K antagonist OAC). CONCLUSIONS: Among
      patients with AF and stable CAD >1-year after the index event, the addition of
      antiPLT to OAC does not apparently provide added protection against coronary
      events, but increases major bleeding. OAC monotherapy should thus be considered
      the antithrombotic therapy of choice for such patients.

PMID- 30220377
TI  - Simvastatin reduces TGF-beta1-induced SMAD2/3-dependent human ventricular
      fibroblasts differentiation: Role of protein phosphatase activation.
AB  - BACKGROUND: Excessive cardiac fibrosis due to maladaptive remodeling leads to
      progression of cardiac dysfunction and is modulated by TGF-beta1-activated
      intracellular phospho-SMAD signaling effectors and transcription regulators.
      SMAD2/3 phosphorylation, regulated by protein-phosphatases, has been studied in
      different cell types, but its role in human ventricular fibroblasts (hVFs) is not
      defined as a target to reduce cytokine-mediated excessive fibrotic response and
      adverse cardiac remodeling. Statins are a class of drugs reported to reduce
      cardiac fibrosis, although underlying mechanisms are not completely understood.
      We aimed to assess whether simvastatin-mediated reduction in TGF-beta1-augmented
      profibrotic response involves reduction in phospho-SMAD2/3 owing to activation of
      protein-phosphatase in hVFs. METHODS AND RESULTS: Cultures of hVFs were used.
      Effect of simvastatin on TGF-beta1-treated hVF proliferation, cytotoxicity,
      myofibroblast differentiation/activation, profibrotic gene expression and protein
      phosphatase activity was assessed. Simvastatin (1 MUM) reduced effect of TGF
      beta1 (5 ng/mL) on hVF proliferation, myofibroblast differentiation (reduced
      alpha-smooth muscle actin [alpha-SMA-expression]) and activation (decreased
      procollagen-peptide release). Simvastatin also reduced TGF-beta1-stimulated time
      dependent increases in SMAD2/3 phosphorylation and nuclear translocation,
      mediated through catalytic activation of protein-phosphatases PPM1A and PP2A,
      which physically interact with SMAD2/3, thereby promoting their
      dephosphorylation. Effect of simvastatin on TGF-beta1-induced fibroblast
      activation was annulled by okadaic acid, an inhibitor of protein-phosphatase.
      CONCLUSIONS: This proof-of-concept study using an in vitro experimental cell
      culture model identifies the protective role of simvastatin against TGF-beta1
      induced hVF transformation into activated myofibroblasts through activation of
      protein phosphatase, a novel target that can be therapeutically modulated to curb
      excessive cardiac fibrosis associated with maladaptive cardiac remodeling.

PMID- 30220378
TI  - The Pythagorean theorem reveals the inherent companion of cardiac ejection
      fraction.
AB  - BACKGROUND: Quantification of ventricular performance requires a comprehensive
      metric which is manageable for patient care and clinical trials. Ejection
      fraction (EF) has been embraced as an attractive candidate. However, being a
      dimensionless ratio, EF has serious limitations. METHODS: We aim to identify what
      information is not recognized when limiting the volume-related analysis by
      exclusively relying on EF. This investigation applies the volume domain concept,
      relating end-systolic volume (ESV) to end-diastolic volume (EDV). This approach
      allows graphical identification of the information not covered by EF.
      Implications for atria, left ventricle (LV) and right ventricle (RV) are
      investigated in healthy individuals, and cardiac patient groups using various
      imaging modalities. RESULTS: The Pythagorean theorem indicates that the
      hypotenuse which relates any {EDV, ESV} combination to EF corresponds with the
      information not covered by the single metric EF. The impact of the recovered EF
      companion (EFC) is illustrated in healthy adults (N = 410, LV 2D
      echocardiography), heart transplant patients (N = 101, LV CT), individuals with
      heart failure (N = 197, biplane angiocardiography), for the RV with corrected
      Fallot (N = 124, MRI), diameters for left atrium (N = 49, MRI) and area for right
      atrium (N = 51, MRI). For any limited EF range we find a spectrum of EFC values,
      showing that the two metrics contain (partly) independent information, and
      emphasizing that the sole use of EF only partially conveys the full information
      available. CONCLUSIONS: The EFC is a neglected companion, containing information
      which is additive to EF. Analysis based on ESV and EDV is preferred over the use
      of EF.

PMID- 30220379
TI  - Cost-effectiveness of rivaroxaban and aspirin compared to aspirin alone in
      patients with stable cardiovascular disease: An Australian perspective.
AB  - OBJECTIVE: In light of the Cardiovascular Outcomes for People using
      Anticoagulation Strategies (COMPASS) trial, our objective was to assess the cost
      effectiveness, from the Australian healthcare perspective, of rivaroxaban in
      combination with aspirin versus aspirin alone for the prevention of recurrent
      cardiovascular disease among patients with stable atherosclerotic vascular
      disease. METHODS: A Markov model was developed using input data from the COMPASS
      trial to predict the clinical course and costs of patients over a 20-year time
      horizon. The model comprised of three health states: 'Alive without recurrent
      CVD', 'Alive after recurrent CVD' and 'Dead'. Costs were from the Australian
      public healthcare system perspective, and estimated from published sources, as
      were utility data. The costs of rivaroxaban were based on current acquisition
      prices on the Australian Pharmaceutical Benefits Schedule (PBS) and assumed as
      AUD$3.09/day. The main outcome of interest was the incremental cost-effectiveness
      ratio (ICER) in terms of cost per quality adjusted life year (QALY) gained, and
      cost per year of life saved (YoLS). Costs and benefits were discounted by 5.0%
      per year. RESULTS: Compared to aspirin alone, rivaroxaban plus aspirin was
      estimated to cost an additional AUD$12,156 (discounted) per person, but lead to
      0.516 YoLS (discounted) and 0.386 QALYs gained (discounted), over 20 years. These
      equated to ICERs of AUD$23,560/YoLS and AUD$31,436/QALY gained. We have assumed a
      threshold of AUD$50,000/QALY gained to signify cost-effectiveness. CONCLUSION:
      Compared to aspirin, rivaroxaban in combination with aspirin is likely to be cost
      effective in preventing recurrent cardiovascular events in patients with stable
      atherosclerotic vascular disease.

PMID- 30220380
TI  - Comment on "Silybum marianum provides cardioprotection and limits adverse
      remodeling post-myocardial infarction by mitigating oxidative stress and reactive
      fibrosis".

PMID- 30220381
TI  - Neural Circuits of Chronic Pain.

PMID- 30220382
TI  - Epidemiology of Mycobacterium bovis and Mycobacterium tuberculosis in animals:
      Transmission dynamics and control challenges of zoonotic TB in Ethiopia.
AB  - Mycobacterium tuberculosis complex is the cause of tuberculosis (TB) in humans
      and other animals. Specifically, Mycobacterium bovis (M. bovis) and Mycobacterium
      tuberculosis (M. tuberculosis) are highly pathogenic mycobacteria that may infect
      different animal species and are the sources of TB in humans. The objective of
      this paper was to review the epidemiology of M. bovis and M. tuberculosis in
      animals. The review also highlighted the transmission dynamics of M. bovis and M.
      tuberculosis in humans and animals and control challenges of zoonotic TB in
      Ethiopia. The literature review focused on scientific peer-reviewed articles from
      studies exclusively conducted in Ethiopia that were published from 1998 to 2017.
      Husbandry system, breed and herd size have significant role in the epidemiology
      of bovine tuberculosis (BTB) in Ethiopia. The information presented reveals that
      different strains of M. bovis are widely distributed in domestic animals
      predominantly in the Ethiopian cattle and the main strain was found to be SB1176.
      In addition, the isolation of M. tuberculosis from domestic animals in different
      settings signifies the circulation of the agent between humans and animals in
      Ethiopia. The life styles of the Ethiopian communities, close contact with
      domestic animals and/or the habit of consuming raw animal products, are suggested
      as the main factors for transmission of M. bovis and M. tuberculosis between
      human and animal which may have impact on the TB control program in human. In
      Ethiopia, a human TB control program has been widely implemented, however, the
      role of animal in the transmission of the causative agent has been neglected
      which could be one of the challenges for an effective control program. This
      warrants the need for incorporating animal TB control programs using "One Health"
      approach for effective TB control for both human and animal.

PMID- 30220383
TI  - Factors influencing antimicrobial prescribing by Dutch companion animal
      veterinarians: A qualitative study.
AB  - Use of antimicrobials selects for antimicrobial resistance, and this poses a
      threat for both human and animal health. Although previous studies show that
      total antimicrobial use in Dutch companion animal clinics is relatively low and
      decreasing, the majority of antimicrobials prescribed are categorised as
      critically important for human medicine by the World Health Organization (WHO).
      Large differences in use between clinics are also observed. Identification of
      factors that influence the prescribing behaviour of veterinarians is needed to
      tailor future interventions aimed at promoting prudent use of antimicrobials in
      companion animals. The aim of this study was to explore factors influencing the
      antimicrobial prescribing behaviour of companion animal veterinarians in the
      Netherlands. Face-to-face, semi-structured interviews were used to interview 18
      Dutch companion animal veterinarians. Interviews were held until theoretical data
      saturation was reached. An interview guide was used to structure the interviews,
      and ATLAS.ti 7.5 was used to manage and analyse the qualitative data. An
      iterative approach was applied to develop a conceptual model of factors that
      influence antimicrobial prescribing behaviour. The conceptual model shows four
      major categories of factors that influence the antimicrobial prescribing
      behaviour: veterinarian-related factors, patient-related (i.e. owner- and pet
      related) factors, treatment-related factors (i.e. alternative treatment options
      and antimicrobial-related factors) and contextual factors (i.e. professional
      interactions, further diagnostics and environmental factors). All four major
      categories of influencing factors should be addressed to improve awareness on
      antimicrobial prescribing behaviour and to develop an antimicrobial stewardship
      programme for companion animal clinics.

PMID- 30220384
TI  - Pododermatitis in group housed rabbit does in Switzerland-Prevalence, severity
      and risk factors.
AB  - In rabbits (Oryctolagus cuniculus L.), pododermatitis is a chronic multifactorial
      skin disease that appears mainly on the plantar surface of the hind legs. In
      later stages, it causes pain leading to poor welfare of affected animals.
      Pododermatitis is commonly observed in commercial rabbit production in breeding
      does housed with wire mesh flooring. However, the prevalence in breeding does
      that are housed in groups on litter and plastic slats is not known. The aim of
      this cross-sectional study was to investigate the frequency, the severity and
      possible risk factors of pododermatitis in group housed breeding does in
      Switzerland on litter and plastic slats. Between June and September 2016 about
      30% of all adult female breeding rabbits (1090 animals in total) were evaluated
      for the presence and the severity of pododermatitis on 17 commercial rabbit farms
      with group housing. The latter was done with a tagged visual-analogue-scale.
      Additionally, various animal-related (e.g. hybrid, age or body weight) and
      environmental risk factors (e.g. temperature, relative humidity or wet area per
      pen) known from the literature were recorded. The risk factors were analysed with
      generalized linear models, additive Bayesian network (ABN) models resulting in
      directed acyclic graphs (DAGs) and random forests with variable importance plots.
      On average, 25% of the rabbits displayed ulcerative pododermatitis likely to be
      painful on at least one hind leg, while the prevalence varied between farms from
      4 to 49%. The age, body weight and claw-length of the animals were positively
      associated with pododermatitis as the most important risk factors. The best model
      explained 37.4% of the observed variance in the primary outcome measure for
      pododermatitis. These findings demonstrate that pododermatitis is prevalent in
      female breeding does even in group housing systems with litter and plastic slats.
      However, the results of this cross-sectional study also indicate that important
      risk factors may have been missed or were not recorded precisely enough. Thus,
      more in-depth research is needed to assess risk factors of pododermatitis in view
      of effectively preventing the occurrence of this painful disease.

PMID- 30220385
TI  - Tool for predicting Caligus rogercresseyi abundance on salt water salmon farms in
      Chile.
AB  - Caligus rogercresseyi is a host-dependent parasite that affects rainbow trout and
      Atlantic salmon in Chile. Numbers of sea lice on fish increase over time at
      relatively predictable rates when the environment is conducive to the parasite's
      survival and fish are not undergoing treatment. We developed a tool for the
      salmon industry in Chile that predicts the abundance of adult sea lice over time
      on farms that are relatively isolated. We used data on sea louse abundance
      collected through the SalmonChile INTESAL sea lice monitoring program to create
      series of weekly lice counts between lice treatment events on isolated farms. We
      defined isolated farms as those with no known neighbors within a 10 km seaway
      distance and no more than two neighbors within a 20 km seaway distance. We
      defined the time between sea lice treatments as starting the week immediately
      post treatment and ending the week before a subsequent treatment. Our final
      dataset of isolated farms consisted of 65 series from 32 farms, between 2009 and
      2015. Given an observed abundance at time t = 0, we built a model that predicted
      8 consecutive weekly sea louse abundance levels, based on the preceding week's
      lice prediction. We calibrated the parameters in our model on a randomly selected
      subset of training data, choosing the parameter combinations that minimized the
      absolute difference between the predicted and observed sea louse abundance
      values. We validated the parameters on the remaining, unseen, subset of data. We
      encoded our model and made it available as a Web-accessible applet for producers.
      We determined a threshold, based on the upper 97.5% predictive interval, as a
      guideline for producers using the tool. We hypothesize that if farms exceed this
      threshold, especially if the sea lice levels are above this threshold 2 and 4
      weeks into the model predictions, the sea louse population on the farm is likely
      influenced by sources other than lice within the farm.

PMID- 30220386
TI  - Using social network analysis to characterize the collaboration network of
      backyard poultry trainers in ackCalifornia.
AB  - In order to better understand collaboration among trainers in the backyard
      poultry community (i.e. feed store managers, youth development programs (i.e. 4
      H), veterinarians, government agencies, extension resources and backyard poultry
      club leaders), Social Network Analysis (SNA) was used as a tool to better
      characterize and quantify the current collaboration network structure of backyard
      poultry trainers in California. Invited trainer attendees of two "Train-the
      Trainers" poultry workshops (n = 67) held in Northern and Southern California
      were given a survey that asked them to list contacts that they collaborated with
      on backyard poultry (BYP) related work. The collaboration network in this study
      included a total of 109 trainers, 18 practitioners, and 32 individuals who are
      both trainers and practitioners for a total of 170 nodes (11 individuals did not
      have affiliation information available). In order to help identify central actors
      or collaboration leaders, the surveys were analyzed using Social Network Analysis
      (SNA), which allows for a quantitative analysis of relationships among various
      stakeholders. While the SNA showed that the existing collaboration network is
      disconnected with a clustering coefficient of 0.043 and median total degree
      centrality of 1 (range 9) and therefore not conducive for collaboration, key
      insights that could help restructure and improve the network were identified. As
      an example, among different poultry groups, 4-H was identified as the
      organization with the second highest median coverage score and fifth highest
      median centrality score. In addition, 4-H group leaders act as both trainers and
      practitioners. Consequently, outreach to 4-H group leaders throughout the state
      would potentially have the greatest impact with respect to overall coverage both
      inside and outside the 4-H network due to their high centrality and boundary
      spanning roles. Using SNA to strengthen the collaboration network infrastructure
      of backyard poultry trainers ultimately offers a more targeted approach toward
      extension for backyard poultry owners, which could ultimately facilitate
      communication and knowledge-sharing with BYP owners during a disease outbreak.

PMID- 30220387
TI  - Assessment of abattoir based monitoring of PRRSV using oral fluids.
AB  - Various porcine reproductive and respiratory syndrome virus (PRRSV) regional
      elimination projects have been implemented in the U.S., but none have yet
      succeeded. In part, this reflects the need for efficient methods to monitor over
      time the progress of PRRSV status of participating herds. This study assessed the
      feasibility of monitoring PRRSV using oral fluids collected at the abattoir. A
      total of 36 pig lots were included in the study. On-farm oral fluid (n = 10) and
      serum (n = 10) collected within two days of shipment to the abattoir were used to
      establish the reference PRRSV status of the population. Oral fluids (n = 3 per
      lot) were successfully collected from 32 lots (89%) at the lairage. Three
      veterinary diagnostic laboratories (VDLs) tested the sera (VDL1 and VDL3: n =
      316, VDL2: n = 315) and oral fluids (VDL1 and VDL3: n = 319, VDL2: n = 320) for
      PRRSV antibodies (ELISA) and RNA (rRT-PCR). Environmental samples (n = 64, 32
      before and 32 after pigs were placed in lairage) were tested for PRRSV RNA at one
      VDL. All oral fluids (farm and abattoir) tested positive for PRRSV antibody at
      all VDLs. PRRSV positivity frequency on serum ranged from 92.4% to 94.6% among
      VDLs, with an overall agreement of 97.6%. RNA was detected on 1.3% to 1.9%, 8.1%
      to 17.7%, and 8.3% to 17.7% of sera, on-farm and abattoir oral fluids,
      respectively. Between-VDLs rRT-PCR agreement on sera and oral fluids (farm and
      abattoir) ranged from 97.8% to 99.0%, and 79.0% to 81.2%, respectively. Between
      locations agreement of oral fluids varied from 31.3% to 50% depending on the VDL.
      This study reported the application of swine oral fluids collected at the
      abattoir for monitoring PRRSV, and describes the between-VDL agreement for PRRS
      testing of serum and oral fluid field samples.

PMID- 30220388
TI  - Eliciting preferences for attributes of Newcastle disease vaccination programmes
      for village poultry in Ethiopia.
AB  - Newcastle disease (NCD) is an important disease of poultry, directly affecting
      the livelihoods of poor farmers across developing countries. Research has
      identified promising innovations in NCD vaccine development and field trials
      among village poultry have been promising. However, NCD vaccination is not
      currently part of village poultry extension programmes in many developing
      countries. Understanding the preferences for, and relative importance of,
      different attributes of potential vaccination programmes to prevent NCD will be
      crucial in designing acceptable and sustainable prevention programmes. This
      research employed the discrete choice experiment approach to elicit farmers'
      preference for attributes of NCD vaccination programmes for village poultry in
      rural Ethiopia. The choice experiment survey was conducted on 450 smallholder
      farmers. The relative importance of attributes of NCD vaccines to farmers was
      estimated using a random parameter logit regression model. The preferred NCD
      vaccine programme had greater bird-level protection (i.e. greater capacity to
      reduce mortality should NCD occur in a flock), was delivered by animal health
      development agents, and could be administered via drinking water. Results from
      simulations on changes in attribute levels revealed that bird-level protection
      capacity and delivery of vaccine by animal heath extension affect farmers'
      preferences more than other attributes. These findings suggest that it is
      important to ensure NCD vaccine programmes offer reasonable capacity to protect
      against mortality. It also suggests the need to understand farmers' preferred
      vaccine delivery mechanisms and route of vaccine administration for a wider
      acceptance of vaccine.

PMID- 30220390
TI  - Clinical and infection dynamics of foot-and-mouth disease in beef feedlot cattle:
      An expert survey.
AB  - Parameterizing mathematical models of foot-and-mouth disease virus (FMDv)
      transmission is challenging due to knowledge gaps on the variable dynamics in
      susceptible populations. Expert opinion surveys are an approach to gather data on
      topics where no data have been reported. The objective of this study was to
      collect-via an expert-opinion survey-key parameter values of the potential FMD
      natural history and transmissibility in beef feedlot cattle in the U.S. Experts
      with experience working with FMD in endemic and non-endemic settings were
      targeted. Parameters surveyed were: duration of infection and disease stages,
      proportions of animals with specific clinical manifestations, duration and extent
      of the reduction in feed consumption, and probabilities of severe clinical
      disease and FMDv transmission. We surveyed the parameter values for infections by
      strains of different virulence, different infection doses, and routes of
      transmission. Twenty-seven experts from around the world agreed to participate
      and 16 (59%) completed the survey. The expert responses to individual questions
      were resampled via Monte Carlo simulations; to the resulting distributions,
      candidate theoretical distributions were fitted using the maximum likelihood
      method and the sought parameter values estimated based on the best-fit
      distributions. Of the infection stages, the estimates of the expected FMD latent
      period in beef feedlot ranged from 1.7 to 5.3 days and the infectious period from
      5.6 to 10.9 days. Of the disease stages, the estimated incubation period ranged
      from 2.9 to 6.1 days, subclinical period from 1.2 to 2.8 days, and clinical
      period from 4.2 to 7.5 days. Probability of developing clinical disease after
      infection varied from 82% (IQ range 90-70%) with high-virulent to 63% (IQ range
      89-60%) with low-virulent strains. Reduction in feed consumption was estimated to
      last 5 (SD +/- 2) days in cattle infected by a low-virulent FMDv strain and 7 (SD
      +/- 2) days for high virulent strains. The study results can be used in
      combination with experimental and outbreak investigation data to parameterize
      FMDv-transmission models to evaluate intervention responses during hypothetical
      FMD epidemics in beef feedlot populations in the U.S.

PMID- 30220389
TI  - Analysing production and financial data from farmers can serve as a tool for
      identifying opportunities for enhancing extension delivery among the rural
      poultry sub-sector in Zambia.
AB  - There are limited data on production and financial performance of the rural
      poultry sector in developing countries like Zambia that could be used by
      extension services as a feedback loop to enhance service delivery in the sector.
      Thus, a study that used production and financial data obtained from poultry
      farmers of Eastern Zambia was conducted to describe the rural poultry sub-sector
      and conduct financial analysis. It compared the financial performance of
      indigenous chicken production to broiler and layer production. The aim of the
      study was to identify opportunities and knowledge gaps among poultry farmers that
      could be used to initiate and enhance a participatory extension approach and
      build capacity of farmers in the sector. Descriptive, spatial, gross margin and
      breakeven analysis was used to analyse data obtained from 459 rural poultry
      farmers and expert opinion from 5 local extension workers. Poultry ranked highest
      in terms of popularity and numbers when compared with other animals kept by
      respondents (median = 20). Most poultry were kept under free-range and brood an
      average of 3.1 clutches. Except for annual set up costs, some variable costs and
      household poultry consumption, the study could obtain data on most production
      costs and income generated from poultry farmers. Nevertheless, gross margin
      analysis conducted using costing data from poultry farmers and expert opinion of
      extension workers revealed that indigenous chicken enterprises had the highest
      gross margin percentage of 72% compared to commercial broilers and layers which
      had gross margin percentages of 53% and 56% respectively. Breakeven analysis
      revealed that indigenous chickens required the lowest number of products to be
      sold (27) to realise profit compared to broilers (1011) and layers (873). The
      study justifies investment into the rural poultry sub-sector and discusses the
      use of gross margin templates as a means of incentivising rural farmers to
      participate in extension programmes.

PMID- 30220391
TI  - Companion animal demography and population management in Pinhais, Brazil.
AB  - We used a two-stage cluster sampling design to estimate the population sizes of
      owned dogs and cats in Pinhais, Brazil. For dogs, we simulated the population
      dynamics using a compartmental model of coupled differential equations,
      incorporating uncertainties in a global sensitivity analysis and identifying the
      most influential parameters through local sensitivity analysis. The calibration
      with the known human population improved precision in population size for dogs
      but not for cats. Population pyramids had a wide base, and the apparent
      population turnover was lower than the net population gain. Most immigrants came
      from the state capital. Projected dog and human growth rates between 2017 and
      2027 were positive and similar, while the projected proportion of sterilized dogs
      decreased over the same period. The main reason provided for not sterilizing
      animals was the cost of the procedure, even though there were free alternatives.
      The demographic characterization made in the present study will serve for future
      comparisons and as a reference in epidemiological contexts. The simulations
      indicated what to expect in specific scenarios and stressed the need to increase
      current sterilization rates.

PMID- 30220392
TI  - Measuring the success of canine and feline preventative healthcare consultations:
      A systematic review.
AB  - Preventative healthcare consultations account for a large proportion of the
      veterinary caseload. This novel study is the first to methodically review all
      literature on canine and feline preventative healthcare consultations. Previous
      research has found these consultations to be different from health problem
      consultations in terms of communication style and content. Identifying relevant
      evidence and previously validated methods of measuring the success of these
      consultations will be useful when implementing strategies for optimisation. The
      aim of this study was to identify and assess the quality of existing literature
      which describes and/or measures the success of preventative healthcare
      consultations. Database searches of CAB Abstracts and Medline were conducted to
      identify published literature. Google searches were then conducted to identify
      any additional published or grey literature. Results were systematically screened
      to determine whether the returned sources were about cats and/or dogs, whether
      they related to preventative healthcare, and whether they described and/or
      measured the success of preventative healthcare consultations. For primary
      research citations which only described preventative healthcare consultations,
      data were extracted on the aspects of the consultations described. For citations
      which additionally measured the success of the consultations, the measures used,
      sampling technique, key results and key weaknesses were also extracted. Of 17,538
      citations identified in total during the database searches, a total of seven
      relevant primary research citations were identified. All of these citations
      described aspects of the preventative healthcare consultation, such as
      consultation length, health problems discussed, actions taken and communication
      style. Only one primary research citation measured success of the consultation,
      using veterinarian satisfaction to determine success. In addition, 30 narrative
      citations, including expert opinion pieces, textbooks, guidelines without
      transparent methodology and conference presentations were identified. Google
      searches identified 224 relevant narrative citations, and five of the seven
      primary research citations identified by the database searches, but did not
      identify any additional relevant primary research citations. The results suggest
      that, despite accounting for around a third of all consultations, there is
      relatively little evidence describing preventative healthcare consultations and
      only one measure of success has been described for these consultations. This
      presents potential challenges when implementing strategies to optimise these
      consultations, as measures which are useful and relevant to veterinary practice
      should first be identified. Identifying useful measures of success will allow
      future strategies designed to maximise the benefits of these consultations to be
      meaningfully assessed for efficacy.

PMID- 30220393
TI  - Network-based assessment of the vulnerability of Italian regions to bovine
      brucellosis.
AB  - The endemic circulation of bovine brucellosis in cattle herds has a markedly
      negative impact on economy, due to decreased fertility, increased abortion rates,
      reduced milk and meat production. It also poses a direct threat to human health.
      In Italy, despite the long lasting efforts and the considerable economic
      investment, complete eradication of this disease still eludes the southern
      regions, as opposed to the northern regions that are disease-free. Here we
      introduced a novel quantitative network-based approach able to fully exploit the
      highly resolved databases of cattle trade movements and outbreak reports to yield
      estimates of the vulnerability of a cattle market to brucellosis. Tested on the
      affected regions, the introduced vulnerability indicator was shown to be accurate
      in predicting the number of bovine brucellosis outbreaks (Spearman r= 0.82, p=
      0.04), thus confirming the suitability of our tool for epidemic risk assessment.
      We evaluated the dependence of regional vulnerability to brucellosis on a set of
      factors including premises spatial distribution, trading patterns, farming
      practices, herd market value, compliance to outbreak regulations, and exploring
      different epidemiological conditions. Animal trade movements were identified as a
      major route for brucellosis spread between farms (r=0.85,p<10-5 between
      vulnerability and number of inbound movements), with an additional potential risk
      attributed to the use of shared pastures (r=0.4,p=0.04). By comparing the
      vulnerability of disease-free regions in the north to affected regions in the
      south, we found that more intense trade and higher market value of the cattle
      sector in the north (r=0.56,p=0.01) likely inducing more efficient biosafety
      measures, together with poor compliance to trade restrictions following outbreaks
      in the south were key factors explaining the diverse success in eradicating
      brucellosis. Our modeling scheme is both synthetic and effective in gauging
      regional vulnerability to brucellosis persistence. Its general formulation makes
      it adaptable to other diseases and host species, providing a useful tool for
      veterinary epidemiology and policy assessment.

PMID- 30220394
TI  - Epidemiological and ultrasonographic investigation of bovine fascioliasis in
      smallholder production system in Eastern Nile Delta of Egypt.
AB  - Regular updating of our knowledge on the epidemiological determinants of bovine
      fascioliasis is necessary to increase the awareness of the disease's significance
      and subsequently, improve the control measures. The objectives of this study were
      (1) to estimate the prevalence of bovine fascioliasis, and identify the
      association of epidemiological characteristics under traditional householders'
      production systems, (2) to describe the association between the clinical picture,
      Fasciola spp. egg count and hepatobiliary ultrasonography findings. In total, 270
      faecal samples were examined microscopically for the presence or absence of
      Fasciola spp. egg, using the sedimentation-flotation method. Copro-positive
      animals were subjected to ultrasonographic examination. Overall prevalence of
      copro-positive animals was 27.4% (22.4-33.0%, 95% CI). The final multivariate
      analysis showed that there was a significant association between fascioliasis and
      animal species (P < 0.03), and administration of anthelmintic (P < 0.0001).
      Cattle have a less chance of being positive to Fasciola spp. by 0.55 (95% CI:
      0.30 - 0.99) compared to water buffaloes. Administration of anthelmintic to
      animals on a regular basis decreased the risk of copro-positivity to Fasciola spp
      by 0.17 (95% CI: 0.07 - 0.36) compared to animals received anthelmintic on an
      irregular basis. Infected animals having different Fasciola spp. egg burden
      revealed different clinical symptoms associated with hepatobiliary changes on
      ultrasonographic examination ranged from normal hepatic parenchyma and bile
      system in low faecal egg load to hyperechogenic hepatic parenchyma,
      hyperechogenic with distal shadowing bile duct, and distended gallbladder in high
      faecal egg load of Fasciola spp. In conclusion, the prevalence of bovine
      fascioliasis is high under the traditional household's production system. Regular
      administration of anthelmintic significantly reduces the animal's chance of being
      copro-positive to Fasciola spp. Ultrasound poses a valuable prognostic technique
      for assessment of bovine fascioliasis.

PMID- 30220395
TI  - The topology of between-herd cattle contacts in a mixed farming production system
      in western Kenya.
AB  - In many livestock production systems in sub-Saharan Africa, cattle are owned by
      individual keepers but regularly mix with animals from other herds while grazing
      communal land, at watering points or through the use of shared bulls for breeding
      and ploughing. Such contacts may have important implications for disease
      transmission and control but are not well documented. We describe between-farm
      contacts in Kimilili sub-county of Bungoma County, a mixed farming area of
      predominately smallholder farmers. Between-farm contacts occurring during grazing
      or at shared water points over the past four weeks were captured in seven
      randomly selected villages using a photo-elicitation tool. The use of shared
      bulls for breeding and ploughing and cattle introductions from farms within the
      same village in the past 12 months were also captured. Contact networks were
      constructed for each contact type in each village. In total 329 farms were
      included in the study. Networks resembled undirected scale-free graphs with a
      network density ranging between 9.6 and 14.0. Between 45.6 and 100% of the farms
      in each study village had been in contact over the past four weeks through
      grazing and watering contacts. Between 88.9 and 100% were considered to have been
      in contact over the past 12 months. The topology of the networks was
      heterogeneous, with some farms exhibiting a high degree of contact. The degree of
      farm contact and distances between farms were negatively correlated (Pearson
      correlation coefficient range -0.2 to -0.4). Effective disease control and
      surveillance must take into consideration the frequency and range of contacts
      that occur between farms within a single village. Cattle keepers are highly
      interconnected and pathogens that are transmitted through direct or indirect
      animal contact would be expected to spread rapidly in the study system. However,
      the observed heterogeneity in between-farm contact may present opportunities for
      interventions to be targeted to particular herds to limit infectious disease
      spread.

PMID- 30220396
TI  - Estimating the impact on food and edible materials of changing scrapie control
      measures: The scrapie control model.
AB  - Multiple controls established during the bovine spongiform encephalopathy (BSE)
      epidemic were not solely applied to BSE in cattle, but were implemented for
      scrapie in sheep and goats due to concerns over the occurrence of BSE in sheep.
      In the absence of BSE in sheep being observed, control measures for prion
      diseases are now being evaluated to ensure they remain proportionate to risk.
      This risk assessment, aims to estimate, by use of stochastic simulation, the
      impact of reducing controls for Specified Risk Materials (SRM) from sheep at
      abattoir. Three scenarios have been included: 1) current list of SRM; 2) brain
      and spinal cord of adult sheep; and 3) the brain of adult sheep. Results indicate
      the total amount of infectivity passing through British abattoirs is highest for
      atypical scrapie with nearly 3,500,000 Ovine Oral (OO) ID50 per year. The
      majority of this infectivity enters Category 1 waste for incineration, with only
      13,000 OO ID50 per year within edible products. Under Scenario 2, an additional
      4000 OO ID50 per year would be classified as edible products from the lifting of
      restrictions on the distal ileum of adult sheep. However, if SRM removal was
      limited to brain, an additional 110,000 OO ID50 per year would be permitted into
      edible products with the lifting of restrictions on the spinal cord of adult
      sheep. For classical scrapie, there is a mean estimate of infectivity of 30,000
      OO ID50 per year at abattoir. This is lower than for atypical scrapie due to the
      lower occurrence of this disease in Great Britain. However, more infectivity is
      destined to reach the food chain as the disease is peripherally distributed in
      the carcase. The highest contributor to the total amount of infectivity consumed
      per year is the intestines (duodenum and jejunum). If SRM removal is limited to
      the brain and spinal cord of sheep over 12 months of age, there is an approximate
      mean increase from 19,000 to 21,000 OO ID50 per year diverted to edible products.
      If the SRM list is restricted to brain only, this increases to over 23,000 OO
      ID50 per year. For the potential of sheep-BSE, there is a very low estimate of 29
      OO ID50 per year in total from carcases entering abattoir, due to the potential
      very rare occurrence of this disease. Given changes in SRM regulations there is a
      change of an additional 4 OO ID50 per year being diverted to edible products.

PMID- 30220397
TI  - The epidemiology of dog rabies in Algeria: Retrospective national study of dog
      rabies cases, determination of vaccination coverage and immune response
      evaluation of three commercial used vaccines.
AB  - Rabies is a neglected zoonotic disease. Several animal species can transmit
      rabies, but domestic dogs are the main reservoir implicated in rabies
      transmission to human and other susceptible animals. There is a scarcity of data
      regarding canine rabies in Algeria. Hence, this report is the first study that
      attempts to understand the epidemiology of dog rabies through a retrospective
      national study of rabies cases between 2010 and 2016, determination of canine
      vaccination coverage and evaluation of immune response of three rabies commercial
      vaccines used in Algeria. Our results revealed the persistent nature of dog
      rabies in Algeria; with a mean of 131 positive cases per year. The vaccination
      coverage findings indicated that 30.81% (126/409) of the reported vaccinated dog
      and 47.98% (261/544) of all studied dogs presented low level of rabies antibodies
      titres (less than 0.5 IU), and were therefore considered not immune to rabies.
      Additionally, our vaccine evaluation findigs showed a weak immune response of
      inactivated vaccine without adjuvant. Even with adjuvanted inactivated and
      attenuated live vaccines, several vaccinated dogs did not develop vaccine
      protection. Therefore, our results recommend further studies to test the
      efficiency of adding a booster vaccine shot, especially in primo-vaccinated dogs
      to optimize the vaccination protocol; rabies is potentially fatal zoonosis,
      tolerating no vaccine failure. Moreover, the present study establish the
      necessity to re-examine the national rabies control program, implemented in 1996,
      particularly concerning population education, vaccination strategy, surveillance
      and campaigns monitoring.

PMID- 30220398
TI  - Exponential random graph models to evaluate the movement of backyard chickens
      after the avian influenza crisis in 2004-2005, Thailand.
AB  - The aim of this study was to use exponential random graph models (ERGMs) to
      explain networks of movement of backyard chickens in provinces which had been
      hotspots for avian influenza outbreaks in Thailand during 2004-2005. We used
      structured questionnaires to collect data for the period January to December 2009
      from participants who were involved in the backyard chicken farming network in
      three avian influenza hotspots (Ratchaburi, Suphan Buri, and Nakhon Pathom
      provinces) in Thailand. From 557 questionnaires, we identified nodes, points of
      entry and exit from nodes, and activities relating to backyard chicken farming
      and movement of chickens, and generated ERGMs based on non-festive periods (Model
      1) and the Chinese New Year period (Model 2). In Model 1, k-star (the central
      node is connected to k other nodes) connections were predominant (P <  0.001). In
      Model 2, the frequency of movement increased by 10.62 times, k-star connections
      were still predominant (P <  0.001), and the model was scale-free. Hubs were
      formed from owners/observers in the arenas/training fields, farmers who raised
      chickens for consumption only, and traders. In conclusion, our models indicated
      that, if avian influenza was introduced during non-festive periods, the
      authorities would need to regularly restrict the movement of chickens. However,
      during high-frequency periods of movement of backyard chickens, authorities would
      also need to focus on the network hubs. Our research can be used by the relevant
      authorities to improve control measures and reduce the risk or lessen the
      magnitude of disease spread during an avian influenza epidemic.

PMID- 30220399
TI  - Biosecurity practices on foie gras duck farms, Southwest France.
AB  - On-farm biosecurity can be assessed by analyzing patterns of practices to better
      tailor technical advice to producers. Given their close contact with
      environmental and wildlife disease reservoirs, free-range duck farms are exposed
      to multiple risk factors of pathogen exposure that are rare or absent in indoor
      production. The recurrent emergence of Highly Pathogenic Avian Influenza (HPAI)
      viruses in Southeast Asia and Europe has emphasized the importance of farm-level
      biosecurity on free-range duck farms. This study was conducted on 46 French duck
      farms. The farms were visited and an 80-question survey was administered to
      assess biosecurity practices. Patterns of practices were explored with multiple
      correspondence analysis and hierarchical cluster analysis. Farms were assigned to
      one of three clusters in which specific farm types were overrepresented: farms
      specialized in rearing to grow-out phases and open-circuit full cycle (i.e., all
      production phases on the farm) farms in cluster 1, closed-circuit full cycle
      farms in cluster 2, and farms specialized in gavage in cluster 3. Differences in
      practices might be linked with differences in production constraints. This study
      provides a baseline assessment of biosecurity practices on foie gras duck farms
      in Southwest France and will help efforts to adapt biosecurity programs to farm
      types.

PMID- 30220400
TI  - Serological responses of cattle inoculated with inactivated trivalent foot-and
      mouth disease vaccine at the wildlife-livestock interface of the Kruger National
      Park, South Africa.
AB  - Foot-and-mouth disease (FMD) virus is economically one of the world's most
      important animal pathogens, which can be responsible for losses in livestock
      trade, as well as frequent and highly disruptive large-scale epidemics. The
      control of FMD in southern Africa typically includes vaccination of cattle with a
      trivalent or bivalent vaccine preparation. The objective of this study was to
      determine the level and duration of the antibody responses conferred by the
      current FMD vaccination programme in cattle at the western boundary of the Kruger
      National Park (KNP) in South Africa. Two hundred and eighty-three cattle from
      four communal dip tanks were longitudinally sampled after vaccination using an
      inactivated trivalent FMD vaccine (South African Territories (SAT) 1, SAT 2 and
      SAT 3). Blood samples were collected fortnightly over four months and antibodies
      were measured using a liquid-phase blocking ELISA. Only 5%, 43%, and 16% of
      enrolled cattle had evidence of pre-existing antibody responses to the three SAT
      viruses at the beginning of the study (>=1.6 log10 titre for SAT 1-3
      respectively), which was 7-12 months after the last vaccination campaign.
      However, 14 days after vaccination this proportion increased to between 66% and
      93%, with SAT 2 having the highest proportion. Young animals (<1 year old) tended
      to have higher predicted baseline antibody levels that peaked by 14 days.
      Positive serological responses were transient and by 56 days post-vaccination
      antibody levels begun to decline below the threshold of 1.6 log10 titre.
      Predicted peak antibody levels only consistently reached 2.0 log10 for SAT 2.
      Serological responses for SAT 2 tended to be longer, but in most cases the
      duration of antibody levels was short-lived. More research is necessary to
      determine the reasons for the limited duration of antibody responses, especially
      among younger cattle, in order to achieve more effective prophylactic
      vaccination.

PMID- 30220401
TI  - Modeling the cost of eradicating livestock-associated methicillin-resistant
      staphylococcus aureus in countries with a high proportion of positive herds.
AB  - Due to an increased incidence of human infections, livestock-associated
      methicillin-resistant Staphylococcus Aureus (LA-MRSA) in pigs and its spread into
      the human population has been a major public and political issue in Denmark.
      Similar concerns are also being raised about LA-MRSA in other Western European
      countries. At a time when the proportion of LA-MRSA-positive pig farms was low,
      Norway adopted a 'trace and destroy' strategy aimed at keeping LA-MRSA out of the
      pig population. However, to date, no country with a high proportion of LA-MRSA
      positive pig herds has chosen to use an eradication strategy. This study analyses
      the cost and complexities of conducting an LA-MRSA eradication program in a
      situation where a large proportion of herds are positive. The total cost of the
      eradication program was estimated based on the following components: 1) planning,
      2) monitoring and testing, 3) cleaning and disinfection, 4) production gains and
      losses, 5) net reduction in breeding exports, and 6) loss of genetic progress,
      including the costs of a mitigating caesarean section strategy in breeding herds.
      Costs were related to the depopulation of 1 million sows, to gilt supply (as this
      was an important limiting factor during an eradication program in Denmark), and
      to aggregated losses linked to a temporary halt on breeding progress. Using
      conservative assumptions, the total eradication costs were estimated at ?1.8
      billion, broken down into: planning costs (3%), monitoring and testing (6%),
      cleaning and disinfection (19%), production gains and losses (33%), net loss from
      breeding exports (19%) and loss of genetic progress (20%). The long-term effects
      of an LA-MRSA eradication program for Danish pig production were uncertain and
      were therefore not taken into account in the analysis.

PMID- 30220402
TI  - Treatment of patients with restenosis of drug-eluting stents.

PMID- 30220403
TI  - Stuttering-like hesitation in speech during acute/post-acute phase of immune
      mediated encephalitis.
AB  - PURPOSE: Neurogenic stuttering may be evident after a lesion/dysfunction of wider
      neural networks. Here we present a case of acquired stuttering as the consequence
      of immune-mediated encephalitis. METHODS: The case of a 71-year old male who
      complained about the progressive onset of stuttering and disequilibrium as the
      consequence of immune-mediated encephalitis, is here reported. Administration of
      corticosteroid methylprednisolone was useful to recover from impairments. An in
      depth analysis of the electroencephalography (relative power of brain rhythms and
      source localization) during different phases of the disease/treatment was also
      realized. RESULTS: The patient showed a stuttering-like slowed speech with blocks
      and repetitions, especially at the beginning of words/sentences, with associated
      movements of the oro-facial muscles. Speech and general motor skills resulted
      slowed in their preparation/execution phases. Electroencephalography showed a
      "slowed" pattern, with delta/theta waves mainly in the prefrontal cortex and in
      sensorimotor networks. CONCLUSION: This case reports a probable immune-mediated
      encephalitis that resulted in acquired stuttering. The effect of "slowed"
      oscillatory brain activity on motor skills requesting sequencing and fine
      coordination (e.g. speech) could result in less "synchronized" systems, easily
      prone to disruptions.

PMID- 30220404
TI  - Envelope modulation spectral (EMS) analyses of solo reading and choral reading
      conditions suggest changes in speech rhythm in adults who stutter.
AB  - PURPOSE: A longstanding finding in persons who stutter is that stuttering
      frequency significantly reduces during choral reading when compared to the solo
      reading condition. Here, we tested the hypothesis that this decrease in
      stuttering frequency may be because speech of the normal speaker dictates the
      speech rhythm of a person who stutters. We used an automated, sensitive acoustic
      technique-Envelope Modulation Spectral (EMS) analysis- that allowed us to
      document speech rhythm. METHOD: Seventeen adults who stutter (AWS) read sentences
      under two conditions: solo reading and choral reading. Percentage of syllables
      stuttered (%SS), the rate of speech, and speech rhythm were calculated from the
      recorded sentences from AWS. Further, AWS speech rhythm during solo reading was
      compared with typical adults. EMS was extracted for the full signal and seven
      octave bands. From the extracted envelope six predictor variables (peak
      frequency, peak amplitude, energy in the spectrum 3-6 Hz, energy in the spectrum
      from 0 to 4 Hz, energy in the spectrum from 4 to 10 Hz, and the ratio of energy
      below4 Hz/above 4 Hz) were computed. RESULTS: Significant decrease in stuttering
      frequency and rate of speech was noticed in choral reading when compared to the
      solo reading condition. Further, analysis of EMS results suggested the
      statistically significant difference between two reading conditions (for peak
      frequency and peak amplitude), and between two groups for all predictor
      variables. CONCLUSION: Overall, current results highlight that decreases in
      stuttering during the choral reading is characterized by a decrease in rate and
      changes in some aspects of speech rhythm in Kannada speaking AWS.

PMID- 30220405
TI  - Appreciating the Intricacies of a Stuffy Nose.

PMID- 30220408
TI  - Clinical and Mutational Aspects of Non-small Cell Lung Cancer in a Latin American
      Reference Center.

PMID- 30220407
TI  - Nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in
      metastatic pancreatic adenocarcinoma (PACT-19): a randomised phase 2 trial.
AB  - BACKGROUND: Current treatment for metastatic pancreatic ductal adenocarcinoma
      includes combination chemotherapy, such as FOLFIRINOX or nab-paclitaxel plus
      gemcitabine. We investigated the activity of a novel four-drug regimen,
      consisting of cisplatin, nab-paclitaxel, capecitabine, and gemcitabine, compared
      with nab-paclitaxel plus gemcitabine, in the PACT-19 trial. METHODS: This single
      centre, randomised, open-label, phase 2 trial was done in San Raffaele Hospital
      in Italy. We enrolled patients aged 18-75 years with pathologically confirmed
      stage IV pancreatic ductal adenocarcinoma who had received no previous
      chemotherapy and had Karnofsky performance status of at least 70. Patients were
      randomly assigned (1:1) by computer-generated permutated block randomisation
      (block size of four) stratified by baseline concentration of carbohydrate antigen
      19-9 to PAXG (cisplatin 30 mg/m2, nab-paclitaxel 150 mg/m2, and gemcitabine 800
      mg/m2 on days 1 and 15 and oral capecitabine 1250 mg/m2 on days 1-28 every 4
      weeks), or nab-paclitaxel and gemcitabine alone (nab-paclitaxel 125 mg/m2 and
      gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 4 weeks). The primary endpoint
      was the proportion of patients who were progression-free at 6 months, analysed in
      the intention-to-treat population. Data cutoff was on March 31, 2018. The safety
      population included all patients who received at least one dose of study
      treatment. This trial is registered with ClinicalTrials.gov, number NCT01730222,
      and is now closed. FINDINGS: Between April 22, 2014, and May 30, 2016, we
      randomly assigned 83 patients to treatment: 42 patients to PAXG and 41 patients
      to nab-paclitaxel plus gemcitabine. At 6 months, 31 (74%, 95% CI 58-86) of 42
      patients in the PAXG group were alive and free from disease progression compared
      with 19 (46%, 31-63) of 41 patients in the nab-paclitaxel plus gemcitabine group.
      The most frequent grade 3 adverse events were neutropenia (12 [29%] of 42 in the
      PAXG group vs 14 [34%] of 41 in the nab-paclitaxel plus gemcitabine group),
      anaemia (nine [21%] vs nine [22%]), and fatigue (seven [17%] vs seven [17%]). The
      most common grade 4 adverse event was neutropenia (five [12%] in the PAXG group
      vs two [5%] in the nab-paclitaxel plus gemcitabine group). Two (5%) treatment
      related deaths occurred in the nab-paclitaxel plus gemcitabine group compared
      with none in the PAXG group. INTERPRETATION: Despite the small sample size, our
      findings suggest that the PAXG regimen warrants further investigation in a phase
      3 trial in patients with metastatic pancreatic ductal adenocarcinoma. FUNDING:
      Celgene.

PMID- 30220409
TI  - Quality indicators in gynecologic oncology.

PMID- 30220410
TI  - Diagnostic procedure in suspected Graves' disease.
AB  - Diagnostic procedure in suspected Graves' disease has never been studied
      scientifically and actual practice seems quite variable, notably between
      countries. Recommendations are few and weak (expert opinion). This article
      presents the recommendations of an expert consensus meeting organized by the
      French Society of Endocrinology in 2016. In case of clinically suspected
      thyrotoxicosis, the first-line biological assessment is of thyroid-stimulating
      hormone (TSH). Free T4 and possibly free T3 assays assess biological severity and
      are necessary for treatment efficacy monitoring. Positive diagnosis of Graves'
      disease after biological confirmation of thyrotoxicosis does not always require
      complementary etiological examinations if clinical presentation is unambiguous,
      notably including extra-thyroid signs. Otherwise, first-line anti-TSH-receptor
      (TSH-R) antibody screening is recommended for its good intrinsic performance
      (sensitivity and specificity) and ease of access in France. Scintigraphy is
      reserved to rare cases of Graves' disease with negative antibody findings or when
      another etiology is suspected. Thyroid ultrasound scan may be contributive, but
      is not recommended in first line.

PMID- 30220411
TI  - Effects of acute exposure to dispersed oil and burned oil residue on long-term
      survival, growth, and reproductive development in polar cod (Boreogadus saida).
AB  - The present study investigates the potential long-term physiological effects on
      maturing polar cod (Boreogadus saida), an Arctic key species, after an acute
      exposure (48 h) to environmentally realistic concentrations of either
      mechanically dispersed oil (MDO), chemically dispersed oil (CDO) or burned oil
      residues (BO) (N = 58-60 per treatment). Following exposure, fish were monitored
      in a common tank supplied with clean water for a seven-month period coinciding
      with the period of reproductive development. Females exposed to BO residues were
      more frequently found in an earlier phase of gonadal maturation compared to
      unexposed females while no effects of different oil spill response (OSR) actions
      were seen in the reproductive development of males. Mechanically and chemically
      dispersed oil induced a transient short-term reduction in growth in the first
      week post-exposure. Overall, no significant long-term effects of exposure were
      seen in growth or mortality. Ultimately, this study provides information for the
      assessment of population consequences of different OSR actions as part of a net
      environmental benefit analysis.

PMID- 30220413
TI  - Ryanodine Receptor Open Times Are Determined in the Closed State.
AB  - The ryanodine receptor (RyR) ion channel releases Ca2+ from intracellular stores
      by conducting Ca2+ but also by recruiting neighboring RyRs to open, as RyRs are
      activated by micromolar levels of cytosolic Ca2+. Using long single-RyR
      recordings of the cardiac isoform (RyR2), we conclude that Ca2+ binding to the
      cytosolic face of RyR while the channel is closed determines the distribution of
      open times. This mechanism explains previous findings that RyR is not activated
      by its own fluxed Ca2+. Our measurements also bolster previous findings that
      luminal [Ca2+] can affect both the cytosolic activation and inactivation sites
      and that RyR has different gating modes for the same ionic conditions.

PMID- 30220414
TI  - Usefulness of Cardiac Magnetic Resonance Imaging in Patients With Acute
      Spontaneous Coronary Artery Dissection.
AB  - Cardiac magnetic resonance (CMR) has significant diagnostic and prognostic
      utility in myocardial infarction evaluation. However, its application in
      spontaneous coronary artery dissection (SCAD) is not described. Patients with
      confirmed SCAD who had CMR performed within 8 days of the index SCAD were
      reviewed. Clinical variables including demographics and medical history were
      recorded. CMR indexes, including myocardial delayed enhancement (MDE),
      microvascular obstruction, perfusion defects, left ventricular ejection fraction,
      and wall motion score index were measured. A total of 18 patients (all women,
      mean age 47.1 years) were included. Overall burden of atherosclerotic risk
      factors was low; 3 had a previous SCAD. Two patients underwent CMR before
      coronary angiography, whereas the others received CMR thereafter. Mean time
      between SCAD diagnosis and CMR completion was 2.7 days (range 0 to 8). Mean left
      ventricular ejection fraction and wall motion score index were 56.1% and 1.27,
      respectively. A total of 15 patients had MDE consistent with myocardial
      infarction in the SCAD distribution(s) identified on coronary angiography, with 8
      patients having concomitant microvascular obstruction. Ten patients had
      transmural MDE. At follow-up (mean 386 days), all patients were alive;
      extracoronary vascular abnormalities were identified in 14; 6 had recurrent chest
      pain; and 2 had recurrent SCAD. Both patients with recurrent SCAD had no unique
      features on CMR to predict a future event. In conclusion, CMR provided
      significant value in clarifying the diagnosis and assessing for adverse sequelae
      after acute SCAD. Further studies are needed to determine its role in SCAD
      prognostication.

PMID- 30220415
TI  - Do Not Forget Physical Activity and Cardiorespiratory Fitness.

PMID- 30220416
TI  - Primary and Secondary Diastolic Dysfunction in Heart Failure With Preserved
      Ejection Fraction.
AB  - Approximately 50% of patients with symptoms and signs of heart failure have a
      left ventricular ejection fraction (LVEF) >=50% and are often simply referred to
      as 'heart failure with preserved EF', 'HFpEF'. Many of such patients have HF
      secondary to specific cardiac conditions (i.e., valvular or pericardial disease)
      in which the symptoms and signs occur despite the LVEF being preserved due to
      diastolic dysfunction secondary to the underlying disease (secondary HFpEF),
      differently from those HFpEF patients in which the impaired LV filling is due to
      a primary diastolic dysfunction (primary HFpEF). When primary HFpEF patients are
      properly diagnosed, they appear to have a milder form of HF with a lower
      cardiovascular mortality compared with HFrEF and secondary HFpEF population, but
      a risk of HF hospitalization that is significantly higher than patients with
      similar cardiovascular risk factors but without the diagnosis of HFpEF. We herein
      review the diagnostic approach to HFpEF and present a differential diagnosis of
      HFpEF in a primary and secondary form.

PMID- 30220417
TI  - Usefulness of Asymmetric Dimethylarginine to Predict Outcomes After Heart
      Transplantation.
AB  - Asymmetric dimethylarginine (ADMA) is a key mediator of vascular homeostasis and
      an independent predictor of the development of accelerated cardiac allograft
      vasculopathy after heart transplantation. However, its association with clinical
      outcomes in heart transplant recipients has not been described. Plasma levels of
      ADMA were assayed within 8 weeks following transplantation (baseline) using a
      competitive enzyme-linked immunosorbent assay. The primary end point was the
      composite of nonfatal myocardial infarction, percutaneous coronary intervention,
      retransplantation, or death at 5-year follow-up. Kaplan-Meier curves were
      generated to assess the association between baseline ADMA levels (stratified at
      0.70 uM, a previously established cutoff) and cumulative event-free survival.
      Multivariate Cox regression was performed to adjust for other candidate
      predictors. In 69 heart transplant recipients at Stanford, the primary end point
      occurred in 11 patients (16%)-4 percutaneous coronary intervention, 1
      retransplant, and 6 deaths-during 5-years follow-up. Patients with baseline ADMA
      >=0.70 uM had lower cumulative 5-year event-free survival (77% vs 93%, p =
      0.059). In multivariate Cox analysis, baseline ADMA was the only significant
      predictor of the primary end point (hazard ratio 1.33, 95% confidence interval
      1.03 to 1.72 per 0.1 uM; p = 0.031). This association remained significant even
      after restricting the end point to death or retransplantation (hazard ratio 1.48,
      95% confidence interval 1.12 to 1.97 per 0.1 uM; p = 0.006). In conclusion,
      elevated baseline plasma levels of ADMA independently predicted 5-year clinical
      outcomes after heart transplantation, suggesting that ADMA has potential
      prognostic value in the heart transplant arena.

PMID- 30220418
TI  - Meta-Analysis Comparing Percutaneous Coronary Revascularization Using Drug
      Eluting Stent Versus Coronary Artery Bypass Grafting in Patients With Left
      Ventricular Systolic Dysfunction.
AB  - The relative safety and efficacy of percutaneous coronary intervention (PCI) with
      drug-eluting stent (DES) and coronary artery bypass grafting (CABG) in patients
      with left ventricular (LV) systolic dysfunction remains controversial; therefore
      we conducted this meta-analysis to identify the optimal strategy for such
      cohorts. A comprehensive search of the electronic databases including PubMed,
      EMBASE, and Cochrane Library from January 1, 2003 to March 1, 2018 was performed
      to identify the eligible adjusted observational studies. The primary end point
      was all-cause death during the longest follow-up, and the generic inverse
      variance random-effect model was used to estimate the pooled hazard ratios (HRs)
      with 95% confidence intervals (CIs). Eight adjusted observational studies
      involving 10,268 patients were included. Compared with CABG, PCI with DES was
      associated with higher risk of all-cause mortality (HR 1.36, 95% CI 1.16 to
      1.60), cardiac mortality (HR 2.20, 95% CI 1.63 to 2.95), myocardial infarction
      (HR 1.69, 95% CI 1.28 to 2.24), and repeat revascularization (HR 4.95, 95% CI
      3.28 to 7.46) in patients with coronary artery disease and LV systolic
      dysfunction. Besides, separate analysis of patients with LV ejection fraction
      <35% or left main and/or multivessel disease obtained similar results compared
      with the overall analysis. However, DES and CABG shared similar rates of stroke
      (HR 0.92, 95% CI 0.67 to 1.26). In conclusion, CABG appears to be superior to PCI
      with DES for patients with coronary artery disease and LV systolic dysfunction,
      particularly in patients with severe LV systolic dysfunction or those with left
      main and/or multivessel disease.

PMID- 30220419
TI  - Prognostic Role of Cardiac Magnetic Resonance in Arrhythmogenic Right Ventricular
      Cardiomyopathy.
AB  - We sought to evaluate the prognostic role of cardiac magnetic resonance (CMR) in
      patients with definite, borderline and possible diagnosis of arrhythmogenic right
      ventricular cardiomyopathy (ARVC) as defined by the International Task Force (TF)
      in 2010. CMR was performed in 175 patients: 52 with definite, 50 with borderline
      and 73 possible ARVC. Abnormal-CMR was defined as the presence of >=1 CMR
      abnormalities (including abnormalities of right ventricular and left ventricular
      wall motion, fat infiltration, late gadolinium enhancement, dilation and
      dysfunction of either ventricles). During the follow-up time 35 patients had hard
      cardiac events (sudden cardiac death, appropriate implantable cardioverter
      defibrillator shock and resuscitated cardiac arrest), and 34 of them occurred in
      patients with abnormal-CMR (negative predictive value = 96.9%). At the
      multivariate Cox-regression analysis LV involvement at CMR (fat infiltration
      and/or late gadolinium enhancement), and episode of nonsustained ventricular
      tachycardia (NSVT) were independent predictors of cardiac events in both the
      whole population (LV involvement: HR 3.69, 95% CI 1.57-8.65, p = 0.0002; NSVT: HR
      5.8, 95% CI 2.82-11.9, p < 0.0001), and in the group of patients with definite
      ARVC (LV involvement: HR 3.03, 95% CI 1.15 to 8.02, p = 0.02; NSVT: HR 12.1, 95%
      CI 4.02-36.5, p < 0.0001). In conclusion, CMR evidence of LV involvement is a
      strong independent predictor of cardiac events in patients with definite,
      borderline or possible ARVC diagnosis. Abnormal CMR has very high negative
      predictive value for hard cardiac events.

PMID- 30220420
TI  - Meta-Analysis Comparing Complete or Culprit Only Revascularization in Patients
      With Multivessel Disease Presenting With Cardiogenic Shock.
AB  - The optimal strategy for patients with an acute myocardial infarction (MI) and
      multivessel (MV) coronary artery disease complicated by cardiogenic shock (CS)
      remains unknown. We conducted a meta-analysis of all randomized controlled trials
      and observational studies that reported adjusted effect measures to evaluate the
      association of MV-PCI (percutaneous coronary intervention), compared with culprit
      only (C)-PCI, with cardiovascular events in patients admitted for CS and MV
      disease. We identified 12 studies (n = 1 randomized controlled trials, n = 11
      observational) that included 7,417 patients (n = 1,809 treated with MV-PCI and n
      = 5,608 with C-PCI). When compared with C-PCI, MV-PCI was not associated with an
      increased risk of short-term death (odds ratio [OR] 1.14, 95% confidence interval
      [CI] 0.87 to 1.48, p = 0.35 and adjusted OR [ORadj] 1.00, 95% CI 0.70 to 1.43, p
      = 1.00). In-hospital and/or short-term mortality tended to be higher with MV-PCI,
      when compared with C-PCI, for CS patients needing dialysis (beta 0.12, 95% CI
      from 0.049 to 0.198; p= 0.001), whereas MV-PCI was associated with lower in
      hospital and/or short-term mortality in patients with an anterior MI (beta 
      0.022, 95% CI -0.03 to -0.01; p <0.001). MV-PCI strategy was associated with a
      more frequent need for dialysis or contrast-induced nephropathy after
      revascularization (OR 1.36, 95% CI 1.06 to 1.75, p = 0.02). In conclusion, MV-PCI
      seems not to increase risk of death during short- or long-term follow-up when
      compared with C-PCI in patients admitted for MV coronary artery disease and MI
      complicated by CS. Furthermore, it appears a more favorable strategy in patients
      with anterior MI, whereas the increased risk for AKI and its negative prognostic
      impact should be considered in decision-making process. Further studies are
      needed to confirm our hypothesis on in these subpopulations of CS patients.

PMID- 30220422
TI  - Reduction in voluntary food intake, but not fasting, stimulates hypothalamic
      gonadotropin-inhibitory hormone precursor mRNA expression in chicks under heat
      stress.
AB  - Heat stress is an issue of rising concern across the globe. Recently, we found
      that mRNA expression of gonadotropin-inhibitory hormone (GnIH), an orexigenic
      neuropeptide, was increased in the heat-exposed chick brain when food intake was
      reduced. The aim of the current study was to examine mRNA expression of GnIH and
      of the glucocorticoid receptors (GRs) in the hypothalamus as well as the plasma
      corticosterone (CORT) and metabolites in 14-d-old chicks exposed to a high
      ambient temperature (HT; 40 +/- 1  degrees C for 1 or 5 h) or a control
      thermoneutral temperature (CT; 30 +/- 1  degrees C), either with free access to
      food or fasted. Heat stress caused a voluntary reduction of food intake and
      reduced plasma triacylglycerol concentration, but increased rectal temperature
      and plasma CORT and glucose concentrations (P < 0.05). Heat stress also increased
      (P < 0.05) the expression of diencephalic GnIH mRNA in chicks when they reduced
      food intake voluntarily, but did not do so under fasting conditions. Although the
      expression of GR mRNA was not altered as a result of heat stress, its expression
      was decreased (P < 0.05) in fasted chicks at 5 h in comparison with fed chicks.
      In addition, the rectal temperature of fasted chicks was lower than that of fed
      chicks under both CT and HT. In conclusion, voluntary reduction of food intake
      caused an increase in brain GnIH mRNA expression, plasma CORT, and body
      temperature in chicks under heat stress. Interestingly, brain GnIH mRNA
      expression was not induced by heat stress in fasted chicks and was not
      accompanied by a decrease in rectal temperature. These results suggest that the
      increased expression of brain GnIH mRNA in chicks under heat stress could be a
      consequence of a mechanism mediated by the voluntary reduction of food intake,
      but that it is not a consequence of fasting.

PMID- 30220423
TI  - High-Resolution Ultrasound Visualization of Pacinian Corpuscles.
AB  - The aim of this study was to evaluate the possibility of visualizing Pacinian
      corpuscles in the palm of the hand with high-resolution ultrasound (HRUS). In
      this prospective study, HRUS with a high-frequency probe (22 MHz) was used. The
      palms of two fresh cadaveric hands were screened for potential Pacinian
      corpuscles. Still ultrasound images and dynamic video sequences were obtained. In
      five regions with large amounts of suspected Pacinian corpuscles, tissue blocks
      were excised and histologically processed, and corresponding slices were compared
      with ultrasound images. Further, the transverse diameters of five Pacinian
      corpuscles, at the level of the metacarpal heads in the palm, were assessed on
      both sides (in total 100) in healthy volunteers. On ultrasound, Pacinian
      corpuscles presented as echolucent dots in the subcutis, adjacent to digital
      nerves and vessels and located 2-3 mm beneath the surface. On histologic
      sections, these echolucent dots corresponded to Pacinian corpuscles with respect
      to their position and topographic relationships. The mean transverse diameter for
      all volunteers was 1.40 +/- 0.23 mm (range: 0.8-2.2 mm). This study confirms the
      ability to reliably visualize Pacinian corpuscles with HRUS, which contributes to
      our basic understanding of ultrasonographically visible subcutaneous structures
      and may enhance the diagnosis of pathologies related to Pacinian corpuscles.

PMID- 30220424
TI  - Familial financial stress and child internalizing behaviors: The roles of
      caregivers' maltreating behaviors and social services.
AB  - Based on the family stress model and the stress-buffering model, the present
      study examines the relationship between caregivers' financial stress and child
      internalizing problem behaviors, the mediating role of caregiver maltreating
      behaviors, and whether social services for caregivers buffer this relationship.
      The current study is based on data from wave two of the National Survey of Child
      and Adolescent Well-Being dataset (N = 2670). Results indicated increased high
      familial financial stress was associated with child internalizing problems.
      Caregivers' psychological aggression, physical assault, child neglect, and sexual
      maltreatment emerged as mechanisms mediating this relationship. Tangible service
      and social network service were found to mitigate the deleterious effect of
      financial stress on child internalizing behaviors, but primarily for those whom
      financial stress was high. These findings highlight the role perceived financial
      stress has on potential maltreatment and child outcomes, rather than relying on
      objective measures of economic status. Implications for social services focused
      interventions for children and caregivers coping with high levels of perceived
      financial stress are discussed.

PMID- 30220425
TI  - Interpersonal violence: identification of associated features in a clinical
      sample.
AB  - Violence is a burdensome problem in daily psychiatric practice, even though the
      diagnosisof a mental disorder is not sufficient to determine a violent behavior;
      therefore, other factors are involved. We predicted that the participants could
      be distributed in two groups (e.g. high versus low violence-maltreatment groups)
      because this grouping would better describe specific patterns of associations in
      a clinical sample. We aimed to investigate the relation between interpersonal
      violence and maltreating experiences in childhood. Affective states and personal
      functioning were also explored as meaningful outcomes. Consecutive patients (N =
      101) admitted to a psychiatric unit were evaluated with the Risky Families
      Questionnaire, the Psychological Maltreatment Review, the Karolinska
      Interpersonal Violence Scale (KIVS), the Positive and Negative Affect Schedule
      and the Personal and Social Performance Scale. Single, with average education and
      unemployed individuals showed significantly higher KIVS scores. High levels of
      interpersonal violence (IV) in childhood correlated with a harsh family climate
      in early life. Moreover, IV correlated with perceived parental maltreatment and
      did not with parental support. The cluster analysis identified two clusters of
      patients. The first (n = 41) showed negative dysfunctional experiences; the
      second (n = 60) showed a more positive perception of parental support.The
      impairment of social functioning and emotions regulation are both involved in
      this complex relation. The study supports the hypothesis of a clustering of
      patients that needs tailored management of violence causes and consequences.

PMID- 30220426
TI  - Estimation of peak capacity based on peak simulation.
AB  - Peak capacity (PC) is a key concept in chromatographic analysis, nowadays of
      great importance for characterising complex separations as a criterion to find
      the most promising conditions. A theoretical expression for PC estimation can be
      easily deduced in isocratic elution, provided that the column plate count is
      assumed constant for all analytes. In gradient elution, the complex dependence of
      peak width with the gradient program implies that an integral equation has to be
      solved, which is only possible in a limited number of situations. In 2005, Uwe
      Neue developed a comprehensive theory for the calculation of PC in gradient
      elution, which is only valid for certain situations: single linear gradients,
      absence of delays and extra-column effects, Gaussian peaks and constant plate
      count. Going beyond these limitations implies resolving algebraic expressions
      that unfortunately cannot be integrated. In this work, PC is predicted for
      multiple situations based on peak simulation. The approach is more general and
      can be applied for situations out of the scope of the Neue outline, such as
      complex multi-linear gradients, including asymmetrical peaks. The plots of PC
      versus retention time of the last eluted solute give rise to Pareto fronts, and
      can be useful for the probabilistic enhancement of peak resolution in situations
      where complex multi-analyte samples are processed.

PMID- 30220427
TI  - Separation of highly charged (+5 to +10) amphipathic alpha-helical peptide
      standards by cation-exchange and reversed-phase high-performance liquid
      chromatography.
AB  - We are currently examining the potential of amphipathic cationic alpha-helical
      peptides as a new generation of peptide standards for both cation-exchange high
      performance liquid chromatography and reversed-phase chromatography. Thus,
      amphipathic peptides are particularly suitable for high-performance liquid
      chromatography standards due to the preferred binding of the non-polar face to
      the hydrophobic stationary phase of reversed-phase packings or the preferred
      binding of the polar face to the charged/hydrophilic stationary phase of cation
      exchange packings. The ability of different reversed-phase or cation-exchange
      matrices to separate mixtures of peptide standards with only subtle
      hydrophilicity/hydrophobicity variations in both the non-polar and polar face of
      the peptides can then be assessed. Currently, we have designed de novo a mixture
      of six 26-residue all D-conformation amphipathic cationic alpha-helical peptides
      with a single, positively charged lysine residue in the center of the non-polar
      face and an increasing number of lysine residues (4-9 residues) replacing neutral
      residues in the polar face, resulting in an overall net positive charge of +5 to
      +10. Thus, the non-polar, preferred reversed-phase chromatography binding face
      remains constant, with only the polar face varying in
      hydrophilicity/hydrophobicity. Interestingly, even with the non-polar face
      remaining constant, reversed-phase columns of varying functional group properties
      (e.g., C8, C18, phenyl, polar endcapped, polar embedded) and porosity (porous
      versus superficially porous) were able to separate the six peptides in aq.
      TFA/acetonitrile gradients, albeit with different selectivities. The value of the
      standards in cation-exchange chromatography was expressed by monitoring the
      requirement of acetonitrile (0-40% in the mobile phase) to overcome hydrophobic
      interactions of the peptides with the cation-exchange matrix matrix when eluting
      with sodium perchlorate gradients at pH 6.5. Interestingly, the resolution of the
      higher charged peptides (+8,+9,+10) was particularly sensitive to acetonitrile
      levels. Our results clearly demonstrate the excellent potential of these novel
      peptide standards to enable optimal column choice and mobile phase conditions for
      reversed-phase chromatography and cation-exchange chromatography for peptide
      separations.

PMID- 30220428
TI  - Method development for the certification of a ginsenoside calibration solution
      via liquid chromatography with absorbance and mass spectrometric detection.
AB  - The research presented here describes the development of two analytical methods
      for use in the certification of a ginsenoside calibration solution Standard
      Reference Material (SRM) 3389 consisting of seven ginsenosides: Rg1, Re, Rf, Rb1,
      Rc, Rb2, and Rd. The new methods utilized the liquid chromatographic (LC)
      separation of ginsenoside mixtures with absorbance detection (UV) and mass
      spectrometry (MS). Ginsenosides Rb3, Rg2, Rg3, Rh1, and Rh2 were evaluated for
      use as internal standards for LC/MS measurements. The 12 ginsenosides were
      baseline resolved by gradient elution LC/UV, with an initial mobile phase
      composition of 22% acetonitrile and 78% water, flow rate of 0.7 mL/min, and
      column temperature of 25  degrees C. The work presented here includes a detailed
      investigation into the optimization of the chromatographic conditions to minimize
      measurement biases that result from unresolved constituents. Temperature and
      mobile phase composition are known to play a significant role in column
      selectivity; however, flow rate is expected to influence primarily the separation
      efficiency and detection sensitivity. In the current study, column selectivity
      changed with changes in flow rate and the relative retention of ginsenoside Rg2
      and Rh1 changed as the flow rate increased from 0.6 mL/min to 1.0 mL/min.

PMID- 30220431
TI  - Surfactant and lung function following cardiac surgery.

PMID- 30220429
TI  - Hydrophilic interaction liquid chromatography-tandem mass spectrometry for the
      quantitative analysis of mammalian-derived inositol poly/pyrophosphates.
AB  - Although myo-inositol pyrophosphates such as diphosphoinositol pentakisphosphate
      (InsP7) are important in biology, little quantitative information is available
      regarding their presence in mammalian organisms owing to the technical
      difficulties associated with accurately detecting these materials in biological
      samples. We have developed an analytical method whereby InsP7 and its precursor
      inositol hexakisphosphate (InsP6) are determined directly and sensitively using
      tandem mass spectrometry coupled with hydrophilic interaction liquid
      chromatography (HILIC). InsP6 and InsP7 peak symmetry is influenced greatly by
      the buffer salt composition and pH of the mobile phase used in HILIC analysis.
      The use of 300 mM ammonium carbonate (pH 10.5) as an aqueous mobile phase
      resolves InsP6 and InsP7 on a polymer-based amino HILIC column with minimal peak
      tailing. Method validation shows that InsP6 and InsP7 can be quantitated from 20
      500 pmol with minimal intra-day/inter-day variance in peak area and retention
      time. The concentration of InsP6 in C57BL/6J mouse brain (40.68 +/- 3.84 pmol/mg
      wet weight) is successfully determined. HILIC-MS/MS analysis using HEK293 culture
      cells confirms previous observations that InsP7 is induced by NaF treatment and
      ectopic expression of InsP6K2, a primary kinase for InsP7 synthesis. Furthermore,
      this analysis reveals the abundance of InsP6 (50.46 +/- 18.57 pmol/106 cells) and
      scarcity of InsP7 in human blood cells. The results demonstrate that HILIC-MS/MS
      analysis can quantitate endogenous InsP6 and InsP7 in mouse and human samples,
      and we expect that the method will contribute to further understanding of InsP7
      functions in mammalian pathobiology.

PMID- 30220430
TI  - Ion mobility spectrometry and high resolution mass-spectrometry as methodologies
      for rapid identification of the last generation of new psychoactive substances.
AB  - A new drug trafficking trend has been observed in the last years by the
      introduction in the black market of new psychoactive substances (NPS) in order to
      difficult competent authority controls. In this study, ion mobility spectrometry
      (IMS) and high-resolution mass-spectrometry (HRMS) were proposed as vanguard and
      rearguard methodologies for the rapid identification of the last generation of
      NPS in seizures. The combined use of IMS and HRMS has been evaluated through the
      analysis of 24 NPS seized from 2016 to 2018 in Valencia (Spain) to demonstrate
      the utility of this approach. The characteristic reduced mobility (K0) values for
      seized NPS were determined and mass-mobility relationships were proposed and
      evaluated for the main NPS families: amphetamine and cathinone derivatives, and
      synthetic cannabinoids. IMS did not allow a unequivocal identification by itself;
      so, HRMS analysis was employed as rearguard confirmation methodology for the
      right identification of NPS. Thus, the combined use of IMS and HRMS can be
      considered as promising alternative for the rapid screening and identification of
      NPS in seizures.

PMID- 30220434
TI  - Sepsis-induced thrombus formation and cell-specific HIFs.

PMID- 30220433
TI  - ClinPred: Prediction Tool to Identify Disease-Relevant Nonsynonymous Single
      Nucleotide Variants.
AB  - Advances in high-throughput DNA sequencing have revolutionized the discovery of
      variants in the human genome; however, interpreting the phenotypic effects of
      those variants is still a challenge. While several computational approaches to
      predict variant impact are available, their accuracy is limited and further
      improvement is needed. Here, we introduce ClinPred, an efficient tool for
      identifying disease-relevant nonsynonymous variants. Our predictor incorporates
      two machine learning algorithms that use existing pathogenicity scores and,
      notably, benefits from inclusion of normal population allele frequency from the
      gnomAD database as an input feature. Another major strength of our approach is
      the use of ClinVar-a rapidly growing database that allows selection of
      confidently annotated disease-causing variants-as a training set. Compared to
      other methods, ClinPred showed superior accuracy for predicting pathogenicity,
      achieving the highest area under the curve (AUC) score and increasing both the
      specificity and sensitivity in different test datasets. It also obtained the best
      performance according to various other metrics. Moreover, ClinPred performance
      remained robust with respect to disease type (cancer or rare disease) and
      mechanism (gain or loss of function). Importantly, we observed that adding allele
      frequency as a predictive feature-as opposed to setting fixed allele frequency
      cutoffs-boosts the performance of prediction. We provide pre-computed ClinPred
      scores for all possible human missense variants in the exome to facilitate its
      use by the community.

PMID- 30220432
TI  - Genetic Association of Albuminuria with Cardiometabolic Disease and Blood
      Pressure.
AB  - Excretion of albumin in urine, or albuminuria, is associated with the development
      of multiple cardiovascular and metabolic diseases. However, whether pathways
      leading to albuminuria are causal for cardiometabolic diseases is unclear. We
      addressed this question using a Mendelian randomization framework in the UK
      Biobank, a large population-based cohort. We first performed a genome-wide
      association study for albuminuria in 382,500 individuals and identified 32 new
      albuminuria loci. We constructed albuminuria genetic risk scores and tested for
      association with cardiometabolic diseases. Genetically elevated albuminuria was
      strongly associated with increased risk of hypertension (1.38 OR; 95% CI, 1.27
      1.50 per 1 SD predicted increase in albuminuria, p = 7.01 * 10-14). We then
      examined bidirectional associations of albuminuria with blood pressure which
      suggested that genetically elevated albuminuria led to higher blood pressure
      (2.16 mmHg systolic blood pressure; 95% CI, 1.51-2.82 per 1 SD predicted increase
      in albuminuria, p = 1.22 * 10-10) and that genetically elevated blood pressure
      led to more albuminuria (0.005 SD; 95% CI 0.004-0.006 per 1 mmHg predicted
      increase in systolic blood pressure, p = 2.45 * 10-13). These results support the
      existence of a feed-forward loop between albuminuria and blood pressure and imply
      that albuminuria could increase risk of cardiovascular disease through blood
      pressure. Moreover, they suggest therapies that target albuminuria-increasing
      processes could have antihypertensive effects that are amplified through
      inhibition of this feed-forward loop.

PMID- 30220436
TI  - An overview of the effect of pyrolysis process parameters on biochar stability.
AB  - Biochar produced from biomass pyrolysis is becoming a powerful tool for carbon
      sequestration and greenhouse gas (GHG) emission reduction. Biochar C
      recalcitrance or biochar stability is the decisive property determining its
      carbon sequestration potential. The effect of pyrolysis process parameters on
      biochar stability is becoming a frontier of biochar study. This review discussed
      comprehensively how and why biomass compositions and physicochemical properties
      and biomass processing conditions such as pyrolysis temperature and reaction
      residence time affect the stability of biochar. The review found that relative
      high temperature (400-700  degrees C), long reaction residence time, slow heating
      rate, high pressure, the presence of some minerals and biomass feedstock of high
      lignin content with large particle size are preferable to biochar stability.
      However, challenges exist to mediate the trade-offs between biochar stability and
      other potential wins. Strategies were then proposed to promote the utilization of
      biochar as a climate change mitigation tool.

PMID- 30220435
TI  - Clinical infrared microscopic imaging: An overview.
AB  - New developments in Mid-infrared microscopic imaging instrumentation and data
      analysis have turned this method into a conventional technique. This imaging
      method offers a global analysis of samples, with a resolution close to the
      cellular level enabling the acquisition of local molecular expression profiles.
      It is possible to get chemo-morphological information about the tissue status,
      which represents an essential benefit for future analytical interpretation of
      pathological changes of tissue. In this review, we give an overview of Mid
      infrared microscopic imaging and its applications in clinical research.

PMID- 30220437
TI  - The 7th International Symposium on Sourdough - "Sourdough for health".

PMID- 30220438
TI  - Exploiting synergies of sourdough and antifungal organic acids to delay fungal
      spoilage of bread.
AB  - Fungal spoilage of bread remains an unsolved issue in bread making. This work
      aims to identify alternative strategies to conventional preservatives in order to
      prevent or delay fungal spoilage of bread. The minimum inhibitory concentration
      (MIC) of bacterial metabolites and chemical preservatives was evaluated in vitro,
      and compared to their in situ activity in baking trials. Calcium propionate,
      sorbic acid, 3-phenyllactic acid, ricinoleic acid, and acetic acid were tested
      both individually and in combination at their MIC values against Aspergillus
      niger and Penicillium roqueforti. The combination of acetic acid with propionate
      and sorbate displayed additive effects against the two fungi. For these reasons,
      we introduced sourdough fermentation with specific strains of lactobacilli, using
      wheat or flaxseed, in order to generate acetate in bread. A combination of
      Lactobacillus hammesii and propionate reduced propionate concentration required
      for shelf life extension of wheat bread 7-fold. Flaxseed sourdough bread
      fermented with L. hammesii, excluding any preservative, showed a shelf life 2
      days longer than the control bread. The organic acid quantification indicated a
      higher production of acetic acid (33.8 +/- 4.4 mM) when compared to other
      sourdough breads. Addition of 4% of sucrose to sourdough fermentation with L.
      brevis increased the mould free shelf-life of bread challenged with A. niger by 6
      days. The combination of L. hammesii sourdough and the addition of ricinoleic
      acid (0.15% or 0.08%) prolonged the mould free shelf-life by 7-8 days for breads
      produced with wheat sourdoughs. In conclusion, the in vitro MIC of bacterial
      metabolites and preservatives matched the in situ antifungal effect. Of the
      different bacterial metabolites evaluated, acetic acid had the most prominent and
      consistent antifungal activity. The use of sourdough fermentation with selected
      strains able to produce acetic acid allowed reducing the use of chemical
      preservatives.

PMID- 30220439
TI  - 'Being human' and the 'moral sidestep' in drug policy: Explaining government
      inaction on opioid-related deaths in the UK.
AB  - BACKGROUND: With drug-related deaths at record levels in the UK, the government
      faces two potential sources of pressure to implement more effective policies. One
      source is the individuals and families who are most likely to suffer from such
      deaths; i.e. working class people living in de-industrialised areas. The other
      source is experts who argue for different policy on the basis of research
      evidences. AIM: This article aims to explain why, in the face of these two
      potential sources of pressure, the UK government has not implemented effective
      measures to reduce deaths. METHOD: The article uses critical realist discourse
      analysis of official documents and ministerial speeches on recent British drug
      policy (2016-2018). It explore this discourse through the theoretical lens of
      Archer's (2000) ideas on 'being human' and by drawing on Sayer's (2005) work on
      the 'moral significance of class'. RESULTS: Members of economically 'residual'
      groups (including working class people who use heroin) are excluded from
      articulating their interests in 'late welfare capitalism' in a project of
      depersonalising 'class contempt' through which politicians cast the people most
      likely to die as passive, 'vulnerable' 'abjects'. Conservative politicians
      dismiss 'evidence-based' ideas on the reduction of drug-related death through a
      'moral sidestep'. They defend policy on the basis of its relevance to
      conservative moral principles, not effectiveness. This is consistent with the
      broader moral and political pursuit of partial state shrinkage which Conservative
      politicians and the social groups they represent have pursued since the 1970s.

PMID- 30220440
TI  - Caulobacter zeae sp. nov. and Caulobacter radicis sp. nov., novel endophytic
      bacteria isolated from maize root (Zea mays L.).
AB  - Four bacterial strains designated 410T, 441, 695T and 736 were isolated from
      maize root in Beijing, P. R. China. Based on 16S rRNA gene phylogeny, the four
      strains formed two clusters in the genus Caulobacter. Since strain 441 was a
      clonal variety of strain 410T, only three strains were selected for further
      taxonomic studies. The whole genome average nucleotide identity (ANI) value
      between strains 410T and 695T was 94.65%, and both strains shared less than
      92.10% ANI values with their close phylogenetic neighbors Caulobacter vibrioides
      DSM 9893T, Caulobacter segnis ATCC 21756T and Caulobacter flavus CGMCC 1.15093T.
      Strains 410T and 695T contained Q-10 as the sole ubiquinone and their major fatty
      acids were C16:0, 11-methyl C18:1omega 0, 11-methyl C18: 1omega7c, summed feature
      3 (C16:1omega7c and/or C16:1omega 1omega7c and/or C16: 1omega6c) and summed
      feature 8 (C18:1omega7c and/or C18:1omega 1omega7c and/or C18: 1omega6c). Their
      major polar lipids consisted of glycolipids and phosphatidylglycerol, and
      phenotypic tests differentiated them from their closest phylogenetic neighbors.
      Based on the results obtained, it is proposed that the three strains represent
      two novel species, for which the names Caulobacter zeae sp. nov. (type strain
      410T=CGMCC 1.15991=DSM 104304) and Caulobacter radicis sp. nov. (type strain
      695T=CGMCC 1.16556=DSM 106792) are proposed.

PMID- 30220441
TI  - [Brucellosis with hepatic lesions: A diagnosis to keep in mind].
AB  - INTRODUCTION: Brucellosis is a rare infection in France and its wide spectrum of
      clinical presentation can be a diagnostic challenge. CASE REPORT: We report here
      the case of a 76-year-old Tunisian-born woman referred for fatigue, weight loss,
      intermittent fever, and pain in the right upper quadrant, along with hepatic
      lesions on CT-scan, MRI and PET-FDG suggesting malignant lesions. However blood
      cultures were positive to Brucella melitensis leading to a diagnosis of hepatic
      brucelloma. CONCLUSION: Hepatic abscesses are rare in brucellosis. This infection
      has to be evoked in patients coming from endemic areas even with atypical
      manifestations.

PMID- 30220442
TI  - Morphine vs Methadone Treatment for Infants with Neonatal Abstinence Syndrome.
AB  - OBJECTIVE: To estimate the relationship of initial pharmacotherapy with methadone
      or morphine and length of stay (LOS) in infants with neonatal abstinence syndrome
      (NAS) admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: From the
      Pediatrix Clinical Data Warehouse database, we identified all infants born at
      >=36 weeks of gestation between 2011 and 2015 who were diagnosed with NAS
      (International Classification of Diseases, Ninth Revision code 779.5) and treated
      with methadone or morphine in the first 7 days of life. We used multivariable Cox
      proportional hazards regression analysis to quantify the association between
      initial treatment and LOS after adjusting for maternal age, maternal
      race/ethnicity, maternal drug use, maternal smoking, gestational age, small for
      gestational age status, inborn status, and discharge year. RESULTS: We identified
      a total of 7667 eligible infants, including 1187 treated with methadone (15%) and
      6480 treated with morphine (85%). Birth weight, gestational age, and sex were
      similar in the 2 groups. Methadone treatment was associated with a 22% shorter
      median LOS (18 days [IQR, 11-30 days] vs 23 days [IQR, 16-33]; P < .001) and a
      19% shorter median NICU stay (17 days [IQR, 10-29 days] vs 21 days [IQR, 14-36
      days]; P < .001). After adjustment, methadone was associated with a shorter LOS
      (hazard ratio for discharge, 1.24; 95% CI, 1.11-1.37; P < .001) CONCLUSION: Among
      infants born at >=36 weeks of gestation with NAS, initial methadone treatment was
      associated with a shorter LOS compared with morphine treatment. Future
      prospective comparative effectiveness trials to treat infants with NAS are needed
      to verify this observation.

PMID- 30220443
TI  - Adverse Childhood Experiences Are Associated with Unmet Healthcare Needs among
      Children with Autism Spectrum Disorder.
AB  - OBJECTIVE: To explore associations between level of adverse childhood experiences
      (ACEs) and unmet healthcare needs among children with autism spectrum disorder
      (ASD) using a population-based sample. STUDY DESIGN: Cross-sectional data from
      the 2011-2012 National Survey of Child Health were analyzed to estimate
      prevalence of unmet healthcare needs among children with ASD, aged 2-17 years
      (ASD = 1624; estimated population = 1 174 871). Multivariate Poisson and logistic
      regression models were used to estimate the relationship between reported ACEs
      and unmet healthcare needs among children with ASD. RESULTS: After we adjusted
      for all other variables, children with ASD who experienced 1-2 ACEs and 3+ ACEs
      were associated with 1.78 (P < .05) and 2.53 (P < .01) times the incidence rate
      of unmet healthcare needs in comparison with children without ACEs. Compared with
      children who experienced 0 ACEs, the adjusted odds of any unmet healthcare need
      were 2.34 (P < .01) and 2.66 (P < .01) for children with 1-2 ACEs and 3 + ACEs,
      respectively. CONCLUSION: Although limited to cross-sectional data, our study
      provides compelling evidence on the link between ACEs and unmet healthcare needs
      among children with ASD. It advances understanding of risk factors in the child
      and community context that contribute to health disparities and negatively impact
      healthcare access and use in this population.

PMID- 30220444
TI  - National registry of patients with Fukuyama congenital muscular dystrophy in
      Japan.
AB  - Fukuyama congenital muscular dystrophy (FCMD) is the second most common form of
      muscular dystrophy in the Japanese population and is caused by mutations in the
      fukutin (FKTN) gene. In 2011, the Japan Muscular Dystrophy Association (JMDA)
      developed a nationwide registry of genetically confirmed patients with FCMD. We
      retrospectively reviewed the registry dataset of patients with FCMD to obtain
      data, including age, sex, developmental milestones, intellectual level,
      complications, and primary treatments. In total, 207 patients with FCMD (104 boys
      and 103 girls) were registered by the end of September 2013. Mean patient age at
      first registration was 8.1 +/- 7.8 years (median, 6 years; range, 0-42 years). A
      homozygous 3-kb founder insertion mutation in the FKTN gene was present in 80% of
      registrants, whereas 20% had a compound heterozygous mutation. Sixty-nine
      patients (33%) had febrile seizures and/or epilepsy. Myopia was the most
      frequently detected abnormality (8.7%), followed by strabismus (5.9%). Overall,
      16% of patients required respiratory support and this percentage increased with
      age. Cardiac dysfunction was detected in 16%, and dysphagia was observed in 22%
      of patients with FCMD. The FCMD patient registry is useful for clarifying the
      natural history of FCMD and recruiting patients for clinical trials.

PMID- 30220445
TI  - New Insights into Measles Virus Brain Infections.
AB  - Measles virus (MeV) may persist in the brain, causing fatal neurodegenerative
      diseases, subacute sclerosing panencephalitis, and measles inclusion-body
      encephalitis. However, the mechanism of MeV propagation in the brain remains
      unexplained because human neurons affected by the diseases do not express the
      known receptors for MeV. Recent studies have revealed that certain changes in the
      ectodomain of the MeV fusion (F) protein play a key role in MeV spread in the
      brain. These changes destabilize the prefusion form of the F protein and render
      it hyperfusogenic, which in turn allows the virus to propagate in neurons. Based
      on crystal structures of the F protein, effective fusion inhibitors could be
      developed to treat these diseases.

PMID- 30220446
TI  - Gentamicin drug monitoring for peritonitis patients by using a CMOS-BioMEMS-based
      microcantilever sensor.
AB  - We developed a Complementary Metal-Oxide-Semiconductor Bio-Microelectromechanical
      Systems (CMOS-BioMEMS) based piezoresistive microcantilever sensor for detecting
      gentamicin, a peritonitis therapeutic small-molecule drug. In recent years, the
      patient-centric concept has been emphasized. In such a trend, therapeutic drug
      monitoring (TDM) is especially crucial for patients with peritonitis to avoid
      adverse reactions from a high concentration of gentamicin in the blood. With the
      aid of a commercialized semiconductor manufacturing process, the microcantilever
      sensing platform can serve as a portable, low-cost device and offer real-time
      detection. With chemical surface modification and capture antibody
      immobilization, the sensor can detect the small-molecule (< 2 kDa) gentamicin
      directly. We also modified the pH value of the buffer solution and applied an
      external electric field to promote sensor sensitivity. Comparing the change of
      the signals in a non-electric field of antibody immobilization and a 60-volt
      electric field of antibody immobilization showed that the average signal response
      increased 1.8 times. In the detection of gentamicin with different concentrations
      of 10-200 MUg/mL, the limit of detection (LOD) of the sensor was 9.44 ug/mL.
      Finally, the detecting result of a microrcantilever sensor was compared with the
      one measured by a common instrument in hospital, and the high correlation was
      expressed between them in gentamicin detection. The CMOS-BioMEMS-based
      piezoresistive microcantilever sensor has been demonstrated to have great
      potential as a point-of-care (POC) device for real-time drug concentration
      monitoring.

PMID- 30220447
TI  - [Evaluation of the nurse triage at the ophtalmology emergency department of
      Pierre-Paul-Riquet Hospital].
AB  - INTRODUCTION: The steady increase in the number of visits to the various
      emergency services combined with the decrease in medical demographics, make it
      necessary to optimize triage of patients to improve their care. The purpose of
      this study was to evaluate the pertinence of our triage questionnaire in the
      classification of ophthalmologic emergencies by severity. METHODS: We used a
      monocentric cross-sectional study. From September 5 through September 25 2017,
      858 patients who had all been seen in the ophthalmology emergency department of
      Pierre Paul Riquet Hospital of Toulouse university medical center and had
      responded to the triage nurse questionnaire were included. According to the
      symptoms presented or not by the patient, a color code was attributed (GREEN,
      ORANGE or RED) in order of increasing level of emergency. For each patient, we
      compared the severity of the final diagnosis by Base Score with the level of
      emergency established by our questionnaire. RESULTS: There were 118 "GREEN"
      patients, 606 "ORANGE" patients and 134 "RED." We were able to analyze 822
      patients. 21.65% of patients were correctly classified, 73.36% were overestimated
      (of which 87.06% by one level and 12.94% by two levels of severity), and 4.99%
      were underestimated (of which 90.24% by one level and 9.76% by two levels).
      CONCLUSION: Our current triage questionnaire is not sufficiently discriminating
      for effective triage of ophthalmologic emergencies. It often overestimates minor
      emergencies, causing a delay in treating other emergencies. We propose a new
      questionnaire modified according to the results obtained during our study.

PMID- 30220448
TI  - [Tuberculosis and the eye in Belgium: Report of 3 cases].

PMID- 30220449
TI  - Current state of apheresis technology and its applications.
AB  - Apheresis is at the forefront of therapeutic approaches for an increasing number
      of indications caused by formation of pathologic antibodies treated by
      therapeutic plasma exchange, or through the use of red cell exchanges to overcome
      complications secondary to sickle cell crises. Likewise, the number of
      hematopoietic stem cell transplants has continued to grow annually and this is
      the direct result of the expansion of apheresis collections. Over the years a
      number of apheresis platforms have been utilized, but as one of the oldest and
      most widely used systems, the COBE Spectra, has ceased to be used therapeutically
      and at blood centers for donations there is an active search to find suitable
      systems that will replace it and have the versatility to perform as many
      procedures as possible. Computer innovations have made it possible with current
      apheresis technology to obtain more real-time information of the procedure which
      permits the operator to adjust parameters not only to optimize the specific
      procedure but also to safeguard against potential adverse events. The focus of
      this review is to go over available clinical data describing the operation,
      outcomes and applications of apheresis platforms, and discuss those systems that
      are likely to meet clinical demands and those of blood donation centers.

PMID- 30220450
TI  - Reflections on the dynamics of bacterial and viral contamination of blood
      components and the levels of efficacy for pathogen inactivation processes.
AB  - Blood transfusion safety has been increasingly improving during the past two
      decades. However, threats from both known and emerging pathogens require
      continual improvement and re-assessment of blood safety measures. In this
      respect, we are currently witnessing the broader implementation of Pathogen
      reduction technology (PRT) for blood complements. These methods, combined with
      existing safety measures, have helped to reduce the pathogen risks of transfusion
      transmitted infections. Currently multiple reviews have compared levels of
      inactivation between different commercialized PRTs. However, to analyze levels of
      pathogen inactivation, it is necessary to understand the dynamics of infectivity
      as well as the modes of disease transmission by blood transfusion for various
      pathogens. It is well known that contributing variables include donor
      characteristics through the processing of blood components to ultimately the
      recipient characteristics, which create enormous variability in overall outcomes
      relative to disease transmission. The aim of this paper is to discuss bacterial
      and viral contamination of blood components in order to determine adequate levels
      of efficacy and subsequent disease transmission safety of current pathogen
      inactivation protocols that are designed to reduce the risk of transfusion
      transmitted infections. In such a conceptual analysis, however, it is important
      to understand several contributing factors including the measurement of pathogen
      load in blood products and the dynamics, infectivity and disease transmission of
      various pathogens via transfusion of blood components and products. In many
      cases, the log reduction values observed do not truly reflect the extent of
      reduction in the levels of infectivity that are observed clinically. Results from
      clinical trials and hemovigilance programs upon routine implementation of PRT
      methods provide a more direct insight into effectiveness with regard to clinical
      relevance of in vitro spiking studies. These issues are briefly addressed in this
      manuscript.

PMID- 30220451
TI  - Surgical repair of long-gap esophageal atresia: A retrospective study comparing
      the management of long-gap esophageal atresia in the Nordic countries.
AB  - BACKGROUND: Several surgical procedures have been described in the reconstruction
      of long-gap esophageal atresia (LGEA). We reviewed the surgical methods used in
      children with LGEA in the Nordic countries over a 15-year period and the
      postoperative complications within the first postoperative year. METHODS:
      Retrospective multicenter medical record review of all children born with Gross
      type A or B esophageal atresia between 01/01/2000 and 12/31/2014 reconstructed
      within their first year of life. RESULTS: We included 71 children; 56 had Gross
      type A and 15 type B LGEA. Delayed primary anastomosis (DPA) was performed in
      52.1% and an esophageal replacement procedure in 47.9%. Gastric pull-up (GPU) was
      the most frequent procedure (25.4%). The frequency of chromosomal abnormalities,
      congenital heart defects and other anomalies was significantly higher in patients
      who had a replacement procedure. The frequency of gastroesophageal reflux (GER)
      was significantly higher after DPA compared to esophageal replacement (p =
      0.013). At 1-year follow-up the mean body weight was higher after DPA than after
      organ interposition (p = 0.043). CONCLUSION: DPA and esophageal replacement
      procedures were equally applied. Postoperative complications and follow-up were
      similar except for the development of GER and the body weight at 1-year follow
      up. Long-term results should be investigated. TYPE OF STUDY: Treatment study.
      LEVEL OF EVIDENCE: Level III.

PMID- 30220452
TI  - Ovarian masses in the child and adolescent: An American Pediatric Surgical
      Association Outcomes and Evidence-Based Practice Committee systematic review.
AB  - BACKGROUND: The treatment of ovarian masses in pediatric patients should balance
      appropriate surgical management with the preservation of future reproductive
      capability. Preoperative estimation of malignant potential is essential to
      planning an optimal surgical strategy. METHODS: The American Pediatric Surgical
      Association Outcomes and Evidence-Based Practice Committee drafted three
      consensus-based questions regarding the evaluation and treatment of ovarian
      masses in pediatric patients. A search of PubMed, the Cochrane Library, and Web
      of Science was performed and Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) guidelines were followed to identify articles for review.
      RESULTS: Preoperative tumor markers, ultrasound malignancy indices, and the
      presence or absence of the ovarian crescent sign on imaging can help estimate
      malignant potential prior to surgical resection. Frozen section also plays a role
      in operative strategy. Surgical staging is useful for directing chemotherapy and
      for prognostication. Both unilateral oophorectomy and cystectomy have been used
      successfully for germ cell and borderline ovarian tumors, although cystectomy may
      be associated with higher rates of local recurrence. CONCLUSIONS: Malignant
      potential of ovarian masses can be estimated preoperatively, and fertility
      sparing techniques may be appropriate depending on the type of tumor. This review
      provides recommendations based on a critical evaluation of recent literature.
      TYPE OF STUDY: Systematic review of level 1-4 studies. LEVEL OF EVIDENCE: Level 1
      4 (mainly 3-4).

PMID- 30220453
TI  - Angioedema and emergency medicine: From pathophysiology to diagnosis and
      treatment.
AB  - Angioedema is a self-limiting edema of the subcutaneous or submucosal tissues due
      to localised increase of microvascular permeability whose mediator may be
      histamine or bradykinin. Patients present to emergency department when angioedema
      involves oral cavity and larynx (life-threatening conditions) or gut (mimicking
      an acute abdomen). After initial evaluation of consciousness and vital signs to
      manage breathing and to support circulation if necessary, a simple approach can
      be applied for a correct diagnosis and treatment. Forms of edema such as
      anasarca, myxedema, superior vena cava syndrome and acute dermatitis should be
      ruled out. Then, effort should be done to differentiate histaminergic from non
      histaminergic angioedema. Concomitant urticaria and pruritus suggest a
      histaminergic origin. Exposure to allergens and drugs (mainly ACE inhibitors and
      non steroidal anti-inflammatory drugs) should be investigated as well as a family
      history of similar symptoms. Allergic histaminergic angioedema has a rapid course
      (minutes) whereas non histaminergic angioedema is slower (hours). Since
      frequently the intervention needs to be immediate, the initial diagnosis is only
      clinical. However, laboratory tests can be subsequently confirmatory. Allergic
      angioedema is sensitive to standard therapies such as epinephrine,
      glucocorticoids and antihistamines whereas non histaminergic angioedema is often
      resistant to these drugs. Therapeutic options for angioedema due C1-inhibitor
      deficiencies are C1-inhibitor concentrates, icatibant and ecallantide. If these
      drugs are not available, fresh frozen plasma can be considered. All these
      medications have been used also in ACE inhibitor-induced angioedema with variable
      results thus they are not currently recommended whereas experts agree on the
      discontinuation of the causative drug.

PMID- 30220455
TI  - C. elegans AWA Olfactory Neurons Fire Calcium-Mediated All-or-None Action
      Potentials.
AB  - Neurons in Caenorhabditis elegans and other nematodes have been thought to lack
      classical action potentials. Unexpectedly, we observe membrane potential spikes
      with defining characteristics of action potentials in C. elegans AWA olfactory
      neurons recorded under current-clamp conditions. Ion substitution experiments,
      mutant analysis, pharmacology, and modeling indicate that AWA fires calcium
      spikes, which are initiated by EGL-19 voltage-gated CaV1 calcium channels and
      terminated by SHK-1 Shaker-type potassium channels. AWA action potentials result
      in characteristic signals in calcium imaging experiments. These calcium signals
      are also observed when intact animals are exposed to odors, suggesting that
      natural odor stimuli induce AWA spiking. The stimuli that elicit action
      potentials match AWA's specialized function in climbing odor gradients. Our
      results provide evidence that C. elegans neurons can encode information through
      regenerative all-or-none action potentials, expand the computational repertoire
      of its nervous system, and inform future modeling of its neural coding and
      network dynamics.

PMID- 30220454
TI  - ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P.
AB  - Nonalcoholic fatty liver disease (NAFLD) progresses to nonalcoholic
      steatohepatitis (NASH) in response to elevated endoplasmic reticulum (ER) stress.
      Whereas the onset of simple steatosis requires elevated de novo lipogenesis,
      progression to NASH is triggered by accumulation of hepatocyte-free cholesterol.
      We now show that caspase-2, whose expression is ER-stress inducible and elevated
      in human and mouse NASH, controls the buildup of hepatic-free cholesterol and
      triglycerides by activating sterol regulatory element-binding proteins (SREBP) in
      a manner refractory to feedback inhibition. Caspase-2 colocalizes with site 1
      protease (S1P) and cleaves it to generate a soluble active fragment that
      initiates SCAP-independent SREBP1/2 activation in the ER. Caspase-2 ablation or
      pharmacological inhibition prevents diet-induced steatosis and NASH progression
      in ER-stress-prone mice. Caspase-2 inhibition offers a specific and effective
      strategy for preventing or treating stress-driven fatty liver diseases, whereas
      caspase-2-generated S1P proteolytic fragments, which enter the secretory pathway,
      are potential NASH biomarkers.

PMID- 30220456
TI  - A Bacterial Chromosome Structuring Protein Binds Overtwisted DNA to Stimulate
      Type II Topoisomerases and Enable DNA Replication.
AB  - When DNA is unwound during replication, it becomes overtwisted and forms positive
      supercoils in front of the translocating DNA polymerase. Unless removed or
      dissipated, this superhelical tension can impede replication elongation.
      Topoisomerases, including gyrase and topoisomerase IV in bacteria, are required
      to relax positive supercoils ahead of DNA polymerase but may not be sufficient
      for replication. Here, we find that GapR, a chromosome structuring protein in
      Caulobacter crescentus, is required to complete DNA replication. GapR associates
      in vivo with positively supercoiled chromosomal DNA, and our biochemical and
      structural studies demonstrate that GapR forms a dimer-of-dimers that fully
      encircles overtwisted DNA. Further, we show that GapR stimulates gyrase and topo
      IV to relax positive supercoils, thereby enabling DNA replication. Analogous
      chromosome structuring proteins that locate to the overtwisted DNA in front of
      replication forks may be present in other organisms, similarly helping to recruit
      and stimulate topoisomerases during DNA replication.

PMID- 30220457
TI  - Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid
      Tumors.
AB  - Mutations or aberrant upregulation of EZH2 occur frequently in human cancers, yet
      clinical benefits of EZH2 inhibitor (EZH2i) remain unsatisfactory and limited to
      certain hematological malignancies. We profile global posttranslational histone
      modification changes across a large panel of cancer cell lines with various
      sensitivities to EZH2i. We report here oncogenic transcriptional reprogramming
      mediated by MLL1's interaction with the p300/CBP complex, which directs H3K27me
      loss to reciprocal H3K27ac gain and restricts EZH2i response. Concurrent
      inhibition of H3K27me and H3K27ac results in transcriptional repression and MAPK
      pathway dependency in cancer subsets. In preclinical models encompassing a broad
      spectrum of EZH2-aberrant solid tumors, a combination of EZH2 and BRD4
      inhibitors, or a triple-combination including MAPK inhibition display robust
      efficacy with very tolerable toxicity. Our results suggest an attractive
      precision treatment strategy for EZH2-aberrant tumors on the basis of tumor
      intrinsic MLL1 expression and concurrent inhibition of epigenetic crosstalk and
      feedback MAPK activation.

PMID- 30220458
TI  - An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney
      Fibrosis.
AB  - The occurrence of a spontaneous nephropathy with intranuclear inclusions in
      laboratory mice has puzzled pathologists for over 4 decades, because its etiology
      remains elusive. The condition is more severe in immunodeficient animals,
      suggesting an infectious cause. Using metagenomics, we identify the causative
      agent as an atypical virus, termed "mouse kidney parvovirus" (MKPV), belonging to
      a divergent genus of Parvoviridae. MKPV was identified in animal facilities in
      Australia and North America, is transmitted via a fecal-oral or urinary-oral
      route, and is controlled by the adaptive immune system. Detailed analysis of the
      clinical course and histopathological features demonstrated a stepwise
      progression of pathology ranging from sporadic tubular inclusions to tubular
      degeneration and interstitial fibrosis and culminating in renal failure. In
      summary, we identify a widely distributed pathogen in laboratory mice and
      establish MKPV-induced nephropathy as a new tool for elucidating mechanisms of
      tubulointerstitial fibrosis that shares molecular features with chronic kidney
      disease in humans.

PMID- 30220459
TI  - Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and
      Redox Homeostasis in Glioma.
AB  - IDH1 mutations are common in low-grade gliomas and secondary glioblastomas and
      cause overproduction of (R)-2HG. (R)-2HG modulates the activity of many enzymes,
      including some that are linked to transformation and some that are probably
      bystanders. Although prior work on (R)-2HG targets focused on 2OG-dependent
      dioxygenases, we found that (R)-2HG potently inhibits the 2OG-dependent
      transaminases BCAT1 and BCAT2, likely as a bystander effect, thereby decreasing
      glutamate levels and increasing dependence on glutaminase for the biosynthesis of
      glutamate and one of its products, glutathione. Inhibiting glutaminase
      specifically sensitized IDH mutant glioma cells to oxidative stress in vitro and
      to radiation in vitro and in vivo. These findings highlight the complementary
      roles for BCATs and glutaminase in glutamate biosynthesis, explain the
      sensitivity of IDH mutant cells to glutaminase inhibitors, and suggest a strategy
      for maximizing the effectiveness of such inhibitors against IDH mutant gliomas.

PMID- 30220461
TI  - Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol
      Transport in Mammalian Cells.
AB  - The mechanisms underlying sterol transport in mammalian cells are poorly
      understood. In particular, how cholesterol internalized from HDL is made
      available to the cell for storage or modification is unknown. Here, we describe
      three ER-resident proteins (Aster-A, -B, -C) that bind cholesterol and facilitate
      its removal from the plasma membrane. The crystal structure of the central domain
      of Aster-A broadly resembles the sterol-binding fold of mammalian StARD proteins,
      but sequence differences in the Aster pocket result in a distinct mode of ligand
      binding. The Aster N-terminal GRAM domain binds phosphatidylserine and mediates
      Aster recruitment to plasma membrane-ER contact sites in response to cholesterol
      accumulation in the plasma membrane. Mice lacking Aster-B are deficient in
      adrenal cholesterol ester storage and steroidogenesis because of an inability to
      transport cholesterol from SR-BI to the ER. These findings identify a
      nonvesicular pathway for plasma membrane to ER sterol trafficking in mammals.

PMID- 30220460
TI  - A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission.
AB  - Endoplasmic reticulum (ER) membrane contact sites (MCSs) mark positions where
      endosomes undergo fission for cargo sorting. To define the role of ER at this
      unique MCS, we targeted a promiscuous biotin ligase to cargo-sorting domains on
      endosome buds. This strategy identified the ER membrane protein TMCC1, a member
      of a conserved protein family. TMCC1 concentrates at the ER-endosome MCSs that
      are spatially and temporally linked to endosome fission. When TMCC1 is depleted,
      endosome morphology is normal, buds still form, but ER-associated bud fission and
      subsequent cargo sorting to the Golgi are impaired. We find that the endosome
      localized actin regulator Coronin 1C is required for ER-associated fission of
      actin-dependent cargo-sorting domains. Coronin 1C is recruited to endosome buds
      independently of TMCC1, while TMCC1/ER recruitment requires Coronin 1C. This link
      between TMCC1 and Coronin 1C suggests that the timing of TMCC1-dependent ER
      recruitment is tightly regulated to occur after cargo has been properly
      sequestered into the bud.

PMID- 30220462
TI  - Design, display and immunogenicity of HIV1 gp120 fragment immunogens on virus
      like particles.
AB  - The broadly neutralizing antibody against HIV-1, b12, binds to the CD4 binding
      site (CD4bs) on the outer domain (OD) of the gp120 subunit of HIV-1 Env. We have
      previously reported the design of an E. coli expressed fragment of HIV-1 gp120,
      b122a, containing about 70% of the b12 epitope with the idea of focusing the
      immune response to this structure. Since the b122a structure was found to be only
      partially folded, as assessed by circular dichroism and protease resistance, we
      attempted to stabilize it by the introduction of additional disulfide bonds. One
      such mutant, b122a1-b showed increased stability and bound b12 with 30-fold
      greater affinity as compared to b122a. Various b122a and OD fragment proteins
      were displayed on the surface of Qbeta virus-like particles. Sera raised against
      these particles in six-month long rabbit immunization studies could neutralize
      Tier1 viruses across different subtypes with the best results observed with
      b122a1-b displayed particles. Significantly higher amounts of antibodies directed
      towards the CD4bs were also elicited by particles displaying b122a1-b. This study
      highlights the ability of fragment immunogens to focus the antibody response to
      the conserved CD4bs of HIV-1.

PMID- 30220463
TI  - Hemophagocytic lymphohistiocytosis associated with an IgG Cold agglutinin.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease eventually
      caused or reactivated by a viral infection, which can also lead to the production
      of cold agglutinins (CA). The nature of these autoantibodies is usually an IgM,
      less frequently an IgA or IgG, they agglutinate red blood cells at low
      temperatures. They can interfere with hematological parameters causing
      interpretation difficulties. We report a case of a 4-year-old boy who developed
      an IgG CA during recurrent HLH reactivated by EBV infection. The purpose of this
      observation is to underline HLH criteria and to analyze CA interference as well
      as its biological and clinical characteristics.

PMID- 30220464
TI  - Influence of puffing conditions on the carbonyl composition of e-cigarette
      aerosols.
AB  - Owing to their harmful effects on human health, the presence of carbonyl
      compounds in e-cigarette aerosols raises concerns. To date, the reported
      concentration levels in e-vapors vary greatly between studies and several factors
      that markedly influence carbonyl emission during vaping have been highlighted
      including the heating temperature, the power supply, the device architecture, the
      filling level of the tank and the main e-liquid constituents. This study
      investigated the impact of puffing regimen parameters on the carbonyl composition
      of e-cigarette aerosols with the aim of: (1) better estimating the variability of
      carbonyl emissions depending on puffing conditions; (2) highlighting puffing
      profiles that increase the exposure to carbonyls; and (3) estimating to what
      extent puffing topography could be implied in the variability of carbonyl
      concentrations reported in the current literature. E-vapors from a single e
      liquid were generated from two e-cigarette models with a smoking machine. A total
      of 7 different puffing regimens were used to individually study the influence of
      the puff volume, duration and frequency. Carbonyls were collected by DNPH
      cartridges and analysed by HPLC-UV. E-liquid consumption and e-vapor temperature
      were also monitored. E-vapor concentrations of formaldehyde, acetaldehyde,
      acetone, acrolein, propionaldehyde and methylglyoxal were affected, sometimes
      differently, by the modification of the puffing regimen, as well as by the e
      cigarette model. For example, formaldehyde concentration ranged from 20 to 255
      ng/puff depending on the puffing conditions. The results of principal component
      analyses, applied to the concentration data sets for the 6 carbonyls, suggest
      that the studied parameters interact and highlight some "carbonyl-emitting"
      combinations of concern (e-cigarette model/puffing regimen). However, the highest
      concentrations measured in the present study remain far lower than those observed
      in conventional cigarette mainstream smoke. This study confirms that the chosen
      puffing regimen contributes a part of the observed variability in the carbonyl
      levels reported in the scientific literature, hampering comparisons between
      studies and making interpretation difficult. Thus, harmonized and realistic
      protocols for the assessment of e-cigarette toxicity by physicochemical or
      experimental approaches are clearly needed.

PMID- 30220465
TI  - Abscense of survival benefit of immediate lymph node dissection in melanoma.

PMID- 30220466
TI  - Relationship of the presence of insomnia with walking physical activity and diet
      quality: A cross-sectional study in a sample of Spanish adults.
AB  - INTRODUCTION AND OBJECTIVES: Certain lifestyle habits may influence aspects of
      sleep quality, such as insomnia. The main objective of the present study was to
      analyze the relationship of the presence of insomnia, with walking physical
      activity and diet quality in an adult population. PATIENTS AND METHODS: A cross
      sectional descriptive study was performed (subanalysis of the TRIPLE A study)
      between January of 2014 to June of 2015. A total of 454 subjects were selected by
      consecutive sampling. Insomnia was evaluated with the Atenas scale, diet quality
      using the diet quality index (DQI) questionnaire, and physical activity using
      pedometers for seven days, evaluating the total number of steps, aerobic steps,
      and energy expended. RESULTS: Of all patients, 26.8% presented with insomnia
      (33.8% in women and 17.5% in men). In a adjusted model, the mean differences of
      total steps/day, aerobic steps/day, and kilocalories/day spent in performing
      physical activity, between no insomnia group and insomnia group were: 1022.5 (95%
      CI: 177.9-1867.0), 743.9 (95% CI: 68.3-1419.4) and 39.8 (95% CI: 5.7-73.9),
      respectively. We did not find an association between the diet quality index (DQI)
      and insomnia. CONCLUSIONS: The findings suggest that completing daily a greater
      total number of steps, aerobic steps, and energy expended by walking, could be
      correlated with less insomnia, independent of age, sex, and other confounding
      variables. However, no relationship was observed between diet quality and
      insomnia.

PMID- 30220467
TI  - Tobacco, the forgotten factor in the calculation and approach of cardiovascular
      risk.

PMID- 30220468
TI  - Massive gingival hyperplasia due to cyclosporine.

PMID- 30220469
TI  - Job syndrome.

PMID- 30220470
TI  - Prostate-specific antigen screening for prostate cancer in males older than 75
      years.

PMID- 30220471
TI  - Better Scientific Writing Does Not Need Linguistic Alchemy: Response to Doubleday
      and Connell 2017.

PMID- 30220472
TI  - Drilling for Insight: Forecasting Phenotype from Genotype.
AB  - The manifestation of disease can vary substantially from person to person. Yet,
      much of the emphasis of genomics in individualized medicine has been on linking
      genetic variants to broad disease categories. A new approach takes a first step
      towards predicting detailed phenotypic information from disease-causative
      variants.

PMID- 30220473
TI  - [Clinical and morphological indications for delayed breast reconstruction].
AB  - A full range of breast reconstructions procedures exists and had to be proposed
      within a surgical team, from the simplest to the most complex. The choice of the
      technique is simply based on the discussion between the surgeon and the patient
      during a consultation. A computed tomographic angiography might be required in
      the case of DIEP flap reconstruction. The surgeon bases his decision on a
      clinical exam of the breast area, the quality of the tissues and looks for
      potential flaps or fat donor sites. The patient expresses her expectations in
      terms of breast volume, form and is clearly informed about potential risks and
      follow-up. Thus the surgeon could propose the most adequate procedure in the case
      of the patient, who will take the final decision. The surgeon should ensure to
      find the most adapted procedure to each individual. A well-determined indication
      will lead to a truly satisfied patient, which is the main goal of breast
      reconstruction. We decided to present this dialogue and the path towards the
      final choice in a fun and original format.

PMID- 30220474
TI  - [History of breast cancer reconstruction treatment].
AB  - The authors summarize in those six pages of drawings the history of breast cancer
      reconstruction treatment. The focus is on the variety of techniques available for
      breast reconstruction and on the debates around different indications.

PMID- 30220475
TI  - The Family-Resemblances Framework for Mind-Wandering Remains Well Clad.

PMID- 30220476
TI  - Mind-Wandering as a Scientific Concept: Cutting through the Definitional Haze.

PMID- 30220477
TI  - Laparoscopic treatment of type II Mirizzi Syndrome with common bile duct plasty.

PMID- 30220478
TI  - Life expectancy in pancreatic neuroendocrine cancer.
AB  - BACKGROUND: The prognoses widely reported for pancreatic cancer reflect the very
      poor survival associated with the most common histological type, exocrine
      adenocarcinoma. We calculated life expectancies for patients with less common
      pancreatic neuroendocrine tumors (PNETs), and also for the subsets of these
      patients who survive 1 and 5 years post-diagnosis, all of which carry a
      significantly better prognosis. Results for 1- and 5-year PNET survivors appear
      not to have been previously reported, nor have life expectancies (average long
      term survival times) been given. METHODS: We identified 5287 cases of PNET in the
      SEER US national database, 1973-2013. The Kaplan-Meier estimator was used to
      compute empirical survival probabilities and median survival times for
      functioning (n = 279) and non-functioning PNET (n = 5008) cases. The Cox
      proportional hazards regression model was used to examine univariate associations
      of survival with covariates including patient age, sex, race, cancer stage, tumor
      grade, surgical treatment, and calendar year. A multivariate multiplicative
      hazard Poisson regression model estimated mortality rates for all combinations of
      the covariates. The rates were used to construct actuarial life tables, which
      gave life expectancies for male and female patients according to age, cancer
      stage, tumor grade, histology (functioning versus non-functioning), surgical
      treatment status, and time since diagnosis. These life expectancies were compared
      with age- and sex-specific figures from the US general population. RESULTS: Life
      expectancy in PNET is lower than that of the US general population and varies
      significantly according to patient age, cancer stage, tumor grade, mode of
      treatment, and time since diagnosis. For example, it is near normal for persons
      aged 70 and older who undergo surgical resection of localized well-differentiated
      (i.e., grade I) tumors. By contrast, persons with metastatic high-grade tumors
      not amenable to surgery have life expectancies of only 1 to 4 years depending on
      patient age. Functioning PNETs were associated with somewhat lower mortality than
      non-functioning within the first few years after diagnosis, though no major
      differences were observed long-term. Positive factors for survival were younger
      age, localized stage, low tumor grade, and surgical treatment. Survival improved
      over the 1973-2013 study period: on average mortality rates fell by 1.2% per year
      after controlling for changes in the patient population. Life expectancy
      increased markedly with time since diagnosis: those surviving 1 and 5 years post
      diagnosis had longer additional life expectancies. CONCLUSIONS: Life expectancies
      of patients with PNETs may be markedly reduced from normal, but even in the worst
      cases their prognoses remain significantly better than that of patients with the
      more common pancreatic adenocarcinomas. In some very favorable cases, the life
      expectancy is near-normal, especially amongst 1- and 5-year survivors. This
      information can be used to counsel patients.

PMID- 30220479
TI  - Sialendoscopy under conscious sedation versus general anesthesia. A comparative
      study.
AB  - OBJECTIVE: Sialendoscopy is a minimally invasive emerging approach, the general
      surgical technique has been published but many essential questions still need to
      be addressed with the aim of improving outcomes. For instance, should we
      systematically perform sialendoscopy under conscious sedation (CS) or general
      anesthesia (GA)? What are the limitations of CS? The objective of this study is
      to compare these two modalities. METHODOLOGY: A retrospective study of 70
      patients who had undergone a sialendoscopy between 2014 and 2016 (34 under GA and
      36 under CS). Comparisons were made between these two groups in term of operative
      time, stone size and location, tolerability, operative success and post-operative
      pain. RESULT: The patients' mean age was 45.33 years. The operative success rate
      among the GA group was 79.4% vs. 88.9% in the CS group (P = 0.276), while
      complications for both groups were comparable. All patients considered the
      intervention under CS to be tolerable. CONCLUSION: Sialendoscopy under CS or GA
      demonstrated the ability to access large and distal stones among the different
      salivary glands with an excellent tolerability. Anesthesia type should be based
      on surgeon and patient preference Nevertheless, patient reassurance and surgeon
      experience are important to producing a good result with CS.

PMID- 30220480
TI  - Development of Quality Indicators for Cardiac Rehabilitation in Australia: A
      Modified Delphi Method and Pilot Test.
AB  - BACKGROUND: International guidelines recommend cardiac rehabilitation (CR) for
      secondary prevention of cardiovascular disease, however, it is underutilised and
      the quality of content and delivery varies widely. Quality indicators (QIs) for
      CR are used internationally to measure clinical practice performance, but are
      lacking in the Australian context. This study reports the development of QIs for
      minimum dataset (MDS) for CR and the results of a pilot test for feasibility and
      applicability in clinical practice in Australia. METHODS: A modified Delphi
      method was used to develop initial QIs which involved a consensus approach
      through a series of face-to-face and teleconference meetings of an expert
      multidisciplinary panel (n=8), supplemented by an environmental scan of the
      literature and a multi-site pilot test. RESULTS: Eight QIs were proposed and sent
      to CR clinicians (n=250) electronically to rate importance, current data
      collection status, and feasibility of future collection. The top six of these QIs
      were selected with an additional two key performance indicators from the New
      South Wales (NSW) Ministry of Health and two QIs from international registers for
      a draft MDS. The pilot test in 16 sites (938 patient cases) demonstrated median
      performance of 93% (IQR 47.1-100%). All 10 QIs were retained and one further QI
      related to diabetes was added for a final draft MDS. CONCLUSIONS: The MDS of 11
      QIs for CR provides an important foundation for collection of data to promote the
      quality of CR nationally and the opportunity to participate in international
      benchmarking.

PMID- 30220481
TI  - Human Epicardial Adipose Tissue Activin A Expression Predicts Occurrence of
      Postoperative Atrial Fibrillation in Patients Receiving Cardiac Surgery.
AB  - BACKGROUND: Activin A secreted by epicardial adipose tissue (EAT) plays a major
      role in the progress of atrial fibrosis. However, the potential of Activin A in
      predicting the occurrence of postoperative AF (POAF) has yet to be elucidated. We
      aimed to investigate the predicable value of Activin A expression in EAT on POAF.
      METHODS: A total of 89 patients receiving cardiac surgery without atrial
      fibrillation (AF) history were enrolled in this study, including 49 patients with
      valvular heart disease (VHD) and 40 patients with non-valvular heart disease
      (NVHD). Activin A expression in EAT was determined by quantitative polymerase
      chain reaction (qPCR), while the thickness of EAT (EATT) was estimated by
      echocardiography. New onset POAF before discharge was documented. RESULTS:
      Eventually 32 patients (36.0%) developed POAF, including 20 patients with VHD
      (40.8%) and 12 patients with NVHD (30.0%). Activin A expression was higher in
      POAF than sinus rhythm (SR) patients, whether for VHD or NVHD group (All
      p<0.001). In general, Activin A expression predicted the occurrence of POAF with
      a sensitivity of 65.6% and specificity of 91.2% (AUC: 0.795; 95%CI: 0.693-0.897,
      p<0.001). Subgroup analysis showed that EATT was not significant for the VHD
      group in predicting POAF (p=0.07), while Activin A expression demonstrated a
      sensitivity of 60.0% and specificity of 89.7% (AUC: 0.745; 95%CI: 0.601-0.889,
      p<0.001). Multivariate regression analysis showed that Activin A expression in
      EAT was an independent risk factor for POAF (OR: OR=1.067, 95%CI:1.002-1.136,
      p=0.042). CONCLUSIONS: Activin A expression in EAT is an independent risk factor
      for POAF, which can be used for prediction of POAF, especially for patients with
      VHD.

PMID- 30220482
TI  - Stroke Risk Stratification: CHA2DS2-VA or CHA2DS2-VASc?

PMID- 30220483
TI  - Combining Salmonella Dublin genome information and contact-tracing to
      substantiate a new approach for improved detection of infectious transmission
      routes in cattle populations.
AB  - This study presents a new method for detection of between-herd livestock
      movements to facilitate disease tracing and more accurately describe network
      behaviour of relevance for spread of infectious diseases, including within
      livestock business risk-carrying contacts that are not necessarily recorded
      anywhere. The study introduces and substantiates the concept of grouping
      livestock herds into business-units based on ownership and location in the
      tracing analysis of animal movement-based contact networks. To test the utility
      of this approach, whole core genome sequencing of 196 Salmonella Dublin isolates
      stored from previous surveillance and project activities was combined with
      information on cattle movements recorded in the Danish Cattle Database between
      1997 and 2017. The aim was to investigate alternative explanations for S. Dublin
      circulation in groups of herds connected by ownership, but without complete
      records of livestock movements. The EpiContactTrace R-package was used to trace
      the contact networks between businesses and compare the network characteristics
      of businesses sharing strains of S. Dublin with different levels of genetic
      relatedness. The ownership-only definition proved to be an unreliable grouping
      approach for large businesses, which could have internal distances larger than
      250 km and therefore do not represent useful epidemiological units. Therefore,
      the grouping was refined using spatial analysis. More than 90% of final business
      units formed were composed of one single cattle property, whereas multi-property
      businesses could reach up to eight properties in a given year, with up to 15
      cattle herds having been part of the same business through the study period.
      Results showed markedly higher probabilities of introduction of infectious
      animals between proposed businesses from which the same clone of S. Dublin had
      been isolated, when compared to businesses with non-related strains, thus
      substantiating the business-unit as an important epidemiological feature to
      consider in contact network analysis and tracing of infection routes. However,
      this approach may overestimate real-life contacts between cattle properties and
      putatively overestimate the degree of risk-contacts within each business, since
      it is based solely on information about property ownership and location. This
      does not consider administrative and individual farmers behaviours that
      essentially keep two properties separated. Despite this, we conclude that
      defining epidemiological units based on businesses is a promising approach for
      future disease tracing tasks.

PMID- 30220484
TI  - Left-dominant arrhythmogenic cardiomyopathy diagnosed at cardiac CT.

PMID- 30220485
TI  - Does active smoking really matter before ventral hernia repair? An AHSQC
      analysis.
AB  - BACKGROUND: Many studies implicate active smoking as a risk factor for
      postoperative wound complications and all 30-day morbidity, but the definitions
      of inclusion and exclusion criteria as well as outcome parameters are
      inconsistent. Critically, the ability of large databases and meta-analyses to
      generate statistically significant associations of active smoking with morbidity
      do not address whether those relationships are actually clinically meaningful. We
      investigated this relationship after open ventral hernia repair. STUDY DESIGN:
      Patients undergoing elective open ventral hernia repair in clean wounds with 30
      day follow-up were extracted from the Americas Hernia Society Quality
      Collaborative. Current smokers (within 30 days of surgery) were 1:1 propensity
      matched to patients who had never smoked based on demographics, comorbidities,
      and operative characteristics. Wound complications and all 30-day morbidity were
      assessed. RESULTS: After matching 418 current smokers to 418 patients who had
      never smoked, the groups were similar with the exception of minor differences in
      body mass index (31.4 vs 33.3, P < .001) and incidence of chronic obstructive
      pulmonary disease (18% vs 6%, P < .001). Rates of surgical site occurrence were
      greater in active smokers (12.0% vs 7.4%, P = .03) driven by increased rates of
      wound cellulitis (2.4% vs 1.2%) and seroma (5.5% vs 1.2%); however, rates of
      surgical site infection (4.1 vs 4.1, P = .98), surgical site occurrences
      requiring a procedural intervention (6.2% vs 5.0%, P = .43), reoperation (1.9% vs
      1.2%, P = .39), and all 30-day morbidity (7.5 vs 6.6, P = .60) were not
      significantly increased in active smokers. There were no instances of mesh
      excision. CONCLUSION: Active smoking prior to elective clean OVHR is associated
      with clinically insignificant differences in wound morbidity. Surgeons allowing
      perioperative smoking should monitor their outcomes to assure these findings are
      replicable in their own practice.

PMID- 30220486
TI  - Traditional face-bow transfer versus three-dimensional virtual reconstruction in
      orthognathic surgery.
AB  - Face-bow transfer is an essential step in articulator-based orthognathic surgery
      planning. However, it can be a source of inaccuracy. Virtual computer-based
      planning avoids this error through the use of direct patient-related three
      dimensional imaging data. The aim of this prospective observational study was to
      determine the error of face-bow transfer three-dimensionally and correlate it to
      the different types of malocclusion. Orthognathic surgery performed on 38
      patients (10 male, 28 female; mean (standard deviation) age 24.7 (6.9) years) was
      planned twice: first articulator-based with plaster models and second computer
      based with surgery planning software. Both models were digitized and compared
      regarding the angle between the Frankfort horizontal plane and the occlusal
      plane. In most cases, the angle in the sagittal dimension was higher in the
      articulator-based model than in the computer-based model. The angle in the
      transverse dimension was as often under- as over-represented. The type of
      malocclusion, i.e. skeletal class, vertical relationship, and degree of
      asymmetry, had no significant impact on the amount of error. In conclusion, this
      study indicates that computer-based planning should be considered as an
      advantageous alternative in orthognathic surgery planning.

PMID- 30220487
TI  - Serial block face scanning electron microscopy in cell biology: Applications and
      technology.
AB  - Three-dimensional electron microscopy (3DEM) is an imaging field containing
      several powerful modalities such as serial section transmission electron
      microscopy and electron tomography. However, large-scale 3D studies of biological
      ultrastructure on a cellular scale have historically been hampered by the
      difficulty of available techniques. Serial block face scanning electron
      microscopy (SBFSEM) is a 3DEM technique, developed in 2004, which has greatly
      increased the reliability, availability and throughput of 3DEM. SBFSEM allows for
      3D imaging at resolutions high enough to resolve membranes and small vesicles
      whilst having the capability to collect data with a large field of view. Since
      its introduction it has become a major tool for ultrastructural investigation and
      has been applied in the study of many biological fields, such as connectomics,
      cellular and matrix biology. In this review, we will discuss biological SBFSEM
      from a technical standpoint, with a focus on cellular applications and also
      subsequent image analysis techniques.

PMID- 30220488
TI  - [Interferon gamma release assay tests and nontuberculous mycobacteria].

PMID- 30220489
TI  - [Sarcoid-like granulomatosis in cancer patients treated with immune checkpoints
      inhibitors].
AB  - INTRODUCTION: Immune checkpoint inhibitors are becoming a standard treatment for
      many different cancers. Their toxicities are variable and include organ-specific
      dysimmune injuries and the development of systemic diseases. CASE REPORT: We
      report 3 cases of sarcoid-like granulomatosis that occurred during treatment of
      various types of primary cancer by immune checkpoint inhibitors: lung
      adenocarcinoma, small cell lung cancer and melanoma. The clinical presentation,
      radiologic pattern and severity of this toxicity were variable. The diagnosis was
      made on biopsy with pathological examination and exclusion of differential
      diagnoses, particularly infection. In such cases, immunotherapy should be
      discontinued and subsequent rechallenge discussed later. Systemic corticosteroids
      should be considered depending on the severity of symptoms. CONCLUSIONS:
      Knowledge of this toxicity is crucial as the clinical signs and radiological
      patterns may suggest tumour progression.

PMID- 30220490
TI  - [Near-drowning associated Aeromonas pneumonia].
AB  - INTRODUCTION: Aeromonas pneumonia associated with near-drowning, though uncommon,
      is serious and a major morbidity factor for patients. CLINICAL CASE: A healthy 30
      year-old man nearly drowned in a pound. He was admitted to the medical intensive
      care unit and required intubation and mechanical ventilation. He was given
      antibiotic therapy in the form of amoxicillin/clavulanic acid. After a brief
      stable period post immersion, he rapidly developed fever and respiratory failure.
      The thoracic scan revealed bilateral alveolar infiltrates and led to a fibreoptic
      bronchoscopy. Aeromonas veroniiandPseudomonas aeruginosa were found on culture of
      the bronchial aspirate. A change of antibiotic therapy appropriate to these
      bacteria led to clinical improvement and allowed complete withdrawal of
      ventilation. CONCLUSION: Rapid respiratory deterioration following near-drowning
      should raise the suspicion of pulmonary infection with the bacteria usually found
      in the respiratory tract during ventilation but without overlooking the
      possibility of unusual organisms, particularly Aeromonas.It is usuallysensitive
      to third generation cephalosporins and fluoroquinolones. Ideally, Aeromonas
      should be sought in pulmonary aspirates and samples of the water where immersion
      occurred.

PMID- 30220491
TI  - [Interferon gamma release assay tests for the diagnosis of active tuberculosis].

PMID- 30220492
TI  - The long wait for lungs.

PMID- 30220493
TI  - Rapid multiplex polymerase chain reaction for detection of mcr-1 to mcr-5 genes.
AB  - A rapid (total time <2 h) and reliable multiplex polymerase chain reaction for
      screening of mcr-1 to mcr-5 genes conferring resistance to colistin has been
      developed. This technique has been tested on a collection of isolates previously
      identified as bearing mcr-1, mcr-2, and mcr-like genes and had a sensitivity and
      a specificity of 100%. Using this method, we were also able to identify a single
      isolate possessing both mcr-1 and mcr-5 genes.

PMID- 30220494
TI  - Functional Specificities of Brassinosteroid and Potential Utilization for Crop
      Improvement.
AB  - Brassinosteroid (BR) regulates many important agronomic traits and thus has great
      potential in agriculture. However, BR application is limited due to its complex
      effects on plants. The identification of specific downstream BR components and
      pathways in the crop plant rice (Oryza sativa) further demonstrates the
      feasibility of modulating BR responses to obtain desirable traits for breeding.
      Here, we review advances on how BR regulates various biological processes or
      agronomic traits such as plant architecture and grain yield in rice. We discuss
      how these functional specificities of BR can and could be utilized to enhance
      plant performance and productivity. We propose that unraveling the mechanisms
      underlying the diverse BR functions will favor BR application in molecular design
      for crop improvement.

PMID- 30220495
TI  - Sustained severe intestinal edema after nafamostat mesilate-associated
      anaphylactic reaction during hemodialysis.

PMID- 30220497
TI  - What I've learned.

PMID- 30220496
TI  - Complex humeral head fractures treated with blocked threaded wires: maintenance
      of the reduction and clinical results with two different fixation constructs.
AB  - BACKGROUND: Locking plates are the gold standard for treatment of 3-part humeral
      head fractures, although major complications range from 9% to 36%. Percutaneous
      techniques may allow vascular supply preservation, maintenance of fracture
      hematoma, scarce blood loss. Many configurations with Kirschner wires can be
      performed, generating confusion on result interpretation. We studied the
      correlation between system configuration, stability, and clinical results in
      patients with 3-part humeral head fractures treated with the same fixation system
      but with 2 different biomechanical constructs. MATERIALS AND METHODS: There were
      52 consecutive patients (19 men, 33 women; mean age, 63.1 [standard deviation,
      5.6] years; range, 48-82 years) with Hertel 7 humeral head fractures. Two
      fixation constructs composed of 3 couples (construct A) or 4 couples (construct
      B) of blocked threaded wires were used in 17 and 35 patients, respectively. At
      the final follow-up, the individual relative Constant Score (irCS) and visual
      analog scale were measured. Radiographic evaluation according to the Bahr
      criteria was performed. Statistical analysis was performed. RESULTS: The mean
      follow-up was 22 months. The mean irCS at the final follow-up was 89.7%. The mean
      irCS in patients treated with construct A and construct B was 86% and 93%,
      respectively (P = .043). One nonunion and 2 superficial infections occurred (6%).
      The postoperative reduction was excellent in 97% of patients and remained
      excellent in 89%. The mean postoperative neck shaft angle was 135.0 degrees 
      (construct A: 134.7 degrees ; construct B: 135.1 degrees ), and the final neck
      shaft angle was 132.9 degrees  (construct A: 131.3 degrees ; construct B: 133.8
      degrees ; P = .047). CONCLUSIONS: The functional and radiologic outcomes obtained
      with percutaneous fixation or locking plates are similar; however, the percentage
      of major complications after percutaneous treatment is lower. Results of
      percutaneous fixation depend on the biomechanical construct.

PMID- 30220499
TI  - Encoding of Multiple Reward-Related Computations in Transient and Sustained High
      Frequency Activity in Human OFC.
AB  - Human orbitofrontal cortex (OFC) has long been implicated in value-based decision
      making. In recent years, convergent evidence from human and model organisms has
      further elucidated its role in representing reward-related computations
      underlying decision making. However, a detailed description of these processes
      remains elusive due in part to (1) limitations in our ability to observe human
      OFC neural dynamics at the timescale of decision processes and (2) methodological
      and interspecies differences that make it challenging to connect human and animal
      findings or to resolve discrepancies when they arise. Here, we sought to address
      these challenges by conducting multi-electrode electrocorticography (ECoG)
      recordings in neurosurgical patients during economic decision making to elucidate
      the electrophysiological signature, sub-second temporal profile, and anatomical
      distribution of reward-related computations within human OFC. We found that high
      frequency activity (HFA) (70-200 Hz) reflected multiple valuation components
      grouped in two classes of valuation signals that were dissociable in temporal
      profile and information content: (1) fast, transient responses reflecting signals
      associated with choice and outcome processing, including anticipated risk and
      outcome regret, and (2) sustained responses explicitly encoding what happened in
      the immediately preceding trial. Anatomically, these responses were widely
      distributed in partially overlapping networks, including regions in the central
      OFC (Brodmann areas 11 and 13), which have been consistently implicated in reward
      processing in animal single-unit studies. Together, these results integrate
      insights drawn from human and animal studies and provide evidence for a role of
      human OFC in representing multiple reward computations.

PMID- 30220498
TI  - Replacement Bisphenols Adversely Affect Mouse Gametogenesis with Consequences for
      Subsequent Generations.
AB  - 20 years ago, accidental bisphenol A (BPA) exposure caused a sudden increase in
      chromosomally abnormal eggs from our control mice [1]. Subsequent rodent studies
      demonstrated developmental effects of exposure with repercussions on adult health
      and fertility (e.g., [2-9]; reviewed in [10-17]). Studies in monkeys, humans,
      fish, and worms suggest BPA effects extend across species (e.g., [18-30];
      reviewed in [31-33]). Widespread use has resulted in ubiquitous environmental
      contamination and human BPA exposure. Consumer concern resulted in "BPA-free"
      products produced using structurally similar bisphenols that are now detectable
      environmental and human contaminants (e.g., [34-41]). We report here studies
      initiated by meiotic changes mirroring our previous BPA experience and
      implicating exposure to BPS (a common BPA replacement) from damaged polysulfone
      cages. Like with BPA [1, 2, 5], our data show that exposure to common replacement
      bisphenols induces germline effects in both sexes that may affect multiple
      generations. These findings add to growing evidence of the biological risks posed
      by this class of chemicals. Rapid production of structural variants of BPA and
      other EDCs circumvents efforts to eliminate dangerous chemicals, exacerbates the
      regulatory burden of safety assessment, and increases environmental
      contamination. Our experience suggests that these environmental contaminants pose
      a risk not only to reproductive health but also to the integrity of the research
      environment. EDCs, like endogenous hormones, can affect diverse processes. The
      sensitivity of the germline allows us to detect effects that, although not
      immediately apparent in other systems, may induce variability that undermines
      experimental reproducibility and impedes scientific advancement.

PMID- 30220500
TI  - Suppression of Plant Immunity by Fungal Chitinase-like Effectors.
AB  - Crop diseases caused by fungi constitute one of the most important problems in
      agriculture, posing a serious threat to food security [1]. To establish
      infection, phytopathogens interfere with plant immune responses [2, 3]. However,
      strategies to promote virulence employed by fungal pathogens, especially non
      model organisms, remain elusive [4], mainly because fungi are more complex and
      difficult to study when compared to the better-characterized bacterial pathogens.
      Equally incomplete is our understanding of the birth of microbial virulence
      effectors. Here, we show that the cacao pathogen Moniliophthora perniciosa
      evolved an enzymatically inactive chitinase (MpChi) that functions as a putative
      pathogenicity factor. MpChi is among the most highly expressed fungal genes
      during the biotrophic interaction with cacao and encodes a chitinase with
      mutations that abolish its enzymatic activity. Despite the lack of chitinolytic
      activity, MpChi retains substrate binding specificity and prevents chitin
      triggered immunity by sequestering immunogenic chitin fragments. Remarkably, its
      sister species M. roreri encodes a second non-orthologous catalytically impaired
      chitinase with equivalent function. Thus, a class of conserved enzymes
      independently evolved as putative virulence factors in these fungi. In addition
      to unveiling a strategy of host immune suppression by fungal pathogens, our
      results demonstrate that the neofunctionalization of enzymes may be an
      evolutionary pathway for the rise of new virulence factors in fungi. We
      anticipate that analogous strategies are likely employed by other pathogens.

PMID- 30220501
TI  - A Single-Cell Transcriptional Atlas of the Developing Murine Cerebellum.
AB  - The cerebellum develops from a restricted number of cell types that precisely
      organize to form the circuitry that controls sensory-motor coordination and some
      higher-order cognitive processes. To acquire an enhanced understanding of the
      molecular processes that mediate cerebellar development, we performed single-cell
      RNA-sequencing of 39,245 murine cerebellar cells at twelve critical developmental
      time points. Using recognized lineage markers, we confirmed that the single-cell
      data accurately recapitulate cerebellar development. We then followed distinct
      populations from emergence through migration and differentiation, and determined
      the associated transcriptional cascades. After identifying key lineage commitment
      decisions, focused analyses uncovered waves of transcription factor expression at
      those branching points. Finally, we created Cell Seek, a flexible online
      interface that facilitates exploration of the dataset. Our study provides a
      transcriptional summarization of cerebellar development at single-cell resolution
      that will serve as a valuable resource for future investigations of cerebellar
      development, neurobiology, and disease.

PMID- 30220502
TI  - Confirmation Bias through Selective Overweighting of Choice-Consistent Evidence.
AB  - People's assessments of the state of the world often deviate systematically from
      the information available to them [1]. Such biases can originate from people's
      own decisions: committing to a categorical proposition, or a course of action,
      biases subsequent judgment and decision-making. This phenomenon, called
      confirmation bias [2], has been explained as suppression of post-decisional
      dissonance [3, 4]. Here, we provide insights into the underlying mechanism. It is
      commonly held that decisions result from the accumulation of samples of evidence
      informing about the state of the world [5-8]. We hypothesized that choices bias
      the accumulation process by selectively altering the weighting (gain) of
      subsequent evidence, akin to selective attention. We developed a novel
      psychophysical task to test this idea. Participants viewed two successive random
      dot motion stimuli and made two motion-direction judgments: a categorical
      discrimination after the first stimulus and a continuous estimation of the
      overall direction across both stimuli after the second stimulus. Participants'
      sensitivity for the second stimulus was selectively enhanced when that stimulus
      was consistent with the initial choice (compared to both, first stimuli and
      choice-inconsistent second stimuli). A model entailing choice-dependent selective
      gain modulation explained this effect better than several alternative mechanisms.
      Choice-dependent gain modulation was also established in another task entailing
      averaging of numerical values instead of motion directions. We conclude that
      intermittent choices direct selective attention during the evaluation of
      subsequent evidence, possibly due to decision-related feedback in the brain [9].
      Our results point to a recurrent interplay between decision-making and selective
      attention.

PMID- 30220503
TI  - Stepwise cis-Regulatory Changes in ZCN8 Contribute to Maize Flowering-Time
      Adaptation.
AB  - Maize (Zea mays ssp. mays) was domesticated in southwestern Mexico ~9,000 years
      ago from its wild ancestor, teosinte (Zea mays ssp. parviglumis) [1]. From its
      center of origin, maize experienced a rapid range expansion and spread over 90
      degrees  of latitude in the Americas [2-4], which required a novel flowering-time
      adaptation. ZEA CENTRORADIALIS 8 (ZCN8) is the maize florigen gene and has a
      central role in mediating flowering [5, 6]. Here, we show that ZCN8 underlies a
      major quantitative trait locus (QTL) (qDTA8) for flowering time that was
      consistently detected in multiple maize-teosinte experimental populations.
      Through association analysis in a large diverse panel of maize inbred lines, we
      identified a SNP (SNP-1245) in the ZCN8 promoter that showed the strongest
      association with flowering time. SNP-1245 co-segregated with qDTA8 in maize
      teosinte mapping populations. We demonstrate that SNP-1245 is associated with
      differential binding by the flowering activator ZmMADS1. SNP-1245 was a target of
      selection during early domestication, which drove the pre-existing early
      flowering allele to near fixation in maize. Interestingly, we detected an
      independent association block upstream of SNP-1245, wherein the early flowering
      allele that most likely originated from Zea mays ssp. mexicana introgressed into
      the early flowering haplotype of SNP-1245 and contributed to maize adaptation to
      northern high latitudes. Our study demonstrates how independent cis-regulatory
      variants at a gene can be selected at different evolutionary times for local
      adaptation, highlighting how complex cis-regulatory control mechanisms evolve.
      Finally, we propose a polygenic map for the pre-Columbian spread of maize
      throughout the Americas.

PMID- 30220505
TI  - Effect of loading frequency on cyclic fatigue lifetime of a standard-diameter
      implant with an internal abutment connection.
AB  - OBJECTIVE: To investigate the effect of loading frequency on the fatigue lifetime
      of one standard-diameter titanium dental implant system. METHODS: Thirty-six
      titanium dental implant specimens (Bone Level RC, Straumann) were assembled
      following manufacturer's instructions and torqued into cylindrical holder blocks
      following the apparatus specified by the ISO 14801 test standard. Stainless steel
      loading hemispheres were bonded on the abutments with a moment arm of 11mm. The
      holder blocks had layers of differing stiffness to simulate human jaw bone.
      Constant-stress fatigue lifetime testing was conducted at two frequencies (2Hz
      and 15Hz) with a stress ratio of 0.1 until fracture in deionized water at 37
      degrees C on servo-hydraulic load frames (MTS). The fractured specimens were
      retrieved and examined using fractographic technique to determine the failure
      mode. The lifetime data were fit to a general log-linear regression model.
      RESULTS: The coefficient for the load amplitude term of the regression model
      indicated that increasing load amplitude had a statistically significant negative
      effect on the fatigue lifetime. The coefficients for the cyclic frequency term
      and the load-frequency interaction term were not significantly different from
      zero, which indicated that increasing loading frequency did not have an influence
      on the number of cycles to failure. Fractographic analysis showed that all
      specimens exhibited an identical combined fracture of abutment and abutment screw
      adjacent to the bone level. SIGNIFICANCE: Higher loading frequency at least up to
      15Hz may be used for future studies of some implant systems to improve the
      efficiency of fatigue testing.

PMID- 30220504
TI  - Insights into the Evolution of Multicellularity from the Sea Lettuce Genome.
AB  - We report here the 98.5 Mbp haploid genome (12,924 protein coding genes) of Ulva
      mutabilis, a ubiquitous and iconic representative of the Ulvophyceae or green
      seaweeds. Ulva's rapid and abundant growth makes it a key contributor to coastal
      biogeochemical cycles; its role in marine sulfur cycles is particularly important
      because it produces high levels of dimethylsulfoniopropionate (DMSP), the main
      precursor of volatile dimethyl sulfide (DMS). Rapid growth makes Ulva attractive
      biomass feedstock but also increasingly a driver of nuisance "green tides."
      Ulvophytes are key to understanding the evolution of multicellularity in the
      green lineage, and Ulva morphogenesis is dependent on bacterial signals, making
      it an important species with which to study cross-kingdom communication. Our
      sequenced genome informs these aspects of ulvophyte cell biology, physiology, and
      ecology. Gene family expansions associated with multicellularity are distinct
      from those of freshwater algae. Candidate genes, including some that arose
      following horizontal gene transfer from chromalveolates, are present for the
      transport and metabolism of DMSP. The Ulva genome offers, therefore, new
      opportunities to understand coastal and marine ecosystems and the fundamental
      evolution of the green lineage.

PMID- 30220506
TI  - Biofilm formation on restorative materials and resin composite cements.
AB  - OBJECTIVES: Monolithic zirconia, polymer-infiltrated ceramic and acrylate polymer
      cemented with resin composite cement have recently been identified as prosthetic
      treatment options for zirconia implants. The aim of the present study is to
      determine in vitro, to what extent bacteria adhere to these materials. METHODS:
      Disks made of zirconia (Vita YZ [YZ]), polymer-infiltrated ceramic (Vita Enamic
      [VE]), acrylate polymer (Vita CAD-Temp [CT]), self-adhesive cement (RelyX Unicem
      2 Automix [RUN]) and of two different adhesive cements (RelyX Ulimate [RUL] and
      Vita Adiva F-Cem [VAF]) were produced. The biofilm formation of three bacterial
      species (Streptococcus sanguinis, Fusobacterium nucleatum, Porphyromonas
      gingivalis) on each material was assessed over 72h using a flow chamber system.
      The biofilms were quantified by crystal violet staining (optical density 595nm)
      and visualized using SEM. The inorganic composition of the different materials
      was analyzed and the wettability of the specimens was measured. RESULTS: For the
      restorative materials lowest biofilm formation was found on CT: OD 0.5+/-0.1,
      followed by VE: OD 0.8+/-0.1 and YZ: OD 1.4+/-0.3. The biofilm formation on resin
      composite cements was significantly lower on VAF: OD 0.6+/-0.1 than for RUL: OD
      0.9+/-0.1 and RUN: OD 1.0+/-0.1. A high wettability of the specimens with
      saliva/serum mixture tended to result in a higher biofilm formation. Correlations
      were obtained between the organic/inorganic composition of the materials and the
      polar/dispersive part of the surface free energy. SIGNIFICANCE: Three-species
      biofilm formation on restorative and cement materials strongly relies on the
      materials composition. If the restorative material CT and cement VAF also prevent
      excessive biofilm formation in a clinical situation should be further
      investigated.

PMID- 30220507
TI  - Multifaceted roles of environmental factors toward dental implant performance:
      Observations from clinical retrievals and in vitro testing.
AB  - OBJECTIVE: Oral bacteria and periodontal pathogen have been predominantly linked
      with early- and late- stage failures of titanium (Ti) dental implants (DI)
      respectively. This study is based on the hypothesis that bacterial colonization
      can damage the surface oxide (TiO2) layer. Early-failed DI were compared with DI
      post-in vitro immersion in early colonizing oral bacteria; late failed DI were
      weighed against DI immersed in late colonizing anaerobic pathogens. METHODS:
      Retrieval analysis: Seven early- stage failed implants with five of them
      connected to healing abutments (HAs), and ten late- stage failed retrievals were
      subjected to surface analysis. Bacteria immersion test: Three dental implants
      each were immersed in polycultures containing (i) early colonizers (Streptococcus
      mutans, S. salivarius, S. sanguinis) (ii) late colonizers (Porphyromonas
      gingivalis, Aggregatibacter actinomycetemcomitans). The implants were immersed
      for 30 days to simulate the healing period and bacterial biofilm adhesion.
      Optical microscope, x-ray photoelectron spectroscopy (XPS), and electrochemical
      test were performed to analyze the surface- morphology, chemistry, and potential
      respectively. RESULTS: Early colonizers inflicted surface morphological damage
      (discoloration and pitting). Even though, XPS detected thinner oxide layer in 2/3
      early retrievals, XPS and electrochemical tests illustrated that the TiO2 layer
      was intact in HAs, and in DI post- immersion. Late colonizers also caused similar
      morphological damage (discoloration and pitting), while mechanical wear was
      evident with scratches, cracks, and mechanical fracture observed in late-stage
      retrievals. XPS indicated thinner oxide layer in late-stage retrievals (3/4), and
      in DI post-immersion in late colonizers. This was reflected in electrochemical
      test results post-immersion but not in the late-stage retrievals, which suggested
      an intact surface with corrosion resistance. SIGNIFICANCE: This study concluded
      that bacteria could negatively affect implant surface with late colonizers
      demonstrating more pronounced damage on the surface morphology and chemistry.

PMID- 30220508
TI  - Effect of aging and testing method on bond strength of CAD/CAM fiber-reinforced
      composite to dentin.
AB  - OBJECTIVES: To evaluate and compare the outcomes of shear (S) and microtensile
      (MUT) bond strength tests of CAD/CAM fiber-reinforced composite (FRC) to dentin.
      Aging with either fatigue or thermocycling were conducted for comparison with
      baseline microtensile group. METHODS: CAD/CAM FRC (Trinia, Bicon LLC, Boston,
      USA) blocks were milled to 3-mm diameter cylinders for shear and to blocks
      (5*5*5mm) for MUT. Sixty extracted human molars were flattened to obtain dentin
      surfaces and randomly divided in four groups (n=15): (1) SC: samples tested in
      shear 24h after bonding; (2) MUTC: samples tested in MUT 24h after bonding); (3)
      MUTF: samples submitted to mechanical fatigue prior to MUT test, and; (4) MUTT:
      thermocycling prior to MUT test. Bonding system was applied onto the FRC material
      (Cera-Resin Bond, CRB, Shofu Dental, Kyoto, Japan). A conventional three-step
      adhesive system (All-bond 3, Bisco, Schaumburg, USA) was use with a self-cure
      resin cement (C&B resin cement, Bisco, Schaumburg, USA). Bond strength tests were
      conducted at 0.75mm/min and data analyzed using Weibull distribution (p<0.05).
      RESULTS: Weibull contour plots showed a significantly lower characteristic
      strength (eta) and Weibull modulus (m) for SC (eta=6.9MPa and m=1.4) compared to
      MUTC (eta=20.9MPa and m=4.5). Fatigued and thermocycled MUT groups presented
      significantly reduced characteristic strength (eta=3.1MPa and eta=4.1MPa,
      respectively) compared to MUTC. Weibull modulus was significantly reduced only
      for SC and MUTF groups compared MUTC. Failure predominantly occurred at the
      cement/FRC interface. SIGNIFICANCE: FRC bonded to dentin samples presented lower
      Weibull modulus and characteristic bond strength when immediately tested in shear
      compared to microtensile. Aging through thermocycling or mechanical fatigue
      significantly reduced the characteristic strength in microtensile testing, with
      the majority of failures emerging between restoration material and cement
      interface.

PMID- 30220509
TI  - Distinct Laminar Processing of Local and Global Context in Primate Primary Visual
      Cortex.
AB  - Visual perception is affected by spatial context. In visual cortex, neuronal
      responses to stimuli inside the receptive field (RF) are suppressed by stimuli in
      the RF surround. To understand the circuits and cortical layers processing
      spatial context, we simultaneously recorded across all layers of macaque primary
      visual cortex while presenting stimuli at increasing distances from the recorded
      cells' RF. We find that near versus far-surround stimuli activate distinct
      layers, thus revealing unique laminar contributions to the processing of local
      and global spatial context. Stimuli in the near-surround evoke the earliest
      subthreshold responses in superficial and upper-deep layers, and earliest
      suppression of spiking responses in superficial layers. Conversely, far-surround
      stimuli evoke the earliest subthreshold responses in feedback-recipient layer 1
      and lower-deep layers, and earliest suppression of spiking responses almost
      simultaneously in all layers, except 4C, where suppression emerges last. Our
      results suggest distinct circuits for local and global signal integration.

PMID- 30220510
TI  - Sequential Nonlinear Filtering of Local Motion Cues by Global Motion Circuits.
AB  - Many animals guide their movements using optic flow, the displacement of
      stationary objects across the retina caused by self-motion. How do animals
      selectively synthesize a global motion pattern from its local motion components?
      To what extent does this feature selectivity rely on circuit mechanisms versus
      dendritic processing? Here we used in vivo calcium imaging to identify pre- and
      postsynaptic mechanisms for processing local motion signals in global motion
      detection circuits in Drosophila. Lobula plate tangential cells (LPTCs) detect
      global motion by pooling input from local motion detectors, T4/T5 neurons. We
      show that T4/T5 neurons suppress responses to adjacent local motion signals
      whereas LPTC dendrites selectively amplify spatiotemporal sequences of local
      motion signals consistent with preferred global patterns. We propose that
      sequential nonlinear suppression and amplification operations allow optic flow
      circuitry to simultaneously prevent saturating responses to local signals while
      creating selectivity for global motion patterns critical to behavior.

PMID- 30220511
TI  - Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating
      Astrocyte-Mediated Neuroinflammation.
AB  - Astrocyte dysfunction and inflammation are associated with the pathogenesis of
      major depressive disorder (MDD). However, the mechanisms underlying these effects
      remain largely unknown. Here, we found that multiple endocrine neoplasia type 1
      (Men1; protein: menin) expression is attenuated in the brain of mice exposed to
      CUMS (chronic unpredictable mild stress) or lipopolysaccharide. Astrocyte
      specific reduction of Men1 (GcKO) led to depressive-like behaviors in mice. We
      observed enhanced NF-kappaB activation and IL-1beta production with menin
      deficiency in astrocytes, where depressive-like behaviors in GcKO mice were
      restored by NF-kappaB inhibitor or IL-1beta receptor antagonist. Importantly, we
      identified a SNP, rs375804228, in human MEN1, where G503D substitution is
      associated with a higher risk of MDD onset. G503D substitution abolished menin
      p65 interactions, thereby enhancing NF-kappaB activation and IL-1beta production.
      Our results reveal a distinct astroglial role for menin in regulating
      neuroinflammation in depression, indicating that menin may be an attractive
      therapeutic target in MDD.

PMID- 30220512
TI  - Gap Junctions Contribute to Differential Light Adaptation across Direction
      Selective Retinal Ganglion Cells.
AB  - Direction-selective ganglion cells (DSGCs) deliver signals from the retina to
      multiple brain areas to indicate the presence and direction of motion. Delivering
      reliable signals in response to motion is critical across light levels. Here we
      determine how populations of DSGCs adapt to changes in light level, from
      moonlight to daylight. Using large-scale measurements of neural activity, we
      demonstrate that the population of DSGCs switches encoding strategies across
      light levels. Specifically, the direction tuning of superior (upward)-preferring
      ON-OFF DSGCs becomes broader at low light levels, whereas other DSGCs exhibit
      stable tuning. Using a conditional knockout of gap junctions, we show that this
      differential adaptation among superior-preferring ON-OFF DSGCs is caused by
      connexin36-mediated electrical coupling and differences in effective GABAergic
      inhibition. Furthermore, this adaptation strategy is beneficial for balancing
      motion detection and direction estimation at the lower signal-to-noise ratio
      encountered at night. These results provide insights into how light adaptation
      impacts motion encoding in the retina.

PMID- 30220513
TI  - Why are stimulant medication prescriptions rising globally?

PMID- 30220515
TI  - Service user reviewers: extending peer review in The Lancet Psychiatry.

PMID- 30220514
TI  - Trends in attention-deficit hyperactivity disorder medication use: a
      retrospective observational study using population-based databases.
AB  - BACKGROUND: The use of medications to treat attention deficit hyperactivity
      disorder (ADHD) has increased, but the prevalence of ADHD medication use across
      different world regions is not known. Our objective was to determine regional and
      national prevalences of ADHD medication use in children and adults, with a
      specific focus on time trends in ADHD medication prevalence. METHODS: We did a
      retrospective, observational study using population-based databases from 13
      countries and one Special Administrative Region (SAR): four in Asia and
      Australia, two in North America, five in northern Europe, and three in western
      Europe. We used a common protocol approach to define study populations and
      parameters similarly across countries and the SAR. Study populations consisted of
      all individuals aged 3 years or older between Jan 1, 2001, and Dec 31, 2015
      (dependent on data availability). We estimated annual prevalence of ADHD
      medication use with 95% CI during the study period, by country and region and
      stratified by age and sex. We reported annual absolute and relative percentage
      changes to describe time trends. FINDINGS: 154.5 million individuals were
      included in the study. ADHD medication use prevalence in 2010 (in children aged 3
      18 years) varied between 0.27% and 6.69% in the countries and SAR assessed (0.95%
      in Asia and Australia, 4.48% in North America, 1.95% in northern Europe, and
      0.70% in western Europe). The prevalence of ADHD medication use among children
      increased over time in all countries and regions, and the absolute increase per
      year ranged from 0.02% to 0.26%. Among adults aged 19 years or older, the
      prevalence of any ADHD medication use in 2010 varied between 0.003% and 1.48%
      (0.05% in Asia and Australia, 1.42% in North America, 0.47% in northern Europe,
      and 0.03% in western Europe). The absolute increase in ADHD medication use
      prevalence per year ranged from 0.0006% to 0.12%. Methylphenidate was the most
      commonly used ADHD medication in most countries. INTERPRETATION: Using a common
      protocol and data from 13 countries and one SAR, these results show increases
      over time but large variations in ADHD medication use in multiple regions. The
      recommendations of evidence-based guidelines need to be followed consistently in
      clinical practice. Further research is warranted to describe the safety and
      effectiveness of ADHD medication in the short and long term, and to inform
      evidence-based guidelines, particularly in adults. FUNDING: None.

PMID- 30220516
TI  - (Membrane) Protein Production in Context.
AB  - Great progress has been made in elucidating the structural and mechanistic basis
      of (membrane) protein production. Here, we attempt to look ahead and indicate
      four directions in which our understanding of the protein production process can
      grow: (i) determine how the molecular mechanisms influence higher-level
      processes, such as the distribution of protein copy number over a population of
      cells or the cell growth rate; (ii) explore the functional landscape that the
      molecular mechanisms of protein production exist in, for instance by comparing
      membrane protein insertion mechanisms; (iii) uncover the life history of proteins
      - that is, what happens to them between their synthesis and degradation; and (iv)
      determine, and connect by calculation, the numbers that are associated with
      (membrane) protein production.

PMID- 30220517
TI  - Pneumococcal disease and conjugate vaccines.

PMID- 30220519
TI  - Evaluation of Obstetrics & Gynecology Ultrasound Curriculum and Self-Reported
      Competency of Final-Year Canadian Residents.
AB  - OBJECTIVE: Ultrasonography in obstetrics and gynaecology (OB/GYN) is a vital
      component of patient assessment, diagnosis, and management. Standards for
      Canadian obstetrician-gynecologists' ultrasound skills are limited and vague. The
      primary objective was to audit the current curriculum administered to Canadian
      OB/GYN residents. The secondary objective was to understand self-perceived
      competency of final-year residents in performing OB/GYN ultrasound. We also
      sought to identify perceived barriers to incorporation of ultrasound into
      practice. METHODS: A cross-sectional questionnaire, distributed to two cohorts of
      final-year Canadian OB/GYN residents, asked about ultrasound training they
      received and their perceived competency with respect to specific ultrasound
      skills. Respondents also answered questions on possible perceived obstacles to
      independently using ultrasound after graduation. RESULTS: All Canadian residency
      programs were represented among the 81 respondents out of the possible 167
      participants (49%). Ultrasound training varied in its delivery and quantity. The
      majority of training time was dedicated to obstetrics, with minimal focus on
      gynaecology. Self-reported competency for obstetric ultrasound was high, whereas
      that for gynaecologic ultrasound was variable. The main barrier to incorporating
      ultrasound into future practice was lack of adequate training. CONCLUSIONS:
      Canadian OB/GYN programs lack standardisation of ultrasound training. The
      imbalance in training between OB/GYN ultrasound may influence the low levels of
      self-reported competency in gynaecologic skills in residents. Standardization of
      ultrasound education and increasing gynaecologic ultrasound training in residency
      are the necessary first steps in preparing OB/GYN graduates to use ultrasound.

PMID- 30220518
TI  - Microbiological diagnosis of catheter-related infections.
AB  - This revision describes in detail the different diagnostic techniques of catheter
      related infection, both in terms of catheter removal and preservation. Culture
      techniques based on catheter withdrawal are classified depending on the detection
      of extraluminal and/or intraluminal colonization, and new methodologies are
      described. In general, the most important recommendations are: (a) do not send
      for culture catheter tips without suspicion of infection, (b) Maki's technique is
      the standard for detecting extraluminal colonization, (c) take 2 pairs of
      peripheral blood cultures before starting antibiotic treatment, (d) use skin and
      connections/connectors cultures for the conservative diagnosis due to their high
      negative predictive value (Gram and culture), and (e) take differential
      quantitative blood cultures though all catheter lumens and through a peripheral
      vein.

PMID- 30220520
TI  - An Interleukin-1 beta (IL1B) haplotype linked with psychosis transition is
      associated with IL1B gene expression and brain structure.
AB  - We investigated IL1B genetic variation previously associated with risk for
      transition to psychosis for its association with gene expression in human post
      mortem dorsolateral prefrontal cortex (DLPFC) from 74 (37 schizophrenia, 37
      control) individuals and brain structure in 92 (44 schizophrenia, 48 control)
      living individuals. The IL1B A-G-T 'risk for psychosis transition' haplotype
      (rs16944|rs4848306|rs12621220) was associated with upregulation of IL1B mRNA
      expression in the DLPFC as well as reduced total grey matter and left middle
      frontal volumes and enlarged left lateral ventricular volume. Our results suggest
      IL1B genetic variation may confer psychosis risk via elevated mRNA expression
      and/or brain structure abnormalities.

PMID- 30220521
TI  - Transcription Factors Drive Tet2-Mediated Enhancer Demethylation to Reprogram
      Cell Fate.
AB  - Here, we report DNA methylation and hydroxymethylation dynamics at nucleotide
      resolution using C/EBPalpha-enhanced reprogramming of B cells into induced
      pluripotent cells (iPSCs). We observed successive waves of hydroxymethylation at
      enhancers, concomitant with a decrease in DNA methylation, suggesting active
      demethylation. Consistent with this finding, ablation of the DNA demethylase Tet2
      almost completely abolishes reprogramming. C/EBPalpha, Klf4, and Tfcp2l1 each
      interact with Tet2 and recruit the enzyme to specific DNA sites. During
      reprogramming, some of these sites maintain high levels of 5hmC, and enhancers
      and promoters of key pluripotency factors become demethylated as early as 1 day
      after Yamanaka factor induction. Surprisingly, methylation changes precede
      chromatin opening in distinct chromatin regions, including Klf4 bound sites,
      revealing a pioneer factor activity associated with alternation in DNA
      methylation. Rapid changes in hydroxymethylation similar to those in B cells were
      also observed during compound-accelerated reprogramming of fibroblasts into
      iPSCs, highlighting the generality of our observations.

PMID- 30220522
TI  - Prediction of rat liver transplantation outcomes using energy metabolites
      measured by microdialysis.
AB  - BACKGROUND: Warm ischemia jeopardizes graft quality and recipient survival in
      donation after cardiac death (DCD) transplantation. Currently, there is no system
      to objectively evaluate the liver quality from DCD. The present study tried to
      use energy metabolites to evaluate the donor liver quality. METHODS: We divided
      195 Sprague-Dawley rats into five groups: the control (n = 39), warm ischemic
      time (WIT) 15 min (n = 39), WIT 30 min (n = 39), WIT 45 min (n = 39), and WIT 60
      min (n = 39) groups. Three rats from each group were randomly selected for
      pretransplant histologic evaluation of warm ischemia-related damage. The
      remaining 36 rats were randomly divided into donors and recipients of 18 liver
      transplantations, and were subjected to postoperative liver function and survival
      analyses. Between cardiac arrest and cold storage, liver energy metabolites
      including glucose, lactate, pyruvate, and glycerol were measured by
      microdialysis. The lactate to pyruvate ratio (LPR) was calculated. RESULTS: The
      changes in preoperative pathology with warm ischemia were inconspicuous, but the
      trends in postoperative pathology and aminotransferase levels were consistent
      with preoperative energy metabolite measurements. The 30-day survival rates of
      the control and WIT 15, 30, 45, and 60 min groups were 100%, 81.82%, 76.92%,
      58.33%, and 25.00%, respectively. The areas under the receiver operating
      characteristic curves of glucose, lactate, glycerol, and LPR were 0.87, 0.88,
      0.88, and 0.92, respectively. CONCLUSION: Glucose, lactate, glycerol, and LPR are
      predictors of graft quality and survival outcomes in DCD transplantation.

PMID- 30220524
TI  - More than just teddy bears: Unconventional transmission agents in the operating
      room.
AB  - INTRODUCTION: Surgical site infection (SSI) following orthopedic surgery can have
      a substantial impact on patients and families. The rate remains high, ranging
      from 0.5% to 8.5% in pediatric spine surgery. It is common to allow children to
      bring a teddy bear (or similar toy) to the surgical ward to help reduce the
      stress of surgery. We hypothesize that despite their known benefits for children,
      teddies would increase the bacterial load in the surgical room. METHODS: A
      blinded descriptive study was conducted from June 2015 to September 2016. The
      study included children entering the hospital through the emergency ward for a
      traumatic cause requiring surgery. Patients admitted for infectious problems and
      those who had been hospitalized less than 6 months before the inclusion date were
      excluded. A picture of the teddy was taken and stored in a blind fashion. The
      AFNOR (Association francaise de normalisation) standardized rules for
      bacteriological surface control and the ISO/DIS 14698 protocol were strictly
      followed. Two independent observers performed blind bacteriologic analyses of the
      teddy bears with bacteria identification and colony counts. Photos of the teddy
      bears were then analyzed by two blinded, independent observers: one doctor and
      one parent from outside the hospital. Cleanliness and fluffiness of the toy was
      evaluated using a numeric scale. RESULTS: Bacteria were identified on 100% of the
      53 teddies included. The mean number of bacteria was 182.5+/-49.8 CFU/25 cm2.
      Eight teddies (15.1%) tested positive for potential pathogenic bacteria (two
      staphylococcus aureus, one acinetobacter ursingii, four acinetobacter baumannii,
      one pseudomonas stutzeri). Three teddies (5.7%) tested positive for fungi. The
      median cleanliness score was 2 (interquartile range (IQR)=1) if rated by the
      doctor and 2 (IQR=1) if rated by the parent. No statistical difference was found
      between these two values in the global teddy bear population. We found no any
      statistical link between the number of CFUs and the cleanliness scores given by
      the doctor. The median fluffiness score given by the parent was 2 (IQR=1).
      Looking at the correlative CFUs, we found a statistically significant difference
      between each stage of fluffiness with a higher stage showing higher CFU
      (P<0.0001). CONCLUSION: Despite their documented benefits for the child, teddy
      bears are not appropriate in the surgical room.

PMID- 30220523
TI  - Potentially preventable tuberculosis cases in children exposed to a contaminant
      case.
AB  - Early screening is recommended in children exposed to a contagious case of
      tuberculosis (TB), to prevent rapid progression to active TB. The aim of this
      study was to evaluate the percentage of potentially preventable cases of
      pediatric TB stemming from inadequate screening. The data gathered on children
      aged 0 to 10 years, who were evaluated by the Paris Center for TB Control
      (CLAT75) between January 2009 and December 2013, were extracted and
      retrospectively analyzed. French National Guidelines for screening were used as
      reference. During the study period, 1232 children 0-10 years were screened,
      because of a known exposure to an index case, including 124 (10%) with criteria
      for latent tuberculosis infection (LTBI) and 26 (2%) with active TB. Twelve
      additional cases of TB were reported, diagnosed based on symptoms or systematic
      exams. As a whole, 68% of pediatric TB cases were diagnosed at screening around
      an adult index case, highlighting the quality of the screening network. Among the
      38 TB cases, 19 (50%) had a missed opportunity for potential prevention, due to
      the absence of screening despite a known contaminant (n=2) or to screening not in
      compliance with current recommendations (n=17). Delayed first evaluation was the
      most frequent error of the screening procedures. In conclusion, despite the
      quality of the screening network set up in Paris, half of the pediatric TB cases
      in this study did not undergo the recommended screening procedures. A significant
      reduction in the number of pediatric TB cases can be expected through the
      optimization of screening networks.

PMID- 30220525
TI  - Using a Large Bore Sheath to Untwist Tortuous Iliac Arteries at EVAR: A Simple
      and Effective Technique.

PMID- 30220526
TI  - Use of a Temporary Vascular Shunt Across the Knee Joint for Proximal Arterial
      Injury of the Extremity.

PMID- 30220527
TI  - Increasing Incidence of Thoracic Aortic Aneurysm Repair in Germany in the
      Endovascular Era: Secondary Data Analysis of the Nationwide German DRG Microdata.
AB  - OBJECTIVES: Nationwide population based data on epidemiology and surgical
      treatment of descending thoracic aortic aneurysms (dTAAs) are not available for
      Germany. The aim was to assess the in hospital incidence, and to report outcomes
      of patients who received surgical treatment. METHODS: Data were acquired by
      analysing the diagnosis related group (DRG) statistics of the German Federal
      Statistical Office. All inpatient cases of ruptured (rTAA, ICD Code I71.1) or non
      ruptured dTAA (nrTAA; I71.2) who received thoracic endovascular (TEVAR; OPS
      procedure code 5-38a.7/70/8/80) or open aortic repair (OAR; OPS 5-384.3) between
      2005 and 2014 were included. To adjust for sex, age, medical risk (Elixhauser
      comorbidity score), type of procedure, and type of admission, a multilevel
      multivariable regression model with robust error variance was applied. The
      primary outcome was in hospital mortality; secondary outcomes were organ
      complications. A volume outcome analysis was performed. RESULTS: A total of
      48,098 cases of TAA (5,848, 12.2% rTAA) were identified. The average age was 69
      +/- 12 years. 65.2% were male. Frequent comorbidities were hypertension (74.9%),
      peripheral artery disease (including abdominal aortic aneurysm, 42.6%), other
      heart diseases (41.6%), coronary heart disease (26.2%), and renal failure
      (22.5%). Surgical treatment was received by 4969 patients (10.3%): 4057 TEVAR
      (81.6%) and 912 OAR (18.4%) procedures. Mortality for rTAA was 42.9% (OAR) and
      22.3% (TEVAR). It was 10.5% and 3.7% for nrTAA, respectively. Rupture, increasing
      age, and higher comorbidity score were significantly associated with higher
      mortality (RR 6.66, 5.33-8.25; 1.28, 1.17-1.40; and 1.06, 1.05-1.08,
      respectively). Endovascular treatment was associated with lower mortality (RR
      0.31, 0.23-0.41). Hospital volume was not significantly associated with in
      hospital mortality. CONCLUSIONS: Eighty per cent of patients treated surgically
      for a dTAA receive endovascular therapy, with low peri-operative mortality in non
      ruptured cases. Elective endovascular repair should be considered for individuals
      at a high risk of rupture who are fit for surgery. Open repair, increased age,
      and a high comorbidity score are associated with higher mortality.

PMID- 30220529
TI  - Voice Disorder and Burnout Syndrome in Teachers.
AB  - OBJECTIVE: The objective of this study was to assess the association between
      burnout syndrome and the likely presence of voice disorders among teachers from a
      public elementary school in the country town of Sergipe. METHODS: This is a cross
      sectional study in which 208 teachers completed the following questionnaires: the
      Condition of Vocal Production-Teacher (CPV-P), the Screening Index for Voice
      Disorder (SIVD), and the Burnout Syndrome Evaluation Questionnaire (CESQT).
      RESULTS: Of the 208 teachers, 76.9% were women, 77.9% came from rural areas, and
      64.4% were likely to have a voice disorder. Teachers with a career length of over
      15 years were almost twice as likely to have a voice disorder. Of the symptoms
      listed in the SIVD, the following were most prevalent: dry throat (88.1%),
      hoarseness (84.4%), and fatigue when speaking (82.1%). Among the burnout
      subscales, psychic exhaustion was the most common (30.3%). Analyses revealed that
      probable voice disorder was associated with psychic exhaustion with an odds ratio
      of 1.78 (P <0.001, chi2 = 84.1%). Teachers with positive scores on two to four
      burnout subscales had an odds ratio of 4.01 (P = 0.013, chi2 = 86.2%) for a
      probable voice disorder compared with those with positive scores on zero to one
      subscale. CONCLUSIONS: The present results confirmed that burnout syndrome was
      associated with the presence of a probable voice disorder.

PMID- 30220528
TI  - Voice Quality as Therapeutic Outcome in Laryngopharyngeal Reflux Disease: A
      Prospective Cohort Study.
AB  - PURPOSE: To study the usefulness of voice quality as therapeutic outcome in
      laryngopharyngeal reflux disease. MATERIAL AND METHODS: A total of 80 patients
      with reflux finding score (RFS) > 7 and reflux symptom index (RSI) > 13 were
      treated with pantoprazole, diet, and lifestyle recommendations for 3 months. The
      therapeutic effectiveness was assessed with RSI; RFS; Voice Handicap Index;
      blinded Grade, Roughness, Breathiness, Asthenia, Strain, and Instability
      (GRBASI); aerodynamic and a panel of acoustic measurements before and after
      treatment. A correlation analysis between symptoms, videolaryngostroboscopic
      signs, and acoustic measurements was conducted. RESULTS: Compared to baseline,
      means of RSI, RFS, Voice Handicap Index, perceptual dysphonia, and roughness
      significantly decreased. Significant improvements of phonatory quotient, percent
      jitter, percent shimmer, Relative Average Perturbation, Pitch Perturbation
      Quotient, Phonatory F0 Range, Amplitude Perturbation Quotient, smooth Amplitude
      Perturbation Quotient, and Peak-to-Peak Amplitude Variation were found at the end
      of treatment. Studies of correlation did not identify relevant correlation
      between videolaryngostroboscopic signs, especially vocal folds edema, and
      objective voice quality evaluations. CONCLUSION: Voice quality assessments can
      help to better understand voice disorders and can be used as indicators of the
      treatment effectiveness in patients with laryngopharyngeal reflux-related
      symptoms.

PMID- 30220530
TI  - The mTOR-inhibitor Sirolimus decreases the cyclosporine-induced expression of the
      oncogene ATF3 in human keratinocytes.
AB  - BACKGROUND: Due to their immunosuppressive therapy, organtransplant recipients
      (OTRs) exhibit a high incidence for the development of cutaneous squamous cell
      carcinoma (cSCC). Randomized studies of kidney-transplanted patients indicate a
      significant lower susceptibility for cSCC among patients receiving the mTOR
      inhibitor Sirolimus, compared to patients without mTOR-regimen. The exact
      mechanism, how mTOR inhibition affects keratinocyte carcinogenesis remains
      unclear. OBJECTIVE: Our aim was to investigate the impact of Sirolimus on the
      expression level of the oncogene ATF3, which is involved in the development and
      progression of cSCC. METHODS: We incubated human keratinocytes, cSSC cell lines
      and 3D skin equivalents with Sirolimus, exposed the cells to calcineurin
      inhibitors (CNI) and UVA-radiation and measured the expression level of ATF3 by
      real-time PCR and western blot. RESULTS: We show that Sirolimus downregulates the
      expression of ATF3 induced by cyclosporine or cyclosporine plus UV-radiation in
      keratinocytes. In line with this we demonstrate a decrease in ATF3 expression, by
      incubating 3D skin equivalents with Sirolimus prior to cyclosporine and UV-light.
      However, Sirolimus has no significant impact on the ATF3 expression levels of
      cyclosporine stimulated cSCC cell lines. CONCLUSION: Taken together, our study
      demonstrates that Sirolimus downregulates the CNI or UV-induced ATF3 expression
      in human keratinocytes, which could be a potential molecular mechanism how
      Sirolimus reduces cSCC in OTRs. The lack of ATF3 suppression by Sirolimus in cSCC
      cell lines fits to observations from clinical studies which demonstrated a
      clinical benefit from the switch to a mTOR-regimen in patients with low tumor
      burden in early stage of disease.

PMID- 30220531
TI  - Dynamics of the HIV outbreak and response in Scott County, IN, USA, 2011-15: a
      modelling study.
AB  - BACKGROUND: In November, 2014, a cluster of HIV infections was detected among
      people who inject drugs in Scott County, IN, USA, with 215 HIV infections
      eventually attributed to the outbreak. This study examines whether earlier
      implementation of a public health response could have reduced the scale of the
      outbreak. METHODS: In this modelling study, we derived weekly case data from the
      HIV outbreak in Scott County, IN, and on the uptake of HIV testing, treatment,
      and prevention services from publicly available reports from the US Centers for
      Disease Control and Prevention (CDC) and researchers from Indiana. Our primary
      objective was to determine if an earlier response to the outbreak could have had
      an effect on the number of people infected. We computed upper and lower bounds
      for cumulative HIV incidence by digitally extracting data from published images
      from a CDC study using Bio-Rad avidity incidence testing to estimate the recency
      of each transmission event. We constructed a generalisation of the susceptible
      infectious-removed model to capture the transmission dynamics of the HIV
      outbreak. We computed non-parametric interval estimates of the number of
      individuals with an undiagnosed HIV infection, the case-finding rate per
      undiagnosed HIV infection, and model-based bounds for the HIV transmission rate
      throughout the epidemic. We used these models to assess the potential effect if
      the same intervention had begun at two key timepoints earlier than the actual
      date of the initiation of efforts to control the outbreak. FINDINGS: The upper
      bound for undiagnosed HIV infections in Scott County peaked at 126 around Jan 10,
      2015, over 2 months before the Governor of Indiana declared a public health
      emergency on March 26, 2015. Applying the observed case-finding rate scale-up to
      earlier intervention times suggests that an earlier public health response could
      have substantially reduced the total number of HIV infections (estimated to have
      been 183-184 infections by Aug 11, 2015). Initiation of a response on Jan 1,
      2013, could have suppressed the number of infections to 56 or fewer, averting at
      least 127 infections; whereas an intervention on April 1, 2011, could have
      reduced the number of infections to ten or fewer, averting at least 173
      infections. INTERPRETATION: Early and robust surveillance efforts and case
      finding alone could reduce nascent epidemics. Ensuring access to HIV services and
      harm-reduction interventions could further reduce the likelihood of outbreaks,
      and substantially mitigate their severity and scope. FUNDING: US National
      Institute on Drug Abuse, US National Institutes of Mental Health, US National
      Institutes of Health Big Data to Knowledge programme, and the US National
      Institutes of Health.

PMID- 30220532
TI  - No more Scott Counties.

PMID- 30220535
TI  - [Management of the bladder outlet obstruction associated with BPH in patients
      with special circumstances and/or complications].
AB  - INTRODUCTION: Medical or surgical treatment of lower urinary tract symptoms
      associated with the bladder obstruction due to BPH must take into account
      patient's comorbidities and tBPH complication. The objective is to review the
      different situations in order to optimize the treatment. METHODS: A review of the
      literature was conducted in English on the Pubmed website using the following
      keywords: BPH; diabetes; anticoagulants; antiplatelet agents; renal
      insufficiency; indwelling catheter; bladder calculus; urinary tract infection;
      hematuria; chronic bladder retention or diverticulum. The bibliographical sources
      cited in the European recommendations have been used. RESULTS: Some co
      morbidities and complications may affect surgical outcomes: age is associated
      with increased anesthetic and surgical risks, diabetes with detrusor hypoactivity
      or overactivity that will not always be improved by surgery, chronic bladder
      retention with detrusor underactivity risk and anticoagulants and antiaggregants
      with an additional bleeding risk. Bladder stone should be treated with, in the
      majority of cases, BPH surgery. Bladder diverticulum is an indication of BPH
      surgery but not systematically associated with diverticulectomy. Persistent
      hematuria despite treatment with 5 alpha reductase inhibitor and repeated urinary
      tract infection are indications for surgery. CONCLUSION: The presence of co
      morbidities or complication related to BPH leads to specifics of care that should
      not be ignored urologists. LEVEL OF EVIDENCE: 5 consensus d'experts.

PMID- 30220536
TI  - [How to evaluate BPH-related SBAUs in clinical practice and research?]
AB  - OBJECTIVE: To describe the useful explorations in the clinical evaluation of the
      symptoms of the lower urinary tract symptoms possibly related to BPH (LUTS/BPH),
      and to list the information necessary to allow an evaluation of an instrumental
      or surgical intervention in the treatment of the hypertrophy and benign prostatic
      obstruction. METHOD: Bibliographic research in English using the European,
      American and French recommendations on the evaluation of BPH, supplemented by a
      Pubmed search. RESULTS AND CONCLUSIONS: A number of systematic investigations
      into the evaluation of a man with LUTS/BPH include interrogation, clinical
      examination with rectal examination, urinalysis, flowmeter and post-micturition
      residual volume. The voiding catalog is necessary to understand the mechanism of
      a nocturia. PSA has a triple potential of interest: evaluation of the risk of
      progression, evaluation of the prostatic volume and diagnosis of a cancer of the
      prostate. Creatinine is needed only when chronic retention is observed and before
      surgery. Urethrocystoscopy is essential in case of hematuria, suspicion of
      stenosis of the urethra or bladder tumor. Ultrasound for evaluation of prostate
      volume is essential before surgery, and may be helpful in guiding the decision to
      prescribe a 5 alpha reductase inhibitor. No non-invasive technique has proven its
      possible substitution for pressure flow studies when indicated. When a researcher
      is considering evaluating a surgical or instrumental treatment for BPH,
      preoperative, perioperative and follow-up parameters are expected from readers to
      get a fair idea of the technique being evaluated. LEVEL OF EVIDENCE 5: Consensus
      d'experts.

PMID- 30220537
TI  - Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and
      analysis of published evidence.
AB  - There is limited evidence relating to the impact of disease modifying anti
      rheumatic drugs (DMARDs) upon male fertility and peri-conception paternal
      exposure in men with rheumatic disease. Therefore, we conducted a systematic
      review of available evidence to update information on this subject and guide
      paternal counselling. A systematic search of PubMed and Embase was carried out up
      to September 2017, to find relevant peer-reviewed papers, using keywords for
      fertility/spermatogenesis/conception, men, and disease modifying or biologic
      drugs commonly prescribed in patients with rheumatic disease. The search yielded
      724 papers, and the titles/abstracts were screened independently by 2 authors,
      duplicates removed and 233 potentially relevant papers selected for full text
      review. A total of 84 papers were included in the final analysis which covered
      the impact on fertility of over 611 male exposures to relevant drugs, and over
      5986 pregnancies conceived during paternal exposure to (or within 3 months of
      stopping) these drugs. Aside from the known adverse impact of cyclophosphamide
      and sulfasalazine on spermatogenesis, overall there was no firm evidence of harm
      to fertility or pregnancy outcomes with paternal exposure to anti-TNF therapies,
      abatacept, rituximab, azathioprine, cyclosporine A, hydroxychloroquine,
      leflunomide, methotrexate or mycophenolate mofetil. There was no evidence found
      pertaining to the effects of male exposure to IVIG, tacrolimus, golimumab,
      anakinra or belimumab on fertility or pregnancy outcomes. These results provide
      further reassurance as to the safety of many DMARDs for men trying to conceive
      and will be useful when counselling men about risks of anti-rheumatic drugs to
      fertility and pregnancies, and following accidental conception.

PMID- 30220538
TI  - The specificity of SPECT-CT for the diagnosis of discogenic pain: implications
      for the future of the lumbar fusion outcome score (LUFOS).

PMID- 30220539
TI  - Intraoperative and postoperative analgesia technique following posterior iliac
      crest bone graft harvesting in spine surgery: a closer look.

PMID- 30220540
TI  - It is time to remove the stigma from glial scars: re: Lentivirus-mediated
      silencing of the CTGF gene suppresses the formation of glial scar tissue in a rat
      model of spinal cord injury.

PMID- 30220541
TI  - Resonant Soft X-Ray Scattering Provides Protein Structure with Chemical
      Specificity.
AB  - We introduce resonant soft X-ray scattering (RSoXS) as an approach to study the
      structure of proteins and other biological molecules in solution. Scattering
      contrast calculations suggest that RSoXS has comparable or even higher
      sensitivity than hard X-ray scattering because of contrast generated at the
      absorption edges of constituent elements, such as carbon and oxygen. Here, we
      demonstrate that working near the carbon edge reveals the envelope function of
      bovine serum albumin, using scattering volumes of 10-5 MUL that are multiple
      orders of magnitude lower than traditional scattering experiments. Furthermore,
      tuning the X-ray energy within the carbon absorption edge provides different
      signatures of the size and shape of the protein by revealing the density of
      different types of bonding motifs within the protein. The combination of chemical
      specificity, smaller sample size, and enhanced X-ray contrast will propel RSoXS
      as a complementary tool to existing techniques for the study of biomolecular
      structure.

PMID- 30220542
TI  - An Ion-Permeable State of the Glycine Receptor Captured by Molecular Dynamics.
AB  - Glycine receptors (GlyR) mediate fast inhibitory neurotransmission by switching
      between discrete states in response to ligand-binding events. Recent high
      resolution structures from cryoelectron microscopy (cryo-EM) and X-ray
      crystallography have provided atomistic models for the open and closed states.
      Notably, the cryo-EM structure in complex with glycine illuminated a previously
      unreported wide-open state, whose physiological significance is debated. Here, we
      present the structure of an ion-conducting state of GlyR alpha1 captured by
      molecular dynamics and validate its physiological relevance with computational
      electrophysiology and polyatomic anion permeation simulations. Our analysis
      suggests that none of the experimental structures is a true representation of the
      physiologically active state, although previously characterized open channels in
      GLIC at pH 4, or GluCl/GlyR with ivermectin bound, provide reasonable models.
      These results open the door to an original functional annotation and support the
      conclusion that pore closing by desensitization versus deactivation involves the
      reorientation of the pore-lining helices in opposite directions.

PMID- 30220543
TI  - Probing the Architecture of a Multi-PDZ Domain Protein: Structure of PDZK1 in
      Solution.
AB  - The scaffolding protein PDZK1 has been associated with the regulation of membrane
      transporters. It contains four conserved PDZ domains, which typically recognize a
      3-5-residue long motif at the C terminus of the binding partner. The atomic
      structures of the individual domains are available but their spatial arrangement
      in the full-length context influencing the binding properties remained elusive.
      Here we report a systematic study of full-length PDZK1 and deletion constructs
      using small-angle X-ray scattering, complemented with biochemical and functional
      studies on PDZK1 binding to known membrane protein partners. A hybrid modeling
      approach utilizing multiple scattering datasets yielded a well-defined, extended,
      asymmetric L-shaped domain organization of PDZK1 in contrast to a flexible "beads
      on-string" model predicted by bioinformatics analysis. The linker regions of
      PDZK1 appear to play a central role in the arrangement of the four domains
      underlying the importance of studying scaffolding proteins in their full-length
      context.

PMID- 30220544
TI  - [ENT benign lesions and pseudo-tumors: Case No. 7].

PMID- 30220545
TI  - RhoA protects the podocytes against high glucose-induced apoptosis through YAP
      and plays critical role in diabetic nephropathy.
AB  - BACKGROUND: Podocyte apoptosis is important mechanism that leading to proteinuria
      in Diabetic nephropathy (DN), but the underling mechanisms that cause podocyte
      apoptosis in DN are not very clear. We have recently demonstrated that RhoA, a
      small GTPase protein, effectively protected podocyte apoptosis induced by LPS and
      ADR in vitro. However, the potential role of RhoA in DN is unknown. METHODS AND
      RESULTS: Conditionally immortalized mouse podocyte cells, C57BL/KsJ, db/db
      diabetic mice, and renal biopsies from patients with DN were used for study. The
      treatment of podocytes with high glucose (HG) for 48h significantly induced cell
      apoptosis and decreased RhoA expression and its activity. The expression of RhoA
      was also decreased in glomerular podocytes of db/db mice and patients with DN.
      Knockdown of RhoA by siRNA contributed in the apoptosis of podocyte and induced
      proteinuria in db/db mice. Beyond the increased pro-apoptotic Bax and the
      decreased anti-apoptotic Bcl-2, RhoA knockdown also inhibited the expression of a
      nuclear protein of YAP in podocyte. Over expression active form of YAP completely
      abolished the apoptosis of podocyte induced by RhoA knockdown. CONCLUSION: RhoA
      plays a critical role in DN probably by mediating the podocyte apoptosis through
      YAP. RhoA may be a novel molecular target for the treatment of DN.

PMID- 30220546
TI  - How the S-ICD (subcutaneous implantable cardiac defibrillator) senses cardiac
      signals to minimize cardiac over-sensing and maximize rhythm discrimination.
AB  - Transvenous Implantable Cardioverter Defibrillator (TV-ICD) and subcutaneous ICD
      (S-ICD) devices are available for patients at risk of sudden cardiac death (SCD).
      Both devices sense ventricular arrhythmias with near 100% sensitivity (Gold et
      al., 2012) and have similar rates of inappropriate shocks (IAS) (2.5-4.8%). IAS
      due to supraventricular tachycardias (SVT) is higher for TV-ICDs and IAS due to
      cardiac over-sensing is higher for S-ICDs (Basu-Ray et al., 2017). The S-ICD's
      sensing signal is morphologically rich, resembling the surface electrocardiogram
      (ECG) signal. As such, correlation waveform analysis (CWA) is used by the S-ICD
      to compare the morphology of two signals to minimize S-ICD cardiac over-sensing
      and rhythm discrimination errors. Early experience showed that the S-ICD had a
      comparable overall incidence of IAS compared to TV-ICDs. Progressive improvements
      in S-ICD algorithms and programming strategies have resulted in overall IAS rate
      reduction to 4.3% (Theuns et al., 2018), substantiating the S-ICD as a viable
      choice for patients at risk of SCD.

PMID- 30220547
TI  - Corrigendum to "Efficacy and safety of biologics targeting IL-17 and IL-23 in the
      treatment of moderate-to-severe plaque psoriasis: A systematic review and meta
      analysis of randomized controlled trials" [Int. Immunopharmacol. 62 (2018) 46
      58].

PMID- 30220548
TI  - Production and validation of a polyclonal serum against bovine FSH receptor.
AB  - In ovarian granulosa cells, follicle-stimulating hormone (FSH) regulates the
      proliferation and differentiation events required for follicular growth and
      oocyte maturation. FSH actions are mediated exclusively through the FSH receptor
      (FSHR). In cattle, the FSHR gene expression pattern during folliculogenesis and
      the implications of this receptor in reproductive disorders have been extensively
      studied. However, the limited availability of specific antibodies against bovine
      FSHR has restricted FSHR protein analysis. In the present study, we developed an
      anti-FSHR polyclonal serum by using a 14-kDa peptide conjugated to maltose
      binding protein. The antiserum obtained was characterized by western blot of
      protein extracts from bovine follicles, BGC-1 cells and primary cultures of
      granulosa cells stimulated with testosterone. Also, the blocking effect of serum
      on estradiol secretion and cell viability after gonadotropin stimulus was
      characterized in a functional in vitro assay. A 76-kDa protein, consistent with
      the predicted molecular size of full-length FSHR, was detected in ovarian tissue.
      Besides, two immunoreactive bands of 60-kDa and 30-kDa (only in cultured cells)
      were detected. These bands would be related to some of the isoforms of the
      receptor. Therefore, immunohistochemical assays allowed detecting FSHR in the
      cytoplasm of granulosa cells and an increase in its expression as follicles
      progressed from primordial to large preantral follicles. These results suggest
      that the anti-FSHR serum here developed has good reactivity and specificity
      against the native FSHR. Therefore, this antiserum may serve as a valuable tool
      for future studies of the biological function of FSHR in physiological conditions
      as well as of the molecular mechanism and functional involvement of FSHR in
      reproductive disorders.

PMID- 30220549
TI  - The effect of lipopolysaccharide on anti-inflammatory and pro-inflammatory
      cytokines production of human amniotic epithelial cells.
AB  - Intrauterine infection is a major cause of immune imbalance at the maternal-fetal
      interface, which leads to spontaneous abortion, premature rupture of the fetal
      membranes, and preterm birth. Human amniotic epithelial cells (hAECs) play a
      fundamental role in the maintenance of pregnancy. We hypothesize that bacteria
      influence the immunomodulatory effects of hAECs through stimulation of Toll-like
      receptors (TLRs). Here, we investigated how lipopolysaccharide (LPS) as a
      bacterial component affects anti-inflammatory and pro-inflammatory cytokines
      production of hAECs. Human placentas were obtained from six healthy pregnant
      women and hAECs were isolated. The phenotypic characteristics of hAECs were
      determined by flow cytometry. The hAECs (4 * 105 cells/ml) were cultured in the
      presence or absence of LPS (5 MUg/ml). The viability of the cells was assessed
      and culture supernatants of hAECs were collected after 24, 48 and 72 h of
      incubation. The levels of transforming growth factor-beta1 (TGF-beta1),
      interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-alpha), interleukin-17 A
      (IL-17A), and interferon-gamma (IFN-gamma) were measured by ELISA. Our data
      showed that LPS treatment did not affect the viability of hAECs, while had a
      stimulatory effect on TGF-beta1 production of hAECs (p < 0.001). A significant
      reduction in IL-4 production of LPS-stimulated hAECs was observed (p < 0.05). LPS
      enhanced the production of TNF-alpha and IL-17 A of hAECs (p < 0.05-0.0001). The
      IFN-gamma level was only detectable in two culture supernatants of hAECs, and the
      level was unchanged after stimulation with LPS. Based on these findings, LPS may
      play a pivotal role in immune imbalance at the feto-maternal interface through
      affecting anti-inflammatory and pro-inflammatory cytokines production of hAECs.

PMID- 30220550
TI  - Voltages up to 600V did not affect cryopreserved bovine spermatozoa on capillary
      type electroporation.
AB  - Physical methods such as electroporation have been used to improve the DNA uptake
      efficiency of sperm cells. This study aims to develop an efficient capillary-type
      electroporation method for incorporation of exogenous DNA into bovine
      cryopreserved sperm cells with minimal detrimental effects for later use in SMGT.
      Electroporation of the samples was performed in 2 different groups (with 1 MUg of
      DNA and without DNA transfection) and under five different voltages: 500 V, 600
      V, 700 V, 800 V and 900 V. Non-electroporated sperm cells (with and without DNA)
      were used as control. Kinetics parameters were determined using computer assisted
      semen analyses, whereas membrane integrity, fluidity, mitochondrial function and
      DNA uptake were evaluated by flow cytometry. Results revealed that all tested
      voltages reduced electroporated sperm motility (P < 0.05) when compared to the
      control (non-electroporated cells). Mitochondrial function results showed no
      statistical difference among groups. Similarly, groups electroporated with lower
      (500 V, 600 V and 700 V) voltages showed no difference in cell membrane integrity
      and fluidity. Groups electroporated at higher voltages (800 V and 900 V)
      demonstrated negative effects in cells membrane integrity when compared to other
      groups and control. Also, all electroporated groups demonstrated significant
      higher percentages of transfected sperm cells when compared to the control group
      (P < 0.05). Under the recommendation of using voltages up to 600 V, this method
      represents a safe and efficient alternative for electroporation of bovine
      spermatozoa.

PMID- 30220552
TI  - Administrative costs in health care-A scoping review.
AB  - BACKGROUND: Administrative costs (AC) are a relevant spending category in health
      care, and several approaches exist on how to define and measure them. Based on
      available AC studies, this paper aims to provide a map for this multifaceted
      research topic. METHODS: A scoping review was conducted using the databases
      MEDLINE, EconLit, and Business Source Premier. Literature was screened focussing
      on the research question: What is known about the methodology of AC research from
      scientific publications? RESULTS: Definition concepts mostly rely on national
      cost documentations. The international cost reporting framework of the Systems of
      Health Accounts was a critical reference point in six studies. Indications on how
      to operationalise AC independently from periodical cost reports were suggested by
      ten publications. In this context, time and full time equivalents are the most
      common cost measurements. CONCLUSIONS: The results indicate a lack of evidence
      regarding patients' perceptions of administrative issues in health care. Also,
      research on administrative impact on working conditions for health care employees
      beyond hospitals and physicians' offices is underrepresented. A systematic
      approach to reporting AC studies is needed. Reporting should include the
      appointment of entities actually empowered to change administrative resource
      usage. This would help to promote principles of a balanced administration.

PMID- 30220551
TI  - Replacement costs of cold storage equipment for medical products of public
      healthcare establishments of European Union countries.
AB  - This study presents a quantification of the financial needs to maintain the stock
      of cold equipment for the preservation of medical products in public health care
      establishments of European Union (EU) countries. The conditions that must be
      guaranteed, the types of equipment used, the installed capacity, the total annual
      financial needs and the estimate of its evolution in the near future are
      addressed. A field survey involving Portuguese establishments of various types
      and dimensions was performed in order to assess the currently installed volume by
      type of equipment. Through an analysis based on possible scenarios and using a
      methodology considered adequate, the financial needs to maintain such equipment
      in operation was estimated for Portugal, for each EU country and for the EU as a
      whole. The economic value of these amounts in 2017 and following years was
      obtained assuming the average price of each type of equipment and considering an
      expected evolution of its value.

PMID- 30220553
TI  - Atypical Protein Kinase C: Breaking Down Barriers in Ocular Disease?
AB  - This commentary highlights the article by Lin et al that demonstrates the
      therapeutic potential of small-molecule atypical protein kinase C inhibitors in
      inflammatory ocular disease.

PMID- 30220555
TI  - Simultaneous acute presentation of generalized chorea and subacute combined
      degeneration secondary to vitamin B12 deficiency.

PMID- 30220554
TI  - Inhibition of Atypical Protein Kinase C Reduces Inflammation-Induced Retinal
      Vascular Permeability.
AB  - Changes in permeability of retinal blood vessels contribute to macular edema and
      the pathophysiology of numerous ocular diseases, including diabetic retinopathy,
      retinal vein occlusions, and macular degeneration. Vascular endothelial growth
      factor (VEGF) induces retinal permeability and macular thickening in these
      diseases. However, inflammatory agents, such as tumor necrosis factor-alpha (TNF
      alpha), also may drive vascular permeability, specifically in patients
      unresponsive to anti-VEGF therapy. Recent evidence suggests VEGF and TNF-alpha
      induce permeability through distinct mechanisms; however, both require the
      activation of atypical protein kinase C (aPKC). We provide evidence, using
      genetic mouse models and therapeutic intervention with small molecules, that
      inhibition of aPKC prevented or reduced vascular permeability in animal models of
      retinal inflammation. Expression of a kinase-dead aPKC transgene, driven by a
      vascular and hematopoietic restricted promoter, reduced retinal vascular
      permeability in an ischemia-reperfusion model of retinal injury. This effect was
      recapitulated with a small-molecule inhibitor of aPKC. Expression of the kinase
      dead aPKC transgene dramatically reduced the expression of inflammatory factors
      and blocked the attraction of inflammatory monocytes and granulocytes after
      ischemic injury. Coinjection of VEGF with TNF-alpha was sufficient to induce
      permeability, edema, and retinal inflammation, and treatment with an aPKC
      inhibitor prevented VEGF/TNF-alpha-induced permeability. These data suggest that
      aPKC contributes to inflammation-driven retinal vascular pathology and may be an
      attractive target for therapeutic intervention.

PMID- 30220557
TI  - Atypical late presentation of BPAN in a male: A case report.

PMID- 30220556
TI  - Benefits and risks of unilateral and bilateral ventral intermediate nucleus deep
      brain stimulation for axial essential tremor symptoms.
AB  - INTRODUCTION: Many experts assume bilateral deep brain stimulation (DBS) is
      necessary to improve axial tremor in essential tremor (ET). In the largest
      clinical trial of DBS for ET to date evaluating a non-directional, constant
      current device, we studied the effects of unilateral and staged bilateral DBS on
      axial tremor. METHODS: We included all participants from the original trial with
      unilateral ventral intermediate nucleus (VIM) DBS and 90-day follow up at
      minimum. Primary outcomes were changes in pooled axial subscores in the Clinical
      Rating Scale for Tremor (CRST) at 90 and 180 days after activation of unilateral
      VIM DBS compared to pre-operative baseline (n=119). Additionally, we performed
      within-subject analyses for unilateral versus bilateral DBS at 180 days in the
      cohort who underwent staged surgery to bilateral DBS (n=39). RESULTS: Unilateral
      VIM DBS improved midline tremor by 58% at 90 days (median[IQR]) (3[3] to 1[2],
      p<0.001) and 65% at 180 days (3[3] to 1[2], p<0.001) versus pre-op baseline. In
      the staged to bilateral DBS cohort, midline tremor scores further improved after
      bilateral DBS at 180 days by 63% versus unilateral DBS (3[3] to 1[3], p=0.007).
      There were, however, 35 additional DBS and surgery-related adverse events, 14
      related to incoordination, gait impairment, or speech impairment, versus 6 after
      unilateral DBS. CONCLUSION: Unilateral VIM DBS for ET significantly improved
      associated axial tremor. Staged bilateral DBS was associated with additional
      axial tremor improvement but also additional adverse events. Unilateral VIM DBS
      may be sufficient to achieve a goal of contralateral limb and axial tremor
      attenuation.

PMID- 30220558
TI  - Phosphorylation of the Ribosomal Protein RPL12/uL11 Affects Translation during
      Mitosis.
AB  - Emerging evidence indicates that heterogeneity in ribosome composition can give
      rise to specialized functions. Until now, research mainly focused on differences
      in core ribosomal proteins and associated factors. The effect of
      posttranslational modifications has not been studied systematically. Analyzing
      ribosome heterogeneity is challenging because individual proteins can be part of
      different subcomplexes (40S, 60S, 80S, and polysomes). Here we develop polysome
      proteome profiling to obtain unbiased proteomic maps across ribosomal
      subcomplexes. Our method combines extensive fractionation by sucrose gradient
      centrifugation with quantitative mass spectrometry. The high resolution of the
      profiles allows us to assign proteins to specific subcomplexes. Phosphoproteomics
      on the fractions reveals that phosphorylation of serine 38 in RPL12/uL11, a known
      mitotic CDK1 substrate, is strongly depleted in polysomes. Follow-up experiments
      confirm that RPL12/uL11 phosphorylation regulates the translation of specific
      subsets of mRNAs during mitosis. Together, our results show that
      posttranslational modification of ribosomal proteins can regulate translation.

PMID- 30220559
TI  - Box C/D snoRNP Autoregulation by a cis-Acting snoRNA in the NOP56 Pre-mRNA.
AB  - Box C/D snoRNAs constitute a class of abundant noncoding RNAs that associate with
      common core proteins to form catalytic snoRNPs. Most of these operate in trans to
      assist the maturation of rRNAs by guiding and catalyzing the 2'-O-methylation of
      specific nucleotides. Here, we report that the human intron-hosted box C/D snoRNA
      snoRD86 acts in cis as a sensor and master switch controlling levels of the
      limiting snoRNP core protein NOP56, which is important for proper ribosome
      biogenesis. Our results support a model in which snoRD86 adopts different RNP
      conformations that dictate the usage of nearby alternative splice donors in the
      NOP56 pre-mRNA. Excess snoRNP core proteins prevent further production of NOP56
      and instead trigger the generation of a cytoplasmic snoRD86-containing NOP56
      derived lncRNA via the nonsense-mediated decay pathway. Our findings reveal a
      feedback mechanism based on RNA structure that controls the precise coordination
      between box C/D snoRNP core proteins and global snoRNA levels.

PMID- 30220560
TI  - Efficient and Accurate Quantitative Profiling of Alternative Splicing Patterns of
      Any Complexity on a Laptop.
AB  - Alternative splicing (AS) is a widespread process underlying the generation of
      transcriptomic and proteomic diversity and is frequently misregulated in human
      disease. Accordingly, an important goal of biomedical research is the development
      of tools capable of comprehensively, accurately, and efficiently profiling AS.
      Here, we describe Whippet, an easy-to-use RNA-seq analysis method that rapidly
      with hardware requirements compatible with a laptop-models and quantifies AS
      events of any complexity without loss of accuracy. Using an entropic measure of
      splicing complexity, Whippet reveals that one-third of human protein coding genes
      produce transcripts with complex AS events involving co-expression of two or more
      principal splice isoforms. We observe that high-entropy AS events are more
      prevalent in tumor relative to matched normal tissues and correlate with
      increased expression of proto-oncogenic splicing factors. Whippet thus affords
      the rapid and accurate analysis of AS events of any complexity, and as such will
      facilitate future biomedical research.

PMID- 30220561
TI  - LncRNA CamK-A Regulates Ca2+-Signaling-Mediated Tumor Microenvironment
      Remodeling.
AB  - Cancer cells entail metabolic adaptation and microenvironmental remodeling to
      survive and progress. Both calcium (Ca2+) flux and Ca2+-dependent signaling play
      a crucial role in this process, although the underlying mechanism has yet to be
      elucidated. Through RNA screening, we identified one long noncoding RNA (lncRNA)
      named CamK-A (lncRNA for calcium-dependent kinase activation) in tumorigenesis.
      CamK-A is highly expressed in multiple human cancers and involved in cancer
      microenvironment remodeling via activation of Ca2+-triggered signaling.
      Mechanistically, CamK-A activates Ca2+/calmodulin-dependent kinase PNCK, which in
      turn phosphorylates IkappaBalpha and triggers calcium-dependent nuclear factor
      kappaB (NF-kappaB) activation. This regulation results in the tumor
      microenvironment remodeling, including macrophage recruitment, angiogenesis, and
      tumor progression. Notably, our human-patient-derived xenograft (PDX) model
      studies demonstrate that targeting CamK-A robustly impaired cancer development.
      Clinically, CamK-A expression coordinates with the activation of CaMK-NF-kappaB
      axis, and its high expression indicates poor patient survival rate, suggesting
      its role as a potential biomarker and therapeutic target.

PMID- 30220563
TI  - Custom CAD/CAM implants for complex craniofacial reconstruction in children: Our
      experience based on 136 cases?.
AB  - BACKGROUND: CAD-CAM patient-specific implants offer cerebral protection and
      improved facial balance without the disadvantages of autologous bone grafting
      such as donor site morbidity and unpredictable resorption. Several alloplastic
      materials are available, but titanium, polymethylmethacrylate (PMMA), and
      polyetheretherketone (PEEK) are the current popular choices. We reviewed our
      experience of applying different alloplastic CAD-CAM materials in the
      reconstruction of complex pediatric craniofacial deformities. METHODS: A
      retrospective review was performed of all pediatric patients who underwent a
      complex inlay or onlay implant craniofacial reconstruction using CAD-CAM PEEK,
      PMMA, or titanium implants at a single institution. Demographics, cost, operative
      time, complications, and outcomes were assessed. RESULTS: Between 2003 and 2014,
      136 patients (69 male; 67 female; mean age 11.5 years (3-22 years); mean follow
      up 30 months) had custom patient-specific craniofacial reconstruction with PEEK
      (n = 72), PMMA (n = 42), and titanium (n = 22) implants (inlay = 93; onlay = 43).
      Indications included congenital anomalies (26.5%), decompressive craniectomies
      (25.0%), craniofacial syndromes (25.7%), tumor defects (14.0%), and post-trauma
      (6.6%). Implant cost varied significantly for PEEK ($7703 CAD) and PMMA ($8328
      CAD) compared with that for titanium ($11,980 CAD) (p < 0.0005). Six patients
      (4.4%) required surgery due to infection consisting of irrigation and antibiotic
      administration with successful implant salvage in three patients. All infections
      occurred in the PEEK group. Five patients (3.7%) ultimately had implants removed
      due to infection (n = 3), late exposure (titanium; n = 1), or late fracture
      (PMMA; n = 1). CONCLUSIONS: CAD-CAM alloplast reconstruction in the management of
      complex pediatric craniofacial deformities is effective although expensive.
      Implant infection does not always require explantation. A reconstruction
      algorithm is presented.

PMID- 30220564
TI  - Inferior portion of the perpendicular plate of the ethmoid as a suitable grafting
      material in rhinoplasty and septoplasty procedures.

PMID- 30220562
TI  - Structures of the Human PGD2 Receptor CRTH2 Reveal Novel Mechanisms for Ligand
      Recognition.
AB  - The signaling of prostaglandin D2 (PGD2) through G-protein-coupled receptor
      (GPCR) CRTH2 is a major pathway in type 2 inflammation. Compelling evidence
      suggests the therapeutic benefits of blocking CRTH2 signaling in many
      inflammatory disorders. Currently, a number of CRTH2 antagonists are under
      clinical investigation, and one compound, fevipiprant, has advanced to phase 3
      clinical trials for asthma. Here, we present the crystal structures of human
      CRTH2 with two antagonists, fevipiprant and CAY10471. The structures, together
      with docking and ligand-binding data, reveal a semi-occluded pocket covered by a
      well-structured amino terminus and different binding modes of chemically diverse
      CRTH2 antagonists. Structural analysis suggests a ligand entry port and a binding
      process that is facilitated by opposite charge attraction for PGD2, which differs
      significantly from the binding pose and binding environment of lysophospholipids
      and endocannabinoids, revealing a new mechanism for lipid recognition by GPCRs.

PMID- 30220565
TI  - Comments on "Long-term outcome of patients with or without osseointegrated
      implants after resection of mandibular ameloblastoma and reconstruction with
      vascularized bone graft: Functional assessment and quality of life".

PMID- 30220566
TI  - Ten years of myocutaneous flaps for pressure ulcers in patients with spinal
      lesions: Analysis of complications in the framework of a specialised medical
      surgical pathway.
AB  - INTRODUCTION: The objective of the study is to analyse complications associated
      with surgery for pelvic pressure ulcers in terms of their frequency, nature and
      rate of surgical revisions. The secondary aims are to analyse the rate of
      recurrence, length of stay and time to healing, and to determine factors
      associated with complications and recurrence. METHODS: It is a single-centre,
      retrospective cohort study with a 10-year follow-up setting in Nantes University
      Hospital, France, a specialist centre for spinal cord injury (SCI). All patients
      who were admitted to the Neurological Physical Medicine and Rehabilitation (PMR)
      department for surgery (flap coverage) for pelvic pressure ulcers between 1st of
      January 2004 and 30th September 2014 were included. The main outcome measures
      were the rate of complications, rate of recurrence, length of stay and time to
      healing, as well as factors associated with complications and recurrence.
      RESULTS: One hundred and sixty-six patients underwent 252 flap procedures in 239
      operations. The majority of patients had SCI (78.3%). The ulcer sites were mainly
      ischial (67%), sacral (20%) and trochanteric (12%). Gluteus maximus was used most
      often (75.3% of flaps) (ischial and sacral ulcers), followed by tensor fascia
      lata (16.2%) (trochanteric ulcers). The rate of complications that delayed return
      to wheelchair at 6 weeks was 34.5%. The factors associated with complications
      were more than one surgical ulcer and drainage time greater than 10 days. The
      rate of recurrence was 20.04%. The factors related to recurrence were young age,
      scoliosis and an oblique pelvis. CONCLUSIONS: Management within a specialised
      medical-surgical pathway limited post-operative complications and recurrences in
      this sample of subjects who mostly had SCI.

PMID- 30220567
TI  - The Ciliary Machinery Is Repurposed for T Cell Immune Synapse Trafficking of LCK.
AB  - Upon engagement of the T cell receptor with an antigen-presenting cell, LCK
      initiates TCR signaling by phosphorylating its activation motifs. However, the
      mechanism of LCK activation specifically at the immune synapse is a major
      question. We show that phosphorylation of the LCK activating Y394, despite
      modestly increasing its catalytic rate, dramatically focuses LCK localization to
      the immune synapse. We describe a trafficking mechanism whereby UNC119A extracts
      membrane-bound LCK by sequestering the hydrophobic myristoyl group, followed by
      release at the target membrane under the control of the ciliary ARL3/ARL13B. The
      UNC119A N terminus acts as a "regulatory arm" by binding the LCK kinase domain,
      an interaction inhibited by LCK Y394 phosphorylation, thus together with the
      ARL3/ARL13B machinery ensuring immune synapse focusing of active LCK. We propose
      that the ciliary machinery has been repurposed by T cells to generate and
      maintain polarized segregation of signals such as activated LCK at the immune
      synapse.

PMID- 30220569
TI  - Dietary Lipids Modulate Notch Signaling and Influence Adult Intestinal
      Development and Metabolism in Drosophila.
AB  - Tissue homeostasis involves a complex balance of developmental signals and
      environmental cues that dictate stem cell function. We found that dietary lipids
      control enteroendocrine cell production from Drosophila posterior midgut stem
      cells. Dietary cholesterol influences new intestinal cell differentiation in an
      Hr96-dependent manner by altering the level and duration of Notch signaling.
      Exogenous lipids modulate Delta ligand and Notch extracellular domain stability
      and alter their trafficking in endosomal vesicles. Lipid-modulated Notch
      signaling occurs in other nutrient-dependent tissues, suggesting that Delta
      trafficking in many cells is sensitive to cellular sterol levels. These diet
      mediated alterations in young animals contribute to a metabolic program that
      persists after the diet changes. A low-sterol diet also slows the proliferation
      of enteroendocrine tumors initiated by Notch pathway disruption. Thus, a specific
      dietary nutrient can modify a key intercellular signaling pathway to shift stem
      cell differentiation and cause lasting changes in tissue structure and
      physiology.

PMID- 30220568
TI  - Single Cell and Open Chromatin Analysis Reveals Molecular Origin of Epidermal
      Cells of the Skin.
AB  - How embryonic progenitors coordinate cell fate specification and establish
      transcriptional and signaling competence is a fundamental question in
      developmental biology. Here, we show that transcription factor DeltaNp63
      profoundly changes the transcriptome and remodels thousands of open chromatin
      regions of Krt8+ progenitors during epidermal fate specification. ATAC-seq and
      single-cell RNA-seq reveal that DeltaNp63-dependent programs govern epidermal
      lineage formation, and DeltaNp63-independent programs, mediated by AP2 and AP1
      transcription factors, promote epidermal differentiation and epithelial-to
      mesenchymal transition. DeltaNp63 promotes Wnt signaling by directly upregulating
      Wnt ligands, Frizzled receptors, and transcription factors. Deletion of beta
      catenin in Krt8+ progenitors delays their maturation into Krt5+ progenitors. The
      lack of epidermal Wnt production in the absence of DeltaNp63 also incapacitates
      Wnt activation in the underlying dermal cells. These findings reveal the
      remarkable changes of the transcriptome, open chromatin, and signaling pathways
      at the onset of skin development and uncover the molecular cascade for epidermal
      lineage formation.

PMID- 30220570
TI  - Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to
      Nutrient Content.
AB  - The intestine is an organ with an exceptionally high rate of cell turnover, and
      perturbations in this process can lead to severe diseases such as cancer or
      intestinal atrophy. Nutrition has a profound impact on intestinal volume and
      cellular architecture. However, how intestinal homeostasis is maintained in
      fluctuating dietary conditions remains insufficiently understood. By utilizing
      the Drosophila midgut model, we reveal a novel stem cell intrinsic mechanism
      coupling cellular metabolism with stem cell extrinsic growth signal. Our results
      show that intestinal stem cells (ISCs) employ the hexosamine biosynthesis pathway
      (HBP) to monitor nutritional status. Elevated activity of HBP promotes Warburg
      effect-like metabolic reprogramming required for adjusting the ISC division rate
      according to nutrient content. Furthermore, HBP activity is an essential
      facilitator for insulin signaling-induced ISC proliferation. In conclusion, ISC
      intrinsic hexosamine synthesis regulates metabolic pathway activities and defines
      the stem cell responsiveness to niche-derived growth signals.

PMID- 30220572
TI  - Clinical Evaluation, Imaging, and Management of Adolescent Idiopathic and Adult
      Degenerative Scoliosis.
AB  - We provide a comprehensive review of the clinical presentation, imaging
      evaluation, classification, and management of adolescent idiopathic and adult
      degenerative scoliosis.

PMID- 30220573
TI  - Corrigendum to 'Visual Pathway Injuries in Pediatric Ocular Trauma - A Survey of
      the National Trauma Data Bank from 2008-2014' [Pediatric Neurology 85 (2018) 43
      50].

PMID- 30220571
TI  - RAB-35 and ARF-6 GTPases Mediate Engulfment and Clearance Following Linker Cell
      Type Death.
AB  - Clearance of dying cells is essential for development and homeostasis. Conserved
      genes mediate apoptotic cell removal, but whether these genes control non
      apoptotic cell removal is a major open question. Linker cell-type death (LCD) is
      a prevalent non-apoptotic developmental cell death process with features
      conserved from C. elegans to vertebrates. Using microfluidics-based long-term in
      vivo imaging, we show that unlike apoptotic cells, the C. elegans linker cell,
      which dies by LCD, is competitively phagocytosed by two neighboring cells,
      resulting in cell splitting. Subsequent cell elimination does not require
      apoptotic engulfment genes. Rather, we find that RAB-35 GTPase is a key
      coordinator of competitive phagocytosis onset and cell degradation. RAB-35 binds
      CNT-1, an ARF-6 GTPase activating protein, and removes ARF-6, a degradation
      inhibitor, from phagosome membranes. This facilitates phosphatidylinositol-4,5
      bisphosphate removal from phagosome membranes, promoting phagolysosome
      maturation. Our studies suggest that RAB-35 and ARF-6 drive a conserved program
      eliminating cells dying by LCD.

PMID- 30220574
TI  - Detrended fluctuation analysis detects altered coordination of running gait in
      athletes following a heavy period of training.
AB  - OBJECTIVES: To investigate whether functional overreaching affects locomotor
      system behaviour when running at fixed relative intensities and if any effects
      were associated with changes in running performance. DESIGN: Prospective
      intervention study. METHODS: Ten trained male runners completed three training
      blocks in a fixed order. Training consisted of one week of light training
      (baseline), two weeks of heavy training designed to induce functional
      overreaching, and ten days of light taper training designed to allow athletes to
      recover from, and adapt to, the heavy training. Locomotor behaviour, 5-km time
      trial performance, and subjective reports of training status (Daily Analysis of
      Life Demands for Athletes (DALDA) questionnaire) were assessed at the completion
      of each training block. Locomotor behaviour was assessed using detrended
      fluctuation analysis of stride intervals during running at speeds corresponding
      to 65% and 85% of maximum heart rate (HRmax) at baseline. RESULTS: Time trial
      performance (effect size +/-95% confidence interval (ES): 0.16+/-0.06; p<0.001),
      locomotor behaviour at 65% HRmax (ES: -1.12+/-0.95; p=0.026), and DALDA (ES:
      2.55+/-0.80; p<0.001) were all detrimentally affected by the heavy training. Time
      trial performance improved relative to baseline after the taper (ES: -0.16+/
      0.10; p=0.003) but locomotor behaviour at 65% HRmax (ES: -1.18+/-1.17; p=0.048)
      and DALDA (ES: 0.92+/-0.90; p=0.045) remained impaired. CONCLUSIONS: Locomotor
      behaviour during running at 65% HRmax was impaired by functional overreaching and
      remained impaired after a 10-day taper, despite improved running performance.
      Locomotor changes may increase injury risk and should be considered within
      athlete monitoring programs independently of performance changes.

PMID- 30220575
TI  - Three-dimensional reconstruction of the temporal bone: Comparison of in situ, CT,
      and CBCT measurements.
AB  - OBJECTIVE: To evaluate the accuracy of three-dimensional (3D) Cone Beam Computed
      Tomography (CBCT) and Computed Tomography (CT) reconstructions of human temporal
      bones compared with in situ measurements. MATERIAL AND METHODS: Experimental
      anatomical study of 10 human temporal bones. Wilcoxon's test was used to compare
      8 distances on each temporal bone measured in situ and then on 3D CT and CBCT
      reconstructions. Six landmarks were used: external auditory canal (EAC), tip of
      the mastoid process, tip of the occiput, zygoma, a point situated 1cm above the
      tip of the mastoid process (T0) (open technique: lower limit of the
      mastoidectomy), head of stapes. RESULTS: No significant difference was observed
      between the 3 measuring techniques for any of the distances studied (P>0.05).
      DISCUSSION: This study demonstrates the equivalence of CBCT and CT for temporal
      bone measurements. CONCLUSION: CBCT is a new imaging modality providing 3D
      reconstructions of the temporal bone that are as reliable as those obtained by
      CT. As a result of better spatial resolution compared to CT, CBCT is associated
      with a significantly lower radiation dose. This technique constitutes a
      morphological progress, as CBCT is comparable to CT, allowing investigation of
      pathological ears with a lower radiation dose.

PMID- 30220576
TI  - Effect of an in-situ simulation workshop on home birth practice in Australia.
AB  - PROBLEM: Interprofessional training programs for obstetric emergencies have been
      introduced for up-skilling birth unit staff in hospitals but not frequently used
      in training midwives and paramedicine staff for home birth emergency. BACKGROUND:
      Practical Obstetric Multiprofessional Training (PROMPT) has previously been
      described in the home birth setting using in-situ simulation training of home
      births for midwifery and paramedicine staff. AIM: The aim of this study was to
      evaluate the benefit of the home birth simulation in clinical practice and to
      explore how the simulation program prepared the midwives for a birth-related
      emergency in a publicly funded home birth program. METHODS: Midwives conducting
      home births, the midwifery educator and the simulated woman in labour (n=9)
      attended an interview that explored how the midwives' learning through simulation
      affected their home birth clinical practice. The simulated woman and the
      facilitator who conducted the simulation for more than six years were also
      interviewed to comment on the observed change in performance in simulation. The
      interview transcripts were thematically analysed. FINDINGS: The themes that were
      identified and agreed upon, were applying learning to clinical practice, learning
      in teams, valuing realism, facilitating simulation based education and managing
      variation. DISCUSSION: In-situ nature of simulation with home birth midwives and
      paramedical staff facilitated learning transfer and team-based approach to
      practice. The careful simulation design provided a breadth of experience in
      emergencies. CONCLUSION: Applying learning to prepare for clinical emergency
      situations changed the midwives' approach in managing home births. This provided
      evidence for a change in behaviour (Level 3 Kirkpatrick's framework) and transfer
      of learning, leading to changed protocols (Level 4a Kirkpatrick's framework).

PMID- 30220577
TI  - Becoming a midwife: A survey study of midwifery alumni.
AB  - BACKGROUND: Becoming a competent midwife is a complex process. The aim of
      midwifery education is to support the development of competence in midwifery
      skills, knowledge and to prepare graduates to meet the responsibilities inherent
      in the midwifery role. AIM: To explore the experiences of our alumni midwives,
      ask how well they perceived their midwifery programme had prepared them for
      beginning midwifery practice and to identify any curriculum changes, or
      postgraduate study topics, that would support the transition to midwifery
      practice. METHODS: An online survey was conducted with alumni of a Bachelor of
      Midwifery programme (New Zealand) who graduated between 2011 and 2014. The
      quantitative data were analysed using descriptive statistics, and a general
      inductive approach was used to develop themes from the qualitative data in the
      comment boxes. FINDINGS: Forty-two alumni viewed becoming a midwife as a
      blend/combination of: (1) gaining the knowledge and practical skills required for
      the profession; (2) management skills in areas of running a business, working
      with other people, navigating local procedures and processes effectively, and
      balancing work with personal life; (3) gaining confidence in one's competence,
      and (4) having support along the way. DISCUSSION: Competence in current evidence
      based midwifery knowledge and practice is important in educating midwifery
      students. However, to transition to practice, a supportive environment is needed
      to assist midwives to develop self-management, business skills, and the
      confidence to negotiate and collaborate with colleagues and other health
      professionals. CONCLUSIONS: Not only did midwifery knowledge and practice skills
      matter for alumni, but also the acquisition of management skills, strategies for
      building confidence, and ongoing support. Content that facilitates these
      requirements should be included in midwifery programmes to support the transition
      from student to practitioner.

PMID- 30220578
TI  - The Open Insulin Project: A Case Study for 'Biohacked' Medicines.
AB  - New innovation ecosystems are emerging that challenge the complex intellectual
      property and regulatory landscape surrounding drug development in the United
      States (US). A prime example is an initiative known as the Open Insulin Project.
      The goal of the project is to sidestep patents and enable generic manufacturers
      to produce cheaper insulin. However, the US regulatory environment, not patent
      exclusivity, is the main barrier to insulin affordability. If the Open Insulin
      Project succeeds in releasing an open protocol for insulin manufacturing, follow
      on work could enable a number of new insulin production ecosystems, including
      'home-brewed' insulin. Regulators will need to consider how to proceed in a
      future where commercial pharmaceuticals remain unaffordable, but patients are
      empowered to produce drugs for their personal use.

PMID- 30220579
TI  - Cost-effectiveness of EGCRISC application versus hepatitis C virus mass screening
      in Egypt.
AB  - BACKGROUND: The Egyptian model of care against hepatitis C virus (HCV) has a
      great success in treatment and treatment accessibility, but still screening
      efforts must be strengthened. HCV is a silent infection when most of infected
      people are unaware of their infection. EGCRISC is a newly developed and validated
      risk-based HCV screening tool in Egypt that has shown a considerably good
      performance but is still underused. This brief communication is to analyze its
      use cost-effectiveness versus mass screening. STUDY DESIGN: Mathematical
      comparative analysis for economic evaluation. METHODS: Its performance data as
      published recently were used, and a minimum cost of L.E. 20 was considered per
      one antibody testing. The 2015 health issue survey and population census were
      used for estimating the population, infected individuals and susceptibles.
      RESULTS: The analysis showed that using EGCRISC would save LE 0.43 billion
      accounting for about 21,646,227 unnecessary tests, while missing less than 70,000
      cases when compared to mass screening. CONCLUSION: EGCRISC is a cost-effective
      tool that must be adopted nationwide as soon as possible in Egypt for the best
      outcome of HCV control.

PMID- 30220580
TI  - WNT Signaling in Cancer Immunosurveillance.
AB  - Deregulated WNT signaling has been shown to favor malignant transformation, tumor
      progression, and resistance to conventional cancer therapy in a variety of
      preclinical and clinical settings. Accumulating evidence suggests that aberrant
      WNT signaling may also subvert cancer immunosurveillance, hence promoting
      immunoevasion and resistance to multiple immunotherapeutics, including immune
      checkpoint blockers. Here, we discuss the molecular and cellular mechanisms
      through which WNT signaling influences cancer immunosurveillance and present
      potential therapeutic avenues to harness currently available WNT modulators for
      cancer immunotherapy.

PMID- 30220581
TI  - Kinesin-5 Regulation and Function in Mitosis.
AB  - Chromosome segregation during cell division requires a bipolar mitotic spindle.
      Therefore, how the spindle is formed, maintained, and functions is of fundamental
      importance for all eukaryotic cells. Members of the evolutionarily conserved
      kinesin-5 family of motor proteins have been shown to play an essential role in
      spindle formation by generating forces that establish and maintain spindle
      bipolarity and contribute to spindle elongation. Recent work demonstrates that
      accessory proteins and post-translational modifications regulate the localization
      and activity of kinesin-5 motors in cells. In addition, some kinesin-5 motors can
      move toward the microtubule plus-or-minus end. This new information provides
      insight into how these motors function during mitosis.

PMID- 30220582
TI  - Determinants of fracture in adults with type 1 diabetes in the USA: Results from
      the T1D Exchange Clinic Registry.
AB  - AIMS: To examine the prevalence/determinants of fracture in the T1D Exchange
      Clinic Registry. RESEARCH DESIGN/METHODS: Adults (>=18 years) with T1D duration
      >=5 years, diagnosed before age 45 years completed a fracture questionnaire.
      Additional characteristics were collected from registry data. Only fractures
      reported as occurring after T1D diagnosis were included. Characteristics were
      compared between those with and without fractures. RESULTS: Respondents included
      756 adults (mean age 39 +/- 16 years, 28% >=50 years, 63% female, 90% non
      Hispanic White, diabetes duration 24 +/- 14 years); 48% reported >=1 fracture
      since diagnosis. Of the 659 reported fractures, 24% involved metatarsal/toe, 21%
      metacarpal/fingers, 14% fibula/tibia, 5% hip/pelvis/femur and 3% vertebrae. Those
      with fracture were more likely to be older (43 +/- 16 vs. 36 +/- 14 years), have
      longer T1D duration (28 +/- 14 vs. 20 +/- 12 years), been diagnosed with T1D
      before age 20 years (79% vs. 71%) compared to those without fracture (all p
      values < 0.01). CONCLUSIONS: Data from this national sample suggest fractures in
      adults with T1D are common at young age and frequently involve peripheral sites.
      Age, longer diabetes duration, and T1D diagnosis prior to peak bone mass accrual
      are notable risk factors. Further research is needed to examine the impact of
      these determinants on fracture risk in T1D.

PMID- 30220583
TI  - Corrigendum to "A Catalytically-Disabled Double Mutant of Src Tyrosine Kinase Can
      Be Stabilized into an Active-Like Conformation." J. Mol. Biol. 430(6) (Mar 16
      2018), 881-889.

PMID- 30220584
TI  - A Reliability Comparison of Cone-Beam Breast Computed Tomography and Mammography:
      Breast Density Assessment Referring to the Fifth Edition of the BI-RADS Atlas.
AB  - RATIONALE AND OBJECTIVES: To evaluate the reliability of cone-beam breast
      computed tomography (CBBCT) in visual assessment of breast density referring to
      the fifth edition of the Breast Imaging Reporting and Data System compared to
      digital mammography. MATERIALS AND METHODS: Breast density assessments of 130
      female patients were performed by five radiologists referring to the fifth
      edition of Breast Imaging Reporting and Data System atlas both on two-view
      mammograms and CBBCT images. Assessments were repeated by three radiologists with
      different experience more than 1 month after the initial evaluation. The inter-
      and intrareader agreements were compared by using the Cohen's weighted Kappa
      statistic and intraclass correlation coefficient. Weighted Kappa statistic was
      also used to analyze the agreement between CBBCT images and mammograms. The
      influence of radiologist experience for breast density assessment was analyzed
      using a chi-square test. RESULTS: For CBBCT images, the inter-reader agreement
      was 0.781, whereas the agreement on mammograms was 0.744, both demonstrating
      moderate agreement. The level of intrareader reliability was higher on the CBBCT
      images than mammograms for breast density evaluation, 0.856 versus 0.786. Based
      on the majority report, the agreement between these two modalities was on
      substantial agreement degree. There was a statistically significant difference
      among radiologists with different levels of experience, and higher density
      categories were reported more often by experienced reader. CONCLUSION: CBBCT
      showed equal aptitude and better agreement for the breast density evaluation
      compared to mammography. CBBCT could be an effective modality for breast density
      assessment and breast cancer risk evaluation in routine diagnosis and breast
      cancer screening.

PMID- 30220585
TI  - Postoperative MR imaging features after superior semicircular canal plugging in
      Minor syndrome.
AB  - PURPOSE: To report the postoperative magnetic resonance imaging (MRI) features
      after superior semicircular canal plugging in patients with Minor syndrome.
      MATERIALS AND METHODS: The MRI examinations with 3D T2-weighted SPACE sequence of
      12 patients with superior semicircular canal dehiscence syndrome (SCDS) were
      retrospectively assessed. Two radiologists independently evaluated the presence
      of a filling defect of the superior semicircular canal above the superior ampulla
      and the common crus using an oblique plane parallel to the superior semicircular
      canal (Poschl's plane). RESULTS: Postoperative MRI showed a filling defect above
      the ampulla of the superior semicircular canal and the common crus in 8/12
      patients (67%). Three patients (3/12; 25%) had a filling defect involving also
      the superior ampulla that caused postoperative labyrinthitis with labyrinthine
      enhancement on MRI in 2 patients. One patient (1/12; 8%) had incomplete plugging
      of superior semicircular canal with abnormal functional tests and remaining
      symptoms. CONCLUSION: Postoperative MRI shows a normal plugging aspect of the
      superior semicircular canal in 67% of patients. MRI can reveal complications that
      may have therapeutic implications.

PMID- 30220586
TI  - MR imaging of cystic ovarian teratoma with internal floating globules.

PMID- 30220587
TI  - Response to comments on "Volvulus of the sigmoid colon is associated with
      hypotrophy of the left lateral segment of the liver and the absence of sigmoid
      diverticulum".

PMID- 30220588
TI  - Percutaneous gastric tube placement: Comparison of trans-abdominal and trans-oral
      approach in patients with chronic ascites.
AB  - PURPOSE: The purpose of this study was to compare the trans-abdominal (TA) and
      trans-oral (TO) approaches for fluoroscopic-guided gastrostomy tube placement in
      patients with chronic ascites. MATERIALS AND METHODS: A 10-year review of
      clinical imaging and medical records at a single institution identified 29
      patients with chronic recurrent ascites who underwent gastrostomy (GT) or gastro
      jejunostomy tube (GJT) placement. In 22 patients (18 women, 4 men) aged from 22
      to 76 years of age (mean age, 57.7+/-13.1 years), a GT or GJT was placed with the
      TO approach, and in 7 (7 women) from 31 to 86 years of age (mean age, 63+/-16.8
      years) with the TA approach. RESULTS: Technical success was 100% in both groups
      with one (1/22; 5%) immediate complication in the TO group. Fluoroscopy time was
      significantly greater in the TO group (P=0.002). Leakage of ascites was
      significantly more frequent in the TA group (P=0.04). There was no significant
      difference in bleeding or inflammation (P=0.14 and P=0.43, respectively). The
      cumulative tract related complication rate was significantly greater in the TA
      group (P=0.03). CONCLUSION: Fluoroscopy times and the overall incidence of tract
      related complications, in particular leakage of ascites from the stoma, are more
      frequent in patients in chronic ascites who underwent TA gastrostomy tube
      placement compared to those who underwent TO placement.

PMID- 30220590
TI  - [Examining hypertension in children and adolescents: Clinical implications of the
      differences between the European and American Guidelines].
AB  - Over the past 2 years, new guidelines for hypertension in children and adults
      have been published. The first, developed by the European Hypertension Society
      Working Group on Hypertension in Children and Adolescents, recognised the need
      for an update of the of the 2009 European Guidelines of in order to incorporate
      the new information acquired over the last few years. Subsequently, an update of
      the American guidelines (the most recent of which was in 2004), has been
      published. In both guidelines there are aspects which are agreed on, and in
      others, there are marked differences in the basic elements that have an influence
      on daily clinical practice. The main differences are centred on the criteria for
      the diagnosis and classification of hypertension, with the subsequent impact on
      its prevalence. Future studies should offer responses to all the questions that
      still remain unresolved.

PMID- 30220591
TI  - [Isolated skin lesions in a neonate: A case of congenital Langerhans cell
      histiocytosis].

PMID- 30220592
TI  - [Majocchi granuloma].

PMID- 30220593
TI  - [Prevalence of malnutrition in Spanish schoolchildren].

PMID- 30220594
TI  - "Flow-void" sign in osseous metastatic renal cell carcinoma.
AB  - AIM: To evaluate the frequency of the "flow-void" sign in a large series of
      pathologically proven renal cell carcinoma (RCC) bone metastases referred to a
      specialist unit and to evaluate its correlation with both lesion size and imaging
      sequence. A further aim was to describe a proposed grading system for the
      description of the "flow-void" sign. MATERIALS AND METHODS: A retrospective
      review of patients with magnetic resonance imaging (MRI) of pathologically proven
      RCC bone metastases between September 2007 and December 2017 was performed. MRI
      images were reviewed for the presence of the "flow-void" sign and a proposed
      grading system for this sign was applied. Statistical analysis was performed to
      determine the association between the presence of the "flow-void" sign and lesion
      size and MRI sequence. RESULTS: One hundred and forty bone lesions in 123
      patients with histologically proven metastatic RCC were reviewed. One hundred and
      thirty-two (94.3%) lesions demonstrated the "flow-void" sign on at least one
      sequence in each study. A statistically significant difference was demonstrated
      between lesion size and the presence and type of "flow-void" sign. Lesions
      demonstrating type 3 "flow-void" sign had mean dimensions of 82.2 mm compared to
      47.3 mm for lesions that did not demonstrate the "flow-void" sign (chi2(2) =11.4;
      p=0.01). T2-weighted, proton density and fat-saturated imaging also demonstrated
      the "flow-void" sign more frequently. CONCLUSION: The "flow-void" sign is a
      common imaging feature within RCC bone metastases. When observed, the "flow-void"
      sign can be a useful imaging feature in the diagnosis of RCC bone metastases.

PMID- 30220589
TI  - The center of the emotional universe: Alcohol, stress, and CRF1 amygdala
      circuitry.
AB  - The commonalities between different phases of stress and alcohol use as well as
      the high comorbidity between alcohol use disorders (AUDs) and anxiety disorders
      suggest common underlying cellular mechanisms governing the rewarding and
      aversive aspects of these related conditions. As an integrative center that
      assigns emotional salience to a wide variety of internal and external stimuli,
      the amygdala complex plays a major role in how alcohol and stress influence
      cellular physiology to produce disordered behavior. Previous work has illustrated
      the broad role of the amygdala in alcohol, stress, and anxiety. However, the
      challenge of current and future studies is to identify the specific
      dysregulations that occur within distinct amygdala circuits and subpopulations
      and the commonalities between these alterations in each disorder, with the long
      term goal of identifying potential targets for therapeutic intervention. Specific
      intra-amygdala circuits and cell type-specific subpopulations are emerging as
      critical targets for stress- and alcohol-induced plasticity, chief among them the
      corticotropin releasing factor (CRF) and CRF receptor 1 (CRF1) system. CRF and
      CRF1 have been implicated in the effects of alcohol in several amygdala nuclei,
      including the basolateral (BLA) and central amygdala (CeA); however, the precise
      circuitry involved in these effects and the role of these circuits in stress and
      anxiety are only beginning to be understood.

PMID- 30220595
TI  - Assessment of automated cone-beam CT vessel identification software during
      transarterial hepatic embolisation: radiation dose, contrast medium volume,
      processing time, and operator perspectives compared to digital subtraction
      angiography.
AB  - AIM: To evaluate arterial cone-beam computed tomography (A-CBCT) automated
      analysis software for identification of vessels supplying tumours during
      transarterial hepatic embolisation (TAE). MATERIALS AND METHODS: This study was
      approved by the institutional review board, with waiver of consent. Consecutive
      TAE procedures using arterial mapping software (AMS), and performed between
      February 2014 and August 2014, were reviewed. Hepatic arteries were imaged using
      digital subtraction angiography (DSA) as well as A-CBCT processed with AMS.
      Interventional radiologists reported1 potential embolisation target vessels
      computed using AMS versus DSA alone,2 modification of the embolisation plan based
      on AMS, and3 operator confidence related to technical success. Imaging set-up,
      processing time, radiation dose, and contrast media volume were recorded.
      RESULTS: Thirty of 34 consecutive procedures were evaluated retrospectively. At
      least one additional embolisation target vessel was identified using AMS in 13
      procedures (43%, 95% confidence interval [CI]: 26-61%) and embolisation plan
      modified in 11 (37%, 95% CI: 19-54%). Radiologists reported AMS increased
      operator confidence and reduced the number of DSA acquisitions in 25 (83%, 95%
      CI: 70-97%) and 15 cases (50%, 95% CI: 32-68%), respectively. The average A-CBCT
      acquisition and processing time was 4 minutes 53 seconds and 3 minutes 45
      seconds, respectively. A-CBCT contributed to 11% of the radiation dose and 18% of
      the contrast media volume. CONCLUSION: Physicians report increased tumour
      supplying vessel detection and intraprocedural confidence using AMS during TAE
      without substantial impact on radiation dose, contrast media volume, and
      procedure time.

PMID- 30220596
TI  - Trainee radiologist reports as a source of confirmation bias in radiology.
AB  - AIM: To assess and quantify the relationship between trainee reporting and
      radiology errors. MATERIALS AND METHODS: A retrospective analysis of the 100 most
      recent cases reviewed by a discrepancy forum in a tertiary neuroradiology service
      was performed. Data on the time of the scan and the presence of a trainee report
      were collected, with comparison being made between the cohort of erroneous
      reports and the overall service. RESULTS: Although out-of-hours imaging only
      constituted 18% of the overall service, 36% of erroneous reports originated from
      scans performed out-of-hours. Eighteen percent of scans were first reported by a
      trainee and then checked by a consultant, with the remaining 82% being solely
      reported by the consultant. Despite this, 52% of errors were from consultant
      checked trainee reports. CONCLUSION: Although out-of-hours imaging has long been
      associated with error, this study identifies consultant checking of trainee
      reports as another error-associated reporting context. This is likely to relate
      to confirmation bias, in which the pre-existing trainee report may result in
      inattentional blindness on the part of the checking consultant. Awareness of this
      phenomenon is important for the reduction of error in this specific and widely
      underestimated reporting context.

PMID- 30220597
TI  - Imaging-Based Screening Platform Assists Protein Engineering.
AB  - Protein engineering involves generating and screening large numbers of variants
      for desired properties. While modern DNA technology has made it easy to create
      protein diversity on the DNA level, the selection and validation of candidate
      proteins from large libraries remains a challenge. We built a screening platform
      that integrates high-quality fluorescence-based image analysis and robotic
      picking of bacterial colonies. It allows tracking each individual colony in a
      large population and collecting quantitative information on library composition
      during the protein evolution process. We demonstrate the power of the screening
      platform by optimizing a dim far-red-emitting fluorescent protein whose
      brightness increased several fold using iterative cycles of mutagenesis and
      platform-based screening. The resulting protein variant mCarmine is useful for
      imaging cells and structures within live tissue as well as for molecular tagging.
      Overall, the platform presented provides powerful, flexible, and low-cost
      instrumentation to accelerate many fluorescence-based protein optimization
      projects.

PMID- 30220598
TI  - Health insurance literacy and awareness of the Affordable Care Act in a
      vulnerable Hispanic population.
AB  - OBJECTIVE: The Patient Protection and Affordable Care Act (ACA) has allowed
      millions of Americans to obtain coverage. However, many, especially minorities,
      remain uninsured. With mounting evidence supporting the importance of health
      insurance literacy (HIL), the purpose of this cross-sectional study is to examine
      the association between HIL and ACA knowledge. METHODS: We conducted 681 in
      person interviews with participants at a community health event along the Texas
      Mexico border in 2015, after the conclusion of the ACA's second enrollment
      period. To assess HIL, we used the Health Insurance Literacy Measure, reflecting
      consumers' confidence to choose, compare, and use health insurance. We assessed
      ACA knowledge through the following question: "How much would you say you know
      about this health reform law?" Logistic regression was used to examine the
      association between HIL and ACA knowledge after controlling for several
      covariates. RESULTS: Almost 70% of participants knew nothing/very little about
      the ACA. Multivariate analyses revealed that no/very little ACA knowledge was
      associated with low levels of confidence "choosing health insurance plans"
      (OR:0.55; 95%CI:0.40-0.75) (full sample) and "comparing plans" (OR:0.56;
      95%CI:0.32-0.96) (U.S.-born sub-sample). CONCLUSION: No/little ACA knowledge is
      associated with lower levels of HIL. PRACTICE IMPLICATIONS: Promoting HIL is an
      essential step towards improving healthcare access.

PMID- 30220599
TI  - Stakeholder views regarding a planned primary care office-based interactive
      multimedia suicide prevention tool.
AB  - OBJECTIVES: Nearly half of all men who die by suicide visit a primary care
      clinician (PCC) in the month before death, yet few disclose suicide thoughts. We
      solicited stakeholders' views to guide development of a tailored multimedia
      program to activate middle-aged men experiencing suicide thoughts to engage with
      PCCs. METHODS: We conducted semi-structured interviews with 44 adults self
      identifying as: suicide attempt survivor; family member/loved one of person(s)
      who attempted or died by suicide; PCC; non-PCC office staff; health
      administrator; and/or prevention advocate. We coded recorded interview
      transcripts and identified relevant themes using grounded theory. RESULTS: Two
      thematic groupings emerged, informing program design: structure and delivery
      (including belief the program could be effective and desire for use of plain
      language and media over text); and informational and motivational content
      (including concerns about PCC preparedness; fear that disclosing suicide thoughts
      would necessitate hospitalization; and influence of male identity and
      masculinity, respectively, in care-seeking for and interpreting suicide
      thoughts). CONCLUSION: Stakeholder input informed the design of a primary care
      tailored multimedia suicide prevention tool. PRACTICE IMPLICATIONS: In revealing
      a previously unreported barrier to disclosing suicide thoughts to PCCs (fear of
      hospitalization), and underscoring known barriers, the findings may suggest
      additional suicide prevention approaches.

PMID- 30220601
TI  - Supporting breastfeeding for infants born to opioid dependent mothers June 18,
      2018.

PMID- 30220602
TI  - Discovery of DS-6930, a potent selective PPARgamma modulator. Part II: Lead
      optimization.
AB  - Attempts were made to reduce the lipophilicity of previously synthesized compound
      (II) for the avoidance of hepatotoxicity. The replacement of the left-hand side
      benzene with 2-pyridine resulted in the substantial loss of potency. Because poor
      membrane permeability was responsible for poor potency in vitro, the adjustment
      of lipophilicity was examined, which resulted in the discovery of dimethyl
      pyridine derivative (I, DS-6930). In preclinical studies, DS-6930 demonstrated
      high PPARgamma agonist potency with robust plasma glucose reduction. DS-6930
      maintained diminished PPARgamma-related adverse effects upon toxicological
      evaluation in vivo, and demonstrated no hepatotoxicity. Cofactor recruitment
      assay showed that several cofactors, such as RIP140 and PGC1, were significantly
      recruited, whereas several canonical factors was not affected. This selective
      cofactor recruitment was caused due to the distinct binding mode of DS-6930. The
      calcium salt, DS-6930b, which is expected to be an effective inducer of insulin
      sensitization without edema, could be evaluated clinically in T2DM patients.

PMID- 30220603
TI  - Everolimus plus endocrine vs endocrine therapy in treatment advanced ER+, HER2-
      breast cancer patients: A meta-analysis.
AB  - The purpose of this review was to compare the efficacy and safety of everolimus
      plus endocrine therapy with endocrine therapy for hormone receptor-positive,
      human epidermal growth factor 2 negative advanced breast cancer patients. We
      comprehensively searched the PubMed, the Cochrane Library, EMBASE, Web of
      Science, Chinese biomedicine literature database, WanFang Data, CNKI, and VIP
      database for relevant articles. The retrieval time limit is from building the
      database to July 2018. The computer search was supplemented with a manual search
      of reference lists for all available review articles. We scanned references of
      all included studies for additional studies. We included 7 randomized trials
      involving 1527 patients. Meta-analysis results are as follows: Everolimus plus
      endocrine therapy group is significantly better than endocrine therapy group in
      progression-free survival and clinical benefit rate, (hazard ratio [HR] = 0.48,
      95% confidence interval [CI 0.42-0.55], P < 0.00001) and (risk ratio = 1.9, 95%
      CI [1.60-2.26], P < 0.00001). But there was no significant difference between the
      2 groups in overall response rate and time to definitive deterioration (risk
      ratio = 4.37, 95% CI [0.79-24.27], P = 0.21) and (HR = 0.74, 95% CI [0.49-1.11],
      P = 0.15). In terms of safety, the incidence rate in everolimus plus endocrine
      therapy was higher than that in endocrine therapy group. Most frequently reported
      adverse events associated with everolimus treatment were stomatitis, rash,
      fatigue, diarrhea, decreased appetite, cough, dyspnea, and pneumonitis. The
      incidences of grade 3-4 adverse events were stomatitis, fatigue, diarrhea,
      pneumonitis, and hyperglycemia. Everolimus increased the efficacy of endocrine
      therapy in treatment advanced endocrine receptor-positive, human epidermal growth
      factor 2 negative breast cancer patients, and the safety profile of the
      combination is acceptable.

PMID- 30220600
TI  - Preserving replication fork integrity and competence via the homologous
      recombination pathway.
AB  - Flaws in the DNA replication process have emerged as a leading driver of genome
      instability in human diseases. Alteration to replication fork progression is a
      defining feature of replication stress and the consequent failure to maintain
      fork integrity and complete genome duplication within a single round of S-phase
      compromises genetic integrity. This includes increased mutation rates, small and
      large scale genomic rearrangement and deleterious consequences for the subsequent
      mitosis that result in the transmission of additional DNA damage to the daughter
      cells. Therefore, preserving fork integrity and replication competence is an
      important aspect of how cells respond to replication stress and avoid genetic
      change. Homologous recombination is a pivotal pathway in the maintenance of
      genome integrity in the face of replication stress. Here we review our recent
      understanding of the mechanisms by which homologous recombination acts to
      protect, restart and repair replication forks. We discuss the dynamics of these
      genetically distinct functions and their contribution to faithful
      mitoticsegregation.

PMID- 30220604
TI  - More dismal prognosis for breast cancer brain metastases? Real-world evidence
      from a SEER-based study.

PMID- 30220605
TI  - Central activation of cardiac vagal nerve by alpha2-adrenergic stimulation is
      impaired in streptozotocin-induced type 1 diabetic rats.
AB  - To elucidate the abnormality of cardiac vagal control in streptozotocin-induced
      type 1 diabetic rats, we measured left ventricular myocardial interstitial
      acetylcholine (ACh) release in response to alpha2-adrenergic stimulation as an
      index of in vivo cardiac vagal nerve activity. A cardiac microdialysis technique
      was applied to the rat left ventricle, and the effect of alpha2-adrenergic
      stimulation by intravenous medetomidine (100 MUg/kg) on myocardial interstitial
      ACh levels was examined in anesthetized diabetic rats (4-6 weeks after
      intraperitoneal streptozotocin) and age-matched control rats (protocol 1). The
      effect of electrical vagal nerve stimulation on ACh levels was also examined in
      separate rats (protocol 2). In protocol 1, medetomidine increased the ACh levels
      in control (from 1.76 +/- 0.65 to 3.13 +/- 1.41 nM, P < 0.05, n = 7) but not in
      diabetic rats (from 2.01 +/- 0.47 to 1.62 +/- 0.34 nM, not significant, n = 7).
      In protocol 2, electrical vagal nerve stimulation at 20 Hz significantly
      increased the ACh levels in both control (from 1.49 +/- 0.26 to 6.39 +/- 1.81 nM,
      P < 0.001, n = 6) and diabetic rats (from 1.77 +/- 0.54 to 6.98 +/- 1.38 nM, P <
      0.001, n = 6). In conclusion, medetomidine-induced central vagal activation was
      impaired in diabetic rats, whereas peripheral cardiac vagal control of ACh
      release was preserved. The impairment of central vagal activation may lead to
      relative sympathetic predominance and promote cardiovascular complications in
      diabetes.

PMID- 30220606
TI  - Sperm quality characteristics and fertilization capacity after cryopreservation
      of rooster semen in extender exposed to a magnetic field.
AB  - There has not been as much success in the effectiveness of avian semen
      cryopreservation as that of mammalian semen cryopreservation. This has been
      attributed to the unique characteristics of poultry sperm. In the area of
      mammalian semen, the use of magnetized extenders has enhanced the cryo-resistance
      of sperm in some species. The applicability of this strategy to avian semen has
      not yet been evaluated. The purpose of this study was to evaluate the effects on
      sperm quality and fertility after magnetization of extenders and use of these
      extenders for cryopreservation of rooster semen. Extenders were passed between
      two neodymium magnets that produced different magnetic induction values (0, 2000,
      4000 and 6000 G). Physicochemical properties of the extenders were assessed and
      then semen samples were cryopreserved in the magnetized extenders. The smallest
      cluster sizes and zeta potentials in the extenders were observed in the extender
      magnetized at 2000 gauss (G). There were greater percentages of sperm total
      motility, viability and mitochondrial membrane potential in semen treated with
      the extender magnetized at 2000 G A greater percentage of sperm with enhanced
      membrane functionality was observed when sperm were stored in extenders
      magnetized with 2000 G and 4000 G. In a field trial, there were greater
      percentages of fertility and hatching rates of eggs using semen treated with
      extenders magnetized at 2000 G and 4000 G. Cryopreservation of rooster semen with
      magnetized extenders at 2000-4000 G resulted in enhanced quality indices of
      thawed sperm as well as the fertility capacity of the cryopreserved semen.

PMID- 30220607
TI  - Unexpected AChE inhibitory activity of (2E)alpha,beta-unsaturated fatty acids.
AB  - A small library of (E) alpha,beta-unsaturated fatty acids was prepared, and 20
      different saturated and mono-unsaturated fatty acids differing in chain length
      were subjected to Ellman's assays to determine their ability to act as inhibitors
      for AChE or BChE. While the compounds were only very weak inhibitors of BChE,
      seven molecules were inhibitors of AChE holding IC50 = 4.3-12.8 M with three of
      them as significant inhibitors of this enzyme. The results have shown trans 2
      mono-unsaturated fatty acids are better inhibitors for AChE than their saturated
      analogs. Furthermore, the screening results indicate that the chain length is
      crucial for obtaining an inhibitory efficacy. The best results were obtained for
      (2E) eicosenoic acid (14) showing inhibition constants Ki = 1.51 +/- 0.09 M and
      Ki' = 7.15 +/- 0.55 M. All tested compounds were mixed-type inhibitors with a
      dominating competitive part. Molecular modelling calculations indicate a
      different binding mode of active/inactive compounds for the enzymes AChE and
      BChE.

PMID- 30220608
TI  - The impact and effect of emotional resilience on performance: an overview for
      surgeons and other healthcare professionals.
AB  - Medicine and surgery can be demanding professions with high levels of burnout,
      but few healthcare professionals are given training or education in the
      management of stress, and the ability of individuals to cope with work and other
      pressures is often taken for granted. Emotional resilience - the ability to
      recover from a stressful event, whether at work or at home - is influenced by
      factors that are both within and outside our control. In this review, we provide
      an overview of emotional resilience for surgeons and other healthcare
      professionals, and focus on the factors that can be modulated to help us cope
      with difficult or complex situations. We also discuss the importance of teamwork
      and camaraderie, which can easily be forgotten in busy working practice. A
      greater awareness and understanding of emotional resilience and ways to cope with
      stress and pressure at work are essential if we are to look after ourselves
      better, improve the work of our teams, and provide the best care for our
      patients.

PMID- 30220609
TI  - Manufacture of a high definition ocular prosthesis.

PMID- 30220610
TI  - Neurosensory recovery after trauma to the orbital floor: a prospective trial with
      dexamethasone.
AB  - Our aims were to document the occurrence of neurosensory disturbances of the
      infraorbital nerve six months after operation for an orbital blow-out fracture,
      and to find out whether dexamethasone facilitates neurosensory regeneration.
      Patients were randomly assigned to one of two groups: the study group was given a
      total of dexamethasone 30mg, whereas the control group were given neither
      glucocorticoid nor placebo. Each patient's infraorbital neurosensory state was
      recorded preoperatively, immediately postoperatively, and six months later. A
      total of 18 patients were included, eight of whom had neurosensory disturbances
      six months after the initial trauma that was not affected by dexamethasone. Six
      of the seven patients who had a delay of seven days or more between trauma and
      operation had significantly prolonged disturbance at the 180-day clinical follow
      up compared with those in whom it was less than seven days (p=0.005). Other
      possible predictors made no significant difference. Although dexamethasone did
      not facilitate sensory recovery, its benefits in the management of pain and
      reduction of swelling may justify its use in the management of facial trauma in
      selected patients.

PMID- 30220611
TI  - Primary reconstruction of orbital fractures using patient-specific titanium
      milled implants: the Helsinki protocol.
AB  - Preoperative virtual planning and the use of patient-specific implants enable
      exact reconstruction of orbital fractures. We present our results and experience
      of reconstruction of isolated orbital fractures with patient-specific implants,
      according to the Helsinki protocol, in 15 patients who were followed up for at
      least three months postoperatively. The mean (range) difference between the
      positions of virtually planned, and postoperative, implants was 1.9 (0.5-5.6) mm.
      The postoperative volume of the fractured orbit was 1.34ml less than that of the
      non-fractured side, but this was not clinically relevant. None of the patients
      required reoperation and none had any implant-related complications during follow
      up. We conclude that patient-specific implants are an adaptable and reliable
      treatment for primary orbital trauma, and that the Helsinki protocol may have
      wider applications in the treatment of facial fractures.

PMID- 30220612
TI  - Margins and survival in oral cancer.
AB  - In the surgical management of oral squamous cell carcinoma (SCC) we aim to resect
      the tumour with clear margins in all planes. The aim of this study was to
      identify and compare overall survival in a group of 591 patients who had
      resections, and to relate this to the clearance of margins at the tumour bed. We
      used life tables to calculate survival at one, two, three, five, and 10 years
      after diagnosis by margin (clear=5mm or more; close=2-5mm; and involved=less than
      2mm). Kaplan-Meier curves were produced for the margins alone, which were defined
      as clear in 480 patients (81%), close in 63 (11%), and involved in 48 (8%). Five
      year survival was 81%, 75%, and 54% for clear, close, and involved margins,
      respectively, which highlights the importance of clear margins for survival.
      There is a significant prognostic implication associated with close, and
      particularly with involved, margins.

PMID- 30220613
TI  - Elective Management of the Neck in Parotid Tumours.
AB  - AIMS: Management of the clinically node-negative (cN0) neck for parotid tumours
      remains controversial. Options include observation, elective neck dissection
      (END) or elective nodal irradiation (ENI). We reviewed the evidence for ENI on a
      background of current practice among UK clinical oncologists. MATERIALS AND
      METHODS: We carried out a systematic search of PubMed between 1 January 1980 and
      31 December 2016. Articles on patients treated with parotidectomy and either END
      or ENI, and studies on nodal patterns of disease, were included. UK clinical
      oncologists were asked to complete an online questionnaire regarding their use of
      neck radiotherapy in this setting. RESULTS: From 96 references, 20 studies met
      the inclusion criteria: 11 reported on END, five on ENI and two on both. Eight
      studies reported on nodal patterns of disease. The prevalence of occult nodal
      metastases after END ranged from 0 to 45%. Five year locoregional control was
      variable (range 64-100%). For ENI, 5 year locoregional control varied from 74 to
      100%. High-grade and T3/T4 tumours were factors for nodal relapse after END or
      ENI, which most commonly occurred in levels I-III. For the survey, 33/50 (66%) of
      cancer centres responded. Fourteen (42%) centres had guidelines for ENI. Most
      centres considered high-grade tumours (96%), T3/T4 disease (80%) and
      lymphovascular invasion (88%) as indications for ENI. Twelve centres (36%)
      irradiated levels Ib-IV electively; the remaining centres treated other various
      combinations of nodal levels. CONCLUSION: There is heterogeneity in the use and
      indications for ENI in the UK. ENI is a reasonable alternative to END as elective
      management for the cN0 neck in patients with high-grade tumours or T3/T4 disease.
      The elective clinical target volume should at least encompass nodal levels I-III.

PMID- 30220614
TI  - Sorting Out the Best: Enriching Hematopoietic Stem Cells for Gene Therapy and
      Editing.

PMID- 30220615
TI  - Retrospective investigation of 9 years of data on needlestick and sharps
      injuries: Effect of a hospital infection control committee.
AB  - BACKGROUND: The risk of occupational transmission of bloodborne pathogens to
      health care workers is primarily associated with needlestick and sharps injuries
      (NSIs). However, most NSIs are not reported, and most health care workers are not
      aware of postexposure procedures. METHODS: Data for NSIs reported in our hospital
      between 2008 and 2016 were reviewed retrospectively. RESULTS: A total of 546
      staff members reported NSIs. Of these, 376 (68.9%) were women. NSIs were more
      commonly reported by trainee nurses (243 [44.5%]), followed by nurses (121
      [22.2%]), cleaning staff (108 [19.8%]), and doctors (49 [9%]). The rate of
      postexposure interventions was 13% in 2008 and 92.6% in 2016 (P < .0001; chi2 =
      82.866). NSI rates also show that the number of applications with NSIs increased
      over the years. When occupational blood exposure was examined, the number of
      bloodborne pathogens was 50 (9.3%) cases of hepatitis B virus, 30 (5.6%) cases of
      hepatitis C virus, 3 cases of Crimean-Congo hemorrhagic fever, 1 case of HIV, and
      2 cases of hepatitis B virus and hepatitis C virus coinfection. DISCUSSION: Over
      the years, the increase in both the appropriate intervention rate and the number
      of reports to the hospital infection control committee after NSIs shows that
      regular training regarding NSIs is effective. CONCLUSIONS: Hospital infection
      control committees may play a more active role in raising awareness in this
      regard and thus reducing the rate of unreported NSIs.

PMID- 30220616
TI  - High-risk medication use for Clostridium difficile infection among hospitalized
      patients with cancer.
AB  - Patients with cancer are vulnerable to Clostridium difficile infection (CDI);
      hospitals with larger oncology populations may have worse CDI performance. Among
      71 academic hospitals studied, there were significant differences in oncology
      patient-days per 1,000 admissions across CDI standardized infection ratio
      categories of better, no different, and worse; worse hospitals had the greatest
      number of patient-days. Oncology patients' most commonly used high-risk CDI
      medications were quinolones, third- and fourth-generation cephalosporins, and
      proton pump inhibitors.

PMID- 30220617
TI  - Carbapenemase-producing Enterobacteriaceae among pregnant women and newborns in
      Algeria: Prevalence, molecular characterization, maternal-neonatal transmission,
      and risk factors for carriage.
AB  - The diffusion of carbapenemase-producing Enterobacteriaceae (CPE) represents a
      worldwide public health problem. This study revealed that the prevalence of OXA
      48-producing enterobacteria was 4.6% (19/414) and 1.6% (7/422) in mothers and
      newborns, respectively, from 2 maternity units in Algeria. Previous hospital
      admission was an independent factor associated with an increased risk of CPE
      carriage in the mothers (P = .021). The low birth weight was significantly
      associated with this carriage in the newborns (P = .008). The screening of these
      bacteria is essential to prevent the dissemination of CPE.

PMID- 30220618
TI  - Arthroscopic scapholunate dorsal capsulodesis: A 30-patient case series comparing
      postoperative splint immobilization versus immobilization and connected K-wiring.
AB  - The aim of this retrospective study was to compare the results of arthroscopic
      dorsal capsulodesis performed with or without temporary K-wiring to treat
      patients who had sustained scapholunate ligament injuries. Our case series
      included 30 patients with an average age of 37 years (range: 19-55) of whom 12
      were female. Dorsal scapholunate capsulodesis was carried out in all patients. In
      15 patients, splint immobilization only was used (group I). For the remaining 15
      patients, supplementary scapholunate and scaphocapitate K-wiring was performed
      (group II). The outcomes, whether K-wiring was used or not, were not as good as
      the outcomes of other published studies. In our study, the reported QuickDASH
      score was on average higher than 20/100, pain score was higher than 2/10, grip
      strength was less than 70% of the contralateral side. There was one postoperative
      complication in the first group and three complications in the second group; five
      cases of DISI were reported in the first group and three in the second group.
      There were no significant differences between the two groups. Based on our
      findings, supplementary K-wiring is not necessary when a dorsal scapholunate
      capsulodesis is performed. The outcomes of our study were not as good as those of
      other published series, potentially due to a shorter follow-up and the more
      severe ligament injuries in our case series.

PMID- 30220619
TI  - Drug interactions with carbamazepine: An ever expanding list?
AB  - In a study that applied a nonlinear mixed effect model to evaluate factors
      affecting steady-state serum carbamazepine concentrations in elderly nursing home
      residents, co-administration of iron supplements was reported to reduce serum
      carbamazepine concentrations by approximately one third. Although these findings
      suggest that iron ions reduce the oral bioavailability of carbamazepine, the
      influence of confounders cannot be excluded. Further studies are required to
      confirm this interaction.

PMID- 30220620
TI  - Development of three-dimensional facial expression models using morphing methods
      for fabricating facial prostheses.
AB  - PURPOSE: It is essential to fabricate a best-fit three-dimensional (3D) facial
      prosthesis model capable of facial expressions. In order for the facial
      prosthesis to remain in position, especially around marginal areas subject to
      movement, a new method of making 3D facial expression models using time-series
      data allowing changes in facial expression by morphing technique was developed.
      METHODS: Seven normal subjects and seven patients with nasal defects or nasal
      deformities participated in this study. Three distinct facial expressions (i.e.,
      a neutral expression, smiled, and open mouthed) were digitally acquired with a
      facial scanner. Prepared template models were transformed to homologous models,
      which can represent the form as shape data with the same number of point cloud
      data of the same topology referring to the scanning data. Finally, 3D facial
      expression models were completed by generating a morphing image based on two sets
      of homologous models, and the accuracy of the homologous models of all subjects
      was evaluated. RESULTS: 3D facial expression models of both normal subjects and
      patients with nasal defects were successfully generated. No significant
      differences in shape between the scanned models and homologous models were shown.
      CONCLUSIONS: The high accuracy of this 3D facial expression model in both normal
      subjects and patients suggests its use for fabricating facial prostheses.

PMID- 30220621
TI  - Effect of laser groove treatment on shear bond strength of resin-based luting
      agent to polyetheretherketone (PEEK).
AB  - PURPOSE: The mechanical properties of polyetheretherketone (PEEK) are ideally
      suited for fixed dental prostheses. However, PEEK typically has low adhesion
      strength to resin-based luting agent. This study assessed the shear bond strength
      between laser groove treated PEEK and resin-based luting agent. METHODS: A total
      of 230 specimens were randomly divided into five groups (n=46): no-treatment, air
      abrasion treatment, 100MUm-deep, 150MUm-deep, and 200MUm-deep laser groove
      treatments. The surface roughness was measured, scanning electron microscopy was
      used to observe the specimen surfaces, and X-ray photoelectron spectroscopy (XPS)
      was used to analyze the surfaces. Each group was divided into four resin-based
      luting agent subgroups: Panavia V5, RelyX Ultimate Resin Cement, G-CEM Link
      Force, and Super-Bond C&B. After the resin-based luting agent was bonded to the
      specimens, the bond strength was measured using shear tests and the failure modes
      were assessed by stereomicroscopy. The surfaces were also observed by scanning
      electron microscopy (SEM) after the shear bond strength measurements. The data
      were statistically analyzed using a two-way analysis of variance and Tukey's
      honest significant difference test (alpha=0.05). RESULTS: The PEEK surface after
      laser groove treatment groups exhibited the highest mean Ra values. In the XPS
      analysis, the laser treated PEEK surface exhibited an effective surface
      composition for bonding with resin-based luting agent. The shear bond strengths
      for the laser groove treated samples were significantly higher (p<0.05) than
      those of the no-treatment and air abrasion treatment groups. CONCLUSIONS: The
      shear bond strength between PEEK and resin-based luting agent was substantially
      improved by laser groove treatment.

PMID- 30220623
TI  - Shortfall of consultant clinical radiologists in the UK.

PMID- 30220622
TI  - Determinants of ovarian function after response-adapted therapy in patients with
      advanced Hodgkin's lymphoma (RATHL): a secondary analysis of a randomised phase 3
      trial.
AB  - BACKGROUND: Adverse effects on reproductive function are a key concern in young
      women treated with chemotherapy for advanced Hodgkin's lymphoma. We aimed to
      identify risk factors for the extent of ovarian damage in women with Hodgkin's
      lymphoma treated with different chemotherapy regimens to inform accurate advice
      on options for fertility preservation. METHODS: We recruited female participants
      from the randomised phase 3 RATHL trial, aged 18-45 years, based on availability
      of participants at recruiting sites in the UK. The RATHL trial key inclusion
      criteria were histologically confirmed classic Hodgkin's lymphoma, stage IIB-IV
      or IIA with adverse features (bulky disease or more than two sites of
      involvement), no previous treatments, and a performance status of 0-3. As part of
      RATHL, participants were treated with two cycles of doxorubicin, bleomycin,
      vinblastine, and dacarbazine (ABVD) or AVD followed by an interim PET-CT scan.
      Participants who had negative interim scans (PET score of 1 to 3 according to the
      Lugano classification) were randomly assigned (1:1) by use of minimisation,
      stratified by interim PET score and study centre, to continue ABVD or AVD for
      four more cycles. Participants with positive scans (PET score of 4 or 5) were
      escalated to treatment with bleomycin, etoposide, doxorubicin, cyclophosphamide,
      vincristine, procarbazine, and prednisolone (BEACOPP-14 or escalated BEACOPP) for
      four cycles. For the protocol-driven prospective cohort substudy, ovarian
      function was assessed before treatment, during chemotherapy, and then annually
      for 3 years by use of serum antimullerian hormone and follicle-stimulating
      hormone measurements. The RATHL study is registered with ClinicalTrials.gov,
      number NCT00678327. FINDINGS: Between Dec 13, 2010, and Dec 19, 2012, 67 eligible
      participants were recruited for this prospective cohort study; 57 had received
      ABVD or AVD (ABVD-AVD group) and ten BEACOPP-14 or escalated BEACOPP (BEACOPP
      group). Follow-up was fixed at 3 years. Antimullerian hormone concentrations
      decreased during both chemotherapy regimens. At 1 year after chemotherapy,
      antimullerian hormone concentrations recovered to a median of 10.5 pmol/L (IQR
      4.3-17.3) in the ABVD-AVD group, but little recovery was seen after BEACOPP
      (median 0.11 pmol/L [0.07-0.20]). Age also affected the extent of ovarian
      function recovery, with antimullerian hormone recovery in participants aged 35
      years or older in the ABVD-AVD group to 37% (SD 10) of their before treatment
      concentrations, compared with full recovery to 127% (SD 12) in those younger than
      35 years (p<0.0001). Follicle-stimulating hormone recovery to less than 25 IU/L
      occurred for 95% of women younger than 35 years in the ABVD-AVD group by 2 years
      and was also dependent on age (hazard ratio 0.49, 95% CI 0.37-0.65; p<0.0001).
      INTERPRETATION: Reduced recovery of ovarian function observed in women older than
      35 years treated with ABVD or AVD compared with younger women indicates that
      treatment could reduce their reproductive lifespan and supports discussion of
      fertility preservation before treatment. Women treated with BEACOPP should be
      informed of its potential high gonadotoxicity. These findings warrant further
      investigation in large, prospective studies with fertility and reproductive
      lifespan as outcomes. FUNDING: Medical Research Foundation and Cancer Research
      UK.

PMID- 30220624
TI  - Another step towards improving oncofertility counselling of young women with
      Hodgkin's lymphoma.

PMID- 30220625
TI  - Multimodality respiratory physiotherapy reduces mortality but may not prevent
      ventilator-associated pneumonia or reduce length of stay in the intensive care
      unit: a systematic review.
AB  - QUESTION: In intubated adult patients receiving mechanical ventilation, does
      multimodality respiratory physiotherapy prevent ventilator-associated pneumonia,
      shorten length of intensive care unit (ICU) stay, and reduce mortality? DESIGN: A
      systematic review with meta-analysis of randomised controlled trials.
      PARTICIPANTS: Intubated adult patients undergoing mechanical ventilation who were
      admitted to an intensive care unit. INTERVENTION: More than two respiratory
      physiotherapy techniques such as positioning or postural drainage, manual
      hyperinflation, vibration, rib springing, and suctioning. OUTCOMES MEASURES:
      Incidence of ventilator-associated pneumonia (VAP), duration of ICU stay, and
      mortality. RESULTS: Five trials were included in the meta-analysis. Random
      effects models were used to calculate pooled weighted mean difference (WMD) for
      length of ICU stay and pooled risk ratio (RR) for incidence of VAP, and fixed
      effects model was used to calculate pooled RR for mortality. The effect on the
      incidence of VAP was unclear (RR 0.73 in favour of multimodality respiratory
      physiotherapy, 95% CI 0.38 to 1.07). The effect on length of stay was also
      unclear (WMD -0.33days shorter with multimodality respiratory physiotherapy, 95%
      CI -2.31 to 1.66). However, multimodality respiratory physiotherapy significantly
      reduced mortality (RR 0.75, 95% CI 0.58 to 0.92). CONCLUSION: Multimodality
      respiratory physiotherapy appeared to reduce mortality in ICU patients. It was
      unclear whether this occurred via a reduction in the incidence of VAP and/or
      length of stay because the available data provided very imprecise estimates of
      the effect of multimodality respiratory physiotherapy on these outcomes. These
      very imprecise estimates include the possibility of very worthwhile effects on
      VAP incidence and length of ICU stay; therefore, these outcomes should be the
      focus of further investigation in rigorous trials. REGISTRATION: PROSPERO
      CRD42018094202. [Pozuelo-Carrascosa DP, Torres-Costoso A, Alvarez-Bueno C, Cavero
      Redondo I, Lopez Munoz P, Martinez-Vizcaino V (2018) Multimodality respiratory
      physiotherapy reduces mortality but may not prevent ventilator-associated
      pneumonia or reduce length of stay in the intensive care unit: a systematic
      review. Journal of Physiotherapy 64: 222-228].

PMID- 30220626
TI  - Staff and patients have mostly positive perceptions of physiotherapists working
      in emergency departments: a systematic review.
AB  - QUESTION: What are staff and patients' perceptions of physiotherapists working in
      the emergency department (ED)? DESIGN: Systematic review of qualitative studies.
      PARTICIPANTS: Staff working in EDs and patients presenting to the ED and managed
      by ED physiotherapists. OUTCOME MEASURES: Perceptions of ED staff and patients
      were synthesised using a three-stage thematic analysis consisting of extraction,
      grouping (codes), and abstraction of findings. RESULTS: Eight studies, which had
      sought the perceptions of 138 patients and 122 ED staff members, were included.
      Three main themes emerged: role of physiotherapists in the ED, positive
      perceptions of ED physiotherapists, and concerns about physiotherapists in the
      ED. Patients and ED staff both considered physiotherapists to be experts in
      musculoskeletal care. The role of ED physiotherapists was seen as providing
      thorough patient education, non-pharmacological pain management and activity
      resumption, especially through exercise therapy. Having broad knowledge to assess
      and treat different health conditions was seen as facilitating the work of
      physiotherapists in the ED. Patients and ED staff felt that ED physiotherapists
      had good interpersonal communication skills. ED staff expressed concerns
      regarding the additional time that physiotherapists spent with patients. Some
      patients felt that performing exercises in the ED was inappropriate and painful.
      CONCLUSIONS: ED physiotherapists were mostly well accepted by patients and ED
      staff, and their work was perceived to improve the ED. Concerns included
      restricted availability, lack of awareness of the role undertaken by
      physiotherapists in the ED, and increased treatment time in some settings.
      [Ferreira GE, Traeger AC, O'Keeffe M, Maher CG (2018) Staff and patients have
      mostly positive perceptions of physiotherapists working in emergency departments:
      a systematic review. Journal of Physiotherapy 64: 229-236].

PMID- 30220627
TI  - Herpes simplex virus type 1 reactivation following a severe purulent meningitis
      in ICU.

PMID- 30220629
TI  - Trends of Antiplatelet Therapy for the Management of Moyamoya Disease in Japan:
      Results of a Nationwide Survey.
AB  - BACKGROUND: The efficacy and safety of antiplatelet drugs in the treatment of
      moyamoya disease remain unclear. This study reports results of a nationwide
      survey conducted in 2016 on the trends of antiplatelet therapy for moyamoya
      disease in Japan. METHODS: Data were obtained through questionnaires related to
      treatment policies regarding antiplatelet drugs from each specialized stroke
      management department of 765 hospitals in Japan. Data were also compared between
      experienced facilities (defined as facilities managing more than 10 cases per
      year) and those less experienced (not more than 10 cases per year) to determine
      experts' opinion. RESULTS: Of the 389 departments in 375 hospitals that
      responded, 330 departments provided medical care for moyamoya disease. Regarding
      ischemic stroke, numerous departments considered the use of antiplatelet drugs
      "in principle" (218 departments). After surgery for ischemic moyamoya disease,
      the use of antiplatelet drugs for a certain period of time was the most popular
      opinion (74 departments). Regarding asymptomatic moyamoya disease, majority
      departments reported no use of APDs "in principle" (256 departments). The
      experienced facilities reported "no use of antiplatelet drugs" more frequently
      than those less experienced for treating asymptomatic moyamoya disease. In
      moyamoya disease, aspirin was the most commonly used antiplatelet drugs followed
      by cilostazol and clopidogrel. CONCLUSIONS: This survey revealed details of
      treatment policies, and the selection of antiplatelet drugs widely varied across
      facilities. Further prospective studies are necessary to improve the current
      unclear situation regarding the use of antiplatelet drugs for the management of
      moyamoya disease.

PMID- 30220630
TI  - Renin-angiotensin-aldosterone system in cirrhosis: There's room to try!

PMID- 30220628
TI  - Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation
      and Primes Precursors for Differentiation.
AB  - The in vivo niche and basic cellular properties of nephron progenitors are poorly
      described. Here we studied the cellular organization and function of the MAPK/ERK
      pathway in nephron progenitors. Live-imaging of ERK activity by a Forster
      resonance energy transfer biosensor revealed a dynamic activation pattern in
      progenitors, whereas differentiating precursors exhibited sustained activity.
      Genetic experiments demonstrate that MAPK/ERK activity controls the thickness,
      coherence, and integrity of the nephron progenitor niche. Molecularly, MAPK/ERK
      activity regulates niche organization and communication with extracellular matrix
      through PAX2 and ITGA8, and is needed for CITED1 expression denoting
      undifferentiated status. MAPK/ERK activation in nephron precursors propels
      differentiation by priming cells for distal and proximal fates induced by the Wnt
      and Notch pathways. Thus, our results demonstrate a mechanism through which
      MAPK/ERK activity controls both progenitor maintenance and differentiation by
      regulating a distinct set of targets, which maintain the biomechanical milieu of
      tissue-residing progenitors and prime precursors for nephrogenesis.

PMID- 30220631
TI  - Translation and validation of body image instruments: Challenges, good practice
      guidelines, and reporting recommendations for test adaptation.
AB  - Body image research has grown rapidly to include new cultural and linguistic
      populations, but this gives rise to a need for measurement instruments that are
      sensitive to local contextual variations while remaining equivalent across
      groups. Test adaptation, or the translation and validation of a source instrument
      for use in a new cultural group, is an important part of this process. Here, we
      offer an operational framework for conducting effective test adaptation. We cover
      good-practice guidelines for instrument translation and suggest effective
      strategies for achieving semantic equivalence of translated instruments. We also
      focus on measurement invariance and provide good-practice and reporting
      guidelines for conducting exploratory and confirmatory factor analyses. Finally,
      we suggest good-practice guidelines for demonstrating that scores on translated
      measures have good reliability and validity. It is our hope that the availability
      of this article will assist body image scholars seeking to conduct robust test
      adaptations of existing measurement tools.

PMID- 30220632
TI  - Arthroscopic-assisted inflatable bone tamp reduction for treatment of
      posterolateral tibial plateau fractures.
AB  - AIM: Our study aimed to assess the safety and efficacy of an innovative
      arthroscopic-assisted inflatable tamp reduction technique for the treatment of
      posterolateral tibial plateau fractures. PATIENTS AND METHODS: Twenty-six
      patients with posterolateral tibial plateau fractures were treated with
      arthroscopy through inflation reduction technique were enrolled. Arthroscopy was
      used to observe the reduction of articular surface to avoid over-reduction or de
      reduction. An arthroscopic assessment of anatomic joint reduction completed the
      procedure. Inflatable bone tamp was used to reduce the fractures and calcium
      phosphate cement was used as bone substitute to augment the repairs. RESULTS:
      Under arthroscopy, the reduction was observed to be excellent without any
      residual deformity in all the cases. Cement overflow into the soft tissues or the
      knee joint was not observed. During the follow-up period, no obvious articular
      surface subsidence (>5 mm) was observed and no evidence of posttraumatic
      osteoarthritis could be detected. Radiographs under full weight bearing revealed
      neither loss of reduction nor any valgus deviation. Three months after surgery,
      the graft was almost completely replaced by new bone. The functional evaluation
      following the Rasmussen score yielded excellent results. CONCLUSIONS: This study
      provided a novel technique for the reduction of depressed and split-depressed
      pasterolateral tibial plateau fractures. Arthroscopic-assisted inflatable bone
      tamp reduction is an effective method for the treatment of posterolateral tibial
      plateau fractures.

PMID- 30220633
TI  - A systematic literature review of criteria and models for casualty distribution
      in trauma related mass casualty incidents.
AB  - INTRODUCTION: Mass casualty incidents impose a large burden on the emergency
      medical systems, hospitals and community infrastructures. The pre-hospital and
      hospital capacities are usually bear the burden of casualties large numbers. One
      of the challenging issues in mass casualty incidents is the distribution of
      casualties among the suitable health care facilities. OBJECTIVE: To review models
      and criteria affecting the distribution of casualties during the trauma-related
      mass causality incidents. MATERIALS AND METHODS: A systematic literature search
      in the scientific databases which included: PubMed, Scopus and Web of Science was
      conducted. Relevant literature which was published before August 2017 was
      searched. Neither the publication date nor language limitations were considered
      in the literature search. All the trauma-related mass casualty incidents are
      included in this study. Two independent reviewers conducted the data extraction
      and quality assessment of the documents was considered using a checklist
      developed by the researchers. RESULTS: Literature search yielded 4540 documents
      of which 493 were duplicated and removed. After reviewing the titles and
      abstracts of the remaining documents (4047), only 73 documents were considered
      relevant. Finally, the inclusion and exclusion criteria were applied and only 30
      documents were considered for data extraction and quality assessment. The study
      found 491 criteria to be affecting the distribution of casualties following
      trauma-related mass casualty incidents. These are categorized as pre-hospital
      (triage, treatment and transport); hospital (space, staff, stuff, system /
      structure); incidents' characteristics and others. The criteria which were
      extracted from the models are termed as "model extracted" while the other labeled
      as "author suggested". CONCLUSION: To the best of our knowledge, this is the
      first systematic literature review on criteria affecting distribution of
      casualties following trauma-related mass casualty incidents based on the pre
      hospital and hospital capacities. SYSTEMATIC REVIEW REGISTRATION NUMBER: This
      review was registered in international prospective register of systematic reviews
      (PROSPERO) with registration number CRD42016049115.

PMID- 30220634
TI  - Epidemiology and incidence of tibia fractures in the Swedish Fracture Register.
AB  - INTRODUCTION: There is a lack of epidemiological studies of fractures in all
      segments of the tibia classified by orthopaedic surgeons according to the AO/OTA
      classification. Since 2011, the Swedish Fracture Register (SFR) has provided
      prospectively collected, population-based data on fractures of all types, treated
      both surgically and non-surgically. The aim of this study was to describe the
      epidemiology and incidence of fractures in all segments of the tibia in a cohort
      of consecutive tibia fractures over a period of five years at Sahlgrenska
      University Hospital, Gothenburg, Sweden. METHODS: Information on age, gender,
      date and mechanism of injury, fracture classification according to AO/OTA,
      affected side and high- or low-energy trauma was extracted from the SFR for all
      patients, aged 16 years and above, with tibia fractures treated at Sahlgrenska
      University Hospital, Gothenburg, during the five-year period 1 January 2011 to 31
      December 2015. RESULTS: 1325 patients sustained 1371 tibia fractures. There were
      712 proximal tibia fractures, 417 tibial shaft fractures and 242 distal tibia
      fractures. Patients with proximal tibia fractures had a higher mean age (54.3)
      and 58% were women, whereas patients with shaft and distal fractures had a
      slightly lower mean age (47.0 and 48.7 respectively) and a dominance of men (59%
      and 54% respectively). The overall incidence of tibia fractures was 51.7 per
      100,000 and year. The incidence of proximal, diaphyseal and distal tibia
      fractures was 26.9, 15.7 and 9.1 respectively per 100,000 and year. Among women,
      tibia fractures showed an increasing incidence with age in all segments, whereas
      men had a fairly flat incidence curve, except for tibial shaft fractures, which
      displayed a peak among young males. The incidence of tibia fractures and graphs
      for age-specific incidence for each segment of the tibia are presented.
      CONCLUSIONS: This study describes the epidemiology and incidence of fractures in
      the whole of the tibia classified by orthopaedic surgeons according to the AO/OTA
      classification.

PMID- 30220635
TI  - A comparison of fixation methods in adolescent patients with diaphyseal forearm
      fractures.
AB  - INTRODUCTION: The purpose of this study was to compare both bone diaphyseal
      forearm fractures in adolescent patients treated with plate fixation to patients
      treated with intramedullary fixation to identify differences in complications and
      outcomes. MATERIALS & METHODS: A retrospective study was performed on all
      adolescent patients with age between 10 and16 year and treated with
      intramedullary fixation or plate fixation for a diaphyseal both bone forearm
      fracture between 2005 and 2014. Demographic information and clinical data was
      collected. Radiographs were reviewed to evaluate post-operative radial bow
      magnitude and location, time to union, and residual angulation. Complications
      were graded using the modified Clavien-Dindo Classification system. RESULTS: A
      total of 102 patients met the inclusion criteria. Of these, 32 were treated with
      plate fixation and 70 with intramedullary fixation. The intramedullary nail group
      had 55% of complications classified as major. There were no major complications
      in the plate fixation group (P = 0.1). The radial bow was significantly more
      distal and smaller in magnitude in the intramedullary fixation group (P < 0.01).
      Of the patients who underwent intramedullary fixation, 76% required an open
      reduction of at least one forearm bone. There was increased time to radiographic
      union in patients treated with intramedullary fixation when compared to those
      treated with plates, 68 days versus 58 days (P = 0.03). A second operation was
      necessary for 91% of patients treated with intramedullary fixation compared to
      only 3% of patients treated with a plate (P < 0.01). CONCLUSION: Diaphyseal
      forearm fractures in adolescent patients remain challenging injuries to treat.
      Forearm bony anatomy is not completely restored with intramedullary fixation.
      Results suggested an association towards increased complication rates and
      complication severity with intramedullary fixation. LEVEL OF EVIDENCE: Level 3
      retrospective comparative study.

PMID- 30220636
TI  - Routine pelvic X-rays in asymptomatic hemodynamically stable blunt trauma
      patients: A meta-analysis.
AB  - INTRODUCTION: There is no consensus on how pelvic X-rays should be ordered
      selectively in blunt trauma patients which may save time, reduce radiation
      exposure and costs. The aim of this systematic review and meta-analysis was to
      assess the need for routine pelvic X-rays in awake, respiratory and
      hemodynamically (HD) stable blunt trauma patients without signs of pelvic
      fracture. Criteria to identify patients who could safely forgo pelvic X-ray were
      evaluated. METHODS: A literature search was performed for prospective comparative
      cohort studies. Inclusion criteria were: blunt force trauma, hemodynamically and
      respiratory stable and awake patients, physical examination (PE) for pelvic
      fractures was adequately described, and the reliability of negative PE findings
      could be evaluated. Primary outcome was the negative predictive value (NPV) of PE
      for all and for clinically relevant pelvic fractures. Additionally sensitivity,
      specificity and positive predictive value (PPV) were calculated. RESULTS: Ten
      studies were included; yielding a total of 11,423 patients. The NPV of PE for all
      pelvic fractures ranged from 0.96 to 1.00 with a median of 0.996. Combining
      studies, total NPV was 0.991. For clinically relevant fractures, the NPV of PE
      ranged from 0.996 to 1.00 with a median of 1.00. In patients with negative
      findings during PE, 0.9% had fractures, and 0.1% had clinically relevant
      fractures, none requiring surgical management. CONCLUSIONS: In awake,
      hemodynamically and respiratory stable blunt trauma patients, PE could identify
      those patients who could safely forgo pelvic X-ray. Selective ordering of pelvic
      X-ray may lead to a decrease in patient work-up time, lower radiation exposure,
      and reduce costs. A decision making flow chart is proposed..

PMID- 30220637
TI  - Corrigendum to "Surgical evaluation of lymph nodes in esophageal adenocarcinoma:
      Standardized approach or personalized medicine?" [European Journal of Surgical
      Oncology (2018) 1177-1180].

PMID- 30220638
TI  - The obesity paradox in cardiovascular disease: Deeper phenotyping to get to the
      heart of the matter.

PMID- 30220640
TI  - Efficacy and safety of erythropoietin in patients with traumatic brain injury: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of
      erythropoietin (EPO) on mortality and neurological outcomes in patients with
      traumatic brain injury (TBI). MATERIALS AND METHODS: Electronic databases of
      studies published up to January 5, 2017 were searched to retrieve relevant
      investigations comparing the outcomes of EPO-treated patients and untreated
      patients following TBI. We calculated the relative risk (RR) of mortality,
      neurologic outcomes, and deep vein thrombosis (DVT) with corresponding 95%
      confidence interval (CI) using meta-analysis. RESULTS: Six randomized controlled
      clinical trials met the eligibility criteria. In total, 1041 patients were
      included among the studies. EPO was found to significantly reduce the occurrence
      of mortality (RR 0.68 [95% CI 0.50-0.95]; P = 0.02), but did not significantly
      reduce poor functional outcome (RR 1.22 [95% CI 0.82-1.81]; P = 0.33). There were
      no significant differences in the occurrence of complications, such as DVT,
      between the treatment groups (RR -0.02 [95% CI -0.06-0.02]; P = 0.81).
      CONCLUSIONS: Results of the present meta-analysis suggest that the use of EPO may
      prevent death following TBI without causing adverse events, such as deep vein
      thrombosis. However, the role of EPO in improving neurological outcome(s) remains
      unclear. Further well-designed, randomized controlled trials using modified
      protocols and involving specific patient populations are required to clarify this
      issue, and to verify the findings.

PMID- 30220639
TI  - Extending research on language foundations and evolution: Reply to comments on
      "Rethinking foundations of language from a multidisciplinary perspective".

PMID- 30220641
TI  - Sedative dose and patient variable impacts on postintubation hypotension in
      emergency airway management.
AB  - PURPOSE: Postintubation hypotension (PIH) is an adverse event associated with
      poor outcomes in emergency department (ED) endotracheal intubation. This study
      aimed to evaluate the association between sedative dose adjustment and PIH during
      emergency airway management. We also investigated the impact of patient and
      procedural factors on the incidence of PIH. MATERIALS AND METHODS: This was a
      single-center, retrospective study that used a prospectively collected registry
      of airway management performed at the ED from April 2014 to February 2017. Adult
      patients who received emergency endotracheal intubation were included.
      Multivariable logistic regression models were used to evaluate the association of
      PIH with sedative dose, patient variables, and procedural variables. RESULTS:
      Overall, 689 patients were included, and 233 (33.8%) patients developed PIH. In
      the patients overall, multivariable logistic regression demonstrated that age >
      70 years, shock index >0.8, arterial acidosis (pH < 7.2), intubation indication,
      and use of non-depolarizing neuromuscular blocking agent were significantly
      related to PIH. In patients overall, the sedative dose was not related to PIH
      (overdose; OR: 1.09, 95%CI: 0.57-2.06), (reduction; OR: 0.93, 95%CI: 0.61-1.42),
      (none used; OR: 1.28, 95%CI: 0.64-2.53). In subgroup analysis, ketamine dose was
      not related to PIH (overdose; OR: 0.81, 95%CI: 0.27-2.38, reduction; OR: 1.41,
      95%CI: 0.78-2.54). Reduction of etomidate dose was significantly associated with
      decreased PIH (reduction; OR: 0.46, 95%CI: 0.22-0.98, overdose; OR: 1.77, 95%CI:
      0.79-3.93). CONCLUSIONS: PIH was mainly related to predisposing patient-related
      factors. Only adjustment of etomidate dose was associated with the incidence of
      PIH.

PMID- 30220642
TI  - Prognostic performance of disease severity scores in patients with septic shock
      presenting to the emergency department.
AB  - BACKGROUND: An accurate disease severity score that can quickly predict the
      prognosis of patients with sepsis in the emergency department (ED) can aid
      clinicians in distributing resources appropriately or making decisions for active
      resuscitation measures. This study aimed to compare the prognostic performance of
      quick sequential organ failure assessment (qSOFA) with that of other disease
      severity scores in patients with septic shock presenting to an ED. METHODS: We
      performed a prospective, observational, registry-based study. The discriminative
      ability of each disease severity score to predict 28-day mortality was evaluated
      in the overall cohort (which included patients who fulfilled previously defined
      criteria for septic shock), the newly defined sepsis subgroup, and the newly
      defined septic shock subgroup. RESULTS: A total of 991 patients were included.
      All disease severity scores had poor discriminative ability for 28-day mortality.
      The sequential organ failure assessment and acute physiology and chronic health
      evaluation II scores had the highest area under the receiver-operating
      characteristic curve (AUC) values, which were significantly higher than the AUC
      values of other disease severity scores in the overall cohort and the sepsis and
      septic shock subgroups. The discriminative ability of each disease severity score
      decreased as the mortality rate of each subgroup increased. CONCLUSIONS: All
      disease severity scores, including qSOFA, did not display good discrimination for
      28-day mortality in patients with serious infection and refractory hypotension or
      hypoperfusion; additionally, none of the included scoring tools in this study
      could consistently predict 28-day mortality in the newly defined sepsis and
      septic shock subgroups.

PMID- 30220643
TI  - Emergency physician empathy does not explain variation in admission rates.

PMID- 30220644
TI  - Comment on: Relationship between bariatric surgery and periodontal status: a
      systematic review and meta-analysis.

PMID- 30220645
TI  - Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) as a
      revisional surgery.
AB  - BACKGROUND: Few studies of single-anastomosis duodeno-ileal bypass with sleeve
      gastrectomy (SADI-S) as the revision surgery for laparoscopic adjustable gastric
      banding (LAGB) have been published. OBJECTIVES: To explore the efficacy and
      safety of SADI-S as the revision surgery for LAGB. SETTING: The research was
      completed by the University Hospital. METHODS: From November 2013 to November
      2015, a total of 22 weight-regain patients who previously underwent LAGB received
      SADI-S as the revision surgery at the People's Liberation Army General Hospital.
      Preoperative clinical characteristics as well as the data at 1, 3, 6, 12, 18, and
      24 months after operation were collected and analyzed. RESULTS: The operation
      time of SADI-S was 105 +/- 12.2 minutes, and intraoperative blood loss was 27.3
      +/- 5.8 mL. The percentage of excess weight loss was 20.55 +/- 9.10%, 40.1 +/-
      6.02%, 63.52 +/- 10.43%, 70.72 +/- 8.54%, 78.34 +/- 9.25%, and 81.57 +/- 11.12%
      at 1, 3, 6, 12, 18 and 24 months after surgery, respectively. The 2-year complete
      remission rate of type 2 diabetes was 17 of 18, and the partial remission rate
      was 1 of 18 after operation. The glycated hemoglobin was 8.7% +/- 1.1%, 7.7% +/-
      .9%, 6.2% +/- .6%, 5.7% +/- .5%, 5.5% +/- .6%, 6.0% +/- .9%, and 5.7% +/- .8%
      preoperatively and at 1, 3, 6, 12, 18, and 24 months after the operation,
      respectively. One case presented incisional hernia and was repaired. There was no
      conversion to laparotomy. Vitamins and trace elements were administrated long
      term to these patients after the operation, and no patients experienced vitamin
      or trace element deficiencies. CONCLUSION: SADI-S is safe and effective as a
      revision surgery for patients who experienced weight regain after LAGB. However,
      multicenter randomized controlled studies with larger sample sizes are needed to
      explore the long-term efficacy and safety of SADI-S.

PMID- 30220646
TI  - Daily aspirin doesn't prevent deaths or disability in healthy older people, trial
      finds.

PMID- 30220647
TI  - Witnessing violence in early secondary school predicts subsequent student
      impairment.
AB  - BACKGROUND: Past research suggests that adolescents who witness violence are at
      risk of adjustment problems. However, few studies have implemented a longitudinal
      design and have accounted for direct experiences of victimisation and other major
      confounders. This prospective study examines the relationship between witnessing
      school violence and subsequent impairment and whether such associations depend on
      the kind of violence witnessed. METHODS: 3936 adolescents from Quebec (Canada)
      were followed from ages 12 through 15 years. Linear regression tested
      associations between witnessing school violence at age 13 and subsequent
      antisocial behaviour (drug use, delinquency), emotional distress (social anxiety,
      depressive symptoms) and academic adjustment (school achievement, engagement) at
      age 15. We compared the relative contribution of differing forms of witnessing
      school violence versus being victimised directly. RESULTS: General school
      violence predicted later impairment. The adjusted associations between indirectly
      experiencing violence as a bystander and subsequent impairment were comparable to
      those of direct victimisation. Witnessing covert and major violence was
      associated with drug use and delinquency. Witnessing minor violence was
      associated with increases in drug use, social anxiety, depressive symptoms and
      decreases in school engagement. CONCLUSIONS: Almost all students witnessed school
      violence, which predicted impairment. Witnessing violence was associated with
      risk of subsequent adjustment problems 2 years later. Directly experienced
      victimisation showed a comparable magnitude of risk. This suggests that when it
      comes to symptoms of conduct disorder, witnessing violence might have the same
      impact as experiencing it directly. Witnessing earlier covert and major violence
      predicted social impairment whereas minor violence predicted psychological and
      academic impairment.

PMID- 30220648
TI  - Budesonide/formoterol MDI with co-suspension delivery technology in COPD: the
      TELOS study.
AB  - TELOS compared budesonide (BD)/formoterol fumarate dihydrate (FF) metered dose
      inhaler (BFF MDI), formulated using innovative co-suspension delivery technology
      that enables consistent aerosol performance, with its monocomponents and
      budesonide/formoterol fumarate dihydrate dry powder inhaler (DPI) in patients
      with moderate to very severe chronic obstructive pulmonary disease (COPD),
      without a requirement for an exacerbation history.In this phase III, double
      blind, parallel-group, 24-week study (NCT02766608), patients were randomised to
      BFF MDI 320/10 ug (n=664), BFF MDI 160/10 ug (n=649), FF MDI 10 ug (n=648), BD
      MDI 320 ug (n=209) or open-label budesonide/formoterol DPI 400/12 ug (n=219).
      Primary end-points were change from baseline in morning pre-dose trough forced
      expiratory volume in 1 s (FEV1) and FEV1 area under the curve from 0-4 h (AUC0
      4). Time to first and rate of moderate/severe exacerbations were assessed.BFF MDI
      320/10 ug improved pre-dose trough FEV1versus FF MDI (least squares mean (LSM) 39
      mL; p=0.0018), and BFF MDI 320/10 ug and 160/10 ug improved FEV1 AUC0-4versus BD
      MDI (LSM 173 mL and 157 mL, respectively; both p<0.0001) at week 24. BFF MDI
      320/10 ug and 160/10 ug improved time to first and rate of moderate/severe
      exacerbations versus FF MDI. Treatments were well tolerated, with pneumonia
      incidence ranging from 0.5-1.4%.BFF MDI improved lung function versus
      monocomponents and exacerbations versus FF MDI in patients with moderate to very
      severe COPD.

PMID- 30220649
TI  - New steps forward for obstructive sleep apnoea in the era of precision medicine.

PMID- 30220650
TI  - Pulmonary endarterectomy and the cost of patient refusal.

PMID- 30220651
TI  - The use of hydrogels for cell-based treatment of chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a major and growing public health concern with
      increasing incidence and prevalence worldwide. The therapeutic potential of stem
      cell therapy, including mesenchymal stem cells (MSCs) and endothelial progenitor
      cells (EPCs) holds great promise for treatment of CKD. However, there are
      significant bottlenecks in the clinical translation due to the reduced number of
      transplanted cells and the duration of their presence at the site of tissue
      damage. Bioengineered hydrogels may provide a route of cell delivery to enhance
      treatment efficacy and optimise the targeting effectiveness while minimising any
      loss of cell function. In this review, we highlight the advances in stem cell
      therapy targeting kidney disease and discuss the emerging role of hydrogel
      delivery systems to fully realise the potential of adult stem cells as a
      regenerative therapy for CKD in humans. MSCs and EPCs mediate kidney repair
      through distinct paracrine effects. As a delivery system, hydrogels can prolong
      these paracrine effects by improving retention at the site of injury and
      protecting the transplanted cells from the harsh inflammatory microenvironment.
      We also discuss the features of a hydrogel, which may be tuned to optimise the
      therapeutic potential of encapsulated stem cells, including cell-adhesive
      epitopes, material stiffness, nanotopography, modes of gelation and degradation
      and the inclusion of bioactive molecules. This review concludes with a discussion
      of the challenges to be met for the widespread clinical use of hydrogel delivery
      system of stem cell therapy for CKD.

PMID- 30220652
TI  - Adenylyl cyclase 6 in acid-base balance - adding complexity.
AB  - Systemic acid-base balance is tightly controlled within a narrow range of pH.
      Disturbances in systemic acid-base homeostasis are associated with diverse
      detrimental effects. The kidney is a key regulator of acid-base balance, capable
      of excreting HCO3- or H+, and chronic kidney disease invariably leads to
      acidosis. However, the regulatory pathways underlying the fine-tuned acid-base
      sensing and regulatory mechanisms are still incompletely understood. In the
      article published recently in Clinical Science (vol 132 (16) 1779-1796), Poulson
      and colleagues investigated the role of adenylyl cyclase 6 (AC6) in acid-base
      homeostasis. They uncovered a complex role of AC6, specifically affecting acid
      base balance during HCO3- load, which causes pronounced alkalosis in AC6
      deficient mice. However, the phenotype of AC6-deficient mice appears much more
      complex, involving systemic effects associated with increased energy expenditure.
      These observations remind us that there is much to be learned about the intricate
      signaling pathways involved in renal control of acid-base balance and the complex
      ramifications of acid-base regulation.

PMID- 30220654
TI  - Negative results worth publishing.

PMID- 30220653
TI  - Buffering chronic kidney disease with sodium bicarbonate.
AB  - The roles of the kidney are well defined, if there is a progressive loss in renal
      function, the kidney is no longer able to perform the listed tasks and chronic
      kidney disease (CKD) persists. In both clinical and experimental studies, NaHCO3
      supplementation has been shown to improve glomerular filtration rate (GFR) as
      well as halt the progression toward end-stage renal disease (ESRD). In an article
      recently published in Clinical Science (vol 132 (11) 1179-1197), Ray et al.
      presented an intriguing and timely study, which investigates the mechanisms
      involved in the protection that follows oral NaHCO3 ingestion. Here we comment on
      their research findings.

PMID- 30220655
TI  - Pitfalls in cytokine measurements - Plasma TGF-beta1 in chronic fatigue syndrome.
AB  - BACKGROUND: Serum TGF-beta1 concentrations are reported to be elevated in chronic
      fatigue syndrome (CFS). However, measurement of circulating cytokines is a
      complex procedure and control of pre-analytical procedures is essential. The
      objective of the current study was to measure circulating TGF-beta1
      concentrations in CFS patients compared to healthy controls, taking into account
      differences in pre-analytical procedures. METHODS: Two cohorts of female CFS
      patients were included. In both studies patients were asked to bring a healthy,
      age-matched control. At baseline, TGF-beta1 levels were measured in plasma and
      additionally P-selectin, a marker of platelet activity, was determined in a
      subgroup of participants. RESULTS: 50 patients and 48 controls were included in
      cohort I, and 90 patients and 29 controls in cohort II. Within the cohorts there
      were no differences in TGF-beta1 concentrations. However, between the cohorts
      there was a large discrepancy, which appeared to be caused by differences in g
      force of the centrifuges used. The lower g-force used in cohort II (1361 g)
      caused more platelet activation, reflected by higher p-selectin concentrations,
      compared to cohort I (p < 0.0001), which was confirmed in a second independent
      experiment. There was a correlation between TGF-beta1 and p-selectin
      concentrations (r 0.79, p < 0.0001). CONCLUSION: These results demonstrate that
      control of pre-analytical procedures is an essential aspect when measuring
      circulating cytokines. No evidence for enhanced TGF-beta1 in patients with CFS
      was found.

PMID- 30220656
TI  - Occurrence and management of an aberrant free T4 in combination with a normal
      TSH.
AB  - BACKGROUND: Thyroid function tests may show the combination of a normal
      concentration of serum thyroidstimulating hormone (TSH) and an increased or
      decreased level of free thyroxine (free T4). How often this occurs is unclear and
      not everyone is familiar with how it should be adressed. METHODS: We conducted a
      retrospective cohort study of all adult patients who presented at a non-academic
      general hospital in the Netherlands between 1 January 2010 and 31 December 2014
      and yielded an increased or decreased free T4 in combination with a normal TSH.
      Exclusion criteria included the use of thyroid medication, pregnancy, a history
      of thyroid surgery and treatment with radioactive iodine. The medical records of
      the patients included were retrieved and evaluated. RESULTS: Of the 30,143
      combined TSH and free T4 measurements in 23,199 individual patients, 1005
      measurements (3.33%) in 775 patients (3.34%) yielded an aberrant free T4 in
      combination with a normal TSH. 398 patients (1.72%) had a persistent aberrant
      free T4, 349 (87.7%) of whom had a decreased free T4 and 49 (12.3%) an increased
      free T4. In 58 of the 398 patients (14.6%) with a persistent abberant free T4 a
      possible cause was established by the treating physician. However, upon re
      examination of medical files a possible causative factor could be identified in
      123 patients (30.9%). CONCLUSION: In our study population the prevalence of
      hyperthyroxinemia or hypothyroxinemia in combination with a normal TSH was 334
      per 10.000 patients. When records were thoroughly searched, identification of
      potential causative factors increased substantially. Clinicians should be
      encouraged to check for underlying causes.

PMID- 30220657
TI  - Management of S. aureus bacteraemia in the Netherlands; infectious diseases
      consultation improves outcome.
AB  - BACKGROUND: Staphylococcus aureus bacteraemia is associated with a high mortality
      rate. Previously it has been shown that consultation by an internist-infectious
      diseases specialist (IDS) improves the outcome of patients. In this study, we
      evaluated the differences in management and outcome between patients with, and
      those without IDS consultation. METHODS: All adult patients with a positive blood
      culture for S. aureus from January 2010 to December 2013 were retrospectively
      identified with the electronic registration system of our Laboratory for Medical
      Microbiology. Clinical and microbiological characteristics were retrieved from
      the electronic patient files, as well as information on bedside consultation by
      an IDS. RESULTS: A total of 234 patients with S. aureus bacteraemia were included
      in the study, of whom 77.8% were consulted by an IDS. Management of patients with
      IDS consultation was more often according to guidelines than was the case without
      consultation by an IDS; follow up blood cultures were taken more often (97.8% vs.
      80.8%, p < 0.001), patients received echocardiography more often (70.9% vs.
      50.0%, p = 0.007), and they were more often treated adequately (86.6% vs. 59.2%,
      p < 0.001). The detection rate of complications in the IDS group was higher
      (59.3% vs. 32.7%, p = 0.001) and 30-day mortality rate was lower (12.1% vs.
      23.1%, p = 0.04). This was confirmed by multivariate analysis. CONCLUSION: In
      patients with a S. aureus bacteraemia, bedside consultation by an IDS results in
      better adherence to diagnostic and treatment guidelines, with higher detection of
      complications and a higher survival rate.

PMID- 30220658
TI  - Coronary artery spasms due to tyrosine kinase inhibitors used in chronic myeloid
      leukemia.
AB  - Tyrosine kinase inhibitors (TKIs) have changed the landscape of treatment for
      patients with chronic myeloid leukemia (CML) leading to a life expectancy
      comparable to the general population. Side effects commonly encountered during
      TKI treatment are pleural effusion due to use of dasatinib and vascular side
      effects due to nilotinib and ponatinib. Coronary artery spasm (CAS), although
      encountered during treatment with other chemotherapeutic drugs, have to our
      knowledge never been reported during TKI treatment. Here, we describe two cases
      of coronary artery spasms which are likely due to TKIs.

PMID- 30220659
TI  - Ticking off diagnoses of abdominal pain: early neuroborreliosis with
      radiculopathy.
AB  - Lyme disease (LD) is the most common tick-borne illness. The diagnosis of LD is
      difficult because of the great variation in clinical manifestations. Although
      abdominal pain is generally not considered a sign of LD, in this case report we
      describe a patient with unexplained severe abdominal pain that eventually turned
      out to be LD due to radiculopathy. Since the incidence of LD is rising it is
      important to realise that severe abdominal pain could be the first clinical
      manifestation of early neuroborreliosis.

PMID- 30220660
TI  - Subacute renal injury in hypothyroidism: a case report of an unusual phenomenon.
AB  - Severe hypothyroidism is known to cause elevation of creatinine and this
      phenomenon has been reported in clinical settings in the past. Screening for
      hypothyroidism is not regularly performed in the differential workup for acute
      kidney injury due to its rare presentation. Therefore, to most physicians
      hypothyroidism is not known as a cause of acute kidney injury. In this clinical
      case report, we describe a case of subacute kidney injury in a patient with
      severe hypothyroidism prior to iodine-131 ablation therapy. Hypothyroidism was
      not recognized as the cause of elevated creatinine, which in this case led to
      unnecessary hospital admission and diagnostics. This case report serves as a
      reminder for clinicians to consider hypothyroidism in the differential diagnosis
      of (sub)acute kidney injury.

PMID- 30220661
TI  - Hemothorax: a very rare complication of late diaphragmatic hernia.

PMID- 30220662
TI  - Answer to Photo Quiz: Hemothorax: a very rare complication of late diaphragmatic
      hernia.

PMID- 30220664
TI  - Answer to Photo Quiz: Swelling of the breast after cosmetic augmentation.

PMID- 30220663
TI  - Swelling of the breast after cosmetic augmentation.

PMID- 30220666
TI  - Answer to Photo Quiz: Ulcerated nodules of the tongue.

PMID- 30220665
TI  - Ulcerated nodules of the tongue.

PMID- 30220667
TI  - Q fever: hospitalisation and other concerns.

PMID- 30220668
TI  - Place of phytotherapy in the treatment of acute infections of upper respiratory
      tract and upper gastrointestinal tract.
AB  - Acute infections of the upper respiratory tract and upper gastrointestinal tract
      (mouth and throat) are still the most common reason for reporting to the general
      practitioner or ENT specialist. Despite the fact that the most common causative
      agent of these diseases is a virus, antibiotics are still flavored in about 60
      80% of patients who report to the doctor. In consensuses such as EPOS, WHO
      reports and other local/ / national reports, there is a need to limit
      antibacterial treatment for and to replace it with symptomatic and anti
      inflammatory drugs. In addition to intranasal steroids and mucocutaneous
      decongestants, supplementary treatment should be considered which resolves
      persistent symptoms. Plant preparations are used here. The growing role of
      rational phytotherapy is emphasized, especially due to the most frequent the
      etiological factor of these infections, i.e. viruses. Modern phytotherapy is a
      part of pharmacology, and all preparations based on plants meet the standards for
      of medicines and are subject to standard registration procedures. The article
      discusses the use and mechanism of action of selected herbs, among others:
      sorrel, elderberry, yarrow, and horsetail in the treatment of upper respiratory
      tract infections and upper gastrointestinal tract. The phytotherapy shows good
      efficacy and tolerance and can be used both in children and adults in recurrent
      infections of the upper respiratory tract. It is worth paying attention to the
      combined preparations, the components of which have the effects confirmed by
      randomized trials and long-term registration for use in treatment, both during
      the first signs of cold and its further duration, and supportive as support in
      chronic inflammation especially of the paranasal sinuses.

PMID- 30220669
TI  - An assessment of quality of the surgical curriculum in Pomeranian Medical
      University in years 2015-2017.
AB  - : The objective of this study was assessment of quality of the surgical
      curriculum in Pomeranian Medical University in years 2015-2017. MATERIAL AND
      METHODS: A questionnaire-survey has been conducted in a group of 100 of Polish
      students from the Medical Faculty just before the final test-exam in subject
      surgery. Main topics of the questionnaire items concerned students' opinion on
      the expected usefulness of acquired surgical knowledge for future medical
      practice, acquired manual skills, range of knowledge learned in particular
      academic years and on understanding the term "skill/competency-oriented teaching"
      surgery. RESULTS: Knowledge from general and oncologic surgery was scored by
      students the highest as potentially most useful for future medical practice.
      Learning manual skills (mostly put stiches on a pig trotter) was considered the
      most valuable portion of surgical curriculum. Acquiring of manual skills was also
      believed as the closest of meaning the term "skill/competency-oriented teaching"
      surgery. Sixth (last) year of studying was considered the most effective in
      acquiring surgical knowledge. Most responders considered time assigned for
      teaching surgery in the university curriculum adequate, but not optimally
      employed. A critical discussion of the results was done in a light of the results
      of earlier studies and the literature. CONCLUSIONS: Outcomes of this study showed
      the students' expectations in teaching surgery in the medical university
      curriculum and what was a grade of its performance. Awareness of this may have
      effect on modification of the curriculum and methods of undergraduate teaching
      surgery.

PMID- 30220670
TI  - IgG4-related disease manifesting as an isolated gastric lesion- a literature
      review.
AB  - INTRODUCTION: IgG4-related disease (IgG4-RD) is a newly recognised disorder of
      unknown etiology and pathogenesis, characterised by dense IgG4+ cells
      infiltration and fibrosis. IgG4-RD can affect various organs, but
      gastrointestinal tract involvement is rare. First case of isolated gastric IgG4
      RD reported in polish population was diagnosed in our Clinic and became the
      reason for conducting a literature review. MATERIALS AND METHODS: A literature
      review was performed using PubMed database. Eight studies of isolated gastric
      IgG4-RD, published between 2011 and 2017, and a case diagnosed by the authors
      were included. RESULTS: Three out of nine analysed patients had gastrointestinal
      complaints. In other cases lesions were detected accidentally. The majority of
      them were submucosal tumors while only one was a gastric ulcer. The most commonly
      affected was the stomach body. In all cases malignancy had been suspected, and
      the lesions were surgically removed. Diagnosis was based on the histopathology
      image and immunohistochemical staining. Only one patient had elevated IgG4 serum
      level. No case of recurrence or other organ involvement was reported. CONCLUSION:
      IgG4-related disease may manifest as an isolated gastric lesion and should be
      taken in consideration in differential diagnosis. Making an ultimate diagnosis
      without histopathological specimen examination seems to be difficult and can lead
      to misdiagnosis followed by inappropriate treatment. IgG4-RD responds well to
      steroid therapy. However, on this matter further studies are needed.

PMID- 30220671
TI  - Three-year (2014-2016) activity report of the Replantation Service for hand
      amputations in Poland.
AB  - The paper summarizes 32 months (January 2014 - August 2016) of activity of the
      Replantation Service for hand amputation in Poland. Over this period a total of
      568 cases of total and subtotal amputations as well as other complex injuries to
      the hand were referred. Of these, 354 referrals (62%) were accepted and 214 (38%)
      rejected. Among accepted, there were 167 total (47%) and 142 subtotal (40%)
      amputations; 45 patients (13%) had other severe hand injuries. Vast majority of
      the patients constituted males aged a mean of 39 years. The most common injury
      was amputation of several digits in one patient, and thumb amputation - a total
      of 229 cases (65%), followed by transmetacarpal and wrist amputations - 92 (30%)
      and forearm/arm amputations - 33 cases (9%). Replantation of amputated extremity
      was performed in 141 patients (40%), revascularization in 145 (41%) and in 29
      (8%) primary repair of the complex injuries. In 27 cases (8%), a coverage of the
      tissue defects, and in 12 (3%) primary terminalization was performed. Survival
      rate was of 78% for replantation and revascularization. Comparing to the period
      2010-2012, an increase in number of treated patients (of n=64 cases), in number
      of amputations (of 96 cases) and in number of amputated digits (of 88 cases) were
      noted. The activity report shows importance of Replantation Service, an informal
      structure, in saving limbs of severely mutilated patients.

PMID- 30220672
TI  - Colorectal surgery in elderly population.
AB  - INTRODUCTION: With the rising number of elderly patients and increasing incidence
      of colorectal cancer, management of geriatric patients has become the forefront
      of colorectal surgery. OBJECTIVES: This study aimed to investigate the short-term
      surgical outcomes following colorectal resection in elderly patients. MATERIALS
      AND METHODS: A total of 464 patients who underwent surgical resection for
      colorectal tumor between 2013 and 2017 were included. The patients were divided
      into elderly (>=75 years) and young (<75 years) group. The clinicopathological
      data of the patients were reviewed retrospectively. RESULTS: The elderly group
      constituted 30% of study population. More patients in elderly group underwent
      Hartmann procedure (p=0.02) and right hemicolectomy (p=0.029), and younger
      patients more often received low anterior resection (p=0.027). The surgical
      procedure took a shorter time in elderly group (p<0.01) but they stayed in the
      hospital one day longer (p=0.023). Postoperative complications and mortality
      tended to be higher in seniors (p=0.088). The younger patients showed a tendency
      towards a higher rate of distant metastases (p=0.053). Seniors received fewer
      preoperative chemoradiation than the young group (p=0.014). CONCLUSION: Older
      persons constitute one-third of patients treated electively in colorectal
      departments. Colorectal surgery in geriatric patients is associated with a
      prolonged hospital stay and a higher potential for complications and mortality.

PMID- 30220673
TI  - Autogenous transplants of adrenal fragments in an animal model.
AB  - : Introduction Adrenal insufficiency is a typical complication after surgical
      treatment of adrenal tumors, especially after the removal of both adrenal glands.
      Human beings are not able to survive without adrenal glands and without proper
      hormonal substitution. Autotransplantation of a fragment of the adrenal gland may
      prevent this complication. This can be done by transplanting the entire adrenal
      glands or its fragment, such as the adrenal cortex cells. In the case of adrenal
      tumors, the entire adrenal gland can not be transplanted. However, it is possible
      to transplant cells from the tumor-free part. Succesful adrenal autografts may
      result in a new treatment of adrenal insufficiency. MATERIALS AND METHODS:
      Autograft transplantation was performed on 3 groups of Sprague Dawley rats. In
      the first group, physiological corticosterone concentrations were determined.
      These animals were not operated. In the second group, both adrenal glands were
      removed. Corticosterone concentrations were determined after bilateral
      adrenalectomy. The third group was divided into two parts. In the first subgroup,
      bilateral adrenalectomy was performed simultaneosly with adrenal transplant into
      the omentum. In the second subgroup, right adrenalectomy was performed
      simultaneosly with and adrenal transplant into the omentum followed a month later
      by left adrenalectomy. During the experiment, corticosterone concentrations were
      measured at 4 time points. RESULTS: The statistical difference between
      corticosterone concentrations in rats after two timed adrenalectomies and rats
      after bilateral adrenalectomy was statistically different, but these results were
      far from physiological concentrations.

PMID- 30220674
TI  - Initial experience with endoscopic sleeve gastroplasty in Poland.
AB  - INTRODUCTION: Obesity is becoming one of the major public health problems.
      Bariatric procedures are considered the most effective methods of treating this
      condition but they are costly and entail a high risk of complications. Thus,
      there is a need to look for better bariatric treatment solutions. One of the
      newest, highly promising bariatric methods is endoscopic sleeve gastroplasty
      (ESG), which is comparably effective to other bariatric procedures in terms of
      weight loss but at the same time it is much less invasive. MATERIALS AND METHODS:
      Eight obese patients underwent ESG. Under general anaesthesia, an endoscope was
      inserted into the stomach, where a row of 4-5 running stitches was placed (from
      the pyloric part towards the GE junction). Each of the stitches was cinched
      tight, which resulted in gastric lumen reduction comparable to that achieved with
      laparoscopic sleeve gastrectomy. RESULTS: The procedures were performed without
      any severe peri-operative complications. The only adverse event was a minor
      haemorrhage in one of the patients, which did not require any surgical
      intervention. After the surgery, the patients reported a substantial weight loss.
      Mean %TBWL was 8.6%, 15.4% and 19.6% at 1, 2 and 3 months, respectively.
      CONCLUSIONS: Minimally invasive and highly effective in body weight reduction,
      endoscopic sleeve gastroplasty is a promising method of treating obesity. The
      procedure requires appropriate tools and equipment. The method guarantees gastric
      volume reduction comparable to that achieved with sleeve resection. The initial
      results confirm that the effectiveness of the surgery in terms of body weight
      loss is similar to that seen in other forms of bariatric treatment. DISCUSSION:
      Compared to laparoscopic sleeve gastrectomy, endoscopic sleeve gastroplasty is
      substantially less invasive. Also, it requires shorter procedure time and shorter
      hospital stay. Data from other medical centres demonstrate somewhat lower
      dynamics of total body weight loss but these results need to be verified in a
      long-term follow-up.

PMID- 30220675
TI  - Perioperative calcium and vitamin D supplementation in patients undergoing
      thyroidectomy - literature review.
AB  - : Sentence recommending the content of work: Due to the health and economic
      consequences of postoperative hypocalcemia, it is necessary to disseminate
      knowledge about non-invasive methods of limiting it that can be used in everyday
      clinical practice such as routine perioperative calcium and vitamin D
      supplementation. Abstract Introduction: Postoperative hypocalcemia is a narrow
      but significant problem for patients undergoing thyroid and parathyroid surgery.
      It is the most common complication after thyroidectomy. It is associated with
      transient or permanent hypoparathyroidism. It could potentially be life
      threatening for patients and increases the costs of hospitalization. The aim of
      the study was to evaluate the results of studies that routinely administrated
      calcium and/ or vitamin D during the postoperative period. MATERIALS AND METHODS:
      In this article, a literature review - 15 studies that used routine perioperative
      calcium (7 studies), vitamin D (2 studies) and calcium with vitamin D (11
      studies) supplementation was performed. Supplementation effectiveness in
      prevention of postoperative hypocalcemia was compared to no prophylaxis in 10
      studies. Five studies compared the effect of combined administration (calcium and
      vitamin D) to calcium alone. The number of works dealing with this problem is not
      particularly large. RESULTS: Supplementation significantly decreased the rate of
      laboratory and symptomatic hypocalcemia. It was also effective in reducing the
      severity of symptoms. The combination calcium with vitamin D was the most
      effective strategy. No hypercalcemia or parathyroid hormone inhibition was
      observed in the supplemented groups. Routine supplementation was less expensive
      than performing laboratory tests in the course of treatment of hypocalcemia.
      CONCLUSIONS: The results of analyzed studies showed the clinical and economic
      advantage of routine perioperative prophylactic supplementation of vitamin D and/
      or calcium as compared to no prophylaxis. However, the majority of studies showed
      a significant range of variability in patients' characteristics. Numerous studies
      did not evaluated the preoperative 25-hydroxycholecalciferol level - a risk
      factor for postoperative hypocalcemia. DISCUSSION: The use of routine
      prophylactic supplementation of calcium and vitamin D in the perioperative period
      can be useful in everyday clinical practice. Further research is needed to draw
      clear guidelines regarding prophylactic calcium and vitamin D therapy for
      patients after thyroidectomy.

PMID- 30220676
TI  - Incidence, morbidity and 5-year survival of colorectal cancer patients in the
      Kujawsko-Pomorskie voivodship in 2005-2011, based on data from the National
      Health Fund.
AB  - INTRODUCTION: The incidence, morbidity and 5-year survival rates illustrate the
      epidemiological situation of colorectal cancer and assess the effectiveness of
      the treatment. In Poland, the National Health Fund is the payer of benefits. The
      data related to morbidity, incidence, and 5-year survival may be supplementary to
      the epidemiological data of the National Cancer Registry. OBJECTIVE: Analysis of
      benefits granted by NHF in Bydgoszcz to persons with diagnosed colorectal cancer
      in 2006-2011 including the assessment of incidence, morbidity and 5-year survival
      of the population in the Kujawsko-Pomorskie province. MATERIAL AND METHODS: The
      study analyzed the benefits recorded in the database of the National Health Fund
      in Bydgoszcz in 2006-2011 given to patients with colorectal cancer. The Kaplan
      Meier method and the gambling rate were used to determine the probability of
      survival. RESULTS: In 2006-2011 men were offered 10.1% more benefits than women.
      The most frequent benefits were colorectal cancer (48.9%), rectal cancer (43.8%)
      and esophageal cancer (7.2%). In total, 50410 benefits were provided. Despite the
      increase in the number of women in the population, 388 more men died than women.
      The probability of survival was 46.8 %% and 42.6% for men and women,
      respectively, and 41.8%, 44.2% and 48.9% for colon cancer, esophageal and rectal
      folds, respectively. CONCLUSIONS: In the Kujawsko-Pomorskie province during the
      period of 2006-2011 the number of diagnosed colorectal cancers increased as did
      the overall number of benefits provided.There was also a downward trend for the
      total number of benefits granted in relation to the trend of the increase in the
      number of new diagnosed cases. Incidence and morbidity rates were variable,
      gradually increasing in subsequent years and amounted to 59/100000 and 67/100000,
      355/100000 and 408/100000 in 2010 and 2011, respectively. The probability of 5
      year survival was 45.2%. Diagnosis of a disease in patients above 69 years of age
      increased the likelihood of death.

PMID- 30220677
TI  - Determination of selected dynamic quantities of growing intact seeds of maize.
AB  - Plant growth and intracellular H+ ion kinetics are known to be strictly
      correlated, although the history of this discovery, which is known as the acid
      growth hypothesis, has faced many difficulties and provoked a long-lasting
      discussion. Simultaneous measurements of the plant cell extension and pH of the
      incubation medium helped to defend the theory and together with some of the
      newest physics-based models, offered a new insight at the molecular level. This
      article focuses on both the biological and physical aspects of plant growth in
      the presence of endogenous auxin. Our aim was to circumvent the experimental and
      conceptual pitfalls associated with the standard use of cut and/or abraded
      coleoptile segments. Therefore, we simultaneously investigated the growth of
      intact seedlings of maize (Zea mays L.) and pH of the incubation medium. The
      growth rates were measured by applying a non-invasive technique that records time
      lapse images of the macroscopic elongation of the coleoptiles, while changes in
      the pH were monitored using a pH/Ion meter. In the experiments, we intentionally
      introduced growth stimulators: indole-3-acetic acid (IAA), fusicoccin (FC),
      gibberellic acid (GA3), and a growth inhibitor cadmium chloride (CdCl2), in order
      to analyse the resultant effect of both exogenous and endogenous factors.

PMID- 30220678
TI  - Crocin protects intestine tissue against carbon tetrachloride-mediated oxidative
      stress in rats.
AB  - Saffron is used in traditional medicine for its hypolipidemic, anti-inflammatory
      and anti-carcinogenic properties as a natural remedy in treatment of diseases.
      The objective of the present study was to demonstrate the protective effect of
      crocin (one of the main ingredients of saffron) on carbon tetrachloride (CCl4)
      damage in intestinal mucosa. MDA, GSH, SOD, CAT, TAS and TOS levels were measured
      in experimental animal tissue samples and these were compared with histologic
      lesions induced by CCl4. CCl4 caused an increase in MDA, SOD, CAT and TOS levels
      and a significant decrease in GSH and TAS levels in rat intestinal tracts. After
      crocin treatment, serious improvements were observed in histological lesions and
      biochemical results in the intestinal tract. In conclusion, crocin inhibited the
      toxic effects induced by CCl4 in the intestine by its strong antioxidant
      properties.

PMID- 30220679
TI  - Effects of short-term Pilates exercise on selected blood parameters.
AB  - The aim of our prospective, interventional, pre-post, single arm study was to
      supplement the lack of knowledge of the effect of short-term Pilates intervention
      on selected blood parameters of healthy women. Female volunteers were recruited
      for 2-weeks Pilates intervention. Blood has been collected and anthropometric
      parameters were measured before and after exercise period (EP). Plasma insulin,
      cortisol, and dehydroepiandrosterone sulphate levels, erythrocyte antioxidant
      activity, glutathione levels, NK cytotoxicity and plasma cytokines were analysed.
      We found a decrease in erythrocyte antioxidant enzymes SOD and GPx activity; GSH
      levels; in the pro-inflammatory chemokine MCP-1 and trend to reduction in MIP
      1beta, PDGF and VEGF levels in plasma. NK cell cytotoxic activity increased after
      Pilates EP in the percentage of specific lysis at 25:1 effector: target (E:T)
      ratio and the same trend was observed at all E:T ratios as well as in the amount
      of lytic units per 107 cells. Our findings show that Pilates exercise may improve
      NK cell immune response and inflammatory milieu in plasma of healthy women.

PMID- 30220681
TI  - Editors' Note.

PMID- 30220680
TI  - Effect of 2.45 GHz microwave radiation on the fertility pattern in male mice.
AB  - A number of studies have reported that male reproductive organs are susceptible
      to electromagnetic fields (EMFs). The aim of this study was to explore the
      effects of microwave radiation exposures on 6-8 weeks old male Swiss albino mice.
      Mice were divided into two groups: group I - sham-exposed (Control), and group II
      - microwaves-exposed (MWs). Mice were exposed to 2.45 GHz with power density 0.25
      mW/cm2 and specific absorbtion rate (SAR) 0.09 W/kg. Exposure was given in
      Plexiglas cages for 2 h/day for 30 days. Results showed that 2.45 GHz microwave
      radiation resulted in a significant increase (p < 0.001) in catalase (CAT),
      malondialdehyde (MDA), reactive oxygen species (ROS) and decrease (p < 0.001) in
      the levels of glutathione peroxidase (GPx), testosterone and superoxide dismutase
      (SOD) (p < 0.05). Flow cytometer analysis of blood showed the formation of
      micronuclei in microwave-exposed group. Histopathological changes were also seen
      in seminiferous tubules of microwave-exposed group as compared to the sham
      exposed group. It is concluded that 2.45 GHz microwave radiation exposure causes
      oxidative stress in testes and it may lead to detrimental and injurious effects
      on fertility potential of the male reproductive system of Swiss albino mice.

PMID- 30220683
TI  - If We Had Known.

PMID- 30220684
TI  - Healthcare Challenges of an Adoptee.

PMID- 30220682
TI  - Healthcare Challenges Faced by Adopted Persons Lacking Family Health History
      Information.
AB  - An individual's genetic-relative family health history can lead to the
      identification of high-risk individuals and through this can result in highly
      effective disease prevention for those at risk. In this symposium, readers will
      see the very different lived experiences of adopted persons whose access to
      genetic-relative family health history is limited. All share a common experience
      of facing obstacles within the U.S. healthcare system related to lacking family
      health history. Genomic technologies now offer tremendous promise to fill gaps in
      access to this vital health information.

PMID- 30220685
TI  - An Unfinished Story, an Unfinished Body: How Missing Health Histories Predispose
      Adoptees to Illness.

PMID- 30220686
TI  - A Tale of Two (Adopted) Sisters.

PMID- 30220687
TI  - When Health History is a Matter of Life or Death.

PMID- 30220688
TI  - A Personal Reflection on the Medical History Questions facing Adopted Persons.

PMID- 30220689
TI  - My Heart Beats with Gratitude.

PMID- 30220691
TI  - Adoption Times Two.

PMID- 30220690
TI  - A Genome of One.

PMID- 30220692
TI  - Chest Pain.

PMID- 30220693
TI  - Limited Medical History: An Adoption Story.

PMID- 30220694
TI  - The Presence of Absence.

PMID- 30220695
TI  - An Unfinished Puzzle.

PMID- 30220697
TI  - Claiming What Is Rightfully Mine.
AB  - Although adopted persons did not choose to be adopted, their life-long task is to
      come to terms with its meaning, which includes absence of important information
      about their family health history. Problematic encounters with health care
      professionals inspired contributors' narratives recognizing compelling need for
      accurate information about themselves as well as access to empathic and
      resourceful medical professionals. A key issue pervading the narratives was loss:
      loss of birth name and identity, loss of birth relatives and history, and often
      loss of birth culture. In response to this deeply felt sense of loss, many
      authors expressed the need to claim what they believe to be rightfully theirs,
      namely, information about their own history. Policy and practice recommendations
      regarding training of health care professionals as well as access to original
      birth records and ongoing family health information are discussed.

PMID- 30220696
TI  - Adoptees' Pursuit of Genomic Testing to Fill Gaps in Family Health History and
      Reduce Healthcare Disparity.
AB  - In the symposium of stories by adoptees who have faced health issues without
      family health history information, genomic testing is considered as a potentially
      life-saving means for adoptees to obtain family medical information. The authors
      share feelings of loss, frustration in healthcare settings, fear of unknown
      genetic susceptibility to disease, desire for knowledge and self-empowerment in
      medical decision making, and uncertainty about the utility of genomic testing.
      Adoptees may pursue ancestry testing, genetic genealogy to find biological
      relatives, and medical genomic testing. They may choose direct-to-consumer
      testing because of its affordability and accessibility. Adopted persons are
      gaining support from healthcare professionals in their pursuit of genomic
      testing. The National Society of Genetic Counselors' position statement regarding
      genetic testing and adoption "supports consideration of genetic testing,
      including genome-wide testing, for adopted adults." However, predictive genomic
      testing of children in the adoption process is not recommended by the NSGC unless
      testing may affect childhood medical management. The American Society of Human
      Genetics and the American College of Medical Genetics and Genomics similarly
      recommend that genetic testing of children in the adoption process be limited to
      diagnostic testing for conditions for which there is timely preventative or
      therapeutic intervention. Going forward, there is responsibility and opportunity
      for national genetics and genomics societies and healthcare systems to hone their
      practice guidelines for genomic testing for adoptees. A successful approach will
      include evidence-based guidelines for genomic testing, inclusion of genetic
      counseling before and after testing, and return of genomic test results to
      adoptees' medical homes.

PMID- 30220698
TI  - Family Health History: Invaluable for Adoptees' Medical Care and Self Identity.
AB  - Adoption is one of several ways to have a family. Adoption is unique in that it
      involves birth parents, adoptive parents, and adoptees. For many adoptees, there
      is no information about their birth family health history which can create
      healthcare challenges. In these narratives, many adoptees discuss genetic testing
      as a substitution for their birth family health history which is one common theme
      in these stories. However, two narratives illustrate the value of an on-going
      family health history with birth families to identify health risks that are not
      identified in genetic testing but evolve over time. Another theme in these
      narratives is the adoptees' feeling of loss and their search for self-identity.
      For some adoptees this sense of loss never goes away and leaves them with an
      incomplete identity. Society, but especially adoptive parents, should help
      adoptees' in this search to help them cope with the sense of loss and
      incompleteness adoption can create and form a healthy self-identity.

PMID- 30220699
TI  - Reinforcing Loss and Rendering Invisible: Adoptee Experience and the Structural
      Failings of Biomedicine.
AB  - This commentary discusses the challenge of health care interactions for people
      who are adopted. These narratives describing how adoptees approach and are
      approached by biomedicine make it clear that their needs are not being met and
      that many feel ostracized in clinical encounters. I argue that adoptee identity
      should be included along with categories such as race, class and gender when we
      consider intersectional approaches to health and healthcare. We cannot consider a
      one-size fits all approach to health care for adoptees, as these stories make
      clear that a lack of known family history should neither preclude adoptees from
      accessing tests and services, nor serve as an automatic indication for heightened
      screening. There is a need for structural changes to biomedicine that would allow
      for alternatives to family history in considering the diagnosis, treatment and
      prevention of disease.

PMID- 30220700
TI  - Comparing Patient, Clinician, and Caregiver Perceptions of Care for Early
      Psychosis: A Free Listing Study.
AB  - Models for early psychosis intervention often involve shared decision-making
      among patients, their caregivers, and clinicians. However, this process rests on
      a shared understanding of constructs, experiences, and language. This study
      examined how various aspects of early psychosis care were conceptualized by those
      involved in the help-seeking process, and the extent to which their perceptions
      aligned with one another. We conducted a free listing study to systematically
      explore perceptions of the help-seeking process and management of psychosis
      related symptoms among a sample of 65 patients, caregivers, and clinicians at an
      early psychosis intervention clinic. Results indicated varying levels of
      agreement between different roles on getting or giving help, taking medications,
      factors influencing symptom management, and thoughts regarding the future. These
      findings highlight important differences and emphasize a need for further
      exploration of how stakeholder perceptions may influence decisions surrounding
      the care of individuals experiencing early psychosis.

PMID- 30220701
TI  - The Will Reconsidered: Hard Choices in Living Organ Donation.
AB  - In the following article, we illustrate an interview between a living donor
      advocate and a potential living organ donor in which the donor faced a hard
      choice: the reasons to donate and the reasons not to donate were equally
      persuasive. In the discussion that follows, we analyze the act of willing, what
      differentiates coercion and willing, and how the case study highlights a
      different, but by no means rare, instance in which donors feel paralyzed by the
      choice at hand. In such cases, we suspect that donor advocates either do not
      approve the potential donor for transplantation or simply remain neutral. But we
      think that this approach benefits neither the donor nor the recipient. We
      conclude this study with recommendations for living donor advocates, providing
      questions that might solicit donors' deeper values and suggesting that in these
      situations donors may benefit from additional time for reflection.

PMID- 30220702
TI  - Effect of Phacoemulsification on Visual Acuity and Macular Morphology in Patients
      with Wet Age-Related Macular Degeneration.
AB  - BACKGROUND This article discusses the effectiveness of phacoemulsification
      cataract surgery with intraocular lens implantation in patients with wet age
      related macular degeneration in the inactive phase of the disease. MATERIAL AND
      METHODS Forty-nine patients (50 eyes) aged 78.94+/-5.54 years, previously treated
      with intravitreal injections of anti-vascular endothelial growth factor agents,
      were qualified for a prospective, randomized 12-month study. The participants
      were divided into 2 groups. Group I consisted of 25 patients (25 eyes) who were
      subjected to phacoemulsification cataract surgery. Group II consisted of 24
      patients (25 eyes) who were not subjected to phacoemulsification cataract surgery
      despite having a lens opacity of grade II or higher according to the Lens
      Opacities Classification System. RESULTS After 12 months of follow-up, patients
      in group I gained on average 8.04 letters (p<0.001). Furthermore, 20% of the eyes
      had a significant improvement in best corrected visual acuity of >=15 Early
      Treatment of Diabetic Retinopathy Study Chart letters. Patients in group II lost
      on average 1.96 letters (p>0.05). No significant differences between central
      retinal thickness values in either group (p>0.05) were noted. The mean number of
      intravitreal injections of anti-vascular endothelial growth factor agents during
      the study was 2.64+/-1.98 in group I and 2.92+/-2.40 in group II (p>0.05).
      CONCLUSIONS Phacoemulsification performed in eyes with wet age-related macular
      degeneration during the inactive phase of the disease significantly improves
      visual acuity. In addition, it does not significantly influence the frequency of
      intravitreal injections of anti-vascular endothelial growth factor agents or
      disease activity.

PMID- 30220703
TI  - Central Nervous System Bleeding After a Lumbar Puncture: Still an Ongoing
      Complication.
AB  - BACKGROUND A lumbar puncture is a procedure performed to uncover the state of the
      central nervous system by analysis of the cerebrospinal fluid. It is done also to
      infuse medications in the subdural space. A lumbar puncture should not cause
      central nervous system bleeding, but this complication is still occurring in
      certain cases. CASE REPORT We present 2 cases where a lumbar puncture was
      performed in the emergency department. The first patient had severe inflammatory
      lower back pain and received epidural steroids through a lumbar puncture and the
      second case presented with the clinical picture of meningitis and a lumbar
      puncture was performed for diagnostic purposes. In both cases, major
      complications arose secondary to bleeding in the cerebrospinal fluid. The first
      case developed a bleeding tendency because the patient had acute renal failure
      and was on low molecular weight heparin. The second case had low platelet count
      because of myelodysplasia. Both cases bled into the subarachnoid space and
      subdural space resulting in compression of the cauda equine and paralysis. The
      bleeding eventually flowed into the posterior fossa resulting in vasospasm of the
      posterior circulation and infarction of the posterior cerebral arteries.
      CONCLUSIONS We concluded that both patients sustained complications from the
      lumbar puncture because of a bleeding tendency secondary to systemic illnesses
      and multiple drugs and their side effects. We recommend that patients' medical
      condition be well evaluated, and proper blood studies be performed prior to
      lumbar punctures to avoid major morbidities.

PMID- 30220704
TI  - Chromosomal Processes in Mind-Body Medicine: Chronic Stress, Cell Aging, and
      Telomere Length.
AB  - Stress affects cellular aging and inflammatory and chromosomal processes,
      including telomere length, thereby potentially compromising health and
      facilitating disease onset and progression. Stress-related diseases and
      strategies to manage stress usually require integrative or behavioral therapeutic
      approaches that also operate on cellular levels. Mind-body medicine (MBM) uses
      the interaction between the mind, body, behavior, and the environment to correct
      physical and psychological malfunctions, thus ameliorating disease states and
      improving health. The relaxation response (RR) is a physiological opponent of
      stress and the stress response (SR) (i.e., fight-or-flight response), also
      invoking molecular anti-stress processes. Techniques that elicit the RR are at
      the core of practically all MBM interventions. We surmise that these techniques
      can also affect chromosomal and telomere processes, molecular aging, and the
      modulation of inflammatory states on cellular levels.

PMID- 30220705
TI  - Independent validation of the PREDICT breast cancer prognosis prediction tool in
      45,789 patients using Scottish Cancer Registry data.
AB  - BACKGROUND: PREDICT is a widely used online prognostication and treatment benefit
      tool for patients with early stage breast cancer. The aim of this study was to
      conduct an independent validation exercise of the most up-to-date version of the
      PREDICT algorithm (version 2) using real-world outcomes from the Scottish
      population of women with breast cancer. METHODS: Patient data were obtained for
      all Scottish Cancer Registry (SCR) records with a diagnosis of primary invasive
      breast cancer diagnosed in the period between January 2001 and December 2015.
      Prognostic scores were calculated using the PREDICT version 2 algorithm. External
      validity was assessed by statistical analysis of discrimination and calibration.
      Discrimination was assessed by area under the receiver-operator curve (AUC).
      Calibration was assessed by comparing the predicted number of deaths to the
      observed number of deaths across relevant sub-groups. RESULTS: A total of 45,789
      eligible cases were selected from 61,437 individual records. AUC statistics
      ranged from 0.74 to 0.77. Calibration results showed relatively close agreement
      between predicted and observed deaths. The 5-year complete follow-up sample
      reported some overestimation (11.5%), while the 10-year complete follow-up sample
      displayed more limited overestimation (1.7%). CONCLUSIONS: Validation results
      suggest that the PREDICT tool remains essentially relevant for contemporary
      patients with early stage breast cancer.

PMID- 30220706
TI  - Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p.
AB  - BACKGROUND: Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are
      progenitor cells shown to migrate to the tumour and participate in the tumour
      microenvironment. BM-MSCs play important roles in tumour processes through the
      release of cytokines or exosomes; however, how BM-MSCs influence the stemness of
      CSCs in colon cancer cells remains poorly understood. METHODS: We isolated
      exosomes from BM-MSCs and used these exosomes to treat colon cancer cells (HCT
      116, HT-29 and SW-480). We compared stemness traits of colon CSCs by cell surface
      marker (CD133 and Lgr5) and functional assays, such as chemoresistance, colony
      formation, cell adhesion, invasion and tumour-formation assay. We performed a
      microRNA array to investigate the differences in exosomal microRNA expression
      between colon cancer cells, BM-MSCs and co-cultured cells and performed
      functional and molecular analysis of the gene targets. RESULTS: In this study, we
      found that BM-MSC-derived exosomes contained distinct microRNAs, including miR
      142-3p, which in turn increased the population of CSCs in colon cancer cells.
      Depriving miR-142-3p from BM-MSC-derived exosomes clearly decreased the
      population of colon CSCs. Mechanistically, Numb was found to be the target gene
      of miR-142-3p, and miR-142-3p promoted the Notch signalling pathway by
      downregulating Numb. CONCLUSIONS: Our findings indicate that BM-MSC-derived
      exosomes promote colon cancer stem cell-like traits via miR-142-3p.

PMID- 30220707
TI  - Brief Report: Potent clinical and radiological response to larotrectinib in TRK
      fusion-driven high-grade glioma.
AB  - Genes encoding TRK are oncogenic drivers in multiple tumour types including
      infantile fibrosarcoma, papillary thyroid cancer and high-grade gliomas (HGG).
      TRK fusions have a critical role in tumourigenesis in 40% of infant HGG. Here we
      report the first case of a TRK fusion-driven HGG treated with larotrectinib-the
      first selective pan-TRK inhibitor in clinical development. This 3-year-old girl
      had failed multiple therapies including chemotherapy and radiotherapy. Tumour
      profiling confirmed an ETV6-NTRK3 fusion. Treatment with larotrectinib led to
      rapid clinical improvement with near total resolution of primary and metastatic
      lesions on MRI imaging. This is the first report of a TRK fusion glioma
      successfully treated with a TRK inhibitor.

PMID- 30220708
TI  - Everolimus and pazopanib (E/P) benefit genomically selected patients with
      metastatic urothelial carcinoma.
AB  - BACKGROUND: Metastatic urothelial carcinoma (mUC) is a genomically diverse
      disease with known alterations in the mTOR pathway and tyrosine kinases including
      FGFR. We investigated the efficacy and safety of combination treatment with
      everolimus and pazopanib (E/P) in genomically profiled patients with mUC.
      METHODS: mUC patients enrolled on a Phase I dose escalation study and an
      expansion cohort treated with E/P were included. The primary end point was
      objective response rate (ORR); secondary end points were safety, duration of
      response (DOR), progression-free survival (PFS) and overall survival (OS).
      Patients were assessed for mutations and copy number alterations in 300 relevant
      cancer-associated genes using next-generation sequencing and findings were
      correlated with outcomes. Time-to-event data were estimated with Kaplan-Meier
      methods. RESULTS: Of the 23 patients enrolled overall, 19 had mUC. ORR was 21%
      (one complete response (CR), three partial responses (PR), eight with stable
      disease (SD). DOR, PFS and OS were 6.5, 3.6, and 9.1 months, respectively. Four
      patients with clinical benefit (one CR, two PR, one SD) had mutations in
      TSC1/TSC2 or mTOR and a 5th patient with PR had a FGFR3-TACC3 fusion.
      CONCLUSIONS: Combination therapy with E/P is safe in mUC and select patients with
      alterations in mTOR or FGFR pathways derive significant clinical benefit.

PMID- 30220709
TI  - Effects of magnetostimulation on muscle activity and pain in edentulous adults
      with temporomandibular disorders.
AB  - INTRODUCTION: Multifactorial aetiologies of painful temporomandibular disorders
      (TMD) have an impact on correct diagnosis and consequently prevent proper
      treatment. AIM OF THE STUDY: The aim of the study was to evaluate the effect of
      magnetic stimulation on electromyographic activity in temporal muscles and
      masseters in patients using occlusal splints. MATERIALS AND METHODS: The examined
      group consisted of 40 edentulous patients with TMD. The patients were examined
      based on Helkimo Index. Next, electromyographic activity of the temporal muscle
      and masseter were investigated using 8-channel surface electromyography. All
      patients received acrylic occlusal splints for 12 weeks. The group qualified for
      the study included 20 randomized patients, whose therapy was additionally carried
      out by extremely low-frequency magnetic fields for a period of 21 days. Following
      examinations were conducted after 3, 6 and 12 weeks with surface electromyography
      recording of the examined muscles. Patients received occlusal splint corrections
      using the T-Scan III system. The clinical evaluation of TMD was analysed using
      Helkimo index and VAS scale before and after the treatment. All the data were
      analysed using Statistica 12.5 PL. RESULTS: Patients with combination therapy had
      lower asymmetry of temporal muscle activity. CONCLUSIONS: Combination therapy
      using magnetic stimulation reduced intensity of pain in patients with TMD and
      decreased values of the Helkimo indices.

PMID- 30220710
TI  - Quiet standing postural sway of 10- to 13-year-old, national-level, female
      acrobatic gymnasts.
AB  - PURPOSE: The aim of the study was to determine whether 10- to 13-year-old,
      national-level, female acrobatic gymnasts present a different quiet standing
      postural control (with and without visual cues) than untrained female peers.
      METHODS: The mean velocity of the center of pressure (in anterior-posterior and
      medial-lateral directions) was computed from 60-s long quiet-standing trials on a
      stationary force plate in fifteen 10- to 13-year-old female acrobatic gymnasts
      and thirteen sex- and age-matched non-athletes. A two-way repeated measures ANOVA
      (acrobatic gymnasts vs. non-athletes and eyes open vs. eyes closed) was used for
      the anterior-posterior and mediallateral COP mean velocity. The relation between
      subjects' body mass and COP mean velocity was tested with the used Spearman's
      Rank Correlation Coefficient. RESULTS: Postural sway (represented by COP mean
      velocity) was not significantly different between the acrobatic gymnasts and the
      non-athletes ( p > 0.05), except for the faster medial-lateral sway in eyes-open
      conditions in the acrobatic gymnasts ( p < 0.05). The gymnasts' body mass
      negatively correlated with their anterior-posterior sway velocity in both visual
      conditions (eyes open: r = -0.7; eyes closed: r = -0.6) and with medial-lateral
      sway velocity during eyes-closed trials (r = -0.5; p < 0.05). CONCLUSIONS:
      Results of the study indicate that in quiet standing postural control 10- to 13
      year-old acrobatic gymnasts did not make use of their trained abilities. Heavier
      gymnasts might have been more stable than lighter ones during quiet standing.

PMID- 30220711
TI  - Excessive tensile strain induced the change in chondrocyte phenotype.
AB  - PURPOSE: Chondrocyte extracellular matrix type II collagen and proteoglycans
      ensure an important compression-bearing structure in synovial joint. However,
      much more type I collagen is generated in osteoarthritis, which implies the
      presence of abnormal tensile strain in cartilage. We hypothesize that tensile
      stress influences chondrocyte phenotype at the cellular level, leading to
      potential osteoarthritis. METHODS: Chondrocytes were stimulated with cyclic
      excessive tensile (10%) or mild tensile or compressive strain (5%) at 0.5 Hz, 3 h
      per day for 3 days. Chondrocyte morphology and matrix proteoglycans level was
      separately determined by Rhodamine phalloidin and toluidine blue staining. The
      expression of cartilage marker molecules was measured using quantitative reverse
      transcription polymerase chain reaction and enzyme-linked immunosorbent assays.
      RESULTS: Chondrocytes demonstrated significant fibroblastic morphology, reduced
      proliferation and increased apoptosis following exposure to 10% tensile strain.
      The 10% tensile strain group induced the lowest matrix proteoglycans level. It
      observably reduced the expression of COL2A1, Acan and SOX9, and increased COL1A1
      expression level. The 5% tensile (5% compression) group, maintained the
      chondrocyte phenotype. CONCLUSIONS: The findings identified the effects of
      different magnitudes of tensile stress on chondrocyte phenotype compared to
      compressive strain. Further studies on cartilage biomechanical micro-environment
      might benefit from this study.

PMID- 30220712
TI  - Three-dimensional biomechanical modeling and simulation of trephine cutting
      cornea for keratoplasty.
AB  - PURPOSE: Trephination is one of the basic operations of keratoplasty, and the
      biomechanical mechanism of the operation can be revealed based on three
      dimensional modeling and simulation of trephine cutting cornea. METHODS: Based on
      the analysis of the physical and biomechanical characteristics of corneal
      trephination, a three-dimensional numerical model of corneal trephination is
      built, where the cornea can be simplified to two layers structure including
      stroma and epithelium, and the trephine cuts the cornea under the vertical motion
      load and the rotational motion load. A three-dimensional failure criterion of
      corneal material is proposed based on the yield strength theory. On this basis,
      trephination simulation is carried out, and the units of corneal material are
      removed from the model when they meet the defined failure criterion. RESULTS:
      Under the given parameters including the velocity, the angle and the angular
      velocity, the trephine force curves, include the linear cutting force and the
      rotary cutting force are obtained, and show the change of the forces with
      displacement during the process of trephination simulation. The maps of the
      equivalent stress show the destruction and deformation of the cornea. Then, the
      experiment of robotic trephination is carried out under the same parameters and
      the effectiveness of the simulation is evaluated. CONCLUSIONS: Based on mechanics
      theory and finite element method, the process of trephine cutting cornea has been
      reproduced, and the interaction mechanism is revealed, which lays the foundation
      for the development of real-time simulation and virtual system of the corneal
      surgery.

PMID- 30220713
TI  - Effect of porosity on the structure, mechanical properties and cell viability of
      new bioceramics as potential bone graft substitutes.
AB  - Porous and alternative biografts for possible usages in orthopaedic applications
      were synthesized by the substitution of gelatin (G), cuttlefish backbone (C),
      meerschaum sepiolite (S) and hydroxyapatite (H). The effects of different
      proportions of the Gelatin substitutions on the mechanical properties and
      structure and cell viability properties of the fabricated biografts were
      investigated. Throughout the structure and mechanical evaluations, it was found
      that Gelatin substitution in the fabricated biografts increased the total
      porosity fraction, particularly for C13G75 and S13G75 biografts. Scanning
      Electron Microscope (SEM), X-ray diffraction (XRD) and Fourier Transform Infrared
      Spectroscopy (FTIR) were used for characterization of the synthesized biografts.
      Furthermore, the cell viability tests for the synthesized biografts were carried
      out by using the osteoblast cell culture. Throughout the analysis, the
      synthesized C13G75 and S13G75 biografts generated the highest porosity and better
      correlation between mechanical properties and structural results contributing
      with highest cell viability rates.

PMID- 30220714
TI  - Thermovision analysis of surface body temperature changes after thermal
      stimulation treatments in healthy men.
AB  - PURPOSE: Among thermal stimulation treatments that have a beneficial effect on
      the human body general application of cold and various forms of massage are
      mentioned which can be assessed by means of thermovision analysis. The aim of the
      study was to evaluate changes in the distribution of surface body temperature
      under the influence of whole-body cryostimulation, classical massage and hot
      stone massage. MATERIALS AND METHODS: The study was conducted on a group of 40
      men aged 20-24 years. They were subjected to a cryostimulation treatment at -120 
      degrees C and -140  degrees C, and to heat-stimulating treatments in the form of
      massages. Before the treatment, blood pressure and heart rate were measured.
      Temperature distribution in the 12 areas of the body surface was recorded using a
      Thermo Vision A20M Thermo Vision Camera with Therma CAM Researcher 2.8 software.
      RESULTS: Statistically significant differences between cryostimulation treatments
      in the left upper limb and the back of the trunk were found. After heat
      stimulating treatments, a statistically significant increase in temperature after
      classic massage was observed in the lower limbs, and a similar increase in
      temperature was noted in the rear of the pectoral girdle and of the trunk after
      hot stone massage. CONCLUSIONS: The thermovision analysis showed a great
      variation of body surface temperature depending on the body area. The higher
      changes in temperature, of up to 20%, were found within the upper and lower
      extremities in the group treated with cryostimulation. After heat-stimulating
      treatments, lower temperature differences, of 2-6%, were observed, the largest
      within the trunk and the lower limbs.

PMID- 30220715
TI  - Balance in handstand and postural stability in standing position in athletes
      practicing gymnastics.
AB  - PURPOSE: The aim of this study was to compare and analyse of relationships
      between stability indices registered in two positions: standing and handstand in
      athletes practicing gymnastics at various levels of advancement. METHODS: The
      study included 46 athletes practicing gymnastics. The research tool was
      posturograph CQ-Stab 2P. RESULTS: In both standing position and handstand in the
      seniors there were statistically significantly lower values of such indicators
      as: sway area delimited by the center of pressure ( p = 0.004, p = 0.014), mean
      amplitude of COP ( p = 0.021, p = 0.017), mean displacement of the center of
      feet/hands pressure in medio-lateral direction ( p = 0.011, p = 0.003) and
      maximal displacement of the center of feet/hands pressure in mediolateral
      direction ( p = 0.036, p = 0.036). In the standing position, seniors also had
      statistically significantly lower values of the statokinesiogram path length,
      both total ( p = 0.000) as well as in anteroposterior ( p = 0.001) and
      mediolateral ( p = 0.002) directions. In the seniors group there were
      statistically significant correlations between variables obtained in standing
      position and handstand. CONCLUSIONS: The level of sport advancement significantly
      differentiates the stability of a body in standing position and handstand. The
      seniors practicing gymnastics, compared to juniors, are characterized by a better
      ability to control the position of the body in both positions. The lack of
      relationships between stability indices registered in standing and handstand in
      juniors suggests that the analysis of the values of stability indices obtained in
      a standing position does not provide the possibility of predicting the ability to
      maintain balance in the handstand during the recruitment of candidates for
      gymnastics.

PMID- 30220716
TI  - The use of the Gait Variability Index for the evaluation of individuals after a
      stroke.
AB  - PURPOSE: The Gait Variability Index (GVI) summarizes overall gait quality, taking
      into account spatiotemporal parameters from a 3-dimensional gait analysis.
      However, there are no studies evaluating changes in gait patterns after stroke,
      based on the GVI. The study was designed to assess usefulness of the GVI for
      evaluation of gait pathology in subjects with stroke, compared to healthy
      individuals. METHODS: Spatiotemporal gait parameters were examined in a group of
      50 subjects at a chronic stage post-stroke and in 50 healthy controls. The GVI
      was calculated based on the 9 spatiotemporal data. RESULTS: The findings show
      statistically significant differences between the values of the GVI for paretic
      and non-paretic limbs ( p < 0.001). Higher values of the index were identified in
      the case of non-paretic limb: 80.74 vs. 76.32. The GVI scores were decreased for
      both paretic and non-paretic limbs, compared to the controls - p < 0.001.
      CONCLUSIONS: The GDI score seems to be a viable tool for quantifying changes in
      gait pattern during evaluation of subjects with chronic post-stroke hemiparesis.
      Further studies should be conducted to validate the use of GVI in the post-stroke
      population.

PMID- 30220717
TI  - Influence of body posture on foot load distribution in young school-age children.
AB  - : Young school-age children are particularly prone to postural defects because
      they are in a period of development of the spine that is exposed to a number of
      factors impairing its normal growth. A change in the shape of the spinal column
      causes a shift in the centre of gravity. Therefore, this study attempted to
      assess the influence of body posture on distribution of the load transferred by
      the lower limbs. METHODS: For each of the examined children, this study
      determined the parameters describing the body posture with the use of the
      photogrammetric method and the parameters describing plantar force distribution.
      The statistical analyses were performed using the U Mann- Whitney test and the
      student's t-test. The correlations between the parameters of the body posture and
      the parameters describing the foot load distribution were analysed using the
      Pearson correlation coefficient. These analyses were performed at a statistically
      significant level of p < 0.05. RESULTS: The tests conducted showed an occurrence
      of postural defects in about 42% of the subjects and excessively uneven loading
      of the lower limbs in about 65% of the children. CONCLUSIONS: The authors
      obtained a medium intensity correlation between the analysed parameters for the
      groups of boys and girls.

PMID- 30220718
TI  - Leg strength and power in Polish striker soccer players.
AB  - PURPOSE: The main goal of the present study was to examine muscle strength and
      power of dominant and non-dominant leg, knee extensors and flexors, and their
      correlations with jumping performances in soccer players. A secondary aim was to
      evaluate muscle sense. METHODS: 31 male professional strikers (age 20.9 +/- 2.3
      years, body mass 75.1 +/- 6.6 kg, body height 179.5 +/- 4.7 cm) participated in
      the study. The power output of lower extremities and the height of rise of the
      body mass centre during vertical jumps were measured using a force plate. The
      maximum muscle torque of the flexors and extensors of the knee were measured
      under isometric conditions using a special isometric torquemeter. Force sense was
      measured in isometric conditions in two tests: (a) fifty percent of the maximal
      voluntary contraction was set as a value of target force and the participants
      were instructed to reproduce the target force, (b) the participants attempted to
      develop a torque reproducing a sine course within the range of 10 to 50% of MVC
      performed. RESULTS: A direct relationship was observed between the peak muscle
      torque in knee extensors developed during isokinetic contraction at all
      velocities and power and height of three types of vertical jumps ( p <0.05). No
      correlation was observed between jumping performance and muscle torque under
      isometric condition. No differences were found in strength and jumping abilities
      as well as in force sense between dominant and non-dominant legs. CONCLUSIONS:
      This study offered a comprehensive and complete evaluation of leg muscle
      strength, sense and power, with the use of using force plate and isokinetic
      dynamometry.

PMID- 30220719
TI  - Evaluation of relationship between the results of selected tests for muscle
      strength assessment of the hip abductors.
AB  - PURPOSE: The assessment of hip joint abductor muscle strength is most often
      carried out using a dynamometric test. However, both in clinical practice and
      literature, evaluation is performed by means of the single-leg half-squat or the
      amount of abduction movements performed in the hip joint. In this context, the
      question arises whether the results of individual tests are convergent. The aim
      of the study is to evaluate the relationship between strength of the hip abductor
      muscle measured by dynamometer, the single-leg-squat and the number of
      repetitions of the movements in time. METHODS: A group of 35 students (20 women
      and 15 men) between 20 and 24 years old participated in the study. Each student
      was subjected to three tests assessing the condition of the hip and associated
      abductor muscles. Those included: assessment of hip joint abduction muscle
      strength in a dynamometric study, assessment of the number of abdomen movements
      performed lying on the side and standing, during a 30-second interval, and the
      single-leg-squat test. RESULTS: Based on the tests conducted, a significant
      relationship was observed between the muscle strength measurement results for the
      left and right side in the dynamometric study and the number of hip abduction
      repetitions in 30 seconds and the single-leg-squat test. CONCLUSIONS: The
      obtained results indicate a significant relationship between the results of all
      the tests. In practice, this means that the tests can be used interchangeably.

PMID- 30220720
TI  - Comparison of different suture techniques for Achilles tendon repair in rat model
      using collagen scaffolds.
AB  - PURPOSE: Tendon injury is an increasing problem in orthopedic and trauma surgery
      due to aging of the population and increased activity demands. Many rodent animal
      models are used in order to evaluate tendon reconstruction. Although tendon
      reruptures are a well- -known clinical problem, the outcomes of tendon repair in
      animal models are rarely discussed in the literature. The goal of the present
      experimental study was to compare the primary fixation stability of three suture
      techniques for repair of Achilles tendon defects in a rat model using a collagen
      scaffold. METHODS: Cadaveric left hind limbs of Sprague-Dawley rats were prepared
      with an Achilles tendon defect of 3 mm and rejoined using a collagen scaffold.
      Three suture configurations (simple, simple stitch with additional framing
      suture, and modified Mason-Allen stitch; n = 5 each) underwent tensile testing
      until complete failure was observed. RESULTS: Under a load of a mean value of 6.6
      N, the failure load of simple stitches was the significantly lowest ( p < 0.01).
      Both, modified Mason-Allen stitches and simple stitches with additional framing
      suture showed a mean failure load of more than 14 N. Regardless of the suture
      technique, most of the samples showed failure of tendon due to suture tear-out.
      The suture material as well as the scaffold remained mostly intact. CONCLUSIONS:
      Although simple end-to-end suture techniques are common in the literature,
      stitches with more suture strands should be preferred. Using techniques like an
      additional framing suture or modified Mason-Allen stitch, maximum failure load
      can be doubled and the risk of tendon rerupture may be decreased within in vivo
      testing.

PMID- 30220721
TI  - The influence of gender, dominant lower limb and type of target on the velocity
      of taekwon-do front kick.
AB  - PURPOSE: The current study aimed to quantify the main influences and the
      interactions (joint effects) of gender, leg and type of target on the
      biomechanics of front kick quality. Through the quantification, we tried to
      identify the relevant factors related to the kick accuracy and maximum velocity
      for coaching practice. METHODS: A ten-camera NIR VICON MX40 motion capture system
      (250 Hz) was used to determine the kicking foot maximum velocity from two well
      trained subject groups (8 males and 6 females). Each subject performed both left
      and right front kicks in a lateral standing position into the air (without a
      physical target), to a board, to a table tennis ball and to a training shield.
      The target were set on a height corresponding to a height of solar plexus of each
      participant. RESULTS: The results showed that all the three factors (gender, leg
      and type of target) have significant influences on kicking speed ( p < 0.001) and
      significant interaction (joint effect) was only found between gender and target (
      p < 0.001). Further analysis revealed that the males' kicking maximum velocity
      was affected more by board, while females' one was affected by the size of the
      target. CONCLUSIONS: The results would seem to suggest that, for males, kick-to-a
      board may be the more effective method for increasing kick quality, compared to
      other type of target. For females, kick-to-a-small-ball appears to be effective
      method for increasing kick maximum velocity.

PMID- 30220722
TI  - The assessment of the relationships between body posture indices and the Y
      Balance Test results in the adolescents.
AB  - PURPOSE: The purpose of this work was to assess the differences of the values of
      body posture indices, measured with the Moire's method, between girls and boys
      aged 13 and the relationships of these values with the results of the Y-Balance
      Test. METHODS: The study involved a group of healthy volunteers attending junior
      high schools in Cracow. The group consisted of 20 girls and 35 boys. Basic
      somatic parameters were measured within this work: body height and weight. Body
      posture was assessed according to the general methodology of the Moire's
      technique and 14 body posture indices were obtained as a result: 6 in the
      sagittal plane, 1 in the axial plane and 7 in the coronal plane. Postural
      stability was assessed with the Y-Balance Test (YBT). RESULTS: The studied girls
      and boys had practically the same body posture - statistical differences were
      found only in 3 out of 14 assessed indices measured with the Moire's technique.
      Scoliosis was found in as many as 51% of the subjects, however, mean values of
      deviations from the C7-S1 line were not large. CONCLUSIONS: In the group of
      girls, the set of blades (below - above) was statistically significantly
      correlated with the global YBT result for the right inferior extremity, and in
      the group of boys - the set of the waist triangles (below - above) was
      statistically significantly correlated with the global YBT results for the right
      and left inferior extremities.

PMID- 30220723
TI  - Pullout evaluation of sawbone experiment in different types of pedicle screws
      combined with bone cement augmentation for severe osteoporotic spine.
AB  - PURPOSE: The conventional screw is unable to provide enough screw-bone interface
      strength for osteoporotic cencellous bone, and complications resulting from
      loosening or failure of the implants remain a significant clinical problem.
      Hence, the purpose of this study is to investigate pullout strength and energy in
      three types of the pedicle screws, including conventional solid pedicle screw,
      cannulated pedicle screw, and cannulated pedicle screw with a central pin, using
      osteoporotic sawbone test block with different bone cement volumes through
      pullout force testing. METHODS: The control group (n = 15) of the osteoporotic
      sawbone test block includes groups A, B, and C to reflect three types of the
      pedicle screws without bone cement augmentation. The cemented group (n = 45) of
      the osteoporotic sawbone test block includes groups D1, D2, D3, E1, E2, E3, F1,
      F2, and F3 to reflect three types of the pedicle screws with PMMA bone cement of
      2, 3, and 4 mL augmentation. RESULTS: The results showed that the pullout
      strength and energy in the cemented group were significantly larger than that in
      the control group. Moreover, the best performances of the pullout strength and
      energy in the cemented group were evidenced obviously in the case of cannulated
      pedicle screw with a central pin with 4 mL bone cement augmentation. CONCLUSIONS:
      This study concludes that cement argumentation in the cannulated pedicle screw
      with a central pin can increase a pullout strength of pedicle screw for severe
      osteoporotic patients while bone cement of injective volume is limited.

PMID- 30220724
TI  - Surface analysis of long-term hemodialysis catheters made of carbothane
      (poly(carbonate)urethane) before and after implantation in the patients' bodies.
AB  - PURPOSE: The vascular cannulation is associated with a number of complications.
      The aim of this work was to study the composition and distribution of the film
      covering the surfaces of Mahurkar Maxid and Palindrome catheters, which were
      removed from the body of long-term hemodialysis patients. Moreover, the roughness
      and contact angle of the catheters were evaluated. METHODS: Two brand new (as a
      reference) and thirty used catheters were the subject of the study. Their
      implantation period lasted from 4 months to a year and the reason for removal was
      the production of another vascular access or obstruction. Surfaces were analyzed
      by scanning electron microscope, atomic force microscope and goniometer. RESULTS:
      The inner surfaces of the used catheters were covered with a film of various
      complexity which includes a plurality of protein, blood cell counts and the
      crystals. The closer to the distal part the film becomes more complex and multi
      layered. Even the surfaces of brand new catheter were not completely smooth. The
      only significant difference between analyzed models was the presence of thrombus
      in the distal part of Mahurkar Maxid catheters, not in the Palindrome.
      CONCLUSIONS: The distal part of the catheters is the place most exposed to
      obstruction and infection, which may be due to not reaching the anticoagulant
      agent into this part. Not only the occurrence of side holes affects the formation
      of thrombus, but also their quantity, geometry and distribution which effect on
      fluid mechanics. The surface of the catheters needs to improvement to minimize
      the occurrence of defects and cracks.

PMID- 30220725
TI  - How foot morphology changes influence shoe comfort and plantar pressure before
      and after long distance running?
AB  - PURPOSE: Prolonged running has been popularized globally in recent decades. This
      study was aimed to reveal information about foot morphology, shoe comfort and
      plantar loading among recreational heel-strike runners. METHODS: Twenty-six
      runners participated in foot morphology, perceived scores and peak pressure tests
      after 10- and 20-km track running. The foot morphology was measured using a 3D
      foot scanner, perceived scores were recorded using a visual analogue scale and
      plantar pressure was measured via insole plantar pressure measurement system. The
      statistical significance level was set at 0.05. RESULTS: The heel midsole
      materials properties were measured before and after 20 km. Significant changes
      were observed in ball width and girth, arch height and foot volume. The perceived
      scores showed significance in overall, forefoot and heel comfort, arch support
      and forefoot width. Peak pressure to the heel, medial mid-foot and metatarsal
      greatly increased. The first metatarsal showed consecutive increase from static
      to 10 km, and 20 km, while big-toe showed a decrease. CONCLUSIONS: The morphology
      variations and forefoot loading concentration may lead to discomfort and possibly
      imply dermatological problems and metatarsal bone stress, particularly on the
      first metatarsal. Combining changes of heel midsole property, knowledge of foot
      shape, shoe perception and plantar pressure is of great value for recreational
      long-distance running shoes design and materials selection.

PMID- 30220726
TI  - Effect of different balance training programs on postural control in chronic
      ankle instability: a randomized controlled trial.
AB  - BACKGROUND: Chronic ankle instability (CAI) is a common sequence of ankle sprain.
      Conservative treatment of CAI is currently accepted as a primary mean of managing
      the condition and preventing of recurrence. OBJECTIVES: The purpose of the
      current study was to evaluate the effect of Weight-bearing Exercise for Better
      Balance (WEBB) program and unilateral balance training exercises on postural
      control in females with CAI. METHODS: Thirty-five females with CAI participated
      in this study. The participants' mean values of age, body mass, height, and body
      mass index were 21.76 +/- 1.96 y, 64.82 +/- 9.37 kg, 161.85 +/- 7.24 cm, and
      24.76 +/- 3.76 kg/m2, respectively. They were randomly assigned into three
      groups: experimental group A (n = 13) who received WEBB program, experimental
      group B (n = 12) who received unilateral balance training, and control group C (n
      = 10) using statistical random tables. Balance parameters were measured for all
      participants via Biodex Balance System (BBS) before and after four weeks of
      balance training. They included overall stability index (OASI), antero-posterior
      stability index (APSI), and medio-lateral stability index (MLSI). RESULTS: There
      was a significant improvement in the post testing mean values of OASI and APSI,
      compared with the pre testing values in both experimental groups (A and B). There
      was no significant difference between the pre and post testing mean values of
      MLSI in the experimental group (A). CONCLUSIONS: Both WEBB program and unilateral
      balance training have positive effects on postural control in females with CAI.

PMID- 30220727
TI  - One step 3D printing of surface functionalized composite scaffolds for tissue
      engineering applications.
AB  - : their surface properties. A main challenge in this area is the development of
      processing routes enabling for a simple but efficient surface design of complex
      shaped geometries. Against this background, this work aimed at the implementation
      of self-assembly principles for surface functionalization of 3D-printed
      poly(lactic-co-glycolic acid) (PLGA)-based constructs with macro- and microporous
      geometries via precision extruding deposition. METHODS: Three-component melts
      from PLGA, CaCO3 and amphiphilic polymers (poly(2-oxazoline) block copolymer)
      were printed and their bulk and surface properties were studied. RESULTS: Melts
      with up to 30 mass % of CaCO3 could be successfully printed with homogeneously
      distributed mineral particles. PLGA degradation during the printing process was
      temperature and time dependent: the molecular weight reached 10 to 15% of the
      initial values after ca. 120 min of heat exposure. Filament surfaces from melts
      containing CaCO3 show an increasing microroughness along with increasing CaCO3
      content. Surface roughness and amphiphilic polymer content improve scaffold
      wettability with both factors showing synergistic effects. The CaCO3 content of
      the melts affected the inner filament structure during in vitro degradation in
      PBS, resulting in a homogeneous mineral particle-associated microporosity for
      mineral contents of 20 mass % and above. CONCLUSIONS: These results provide novel
      insights into the behavior of three-component melts from PLGA, CaCO3 and
      amphiphilic polymers during precision extruding deposition and show for the first
      time that self-assembly processes can be used to tailor scaffolds surface
      properties under such processing conditions.

PMID- 30220728
TI  - Automated motion-artifact correction in an OCTA image using tensor voting
      approach.
AB  - Optical coherence tomography angiography (OCTA) is a promising tool for imaging
      subsurface microvascular networks owing to its micron-level resolution and high
      sensitivity. However, it is not uncommon that OCTA imaging suffers from strip
      artifacts induced by tissue motion. Although various algorithms for motion
      correction have been reported, a method that enables motion correction on a
      single en face OCTA image remains a challenge. In this study, we propose a motion
      correction approach based on microvasculature detection and broken gap filling.
      Unlike previous methods using registration to restore disturbed vasculature
      during motion artifact removal, tensor voting is performed in an individual
      projected image to connect the broken vasculature. Both simulation and in vivo 3D
      OCTA imaging of the mouse bladder are performed to validate the effectiveness of
      this method. A comparison of in vivo images before and after motion correction
      shows that our method effectively corrects tissue motion artifacts while
      preserving the continuity of vasculature network. Furthermore, in vivo results of
      this technique are presented to demonstrate its utility for imaging tumor
      angiogenesis in the mouse bladder.

PMID- 30220730
TI  - Discourses of Mass Probation: From Managing Risk to Ending Human Warehousing in
      Michigan.
AB  - Over the past decade, some Western countries have begun to re-embrace the
      language of rehabilitation and calls for penal moderation. Risk logics-which
      undergirded the rise of mass incarceration in the U.S.-are now being repurposed
      to call for decarceration. Yet while risk played a key role in the transformation
      from modern to post-modern punishment, its development remains poorly understood.
      This article explores the discourses and practices of risk from the 1970s through
      to 2014 in one U.S. state (Michigan). The analyses focus on probation, the
      primary alternative to prison. The results show that risk discourses and
      practices emerged in the 1970s as a mode of resistance to the prison boom and
      have been adapted in each subsequent decade to address state governing crises.

PMID- 30220731
TI  - Kinetics and Characterization of Degradation Products of Dihydralazine and
      Hydrochlorothiazide in Binary Mixture by HPLC-UV, LC-DAD and LC-MS Methods.
AB  - Dihydralazine and hydrochlorothiazide were stored at high temperature and
      humidity, under UV/Vis light and different pH, as individual drugs and the
      mixture. Then, a sensitive and selective HPLC-UV method was developed for
      simultaneous determination of dihydralazine and hydrochlorothiazide in presence
      of their degradation products. Finally, the degradation products were
      characterized through LC-DAD and LC-MS methods. Dihydralazine was sensitive to
      high temperature and humidity, UV/Vis light and pH >= 7. At the same time, it was
      resistant to acidic conditions. Hydrochlorothiazide was sensitive to high
      temperature and humidity, UV/Vis light and changes in pH. Its highest level of
      degradation was observed in 1 M HCl. Degradation of the drugs was higher when
      they were stressed in the mixture. In the case of dihydralazine, the percentage
      degradation was 5-15 times higher. What is more, dihydralazine became sensitive
      to acidic conditions. Hydrochlorothiazide was shown to be more sensitive to
      UV/Vis light and pH > 4. Degradation of dihydralazine and hydrochlorothiazide
      followed first-order kinetics. The quickest degradation of dihydralazine was
      found to be in 1 M NaOH while of hydrochlorothiazide was in 1 M HCl (individual
      hydrochlorothiazide) or at pH 7-10 (hydrochlorothiazide in the mixture). A number
      of new degradation products were detected and some of them were identified by our
      LC-DAD and LC-MS methods. In the stressed individual samples,
      (phenylmethyl)hydrazine and 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide were
      observed for the first time. Interactions between dihydralazine and
      hydrochlorothiazide in the mixture were confirmed by additional degradation
      products, e.g., 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1,4-trioxide.

PMID- 30220732
TI  - Impact of Ionic Strength of Carrier Liquid on Recovery in Flow Field-Flow
      Fractionation.
AB  - Asymmetrical flow field-flow fractionation (AF4) and hollow-fiber flow field-flow
      fractionation (HF5) are techniques widely used in analytical, industrial and
      biological analyses. The main problem in all AF4 and HF5 analyses is sample loss
      due to analyte-membrane interactions. In this work the impact of liquid carrier
      composition on latex nanoparticles (NPs) separation in water and two different
      concentrations of NH4NO3 was studied. In AF4, a constant trend of decreasing the
      size of 60 and 121.9 nm particles induced by the ionic strength of the carrier
      liquid has been observed. In contrast, an agglomeration effect of the biggest 356
      nm particles was observed when increasing ionic strength, which induced a
      significant drop of recovery to 35%. H5F provides better resolution and
      intensified peaks of NPs, but careful optimisation of system parameters is
      mandatory to obtain good separation.

PMID- 30220733
TI  - Cross-scale interactions affect tree growth and intrinsic water use efficiency
      and highlight the importance of spatial context in managing forests under global
      change.
AB  - 1. We investigated the potential of cross-scale interactions to affect the
      outcome of density reduction in a large-scale silvicultural experiment to better
      understand options for managing forests under climate change. 2. We measured tree
      growth and intrinsic water-use efficiency (iWUE) based on stable carbon isotopes
      delta13C) to investigate impacts of density reduction across a range of
      progressively finer spatial scales: site, stand, hillslope position, and
      neighborhood. In particular, we focused on the influence of treatments beyond the
      boundaries of treated stands to include impacts on downslope and neighboring
      stands across sites varying in soil moisture. 3. Trees at the wet site responded
      with increased growth when compared with trees at the dry site. Additionally,
      trees in treated stands at the dry site responded with increased iWUE while trees
      at the wet site showed no difference in iWUE compared to untreated stands. 4. We
      hypothesized that water is not the primary limiting factor for growth at our
      sites, but that density reduction released other resources, such as growing space
      or nutrients to drive the growth response. At progressively finer spatial scales
      we found that tree responses were not driven by hillslope location (i.e.,
      downslope of treatment) but to changes in local neighborhood tree density. 5.
      Synthesis. This study demonstrated that water can be viewed as an agent to
      investigate cross-scale interactions as it links processes operating at coarse to
      finer spatial scales and vice versa. Consequently, management prescriptions such
      as density reductions to increase resistance and resilience of trees to climate
      change, specifically to drought, need to consider cross-scale interactions as
      specific magnitude and mechanisms of growth responses can only be predicted when
      multiple scales are taken into account.

PMID- 30220729
TI  - Combining community resurvey data to advance global change research.
AB  - More and more ecologists have started to resurvey communities sampled in earlier
      decades to determine long-term shifts in community composition and infer the
      likely drivers of the ecological changes observed. However, to assess the
      relative importance of, and interactions among, multiple drivers joint analyses
      of resurvey data from many regions spanning large environmental gradients are
      needed. In this paper we illustrate how combining resurvey data from multiple
      regions can increase the likelihood of driver-orthogonality within the design and
      show that repeatedly surveying across multiple regions provides higher
      representativeness and comprehensiveness, allowing us to answer more completely a
      broader range of questions. We provide general guidelines to aid implementation
      of multi-region resurvey databases. In so doing, we aim to encourage resurvey
      database development across other community types and biomes to advance global
      environmental change research.

PMID- 30220734
TI  - Mothers' and Fathers' Well-Being in Parenting Across the Arch of Child
      Development.
AB  - Limited research on parental well-being by child age suggests that parents are
      better off with very young children, despite intense time demands of caring for
      them. This study uses the American Time Use Survey Well-Being Module (N = 18,124)
      to assess how parents feel in activities with children of different ages. Results
      show that parents are worse off with adolescent children relative to young
      children. Parents report the lowest levels of happiness with adolescents relative
      to younger children, and mothers report more stress and less meaning with
      adolescents. Controlling for contextual features of parenting including activity
      type, solo parenting, and restorative time does not fully account for the
      adolescent disadvantage in fathers' happiness or mothers' stress. This study
      highlights adolescence as a particularly difficult stage for parental well-being,
      and it shows that mothers shoulder stress that fathers do not, even after
      accounting for differences in the context of their parenting activities.

PMID- 30220735
TI  - Quantifying individual specialization using tracking data: a case study on two
      species of albatrosses.
AB  - Many predictive models of spatial and temporal distribution (e.g. in response to
      climate change or species introductions) assume that species have one
      environmental niche that applies to all individuals. However, there is growing
      evidence that individuals can have environmental preferences that are narrower
      than the species niche. Such individual specialization has mainly been studied in
      terms of dietary niches, but a recent increase in the availability of individual
      movement data opens the possibility of extending these analyses to specialisation
      in environmental preferences. Yet, no study to date on individual specialisation
      has considered the environmental niche in its multidimensionality. Here we
      propose a new method for quantifying individual specialisation in multiple
      dimensions simultaneously. We compare the hypervolumes in n-dimensional
      environmental niche space of each individual against that of the population,
      testing for significant differences against a null model. The same method can be
      applied to a 2-dimensional geographic space to test for site fidelity. We applied
      this method to test for individual environmental specialisation (across three
      dimensions: sea surface temperature, eddy kinetic energy, depth) and for site
      fidelity among satellite-tracked black-browed albatrosses (Thalassarche
      melanophris) and grey-headed albatrosses (Thalassarche chrysostoma), during chick
      rearing at South Georgia. We found evidence for site fidelity in both species and
      of environmental specialisation among individual grey-headed but not black-browed
      albatrosses. Specialisation can affect the resilience of populations affected by
      natural and anthropogenic changes in the environment, and hence has implications
      for population dynamics and conservation.

PMID- 30220736
TI  - Differences in the respiratory response to temperature and hypoxia across four
      life-stages of the intertidal porcelain crab Petrolisthes laevigatus.
AB  - For aquatic breathers, hypoxia and warming can act synergistically causing a
      mismatch between oxygen supply (reduced by hypoxia) and oxygen demand (increased
      by warming). The vulnerability of these species to such interactive effects may
      differ during ontogeny due to differing gas exchange systems. This study examines
      respiratory responses to temperature and hypoxia across four life-stages of the
      intertidal porcelain crab Petrolisthes laevigatus. Eggs, megalopae, juveniles and
      adults were exposed to combinations of temperatures from 6 to 18  degrees C and
      oxygen tensions from 2 to 21 kPa. Metabolic rates differed strongly across life
      stages which could be partly attributed to differences in body mass. However,
      eggs exhibited significantly lower metabolic rates than predicted for their body
      mass. For the other three stages, metabolic rates scaled with a mass exponent of
      0.89. Mass scaling exponents were similar across all temperatures, but were
      significantly influenced by oxygen tension (the highest at 9 and 14 kPa, and the
      lowest at 2 kPa). Respiratory responses across gradients of oxygen tension were
      used to calculate the response to hypoxia, whereby eggs, megalopae and juveniles
      responded as oxyconformers and adults as oxyregulators. The thermal sensitivity
      of the metabolic rates (Q10) were dependent on the oxygen tension in megalopae,
      and also on the interaction between oxygen tension and temperature intervals in
      adults. Our results thus provide evidence on how the oxygen tension can modulate
      the mass dependence of metabolic rates and demonstrate changes in respiratory
      control from eggs to adults. In light of our results indicating that adults show
      a good capacity for maintaining metabolism independent of oxygen tension, our
      study highlights the importance of assessing responses to multiple stressors
      across different life-stages to determine how vulnerability to warming and
      hypoxia changes during development.

PMID- 30220737
TI  - Toward a mechanistic understanding of trophic structure: inferences from
      simulating stable isotope ratios.
AB  - Stable isotope ratios (SIR) are widely used to estimate food-web trophic levels
      (TLs). We built systems dynamic N-biomass-based models of different levels of
      complexity, containing explicit descriptions of isotope fractionation and of
      trophic level. The values of delta15N and TLs, as independent and emergent
      properties, were used to test the potential for the SIR of nutrients, primary
      producers, consumers, and detritus to align with food-web TLs. Our analysis shows
      that there is no universal relationship between TL and delta15N that permits a
      robust prognostic tool for configuration of food webs even if all system
      components can be reliably analysed. The predictive capability is confounded by
      prior dietary preference, intra-guild predation and recycling of biomass through
      detritus. These matters affect the dynamics of both the TLs and SIR. While SIR
      data alone have poor explanatory power, they would be valuable for validating the
      construction and functioning of dynamic models. This requires construction of
      coupled system dynamic models that describe bulk elemental distribution with an
      explicit description of isotope discriminations within and amongst functional
      groups and nutrient pools, as used here. Only adequately configured models would
      be able to explain both the bulk elemental distributions and the SIR data. Such
      an approach would provide a powerful test of the whole model, integrating
      changing abiotic and biotic events across time and space.

PMID- 30220738
TI  - Convergence and adaptive discretization of the IRGNM Tikhonov and the IRGNM
      Ivanov method under a tangential cone condition in Banach space.
AB  - In this paper we consider the iteratively regularized Gauss-Newton method (IRGNM)
      in its classical Tikhonov version as well as two further-Ivanov type and Morozov
      type-versions. In these two alternative versions, regularization is achieved by
      imposing bounds on the solution or by minimizing some regularization functional
      under a constraint on the data misfit, respectively. We do so in a general Banach
      space setting and under a tangential cone condition, while convergence (without
      source conditions, thus without rates) has so far only been proven under stronger
      restrictions on the nonlinearity of the operator and/or on the spaces. Moreover,
      we provide a convergence result for the discretized problem with an appropriate
      control on the error and show how to provide the required error bounds by goal
      oriented weighted dual residual estimators. The results are illustrated for an
      inverse source problem for a nonlinear elliptic boundary value problem, for the
      cases of a measure valued and of an Linfinity source. For the latter, we also
      provide numerical results with the Ivanov type IRGNM.

PMID- 30220739
TI  - Circulant embedding with QMC: analysis for elliptic PDE with lognormal
      coefficients.
AB  - In a previous paper (Graham et al. in J Comput Phys 230:3668-3694, 2011), the
      authors proposed a new practical method for computing expected values of
      functionals of solutions for certain classes of elliptic partial differential
      equations with random coefficients. This method was based on combining quasi
      Monte Carlo (QMC) methods for computing the expected values with circulant
      embedding methods for sampling the random field on a regular grid. It was found
      capable of handling fluid flow problems in random heterogeneous media with high
      stochastic dimension, but no convergence theory was provided. This paper provides
      a convergence analysis for the method in the case when the QMC method is a
      specially designed randomly shifted lattice rule. The convergence result depends
      on the eigenvalues of the underlying nested block circulant matrix and can be
      independent of the number of stochastic variables under certain assumptions. In
      fact the QMC analysis applies to general factorisations of the covariance matrix
      to sample the random field. The error analysis for the underlying fully discrete
      finite element method allows for locally refined meshes (via interpolation from a
      regular sampling grid of the random field). Numerical results on a non-regular
      domain with corner singularities in two spatial dimensions and on a regular
      domain in three spatial dimensions are included.

PMID- 30220740
TI  - The Collection 6 MODIS burned area mapping algorithm and product.
AB  - The two Moderate Resolution Imaging Spectroradiometer (MODIS) instruments on
      board NASA's Terra and Aqua satellites have provided nearly two decades of global
      fire data. Here, we describe refinements made to the 500-m global burned area
      mapping algorithm that were implemented in late 2016 as part of the MODIS
      Collection 6 (C6) land-product reprocessing. The updated algorithm improves upon
      the heritage Collection 5.1 (C5.1) MCD64A1 and MCD45A1 algorithms by offering
      significantly better detection of small burns, a modest reduction in burn-date
      temporal uncertainty, and a large reduction in the extent of unmapped areas.
      Comparison of the C6 and C5.1 MCD64A1 products for fifteen years (2002-2016) on a
      regional basis shows that the C6 product detects considerably more burned area
      globally (26%) and in almost every region considered. The sole exception was in
      Boreal North America, where the mean annual area burned was 6% lower for C6,
      primarily as a result of a large increase in the number of small lakes mapped
      (and subsequently masked) at high latitudes in the upstream C6 input data. With
      respect to temporal reporting accuracy, 44% of the C6 MCD64A1 burned grid cells
      were de-tected on the same day as an active fire, and 68% within 2 days, which
      represents a substantial reduction in temporal uncertainty compared to the C5.1
      MCD64A1 and MCD45A1 products. In addition, an areal accuracy assessment of the C6
      burned area product undertaken using high resolution burned area reference maps
      derived from 108 Landsat image pairs is reported.

PMID- 30220741
TI  - The Long Road to Equality: A Meta-Regression Analysis of Changes in the Black
      Test Score Gap over Time.
AB  - Objective: We analyze changes in test score gaps between Black students and their
      peers from 1979 to 2010 and examine how observable factors contribute to the gap.
      Methods: Using meta-regression, we examine the relationship between African
      American racial status and achievement in United States K-12 education in 165
      published studies. Results: The absolute relationship between Black status and
      achievement decreased during the 1980s and early 1990s, but was stagnant from the
      late 1990s through 2010. Socioeconomic status explained more than half of the
      gap, and the influence of socioeconomic status on the gap did not changed
      significantly over time. Schooling characteristics explained relatively little of
      the gap, but school-level factors increased in importance over time. Conclusions:
      Black test score gap closure stagnated in an era when federal education policy
      sought to close racial achievement gaps. Observable factors explain more of the
      gap than has been previously recognized.

PMID- 30220742
TI  - Race/Ethnic Differences in Nonresident Fathers' Involvement after a Nonmarital
      Birth.
AB  - Objectives: This article examines how the levels of nonresidential father
      involvement (over child ages 1 to 9) differ by race/ethnicity (comparing White,
      Black and Hispanic fathers), and then considers how individual and couple
      characteristics may 'account for' any observed differences. Method: Data from the
      Fragile Families and Child Wellbeing Study (N = 2,447) and random effects models
      were used to examine how nonresidential father involvement (with respect to time,
      engagement, shared responsibility, and coparenting with mothers) is
      differentiated by race and ethnicity. Results: Overall, Black nonresident fathers
      were significantly more likely to spend time and engage in activities with their
      children as compared to Hispanic fathers-but not White fathers. Black fathers
      also shared responsibilities more frequently and displayed more effective
      coparenting than Hispanic and White fathers. Conclusions: Fathers' involvement
      with children is shown to differ across major race/ethnic groups, with
      implications for children as well as for future research and public policy.

PMID- 30220743
TI  - Quantifying wear depth in hip prostheses using a 3D optical scanner.
AB  - The visualization of wear depth in hip prostheses can assist the evaluation of
      new bearing materials and implant designs. The goal of this study was to develop
      an accurate, fast, and economical methodology to generate colorimetric maps of
      wear depth in hip implants using a structured light 3D optical scanning system.
      The accuracy and precision of this novel technique were determined using
      reference blocks with known wear depths. This technique was then used to measure
      the in vitro wear of a hip resurfacing device for canines that incorporates a
      highly cross-linked polyethylene liner. The 3D optical scanner had an average
      accuracy of 2.1 um and an average precision of 1.4 um, which corresponded to
      errors less than 10% when measuring wear depths of 20 um or greater. The scanner
      was able to repeatedly generate 3D colorimetric maps of wear depth in highly
      cross-linked polyethylene liners in 20 min or less. These colorimetric maps
      identified localized regions with 3-fold greater wear than the average wear
      depth, and revealed liners with asymmetric wear patterns. For the first time,
      this study has validated the use of 3D optical scanning to quantify in vitro
      surface wear in a hip replacement device.

PMID- 30220744
TI  - What do self-reports of wellbeing say about life-cycle theory and policy?
AB  - I respond to Atkinson's plea to revive welfare economics, and to considering
      alternative ethical frameworks when making policy recommendations. I examine a
      measure of self-reported evaluative wellbeing, the Cantril Ladder, and use data
      from Gallup to examine wellbeing over the life-cycle. I assess the validity of
      the measure, and show that it is hard to reconcile with familiar theories of
      intertemporal choice. I find a worldwide optimism about the future; in spite of
      repeated evidence to the contrary, people consistently but irrationally predict
      they will be better off five years from now. The gap between future and current
      wellbeing diminishes with age, and in rich countries, is negative among the
      elderly. I also use the measure to think about income transfers by age and sex.
      Policies that give priority those with low incomes favor the young and the old,
      while utilitarian policies favor the middle aged, and men over women.

PMID- 30220745
TI  - A NEW PERSPECTIVE ON ROBUST M-ESTIMATION: FINITE SAMPLE THEORY AND APPLICATIONS
      TO DEPENDENCE-ADJUSTED MULTIPLE TESTING.
AB  - Heavy-tailed errors impair the accuracy of the least squares estimate, which can
      be spoiled by a single grossly outlying observation. As argued in the seminal
      work of Peter Huber in 1973 [Ann. Statist.1 (1973) 799-821], robust alternatives
      to the method of least squares are sorely needed. To achieve robustness against
      heavy-tailed sampling distributions, we revisit the Huber estimator from a new
      perspective by letting the tuning parameter involved diverge with the sample
      size. In this paper, we develop nonasymptotic concentration results for such an
      adaptive Huber estimator, namely, the Huber estimator with the tuning parameter
      adapted to sample size, dimension, and the variance of the noise. Specifically,
      we obtain a sub-Gaussian-type deviation inequality and a nonasymptotic Bahadur
      representation when noise variables only have finite second moments. The
      nonasymptotic results further yield two conventional normal approximation results
      that are of independent interest, the Berry-Esseen inequality and Cramer-type
      moderate deviation. As an important application to large-scale simultaneous
      inference, we apply these robust normal approximation results to analyze a
      dependence-adjusted multiple testing procedure for moderately heavy-tailed data.
      It is shown that the robust dependence-adjusted procedure asymptotically controls
      the overall false discovery proportion at the nominal level under mild moment
      conditions. Thorough numerical results on both simulated and real datasets are
      also provided to back up our theory.

PMID- 30220746
TI  - Child and case influences on recidivism in a statewide dissemination of
      Multisystemic Therapy for juvenile offenders.
AB  - Multisystemic Therapy (MST) is an evidence-based treatment for high-risk youth
      and their families shown to reduce subsequent delinquent activity. This study
      investigated (1) re-arrest rates of a statewide MST dissemination; and (2) the
      relation of child, family, and case characteristics to re-arrest rates following
      receipt of MST. Analyses examined outcomes for 633 youth following referral to
      MST. Separate models examined predictors of general re-arrest of any type and of
      more serious misdemeanor or felony arrests. Sixty-five percent of youth
      experienced a new arrest of any type within 12-months of MST initiation; fewer
      (53%) experienced a misdemeanor or felony charge in that timeframe. Recipients
      who were younger, had an externalizing behavior disorder, and had a greater
      number and severity of pre-MST charges were more likely to recidivate. Findings
      highlight potential child and case factors that may account for variability in
      treatment effects when MST is implemented broadly within a system.

PMID- 30220747
TI  - Studying grant decision-making: a linguistic analysis of review reports.
AB  - Peer and panel review are the dominant forms of grant decision-making, despite
      its serious weaknesses as shown by many studies. This paper contributes to the
      understanding of the grant selection process through a linguistic analysis of the
      review reports. We reconstruct in that way several aspects of the evaluation and
      selection process: what dimensions of the proposal are discussed during the
      process and how, and what distinguishes between the successful and non-successful
      applications? We combine the linguistic findings with interviews with panel
      members and with bibliometric performance scores of applicants. The former gives
      the context, and the latter helps to interpret the linguistic findings. The
      analysis shows that the performance of the applicant and the content of the
      proposed study are assessed with the same categories, suggesting that the
      panelists actually do not make a difference between past performance and
      promising new research ideas. The analysis also suggests that the panels focus on
      rejecting the applications by searching for weak points, and not on finding the
      high-risk/high-gain groundbreaking ideas that may be in the proposal. This may
      easily result in sub-optimal selections, in low predictive validity, and in bias.

PMID- 30220749
TI  - Validation of a closing procedure for fourth-order RANS turbulence models with
      DNS data in an incompressible zero-pressure-gradient turbulent boundary layer.
AB  - Among factors affecting the accuracy of flow simulations with Reynolds-Averaged
      Navier-Stokes turbulence models is modeling turbulent diffusion processes. With
      the use of the Gram-Charlier series expansions, the turbulent diffusion in fourth
      order one-point statistical closures of the Reynolds-Averaged Navier-Stokes
      equations can be modeled without introducing unknown model coefficients and
      without assuming turbulence being Gaussian. Terms representing turbulent
      diffusion processes in transport equations for second- and third-order velocity
      correlations do not require any modeling in such closures. In this regard, fourth
      order closures are a more accurate alternative to lower-order closures where
      turbulent diffusion is modeled on semi-empirical or Gaussian turbulence
      assumptions. In the current paper, the accuracy of the closing procedure based on
      the Gram-Charlier series expansions is evaluated using data of direct numerical
      simulations in an incompressible zero-pressure-gradient turbulent boundary layer
      over a flat plate. One-point third-, fourth-, and fifth-order velocity moments
      were extracted for this purpose from the dataset collected by the Fluid Dynamics
      Group at the Universidad Politecnica de Madrid at two streamwise locations
      Retheta= 4101 and 5200 that correspond to channels and pipes at delta+= 1331 and
      1626. Results demonstrate that the truncated Gram-Charlier series expansions are
      an accurate approximation of the fifth-order velocity moments in the considered
      flow.

PMID- 30220748
TI  - Factors influencing the scientific performance of Momentum grant holders: an
      evaluation of the first 117 research groups.
AB  - The Momentum program launched in 2009 provides funding of up to 1 million Euro to
      establish new, independent research groups at Hungarian academic institutions.
      Here, our aim was to determine factors associated with the scientific output of
      these research groups. Publication data were downloaded from the Hungarian
      Scientific Work Archive (www.mtmt.hu), impact factor data were obtained from
      Thomson Reuters (jcr.incites.thomsonreuters.com), and journal ranks were
      extracted from the Scimago Journal Rank database (www.scimagojr.com).
      Investigated input features for each grant holder include gender, degree,
      targeted category, international mobility, international grants, number of
      publications, total number of citations, H-index, best publications, impact
      factors in the last 2 years, and assessment scores provided by the experts.
      Evaluated performance indicators include cumulative impact factor, number of D1
      publications, and number of first/last author D1 publications during the grant
      running time. Grant holders' publication output increased by 23 and 52% for life
      sciences and material sciences researchers. Scientific performance was
      independent from gender, degree, international grants, category applied for, and
      citations received for the best pre-grant publication. Those with international
      mobility had significantly lower scientific output (yearly impact factor, number
      of D1 publications, number of first/last author publications). Scores received
      from grant review experts were independent from later publication activity. The
      strongest correlations were observed between scientific output and total number
      of citations, H-index, and impact factor in the last 2 years pre-grant. In
      summary, group leaders with a dynamic publication track record were able to
      attain the most additional momentum. Our results can help accelerate and improve
      future grant review processes.

PMID- 30220750
TI  - Women Who Love: An Explorative Study on Experiences of Lesbian and Bisexual Women
      with a Mild Intellectual Disability in The Netherlands.
AB  - Empirical research that addresses sexual orientation in people with an
      intellectual disability (ID) is limited, and very little is known regarding the
      personal experiences of lesbian and bisexual women with ID. This study set out to
      answer the question: What are the experiences of lesbian and bisexual women with
      a mild intellectual disability in the Netherlands? Ten lesbian and bisexual women
      (average age of 33 years) with a mild intellectual disability took part in our
      study comprising of semi-structured interviews. Participants reported that they
      had found it hard to talk to others about sensitive subjects such as their
      sexuality, and had been left to figure out information regarding their sexual
      orientation without support or guidance. Our results point to a lack of
      information, sexual education and role models when it comes to lesbian sex and
      women with an intellectual disability. Social contact was often limited, and
      participants experienced difficulties finding a partner. Furthermore,
      participants often had to cope with mental health problems and had struggled with
      loneliness, depression and addiction. Last but not least, our participants
      reported that they had been discriminated against. Coming out (revealing your
      sexual orientation) is not easy when you have an intellectual disability. To
      enable women with ID who have lesbian or bisexual feelings to understand and
      secure their sexual rights in their daily lives is important. Therefore, it is
      necessary to provide support in the following domains: sexual education and
      training, social contact and assertiveness.

PMID- 30220751
TI  - Conscientiousness and Effort-Related Cardiac Activity in Response to Piece-Rate
      Cash Incentives.
AB  - Although conscientiousness predicts many aspects of motivation, from delay of
      gratification to higher achievement, its relationship to responses to monetary
      incentives is surprisingly inconsistent. Several studies have found null or
      relationships between conscientiousness and behavioral performance in piece-rate,
      pay-for-performance tasks, in which people earn money for each unit of work
      completed. In the present study, we examined the role of conscientiousness in
      effort-related cardiac activity and behavioral performance during a pay-for
      performance task. People worked on a self-paced, piece-rate cognitive task in
      which they earned 1 cent or 5 cents, manipulated within-person, for each correct
      response. Conscientiousness predicted greater physiological effort (i.e., shorter
      pre-ejection period [PEP] reactivity) as incentives increased but had no effect
      on behavioral performance. The findings suggest that conscientiousness is
      significantly related to effort for piece-rate tasks, and they reinforce a core
      idea in motivational intensity theory: effort, performance, and persistence are
      distinct outcomes that often diverge, so drawing conclusions about effort from
      performance can be complex.

PMID- 30220752
TI  - Dynamic Measures of Anxiety-Related Threat Bias: Links to Stress Reactivity.
AB  - Exaggerated attention to threatening information, or the threat bias, has been
      implicated in the development and maintenance of anxiety disorders. Recent
      research has highlighted methodological limitations in threat bias measures, such
      as temporal insensitivity, leading to the development of novel metrics that
      capture change and variability in threat bias over time. These metrics, however,
      have rarely been examined in non-clinical samples. The present study aimed to
      explore the utility of these trial-level metrics in predicting anxiety-related
      stress reactivity (stress-induced negative mood state) in trait anxious adults (N
      = 52). Following a stressor, participants completed the dot probe task to
      generate threat bias scores. Stress reactivity was measured via stress-induced
      changes in subjective mood state. More variability in trial-level bias scores and
      greater bias away from threat (both mean and peak negative trial-level bias
      scores) predicted increased stress reactivity. The temporal characteristics of
      threat bias and implications for clinically-relevant measurement are discussed.

PMID- 30220753
TI  - Interactive effects of Traumatic Brain Injury and Anxiety Sensitivity Cognitive
      Concerns on Post-traumatic Stress among Active Duty Soldiers.

PMID- 30220754
TI  - Residuals and Diagnostics for Ordinal Regression Models: A Surrogate Approach.
AB  - Ordinal outcomes are common in scientific research and everyday practice, and we
      often rely on regression models to make inference. A long-standing problem with
      such regression analyses is the lack of effective diagnostic tools for validating
      model assumptions. The difficulty arises from the fact that an ordinal variable
      has discrete values that are labeled with, but not, numerical values. The values
      merely represent ordered categories. In this paper, we propose a surrogate
      approach to defining residuals for an ordinal outcome Y. The idea is to define a
      continuous variable S as a "surrogate" of Y and then obtain residuals based on S.
      For the general class of cumulative link regression models, we study the
      residual's theoretical and graphical properties. We show that the residual has
      null properties similar to those of the common residuals for continuous outcomes.
      Our numerical studies demonstrate that the residual has power to detect
      misspecification with respect to 1) mean structures; 2) link functions; 3)
      heteroscedasticity; 4) proportionality; and 5) mixed populations. The proposed
      residual also enables us to develop numeric measures for goodness-of-fit using
      classical distance notions. Our results suggest that compared to a previously
      defined residual, our residual can reveal deeper insights into model diagnostics.
      We stress that this work focuses on residual analysis, rather than hypothesis
      testing. The latter has limited utility as it only provides a single p-value,
      whereas our residual can reveal what components of the model are misspecified and
      advise how to make improvements.

PMID- 30220755
TI  - Statistical Challenges of Big Brain Network Data.
AB  - We explore the main characteristics of big brain network data that offer unique
      statistical challenges. The brain networks are biologically expected to be both
      sparse and hierarchical. Such unique characterizations put specific topological
      constraints onto statistical approaches and models we can use effectively. We
      explore the limitations of the current models used in the field and offer
      alternative approaches and explain new challenges.

PMID- 30220756
TI  - The role of trees in urban stormwater management.
AB  - Urban impervious surfaces convert precipitation to stormwater runoff, which
      causes water quality and quantity problems. While traditional stormwater
      management has relied on gray infrastructure such as piped conveyances to collect
      and convey stormwater to wastewater treatment facilities or into surface waters,
      cities are exploring green infrastructure to manage stormwater at its source.
      Decentralized green infrastructure leverages the capabilities of soil and
      vegetation to infiltrate, redistribute, and otherwise store stormwater volume,
      with the potential to realize ancillary environmental, social, and economic
      benefits. To date, green infrastructure science and practice have largely focused
      on infiltration-based technologies that include rain gardens, bioswales, and
      permeable pavements. However, a narrow focus on infiltration overlooks other
      losses from the hydrologic cycle, and we propose that arboriculture - the
      cultivation of trees and other woody plants - deserves additional consideration
      as a stormwater control measure. Trees interact with the urban hydrologic cycle
      by intercepting incoming precipitation, removing water from the soil via
      transpiration, enhancing infiltration, and bolstering the performance of other
      green infrastructure technologies. However, many of these interactions are
      inadequately understood, particularly at spatial and temporal scales relevant to
      stormwater management. As such, the reliable use of trees for stormwater control
      depends on improved understanding of how and to what extent trees interact with
      stormwater, and the context-specific consideration of optimal arboricultural
      practices and institutional frameworks to maximize the stormwater benefits trees
      can provide.

PMID- 30220757
TI  - Logical fallacies and invasion biology.
AB  - Leading invasion biologists sometimes dismiss critics and criticisms of their
      field by invoking "the straw man" fallacy. Critics of invasion biology are also
      labelled as a small group of "naysayers" or "contrarians", who are sometimes
      engaging in "science denialism". Such unfortunate labels can be seen as a way to
      possibly suppress legitimate debates and dismiss or minimize reasonable concerns
      about some aspects of invasion biology, including the uncertainties about the
      geographic origins and complex environmental impacts of species, and the control
      programs against species perceived as "invasive". In assessing the quality of the
      debate in this area, we examine the validity of the use of various strategies,
      including the "straw man" concept, and explore a range of potential logical
      fallacies present in some recent prominent discussions about invasion biology and
      so-called "invasive" species. The goal is to add some clarity to the concepts
      involved, point out some problematic issues, and improve the quality of the
      debates as the discussions move forward.

PMID- 30220758
TI  - Multiple crack detection in 3D using a stable XFEM and global optimization.
AB  - A numerical scheme is proposed for the detection of multiple cracks in three
      dimensional (3D) structures. The scheme is based on a variant of the extended
      finite element method (XFEM) and a hybrid optimizer solution. The proposed XFEM
      variant is particularly well-suited for the simulation of 3D fracture problems,
      and as such serves as an efficient solution to the so-called forward problem. A
      set of heuristic optimization algorithms are recombined into a multiscale
      optimization scheme. The introduced approach proves effective in tackling the
      complex inverse problem involved, where identification of multiple flaws is
      sought on the basis of sparse measurements collected near the structural
      boundary. The potential of the scheme is demonstrated through a set of numerical
      case studies of varying complexity.

PMID- 30220759
TI  - Patterns and predictors of childcare subsidies for children with and without
      special needs.
AB  - One goal of childcare subsidies is to increase access to quality childcare for
      families of low-income, thus supporting child and family wellbeing, but subsidies
      may not equally benefit children with and without special needs. This study
      examined patterns and predictors of subsidy use among children with disabilities
      or delays relative to children without special needs. A nationally representative
      sample of approximately 4,050 young children from families of low-income was
      drawn from the Early Childhood Longitudinal Study-Birth Cohort. We examined
      subsidized care receipt at ages nine months, two years, and four years using
      descriptive analyses and multivariate logistic regression. Results suggest young
      children with special needs utilize childcare subsidies at significantly lower
      rates than their peers without disabilities. Mothers' marital status, work
      status, education, and age, along with child's race and number of siblings were
      significant predictors of subsidy use. We discuss implications for policy
      implementation and multisector collaboration to support the early care and
      education of young children with special needs.

PMID- 30220760
TI  - RECOVERING A TREE FROM THE LENGTHS OF SUBTREES SPANNED BY A RANDOMLY CHOSEN
      SEQUENCE OF LEAVES.
AB  - Given an edge-weighted tree T with n leaves, sample the leaves uniformly at
      random without replacement and let Wk , 2 <= k <= n, be the length of the subtree
      spanned by the first k leaves. We consider the question, "Can T be identified (up
      to isomorphism) by the joint probability distribution of the random vector (W2,
      ..., Wn )?" We show that if T is known a priori to belong to one of various
      families of edge-weighted trees, then the answer is, "Yes." These families
      include the edge-weighted trees with edge-weights in general position, the
      ultrametric edge-weighted trees, and certain families with equal weights on all
      edges such as (k + 1)-valent and rooted k-ary trees for k >= 2 and caterpillars.

PMID- 30220761
TI  - In the light of change: a mixed methods investigation of climate perceptions and
      the instrumental record in northern Sweden.
AB  - Significant climate change in the Arctic has been observed by indigenous peoples
      and reported in scientific literature, but there has been little research
      comparing these two knowledge bases. In this study, Sami reindeer herder
      interviews and observational weather data were combined to provide a
      comprehensive description of climate changes in Northern Sweden. The interviewees
      described warmer winters, shorter snow seasons and cold periods, and increased
      temperature variability. Weather data supported three of these four observed
      changes; the only change not evident in the weather data was increased
      temperature variability. Winter temperatures increased, the number of days in
      cold periods was significantly reduced, and some stations displayed a 2 month
      shorter snow cover season. Interviewees reported that these changes to the
      wintertime climate are significant, impact their identity, and threaten their
      livelihood. If consistency between human observations of changing weather
      patterns and the instrumental meteorological record is observed elsewhere, mixed
      methods research like this study can produce a clearer, more societally relevant
      understanding of how the climate is changing and the impacts of those changes on
      human well-being.

PMID- 30220762
TI  - An approach to measure parameter sensitivity in watershed hydrological modelling.
AB  - Hydrological responses vary spatially and temporally according to watershed
      characteristics. In this study, the hydrological models that we developed earlier
      for the Little Miami River (LMR) and Las Vegas Wash (LVW) watersheds in the USA
      were used for detailed sensitivity analyses. To compare the relative
      sensitivities of the hydrological parameters of these two models, we used
      normalized root mean square error (NRMSE). By combining the NRMSE index with the
      flow duration curve analysis, we derived an approach to measure parameter
      sensitivities under different flow regimes. Results show that the parameters
      related to groundwater are highly sensitive in the LMR watershed, whereas the LVW
      watershed is primarily sensitive to near-surface and impervious parameters. The
      high and medium flows are more impacted by most of the parameters. The low flow
      regime was highly sensitive to groundwater-related parameters. Moreover, our
      approach is found to be useful in facilitating model development and calibration.

PMID- 30220763
TI  - Adolescent Brain and Cognitive Developments: Implications for Clinical Assessment
      in Traumatic Brain Injury.
AB  - Adolescence is a time of significant physical, social, and emotional
      developments, accompanied by changes in cognitive and language skills. Underlying
      these are significant developments in brain structures and functions including
      changes in cortical and subcortical gray matter and white matter tracts. Among
      the brain regions that develop during adolescence are areas that are commonly
      damaged as a result of a traumatic brain injury (TBI). This paper summarizes
      major brain changes during adolescence and evidence linking maturation of these
      cognitive and language functions to brain development, placing consideration of
      both areas of development in the context of rehabilitation for adolescents with
      TBI.

PMID- 30220764
TI  - Novel Analyses of Long-Term Data Provide a Scientific Basis for Chlorophyll-a
      Thresholds in San Francisco Bay.
AB  - San Francisco Bay (SFB), USA, is highly enriched in nitrogen and phosphorus, but
      has been resistant to the classic symptoms of eutrophication associated with over
      production of phytoplankton. Observations in recent years suggest that this
      resistance may be weakening, shown by: significant increases of chlorophyll-a
      (chl-a) and decreases of dissolved oxygen (DO), common occurrences of
      phytoplankton taxa that can form Harmful Algal Blooms (HAB), and algal toxins in
      water and mussels reaching levels of concern. As a result, managers now ask: what
      levels of chl-a in SFB constitute tipping points of phytoplankton biomass beyond
      which water quality will become degraded, requiring significant nutrient
      reductions to avoid impairments? We analyzed data for DO, phytoplankton species
      composition, chl-a, and algal toxins to derive quantitative relationships between
      three indicators (HAB abundance, toxin concentrations, DO) and chl-a. Quantile
      regressions relating HAB abundance and DO to chl-a were significant, indicating
      SFB is at increased risk of adverse HAB and low DO levels if chl-a continues to
      increase. Conditional probability analysis (CPA) showed chl-a of 13 mg m-3 as a
      "protective" threshold below which probabilities for exceeding alert levels for
      HAB abundance and toxins were reduced. This threshold was similar to chl-a of 13 
      16 mg m-3 that would meet a SFB-wide 80 % saturation Water Quality Criterion
      (WQC) for DO. Higher "at risk" chl-a thresholds from 25 - 40 mg m-3 corresponded
      to 0.5 probability of exceeding alert levels for HAB abundance, and for DO below
      a WQC of 5.0 mg L-1 designated for lower South Bay (LSB) and South Bay (SB). We
      submit these thresholds as a basis to assess eutrophication status of SFB and to
      inform nutrient management actions. This approach is transferrable to other
      estuaries to derive chl-a thresholds protective against eutrophication.

PMID- 30220765
TI  - Four decades of water quality change in the upper San Francisco Estuary.
AB  - Quantitative descriptions of chemical, physical, and biological characteristics
      of estuaries are critical for developing an ecological understanding of drivers
      of change. Historical trends and relationships between key species of dissolved
      inorganic nitrogen (ammonium, nitrate/nitrite, total) from the Delta region of
      the San Francisco Estuary were modeled with an estuarine adaptation of the
      Weighted Regressions on Time, Discharge, and Season (WRTDS). Analysis of flow
      normalized data revealed trends that were different from those in the observed
      time-series. Flow-normalized data exhibited changes in magnitude and even
      reversal of trends relative to the observed data. Modelled trends demonstrated
      that nutrient concentrations were on average higher in the last twenty years
      relative to the earlier periods of observation, although concentrations have been
      slowly declining since the mid-1990s and early 2000s. We further describe
      mechanisms of change with two case studies that evaluated 1) downstream changes
      in nitrogen following upgrades at a wastewater treatment plant, and 2)
      interactions between biological invaders, chlorophyll, macro-nutrients (nitrogen
      and silica), and flow in Suisun Bay. WRTDS results for ammonium trends showed a
      distinct signal as a result of upstream wastewater treatment plant upgrades, with
      specific reductions observed in the winter months during low-flow conditions.
      Results for Suisun Bay showed that chlorophyll a production in early years was
      directly stimulated by flow, whereas the relationship with flow in later years
      was indirect and influenced by grazing pressure. Although these trends and
      potential causes of change have been described in the literature, results from
      WRTDS provided an approach to test alternative hypotheses of spatiotemporal
      drivers of nutrient dynamics in the Delta.

PMID- 30220767
TI  - Automatic segmentation of the prostate on CT images using deep learning and multi
      atlas fusion.
AB  - Automatic segmentation of the prostate on CT images has many applications in
      prostate cancer diagnosis and therapy. However, prostate CT image segmentation is
      challenging because of the low contrast of soft tissue on CT images. In this
      paper, we propose an automatic segmentation method by combining a deep learning
      method and multi-atlas refinement. First, instead of segmenting the whole image,
      we extract the region of interesting (ROI) to delete irrelevant regions. Then, we
      use the convolutional neural networks (CNN) to learn the deep features for
      distinguishing the prostate pixels from the non-prostate pixels in order to
      obtain the preliminary segmentation results. CNN can automatically learn the deep
      features adapting to the data, which are different from some handcrafted
      features. Finally, we select some similar atlases to refine the initial
      segmentation results. The proposed method has been evaluated on a dataset of 92
      prostate CT images. Experimental results show that our method achieved a Dice
      similarity coefficient of 86.80% as compared to the manual segmentation. The deep
      learning based method can provide a useful tool for automatic segmentation of the
      prostate on CT images and thus can have a variety of clinical applications.

PMID- 30220766
TI  - Stigma-Based Bullying Interventions: A Systematic Review.
AB  - Youth living with socially devalued characteristics (e.g., minority sexual
      orientation, race, and/or ethnicity; disability; obesity) experience frequent
      bullying. This stigma-based bullying undermines youths' wellbeing and academic
      achievement, with lifelong consequences. The National Academies of Sciences,
      Engineering, and Medicine recommends developing, implementing, and evaluating
      evidence-based interventions to address stigma-based bullying. To characterize
      the existing landscape of these interventions, we conducted a systematic review
      of stigma-based bullying interventions targeting youth in any country published
      in the peer-reviewed literature between 2000 and 2015. Our analysis was guided by
      a theoretical framework of stigma-based bullying, which describes stigma-related
      factors at the societal, structural, interpersonal, and individual levels that
      lead to stigma-based bullying. We screened 8,240 articles and identified 22
      research studies describing 21 interventions addressing stigma-based bullying. We
      found that stigma-based bullying interventions are becoming more numerous, yet
      are unevenly distributed across stigmas, geographic locations, and types of
      organizations. We further found that these interventions vary in the extent to
      which they incorporate theory and have been evaluated with a wide range of
      research designs and types of data. We recommend that future work address stigma
      based bullying within multicomponent interventions, adopt interdisciplinary and
      theory-based approaches, and include rigorous and systematic evaluations.
      Intervening specifically on stigma-related factors is essential to end stigma
      based bullying and improve the wellbeing of youth living with socially devalued
      characteristics.

PMID- 30220768
TI  - A new method to quantify fiber orientation similarity in registered volumes.
AB  - Differences in fiber orientations between registered image volumes can be
      difficult to quantify. Angular errors between diffusion tensor imaging (DTI)
      volumes are often a combination of image registration errors and fluctuations of
      diffusion values that are used to determine the fiber orientations. In order to
      properly quantify the similarity between two images containing fiber orientation
      information, both displacement and angular fluctuation should be considered. We
      present a method to quantify fiber orientation similarity between registered
      images by allowing small pixel displacements in conjunction with minor angle
      differences. Adjustments to the allowed pixel displacement and degree of angle
      difference can help identify the major factor contributing to the error of fiber
      angles. The proposed method can provide a new metric for the evaluation of the
      fiber orientation difference.

PMID- 30220769
TI  - Interactive iterative relative fuzzy connectedness lung segmentation on thoracic
      4D dynamic MR images.
AB  - Lung delineation via dynamic 4D thoracic magnetic resonance imaging (MRI) is
      necessary for quantitative image analysis for studying pediatric respiratory
      diseases such as thoracic insufficiency syndrome (TIS). This task is very
      challenging because of the often-extreme malformations of the thorax in TIS, lack
      of signal from bone and connective tissues resulting in inadequate image quality,
      abnormal thoracic dynamics, and the inability of the patients to cooperate with
      the protocol needed to get good quality images. We propose an interactive fuzzy
      connectedness approach as a potential practical solution to this difficult
      problem. Manual segmentation is too labor intensive especially due to the 4D
      nature of the data and can lead to low repeatability of the segmentation results.
      Registration-based approaches are somewhat inefficient and may produce inaccurate
      results due to accumulated registration errors and inadequate boundary
      information. The proposed approach works in a manner resembling the Iterative
      Livewire tool but uses iterative relative fuzzy connectedness (IRFC) as the
      delineation engine. Seeds needed by IRFC are set manually and are propagated from
      slice-to-slice, decreasing the needed human labor, and then a fuzzy connectedness
      map is automatically calculated almost instantaneously. If the segmentation is
      acceptable, the user selects "next" slice. Otherwise, the seeds are refined and
      the process continues. Although human interaction is needed, an advantage of the
      method is the high level of efficient user-control on the process and non
      necessity to refine the results. Dynamic MRI sequences from 5 pediatric TIS
      patients involving 39 3D spatial volumes are used to evaluate the proposed
      approach. The method is compared to two other IRFC strategies with a higher level
      of automation. The proposed method yields an overall true positive and false
      positive volume fraction of 0.91 and 0.03, respectively, and Hausdorff boundary
      distance of 2 mm.

PMID- 30220771
TI  - Estimating cardiac fiber orientations in pig hearts using registered ultrasound
      and MR image volumes.
AB  - Heart fiber mechanics can be important predictors in current and future cardiac
      function. Accurate knowledge of these mechanics could enable cardiologists to
      provide a diagnosis before conditions progress. Magnetic resonance diffusion
      tensor imaging (MR-DTI) has been used to determine cardiac fiber orientations.
      Ultrasound is capable of providing anatomical information in real time, enabling
      a physician to quickly adjust parameters to optimize image scans. If known fiber
      orientations from a template heart measured using DTI can be accurately deformed
      onto a cardiac ultrasound volume, fiber orientations could be estimated for the
      patient without the need for a costly MR scan while still providing cardiologists
      valuable information about the heart mechanics. In this study, we apply the
      method to pig hearts, which are a close representation of human heart anatomy.
      Experiments from pig hearts show that the registration method achieved an average
      Dice similarity coefficient (DSC) of 0.819 +/- 0.050 between the ultrasound and
      deformed MR volumes and that the proposed ultrasound-based method is able to
      estimate the cardiac fiber orientation in pig hearts.

PMID- 30220770
TI  - Deep Learning based Classification for Head and Neck Cancer Detection with
      Hyperspectral Imaging in an Animal Model.
AB  - Hyperspectral imaging (HSI) is an emerging imaging modality that can provide a
      noninvasive tool for cancer detection and image-guided surgery. HSI acquires high
      resolution images at hundreds of spectral bands, providing big data to
      differentiating different types of tissue. We proposed a deep learning based
      method for the detection of head and neck cancer with hyperspectral images. Since
      the deep learning algorithm can learn the feature hierarchically, the learned
      features are more discriminative and concise than the handcrafted features. In
      this study, we adopt convolutional neural networks (CNN) to learn the deep
      feature of pixels for classifying each pixel into tumor or normal tissue. We
      evaluated our proposed classification method on the dataset containing
      hyperspectral images from 12 tumor-bearing mice. Experimental results show that
      our method achieved an average accuracy of 91.36%. The preliminary study
      demonstrated that our deep learning method can be applied to hyperspectral images
      for detecting head and neck tumors in animal models.

PMID- 30220772
TI  - Quantifying cancer cell receptors with paired-agent fluorescent imaging: a novel
      method to account for tissue optical property effects.
AB  - Dynamic fluorescence imaging approaches can be used to estimate the concentration
      of cell surface receptors in vivo. Kinetic models are used to generate the final
      estimation by taking the targeted imaging agent concentration as a function of
      time. However, tissue absorption and scattering properties cause the final
      readout signal to be on a different scale than the real fluorescent agent
      concentration. In paired-agent imaging approaches, simultaneous injection of a
      suitable control imaging agent with a targeted one can account for non-specific
      uptake and retention of the targeted agent. Additionally, the signal from the
      control agent can be a normalizing factor to correct for tissue optical property
      differences. In this study, the kinetic model used for paired-agent imaging
      analysis (i.e., simplified reference tissue model) is modified and tested in
      simulation and experimental data in a way that accounts for the scaling
      correction within the kinetic model fit to the data to ultimately extract an
      estimate of the targeted biomarker concentration.

PMID- 30220773
TI  - Deformable Registration of Histological Cancer Margins to Gross Hyperspectral
      Images using Demons.
AB  - Hyperspectral imaging (HSI), a non-contact optical imaging technique, has been
      recently used along with machine learning technique to provide diagnostic
      information about ex-vivo surgical specimens for optical biopsy. The computer
      aided diagnostic approach requires accurate ground truths for both training and
      validation. This study details a processing pipeline for registering the cancer
      normal margin from a digitized histological image to the gross-level HSI of a
      tissue specimen. Our work incorporates an initial affine and control-point
      registration followed by a deformable Demons-based registration of the moving
      mask obtained from the histological image to the fixed mask made from the HS
      image. To assess registration quality, Dice similarity coefficient (DSC) measures
      the image overlap, visual inspection is used to evaluate the margin, and average
      target registration error (TRE) of needle-bored holes measures the registration
      error between the histologic and HSI images. Excised tissue samples from
      seventeen patients, 11 head and neck squamous cell carcinoma (HNSCCa) and 6
      thyroid carcinoma, were registered according to the proposed method. Three
      registered specimens are illustrated in this paper, which demonstrate the
      efficacy of the registration workflow. Further work is required to apply the
      technique to more patient data and investigate the ability of this procedure to
      produce suitable gold standards for machine learning validation.

PMID- 30220774
TI  - Effects of Fluorosurfactant Structure and Concentration on Drug Availability and
      Biocompatibility in Water-in-Perfluorocarbon Emulsions for Pulmonary Drug
      Delivery.
AB  - The efficacy of inhaled antibiotics is often impaired by insufficient drug
      penetration into plugged and poorly ventilated airways. Liquid ventilation with
      perfluorocarbon (PFC) containing emulsified aqueous antibiotics, or antibacterial
      perfluorocarbon ventilation, could potentially improve treatment of respiratory
      infections when used as an adjunct therapy to inhaled antibiotics. The molecular
      structure and concentration of the fluorosurfactant used to stabilize such water
      in-PFC emulsions will have significant effects on the efficacy and safety of the
      resulting treatment. In the present study, emulsions are formulated with
      tobramycin in the aqueous phase using two different fluorosurfactants (termed FSL
      PEG+FSL and FSH-PEG) at varying concentrations (Cfs ). An aqueous gel is used to
      evaluate the availability of emulsified drug to diffuse into an aqueous interface
      (such as mucus or biofilm) for varying emulsion formulations. Lastly, the
      cytotoxicity of the fluorosurfactants is characterized using human alveolar basal
      epithelial cells. Results showed that tobramycin delivery is reduced at low Cfs
      due to inadequate drug emulsification and at large Cfs due to hindered drug
      availability. Thus, maximal delivery occurs at intermediate values of Cfs equal
      to 2 and 10 mg mL-1 for the FSH-PEG and FSL-PEG+FSL fluorosurfactants,
      respectively. The optimal emulsion formulation utilized FSH-PEG and demonstrated
      improved drug delivery relative to previously used formulations while exhibiting
      no cytotoxic effect. This work increases understanding of the physical means of
      pulmonary drug delivery via a water-in-PFC emulsion and represents a critical
      step in optimizing emulsion formulation for safe and effective treatment.

PMID- 30220775
TI  - Patterns of shading tolerance determined from experimental light reduction
      studies of seagrasses.
AB  - A review and analysis of the experimental literature on seagrass shading
      evaluated the relationships among experimental light reduction, experimental
      duration, additional modifying factors and common meadow-scale seagrass response
      metrics to determine whether there were consistent statistical relationships.
      Modifying factors included study latitude, field site depth, season of experiment
      initiation, rhizome connectivity (severed, intact), experiment type (field,
      mesocosm), and seagrass life history strategy. Highly significant, best fit
      linear regression models were found for both biomass and shoot density reduction
      that included light reduction, duration and other modifying variables, although
      unexplained variation in the data were high. Duration of light limitation
      affected extent of response for both metrics, and unexplained variance was
      greatly reduced by analysis of data from durations >60d for shoot density and for
      >60d <120d for biomass. Life history strategy was also a significant factor in
      three of four regression models. While the slopes of the responses were
      relatively similar for biomass and shoot density, unexplained variation was
      generally greater for shoot density than biomass in models for data pooled across
      species. There were highly significant, best fit regression models found for both
      biomass and shoot density for both genus and species level analyses, with the
      extent and duration of light reduction the most important model factors. Season
      of experiment, rhizome status, latitude, and experiment type all were also
      included in multiple models. Biomass regression models again tended to have
      lesser unexplained variation than shoot density models. Life history was
      invariant within genus and species, and separate analyses for data divided among
      Colonizing, Opportunistic, and Persistent strategies found relatively similar,
      best fit regression models among strategies. However, the mean percent reduction
      of both biomass and shoot density was generally lower for the Persistent strategy
      than for the other two life histories, suggesting a greater buffering capacity
      against effects of light reduction for such species. Overall, biomass based
      models explained more of the variance in seagrass response to light reduction
      than shoot density, and may be the preferred response variable for meadow-scale
      impact assessments. The relationships observed may inform management decisions by
      helping define the scope of expected responses of seagrasses in general to the
      range of factors that may reduce light availability to seagrasses.

PMID- 30220776
TI  - A supplementary tool to existing approaches for assessing ecosystem community
      structure.
AB  - Measures of biological or species diversity are central to ecology and
      conservation biology. Although there are several commonly used indices, each has
      shortcomings and all vary in the relative emphasis they place on the number of
      species and their relative abundance. We propose utilizing Fisher Information,
      not as a replacement for existing indices, but as a supplement to other indices
      because it is sensitive to community structure. We demonstrate how Shannon's and
      Simpson's diversity indices quantify the diversity of two different systems and
      how Fisher Information can enhance the analyses by comparing, as example, body
      size, and phylogenetic diversity of the different communities. Fisher Information
      is sensitive to the order in which species are entered into the analysis, and
      therefore, it can detect differences in community structure. Thus, the Fisher
      Information index can be useful in helping understand and analyze biodiversity of
      ecosystems and in comparing ecological communities.

PMID- 30220777
TI  - Normal forms of dispersive scalar Poisson brackets with two independent
      variables.
AB  - We classify the dispersive Poisson brackets with one dependent variable and two
      independent variables, with leading order of hydrodynamic type, up to Miura
      transformations. We show that, in contrast to the case of a single independent
      variable for which a well-known triviality result exists, the Miura equivalence
      classes are parametrised by an infinite number of constants, which we call
      numerical invariants of the brackets. We obtain explicit formulas for the first
      few numerical invariants.

PMID- 30220778
TI  - Expansion to abandoned agricultural land forms an integral part of Silver fir
      dynamics.
AB  - Silver fir (Abies alba Mill.) is a tree species distributed mainly in central
      Europe. It once was a dominant tree species within some forests of this region.
      The causes for its rapid decline in the past two centuries have not yet been
      sufficiently explained. It is argued that human activities have been largely
      responsible for expansions and contractions of silver fir populations. On the
      basis of the current distribution of silver fir, historical maps and
      palaeoecological data, we describe the expansion of silver fir forests. We use
      fine resolution at the landscape level, an approach that has so far been
      neglected. Our study areas lies in the northern part of the White Carpathian
      Mountains, Czech Republic. The area comprises 7,045 ha, 65% of which is covered
      by forests. This landscape was shaped by early modern colonization from the 16th
      century onwards and has changed greatly since the decline of its traditional
      utilisation in the 19th and 20th centuries. The area of forests almost doubled
      from 1838 to 2005 while the area of pastures and arable land decreased. We
      identified 172 hectares of silver fir forests by field mapping, which represent
      2.5% of the whole study area and 3.8% of its forested part. We used land use
      history variables (based on subsequent land cover maps from 1838, 1882 and 1956)
      and terrain variables (derived from a digital elevation model) in a logistic
      regression to model the probability of silver fir forest occurrence. Land use
      history was highly significantly correlated with the occurrence of silver fir
      forests. Approximately 59% of silver fir forests occur on land used as pastures
      in 1838, 28% are on former arable land, meadows and fallows, while only 13% have
      been forested continuously since the 19th century. We know from historical
      sources that the surrounding forests (now mainly Norway spruce monocultures) were
      dominated by silver fir up to the 1860s. Silver fir can act as a pioneer species.
      It can invade former agricultural land, which probably ensures the survival and
      periodical expansion of silver fir-dominated forests. Although silver fir has
      been thought to decline under human pressure, we suggest that the opposite may
      occur at the landscape level.

PMID- 30220779
TI  - Field Studies Measuring the Aerosolization of Endotoxin During the Land
      Application of Class B Biosolids.
AB  - Endotoxins are a component of Gram-negative bacteria cell walls and are known to
      be present in biosolids. Endotoxins have been shown to be potent stimulators of
      the innate immune response causing airway irritation and shortness of breath.
      Class B biosolids are routinely applied to agricultural lands to enhance soil
      properties and can be used as an alternative to chemical fertilizers. This study
      investigated the aerosolized endotoxin dispersed during the land application of
      Class B biosolids on agricultural land and a concrete surface at two sites in
      Colorado, USA. Aerosolized endotoxin was captured using HiVol samplers fitted
      with glass fiber filters, polycarbonate filter cassettes (both open and closed)
      and BioSampler impinger air samplers. Endotoxins were also measured in the
      biosolids to allow for correlating bulk biosolids concentrations with aerosol
      emission rates. Endotoxin concentrations in biosolids, impinger solutions and
      filter extracts were determined using the kinetic Limulus amebocyte lysate assay.
      Aerosolized endotoxin concentration was detected from all sites with levels
      ranging from 0.5 to 642 EU/m3. The four types of sampling apparatus were
      compared, and the HiVol and open-faced cassette samplers produced higher time
      weighted average (TWA) measurements (EU/m3) than the impinger and closed cassette
      samplers. Ambient wind speed was found to be the variable best describing the
      observed results with optimal wind speed for highest deposition estimated at 5 m
      s-1. It is argued that HiVol air samplers are a particularly reliable approach
      and subsequent analyses relating TWA measurements to wind speed and biosolids
      characteristics were based on the measurements collected with those samplers.

PMID- 30220780
TI  - EXPLORING SELF-EFFICACY AND PERCEIVED HIV RISK AMONG SOCIOECONOMICALLY
      DISADVANTAGED HISPANIC MEN.
AB  - The prevalence of HIV in Chile predominately affects the male population with the
      primary mode of transmission (99%) through sexual contact. In order to engage in
      safe sexual practices, men must have high sexual self-efficacy and perceived risk
      of infection, however, little research examines these variables with respect to
      HIV prevention. The purpose of this article is to review existing literature on
      self-efficacy and its connection with perceived HIV risk among Hispanic men, in
      order to direct future HIV prevention interventions among Chilean men. A
      literature search was conducted to identify studies for this review using three
      databases. A combination of keywords was used to conduct the search and a total
      of 34 articles were analyzed. All of the articles reviewed examined the Hispanic
      male population with respect to either self-efficacy or perceived risk, or a
      combination of the two. Major themes emerging from the review include: substance
      use, condom use, cultural norms, relationship communication, negotiation, and
      homonegativity. The existing studies provide evidence for preventing future HIV
      infection among low socioeconomic status Chilean males and begin to establish a
      positive relationship between self-efficacy and perceived HIV risk. While
      additional studies are needed to provide further support, self-efficacy and
      perceived risk should be integral aspects of future prevention interventions.

PMID- 30220781
TI  - "I Feel It In My Heart When My Parents Fight": Experiences of 7-9-Year-Old
      Children of Alcoholics.
AB  - Children are vulnerable when exposed to parental alcohol abuse. Although much is
      known about children of alcoholics (COA), research examining the experiences of
      younger COA is scarce. To gain knowledge of the consequences for these children,
      it is important to ask the children themselves. This study explored the
      consequences for a child of having an alcoholic parent, from the point of view of
      7-9-year-old COA. Eighteen children were interviewed, whose alcoholic parent was
      undergoing treatment, using a vignette. In the analysis, using qualitative
      content analysis, the findings show that the children of this young age had much
      experiences and took a great responsibility for their alcoholic parent, and the
      family. The most significant feeling of the children was a feeling of sadness.
      They tried to control the situation in different ways. They wished for a change
      in the future, but despite problems in the family they described things they did
      together with a loving parent. Implications include the importance of listening
      to and supporting all COA, also children as young as 7-9 years old. Further
      studies should address the support that can and should be offered to COA.

PMID- 30220782
TI  - Charting Directions for Research on Immigrant Children Affected by Undocumented
      Status.
AB  - Three groups of children from Mexico and Central America are vulnerable to
      effects of US immigration policies: 1) foreign-born children who entered the US
      with undocumented immigrant parents; 2) unaccompanied children who entered the US
      alone; and 3) U.S.-born citizen children of undocumented immigrant parents.
      Despite the recent demographic growth of these youth, scholarship on their
      strengths and challenges is under-theorized and isolated within specific
      disciplines. Hence, service providers, researchers, and policymakers have
      insufficient research to inform their efforts to support the children's
      wellbeing. A group of scholars and service-providers with expertise in immigrant
      children convened to establish consensus areas and identify gaps in knowledge of
      undocumented, unaccompanied, and citizen children of undocumented immigrant
      parents. The primary goal was to establish a research agenda that increases
      interdisciplinary collaborations, informs clinical practice, and influences
      policies. This report summarizes key issues and recommendations that emerged from
      the meeting.

PMID- 30220783
TI  - Passivity-Based Control with a Generalized Energy Storage Function for Robust
      Walking of Biped Robots.
AB  - This paper offers a novel generalization of a passivity-based, energy tracking
      controller for robust bipedal walking. Past work has shown that a biped limit
      cycle with a known, constant mechanical energy can be made robust to uneven
      terrains and disturbances by actively driving energy to that reference. However,
      the assumption of a known, constant mechanical energy has limited application of
      this passivity-based method to simple toy models (often passive walkers). The
      method presented in this paper allows the passivity-based controller to be used
      in combination with an arbitrary inner-loop control that creates a limit cycle
      with a constant generalized system energy. We also show that the proposed control
      method accommodates arbitrary degrees of underactuation. Simulations on a 7-link
      biped model demonstrate that the proposed control scheme enlarges the basin of
      attraction, increases the convergence rate to the limit cycle, and improves
      robustness to ground slopes.

PMID- 30220784
TI  - Humans do not perceive conspecifics with a greater exposed sclera as more
      trustworthy: a preliminary cross-ethnic study of the function of the overexposed
      human sclera.
AB  - Understanding the adaptive function of the unique morphology of the human eye, in
      particular its overexposed white sclera, may have profound implications for the
      fields of evolutionary behavioural science, and specifically the areas of human
      interaction and social cognition. Existing hypotheses, such as the cooperative
      eye hypothesis, have attracted a lot of attention but remain untested. Here, we:
      (i) analysed variation in the visible sclera size in humans from different ethnic
      backgrounds and (ii) examined whether intraspecific variation of exposed sclera
      size is related to trust. We used 596 facial photographs of men and women,
      assessed for perceived trustworthiness, from four different self-declared racial
      backgrounds. The size of the exposed sclera was measured as the ratio between the
      width of the exposed eyeball and the diameter of the iris (sclera size index,
      SSI). The SSI did not differ in the four examined races and was sexually
      monomorphic except for Whites, where males had a larger SSI than females. In
      general, the association between the SSI and trustworthiness was statistically
      insignificant. An inverted U-shaped link was found only in White women, yet the
      strength of the effect of interaction between sex and race was very small. Our
      results did not provide evidence for the link between exposed sclera size and
      trustworthiness. We conclude that further investigation is necessary in order to
      properly assess the hypotheses relating to the socially relevant functions of
      overexposed sclera.

PMID- 30220785
TI  - Human-accelerated weathering increases salinization, major ions, and
      alkalinization in fresh water across land use.
AB  - Human-dominated land uses can increase transport of major ions in streams due to
      the combination of human-accelerated weathering and anthropogenic salts. Calcium,
      magnesium, sodium, alkalinity, and hardness significantly increased in the
      drinking water supply for Baltimore, Maryland over almost 50 years (p<0.05)
      coinciding with regional urbanization. Across a nearby land use gradient at the
      Baltimore Long-Term Ecological Research (LTER) site, there were significant
      increases in concentrations of dissolved inorganic carbon (DIC), Ca2+, Mg2+, Na+,
      and Si and pH with increasing impervious surfaces in 9 streams monitored bi
      weekly over a 3-4 year period (p<0.05). Base cations in urban streams were up to
      60 times greater than forest and agricultural streams, and elemental ratios
      suggested road salt and carbonate weathering from impervious surfaces as
      potential sources. Laboratory weathering experiments with concrete also indicated
      that impervious surfaces increased pH and DIC with potential to alkalinize urban
      waters. Ratios of Na+ and Cl- suggested that there was enhanced ion exchange in
      the watersheds from road salts, which could mobilize other base cations from
      soils to streams. There were significant relationships between Ca2+, Mg2+, Na+,
      and K+ concentrations and Cl-, SO42-, NO3- and DIC across land use (p<0.05),
      which suggested tight coupling of geochemical cycles. Finally, concentrations of
      Na+, Ca2+, Mg2+, and pH significantly increased with distance downstream (p<0.05)
      along a stream network draining 170 km2 of the Baltimore LTER site contributing
      to river alkalinization. Our results suggest that urbanization may dramatically
      increase major ions, ionic strength, and pH over decades from headwaters to
      coastal zones, which can impact integrity of aquatic life, infrastructure,
      drinking water, and coastal ocean alkalinization.

PMID- 30220786
TI  - SPATIAL DEMOGRAPHIC MODELS TO INFORM CONSERVATION PLANNING OF GOLDEN EAGLES IN
      RENEWABLE ENERGY LANDSCAPES.
AB  - Spatial demographic models can help guide monitoring and management activities
      targeting at-risk species, even in cases where baseline data are lacking. Here,
      we provide an example of how site-specific changes in land-use and other
      anthropogenic stressors can be incorporated into a spatial demographic model to
      investigate effects on population dynamics of Golden Eagles (Aquila chrysaetos).
      Our study focused on a population of Golden Eagles exposed to risks associated
      with rapid increases in renewable energy development in southern California, USA.
      We developed a spatially-explicit, individual-based simulation model that
      integrated empirical data on demography of Golden Eagles with spatial data on the
      arrangement of nesting habitats, prey resources, and planned renewable energy
      development sites. Our model permitted simulated eagles of different stage
      classes to disperse, establish home ranges, acquire resources, prospect for
      breeding sites, and reproduce. The distribution of nesting habitats, prey
      resources, and threats within each individual's home range influenced movement,
      reproduction, and survival. We used our model to explore potential effects of
      alternative disturbance scenarios, and proposed conservation strategies, on the
      future distribution and abundance of Golden Eagles in the study region. Results
      from our simulations suggest that probable increases in mortality associated with
      renewable energy infrastructure (e.g., collisions with wind-turbines and
      vehicles, electrocution on power poles) could have negative consequences for
      population trajectories, but that site-specific conservation actions could reduce
      the magnitude of negative impacts. Our study demonstrates the use of a flexible
      and expandable modeling framework to incorporate spatially dependent processes
      when determining relative risks of proposed management options to Golden Eagles
      and their habitats.

PMID- 30220787
TI  - Neurobiology and Clinical Manifestations of Methamphetamine Neurotoxicity.

PMID- 30220789
TI  - Idiom comprehension in aphasia: Literal interference and abstract representation.
AB  - We investigate three potential mechanisms underlying the deficit in idiom
      comprehension seen in aphasia: difficulty inhibiting literal meanings, inability
      to recognize that a figurative interpretation is required, and difficulty
      processing abstract words and concepts. Unimpaired adults and PWA read high and
      moderate familiarity idioms either preceded or followed by a figuratively biasing
      context sentence. They then completed a string-to-word probe selection task,
      choosing between a figurative target, a literal lure, and unrelated concrete and
      abstract lures. PWA chose the figurative target more often for more familiar
      idioms and after figuratively biasing contexts, suggesting that difficulty
      accessing figurative meanings may be a key contributor to idiom impairment in
      aphasia. Importantly, PWA chose abstract lures at the same rate as they chose
      literal lures, suggesting that abstract lures may be considered equally good
      matches for weak idiomatic representations in PWA, and therefore that idiomatic
      figurative meanings may be represented similarly to abstract concepts for PWA.
      These results have implications for models of idiom comprehension in aphasia, as
      well as the design of future studies of idiom comprehension in PWA.

PMID- 30220788
TI  - Paradoxical olfactory function in combat veterans: The role of PTSD and odor
      factors.
AB  - Stress- and trauma-related disorders, including posttraumatic stress disorder
      (PTSD), are characterized by an increased sensitivity to threat cues. Given that
      threat detection is a critical function of olfaction and that combat trauma is
      commonly associated with burning odors, we sought a better understanding of
      general olfactory function as well as response to specific trauma-related (i.e.
      burning) odors in combat-related PTSD. Trauma-exposed combat veterans with (N =
      22) and without (N = 25) PTSD were assessed for general and specific odor
      sensitivities using a variety of tools. Both groups had similar general odor
      detection thresholds. However, the combat veterans with PTSD, compared to combat
      veterans with comparable trauma exposure, but without PTSD, had increased ratings
      of odor intensity, negative valence, and odor-triggered PTSD symptoms, along with
      a blunted heart rate in response to burning rubber odor. These findings are
      discussed within the context of healthy versus pathological changes in olfactory
      processing that occur over time after psychological trauma.

PMID- 30220790
TI  - Assessment of linguistic and verbal short-term memory components of language
      abilities in aphasia.
AB  - Some current models of aphasia emphasize a role of short-term memory in the
      processing of language and propose that the language impairment in aphasia
      involves impairment to cognitive processes that activate and maintain
      representations of words over the time-period needed to support single word and
      multiple word tasks, including verbal span tasks. This paper reports normative
      data from 39 people with aphasia and 16 age-matched neurotypical controls on a
      test battery for aphasia that assesses effects of increased short-term/working
      memory load on word and sentence processing as well as effects of linguistic
      variations on verbal short-term memory abilities Two concepts are discussed that
      capture the unique potential of this test battery for research and clinical
      practice: specificity of diagnosis and sensitivity to all degrees of aphasia
      severity, including mild aphasia. An analysis is included that shows how the
      performance of individuals with mild aphasia who achieve normal level of
      performance on the Western Aphasia Battery (Kertesz, 2006) show a decline in a
      temporal delay condition that is greater than performance of control
      participants. We also report preliminary data showing differential effects of
      adding a time interval before a response or between items to be compared: reduced
      accuracy for some individuals with aphasia and improved accuracy for others. The
      theoretical and clinical importance of this finding is discussed, as well as the
      overall potential for this test battery to be used in research and as a clinical
      tool. Finally, we discuss the relevance of this test battery to investigate
      functional communication abilities in aphasia.

PMID- 30220792
TI  - From Large Deviations to Semidistances of Transport and Mixing: Coherence
      Analysis for Finite Lagrangian Data.
AB  - One way to analyze complicated non-autonomous flows is through trying to
      understand their transport behavior. In a quantitative, set-oriented approach to
      transport and mixing, finite time coherent sets play an important role. These are
      time-parametrized families of sets with unlikely transport to and from their
      surroundings under small or vanishing random perturbations of the dynamics. Here
      we propose, as a measure of transport and mixing for purely advective (i.e.,
      deterministic) flows, (semi)distances that arise under vanishing perturbations in
      the sense of large deviations. Analogously, for given finite Lagrangian
      trajectory data we derive a discrete-time-and-space semidistance that comes from
      the "best" approximation of the randomly perturbed process conditioned on this
      limited information of the deterministic flow. It can be computed as shortest
      path in a graph with time-dependent weights. Furthermore, we argue that coherent
      sets are regions of maximal farness in terms of transport and mixing, and hence
      they occur as extremal regions on a spanning structure of the state space under
      this semidistance-in fact, under any distance measure arising from the physical
      notion of transport. Based on this notion, we develop a tool to analyze the state
      space (or the finite trajectory data at hand) and identify coherent regions. We
      validate our approach on idealized prototypical examples and well-studied
      standard cases.

PMID- 30220791
TI  - Current knowledge and recent insights into the genetic basis of amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease,
      affecting the upper and/or lower motor neurons. However, extramotor symptoms can
      also occur; cognitive deficits are present in more than 40% of patients and 5-8%
      of ALS patients develop frontotemporal dementia. There is no effective treatment
      for ALS and median survival is 2-3 years after onset. Amyotrophic lateral
      sclerosis is a genetically heterogeneous disorder with monogenic forms as well as
      complex genetic etiology. Currently, complex genetic risk factors are of minor
      interest for routine diagnostic testing or counseling of patients and their
      families. By contrast, a monogenic cause can be identified in 70% of familial and
      10% of sporadic ALS cases. The most frequent genetic cause is a noncoding
      hexanucleotide repeat expansion in the C9orf72 gene. In recent years, high
      throughput sequencing technologies have helped to identify additional monogenic
      and complex risk factors of ALS. Genetic counseling should be offered to all ALS
      patients and their first- and possibly second-degree relatives, and should
      include information about the possibilities and limitations of genetic testing.
      Routine diagnostic testing should at least encompass the most frequently mutated
      disease genes (C9orf72, SOD1, TDP-43, FUS). Targeted sequencing approaches
      including further disease genes may be applied. Caution is warranted as the
      C9orf72 repeat expansion cannot be detected by routine sequencing technologies
      and testing by polymerase chain reaction (PCR) is failure-prone. Predictive
      testing is possible in families in which a genetic cause has been identified, but
      the limitations of genetic testing (i. e., the problems of incomplete penetrance,
      variable expressivity and possible oligogenic inheritance) have to be explained
      to the families.

PMID- 30220793
TI  - Optimisation of ANN topology for predicting the rehydrated apple cubes colour
      change using RSM and GA.
AB  - In this study, an efficient optimisation method by combining response surface
      methodology (RSM) and genetic algorithm (GA) is introduced to find the optimal
      topology of artificial neural networks (ANNs) for predicting colour changes in
      rehydrated apple cubes. A multi-layered feed-forward backpropagation ANN model of
      algorithms was developed to correlate one output (colour change) to four input
      variables (drying air temperature, drying air velocity, temperature of distilled
      water and rehydration time). A predictive model for ANN topology in terms of the
      best mean squared error (MSE) performance on validation samples was created using
      RSM. RSM model was integrated with an effective GA to find the optimum topology
      of ANN. The optimum ANN had minimum MSE when the number of hidden neurons,
      learning rate, momentum constant, number of epochs and number of training runs
      were 13, 0.33, 0.89, 3869 and 3, respectively. MSE of optimal ANN topology on
      validation samples was 0.0072095. It turned out that the optimal ANN topology can
      be considered as more precise for predicting colour change in the rehydrated
      apple cubes. Mean absolute error and regression coefficient (R) of the optimal
      ANN topology were determined as 0.0259 and 0.96475 for training, 0.0399 and
      0.95243 for testing and 0.0264 and 0.95151 for validation data sets. The results
      of the testing model on new samples showed excellent agreement between the actual
      and predicted data with coefficient of determination R2 = 0.97.

PMID- 30220794
TI  - Investment in human resources improves eye health for all.

PMID- 30220795
TI  - Human resources for eye health: ensuring a smooth pipeline.

PMID- 30220796
TI  - Selecting and training candidates to suit their role.

PMID- 30220797
TI  - My journey: from clinician to educator.

PMID- 30220798
TI  - Developing training programmes for eye teams.

PMID- 30220799
TI  - Competency training: Using the ICO cataract rubric to learn and teach cataract
      surgery.

PMID- 30220800
TI  - Recruiting for local needs.

PMID- 30220801
TI  - Recruiting and distributing eye health workers.

PMID- 30220802
TI  - How to create a balanced eye team: an example from Malawi.

PMID- 30220803
TI  - Policy making to address imbalances in human resources for eye health in rural
      Kenya.

PMID- 30220804
TI  - Retention through career development: on-the-job training in Trinidad.

PMID- 30220806
TI  - Investing to improve conditions for retention and satisfaction at a paediatric
      eye centre in South Sulawesi, Indonesia.

PMID- 30220805
TI  - Encouraging eye care workers to stay: the role of investment and management.

PMID- 30220807
TI  - Guatemala: How we create a welcoming workplace for our staff and patients.

PMID- 30220808
TI  - Tips for team management.

PMID- 30220809
TI  - Leading and managing a team.

PMID- 30220810
TI  - How to enhance your own development as a teacher and learner.

PMID- 30220811
TI  - Achieving universal eye health coverage: planning and human resource lessons from
      trachoma.

PMID- 30220812
TI  - Picture quiz.

PMID- 30220813
TI  - Human Resources for eye health in South Asia.

PMID- 30220814
TI  - Paediatric eye care team: a comprehensive approach.

PMID- 30220815
TI  - Competency-based assessment as a reliable skill building strategy for allied
      ophthalmic personnel.

PMID- 30220816
TI  - Building an eye care team in rural areas: a central Indian case study.

PMID- 30220817
TI  - Nepal: self-reliant in ophthalmic human resources.

PMID- 30220818
TI  - Football to eyeball: thinking out of the box to create an ophthalmic talent pool
      in difficult geographies.

PMID- 30220819
TI  - Effective engagement of community health workers in primary eye care in India.

PMID- 30220820
TI  - Evidence-based management of eye care delivery.

PMID- 30220821
TI  - VISION 2020 INDIA's annual conference.

PMID- 30220822
TI  - Optimal Bayesian estimators for latent variable cluster models.
AB  - In cluster analysis interest lies in probabilistically capturing partitions of
      individuals, items or observations into groups, such that those belonging to the
      same group share similar attributes or relational profiles. Bayesian posterior
      samples for the latent allocation variables can be effectively obtained in a wide
      range of clustering models, including finite mixtures, infinite mixtures, hidden
      Markov models and block models for networks. However, due to the categorical
      nature of the clustering variables and the lack of scalable algorithms, summary
      tools that can interpret such samples are not available. We adopt a Bayesian
      decision theoretical approach to define an optimality criterion for clusterings
      and propose a fast and context-independent greedy algorithm to find the best
      allocations. One important facet of our approach is that the optimal number of
      groups is automatically selected, thereby solving the clustering and the model
      choice problems at the same time. We consider several loss functions to compare
      partitions and show that our approach can accommodate a wide range of cases.
      Finally, we illustrate our approach on both artificial and real datasets for
      three different clustering models: Gaussian mixtures, stochastic block models and
      latent block models for networks.

PMID- 30220823
TI  - Fine-tuning ADAS algorithm parameters for optimizing traffic safety and mobility
      in connected vehicle environment.
AB  - Under the Connected Vehicle environment where vehicles and road-side
      infrastructure can communicate wirelessly, the Advanced Driver Assistance Systems
      (ADAS) can be adopted as an actuator for achieving traffic safety and mobility
      optimization at highway facilities. In this regard, the traffic management
      centers need to identify the optimal ADAS algorithm parameter set that leads to
      the optimization of the traffic safety and mobility performance, and broadcast
      the optimal parameter set wirelessly to individual ADAS-equipped vehicles. Once
      the ADAS-equipped drivers implement the optimal parameter set, they become active
      agents that work cooperatively to prevent traffic conflicts, and suppress the
      development of traffic oscillations into heavy traffic jams. Measuring systematic
      effectiveness of this traffic management requires am analytic capability to
      capture the quantified impact of the ADAS on individual drivers' behaviors and
      the aggregated traffic safety and mobility improvement due to such an impact. To
      this end, this research proposes a synthetic methodology that incorporates the
      ADAS-affected driving behavior modeling and state-of-the-art microscopic traffic
      flow modeling into a virtually simulated environment. Building on such an
      environment, the optimal ADAS algorithm parameter set is identified through a
      multi-objective optimization approach that uses the Genetic Algorithm. The
      developed methodology is tested at a freeway facility under low, medium and high
      ADAS market penetration rate scenarios. The case study reveals that fine-tuning
      the ADAS algorithm parameter can significantly improve the throughput and reduce
      the traffic delay and conflicts at the study site in the medium and high
      penetration scenarios. In these scenarios, the ADAS algorithm parameter
      optimization is necessary. Otherwise the ADAS will intensify the behavior
      heterogeneity among drivers, resulting in little traffic safety improvement and
      negative mobility impact. In the high penetration rate scenario, the identified
      optimal ADAS algorithm parameter set can be used to support different control
      objectives (e.g., safety improvement has priority vs. mobility improvement has
      priority).

PMID- 30220824
TI  - Photocatalytic oxidation of aromatic amines using MnO2@g-C3N4.
AB  - An efficient and direct oxidation of aromatic amines to aromatic azo-compounds
      has been achieved using a MnO2@g- C3N4 catalyst under visible light as a source
      of energy at room temperature.

PMID- 30220825
TI  - Effects of Isophorone Diisocyanate on the Thermal and Mechanical Properties of
      Shape-Memory Polyurethane Foams.
AB  - Previously developed shape-memory polymer foams display fast actuation in water
      due to plasticization of the polymer network. The actuation presents itself as a
      depression in the glass-transition temperature when moving from dry to aqueous
      conditions; this effect limits the working time of the foam to 10 min when used
      in a transcatheter embolic device. Reproducible foams are developed by altering
      the chemical backbone, which can achieve working times of greater than 20 min.
      This is accomplished by incorporating isophorone diisocyanate into the foam,
      resulting in increased hydrophobicity, glass transitions, and actuation time.
      This delayed actuation, when compared with previous systems, allows for more
      optimal working time in clinical applications.

PMID- 30220826
TI  - Why Is Theory of Mind Important for Referential Communication?
AB  - This research studies the relation between children's Theory of Mind (ToM) and
      the communicative behaviour and strategies used in a referential communication
      task. A total of 46 children (aged 6 to 10) were administered 6 ToM tasks, and
      they also participated in pairs in a cooperative task. Each pair built 4
      construction models. Results showed that several ToM skills were related to the
      communicative behaviours of requesting clarification and giving information. In
      addition, the most used communicative strategy was Joint review, in which
      participants reviewed together the location of their blocks. This strategy was
      the most related to ToM abilities and to cooperative success. The importance of
      ToM for developing the communicative behaviours and strategies necessary for
      cooperation is discussed.

PMID- 30220827
TI  - Transdisciplinarity in Research: Perspectives of Early Career Faculty.
AB  - Background: Early career faculty experiences and perspectives on
      transdisciplinary research are important yet understudied. Methods: Assistant
      professors at 50 top-ranked social work programs completed an online survey
      assessing perspectives on the salience of transdisciplinary training in their
      field, obstacles to or negative impacts of transdisciplinary training, and
      current environments. Content analysis and descriptive statistics were used.
      Results: A large majority of all participants (N 1/4 118) believed that
      transdisciplinary research is important, that greater training is needed, and
      that they are relatively well prepared in related skill sets. They are expected
      to build cross-disciplinary collaborations, yet only a small minority believed
      that social work researchers are nationally recognized as important
      collaborators, or that they are prepared to navigate tensions on research teams.
      Conclusions: We offer a multilevel framework of structural and training supports
      needed to realize transdisciplinary research in social work with relevance to
      other disciplines.

PMID- 30220828
TI  - HTS Shim Coils Energized by a Flux Pump for the MIT 1.3-GHz LTS/HTS NMR magnet:
      Design, Construction, and Results of a Proof-of-Concept Prototype.
AB  - In this paper we present design, construction, and preliminary results of a proof
      of-concept prototype of high-temperature superconductor (HTS) shim coils operated
      at 77 K and energized, for the first time among all shim coils, by a flux pump,
      here called digital flux injector (DFI). Although the prototype shims were wound
      with 2-mm wide REBCO tape, and DFI with Bi2223 and REBCO tapes, the HTS Z1 and Z2
      shims to be installed in the MIT 1.3-GHz LTS/HTS NMR magnet (1.3G) currently
      under construction and operated at 4.2 K will be wound with reinforced Bi2212
      wire and DFI with Nb3Sn tape. The paper concludes with two sets of Bi2212 Z1 and
      Z2 shims for 1.3G.

PMID- 30220829
TI  - Modeling Strategies for Superconducting Microstrip Transmission Line Structures.
AB  - Strategies are explored to reduce the electromagnetic simulation time of
      electrically large superconducting transmission line structures while retaining
      model accuracy. The complex surface reactance of an infinite thin-film
      superconducting sheet is evaluated with the BCS (Bardeen-Cooper-Schrieffer)
      theory and used as an input to model the phase velocity and characteristic
      impedance of finite width transmission line structures. Commercially available
      electromagnetic simulation software are employed for the calculations and the
      results are compared with limiting analytic forms from the literature. The
      influences of line width, metallization thickness, and substrate height on
      microstrip transmission line propagation are considered in detail and a scaling
      approach is presented to compensate for the leading order effect in numerical
      simulations. These findings are particularly important near the energy gap of the
      superconductor due to the influence of the kinetic inductance on the transmission
      line dispersion.

PMID- 30220830
TI  - Novel triazoles of 3-acetylbetulin and betulone as anticancer agents.
AB  - The CuAAC reaction of azides and acetylenic triterpenes was used for synthesis of
      new triazoles of 3-acetylbetulin and betulone. The triazole derivatives were
      evaluated for their anticancer activity in vitro against amelanotic melanoma C
      32, ductal carcinoma T47D and glioblastoma SNB-19 cell lines. 28-[1-(3'
      Deoxythymidine-5'-yl)-1H-1,2,3-triazol-4-yl]carbonylbetulone 6e exhibited a
      significant IC50 value (0.17 uM) against the human glioblastoma SNB-19 cell line,
      an almost 5-fold higher potency while compared with reference cisplatin.

PMID- 30220831
TI  - Thiazoles with cyclopropyl fragment as antifungal, anticonvulsant, and anti
      Toxoplasma gondii agents: synthesis, toxicity evaluation, and molecular docking
      study.
AB  - Synthesis and investigation of antifungal, anticonvulsant and anti-Toxoplasma
      gondii activities of ten novel (2-(cyclopropylmethylidene)hydrazinyl)thiazole 3a
      3j are presented. Among the derivatives, compounds 3a-3d and 3f-3j possess very
      high activity against Candida spp. ATCC with MIC = 0.015-7.81 ug/ml. Compounds 3a
      3d and 3f-3j possess also very high activity towards most of strains of Candida
      spp. isolated from clinical materials with MIC = 0.015-7.81 ug/ml. The activity
      of these compounds is similar and even higher than the activity of nystatin used
      as positive control. Additionally, compounds 3c and 3e showed interesting
      anticonvulsant activities in the MES test, whereas compounds 3f and 3i
      demonstrated the anticonvulsant activity in PTZ-induced seizures. Noteworthy,
      none of these compounds impaired animals' motor skills in the rotarod test.
      Moreover, thiazoles 3a, 3h, and 3j showed significant anti-Toxoplasma gondii
      activity, with IC50 values 31-52 times lower than those observed for
      sulfadiazine. The results of the cytotoxicity evaluation, anti-Candida spp. and
      anti-Toxoplasma gondii activity studies showed that Candida spp. and Toxoplasma
      gondii growth was inhibited at non-cytotoxic concentrations for the mouse L929
      fibroblast and the African green monkey kidney (VERO) cells. Molecular docking
      studies indicated secreted aspartic proteinase (SAP) as possible antifungal
      target.

PMID- 30220832
TI  - Evaluation of the effect of 2-(2,4-dihydroxyphenyl)-4H-benzofuro[3,2
      d][1,3]thiazin-4-one on colon cells and its anticancer potential.
AB  - In this paper, we present the biological effect of the newly synthesized 2-(2,4
      dihydroxyphenyl)-4H-benzofuro[3,2-d][1,3]thiazin-4-one (DPBT) on human colon
      adenocarcinoma cell lines (HT-29 and LS180). Additionally, DPBT cytotoxicity was
      examined in human colon epithelial cells (CCD 841 CoTr) and human skin
      fibroblasts (HSF). The studies revealed a significant decrease in the
      proliferation of cancer cells after exposure to DPBT at concentrations in the
      range of 10-100 uM. Additionally, DPBT was not toxic to normal CCD 841 CoTr and
      HSF cells at concentrations that induced inhibition of cancer cell proliferation.
      The nature of the anti-proliferative action of DPBT in the cell cycle progression
      in colon cancer cells and the expression of proteins involved in this process
      were examined by flow cytometry and western blotting, respectively. The
      investigations demonstrated higher sensitivity of LS180 than HT-29 to the DPBT
      treatment. The anti-proliferative action of DPBT in LS180 was attributed to cell
      cycle arrest in the G1 phase via up-regulation of p27KIP1 and down-regulation of
      cyclin D1 and CDK4 proteins.

PMID- 30220833
TI  - Self-Injurious Behavior in People with Intellectual Disabilities and Co-Occurring
      Psychopathology using the Self-Harm Scale: A Pilot Study.
AB  - Self-injurious behavior (SIB) is one of the most detrimental behaviors for the
      person showing it, as well as for their environment. Nevertheless, structured
      clinical assessments of SIB are scarce. Staff completed a Self-Harm Scale (SHS)
      every time they witnessed SIB in clients with an intellectual disability (ID) and
      co-occurring psychopathology (N = 33). Descriptive statistics were conducted to
      explore the nature of the incidents of SIB and the characteristics of the people
      involved in the incidents. In 41 weeks, 104 SIB incidents were reported for 8 out
      of 33 clients (24%). Incidents were most prevalent on Mondays (23%). As far as
      the methods of SIB concerned, cutting was the most used method (63%). Clients who
      showed SIB differed significantly from clients who did not on gender, having a
      personality disorder and communicative abilities. This study was one of the few
      that used an incident-based record form to report SIB by direct observation. It
      is hoped that the SHS helps to gain more information about SIB, to improve
      individualized interventions. Further research is necessary to determine the
      psychometric properties and clinical utility of the scale.

PMID- 30220834
TI  - Observational Assessment of Engagement Strategies to Promote Parent Homework
      Planning in Community-Based Child Mental Health Treatment: A Pilot Study.
AB  - Therapy homework includes tasks given to clients to complete outside of session
      to facilitate new knowledge/skills or to advance treatment goals. Homework
      completion, an important element of parent engagement in child mental health (MH)
      treatment, has been associated with improved child outcomes. The current pilot
      study assessed the design/assign phase of the therapy homework process to examine
      a) the extent to which therapists implemented engagement strategies with parents
      and b) whether therapist deployment of engagement strategies in early treatment
      predicted subsequent parent participation in homework planning. We included an
      ethnically-diverse sample of 10 therapists and 11 parent/child dyads receiving
      community-based MH services who participated in a pilot intervention study. Two
      observational coding systems were developed to code treatment session recordings
      for the extent to which a) therapists implemented engagement strategies with
      parents and b) parents contributed to therapy homework planning. Findings
      revealed low extensiveness of therapist implementation of engagement strategies
      with parents. As hypothesized, therapist use of engagement strategies
      (Collaboration, Empowerment, and Psychoeducation) in early treatment
      significantly predicted subsequent parent homework planning (sharing perspective
      on homework planning). However, therapist use of Alliance was unrelated to parent
      homework planning. These preliminary results suggest that therapist
      implementation of engagement strategies in early treatment may promote parent
      participation in homework planning, which is an important precursor to homework
      completion. This pilot study suggests potential future directions for both
      research on and training for community-based therapists in implementing
      successful strategies to promote parent homework planning in child MH treatment.

PMID- 30220835
TI  - Race-Related Content of Animated Cartoons.
AB  - Relying upon a content analysis of 1 specific type of medium to which young
      people are exposed beginning at an early age, on a regular basis, and for many
      years (i.e., animated cartoons), the present study examines what types of
      messages are provided about being members of different racial groups. This
      research examines the following issues: (a) How prevalent are race-related
      content and overt acts of racism in animated cartoons? (b) Has this prevalence
      changed over time? (c) What "types" of characteristics tend to be associated with
      being Caucasian, African American, Latino, Native American, and Asian? Results
      indicate that the prevalence of racial minority groups has been low over the
      years, with gradual decreases in representation during recent years, when the
      American population of racial minorities has grown. As time has gone on, the
      presence of overt racism has decreased greatly, demonstrating particularly sharp
      declines in the years since the Civil Rights Movement of the 1960s. On most
      dimensions studied, members of different races were portrayed similarly.

PMID- 30220836
TI  - Engaging Undergraduate Kinesiology Students in Clinically-Based Research.
AB  - Many undergraduate students in kinesiology are interested in clinical careers and
      seek research opportunities for advanced study and unique learning experiences.
      This paper describes a process of engaging undergraduate students in a multi
      disciplinary, NIH-funded Program Project investigating factors that may affect
      pelvic floor support and symptoms in primiparous women during the first year
      postpartum. Students complete general and protocol-specific training prior to
      engagement, have specific tasks that reinforce skill development and require
      independence, and are invited to participate in additional opportunities with the
      investigative team. The topic of pelvic floor health is novel to most students
      and participation in this research expands their knowledge beyond a mainstream
      kinesiology curriculum. Institutionalizing this type of program could formalize
      undergraduate student research experiences and facilitate ongoing clinical
      research efforts with a kinesiology focus.

PMID- 30220837
TI  - One Step at a Time: A Latent Transitional Analysis on Changes in Substance Use,
      Exposure to Violence, and HIV/AIDS Risk Behaviors among Female Offenders.
AB  - The aim of this analysis is to identify latent subgroups of women based on
      substance use, exposure to violence, and risky sexual behaviors and quantify
      discrete stages of behavior change over time. Data comes from 317 women recruited
      from a Municipal Drug Court System in the Midwest. All participants were
      interviewed regarding their substance use and sexual behaviors, as well as their
      exposure to violence at baseline, a 4th-month follow-up, and an 8th-month follow
      up. A latent transitional analysis (LTA), a longitudinal extension of a latent
      class analysis (LCA), was used to quantify discrete stages of behavior change.
      The results of our analyses revealed 4 distinct behavioral profiles in our
      sample: 1) women with high probabilities of risky sexual behaviors, exposure to
      violence, and crack/cocaine use, 2) women with a high probability of exposure to
      violence, and moderate sexual risk taking, 3) women characterized solely by a
      high probability of crack/cocaine use, 4) women with low probabilities of all
      factors. The proportion of women in latent statuses characterized by a high
      probability of crack/cocaine use did not substantially decrease over time. Women
      who experienced child sexual abuse, had a greater number of lifetime arrests,
      were older, and believed they had risky drug using behavior that needed changing
      at baseline were significantly more likely to be in higher-risk latent statuses.
      Targeted interventions tailored to crack/cocaine users, as well as a wide-spread
      need for trauma-informed interventions among females involved in the criminal
      justice system, are needed.

PMID- 30220838
TI  - Systemic lupus erythematosus-associated diffuse alveolar hemorrhage: A case
      report and review of the literature.
AB  - Systemic lupus erythematosus is associated with numerous pleuropulmonary
      complications. Although uncommon, diffuse alveolar hemorrhage represents a life
      threatening cause of acute respiratory failure among patients with lupus. Here,
      we present a 24-year-old woman with a history of lupus who developed hemoptysis
      and respiratory failure associated with diffuse radiographic infiltrates and
      anemia. Bronchoscopy confirmed diffuse alveolar hemorrhage. She was managed with
      supportive care, plasmapheresis, and immunosuppressive pharmacotherapy leading to
      sustained resolution of her pulmonary hemorrhage and respiratory failure. We then
      review the available literature on the pathophysiology and management of lupus
      associated diffuse alveolar hemorrhage, which centers on supportive care,
      reversal of coagulopathy, and immunosuppressive measures.

PMID- 30220839
TI  - Addressing Weight Suppression to Improve Treatment Outcome for Bulimia Nervosa.
AB  - Cognitive behavioral therapy (CBT) is regarded as the gold-standard treatment for
      bulimia nervosa (BN), yet despite impressive empirical support for its
      effectiveness, over 50% of patients fail to achieve abstinence from binge eating
      and purging by the end of treatment. One factor that may contribute to reduced
      efficacy rates in CBT is weight suppression (WS; the difference between a
      person's highest weight ever at their adult height and current weight). A growing
      body of research indicates that WS in patients with BN may have a clinically
      significant effect on symptomatology and prognosis. However, the current
      cognitive behavioral framework for BN does not explicitly acknowledge the role of
      WS in the onset or maintenance of BN symptoms and does not provide guidance for
      clinicians on how to address WS during treatment. The relationship between WS,
      biological pressure to regain lost weight, and the maintenance of BN symptoms
      suggest that current cognitive behavioral models of BN may be improved by
      considering the role of WS and exploring needed treatment modifications. Indeed,
      a reconceptualization of existing models may offer insight into potential
      strategies that can be used to reduce the susceptibility to treatment dropout,
      nonresponse, and relapse. It is therefore necessary to consider whether, and how,
      clinicians' consideration of WS during case conceptualization and treatment
      planning could serve to improve CBT outcomes. The current review explores ways in
      which high WS could contribute to poor CBT outcomes, provides preliminary
      clinical recommendations for incorporating WS into existing cognitive behavioral
      treatments based on extant data and clinical wisdom, and proposes suggestions for
      future research needed in this domain.

PMID- 30220840
TI  - Patterns of functional diversity of two trophic groups after canopy thinning in
      an abandoned coppice.
AB  - Coppice abandonment had negative consequences for biodiversity of forest
      vegetation and several groups of invertebrates. Most coppicing restoration
      studies have focused only on a single trophic level despite the fact that
      ecosystems are characterized by interactions between trophic levels represented
      by various groups of organisms. To address the patterns of functional diversity
      in the perspective of coppicing restoration, we studied the short-term effects of
      conservation-motivated tree canopy thinning in an abandoned coppice-with
      standards in Central Europe, a region where such attempts have been rare so far.
      The functional diversity of vascular plants and spiders, chosen as two model
      trophic groups within a forest ecosystem, was compared between thinned and
      control forest patches. To characterize functional patterns, we examined several
      functional traits. These traits were assigned into two contrasting categories:
      response traits reflecting a change of environment (for both vascular plants and
      spiders) and effect traits influencing the ecosystem properties (only for
      vascular plants). Functional diversity was analysed by CCA using two measures:
      community-weighted means (CWM) and Rao's quadratic diversity (RaoQ). CCA models
      revealed that the canopy thinning had a positive effect on diversity of the
      response traits of both trophic groups and negatively influenced the diversity of
      effect traits. In addition, we found distinct seasonal dynamics in functional
      diversity of the spider communities, which was probably linked to leaf phenology
      of deciduous trees and therefore an effect trait not directly examined in this
      study. We conclude that canopy thinning affected functional diversity across
      trophic groups during the initial phase of coppicing restoration. With necessary
      precautions, careful canopy thinning can be effectively applied in the
      restoration of functional diversity in abandoned coppices.

PMID- 30220841
TI  - Dynamics of herbaceous vegetation during four years of experimental coppice
      introduction.
AB  - Understanding the effects of coppicing on forest ecosystems is important for
      progress towards sustainable forest management. A newly established coppicing
      experiment in a secondary temperate deciduous forest in the SE Czech Republic
      provides a rather unique insight into succession driven by canopy thinning in a
      forest still lacking species typical for forests established since long time ago.
      Herbaceous layer vegetation was monitored for four subsequent years in 2012-2015.
      We focused on the influence of canopy thinning intensity in two different forest
      types defined by dominant tree species (oak and lime). Our results showed that
      the opening of the canopy had immediate effects on herbaceous vegetation.
      Coverage, species richness and compositional patterns followed the coppicing
      intensity gradient. The dominant tree species had contrasting effects. Under oak,
      the reaction to coppicing was weak. Under lime, strong reaction both related to
      coppicing intensity and temporal development was observed. Herbs with short life
      cycle had the greatest contribution, but perennial grasses also began to increase
      their coverage after coppicing. Several invasive species, mostly short-lived
      herbs, emerged but are supposed to retreat as the succession will proceed. We
      conclude that coppice introduction to a secondary forest led to contrasting
      patterns related to dominant tree species. The marked difference was probably due
      to the slow sucession towards a future forest community saturated by species.
      This process may be now further diversified by coppicing management.

PMID- 30220842
TI  - Stroke medicine in antiquity: The Greek and Muslim contribution.
AB  - The collective human effort to understand the brain and its common disease,
      stroke, has spanned many centuries, cultures, and societies. The ancient Greek
      and Muslim physicians made important contributions to the understanding and
      management of stroke in their time. The Muslim physicians, from 800 to 1200 AD,
      played an outstanding role, by conserving and refining Greco-Roman philosophies,
      formulating their own theories and reaching conclusions, some of which match our
      modern stroke models. They recognized the importance of the brain as a source of
      stroke symptoms, proposed the vascular nature of stroke etiology, and had some
      thoughts about intra-ventricular hemorrhage, and the process of atherosclerosis
      with the help of ancient philosophies. Their management strategies have now been
      discarded, but some of the herbal medicines they used, may be useful in stroke
      management today. Therefore, more research is required into the ancient texts to
      evaluate the efficacy of their management strategies.

PMID- 30220843
TI  - Gender-specific differences in the awareness and intake of Vitamin D among adult
      population in Qassim Region.
AB  - BACKGROUND: Despite the abundance of sunshine throughout the year, Vitamin D
      deficiency is highly prevalent among different Saudi populations. The objective
      of the current study was to evaluate the awareness and intake of Vitamin D and
      their association among adults of both genders. MATERIALS AND METHODS: A cross
      sectional study was done between June and August 2016 among adult patients and
      their family members (>18 years) presenting at 6 Primary Care Centers in the
      Qassim region, Saudi Arabia. RESULTS: A total of 500 study participants were
      included in the study; 54.6% of the participants were males and mostly aged most
      between 26-50 years. The majority of the participants had heard of Vitamin D
      (91.4%), believed in its importance for health (92.8%), were aware of the
      symptoms of Vitamin D deficiency (72.6%), and were able to identify exposure to
      sunlight (81.4%) and diet (70.4%) as sources. The sources of Vitamin D used by
      the participants were exposure to the sun (57.2%), Vitamin D-rich foods (51.2%)
      and supplements (18.8%). There was a significant association between overall
      awareness of Vitamin D and intake of at least 2 sources of Vitamin D in males (P
      < 0.001) but not females (P = 0.920). Although females had better awareness than
      males, exposure to the sun was much lower in females than males. CONCLUSION: As
      supplementation was very low in both genders, and since cultural factors that
      limit females' exposure to the sun are not easily modifiable, the current
      findings further underline the critical importance of Vitamin D supplementation,
      particularly in females in Saudi Arabia.

PMID- 30220844
TI  - Association between air pollutants and anthropometric measurements of boys in
      primary schools in Dammam, Eastern Saudi Arabia.
AB  - BACKGROUND: The combined action of biological, physical, and chemical agents in
      the environment impacts on children's health resulting in illness and disability.
      Body measurements provide the optimum method of evaluating the health status of
      children. This study was done to measure the main air pollutants that affect the
      physical growth of primary schoolboys and compare the growth patterns of these
      young boys in three different areas in the city of Dammam in the Eastern Province
      of Saudi Arabia. MATERIALS AND METHODS: A cross-sectional survey was conducted in
      three different environmental areas (residential, commercial, and industrial).
      The total number of boys in the study was 851. Data were collected using a self
      administered questionnaire with three main parts: sociodemographic,
      anthropometric measurements, and air pollutant measurements. RESULTS: Less than
      half the children (45%) residing in the residential area belonged to Classes 4
      and 5 socioeconomic groups. In addition, 56.6% of the children residing in the
      commercial area and 26.5% of children in the industrial area belonged to the same
      socioeconomic class. There was a statistically significant difference between the
      mean age (P < 0.01), nationality, and the number of rooms and bedrooms (P <
      0.001) in the boys' homes. Furthermore, there were statistically significant
      differences in weight (P < 0.05), height (P < 0.001), and height for age
      according to international standards (P < 0.01). Moreover, arm anthropometry of
      boys living in the residential area was higher than in the other two studied
      areas. Low values of all anthropometric measurements of the studied boys were
      significantly associated with exposure to high levels of nitrogen dioxide (NO2)
      >0.35 parts per million (ppm) or carbon monoxide >35 ppm (Saudi standard)
      outdoors, irrespective of socioeconomic conditions. CONCLUSIONS: The most
      significant factors that affected anthropometric values were total suspended
      particulate concentration in the outdoor air of the studied areas, parental
      education, and/or occupation. It is recommended that steps be taken to reduce
      indoor and outdoor air pollution.

PMID- 30220845
TI  - School absenteeism during menstruation amongst adolescent girls in Delhi, India.
AB  - BACKGROUND: Girls' health and education form the cornerstone of development and
      the gateway to full participation as women in political, economic, and cultural
      life of a country. Poor menstrual hygiene management has been shown to result in
      a sense of shame, anxiety, and embarrassment that contributes to absenteeism and
      poor performance at school. The objectives of this study were to determine the
      percentage of girls absent from school during menstruation, to evaluate the
      various factors associated with school absenteeism during menstruation, and to
      assess the practices regarding menstrual hygiene. MATERIALS AND METHODS: A mixed
      method research of combined cross-sectional study and qualitative research was
      conducted in six government schools of Delhi by means of a questionnaire survey
      and focus group discussions. The sample size was 600 adolescent girls. RESULTS:
      Out of 600, 245 (40%) girls remained absent from school during their
      menstruation. School absenteeism was significantly associated with the type of
      absorbent used, lack of privacy at school, restrictions imposed on girls during
      menstruation, mother's education, and source of information on menstruation.
      Nearly 65% reported that it affected their daily activities at school and that
      they had to miss their class tests and classes as a result of pain, anxiety,
      shame, anxiety about leakage, and staining of their uniform. CONCLUSION: Since
      mothers are the primary source of information, they should be counseled to
      dispose of their taboos about discussing issues related to menstruation. They
      should be taught about the ill effects of adhering to taboos related to
      menstruation. The curriculum on general biology should have more detail on
      menstruation.

PMID- 30220846
TI  - Consumption of vitamin and mineral supplements and its correlates among medical
      students in Eastern Province, Saudi Arabia.
AB  - BACKGROUND: Although vitamin and mineral supplements are popular in many
      countries, few studies have documented their use among college students.
      Moreover, there is not much national data on the use of supplements by Saudi
      medical students. The aim of this study was to determine the prevalence of the
      use of vitamin and mineral supplements by female medical students at Imam
      Abdulrahman Bin Faisal University (IAU) in Dammam, Saudi Arabia, and to identify
      characteristics associated with the use of supplements in this population.
      MATERIALS AND METHODS: For this cross-sectional study, all female medical
      students at IAU in Dammam, Saudi Arabia, were approached during September to
      November 2016. Results were presented as frequency distribution. Chi-square test
      and logistic regression analysis were performed to determine factors associated
      with supplement use; P < 0.05 was considered statistically significant. RESULTS:
      Completed questionnaires were returned by 474 students (response rate of 77%).
      The prevalence of the use of vitamin and mineral supplements was 44.6%; Vitamin D
      was the most commonly used supplement. Association of supplement use with a
      higher family income and the habit of regular exercise was statistically
      significant. However, this use of supplements was not significantly associated
      with smoking or marital status. CONCLUSION: The use of supplements, particularly
      Vitamin D, by female medical students was 44.6%. The highest percentage of users
      belonged to families with higher incomes and had the habit of exercising
      regularly.

PMID- 30220847
TI  - Smoking cessation counseling: Knowledge, attitude and practices of primary
      healthcare providers at National Guard Primary Healthcare Centers, Western
      Region, Saudi Arabia.
AB  - BACKGROUND: Tobacco use is the most modifiable risk factor that increases
      mortality rates worldwide. The World Health Organization stated in 2015 that
      around six million people die each year as a result of tobacco use. Most of these
      deaths are diagnosed as premature. This study assessed the level of knowledge,
      attitude and practices of smoking cessation counseling (SCC) of primary
      healthcare providers (PHCPs) in Saudi Arabia. MATERIALS AND METHODS: A cross
      sectional study conducted from June 10, 2016 to March 31, 2017 in five Primary
      Healthcare Centers (PHC) of the Ministry of National Guard-Health Affairs,
      Jeddah, Western Region (WR). The study subjects were the staff physicians, family
      medicine doctors and dentists. Their selection was based on convenience sampling
      (N = 167, n = 130). RESULTS: More than half of the study participants (53.2%)
      were middle-aged. Most were family medicine residents (25.4%) and staff
      physicians (24.6). Fourteen physicians were smokers, only 8 (57.1%) of whom had
      tried to quit. The Internet was the main source of information on SSC (21.3%),
      followed by postgraduate studies (19.4%). The overall level of knowledge of SCC
      was poor with a mean score of 35.25 +/- 18.40; the overall level of attitude was
      good with a mean score of 76.81 +/- 8.63 and the overall level of practice was
      average, with a mean score of 55.23 +/- 21.54. There was a significant
      association between position (consultant) and knowledge (P < 0.001), attitude (P
      < 0.001) and practice (P < 0.001). CONCLUSION: PHCPs' have poor knowledge of
      counseling on the cessation of smoking and their practices are unsatisfactory
      despite their positive attitude to this role. This affects the delivery of SCC to
      the patients. Postgraduate studies, workshops and training are indeed necessary
      to help PHCPs' to understand the significance of the role they play in
      implementing SCC for patients, individuals, family and the community effectively.

PMID- 30220848
TI  - Pediatric sickle cell disease and obstructive sleep apnea: A cross-sectional
      study in a tertiary pediatric center in Saudi Arabia.
AB  - OBJECTIVE: The aim of the study was to evaluate snoring and obstructive sleep
      apnea (OSA) in Saudi children with sickle cell disease (SCD). MATERIALS AND
      METHODS: This cross-sectional study was conducted among children with SCD
      attending a hematology clinic were recruited. Demographics, clinical data, and
      sleep questionnaires were collected and overnight polysomnographies performed.
      RESULTS: Seventy children (31 of whom were females) with SCD were included in the
      study. Their median (interquartile) age was 9 (6.5, 11) years and their body mass
      index z-score was -1.2 (-2.0, -0.4). Seventy-four percent of SCD patients snored
      and 32 (46%) had evidence of OSA (obstructive apnea-hypopnea index [OAHI] >=2
      events per hour of sleep), 13 of whom had moderate OSA (OAHI >=5 and <10 events
      per hour of sleep) and 10 had severe OSA (OAHI >=10 events per hour of sleep).
      CONCLUSION: Snoring and the proportion of OSA were high in children with SCD.
      This underlines the importance of screening for OSA in all children with SCD.

PMID- 30220849
TI  - Violence towards healthcare workers: A study conducted in Abha City, Saudi
      Arabia.
AB  - BACKGROUND: Workplace violence in healthcare settings is a common, but an
      underreported problem that has been largely ignored. Violence against healthcare
      workers can have an adverse effect on their performance outcomes and thus
      influence patients' health and satisfaction. The aim of this study was to
      determine the frequency and types of violence against healthcare workers in a
      Saudi Arabian city. It was also to identify the risk factors of violence against
      healthcare workers and to investigate the possible consequences of such behavior.
      MATERIALS AND METHODS: In Abha city, there are two government hospitals and ten
      primary healthcare centers. All healthcare workers in these healthcare
      institutions including physicians, nurses, dentists, pharmacists, laboratory
      technicians or specialists, radiologists, social workers, and psychologists were
      eligible to participate in this cross-sectional study. Data were collected using
      a structured self-administered questionnaire. RESULTS: A total of 738 healthcare
      workers responded (92% response rate). The mean age was 31 +/- 7.7 years (range
      21-60) and the majority (64.9%) were females and 69.4% were Saudis. More than
      half (57.5%) had experienced some workplace violence at least once. Verbal
      assaults and slaps were the most common form of workplace-related violence (58%).
      CONCLUSIONS: Violence against healthcare workers in Abha city is more common,
      especially against nurses. The reasons need to be explored in order to set and
      develop policies, regulations and interventions to prevent violence against
      workers.

PMID- 30220850
TI  - Knowledge, attitude, and performance of primary healthcare physicians in Aseer
      Region, Saudi Arabia about attention deficit hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is one of the most
      common psychiatric disorders. This study aimed to assess the knowledge, attitude,
      and practice of primary health-care (PHC) physicians on diagnosis and management
      of ADHD. MATERIALS AND METHODS: This was a cross-sectional study included 340 PHC
      physicians in Aseer Region, Saudi Arabia. A self-administered questionnaire was
      used to collect data on personal characteristics, knowledge, attitude, and
      practice of the diagnosis and management of ADHD. RESULTS: Nearly 47.6% of the
      PHC physicians were aged <30 years, 60.3% were male, 79.1% were Saudi nationals,
      and 84.1% had completed MBBS. Only 13.2% had attended continuing medical
      education courses on ADHD, 63.2% had read about ADHD; Internet was the main
      source of information (30.7%). Participants' attitude toward ADHD was mainly
      positive, while 32.1% had poor knowledge and 17.6% had diagnosed ADHD cases in
      the last year, but 73.3% had referred the diagnosed cases to specialists.
      Participants' knowledge differed significantly according to their age, gender,
      and nationality. CONCLUSIONS: PHC physicians' knowledge about ADHD was
      suboptimal, but they had a positive attitude toward their role with regard to
      ADHD. PHC physicians should focus on the clinical and diagnostic aspects of ADHD.
      Awareness and interest of undergraduate medical students and newly graduated
      physicians in ADHD should be raised. The Ministry of Health should encourage
      attendance at extracurricular courses and workshops.

PMID- 30220851
TI  - Correlates of physical disability in the elderly population of Rural North India
      (Haryana).
AB  - BACKGROUND: With the increase in life expectancy, the number of older persons is
      constantly rising. Disability rates for elderly people are also on the rise with
      an increase in the burden of chronic diseases depriving them of independence and
      the performance of activities of daily living. The study aimed to estimate the
      prevalence of physical disability and determine its correlates among elderly
      population of rural Haryana. MATERIALS AND METHODS: A community-based cross
      sectional study was conducted among 322 elderly participants aged 60 years and
      above in the rural area of Haryana, India. Data pertaining to sociodemographic
      profile, self-reported chronic diseases/ailments, and disability assessment by
      means of Barthel and Katz index of activities of daily living was collected and
      analyzed. RESULTS: Overall, 21.4% and 18% elderly people had some form of
      disability according to the Barthel index and Katz index, respectively. With
      aging, disability increased and 52.5% of the elderly aged 75 years and above were
      found to have disability according to the Barthel's index. Females (P = 0.014),
      those who were currently not married (P = 0.001), currently unemployed (P =
      0.001), and those with chronic diseases/ailments (P = 0.002), had significantly
      higher disability rates. Binary logistic regression analysis revealed age 75
      years and above, current unemployment, and the presence of three or more chronic
      diseases/ailments as significant factors related to physical disability.
      CONCLUSION: Disability is associated with increasing age and an increase in the
      burden of chronic health ailments in the elderly. Consequently, there is the need
      to prioritize preventive, promotive, curative, and rehabilitative services for
      the geriatric population.

PMID- 30220852
TI  - Hoarseness among school teachers: A cross-sectional study from Dammam.
AB  - BACKGROUND: Voice disorders are known to be a serious occupational hazard for
      teachers. Compared to the general population, teachers have a greater risk of
      developing hoarseness of voice. The prevalence of voice disorders in teachers is
      20%-50%. To the best of our knowledge, there has been no study in Saudi Arabia
      (SA) on the prevalence of hoarseness in teachers. MATERIALS AND METHODS: A cross
      sectional survey was conducted in 13 randomly selected schools at different
      levels of education in Khobar, SA, between February 2016 and March 2016. Data
      collected included demographic data, comorbidity, smoking, school type,
      laryngopharyngeal reflux, hearing problems, common cold, family history, number
      of students, and stress. The study included teachers who were actively teaching.
      Teachers with laryngeal cancer and those who were not actively teaching as well
      as those who were on sick leave were all excluded from the study. Data were
      analyzed using SPSS version 20. RESULTS: Out of 400 surveys distributed, 187
      teachers responded; mean age of teachers was 42.5 years and 55.1% were females.
      The percentage of teachers who subjectively complained of hoarseness was 27%;
      teachers in public schools had a higher prevalence of hoarseness than teachers in
      private schools. The greater the number of students per class, the more likely it
      was for the teacher to develop hoarseness (P = 0.038). The factors statistically
      significantly associated with hoarseness included smoking, acid reflux, family
      history of hoarseness, and work-related stress. CONCLUSION: Prevalence of
      hoarseness in teachers is high owing to a combination of multiple associated
      factors, many of which can be controlled.

PMID- 30220853
TI  - Bullying among medical and nonmedical students at a university in Eastern Saudi
      Arabia.
AB  - BACKGROUND: Many medical students, junior doctors, and other health-care
      professionals have been affected by the negative experience of bullying. Research
      is scarce on bullying experienced by medical and nonmedical students in Saudi
      Arabia unlike what is found in Western countries. It is unclear whether being a
      nonmedical student modifies the risk of being bullied. MATERIALS AND METHODS: A
      cross-sectional study included 400 university students using convenient sampling.
      The sample comprised 295 students who responded and were stratified into medical
      (n = 176) and nonmedical (n = 119) groups. Statistical Package for the Social
      Sciences (SPSS) version 22.0 was used to analyze our data. Normality was measured
      using the Kolmogorov-Smirnov test. Statistical significance was tested using chi
      square test for categorical variables, and t-test for continuous variables.
      RESULTS: Almost half of the respondents were found to have experienced some
      bullying, victimization, or other harassment during their medical education. The
      most common forms of bullying were verbal abuse and undue pressure to produce
      work (43.8%; n = 77). Nonmedical students experienced more bullying than medical
      students and were more likely to be female, single, and younger in age. The
      number of medical students subjected to sexual harassment (1.7%; n = 3) was
      higher than nonmedical students (0.8%; n = 1). Physical violence was more towards
      nonmedical (4.2%; n = 5) than medical students (1.1%, n = 2). The rates of
      bullying continue to be associated with anxiety and depression. CONCLUSIONS: Our
      data suggest similar bullying rates in the developed world but higher than
      previously reported in a Saudi study. Bullying or harassment affects both medical
      and nonmedical students and is associated with high levels of anxiety and
      depression.

PMID- 30220854
TI  - Recurrent extensive plunging ranula: A rare case.
AB  - Plunging ranula (PR) is a cystic mass presenting on the lateral side of the neck
      with or without a history of the usual presentation of an intraoral lesion. "PR"
      is recognized as an uncommon lesion that has been found predominantly in the
      third decade of life mostly in males. However, the exact prevalence of "PR" is
      not yet known. We report a rare case of an extensive PR that reached the
      parapharyngeal space in a 17-year-old Saudi female. The diagnosis was made when
      she presented to the ENT clinic with swellings in the right submandibular and
      right floor of the mouth. The diagnosis of "PR" with the absence of an oral
      lesion is very challenging and requires a detailed history, clinical examination,
      and radiological imaging. Different modalities of treatment have been discussed.
      However, the excision of ranula and the sublingual gland is the most effective
      way of management.

PMID- 30220855
TI  - A comment on a study by Yazdanpanahi et al. (2018).

PMID- 30220856
TI  - Author's reply.

PMID- 30220857
TI  - Falls among elderly and its relation with their health problems and surrounding
      environmental factors in Riyadh.

PMID- 30220858
TI  - Erratum: Mobile phone use while driving and the risk of collision: A study among
      preparatory year students at King Saud University, Riyadh, Saudi Arabia.
AB  - [This corrects the article on p. 102 in vol. 25, PMID: 29922110.].

PMID- 30220859
TI  - The reduction of summer sulfate and switch from summertime to wintertime PM2.5
      concentration maxima in the United States.
AB  - Exposure to particulate matter air pollution with a nominal mean aerodynamic
      diameter less than or equal to 2.5 MUm (PM2.5) has been associated with health
      effects including cardiovascular disease and death. Here, we add to the
      understanding of urban and rural PM2.5 concentrations over large spatial and
      temporal scales in recent years. We used high-quality, publicly-available air
      quality monitoring data to evaluate PM2.5 concentration patterns and changes
      during the years 2000-2015. Compiling and averaging measurements collected across
      the U.S. revealed that PM2.5 concentrations from urban sites experienced seasonal
      maxima in both winter and summer. Within each year from 2000 to 2008, the maxima
      of urban summer peaks were greater than winter peaks. However, from 2012 to 2015,
      the maxima of urban summertime PM2.5 peaks were smaller than the urban wintertime
      PM2.5 maxima, due to a decrease in the magnitude of summertime maxima with no
      corresponding decrease in the magnitude of winter maxima. PM2.5 measurements at
      rural sites displayed summer peaks with magnitudes relatively similar to those of
      urban sites, and negligible to no winter peaks through the time period analyzed.
      Seasonal variations of urban and rural PM2.5 sulfate, PM2.5 nitrate, and PM2.5
      organic carbon (OC) were also assessed. Summer peaks in PM2.5 sulfate decreased
      dramatically between 2000 and 2015, whereas seasonal PM2.5 OC and winter PM2.5
      nitrate concentration maxima remained fairly consistent. These findings
      demonstrate that PM2.5 concentrations, especially those occurring in the
      summertime, have declined in the U.S. from 2000 to 2015. In addition, reduction
      strategies targeting sulfate have been successful and the decrease in PM2.5
      sulfate contributed to the decline in total PM2.5.

PMID- 30220860
TI  - Distinguishing welfare state reform and income redistribution. A two-dimensional
      approach to the Dutch voter space on economic issues.
AB  - There is growing evidence that voter and party positions on economic items do not
      conform to a left-right dimension. This article proposes that in Northern
      Eurozone states voter policy positions on economic issues are characterized by
      two dimensions: A redistribution dimension that consists out of views on income
      equality and a reform dimension that divides those who favour reform of the
      welfare state to ensure its long-term sustainability and those who oppose such
      reforms because they would hurt those who need the welfare state now. It examines
      to what extent voters positions on economic issues conform this two-dimensional
      pattern, employing the 2012 Dutch Election Survey; to what extent positions on
      these dimensions reflects voters' attitudes on other issues and demographic
      characteristics; and to what extent these two dimensions help to understand
      voting behaviour. It shows that indeed a multidimensional approach to economic
      issues is justified; that voters who oppose reforms are characterized by higher
      levels of Euroscepticism; and that this reform dimension helps to understand
      voting behaviour, in particular preferences for the socialist, social-democratic
      and social-liberal party.

PMID- 30220862
TI  - Optimized multi-shot imaging inspection design.
AB  - The inspection of complex-shaped components, such as those enabled by additive
      manufacturing, is a major challenge in industrial quality assurance. A frequently
      adopted approach to volumetric non-destructive evaluation is X-ray computed
      tomography, but this has major drawbacks. Two-dimensional radiography can
      overcome some of these problems, but does not generally provide an inspection
      that is as capable. Moreover, designing a detailed inspection for a complex
      shaped component is a labour-intensive task, requiring significant expert input.
      In response, a computational framework for optimizing the data acquisition for an
      image-based inspection modality has been devised. The initial objective is to
      advance the capabilities of radiography, but the algorithm is, in principle, also
      applicable to alternative types of imaging. The algorithm exploits available
      prior information about the inspection and simulations of the inspection modality
      to allow the determination of the optimal inspection configuration, including
      specifically component poses with respect to the imaging system. As an
      intermediate output, spatial maps of inspection performance are computed, for
      understanding spatially varying limits of detection. Key areas of innovation
      concern the defect detectability evaluation for arbitrarily complex indications
      and the creation of an application-specific optimization algorithm. Initial
      trials of the algorithm are presented, with good results.

PMID- 30220861
TI  - Differences in Behavior, Time, Location, and Built Environment between
      Objectively Measured Utilitarian and Recreational Walking.
AB  - Objectives: Utilitarian and recreational walking both contribute to physical
      activity. Yet walking for these two purposes may be different behaviors. We
      sought to provide operational definitions of utilitarian and recreational walking
      and to objectively measure their behavioral, spatial, and temporal differences in
      order to inform transportation and public health policies and interventions.
      Methods: Data were collected 2008-2009 from 651 Seattle-King County residents,
      wearing an accelerometer and a GPS unit, and filling-in a travel diary for 7
      days. Walking activity bouts were classified as utilitarian or recreational based
      on whether walking had a destination or not. Differences between the two walking
      purposes were analyzed, adjusting for the nested structure of walking activity
      within participants. Results: Of the 4,905 observed walking bouts, 87.4% were
      utilitarian and 12.6% recreational walking. Utilitarian walking bouts were 45%
      shorter in duration (-12.1 min) and 9% faster in speed (+0.3km/h) than
      recreational walking bouts. Recreational walking occurred more frequently in the
      home neighborhood and was not associated with recreational land uses. Utilitarian
      walking occurred in areas having higher residential, employment, and street
      density, lower residential property value, higher area percentage of mixed-use
      neighborhood destinations, lower percentage of parks/trails, and lower average
      topographic slope than recreational walking. Conclusion: Utilitarian and
      recreational walking are substantially different in terms of frequency, speed,
      duration, location, and related built environment. Policies that promote walking
      should adopt type-specific strategies. The high occurrence of recreational
      walking near home highlights the importance of the home neighborhood for this
      activity.

PMID- 30220863
TI  - Interfacial load transfer mechanisms in carbon nanotube-polymer nanocomposites.
AB  - Carbon nanotubes (CNTs) are highly promising for strength reinforcement in
      polymer nanocomposites, but conflicting interfacial properties have been reported
      by single nanotube pull-out experiments. Here, we report the interfacial load
      transfer mechanisms during pull-out of CNTs from PMMA matrices, using massively-
      parallel molecular dynamics simulations. We show that the pull-out forces
      associated with non-bonded interactions between CNT and PMMA are generally small,
      and are weakly-dependent on the embedment length of the nanotube. These pull-out
      forces do not significantly increase with the presence of Stone Wales or vacancy
      defects along the nanotube. In contrast, low-density distribution of cross-links
      along the CNT-PMMA interface increases the pull-out forces by an order of
      magnitude. At each cross-linked site, mechanical unfolding and pull-out of single
      or pair polymer chain(s) attached to the individual cross-link bonds result in
      substantial interfacial strengthening and toughening, while contributing to
      interfacial slip between CNT and PMMA. Our interfacial shear-slip model shows
      that the interfacial loads are evenly-distributed among the finite number of
      cross-link bonds at low cross-link densities or for nanotubes with short
      embedment lengths. At higher cross-link densities or for nanotubes with longer
      embedment lengths, a no-slip zone now develops where shear-lag effects become
      important. Implications of these results, in the context of recent nanotube pull
      out experiments, are discussed.

PMID- 30220864
TI  - Radon signals in geological (natural) geogas and in a simultaneous enhanced
      confined mode simulation experiment.
AB  - An enhanced confined mode (ECM) radon simulation experiment, tested in the
      laboratory in Jerusalem, was relocated to a subsurface geophysical observatory
      located 400 km apart, at a depth of 150 m and with a stable temperature. Five
      gamma sensors are placed around the ECM canister and lead shielding minimizes the
      influence of natural local gamma radiation. Simultaneous measurement of the
      geological radon and from radon in the ECM system indicates that the temporal
      variation of gamma radiation from radon in the ECM system contains annual, multi
      day and daily signals, that correspond to signals in the local geological radon.
      This implies that a common external driver influences the radiation pattern of
      the geological radon and from radon inside the ECM canister. Once activated at
      BGO the typical variation pattern of the experimental system occurring in the
      laboratory changed to that occurring at the observatory. This is interpreted to
      indicate that the overall style of the temporal patterns of radiation from radon
      is site dependent. The outcome of this investigation conforms and further
      substantiates the recent suggestion that a component in solar radiation is
      driving the annual and daily periodic components in the variation of radon. New
      geophysical research potential is indicated.

PMID- 30220865
TI  - Analytical estimation of non-local deformation-mediated magneto-electric coupling
      in soft composites.
AB  - For a long time, the search for magneto-electric materials concentrated on multi
      ferroics and hard-matter composites. By contrast, rather recently the
      exploitation of strain-mediated magneto-electric (ME) coupling in soft composites
      was proposed. The basic idea behind this approach is to combine the magneto- and
      electro-mechanical responses of composites consisting of a soft matrix carrying
      magnetic inclusions. Despite that such composites are straightforward to
      manufacture and have cheap constituents, they did not gain much attention up to
      now. In this contribution, we demonstrate that ME coupling induced by finite
      deformations could be of significant magnitude. Our approach relies on shape
      effects as a special non-local phenomenon in magneto- and electro-elasticity.
      Based on that we characterize an up to now overlooked ME coupling mechanism which
      purely relies on these shape effects in soft-matter-based magnetic and electric
      media. While soft magnetic media are commonly realized as composites, the
      coupling effect to be highlighted exists independently of the origin of a body's
      magnetic and electric properties. We show that the magnitude of the effect is
      indeed significant and, among ellipsoidal bodies, most pronounced for those of
      spherical to moderately prolate shape. Finite-element simulations are performed
      to assess the quality of the analytical predictions.

PMID- 30220866
TI  - Wrinkling in engineering fabrics: a comparison between two different
      comprehensive modelling approaches.
AB  - We consider two 'comprehensive' modelling approaches for engineering fabrics. We
      distinguish the two approaches using the terms 'semi-discrete' and 'continuum',
      reflecting their natures. We demonstrate a fitting procedure, used to identify
      the constitutive parameters of the continuum model from predictions of the semi
      discrete model, the parameters of which are in turn fitted to experimental data.
      We, then, check the effectiveness of the continuum model by verifying the
      correspondence between semi-discrete and continuum model predictions using test
      cases not previously used in the identification process. Predictions of both
      modelling approaches are compared against full-field experimental kinematic data,
      obtained using stereoscopic digital image correlation techniques, and also with
      measured force data. Being a reduced order model and being implemented in an
      implicit rather than an explicit finite-element code, the continuum model
      requires significantly less computational power than the semi-discrete model and
      could therefore be used to more efficiently explore the mechanical response of
      engineering fabrics.

PMID- 30220867
TI  - Accessory parameters in conformal mapping: exploiting the isomonodromic tau
      function for Painleve VI.
AB  - We present a novel method to solve the accessory parameter problem arising in
      constructing conformal maps from a canonical simply connected planar region to
      the interior of a circular arc quadrilateral. The Schwarz-Christoffel accessory
      parameter problem, relevant when all sides have zero curvature, is also captured
      within our approach. The method exploits the isomonodromic tau function
      associated with the Painleve VI equation. Recently, these tau functions have been
      shown to be related to certain correlation functions in conformal field theory
      and asymptotic expansions have been given in terms of tuples of the Young
      diagrams. After showing how to extract the monodromy data associated with the
      target domain, we show how a numerical approach based on the known asymptotic
      expansions can be used to solve the conformal mapping accessory parameter
      problem. The viability of this new method is demonstrated by explicit examples
      and we discuss its extension to circular arc polygons with more than four sides.

PMID- 30220868
TI  - Neutron reflectometry with the Multi-Blade 10B-based detector.
AB  - The Multi-Blade is a boron-10-based gaseous detector developed for neutron
      reflectometry instruments at the European Spallation Source in Sweden. The main
      challenges for neutron reflectometry detectors are the instantaneous counting
      rate and spatial resolution. The Multi-Blade has been tested on the CRISP
      reflectometer at the ISIS Neutron and Muon Source in the UK. A campaign of
      scientific measurements has been performed to study the Multi-Blade response in
      real instrumental conditions. The results of these tests are discussed in this
      paper.

PMID- 30220869
TI  - From arteries to boreholes: transient response of a poroelastic cylinder to fluid
      injection.
AB  - The radially outward flow of fluid through a porous medium occurs in many
      practical problems, from transport across vascular walls to the pressurization of
      boreholes in the subsurface. When the driving pressure is non-negligible relative
      to the stiffness of the solid structure, the poromechanical coupling between the
      fluid and the solid can control both the steady state and the transient mechanics
      of the system. Very large pressures or very soft materials lead to large
      deformations of the solid skeleton, which introduce kinematic and constitutive
      nonlinearity that can have a non-trivial impact on these mechanics. Here, we
      study the transient response of a poroelastic cylinder to sudden fluid injection.
      We consider the impacts of kinematic and constitutive nonlinearity, both
      separately and in combination, and we highlight the central role of driving
      method in the evolution of the response. We show that the various facets of
      nonlinearity may either accelerate or decelerate the transient response relative
      to linear poroelasticity, depending on the boundary conditions and the initial
      geometry, and that an imposed fluid pressure leads to a much faster response than
      an imposed fluid flux.

PMID- 30220870
TI  - On the geometrically exact low-order modelling of a flexible beam: formulation
      and numerical tests.
AB  - This paper proposes a low-order geometrically exact flexible beam formulation
      based on the utilization of generic beam shape functions to approximate
      distributed kinematic properties of the deformed structure. The proposed
      nonlinear beam shapes approach is in contrast to the majority of geometrically
      nonlinear treatments in the literature in which element-based-and hence high
      order-discretizations are adopted. The kinematic quantities approximated
      specifically pertain to shear and extensional gradients as well as local
      orientation parameters based on an arbitrary set of globally referenced attitude
      parameters. In developing the dynamic equations of motion, an Euler angle
      parametrization is selected as it is found to yield fast computational
      performance. The resulting dynamic formulation is closed using an example shape
      function set satisfying the single generic kinematic constraint. The formulation
      is demonstrated via its application to the modelling of a series of static and
      dynamic test cases of both simple and non-prismatic structures; the simulated
      results are verified using MSC Nastran and an element-based intrinsic beam
      formulation. Through these examples, it is shown that the nonlinear beam shapes
      approach is able to accurately capture the beam behaviour with a very minimal
      number of system states.

PMID- 30220871
TI  - Retraction of 'Providing sustainable catalytic solutions for a rapidly changing
      world'.
AB  - [This retracts the article DOI: 10.1098/rspa.2018.0414.].

PMID- 30220872
TI  - Perceived time adequacy improves daily well-being: day-to-day linkages and the
      effects of a workplace intervention.
AB  - Workplace interventions may change how employed parents experience family and
      personal time. This study examined the day-to-day linkages between time resources
      (assessed by time use and perceived time adequacy for parenting, partner, and
      personal roles) and daily well-being and tested whether a workplace intervention
      enhanced the linkages. Participants were employed, partnered parents in the
      information technology division of a large US firm and who provided eight-day
      diary data at two times (N = 90). Multilevel modeling revealed that, on days when
      parents perceived lower time adequacy than usual for the three roles, they
      reported less positive affect, more negative affect, and more physical symptoms,
      independent of time spent in the roles. Moreover, a workplace intervention
      designed to give employees more temporal flexibility and support for family
      responsibilities increased daily time spent with the focal child and increased
      perceived time adequacy for exercise. The intervention also decreased negative
      affect and physical symptoms for parents who spent more time with child and
      partner than the sample average. Our results highlight the importance of
      perceived time adequacy in daily well-being and suggest that workplace support
      can enhance perceived time adequacy for self and the experience of family time.

PMID- 30220873
TI  - Implications of parents' work travel on youth adjustment.
AB  - Guided by ecological, work-family spillover and crossover frameworks, this study
      examined mechanisms linking parental work travel (i.e., nights per year) to youth
      adjustment (i.e., externalizing and internalizing behaviours) through youth's
      perceptions of parenting (i.e., knowledge, solicitation) with traveller and youth
      gender as moderators in a sample of 78 children in 44 two-parent families
      residing in the United States. The findings from multilevel analyses suggested
      that mothers' travel nights predicted lower levels of maternal knowledge, with
      variation by traveller and youth gender. Mothers' and fathers' work travel and
      perceived parenting were predictors of youth's externalizing behaviours, whereas
      only fathers' work travel and perceived parenting were predictors of youth's
      internalizing behaviours. Tests of indirect effects indicated that maternal work
      travel linked to youth's externalizing behaviours through youth's perceptions of
      maternal knowledge. These findings add to our limited understanding of work
      family issues for parents who have the unique work demand of frequently
      travelling.

PMID- 30220874
TI  - Towards clinically feasible relaxation-diffusion correlation MRI using MADCO.
AB  - Multidimensional relaxation-diffusion correlation (REDCO) NMR is an assumption
      free method that measures how water is distributed within materials. Although
      highly informative, REDCO had never been used in clinical MRI applications
      because of the large amount of data it requires, leading to infeasible scan
      times. A recently suggested novel experimental design and processing framework,
      marginal distributions constrained optimization (MADCO), was used here to
      accelerate and improve the reconstruction of such MRI correlations. MADCO uses
      the 1D marginal distributions as a priori information, which provide powerful
      constraints when 2D spectra are reconstructed, while their estimation requires an
      order of magnitude less data than conventional 2D approaches. In this work we
      experimentally examined the impact the complexity of the correlation distribution
      has on the accuracy and robustness of the estimates. MADCO and a conventional
      method were compared using two T1-D phantoms that differ in the proximity of
      their peaks, leading to a relatively simple case as opposed to a more challenging
      one. The phantoms were used to vet the achievable data compression using MADCO
      under these conditions. MADCO required ~43 and ~30 less data than the
      conventional approach for the simple and complex spectra, respectively, making it
      potentially feasible for preclinical and even clinical applications.

PMID- 30220875
TI  - Where Vectors Collide: The Importance of Mechanisms Shaping the Realized Niche
      for Modeling Ranges of Invasive Aedes Mosquitoes.
AB  - The vector mosquitoes Aedes aegypti (L.), native to Africa, and Aedes albopictus
      (Skuse), native to Asia, are widespread invasives whose spatial distributions
      frequently overlap. Predictive models of their distributions are typically
      correlative rather than mechanistic, and based on only abiotic variables
      describing putative environmental requirements despite extensive evidence of
      competitive interactions leading to displacements. Here we review putative roles
      of competition contributing to distribution changes where the two species meet.
      The strongest evidence for competitive displacements comes from multiple examples
      of habitat segregation where the two species co-occur and massive reductions in
      the range and abundance of A. aegypti attributable to A. albopictus invasions in
      the southeastern U.S.A. and Bermuda (U.K). We summarize evidence to support the
      primacy of asymmetric reproductive interference, or satyrization, and larval
      resource competition, both favoring A. albopictus, as displacement mechanisms.
      Where evidence of satyrization or interspecific resource competition is weak,
      differences in local environments or alternative ecologies or behaviors of these
      Aedes spp. may explain local variation in the outcomes of invasions. Predictive
      distribution modeling for both these major disease vectors needs to incorporate
      species interactions between them as an important process that is likely to limit
      their realized niches and future distributions. Experimental tests of
      satyrization and resource competition are needed across the broad ranges of these
      species, as are models that incorporate both reproductive interference and
      resource competition to evaluate interaction strengths and mechanisms. These
      vectors exemplify how fundamental principles of community ecology may influence
      distributions of invasive species.

PMID- 30220876
TI  - RhIII-Catalyzed Synthesis of Isoquinolones and 2-Pyridones via Annulation of N
      Methoxyamides and Nitroalkenes.
AB  - The Rh(III)-catalyzed synthesis of 4-substituted isoquinolones and 2-pyridones by
      the annulation of N-methoxyamides and nitroalkenes has been developed. Both
      aliphatic and aromatic nitroalkenes were effective inputs. Annulations also
      proceeded for aromatic, alkenyl, and heteroaromatic C-H bond starting materials.
      Moreover, benzoic acid provided a novel nitrodihydroisocoumarin. The structure
      and relative stereochemistry of this compound, which is an oil at room
      temperature, was determined unambiguously by single crystal X-ray diffraction of
      its inclusion complex with a hydrogen-bonded host framework.

PMID- 30220878
TI  - Bread and butter or bread and circuses? Politicisation and the European
      Commission in the European Semester.
AB  - Does domestic contestation of European Union legitimacy affect the behaviour of
      the European Commission as an economic and fiscal supervisor? We draw on theories
      of bureaucratic responsiveness and employ multilevel and topic modelling to
      examine the extent to which the politicisation of European integration affects
      the outputs of the European Semester: the Country-Specific Recommendations. We
      develop two competing sets of hypotheses and test these on an original large-N
      data set on Commission behaviour with observations covering the period 2011-2017.
      We detect a twofold effect on the Commission's recommendations: member states
      that experience greater politicisation receive recommendations that are larger in
      scope but whose substance is less oriented towards social investment. We argue
      that this effect is best explained as an outcome of the Commission's
      institutional risk management strategy of regulatory 'entrenchment'. The
      supranational agent issues additional recommendations while simultaneously
      entrenching on a stronger mandate substantively, which allows it to maintain its
      regulatory reputation and signal regulatory resolve to observing audiences.

PMID- 30220877
TI  - Double and triple inclusive gluon production at mid rapidity: quantum
      interference in p-A scattering.
AB  - We compute double and triple inclusive gluon production in p-A scattering beyond
      the so-called "glasma graph" approximation. We consider quantum interference
      effects and identify in this general setup the terms responsible for the gluon
      HBT and initial wave function Bose enhancement which lead to correlations in
      particle production. Both of these terms originate from the factorizable part of
      the quadrupole and sextupole terms in the production cross section. We also show
      that the target Bose enhancement in this regime is suppressed at large number of
      colors.

PMID- 30220880
TI  - Development of an epiphyte indicator of nutrient enrichment: a critical
      evaluation of observational and experimental studies.
AB  - An extensive review of the literature describing epiphytes on submerged aquatic
      vegetation (SAV), especially seagrasses, was conducted in order to evaluate the
      evidence for response of epiphyte metrics to increased nutrients. Evidence from
      field observational studies, together with laboratory and field mesocosm
      experiments, was assembled from the literature and evaluated for a hypothesized
      positive response to nutrient addition. There was general consistency in the
      results to confirm that elevated nutrients tended to increase the load of
      epiphytes on the surface of SAV, in the absence of other limiting factors. In
      spite of multiple sources of uncontrolled variation, positive relationships of
      epiphyte load to nutrient concentration or load (either nitrogen or phosphorus)
      often were observed along strong anthropogenic or natural nutrient gradients in
      coastal regions. Such response patterns may only be evident for parts of the
      year. Results from both mesocosm and field experiments also generally support the
      increase of epiphytes with increased nutrients, although outcomes from field
      experiments tended to be more variable. Relatively few studies with nutrient
      addition in mesocosms have been done with tropical or subtropical species, and
      more such controlled experiments would be helpful. Experimental duration
      influenced results, with more positive responses of epiphytes to nutrients at
      shorter durations in mesocosm experiments versus more positive responses at
      longer durations in field experiments. In the field, response of epiphyte biomass
      to nutrient additions was independent of climate zone. Mesograzer activity was a
      critical covariate for epiphyte response under experimental nutrient elevation,
      but the epiphyte response was highly dependent on factors such as grazer identity
      and density, as well as nutrient and ambient light levels. The balance of
      evidence suggests that epiphytes on SAV will be a useful indicator of persistent
      nutrient enhancement in many situations. Careful selection of appropriate
      temporal and spatial constraints for data collection, and concurrent evaluation
      of confounding factors will help increase the signal to noise ratio for this
      indicator.

PMID- 30220879
TI  - HIV testing and access to HIV medical care among people who inject drugs and
      their intimate partners in Kazakhstan.
AB  - Background: Growing rates of HIV and high rates of injection drug use in
      Kazakhstan call for examining access to testing and treatment among people who
      inject drugs and their intimate partners. Objectives: We examine how access to
      health and drug treatment services as well as risk environment factors are
      associated with ever being tested for HIV and ever receiving any general HIV
      medical care among 728 male and female intimate partners where at least one
      partner injects drugs. Methods: Multivariate random effects logistic regression
      with random effects for couple were conducted to examine associations between
      access to health and drug treatment services, risk environment factors, and HIV
      testing and HIV medical care outcomes. Results: Analyses indicate that accessing
      needle exchange services and having a regular physician were associated both with
      access to HIV testing and HIV medical care. Receiving drug treatment was
      associated with accessing HIV testing but not HIV medical care. Being arrested
      and charged with a criminal offense was also associated with accessing HIV
      testing but not HIV medical care. Conclusions/Importance: Study findings
      highlight the need for increased scale-up of HIV testing efforts, as well as
      integrated HIV treatment and care in Kazakhstan.

PMID- 30220881
TI  - "I see myself as part of the team" - family caregivers' contribution to safety in
      advanced home care.
AB  - Background: The use of medical technology and the various contributing and
      interdepending human factors in home care have implications for patient safety.
      Although family caregivers are often involved in the provision of advanced home
      care, there is little research on their contribution to safety. The study aims to
      explore family caregivers in Home Mechanical Ventilation (HMV) safety experiences
      and how safety is perceived by them in this context. Furthermore, it seeks to
      understand how family caregivers contribute to the patients' and their own safety
      in HMV and what kind of support they expect from their health care team. Methods:
      An explorative, qualitative study was applied using elements from grounded theory
      methodology. Data were collected through individual interviews with 15 family
      caregivers to patients receiving HMV in two regions in Germany. The audiotaped
      interviews were then subject to thematic analysis. Results: The findings shows
      that family caregivers contribute to safety in HMV by trying to foster mutual
      information sharing about the patient and his/her situation, coordinating
      informally health care services and undertaking compensation of shortcomings in
      HMV. Conclusion: Consequently, family caregivers take on considerable
      responsibility for patient safety in advanced home care by being actively and
      constantly committed to safety work.Nurses working in this setting should be
      clinically and technically skilled and focus on building partnership relations
      with family caregivers. This especially encompasses negotiation about their role
      in care and patient safety. Support and education should be offered if needed.
      Only skilled nurses, who can provide safe care and who can handle critical
      situations should be appointed to HMV. They should also serve as professional
      care coordinators and provide educational interventions to strengthen family
      caregivers' competence.

PMID- 30220882
TI  - BC094916 suppressed SP 2/0 xenograft tumor by down-regulating Creb1 and Bcl2
      transcription.
AB  - Background: Both multiple myeloma (MM) and systemic lupus erythematosus (SLE) are
      associated with abnormal production of plasma cells, although their pathological
      mechanism of each disease is different. The main characteristic of both diseases
      is uncontrolled differentiation of B cells into plasmablast/plasma cells. Despite
      continuous research on prognostic factors and the introduction of new agents for
      MM and SLE, treatments still do not exist for controlling plasmablast/plasma
      cells. Thus, it is necessary to identify novel therapeutic targets of
      plasmablast/plasma cells. Because of its plasmablast-like characteristics, the
      mus musculus myeloma SP 2/0 cell line was used in this study to test the effect
      of a novel therapeutic agent (BC094916 overexpression) on plasmablast/plasma
      cells. Methods: We first determined gene expression profiles of plasma cells
      using Affymetrix microarrays and RNA-sequencing. The effect of BC094916 on SP 2/0
      cell proliferation, cell cycle, and apoptosis was determined by CCK8 and
      fluorescence-activated cell sorting. The SP 2/0 xenograft mouse model was used to
      assess the impact of BC094916 on tumor progression. The luciferase reporter
      system was used to evaluate the effect of BC094916 on Creb1 and Bcl2
      transcription. Results: We found that BC094916 mRNA was decreased in plasma
      cells. The mouse myeloma cell line SP 2/0 expressed low levels of BC094916 mRNA,
      whereas BC094916 overexpression suppressed SP 2/0 cell proliferation by inducing
      apoptosis. BC094916 overexpression suppressed tumor progression in the SP 2/0
      xenograft mouse model. We also found that BC094916 mediate apoptosis by
      suppressing transcription of the Creb1 and Bcl2 genes, which promote the
      transcription of eukaryotic translation initiation and elongation factor genes.
      Conclusions: BC094916 overexpression suppressed Creb1 and Bcl2 transcription to
      induce cell apoptosis, which suppressed SP 2/0 proliferation and xenograft tumor
      progression. Thus, BC094916 overexpression may be a potential therapeutic agent
      for treatment of MM and autoimmune diseases such as SLE.

PMID- 30220884
TI  - Push or Carry? Pragmatic Opportunities for Language Development in Strollers vs.
      Backpacks.
AB  - Strollers and backpacks are employed early, frequently and throughout the first
      year, with parents overwhelmingly using strollers. However, because these
      transport modalities put infants in different proximities to caregivers,
      postures, and states of alertness, their use may translate to different
      opportunities that are of developmental consequence, particularly with regard to
      language. We used GoPro technology in a within subjects counter-balanced design
      to measure dyadic vocalizations in strollers and backpacks with 7-to-11-month-old
      infants. Parent-infant dyads (N=36), who regularly used both transport modes took
      two 8-minute walks in their own neighborhoods using their own carriers while
      wearing lightweight head-mounted GoPros. There was significantly more parent
      speech, infant vocalizations, dyadic conversations and infant-initiated speech in
      backpacks, as well as more head motion consistent with visual scanning by
      infants. Backpacks appear to be a practical way to encourage more engaging,
      language-enriched developmental opportunities in the critical first year.

PMID- 30220885
TI  - Performance of IMERG as a Function of Spatiotemporal Scale.
AB  - The Integrated Multi-satellitE Retrievals for GPM (IMERG), a global high
      resolution gridded precipitation data set, will enable a wide range of
      applications, ranging from studies on precipitation characteristics to
      applications in hydrology to evaluation of weather and climate models. These
      applications focus on different spatial and temporal scale and thus average the
      precipitation estimates to coarser resolutions. Such a modification of scale will
      impact the reliability of IMERG. In this study, the performance of the Final run
      of MERG is evaluated against ground-based measurements as a function of
      increasing spatial resolution (from 0.1 degrees  to 2.5 ) and accumulation
      periods (from 0.5 h to 24 h) over a region in the southeastern US. For ground
      reference, a product derived from the Multi-Radar/Multi-Sensor suite, a radar-
      and gauge-based operational precipitation dataset, is used. The TRMM Multi
      satellite Precipitation Analysis (TMPA) is also included as a benchmark. In
      general, both IMERG and TMPA improve when scaled up to larger areas and longer
      time periods, with better identification of rain occurrences and consistent
      improvements in systematic and random errors of rain rates. Between the two
      satellite estimates, IMERG is slightly better than TMPA most of the time. These
      results will inform users on the reliability of IMERG over the scales relevant to
      their studies.

PMID- 30220886
TI  - Real-time Simutaneous Separation and Detection of Chemicals using Integrated
      Micro Column and Surface Plasmon Resonance Imaging Micro-GC.
AB  - An integrated and miniaturized Micro-Gas Chromatography with real-time imaging
      capability for simultaneous chemical separation and detection was developed.
      Surface Plasmon Resonance imaging (SPRi) was used as a sensitive and real-time
      imaging based detector for various gaseous chemical mixtures and good gas
      chromatographs were obtained. The system integrated a home-made miniaturized
      molecular sieve packed spiral micro-channel column with the SPRi imaging chip and
      real-time chemical separation and detection were demonstrated using alkanes. The
      chemical separation processes were simulated using COMSOL and matched well with
      experimental results. The system enabled the study of chemical separation
      processes in real-time by miniaturizing and integrating the Micro-GC separation
      and detection units. This approach can be expanded to multidimensional GC
      development.

PMID- 30220883
TI  - Treatment of Chagas Disease in the United States.
AB  - Purpose of Review: Chagas disease (CD) is endemic to much of Latin America, but
      also present in the United States (U.S.). Following a lengthy asymptomatic
      period, CD produces serious cardiac or gastrointestinal complications in 30-40%
      of people. Less than 1% of the estimated six million cases in the Americas,
      including 326,000-347,000 in the U.S., are diagnosed. Infected persons are
      typically unaware and the bulk of clinicians are unfamiliar with current
      treatment guidelines. This review provides U.S. and other clinicians with the
      latest knowledge of CD treatment. Recent Findings: Chagas cardiomyopathy (CCM)
      causes severe fibrosis and autonomic damage in the myocardium. Eliminating the
      parasite through antitrypanosomal therapy with benznidazole, a nitroimidazole
      derivative or nifurtimox, a nitrofuran compound, potentially prevents heart
      failure and other sequelae of advanced CCM. Benznidazole, recently approved by
      the U.S. Food and Drug Administration (FDA) for children 2-12 years old, is the
      first-line therapy; optimal dosages are currently being studied. Antitrypanosomal
      therapy prevents congenital transmission; produces high cure rates for acute,
      congenital, and early chronic cases; and improves clinical outcomes in adult
      chronic indeterminate cases. However, this benefit was not observed in a large
      clinical trial that included patients with advanced CCM. Summary: Treatment with
      antitrypanosomal drugs can cure CD in acute, congenital, and early chronic cases
      and provides improved clinical outcomes for chronic indeterminate cases. This
      treatment should be offered as early as possible, before advanced CCM develops.

PMID- 30220887
TI  - OPTIMIZATION OF SCALE-UP SYNTHESIS OF ANTI-CANCER CERAMIDE ANALOG 315.
AB  - Ceramides, serve as central mediators in sphingolipid metabolism and signaling
      pathways. They function in signaling events which induce apoptosis, cell cycle
      arrest, and autophagic responses. In cancer cells, ceramide levels are often
      suppressed by the up-regulation of ceramide-metabolizing enzymes or the down
      regulation of ceramide-generating enzymes, resulting in increased cancer cell
      survival. Chemotherapeutic drugs and radiation therapy have been shown to
      increase intracellular ceramide levels leading to anti-cancer effects. Anti
      cancer effects have also been seen in cancer cells with the use of exogenous
      short-chain ceramides. Our laboratory has synthesized a library of ceramide
      analogs and tested their effects on breast cancer cell lines. Analog 315 has been
      shown to be the most effective ceramide analog in our library. Here, we are
      reporting a large-scale synthesis of that analog is reported.

PMID- 30220888
TI  - Moral Hazard in Health Insurance: What We Know and How We Know It.
AB  - We describe research on the impact of health insurance on healthcare spending
      ("moral hazard"), and use this context to illustrate the value of and important
      complementarities between different empirical approaches. One common approach is
      to emphasize a credible research design; we review results from two randomized
      experiments, as well as some quasi-experimental studies. This work has produced
      compelling evidence that moral hazard in health insurance exists-that is,
      individuals, on average, consume less healthcare when they are required to pay
      more for it out of pocket-as well as qualitative evidence about its nature. These
      studies alone, however, provide little guidance for forecasting healthcare
      spending under contracts not directly observed in the data. Therefore, a second
      and complementary approach is to develop an economic model that can be used out
      of sample. We note that modeling choices can be consequential: different economic
      models may fit the reduced form but deliver different counterfactual predictions.
      An additional role of the more descriptive analyses is therefore to provide
      guidance regarding model choice.

PMID- 30220889
TI  - httk: R Package for High-Throughput Toxicokinetics.
AB  - Thousands of chemicals have been profiled by high-throughput screening programs
      such as ToxCast and Tox21; these chemicals are tested in part because most of
      them have limited or no data on hazard, exposure, or toxicokinetics.
      Toxicokinetic models aid in predicting tissue concentrations resulting from
      chemical exposure, and a "reverse dosimetry" approach can be used to predict
      exposure doses sufficient to cause tissue concentrations that have been
      identified as bioactive by high-throughput screening. We have created four
      toxicokinetic models within the R software package httk. These models are
      designed to be parameterized using high-throughput in vitro data (plasma protein
      binding and hepatic clearance), as well as structure-derived physicochemical
      properties and species-specific physiological data. The package contains tools
      for Monte Carlo sampling and reverse dosimetry along with functions for the
      analysis of concentration vs. time simulations. The package can currently use
      human in vitro data to make predictions for 553 chemicals in humans, rats, mice,
      dogs, and rabbits, including 94 pharmaceuticals and 415 ToxCast chemicals. For 67
      of these chemicals, the package includes rat-specific in vitro data. This package
      is structured to be augmented with additional chemical data as they become
      available. Package httk enables the inclusion of toxicokinetics in the
      statistical analysis of chemicals undergoing high-throughput screening.

PMID- 30220891
TI  - Subtidal Benthic Invertebrates Shifting Northward Along the US Atlantic Coast.
AB  - Numerous marine and terrestrial species have shifted their ranges poleward in
      response to warming from global climate change. However, few studies have
      examined range shifts of subtidal benthic communities in estuarine and nearshore
      waters. This study examined 20 years (1990-2010) of occurrence and abundance data
      of soft-bottom, benthic invertebrates along the Atlantic coast of the USA. Data
      from two biogeographic provinces (Carolinian and Virginian), which spanned 15
      degrees  of latitude from mid-Florida to Cape Cod, were extracted from a national
      coastal assessment program. Mean water temperatures increased significantly
      during the study period, bottom water by 1.6  degrees C and surface water by 1.7 
      degrees C. Of 25 species with significant changes in centers of abundance (out of
      the 30 most prevalent), 18 (60%) shifted northward and 7 (23%) shifted southward.
      Species that shifted north moved an average distance of 181 km, in contrast with
      65 km for species that shifted south. The southern limits of 22 species showed
      significant northward shifts; because there was little change in northern limits,
      this resulted in an average 25% range contraction. Community composition changed
      during the study period, most notably in southern latitudes. Five Carolinian
      species surmounted their northerly biogeographic boundary. Consequences of these
      range shifts include changes in benthic community structure and function, which
      have strong implications for ecosystem functioning and services including changes
      in fisheries dependent upon benthic prey.

PMID- 30220890
TI  - Phosphotyrosine profiling of human cerebrospinal fluid.
AB  - Background: Cerebrospinal fluid (CSF) is an important source of potential
      biomarkers that affect the brain. Biomarkers for neurodegenerative disorders are
      needed to assist in diagnosis, monitoring disease progression and evaluating
      efficacy of therapies. Recent studies have demonstrated the involvement of
      tyrosine kinases in neuronal cell death. Thus, neurodegeneration in the brain is
      related to altered tyrosine phosphorylation of proteins in the brain and
      identification of abnormally phosphorylated tyrosine peptides in CSF has the
      potential to ascertain candidate biomarkers for neurodegenerative disorders.
      Methods: In this study, we used an antibody-based tyrosine phosphopeptide
      enrichment method coupled with high resolution Orbitrap Fusion Tribrid Lumos
      Fourier transform mass spectrometer to catalog tyrosine phosphorylated peptides
      from cerebrospinal fluid. The subset of identified tyrosine phosphorylated
      peptides was also validated using parallel reaction monitoring (PRM)-based
      targeted approach. Results: To date, there are no published studies on global
      profiling of phosphotyrosine modifications of CSF proteins. We carried out
      phosphotyrosine profiling of CSF using an anti-phosphotyrosine antibody-based
      enrichment and analysis using high resolution Orbitrap Fusion Lumos mass
      spectrometer. We identified 111 phosphotyrosine peptides mapping to 66 proteins,
      which included 24 proteins which have not been identified in CSF previously. We
      then validated a set of 5 tyrosine phosphorylated peptides in an independent set
      of CSF samples from cognitively normal subjects, using a PRM-based targeted
      approach. Conclusions: The findings from this deep phosphotyrosine profiling of
      CSF samples have the potential to identify novel disease-related phosphotyrosine
      containing peptides in CSF.

PMID- 30220892
TI  - Multicultural Transitions: Caregiver Presence and Language-Concordance at
      Discharge.
AB  - Introduction: Patients with low health literacy (HL) and minority patients
      encounter many challenges during hospital to community transitions. We assessed
      care transitions of minority patients with various HL levels and tested whether
      presence of caregivers and provision of language-concordant care are associated
      with better care transitions. Methods: A prospective cohort study of 598 internal
      medicine patients, Hebrew, Russian, or Arabic native speakers, at a tertiary
      medical center in central Israel, from 2013 to 2014.HL was assessed at baseline
      with the Brief Health Literacy Screen. A follow-up telephone survey was used to
      administer the Care Transition Measure [CTM] and to assess, caregiver presence
      and patient-provider language-concordance at discharge. Results: Patients with
      low HL and without language-concordance or caregiver presence had the lowest CTM
      scores (33.1, range 0-100). When language-concordance and caregivers were
      available, CTM scores did not differ between the medium-high and low HL groups
      (68.7 and 66.9, respectively, p = 0.118). The adjusted analysis, showed that
      language-concordance and caregiver presence during discharge moderate the
      relationship between HL and patients' care transition experience (p < 0.001).
      Conclusions: Language-concordance care and caregiver presence are associated with
      higher patients' ratings of the transitional-care experience among patients with
      low HL levels and among minorities.

PMID- 30220893
TI  - The Core Dimensions of Integrated Care: A Literature Review to Support the
      Development of a Comprehensive Framework for Implementing Integrated Care.
AB  - Objective: As part of the EU-funded Project INTEGRATE, the research sought to
      develop an evidence-based understanding of the key dimensions and items of
      integrated care associated with successful implementation across varying country
      contexts and relevant to different chronic and/or long-term conditions. This
      paper identifies the core dimensions of integrated care based on a review of
      previous literature on the topic. Methodology: The research reviewed literature
      evidence from the peer-reviewed and grey literature. It focused on reviewing
      research articles that had specifically developed frameworks on integrated care
      and/or set out key elements for successful implementation. The search initially
      focused on three main scientific journals and was limited to the period from 2006
      to 2016. Then, the research snowballed the references from the selected published
      studies and engaged leading experts in the field to supplement the identification
      of relevant literature. Two investigators independently reviewed the selected
      articles using a standard data collection tool to gather the key elements
      analyzed in each article. Results: A total of 710 articles were screened by title
      and abstract. Finally, 18 scientific contributions were selected, including
      studies from grey literature and experts' suggestions. The analysis identified
      175 items grouped in 12 categories. Conclusions: Most of the key factors reported
      in the literature derive from studies that developed their frameworks in specific
      contexts and/or for specific types of conditions. The identification and
      classification of the elements from this literature review provide a basis to
      develop a comprehensive framework enabling standardized descriptions and
      benchmarking of integrated care initiatives carried out in different contexts.

PMID- 30220894
TI  - Finding the Integrated Care Evidence Base in PubMed and Beyond: A Bibliometric
      Study of the Challenges.
AB  - Introduction: Integrated care research evidence should be optimally visible and
      accessible to stakeholders. This study examines the contribution of specific
      databases to the discovery of integrated care evidence, and tests the usefulness
      of Medical Subject Heading (MeSH) indexing of this literature within PubMed.
      Methods: We used bibliometric methods to analyse the integrated care literature
      indexed within six databases between 2007 and 2016. An international expert
      advisory group assessed the relevance of citations randomly retrieved from PubMed
      using MeSH term 'Delivery of Health Care, Integrated'. Results: Integrated care
      evidence is diffuse, spread across many journals. Between 2007 and 2016,
      integrated care citations grew substantially, with the rate of increase highest
      in Embase. PubMed contributes the largest proportion of unique citations
      (citations not included in any of the other databases analysed), followed by
      Embase, PsycINFO and CINAHL. On average, expert reviewers rated 42.5% of
      citations retrieved by MeSH term 'Delivery of Health Care, Integrated' as
      relevant to integrated care. When these citations were dual reviewed, inter-rater
      agreement was low. Conclusion: MeSH terms alone are insufficient to retrieve
      integrated care content from PubMed. Embase and CINAHL contain unique content not
      found in PubMed that should not be overlooked. A validated search filter is
      proposed to simplify the process of finding integrated care research for
      clinicians, managers and decision-makers.

PMID- 30220895
TI  - Care Coordination as Imagined, Care Coordination as Done: Findings from a Cross
      national Mental Health Systems Study.
AB  - Introduction: Care coordination is intended to ensure needs are met and
      integrated services are provided. Formalised processes for the coordination of
      mental health care arrived in the UK with the introduction of the care programme
      approach in the early 1990s. Since then the care coordinator role has become a
      central one within mental health systems. Theory and methods: This paper
      contrasts care coordination as work that is imagined with care coordination as
      work that is done. This is achieved via a critical review of policy followed by a
      qualitative analysis of interviews, focusing on day-to-day work, conducted with
      28 care coordinators employed in four NHS organisations in England and two in
      Wales. Findings: Care coordination is imagined as a vehicle for the provision of
      collaborative, recovery-focused, care. Those who practise care coordination are
      concerned with the quality of their relationships with service users and the
      tailoring of services, but limits exist to collaboration and open discussion.
      Care coordinators describe doing necessary work connecting people and the system
      of care. However, this work also brings significant administrative demands, is
      subject to performance management which distorts its primary purpose, and in a
      context of scarce resources promotes generic professional roles. Conclusion: Care
      coordination must be done. However, it is not consistently being done in the way
      policymakers imagine, and in the real world of work can be done differently.

PMID- 30220896
TI  - A Scoping Review of Facilitators of Multi-Professional Collaboration in Primary
      Care.
AB  - Introduction: Multi-professional collaboration (MPC) is essential for the
      delivery of effective and comprehensive care services. As in other European
      countries, primary care in Norway is challenged by altered patient values and the
      increased expectations of health administrations to participate in team-based
      care. This scoping review reports on the organisational, processual, relational
      and contextual facilitators of collaboration between general practitioners (GP)
      and other healthcare professionals (HCPs) in primary care. Methods: A systematic
      search in specialist and Scandinavian databases retrieved 707 citations.
      Following the inclusion criteria, nineteen studies were considered eligible and
      examined according to Arksey and O'Malley's methodological framework for scoping
      reviews. The retrieved literature was analysed employing a content analysis
      approach. A group of stakeholders commented on study findings to enhance study
      validity. Results: Primary care research into MPC is immature and emerging in
      Norway. Our analysis showed that introducing common procedures for documentation
      and handling of patient data, knowledge sharing, and establishing local
      specialised multi-professional teams, facilitates MPC. The results indicate that
      advancements in work practices benefit from an initial system-level foundation
      with focus on local management and MPC leadership. Further, our results show that
      it is preferable to enhance collaborative skills before introducing new
      professional teams, roles and responsibilities. Investing in professional
      relations could build trust, respect and continuity. In this respect, sufficient
      time must be allocated during the working day for professionals to share
      reflections and engage in mutual learning. Conclusion: There is a paucity of
      research concerning the application and management of MPC in Norwegian primary
      care. The work practices and relations between professionals, primary care
      institutions and stakeholders on a macro level is inadequate. Health care is a
      complex system in which HCPs need managerial support to harvest the untapped
      benefits of MPC in primary care. As international research demonstrates, local
      managers must be supported with infrastructure on a macro level to understand the
      embedding of practice and look at what professionals actually do and how they
      work.

PMID- 30220898
TI  - Night Light Pollution and Ocular Fatigue.

PMID- 30220897
TI  - Implementation of a Stepwise, Multidisciplinary Intervention for Pain and
      Challenging Behaviour in Dementia (STA OP!): A Process Evaluation.
AB  - Background: A stepwise, multidisciplinary and multicomponent intervention (called
      STA OP!) was implemented in Dutch nursing home units, which included a
      comprehensive multidisciplinary team training. A cluster-randomised controlled
      trial showed that the intervention reduced symptoms of pain and challenging
      behaviour. Objectives: To describe the experiences around the implementation of
      the intervention; to examine the extent to which the STA OP! intervention was
      delivered and implemented as intended (at the level of the team, and the
      individual resident/professional); and to understand factors influencing the
      implementation process. Methods: A process evaluation was performed using a mixed
      methods design encompassing several data sources. Quantitative data (i.e. from
      the written evaluations by healthcare professionals, management, and the research
      database) were analysed using descriptive statistics. Qualitative data (i.e. semi
      structured interviews, notes, completed intervention forms, and written
      evaluations) were analysed according to the principles of thematic analysis. The
      implementation process and the influencing factors were categorised according to
      the i) organisational level, ii) the team level, and iii) the level of the
      individual resident/professional. Results: In total, 39.2% of the residents with
      pain and/or challenging behaviour were treated following the stepwise approach of
      the STA OP! intervention. The training manual and forms used were found to be
      relevant and feasible. Factors inhibiting the implementation process at the i)
      organisational level concerned instability of the organisation and the team (e.g.
      involvement in multiple projects/new innovations, staff turnover/absence of
      essential disciplines, and/or high workload). At the team level (ii), we found
      that presence of a person with a motivational leadership style facilitated the
      implementation. Also, interdisciplinary cooperation through the design/setting of
      the multidisciplinary training, securing the intervention by use of clear
      agreements, and written reporting or transfers facilitated implementation. At the
      individual level (iii), perceived value of the stepwise working method, and
      enhanced awareness facilitated the implementation. Conclusion: Although the
      intervention was not implemented as planned, the intervention empowered
      healthcare professionals and increased their awareness of the signals of pain and
      challenging behaviour. Future implementation of the intervention should start on
      units with a motivational leader, and specific features of the organisation and
      the team should be considered to facilitate implementation, e.g. stability,
      support, and shared focus to change.

PMID- 30220899
TI  - Seeing is believing: the Bicoid protein reveals its path.
AB  - In this commentary, I will review the latest findings on the Bicoid (Bcd)
      morphogen in Drosophila, a paradigm for gradient formation taught to biology
      students for more than two decades. "Seeing is believing" also summarizes the
      erroneous steps that were needed to elucidate the mechanisms of gradient
      formation and the path of movement of Bcd. Initially proclaimed as a dogma in
      1988 and later incorporated into the SDD model where the broad diffusion of Bcd
      throughout the embryo was the predominant step leading to gradient formation, the
      SDD model was irrefutable for more than two decades until first doubts were
      raised in 2007 regarding the diffusion properties of Bcd associated with the SDD
      model. This led to re-thinking of the issue and the definition of a new model,
      termed the ARTS model which could explain most of the physical constraints that
      were inherently associated with the SDD model. In the ARTS model, gradient
      formation is mediated by the mRNA which is redistributed along cortical
      microtubules to form a mRNA gradient which is translated to form the protein
      gradient. Contrary to the SDD model, there is no Bcd diffusion from the tip. The
      ARTS model is also compatible with the observed cortical movement of Bcd. I will
      critically compare the SDD and the ARTS models as well as other models, analyze
      the major differences, and highlight the path where Bcd is localized during early
      nuclear cycles.

PMID- 30220900
TI  - Respiratory Rate Estimation by Using ECG, Impedance, and Motion Sensing in Smart
      Clothing.
AB  - The needs for light-weight and soft smart clothing in homecare have been rising
      since the past decade. Many smart textile sensors have been developed and applied
      to automatic physiological and user-centered environmental status recognition. In
      the present study, we propose wearable multi-sensor smart clothing for homecare
      monitoring based on an economic fabric electrode with high elasticity and low
      resistance. The wearable smart clothing integrated with heterogeneous sensors is
      capable to measure multiple human biosignals (ECG and respiration), acceleration,
      and gyro information. Five independent respiratory signals (electric impedance
      plethysmography, respiratory induced frequency variation, respiratory induced
      amplitude variation, respiratory induced intensity variation, and respiratory
      induced movement variation) are obtained. The smart clothing can provide accurate
      respiratory rate estimation by using three different techniques (Naive Bayes
      inference, static Kalman filter, and dynamic Kalman filter). During the static
      sitting experiments, respiratory induced frequency variation has the best
      performance; whereas during the running experiments, respiratory induced
      amplitude variation has the best performance. The Naive Bayes inference and
      dynamic Kalman filter have shown good results. The novel smart clothing is soft,
      elastic, and washable and it is suitable for long-term monitoring in homecare
      medical service and healthcare industry.

PMID- 30220901
TI  - Strength Analyses of Screws for Femoral Neck Fractures.
AB  - This article represents a multidisciplinary approach to biomechanics (engineering
      + medicine) in the field of "collum femoris" fractures. One possible treatment
      method for femoral neck fractures, especially for young people, is the
      application of cancellous (i.e. lag or femoral) screws (with full or cannulated
      cross-section) made of Ti6Al4V or stainless steel. This paper therefore aims to
      offer our own numerical model of cancellous screws together with an assessment of
      them. The new, simple numerical model presented here is derived together with
      inputs and boundary conditions and is characterized by rapid solution. The model
      is based on the theory of beams on an elastic foundation and on 2nd order theory
      (set of three differential 4th order equations, combination of pressure and
      bending stress-deformation states). It presents the process for calculating
      displacements, slopes, bending moments, stresses etc. Two examples (i.e.
      combinations of cancellous screws with full or cannulated cross-section made of
      stainless steel or Ti6Al4V material) are presented and evaluated (i.e. their
      displacement, slopes, bending moments, normal forces, shearing forces and
      stresses). Future developments and other applications are also proposed and
      mentioned.

PMID- 30220902
TI  - Web-Based Experience Sharing Platform on Medical Device Incidents for Clinical
      Engineers in Hospitals.
AB  - The aim of this study was to establish a web-based platform for exchanging
      medical device management and maintenance experiences to enhance the professional
      competency of clinical engineers (CEs), which ensures the quality of medical
      devices and increases patients' satisfaction with medical services. Medical
      devices play an essential role in diagnosis and disease management. CEs are
      responsible for providing functional medical devices that contribute worthwhile
      functions to a medical service to improve patients' health and safety. The
      purpose of the platform is to facilitate collection and sharing of medical device
      incidents experiences to improve CEs' capability. To provide useful and practical
      information for CEs, an event review committee, composed of experts with more
      than 20 years of clinical engineering experience who were recruited as reviewers,
      was established under the platform. Cases submitted to the platform were required
      to have comprehensive descriptions of the device and events. Each case was
      evaluated by at least two reviewers based on five evaluation indices: (1)
      severity, (2) breadth, (3) frequency, (4) insidiousness, and (5) correctness.
      After being reviewed, each final report was published on the platform to be
      shared with the event submitters and other members. The results show that 116
      staffs from 32 different hospitals, registered to join this platform. From
      January 2015 to December 2016, 70 events were submitted with 56 reports. This
      study also assessed the platform's benefits for CEs. A total of 93 respondents
      completed a questionnaire survey: 93% of the CEs agreed that the information from
      the platform helped them do their job. The web-based platform has high value as
      an experience-sharing interface for medical devices. The CEs obtained extremely
      useful information from the platform for medical device management and their
      daily duties. This study provided an online training model with systematic
      methods to improve the quality and effectiveness of medical device management.

PMID- 30220903
TI  - A Comparison of Major Petroleum Life Cycle Models.
AB  - Many organizations have attempted to develop an accurate well-to-pump life cycle
      model of petroleum products in order to inform decision makers of the
      consequences of its use. Our paper studies five of these models, demonstrating
      the differences in their predictions and attempting to evaluate their data
      quality. Carbon dioxide well-to-pump emissions for gasoline showed a variation of
      35%, and other pollutants such as ammonia and particulate matter varied up to
      100%. Differences in allocation do not appear to explain differences in
      predictions. Effects of these deviations on well-to-wheels passenger vehicle and
      truck transportation life cycle models may be minimal for effects such as global
      warming potential (6% spread), but for respiratory effects of criteria pollutants
      (41% spread) and other impact categories, they can be significant. A data quality
      assessment of the models' documentation revealed real differences between models
      in temporal and geographic representativeness, completeness, as well as
      transparency. Stakeholders may need to consider carefully the tradeoffs inherent
      when selecting a model to conduct life cycle assessments for systems that make
      heavy use of petroleum products.

PMID- 30220904
TI  - On the automated translational execution of the action language for foundational
      UML.
AB  - To manage the rapidly growing complexity of software development, abstraction and
      automation have been recognised as powerful means. Among the techniques pushing
      for them, model-driven engineering has gained increasing attention from industry
      for, among others, the possibility to automatically generate code from models. To
      generate fully executable code, models should describe complex behaviours. While
      pragmatically this is achieved by employing programming languages for defining
      actions within models, the abstraction gap between modelling and programming
      languages can undermine consistency between models and code as well as
      analysability and reusability of models. In light of this, model-aware action
      languages should be preferred. This is the case of the Action Language for
      Foundational UML (ALF). In this paper, we provide a solution for the fully
      automated translational execution of ALF towards C++. Additionally, we give an
      insight on how to simplify the transition from the use of programming languages
      for modelling fine-grained behaviours to model-aware action languages in
      industrial MDE. The solution presented in this paper has been assessed on
      industrial applications to verify its applicability to complex systems as well as
      its scalability.

PMID- 30220905
TI  - The Train Benchmark: cross-technology performance evaluation of continuous model
      queries.
AB  - In model-driven development of safety-critical systems (like automotive, avionics
      or railways), well-formedness of models is repeatedly validated in order to
      detect design flaws as early as possible. In many industrial tools, validation
      rules are still often implemented by a large amount of imperative model traversal
      code which makes those rule implementations complicated and hard to maintain.
      Additionally, as models are rapidly increasing in size and complexity, efficient
      execution of validation rules is challenging for the currently available tools.
      Checking well-formedness constraints can be captured by declarative queries over
      graph models, while model update operations can be specified as model
      transformations. This paper presents a benchmark for systematically assessing the
      scalability of validating and revalidating well-formedness constraints over large
      graph models. The benchmark defines well-formedness validation scenarios in the
      railway domain: a metamodel, an instance model generator and a set of well
      formedness constraints captured by queries, fault injection and repair operations
      (imitating the work of systems engineers by model transformations). The benchmark
      focuses on the performance of query evaluation, i.e. its execution time and
      memory consumption, with a particular emphasis on reevaluation. We demonstrate
      that the benchmark can be adopted to various technologies and query engines,
      including modeling tools; relational, graph and semantic databases. The Train
      Benchmark is available as an open-source project with continuous builds from
      https://github.com/FTSRG/trainbenchmark.

PMID- 30220906
TI  - Corrigendum: Brief Mindfulness Meditation Improves Attention in Novices: Evidence
      From ERPs and Moderation by Neuroticism.
AB  - [This corrects the article DOI: 10.3389/fnhum.2018.00315.].

PMID- 30220907
TI  - Non-Image Forming Effects of Light on Brainwaves, Autonomic Nervous Activity,
      Fatigue, and Performance.
AB  - Fatigue and sleepiness are one of the main causes of human errors and accidents
      in the workplace. The empirical evidence has approved that, in addition to
      stimulating the visual system, light elicits brain responses, which affect
      physiological and neurobehavioral human functions, known as the non-image forming
      (NIF) effects of light. As recent evidences have shown the positive effects of
      red or low correlated color temperature white light on alertness and performance,
      we investigated whether exposure to 2564 K light could improve subjective and
      objective measures of alertness and performance compared with 7343 K, 3730 K, and
      dim light (DL) conditions during the daytime. Twenty two healthy participants
      were exposed to the light while they were performing a sustained attention task
      and their electroencephalogram (EEG) and electrocardiogram (ECG) were recorded.
      Both 2564 K and 7343 K conditions significantly reduced EEG alpha-power compared
      with the DL and 3730 K conditions. Moreover, the 2564 K, 7343 K, and 3730 K
      conditions significantly reduced subjective fatigue, sleepiness and increased
      heart rate and performance compared with the DL condition. Furthermore, the
      effects of light conditions on alertness and performance varied over the day so
      that more effective responses were observed during the afternoon hours. These
      findings suggest that light interventions can be applied to improve daytime
      performance.

PMID- 30220909
TI  - I love you from the bottom of my hypothalamus: The role of stress physiology in
      romantic pair bond formation and maintenance.
AB  - Monogamous pair bonds helped solve ancestral problems pertinent to our survival
      as a species. In order for these pair bonds to succeed, biological systems were
      co-opted to support and reinforce attachment bonds through feelings of pleasure
      and reward. One of the major biological systems that may play an important role
      in the formation of romantic attachments is the stress response system (autonomic
      nervous system and hypothalamic-pituitary-adrenal axis). Research suggests
      attraction, mate preference, and emotional connectedness may be supported by the
      activation or inhibition of the stress response system. Further, as romantic
      relationships progress, new findings suggest partners' physiological patterns
      coalesce, potentially serving a regulatory function that reinforces the pair bond
      and affects overall well-being. Based on this evidence, the current paper puts
      forth the Physiology of Romantic Pair Bond Initiation and Maintenance Model,
      which will provide researchers with a new perspective on the function of the
      stress response system in romantic relationships.

PMID- 30220908
TI  - Temporal synchrony and audiovisual integration of speech and object stimuli in
      autism.
AB  - Background: Individuals with Autism Spectrum Disorders (ASD) have been shown to
      have multisensory integration deficits, which may lead to problems perceiving
      complex, multisensory environments. For example, understanding audiovisual speech
      requires integration of visual information from the lips and face with auditory
      information from the voice, and audiovisual speech integration deficits can lead
      to impaired understanding and comprehension. While there is strong evidence for
      an audiovisual speech integration impairment in ASD, it is unclear whether this
      impairment is due to low level perceptual processes that affect all types of
      audiovisual integration or if it is specific to speech processing. Method: Here,
      we measure audiovisual integration of basic speech (i.e., consonant-vowel
      utterances) and object stimuli (i.e., a bouncing ball) in adolescents with ASD
      and well-matched controls. We calculate a temporal window of integration (TWI)
      using each individual's ability to identify which of two videos (one temporally
      aligned and one misaligned) matches auditory stimuli. The TWI measures tolerance
      for temporal asynchrony between the auditory and visual streams, and is an
      important feature of audiovisual perception. Results: While controls showed
      similar tolerance of asynchrony for the simple speech and object stimuli,
      individuals with ASD did not. Specifically, individuals with ASD showed less
      tolerance of asynchrony for speech stimuli compared to object stimuli. In
      individuals with ASD, decreased tolerance for asynchrony in speech stimuli was
      associated with higher ratings of autism symptom severity. Conclusions: These
      results suggest that audiovisual perception in ASD may vary for speech and object
      stimuli beyond what can be accounted for by stimulus complexity.

PMID- 30220911
TI  - Label-free electrochemical sensor to investigate the effect of tocopherol on
      generation of superoxide ions following UV irradiation.
AB  - Background: Generation of reactive oxygen species (ROS), triggered by ultraviolet
      radiation (UVR), is associated with carcinogenesis of the skin. UV irradiation
      induced superoxide anion (O2*-) is the key ROS involved in the cellular damage.
      The cytoprotective efficacy of an unknown anti-oxidant compound can be evaluated
      by analyzing the production of O2*- from treated cells. Methods: In this study, a
      glass carbon electrode functionalized with nanotube@DNA-Mn3(PO4)2 composite was
      applied to quantitative determination of generation of highly unstable O2*- from
      the melanoma A375 cell line following UVR(UV, UVA and UVB). In addition, the
      cytoprotective efficacy of anti-oxidant alpha-tocopherol was evaluated by
      quantifying the production of O2*-. Results: The results showed that, UVR
      triggers generation of O2*- in melanoma A375 cells, and alpha-tocopherol is
      effective in diminishing the production of O2*- following UV irradiation. By
      comparing the conventional cell-survival assays results, we found that our simple
      and quick electrochemical sensing method can quantify O2*- generation through the
      biological activity of an anti-oxidant compound (alpha-tocopherol). Conclusion:
      Our label-free electrochemical quantification method for ROS (O2*- major) in
      cells facing UVR stress demonstrates its potential application for high
      throughput screening of anti-oxidation compounds.

PMID- 30220910
TI  - Applications of genotyping by sequencing in aquaculture breeding and genetics.
AB  - Selective breeding is increasingly recognized as a key component of sustainable
      production of aquaculture species. The uptake of genomic technology in
      aquaculture breeding has traditionally lagged behind terrestrial farmed animals.
      However, the rapid development and application of sequencing technologies has
      allowed aquaculture to narrow the gap, leading to substantial genomic resources
      for all major aquaculture species. While high-density single-nucleotide
      polymorphism (SNP) arrays for some species have been developed recently, direct
      genotyping by sequencing (GBS) techniques have underpinned many of the advances
      in aquaculture genetics and breeding to date. In particular, restriction-site
      associated DNA sequencing (RAD-Seq) and subsequent variations have been
      extensively applied to generate population-level SNP genotype data. These GBS
      techniques are not dependent on prior genomic information such as a reference
      genome assembly for the species of interest. As such, they have been widely
      utilized by researchers and companies focussing on nonmodel aquaculture species
      with relatively small research communities. Applications of RAD-Seq techniques
      have included generation of genetic linkage maps, performing genome-wide
      association studies, improvements of reference genome assemblies and, more
      recently, genomic selection for traits of interest to aquaculture like growth,
      sex determination or disease resistance. In this review, we briefly discuss the
      history of GBS, the nuances of the various GBS techniques, bioinformatics
      approaches and application of these techniques to various aquaculture species.

PMID- 30220912
TI  - Machine learning analysis of microbial flow cytometry data from nanoparticles,
      antibiotics and carbon sources perturbed anaerobic microbiomes.
AB  - Background: Flow cytometry, with its high throughput nature, combined with the
      ability to measure an increasing number of cell parameters at once can surpass
      the throughput of prevalent genomic and metagenomic approaches in the study of
      microbiomes. Novel computational approaches to analyze flow cytometry data will
      result in greater insights and actionability as compared to traditional tools
      used in the analysis of microbiomes. This paper is a demonstration of the
      fruitfulness of machine learning in analyzing microbial flow cytometry data
      generated in anaerobic microbiome perturbation experiments. Results: Autoencoders
      were found to be powerful in detecting anomalies in flow cytometry data from
      nanoparticles and carbon sources perturbed anaerobic microbiomes but was marginal
      in predicting perturbations due to antibiotics. A comparison between different
      algorithms based on predictive capabilities suggested that gradient boosting (GB)
      and deep learning, i.e. feed forward artificial neural network with three hidden
      layers (DL) were marginally better under tested conditions at predicting overall
      community structure while distributed random forests (DRF) worked better for
      predicting the most important putative microbial group(s) in the anaerobic
      digesters viz. methanogens, and it can be optimized with better parameter tuning.
      Predictive classification patterns with DL (feed forward artificial neural
      network with three hidden layers) were found to be comparable to previously
      demonstrated multivariate analysis. The potential applications of this approach
      have been demonstrated for monitoring the syntrophic resilience of the anaerobic
      microbiomes perturbed by synthetic nanoparticles as well as antibiotics.
      Conclusion: Machine learning can benefit the microbial flow cytometry research
      community by providing rapid screening and characterization tools to discover
      patterns in the dynamic response of microbiomes to several stimuli.

PMID- 30220914
TI  - Special theme article: science and sociology of footwear.

PMID- 30220915
TI  - Tensile properties and critical current strain limits of reinforced Bi-2212
      conductors for high field magnets.
AB  - We study here the effect of axial strain on the degradation of the critical
      current Ic for bare and reinforced, overpressure processed Bi-2212 conductors. We
      show that reinforcement markedly improves the conductor's stress limit, doubling
      it from ~150 MPa in the bare conductor to ~300 MPa when reinforced. We find also
      that certain processes used to reinforce the conductor slightly reduce the Ic
      degradation strain limit from ~0.6% to ~0.4%. Stress vs strain data taken from
      the samples studied here has been used to create a finite element model to
      explore the feasibility of using a reinforced Bi-2212 strand (produced by Solid
      Material Solutions) in a small test coil. The model predicts an IC limited coil
      with a maximum hoop strain of 0.31%, well below the experimentally verified
      strain limit, and is designed to lead to Bi-2212 coils that are not strain
      limited, but Ic limited.

PMID- 30220916
TI  - Governing in the Anthropocene: are there cyber-systemic antidotes to the malaise
      of modern governance?
AB  - Abstract: The Anthropocene imposes new challenges for governments, demanding
      capabilities for dealing with complexity and uncertainty. In this paper we
      examine how effective governing of social-biophysical dynamics is constrained by
      current processes and systems of government. Framing choices and structural
      determinants combine to create governance deficits in multiple domains,
      particularly in relation to the governing of complex larger-scale social
      biophysical systems. Attempts to build capability for governing 'wicked problems'
      are relevant to sustainability science and Anthropocene governance, but these
      have mostly failed to become institutionalised. Two cases studies are reported to
      elucidate how the systemic dynamics of governing operate and fail in relation to
      espoused purpose. In the UK attempts to enact 'joined-up' government' during the
      years of New Labour government reveal systemic flaws and consistent praxis
      failures. From Australia we report on water governance reforms with implications
      for a wide range of complex policy issues. We conclude that innovations are
      needed to build capacity for governing the unfolding surprises and inherent
      uncertainties of the Anthropocene. These include institutionalising, or
      structural incorporation, of cyber-systemic thinking/practices that can also
      enhance empowerment and creativity that underpins sustainability science.
      Graphical abstract: 

PMID- 30220917
TI  - Reconnecting with nature for sustainability.
AB  - Calls for humanity to 'reconnect to nature' have grown increasingly louder from
      both scholars and civil society. Yet, there is relatively little coherence about
      what reconnecting to nature means, why it should happen and how it can be
      achieved. We present a conceptual framework to organise existing literature and
      direct future research on human-nature connections. Five types of connections to
      nature are identified: material, experiential, cognitive, emotional, and
      philosophical. These various types have been presented as causes, consequences,
      or treatments of social and environmental problems. From this conceptual base, we
      discuss how reconnecting people with nature can function as a treatment for the
      global environmental crisis. Adopting a social-ecological systems perspective, we
      draw upon the emerging concept of 'leverage points'-places in complex systems to
      intervene to generate change-and explore examples of how actions to reconnect
      people with nature can help transform society towards sustainability.

PMID- 30220919
TI  - From disagreements to dialogue: unpacking the Golden Rice debate.
AB  - Transgenic Golden Rice has been hailed as a practical solution to vitamin A
      deficiency, but has also been heavily criticized. To facilitate a balanced view
      on this polarized debate, we investigated existing arguments for and against
      Golden Rice from a sustainability science perspective. In a structured literature
      review of peer-reviewed publications on Golden Rice, we assessed to what extent
      64 articles addressed 70 questions covering different aspects of sustainability.
      Using cluster analysis, we grouped the literature into two major branches,
      containing two clusters each. These clusters differed in the range and nature of
      the sustainability aspects addressed, disciplinary affiliation and overall
      evaluation of Golden Rice. The 'biotechnological' branch (clusters: 'technical
      effectiveness' and 'advocacy') was dominated by the natural sciences, focused on
      biophysical plant-consumer interactions, and evaluated Golden Rice positively. In
      contrast, the 'socio-systemic' branch (clusters: 'economic efficiency' and
      'equity and holism') was primarily comprised of social sciences, addressed a
      wider variety of sustainability aspects including participation, equity, ethics
      and biodiversity, and more often pointed to the shortcomings of Golden Rice.
      There were little to no integration efforts between the two branches, and highly
      polarized positions arose in the clusters on 'advocacy' and 'equity and holism'.
      To explore this divide, we investigated the influences of disciplinary
      affiliations and personal values on the respective problem framings. We conclude
      that to move beyond a polarized debate, it may be fruitful to ground the Golden
      Rice discourse in facets and methods of sustainability science, with an emphasis
      on participation and integration of diverging interests.

PMID- 30220918
TI  - Engaging stakeholders in research to address water-energy-food (WEF) nexus
      challenges.
AB  - The water-energy-food (WEF) nexus has become a popular, and potentially powerful,
      frame through which to analyse interactions and interdependencies between these
      three systems. Though the case for transdisciplinary research in this space has
      been made, the extent of stakeholder engagement in research remains limited with
      stakeholders most commonly incorporated in research as end-users. Yet,
      stakeholders interact with nexus issues in a variety of ways, consequently there
      is much that collaboration might offer to develop nexus research and enhance its
      application. This paper outlines four aspects of nexus research and considers the
      value and potential challenges for transdisciplinary research in each. We focus
      on assessing and visualising nexus systems; understanding governance and capacity
      building; the importance of scale; and the implications of future change. The
      paper then proceeds to describe a novel mixed-method study that deeply integrates
      stakeholder knowledge with insights from multiple disciplines. We argue that
      mixed-method research designs-in this case orientated around a number of cases
      studies-are best suited to understanding and addressing real-world nexus
      challenges, with their inevitable complex, non-linear system characteristics.
      Moreover, integrating multiple forms of knowledge in the manner described in this
      paper enables research to assess the potential for, and processes of, scaling-up
      innovations in the nexus space, to contribute insights to policy and decision
      making.

PMID- 30220920
TI  - Valgus instability of the elbow: acute and chronic form.
AB  - There has been an increase in thrower-specific elbow injuries in recent years.
      High valgus stresses during the late cocking and acceleration phases of throwing
      need to be compensated by the flexor pronator muscles as these can exceed the
      tensile strength of the medial collateral ligament complex. Prevention of
      injuries is the priority, with a focus on strengthening, reducing throwing
      frequency, decreasing force, and promoting a technique. The spectrum of thrower
      injuries ranges from a simple sprain to complete failure of the valgus
      stabilizing factors. The medial collateral ligament can stretch, leading to
      posteromedial impingement and radiocapitellar compression forces. This in turn
      can result in arthrosis and the formation of osteophytes. Ligament failure may
      eventually occur, making it impossible for the athlete to continue their throwing
      activities. The outcome of conservative treatment with strengthening, improvement
      of technique, and relative rest is often disappointing. Direct repair may no
      longer be possible in these acute-on-chronic injuries and a reconstruction with a
      tendon graft may be necessary.

PMID- 30220921
TI  - Functional outcomes and complications of open elbow dislocations.
AB  - Background: The current study investigated the clinical outcome of open elbow
      dislocations, focusing on the influence of associated soft tissue and bone
      injury. Patients and methods: From October 2008 to August 2015, 230 patients with
      elbow dislocations were treated at the study center. Our retrospective study
      comprised 21 cases of open elbow dislocations. The mean age of patients was 49
      years (20-83 years); there were six (29%) female and 15 (71%) male patients. The
      range of motion (ROM) of the injured and uninjured elbow was measured, and the
      Mayo Elbow Performance Score (MEPS), Mayo Wrist Score (MWS), and Disability of
      Arm, Shoulder and Hand (DASH) score were assessed. Complications and revision
      surgeries were recorded. The influence of the severity of soft tissue injury (I
      degrees /II degrees  open vs. III degrees  open) and type of dislocation (simple
      vs. complex) was evaluated. Results: After a 57-month follow-up (range, 24-98
      months), the mean DASH score was 20 +/- 15, the MEPS was 82 +/- 11, and the MWS
      was 74 +/- 22. The ROM of the injured elbow was significantly decreased compared
      with the uninjured one (arc of ulnohumeral motion: 104 degrees  vs. 137 degrees ;
      p = 0.001). Patients with I degrees /II degrees  open elbow dislocations had a
      better clinical outcome according to the MEPS (86 +/- 11 vs. 76 +/- 9; p = 0.045)
      and a comparable outcome according to the DASH score (19 +/- 18 vs. 21 +/- 9; p =
      0.238). In all, 11 patients (52%) had postoperative complications and 11 patients
      underwent at least one revision surgery. Complex elbow dislocations had
      significantly more complications and revision surgeries than simple dislocations
      (77% vs. 13%; p = 0.008). Conclusion: Favorable clinical outcomes can be achieved
      after treatment of open elbow dislocations. These injuries are prone to
      neurovascular damage and complex dislocations are linked to high rates of
      complications and revision surgeries.

PMID- 30220913
TI  - Native-mimicking in vitro microenvironment: an elusive and seductive future for
      tumor modeling and tissue engineering.
AB  - Human connective tissues are complex physiological microenvironments favorable
      for optimal survival, function, growth, proliferation, differentiation,
      migration, and death of tissue cells. Mimicking native tissue microenvironment
      using various three-dimensional (3D) tissue culture systems in vitro has been
      explored for decades, with great advances being achieved recently at material,
      design and application levels. These achievements are based on improved
      understandings about the functionalities of various tissue cells, the
      biocompatibility and biodegradability of scaffolding materials, the biologically
      functional factors within native tissues, and the pathophysiological conditions
      of native tissue microenvironments. Here we discuss these continuously evolving
      physical aspects of tissue microenvironment important for human disease modeling,
      with a focus on tumors, as well as for tissue repair and regeneration. The
      combined information about human tissue spaces reflects the necessities of
      considerations when configuring spatial microenvironments in vitro with native
      fidelity to culture cells and regenerate tissues that are beyond the formats of
      2D and 3D cultures. It is important to associate tissue-specific cells with
      specific tissues and microenvironments therein for a better understanding of
      human biology and disease conditions and for the development of novel approaches
      to treat human diseases.

PMID- 30220922
TI  - Anterior shoulder dislocation and concomitant fracture of the greater tuberosity:
      Clinical and radiological results.
AB  - Background: Recurrence rates after primary traumatic shoulder dislocation are
      distinctly high. We hypothesized that concomitant isolated fractures of the
      greater tuberosity are associated with low rates of persistent instability but
      decreased range of motion. Methods: Between 2007 and 2013, 66 consecutive
      shoulders in 64 patients were treated for primary shoulder dislocation combined
      with an isolated fracture of the greater tuberosity with either a nonsurgical (48
      shoulders, 72.7%) or surgical (18 shoulders, 27.3%) treatment approach. In all,
      55 cases (83.3%) were available for clinical follow-up examination after an
      average of 59.0 +/- 20.7 months (range: 25-96 months) and of these, 48 (72.7%)
      patients consented to radiological evaluation to determine healing and position
      of the greater tuberosity. Results: The mean range of motion of the affected
      shoulder was significantly decreased by 9 degrees  of elevation (p = 0.016), 11
      degrees  of abduction (p = 0.048), 9 degrees  of external rotation in 0 degrees 
      of abduction (p = 0.005), and 10 degrees  of external rotation in 90 degrees  of
      abduction (p = 0.001), compared with the unaffected shoulder. The mean WOSI score
      was 373 +/- 486 points, the mean Constant and Murley score was 75.1 +/- 19.4
      points, and the mean Rowe score was 83 +/- 20 points. Three cases (5.5%) of re
      dislocation were reported among the cohort, all of them were due to a relevant
      trauma. Radiological evaluation revealed anatomically healed fragments in 31
      shoulders (65%), dislocation of the fragment in ten shoulders (21%), impaction
      into the humeral head in four shoulders (8%), and absorption in three shoulders
      (6%). Conclusion: A concomitant isolated fracture of the greater tuberosity leads
      to low recurrence rates along with a significant decrease in range of motion
      after primary traumatic anterior shoulder dislocation.

PMID- 30220923
TI  - Cure in metastatic breast cancer.
AB  - Oligometastatic disease characterizes a distinct subgroup of metastatic breast
      cancer patients that might benefit from different treatment strategies to achieve
      long-lasting remission and potentially cure. Those long-lasting remissions are
      reported after locoregional treatment of the primary tumor and all metastatic
      sites in several case series; however, unlike other tumor entities, prospective
      data are lacking. Furthermore, tumor eradication by excellent systemic anticancer
      therapy with novel chemotherapies and targeted agents can lead to long-term
      survival. In addition, reactivation of the host immune defense by immuno
      oncologic drugs can achieve long-lasting tumor control. So far, unfortunately,
      checkpoint inhibitors as monotherapy have led to responses only in a small
      percentage of patients with metastatic breast cancer. This short review
      summarizes available data on long-lasting remissions and potential cure in
      metastatic breast cancers. It describes and discusses data on locoregional
      treatment, chemo-, antibody- and immunotherapy and tries to select individual
      patients for whom a multidisciplinary treatment approach with curative intention
      might be an option to achieve long-term survival.

PMID- 30220925
TI  - Demystification of palliative care: what palliative care teams don't want you to
      think about them.
AB  - There is robust data that palliative care is prolonging life while there are
      still prejudices towards this discipline that have to be demystified. Patients,
      relatives and caregivers benefit from the concept of early integration of
      palliative care and therefore, palliative care should not be mainly regarded as
      end-of-life care.

PMID- 30220924
TI  - Long-term remission in advanced stage hepatocellular carcinoma? A chance for
      cure?
AB  - Liver resection, transplantation, and local ablation are potential curative
      treatment options but can only be offered to patients with early stage
      hepatocellular carcinoma (HCC). Patients with macrovascular tumor invasion and
      extrahepatic metastases are candidates for palliative systemic therapies.
      Achieving radiological complete response can be associated with long-term
      remission and excellent outcome. However, despite recent advancements in the
      medical treatment of advanced stage HCC, complete remission with available
      systemic treatment options still remains a rare event. This review summarizes
      data on radiological complete response to systemic therapies and discusses issues
      that may complicate the goal of achieving cure in advanced stage HCC.

PMID- 30220926
TI  - Current concepts and future directions in neoadjuvant chemotherapy of breast
      cancer.
AB  - Preoperative administration of chemotherapy is a widespread treatment approach in
      early stage breast cancer whenever chemotherapy is indicated in principle. In
      addition, neoadjuvant treatment is today regarded as the preferred way of
      delivering systemic therapy in triple-negative and HER2-positive breast cancer.
      While preoperative chemotherapy allows for disease downstaging and increases
      breast conservation rates, achieving pathologic complete remission (pCR) is
      usually regarded as the most pertinent aim as pCR predicts for improved long-term
      outcome in high-risk breast cancer subtypes. A multitude of clinical trials
      therefore have focused on strategies to increase pCR rates. This short review
      summarizes outcomes of selected studies investigating the addition of further
      chemotherapeutic drugs or biologically targeted agents to standard regimens and
      provides an overview of novel strategies currently under clinical evaluation.

PMID- 30220927
TI  - SABCS 2017: update on chemotherapy, targeted therapy, and immunotherapy.
AB  - In the areas of chemotherapy, targeted therapy and immunotherapy, several
      interesting and clinically relevant data were presented at the 2017 San Antonio
      Breast Cancer Symposium (SABCS). This short review focuses on dose-dense and/or
      sequential administration of adjuvant chemotherapy, provides an update on
      targeted therapies for HER2-positive and triple-negative breast cancer and
      summarizes new results in the field of immunotherapy.

PMID- 30220928
TI  - SABCS 2017: lifestyle factors, hormone receptor-positive advanced disease, liquid
      biopsies, and prognosis.
AB  - This article reviews the clinically most relevant presentations at the San
      Antonio Breast Cancer Symposium (SABCS) 2017 on the topics lifestyle factors,
      hormone receptor-positive advanced disease, liquid biopsies, and prognosis. In a
      retrospective analysis of the Women's Health Initiative Observational Study, a
      reduction in the body mass index (BMI) of at least 5% within 3 years
      significantly reduced the risk of breast cancer compared to women with a stable
      weight (HR 0.77; 95% CI 0.78-0.98). In the MONALEESA-7 trial investigating
      ribociclib or placebo in combination with endocrine therapy as first-line
      treatment in pre- and perimenopausal women with hormone receptor-positive, human
      epidermal growth factor 2 (HER2)-negative metastatic breast cancer, a
      significantly longer progression-free survival was shown for patients treated
      with ribociclib compared to the placebo group (23.8 vs. 13.0 months; HR 0.55; 95%
      CI 0.43-0.72; P < 0.001). In a pooled toxicity and efficacy analysis of elderly
      women treated with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in
      combination with an aromatase inhibitor in first-line, toxicities of higher grade
      were more common in elderly compared to younger patients, despite comparable
      efficacy. And the Clinical Treatment Score post-5 years (CTS5), accurately
      estimated the risk of late recurrence after 5 years of adjuvant endocrine
      treatment using routinely available clinical parameters.

PMID- 30220929
TI  - Post SABCS local therapy and radiology.
AB  - This year there were three interesting oral presentations and several posters
      presenting important new data regarding local therapy (surgery and radiotherapy)
      as well as radiological aspects. This minireview is a personal view of the
      clinically most relevant data in this respect with the following conclusions: A
      micrometastasis is no indication for axillary dissection. The number of involved
      sentinel lymph nodes predicts non-sentinel lymph node metastasis and should be
      taken into account regarding omitting axillary dissection. Neoadjuvant
      chemotherapy reduces the risk of non-sentinel lymph node metastasis. A 2 mm
      margin shows an optimal rate of local recurrences after breast conservation. The
      question of the correct definition for an R0 resection after neoadjuvant therapy
      remains open. We should omit radiotherapy for women with low risk ductal
      carcinoma in situ (DCIS) below 2.5 cm in size and pT1a G1 after breast
      conservation. Risk of finding invasive cancer after having a B3 biopsy is very
      low depending on the type of lesion, thus, questioning the surgical approach of
      some of these entities. The use of magnetic resonance imaging is a standard
      procedure before and after neoadjuvant therapy. Data regarding correlation
      between complete radiologic response (rCR) with pathologic complete response
      (pCR) and real tumor size are rare. For women with micrometastases or isolated
      tumor cells in the sentinel node postmastectomy radiotherapy has little benefit.
      After neoadjuvant therapy only women with ypN2 had a significant benefit of
      postmastectomy radiotherapy for local, disease-free and overall survival.

PMID- 30220930
TI  - SABCS 2017 pathology: from bench to bedside.
AB  - The 40th International San Antonio Breast Cancer Symposium offered a multifaceted
      platform for the presentation of several innovative therapeutic approaches. The
      results of these preclinical and clinical studies provided insight into the
      development of novel therapy concepts from the laboratory bench to the bedside of
      breast cancer patients. One main focus of last year's symposium was the search
      for synergisms and opportunities for collaboration between basic research
      scientists and investigators in drug development. Highlights of these topics
      included preclinical data on selective estrogen receptor covalent antagonists
      (SERCAs), the discovery of immune-modulating effects of demethylating agents as
      well as the exact characterization and risk assessment of BRCA2 mutations of
      previously unknown significance. Pathological advances aimed at the molecular
      understanding of intratumoral heterogeneity and the evolution of lobular breast
      cancer. Beyond preclinical discoveries at the molecular level, clinical studies
      provided evidence on the duration of adjuvant bisphosphonate treatment and the
      use of the EndoPredict multigenomic assay to predict response to neoadjuvant
      chemo- and endocrine therapy. The SUCCESS A study reported that the prolonged
      adjuvant administration of zoledronic acid for 5 years did not improve patient
      survival after chemotherapy. A translational analysis of the ABCSG 34 trial
      revealed that the EndoPredict multigenomic assay could identify patients who do
      not benefit from neoadjuvant endocrine or chemotherapy. These recent advances are
      likely to promote individualized breast cancer care.

PMID- 30220931
TI  - Thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a clearly defined entity of the
      thrombotic microangiopathies (TMA), a heterogeneous group of disorders
      characterized by microangiopathic hemolytic anemia with red cell fragmentation,
      thrombocytopenia and organ dysfunction due to disturbed microcirculation. TTP is
      characterized by a severe deficiency of ADAMTS13 (a disintegrin and
      metalloproteinase with a thrombospondin type 1 motif, member 13), an enzyme
      responsible for physiological cleavage of von Willebrand factor (VWF). Organ
      dysfunction can be severe and life-threatening, and immediate start of
      appropriate therapy is necessary to avoid permanent damage or death. Until
      recently, therapeutic options were limited to symptomatic measures, which were
      not standardized or based on high scientific evidence. In recent years, not only
      considerable progress has been made in better diagnosis of TTP, but also new
      therapeutic strategies have been established. Initial treatment is still based on
      plasma exchange and symptomatic measures to protect organ function, but new
      concepts (immunosuppression, targeted anti-VWF or anti-complement therapy,
      replacement with recombinant enzymes) have recently demonstrated impressive
      advantages.

PMID- 30220932
TI  - Current and evolving treatment strategies in adult immune thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an acquired autoimmune phenomenon resulting in
      low platelet count and increased bleeding risk. Goals of upfront management
      include prompt control of severe bleeding-which is rare-as well as induction and
      maintenance of a hemostatic platelet count. Thus, optimal management of ITP
      patients is often challenging and requires a highly individualized approach. Many
      patients may not suffer significant bleeding despite severe thrombocytopenia and
      the risk of toxicity associated with treatment may outweigh its benefit. Most
      patients treated with standard first-line regimen of glucocorticoids achieve an
      initial response. However, the rate of long-term remission remains low and
      multiple lines of therapy are often required. Current investigations aim at
      defining the subgroup of patients at risk of relapse and providing intensified
      risk-balanced induction regimens to improve long-term disease control. This short
      review summarizes current and emerging treatment strategies in adult ITP.

PMID- 30220933
TI  - Valuing Sets of Potential Transplants in a Kidney Paired Donation Network.
AB  - In kidney paired donation (KPD), incompatible donor-candidate pairs and non
      directed (also known as altruistic) donors are pooled together with the aim of
      maximizing the total utility of transplants realized via donor exchanges. We
      consider a setting in which disjoint sets of potential transplants are selected
      at regular intervals, with fallback options available within each proposed set in
      the case of individual donor, candidate or match failure. We develop methods for
      calculating the expected utility for such sets under a realistic probability
      model for the KPD. Exact expected utility calculations for these sets are
      compared to estimates based on Monte Carlo samples of the underlying network.
      Models and methods are extended to include transplant candidates who join KPD
      with more than one incompatible donor. Microsimulations demonstrate the
      superiority of accounting for failure probability and fallback options, as well
      as candidates joining with additional donors, in terms of realized transplants
      and waiting time for candidates.

PMID- 30220934
TI  - Conceptual Congruence in Mindfulness-Based Weight Loss Intervention Studies.
AB  - Whether one kind of mindfulness applies to all situations or only some (i.e.,
      scope) is controversial. Eating may not be an everyday behavior subsumed under
      everyday mindfulness. To rigorously test the efficacy of mindfulness-based weight
      loss interventions, researchers must use scales that measure the type of
      mindfulness manipulated by the intervention. The mixed findings of mindfulness
      based weight loss intervention studies may be related to the lack of conceptual
      congruence (i.e., the pairing of interventions and measures of the same scope).
      The aims of this systematic review were to: (a) describe the scopes of the
      mindfulness interventions and measures used in mindfulness-based weight loss
      intervention studies; and (b) compare conceptual congruence to the statistical
      significance of mindfulness and weight outcomes of each study. All articles
      published prior to December 31, 2016 were retrieved from PubMed, CINAHL,
      PsycINFO, and Embase. After screening and full-text review, eight articles were
      included in the review. Five studies paired mindfulness-based eating
      interventions with general mindfulness measures; two studies paired mindfulness
      based eating interventions with eating-specific mindfulness measures; and one
      study paired a general mindfulness intervention with a general mindfulness
      measure. There was no apparent relationship between conceptual congruence and the
      statistical significance of the mindfulness and weight outcomes. However, given
      other findings and the limitations of this review, further investigation is
      needed. In particular, future studies should include mediation analyses using
      both general and eating-specific mindfulness measures.

PMID- 30220936
TI  - Air pollutant strategies to reduce adverse health impacts and health
      inequalities: a quantitative assessment for Detroit, Michigan.
AB  - The development of air quality management (AQM) strategies provides opportunities
      to improve public health and reduce health inequalities. This study evaluates
      health and inequality impacts of alternate SO2 control strategies in Detroit, MI,
      a designated non-attainment area. Control alternatives include uniform reductions
      across sources, ranking approaches based on total emissions and health impacts
      per ton of pollutant emitted, and optimizations that meet concentration and
      health goals. Using dispersion modeling and quantitative health impact assessment
      (HIA), these strategies are evaluated in terms of ambient concentrations, health
      impacts, and the inequality in health risks. The health burden attributable to
      SO2 emissions in Detroit falls primarily among children and includes 70
      hospitalizations and 6,000 asthma-related respiratory symptom-days annually,
      equivalent to 7 disability-adjusted life years (DALYs). The health burden
      disproportionately falls on Hispanic/Latino residents, residents with less than a
      high school diploma, and foreign-born residents. Control strategies that target
      smaller facilities near exposed populations provide the greatest benefit in terms
      of the overall health burden reductions and the inequality of attributable health
      risk; conventional strategies that target the largest emission sources can
      increase inequality and provide only modest health benefits. The assessment is
      novel in using spatial analyses that account for urban scale gradients in
      exposure, demographics, vulnerability, and population health. We show that
      quantitative HIA methods can be used to develop AQM strategies that
      simultaneously meet environmental, public health, and environmental justice
      goals, advancing AQM beyond its current compliance-oriented focus.

PMID- 30220935
TI  - Methodological issues in measuring subjective well-being and quality-of-life:
      Applications to assessment of affect in older, chronically and cognitively
      impaired, ethnically diverse groups using the Feeling Tone Questionnaire.
AB  - Quality of life assessment includes measurement of positive affect. Methods
      artifacts associated with positively and negatively worded items can manifest as
      negative items loading on a second factor, despite the conceptual view that the
      items are measuring one underlying latent construct. Negatively worded items may
      elicit biased responses. Additionally, item-level response bias across ethnically
      diverse groups may compromise group comparisons. The aim was to illustrate
      methodological approaches to examining method factors and measurement equivalence
      in an affect measure with 9 positively and 7 negatively worded items: The Feeling
      Tone Questionnaire (FTQ). The sample included 4,960 non-Hispanic White, 1,144 non
      Hispanic Black, and 517 Hispanic community and institutional residents receiving
      long-term supportive services. The mean age was 82 (s.d.=11.0); 73% were female.
      Two thirds were cognitively impaired. Methods effects were assessed using
      confirmatory factor analyses (CFA), and reliability with McDonald's omega and
      item response theory (IRT) generated estimates. Measurement equivalence was
      examined using IRT-based Wald tests. Methods effects associated with negatively
      worded items were observed; these provided little IRT information, and as a
      composite evidenced lower reliability. Both 13 and 9 item positive affect scales
      performed well in terms of model fit, reliability, IRT information, and evidenced
      little differential item functioning of high magnitude or impact. Both CFA and
      IRT approaches provided complementary methodological information about scale
      performance. The 9-item affect scale based on the FTQ can be recommended as a
      brief quality-of-life measure among frail and cognitively impaired individuals in
      palliative and long-term care settings.

PMID- 30220938
TI  - Migration and the Multi-Dimensional Well-Being of Elderly Persons in Georgia.
AB  - High rates of migration coupled with low formal social protection provisions may
      place many members of the elderly Georgian population in precarious living
      conditions that promote vulnerability and limit well-being achievement. This
      potential connection has been poorly explored in past literature, however,
      suggesting a need to better assess how the migration of an adult child may
      influence the multidimensional well-being of the elderly in Georgia. Using a
      novel dataset comprising 2202 elderly individuals across all regions of Georgia
      (excepting the territories of Abkhazia and South Ossetia), this paper proposes a
      multidimensional well-being index that has been specifically designed to
      encompass the unique resources and constraints faced by elderly individuals in
      different age cohorts. Following the construction of a multidimensional well
      being index-comprised of domains including physical health and independence,
      housing well-being, social well-being, and emotional well-being-the outcomes of
      elderly individuals are compared by age and the presence/absence of adult
      children due to migration. Findings suggest that the migration status of an
      elderly person's adult children is related to the attainment of well-being.
      Elderly individuals with a migrant child are more likely to attain well-being in
      physical health as well as in the overall multidimensional well-being index.

PMID- 30220937
TI  - Bottom Up Ethics - Neuroenhancement in Education and Employment.
AB  - Neuroenhancement involves the use of neurotechnologies to improve cognitive,
      affective or behavioural functioning, where these are not judged to be clinically
      impaired. Questions about enhancement have become one of the key topics of
      neuroethics over the past decade. The current study draws on in-depth public
      engagement activities in ten European countries giving a bottom-up perspective on
      the ethics and desirability of enhancement. This informed the design of an online
      contrastive vignette experiment that was administered to representative samples
      of 1000 respondents in the ten countries and the United States. The experiment
      investigated how the gender of the protagonist, his or her level of performance,
      the efficacy of the enhancer and the mode of enhancement affected support for
      neuroenhancement in both educational and employment contexts. Of these, higher
      efficacy and lower performance were found to increase willingness to support
      enhancement. A series of commonly articulated claims about the individual and
      societal dimensions of neuroenhancement were derived from the public engagement
      activities. Underlying these claims, multivariate analysis identified two social
      values. The Societal/Protective highlights counter normative consequences and
      opposes the use enhancers. The Individual/Proactionary highlights opportunities
      and supports use. For most respondents these values are not mutually exclusive.
      This suggests that for many neuroenhancement is viewed simultaneously as a source
      of both promise and concern.

PMID- 30220940
TI  - Explaining Children's Life Outcomes: Parental Socioeconomic Status, Intelligence
      and Neurocognitive Factors in a Dynamic Life Cycle Model.
AB  - The goal of the present paper is to introduce a dynamic life cycle model that
      explains the reproduction of wealth and health over generations by introducing
      knowledge from cognitive neuroscience into the existing knowledge from the
      socioeconomic literature. The socioeconomic literature successfully identified
      the major role of socioeconomic status of parents, both as a direct and indirect
      effect, in the shaping and intergenerational reproduction of wealth and health.
      Furthermore, the importance of cognitive abilities as actor in this process has
      been widely studied in socioeconomic literature. A third factor that has been
      identified by the socioeconomic discipline is the so-called non-cognitive
      capabilities. This category, however, lacks a clear definition and seems to be a
      catchall for a collection of factors. Within the repository of these non
      cognitive capabilities the construct of executive functions is an interesting and
      important contribution from cognitive neuroscience. The multidimensional
      construct of executive functioning or cognitive control (i.e. planning and
      formulation of objectives) and monitoring processes (i.e. influences the
      execution of these goals) is a valuable addition to a framework on reproduction
      of wealth and health over generations, because executive functions are sensitive
      to training. Merging insights of the socioeconomic literature and cognitive
      neuroscience in a life cycle model opens the opportunity of educational
      initiatives with regard to executive functions to break the intergenerational
      reproduction of poverty and deprivation.

PMID- 30220941
TI  - Testing Longitudinal Relationships between Internet Addiction and Well-Being in
      Hong Kong Adolescents: Cross-Lagged Analyses Based on three Waves of Data.
AB  - Using a panel design, this study examined the prospective relationships between
      Internet addiction and life satisfaction as well as hopelessness in a
      representative sample of Hong Kong adolescents. Starting from 2009/10 academic
      year, 3328 Secondary 1 students in 28 secondary schools in Hong Kong participated
      in this longitudinal study (Mean age = 12.59 years; SD = 0.74 years). All
      participants responded to a questionnaire that includes the Internet Addiction
      Test, Life Satisfaction Scale, and Hopelessness Scale on a yearly basis. Cross
      lagged analyses based on three waves of data collected during three junior
      adolescent years showed that Internet addiction measured at Time 1 predicted poor
      life satisfaction and hopelessness at Time 2, but not vice versa. Similarly,
      Internet addiction at Time 2 predicted low life satisfaction at Time 3, and the
      cross-lagged effects of life satisfaction and hopelessness on Internet addiction
      from Time 2 to Time 3 remained non-significant. The findings support the thesis
      that poor personal well-being in adolescents is the consequence rather than the
      cause of Internet addictive behaviors. To improve quality of life and prevent
      suicidality in adolescents, strategies that help reduce addictive behaviors
      related to the Internet should be considered.

PMID- 30220939
TI  - Application of the Human Well-Being Index to Sensitive Population Divisions: A
      Children's Well-Being Index Development.
AB  - The assessment of community well-being is critical as an end-point measure that
      will facilitate decision support and assist in the identification of sustainable
      solutions to address persistent problems. While the overall measure is important,
      it is equally vital to distinguish variations among groups within the population
      who may be impacted in a different manner. The U.S. Environmental Protection
      Agency (US EPA) developed the Human Well-Being Index (HWBI), as a way of
      measuring these outcomes and assessing community characteristics. The HWBI
      approach produces a suite of indicators, domains and a final composite index
      appropriate for characterizing well-being of a population. While generalized
      approaches are needed, it is important to also recognize variations in well-being
      across community enclaves. This paper presents an adaption of the HWBI for child
      populations to test the applicability of the index framework to specific
      community enclaves. First, an extensive literature review was completed to ensure
      the theoretical integrity of metric and indicator substitutions from the original
      HWBI framework. Metric data were then collected, refined, imputed where necessary
      and evaluated to confirm temporal and spatial availability. A Children's Well
      Being Index (CWBI) value, representing the same indicators and domains of well
      being as the original HWBI, was calculated for the population under age 18 across
      all US counties for 2011. Implications of this research point to an effective,
      holistic end-point measure that can be tracked over time. Similarly, there is
      great potential for the application of the original HWBI method to other
      statistical population segments within the greater US population. These
      adaptations could help identify and close gaps in equity of resource distribution
      among these groups.

PMID- 30220942
TI  - A parallel fluid-solid coupling model using LAMMPS and Palabos based on the
      immersed boundary method.
AB  - The study of viscous fluid flow coupled with rigid or deformable solids has many
      applications in biological and engineering problems, e.g., blood cell transport,
      drug delivery, and particulate flow. We developed a partitioned approach to solve
      this coupled Multiphysics problem. The fluid motion was solved by Palabos
      (Parallel Lattice Boltzmann Solver), while the solid displacement and deformation
      was simulated by LAMMPS (Large-scale Atomic/Molecular Massively Parallel
      Simulator). The coupling was achieved through the immersed boundary method (IBM).
      The code modeled both rigid and deformable solids exposed to flow. The code was
      validated with the Jeffery orbits of an ellipsoid particle in shear flow, red
      blood cell stretching test, and effective blood viscosity flowing in tubes. It
      demonstrated essentially linear scaling from 512 to 8192 cores for both strong
      and weak scaling cases. The computing time for the coupling increased with the
      solid fraction. An example of the fluid-solid coupling was given for flexible
      filaments (drug carriers) transport in a flowing blood cell suspensions,
      highlighting the advantages and capabilities of the developed code.

PMID- 30220944
TI  - Rethinking the Negativity Bias.
AB  - The negativity bias is a broad psychological principle according to which the
      negative is more causally efficacious than the positive. Bad, as it is often put,
      is stronger than good. The principle is widely accepted and often serves as a
      constraint in affective science. If true, it has significant implications for
      everyday life and philosophical inquiry. In this article, I submit the negativity
      bias to its first dose of philosophical scrutiny and argue that it should be
      rejected. I conclude by offering some alternative hedonic hypotheses that survive
      the offered arguments and may prove fruitful.

PMID- 30220943
TI  - On Deflationary Accounts of Human Action Understanding.
AB  - A common deflationary tendency has emerged recently in both philosophical
      accounts and comparative animal studies concerned with how subjects understand
      the actions of others. The suggestion emerging from both arenas is that the
      default mechanism for understanding action involves only a sensitivity to the
      observable, behavioural (non-mental) features of a situation. This kind of 'smart
      behaviour reading' thus suggests that, typically, predicting or explaining the
      behaviour of conspecifics does not require seeing the other through the lens of
      mental state attribution. This paper aims to explore and assess this deflationary
      move. In S1 I clarify what might be involved in a smart behaviour reading account
      via looking at some concrete examples. Then in S2 I critically assess the
      deflationary move, arguing that, at least in the human case, it would in fact be
      a mistake to assume that our default method of action understanding proceeds
      without appeal to mental state attribution. Finally in S3 I consider briefly how
      the positive view proposed here relates to discussions about standard two-system
      models of cognition.

PMID- 30220945
TI  - How to Measure Moral Realism.
AB  - In recent years an increasing number of psychologists have begun to explore the
      prevalence, causes and effects of ordinary people's intuitions about moral
      realism. Many of these studies have lacked in construct validity, i.e., they have
      failed to (fully or exclusively) measure moral realism. My aim in this paper
      accordingly is to motivate and guide methodological improvements. In analysis of
      prominent existing measures, I develop general recommendations for overcoming ten
      prima facie serious worries about research on folk moral realism. G1 and G2
      require studies' answer choices to be as metaethically comprehensive as
      methodologically feasible. G3 and G4 prevent fallacious inferences from
      intuitions about related debates. G5 and G6 limit first-order moral and epistemic
      influences. G7 address studies' instructions. And G8 and G9 suggest tests of
      important psychological presuppositions.

PMID- 30220946
TI  - Age-Related Chromosomal Aberrations in Patients with Diffuse Large B-Cell
      Lymphoma: An In Silico Approach.
AB  - Background: In diffuse large B-cell lymphoma (DLBCL), chromosomal aberrations are
      known to increase with advancing age. Our study aims to determine if there are
      other genetic aberrations associated with DLBCL based on age. Methods: Using the
      Mitelman Database of Genetic Aberrations, we were able to find 749 cases of DLBCL
      with genomic aberrations with a median age of 62 years. Patients with DLBCL
      chromosomal aberration analysis results were divided into four groups based on
      age (0 - 30, 31 - 50, 51 - 70, > 71 years) and examined by chi-square analysis
      and Mantel-Cox for survival analysis. Results: Ten aberrations were found to be
      significant with a particular age range: t(2;3), trisomy 19p13, trisomy 18q21,
      trisomy 3, trisomy 7, trisomy 14, trisomy 16, trisomy 18, monosomy 3 and monosomy
      11, and survival ranged from 7 to 25 months. Conclusion: This suggests that
      patients with DLBCL are likely to accumulate specific translocations depending on
      their age at the onset of DLBCL.

PMID- 30220947
TI  - Clinicopathological Features of Metastatic Gastric Tumors Originating From Breast
      Cancer: Analysis of Eleven Cases.
AB  - Background: Metastatic gastric tumor originating from breast cancer (MGTBC) is
      rare. Endoscopically, gastric cancer (GC)-like lesions and submucosal tumors
      (SMT) are the features of MGTBC. Their clinicopathological characteristics are
      currently uncertain. We analyzed the clinicopathological characteristics of 11
      patients with MGTBC to better understand the disease progression and thereby
      improve early detection methods. Methods: From 2006 to 2016, 11 patients with
      MGTBC diagnosed by esophagogastroduodenoscopy (EGD) were included. Results: All
      11 patients were women, with a median age of 57 years. Histological examination
      revealed six cases with solid tubular components and five cases with invasive
      lobular carcinoma components. Melena was the most common symptom; however,
      asymptomatic cases were also common. Seven and four cases had GC-like lesions and
      SMTs, respectively. Six of the seven cases had GC-like lesions with peritoneal
      metastasis, whereas none of the four SMT cases had peritoneal metastasis (P =
      0.015). The median overall survival (OS) in all cases was 26 months (range, 1 -
      42 months). OS in cases treated with chemotherapy after a diagnosis of gastric
      metastases was significantly better than that in those treated without
      chemotherapy (P = 0.047). One patient showed gradual transformation from an SMT
      type lesion to a Borrmann type 4-like appearance. Conclusions: MGTBC is a rare
      occurrence; however, it should be considered when gastric tumors, especially GC
      like lesions in patients with a medical history of breast cancer are found.
      Patients with breast cancer, especially invasive lobular carcinoma, should
      undergo screening EGD regularly to detect gastric metastases early and receive
      chemotherapy to obtain good outcomes.

PMID- 30220948
TI  - Adenocarcinoma of Lung and Bronchial Carcinoid Presenting as Double Synchronous
      Primary Lung Cancer: A Case Report and Review of Literature.
AB  - Recent advances in imaging techniques led to an increase in the incidence of
      synchronous and metachronous primary lung cancers due to early detection.
      Management of these patients is challenging and prognosis depends on the stage of
      the tumor at initial diagnosis and histological type. A 68-year-old African
      American male patient with medical history of hypertension and diabetes mellitus
      presented to our emergency department with right sided chest pain, worsening
      dyspnea and dry cough of 2-week duration. He also reported significant weight
      loss and was a smoker with 25 pack-years smoking history. Chest radiology showed
      a large right pleural effusion. Subsequent thoracentesis and fluid analysis
      revealed a lymphocytic exudate. Patient underwent bronchoscopy with findings of
      an endobronchial lesion in the left lower bronchus. Microscopic analysis of the
      biopsy specimen showed a well differentiated carcinoid. It was decided to proceed
      with VATS and pleural biopsy as part of workup for unexplained exudative pleural
      effusion. Multiple pleural nodules were detected during the procedure and biopsy
      of these nodules revealed adenocarcinoma of lung. He was evaluated by Oncology
      and underwent palliative chemotherapy. The association of carcinoid with
      adenocarcinoma of lung was infrequently reported in the past. This case also
      highlights the importance of additional diagnostic workup for primary when the
      diagnosed malignancy does not explain the clinical presentation.

PMID- 30220949
TI  - The First Report of Small Cell Cancer of the Uvula Presenting With Ectopic
      Adrenocorticotropic Hormone Syndrome.
AB  - Small cell carcinoma (SmCC) of the head and neck is a rare occurrence. We herein
      present a case of a 62-year-old female who was diagnosed with small cell cancer
      of the uvula. The patient developed increased body swelling, elevated blood
      pressure, persistent hypokalemia and new onset diabetes mellitus. Further workup
      confirmed a diagnosis of Cushing's syndrome secondary to ectopic
      adrenocorticotropic hormone (ACTH) production. To our knowledge, this is only the
      second case of SmCC of the uvula described in literature, and the first
      associated with any paraneoplastic syndrome. By reporting this case, we aim to
      characterize the tumor clinical course and highlight the aggressive nature of its
      growth.

PMID- 30220950
TI  - DNA Damage Repair (DDR) Mutations and the Utility of High-Risk Genetics Clinics
      in Metastatic Castration-Refractory Prostate Cancer (mCRPC).
AB  - Germline pathogenic variants (PVs) in DNA-repair genes have garnered increasing
      attention in metastatic prostate cancer, and more patients are having somatic and
      germline DNA testing performed. Interpretation of germline DNA testing is a novel
      challenge for many clinicians, and the results of germline DNA-repair gene
      testing have significant implications for men with advanced prostate cancer and
      their children and siblings. Here, we report the case of a man with metastatic
      castration-refractory prostate cancer and a pathogenic, germline BRCA2 variant.
      We discuss the significance of his referral to a high-risk genetics clinic and
      the unique targeted therapy that he responded to.

PMID- 30220951
TI  - A Case of Recurrent Pregnancy-Induced Adult Onset Familial Hemophagocytic
      Lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal disease
      primarily of children, characterized by a severe hyperinflammatory state. We
      describe a case of adult onset familial HLH with a novel exon 19, c.1607G>T
      (p.Arg536Leu) heterozygous mutation of the UNC13D gene in a 40-year-old woman who
      developed HLH during her first and second pregnancies, both episodes occurring
      during the first trimester. Our patient was treated successfully both times with
      HLH-94 protocol following spontaneous abortions and is currently in the process
      of getting a bone marrow transplant. We also discuss pregnancy as a potential
      trigger for late onset familial HLH.

PMID- 30220952
TI  - The current and emerging sources of technical lignins and their applications.
AB  - Technical lignins are bulk feedstocks. They are generated as byproducts from
      pulping or cellulosic ethanol production. Since lignin undergoes significant
      structural changes in the chemical and physical treatments, all technical lignins
      are unique in terms of chemical structure, molecular weight, polydispersity, and
      impurity profile. Kraft lignin is potentially the largest source of technical
      lignin as new isolation technologies have been implemented on industrial scale in
      recent years. Lignosulfonate has been an integral product in sulfite pulping
      biorefinery. It has a well-established market in construction industry.
      Organosolv-like lignin production is increasing as cellulosic ethanol has been
      promoted as the substitute of fossil fuel. It may have unique applications
      because it has low molecule weight and is free from sulfur. Technical lignin
      application is expected to expand as the characteristics are improved with
      fractionation or chemical modification. The application of technical lignin has
      been focusing on developing products equivalent to those made by petroleum
      chemicals. The recent development in technical lignin supply should increase its
      market share as additives in polyurethanes and as the substitute of phenol
      formaldehyde adhesives. Quality improvement of technical lignin may also
      encourage the study of lignin as an alternative feedstock for carbon fiber. In
      addition, technical lignin depolymerization has been extensively explored to
      provide renewable aromatic chemicals. Starting from controlled pyrolysis and
      thermal liquefaction as the baseline technologies, many different chemical
      depolymerization have been invented with a wide range of underlying chemical
      principles.

PMID- 30220953
TI  - Topological Data Analysis of Single-Trial Electroencephalographic Signals.
AB  - Epilepsy is a neurological disorder that can negatively affect the visual, audial
      and motor functions of the human brain. Statistical analysis of
      neurophysiological recordings, such as electroencephalogram (EEG), facilitates
      the understanding and diagnosis of epileptic seizures. Standard statistical
      methods, however, do not account for topological features embedded in EEG
      signals. In the current study, we propose a persistent homology (PH) procedure to
      analyze single-trial EEG signals. The procedure denoises signals with a weighted
      Fourier series (WFS), and tests for topological difference between the denoised
      signals with a permutation test based on their PH features persistence landscapes
      (PL). Simulation studies show that the test effectively identifies topological
      difference and invariance between two signals. In an application to a single
      trial multichannel seizure EEG dataset, our proposed PH procedure was able to
      identify the left temporal region to consistently show topological invariance,
      suggesting that the PH features of the Fourier decomposition during seizure is
      similar to the process before seizure. This finding is important because it could
      not be identified from a mere visual inspection of the EEG data and was in fact
      missed by earlier analyses of the same dataset.

PMID- 30220954
TI  - DNA-Directed Fluorescence Switching of Silver Clusters.
AB  - Silver clusters with ?30 atoms are molecules with diverse electronic spectra and
      wide-ranging emission intensities. Specific cluster chromophores form within DNA
      strands, and we consider a DNA scaffold that transforms a pair of silver
      clusters. This ~20-nucleotide strand has two components, a cluster domain (S1)
      that stabilizes silver clusters and a recognition site (S2) that hybridizes with
      complementary oligonucleotides (S2C). The single-stranded S1-S2 exclusively
      develops clusters with violet absorption and low emission. This conjugate
      hybridizes with S2C to form S1-S2:S2C, and the violet chromophore transforms to a
      fluorescent counterpart with lambdaex ~ 490 nm/lambdaem ~ 550 nm and with ~100
      fold stronger emission. Our studies focus on both the S1 sequence and structure
      that direct this violet -> blue-green cluster transformation. From the sequence
      perspective, C4X sequences with X = adenine, thymine, and/or guanine favor the
      blue-green cluster, and the specificity of the binding site depends on three
      factors: the number of C4X repeats, the identity of the X nucleobase, and the
      number of contiguous cytosines. A systematic series of oligonucleotides
      identified the optimal S1 sequence C4AC4T and discerned distinct roles for the
      adenine, thymine, and cytosines. From the structure perspective, two factors
      guide the conformation of the C4AC4T sequence: hybridization with the S2C
      complement and coordination by the cluster adduct. Spectroscopic and
      chromatographic studies show that the single-stranded C4AC4T is folded by its
      blue-green cluster adduct. We propose a structural model in which the two C4X
      motifs within C4AC4T are cross-linked by the encapsulated cluster. These studies
      suggest that the structures of the DNA host and the cluster adduct are
      interdependent.

PMID- 30220955
TI  - Enhanced Electrochemical Stability of Molten Li Salt Hydrate Electrolytes by the
      Addition of Divalent Cations.
AB  - Water can be an attractive solvent for Li-ion battery electrolytes owing to
      numerous advantages such as high polarity, nonflammability, environmental
      benignity, and abundance, provided that its narrow electrochemical potential
      window can be enhanced to a similar level to that of typical nonaqueous
      electrolytes. In recent years, significant improvements in the electrochemical
      stability of aqueous electrolytes have been achieved with molten salt hydrate
      electrolytes containing extremely high concentrations of Li salt. In this study,
      we investigated the effect of divalent salt additives (magnesium and calcium
      bis(trifluoromethanesulfonyl)amides) in a molten salt hydrate electrolyte (21 mol
      kg-1 lithium bis(trifluoromethanesulfonyl)amide) on the electrochemical stability
      and aqueous lithium secondary battery performance. We found that the
      electrochemical stability was further enhanced by the addition of the divalent
      salt. In particular, the reductive stability was increased by more than 1 V on
      the Al electrode in the presence of either of the divalent cations. Surface
      characterization with X-ray photoelectron spectroscopy suggests that a
      passivation layer formed on the Al electrode consists of inorganic salts (most
      notably fluorides) of the divalent cations and the less-soluble solid electrolyte
      interphase mitigated the reductive decomposition of water effectively. The
      enhanced electrochemical stability in the presence of the divalent salts resulted
      in a more-stable charge-discharge cycling of LiCoO2 and Li4Ti5O12 electrodes.

PMID- 30220957
TI  - Quasi-Qualitative Evaluation of Progressive Counting in Secure Accommodation in
      Scotland: an Exploratory Cluster Case Study.
AB  - This was the first study to introduce a brief exposure therapy, within a trauma
      informed phase approach, into a secure facility in Scotland. An exploratory
      cluster case study was used to identify the perceptions of the first three youth
      who completed Progressive Counting (PC), a novel approach to brief exposure,
      within the Fairy Tale Model. The youth and their newly trained therapist received
      a semi-structured interview at 3 months following the completion of therapy. In
      depth interviews involving rating scales and open-ended questions were conducted
      by telephone and digitally recorded. A quasi-qualitative approach was used to
      analyze data. Independent ratings by two researchers checked for inter-rater
      reliability. A retrospective expert rating was provided for treatment fidelity.
      Youth reported a range of gains in relation to program objectives including
      reduced distress and putting trauma into the past. Challenges of implementation
      are discussed. More rigorous evaluation of PC, including randomized control
      trials, is needed before PC can be recommended as a treatment of choice.

PMID- 30220956
TI  - Equine Facilitated Therapy for Complex Trauma (EFT-CT).
AB  - Emerging research suggests that Equine Facilitated Psychotherapy (EFP) may be
      beneficial for traumatized youth. In addition, complex trauma (i.e., multiple
      and/or prolonged developmentally adverse traumatic events which are typically
      interpersonal in nature) treatment research is still growing and there is a need
      for the development and examination of novel treatments for youth with complex
      trauma histories. The current article describes a promising EFP model for this
      population called Equine Facilitated Therapy for Complex Trauma (EFT-CT). EFT-CT
      embeds EFP practices within Attachment, Regulation and Competency (ARC), an
      extant evidence-based complex trauma treatment framework for children and
      adolescents. The authors provide three case studies using both observational data
      provided by clinicians, as well as longitudinal measures of psychosocial
      functioning, to illustrate the potential promise of EFT-CT. The article concludes
      with a discussion about implications for EFP treatment and research.

PMID- 30220958
TI  - Affective Personality Traits in Olfactory Dysfunction: the Role of Dysthymia and
      Arousal.
AB  - Introduction: Olfactory dysfunction can have a negative impact on emotional well
      being. The aim of the present study was to examine associations between olfactory
      deficits and two affective personality characteristics (trait anxiety/trait
      depression). Methods: A questionnaire study was conducted with a total of 116
      participants (33 classified as anosmic, 40 as hyposmic, and 39 as normosmic). All
      participants gave self-reports on two facets of trait depression (dysthymia,
      euthymia) and trait anxiety (arousal, worrying). Due to the fact that in all
      three groups, trait depression and anxiety were substantially correlated,
      analyses of covariance were conducted. Results: After controlling for trait
      depression, anosmic and hyposmic patients showed lower trait arousal compared to
      normosmic controls (partial eta2 = .05). After controlling for trait anxiety,
      patients scored higher on dysthymia (partial eta2 = .06). Conclusions: This study
      underlines the importance of statistically isolating specific associations
      between each of these affective personality characteristics and olfactory
      dysfunction. Implications: The present findings suggest that olfactory
      dysfunction can have opposite effects on facets of trait depression and trait
      anxiety.

PMID- 30220959
TI  - Honest People Tend to Use Less-Not More-Profanity: Comment on Feldman et al.'s
      (2017) Study 1.
AB  - This article shows that the conclusion of Feldman et al.'s (2017) Study 1 that
      profane individuals tend to be honest is most likely incorrect. We argue that
      Feldman et al.'s conclusion is based on a commonly held but erroneous assumption
      that higher scores on Impression Management Scales, such as the Lie Scale, are
      associated with trait dishonesty. Based on evidence from studies that have
      investigated (1) self-other agreement on Impression Management Scales, (2) the
      relation of Impression Management Scales with personality variables, and (3) the
      relation of Impression Management Scales with objective measures of cheating, we
      show that high scores on Impression Management Scales are associated with high
      instead of low-trait honesty when measured in low-stakes conditions. Furthermore,
      using two data sets that included an "I never swear" item, we show that profanity
      use is negatively related to other reports of HEXACO honesty-humility and
      positively related to actual cheating.

PMID- 30220960
TI  - Laypersons' Beliefs and Intuitions About Free Will and Determinism: New Insights
      Linking the Social Psychology and Experimental Philosophy Paradigms.
AB  - We linked between the social psychology and experimental philosophy paradigms for
      the study of folk intuitions and beliefs regarding the concept of free will to
      answer three questions: (1) What intuitions do people have about free will and
      determinism? (2) Do free will beliefs predict differences in free will and
      determinism intuitions? and (3) Is there more to free will and determinism than
      experiencing certainty or uncertainty about the nature of the universe? Overall,
      laypersons viewed the universe as allowing for human indeterminism, and they did
      so with certainty. Examining intuitions of prosociality, future orientation,
      learning, meaningfulness, human uniqueness, and well-being, ratings were highest
      in the indeterministic universe condition and lowest in the deterministic
      universe condition, both significantly different from the uncertain universe
      condition. Participants' free will beliefs had only weak impact on realism,
      happiness, and learning intuitions but did not reverse the general intuition
      favoring indeterminism and showed no impact on other intuitions.

PMID- 30220962
TI  - Employment Outcomes From a Randomized Controlled Trial of Two Employment
      Interventions With Homeless Youth.
AB  - Objective: Limited research exists on how employment interventions contribute to
      employment outcomes for homeless youth. This study examines the comparative
      efficacy of 2 interventions-Social Enterprise Intervention (SEI) and Individual
      Placement and Support (IPS)-provided to homeless youth with mental illness in a
      randomized controlled trial. Method: Participants were recruited from 1 homeless
      youth agency in Los Angeles, CA, and randomized to the SEI (n = 36) or IPS (n =
      36) conditions. Over 20 months, SEI participants received 4 SEI components, and
      IPS participants received IPS services based on 8 principles. Data were collected
      at baseline and follow-up for the primary employment outcome (paid employment)
      and 5 secondary employment outcomes. Results: Over 20 months, 39% of SEI
      participants and 32% of IPS participants reported any paid employment. Across
      both groups, participants who reported working at baseline had nearly 8 times the
      odds of working at follow-up (OR = 7.91, p < 0.05). No statistically significant
      differences were detected across the full sample or between groups on the primary
      or secondary employment outcomes. Conclusions: Future effectiveness research is
      needed to compare the long-term employment outcomes of the SEI and IPS with a
      more heterogeneous sample of homeless youth using customized homelessness support
      services and more nuanced employment outcomes.

PMID- 30220961
TI  - The dosimetric effects of limited elective nodal irradiation in volumetric
      modulated arc therapy treatment planning for locally advanced non-small cell lung
      cancer.
AB  - Objective: Contemporary radiotherapy guidelines for locally advanced non-small
      cell lung carcinoma (LA-NSCLC) recommend omitting elective nodal irradiation,
      despite the fact that evidence supporting this came primarily from older reports
      assessing comprehensive nodal coverage using 3D conformal techniques. Herein, we
      evaluated the dosimetric implications of the addition of limited elective nodal
      irradiation (LENI) to standard involved field irradiation (IFI) using volumetric
      modulated arc therapy (VMAT) planning. Method: Target volumes and organs-at-risk
      (OARs) were delineated on CT simulation images of 20 patients with LA-NSCLC. Two
      VMAT plans (IFI and LENI) were generated for each patient. Involved sites were
      treated to 60 Gy in 30 fractions for both IFI and LENI plans. Adjacent uninvolved
      nodal regions, considered high risk based on the primary tumor site and extent of
      nodal involvement, were treated to 51 Gy in 30 fractions in LENI plans using a
      simultaneous integrated boost approach. Results: All planning objectives for PTVs
      and OARs were achieved for both IFI and LENI plans. LENI resulted in
      significantly higher esophagus Dmean (15.3 vs. 22.5 Gy, p < 0.01), spinal cord
      Dmax (34.9 vs. 42.4 Gy, p = 0.02) and lung Dmean (13.5 vs. 15.9 Gy, p = 0.02),
      V20 (23.0 vs. 27.9%, p = 0.03), and V5 (52.6 vs. 59.4%, p = 0.02). No differences
      were observed in heart parameters. On average, only 32.2% of the high-risk nodal
      volume received an incidental dose of 51 Gy when untargeted in IFI plans.
      Conclusion: The addition of LENI to VMAT plans for LA-NSCLC is feasible, with
      only modestly increased doses to OARs and marginal expected increase in
      associated toxicity.

PMID- 30220963
TI  - Selecting suitable chemotherapies for PD-1/PD-L1 blockade to optimize the tumor
      immune microenvironment.

PMID- 30220964
TI  - Balance deficits in long-term pediatric ALL survivors.

PMID- 30220965
TI  - Tumor cell density regulates matrix metalloproteinases for enhanced migration.
AB  - Matrix metalloproteinases (MMPs) may play a critical role in metastatic cancers,
      yet multiple human clinical trials targeting MMPs have surprisingly failed.
      Cancer cell density changes dramatically during the early growth of a primary
      tumor and during the early seeding steps of secondary tumors and has been
      implicated in playing an important role in regulating metastasis and drug
      resistance. This study reveals that the expression of MMPs is tightly regulated
      by local tumor cell density through the synergistic signaling mechanism of
      Interleukin 6 (IL-6) and Interleukin 8 (IL-8) via the JAK2/STAT3 complex. Local
      tumor cell density also plays a role in the responsiveness of cells to matrix
      metalloproteinases inhibitors (MMPI), such as Batimastat, Marimastat, Bryostatin
      I, and Cipemastat, where different migratory phenotypes are observed in low and
      high cell density conditions. Cell density-dependent MMP regulation can be
      directly targeted by the simultaneous inhibition of IL-6 and IL-8 receptors via
      Tocilizumab and Reparixin to significantly decrease the expression of MMPs in
      mouse xenograft models and decrease effective metastasis. This study reveals a
      new strategy to decrease MMP expression through pharmacological intervention of
      the cognate receptors of IL-6 and IL-8 to decrease metastatic capacity of tumor
      cells.

PMID- 30220966
TI  - Circulating tumor DNA as a marker of treatment response in BRAF V600E mutated non
      melanoma solid tumors.
AB  - Purpose: We evaluated longitudinal tracking of BRAF V600E in circulating cell
      free DNA (cfDNA) as a marker of treatment response to BRAF inhibitor (BRAFi)
      combination therapies in non-melanoma solid tumors included in the Copenhagen
      Prospective Personalized Oncology (CoPPO) program. Experimental design: Patients
      with BRAF V600E-mutated tumors were treated with combination therapies including
      BRAFi. Quantification of mutant cfDNA from plasma was determined and correlated
      to clinical outcomes. Exome sequencing was performed to identify possible
      resistance mutations. Results: Twenty-three patients had BRAF-mutated tumors out
      of 455 patients included in CoPPO and 17 started BRAFi combination (EGFRi/MEKi)
      therapy. Tumor responses were achieved in 8 out of 16 evaluable patients and the
      median overall- and progression-free survival (OS and PFS) was 15 and 4.8 months,
      respectively. Longitudinal measurements of BRAF V600E-mutant cfDNA indicated
      disease progression prior to radiological evaluation and a reduction in the
      mutant fraction of more than 50% after 4 and 12 weeks of therapy was associated
      with a significantly longer PFS (p=0.003 and p=0.029) and OS (p=0.029 and
      p=0.017). Furthermore, the baseline mutant fraction and total level of cfDNA
      positively correlated with tumor burden (p=0.026 and p=0.024). Finally, analysis
      of cfDNA at progression revealed novel mutations potentially affecting the MAPK
      pathway. Conclusion: BRAFi combination therapies showed a response rate of 50% in
      BRAF V600E-mutated non-melanoma tumors. The fraction of BRAF-mutant cfDNA
      represent a sensitive indicator for clinical outcomes with plasma collected at
      week 4 and 12 as crucial time points for monitoring response and disease
      progression.

PMID- 30220967
TI  - Chromatin remodeling protein HELLS is upregulated by inactivation of the RB-E2F
      pathway and is nonessential for osteosarcoma tumorigenesis.
AB  - Osteosarcoma is the most common primary bone malignancy in children and
      adolescents. Among the various molecular mechanisms implicated in
      osteosarcomagenesis, the RB-E2F pathway is of particular importance as virtually
      all cases of osteosarcoma display alterations in the RB-E2F pathway. In this
      study, we examined the transcription factor E2F family members that are
      associated with increased malignancy in Rb1-null osteosarcoma tumors. Using
      genetically engineered mouse models of osteosarcoma, we found that loss of
      activator E2Fs, E2F1 and E2F3, significantly delays tumor progression and
      increases the overall survival of the p53/Rb1-deficient osteosarcoma mouse model.
      We also studied the role of helicase, lymphoid specific (HELLS), a chromatin
      remodeling protein identified as a critical downstream effector of the RB-E2F
      signaling pathway in various cancers. In this study, we confirmed that the RB-E2F
      pathway directly regulates HELLS gene expression. We also found that HELLS mRNA
      is upregulated and its protein overexpressed in osteosarcoma. Using loss-of
      function assays to study the role of HELLS in human osteosarcoma, we observed
      that HELLS has no effect on tumor proliferation and migration. Further, we
      pioneered the study of Hells in developmental tumor models by generating Hells
      conditional knockout osteosarcoma mouse models to examine the role of HELLS in
      osteosarcoma tumor development. We found that loss of Hells in osteosarcoma has
      no effect in tumor initiation and overall survival of mice. This suggests that
      while HELLS may serve as a biomarker for tumorigenesis and for RB-E2F pathway
      status, it is unlikely to serve as a relevant target for therapeutics in
      osteosarcoma.

PMID- 30220968
TI  - Alendronate-induced disruption of actin cytoskeleton and inhibition of
      migration/invasion are associated with cofilin downregulation in PC-3 prostate
      cancer cells.
AB  - Bisphosphonates are used for prevention of osteoporosis and metastatic bone
      diseases. Anti-invasive effects on various cancer cells have also been reported,
      but the mechanisms involved are not well-understood. We investigated the effects
      of the nitrogen-containing bisphosphonate alendronate (ALN) on the regulation of
      actin cytoskeleton in PC-3 cells. We analyzed the ALN effect on the organization
      and the dynamics of actin, and on the cytoskeleton-related regulatory proteins
      cofilin, p21-associated kinase 2 (PAK2), paxillin and focal adhesion kinase.
      Immunostainings of cofilin in ALN-treated PC-3 cells and xenografts were
      performed, and the role of cofilin in ALN-regulated F-actin organization and
      migration/invasion in PC-3 cells was analyzed using cofilin knockdown and
      transfection. We demonstrate that disrupted F-actin organization and decreased
      cell motility in ALN-treated PC-3 cells were associated with decreased levels of
      total and phosphorylated cofilin. PAK2 levels were also lowered but adhesion
      related proteins were not altered. The knockdown of cofilin similarly impaired F
      actin organization and decreased invasion of PC-3 cells, whereas in the cells
      transfected with a cofilin expressing vector, ALN treatment did not decrease
      cellular cofilin levels and migration as in mock transfected cells. ALN also
      reduced immunohistochemical staining of cofilin in PC-3 xenografts. Our results
      suggest that reduction of cofilin has an important role in ALN-induced disruption
      of the actin cytoskeleton and inhibition of the PC-3 cell motility and invasion.
      These data also support the idea that the nitrogen-containing bisphosphonates
      could be efficacious in inhibition of prostate cancer invasion and metastasis, if
      delivered in a pharmacological formulation accessible to the tumors.

PMID- 30220969
TI  - Hematopoietic lineage cell-specific protein 1 (HS1), a hidden player in
      migration, invasion, and tumor formation, is over-expressed in ovarian carcinoma
      cells.
AB  - Hematopoietic lineage cell-specific protein 1 (HS1), which is the hematopoietic
      homolog of cortactin, is an actin-binding protein and Lyn substrate. It is
      upregulated in several cancers and its expression level is associated with
      increased cell migration, metastasis, and poor prognosis. Here we investigated
      the expression and roles of HS1 in ovarian carcinoma cells. We analyzed the
      expression of HS1 in 171 ovarian cancer specimens and determined the association
      between HS1 expression and clinicopathological characteristics, including patient
      outcomes. In patients with stage II-IV disease, positive HS1 expression was
      associated with significantly worse overall survival than negative expression (P
      < 0.05). HS1 was localized in invadopodia in some ovarian cancer cells and was
      required for invadopodia formation. Migration and invasion of ovarian cancer
      cells were suppressed by down-regulation of HS1, but increased in cells that over
      expressed exogenous HS1. Furthermore, ovarian cancer cells that expressed HS1
      shRNA exhibited reduced tumor formation in a mouse xenograft model. Finally, we
      found that tyrosine phosphorylation of HS1 was essential for cell migration and
      invasion. These findings show that HS1 is a useful biomarker for the prognosis of
      patients with ovarian carcinoma and is a critical regulator of cytoskeleton
      remodeling involved in cell migration and invasion.

PMID- 30220970
TI  - Quantitative screening of serum protein biomarkers by reverse phase protein
      arrays.
AB  - Screening biomarkers in serum samples for different diseases has always been of
      great interest because it presents an early, reliable, and, most importantly,
      noninvasive means of diagnosis and prognosis. Reverse phase protein arrays
      (RPPAs) are a high-throughput platform that can measure single or limited sets of
      proteins from thousands of patients' samples in parallel. They have been widely
      used for detection of signaling molecules involved in diseases, especially
      cancers, and related regulation pathways in cell lysates. However, this approach
      has been difficult to adapt to serum samples. Previously, we developed a
      sensitive method called the enhanced protein array to quantitatively measure
      serum protein levels from large numbers of patient samples. Here, we further
      refine the technology on several fronts: 1. simplifying the experimental
      procedure; 2. optimizing multiple parameters to make the assay more robust,
      including the support matrix, signal reporting method, background control, and
      antibody validation; and 3. establishing a method for more accurate
      quantification. Using this technology, we quantitatively measured the expression
      levels of 10 proteins: alpha-fetoprotein (AFP), beta 2 microglobulin (B2M),
      Carcinoma Antigen 15-3(CA15-3), Carcinoembryonic antigen (CEA), golgi protein 73
      (GP73), Growth differentiation factor 15 (GDF15), Human Epididymis Protein 4
      (HE4), Insulin Like Growth Factor Binding Protein 2 (IGFBP2), osteopontin (OPN)
      and Beta-type platelet-derived growth factor receptor (PDGFRB) from serum samples
      of 132 hepatocellular carcinoma (HCC) patients and 78 healthy volunteers. We
      found that 6 protein expression levels are significantly increased in HCC
      patients. Statistical and bioinformatical analysis has revealed decent accuracy
      rates of individual proteins, ranging from 0.617 (B2M) to 0.908 (AFP) as
      diagnostic biomarkers to distinguish HCC from healthy controls. The combination
      of these 6 proteins as a specific HCC signature yielded a higher accuracy of
      0.923 using linear discriminant analysis (LDA), logistic regression (LR), random
      forest (RF) and support vector machine (SVM) predictive model analyses. Our work
      reveals promise for using reverse phase protein arrays for biomarker discovery
      and validation in serum samples.

PMID- 30220972
TI  - The frequency of promoter DNA hypermethylation is decreased in colorectal
      neoplasms of familial adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP) is an inherited disorder characterized by
      numerous colorectal adenomatous polyps with predisposition to the development of
      colorectal cancer (CRC). Here, we conducted genome-wide DNA methylation analysis
      of FAP neoplasms, including seven cancer samples and 16 adenoma samples, using an
      Infinium 450K BeadArray. As controls for sporadic colorectal neoplasms and
      mucosae, we used Infinium 450k data from 297 CRC samples, 45 colorectal adenoma
      samples, and 37 normal mucosa samples with reference to The Cancer Genome Atlas
      and other databases. Unsupervised two-way hierarchical clustering analysis of FAP
      and sporadic CRC/adenoma revealed that CRC was classified into four DNA
      methylation epigenotypes (MEs): high-ME (HME), intermediate-ME (IME), low-ME
      (LME), and normal-like ME (NME). Five FAP neoplasms (two cancer and three
      adenoma) were clustered with IME, whereas 18 FAP neoplasms (five cancer and 13
      adenoma) were clustered into NME. IME FAP neoplasms significantly correlated with
      KRAS mutations, similar to sporadic CRC. Within IME cases, however, aberrant DNA
      methylation was significantly less frequent in FAP neoplasms than sporadic
      neoplasms, and these unmethylated genes included WNT family genes and several
      types of oncogenes. In summary, FAP neoplasms were classified into at least two
      molecular subtypes, i.e., NME in the majority of cases showing mostly no aberrant
      methylation and IME in some cases accompanied by KRAS mutations but less frequent
      aberrant DNA methylation than sporadic neoplasms, suggesting that FAP may follow
      a tumorigenesis pathway different from that of sporadic CRC.

PMID- 30220971
TI  - Mutational analysis of uterine cervical cancer that survived multiple rounds of
      radiotherapy.
AB  - Radiotherapy is an essential component of cancer therapy. Despite advances in
      cancer genomics, the mutation signatures of radioresistant tumors have not yet
      been fully elucidated. To address this issue, we analyzed a unique set of
      clinical specimens from a uterine cervical cancer that repeatedly locally
      recurred after multiple rounds of radiotherapy. Exon sequencing of 409 cancer
      related genes in the treatment-naive tumor and the tumors that recurred after
      initial and secondary radiotherapy identified (i) activating mutations in PIK3CA
      and KRAS, and putative inactivating mutations in SMAD4, as trunk mutation
      signatures that persisted over the clinical course; and (ii) mutations in KMT2A,
      TET1, and NLRP1 as acquired mutation signatures observed only in recurrent tumors
      after radiotherapy. Comprehensive mining of published in vitro genomics data
      pertaining to radiosensitivity revealed that simultaneous mutations in KRAS and
      SMAD4, which have not been described previously in uterine cervical cancer, are
      associated with cancer cell radioresistance. The association between this
      mutation signature and radioresistance was validated by isogenic cell-based
      experiments. These results provide proof-of-principle for the analytical pipeline
      employed in this study, which explores clinically relevant mutation signatures
      for radioresistance, and demonstrate that this approach is worth pursuing with
      larger cohorts in the future.

PMID- 30220973
TI  - Involvement of GLUT1-mediated glucose transport and metabolism in gefitinib
      resistance of non-small-cell lung cancer cells.
AB  - Use of epidermal growth factor receptor (EGFR) inhibitors represented by
      gefitinib and erlotinib has become the standard of treatment for non-small-cell
      lung cancers (NSCLCs) with activating EGFR mutations. However, the majority of
      NSCLCs, which overexpress EGFR without such mutations, are resistant to EGFR
      inhibitors, and the mechanism(s) behind such primary resistance of NSCLCs without
      activating EGFR mutations to EGFR inhibitors still remains poorly understood.
      Here in this study, we show that glucose metabolism mediated by GLUT1, a
      facilitative glucose transporter, is involved in gefitinib resistance of NSCLC
      cells. We found that GLUT1 expression and glucose uptake were increased in
      resistant NSCLC cells after gefitinib treatment and that genetic as well as
      pharmacological inhibition of GLUT1 sensitized not only NSCLC cells with primary
      resistance but also those with acquired resistance to gefitinib. In vivo, the
      combination of systemic gefitinib and a GLUT1 inhibitor, both of which failed to
      inhibit tumor growth when administered alone, significantly inhibited the growth
      of xenograft tumors formed by the implantation of NSCLC cells with wild-type EGFR
      (wt-EGFR). Since our data indicated that GLUT1 was similarly involved in
      erlotinib resistance, our findings suggest that the activity of GLUT1-mediated
      glucose metabolism could be a critical determinant for the sensitivity of NSCLC
      cells to EGFR inhibitors and that concurrent GLUT1 inhibition may therefore be a
      mechanism-based approach to treating NSCLCs resistant to EGFR inhibitors,
      including those with wt-EGFR.

PMID- 30220974
TI  - Absence of correlation between radiation-induced CD8 T-lymphocyte apoptosis and
      sequelae in patients with prostate cancer accidentally overexposed to radiation.
AB  - Purpose: 454 patients with prostate adenocarcinoma were accidentally overexposed
      to radiation in Epinal hospital, France, between August 1999 and January 2007. We
      aimed toevaluate whether radiation-induced CD4 or CD8 T-lymphocyte apoptosis
      (RILA) correlates with the severity of radiation toxicity. Methods: Between 2007
      and 2013, all patients who received more than 108% of the prescribed radiation
      dose, after correction of the treatment plan, were convened, and blood was
      sampled at 6-months follow-up. Maximal Digestive toxicity (MDT) and maximal
      urinary toxicity (MUT) were graded using the Common Terminology Criteria for
      Adverse Events (NCI-CTCAE) v3.0 scale. RILA was assessed using flow cytometry.
      Results: 245 patients were included in our study. After a median follow-up of 4.8
      years, the MDT and MUT reached grade 3-4 in 37 patients and 56 patients,
      respectively. Patients with prostatectomy exhibited a statistically higher grade
      of MUT compared with those treated with definitive radiotherapy (p=0.03). The
      median RILA values were 11.8% and 15.3% for CD4 and CD8 T-lymphocytes,
      respectively. We found no significant correlation between CD4 or CD8 RILA and
      either MDT or MUT. Conclusion: RILA does not correlate with the inter-individual
      variation in MDT or MUT in the largest cohort of patients overexposed to
      radiation. The magnitude of the overdosage probably overrides biological
      predictors of toxicity, including individual radiosensitivity.

PMID- 30220975
TI  - A high-throughput fluorescence polarization assay for discovering inhibitors
      targeting the DNA-binding domain of signal transducer and activator of
      transcription 3 (STAT3).
AB  - Anti-cancer drug discovery efforts to directly inhibit the signal transducer and
      activator of transcription 3 (STAT3) have been active for over a decade following
      the discovery that 70% of cancers exhibit elevated STAT3 activity. The majority
      of research has focused on attenuating STAT3 activity through preventing homo
      dimerization by targeting the SH2 or transcriptional activation domains. Such
      dimerization inhibitors have not yet reached the market. However, an alternative
      strategy focussed on preventing STAT3 DNA-binding through targeting the DNA
      binding domain (DBD) offers new drug design opportunities. Currently, only EMSA
      and ELISA-based methods have been implemented with suitable reliability to
      characterize STAT3 DBD inhibitors. Herein, we present a new orthogonal,
      fluorescence polarization (FP) assay suitable for high-throughput screening of
      molecules. This assay, using a STAT3127-688 construct, was developed and
      optimized to screen molecules that attenuate the STAT3:DNA association with good
      reliability (Z' value > 0.6) and a significant contrast (signal-to-noise ratio >
      15.0) at equilibrium. The assay system was stable over a 48 hour period.
      Significantly, the assay is homogeneous and simple to implement for high
      throughput screening compared to EMSA and ELISA. Overall, this FP assay offers a
      new way to identify and characterize novel molecules that inhibit STAT3:DNA
      association.

PMID- 30220978
TI  - Correction: Mechanosensitive caveolin-1 activation-induced PI3K/Akt/mTOR
      signaling pathway promotes breast cancer motility, invadopodia formation and
      metastasis in vivo.
AB  - [This corrects the article DOI: 10.18632/oncotarget.7583.].

PMID- 30220977
TI  - A patient-derived orthotopic xenograft model enabling human high-grade urothelial
      cell carcinoma of the bladder tumor implantation, growth, angiogenesis, and
      metastasis.
AB  - High-grade urothelial cell carcinoma of the bladder has a poor prognosis when
      lymph nodes are involved. Despite curative therapy for clinically-localized
      disease, over half of the muscle-invasive urothelial cell carcinoma patients will
      develop metastases and die within 5 years. There are currently no described
      xenograft models that consistently mimic urothelial cell carcinoma metastasis. To
      develop a patient-derived orthotopic xenograft model to mimic clinical urothelial
      cell carcinoma progression to metastatic disease, the urothelial cell carcinoma
      cell line UM-UC-3 and two urothelial cell carcinoma patient specimens were doubly
      tagged with Luciferase/RFP and were intra-vesically (IB) instilled into NOD/SCID
      mice with or without lymph node stromal cells (HK cells). Mice were monitored
      weekly with bioluminescence imaging to assess tumor growth and metastasis.
      Primary tumors and organs were harvested for bioluminescence imaging, weight, and
      formalin-fixed for hematoxylin and eosin and immunohistochemistry staining. In
      this patient-derived orthotopic xenograft model, xenograft tumors showed better
      implantation rates than currently reported using other models. Xenograft tumors
      histologically resembled pre-implanted primary specimens from patients,
      presenting muscle-invasive growth patterns. In the presence of HK cells, tumor
      formation, tumor angiogenesis, and distant organ metastasis were significantly
      enhanced in both UM-UC-3 cells and patient-derived specimens. Thus, we
      established a unique, reproducible patient-derived orthotopic xenograft model
      using human high-grade urothelial cell carcinoma cells and lymph node stromal
      cells. It allows for investigating the mechanism involved in tumor formation and
      metastasis, and therefore it is useful for future testing the optimal sequence of
      conventional drugs or the efficacy of novel therapeutic drugs.

PMID- 30220979
TI  - Correction: SEL1L SNP rs12435998, a predictor of glioblastoma survival and
      response to radio-chemotherapy.
AB  - [This corrects the article DOI: 10.18632/oncotarget.3611.].

PMID- 30220976
TI  - Dual targeting of HSP70 does not induce the heat shock response and
      synergistically reduces cell viability in muscle invasive bladder cancer.
AB  - Muscle invasive bladder cancer (MIBC) is a common malignancy and major cause of
      morbidity worldwide. Over the last decade mortality rates for MIBC have not
      decreased as compared to other cancers indicating a need for novel strategies.
      The molecular chaperones HSP70 and HSP90 fold and maintain the 3-dimensional
      structures of numerous client proteins that signal for cancer cell growth and
      survival. Inhibition of HSP70 or HSP90 results in client protein degradation and
      associated oncogenic signaling. Here we targeted HSP70 and HSP90 with small
      molecule inhibitors that trap or block each chaperone in a low client-affinity
      "open" conformation. HSP70 inhibitors, VER155008 (VER) and MAL3-101 (MAL), along
      with HSP90 inhibitor, STA-9090 (STA), were tested alone and in combination for
      their ability to reduce cell viability and alter protein levels in 4 MIBC cell
      lines. When combined, VER+MAL synergistically reduced cell viability in each MIBC
      cell line while not inducing expression of heat shock proteins (HSPs). STA+MAL
      also synergistically reduced cell viability in each cell line but induced
      expression of cytoprotective HSPs indicating the merits of targeting HSP70 with
      VER+MAL. Additionally, we observed that STA induced the expression of the stress
      related transcription factor HSF2 while reducing levels of the co-chaperone TTI1.

PMID- 30220980
TI  - Association of child maltreatment subtypes and long-term physical health in a
      German representative sample.
AB  - Background: Child maltreatment is a major public problem, associated with
      enormous consequences on the individual and socioeconomic level. Studies show a
      clear impact of child maltreatment on long-term physical health. However, there
      is a lack of analyses comprising a wide variety of subtypes of maltreatment and
      addressing cumulative effects of different maltreatment subtypes experienced
      during childhood on physical health. Objective: The objective of this analysis
      was to assess the association of different subtypes and the intensity of child
      maltreatment with long-term physical health outcomes. Methods: In a cross
      sectional observational approach, a representative sample of the German
      population (N=2510) was assessed regarding socioeconomic information, their
      current health status, and their experiences of child maltreatment using the
      Childhood Trauma Questionnaire (CTQ). Chi2-Tests were performed to compare
      differences of physical health conditions in adulthood in association with child
      maltreatment and binary regression analyses to assess the relationship of
      physical health and number of different subtypes of maltreatment experienced
      during childhood. Results: Odds increased significantly for obesity (1.8),
      diabetes (1.26), cancer (1.28), hypertension (1.16), chronic obstructive
      pulmonary disease (1.51), history of myocardial infarction (1.29) and stroke
      (1.31) with increasingenhancing number of experienced subtypes of child
      maltreatment. Growing intensity of each subtype of maltreatment was associated
      with higher rates of all assessed physical health conditions, which could point
      towards a dose-dependency of the relationship between maltreatment and long-term
      physical health. Conclusions: Child maltreatment is associated with increased
      odds for the leading morbidity and mortality causes in Germany. Interventions
      encompassing secondary and primary preventive strategies are critical to target
      this major public health problem and its devastating consequences.

PMID- 30220983
TI  - Response to: Prolonged grief disorder for ICD-11: the primacy of clinical utility
      and international applicability.

PMID- 30220981
TI  - The association between different traumatic life events and suicidality.
AB  - Background: Traumatic life events have been associated with increased risk of
      various psychiatric disorders, even suicidality. Our aim was to investigate the
      association between different traumatic life events and suicidality, by type of
      event and gender. Methods: Women attending a cancer screening programme in
      Iceland (n = 689) and a random sample of men from the general population (n =
      709) were invited to participate. In a web-based questionnaire, life events were
      assessed with the Life Stressor Checklist - Revised, and the Diagnostic and
      Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criterion was used
      to identify traumatic life events. Reports of lifetime suicidal thoughts, self
      harm with suicidal intent and suicide attempt were considered as lifetime
      suicidality. We used Poisson regression, adjusted for demographic factors, to
      express relative risks (RRs) as a measure of the associations between traumatic
      events and suicidality. Results: Response rate was 66% (922/1398). The prevalence
      of lifetime traumatic events was 76% among women and 77% among men. Lifetime
      suicidality was 11% among women and 16% among men. An overall association of
      having experienced traumatic life events with suicidality was observed [RR 2.05,
      95% confidence interval (CI) 1.21-3.75], with a stronger association for men (RR
      3.14, 95% CI 1.25-7.89) than for women (RR 1.45, 95% CI 0.70-2.99). Increased
      likelihood for suicidality was observed among those who had experienced
      interpersonal trauma (RR 2.97, 95% CI 1.67-5.67), childhood trauma (RR 4.09, 95%
      CI 2.27-7.36) and sexual trauma (RR 3.44, 95% CI 1.85-6.37), with a higher
      likelihood for men. In addition, an association between non-interpersonal trauma
      and suicidality was noted among men (RR 3.27, 95% CI 1.30-8.25) but not women (RR
      1.27, 95% CI 0.59-2.70). Conclusion: Findings indicate that traumatic life events
      are associated with suicidality, especially among men, with the strongest
      association for interpersonal trauma.

PMID- 30220982
TI  - A trauma-focused approach for patients with tinnitus: the effectiveness of eye
      movement desensitization and reprocessing - a multicentre pilot trial.
AB  - Background: While normal tinnitus is a short-term sensation of limited duration,
      in 10-15% of the general population it develops into a chronic condition. For 3
      6% it seriously interferes with many aspects of life. Objective: The aim of this
      trial was to assess effectiveness of a trauma-focused approach, eye movement
      desensitization and reprocessing (EMDR), in reducing tinnitus distress. Methods:
      The sample consisted of 35 adults with high levels of chronic tinnitus distress
      from five general hospitals in the Netherlands. Participants served as their own
      controls. After pre-assessment (T1), participants waited for a period of 3
      months, after which they were assessed again (T2) before they received six 90 min
      manualized EMDR treatment sessions in which tinnitus-related traumatic or
      stressful events were the focus of treatment. Standardized self-report measures,
      the Tinnitus Functional Index (TFI), Mini-Tinnitus Questionnaire (Mini-TQ),
      Symptom Checklist-90 (SCL-90) and the Self-Rating Inventory List for Post
      traumatic Stress Disorder (SRIP), were completed again halfway through treatment
      (T3), post-treatment (T4) and at 3 months' follow-up (T5). Results: Repeated
      measures analysis of variance revealed significant improvement after EMDR
      treatment on the primary outcome, TFI. Compared to the waiting-list condition,
      scores significantly decreased in EMDR treatment [t(34) = -4.25, p < .001,
      Cohen's dz  = .72]. Secondary outcomes, Mini-TQ and SCL-90, also decreased
      significantly. The treatment effects remained stable at 3 months' follow-up. No
      adverse events or side effects were noted in this trial. Conclusions: This is the
      first study to suggest that EMDR is effective in reducing tinnitus distress.
      Randomized controlled trials are warranted.

PMID- 30220984
TI  - Prevalence and predictors of posttraumatic stress disorder and depressive
      symptoms among burn survivors two years after the 2015 Formosa Fun Coast Water
      Park explosion in Taiwan.
AB  - Background: Posttraumatic stress disorder (PTSD) and depressive symptoms are
      relatively common in burn survivors. Several previously reported risk factors
      (e.g. burn severity) have not consistently predicted psychological adjustment
      post-burn. Empirically-derived risk factors of PTSD from the meta-analysis and
      theory-derived cognitive variables may be of great predictive value. Objective:
      This study investigated the prevalence of probable DSM-5 PTSD and major
      depression (MDD) and the predictors of PTSD and depressive symptoms in burn
      survivors of the 2015 Formosa Fun Coast Water Park explosion. Three sets of
      predictors were examined: (a) burn-related variables; (b) empirically-derived
      risk factors from the meta-analysis; and (c) theory-derived cognitive variables.
      Method: Participants were 116 burn survivors of the Formosa Fun Coast Water Park
      explosion. The mean age at the disaster was 22.3 +/- 4.2 years; the average total
      body surface area burned (TBSA) was 49.5%. Results: Of our participants, 12.9 and
      20.7% met DSM-5 probable PTSD and MDD two years after the Formosa Fun Coast Water
      Park explosion. No gender differences were observed. For the prediction of PTSD
      symptoms post-burn, theory-derived cognitive variables (adjusted R2 = .562, 95%
      CI [.423, .638]) performed best and provided significantly better prediction than
      empirically-derived risk factors from the meta-analysis (adjusted R2 = .337, 95%
      CI [.180, .412]) and burn-related variables (adjusted R2 = .313, 95% CI [.156,
      .389]). In contrast, the three sets of variables examined provided similar
      predictions for depressive symptoms post-burn (adjusted R2 = .267-.295). Random
      forest regression revealed that theory-derived cognitive variables, particularly
      negative appraisal of symptoms and maladaptive cognitive coping, were considered
      the most important predictors of PTSD symptoms post-burn. Conclusion: The
      prevalence of probable PTSD and MDD were relatively higher in burn survivors.
      Theory-derived cognitive variables substantially improve predictions for PTSD
      symptoms post-burn.

PMID- 30220985
TI  - Testing the ICD-11 proposal for complex PTSD in trauma-exposed adults: factor
      structure and symptom profiles.
AB  - Background: The proposed ICD-11 criteria for trauma-related disorders define
      posttraumatic stress disorder (PTSD) and complex posttraumatic stress disorder
      (cPTSD) as separate disorders. Results of previous studies support the validity
      of this concept. However, due to limitations of existing studies (e.g.
      homogeneity of the samples), the present study aimed to test the construct
      validity and factor structure of cPTSD and its distinction from PTSD using a
      heterogeneous trauma-exposed sample. Method: Confirmatory factor analyses (CFAs)
      were conducted to explore the factor structure of the proposed ICD-11 cPTSD
      diagnosis in a sample of 341 trauma-exposed adults (n = 191 female, M = 37.42
      years, SD = 12.04). In a next step, latent profile analyses (LPAs) were employed
      to evaluate predominant symptom profiles of cPTSD symptoms. Results: The results
      of the CFA showed that a six-factor structure (i.e. symptoms of intrusion,
      avoidance, hyperarousal and symptoms of affective dysregulation, negative self
      concept, and interpersonal problems) fits the data best. According to LPA, a four
      class solution optimally characterizes the data. Class 1 represents moderate PTSD
      and low symptoms in the specific cPTSD clusters (PTSD group, 30.4%). Class 2
      showed low symptom severity in all six clusters (low symptoms group, 24.1%).
      Classes 3 and 4 both exhibited cPTSD symptoms but differed with respect to the
      symptom severity (Class 3: cPTSD, 34.9% and Class 4: severe cPTSD, 10.6%).
      Conclusions: The findings replicate previous studies supporting the proposed
      factor structure of cPTSD in ICD-11. Additionally, the results support the
      validity and usefulness of conceptualizing PTSD and cPTSD as discrete mental
      disorders.

PMID- 30220986
TI  - The Trauma and Life Events (TALE) checklist: development of a tool for improving
      routine screening in people with psychosis.
AB  - Background: Best practice guidelines recommend traumatic events should be
      assessed in psychosis to support the identification and, when indicated,
      treatment of post-traumatic stress reactions. However, routine assessment in
      frontline services is rare, and available tools are not tailored to psychosis.
      Assessment obstacles include lengthy measures, a focus on single, physically
      threatening events, and the exclusion of psychosis-related traumas. Objective: To
      develop and validate a brief trauma screening tool for the identification of
      clinically significant traumas in people with psychosis. Method: The Trauma and
      Life Events (TALE) checklist was developed in conjunction with people with lived
      experience of trauma and psychosis, and specialist clinicians and researchers.
      The psychometric properties (i.e. test-retest reliability, content validity,
      construct validity) of the TALE were evaluated in a sample of 39 people with
      psychosis diagnoses. Results: The TALE displayed moderate psychometric
      acceptability overall, with excellent reliability and convergent validity for
      sexual abuse. High rates of psychosis-related trauma and childhood adversity were
      reported, in particular bullying and emotional neglect. A dose-response
      relationship between cumulative trauma, post-traumatic stress and psychosis was
      found. Conclusions: The TALE is the first screening tool specifically designed to
      meet the needs of routine trauma screening in psychosis services. The
      psychometric limitations highlight the challenge of developing a measure that is
      both sufficiently brief to be useful in clinical settings and comprehensive
      enough to identify all relevant adverse events. Validation of the TALE is now
      required across the spectrum of psychosis.

PMID- 30220987
TI  - Evaluation of aging, diabetes mellitus, and skin wounds by scanning acoustic
      microscopy with protease digestion.
AB  - Scanning acoustic microscopy (SAM) can assess tissue stiffness by calculating the
      speed of sound (SOS) through tissues. SOS increases as tissue stiffness
      increases. Sensitivity to protease digestion depends on protein type,
      concentration, and modification. We analyzed the SOS images of formalin-fixed
      paraffin-embedded skin sections from elderly, young, diabetic, and nondiabetic
      subjects, as well as chronic and acute wounds. SAM provided high-resolution
      histology similar to LM and revealed characteristic SOS alteration following
      pepsin treatment. SOS values of dermis samples from elderly subjects (especially
      females) were lower than those of younger adults, which was indicative of age
      related dermal softening and loosening. SOS values of elderly females were lower
      than those of younger females and elderly males. Dermal SOS showed a positive
      correlation with epidermal thickness. SOS values of epidermis of elderly subjects
      were higher than those of younger adults and showed a rapid decline 0.5h after
      protease digestion. Reticular dermis of diabetic patients exhibited greater
      pepsin resistance than that of nondiabetic patients. Chronic wounds exhibited
      greater SOS values and pepsin resistance than acute wounds. SOS variation with
      aging, diabetes mellitus, and wound fibrosis reflected histological and
      mechanical changes associated with senescence and disease duration. Epidermal
      thickness reflects age-related changes in dermal stiffness.

PMID- 30220989
TI  - Development of a Simplified Ankle Distractor.

PMID- 30220988
TI  - Is the high intensity symptoms experienced by patients admitted with chronic
      obstructive pulmonary disease documented by health professionals? - a prospective
      survey with comparison of patient reported outcomes and medical records.
AB  - Context: Patients with chronic obstructive pulmonary disease (COPD) have a high
      symptom burden and reduced quality of life. There is an increasing attention on
      palliation for patients with COPD. Recognition of symptoms is a prerequisite for
      palliation. Objectives: We aim to investigate the extent to which symptoms in
      patients with COPD are recognized in the documentation of the health
      professionals, indicated in 'Doctors Symptom Recognition Rate' (DSR), 'Nurses
      Symptom Recognition Rate' (NSR) or 'Doctors and/or Nurses Symptom Recognition
      rates '(DNSR) as a team, respectively. Methods: Patients with COPD (n = 40)
      admitted in two respiratory units, responded within 48 h on two symptom-screening
      tools that access quality of life; COPD assessment test (CAT) used for the
      treatment of COPD and EORTC-QLQ-C15-PAL used for palliation in patients with
      cancer. Patient-described symptomatology was compared to the symptoms as
      recognized in the documentation of doctors and/or nurses. Results: There was a
      significant discrepancy between the symptomatology indicated by patients with
      COPD on CAT and EORTC-QLQ-C15-PAL, and the degree by which it was recognized in
      the medical records indicated in DSR or NSR. In 30 out of 44 items DSR or NSR
      were < 70%. There was a significant difference between DNSR versus DSR or NSR,
      respectively, in 19 out of 22 items.Conclusion: A team-based symptom recognition
      DNSR is superior when compared to DSR or NSR. Team-based systematic screening is
      suggested as a pathway to increase symptom recognition in patients with COPD.
      Increased rates of symptom recognition may improve symptom alleviation and thus
      palliation.

PMID- 30220991
TI  - An unusual case of intestinal obstruction due to internal herniation from
      adhesions between two appendices epiploicae.
AB  - Internal hernia of the small bowel is a rare finding especially in previously non
      operated abdomen. Such a hernia occurring due to involvement of appendices
      epiploicae is an even rare instance with less than five reported cases in the
      literature. We encountered a 75-year-old male who had internal herniation of
      small bowel through an aperture created by adhesion between two appendices
      epiploicae in a previously virgin abdomen. Laparotomy and division of adhesion
      was performed to manage him successfully. Even in a virgin abdomen, a high index
      of suspicion along with early intervention is the key to reduction in mortality
      and morbidity in cases intestinal obstruction.

PMID- 30220990
TI  - A behavioral test battery for mouse models of Angelman syndrome: a powerful tool
      for testing drugs and novel Ube3a mutants.
AB  - Background: Angelman syndrome (AS) is a neurodevelopmental disorder caused by
      mutations affecting UBE3A function. AS is characterized by intellectual
      disability, impaired motor coordination, epilepsy, and behavioral abnormalities
      including autism spectrum disorder features. The development of treatments for AS
      heavily relies on the ability to test the efficacy of drugs in mouse models that
      show reliable, and preferably clinically relevant, phenotypes. We previously
      described a number of behavioral paradigms that assess phenotypes in the domains
      of motor performance, repetitive behavior, anxiety, and seizure susceptibility.
      Here, we set out to evaluate the robustness of these phenotypes when tested in a
      standardized test battery. We then used this behavioral test battery to assess
      the efficacy of minocycline and levodopa, which were recently tested in clinical
      trials of AS. Methods: We combined data of eight independent experiments
      involving 111 Ube3a mice and 120 wild-type littermate control mice. Using a meta
      analysis, we determined the statistical power of the subtests and the effect of
      putative confounding factors, such as the effect of sex and of animal weight on
      rotarod performance. We further assessed the robustness of these phenotypes by
      comparing Ube3a mutants in different genetic backgrounds and by comparing the
      behavioral phenotypes of independently derived Ube3a-mutant lines. In addition,
      we investigated if the test battery allowed re-testing the same animals, which
      would allow a within-subject testing design. Results: We find that the test
      battery is robust across different Ube3a-mutant lines, but confirm and extend
      earlier studies that several phenotypes are very sensitive to genetic background.
      We further found that the audiogenic seizure susceptibility phenotype is fully
      reversible upon pharmacological treatment and highly suitable for dose-finding
      studies. In agreement with the clinical trial results, we found that minocycline
      and levodopa treatment of Ube3a mice did not show any sign of improved
      performance in our test battery. Conclusions: Our study provides a useful tool
      for preclinical drug testing to identify treatments for Angelman syndrome. Since
      the phenotypes are observed in several independently derived Ube3a lines, the
      test battery can also be employed to investigate the effect of specific Ube3a
      mutations on these phenotypes.

PMID- 30210784
TI  - Insulin resistance indices and coronary risk in adults from Maracaibo city,
      Venezuela: A cross sectional study.
AB  - Background: Insulin resistance (IR) is a metabolic disorder related to
      atherosclerosis. Its measurement is of great importance not only as a marker of
      diabetes but also for cardiovascular disease. The aim of this research study was
      to evaluate the relationship between various IR indices and coronary risk in an
      adult population from Maracaibo city, Venezuela. Methods: The Maracaibo City
      Metabolic Syndrome Prevalence Study is a descriptive, cross-sectional study with
      random and multi-stage sampling. In this sub study, 1272 individuals of both
      genders were selected with the measurement of basal insulin and coronary risk
      according to the Framingham-Wilson formula calibrated for our population. The
      insulin resistance indices evaluated were HOMA2-IR, triglycerides and glucose
      index (TyG) and triglycerides/HDL ratio (TG/HDL). The predictive capacity and
      association between each index and the coronary risk event in 10 years were
      determined. Results: Of the evaluated population, 55.2% were female, 34.8% had a
      coronary risk >=5% in 10 years, with the TG/HDL and TyG indices showing the
      highest AUC 0.712 (0.681-0.743) and 0.707 (0.675-0.739), respectively; compared
      to HOMA2-IR. Both were also the indices most associated with increased coronary
      risk, especially TG/HDL >=3 with a higher association [OR = 2.83 (1.74-4.61);
      p<0.01] after multivariable adjustment. Conclusions: TyG (>=4.5) and TG/HDL (>=3)
      indices showed a great predictive capacity of higher coronary risk, with being
      TG/HDL more associated even after adjusting for abdominal obesity and hs-CRP.
      Therefore, these represent useful tools for determining IR.

PMID- 30220992
TI  - Attracting Common Carp to a bait site with food reveals strong positive
      relationships between fish density, feeding activity, environmental DNA, and sex
      pheromone release that could be used in invasive fish management.
AB  - Measurement of environmental DNA (eDNA) is becoming a common technique to survey
      for rare and invasive fish due to its sensitivity and specificity. However, its
      utility is limited by an incomplete understanding of factors governing its
      sources and fates. Failure to detect eDNA is especially difficult to interpret so
      surveillance techniques often collect large numbers of samples across broad
      regions. If, however, fish could be reliably attracted to a single location where
      their eDNA could be easily measured that would be useful. We conducted a proof-of
      concept study of this idea using invasive Common Carp. We monitored the
      distribution of radio-tagged Carp and their eDNA across a 67 ha lake focusing at
      the bait site while a pheromone (Prostaglandin F2alpha; PGF 2alpha) was also
      measured to determine their reproductive condition. Prior to baiting, Carp were
      patchily distributed and while eDNA was occasionally detectable, it was patchy
      and only loosely associated with moderately dense groups of fish. Further,
      neither Carp, nor their eDNA were consistently measurable at the bait site and
      surrounding region, and the pheromone was not measurable at all. However, once
      baiting commenced, Carp started visiting the bait site and feeding, especially at
      night, where eDNA levels increased 500-fold as fish densities doubled and PGF
      2alpha became detectable. Fish presence, eDNA and pheromone concentrations peaked
      at night after 6 days, strongly suggesting feeding activity was the main driver.
      While the presence of eDNA precisely coincided with this aggregation, levels had
      dropped dramatically within 5 m. PGF 2alpha levels dropped less rapidly and
      demonstrated the presence of live mature fish. We suggest that food could be used
      to train fish to come to locations where they otherwise are too scarce to be
      reliably measured, increasing their eDNA release, making them measurable, and
      their reproductive condition also discernable by measuring pheromones.

PMID- 30210785
TI  - Factors influencing the higher incidence of tuberculosis among migrants and
      ethnic minorities in the UK.
AB  - Migrants and ethnic minorities in the UK have higher rates of tuberculosis (TB)
      compared with the general population. Historically, much of the disparity in
      incidence between UK-born and migrant populations has been attributed to
      differential pathogen exposure, due to migration from high-incidence regions and
      the transnational connections maintained with TB endemic countries of birth or
      ethnic origin. However, focusing solely on exposure fails to address the
      relatively high rates of progression to active disease observed in some
      populations of latently infected individuals. A range of factors that
      disproportionately affect migrants and ethnic minorities, including genetic
      susceptibility, vitamin D deficiency and co-morbidities such as diabetes mellitus
      and HIV, also increase vulnerability to infection with Mycobacterium tuberculosis
      (M.tb) or reactivation of latent infection. Furthermore, ethnic socio-economic
      disparities and the experience of migration itself may contribute to differences
      in TB incidence, as well as cultural and structural barriers to accessing
      healthcare. In this review, we discuss both biological and anthropological
      influences relating to risk of pathogen exposure, vulnerability to infection or
      development of active disease, and access to treatment for migrant and ethnic
      minorities in the UK.

PMID- 30210788
TI  - Preliminary study on the inhibitory effect of seaweed Gracilaria verrucosa
      extract on biofilm formation of Candida albicans cultured from the saliva of a
      smoker.
AB  - Background:Candida albicans is an opportunistic fungus that might infect the oral
      cavity. Increased colony numbers of C. albicans in the mouth can be caused by
      multiple factors, such as smoking, weakened immune system, antibiotics use and
      immune-compromised condition. Smoking can increase expression of virulence
      factors of C. albicans and make it stronger. One virulence factor of C. albicans
      is biofilm formation. The ability of creating biofilm makes C. albicans more
      tolerant to commercial antifungal agents. The objective of this preliminary study
      was to examine the ability of the seaweed G.verrucosa extracts to inhibit the
      formation of biofilm by C. albicans isolated from the saliva of a smoker.
      Methods: The extract of G. verrucosa was prepared by maceration using 96%
      methanol and subjected for phytochemical analysis. C. albicans was isolated from
      the saliva of a smoker who voluntarily participated in the study after providing
      informed consent. In triplicate, the fungus was cultured in the growth medium
      containing increased concentrations of G. verrucosa (6.25, 12.5, 25, 50, 75 and
      100% ).The same reaction using fluconazole 0.31 ug/ml C. albicans was prepared as
      positive control. Biofilm formation was accessed based on optical density of cell
      mixtures using an ELISA reader. The data obtained were subjected to Kruskal
      Wallis test at a significance limit of 0.05. Results: Methanol extract of seaweed
      G. verrucosa contained three bio-active compounds namely steroids, terpenoid, and
      tannins. Inhibitory activity of seaweed extracts on C. albicans biofilm formation
      increased as their concentration increased. The highest inhibitory effect was
      recorded at fungus culture treated with seaweed concentration of 25% at 24 hours
      of time exposure. Conclusions: Seaweed G. verrucosa extract contained steroids,
      terpenoids and tannins that were able to effectively inhibit the formation of
      biofilm by C. albicans at the concentration of 25% after 24 hours of time
      exposure.

PMID- 30210789
TI  - Acute hip fracture surgery anaesthetic technique and 30-day mortality in Sweden
      2016 and 2017: A retrospective register study.
AB  - Background: Hip fractures affect 1.6 million patients yearly worldwide, often
      elderly with complex comorbidity. Mortality following surgery for acute hip
      fracture is high and multifactorial; high age, comorbidities and
      complication/deterioration in health following surgery. Whether the anaesthesia
      technique affects the 30-day mortality rate has been studied widely without
      reaching a consensus. The primary aim of this study was to determine anaesthetic
      techniques used in Sweden and their impact on the 30-day mortality rate in
      elderly undergoing acute hip fracture surgery. Other aims were to study the
      impact of age, gender, ASA class, fracture type and delay in surgery on the 30
      day mortality rate. Methods: Data from 13,649 patients >=50 years old who had
      undergone acute hip fracture surgery and been reported to Swedish perioperative
      register (SPOR) between 2016 and 2017 were analysed.     Results: The most
      commonly used anaesthetic technique was neuraxial anaesthesia (NA; 11,257, 82%),
      followed by general anaesthesia (GA; 2,190, 16%) and combined general and
      neuraxial anaesthesia (CA; 202, 1.5%) out of the 13,649 studied. The 30-day
      mortality rate was 7.7% for the entire cohort; GA 7.8%, NA 7.7% and CA 7.4%.
      Mortality was higher in elderly patients, those with a high ASA class,
      pertrochanteric fracture and males.     Conclusions: The present study showed
      that NA is by far the most common anaesthetic technique for acute hip fracture
      surgery in Sweden. However, the anaesthetic technique used during this type of
      surgery had no impact on the 30-day mortality rate in patients. Increasing age,
      ASA class and male gender increased the 30-day mortality.

PMID- 30220997
TI  - Carbon Dot Incorporated Multi-walled Carbon Nanotube Coated Filters for Bacterial
      Removal and Inactivation.
AB  - Multi-walled carbon nanotube (MWCNT) filters incorporated with carbon quantum
      dots (CDots) or single-walled carbon nanotubes (SWCNTs) were produced for
      bacteria removal from aqueous solutions and also for inactivating the captured
      bacteria. TMTP Millipore membranes were used as the base of these filters. The
      results showed that filters with higher MWCNT loading had higher bacterial
      removal efficiencies. Filters with a MWCNT loading of 4.5 mg were highly
      effective at removing bacteria from aqueous solution, resulting in a log
      reduction of 6.41, 6.41, and 5.41 of E. coli cell numbers in filtrates compared
      to MWCNT filters without coating, MWCNTs filters with 0.15mg CDot coating, and
      MWCNTs filters with 0.15mg SWCNT coating, respectively. Ionic strength played an
      important role in bacteria removal. A higher NaCl concentration resulted in
      higher bacteria removal efficiencies of the filters. Both CDot coatings and SWCNT
      coatings did not significantly affect the MWCNT filter effects (P > 0.05). The
      coatings, especially CDot coatings, significantly inhibited the activities of
      bacteria retained on the filter surfaces (P < 0.05). The inhibitory rates were
      94.21% or 73.17% on the MWCNT filter surfaces coated with 0.2 mg CDots or SWCNTs,
      respectively. These results demonstrated that MWCNT filters with CDot coatings
      were highly effective to remove bacteria from water and to inhibit the activities
      of the captured bacteria on filter surfaces.

PMID- 30220998
TI  - Organ preservation with targeted rapamycin nanoparticles: a pre-treatment
      strategy preventing chronic rejection in vivo.
AB  - Hypothermic preservation is the standard of care for storing organs prior to
      transplantation. Endothelial and epithelial injury associated with hypothermic
      storage causes downstream graft injury and, as such, the choice of an ideal donor
      organ preservation solution remains controversial. Cold storage solutions, by
      design, minimize cellular necrosis and optimize cellular osmotic potential, but
      do little to assuage immunological cell activation or immune cell priming post
      transplantation. Thus, here we explore the efficacy of our previously described
      novel Targeted Rapamycin Micelles (TRaM) as an additive to standard-of-care
      University of Wisconsin preservation solution as a means to alter the
      immunological microenvironment post transplantation using in vivo models of
      tracheal and aortic allograft transplantation. In all models of transplantation,
      grafts pre-treated with 100 ng mL-1 of TRaM augmented preservation solution ex
      vivo showed a significant inhibition of chronic rejection post-transplantation,
      as compared to UW augmented with free rapamycin at a ten-fold higher dose. Here,
      for the first time, we present a novel method of organ pretreatment using a
      nanotherapeutic-based cellular targeted delivery system that enables donor
      administration of rapamycin, at a ten-fold decreased dose during cold storage.
      Clinically, these pretreatment strategies may positively impact post-transplant
      outcomes and can be readily translated to clinical scenarios.

PMID- 30220999
TI  - Predictive factors for multidrug-resistant gram-negative bacteria among
      hospitalised patients with complicated urinary tract infections.
AB  - Background: Patients with complicated urinary tract infections (cUTIs) frequently
      receive broad-spectrum antibiotics. We aimed to determine the prevalence and
      predictive factors of multidrug-resistant gram-negative bacteria in patients with
      cUTI. Methods: This is a multicenter, retrospective cohort study in south and
      eastern Europe, Turkey and Israel including consecutive patients with cUTIs
      hospitalised between January 2013 and December 2014. Multidrug-resistance was
      defined as non-susceptibility to at least one agent in three or more
      antimicrobial categories. A mixed-effects logistic regression model was used to
      determine predictive factors of multidrug-resistant gram-negative bacteria cUTI.
      Results: From 948 patients and 1074 microbiological isolates, Escherichia coli
      was the most frequent microorganism (559/1074), showing a 14.5% multidrug
      resistance rate. Klebsiella pneumoniae was second (168/1074) and exhibited the
      highest multidrug-resistance rate (54.2%), followed by Pseudomonas aeruginosa
      (97/1074) with a 38.1% multidrug-resistance rate. Predictors of multidrug
      resistant gram-negative bacteria were male gender (odds ratio [OR], 1.66; 95%
      confidence interval [CI], 1.20-2.29), acquisition of cUTI in a medical care
      facility (OR, 2.59; 95%CI, 1.80-3.71), presence of indwelling urinary catheter
      (OR, 1.44; 95%CI, 0.99-2.10), having had urinary tract infection within the
      previous year (OR, 1.89; 95%CI, 1.28-2.79) and antibiotic treatment within the
      previous 30 days (OR, 1.68; 95%CI, 1.13-2.50). Conclusions: The current high rate
      of multidrug-resistant gram-negative bacteria infections among hospitalised
      patients with cUTIs in the studied area is alarming. Our predictive model could
      be useful to avoid inappropriate antibiotic treatment and implement antibiotic
      stewardship policies that enhance the use of carbapenem-sparing regimens in
      patients at low risk of multidrug-resistance.

PMID- 30221001
TI  - Civil servants' demand for social health insurance in Northwest Ethiopia.
AB  - Background: Absence of reliable health insurance schemes is a key challenge to
      meet the universal health coverage target of the Sustainable Development Goals
      (SDGs). Ethiopian health system is characterized by under financing, low
      protection mechanisms for the poor, and lack of mechanisms of risk pooling and
      cost sharing. Ethiopia is implementing social health insurance (SHI) scheme to
      reduce out of pocket payment (OOP) and improve access and use of healthcare. This
      study aimed to determine the demand for SHI among civil servants and associated
      factors in Northwest Ethiopia. Methods: An institution-based cross-sectional
      study was conducted in Bahir Dar city from 557 randomly selected civil servants
      using structured and self-administered questionaire. The questionnaire included
      questions measuring demand for SHI and demographic, socio-economic, healthcare
      related and personal and behavioral factors. Data were first entered in Epi-Info
      version 7.0 and transferred to SPSS version 20 for analysis. Descriptive
      statistics, bivariate and multivariable logistic regression analysis were
      performed. Results: From the total calculated sample size of 557, 488 respondents
      returned the questionnaire giving a response rate of 88%. Nearly three-fourth of
      the respondents, 355 (72.7%), reported their need to be enrolled in a SHI scheme.
      Two-third of the respondents 325 (66.6%) were willing to pay for their
      enrollment. Overall, three hundred and two (61.9%) were demanding SHI. Having
      good awareness about health insurance [AOR = 4.39, 95% CI = (1.82-12.89)] and
      trust on a health insurance agency [AOR = 3.0, 95% CI = (1.57-5.72)], were
      significantly associated with the demand for SHI among civil servants.
      Conclusion: The demand for SHI among civil servants were higher. The awareness
      towards SHI and trust on the SHI agency were significantly associated with demand
      for SHI. As Ethiopia aspires to insure all employees of the formal sector, and
      improving the awareness of civil servants about SHI and the agency providing the
      service could improve demand for SHI. Further research is important on healthcare
      organizational and professional readiness to handle the upcoming insurance driven
      quality health service need and health seeking behavioral change.

PMID- 30221000
TI  - Genetic assessment of inbred chicken lines indicates genomic signatures of
      resistance to Marek's disease.
AB  - Background: Marek's disease (MD) is a highly contagious pathogenic and oncogenic
      disease primarily affecting chickens. However, the mechanisms of genetic
      resistance for MD are complex and not fully understood. MD-resistant line 63 and
      MD-susceptible line 72 are two highly inbred progenitor lines of White Leghorn.
      Recombinant Congenic Strains (RCS) were developed from these two lines, which
      show varied susceptibility to MD. Results: We investigated genetic structure and
      genomic signatures across the genome, including the line 63 and line 72, six
      RCSs, and two reciprocally crossed flocks between the lines 63 and 72 (F1 63 * 72
      and F1 72 * 63) using Affymetrix(r) Axiom(r) HD 600 K genotyping array. We
      observed 18 chickens from RCS lines were specifically clustered into resistance
      sub-groups distributed around line 63. Additionally, homozygosity analysis was
      employed to explore potential genetic components related to MD resistance, while
      runs of homozygosity (ROH) are regions of the genome where the identical
      haplotypes are inherited from each parent. We found several genes including SIK,
      SOX1, LIG4, SIK1 and TNFSF13B were contained in ROH region identified in
      resistant group (line 63 and RCS), and these genes have been reported that are
      contribute to immunology and survival. Based on FST based population differential
      analysis, we also identified important genes related to cell death and anti
      apoptosis, including AKT1, API5, CDH13, CFDP and USP15, which could be involved
      in divergent selection during inbreeding process. Conclusions: Our findings offer
      valuable insights for understanding the genetic mechanism of resistance to MD and
      the identified genes could be considered as candidate biomarkers in further
      evaluation.

PMID- 30221002
TI  - Emotional eating and weight regulation: a qualitative study of compensatory
      behaviors and concerns.
AB  - Background: Emotional eating, or overeating in response to negative emotions, is
      a behavior endorsed by both normal weight and people with overweight/obesity. For
      some individuals, emotional eating contributes to weight gain and difficulties
      losing weight. However, there are also many who engage in emotional eating who
      maintain a normal weight. Little is known about the mechanisms by which these
      individuals are able to regulate their weight. Methods: The present study seeks
      to gain insight into the behaviors of individuals of normal weight who engage in
      emotional eating through a series of one-on-one, 1-h long, qualitative
      interviews. Interviews were semi-structured and guided by questions pertaining to
      participants' compensatory behaviors used to regulate weight and concerns
      regarding their emotional eating. All interviews were transcribed and then
      objected to a thematic analysis of their content. Results: The results of this
      analysis showed that participants endorsed using physical activity, controlling
      their eating behaviors, and engaging in alternative stress reduction and coping
      strategies to mitigate the effects of their emotional eating. They reported
      concern over the effects of emotional eating on their weight, body image, and
      health and saw this behavior as an unhealthy coping mechanism that was difficult
      to control. Conclusions: These results suggest that programs promoting exercise,
      mindful eating, emotion regulation, and positive body image could have a positive
      effect on emotional eaters who struggle to maintain a healthy weight.

PMID- 30221003
TI  - Inhibition of return for body images in individuals with shape/weight based self
      worth.
AB  - Background: Attentional biases for body shape and weight information have been
      found in people with eating disorders, indicating disorder-specific changes in
      the way this information is processed. To date, the literature has focused on the
      initial capture of attention, with little research on the maintenance of
      attention to shape/weight-related information. The current study aims to
      investigate the occurrence of attentional maintenance through the use of an
      Inhibition of Return task to shape and weight stimuli in those with and without
      an eating disorder. Method: Three groups of female participants between the ages
      of 16-30 years undertook an Inhibition of Return task with target images of
      female bodies and control images of animals. The groups were an eating disorder
      group (n = 20), a High shape/weight based self-worth group (n = 23), and a Low
      shape/weight based self-worth group (n = 26). Results: The results indicated
      differential patterns of Inhibition of Return between the High and Low
      shape/weight based self-worth groups. The High group displayed increased
      inhibition of return for the shape/weight stimuli relative to control stimuli,
      while the Low group displayed reduced inhibition of return for the shape/weight
      stimuli compared to control stimuli. The ED group displayed a similar pattern of
      results to the High group, but this did not reach significance. Conclusion: The
      current findings indicate that young women without an eating disorder who base
      their self-worth on shape/weight display a pattern of avoidance of shape/weight
      stimuli that is in direct contrast to those at low risk of developing eating
      disorders. The possible implications of these specific patterns of inhibition of
      return across those at varying levels of risk for an eating disorder are
      discussed along with their implications for intervention approaches.

PMID- 30221005
TI  - Cefepime dosing regimens in critically ill patients receiving continuous renal
      replacement therapy: a Monte Carlo simulation study.
AB  - Background: Cefepime can be removed by continuous renal replacement therapy
      (CRRT) due to its pharmacokinetics. The purpose of this study is to define the
      optimal cefepime dosing regimens for critically ill patients receiving CRRT using
      Monte Carlo simulations (MCS). Methods: The CRRT models of cefepime disposition
      during 48 h with different effluent rates were developed using published
      pharmacokinetic parameters, patient demographic data, and CRRT settings.
      Pharmacodynamic target was the cumulative percentage of a 48-h period of at least
      70% that free cefepime concentration exceeds the four times susceptible
      breakpoint of Pseudomonas aeruginosa (minimum inhibitory concentration, MIC of
      8). All recommended dosing regimens from available clinical resources were
      evaluated for the probability of target attainment (PTA) using MCS to generate
      drug disposition in a group of 5000 virtual patients for each dose. The optimal
      doses were defined as achieving the PTA at least 90% of virtual patients with
      lowest daily doses and the acceptable risk of neurotoxicity. Results: Optimal
      cefepime doses in critically ill patients receiving CRRT with Kidney Disease:
      Improving Global Outcomes (KDIGO) recommended effluent rates were a regimen of 2
      g loading dose followed by 1.5-1.75 g every 8 h for Gram-negative infections with
      a neurotoxicity risk of < 17%. Cefepime dosing regimens from this study were
      considerably higher than the recommended doses from clinical resources.
      Conclusion: All recommended dosing regimens for patients receiving CRRT from
      available clinical resources failed to achieve the PTA target. The optimal dosing
      regimens were suggested based on CRRT modalities, MIC values, and different
      effluent rates. Clinical validation is warranted.

PMID- 30221004
TI  - Time-lapse live cell imaging to monitor doxorubicin release from DNA origami
      nanostructures.
AB  - Self-assembled DNA nanostructures have attracted significant research interest in
      biomedical applications because of their excellent programmability and
      biocompatibility. To develop multifunctional drug delivery from DNA
      nanostructures, considerable key information is still needed for clinical
      application. Traditional fixed endpoint assays do not reflect the dynamic and
      heterogeneous responses of cells with regard to drugs, and may lead to the
      misinterpretation of experimental results. For the first time, an integrated time
      lapse live cell imaging system was used to study the cellular internalization and
      controlled drug release profile of three different shaped DNA origami/doxorubicin
      (DOX) complexes for three days. Our results demonstrated the dependence of DNA
      nanostructures on shape for drug delivery efficiency, while the rigid 3D DNA
      origami triangle frame exhibited enhanced cellular uptake capability, as compared
      with flexible 2D DNA structures. In addition, the translocation of released DOX
      into the nucleus was proved by fluorescence microscopy, in which a DOX-loaded 3D
      DNA triangle frame displayed a stronger accumulation of DOX in nuclei. Moreover,
      given the facile drug loading and auto fluorescence of the anti-cancer drug, DOX,
      our results suggest that the DNA nanostructure is a promising candidate, as a
      label-free nanocarrier, for DOX delivery, with great potential for anticancer
      therapy as well.

PMID- 30221006
TI  - Pharmacokinetics of metformin in patients with chronic kidney disease stage 4 and
      metformin-naive type 2 diabetes.
AB  - The pharmacokinetics of metformin therapy in patients with chronic kidney disease
      stage 4 (CKD-4) were studied using data from the largest Phase I consecutive
      cohort trial yet performed in this population. Eighteen metformin-naive men and
      women with Type 2 Diabetes and creatinine clearance (CrCl) in the range 18-49
      mL/min (eGFR 15-29 mL/min/1.73 m2) were allocated to daily immediate-release
      metformin of 250 mg, 500 mg, or 1000 mg. A first-dose profile and trough
      concentrations for 4 weeks were taken on all patients. Pharmacokinetic (PK)
      parameters were estimated by fitting a first-order compartment model with
      absorption in a peripheral compartment to concentrations measured 24 hours post
      first dose. Single-dose PK parameters time to maximum concentration (tmax) and
      maximum concentration (Cmax) were consistent with previous observations in
      patients with normal renal function (healthy and diabetic), as was the
      association between CrCl and apparent total oral clearance (Cl/F). However,
      patients with a CrCl below 32 mL/min had trough concentrations that were
      consistently above the steady-state minimum implied by the population PK model.
      This suggests the model may not apply to patients with CrCl below 32 mL/min.
      Metformin in doses of 500-1000 mg/day could be taken by CKD-4 patients. However,
      the single-compartment model breaks down as CrCl declines below 32 mL/min
      suggesting that metformin levels should be monitored regularly in progressive
      stage 4 CKD.

PMID- 30221007
TI  - Direct activation of relatively unstrained carbon-carbon bonds in homogeneous
      systems.
AB  - New modes of chemical reactivity are of high value to synthetic organic
      chemistry. In this vein, carbon-carbon (C-C) activation is an emerging field that
      offers new possibilities for synthesizing valuable complex molecules. This review
      discusses the pioneering stoichiometric discoveries in this field up to the most
      recent synthetic applications that apply catalytic transformations. Specifically,
      the review focuses on C-C activation in relatively unstrained systems, including
      stoichiometric reactions, chelation-directed and chelation-free catalytic
      reactions. While the field of C-C activation of relatively unstrained systems is
      underdeveloped, we expect that this review will provide insight into new
      developments and pave the path for robust, practical applications.

PMID- 30221008
TI  - Racial Differences in the Effect of Marriageable Males on Female Family Headship.
AB  - Female family headship has strong implications for endemic poverty in the United
      States. Consequently, it is imperative to explore the chief factors that
      contribute to this problem. Departing from prior literature that places
      significant weight on welfare-incentive effects, our study highlights the role of
      male marriageability in explaining the prevalence of never-married female family
      headship for blacks and whites. Specifically, we examine racial differences in
      the effect of male marriageability on never-married female headship from 1980 to
      2010. By exploiting data from IPUMS-USA (N = 4,958,722) and exogenous variation
      from state-level sentencing reforms, the study finds that the decline in the
      relative supply of marriageable males significantly increases the incidence of
      never-married female family headship for blacks but not for whites.

PMID- 30221010
TI  - Improving Edge Crystal Identification in Flood Histograms Using Triangular Shape
      Crystals.
AB  - This work presents a method to improve the separation of edge crystals in PET
      block detectors. As an alternative to square-shaped crystal arrays, we used an
      array of triangular-shaped crystals. This increases the distance between the
      crystal centres at the detector edges potentially improving the separation of
      edge crystals. To test this design, we have compared the flood histograms of two
      4*4 scintillator arrays in both square and triangular configurations. The quality
      of the flood histogram was quantified using the fraction of events positioned in
      the correct crystal based on a 2D Gaussian fit of the segmented flood histograms.
      In the first study, the two crystal arrays were coupled with the SiPM directly
      using optical grease, and the flood histogram quality for the edge and corner
      crystals in the triangular-shaped array were much better than that for those
      crystals in the square-shaped array. The average light collection efficiency for
      the triangular-shaped array was 5.9% higher than that for the square-shaped
      array. The average energy resolution for the triangular and square shape array
      were 11.6% and 13.2% respectively. In the second study, two light guides with
      thickness 1 mm and 2 mm were used between the crystal arrays and the SiPM. The
      thicker lightguide degraded the light collection efficiency and energy resolution
      due to the light loss introduced by the light guide. However, in the 2-mm thick
      lightguide case, the flood histogram quality for the edge and corner crystals in
      the square-shaped array were improved due to better separation of those crystals
      in the flood histogram. Comparing the performance of the two crystal arrays with
      three different light guides, the triangular-shaped crystal array with no
      lightguide gave the best performance.

PMID- 30221009
TI  - Current challenges in the diagnosis of zearalenone toxicosis as illustrated by a
      field case of hyperestrogenism in suckling piglets.
AB  - Background: The mycotoxin zearalenone (ZEN) causes functional and morphological
      alterations in reproductive organs of pigs. In the field, diagnosis of ZEN
      induced disorders is often challenging, as relevant feed lots are no longer
      available, or feed analysis results are not conclusive. Here, we report a field
      case of hyperestrogenism in newborn piglets. Surprisingly, more than 50 fungal
      metabolites were detected in hay pellets fed to gestating sows, including ZEN and
      its modified form zearalenone-14-sulfate (ZEN-14-S). Despite the broad
      contamination range in this unconventional feed component, a definite diagnosis
      of mycotoxicosis could not be achieved. In this context, current limitations
      regarding the confirmation of suspected cases of ZEN-induced disorders are
      discussed, covering both feed analysis and the biomarker approach. Case
      presentation: A piglet producer with 200 sows experienced a sudden increase in
      suckling piglet losses up to 30% by lower vitality and crushing. Predominant
      clinical signs were splay legs and signs of hyperestrogenism such as swollen and
      reddened vulvae in newborn piglets. The first differential diagnosis was ZEN
      mycotoxicosis although feed batches had not been changed for months with the
      exception of ground hay pellets, which had been included in the diet five months
      before. Analysis of hay pellets resulted in a sum value of ZEN and its modified
      forms of more than 1000 MUg/kg, with ZEN-14-S alone accounting for 530 MUg/kg.
      Considering the inclusion rate of 7% in the diet for gestating sows, the severe
      impact of the additional ZEN load due to the contaminated hay pellets seemed
      unrealistic but could not be completely excluded either. One month after hay
      pellets had been removed from the diet no further clinical signs were observed.
      Conclusions: Enrichment materials and other fibre sources can contain significant
      amounts of mycotoxins and should be therefore included in feed analysis. Adequate
      methods for broad spectrum mycotoxin determination, including modified
      mycotoxins, are important. As highlighted by this field case, there is a need to
      establish reliable biomarkers for ZEN exposure in pigs. Currently, available
      biomarkers do not allow a solid prediction of the ZEN intake of pigs under field
      conditions, which limits their application to experimental studies.

PMID- 30221011
TI  - Randomized study of doxorubicin-based chemotherapy regimens, with and without
      sildenafil, with analysis of intermediate cardiac markers.
AB  - Background: Doxorubicin chemotherapy is used across a range of adult and
      pediatric malignancies. Cardiac toxicity is common, and dysfunction develops over
      time in many patients. Biomarkers used for predicting late cardiac dysfunction
      following doxorubicin exposure have shown promise. Preclinical studies have
      demonstrated potential cardioprotective effects of sildenafil. Methods: We sought
      to confirm the safety of adding sildenafil to doxorubicin-based chemotherapy and
      assess N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) and high sensitivity
      cardiac troponin I (hsTnI) as early markers of anthracycline-induced
      cardiotoxicity. We randomized 27 patients (ages 31-77, 92.3% female) receiving
      doxorubicin chemotherapy using a blocked randomization scheme with randomly
      permuted block sizes to receive standard chemotherapy alone or with the addition
      of sildenafil. The study was not blinded. Sildenafil was dosed at 100 mg by mouth
      daily during therapy; patients took sildenafil three times daily on the day of
      doxorubicin. Doxorubicin dosing and schedule were dependent on the treatment
      regimen. Echocardiography was obtained prior to initiation of treatment and
      routinely thereafter up to 4 years. NT-proBNP and hsTnI were obtained with each
      cycle before, 1-3 h after, and 24 h after doxorubicin. Results: Fourteen patients
      were randomized to receive standard doxorubicin chemotherapy alone (14 treated
      and analyzed), while 13 patients were randomized to the experimental doxorubicin
      and sildenafil arm (10 treated and analyzed). No toxicity signal was seen with
      the addition of sildenafil to doxorubicin-based regimens. There was no
      statistical difference between the treatment arms in relation to the change of
      mean left ventricular ejection fraction (LVEF) between the first and last
      evaluation. In both arms, hsTnI levels increased over time; however, elevated
      hsTnI was not associated with declines in LVEF. Conclusion: Adding sildenafil was
      safe, but did not offer cardioprotection following doxorubicin treatment.
      Increases in hsTnI levels were observed over time, but elevations during therapy
      did not correlate with subsequent decreases in LVEF. Trial registration: This
      clinical trial (NCT01375699) was registered at www.clinicaltrials.gov on June 17,
      2011.

PMID- 30221012
TI  - Hemostasis, bleeding and thrombosis in liver disease.
AB  - The presence of cirrhosis poses an increased risk of both thrombosis and bleeding
      in individuals with chronic liver disease. This duality is a result of a dynamic
      disequilibrium between procoagulant and anticoagulant states in individuals with
      cirrhosis. The mechanism of this imbalance in cirrhosis remains unclear. It is
      known that the progression of cirrhosis leads to decreased synthetic function and
      a concurrent lack of natural anticoagulants. Other proposed mechanisms
      contributing to this hemostatic imbalance include decreased platelet production,
      increased platelet destruction from hypersplenism, decreased synthesis of Vitamin
      K-dependent and independent clotting factors and anticoagulant factors, and
      alterations in purinergic signaling pathways. Given the current state of flux in
      our understanding of bleeding and thrombophilia in cirrhosis, the recommendations
      for treatment of these conditions are still evolving. We provide a current update
      on the proposed pathophysiology of altered hemostasis and thrombophilia in
      cirrhosis. We discuss recent studies in portal vein thrombosis (PVT) and venous
      thromboembolism (VTE), which are the common thrombotic consequences of cirrhosis,
      resulting in substantive morbidity and mortality. To address these, we discuss
      new prophylactic interventions and current treatment options to manage the
      heightened risk of thrombosis in cirrhosis, while limiting hemorrhagic
      complications.

PMID- 30221013
TI  - gamma-tubulin as a signal-transducing molecule and meshwork with therapeutic
      potential.
AB  - Knowledge of gamma-tubulin is increasing with regard to the cellular functions of
      this protein beyond its participation in microtubule nucleation. gamma-Tubulin
      expression is altered in various malignancies, and changes in the TUBG1 gene have
      been found in patients suffering from brain malformations. This review
      recapitulates the known functions of gamma-tubulin in cellular homeostasis and
      discusses the possible influence of the protein on disease development and
      cancer.

PMID- 30221016
TI  - On the use of kernel machines for Mendelian randomization.
AB  - Background: Properly adjusting for unmeasured confounders is critical for health
      studies in order to achieve valid testing and estimation of the exposure's causal
      effect on outcomes. The instrumental variable (IV) method has long been used in
      econometrics to estimate causal effects while accommodating the effect of
      unmeasured confounders. Mendelian randomization (MR), which uses genetic variants
      as the instrumental variables, is an application of the instrumental variable
      method to biomedical research fields, and has become popular in recent years. One
      often-used estimator of causal effects for instrumental variables and Mendelian
      randomization is the two-stage least square estimator (TSLS). The validity of
      TSLS relies on the accurate prediction of exposure based on IVs in its first
      stage. Results: In this note, we propose to model the link between exposure and
      genetic IVs using the least-squares kernel machine (LSKM). Some simulation
      studies are used to evaluate the feasibility of LSKM in TSLS setting.
      Conclusions: Our results show that LSKM based on genotype score or genotype can
      be used effectively in TSLS. It may provide higher power when the association
      between exposure and genetic IVs is nonlinear.

PMID- 30221015
TI  - Towards integrated oncogenic marker recognition through mutual information-based
      statistically significant feature extraction: an association rule mining based
      study on cancer expression and methylation profiles.
AB  - Background: Marker detection is an important task in complex disease studies.
      Here we provide an association rule mining (ARM) based approach for identifying
      integrated markers through mutual information (MI) based statistically
      significant feature extraction, and apply it to acute myeloid leukemia (AML) and
      prostate carcinoma (PC) gene expression and methylation profiles. Methods: We
      first collect the genes having both expression and methylation values in AML as
      well as PC. Next, we run Jarque-Bera normality test on the expression/methylation
      data to divide the whole dataset into two parts: one that ollows normal
      distribution and the other that does not follow normal distribution. Thus, we
      have now four parts of the dataset: normally distributed expression data,
      normally distributed methylation data, non-normally distributed expression data,
      and non-normally distributed methylated data. A feature-extraction technique,
      "mRMR" is then utilized on each part. This results in a list of top-ranked genes.
      Next, we apply Welch t-test (parametric test) and Shrink t-test (non-parametric
      test) on the expression/methylation data for the top selected normally
      distributed genes and non-normally distributed genes, respectively. We then use a
      recent weighted ARM method, "RANWAR" to combine all/specific resultant genes to
      generate top oncogenic rules along with respective integrated markers. Finally,
      we perform literature search as well as KEGG pathway and Gene-Ontology (GO)
      analyses using Enrichr database for in silico validation of the prioritized
      oncogenes as the markers and labeling the markers as existing or novel. Results:
      The novel markers of AML are {ABCB11??KRT17?} (i.e., ABCB11 as up-regulated, &
      KRT17 as down-regulated), and {AP1S1-?KRT17??NEIL2-?DYDC1?}) (i.e., AP1S1 and
      NEIL2 both as hypo-methylated, & KRT17 and DYDC1 both as down-regulated). The
      novel marker of PC is {UBIAD1 ?APBA2??C4orf31?} (i.e., UBIAD1 as up-regulated and
      hypo-methylated, & APBA2 and C4orf31 both as down-regulated and hyper
      methylated). Conclusion: The identified novel markers might have critical roles
      in AML as well as PC. The approach can be applied to other complex disease.

PMID- 30221018
TI  - A framework to quantify the strength of ecological links between an environmental
      stressor and final ecosystem services.
AB  - Anthropogenic stressors such as climate change, increased fire frequency, and
      pollution drive shifts in ecosystem function and resilience. Scientists generally
      rely on biological indicators of these stressors to signal that ecosystem
      conditions have been altered. However, these biological indicators are not always
      capable of being directly related to ecosystem components that provide benefits
      to humans and/or can be used to evaluate the cost-benefit of a change in health
      of the component (ecosystem services). Therefore, we developed the STEPS
      (STressor - Ecological Production function - final ecosystem Services) Framework
      to link changes in a biological indicator of a stressor to final ecosystem
      services. The STEPS framework produces "chains" of ecological components that
      explore the breadth of impacts resulting from the change of a stressor. Chains
      are comprised of the biological indicator, the ecological production function
      (EPF; which uses ecological components to link the biological indicator to a
      final ecosystem service), and the user group who directly uses, appreciates, or
      values the component. The framework uses a qualitative score (High, Medium, Low)
      to describe the Strength of Science (SOS) for the relationship between each
      component in the EPF. We tested the STEPS Framework within a workshop setting
      using the exceedance of critical loads of air pollution as a model stressor and
      the Final Ecosystem Goods and Services Classification System (FEGS-CS) to
      describe final ecosystem services. We identified chains for four modes of
      ecological response to deposition: aquatic acidification, aquatic eutrophication,
      terrestrial acidification, and terrestrial eutrophication. The workshop
      participants identified 183 unique EPFs linking a change in a biological
      indicator to a FEGS; and when accounting for the multiple beneficiaries, we ended
      with 1104 chains. The SOS scores were effective in identifying chains with the
      highest confidence ranking as well as those where more research is needed. The
      STEPS framework could be adapted to any system in which a stressor is modifying a
      biological component. The results of the analysis can be used by the social
      science community to apply valuation measures to multiple or selected chains,
      providing a comprehensive analysis of the effects of anthropogenic stressors on
      measures of human well-being.

PMID- 30221017
TI  - Levels of circulating follicular helper T cells, T helper 1 cells, and the
      prognostic significance of soluble form of CD40 ligand on survival in patients
      with alcoholic cirrhosis.
AB  - Background: Excessive drinkers (ED) and patients with alcoholic liver disease
      (ALD) are several times more susceptible to bacterial and viral infections and
      have a decrease in antibody responses to vaccinations. Follicular helper T (TFH)
      cells are essential to select B cells in the germinal center and to produce
      antibodies. TFH cells express both a membrane-associated and a soluble form of
      CD40 ligand (sCD40L); in which the latter form is released to circulation upon T
      cell activation. The effect of alcohol on TFH cells has not been studied.
      Objectives: The goals of this study are to determine the levels of TFH and T
      helper 1 (Th1) cells in ED and those with alcoholic cirrhosis (AC) when compared
      to healthy controls and to determine the prognostic significance of sCD40L in a
      cohort of patients with AC. Methods: Controls, ED, and those with AC were
      enrolled. Baseline demographic, laboratory tests, and peripheral blood
      mononuclear cells (PBMCs) were isolated and assessed via flow cytometry for TFH
      cells. In vitro study was performed to determine the ability of PBMCs to secrete
      interferon (IFN)-gamma upon stimulation. Serum sCD40L were also determined and
      its prognostic significance was tested in a cohort of AC patients. Results: The
      levels of circulating TFH (cTFH) cells were significantly lower in peripheral
      blood of subjects with ED and AC compared to controls (P<0.05). IFN-gamma
      secretion from PBMCs upon stimulation was also lower in ED and those with
      cirrhosis. Serum sCD40L was significantly lower in ED and AC when compared to
      that in controls (P<0.0005). Its level was an independent predictor of mortality.
      Conclusions: Patients with AC had significantly lower level of cTFH and sCD40L.
      The level of sCD40L was an independent predictor of mortality in these patients.

PMID- 30221020
TI  - Unexpected intraabdominal hemorrhage due to segmental arterial mediolysis
      following subarachnoid hemorrhage: A case of ruptured intracranial and
      intraabdominal aneurysms.
AB  - Background: Segmental arterial mediolysis (SAM) is an uncommon vascular disease,
      which manifests as catastrophic intraabdominal hemorrhage caused by rupture of
      visceral dissecting aneurysms in most cases. The etiology of SAM is still
      unclear, but SAM may be a vasospastic disorder and the responsible pressor agent
      is norepinephrine. Recently, abdominal SAM coexisting with intracranial
      dissecting aneurysms has been reported, but the relationship between
      intraabdominal and intracranial aneurysms in SAM remains unclear, as no cases of
      concomitant abdominal SAM and ruptured intracranial saccular aneurysm have been
      reported. Case Description: A 49-year-old woman underwent emergent clipping for a
      ruptured saccular aneurysm at the left C1 portion of the internal carotid artery.
      Intraoperatively, norepinephrine was continuously administered intravenously
      under general anesthesia. Four days after the subarachnoid hemorrhage (SAH), the
      patient suddenly developed shock due to massive hematoma in the abdominal cavity.
      Imaging showed multiple aneurysms involving the splenic artery, gastroduodenal
      artery, common hepatic artery, and superior mesenteric artery. Coil embolization
      of the splenic artery was performed immediately to prevent bleeding. Subsequent
      treatment for cerebral vasospasm following SAH was performed with prevention of
      hypertension, and the patient recovered with left temporal lobe infarction. The
      diagnosis was abdominal SAM based on the clinical, imaging, and laboratory
      findings. Conclusion: Norepinephrine release induced by SAH and/or iatrogenic
      administration of norepinephrine may have promoted abdominal SAM in this case.
      Abdominal SAM may occur subsequent to rupture of ordinary saccular aneurysm, and
      may provoke catastrophic abdominal hemorrhage in the spasm stage after SAH.

PMID- 30221019
TI  - The Longitudinal Relations between Dimensions of Community Violence Exposure and
      Developmental Outcomes among Adolescent Ethnic Minority Males.
AB  - Objective: Community violence exposure is multi-dimensional, yet the majority of
      studies examining the relation of exposure and developmental outcomes employ
      measures that collapse a wide range of experiences into a global summed scale.
      Building on research conducted in child maltreatment indicating that the impact
      of exposure varies as a function of the nature of maltreatment, the present study
      examines the contribution of dimensions of exposure to community violence (i.e.,
      type - hearing about violence, witnessing violence, victimization - and
      relationship to perpetrator) on three areas of adolescent functioning:
      depression, aggression, and attention problems. Method: Longitudinal data was
      gathered from a sample of racial/ethnic minority male adolescents (N = 246)
      living in impoverished urban neighborhoods. Multiple regression analyses assessed
      the relation between dimensions and outcomes cross-sectionally and
      longitudinally. Results: In line with findings from maltreatment, dimensions of
      violence exposure mattered differentially for developmental outcomes when
      examined concurrently. However, when relations are examined longitudinally,
      controlling for initial levels of functioning, the majority these relations
      disappear. Conclusions: Assessing exposure to specific dimensions of exposure
      might improve understanding of adolescent concurrent, but not later functioning.
      Findings underscore the value of prospective data when examining the impact of
      dimensions of community violence exposure on functioning.

PMID- 30221021
TI  - What happened to "Patient first" and "Do no harm" medical principles?

PMID- 30221022
TI  - Awake craniotomy without sedation in treatment of patients with lesional
      epilepsy.
AB  - Background: The use of awake craniotomy for surgical treatment of epilepsy was
      applied in surgery of convexital tumors, arteriovenous malformations, some
      superficial aneurysms, and stereotactic neurosurgery. The aim of this study was
      to show the advantages of awake craniotomy without sedation, accompanied by
      intraoperative neurophysiological monitoring in patients with symptomatic
      epilepsy. Methods: This article describes the results of surgical treatment in 41
      patients with various pathologies; 31 among them suffered from epilepsy. Results:
      Most frequently, the pathological foci were located in frontal and parietal lobes
      nearby eloquent brain areas. Irrespective of damage location, simple partial and
      complex partial seizures were seen almost with the same frequency. Intraoperative
      mapping of eloquent cortical areas and subcortical tracts without sedation
      resulted in total resection of pathological area in 75% of cases with low rate of
      permanent neurological deficit (two patients). Minor perioperative complications,
      including the decrease in blood pressure in six patients and intraoperative
      convulsions in two patients, were handled and did not led to operation
      termination or anesthesia conversion. Excellent seizures control (Engel 1) was
      achieved in 80% of patients with available catamnesis. Conclusion: Thus, the
      proposed method allows eliminating the complications associated with sedation and
      provides radical resection of pathological epileptogenic foci with low
      complication rate.

PMID- 30221023
TI  - Rare case of meningeal tuberculoma mimicking meningioma in term pregnancy and its
      management.

PMID- 30221024
TI  - Prognostic factors in brain metastases from laryngeal squamous cell carcinoma:
      Case report and review.
AB  - Background: Brain metastases from laryngeal squamous cell carcinoma (SCC) are
      rare, and there are no standardized treatments. Here we reported on a case of
      brain metastasis from laryngeal SCC and performed a literature review on these
      cases. Moreover, by plotting Kaplan-Meier curves, we carried out a survival
      analysis to provide an estimation of overall survival (OS) and to find possible
      prognostic factors. Case Description: A 65-year-old male was admitted to our
      department with a large left occipital lesion. Three years ago, the patient had
      undergone total laryngectomy with bilateral neck dissection with a diagnosis of a
      poor differentiated SCC. The occipital lesion was totally removed. A diagnosis of
      a brain metastasis from laryngeal SCC was made. The patient was submitted to
      adjuvant chemotherapy and radiation therapy. He is in good clinical conditions at
      7-month follow-up with a still ongoing chemotherapy. From survival analysis, we
      have found that surgery and/or radiochemotherapy increase the OS of these
      patients compared with untreated cases. Moreover, Karnofsky performance status
      (KPS) score >=70 and recursive partitioning analysis (RPA) classes I and II were
      associated with better OS in these patients. Conclusion: Brain metastases from
      laryngeal SCC are rare. This is the first study in which a survival analysis of
      these cases has been performed. Surgery and/or radio-chemotherapy increase the
      survival of these patients compared with untreated cases. Moreover, KPS score and
      RPA class affect the outcome of these patients.

PMID- 30221025
TI  - Resection and imbrication of symptomatic sacral Tarlov cysts: A case report and
      review of the literature.
AB  - Background: Symptomatic Tarlov cysts are extremely rare, and there is no
      consensus regarding their optimal surgical management. Here, we encountered a
      patient with a symptomatic sacral Tarlov cyst and reviewed the appropriate
      literature. Case Description: A 40-year-old male presented with right lower
      extremity pain and hypoesthesia in the right S2 dermatome. The lumbosacral MR
      demonstrated a right S2 Tarlov cyst compressing the S2-S3 perineural sheaths.
      After the patient underwent microscopic cystectomy with obliteration of the
      subarachnoid connection to the cyst, the patient's symptoms resolved. Here, we
      reviewed our operative approach, and others proposed in the literature for the
      surgical management of these lesions. Conclusions: Here, we present a 40-year-old
      male who was symptomatic from a right S2 Tarlov cyst compressing the S2-S3
      perineural sheaths and successfully underwent microscopic cystectomy with
      obliteration of the subarachnoid connection. Additionally, the appropriate Tarlov
      cyst literature was reviewed.

PMID- 30221026
TI  - PReP: Path-Based Relevance from a Probabilistic Perspective in Heterogeneous
      Information Networks.
AB  - As a powerful representation paradigm for networked and multi-typed data, the
      heterogeneous information network (HIN) is ubiquitous. Meanwhile, defining proper
      relevance measures has always been a fundamental problem and of great pragmatic
      importance for network mining tasks. Inspired by our probabilistic interpretation
      of existing path-based relevance measures, we propose to study HIN relevance from
      a probabilistic perspective. We also identify, from real-world data, and propose
      to model cross-meta-path synergy, which is a characteristic important for
      defining path-based HIN relevance and has not been modeled by existing methods. A
      generative model is established to derive a novel path-based relevance measure,
      which is data-driven and tailored for each HIN. We develop an inference algorithm
      to find the maximum a posteriori (MAP) estimate of the model parameters, which
      entails non-trivial tricks. Experiments on two real-world datasets demonstrate
      the effectiveness of the proposed model and relevance measure.

PMID- 30221027
TI  - Mechanistic Complexity of Methane Oxidation with H2O2 by Single-Site Fe/ZSM-5
      Catalyst.
AB  - Periodic density functional theory (DFT) calculations were carried out to
      investigate the mechanism of methane oxidation with H2O2 over the defined Fe
      sites in Fe/ZSM-5 zeolite. The initial Fe site is modeled as a [(H2O)2-Fe(III)
      (MUO)2-Fe(III)-(H2O)2]2+ extraframework cluster deposited in the zeolite pore and
      charge-compensated by two anionic lattice sites. The activation of this cluster
      with H2O2 gives rise to the formation of a variety of Fe(III)-oxo and Fe(IV)-oxo
      complexes potentially reactive toward methane dissociation. These sites are all
      able to promote the first C-H bond cleavage in methane by following three
      possible reaction mechanisms: namely, (a) heterolytic and (b) homolytic methane
      dissociation as well as (c) Fenton-type reaction involving free OH radicals as
      the catalytic species. The C-H activation step is followed by formation of MeOH
      and MeOOH and regeneration of the active site. The Fenton-type path is found to
      proceed with the lowest activation barrier. Although the barriers for the
      alternative heterolytic and homolytic pathways are found to be somewhat higher,
      they are still quite favorable and are expected to be feasible under reaction
      conditions, resulting ultimately in MeOH and MeOOH products. H2O2 oxidant
      competes with CH4 substrate for the same sites. Since the oxidation of H2O2 to O2
      and two [H+] is energetically more favorable than the C-H oxofunctionalization,
      the overall efficiency of the latter target process remains low.

PMID- 30221030
TI  - Operando Insights into CO Oxidation on Cobalt Oxide Catalysts by NAP-XPS, FTIR,
      and XRD.
AB  - Cobalt oxide Co3O4 has recently emerged as promising, noble metal-free catalyst
      for oxidation reactions but a better understanding of the active catalyst under
      working conditions is required for further development and potential
      commercialization. An operando approach has been applied, combining near ambient
      (atmospheric) pressure X-ray photoelectron spectroscopy (NAP-XPS), Fourier
      transform infrared spectroscopy (FTIR), or X-ray diffraction (XRD) with
      simultaneous catalytic tests of CO oxidation on Co3O4, enabling one to monitor
      surface and bulk states under various reaction conditions (steady-state and
      dynamic conditions switching between CO and O2). On the basis of the surface
      specific chemical information a complex network of different reaction pathways
      unfolded: Mars-van-Krevelen (MvK), CO dissociation followed by carbon oxidation,
      and formation of carbonates. A possible Langmuir-Hinshelwood (LH) pathway cannot
      be excluded because of the good activity when no oxygen vacancies were detected.
      The combined NAP-XPS/FTIR results are in line with a MvK mechanism above 100 
      degrees C, involving the Co3+/Co2+ redox couple and oxygen vacancy formation.
      Under steady state, the Co3O4 surface appeared oxidized and the amount of reduced
      Co2+ species at/near the surface remained low up to 200  degrees C. Only in pure
      CO, about 15% of surface reduction were detected, suggesting that the active
      sites are a minority species. The operando spectroscopic studies also revealed
      additional reaction pathways: CO dissociation followed by carbon reoxidation and
      carbonate formation and its decomposition. However, due to their thermal
      stability in various atmospheres, the carbonates are rather spectators and also
      CO dissociation seems a minor route. This study thus highlights the benefits of
      combining operando surface sensitive techniques to gain insight into
      catalytically active surfaces.

PMID- 30221028
TI  - Tuning the Electrocatalytic Performance of Ionic Liquid Modified Pt Catalysts for
      the Oxygen Reduction Reaction via Cationic Chain Engineering.
AB  - Modifying Pt catalysts using hydrophobic ionic liquids (ILs) has been
      demonstrated to be a facile approach for boosting the performance of Pt catalysts
      for the oxygen reduction reaction (ORR). This work aims to deepen the
      understanding and initiate a rational molecular tuning of ILs for improved
      activity and stability. To this end, Pt/C catalysts were modified using a variety
      of 1-methyl-3-alkylimidazolium bis(trifluoromethanesulfonyl)imide ([C n
      C1im][NTf2], n = 2-10) ILs with varying alkyl chain lengths in imidazolium
      cations, and the electrocatalytic properties (e.g., electrochemically active
      surface area, catalytic activity, and stability) of the resultant catalysts were
      systematically investigated. We found that ILs with long cationic chains (C6,
      C10) efficiently suppressed the formation of nonreactive oxygenated species on
      Pt; however, at the same time they blocked active Pt sites and led to a lower
      electrochemically active surface area. It is also disclosed that the catalytic
      activity strongly correlates with the alkyl chain length of cations, and a
      distinct dependence of intrinsic activity on the alkyl chain length was
      identified, with the maximum activity obtained on Pt/C-[C4C1im][NTf2]. The
      optimum arises from the counterbalance between more efficient suppression of
      oxygenated species formation on Pt surfaces and more severe passivation of Pt
      surfaces with elongation of the alkyl chain length in imidazolium cations.
      Moreover, the presence of an IL can also improve the electrochemical stability of
      Pt catalysts by suppressing the Pt dissolution, as revealed by combined identical
      location transmission electron microscopy (TEM) and in situ inductively coupled
      plasma mass spectrometry (ICP-MS) analyses.

PMID- 30221029
TI  - Unraveling the H2 Promotional Effect on Palladium-Catalyzed CO Oxidation Using a
      Combination of Temporally and Spatially Resolved Investigations.
AB  - The promotional effect of H2 on the oxidation of CO is of topical interest, and
      there is debate over whether this promotion is due to either thermal or chemical
      effects. As yet there is no definitive consensus in the literature. Combining
      spatially resolved mass spectrometry and X-ray absorption spectroscopy (XAS), we
      observe a specific environment of the active catalyst during CO oxidation, having
      the same specific local coordination of the Pd in both the absence and presence
      of H2. In combination with Temporal Analysis of Products (TAP), performed under
      isothermal conditions, a mechanistic insight into the promotional effect of H2
      was found, providing clear evidence of nonthermal effects in the hydrogen
      promoted oxidation of carbon monoxide. We have identified that H2 promotes the
      Langmuir-Hinshelwood mechanism, and we propose this is linked to the increased
      interaction of O with the Pd surface in the presence of H2. This combination of
      spatially resolved MS and XAS and TAP studies has provided previously unobserved
      insights into the nature of this promotional effect.

PMID- 30221031
TI  - Biocatalytic Aldol Addition of Simple Aliphatic Nucleophiles to Hydroxyaldehydes.
AB  - Asymmetric aldol addition of simple aldehydes and ketones to electrophiles is a
      cornerstone reaction for the synthesis of unusual sugars and chiral building
      blocks. We investigated d-fructose-6-phosphate aldolase from E. coli (FSA) D6X
      variants as catalysts for the aldol additions of ethanal and nonfunctionalized
      linear and cyclic aliphatic ketones as nucleophiles to nonphosphorylated
      hydroxyaldehydes. Thus, addition of propanone, cyclobutanone, cyclopentanone, or
      ethanal to 3-hydroxypropanal or (S)- or (R)-3-hydroxybutanal catalyzed by FSA D6H
      and D6Q variants furnished rare deoxysugars in 8-77% isolated yields with high
      stereoselectivity (97:3 dr and >95% ee).

PMID- 30221032
TI  - A ribonucleoprotein octamer for targeted siRNA delivery.
AB  - Hurdles in cell-specific delivery of small interfering RNA (siRNA) in vivo hinder
      the clinical translation of RNA interference (RNAi). A fundamental problem
      concerns conflicting requirements for the design of the delivery vehicles:
      cationic materials facilitate cargo condensation and endosomolysis, yet hinder in
      vivo targeting and colloidal stability. Here, we describe a self-assembled,
      compact (~30 nm) and biocompatible ribonucleoprotein-octamer nanoparticle that
      achieves endosomal destabilization and targeted delivery. The protein octamer
      consists of a poly(ethylene glycol) scaffold, a sterically masked endosomolytic
      peptide, and a double-stranded RNA-binding domain, provides a discrete number of
      siRNA loading sites and a high siRNA payload (> 30 wt%), and offers flexibility
      in both siRNA and targeting-ligand selection. We show that a ribonucleoprotein
      octamer against the polo-like kinase 1 (Plk1) gene and bearing a ligand that
      binds to prostate specific membrane antigen (PSMA) leads to efficient gene
      silencing in prostate tumour cells in vitro and when intravenously injected in
      mouse models of prostate cancer. The octamer's versatile nanocarrier design
      should offer opportunities for the clinical translation of therapies based on
      intracellularly acting biologics.

PMID- 30221033
TI  - The Earning and Spending Habits of Male Sex Workers in Lima, Peru.
AB  - Over the past decade, data have identified male sex work as a potentially viable
      economic decision; despite this, male sex workers (MSWs) continue to be perceived
      as group with access to few assets and resources. Using data from a pilot skills-
      building intervention for MSWs in Lima, Peru, an analysis of the economic
      characteristics of 209 MSWs is presented. The majority reported livable incomes
      with median earnings of US$250 per month, 83% earning above the urban poverty
      line. Interestingly, non-sex work was also an important source of income,
      especially for the high-earning MSWs. Spending data revealed that a large portion
      of income went to necessities (55%), luxuries (11%), and gifts (11%), with less
      toward savings (5%) and studies (1%). Such data on MSWs' earnings and spending,
      which suggest that a lack of overall income is not the MSW's main impediment to
      escaping poverty, could direct future poverty alleviation and health improvement
      programs in this key population.

PMID- 30221035
TI  - Temporality of heparin-induced antibodies: a retrospective study in outpatients
      undergoing hemodialysis on unfractionated heparin.
AB  - Background: Heparin-induced antibodies (HIA) are responsible for causing heparin
      induced thrombocytopenia and thrombosis. Research has shown that the temporality
      of heparin-induced antibodies does not follow the classic immunologic response.
      The immunobiology of HIA generation remains unclear with varying in vitro and in
      vivo data. Outpatients undergoing hemodialysis (HD) are exposed to heparin
      chronically. The HIA immune response can therefore be investigated in vivo in
      this population. Methods: We examined the time between the start of HD using
      unfractionated heparin and HIA levels in 212 outpatients during a 6-year period.
      Antibodies were detected on enzyme-linked immunosorbent assay. HIA levels were
      analyzed to determine significance of the trend over time. HIA subgroups were
      also analyzed for correlation with subsequent thrombotic events and platelet
      count during follow up. Results: Overall, the HIA response in HD was found to
      peak early with waning antibody response despite continued exposure to heparin.
      The peak prevalence of a strong immune response (optical density > 1.000) was
      early and short lived, while weaker immune response (optical density 0.400-1.000)
      persisted for the first 6 months then declined. The mean follow-up time per
      patient was 2.3 +/- 1.4 years. Despite circulating HIA, including high titers, no
      patients developed HIT in this sample. There was no association between HIA and
      thrombocytopenia. There was increased incidence of thrombosis in patients with
      strong HIA compared to other groups, but this did not achieve statistical
      significance. Conclusions: The data suggest a significant temporal pattern of HIA
      in outpatients undergoing HD using unfractionated heparin. Positive HIA was not
      found to be significantly associated with thrombocytopenia or thrombosis risk in
      these patients. However, while not achieving statistical significance, subsequent
      thrombotic events occurred most frequently in the strong positive HIA group
      (optical density > 1.000). Further research into HIA and risk of thrombosis in
      this population is needed.

PMID- 30221036
TI  - Heating it up: Oncolytic viruses make tumors 'hot' and suitable for checkpoint
      blockade immunotherapies.
AB  - Immune checkpoint blockade is less efficient in patients bearing immunologically
      'cold' tumors. Oncolytic viruses, which were originally discovered for their
      ability to preferentially kill malignant cells, can recondition the tumor
      microenvironment. Supporting this hypothesis, two new studies published in
      Science Translational Medicine show that adjuvant-like activities of oncolytic
      viruses make brain and breast tumors 'hot' and sensitize them for subsequent
      immune checkpoint blockade.

PMID- 30221037
TI  - Perspectives of Fc engineered antibodies in CD19 targeting immunotherapies in
      pediatric B-cell precursor acute lymphoblastic leukemia.
AB  - CD19 immunotherapies based on T cells opened new avenues in the treatment of
      pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, Fc
      engineered CD19 antibodies may also bear great potential. In light of recent
      preclinical and clinical data, perspectives of such antibodies designed for
      improved effectiveness in BCP-ALL are presented.

PMID- 30221039
TI  - Stereotactic body radiation therapy and thymosin alpha-1-induced anti-tumor
      effects in heavily pretreated, metastatic esophageal squamous cell carcinoma
      patients.
AB  - This study investigated the anti-tumor effects of stereotactic body radiation
      therapy (SBRT) with thymosin alpha-1 (Talpha1) in heavily pretreated, metastatic
      esophageal squamous cell carcinoma (mESCC) patients. Thirty-one patients with at
      least 2 metastatic sites were enrolled. SBRT was delivered with a daily fraction
      of 5.0 Gy for a total dosage of 25 Gy over one week to one metastatic lesion.
      Concurrent Talpha1 (1.6mg subcutaneously) was administered twice a week with an
      interval of 3-4 days until tumor progression of other documented metastatic
      lesions. Anti-tumor effects (the primary endpoint) were evaluated by assessing
      the CT/MRI response of other distinct measurable lesions. Secondary endpoints
      included treatment safety, survival outcomes and immune-related blood parameters.
      This study was registered at ClinicalTrials.gov (NCT 02545751). Partial response
      occurred in three (9.7%) patients, and 11 (35.5%) patients had stable metastatic
      disease, which yielded a metastatic-lesion control rate of 45.2%. Seventeen
      (54.8%) patients were documented to have progressive disease in other metastatic
      lesions. The median overall survival and abscopal progression free survival
      (APFS) times were 5.2 and 2.9 months, respectively. Significant differences in
      survival outcomes were observed between the abscopal control group (without
      progression in the abscopal lesions at 12 weeks) and the non-control group (P =
      0.035 and 0.044, respectively). Treatment-related toxicity was acceptable, and no
      grade 4 acute toxicity occurred. Immunomonitoring of lymphocytes showed that the
      proportion of CD8+ T cells after treatment was significantly different between
      the abscopal control group and the non-control group (P=0.047). In conclusion,
      the combination of SBRT with Talpha1 produced encouraging effects in heavily
      pretreated, mESCC patients and further research on radiation enhanced
      immunotherapy is warranted.

PMID- 30221038
TI  - Evolution of melanoma cross-resistance to CD8+ T cells and MAPK inhibition in the
      course of BRAFi treatment.
AB  - The profound but frequently transient clinical responses to BRAFV600 inhibitor
      (BRAFi) treatment in melanoma emphasize the need for combinatorial therapies.
      Multiple clinical trials combining BRAFi and immunotherapy are under way to
      further enhance therapeutic responses. However, to which extent BRAFV600
      inhibition may affect melanoma immunogenicity over time remains largely unknown.
      To support the development of an optimal treatment protocol, we studied the
      impact of prolonged BRAFi exposure on the recognition of melanoma cells by T
      cells in different patient models. We demonstrate that autologous CD8+ tumor
      infiltrating lymphocytes (TILs) efficiently recognized short-term (3, 7 days)
      BRAFi-treated melanoma cells but were less responsive towards long-term (14, 21
      days) exposed tumor cells. Those long-term BRAFi-treated melanoma cells showed a
      non-proliferative dedifferentiated phenotype and were less sensitive to four out
      of five CD8+ T cell clones, present in the preexisting TIL repertoire, of which
      three recognized shared antigens (Tyrosinase, Melan-A and CSPG4) and one being
      neoantigen-specific. Only a second neoantigen was steadily recognized independent
      of treatment duration. Notably, in all cases the impaired T cell activation was
      due to a time-dependent downregulation of their respective target antigens.
      Moreover, combinatorial treatment of melanoma cells with BRAFi and an inhibitor
      of its downstream kinase MEK had similar effects on T cell recognition. In
      summary, MAP kinase inhibitors (MAPKi) strongly alter the tumor antigen
      expression profile over time, favoring evolution of melanoma variants cross
      resistant to both T cells and MAPKi. Our data suggest that simultaneous treatment
      with MAPKi and immunotherapy could be most effective for tumor elimination.

PMID- 30221040
TI  - A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3
      T-cell engager (BiTE(r)) antibody construct, in patients with refractory solid
      tumors.
AB  - We assessed the tolerability and antitumor activity of solitomab, a bispecific T
      cell engager (BiTE(r)) antibody construct targeting epithelial cell adhesion
      molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to
      standard therapy received solitomab as continuous IV infusion in a phase 1 dose
      escalation study with six different dosing schedules. The primary endpoint was
      frequency and severity of adverse events (AEs). Secondary endpoints included
      pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. Sixty
      five patients received solitomab at doses between 1 and 96 ug/day for >=28 days.
      Fifteen patients had dose-limiting toxicities (DLTs): eight had transient
      abnormal liver parameters shortly after infusion start or dose escalation (grade
      3, n = 4; grade 4, n = 4), and one had supraventricular tachycardia (grade 3);
      all events resolved with solitomab discontinuation. Six patients had a DLT of
      diarrhea: four events resolved (grade 3, n = 3; grade 4, n = 1), one (grade 3)
      was ongoing at the time of treatment-unrelated death, and one (grade 3)
      progressed to grade 5 after solitomab discontinuation. The maximum tolerated dose
      was 24 ug/day. Overall, 95% of patients had grade >=3 treatment-related AEs,
      primarily diarrhea, elevated liver parameters, and elevated lipase. Solitomab
      half-life was 4.5 hours; serum levels plateaued within 24 hours. One unconfirmed
      partial response was observed. In this study of a BiTE(r) antibody construct
      targeting solid tumors, treatment of relapsed/refractory EpCAM-positive solid
      tumors with solitomab was associated with DLTs, including severe diarrhea and
      increased liver enzymes, which precluded dose escalation to potentially
      therapeutic levels.

PMID- 30221034
TI  - 1-Aminobenzotriazole: A Mechanism-Based Cytochrome P450 Inhibitor and Probe of
      Cytochrome P450 Biology.
AB  - 1-Aminobenzotriazole (1-ABT) is a pan-specific, mechanism-based inactivator of
      the xenobiotic metabolizing forms of cytochrome P450 in animals, plants, insects,
      and microorganisms. It has been widely used to investigate the biological roles
      of cytochrome P450 enzymes, their participation in the metabolism of both
      endobiotics and xenobiotics, and their contributions to the metabolism-dependent
      toxicity of drugs and chemicals. This review is a comprehensive evaluation of the
      chemistry, discovery, and use of 1-aminobenzotriazole in these contexts from its
      introduction in 1981 to the present.

PMID- 30221041
TI  - Intratumoral injection of activated B lymphoblast in combination with PD-1
      blockade induces systemic antitumor immunity with reduction of local and distal
      tumors.
AB  - In spite of the success of PD-1 blocking antibodies in the clinic their benefits
      are still restricted to a small fraction of patients. Immune-desert tumors and/or
      the highly immunosuppressive tumor milieu might hamper the success of PD-1/PD-L1
      blocking therapies into a broader range of cancer patients. Although still under
      debate, there is a cumulative body of evidence that indicates B tumor
      infiltrating lymphocytes are a good prognostic marker in most types of cancer,
      especially in those that form ectopic lymphoid tissue structures. Taking this
      into account, we reason that the adoptive transfer of activated B lymphoblasts
      (ABL) in the tumor could be a feasible therapeutic approach to shift the
      immunosuppressive tumor microenvironment into an immune-permissive one. In this
      work we show the antitumor effect of ABL therapy in two different tumor models:
      colon carcinoma (CT26) and melanoma (B16/F10). The ABL transfer in the most
      relevant non-immunogenic B16/F10 melanoma model depicts synergism with anti-PD-1
      antibody therapy. Furthermore, systemic antitumor immunity was detected in mice
      treated with PD-1 antibody/ABL combination which was able to reach distal
      metastatic lesions.

PMID- 30221042
TI  - Superior efficacy and similar safety of double dose anakinra in Erdheim-Chester
      disease after single dose treatment.
AB  - Objectives. In Erdheim-Chester disease (ECD), the empirical single dose (SD, 100
      mg/day) anakinra sometimes induces only partial responses. Since SD is usually
      well tolerated, doubling the dose might improve response while maintaining an
      acceptable safety profile. Methods. A retrospective analysis was performed of
      outcomes under double-dose (DD) of anakinra in 4 ECD patients who did not exhibit
      a complete response (CR) under SD treatment. Bone, retroperitoneal,
      neurologic/orbital, peritoneal, pericardial, right atrium, and pleural
      involvements were recorded. CR, partial response (PR), stable disease,
      progressive disease (PD) and tolerance of DD were assessed. Results. SD treatment
      was a second or third line treatment in three patients after interferon-therapy
      failure. Two patients, including one with a BRAF mutation, achieved a CR and one
      patient with a NRAS mutation achieved a PR with DD treatment. The fourth patient,
      wild-type for both genes, did not respond to a first DD treatment, but then
      achieved CR under SD associated with a reduced dose of vemurafenib (960 mg/d).
      Bone and retroperitoneal lesions partially improved on imaging with SD in all
      patients, but were further improved under DD with two patients achieving CR. With
      SD treatment, two patients with right atrial masses showed sustained CR. Under DD
      treatment, two patients with massive serositis refractory to SD, showed PR.
      Conclusion. DD improved the response to anakinra and lead to two CRs and a PR in
      three out of four ECD patients, with minor and comparable side-effects to those
      of SD, while failures were essentially related to massive serositis.

PMID- 30221043
TI  - delta-Catenin peptide vaccines repress hepatocellular carcinoma growth via CD8+ T
      cell activation.
AB  - As classical therapy method of advanced hepatocellular carcinoma (HCC) is not
      effective enough, HCC immunotherapy is a hot spot for research in recent years.
      Although in recent years, immune checkpoint inhibitors are focused in cancer
      therapy, vaccines and adoptive cell therapy (ACT), as traditional immunotherapy
      methods for HCC are still promising. We found that delta-Catenin might be a new
      tumor-associated antigen for HCC, for it could be upregulated as a stress
      associated protein under hypoxia and irradiation treatment. delta-Catenin peptide
      vaccines could inhibit the growth of subcutaneous hepatocellular tumors in vivo.
      According to our work, delta-Catenin peptide vaccines could stimulate the
      activation of cytotoxic T lymphocytes (CTLs) and enhance the infiltration of CD8+
      T cells into tumors. Moreover, delta-Catenin peptide vaccines could enhance the
      secretion of IFN-gamma and the killing of tumor cells by T cells.
      Mechanistically, delta-Catenin peptide vaccines, presented by antigen-presenting
      cells to T cells, could enhance the activation of T cells via MAPK/ERK signaling
      and the transcriptional factors Eomes and T-bet. Our research results indicate
      new potential peptide vaccines, which can be applied in clinical HCC therapy.

PMID- 30221044
TI  - Chemokine receptor engineering of T cells with CXCR2 improves homing towards
      subcutaneous human melanomas in xenograft mouse model.
AB  - Adoptive cell therapy (ACT) using in vitro expanded tumor infiltrating T
      lymphocytes (TILs) from biopsy material represents a highly promising treatment
      of disseminated cancer. A crucial prerequisite for successful ACT is sufficient
      recruitment of transferred lymphocytes to the tumor site; however, despite
      infusion of billions of lymphocytes, T cell infiltration into the tumor post ACT
      is limited. By PCR and Luminex analyses we found that a majority of malignant
      melanoma (MM) cell lines expressed chemokines CXCL1/Groalpha, CXCL8/IL-8,
      CXCL12/SDF-1 and CCL2. Concerning expression of the corresponding receptors on T
      cells, only the IL-8 receptor, CXCR2, was not expressed on T cells. CXCR2 was
      therefore expressed in T cells by lentiviral transduction, and shown to lead to
      ligand specific transwell migration of engineered T cells, as well as increased
      migration towards MM conditioned medium. In vivo homing was assessed in a
      xenograft NOG mouse model. Mice with subcutaneous human melanoma were treated
      with MAGE-A3 specific T cells transduced with either CXCR2 or MOCK. Transducing T
      cells carrying the MAGE-A3a3a high affinity T cell receptor with CXCR2 increased
      tumor infiltration. Flow cytometry analysis 7 days after ACT showed a doubling in
      CD3+ T cells in tumor digest of mice receiving CXCR2 transduced T cells compared
      to MOCK treated mice, a finding confirmed by immunohistochemistry. In conclusion,
      our CXCR2 transduced T cells are functional in vitro and transduction with CXCR2
      increases in vivo homing of T cells to tumor site.

PMID- 30221045
TI  - Detailed analysis of adenosine A2a receptor (ADORA2A) and CD73 (5'-nucleotidase,
      ecto, NT5E) methylation and gene expression in head and neck squamous cell
      carcinoma patients.
AB  - Background: The adenosine A2a receptor (A2aR) and the adenosine synthesizing
      enzyme CD73 have recently evolved as a novel immunotherapeutic target. However,
      little is known about epigenetic modification of the encoding genes ADORA2A and
      NT5E. Methods: In the present study, we evaluated methylation at 23 loci of
      ADORA2A and 17 loci of NT5E with regard to transcriptional activity, human
      papilloma virus (HPV) status, immune cell infiltration, and outcome in a cohort
      of 279 head and neck squamous carcinoma (HNSCC) patients obtained from The Cancer
      Genome Atlas (TCGA). Methylation and mRNA expression were generated by the
      Infinium HumanMethylation450 BeadChip and Illumina HiSeq 2000 RNA Sequencing
      Version 2 analysis (Illumina, Inc., San Diego, CA, USA). HPV status was assessed
      by RNA-Seq data analysis of the viral genes E6 and E7. Results: Thirteen out of
      23 ADORA2A loci and 15/17 NT5E loci were significantly correlated with mRNA
      levels (p < 0.05). Inverse correlations were predominately found in promoter
      regions, while positive correlations were more profound at intragenic loci.
      ADORA2A hypermethylation was significantly associated with poor overall survival
      (OS, p <= 0.030), whereas NT5E hypomethylation was associated with decreased OS
      in HPV-positive tumors (p <= 0.024) and increased OS in HPV-negative HNSCC (p <=
      0.029). Further, we found significant correlations between methylation and immune
      cell infiltrates. Conclusion: Our data might point towards a significant role of
      the A2aR/CD73 axis during cancer progression in HNSCC.

PMID- 30221048
TI  - Driving Natural Killer cells toward the melanoma tumor battlefield: Autophagy as
      a valuable therapeutic target.
AB  - Natural Killer (NK) cell-based cancer immunotherapies were often disappointing in
      the clinic mostly due to insufficient NK cell infiltration into tumors. We found
      that targeting autophagy induced a massive infiltration of NK cells into melanoma
      tumors. These findings highlight autophagy inhibition as a cutting-edge approach
      to fully exploit the anti-tumor properties of NK cells in a wide variety of
      cancer patients.

PMID- 30221047
TI  - Using a panel of multiple tumor-associated antigens to enhance autoantibody
      detection for immunodiagnosis of gastric cancer.
AB  - Autoantibodies against tumor-associated antigens (TAAs) are attractive non
      invasive biomarkers for detection of cancer due to their inherently stable in
      serum. Serum autoantibodies against 9 TAAs from gastric cancer (GC) patients and
      healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). A
      logistic regression model predicting the risk of being diagnosed with GC in the
      training cohort (n = 558) was generated and then validated in an independent
      cohort (n = 372). Area under the receiver operating characteristic curve (AUC)
      was used to assess the diagnostic performance. Finally, an optimal prediction
      model with 6 TAAs (p62, c-Myc, NPM1, 14-3-3xi, MDM2 and p16) showed a great
      diagnostic performance of GC with AUC of 0.841 in the training cohort and 0.856
      in the validation cohort. The proportion of subjects being correctly defined were
      78.49% in the training cohort and 81.99% in the validation cohort. This
      prediction model could also differentiate early-stage (stage I-II) GC patients
      from healthy controls with sensitivity/specificity of 76.60%/72.34% and
      80.56%/79.17% in the training and validation cohort, respectively, and the
      overall sensitivity/specificity for early-stage GC were 78.92%/74.70% when being
      combined with two cohorts. This prediction model presented no significant
      difference for the diagnostic accuracy between early-stage and late-stage (stage
      III - IV) GC patients. The model with 6 TAAs showed a high diagnostic performance
      for GC detection, particularly for early-stage GC. This study further supported
      the hypothesis that a customized array of multiple TAAs was able to enhance
      autoantibody detection in the immunodiagnosis of GC.

PMID- 30221046
TI  - Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer
      treated by nivolumab.
AB  - Immune checkpoint inhibitors, as nivolumab, are used in advanced non-small cell
      lung cancer (NSCLC). However, no associated biomarker is validated in clinical
      practice with this drug. We investigated herein immune-related blood markers in
      patients with advanced NSCLC treated with nivolumab. Plasma of 43 consecutive
      patients were prospectively collected at time of the diagnosis of cancer, at the
      initiation of nivolumab and at the first tumour evaluation (2 months).
      Concentrations of PD-L1 (sPD-L1), soluble PD-L2 (sPD-L2), Interleukine-2 (sIl-2),
      Interferon-gamma (sIFN-gamma), and Granzyme B (sGranB) were quantified by ELISA.
      Cell free RNA was quantified by Reverse Transcriptase -PCR), and plasmatic
      microRNAs (miRNAs) were evaluated by targeted sequencing. Expression of PD-L1 on
      tumour biopsies was performed by immunohistochemistry using E13LN. High sPD-L1 at
      2 months and increase of sPD-L1 concentrations were associated with poor response
      and absence of clinical benefit (nivolumab treatment less than 6 months). The
      variation of sPD-L1 concentrations were confirmed by RNA quantification. sPD-L1
      concentrations were not correlated with PD-L1 expression on corresponding tumour
      samples. Low sGranB at nivolumab initiation was also associated with poor
      response. High sPD-L1 and low sGranB were associated with poor progression-free
      survival (PFS) and overall survival (OS). Low sPD-L2, low sIl-2 and high sIFN
      gamma were associated with grade 3-4 toxicities. Finally, miRNA screening showed
      that patients with clinical benefit (n = 9) had down-expression of miRNA-320b and
      -375 compared to patients with early progression at 2 months (n = 9). In
      conclusion, our results highlight the interest of circulating biomarkers in
      patients treated with nivolumab.

PMID- 30221049
TI  - Heterologous vaccination targeting prostatic acid phosphatase (PAP) using DNA and
      Listeria vaccines elicits superior anti-tumor immunity dependent on CD4+ T cells
      elicited by DNA priming.
AB  - Background. Sipuleucel T, an autologous cell-based vaccine targeting prostatic
      acid phosphatase (PAP), has demonstrated efficacy for the treatment of advanced
      prostate cancer. DNA vaccines encoding PAP and live attenuated Listeria vaccines
      have entered clinical trials for patients with prostate cancer, and have
      advantages in terms of eliciting predominantly Th1-biased immunity. In this
      study, we investigated whether the immunogenicity and anti-tumor efficacy of a
      DNA and Listeria vaccine, each encoding PAP, could be enhanced by using them in a
      heterologous prime/boost approach. Methods. Transgenic mice expressing HLA-A2.01
      and HLA-DRB1*0101 were immunized alone or with a heterologous prime/boost
      strategy. Splenocytes were evaluated for MHC class I and II-restricted, PAP
      specific immune responses by IFNgamma ELISPOTs. Anti-tumor activity to a
      syngeneic, PAP-expressing tumor line was evaluated. Results. PAP-specific
      cellular immunity and anti-tumor activity were elicited in mice after
      immunization with DNA- or listeria-based vaccines. Greater CD4+ and CD8+
      responses, and anti-tumor responses, were elicited when mice were immunized first
      with DNA and boosted with Listeria, but not when administered in the opposite
      order. This was found to be dependent on CD4+ T cells elicited with DNA priming,
      and was not due to inflammatory signals by Listeria itself or due to B cells
      serving as antigen-presenting cells for DNA during priming. Conclusions.
      Heterologous prime/boost vaccination using DNA priming with Listeria boosting may
      provide better anti-tumor immunity, similar to many reports evaluating DNA
      priming with vaccines targeting foreign microbial antigens. These findings have
      implications for the design of future clinical trials.

PMID- 30221050
TI  - The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma.
AB  - Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in
      tumour biology, recent studies have demonstrated the presence of of CD4+ T cells,
      expressing both, Tbet and Foxp3. Although Tbet+Foxp3+ T cells are currently a
      subject of intense research, less is known about their biological function
      especially in cancer. Here we found a considerable accumulation of
      Tbet+Foxp3+CD4+ T cells, mediated by the immunosuppressive cytokine TGFbeta in
      the lungs of tumour bearing mice. This is in line with previous studies,
      demonstrating the important role of TGFbeta for the immunopathogenesis of cancer.
      By gathering results both in murine model and in human disease, we demonstrate
      that, the conversion of IFNgamma producing anti-tumoral T-bet+Th1 CD4+ T cells
      into immunosuppressive Tbet and Foxp3-PD1 co-expressing regulatory cells could
      represent an additional important mechanism of TGFbeta-mediated blockade of anti
      tumour immunity.

PMID- 30221051
TI  - Oncolytic vaccines increase the response to PD-L1 blockade in immunogenic and
      poorly immunogenic tumors.
AB  - Activation of immune checkpoint pathways and limited T- cell infiltration result
      in immunological escape of tumors. Although immune checkpoint inhibitors are
      currently approved for several types of cancers, the response rate is often
      limited by the lack of tumor specific T-cells within the malignant tissue.
      Therefore, new combinatorial strategies are needed to enhance the clinical
      benefit of immune checkpoint inhibitors. We have previously developed PeptiCRAd,
      an oncolytic vaccine platform capable of directing the immune response toward
      tumor epitopes. In this study, we evaluated whether the platform could be used to
      increase the response rate to checkpoint inhibitors in both highly immunogenic
      and poorly immunogenic tumors, such as melanoma and triple negative breast cancer
      (TNBC). We report here that anti-PD-L1 therapy in combination with PeptiCRAd
      significantly reduced the growth of melanomas and increased the response rate to
      checkpoint inhibition. In fact, we registered a higher rate of complete responses
      among mice treated with the combination. This approach promoted the presence of
      non-exhausted antigen-specific T-cells within the tumor in comparison to anti-PD
      L1 monotherapy. Furthermore, we found that targeting both MHC-I and II restricted
      tumor epitopes was necessary to decrease the growth of the poorly immunogenic
      TNBC model 4T1 and that combination with PD-L1 blockade increased the number of
      responders to checkpoint inhibition. Finally, the described strategy was
      validated in a translational in vitro model using HLA matched human PBMCs and
      tumor cell lines. Consistent to our previous results, improved cytotoxicity was
      observed with combination of PeptiCRAd and anti-PD-L1. These results demonstrate
      that oncolytic virus based cancer vaccine can significantly improve the response
      rate to checkpoint blocking antibodies in the context of immunogenic and non
      immunogenic tumors.

PMID- 30221052
TI  - Efficacy and safety of immune checkpoint inhibitors in non-small cell lung
      cancer.
AB  - Immune checkpoint inhibitors (ICIs) are new therapeutic strategies for non-small
      cell lung cancer (NSCLC). We aimed to quantitatively evaluate the efficacy and
      safety of ICIs in NSCLC. Pubmed, Embase, Cochrane Library, and Web of Science
      were searched for randomized clinical trials comparing ICIs with control
      therapies in NSCLC. Data were pooled according to Preferred Reporting Items for
      Systematic Reviews and Meta-analyses guidelines. A total of 12 trails comprising
      6,919 NSCLC patients were included in this meta-analysis. ICIs therapies
      significantly improved progression-free survival (PFS) (HR, 0.838; P < 0.001),
      overall survival (OS) (HR, 0.747; P < 0.001) and objective response rates (ORR)
      (RR, 1.311; P < 0.001) in NSCLC. Prognostic benefit was observed irrespective of
      age, sex, treatment line, performance status and histology. Survival improvement
      of ICIs was limited for NSCLC patients with non-smoker (PFS, P = 0.468; OS, P =
      0.317) or central nervous system (CNS) metastasis (PFS, P = 0.209; OS, P =
      0.090), or positive EGFR mutation (PFS, P = 0.083; OS, P = 0.522) or PD-L1
      expression level less than 5% (PFS, P = 0.370; OS, P = 0.047). The relative risks
      of all-grade and high-grade (>=3) anemia, neutropenia, leukopenia,
      thrombocytopenia, stomatitis, nausea, pyrexia, asthenia and neuropathy were all
      decreased in patients received ICIs compared with control therapies. This meta
      analysis provides clinical evidence that ICIs improve PFS, OS, and ORR in NSCLC
      with fewer adverse effects. Our data establish ICIs as a prefer treatment option
      for NSCLC patients with smoker, no CNS metastasis, wild type EGFR, and high PD-L1
      expression.

PMID- 30221053
TI  - The clinical significance of PD-L1 in advanced gastric cancer is dependent on
      ARID1A mutations and ATM expression.
AB  - Whether PD-L1 expression is associated with survival outcomes in gastric cancer
      (GC) is controversial. The inhibition of the PD-1/PD-L1 pathway is effective
      against genomically unstable tumors. Hypothesizing that also the clinical
      significance of PD-L1 might be dependent on the activation of molecular circuits
      ensuring genomic stability, we evaluated PD-L1 expression in tissue samples from
      72 advanced GC patients treated with first-line chemotherapy. Samples were
      already characterized for DNA damage repair (DDR) component expression (pATM,
      pChk1, pWee1, gamma-H2AX and pRPA2) along with mutations in DDR-linked genes
      (TP53 and ARID1A). Overall, PD-L1 expression was not associated with progression
      free survival (PFS) and overall survival (OS), independently on whether we
      considered its expression in tumor cells (PD-L1-TCs) or in the immune infiltrate
      (PD-L1-TILs). In subgroup analysis, positive PD-L1-TC immunostaining was
      associated with better PFS in patients whose tumors did not carry DDR activation
      (multivariate Cox: HR 0.34, 95%CI: 0.15-0.76, p = 0.008). This subset (DDRoff)
      was characterized by negative pATM expression or the presence of ARID1A
      mutations. Conversely, the relationship between PD-L1-TC expression and PFS was
      lost in a molecular scenario denoting DDR activation (DDRon), as defined by
      concomitant pATM expression and ARID1A wild-type form. Surprisingly, while PD-L1
      TC expression was associated with better OS in the DDRoff subset (multivariate
      Cox: HR 0.41, 95% CI: 0.17-0.96, p = 0.039), in the DDRon subgroup we observed an
      opposite impact on OS (multivariate Cox: HR 2.56, 95%CI: 1.06-6.16, p = 0.036).
      Thus, PD-L1-TC expression may impact survival outcomes in GC on the basis of the
      activation/inactivation of genome-safeguarding pathways.

PMID- 30221054
TI  - Microvesicles released from multiple myeloma cells are equipped with ectoenzymes
      belonging to canonical and non-canonical adenosinergic pathways and produce
      adenosine from ATP and NAD.
AB  - Multiple myeloma (MM) derives from malignant transformation of plasma cells (PC),
      which accumulate in the bone marrow (BM), where microenvironment supports tumor
      growth and inhibits anti-tumor immune responses. Adenosine (ADO), an
      immunosuppressive molecule, is produced within MM patients' BM by adenosinergic
      ectoenzymes, starting from ATP (CD39/CD73) or NAD+ [CD38/CD203a(PC-1)/CD73].
      These ectoenzymes form a discontinuous network expressed by different BM cells.
      We investigated the expression and function of ectoenzymes on microvesicles (MVs)
      isolated from BM plasma samples of patients with MM, using asymptomatic forms of
      monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM)
      as controls. The percentage of MVs expressing ectoenzymes at high levels was
      higher when derived from MM patients than controls. BM CD138+ PC from MM patients
      expressed high levels of all ectoenzymes. Paired MVs samples confirmed a higher
      percentage of MVs with high ectoenzymes expression in MM patients than controls.
      Pooled MVs from MM patients or controls were tested for ADO production. The
      catabolism of ATP, NAD+, ADPR and AMP to ADO was higher in MVs from MM patients
      than in those from controls. In conclusion, our results confirmed the hypothesis
      that MVs in MM niche are main contributor of ADO production. The ability of MVs
      to reach biological fluids strongly support the view that MVs may assume
      diagnostic and pathogenetic roles.

PMID- 30221055
TI  - Combination of dual mTORC1/2 inhibition and immune-checkpoint blockade
      potentiates anti-tumour immunity.
AB  - mTOR inhibition can promote or inhibit immune responses in a context dependent
      manner, but whether this will represent a net benefit or be contraindicated in
      the context of immunooncology therapies is less understood. Here, we report that
      the mTORC1/2 dual kinase inhibitor vistusertib (AZD2014) potentiates anti-tumour
      immunity in combination with anti-CTLA-4 (alphaCTLA-4), alphaPD-1 or alphaPD-L1
      immune checkpoint blockade. Combination of vistusertib and immune checkpoint
      blocking antibodies led to tumour growth inhibition and improved survival of MC
      38 or CT-26 pre-clinical syngeneic tumour models, whereas monotherapies were less
      effective. Underlying these combinatorial effects, vistusertib/immune checkpoint
      combinations reduced the occurrence of exhausted phenotype tumour infiltrating
      lymphocytes (TILs), whilst increasing frequencies of activated Th1 polarized T
      cells in tumours. Vistusertib alone was shown to promote a Th1 polarizing
      proinflammatory cytokine profile by innate primary immune cells. Moreover,
      vistusertib directly enhanced activation of effector T-cell and survival, an
      effect that was critically dependent on inhibitor dose. Therefore, these data
      highlight direct, tumour-relevant immune potentiating benefits of mTOR inhibition
      that complement immune checkpoint blockade. Together, these data provide a clear
      rationale to investigate such combinations in the clinic.

PMID- 30221056
TI  - S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis.
AB  - S100A4 plays important roles in tumor development and metastasis, but its role in
      regulating inflammation and colitis-associated tumorigenesis has not been well
      characterized. Here, we report that S100A4 expression was increased in
      azoxymethane (AOM) and dextran sulfate sodium (DSS) induced colorectal cancer
      (CRC) in mice. After AOM/DSS treatment, both S100A4-TK mice with the selective
      depletion of S100A4-expressing cells and S100A4-deficient (S100A4-/-) mice
      developed fewer and smaller tumors than wild-type (WT) control littermates.
      Furthermore, S100A4-/- mice were resistant to DSS-induced colitis, reduced
      infiltration of macrophages, and the diminished production of proinflammatory
      cytokines. Further studies revealed that reduced colon inflammation and
      colorectal tumor development in S100A4-/- mice were partly due to the dampening
      of nuclear factor (NF)-kappaB activation in macrophages. Furthermore, the
      administration of a neutralizing S100A4 antibody to WT mice significantly
      decreased AOM/DSS-induced colon inflammation and tumorigenesis. These results
      indicate that S100A4 amplifies an inflammatory microenvironment that promotes
      colon tumorigenesis and provides a promising therapeutic strategy for treatment
      of inflammatory bowel disease and prevention of colitis-associated colorectal
      carcinogenesis.

PMID- 30221057
TI  - Adoptive immunotherapy with haploidentical natural killer cells and Anti-GD2
      monoclonal antibody m3F8 for resistant neuroblastoma: Results of a phase I study.
AB  - Natural killer (NK) cell-mediated antibody-dependent toxicity is a potent
      mechanism of action of the anti-GD2 murine monoclonal antibody 3F8 (m3F8). Killer
      immunoglobulin-like receptor (KIR) and HLA genotypes modulate NK activity and are
      key prognostic markers in m3F8-treated patients with neuroblastoma. Endogenous NK
      cells are suppressed in the setting of high tumor burden and chemotherapy.
      Allogeneic NK-cells however, demonstrate potent anti-neuroblastoma activity. We
      report on the results of a phase I clinical trial of haploidentical NK-cells plus
      m3F8 administered to patients with high-risk neuroblastoma after conditioning
      chemotherapy. The primary objective was to determine the maximum tolerated NK
      cell dose (MTD). Secondary objectives included assessing anti-neuroblastoma
      activity and its relationship to donor-recipient KIR/HLA genotypes, NK function,
      and donor NK chimerism. Patients received a lymphodepleting regimen prior to
      infusion of haploidentical CD3-CD56+ NK-cells, followed by m3F8. Overall and
      progression free survival (PFS) were assessed from the time of first NK-cell
      dose. Univariate Cox regression assessed relationship between dose and outcomes.
      Thirty-five patients received NK-cells at one of five dose levels ranging from
      <1*106 to 50*106 CD3-CD56+cells/kg. One patient experienced grade 3 hypertension
      and grade 4 pneumonitis. MTD was not reached. Ten patients (29%) had complete or
      partial response; 17 (47%) had no response; and eight (23%) had progressive
      disease. No relationship was found between response and KIR/HLA genotype or
      between response and FcgammaRIII receptor polymorphisms. Patients receiving
      >10*106 CD56+cells/kg had improved PFS (HR: 0.36, 95%CI: 0.15-0.87, p = 0.022).
      Patient NK-cells displayed high NKG2A expression, leading to inhibition by HLA-E
      expressing neuroblastoma cells. Adoptive NK-cell therapy in combination with m3F8
      is safe and has anti-neuroblastoma activity at higher cell doses.

PMID- 30221059
TI  - Intramuscular vaccination targeting mucosal tumor draining lymph node enhances
      integrins-mediated CD8+ T cell infiltration to control mucosal tumor growth.
AB  - Purpose: Mucosal immunization is suggested to be crucial for controlling tumors
      in the mucosal region; however, therapeutic DNA vaccination with electroporation
      in various mucosal sites has yet to become clinically adaptable. Since tumor
      draining lymph nodes (tdLNs) have been suggested as immune-educated sites that
      can be utilized to mount a potent antitumor immune response, we examined whether
      intramuscular DNA vaccination with electroporation at sites that target the
      mucosal tdLNs could elicit mucosal immune response to restrict tumor growth.
      Experimental Design: The efficacy and mechanism of intramuscular administration
      of a therapeutic DNA vaccine with electroporation at different sites was examined
      by lymphocyte analysis, tumor growth, mouse survival, as well as integrin
      expression, in mice bearing orthotopic HPV16 E6/E7+ syngeneic TC-1 tumors in
      various mucosal areas. Results: While provoking comparable systemic CD8+ T cell
      responses, intramuscular hind leg vaccination generated stronger responses in
      cervicovaginal-draining LNs to control cervicovaginal tumors, whereas
      intramuscular front leg vaccination generated stronger responses in oral-draining
      LNs to control buccal tumors. Surgical removal of tdLNs abolished the antitumor
      effects of therapeutic vaccination. Mucosal-tdLN-targeted intramuscular
      vaccination induced the expression of mucosal-homing integrins LPAM-1 and CD49a
      by tumor-specific CD8+ T cells in the tdLNs. Inhibition of these integrins
      abolished the therapeutic effects of vaccination and the infiltration of tumor
      specific CD8+ T cells into mucosal tumors. Conclusions: Our findings demonstrate
      that tumor draining lymph nodes targeted intramuscular immunization can
      effectively control mucosal tumors, which represents a readily adaptable strategy
      for treating mucosal cancers in humans.

PMID- 30221058
TI  - Lymphatic vessel density is associated with CD8+ T cell infiltration and
      immunosuppressive factors in human melanoma.
AB  - Increased density of tumor-associated lymphatic vessels correlates with poor
      patient survival in melanoma and other cancers, yet lymphatic drainage is
      essential for initiating an immune response. Here we asked whether and how
      lymphatic vessel density (LVD) correlates with immune cell infiltration in
      primary tumors and lymph nodes (LNs) from patients with cutaneous melanoma. Using
      immunohistochemistry and quantitative image analysis, we found significant
      positive correlations between LVD and CD8+ T cell infiltration as well as
      expression of the immunosuppressive molecules inducible nitric oxide synthase
      (iNOS) and 2,3-dioxygenase (IDO). Interestingly, similar associations were seen
      in tumor-free LNs adjacent to metastatic ones, indicating loco-regional effects
      of tumors. Our data suggest that lymphatic vessels play multiple roles at tumor
      sites and LNs, promoting both T cell infiltration and adaptive immunosuppressive
      mechanisms. Lymph vessel associated T cell infiltration may increase
      immunotherapy success rates provided that the treatment overcomes adaptive immune
      resistance.

PMID- 30221060
TI  - Immune effectors responsible for the elimination of hyperploid cancer cells.
AB  - The immune system avoids oncogenesis and slows down tumor progression through a
      mechanism called immunosurveillance. Nevertheless, some malignant cells manage to
      escape from immune control and form clinically detectable tumors. Tetraploidy,
      which consists in the intrinsically unstable duplication of the genome, is
      considered as a (pre)-cancerous event that can result in aneuploidy and
      contribute to oncogenesis. We previously described the fact that tetraploid cells
      can be eliminated by the immune system. Here, we investigate the role of
      different innate and acquired immune effectors by inoculating hyperploid cancer
      cells into wild type or mice bearing different immunodeficient genotypes (Cd1d-/
      , FcRn-/-, Flt3l-/-, Foxn1nu/nu, MyD88-/-, Nlrp3-/-, Ighmtm1Cgn, Rag2-/-),
      followed by the monitoring of tumor incidence, growth and final ploidy status.
      Our results suggest that multiple different immune effectors including B, NK, NKT
      and T cells, as well as innate immune responses involving the interleukine-1
      receptor and the Toll-like receptor systems participate to the immunoselection
      against hyperploid cells. Hence, optimal anticancer immunosurveillance likely
      involves the contribution of multiple arms of the immune system.

PMID- 30221062
TI  - Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in
      colorectal cancer: Relationship with sidedness and prognosis.
AB  - Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 has
      been demonstrated to confer a prognostic value in colorectal cancer (CRC), but no
      studies have investigated whether this association differs according to tumour
      location. In this study, immunohistochemical expression of PD-1 and PD-L1 was
      analysed in tissue microarrays with primary tumours from 557 incident CRC cases
      from a prospective population-based cohort. Univariable and multivariable Cox
      regression analyses, adjusted for age, sex, TNM stage, differentiation grade and
      vascular invasion, were applied to determine the impact of biomarker expression
      on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of
      right colon, left colon, and rectum. High PD-L1 expression on tumour-infiltrating
      immune cells was an independent factor of a prolonged OS in the entire cohort
      (hazard ratio [HR] = 0.49; 95% confidence interval [CI] CI 0.35 - 0.68), and in
      tumours of the right colon (HR = 0.43; 95% CI 0.25 - 0.74) and the left colon (HR
      = 0.28; 95% CI 0.13 - 0.61), but not in rectal cancer. Tumour-specific PD-L1
      expression was not prognostic, neither in the full cohort nor according to tumour
      location. High immune cell-specific PD-1 expression was associated with a
      prolonged OS in the entire cohort and in tumours of the right colon, but not in
      the left colon or rectum, and only in univariable analysis. In conclusion, these
      results demonstrate that immune cell-specific PD-L1 and PD-1 expression is
      prognostic in a site-dependent manner, whereas tumour-specific PD-L1-expression
      is not prognostic in CRC.

PMID- 30221061
TI  - OX40 triggering concomitant to IL12-engineered cell vaccine hampers the
      immunoprevention of HER2/neu-driven mammary carcinogenesis.
AB  - This study evaluated the effects of combining an OX40 agonistic antibody (aOX40)
      with a cell vaccine targeting HER2/neu, called "Triplex". Such HER2/neu cell
      vaccine included two biological adjuvants (interleukin 12 (IL12) and allogeneic
      histocompatibility antigens) and was previously found able to prevent
      autochthonous HER2/neu-driven mammary carcinogenesis. Timing of aOX40
      administration, concomitantly or after cell vaccination, gave opposite results.
      Unexpectedly, vaccine efficacy was hampered by concomitant OX40 triggering. Such
      decreased immunoprevention was likely due to a reduced induction of anti-HER2/neu
      antibodies and to a higher level of Treg activation. On the contrary, aOX40
      administration after the completion of vaccination slightly but significantly
      increased immunopreventive vaccine efficacy, and led to increased production of
      GM-CSF and IL10. In conclusion, OX40 triggering can either impair or ameliorate
      immunoprevention of HER2/neu-driven mammary carcinogenesis depending on the
      schedule of aOX40 administration.

PMID- 30221064
TI  - High-dimensional mass cytometry analysis revealed microenvironment complexity in
      chronic lymphocytic leukemia.
AB  - In this study, we extensively dissected the phenotypic complexity of the splenic
      tumor microenvironment (TME) in chronic lymphocytic leukemia (CLL) by high
      dimensional mass cytometry (CyTOF). As a result, we identified potential new
      targets and tested a dual immune checkpoint blockade targeting the TME in pre
      clinical mouse models of CLL.

PMID- 30221063
TI  - The blood mMDSC to DC ratio is a sensitive and easy to assess independent
      predictive factor for epithelial ovarian cancer survival.
AB  - Epithelial ovarian cancer (EOC) may cause abnormal blood levels of leukocytes.
      This paraneoplastic manifestation is associated with a worse response to therapy
      and shorter survival. To understand the complexity and nature of these
      leukocytes, we dissected the different populations of myeloid cells and analyzed
      their relation to clinical outcome. Therefore, baseline blood samples of 36 EOC
      patients treated either with carboplatin/doxorubucin or with gemcitabine were
      analyzed for different subsets of monocytes/macrophages, myeloid derived
      suppressor cells (MDSC) and dendritic cells (DC) using multiparameter flow
      cytometry as well as functional assays for myeloid cell mediated suppression of
      antigen-specific T cell reactivity. Healthy donor blood served as control. EOC
      patients displayed an increase in monocytes/macrophages, monocytic MDSC (mMDSC)
      and CD33-CD11b+CD14-CD15- double-negative MDSC (CD33- dnMDSC) and a decrease in
      the frequency of DC, across all EOC subtypes. A low frequency of DC and high
      frequencies of monocytes/macrophages and mMDSC, but not CD33- dnMDSC, were
      associated with poor overall survival. Patient's monocytes/macrophages and mMDSC,
      but not CD33- dnMDSC, were shown to suppress T cell reactivity in vitro. The
      mMDSC and DC frequencies were not altered upon treatment. Importantly, the mMDSC
      to DC ratio was the strongest independent, highly sensitive and specific,
      predictive factor for survival. This was irrespective of the type of chemotherapy
      or disease stage and outperformed classical parameters as WHO status or time from
      last chemotherapy. Thus, the baseline blood mMDSC to DC ratio is a robust,
      independent and easy to analyze predictive factor for EOC survival, and may
      assist patient selection for immunotherapy.

PMID- 30221065
TI  - A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune
      checkpoint.
AB  - PD-L1-blocking antibodies produce significant clinical benefit in selected cancer
      patients by reactivating functionally-impaired antigen-experienced anticancer T
      cells. However, the efficacy of current PD-L1-blocking antibodies is potentially
      reduced by 'on-target/off-tumor' binding to PD-L1 widely expressed on normal
      cells. This lack of tumor selectivity may induce a generalized activation of all
      antigen-experienced T cells which may explain the frequent occurrence of
      autoimmune-related adverse events during and after treatment. To address these
      issues, we constructed a bispecific antibody (bsAb), designated PD-L1xEGFR, to
      direct PD-L1-blockade to EGFR-expressing cancer cells and to more selectively
      reactivate anticancer T cells. Indeed, the IC50 of PD-L1xEGFR for blocking PD-L1
      on EGFR+ cancer cells was ~140 fold lower compared to that of the analogous PD-L1
      blocking bsAb PD-L1xMock with irrelevant target antigen specificity. Importantly,
      activation status, IFN-gamma production, and oncolytic activity of anti-CD3xanti
      EpCAM-redirected T cells was enhanced when cocultured with EGFR-expressing
      carcinoma cells. Similarly, the capacity of PD-L1xEGFR to promote proliferation
      and IFN-gamma production by CMVpp65-directed CD8+ effector T cells was enhanced
      when cocultured with EGFR-expressing CMVpp65-transfected cancer cells. In
      contrast, the clinically-used PD-L1-blocking antibody MEDI4736 (durvalumab)
      promoted T cell activation indiscriminate of EGFR expression on cancer cells.
      Additionally, in mice xenografted with EGFR-expressing cancer cells 111In-PD
      L1xEGFR showed a significantly higher tumor uptake compared to 111In-PD-L1xMock.
      In conclusion, PD-L1xEGFR blocks the PD-1/PD-L1 immune checkpoint in an EGFR
      directed manner, thereby promoting the selective reactivation of anticancer T
      cells. This novel targeted approach may be useful to enhance efficacy and safety
      of PD-1/PD-L1 checkpoint blockade in EGFR-overexpressing malignancies.

PMID- 30221067
TI  - PKR and GCN2 stress kinases promote an ER stress-independent eIF2alpha
      phosphorylation responsible for calreticulin exposure in melanoma cells.
AB  - The immunogenic cell death (ICD) process represents a novel therapeutic approach
      to treat tumours, in which cytotoxic compounds promote both cancer cell death and
      the emission of damage-associated molecular patterns (DAMPs) from dying cells, to
      activate the immune system against the malignancy. Therefore, we explored the
      possibility to stimulate the key molecular players with a pivotal role in the
      execution of the ICD program in melanoma cells. To this aim, we used the pro-ICD
      agents mitoxantrone and doxorubicin and found that both agents could induce cell
      death and stimulate the release/exposure of the strictly required DAMPs in
      melanoma cells: i) calreticulin (CRT) exposure on the cell membrane; ii) ATP
      secretion; iii) type I IFNs gene up-regulation and iv) HMGB1 secretion,
      highlighting no interference by oncogenic BRAF. Importantly, although the ER
      stress-related PERK activation has been linked to CRT externalization, through
      the phosphorylation of eIF2alpha, we found that this stress pathway together with
      PERK were not involved in melanoma cells. Notably, we identified PKR and GCN2 as
      key mediators of eIF2alpha phosphorylation, facilitating the translocation of CTR
      on melanoma cells surface, under pro-ICD drugs stimulation. Therefore, our data
      indicate that pro-ICD drugs are able to stimulate the production/release of DAMPs
      in melanoma cells at least in vitro, indicating in this approach a potential new
      valuable therapeutic strategy to treat human skin melanoma malignancy.

PMID- 30221068
TI  - Clinical implication of tumor mutational burden in patients with HER2-positive
      refractory metastatic breast cancer.
AB  - This study explored the clinical implications of tumor mutational burden (TMB) in
      a well-defined HER2-positive metastatic breast cancer (MBC) patient population
      who had been previously treated but had subsequent disease progression. Whole
      exome sequencing was performed on formalin-fixed paraffin-embedded tumor samples
      and matched normal tissue. Among the 46 patients, 13 (28.3%) were estrogen
      receptor-positive and nine (19.6%) were progesterone receptor-positive by
      immunohistochemistry analysis. Twenty patients (43.5%) had recurrent MBC compared
      with de novo MBC (n = 26, 56.5%). Sixteen patients (34.6%) demonstrated more than
      100 somatic non-synonymous SNV mutations, which was predefined as a high TMB. The
      median follow-up duration was 57.5 months. The median overall survival (mOS)
      differed significantly between low and high TMB status (44.9 months vs. 85.8
      months, respectively, p = 0.016). In a multivariate Cox regression analysis, TMB
      was the only independent prognostic factor for good metastatic overall survival
      after adjusting for age and recurrence (Hazard ratio [HR] = 0.32, 95% confidence
      interval [CI], 0.103-0.998, p = 0.049). These data suggest that high TMB may be a
      prognostic marker for predicting good overall survival for patients undergoing
      conventional HER2-directed treatments and chemotherapy. Further, future clinical
      trials harnessing TMB may benefit by identifying an appropriate population who
      may have a favorable response to immunotherapy after recurrence following HER2
      directed treatments.

PMID- 30221066
TI  - Personal history of infections and immunotherapy: Unexpected links and possible
      therapeutic opportunities.
AB  - The recent breakthroughs in the understanding of tumor immune biology have given
      rise to a new generation of immunotherapies, harnessing the immune system to
      eliminate tumors. As the typology and frequency of encountered infections are
      susceptible to shape the immune system, it could also impact the efficiency of
      immunotherapy. In this review, we report evidences for an indirect link between
      personal history of infection and different strategies of immunotherapy. In the
      current context of interest rise for personalized medicine, we discuss the
      potential medical applications of considering personal history of infection to
      design immunotherapeutic strategies.

PMID- 30221070
TI  - Cell-type specific MyD88 signaling is required for intestinal tumor initiation
      and progression to malignancy.
AB  - The signal adapter MyD88, an essential component of Toll-like receptor (TLR)
      signaling, is important for gut-microbiome interactions. However, its
      contribution to cancer and its cell-type specific functions are controversially
      discussed. Therefore, we generated new tissue-specific mouse models and analyzed
      the clinical importance in human colorectal cancer. A gene-trap was inserted into
      the murine Myd88 gene (Myd88LSL), yielding MyD88-deficient background with Cre
      mediated re-expression in myeloid (MYEL) or intestinal epithelial cells (IECs).
      These lines were bred with the Apc1638N model that develops invasive
      adenocarcinoma and analyzed at 12 months. Further, two patient collectives of
      colorectal cancer (n = 61, and n = 633) were analyzed for expression of Myd88 and
      TLRs. MyD88 expression was significantly increased in carcinomas, and increased
      intratumoral levels of MyD88 and TLR pathway components were associated with
      significantly shorter disease-free (P = .011), and overall survival (P < .0001).
      In accordance, fully MyD88-deficient mice showed highly significantly decreased
      tumor incidence, tumor numbers, increased survival, and, importantly, fully
      lacked malignant lesions. Thus, MyD88 is essential for tumorigenesis and
      especially progression to malignancy. Tissue-specific re-expression of MyD88
      highly significantly increased tumor initiation by differing mechanisms. In
      intestinal epithelia, MyD88 enhanced epithelial turnover, whereas in myeloid
      cells, it led to increased production of tumor- and stemness-enhancing cytokines,
      significantly associated with altered expression of adaptive immune genes.
      However, neither re-expression of MyD88 in IECs or myeloid cells was sufficient
      for malignant progression to carcinoma. Thus, MyD88 crucially contributes to
      colorectal cancer initiation and progression with non-redundant and cell-type
      specific functions, constituting an attractive therapeutic target.

PMID- 30221069
TI  - TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival
      in GBM.
AB  - The use of inhibitory checkpoint blockade in the management of glioblastoma has
      been studied in both preclinical and clinical settings. TIGIT is a novel
      checkpoint inhibitor recently discovered to play a role in cancer immunity. In
      this study, we sought to determine the effect of anti-PD-1 and anti-TIGIT
      combination therapy on survival in a murine glioblastoma (GBM) model, and to
      elucidate the underlying immune mechanisms. Using mice with intracranial GL261
      luc+ tumors, we found that TIGIT expression was upregulated on CD8+ and
      regulatory T cells (Tregs) in the brain compared to draining cervical lymph nodes
      (CLN) and spleen. We then demonstrated that treatment using anti-PD-1 and anti
      TIGIT dual therapy significantly improved survival compared to control and
      monotherapy groups. The therapeutic effect was correlated with both increased
      effector T cell function and downregulation of suppressive Tregs and tumor
      infiltrating dendritic cells (TIDCs). Clinically, TIGIT expression on tumor
      infiltrating lymphocytes was shown to be elevated in patient GBM samples,
      suggesting that the TIGIT pathway may be a valuable therapeutic target.
      Expression of the TIGIT ligand, PVR, further portended a poor survival outcome in
      patients with low-grade glioma. We conclude that anti-TIGIT is an effective
      treatment strategy against murine GBM when used in combination with anti-PD-1,
      improving overall survival via modifications of both the T cell and myeloid
      compartments. Given evidence of PVR expression on human GBM cells, TIGIT presents
      as a promising immune therapeutic target in the management of these patients.

PMID- 30221072
TI  - Pattern Electroretinogram Detects Localized Glaucoma Defects.
AB  - Purpose: We evaluated the clinical ability of pattern electroretinogram (PERG) to
      detect functional losses in the affected hemifield of open-angle glaucoma
      patients with localized perimetric defects. Methods: Hemifield (horizontally
      defined) steady-state PERGs (h-PERGs) were recorded in response to 1.7 c/deg
      alternating gratings from 32 eyes of 29 glaucomatous patients with a perimetric,
      focal one-hemifield defect, 10 eyes of 10 glaucomatous patients with a diffuse
      perimetric defect, and 18 eyes of 18 age-matched normal subjects. Standard
      automated perimetry (SAP) and spectral-domain optical coherence tomography (SD
      OCT) for retinal nerve fiber layer (RNFL) thickness also were performed. h-PERG
      amplitudes and ratios, calculated corresponding hemifield perimetric deviations,
      as well as hemiretina RNFL thicknesses were analyzed. Results: h-PERG amplitudes,
      perimetric deviations, and RNFL thicknesses showed losses (P < 0.001) when
      comparing affected with unaffected hemifields of localized glaucomatous eyes. No
      differences were found in h-PERG amplitudes between hemifields of normal or
      diffuse glaucomatous eyes. h-PERG amplitude ratios (affected/unaffected
      hemifield) in localized glaucoma were lower (P < 0.001) than the ratios from
      normal or diffuse glaucomatous eyes. The areas under the receiver operating
      characteristic curves for h-PERG amplitude ratios, comparing localized-defect
      glaucomatous eyes with normal or diffuse glaucomatous eyes, were 0.93 and 0.91,
      respectively. Conclusions: h-PERG assessment showed good diagnostic accuracy to
      confirm localized glaucomatous defects detected perimetrically. This test may be
      particularly useful in cognitively impaired patients or young/nonverbal patients
      unable to provide reliable visual fields. Translational Relevance: h-PERG
      provides a sensitive objective measure to confirm focal losses detected with SAP
      and/or RNFL thickness analysis.

PMID- 30221071
TI  - Gene expression profiling and immune cell-type deconvolution highlight robust
      disease progression and survival markers in multiple cohorts of CTCL patients.
AB  - CTCL follows different courses depending on the clinical stage at the time of
      diagnosis. Patients with early stage Mycosis Fungoides (MF) variant of CTCL may
      experience an indolent course over decades, whereas patients with advanced MF and
      Sezary Syndrome (SS) disease at diagnosis, often succumb within 5 years. Even
      within early stage CTCL/MF, a minority of patients will progress to more advanced
      stages. We recently generated RNA sequencing data on 284 CTCL-relevant genes for
      157 patients and identified differentially expressed genes across stages I-IV. In
      this study, we aim to validate robust molecular markers linked to disease
      progression and survival. We performed multiple hypothesis testing-corrected
      analysis of variance (ANOVA) on the expression of individual genes across all
      CTCL samples and early stage (<=IIA) CTCL/MF patients. We used in silico immune
      cell-type deconvolution from gene expression data to estimate immune cell
      populations. Based on the analysis of all CTCL samples, we identified TOX, FYB,
      and CD52 as predictors of disease progression and poor survival. Among early
      stage (<=IIA) CTCL/MF patients, these 3 genes, along with CCR4, were valuable to
      predict disease progression. We validated these 4 genes in 3 independent,
      external Sezary Syndrome patient cohorts with RNA-Sequencing data. In silico
      immune cell-type deconvolution revealed that neutrophil infiltration in early
      stage MF conveyed a higher risk for disease progression. Also, NK cell
      infiltration in late stage MF/SS correlated with improved survival. TOX, FYB,
      CCR4 and CD52 are robust disease progression and decreased survival biomarkers in
      CTCL.

PMID- 30221073
TI  - Motility Changes and Diplopia After Baerveldt Glaucoma Drainage Device
      Implantation or After Trabeculectomy.
AB  - Purpose: The purpose of this study was to quantify any diplopia and motility
      changes after the implantation of a Baerveldt glaucoma implant (BGI) or after
      trabeculectomy (TE). Methods: We analyzed 51 patients with a BGI and 52 patients
      with a TE from a prospective cohort study. To quantify any diplopia, we asked
      patients about the presence of diplopia at 1 year after surgery. To quantify any
      ocular motility changes, we measured ductions in eight gaze directions, the
      patients' ocular alignment and their fusion range before and 1 year after
      surgery. Results: In the BGI group, 14 patients (28%) experienced diplopia
      compared with one patient (2%) in the TE group (P < 0.001). Duction changes were
      more commonly observed in the BGI group (35%) than in the TE group (19%). In the
      BGI group, ductions were mostly restricted in elevation (13%; P < 0.001), in
      abduction (13%), in elevation in 25 degrees  adduction (13%; P = 0.044), and in
      elevation in 25 degrees  abduction (25%; P < 0.001). In 32% of the patients,
      their near horizontal ocular alignment shifted, notably in exodirection (P =
      0.04). The fusion range decreased significantly in the horizontal direction (
      12.6 degrees  +/- 10.3 degrees , mean +/- standard deviation; P = 0.01).
      Conclusions: BGI surgery was significantly associated with postoperative diplopia
      and impaired eye motility (reduced ductions), mostly present in abduction,
      elevation, elevation in 25 degrees  adduction, and elevation in 25 degrees 
      abduction. Even without impaired ductions, diplopia could come about.
      Translational Relevance: By studying diplopia across glaucoma patients
      prospectively with diplopia questionnaires and extensive orthoptic measurements,
      we gain better insight into its occurrence.

PMID- 30221074
TI  - Parenting, the other oldest profession in the world - a cross-sectional study of
      parenting and child outcomes in South Africa and Malawi.
AB  - Background: Parenting quality is important in child development. In the presence
      of HIV poverty and life stress, parenting may be challenged and child development
      affected. Methods: This study examines cross-sectional associations of
      situational factors such as poverty, mental health, HIV status, living with a
      biological parent, and stigma with good parenting and child outcomes (n=989;
      age=4-13 years) within the Child Community Care study (South Africa and Malawi).
      A parenting measure was created from 10 variables comprising 6 child and 4 parent
      ratings. These were highly correlated. Total parenting score was generated on a
      10 point continuous scale, with a good parenting cut off then defined as >=8 out
      of a possible 10. Results: Five factors were associated with good parenting.
      Positively associated with good parenting were being the biological parent of the
      child, parental mental health and dwelling in households with multiple adults.
      Poverty and stigma were negatively associated with good parenting. Using multiple
      mediation analysis, a positive direct effect of good parenting was found on child
      self-esteem, child behaviour and educational risks with a partial mediation via
      child depression and trauma. Conclusions: These data highlight possible
      intervention points. Influences on parenting could be seen through being the
      biological parent, parental mental health, poverty and stigma. In these
      challenging environments, health, nutrition, mental health, education, and
      treatment to keep parents alive are all clearly identified as potential pathways
      to ensure child well-being.

PMID- 30221075
TI  - The Epidemiology of Slipped Capital Femoral Epiphysis in American Samoa.
AB  - The Maori of New Zealand have been identified as a high-risk population for
      slipped capital femoral epiphysis (SCFE). This study assessed whether the burden
      of disease from SCFE in the American Territory of American Samoa is similar to
      that identified in the Maori. This was a retrospective review of children from
      American Samoa treated for SCFE at a tertiary care pediatric hospital between
      2005-2014. Demographic, clinical, and radiographic information was collected. All
      patients were followed for at least one year after surgery and prophylactically
      pinned hips were not included. Data for determining incidence was obtained from
      the United States Census Bureau. Between 2005-2014, 55 American Samoan youth were
      treated for 73 SCFE. The incidence in the "at-risk" population 5-14 years of age
      was 53.1 per 100,000. Patients had a mean BMI of 29.5 (19.4-46.4) and mean weight
      of 76.7 kg (45.9-139 kg). Southwick angle was a mean 40.6 degrees +/- 20.4
      degrees  (6-83 degrees ). Overall, 82.2% of hips were treated with in-situ
      cannulated screw fixation. At a minimum one-year after initial surgery, 22 hips
      (30.1%) required major surgery including intertrochanteric osteotomy,
      osteochondroplasty, or total hip replacement. The incidence of SCFE in American
      Samoa is extremely high, 53.1 per 100,000 of "at-risk" population 5-14 years old.
      The mean weight and BMI in SCFE patients from American Samoa is substantially
      higher than previously published reports. Furthermore, morbidity from SCFE in
      this population is substantial with 30.1% requiring major surgery either at the
      time of physeal stabilization or in subsequent years.

PMID- 30221076
TI  - Assessment, Education, and Access: Kona Hawai'i WIC Oral Health Pilot Project.
AB  - The Kona WIC oral health pilot project was developed to assess the oral health
      beliefs and behaviors of parents of children and pregnant women at the Kona WIC
      site and to demonstrate the ease of providing oral health education to families
      in order to improve oral health behaviors. Data were collected from 50 families
      about the oral health behaviors and dental care of a total of 73 children,
      including 5 pregnant women, four of whom had a child enrolled in WIC and one
      pregnant woman without any previous children. Data revealed that 68% of children
      with teeth had been seen by a dentist within 6 to 12 months of the study visit.
      Mothers were seen less often, with 55% stating that they had not been seen for a
      dental visit for over one year. Parental knowledge about the effects of fluoride
      on teeth was limited; however, 90% of the parents would allow fluoride varnish
      applied to their child's teeth, 88% would give daily fluoride drops/tablets to
      their child, and 78% would support water fluoridation if it would help to improve
      their children's oral health. Additionally, for children old enough to receive
      fluoride supplementation, 60% were not given a prescription by their health care
      providers, and 58% had not received any fluoride varnish applications. By
      offering oral health education in a WIC clinic and assisting clients to seek out
      comprehensive care within a dental home, children and caregivers can be provided
      essential education and resources early in a child's life or women's pregnancies
      to reduce poor oral health outcomes.

PMID- 30221078
TI  - Medical School Hotline: The Many Ways Physicians Care for Patients.

PMID- 30221077
TI  - Are Rapid Influenza Antigen Tests Still Clinically Useful in Today's Molecular
      Diagnostics World?
AB  - Influenza virus infection and disease historically contribute to widespread cases
      of seasonal morbidity and in some cases mortality. Prompt and accurate diagnosis
      is crucial for optimal patient management. Rapid influenza direct antigen testing
      (RIDT) offers a faster turn-around-time for results but test performance (ie,
      sensitivity and specificity) varies widely. Nucleic acid amplification testing
      (NAAT) can offer a viable alternative. The objective of this retrospective study
      was to compare the test performance of RIDT with NAAT. RIDT testing included the
      Directigen EZ Flu A+B or the Veritor System for Rapid Detection of Flu A+B. NAAT
      employed the SimplexaTM Flu A/BTM RSV assay. A total of 5,795 specimens collected
      from October to March for the 2012/2013 (n=953), 2013/2014 (n=2060) and 2014/2015
      (n=2783) seasons were co-tested by RIDT and NAAT. Using NAAT as the gold
      standard, RIDT tests had a sensitivity range of 0 to 15.7% and a specificity of
      98.2 to 100% for influenza type A. For influenza type B, RIDT tests had a
      sensitivity of 0 to 33.3% and a specificity of 98.9 to 100%. These findings
      suggest that RIDT has unacceptably low sensitivity for both influenza A and
      influenza B, despite high specificity. The key advantage of RIDT in previous
      years (faster turnaround time) has been challenged by newer NAAT technology that
      provides results in a turn-around-time comparable to RIDT, but with superior test
      performance.

PMID- 30221079
TI  - Insights in Public Health: An Island-Wide Community Food Assessment in Lana'i,
      Hawai'i: A High School Student-Centered Project.
AB  - Lana'i is a geographically isolated Hawaiian island of approximately 3,100
      residents. During the 2017-2018 school year, 22 Lana'i High and Elementary School
      juniors and seniors engaged with community members, kupuna (elders, those who
      stand at the source), stakeholders, and expert consultants to conduct an island
      wide Community Food Assessment (CFA). A CFA can provide a community comprehensive
      information about their food systems. Particular attention was given to
      indigenous, Native Hawaiian food culture and needs. Students collected 656
      surveys from a population of about 2,200 adults. Students also completed 14
      separate focus groups, interviewing a total of 43 adults in the Lana'i community.
      This high school student-driven project was the product of many years of
      engagement and preparation, generosity from community members and content
      experts, and fortunate circumstances. This paper (1) describes the history of the
      project, providing useful details around the process of building capacity,
      leveraging connections, and engaging high school students and community members
      around a critical health issue in this rural community; and (2) highlights key
      findings that will be useful for policy development and advocacy.

PMID- 30221082
TI  - General Factors of Psychopathology, Personality, and Personality Disorder: Across
      Domain Comparisons.
AB  - Three separate and distinct literatures exist investigating general factors of
      psychopathology (p factor), personality (GFP), and personality disorder (g-PD).
      Surprisingly, there has been little-to-no investigation regarding the convergence
      of these three distinct general factors. In the present investigation, two
      studies were conducted examining the convergence of the p factor, GFP, and g-PD.
      In Study 1, a combined model extracting all three factors from self-report data
      simultaneously found high convergence. The findings for the g-PD and GFP were
      replicated in Study 2 using multi-method data, wherein the GFP and the g-PD were
      extracted from a community sample of 1,630 older adults and correlated with an
      index of maladaptivity. The present findings support the position that general
      factors of psychopathology, personality disorder, and personality are likely to
      entail a common individual differences continuum, which may impact on how these
      general factors are to be understood.

PMID- 30221081
TI  - AspEm: Embedding Learning by Aspects in Heterogeneous Information Networks.
AB  - Heterogeneous information networks (HINs) are ubiquitous in real-world
      applications. Due to the heterogeneity in HINs, the typed edges may not fully
      align with each other. In order to capture the semantic subtlety, we propose the
      concept of aspects with each aspect being a unit representing one underlying
      semantic facet. Meanwhile, network embedding has emerged as a powerful method for
      learning network representation, where the learned embedding can be used as
      features in various downstream applications. Therefore, we are motivated to
      propose a novel embedding learning framework-ASPEM-to preserve the semantic
      information in HINs based on multiple aspects. Instead of preserving information
      of the network in one semantic space, ASPEM encapsulates information regarding
      each aspect individually. In order to select aspects for embedding purpose, we
      further devise a solution for ASPEM based on dataset-wide statistics. To
      corroborate the efficacy of ASPEM, we conducted experiments on two real-words
      datasets with two types of applications-classification and link prediction.
      Experiment results demonstrate that ASPEM can outperform baseline network
      embedding learning methods by considering multiple aspects, where the aspects can
      be selected from the given HIN in an unsupervised manner.

PMID- 30221083
TI  - Does getting stigma under the skin make it thinner? Emotion regulation as a
      stress-contingent mediator of stigma and mental health.
AB  - Emotion regulation deficits may link stigma to poor mental health, yet existing
      studies rely on self-reported stigma and do not consider contextual factors. In
      the present research, we examined associations among cultural stigma (i.e.,
      objective devaluation of others' status), emotion regulation deficits, and poor
      mental health. In Study 1, we created an index of cultural stigma by asking
      members of the general public and stigma experts to indicate desired social
      distance towards 93 stigmatized attributes. In Study 2, emotion regulation
      deficits mediated the association between cultural stigma and adverse mental
      health outcomes, including depressive symptoms and alcohol use problems, among
      individuals endorsing diverse stigmatized identities. The indirect effect of
      cultural stigma, via emotion regulation, on these outcomes was stronger among
      those reporting more life stress. These findings highlight the adverse impact of
      cultural stigma on mental health and its role in potentiating stigmatized
      individuals' susceptibility to general life stress.

PMID- 30221086
TI  - Effects of environmental and anthropogenic landscape features on mule deer
      harvest in Nebraska.
AB  - Understanding the habitat use of wildlife species is important for effective
      management. Nebraska has a variety of habitat types, with the majority being
      covered by rangeland and cropland. These habitat types likely influence the
      harvest of mule deer (MD; Odocoileus hemionus) in Nebraska, but their specific
      effects are unknown, and moreover, harvest may also be influenced by the
      accessibility of deer habitats for hunters. We modeled which environmental and
      anthropogenic landscape features influenced harvest densities. Spatial analysis
      in a Geographic Information System was used to determine the mean values of
      environmental and anthropogenic landscape features at the county level. We then
      used a generalized linear model to determine which of those factors influenced MD
      harvest from 2014-2016. We found that NDVI amplitude, hunter effort, road
      density, terrain roughness, and canopy cover influence MD harvest in Nebraska.
      According to our model, MD harvest densities are significantly greater areas with
      NDVI amplitude ~38, increasing hunter effort, road densities near 1,750 m/km2,
      increasing terrain roughness, and decreasing canopy cover. Understanding
      increased harvest densities of MD can be beneficial for wildlife managers,
      allowing for more efficient allocation of efforts and expenses by managers for
      population management.

PMID- 30221085
TI  - A comparison of perceptions of nuts between the general public, dietitians,
      general practitioners, and nurses.
AB  - Background: Nut consumption at the population level remains low despite the well
      documented benefits of their consumption, including their cardioprotective
      effects. Studies have suggested that advice from health professionals may be a
      means to increase nut consumption levels. Understanding how nuts are perceived by
      the public and health professionals, along with understanding the public's
      perceptions of motivators of and deterrents to consuming nuts, may inform the
      development of initiatives to improve on these low levels of consumption. The aim
      of this cross-sectional study was to compare perceptions of nuts among three
      groups of health professionals (dietitians, general practioners, and practice
      nurses) and the general public in New Zealand (NZ), along with motivators of and
      deterrents to consuming nuts amongst the general public and their experiences of
      receiving advice around nut consumption. Methods: The NZ electoral roll was used
      to identify dietitians, general practitioners (GPs), and practice nurses, based
      on their free-text occupation descriptions, who were then invited to complete a
      questionnaire with 318, 292, and 149 respondents respectively. 1,600 members of
      the general public were randomly selected from the roll with 710 respondents.
      Analyses were performed using chi-squared tests to look at differences in
      categorical variables and linear regression for differences in other variables
      between the four survey groups. Results: Although there were significant
      differences between the four groups regarding the perceptions of nuts, in general
      there was agreement that nuts are healthy, high in protein and fat, are filling,
      and some nuts are high in selenium. We noted frequent agreement that the general
      public participants would consume more if nuts: improved health (67%), were more
      affordable (60%), or improved the nutrient content (59%) and balance of fats
      (58%) within their diets. Over half the respondents reported they would eat more
      nuts if they were advised to do so by a dietitian or doctor, despite less than 4%
      reporting they had received such advice. The most frequently selected deterrents
      to increasing nut consumption were: cost (67%), potential weight gain (66%), and
      leading to eating too much fat (63%). Discussion: It is concerning that so few
      among the general public report receiving advice to consume more nuts from health
      professionals, especially given their apparent responsiveness to such advice.
      Health professionals could exploit the motivators of nut consumption, while also
      addressing the deterrents, to promote nut intake. These factors should also be
      addressed in public health messages to encourage regular nut consumption among
      the public. Educational initiatives could also be used to improve the nutritional
      knowledge of GPs and practice nurses with regard to nuts, although even
      dietitians were unsure of their knowledge in some cases.

PMID- 30221084
TI  - A novel experimental design for the measurement of metacarpal bone loading and
      deformation and fingertip force.
AB  - Background: Musculoskeletal and finite element modelling are often used to
      predict joint loading and bone strength within the human hand, but there is a
      lack of in vitro evidence of the force and strain experienced by hand bones.
      Methods: This study presents a novel experimental setup that allows the
      positioning of a cadaveric digit in a variety of postures with the measurement of
      force and strain experienced by the third metacarpal. The setup allows for the
      measurement of fingertip force as well. We tested this experimental setup using
      three cadaveric human third digits in which the flexor tendons were loaded in two
      tendon pathways: (1) parallel to the metacarpal bone shaft, with bowstringing;
      (2) a semi-physiological condition in which the tendons were positioned closer to
      the bone shaft. Results: There is substantial variation in metacarpal net force,
      metacarpal strain and fingertip force between the two tendon pathways. The net
      force acting on the metacarpal bone is oriented palmarly in the parallel tendon
      condition, causing tension along the dorsum of the metacarpal shaft, while the
      force increases and is oriented dorsally in the semi-physiological condition,
      causing compression of the dorsal metacarpal shaft. Fingertip force is also
      greater in the semi-physiological condition, implying a more efficient grip
      function. Inter-individual variation is observed in the radioulnar orientation of
      the force experienced by the metacarpal bone, the fingertip force, and the strain
      patterns on the metacarpal shaft. Conclusion: This study demonstrates a new
      method for measuring force and strain experienced by the metacarpal, and
      fingertip force in cadaveric digits that can, in turn, inform computation models.
      Inter-individual variation in loads experienced by the third digit suggest that
      there are differences in joint contact and/or internal bone structure across
      individuals that are important to consider in clinical and evolutionary contexts.

PMID- 30221087
TI  - Association of burnout with doctor-patient relationship and common stressors
      among postgraduate trainees and house officers in Lahore-a cross-sectional study.
AB  - Introduction: Burnout is defined as a prolonged state of physical and
      psychological exhaustion. Doctors, due to the demanding nature of their job, are
      susceptible to facing burnout, which has far reaching implications on their
      productivity and motivation. It affects the quality of care they provide to
      patients, thus eroding the doctor-patient relationship which embodies patient
      centeredness and autonomy. The study aims at addressing the stressors leading to
      burnout and its effect on the doctor-patient relationship. Methods: A
      descriptive, cross-sectional study design with convenience (non-probability)
      sampling technique was employed in six major hospitals of Lahore, Pakistan. A
      total of 600 doctors were approached for the study which included house officers
      or "HOs" (recent graduates doing their 1 year long internship) and post-graduate
      trainees or "PGRs" (residents for 4-5 years in their specialties). Burnout was
      measured using the Copenhagen Burnout Inventor (CBI) while attitudes towards the
      doctor-patient relationship was measured using the Patient Practitioner
      Orientation Scale (PPOS), which measures two components of the relationship:
      power sharing and patient caring. Pearson correlation and linear regression
      analysis were used to analyze the data via SPSS v.21. Results: A total of 515
      doctors consented to take part in the study (response rate 85.83%). The final
      sample consisted of 487 doctors. The burnout score was not associated with the
      total and caring domain scores of PPOS (P > 0.05). However, it was associated
      with the power sharing sub-scale of PPOS. Multiple linear regression analysis
      yielded a significant model, by virtue of which CBI scores were positively
      associated with factors such as female gender, feeling of burn out, scoring high
      on sharing domain of PPOS and a lack of personal control while CBI scores were
      negatively associated with private medical college education, having a
      significant other, accommodation away from home and a sense of never ending
      competition. Burnout levels varied significantly between house officers and post
      graduate trainees. Twenty-three percent of the participants (mostly house
      officers) had high/very high burnout levels on the CBI (Kristenson's burnout
      scoring). Both groups showed significant differences with respect to working
      hours, smoking status and income. Conclusion: Although burnout showed no
      significant association with total and caring domain scores of PPOS (scale used
      to assess doctor-patient relationship), it showed a significant association with
      the power sharing domain of PPOS suggesting some impact on the overall delivery
      of patient care. Thus, it necessitates the monitoring of stressors in order to
      provide an atmosphere where patient autonomy can be practiced.

PMID- 30221088
TI  - Growth under cold conditions in a wide perennial ryegrass panel is under tight
      physiological control.
AB  - Background: Perennial ryegrass is a cool-season grass species from the family
      Poaceae and is widely cultivated in temperate regions because it exhibits rapid
      growth and establishment, and possesses high forage quality. The extension of the
      growing season in Ireland in spring and autumn is a breeding target to make
      farming more profitable since a grass-fed diet based on grazing is the cheapest
      way of nutrition for ruminants. Methods: Fifty-seven perennial ryegrass
      accessions were screened for their ability to grow under typical Irish spring
      conditions as taken from long term temperature records in controlled climate
      chambers. They were grown in low temperature (8  degrees C/2  degrees C
      day/night) and control conditions (15  degrees C/8  degrees C day/night) in three
      consecutive independent experiments. Fresh weight, height, chlorophyll content
      and electrolyte leakage were measured, and these parameters were used to rank
      plant performance under low temperature growth conditions. Results: The results
      showed that height, yield and electrolyte leakage are excellent measures for the
      impact of cold stress tolerance. Little variation in growth was seen under cold
      stress, but a wide variety of responses were observed under control conditions.
      Discussion: Our results suggest that cold stress is under tight physiological
      control. Interestingly, the various genotypes responded differentially to more
      amenable control conditions, indicating that a quick response to more amenable
      growth conditions is a better target for breeding programmes.

PMID- 30221089
TI  - Effects of resveratrol, exercises and their combination on Farnesoid X receptor,
      Liver X receptor and Sirtuin 1 gene expression and apoptosis in the liver of
      elderly rats with nonalcoholic fatty liver.
AB  - Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic
      liver disorder. This study aims to consider effects of resveratrol, exercise and
      their combination on Farnesoid X receptor (Fxr), the liver X receptor (Lxr) and
      Sirtuin 1 (Sirt 1) genes expression in the liver of elderly rats with NAFLD.
      Methods: Rats with NAFLD were randomly divided into seven groups including
      patient, saline, resveratrol (RSV), interval exercise, continuous exercise,
      interval exercise + RSV and continuous exercise + RSV. Levels of alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase
      (ALP) in the liver tissue were measured using specific ELISA kits. A TUNEL assay
      kit was used for the assessment of hepatic cells apoptosis. Lipid profiles were
      considered by measuring the serum triglyceride, cholesterol, LDL, and HDL.
      Expression of Sirt1, Lxr and Fxr genes was considered using RT-PCR. Results:
      Resveratrol administration alone or combined with exercise training significantly
      improved the expression of Sirt1, Lxr and Fxr genes (p < 0.05) in the hepatic
      tissue of rats with NAFLD, while levels of AST, ALT, ALP enzymes, as well as
      apoptotic cells were significantly decreased (p < 0.05). Discussion: Although
      resveratrol alone improves the expression of Sirt1, Lxr and Fxr, as well as liver
      function, combined therapy with exercise training is more effective to improve
      NAFLD.

PMID- 30221090
TI  - DNA mismatch repair and CD133-marked cancer stem cells in colorectal carcinoma.
AB  - Background: Except for a few studies with contradictory observations, information
      is lacking on the possibility of association between DNA mismatch repair (MMR)
      status and the presence of cancer stem cells in colorectal carcinoma (CRC), two
      important aspects in colorectal carcinogenesis. Methods: Eighty (40 right-sided
      and 40 left-sided) formalin-fixed, paraffin-embedded primary CRC were
      immunohistochemically studied for CD133, a putative CRC stem cell marker, and MMR
      proteins MLH1, MSH2, MSH6 and PMS2. CD133 expression was semi-quantitated for
      proportion of tumor immunopositivity on a scale of 0-5 and staining intensity on
      a scale of 0-3 with a final score (units) being the product of proportion and
      intensity of tumor staining. The tumor was considered immunopositive only when
      the tumor demonstrated moderate to strong intensity of CD133 staining (a decision
      made after analysis of CD133 expression in normal colon). Deficient MMR (dMMR)
      was interpreted as unequivocal loss of tumor nuclear staining for any MMR protein
      despite immunoreactivity in the internal positive controls. Results: CD133 was
      expressed in 36 (90.0%) left-sided and 28 (70.0%) right-sided tumors (p < 0.05)
      and CD133 score was significantly higher in left- (mean +/- SD = 9.6 +/- 5.3
      units) compared with right-sided tumors (mean +/- SD = 6.8 +/- 5.6 units) p <
      0.05). dMMR was noted in 14 (35%) right-sided and no (0%) left-sided CRC. When
      stratified according to MMR status, dMMR cases showed a lower frequency of CD133
      expression (42.9%) and CD133 score (mean +/- SD = 2.5 +/- 3.6 units) compared
      with pMMR tumors on the right (frequency = 84.6%; mean score +/- SD = 9.2 +/- 5.0
      units) as well as pMMR tumors on the left (frequency = 90.0%; mean score +/- SD =
      9.6 +/- 5.3 units) (p < 0.05). Interestingly, frequencies of CD133
      immunoreactivity and CD133 scores did not differ between pMMR CRC on the right
      versus the left (p > 0.05). Conclusion: Proficient MMR correlated with high
      levels of CD133-marked putative cancer stem cells in both right- and left-sided
      tumors, whereas significantly lower levels of CD133-marked putative cancer stem
      cells were associated with deficient MMR status in colorectal carcinomas found on
      the right.

PMID- 30221091
TI  - A short, robust brain activation control task optimised for pharmacological fMRI
      studies.
AB  - Background: Functional magnetic resonance imaging (fMRI) is a popular method for
      examining pharmacological effects on the brain; however, the BOLD response is
      dependent on intact neurovascular coupling, and potentially modulated by a number
      of physiological factors. Pharmacological fMRI is therefore vulnerable to
      confounding effects of pharmacological probes on general physiology or
      neurovascular coupling. Controlling for such non-specific effects in
      pharmacological fMRI studies is therefore an important consideration, and there
      is an additional need for well-validated fMRI task paradigms that could be used
      to control for such effects, or for general testing purposes. Methods: We have
      developed two variants of a standardized control task that are short (5 minutes
      duration) simple (for both the subject and experimenter), widely applicable, and
      yield a number of readouts in a spatially diverse set of brain networks. The
      tasks consist of four functionally discrete three-second trial types (plus
      additional null trials) and contain visual, auditory, motor and cognitive (eye
      movements, and working memory tasks in the two task variants) stimuli.
      Performance of the tasks was assessed in a group of 15 subjects scanned on two
      separate occasions, with test-retest reliability explicitly assessed using intra
      class correlation coefficients. Results: Both tasks produced robust patterns of
      brain activation in the expected brain regions, and region of interest-derived
      reliability coefficients for the tasks were generally high, with four out of
      eight task conditions rated as 'excellent' or 'good', and only one out of eight
      rated as 'poor'. Median values in the voxel-wise reliability measures were also
      >0.7 for all task conditions, and therefore classed as 'excellent' or 'good'. The
      spatial concordance between the most highly activated voxels and those with the
      highest reliability coefficients was greater for the sensory (auditory, visual)
      conditions than the other (motor, cognitive) conditions. Discussion: Either of
      the two task variants would be suitable for use as a control task in future
      pharmacological fMRI studies or for any other investigation where a short,
      reliable, basic task paradigm is required. Stimulus code is available online for
      re-use by the scientific community.

PMID- 30221092
TI  - Tibia functionality and Division II female and male collegiate athletes from
      multiple sports.
AB  - Background: Bone strength is developed through a combination of the size and
      shape (architecture) of a bone as well as the bone's material properties; and
      therefore, no one outcome variable can measure a positive or negative adaptation
      in bone. Skeletal robusticity (total area/ bone length) a measure of bones
      external size varies within the population and is independent of body size, but
      robusticity has been associated with bone strength. Athletes may have similar
      variability in robusticity values as the general population and thus have a wide
      range of bone strengths based on the robustness of their bones. Therefore, the
      purpose of this study was to determine if an athlete's bone strength and cortical
      area relative to body size was dependent on robusticity. The second aim was to
      determine if anthropometry or muscle function measurements were associated with
      bone robusticity. Methods: Bone variables contributing to bone strength were
      measured in collegiate athletes and a reference group using peripheral
      quantitative computed tomography (pQCT) at the 50% tibial site. Bone
      functionality was assessed by plotting bone strength and cortical area vs body
      size (body weight x tibial length) and robustness (total area/length) vs body
      size. Bone strength was measured using the polar strength-strain index (SSIp).
      Based on the residuals from the regression, an athlete's individual functionality
      was determined, and two groups were formed "weaker for size" (WS) and "stronger
      for size" (SS). Grip strength, leg extensor strength and lower body power were
      also measured. Results: Division II athletes exhibited a natural variation in
      (SSIp) relative to robusticity consistent with previous studies. Bone strength
      (SSIp) was dependent on the robusticity of the tibia. The bone traits that
      comprise bone strength (SSIp) were significantly different between the SS and WS
      groups, yet there were minimal differences in the anthropometric data and muscle
      function measures between groups. A lower percentage of athletes from ball sports
      were "weaker for size" (WS group) and a higher percentage of swimmers were in the
      WS group. Discussion: A range of strength values based on robusticity occurs in
      athletes similar to general populations. Bones with lower robusticity (slender)
      were constructed with less bone tissue and had less strength. The athletes with
      slender bones were from all sports including track and field and ball sports but
      the majority were swimmers. Conclusions: Athletes, even after optimal training
      for their sport, may have weaker bones based on robusticity. Slender bones may
      therefore be at a higher risk for fracture under extreme loading events but also
      yield benefits to some athletes (swimmers) due to their lower bone mass.

PMID- 30221093
TI  - Data challenges of biomedical researchers in the age of omics.
AB  - Background: High-throughput technologies are rapidly generating large amounts of
      diverse omics data. Although this offers a great opportunity, it also poses great
      challenges as data analysis becomes more complex. The purpose of this study was
      to identify the main challenges researchers face in analyzing data, and how
      academic libraries can support them in this endeavor. Methods: A multimodal needs
      assessment analysis combined an online survey sent to 860 Yale-affiliated
      researchers (176 responded) and 15 in-depth one-on-one semi-structured
      interviews. Interviews were recorded, transcribed, and analyzed using NVivo 10
      software according to the thematic analysis approach. Results: The survey
      response rate was 20%. Most respondents (78%) identified lack of adequate data
      analysis training (e.g., R, Python) as a main challenge, in addition to not
      having the proper database or software (54%) to expedite analysis. Two main
      themes emerged from the interviews: personnel and training needs. Researchers
      feel they could improve data analyses practices by having better access to the
      appropriate bioinformatics expertise, and/or training in data analyses tools.
      They also reported lack of time to acquire expertise in using bioinformatics
      tools and poor understanding of the resources available to facilitate analysis.
      Conclusions: The main challenges identified by our study are: lack of adequate
      training for data analysis (including need to learn scripting language), need for
      more personnel at the University to provide data analysis and training, and
      inadequate communication between bioinformaticians and researchers. The authors
      identified the positive impact of medical and/or science libraries by
      establishing bioinformatics support to researchers.

PMID- 30221094
TI  - Complete paternally inherited mitogenomes of two freshwater mussels Unio pictorum
      and Sinanodonta woodiana (Bivalvia: Unionidae).
AB  - Freshwater bivalves from the family Unionidae usually have two very divergent
      mitogenomes, inherited according to the doubly uniparental model. The early
      divergence of these two mitogenomic lineages gives a unique opportunity to use
      two mitogenomic data sets in a single phylogenetic context. However, the number
      of complete sequences of the maternally inherited mitogenomes of these animals
      available in GenBank greatly exceeds that of the paternally inherited
      mitogenomes. This is a problem for phylogenetic reconstruction because it limits
      the use of both mitogenomic data sets. Moreover, since long branch attraction
      phenomenon can bias reconstructions if only a few but highly divergent taxa are
      considered, the shortage of the faster evolving paternally inherited mitogenome
      sequences is a real problem. Here we provide, for the first time, complete
      sequences of the M mitogenomes sampled from Polish populations of two species:
      native Unio pictorum and invasive Sinanodonta woodiana. It increases the
      available set of mitogenomic pairs to 18 species per family, and allows
      unambiguous reconstruction of phylogenetic relationships among them. The
      reconstructions based on M and F mitogenomes which were separated for many
      millions of years, and subject to differing evolutionary dynamics, are fully
      congruent.

PMID- 30221095
TI  - Techno-Economic Assessment, Scalability, and Applications of Aerosol Lignin Micro
      and Nanoparticles.
AB  - Lignin micro- and nanoparticles (LMNPs) synthesized from side-streams of pulp and
      paper and biorefinery operations have been proposed for the generation of new,
      high-value materials. As sustainable alternatives to particles of synthetic or
      mineral origins, LMNPs viability depends on scale-up, manufacturing cost, and
      applications. By using experimental data as primary source of information, along
      with industrial know-how, we analyze dry and spherical LMNPs obtained by our
      recently reported aerosol/atomization method. First, a preliminary evaluation
      toward the commercial production of LMNPs from industrial lignin precursors is
      presented. Following, we introduce potential LMNPs applications from a financial
      perspective. Mass and energy balances, operating costs, and capital investment
      are estimated and discussed in view of LMNPs scalability prospects. The main
      potential market segments identified (from a financial perspective) include
      composite nanofillers, solid foams, emulsion stabilizers, chelating agents, and
      UV protection. Our technical, financial, and market assessment represent the
      basis for R&D planning and efforts to lower the risk related to expected
      industrialization efforts. Manufacturing costs were estimated between 870 and
      1170 USD/t; also, minimum selling prices varied from 1240 and 1560 USD/t,
      depending on raw materials used. Sensitivity analysis indicated that
      manufacturing cost can be as low as 600 USD/t, depending on the process
      conditions considered. Finally, based on the financial assessment, potential
      applications were identified.

PMID- 30221096
TI  - CyberKnife(r) Radiosurgery as First-line Treatment for Catastrophic Epilepsy
      Caused by Hypothalamic Hamartoma.
AB  - Hypothalamic hamartomas (HH) are deep-seated lesions often associated with
      catastrophic epilepsy (an epileptic syndrome characterized by severe, drug
      refractory seizures eventually leading to mental retardation and death). Radical
      microsurgical resection is not feasible for lesions located within the wall of
      the third ventricle inside the hypothalamus. Frame-based stereotactic
      radiosurgery has been reported as an effective treatment modality for small- to
      medium-size intrahypothalamic hamartomas, providing excellent seizure outcomes
      without lasting complications. This report describes the use of frameless image
      guided robotic radiosurgery (CyberKnife(r) Radiosurgery System) as a first-line
      treatment in two children with catastrophic epilepsy induced by HH. Both patients
      experienced multiple-daily complex partial and gelastic seizures, as well as
      almost daily generalized seizures. The prescribed dose was 16 Gy (to the 65%
      isodose for case I; to the 70% isodose for case II). Lesional volume was 11.5 cc
      (case I) and 8.9 cc (case II). A steady reduction of the seizure frequency and
      severity was achieved after the treatment, starting about three months after the
      treatment. The generalized seizures disappeared within one year, while complete
      resolution of the gelastic seizures required up to 18 months. No seizure
      recurrence and no radiation-induced side effects or complications were witnessed
      over a follow-up period of ten years and eight months (case I) and nine years and
      seven months (case II) since the treatment. CyberKnife radiosurgery proved to be
      a safe and effective non-invasive first-line treatment in these two children with
      catastrophic epilepsy caused by HH.

PMID- 30221097
TI  - Skill Acquisition, Assessment, and Simulation in Minimal Access Surgery: An
      Evolution of Technical Training in Surgery.
AB  - Diminishing resources and expanding technologies, such as minimal access surgery,
      have complicated the acquisition and assessment of technical skills in surgical
      training programs. However, these challenges have been met with both innovation
      and an evolution in our understanding of how learners develop technical
      competence and how to better measure it. As these skills continue to grow in
      breadth and complexity, so too must the surgical education systems' ability. This
      literature review examines and describes the pressures placed on surgical
      education programs and the development of methods to ameliorate them with a focus
      on surgical simulation.

PMID- 30221098
TI  - Intestinal Spirochetosis: An Obscure Cause of Lower Gastrointestinal Bleeding.
AB  - Adherence of spirochetes to the apical membrane of the colonic epithelium has
      been well-described in the literature, but the exact pathogenesis leading to
      symptomatic clinical manifestations is poorly understood. Most cases are found
      incidentally on the pathological evaluation of colonic biopsies taken during
      diagnostic or therapeutic colonoscopies. However, whether the colonization of the
      intestinal mucosa can be attributed to clinical symptoms is a matter of debate.
      Here, we present a case of intermittent hematochezia attributed to the
      overwhelming invasion of the colonic mucosa by intestinal spirochetes.

PMID- 30221099
TI  - Thoracic Discitis in Ankylosing Spondylitis.
AB  - Chronic ankylosing spondylitis can lead to several rare long-term complications
      including cauda equina syndrome and inflammatory discitis especially without
      treatment. These complications are uncommon, but there is evidence that they can
      be treated with anti-tumor necrosis factor (TNF) inhibitors. We present a case of
      a 52-year-old male with a 30-year history of undiagnosed ankylosing spondylitis
      with cauda equina syndrome on initial outpatient presentation with a negative
      lumbosacral magnetic resonance imaging (MRI). He was admitted later that month
      and was found to have thoracic discitis from MRI requiring emergent decompressive
      laminectomy. The neurosurgeon collected a culture of the surgical site which
      showed rare Gram-positive cocci on Gram stain. Infectious disease was consulted,
      and he was started on empiric vancomycin. The culture from the surgical site did
      not grow any organisms. Interventional radiology (IR) aspirated the T7-T8 disk
      area one week later. The initial Gram stain showed rare Gram-negative rods this
      time, and cefepime was added to the patient's antibiotic regimen. The culture
      from the disk aspiration again grew no organisms. Rheumatology was then consulted
      and hypothesized that the patient's discitis could be secondary to inflammation
      from long-standing ankylosing spondylitis. The hospitalist, infectious disease
      specialist, and rheumatologist reviewed the case and recommended a six-week
      course of vancomycin and cefepime despite the negative cultures as an infectious
      etiology could not be excluded. He did show some clinical improvement after
      surgery and was started on adalimumab following completion of empiric
      antibiotics. This case highlights the difficulty in distinguishing between an
      infectious and inflammatory etiology for discitis in the setting of long-standing
      ankylosing spondylitis. The initiation of biological therapy without completely
      excluding the possibility of infection could lead to devastating consequences. It
      will likely be necessary to empirically treat for infection with these cases for
      the foreseeable future until there are more definitive tests to diagnose or
      exclude infectious discitis.

PMID- 30221100
TI  - Case of Missing Plastic: Foreign Body Bronchiectasis.
AB  - Bronchiectasis is a well-known entity where the airways abnormally dilate losing
      their natural function. Most common causes of non-cytic fibrosis bronchiectasis
      in the middle age group include secondary immunodeficiency, aspiration, and
      allergic bronchopulmonary aspergillosis (ABPA). Obstructive foreign body is an
      uncommon cause of bronchiectasis and is often a missed diagnosis in a localized
      disease. Foreign bodies can be missed making the diagnosis and treatment more
      challenging and hence foreign body bronchiectasis should be considered in
      patients presenting with focal disease. Here we describe a patient with a
      retained foreign body that was discovered post lobectomy during gross
      pathological examination of the specimen with no significant aspiration history,
      non-diagnostic imaging of the chest and negative bronchoscopy.

PMID- 30221101
TI  - The Population-Based Longitudinal Chicago Health, Aging, and Social Relations
      Study (CHASRS): Study Description and Predictors of Attrition in Older Adults.

PMID- 30221102
TI  - Measuring social function in diverse cancer populations: Evaluation of
      measurement equivalence of the Patient Reported Outcomes Measurement Information
      System(r) (PROMIS(r)) Ability to Participate in Social Roles and Activities short
      form.
AB  - Conceptual and psychometric measurement equivalence of self-report questionnaires
      are basic requirements for valid cross-cultural and demographic subgroup
      comparisons. The purpose of this study was to evaluate the psychometric
      measurement equivalence of a 10-item PROMIS(r) Social Function short form in a
      diverse population-based sample of cancer patients obtained through the Measuring
      Your Health (MY-Health) study (n = 5,301). Participants were cancer survivors
      within six to 13 months of a diagnosis of one of seven cancer types, and spoke
      English, Spanish, or Mandarin Chinese. They completed a survey on
      sociodemographic and clinical characteristics, and health status. Psychometric
      measurement equivalence was evaluated with an item response theory approach to
      differential item functioning (DIF) detection and impact. Although an expert
      panel proposed that many of the 10 items might exhibit measurement bias, or DIF,
      based on gender, age, race/ethnicity, and/or education, no DIF was detected using
      the study's standard DIF criterion, and only one item in one sample comparison
      was flagged for DIF using a sensitivity DIF criterion. This item's flagged DIF
      had only a trivial impact on estimation of scores. Social function measures are
      especially important in cancer because the disease and its treatment can affect
      the quality of marital relationships, parental responsibilities, work abilities,
      and social activities. Having culturally relevant, linguistically equivalent and
      psychometrically sound patient-reported measures in multiple languages helps to
      overcome some common barriers to including underrepresented groups in research
      and to conducting cross-cultural research.

PMID- 30221103
TI  - Long-term effects of environmentally relevant concentrations of silver
      nanoparticles on major soil bacterial phyla of a loamy soil.
AB  - Background: The growing production and use of engineered AgNP in industry and
      private households make increasing concentrations of AgNP in the environment
      unavoidable. Although we already know the harmful effects of AgNP on pivotal
      bacterial driven soil functions, information about the impact of silver
      nanoparticles (AgNP) on the soil bacterial community structure is rare. Hence,
      the aim of this study was to reveal the long-term effects of AgNP on major soil
      bacterial phyla in a loamy soil. The study was conducted as a laboratory
      incubation experiment over a period of 1 year using a loamy soil and AgNP
      concentrations ranging from 0.01 to 1 mg AgNP/kg soil. Effects were quantified
      using the taxon-specific 16S rRNA qPCR. Results: The short-term exposure of AgNP
      at environmentally relevant concentration of 0.01 mg AgNP/kg caused significant
      positive effects on Acidobacteria (44.0%), Actinobacteria (21.1%) and
      Bacteroidetes (14.6%), whereas beta-Proteobacteria population was minimized by
      14.2% relative to the control (p <= 0.05). After 1 year of exposure to 0.01 mg
      AgNP/kg diminished Acidobacteria (p = 0.007), Bacteroidetes (p = 0.005) and beta
      Proteobacteria (p = 0.000) by 14.5, 10.1 and 13.9%, respectively. Actino- and
      alpha-Proteobacteria were statistically unaffected by AgNP treatments after 1
      year exposure. Furthermore, a statistically significant regression and
      correlation analysis between silver toxicity and exposure time confirmed loamy
      soils as a sink for silver nanoparticles and their concomitant silver ions.
      Conclusions: Even very low concentrations of AgNP may cause disadvantages for the
      autotrophic ammonia oxidation (nitrification), the organic carbon transformation
      and the chitin degradation in soils by exerting harmful effects on the liable
      bacterial phyla.

PMID- 30221104
TI  - A qPCR method to quantify bioavailable phosphorus using indigenous aquatic
      species.
AB  - Background: Bioavailable phosphorus (BAP) represents the sum of phosphorus that
      is readily available for algae growth and is useful to indicate the severity of
      eutrophication in aquatic environments. Results: Here, a quantitative real-time
      PCR (qPCR)-based bioassay was developed to quantify BAP using the indigenous
      cyanobacterium species Anabaena sp. of Lake Tai, a large and shallow eutrophic
      lake in the Yangtze Valley, China. Primers were designed to quantify the gene
      expression of alkaline phosphatase (phoA/phoA-like) and phosphate transporter
      (pst1) genes of Anabaena. The specificity and efficiency of the primer sets were
      evaluated by gel electrophoresis and real-time PCR. The results showed that the
      primers developed here could successfully be used to measure BAP in the water.
      The linear range of BAP measurements by the pst1 gene after 2 h incubation was
      0.125-2.00 mg/L. Then, the qPCR-based bioassay was applied to analyze water
      samples from Tai Lake, which had BAP levels in the range of 0.239-0.459 mg/L.
      Conclusions: The qPCR-based bioassay represents a promising biomonitoring tool
      that can quantify phosphorus bioavailability in aquatic environments.

PMID- 30221107
TI  - Transcriptome analysis and physiological responses of the potato plantlets in
      vitro under red, blue, and white light conditions.
AB  - Light is an important factor for plant development and has serious effects on the
      growth, production and quality of potatoes. However, the physical and molecular
      mechanisms by which potato plantlets cope with different light qualities are not
      understood. In this study, the potato "Zhuanxinwu", which is a germplasm potato
      resource with a high anthocyanin content, was used for physiological and
      transcriptome profiling analyses to uncover the different mechanisms that occur
      in response to blue, red and white light conditions, with the white light
      condition serving as the control. Multiple growth indexes, protective enzyme
      activity and metabolite accumulation were measured. The results indicated that
      white light promoted a shift in biomass allocation away from tubers to leaves to
      enhance dry leaf matter and reduce tuber fresh/dry weight relative to the effects
      of blue or red light. The leaf area and anthocyanin content values were greater
      for plants grown in blue light than those grown in white or red light, suggesting
      that combinations of different spectra were more conducive to regulating potato
      growth. A total of 2220 differentially expressed genes (DEGs) were found among
      the three samples, and the DEGs in the three comparison sets were analyzed. A
      total of 1180 and 984 DEGs were identified in the red light (Red) and blue light
      (Blue) conditions compared to the control condition, respectively, and 359 DEGs
      overlapped between the two comparison sets (Blue_vs_White and Red_vs_White).
      Interestingly, the 24 most common overlapped DEGs were involved in
      photosynthesis, respiration, and reactive oxygen species (ROS) scavenging. Of
      these DEGs, four genes involved in photosynthesis and two genes involved in
      pigment synthesis were highly expressed, implying that some genes could be
      implemented to cope with different light spectra by regulating the expression of
      DEGs involved in the corresponding metabolic pathways. In conclusion, our study
      characterizes physiological responses of potato to different light qualities and
      identifies potential pathways and candidate genes involved in these responses,
      thus providing a basis for further research on artificial light regulation of
      potato plant growth.

PMID- 30221106
TI  - Multiple biomarker responses in caged benthic gastropods Bellamya aeruginosa
      after in situ exposure to Taihu Lake in China.
AB  - Background: Freshwater sediments have been recognized as a long-term sink and
      potential source for environmental pollutants released into the aquatic
      ecosystems. In this study, the sediment quality of Taihu Lake, which is
      susceptible to anthropogenic contamination, was assessed by a combination of
      chemical analytical and biological end points. Specifically, the snail Bellamya
      aeruginosa was caged in situ at two locations representing different pollution
      levels for different exposure times (7, 14 and 21 days). At each of these time
      points, biochemical parameters, i.e., phase I biotransformation enzymes
      ethoxyresorufin-O-deethylase (EROD), the antioxidant enzymes superoxide dismutase
      and catalase, reactive oxygen species, protein carbonyl content and lipid
      peroxidation, were evaluated in the hepatopancreas of snails. In addition,
      surface sediments were collected for analysis of contaminants of concern,
      including inorganic pollutants, organochlorine pesticides, polychlorinated
      biphenyls and polybrominated diphenyl ethers. Results: Chemical analyses revealed
      that sediments from Taihu Lake were contaminated with trace elements and organic
      pollutants. Concentrations of trace elements (Cu, Ni and As) and
      organochlorinated pesticides (4,4'-DDE) exceeded their corresponding threshold
      effect level according to the sediment quality assessment values for freshwater
      ecosystems in Canada, indicating that adverse biological effects may occur. All
      biomarkers, except EROD activity, were induced in snails during all exposure
      times. The integrated biomarker response index (IBR) indicated that during the
      initial exposure phase (7 days), B. aeruginosa were subjected to significant
      environmental stress, which diminished during later sampling time points.
      Conclusions: Results showed that IBR correlated well with the levels of
      environmental contaminants, demonstrating the applicability of this biomonitoring
      approach to complex environmental exposure scenarios.

PMID- 30221105
TI  - Towards a holistic and solution-oriented monitoring of chemical status of
      European water bodies: how to support the EU strategy for a non-toxic
      environment?
AB  - The definition of priority substances (PS) according to the Water Framework
      Directive (WFD) helped to remove many of these chemicals from the market and to
      reduce their concentrations in the European water bodies. However, it could not
      prevent that many of these chemicals have been replaced by others with similar
      risks. Today, monitoring of the PS-based chemical status according to WFD covers
      only a tiny fraction of toxic risks, extensively ignores mixture effects and
      lacks incentives and guidance for abatement. Thus, we suggest complement this
      purely status-related approach with more holistic and solution-oriented
      monitoring, which at the same time helps to provide links to the ecological
      status. Major elements include (1) advanced chemical screening techniques
      supporting mixture risk assessment and unraveling of source-related patterns in
      complex mixtures, (2) effect-based monitoring for the detection of groups of
      chemicals with similar effects and the establishment of toxicity fingerprints,
      (3) effect-directed analysis of drivers of toxicity and (4) to translate chemical
      and toxicological fingerprints into chemical footprints for prioritization of
      management measures. The requirement of more holistic and solution-oriented
      monitoring of chemical contamination is supported by the significant advancement
      of appropriate monitoring tools within the last years. Non-target screening
      technology, effect-based monitoring and basic understanding of mixture assessment
      are available conceptually and in research but also increasingly find their way
      into practical monitoring. Substantial progress in the development, evaluation
      and demonstration of these tools, for example, in the SOLUTIONS project enhanced
      their acceptability. Further advancement, integration and demonstration,
      extensive data exchange and closure of remaining knowledge gaps are suggested as
      high priority research needs for the next future to bridge the gap between
      insufficient ecological status and cost-efficient abatement measures.

PMID- 30221108
TI  - Essential oils from tropical medicinal herbs and food plants inhibit biofilm
      formation in vitro and are non-cytotoxic to human cells.
AB  - The biofilm inhibition and eradication potential of essential oils (EOs)
      extracted from six tropical medicinal herbs and food plants [Psiadia arguta (PA),
      Psiadia terebinthina (PT), Citrus grandis (CGp), Citrus hystrix (CH), Citrus
      reticulata (CR), and Cinnamomum zeylanicum (CZ)] were assessed. The mechanism of
      inhibition was studied via quenching of efflux pump. Cytotoxicity was evaluated
      using Artemia salina assay and cell lines [human cervix carcinoma (HeLa), human
      lung fibroblast (MRC-5), and murine melanoma (B16F10)]. EOs of CH, CR, PA, and PT
      were found to be prospective antibiofilm agents (IC50 of 0.29, 0.59, 0.22, and
      0.11 mg/mL against Staphylococcus epidermidis; 0.39, 0.54, 0.09, and 0.13 mg/mL
      against Escherichia coli; and 0.54, 0.90, 0.44 and 0.51 mg/mL against Candida
      albicans for CH, CR, PA, and PT, respectively). The simultaneous actions of the
      EOs and efflux pump inhibitor impacted on the resistance of the biofilms. LC50 of
      the EOs ranged from 223 to 583 ug/mL against A. salina. The non-cytotoxic
      concentration of the EOs varied from 200 to 300 ug/mL (HeLa and MRC-5), and 150
      200 ug/mL (B16F10). EOs from these tropical medicinal herbs and food plants are
      useful sources of new antimicrobials with low cytotoxicity which could open new
      horizons in the drug development process.

PMID- 30221109
TI  - Enzymatic hydrolysis of cellulosic materials using synthetic mixtures of purified
      cellulases bioengineered at N-glycosylation sites.
AB  - Mutant forms of recombinant endoglucanase II (EG II, N194A), cellobiohydrolase I
      (CBH I, N45A) and cellobiohydrolase II (CBH II, N219A) from Penicillium
      verruculosum with enhanced cellulase activities, achieved by engineering of
      enzyme N-glycosylation sites in our previous studies, were used as components of
      the binary and ternary mixtures of cellulases in hydrolysis of Avicel and milled
      aspen wood. Using the engineered forms of the enzymes at a dosage of 10 mg/g
      substrate resulted in significant boosting of the glucose release from cellulose
      in the presence of excess beta-glucosidase relative to the performance of the
      corresponding wild-type mixtures at the same loading. The boosting effects
      reached 11-40% depending on the reaction time and substrate type. In hydrolysis
      of both cellulosic substrates by the binary mixtures of cellulases, all the
      enzyme pairs exhibited synergism. The magnitude of the synergistic effects (Ks)
      did not depend notably upon the induced mutations in the enzymes, and they were
      in the range of 1.3-1.8 for the combinations of EG II with CBH I (or CBH II), and
      2.3-2.9 for the CBH I-CBH II pair. The results of this study should provide a
      basis for the development of a more effective fungal strain capable of producing
      cellulase cocktails with enhanced hydrolytic performance against lignocellulosic
      materials.

PMID- 30221110
TI  - Diversity of bacterial endophytes in Panax ginseng and their protective effects
      against pathogens.
AB  - Although endophytic bacteria are known to colonize Panax ginseng, little is known
      about their diversity and roles. We addressed in the present study by comparing
      endophytic bacterial populations in P. ginseng plants of different ages (2-6
      years) and in various tissue types (root, stem, leaf, and flower stalk). A total
      of 116 strains assigned to 42 species were identified by 16S rDNA sequencing. The
      predominant phylum was Firmicutes. Two-year-old ginseng plants and root tissues
      showed the greatest diversity of endophytic bacteria, with Bacillales being the
      predominant order. The antifungal activity of isolates against two pathogens,
      Cylindrocarpon destructans and/or Botrytis cinerea, was evaluated in dual-culture
      assays. In total, 28 strains showed antifungal activity with PgBE14 (Bacillus
      amyloliquefaciens), PgBE40 (B. megaterium), PgBE39, PgBE45 (Pseudomonas
      frederiksbergensis), and PgBE42 (Staphylococcus saprophyticus) inhibiting both
      pathogens. These results improve our understanding of the structure and diversity
      of endophytic bacterial communities of P. ginseng and identify strains with
      antifungal activity that have potential applications as biocontrol agents.

PMID- 30221111
TI  - Bio-production of novel water-soluble yellow pigment from Aspergillus sp. and
      exploring its sustainable textile applications.
AB  - In the present study, 40 pigment-producing microbes were isolated from various
      soil sources. Among these, a novel water-soluble yellow pigment-producing fungal
      isolate (MBYP1) was identified as Aspergillus sp. through ITS gene sequencing.
      The maximum pigment yield (UA430nm, 12.45 +/- 0.5 g/l) was obtained when strain
      MBYP1 was cultured under optimum conditions (28  degrees C and pH 5.5 under
      static condition). Subsequently, the pigment was purified through gel
      chromatography and high-performance liquid chromatography (HPLC).
      Characterization of purified pigment through UV-Vis and liquid chromatography
      mass spectrometry (LC-MS) reveal maximum absorbance at 430 nm and molecular mass
      of 301 m/z, respectively. Further, the pigment exhibited a maximum dyeing
      capacity of up to 80% irrespective of mordant. Toxicity evaluation of purified
      pigment with zebra fish model system reported an IC50 value of 710 ug/mL. Pigment
      antioxidant ability was established by DPPH (35.7 ug/mL) and phosphomolybdenum
      assay (226.61 mg/g) thus ascertaining improvised light fastness of dyed fabric.
      Moreover, lack of antimicrobial activity (up to 40 ug/mL) improves pigment bio
      degradability. In collective, the novel yellow pigment from Aspergillus sp. MBYP1
      strain was found to be an eco-friendly alternative to synthetic dye for potential
      applications in textile industries.

PMID- 30221112
TI  - Curcumin-mediated effects on anti-diabetic drug-induced cardiotoxicity.
AB  - The present study was designed to compare the cardiotoxicity of two very commonly
      used anti-diabetic drugs namely pioglitazone (Pio) and metformin (Met); and to
      study the effects of curcumin (Curc) against these drug-induced cardiotoxicity.
      Curc, being an anti-oxidant molecule and having cardio-protective potential, can
      have promising synergistic effects in reducing the cardiac stress induced by anti
      diabetic therapies. Various dose and time-dependent cell viability and oxidative
      stress assays were conducted to study cardiotoxic side-effects and Curc-mediated
      effects in cardiomyoblasts. Effects of Curc were also studied in hyperglycaemia
      induced cardiac stress in the presence of drugs. Quantitative assays for cell
      growth, reactive oxygen species (ROS) generation, lipid peroxidation and
      mitochondrial permeability followed by anti-oxidant enzymes and caspases activity
      assays were done to study the mechanism of action of the induced cardiotoxicity.
      Significant dose and time mediated deleterious effects of Pio and Met were
      witnessed. Oxidative stress studies showed a remarkable increase in ROS with
      increasing dose of anti-diabetic drugs. Increased caspase activity and altered
      mitochondrial integrity were also witnessed in presence of Met and Pio in
      cardiomyoblasts. These alterations were found to be significantly reduced when
      treated with Curc simultaneously. The study confirms that Met and Pio exert toxic
      effects on cardiac cells by generating oxidative stress. Curc, being an anti
      oxidative molecule, can suppress this effect and, therefore, can be used as a
      supplement with anti-diabetic drugs to suppress the induced cardiac stress.

PMID- 30221113
TI  - Efficient purification of a recombinant tag-free thermostable Kluyveromyces
      marxianus uricase by pH-induced self-cleavage of intein and expression in
      Escherichia coli.
AB  - Uricase as an important healthcare-related protein is extensively used in the
      treatment of tumor lysis syndrome and in the manufacture of serum uric-acid
      diagnostic kits. In this study, a gene of a new thermostable uricase (KmUOX) was
      cloned from thermotolerant yeast Kluyveromyces marxianus. The uricase was fused
      with a self-cleaving intein and cellulose-binding affinity tag and expressed in
      Escherichia coli BL21 (DE3). Through the binding to inexpensive cellulose and in
      situ intein cleavage induced by a pH change, tag-free uricase (KmUOX) was
      efficiently purified with a 77.11% yield via a single-step column purification
      strategy. This tag-free uricase showed Km, Vmax, and Kcat values of 67.60 uM,
      56.35 uM/(min mg), and 32.74 S-1, respectively. Furthermore, this pure uricase
      was relatively thermostable and retained 79.75% of activity when incubated at 40 
      degrees C for 90 h. Thus, this pH-induced self-cleavable intein system combined
      with a cellulose matrix for affinity chromatography is proven here to be an
      effective and low-cost method for recombinant-uricase purification. Moreover, the
      stability of KmUOX makes it useful for clinical applications.

PMID- 30221115
TI  - Improved production of cellulase by Trichoderma reesei (MTCC 164) from coconut
      mesocarp-based lignocellulosic wastes under response surface-optimized condition.
AB  - Experimental investigations were carried out to develop economic production
      process of cellulase using coconut mesocarp as an inexpensive lignocellulosic
      inducer while replacing commercial cellulose. Cellulase production was initially
      investigated from commercial cellulose in different submerged conditions using
      Trichoderma reesei (MTCC 164). Maximum enzyme production was achieved 6.3 g/l
      with activity level 37 FPU/ml in the condition where cellulose to water content
      ratio was maintained at 5:35 (W/V). To achieve similar maximum production of
      cellulase from coconut mesocarp, response surface methodology was implemented to
      optimize most influencing parameters. Most influencing nutritional parameters
      such as coconut mesocarp, glucose and peptone were optimized in the concentration
      ranges of 35 g/l, 35 g/l and 25 g/l, respectively. Selecting optimized parameter
      values, fermentations were conducted inside the fermenter with 2 L operating
      volume to ensure high concentration and activity profiles of enzyme. Enzyme
      concentration was achieved 7.20 g/l after 96 h of batch fermentation with
      specific activity levels of 42 FPU/ ml and CMCase 75 U/ml. Enzyme concentration
      was further improved to 9.58 g/l with activity levels of 54 FPU/ml and CMCase 93
      U/ml by adopting sequential feeding of coconut mesocarp in fed-batch fermentation
      mode. The presence of pure cellulase in the sample was confirmed by FTIR
      analysis.

PMID- 30221114
TI  - Microbial maceration: a sustainable approach for phytochemical extraction.
AB  - A rapid change in the lifestyle has witnessed poor health with the increased
      incidences of numerous diseases in the recent years, and ultimately increasing
      the demand of nutritious foods containing phytochemicals. A wide range of
      phytochemicals (secondary metabolites) is being synthesized in plants, which
      influence the human health upon consumption as dietary component. Recently, a
      number of the technologies (conventional and non-conventional methods) have been
      standardized by the different researchers for the extraction of these
      phytochemicals depending upon the raw material. However, selection of extraction
      method for commercial use depends upon various factors such as extraction
      efficiency, time required, and cost of operation. Considering these factors,
      microbial maceration is one of the viable approaches which is easy to handle,
      cost-effective, energy efficient, less hazardous and having high extraction rate.
      Recently, researchers have utilized this technique for the maceration of
      different plant-based substrates (such as legumes, cereals, pulses, fruits and
      vegetables) and their respective wastes for the efficient extraction of numerous
      phytochemicals with increased efficiency. However, scale up studies and analysis
      of toxic compounds produced by microbes are still a lacking field and need to be
      explored further by the researchers and industrialists to bring it into reality.
      Therefore, the present review aims to document the recent findings related to
      microbial maceration in a crisp way to provide the complete information to the
      readers.

PMID- 30221116
TI  - A novel and rapid method for fatty acid preparation by the lipase-catalyzed
      hydrolysis of Phoenix tree seeds.
AB  - Fatty acids are the precursors for the production of fuels, oleochemicals and
      special health care products. In this study, a novel rapid method for fatty acid
      (FA) preparation by the enzymatic hydrolysis of Phoenix tree seed, an undeveloped
      woody oil seed, was developed. High-temperature GC with flame ionization detector
      (FID) and the hydrolysis ratio were used to monitor reaction progress. Enzyme
      screening and the effect of reaction variables on the hydrolysis of seeds were
      evaluated and optimized by response surface methodology. The results showed that
      among the tested enzymes, Lipozyme TLIM showed the greatest amount of hydrolysis
      of Phoenix tree seed. FAs can be rapidly prepared by one-step hydrolysis of
      Phoenix tree seeds using Lipozyme TLIM as the biocatalyst. Under the optimized
      conditions (6% enzyme load, 1:8 mass ratio of seed to water, 47.7  degrees C and
      16 min), the maximum hydrolysis ratio (96.4 +/- 1.1%) can be achieved. The effect
      of reaction variables on the hydrolysis decreased in the following order:
      reaction time > enzyme load > substrate ratio of seed to water > reaction
      temperature. This work provides a novel and rapid method for FA preparation from
      oil seeds.

PMID- 30221117
TI  - Biofabricated silver nanoparticles incorporated polymethyl methacrylate as a
      dental adhesive material with antibacterial and antibiofilm activity against
      Streptococcus mutans.
AB  - In this study, polymethyl methacrylate (PMMA) thin films incorporated with
      biofabricated silver nanoparticles were used to evaluate the in vitro
      antimicrobial and antibiofilm activity against the cariogenic bacterium
      Streptococcus mutans. For this, silver nanoparticles (AgNPs) were generated using
      Bacillus amyloliquefaciens SJ14 culture (MAgNPs) and extract from Curcuma
      aromatica rhizome (CAgNPs). The AgNPs were further characterized by UV-Vis
      spectroscopy and high-resolution transmission electron microscopy. The minimum
      inhibitory concentration, minimum bactericidal concentration and antibiofilm
      activity of AgNPs against S. mutans were also assessed. Here, MAgNPs were found
      to have superior antimicrobial activity when compared to CAgNPs. The MAgNPs and
      CAgNPs also demonstrated 99% and 94% inhibition of biofilm formation of S. mutans
      at concentrations of 3 ug/mL and 50 ug/mL, respectively. The AgNPs were further
      incorporated into PMMA thin films using solvent casting method. The thin films
      were also characterized by scanning electron microscopy and UV-Vis spectroscopy.
      Subsequently, both PMMA/MAgNPs and PMMA/CAgNPs nanocomposite thin films were
      subjected to antimicrobial and antibiofilm analysis. The microbicidal activity
      was found to be higher for the PMMA/MAgNPs thin film, which highlights the
      potency of microbially synthesized AgNPs as excellent agents to inhibit
      cariogenic bacteria from colonising dental restorative material.

PMID- 30221119
TI  - Same but Different? Developmental Pathways to Demonstrative Targeted Attacks -
      Qualitative Case Analyses of Adolescent and Young Adult Perpetrators of Targeted
      School Attacks and Jihadi Terrorist Attacks in Germany.
AB  - Analysis of incidents over the past ten years in Germany reveals that the
      boundaries between targeted attacks in schools and terrorist attacks are starting
      to blur. Bockler, Leuschner, Roth, Zick, and Scheithauer (2018) recently
      presented a set of hypotheses about similarities between the developmental
      pathways of school attackers and lone actor terrorists. To date there is only a
      small body of empirical research comparing these two forms of targeted violence
      in depth. In order to fill this gap, this article presents findings from a
      qualitative analysis of prosecution files comparing the developmental pathways of
      German school attackers (N = 7; age range: 13 to 23) and Jihadi attackers (N = 7;
      age range: 21 to 28 years) who committed their attacks between 2000 and 2013.
      Using theoretical coding and constant case comparison, the contribution shows
      that the two phenomena have overlaps in which developmental processes and social
      mechanisms are similar. Both school attackers and Jihadi attackers frame their
      act of violence using cultural scripts and perform the attack on a public stage
      where victims are attacked not on the basis of personal conflicts but because of
      their symbolic meaning. Taking into account the similarities in the perpetrators'
      developmental pathways, the authors propose that it might be more fruitful from
      an operational perspective to discuss severe target school violence and terrorist
      attacks under a common concept of demonstrative violence than to artificially
      assign them to exclusive classes of violence.

PMID- 30221118
TI  - An investigation of the HMGR gene and IPI gene expression in black caraway
      (Bunium persicum).
AB  - Black caraway is of great importance for its terpene compounds. Many genes are
      involved in the biosynthesis of secondary metabolites in medicinal plants. For
      this study, black caraway seeds were collected from five different regions, i.e.
      [Isfahan; Kerman (Khabr); Semnan; Kerman (Sirch); and Hormozgan]. The black
      caraway seed oil was extracted and analyzed by means of the gas chromatography
      method. There was a negatively significant correlation (p <= 0.05) observed
      between cuminaldehyde and gammaterpinene compounds. 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMGR) and isopentenyl pyrophosphate isomerase (IPI) play an
      important role in the biosynthesis of secondary metabolites. Appropriate primers
      were designed for these genes based on the conserved regions in other plants.
      Amplified fragments were then sequenced. Blastn results indicated the similarity
      of the high RNA sequences between new sequences and other HMGR and IPI gene
      sequences in GenBank, and it also identified the HMGR and IPI gene sequences of
      B. persicum. A fragment of the HMGR gene with KJ143741 number was recorded in the
      gene bank. Quantitative PCR showed that the relative expression of two genes in
      different growth stages of B. persicum was significantly different between the
      germination stage and the multi-leaf stage, and also between the germination
      stage and the flowering stage (p < 0.05); however, there was no significant
      difference observed between the flowering stage and the multi-leaf stage. The
      results indicated that the expression of HMGR increased from the germination
      stage to the adult plant, and then it got stable until the flowering stage; in
      the same vein, the expression of IPI increased continuously from the germination
      stage to the flowering stage. The expression of HMGR and IPI genes occurred
      differently at the germination stage of five ecotypes. The Hormozgan ecotype
      showed the least expression rate.

PMID- 30221120
TI  - Nonmedical Prescription Drug Use among Adolescents: Global Epidemiological
      Evidence for Prevention, Assessment, Diagnosis, and Treatment.
AB  - Purpose of review: This paper reviews the most recent epidemiological evidence on
      adolescent NMPD use. Particular attention is given to prevention, assessment and
      diagnosis of disorder, and treatment. Recent findings: While international in
      scope, global evidence is only available for NMPD use, morbidity and mortality
      estimates. Prevention strategies, assessment and treatment are U.S.-centric. The
      literature on prevention strategies lacks high-quality evidence. Assessment,
      diagnosis and treatment of NMPD use disorder have more robust evidence bases.
      Despite this, screening for NMPD (and other drug) use disorders is infrequent and
      insensitive, leading to incomplete treatment provision. Treatments are shown to
      be safe and effective, but disparities in provision prevent wide-scale
      amelioration of the adolescent NMPD use problem. Summary: Mental health care
      professionals and primary care physicians with adolescent patient populations
      should become involved in preventative strategies mentioned in this review.
      Additionally, higher screening rates will lead to less downstream problems
      related to NMPD use.

PMID- 30221121
TI  - Approaches for Effective Clinical Application of Stem Cell Transplantation.
AB  - Purpose of Review: This review highlights problems related to translation of
      advanced therapy medicinal products (ATMPs) from bench to bedsite. Regenerative
      medicine within the current regulatory frame reveals common hitches in the course
      of development, translation, and clinical application. This paper suggests
      outlining a path from the few examples of successfully approved vs unsuccessful
      advanced therapies. Recent Findings: In the multitude of ongoing studies, few of
      them achieved positive results with a final treatment available to patients; this
      result was possible due to multidisciplinary teams working together from the
      beginning of the development and during the hard route to standardization and
      clinical application. Summary: The root of success of an advanced therapy
      requires not only the inescapable scientific and biological knowledge but also
      requires several contributions as regulatory, ethical, medical, and bio
      engineering expertise, from the real beginning. A strong scientific rationale and
      an integrated network of expertises would contribute to a successful investment
      of available resources in advanced therapy medicinal products and to a greater
      confidence in future medicine.

PMID- 30221122
TI  - Duration of Allergen Immunotherapy for Long-Term Efficacy in Allergic
      Rhinoconjunctivitis.
AB  - Rationale: Subcutaneous and sublingual immunotherapy are effective for allergic
      rhinitis. An important question is whether allergen immunotherapy provides a
      sustained clinical effect after treatment cessation. In view of potential side
      effects, cost and the necessary patient commitment, long-term benefit is an
      important consideration for the recommendation of immunotherapy over standard
      pharmacotherapy. Purpose of review: In this review, we analyse the existing
      evidence for long-term effects of both routes of administration in the context of
      double-blind, placebo-controlled, randomised clinical trials that included a
      follow-up phase of at least 1 year after treatment cessation. Recent findings:
      Overall, evidence suggests that 3 years of either subcutaneous or sublingual
      immunotherapy result in clinical benefit and immunological changes consistent
      with allergen-specific tolerance sustained for at least 2-3 years after treatment
      cessation. Summary: The data presented here support recommendations in
      international guidelines that both routes of administration should be continued
      for a minimum of 3 years. Gaps in the evidence remain regarding the long-term
      efficacy of immunotherapy for perennial rhinitis and studies performed in
      children.

PMID- 30221123
TI  - Placebo effects in allergen immunotherapy: an experts' opinion.
AB  - Placebo effects are common in medicine. Randomised clinical trials help us to
      understand their magnitude in different therapies. There are particular problems
      with placebo effects in allergen immunotherapy (AIT) as it is difficult to blind
      the active treatment and the endpoints are largely subjective. This may explain
      why large placebo effects are often found in AIT trials. Patients receiving open
      label AIT get the benefit of the active and placebo components but it can be
      difficult to say how much benefit is due to the active component. The use of
      active placebos has been proposed but brings its own problems (ethical and
      scientific). An EAACI Task Force has been established to address these issues.
      Here we review the current literature on the placebo effect in general, with a
      special focus on AIT trials, and indicate what we believe to be important
      considerations and unmet needs in AIT trial design.

PMID- 30221125
TI  - Adding ReputationRank to member promotion using skyline operator in social
      networks.
AB  - Background: To identify potential stars in social networks, the idea of combining
      member promotion with skyline operator attracts people's attention. Some
      algorithms have been proposed to deal with this problem so far, such as skyline
      boundary algorithms in unequal-weighted social networks. Methods: We propose an
      improved member promotion algorithm by presenting ReputationRank based on
      eigenvectors as well as Influence and Activeness and introduce the concept of
      skyline distance. Furthermore, we perform skyline operator over non-skyline set
      and choose the infra-skyline as our candidate set. The added ReputationRank helps
      a lot to describe the importance of a member while the skyline distance assists
      us to obtain the necessary condition for not being dominated so that some
      meaningless plans can be pruned. Results: Experiments on the DBLP and WikiVote
      datasets verify the effectiveness and efficiency of our proposed algorithm.
      Conclusions: Treating the infra-skyline set as candidate set reduces the number
      of candidates. The pruning strategies based on dominance and promotion cost
      decrease the searching space.

PMID- 30221124
TI  - Positive and negative AIT trials: What makes the difference?
AB  - Background: Allergen immunotherapy has proven to be efficacious in allergic
      rhinitis and asthma. However, results from randomised clinical trials may vary
      substantially. Clinical trials may unexpectedly fail. The purpose of this review
      is to discuss the possible factors that may contribute to a successful or
      unsuccessful study. Methods: Descriptive review exploring the possible causes of
      negative outcomes in allergen immunotherapy trials. Results: A series of factors
      may lead to negative results. Among of these are underpowering of the study, low
      allergen content in tested extracts, insufficient allergen exposure during
      monitoring and recruitment of inappropriate patients. In addition, the choice of
      the primary endpoint may be critical. Discussion: A clinical trial aims to
      evaluate the efficacy of an agent. However, studies with potential effective
      compounds may fail because of methodical issues. Sometimes, they are the cause of
      discrepancies between successful phase II and unsuccessful phase III trials. To
      understand more about failure of studies, investigators and editors should be
      encouraged to publish negative trials.

PMID- 30221126
TI  - Sub-Angstrom electric field measurements on a universal detector in a scanning
      transmission electron microscope.
AB  - Scanning transmission electron microscopy (STEM) excels in accessing atomic-scale
      structure and chemistry. Enhancing our ability to directly image the
      functionalities of local features in materials has become one of the most
      important topics in the future development of STEM. Recently, differential phase
      contrast (DPC) imaging has been utilized to map the internal electric and
      magnetic fields in materials from nanoscale features such as p-n junctions,
      skyrmions, and even from individual atoms. Here, we use an ultra-low noise SCMOS
      detector in as the diffraction plane camera to collect four-dimensional (4D)
      datasets. The high angular resolution, efficient high-SNR acquisition, and
      modifiability of the camera allow it to function as a universal detector, where
      STEM imaging configurations, such as DPC, bright field, annular bright field, and
      annular dark field can all be reconstructed from a single 4D dataset. By
      examining a distorted perovskite, DyScO3, which possesses projected lattice
      spacings as small as 0.83 A, we demonstrate DPC spatial resolution almost
      reaching the information limit of a 100 keV electron beam. In addition, the
      perovskite has ordered O-coordinations with alternating octahedral tilts, which
      can be quantitatively measured with single degree accuracy by taking advantage of
      DPC's sensitivity to light atoms. The results, acquired on a standard Ronchigram
      camera as opposed to a specialized DPC detector, open up new opportunities to
      understand and design functional materials and devices that involve lattice and
      charge coupling at nano- and atomic-scales.

PMID- 30221128
TI  - Study of Long-Term Biocompatibility and Bio-Safety of Implantable Nanogenerators.
AB  - Implantable nanogenerator (i-NG) has shown great promises for enabling self
      powered implantable medical devices (IMDs). One essential requirement for
      practical i-NG applications is its long-term bio-compatibility and bio-safety.
      This paper presents a systematic study of polydimethylsiloxane (PDMS) and
      PDMS/Parylene-C packaged Polyvinylidene fluoride (PVDF) NGs implanted inside
      female ICR (Institute of Cancer Research) mice for up to six months. The PVDF NG
      had a stable in vitro output of 0.3 V when bended for 7200 cycles and an in vivo
      output of 0.1V under stretching. Multiple advanced imaging techniques, including
      computed tomography (CT), ultrasound, and photoacoustic were used to characterize
      the embedded i-NGs in vivo. The i-NGs kept excellent adhesion to the adjacent
      muscle surface, and exhibited stable electrical output during the entire examine
      period. No signs of toxicity or incompatibility were observed from the
      surrounding tissues, as well as from the whole body functions by pathological
      analyses and blood and serum test. The PDMS package was also able to effectively
      insulate the i-NG in biological environment with negligible stray currents at a
      pA scale. This series of in-vivo and in-vitro study confirmed the biological
      feasibility of using i-NG in vivo for biomechanical energy harvesting.

PMID- 30221127
TI  - The Role of Self-Regulation in Academic and Behavioral Paths to a High School
      Diploma.

PMID- 30221130
TI  - Ultrastructure Study of the Stored Lipid Reserves in Gyrodactylus gasterostei
      (Monogenea) Using Confocal and Transmission Electron Microscopy.
AB  - This study examines the distribution and depletion of stored lipids in
      Gyrodactylus gasterostei Glaser, 1974, migrating off its three-spine stickleback
      host Gasterosteus aculeatus L., with the prospect that it might prove informative
      for interpreting the biology of other gyrodactylids species more generally.
      Nonfeeding life cycle stages, such as the dispersal stages of parasites, are
      dependent for survival upon finite energy reserves gathered during feeding
      phases. Thus, those individuals with more limited reserves will die sooner and
      consequently have less time available to find a new host once detached. At this
      stage, the principal energy reserves in gyrodactylids are stored as large lipid
      droplets. Confocal laser scanning microscopy has been used to investigate the
      distribution of lipid droplets in Gyrodactylus, which have migrated off their
      fish host, testing the hypothesis that these droplets function as a proxy for the
      nutritional state. This study demonstrated that the lipid droplets were
      particularly associated with the gut and that there is a significant variability
      in the volume of stored lipid carried out by each individual. Transmission
      electron microscopy showed that gyrodactylids carry lipid droplets at all stages
      of their life cycle, including at release from the birth pore. It is likely that
      transferring worms requires stored energy reserves to survive in the event of
      failure to establish contact with a new host. These reserves could allow the
      parasite to survive without a host for several days.

PMID- 30221129
TI  - Expression of alternative NADH dehydrogenases (NDH-2) in the phytopathogenic
      fungus Ustilago maydis.
AB  - Type 2 alternative NADH dehydrogenases (NDH-2) participate indirectly in the
      generation of the electrochemical proton gradient by transferring electrons from
      NADH and NADPH into the ubiquinone pool. Due to their structural simplicity,
      alternative NADH dehydrogenases have been proposed as useful tools for gene
      therapy of cells with defects in the respiratory complex I. In this work, we
      report the presence of three open reading frames, which correspond to NDH-2 genes
      in the genome of Ustilago maydis. These three genes were constitutively
      transcribed in cells cultured in YPD and minimal medium with glucose, ethanol, or
      lactate as carbon sources. Proteomic analysis showed that only two of the three
      NDH-2 were associated with isolated mitochondria in all culture media. Oxygen
      consumption by permeabilized cells using NADH or NADPH was different for each
      condition, opening the possibility of posttranslational regulation. We confirmed
      the presence of both external and internal NADH dehydrogenases, as well as an
      external NADPH dehydrogenase insensitive to calcium. Higher oxygen consumption
      rates were observed during the exponential growth phase, suggesting that the
      activity of NADH and NADPH dehydrogenases is coupled to the dynamics of cell
      growth.

PMID- 30221131
TI  - Structural and Optical Properties Correlated with the Morphology of Gold
      Nanoparticles Embedded in Synthetic Sapphire: A Microscopy Study.
AB  - This work reports on the electron microscopy analysis of the structure and
      morphology of gold nanoparticles produced by ion implantation as well as their
      relationship to their optical properties. Metalic nanoparticles by ion
      implantation are usually spherical and formed beneath the surface of a dielectric
      matrix. In this experiment, the matrix was sapphire. After high-energy Si ion
      irradiation, the gold nanoparticles were elongated into prolate spheroids. Since
      the nanoparticles are embedded in a dielectric matrix, secondary electron imaging
      in a JEOL JSM-7800F at low voltage did not allow their analysis. This work
      proposes an analysis using backscattered electron imaging in a field emission
      scanning electron microscopy at higher voltages (20 kV) to explore the morphology
      of the embedded nanoparticles. The samples were observed by cross-sectional view
      as well as a top view of the surface of the sapphire matrix for exploration and
      recognition of their morphology, dimensions, distribution, and composition. The
      analysis was extended by means of Rutherford backscattering spectrometry, X-ray
      diffraction, and optical extinction spectroscopy. The nanoparticles exhibited
      structural and optical properties correlated directly to the morphology observed
      by microscopy. The beam interaction with the sample and the used parameters was
      simulated in the CASINO code, from which the depth of exploration with distinct
      parameters used in microscopy analysis was estimated.

PMID- 30221132
TI  - Scanning Electron Microscopes/Silicon Drift Detector-Energy Dispersive
      Spectroscopy: An Analytical Tool to Identify Waterborne Microminerals Pickup in
      Human Scalp Hair Cuticle due to Water Quality.
AB  - Background and Significance: Still vast majority of the population in urban and
      rural set up using varied water quality for their day today washing of their hair
      in many parts of the countries may suffer or experience rough hair or uncombable
      syndrome. The quality of maintaining healthy hair may be impaired due to salty
      ions from water sources, dyes, or pollutants etc., We have identified a well
      known instrumental technique SEM/SDD-EDS method to identify and estimate the
      waterborne minerals in the scalp hair cuticle in a non-destructive way. Materials
      and Methods: Identify volunteers of urban and rural folks using treated or
      untreated water for their routine hair wash at least for two consecutive years
      and examine their scalp hair cuticle using SEM/SDD- EDS. Results: Water borne
      minerals calcium and aluminium pick up were distinctly identified in the scalp
      hair cuticle as reflected by the quality of water used in urban and rural set up.
      Further restoration of lipid layer through prior application of coconut oil and
      or usage of conditioners prevents calcium pick up. Thereby, SEM/SDD-EDS is one of
      the suitable techniques to estimate the concentration of waterborne minerals in
      the scalp hair cuticle.

PMID- 30221133
TI  - Pathological Changes in Experimental Intramammary Infection with Different
      Staphylococcus Species in Mice.
AB  - Introduction: Mastitis is caused by different Staphylococcus species, produce
      great economic loss to farmers. Present study was conducted to know pathological
      changes in mice inoculated with Staphylococcus epidermidis, S. chromogenes, S.
      haemolyticus and S. aureus isolated from bovine milk. Materials and Methods: Mice
      were inoculated with 50 MUl (2x104 cfu organisms) per mammary gland and
      euthanized at 6, 12, 24, 48, 72 and 96 h. Mammary gland weight, gross and
      histopathological changes of mammary gland, liver, kidney, spleen, heart, lung
      and inguinal lymph node were studied. Results: Mammary gland weight and
      percentage of body weight increased at 6 and 96 h in S. aureus and S.
      haemolyticus infected mice. Gross changes were observed in mammary gland but not
      in other organs. Mammary gland revealed gross changes from 24 to 72 h in three
      Coagulase negative staphylococcal (CNS) species and persisted up to 96 h in S.
      aureus infected mice. Histopathological changes in mammary glands was severe in
      S. aureus and moderate in CNS species. S. aureus infected mice revealed severe
      damage to alveoli and loss of alveolar architecture at 96 h but three CNS species
      infection was overcome by host factors which was evident by proliferation of
      alveolar epithelial cells. No histological changes were observed in kidney,
      spleen, lung, heart and inguinal lymph nodes. Conclusions: S. aureus caused
      severe mastitis in mice when compared to CNS species. Further, it is first report
      of mice to study CNS mastitis, and in future it can be used as model for CNS
      mastitis.

PMID- 30221134
TI  - Ultrastructure Based Morphofunctional Variation of Olfactory Crypt Neuron in a
      Monomorphic Protogynous Hermaphrodite Mudskipper (Gobiidae: Oxudercinae)
      (Pseudapocryptes lanceolatus [Bloch and Schneider]).
AB  - Pseudapocryptes lanceolatus (Bloch and Schneider) is a monomorphic protogynous
      hermaphrodite teleost that possesses ovotestis as gonadal unit of reproductive
      structure. At the onset of breeding season (i.e., June-July), the ovarian tissue
      is gradually differentiating into female-phased P. lanceolatus. At the same time,
      the pear-shaped crypt cells (a type of neuron) are frequently appeared at apical
      part of pseudostratified olfactory neuroepithelium of P. lanceolatus. The crypt
      neuron is characterized by the presence of sunken cilia and microvilli at the
      proximal region. The features of subcellular organelles are also explored in lieu
      of their probable functional significance. The nucleoplasm of mature crypt neuron
      shows chromatin granules having diameter: 15-25 nm. This cell undergoes neural
      apoptosis at the end of breeding phase (i.e., October-November). Fragmented
      chromatin fibers with numerous chromatin granules (diameter: 25-30 nm) in
      nucleoplasm and lysosomal diversity are the most notable characters of apoptotic
      crypt neuron. The large accumulation of heterochromatin chromatins in nucleoplasm
      is also marked under fluorescence microscope. The frequent presence of
      acetylcholinesterase-positive vesicles in axoplasm of crypt neurons is also a
      prime subcellular indicator for inhibition of neural transmission of olfactory
      signals. Therefore, it is concluded that the sex differentiation in P.
      lanceolatus and occurrence of crypt neuron in olfactory neuroepithelium are
      interrelated events during the reproductive period. Consequently, we hypothesized
      that the crypt neuron plays an active role in the implementation of unique
      reproductive strategy through recognition of pheromonal cues within the social
      organization of P. lanceolatus.

PMID- 30221135
TI  - The Ameliorating Effect of Sodium Selenite on the Histological Changes and
      Expression of Caspase-3 in the Testis of Monosodium Glutamate-Treated Rats: Light
      and Electron Microscopic Study.
AB  - Monosodium glutamate (MSG) is a commonly used flavor enhancer that may contribute
      to male infertility. Sodium selenite is inorganic chemical form of selenium (Se).
      Se is best known as an antioxidant. This study was designed to investigate the
      possible ameliorating role of sodium selenite against MSG-induced testicular
      toxicity and histological changes. Forty male albino rats were allocated into
      four groups. Control group received distilled water, SE group received sodium
      selenite (0.25 mg/kg/day) dissolved in distilled water orally, MSG group received
      MSG (6 mg/g/day) dissolved in distilled water orally, and MSG + SE group received
      both MSG and sodium selenite for 45 days. Testicular samples were prepared for
      biochemical, light, and electron microscopic studies. Immunohistochemical
      staining for caspase-3 was done. MSG group demonstrated a significant increase in
      malondialdehyde level, marked damage of seminiferous tubules with a significant
      reduction in diameter and height of the lining epithelium. Spermatogenic cells
      showed disorganization, dark nuclei, reduction in number, and maturation arrest.
      Vacuolations of interstitial tissue and Leydig cells were also observed. Percent
      area of fibrosis and caspase-3 immunoexpression was significantly increased.
      Ultrastructurally, irregular tubular basement membrane and damaged germ cells
      were found. The spermatogenic, Sertoli, and Leydig cells showed irregular
      shrunken nuclei, cytoplasmic vacuolations, and swollen mitochondria. MSG + SE
      group showed much better histological and ultrastructural picture and improvement
      of the measured biochemical and morphometric parameters. Percent area of caspase
      3 immunoexpression was significantly decreased. In conclusion, sodium selenite
      ameliorated the testicular damaging effect of MSG through reduction of oxidative
      stress and apoptosis.

PMID- 30221136
TI  - Histological Effects of Gold Nanoparticles on the Lung Tissue of Adult Male
      Albino Rats.
AB  - Short Introduction: Nanoparticles (NPs) represent a new line in the
      investigations and treatment of group of diseases. Furthermore, it is found in
      many products and enters the body by different roots as ingestion and inhalation.
      Lung is more liable to exposure to these particles. Safety of these particles on
      the lung needs to be examined. Aim of the Work: To study the effect of gold NPs
      (GNPs) on the histological structure of the lung tissue. Materials and Methods:
      Thirty-six healthy male albino rats were randomly divided into three groups
      including control group (Group I) and two GNP-treated groups (Group II received
      low dose and Group III received high dose daily for 14 days). At the end of the
      experiment, all the rats were sacrificed; lungs were dissected and processed to
      be examined by light and electron microscopy. Results: GNPs induced inflammatory
      infiltration dilatation and congestion of the blood vessels in association with
      the collapse of lung alveoli and extravasations of red blood cells. Caspase-3
      immunohistochemical reaction showed strong positive reaction in Group III mainly.
      Ultrastructure observation revealed affection of type II pneumocyte and
      thickening in the alveolar wall. Conclusions: GNPs led to histological changes in
      the lung tissue.

PMID- 30221138
TI  - Salivary Sheaths of the Asian Citrus Psyllid Show Signs of Degradation 3-4 Weeks
      Following Their Deposition into Citrus Leaves by the Feeding Psyllids.
AB  - Background: Salivary sheaths, also known as stylet sheaths or stylet tracks, are
      essential features of the piercing-sucking feeding mechanism of plant-feeding
      hemipteran insects, many of which are vectors of economically important plant
      viral and bacterial pathogens. Although knowledge of their structure and function
      is incomplete, these salivary sheaths are frequently used by researchers to study
      hemipteran's feeding behavior, host preference, or host resistance, because these
      sheaths remain in the plant tissues after the insect withdraws its stylets
      following its feeding or probing on these tissues. However, in most cases, it is
      not known how long these salivary sheaths may last in plant tissues after their
      deposition by the feeding insects. An earlier report suggested that the salivary
      sheaths of the Asian citrus psyllid, Diaphorina citri (Hemiptera, Liviidae),
      vector of the devastating huanglongbing (citrus greening) disease bacterium,
      start to dissipate 1 week after their deposition in citrus leaves. Methods and
      Results: Here, using epifluorescence microscopy of cross sections in citron
      leaves, we found that D. citri salivary sheaths show signs of degradation in 3-4
      weeks and become mostly degraded by 5-6 weeks, following their deposition by the
      psyllids into citrus tissues. Degradation of the salivary sheath starts at or
      near the "flange" area close to the leaf surface and continues gradually inward
      through the intercellular part of the sheath, within the mesophyll tissue, but
      apparently does not extend to the deeper or intracellular parts of the sheath in
      or near the phloem. Staining citron leaf sections with the fluorescent stain
      calcofluor white, which stains fungi, or propidium iodide (DNA/RNA stain)
      suggested that the degraded parts of the older salivary sheaths are not
      associated with fungi or bacterial accumulations. Conclusion: We speculate that
      degradation of the salivary sheaths may be due to enzymatic activities in the
      host plant, especially in the extracellular matrix of the mesophyll tissue.

PMID- 30221137
TI  - Extracellular Matrix Remodeling in Human Disease.
AB  - The extracellular matrix (ECM) is a meshwork of proteins and carbohydrates that
      supports many biological structures and processes, from tissue development and
      elasticity to preserve the structures of entire organs. In each organ, the
      composition of the ECM is distinct. It is a remarkably active three-dimensional
      structure that is continuously undergoing remodeling to regulate tissue
      homeostasis. This review aims to explain the role of ECM proteins in the
      remodeling process in different types of disease. The hardening of the ECM
      (desmoplasia), as well as its manipulation, induction, and impairment in
      regulation of its composition can play a role in several diseases, examples of
      which are chronic obstructive pulmonary disease, pancreatic ductal
      adenocarcinoma, spinal cord injury, progression and metastasis of breast cancer,
      and neurodegenerative condition in the brain such as Alzheimer's disease.
      Remodeling is also associated with diet-induced insulin resistance in many
      metabolic tissues. A greater comprehension of the way in which the ECM regulates
      organ structure and function and of how ECM remodeling affects the development of
      diseases may lead to the improvement and discovery of new treatments.

PMID- 30221139
TI  - Ameliorative Influence of Ajwa Dates on Ochratoxin A-Induced Testis Toxicity.
AB  - Ajwa dates (Phoenix dactylifera), cultivated particularly in Al-Madina Al
      Monawarh in Saudi Arabia, and considered as a rich source of natural antioxidants
      such as anthocyanins, carotenoids and phenolics. It is believed that Ajwa dates
      have a wide range of protective effects. For this reason, this work aimed to
      investigate the ameliorative effect of Ajwa dates aqueous extract against
      ochratoxin A (OTA)-induced testicular lesions in rats. Rats were divided into
      four groups and treated for 28 days. Group I served as normal control, group II
      (OTA exposed) treated orally with 289 MUg/kg/day. Group III (Ajwa dates aqueous
      extract) treated orally with 1 g/kg/day. The last group served as the protective
      group (pretreated with Ajwa dates extract, then OTA). Histological studies
      revealed that OTA induced lesions in the testicular structure included
      proliferation of sertoli cells, impairment of some spermatogenesis stages and
      accumulation of premeiotic germinal cells. However, pretreatment with Ajwa dates
      extract prevented all the testicular damage and improved spermatogenesis, as well
      as remarkably enhanced the testicular structure. In conclusion, Ajwa dates
      aqueous extract has a powerful protective effect and ameliorative influence
      against OTA- induced testicular damage and may be used to treat sexual impairment
      and male infertility.

PMID- 30221141
TI  - Assessment of the Possibility of Identification of Black Toners on Printouts in
      Lexmark Printers Using SEM Method.
AB  - Background: Document examiners are frequently asked to determine whether or not a
      printout has originated from a particular laser printer. The printer can rarely
      be identified unless some unique defects or irregularities of the printer are
      present on the printout. Aim/Objective: The project aimed at obtaining the
      individual identification of printing and copying devices. Material and Methods:
      This paper presents an overview of a systematic approach to characterizing and
      discriminating the toner of different laser printer cartridges using scanning
      electron microscopy. A total of 21 collected printouts were printed on 21
      different Lexmark printing machine models. Sixteen printouts were obtained using
      printers with original toner cartridges, while five printouts were obtained using
      printers with replacements. Clear criteria were established for individual
      assessment. Results: Based on the SEM images and established criteria, the
      details of topography of the toner structure were revealed. Based on this study,
      the differences or similarities of toners on tested printouts were determined.
      Conclusion: The SEM technique can be successfully, simply, and rapidly applied to
      the analysis of toners on paper documents.

PMID- 30221140
TI  - More Than an Association: Latent Toxoplasmosis Might Provoke a Local Oxidative
      Stress That Triggers the Development of Bipolar Disorder.
AB  - Introduction: Toxoplasma gondii, a common parasitic infection, has a special
      affinity to the brain. It has a lifelong existence without an apparent clinical
      disease. While the etiology of bipolar disorder (BD) remains unclear,
      epidemiological studies suggest a role for infections. Central nervous system is
      particularly susceptible to oxidative stress (OS) because of its high metabolic
      rate and its low levels of antioxidant defenses. OS is a contributor to the
      initiation and progression of many neurological illnesses. OS injury is a
      constantly and compelling finding associated with BD and toxoplasmosis. Aim: This
      cross-sectional study has investigated a possible role of toxoplasma-induced OS
      in the development of BD. Methods: Healthy controls and BD patients were examined
      for anti-Toxoplasma immunoglobulin-G (IgG) and two protein (3-nitrotyrosine) and
      DNA (8-hydroxy-2' deoxyguanosine [8-OHdG]) OS markers. Results: Toxoplasma
      positivity was higher (40%) among BD patients compared to controls (12%).
      Significantly higher levels of anti-Toxoplasma IgG were detected in BD patients
      compared to controls. Nitrotyrosine (796.7 +/- 106.28) and especially 8-OHdG
      (20.31 +/- 8.38) were significantly higher among toxo-positive BD compared to
      toxo-negative BD (675.97 +/- 144.19 and 7.44 +/- 2.86) and healthy controls
      (464.02 +/- 134.6 and 4.17 +/- 1.43). Conclusion: These findings might indicate a
      role for Toxoplasma infection in the development of BD, possibly through creating
      a highly oxidative brain environment.

PMID- 30221142
TI  - Enamel Surface Morphology: An Ultrastructural Comparative Study of Anterior and
      Posterior Permanent Teeth.
AB  - Introduction: Enamel is one of the most important structures of the tooth, both
      functionally and aesthetically. Because of the highly mineralized nature of
      enamel, its structure is difficult to study under routine light microscopy. Since
      scanning electron microscopy (SEM) offers the possibility of studying structures
      under very high magnification without altering the gross specimen, it is one of
      the best methods to study the enamel surface. Aims and Objectives: To study and
      compare the surface morphology and morphometry of enamel on various surfaces of
      permanent dentition. Materials and Methods: A total of 20 permanent teeth were
      analyzed under the SEM. In both anterior and posterior teeth, four surfaces -
      mesial, distal, labial, and lingual - in three thirds - cervical, middle, and
      incisal - were studied. In addition, the occlusal surface was also studied for
      the posterior teeth. The different prism morphology and prism dimensions were
      recorded. Results: Based on our observations, we could definitely identify striae
      of retzius, debris, and cracks under *50 magnification. Three morphological
      patterns of prism arrangement were identified: Type 1 - shallow prisms, Type 2 -
      well-defined prisms, Type 3 - microporosities, on analyzing the mesial, distal,
      labial, lingual, and occlusal surfaces of the permanent teeth, at *3000
      magnification. The prisms were measured under *6000 magnification and the results
      showed larger prisms in posterior than in anterior teeth. Conclusion: The study
      aided us in categorizing the enamel prism structure based on morphology and
      morphometry in anterior and posterior teeth of the permanent dentition.

PMID- 30221144
TI  - Claiming control: cooperation with return as a condition for social benefits in
      Austria and the Netherlands.
AB  - Theoretically embedded in the migration/social policy nexus, this paper
      investigates cooperation with return (CWR) as a policy tool to remove practical
      deportation barriers for third-country nationals pending removal. Based on legal
      and policy documents and expert interviews with stakeholders in Austria and the
      Netherlands, the paper asks how CWR is implemented and what influence it has,
      both on migration control aims and on access to social rights. We argue that the
      politicization of the issue and diverging interests between policy networks of
      welfare and migration affect the regulation and implementation of the tool. By
      comparing the use of CWR within two country contexts, the analysis presented here
      adds valuable insights on features of governmental instruments in response to the
      "deportation gap". The paper further adds to the literature on sanction-oriented,
      personalized migration policies.

PMID- 30221143
TI  - Presence of Multidrug-Resistant Bacteria on Mobile Phones of Healthcare Workers
      Accelerates the Spread of Nosocomial Infection and Regarded as a Threat to Public
      Health in Bangladesh.
AB  - Recently, mobile phones have become a potent vector for the transmission of
      pathogens. In hospitals, the use of the mobile phones by healthcare workers in an
      unhygienic manner accelerates the spread of nosocomial infection. We aimed to
      investigate the prevalence of microbiological contamination of mobile phones
      belonging to clinicians in Bangladesh hospitals. From 100 samples, we identified
      69 isolates of bacteria including 22 Staphylococcus aureus; 11 Pseudomonas
      aeruginosa; 14 Escherichia coli; 6 Salmonella typhi 6 and 16 Staphylococcus
      epidermidis. On the basis of antibiotic susceptibility test using 11 antibiotics,
      it has been observed that most of the isolated bacteria became resistant to
      antibiotics and compared to other isolates, isolates of S. epidermidis and S.
      typhi were more resistant and sensitive, respectively. About 68.8% isolates
      showed that their resistance capacities against ampicillin but in contrast, 56.6%
      isolated were susceptible to imipenem. Azithromycin and imipenem against S.
      aureus, gentamicin against P. aeruginosa, tetracycline and imipenem against E.
      coli, tetracycline against S. typhi, and S. epidermidis revealed significant
      antimicrobial affectivity. We found that mobile phones are potential vectors to
      spread antibiotic-resistant nosocomial pathogens. Based on the study, an
      effective disinfection practice for cellular phones used in hospitals should be
      introduced to prevent the potential of cross-contamination.

PMID- 30221145
TI  - Matrix metalloproteinase (MMP) and immunosuppressive biomarker profiles of seven
      head and neck squamous cell carcinoma (HNSCC) cell lines.
AB  - Background: Biomarkers like programmed death ligand-1 (PDL1) have become a focal
      point for immunotherapeutic checkpoint inhibition in head and neck squamous cell
      carcinoma (HNSCC). However, it's only part of the total immunosuppressive
      biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes
      that break down the basement membrane allowing cancer cells to metastasize and
      play an important role in the tumor microenvironment. MMPs can also activate
      certain cytokines, growth factors, and chemokines post-translationally. The
      objective of this study was to determine MMP and biomarker profiles of seven
      different HNSCC cell lines. Methods: Authenticated cell lines were grown in
      minimal media at 1*106 viable cells/mL and incubated at 37  degrees C. After 24
      hrs supernatants were collected, and adhering cells were lysed. Multiplex
      immunoassays were used to determine MMP1, MMP7, MMP9, IL-6, VEGFA, IL-1alpha, TNF
      alpha, GM-CSF, IL-1RA, and IL-8 concentrations in supernatants. ELISAs were used
      to determine PDL1, CD47, FASL, and IDO concentrations in cell lysates. A one-way
      ANOVA was fit to examine log-transformed concentrations of biomarkers between
      seven HNSCC cell lines, and pairwise group comparisons were conducted using post-
      hoc Tukey's honest significance test (alpha=0.05). Results: Significant
      differences (P<0.05) in MMP and biomarker concentrations were found between the
      seven HNSCC cell lines. For example, MMP9 was highest in SCC25 and UM-SCC99, MMP7
      was highest in SCC25 and UM-SCC19, and MMP1 was highest in SCC25. Conclusions:
      These results suggest different patients' HNSCC cells can express distinct
      profiles of select biomarkers and MMPs, which could be due to metastatic stage of
      the cancer, primary tumor site, type of tissue the tumor originated from, or
      genomic differences between patients. MMP and biomarker expression profiles
      should be considered when choosing cell lines for future studies. The results
      support the reason for personalized medicine and the need to further investigate
      how it can be used to treat HNSCC.

PMID- 30221146
TI  - The Management of Inflammatory Bowel Disease in Elderly: Current Evidence and
      Future Perspectives.
AB  - Data on the elderly population with inflammatory bowel disease (IBD) are scarce,
      as this population is normally excluded from clinical trials. With an ageing
      population and an overall increasing prevalence of IBD; the incidence of IBD in
      elderly is rising. Comorbidities, wide differential diagnosis and polypharmacy
      make the diagnosis and management of the disease in elderly more challenging
      compared to that in younger adults. The knowledge of specific requirements for
      the management and treatment of IBD in advanced age may help in the framing of
      the definition of the appropriate care of this patient group. This manuscript
      reviews the most recent knowledge in the epidemiology, diagnosis and management
      of IBD in this population.

PMID- 30221147
TI  - High Prevalence of Vitamin D Deficiency among Patients with Inflammatory Bowel
      Disease.
AB  - Background: Vitamin D is a hormone with immunomodulatory properties. Vitamin D
      deficiency has been reported for patients with inflammatory bowel disease (IBD).
      In this cross-sectional study, 25-hydroxyvitamin D3 (25-OH-D3) levels in patients
      with IBD were compared to those in patients with irritable bowel syndrome (IBS).
      Methods: A total of 181 patients, 156 with IBD and 25 with IBS, were included.
      The influence of disease activity, inflammatory markers, physical activity, and
      season were assessed. Results: A total of 58.6$ (n = 58) of the patients with
      Crohn's disease (CD) and 44.6$ (n = 25) of the patients with ulcerative colitis
      (UC) had a 25-OH-D3 level < 50 nmol/L. CD patients showed significantly decreased
      25-OH-D3 levels compared to the IBS patients (p = 0.018), but no significant
      difference was found for UC patients. In a linear regression model adjusted for
      age, gender, and BMI, a significant inverse association of C-reactive protein
      (CRP) (p = 0.031) and faecal calprotectin (FC) (p = 0.025) with 25-OH-D3 levels
      was observed for CD patients. Seasonal variation in 25-OH-D3 levels was found in
      CD patients, with significantly lower values in spring than in summer (p = 0.04).
      Conclusion: Vitamin D deficiency was common in all IBD patients, but more
      pronounced in CD patients, in whom it also showed a significant inverse
      association with inflammatory markers such as CRP and FC.

PMID- 30221148
TI  - Eribulin Does Not Prevent Epithelial-to-Mesenchymal Transition in HT-29
      Intestinal Epithelial Cells.
AB  - Background: Fistula formation affects up to 50$ of Crohn's disease (CD) patients
      and causes considerable morbidity. Current pharmacological management mainly
      includes antibiotics, immunosuppressives, and anti-TNF antibodies. CD fistulas
      develop from intestinal epithelial cells undergoing epithelial-to-mesenchymal
      transition (EMT). TGFbeta, the most important inducer of EMT, is detectable
      around CD fistula tracts and induces expression of the EMT-associated
      transcription factors SNAIL1 and SLUG as well as of IL-13. Conversely, together
      with TNF, IL-13 induces the expression of the transcription factor Ets-1 and
      beta6-integrin, which are associated with cell invasiveness. Eribulin is a
      synthetic derivative of halichondrin B, a large polyether macrolide, which
      reverses EMT in triple-negative breast cancer (TNBC) cells. Here, we investigated
      whether Eribulin might be a potential therapeutic option for CD fistulas via the
      inhibition of EMT. Summary: Chronic treatment with high concentrations of
      Eribulin (> 5 ng/ml) is toxic for intestinal epithelial cells (IEC), and Eribulin
      treatment does not decrease the mRNA expression of EMT markers in HT-29
      monolayers nor prevent EMT in HT-29 spheroids. Together with TNF, Eribulin
      induces the expression of vimentin and SLUG mRNA in HT-29 spheroids but
      concomitantly also promotes E-cadherin expression. Key Messages: Our data suggest
      that the previously reported antimetastatic effect of Eribulin in TNBC by
      reversing EMT does not apply to IEC. Interestingly, Eribulin promotes E-cadherin
      expression, suggesting an additional mechanism. The increase of E-cadherin might
      point towards the described role for Eribulin in reversing EMT. Taken together,
      our data do not support a role for Eribulin as treatment option for CD-associated
      fistulas.

PMID- 30221149
TI  - Treatment of Active Crohn's Disease with Exclusive and Partial Enteral Nutrition:
      A Pilot Study in Adults.
AB  - Background and Aim: Enteral nutrition (EN) is not commonly used for the treatment
      of adults with active Crohn's disease (CD), despite patient interest in nutrition
      based alternatives to corticosteroids and evidence of efficacy in paediatric CD.
      The aim of this study was to assess the impact of 2 different EN regimens on
      disease symptoms, nutrition and inflammatory markers in young adults with active
      CD. Methods: A prospective non-randomized pilot study of adults aged 16-40 years
      with active CD on endoscopy or imaging was undertaken. Patients were sequentially
      recruited to use 2 weeks of exclusive EN (EEN) followed by either 6 weeks of EEN
      or partial EN (PEN) with usual diet. Assessments of disease symptoms, nutrition
      and inflammatory markers were undertaken at baseline and throughout the
      treatment. Results: Thirty-eight patients with active disease were recruited.
      Thirty-two (84$) patients completed 2 weeks of EEN and had significant
      improvements in disease symptoms (p = 0.003), serum c-reactive protein (CRP; p =
      0.005), insulin-like growth factor-1 (p = 0.006) and faecal calprotectin (FC; p =
      0.028). During the following 6 weeks, 21 patients continued EEN (14 [67$]
      completed treatment) and 11 patients used PEN (9 [82$] completed treatment).
      Initial improvements in symptoms, CRP and nutrition markers were sustained over
      the next 6 weeks on both treatments. FC non-significantly increased in 5 out of 9
      patients who used PEN and at week 8 FC was greater than 500 ug/g in 9 out of 14
      and 7 out of 9 patients who used exclusive or PEN respectively. There was no
      significant difference in clinical outcomes between the 2 groups at week 8.
      Conclusion: Two weeks of EEN significantly improved disease symptoms, nutrition
      and inflammatory markers. Further treatment with exclusive or PEN maintained
      initial improvements.

PMID- 30221150
TI  - Efficacy and Safety of Dose Escalation to Adalimumab 80 mg Every Other Week in
      Japanese Patients with Crohn's Disease Who Lost Response to Maintenance Therapy.
AB  - Background: Dose escalation is often recommended for loss of response in anti
      TNFalpha-treated patients with Crohn's disease (CD). This 52-week phase 3,
      multicenter study investigated the efficacy and safety of escalation to
      adalimumab 80 mg every other week (EOW) in Japanese patients with CD who lost
      response to maintenance adalimumab 40 mg EOW. Methods: Twenty-eight patients aged
      >=15 years with moderately to severely active CD who had previously attained and
      subsequently lost clinical response to maintenance ada limumab received open
      label adalimumab 80 mg EOW during weeks 0-50. Loss of response was defined as CD
      activity index (CDAI) >=200, increases in CDAI >=50 from minimum observed value,
      and C-reactive protein (CRP) >=1 mg/dL at screening. The primary endpoint was the
      proportion of patients achieving a CDAI decrease >=50 (CR-50) from baseline at
      week 8. Results: At weeks 8 and 52, 75.0 and 57.1$ of patients achieved CR-50 and
      25.0 and 35.7$ achieved clinical remission (CDAI < 150), respectively; median CRP
      changes from baseline were -0.39 and -0.77 mg/dL, respectively. Most treatment
      emergent adverse events were mild to moderate. Conclusions: Adalimumab dose
      escalation to 80 mg EOW improved CD activity in patients who had lost response to
      maintenance adalimumab, with no new safety signals. (ClinicalTrials.gov
      Identifier: NCT01958827.).

PMID- 30221151
TI  - Survival after resection of colorectal liver metastases in octogenarians and
      sexagenarians compared to their respective age-matched national population.
AB  - Background: The aim of the current study was to investigate survival after
      resection of colorectal liver metastases (CLM) in octogenarians. The survival of
      octogenarian patients was compared to the survival of the national population of
      octogenarians and the survival of sexagenarians, the latter representing the
      average-age patient undergoing resection of CLM. Methods: Octogenarian and
      sexagenarian were defined as person 80-89 and 60-69 years of age, respectively.
      Survival analyses of patients who underwent resection of CLM between 2002 and
      2014 were performed. Data from Statistics Norway were used to estimate the
      survival of the age-matched national population of octogenarians (ageM-Octo) and
      the age-matched national population of sexagenarians (ageM-Sexa). Results: During
      the study period, 59 octogenarians underwent resection of CLM. The majority of
      patients underwent a minor liver resection (n=50). In octogenarians, the 5-year
      survival was 32.5% and 66.3% [difference, 33.8 percentage points (pp)] in
      patients and ageM-Octo, respectively. The 10-year survival was 14.1% and 31.2%
      (difference, 17.1 pp) in patients and ageM-Octo, respectively. In sexagenarians,
      the 5-year survival was 50.9% and 96.2% (difference, 45.3 pp) in patients and
      ageM-Sexa, respectively. The 10-year survival was 35.7% and 90.3% (difference,
      54.6 pp) in patients and ageM-Sexa, respectively. The 5-year cancer-specific
      survival and 5-year recurrence-free survival (RFS) after resection of CLM in
      octogenarians were 43.1% and 32.9%, respectively. Conclusions: After resection of
      CLM, the survival was poorer in octogenarians than in sexagenarians. However, the
      difference between the survival curves of patients and their age-matched
      population was smaller in octogenarians. In practice, this finding may indicate a
      greater benefit of resection in the elderly than the survival rates alone would
      suggest.

PMID- 30221152
TI  - Synchronous colorectal liver metastases: a national survey of surgeon opinions on
      simultaneous resection and multidisciplinary cooperation.
AB  - Background: The management of patients with synchronous colorectal liver
      metastases (sCRLM) has evolved significantly (improved chemotherapy, hepatic
      surgery advancements, colonic stenting, consultation synergies). We sought to
      better understand surgeon viewpoints on optimal referral patterns and the
      delivery of simultaneous resections. Methods: A 40 question on-line survey was
      offered to members of the Canadian surgical community. Statistical analysis was
      descriptive. Results: A total of 52 surgeons responded. Most colorectal surgeons
      (CRS) had access to and a good working relationship with regional hepatobiliary
      (HPB) surgeons (86%) and medical oncologists (100%). The majority (92%) believed
      there was a role for simultaneous resection of sCRLM, with 69% having first hand
      experience. Many CRS (62%) discussed all cases of known hepatic metastases with
      HPB prior to any resection. When a lesion was asymptomatic/minimally symptomatic,
      most CRS (92%) discussed them with medical oncology/HPB prior to resection (8%).
      Bilobar metastases (58%), patient comorbidities (35%), portal lymphadenopathy
      (35%), and patient age (15%) restricted CRS from obtaining HPB consultations.
      Many CRS (46%) did not believe that resecting hepatic metastases prior to the
      primary lesion might be beneficial. Most CRS (60%) reported they could not
      accurately predict hepatic resectability, with only 27% familiarity with evidence
      based guidelines. Despite working in smaller hospitals with less access to HPB
      and less experience with simultaneous resections, non-CR general surgeons more
      commonly supported a 'liver-first' approach. Conclusions: There was general
      agreement between CRS and general surgeons on numerous topics, but additional
      education is required with regard to HPB surgical capabilities and to provide
      truly individualized patient-centered care.

PMID- 30221153
TI  - Effectiveness of additional resection of the invasive cancer-positive proximal
      bile duct margin in cases of hilar cholangiocarcinoma.
AB  - Background: The survival benefits of additional resection of the positive
      proximal ductal margin (PM) in hilar cholangiocarcinoma (HCCA) remains
      controversial. This retrospective study investigated the effectiveness of
      additional resection of the invasive cancer PM under different levels of
      preoperative carbohydrate antigen 19-9 (CA19-9). Methods: Patients who underwent
      hepatectomy for HCCA from 2000 to 2017 were analyzed. Surgical variables,
      resection margin status, length of the PM (LPM), prognostic factors, and survival
      were evaluated. Results: A total of 228 patients were enrolled: 175 PM(-) without
      additional resection patients (group A), 21 PM(-) after additional resection
      (group B), 16 PM(+) without additional resection (group C), and 16 PM(+) after
      additional resection (group D). The median survival of group B (20.99 months) was
      similar to that of group A (23.00 months; P=0.16), and both were significantly
      better than those of group C (11.60 months) and D (9.50 months), especially when
      preoperative CA19-9>150 U/mL (P<0.05). The survival of patients with an LPM >10
      mm was significantly better compared with those with an LPM <=10 mm, especially
      when preoperative CA19-9 was >150 U/mL (P<0.05). Only in the LPM >10 mm group,
      the survival of group B was comparable with that of group A (P>0.05).
      Conclusions: HCCA patients could get a survival benefit from a negative PM
      resulting from additional resection. Survival could be comparable with that of
      negative PM without additional resection among HCCA patients. An LPM >10 mm is
      possibly more associated with better survival compared with whether additional
      resection of the positive PM is performed under different levels of preoperative
      CA19-9.

PMID- 30221154
TI  - Cohort contributions to trends in the incidence and mortality of intrahepatic
      cholangiocarcinoma.
AB  - Background: The incidence and mortality of intrahepatic cholangiocarcinoma (ICC)
      are increasing worldwide. We used age-period-cohort (APC) modeling to evaluate
      the contribution of cohort effects to trends in ICC incidence and mortality in
      the US. Methods: Incidence data were acquired from the Surveillance, Epidemiology
      and End-Results (SEER) program. Mortality data were obtained from the Centers for
      Disease Control and Prevention WONDER Database. APC models using restricted cubic
      splines were fitted to estimate change in incidence and mortality risk over age,
      and modification of incidence and mortality risks according to birth cohort and
      period of diagnosis or death. Likelihood ratio tests were used to summarize
      improvement in model fit with APC modeling. Results: There were 4,053 cases of
      ICC at SEER registry sites between 1973-2012. ICC incidence increased with older
      age and across all birth cohorts examined. Inclusion of cohort effects tended to
      improve model fit relative to an age-period model (likelihood ratio test
      P=0.082). The national crude ICC-related mortality rate increased from 2.9 to 5.0
      per 100,000 among males and 2.7 to 4.6 per 100,000 among females. Among males,
      ICC mortality risk varied across birth cohorts, and inclusion of cohort effects
      in a model predicting ICC mortality risk improved model fit (likelihood ratio
      test P=0.001), but cohort effects did not alter model fit among females
      (P=0.223). Conclusions: ICC incidence and mortality have increased over time in
      the United States. Birth cohort effects influenced increased ICC incidence and
      ICC mortality among males, but were not evident in the trend of ICC mortality
      among females.

PMID- 30221156
TI  - Neoadjuvant therapy for pancreatic ductal adenocarcinoma-real effects or patient
      selection?

PMID- 30221155
TI  - Laparoscopic liver resection: a review of current indications and surgical
      techniques.
AB  - Laparoscopic liver resection (LLR) has been the most impressive development in
      the field of liver surgery in recent two decades. Technical innovations and
      experience accumulation have made LLR a safe and effective procedure with faster
      postoperative recovery. Despite the fast spreading of the procedure, details
      regarding the indications, oncological outcomes and technical essentials were
      still disputable. To address these issues, two international consensus
      conferences were hold to update the knowledge in this field. The statements of
      the both conferences were not conclusive and more high-quality researches are
      required. In this article, we reviewed the development and the current state of
      LLR. Indications, outcomes, surgical techniques and devices used in LLR were also
      discussed.

PMID- 30221157
TI  - Will the magnetic resonance imaging proton density fat fraction replace liver
      biopsy as the gold standard for detecting steatosis?

PMID- 30221158
TI  - Efficacy of radiofrequency ablation of hepatocellular carcinoma prior to liver
      transplantation and the need for competing-risk analysis.

PMID- 30221159
TI  - Searching for common ground in a global disease.

PMID- 30221161
TI  - Percutaneous ablation for HCC eligible to transplantation: providing more
      opportunities of remission in the context of graft shortage.

PMID- 30221160
TI  - Liver resection for hepatocellular carcinoma associated with hepatic vein
      invasion: is it time to reconsider the current treatment guidelines?

PMID- 30221162
TI  - Chronic non-communicable disease risks presented by lipid oxidation products in
      fried foods.

PMID- 30221163
TI  - Complete portal vein occlusion after cyanoacrylate sclerotherapy in biliary
      atresia treated by living donor liver transplantation with intraoperative portal
      vein stenting via segment 4 portal vein stump.

PMID- 30221164
TI  - Adenosquamous carcinoma arising in a duplication cyst of the gallbladder.

PMID- 30221165
TI  - True technology-enabled mental health care: trust, agency and ageing.

PMID- 30221166
TI  - Smartphone ownership and perspectives on health apps among a vulnerable
      population in East Harlem, New York.
AB  - Background: Individuals from low-income and racial/ethnic minority backgrounds
      have traditionally had less access to mobile health (mHealth) technologies, but
      there is evidence that this gap has been rapidly narrowing. Given the increase in
      access to mobile technologies recently seen in vulnerable populations, mHealth
      has been championed as a strategy for improving population health and reducing
      health disparities. However, members of low-income and racial/ethnic minority
      populations have had a limited role in the development and implementation of
      mHealth interventions designed to impact them. Methods: We used community-based
      participatory research (CBPR), a research approach that is frequently employed to
      help reach communities that are disproportionately affected by illness but are
      difficult to engage. Our community-academic collaboration, the East Harlem
      Partnership for Diabetes Prevention, sought to create a mobile technology
      platform that would allow adults in East Harlem, New York to improve their own
      health and promote the health of the broader community. As a first step, we
      developed and conducted a survey of community residents to better understand
      access to, usage of, and attitudes towards mobile technologies among diverse, low
      income adults. We administered the cross-sectional survey to a convenience sample
      of adults who utilized a variety of community-based organizations in East Harlem.
      We examined frequencies for each survey item and then used chi-square tests (or
      Fisher's exact tests) and multivariate logistic regression to evaluate
      relationships between these outcomes and sociodemographic factors. Results: We
      approached 154 people, of whom 104 (68%) agreed to participate. The majority of
      respondents were of Black and/or Hispanic/Latino descent with a mean age of 37
      years. Our sample displayed a high percentage of smartphone ownership (82% of the
      participants reported that they owned a cell phone, and 88% of owners reported
      that their cell phone was a smartphone). We found lower rates of ownership among
      individuals who were older, self-identified as Latino, insured by Medicare, and
      had a household income of less than $30,000 per year. Multivariate logistic
      regression showed that after adjusting for age, gender and race, those with at
      least a high school education were seven times more likely to use health apps
      than those with less than a high school education (OR 6.8, 95% CI: 1.7-27.1).
      Participants expressed interest in health promoting apps that provide
      interactive, individualized diet, exercise and weight loss tools and offer
      information about local health resources and events. Conclusions: Despite some
      notable disparities, our study results suggest that the digital divide is
      narrowing in the East Harlem community with relatively high rates of smartphone
      ownership and use, even among individuals from low-income, low education
      backgrounds and those without health insurance. Based on study results, our
      partnership developed an app supporting healthy lifestyle and diabetes prevention
      tailored to the East Harlem community.

PMID- 30221167
TI  - Extreme body messages: themes from Facebook posts in extreme fitness and
      nutrition online support groups.
AB  - Background: Extreme fitness and nutrition programs, that are said to "jump start"
      a healthy lifestyle, are becoming more pervasive. While some research has
      explored the harmful impact of fitspiration, thinspiration, and pro
      anorexia/bulimia websites, no studies have examined the content associated with
      these extreme programs that advertised as promoting a healthy lifestyle. The
      objective of this study was to analyze posts found on extreme fitness and
      nutrition program support pages on Facebook. As these programs have become more
      popular, along with Facebook platforms for their participants, examining online
      user-generated posts related to these programs can provide information about the
      types of messages being promoted, and whether these can contribute to disordered
      eating and other harmful health behaviors. Methods: User data were selected from
      one month from public posts on two popular Facebook fitness groups. Both groups
      were short-term programs that set extreme guidelines for fitness and nutrition.
      Researchers examined the data for harmful health messages using an individual
      coding strategy with inter-rater reliability (Kappa =0.92). Results: Majority
      (88.6%) of messages analyzed promoted harmful health messages. Common categories
      of messages included losing weight/fat, promoting dieting/restraint, and harmful
      body messages, which promoted unsafe ways to attain certain body types.
      Conclusions: The data analyzed in this study represent overwhelmingly negative
      commentary relating to harmful health and body messages. Messages in this study
      normalized dysfunctional behaviors and promoted fixating on certain body parts
      and objectifying bodies. These Facebook groups, though intended to be a sort of
      online support forum, provide an open space for body negativity and promotion of
      extreme behaviors for the sake of thinness. Most concerning, participants of
      these programs, which are advertised as promoting health, are expressing
      unhealthy thoughts and behaviors surrounding food, exercise, and body image.
      Given the ease of accessibility to this content using online platforms, these
      harmful messages can reach large groups of people and continue adding to a
      culture that values physical appearance to the detriment of health.

PMID- 30221168
TI  - Evaluation of the effectiveness of mobile diabetes management system with social
      networking and cognitive behavioural therapy (CBT) for T2D.
AB  - Background: In the Saudi Arabia region there are no previous studies related to
      the use of social networks combined with the management of mobile diabetes. In
      this sense, the aim of this feasibility investigation is to evaluate the
      application and utility of the SANAD system (Saudi Arabia Networking for Aiding
      Diabetes) to support Saudi type 2 diabetes adult patients. Methods: Twenty
      patients from a clinic in Saudi Arabia-Dammam were recruited to use the SANAD
      system. The study design was a randomized controlled trial (RCT) with two groups:
      an intervention group using SANAD system and a control group using conventional
      diabetes treatment. Glycated hemoglobin (HbA1c), diabetes knowledge test (DKT)
      and Self-efficacy Scale (SES) were documented. Results: Nineteen patients
      completed the study. Mean baseline HbA1c (%) was 8.14 (SD 1.20) and decreased to
      7.54 (SD 0.96) after the SANAD intervention process [mean (SEM) decrease 0.600
      (0.102)]. A paired-samples t-test showed this change to be significant (P=0.000).
      Linear regression analyzed each study group separately, and revealed that age
      significantly predicted change in HbA1c (%) in the intervention group, with older
      age (i.e., 41-50 years) associated with higher HbA1c (%) at 6 months, as compared
      with baseline values (beta=0.865, t=3.67, P<0.05). The mean diabetes knowledge
      score prior to the intervention (baseline) was 12.11 (SD 2.09), which rose to
      14.56 (SD 1.59) afterward. This increase [mean (SEM), 2.44 (0.530)] was shown to
      be significant using the paired-samples t-test (P=0.002). Linear regression
      demonstrated that age, gender, and educational level were not related to
      increased diabetes knowledge in each study group. The mean self-efficacy score
      prior to the intervention (baseline) was 5.17 (SD 0.45), which rose to 6.17 (SD
      0.39) afterward. This increase [mean (SEM), 0.944 (0.192)] was shown to be
      significant using the paired-samples t-test (P=0.001). Linear regression
      demonstrated that age, gender, and educational level were not related to
      increased self-efficacy in each study group. Conclusions: This study demonstrates
      that using of SANAD system is acceptable, and feasible in supporting diabetes
      care in Saudi Arabia. This study is the first in Saudi Arabia to demonstrate
      similar benefits of using this technology on social diabetes and management. A
      national clinical trial is needed to assess precise benefits of self-care and
      knowledge.

PMID- 30221169
TI  - Use of adjunct cardiovascular therapy in patients hospitalised for acute
      exacerbations of COPD.
AB  - In real-life practice, acute exacerbation of COPD is often treated as a
      cardiopulmonary syndrome http://ow.ly/uAnk30luMYz.

PMID- 30221170
TI  - Constitutively active SMAD2/3 facilitates efficient transcription factor-mediated
      cell conversion.

PMID- 30221171
TI  - Role of alternative splicing in hematopoietic stem cells during development.

PMID- 30221172
TI  - Regeneration of injured tissue: stem cell dynamics at interplay with mTORC1.

PMID- 30221173
TI  - Non-Mammalian Nuclear Receptors: From Evolution to Human Disease.

PMID- 30221174
TI  - Effect of Increased Amounts of Fe, Zn, and Cd on Uptake, Translocation, and
      Accumulation of Human Health Related Micronutrients in Wheat.
AB  - Agricultural Scientists has lifted the crop production many folds' overs last 100
      years but nutritive quality of crop products has not been addressed accordingly
      as a result humans in many parts of the world are suffering from malnutrition.
      The efficient improvement of nutritive quality of important crop species like
      wheat is dependent on the understanding of the acquisition of micronutrients from
      soil environment and subsequent translocation and distribution into different
      tissues. The objectives of this work were to understand the effect of increased
      concentrations of Fe, Zn, and Cd 1) on overall mineral and metal concentrations,
      2) on acquisition, translocation, and distribution of minerals among different
      tissues, and 3) on the inter-relationship of the minerals and metals as reflected
      in changing the relationship pattern in wheat. The application of increased
      concentrations of Fe and Zn resulted in three and 11 folds' increase of these
      micronutrients in wheat respectively and significantly increased seed Ca, P, and
      S contents however acquisition and translocation of 20 mineral elements varied
      from tissue to tissue. The improvement of major crop species for health-related
      micronutrient is important for combating world- wide malnutrition problem. The
      higher concentration of one micronutrient element may not always ensure higher
      concentration of that element in seed but increase concentration of Fe and Zn may
      ensure higher concentrations of others important minerals in wheat seed. The
      results from our research unveiled key aspects on interrelation among some
      minerals and metals due to higher concentration of Fe, Zn, and Cd application in
      wheat.

PMID- 30221175
TI  - Effect of non-steroidal anti-inflammatory drugs on post-surgical complications
      against the backdrop of the opioid crisis.
AB  - The USA is currently going through an opioid crisis, associated with tremendous
      economic and societal impacts. In response to this crisis, healthcare
      professionals are looking for alternative pain management methods, and non
      steroidal anti-inflammatory drugs (NSAIDs) are a sensible choice because of their
      effectiveness after surgical procedures. However, before surgeons start
      prescribing NSAIDs in place of opioids, it is crucial to first understand their
      potential post-surgical complications. The goal of this review is to summarize
      the data obtained through both animal and human studies, which suggest how a
      dramatic increase in NSAID use may affect these post-surgical complications. We
      first provide a short review outlining the mechanisms of action of NSAIDs,
      followed by a summary of animal studies, which show a trend towards the negative
      effects of NSAIDs on wound healing and an association between NSAID use and wound
      infections. Lastly, we present evidence from human studies on the association of
      NSAIDs with the following complications: anastomotic leaks, necrotizing soft
      tissue infections, bleeding complications, orthopedic injuries, wound healing,
      and cancer care. The human studies are much more variable in their conclusions as
      to whether NSAIDs are beneficial or not, with the only strong evidence showing
      that NSAIDs inhibit bone healing. This may partially be explained by male and
      female differences in response to NSAIDs as many animal studies showing the
      inhibitory effects of NSAIDs were performed on females, while all the human
      studies were performed with both sexes. We conclude that strong caution should be
      used in the prescription of NSAIDs, especially in female patients, but larger
      scale studies are warranted before solid recommendations can be made.

PMID- 30221176
TI  - How Children and Adults Encode Causative Events Cross-Linguistically:
      Implications for Language Production and Attention.
AB  - This study investigates the implications of language-specific constraints on
      linguistic event encoding for the description and on-line inspection of causative
      events. English-speaking and Greek-speaking adults, 3-year-olds, and 4-year-olds
      viewed and described causative events, which are composed of Means and Result
      subevents, in an eyetracking study. The results demonstrate cross-linguistic
      differences in the informational content of causative event descriptions: Greek
      speakers across age groups were more likely than English speakers to mention only
      one causative subevent. Developmental changes in the tendency to encode
      information about causative events in language were also evident: in both
      language groups, adults were more likely than children to mention both Means and
      Result subevents. Finally, for both adult and child speakers of both languages,
      preparing different types of event descriptions changed the way that events were
      visually inspected, shifting attention toward to-be-encoded subevents. These
      findings offer some of the first evidence about the development of the language
      production system, the attentional mechanisms that it employs, and its workings
      in speakers of different languages.

PMID- 30221178
TI  - Measuring Sexual Minority Stressors in Lesbian Women's Daily Lives: Initial Scale
      Development.
AB  - Lesbian women face unique sexual minority stressors (SMS) due to their
      stigmatized and marginalized status in society. Existing studies of SMS are
      primarily cross-sectional and use global measures of SMS. The goal of the present
      study was to develop a brief daily measure of SMS for use in daily diary or
      ecological momentary assessment (EMA) studies. Existing retrospective measures of
      SMS were reviewed, resulting in an initial pool of 29 items. Thirty-eight lesbian
      women (Mage=24.3 years, range: 19-30 years) completed a daily web-based survey
      including the SMS items for 12 days. Two response scales were tested;
      participants were randomized to receive a 3-point (for brevity) or 7-point (for
      precision) scale for the first 6 days and the other response scale for the
      remaining 6 days to counterbalance order. Findings suggest the 7-point scale was
      optimal because it provided greater variability. To reduce scale length, item
      correlations were examined to identify clusters and one item was retained from
      each cluster, reducing the scale to 18 items. Then, using HLM, null models with
      each item as the outcome were conducted to examine level-1 and level-2 variances;
      8-, 10-, 12-, and 18-item scales were compared to identify the ideal number of
      items. The 8-item scale had the highest Cronbach's alpha (.85) and the smallest
      intraclass correlation (ICC; .13), suggesting these 8 items are optimal for
      capturing within-person variability in young lesbian women's daily SMS
      experiences. As researchers are increasingly interested in using EMA methods,
      this 8-item measure can assess SMS in lesbian women's everyday lives.

PMID- 30221177
TI  - The Role of Social Support and Gay Identity in the Stress Processes of a Sample
      of Caucasian Gay Men.
AB  - Though research has demonstrated that gay men suffer stress-related mental health
      disparities compared to heterosexuals, little is known about factors that protect
      gay individuals from poor mental health and that buffer them in the face of
      minority stress. Using a daily diary approach, the current study examined three
      factors that may protect individuals from poor mental health: social support from
      friends, social support from family, and gay identity. Caucasian gay men (N = 89)
      completed a study purported to examine the everyday life experiences of gay
      individuals. Participants completed baseline measures of social support from
      friends and family, gay identity (i.e., sense of belonging to the gay community),
      and depression. Participants then completed measures of minority stress and
      negative affect at the end of each day for 14 consecutive days. Though all three
      predictors were negatively related to depression at baseline, only friend support
      remained significant when all predictors were included simultaneously. For the
      daily data, HLM was used to examine the moderating role that each of the
      predictors served in the daily minority stress-mental health link. Only friend
      support moderated the link. Those with more friend support experienced little
      change in negative affect from average to above-average minority stress days.
      However, those with less support experienced increases in negative affect from
      average to above-average minority stress days. The research highlights the
      importance of friend support for coping, while also suggesting that predictors of
      minority stress may differ when stress is assessed retrospectively versus daily.

PMID- 30221180
TI  - Editorial Special Topic: Neuroscience, Learning, and Educational Practice
      Challenges, Promises, and Applications.
AB  - There is growing interest in the contributions of neuroscience to educational
      practice; however, to date, neuroscience seems to have had little impact on
      education. Nonetheless, neuroscience has potential value for education on several
      fronts, as illustrated by the articles in this Special Topic. These articles
      provide excellent examples for how neuroscientific approaches can complement
      behavioral work, and they demonstrate how understanding the neural level can help
      researchers develop richer models of learning and development. These articles
      further show that, ideally, research efforts in neuroscience and education should
      be reciprocal. Specifically, education should encourage psychology and
      neuroscience to develop learning theories that are relevant in the real world and
      further improve our understanding of how specific instructional practices affect
      learning and achievement; in turn, psychology and neuroscience can provide
      insights into underlying neural and cognitive mechanisms of learning, with the
      overall goal to maximize human potential and learning for all.

PMID- 30221179
TI  - Electron energy analysis by phase-space shaping with THz field cycles.
AB  - Time-resolved electron energy analysis and loss spectroscopy can reveal a wealth
      of information about material properties and dynamical light-matter interactions.
      Here, we report an all-optical concept for measuring energy spectra of
      femtosecond electron pulses with sub-eV resolution. Laser-generated terahertz
      radiation is used to measure arrival time differences within electron pulses with
      few-femtosecond precision. Controlled dispersion and subsequent compression of
      the electron pulses provide almost any desired compromise of energy resolution,
      signal strength, and time resolution. A proof-of-concept experiment on aluminum
      reveals an energy resolution of <3.5 eV (rms) at 70-keV after a drift distance of
      only 0.5 m. Simulations of a two-stage scheme reveal that pre-stretched pulses
      can be used to achieve <10 meV resolution, independent of the source's initial
      energy spread and limited only by the achievable THz field strength and measuring
      time.

PMID- 30221182
TI  - Ensuring Representativeness in Competencies for Research Coordinators.
AB  - Providing educational programs designed to promote clinical research
      coordinators' (CRCs') implementation of competency skills is essential to
      workforce development; however, little is known about how programs address CRCs'
      needs. The purpose of this study was to assess CRCs' experiences in a six-month
      course. Using focus group methods, six participants revealed how the training
      assisted them in daily work. The findings supported previous study results, and
      led to the identification of two competencies which are missing from the existing
      Joint Task Force for Clinical Trial Competency framework domains of
      "Communication and Teamwork" and "Leadership and Professionalism." The authors
      explain why these competencies are important for coordinators. The authors also
      discuss the instrumentality of qualitative research to ensure that competency
      domains reflect the needs of those for whom they are developed.

PMID- 30221181
TI  - The role of interest in memory for trivia questions: An investigation with a
      large-scale database.
AB  - The importance of interest for memory performance has been established in
      previous studies. One way to induce interest in experiments is to use trivia
      questions. However, previous studies have used only a limited number of trivia
      questions and these questions differ substantially across studies, making it
      difficult to ensure the comparability and generalizability of the findings. Most
      of these studies also have not differentiated between interest in the trivia
      question itself and interest in the corresponding answer. To address these
      issues, the current study established a normative database for 244 trivia
      questions with a large sample (N = 1498) and examined how pre-answer interest
      (i.e., interest in the question) and post-answer interest (i.e., interest in the
      answer) relate to learning performance. Participants were presented with trivia
      questions, asked to provide their best guess for the answer, rated their
      confidence in the guess, and indicated their interest in learning the true
      answer. Following the presentation of the answer, participants indicated their
      post-answer interest. One week later, participants were given a memory test on
      the questions. A multilevel structural equation model revealed that the positive
      relationship between pre-answer interest and memory was fully mediated by post
      answer interest (i.e., interest in the questions' answer). Confidence had both a
      direct and a mediated effect (over interest) on memory. These results provide a
      more fine-grained analysis of how interest can fuel learning.

PMID- 30221183
TI  - African American Screening and Enrollment in (Clot Lysis: Evaluating Accelerated
      Resolution of Intraventricular Hemorrhage III) CLEAR III.
AB  - Background: Under-enrolling minority patients in clinical trials reduces
      generalizability. CLEAR III, a randomized controlled trial, presented an
      opportunity to assess African American (AA) participation. Methods: AA enrollment
      was compared to U.S. population and NINDS trial data then stratified by region;
      census data for 42 recruitment cities were compared to screening and
      randomization percentages, using simple linear regression. Results: AAs were 25%
      of screens and 45.1% of enrollments (n=370), more than twice the 19.8%
      participation rate reported by the 2011 NINDS Advisory Panel on Health
      Disparities Research and triple the projected 13.9% 2014 U.S. population.
      Conversion rates were (AA vs. non-AA): overall (8.7% vs. 3.4%, p<0.001);
      Northeast (7.7% vs. 2.9%, p<0.001); South (8.2% vs. 4.0%, p<0.001); Midwest
      (10.3% vs. 3.6%, p<0.01); and West (8.9% vs. 3.8%, p=0.02). AA enrollments ranged
      from 0% to 100% (mean: 40.4%). AA screening ranged from 0% to 63.7% (mean:
      23.2%). AA city census ranged from 1.3% to 82.7% (mean: 28.0%); higher census was
      associated with higher screening (p<0.0001) and enrollment (p=0.004).
      Conclusions: AAs were willing to enroll in an acute stroke trial. AA city census
      rates should be considered when selecting enrollment centers and setting
      recruitment goals. Factors leading to successful AA recruitment should be further
      investigated, as population-based participation is a goal in all trials.

PMID- 30221184
TI  - Single-exposure optical focusing inside scattering media using binarized time
      reversed adapted perturbation.
AB  - Light scattering inhibits high-resolution optical imaging, manipulation and
      therapy deep inside biological tissue by preventing focusing. To form deep foci,
      wavefront shaping techniques that break the optical diffusion limit have been
      developed. For in vivo applications, such focusing must provide high gain, high
      speed, and a high focal peak-to-background ratio. However, none of the previous
      techniques meet these requirements simultaneously. Here, we overcome this
      challenge by rapidly measuring the perturbed optical field within a single camera
      exposure followed by adaptively time-reversing the phase-binarized perturbation.
      Consequently, a phase-conjugated wavefront is synthesized within a millisecond,
      two orders of magnitude shorter than the digitally achieved record. We
      demonstrated real-time focusing in dynamic scattering media, and extended laser
      speckle contrast imaging to new depths. The unprecedented combination of fast
      response, high gain, and high focusing contrast makes this work a major stride
      toward in vivo deep tissue optical imaging, manipulation, and therapy.

PMID- 30221185
TI  - Photodynamic therapy mediated immune therapy of brain tumors.
AB  - Photodynamic therapy of tumors requires the topical, systemic or oral
      administration of a photosensitizing compound, illumination of the tumor area by
      light of a specific wavelength and the presence of oxygen. Light activation of
      the photosensitizer transfers energy to molecular oxygen creating singlet oxygen,
      a highly reactive and toxic species that rapidly reacts with cellular components
      causing oxidative damage, ultimately leading to cell death. Tumor destruction
      caused by photodynamic therapy is not only a result of direct tumor cell toxicity
      via the generation of reactive oxygen species but there is also an immunological
      and vascular component involved. The immune response to photodynamic therapy has
      been demonstrated to significantly enhance its efficacy. Depending on a number of
      factors, including type of photosensitizer, light dose and dose rate,
      photodynamic therapy has been shown to induce cell death via apoptosis, necrosis,
      autophagy and in particular immunogenic cell death. It is the purpose of this
      review to focus mainly on the role photodynamic therapy could play in the
      generation of specific anti-tumor immunity and vaccines for the treatment of
      brain tumors.

PMID- 30221186
TI  - Sex Differences and the Effects of Estradiol on Striatal Function.
AB  - The striatal brain regions, including the caudate-putamen, nucleus accumbens
      core, and nucleus accumbens shell, mediate critical behavioral functions. These
      functions include but are not limited to motivated behavior, reward, learning,
      and sensorimotor function in both pathological and normal contexts. The phenotype
      and/or incidence of all of these behaviors either differ by sex or are sensitive
      to the presence of gonadal hormones such as 17beta-estradiol and testosterone.
      All three striatal brain regions express membrane-associated estrogen receptors.
      Here we present a brief review of the recent literature reporting on sex
      differences and effects of the estrogenic hormone 17beta-estradiol on behavioral
      and neural function across all three striatal regions, focusing upon the most
      prominent striatal neuron type, the medium spiny neuron. We emphasize recent
      findings in three broad domains: (1) select striatal-relevant behaviors and
      disorders, (2) striatal medium spiny neuron dendritic spine density, and (3),
      striatal medium spiny neuron electrophysiological properties including excitatory
      synaptic input and intrinsic cellular excitability. These recent advances in
      behavior, neuroanatomy, and electrophysiology collectively offer insight into the
      effects of sex and estrogen on striatal function, especially at the level of
      individual neurons.

PMID- 30221188
TI  - Devitalized Stem Cell Microsheets for Sustainable Release of Osteogenic and
      Vasculogenic Growth Factors and Regulation of Anti-Inflammatory Immune Response.
AB  - The objective of this work was to investigate the effect of devitalized human
      mesenchymal stem cells (hMSCs) and endothelial colony-forming cells (ECFCs)
      seeded on mineralized nanofiber microsheets on protein release, osteogenesis,
      vasculogenesis, and macrophage polarization. Calcium phosphate nanocrystals were
      grown on the surface of aligned, functionalized nanofiber microsheets. The
      microsheets were seeded with hMSCs, ECFCs, or a mixture of hMSCs+ECFCs, cultured
      for cell attachment, differentiated to the osteogenic or vasculogenic lineage,
      and devitalized by lyophilization. The release kinetic of total protein, bone
      morphogenetic protein-2 (BMP2), and vascular endothelial growth factor (VEGF)
      from the devitalized microsheets was measured. Next, hMSCs and/or ECFCs were
      seeded on the devitalized cell microsheets and cultured in the absence of osteo
      /vasculo-inductive factors to determine the effect of devitalized cell
      microsheets on hMSC/ECFC differentiation. Human macrophages were seeded on the
      microsheets to determine the effect of devitalized cells on macrophage
      polarization. Based on the results, devitalized undifferentiated hMSC and
      vasculogenic-differentiated ECFC microsheets had highest sustained release of
      BMP2 and VEGF, respectively. The devitalized hMSC microsheets did not affect M2
      macrophage polarization while vascular-differentiated, devitalized ECFC
      microsheets did not affect M1 polarization. Both groups stimulated higher M2
      macrophage polarization compared to M1.

PMID- 30221190
TI  - Advillin Is Expressed in All Adult Neural Crest-Derived Neurons.
AB  - Promoter-based genetic recombination (via, e.g., Cre-lox) is most useful when all
      cells of interest express a particular gene. The discovery that the actin-binding
      protein advillin is expressed in all somatic sensory neurons has been exploited
      repeatedly to drive DNA recombination therein, yet specificity of expression has
      not been well demonstrated. Here, we characterize advillin expression amongst
      sensory neurons and in several other neural and non-neural tissues. We first
      validate an advillin antibody against advillin knock-out tissue, advillin
      promoter-driven EGFP, and advillin mRNA expression. In the dorsal root ganglion
      (DRG), advillin is enriched in non-peptidergic nociceptors. We also show that
      advillin expression, and advillin promotor-driven EGFP and Cre-recombinase
      expression, occurs in multiple tissues including the dorsal habenula of the
      epithalamus, endocrine cells of the gut, Merkel cells in the skin, and most
      strikingly, throughout the autonomic nervous system (sympathetic,
      parasympathetic, and enteric neurons) in mice, rats, and non-human primates. In
      the mouse pelvic ganglion, advillin immunoreactivity is most intense in pairs of
      small neurons, and concentrated in spine-like structures on the axon initial
      segment contacted by sympathetic preganglionic axons. In autonomic targets (iris
      and blood vessels), advillin is distributed along cholinergic parasympathetic
      axons and in sympathetic varicosities. Developmentally, advillin expression is
      absent from sympathetics at postnatal day 4 but begins to emerge by day 7,
      accounting for previous reports (based on embryonic expression) of advillin's
      specificity to sensory neurons. These results indicate that caution is warranted
      in interpreting previous studies in which advillin-driven genomic editing is
      either constitutive or performed after postnatal day 4.

PMID- 30221187
TI  - Embedded Spheroids as Models of the Cancer Microenvironment.
AB  - To more accurately study the complex mechanisms behind cancer invasion,
      progression, and response to treatment, researchers require models that replicate
      both the multicellular nature and 3D stromal environment present in an in vivo
      tumor. Multicellular aggregates (i.e., spheroids) embedded in an extracellular
      matrix mimic are a prevalent model. Recently, quantitative metrics that fully
      utilize the capability of spheroids are described along with conventional
      experiments, such as invasion into a matrix, to provide additional details and
      insights into the underlying cancer biology. The review begins with a discussion
      of the salient features of the tumor microenvironment, introduces the early work
      on non-embedded spheroids as tumor models, and then concentrates on the successes
      achieved with the study of embedded spheroids. Examples of studies include cell
      movement, drug response, tumor cellular heterogeneity, stromal effects, and
      cancer progression. Additionally, new methodologies and those borrowed from other
      research fields (e.g., vascularization and tissue engineering) are highlighted
      that expand the capability of spheroids to aid future users in designing their
      cancer-related experiments. The convergence of spheroid research among the
      various fields catalyzes new applications and leads to a natural synergy.
      Finally, the review concludes with a reflection and future perspectives for
      cancer spheroid research.

PMID- 30221189
TI  - Automatic Cell Segmentation by Adaptive Thresholding (ACSAT) for Large-Scale
      Calcium Imaging Datasets.
AB  - Advances in calcium imaging have made it possible to record from an increasingly
      larger number of neurons simultaneously. Neuroscientists can now routinely image
      hundreds to thousands of individual neurons. An emerging technical challenge that
      parallels the advancement in imaging a large number of individual neurons is the
      processing of correspondingly large datasets. One important step is the
      identification of individual neurons. Traditional methods rely mainly on manual
      or semimanual inspection, which cannot be scaled for processing large datasets.
      To address this challenge, we focused on developing an automated segmentation
      method, which we refer to as automated cell segmentation by adaptive thresholding
      (ACSAT). ACSAT works with a time-collapsed image and includes an iterative
      procedure that automatically calculates global and local threshold values during
      successive iterations based on the distribution of image pixel intensities. Thus,
      the algorithm is capable of handling variations in morphological details and in
      fluorescence intensities in different calcium imaging datasets. In this paper, we
      demonstrate the utility of ACSAT by testing it on 500 simulated datasets, two
      wide-field hippocampus datasets, a wide-field striatum dataset, a wide-field cell
      culture dataset, and a two-photon hippocampus dataset. For the simulated datasets
      with truth, ACSAT achieved >80% recall and precision when the signal-to-noise
      ratio was no less than ~24 dB.

PMID- 30221191
TI  - The Impact of gamma-Irradiation and EtO Degassing on Tissue Remodeling of
      Collagen-based Hybrid Tubular Templates.
AB  - Clinical implementation of novel products for tissue engineering and regenerative
      medicine requires a validated sterilization method. In this study, we
      investigated the effect of gamma-irradiation and EtO degassing on material
      characteristics in vitro and the effect on template remodeling of hybrid tubular
      constructs in a large animal model. Hybrid tubular templates were prepared from
      type I collagen and Vicryl polymers and sterilized by 25 kGray of gamma
      irradiation or EtO degassing. The in vitro characteristics were extensively
      studied, including tensile strength analysis and degradation studies. For in vivo
      evaluation, constructs were subcutaneously implanted in goats for 1 month to form
      vascularized neo-tissue. Macroscopic and microscopic appearances of the gamma-
      and EtO-sterilized constructs slightly differed due to additional processing
      required for the COL-Vicryl-EtO constructs. Regardless of the sterilization
      method, incubation in urine resulted in fast degradation of the Vicryl polymer
      and decreased strength (<7 days). Incubation in SBF was less invasive, and
      strength was maintained for at least 14 days. The difference between the two
      sterilization methods was otherwise limited. In contrast, subcutaneous
      implantation showed that the effect of sterilization was considerable. A well
      vascularized tube was formed in both cases, but the gamma-irradiated construct
      showed an organized architecture of vasculature and was mechanically more
      comparable to the native ureter. Moreover, the gamma-irradiated construct showed
      advanced tissue remodeling as shown by enhanced ECM production. This study shows
      that the effect of sterilization on tissue remodeling cannot be predicted by in
      vitro analyses alone. Thus, validated sterilization methods should be
      incorporated early in the development of tissue engineered products, and this
      requires both in vitro and in vivo analyses.

PMID- 30221192
TI  - Modulating Bone Regeneration in Rabbit Condyle Defects with Three Surface
      Structured Tricalcium Phosphate Ceramics.
AB  - Tricalcium phosphate (TCP) ceramics are used as bone void fillers because of
      their bioactivity and resorbability, while their performance in bone regeneration
      and material resorption vary with their physical properties (e.g., the dimension
      of the crystal grain). Herein, three TCP ceramic bone substitutes (TCP-S, TCP-M,
      and TCP-L) with gradient crystal grain size (0.77 +/- 0.21 MUm for TCP-S, 1.21 +/
      0.35 MUm for TCP-M and 4.87 +/- 1.90 MUm for TCP-L), were evaluated in a well
      established rabbit lateral condylar defect model (validated with sham) with
      respect to bone formation and material resorption up to 26 weeks. Surface
      structure-dependent bone regeneration was clearly shown after 4 weeks
      implantation with TCP-S having most mineralized bone (20.2 +/- 3.4%), followed by
      TCP-M (14.0 +/- 3.5%), sham (8.1 +/- 4.2%), and TCP-L (6.6 +/- 2.6%). Afterward,
      the amount of mineralized bone was similar in all the three groups, but bone
      marrow and material resorption varied. After 26 weeks, TCP-S induced most bone
      tissue formation (mineralized bone + bone marrow) (61.6 +/- 7.8%) and underwent
      most material resorption (80.1 +/- 9.0%), followed by TCP-M (42.9 +/- 5.2% and
      61.4 +/- 8.0% respectively), TCP-L (28.3 +/- 5.5% and 45.6 +/- 9.7%
      respectively), and sham (25.7 +/- 4.2%). Given the fact that the three ceramics
      are chemically identical, the results indicate that the surface structure
      (especially, the crystal grain size) of TCP ceramics can greatly tune their bone
      regeneration potential and the material resorption in rabbit condyle defect
      model, with the submicron surface structured TCP ceramic performing the best.

PMID- 30221193
TI  - Rapid Progression of Heart Failure in a Patient with Idiopathic Inflammatory
      Myopathy.
AB  - Idiopathic inflammatory myopathy (IIM) is a rare autoimmune myopathy that
      includes polymyositis, dermatomyositis, inclusion body myositis and autoimmune
      necrotizing myositis. Cardiac involvement was considered a rare occurrence in IIM
      however, recent reports suggests that cardiac involvement is a common feature and
      portends poor prognosis as it is usually encountered in advanced disease. IIM
      leads to myocarditis with subsequent development of myocardial fibrosis, cardiac
      conduction system disease and cardiomyopathy resulting in both systolic and
      diastolic heart failure. Conduction abnormalities such as first, second and third
      degree atrioventricular blocks, right and left bundle branch blocks associated
      with IIM have been reported. We present a case of a 44-year-old woman with biopsy
      proven-IIM whose left ventricular ejection fraction (LVEF) and electrocardiogram
      (ECG) were recorded as normal two years prior. On presentation to our hospital
      ECG revealed atrial tachycardia and 2D echocardiogram revealed heart failure with
      reduced ejection fraction (20-30%). Patient quickly progressed to complete heart
      block. A cardiac resynchronization therapy-defibrillator (CRT-D) insertion was
      planned but patient succumbed to sepsis.

PMID- 30221194
TI  - The adjuvant GLA-AF enhances human intradermal vaccine responses.
AB  - Adjuvants are key to shaping the immune response to vaccination, but to date, no
      adjuvant suitable for human use has been developed for intradermal vaccines.
      These vaccines could be self-administered and sent through the mail as they do
      not require long needles or technical expertise in immunization. In the event of
      a pandemic outbreak, this approach could alleviate the congregation of patients
      in health centers and thus reduce the potential of these centers to enhance the
      spread of lethal infection. A reliable and potent vaccine system for self
      administration would provide an effective countermeasure for delivery through
      existing product distribution infrastructure. We report results from preclinical
      and clinical trials that demonstrate the feasibility of an adjuvanted,
      intradermal vaccine that induced single shot protection in ferrets and
      seroprotection in humans against one of the more lethal strains of pandemic flu,
      Indonesia H5N1. In the human trial, the vaccine was safe and clinical responses
      were above approvable endpoints for a protective flu vaccine. Inclusion of a
      modern TLR4 (Toll-like receptor 4) agonist-based adjuvant was critical to the
      development of the response in the intradermal groups. In humans, this is the
      first report of a safe and effective intradermal adjuvant, GLA-AF (aqueous
      formulation of glucopyranosyl lipid adjuvant), and provides a future path for
      developing a vaccine-device combination for distribution by mail and self
      administration in case of a pandemic.

PMID- 30221196
TI  - Who Is This "We" You Speak of? Grounding Activist Identity in Social Psychology.
AB  - What is an activist identity? Prior answers have focused almost exclusively on
      collective identity, without a) considering the possibility of role-based
      identities or b) grounding collective identities in broader social-psychological
      theories. The present study investigates activist identity through the lens of
      role-based and category-based identities, and reports two major findings. First,
      there is a distinct role-based activist identity, one that involves internalizing
      role responsibilities and the expectations of friends and family. Second,
      collective identity represents a relationship between a social identity and an
      injustice frame; it either involves incorporating an injustice frame into a pre
      existing social identity, or using the injustice frame to create a new in-group.
      The present findings help to illuminate the processes underlying collective
      identity, indicate that a great deal of role-based activist identity is mistaken
      for collective identity, and suggest new directions for the study of micro
      mobilization and organizational forms and tactics in social movements.

PMID- 30221195
TI  - Weight stigma facilitates unhealthy eating and weight gain via fear of fat.
AB  - Objective: Across two studies, we examine if the relationships between perceived
      weight stigma, maladaptive eating behaviors (Study 1 & 2) and weight gain (Study
      2) are mediated by fear of fat (FOF). Method: In Study 1, 189 participants
      completed measures of eating behavior (e.g., emotional and restrained eating),
      FOF, perceived weight stigma and height and weight. In Study 2, a longitudinal
      design, participants reported their perceived weight stigma, FOF and had their
      height and weight measured; they then returned 10 weeks later to complete
      measures of eating behaviors (e.g., flexible restraint, ridged restraint, and
      emotional eating) and height and weight. We examined the predictive value of
      weight stigma at session 1 on eating behavior and weight gain at session 2.
      Further, we examined FOF as a mediator of these relationships. Results: In Study
      1, we found that FOF significantly mediated the positive relationship between
      perceived weight stigma and restrained eating behavior (b=.13, CI: .09 to .19).
      In Study 2, we found that perceived weight stigma predicted weight gain over the
      10-week period and that this relationship was mediated by both FOF (b=.31, CI:
      .03 to .78) and rigid restraint of eating (b=.07, CI: .002 to .28). Flexible
      restraint and emotional eating behavior were not mediators of the relationship
      between perceived weight stigma and weight gain. Conclusion: Fear of fat may be
      one process through which perceptions of weight stigma lead to maladaptive eating
      behavior and weight gain. Understanding this important process may lead to more
      effective healthy weight interventions.

PMID- 30221198
TI  - Motor Control-based Group Exercise: Can It be Delivered as Effectively by Lay
      Leaders?
AB  - Purpose: On the Move (OTM), a motor control-based group exercise program for
      community-dwelling older adults, has produced greater gains in mobility than a
      standard group exercise program when delivered by research leaders. The purposes
      of this study were:1) to examine the effectiveness of OTM versus a standard
      program when delivered by lay leaders and 2) to compare the outcomes of OTM when
      delivered by research versus lay leaders. Methods: Community-dwelling, medically
      stable older adults who could walk household distances participated. OTM
      consisted of warm-up, timing and coordination, strengthening, and stretching
      exercises. The seated standard program consisted of warm-up, aerobic,
      strengthening and stretching exercises. The primary outcome(s) of function and
      disability was the Late Life Function and Disability Instrument (LLFDI), and for
      walking ability were the Six Minute Walk Test and gait speed. Results: 126
      participants (mean age = 80.7+/-7.8 years, gait speed = 0.91 m/s) were randomized
      to OTM (n=49) or standard (n=77) programs. When taught by lay leaders, there were
      no significant between-intervention group differences in any of the outcomes
      (p>0.10). Comparing OTM outcomes between leaders, there was a statistical but not
      clinically meaningful difference in LLFDI disability (1.87+/-0.89, p=0.04) when
      taught by research versus lay leader, and moderate differences (p=0.06) in LLFDI
      overall function (1.89+/-1.02) and gait speed (0.05+/-0.03). Qualitative
      interview responses suggest that instructor-related concerns may have impacted
      program outcomes. Conclusion: When delivered by lay leaders OTM was not more
      effective than a standard program for improving function, disability, and
      mobility in older adults. Health promotion programs designed to improve mobility
      in community-dwelling older adults and based on a motor control theoretical
      background, may be best taught by rehabilitation professionals.

PMID- 30221199
TI  - Bilateral Ureteral Obstruction Caused by Stone Formation After Laparoscopic
      Appendectomy in Children.
AB  - In children, urologic complications are rare after laparoscopic appendectomy
      (LA). In this article, we report the case of a 9-year-old boy with bilateral
      hydronephrosis caused by ureteral calculi 10 days after he had undergone LA. The
      patient's urinary output normalized and renal function recovered after stone
      extraction and bilateral ureteral stent insertion.

PMID- 30221200
TI  - Where Spanish and English Come Together: A Two Dimensional Bilingual Approach to
      Clinical Decision Making.
AB  - An increasing number of United States school children are from culturally and
      linguistically diverse (CLD) backgrounds and speak multiple languages. Speech
      language pathologists (SLPs) are often challenged with differentiating the
      performance of bilingual children with language impairment from those who may
      display a language difference. While there is consensus that we should consider
      both languages of a bilingual child in formal and informal assessments, there is
      no agreed way to interpret results of testing in both languages. The aim of this
      article is to propose a framework for conducting and interpreting the results
      from comprehensive and unbiased evaluations that incorporate language samples,
      parent and teacher reports, and standardized testing. We will illustrate the use
      of this bilingual coordinate approach via a pair of case studies.

PMID- 30221197
TI  - Emerging Evidence for Cannabis' Role in Opioid Use Disorder.
AB  - Introduction: The opioid epidemic has become an immense problem in North America,
      and despite decades of research on the most effective means to treat opioid use
      disorder (OUD), overdose deaths are at an all-time high, and relapse remains
      pervasive. Discussion: Although there are a number of FDA-approved opioid
      replacement therapies and maintenance medications to help ease the severity of
      opioid withdrawal symptoms and aid in relapse prevention, these medications are
      not risk free nor are they successful for all patients. Furthermore, there are
      legal and logistical bottlenecks to obtaining traditional opioid replacement
      therapies such as methadone or buprenorphine, and the demand for these services
      far outweighs the supply and access. To fill the gap between efficacious OUD
      treatments and the widespread prevalence of misuse, relapse, and overdose, the
      development of novel, alternative, or adjunct OUD treatment therapies is highly
      warranted. In this article, we review emerging evidence that suggests that
      cannabis may play a role in ameliorating the impact of OUD. Herein, we highlight
      knowledge gaps and discuss cannabis' potential to prevent opioid misuse (as an
      analgesic alternative), alleviate opioid withdrawal symptoms, and decrease the
      likelihood of relapse. Conclusion: The compelling nature of these data and the
      relative safety profile of cannabis warrant further exploration of cannabis as an
      adjunct or alternative treatment for OUD.

PMID- 30221201
TI  - Remote ischemic conditioning: a treatment for vascular cognitive impairment.
AB  - There is a strong link between hypoperfusion and white matter (WM) damage in
      patients with leukoaraiosis and vascular cognitive impairment (VCI). Other than
      management of vascular risk factors, there is no treatment for WM damage and VCI
      that delays progression of the disease process to dementia. Observational studies
      suggest that exercise may prevent or slow down the progression of Alzheimer's
      disease (AD) and VCI. However, getting patients to exercise is challenging
      especially with advancing age and disability. Remote ischemic conditioning, an
      "exercise equivalent", allows exercise to be given with a "device" in the home
      for long periods of time. Since RIC increases CBF in pre-clinical studies and in
      humans, RIC may be an ideal therapy to treat VCI and WM disease and perhaps even
      sporadic AD. By using MRI imaging of WM progression, a sample size in the range
      of about 100 subjects per group could determine if RIC has activity in WM disease
      and VCI.

PMID- 30221202
TI  - Diversity in pitch perception revealed by task dependence.
AB  - Pitch conveys critical information in speech, music, and other natural sounds,
      and is conventionally defined as the perceptual correlate of a sound's
      fundamental frequency (F0). Although pitch is widely assumed to be subserved by a
      single F0 estimation process, real-world pitch tasks vary enormously, raising the
      possibility of underlying mechanistic diversity. To probe pitch mechanisms we
      conducted a battery of pitch-related music and speech tasks using conventional
      harmonic sounds and inharmonic sounds whose frequencies lack a common F0. Some
      pitch-related abilities - those relying on musical interval or voice recognition 
      were strongly impaired by inharmonicity, suggesting a reliance on F0. However,
      other tasks, including those dependent on pitch contours in speech and music,
      were unaffected by inharmonicity, suggesting a mechanism that tracks the
      frequency spectrum rather than the F0. The results suggest that pitch perception
      is mediated by several different mechanisms, only some of which conform to
      traditional notions of pitch.

PMID- 30221203
TI  - Event segmentation protects emotional memories from competing experiences encoded
      close in time.
AB  - Fear memories are characterized by their permanence and a fierce resistance to
      unlearning by new experiences. We considered whether this durability involves a
      process of memory segmentation that separates competing experiences. To address
      this question, we used an emotional learning task designed to measure recognition
      memory for category exemplars encoded during competing experiences of fear
      conditioning and extinction. Here we show that people recognized more fear
      conditioned exemplars encoded during conditioning than conceptually related
      exemplars encoded immediately after a perceptual event boundary separating
      conditioning from extinction. Selective episodic memory depended on a period of
      consolidation, an explicit break between competing experiences, and was unrelated
      to within-session arousal or the explicit realization of a transition from
      conditioning to extinction. Collectively, these findings suggest that event
      boundaries guide selective consolidation to prioritize emotional information in
      memory-at the expense of related but conflicting information experienced shortly
      thereafter. We put forward a model whereby event boundaries bifurcate related
      memory traces for incompatible experiences. This stands in contrast to a
      mechanism that integrates related experiences for adaptive generalization123, and
      reveals a potentially distinct organization by which competing memories are
      adaptively segmented to select and protect nascent fear memories from immediate
      sources of interference.

PMID- 30221205
TI  - Low-Intensity Vibration Improves Muscle Healing in a Mouse Model of Laceration
      Injury.
AB  - Recovery from traumatic muscle injuries is typically prolonged and incomplete,
      leading to impaired muscle and joint function. We sought to determine whether
      mechanical stimulation via whole-body low-intensity vibration (LIV) could (1)
      improve muscle regeneration and (2) reduce muscle fibrosis following traumatic
      injury. C57BL/6J mice were subjected to a laceration of the gastrocnemius muscle
      and were treated with LIV (0.2 g at 90 Hz or 0.4 g at 45 Hz for 30 min/day) or
      non-LIV sham treatment (controls) for seven or 14 days. Muscle regeneration and
      fibrosis were assessed in hematoxylin and eosin or Masson's trichrome stained
      muscle cryosections, respectively. Compared to non-LIV control mice, the myofiber
      cross-sectional area was larger in mice treated with each LIV protocol after 14
      days of treatment. Minimum fiber diameter was also larger in mice treated with
      LIV of 90 Hz/0.2 g after 14 days of treatment. There was also a trend toward a
      reduction in collagen deposition after 14 days of treatment with 45 Hz/0.4 g (p =
      0.059). These findings suggest that LIV may improve muscle healing by enhancing
      myofiber growth and reducing fibrosis. The LIV-induced improvements in muscle
      healing suggest that LIV may represent a novel therapeutic approach for improving
      the healing of traumatic muscle injuries.

PMID- 30221207
TI  - Pancreatic surgery.

PMID- 30221206
TI  - Role of secretory clusterin in hepatocarcinogenesis.
AB  - Secretory clusterin (sCLU) is a small stress-induced cytoprotective chaperone
      protein. Its biological functions are similar to those of a heat-shock protein.
      The sCLU plays a crucial role in cell proliferation, multiple drug resistance,
      metastasis, and tumor progression. Abnormal sCLU expression in tumor tissues or
      sera of patients with primary hepatic cancer has been considered a useful
      biomarker for diagnosis and surveillance. However, the exact relationship between
      sCLU overexpression and malignant transformation of hepatocytes is still unknown.
      The present review examines some novel advances of the knowledge about the
      oncogenic role of sCLU in hepatocarcinogenesis.

PMID- 30221204
TI  - Retrosplenial cortex and its role in spatial cognition.
AB  - Retrosplenial cortex is a region within the posterior neocortical system, heavily
      interconnected with an array of brain networks, both cortical and subcortical,
      that is, engaged by a myriad of cognitive tasks. Although there is no consensus
      as to its precise function, evidence from both human and animal studies clearly
      points to a role in spatial cognition. However, the spatial processing
      impairments that follow retrosplenial cortex damage are not straightforward to
      characterise, leading to difficulties in defining the exact nature of its role.
      In this article, we review this literature and classify the types of ideas that
      have been put forward into three broad, somewhat overlapping classes: (1)
      learning of landmark location, stability and permanence; (2) integration between
      spatial reference frames; and (3) consolidation and retrieval of spatial
      knowledge (schemas). We evaluate these models and suggest ways to test them,
      before briefly discussing whether the spatial function may be a subset of a more
      general function in episodic memory.

PMID- 30221208
TI  - Reviving a 60 million year old LINE-1 element.
AB  - Mobile elements have significantly impacted genome structure of most organisms.
      The continued activity of the mobile element, LINE-1 (L1), through time has
      contributed to the accumulation of over half a million L1 copies in the human
      genome. Most copies in the human genome belong to evolutionary older extinct L1s.
      Here we apply our previous published approach to "revive" the extinct L1 PA13A;
      an L1 family that was active about 60 million year ago (mya). The reconstructed
      L1PA13A is retrocompentent in culture, but shows a significantly lower level of
      activity in HeLa cells when compared to the modern L1 element (L1PA1) and a 40
      million year old L1PA8. L1 elements code for two proteins (ORF1p and ORF2p) that
      are necessary for retrotransposition. Using PA13A-PA1 and PA13A-PA8 L1 chimeric
      elements, we determined that both the ORF1p and ORF2p contribute to the observed
      decrease in retrotransposition efficiency of L1PA13A. The lower
      retrotransposition rate of L1PA13A is consistent in both human and rodent cell
      lines. However, in rodent cells, the chimeric element L1PA:1-13 containing the
      modern L1PA1 ORF1p shows a recovery in the retrotransposition rate, suggestive
      that the L1PA13A ORF2p efficiently drives retrotransposition in these cells. The
      functionality of the L1PA13A ORF2p was further confirmed by demonstrating its
      ability to drive Alu retrotransposition in rodent cells. The variation in L1PA13A
      retrotransposition rates observed between rodent and human cells are suggestive
      that cellular environment significantly affects retrotransposition efficiency,
      which may be mediated through an interaction with ORF1p. Based on these
      observations, we speculate that the observed differences between cell lines may
      reflect an evolutionary adaptation of the L1 element to its host cell.

PMID- 30221209
TI  - Genome Stability during Cell Proliferation: A Systems Analysis of the Molecular
      Mechanisms Controlling Progression through the Eukaryotic Cell Cycle.
AB  - Well-nourished cells in a favorable environment (well supplied with growth
      factors, cytokines, and/or hormones and free from stresses, ionizing radiation,
      etc.) will grow, replicate their genome, and divide into two daughter cells,
      fully prepared to repeat the process. This cycle of DNA replication and division
      underlies all aspects of biological growth, reproduction, repair and development.
      As such, it is essential that the cell's genome be guarded against damage during
      the replication/division process, lest the error(s) be irrevocably passed down to
      all future generations of progeny. Hence, cell cycle progression is closely
      guarded against major sources of errors, in particular DNA damage and
      misalignment of replicated chromosomes on the mitotic spindle. In this review
      article we examine closely the molecular mechanisms that maintain genomic
      integrity during the cell division cycle, and we find an unexpected and
      intriguing arrangement of concatenated and nested bistable toggle switches. The
      topology of the network seems to play crucial roles in maintaining the stability
      of the genome during cell proliferation.

PMID- 30221210
TI  - An Open-Source, Programmable Pneumatic Setup for Operation and Automated Control
      of Single- and Multi-Layer Microfluidic Devices.
AB  - Microfluidic technologies have been used across diverse disciplines (e.g. high
      throughput biological measurement, fluid physics, laboratory fluid manipulation)
      but widespread adoption has been limited in part due to the lack of openly
      disseminated resources that enable non-specialist labs to make and operate their
      own devices. Here, we report the open-source build of a pneumatic setup capable
      of operating both single and multilayer (Quake-style) microfluidic devices with
      programmable scripting automation. This setup can operate both simple and complex
      devices with 48 device valve control inputs and 18 sample inputs, with modular
      design for easy expansion, at a fraction of the cost of similar commercial
      solutions. We present a detailed step-by-step guide to building the pneumatic
      instrumentation, as well as instructions for custom device operation using our
      software, Geppetto, through an easy-to-use GUI for live on-chip valve actuation
      and a scripting system for experiment automation. We show robust valve actuation
      with near real-time software feedback and demonstrate use of the setup for high
      throughput biochemical measurements on-chip. This open-source setup will enable
      specialists and novices alike to run microfluidic devices easily in their own
      laboratories.

PMID- 30221211
TI  - Navigating through the minefield of read-across tools: A review of in silico
      tools for grouping.
AB  - Read-across is a popular data gap filling technique used within analogue and
      category approaches for regulatory purposes. In recent years there have been many
      efforts focused on the challenges involved in read-across development, its
      scientific justification and documentation. Tools have also been developed to
      facilitate read-across development and application. Here, we describe a number of
      publicly available read-across tools in the context of the category/analogue
      workflow and review their respective capabilities, strengths and weaknesses. No
      single tool addresses all aspects of the workflow. We highlight how the different
      tools complement each other and some of the opportunities for their further
      development to address the continued evolution of read-across.

PMID- 30221213
TI  - High-dose intraocular delivery of epinephrine by an auto-injector causing retinal
      trauma without arterial occlusion.

PMID- 30221212
TI  - The sbv IMPROVER Systems Toxicology Computational Challenge: Identification of
      Human and Species-Independent Blood Response Markers as Predictors of Smoking
      Exposure and Cessation Status.
AB  - Cigarette smoking entails chronic exposure to a mixture of harmful chemicals that
      trigger molecular changes over time, and is known to increase the risk of
      developing diseases. Risk assessment in the context of 21st century toxicology
      relies on the elucidation of mechanisms of toxicity and the identification of
      exposure response markers, usually from high-throughput data, using advanced
      computational methodologies. The sbv IMPROVER Systems Toxicology computational
      challenge (Fall 2015-Spring 2016) aimed to evaluate whether robust and sparse
      (<=40 genes) human (sub-challenge 1, SC1) and species-independent (sub-challenge
      2, SC2) exposure response markers (so called gene signatures) could be extracted
      from human and mouse blood transcriptomics data of current (S), former (FS) and
      never (NS) smoke-exposed subjects as predictors of smoking and cessation status.
      Best-performing computational methods were identified by scoring anonymized
      participants' predictions. Worldwide participation resulted in 12 (SC1) and six
      (SC2) final submissions qualified for scoring. The results showed that blood gene
      expression data were informative to predict smoking exposure (i.e. discriminating
      smoker versus never or former smokers) status in human and across species with a
      high level of accuracy. By contrast, the prediction of cessation status (i.e.
      distinguishing FS from NS) remained challenging, as reflected by lower
      classification performances. Participants successfully developed inductive
      predictive models and extracted human and species-independent gene signatures,
      including genes with high consensus across teams. Post-challenge analyses
      highlighted "feature selection" as a key step in the process of building a
      classifier and confirmed the importance of testing a gene signature in
      independent cohorts to ensure the generalized applicability of a predictive model
      at a population-based level. In conclusion, the Systems Toxicology challenge
      demonstrated the feasibility of extracting a consistent blood-based smoke
      exposure response gene signature and further stressed the importance of
      independent and unbiased data and method evaluations to provide confidence in
      systems toxicology-based scientific conclusions.

PMID- 30221215
TI  - Ellipsoid Zone Mapping Parameters In Retinal Venous Occlusive Disease With
      Associated Macular Edema.
AB  - Purpose: To evaluate the association of baseline ellipsoid zone (EZ) parameters
      on optical coherence tomography (OCT) as calculated by a semi-automated computer
      algorithm with baseline visual acuity in eyes with retinal vein occlusion (RVO).
      Design: Retrospective consecutive case series. Subjects: Patients affected by RVO
      presenting from January 2011 to December 2014. Methods: Baseline demographics,
      clinical characteristics, and SD-OCT data at presentation were collected. Macular
      cube scans were exported into a retinal layer analysis software platform and
      outer retinal parameters were evaluated. Outer retinal/EZ parameters included EZ
      retinal pigment epithelium (RPE) volume, central foveal EZ-RPE area, EZ-RPE
      central subfield thickness (CST), and EZ-RPE central foveal thickness (CFT). In
      addition, en face EZ mapping features were extracted including percent area with
      EZ attenuation (i.e., EZ-RPE thickness < 20 MUm) and percent area with total EZ
      loss (i.e., EZ-RPE thickness = 0 MUm). Main Outcome Measure: Correlation of EZ
      parameters and baseline visual acuity (VA). Secondary outcome measures:
      Correlation of EZ parameters with other clinical characteristics and OCT measures
      of cube volume, cube average thickness, central subfield thickness. Results: One
      hundred and twelve eyes were included in this analysis. Mean baseline VA was
      56.53 +/-17.68 ETDRS letters and was inversely associated with total EZ loss and
      EZ-RPE attenuation (r= - 0.33 and -0.38 respectively, p<0.001). VA was directly
      associated with all other EZ parameters (r=0.37 to 0.45, p<0.001). The presence
      of subretinal fluid was strongly linked to central parameters of central foveal
      EZ-RPE, EZ-RPE-CST, and EZ-RPE-CFT (Kruskal-Wallis test). Conventional OCT
      parameters (central subfield retinal thickness, cube volume and cube average
      thickness) did not have significant correlations with EZ measures (-0.3<R<0.3
      and/or P>0.05). Conclusion: Baseline EZ integrity is closely linked to presenting
      visual acuity in eyes with RVO and macular edema. EZ mapping provides an
      additional metric for evaluating RVO impact on retinal anatomy and potential
      function.

PMID- 30221216
TI  - Relationship Status and Sexual Behaviors in Post-Pelvic Inflammatory Disease
      (PID) Affected Urban Young Women: A Sub-Study of a Randomized Controlled Trial.
AB  - Adolescent and young adult women disproportionately experience Pelvic
      Inflammatory Disease (PID) as a complication of Sexually Transmitted Infections
      (STIs). This study seeks to understand the relationship context, changes in
      sexual behavior, and impact of partner sexual behavior on recurrent STI diagnoses
      at 3-months post-diagnosis. Adolescents and young adult women 13-25 were
      recruited from an outpatient disposition from an outpatient clinic, and pediatric
      and adult emergency rooms. Participants received treatment at baseline and follow
      up at 2-weeks, 1-month and 3-month post-diagnosis, including interviews about
      personal and partner sexual behaviors and STI screening (n = 94). At the 2-week
      interview, 53% of participants (50/94) believed they could acquire an STI from
      their current partner if they did not use a condom. However, at 3-month follow-up
      only 35% reported condom usage at last sex. At 3-month follow-up, 55% (50/91) of
      participants were still in a sexual relationship with the previously reported
      partner and 38% of participants who reported they could get an STI from their
      partner were diagnosed with an STI; compared with 25% of participants who
      predicted that they could not get an STI (OR 1.85; 95% CI: 0.67-5.30). There was
      no association between maintaining the same partner and having an STI at 3-months
      (OR 0.5; 95% CI: 0.27-1.96). Most young women diagnosed with PID report exclusive
      relationships, but are simultaneously aware of their risk for recurrent STIs.
      Given the short-term stability of many relationships, couples interventions are
      an unexplored opportunity for prevention of recurrent STIs after PID.

PMID- 30221214
TI  - Suspended Scattering Particles in Motion: A Novel Feature of OCT Angiography in
      Exudative Maculopathies.
AB  - Objective: To characterize features of extra-vascular optical coherence
      tomography angiography (OCTA) signals corresponding to hyperreflective
      intraretinal fluid across various exudative maculopathies. Design: Multicenter,
      retrospective, observational study. Participants: Eyes with various forms of
      exudative maculopathy including diabetic retinopathy (DR), retinal vein occlusion
      (RVO), and neovascular-age related macular degeneration (nvAMD). Methods:
      Patients with extra-vascular OCTA signal identified on en face OCTA images were
      included in this study. This signal was readily distinguishable from projection
      artifacts. The regions with the extra-vascular motion signal on OCTA were named
      "Suspended Scattering Particles in Motion (SSPiM)." Depth-encoded, color, en face
      OCTA images (3mm * 3mm) centered on the fovea and their corresponding structural
      OCT scans were used to quantify features of SSPiM and its corresponding
      hyperreflective fluid. Longitudinal data were collected when available. Main
      outcome measures: Anatomic location, the association with hyperreflective
      material, changes in location and appearance of SSPiM over time, and replication
      of SSPiM OCTA signal in an in vitro phantom. Results: Seventy-six eyes in 62
      patients with various forms of exudative maculopathy were evaluated; 60 eyes with
      DR, 9 eyes with RVO, and 5 eyes nvAMD, 1 eye with macroaneurysm, and 1 eye with
      radiation retinopathy. Intraretinal accumulations of fluid with increased OCT
      signal intensity corresponded to regions of SSPiM in several exudative
      maculopathies. An in vitro phantom model demonstrates that particulate matter in
      suspension can generate similar OCTA signal. SSPiM showed an anatomic preference
      for vascular-avascular junctions. The hyperreflective fluid corresponding to
      SSPiM appeared more frequently in Henle's fiber layer (HFL) than the inner
      nuclear layer (INL) and was highly associated with hyperreflective material (HRM)
      found bordering the fluid. In five of eight longitudinal cases, the resolution of
      SSPiM resulted in the formation of confluent HRM. Clinically, this appeared as
      hard exudate on funduscopic images. Conclusions: Clinical data suggest that SSPiM
      is a novel imaging feature of retinal vascular diseases that was not appreciated
      prior to the use of OCTA. We characterized several novel features of SSPiM and
      demonstrated that at least in some cases it resolves with residual hard exudate.

PMID- 30221217
TI  - Exploring Selectivity of Multikinase Inhibitors across the Human Kinome.
AB  - Selectivity of kinase inhibitors, or the lack thereof, continues to be an
      intensely debated topic in drug discovery research. Especially, type I
      inhibitors, which represent most of the currently available kinase inhibitors,
      are often thought to lack selectivity because they target the largely conserved
      adenosine triphosphate-binding site in kinases. Herein, we present a large-scale
      analysis of potential selectivity among multikinase inhibitors, covering 141
      human kinases and more than 10 000 qualifying compounds. By design, the analysis
      was focused on type I inhibitors and carried out at the level of systematically
      generated kinase pairs sharing inhibitors. Kinase pair category- and compound
      based selectivity profiles identified in part highly selective inhibitors for
      many kinases. Sets of inhibitors associated with kinase pairs frequently
      contained nonselective as well as increasingly selective compounds. Selectivity
      of inhibitors did not result from gatekeeper residues settings or phylogenetic
      distance of kinases. Rather, it was most likely attributable to subtle
      differences between binding regions in kinases. Taken together, the results of
      our study reveal that many multikinase inhibitors are more selective than one
      might assume.

PMID- 30221218
TI  - Combined Adsorption and Covalent Linking of Paclitaxel on Functionalized Nano
      Graphene Oxide for Inhibiting Cancer Cells.
AB  - Developing targeted delivery nanosystems for delivering chemotherapeutic
      anticancer drugs specifically to cancerous tissues with improvement in the
      specificity of drugs for different cancer cells can result in high therapeutic
      efficacy and low toxicity in healthy tissues. Herein, we proposed the synthesis
      of a multifunctional nanodelivery system, folic acid (FA) decorating nanographene
      oxide (nGO) functionalized with poly(ethylene glycol) (PEG), called pGO-FA, with
      good biocompatibility and good delivering performance of a hydrophobic water
      insoluble anticancer drug of paclitaxel (PTX). 4-br-PEG-NH2, FA, and PTX were
      attached to PEG-functionalized nGO (pGO) through a combined chemical and physical
      force to form a nanosized complex, pGO-FA-PTX, defined as the nanodrug system.
      WST-8 assay in vitro illustrated that pGO-FA-PTX inhibited A2780 cells in a
      concentration-dependent manner. Cell viability was kept high to 60% when treated
      with 200 nM of free PTX. However, pGO-FA-PTX with the same dose of PTX (cell
      viability less than 30%) had double the cytotoxicity effect compared to free PTX.
      Furthermore, fluorescence observation demonstrated that pGO-FA-PTX exhibited an
      improved efficiency in killing A2780 cells due to the special affinity between FA
      and FA receptor, which has high expression in cancer cells. The strategy and
      method used in this study could be effective in improving both the
      bioavailability of PTX and therapy efficiency.

PMID- 30221220
TI  - Bomba Rice Conservation with a Natural Biofilm.
AB  - The chemical composition of commercial Syzygium aromaticum, Cinnamomum verum, and
      Laurus nobilis essential oils as well as their antifungal activity against four
      pathogenic fungi isolated from Mediterranean rice grains has been investigated.
      Eighty nine compounds accounting for between 98.5 and 99.4% of the total
      essential oil were identified. The phenylpropanoids eugenol (89.37 +/- 0.29%) and
      eugenol (56.34 +/- 0.41%), followed by eugenol acetate (19.48 +/- 0.13%) were,
      respectively, the main compounds in clove and cinnamon essential oils, whereas
      large amounts of the oxygenated monoterpenes 1,8-cineole (58.07 +/- 0.83%) and
      alpha-terpinyl acetate (13.05 +/- 0.44%) were found in bay leaf essential oil.
      Clove and cinnamon oils showed the best antifungal activity results against all
      tested fungi. Against Alternaria alternata, clove essential oil displayed the
      best antifungal effect, whereas against Curvularia hawaiiensis, cinnamon
      essential oil was more active. Both essential oils showed a similar antifungal
      effect towards Fusarium proliferatum and Fusarium oxysporum. In vitro studies in
      inoculated rice grains showed that clove and cinnamon totally inhibited
      pathogenic fungal development after 30 days of incubation. In vivo studies showed
      that eugenol used with a polysaccharide such as agar-agar formed a fine coat
      which wraps the inoculated rice grains, creating a natural biofilm and reducing
      the development of all pathogenic fungi (80-95%) for 30 days.

PMID- 30221219
TI  - Stimulatory Effects of Methyl-beta-cyclodextrin on Spiramycin Production and
      Physical-Chemical Characterization of Nonhost@Guest Complexes.
AB  - Spiramycin is a macrolide antibiotic and antiparasitic that is used to treat
      toxoplasmosis and various other infections of soft tissues. In the current study,
      we evaluated the effects of alpha-cyclodextrin, beta-cyclodextrin, or methyl-beta
      cyclodextrin supplementation to a synthetic culture medium on biomass and
      spiramycin production by Streptomyces ambofaciens ATCC 23877. We found a high
      stimulatory effect on spiramycin production when the culture medium was
      supplemented with 0.5% (w/v) methyl-beta-cyclodextrin, whereas alpha-cyclodextrin
      or beta-cyclodextrin weakly enhanced antibiotic yields. As the stimulation of
      antibiotic production could be because of spiramycin complexation with
      cyclodextrins with effects on antibiotic stability and/or efflux, we analyzed the
      possible formation of complexes by physical-chemical methods. The results of Job
      plot experiment highlighted the formation of a nonhost@guest complex methyl-beta
      cyclodextrin@spiramycin I in the stoichiometric ratio of 3:1 while they excluded
      the formation of complex between spiramycin I and alpha- or beta-cyclodextrin.
      Fourier-transform infrared spectroscopy measurements were then carried out to
      characterize the methyl-beta-cyclodextrin@spiramycin I complex and individuate
      the chemical groups involved in the binding mechanism. These findings may help to
      improve the spiramycin fermentation process, providing at the same time a new
      device for better delivery of the antibiotic at the site of infection by methyl
      beta-cyclodextrin complexation, as it has been well-documented for other
      bioactive molecules.

PMID- 30221221
TI  - Effects of RNA Splicing Inhibitors on Amyloid Precursor Protein Expression.
AB  - U1 small ribonucleoproteins demonstrate proteopathy in Alzheimer's disease, and
      their inhibition modulates the expression of the amyloid precursor protein (APP).
      We sought to determine whether this effect on the APP expression is a universal
      result of different kinds of RNA splicing inhibitions. We treated cells with two
      chemical RNA splicing inhibitors: isoginkgetin (IGK) and spliceostatin A (SSA),
      in which SSA reduced the APP expression, whereas IGK substantially increased it.
      The following western blot and reverse transcription polymerase chain reaction
      analyses showed that the APP expression under the IGK treatment has distinct
      protein forms, but the total mRNA level was nearly unchanged despite a slight
      switch within its three major transcripts. Further analysis revealed that the APP
      increasing effect of IGK depended on protein translation and might involve
      inhibition in the degradation system. By immunocytochemistry, the APP likely
      redistributed from Golgi to endoplasmic reticulum (ER) in cells treated with IGK.
      When compared to the well-characterized ER-to-Golgi transport inhibitor brefeldin
      A, IGK showed similar APP expression patterns on the western blot. In summary, we
      not only determined the diverse effects of RNA splicing inhibition on the APP
      expression but also found the additional function of IGK on protein subcellular
      traffic.

PMID- 30221222
TI  - Self-Calibration Phenomenon for Near-Infrared Clinical Measurements: Theory,
      Simulation, and Experiments.
AB  - An irradiated turbid medium scatters the light in accordance to its optical
      properties. Near-infrared (NIR) clinical methods, which are based on spectral
      dependent absorption, suffer from an inherent error due to spectral-dependent
      scattering. We present here a unique spatial point, that is, iso-pathlength (IPL)
      point, on the surface of a tissue at which the intensity of re-emitted light
      remains constant. This scattering-indifferent point depends solely on the medium
      geometry. On the basis of this natural phenomenon, we suggest a novel optical
      method for self-calibrated clinical measurements. We found that the IPL point
      exists in both cylindrical and semi-infinite tissue geometries (Supporting
      Information, Video file). Finally, in vivo human finger and mice measurements are
      used to validate the crossing point between the intensity profiles of two
      wavelengths. Hence, measurements at the IPL point yield an accurate absorption
      assessment while eliminating the scattering dependence. This finding can be
      useful for oxygen saturation determination, NIR spectroscopy,
      photoplethysmography measurements, and a wide range of optical sensing methods
      for physiological aims.

PMID- 30221223
TI  - Self-Assembly of Au@Ag Nanoparticles on Mussel Shell To Form Large-Scale 3D
      Supercrystals as Natural SERS Substrates for the Detection of Pathogenic
      Bacteria.
AB  - Herein, we developed a natural surface-enhanced Raman scattering (SERS) substrate
      based on size-tunable Au@Ag nanoparticle-coated mussel shell to form large-scale
      three-dimensional (3D) supercrystals (up to 10 cm2) that exhibit surface
      laminated structures and crossed nanoplates and nanochannels. The high content of
      CaCO3 in the mussel shell results in superior hydrophobicity for analyte
      enrichment, and the crossed nanoplates and nanochannels provided rich SERS hot
      spots, which together lead to high sensitivity. Finite-difference time-domain
      simulations showed that nanoparticles in the channels exhibit apparently a higher
      electromagnetic field enhancement than nanoparticles on the platelets. Thus,
      under optimized conditions (using Au@AgNPs with 5 nm shell thickness), highly
      sensitive SERS detection with a detection limit as low as 10-9 M for rhodamine 6G
      was obtained. Moreover, the maximum electromagnetic field enhancement of
      different types of 3D supercrystals shows no apparent difference, and Au@AgNPs
      were uniformly distributed such that reproducible SERS measurements with a 6.5%
      variation (613 cm-1 peak) over 20 spectra were achieved. More importantly, the as
      prepared SERS substrates can be utilized for the fast discrimination of
      Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa by
      discriminant analysis. This novel Au@Ag self-assembled mussel shell template
      holds considerable promise as low-cost, durable, sensitive, and reproducible
      substrates for future SERS-based biosensors.

PMID- 30221224
TI  - Highly Potent, Stable, and Selective Dimeric Hetarylpropylguanidine-Type
      Histamine H2 Receptor Agonists.
AB  - On the basis of the long-known prototypic pharmacophore 3-(1H-imidazol-4
      yl)propylguanidine (SK&F 91486, 2), monomeric, homodimeric, and heterodimeric
      bisalkylguanidine-type histamine H2 receptor (H2R) agonists with various alkyl
      spacers were synthesized. Aiming at increased H2R selectivity of the ligands, the
      imidazol-4-yl moiety was replaced by imidazol-1-yl, 2-aminothiazol-5-yl or 2
      amino-4-methylthiazol-5-yl according to a bioisosteric approach. All compounds
      turned out to be partial or full agonists at the h/gp/rH2R. The most potent
      analogue, the thiazole-type heterodimeric ligand 63 (UR-Po461), was a partial
      agonist (Emax = 88%) and 250 times more potent than histamine (pEC50: 8.56 vs
      6.16, gpH2R, atrium). The homodimeric structures 56 (UR-Po395) and 58 (UR-Po448)
      exhibited the highest hH2R affinities (pKi: 7.47, 7.33) in binding studies.
      Dimeric amino(methyl)thiazole derivatives, such as 58, generated an increased
      hH2R selectivity compared to the monomeric analogues, e.g., 139 (UR-Po444).
      Although monomeric ligands showed up lower affinities and potencies at the H2R,
      compounds with a short alkylic side chain like 129 (UR-Po194) proved to be highly
      affine hH4R ligands.

PMID- 30221226
TI  - Chalcones and Five-Membered Heterocyclic Isosteres Bind to Alpha Synuclein
      Fibrils in Vitro.
AB  - A series of chalcone and heterocyclic isosteres, in which the enone moiety was
      replaced with an isoxazole and pyrazole ring system, was synthesized and their
      affinities for alpha synuclein (Asyn), amyloid beta (Abeta), and tau fibrils were
      measured in vitro. The compounds were found to have a modest affinity and
      selectivity for Asyn versus Abeta fibrils and low affinity for tau fibrils.
      Insertion of a double bond to increase the extendable surface area resulted in an
      increase in affinity and improvement in selectivity for Asyn versus Abeta and tau
      fibrils. The results of this study indicate that compound 11 is a secondary lead
      compound for structure-activity relationship studies aimed at identifying a
      suitable compound for positron emission tomography-imaging studies of insoluble
      Asyn aggregates in Parkinson's disease.

PMID- 30221225
TI  - Structure and Function of Stony Coral Intraskeletal Polysaccharides.
AB  - Polysaccharides represent a main weight fraction of the intraskeletal organic
      matrix of corals, but their structure, as well as their function in the
      calcification process, has been poorly investigated. This communication shows by
      a combination of techniques (nuclear magnetic resonance, Fourier transform
      infrared, and monosaccharide composition) that their key component is a 1->3 beta
      d glucuronic acid polymer and evidences its influence in vitro in the
      calcification process.

PMID- 30221227
TI  - Phosphatase CDC25B Inhibitors Produced by Basic Alumina-Supported One-Pot Gram
      Scale Synthesis of Fluorinated 2-Alkylthio-4-aminoquinazolines Using Microwave
      Irradiation.
AB  - An efficient, environmentally benign, and inexpensive procedure has been
      developed for the synthesis of fluorinated 2-alkylthio-4-aminoquinazolines by
      microwave irradiation using basic alumina as a solid-support agent as well as a
      solid base. Notably, this protocol features improved energy efficiency, broad
      isothiourea substrate scope, easily available starting materials, and high atom
      efficiency and applicability toward gram-scale synthesis. Additionally, the
      target compounds were evaluated for the cytotoxic effect against human colon
      adenocarcinoma (HCT116 and HT29), human gastric cancer (SGC-7901), human lung
      adenocarcinoma (A549), and human hepatocyte carcinoma (HepG2) cells, and it was
      found that these compounds have excellent antitumor activities. Among them,
      compound 3e was found to be one of the most potent derivatives with IC50 values
      lower than 9.44 MUM against five human tumor cell lines, making it more active
      than cisplatin (DDP). Furthermore, for the first time, the fluorinated 2
      alkylthio-substituted 4-aminoquinazolines were identified as phosphatase CDC25B
      inhibitors.

PMID- 30221228
TI  - Accurate Monitoring of Renal Injury State through in Vivo Magnetic Resonance
      Imaging with Ferric Coordination Polymer Nanodots.
AB  - It is highly challenging to detect the pathophysiology of the diseased kidneys
      and achieve precise diagnosis because there are few in vivo noninvasive imaging
      techniques to quantitatively assess kidney dysfunction. This longstanding
      challenge is normally attributed to the limited molecular contrast agents which
      can be addressed with renal clearable nanoprobes. In this report, we demonstrate
      the use of magnetic resonance imaging along with renal clearable ferric
      coordination polymer nanodots (Fe-CPNDs) for in vivo monitoring the kidney
      dysfunction effects following drug (daunomycin)-induced kidney injury. After
      intravenous injection of Fe-CPNDs, the change of the MR signal in the kidney can
      be precisely correlated with local pathological lesion which is demonstrated by
      renal anatomic details and biochemical examinations of urine and blood. This
      finding opens the door to the possibility of noninvasively assessing kidney
      dysfunction and local injuries.

PMID- 30221229
TI  - Surface Engineering of Gold Nanorods for Cytochrome c Bioconjugation: An
      Effective Strategy To Preserve the Protein Structure.
AB  - The surface of gold nanorods (Au NRs) has been appropriately engineered to
      achieve a suitable interface for bioconjugation with horse heart cytochrome c
      (HCc). HCc, an extensively studied and well-characterized protein, represents an
      ideal model for nanoparticle (NP)-protein conjugation studies because of its
      small size, high stability, and commercial availability. Here, the native state
      of the protein has been demonstrated for the first time, by means of Raman
      spectroscopy, to be retained upon conjugation with the anisotropic Au
      nanostructures, thus validating the proposed protocol as specifically suited to
      mostly preserve the plasmonic properties of the NRs and to retain the structure
      of the protein. The successful creation of such bioconjugates with the retention
      of the protein structure and function along with the preservation of the NP
      properties represents a challenging but essential task, as it provides the only
      way to access functional hybrid systems with potential applications in
      biotechnology, medicine, and catalysis. In this perspective, the organic capping
      surrounding the Au NRs plays a key role, as it represents the functional
      interface for the conjugation step. Cetyltrimethylammonium bromide-coated Au NRs,
      prepared by using a seed-mediated synthetic route, have been wrapped with
      polyacrylic acid (PAA) by means of electrostatic interactions following a layer
      by-layer approach. The resulting water-dispersible negatively charged AuNRs@PAA
      NPs have then been electrostatically bound to the positively charged HCc. The
      bioconjugation procedure has been thoroughly monitored by the combined analysis
      of UV-vis absorption, resonance Raman and Fourier transform infrared
      spectroscopies, transmission electron microscopy microscopy, and zeta-potential,
      which verified the successful conjugation of the protein to the nanorods.

PMID- 30221230
TI  - Small Cationic Peptides: Influence of Charge on Their Antimicrobial Activity.
AB  - The first stage of the action mechanism of small cationic peptides with
      antimicrobial activity is ruled by electrostatic interactions between the peptide
      and the pathogen cell membrane. Thus, an increase in its activity could be
      expected with an increase in the positive charge on the peptide. By contrast, the
      opposite behavior has been observed when the charge increases to reach a critical
      value, beyond which the activity falls. This work studies the perturbation
      effects in a cell membrane model for two small cationic peptides with similar
      length and morphology but with different cationic charges. The synthesis and
      antibacterial activity of the two peptides used in this study are described. The
      thermodynamic study associated with the insertion of these peptides into the
      membrane and the perturbing effects on the bilayer structure provide valuable
      insights into the molecular action mechanism associated with the charge of these
      small cationic peptides.

PMID- 30221231
TI  - Pillars of Life: Is There a Relationship between Lifestyle Factors and the
      Surface Characteristics of Dragonfly Wings?
AB  - Dragonfly wings are of great interest to researchers investigating biomimetic
      designs for antiwetting and antibacterial surfaces. The waxy epicuticular layer
      on the membrane of dragonfly wings possesses a unique surface nanoarchitecture
      that consists of irregular arrays of nanoscale pillars. This architecture confers
      superhydrophobic, self-cleaning, antiwetting, and antibiofouling behaviors. There
      is some evidence available that suggests that lifestyle factors may have
      influenced the evolution of the wing nanostructures and, therefore, the resulting
      properties of the wings; however, it appears that no systematic studies have been
      performed that have compared the wing surface features across a range of
      dragonfly species. Here, we provided a comparison of relevant wing surface
      characteristics, including chemical composition, wettability, and
      nanoarchitecture, of seven species of dragonfly from three families including
      Libellulidae, Aeshnidae, and Gomphidae. The characteristic nanopillar arrays were
      found to be present, and the chemical composition and the resultant wing surface
      superhydrophobicity were found to be well-conserved across all of the species
      studied. However, subtle differences were observed between the height, width, and
      density of nanofeatures and water droplet bouncing behavior on the wing surfaces.
      The results of this research will contribute to an understanding of the physical
      and chemical surface features that are optimal for the design of antiwetting and
      antibacterial surfaces.

PMID- 30221232
TI  - Indolyl-Pyridinyl-Propenone-Induced Methuosis through the Inhibition of PIKFYVE.
AB  - Methuosis is a form of nonapoptotic cell death characterized by the accumulation
      of macropinosome-derived vacuoles. Herein, we identify PIKFYVE, a class III
      phosphoinositide (PI) kinase, as the protein target responsible for the methuosis
      inducing activity of indolyl-pyridinyl-propenones (3-(5-methoxy-2-methyl-1H-indol
      3-yl)-1-(4-pyridinyl)-2-propen-1-one). We further characterize the effects of
      chemical substitutions at the 2- and 5-indolyl positions on cytoplasmic
      vacuolization and PIKFYVE binding and inhibitory activity. Our study provides a
      better understanding of the mechanism of methuosis-inducing indolyl-pyridinyl
      propenones.

PMID- 30221233
TI  - Copper-Catalyzed Syntheses of Pyrene-Pyrazole Pharmacophores and Structure
      Activity Studies for Tubulin Polymerization.
AB  - Tubulin polymerization is critical in mitosis process, which regulates
      uncontrolled cell divisions. Here, we report a new class of pyrene-pyrazole
      pharmacophore (PPP) for targeting microtubules. Syntheses of seven pyrenyl
      substituted pyrazoles with side-chain modification at N-1 and C-3 positions of
      the pyrazole ring were accomplished from alkenyl hydrazones via C-N
      dehydrogenative cross-coupling using copper catalyst under aerobic condition.
      Tubulin polymerization with PPPs was investigated using docking and biological
      tools to reveal that these ligands are capable of influencing microtubule
      polymerization and their interaction with alpha-, beta-tubulin active binding
      sites, which are substituent specific. Furthermore, cytotoxicity response of
      these PPPs was tested on cancer cells of different origin, such as MCF-7, MDA
      MB231, and C32, and also noncancerous normal cells, such as MCF-10A. All newly
      synthesized PPPs showed excellent anticancer activities. The anticancer
      activities and half-maximal inhibitory concentration (IC50) values of all PPPs
      across different cancer cell lines (MCF-7, MDA-MB231, and C32) have been
      demonstrated. 1,3-Diphenyl-5-(pyren-1-yl)-1H-pyrazole was found to be best among
      all other PPPs in killing significant population of all of the cancerous cell
      with IC50 values 1 +/- 0.5, 0.5 +/- 0.2, and 5.0 +/- 2.0 MUM in MCF-7, MDA-MB231,
      and C32 cells, respectively.

PMID- 30221234
TI  - Virtual Screening of Chemical Compounds for Discovery of Complement C3 Ligands.
AB  - The complement system is our first line of defense against foreign pathogens, but
      when it is not properly regulated, complement is implicated in the pathology of
      several autoimmune and inflammatory disorders. Compstatin is a peptidic
      complement inhibitor that acts by blocking the cleavage of complement protein C3
      to the proinflammatory fragment C3a and opsonin fragment C3b. In this study, we
      aim to identify druglike small-molecule complement inhibitors with
      physicochemical, geometric, and binding properties similar to those of
      compstatin. We employed two approaches using various high-throughput virtual
      screening methods, which incorporate molecular dynamics (MD) simulations,
      pharmacophore model design, energy calculations, and molecular docking and
      scoring. We have generated a library of 274 chemical compounds with
      computationally predicted binding affinities for the compstatin binding site of
      C3. We have tested subsets of these chemical compounds experimentally for
      complement inhibitory activity, using hemolytic assays, and for binding affinity,
      using microscale thermophoresis. As a result, although none of the compounds
      showed inhibitory activity, compound 29 was identified to exhibit weak
      competitive binding against a potent compstatin analogue, therefore validating
      our computational approaches. Additional docking and MD simulation studies
      suggest that compound 29 interacts with C3 residues, which have been shown to be
      important in binding of compstatin to the C3c fragment of C3. Compound 29 is
      amenable to physicochemical optimization to acquire inhibitory properties.
      Additionally, it is possible that some of the untested compounds will demonstrate
      binding and inhibition in future experimental studies.

PMID- 30221235
TI  - Analysis of the Binding of Expansin Exl1, from Pectobacterium carotovorum, to
      Plant Xylem and Comparison to EXLX1 from Bacillus subtilis.
AB  - The plant xylem is a preferred niche for some important bacterial phytopathogens,
      some of them encoding expansin proteins, which bind plant cell walls. Yet, the
      identity of the substrate for bacterial expansins within the plant cell wall and
      the nature of its interaction with it are poorly known. Here, we determined the
      localization of two bacterial expansins with differing isoelectric points (and
      with differing binding patterns to cell wall extracts) on plant tissue through in
      vitro fluorophore labeling and confocal imaging. Differential localization was
      observed, in which Exl1 from Pectobacterium carotovorum located into the
      intercellular spaces between xylem vessels and adjacent cells of the plant xylem,
      whereas EXLX1 from Bacillus subtilis bound cell walls of most cell types. In
      isolated vascular tissue, however, both PcExl1 and BsEXLX1 preferentially bound
      to tracheary elements over the xylem fibers, even though both are composed of
      secondary cell walls. Fluorescence correlation spectroscopy, employed to analyze
      the interaction of expansins with isolated xylem, indicates that binding is
      governed by more than one factor, which could include interaction with more than
      one type of polymer in the fibers, such as cellulose and hemicellulose or pectin.
      Binding to different polysaccharides could explain the observed reduction of
      cellulolytic and xylanolytic activities in the presence of expansin, possibly
      because of competition for the substrate. Our findings are relevant for the
      comprehensive understanding of the pathogenesis by P. carotovorum during xylem
      invasion, a process in which Exl1 might be involved.

PMID- 30221236
TI  - [Ag(L)NO3] Complexes with 2-Benzoylpyridine-Derived Hydrazones: Cytotoxic
      Activity and Interaction with Biomolecules.
AB  - Complexes [Ag(H2BzPh)NO3] (1), [Ag(H2BzpCH3Ph)NO3] (2), [Ag(H2BzpClPh)NO3] (3),
      and [Ag(H2BzpNO2Ph)NO3] (4) were synthesized with 2-benzoylpyridine
      benzoylhydrazone (H2BzPh) and its para-methyl-benzoylhydrazone (H2BzpCH3Ph), para
      chloro-benzoylhydrazone (H2BzpClPh), and para-nitro-benzoylhydrazone (H2BzpNO2Ph)
      derivatives. Experimental data indicate that the nitrate ligand binds more
      strongly to the silver center through one of the oxygen atoms, whereas the second
      oxygen atom from nitrate and the hydrazone oxygen makes much weaker interactions
      with the metal. Dissociation of nitrate most probably occurs in solution and in
      biological media. Interestingly, theoretical calculations suggested that when
      dissociation of the nitrate takes place, all bond orders involving the metal and
      the atoms from the hydrazone ligand increase significantly, showing that the
      bonding of nitrate results in the weakening of all other interactions in the
      metal coordination sphere. Upon complexation of the hydrazones to silver(I),
      cytotoxicity against B16F10 metastatic murine melanoma cells increased in all
      cases. Complexes (1-3) proved to be more cytotoxic than cisplatin. All compounds
      were more cytotoxic to B16F10 cells than to nontumorigenic murine Melan-A
      melanocyte cells. Interestingly, the selectivity index (SI = IC50 non-malignant
      cells/IC50 tumor cells) of complex (1), SI = 23, was much higher than that of the
      parent hydrazone ligand, SI = 9.5. Studies on the interactions of complexes (1-3)
      with DNA suggested that although (1-3) interact with calf thymus DNA by an
      intercalative mode, direct covalent binding of silver(I) to DNA probably does not
      occur. Complexes (1-3) interact in vitro with human serum albumin indicating that
      these compounds could be transported by albumin.

PMID- 30221237
TI  - Controlled Dye Aggregation in Sodium Dodecylsulfate-Stabilized
      Poly(methylmethacrylate) Nanoparticles as Fluorescent Imaging Probes.
AB  - Polymer nanoparticles are used extensively in biomedical applications.
      Poly(methylmethacrylate) (PMMA) nanoparticles obtained via nanoprecipitation were
      unstable and flocculate or precipitate from solution within a few hours. A simple
      method to improve the stability of the particles using surfactants at low
      concentrations was carried out to produce PMMA nanoparticles with long-term
      stability in water (>6 months). The increased stability was attributed to the
      incorporation of surfactants inside the polymer particles during
      nanoprecipitation. The same methodology was also adopted to encapsulate a highly
      fluorescent hydrophobic perylene tetraester inside the polymer nanoparticles with
      good stability in water. Because of the presence of the anionic sodium dodecyl
      sulfate, the particles showed a negative zeta potential of -34.7 mV and an
      average size of 150 nm. Similarly, the dye-encapsulated polymer nanoparticles
      showed a zeta potential of -35.1 mV and an average particle size of 180 nm. By
      varying the concentration of encapsulated dyes inside the polymer nanoparticles,
      dye aggregation could be controlled, and the fluorescence profiles of the
      nanoparticles were altered. To understand the uptake and toxicity of the polymer
      nanoparticles, baby hamster kidney cells were chosen as a model system. The
      polymer nanoparticles were taken up by the cells within 3 h and were nontoxic at
      concentrations as high as 100 ppm. The confocal micrographs of the cells revealed
      localized fluorescence from the polymer nanoparticles around the nucleus in the
      cytoplasm without the penetration of the nuclear envelope.

PMID- 30221238
TI  - Protein Fibril-Templated Biomimetic Synthesis of Highly Fluorescent Gold
      Nanoclusters and Their Applications in Cysteine Sensing.
AB  - Biomimetic synthesis of multifunctional fluorescent gold nanoclusters (Au NCs) is
      of great demand because of their ever-increasing applications. In this study, we
      have used self-assembled bovine serum albumin (BSA) amyloid-like nanofibers as
      the bioinspired scaffold for the synthesis of Au NCs. The amyloid fibril
      stabilized gold nanocluster (Fib-Au NC) has been found to have appreciable
      enhancement of fluorescence emission and a large 25 nm red shift in its emission
      maxima when compared to its monomeric protein counterpart (BSA-Au NC). The
      underlying mechanism accountable for the fluorescence behavior and its spectral
      shift has been thoroughly investigated by a combined use of spectroscopic and
      microscopic techniques. We have subsequently demonstrated the use of Fib-Au NCs
      for cysteine (Cys) sensing both in vitro and inside live cells. Additionally,
      cellular uptake and postpermeation effect of Fib-Au NCs have also been
      ascertained by detailed flow cytometry analysis, viability assay, and real-time
      apoptotic gene expression profiling.

PMID- 30221239
TI  - Plasmid-Based One-Pot Saturation Mutagenesis and Robot-Based Automated Screening
      for Protein Engineering.
AB  - We evaluated a method for protein engineering using plasmid-based one-pot
      saturation mutagenesis and robot-based automated screening. When the biases in
      nucleotides and amino acids were assessed for a loss-of-function point mutation
      in green fluorescent protein, the ratios of gain-of-function mutants were not
      significantly different from the expected values for the primers among the three
      different suppliers. However, deep sequencing analysis revealed that the ratios
      of nucleotides in the primers were highly biased among the suppliers. Biases for
      NNB were less severe than for NNN. We applied this method to screen a fusion
      protein of two chitinases, ChiA and ChiB (ChiAB). Three NNB codons as well as
      tyrosine and serine (X1YSX2X3) were inserted to modify the surface structure of
      ChiAB. We observed significant amino acid bias at the X3 position in water
      soluble, active ChiAB-X1YSX2X3 mutants. Examination of the crystal structure of
      one active mutant, ChiAB-FYSFV, revealed that the X3 residue plays an important
      role in structure stabilization.

PMID- 30221240
TI  - Influence of Cobalt Ions on Collagen Gel Formation and Their Interaction with
      Osteoblasts.
AB  - Metals on metal implants have long been used in arthroplasties because of their
      robustness and low dislocation rate. Several relatively low-corrosion metals have
      been used in arthroplasty, including 316L stainless steel, titanium, and cobalt
      chromium-molybdenum alloy. Debris from these implants, however, has been found to
      cause inflammatory responses leading to unexpected failure rates approaching 10%
      7 years surgery. Safety assessment of these materials traditionally relies on the
      use of simple two-dimensional assays, where cells are grown on the surface of the
      material over a relatively short time frame. It is now well-known that the
      composition and stiffness of the extracellular matrix (ECM) have a critical
      effect on cell function. In this work, we have evaluated how cobalt ions
      influence the assembly of type I collagen, the principle component of the ECM in
      bone. We found that cobalt had a significant effect on collagen matrix formation,
      and its presence results in local variations in collagen density. This increase
      in heterogeneity causes an increase in localized mechanical properties but a
      decrease in the bulk stiffness of the material. Moreover, when collagen matrices
      contained cobalt ions, there was a significant change in how the cells interacted
      with the collagen matrix. Fluorescence images and biological assays showed a
      decrease in cell proliferation and viability with an increase in cobalt
      concentration. We present evidence that the cobalt ion complex interacts with the
      hydroxyl group present in the carboxylic terminal of the collagen fibril,
      preventing crucial stabilizing bonds within collagen formation. This demonstrates
      that the currently accepted toxicity assays are poor predictors of the longer
      term biological performance of a material.

PMID- 30221241
TI  - Highly Sensitive Ratiometric Chemosensor and Biomarker for Cyanide Ions in the
      Aqueous Medium.
AB  - A newly designed cyanide-selective chemosensor based on chromone containing
      benzothiazole groups [3-(2,3-dihydro-benzothiazol-2-yl)-chromen-4-one (DBTC)] was
      synthesized and structurally characterized by physico-chemical, spectroscopic,
      and single-crystal X-ray diffraction analyses. The compound DBTC can detect
      cyanide anions based on nucleophilic addition as low as 5.76 nM in dimethyl
      sulfoxide-N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid buffer (20 mM, pH
      7.4) (v/v = 1:3). The binding mode between receptor DBTC and cyanide nucleophile
      has also been demonstrated by experimental studies using various spectroscopic
      tools and theoretical studies, and the experimental work has also been verified
      by characterizing one supporting compound of similar probable structure of the
      final product formed between DBTC and cyanide ion (DBTC-CN compound) by single
      crystal X-ray analysis for detailed structural analyses. In theoretical study,
      density functional theory procedures have been used to calculate the molecular
      structure and the calculation of the Fukui function for evaluation of the
      electrophilic properties of each individual acceptor atom. Furthermore, the
      efficacy of the probe (DBTC) to detect the distribution of CN- ions in living
      cells has been checked by acquiring the fluorescence image using a confocal
      microscope. Notably, the paper strips with DBTC were prepared, and these could
      serve as efficient and suitable CN- test kits successfully.

PMID- 30221242
TI  - Classification of ADNI PET Images via Regularized 3D Functional Data Analysis.
AB  - We propose a penalized Haar wavelet approach for the classification of 3D brain
      images in the framework of functional data analysis, which treats each entire 3D
      brain image as a single functional input thus automatically takes into account
      the spatial correlations of voxel level imaging measures. We validate the
      proposed approach through extensive simulations and compare its classification
      performance with other commonly used machine learning methods, which show that
      the proposed method outperforms other methods in both classification accuracy and
      identification of the relevant voxels. We then apply the proposed method to the
      practical classification problems for Alzheimer's disease using PET images
      obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to
      highlight the advantages of our approach.

PMID- 30221243
TI  - A Clinically-Relevant Dose of Methylphenidate Enhances Synaptic Inhibition in the
      Juvenile Rat Prefrontal Cortex.
AB  - Methylphenidate (MPH) is perhaps the most commonly prescribed psychoactive
      substance for young children and adolescents; however, its effects on the
      immature brain are not well understood. MPH is increasingly abused by adolescents
      and prescriptions are being issued to increasingly younger children without
      rigorous psychological testing, raising the potential for misdiagnosis; it is
      therefore crucial to understand how this drug might impact a healthy, developing
      brain. Recently, we have shown that a clinically-relevant dose of MPH depresses
      the activity of pyramidal neurons in the prefrontal cortex of normal juvenile
      rats, but its effects on inhibitory synaptic transmission remain to be explored.
      We therefore recorded spontaneous (s), miniature (m), and evoked (e) inhibitory
      postsynaptic currents (IPSCs) in layer 5 pyramidal neurons in juvenile rat
      prefrontal cortex. We found a dose-dependent effect of MPH on sIPSC frequency but
      not amplitude, where 0.3 mg/kg significantly decreased frequency, but 1 mg/kg
      significantly increased frequency. Moreover, mIPSCs were not affected by either
      dose of MPH, whereas the amplitudes, as well as paired-pulse ratios and
      coefficient of variations of evoked IPSCs were significantly increased after MPH
      treatment, indicating a presynaptic action. Tonic GABA current was also not
      affected by MPH treatment. Taken together, these results suggest that MPH
      administration to a healthy juvenile may enhance excitation of GABAergic
      interneurons; thus shifting the excitation-inhibition balance in the prefrontal
      cortex towards inhibition, and depressing overall prefrontal cortical activity.
      Our findings also indicate that the adolescent brain is more sensitive to MPH
      than previously thought, and dose ranges need to be reconsidered for age as well
      as size.

PMID- 30221245
TI  - Measuring the mismatch between field of study and occupation using a task-based
      approach.
AB  - This paper seeks to provide a continuous measure to represent the distance
      between skills acquired in tertiary education and those required in an
      individual's occupation. This distance measure, which is computed by combining
      data from the 2010 Brazilian census with information from the 2010 Brazilian
      classification of occupations, suggests that workers usually classified in most
      of the literature into a single group of mismatches are in fact quite
      heterogeneous in the way their occupations are associated with areas of study.
      Evidence also shows that, even among mismatched workers, hourly labor earnings
      tend to decrease as the distance measure increases. This indicates the labor
      earnings penalty is not the same for all mismatched workers, seemingly changing
      substantially depending on the level of similarity between occupation and field
      of study.

PMID- 30221244
TI  - The Benefits and Challenges of Implementing Motivational Features to Boost
      Cognitive Training Outcome.
AB  - In the current literature, there are a number of cognitive training studies that
      use N-back tasks as their training vehicle; however, the interventions are often
      bland, and many studies suffer from considerable attrition rates. An increasingly
      common approach to increase participant engagement has been the implementation of
      motivational features in training tasks; yet, the effects of such "gamification"
      on learning have been inconsistent. To shed more light on those issues, here, we
      report the results of a training study conducted at two Universities in Southern
      California. A total of 115 participants completed 4 weeks (20 sessions) of N-back
      training in the laboratory. We varied the amount of "gamification" and the
      motivational features that might make the training more engaging and,
      potentially, more effective. Thus, 47 participants trained on a basic
      color/identity N-back version with no motivational features, whereas 68
      participants trained on a gamified version that translated the basic mechanics of
      the N-back task into an engaging 3D space-themed "collection" game (Deveau et al.
      Frontiers in Systems Neuroscience, 8, 243, 2015). Both versions used similar
      adaptive algorithms to increase the difficulty level as participants became more
      proficient. Participants' self-reports indicated that the group who trained on
      the gamified version enjoyed the intervention more than the group who trained on
      the non-gamified version. Furthermore, the participants who trained on the
      gamified version exerted more effort and also improved more during training.
      However, despite the differential training effects, there were no significant
      group differences in any of the outcome measures at post-test, suggesting that
      the inclusion of motivational features neither substantially benefited nor hurt
      broader learning. Overall, our findings provide guidelines for task
      implementation to optimally target participants' interest and engagement to
      promote learning, which may lead to broader adoption and adherence of cognitive
      training.

PMID- 30221247
TI  - Hepatobiliary-Specific Contrast Agent in Biliary Leak.

PMID- 30221248
TI  - Understanding the impact of neoadjuvant chemoradiation on health-related quality
      of life in esophageal cancer.

PMID- 30221246
TI  - Network Approaches to Understand Individual Differences in Brain Connectivity:
      Opportunities for Personality Neuroscience.
AB  - Over the past decade, advances in the interdisciplinary field of network science
      have provided a framework for understanding the intrinsic structure and function
      of human brain networks. A particularly fruitful area of this work has focused on
      patterns of functional connectivity derived from non-invasive neuroimaging
      techniques such as functional magnetic resonance imaging (fMRI). An important
      subset of these efforts has bridged the computational approaches of network
      science with the rich empirical data and biological hypotheses of neuroscience,
      and this research has begun to identify features of brain networks that explain
      individual differences in social, emotional, and cognitive functioning. The most
      common approach estimates connections assuming a single configuration of edges
      that is stable across the experimental session. In the literature, this is
      referred to as a static network approach, and researchers measure static brain
      networks while a subject is either at rest or performing a cognitively demanding
      task. Research on social and emotional functioning has primarily focused on
      linking static brain networks with individual differences, but recent advances
      have extended this work to examine temporal fluctuations in dynamic brain
      networks. Mounting evidence suggests that both the strength and flexibility of
      time-evolving brain networks influence individual differences in executive
      function, attention, working memory, and learning. In this review, we first
      examine the current evidence for brain networks involved in cognitive
      functioning. Then we review some preliminary evidence linking static network
      properties to individual differences in social and emotional functioning. We then
      discuss the applicability of emerging dynamic network methods for examining
      individual differences in social and emotional functioning. We close with an
      outline of important frontiers at the intersection between network science and
      neuroscience that will enhance our understanding of the neurobiological
      underpinnings of social behavior.

PMID- 30221250
TI  - Sesquiterpene Cyclisations Catalysed inside the Resorcinarene Capsule and
      Application in the Short Synthesis of Isolongifolene and Isolongifolenone.
AB  - Terpenes constitute the largest class of natural products and serve as an
      important source for medicinal treatments. Despite constant progress in chemical
      synthesis, the construction of complex polycyclic sesqui- and diterpene scaffolds
      remains challenging. Natural cyclase enzymes, however, are able to form the whole
      variety of terpene structures from just a handful of linear precursors. Man-made
      catalysts able to mimic such natural enzymes are lacking. Here, we describe the
      examples of sesquiterpene cyclisations inside an enzyme-mimicking supramolecular
      catalyst. This strategy allowed the formation of the tricyclic sesquiterpene
      isolongifolene in only four steps. The mechanism of the catalysed cyclisation
      reaction was elucidated using 13C-labelling studies and DFT calculations.

PMID- 30221249
TI  - Selective and synergistic cobalt(III)-catalyzed three-component C-H bond addition
      to dienes and aldehydes.
AB  - Two-component C-H bond additions to a large variety of coupling partners have
      been developed with applications towards materials, natural product and drug
      synthesis. Sequential three-component C-H bond addition across two different
      coupling partners potentially enables the convergent synthesis of complex
      molecular scaffolds from simple precursors. Here, we report three-component
      Co(III)-catalyzed C-H bond additions to dienes and aldehydes that proceeds with
      high regio- and stereoselectivity resulting in two new carbon-carbon sigma-bonds
      and from four to six new stereocenters. The reaction relies on the synergistic
      reactivity of the diene and aldehyde with neither undergoing C-H bond addition
      alone. A detailed mechanism is supported by X-ray structural characterization of
      a Co(III)-allyl intermediate, observed transfer of stereochemical information,
      and kinetic isotope studies. The applicability of the method to biologically
      relevant molecules is exemplified by the rapid synthesis of the western fragment
      of the complex ionophore antibiotic lasalocid A.

PMID- 30221251
TI  - Peptide Antigen Concentration Modulates Digital NFAT1 Activation in Primary Mouse
      Naive CD8+ T Cells as Measured by Flow Cytometry of Isolated Cell Nuclei.
AB  - Circulating naive T cells exist in a quiescent state. After TCR contact with the
      cognate peptide presented by APCs in secondary lymphoid structures, T cells
      undergo a period of rapid transcriptional changes that set the stage for fate
      determining effector or memory programming. We describe a novel method to analyze
      TCR signaling pathway activation in nuclei isolated from primary mouse naive T
      cells after stimulation with natural peptide Ags. We prelabeled cells with cell
      tracking dye to easily distinguish CD8+ T cell nuclei from APC nuclei by
      conventional flow cytometry. Using this approach, we observed clear digital
      activation of NFAT1 transcription factor in OT-I T cells stimulated with OVA
      peptide presented by bulk splenocytes. OVA concentration had discrete control
      over the fraction of the cells that translocated NFAT1, indicating that a
      distinct threshold amount of TCR signaling is required to switch on NFAT1 in
      naive T cells. This behavior was cell contact dependent and qualitatively more
      exact than the NFAT1 response in ionomycin-stimulated naive T cells. These data
      contribute to our understanding of the digital behavior of TCR signaling
      components documented in other studies and indicate how T cells might
      discriminate log-fold changes in Ag availability during an actual infection.
      Overall, these results highlight the potential of this coculture nuclei isolation
      protocol to address stimulation-dependent translocation of proteins in primary
      lymphocytes.

PMID- 30221252
TI  - When nucleoside chemistry met hypervalent iodine reagents.
AB  - There has been increasing use of hypervalent iodine reagents in the field of
      nucleoside chemistry. Applications span: (a) synthesis of nucleoside analogues
      with sulfur and seleno sugar surrogates, (b) synthesis of unusual carbocyclic and
      ether ring-containing nucleosides, (c) introduction of sulfur and selenium into
      pyrimidine bases of nucleosides and analogues, (d) synthesis of isoxazole and
      isoxazoline ring-containing nucleoside analogues, (e) involvement of purine ring
      nitrogen atoms for remote C-H bond oxidation, and (f) metal-catalyzed and
      uncatalyzed synthesis of benzimidazolyl purine nucleoside analogues by
      intramolecular C-N bond formation. This review offers a perspective on
      developments involving the use of hypervalent iodine reagents in the field of
      nucleoside chemistry that have appeared in the literature in the 2003-2017 time
      frame.

PMID- 30221253
TI  - Development of a High Resolution 3D Infant Stomach Model for Surgical Planning.

PMID- 30221254
TI  - Med-vest: A wearable sensory platform.
AB  - Sickle cell disease is a genetic mutation that causes sickling of the red blood
      cells, affecting between 90,000 and 100,000 Americans. Researchers must develop
      methods of data acquisition capable of maximizing both the amount of data being
      collected and types of data being collected to form the most accurate diagnosis
      and treatment for patients. Popular data acquisition forms are the use of mobile
      phones, sensory systems, and wearable technology. In this paper, we attempt to
      bridge the gap between the three, combining a wearable sensory system with the
      computation and communication power of mobile phones. We propose the application
      of sickle cell disease as a structure around which to design a textile-based data
      acquisition system.

PMID- 30221255
TI  - Automated head motion system improves reliability and lessens operator dependence
      for head impulse testing of vestibular reflexes.
AB  - Deficiency of the eye-stabilizing vestibulo-ocular reflex (VOR) is a defining
      feature in multiple diseases of the vestibular labyrinth, which comprises the
      inner ear's sensors of head rotation, translation and orientation. Diagnosis of
      these disorders is facilitated by observation and measurement of eye movements
      during and after head motion. The video head impulse test has recently garnered
      interest as a clinical diagnostic assessment of vestibular dysfunction. In
      typical practice, it involves use of video-oculography goggles to measure eye
      movements while a clinician examiner grasps the subject's head and manually
      rotates it left or right at sufficient acceleration to cover ~20 deg over ~150
      mS, reaching a peak velocity of >120 deg/S midway through the movement. Manual
      delivery of head impulses incurs significant trial-by-trial, inter-session and
      inter-operator variability, which lessens the test's reliability, efficiency,
      safety and standardization across testing facilities. We describe application of
      a novel, compact and portable automated head impulse test (aHITTM) device that
      delivers highly repeatable head motion stimuli about axes parallel to those of
      the vestibular labyrinth's six semicircular canals, with programmable Gaussian
      and sinusoidal motion profiles at amplitudes, velocities and accelerations
      sufficient to test VOR function over the spectral range for which the VOR
      dominates other vision-stabilizing reflexes. We tested the aHITTM on human
      subjects and demonstrated its high reproducibility compared to manually delivered
      head impulses. This device has the potential to be a valuable clinical and
      research tool for diagnostic evaluation and investigation of the vestibular
      system.

PMID- 30221256
TI  - Modeling Terminologies for Reusability in Faceted Systems.
AB  - We integrate heterogeneous terminologies into our category-theoretic model of
      faceted browsing and show that existing terminologies and vocabularies can be
      reused as facets in a cohesive, interactive system. Commonly found in online
      search engines and digital libraries, faceted browsing systems depend upon one or
      more taxonomies which outline the structure and content of the facets available
      for user interaction. Controlled vocabularies or terminologies are often curated
      externally and are available as a reusable resource across systems. We
      demonstrated previously that category theory can abstractly model faceted
      browsing in a way that supports the development of interfaces capable of reusing
      and integrating multiple models of faceted browsing. We extend this model by
      illustrating that terminologies can be reused and integrated as facets across
      systems with examples from the biomedical domain. Furthermore, we extend our
      discussion by exploring the requirements and consequences of reusing existing
      terminologies and demonstrate how categorical operations can create reusable
      groupings of facets.

PMID- 30221257
TI  - More is not Always Better: An Epidemiological Assessment of Migraine Frequency
      and the Impact on Relationships.
AB  - Objective: Chronic pain negatively impacts spouse/partner relationships, with
      greater impact associated with higher pain severity and co-morbid mood
      disturbance. This study investigated the role of pain episode frequency in
      migraineurs on relationship effects. Methods: An online survey was conducted,
      collecting information about migraine, psychological distress, and relationship
      impact using standardized measures. Adults previously diagnosed with migraine
      were invited to participate through postings on migraine community websites and
      social media. Impact was evaluated based on four migraine frequency categories
      (migraines/month): less than weekly (0-3), one to two episodes weekly (4-9 and 10
      15), and more than twice weekly (>15). Results: A total of 1,399 adult
      migraineurs were included. Spouse/partner relationships had been mildly
      moderately damaged for 30% with 0-3 migraine monthly, increasing to 40% with >15
      migraine monthly. Migraine had contributed to a break-up for 4% with 0-3
      migraines monthly, increasing to 8% for those with >15 migraines monthly. About
      57% of participants reported satisfaction with their current spouse/partner, with
      satisfaction unaffected by migraine frequency among those who were satisfied with
      their partners. Negative impact on relationships with children and close friends
      also increased with migraine frequency. Depression and anxiety were significantly
      correlated with migraine frequency (P<0.001) and modulated relationship impact.
      Conclusion: As migraine frequency increased, negative impact on relationships
      also increased. Interestingly, satisfaction with current spouse/partner was high
      for all migraine frequency categories. Clinically, this suggests that frequent
      migraineurs may benefit from a referral to couples counseling with a therapist
      that specializes in medically ill.

PMID- 30221259
TI  - SAS(r) Macros for Computing Causal Mediated Effects in Two- and Three-Wave
      Longitudinal Models.
AB  - Mediation analysis is a statistical technique for investigating the extent to
      which a mediating variable transmits the effect of an independent variable to a
      dependent variable. Because it is used in many fields, there have been rapid
      developments in statistical mediation. The most cutting-edge statistical
      mediation analysis focuses on the causal interpretation of mediated effects.
      Causal inference is particularly challenging in mediation analysis because of the
      difficulty of randomizing subjects to levels of the mediator. The focus of this
      paper is on updating three existing SAS(r) macros (%TWOWAVEMED,
      %TWOWAVEMONTECARLO, and %TWOWAVEPOSTPOWER, presented at SAS(r) Global Forum 2017)
      in two important ways. First, the macros are updated to incorporate new cutting
      edge methods for estimating longitudinal mediated effects from the Potential
      Outcomes Framework for causal inference. The two new methods are inverse
      propensity weighting, an application of propensity scores, and sequential G
      estimation. The causal inference methods are revolutionary because they frame the
      estimation of mediated effects in terms of differences in potential outcomes,
      which align more naturally with how researchers think about causal inference.
      Second, the macros are updated to estimate mediated effects across three waves of
      data. The combination of these new causal inference methods and three waves of
      data enable researchers to test how causal mediated effects develop and maintain
      over time.

PMID- 30221258
TI  - Diet Modulates Adipose Tissue Oxidative Stress in a Murine Acute Chagas Model.
AB  - Chagas disease, also known as American trypanosomiasis, is a tropical parasitic
      disease caused by the protozoan Trypanosoma cruzi. T. cruzi targets adipose
      tissue, which serves as a reservoir of this parasite. T. cruzi infection of
      adipose tissue is characterized by increased lipolysis, oxidative stress, and
      parasitemia. High fat diet (HFD) decreases lipolysis and increases the survival
      rate in the mice infected with T. cruzi during acute infection. However, the
      effect of HFD on oxidative stress in adipose tissue has not been examined in
      detail. In the present study we evaluated the effect of HFD on oxidative stress
      markers in both white and brown adipose tissues (WAT and BAT) during acute
      infection. We used qPCR to examine the mRNA expression levels of genes involved
      in several antioxidant defence systems, such as those acting in ROS metabolism,
      peroxidases, and relevant oxygen transporter genes. The result of our study
      showed that HFD regulates the expression levels of oxidative stress genes in
      adipose tissues and that these effects are often different in WAT and BAT. For
      instance, while HFD down-regulated the levels of most antioxidant genes in both
      WAT and BAT, it differentially affected the expression pattern of genes involved
      in ROS metabolism (e.g. peroxidases) in WAT and BAT tissues of infected mice.
      Together with our previous studies, these findings show that infection and diet
      both regulate antioxidant enzymes and other oxidative stress defenses in mouse
      adipose tissues during acute T. cruzi infection.

PMID- 30221261
TI  - High-energy flexible quasi-solid-state lithium-ion capacitors enabled by a
      freestanding rGO-encapsulated Fe3O4 nanocube anode and a holey rGO film cathode.
AB  - Flexible energy storage devices have become critical components for next
      generation portable electronics. In the present work, a flexible quasi-solid
      state lithium-ion capacitor (LIC) is developed based on graphene-based bendable
      freestanding films in a gel polymer electrolyte. A graphene encapsulated Fe3O4
      nanocube hybrid film (rGO@Fe3O4) has been fabricated as the anode of LICs through
      a filtration assisted self-assembly and the subsequent thermal annealing process.
      In this hybrid architecture, flexible and ultrathin graphene shells uniformly
      enwrap the Fe3O4 within the whole film, which can effectively suppress the
      aggregation of Fe3O4 and also accommodate the volume change of Fe3O4 during the
      cycling process. As a consequence, the electrochemical performance of the
      rGO@Fe3O4 half-cell versus Li/Li+ shows high specific capacity (731 mA h g-1 at
      0.1 A g-1), excellent rate capability (210 mA h g-1 at 10 A g-1) and superior
      cycling stability (98% retention after 600 cycles). After chemically etching
      rGO@Fe3O4 with hydrochloric acid, a holey rGO film is successfully obtained as a
      high-rate cathode of LICs. On the basis of such a flexible anode and cathode, the
      as-fabricated quasi-solid-state LIC device delivers a high energy density of 148
      W h kg-1, a high power density of 25 kW kg-1 (achieved at 70 W h kg-1) and an
      excellent capacity retention of 82% after 2000 cycles. More importantly, the
      rGO@Fe3O4//holey rGO LIC shows good mechanical flexibility with stable Li-storage
      capacities under harsh bending.

PMID- 30221260
TI  - A supervoxel based random forest synthesis framework for bidirectional MR/CT
      synthesis.
AB  - Synthesizing magnetic resonance (MR) and computed tomography (CT) images (from
      each other) has important implications for clinical neuroimaging. The MR to CT
      direction is critical for MRI-based radiotherapy planning and dose computation,
      whereas the CT to MR direction can provide an economic alternative to real MRI
      for image processing tasks. Additionally, synthesis in both directions can
      enhance MR/CT multi-modal image registration. Existing approaches have focused on
      synthesizing CT from MR. In this paper, we propose a multi-atlas based hybrid
      method to synthesize T1-weighted MR images from CT and CT images from T1-weighted
      MR images using a common framework. The task is carried out by: (a) computing a
      label field based on supervoxels for the subject image using joint label fusion;
      (b) correcting this result using a random forest classifier (RF-C); (c) spatial
      smoothing using a Markov random field; (d) synthesizing intensities using a set
      of RF regressors, one trained for each label. The algorithm is evaluated using a
      set of six registered CT and MR image pairs of the whole head.

PMID- 30221262
TI  - Singlet fission in self-assembled PDI nanocrystals.
AB  - Upon photoexcitation, self-assembled PDI nanocrystals (S1S0) in the form of rods
      of 70 nm width and 1 MUm length are subject to a symmetry breaking charge
      separation (SBCS) as the first step in the singlet fission (SF) sequence. Hereby,
      the correlated pair of triplet excited states 1(T1T1) is formed with a quantum
      yield of 122%. Decoherence and triplet diffusion within the nanocrystals affords
      a long-lived, uncorrelated pair of triplet excited states (T1 + T1) with a
      quantum yield of 24%.

PMID- 30221263
TI  - Fluorescent and photoacoustic bifunctional probe for the detection of ascorbic
      acid in biological fluids, living cells and in vivo.
AB  - Photoacoustic imaging (PAI) has emerged as a promising clinical technology,
      thanks to its high-resolution in deep tissues. However, the lack of specificity
      towards analytes limits further application of the PA probe in molecular imaging.
      To this end, we herein report a PA and fluorescence (FL) dual-modal probe for the
      selective detection of ascorbic acid (AA). To realize this design, cobalt
      oxyhydroxide (CoOOH) was adopted as a multifunctional platform (PA contrast
      agent, FL quencher and specific oxidant to AA) and hybridized with red-emissive
      carbon dots (RCDs). In the presence of AA, CoOOH is reduced to Co2+ and meanwhile
      releases RCDs, resulting in the decrease of PA and recovery of FL signals. We
      demonstrated the AA detection capabilities of the probe in complicated biological
      fluids (human serum and urine), living cells, and dual-modal FL/PA imaging in
      vivo. This work revealed the PAI capacity of CoOOH for the first time, which may
      inspire researchers to design other CoOOH-based PA probes and further employ RCDs
      in biology and the clinic.

PMID- 30221264
TI  - Synthesis of a (N,C,C) Au(iii) pincer complex via Csp3-H bond activation:
      increasing catalyst robustness by rational catalyst design.
AB  - A (N,CAr,CAlk) Au(iii) pincer complex has been synthesized from Au(OAc)3 (OAc =
      OCOCH3) and 2-(3,5-di-tert-butylphenyl)pyridine (L1) involving a Csp3-H bond
      activation by electrophilic substitution. In agreement with DFT calculations, the
      resulting complex significantly improves the performance of Au(tpy)(OAcF)2 (tpy =
      2-(p-tolyl)pyridine, OAcF = OCOCF3) in the catalytic trifluoroacetylation of
      acetylene.

PMID- 30221265
TI  - Nitrogen substitution improves the mobility and stability of electron transport
      materials for inverted perovskite solar cells.
AB  - A suitable electron transport material (ETM) plays key roles in efficient
      perovskite solar cells (PSCs), because it is beneficial for exciton dissociation
      and charge transport at the interface thus increasing the short circuit current
      density. Based on the experimentally reported efficient electron transport
      molecule 10,14-bis(5-(2-ethylhexyl)thiophen-2-yl)-dipyrido[3,2-a:2',3'
      c][1,2,5]thiadiazolo[3,4-i]phenazine (TDTP), we theoretically design a set of new
      ETMs (TDTP-1, TDTP-2a, TDTP-2b, TDTP-3a, and TDTP-3b) by introducing a nitrogen
      atom into the thiophene ring or replacing a hydrogen atom on the methyl with an
      amino group. Quantum-chemical calculations reveal that the designed molecules
      behave much better than TDTP in terms of electron mobility, air stability, and
      solubility, where the electron mobility of TDTP-3b is two orders of magnitude
      higher than that of TDTP owing to the extra SN interactions in TDTP-3b that lead
      to the quasi two-dimensional pi packing motif which facilitates electron
      transport evidently. Moreover, we find that the substitution effect of the
      nitrogen atom strongly depends on the position, where the nitrogen atom at the
      beta-position of the thiophene ring (TDTP-2b and TDTP-3b) is more conducive to
      electron transport. Importantly, our calculations show that the ETM/perovskite
      interface interaction is enhanced after the introduction of the nitrogen atom and
      amino group thanks to the added NPb interaction, which favors electron transport
      with the newly designed ETMs. Our results not only report a set of novel
      promising ETMs, but also provide a useful design strategy for efficient ETMs.

PMID- 30221266
TI  - Cadmium exposure during pregnancy and lactation: materno-fetal and newborn
      repercussions of Cd(ii), and Cd-metallothionein complexes.
AB  - Cadmium (Cd) is a non-physiological heavy metal that can be harmful at low
      concentrations. Increasing anthropogenic activities are incrementing the risk of
      accumulation of this heavy metal in different organs and tissues of the body. In
      the case of pregnant women, the threat is more serious due to the implications
      affecting not only their own health but also fetal development as well.
      Metallothioneins (MTs), small cysteine-rich proteins, are involved in zinc (Zn)
      and copper homeostasis in mammals but can, however, also bind with Cd if present.
      The accumulation of Cd in maternal tissues (e.g. placenta, maternal blood, and
      mammary glands) induces the synthesis of MTs, preferably MT2, in an attempt to
      sequester the metal to avoid toxicity. The formed Cd-MT complexes will avoid the
      Cd transport from the placenta to the fetus and end up accumulating in the
      maternal kidneys. At the same time, high concentrations of MTs will increase the
      formation of Zn-MT complexes, therefore decreasing the amount of Zn ions
      available to be transported to the fetus by means of Zn transporters such as
      ZnT2, ZIP14 and DMT1. Although MTs cannot transport Cd from the mother to the
      fetus, the divalent DMT1 transporter is suggested to carry the metal to the
      fetus. As a consequence, the low levels of Zn(ii) in the fetus, together with the
      presence of Cd(ii) coming from the mother either via the placenta and cord blood
      or via breast milk induce changes in the fetal development including fetal growth
      retardation, and low weight or height of the newborn. Likewise, the
      concentrations of Cd(ii) in the newborn can cause alterations such as cognitive
      disabilities. In summary, the presence of Cd(ii) in the maternal tissues will
      induce MT synthesis in an attempt to detoxify these tissues and reduce the
      possible toxicity of Cd in fetal and newborn tissues.

PMID- 30221267
TI  - Functional biodegradable polymers via ring-opening polymerization of monomers
      without protective groups.
AB  - Biodegradable polymers are of current interest and chemical functionality in such
      materials is often demanded in advanced biomedical applications. Functional
      groups often are not tolerated in the polymerization process of ring-opening
      polymerization (ROP) and therefore protective groups need to be applied.
      Advantageously, several orthogonally reactive functions are available, which do
      not demand protection during ROP. We give an insight into available, orthogonally
      reactive cyclic monomers and the corresponding functional synthetic and
      biodegradable polymers, obtained from ROP. Functionalities in the monomer are
      reviewed, which are tolerated by ROP without further protection and allow further
      post-modification of the corresponding chemically functional polymers after
      polymerization. Synthetic concepts to these monomers are summarized in detail,
      preferably using precursor molecules. Post-modification strategies for the
      reported functionalities are presented and selected applications highlighted.

PMID- 30221268
TI  - A novel sPEEK nanocomposite membrane with well-controlled sPOSS aggregation in
      tunable nanochannels for fast proton conduction.
AB  - To greatly increase the proton conductivity of a sPEEK nanocomposite membrane
      without water swelling problems, sulfonated PEEK (sPEEK) nanocomposite membranes
      were prepared by regulating the nanocomposite concentration of sulfonated POSS
      (sPOSS). Incorporation of sPOSS into sPEEK afforded a 39% increase in proton
      conductivity at 80  degrees C/100% RH and a 70% increase in cell performance at
      1.5 wt% sPOSS concentration. In particular, water swelling problems were not
      observed even with the attained proton conductivity, as with Nafion. The water
      swelling of the pristine sPEEK membrane was 18.8%; it increased to 24.4% at 5.0
      wt% of sPOSS loading, which was 11.1% lower than that of Nafion. The high modulus
      of sPOSS and the good distribution of sPOSS also enhanced the tensile strength by
      40.5% and the strain by 65.8% compared with the pristine sPEEK membrane. At more
      than 1.5 wt% sPOSS concentration, the conductivity and power output of the
      nanocomposite membranes decreased despite the increased IEC, which is highly
      related to aggregation of sPOSS nanoparticles in the proton conducting
      nanochannels and changes in the nanochannel size. The sizes of the nanochannels
      were measured by SAXS, and it was found that expansion of the nanochannels was
      enhanced at 1.5 wt% by the best distribution of sPOSS and absorption of water.
      The increased IEC, expanded nanochannels and distribution of sPOSS without
      aggregation promoted proton conduction through the nanochannels.

PMID- 30221269
TI  - Nanodots of transition metal (Mo and W) disulfides grown on NiNi Prussian blue
      analogue nanoplates for efficient hydrogen production.
AB  - Lowering the dimension of transition metal dichalcogenides is an efficient
      approach to expose more S-edge-sites. Here, zero-dimensional MoS2 and WS2
      nanodots are successfully prepared with the assistance of a template of NiNi
      Prussian blue analogue nanoplates. The novel hybrids exhibit highly efficient and
      stable catalytic ability for the hydrogen evolution reaction.

PMID- 30221270
TI  - Preparation of long linear carbon chain inside multi-walled carbon nanotubes by
      cooling enhanced hydrogen arc discharge method.
AB  - Long linear carbon chains with sp hybridization inside multi-walled carbon
      nanotubes (LLCC@MWCNTs) can be prepared in the cathode deposits obtained by
      hydrogen arc discharge. In this work, a cooling system was introduced into the
      hydrogen arc discharge method to improve the growth yield of LLCC@MWCNTs samples,
      as indicated by the corresponding stronger Raman peaks between 1780 cm-1 and 1880
      cm-1, compared with conventional systems. Moreover, the cooling largely expanded
      the narrow scope of suitable conditions for the preparation of LLCC@MWCNTs, and
      high purity samples were easily produced. Qualitative analysis of arc discharge
      process helped conclude that cooling helps to increase the temperature of arc
      plasma, which is beneficial to improve both the growth yield of LLCC@MWCNTs and
      the purity of MWCNTs. This work provides a new approach to improve the growth
      yield of LLCC@MWCNTs and will benefit further studies and future applications of
      this new one-dimensional allotrope.

PMID- 30221271
TI  - Palladium nanoparticle formation processes in fluoropolymers by thermal
      decomposition of organometallic precursors.
AB  - Palladium nanoparticles were synthesized directly in solid fluoropolymer films by
      thermal decomposition of a palladium acetylacetonate precursor molecularly
      infused in the fluoropolymer matrix. This chemical infusion synthesis technique
      was studied using transmission electron microscopy along with selective area
      electron diffraction to gain insight into the nucleation and growth of palladium
      nanoparticles. Formation of palladium nanoparticles can be correlated with
      defects in the polymer matrix as well as their associated free volume such that a
      relationship between average particle size and mean free volume fraction can be
      constructed. At low processing temperatures, the average particle radius
      increases monotonically with the processing time but more complicated variations
      occur for longer times. The growth of nanoparticles was interpreted using a
      modified diffusion-limited growth model. While nearly monodisperse nanoparticles
      dispersed throughout the polymer volume were obtained at low processing
      temperatures, surface percolation of nanoparticles was observed at relatively
      high temperatures owing to high precursor decomposition and diffusion rates.

PMID- 30221272
TI  - On the formation and the isomer specific detection of methylacetylene (CH3CCH),
      propene (CH3CHCH2), cyclopropane (c-C3H6), vinylacetylene (CH2CHCCH), and 1,3
      butadiene (CH2CHCHCH2) from interstellar methane ice analogues.
AB  - Pure methane (CH4) ices processed by energetic electrons under ultra-high vacuum
      conditions to simulate secondary electrons formed via galactic cosmic rays (GCRs)
      penetrating interstellar ice mantles have been shown to produce an array of
      complex hydrocarbons with the general formulae: CnH2n+2 (n = 4-8), CnH2n (n = 3
      9), CnH2n-2 (n = 3-9), CnH2n-4 (n = 4-9), and CnH2n-6 (n = 6-7). By monitoring
      the in situ chemical evolution of the ice combined with temperature programmed
      desorption (TPD) studies and tunable single photon ionization coupled to a
      reflectron time-of-flight mass spectrometer, specific isomers of C3H4, C3H6,
      C4H4, and C4H6 were probed. These experiments confirmed the synthesis of
      methylacetylene (CH3CCH), propene (CH3CHCH2), cyclopropane (c-C3H6),
      vinylacetylene (CH2CHCCH), 1-butyne (HCCC2H5), 2-butyne (CH3CCCH3), 1,2-butadiene
      (H2CCCH(CH3)), and 1,3-butadiene (CH2CHCHCH2) with yields of 2.17 +/- 0.95 * 10
      4, 3.7 +/- 1.5 * 10-3, 1.23 +/- 0.77 * 10-4, 1.28 +/- 0.65 * 10-4, 4.01 +/- 1.98
      * 10-5, 1.97 +/- 0.98 * 10-4, 1.90 +/- 0.84 * 10-5, and 1.41 +/- 0.72 * 10-4
      molecules eV-1, respectively. Mechanistic studies exploring the formation routes
      of methylacetylene, propene, and vinylacetylene were also conducted, and revealed
      the additional formation of the 1,2,3-butatriene isomer. Several of the above
      isomers, methylacetylene, propene, vinylacetylene, and 1,3-butadiene, have
      repeatedly been shown to be important precursors in the formation of polycyclic
      aromatic hydrocarbons (PAHs), but until now their interstellar synthesis has
      remained elusive.

PMID- 30221273
TI  - Effect of liquid droplet surface tension on impact dynamics over hierarchical
      nanostructure surfaces.
AB  - Analyzing impact dynamics is important for practical applications of
      superhydrophobic surfaces, because these nonwetting surfaces frequently encounter
      impacting liquid droplets in real environments. Thus, various studies have been
      conducted to investigate impact dynamics by examining the correlation between the
      behaviors of impacting liquid droplets and several determining parameters, such
      as impacting velocity, surface structure and surface energy. The impacting
      behaviors of pure water droplets were the main focus in most previous studies;
      the effect of surface tension, another critical parameter, on impact dynamics has
      rarely been investigated. In the current work, we have newly studied the effects
      of liquid surface tension on impact dynamics using an ethanol-water solution as a
      model liquid system. We systematically varied the liquid's surface tension
      between 72 and 32 mN m-1 by changing the ethanol concentration from 0 to 20 wt%.
      This range of composition drastically changed the surface tension while it did
      not significantly affect other physical properties, such as density and
      viscosity. For an impact dynamics study, two surfaces, namely ZnO nanowires (NWs)
      and ZnO/Si hierarchical (HIE) structures, were prepared. As the surface tension
      decreased, the static water contact angle (CA) decreased on both surfaces. Under
      dynamic conditions, our analysis using a high-speed camera and a quartz crystal
      microbalance (QCM) showed that lowering the surface tension causes the transition
      from the anti-wetting to wetting state. The transition We numbers were obtained
      on both surfaces for various surface tensions of liquids. Under the same dropping
      conditions of liquids, the ZnO/Si HIE surface shows higher transition We numbers
      than the ZnO NW surface, which is due to the higher fraction of air pockets in
      the hierarchical structure, originating from dual dimensional structures. To
      understand the mechanism of dynamic transition, we developed a model for ZnO/Si
      HIE structures based on three determining pressures: anti-wetting, wetting, and
      effective water hammer pressures. The modeling results explain the experimental
      observations. The results of our model system are highly useful for understanding
      the impact dynamic behaviors of various liquids on non-wetting surfaces.

PMID- 30221274
TI  - Oxidative coupling strategies for the synthesis of indole alkaloids.
AB  - Direct bond formation between two C-H bonds is most challenging but imperative
      for efficient organic synthesis. Recently, significant progress has been made in
      direct functionalization of indole through oxidative coupling reactions with
      other nucleophiles such as enolates and phenols. Both intermolecular and
      intramolecular coupling reactions can be conducted under the action of
      base/oxidants or oxidants alone. Coupling typically occurs at the 3-position of
      indole moiety due to intrinsic nucleophilicity at this position. Coupling at the
      2- or 4-position of the indole moiety has been observed for some special
      substrates. These coupling reactions provide powerful tools for quickly
      establishing the core structures of a number of indole alkaloids.

PMID- 30221275
TI  - Nano-flocks of a bimetallic organic framework for efficient hydrogen evolution
      electrocatalysis.
AB  - Nano-flocks of a bimetallic organic framework (NiCo-MOF) were grown on a nickel
      mesh and covered with a graphene oxide aerosol skeleton by employing a nebulizer
      air compressor. The resulting material induces a high accessible active surface
      area and shows enhanced electrocatalytic activity towards the hydrogen evolution
      reaction with excellent stability in alkaline medium.

PMID- 30221276
TI  - Morphology of soft and rough contact via fluid drainage.
AB  - The dynamic of contact formation between soft materials immersed in a fluid is
      accompanied by fluid drainage and elastic deformation. As a result, controlling
      the coupling between lubrication pressure and elasticity provides strategies to
      design materials with reversible and dynamic adhesion to wet or flooded surfaces.
      We characterize the elastic deformation of a soft coating with nanometer-scale
      roughness as it approaches and contacts a rigid surface in a fluid environment.
      The lubrication pressure during the approach causes elastic deformation and
      prevents contact formation. We observe deformation profiles that are drastically
      different from those observed for elastic half-space when the thickness of the
      soft coating is comparable to the hydrodynamic radius. In contrast, we show that
      surface roughness favors fluid drainage without altering the elastic deformation.
      As a result, the coupling between elasticity and slip (caused by surface
      roughness) can lead to trapped fluid pockets in the contact region.

PMID- 30221277
TI  - Resonance energy transfer and electron-hole annihilation induced
      chemiluminescence of quantum dots for amplified immunoassay.
AB  - The chemiluminescence (CL) of CdTe quantum dots (QDs) in the presence of
      peroxyoxalate and hydrogen peroxide was explored and applied for sensitive
      immunoassay, in which the amplified CL originated from the resonance energy
      transfer and annihilation of hole-injected and electron-injected QDs.

PMID- 30221278
TI  - Exploring physicochemical space via a bioisostere of the trifluoromethyl and
      ethyl groups (BITE): attenuating lipophilicity in fluorinated analogues of
      Gilenya(r) for multiple sclerosis.
AB  - The direct, catalytic vicinal difluorination of terminal alkenes via an
      I(i)/I(iii) manifold was exploited to install a chiral, hybrid bioisostere of the
      CF3 and Et groups (BITE) in Gilenya(r); the first orally available drug for the
      clinical management of Multiple Sclerosis (MS). This subtle fluorination pattern
      allows lipophilicity (log D) to be tempered compared to the corresponding CF3 and
      Et derivatives (CH2CH3 > CH2CF3 > CHFCH2F).

PMID- 30221279
TI  - Xylopsides A-D, four rare guaiane dimers with two unique bridged pentacyclic
      skeletons from Xylopia vielana.
AB  - Four unprecedented guaiane dimers, xylopsides A-D (1-4), were isolated and
      identified from the roots of Xylopia vielana. The structures of 1-4 were
      elucidated by spectroscopic analysis, Cu Kalpha X-ray crystallography and CD
      spectra. 1-4 showed two bridged pentacyclic skeletons between two guaiane-type
      sesquiterpenes, which were characterized as two different bridged ring systems.
      Among these compounds, 4 exhibited a moderate inhibitory activity against the
      production of nitric oxide with an IC50 value of 25.7 MUM in RAW264.7 cells
      stimulated by LPS.

PMID- 30221280
TI  - Ultraviolet lasing in Zn-rich ZnO microspheres fabricated by laser ablation.
AB  - Zinc (Zn) surface plasmons (SPs) have been widely reported for their impressive
      performance in improving the optical properties of semiconductors. Zn is an
      effective metal with SPs response in the ultraviolet region, but the disadvantage
      of strong metal activity limits the application mentioned above. Here, in order
      to ensure the stability of metal Zn, ZnO/Zn microspheres were synthesized by an
      one-step laser ablation method to distribute Zn nanoparticles simultaneously on
      both inner and outer surfaces of ZnO microspheres. Lasing performance enhancement
      and a lower threshold were obtained in the composite which originates from the
      coupling between Zn SPs and the excitation light source. Accompanied by the
      lasing emission measurements, the coupling mechanism was explained through time
      resolved photoluminescence spectroscopy (TRPL) for the samples by rapid annealing
      in situ. This work displays the results of lasing enhancement and the physical
      process of Zn SPs resonance in the ZnO/Zn microsphere.

PMID- 30221281
TI  - In situ formed nanoparticle-assisted growth of large-size single crystalline h-BN
      on copper.
AB  - h-BN is a widely used ultrathin insulator that can be synthesized in a
      controllable manner by chemical vapor deposition, similar to the growth of
      graphene. However, it is challenging to grow large-size single crystalline h-BN
      because of the ambiguous understanding of its growth mechanism. In this study, we
      propose a novel in situ formed nanoparticle-assisted growth strategy for large
      size single crystalline h-BN growth on conventional polycrystalline copper. We
      found that the areal nucleation density of h-BN can be suppressed from ~105
      nuclei per mm2 to ~102 nuclei per mm2 by the in situ formed nanoparticles that
      were introduced by pre-oxidation. Thus, single crystalline h-BN with lateral
      length of up to ~102 MUm was readily synthesized. Furthermore, for first time we
      discovered that the areal nucleation density of h-BN initially decreases and then
      increases under extreme annealing conditions, indicating that there is a
      competition-induced limit for suppressing the nucleation of h-BN on copper. This
      mechanism is universal for h-BN and graphene synthesis, which probably paves the
      way for large-size graphene/h-BN heterostructures synthesis in the future.

PMID- 30221282
TI  - Electronic structure of the para-dinitrobenzene radical anion: a combined 2D
      photoelectron imaging and computational study.
AB  - The para-dinitrobenzene radical anion has been studied by 2D photoelectron
      imaging within the energy range of 2.5 eV above the detachment threshold.
      Supporting electronic structure calculations at the XMCQDPT2 level of the excited
      states and resonances are presented. The direct photodetachment channel has been
      observed and modelled, and yields an electron affinity of 1.99 +/- 0.01 eV. In
      addition to the direct channel, evidence of resonances is observed. These
      resonances, which are symmetry allowed for photoexcitation from the ground state
      and of Feshbach types with respect to the open continuum, result in fast internal
      conversion to bound electronic states, followed by statistical electron emission
      observed at very low kinetic energies as well as dissociation of the nitrite
      anion. The latter is seen in the photoelectron spectra, which can be modelled as
      a combination of direct detachment from the para-dinitrobenzene and nitrite
      anions. An additional dimension has been offered by the 2D photoelectron angular
      distribution that is particularly sensitive to a mechanism of electron
      detachment, allowing us to confidently interpret the production of the nitrite
      anion photofragment.

PMID- 30221283
TI  - Lewis acid-catalyzed Friedel-Crafts reactions toward highly versatile, alpha
      quaternary oxime ethers.
AB  - The synthesis of all-carbon-substituted, quaternary stereocenters through Lewis
      acid-catalyzed Friedel-Crafts alkylation of cyclic and acyclic 2-hydroxy oxime
      ethers proceeds under mild reaction conditions and with high yields. Moreover,
      the oxime ether moiety can be easily manipulated into various functional groups
      through subsequent modifications.

PMID- 30221284
TI  - Anoxic photocatalytic treatment of synthetic mining wastewater using TiO2 and
      scavengers for complexed cyanide recovery.
AB  - The wastewater from gold exploitation is well known for the toxic nature of
      recalcitrant cyanide metallic complexes. In this work the selectivity in the
      photocatalytic degradation of gold mining wastewater (Fe(CN)63-) using suspended
      TiO2 with alcoholic and organic acid scavengers in a mini-CPC photoreactor with a
      30 W UV-A LED as an artificial source of light was evaluated. The study was done
      in four stages: 1. load catalyst determination, 2. combination of scavengers in a
      typical photocatalytic degradation, 3. evaluation of scavenger concentration and
      4. kinetic study. The decomposition into CN- and Fe removal of the cyanocomplex
      were tracked. It was observed that formic acid (FA) and t-butanol (t-ButOH) were
      the best scavengers for the photocatalytic degradation under anoxic conditions.
      The best concentrations of acceptors used in the study were 10 mM FA and 10 mM t
      ButOH at 20 W m-2 of UV-A power, reaching 80% degradation of Fe(CN)63-, 40% Fe
      removal and 18 ppm of free cyanide CN release to the liquid phase. The electrical
      efficiency of oxidation per order (EEo) was increased by about 50% with the
      addition of scavengers instead of traditional anoxic photocatalytic treatment. It
      was proved that the photocatalytic decomposition of the Fe cyanocomplex was done
      through the photoreduction path of the metal complex.

PMID- 30221285
TI  - Sensing the chirality of various organic solvents by helically arranged pi
      blades.
AB  - Although the chiral enrichment of dynamic prochiral molecules usually requires a
      strong interaction with a chiral source, the enantiomer ratio of a propeller
      shaped molecule, obtained by a recently developed boron-mediated benzannulation
      reaction of alkynes, is biased in various organic solvents through solvation for
      the propeller moieties.

PMID- 30221286
TI  - Simultaneous activity and surface area measurements on single mesoporous
      nanoparticle aggregates.
AB  - The underpotential deposition of hydrogen and the hydrogen evolution reaction is
      studied at individual mesoporous nanoparticles. This work shows how the
      electroactive surface area and catalytic activity of these individual particles
      can be simultaneously measured.

PMID- 30221287
TI  - Correction: Facile synthesis of silver nanowire-zeolitic imidazolate framework 67
      composites as high-performance bifunctional oxygen catalysts.
AB  - Correction for 'Facile synthesis of silver nanowire-zeolitic imidazolate
      framework 67 composites as high-performance bifunctional oxygen catalysts' by
      Yuyin Wang et al., Nanoscale, 2018, 10, 15755-15762.

PMID- 30221288
TI  - Multi-lumen capillary based trypsin micro-reactor for the rapid digestion of
      proteins.
AB  - In this work we evaluated a novel microreactor prepared using a surface modified,
      high surface-to-volume ratio multi-lumen fused silica capillary (MLC). The MLC
      investigated contained 126 parallel channels, each of 4 MUm internal diameter.
      The MLC, along with conventional fused silica capillaries of 25 MUm and 50 MUm
      internal diameter, were treated by (3-aminopropyl)triethoxysilane (APTES) and
      then modified with gold nanoparticles, of ~20 nm in diameter, to ultimately
      provide immobilisation sites for the proteolytic enzyme, trypsin. The modified
      capillaries and MLCs were characterised and profiled using non-invasive scanning
      capacitively coupled contactless conductivity detection (sC4D). The sC4D profiles
      confirmed a significantly higher amount of enzyme was immobilised to the MLC when
      compared to the fused silica capillaries, attributable to the increased surface
      to volume ratio. The MLC was used for dynamic protein digestion, where peptide
      fragments were collected and subjected to off-line chromatographic evaluation.
      The digestion was achieved with the MLC reactor, using a residence time of just
      1.26 min, following which the HPLC peak associated with the intact protein
      decreased by >70%. The MLC reactors behaved similarly to the classical in vitro
      or in-solution approach, but provided a reduction in digestion time, and fewer
      peaks associated with trypsin auto-digestion, which is common using in-solution
      digestion. The digestion of cytochrome C using both the MLC-IMER and the in
      solution approach, resulted in a sequence coverage of ~80%. The preparation of
      the MLC microreactor was reproducible with <2.5% RSD between reactors (n = 3) as
      determined by sC4D.

PMID- 30221289
TI  - Development of a novel FePt-based multifunctional ferroptosis agent for high
      efficiency anticancer therapy.
AB  - Ferroptosis as an emerging mechanism has become a research hotspot for killing
      cancer cells. In this work, a novel ferroptosis agent, FePt-PTTA-Eu3+-FA (FPEF),
      was rationally designed by harnessing the luminescent lanthanide complexes PTTA
      Eu3+ and folic acid (FA) in FePt nanoparticles. FePt-Based nanomaterials have
      potential applications in magnetic resonance imaging/computed tomography (MRI/CT)
      in clinical diagnosis and have excellent capacity to induce cancer cell death.
      Mechanistic studies of FPEP showed that the FePt induced cancer cell death was
      affirmed as the ferroptosis mechanism. To the best of our knowledge, it will be
      the first report that proves the existence of the ferroptosis process in FePt
      NPs. The in vitro tests of FPEF demonstrated that the as-prepared NPs exhibit a
      satisfactory anticancer effect towards FA-positive tumor cells including 4T1, MCF
      7 and HeLa cells. The in vivo studies using tumor-bearing balb/c mice revealed
      that the FPEF NPs could significantly inhibit tumor progression. Such all-in-one
      therapeutic strategies have great potential in early diagnosis, prognosis and
      treatment of cancer.

PMID- 30221290
TI  - On the influence of multiple cations on the in-gap states and phototransport
      properties of iodide-based halide perovskites.
AB  - In-gap states in solar cell absorbers that are recombination centers determine
      the cell's photovoltaic performance. Using scanning tunneling spectroscopy (STS),
      temperature-dependent photoconductivity and steady-state photocarrier-grating
      measurements we probed, directly and indirectly, the energies of such states,
      both at the surface and in the bulk of two similar, but different halide
      perovskites, the single cation MAPbI3 (here MAPI) and the mixed cation halide
      perovskite, FA0.79MA0.16Cs0.05Pb(I0.83Br0.17)3 (here MCHP). We found a
      correlation between the energy distribution of the in-gap states, as determined
      by STS measurements, and their manifestation in the photo-transport parameters of
      the MCHP absorbers. In particular, our results suggest that the in-gap
      recombination centers in the MCHP are shallower than those of MAPI. This can be
      one explanation for the better photovoltaic efficiency of the former.

PMID- 30221291
TI  - Effective lead optimization targeting the displacement of bridging receptor
      ligand water molecules.
AB  - Enhancing the binding affinities of ligands by means of lead modifications that
      displace bridging water molecules at protein-ligand interfaces is an important
      and widely studied lead optimization strategy. However, it is still challenging
      to ensure the success of this lead optimization strategy. Here we use theoretical
      derivations, which are then validated using reported experimental data, to
      identify the major determining factors in lead optimization designed to displace
      bridging water molecules. Our findings demonstrate that the nature of hydrogen
      bond pairing between the ligand and protein polar atom(s) is the principal factor
      displacing interface water molecules, and not the binding strength of the water
      molecule. Our results also indicate that all interfacing bridging water molecules
      can potentially be targeted for displacement using this new approach. In summary,
      we show that strong-strong/weak-weak hydrogen-bond pairings of ligand atoms with
      protein atoms may provide useful guidance in lead modifications by designing
      modified ligands with higher binding affinities than their lead molecules. This
      study can help to increase the efficiency of rational drug design.

PMID- 30221292
TI  - Measurement of the surface hydrophobicity of engineered nanoparticles using an
      atomic force microscope.
AB  - Determination of the surface hydrophobicity or wettability of nanomaterials and
      nanoparticles (NPs) is often challenged by the heterogeneous properties of NPs
      that vary with particle size, shape, surface charge, aggregation states, and
      surface sorption or coating. This study first summarized inherent limitations of
      the water contact angle, octanol-water partition coefficient (Kow) and surface
      adsorption of probe molecules in probing nanomaterial hydrophobicity. Then, we
      demonstrated the principle of a scanning probe method based on atomic force
      microscopy (AFM) for the local surface hydrophobicity measurement. Specifically,
      we measured the adhesion forces between functionalized AFM tips and self
      assembled monolayers (SAMs) to establish a linear relationship between the
      adhesion forces and water contact angles based on the continuum thermodynamic
      approach (CTA). This relationship was used to determine the local surface
      hydrophobicity of seven different NPs (i.e., TiO2, ZnO, SiO2, CuO, CeO2, alpha
      Fe2O3, and Ag), which agreed well with bulk contact angles of these NPs. Some
      discrepancies were observed for Fe2O3, CeO2 and SiO2 NPs, probably because of
      surface hydration and roughness effects. Moreover, the solution pH and ionic
      strength had negligible effects on the adhesion forces between the AFM tip and
      MWCNTs or C60, indicating that the hydrophobicity of carbonaceous nanomaterials
      is not influenced by pH or ionic strength (IS). By contrast, natural organic
      matter (NOM) appreciably decreased the hydrophobicity of MWCNTs and C60 due to
      surface coating of hydrophilic NOM. This scanning probe method has been proved to
      be reliable and robust toward the accurate measurement of the nanoscale
      hydrophobicity of individual NPs or nanomaterials in liquid environments.

PMID- 30221293
TI  - The dimensional and hydrogenating effect on the electronic properties of ZnSe
      nanomaterials: a computational investigation.
AB  - We performed a comprehensive first-principles study on the structural and
      electronic properties of ZnSe two-dimensional (2D) nanosheets and their derived
      one-dimensional (1D) nanoribbons (NRs) and nanotubes (NTs). Both hexagonal and
      tetragonal phases of ZnSe (h-ZnSe and t-ZnSe) were considered. The tetragonal
      phase is thermodynamically more favorable for 2D monolayers and 1D pristine
      ribbons, in contrast, the hexagonal phase is preferred for the edge-hydrogenated
      1D NRs and NTs. The 2D h-ZnSe monolayer is a direct-bandgap semiconductor. Both
      the pristine zigzag nanoribbons (z-hNRs) and the corresponding edge-hydrogenated
      NRs gradually convert from the direct-bandgap semiconducting phase into a
      metallic phase as the ribbon width increases; the pristine armchair nanoribbons
      (a-hNRs) remain as semiconductors with indirect bandgaps with increasing ribbon
      width, and edge hydrogenating switches the indirect-bandgap feature to the direct
      bandgap character or the metallic character with different edge passivation
      styles. The 1D h-ZnSe single-walled nanotubes in both armchair and zigzag forms
      keep the direct-bandgap semiconducting property of the 2D counterpart but with
      smaller band gaps. For the thermodynamically more favorable t-ZnSe monolayer, the
      intrinsic direct-bandgap semiconducting character is rather robust: the derived
      1D nanoribbons with edges unsaturated or hydrogenated fully, and 1D single-walled
      nanotubes all preserve the direct-bandgap semiconducting feature. Our systemic
      study provides deep insights into the electronic properties of ZnSe-based
      nanomaterials and is helpful for experimentalists to design and fabricate ZnSe
      based nanoelectronics.

PMID- 30221294
TI  - Reaction kinetics and a physical model of the charring layer by depositing Al2O3
      at ultra-high temperatures.
AB  - The thermochemical ablation of insulation material caused by slag deposition in
      solid rocket motors has increasingly attracted researchers' attention.
      Understanding the ablation mechanism and the ability to calculate reaction
      kinetics parameters determine the height of the thermal protection design for
      advanced solid rocket motors. In this work, the interaction of the Al2O3-C system
      is determined through static ablation experiments. Using X-ray diffraction, HSC
      thermodynamic software, and a thermogravimetric analyser, the carbon thermal
      reduction of alumina is analysed and the reaction mechanism and physical model
      are obtained. Isothermal experiments at 1700-1850  degrees C and mathematical
      analysis provide the kinetic parameters of the overall and step-by-step
      reactions. The results show that the overall reaction of the Al2O3-C system
      involves three steps. The overall reaction kinetics are described by the
      contracting area model R2 with apparent activation and frequency factors
      estimated as 254.5 kJ mol-1 and 5.5 * 106 min-1, respectively. The distribution
      reaction kinetics of steps 1 and 2 are described by the first-order chemical
      reaction control model (F1) and that of step 3 is described by the one
      dimensional diffusion control model (D1). The corresponding activation energies
      are 107.9 kJ mol-1, 240.3 kJ mol-1, and 567.5 kJ mol-1, and frequency factors are
      625.94 min-1, 8.3 * 105 min-1, and 1.6 * 1014 min-1, respectively.

PMID- 30221295
TI  - Plasmonic targeting of cancer cells in a three-dimensional natural hydrogel.
AB  - Using specifically designed gold nanoparticles and local laser irradiation,
      individual cells and small cell clusters could be targeted on a microscopic scale
      with minimal toxicity to nearby tissue. To date, most scientific studies and
      technological demonstrations of this approach were conducted on two-dimensional
      cultures, while most feasibility tests and preclinical trials were conducted
      using animal models. For bridging the gap between two-dimensional cell cultures
      and animal experiments, we propose and demonstrate the use of a natural hydrogel
      for studying the effect of intense, ultrashort laser pulses on a gold
      nanoparticle targeted tissue. Using illumination parameters comparable to those
      used with two-dimensional cultures, we show the complete eradication of
      multilayered cell colonies comprising normal fibroblasts and malignant epithelial
      cells co-cultured on a hydrogel scaffold. By evaluating the extent of cell damage
      for various pulse durations at off-resonance irradiation, we find that the
      observed damage mechanism was dominated by rapid thermal transitions around the
      gold nanospheres, rather than by photoionization. The work provides a new tool
      for understanding the complex pulse-particle-tissue interactions and demonstrates
      the important role of nanoparticle mediated cavitation bubbles in a thick,
      multilayered tissue.

PMID- 30221296
TI  - Clustering and phase separation of circle swimmers dispersed in a monolayer.
AB  - We perform Brownian dynamics simulations in two dimensions to study the
      collective behavior of circle swimmers, which are driven by both, an (effective)
      translational and rotational self-propulsion, and interact via steric repulsion.
      We find that active rotation generally opposes motility-induced clustering and
      phase separation, as demonstrated by a narrowing of the coexistence region upon
      increase of the propulsion angular velocity. Moreover, although the particles are
      intrinsically assigned to rotate counterclockwise, a novel state of clockwise
      vortices emerges at an optimal value of the effective propulsion torque. We
      propose a simple gear-like model to capture the underlying mechanism of the
      clockwise vortices.

PMID- 30221297
TI  - Descriptors of magnetic anisotropy revisited.
AB  - The recently discovered thermal elasticity of magnetic anisotropy is not at all
      an exotic phenomenon. For many lanthanide complexes the qualitative nature of
      their magnetic anisotropy changes as a function of temperature and magnetic
      field; for some, even multiple times. The theoretically predicted existence of
      such multi-switch compounds is experimentally corroborated.

PMID- 30221298
TI  - Plasmonic chemically modified cotton nanocomposite fibers for efficient solar
      water desalination and wastewater treatment.
AB  - Water desalination and wastewater treatment via solar photothermal energy
      conversion are among the most important technologies to address the increasing
      pressing global water scarcity. Solar energy is the cleanest, most abundant,
      renewable natural resource available. Herein, we report the development of highly
      efficient, flexible, low weight, and cost effective Plasmonic Functionalized
      Cotton (PFC) nanocomposite materials for solar steam generation through the
      efficient evaporation of surface water pools. The PFC nanocomposites contain
      metallic nanoparticles that exhibit strong solar absorption followed by non
      radiative relaxation causing the absorbed energy to be converted into heat for
      efficient water evaporation. The chemically modified cotton leads to a partial
      hydrophobic surface that allows the material to float on the water's surface and
      provide excellent thermal insulation properties in addition to facile and
      scalable synthesis. The PFC nanocomposites containing Au and Ag nanoparticles are
      demonstrated to be among the most efficient solar thermal converters reported to
      date for solar water desalination. The Au/Ag-PFC fibers exhibit average water
      evaporation rates of 1.4 and 11.3 kg m-2 h-1 with superb solar thermal
      efficiencies of up to 86.3% and 94.3% under 1 and 8 sun illumination,
      respectively. Furthermore, the Au/Ag-PFC fibers display stable evaporation rates
      over more than 10 repeated evaporation cycles without any performance decline
      under acidic solution at pH 2 or basic solution at pH 10. The successful
      application of the Au/Ag-PFC fibers for the removal of organic dyes from
      contaminated water through the solar steam generation is also demonstrated. The
      high solar thermal evaporation efficiency, excellent stability and long-time
      durability make the PFC nanocomposites excellent candidates for applications in
      seawater desalination and wastewater treatment by solar-steam generation.

PMID- 30221299
TI  - Pre-melting and the adsorption of formic acid at the air-ice interface at 253 K
      as seen by NEXAFS and XPS.
AB  - Interactions between trace gases and ice are important in environmental chemistry
      and for Earth's climate. In particular, the adsorption of trace gases to ice
      surfaces at temperatures approaching the melting point has raised interest in the
      past, because of the prevailing pre-melting. Here, we present Near Edge X-ray
      Absorption Fine Structure (NEXAFS) spectroscopy data at ambient partial pressure
      of water to better define the onset temperature of pre-melting at the interfacial
      region of ice. Further, this study directly compares the interaction between an
      organic acid common in the atmosphere, formic acid, and that of an aliphatic
      carbon with ice at 253 K. It makes use of X-ray Photoelectron Spectroscopy (XPS)
      with its inherent narrow probing depth covering both the surface and near-surface
      bulk region when detecting electrons. We use the tender X-ray range for
      excitation to locate the organic species within the interfacial region with an
      extended probing depth compared to published XPS work. Electron kinetic energy
      dependent C1s photoemission data indicate that, at low coverage of a few 1014
      molecules cm-2, the presence of formic acid is restricted to the upper ice layers
      of the interfacial region. Increasing the dosage, formic acid penetrates 6-7 nm
      into the air-ice interface. The presence of the more hydrophobic aliphatic carbon
      is restricted to the upper ice monolayers. This direct comparison of an organic
      acid with an aliphatic compound confirms the emerging picture where solutes enter
      the interfacial region of ice at a depth related to their specific tendency to
      form solvation shells.

PMID- 30221300
TI  - Enhancement of lithium-ion hopping on halogen-doped chi3 borophene.
AB  - Borophenes, which are two-dimensional boron counterparts made of the three
      synthetic polymorphs T, beta12 and chi3, have been considered as potential anode
      materials in Li-ion batteries with extremely high capacities. However, Li hopping
      on beta12 and chi3 borophenes is quite slow with high energy barriers (around 0.6
      eV), thus preventing the application of these borophenes in the fast charging
      realm. Here, we have used halogen functionalization in an attempt to boost the
      sluggish Li-ion diffusion dynamics in the prototype chi3 borophene system.
      Halogens bind strongly to chi3 borophene with substantial electron transfer from
      the latter to the former, thereby leading to local electron deficiency in the
      chi3 borophene. The synergy of electron extraction from chi3 borophene and the
      electrostatic attraction between halogens and Li results in an enhanced affinity
      between chi3 borophene and Li as well as a reduction in the Li-ion hopping
      barrier. Iodine is the preferred dopant, for which most diffusion paths exhibit
      energy barriers typically smaller than 0.2 eV. Our results suggest that halogen
      incorporation could facilitate intercalation and de-intercalation of Li-ions in
      borophene-based anode materials.

PMID- 30221301
TI  - Photo/thermoresponsive ABC triblock copolymer-based ion gels: photoinduced
      structural transitions.
AB  - A photo/thermoresponsive ABC triblock copolymer-based ion gel exhibiting
      photoinduced structural transitions accompanied by significant rheological
      changes is newly developed. The ABC triblock copolymer comprises an ionic liquid
      (IL)-phobic A block, an IL-philic B block, and a photo/thermoresponsive C block
      containing azobenzene moieties. The IL-phobic A block forms a rigid micellar core
      in an IL over a wide temperature range and the photo/thermoresponsive C block
      undergoes upper critical solution temperature (UCST)-type phase transition in
      ILs. In concentrated polymer solution, the ABC triblock copolymer can form a
      percolated micellar network at low temperatures through aggregation of A and C
      blocks as physical crosslinks, bridged by IL-philic B blocks. In contrast, the
      ion gel undergoes structural transition to jammed micelles at high temperatures
      due to the disassembly of the thermoresponsive C block, resulting in significant
      softening of the ion gel. Importantly, the temperature dependences of the
      viscoelastic properties of the ion gel differ drastically depending on photo
      irradiation conditions as the photoinduced isomerization of azobenzene moieties
      in the C block modulates the affinity between the polymer chain and IL. Utilizing
      this feature, photoinduced softening/hardening of the ion gel is realized at
      constant temperature. This study provides a promising strategy to control the
      rheological properties of nonvolatile soft materials via contactless light
      irradiation that could be exploited in various applications such as
      photoresponsive soft actuators and photo-healable soft materials.

PMID- 30221302
TI  - Cadmium exposure in First Nations communities of the Northwest Territories,
      Canada: smoking is a greater contributor than consumption of cadmium-accumulating
      organ meats.
AB  - Traditional food consumption among northern populations is associated with
      improved nutrition but occasionally can also increase contaminant exposure. High
      levels of cadmium in the organs of moose from certain regions of the Northwest
      Territories, Canada, led to the release of consumption notices. These notices
      recommended that individuals limit their consumption of kidney and liver from
      moose harvested from the Southern Mackenzie Mountain. A human biomonitoring
      project was designed to better characterize exposure and risks from contaminants,
      including cadmium, among Dene/Metis communities of the Northwest Territories
      Mackenzie Valley, Canada. The project included a dietary assessment (food
      frequency questionnaire) to estimate moose and caribou organ (kidney and liver)
      consumption, as well as urine and blood sampling for the measurement of cadmium
      concentration using mass spectrometry. For a subset of the samples, urine
      cotinine was also quantified. The results from this biomonitoring research show
      that cadmium levels in urine (GM = 0.32 MUg L-1) and blood (GM = 0.58 MUg L-1)
      are similar to those observed in other populations in Canada. For the 38% of
      participants reporting eating game organs, current traditional food consumption
      patterns were not associated with cadmium biomarker levels. Instead, smoking
      appeared to be the main determinant of cadmium exposure. These results are
      supporting ongoing efforts at the community and territorial level to identify
      health priorities and design follow up plans in response to environmental
      monitoring data.

PMID- 30221303
TI  - A smart off-on copper sulfide photoacoustic imaging agent based on amorphous
      crystalline transition for cancer imaging.
AB  - By exploiting the amorphous-crystalline transition of CuS, which results in
      greatly increased absorption throughout the entire near-infrared region, a novel
      smart off-on CuS photoacoustic imaging agent with good photostability and low
      cost is developed. More importantly, the photoacoustic imaging ability of CuS can
      be effectively activated by body temperature for in vivo cancer imaging.

PMID- 30221304
TI  - First catalyst-free CO2 trapping of N-acyliminium ions under ambient conditions:
      sustainable multicomponent synthesis of thia- and oxazolidinyl carbamates.
AB  - The first trapping of N-acyliminium ions by in situ generated carbaminic acid
      (product of carbon dioxide (CO2) and amine) is reported. This catalyst-free
      reaction provides a convenient and feasible approach to prepare N-acyl thia- and
      oxazolidinyl carbamates with good functional-group compatibility and high
      efficiency under green conditions. Furthermore, the multicomponent method
      features a broad substrate scope, facile product diversification, smooth scale-up
      and notable potential for polymer applications.

PMID- 30221305
TI  - Effect of crossed-education using a tilt table task-oriented approach in subjects
      with post-stroke hemiplegia: A randomized controlled trial.
AB  - OBJECTIVE: To determine the effect of crossed-education, using task-related
      training on a tilt table, on upper extremity function and grip strength in
      subjects with post-stroke hemiplegia. DESIGN: Double-blind, randomized
      controlled, pilot study. PATIENTS: A total of 45 patients between 6 and 12 months
      post-stroke. METHODS: Subjects were randomly allocated to the control group, or
      experimental group I or II. All subjects received conventional upper limb
      training for 30 min, 3 times a week for 6 weeks, and training on 3 different tilt
      table applications for 20 min a day. The outcome was evaluated using the Fugl
      Meyer scale, Wolf Motor Function Test, and measurements of grip strength using a
      hydraulic hand dynamometer, prior to and 6 weeks post-intervention. RESULTS:
      There was a significantly greater increase, post-test, in the Fugl-Meyer scale (p
      = 0.003), maximal grip strength of the affected hand (p = 0.04), and grip
      strength, compared with the less-affected hand (p = 0.03), in subjects who
      underwent supplementary task-oriented training on a tilt table compared with
      those in the control group. There was also a significantly greater increase in
      Wolf Motor Function score (p = 0.001), post-test, in subjects who underwent task
      oriented training on a tilt table compared with those in the 2 experimental
      groups. CONCLUSION: Compared with tilt table or conventional training alone,
      crossed-education using task-oriented training on a tilt table may result in
      improvements in arm function and maximal grip strength in persons with chronic
      hemiplegia post-stroke.

PMID- 30221306
TI  - Children of Parents with Eating Disorders.
AB  - PURPOSE OF REVIEW: Our primary goal in this article is to review recent findings
      (from 2015 and on) concerning children of parents with eating disorders. This
      review addresses the question of whether the offspring of parents with past or
      present eating disorders have adverse outcomes. This update is timely and
      informative because recent research includes controlled studies and large cohort
      designs and earlier reviews relied on case report evidence. RECENT FINDINGS:
      Despite substantial diversity in study design, sample size, and parental eating
      disorder definition, overall, existing research suggests that the children of
      parents with eating disorders exhibit compromised development: a greater risk of
      perinatal complications; a tendency toward extremes of growth at birth; greater
      problems in feeding and eating behaviors and greater incidence of eating disorder
      symptoms; more psychological and socioemotional difficulties; and more negative
      qualities to parent-child interactions. Data on children's cognitive outcomes is
      thus far inconsistent. Given the relatively high incidence of eating disorder
      history in individuals of childbearing age, research into its potential effects
      on children is necessary. However, the methodological shortcomings and a limited
      evidence base caution in drawing conclusions. Nevertheless, mental health
      services should address the possible problems that these children face and offer
      tailored programs.

PMID- 30221307
TI  - PTSD in Children Below the Age of 6 Years.
AB  - PURPOSE OF REVIEW: This review summarizes the latest evidence and developments in
      the validation of PTSD diagnostic criteria for children 6 years and under
      (PTSD<6Y), discusses the limitations of the current diagnostic criteria, and
      highlights areas for future research. RECENT FINDINGS: Research has found that
      the DSM-5 PTSD<6Y, and a similar version in the DC:0-5, currently provides the
      most developmentally sensitive classification of PTSD for young children. In
      contrast, preliminary evidence suggests that the ICD-11 criteria might not
      appropriately capture PTSD in young children. The inclusion of PTSD<6Y, the first
      developmental subtype in the DSM-5, represents an important step towards having a
      diagnostic system that is developmentally sensitive and relevant across the life
      span. However, further validation work and research with regard to the definition
      of trauma and functional impairment as well as with the age-appropriate
      description of symptoms is needed, especially in the youngest age group (0-3
      years).

PMID- 30221309
TI  - Long-term antimicrobial assessment of orthodontic brackets coated with nitrogen
      doped titanium dioxide against Streptococcus mutans.
AB  - BACKGROUND: The antimicrobial properties of orthodontic wire and brackets with
      nitrogen-doped titanium dioxide (N-doped TiO2) coating have been studied in the
      past. However, the evaluation period had been short and limited to 30 days. The
      aim of the present study was to extend the evaluation period (up to 90 days) of
      assessing the long-term antimicrobial effects of stainless steel orthodontic
      brackets coated with nitrogen-doped titanium dioxide (N-doped TiO2). METHODS: A
      total of 40 stainless steel pre-adjusted premolar brackets were equally divided
      into two groups; namely the control group (n=20, uncoated brackets) and the
      experimental group (n=20, coated brackets). RF magnetron sputtering was used to
      apply a thin film of TiO2 on the bracket surface. The crystalline structure of
      the thin film was assessed using X-ray diffraction. The antimicrobial property of
      the brackets against Streptococcus mutans (S. mutans) was evaluated using the
      survival rate by colony-forming units (CFU) at four intervals: 24 hours (T0), 30
      days (T1), 60 days (T2), and 90 days (T3). 2-way ANOVA Repeated Measures was used
      to compare the effects between the groups over the time. RESULTS: There was no
      significant interaction between group and time (p = 0.568). The orthodontic
      brackets coated with the N-doped TiO2 thin film showed a significant CFU
      reduction (37.71 +/- 5.21, 37.81 +/- 5.03, 37.98 +/- 5.37, and 37.74 +/- 5.21 at
      T0, T1, T2, and T3, respectively) compared to the uncoated brackets (400.91 +/-
      14.67, 401.58 +/- 14.01, 400.31 +/- 14.68, and 402.04 +/- 13.98 at T0, T1, T2,
      and T3, respectively) through visible light (p < 0.001). CONCLUSION: N-doped TiO2
      coated orthodontic brackets showed strong antimicrobial property against S.
      mutans over a period of 90 days, which is effective in preventing enamel
      decalcification during orthodontic therapy.

PMID- 30221308
TI  - Social Determinants of Mental Health: Where We Are and Where We Need to Go.
AB  - PURPOSE OF REVIEW: The present review synthesizes recent literature on social
      determinants and mental health outcomes and provides recommendations for how to
      advance the field. We summarize current studies related to changes in the
      conceptualization of social determinants, how social determinants impact mental
      health, what we have learned from social determinant interventions, and new
      methods to collect, use, and analyze social determinant data. RECENT FINDINGS:
      Recent research has increasingly focused on interactions between multiple social
      determinants, interventions to address upstream causes of mental health
      challenges, and use of simulation models to represent complex systems. However,
      methodological challenges and inconsistent findings prevent a definitive
      understanding of which social determinants should be addressed to improve mental
      health, and within what populations these interventions may be most effective.
      Recent advances in strategies to collect, evaluate, and analyze social
      determinants suggest the potential to better appraise their impact and to
      implement relevant interventions.

PMID- 30221311
TI  - A simple pyramid-shaped microchamber towards highly efficient isolation of
      circulating tumor cells from breast cancer patients.
AB  - Isolation and detection of circulating tumor cells (CTCs) has showed a great
      clinical impact for tumor diagnosis and treatment monitoring. Despite significant
      progresses of the existing technologies, feasible and cost-effective CTC
      isolation techniques are more desirable. In this study, a novel method was
      developed for highly efficient isolation of CTCs from breast cancer patients
      based on biophysical properties using a pyramid-shaped microchamber. Through
      optimization tests, the outlet height of 6 MUm and the flow rate of 200 MUL/min
      were chosen as the optimal conditions. The capture efficiencies of more than 85%
      were achieved for cancer cell lines (SKBR3, BGC823, PC3, and H1975) spiked in
      DMEM and healthy blood samples without clogging issue. In clinic assay, the
      platform identified CTCs in 13 of 20 breast cancer patients (65%) with an average
      of 4.25 +/- 4.96 CTCs/2 mL, whereas only one cell was recognized as CTC in 1 of
      15 healthy blood samples. The statistical analyses results demonstrated that both
      CTC positive rate and CTC counts were positive correlated with TNM stage (p <
      0.001; p = 0.02, respectively). This microfluidic platform successfully
      demonstrated the clinical feasibility of CTC isolation and would hold great
      potential of clinical application in predicting and monitoring the prognosis of
      cancer patients.

PMID- 30221310
TI  - Neurocognitive and Information Processing Biases in Posttraumatic Stress
      Disorder.
AB  - PURPOSE OF REVIEW: We review recent research addressing neurocognitive and
      information processing abnormalities in posttraumatic stress disorder (PTSD),
      including studies informing direction of causality. We additionally consider
      neurocognition in the context of co-morbid mild traumatic brain injury (TBI) and
      psychosocial treatments for PTSD. RECENT FINDINGS: Learning, memory, attention,
      inhibitory functions, and information processing biases frequently accompany
      PTSD, reflecting potential bi-directional relationships with PTSD. Although mild
      TBI is associated with increased risk of PTSD development and maintenance, TBI
      does not typically contribute significantly to sustained neurocognitive deficits
      in individuals with PTSD. Whereas better learning and memory is associated with
      mildly enhanced response to psychosocial interventions, such interventions may
      also improve neurocognitive performance and can be effectively provided to
      patients with TBI history. PTSD is associated with cognitive abnormalities in
      processing both emotionally relevant and emotionally neutral information and,
      although mild, may underlie some PTSD symptom expression.

PMID- 30221313
TI  - How to do things with metaphors: engineering life as hodgepodge.
AB  - This paper presents a collaboration between social scientists and a chemist
      exploring the promises for new therapy development at the intersection between
      synthetic biology and nanotechnology. Drawing from ethnographic studies of
      laboratories and a recorded discussion between the three authors, we interrogate
      the metaphors that underpin what Mackenzie (Futures 48:5-12 2013) has identified
      as a recursive relationship in the iconography of the life sciences and its
      infrastructure. Focusing specifically on the use of gene editing techniques in
      synthetic biology and bio-nanotechnology, we focus our analysis on the key
      metaphors of 'evolutionary life as hodge-podge' within which 'cutting' of DNA and
      the 'sticking' and 'binding' of engineered particles to proteins can be performed
      by researchers in laboratory settings. Taken together, we argue that these
      metaphors are consequential for understanding metaphors of life-as-machine and
      the prevalence of notions of 'engineering life'. Exploring the ways in which
      notions of cutting, targeting and life as an evolutionary hodgepodge prefigure a
      more contingent notion of engineering and synthesis we close by considering the
      interpretive implications for ethnomethodological approaches to contemporary life
      science research.

PMID- 30221314
TI  - Correction to: Multi-center, randomized, double-blind, placebocontrolled study of
      quetiapine extended-release formulation in Japanese patients with bipolar
      depression.
AB  - The original version of this article contained a mistake in Table 5. Correct
      version is presented here.

PMID- 30221312
TI  - Combined lung and brain ultrasonography for an individualized "brain-protective
      ventilation strategy" in neurocritical care patients with challenging ventilation
      needs.
AB  - When intracranial hypertension and severe lung damage coexist in the same
      clinical scenario, their management poses a difficult challenge, especially as
      concerns mechanical ventilation management. The needs of combined lung and brain
      protection from secondary damage may conflict, as ventilation strategies commonly
      used in patients with ARDS are potentially associated with an increased risk of
      intracranial hypertension. In particular, the use of positive end-expiratory
      pressure, recruitment maneuvers, prone positioning, and protective lung
      ventilation can have undesirable effects on cerebral physiology: they may
      positively or negatively affect intracranial pressure, based on the final
      repercussions on PaO2 and cerebral perfusion pressure (through changes in cardiac
      output, mean arterial pressure, venous return, PaO2 and PaCO2), also according to
      the baseline conditions of cerebral autoregulation. Lung ultrasound (LUS) and
      brain ultrasound (BUS, as a combination of optic nerve sheath diameter assessment
      and cerebrovascular Doppler ultrasound) have independently proven their potential
      in respectively monitoring lung aeration and brain physiology at the bedside. In
      this narrative review, we describe how the combined use of LUS and BUS on
      neurocritical patients with demanding mechanical ventilation needs can contribute
      to ventilation management, with the aim of a tailored "brain-protective
      ventilation strategy."

PMID- 30221315
TI  - Thiophene Syntheses by Ring Forming Multicomponent Reactions.
AB  - Thiophenes occur as important building blocks in natural products, pharmaceutical
      active compounds, and in materials for electronic and opto-electronic devices.
      Therefore, there is a considerable demand for efficient synthetic strategies for
      producing these compounds. This review focuses on ring-forming multicomponent
      reactions for synthesizing thiophenes and their derivatives.

PMID- 30221316
TI  - Application of the Severity Factor and HMF Removal of Red Macroalgae Gracilaria
      verrucosa to Production of Bioethanol by Pichia stipitis and Kluyveromyces
      marxianus with Adaptive Evolution.
AB  - Gracilaria verrucosa, red seaweed, is a promising biomass for bioethanol
      production due to its high carbohydrate content. The optimal hyper thermal (HT)
      acid hydrolysis conditions are 12% (w/v) G. verrucosa with 0.2 M H2SO4 at 130 
      degrees C for 15 min, with a severity factor of 1.66. This HT acid hydrolysis
      produces 50.7 g/L monosaccharides. The maximum monosaccharide concentration of
      58.0 g/L was achieved with 96.6% of the theoretical monosaccharide production
      from 120 g dry weight/L G. verrucosa slurry after HT acid hydrolysis and
      enzymatic saccharification. Fermentation was carried out by removing an
      inhibitory compound and via yeast adaptation to galactose. Both Pichia stipitis
      and Kluyveromyces marxianus adapted to galactose were excellent producers, with
      the ethanol yield (YEtOH) of 0.50 and 29.0 g/L ethanol production. However, the
      bioethanol productivity with Pichia stipitis adapted to galactose is higher than
      that with Kluyveromyces marxianus adapted to galactose, being 0.81 and 0.35
      g/L/h, respectively. The results from this study can be applied to industrial
      scale bioethanol production from seaweed.

PMID- 30221317
TI  - Teen driver system modeling: a tool for policy analysis.
AB  - BACKGROUND: Motor vehicle crashes remain the leading cause of teen deaths in
      spite of preventive efforts. Prevention strategies could be advanced through new
      analytic approaches that allow us to better conceptualize the complex processes
      underlying teen crash risk. This may help policymakers design appropriate
      interventions and evaluate their impacts. METHODS: System Dynamics methodology
      was used as a new way of representing factors involved in the underlying process
      of teen crash risk. Systems dynamics modeling is relatively new to public health
      analytics and is a promising tool to examine relative influence of multiple
      interacting factors in predicting a health outcome. Dynamics models use explicit
      statements about the process being studied and depict how the elements within the
      system interact; this usually leads to discussion and improved insight. A Teen
      Driver System Model was developed by following an iterative process where causal
      hypotheses were translated into systems of differential equations. These
      equations were then simulated to test whether they can reproduce historical teen
      driving data. The Teen Driver System Model that we developed was calibrated on 47
      newly-licensed teen drivers. These teens were recruited and followed over a
      period of 5-months. A video recording system was used to gather data on their
      driving events (elevated g-force, near-crash, and crash events) and miles
      traveled. RESULTS: The analysis suggests that natural risky driving improvement
      curve follows a course of a slow improvement, then a faster improvement, and
      finally a plateau: that is, an S-shaped decline in driving events. Individual
      risky driving behavior depends on initial risk and driving exposure. Our analysis
      also suggests that teen risky driving improvement curve is created endogenously
      by several feedback mechanisms. A feedback mechanism is a chain of variables
      interacting with each other in such a way they form a closed path of cause and
      effect relationships. CONCLUSIONS: Teen risky driving improvement process is
      created endogenously by several feedback mechanisms. The model proposed in the
      present article to reflect this improvement process can spark discussion, which
      may pinpoint to additional processes that can benefit from further empirical
      research and result in improved insight.

PMID- 30221319
TI  - Heterogeneity of gestational diabetes (GDM) and challenges in developing a GDM
      risk score.
AB  - AIMS: Gestational diabetes (GDM) affects a growing number of women and
      identification of individuals at risk, e.g., with risk prediction models, would
      be important. However, the performance of GDM risk scores has not been optimal.
      Here, we assess the impact of GDM heterogeneity on the performance of two top
      rated GDM risk scores. METHODS: This is a substudy of the RADIEL trial-a
      lifestyle intervention study including women at high GDM risk. We assessed the
      GDM risk score by Teede and that developed by Van Leeuwen in our high-risk cohort
      of 510 women. To investigate the heterogeneity of GDM, we further divided the
      women according to GDM history, BMI, and parity. With the goal of identifying
      novel predictors of GDM, we further analyzed 319 women with normal glucose
      tolerance in the first trimester. RESULTS: Both risk scores underestimated GDM
      incidence in our high-risk cohort. Among women with a BMI >= 30 kg/m2 and/or
      previous GDM, 49.4% developed GDM and 37.4% received the diagnosis already in the
      first trimester. Van Leeuwen score estimated a 19% probability of GDM and Teede
      succeeded in risk identification in 61%. The lowest performance of the risk
      scores was seen among the non-obese women. Fasting plasma glucose, HbA1c, and
      family history of diabetes were predictors of GDM in the total study population.
      Analysis of subgroups did not provide any further information. CONCLUSIONS: Our
      findings suggest that the marked heterogeneity of GDM challenges the development
      of risk scores for detection of GDM.

PMID- 30221318
TI  - Attention-Deficit/Hyperactivity Disorder and Transitional Aged Youth.
AB  - PURPOSE OF REVIEW: Extensive research has been conducted on attention
      deficit/hyperactivity disorder (ADHD) in children and adults; however, less is
      known about ADHD during the transition from childhood to adulthood. Transitional
      aged youth (TAY) with ADHD represents a particularly vulnerable population as
      their newfound independence and responsibility often coincides with the
      development of comorbid disorders. The purpose of this review is to provide an
      update on the evaluation, diagnosis, and treatment of TAY-ADHD. RECENT FINDINGS:
      Recent studies discovering ADHD symptoms emerging in TAY call the classification
      of ADHD as a disorder necessarily developing in childhood into question. TAY-ADHD
      are also shown to be vulnerable to academic and social impairments, increased
      risky behavior, and comorbid psychiatric disorders. Due to the risk of stimulant
      diversion in TAY, providers are advised to take precaution when prescribing
      medication to this population. Recent studies demonstrating the efficacy of
      psychotherapy in conjunction with non-stimulant or extended release stimulant
      medication provide a feasible alternative. This review highlights research on the
      course and evaluation of ADHD, impairments and comorbidities specific to TAY, and
      treatments tailored to address the unique challenges associated with TAY-ADHD.

PMID- 30221321
TI  - Negative pressure wound therapy in the treatment of diabetic foot ulcers may be
      mediated through differential gene expression.
AB  - AIMS: Negative pressure wound therapy (NPWT) has been successfully used as a
      treatment for diabetic foot ulceration (DFU). Its mechanism of action on the
      molecular level, however, is not fully understood. We assessed the effect of NPWT
      on gene expression in patients with type 2 diabetes (T2DM) and DFU. METHODS: We
      included two cohorts of patients-individuals treated with either NPWT or standard
      therapy. The assignment to NWPT was non-randomized and based on wound
      characteristics. Differential gene expression profiling was performed using
      Illumina gene expression arrays and R Bioconductor pipelines based on the 'limma'
      package. RESULTS: The final cohort encompassed 21 patients treated with NPWT and
      8 with standard therapy. The groups were similar in terms of age (69.0 versus
      67.5 years) and duration of T2DM (14.5 versus 14.4 years). We identified four
      genes differentially expressed between the two study arms post-treatment, but not
      pre-treatment: GFRA2 (GDNF family receptor alpha-2), C1QBP (complement C1q
      binding protein), RAB35 (member of RAS oncogene family) and SYNJ1 (synaptic
      inositol 1,4,5-trisphosphate 5-phosphatase 1). Interestingly, all four genes
      seemed to be functionally involved in wound healing by influencing re
      epithelialization and angiogenesis. Subsequently, we utilized co-expression
      analysis in publicly available RNA-seq data to reveal the molecular functions of
      GFRA2 and C1QBP, which appeared to be through direct protein-protein
      interactions. CONCLUSIONS: We found initial evidence that the NPWT effect on DFUs
      may be mediated through differential gene expression. A discovery of the specific
      molecular mechanisms of NPWT is potentially valuable for its clinical application
      and development of new therapies.

PMID- 30221322
TI  - Tea waste derived activated carbon for the adsorption of sodium diclofenac from
      wastewater: adsorbent characteristics, adsorption isotherms, kinetics, and
      thermodynamics.
AB  - The present experimental study reports the performance of tea waste (TW) derived
      adsorbent for the adsorption of sodium diclofenac (SD) from aqueous solution (SD
      concentration = 10-50 mg/L). The waste-derived activated carbon was prepared by
      chemical activation process of raw waste using H2SO4, KOH, ZnCl2, and K2CO3 as
      activating agents (TW: activating agent = 1:1 by weight). Subsequently, the oven
      dried material was carbonized at 600- degrees C temperature for 2 h. The
      synthesized adsorbents were porous and their Brunauer-Emmett-Teller (BET) surface
      area was ranged 115-865 m2/g. Among all synthesized adsorbents, the adsorbent
      activated by ZnCl2 exhibited the highest adsorption capacity (= 62 mg/g), though
      it was much lower compared to 91 mg/g obtained with commercial activated carbon
      (CAC) (SD concentration = 30 mg/L, adsorbent dose = 300 mg/L and initial
      wastewater pH = 6.47). SD equilibrium data could be described by Langmuir
      isotherm adequately, while pseudo-second-order rate model showed better fit to
      the time based adsorption data. Low activation energy of the adsorption process
      suggests the reaction to be temperature independent. Thermodynamic parameters
      showed the spontaneous and endothermic nature of adsorption process conducted in
      the presence of waste derived adsorbent.

PMID- 30221320
TI  - The risk stratification of adverse neonatal outcomes in women with gestational
      diabetes (STRONG) study.
AB  - AIMS: To assess the risk of adverse neonatal outcomes in women with gestational
      diabetes (GDM) by identifying subgroups of women at higher risk to recognize the
      characteristics most associated with an excess of risk. METHODS: Observational,
      retrospective, multicenter study involving consecutive women with GDM. To
      identify distinct and homogeneous subgroups of women at a higher risk, the
      RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736
      pregnancies complicated by GDM were analyzed. The main outcome measure was the
      occurrence of adverse neonatal outcomes in pregnancies complicated by GDM.
      RESULTS: Among study participants (median age 36.8 years, pre-gestational BMI
      24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was
      recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59
      3.87), large for gestational age (OR 3.99, 95% CI 2.40-6.63), fetal malformation
      (OR 2.66, 95% CI 1.00-7.18), and respiratory distress (OR 4.33, 95% CI 1.33
      14.12) was associated with previous macrosomia. Large for gestational age was
      also associated with obesity (OR 1.46, 95% CI 1.00-2.15). Small for gestational
      age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04
      3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02
      2.27) and obesity (OR 1.62, 95% CI 1.04-2.51). The RECPAM analysis identified
      high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95%
      CI 1.21-2.33 for obese; OR 1.38 95% CI 1.03-1.87 for overweight). CONCLUSIONS: A
      deep investigation on the factors associated with adverse neonatal outcomes
      requires a risk stratification. In particular, great attention must be paid to
      the prevention and treatment of obesity.

PMID- 30221323
TI  - Perceptions and experiences of appetite awareness training among African-American
      women who binge eat.
AB  - INTRODUCTION: Binge eating may contribute to the prevalence of obesity in African
      American women. Yet, there has been scant intervention research on the treatment
      of binge eating in this population. We tested the feasibility of an appetite
      awareness training (AAT) intervention in a sample of African-American women with
      binge and overeating behaviors. Participants who completed AAT were recruited to
      participate in focus groups to elicit information about their perceptions and
      experiences with this intervention to inform the design of future interventions
      to treat binge eating and obesity in African-American women. METHODS: African
      American women, aged 18-70 years, who had completed an 8-week randomized AAT
      intervention, were invited to attend a focus group discussion. Session content
      was recorded and transcribed. Data were analyzed by use of open coding. Themes
      were identified that described their perceptions and experiences of participating
      in the intervention. RESULTS: Seventeen women participated in three focus group
      discussions. Pertinent themes identified included: paying attention to internal
      cues of hunger and satiety, influence of culture on eating patterns, breaking
      patterns of disordered eating, and perceptions about weight. Overall,
      participants were satisfied with their experience of AAT, and reported they found
      it valuable to learn about listening to biological signals of hunger and satiety
      and to learn specific strategies to reduce maladaptive eating patterns.
      CONCLUSION: AAT was acceptable and provided helpful eating behavior instruction
      to African-American women with reported binge and overeating behaviors. Future
      research should examine the potential of AAT to improve weight management in this
      underserved population. LEVEL OF EVIDENCE: Level V, qualitative descriptive
      study.

PMID- 30221324
TI  - High prevalence of shoplifting in patients with eating disorders.
AB  - PURPOSE: Shoplifting, prevalent in patients diagnosed with bulimia nervosa (BN),
      is a serious behavioral problem in eating disorder (ED) patients. However, little
      is known about its overall presence, etiology, and consequences. This study aimed
      to determine whether shoplifting occurs before or after the onset of ED and to
      investigate the prevalence and correlates of shoplifting in ED patients. METHODS:
      This was a cross-sectional study of 284 treatment-seeking female patients aged 13
      45 with EDs [171 anorexia nervosa (AN); 113 BN]. Shoplifting, impulsive behaviors
      (self-injury, suicide attempt, sexual promiscuity, alcohol, and illicit drug
      use), depression, self-esteem, and clinical features of EDs were assessed with an
      interview. RESULTS: Lifetime shoplifting prevalence was 28.5% (81/284) with 70.4%
      (57/81) occurring before ED onset. Multivariate logistic regression analysis
      revealed that depression [odds ratio (OR), 2.63; 95% confidence interval (CI),
      1.24-5.60], alcohol abuse (OR, 3.91; 95% CI 1.34-11.38), illicit substance use
      (OR, 14.42; 95% CI, 1.65-125.86), and self-esteem (OR, 0.90; 95% CI; 0.82-0.99)
      were associated with lifetime shoplifting, while illness duration, BN, and ED
      symptom severity were not. CONCLUSIONS: Shoplifting is common in ED patients and
      precedes ED onset in most patients with a shoplifting history, although the
      causal relationship between shoplifting and EDs remains inconclusive. Shoplifting
      may be associated with impulsive behaviors (e.g., alcohol and illicit drug use),
      depression, and low self-esteem, but not with ED severity. Future research should
      focus on the unrecognized role of shoplifting as a marker to identify patients at
      risk of impulsive behaviors and consider treatment options. LEVEL OF EVIDENCE:
      Level V, observational cross-sectional descriptive study.

PMID- 30221325
TI  - Bacterial biofilm formation inside colonic crypts may accelerate colorectal
      carcinogenesis.
AB  - BACKGROUND: Research in the field of relation between microbes and colorectal
      carcinogenesis has gained increasing interest in past years. Recently, link
      between microbial biofilm and carcinogenesis in colon was demonstrated by several
      authors indicating that biofilm not only is a key player in carcinogenesis, but
      also may contribute to the understanding of side-specific colon cancer-right
      sided colon cancer versus left sided. In this article, we briefly highlight the
      major findings of the research of biofilm and carcinogenesis and demonstrate our
      findings of colonic cancer tissue and colonic polyp examined for biofilm. CASE
      PRESENTATION: Colonic cancer tissue from a patient with a right-sided colon
      cancer, and an adenoma tubular polyp were examined for biofilm formation by
      flourescens in situ hybridization. In cancer tissue we found biofilm formation on
      the surface epithelium but surprisingly also deep into the crypts. No biofilms
      were found in tubular polyp tissue. CONCLUSIONS: To our knowledge, this is the
      first-time biofilm formation deep into colonic crypts are demonstrated in a
      patient with right-sided colon cancer. This may indicate that bacterial biofilm
      may have a key role in carcinogenesis.

PMID- 30221326
TI  - Community structure of metazoan parasites from Pimelodus blochii in two rivers of
      the Western Brazilian Amazon: same seasonal traits, but different anthropogenic
      impacts.
AB  - The present investigation evaluated the influence of seasonality and locality on
      the structure of the parasite community of the catfish Pimelodus blochii. A total
      of 160 fish were collected from two rivers in the State of Acre, western
      Brazilian Amazon: 80 fish in River Acre and 80 in River Iaco, with 40 in each
      season (rainy and drought). The overall prevalence was 78.7% and 1461 parasite
      specimens (adults and larvae) were allocated in 22 taxa: 5 of Monogenea, 10 of
      Nematoda, 3 of Digenea, 1 of Cestoda and 3 of Crustacea. In drought season,
      Procamallanus (Spirocamallanus) pimelodus and Demidospermus peruvianus were more
      prevalent in River Acre and Iaco, respectively. The parasite diversity (Brillouin
      index) as well as the prevalence and abundance of the monogeneans D. peruvianus,
      D. striatus, Demidospermus sp. and Ameloblastella sp. were higher in River Acre.
      The parasite community structure were dissimilar among rivers, and seasonally in
      River Iaco. These results suggest that environmental traits may overshadow
      seasonal influences on the parasite community structure, which may be related to
      the higher anthropization in River Acre. Furthermore, seasonality exerted less
      influence on the parasite community than expected, probably because the two
      rivers have different hydrological traits than those of other rivers in the
      Brazilian Amazon. New host and locality records expanded our knowledge of
      parasite biodiversity of P. blochii.

PMID- 30221327
TI  - Diagnosis and differential diagnosis of large-vessel vasculitides.
AB  - There are no universally accepted diagnostic criteria for large-vessel
      vasculitides (LVV), including giant cell arteritis (GCA) and Takayasu arteritis
      (TAK). Currently, available classification criteria cannot be used for the
      diagnosis of GCA and TAK. Early diagnosis of these two diseases is quite
      challenging in clinical practice and may be accomplished only by combining the
      patient symptoms, physical examination findings, blood test results, imaging
      findings, and biopsy results, if available. Awareness of red flags which lead the
      clinician to investigate TAK in a young patient with persistent systemic
      inflammation is helpful for the early diagnosis. It should be noted that clinical
      presentation may be highly variable in a subgroup of GCA patients with
      predominant large-vessel involvement (LVI) and without prominent cranial
      symptoms. Imaging modalities are especially helpful for the diagnosis of this
      subgroup. Differential diagnosis between older patients with TAK and this
      subgroup of GCA patients presenting with LVI may be difficult. Various
      pathologies may mimic LVV either by causing systemic inflammation and
      constitutional symptoms, or by causing lumen narrowing with or without aneurysm
      formation in the aorta and its branches. Differential diagnosis of aortitis is
      crucial. Infectious aortitis including mycotic aneurysms due to septicemia or
      endocarditis, as well as causes such as syphilis and mycobacterial infections
      should always be excluded. On the other hand, the presence of non-infectious
      aortitis is not unique for TAK and GCA. It should be noted that aortitis, other
      large-vessel involvement or both, may occasionally be seen in various other
      autoimmune pathologies including ANCA-positive vasculitides, Behcet's disease,
      ankylosing spondylitis, sarcoidosis, and Sjogren's syndrome. Besides, aortitis
      may be idiopathic and isolated. Atherosclerosis should always be considered in
      the differential diagnosis of LVV. Other pathologies which may mimic LVV include,
      but not limited to, congenital causes of aortic coarctation and middle aortic
      syndrome, immunoglobulin G4-related disease, and hereditary disorders of
      connective tissue such as Marfan syndrome and Ehler-Danlos syndrome.

PMID- 30221328
TI  - Posttraumatic Stress Disorder and Death From Suicide.
AB  - PURPOSE OF REVIEW: This review summarizes the increasing public health concern
      about PTSD and suicide, and the population-based studies that have examined this
      association. Further, we discuss methodological issues that provide important
      context for the examination of this association. RECENT FINDINGS: The majority of
      epidemiologic studies have shown that PTSD is associated with an increased risk
      of suicide; however, a notable minority of studies have documented a decreased
      risk of suicide among persons with PTSD. Methodological (e.g., sample size and
      misclassification) and etiologic issues (e.g., complicated psychiatric
      comorbidity) may explain the conflicting evidence. PTSD may be associated with an
      increased risk of suicide, but further research is needed. Increasing the use of
      appropriate methods (e.g., marginal structural models that can evaluate both
      confounding and effect modification, machine learning methods, quantification of
      systematic error) will strengthen the evidence base and advance our
      understanding.

PMID- 30221330
TI  - Similar thromboprophylaxis with rivaroxaban and low molecular weight heparin but
      fewer hemorrhagic complications with combined intra-articular and intravenous
      tranexamic acid in total knee arthroplasty.
AB  - PURPOSE: To evaluate the efficacy of the combined intravenous and intra-articular
      administration of tranexamic acid (TXA) to control the collateral effects and
      complications of rivaroxaban (RIV) after total knee arthroplasty (TKA) and to
      compare thromboprophylaxis schemes with and without TXA, RIV and low molecular
      weight heparin (LMWH). MATERIALS AND METHODS: We prospectively studied 158 TKA
      patients from 2014 to 2018. The patients were randomly assigned into three
      groups. Group A (46 patients) was administered intravenous and intra-articular
      TXA and RIV postoperatively; group B (58 patients) was administered TXA as in
      group A and LMWH postoperatively; and group C (54 patients) was administered
      saline as in group A and RIV postoperatively. We evaluated blood loss,
      transfusion requirements and hemorrhagic complications. RESULTS: Hct and Hb
      values significantly decreased in group C compared to groups A and B, without any
      difference between groups A and B. Suction drain blood volume output was
      significantly higher in group C compared to group A and B, without any difference
      between group A and B. Hemorrhagic complications were more common in group C. No
      patient experienced clinical findings of VTE. CONCLUSION: Combined intravenous
      and intra-articular administration of TXA is safe and effective in TKA, with
      fewer hemorrhagic complications compared to placebo. Thromboprophylaxis with RIV
      and LMWH is similar.

PMID- 30221329
TI  - Correction to: a risk stratification model for nodal peripheral T-cell lymphomas
      based on the NCCN-IPI and posttreatment Deauville score.
AB  - Unfortunately, the original version of this article contained several errors made
      during final step of article production. In the results section (fourth sentence)
      of the Abstract, the incomplete sentence,", 31.4% in high-risk group and 4.7% in
      treatment failure group.

PMID- 30221331
TI  - Phytochemical Background Mediates Effects of Pyrrolizidine Alkaloids on Western
      Flower Thrips.
AB  - Plants produce an extremely diverse array of metabolites that mediate many
      aspects of plant-environment interactions. In the context of plant-herbivore
      interactions, it is as yet poorly understood how natural backgrounds shape the
      bioactivity of individual metabolites. We tested the effects of a methanol
      extract of Jacobaea plants and five fractions derived from this extract, on
      survival of western flower thrips (WFT). When added to an artificial diet, the
      five fractions all resulted in a higher WFT survival rate than the methanol
      extract. In addition, their expected combined effect on survival, assuming no
      interaction between them, was lower than that of the methanol extract. The
      bioactivity was restored when the fractions were combined again in their original
      proportion. These results strongly suggest synergistic interactions among the
      fractions on WFT survival rates. We then tested the effects of two pyrrolizidine
      alkaloids (PAs), free base retrorsine and retrorsine N-oxide, alone and in
      combination with the five shoot fractions on WFT survival. The magnitude of the
      effects of the two PAs depended on the fraction to which they were added. In
      general, free base retrorsine was more potent than retrorsine N-oxide, but this
      was contingent on the fraction to which these compounds were added. Our results
      support the commonly held, though seldom tested, notion that the efficacy of
      plant metabolites with respect to plant defence is dependent on their
      phytochemical background. It also shows that the assessment of bioactivity cannot
      be decoupled from the natural chemical background in which these metabolites
      occur.

PMID- 30221332
TI  - Examining the Relationship Between Neurosteroids, Cognition, and Menopause With
      Neuroimaging Methods.
AB  - PURPOSE OF REVIEW: Previous literature has shown inconsistent findings regarding
      the effects of neurosteroids on the brain in postmenopausal women. The goal of
      this paper is to examine how and whether advances in neuroimaging have helped
      elucidate the relationship between the withdrawal of and/or treatment with
      neurosteroids and cognition at menopause. RECENT FINDINGS: Neuroimaging
      techniques such as structural and functional MRI have been used in recent studies
      to examine the relationship between neurosteroids and brain structure and
      functioning. However, the recent literature shows that different formulations of
      postmenopausal hormones given at different times, through different routes of
      administration, and in different combinations with progestins result in a variety
      of relationships with the brain outcomes. We suggest that still further research
      is needed to understand how the structural changes resulting from estrogen
      withdrawal or therapy at menopause can influence cognitive functioning. However,
      imaging studies are time-, resource-, and expertise-intensive. We believe that
      this information will help uncover the mechanisms and relationships that can aid
      in the explanation of the individual differences in the effects of menopause on
      the brain as well as how this menopause-related hormone change influences risk
      for pathological aging.

PMID- 30221333
TI  - Systematic Literature Review of the Economic Burden of Celiac Disease.
AB  - BACKGROUND: The prevalence of celiac disease (CD) has rapidly increased over
      recent decades, but costs related to CD remain poorly quantified. OBJECTIVE: This
      systematic review assessed the economic burden of CD in North America and Europe.
      METHODS: MEDLINE, EMBASE, EconLit, and the Cochrane Library databases were
      systematically searched to identify English-language literature from 2007 to 2018
      that assessed costs, cost effectiveness, and health resource utilization for CD.
      RESULTS: Forty-nine studies met the inclusion criteria, of which 28 (57.1%)
      addressed costs of testing and diagnosis; 33 (67.3%) were from Europe. The cost
      per positive CD diagnosis of testing patients already undergoing
      esophagogastroduodenoscopy for other indications ranged from 1300 Canadian
      dollars ($Can) in Canada (2016 value) to ?44,712 in the Netherlands (2013 value).
      Adding the CD test was cost effective when it combined diagnostic modalities
      (e.g., serology and biopsy). Direct annual excess costs to a US payer per
      diagnosed CD patient totaled $US6000 (2013 value) more than for a person without
      CD, chiefly due to outpatient care. Hospitalizations, emergency visits, and
      medication use were more common with CD. After initiating a gluten-free diet
      (GFD), patients visited primary care providers less often, used more medications,
      and missed fewer days from school and work. CONCLUSIONS: Most of the few
      available economic studies of CD assess testing and diagnosis costs, especially
      in Europe. Methods of testing generally are considered cost effective when they
      combine diagnostic modalities in symptomatic patients. Most costs to a payer of
      managing CD derive from outpatient care. Following GFD initiation, patients lose
      fewer days from work and school than pretreatment.

PMID- 30221334
TI  - MMP-1/TIMP-1 expressions in rectal submucosa of females with obstructed
      defecation syndrome associated with internal rectal prolapse.
AB  - OBJECTIVE: To explore the MMP-1/TIMP-1 expressions in rectal submucosa of females
      with obstructed defecation syndrome (ODS) associated with internal rectal
      prolapse (IRP). METHODS: Fifty-six female patients with ODS associated with IRP
      were enrolled as Case group, and 43 female hemorrhoids of stages III-IV without
      constipation and IRP were enrolled as Control group. Quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were
      performed to test the expressions of MMP-1/TIMP-1 in the rectal submucosa.
      Western blotting was used to examine protein expressions of MMP-1/TIMP-1 and pro
      inflammatory cytokines (IL-6 and TNF-alpha) in the rectal submucosa. EVG staining
      was conducted to detect collagen and elastic fibers in rectal submucosa. RESULTS:
      The increased expression of MMP-1 was negatively linked to the decreased TIMP-1
      level in the rectal submucosa of patients with ODS associated with IRP. Besides,
      the expressions of IL-6 and TNF-alpha were increased in the Case group as
      compared with the Control group. Additionally, ODS severity and the pro
      inflammatory cytokines was positively linked to MMP-1, but negatively related to
      TIMP-1 in Case group. EVG staining showed that the area ratios of collagen and
      elastic fibers were lower in Case group than Control group. Through Pearson's
      correlation analysis, the area ratios of collagen and elastic fibers were
      positively associated with MMP-1 expression, but negatively correlated with TIMP
      1 expression in rectal submucosa of patients with ODS associated with IRP.
      CONCLUSION: Elevated MMP-1 and reduced TIMP-1 were found in ODS associated with
      IRP, which was related to the ODS severity, inflammation and contents of collagen
      and elastic fibers.

PMID- 30221335
TI  - Urethral Meatus and Glanular Closure Line: Normal Biometrics and Clinical
      Significance.
AB  - :  Purpose: The aim of this study is to explore the normal external urethral
      meatal and glans closure line in normal boys, and to investigate the correlation
      between these glans biometrics and the age of the participants. MATERIAL AND
      METHOD: 103 male children were asked to participate in the study during ritual
      circumcision. Par-ents of 94 of them (mean age 5.9 years, range 0.6-13) accepted
      while remaining 9 did not. Glans biometrics were measured using digital calipers.
      RESULT: 100% of the study participants had a vertical slit-like meatal opening
      located at the tip of the glans. The length of the meatal opening was 5.3 (+/- 1)
      mm and of ventral glans closure was 4.8 (+/-1.1) mm. Significant cor-relation
      between both the external meatal opening and closure lines lengths and age was
      observed. Moreover, the meatal opening size was correlated to the glans closure
      line as well (r = 0.36, confidence interval 0.14-0.54, P < .001). CONCLUSION: The
      site and size of the meatus opening in normal male children is consistent, and
      ventral glans clo-sure is equal to or slightly less than meatal length. These
      findings could aid in glanular reconstruction configuration during hypospadias
      surgery.

PMID- 30221336
TI  - Is A Combination of Antibiotics and Non-Steroidal Anti-Inflammatory Drugs More
      Beneficial Than Antibiotic Monotherapy For The Treatment of Female Acute
      Uncomplicated Cystitis? A Randomized Controlled Pilot Study.
AB  - Purpose: To compare the efficacy of non-steroidal anti-inflammatory drugs
      (NSAIDs) combination therapy to single-agent antibiotic therapy for the
      resolution of symptoms during two restricted activity days in patients with acute
      uncomplicated cystitis (AUC)Materials and Methods: We performed a prospective,
      randomized control pilot study. A total of 55 patients were enrolled. Group I
      (n=28) was treated with cepodoxime (100 mg twice per day), and Group II (n=27)
      was treated with cepodoxime (100 mg) and aceclofenac (100 mg) twice per day; both
      groups were treated for three days. Upon dysuria after each administration, the
      participants entered a value on a numerical pain scale. The primary outcome was
      whether there were any differences in the decrease rate in pain scale between the
      two groups.Result: The average age of the 55 patients was 49.9 +/- 13.5 years,
      and prior to the clinical visit, the patients ex-perienced an average of 2.4 +/-
      2.2 days of dysuria symptoms. The average numerical pain scale score for dysuria
      was 4.98 +/- 2.18. Thirty-four patients (61.8%) showed positive culture results,
      and E. coli was the most commonly found bacteria, cultured in 32 patients.Fifty
      one patients visited the clinic on day 7, and 42 (76.4%) reported symptom
      improvement, while nine patients (16.3%) had persistent symptoms. The follow-up
      numerical pain score was 0.39 +/- 1.02 points. The pain score was dramatically
      decreased after medication. No difference was observed in the magnitude of the
      pain scale reduction between the two groups (P = 0.134). However, group II showed
      faster symptom resolution (P = 0.035) at the third administration (day
      1.5).Conclusion: Combination therapy with NSAIDs and antibiotics for AUC patients
      can improve symptoms faster during two restricted activity days when patients
      have difficulty performing daily living activities.

PMID- 30221337
TI  - Analysing the efficacy of the I-gel supraglottic airway device in the supine and
      lateral decubitus positions.
AB  - BACKGROUND: The advantages of the I-gel supraglottic airway device include ease
      and speed of insertion, reduced trauma incidence, an integral bite block, gastric
      access, a non-inflatable cuff and superior seal pressure. The primary goal of
      this study was to compare airway leak pressures and the fibreoptic view in the
      supine and lateral positions. Our secondary aim was to analyse the effects of I
      gel insertion on haemodynamic parameters. METHODS: One hundred patients
      undergoing saturation biopsy due to prostatic hyperplasia were recruited to this
      prospective randomised study. An I-gel device was inserted in the supine
      position. Taking of measurements, patients were placed in the lateral decubitus
      position. Mean arterial pressure, heart rate, peripheral O2 saturation and end
      tidal CO2 were recorded before and after insertion. We recorded the number of
      attempts and insertion time for the I-gel device. Oropharyngeal leak pressures
      and I-gel device positioning were scored in the lateral decubitus and supine
      positions. RESULTS: It was possible to insert the I-gel device in 88 patients on
      the first attempt. The median time for insertion was 7.97 +/- 2.18 sec. The mean
      arterial pressure and heart rate decreased 1 and 2 min after insertion.
      Oropharyngeal leak pressure was similar in the supine (27.45 +/- 5.37 mm Hg) and
      lateral decubitus positions (26.04 +/- 4.92 mm Hg) (P > 0.05). On fibreoptic
      examination through the I-gel device, the scores of patients were comparable in
      different positions (P = 0.542). CONCLUSION: As there was no significant
      difference in oropharyngeal leak pressure and fibreoptic view, we concluded that
      the I-gel device may be used safely in both the supine and lateral positions.

PMID- 30221338
TI  - Risk factors for occurrence of failed interscalene brachial plexus blocks for
      shoulder arthroscopy using 20 mL 0.5% ropivacaine: a randomised trial.
AB  - BACKGROUND: Adequate pain management after arthroscopic procedures improves
      patients' satisfaction with the performed procedure, as well as facilitating
      early rehabilitation. The aim of the current randomised, prospective clinical
      study was to assess the influence of anthropometric parameters and the
      interscalene brachial plexus block (IBPB) technique on the quality of post
      operational analgesia. METHODS: 109 randomly selected patients of ASA I-III
      status were scheduled for elective shoulder arthroscopy. Reasons for non
      inclusion were as follows: neurological deficit in the upper arm; allergies to
      amide Las; coagulopathy; and pregnancy. The patients received 20 mL of 0.5%
      ropivacaine for an ultrasound (US)-guided IBPB (group U), peripheral nerve
      stimulation (PNS)-confirmation IBPB (group N), or US-guided, PNS-confirmed IBPB
      (dual guidance; group NU). RESULTS: We observed that the studied groups did not
      differ in mean time of sensory and motor block terminations and, surprisingly, in
      each group in individual cases the sensory block lasted up to 890-990 minutes
      providing satisfactory long-lasting post-operational analgesia in patients
      receiving IBPB. We observed a negative correlation between BMI and termination of
      the motor block and a positive correlation between age and termination of the
      sensory block in patients receiving US-guided IBPB (group U) in comparison with
      the two other groups. We found a positive correlation between the male gender and
      termination of the motor block in patients receiving PNS-guided IBPB (group N) in
      comparison with two other groups. CONCLUSION: In our study, patients received
      satisfactory analgesia in the post-operational period no matter what technique
      was used regardless of their age, gender or potentially uncommon anthropometry.

PMID- 30221339
TI  - Ultrasound assessment of gastric emptying and the risk of aspiration of gastric
      contents in the perioperative period.
AB  - The risk of aspiration of gastric contents in the perioperative period
      constitutes a serious clinical problem and it is connected with increased
      mortality. At present, the risk of aspiration is assessed only on the basis of an
      interview and information obtained from the patient. Such assessment is not
      always reliable while the concomitance of some additional factors influencing the
      delay of gastric emptying significantly decreases its sensitivity. Using bedside
      ultrasound imaging in an assessment of gastric contents is a method which
      supports an objective, simple and quick assessment of the risk of aspiration,
      helps one to optimise perioperative anaesthetic management, and should constitute
      a routine element of the perioperative patient assessment.

PMID- 30221340
TI  - Continuous Quadratus Lumborum Block (QLB) for postoperative recurrent and chronic
      pain. Series of case reports.

PMID- 30221341
TI  - Anger, sad, and blended expressions to contingency disruption in young infants.
AB  - Three studies elicited young infants' (aged 17-23 weeks) anger and sad facial
      expressions during brief contingency disruptions to explore their potential
      organization over time as a biphasic process. Study 1 examined partial
      correlations among anger, sad, blended anger/sad, and neutral expressions during
      extinction in three extant, independently recruited samples. Across samples, all
      three negative expressions were inversely related to neutral expressions, but
      anger and sad expressions were not significantly correlated when anger/sad blends
      were controlled. Study 2 compared expressions during contingency and disruption
      minutes in two groups: one in which the disruption was an extinction phase (the
      absence of the formerly contingent event), or one in which the disruption was
      noncontingent presentations of the stimuli. Study 3 examined expression
      trajectories over time in two contingency and extinction sessions. Independent
      trajectories of anger and sad expressions occurred over time in Studies 2 and 3.
      Extinction and noncontingency differed in sad expression. The relation between
      expressions and blends also varied over time.

PMID- 30221342
TI  - Walking through doorways differentially affects recall and familiarity.
AB  - Previous research has reported that walking through a doorway to a new location
      makes memory for objects and events experienced in the previous location less
      accurate. This effect, termed the location updating effect, has been used to
      suggest that location changes are used to mark boundaries between events in
      memory: memories for objects encountered within the current event are more
      available than those from beyond an event boundary. Within a computer-generated
      memory task, participants navigated through virtual rooms, walking through
      doorways, and interacting with objects. The accuracy and their subjective
      experience of their memory for the objects (remember/know and confidence) were
      assessed. The findings showed that shifts in location decreased accurate
      responses associated with the subjective experience of remembering but not those
      associated with the experience of knowing, even when considering only the most
      confident responses in each condition. These findings demonstrate that a shift in
      location selectively impacts recollection and so contributes to our understanding
      of boundaries in event memory.

PMID- 30221343
TI  - Genomic duplication in the 19q13.42 imprinted region identified as a new genetic
      cause of intrauterine growth restriction.
AB  - We report findings from a male fetus of 26 weeks' gestational age with severe
      isolated intrauterine growth restriction (IUGR). Chromosomal microarray analysis
      (CMA) on amniotic fluid cells revealed a 1.06-Mb duplication in 19q13.42
      inherited from the healthy father. This duplication contains 34 genes including
      ZNF331, a gene encoding a zinc-finger protein specifically imprinted (paternally
      expressed) in the placenta. Study of the ZNF331 promoter by methylation-specific
      multiplex ligation-dependent probe amplification showed that the duplicated
      allele was not methylated in the fetus unlike in the father's genome, suggesting
      both copies of the ZNF331 gene are expressed in the fetus. The anti-ZNF331
      immunohistochemical analysis confirmed that ZNF331 was expressed at higher levels
      in renal and placental tissues from this fetus compared to controls.
      Interestingly, ZNF331 expression levels in the placenta have previously been
      reported to inversely correlate with fetal growth parameters. The original
      observation presented in this report showed that duplication of ZNF331 could be a
      novel genetic cause of isolated IUGR and underlines the usefulness of CMA to
      investigate the genetic causes of isolated severe IUGR.

PMID- 30221344
TI  - Population-based analysis of the impact of trauma on longer-term functional
      outcomes.
AB  - BACKGROUND: Functional outcome measures are important as most patients survive
      trauma. The aim of this study was to describe the long-term impact of trauma
      within a healthcare region from a social perspective. METHODS: People active in
      work or education and admitted to hospitals in Central Norway in the interval 1
      June 2007 to 31 May 2010 after sustaining trauma were included in the study.
      Clinical data were linked to Norwegian national registers of cause of death,
      sickness and disability benefits, employment and education. Primary outcome
      measures were receipt of medical benefits and time to return to preinjury work
      level. Secondary outcome measures were mortality within 30 days or during follow
      up. RESULTS: Some 1191 patients were included in the study, of whom 193 (16.2 per
      cent) were severely injured (Injury Severity Score greater than 15). Five years
      after injury, the prevalence of medical benefits was 15.6 per cent among workers
      with minor injuries, 22.3 per cent in those with moderate injuries and 40.5 per
      cent among workers with severe injuries. The median time after injury until
      return to work was 1, 4 and 11 months for patients with minor, moderate and
      severe injuries respectively. Twelve patients died within 30 days and an
      additional 17 (1.4 per cent) during follow-up. CONCLUSION: Patients experiencing
      minor or major trauma received high levels of medical benefits; however, most
      recovered within the first year and resumed preinjury work activity. Patients
      with severe trauma were more likely to receive medical benefits and have a
      delayed return to work. Registration number: NCT02602405
      (http://www.clinicaltrials.gov).

PMID- 30221345
TI  - Genomic screening in rare disorders: New mutations and phenotypes, highlighting
      ALG14 as a novel cause of severe intellectual disability.
AB  - We have investigated 20 consanguineous families with multiple children affected
      by rare disorders. Detailed clinical examinations, exome sequencing of affected
      as well as unaffected family members and further validation of likely pathogenic
      variants were performed. In 16/20 families, we identified pathogenic variants in
      autosomal recessive disease genes (ALMS1, PIGT, FLVCR2, TFG, CYP7B1, ALG14,
      EXOSC3, MEGF10, ASAH1, WDR62, ASPM, PNPO, ERCC5, KIAA1109, RIPK4, MAN1B1). A
      number of these genes have only rarely been reported previously and our findings
      thus confirm them as disease genes, further delineate the associated phenotypes
      and expand the mutation spectrum with reports of novel variants. We highlight the
      findings in two affected siblings with splice altering variants in ALG14 and
      propose a new clinical entity, which includes severe intellectual disability,
      epilepsy, behavioral problems and mild dysmorphic features, caused by biallelic
      variants in ALG14.

PMID- 30221346
TI  - Action-selection perseveration in young children: Advances of a dynamic model.
AB  - This study presents an empirical test and dynamic model of perseverative limb
      selection in children of 14-, 24-, and 36-months old (N = 66 in total). In the
      experiment, children repeatedly grasped a spoon with a single hand. In two
      separate conditions, the spoon was presented either four times on their right
      side or four times on their left side. In both conditions, following this
      training, the spoon was presented on midline for two more trials. This setup
      enabled us to determine whether children's limb selection was influenced by their
      prior choices in the task (i.e., perseveration). Individual children's handedness
      was determined in a third condition consisting of nine object presentations
      (laterally or on midline). A dynamic model for limb selection is presented
      combining external input, motor memory, and preferences. The model was used to
      simulate the experiment and reproduced the results, including the age-related
      changes.

PMID- 30221347
TI  - Increased developmental density decreases the magnitude of indirect genetic
      effects expressed during agonistic interactions in an insect.
AB  - The expression of aggression depends not only on the direct genetic effects
      (DGEs) of an individual's genes on its own behavior, but also on indirect genetic
      effects (IGEs) caused by heritable phenotypes expressed by social partners. IGEs
      can affect the amount of heritable variance on which selection can act. Despite
      the important roles of IGEs in the evolutionary process, it remains largely
      unknown whether the strength of IGEs varies across life stages or competitive
      regimes. Based on manipulations of nymphal densities and > 3000 pair-wise
      aggression tests across multiple life stages, we experimentally demonstrate that
      IGEs on aggression are stronger in field crickets (Gryllus bimaculatus) that
      develop at lower densities than in those that develop at higher densities, and
      that these effects persist with age. The existence of density-dependent IGEs
      implies that social interactions strongly determine the plastic expression of
      aggression when competition for resources is relaxed. A more competitive (higher
      density) rearing environment may fail to provide crickets with sufficient
      resources to develop social cognition required for strong IGEs. The contribution
      of IGEs to evolutionary responses was greater at lower densities. Our study
      thereby demonstrates the importance of considering IGEs in density-dependent
      ecological and evolutionary processes.

PMID- 30221348
TI  - Fake News: Medicines Misinformation by the Media.
AB  - Mainstream broadcasting media is a potentially powerful avenue for disseminating
      wellness education. For example, it can be used for community-based risk
      management, including preparing for pandemic events. The media can have a
      considerable positive impact on the public by increasing their health knowledge,
      changing attitudes and intentions, and influencing health behavior. However,
      although the broadcasting media can usefully convey prosocial, healthy messages,
      there is also a risk of propagating incorrect and antisocial, poor public health
      information.

PMID- 30221349
TI  - Blue lesions of the ears: When dermoscopy is not enough!

PMID- 30221350
TI  - Doug Altman's legacy to Cochrane and evidence synthesis.

PMID- 30221351
TI  - Towards validation of delay discounting in the pigeon.
AB  - A series of procedures were conducted in an attempt to assess various forms of
      validity related to the use of pigeons in research on delay discounting. In
      separate experimental arrangements, pigeons pressed a treadle, pecked a lit key,
      pecked a darkened key, or pecked a lit key with a hold as the required response.
      First, the obtained results were consistent with what would be necessary if the
      construct of delay discounting were being measured, which provides evidence of
      face validity. Second, criterion validity was assessed by comparing individual
      differences in rates of discounting across procedures. Third, to assess internal
      validity, each pigeon repeated the Treadle, Key Peck, and Dark Key procedures.
      Again, at both the aggregate and individual levels, the obtained indifference
      points did not differ systematically between replications. Finally, to assess
      external validity, discounting was observed regardless of the procedure, where
      the patterns of data at the aggregate level, and generally at the individual
      level, were orderly and well described by a hyperbolic function. In addition,
      rates of discounting were similar when pigeons pecked a lit key, a dark key, or a
      key with a hold; and each of those rates of discounting tended to be steeper than
      when treadle pressing. Generally speaking, pigeons that discounted relatively
      steeply on one procedure also tended to discount relatively steeply on the other
      procedures. The procedures evidence some of the necessary elements involved with
      the use of pigeons in research on delay discounting.

PMID- 30221353
TI  - Integrating clients' religion and spirituality within psychotherapy: A
      comprehensive meta-analysis.
AB  - Some religious or spiritual (R/S) clients seek psychotherapy that integrates R/S
      values, while others may be reticent to disclose R/S-related aspects of struggles
      in a presumably secular setting. We meta-analyzed 97 outcome studies (N = 7,181)
      examining the efficacy of tailoring treatment to patients' R/S beliefs and
      values. We compared the effectiveness of R/S-tailored psychotherapy with no
      treatment controls, alternate secular treatments, and additive secular
      treatments. R/S-adapted psychotherapy resulted in greater improvement in clients'
      psychological (g = 0.74, p < 0.000) and spiritual (g = 0.74, p < 0.000)
      functioning compared with no treatment and non R/S psychotherapies
      (psychological: g = 0.33, p < 0.001; spiritual: g = 0.43, p < 0.001). In more
      rigorous additive studies, R/S-accommodated psychotherapies were equally
      effective to standard approaches in reducing psychological distress (g = 0.13, p
      = 0.258), but resulted in greater spiritual well-being (g = 0.34, p < 0.000). We
      feature several clinical examples and conclude with evidence-based therapeutic
      practices.

PMID- 30221354
TI  - Suppression of long noncoding RNA NCK1-AS1 increases chemosensitivity to
      cisplatin in cervical cancer.
AB  - Cervical cancer remains a serious health problem till now, with nearly 500,000
      women cases diagnosed each year around the world. Long noncoding RNA (lncRNA) is
      a novel class of RNA transcripts (>200 nucleotides in length) participating in
      gene transcription, cell proliferation, differentiation, and drug resistance.
      This study aimed to explore the regulatory relationship among lncRNA NCK1-AS1,
      miR-134-5p, and MutS protein homolog 2 (MSH2), so that the resistance against
      cisplatin in cervical cancer treatment could be better understood. Comprehensive
      lncRNA profiling analysis was performed to screen lncRNAs differentially
      expressed in cervical cancer. The expression patterns of miR-134-5p, NCK1-AS1,
      and MSH2 were evaluated in cancerous tissues and adjacent normal tissues obtained
      from 75 cervical cancer patients. Subsequently, anti-NCK1-AS1 small interfering
      RNA, miR-134-5p mimics, and miR-134-5p inhibitors were transfected into cervical
      cancer cells, and the effects of these transcripts on cisplatin resistance and
      cell apoptosis were investigated. The regulatory relationship among NCK1-AS1, miR
      134-5p, and MSH2 was identified using a dual-luciferase reporter gene assay, and
      the results were further validated by RNA pull-down and RNA immunoprecipitation
      assays. Based on the microarray data of GSE63514 and GSE27678, NCK1-AS1 was
      upregulated in cervical cancer. Increased expression of NCK1-AS1, MSH2, and
      decreased expression of miR-134-5p were observed in cervical cancer tissues. In
      addition, NCK1-AS1 competitively bound to miR-134-5p to regulate MSH2. Therefore,
      si-NCK1-AS1 and miR-134-5p mimic both reduced MSH2 activity and increased
      cisplatin-induced apoptosis in cervical cancer cells. Taken together, NCK1-AS1
      may become a novel target in improving the chemotherapeutic response and survival
      of cervical cancer patients.

PMID- 30221352
TI  - Strontium ion attenuates lipopolysaccharide-stimulated proinflammatory cytokine
      expression and lipopolysaccharide-inhibited early osteogenic differentiation of
      human periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease
      characterized by the destruction of the periodontium. The strontium ion (Sr2+ )
      can prevent the bone loss associated with periodontitis and promote the
      regeneration of the bone. The mechanisms by which the Sr2+ works remain poorly
      understood. We aim to investigate the effects of the Sr2+ ion on cell
      proliferation, inflammatory regulation and osteogenic differentiation of human
      periodontal ligament cells (hPDLCs) in pathological conditions. MATERIAL AND
      METHODS: hPDLCs were obtained from premolars that came from the orthodontic
      extraction. The hPDLCs were treated with Sr2+ and/or lipopolysaccharide (LPS),
      which was applied as the pathological condition of periodontitis. The effect of
      the dose of Sr2+ on cell proliferation was analyzed using a Cell Counting Kit-8
      assay. The gene and protein expression of proinflammatory cytokines were detected
      by the real-time polymerase chain reaction and enzyme-linked immunosorbent assay.
      The osteogenic differentiation and mineralization were assessed by the real-time
      polymerase chain reaction, alkaline phosphatase activity assay and alizarin red
      staining. RESULTS: Results demonstrated that Sr2+ in a range of concentrations
      from 0.02 to 2.5 mmol/L significantly improved the proliferation of hPDLCs. Sr2+
      reversed LPS-stimulated proinflammatory cytokine expressions such as tumor
      necrosis factor alpha, interleukin (IL)-1beta, IL-6 and IL-8. Moreover, Sr2+
      rescued the LPS-inhibited gene expression of osteogenic differentiation. Although
      it appeared to suppress the late mineralization, Sr2+ can reverse the LPS
      inhibited early osteogenic differentiation of hPDLCs. CONCLUSION: These results
      indicated that Sr2+ could attenuate the LPS-stimulated proinflammatory molecule
      expression and inhibit early osteogenic differentiation of hPDLCs.

PMID- 30221356
TI  - Down-regulation of PKM2 decreases FASN expression in bladder cancer cells through
      AKT/mTOR/SREBP-1c axis.
AB  - Fatty acid synthase (FASN) catalyzing the terminal steps in the de novo
      biogenesis of fatty acids is correlated with low survival and high disease
      recurrence in patients with bladder cancer. Pyruvate kinase M2 (PKM2) regulates
      the final step of glycolysis levels and provides a growth advantage to tumors.
      However, it is unclear whether the change of PKM2 has an effect on FASN and what
      is the mechanisms underlying. Here we describe a novel function of PKM2 in
      control of lipid metabolism by mediating transcriptional activation of FASN,
      showing the reduced expression of sterol regulatory element binding protein 1c
      (SREBP-1c). We first discovered that PKM2 physically interacts with the SREBP-1c
      using biochemical approaches, and downregulation of PKM2 reduced the expression
      of SREBP-1c by inactivating the AKT/mTOR signaling pathway, which in turn
      directly suppressed the transcription of major lipogenic genes FASN to reduce
      tumor growths. Furthermore, either PKM2 inhibitor-Shikonin or FASN inhibitor-TVB
      3166 alone induced a strong antiproliferative and anticolony forming effect in
      bladder cancer cell line. The combination of both inhibitors exhibits a super
      synergistic effect on blocking the bladder cancer cells growth. It provides a new
      target and scientific basis for the treatment of bladder cancer.

PMID- 30221355
TI  - Non-destructive classification of apple bruising time based on visible and near
      infrared hyperspectral imaging.
AB  - BACKGROUND: Bruising time of apple is one of the most important factors for
      internal quality assessment. The present study aimed to establish a non
      destructive method for the classification of apple bruising time using visible
      and near-infrared (VNIR) hyperspectral imaging. In this study, VNIR hyperspectral
      images were obtained and analyzed at seven bruising periods. Moreover, regions of
      interest (ROIs) were chosen to construct the bruised region classification model,
      and spectra of bruised regions were collected and resampled based on four
      different methods. Subsequently, machine learning algorithms were employed and
      used for dealing with the time classification model of apples. In order to reduce
      data redundancy and improve the accuracy of the classification model, a tree
      based assembling learning model was used to select feature wavelengths, and
      linear discriminant analysis (LDA) was used to improve the discernibility of
      data. RESULTS: The results revealed that the random forest (RF) model can
      precisely locate bruised regions, while the gradient boosting decision tree
      (GBDT) model can validly classify apple bruising times with 70.59% accuracy. Data
      of 128 wavebands were compressed to 13 wavebands, providing a high accuracy of
      92.86%. CONCLUSION: The results prove that the hyperspectral technique can be
      used for predicting apple bruising time, which will help to assess the internal
      quality and safety of apples. (c) 2018 Society of Chemical Industry.

PMID- 30221357
TI  - ALA-mediated biphasic downregulation of alpha-7nAchR/HIF-1alpha along with
      mitochondrial stress modulation strategy in mammary gland chemoprevention.
AB  - The study elucidates the effect of alpha-linolenic acid (ALA) on mitochondrial
      stress, hypoxic cancer microenvironment, and intervention of cholinergic anti
      inflammatory pathway using N-methyl-N-nitrosourea (MNU) induced estrogen receptor
      (ER+) mammary gland carcinoma and Caenorhabditis elegans model, respectively. The
      efficacy of ALA was scrutinized in vivo and in vitro using various experiments
      like hemodynamic studies, morphological analysis, antioxidants parameters,
      immunoblotting, and quantitative reverse transcription polymerase chain reaction.
      The effect of ALA was also validated using C. elegans worms. ALA administration
      had a positive effect on tissue architecture of the malignancy when scrutinized
      through the whole mount carmine staining, hematoxylin and eosin staining, and
      scanning electron microscopy. The proteomic and genomic checkpoint revealed the
      participation of mitochondrial dysfunction, alteration of hypoxic
      microenvironment, and involvement of cholinergic anti-inflammatory response after
      treatment with ALA. ALA treatment has also increased the level of synaptic
      acetylcholine and acetylcholine esterase with a significant decrease in lipid
      content. It was concluded that ALA persuaded the mitochondrial stress, activation
      of downstream cholinergic anti-inflammatory markers, and favorable regulation of
      hypoxia microenvironment through inhibition of fatty acid synthase and sterol
      regulatory element-binding protein.

PMID- 30221358
TI  - Generic chemoprevention of hepatocellular carcinoma.
AB  - Chronic fibrotic liver disease caused by viral or metabolic etiologies is a high
      risk condition for developing hepatocellular carcinoma (HCC). Even after curative
      treatment of early-stage HCC tumor, the carcinogenic microenvironment persists in
      the remnant diseased liver and supports the development of de novo HCC tumors (de
      novo HCC recurrence). Therefore, prevention of HCC development in patients at
      risk of not only first-primary but also second-primary HCC tumors is
      theoretically the most impactful strategy to improve patient prognosis. However,
      no such therapy has been established to date. One major challenge is the
      identification of clinically relevant targets that can be achieved by utilizing
      the reverse-engineering strategy of chemoprevention discovery, which integrates
      omics information from clinical cohorts with completed follow-up for cancer
      development. Clinical and experimental studies have suggested etiology-specific
      and generic candidate HCC chemoprevention strategies, including statins,
      antidiabetic drugs, selective molecular targeted agents, and dietary and
      nutritional substances. Clinical testing of the candidate compounds can be cost
      effectively performed by combining it with HCC risk biomarker evaluation to
      specify the target patient population most likely to benefit from the therapy.
      Nontoxic, generic agents will have broad clinical applicability across the
      diverse HCC etiologies and clinical contexts and are expected to substantially
      improve the still dismal prognosis of HCC.

PMID- 30221359
TI  - Photosynthetic characteristics of non-foliar organs in main C3 cereals.
AB  - Photosynthesis in non-foliar organs plays an important role in crop growth and
      productivity, and it has received considerable research attention in recent
      years. However, compared with the capability of photosynthetic CO2 fixation in
      leaves, the distinct attributes of photosynthesis in the non-foliar organs of
      wheat (a C3 species) are unclear. This review presents a comprehensive
      examination of the photosynthetic characteristics of non-foliar organs in wheat.
      Compared with leaves, non-foliar organs had a higher capacity to refix respired
      CO2 , higher tolerance to environmental stresses and slower terminal senescence
      after anthesis. Additionally, whether C4 photosynthetic metabolism exists in the
      non-foliar organs of wheat is discussed, as is the advantage of photosynthesis in
      non-foliar organs during times of abiotic stress. Introducing the photosynthesis
      related genes of C4 plants into wheat, which are specifically expressed in non
      foliar organs, can be a promising approach for improving wheat productivity.

PMID- 30221360
TI  - Obesity causes Pgc-1alpha deficiency in the pancreas leading to marked Il-6 up
      regulation via NF-kappaB in acute pancreatitis.
AB  - Obesity is associated with local and systemic complications in acute
      pancreatitis. PPARgamma co-activator 1alpha (PGC-1alpha) is a transcriptional co
      activator and master regulator of mitochondrial biogenesis that exhibits
      dysregulation in obese subjects. Our aims were 1) to study PGC-1alpha levels in
      pancreas from lean or obese rats and mice with acute pancreatitis; and 2) to
      determine the role of PGC-1alpha in the inflammatory response during acute
      pancreatitis elucidating the signaling pathways regulated by PGC-1alpha. Lean and
      obese Zucker rats and lean and obese C57BL6 mice were used first, and
      subsequently wild-type and PGC-1alpha knock-out (KO) mice with cerulein-induced
      pancreatitis were used to assess the inflammatory response and expression of
      target genes. Ppargc1a mRNA and protein levels were markedly down-regulated in
      pancreas of obese mice versus lean mice. PGC-1alpha protein levels increased in
      pancreas of lean mice with acute pancreatitis, but not in obese mice with
      pancreatitis. Il6 mRNA levels were dramatically up-regulated in pancreas of PGC
      1alpha KO mice after cerulein-induced pancreatitis in comparison with wild type
      mice with pancreatitis. Edema and the inflammatory infiltrate were more intense
      in pancreas from PGC-1alpha KO mice than in wild type mice. The lack of PGC
      1alpha markedly enhanced nuclear translocation of phospho-p65 and recruitment of
      p65 to Il6 promoter. PGC-1alpha bound phospho-p65 in pancreas during pancreatitis
      in wild type mice. Glutathione depletion in cerulein-induced pancreatitis was
      more severe in KO mice than in wild type mice. PGC-1alpha KO mice with
      pancreatitis, but not wild type mice, exhibited increased MPO activity in the
      lungs together with alveolar wall thickening and collapse, which were abrogated
      by blockade of the IL-6 receptor gp130 with LMT-28. In conclusion, obese rodents
      exhibit PGC-1alpha deficiency in the pancreas. PGC-1alpha acts as selective
      repressor of NF-kappaB towards IL-6 in pancreas. PGC-1alpha deficiency markedly
      enhanced NF-kappaB-mediated up-regulation of Il6 in pancreas in pancreatitis,
      leading to severe inflammatory response.

PMID- 30221361
TI  - European photopatch test baseline series: A 3-year experience.
AB  - BACKGROUND: In 2012, a consensus was reached regarding a baseline photopatch test
      series on the basis of the results of a European multicentre study. OBJECTIVES:
      To describe experience with the European photopatch test series. METHODS: A
      retrospective analysis of 116 patients tested with the European photopatch test
      series between 2014 and 2016 was performed. RESULTS: Fifty-five positive
      photopatch test reactions in 25 subjects were recorded, most commonly caused by
      the topical non-steroidal anti-inflammatory drugs ketoprofen, dexketoprofen, and
      etofenomate. Organic ultraviolet (UV) absorbers constituted the second main
      category of agents eliciting positive photopatch test reactions. Among UV
      absorbers, benozophenone-3 and octocrylene were the most frequent photoallergens.
      UV absorbers that have been introduced more recently rarely elicited positive
      photopatch test reactions. Positive patch test reactions were less commonly
      observed than positive photopatch test reactions, namely, 21 reactions in 14
      patients. CONCLUSIONS: We present the largest clinical experience with the
      European photopatch test baseline series hitherto reported. The results are
      similar to those underlying the above consensus process, reaffirming the
      usefulness of this series.

PMID- 30221362
TI  - Ploidy-altered phenotype interacts with local environment and may enhance
      polyploid establishment in Knautia serpentinicola (Caprifoliaceae).
AB  - Whole genome duplication is a key process in plant evolution and has direct
      phenotypic consequences. However, it remains unclear whether ploidy-related
      phenotypic changes can significantly alter the fitness of polyploids in nature
      and thus contribute to establishment of new polyploid mutants in diploid
      populations. We addressed this question using a unique natural system
      encompassing a diploid and its sympatric locally established autotetraploid
      derivative. By setting a common garden experiment with two manipulated
      environmental factors (presence/absence of serpentine substrate and competition),
      we tested whether these two locally important factors differently shape the
      phenotypic response of the two ploidy levels. Tetraploids attained significantly
      higher values of both above- and below-ground biomass, and root : shoot ratio
      compared to their diploid progenitors. Tetraploid superiority in vegetative
      fitness indicators was most prominent when they were cultivated together with a
      competitor in nutrient-rich nonserpentine substrate. We show that even
      genetically very closely related diploids and tetraploids can respond differently
      to key environmental factors. Provided there are sufficient nutrients,
      tetraploids can be more successful in tolerating interspecific competition than
      their diploid progenitors. Such superior performance might have provided an
      adaptive advantage for the newly established tetraploid promoting colonisation of
      new (micro-)habitats, which was indeed observed at the natural site.

PMID- 30221363
TI  - Assessing and teaching job-related social skills to adults with autism spectrum
      disorder.
AB  - Few studies have evaluated interventions to improve the job-related social skills
      of adults with autism spectrum disorder. In this study, we examined the efficacy
      of a treatment package for teaching several social skills that are critical to
      job success, such as responding appropriately to feedback and asking for a task
      model from the supervisor. Three adults, aged 19 to 27 years, participated.
      Initial training of each skill consisted of verbal explanations, modeling, and
      role-play with feedback, along with stimulus prompts to promote generalization to
      a different setting. The trainer introduced additional intervention components as
      needed. We also evaluated generalization across different social skills and
      evocative situations. Results indicated that the treatment package was generally
      effective in improving the targeted social skills, and that stimulus prompts may
      be necessary for generalization to a job setting. However, generalized responding
      across social skills rarely emerged. These findings have important implications
      for preparing individuals with autism to function successfully on the job.

PMID- 30221364
TI  - MiR-24-3p regulates cell proliferation and milk protein synthesis of mammary
      epithelial cells through menin in dairy cows.
AB  - MiR-24-3p, a broadly conserved, small, noncoding RNA, is abundantly expressed in
      mammary tissue. However, its regulatory role in this tissue remains poorly
      understood. It was predicted that miR-24-3p targets the 3' untranslated region
      (3'-UTR) of multiple endocrine neoplasia type 1 (MEN1), an important regulatory
      factor in mammary tissue. The objective of this study was to investigate the
      function of miR-24-3p in mammary cells. Using a luciferase assay in mammary
      epithelial cells (MAC-T), miR-24-3p was confirmed to target the 3'-UTR of MEN1.
      Furthermore, miR-24-3p negatively regulated the expression of the MEN1 gene and
      its encoded protein, menin. miR-24-3p enhanced proliferation of MAC-T by
      promoting G1/S phase progression. MiR-24-3p also regulated the expression of key
      factors involved in phosphatidylinositol-3-kinase/protein kinase B/mammalian
      target of rapamycin and Janus kinase/signal transducer and activators of
      transcription signaling pathways, therefore controlling milk protein synthesis in
      epithelial cells. Thus, miR-24-3p appears to act on MAC-T by targeting MEN1. The
      expression of miR-24-3p was controlled by MEN1/menin, indicating a negative
      feedback loop between miR-24-3p and MEN1/menin. The negatively inhibited
      expression pattern of miR-24-3p and MEN1 was active in mammary tissues at
      different lactation stages. The feedback mechanism is a new concept to further
      understand the lactation cycle of mammary glands and can possibly to be
      manipulated to improve milk yield and quality.

PMID- 30221365
TI  - Blood transfusion in sub-Saharan Africa: understanding the missing gap and
      responding to present and future challenges.
AB  - Blood transfusion in sub-Saharan Africa (SSA) is at a crossroad. Significant
      recent developments may help meet local needs in safe blood products and fulfil a
      global health target, as highlighted by the World Health Organization (WHO)
      Millennium and Sustainable Development Goals, in improving supply and safety, and
      ensuring the gradual implementation of selective haemotherapy. When WHO
      recommended the evaluation of convalescent blood or plasma to treat Ebola
      infected patients during the recent epidemics, substantial gaps in local blood
      collection, testing and technology infrastructure and safety, as compared to best
      accepted quality standards, became evident. This evidence should now serve as an
      'electro-shock'/awakening call used to highlight the needs for local governments
      to support National Blood Transfusion Services and establish robust national
      regulatory authorities that are mandated to bear regulatory responsibilities of
      blood establishments. A nationally co-ordinated blood programme is the best tool
      to gather reliable epidemiological data, address local needs in blood and blood
      products and serve public health. A literature review using WHO website and
      PubMed was conducted in this article to outline the current clinical use of blood
      products and plasma derivatives in SSA. This text also intends to highlight the
      gaps to be filled in the coming years with respect to quality, safety, supply and
      efficacy of blood and plasma products, in line with WHO guidelines for
      transfusion.

PMID- 30221366
TI  - Use of an at-home multilevel pregnancy test and an automated call-in system to
      follow-up the outcome of medical abortion.
AB  - OBJECTIVE: To assess the feasibility of using an at-home multilevel pregnancy
      test (MLPT) and interactive voice response (IVR) call-in system for remote follow
      up of medical abortion. METHODS: A prospective pilot study was conducted among
      women who had a medical abortion at up to 70 days at a clinic in Mexico City,
      Mexico, between June 1, 2015, and January 30, 2016. Participants took an MLPT at
      the initial clinic visit and another MLPT at home 2 weeks later. They were
      requested to report their MLPT results via the IVR system and attend the clinic
      for follow-up evaluation. RESULTS: Of 200 women considered for inclusion, 163
      (81.5%) were included in the analysis. Only 10 (6.6%) of the 152 women who had a
      medical abortion on or before 63 days from last menstrual period reported MLPT
      results to the IVR system that required clinical evaluation to assess medical
      abortion outcome. The remaining 142 (93.4%) women in this group reported MLPT
      results that ruled out ongoing pregnancy (confirmed at clinical evaluation).
      Reported MLPT results ruled out ongoing pregnancy among the 11 women who had a
      medical abortion after 63 days; however, 1 (9%) had an ongoing pregnancy at
      clinical evaluation. CONCLUSION: Use of MLPTs and the IVR system provided a
      streamlined approach to follow-up after medical abortion.

PMID- 30221367
TI  - Health-related quality of life experiences in children and adolescents born with
      esophageal atresia: A Swedish-German focus group study.
AB  - BACKGROUND: Esophageal atresia (EA) is a rare malformation of the esophagus,
      which needs surgical treatment. Survival rates have reached 95%, but esophageal
      and respiratory morbidity during childhood is frequent. Child and parent
      perspectives and cultural and age-specific approaches are fundamental in
      understanding children's health-related quality of life (HRQoL) and when
      developing a pediatric HRQoL questionnaire. We aimed to increase the conceptual
      and cross-cultural understanding of condition-specific HRQoL experiences among EA
      children from Sweden and Germany and investigate content validity for an EA
      specific HRQoL questionnaire. METHODS: Eighteen standardized focus groups (FGs)
      with 51 families of EA children aged 2-17 years in Sweden (n = 30 families) and
      Germany (n = 21 families) were used to explore HRQoL experiences, which were
      content analyzed into HRQoL domains. The Swedish HRQoL domains were analyzed
      first and used as framework to evaluate HRQoL content reported in the German FGs.
      HRQoL experiences were then categorized as physical, social, and emotional HRQoL
      burden or resource. RESULTS: One thousand nine hundred eight HRQoL statements
      were recorded. All nine EA-specific HRQoL domains identified in the Swedish FGs
      (eating, social relationships, general life issues, communication, body issues,
      bothersome symptoms, confidence, impact of medical treatment, and additional
      difficulties due to concomitant anomalies) were recognized in the FGs held in
      Germany, and no additional EA-specific HRQoL domain was found. The HRQoL
      dimensions referenced physical burden (n = 655, 34.5%), social burden (n = 497,
      26.0%), social resources (n = 303, 15.9%), emotional burden (n = 210, 11.0%),
      physical resources (n = 158, 8.3%), and emotional resources (n = 85, 4.5%).
      CONCLUSION: This first international FG study to obtain the EA child and his or
      her parents' perspective on HRQoL suggests Swedish-German qualitative
      comparability of the HRQoL domains and content validity for a cross-cultural EA
      specific HRQoL questionnaire. EA children make positive and negative HRQoL
      experiences, but prominently related to physical and social burden, which
      underlines appropriate follow-up care and future research.

PMID- 30221368
TI  - Auxiliary variable-enriched biomarker-stratified design.
AB  - Clinical trials in the era of precision medicine require assessment of biomarkers
      to identify appropriate subgroups of patients for targeted therapy. In a
      biomarker-stratified design (BSD), biomarkers are measured on all patients and
      used as stratification variables. However, such a trial can be both inefficient
      and costly, especially when the prevalence of the subgroup of primary interest is
      low and the cost of assessing the biomarkers is high. Efficiency can be improved
      and costs reduced by using enriched biomarker-stratified designs, in which
      patients of primary interest, typically the biomarker-positive patients, are
      oversampled. We consider a special type of enrichment design, an auxiliary
      variable-enriched design (AEBSD), in which enrichment is based on some
      inexpensive auxiliary variable that is positively correlated with the true
      biomarker. The proposed AEBSD reduces the total cost of the trial compared with a
      standard BSD when the prevalence rate of true biomarker positivity is small and
      the positive predictive value (PPV) of the auxiliary biomarker is larger than the
      prevalence rate. In addition, for an AEBSD, we can immediately randomize the
      patients selected in the screening process without waiting for the result of the
      true biomarker test, reducing the treatment waiting time. We propose an adaptive
      Bayesian method to adjust the assumed PPV while the trial is ongoing. Numerical
      studies and an example illustrate the approach. An R package is available.

PMID- 30221369
TI  - Cause of and countermeasures for oxidation of the cysteine-derived reagent used
      in the amino acid derivative reactivity assay.
AB  - The amino acid derivative reactivity assay (ADRA) is an in chemico alternative to
      animal testing for skin sensitization that solves certain problems found in the
      use of the direct peptide reactivity assay (DPRA). During a recent validation
      study conducted at multiple laboratories as part of the process to include ADRA
      in an existing OECD test guideline, one of the nucleophilic reagents used in ADRA
      N-(2-(1-naphthyl)acetyl)-l-cysteine (NAC)-was found to be susceptible to
      oxidation in much the same manner that the cysteine peptide used in DPRA was.
      Owing to this, we undertook a study to clarify the cause of the promotion of NAC
      oxidation. In general, cysteine and other chemicals that have thiol groups are
      known to oxidize in the presence of even minute quantities of metal ions. When
      metal ions were added to the ADRA reaction solution, Cu2+ promoted NAC oxidation
      significantly. When 0.25 MUm of EDTA was added in the presence of Cu2+ , NAC
      oxidation was suppressed. Based on this, we predicted that the addition of EDTA
      to the NAC stock solution would suppress NAC oxidation. Next, we tested 82
      chemicals used in developing ADRA to determine whether EDTA affects ADRA's
      ability to predict sensitization. The results showed that the addition of EDTA
      has virtually no effect on the reactivity of NAC with a test chemical, yielding
      an accuracy of 87% for predictions of skin sensitization, which was roughly the
      same as ADRA.

PMID- 30221371
TI  - Contemporary Issues in Women's Health.

PMID- 30221372
TI  - Identification of up-regulated transcripts during Pleurotus ostreatus primordium
      stage and characterization of PoALDH1.
AB  - In order to isolate the differentially expressed genes in the primordium stage of
      Pleurotus ostreatus, the SSH cDNA library was constructed using the cDNA from
      dikaryotic mycelium stage as a driver and the cDNA from primordium stage as a
      tester. There were 423 significantly differently expressed clones among 2055
      positive clones after three times of reverse Northern blot differential
      screening. After the repeated sequences being removed, 46 genes were identified
      which were putatively involved in cell rescue and defense, energy metabolism,
      transcription and protein regulation, membrane proteins, and signal transduction;
      18 genes encoding hypothetical proteins with unknown function; 5 genes without
      any homology. PoALDH1 and its full-length cDNA sequence were cloned using the
      Aldehyde dehydrogenase EST isolated from the library. The amino acid sequence of
      PoALDH1 contains conservative glutamic acid and cysteine residues active sites of
      aldehyde dehydrogenase family. When exposed to different concentrations of sodium
      chloride, the mycelium growth was inhibited and the expression level of PoALDH1
      was significantly higher than that of the control one, which indicated that
      PoALDH1 may have the ability to relieve salt stress. The results of this study
      will provide useful information for isolating growth and development related
      genes of P. ostreatus.

PMID- 30221370
TI  - Binocular contrast summation and inhibition depends on spatial frequency,
      eccentricity and binocular disparity.
AB  - PURPOSE: When central vision is compromised, visually-guided behaviour becomes
      dependent on peripheral retina, often at a preferred retinal locus (PRL).
      Previous studies have examined adaptation to central vision loss with monocular
      2D paradigms, whereas in real tasks, patients make binocular eye movements to
      targets of various sizes and depth in 3D environments. METHODS: We therefore
      examined monocular and binocular contrast sensitivity functions with a 26-AFC
      (alternate forced choice) band-pass filtered letter identification task at 2
      degrees  or 6 degrees  eccentricity in observers with simulated central vision
      loss. Binocular stimuli were presented in corresponding or non-corresponding
      stereoscopic retinal locations. Gaze-contingent scotomas (0.5 degrees  radius
      disks of pink noise) were simulated independently in each eye with a 1000 Hz eye
      tracker and 120 Hz dichoptic shutter glasses. RESULTS: Contrast sensitivity was
      higher for binocular than monocular conditions, but only exceeded probability
      summation at low-mid spatial frequencies in corresponding retinal locations. At
      high spatial frequencies or non-corresponding retinal locations, binocular
      contrast sensitivity showed evidence of interocular suppression. CONCLUSIONS:
      These results suggest that binocular vision deficits may be underestimated by
      monocular vision tests and identify a method that can be used to select a PRL
      based on binocular contrast summation.

PMID- 30221373
TI  - Idiopathic granulomatous vulvitis and subsequent oral granulomatosis: a
      diagnostic and therapeutic challenge.

PMID- 30221374
TI  - How many voices did you hear? Natural variability disrupts identity perception
      from unfamiliar voices.
AB  - Our voices sound different depending on the context (laughing vs. talking to a
      child vs. giving a speech), making within-person variability an inherent feature
      of human voices. When perceiving speaker identities, listeners therefore need to
      not only 'tell people apart' (perceiving exemplars from two different speakers as
      separate identities) but also 'tell people together' (perceiving different
      exemplars from the same speaker as a single identity). In the current study, we
      investigated how such natural within-person variability affects voice identity
      perception. Using voices from a popular TV show, listeners, who were either
      familiar or unfamiliar with this show, sorted naturally varying voice clips from
      two speakers into clusters to represent perceived identities. Across three
      independent participant samples, unfamiliar listeners perceived more identities
      than familiar listeners and frequently mistook exemplars from the same speaker to
      be different identities. These findings point towards a selective failure in
      'telling people together'. Our study highlights within-person variability as a
      key feature of voices that has striking effects on (unfamiliar) voice identity
      perception. Our findings not only open up a new line of enquiry in the field of
      voice perception but also call for a re-evaluation of theoretical models to
      account for natural variability during identity perception.

PMID- 30221375
TI  - Massively parallel sequencing of 12 autosomal STRs in Cannabis sativa.
AB  - Massively parallel sequencing (MPS) is an emerging technology in the field of
      forensic genetics that provides distinct advantages compared to capillary
      electrophoresis. This study offers a proof of concept that MPS technologies can
      be applied to genotype autosomal STRs in Cannabis sativa. A custom panel for MPS
      was designed to interrogate 12 cannabis-specific STR loci by sequence rather than
      size. A simple workflow was implemented to integrate the custom PCR multiplex
      into a workflow compatible with the Ion Plus Fragment Library Kit, IonTM Chef,
      and IonTM S5 System. For data sorting and sequence analysis, a custom
      configuration file was designed for STRait Razor v3 to parse and extract STR
      sequence data. This study represents a preliminary investigation of sequence
      variation for 12 autosomal STR loci in 16 cannabis samples. Full concordance was
      observed between the MPS and CE data. Results revealed intra-repeat variation in
      eight loci where the nominal or size-based allele was identical, but variances
      were discovered in the sequence of the flanking region. Although only a small
      number of cannabis samples were evaluated, this study demonstrates that more
      informative STR data can be obtained via MPS.

PMID- 30221376
TI  - Vision and academic performance in primary school children.
AB  - PURPOSE: Vision is considered important for academic performance in children;
      however, the evidence in this area tends to be inconsistent and inconclusive.
      This study explored the association between vision function and visual
      information processing measures and standardised academic achievement scores in
      Grade 3 Australian children. METHODS: Participants included 108 Grade 3 primary
      school children (M = 8.82 +/- 0.32 years) from three state primary schools in
      South-East Queensland. All participants underwent a standard vision screening,
      including distance visual acuity (VA), binocular vision testing and stereoacuity
      (SA). A computer-based battery of visual information processing tests including
      the Development Eye Movement (DEM) test, Visual Sequential Memory (VSM) and
      Symbol Search (SS) was also administered. Australian National Assessment Program
      for Literacy and Numeracy (NAPLAN) scores across five subtests of academic
      performance were obtained for each child: Reading, Writing, Spelling,
      Grammar/Punctuation and Numeracy. RESULTS: The DEM adjusted horizontal and
      vertical times were most strongly associated with all of the NAPLAN subtest
      scores (p < 0.01), adjusted for age and the socio-economic status of the school;
      the DEM ratio was not significantly associated with any of the NAPLAN subtests.
      VSM and SS scores were significantly associated with one or more NAPLAN subtests,
      as were worse and better eye VA; SA showed no significant association with any of
      the NAPLAN subtests. CONCLUSIONS: Performance on the horizontal and vertical DEM
      subtests was most strongly associated with academic performance. These data, in
      conjunction with other clinical data, can provide useful information to
      clinicians regarding their prescribing and management philosophy for children
      with lower levels of uncorrected refractive error and binocular vision anomalies.

PMID- 30221377
TI  - A novel missense mutation of the STS gene in two siblings with X-linked
      ichthyosis, complicated by short stature, bone density reduction, epilepsy, and
      cryptorchidism.

PMID- 30221378
TI  - Acute and long-term outcomes of simultaneous atrioventricular node ablation and
      leadless pacemaker implantation.
AB  - AIMS: Leadless pacemaker (LDP) allows implantation using a femoral approach. This
      access could be utilized for conventional atrioventricular nodal ablation (AVNA).
      It could facilitate unifying the two procedural components. Data regarding its
      feasibility and long-term outcomes remain lacking. We aim to evaluate the
      feasibility and long-term outcomes of sequential LDP and AVNA. METHODS:
      Prospective, observational multicenter study including consecutive patients with
      indication for single-chamber pacemaker placement. In those with additional
      indication for AVNA, ablation was performed immediately after the LPD through the
      same sheath. RESULTS: A total of 137 patients were included. Mean age was 77.9 +/
      10.5 years; 74 (54%) were men. Immediately following LDP implantation, 27
      patients (19.7%) underwent concurrent AVNA. There were six (5.5%) complications
      in patients referred for LDP procedures and three (11%) in those who underwent a
      combined approach. None of these complications were solely attributable to the
      added AVNA component. No mechanical dislodgement, electrical damage to any
      device, or electromagnetic interference ever took place. During a mean follow-up
      period of 123 +/- 48 days, three patients (3.6%) died of noncardiovascular
      causes. The remaining population stayed alive without significant arrhythmias.
      There were no relevant differences with regard to sensing and pacing thresholds
      between patients in the two groups. CONCLUSIONS: AVNA can safely be performed
      immediately following LDP. A combined approach obviates the need for additional
      vascular access and optimizes feasibility and comfort for patients and healthcare
      providers. It offers an acceptable safety and efficacy profile, both acutely and
      upon intermediate-term follow-up.

PMID- 30221379
TI  - Pachydermodactyly: Case report including clinical and histopathologic diagnostic
      pitfalls.
AB  - Pachydermodactyly (PDD) is a rare, benign condition characterized by swelling and
      thickening of the periarticular skin, most commonly at the proximal
      interphalangeal joints. Diagnosis is routinely made through correlation of
      clinical, histopathologic, and radiographic findings. Here, we report a case of
      PDD in a 25-year-old male, with emphasis on the clinical and histopathologic
      differential diagnosis and potential diagnostic pitfalls.

PMID- 30221380
TI  - Preoperative antibiotics and cardiovascular implantable electronic device
      infection: A cohort study in veterans.
AB  - BACKGROUND: Cefazolin is used as standard preoperative prophylaxis for a variety
      of surgical procedures that involve the skin. In contrast, vancomycin is
      recommended for a minority of patients, specifically those with an IgE-mediated
      allergy to beta-lactams and considered in patients with known colonization with
      methicillin-resistant Staphylococcus aureus or at high risk for such. Vancomycin,
      however, has been overprescribed, has nephrotoxicity risk, and may be less
      effective due to its inferior coverage of methicillin-susceptible S. aureus and
      lack of Gram-negative coverage. This study was performed to assess whether
      vancomycin use was associated with an increased incidence of cardiovascular
      implantable electronic device infection (CIEDI) as compared to that of cefazolin
      or other antistaphylococcal beta-lactam antibiotics. METHODS: The VA Informatics
      and Computing Infrastructure database, which included all veterans who underwent
      CIED placement or revision between 2008 and 2015, was used. A logistic regression
      model was constructed to estimate the adjusted odds of CIEDI. RESULTS: Overall,
      10,454 CIED procedures were included, and 98% of them were performed in men with
      a mean age of 71 +/- 12 years. The logistic regression analysis showed that
      vancomycin use alone or in combination with other antibiotics was associated with
      an increased risk of CIEDI (odds ratio 2.99 [1.76-5.06], P-value < 0.001), after
      controlling for other effects. CONCLUSIONS: Our study revealed that among
      patients who received surgical site infection prophylaxis for CIED placement or
      revision, there was: (1) an unanticipated high rate of vancomycin use, and (2) a
      threefold increase in the incidence of subsequent CIEDI among vancomycin
      recipient.

PMID- 30221381
TI  - Long non-coding RNA CCAT1/miR-148a/PKCzeta prevents cell migration of prostate
      cancer by altering macrophage polarization.
AB  - BACKGROUND: Macrophage polarization plays an important role in tumor
      microenvironment, which regulated the prognosis of prostate cancer. However, the
      potential role of it is still need further identification. METHODS: The M1
      Macrophages were inducted using 100 ng/mL LPS and 100 ng/mL IFN-gamma, the M1
      Macrophages were inducted using 20 ng/mL IL-4. TAMs were obtained by culturing
      monocytes for 7 days in RPMI 1640 10% FBS with 50% of conditioned medium from PC
      3 cells real-time PCR was performed to determine the expression of miR-148a,
      CCAT1, and PKCzeta. Western blot was used to measure the level of PKCzeta. The
      cytokine IL-10 was determined using ELISA. Transwell chamber was carried out to
      determine cell migration. Luciferase reporter assay was used to determine the
      relationship between miR-148a and PKCzeta. RESULTS: The expression of miR-148a
      was highest in TAMs, while CCAT1 and PKCzeta were highest in M1 Macrophages.
      Overexpressed miR-148a promoted the level of IL-10 and cell migration. Down
      regulated CCAT1 promoted the level of IL-10 and cell migration, while this
      effects were abolished by co-transfection of si-CCAT1 and miR-148a inhibitor.
      PKCzeta is the target gene of miR-148a. The effects of overexpressed miR-148a on
      the level of IL-10, genes expression, and cell migration were abolished by miR
      148a mimic and pcDNA-PKCzeta. In vivo experiments verified the effects of CCAT1
      and miR-148a on tumor growth. CONCLUSION: CCAT1 knockdown promoted M2 macrophages
      polarization by up-regulating miR-148a, while miR-148a up-regulation promoted M2
      macrophages polarization by down-regulating the expression of PKCzeta.

PMID- 30221382
TI  - Anticoagulation and the risk of complications in ventricular tachycardia and
      premature ventricular complex ablation.
AB  - BACKGROUND: Many patients undergoing ventricular tachycardia (VT) or premature
      ventricular complex (PVC) ablation receive antithrombotic medications.  Their
      uninterrupted use has the potential to affect complication rates. We assessed the
      incidence of complications in a large cohort of patients undergoing these
      procedures, according to antithrombotic medication use. METHODS: From June 2014
      to June 2016, 201 VT and PVC ablations were performed at a single center. We
      allocated patients to three groups: (A) anticoagulation group (international
      normalized ratio >= 1.5 or non-vitamin K anticoagulant or full-dose low-molecular
      weight (LMW) heparin on day of procedure); (B) antithrombotic group (antiplatelet
      therapy and/or prophylactic LMW heparin on day of procedure); and (C) no
      antithrombotics group.  We assessed periprocedural complication rates in each
      group.  Multivariable analysis was performed. RESULTS: Group A (47 patients) had
      8.5% procedural complication rate: one stroke, one pseudoaneurysm, one femoral
      artery occlusion, and one access site hematoma. In this group, 37 patients had
      femoral arterial and 18 had epicardial access. In Group B (46 patients), the
      complication rate was 6.5%: two cardiac tamponades and one pericardial effusion
      without compromise. Group C (108 patients) had a 5.6% complication rate: three
      cardiac tamponades (with one periprocedural death and one concomitant gastric
      vessel injury), one pericardial effusion without compromise, one stomach
      perforation, and two access site hematomas. Multivariable analysis did not show
      any significant predictors of complications, though age approached significance.
      CONCLUSIONS: Complication rates were not significantly different between groups.
      These findings suggest that VT and PVC ablation can be performed safely in
      patients with uninterrupted antithrombotic medications.

PMID- 30221383
TI  - A tetrad apparatus for protein gel casting, electrophoresis, staining, and
      scanning techniques with dual sensors for automatic detection of gel
      polymerization and protein migration.
AB  - Recent advancements in biochemical sciences have facilitated researchers to
      explore the structure and function of macro molecules in a cell. PAGE is one of
      the most favored and adapted laboratory techniques. Due to its simple and
      economical procedures, several variants or new modifications are routinely
      observed in the basic electrophoresis technique that comprises gel casting,
      electrophoresis, staining, and imaging process which consequently necessitates
      additional apparatuses/components in the laboratory. Operation of these
      additional apparatuses/components lengthens the pre- and postelectrophoresis
      procedures involving many intermittent tedious and time-consuming steps. A
      universal apparatus that can facilitate all such associated techniques is lacking
      and is of utmost importance for fast and effective results. An apparatus that can
      perform synchronized action of slab gel casting (16 * 16 cm), electrophoresis
      (SDS-PAGE), dye staining (Coomassie), and imaging (scanning) techniques with real
      time monitoring through sensor technology is described in this article. The
      estimated cost (~$150) of fabrication of the apparatus is very economical and
      simple assembly procedure of the main apparatus can be completed within ~30 min
      after fabrication.

PMID- 30221384
TI  - EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in
      mice with diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is one of the most frequently occurring microvascular
      complications of diabetes. Recent evidence indicates that epidermal growth factor
      receptors (EGFRs) are critical pathogenic players in non-neoplastic diseases,
      including diabetic cardiomyopathy and DR. However, the precise pathogenic
      mechanism of EGFR in DR has yet to be fully understood. In this study, we
      developed a type 1 diabetic early-stage retinopathy mouse model using injections
      of streptozotocin and an oxygen-induced end-stage diabetic retinopathy (OIR)
      model characterized by hypoxia-induced revascularization. We tested the
      hypothesis that the pathogenesis of DR can be reduced by the classic EGFR
      inhibitor, AG1478, in the mouse models. Our data indicated that treatment of
      AG1478 prevented retinal dysfunction, and reduced impairment of retinal
      structures as well as mitochondrial structures in retinal blood vessels in
      diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no
      effects on revascularization at the avascular sites when compared to untreated
      littermates in the OIR model. Our findings provide strong evidence that EGFR
      critically promoted retinal dysfunction, retinal structural impairment, and
      retinal vascular abnormalities in models of DR. We conclude that EGFR can be a
      potential important therapeutic target for treatment of DR.

PMID- 30221385
TI  - When patients' invisible work becomes visible: non-adherence and the routine task
      of pill-taking.
AB  - While the biographical dimensions of chronic illness have been well researched,
      the concrete dimensions of patients' work have not been as thoroughly
      investigated as yet. With the growing concern for self-management, such research
      would be timely. This study aims to better understand patients' invisible work by
      highlighting the causes of unintentional non-adherence as well as strategies for
      adherence. For this purpose, it defines medical treatment adherence as the
      repetition of the pattern of tasks through which a patient succeeds, in a
      technical sense, in taking the right medication at the right time, in the right
      amount, for the right duration. Applying a failure modes and effects analysis
      approach to 48 semi-structured interviews with Dutch patients, it shows the
      negative impact of schedule changes, pressure, positioning changes, lack of
      backup pills and lack of verification tools. Symmetrically, it highlights the
      role of anchoring, sequencing, positioning, cueing, correcting and verifying.
      This result points to the need for an analytical approach of patients' work and
      treatment adherence that would build on the role of routines in organisations and
      in the workplace.

PMID- 30221386
TI  - A hybrid approach for patent ductus arteriosus closure using the Amplatzer Duct
      Occluder.
AB  - OBJECTIVE: We performed closure of the patent ductus arteriosus (PDA) using a
      hybrid approach with an Amplatzer Duct Occluder. METHODS: Six patients (two males
      and four females) underwent PDA closure at a mean age of 7.8 months (range 2-24
      months) and a mean weight of 6.6 kg (range 4.5-13 kg). The main pulmonary artery
      (MPA) was exposed via a minimally invasive left parasternal second intercostal
      space incision. Under transesophageal echocardiography guidance, the PDA occluder
      was implanted via direct puncture of the MPA. RESULTS: The procedure was
      successful in all patients with no residual shunt. There were no hospital deaths,
      and the postoperative course was uneventful. All patients were discharged on the
      3rd to 4th day. There was no residual shunt in any patient on midterm follow-up.
      CONCLUSIONS: The novel hybrid approach is a safe, minimal invasive procedure.
      Further experience and longer follow-up of these patients is necessary to
      conclude whether this technique is applicable to all the patients with a PDA.

PMID- 30221387
TI  - Laboratory evolution and physiological analysis of Saccharomyces cerevisiae
      strains dependent on sucrose uptake via the Phaseolus vulgaris Suf1 transporter.
AB  - Knowledge on the genetic factors important for the efficient expression of plant
      transporters in yeast is still very limited. Phaseolus vulgaris sucrose
      facilitator 1 (PvSuf1), a presumable uniporter, was an essential component in a
      previously published strategy aimed at increasing ATP yield in Saccharomyces
      cerevisiae. However, attempts to construct yeast strains in which sucrose
      metabolism was dependent on PvSUF1 led to slow sucrose uptake. Here, PvSUF1
      dependent S. cerevisiae strains were evolved for faster growth. Of five
      independently evolved strains, two showed an approximately twofold higher
      anaerobic growth rate on sucrose than the parental strain (MU = 0.19 h-1 and MU =
      0.08 h-1 , respectively). All five mutants displayed sucrose-induced proton
      uptake (13-50 MUmol H+ (g biomass)-1  min-1 ). Their ATP yield from sucrose
      dissimilation, as estimated from biomass yields in anaerobic chemostat cultures,
      was the same as that of a congenic strain expressing the native sucrose symporter
      Mal11p. Four out of six observed amino acid substitutions encoded by evolved
      PvSUF1 alleles removed or introduced a cysteine residue and may be involved in
      transporter folding and/or oligomerization. Expression of one of the evolved
      PvSUF1 alleles (PvSUF1I209F C265F G326C ) in an unevolved strain enabled it to
      grow on sucrose at the same rate (0.19 h-1 ) as the corresponding evolved strain.
      This study shows how laboratory evolution may improve sucrose uptake in yeast via
      heterologous plant transporters, highlights the importance of cysteine residues
      for their efficient expression, and warrants reinvestigation of PvSuf1's
      transport mechanism.

PMID- 30221388
TI  - Bipaddle chimaeric forehead flap: A new technique for simultaneous lining and
      cutaneous reconstruction in case of full thickness defects of the nose.
AB  - INTRODUCTION: Many techniques have been described to treat full thickness nasal
      defects. The authors introduce the bipaddle chimaeric forehead flap (BCFF), a new
      alternative technique to achieve simultaneous lining and cutaneous reconstruction
      in case of full thickness hemi-nasal defects, presenting surgical details and
      applications for its clinical use. PATIENTS AND METHODS: From June 2015 to April
      2017, 10 patients presenting with oncological full thickness defects involving
      nasal sidewall and/or nasal ala were reconstructed with the BCFF technique. Mean
      age was 69.4 years. The chimaeric flap was composed of 2 paddles (cutaneous and
      periosteal), nourished by a single supratrochlear pedicle, which were used to
      independently reconstruct the deficient cutaneous and mucosal layers of the nose.
      Cartilage grafts were used in 8/10 patients. RESULTS: Mean surgical time was 114
      minutes. An intermediate thinning operation was performed in 3 out of 10
      patients. All the flaps survived with no partial necrosis or cartilage exposure
      observed. Viability and mucosalization of the periosteal paddle was documented
      both intra-operatively (during the 2nd stage of the operation) and
      postoperatively (with fiberoptic rhinoscopy performed 3 months after the
      procedure). Clinical follow-up period ranged from 4 to 24 months postoperatively.
      The final result was judged sufficient, good and excellent in 1, 5, and 4 cases,
      respectively. CONCLUSIONS: The BCFF technique may be a new alternative approach
      to address full thickness hemi-nasal defects with no extra donor site morbidity,
      allowing primary placement of structural cartilage grafts and immediate
      definition of the nasal subunits to be reconstructed.

PMID- 30221389
TI  - Normal magnetic resonance anatomy of the hind foot of Egyptian buffalo (Bubalus
      bubalis): A correlative low-field T1- and T2-weighted MRI and sectional anatomy
      atlas.
AB  - Buffaloes represent a major source of milk production, especially in developing
      countries including Egypt. The buffalo foot is frequently involved in a large
      proportion of lameness cases. The relatively small size and complexity of its
      structures often render the radiographic evaluation of the foot challenging.
      Magnetic resonance imaging (MRI) is a noninvasive imaging technique that is
      regarded as both safe and accurate for assessment of the foot disorders in both
      man and animals. The purpose of the current investigation was to describe the MRI
      anatomy of buffalo foot using cadaveric hind feet. The feet were subjected to
      consecutive MRI scanning using a 0.3 Tesla scanner. Both T1-weighted (T1-W) and
      T2-weighted (T2-W) spin-echo pulse sequences were applied in dorsal, sagittal and
      transverse planes. The heterogeneity of signal intensities noted amongst foot
      components allowed for clear differentiation of bones, tendons, ligaments,
      adipose tissue and synovial fluid. The T1-W images provided an excellent overview
      of the foot. They were valuable for visualizing the bones and the alignment of
      tendons and ligaments. The T2-W images were particularly useful for the
      evaluation of synovial structures such as tendon sheaths and joint cavities. A
      communication between the two plantar sacs of the metatarsophalangeal (fetlock)
      joints was evident in T2-W images. MRI findings were further confirmed using
      relevant gross anatomical sections. The present study establishes a detailed MRI
      anatomic reference of buffalo foot that could help veterinary researchers,
      clinicians and surgeons for increasing the accuracy of interpretation of foot MRI
      scans of both healthy and diseased animals.

PMID- 30221390
TI  - Indocyanine green retention test in cirrhosis and portal hypertension: Accuracy
      and relation to severity of disease.
AB  - BACKGROUND AND AIMS: Patients with cirrhosis and portal hypertension often
      develop complications relating to hepatic excretory dysfunction. The standard
      measurement of the hepatic excretion is the constant infusion indocyanine green
      clearance (ICGCI ) technique. The ICG 15-min retention test (ICG-r15) is faster,
      more patient friendly, and cheaper. The aims were to compare the ICG-r15 test
      with the standard method, to assess relations to patient characteristics and
      survival, and to assess the ICG-r15 level in healthy control subjects. METHODS:
      This study included 68 patients with cirrhosis and portal hypertension (Child
      class A/B/C:17/37/14). All patients underwent a full liver vein catheterization
      and hemodynamic evaluation with determination of ICG-r15 and ICGCI as the
      reference in a subset of 38 patients. Sixteen healthy control subjects were
      included for compiling a reference interval. RESULTS: The ICG-r15 was increased
      in the cirrhotic patients with increasing values in parallel with liver
      dysfunction (15/41/58%) in Child class A/B/C compared with 7% in the controls (P
      < 0.001). ICG-r15 correlated highly significantly with the ICGCI (r = -0.96, P <
      0.0001) and in a multivariate regression analysis with hepatic venous pressure
      gradient, markers of liver dysfunction and hyperdynamic circulation (P < 0.05
      0.005). In the control group, normal reference values ranged from 0% to 13%. In
      addition, ICG-r15 was significantly related to mortality in the patient group (P
      = 0.02). CONCLUSIONS: Indocyanine green-r15 reflects portal hypertension, the
      degree of hepatic failure, and survival and may replace the standard ICGCI . A
      more elaborated reference interval needs to be compiled, and the prognostic value
      of ICG-r15 should be validated.

PMID- 30221391
TI  - Hb I: A alpha-globin chain variant causing unexpected HbA1c results.
AB  - BACKGROUND: HbA1c is the standard bio-marker for glycemic control in patients
      with diabetes. Here, we report a alpha-globin chain variant and evaluate its
      effect on HbA1c measurements. METHODS: A 21-year-old female was suspected of
      harboring a hemoglobin variant following HbA1c measurement during a routine
      examination using Variant II Turbo 2.0 (Bio-Rad). An oral glucose tolerance test
      was performed using an AU5800 clinical chemistry system (Beckman Coulter). HbA1c
      was reanalyzed using D10 (Bio-Rad), Capillarys 2 Flex Piercing (Sebia), and
      Premier Hb9210 (Trinity Biotech). Hemoglobin analysis was performed using high
      performance liquid chromatography (HPLC) on the Bio-Rad Variant II (beta
      thalassemia short program) and capillary electrophoresis (CE, Capillarys 2 Flex
      Piercing, Hb program). Sanger sequencing of alpha and beta genes was also
      conducted. RESULTS: HbA1c was initially measured at 24.2% using Variant II Turbo
      2.0. For the oral glucose tolerance test, fasting glucose, 1-hour, and 2-hour
      levels were recorded as 4.25, 7.89, and 5.34 mmol/L, respectively. Subsequently,
      HbA1c values determined by D10, Capillarys 2 Flex Piercing (HbA1c program), and
      Premier Hb9210 were 4.5% (26 mmol/mol), no HbA1c value, and 4.8 (29 mmol/mol),
      respectively. Hemoglobin analyzed using CE and HPLC revealed an abnormal
      hemoglobin. Sanger sequencing identified a transversion mutation of the alpha2
      gene [CD16(AAG>GAG), Lys>Glu, HBA2: c.49 A>G], corresponding to a Hb I variant.
      CONCLUSION: An unusually high HbA1c or discordance between blood sugar and HbA1c
      values should alert about the possibilities of hemoglobin variants.

PMID- 30221392
TI  - Gene mutation and pedigree analysis of tetrahydrobiopterin deficiency in a Uygur
      family of China.
AB  - BACKGROUND: Tetrahydrobiopterin (BH4 ) deficiency is an autosomal recessive
      disorder, which is caused by an enzyme deficiency involved in its synthetic or
      metabolic pathways. Clinical symptoms may include microcephaly, hypoevolutism,
      severe ataxia, and seizures. The purposes of this study are to analyze the
      genotype-phenotype and the pedigree of the first case of BH4 deficiency in the
      Uygur of China. METHODS: (a) This patient received tandem mass spectrometry,
      urinary neopterin and biopterin analysis, and determination of dihydropteridine
      reductase (DHPR) activity in dried blood spots. (b) Blood DNA samples of this
      patient and her three family members were collected for gene sequencing and
      mutation analysis. RESULTS: (a) The basic urinary neopterin and biopterin were
      1.07 mmol/mol Cr and 3.12 mmol/mol Cr, respectively, and biopterin percentage was
      74.42%. The DHPR activity of this patient was 31.11% of normal control. (b)
      Sanger sequencing of PAH gene in this patient was negative but positive of her
      sister, which carries 2 heterozygous mutation c.781C>T and c.1238G>C. Next
      generation sequencing on the patient identified a homozygous mutation in the
      quinoid dihydropteridine reductase (QDPR) gene at c.508G>A, which was confirmed
      by Sanger sequencing. CONCLUSION: (a) The patient was the first case of clinical
      diagnosis of BH4 deficiency in the Uighur. And there are two types of
      hyperphenylalaninemia (HPA) in the same family. (b) The mild HPA patient with
      severe nervous system damage should pay more attention to the BH4 deficiency. (c)
      Using next-generation sequencing technology can increase the mutation detection
      rate when the hereditary diseases are highly suspected in clinic.

PMID- 30221393
TI  - Surgical repair of a left main coronary artery aneurysm.
AB  - We report the repair of a 6.5 * 5.3-cm left main coronary artery aneurysm by
      marsupialization of the aneurysm sac and coronary artery bypass grafting.

PMID- 30221394
TI  - Toll-like receptors signaling network in pre-eclampsia: An updated review.
AB  - Toll-like receptors (TLRs) are innate immune cells receptors. They are expressed
      on leukocytes, epithelial cells, and more particularly on placental immune cells
      and chorion trophoblast. Upregulation of innate immune response occurs during
      normal pregnancy, but its excessive activity is involved in the pathology of
      pregnancy complications including pregnancy-induced hypertension and pre
      eclampsia (PE). The recent studies about the overmuch inflammatory responses and
      aberrant placentation are associated with increased expression of TLRs in PE
      patients. This review has tried to focus on the relationship between some
      activities of TLRs and the risk of preeclampsia development.

PMID- 30221395
TI  - Genetic association analysis with pedigrees: Direct inference using the composite
      likelihood ratio.
AB  - The likelihood function represents statistical evidence given data and a model.
      The evidential paradigm (EP), an alternative to Bayesian and Frequentist
      paradigms, provides considerable theory demonstrating evidence strength for
      different parameter values via the ratio of likelihoods at different parameter
      values; thus, enabling inference directly from the likelihood function. The
      likelihood function, however, can be difficult to compute; for example, in
      genetic association studies with a binary outcome in large pedigrees. Composite
      likelihood (CL) is an alternative when the real likelihood is intractable. We
      show CLs have the two large sample properties of the EP for reliable evidence
      interpretation: (1) CL supports the true value over a false value by an
      arbitrarily large factor; and (2) the probability of favouring a false value over
      the true value is small and bounded. Using simulation, and in a genetic
      association analysis of reading disability (RD) in large rolandic epilepsy
      pedigrees, we show that the CL approach yields valid statistical inference and
      identifies RD associated variants. When compared to analyses using generalized
      estimating equations, results show a similar prioritization of SNPs, although the
      CL approach provides additional complementary information, and more intuitive
      solutions to the multiple hypothesis testing problem.

PMID- 30221397
TI  - Biotin interference in TSH, FT4, and FT3 assays based on the LOCI technology:
      Identifying interference by dilution.
AB  - BACKGROUND: Although biotin interferences in TSH, FT3, FT4, and other
      biotinylated antibody-based assays manufactured by Roche Diagnostics have been
      well studied, there are relatively few reports on biotin interference in biotin
      based assays manufactured by other companies. We investigated biotin
      interferences in TSH, FT4, and FT3 assays based on the LOCI (luminescent oxygen
      channeling assay) technology using the Dimension Vista 1500 analyzer (Siemens).
      METHODS: We prepared four serum pools using leftover specimens. Three serum pools
      were prepared initially for the original study but the 4th pool was prepared
      three months later. The aliquots of serum pool one and two were supplemented with
      various amounts of biotin (50 -1200 ng/mL) followed by determination of TSH, FT4,
      and FT3 concentrations. The aliquots of third pool were also supplemented with
      biotin to investigate whether 1:3 dilution could identify biotin interference.
      Aliquots of serum pool four were supplemented with biotin in order to study
      reproducibility of our original data. RESULTS: We observed significantly elevated
      FT3 levels at biotin concentration of 100 ng/mL. In contrast, FT4 levels were
      falsely elevated but TSH levels were falsely decreased at a biotin level of 500
      ng/mL. We also observed nonlinearity in dilution experiment. CONCLUSIONS: We
      conclude that FT3 assay is most susceptible to biotin interference (threshold:
      100 ng/mL) while the FT4 and TSH assays are less affected (threshold: 500 ng/mL).
      In addition, we also observed nonlinearity upon 1:3 dilution, which may indicate
      biotin interference (or interference from other compounds).

PMID- 30221396
TI  - Copy number variations in the GATA4, NKX2-5, TBX5, BMP4 CRELD1, and 22q11.2 gene
      regions in Chinese children with sporadic congenital heart disease.
AB  - BACKGROUND: Congenital heart disease (CHD) is a common birth defect originating
      from both environmental and genetic factors. An overabundance of copy number
      variations (CNVs) affecting cardiac-related genes has previously been detected in
      individuals with CHD. OBJECTIVE: To evaluate if the presence of CNVs in the
      22q11.2 region, and to determine whether GATA4, NKX2-5, TBX5, BMP, and CRELD1
      genes contributed toward the pathogenesis of isolated incidences of CHDs in
      southwest China. METHODS: In total 167 patients from southwest China with
      sporadic CHD were studied, including 121 patients with ventricular septal defect
      (VSD), 24 with atrial septal defect (ASD), 12 with tetralogy of fallot (TOF), six
      VSD cases with TOF, two cases with patent ductus arteriosus (PDA), and two VSD
      cases with ASD. 22q11.2, GATA4, NKX2-5, TBX5, BMP4, and CRELD1 regions were
      screened using MLPA and copy number variation sequencing (CNV-Seq). RESULTS: A
      2.5-2.8 Mb deletion in the 22q11.2 region was identified in 5 patients with CHD.
      Two of these patients were diagnosed with VSD, while two had VSD and ASD, and the
      other had TOF. 5 patients correspond to the same classical DiGeorge syndrome. A
      0.86 Mb duplication in the 22q11.2 region was identified in a PDA patient, whom
      was without extracardiac symptoms. CONCLUSION: These data suggest that copy
      number variation in the 22q11.2 region is common in CHD patients in southwest
      China. Regardless of the presence or absence of extracardiac symptoms, results
      also indicate that it is necessary to perform prenatal screening for CHD.

PMID- 30221398
TI  - How to develop IL-17-producing gammadelta T cells.

PMID- 30221399
TI  - LPS expands MDSCs by inhibiting apoptosis through the regulation of the GATA2/let
      7e axis.
AB  - Myeloid-derived suppressor cells (MDSCs) represent a group of immature myeloid
      cells composed of myeloid progenitor cells and immature myeloid cells that can
      negatively regulate immune responses by inhibiting T-cell function. In mice,
      MDSCs are broadly defined by the expression of CD11b and Gr1. We and others have
      shown that injection of a lethal or sublethal dose of lipopolysaccharide (LPS)
      into mice could result in the expansion of MDSCs in the bone marrow (BM), spleen
      and blood. Until now, the molecular mechanisms responsible for this expansion are
      poorly studied; specifically, the roles of the individual microRNAs (miRNAs)
      which may be involved remain largely unknown. We performed microarray analysis to
      compare the miRNA expression profiles of CD11b+ Gr1+ cells sorted from the BM of
      LPS-injected and phosphate-buffered saline-injected mice. We identified let-7e,
      which was highly upregulated in the LPS-treated group, as a potent regulator of
      LPS-induced MDSC expansion. Furthermore, let-7e overexpression in BM chimeric
      mice led to a noticeable increase in the population of CD11b+ Gr1+ cells, which
      resulted from reduced cellular apoptosis. Further studies showed that let-7e
      could directly target caspase-3 to inhibit cell apoptosis, and upregulation of
      let-7e in LPS-stimulated MDSCs could be due to the relieved repression of let-7e
      transcription exerted by downregulated GATA2. Our findings suggest that LPS
      expands MDSCs by inhibiting apoptosis through the regulation of the GATA2/let-7e
      axis.

PMID- 30221400
TI  - Role of probe-based confocal laser endomicroscopy-targeted biopsy in the
      molecular and histopathological study of gastric cancer.
AB  - BACKGROUND AND AIM: A high yield of biopsy is mandatory to perform molecular
      genetic research with endoscopically obtained gastric cancer tissues. We
      evaluated whether probe-based confocal laser endomicroscopy (pCLE) can increase
      the yield of endoscopic biopsy for gastric cancer compared with white light
      endoscopy (WLE). METHODS: All lesions in the pCLE and WLE groups were initially
      evaluated through WLE. In the pCLE group, lesions were further examined through
      pCLE. In the pilot study, five and three biopsy specimens were obtained for
      histopathological examination and tumor marker analysis, respectively. In the
      confirmatory study, six biopsy specimens for histopathological evaluation were
      obtained. RESULTS: A total of 30 gastric cancers and 61 undifferentiated-type
      gastric cancers were analyzed in the pilot and confirmatory studies,
      respectively. The proportion of cancer cells in biopsy samples of poorly
      differentiated adenocarcinoma or signet ring cell carcinoma was higher in the
      pCLE group than in the WLE group in both the pilot and confirmatory studies
      (pilot: median proportion, 65% vs 30%, P = 0.010; confirmatory: mean +/- standard
      deviation, 49.5 +/- 29.3 vs 29.3 +/- 13.7, P = 0.002). The expression ratio of
      tumor markers including carcinoembryonic antigen, GW112, HOX transcript antisense
      RNA, and H19 tended to be higher in the pCLE group than in the WLE group.
      CONCLUSION: Probe-based confocal laser endomicroscopy-targeted biopsy provided
      superior results in terms of the proportion of cancer cells in biopsy samples
      compared with WLE-targeted biopsy in gastric cancer with undifferentiated
      histology.

PMID- 30221401
TI  - Optimization of 13 C-urea breath test threshold levels for the detection of
      Helicobacter pylori infection in a national referral laboratory.
AB  - BACKGROUND: Threshold values for 13 C-urea breath test (13C-UBT) positivity may
      be affected by various sociodemographic, host, bacterial, and laboratory factors.
      Manufacturer recommended cutoffs for 13C-UBT assays may not be applicable in all
      settings. Optimizing 13C-UBT cutoffs may have profound public health
      ramifications. We aimed to determine the optimal threshold for 13C-UBT positivity
      in our population. METHODS: Consecutive test samples collected at our central
      laboratory from patients undergoing a first-time 13C-UBT between 1 January 2010
      and 31 December 2015 were included. The difference between values at 30 minutes
      and at baseline (T30-T0) was expressed as delta over baseline (DOB). Cluster
      analysis was performed on the 13C-UBT test results to determine the optimal
      cutoff point with minimal interclass variance. RESULTS: Two lakhs thirty four
      thousand eight hundred thirty one patients (87 291 (37.2%) male, age 39.9 +/-
      19.9) underwent a first-time 13C-UBT, including 124 701 (53.1%) negative and 110
      130 (46.9%) positive tests, using the manufacturer-recommended cutoff of 3.5 DOB.
      Cluster analysis determined an optimized cutoff of 2.74 DOB, representing an
      additional 2180 (0.93%) positive subjects who had been previously categorized as
      negative according to the manufacturer-specified cutoff of 3.5 DOB. Mean positive
      and negative DOB values were 19.54 +/- 14.95 and 0.66 +/- 0.51, respectively. The
      cutoffs for male and female subjects were 2.23 and 3.05 DOB, respectively.
      Threshold values for <45-year-olds, 45-60-year-olds and >60-year-olds were 2.67,
      2.55, and 2.93 DOB, respectively. Of the 2180 (0.93%) patients with DOB 2.73
      3.49, 289 (13.3%) performed a subsequent 13C-UBT and 140 (48.4%) remained
      positive when tested at 20.3 +/- 14.4 months. CONCLUSIONS: Major referral
      laboratories should optimize threshold values for 13C-UBT positivity for their
      geographical location. Different cutoff values should be applied for male and
      female subjects.

PMID- 30221402
TI  - Laboratory diagnosis for thalassemia intermedia: Are we there yet?
AB  - BACKGROUND: Differentiation between thalassemia major and thalassemia intermedia
      at presentation is not uniformly characterized, for which an absolute criteria
      needs to be developed. This study investigated the primary and secondary genetic
      modifiers to develop a laboratory finding by forming different genetic mutational
      combinations seen among thalassemia intermedia patients and comparing them with
      thalassemia major. METHODS: This cross-sectional study analyzed 315 thalassemia
      intermedia patients. One hundred and five thalassemia major patients were
      recruited on the basis of documented evidence of diagnosis and were receiving
      blood transfusion therapy regularly. Various mutational combinations were
      identified, and comparison was performed between thalassemia intermedia and major
      using statistical software STATA 11.1. RESULTS: The mean age of the total
      population was 5.9 +/- 5.32 years of which 165 (52%) were males. Of the two
      groups (thalassemia intermedia and thalassemia major), IVSI-5, IVSI-1, and Fr 8-9
      were more prevalent among the thalassemia intermedia cohort. When comparison was
      performed between the thalassemia intermedia and thalassemia major patients, it
      showed significant results for the presence of Xmn-1 polymorphism. CONCLUSION:
      The presence of IVSI-5 homozygous with Xmn-1, IVSI-5 heterozygous with Xmn-1, Cd
      30 homozygous with or without Xmn-1 and IVSI-1 homozygous or heterozygous either
      with or without Xmn-1 prove to be strong indicators towards diagnosis of
      thalassemia intermedia.

PMID- 30221403
TI  - Dynamic clinical prediction models for discrete time-to-event data with competing
      risks-A case study on the OUTCOMEREA database.
AB  - The development of clinical prediction models requires the selection of suitable
      predictor variables. Techniques to perform objective Bayesian variable selection
      in the linear model are well developed and have been extended to the generalized
      linear model setting as well as to the Cox proportional hazards model. Here, we
      consider discrete time-to-event data with competing risks and propose methodology
      to develop a clinical prediction model for the daily risk of acquiring a
      ventilator-associated pneumonia (VAP) attributed to P. aeruginosa (PA) in
      intensive care units. The competing events for a PA VAP are extubation, death,
      and VAP due to other bacteria. Baseline variables are potentially important to
      predict the outcome at the start of ventilation, but may lose some of their
      predictive power after a certain time. Therefore, we use a landmark approach for
      dynamic Bayesian variable selection where the set of relevant predictors depends
      on the time already spent at risk. We finally determine the direct impact of a
      variable on each competing event through cause-specific variable selection.

PMID- 30221404
TI  - Recent Progress of Hybrid Solid-State Electrolytes for Lithium Batteries.
AB  - Conventional liquid electrolytes for lithium batteries usually suffer from
      irreversible decomposition and safety concerns. Solid state electrolytes (SSEs)
      have been considered as the key for advanced lithium batteries with improved
      energy density and safety, whereas challenges remain for polymer and inorganic
      SSEs. Recently, hybrid solid-state electrolytes (HSSEs) that integrate the merits
      of different electrolyte systems have been under intensive study. Herein, we
      summarize the recent progress of HSSEs with different compositions and
      structures. The design principle of each type of HSSEs are discussed, as well as
      their ionic conducting mechanism, electrochemical performance and effects of
      compositional/structural control. Finally, challenges and perspectives are
      provided for the future development of HSSEs and solid-state lithium batteries.

PMID- 30221405
TI  - Low-Temperature Cross-Linkable Small Molecules for Fully Solution-Processed
      OLEDs.
AB  - Cross-linkable hole-transporting, host, and electron-transporting materials with
      a new cross-linking group, uracil, are designed and synthesized. These compounds
      exhibited good solubility in common organic solvents and excellent solvent
      resistance after cross-linking at a low temperature of 120  degrees C. The OLED
      was fabricated by all-solution processing using cross-linkable synthetic
      compounds, except for the electrodes. This device exhibited a current efficiency
      of 39.2 cd A-1 and a power efficiency of 15.3 lm W-1 .

PMID- 30221406
TI  - Directional Self-Assembly and Photoinduced Polymerization of Diacetylene
      Containing Platinum(II) Terpyridine Complexes.
AB  - A series of newly designed and synthesized diacetylene-containing platinum(II)
      terpyridine complexes exhibited intriguing self-assembly properties. Facilitated
      by Pt???Pt, pi-pi stacking, hydrogen-bonding and hydrophobic-hydrophobic
      interactions, these complexes are preorganized to readily undergo topochemical
      polymerization reactions upon photoirradiation. The in situ polymerization of the
      diacetylene units to form polydiacetylene, indicated by the UV/Vis spectral
      changes, gel permeation chromatography and dynamic light scattering, was found to
      alter their assembly behaviours, as revealed by TEM images.

PMID- 30221407
TI  - Xenotransplantation literature update, July/August 2018.

PMID- 30221408
TI  - Observations below multiple lower limits of quantification: How to estimate the
      mean and variance.
AB  - Multiple lower limits of quantification (MLOQs) result if various laboratories
      are involved in the analysis of concentration data and some observations are too
      low to be quantified. For normally distributed data under MLOQs there exists only
      the multiple regression method of Helsel to estimate the mean and variance. We
      propose a simple imputation method and two new maximum likelihood estimation
      methods: the multiple truncated sample method and the multiple censored sample
      method. A simulation study is conducted to compare the performances of the newly
      introduced methods to Helsel's via the criteria root mean squared error (RMSE)
      and bias of the parameter estimates. Two and four lower limits of quantification
      (LLOQs), various amounts of unquantifiable observations and two sample sizes are
      studied. Furthermore, the robustness is investigated under model
      misspecification. The methods perform with decreasing accuracy for increasing
      rates of unquantified observations. Increasing sample sizes lead to smaller bias.
      There is almost no change in the performance between two and four LLOQs. The
      magnitude of the variance impairs the performance of all methods. For a smaller
      variance, the multiple censored sample method leads to superior estimates
      regarding the RMSE and bias, whereas Helsel's method is superior regarding the
      bias for a larger variance. Under model misspecification, Helsel's method was
      inferior to the other methods. Estimating the mean, the multiple censored sample
      method performed better, whereas the multiple truncated sample method performs
      best in estimating the variance. Summarizing, for a large sample size and
      normally distributed data we recommend to use Helsel's method. Otherwise, the
      multiple censored sample method should be used to obtain estimates of the mean
      and variance of data including MLOQs.

PMID- 30221409
TI  - Bifunctional Molecular Probes for Activity-Based Visualization of Quinone
      Dependent Amine Oxidases.
AB  - The design, synthesis, and evaluation of two bifunctional molecular probes that
      can be used to visualize quinone-dependent amine oxidase enzymes in an activity
      dependent manner are described. These probes use alkylhydrazines to irreversibly
      bind the target enzymes, which can then be visualized with either Western
      blotting or in-gel fluorescence. The results show that the Western blotting
      readout, which utilizes commercially available anti-nitrophenyl antibodies to
      detect a simple dinitrophenyl antigen, provides a stronger readout than the
      fluorescein-based fluorescence readout. This visualization strategy can be used
      to measure the potency of enzyme inhibitors by selectively visualizing the active
      enzyme that remains after treatment with an inhibitor. Looking forward, this
      probe molecule and visualization strategy will enable activity-based protein
      profiling experiments, such as determining inhibitor selectivity values within
      full proteome mixtures, for this family of amine oxidase enzymes.

PMID- 30221410
TI  - Determination of silyl peroxides by ultra-performance liquid
      chromatography/electrospray ionisation mass spectrometry.
AB  - RATIONALE: Residual initiators in polymers are a concern in the case of products
      that come directly into contact with the human body or food. Due to low
      concentrations and difficulties in the sample preparation, highly sensitive and
      selective methods are required. METHODS: A series of bis-silyl- and alkyl-silyl
      peroxides were analysed by electrospray ionisation mass spectrometry (ESI-MS) on
      an ultra-performance liquid chromatography/time-of-flight (UPLC/TOF) instrument.
      Li, Na, K, and NH4 acetates were used to promote the formation of [M + Me]+ ions.
      The sample preparation involved only dissolution of the polymer sample in 0.1 mL
      of acetonitrile, followed by precipitation with 1 mL of water. A portion of 0.1-1
      MUL of the solution was then analysed without further treatment by UPLC/ESI-MS.
      RESULTS: Limits of detection (LODs) were in the range of 0.06-9 pmol, depending
      on the peroxide structure. On average, the signal intensity increased with the
      number of phenyl groups in a peroxide and decreased in the order Na > Li > K >
      NH4 . Peroxides that did not contain phenyl groups could not be detected.
      Collision-induced dissociation experiments can be used for structural
      investigations of alkyl-silyl peroxides. It was possible to detect 2 * 10-4 %
      (LOD = 7 * 10-5 %) of unreacted Ph3 SiOOt-Bu in the poly(methyl methacrylate)
      sample. CONCLUSIONS: The method is suitable for the analysis of trace peroxide
      initiators in polymers and for other purposes where LODs in the pmol range are
      required.

PMID- 30221411
TI  - The interplay between chemical speciation and physiology determines the
      bioaccumulation and toxicity of Cu(II) and Cd(II) to Caenorhabditis elegans.
AB  - Using the well-documented model organism Caenorhabditis elegans, a combined
      analysis of metal speciation in the exposure medium and body burdens of metals
      (Zn, Cu and Cd) was performed, and factors that are predictive of toxicological
      endpoints in single metal and mixed metal exposures were identified. Cu, and to a
      lesser extent Cd, is found to associate with Escherichia coli in the exposure
      medium (the food source for C. elegans) as evidenced by the observed decrease in
      both their dissolved and free metal ion concentrations. Together with a critical
      analysis of literature data, our results suggest that free metal ion
      concentrations and thus aqueous uptake routes are the best predictor of internal
      concentrations under all conditions considered, and of metal toxicity in single
      metal exposures. Additional factors are involved in determining the toxicity of
      metal mixtures. In general, the eventual adverse effects of metals on biota are
      expected to be a consequence of the interplay between chemical speciation in the
      exposure medium, timescale of exposure, exposure route as well as the nature and
      timescale of the biotic handling pathways.

PMID- 30221412
TI  - Preliminary assessment of stable nitrogen and oxygen isotopic composition of
      USGS51 and USGS52 nitrous oxide reference gases and perspectives on calibration
      needs.

PMID- 30221413
TI  - Carbon-Based Photocathode Materials for Solar Hydrogen Production.
AB  - Hydrogen is considered a promising environmentally friendly energy carrier for
      replacing traditional fossil fuels. In this context, photoelectrochemical cells
      effectively convert solar energy directly to H2 fuel by water photoelectrolysis,
      thereby monolitically combining the functions of both light harvesting and
      electrolysis. In such devices, photocathodes and photoanodes carry out the
      hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER),
      respectively. Here, the focus is on photocathodes for HER, traditionally based on
      metal oxides, III-V group and II-VI group semiconductors, silicon, and copper
      based chalcogenides as photoactive material. Recently, carbon-based materials
      have emerged as reliable alternatives to the aforementioned materials. A
      perspective on carbon-based photocathodes is provided here, critically analyzing
      recent research progress and outlining the major guidelines for the development
      of efficient and stable photocathode architectures. In particular, the functional
      role of charge-selective and protective layers, which enhance both the efficiency
      and the durability of the photocathodes, is discussed. An in-depth evaluation of
      the state-of-the-art fabrication of photocathodes through scalable, high
      troughput, cost-effective methods is presented. The major aspects on the
      development of light-trapping nanostructured architectures are also addressed.
      Finally, the key challenges on future research directions in terms of potential
      performance and manufacturability of photocathodes are analyzed.

PMID- 30221414
TI  - U-score system for predicting time to recurrence after urethral reconstruction in
      patients with anterior urethral stricture.

PMID- 30221415
TI  - Isolation and Crystallographic Characterization of Lu3 N@C2n (2n=80-88): Cage
      Selection by Cluster Size.
AB  - The small Sc3 N cluster has only been found in such small cages as C2n (2n=68,
      78, 80, 82), whereas the large M3 N (M=Y, Gd, Tb, Tm) clusters choose those
      larger cages C2n (2n=82-88). Herein, concrete experimental evidence is presented
      to establish the size effect of the internal metallic cluster on selecting the
      outer cage of endohedral metallofullerenes (EMFs) by using a medium-sized metal,
      lutetium, which possesses an ionic radius between Sc and Gd. A series of lutetium
      containing EMFs have been obtained and their structures are unambiguously
      determined as Lu3 N@Ih (7)-C80 , Lu3 N@D5h (6)-C80 , Lu3 N@C2v (9)-C82 , Lu3 N@Cs
      (51365)-C84 , Lu3 N@D3 (17)-C86 , and Lu3 N@D2 (35)-C88 by single-crystal X-ray
      diffraction crystallography. It was confirmed that the encaged Lu3 N cluster
      always adopts a planar geometry in Lu3 N@C80-88 isomers to ensure substantial
      metal-cage/metal-nitrogen interactions. As a result, the Lu3 N cluster selects
      the C2v (9)-C82 cage, which also encapsulates Sc3 N, instead of the Cs (39663)
      C82 cage which is more suitable for M3 N (M=Y, Gd, Tb, Tm). However, different
      from Sc3 N, Lu3 N can also template the C84-88 cages which are absent for Sc3 N
      containing EMFs, confirming clearly the size effect of the internal cluster on
      selecting the outer cage.

PMID- 30221416
TI  - Reflex urine culture testing in an ambulatory urology clinic: Implications for
      antibiotic stewardship in urology.
AB  - OBJECTIVES: To evaluate the performance characteristics of urinalysis and urine
      microscopy parameters for predicting urine culture results and to implement a
      reflex urine culture program. METHODS: We reviewed the charts of all patients
      presenting to our clinic January-March 2013 and June-August 2014, excluding those
      who were catheter-dependent or with urinary diversions. We assessed the
      association of urinalysis and urine microscopy parameters on urine culture
      outcomes defining a positive urinalysis as nitrite-positive and/or the presence
      of >=5 white blood cells per high-powered field with bacteria and a positive
      urine culture as >=10 000 colony-forming units/mL excluding diphtheroids. We
      carried out logistic regression to assess for predictors of positive urine
      culture to inform implementation of a reflex urine culture program. RESULTS: A
      total of 2764 patients were evaluated. Logistic regression using urinalysis
      variables identified positive nitrites (odds ratio 18.6, P < 0.001) and large
      leukocyte esterase (odds ratio 41.8, P < 0.001) as the strongest predictors of
      positive urine culture. Logistic regression using urine microscopy variables
      identified >50 white blood cells per high-powered field (odds ratio 13.6, P <
      0.001) and moderate/many bacteria (odds ratio 16.8, P < 0.001) as the strongest
      predictors of positive urine culture. We used our positive urinalysis definition
      to implement the reflex urine culture program and noted a 60% reduction in urine
      culture rates over the first 3 months of implementation. CONCLUSIONS: A urine
      positive for nitrites and/or >=50 white blood cells per high powered field with
      bacteria seems to have a strong association with a positive urine culture and the
      best negative predictive value. A reflex urine culture program is an effective
      strategy to decrease the rates of unnecessary urine culture and their associated
      costs.

PMID- 30221417
TI  - Soluble nondigestible carbohydrates improve intestinal function and increase
      caecal coliform load in broiler chickens.
AB  - Diets rich in various soluble nondigestible carbohydrates (sNDCs) were evaluated
      on different intestinal characteristics (histological, physico-chemical and
      microbiological) of chickens and compared with a maize-based diet as a control. A
      total of 160 Ross 308 male chickens were kept in deep litter pens (n = 40) and
      fed their appropriate diets from Day 1 to Day 35 of life. Four isocaloric and
      isonitrogenous diets, differing in their sNDC content, were composed; control
      (containing maize as the only cereal), maize-wheat-based (M + W) and maize-based
      supplemented with either 20 g/kg inulin (M + I) or 30 g/kg lactose (M + L). All
      of the diets tested decreased ileal crypt depth, ileal muscle layer thickness and
      increased caecal coliform counts relative to the control group. Villus-crypt
      ratio increased only in the M + L group. Ileal digesta of chickens fed the M + W
      diet had the highest ileal viscosity and the highest caecal butyrate, valerate
      and total short-chain fatty acid concentrations while the lowest pH was observed
      in caecal contents of chickens fed the M + I diet. The diet had no effect on
      ileal or caecal goblet cell and intraepithelial lymphocyte numbers. Lactobacillus
      counts in the caecal content remained unchanged. According to the present study,
      various sNDC sources may have beneficial gut health effects, however, some of the
      intestinal variables are dependent on the type of sNDCs.

PMID- 30221419
TI  - 5-hydroxytryptophan attenuates imiquimod-induced psoriasiform dermatitis probably
      through inhibition of IL-17A production and keratinocyte activation.
AB  - Psoriasis is a chronic autoimmune disease with keratinocyte activation and
      lymphocyte infiltration in the skin. Our previous study found that 5
      hydroxytryptophan (5(OH)Trp), a tryptophan metabolite, alleviated collagen
      induced arthritis and suppressed cytokine production. In this study, we evaluated
      the effects of 5(OH)Trp in a mouse model for psoriasiform dermatitis, induced by
      imiquimod (IMQ). We showed that 5(OH)Trp significantly reduced the cumulative
      scores, epidermal thickness and ki-67 expression in the skin. In addition,
      5(OH)Trp decreased local and systemic inflammation. Moreover, 5(OH)Trp
      significantly inhibited keratinocyte activation with decrease in IL-6 production
      and p-Erk1/2 and p-STAT3 expression. 5(OH)Trp also inhibited the differentiation
      of IFN-gamma- and IL-17A-expressing CD4+ T cells and related cytokine production
      (TNF-alpha, IL-6, IL-17A and IFN-gamma) in splenocytes. In conclusion, 5(OH)Trp
      can inhibit imiquimod-induced psoriasiform dermatitis in mice and inhibit
      activation in keratinocytes and splenocytes.

PMID- 30221418
TI  - Partial enzymatic reactions: A missed opportunity in proteomics research.
AB  - RATIONALE: Biological studies are conducted at ever-increasing rates by relying
      on proteomic workflows. Although data acquisition by mass spectrometry is highly
      automated and rapid, sample preparation continues to be the bottleneck of
      developing high-throughput workflows. Enzymatic protein processing, in
      particular, involves time-consuming protocols that can extend from one day to
      another. To address this gap, we developed and evaluated simple, in-solution
      tryptic enzymatic reactions that unfold within a few minutes, and demonstrate the
      utility of the methodology for the rapid analysis of proteins originating from
      cancer cell extracts. METHODS: Tryptic enzymatic reactions were conducted for 7
      60 min, and the results were compared with that of a routine approach conducted
      for 18 h. No other reaction conditions were changed relative to the 18 h
      procedure. The reaction products were analyzed by nanospray high-performance
      liquid chromatography/tandem mass spectrometry (nano-HPLC/MS/MS), and the quality
      of the products was assessed in terms of peptide/protein identifications,
      sequence coverage, peptide length, missed-cleavage sites, quality of generated
      ions, and peptide hydrophilic/hydrophobic properties. RESULTS: The results
      demonstrate that brief, and therefore incomplete, enzymatic processes lead to a
      large number of peptide fragments that improve protein sequence and proteome
      coverage, that the tandem mass spectra produced from these peptides are of high
      quality for reliable protein identifications, and that the physical properties of
      peptides are prone to supporting the development of alternative multi-dimensional
      separations and middle-down proteomics analysis strategies. The reproducibility
      of generating the same peptides within a few minutes of enzymatic digestion was
      remarkably close to that obtained from 18 h long reactions, and the combined
      results of short and long reactions increased proteome coverage by ~40%.
      CONCLUSIONS: We demonstrate that partial enzymatic reactions conducted on short
      time-scales represent a valuable asset to proteomic studies, and propose their
      implementation either as simple, cost-effective, stand-alone protocols for
      substantially streamlining the analysis of biological samples, or as
      complementary protocols, for improving protein sequence and proteome coverage.

PMID- 30221420
TI  - Commentary on "Methodologic limitations of prescription opioid safety research
      and recommendations for improving the evidence base".

PMID- 30221422
TI  - Nursing work environment, value congruence and their relationships with nurses'
      work outcomes.
AB  - AIMS: To explore the relationships between work environment, value congruence and
      nurses' work outcomes; as well as to test the moderating effects of value
      congruence. BACKGROUND: A poor nursing work environment in most of mainland China
      has negatively influenced nurses' job satisfaction, burnout and turnover
      intention. New insights such as improving nurses' value congruence should be
      proposed to better foster nurses. METHODS: Cross-sectional data were selected
      from the Chinese Nurses' Environment of Work Status study. In total, 19149 valid
      samples were collected. Hierarchical regression analyses and simple slope
      analyses were performed. RESULTS: The correlation coefficients of the variables
      were all significant (p < .01) and in the expected direction. Value congruence
      moderated the relationship between nursing work environment and burnout
      (emotional exhaustion: beta = 0.106, p < .01; depersonalization: beta = 0.111, p
      < .01). CONCLUSIONS: Nursing work environment and value congruence were
      positively related to job satisfaction, and negatively related to burnout and
      turnover intention. The adverse impact of poor work environment on nurses'
      burnout can be buffered if nurses' value congruence is compatible with that of
      the organisation. IMPLICATIONS FOR NURSING MANAGEMENT: Except for improving the
      organisational characteristics, value congruence is a useful concept that
      managers can leverage to improve positive outcomes for both the organisation and
      its nurses.

PMID- 30221421
TI  - Differential uptake of herpes zoster vaccination associated with socioeconomic
      status: A population-based study in Stockholm County, Sweden.
AB  - PURPOSE: To investigate whether herpes zoster vaccine (HZV) was associated with
      socioeconomic status in Stockholm, when the vaccine was reimbursed in Sweden.
      METHODS: This was an observational retrospective case-control study, using
      population-based health care registers. During the study period, September 2013
      to November 2014, the HZV was reimbursed as part of the National Pharmaceutical
      Benefits Scheme in Sweden and recommended for individuals over 50 years. A case
      was any person, living in Stockholm County, who received HZV during the study
      period. For each case, 10 (unvaccinated) controls living in Stockholm County were
      selected and matched by age and sex. In total, 9099 cases and 89 736 controls
      were included. Socioeconomic variables investigated included education, income,
      immigration status, and marital status. We also investigated whether HZV was
      associated with the Charlson Comorbidity Index (CCI), and/or previous herpes
      zoster diagnosis. RESULTS: Mean age at vaccination was 69.8 years, and 65.8% of
      vaccinees were women. There was a positive association between vaccination and
      higher education (OR = 3.4 (95% CI 3.0-3.8) for men and OR = 2.8 (95% CI 2.6-3.0)
      for women, respectively) in comparison to primary education. Higher income and
      being married were positively associated with vaccination, particularly for men,
      whereas being an immigrant was negatively associated. There was a negative
      association between a higher CCI score and HZV, indicating that healthier
      individuals were more likely to have been vaccinated. CONCLUSIONS: Despite the
      vaccine being part of the National Pharmaceutical Benefit Scheme, receipt of the
      HZV was significantly associated with socioeconomic factors.

PMID- 30221423
TI  - Asymmetric Copolymers: Synthesis, Properties, and Applications of Gradient and
      Other Partially Segregated Copolymers.
AB  - Asymmetric copolymers are a class of materials with intriguing properties. They
      can be defined by a distribution of monomers within the polymer chain that is
      neither strictly segregated, as in the case of block copolymers, nor evenly
      distributed throughout each chain, as in the case of statistical copolymers. This
      definition includes gradient copolymers as well as block copolymers that contain
      segments of statistical copolymer. In this review, different methods to
      synthesize asymmetric copolymers are first discussed. The properties of
      asymmetric copolymers are investigated in comparison to those of block and random
      counterparts of similar composition. Finally, some examples of applications of
      asymmetric copolymers, both academic and industrial, are demonstrated. The aim of
      this review is to provide a perspective on the design and synthesis of asymmetric
      copolymers with useful applications.

PMID- 30221424
TI  - Development and pharmacist-mediated use of tools for monitoring atypical
      antipsychotic-induced side effects related to blood glucose levels.
AB  - PURPOSE: Drug side effects often lead to serious outcomes. Administration of
      second-generation antipsychotics has resulted in diabetic ketoacidosis and
      diabetic coma leading to death. Therefore, pharmacists are required to collect
      information on clinical test values, determine the appropriate test timing, and
      coordinate with doctors for further clinical laboratory orders, all of which are
      labor-intensive and time-intensive tasks. In this study, we developed a side
      effect-monitoring tool and aimed to clarify the influence and efficiency of
      monitoring side effects by using the tool in patients taking atypical
      antipsychotics in whom it is necessary to check clinical test values such as
      blood sugar levels. METHODS: We extracted clinical test values for patients
      treated with second-generation antipsychotics from electronic medical records.
      The test values are automatically displayed in the side effect grade
      classification specified by CTCAE ver. 4.0. A database was constructed using
      scripts to provide alerts for the timing of clinical testing. The pharmacist used
      this tool to confirm clinical test values for patients taking medication and
      requested the physician to inspect orders based on the appropriate test timings.
      RESULTS: The management tool reduced the pharmacists' effort in collecting
      information on patients' prescription status and test values. It enabled patients
      to undergo tests at the appropriate time according to the progression of glucose
      metabolism and allowed for easy monitoring of side effects. CONCLUSIONS: The
      results suggested that regardless of pharmacists' experience or skill, the
      introduction of this tool enables centralization of side effect monitoring and
      can contribute to proper drug use.

PMID- 30221425
TI  - Comparison of enzyme-linked immunosorbent assay with indirect immunofluorescence
      assay for the diagnosis of Mycoplasma pneumoniae infection.
AB  - BACKGROUND: The study aimed to compare enzyme-linked immunosorbent assay (ELISA)
      with indirect immunofluorescence assay (IFA) in the diagnosis of Mycoplasma
      pneumoniae infection. METHODS: From March 2016 to May 2017, 180 patients
      suspected with M. pneumoniae infection were enrolled. The SeroMP kit using ELISA
      and PNEUMOSLIDE kit using IFA were performed in parallel to detect the IgM
      antibodies against M. pneumoniae. Cohen's kappa statistics were used to assess
      the agreement between the ELISA and IFA assays, multivariate logistic regression
      analysis was used to evaluate risk factors for the discordance between the ELISA
      and IFA assays. RESULTS: The mean age of the enrolled subjects was 46.6 +/- 21.1
      years. For detection of M. pneumoniae infection, the positivities of the ELISA
      and IFA assays were 15.6% (95% CI: 11.0%, 21.6%) and 10.0% (95% CI: 6.4%, 15.3%),
      respectively. The total positivity was 19.4% (95% CI: 14.3%, 25.8%). The
      agreement between the ELISA and IFA assays was low (kappa = 0.117, P < 0.001).
      Variables associated with discordant results between ELISA and IFA assays in
      multivariate analysis were as follows: male (OR: 0.366; 95% CI: 0.149, 0.899; P <
      0.05), age (>33 years old; OR: 0.313; 95% CI: 0.129, 0.758; P < 0.05).
      CONCLUSION: In detection of M. pneumoniae infection, low agreement was found in
      IgM assays between the ELISA and IFA methods, female and younger age were
      significant risk factors for the discordance. A combination of ELISA and IFA
      tests would be recommended, in order to detect more patients suspected of M.
      pneumoniae infection in clinical practice.

PMID- 30221426
TI  - Violence-prevention climate in the turnover intention of nurses experiencing
      workplace violence and work frustration.
AB  - AIMS: To determine the moderating effect of a violence-prevention climate and the
      mediating effect of work frustration on the relationship between workplace
      violence (WPV) and the turnover intention of nurses. BACKGROUND: To maintain the
      stability and work quality of nurses, WPV should be studied to provide effective
      prevention measures. METHODS: A cross-sectional study with a convenience sample
      was adopted. Participants were nurses from three hospitals in Taiwan. Of 1,531
      questionnaires, 973 were valid for analysis (63.6%). RESULTS: A total mediating
      effect of work frustration on nurses' own experiences of WPV increased turnover
      intention. Witnessing WPV toward coworkers caused a significant partial mediating
      effect on work frustration that further increased turnover intention. A violence
      prevention climate had a significant moderating effect on the work frustration
      and turnover intention of nurses after they had witnessed violence against
      others. CONCLUSION: Effective policies and an incentivized reporting system can
      foster a safe and friendly work environment not only for nurses who experience
      violence but also for those who witness violence. IMPLICATIONS FOR NURSING
      MANAGEMENT: Nursing managers and leaders must create a positive consultative
      pipeline to ensure a safe climate and environment for both the victims of WPV and
      the nurses who witness violence against others.

PMID- 30221427
TI  - Commentary on Bhattacharya et al. (2018): Reliance of the alcohol industry on
      heavy drinkers makes case against industry involvement in alcohol policy.

PMID- 30221428
TI  - Porous graphite sheet spray ionization ion mobility spectrometry.
AB  - In this work, a porous graphite sheet is introduced as the substrate in a spray
      ionization source for ion mobility spectrometry (PGSI-IMS) for the first time.
      This ionization source has some important advantages in comparison with the
      hollow needle, which is conventionally used in electrospray ionization. In order
      to prepare the hydrophilic surface needed to load samples on a graphite
      substrate, the graphite sheet was treated with hot sulfuric acid solution for 2
      hours. Some parameters affecting the ionization efficiency were studied, and the
      optimized conditions were found to be 3.5-kV graphite voltage, 24-MUL methanol
      flow rate, 500 mL min-1 the gas flow rate, and graphite sheet with a 60 degrees 
      tip angle and 3-mm distance from the counter electrode. Finally, analyses of some
      test compounds (imipramine, diclofenac, codeine, morphine, and ethion) were
      conducted to evaluate the capability of the new ionization source in the positive
      and negative modes. The satisfactory results proved the capability of the
      graphite sheet spray ionization, to be conveniently used for routine analysis of
      chemical compounds by IMS.

PMID- 30221429
TI  - An observational study of the use of acute hospital care by people with
      intellectual disabilities in England.
AB  - INTRODUCTION: Providing safe, high-quality admitted-patient care for people with
      intellectual disabilities (IDs) requires consideration for their special needs
      particularly in relation to communication and consent. To make allowance for
      these special requirements, it would be helpful for hospitals to know how often
      they are likely to arise. This study set out to identify the amount and patterns
      of use of acute, non-psychiatric hospital admitted-patient care in England by
      people with ID. Patterns are considered in relation to clinical specialties,
      modes of admission (emergency or planned) and life stages (children and young
      people, working age and older adults). In each case, patterns for people with ID
      are compared with patterns for those without. METHODS: Descriptive observational
      study using a major general practitioner (GP) research database (Clinical
      Practice Research Datalink GOLD) linked to routine national statistical records
      of admitted-patient care. RESULTS: Overall people identified by their GP as
      having ID had higher rates of admitted-patient care episodes and longer durations
      of stay than those without. Differences varied considerably between clinical
      specialties with rates more elevated in medical and paediatric than surgical
      specialties. Admitted-patient care rates for women with ID in obstetrics and
      gynaecology were lower than for other women, while rates for admitted-patient
      dental care were much higher for both men and women with ID. In an average
      English health administrative area with a local population of 250 000 people, at
      any time, there are likely to be approximately 670 people receiving acute
      admitted-patient care. Approximately six of these are likely to have been
      identified by their GP as having ID. At 0.9% of hospital in-patients, this is
      just under twice the proportion in the population. CONCLUSION AND IMPLICATIONS:
      Our figures are likely to be an underestimate as GP identification of people with
      ID is known to be far from complete. However, they indicate that the number of
      people with ID in acute hospital settings is likely to be substantially more than
      a recent survey of English health services indicated they were aware of. The
      study is intended to help guide expectations for acute hospitals seeking to audit
      the completeness of their identification of people with ID and to indicate their
      likely distribution between clinical specialties.

PMID- 30221430
TI  - Mineral composition of cow milk from multibreed herds.
AB  - This study estimated the effect of Holstein-Friesian, Brown Swiss, Jersey,
      Simmental and Alpine Grey cattle breeds on milk mineral contents (Ca, Mg, P, K,
      and Na) in multibreed herds using data predicted with mid-infrared spectroscopy.
      The dataset included 139,821 observations from 16,566 cows and 977 herds. Fixed
      effects considered in the mixed model were breed, parity, stage of lactation and
      first-order interactions, and random effects were cow, herd-test-date, and the
      residual. Multiple comparisons of least squares means were performed for the main
      effect of breed, parity, and stage of lactation using Bonferroni adjustment.
      Holstein-Friesian yielded milk with the lowest fat, protein, and casein
      concentration, and Ca, Mg, and P contents, whereas Jersey cows produced milk with
      the greatest fat, protein, and casein concentration, and Ca and Mg contents.
      Results of this study suggest that mixing milk from different breeds could
      enhance milk composition and technological ability, and therefore contribute to
      improve dairy industry efficiency.

PMID- 30221431
TI  - Exploration of the dialogue components in Avatar Therapy for schizophrenia
      patients with refractory auditory hallucinations: A content analysis.
AB  - Auditory verbal hallucinations are hallmark symptoms of schizophrenia and are
      amongst the most disturbing symptoms of the disorder. Although not entirely
      understood, the relationship between the voice hearer and their voices has been
      shown to be an important treatment target. Understanding voice hearers'
      standpoints through qualitative analysis is central to apprehend a deeper
      comprehension of their experience and further explore the relevance of
      interpersonal interventions. Compared with other dialogical intervention, virtual
      reality-assisted therapy (Avatar Therapy) enables patients to be in a tangible
      relation with a representation of their persecutory voice. This novel therapy has
      shown favourable results, though the therapeutic processes remain equivocal. We
      consequently sought to begin by characterizing the main themes emerging during
      the therapy by exploring the hearer's discussion with their avatar. The therapy
      sessions of 12 of our referrals were transcribed, and the patients' responses
      were analysed using content analysis methods. Five themes emerged from data
      saturation: emotional responses to the voices, beliefs about voices and
      schizophrenia, self-perceptions, coping mechanisms, and aspirations. All patients
      had at least one element within each of these themes. Our analyses also enabled
      us to identify changes that were either verbalized by the patients or noted by
      the raters throughout therapy sessions. These findings are relevant as they
      allowed to identify key themes that are hypothesized to be related to therapeutic
      targets in a novel relational therapy using virtual reality. Future studies to
      further explore the processes implicated within Avatar Therapy are necessary.

PMID- 30221432
TI  - Ascidiacyclamides containing oxazoline and thiazole motifs assume square
      conformations and show high cytotoxicity.
AB  - Four cyclic octapeptides were designed from ascidiacyclamide [cyclo(-Ile-Oxz-D
      Val- Thz-)2 ] (ASC, 1) to investigate the effects of oxazoline (Oxz) and thiazole
      (Thz) rings on the structures and cytotoxicities of the peptides. cyclo(-Ile-Thz
      D-Val-Oxz-)2 (2) had the same number of Oxz and Thz rings as ASC, but the ring
      positions were switched. cyclo(-Ile-Oxz-D-Val-Thz-Ile-Thz-D-Val-Thz-) (3) and
      cyclo(-Ile-Thz-D-Val-Oxz-Ile-Thz-D-Val-Thz-) (4) contained one Oxz and three Thz
      rings within the molecule. All Oxz rings were substituted with Thz in cyclo(-Ile
      Thz-D-Val-Thz-)2 (5). These analogues had new Oxz and Thz blocks forming the 24
      membered ring. Based on CD spectra and X-ray diffraction analyses, the structures
      of all four analogues were classified as square ASC forms. But the structures of
      2 and 5 differed from the original square form of 1, and they showed no
      cytotoxicity. The structure of 3 was very similar to that of 1, and 3 showed 10
      times greater cytotoxicity than 1. Although no definite structure of 4 was
      obtained, it showed three times greater cytotoxicity than 1. It appears that the
      position and number of Oxz residues are essential determinants in the structure
      cytotoxicity relationship of ASC analogues.

PMID- 30221433
TI  - A visual affective analysis of mass media interventions to increase antimicrobial
      stewardship amongst the public.
AB  - OBJECTIVES: In an innovative approach to improve the contribution of health
      psychology to public health we have analysed the presence and nature of affect
      within the visual materials deployed in antimicrobial stewardship interventions
      targeting the public identified through systematic review. DESIGN: A qualitative
      analysis focused on the affective content of visual materials garnered from a
      systematic review of antibiotic stewardship (k = 20). METHODS: A novel method was
      devised drawing on concepts from semiotics to analyse the affective elements
      within intervention materials. RESULTS: Whilst all studies examined tacitly rely
      on affect, only one sought to explicitly deploy affect. Three thematic categories
      of affect are identified within the materials in which specific ideological
      machinery is deployed: (1) monsters, bugs, and superheroes; (2) responsibility,
      threat, and the misuse/abuse of antibiotics; (3) the figure of the child.
      CONCLUSIONS: The study demonstrates how affect is a present but tacit
      communication strategy of antimicrobial stewardship interventions but has not -
      to date - been adequately theorized or explicitly considered in the intervention
      design process. Certain affective features were explored in relation to the
      effectiveness of antimicrobial resistance interventions and warrant further
      investigation. We argue that further research is needed to systematically
      illuminate and capitalize upon the use of affect to effect behaviour change
      concerning antimicrobial stewardship. Statement of contribution What is already
      known on this subject? The (mis)use of antibiotics and consequent risk of
      antimicrobial resistance is a critical public health problem. If sufficient
      action is not taken, global society will face the 'post-antibiotic' era, in which
      common infections will lead to death for many millions. Key desirable behavioural
      changes are decreased patient demands for antibiotics, use of them for targeted
      purposes alone, and compliance with prescribed dosing. There is a growth of
      interest in the role of affect in mass media interventions designed to engage
      publics and produce health-related behavioural change. What does this study add?
      This article presents a novel analytic approach to understanding and intervening
      within behaviour change in public health that may complement other types of
      analysis. We present findings specifically from an 'affective' analysis based on
      semiotics in which we critically interrogated the visual imagery being deployed
      in mass media public health interventions concerning antimicrobial stewardship.
      Three thematic categories of affect are identified within the materials in which
      specific ideological machinery is deployed and that demonstrate some association
      with intervention effectiveness worthy of further investigation and testing.

PMID- 30221434
TI  - Efficacy and tolerability of lithium for the treatment of acute mania in children
      with bipolar disorder: A systematic review: A report from the ISBD-IGSLi joint
      task force on lithium treatment.
AB  - OBJECTIVES: To assess the efficacy and tolerability of lithium for the treatment
      of acute mania in children and adolescent diagnosed with bipolar disorder.
      METHODS: A systematic literature search up to August 2017 was conducted for
      clinical trials that included lithium in males and females up to 18 years of age
      with a diagnosis of bipolar disorder and experiencing a manic or mixed episode
      according to standardized diagnostic criteria. The protocol was registered in
      PROSPERO (CRD42017055675). RESULTS: Four independent studies described in seven
      manuscripts met the inclusion criteria. Overall, 176 patients were treated with
      lithium either as a monotherapy or adjunct to risperidone. Efficacy results
      suggest that lithium may be superior to placebo (standardized mean difference
      [SMD] -0.42, 95% confidence interval [CI] -0.88 to 0.04), comparable to sodium
      divalproex (SMD -0.07, 95% CI: -0.31 to 0.18), but significantly less effective
      than risperidone for treating protracted manic/mixed episodes and comorbid
      attention-deficit hyperactivity disorder (ADHD) in prepubertal children (SMD
      0.85, 95% CI: 0.54 to 1.15). Lithium was not associated with serious adverse
      events, and was generally well tolerated with common side effects similar to
      those reported in adults. CONCLUSIONS: Limited data suggests that lithium may be
      an effective and tolerable treatment for some forms of paediatric mania. However,
      lithium is clearly inferior in efficacy to risperidone in prepubertal patients
      diagnosed with protracted manic/mixed episodes and comorbid ADHD. There is a lack
      of data concerning the efficacy and tolerability of lithium as an acute treatment
      for classical mania in adolescents and important clinical issues remain
      unaddressed.

PMID- 30221435
TI  - Underage alcohol sales in community sporting clubs.
AB  - INTRODUCTION AND AIMS: Adolescent alcohol consumption and associated harms are
      significant public health issues in Australia. One strategy to reduce this
      problem is restricting alcohol supply to adolescents below age 18. To ensure
      compliance with laws that forbid underage alcohol sales, effective monitoring
      systems that operate across a range of settings, including sporting clubs, are
      required. This study investigated compliance with regulations requiring proof of
      age identification and refusal of underage alcohol sales in community sporting
      clubs. DESIGN AND METHODS: Compliance with alcohol sales laws was monitored using
      a male confederate that appeared under 18 who attempted to purchase alcohol at
      community sporting clubs in two regional areas of Victoria, Australia during the
      2016-2017 sporting seasons. RESULTS: Purchase observations were completed at 43
      clubs (observations could not be conducted at 14 clubs); alcohol was purchased at
      41 (95%) clubs. Four (9%) clubs asked the confederate-purchaser to provide
      identification of age-in two instances the purchaser was not sold alcohol and in
      two instances was sold alcohol after not showing identification. Rates of
      compliance with proof of age identification and alcohol sales did not vary
      according to staff- and club-related variables. DISCUSSION AND CONCLUSIONS: This
      study indicates the need for more rigorous enforcement of alcohol sales
      regulations in community sporting clubs. Community health agencies could work
      with sporting clubs to assist them to improve compliance with alcohol sales
      regulations and to provide information on the significant role clubs play in
      shaping the adolescent alcohol culture.

PMID- 30221436
TI  - Perceptions of nursing workloads and contributing factors, and their impact on
      implicit care rationing: A Queensland, Australia study.
AB  - AIMS: To explore nurses' perceptions of factors affecting workloads and their
      impact on patient care. BACKGROUND: Fiscal restraints and unpredictable patient
      illness trajectories challenge the provision of care. Cost containment affects
      the number of staff employed and the skill-mix for care provision. While
      organisations may acknowledge explicit rationing of care, implicit rationing
      takes place at the point of service as nurses are forced to make decisions about
      what care they can provide. METHOD: A self-report cross sectional study was
      conducted using an on-line survey with 2,397 nurses in Queensland, Australia.
      RESULTS: Twenty to forty per cent reported being unable to provide care in the
      time available; having insufficient staff; and an inadequate skill-mix. The
      respondents reported workload and skill-mix issues leading to implicit care
      rationing. Over 60% believed that the processes to address workload issues were
      inadequate. CONCLUSIONS: Institutional influences on staffing levels and skill
      mix are resulting in implicit care rationing. IMPLICATIONS FOR NURSE MANAGERS:
      Adequate staffing should be based on patient acuity and the skill-mix required
      for safe care. Managers should be more assertive about adequate clinical
      workloads, involve staff in decision-making, and adopt a systematic planning
      approach. Failure to do so results in implicit care rationing impacting on
      patient safety.

PMID- 30221437
TI  - The current status of intraoperative radiation therapy in breast cancer:
      Challenges and promises.

PMID- 30221438
TI  - Randomized controlled study on the effectiveness of animal-assisted therapy on
      depression, anxiety, and illness perception in institutionalized elderly.
AB  - AIM: The aim of this study was to verify dog-assisted therapy's effectiveness on
      depression and anxiety in institutionalized elderly. Patients' illness perception
      was examined to identify core beliefs regarding mood, personal control, and
      illness coherence because they can affect treatment compliance. Subjective
      perception of pain, social interaction, and setting-bound observable variables
      were also studied. METHODS: This study involved a randomized sample of
      institutionalized patients 65 years of age and older; the treatment group had 17
      subjects and the control group had 14 subjects. All patients were administered
      the Mini-Mental State Examination, 15-item Geriatric Depression Scale, Positive
      and Negative Affect Schedule, Generalized Anxiety Disorder 7, Illness Perception
      Questionnaire, and Numeric Pain Rating Scale. Intra- and inter-group data
      analysis was performed before and after treatment. Over the course of 10 weeks,
      patients participated in individual 30-min sessions. An observational methodology
      was developed to record verbal and non-verbal interactions between the elderly,
      the dog, and the dog handler. RESULTS: A large effect size and a statistically
      significant decrease in 15-item Geriatric Depression Scale scores were identified
      in the treatment group. No significant differences were detected in the
      Generalized Anxiety Disorder 7, Positive and Negative Affect Schedule, and
      Numeric Pain Rating Scale. However, the Positive and Negative Affect Schedule and
      the Numeric Pain Rating Scale showed a moderate decrease. The Illness Perception
      Questionnaire's timeline (acute/chronic) and treatment control subscales showed a
      clinically relevant, large effect size. CONCLUSIONS: Dog-assisted therapy has
      proved to be effective in reducing symptoms of depression in institutionalized
      elderly. The increase in verbal interactions with the handlers throughout the
      study suggests the dog acts as a facilitator of social interaction, eliciting
      positive emotional responses. Dog-assisted therapy shows promising results in the
      perception of illness timeline and treatment control, indicating potential
      enhancement of the sense of treatment-related empowerment. However, further study
      is required.

PMID- 30221439
TI  - FOXA2 depletion leads to mucus hypersecretion in canine airways with respiratory
      diseases.
AB  - Because of exposure to environmental pollutants, infectious agents, and genetic
      predisposition, companion animals develop respiratory illnesses similar to those
      in humans. Older dogs of smaller breeds develop canine infectious respiratory
      disease, chronic bronchitis, and chronic obstructive pulmonary disease, with
      chronic lung infection, airway goblet cell hyperplasia and metaplasia, and mucus
      hypersecretion. Excessive mucus clogs airways, reduces gas exchanges, disables
      the mucociliary clearance, and reduces drug penetration. The Forkhead box protein
      A2 (FOXA2) is a key transcriptional regulator that maintains airway mucus
      homeostasis. Prior studies have shown that FOXA2 expression is frequently
      depleted in diseased human airways. Unfortunately, FOXA2 depletion has not been
      examined in dogs. Our current study indicated that both single bacterial
      infection by Pseudomonas aeruginosa and Bordetella bronchiseptica and
      polymicrobial infection by viral/bacterial pathogens depleted FOXA2 in canine
      airways, resulting in goblet cell hyperplasia and metaplasia and excessive mucus
      production. Furthermore, P. aeruginosa virulence factor pyocyanin activated the
      antagonistic STAT6 and epidermal growth factor receptor signalling pathways to
      inhibit FOXA2. Unravelling the mechanism of FOXA2 inactivation will hasten the
      development of non-antibiotic therapeutics to improve mucociliary clearance of
      pathogens in canine airway.

PMID- 30221440
TI  - Phenolic Building Blocks for the Assembly of Functional Materials.
AB  - Phenolic materials have long been known for their use in inks, wood coatings, and
      leather tanning. However, recently there has been a renewed interest in
      engineering advanced materials from phenolic building blocks. The intrinsic
      properties of phenolic compounds, such as metal chelation, hydrogen bonding, pH
      responsiveness, redox potentials, radical scavenging, polymerization, and light
      absorbance, have made them a distinct class of structural motifs for the
      synthesis of functional materials. Materials prepared from phenolic compounds
      often retain many of these useful properties with synergistic effects in
      applications ranging from catalysis to biomedicine. The present review provides
      an overview of the diverse functional materials that can be prepared from
      phenolic building blocks, bridging the various fields currently studying and
      using phenolic compounds. Natural and synthetic phenolic compounds are first
      discussed, followed by the assembly of functional materials. The engineered
      phenolic materials are grouped under three broad categories: thin films (e.g.,
      metal-phenolic networks and polydopamine); particles (e.g., metal-organic
      frameworks and superstructures); and bulk materials (e.g., gels). Applications of
      phenolic-based materials are then presented, focusing mainly on mechanical (e.g.,
      adhesives), biological (e.g., drug delivery), and environmental and energy (e.g.,
      separation and catalysis) applications. Several examples of their emerging
      applications are also included. Finally, potential routes for the continued
      integration of disparate fields using phenolic building blocks and fundamental
      questions still requiring investigation are highlighted, and an outlook of the
      field is provided.

PMID- 30221441
TI  - Analyzing the chance of developing dementia among geriatric people: a cross
      sectional pilot study in Bangladesh.
AB  - AIM: Alzheimer's disease is the most common form of dementia, representing 60-80%
      of cases, and ageing is the primary risk factor for the development of
      Alzheimer's disease. The objective of this study was to examine the chance of
      developing dementia (i.e. mild cognitive impairment (MCI), Alzheimer's disease)
      among geriatric people in Bangladesh. METHODS: This study included 390 adult
      citizens of Bangladesh (age range: 60-70 years). The Takeda Three Colors
      Combination (TTCC) test was used to detect the prevalence of MCI and mild
      dementia among the subjects, and then the Clinical Dementia Rating was used to
      determine the level of dementia. RESULTS: The subjects who were aged 60-65 years
      included 154 with MCI, 76 with mild dementia, 1 with moderate dementia, 4 with
      severe dementia, and 29 without dementia. The subjects who were aged 66-70 years
      included 75 with MCI, 36 with mild dementia, 0 with moderate dementia, 2 with
      severe dementia, and 13 without dementia. The sensitivity of the TTCC was 75% and
      58% for the mild dementia and MCI groups, respectively, and the specificity was
      52%. The odds ratio of incorrect responses to the TTCC was 3.42 (95% confidence
      interval: 1.63-7.21) for subjects with mild dementia compared those without
      dementia. However, the TTCC outcomes revealed no significant differences between
      the MCI and non-dementia groups. The results showed no significant associations
      between cognitive decline/developing dementia and social status/occupation.
      CONCLUSION: The outcomes of this study indicated that most of the subjects had
      MCI or mild dementia and were farmers aged 60-65 years.

PMID- 30221442
TI  - Regulation of lactate metabolism in the acetogenic bacterium Acetobacterium
      woodii.
AB  - Acetogenic bacteria compete in an energy-limited environment by coupling
      different metabolic routes to their central metabolism of CO2 fixation. The
      underlying regulatory mechanisms are often still not understood. In this work, we
      analysed how lactate metabolism is regulated in the model acetogen Acetobacterium
      woodii. Construction of a DeltalctCDEF mutant and growth analyses demonstrated
      that the genes are essential for growth on lactate. Subsequent bridging PCR and
      quantitative PCR analyses revealed that the lctBCDEF genes form an operon that
      was expressed only during lactate metabolism. The lctA gene was cloned, expressed
      in Escherichia coli and purified. LctA bound to the intergenic DNA region between
      lctA and the lct operon in electromobility shift assays, and binding was revoked
      in the presence of lactate. Further restriction site protection analyses
      consolidated the lactate-dependent binding of LctA and identified the binding
      site within the DNA. Cells grew mixotrophically on lactate and another energy
      source and showed no diauxic growth. From these data, we conclude that the
      catabolic lactate metabolism is encoded by the lct operon and its expression is
      negatively regulated by the DNA-binding repressor LctA.

PMID- 30221443
TI  - Applying a cognitive-emotional model to nonsuicidal self-injury.
AB  - The recently proposed cognitive-emotional model of nonsuicidal self-injury (NSSI)
      draws on emotion regulation models and social cognitive theory to understand the
      onset, maintenance, and cessation of NSSI. We tested the prediction of the model
      that the relationship between emotional reactivity and NSSI is moderated by
      specific cognitions about self-injury (i.e., self-efficacy to resist NSSI, NSSI
      outcome expectancies), emotion regulation, and rumination. A sample of 647
      university students aged 17-25 years (M = 19.92, SD = 1.78) completed self-report
      measures of the constructs of interest. As expected, we found that emotional
      reactivity was positively related to NSSI, particularly for people who had weak
      self-efficacy to resist NSSI. However, emotional reactivity was negatively
      related to NSSI for people who were more likely to use expressive suppression to
      regulate emotion. Implications for the theoretical understanding of NSSI are
      discussed.

PMID- 30221444
TI  - Relationship between pressure ulcer risk based on Norton Scale and on the
      "Eating/Drinking" need assessment.
AB  - AIM: To study the relationship between pressure ulcer risk evaluated by the
      Norton Scale and inadequate fulfilment of Need 2 (Eating/Drinking) from the 14
      need classification designed by Virginia Henderson. BACKGROUND: Assessing
      nutritional status and skin condition to implement preventive measures are
      important nursing interventions. Our hospital's standard procedure requires
      recording Norton Scale and Henderson Eating/Drinking Assessment results. METHODS:
      This was a descriptive cross-sectional study, analysing case histories of 219
      patients in medical/surgical wards for >24 hr with nursing care recorded in the
      GACELA Care computer application. Patient sociodemographic variables and
      evaluation concepts from the Norton Scale and Eating/Drinking were studied.
      RESULTS: A statistically significant relationship (p < 0.05; 95% CI: 0.61, 2.83)
      was seen between inadequate Eating/Drinking need fulfilment and increased
      pressure ulcer risk. Pressure ulcer risk was generally low in the sample, with
      mainly no or minimum risk (77.3%); the oldest age group had the highest risk.
      Self-care autonomy was the most frequently assessed item in Eating/Drinking
      (42%). CONCLUSIONS: A relationship was found between Norton Scale risk results
      and Eating/Drinking need assessment results. The greater the pressure ulcer risk,
      the more likely was inadequate need satisfaction (poor nutritional status).
      IMPLICATIONS: To help identify pressure ulcer risk, nurses should assess
      patients' eating independence. Safeguarding nutritional status and preventing
      pressure ulcers are nursing skills associated with quality nursing care.

PMID- 30221445
TI  - Identification of a novel cytochrome P450 CYP3356A1 linked with insecticide
      detoxification in Bradysia odoriphaga.
AB  - BACKGROUND: Cytochrome P450 monooxygenases play an important role in the
      metabolic detoxification of insecticides in insect pests. However, little is
      known about the role of a specific P450 gene and its responses to insecticide
      exposure in Bradysia odoriphaga, a major pest in Chinese chive production.
      RESULTS: In this study, a novel P450 gene, CYP3356A1, was cloned from Bradysia
      odoriphaga. The full-length cDNA sequence of CYP3356A1 is 2153 bp and its open
      reading frame (ORF) encodes 508 amino acids. Quantitative real time PCR(qRT-PCR)
      analyses in different tissues showed that CYP3356A1 expression was the highest in
      the Malpighian tubule. Moreover, among the different developmental stages of the
      insect, the highest expression of CYP3356A1 was found in fourth-instar larvae.
      Expression of CYP3356A1 was upregulated by treatment with imidacloprid,
      thiamethoxam, and beta-cypermethrin at median lethal concentrations (LC50 ). RNA
      interference (RNAi)-mediated silencing of CYP3356A1 significantly increased
      mortality by 36.90%, 25.17%, and 36.73 when fourth-instar B. odoriphaga larvae
      were exposed to imidacloprid, thiamethoxam, and beta-cypermethrin, respectively,
      at the LC50 dose. CONCLUSION: These results demonstrate that CYP3356A1 is related
      to the detoxification of imidacloprid, thiamethoxam, and beta-cypermethrin in B.
      odoriphaga. Moreover, the study also increased our understanding of the molecular
      mechanisms of insecticide detoxification in this pest insect. (c) 2018 Society of
      Chemical Industry.

PMID- 30221446
TI  - A case study of an adaptive design for a clinical trial with 2 doses and 2
      endpoints in a rare disease area.
AB  - Patient recruitment is challenging in rare disease clinical trials. To save time
      and resources, an inferential seamless phase II/III clinical trial design is
      considered for a clinical trial in a rare disease area. In particular, 2 doses
      compared to a placebo control are evaluated at phase II (ie, stage I). Based on
      the results of a phase II intermediate endpoint, additional patients may be
      enrolled into the 2 doses and control, 1 selected dose and control, or none of
      the 3 treatment arms at stage II. All patients including those of unselected dose
      (s) will be followed for the measurements of the phase III (ie, stage II) primary
      and secondary endpoints and incorporated in the final analysis. Under a
      reasonable condition, the type I error rate will be controlled at the nominal
      level if the same nominal level is applied for testing a dose effect based on
      either only the data of patients of stage I (in case the dose is not selected for
      stage II) or data of patients of stages I and II combined. A graphical testing
      procedure is also introduced for multiplicity adjustments to account for the 2
      doses and 2 endpoints for the overall type I error rate control. Moreover, an
      imputation approach is proposed for conditional power calculation at stage I for
      a sample size adaptive design. Simulations are carried out under different
      parameter configurations to compare the performances of various approaches. The
      trial example is further used to illustrate the applications of the methods.

PMID- 30221447
TI  - Illustration of sexual differentiation to undergraduates with a conditional gene
      expression system.
AB  - This work describes the development and evaluation of a two-session laboratory
      class based on Tet-on technology and sex determination in the fruit fly
      Drosophila melanogaster. The Tet-on system allows conditional control of gene
      expression, when doxycycline is applied. A laboratory exercise has been developed
      to illustrate how the Tet-on technology conditionally over-expresses the key sex
      determining gene transformer (tra) during development and how to inhibit sex
      differentiation in males, results in a lack of external genitalia and sex comb
      size reduction. The laboratory practice is inexpensive and straightforward, while
      allowing students to understand well how molecular biology technology can change
      biological processes, including development. (c) 2018 by International Union of
      Biochemistry and Molecular Biology, 46(5):523-526, 2018.

PMID- 30221448
TI  - Platinum(II)-Based Supramolecular Scaffold-Templated Side-by-Side Assembly of
      Gold Nanorods through Pt???Pt and pi-pi Interactions.
AB  - The side-by-side assembly of gold nanorods (GNRs) was shown to be directed by the
      supramolecular scaffolds formed by sulfonate-containing alkynylplatium(II)
      terpyridine complexes. Driven by Pt???Pt and pi-pi stacking interactions, the
      PtII complex has a high propensity to assemble in water with the head-to-tail
      stacking arrangement to construct supramolecular scaffolds, in which the
      sulfonate groups on the terpyridine ligand at the peripheral position
      preferentially bind to the sides of the GNRs. The extent of the assembly of the
      GNRs into ladder rung-like nanostructures can be modulated by the concentration
      of the PtII complex. The Pt???Pt interaction-assisted formation of the scaffolds
      and its directed assembly of GNRs were characterized by UV/Vis spectroscopy,
      quantum-chemical modeling, electron microscopy, energy dispersed X-ray (EDX)
      analysis, and SERS. This work provides insights for the construction of higher
      ordered nano-assemblies using both Pt???Pt interactions and template-directed
      approaches.

PMID- 30221449
TI  - Frailty state transitions and associated factors in South Australian older
      adults.
AB  - AIM: Frailty is a state of decreased physiological reserve and vulnerability to
      stressors. Understanding the characteristics of those most at risk of worsening,
      or likely to improve their frailty status, are key elements in addressing this
      condition. The present study measured frailty state transitions and factors
      associated with improvement or worsening frailty status in the North West
      Adelaide Health Study. METHODS: Frailty was measured using the frailty phenotype
      (FP) and a 34-item frailty index (FI) for 696 community-dwelling participants
      aged >=65 years, with repeated measures at 4.5-year follow up. RESULTS:
      Improvement in frailty state was common for both tools (FP 15.5%; FI 7.9%). The
      majority remained stable (FP 44.4%; FI 52.6%), and many transitioned to a worse
      level of frailty (FP 40.1%; FI 39.5%). For both measures, multimorbidity was
      associated with worsening frailty among non-frail participants. Among pre-frail
      participants, normal waist circumference was associated with improvement, whereas
      older age was associated with worsening of frailty status. Among frail
      individuals, younger age was associated with improvement, and male sex and older
      age were associated with worsening frailty status. CONCLUSIONS: Frailty is a
      dynamic process where improvement is possible. Multimorbidity, obesity, age and
      sex were associated with frailty transitions for both tools. Geriatr Gerontol Int
      2018; 18: 1549-1555.

PMID- 30221450
TI  - Comparison of three mobilization protocols for peripheral blood stem cell
      apheresis with Spectra Optia continuous mononuclear cell protocol in healthy
      dogs.
AB  - Peripheral blood stem cell (PBSC) transplantation following consolidation therapy
      is a feasible treatment option for canine haematological malignancies. In
      veterinary medicine, haematopoietic stem cells are generally mobilized into
      peripheral circulation using a granulocyte colony-stimulating factor (G-CSF).
      This pilot study aimed to evaluate the haematopoietic stem cell mobilization
      effect of three different regimens for PBSC apheresis with Spectra Optia
      continuous mononuclear cell (CMNC) protocol in healthy dogs. Stem cell
      mobilization was performed using high-dose plerixafor (CXCR-4 inhibitor) alone, a
      G-CSF alone, or a combination of the low-dose plerixafor and G-CSF. Three dogs
      were assigned to each mobilization protocol. Regardless of the mobilization
      protocol, the total blood volume processed was uniformly set as 270 mL/kg and
      many PBSCs, defined as CD34+/CD45dim cells, within the apheresis product were
      compared. Changes in complete blood count, PBSC counts, and blood chemistry
      analysis were monitored before, during, and after apheresis. All dogs tolerated
      the apheresis procedure using the Spectra Optia system with minimal adverse
      effects. The mean PBSC counts of the apheresis products for plerixafor, G-CSF,
      and the combination groups were 1.3 +/- 0.24, 4.2 +/- 0.47, and 6.4 +/- 0.9 * 106
      cells/kg, respectively. The apheresis procedure using Spectra Optia CMNC protocol
      in dogs is safe and feasible. Furthermore, PBSC mobilization with a combination
      of G-CSF and plerixafor appeared more effective than either compound alone in
      mobilizing PBSC to the peripheral blood in dogs.

PMID- 30221451
TI  - Nursing and music: Considerations of Nightingale's environmental philosophy and
      phenomenology.
AB  - A philosophy of nursing is to express our considered opinion on what we believe
      to be true about the nature of the profession of nursing and provide a basis for
      nursing activities. It affirms the ethical values that we hold as fundamental to
      our practice. For many of us in nursing, our philosophy derives from Nightingale
      and phenomenology. We believe Nightingale and phenomenology are uniquely placed
      within nursing philosophies, to assist the nurse to understand the use of music
      within a holistic, caring-healing paradigm, as nursing continues to adapt and
      evolve in the 21st century. This article proposes that both Nightingale's
      environmental philosophy and phenomenology are excellent intellectual and
      practice frameworks for nurses to consider music-based interventions for older
      adults who experience dementia. The potential outcome is an enhanced
      understanding of the well-being of this vulnerable group of older persons.

PMID- 30221453
TI  - Forcheurs Jean-Marie Lehn Prize: V. Artero and B. Dietzek / Tetrahedron Young
      Investigator Award in Bioorganic and Medicinal Chemistry: M. J. Fuchter / Sixth
      Polymer International-IUPAC Award: C. Boyer.

PMID- 30221452
TI  - Expression of exogenous dsRNA by Lecanicillium attenuatum enhances its virulence
      to Dialeurodes citri.
AB  - BACKGROUND: Dialeurodes citri is an important pest in citrus-producing areas of
      the world. Lecanicillium attenuatum parasitizes D. citri and kills it, suggesting
      a potential approach for the biological control of pests. However, the low
      virulence of the fungus and its slow rate of killing have limited its commercial
      competitiveness. The objective reason for these disadvantages is immunological
      rejection by the host. Our strategy was to use fungi to express the double
      stranded RNA (dsRNA) of the host immune genes. The fungal hyphae release siRNA at
      the time of infection, thus interfering with the expression of immune genes in
      the host and facilitating fungal invasion. RESULTS: We selected prophenoloxidase
      (DcPPO), prophenoloxidase-activating factor (DcPPO-AF), and lysozyme (DcLZM) as
      target genes to construct intron-splicing hairpin RNA expression vectors and to
      successfully obtain transgenic fungi. Two days after infection, the immune genes
      of D. citri showed varying degrees of silencing compared with those in the
      positive control group. The median lethal concentration (LC50 ; spores mL-1 )
      values of La::GFP, La::DcPPO, La::DcPPO-AF, and La::DcLZM were 9.63 * 104 , 2.66
      * 104 , 1.21 * 105 , and 3.31 * 104 , respectively. The 50% lethal time (LT50 )
      values of these fungi were 5.15, 3.60, 5.34, and 4.04 days, respectively. The
      virulence of La::DcPPO and La::DcLZM increased 3.62- and 2.91-fold, respectively,
      and their LT50 decreased by 30.10% and 21.55%, respectively. CONCLUSIONS: The
      results indicate that this method, which uses tens of thousands of hyphae to
      inject dsRNA to improve the virulence of transgenic fungi, can play a greater
      role in the prevention and control of pests in the future. (c) 2018 Society of
      Chemical Industry.

PMID- 30221454
TI  - Interventions to support shared decision making for hypertension: A systematic
      review of controlled studies.
AB  - BACKGROUND: Hypertension (high blood pressure) is a common long-term health
      condition. Patient involvement in treating and monitoring hypertension is
      essential. Control of hypertension improves population cardiovascular outcomes.
      However, for an individual, potential benefits and harms of treatment are finely
      balanced. Shared decision making has the potential to align decisions with the
      preferences and values of patients. OBJECTIVE: Determine the effectiveness of
      interventions to support shared decision making in hypertension. SEARCH STRATEGY:
      Searches in MEDLINE, EMBASE, CINAHL, Web of Science and PsycINFO up to 30
      September 2017. ELIGIBILITY CRITERIA: Controlled studies evaluating the effects
      of shared decision-making interventions for adults with hypertension compared
      with any comparator in any setting and reporting any outcome measures. RESULTS:
      Six studies (five randomized controlled trials) in European primary care were
      included. Main intervention components were as follows: training for health-care
      professionals, decision aids, patient coaching and a patient leaflet. Four
      studies, none at low risk of bias, reported a measure of shared decision making;
      the intervention increased shared decision making in one study. Four studies
      reported blood pressure between 6 months and 3 years after the intervention;
      there was no difference in blood pressure between intervention and control groups
      in any study. Lack of comparability between studies prevented meta-analysis.
      CONCLUSIONS: Despite widespread calls for shared decision making to be embedded
      in health care, there is little evidence to inform shared decision making for
      hypertension, one of the most common conditions managed in primary care.

PMID- 30221456
TI  - (1-aryloxy-2-hydroxypropyl)-phenylpiperazine derivatives suppress Candida
      albicans virulence by interfering with morphological transition.
AB  - Clinical treatment of Candida albicans infections has become more difficult due
      to the limited development of antifungal agents and the rapid emergence of drug
      resistance. In this study, we demonstrate the synthesis of a series of piperazine
      derivatives and the evaluation of their inhibitory activity against C. albicans
      virulence. Thirty-four (1-aryloxy-2-hydroxypropyl)-phenylpiperazine derivatives,
      including 25 new compounds, were synthesized and assessed for their efficacy
      against the physiology and pathogenesis of C. albicans. Several compounds
      strongly inhibited the morphological transition and virulence of C. albicans
      cells, although they did not influence the growth rate of the fungal pathogen. A
      leading novel compound, (1-(4-ethoxyphenyl)-4-(1-biphenylol-2-hydroxypropyl)
      piperazine), significantly attenuated C. albicans virulence by interfering with
      the process of hyphal development, but it showed no cytotoxicity against human
      cells at a micromolar level. These findings suggest that (1-aryloxy-2
      hydroxypropyl)-phenylpiperazine derivatives could potentially be developed as
      novel therapeutic agents for the clinical treatment of C. albicans infections by
      interfering with morphological transition and virulence.

PMID- 30221457
TI  - Reduction in insulin degludec dosing for multiple exercise sessions improves time
      spent in euglycaemia in people with type 1 diabetes: A randomized crossover
      trial.
AB  - AIMS: To compare the time spent in specified glycaemic ranges in people with type
      1 diabetes (T1D) during 5 consecutive days of moderate-intensity exercise while
      on either 100% or 75% of their usual insulin degludec (IDeg) dose. MATERIALS AND
      METHODS: Nine participants with T1D (four women, mean age 32.1 +/- 9.0 years,
      body mass index 25.5 +/- 3.8 kg/m2 , glycated haemoglobin 55 +/- 7 mmol/mol (7.2%
      +/- 0.6%) on IDeg were enrolled in the trial. Three days before the first
      exercise period, participants were randomized to either 100% or 75% of their
      usual IDeg dose. Participants exercised on a cycle ergometer for 55 minutes at a
      moderate intensity for 5 consecutive days. After a 4-week wash-out period,
      participants performed the last exercise period for 5 consecutive days with the
      alternate IDeg dose. Time spent in specified glycaemic ranges, area under the
      curve and numbers of hypoglycaemic events were compared for the 5 days on each
      treatment allocation using a paired Students' t test, Wilcoxon matched-pairs
      signed-rank test and two-way ANOVA. RESULTS: Time spent in euglycaemia over 5
      days was greater for the 75% IDeg dose versus the 100% IDeg dose (4008 +/- 938
      minutes vs. 3566 +/- 856 minutes; P = 0.04). Numbers of hypoglycaemic events (P =
      0.91) and time spent in hypoglycaemia (P = 0.07) or hyperglycaemia (P = 0.38) was
      similar for both dosing schemes. CONCLUSIONS: A 25% reduction in usual IDeg dose
      around regular exercise led to more time spent in euglycaemia, with small effects
      on time spent in hypo- and hyperglycaemia.

PMID- 30221458
TI  - Brain vasopressin signaling modulates aspects of maternal behavior in lactating
      rats.
AB  - The brain vasopressin system mediates various social behaviors as has been
      studied mostly in males. Only recently, advances in social neuroscience revealed
      that central vasopressin signaling via its V1a and V1b receptors also facilitates
      female social behavior, including maternal behavior. In this review, we show how
      maternal care, maternal motivation and maternal aggression of lactating rat
      mothers are modulated in a V1 receptor subtype- and brain region-specific manner.
      Measuring local release pattern of vasopressin via intracerebral microdialysis in
      the behaving rat mother as well as using pharmacological approaches to activate
      or block vasopressin receptors with subsequent behavioral observation provide
      detailed insight into the functional role of the vasopressin system in maternal
      behavior. In this context, the complementary rat animal model of high (HAB) and
      low anxiety-related behavior (LAB) is particularly helpful due to the genetically
      determined high activity of the vasopressin gene in HAB rats, which also
      underlies their high levels of maternal behavior. Furthermore, first studies in
      humans indicate that the vasopressin system in general and the V1a receptor in
      more particular might mediate mothering.

PMID- 30221455
TI  - Chinese multidisciplinary expert consensus: Guidelines on percutaneous
      transthoracic needle biopsy.
AB  - Biopsy has been used to diagnose thoracic diseases for more than a century.
      Percutaneous needle biopsy plays a crucial role in the diagnosis, staging, and
      treatment planning for tumors in the lungs, thoracic wall, hilum, and
      mediastinum. With the continuous improvement in imaging techniques, the range of
      clinical applications for percutaneous needle biopsy is also expanding. It has
      become important to improve Chinese professionals' and technicians' understanding
      of percutaneous transthoracic needle biopsy (PTNB) in order to standardize
      operating procedures and to strengthen perioperative management. However, there
      is currently no Chinese expert consensus that provides systematic standardization
      and guidance for PTNB in clinical practice. The Committee of Chinese Society of
      Interventional Oncology (CSIO) of the Chinese Anti-Cancer Association (CACA)
      initiated a Chinese multidisciplinary expert consensus on PTNB. The consensus
      includes image-guided methods, indications, contraindications, multidisciplinary
      team recommendations, biopsy procedures, daytime/outpatient biopsy,
      complications, pathological examination, and management of negative results.

PMID- 30221460
TI  - Abstract Proceedings of the 31st Annual Meeting of the International Society for
      Laboratory Hematology, Brussels, Belgium, 10-12 May 2018.

PMID- 30221459
TI  - Application of Bayesian analyses to doubly randomized delayed start, matched
      control designs to demonstrate disease modification.
AB  - Disease modification is a primary therapeutic aim when developing treatments for
      most chronic progressive diseases. The best treatments do not simply affect
      disease symptoms but fundamentally improve disease course by slowing, halting, or
      reversing disease progression. One of many challenges for establishing disease
      modification relates to the identification of adequate analytic tools to show
      differences in a disease course following intervention. Traditional approaches
      rely on the comparisons of slopes or noninferiority margins. However, it has
      proven difficult to conclusively demonstrate disease modification using such
      approaches. To address these challenges, we propose a novel adaptation of the
      delayed start study design that incorporates posterior probabilities identified
      by hierarchical Bayesian inference approaches to establish evidence for disease
      modification. Our models compare the size of treatment differences at the end of
      the delayed start period with those at the end of the early start period.
      Simulations that compare several models are provided. These include general
      linear models, repeated measures models, spline models, and model averaging. Our
      work supports the superiority of model averaging for accurately characterizing
      complex data that arise in real world applications. This novel approach has been
      applied to the design of an ongoing, doubly randomized, matched control study
      that aims to show disease modification in young persons with schizophrenia (the
      Disease Recovery Evaluation and Modification (DREaM) study). The application of
      this Bayesian methodology to the DREaM study highlights the value of this
      approach and demonstrates many practical challenges that must be addressed when
      implementing this methodology in a real world trial.

PMID- 30221461
TI  - Efficiency of natural substances to protect Beauveria bassiana conidia from UV
      radiation.
AB  - BACKGROUND: Solar radiation is assumed to be a major factor limiting the efficacy
      of entomopathogenic fungi used as biocontrol agents in open field applications.
      We evaluated 12 natural UV-protective co-formulants for their effect on the
      survival of UV-exposed Beauveria bassiana spores on agar plates, colza leaf discs
      and in the field. RESULTS: Colony-forming unit (CFU) counts of unformulated
      conidia on agar plates and leaf discs dropped to <= 50% after exposure to UV
      radiation. The highest UV protection was achieved with humic acid, which provided
      > 90% protection of UV-B-exposed conidia in laboratory experiments. In the field,
      10% humic acid increased spore persistence up to 87% at 7 days after application.
      Sesame and colza oil also provided high UV protection in both assays (> 73% and >
      70%, respectively). CONCLUSIONS: This study shows that it is possible to increase
      the persistence of B. bassiana spores under exposure to UV radiation by
      formulation with natural UV-protective additives. UV protectants might,
      therefore, increase the efficacy of entomopathogenic fungi as biocontrol agents
      in open field applications. (c) 2018 The Authors. Pest Management Science
      published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

PMID- 30221462
TI  - Development of a dedicated phantom for multi-target single-isocentre stereotactic
      radiosurgery end to end testing.
AB  - PURPOSE: The aim of this project was to design and manufacture a cost-effective
      end-to-end (E2E) phantom for quantifying the geometric and dosimetric accuracy of
      a linear accelerator based, multi-target single-isocenter (MTSI) frameless
      stereotactic radiosurgery (SRS) technique. METHOD: A perspex Multi-Plug device
      from a Sun Nuclear ArcCheck phantom (Sun Nuclear, Melbourne, FL) was enhanced to
      make it more applicable for MTSI SRS E2E testing. The following steps in the SRS
      chain were then analysed using the phantom: magnetic resonance imaging (MRI)
      distortion, planning computed tomography (CT) scan and MRI image registration
      accuracy, phantom setup accuracy using CBCT, dosimetric accuracy using ion
      chamber, planar film dose measurements and coincidence of linear accelerator mega
      voltage (MV), and kilo-voltage (kV) isocenters using Winston-Lutz testing (WLT).
      RESULTS: The dedicated E2E phantom was able to successfully quantify the
      geometric and dosimetric accuracy of the MTSI SRS technique. MRI distortions were
      less than 0.5 mm, or half a voxel size. The average MRI-CT registration accuracy
      was 0.15 mm (+/-0.31 mm), 0.20 mm (+/-0.16 mm), and 0.39 mm (+/-0.11 mm) in the
      superior/inferior, left/right and, anterior/posterior directions, respectively.
      The phantom setup accuracy using CBCT was better than 0.2 mm and 0.1 degrees .
      Point dose measurements were within 5% of the treatment planning system predicted
      dose. The comparison of planar film doses to the planning system dose
      distributions, performed using gamma analysis, resulted in pass rates greater
      than 97% for 3%/1 mm gamma criteria. Finally, off-axis WLT showed MV/kV
      coincidence to be within 1 mm for off-axis distances up to 60 mm. CONCLUSION: A
      novel, versatile and cost-effective phantom for comprehensive E2E testing of MTSI
      SRS treatments was developed, incorporating multiple detector types and fiducial
      markers. The phantom is capable of quantifying the accuracy of each step in the
      MTSI SRS planning and treatment process.

PMID- 30221464
TI  - Commentary on McGorry et al.'s Debate on: "Is 'early intervention' in bipolar
      disorder what it claims to be?"

PMID- 30221463
TI  - The different perspectives of patients, informal caregivers and professionals on
      patient involvement in primary care teams. A qualitative study.
AB  - BACKGROUND: Patient involvement in the decision-making process, especially for
      chronically ill elderly patients, has become an important element of patient
      centred primary care in many countries, including the Netherlands. This study
      openly explores different perspectives of patients, informal caregivers and
      primary care professionals on patient involvement in primary care team
      interactions. METHODS: Sixty-four qualitative semi-structured interviews with
      chronically ill elderly patients, informal caregivers and primary care
      professionals from various disciplines. Underpinned by a phenomenology approach,
      this study used conventional content analysis for data analysis. RESULTS:
      Participants have different views of the roles of patients and informal
      caregivers in the primary care team and thus different expectations of the extent
      and level of patient involvement. Three challenges impact patient involvement in
      the team: (a) patients feel misunderstood and less involved that they would like
      when professionals take control, (b) patients have to balance the conflicting
      opinions of different professionals and (c) informal caregivers act undesirably
      as team leaders due to their own view of the level of patient involvement.
      DISCUSSION AND CONCLUSION: Patient involvement is formed in complex interactions
      between patients, informal caregivers and multiple professionals whose
      perspectives and expectations can be misaligned. Recognizing the value of
      patients and informal caregivers on the team could help professionals to
      understand them better and thus limit the likelihood of challenges arising in
      team interactions.

PMID- 30221465
TI  - Influence of Sulfur-Containing Diamino Acid Structure on Covalently Crosslinked
      Copolypeptide Hydrogels.
AB  - Biologically occurring non-canonical di-alpha-amino acids were converted into new
      di-N-carboxyanhydride (di-NCA) monomers in reasonable yields with high purity.
      Five different di-NCAs were separately copolymerized with tert-butyl-l-glutamate
      NCA to obtain covalently crosslinked copolypeptides capable of forming hydrogels
      with varying crosslinker density. Comparison of hydrogel properties with residue
      structure revealed that different di-alpha-amino acids were not equivalent in
      crosslink formation. Notably, l-cystine was found to produce significantly weaker
      hydrogels compared to l-homocystine, l-cystathionine, and l-lanthionine,
      suggesting that l-cystine may be a sub-optimal choice of di-alpha-amino acid for
      preparation of copolypeptide networks. The di-alpha-amino acid crosslinkers also
      provided different chemical stability, where disulfide crosslinks were readily
      degraded by reduction, and thioether crosslinks were stable against reduction.
      This difference in response may provide a means to fine tune the reduction
      sensitivity of polypeptide biomaterial networks.

PMID- 30221466
TI  - Unappreciated role of low-density lipoprotein receptor-related protein 1 in
      pancreatic beta cells: Multiple roles of low-density lipoprotein receptor-related
      protein 1 in glucose and lipid metabolism.

PMID- 30221467
TI  - Role of social cognition in post-traumatic stress disorder: A review and meta
      analysis.
AB  - Social functioning is a key component of recovery after a potentially traumatic
      experience, and the buffering role of the social support in trauma resilience and
      recovery has been very well documented. Factors contributing to resilience and
      recovery are notable because although most people will experience a traumatic
      event during their lifetimes, only 6% to 10% are diagnosed with post-traumatic
      stress disorder (PTSD). The relationship between an individual and their social
      environment is determined both by the quality of the social environment itself,
      and by the individual's perception and understanding of information conveyed by
      the other people around them. However, little research has considered the
      contribution of these internal social cognitive processes to PTSD risk or
      resilience. The current review draws on the existing literature on social
      cognitive functioning in trauma exposure and PTSD, identifying key questions and
      themes for future research. We utilized a meta-analytic approach to assess the
      evidence for alterations in social cognition in PTSD, finding a consistent large
      deficit in social cognitive performance in PTSD groups relative to trauma-exposed
      and healthy controls. We then reviewed the literature on the interaction of genes
      and the social environment, supporting the hypothesis that social cognitive
      deficits are a preexisting risk factor for PTSD. Finally, we reviewed relevant
      neuroimaging findings, which suggest that alterations in social cognition affect
      the perception of threat cues in PTSD. Overall, research on social cognition and
      PTSD is still emerging, but existing findings suggest this is an important and
      understudied area for the understanding of PTSD.

PMID- 30221468
TI  - Antitrypanosomatid Pharmacomodulation at Position 3 of the 8-Nitroquinolin-2(1H)
      one Scaffold Using Palladium-Catalysed Cross-Coupling Reactions.
AB  - An antikinetoplastid pharmacomodulation study at position 3 of the recently
      described hit molecule 3-bromo-8-nitroquinolin-2(1H)-one was conducted. Twenty
      four derivatives were synthesised using the Suzuki-Miyaura cross-coupling
      reaction and evaluated in vitro on both Leishmania infantum axenic amastigotes
      and Trypanosoma brucei brucei trypomastigotes. Introduction of a para
      carboxyphenyl group at position 3 of the scaffold led to the selective
      antitrypanosomal hit molecule 3-(4-carboxyphenyl)-8-nitroquinolin-2(1H)-one (21)
      with a lower reduction potential (-0.56 V) than the initial hit (-0.45 V).
      Compound 21 displays micromolar antitrypanosomal activity (IC50 =1.5 MUm) and low
      cytotoxicity on the human HepG2 cell line (CC50 =120 MUm), having a higher
      selectivity index (SI=80) than the reference drug eflornithine. Contrary to
      results previously obtained in this series, hit compound 21 is inactive toward L.
      infantum and is not efficiently bioactivated by T. brucei brucei type I
      nitroreductase, which suggests the existence of an alternative mechanism of
      action.

PMID- 30221469
TI  - Paternally inherited WT1 mutation plus uniparental disomy of 11p may be an
      essential mechanism for development of WT1-mutated familial Wilms tumor.

PMID- 30221471
TI  - Systems genetics of sensation seeking.
AB  - Sensation seeking is a multifaceted, heritable trait which predicts the
      development of substance use and abuse in humans; similar phenomena have been
      observed in rodents. Genetic correlations among sensation seeking and substance
      use indicate shared biological mechanisms, but the genes and networks underlying
      these relationships remain elusive. Here, we used a systems genetics approach in
      the BXD recombinant inbred mouse panel to identify shared genetic mechanisms
      underlying substance use and preference for sensory stimuli, an intermediate
      phenotype of sensation seeking. Using the operant sensation seeking (OSS)
      paradigm, we quantified preference for sensory stimuli in 120 male and 127 female
      mice from 62 BXD strains and the C57BL/6J and DBA/2J founder strains. We used
      relative preference for the active and inactive levers to dissociate preference
      for sensory stimuli from locomotion and exploration phenotypes. We identified
      genomic regions on chromosome 4 (155.236-155.742 Mb) and chromosome 13 (72.969
      89.423 Mb) associated with distinct behavioral components of OSS. Using publicly
      available behavioral data and mRNA expression data from brain regions involved in
      reward processing, we identified (a) genes within these behavioral QTL exhibiting
      genome-wide significant cis-eQTL and (b) genetic correlations among OSS
      phenotypes, ethanol phenotypes and mRNA expression. From these analyses, we
      nominated positional candidates for behavioral QTL associated with distinct OSS
      phenotypes including Gnb1 and Mef2c. Genetic covariation of Gnb1 expression,
      preference for sensory stimuli and multiple ethanol phenotypes suggest that
      heritable variation in Gnb1 expression in reward circuitry partially underlies
      the widely reported relationship between sensation seeking and substance use.

PMID- 30221470
TI  - Chinese expert consensus on diagnosis and management of acquired respiratory
      digestive tract fistulas.
AB  - Acquired respiratory-digestive tract fistulas occur with abnormal communication
      between the airways and digestive tract, causing the interflow of gas and liquid.
      Despite advances in surgical methods and the development of multimodal therapy in
      recent years, patients with acquired respiratory-digestive tract fistulas
      continue to exhibit unfavorable clinical outcomes. Therefore, in order to guide
      clinical practice in China, the Respiratory and Cancer Intervention Alliance of
      the Beijing Health Promotion Association organized a group of experienced experts
      in the field to develop this consensus document. Based on a study of clinical
      application and expert experience in the diagnosis and management of acquired
      respiratory-digestive tract fistulas at home and abroad, an Expert Consensus was
      developed. The panelists recruited comprised experts in pulmonology, oncology,
      thoracic surgery, interventional radiology, and gastroenterology. PubMed, Chinese
      Biology Abstract, Chinese Academic Journal, and Wanfang databases were used to
      identify relevant articles. The guidelines address etiology, classification,
      pathogenesis, diagnosis and management of acquired respiratory-digestive tract
      fistulas. The statements on treatment focus on the indications for different
      procedures, technical aspects, and preprocedural, post-procedural and
      complication management. The proposed guidelines for the diagnosis and management
      of acquired respiratory-digestive tract fistulas are the first to be published by
      Chinese experts. These guidelines provide an in-depth review of the current
      evidence and standard of diagnosis and management.

PMID- 30221472
TI  - Inhibiting Pneumococcal Surface Antigen A (PsaA) with Small Molecules Discovered
      through Virtual Screening: Steps toward Validating a Potential Target for
      Streptococcus pneumoniae.
AB  - The pneumococcal surface antigen A (PsaA) metal transporter protein provides
      manganese to bacterial cells. The X-ray crystal structures of PsaA, in both
      closed (Mn bound) and open (metal free) conformations, were explored with virtual
      screening to identify potential inhibitors of manganese transport. We pursued
      three strategies for inhibition: i) targeting a cavity close to the bound Mn to
      keep the metal in place; ii) targeting the metal-free Mn site to prevent metal
      uptake; and iii) targeting a potentially druggable allosteric site involving
      loops that translate between the conformations. Tiered assays were used to test
      the resulting 170 acquired hits: i) assay 1 tested the compounds' growth
      inhibition of the TIGR4 S. pneumoniae strain (DeltaPsaA mutant control), yielding
      80 compounds (MIC<=250 MUm); ii) assay 2 tested if the addition of 20 MUm Mn to
      inhibited cell cultures restored growth, yielding 21 compounds; and iii) assay 3
      confirmed that the restored bacterial growth was Mn concentration dependent, as
      was the restoration of DeltaPsaA growth, yielding 12 compounds with MICs of 125
      MUm or greater. It may be possible for a small molecule to inhibit PsaA, but we
      have not yet identified a compound with exemplary properties.

PMID- 30221474
TI  - In Situ Synchrotron X-Ray Diffraction Characterization of Corrosion Products of a
      Ti-Based Metallic Glass for Implant Applications.
AB  - Ti-based bulk metallic glasses are under consideration for implants due to their
      high yield strength and biocompatibility. In this work, in situ synchrotron X-ray
      diffraction (XRD) is used to investigate the corrosion products formed from
      corrosion of Ti40 Zr10 Cu34 Pd14 Sn2 bulk metallic glass in artificial corrosion
      pits in physiological saline (NaCl). It is found that Pd nanoparticles form in
      the interior of the pits during electrochemical dissolution. At a low pit growth
      potential, the change in lattice parameter of the Pd nanoparticles is consistent
      with the formation of palladium hydride. In addition, a salt layer very close to
      the dissolving interface is found to contain CuCl, PdCl2 , ZrOCl2 ?8H2 O, Cu, Cu2
      O, and several unidentified phases. The formation of Pd nanoparticles (16 +/- 10
      nm at 0.7 V vs Ag/AgCl) containing small amounts of the other alloying elements
      is confirmed by transmission electron microscopy. The addition of albumin and/or
      H2 O2 does not significantly influence the nature of the corrosion products. When
      considering the biological compatibility of the alloy, the biological reactivity
      of the corrosion products identified should be explored.

PMID- 30221473
TI  - Metformin blocks MYC protein synthesis in colorectal cancer via mTOR-4EBP-eIF4E
      and MNK1-eIF4G-eIF4E signaling.
AB  - The antidiabetic drug metformin has been associated with reduced colorectal
      cancer (CRC) risk and improved prognosis of CRC patients. However, the detailed
      mechanisms underlying such beneficial effects remain unknown. In this study, we
      aimed to evaluate metformin activity in CRC models and unveil the underlying
      molecular mechanisms. We showed that metformin inhibits CRC cell proliferation by
      arresting cells in the G1 phase of the cell cycle and dramatically reduces colony
      formation of CRC cells. We discovered that metformin causes a robust reduction of
      MYC protein level. Through the use of luciferase assay and coincubation with
      either protein synthesis or proteasome inhibitors, we demonstrated that
      regulation of MYC by metformin is independent of the proteasome and 3' UTR
      mediated regulation, but depends on protein synthesis. Data from polysome
      profiling and ribopuromycylation assays showed that metformin induced widespread
      inhibition of protein synthesis. Repression of protein synthesis by metformin
      preferentially affects cell cycle-associated proteins, by altering signaling
      through the mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E axes. The inhibition of MYC
      protein synthesis may underlie metformin's beneficial effects on CRC risk and
      prognosis.

PMID- 30221476
TI  - Using Questions to Enhance Rheumatology Education.
AB  - Meeting the increased demand for rheumatology care in the future will require
      changing the way rheumatology is taught. Enhancing rheumatology education may
      encourage more trainees to pursue rheumatology careers and improve knowledge
      about musculoskeletal conditions for primary care providers. However, the
      inherent uncertainty that surrounds the etiology, diagnosis, and treatment of
      many rheumatic diseases presents a unique challenge to rheumatology education and
      demands a distinct approach. By mastering the art of questioning, faculty can
      improve a learner's ability to understand and remember the material, apply
      knowledge in new settings, overcome cognitive biases, support an environment of
      inquiry, and develop metacognition, even under uncertainty. Trainees should also
      learn the craft of asking questions as a method of studying, a practice that
      stimulates curiosity, and a tool that will help them become life-long, self
      directed learners. In this guide, we present the evidence behind the power of
      questions, provide a model for the best use of questions in various teaching
      venues, and recommend specific techniques for effective questioning. This article
      is protected by copyright. All rights reserved.

PMID- 30221475
TI  - Oncogenic microRNA signature for early diagnosis of cervical intraepithelial
      neoplasia and cancer.
AB  - Cervical cancer is one of the leading causes of cancer death in women globally,
      despite the widespread use of cytology/human papillomavirus (HPV) screening. In
      the present study, we aimed to identify the potential role of microRNA (miRNA) as
      a diagnostic biomarker in the detection of cervical pre-malignant lesions and
      cancer. In total, we recruited 582 patients with cervical diseases and 145
      control individuals. The expression levels of six miRNAs (miR-20a, miR-92a, miR
      141, miR-183*, miR-210 and miR-944) were found to be significantly up-regulated
      in cervical cancer and pre-malignant lesions compared to normal cervical samples,
      indicating that they are oncogenic miRNAs. Receiver operating characteristic
      curve analysis showed that these six miRNAs can be used to distinguish patients
      with cervical pre-malignant lesions or cancer from normal individuals and they
      also had a good predictive performance, particularly in cervical lesions.
      Combined use of these six miRNAs further enhanced the diagnostic accuracy over
      any single miRNA marker, with an area under the curve of 0.998, 0.996 and 0.959,
      a diagnostic sensitivity of 97.9%, 97.2% and 91.4%, and a specificity of 98.6%,
      96.6% and 87.6% for low-grade lesions, high-grade lesions and cancer,
      respectively. This six oncogenic miRNA signature may be suitable for use as
      diagnostic marker for cervical pre-malignant lesions and cancer in the near
      future.

PMID- 30221477
TI  - A transcriptomics model of estrogen action in the ovine fetal hypothalamus:
      evidence for estrogenic effects of ICI 182,780.
AB  - Estradiol plays a critical role in stimulating the fetal hypothalamus-pituitary
      adrenal axis at the end of gestation. Estradiol action is mediated through
      nuclear and membrane receptors that can be modulated by ICI 182,780, a pure
      antiestrogen compound. The objective of this study was to evaluate the
      transcriptomic profile of estradiol and ICI 182,780, testing the hypothesis that
      ICI 182,780 antagonizes the action of estradiol in the fetal hypothalamus.
      Chronically catheterized ovine fetuses were infused for 48 h with: vehicle
      (Control, n = 6), 17beta-estradiol 500 MUg/kg/day (Estradiol, n = 4), ICI 182,780
      5 MUg/kg/day (ICI 5 MUg, n = 4) and ICI 182,780 5 mg/kg/day (ICI 5 mg, n = 5).
      Fetal hypothalami were collected afterward, and gene expression was measured
      through microarray. Statistical analysis of transcriptomic data was performed
      with Bioconductor-R and Cytoscape software. Unexpectedly, 35% and 15.5% of the
      upregulated differentially expressed genes (DEG) by Estradiol significantly
      overlapped (P < 0.05) with upregulated DEG by ICI 5 mg and ICI 5 MUg,
      respectively. For the downregulated DEG, these percentages were 29.9% and 15.5%,
      respectively. There was almost no overlap for DEG following opposite directions
      between Estradiol and ICI ICI 5 mg or ICI 5 MUg. Furthermore, most of the genes
      in the estrogen signaling pathway - after activation of the epidermal growth
      factor receptor - followed the same direction in Estradiol, ICI 5 MUg or ICI 5 mg
      compared to Control. In conclusion, estradiol and ICI 182,780 have estrogenic
      genomic effects in the developing brain, suggesting the possibility that the
      major action of estradiol on the fetal hypothalamus involves another receptor
      system rather than estrogen receptors.

PMID- 30221478
TI  - The prevalence of sarcopenia and relationships between muscle and bone in ageing
      West-African Gambian men and women.
AB  - BACKGROUND: The rapidly rising ageing population in low and middle-income
      countries (LMIC) will lead to a concurrent increase in musculoskeletal diseases.
      Sarcopenia is a disease caused by progressive loss of skeletal muscle mass and
      strength, leading to adverse outcomes including frailty, falls, fractures, and
      premature mortality. We investigated the prevalence of sarcopenia, assessed the
      suitability of current diagnostic guidelines and explored muscle-bone
      relationships in ageing men and women from rural Gambia. METHODS: A total of 249
      women and 239 men aged 40-75+ years were recruited. Body composition was measured
      using dual energy X-ray absorptiometry. Comparisons of the Foundations for the
      National Institutes of Health (FNIH) and European Working Group On Sarcopenia
      (EWGSOP) definitions of sarcopenia to define prevalence and to identify poor
      physical capability were determined. Functional ability was assessed by jumping
      mechanography to calculate lower limb muscle force and power; grip strength was
      assessed by a hand dynamometer. Peripheral quantitative computed tomography was
      used to assess muscle-bone relationships. RESULTS: The prevalence of sarcopenia
      in Gambian men and women significantly varied depending on the definition used;
      in men 20% and 19% and in women 45% and 10% for FNIH and EWGSOP, respectively.
      The FNIH appendicular lean mass cut-off had greatest sensitivity and specificity
      in identifying low functional ability in Gambian adults. Muscle force was
      positively associated with measures of tibial bone size, strength, and mineral
      content. CONCLUSIONS: The variation in the prevalence of sarcopenia depends on
      the definition used and highlights the importance of measuring functional
      capability across ethnic populations.

PMID- 30221480
TI  - Preparation and Reactivity of Biomass-Derived Dihydro-Dioxins.
AB  - The depolymerization of the biopolymer lignin can give pure aromatic monomers but
      selective catalytic approaches remain scarce. Here, an approach was rerouted to
      deliver an unusual phenolic monomer. This monomer's instability proved
      challenging, but a degradation study identified strategies to overcome this.
      Heterocycles and a useful synthetic intermediate were prepared. The range of
      aromatics available from the beta-O-4 unit in lignin was extended.

PMID- 30221479
TI  - Repeatability of Dixon magnetic resonance imaging and magnetic resonance
      spectroscopy for quantitative muscle fat assessments in the thigh.
AB  - BACKGROUND: Changes in muscle fat composition as for example observed in
      sarcopenia or muscular dystrophy affect physical performance and muscular
      function, like strength and power. The purpose of the present study is to measure
      the repeatability of Dixon magnetic resonance imaging (MRI) for assessing muscle
      volume and fat in the thigh. Furthermore, repeatability of magnetic resonance
      spectroscopy (MRS) for assessing muscle fat is determined. METHODS: A prototype 6
      point Dixon MRI method was used to measure muscle volume and muscle proton
      density fat fraction (PDFF) in the left thigh. PDFF was measured in musculus
      semitendinosus of the left thigh with a T2-corrected multi-echo MRS method. For
      the determination of short-term repeatability (consecutive examinations), the
      root mean square coefficients of variation of Dixon MRI and MRS data of 23 young
      and healthy (29 +/- 5 years) and 24 elderly men with sarcopenia (78 +/- 5 years)
      were calculated. For the estimation of the long-term repeatability (13 weeks
      between examinations), the root mean square coefficients of variation of MRI data
      of seven young and healthy (31 +/- 7 years) and 23 elderly sarcopenic men (76 +/-
      5 years) were calculated. Long-term repeatability of MRS was not determined.
      RESULTS: Short-term errors of Dixon MRI volume measurement were between 1.2% and
      1.5%, between 2.1% and 1.6% for Dixon MRI PDFF measurement, and between 9.0% and
      15.3% for MRS. Because of the high short-term repeatability errors of MRS, long
      term errors were not determined. Long-term errors of MRI volume measurement were
      between 1.9% and 4.0% and of Dixon MRI PDFF measurement between 2.1% and 4.2%.
      CONCLUSIONS: The high degree of repeatability of volume and PDFF Dixon MRI
      supports its use to predict future mobility impairment and measures the success
      of therapeutic interventions, for example, in sarcopenia in aging populations and
      muscular dystrophy. Because of possible inhomogeneity of fat infiltration in
      muscle tissue, the application of MRS for PDFF measurements in muscle is more
      problematic because this may result in high repeatability errors. In addition,
      the tissue composition within the MRS voxel may not be representative for the
      whole muscle.

PMID- 30221481
TI  - HSP90 as a global genetic modifier for male genital morphology in Drosophila
      melanogaster.
AB  - The molecular chaperone protein HSP90 has been proposed to modulate genotype
      phenotype relationship in a broad range of organisms. We explore the proposed
      genetic modifier effect of HSP90 through a genomewide analysis. Here, we show
      that HSP90 functions as a genetic modifier of genital morphology in Drosophila
      melanogaster. We identified a large number of single-nucleotide polymorphisms
      (SNPs) with an HSP90-dependent effect by using genome wide association analysis.
      We classified the SNPs into the ones under capacitance effect (smaller allelic
      effect under HSP90 inhibition) or the ones under potentiation effect (larger
      allelic effect under HSP90 inhibition). Although the majority of SNPs are under
      capacitance, there are a large number of SNPs under potentiation. This
      observation provides support for a model in which Hsp90 is not described
      exclusively as a "genetic capacitor," but is described more broadly as a "genetic
      modifier." Because the majority of the candidate genes estimated from SNPs with
      an HSP90-dependent effect in the current study has never been reported to
      interact with HSP90 directly, the global genetic modifier effect of HSP90 may be
      exhibited through epistatic interactions in gene regulatory networks.

PMID- 30221482
TI  - Repetitive knee bending and synovitis in people at risk and with knee
      osteoarthritis: Data from the FNIH Osteoarthritis Biomarkers Consortium.
AB  - OBJECTIVE: To investigate associations between engagement in knee bending (stair
      climbing, kneeling, squatting, heavy lifting, getting in/out of a squatting
      position) and synovitis prevalence on non-contrast magnetic resonance imaging
      (MRI) in people at risk and with knee osteoarthritis (OA). METHODS: We included
      baseline data from 594 participants (age: 61.5 +/- 8.9 years; 61% Kellgren
      Lawrence grade >=2; 59% female; body mass index: 30.7 +/- 4.8 kg/m2 ) of the
      Osteoarthritis Biomarker Consortium Foundation for the National Institutes of
      Health project. Knee bending activities were queried by standard questionnaire
      and severity of Hoffa-synovitis and effusion-synovitis (surrogate outcomes of
      synovitis) graded utilizing the MRI OsteoArthritis Knee Scoring system. Logistic
      regression was used, unadjusted and adjusted for metabolic syndrome, physical
      activity level and sex. A grade >=1 defined synovitis prevalence, with a grade
      >=2 cut-off implemented in sensitivity analyses. RESULTS: The prevalence of grade
      >=1 Hoffa-synovitis and effusion-synovitis equaled 59% (n=353) and 62% (n=366),
      respectively. Adjusted for confounders, kneeling for >=30 minutes during a single
      day was associated with grade >=1 Hoffa-synovitis prevalence (odds ratio (OR)
      (95% confidence interval (CI)): 1.65 (1.11, 2.47)). Participants engaging in this
      activity one day or less per week had greater odds for prevalent Hoffa-synovitis,
      than those who did not perform the activity (OR (95% CI):1.88 (1.11, 3.18)). No
      other significant associations were found. Sensitivity analyses yielded similar
      findings. CONCLUSIONS: In this selected sample with a preponderance of grade >=1
      Hoffa- and/or effusion-synovitis on non-contrast MRI, only prolonged kneeling
      associated with Hoffa-synovitis prevalence. Replication in other samples is
      warranted. This article is protected by copyright. All rights reserved.

PMID- 30221483
TI  - Biopsy-Proven Small-Fiber Neuropathy in Primary Sjogren's Syndrome:Neuropathic
      Pain Characteristics, Autoantibody Findings, and Histopathological Features.
AB  - INTRODUCTION: Painful small-fiber neuropathies (SFN) in primary Sjogren's
      syndrome (SS) may present as pure or mixed with concurrent large-fiber
      involvement. SFN can be diagnosed by punch skin biopsies, which identifies
      decreased intra-epidermal nerve-fiber density (IENFD) of unmyelinated nerves.
      METHODS: We compared 23 consecutively evaluated SS patients with pure and mixed
      SFN versus 98 without. We distinguished between markers of dorsal root ganglia
      (DRG) degeneration (decreased IENFD proximal thigh versus distal leg) versus
      axonal degeneration (decreased IENFD distal leg versus proximal thigh). RESULTS:
      There were no differences in pain intensity, quality, and treatment
      characteristics comparing 13 pure SFN versus 10 mixed SFN patients. Ten SFN
      patients (~45%) had neuropathic pain preceding sicca symptoms. Opioid analgesics
      were prescribed to ~45% SFN patients. When compared to 98 non-SFN patients, the
      23 SFN patients had increased frequency of male sex (30% versus 9%, p<0.01),
      decreased frequency of anti-Ro52 (p=0.01) and anti-Ro60 antibodies (p=0.01),
      rheumatoid factor (p<0.01), and polyclonal gammopathy (p<0.01). Eleven patients
      had stocking-and-glove pain, and 12 patients had non-stocking-and-glove pain.
      Skin biopsy disclosed patterns of axonal (16 patients) and DRG injury (7
      patients). CONCLUSION: SS SFN had increased frequency of male sex, decreased
      frequency of multiple antibodies, were frequently treated with opioid analgesics,
      and could present with non-stocking-and-glove pain. Distinguishing between DRG
      versus axonal injury is significant, especially given that mechanisms targeting
      the DRG may result in irreversible neuronal cell death. Altogether, these
      findings highlight clinical, autoantibody, and pathological features that can
      help to define mechanisms and treatment strategies. This article is protected by
      copyright. All rights reserved.

PMID- 30221484
TI  - Concurrent change in quadriceps strength and physical function over 5 years in
      The Multicenter Osteoarthritis Study.
AB  - OBJECTIVE: Quadriceps weakness, associated with functional limitations, is a
      target of treatment of knee osteoarthritis (OA). Limited data exist on modest
      strength increases and improvements in function. We evaluated concurrent change
      in strength and physical function over 5 years. METHODS: Using subjects from the
      Multicenter Osteoarthritis (MOST) study, we excluded those with knee replacement
      after baseline. A 3-category variable defined whether, at 5 years, knee extensor
      strength increased, decreased or remained within 15% of baseline, a clinically
      important cutoff. OUTCOMES: Five-Times Sit-to-Stand-Test, 20-Meter Walk Test,
      WOMAC Physical Function Score, and 3 individual physical functions from WOMAC:
      arising from a chair, going up stairs and getting on/off toilet. Linear and
      logistic models, stratified by sex, evaluated associations between change in
      strength and change in physical function over 5 years. To compare weaker vs.
      stronger women, we stratified analyses at 56Nm baseline strength. RESULTS: Among
      1534 participants (60.6% women), 22% of men and 30% of women increased strength
      by at least 15% at 5 years. Compared with women whose strength did not change,
      women whose strength increased had improved chair stand performance (OR=2.27, 95%
      CI 1.56, 3.30) but no improvements in other functions. In men, increase in
      strength was not associated with significant improvement in physical function.
      20% or 30% change showed similar results. CONCLUSION: Modest improvement in
      quadriceps strength was associated with improved chair stand performance in
      women, but not in men. Most functions did not improve with an increase in
      strength, and may require targeted interventions to improve functional status.
      This article is protected by copyright. All rights reserved.

PMID- 30221485
TI  - Low Persistence Rates in Rheumatoid Arthritis Patients Treated with Triple
      Therapy are Attributed to Adverse Drug Events Associated with Sulfasalazine.
AB  - OBJECTIVE: Combination treatments for rheumatoid arthritis (RA) patients with
      inadequate response to methotrexate (MTX) alone include the addition of tumor
      necrosis factor inhibitors (TNFi) or the addition of sulfasalazine (SSZ) and
      hydroxychloroquine (HCQ) to MTX (triple therapy, TT). We compared persistence and
      adherence rates between these two combination therapies in US Veterans and report
      the reasons for discontinuation of combination treatment in these groups.
      METHODS: Using Veteran's Affairs (VA) clinical and administrative data from 2006
      to 2012, veterans with RA escalating treatment from MTX to MTX-TNFi or triple
      therapy were examined for a 12-month period after combination initiation.
      Persistence was defined as treatment without a >=90-day gap in therapy. Adherence
      was calculated using proportion of days covered (PDC) >=80% at 12 months.
      Matching weights-adjusted models were applied to more closely mimic randomization
      in this study. The reasons that patients discontinued their combination regimens
      were identified by chart abstraction. RESULTS: Full persistence at one year was
      45% in the MTX-TNFi patients (n=2,125) and 18% in the triple therapy patients
      (n=171) (p<0.001). Adherence was higher for the MTX-TNFi group (26%) than the
      triple therapy group (11%) (p<0.0001). The triple therapy group was associated
      with significantly more treatment discontinuation, which was most often due to
      adverse drug events (ADE) from SSZ. CONCLUSION: Differences in persistence and
      adherence between the MTX-TNFi and triple therapy groups appear to be primarily
      related to ADE that were most often attributed to SSZ. This article is protected
      by copyright. All rights reserved.

PMID- 30221486
TI  - Identification of the novel HLA-A*23:91N allele in a Saudi individual.
AB  - HLA-A*23:91N differs from HLA-A*23:01:01 by a single-nucleotide substitution (G 
      > A) at position 369.

PMID- 30221487
TI  - The incidence, clinical manifestations and severity of Juvenile Idiopathic
      Arthritis among Maori and Pacific Island children.
AB  - OBJECTIVE: To describe the incidence, demographics, diagnostic clinical
      manifestations and severity of Juvenile Idiopathic Arthritis (JIA) in Maori and
      Pacific Island children compared to European children. METHOD: A chart review was
      conducted of all children with JIA seen by Auckland Pediatric and Rheumatology
      services between 2000 and 2015. Demographic data and diagnostic clinical
      manifestations including poor prognostic features were collated. The incidence,
      diagnostic clinical manifestations and severity of JIA were determined and
      compared between ethnic groups, in particular Maori and Pacific and European
      children. RESULTS: The overall incidence in a New Zealand cohort of children with
      JIA was 5.1/100,000 per year which was significantly higher among European
      children (7.2/100,000 per year) compared to all other ethnic groups. Poor
      prognostic features at diagnosis were present in 36% with significantly more
      Maori and Pacific Island children presenting with poor prognostic features
      compared to European children (58% vs 27%, p=0.0001). Maori and Pacific children
      had significantly more poor prognostic features per child associated with JIA
      (1.10 vs 0.37, p=<0.0001), oligoarticular and polyarticular disease (1.28 vs
      0.40, p<0.0001), which was independent of socio-economic status (SES).
      Significant features included cervical involvement (25% vs 9%, 0.03), erosive
      changes (22% vs 8%, p=0.05), joint space narrowing (13% vs 2%, p=0.02) and
      polyarticular rheumatoid factor positive disease (47% vs 14%, p=0.01).
      CONCLUSION: Maori and Pacific Island children were more likely to present with
      poor prognostic features at diagnosis although the incidence of JIA was
      demonstrated to be significantly higher among European children compared to all
      ethnic groups. This article is protected by copyright. All rights reserved.

PMID- 30221489
TI  - Use of wearable activity trackers to improve physical activity behavior in
      rheumatic and musculoskeletal diseases: A systematic review and meta-analysis.
AB  - OBJECTIVE: Wearable activity trackers (WATs) could be a promising strategy to
      improve physical activity (PA) in patients with rheumatic and musculoskeletal
      diseases (RMDs). The aim was to assess the adherence and effectiveness of WATs to
      increase PA levels in RMDs. METHODS: A systematic review was performed to
      identify all cohorts and controlled trials evaluating WATs in RMDs, published
      between 2000 and 2018, by searching MEDLINE, EMBASE, PsycINFO and Cochrane. Data
      collected pertained to (a) adherence, (b) effectiveness on PA or (c)
      effectiveness on symptoms (pain, function, quality of life or fatigue). Meta
      analyses were performed with a random effect model. RESULTS: Of 2378 references,
      17 studies were included with a total of 1588 patients; 8 studies (47%) in
      osteoarthritis, 5 (29%) in low back pain and 3 (18%) in inflammatory arthritis.
      Adherence assessed in 4 studies was high (weighted mean time worn: 92.7%
      (standard deviation 4.6%). A significant increase in PA was noted (mean
      difference 1520 steps, 95% confidence interval [580 - 2460], I2=77% or 16 minutes
      [2 - 29] of moderate to vigorous PA, I2=0%). A significant increase in pain was
      found for long interventions (>8 weeks) (standardized mean difference 0.25 [0.07,
      0.43], I2= 0%). CONCLUSION: WATs in RMDs had a high short-term adherence with a
      significant increase in number of steps and time spent in moderate to vigorous PA
      though pain should be monitored. WATs may be an effective option to increase PA
      in this at risk population. Registered in PROSPERO: CRD42018083532. This article
      is protected by copyright. All rights reserved.

PMID- 30221490
TI  - Patient Perspectives on Intravenous Biologics for Rheumatologic Disease.
AB  - OBJECTIVE: Two surveys were conducted with patients with rheumatologic diseases
      to evaluate perceptions of different routes of administration (intravenous [IV]
      or subcutaneous [SC]) for biologic therapy. METHODS: In Survey I, patient
      preferences towards biologic treatment were evaluated at a rheumatology practice
      in Buffalo, New York. In Survey II, Canadian patients enrolled in the
      BioAdvance(r) patient support program and scheduled to receive IV biologic
      therapy were asked about their opinions of IV treatment. RESULTS: In Survey I,
      243 rheumatology patients participated. Median patient age was 60 years; 76% were
      female and 44% were bionaive. Among bionaive patients, the majority (56%) were
      open to either SC or IV treatment; bionaive women were more likely than men to
      express a preference for the route of administration. In Survey II, 1,598
      BioAdvance(r) patients (including 306 rheumatology patients) completed the full
      survey. Among the rheumatology patients, the median age was 49 years, 58% were
      female, and 61% had not previously used biologics before enrolling in the
      BioAdvance(r) program. The median rating of IV favorability (on a 10-point scale,
      with higher numbers indicating increased favorability) recalled by rheumatology
      patients was five prior to their first program infusion, and increased to nine
      after multiple treatment infusions. CONCLUSIONS: These survey results indicate
      that RA patients are generally open to IV treatment and express high satisfaction
      with IV therapy. Additional patient and provider education may improve shared
      decision-making regarding biologic therapy administration options. This article
      is protected by copyright. All rights reserved.

PMID- 30221488
TI  - Trichoderma gamsii affected herbivore feeding behaviour on Arabidopsis thaliana
      by modifying the leaf metabolome and phytohormones.
AB  - Plants can re-programme their transcriptome, proteome and metabolome to deal with
      environmental and biotic stress. It has been shown that the rhizosphere
      microbiome has influence on the plant metabolome and on herbivore behaviour. In
      the present study, Trichoderma gamsii was isolated from Arabidopsis thaliana
      rhizosphere soil. The inoculation of roots of Arabidopsis thaliana with T. gamsii
      significantly inhibited the feeding behaviour of Trichoplusia ni and affected the
      metabolome as well as the content of phytohormones in Arabidopsis leaves. T.
      gamsii-treated plant leaves had higher levels of amino acids and lower
      concentrations of sugars. In addition, T. gamsii-treated plant leaves had more
      abscisic acid (ABA) and lower levels of salicylic acid (SA) and indole-3-acetic
      acid (IAA) in comparison with the untreated plants. Furthermore, the inoculation
      with T. gamsii on different signalling mutants showed that the induction of
      defences were SA-dependent. These findings indicate that T. gamsii has potential
      as a new type of biocontrol agent to promote plant repellence to insect attacks.

PMID- 30221492
TI  - European Society of Cardiology 2018.
AB  - Martin J. Kurian, Peter J. Rentzepis, Ann M. Carracher, and Kelly L. Close are of
      Close Concerns (http://www.closeconcerns.com), a healthcare information company
      focused exclusively on diabetes and obesity care. Close Concerns publishes Closer
      Look, a periodical that brings together news and insights in these areas. Each
      month, the Journal of Diabetes includes this News feature, in which Kurian,
      Rentzepis, Carracher, and Close review the latest developments relevant to
      researchers and clinicians.

PMID- 30221491
TI  - The novel HLA-B allele, HLA-B*50:31, was identified by sequencing genomic DNA.
AB  - The novel HLA-B allele, HLA-B*50:31, was identified by sequencing genomic DNA.

PMID- 30221493
TI  - A novel real-time computational framework for detecting catheters and rigid
      guidewires in cardiac catheterization procedures.
AB  - PURPOSE: Catheters and guidewires are used extensively in cardiac catheterization
      procedures such as heart arrhythmia treatment (ablation), angioplasty, and
      congenital heart disease treatment. Detecting their positions in fluoroscopic X
      ray images is important for several clinical applications, for example, motion
      compensation, coregistration between 2D and 3D imaging modalities, and 3D object
      reconstruction. METHODS: For the generalized framework, a multiscale vessel
      enhancement filter is first used to enhance the visibility of wire-like
      structures in the X-ray images. After applying adaptive binarization method, the
      centerlines of wire-like objects were extracted. Finally, the catheters and
      guidewires were detected as a smooth path which is reconstructed from centerlines
      of target wire-like objects. In order to classify electrode catheters which are
      mainly used in electrophysiology procedures, additional steps were proposed.
      First, a blob detection method, which is embedded in vessel enhancement filter
      with no additional computational cost, localizes electrode positions on
      catheters. Then the type of electrode catheters can be recognized by detecting
      the number of electrodes and also the shape created by a series of electrodes.
      Furthermore, for detecting guiding catheters or guidewires, a localized machine
      learning algorithm is added into the framework to distinguish between target wire
      objects and other wire-like artifacts. The proposed framework were tested on
      total 10,624 images which are from 102 image sequences acquired from 63 clinical
      cases. RESULTS: Detection errors for the coronary sinus (CS) catheter, lasso
      catheter ring and lasso catheter body are 0.56 +/- 0.28 mm, 0.64 +/- 0.36 mm, and
      0.66 +/- 0.32 mm, respectively, as well as success rates of 91.4%, 86.3%, and
      84.8% were achieved. Detection errors for guidewires and guiding catheters are
      0.62 +/- 0.48 mm and success rates are 83.5%. CONCLUSION: The proposed
      computational framework do not require any user interaction or prior models and
      it can detect multiple catheters or guidewires simultaneously and in real-time.
      The accuracy of the proposed framework is sub-mm and the methods are robust
      toward low-dose X-ray fluoroscopic images, which are mainly used during
      procedures to maintain low radiation dose.

PMID- 30221494
TI  - miR-34a/BCL-2 signaling axis contributes to apoptosis in MPP+ -induced SH-SY5Y
      cells.
AB  - BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder which mainly
      affects the elderly population of various societies. The main hallmark of this
      disease is the loss of dopaminergic (DA) neurons. So far, numerous studies have
      implied the role of microRNAs in fine-tuning cellular processes including
      apoptosis. Studies have also shown that miR-34a is mainly involved in age-related
      disorders including Alzheimer's disease, and its expression is usually higher in
      the brain sample patients. Furthermore, the key role of miR-34a in the expression
      of BCL-2, and thus, in vitro and in vivo apoptosis has been revealed. miR-34a/BCL
      2 axis is therefore of critical importance in inducing or inhibiting apoptosis.
      METHODS: In this study, human SH-SY5Y cells were treated with MPP+ and the
      expression of miR-34a and BCL2 was assessed. RESULTS: Our results also showed
      that treating human SH-SY5Y neuronal cells using MPP+ to induce oxidative stress
      and apoptosis led to the upregulation of miR-34a, as compared to the nontreated
      control group. Moreover, evaluating the expression level of BCL-2 in these cells
      indicated a contradictory pattern, as compared with miR-34a. It was also revealed
      that the expression of BCL-2 was significantly decreased in MPP+ -treated cells,
      thereby confirming previous studies regarding a new concept. In this study, we
      show that miR-34a/BCL-2 axis is directly correlated with oxidative stress and
      apoptosis in SH-SY5Y cells as a model of DA neurons. CONCLUSION: miR-34a and its
      target gene, BCL-2, play a possible role in the induction of apoptosis in DA
      neurons, and therefore, they have a potential role in the pathogenesis of PD.
      Consequently, the therapeutic potential of miR-34a could be considered in order
      to inhibit the progression of PD.

PMID- 30221495
TI  - Palmoplantar keratoderma Bothnia type with acrokeratoelastoidosis-like features
      due to AQP5 mutations.

PMID- 30221496
TI  - Nanogel Tectonics for Tissue Engineering: Protein Delivery Systems with Nanogel
      Chaperones.
AB  - Amphiphilic polysaccharide self-assembled (SA) nanogels are promising protein
      carriers owing to their chaperone-like activity that allows them to
      nanoencapsulate proteins within their polymer networks. The chaperoning function
      is an important concept that has led to breakthroughs in the development of
      effective protein drug delivery systems by stabilizing formulations and
      controlling the quality of unstable proteins. Recently, nanogel-tectonic
      materials that integrate SA nanogels as building blocks have been designed as new
      hydrogel biomaterials. This article describes recent progress and applications of
      SA nanogel tectonic materials as protein delivery systems for tissue engineering.

PMID- 30221497
TI  - Comprehensive analysis of predictive factors for rapid angiographic stenotic
      progression and restenosis risk in coronary artery disease patients underwent
      percutaneous coronary intervention with drug-eluting stents implantation.
AB  - BACKGROUND: This study aimed to explore the correlation of baseline, procedural,
      and postprocedure characteristics with the risk of rapid angiographic stenotic
      progression (RASP) and restenosis in coronary artery disease (CAD) patients after
      percutaneous coronary intervention (PCI) with drug-eluting stents implantation.
      METHODS: Two hundred fourteen CAD patients underwent PCI with drug-eluting stents
      implantation were consecutively enrolled. Baseline, procedural, and postprocedure
      characteristics of patients were collected for analysis. Coronary angiography was
      performed to evaluate coronary stenosis before PCI and at 12 months after PCI.
      RASP of nontarget lesions and restenosis of stent-implanted target lesions were
      then assessed. RESULTS: 37.8% CAD patients occurred RASP at 12 months after PCI
      and compared to non-RASP group, RASP group presented with increased diabetes
      mellitus (DM) complication, higher concentration of serum uric acid (SUA),
      cardiac troponin I, N-terminal probrain natriuretic peptide, and high sensitive C
      reactive protein (hs-CRP) as well as elevated occurrence of multivessel artery
      lesions. In addition, DM, SUA, hs-CRP, and multivessel artery lesions
      independently predicted high RASP risk. For restenosis, 21.0% patients occurred
      restenosis at 12 months after PCI, and patients in restenosis group presented
      with increased hypertension and DM occurrence, higher concentrations of SUA, LDL
      C, and hs-CRP, as well as longer target lesion and length of stent in surgery
      compared to nonrestenosis group. Also, DM, SUA, LDL-C, hs-CRP, and length of
      target lesion independently predicted increased restenosis risk. CONCLUSION:
      Diabetes mellitus, SUA, and hs-CRP are potential predictive factors for increased
      risk of both RASP and restenosis in CAD patients underwent PCI and drug-eluting
      stents implantation.

PMID- 30221498
TI  - Nectin1 expression is frequently decreased in gastric cancers.
AB  - Gastric cancer (GC) is rich in many different histological types, but how the
      histological pattern is defined remains to be proved. The relation between GC
      histological types and the expression of nectin1, which is one of the cell
      adhesion molecules that composes adherens junction, has not been reported.
      According to a publicly available database of 406 GC patients, the median overall
      survival of Nectin1 high expression patients was 55.4 months and that of low
      expression patients was 25.6 months (P = 0.0246). Using surgically or
      endoscopically resected GC samples, nectin1 expression was analyzed by
      immunohistochemistry. Nectin1 expressed at adherens junction in all the normal
      epithelial cells. However, nectin1 expressed not at adherens junction but at
      apical membrane in epithelial cells in intestinal metaplasia. The expression
      pattern of nectin1 in intestinal type GC resembled to intestinal metaplasia. In
      order to analyze the difference in nectin1 expression between GC histological
      types, a total of 116 intestinal type GC and 33 diffuse type GC. The expression
      of necitin1 in diffuse type GC (3.0%) was remarkably decreased compared to that
      in intestinal type GC (65.5%) (P < 0.0001). In conclusion, this is the first
      report showing an association between nectin1 expression and histological
      subtypes of GC.

PMID- 30221500
TI  - [Numerical Simulation on the Radiative Characteristics of the Particles in the
      Pulverized Coal Furnace].
AB  - The radiative characteristics of char and ash in the pulverized coal furnace at
      the wavelength of 560 nm are analyzed here. The particles' radiative coefficients
      are calculated in the exit of the burner and in the upper part of the furnace
      separately according to the Mie theory. It can be inferred that in the exit of
      the burner, char has a great effect on the particles' radiative coefficient,
      which accounts for a percentage of 90%. While in the upper of the furnace, ash
      dominates the particles' radiative coefficient. The scattering ratio of the ash
      is calculated to be 91.6 and the scattering ratio of the char is only 50%.

PMID- 30221499
TI  - Glaucoma Drugs in the Pipeline.
AB  - Glaucoma is a chronic disease that can be challenging to treat for both patients
      and physicians. Most patients will require more than 1 medication over time to
      maintain their intraocular pressure (IOP) at a physiologically benign level.
      Patients may become refractory to existing compounds and many struggle with
      adherence to multiple topical drop regimens. The field of glaucoma therapeutics
      has been advancing rapidly with an emphasis on compounds comprising multiple
      molecules/mechanisms of action that offer additivity and are complementary to
      current therapeutics. Several new topical drop compounds directly targeting the
      trabecular meshwork (TM)/Schlemm canal/conventional outflow pathway to reduce
      outflow resistance have obtained US Food and Drug Administration approval in the
      past year. These include rho kinase inhibitors and nitric oxide donating
      compounds. Alternative therapies that offer long-term IOP lowering while removing
      the patient from the drug delivery system are moving forward in development.
      These include gene therapy and stem cell strategies, which could ease or
      eliminate the burden of topical drop self-administration for several years.
      Additionally, a variety of novel formulations and devices are in development that
      aim for controlled, steady state delivery of therapeutics over periods of months.
      The future of glaucoma therapy is focusing on an increase in specificity for the
      individual patient: their type of glaucoma; underlying mechanisms; genetic make
      up; comorbid conditions; and rate of progression. Maintaining functional vision
      and improving patient outcomes remains the goal in glaucoma therapeutics. The
      current collection of novel therapeutics offers an expanded set of tools to
      achieve that goal.

PMID- 30221501
TI  - [Effects of Green Manures on Soil Dissolved Organic Matter in Moisture Soil in
      North China].
AB  - Soil dissolved organic matter (DOM) plays an important role in the
      biogeochemistry of carbon, nitrogen, and phosphorus and in the transport of heavy
      metals and pesticides in soil. In moisture soil, green manures and soils were
      sampled in situ at the ploughed stage of green manures. A 56-day laboratory
      incubation experiment was conducted to simulate the dynamic changes of soil DOM
      influenced by the decomposition of green manures, the green manures were Hairy
      vetch (Vicia villosa Roth.), February orchid (Orychophragmus Violaceus L.), Rye
      (Secale cereale L.), the soil without green manure was used as a control (CK).
      The composition and ultraviolet-visible spectrum parameters of soil DOM were
      investigated at different incubation stages. Results showed that green manures
      could increase the dissolved organic carbon (DOC), the total organic acids (TOAs)
      and total carbohydrate (TCs) contents, and all treatments were reached a peak on
      the 1st day and decreased later. Hairy vetch affected DOC and TOAs most and were
      increased by 114.01% and 109.10% higher than CK respectively at the 1st and 14th
      day. Rye influenced the total carbohydrate (TCs) most and was maximumly 323.18%
      higher than CK at the 42nd day. Green manures could increase the dissolved
      organic nitrogen (DON) content, DON in all green manure treatments increased on
      the 1st day, decreased several days later and increased again after 20~30 d.
      Hairy vetch effected DON best and was 305.83% higher than CK at the 42nd day. All
      green manures increased in SUVA254, SUVA260, SUVA272, SUVA280 and SAUC240-400,
      while decreasing in A250/A365 and A240/A420. The PCA analysis of ultraviolet
      visible spectrum parameters showed that SUVA254, SUVA260, SUVA272, SUVA280 had a
      high positive correlation between each other, and the same situation was found
      between A250/A365 and A240/A420. Among them, SAUC240-400 was a key factor
      parameter featuring the characteristics of DOM. The results suggested that green
      manures could increase the contents of DOM and its aromaticity, hydrophobic
      percentage, humification degree and average molecular weight, and could be
      increased and the stability of DOM could be enhanced accordingly. The ultraviolet
      visible spectrum parameters could indicate the changes of characteristics of DOM
      in this study.

PMID- 30221502
TI  - [Study on NIR Model Transfer between Similar Kinds of Fruits Based on Slope/Bias
      Algorithm].
AB  - In order to expand the application range of the model for a single kind of fruits
      in the portable near infrared instrument, this paper comes up with a new method
      for the soluble solid content (SSC) model transfer between different kinds of
      fruits. This method is focusing on the idea of model transfer between different
      instruments. Based on the similar physical and chemical properties of apples,
      peaches and pears, such as the range of SSC content, fruit size and the thickness
      of peel, a simple Slope/Bias algorithm is applied to the transfer of apple SSC
      partial least square (PLS) model. After that, it can be used to predict pear &
      peach SSC value with very little extra samples. It's more convenient and costs
      less by using this method. For pear samples, by using extra 35 standard samples
      to transfer apple SSC model, RMSEP reduced from 1.009  degrees Brix to 0.565 
      degrees Brix. For peaches, extra 40 standard samples led to a significant reduce
      of RMSEP from 1.726  degrees Brix to 0.677  degrees Brix after model transfer. To
      validate the feasibility of this model transfer method, both pear and peach SSC
      models were tested using the same Slope/Bias algorithm model transfer
      respectively. A pear SSC model was firstly set up and then transferred with
      Slope/Bias method. Taking 30 standard apples as samples, RMSEP value reached
      0.597 degrees Brix, while taking 40 standard peaches as samples, RMSEP value
      reached 0.689 degrees Brix. The peach SSC model was transferred in the same way.
      For apples, using 35 standard samples, RMSEP value reached 0.654 degrees Brix,
      and for pears, using 30 standard samples, RMSEP value reached 0.439 degrees Brix.
      These results show that slope/bias algorithm can be used to transfer model
      between similar kinds of fruits such as apples, pears and peaches. The paper
      provides innovative ideas for the model transfer among similar kinds of
      materials, so that the portable near infrared instruments can be used more
      conveniently and widely.

PMID- 30221503
TI  - [Detection System for VOCs Concentration Based on Improved Photo-Elastic
      Modulator].
AB  - Since the size of modulated crystal is limited with size in the conventional
      photo-elastic modulation system, it's a low spectrum resolution, so detection
      accuracy of gas concentration is not high. In order to improve the spectrum
      resolution of the system, an improved photo-elastic modulation system was
      designed. This method was carried out multiple reflection of incident light in
      the crystal. The optical path difference was increased by this method, so that a
      higher spectrum resolution was obtained. The entire system was constructed with
      the laser, photo-elastic modulator, polarizer, analyzer and photo-detector. Among
      them, a wedge angle (theta) was processed on modulation crystal. And a reflection
      film was plated on both sides; effective optical path length increase was
      implemented. Through the analysis the wedge angle (theta) was selected, and
      function on the optical path, the phase of modulation and the energy was
      calculated for the wedge angle. Ultimately, the appropriate wedge angle values
      were determined, and the corresponding optical path function expressions were
      given. In the experiments, the concentration of three common VOC gas was analyzed
      respectively. The concentration of sample gas was calibration by PTM400-VOC gas
      analyzer, and the results were compared with conventional photo-elastic
      modulation system. Experimental results show that gas concentration detection
      limit is reached to 0.010 mg.m-3 for improved photo-elastic modulation system,
      compared with conventional photo-elastic modulation system it's an order of
      magnitude or more. The gas concentration detection error was 3.4%, and it's also
      better than the traditional type. In summary, improved photo-elastic modulation
      system not only has the advantage of high static structural stability, but also a
      substantial increase in the spectrum resolution and detection accuracy of
      concentration.

PMID- 30221504
TI  - [Elemental Analysis of Alloys with Picosecond Dual-Pulse LA-LIBS under Low Sample
      Destruction].
AB  - A study on elemental analysis of alloy samples under low sample destruction with
      dual-pulse laser-ablation laser induced breakdown spectroscopy (LA-LIBS) based on
      one picosecond Nd : YAG laser is presented. In LA-LIBS, low pulse energy 532 nm
      laser was used for sample ablation and high  pulse energy, time-delayed 1 064 nm
      laser was used for re-excitation of the ablated samples to enhance atomic
      emissions of the laser-induced plasma and signal detection sensitivity. The
      influence of pulse energies of the ablation laser and excitation laser to the
      signal intensities was studied experimentally. I was observed that Cu 324.75 nm
      line intensity in LA-LIBS was enhanced 86 times in comparison with that obtained
      in SP-LIBS under 10 MUJ pulse energy of the ablation laser and 2.5 mJ pulse
      energy of the excitation laser. The diameter of the crater generated in LA-LIBS
      was less than 10 MUm. It is demonstrated the possibility of using dual-pulse LA
      LIBS to realize elemental analysis of solid sample under low sample destruction.
      This technique is valuable for elemental analysis of precious samples and 2D
      elements mapping under high spatial resolution.

PMID- 30221505
TI  - [Rapid Soil Classification with Laser Induced Breakdown Spectroscopy].
AB  - Soil classification is an important research content in soil science field. It is
      the basis of soil survey and resource evaluation which is important to
      agricultural production. There are many soil classification standards all over
      the world. China has two kinds of classifications including soil genetic
      classification and soil system classification. There are great differences
      between different types of soil elements, so it is feasible for soil
      classification to use laser induced breakdown spectroscopy. Laser induced
      breakdown spectroscopy (LIBS) is a new element analysis technology which uses a
      laser pulse with high energy density to ablate samples. LIBS has been used in
      many fields including environmental protection and industrial production control.
      It can directly reflect the difference of element content in different soils. The
      experimental setup including an Nd: YAG laser, a spectrometer, a computer and a
      rotating platform. In the experiment 7 kinds of soil (red soil, brick red soil,
      lateritic red soil, paddy soil, cinnamon, alluvial soil and alpine meadow soil)
      including 25 samples were used. All soil samples were grinded and sieved before
      the experiment. Under the same experimental condition, the temperatures of the
      plasma created by the laser pulses on the surface of the different soil samples
      have great differences. The lateritic red soil had the highest temperature, and
      the alpine meadow soil had the lowest. But it was not enough to form the basis
      for classification. Therefore six constant elements including Si, Fe, Al, Mg, Ca
      and Ti were selected and their spectral line intensity were treated as
      classification index. Principal component analysis (PCA) was used to simplify the
      classification process. The PCA method could simplify the 6 indexes to few
      independent indexes which could also reflect the spectral information of the 6
      elements. The original spectral data was processed by Matlab. The process
      consisted of spectral background removal, characteristic spectrum identify and
      extraction. The classification results showed a three--dimensional figure. Except
      alpine meadow soil which varied in element concentrations 6 kinds of soils
      achieved good classification. The brick red soil and lateritic red soil varied in
      PC1, but their PC2s and PC3s were the same. The two kinds of soil overlapped with
      each other and they couldn't be separated. Back-propagation artificial network
      was also used to achieve soil classification. The classification results were the
      same with the PCA. Some brick red soil and lateritic red soil samples were
      identified inaccurately. When the PC1, 2, 3 were used as the input of the BP
      neural network, the classification had much better accuracy because less input
      improved the performance of the BP-neural network. Only one alpine meadow soil
      sample was identified to cinnamon soil. When the plasma temperature was also
      taken into account, all the soil samples could be distinguished. The results
      showed that LIBS could be used to classify soils based on their element content
      differences. The PCA, soil plasma temperature and BP-neural network were useful
      tools to achieve soil classification. The LIBS provides a useful tool for general
      detailed soil survey and rational utilization of soil.

PMID- 30221506
TI  - NaYF4:Yb,Er Upconversion Nanotransducer with in Situ Fabrication of Ag2S for Near
      Infrared Light Responsive Photoelectrochemical Biosensor.
AB  - An innovative near-infrared (NIR) light-driven photoelectrochemical (PEC)
      aptasensor was constructed for sensitive screening of carcinoembryonic antigen
      (CEA) on the basis of in situ formation of Ag2S nanoparticles on the NaYF4:Yb,Er
      upconversion nanoparticles (UCNs), coupled with hybridization chain reaction
      (HCR) for the signal amplification. Utilization of UCN as the light
      nanotransducer could convert the NIR light into an applicable wavelength
      harvested by semiconductors. The multiemissions of NaYF4:Yb,Er UCN could match
      well with the absorption characteristics of Ag2S. In the presence of target CEA,
      a sandwich-type reaction was carried out between capture CEA aptamer/NaYF4:Yb,Er
      modified electrode and trigger CEA aptamer, which underwent an unbiased strand
      displacement reaction to open C-rich hairpin probes in sequence between two
      alternating hairpins with the assistance of C-Ag+-C chelation reaction. Upon
      addition of sulfide, the chelated Ag+ ions in the long-nicked DNA poly strands by
      hybridization chain reaction reacted with sulfide to generate Ag2S nanoparticles.
      The formed Ag2S could utilize effectively the upconversion emissions to amplify
      the photocurrent. Under optimal conditions, NaYF4:Yb,Er-based NIR light
      responsive PEC aptasensing platform exhibited high sensitivity for the
      determination of CEA within a dynamic linear range of 0.005-5.0 ng mL-1. The
      limit of detection was 1.9 pg mL-1. Good precision and high specificity could be
      acquired in this system for the analysis of target CEA. Human serum samples
      containing target CEA were measured using our strategy and received well-matched
      results relative to human CEA enzyme-linked immunosorbent assay kits.
      Importantly, the NaYF4:Yb,Er-based NIR light-responsive PEC aptasensing system
      provides a new ideal for the detection of disease-related biomarkers using a
      nucleic acid-based amplification strategy.

PMID- 30221507
TI  - Shape Memory Ankle-Foot Orthoses.
AB  - Electrically actuated ankle-foot orthoses (AFOs) were designed and prototyped
      using shape memory textile composites. Acrylic copolymers were synthesized as the
      matrix to demonstrate shape memory effects, whereas electrothermal fabrics were
      embedded to generate uniform heat as a trigger. Superior to conventional
      polymeric orthoses, shape memory AFOs (SM-AFOs) could be repeatedly programmed at
      least 20 times with stable shape fixity and recovery. Evidenced by clinical
      practice, SM-AFOs were effectively actuated at 10 V, allowing the correction of
      ankle angles with 10 degrees  plantarflexion. Ultimately, we envision a smart
      orthopedic system that can advance progressive rehabilitation with manipulation
      under safe and convenient conditions.

PMID- 30221508
TI  - ROMP for Metal-Organic Frameworks: An Efficient Technique toward Robust and High
      Separation Performance Membranes.
AB  - Mixed-matrix membranes (MMMs) with excellent mechanical and separation
      performance are usually challenging to be fabricated due to the significant
      incompatibility between nanofillers and the polymer matrix. This work provides a
      facile technique to construct MMMs through covalently attaching metal-organic
      frameworks (MOFs) within the polymer matrix via ring-opening metathesis
      polymerization. Norbornene-modified UiO-66-NH2 was successfully copolymerized
      into polynorbornene matrix in less than 10 min. Owing to strong covalent
      interaction among MOFs and polymers, exceptional toughening effects for MMMs
      through cavitation were observed. For MMMs with 20 wt % MOF loading, 520 times
      improvement in mechanical toughness was realized in comparison with neat polymers
      (52 vs 0.1 MJ/m3), far exceeding most of the previous MMMs. Such MMMs exhibited
      excellent gas separation performance for H2/CO2 and H2/N2 with high H2
      permeability at 91-230 barrers and H2/N2 and H2/CO2 selectivity at >1000 and 6-7,
      respectively, surpassing the 2008 Robeson Upper Bound. As a proof for the
      scalable preparation of MMMs, a large and thin MMM (dimension: 98 * 165 cm;
      thickness: 3-5 MUm) was also prepared in the factory for gas separation.

PMID- 30221509
TI  - Label-Free Monitoring of Microorganisms and Their Responses to Antibiotics Based
      on Self-Powered Microbead Sensors.
AB  - Rapid detection of bacteria and their susceptibility to specific antibiotics
      plays a vital role in microbial infection treatments. Antimicrobial
      susceptibility testing (AST) is a common measure to select effective drugs.
      However, the conventional practices, such as broth dilution, E-test, and disk
      diffusion, in clinical applications require a long turnaround time (~3 days),
      thereby compromising treatments and increasing mortality. This study presents
      self-powered sensors for on-site microorganism monitoring and rapid AST based on
      functionalized microbeads. The microbead sensors are driven by Brownian motion,
      rendering external power unnecessary. Fluorescent microbeads ( dp = 2 MUm) were
      coated with vancomycin to capture bacteria. The growth and responses of Gram
      negative Escherichia coli and Gram-positive Staphylococcus aureus under
      antibiotic treatment were evaluated. The method showed stable selective binding
      despite the presence of some interferential substances, such as proteins and
      cells. Diffusivity change was strongly related to bacterial concentration.
      Accordingly, the diffusivity values of microbeads bound with motile and nonmotile
      bacteria exhibited specific patterns because of extra motility from microbes and
      increased particle diameter. Only a drop of microbead-bacteria suspension (~5
      MUL) was needed in a microchip for each measurement. The microchip provided a
      steady environment for measurement over a few hours. By distinguishing the slope
      of the last four data points in the temporal diffusivity curve, bacterial
      susceptibility or resistance to specific antibiotics could be determined within a
      time frame of 2 h. The study provides insights into saving more lives by using a
      fast and robust AST technique in future clinical practice.

PMID- 30221510
TI  - Ozonation of Tamoxifen and Toremifene: Reaction Kinetics and Transformation
      Products.
AB  - The oxidation of the two antiestrogenic pharmaceuticals tamoxifen and toremifene
      with ozone in water was investigated concerning kinetics, reaction pathway, and
      transformation product formation. For both compounds a high dependency of second
      order rate constants and products on pH was determined. In case of full
      protonation of the amine (cation) ozone attacks with a second order rate constant
      of 1.57 * 104 M-1 s-1 for tamoxifen and 4.37 * 103 M-1 s-1 for toremifene. The
      neutral tertiary amine has an unexpected high second order rate constant of 3.17
      * 108 M-1 s-1 for tamoxifen and 1.46 * 108 M-1 s-1 for toremifene. For the
      reaction of ozone and the tertiary amine only N-oxide formation was observed. p
      Ka values for tamoxifen (9.49 +/- 0.22) and toremifene (9.57 +/- 0.22) can be
      reported based on experimental data. Eight transformation products (TPs) were
      observed and identified based on MS/MS spectra or a reference standard. Products
      observed derived from Criegee reaction and hydroxylation as well as N-oxide
      formation. Further TPs from reactions with TAM products were combinations of N
      oxides, Criegee products and hydroxylation products. Thus, reaction pathways can
      be derived and primary and secondary TPs distinguished for the first time.

PMID- 30221511
TI  - Detection of Pesticides in Aqueous Medium and in Fruit Extracts Using a Three
      Dimensional Metal-Organic Framework: Experimental and Computational Study.
AB  - A new, three-dimensional cadmium based metal-organic framework
      [Cd3(PDA)1(tz)3Cl(H2O)4].3H2O {PDA = 1,4-phenylenediacetate and tz = 1,2,4
      triazolate}, 1, has been successfully synthesized using slow diffusion method at
      room temperature. The structure of compound 1 has been determined using single
      crystal X-ray diffraction. The triazolate ligands connect three different types
      of octahedral Cd2+ ions to form a two-dimensional structure. The chloride ion and
      PDA ligands connect the two-dimensional layers to form a three-dimensional
      structure. The phase purity of 1 was confirmed by powder X-ray diffraction,
      thermogravimetric analysis, and IR spectroscopy. Aqueous dispersion of compound 1
      gives intense luminescence emission at 290 nm upon excitation at 225 nm. This
      emission was used for the luminescence based detection of pesticides, especially
      azinphos-methyl, chlorpyrifos, and parathion in aqueous medium. The selectivity
      of pesticide detection remains unaltered even in the presence of surfactant
      molecules. The mechanisms of luminescence quenching were successfully explained
      by the combination of absorption of excitation light, resonance energy transfer,
      and the possibility of electron transfer. Experimental findings are also well
      supported by the density functional theory calculations. Selectivity of
      pesticides detection in real samples such as apple and tomato juice has also been
      observed.

PMID- 30221512
TI  - Field-Induced Redistribution of Surfactants at the Oil/Water Interface Reduces
      Membrane Fouling on Electrically Conducting Carbon Nanotube UF Membranes.
AB  - Membrane-based treatment of oily wastewater remains a significant challenge,
      particularly under high salinity conditions. The main difficulty associated with
      this separation process is membrane fouling, mostly caused by wetting and
      coalescence of emulsified oil droplets on the membrane surface. In this study,
      electrically conducting carbon nanotube-based ultrafiltration membranes were used
      to treat an emulsified oil suspension at ionic strengths as high as 100 mM. By
      tuning the electrical potential applied to the membrane surface, we demonstrate
      how fouling can be dramatically reduced, even under high salinity conditions.
      Permeate water quality is shown to improve upon application of a negative
      potential. Using optical microscopy, we observed dramatic changes in the shape of
      oil droplets at the membrane/water interface in response to the applied electric
      potential; this change is associated with a redistribution of charged surfactant
      molecules at the oil/water interface in response to the external electric field.
      Specifically, using the membrane as a cathode repels surfactant molecules away
      from the oil/membrane interface, while anodic conditions lead to increased
      surfactant concentrations. We speculate that this change in surfactant molecule
      distribution is responsible for changes in the surface tension of oil droplets at
      the membrane/water interface, which results in a decrease in oil coalescence and
      subsequent fouling. The membranes used in this study offer an attractive
      treatment option when separating emulsified oil from water under high salinity
      conditions.

PMID- 30221513
TI  - A pH-Resolved Colorimetric Biosensor for Simultaneous Multiple Target Detection.
AB  - Colorimetric detection has been widely applied in daily life. However, on the
      other hand, the further development of colorimetric biosensors has been
      constrained by the lack of multiple detection capabilities. In this work, we
      proposed a pH-resolved colorimetric biosensor for the first time for the
      simultaneous detection of four targets, including ochratoxin A (OTA), aflatoxins
      B1 (AFB1), fumonisin B1 (FB1), and microcystin-LR (MC-LR). With allochroic dyes
      as the signal indicators, pH value was introduced as the new dimension to control
      the release of dyes. The concentrations of four targets can be obtained in order
      by adjusting the pH of the solution. Meanwhile, tedious and high-cost chemical
      modification processes in the fabrications of biosensors were also avoided by the
      combination of DNA-directed self-assembly of graphene oxide and magnetic
      separation. This biosensor provided a simple, rapid, accurate, and low-cost
      strategy for multiple target detection.

PMID- 30221514
TI  - Aqueous Synthesis of Copper(II)-Imidazolate Nanoparticles.
AB  - A green, simple, and efficient room-temperature aqueous synthetic route for the
      fabrication of novel porous coordination polymer nanoparticles (NPs) composed of
      Cu2+ and imidazolate was developed. Colloidal stability, morphology changes, and
      structural and chemical integrity of the developed NPs, in several solvents
      having different polarity, were investigated. Basic physicochemical properties of
      selected NPs (i.e., NP1, NP2, and NP3), such as size, optical and magnetic
      activity, porosity, thermal stability, structure, aging, and catalytic activity,
      were determined. Data indicate that the addition of the surfactant
      hexadecyltrimethylammonium bromide (CTAB) and the final solvent determine the
      size, morphology, and structure of the different NPs.

PMID- 30221515
TI  - Ion at Air-Water Interface Enhances Capillary Wave Fluctuations: Energetics of
      Ion Adsorption.
AB  - Recent simulations provide the energetics of ion adsorption at the air-water
      (a/w) interface: The presence of the ion at the interface suppresses the
      fluctuations of the capillary waves (CWs) reducing the entropy and displaces the
      weakly interacting water molecules to the bulk causing a reduction in the
      enthalpy. Here, we provide atomistic simulation-based evidence that the
      inferences of the existing studies stem from considering a small simulation
      volume that pins the CWs. For an appropriate size of the simulation system, an
      ion at the a/w interface enhances the CW fluctuations. Furthermore, we discover
      that the characteristics of the waves governing these enhanced CW fluctuations
      ensure a significant decrease in the pressure-volume work causing the enthalpy
      decrease, while the same wave characteristics of the CWs become responsible for
      an entropy decrease. Overall, the paper revisits the free energy picture of this
      fundamental problem of ion adsorption at the a/w interface.

PMID- 30221516
TI  - Cause for the Orbital Ordering of Cs2AgF4 and Its Effect on Thermoelectric
      Properties.
AB  - The cause for the orbital-ordered structure of orthorhombic Cs2AgF4 and its
      effect on thermoelectric properties were probed by density functional theory
      calculations. The orbital-ordered structure of orthorhombic Cs2AgF4 has been
      regarded as caused by a cooperative Jahn-Teller (JT) distortion of the AgF6
      octahedra of tetragonal Cs2AgF4. However, each AgF6 octahedron of tetragonal
      Cs2AgF4 is axially compressed and hence has no JT instability. The orbital
      ordering transition of Cs2AgF4 is best described as a metal-to-insulator
      transition driven by a bandgap opening at the Fermi level. The orbital-ordering
      opens a bandgap at the Fermi level and generates peaks in the density of states
      at the conduction band minimum (CBM) and valence band maximum (VBM).
      Consequently, orthorhombic Cs2AgF4 has strongly enhanced Seebeck coefficients as
      compared to tetragonal Cs2AgF4.

PMID- 30221517
TI  - Three-Dimensional Sandwich Nanocubes Composed of 13-Atom Palladium Core and
      Hexakis-Carbocycle Shell.
AB  - Coordination of cyclic unsaturated hydrocarbons to transition metal generally
      gives bis-ligated sandwich complexes, which are a fundamental class of
      organometallic compounds. This sandwich structure may be extended to a higher
      order three-dimensional one when more than two carbocyclic ligands surround an
      agglomerate of many transition metal atoms. Here, we report synthesis of three
      dimensional sandwich nanocube compounds containing a close-packed transition
      metal cluster core. Reduction of a [Pd3(MU3-C7H7)2]2+ with tetraarylborate under
      neat conditions afforded [Pd13(MU4-C7H7)6]2+ containing a cuboctahedral Pd13 core
      with an octahedral ligand-shell.

PMID- 30221518
TI  - Solar Evaporator with Controlled Salt Precipitation for Zero Liquid Discharge
      Desalination.
AB  - A sustainable supply of clean water is essential for the development of modern
      society, which has become increasingly dependent on desalination technology since
      96.5% of the water on Earth is salt water. Thousands of desalination plants are
      producing massive waste brine as byproduct, and the direct discharge of brine
      raises serious concerns about its ecological impact. The concept of zero liquid
      discharge (ZLD) desalination is regarded as the solution, but the current ZLD
      technologies are hampered by their intensive use of energy and high cost. In this
      work, a 3D cup shaped solar evaporator was fabricated to achieve ZLD desalination
      with high energy efficiency via solar distillation. It produces solid salt as the
      only byproduct and uses sunlight as the only energy source. By rationally
      separating the light absorbing surface from the salt precipitation surface, the
      light absorption of the 3D solar evaporator is no longer affected by the salt
      crust layer as in conventional 2D solar evaporators. Therefore, it can be
      operated at an extremely high salt concentration of 25 wt % without noticeable
      water evaporation rate decay in at least 120 h. This new solar evaporator design
      concept offers a promising technology especially for high salinity brine
      treatment in desalination plants to achieve greener ZLD desalination as well as
      for hypersaline industrial wastewater treatment.

PMID- 30221519
TI  - Identification of 2-Hydroxymethyl-3,6-diethyl-5-methylpyrazine as a Key
      Retronasal Burnt Flavor Compound in Soy Sauce Aroma Type Baijiu Using Sensory
      Guided Isolation Assisted by Multivariate Data Analysis.
AB  - The burnt flavor (overcooked rice flavor) is often retronasally perceived during
      the soy sauce aroma type Chinese Baijiu (Chinese distilled spirit) tasting and
      regarded as an important quality marker of the Baijiu. The sensory-guided
      isolation approach assisted by multivariate data analysis was applied to identify
      the compounds responsible for the retronasal burnt flavor in the Baijiu. Using
      two-dimensional offline high performance liquid chromatography separation and
      taste dilution analysis, a subfraction with the highest burnt flavor intensity
      was isolated from the Baijiu sample. In the subfraction, six potential flavor
      compounds were detected by ultra performance liquid chromatography-mass
      spectrometry. The most probable burnt flavor compound was screened by projection
      to latent structure regression analysis of the correlation between the potential
      compounds and their impact on burnt flavor. The target compound was identified as
      2-hydroxymethyl-3,6-diethyl-5-methylpyrazine by means of high-resolution mass
      spectrometry and chemical synthesis. Sensory evaluation revealed a relatively low
      burnt flavor threshold of 2.89 MUmol/L in 53% ethanol aqueous solution. On the
      basis of the dose-overthreshold factor and addition experiment, this compound was
      confirmed as the key contributor to the burnt flavor of soy sauce aroma type
      Baijiu.

PMID- 30221521
TI  - Stereocontrolled Synthesis of trans/ cis-2,3-Disubstituted Cyclopropane-1,1
      diesters and Applications in the Syntheses of Furanolignans.
AB  - A new Michael addition/intramolecular alkylation sequence of ( Z)-3-(2-bromo-3
      arylacryloyl)oxazolidin-2-ones and malonates was developed. By a simple switch of
      the reaction conditions including the base promoter, solvent, and reaction
      temperature, both of the cis- and trans-isomers of a series of oxazolidinone
      containing 2,3-disubstituted cyclopropane-1,1-diesters could be obtained in good
      to-excellent yields and with an excellent diastereoselectivity. The utility of
      the cyclopropane products was demonstrated in the diastereoselective syntheses of
      (+/-)-urinaligran and a stereoisomer of (+/-)-virgatusin involving the AlCl3
      promoted [3+2] annulation with veraldehyde or piperonal as the key step.

PMID- 30221520
TI  - Polymorphism in Benzene-1,3,5-tricarboxamide Supramolecular Assemblies in Water:
      A Subtle Trade-off between Structure and Dynamics.
AB  - In biology, polymorphism is a well-known phenomenon by which a discrete
      biomacromolecule can adopt multiple specific conformations in response to its
      environment. The controlled incorporation of polymorphism into noncovalent
      aqueous assemblies of synthetic small molecules is an important step toward the
      development of bioinspired responsive materials. Herein, we report on a family of
      carboxylic acid functionalized water-soluble benzene-1,3,5-tricarboxamides (BTAs)
      that self-assemble in water to form one-dimensional fibers, membranes, and hollow
      nanotubes. Interestingly, one of the BTAs with the optimized position of the
      carboxylic group in the hydrophobic domain yields nanotubes that undergo
      reversible temperature-dependent dynamic reorganizations. SAXS and Cryo-TEM data
      show the formation of elongated, well-ordered nanotubes at elevated temperatures.
      At these temperatures, increased dynamics, as measured by hydrogen-deuterium
      exchange, provide enough flexibility to the system to form well-defined nanotube
      structures with apparently defect-free tube walls. Without this flexibility, the
      assemblies are frozen into a variety of structures that are very similar at the
      supramolecular level, but less defined at the mesoscopic level.

PMID- 30221522
TI  - Enantioselective Silver-Catalyzed Cascade Synthesis of Fused Lactone and Lactam
      Oxazolines.
AB  - A new and highly stereoselective cascade reaction between isocyanoacetate esters
      and alpha-hydroxy and alpha-amino ketones has been developed. A cinchona alkaloid
      derived aminophosphine/silver(I) catalyst complex promoted the reaction and
      enabled the ready synthesis of fused bicyclic gamma-lactone and gamma-lactam
      oxazolines with high enantiocontrol (up to 99% ee).

PMID- 30221523
TI  - Synthesis and Discovery of Estra-1,3,5(10),6,8-pentaene-2,16alpha-diol.
AB  - A metallacycle-centered approach to the assembly of partially aromatic synthetic
      steroids was investigated as a means to prepare a boutique collection of unique
      steroidal agents. The synthesis and discovery of estra-1,3,5(10),6,8-pentaene
      2,16alpha-diol (VII) is described, along with structure-activity relationships
      related to its cytotoxic properties. Overall, VII was found to have a GI50 = 0.2
      MUg/mL (~800 nM) in MDA-MB-231 human breast cancer cells, be an efficacious
      estrogen receptor agonist with potency for ERbeta > ERalpha (ERbeta EC50 = 21
      nM), possess selective affinity to the cdc-2-like kinase CLK4 (Kd = 350 nM), and
      be phenotypically related to paclitaxel by an unbiased panel assessment.

PMID- 30221524
TI  - Chiral Aniline Synthesis via Stereospecific C(sp3)-C(sp2) Coupling of Boronic
      Esters with Aryl Hydrazines.
AB  - An enantiospecific coupling between alkylboronic esters and lithiated aryl
      hydrazines is described. The reaction proceeds under transition-metal-free
      conditions and is promoted by acylation of a hydrazinyl arylboronate complex,
      which triggers a N-N bond cleavage with concomitant 1,2-metalate rearrangement.
      Judicious choice of the acylating agent enabled the synthesis of ortho- and para
      substituted anilines with essentially complete enantiospecificity from a wide
      range of boronic ester substrates.

PMID- 30221525
TI  - Design and Synthesis of 2-Acetamido-2,3-dideoxythiodisaccharides via
      Diastereoselective Conjugate Addition to Sugar Enone O-Acetyl Oximes.
      Galactosidase Inhibition Studies.
AB  - The key step in a new synthesis of 2-acetamido-2,3-dideoxy-(1->4)
      thiodisaccharides was the conjugate addition of a 1-thiogalactose derivative to E
      and Z acetyl oximes derived from sugar enones. This reaction was shown to be
      completely diastereoselective for both the formation of the thioglycosidic
      linkage and the configuration of acetyl oxime. The thiodisaccharides have been
      designed as inhibitors of the beta-galactosidase from E. coli, and they have been
      shown to successfully meet such requirements.

PMID- 30221527
TI  - Screening of Hearing in Newborn Infants: Follow-Up and Outcome After 40930 Births
      in Babol, Northern Iran.
AB  - BACKGROUND: The purpose of this study was to investigate the results of hearing
      screening in all newborn infants, and their follow-up in Babol, northern Iran.
      METHODS: Between 2006 and 2014, all healthy neonates delivered in 3 hospitals
      were included in this cross-sectional study. Newborns were screened using the
      transient evoked otoacoustic emissions test before discharge. Those who failed to
      pass the examination were tested for auditory brainstem response (ABR) by the age
      of one month. The infants referred from the previous level underwent tests of
      auditory steady state response, ABR and impedance audiometry before the age of 3
      months. For infants with the diagnosis of bilateral hearing impairment, it was
      recommended to use a hearing aid in 3 months. Then, their parents were
      recommended to take infants again to the hearing testing centers within next 6
      months. If the infant's hearing was not improved, he/she was advised to undergo
      cochlear implantation. RESULTS: In total, 40930 newborns were screened. Out of
      them, 62 (1.5 per 1000 live births) were finally diagnosed to have hearing
      impairment, of whom 14 had unilateral and 48 had bilateral disorders (candidate
      for supportive measures). Overall, 986 (2.4%) were lost to follow-up and 11
      (0.03%) died over the first 3 months of age. At the end of the 6-month follow-up
      for supportive stage, 15 out of 48 infants received a hearing aid and 18 (0.4 per
      1000 children) underwent cochlear implant surgery. Fourteen out of 48 cases were
      lost to follow-up over supportive stage. CONCLUSION: It is recommended that all
      newborns undergo hearing screening test before hospital discharge, and those with
      impairment receive supportive measures from 3 months of age, and be re-examined
      at 12 months of age.

PMID- 30221526
TI  - Development and Utilization of a Palladium-Catalyzed Dehydration of Primary
      Amides To Form Nitriles.
AB  - A palladium(II) catalyst, in the presence of Selectfluor, enables the efficient
      and chemoselective transformation of primary amides into nitriles. The amides can
      be attached to aromatic rings, heteroaromatic rings, or aliphatic side chains,
      and the reactions tolerate steric bulk and electronic modification. Dehydration
      of a peptaibol containing three glutamine groups afforded structure-activity
      relationships for each glutamine residue. Thus, this dehydration can act
      similarly to an alanine scan for glutamines via synthetic mutation.

PMID- 30221528
TI  - Hypericin Induces Apoptosis in MDA-MB-175-VII Cells in Lower Dose Compared to MDA
      MB-231.
AB  - BACKGROUND: Breast cancer is the major cause of death from cancer among women
      around the world. Given the drug resistance in the treatment of this disease, it
      is very important to identify new therapies and anticancer drugs. Many studies
      demonstrated that hypericin could induce apoptosis in different cancer cell
      lines; however, the underlying mechanism is not well understood yet. Therefore,
      this study aimed to evaluate the anticancer effect of hypericin in two breast
      cancer cell lines, one with wild type P53 and the other with mutant P53. METHODS:
      In this study, the MDA-MB-231 and MDA-MB-175-VII cell lines were treated with
      different concentrations of hypericin for 24 and 48 hours. The measurement of
      cell death was performed by MTT assay. The cell apoptosis rate was measured using
      annexin V/propidium iodide assay through flow cytometry. The level of expression
      in P21 and P53 genes was evaluated by real time PCR. Immunocytochemistry (ICC)
      analysis was performed for P21 (direct target for P53 protein) to confirm the
      results. RESULTS: The results showed that hypericin could have dose-dependent
      cytotoxic effects on the MDA-MB-231 and MDA-MB-175-VII cell lines, and its
      cytotoxicity is much higher in the latter cells. According to flow cytometry
      results, 86% of MDA-MB-175-VII cells underwent apoptosis with IC50 dose of
      hypericin for MDA-MB-231 cells after 24 hours. Moreover, after 24 hours of
      exposure to hypericin with MDA- MB-231 IC50 concentration, the expression of P53
      and P21 genes upregulated in MDA-MB-175-VII much more than MDA-MB-231 when both
      cell lines were treated with 24 hours IC50 dose of MDA-MB-231. The ICC analysis
      on P21 confirmed that by treating both cell lines with MDA-MB-231 IC50 dose of
      hypericin for 24 hours, this protein is overexpressed much more in MDA-MB-175-VII
      cells. CONCLUSION: The results of this study demonstrated that hypericin's
      apoptotic and cytotoxic effects on cancer cells may be mediated via P53
      overexpression, cell cycle arrest and the subsequent apoptosis. Therefore, it is
      of great importance to consider that hypericin would have better impact on cells
      or tumors with wild type P53.

PMID- 30221529
TI  - Comparing Serum Level of Vitamin D3 in Patients With Isolated Coronary Artery
      Ectasia and Normal Coronary Artery Individuals.
AB  - BACKGROUND: Coronary artery ectasia (CAE) is identified as dilation of one or
      more segments of coronary arteries that reaches 1.5 times or more, compared with
      near segments that are normal. Several etiologies like atherosclerosis,
      autoimmune diseases and congenital anomalies have been proposed for this
      condition. Vitamin D deficiency activates the renin-angiotensin-aldosterone
      system, which affects the cardiovascular system. For these reasons, we
      investigated the serum level of vitamin D in patients with CAE compared with
      individuals with normal coronary arteries. METHODS: The study group included 30
      patients (20 males and 10 females, mean age: 57 +/- 9 years) with isolated CAE
      without any stenotic lesions, and the control group consisted of 60 age/gender
      matched subjects who had normal coronary angiograms (CAG) (40 males and 20
      females, mean age: 57 +/- 8 years). All participants underwent CAG at Tehran
      Heart Center between December 2015 and March 2016. Along with routine lab tests,
      vitamin D, serum albumin, calcium, phosphorus and alkaline phosphatase levels
      were analyzed and the unadjusted and adjusted effects of vitamin D on CAE were
      evaluated using logistic regression model. RESULTS: The median vitamin D level of
      the patients with CAE was lower than that of the control group (6.5 [3.0, 18.8]
      ng/mL vs. 17.7 [8.9, 27.1] ng/mL; P = 0.002). The logistic regression model
      showed that vitamin D deficiency was a predictor for the presence of CEA (P =
      0.013). After adjustment for confounding variables, this association remained
      significant (P = 0.025). CONCLUSION: An association between CAE and vitamin D
      deficiency was found in our study.

PMID- 30221530
TI  - Tryptophan Degradation and Antioxidant Status in Patients With Thyroid Disorders.
AB  - BACKGROUND: The aim of this study was to evaluate the degradation of tryptophan
      (Trp), neopterin production and antioxidant capacity in patients with benign and
      malignant thyroid disease. METHODS: For this reason, the levels of tryptophan,
      kynurenine (Kyn) and neopterin, and superoxide dismutase (SOD) and catalase (CAT)
      enzyme activities in 67 thyroid patients were evaluated in our study and the
      results were compared with 30 healthy controls. RESULTS: Tryptophan and
      kynurenine levels in thyroid patients decreased compared to the control group.
      Patients with thyroid disease had lower CAT activity than the control group. The
      neopterin and tryptophan levels in malignant and benign patients were also
      significantly different. CONCLUSION: The results of the present study suggest
      that thyroid disorders may lead to changes in tryptophan degradation, neopterin
      production and CAT enzyme activities.

PMID- 30221531
TI  - Epidemiology of Head and Neck Cancers in Northern Iran: A 10-Year Trend Study
      From Golestan Province.
AB  - BACKGROUND: Golestan province, in Northern Iran, is a high-risk area for
      esophageal squamous cell carcinoma (SCC). SCC is also the most common
      histological type of cancers of the head and neck region including cancers of
      oral cavity, oropharynx, hypopharynx and larynx. We aimed to present the
      incidence rate of head and neck SCC (HNSCC) in Golestan province during 2004 and
      2013. METHODS: Data on HNSCC were obtained from Golestan population-based cancer
      registry (GPCR). Quality control and data analysis were performed using CanReg
      software. Age standardized incidence rates (ASRs) were calculated using the world
      standard population. The ASRs were presented per 100000 person-years for
      different genders, residence places and years. RESULTS: During the 10-year period
      from 2004-2013, 434 cases of HNSCC were registered. 327 (75.3%) of these cases
      were male, 51.2% (222 cases) lived in urban areas and 351 (80.9%) of the total
      HNSCCs occurred in the larynx. Overall, the ASR of HNSCCs in Golestan province
      was 4.8. The ASR of HNSCCs was more than two-fold higher in male (6.6) than
      female (3.0). Our results showed an increasing trend in ASR of larynx cancer
      during the study period both in male and female. CONCLUSION: We found relatively
      high rates of larynx cancer in Golestan province. Our results also showed higher
      rates of HNSCC in males and urban population. Considering common risk factors
      between HNSCCs and esophageal cancer, further studies are needed to clarify
      different aspects of HNSCCs (including epidemiology and risk factors) in this
      high-risk population.

PMID- 30221532
TI  - Retrospective Analysis of 345 Multiple Myeloma Cases: An Investigation from 2
      Institutions.
AB  - BACKGROUND: Multiple myeloma (MM) accounts for a substantial mortality rate among
      hematological cancers. The prognosis of the disease has been noticeably changed
      during the past 2 decades. This study reports a retrospective analysis of 345 MM
      cases from 2 cancer centers. METHODS: Medical records of 345 MM cases were
      analyzed in retrospect. Diagnosis of MM was defined in presence of at least 10%
      plasma cells in bone marrow biopsy and one of the CRAB findings (hypercalcemia,
      renal failure, anemia and myeloma bone lesions). Survival analysis was performed
      using Kaplan-Meier method, and the effects of prognostic variables were assessed
      by Cox proportional hazards model. RESULTS: The mean age of the patients was
      61.98 +/- 11.44 years. Comparing to Mayo Clinic series, our patients were
      relatively younger and suffered from more advanced disease. By a median follow up
      time of 45 months, 1- and 5-year overall survival (OS) rates were 78.0% and
      35.6%, respectively. Regarding first progression free survival (PFS1), similar
      rates of 57.7% and 17.0% were observed respectively. In multivariate analysis,
      hypercalcemia (corrected serum calcium >11 mg/dL), pancytopenia and elevated
      serum creatinine (Cr) (>2 mg/dL) were found to be independent prognostic factors
      affecting OS. CONCLUSION: Presentation of MM in Iran which is a developing
      country, was significantly different from developed countries. This finding might
      be generalized to other developing countries as well. In addition, vincristine
      adriamycin-dexamethasone (VAD) therapy was an inferior protocol compared to
      bortezomib as first and second lines. Furthermore, pancytopenia was observed in
      about 9% of the patients and was an independent prognosticator of the disease.

PMID- 30221533
TI  - The Gap of Cigarette and Hookah Smoking Between Socioeconomic Groups in Iran:
      Effect of Inequalities on Socioeconomic Position.
AB  - BACKGROUND: Hookah and cigarette smoking have adverse effects on individuals'
      health and therefore place a great burden on public health. The aim of this study
      was to measure inequalities in socioeconomic position to determine contributing
      factors on cigarette and hookah smoking in Iran. METHODS: In this study,
      secondary analysis of the Iran's sixth national Surveillance of Risk Factors of
      Non-Communicable Diseases (SuRFNCD-2011) was conducted for 10,572 individuals
      aged 15 to 70 years old. Subjects were categorized into three groups according to
      their socioeconomic status (low, middle and high) in order to assess their
      inequalities using principal component analysis. At the end, the gap between the
      low and high socioeconomic groups was decomposed using Blinder-Oaxaca
      decomposition technique. RESULTS: The prevalence of cigarette and hookah smoking
      in high, middle, and low socioeconomic groups was 11.8%, 13.2%, and 13.1%
      (P=0.158), and 2.6%, 3.3% and 4.3%, (P<0.001), respectively. Blinder-Oaxaca
      decomposition technique showed a lower prevalence of hookah smoking in high
      socioeconomic group compared to low socioeconomic group (P<0.001). The gap
      between the two mentioned groups was measured to be 1.7%. However, this gap for
      cigarette smoking (1.5%) was not significant (P=0.093). CONCLUSION: The finding
      indicates the importance of socioeconomic status in hookah smoking. After
      decomposition of the gap between the 2 socioeconomic groups, age, gender and
      education level were reported to be the major contributors to the differences
      observed between the 2 groups.

PMID- 30221534
TI  - Point of Care Policy for Eliminating Hepatitis C, its Applicability and
      Acceptability.
AB  - Chronic infection with hepatitis C virus (HCV), can now be safely treated with
      oral, well-tolerated medications with >90% success rates, however, currently <5%
      of the infected individuals have been diagnosed and <1% have received treatment.
      This is believed to be due to the complicated, time-consuming and expensive
      disease management processes that require several referrals to specialized
      laboratories and hospital-based clinics, and also the epidemic of HCV infection
      among populations who have low uptake for evaluation, appointments, and
      treatment. Point of care (POC) policy emphasizes on delivering healthcare tests
      and services to patients at or near the place and time of patient care. A
      reasonable design for POC policy should contain all parts of the HCV management
      continuum including screening, diagnosis of viremia, genotyping, cirrhosis
      evaluation and treatment. Furthermore, successful implementation of this policy
      requires acceptability from the perspectives of healthcare providers, target
      populations, and policymakers. In this letter, we discuss the current
      applicability, acceptability, and cost-effectiveness of POC policy for the
      management of HCV infection.

PMID- 30221535
TI  - In Memory of Dr. Mahmoud Bahmanyar, an International Researcher of the Pasteur
      Institute of Iran.
AB  - In Iran and also throughout the world, Dr. Mahmoud Bahmanyar (1919-2007) is
      acknowledged as a well-known researcher mainly in the field of rabies and plague.
      As an expert of plague for the World Health Organization (WHO), he accomplished
      many missions in several countries such as India, Cambodia, Myanmar, Indonesia,
      Vietnam, Yemen, and Brazil. His research on rabies has played an important role
      leading to the successful combined use of immune-serum and anti-rabies vaccine
      for prevention of human rabies worldwide. He also conducted many studies in the
      field of typhus, relapsing fever, and polio. The present article aimed to review
      his activities.

PMID- 30221536
TI  - Encyclopedia of Pharmacy and Pharmaceutical Supplies in Isfahan, Iran.

PMID- 30221538
TI  - Spike-in genomic DNA for validating performance of metagenomics workflows.
AB  - Shotgun metagenomics is a powerful platform to characterize human microbiomes.
      However, to translate such survey data into consumer-relevant products or
      services, it is critical to have a robust metagenomics workflow. We present a
      tool - spike-in DNA - to assess performance of metagenomics workflows. The spike
      in is DNA from two organisms - Alivibrio fischeri and Rhodopseudomonas palustris,
      in a ratio of 4:1 added to samples before DNA extraction. With a valid workflow,
      the output ratio of relative abundances of these organisms should be close to 4.
      This expectation was tested in samples of varying diversities (n = 110), and the
      mean ratio was 4.73 (99% CI [4.0, 5.24]). We anticipate this tool to be a
      relevant community resource for assessing the quality of shotgun metagenomics
      workflows and thereby enable robust characterization of microbiomes.

PMID- 30221537
TI  - Heat stress as a predisposing factor for necrotic enteritis in broiler chicks.
AB  - Heat stress is a physical environmental stressor, which can affect performance,
      health and welfare of poultry. The present study investigates the effect of
      cyclic acute heat stress as a predisposing factor for necrotic enteritis in
      broiler chicks in an experimental challenge model. Two hundred and forty broiler
      chicks were randomly allocated to four treatment groups, as follows: group A
      served as negative control (25 degrees C), group B birds were subjected to cyclic
      acute heat stress (35 degrees C), group C birds were challenged and group D birds
      were both subjected to heat stress and challenged. From each bird, the intestine,
      gizzard and liver were collected and scored for gross lesions. The intestinal
      digesta was collected for pH and viscosity determination. One caecum from each
      bird was taken for microbiological analysis. The statistical analysis and
      evaluation of data revealed that the heat stress in challenged birds showed a
      relative trend to increase the severity and the incidence of necrotic enteritis
      lesions, although it was not considered as statistically significant (Rho =
      0.077). Additionally, the heat stress induced necrotic enteritis outbreak in
      unchallenged birds; the challenge of birds as well as its combination with the
      heat stress affected significantly (Rho <= 0.05) the pH and viscosity of
      intestinal digesta and the caecal Clostridium perfringens counts. The study
      provides evidence that cyclic acute heat stress is an environmental stressor,
      which can significantly affect necrotic enteritis and gut health, and thus should
      be taken into account in warmer areas of the world where poultry farming becomes
      a major industry.

PMID- 30221539
TI  - The association of celebrity worship with problematic Internet use, maladaptive
      daydreaming, and desire for fame.
AB  - BACKGROUND AND AIMS: Celebrity worship, defined as an obsessive fascination with
      a famous person, has been associated with several mental health problems, such as
      symptoms of depression and anxiety, dissociation, and body image concerns. The
      aim of this study was to extend the scope of investigation of previous research
      on psychological correlates by exploring the association of celebrity worship
      with compulsive behaviors, such as problematic Internet use, maladaptive
      daydreaming, desire for fame, and self-efficacy. METHODS: A voluntary sample of
      437 Hungarian adolescents and adults (78.3% male; Mage = 24.7 years, SD = 7.4)
      completed an online questionnaire focusing on attitudes toward celebrities and
      other relevant variables. RESULTS: As a result of hierarchical regression
      analyses, high levels of celebrity worship were associated with problematic
      Internet use, maladaptive daydreaming, and desire for fame. Furthermore, females
      were at higher risk to become obsessed with celebrities than males. DISCUSSION
      AND CONCLUSION: These findings provide with a more comprehensive picture of
      psychological difficulties associated with celebrity worship and may contribute
      to a better understanding of this phenomenon.

PMID- 30221540
TI  - Holmium Laser Enucleation of the Prostate: A Rebel with a Cause.

PMID- 30221541
TI  - Assessment of bleeding in chronic liver disease and coagulopathy using the
      IMPROVE bleeding criteria.
AB  - BACKGROUND: In this study, the authors utilized the IMPROVE (International
      Medical Prevention Registry on Venous Thromboembolism) bleeding definition to
      explore the safety profile of pharmacologic venous thromboembolism (VTE)
      prophylaxis in patients with chronic liver disease (CLD) and concurrent
      coagulopathy (INR >=1.5). METHODS: A retrospective study was conducted on 193
      adult patient admissions with a diagnosis of CLD and INR >=1.5 not due to
      therapeutic anticoagulation. Patients were stratified based on their receipt of
      pharmacological thromboprophylaxis or not during hospitalization. The rates of
      overall bleeding, defined as the composite of major bleeding and clinically
      relevant non-major bleeding; major bleeding; and clinically relevant non-major
      bleeding, within 14 days of admission were evaluated. Secondary endpoints
      included the rates of thrombosis and mortality. RESULTS: The composite of overall
      bleeding occurred in 17.6% of the admissions. More patients in the group not
      receiving pharmacological thromboprophylaxis had overall bleeding (18.5% vs 10%),
      major bleeding (13.3% vs 10%), and clinically relevant non-major bleeding (14.5%
      vs 5%), with overlapping 95% CI. When stratified per pharmacological
      thromboprophylaxis status, IMPROVE bleeding risk score (BRS) >= 7 was associated
      with higher rates of overall bleeding, major bleeding, and clinically relevant
      non-major bleeding as compared to IMPROVE BRS <7, whether patients received or
      did not receive pharmacological thromboprophylaxis. The overall incidence of in
      hospital mortality among our study population was 15.5%. Receiving
      pharmacological thromboprophylaxis was markedly associated with higher in
      hospital mortality (OR = 16.58, 95% CI = 4.47-61.45). CONCLUSION: This study
      shows that the IMPROVE BRS calculated on admission may serve as a guide for
      omission of thromboprophylaxis in advanced CLD.

PMID- 30221542
TI  - Measurement of Posterior Acoustic Stone Shadow on Ultrasound Is a Learnable Skill
      for Inexperienced Users to Improve Accuracy of Stone Sizing.
AB  - INTRODUCTION: Studies suggest that the width of the acoustic shadow on ultrasound
      (US) more accurately reflects true stone size than the stone width in US images.
      We evaluated the need for training in the adoption of the acoustic shadow sizing
      technique by clinical providers. METHODS: Providers without shadow sizing
      experience were recruited and assigned in a stratified, alternating manner to
      receive a training tutorial ("trained") or no intervention ("control"). Each
      conducted a baseline assessment of 24 clinical US images; where present, shadow
      width was measured using custom calipers. The trained group subsequently
      completed a standardized training module on shadow sizing. All subjects repeated
      measurements after ~1 week. Group demographics were compared using Fisher's exact
      test. Measurements were compared to clinically reported stone sizes on
      corresponding CT and US using mixed-effects models. One millimeter concordance
      between shadow and CT size was compared using a generalized linear mixed-effects
      model. RESULTS: Twenty-six subjects were included. There was no significant
      difference between groups in demographics, clinical role, or US experience. Mean
      reported CT and US stone sizes were 6.8 +/- 4.0 mm and 10.3 +/- 4.1 mm,
      respectively. At baseline, there was no difference in shadow size measurements
      between groups (p = 0.18), and shadow size was no more accurate than US stone
      size (p = 0.28 trained; p = 0.81 control), compared to CT. After training,
      overestimation bias of shadow size in the trained group decreased to 1.6 +/- 0.5
      mm (p < 0.01), relative to CT. This was not significantly associated with
      clinical rank, US experience, or stone-measuring experience. One millimeter
      concordance with CT size significantly increased from 23% to 35% of stones after
      training (p = 0.01). No significant improvement occurred in the control group.
      CONCLUSION: Acoustic shadow sizing was readily adopted by inexperienced
      providers, but was not more accurate than reported US stone sizes without
      training. Education on shadow sizing may be warranted before clinical adoption.

PMID- 30221543
TI  - Assessing exterior egg quality indicators using machine vision.
AB  - 1. The objective of this study was to develop a machine vision method for
      analysing exterior parameters of chicken eggs to automate the stage of primary
      sorting. 2. The developed algorithm based on predetermined thresholds calculated
      egg quality indicators, including geometric dimensions, shape index and the
      mottling grade. The algorithm was implemented with an experimental setup that
      combined the image-based and the candling methods. A total of 400 egg samples
      were analysed. 3. Comparison of results of the algorithm with those obtained
      using the traditional manual method showed that mean value of radii values
      difference was 0.095 +/- 0.058 mm for the sharp and 0.080 +/- 0.047 mm for the
      blunt end of the egg, with standard deviations of 0.58 mm and 0.49 mm,
      respectively. 4. The correlation coefficient between the shape index values
      determined by the two methods was 0.93; the standard deviation of absolute
      differences between corresponding values was 1.05%. 5. The results of mottling
      grade estimation were compared using F-measure and confusion matrix. 6. The
      results allow the possibility to perform the assessment of egg exterior quality
      factors in an automatic mode, independent of the expertise of a grader.

PMID- 30221544
TI  - Detection of m6A-associated SNPs as potential functional variants for coronary
      artery disease.
AB  - AIM: To investigate the effects of m6A-single nucleotide polymorphisms (SNPs) on
      coronary artery disease (CAD). METHODS: We examined the association of m6A-SNPs
      with CAD in about 185,000 cases and controls and further performed eQTL and
      differential expression analyses to support the identified m6A-SNPs. RESULTS:
      Among the 4390 m6A-SNPs detected, 304 seemed to be associated with CAD (p <
      0.05). SNP rs12286 was significantly associated with CAD at genome-wide level (p
      = 4.5 * 10-9). rs12286 was predicted to influence m6A methylation and have the
      potential to alter regulatory motifs binding, which may in turn regulate the
      expression of ADAMTS7 (p = 1.26 * 10-8). CONCLUSION: The present study found
      plenty of CAD-associated m6A-SNPs and demonstrated the potential functionality of
      the identified SNPs.

PMID- 30221545
TI  - How promising is neuroactive steroid drug discovery?

PMID- 30221546
TI  - An indole diterpenoid isolated from the fungus Drechmeria sp. and its
      antimicrobial activity.
AB  - One new indole diterpenoid, drechmerin I (1), was isolated from the fermentation
      broth of Drechmeria sp. isolated from the root of Panax notoginseng. Its
      structure was elucidated based on 1 D and 2 D nuclear magnetic resonance (NMR),
      high resolution electrospray ionization mass spectrum (HRESIMS), and electronic
      circular dichroism (ECD) spectroscopic analyses as well as TD DFT calculations of
      ECD spectra. Drechmerin I (1) was assayed for its antimicrobial activity against
      Candida albicans, Staphylococcus aureus, Bacillus cereus, B. subtillis,
      Pseudomonas aeruginosa, and Klebsiella pneumonia, respectively. Drechmerin I (1)
      showed antimicrobial activities against B. subtillis with an MIC value of 200
      MUg/mL. The interaction of S. aureus peptide deformylase with drechmerin I (1)
      was investigated by molecular docking.

PMID- 30221547
TI  - Resting Brain Functional Networks and Trait Coping.
AB  - This study aims to investigate the effects of individual differences in trait
      coping on brain networks at rest using electroencephalography (EEG) data. EEG
      recordings were processed using graph theory analysis. Active and passive coping
      styles were determined according to the factor structure of the Brief Coping
      Orientation to Problems Experienced questionnaire. A structural equation modeling
      analysis indicated that the influence of coping strategies on quality of life
      varies in strength and direction. In particular, active coping strategies were
      positively correlated with the psychological dimension. Graph measures, at both
      global and nodal levels, were used to identify the brain network properties in
      accordance with passive versus active coping styles. Preliminary evidence showed
      that both the global and nodal graph metrics were affected by the coping strategy
      in the delta band. During resting state, passive coping strategy participants had
      network topology characterized by a high global efficiency, indicating an
      important level of integration between distant brain areas and a high local
      efficiency and transitivity, suggesting a high local communication between
      adjacent regions. Various regions, such as the paracentral lobule, posterior
      cingulate, and other frontal or parietal areas, seemed to play a key role,
      suggesting that processes such as emotional load are highly solicited in passive
      coping individuals. In active coping participants, the superior temporal gyrus
      seemed to be of importance when neurons oscillated in the theta and alpha
      frequencies.

PMID- 30221548
TI  - Digital and Mechanical Characterization of Ureteral Stent Luminal Reduction in
      Response to Extrinsic Compression Forces.
AB  - PURPOSE: To investigate the principles that govern ureteral stent failure by
      digitally and mechanically characterizing their luminal reduction in response to
      various extrinsic compression forces. To explore the relationship between
      ureteral stent "material area," "luminal area," and "cross-sectional area (CSA)"
      for resisting extrinsic compression forces. MATERIALS AND METHODS: We
      mechanically investigated 4.8F (n = 9), 6F (n = 9), and 7F (n = 9) ureteral
      stents to determine parameters that contribute to resisting radial compression
      forces. Digitalized images of luminal reduction values under incrementally
      increased reductions of stent outer diameters were obtained (0%, 25%, 50%, and
      60% of original outer diameter). Forces (Newton [N]) and percentage luminal
      reduction that resulted in complete ureteral stent obstruction were determined.
      RESULTS: Uniaxial incremental compression in the radial direction demonstrated
      complete luminal reduction (95%-100%) when 58% to 62% of the outer stent diameter
      was compressed. The 6F ureteral stents demonstrated the greatest resistance to
      extrinsic compression and the greatest "material area" relative to "CSA" (mm2).
      The force (N) required for 50% compression of outer stent diameter was 10.44,
      28.13, and 25.39 N for 4.8F, 6F, and 7F ureteral stents, respectively. The
      "material area"/"CSA" at 50% compression of the outer stent diameter was 76%,
      86%, and 78% for 4.8F, 6F, and 7F ureteral stents, respectively. CONCLUSIONS:
      Maintenance of intraluminal stent diameter in the presence of extrinsic
      compressive forces is primarily dependent on the stent's ratio of "material area"
      to "CSA." Urologists should be aware of these findings to decrease the risk of
      ureteral stent failure when treating extrinsic ureteral obstruction.

PMID- 30221549
TI  - siRNAs targeting multidrug transporter genes sensitize breast tumor to
      doxorubicin in a syngeneic mouse model.
AB  - Chemotherapy, the commonly favored approach to treat cancer is frequently
      associated with treatment failure and recurrence of disease as a result of
      development of multidrug resistance (MDR) with concomitant over-expression of
      drug efflux proteins on cancer cells. One of the most widely used drugs,
      doxorubicin (Dox) is a substrate of three different ATP-binding cassette (ABC)
      transporters, namely, ABCB1, ABCG2 and ABCC1, predominantly contributing to MDR
      phenotype in cancer. To silence these transporter-coding genes and thus enhance
      the therapeutic efficacy of Dox, pH-sensitive carbonate apatite (CA)
      nanoparticles (NPs) were employed as a carrier system to co-deliver siRNAs
      against these genes and Dox in breast cancer cells and in a syngeneic breast
      cancer mouse model. siRNAs and Dox were complexed with NPs by incubation at 37
      degrees C and used to treat cancer cell lines to check cell viability and caspase
      mediated signal. 4T1 cells induced breast cancer mouse model was used for
      treatment with the complex to confirm their action in tumour regression. Smaller
      (~ 200 nm) and less polydisperse NPs that were taken up more effectively by tumor
      tissue could enhance Dox chemosensitivity, significantly reducing the tumor size
      in a very low dose of Dox (0.34 mg/Kg), in contrast to the limited effect
      observed in breast cancer cell lines. The study thus proposes that simultaneous
      delivery of siRNAs against transporter genes and doxorubicin with the help of CA
      NPs could be a potential therapeutic intervention in effectively treating MDR
      breast cancer.

PMID- 30221550
TI  - Towards a better understanding of postprandial hyperglycemic episodes in people
      with diabetes: impact on daily functioning.
AB  - OBJECTIVE: Acute postprandial hyperglycemia (aPPHG) is often symptomatic and can
      be associated with behavioral changes such as impaired working memory and
      attention. However, there is little evidence of the impact of aPPHG on the daily
      lives of patients. The aim of this study was to explore the frequency and
      severity of aPPHG episodes and their impact on daily functioning in people with
      insulin-treated diabetes. METHODS: Adults (n = 1200) with insulin-treated
      diabetes mellitus type 1 (T1DM) or 2 (T2DM), most of whom experienced aPPHG, were
      recruited to complete an online cross-sectional survey in the USA and UK. The
      survey captured self-reported severity and frequency of aPPHG episodes and
      included a newly developed questionnaire (aPPHG-Q) assessing the impact of aPPHG
      episodes on patients' daily lives. Data was analyzed separately according to
      diabetes type and country. Regression analyses were used to assess the
      relationship between severity or frequency and scores on the aPPHG-Q. RESULTS:
      Between 70% and 86% of USA, and 87% and 88% of UK participants reported
      experiencing aPPHG episodes. Increasing frequency and severity of aPPHG episodes
      were associated with worse scores on the aPPHG-Q in patients with both T1DM and
      T2DM in both countries (p < .014) on all subscale scores (excluding the worry and
      concerns scores for T1DM in the UK), although the magnitude of the association
      was smaller for aPPHG frequency. CONCLUSIONS: Increased severity and frequency of
      aPPHG episodes in patients with insulin-treated diabetes is associated with
      greater burden and experience of symptoms, and can negatively impact daily
      functioning.

PMID- 30221551
TI  - Consumption of beta-glucans to spice up T cell treatment of tumors: a review.
AB  - INTRODUCTION: Adoptive T-cell treatments of solid cancers have evolved into a
      robust therapy with objective response rates surpassing those of standardized
      treatments. Unfortunately, only a limited fraction of patients shows durable
      responses, which is considered to be due to a T cell-suppressive tumor
      microenvironment (TME). Here we argue that naturally occurring beta-glucans can
      enable reversion of such T cell suppression by engaging innate immune cells and
      enhancing numbers and function of lymphocyte effectors. Areas covered: This
      review summarizes timely reports with respect to absorption, trafficking and
      immune stimulatory effects of beta-glucans, particularly in relation to innate
      immune cells. Furthermore, we list effects toward well-being and immune functions
      in healthy subjects as well as cancer patients treated with orally administered
      beta-glucans, extended with effects of beta-glucan treatments in mouse cancer
      models. Expert opinion: Beta-glucans, when present in food and following uptake
      in the proximal gut, stimulate immune cells present in gut-associated lymphoid
      tissue and initiate highly conserved pro-inflammatory pathways. When tested in
      mouse cancer models, beta-glucans result in better control of tumor growth and
      shift the TME toward a T cell-sensitive environment. Along these lines, we
      advocate that intake of beta-glucans provides an accessible and immune
      potentiating adjuvant when combined with adoptive T-cell treatments of cancer.

PMID- 30221552
TI  - Steroids interfere with human carbonic anhydrase activity by using alternative
      binding mechanisms.
AB  - Bile acids have been shown to inhibit human (h) carbonic anhydrases (CA, EC
      4.2.1.1) along the gastrointestinal tract, including hCA II. The elucidation of
      the hormonal inhibition mechanism of the bile acid cholate to hCA II was provided
      in 2014 by X-ray crystallography. Herein, we extend the inhibition study to a
      wealth of steroids against four relevant hCA isoforms. Steroids displaying
      pendants and functional groups of the carboxylate, phenolic or sulfonate types
      appended at the tetracyclic ring were shown to inhibit the cytosolic CA II and
      the tumor-associated, transmembrane CA IX in a medium micromolar range (38.9-89.9
      uM). Docking studies displayed the different chemotypes CA inhibition mechanisms.
      Molecular dynamics (MD) gave insights on the stability over time of hyocholic
      acid binding to CA II.

PMID- 30221553
TI  - Safety and efficacy of propofol anesthesia for pediatric target-controlled
      infusion in children below 3 years of age: a retrospective observational study.
AB  - BACKGROUND: Although the requirement of propofol in children is increasing,
      propofol for induction and maintenance of anesthesia below 3 years old has not
      been approved in Korea. This study can provide a clinical evidence to increase
      the range of approval. RESEARCH DESIGN AND METHODS: We reviewed the medical
      records of patients below 3 years of age who underwent surgery between September
      2013 and December 2016. Safety was evaluated on the basis of vital signs, and
      laboratory findings and efficacy were evaluated on the basis of the bispectral
      index (BIS). Adverse events were examined. RESULTS: A total of 109 patients
      anesthetized with propofol (propofol group) were compared with 109 patients with
      volatile anesthetics (volatile group) after propensity score matching. There was
      a difference in the proportion of patients showing decreased systolic pressure (P
      < 0.001) and heart rate (P = 0.03), but there was no difference in diastolic
      pressure (P = 0.238), mean arterial pressure (P = 0.175) during surgery. After
      surgery, there was no difference in all vital signs and the proportion patients
      who experienced adverse events of two groups. CONCLUSIONS: Propofol anesthesia by
      target-controlled infusion was effective and didn't show serious propofol-related
      perioperative adverse events.

PMID- 30221555
TI  - Alterations of drug-metabolizing enzymes and transporters under diabetic
      conditions: what is the potential clinical significance?
AB  - There will be 642 million people worldwide by 2040 suffering from diabetes
      mellitus. Long-term multidrug therapy aims to achieve normal glycemia and
      minimize complications, and avoid severe hypoglycemic events. The appreciation of
      the drug-metabolizing enzymes and drug transporters as critical players in the
      treatment of diabetes has attracted much attention regarding their potential
      alterations in the pathogenesis of the disease. This review discusses
      pharmacokinetics-based alterations of cytochrome P450 enzymes, phase-II
      metabolizing enzymes, and membrane transporter proteins, as well as the potential
      mechanisms underlying these alterations. We also discuss the potential influences
      of altered enzymes and transporters on the disposition of commonly prescribed
      glucose-lowering medicines. Future studies should delve into the impact of
      altered drug-metabolizing enzymes and transporters on the progression toward
      abnormal glucose homeostasis.

PMID- 30221554
TI  - Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by
      combining scaffold hopping and ligand-based drug design.
AB  - Several bacteria rely on the reductive sulphur assimilation pathway, absent in
      mammals, to synthesise cysteine. Reduction of virulence and decrease in
      antibiotic resistance have already been associated with mutations on the genes
      that codify cysteine biosynthetic enzymes. Therefore, inhibition of cysteine
      biosynthesis has emerged as a promising strategy to find new potential agents for
      the treatment of bacterial infection. Following our previous efforts to explore
      OASS inhibition and to expand and diversify our library, a scaffold hopping
      approach was carried out, with the aim of identifying a novel fragment for
      further development. This novel chemical tool, endowed with favourable
      pharmacological characteristics, was successfully developed, and a preliminary
      Structure-Activity Relationship investigation was carried out.

PMID- 30221557
TI  - Optimal duration of dual antiplatelet therapy after PCI: integrating procedural
      complexity, bleeding risk and the acuteness of clinical presentation.
AB  - INTRODUCTION: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor
      inhibitor constitutes the standard of care to prevent major adverse cardiac
      events in patients who undergo percutaneous coronary intervention (PCI) with drug
      eluting stents (DES). However, the anti-ischemic benefits of DAPT are
      counterbalanced by an increased risk of hemorrhagic complications, which are
      known to be associated with increased morbidity and mortality. While the efficacy
      of DAPT in patients presenting with acute coronary syndrome (ACS) has been well
      established, the risk-benefit balance of DAPT in other subsets of patients remain
      controversial. As a result, multiple risk scores to inform optimal duration of
      DAPT have been developed recently for individuals with various degrees of
      coronary artery disease. Areas covered: Authors summarize the current evidence
      and guideline recommendations on the optimal duration and intensity of DAPT
      across the spectrum of coronary artery disease including those who undergo
      complex PCI and recapitulated the recently developed risk scores to inform
      clinical decision on the optimal duration of DAPT. Expert commentary: Clinical
      decision-making for upfront duration of DAPT after PCI with DES should consider
      the individual bleeding risk profile, the initial clinical presentation and the
      complexity of coronary stenting.

PMID- 30221556
TI  - Golimumab in the treatment of psoriatic arthritis.
AB  - INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory arthritis that can be
      aggressive and destructive, resulting in significant morbidity. While many new
      agents have been approved for the treatment of PsA over the past decade, TNF
      inhibitors (TNFi)remain an anchor treatment, in part based on extensive clinical
      experience. Recently, the TNFi golimumab was approved for intravenous use in PsA.
      Areas covered: This expert review presents an overview of the currently available
      treatment options for PsA with a focus on the evidence from clinical trials
      supporting the use of golimumab in PsA. This information is placed in context
      with recent advances in the understanding of PsA pathogenesis and treatment.
      Expert commentary: The rapid growth of treatment options available for PsA has
      brought the prospect of personalized treatment selection closer to reality but
      improved understanding of the domains of PsA and new biomarkers may be needed
      before such changes reach the clinic. Until patients who are most likely to
      benefit from a given agent can be identified and then treated accordingly, TNFi
      will likely remain a central option and their further development, such as the
      introduction of an intravenous form of golimumab, remains an important part of
      treatment improvement.

PMID- 30221558
TI  - Deep brain stimulation for childhood dystonia: current evidence and emerging
      practice.
AB  - INTRODUCTION: Dystonia, one of the most common childhood movement disorders, is
      often medically refractory and can lead to profound impacts on the child and
      their caretakers' quality of life. Limited efficacy of pharmacological treatments
      has fueled enthusiasm for innovative neurosurgical approaches, notably deep brain
      stimulation (DBS) as a treatment for refractory dystonia. Areas covered: DBS is
      increasingly applied to successfully treat childhood dystonia. While generally
      safe and effective, results vary widely depending on underlying dystonia
      etiology. The current work synthesizes and highlights advances in research
      pertaining to the use of DBS for childhood dystonia. The efficacy of DBS for
      children and youth with dystonia is discussed, with analysis divided among
      etiological subtypes. The role of DBS as a lifesaving treatment for status
      dystonicus is also reviewed. Expert commentary: When carefully selected, certain
      children and youth with dystonia experience significant symptomatic improvement
      after DBS. Beyond dystonic symptoms, DBS can improve quality of life and reduce
      caretaker burden.

PMID- 30221559
TI  - Effective early detection of oral cancer using a simple and inexpensive point of
      care device in oral rinses.
AB  - INTRODUCTION: Head and neck cancer remains a challenging disease that is
      increasing in incidence with the majority of patients diagnosed at an advanced
      stage where 5-year survival is approximately 50%. Current approaches including
      oral-brush biopsies, fluorescence-based technologies,  and salivary molecular
      profiling have demonstrated some success; however, cost, ease of use, and
      accuracy remain limiting factors. Areas covered: This is a profile of a novel,
      easy to use oral rinse point-of-care (POC) test to aid in the diagnosis of oral
      and oropharyngeal cancer. Background science related to the challenge of oral and
      oropharyngeal cancer and natural history of diagnostic aids for this disease are
      provided. Results of studies performed for validation of a POC and laboratory
      test are also discussed. Expert commentary: The POC test has been validated
      through a case : control clinical study and a prospective European trial, using
      version 1.0 (v1.0), which have demonstrated consistent performance including a >
      90% negative predictive value, with a sensitivity of 80%. The assay was designed
      to identify malignant lesions in the oral cavity and oropharynx by improving upon
      standard clinical assessment.

PMID- 30221560
TI  - The clinical implementation of copy number detection in the age of next
      generation sequencing.
AB  - INTRODUCTION: The role of copy number variants (CNVs) in disease is now well
      established. In parallel NGS technologies, such as long-read technologies, there
      is continual development and data analysis methods continue to be refined.
      Clinical exome sequencing data is now a reality for many diagnostic laboratories
      in both congenital genetics and oncology. This provides the ability to detect and
      report both SNVs and structural variants, including CNVs, using a single assay
      for a wide range of patient cohorts. Areas covered: Currently, whole-genome
      sequencing is mainly restricted to research applications and clinical utility
      studies. Furthermore, detecting the full-size spectrum of CNVs as well as somatic
      events remains difficult for both exome and whole-genome sequencing. As a result,
      the full extent of genomic variants in an individual's genome is still largely
      unknown. Recently, new sequencing technologies have been introduced which
      maintain the long-range genomic context, aiding the detection of CNVs and
      structural variants. Expert commentary: The development of long-read sequencing
      promises to resolve many CNV and SV detection issues but is yet to become
      established. The current challenge for clinical CNV detection is how to fully
      exploit all the data which is generated by high throughput sequencing
      technologies.

PMID- 30221561
TI  - Total artificial heart implantation as a bridge to transplantation: a viable
      model for the future?
AB  - INTRODUCTION: Since the first total artificial heart (TAH) surgery in a human
      patient performed in 1969, over 1300 devices have been implanted worldwide.
      Patients are benefiting from increased lengths of durable support and indications
      have expanded beyond biventricular failure including allograft failure, severe
      restrictive disease, and complex congenital anomalies. Areas covered: The role of
      the TAH in biventricular failure, rates of successful bridge-to-transplant (BTT),
      and survival compared with biventricular assist devices (BiVADs) are discussed
      and differences between TAH and LVAD patient populations are highlighted. The
      device's niche role in physiologies not amenable to single ventricle support is
      further described. New developments such as the 50cc Syncardia, continuous flow
      mechanisms (BiVACOR and Cleveland Clinic CF-TAH), and a bioprosthetic model
      (CARMAT) are discussed. Literature review was conducted utilizing the PubMed
      database selecting published research, database analyses, and case reports under
      'total artificial heart' relevant to the paper's aims. Expert commentary: TAH
      patients have high rates of successful BTT and survival on par with BiVAD
      supported patients. Ongoing developments including decreased device size,
      continuous flow mechanisms, and use of bioprosthetic materials will ensure that
      the TAH will have an increasing role in advanced heart failure with increased
      device longevity and decreased post-implant complications.

PMID- 30221562
TI  - The role of extended infusion beta-lactams in the treatment of bloodstream
      infections in patients with liver cirrhosis.
AB  - INTRODUCTION: Bloodstream infections (BSIs) in patients with liver cirrhosis are
      associated with significant morbidity and mortality. Early appropriated
      antibiotic treatment is essential for the correct management of these patients.
      Areas covered: This review covers several aspects of how the
      pharmacokinetic/pharmacodynamic behavior of antimicrobials may change in patients
      with liver cirrhosis. Common features of cirrhosis, including hypoproteinemia,
      third space expansion and impairment of renal function may alter drug
      distribution in patients receiving hydrophilic drugs like beta-lactams, which are
      often frontline agents. beta-lactams exhibit time-dependent pharmacodynamics and
      achieve maximal bacterial killing when serum drug and tissue concentrations
      exceed a multiple of the minimal inhibitory concentration (MIC) during the dosing
      interval (%fT>MIC). Administration of beta-lactams by extended infusion
      strategies improves the rate of this pharmacodynamic target attainment and has
      been associated with improved outcomes in several randomized trials in critically
      ill patients. Expert commentary: Observational studies have suggested that
      cirrhotic patients have improved outcomes when beta-lactam therapy is
      administered by extended or continuum infusion. Given the multiple
      pathophysiological features of liver cirrhosis that impact antimicrobial behavior
      and the high incidence of multidrug resistance in this population, additional
      studies are needed to understand how cirrhosis affects the pharmacokinetics and
      pharmacodynamics of antibacterial therapy.

PMID- 30221563
TI  - Insights into endotoxin-mediated lung inflammation and future treatment
      strategies.
AB  - INTRODUCTION: Airway inflammatory disorders are prevalent diseases in need of
      better management and new therapeutics. Immunotherapies offer a solution to the
      problem of corticosteroid resistance. Areas covered: The current review focuses
      on lipopolysaccharide (Gram-negative bacterial endotoxin)-mediated inflammation
      in the lung and the animal models used to study related diseases. Endotoxin
      induced lung pathology is usually initiated by antigen presenting cells (APC). We
      will discuss different subsets of APC including lung dendritic cells and
      macrophages, and their role in responding to endotoxin and environmental
      challenges. Expert commentary: The pharmacotherapeutic considerations to combat
      airway inflammation should cost-effectively improve quality of life with
      sustainable and safe strategies. Selectively targeting APCs in the lung offer the
      potential for a promising new strategy for the better management and treatment of
      inflammatory lung disease.

PMID- 30221564
TI  - Adding two culture-specific 'bolt-on' dimensions on the Thai version of EQ-5D-5L:
      an exploratory study in patients with diabetes.
AB  - BACKGROUND: This study explored whether addition of culture-specific bolt-on
      dimensions, 'interpersonal relationships (IR)' and 'activities related to bending
      knees (AK)' improves the relevance and validity of the EQ-5D among Thai patients
      with diabetes. METHODS: A cross-sectional study was conducted among 200 diabetic
      patients. Ceiling/floor effects, known-groups validity and test-retest
      reliability were evaluated. Hierarchical multiple regressions was performed to
      evaluate the incremental value of the EQ-5D+AK+IR over the EQ-5D-5L in predicting
      utility measured by visual analog scale (VAS). RESULTS: The EQ-5D+AK+IR reduced
      ceiling effects by 34%. For known-groups validity, women and lower educated
      patients reported more AK problems (p-value< 0.05); however, none of the IR
      dimension hypotheses were supported. Both IR and AK had the weighted kappa
      coefficients of 0.49, indicating good reliability. Hierarchical multiple
      regression found that adding AK (adjusted r2: 0.182 vs 0.156), but not IR
      (adjusted r2: 0.157 vs 0.156) significantly increased the explained variance in
      VAS score. CONCLUSION: Preliminary findings suggest that AK, but not IR, may be a
      useful addition to the EQ-5D questionnaire for use with Thai patients. Further
      studies in diverse populations are needed to examine the impacts of the proposed
      new dimensions and determine if these cultural adaptations are justified.

PMID- 30221565
TI  - Contemporary techniques in percutaneous coronary intervention for bifurcation
      lesions.
AB  - INTRODUCTION: Treatment of coronary bifurcation lesions with contemporary state
      of-the-art percutaneous coronary intervention (PCI) is still associated with
      higher rate of adverse cardiovascular events compared to non-bifurcation lesions.
      Bench testing and virtual computer modeling have increased our understanding of
      bifurcation PCI guiding refinement in bifurcation techniques. New insights on
      bifurcation PCI have the potential to further improve clinical outcomes in
      patients presenting with bifurcation lesions. Areas covered: The present
      manuscript aims to review the methods for bifurcation lesion assessment and
      treatment strategy step by step supported on bench and clinical evidence. Expert
      commentary: Invasive pressure-wire evaluation is essential to determine the
      appropriateness of bifurcation PCI, particularly in intermediate coronary
      stenosis. Treatment strategy relies on four parameters: diameters of the three
      segments of the bifurcation; lesion length and plaque distribution; and
      bifurcation angle. The optimal technique for bifurcation PCI is still debated, an
      individualized approach with an initial provisional side branch stenting strategy
      seems to be suitable in the 75 to 95% of patients. For more complex bifurcations,
      two-stent techniques may be required with increasing evidence supporting the
      usefulness of the double kissing balloon crush (DK-crush) technique.

PMID- 30221566
TI  - Progesterone-loaded nanosized transethosomes for vaginal permeation enhancement:
      formulation, statistical optimization, and clinical evaluation in anovulatory
      polycystic ovary syndrome.
AB  - Bio-identical progesterone (PRG) is an exogenous female steroidal hormone which
      is used for treatment of polycystic ovary syndrome (PCOS). However, it suffers
      from poor bioavailability due to hepatic metabolism and poor solubility. The
      target of this work was to evaluate and statistically optimize PRG-loaded
      nanovesicle transethosomes (NVTEs) based in mucoadhesive gel for transvaginal
      delivery of PRG as potential luteal-phase support. A 24 full factorial design was
      used to explore the effect of phosphatidylcholine (PC), Tween 80, cetyltrimethyl
      ammonium bromide and ethanol concentration on particle size, entrapment
      efficiency (EE%), % in vitro PRG release after 24 h and transvaginal flux. PRG
      loaded NVTEs were prepared by injection sonication method. The results revealed
      that the mean particle sizes ranged from 133.3 +/- 3.42 to 349.5 +/- 1.24 nm,
      zeta potential ranged from -23.5 +/- 3.84 to +74.6 +/- 4.97 mV, EE% ranged from
      87.93 +/- 3.58 to 97.05 +/- 2.61%, % PRG release ranged from 50.9 +/- 2.75 to
      90.69 +/- 2.07 and transvaginal flux ranged from 0.274 +/- 0.03 to 0.531 +/- 0.04
      mg/cm2/h. The optimized formulation was subjected to transmission electron
      microscope for morphological examination and then incorporated in the
      mucoadhesive vaginal gel using Carbopol 974, hydroxyl propyl methylcellulose and
      sodium alginate. The optimized formulation was clinically studied in anovulatory
      PCOS and showed a significant increase in the serum PRG, endometrial thickness,
      echogenicity degree and the pregnancy rate. Briefly, PRG-loaded NVTEs vaginal gel
      might be a promising formulation for luteal phase support and increase pregnancy
      rate in anovulatory PCOS.

PMID- 30221567
TI  - Comments to Professor Halliwell's article "Artefacts with ascorbate and other
      redox-active compounds in cell culture: epigenetic modifications, and cell
      killing due to hydrogen peroxide generation in cell culture media".

PMID- 30221568
TI  - Evaluation of bilosomes as nanocarriers for transdermal delivery of tizanidine
      hydrochloride: in vitro and ex vivo optimization.
AB  - Bilosomes were developed in order to investigate their efficacy as nanocarriers
      for transdermal delivery of Tizanidine HCl (TZN), a skeletal muscle relaxant with
      low oral bioavailability. Full factorial experimental design consisting of 27
      combinations was generated to study the effects of surfactant type, surfactant-to
      cholesterol ratio and the amount of bile salt on the entrapment efficiency (EE),
      the vesicle size (VS) and in vitro dissolution of the TZN-loaded bilosomes. The
      permeation through the stratum cornea was optimized with the vertical diffusion
      assembly using excised rat skin. The permeation parameters of the selected
      bilosomes were compared to the unformulated drug and it was shown that TZN-B24
      exhibited the highest enhancement ratio (ER = 8.8).The optimal formula (TZN-B24)
      consisting of span 60 in a ratio with cholesterol of 1:1 and 20 mg of bile salt
      was obtained by employing the desirability function of Design-Expert(r) software.
      The mathematical model used for the optimization was validated by comparing the
      predicted values of the EE (82.3%) and the VS (165.8 nm) with the experimental
      values of EE = 84.42% and of VS = 161.95 nm. TZN-B24 displayed high zeta
      potential which contributed to its good stability. It was evident from the
      results of this study that incorporating TZN in bilosomes improved significantly
      its permeation through the skin barrier and thus bilosomes can offer a potential
      nanoplatform using the transdermal route to improve the bioavailability of the
      drug.

PMID- 30221569
TI  - Polymorphisms and haplotypes in VDR gene are associated with female idiopathic
      infertility.
AB  - Unexplained infertility refers to the absence of a definable cause of
      reproductive failure. Vitamin D receptor (VDR) acts as a transcription factor and
      regulates a number of vitamin D-responsive genes, including those involved in the
      immune system. Recent finding that VDR is expressed in reproductive tissues
      suggests a possible importance of vitamin D in pregnancy. We conducted a case
      control study to examine the association of polymorphisms in VDR gene with
      reproductive success. DNA from 117 female patients with unexplained infertility
      and 130 fertile controls was isolated from peripheral blood and VDR genotypes
      (FokI, BsmI, ApaI and TaqI) were detected by PCR-RFLP. Haplotypes were determined
      using Haploview software. Our results show significant association of FokI and
      BsmI polymorphisms with infertility (p < 0.05). The haplotype analysis confirmed
      strong linkage disequilibrium between closely positioned BsmI, ApaI and TaqI
      polymorphisms. Two haplotypes were associated with infertility: (i) haplotype bAT
      was increasing the risk for secondary infertility; while (ii) haplotype BAT had a
      protective role against primary infertility (p < 0.05). By changing the
      expression and the activity of VDR gene, which leads to the change in expression
      of vitamin D-responsive genes, these polymorphisms and haplotypes could possibly
      have an effect on immune system in the female reproductive tract.

PMID- 30221570
TI  - Influence of body mass index on the relationship between endometrial thickness
      and pregnancy outcome in single blastocyst frozen embryo transfer cycles.
AB  - To date there is limited published data assessing whether body mass index (BMI)
      influences endometrial thickness (ET) and whether this impacts on pregnancy
      outcomes in single blastocyst FET cycles. The objective of this study, therefore,
      was to examine the relationship between BMI and ET on the outcome of single
      blastocyst FET cycles over a five-year period from 2012 until 2016. Patient age,
      BMI, endometrial pattern and ET prior to FET were recorded. Pregnancy outcomes
      included: implantation rate, clinical pregnancy rate and live birth rate. A total
      of 464 cycles met the inclusion criteria and the female age was 36.0 +/- 3.0
      years (mean +/- SD). The mean +/- SD BMI was 23.3 +/- 3.1 kg/m2 and median +/- SD
      ET was 8.1 +/- 1.5 mm. BMI and ET were modestly correlated (Pearson r = 0.244)
      and there was an association between higher BMI category and higher median ET
      (7.2, 8.0, 8.3, 8.9 mm; p < 0.001). However, there was no association between ET
      and pregnancy outcome, either unadjusted, or adjusted for BMI, age, endometrial
      pattern or embryo quality. The data suggests that although ET increases with
      increasing BMI, there are no differences in cycle outcome. Importantly, this
      implies that an ET <8 mm may not jeopardize pregnancy outcome in women with lower
      BMI. The development of a norm referenced test for BMI and ET may prove to be a
      helpful adjunct in the clinical IVF setting.

PMID- 30221571
TI  - Real-world data on the efficacy and safety of apremilast in Japanese patients
      with plaque psoriasis.
AB  - BACKGROUND: Real-world data differ from clinical trial data. Although some real
      world data regarding apremilast use for psoriasis treatment has been reported in
      Western countries, no such data has been reported in Asian countries. OBJECTIVE:
      To study the efficacy, including Psoriasis Area and Severity Index (PASI) and
      drug survival, and safety of apremilast in Japanese patients with psoriasis.
      METHODS: Data on all the patients treated with apremilast in Kurume University
      Hospital between May 2017 and June 2018 were retrieved, with June 30 2018, as the
      data lock date. Efficacy was analyzed by PASI50, PASI75, and PASI90; drug
      survival by Kaplan-Meier analysis; and drug safety by the proportion of adverse
      events (AEs). RESULTS: Fourteen of 42 (33.3%) patients achieved PASI75/90; 16
      (32%) patients had discontinued apremilast by the data lock date. Drug survival
      at week 28 was 70%. No serious AEs were reported; the most prevalent one was
      loose stools/diarrhea (60%), followed by nausea (38%). The most common reason for
      apremilast discontinuation was primary/secondary failure. CONCLUSIONS: Apremilast
      is safe and effective in Japanese patients with psoriasis. Higher occurrence of
      loose stools/diarrhea was noted in our cohort than that reported in Western real
      world studies on apremilast.

PMID- 30221572
TI  - Bacteremia in autoimmune bullous disease patients undergoing double-filtration
      plasmapheresis.
AB  - BACKGROUND: Plasmapheresis is one of the treatment options for autoimmune bullous
      disease (AIBD). OBJECTIVE: To evaluate the incidence of adverse events occurring
      during a course of plasmapheresis. METHODS: This study enrolled 42 courses of
      double-filtration plasmapheresis (DFPP) from 28 patients with AIBD treated in
      Kurume University Hospital between 2007 and 2016. We examined the frequency of
      adverse events during the course of DFPP and associated features. RESULTS: The
      most frequent adverse event was bacteremia (13 of 42 courses, 31.0%), followed by
      subcutaneous hemorrhage (1 course, 2.4%), and an abscess at the catheterization
      sites (1 course, 2.4%). No adverse event-related death was recorded. In the
      analysis of bacteremia occurrence, the erosion at the catheterization sites, the
      use of central venous catheter (CVC), and the number of DFPP cycles per course
      were significantly more or greater in the bacteremia group than in the non
      bacteremia group (p = .0474, .0005, and .0035, respectively). CONCLUSIONS:
      Although DFPP is a good treatment option for AIBD, attention needs to be paid for
      the development of possible risks during a DFPP course. We believe that our
      results can be applied to other plasmaphereses in AIBD management.

PMID- 30221573
TI  - Real-world effectiveness and safety of adalimumab for treatment of ankylosing
      spondylitis in Japan.
AB  - OBJECTIVE: To evaluate the real-world effectiveness and safety of adalimumab for
      the treatment of ankylosing spondylitis (AS) in Japan. METHODS: All AS patients
      initiated on adalimumab from 27 October 2010 to 28 May 2015, were enrolled.
      Patient characteristics at baseline, changes in Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI) scores, and adverse drug reactions (ADRs) for 24
      weeks from the first adalimumab treatment were evaluated. RESULTS: Of 403
      enrolled patients, 396 and 374 comprised the safety and effectiveness analysis
      sets, respectively. In the safety analysis set, 266/396 (67.2%) were males, with
      a mean +/- standard deviation (SD) age of 46.3 +/- 15.6 years and mean +/- SD
      disease duration of 9.8 +/- 9.8 years. Of 236 patients examined for human
      leukocyte antigen (HLA)-B27, 131 (55.5%) were HLA-B27-positive. In the
      effectiveness analysis set, the mean +/- SD BASDAI score was 4.9 +/- 2.3 at
      baseline (n = 292). Overall, 216 patients had BASDAI data pre- and post-baseline.
      At 24 weeks, 143 patients had BASDAI scores, and the mean +/- SD decrease was 
      2.0 +/- 2.6 (p < .0001). Fifteen serious ADRs occurred in 15 (3.79%) patients; 30
      (7.58%) ADRs of infections were reported, of which, five (1.26%) were serious.
      CONCLUSION: Safety and effectiveness of adalimumab in this postmarketing
      observational study were similar to that in previous clinical trials.

PMID- 30221574
TI  - Tumor-specific CD8-positive T cell-mediated antitumor immunity is implicated in
      the antitumor effect of local hyperthermia.
AB  - PURPOSE: This study aimed to elucidate the contribution of T cell-mediated
      antitumor immunity in the antitumor effect of local hyperthermia (LH). MATERIALS
      AND METHODS: C57BL/6J mice were injected with the mouse lymphoma cell line, E.G7
      OVA, in the right femur on day 0. LH was induced by immersing the right femur in
      a water bath at 42  degrees C for 60 min on day 7, followed by administration of
      anti-CD8 monoclonal antibodies (mAb) or anti-CTLA-4 mAb (days 8, 11, and 14). The
      effect of LH on tumor growth (TG) was assessed by measuring the duration until
      tumor volume reached 1000 mm3 and survival time. Tumor-specific T cell responses
      were measured using enzyme-linked immunospot (ELISpot) assay. RESULTS: TG with
      and without LH treatment was 9.0 +/- 9.6 and 7.0 +/- 1.6 days, respectively. TG
      was significantly slower with LH treatment (p = .01). The therapeutic effect of
      LH was mitigated by addition of anti-CD8 mAb (p < .05 for both TG and survival)
      compared with the untreated (control) group. Furthermore, addition of anti-CTLA-4
      mAb did not significantly affect the therapeutic effect of LH. The ELISpot assay
      showed that the number of spots in the LH group (276.3 +/- 14.5) was
      significantly greater than in the control group (59.0 +/- 4.5, p < .001).
      CONCLUSION: CD8-positive T cell-mediated antitumor immunity significantly
      contributes to the antitumor effect of LH.

PMID- 30221575
TI  - Characterization of multi-locus imprinting disturbances and underlying genetic
      defects in patients with chromosome 11p15.5 related imprinting disorders.
AB  - The identification of multilocus imprinting disturbances (MLID) appears
      fundamental to uncover molecular pathways underlying imprinting disorders (IDs)
      and to complete clinical diagnosis of patients. However, MLID genetic associated
      mechanisms remain largely unknown. To characterize MLID in Beckwith-Wiedemann
      (BWS) and Silver-Russell (SRS) syndromes, we profiled by MassARRAY the
      methylation of 12 imprinted differentially methylated regions (iDMRs) in 21 BWS
      and 7 SRS patients with chromosome 11p15.5 epimutations. MLID was identified in
      50% of BWS and 29% of SRS patients as a maternal hypomethylation syndrome. By
      next-generation sequencing, we searched for putative MLID-causative mutations in
      genes involved in methylation establishment/maintenance and found two novel
      missense mutations possibly causative of MLID: one in NLRP2, affecting ADP
      binding and protein activity, and one in ZFP42, likely leading to loss of DNA
      binding specificity. Both variants were paternally inherited. In silico protein
      modelling allowed to define the functional effect of these mutations. We found
      that MLID is very frequent in BWS/SRS. In addition, since MLID-BWS patients in
      our cohort show a peculiar pattern of BWS-associated clinical signs, MLID test
      could be important for a comprehensive clinical assessment. Finally, we
      highlighted the possible involvement of ZFP42 variants in MLID development and
      confirmed NLRP2 as causative locus in BWS-MLID.

PMID- 30221576
TI  - Abstracts for the 2019 NAEMSP Scientific Assembly.
AB  - BACKGROUND: The approach to managing out-of-hospital cardiac arrest (OOHCA) has
      generally involved either minimal on-scene resuscitation to reduce time to
      arrival at hospital or extended care at the scene to increase the chance of
      return of spontaneous circulation (ROSC) before transport. This study compared
      patient outcomes across EMS agencies with respect to the duration of on-scene
      time. We hypothesized that EMS agencies with greater average time on-scene would
      have more favorable outcomes. METHODS: The Cardiac Arrest Registry to Enhance
      Survival (CARES) was used to identify OOHCA cases, including characteristics and
      outcomes. EMS agencies were included if they submitted at least 80 OOHCAs from
      2013 to 2017. To study outcomes based upon culture of OOHCA management, outcomes
      were studied by EMS agency rather than by individual patient cases. Agencies in
      the top and bottom quartiles of on-scene time duration were categorized as high
      (HOSTAs) and low on-scene time agencies (LOSTAs), respectively. Generalized
      estimating equation models compared HOSTAs and LOSTAs. RESULTS: We classified 89
      agencies as HOSTAs (24,114 patients, average >=25 minutes on scene) and 89
      agencies as LOSTAs (37,297 patients, average <18.9 minutes on-scene). Among
      patients transported, HOSTAs were more likely to have a shockable rhythm (28.4%
      vs. 22.2%, OR = 1.4, 95%CI 1.2 to 1.5), a witnessed arrest (65.1% vs. 53.6%, OR =
      1.7, 95% CI 1.5 to 1.9), and receive bystander CPR (41.9% vs. 37.0%, OR = 1.3,
      95% CI 1.1 to 1.5) than LOSTAs, all p < 0.001. When controlling for these and
      other patient characteristics, including mechanical CPR device use, HOSTAs had a
      higher proportion of ROSC on emergency department arrival (66.7% vs. 31.1%, OR =
      4.6, 95%CI 3.5 to 6.0, p < 0.001), survival to discharge for transported patients
      (22.3% vs. 11.2%, OR = 2.6, 95%CI 2.0 to 3.4, p < 0.001), and good neurologic
      outcome among survivors (84.9% vs. 78.6%, OR = 1.3, 95%CI = 1.0 to 1.7, p = 0.04)
      than LOSTAs. CONCLUSIONS: This study suggests that HOSTAs have more favorable
      patient outcomes compared to LOSTAs. RESULTS indicate that spending more time on
      scene performing resuscitation is associated with higher rates of ROSC, survival
      and survival with good neurologic function.

PMID- 30221578
TI  - Does cognitive flexibility training enhance subjective mental functioning in
      healthy older adults?
AB  - Declining cognitive abilities in older adults can contribute to significant
      changes in socioemotional health and substantially reduce their perception of
      well-being. Whereas much attention has been dedicated to creating cognitive
      training programs to improve cognitive health in old age, there is little
      emphasis on the consequences of such interventions for subjective mental
      functioning. We created a randomized controlled trial in which we evaluated the
      effects of an adaptive computerized cognitive flexibility training. Healthy older
      adults (60-80 years old) were assigned to one of three conditions (frequent or
      infrequent switching or active control group) and performed 58 half-hour sessions
      within a period of 12 weeks. We measured effects on subjective cognitive failures
      and executive dysfunctioning, everyday functioning, depressive symptoms, anxiety,
      and quality of life, before, and after training. Additionally, participants'
      proxies rated their cognitive failures and executive dysfunctioning. Subjective
      cognitive failures and executive dysfunctioning improved 4 weeks posttraining in
      all groups, although effect sizes were low (np2 = .058 and .079, respectively)
      and there were no differences between groups (all p's > .38). No significant
      changes in subjective reports were seen directly after training, which was the
      case in all groups. Proxies did not report any functional changes over time, yet
      their evaluations were significantly more favorable than those of the
      participants, both pretraining (p < .0005) and posttraining (p = .004). Although
      we found no evidence of improvement on subjective mental functioning, we adduce
      several factors that encourage further research into the effects of computerized
      cognitive training on subjective performance.

PMID- 30221577
TI  - Streptococcus suis synthesizes deoxyadenosine and adenosine by 5'-nucleotidase to
      dampen host immune responses.
AB  - Streptococcus suis is a major porcine bacterial pathogen and emerging zoonotic
      agent. S. suis 5'-nucleotidase is able to convert adenosine monophosphate to
      adenosine, resulting in inhibiting neutrophil functions in vitro and it is an
      important virulence factor. Here, we show that S. suis 5'-nucleotidase not only
      enables producing 2'-deoxyadenosine from 2'-deoxyadenosine monophosphate by the
      enzymatic assay and reversed-phase high performance liquid chromatography (RP
      HPLC) analysis in vitro, but also synthesizes both 2'-deoxyadenosine and
      adenosine in mouse blood in vivo by RP-HPLC and liquid chromatography with tandem
      mass spectrometry analyses. Cellular cytotoxicity assay and Western blot analysis
      indicated that the production of 2'-deoxyadenosine by 5'-nucleotidase triggered
      the death of mouse macrophages RAW 264.7 in a caspase-3-dependent way. The in
      vivo infection experiment showed that 2'-deoxyadenosine synthesized by 5'
      nucleotidase caused monocytopenia in mouse blood. The in vivo transcriptome
      analysis in mouse blood showed the inhibitory effect of 5'-nucleotidase on
      neutrophil functions and immune responses probably mediated through the
      generation of adenosine. Taken together, these findings indicate that S. suis
      synthesizes 2'-deoxyadenosine and adenosine by 5'-nucleotidase to dampen host
      immune responses, which represents a new mechanism of S. suis pathogenesis.

PMID- 30221579
TI  - Circulating Epithelial Cell Characterization and Correlation with Remission and
      Survival in Patients with Thyroid Cancer.
AB  - BACKGROUND: Thyroid cancer is the most common endocrine tumor and generally has
      relatively good clinical outcomes. However, 15-20% of patients ultimately develop
      recurrence or disease-related death. The appropriate prognostic factors for
      thyroid cancer are still elusive. This study evaluated whether the number of
      circulating tumor cells/circulating epithelial cells (CECs) expressing either
      epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN), or thyrotropin
      receptor (TSHR) is related to remission and disease-specific mortality (DSM) of
      patients with thyroid cancer. METHODS: Blood samples were collected from patients
      (n = 128) after thyroidectomy or radioactive iodide therapy. CECs were enriched
      by lysis of red blood cells and depletion of leukocytes. Subtyping and
      quantification of the enriched cells were performed with immunofluorescence
      staining using antibodies against EpCAM, TSHR, and PDPN, respectively. Whether
      the number of a specific subtype of CECs is related to remission and DSM of
      patients was determined by univariate and multivariate analyses. RESULTS: The
      EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts for patients in the non-remission
      group (n = 43) were significantly higher when compared to the remission group (n
      = 85; p < 0.001). Receiver operating characteristic analysis showed that the
      number of EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was able to distinguish the
      status of remission from non-remission. The cutoff point for EpCAM+-CECs, TSHR+
      CECs, and PDPN+-CECs was 40, 47, and 14 (cells/mL), with the accuracy of the
      assay equivalent to 80.4%, 76.6%, and 77.3%, respectively. On the other hand, the
      number of EpCAM+-CECs (p < 0.001), PDPN+-CECs (p = 0.013), and TSHR+-CECs (p <
      0.001) for patients in the DSM group (n = 17) was significantly higher when
      compared to the patients who survived (n = 111). Receiver operating
      characteristic analysis showed that EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs
      counts were able to distinguish mortality from survival status. The cutoff point
      for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 27, 25, and 9 (cells/mL), with
      the accuracy of the assay equivalent to 69.5%, 67.2%, and 68.5%, respectively.
      CONCLUSIONS: CEC testing is a useful tool for analysis of overall survival and
      remission status of patients with thyroid cancer. Implementation of CEC testing
      into routine clinical test may be worthy to consider for patient clinical care.

PMID- 30221580
TI  - Can you elaborate on that? Addressing participants' need for cognition in
      computer-tailored health behavior interventions.
AB  - Computer-tailored interventions, which deliver health messages adjusted based on
      characteristics of the message recipient, can effectively improve a range of
      health behaviours. Typically, the content of the message is tailored to user
      demographics, health behaviours and social cognitive factors (e.g., intentions,
      attitudes, self-efficacy, perceived social support) to increase message
      relevance, and thus the extent to which the message is read, considered and
      translated into attitude and behaviour change. Some researchers have suggested
      that the efficacy of computer-tailored interventions may be further enhanced by
      adapting messages to suit recipients' need for cognition (NFC) - a personality
      trait describing how individuals tend to process information. However, the likely
      impact of doing so, especially when tailored in conjunction with other variables,
      requires further consideration. It is possible that intervention effects may be
      reduced in some circumstances due to interactions with other variables (e.g.,
      perceived relevance) that also influence information processing. From a practical
      point of view, it is also necessary to consider how to optimally operationalise
      and measure NFC if it is to be a useful tailoring variable. This paper aims to
      facilitate further research in this area by critically examining these issues
      based on relevant theories and existing evidence.

PMID- 30221581
TI  - The past thirty years of emotion research: appraisal and beyond.
AB  - For this Special Issue, I highlight the past and present importance of appraisal
      theory as well as the challenges to its status as a total theory of emotions from
      the other functions of emotions: associative learning, self-regulation and social
      communication. This theoretical view applies both to emotion research in general
      and the specific fields of my interest in the emotions of moral judgment and
      intergroup processes. Methodologically, developments in analyses of large and
      more naturally occurring data sets will give an opportunity to square
      psychology's structural models of discrete emotions with the more complicated
      reality that exists. Both for the field and for individual researchers picking up
      the study of emotions, my advice is to pay special attention to measures, their
      assumptions and their context.

PMID- 30221582
TI  - Activating Adiponectin Signaling with Exogenous AdipoRon Reduces Myelin Lipid
      Accumulation and Suppresses Macrophage Recruitment after Spinal Cord Injury.
AB  - Myelin-laden macrophages (mye-MPhi), resulting primarily from internalization of
      myelin debris by infiltrating bone marrow-derived macrophages in spinal cord
      injury (SCI), trigger inflammatory responses that largely contribute to secondary
      injury. Adiponectin, which is secreted from adipose tissue, is an important
      hormone that modulates macrophage inflammation. In the present study, we examined
      the role of adiponectin on macrophage-mediated neuroinflammation after SCI. We
      found that in vitro activation of adiponectin receptors (AdipoRs) by their
      agonist AdipoRon suppressed myelin lipid accumulation in mye-MPhi through
      APPL1/PPARgamma/LXRalpha/ABCA1-mediated lipid efflux, subsequently inhibiting
      inflammation and restoring normal function to mye-MPhi. In vivo data further
      confirmed that intravenous administration of AdipoRon after SCI dampened
      recruitment of macrophages and reduced myelin lipid accumulation. Accordingly,
      AdipoRon treatment ameliorated post-SCI tissue damage and astrogliosis, resulting
      in improved motor function. Although there was no significant pathological
      exacerbation in adiponectin-null mice subjected to SCI, our work reveals a
      functional link between adiponectin and hematogenous macrophages in the context
      of SCI, suggesting that activation of adiponectin signaling is a promising
      therapeutic approach to mitigate mye-MPhi-mediated neuroinflammation in
      neurological disorders involving demyelination.

PMID- 30221583
TI  - Use of Fluorescent Microsphere-Based Assay for Detection of Three Cucurbit
      Infecting Viruses.
AB  - In this study, we describe multiplex polymerase chain reaction (PCR) coupled with
      the LiquiChip assay for the identification of Zucchini yellow mosaic virus,
      Cucumber green mottle mosaic virus, and Cucumber mosaic virus by coamplification
      with plant mRNA as an internal control. Multiplex reverse-transcription (RT)-PCR
      products were subjected to allele-specific primer extension, then hybridized to
      carboxylated microspheres with unique fluorescent identifiers followed by
      detection using the LiquiChip 200 workstation. This assay is highly specific for
      distinguishing individual viruses from a mixed viral population and is 10 times
      more sensitive than multiplex RT-PCR. In addition, the establishment of this
      method enabled the detection of cucurbit viruses in field samples.

PMID- 30221585
TI  - Kicking foot swing planes and support leg kinematics in rugby place kicking:
      Differences between accurate and inaccurate kickers.
AB  - Place kicking is a complex whole-body movement that contributes 45% of the points
      scored in international Rugby Union. This study compared the kicking foot swing
      plane characteristics of accurate and inaccurate kickers, underpinned by
      differences in their support leg and pelvis kinematics at support foot contact,
      to identify key technique characteristics. Motion capture data (240 Hz) were
      collected from 33 experienced kickers, and distinct groups of accurate (n = 18)
      and inaccurate (n = 8) kickers were identified based on their performance
      characteristics. All accurate kickers were capable of kicking successfully from
      at least 33.3 m, whereas all inaccurate kickers would have missed left from
      distances greater than 30.7 m. The accurate group exhibited a moderately
      shallower swing plane inclination (50.6 +/- 4.8 degrees  vs. 54.3 +/- 2.1 degrees
      ) and directed the plane moderately further to the right of the target (20.2 +/-
      5.4 degrees  vs. 16.7 +/- 4.1 degrees ). At support foot contact, the accurate
      group placed their support foot moderately less far behind the ball (0.08 +/-
      0.08 m vs. 0.12 +/- 0.04 m) and positioned their centre of mass moderately
      further to the support leg side (0.77 +/- 0.07 m vs. 0.72 +/- 0.01 m) due to a
      moderately greater stance leg lean (29.3 +/- 4.1 degrees  vs. 26.8 +/- 3.2
      degrees ). The kicking foot swing plane is highly planar in rugby place kicking
      but its orientation differs between accurate and inaccurate kickers. These plane
      characteristics may be controlled by support foot placement and support leg and
      pelvis kinematics at support foot contact.

PMID- 30221584
TI  - Multi-target visual search organisation across the lifespan: cancellation task
      performance in a large and demographically stratified sample of healthy adults.
AB  - Accurate tests of cognition are vital in (neuro)psychology. Cancellation tasks
      are popular tests of attention and executive function, in which participants find
      and 'cancel' targets among distractors. Despite extensive use in neurological
      patients, it remains unclear whether demographic variables (that vary among
      patients) affect cancellation performance. Here, we describe performance in 523
      healthy participants of a web-based cancellation task. Age, sex, and level of
      education did not affect cancellation performance in this sample. We provide norm
      scores for indices of spatial bias, perseverations, revisits, processing speed,
      and search organisation. Furthermore, a cluster analysis identified four
      cognitive profiles among participants, characterised by many omissions (N=18),
      many revisits (N=18), relatively poor search organisation (N=125), and relatively
      good search organisation (N=362). Thus, patient scores pertaining to search
      organisation should be interpreted cautiously: Given the large proportion of
      healthy individuals with poor search organisation, disorganised search in
      patients might be pre-existing rather than disorder-related.

PMID- 30221586
TI  - The impact of cognitive interventions on cognitive symptoms in idiopathic
      Parkinson's disease: a systematic review.
AB  - This systematic review addressed efficacy of cognitive stimulation (CS),
      cognitive training (CT), and cognitive rehabilitation (CR) to improve cognitive
      functions in Parkinson's disease (PD) with (PD-MCI) and without mild cognitive
      impairment (PD-H). Five databases were searched. Twelve CT, four CS, and a
      combination of CT with CR were found. PD-H benefited from CT or CS compared to
      active or passive controls in 42.1% of cognitive tests, and in 33.3% of
      psychological and functional measures. PD-MCI alone, compared with controls, only
      improved in 6.9% of cognitive measures after CT. PD-H and PD-MCI, alone or
      together, somehow improved information processing speed, attention, working
      memory, executive functions, and visual episodic memory. PD-MCI improved better
      than PD-H in global cognition and planning abilities. The outcomes suggest some
      efficacy of cognitive interventions in PD. However, small samples, lack of
      information regarding standardization of interventions, and poor methodological
      quality limit results validity and prevent firm conclusions.

PMID- 30221587
TI  - Fabricating Muscle-Neuron Constructs with Improved Contractile Force Generation.
AB  - Tissue-engineered skeletal muscle constructs have attracted significant attention
      in the field of regenerative medicine. However, the contractile force produced by
      tissue-engineered skeletal muscle constructs is not comparable with that of
      natural skeletal muscle tissues. To improve contractile force generation of
      tissue-engineered skeletal muscle constructs, we investigated the effects of co
      culturing C2C12 myoblasts with PC12 neural cells in the fabrication of skeletal
      muscle tissue constructs. Immunocytochemical analysis revealed differentiation of
      C2C12 myotubes and outgrowth of PC12 neurites toward the aligned myotubes with
      improved betaIII-tubulin-positive neuronal area, suggesting enhanced neural
      differentiation of PC12 cells. Furthermore, co-culturing with PC12 cells improved
      the formation of sarcomeres and contractile activities of C2C12 myotubes, while
      the addition of nerve growth factor enhanced PC12 neurite outgrowth and further
      enhanced C2C12 myotube contractile activities. Formation of neuromuscular
      junctions in the C2C12/PC12 co-culture system was evidenced by the formation of
      acetylcholine receptor clusters, chemical inhibition of contractile myotubes, and
      expression of agrin. We then applied this co-culture system to the fabrication of
      neuron-incorporated skeletal muscle constructs using the magnetic force-based
      tissue engineering technique. In response to electrical pulses, the co-cultured
      tissue constructs generated maximum twitch (65.8 MUN/mm2) and tetanic (135.1
      MUN/mm2) forces that were twofold higher than those of C2C12 monocultured
      constructs (twitch force, 36.3 MUN/mm2; tetanic force, 65.9 MUN/mm2). These
      results indicate that the nerve cell-incorporated skeletal muscle tissues
      constructed in this study could be used in drug testing and biological research
      for neuromuscular diseases.

PMID- 30221588
TI  - Assessment of the efficacy of an autogenous vaccine against Yersinia
      pseudotuberculosis in young Merino sheep.
AB  - AIMS To assess the efficacy of an autogenous vaccine against Yersinia
      pseudotuberculosis III in preventing clinical disease and deaths due to
      yersiniosis in young Merino sheep, and to determine the effect of vaccination on
      the prevalence of faecal shedding of pathogenic Yersinia spp., daily liveweight
      gain, and development of antibodies to Yersinia spp. following vaccination and
      natural exposure. METHODS In six groups (three groups each from two farms) of
      young Merino sheep, 148-150 animals were systematically allocated to be
      vaccinated twice with an autogenous, formalin- killed bacterin vaccine containing
      Y. pseudotuberculosis serotype III or to remain non-vaccinated. All vaccinated
      and non-vaccinated sheep were run together in their original groups throughout
      the trial. Faecal and blood samples were collected, and liveweight measured, at
      the time of vaccination and subsequently over a 6-month period to determine
      faecal shedding of Y. enterocolitica and Y. pseudotuberculosis, seroprevalence of
      antibodies to Yersinia outer membrane proteins (YOP) and changes in liveweight.
      RESULTS None of the six trial groups experienced an outbreak of clinical
      yersiniosis during the study period. On Farm A, the prevalence of shedding of
      either or both Yersinia spp. was <40% on all but one sampling occasions. On Farm
      B the prevalence of shedding of both Yersinia spp. peaked at 98%, 96 days after
      vaccination. Mean liveweight and daily liveweight gain at the end of the study
      were similar in vaccinated and non-vaccinated groups on both farms (p>0.1), as
      was the prevalence of faecal shedding of Yersinia spp. (p>0.2), and the
      proportion of animals that became seropositive for antibodies to YOP following
      vaccination (p>0.1). CONCLUSIONS AND CLINICAL RELEVANCE This vaccine had, at
      most, limited effects on seroconversion and, under the conditions of this study,
      had no demonstrable impact on liveweight, mean daily liveweight gain or faecal
      shedding of Yersinia spp. Further studies are needed to determine the efficacy of
      this vaccine during outbreaks of yersiniosis or following experimental challenge
      with pathogenic Yersinia spp..

PMID- 30221589
TI  - Moderators and predictors of outcomes in telephone delivered compared to face-to
      face cognitive behaviour therapy for paediatric obsessive-compulsive disorder:
      preliminary evidence from a non-inferiority RCT.
AB  - This study provides a preliminary exploration of factors which differentially
      predict treatment response to telephone-delivered cognitive behavioural therapy
      (TCBT) compared to face-to-face CBT (CBT) in a randomised non-inferiority
      controlled trial of 72 children (aged 11-18 years) with obsessive-compulsive
      disorder (OCD). Potential moderator variables, their interaction with treatment
      group (CBT, TCBT) and baseline levels of OCD severity were entered into separate
      regression models where the primary outcome measure was the post-intervention
      Children's Yale-Brown Obsessive-Compulsive Scale total score (CYBOCS). Separate
      regressions were also used to test associations between predictors and outcome
      controlling for pretreatment CYBOCS. Only pretreatment level of parent-rated
      child peer problems moderated the effects of the two interventions on CYBOCS
      severity at post-treatment. After controlling for baseline CYBOCS, only family
      accommodation rated by mothers predicted poorer outcomes in both groups. While
      CBT and TCBT may be equally effective for adolescents with OCD, the current
      results tentatively suggest that higher baseline level of peer problems
      strengthened the response to therapy for youth receiving TCBT and the predictor
      analyses reinforce the importance of directly addressing family accommodation
      during CBT for paediatric OCD regardless of delivery mode. Limitations of the
      current findings and directions for future work are discussed.

PMID- 30221590
TI  - An ergonomic evaluation of pannists.
AB  - Instrumentalists and specifically percussionists have been found to develop
      musculoskeletal disorders (MSDs) due to the nature of their work. This study
      aimed to assess the MSD risk factors associated with playing the steel pan, which
      was invented in Trinidad and Tobago in the 20th century. A sample of 13 pannists
      and 13 non-pannists completed a modified Nordic Musculoskeletal Questionnaire and
      data analysis included multiple correlations, Student's t test, the Moore-Garg
      strain index and calculation of compressive force at the L5/S1 vertebrae. The
      prevalence of pain was found to be greater among the pannists; a strain index of
      22.78 was calculated and the compressive force was determined to be 4507.8 N,
      which indicated that pannists have a high risk of developing MSDs of the upper
      limbs and lower back. The risk factors identified for the development of MSDs
      were similar to those of previous studies.

PMID- 30221591
TI  - Negative impact of severity of pain on mood, social life and general activity in
      Parkinson's disease.
AB  - OBJECTIVE: Pain is an important non-motor symptom of Parkinson's disease (PD);
      however, it remains understudied. The purpose of previous studies on the
      relationship between PD and pain, has been to explore the cause, origin and types
      of pain. This case control study is designed for clinicians and rehabilitation
      specialists to effectively identify pain from the patient's point of view. Pain
      present in PD patients correlates with significant disruption to their daily
      lives, which was seen by analysing characteristics, frequency, severity and
      interference of pain. METHOD: A total of 100 PD patients and 100 control healthy
      individuals, consisting of 66 males and 34 females were evaluated during routine
      clinical assessment followed by a neurological exam. The Brief Pain Inventory
      (BPI) was used to measure chronic pain in terms of pain severity, pain
      interference and pain frequency between the two groups. RESULTS: It was
      determined that PD patients had significantly higher pain severity scores
      compared to controls (p < 0.05). PD patients with depressive symptoms had
      significantly higher pain severity and pain interference scores than controls
      without depressive symptoms. PD patients reported greater scores on Global BPI
      pain interference and all components of the pain interference subscale.
      DISCUSSION: PD and depression seem to be correlated with higher perceived pain,
      severity and interference. These findings have not been reported by other case
      control studies, and warrant further causal research into pain, depression and
      PD.

PMID- 30221592
TI  - Interaction effects of washing and abrasion on thermal protective performance of
      flame-retardant fabrics.
AB  - In this study, common flame-retardant fabrics were treated with single washing or
      abrasion and their interactions to simulate wearing away during use. The changes
      in thickness, mass/m2 and protective performance of the fabrics under both flame
      and radiation environments were evaluated. Results demonstrated that the
      protective performance was firstly increased after washing or abrasion, and then
      decreased with further increasing washing or abrasion cycles. After certain
      treatment cycles, the combined effect of washing and abrasion was significantly
      greater than the single effect of washing or abrasion alone. The interaction
      modes of washing and abrasion also showed significant differences in protective
      performance under a flame test. Under radiation exposure, the effect of combined
      washing and abrasion was more obvious. There was a positive correlation between
      the fabric weight and its protective performance with different treatments. The
      findings provide useful guidance for the actual use and maintenance of protective
      clothing.

PMID- 30221593
TI  - Functional metagenomics: a tool to gain knowledge for agronomic and veterinary
      sciences.
AB  - The increased global demand for food production has motivated agroindustries to
      increase their own levels of production. Scientific efforts have contributed to
      improving these production systems, aiding to solve problems and establishing
      novel conceptual views and sustainable alternatives to cope with the increasing
      demand. Although microorganisms are key players in biological systems and may
      drive certain desired responses toward food production, little is known about the
      microbial communities that constitute the microbiomes associated with
      agricultural and veterinary activities. Understanding the diversity, structure
      and in situ interactions of microbes, together with how these interactions occur
      within microbial communities and with respect to their environments (including
      hosts), constitutes a major challenge with an enormous relevance for agriculture
      and biotechnology. The emergence of high-throughput sequencing technologies,
      together with novel and more accessible bioinformatics tools, has allowed
      researchers to learn more about the functional potential and functional activity
      of these microbial communities. These tools constitute a relevant approach for
      understanding the metabolic processes that can occur or are currently occurring
      in a given system and for implementing novel strategies focused on solving
      production problems or improving sustainability. Several 'omics' sciences and
      their applications in agriculture are discussed in this review, and the usage of
      functional metagenomics is proposed to achieve substantial advances for food
      agroindustries and veterinary sciences.

PMID- 30221594
TI  - Branching immune pathways in psoriasis and its significance for disease severity
      assessment.

PMID- 30221598
TI  - Formulation development of self-nanoemulsifying drug delivery system of celecoxib
      for the management of oral cavity inflammation.
AB  - The oral administration of celecoxib (CLX) is a real problem because of its low
      aqueous solubility that results in high variability in absorption and its severe
      adverse effect such as cardiotoxic effects and gastrointestinal toxicity. Self
      nanoemulsifying drug delivery systems (SNEDDS) can enhance the poor dissolution
      and erratic absorption of poorly water-soluble drugs such as CLX. This study was
      conducted to investigate the potential of SNEDDS to enhance the efficacy of CLX
      on inflamed mucous tissue and reduce systemic adverse effects by increasing its
      poor dissolution properties. A pseudo-ternary phase diagram was derived from the
      results of CLX solubility experiments in various excipients. These studies
      revealed the use of Labrafil M 2515 CS as oil, tween 80 as a surfactant, and
      polyethylene glycol 400 as a co-surfactant for the optimization of SNEDDS
      formulations. Eight formulations were formulated and characterized by their
      particle size, polydispersity index, viscosity, globular shape, drug solubility,
      self-emulsification efficiency, in vitro drug release, and permeation. The anti
      inflammatory effect of CLX-SNEDDS was evaluated by carrageenan-induced cheek
      oedema in rats. The cheeks were treated with CLX-SNEDDS before oedema induction
      and then noticed for narrow periods (2 h) followed by histopathological studies
      to determine the efficacy of treatment. The selected formulations (F3 and F5)
      showed spherical morphologies under transmission electron microscopy, mean
      droplet sizes of 116.9 +/- 1.78 and 124 +/- 1.87 nm, respectively, complete in
      vitro drug release, and high cumulative amounts of drug permeation in 8 h. They
      also showed significant remarkable cheek oedema inhibition in comparison with the
      control groups (p < 0.05). CLX-SNEDDS was found to achieve effective local
      therapeutic concentration and intended to reduce cheek oedema, congestive
      capillary, inflammatory cells, and side effects due to lower dose size.

PMID- 30221599
TI  - Drug Target Selection for Trypanosoma cruzi Metabolism by Metabolic Control
      Analysis and Kinetic Modeling.
AB  - In the search for therapeutic targets in the intermediary metabolism of
      trypanosomatids the gene essentiality criterion as determined by using knock-out
      and knock-down genetic strategies is commonly applied. As most of the evaluated
      enzymes/transporters have turned out to be essential for parasite survival,
      additional criteria and approaches are clearly required for suitable drug target
      prioritization. The fundamentals of Metabolic Control Analysis (MCA; an approach
      in the study of control and regulation of metabolism) and kinetic modeling of
      metabolic pathways (a bottom-up systems biology approach) allow quantification of
      the degree of control that each enzyme exerts on the pathway flux (flux control
      coefficient) and metabolic intermediate concentrations (concentration control
      coefficient). MCA studies have demonstrated that metabolic pathways usually have
      two or three enzymes with the highest control of flux; their inhibition has more
      negative effects on the pathway function than inhibition of enzymes exerting low
      flux control. Therefore, the enzymes with the highest pathway control are the
      most convenient targets for therapeutic intervention. In this review, the
      fundamentals of MCA as well as experimental strategies to determine the flux
      control coefficients and metabolic modeling are analyzed. MCA and kinetic
      modeling have been applied to trypanothione metabolism in Trypanosoma cruzi and
      the model predictions subsequently validated in vivo. The results showed that
      three out of ten enzyme reactions analyzed in the T. cruzi anti-oxidant
      metabolism were the most controlling enzymes. Hence, MCA and metabolic modeling
      allow a further step in target prioritization for drug development against
      trypanosomatids and other parasites.

PMID- 30221600
TI  - Ocular Ciliopathies: genetic and mechanistic insights into developing therapies.
AB  - Developing suitable medicines for genetic diseases requires a detailed
      understanding of not only the pathways that cause the disease, but also the
      identification of the genetic components involved in disease manifestation. This
      article focuses on the complexities associated with ocular ciliopathies - a class
      of debilitating disorders of the eye caused by ciliary dysfunction. Ciliated cell
      types have been identified in both the anterior and posterior segments of the
      eye. Photoreceptors (rods and cones) are the most studied ciliated neurons in the
      retina, which is located in the posterior eye. The photoreceptors contain a
      specialized light-sensing outer segment, or cilium. Any defects in the
      development or maintenance of the outer segment can result in severe retinal
      ciliopathies, such as retinitis pigmentosa and Leber congenital amaurosis. A role
      of cilia in the cell types involved in regulating aqueous fluid outflow in the
      anterior segment of the eye has also been recognized. Defects in these cell types
      are frequently associated with some forms of glaucoma. Here, we will discuss the
      significance of understanding the genetic heterogeneity and the pathogenesis of
      ocular ciliopathies to develop suitable treatment strategies for these blinding
      disorders.

PMID- 30221602
TI  - A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer
      Properties.
AB  - BACKGROUND: Cancer is a major cause of death worldwide, despite many different
      drugs available to treat the disease. This high mortality rate is largely due to
      the complexity of the disease, which results from several genetic and epigenetic
      changes. Therefore, researchers are constantly searching for novel drugs that can
      target different and multiple aspects of cancer. EXPERIMENTAL: After a screening,
      we selected one novel molecule, out of ninety-four triazole derivatives, that
      strongly affects the viability and proliferation of the human breast cancer cell
      line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94,
      induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2
      +/- 0.2 uM. Additionally, DAN94 interfered with mitochondria metabolism promoting
      reactive oxygen species production, triggering apoptosis and arresting the cancer
      cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects
      are not observed when the drug was tested in the non-cancer cell line MCF10A.
      Using a mouse model with xenograft tumor implants, the drug preventing tumor
      growth presented no toxicity for the animal and without altering biochemical
      markers of hepatic function. RESULTS AND CONCLUSION: The novel drug DAN94 is
      selective for cancer cells, targeting the mitochondrial metabolism, which
      culminates in the cancer cell death. In the end, DAN94 has been shown to be a
      promising drug for controlling breast cancer with minimal undesirable effects.

PMID- 30221603
TI  - Immune-mediated cerebellar ataxias: Practical guidelines and therapeutic
      challenges.
AB  - Immune-mediated cerebellar ataxias (IMCAs), a clinical entity reported for the
      first time in the 1980s, include gluten ataxia (GA), paraneoplastic cerebellar
      degenerations (PCDs), anti-glutamate decarboxylase 65 (GAD) antibody-associated
      cerebellar ataxia, post-infectious cerebellitis, and opsoclonus myoclonus
      syndrome (OMS). These IMCAs share common features with regard to therapeutic
      approaches. When certain factors trigger immune processes, elimination of the
      antigen(s) becomes a priority: e.g., gluten-free diet in GA and surgical excision
      of the primary tumor in PCDs. Furthermore, various immunotherapeutic modalities
      (e.g., steroids, immunoglobulins, plasmapheresis, immunosuppressants, rituximab)
      should be considered alone or in combination to prevent the progression of the
      IMCAs. There is no evidence of significant differences in terms of response and
      prognosis among the various types of immunotherapies. Treatment introduced at an
      early stage, when CAs or cerebellar atrophy is mild, is associated with better
      prognosis. Preservation of the "cerebellar reserve" is necessary for improvement
      of CAs and resilience of the cerebellar networks. In this regard, we emphasize
      the therapeutic principle of "Time is Cerebellum" in IMCAs.

PMID- 30221604
TI  - Stiff left atrial syndrome; prospects and possibilities. Retrospective analysis
      and review of the literature.
AB  - OBJECTIVES: Stiff left atrial syndrome is an intriguing clinical phenomena
      characterized by reduced left atrial compliance, pulmonary venous hypertension
      and exacerbations of volume overload. We conducted a retrospective review of
      patients diagnosed with stiff left atrial syndrome at our center. METHODS: All
      patients admitted to our hospital with volume overload and pulmonary venous
      hypertension who were diagnosed with stiff left atrial syndrome based on evidence
      by echocardiogram and right heart catheterization between July 2011 and July 2013
      were included in this retrospective review. RESULTS: Twenty three patients (mean
      age 73 +/- 11 years, 39% male and 61% female) were diagnosed with stiff left
      atrial syndrome at our center. Thirty-five percent had persistent while 39% had
      permanent atrial fibrillation. Mean duration of atrial fibrillation was 7.6 +/-
      2.1 years. Forty-three percent of patients had long standing hypertension. There
      was no mitral regurgitation in 39% of patients while 48% had mild mitral
      regurgitation. On right heart catheterization, mean right atrial pressure was
      12.6+/-4.8 mm of Hg, mean pulmonary arterial pressure was 33+/-7.2 mm of Hg, mean
      pulmonary capillary wedge pressure was 24.8+/- 4.2mm of Hg while peak V waves
      were seen at mean of 37.8+/- 5.3 mm of Hg. Mean left atrial volume index was
      49.8+/-17.1 mL/m 2. After the initial diagnosis with a two year follow- up, there
      were no readmissions in 65% of patients who were on appropriate diuretic therapy
      and had regular clinical visits. Frequent readmissions were seen in 35% of
      patients inspite of appropriate diuretic therapy. All-cause mortality rate was
      4.3% at two year follow up. CONCLUSIONS: In patients with stiff left atrial
      syndrome, the presence of left atrial dilation, long standing atrial fibrillation
      and hypertension are the key factors associated with pathogenesis and clinical
      course. Close follow up and monitoring of volume status is essential to prevent
      hospital readmissions and improve long term prognosis.

PMID- 30221605
TI  - Clinical and Serological Biomarkers of Treatment's Response in Multiple Sclerosis
      Patients Treated Continuously with Interferonbeta-1b for More than a Decade.
AB  - INTRODUCTION: We evaluated the peripheral immune panel of Multiple Sclerosis (MS)
      patients treated for more than 10 years with interferon-beta1b (IFNbeta-1b) and
      aimed to identify possible biomarkers of treatment response. MATERIAL AND
      METHODS: Serum samples from 70 MS patients treated with IFNbeta-1b more than a
      decade were analysed for 15 cytokines, that were correlated with the disability
      score, annual relapse ratio (ARR): the total number of relapses-ARR_0, relapse on
      treatment-ARR_1 and demographic data. Two groups were defined based on the levels
      of disability, calculated using the Expanded Disability Status Scale (EDSS): G1 -
      recurrent-remissive and G2 - secondary-progressive. Furthermore, we split the
      patients based on gender (G1_f, G1_m, G2_f, G2_m). RESULTS: The ARR was reduced
      after treatment was instituted. We found positive correlations between IL_25 and
      EDSS in G1_f and G2_f, tumor necrosis factor alpha (TNFalpha) and ARR_1 and ARR_0
      in G1, and IL_17F with ARR_1. Negative correlations were for IL_25 and ARR_0 and
      ARR_1. SCD40L intensely positively correlated with IL_31 in G1 and G2.
      CONCLUSION: After more than a decade of treatment, IFNbeta-1b offers good results
      by reducing relapses and slowing disability progression. Several biomarkers can
      be used to assess the patient's response. High levels of IL_17 and TNFalpha will
      indicate a more active form of the disease. IL-25 may exert a positive influence
      in male MS patients and should be considered for future studies, together with
      the co-modulation between sCD40L and IL_31. Our method allowed us to screen the
      peripheral immune panel and can be used for assessing the peripheral levels of
      the above-mentioned cytokines.

PMID- 30221606
TI  - Optimization of process parameters for production of pectinase using Bacillus
      Subtilis MF447840.1.
AB  - BACKGROUND: Pectinase enzyme has immense industrial prospects in food and
      beverage industries. We mentioned the patents relating to pectinase used in
      various industries. OBJECTIVE: In this study, the optimization of the process
      parameters for the pectinase production was carried out from Bacillus Subtilis
      MF447840.1 using submerged fermentation. METHOD: 2% (OD600 nm=0.1) of seed
      culture was inoculated in production media. The production media components used
      for this study was 1 g/l of pectin, 0.5 g/l of sodium chloride, 0.75 g of K2HPO4
      , 0.25 gm of KH2PO4 and 0.5 g/l of magnesium sulphate for pectinase production.
      The various process parameters were optimized by changed one variable time
      method. RESULTS: The optimum process parameters were found to be inoculums
      percentage (5%), volume ratio percentage (25%), temperature (37  degrees C), pH
      (7.4) and agitation (120 rpm) after 4 days fermentation. CONCLUSION: Maximum
      pectinase production was found to be 345+/-12.35 U after 4 days fermentation.

PMID- 30221607
TI  - An efficient classification algorithm for NGS data based on text similarity.
AB  - With the advancement of high-throughput sequencing technologies, the amount of
      available sequencing data is growing at a pace that has now begun to greatly
      challenge the data processing and storage capacities of modern computer systems.
      Removing redundancy from such data by clustering could be crucial for reducing
      memory, disk space and running time consumption. In addition, it also has good
      performance on reducing dataset noise in some analysis applications. In this
      study, we propose a high-performance short sequence classification algorithm
      (HSC) for next generation sequencing (NGS) data based on efficient hash function
      and text similarity. First, HSC converts all reads into k-mers, then it forms a
      unique k-mer set by merging the duplicated and reverse complementary elements.
      Second, all unique k-mers are stored in a hash table, where the k-mer string is
      stored in the key field, and the ID of the reads containing the k-mer are stored
      in the value field. Third, each hash unit is transformed into a short text
      consisting of reads. Fourth, texts that satisfy the similarity threshold are
      combined into a long text, the merge operation is executed iteratively until
      there is no text that satisfies the merge condition. Finally, the long text is
      transformed into a cluster consisting of reads. We tested HSC using five real
      datasets. The experimental results showed that HSC cluster 100 million short
      reads within 2 hours, and it has excellent performance in reducing memory
      consumption. Compared to existing methods, HSC is much faster than other tools,
      it can easily handle tens of millions of sequences. In addition, when HSC is used
      as a preprocessing tool to produce assembly data, the memory and time consumption
      of the assembler is greatly reduced. It can help the assembler to achieve better
      assemblies in terms of N50, NA50 and genome fraction.

PMID- 30221608
TI  - Vascular ring associated with d-transposition of the great arteries: when should
      we suspect aortic arch anomalies?
AB  - A male neonate with d-transposition of the great arteries was diagnosed with the
      concomitant anomaly of left circumflex aortic arch and right-sided ductus
      arteriosus, which formed a vascular ring. Initial postnatal echocardiography had
      demonstrated an obscured aortic isthmus mimicking coarctation of the aorta, which
      could be a diagnostic clue to circumflex aortic arch.

PMID- 30221609
TI  - Application of a fluorescent marker with quantitative bioburden methods to assess
      cleanliness.
AB  - BACKGROUND: Improvement of environmental cleaning in hospitals has been shown to
      decrease in-hospital cross transmission of pathogens. Several objective methods,
      including aerobic colony counts (ACCs), the adenosine triphosphate (ATP)
      bioluminescence assay, and the fluorescent marker method have been developed to
      assess cleanliness. However, the standard interpretation of cleanliness using the
      fluorescent marker method remains uncertain. OBJECTIVE: To assess the fluorescent
      marker method as a tool for determining the effectiveness of hospital cleaning.
      DESIGN: A prospective survey study. SETTING: An academic medical center. METHODS:
      The same 10 high-touch surfaces were tested after each terminal cleaning using
      (1) the fluorescent marker method, (2) the ATP assay, and (3) the ACC method.
      Using the fluorescent marker method under study, surfaces were classified as
      totally clean, partially clean, or not clean. The ACC method was used as the
      standard for comparison. RESULTS: According to the fluorescent marker method, of
      the 830 high-touch surfaces, 321 surfaces (38.7%) were totally clean (TC group),
      84 surfaces (10.1%) were partially clean (PC group), and 425 surfaces (51.2%)
      were not clean (NC group). The TC group had significantly lower ATP and ACC
      values (mean +/- SD, 428.7 +/- 1,180.0 relative light units [RLU] and 15.6 +/-
      77.3 colony forming units [CFU]/100 cm2) than the PC group (1,386.8 +/- 2,434.0
      RLU and 34.9 +/- 87.2 CFU/100 cm2) and the NC group (1,132.9 +/- 2,976.1 RLU and
      46.8 +/- 119.2 CFU/100 cm2). CONCLUSIONS: The fluorescent marker method provided
      a simple, reliable, and real-time assessment of environmental cleaning in
      hospitals. Our results indicate that only a surface determined to be totally
      clean using the fluorescent marker method could be considered clean.

PMID- 30221610
TI  - Genetic influences on eight psychiatric disorders based on family data of 4 408
      646 full and half-siblings, and genetic data of 333 748 cases and controls.
AB  - BACKGROUND: Most studies underline the contribution of heritable factors for
      psychiatric disorders. However, heritability estimates depend on the population
      under study, diagnostic instruments, and study designs that each has its inherent
      assumptions, strengths, and biases. We aim to test the homogeneity in
      heritability estimates between two powerful, and state of the art study designs
      for eight psychiatric disorders. METHODS: We assessed heritability based on data
      of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on
      summary data of eight samples with measured genotypes (N = 125 533 cases and 208
      215 controls). All data were based on standard diagnostic criteria. Eight
      psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia
      nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum
      disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive
      compulsive disorder (OCD), and (8) schizophrenia. RESULTS: Heritability estimates
      from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The
      estimates based on the measured genotypes were lower, ranging from 0.10 for AD to
      0.28 for OCD, but were significant, and correlated positively (0.19) with
      national sibling-based estimates. When removing OCD from the data the correlation
      increased to 0.50. CONCLUSIONS: Given the unique character of each study design,
      the convergent findings for these eight psychiatric conditions suggest that
      heritability estimates are robust across different methods. The findings also
      highlight large differences in genetic and environmental influences between
      psychiatric disorders, providing future directions for etiological psychiatric
      research.

PMID- 30221611
TI  - Timing of post-resistance exercise nutrient ingestion: effects on gastric
      emptying and glucose and amino acid responses in humans.
AB  - This study examined the effects of post-resistance exercise protein ingestion
      timing on the rate of gastric emptying (GE) and blood glucose (BG) and plasma
      branched-chain amino acid (BCAA) responses. In all, eleven healthy participants
      randomly ingested 400 ml of a nutrient-rich drink containing 12 g carbohydrates
      and 20 g protein at rest (Con), at 5 min (post-exercise (PE)-5) or at 30 min (PE
      30) after a single bout of strenuous resistance exercises. The first and second
      sets comprised ten repetitions at 50 % of each participant's one-repetition
      maximum (1RM). The third, fourth and fifth sets comprised ten repetitions at 75 %
      of 1RM, and the sixth set involved repeated repetitions until exhaustion.
      Following ingestion of the nutrient-rich drink, we assessed the GE rate using 13C
      sodium acetate breath test and evaluated two parameters according to the T max
      calc (time when the recovery per hour is maximised), which is a standard
      analytical method, and T 1/2 (time when the total cumulative dose of [13CO2]
      reaches one-half). T max-calc and T 1/2 were slower for the PE-5 condition than
      for either the PE-30 or Con condition (T max-calc; Con: 53 (sd 7) min, PE-5: 83
      (sd 16) min, PE-30: 62 (sd 9) min, T 1/2; Con: 91 (sd 7) min, PE-5: 113 (sd 21)
      min, PE-30: 91 (sd 11) min, P<0.05). BG and BCAA responses were also slower for
      the PE-5 condition than for either the PE-30 or Con condition. Ingesting
      nutrients immediately after strenuous resistance exercise acutely delayed GE,
      which affected BG and plasma BCAA levels in blood circulation.

PMID- 30221612
TI  - Review and update of the Health of the Nation Outcome Scales for Elderly People
      (HoNOS65+).
AB  - Aims and methodThe Health of the Nation Outcome Scales for Elderly People
      (HoNOS65+) has been used widely for 20 years, but has not been updated to reflect
      contemporary clinical practice. The Royal College of Psychiatrists convened an
      advisory board, with expertise from the UK, Australia and New Zealand, to propose
      amendments. The aim was to improve rater experience when using the HoNOS65+
      glossary by removing ambiguity and inconsistency, rather than a more radical
      revision. RESULTS: Views and experience from the countries involved were used to
      produce a series of amendments intended to improve intra- and interrater
      reliability and improve validity. This update will be called HoNOS Older Adults
      to reflect the changing nature of the population and services provided to meet
      their needs. These improvements are reported verbatim, together with the original
      HoNOS65+ to aid comparison.Clinical implicationsFormal examination of the
      psychometric properties of the revised measure is needed. However, clinician
      training will remain crucial.Declaration of interestNone.

PMID- 30221613
TI  - Preventable hospitalizations among older patients with cognitive impairments and
      dementia.
AB  - : ABSTRACTObjectives:Dementia and cognitive impairment are associated with higher
      rates of complications and mortality during hospitalization in older patients.
      Moreover, length of hospital stay and costs are increased. In this prospective
      cohort study, we investigated the frequency of hospitalizations caused by
      ambulatory care-sensitive conditions (ACSCs), for which proactive ambulatory care
      might prevent the need for a hospital stay, in older patients with and without
      cognitive impairments. DESIGN: Prospective cohort study. SETTING: Eight hospitals
      in Germany. PARTICIPANTS: A total of 1,320 patients aged 70 years and older.
      MEASUREMENTS: The Mini-Cog test has been used to assess cognition and to
      categorize patients in the groups no/moderate cognitive impairments (probably no
      dementia) and severe cognitive impairments (probable dementia). Moreover, lengths
      of hospital stay and complication rates have been assessed, using a binary
      questionnaire (if occurred during hospital stay or not; behavioral symptoms were
      adapted from the Cohen-Mansfield Agitation Inventory). Data have been acquired by
      the nursing staff who received a special multi-day training. RESULTS: Patients
      with severe cognitive impairments showed higher complication rates (including
      incontinence, disorientation, irritability/aggression, restlessness/anxiety,
      necessity of Tranquilizers and psychiatric consults, application of measures
      limiting freedom, and falls) and longer hospital stays (+1.4 days) than patients
      with no/moderate cognitive impairments. Both groups showed comparably high ACSC
      caused admission rates of around 23%. CONCLUSIONS: The study indicates that about
      one-fourth of hospital admissions of cognitively normal and impaired older adults
      are caused by ACSCs, which are mostly treatable on an ambulatory basis. This
      implies that an improved ambulatory care might reduce the frequency of
      hospitalizations, which is of particular importance in cognitively impaired
      elderly due to increased complication rates.

PMID- 30221614
TI  - Street triage services in England: service models, national provision and the
      opinions of police.
AB  - Aims and methodStreet triage services are increasingly common and part of
      standard responses to mental health crises in the community, but little is
      understood about them. We conducted a national survey of mental health trusts to
      gather detailed information regarding street triage services alongside a survey
      of Thames Valley police officers to ascertain their views and experiences.
      RESULTS: Triage services are available in most areas of the country and are
      growing in scope. There is wide variation in levels of funding and modes of
      operation, including hours covered. Police officers from our survey
      overwhelmingly support such services and would like to see them expanded.Clinical
      implicationsMental health crises now form a core part of policing and there are
      compelling reasons for the support of specialist services. Recent changes to the
      law have heightened this need, with a requirement for specialist input before a
      Section 136 is enacted. Those who have experienced triage services report it as
      less stigmatising and traumatic than a traditional approach, but there remains
      little evidence on which to base decisions.Declaration of interestNone.

PMID- 30221615
TI  - DREAMS-START (Dementia RElAted Manual for Sleep; STrAtegies for RelaTives) for
      people with dementia and sleep disturbances: a single-blind feasibility and
      acceptability randomized controlled trial.
AB  - : ABSTRACTBackground:40% of people with dementia have disturbed sleep but there
      are currently no known effective treatments. Studies of sleep hygiene and light
      therapy have not been powered to indicate feasibility and acceptability and have
      shown 40-50% retention. We tested the feasibility and acceptability of a six
      session manualized evidence-based non-pharmacological therapy; Dementia RElAted
      Manual for Sleep; STrAtegies for RelaTives (DREAMS-START) for sleep disturbance
      in people with dementia. METHODS: We conducted a parallel, two-armed, single
      blind randomized trial and randomized 2:1 to intervention: Treatment as Usual.
      Eligible participants had dementia and sleep disturbances (scoring >=4 on one
      Sleep Disorders Inventory item) and a family carer and were recruited from two
      London memory services and Join Dementia Research. Participants wore an actiwatch
      for two weeks pre-randomization. Trained, clinically supervised psychology
      graduates delivered DREAMS-START to carers randomized to intervention; covering
      Understanding sleep and dementia; Making a plan (incorporating actiwatch
      information, light exposure using a light box); Daytime activity and routine;
      Difficult night-time behaviors; Taking care of your own (carer's) sleep; and What
      works? Strategies for the future. Carers kept their manual, light box, and
      relaxation recordings post-intervention. Outcome assessment was masked to
      allocation. The co-primary outcomes were feasibility (>=50% eligible people
      consenting to the study) and acceptability (>=75% of intervention group attending
      >=4 intervention sessions). RESULTS: In total, 63out of 95 (66%; 95% CI: 56-76%)
      eligible referrals consented between 04/08/2016 and 24/03/2017; 62 (65%; 95% CI:
      55-75%) were randomized, and 37 out of 42 (88%; 95% CI: 75-96%) adhered to the
      intervention. CONCLUSIONS: DREAM-START for sleep disorders in dementia is
      feasible and acceptable.

PMID- 30221616
TI  - Coronary artery occlusion secondary to graft versus host disease after bone
      marrow transplant in a 21-year-old.
AB  - Coronary artery disease after bone marrow transplantation is rare in children and
      young adults. We report the case of a 21-year-old who developed coronary artery
      disease and acute myocardial infarction secondary to graft versus host disease
      following bone marrow transplantation. Physicians caring for young patients after
      bone marrow transplantation should be aware of the potential for coronary artery
      disease and evaluate appropriately.

PMID- 30221617
TI  - Purulent pericarditis secondary to influenza and community-acquired methicillin
      resistant Staphylococcus aureus co-infection.
AB  - Purulent pericarditis occurs rarely in the current antibiotic era. We describe
      clinical and echocardiographic features of purulent pericarditis in a previously
      healthy child with influenza and community-acquired methicillin-resistant
      Staphylococcus aureus co-infection. The child was already on appropriate
      antibiotics and had a very subtle clinical presentation, with prominent abdominal
      symptoms. Timely surgical drainage led to complete recovery.

PMID- 30221619
TI  - Brief cognitive-behavioural therapy for patients in the community with
      schizophrenia: Randomised controlled trial in Beijing, China - Expression of
      Concern.

PMID- 30221618
TI  - Incidence of abdominal obesity and its risk factors among Tehranian adults.
AB  - OBJECTIVE: Abdominal obesity (AO) is a relative risk factor for cardiovascular
      events. We aimed to determine the 6-year incidence of AO and its risk factors
      among Tehranian adults.Design/Setting/SubjectsIn this population-based cohort
      study, non-abdominally obese participants, aged >=20 years, were followed for
      incidence of AO. Cumulative incidence and incidence rate of AO were calculated
      for each sex. Cox proportional hazard regression was used to determine the
      association of potential risk factors including age, BMI, dysmetabolic state,
      smoking, marital status, educational level and physical activity (PA). RESULTS: A
      total of 5044 participants (1912 men) were followed for a median of 6 years. Mean
      age was 37.7 (sd 13.5) years at baseline, with mean BMI of 24.3 (sd 3.1) kg/m2
      (men, 23.0 (sd 2.4) kg/m2; women, 25.0 (sd 3.2) kg/m2). During follow-up, 3093
      (1373 men) developed AO with total cumulative incidence of 76.02, 83.59 and 70.90
      %, for the whole population, men and women, respectively. Corresponding incidence
      rates were 96.0, 138.7 and 77.1 per 1000 person-years. The highest incidence rate
      was observed during their 30s and 50s, in men and women, respectively. Subjects
      with dysmetabolic state in both sexes, married women, men with lower PA and
      higher educational levels at baseline were at higher risk of AO. CONCLUSIONS: The
      incidence of AO is high among Tehranian adults, especially in young men. The risk
      factors for developing AO should be highlighted to halt this growing trend of AO.

PMID- 30221620
TI  - A multi-group approach to examining language development in at-risk learners.
AB  - A battery of standardized language tests and control measures was administered to
      three groups of at-risk language learners - internationally adopted children,
      deaf children with cochlear implants, and children with specific language
      impairment - and to groups of second-language learners and typically developing
      monolingual children. All children were acquiring French, were matched on age,
      gender, and socioeconomic status, and were between age 5;0 and 7;3 at the time of
      testing. Differences between the at-risk and not-at-risk groups were evident in
      all domains of language testing. The children with SLI or CIs scored
      significantly lower than the IA children and all three at-risk groups scored
      lower than the monolingual group; the L2 and IA groups scored similarly. The
      results suggest that children with limited access to, or ability to process,
      early language input are at greater risk than children with delayed input to an
      additional language but otherwise typical or relatively typical early input.

PMID- 30221621
TI  - Facility infrastructure of primary health services regarding tuberculosis
      control: a countrywide cross-sectional study.
AB  - BACKGROUND: Tuberculosis (TB) is still a major public health problem in many
      countries, including Brazil. Primary health care (PHC) services are a set of
      important services with infrastructure and resources to diagnose, treat, and cure
      several diseases, including the TB.AimThe aim of this study is to analyse aspects
      of the facility infrastructure of Brazilian PHC, regarding the control and
      treatment of TB from a countrywide perspective. METHODS: This is a cross
      sectional study based on PHC services. Data were collected from 38,812 health
      centres and were assessed by means of the National Program for Improving Access
      and Quality Primary Care. The outcome was obtained by the presence and
      availability of the following infrastructure items: air circulation in the
      consultation room, refrigerator, individual protective equipment, plastic jar for
      sputum examination, and TB notification form of the primary care information
      system. Poisson regression was used to calculate the prevalence ratio.FindingsOf
      the 38,812 evaluated centres, only 1628 (4.2%) presented a positive result
      regarding the outcome. Primary health centres, among all types of centres,
      presented the highest quality of facility infrastructure for TB control. Centres
      with large workloads, as well as those that presented a list of offered services
      and a welcoming consulting room, also presented the highest quality
      infrastructure. The present study shows that major improvements should be made to
      the infrastructure to reach a satisfactory TB control in Brazil.

PMID- 30221623
TI  - Luminescence light collection technology in the aragonite of stone corals.
AB  - Stone corals do not use calcium carbonate in the form of calcite, which has a
      calculated energy gap of 3.93 eV, but in the form of aragonite, which has a
      calculated energy gap of 2.88 eV (here experimentally determined to amount to
      2.46 eV) as a building material. This enables the coral to harvest blue light,
      which is penetrating and filtering deep into the surface water of the ocean.
      White luminescence, which is composed of different wave lengths, is generated,
      and then conducted and redistributed within the aragonite structure to be
      supplied to the symbiotic photosynthetic algae. This mechanism of light
      concentration and adaptation via the aragonite structure leads to a smaller
      amount of light-absorbing phosphorescent pigments being required for the
      symbionts to survive. The resulting advantages are a significantly smaller
      exposure to photo-degradation, less effort for chemical synthesis and higher
      efficiency for solar energy conversion. The mechanism of luminescence light
      collection in the aragonite network is discussed on the basis of spectroscopic
      measurements on thin coral slices and in context with its architecture and the
      coral's living activities. The relevance of the stone coral's fractal geometry,
      both for broadband solar light harvesting and luminescence light collection
      within non-imaging optics, is emphasized. It is proposed that synthetic aragonite
      should be developed as a solar energy material.

PMID- 30221624
TI  - A control-theoretic system identification framework and a real-time closed-loop
      clinical simulation testbed for electrical brain stimulation.
AB  - OBJECTIVE: Closed-loop electrical brain stimulation systems may enable a
      precisely-tailored treatment for neurological and neuropsychiatric disorders by
      controlling the stimulation based on neural activity feedback in real time.
      Developing model-based closed-loop systems requires a principled system
      identification framework to quantify the effect of input stimulation on output
      neural activity by learning an input-output (IO) dynamic model from data.
      Further, developing these systems needs a realistic clinical simulation testbed
      to design and validate the closed-loop controllers derived from the IO models
      before testing in human patients. APPROACH: First, we design a control-theoretic
      system identification framework to build dynamic IO models for neural activity
      that are amenable to closed-loop control design. To enable tractable model-based
      control, we use a data-driven linear state-space IO model that characterizes the
      effect of input on neural activity in terms of a low-dimensional hidden neural
      state. To learn the model parameters, we design a novel input waveform-a pulse
      train modulated by stochastic binary noise (BN) parameters-that we show is
      optimal for collecting informative IO datasets in system identification and
      conforms to clinical safety requirements. Second, we further extend this waveform
      to a generalized BN (GBN)-modulated waveform to reduce the required system
      identification time. Third, to enable extensive testing of system identification
      and closed-loop control, we develop a real-time closed-loop clinical hardware-in
      the-loop (HIL) simulation testbed using the [Formula: see text] microelectrode
      recording and stimulation device, which incorporates stochastic noises, unknown
      disturbances and stimulation artifacts. Using this testbed, we implement both the
      system identification and the closed-loop controller by taking control of mood in
      depression as an example. RESULTS: Testbed simulation results show that the
      closed-loop controller designed from IO models identified with the BN-modulated
      waveform achieves tight control, and performs similar to a controller that knows
      the true IO model of neural activity. When system identification time is limited,
      performance is further improved using the GBN-modulated waveform. SIGNIFICANCE:
      The system identification framework with the new BN-modulated waveform and the
      clinical HIL simulation testbed can help develop future model-based closed-loop
      electrical brain stimulation systems for treatment of neurological and
      neuropsychiatric disorders.

PMID- 30221625
TI  - Hebbian learning for online prediction, neural recall and classical conditioning
      of anthropomimetic robot arm motions.
AB  - Classical conditioning plays a vital role in learning in every mammal. It is
      based on unsupervised neural learning embodied in a physical body that is in
      continuous interaction with the environment. Embedding the hierarchical temporal
      memory (HTM) in the closed loop of the sensorimotor space of a Myorobotics tendon
      driven robotic arm we demonstrate learning, prediction and control of biomimetic
      body motions. Experiments finally lead to conditioned reactions in natural
      interaction with a human partner. The HTM is able to learn arm movements
      generated by interaction with a human partner in a short time. It predicts future
      positions in different time scales up to seconds in advance. Closing the loop we
      utilize HTM predictions for motor control. Hereby learned motions are recalled
      from synaptic connections proactively continuing motion execution. Association,
      prediction and control are required by the HTM for conditioning according to
      Pavlov: neutral stimuli get associated with motions, and after learning sensor
      impulses can trigger single arm lifting motions. Hereby, both the motions and the
      stimuli are learned from the environment and get associated efficiently. We can
      demonstrate high biological plausibility as for example even input variations
      result in similar variations in the action output. The robotic system consisting
      of biologically-derived hardware and software components utilizes only
      unsupervised Hebbian learning to act autonomously. Learning is executed in real
      time, can handle natural variations of human motions and takes morphologically
      plausible sensor input into account. The setup is fully scalable due to its
      modularity. Hereby, novel applications for the HTM are opened: it can be used in
      musculoskeletal robot control scenarios and robots being able to interactively
      learn from human partners and the environment.

PMID- 30221622
TI  - Intravoxel incoherent motion MRI in neurological and cerebrovascular diseases.
AB  - Intravoxel Incoherent Motion (IVIM) is a recently rediscovered noninvasive
      magnetic resonance imaging (MRI) method based on diffusion-weighted imaging. It
      enables the separation of the intravoxel signal into diffusion due to Brownian
      motion and perfusion-related contributions and provides important information on
      microperfusion in the tissue and therefore it is a promising tool for
      applications in neurological and neurovascular diseases. This review focuses on
      the basic principles and outputs of IVIM and details it major applications in the
      brain, such as stroke, tumor, and cerebral small vessel disease. A bi-exponential
      model that considers two different compartments, namely capillaries, and medium
      sized vessels, has been frequently used for the description of the IVIM signal
      and may be important in those clinical applications cited before. Moreover, the
      combination of IVIM and arterial spin labeling MRI enables the estimation of
      water permeability across the blood-brain barrier (BBB), suggesting a potential
      imaging biomarker for disrupted-BBB diseases.

PMID- 30221626
TI  - A novel system of SSVEP-based human-robot coordination.
AB  - OBJECTIVE: Human-robot coordination (HRC) aims to enable human and robot to form
      a tightly coupled system to accomplish a task. One of its important application
      prospects is to improve the physical function of the disabled. However, the low
      level of the coordination between human and robot and the limited potential users
      still hamper the efficiency of such systems. APPROACH: To deal with such
      challenges, a novel steady-state visual evoked potential (SSVEP) based human
      robot coordinated brain-computer interface (BCI) system was proposed to finish a
      target capturing task. In this system, the robot, by combining the information
      obtained during the human's natural interaction with itself to capture a target,
      could optimize the same object capturing task and yield a better performance
      automatically. The combination of human dealing with the uncertainty problem and
      the robot dealing with the complexity problem was the key to the system.
      Meanwhile, an asynchronous BCI based on SSVEP was used as the system interface,
      and a novel asynchronous recognition algorithm was used to discriminate the
      electroencephalogram (EEG) signal. MAIN RESULTS: The results show that the
      proposed system can lower the fatigue level of the subject and simplify the
      operation of the system. Meanwhile, the signal recognition accuracy and the
      efficiency of the system were also improved. SIGNIFICANCE: Under the help of the
      close and natural coordination relationship design between human and robot, and
      the asynchronous SSVEP based BCI design which requires no limb movement to
      control a robot, the users would be provided with an accurate and efficient
      control experience. Moreover, people with severe motor diseases might potentially
      benefit from such a system. Also, the proposed methods can be easily integrated
      into other BCI diagrams, which would ameliorate the predicament of the HRC.

PMID- 30221627
TI  - Cone-beam CT reconstruction with gravity-induced motion.
AB  - Fixed-gantry cone-beam computed tomography (CBCT), where the imaging hardware is
      fixed while the subject is continuously rotated 360 degrees  in the horizontal
      position, has implications for building compact and affordable fixed-gantry
      linear accelerators (linacs). Fixed-gantry imaging with a rotating subject
      presents a challenging image reconstruction problem where the gravity-induced
      motion is coupled to the subject's rotation angle. This study is the first to
      investigate the feasibility of fixed-gantry CBCT using imaging data of three live
      rabbits in an ethics-approved study. A novel data-driven motion correction method
      that combines partial-view reconstruction and motion compensation was developed
      to overcome this challenge. Fixed-gantry CBCT scans of three live rabbits were
      acquired on a standard radiotherapy system with the imaging beam fixed and the
      rabbits continuously rotated using an in-house programmable rotation cradle. The
      reconstructed images of the thoracic region were validated against conventional
      CBCT scans acquired at different cradle rotation angles. Results showed that
      gravity-induced motion caused severe motion blur in all of the cases if
      unaccounted for. The proposed motion correction method yielded clinically usable
      image quality with  <1 mm gravity-induced motion blur for rabbits that were
      securely immobilized on the rotation cradle. Shapes of the anatomic structures
      were correctly reconstructed with  <0.5 mm accuracy. Translational motion
      accounted for the majority of gravity-induced motion. The motion-corrected
      reconstruction represented the time-averaged location of the thoracic region over
      a 360 degrees  rotation. The feasibility of fixed-gantry CBCT has been
      demonstrated. Future work involves the validation of imaging accuracy for human
      subjects, which will be useful for emerging compact fixed-gantry radiotherapy
      systems.

PMID- 30221628
TI  - Control of a muscle-like soft actuator via a bioinspired approach.
AB  - Soft actuators have played an indispensable role in generating compliant motions
      of soft robots. Among the various soft actuators explored for soft robotic
      applications, dielectric elastomer actuators (DEAs) have caught the eye with
      their intriguing attributes similar to biological muscles. However, the control
      challenge of DEAs due to their strong nonlinear behaviors has hindered the
      development of DEA-based soft robots. To overcome the control challenge, this
      paper proposes a bioinspired control approach of DEAs. A three-dimensional muscle
      like DEA, capable of large forces and giant deformation, is fabricated and
      adopted as the control platform. To facilitate the controller design, the dynamic
      model of the DEA is developed through experimental analysis, which takes
      electromechanical coupling, viscoelastic effects and dynamics uncertainties into
      consideration. Motivated by the proprioception of the biological muscles, the
      self-sensing capability of the actuator is explored and exhibits good accuracy.
      Thus the self-sensing of the actuator is utilized to provide the sensory feedback
      in the control loop without the need of additional external sensors. Inspired
      from the role of the cerebellum in motor learning, a cerebellum model
      articulation nonlinear controller is proposed to compensate the dynamics
      uncertainties and to provide motion correction. Finally, the effectiveness of the
      proposed control approach is verified by both the simulation and the experiments.

PMID- 30221629
TI  - Detection of lung cancer with electronic nose and logistic regression analysis.
AB  - Lung cancer is a very common malignancy with a low five-year survival rate.
      Artificial olfactory sensor (electronic nose) is a tool that recently has been
      studied as a probable optimal screening tool for early detection of lung cancer,
      but still no statistical method has been put forward as the preferable one. The
      aim of the study was to explore the use of logistic regression analysis (LRA) to
      analyse patients' exhaled breath samples with electronic nose in order to
      differentiate lung cancer patients (regardless of the stage of the cancer) from
      patients with other lung diseases and healthy individuals. Patients with
      histologically or cytologically verified, untreated lung cancer, patients with
      other lung diseases such as benign lung tumors, chronic obstructive pulmonary
      disease, asthma, pneumonia, etc, and healthy volunteers were enrolled in the
      study, in total 252 cancer patients and 223 patients without cancer. Breath
      sample collection and analysis were performed with Cyranose 320 sensor device and
      data further analysed using LRA. The LRA correctly differentiated lung cancer
      patients from no-cancer patients. The overall sensitivity in detecting patients
      having cancer was 95.8% for smokers and 96.2% for non-smokers and the overall
      specificity was 90.6% for non-smokers and 92.3% for smokers. Exhaled breath
      analysis by electronic nose using LRA is able to discriminate lung cancer
      patients from patients with other lung diseases and from healthy individuals.

PMID- 30221630
TI  - Laparoscopic splenectomy for hereditary spherocytosis. A case series and review
      of the literature.
AB  - : Hereditary spherocytosis (HS) is a common inherited hemolytic anemia caused by
      a defective erythrocyte cellular membrane. Irrespective of type of surgery
      performed, several case reports comparing the two type of procedures, have not
      proven any significant difference between serum bilirubin, serum hemoglobin, red
      blood cells' and platelets' count, in the followup period at 6 and 12 months
      respectively, even if platelet count has maintained high for the first 6 months
      postoperatively, justifying an oral antiplatelet therapy for this time interval.
      In the present work, we present the use of LS as the treatment of choice for HS
      as a case series, with all the characteristics. KEY WORDS: Hereditary
      Spherocytosis, Laparoscopic Splenectomy.

PMID- 30221631
TI  - The use of heterologous bovine pericardium in the surgical treatment of large
      tracheo-oesophageal fistulas and dilaceration of the membranous wall of the
      trachea. Case report.
AB  - : The tracheo-oesophageal fistula is a severe condition endangering the patients'
      live. The main cause of this condition is the prolonged ventilation. The purpose
      of this paper is to present an innovative technique in treating this affection.
      CASE REPORT: We present the case of a 32 years old female patient with multiple
      trauma due to traffic accident. The patient was hospitalized with the diagnosis
      of brain injury, subarachnoid hemorrhage, and fractured femur. After 11 days of
      mechanical ventilation and intubation via endotracheal route, the patient was
      diagnosed with a large (7x3 cm) tracheo-oesophageal fistula with dilaceration of
      the membranous wall of the trachea. A cervical and right thoracic approach was
      performed to repair the tracheo-oesophageal fistula. The reconstruction of the
      membranous wall of the trachea was performed by using heterologous bovine
      pericardium patch, and the of the esophageal defect using single-layer suture
      protected by a heterologous bovine pericardium patch. The postoperative evolution
      was favorable, the patient being discharged 22 days postoperatively and in good
      health after 6 months. To our knowledge this is the first reported case regarding
      the use of two heterologous bovine pericardium in the surgical treatment of large
      tracheo-oesophageal fistula with dilaceration of the membranous wall of the
      trachea to reconstruct the membranous wall of the trachea and to protect the
      esophageal suture. KEY WORDS: Heterologous bovine pericardium, Trachea
      oesophageal fistula.

PMID- 30221632
TI  - Minimally invasive surgical management of impacted maxillary canines.
AB  - AIM: Combined surgical-orthodontic treatment of impacted maxillary canines has
      developed significantly in the last few years, regarding management of both hard
      and soft tissues and forces of traction. The aim of this report is to describe a
      combined surgical-orthodontic approach used to treat an impacted maxillary canine
      and to value the functional and esthetic results after 5 years of followup.
      MATERIALS AND METHODS: A 13-year-old boy had been seen by surgeons in the
      Operative Unit of Orthodontics of Policlinico Tor Vergata in Rome. Radiographic
      images showed intraosseous impaction of teeth 1.3 and 2.3 in a late mixed
      dentition, and the patient was scheduled for the combined surgical-orthodontic
      treatment. RESULTS: After the five-year follow-up, the patient had a good
      occlusal stability. The maxillary canine that had been orthodontically
      repositioned showed an adequate width of attached gingiva, which was well
      keratinized, and the margin of free gingiva that followed the course of the
      cement-enamel junction. Bleeding was absent on probing, the periodontal pocket
      depth was < 4 mm, and there was no radiographically evident bone loss.
      CONCLUSIONS: The combined surgical-orthodontic technique used in this case
      (closed eruption towards the center of the alveolar ridge associated with
      conservative periodontal surgery, the adhesive technique, and controlled
      orthodontic traction) simulates physiological tooth eruption and results in
      proper alignment with good periodontal results. It should be considered as the
      treatment of choice for impacted teeth whose eruption is not precluded by the
      position of the tooth and/or the presence of ankyloses. KEY WORDS: Surgical
      tecnique, Mucoperiosteal flap.

PMID- 30221633
TI  - Comparative analysis of laparoscopic sleeve gastrectomy and Roux-en-Y gastric
      bypass procedures for the treatment of morbid obesity.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) has been considered as the most
      efficient method in bariatric surgery. Indeed, Laparoscopic Sleeve Gastrectomy
      (LSG) which is easier to do, has been increasingly used in the recent years. The
      aim of the present study was to compare short-and mid-term outcomes of RYGB and
      LSG. METHODS: Medical records of 62 patients who underwent either RYGB (GroupR)
      or LSG (GroupL) in our General Surgery Department between 2010 and 2013 were
      retrospectively reviewed. Demographics, comorbidities, preoperative laboratory
      values, length of hospital stay and postoperative complications were recorded.
      During follow-up in the postoperative period, body-mass-index (BMI), excess
      weight loss (EWL), triglyceride levels (TG), and low-density lipoprotein (LDL)
      levels were recorded at the 1st, 3rd, 6th, and 12th months. RESULTS: Mean length
      of hospital stay was significantly higher in GroupR (p = 0.001), which was also
      correlated with BMI. EWL at 1st, 3rd, 6th, and 12th months was significantly
      higher in GroupR. Hair loss was significantly higher in GroupR (p < 0.05). The
      rates of diabetes mellitus and hypertension in the preoperative period and at 6th
      and 12th months did not significantly differ between the groups. Preoperative TG
      and LDL values were significantly higher in GroupR (p < 0.05). CONCLUS ONS: This
      study indicated, that RYGB is statistically more effective than LSG, but LSG has
      clinically almost the same effect as RYGB, and also hospital stay, postoperative
      complications as hair loss are decreased in LSG. KEY WORDS: Laparoscopic Sleeve
      Gastrectomy, Morbid Obesity, Roux-en-Y Gastric Bypass.

PMID- 30221635
TI  - Erratum: The study of service dogs for veterans with Post-Traumatic Stress
      Disorder: a scoping literature review.
AB  - [This corrects the article DOI: 10.1080/20008198.2018.1503523.].

PMID- 30221634
TI  - Strontium Ranelate Combined with Insulin Is as Beneficial as Insulin Alone in
      Treatment of Fracture Healing in Ovariectomized Diabetic Rats.
AB  - BACKGROUND Type 2 diabetes mellitus (T2DM) and estrogen deficiency both
      predispose fracture patients to increased risk of delayed union or nonunion. The
      present study investigated the effects of strontium ranelate (SR) on fracture
      healing in ovariectomized (OVX) diabetic rats. MATERIAL AND METHODS A mid-shaft
      fracture was established in female normal control (CF), diabetic (DF), and OVX
      diabetic (DOF) rats. Treated DOF rats received either insulin alone (DOFI) or
      combined with SR (DOFIS). All rats were euthanized at 2 or 3 weeks after
      fracture. Fracture healing was evaluated using radiological, histological,
      immunohistochemical, and micro-computed tomography analyses. RESULTS At 3 weeks
      after fracture, radiological and histological evaluations demonstrated delayed
      fracture healing in the DF group compared with the CF group, which was
      exacerbated by OVX, as indicated by the significantly lower X-ray score, BMD,
      BV/TV, and Md.Ar/Ps.Cl.Ar, and the markedly decreased OCN and Col I expression in
      the DOF group. All these changes were prevented by insulin alone or combined with
      SR treatment. In comparison with the DOFI group, DOFIS rats displayed markedly
      higher OCN expression at 2 weeks after fracture and Col I expression at 2 and 3
      weeks after fracture. CONCLUSIONS These results demonstrated delayed fracture
      healing with preexisting estrogen deficiency and T2DM. While insulin alone and
      combined with SR were both effective in promoting bone fracture healing in this
      model, their combined treatment showed significant improvement in promoting
      osteogenic marker expression, but not of the radiological appearance, compared
      with insulin alone.

PMID- 30221636
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000489630.].

PMID- 30221637
TI  - [Series: Caries prevention in historical perspective. Education].
AB  - In the Netherlands, since the end of the nineteenth century, information has been
      given to the public about possible ways to prevent dental caries. This happened
      in the dental offices, in health centres where the parents of young children
      received advice, and in schools. From 1968 until the mid-1980s, large-scale
      information campaigns were organised in various municipalities and regions. The
      Ivory Cross, a Dutch society for oral health education, has been providing
      information on oral health and supporting the provision of information for, among
      others, dentists and dental hygienists by offering educational material. The
      understanding of the phenomenon 'information' has changed during the past
      century. By applying new insights, there is an increased chance to prevent caries
      by providing information.

PMID- 30221638
TI  - [A renewed focus on extra-oral manifestations of oral infections].
AB  - Dental focal infections are extraoral manifestations caused by oral pathogens.
      Pathological oral conditions, such as periapical inflammation and periodontitis,
      can cause bacteremia. Dissemination of oral pathogens to nonoral sites can
      subsequently cause infections in extraoral tissues and organs. Cardiovascular
      infections and brain abscesses are the most common of these. The course of such
      infections can be lethal. In order to improve patient care, a closer
      collaboration between dental and medical caregivers is necessary.

PMID- 30221639
TI  - [An (un)conventional autogenous tooth transplantation].
AB  - A 15-year-old boy was referred to an Oral and Maxillofacial Surgery department
      because of a persistent tooth 85 and a malposition of tooth 45. Following
      additional examination, it was concluded that the root formation of tooth 45 was
      already completed. Furthermore, it was horizontally impacted against the inferior
      border of the mandible. The decision was made to extract tooth 85 and to
      autotransplant tooth 45. Post-operatively, tooth 45 was fixed to the orthodontic
      equipment already in place and later treated endodontically. The success rate of
      this kind of autotransplantation of teeth with already closed apices (94%) is
      comparable in the literature to the success rate of autotransplantation of teeth
      with open apices (98%). Autotransplantation should be considered, especially in
      patients who are still growing and for whom dental implants do not (yet) offer a
      solution.

PMID- 30221641
TI  - [Use of information technology to support the oral care of older people living at
      home].
AB  - The use of eHealth has increased rapidly in recent years and is also being
      deployed in several ways in care for older people. Little is still known,
      however, about the use and acceptance of oral care related applications of
      eHealth by older people. By means of interviews, qualitative research was carried
      out on the use of digital devices and the needs of older people living at home
      for oral care related information and instruction via eHealth. Results indicate
      that older people are technically capable of receiving and making use of this
      information via eHealth. Slightly more than half of those questioned were
      interested in receiving this information via an eHealth app. It was considered to
      be useful when reduced mobility hindered visits to the dentist. Furthermore,
      those questioned expressed the opinion that the healthcare they are familiar with
      and the personal contacts should not be replaced by unfamiliar digital
      alternatives.

PMID- 30221640
TI  - [The image of general practitioners compared to that of dentists in the
      Netherlands].
AB  - The image of the professions of family doctor and dentist in the Netherlands was
      investigated by means of a questionnaire distributed online and in four cities.
      In total, 270 questionnaires were analysed. The dentist was seen more as a
      businessman, a solo performer for whom the interests of the patient were less
      highly prioritised, who,was less communicative, more associated with pain, more
      distant, less open to dialogue and could be trusted less than the general
      practitioner. Respondents also felt less safe at the dentist's office than at the
      general practitioner's. On average, respondents rated the general practitioner
      significantly higher than the dentist. Dentists scored significantly lower than
      general practitioners on eleven of the twelve statements. The score of the
      profession dentist was not significantly different from that of general
      practitioner in only one category, professionalism. These results indicate that
      the image of the dental profession is worse than that of the general
      practitioner.

PMID- 30221642
TI  - [A PhD completed. The shortened dental arch and quality of life].
AB  - The question addressed by this doctoral research was whether the concept of the
      shortened dental arch has become an obsolete treatment therapy. To answer this
      question, a systematic review of literature concerning the oral health related
      quality of life of people with a shortened dental arch was carried out, a
      questionnaire among people with and without a shortened dental arch was employed
      to determine the longevity and clinical outcomes of shortened dental arches and
      finally, semi-structured interviews were conducted to assess perceptions and
      attitudes regarding absent molars and prostheses. The conclusion is that in
      certain situations the shortened dental arch concept is still valid. Patients
      with a shortened dental arch experience an oral health related quality of life
      comparable to people with a full dental arch and a shortened dental arch can
      function well for up to 30 years or more. During the joint decision-making
      process about whether to apply the shortened dental arch concept, it is important
      to address the underlying issues involved in having or treating a shortened
      dental arch.

PMID- 30221643
TI  - Fibrin tissue adhesive versus nasal packing in endoscopic nasal surgery: a
      systematic review and meta-analysis.
AB  - BACKGROUND: It has been proposed that fibrin tissue adhesive (FTA) can act as an
      effective alternative to nasal packing in managing the postoperative symptoms of
      endoscopic nasal surgery. METHODOLOGY: MEDLINE, Embase, Cochrane Library, The
      Cumulative Index to Nursing and Allied Health Literature and ClinicalTrials.gov
      were searched for randomised controlled trials comparing FTA with nasal packing
      in endoscopic nasal surgery. The primary outcome of interest was bleeding;
      secondary outcomes included pain, nasal obstruction, infection, adhesions and the
      formation of granulation tissue. All trials underwent a risk of bias assessment,
      and a meta-analysis was performed using a random effects model. RESULTS: 315
      studies were found, of which four were eligible for inclusion (n = 152). Bleeding
      was reported in all, with the meta-analysis favouring the packing group, although
      this was not significant. Nasal obstruction and granulation severity were
      significantly lower in the FTA group, however, no difference was noted for the
      outcomes of pain, infection or adhesions. CONCLUSION: Our results indicate minor
      advantages for using FTA over nasal packing. Unfortunately, the included studies
      show significant heterogeneity and risk of bias. Based on the available evidence,
      clinicians must balance the higher cost of FTA against the limited advantages for
      the patient.

PMID- 30221646
TI  - Correction: A bodipy based hydroxylamine sensor.
AB  - Correction for 'A bodipy based hydroxylamine sensor' by Adam C. Sedgwick et al.,
      Chem. Commun., 2017, 53, 10441-10443.

PMID- 30221644
TI  - Digital enzyme assay using attoliter droplet array.
AB  - Single-molecule digital enzyme assay using micron-sized droplet array is a
      promising analysis method to quantify biomolecules at extremely low
      concentrations. However, multiplex digital enzyme assays are still difficult to
      access because the best buffer conditions can vary largely among enzymes. In
      addition, the best conditions for flurogenic compounds to retain high quantum
      efficiency and to avoid leakage into the oil phase can be also very different. In
      this study, digital enzyme assay was performed using an array of nanometer-sized
      droplets of 200 aL volume, termed 'nanocell'. Due to the small reaction volume,
      nanocell enhanced the accumulation rate of fluorescent products by a factor of
      100 when compared with micron-sized reactors. Nanocell also enabled oil-free
      sealing of reactors: when flushed with an air flow, nanocell displayed water
      droplets under air, allowing enzymes to catalyze the reaction at the same rate as
      in oil-sealed reactors. Dual digital enzyme assay was also demonstrated using
      beta-galactosidase and alkaline phosphatase (ALP) at pH 7.4, which is far from
      the optimum condition for ALP. Even under such a non-optimum condition, ALP
      molecules were successfully detected. Nanocell could largely expand the
      applicability of digital bioassay for enzymes under non-optimum conditions or
      enzymes of low turnover rate. The sealing of the reactor with air would also
      expand the applicability, allowing the use of fluorescent dyes that leak into
      oil.

PMID- 30221645
TI  - Pressure dependence of spin canting in ammonium metal formate antiferromagnets.
AB  - High-pressure single-crystal X-ray diffraction at ambient temperature and high
      pressure SQUID measurements down to 2 K were performed up to ~2.5 GPa on ammonium
      metal formates, [NH4][M(HCOO)3] where M = Mn2+, Fe2+, and Ni2+, in order to
      correlate structural variations to magnetic behaviour. Similar structural
      distortions and phase transitions were observed for all compounds, although the
      transition pressures varied with the size of the metal cation. The
      antiferromagnetic ordering in [NH4][M(HCOO)3] compounds was maintained as a
      function of pressure, and the magnetic ordering transition temperature changed
      within a few kelvins depending on the structural distortion and the metal cation
      involved. These compounds, in particular [NH4][Fe(HCOO)3], showed greatest
      sensitivity to the degree of spin canting upon compression, clearly visible from
      the twenty-fold increase in the low-temperature magnetisation for
      [NH4][Fe(HCOO)3] at 1.4 GPa, and the change from purely antiferromagnetic to
      weakly ferromagnetic ordering in [NH4][Mn(HCOO)3] at 1 GPa. The variation in the
      exchange couplings and spin canting was checked with density-functional
      calculations that reproduce well the increase in canted moment within
      [NH4][Fe(HCOO)3] upon compression, and suggest that the Dzyaloshinskii-Moriya
      (DM) interaction is evolving as a function of pressure. The pressure dependence
      of spin canting is found to be highly dependent on the metal cation, as
      magnetisation magnitudes did not change significantly for when M = Ni2+ or Mn2+.
      These results demonstrate that the overall magnetic behaviour of each phase upon
      compression was not only dependent on the structural distortions but also on the
      electronic configuration of the metal cation.

PMID- 30221647
TI  - A water-processable cellulose-based resist for advanced nanofabrication.
AB  - The ideal nanofabrication technique is one that allows the mass production of
      high resolution submicrometric features in a cost efficient and environmentally
      friendly fashion. A great step towards achieving this goal has been the
      development of nanoimprinting lithography, a procedure with tenths of nanometres
      resolution while being compatible with roll-to-roll manufacturing. However, an
      ecofriendly resist that can be efficiently combined with this process is still
      missing. In this work, we demonstrate the use of hydroxypropyl cellulose (HPC) as
      a biocompatible, biodegradable, and water processable resist for temperature
      assisted nanoimprint lithography (tNIL) by fabricating different photonic
      architectures. The cellulose derivative is easily patterned with submicrometric
      features with aspect ratios greater than 1 using an elastomeric stamp and a hot
      plate. Silicon photonic crystals and metal nanoparticle arrays are fabricated
      combining cellulose with traditional nanofrabrication processes such as
      spincasting, reactive ion etching and metal lift off. Furthermore, advanced
      nanofabrication possibilities are within reach by combining the HPC with
      traditional resists. In particular, poly(methyl methacrylate) and HPC stacks are
      easily produced by liquid phase processing, where one of the two materials can be
      selectively removed by developing in orthogonal solvents. This capability becomes
      even more interesting by including nanoimprinted layers in the stack, leading to
      the encapsulation of arrays of air features in the resist.

PMID- 30221652
TI  - Long-term occupational trajectories and suicide: a 22-year follow-up of the GAZEL
      cohort study.
AB  - Objective Most suicides occur among individuals of working age. Risk is elevated
      in some occupational groups, however relations between long-term occupational
      trajectories and suicide are not well known. We describe career-long occupational
      trajectories and examine their influence on suicide. Methods Data come from
      GAZEL, a French cohort study set among employees of a large national utilities
      company. Occupational grade was obtained from company records from the time of
      hiring (1953-1988). Group-based trajectory models were used to define
      occupational trajectories over a mean time period of 25.0 (standard deviation
      6.5) years. Causes of mortality, coded using the International Classification of
      Diseases, were recorded from 1993-2014 and studied using Cox regression models.
      Results Of the 20 452 participants included in the study, 73 died by suicide
      between 1993-2014. Results suggested an increased risk of suicide [hazard ratio
      (HR) 2.57, 95% confidence interval (CI) 1.08-6.15] among participants with
      persistently low occupational grade compared to those with higher occupational
      grade and career development. After adjustment for all covariates, especially
      psychological factors, this association was reduced and no longer statistically
      significant (HR 2.02, 95% CI 0.82-4.95). Conclusions Persistently low
      occupational grade could be related to an elevated risk of suicide. This
      association partly reflects psychological and health characteristics, which can
      influence occupational trajectories and be reinforced by unfavorable work
      conditions.

PMID- 30221653
TI  - Self-reported or register-based? A comparison of sickness absence data among 8110
      public and private employees in Denmark.
AB  - Objectives The study aim was to examine (i) non-response bias between responders
      and non-responders, and (ii) whether the association between self-reported
      sickness absence (SA) and register-based SA differed by gender, age, sector, or
      physically demanding work. Methods The responses of 8110 participants to a
      question on self-reported SA in past 12 months in the Work Environment and Health
      in Denmark Survey (2014) was linked to 12 months of SA data from the Danish
      Register of Work Absence. We used logistic regression for the non-response
      analysis and Poisson regression to examine associations. Results Responders had
      on average 0.5 days less SA per year than non-responders. Public employees had a
      higher response rate than private employees (approximately five percentage
      points), women had a higher rate than men (approximately nine percentage points),
      and older employees a higher rate than younger employees (approximately nine
      percentage points in ten years). Self-reported SA correlated highly with register
      based SA (Spearman's rank correlation=0.76). In general, responders with few SA
      days (<10) under-reported their SA while responders with many SA days (>30) over
      reported their SA. Women under-reported significantly more than men (average
      difference one day); older employees under-reported significantly more than
      younger employees (difference between age groups 18-29 and 60-64 was 1.7 days).
      Differences between sectors or levels of physically demanding work were non
      significant. Conclusions Self-reported SA data may be influenced by non-response
      bias, and different accuracy in different demographic groups. When available, the
      use of register-based SA data is recommended.

PMID- 30221654
TI  - Evaluation of the effect of various main elements on the PrPSc detection by real
      time quaking-induced conversion assay.
AB  - In order to definitively diagnosis sporadic Creutzfeldt-Jakob disease (sCJD),
      brain tissue is currently required. Therefore, there is a great need for tests
      that can detect sCJD in body fluids or other types of tissues. Different
      variables, including the amount of recombinant celluar prion protein (rPrPC),
      salt, cleaning surfactants and thioflavin T (ThT), in human cerebrospinal fluid
      (CSF) were evaluated. The reagent concentrations of 1X PBS, 170 mM NaCl, 1 mM
      EDTA, 0.01 mM ThT and 0.001% SDS, and the amounts of 10 ug rPrPC and 10 ul CSF
      were considered to be optimal for the real-time quaking-induced conversion (RT
      QuIC) assay. Using these conditions, the RT-QuIC assay for prion protein (PrPSc)
      detection was observed to be sensitive to 10-8 diluted brain homogenates of
      hamsters infected with the 263K scrapie strain. Furthermore, CSF samples from 70
      probable sCJD cases and 48 non-CJD cases were preliminarily screened. A
      substantial proportion of sCJD samples (57.14%) tested positive by RT-QuIC, with
      a short lag phase (<50 h post-reaction) and high peak ThT values (>25,000
      relative fluorescence units). By contrast, only a small number of non-CJD samples
      displayed weakly positive results, and these were detected at a later stage (>50
      h post-reaction) and had much lower ThT values. In conclusion, the RT-QuIC assay
      in CSF samples reported in the present study may provide a useful pre-mortem tool
      for the diagnosis of sCJD, particularly in China where postmortem examination is
      rarely conducted.

PMID- 30221655
TI  - Ursolic acid alleviates inflammation and against diabetes-induced nephropathy
      through TLR4-mediated inflammatory pathway.
AB  - Ursolic acid (UA) is a triterpenoid isolated from Chinese herbal medicine. It is
      extensively distributed in the plant kingdom in at least 63 Chinese herbal
      medicines of 26 families. UA has multiple bioactivities, including anti-viral
      hepatitis, antitumor, anti-oxidation, anti-bacterium and anti-inflammation. The
      aim of this in vitro study was to examine the effects of UA on diabetes-induced
      nephropathy and its possible mechanism. In mice with diabetes-induced
      nephropathy, UA increased the body weight, reduced kidney/body weight index,
      protected kidney cells, alleviated inflammation [tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1beta, IL-6 and IL-18 levels] and kidney cell damage. It
      was also indicated that UA suppressed Toll-like receptor 4 (TLR4), myeloid
      differentiation factor 88 and nuclear factor-kappaB protein expression in mice
      with diabetes-induced nephropathy. The inhibition of TLR4 increased the anti
      inflammation of UA on inflammation in rat with diabetes-induced nephropathy
      through the TLR4 signaling pathway. In conclusion, UA alleviates inflammation and
      inhibits diabetes-induced nephropathy through a TLR4-mediated inflammatory
      pathway. The present findings indicated that UA may be a possible therapeutic
      agent against diabetic nephropathy.

PMID- 30221656
TI  - Protection of insulin-like growth factor 1 on experimental peripheral neuropathy
      in diabetic mice.
AB  - The present study investigated whether insulin-like growth factor-1 (IGF-1)
      exerts a protective effect against neuropathy in diabetic mice and its potential
      underlying mechanisms. Mice were divided into four groups: Db/m (control), db/db
      (diabetes), IGF-1-treated db/db and IGF-1-picropodophyllin (PPP)-treated db/db.
      Behavioral studies were conducted using the hot plate and von Frey methods at 6
      weeks of age prior to treatment. The motor nerve conduction velocity (NCV) of the
      sciatic nerve was measured using a neurophysiological method at 8 weeks of age.
      The alterations in the expression levels of IGF-1 receptor (IGF-1R), c-Jun N
      terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38 and
      effect of IGF-1 on the sciatic nerve morphology were observed by western blotting
      and electron microscopy. Compared with the control group, the diabetes group
      developed hypoalgesia after 12 weeks, and neurological lesions improved following
      an intraperitoneal injection of recombinant (r)IGF-1. The sciatic NCV in the
      diabetes group was significantly lower compared with the control group. The
      sciatic NCV improved following rIGF-1 intervention; however, was impaired
      following administration of the IGF-1 receptor antagonist, PPP. The myelin sheath
      in the sciatic nerve of the diabetes group was significantly more impaired
      compared with the control group. The myelin sheath in the sciatic nerves of the
      rIGF-1-treated group was significantly improved compared with the diabetes group;
      whereas, they were significantly impaired following administration of the IGF-1R
      inhibitor. In addition, the expression of IGF-1R, phosphorylated (p)-JNK and p
      ERK of sciatic nerves in the db/db mice was significantly increased following
      treatment with IGF-1. The expression levels of these proteins were significantly
      lower in the IGF-1-PPP group compared with the IGF-1 group; however, no
      significant difference was observed in the expression levels of p-p38 following
      treatment with IGF-1. The results of the present study demonstrated that IGF-1
      may improve neuropathy in diabetic mice. This IGF-1-induced neurotrophic effect
      may be associated with the increased phosphorylation levels of JNK and ERK, not
      p38; however, it was attenuated by administration of an IGF-1R antagonist.

PMID- 30221657
TI  - Huwe1 is a novel mediator of protection of neural progenitor L2.3 cells against
      oxygen-glucose deprivation injury.
AB  - Hypoxic-ischemic encephalopathy is one of the most notable causes of brain injury
      in newborns. Cerebral ischemia and reperfusion lead to neuronal damage and
      neurological disability. In vitro and in vivo analyses have indicated that E3
      ubiquitin protein ligase (Huwe1) is important for the process of neurogenesis
      during brain development; however, the exact biological function and the
      underlying mechanism of Huwe1 remain controversial. In the present study, neural
      progenitor cells, L2.3, of which we previously generated from rat E14.5 cortex,
      were used to investigate the role of Huwe1 and its effects on the downstream N
      Myc-Delta-like 3-Notch1 signaling pathway during oxygen-glucose deprivation
      (OGD). To evaluate the role of Huwe1 in L2.3 cells, transduction, cell viability,
      lactate dehydrogenase, 5-bromo-2'deoxyurine incorporation, western blotting and
      immunocytochemical assays were performed. The results of the present study
      indicated that Huwe1 rescued L2.3 cells from OGD-induced insults by inhibiting
      proliferation and inducing neuronal differentiation. In addition, Huwe1 was
      suggested to mediate the survival of L2.3 cells by inhibiting the activation of
      the N-Myc-Notch1 signaling pathway. Of note, the effects of Huwe1 on Notch1
      signaling were completely abolished by knockdown of N-Myc, indicating that Huwe1
      may require N-Myc to suppress the activation of the Notch1 signaling in L2.3
      cells. The determination of the neuroprotective function of the Huwe1-N-Myc
      Notch1 axis may provide insight into novel potential therapeutic targets for the
      treatment of ischemic stroke.

PMID- 30221658
TI  - Silencing of perilipin by short hairpin RNA inhibits proliferation and induces
      apoptosis in liposarcoma cells.
AB  - Previous studies have identified that perilipin-1 (PLIN1) is a highly specific
      marker for liposarcoma. However, its functions have yet to be fully elucidated.
      The aim of the present study was to investigate the potential role of PLIN1 in
      the proliferation, migration and apoptosis of liposarcoma cells. Short hairpin
      RNA was designed to inhibit PLIN1 levels. Cell proliferation was monitored by
      Cell Counting Kit-8 assay and cell migration determined by wound healing assay.
      Flow cytometry was performed to assess the cell cycle distributions and apoptosis
      in liposarcoma cells. The results demonstrated that the expression of PLIN1 was
      significantly upregulated in liposarcoma tumor tissues compared with normal
      adipose tissues. Silencing of PLIN1 by short hairpin RNA significantly inhibited
      proliferation and migration and induced G1 phase cell cycle arrest and apoptosis
      in liposarcoma cell lines. It was identified that PLIN1 serves a crucial role in
      the pathogenesis and progression of liposarcoma and may be a potential
      therapeutic target for its clinical management.

PMID- 30221659
TI  - Analysis of virulence diversity of 73 Helicobacter pylori strains isolated in
      Guizhou province, China.
AB  - The present study aimed to investigate the virulence diversity of Helicobacter
      pylori (H. pylori) in major ethnic groups residing in Guizhou province, China,
      and its association with clinical outcomes. Gastric mucosal biopsies were
      collected from the pylorus of patients with gastrointestinal disorders. H. pylori
      was identified by colonial morphology, Gram staining, a urease test and H. pylori
      specific 16S rRNA gene fragment PCR amplification. DNA was extracted from pure
      culture and used for virulence gene analysis. The cytotoxin associated gene A
      (cagA), vacuolating cytotoxin A (vacA) and induced by contact with epithelium
      gene A (iceA) genes were analyzed by polymerase chain reaction analysis. The cagA
      gene was further analyzed through sequencing of the C-terminal region containing
      EPIYA motifs, and phylogenetic analysis of the cagA C-terminal variable region
      was performed using MEGA 6.0 software. In the present study, 73 H. pylori strains
      were isolated from clinical samples. cagA genotypes were detected in all strains,
      namely cagA-AB, -ABC, -ABD and -BD genotypes were found in five (6.85%), three
      (4.11%), 63 (86.30%) and two (2.74%) isolates, respectively. Phylogenetic
      analysis showed that there was a clustering association between the cagA-AB and
      cagA-ABC genotypes, and between the cagA-ABD and cagA-BD genotypes. In terms of
      the frequency of the four EPIYA or EPIYA-like motifs, the most predominant was
      EPIYA (92.92%), followed by EPIYT (3.77%), ESIYA (2.83%) and ESIYT (0.47%). The
      predominant vacA genotype was s1c/m2 (65.75%), and the predominant iceA genotype
      was iceA1 (79.45%). There were no associations between the H. pylori cagA, vacA
      or iceA genotypes and clinical outcomes. No significant difference was found in
      the distribution of these genotypes according to the age, ethnicity or location
      of residence of patients. In conclusion, H. pylori isolated from patients in
      Guizhou region, China, showed a unique genotype, which was mainly East Asia-type
      cagA (ABD), vacA s1c/m2 genotype or iceA1-postiive. These results provide
      important information on the distribution of H. pylori virulence genotypes in
      Guizhou province, China.

PMID- 30221660
TI  - [Corrigendum] Correlation between the expression of IL-18 and deep venous
      thrombosis.
AB  - In the above paper, the authors realize that an error inadvertently appeared in
      the funding section on p. 895. Where "This study was supported by the National
      Natural Science Foundation of China Science Fund Project (grant no. 30960389 and
      8176010097)" was written, the application number 8176010097 was featured
      incorrectly: This should have been written as grant no. 81760030. Therefore, this
      sentence in the funding section should have read as follows: "This study was
      supported by the National Natural Science Foundation of China Science Fund
      Project (grant nos. 30960389 and 81760030)". The authors regret this error was
      not noticed prior to the publication, and apologize to their funding body and to
      the readership of the Journal for any inconvenience caused. [the original article
      was published in International Journal of Molecular Medicine 42:883-896, 2018;
      DOI: 10.3892/ijmm.2018.3682].

PMID- 30221661
TI  - SFRP5 serves a beneficial role in arterial aging by inhibiting the proliferation,
      migration and inflammation of smooth muscle cells.
AB  - Secreted frizzled-related protein 5 (SFRP5) is one of the anti-inflammatory
      adipokines secreted from white adipose tissue. However, little is known about the
      effect of SFRP5 on the cardiovascular system. The aim of the present study was to
      determine the effect of SFRP5 on smooth muscle cell (SMC) proliferation,
      migration and inflammation. The plasma levels of SFRP5 were evaluated in a cohort
      based elderly population using ELISA, and the expression of SFRP5 in Sprague
      Dawley rat aortas was detected using immunohistochemistry. SMC proliferation and
      migration were evaluated in vitro using 5-ethynyl-2'-deoxyuridine cell
      proliferation and wound-healing assays, respectively, while reactive oxygen
      species (ROS) production and cell signaling were assessed using a 2',7'
      dichlorodihydrofluorescein diacetate assay and immunoblotting, respectively. The
      results revealed that plasma levels of SFRP5 were positively correlated with age
      in the elderly Chinese cohort. Similarly, aorta SFRP5 expression was
      significantly higher in 15-month-old rats compared with 6-month-old rats. In
      vitro, SFRP5 significantly inhibited rat aortic SMC proliferation and migration
      that were induced by platelet-derived growth factor (PDGF)-BB, as well as
      inhibiting ROS generation. Compared with the effect of PDGF-BB on SMCs, SFRP5 at
      100 and 200 ng/ml significantly decreased SMC proliferation by 31.5 and 34.8%,
      respectively (P<0.05). SFRP5 at 100 and 200 ng/ml also inhibited the migration of
      SMCs by 24.9 and 28.4%, respectively, when compared with the effects of PDGF-BB.
      SFRP5 attenuated the PDGF-BB-induced expression of beta-catenin and proliferating
      cell nuclear antigen, while p38 phosphorylation was significantly attenuated.
      Together, the present results suggested that SFRP5 may inhibit SMC proliferation,
      migration and inflammation by suppressing the Wnt/beta-catenin and p38/mitogen
      activated protein kinase signaling pathways.

PMID- 30221662
TI  - O-GlcNAc-modified SNAP29 inhibits autophagy-mediated degradation via the
      disturbed SNAP29-STX17-VAMP8 complex and exacerbates myocardial injury in type I
      diabetic rats.
AB  - The O-linked beta-N-acetylglucosamine (O-GlcNAc) modification and autophagy are
      associated with diabetic myocardial injury, however, the molecular mechanisms
      between the two processes remain to be fully elucidated. The purpose of the
      present study was to elucidate the molecular regulation of autophagy by O-GlcNAc
      modified synaptosomal-associated protein 29 (SNAP29) in diabetic myocardial
      injury. A rat model of type I diabetes was established via intraperitoneal
      injection of streptozotocin (STZ; 55 mg/kg). Significant increases in the O
      GlcNAc modification and accumulation of the autophagy markers microtubule
      associated protein 1 light chain 3alpha II/I and P62, which suggest that
      autophagic flux is inhibited, were observed in rats 8 weeks following STZ
      induction. Subsequently, the selective O-GlcNAcase inhibitor, thiamet G,
      increased the level of O-GlcNAc modification, which further disrupted autophagic
      flux; deteriorated cardiac diastolic function, as indicated by an increased left
      ventricular filling peak velocity/atrial contraction flow peak velocity ratio
      shown by echocardiography; and exacerbated myocardial abnormalities, as
      characterized by cardiomyocyte disorganization and fat and interstitial fibrosis
      accumulation. By contrast, 6-diazo-5-oxo-L-norleucine, an inhibitor of
      glucosamine fructose-6-phosphate aminotransferase isomerizing 1, acted as an O
      GlcNAc antagonist and reduced the level of O-GlcNAc modification, which
      maintained autophagic flux and improved cardiac diastolic function. In vitro,
      high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes
      (NRCMs). Consistent with the myocardium of diabetic rats, it was also shown in
      the NRCMs that O-GlcNAc modification of SNAP29 negatively regulated autophagic
      flux. The application of the short hairpin RNA interference lysosome-associated
      membrane protein (LAMP2) and the autophagy inhibitor 3-methyladenine demonstrated
      that high glucose inhibited autophagy-mediated degradation rather than affected
      the initial stage of autophagy. Finally, co-immunoprecipitation was used to
      determine the role of the O-GlcNAc-modified substrate protein SNAP29, which acted
      as an SNAP29-syntaxin-17 (STX17)-vesicle-associated membrane protein 8 (VAMP8)
      complex during disease progression. The present study is the first, to the best
      of our knowledge, to demonstrate that SNAP29 is an O-GlcNAc substrate and that an
      increase in O-GlcNAc-modified SNAP29 inhibits SNAP29-STX17-VAMP8 complex
      formation, thereby inhibiting the degradation of autophagy and exacerbating
      myocardial injury in type I diabetic rats.

PMID- 30221663
TI  - Post-transplant lymphoproliferative disorder in hematopoietic stem cell
      transplant patients: A single center retrospective study between 2005 and 2012.
AB  - Post-transplant lymphoproliferative disorder (PTLD), despite its rarity, is an
      important mortality/morbidity event in transplant patients. The purpose of the
      present study was to retrospectively examine the clinical and pathologic
      characteristics, and outcomes of PTLD at the Portuguese Oncology Institute of
      Porto. A retrospective review of patient information was performed for patients
      that developed PTLD following allogeneic hematopoietic stem cell transplant
      (aHSCT) and were diagnosed between 2005 and 2012. The present study included a
      total of 15 patients, 8 females (53.3%) and 7 males (46.7%), with different
      clinicopathological characteristics. The most frequent clinical condition
      inducing aHSCT was acute lymphocytic leukemia (40.0%). Conditioning regimens
      consisted primarily in busulfan and cyclophosphamide, with anti-thymocyte
      globulin, and myeloablation was the preferential treatment. Epstein-Barr virus
      (EBV) was present in all patients with a median time of diagnosis following
      transplant of 75 days (range, 25-485 days) and a median viral load of 4.75 log10
      copies/ml (range, 3.30-6.26 log10 copies/ml). PTLD diagnosis was mainly assessed
      by clinical findings, and histological confirmation was available for 5 patients:
      3 monomorphic, 1 polymorphic and 1 with early lesions of PTLD. To the best of our
      knowledge, this is the first study to describe PTLD cases in HSCT patients in
      Portugal. The data reinforces the importance of performing EBV monitoring in high
      risk patients, particularly those receiving a transplant from mismatch/unrelated
      donors, and those with myeloablative conditioning regimen including antithymocyte
      globulin. The results also suggested that EBV viral load may be significant for
      the prediction of PTLD development.

PMID- 30221664
TI  - Effect of emodin on T cell subsets in NOD mice with NaI-induced experimental
      autoimmune thyroiditis.
AB  - Chronic lymphocytic thyroiditis (CLT), also known as Hashimoto's thyroiditis, is
      an autoimmune disease in which the thyroid gland is gradually destroyed. To date,
      only a limited number of agents can effectively suppress thyroiditis development
      in CLT patients. The aim of the current study was to investigate the protective
      effect of emodin on experimental autoimmune thyroiditis (EAT) in mice, which is
      considered an excellent model for CLT. NaI was used to induce the EAT model in
      non-obese diabetic (NOD) mice. An ELISA method was employed to detect the TgAb
      level (thyroid inflammation) in the serum of the EAT mice. The T cell subsets in
      peripheral blood and spleen were detected by flow cytometry. The
      histopathological study revealed that the thyroid inflammatory cell infiltration
      was significantly reduced by emodin compared with the model group. In addition,
      ELISA assays indicated that the NaI-induced serum TgAb upregulation was
      dramatically revered by emodin. Moreover, the level of serum IFN-gamma and the
      cell populations of CD3+CD4+IL-4+, CD3+CD4+ IFN-gamma+, CD3+CD8+IL-4+, CD3+CD8+
      IFN-gamma+ T cells in peripheral blood monocytes and splenic lymphocytes were
      significantly increased by NaI in the model group compared with in the normal
      group. Nevertheless, this type of increase was markedly attenuated by emodin. To
      conclude, the EAT model was successfully established by treating NOD mice with
      NaI. Emodin indicated an inhibitory effect on the autoimmune response that was
      significantly different in EAT compared with control mice. Furthermore, the anti
      inflammatory action of emodin on EAT mice may be mediated via the inhibition of
      the secretion of IFN-gamma and the cell numbers of CD3+CD4+IL-4+, CD3+CD4+ IFN
      gamma+, CD3+CD8+IL-4+ and CD3+CD8+ IFN-gamma+ T cells in the peripheral blood
      monocytes and splenic lymphocytes. Therefore, the data may offer valuable insight
      on the efficacy of treatment of CLT with emodin.

PMID- 30221665
TI  - Protective effects of taurine against inflammation, apoptosis, and oxidative
      stress in brain injury.
AB  - The protective effect of taurine against inflammation, apoptosis and oxidative
      stress in traumatic brain injury was investigated in the present study. Taurine
      is a non-proteogenic and essential amino acid in animals. It plays a critical
      nutritional role in brain cell growth, differentiation, and development. Taurine
      is involved in regeneration and neuroprotection in the injured nervous system,
      and is an effective antioxidant against lead-, cadmium-, and exercise-induced
      oxidative stress. Astrocytes and neuron cells were co-cultured and cells were
      treated with different concentrations of taurine (100, 200 and 300 mg/l) for 72
      h, and the levels of reactive oxygen species, malondialdehyde, reduced
      glutathione, glutathione peroxidase, superoxide dismutase, catalase,
      acetylcholinesterase, tumor necrosis factor-alpha, interleukin-6, caspase-3, p53,
      B-cell lymphoma 2 and Bcl-2-associated X protein were determined. These
      inflammatory, apoptotic, and oxidative stress markers were substantially
      increased in injured cells, and returned to normal levels following taurine
      supplementation. Thus, taurine supplementation may be effective against oxidative
      stress, apoptosis, and inflammation in injured brain cells.

PMID- 30221667
TI  - Bafilomycin A1 alleviates depression-like symptoms in chronic unpredictable mild
      stress rats.
AB  - Major depression is a multifactorial disease. Emerging evidence has suggested
      that autophagy is involved in the pathological process of depressive disorders.
      Bafilomycin A1 (Baf A1), is an inhibitor of vacuolar H+-ATPase that is frequently
      used at high concentrations to block late-phase autophagy. However, whether Baf
      A1 has antidepressant effects remains to be elucidated. The current study aimed
      to evaluate the antidepressant effects of Baf A1 in rats with chronic
      unpredictable mild stress (CUMS) and its potential mechanism. The CUMS animal
      model was established. The sucrose preference test, open-field test (OFT) and
      forced swim test (FST) were applied to evaluate the depressive behavior. Synaptic
      plasticity-associated proteins synaptophysin and postsynaptic density protein 95
      were measured by western blotting and immunofluorescence. Apoptosis- and
      autophagy-associated proteins in addition to pro-inflammatory cytokines,
      including interleukin-1beta and tumor necrosis factor-alpha, were detected by
      western blotting, reverse transcription-quantitative polymerase chain reaction or
      ELISA. A 4-week treatment period with Baf A1 markedly ameliorated CUMS-induced
      behavioral abnormalities, including increasing sucrose intake, improving
      locomotor activity in the OFT, and decreasing immobility time in the FST. In
      addition, treatment with Baf A1 restored the dysregulation of synaptic plasticity
      and inhibited neuroinflammation in rats exposed to CUMS. Furthermore, Baf A1
      decreased the levels of apoptosis- and autophagy-associated proteins induced by
      CUMS. The present study demonstrated that Bafilomycin A1 resulted in
      antidepressant effects in rats, which may be mediated by the reversal of
      apoptosis, autophagy and neuroinflammation in the hippocampus.

PMID- 30221666
TI  - Downregulation of FOXK2 is associated with poor prognosis in patients with
      gastric cancer.
AB  - Forkhead box (FOX)K2 (FOXK2) is a member of the FOX transcription factor family.
      It has been suggested previously that FOXK2 is required to suppress tumor growth;
      however, the exact role of FOXK2 in gastric cancer remains to be elucidated. In
      the present study, the association between FOXK2 expression and the
      clinicopathological characteristics of patients with gastric cancer was
      investigated. The prognostic value of FOXK2 expression and the significance of
      clinicopathological parameters in the overall survival (OS) and progression-free
      survival of patients were also determined by survival analysis. To investigate
      the functional roles of FOXK2, it was downregulated in BGC-823 cells using small
      interfering (si)RNA, and upregulated using a FOXK2 plasmid. Colony formation,
      Cell Counting Kit-8 and cell proliferation analyses were conducted to examine the
      proliferation of gastric cancer cells. Transwell and wound-healing assays were
      performed to investigate the effect of FOXK2 expression on gastric cancer cell
      migration and invasion. The clinical data demonstrated that FOXK2 expression was
      reduced in high-grade gastric cancer tissues, and a low level of FOXK2 expression
      indicated a poor prognosis. The data obtained from the Human Protein Atlas
      revealed that patients with gastric cancer and a high level of FOXK2 expression
      had a longer OS time. The results of colony formation assays, Transwell and wound
      healing assays demonstrated that FOXK2 repressed the proliferation, invasion and
      migration of gastric cancer cells, respectively. The findings indicated that
      FOXK2 may serve as a promising therapeutic target in gastric cancer. Taken
      together, the findings of the present study demonstrated that FOXK2 functions as
      a tumor suppressor in gastric cancer; the loss of FOXK2 may induce the growth and
      invasion of gastric cancer cells.

PMID- 30221669
TI  - Long noncoding RNA LINC00978 promotes cell proliferation and invasion in non
      small cell lung cancer by inhibiting miR-6754-5p.
AB  - Long noncoding RNA LINC00978 has been reported to regulate the progression of
      several human types of cancer, including gastric and breast cancer. However,
      knowledge on LINC00978 in non-small cell lung cancer (NSCLC) is limited. In the
      present study, it was demonstrated that LINC00978 expression was significantly
      upregulated in NSCLC tissues compared with the adjacent normal tissues.
      Furthermore, LINC00978 expression was positively correlated with the tumor, node
      and metastasis stage, and lymph node metastasis in NSCLC patients. Additionally,
      LINC00978 knockdown significantly inhibited the proliferation, migration and
      invasion of NSCLC cells while promoting cell apoptosis. In terms of the
      underlying mechanism, it was demonstrated that LINC00978 served as a competing
      endogenous RNA sponge for microRNA (miR)-6754-5p, which was downregulated in
      NSCLC tissues. The present study demonstrated that there was a negative
      correlation between LINC00978 and miR-6754-5p expression levels in NSCLC tissues.
      Additionally, it was demonstrated that inhibition of miR-6754-5p reversed the
      effects of LINC00978 knockdown on NSCLC cell proliferation, migration, invasion
      and apoptosis. In conclusion, results of the present study demonstrated that
      LINC00978 exerts an oncogenic role in NSCLC by inhibiting miR-6754-5p expression.

PMID- 30221668
TI  - Methylation status of KLF4 and HS3ST2 genes as predictors of endometrial cancer
      and hyperplastic endometrial lesions.
AB  - Endometrial carcinoma is one of the most common tumours in developed countries.
      In addition to the active role of genetic factors, epigenetic changes also have
      an important effect. The present study analysed the methylation status of kruppel
      like factor 4 (KLF4) and heparan sulfate-glucosamine 3-sulfotransferase 2
      (HS3ST2) genes in three endometrial tissue types for carcinoma prediction. The
      sample comprised 91 women with histologically-confirmed endometrial carcinoma
      (64.16+/-9.64 years old), 36 women with hyperplasia (53.39+/-9.64 years old) and
      45 with no signs or symptoms of malignancy (48.53+/-11.11 years old). The CpG
      dinucleotide methylation levels were examined by quantitative pyrosequencing, and
      the discrimination accuracy of the model was calculated using the Random Forest
      classification algorithm of the area under the ROC curve (AUC). The mean values
      of KLF4 and HS3ST2 methylation indices were 23.83+/-11.39 and 8.52+/-2.57 in the
      control samples; 30.40+/-8.52 and 33.76+/-20.66 in hyperplasia and 34.72+/-10.79
      and 34.49+/-18.39 in the cancerous tissues. Multinomial logistic regression
      indicated that the HS3ST2 CpG1 methylation status is a predictor of hyperplasia
      (P<0.05) and that the KLF4 CpG2 dinucleotide can predict carcinoma formation
      (P<0.001). The AUC value of 0.95 indicates high discrimination accuracy of the
      CpG nucleotides methylation status model between the controls and the two other
      diagnoses. The results of the present study establish the likelihood that
      aberrations in KLF4 and HS3ST2 gene methylation levels are important in the
      development of endometrial hyperplasia and carcinoma, with hyperplasia an
      intermediate step between healthy and tumour tissues.

PMID- 30221670
TI  - Tizanidine exerts anti-nociceptive effects in spared nerve injury model of
      neuropathic pain through inhibition of TLR4/NF-kappaB pathway.
AB  - Recently, alpha2-adrenoceptors (alpha2-AR) agonists have been shown to have anti
      nociceptive effects and thus may become a promising therapeutic strategy for
      neuropathic pain. tizanidine is a highly selective alpha2-AR agonist, but the
      effect mechanism of tizanidine in neuropathic pain remains largely unknown. The
      present study investigated whether tizanidine has anti-nociceptive effects in
      spared nerve injury (SNI) model of neuropathic pain in rats, as well as explored
      the underlying molecular mechanism. We found that the rats in SNI group showed
      significantly higher mechanical and thermal hyperalgesia, accompanied with
      increased production of proinflammatory cytokines including interleukin-1beta (IL
      1beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha), as well as the
      activation of Toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-kappaB)
      signaling. PDTC, an inhibitor of TLR4/NF-kappaB signaling, could significantly
      attenuate the SNI-induced mechanical and thermal hyperalgesia and the production
      of proinflammatory cytokines. Moreover, treatment with tizanidine also attenuated
      the SNI-induced mechanical and thermal hyperalgesia, suppressed production of the
      proinflammatory cytokines, and inhibited the activation of TLR4/NF-kappaB
      pathway, which could be reversed by pretreatment with BRL44408, a selective
      alpha2-AR antagonist. Taken these findings together, we demonstrated that
      tizanidine has anti-nociceptive effects on neuropathic pain via inhibiting the
      production of proinflammatory cytokines through suppressing the activation of
      TLR4/NF-kappaB p65 signaling pathway.

PMID- 30221672
TI  - In vitro free radical scavenging capacity of dimethylglycine sodium salt and its
      protective ability against oleic acid hydroperoxide-induced oxidative damage in
      IPEC-J2 cells.
AB  - The aim of the present study was to evaluate the in vitro free radical scavenging
      capacity of dimethylglycine sodium (DMG-Na) and its protective ability against
      oleic acid hydroperoxide (OAHPx)-induced oxidative damage in IPEC-J2 cells.
      Initially, the free radical scavenging activities of water-soluble pigments (DMG
      Na, betalain, capsanthin and cyanidin-3-rutinoside) were measured and compared
      with those of Trolox. Subsequently, freshly collected swine blood was mixed with
      heparin and centrifuged to obtain erythrocytes. In order to induce the free
      radical chain oxidation in erythrocytes, the aqueous peroxyl radicals were
      generated by thermal decomposition of 2,2'-azobis(2-amidinopropane)
      dihydrochloride (AAPH) in oxygen. A 2% suspension of porcine erythrocytes in PBS
      buffer were pre-incubated for 30 min at 37C with DMG-Na (32 uM), followed by
      incubation with or without AAPH (75 mM) for 5 h with gentle shaking.
      Additionally, IPEC-J2 cells were randomly assigned to four groups (n=6 per
      group): Cells treated with phosphate buffered saline (PBS); cells treated with
      DMG-Na (32 uM); cells treated with oleic acid hydroperoxides (OAHPx, 20 uM; TO
      group); cells treated with DMG-Na (32 uM) followed by OAHPx (20 uM; DTO group).
      The cells were cultured in Dulbecco's modified Eagle's medium, Ham's F-12
      mixture, 1.5 mM HEPES, 5% (v/v) fetal bovine serum, 1% (v/v) insulin-transferrin
      selenium mixture, 1% (v/v) penicillin-streptomycin mixture and 2.5 ug/ml
      fungizone (37C, 5% CO2). The results showed that DMG-Na exerted the strongest
      free radical scavenging capacity at 0.32 M from 0.08-0.64 M, and that it could
      prevent AAPH-induced porcine erythrocyte hemolysis by increasing its antioxidant
      capacity (P<0.05). The results also demonstrated that antioxidant capacity and
      antioxidant-associated gene expression increased in the DTO group relative to the
      TO group (P<0.05), indicating that DMG-Na prevented the OAHPx-induced oxidative
      damage in IPEC-J2 cells by improving the antioxidant capacity and antioxidant
      associated gene expression.

PMID- 30221673
TI  - Identification of three aquaporin subgroups from Blomia tropicalis by
      transcriptomics.
AB  - Aquaporins (AQPs), or water channel proteins, are highly conserved across
      species. These transmembrane proteins promote water and solute transport across
      cell membranes. No AQP-related proteins have been identified in mites to date.
      The present study used transcriptomics (RNA-sequencing) to identify potential
      AQPs in the mite species Blomia tropicalis. Molecular cloning techniques were
      then used to obtain the full-length gene sequences encoding these AQP family
      members, and bioinformatics analyses were used to categorize them based on
      similarity to AQPs in other species. This approach led to the identification of 5
      putative AQP-coding sequences, known as BlotAQP1-5 (GenBank accession numbers:
      KX655540, KX655541, KX655542, KX655543 and KX655544, respectively), which were
      indexed into all three subgroups, i.e., AQPs, aquaglyceroporins and superAQPs. To
      the best of our knowledge, these represent the first known AQPs in any mite
      species. Further studies are required to investigate their functional roles in
      water transport and their potential as drug targets.

PMID- 30221671
TI  - Comprehensive analysis of multi Ewing sarcoma microarray datasets identifies
      several prognosis biomarkers.
AB  - Ewing sarcoma (ES) is a common primary malignancy in children and adolescents.
      Progression of treatment methods hasn't contributed a lot to the imrovement of
      prognosis. To identify potential prognostic biomarkers, a meta-analysis pipeline
      of multi-gene expression datasets for ES from the Gene Expression Omnibus (GEO)
      was performed. Three datasets were screened and differential expression genes
      (DEGs) in ES samples compared with normal tissues were identified through limma
      package and subjected to network analysis. As a result, 1,470 DEGs were obtained
      which were mainly involved in biological processes associated with immune
      response and transcription regulation. Network analysis obtained 22 core genes
      with high network degree and fold change. Kaplan-Meier analysis based on ES
      datasets from The Cancer Genome Atlas identified five genes, including glycogen
      phosphorylase, muscle-associated, myocyte-specific enhancer factor 2C, tripartite
      motif containing 63, budding uninhibited by benzimidazoses1 and Ras GTPase
      activating protein 1, whose altered expression profiles are significantly
      associated with survival. Changes of their expression values were further
      confirmed through RT-qPCR in ES cell and normal cell lines. Those genes may be
      considered as potential prognostic biomarkers of ES and should be helpful for its
      early diagnosis and treatment.

PMID- 30221674
TI  - Prognostic value and potential function of splicing events in prostate
      adenocarcinoma.
AB  - Prostate adenocarcinoma (PRAD) is one of the most common types of malignancy in
      males and at present, effective prognostic indicators are limited. The
      development of PRAD has been associated with abnormalities in alternative
      splicing (AS), a requisite biological process of gene expression in eukaryotic
      cells; however, the prognostic value of AS products and splicing events remains
      to be elucidated. In the present study, the data of splicing events and the
      clinical information of PRAD patients were obtained from The Cancer Genome Atlas
      (TCGA)SpliceSeq and TCGA databases, respectively. A prognostic index (PI) was
      generated from disease-free survival-associated splicing events (DFS-SEs), which
      were identified by univariate/multivariate Cox regression analysis. A total of
      6,909 DFS-SEs were identified in PRAD. The corresponding genes for the DFS-SEs
      were significantly enriched in mitochondria and their associated pathways
      according to Gene Ontology annotation and in the pathways of fatty acid
      metabolism, oxidative phosphorylation and Huntington's disease according to a
      Kyoto Encyclopedia of Genes and Genomes pathway analysis. The PI for mutually
      exclusive exons had the greatest ability to predict the probability of five-year
      disease-free survival of patients with PRAD, with an area under the time
      dependent receiver-operating characteristic curve of 0.7606. Patients with PRAD,
      when divided into a 'low' and a 'high' group based on their median PI for exon
      skip values, exhibited a marked difference in disease-free survival (low vs.
      high, 3,588.45+/-250.51 vs. 1,531.08+/-136.50 days; P=7.43x10-9). A correlation
      network between DFS-SEs of splicing factors and non-splicing factors was
      constructed to determine the potential mechanisms in PRAD, which included the
      potential regulatory interaction between the splicing event of splicing factor
      RNA binding motif protein 5-alternate terminator (AT)-64957 and the splicing
      event of non-splicing factor heterochromatin protein 1 binding protein 3-AT-939.
      In conclusion, the PIs derived from DFS-SEs are valuable prognostic factors for
      patients with PRAD, and the function of splicing events in PRAD deserves further
      exploration.

PMID- 30221675
TI  - Y-box binding protein-1 and STAT3 independently regulate ATP-binding cassette
      transporters in the chemoresistance of gastric cancer cells.
AB  - Y-box binding protein-1 (YB-1) facilitates cancer chemoresistance through the
      upregulation of ATP-binding cassette (ABC) transporters associated with multidrug
      resistance, which is one of the primary obstacles in cancer treatment. Since
      aberrant Janus kinase (JAK)/signal transducer and activator of transcription
      (STAT) signaling is also implicated in chemoresistance in numerous human
      malignancies, the interaction between YB-1 and JAK/STAT signaling was explored
      underlying the chemoresistance of NUGC3 gastric cancer cells. It was demonstrated
      that YB-1 translocated into the nuclei of NUGC3 cells exposed to doxorubicin
      hydrochloride, suggesting its important role in chemoresistance. Consistently,
      knockdown of YB-1 significantly decreased the chemoresistance of cells to
      doxorubicin hydrochloride and epirubicin hydrochloride, as evidenced by a
      decrease in cell viability. Notably, JAK inhibitor AG490 treatment further
      decreased the cell viability caused by YB-1 inhibition and doxorubicin
      hydrochloride. It was also observed that YB-1 transcriptionally regulated the
      ABCC3 transporter, whereas STAT3 modulated ABCC2 transporter levels. These
      findings suggest that YB-1 and STAT3 act together to facilitate chemoresistance
      via modulating the expression of different ABC transporters in NUGC3 cells.
      Notably, siYB-1 did not exhibit any significant effect on STAT3 expression.
      Similarly, siSTAT3 failed to alter YB-1 expression, suggesting that the two may
      not regulate each other in a mutual manner. However, double knockdown of YB-1 and
      STAT3 led to a synergistic inhibition of cell invasion in NUGC3 cells.
      Nonetheless, the combined treatment of YB-1 antagonists with STAT3 inhibitors may
      serve as an effective therapy in gastric cancer.

PMID- 30221676
TI  - Lipocalin 2 inversely regulates TRAIL sensitivity through p38 MAPK-mediated DR5
      regulation in colorectal cancer.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis through death
      receptors (DRs)4 and/or 5 expressed on the cell surface. Multiple clinical trials
      are underway to evaluate the antitumor activity of recombinant human TRAIL and
      agonistic antibodies to DR4 or DR5. However, their therapeutic potential is
      limited by the high frequency of cancer resistance. In this study, we provide
      evidence demonstrating the role of lipocalin 2 (LCN2) in the TRAIL-mediated
      apoptosis of human colorectal cancer (CRC). By analyzing the mRNA expression data
      of 71 CRC tissues from patients, we found that DR5 was preferentially expressed
      in CRC tissues with a low LCN2 expression level compared to tissues with a high
      LCN2 expression level. Moreover, we analyzed the association between DR5 and LCN2
      expression and this analysis revealed that DR5 expression in CRC tended to be
      inversely associated with LCN2 expression. By contrast, no association was found
      between the DR4 and LCN2 expression levels. The expression patterns of LCN2 in
      human CRC cell lines also exhibited an inverse association with DR5 expression.
      The knockdown of LCN2 by siRNA in the TRAIL-resistant CRC cells expressing high
      levels of LCN2 led to a significant increase in TRAIL-induced apoptosis through
      the upregulation of DR5 protein and mRNA expression. The mechanism through which
      LCN2 silencing sensitized the CRC cells to TRAIL was dependent on the extrinsic
      pathway of apoptosis. In addition, we identified that the knockdown of LCN2
      enhanced the sensitivity of the cells to TRAIL through the p38 MAPK/CHOP
      dependent upregulation of DR5. Taken together, the findings of this study suggest
      that LCN2 is responsible for TRAIL sensitivity and LCN2 may thus prove to be a
      promising target protein in DR-targeted CRC therapy.

PMID- 30221677
TI  - Establishment of a non-coding RNAomics screening platform for the regulation of
      KRAS in pancreatic cancer by RNA sequencing.
AB  - KRAS oncogene point mutations occur in >95% of patients with pancreatic cancer.
      The KRAS protein can activate various downstream effector molecules that affect
      proliferation and differentiation. MS2 binding sites (MS2bs) are RNAs of 19 bp in
      length that can bind MS2 coat proteins with their specific stem-loop structure.
      The MS2 binding site sequence of the 19-nucleotide stem-loop is
      ACATGAGGATCACCCATGT. We constructed an expression vector that expresses the KRAS
      non-coding region coupled with 12 copies of MS2bs in series and established a
      high-throughput library for collecting microRNA (miRNA or miR)- and long non
      coding RNA (lncRNA)-omics that regulate KRAS. To the best of our knowledge, this
      is the first study to combine RNA-protein interactions with RNA sequencing to
      obtain KRAS-associated non-coding RNAs. As a result, we identified several miRNA
      precursors that belong to the let-7 and miR-34, -30 and -143 families, as well as
      relevant lncRNAs and their families (MALAT1, MEG3_2 and TUG1_1-4). Our databank
      of non-coding RNAs (mainly miRNAs and lncRNAs) that regulate KRAS is expected to
      greatly enhance our understanding of KRAS regulation-associated tumorigenesis and
      may aid in the development of gene therapies for pancreatic cancer.

PMID- 30221678
TI  - Suppressive effect of an analog of the antimicrobial peptide of LL-37 on colon
      cancer cells via exosome-encapsulated miRNAs.
AB  - Antimicrobial peptides (AMPs) are multifunctional factors with an important role
      in the innate immune system. Our previous studies revealed that the human
      cathelicidin LL-37 and its analog, FF/CAP18, limit the proliferation of colon
      cancer cell lines. In the present study, the exosomes released by HCT116 cells
      treated with FF/CAP18 were analyzed. After the treatment, exosomes were isolated
      from the culture supernatant by ultrafiltration and using the miRCURYTM Exosome
      Isolation Kit. Membrane vesicles 40-100-nm expressing CD63 and CD81 were
      identified before and after FF/CAP18 treatment. Exosome concentration in the
      culture supernatant was increased after treatment with FF/CAP18. Exosomes formed
      in HCT116 cells treated with FF/CAP18 induced growth suppression of the cells in
      a dose-dependent manner. By contrast, the exosomes formed in non-treated HCT116
      cells did not affect cell viability. Microarray analysis of miRNA expression
      indicated that FF/CAP18 treatment induced increases in the expression of three
      miRNAs (miR-584-5p, miR-1202 and miR-3162-5p) in both HCT116 cells and exosomes.
      These results suggest that FF/CAP18 treatment increases exosome formation, and
      that exosome-encapsulated miRNAs suppress HCT116 cell proliferation. Exosomal
      miRNAs are considered to be involved in the dissemination of cell signals to
      control local cellular microenvironments. The present findings suggest that
      FF/CAP18 regulates cancer growth by modulating cell-to-cell communication. AMPs
      localize in the cytoplasm of cancer cells and enhance the expression of growth
      suppressing miRNAs. These miRNAs are also transported to other cancer cells via
      exosomes. Therefore, transportation of these miRNAs has the potential to suppress
      cancer growth. AMPs exert their effects directly by targeting cancer cells and
      indirectly via exosomes.

PMID- 30221680
TI  - Hyperosmotic stress stimulates autophagy via the NFAT5/mTOR pathway in
      cardiomyocytes.
AB  - Hyperosmotic stress may be initiated during a diverse range pathological
      circumstances, which in turn results in tissue damage. In this process, the
      activation of survival signaling, which has the capacity to restore cell
      homeostasis, determines cell fate. Autophagy is responsible for cell survival and
      is activated by various pathological stimuli. However, its interplay with
      hyperosmotic stress and its effect on terminally differentiated cardiac myocytes
      is unknown. Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive
      transcription factor, mediates the expression of cell survival associated-genes
      under hyperosmotic conditions. The present study investigated whether NFAT5
      signaling is required in hyperosmotic stress-induced autophagy. It was
      demonstrated that the presence of a hyperosmotic stress induced an increase in
      NFAT5 expression, which in turn triggered autophagy through autophagy-related
      protein 5 (Atg5) activation. By contrast, NFAT5 silencing inhibited DNA damage
      response 1 protein expression, which then initiated the activation of mammalian
      target of rapamycin signaling. Therefore, the balance between NFAT5-induced
      apoptosis and autophagy may serve a critical role in the determination of the
      fate of cardiomyocytes under hyperosmotic stress. These data suggest that
      autophagy activation is a beneficial adaptive response to attenuate hyperosmotic
      stress-induced cell death. Therefore, increasing autophagy through activation of
      NFAT5 may provide a novel cardioprotective strategy against hyperosmotic stress
      induced damage.

PMID- 30221679
TI  - Anti-obesity and fatty liver-preventing activities of Lonicera caerulea in high
      fat diet-fed mice.
AB  - Blue honeysuckle (BH, Lonicera caerulea) is used as a traditional medicine in
      Russia, Japan and China, but is not commonly considered as an edible berry in
      Europe, USA or Korea. BH has been revealed to decrease serum cholesterol and
      triacylglycerol (triglyceride or TG) levels through the activation of AMP
      activated protein kinase (AMPK), thus it is expected to be a health functional
      food and pharmaceutical agent for the prevention of non-alcoholic liver damage,
      in addition to effects as a suppressor of hyperlipidemia and as an anti-obesity
      agent. In the present study, the pharmacological activity of BH extract (BHe) was
      observed in high-fat diet (HFD)-fed mice. Significant increases in fat pad
      weight, body weight, fat accumulation (body and abdominal fat density, and
      thickness of the periovarian and abdominal wall) and serum biochemical levels
      (aspartate transaminase, alanine aminotransferase, alkaline phosphatase, lactate
      dehydrogenase, gamma-glutamyltransferase, total cholesterol, low-density
      lipoprotein and TG, with the exception of high-density lipoprotein) were observed
      in HFD-fed mice. In addition, increases in adipocyte hypertrophy, the area of
      steatohepatitis and hepatocyte hypertrophy were observed, whereas decreased
      zymogen content was identified upon histopathological observation. Increased
      deterioration of the endogenous antioxidant defense system (liver catalase,
      glutathione and superoxide dismutase) and hepatic lipid peroxidation was
      observed. In addition, there were decreases in hepatic glucokinase activity,
      AMPKalpha1 and AMPKalpha2 mRNA expression, adipose tissue uncoupling protein 2
      expression, and adiponectin mRNA expression, increases in phosphoenolpyruvate
      carboxykinase and glucose-6-phosphatase activity, hepatic acetyl-CoA carboxylase
      1 mRNA expression, and the expression of leptin, CCAAT/enhancer-binding protein
      (C/EBP) alpha, C/EBPbeta and sterol-regulatory-element-binding protein 1c mRNA in
      the periovarian tissue. Furthermore, non-alcoholic fatty liver disease (NAFLD)
      and obesity were significantly inhibited by the continuous administration of BHe
      for 84 days. These results revealed that BHe may be a promising novel drug or
      functional food candidate for the treatment of obesity and NAFLD.

PMID- 30221682
TI  - Regulation of the MAPK signaling pathway by miR-421-5p in rats under light
      pollution.
AB  - The present study aimed to explore the difference in the expression profiles of
      ovarian microRNA sequences in rats in a light pollution environment and rats in a
      normal light environment. Rats in the control group were exposed to 12-h
      light/dark cycles, while rats in the model group were continuously exposed to 24
      h light. The ovaries were extracted from the two groups of rats, and Illumina
      HiSeq 2500 high-throughput sequencing technology was used to detect the
      differences in microRNA (miRNA) expression among the two groups. Fluorescence
      quantitative reverse transcription-polymerase chain reaction was used to verify
      the differential expression of miRNA. The present study was designed to
      experimentally validate the interaction between miR-421-5p and mitogen-activated
      protein kinase (MAPK) 7 by using the dual-luciferase reporter system, and to
      explore the expression of proteins in the MAPK signaling pathway with a
      lentiviral vector-mediated small hairpin RNA interference against microRNA-421
      5p. The expression of 45 miRNAs was significantly different. In total, 13 miRNAs
      were upregulated, of which 5 miRNA sequences were known and 8 were predicted.
      Furthermore, 32 miRNAs were downregulated, of which 11 miRNA sequences were known
      and 21 were predicted. The results of the luciferase reporter assay confirmed the
      targeting association between miR-421-5p and MAPK7. The expression levels of MAPK
      and genes in its downstream signaling pathways, including c-Fos, CREB and c-Myc,
      were downregulated when miR-421-5p was overexpressed and upregulated when miR-421
      5p was silenced. The differential expression of miRNAs may serve an important
      role in the development of the ovary in a light pollution environment. miR-421-5p
      may regulate ovarian growth and development by targeting the MAPK signaling
      pathway in light polluted rat ovaries.

PMID- 30221681
TI  - Silencing of NOD2 protects against diabetic cardiomyopathy in a murine diabetes
      model.
AB  - The aim of the present study was to investigate the role of the nucleotide
      binding oligomerization domain (NOD) 2 in high glucose (HG)-induced myocardial
      apoptosis and fibrosis in mice. Mouse models of diabetes were induced by
      streptozotocin (STZ). NOD2 expression was knocked down by injection of lentivirus
      mediated short-hairpin RNA. Alternatively, small interfering RNA-NOD2 was
      transfected into cardiomyocytes and cardiac fibroblasts (CFs). A hemodynamic
      assay was used to assess the cardiac function in the mouse model. Hematoxylin and
      eosin, Masson and terminal deoxynucleotidyl transferase dUTP nick end labeling
      staining was performed to observe pathological changes and injury of myocardial
      tissue. The expression levels of NOD2, collagen I and III, and transforming
      growth factor-beta (TGF-beta) and apoptotic proteins were quantified by reverse
      transcription-quantitative polymerase chain reaction and western blotting. NOD2
      silencing ameliorated diabetes-induced myocardial apoptosis and fibrosis in mice.
      NOD2, collagen I, collagen III, TGF-beta and pro-apoptotic proteins were
      upregulated in the diabetic cardiomyopathy (DCM) model group, but interference of
      NOD2 suppressed these alterations in protein expression levels. NOD2 is
      upregulated in HG-induced primary cardiomyocytes and CFs. Suppression of NOD2
      attenuated HG-induced cardiomyocyte apoptosis and proliferation of CFs. Overall,
      NOD2 silencing alleviated myocardial apoptosis and fibrosis in diabetic mice. The
      results of the present study demonstrated an understanding of the role of NOD2 in
      diabetes-induced cardiomyopathy, which provides a novel target and therapies for
      the prevention and treatment of DCM.

PMID- 30221684
TI  - Effect of deubiquitinase USP8 on hypoxia/reoxygenation-induced inflammation by
      deubiquitination of TAK1 in renal tubular epithelial cells.
AB  - Intermittent hypoxia/reoxygenation (IHR), characterized by repeated episodes of
      hypoxia interspersed with periods of reoxygenation, has been found to induce pro
      inflammatory cytokine production and is increasingly recognized as a major
      pathophysiological factor in various disease processes with distinct cell and
      molecular responses. The present study is the first, to the best of our
      knowledge, to investigate the effects of ubiquitin-specific peptidase 8 (USP8) on
      IHR-induced inflammation in renal tubular epithelial cells and examine the
      underlying mechanism. Following transfection of plasmids, HK-2 and TCMK-1 cells
      were incubated for eight cycles of IHR treatment including 3 h of hypoxic
      incubation followed by 3 h of normoxic culture. It was demonstrated that the
      expression of USP8 was decreased in IHR conditions but not in normoxic or
      continuous hypoxic conditions. In addition, IHR-induced inflammation was
      suppressed in USP8-overexpressinh renal tubular epithelial cells, and the
      silencing of USP8 markedly aggravated inflammation. Furthermore, it was found
      that the overexpression of USP8 inhibited the IHR-induced activation of nuclear
      factor-kappaB and it was demonstrated that USP8 interacted with transforming
      growth factor-beta-activated kinase-1 (TAK1) and deubiquitinated the K63-linked
      ubiquitination of TAK1. Taken together, the results demonstrated the role of USP8
      in IHR-induced inflammation and suggested USP8 as a potential and specific
      therapeutic target for IHR-related diseases.

PMID- 30221683
TI  - Aspirin promotes apoptosis and inhibits proliferation by blocking G0/G1 into S
      phase in rheumatoid arthritis fibroblast-like synoviocytes via downregulation of
      JAK/STAT3 and NF-kappaB signaling pathway.
AB  - Rheumatoid arthritis (RA) is a commonly occurring autoimmune disease. Its
      defining pathological characteristic is the excessive proliferation of fibroblast
      like synoviocytes (FLS), which is similar to tumor cells and results in a range
      of clinical problems. As a commonly used antipyretic, analgesic and anti
      inflammatory drug, aspirin is the first-line treatment for RA. However, its
      mechanism of action has not been well explained. The goal is to investigate the
      biological effects of aspirin on primary RA-FLS and its underlying mechanisms. In
      this experiment we treated cells with various concentrations of aspirin (0, DMSO,
      1, 2, 5, 10 mM). Cell proliferation activity was detected with CCK-8 assays.
      Apoptosis and cell cycle distribution were detected via flow cytometry. Apoptosis
      and cell cycle-associated proteins (Bcl-2, Bax, PRAP1, Cyclin D1, P21), as well
      as the key proteins and their phosphorylation levels of the NF-kappaB and
      JAK/STAT3 signaling pathways, were detected via western blot analysis.
      Bioinformatics prediction revealed that aspirin was closely associated with cell
      proliferation and apoptosis, including the p53 and NF-kappaB signaling pathways.
      By stimulating with aspirin, cell viability decreased, while the proportion of
      apoptotic cells increased, and the number of cells arrested in the G0/G1 phase
      increased in a dose-dependent manner. The expression of Bax increased with
      aspirin stimulation, while the levels of Bcl-2, PRAP1, Cyclin D1 and P21
      decreased; p-STAT3, p-P65 and p-50 levels also decreased while STAT3, P65, P50, p
      P105 and P105 remained unchanged. From our data, it can be concluded that aspirin
      is able to promote apoptosis and inhibit the proliferation of RA-FLS through
      blocking the JAK/STAT3 and NF-kappaB signaling pathways.

PMID- 30221595
TI  - Effect of Aspirin on All-Cause Mortality in the Healthy Elderly.
AB  - BACKGROUND: In the primary analysis of the Aspirin in Reducing Events in the
      Elderly (ASPREE) trial, now published in the Journal, we report that the daily
      use of aspirin did not provide a benefit with regard to the primary end point of
      disability-free survival among older adults. A numerically higher rate of the
      secondary end point of death from any cause was observed with aspirin than with
      placebo. METHODS: From 2010 through 2014, we enrolled community-dwelling persons
      in Australia and the United States who were 70 years of age or older (or >=65
      years of age among blacks and Hispanics in the United States) and did not have
      cardiovascular disease, dementia, or disability. Participants were randomly
      assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were
      classified according to the underlying cause by adjudicators who were unaware of
      trial-group assignments. Hazard ratios were calculated to compare mortality
      between the aspirin group and the placebo group, and post hoc exploratory
      analyses of specific causes of death were performed. RESULTS: Of the 19,114
      persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to
      receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of
      follow-up. The risk of death from any cause was 12.7 events per 1000 person-years
      in the aspirin group and 11.1 events per 1000 person-years in the placebo group
      (hazard ratio, 1.14; 95% confidence interval [CI], 1.01 to 1.29). Cancer was the
      major contributor to the higher mortality in the aspirin group, accounting for
      1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of
      the participants in the aspirin group and in 2.3% of those in the placebo group
      (hazard ratio, 1.31; 95% CI, 1.10 to 1.56). CONCLUSIONS: Higher all-cause
      mortality was observed among apparently healthy older adults who received daily
      aspirin than among those who received placebo and was attributed primarily to
      cancer-related death. In the context of previous studies, this result was
      unexpected and should be interpreted with caution. (Funded by the National
      Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).

PMID- 30221685
TI  - miR-183 inhibits autophagy and apoptosis in gastric cancer cells by targeting
      ultraviolet radiation resistance-associated gene.
AB  - Ultraviolet radiation resistance-associated gene (UVRAG) regulates autophagy by
      promoting the formation and maturation of autophagosomes. The aim of the present
      study was to investigate the effects of UVRAG and UVRAG-targeting miRNA on the
      regulation of autophagy and apoptosis in gastric cancer (GC). TargetScan was used
      to predict that miR-183 targets the 3'-untranslated region (UTR) of UVRAG, while
      the interaction between miR-183 and the 3'-UTR of UVRAG was assessed using a dual
      luciferase reporter assay. Autophagy was induced in the GC cell line MKN28 by
      serum starvation. miR-NC mimics, miR-183 mimics, miR-NC inhibitors and miR-183
      inhibitors were transfected into MKN28 cells, followed by assessment of the UVRAG
      expression, cell viability and cell apoptosis by western blotting, reverse
      transcription-quantitative polymerase chain reaction, Cell Counting Kit-8 and
      flow cytometry, respectively. It was demonstrated that autophagy resulted in miR
      183 downregulation and overexpression of UVRAG mRNA and protein in MKN28 cells.
      Transfection with miR-183 mimic or inhibitor affected the expression of miR-183
      and, consequently, UVRAG. miR-183 overexpression reversed the starvation-induced
      inhibition of cell proliferation, while inhibition of miR-183 reduced the
      proliferation of GC cells. miR-183 overexpression reversed starvation-induced
      apoptosis, while miR-183 inhibition promoted starvation-induced apoptosis in GC
      cells. Finally, miR-183 overexpression attenuated starvation-induced autophagy
      (LC-3), apoptosis (Bax/Bcl-2) and UVRAG expression, while miR-183 inhibition
      exerted the opposite effects. In conclusion, the results of the present study
      indicated that miR-183 inhibits starvation-induced autophagy and apoptosis by
      targeting UVRAG in human GC cells.

PMID- 30221686
TI  - MicroRNA-552 promotes hepatocellular carcinoma progression by downregulating
      WIF1.
AB  - MicroRNAs (miRNAs/miRs) are involved in the metastasis of hepatocellular
      carcinoma (HCC). In the present study, it was demonstrated that miR-552 was
      upregulated in HCC tissues. High miR-552 expression was associated with malignant
      clinicopathological features and decreased survival rates. The in vitro results
      indicated that miR-552 overexpression promoted migration, invasion and epithelial
      mesenchymal transition in Hep3B cells. However, the knockdown of miR-552
      inhibited its oncogenic roles in Huh-7 cells. Additionally, Wnt inhibitory factor
      1 (WIF1) was demonstrated to be a direct target of miR-552 in Hep3B and Huh-7
      cells. Additional experiments identified that miR-552 promotes beta-catenin
      expression by increasing the phosphorylation of GSK3beta at Ser9. In conclusion,
      the results suggested that miR-552 may promote HCC progression by blocking WIF1
      mediated GSK3beta dephosphorylation. miR-552 may be a biomarker for predicting
      the outcomes of patients with HCC.

PMID- 30221687
TI  - [Study on the Element Composition of Ancient Fossils and Meteorites].
AB  - The ancient fossils are formed by the ancient animals and plants after a long
      geological period and geological processes. They have witnessed the history of
      the earth and recorded the information of the evolution of the earth's ecological
      environment; Meteorites traveling in the solar system for a long time with the
      abrasion of nuclear reactions and atmosphere of the universe, have formed a
      unique shape and texture. They recorded the original information about the
      formation and evolution of out space. The analysis of the ancient fossils
      composition is the scientific basis for the study of the origin and evolution of
      the earth; the meteorites as rock sample from outer space are gifts from nature.
      They are extremely valuable and rare; the analysis of the composition of
      meteorites can provide a better foundation for the development of the foreign
      planet exploration and the development of the celestial chemistry. In this paper,
      the method of sample dissolution was selected and optimized. The final choice of
      nitric acid, hydrofluoric acid and perchloric acid as the mixed reagent, a
      microwave digestion method was used in treatment of ancient fossil samples; The
      aqua regia, nitric acid, hydrofluoric acid and perchloric acid as the mixed
      reagent, both microwave digestion method and wet digestion method were used in
      treatment of meteorite samples. Inductively coupled plasma atomic emission
      spectrometry (ICP-AES) was used to determine three different ancient fossil
      samples and three meteorite samples. And the content of same elements was
      compared. Analysis results show that the ancient fossils and meteorites contain
      Pb, Hg, Ge, Fe, Ni, Cu, Co, Mn and other heavy metal elements as well as part of
      the rare earth element. The standard addition recovery of the method was between
      98.2%~106%, and the relative standard deviation was less than 2.12%. The method
      had high sensitivity, accuracy and precision.

PMID- 30221688
TI  - Expression and mutations of BRCA in breast cancer and ovarian cancer: Evidence
      from bioinformatics analyses.
AB  - Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) are the most well-known genes
      linked to breast cancer and ovarian cancer, which are crucial in DNA repair and
      transcriptional regulation. The present study aimed to elucidate the expression
      profiles, mutations and interaction networks of BRCA1 and BRCA2, which may
      provide insights to reveal the mechanisms of BRCA genes ultimately leading to
      breast or ovarian tumorigenesis. Bioinformatics analyses were performed in the
      present study. The mRNA levels of BRCA1 and BRCA2 were evaluated using FIREHOSE
      analysis, SAGE Genie tools and Oncomine analysis. cBioPortal analysis, and
      Catalogue Of Somatic Mutations In Cancer analysis were used to examine the BRCA1
      and BRCA2 mutations. Kaplan-Meier Plotter analysis was performed to identify the
      prognostic roles of BRCA1 and BRCA2 in breast cancer and ovarian cancer. The
      results of the present study showed that the mRNA expression levels of BRCA1 and
      BRCA2 were elevated in breast cancer and ovarian cancer tissues, compared with
      their matched normal tissues. Second, several common mutations of BRCA1 and BRCA2
      genes were identified in breast cancer and ovarian cancer. Finally, neurofibromin
      1, synaptonemal complex protein 2 and tumor protein 53 were predicted to be
      involved in the interaction network of BRCA1 and BRCA2 in breast cancer and
      ovarian cancer. Taken together, these results provide a significant insight into
      certain mutations and proteins involved in the interaction network of BRCA1 and
      BRCA2, which may have common roles in breast cancer and ovarian cancer. However,
      the complex mechanism underlying these observations remains to be fully
      elucidated, and further investigations are required in the future.

PMID- 30221692
TI  - Cantharidin inhibits melanoma cell proliferation via the miR-21-mediated PTEN
      pathway.
AB  - Cantharidin (CTD) is an active component isolated from the blister beetle that
      has been demonstrated to exert antitumor effects on multiple types of cancer. The
      current study aimed to investigate whether the potential inhibitory effects of
      CTD exist in human melanoma cells and to assess the underlying antitumor
      mechanisms of CTD. Using the Cell Counting Kit-8 assay, it was demonstrated that
      CTD treatment reduced A375 cell proliferation significantly in a dose-dependent
      manner. The colony formation assay demonstrated that CTD treatment could decrease
      the number of A375 cell colonies. Using subcutaneous xenograft tumor models, it
      was also demonstrated that CTD retarded solid tumor growth significantly.
      Furthermore, CTD treatment could induce A375 cell apoptosis, as detected by
      Annexin V-fluorescein isothiocyanate/propidium iodide staining and western blot
      analysis. Notably, CTD treatment reduced microRNA (miR)-21 expression and
      enhanced phosphatase and tensin homolog (PTEN) protein expression levels in A375
      cells. Furthermore, overexpressing miR-21 in A375 cells with the miR-21 agomir
      blocked the antitumor effect of CTD both in vitro and in vivo. Finally, it was
      demonstrated that the inhibitory effects of CTD on A375 cells may be regulated by
      attenuating miR-21-mediated PTEN suppression. Based on these observations, it was
      suggested that CTD be used as a novel anti-proliferation agent of human melanoma
      via targeting the miR-21-PTEN signaling pathway.

PMID- 30221691
TI  - Photothermal therapy with AuNRs and EGFRmAb-AuNRs inhibits subcutaneous
      transplantable hypopharyngeal tumors in nude mice.
AB  - The present study aimed to investigate the effects of photothermal therapy with
      gold nanorods (AuNRs) or epidermal growth factor receptor monoclonal antibody
      conjugated AuNRs (EGFRmAb-AuNRs) on hypopharyngeal carcinoma (HC) in nude mice.
      In addition, the associated signaling pathways were explored. Briefly, a
      subcutaneous transplantable hypopharyngeal tumor model was established in nude
      mice injected with FaDu human HC cells. A total of 70 nude mice were randomly
      divided into seven groups, each of which received a different treatment. Mice
      were treated with AuNRs, locally or through intravenous injection, whereas
      EGFRmAb or EGFRmAb-AuNRs were only administered locally. Near infrared
      spectroscopy (NIR) was also applied for plasmonic photothermal therapy (PPTT).
      The growth curve and the inhibitory rate for tumor growth were used to evaluate
      the effects of each treatment. Flow cytometry and the terminal-deoxynucleotidyl
      transferase dUTP nick end labeling assay were adopted to detect apoptosis of
      cells in the transplanted tumors. Reverse transcription-quantitative polymerase
      chain reaction and western blotting were used to determine the mRNA and protein
      expression levels of target genes, respectively. Local treatment with AuNRs + NIR
      or EGFRmAb significantly inhibited tumor growth, and EGFRmAb conjugation further
      increased the inhibitory effects. Furthermore, there was a significant increase
      in apoptosis of tumor cells in the AuNRs + NIR, EGFRmAb and EGFRmAb-AuNRs + NIR
      groups; treatment with EGFRmAb-AuNRs + NIR induced the highest apoptotic effect.
      Mechanistic studies indicated that EGFRmAb-AuNRs + NIR may inhibit tumors through
      the AKT serine/threonine kinase (Akt) and DNA damage signaling pathways. In the
      AKT pathway, the mRNA and protein expression levels of phosphatase and tensin
      homolog were increased, whereas the expression levels of Akt and glycogen
      synthase kinase 3beta were decreased. In the DNA damage signaling pathway, the
      mRNA and protein expression levels of ATR serine/threonine kinase, checkpoint
      kinase 1 and p53 were enhanced, whereas phosphorylated-p53 protein expression was
      reduced. The present findings indicated that AuNRs + NIR inhibited HC tumor
      growth, and conjugating EGFRmAb to AuNRs further enhanced the inhibitory effects.
      EGFRmAb conjugation may increase the antitumor effects of AuNRs-induced PPTT by
      downregulating the phosphatidylinositol-3-kinase/Akt pathway and upregulating the
      DNA damage pathway. These findings may provide novel insights into tumor
      targeting PPTT in vivo.

PMID- 30221689
TI  - DPY30 is required for the enhanced proliferation, motility and epithelial
      mesenchymal transition of epithelial ovarian cancer cells.
AB  - Epithelial ovarian cancer (EOC) is one of the most lethal gynecological
      malignancies and is known to be associated with the accumulation of various
      genetic and epigenetic alterations. As a member of the human histone-lysine N
      methyltransferase SETD1A (SET1)/histone-lysine N-methyltransferase 2A (MLL)
      complexes that are required for full SET1/MLL methyltransferase activity, protein
      dpy-30 homolog (DPY30) catalyzes histone H3K4 methylation, and its dysfunction
      has been associated with the occurrence of cancer. Therefore, the present study
      investigated the role of DPY30 in EOC and the potential association between DPY30
      expression and the clinicopathological characteristics of EOC. The expression of
      DPY30 was examined in EOC tissues and cell lines to identify any correlations
      between the clinicopathological characteristics of EOC and DPY30 expression, and
      to determine the effects of DPY30 on EOC cell proliferation, migration and
      invasion. DPY30 was highly expressed in EOC tissues and cell lines, and high
      DPY30 expression was significantly associated with notable clinicopathological
      variables in EOC patients, including International Federation of Gynecology and
      Obstetrics stage, pathological grade and lymph node metastasis. Functional
      studies on EOC cell lines demonstrated that DPY30 significantly promoted cell
      proliferation, migration, and invasion, accelerated cell cycle progression, and
      promoted epithelial-mesenchymal transition. Chromatin immunoprecipitation assay
      results revealed that DPY30 regulates histone H3K4 modification via interaction
      with the vimentin gene promoter, suggesting that DPY30 promotes the transcription
      of vimentin. Finally, high expression of DPY30 was significantly associated with
      reduced survival in patients with EOC. The results indicated that DPY30 may act
      as an oncogene in EOC and thus represents a potential therapeutic target and
      prognostic marker in EOC.

PMID- 30221690
TI  - Astragalus polysaccharide combined with 10-hydroxycamptothecin inhibits
      metastasis in non-small cell lung carcinoma cell lines via the MAP4K3/mTOR
      signaling pathway.
AB  - Non-small cell lung carcinoma (NSCLC) is a life-threatening malignancy. The level
      of the cell growth regulator mitogen-activated protein kinase kinase kinase
      kinase 3 (MAP4K3) has been shown to be correlated with a high risk of NSCLC
      recurrence and poor recurrence-free survival rate. The present study examined the
      effects of Astragalus polysaccharide (APS) and 10-hydroxycamptothecin (HCPT),
      which are associated with marked suppression and dephosphorylation of the
      MAP4K3/mammalian target of rapamycin (mTOR) signaling pathway, in the H1299 NSCLC
      cell line. APS and HCPT decreased H1299 cell viability, induced apoptosis and
      altered the cell cycle stages, as evaluated using an 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay and flow cytometric analysis. Furthermore,
      APS increased the expression of apoptosis-associated genes B-cell lymphoma 2 (Bcl
      2) and Bcl-2-associated X protein (BAX), of proteases cysteine-aspartic acid
      protease (caspase)-3 and -9, and of cytochrome c. HCPT promoted autophagy in
      H1299 cells, with concomitant suppression of the expression of MAP4K3 and
      downregulation of mTOR signaling. Notably, combination treatment with the two
      agents reduced the migration and invasion of H1299 cells compared with the single
      treatments. It was also demonstrated that the overexpression of MAP4K3 promoted
      the migration and invasion of H1299 cells, and that the kinase activity was
      essential to this. These findings suggested that MAP4K3 may be an attractive
      target for the treatment of NSCLC.

PMID- 30221693
TI  - High expression of Copine 1 promotes cell growth and metastasis in human lung
      adenocarcinoma.
AB  - Despite advances in diagnosis and treatment, the survival of non-small cell lung
      cancer (NSCLC) patients is poor. Further understanding of the disease mechanism
      and treatment strategies is required. Copines are a family of calcium-dependent
      phospholipid-binding proteins that are evolutionally conserved in various
      eukaryotic organisms and protists. Copine 1, encoded by CPNE1, is a soluble
      membrane-binding protein, which includes two tandem C2 domains at the N-terminus
      and an A domain at the C-terminus. A previous study reported that Copine 1 binds
      with various intracellular proteins via its A domain and C  omain. However, the
      role of CPNE1 in lung cancer remains unclear. In the presented study, CPNE1
      expression level was demonstrated to be positively associated with the stage
      (P=0.002) and significantly associated with lymph node status (P=0.011) and
      distant metastasis (P=0.042). Furthermore, the function of CPNE1 in regulation of
      cell growth, migration and invasion was investigated, and it was demonstrated
      that knockdown of CPNE1 inhibits the cell cycle in NSCLC cells. Collectively,
      these data suggest that CPNE1 is an oncogene in NSCLC and serves an important
      role in tumorigenesis of NSCLC progression.

PMID- 30221694
TI  - Role of the Rho/ROCK signaling pathway in the protective effects of fasudil
      against acute lung injury in septic rats.
AB  - Fasudil, which is primarily prescribed to treat cerebral vasospasm, may also
      inhibit systemic inflammation and prevent sepsis-induced acute lung injury (ALI)
      in rats, although the mechanisms remain elusive. The purpose of the present study
      was to investigate the role of the rhodopsin (Rho)/Rho-associated protein kinase
      (ROCK) signaling pathway in the protective effects of fasudil on ALI in septic
      rats. A total of 60 Wistar rats were pretreated with fasudil (30 mg/kg) through
      intraperitoneal injections 1 h prior to cecal ligation and puncture.
      Administration of fasudil led to reductions in polymorphonuclear neutrophil
      counts, and the protein concentrations of tumor necrosis factor-alpha,
      interleukin (IL)-1beta and IL-6 in the bronchoalveolar lavage fluid of rats with
      sepsis-induced ALI. The results demonstrated that fasudil decreased sepsis
      induced bacteremia. In addition, fasudil effectively reduced the Evans blue
      content, wet/dry lung weight ratio, lung injury score, and expression levels of
      malondialdehyde and myeloperoxidase. However, the superoxide dismutase activity
      in the lung tissue of the rats was increased. Activated caspase-3 activity in
      lung tissue was reduced to 29% by fasudil. Furthermore, the expression of Rho and
      ROCK1 was significantly downregulated, and the phosphorylation of myosin
      phosphatase-targeting subunit 1 in lung tissues was markedly decreased, whereas
      the protein expression levels of zonula occludens 1 were increased in fasudil
      treated rats (P<0.05). In the in vitro experiments, vascular endothelial growth
      factor, intracellular adhesion molecule 1 and vascular cell adhesion molecule 1
      secreted from human pulmonary microvascular endothelial cells treated with
      lipopolysaccharide (LPS) were attenuated by fasudil. Fasudil also reduced the
      fluorescence intensity of filamentous actin induced by LPS. Taken together, the
      results of the present study demonstrated that fasudil was able to improve
      endothelial permeability and inhibit inflammation, oxidative stress and cellular
      apoptosis in order to alleviate ALI in septic rats through inhibition of the
      Rho/ROCK signaling pathway.

PMID- 30221695
TI  - CXCL12 induces migration of oligodendrocyte precursor cells through the CXCR4
      activated MEK/ERK and PI3K/AKT pathways.
AB  - Demyelination is a nervous system disease in which the myelin sheaths of neurons
      are damaged due to inflammatory reactions, inherited abnormalities or trauma.
      This damage impairs the conduction of signals in the affected nerves, which in
      turn causes deficiencies in sensation, movement and cognition. Oligodendrocyte
      precursor cells (OPCs) are able to induce remyelination. However, the
      remyelination is suboptimal due to the limited migration of OPCs. In the present
      study, neonatal OPCs were isolated from rats for the investigation of the role of
      C-X-C motif chemokine ligand 12 (CXCL12), an important chemokine, in mediating
      the migration ability of OPCs. The present results demonstrated that CXCL12
      stimulation markedly promoted the migration of OPCs and activated the dual
      specificity mitogen-activated protein kinase kinase 1 (MEK)/extracellular signal
      regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/RAC-alpha
      serine/threonine-protein kinase (AKT) pathways. Knockdown of C-X-C motif
      chemokine receptor 4 (CXCR4; a receptor of CXCL12) reversed the CXCL12-induced
      migration of OPCs and blocked the MEK/ERK and PI3K/AKT pathways. In addition,
      specific inhibitors of the MEK/ERK and PI3K/AKT pathways significantly reduced
      the migration of OPCs. Based on these findings, it was concluded that CXCL12 may
      induce the migration of OPCs through the CXCR4-activated MEK/ERK and PI3K/AKT
      pathways. The results of the present study support the manipulation of CXCL12
      mediated OPC migration to improve remyelination.

PMID- 30221696
TI  - LIMD2 targeted by miR-34a promotes the proliferation and invasion of non-small
      cell lung cancer cells.
AB  - A previous study indicated that LIM domain containing 2 (LIMD2) is an oncogene in
      a variety of human cancers, including breast, bladder and thyroid cancers, and
      melanoma; however, the role of LIMD2 in non-small cell lung cancer (NSCLC)
      remains largely unknown. In the present study, by reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) analysis, it was demonstrated
      that LIMD2 was significantly upregulated in NSCLC tissues compared with adjacent
      normal tissues. Consistently, LIMD2 was also upregulated in NSCLC cell lines.
      Furthermore, the present study reported that knockdown of LIMD2 significantly
      inhibited the proliferation and invasion of H1299 and A549 cells by Cell Counting
      Kit-8 and Transwell assays. In addition, the expression of LIMD2 was determined
      to be regulated by microRNA (miR)-34a in the present study. RT-qPCR and western
      blot analysis indicated that overexpression of miR-34a notably reduced the mRNA
      and protein expression levels of LIMD2 in H1299 and H549 cells. Additionally, the
      present study reported an inverse correlation between the expression of LIMD2 and
      miR-34a in NSCLC tissues. A luciferase reporter assay also demonstrated that miR
      34a directly targeted the mRNA expression of LIMD2 in NSCLC cells. Finally, miR
      34a was revealed to possess a tumor suppressive role in NSCLC cells.
      Collectively, the results of the present study revealed that LIMD2 promoted NSCLC
      progression and was regulated by miR-34a.

PMID- 30221698
TI  - Theanine, an antitumor promoter, induces apoptosis of tumor cells via the
      mitochondrial pathway.
AB  - Theanine, an active component of green tea (Camellia sinensis), is considered a
      modulator of chemotherapy. To further investigate the anticancer activity of
      theanine, the present study investigated the cytotoxic effect of theanine at the
      concentration of 600 ug/ml, in the human HepG2 hepatoblastoma and HeLa
      adenocarcinoma cell lines, in comparison with the normal L02, H9c2 and HEK293
      cell lines using a MTT assay. It was found that theanine induced cell death in
      the tumor cells, but not in the normal cells. Notably, when glutamine was
      restricted or reduced in the cell culture medium, the cell death induced by
      theanine was significantly enhanced. A terminal deoxynucleotidyl-transferase
      mediated dUTP nick end labeling assay indicated that DNA damage was induced in
      theanine-treated HepG2 cells. Further experiments demonstrated that theanine
      caused HepG2 cell apoptosis through the mitochondrial pathway, with a loss of
      membrane potential and the release of apoptosis-inducing factor, endonuclease G
      and cytochrome c. Western blot analysis and caspase activity detection also
      revealed that caspase-9 and caspase-3 were activated, whereas caspase-8 remained
      inactive. These observations suggested that theanine exerted potent cytotoxicity
      on tumor cells when glutamine was restricted.

PMID- 30221697
TI  - Streptozotocin-induced diabetic mice exhibit reduced experimental choroidal
      neovascularization but not corneal neovascularization.
AB  - The present study aimed to investigate the effects of diabetes mellitus (DM) on
      the generation of experimental corneal neovascularization (CrNV) and choroidal
      neovascularization (ChNV). Diabetes was induced in mice by intraperitoneal
      injection of streptozotocin (STZ). Experimental CrNV and ChNV were induced by
      alkali injury and laser photocoagulation, respectively. CrNV and ChNV were
      compared between the STZ-induced diabetic mice and control mice two weeks after
      injury. Relative expression of angiogenic factors was quantified by reverse
      transcription-quantitative polymerase chain reaction, and progenitor cell or
      macrophage accumulation in the early phase following injury was examined by flow
      cytometric analysis. Compared with the alkali-injured normal mice, the alkali
      injured diabetic mice (STZ-induced) exhibited no significant difference in CrNV
      occurrence, whereas the laser-injured diabetic mice exhibited significantly
      reduced levels of ChNV compared with those of the laser-injured control animals.
      The laser-induced intrachoroidal mRNA expression levels of angiogenic factors,
      including vascular endothelial growth factor, hypoxia-induced factor-1alpha,
      chemokine (C-C motif) ligand 3, and stromal cell-derived factor-1alpha, were
      reduced in the laser-injured diabetic mice when compared with laser-injured
      control mice. Furthermore, the laser-induced intrachoroidal infiltration of c
      Kit+ progenitor cells was impaired in the laser-injured diabetic mice compared
      with the laser-injured control mice. Overall, diabetes did not exert a
      significant effect on the generation of experimental CrNV. However, diabetes
      reduced laser-induced ChNV through downregulation of intrachoroidal progenitor
      cell infiltration and angiogenic factor expression.

PMID- 30221699
TI  - miR-501-3p sensitizes glioma cells to cisplatin by targeting MYCN.
AB  - Cisplatin, a commonly used chemotherapeutic agent for glioma patients, treatment
      often leads to chemoresistance. Accumulating evidence has demosntrated that
      microRNA (miRNA/miR) is involved in drug resistance of glioma cells.
      Nevertheless, the role of miR-501-3p in glioma cell resistance to cisplatin is
      unclear. In the present study, it was revealed that miR-501-3p expression was
      decreased in glioma tissues and further underexpressed in cisplatin-resistant
      glioma cells compared with wild-type (WT) glioma cells. Furthermore, cisplatin
      treatment inhibited the level of miR-501-3p in a time-dependent way. Ectopic
      expression of miR-501-3p suppressed glioma cell growth and invasion, but
      increased cisplatin-resistant glioma cell apoptosis. Furthermore, miR-501-3p
      sensitized glioma cells to cisplatin-induced proliferation arrest and death.
      Mechanistically, it was demonstrated that miR-501-3p targeted MYCN in glioma
      cells. In addition, it was revealed that miR-501-3p inhibited MYCN expression by
      a luciferase reporter assay and reverse transcription-quantitative polymerase
      chain reaction. Notably, restoration of MYCN reversed the effects of miR-501-3p
      in cisplatin-resistant glioma cells. In conclusion, these results suggested that
      miR-501-3p may serve a promising marker for cisplatin resistance.

PMID- 30221700
TI  - Expression and clinical significance of ubiquitin-specific-processing protease 34
      in diffuse large B-cell lymphoma.
AB  - Ubiquitin-specific-processing protease 34 (USP34) is a deubiquitinase that is
      involved in the pathogenesis of various cancers. Its roles in diffuse large B
      cell lymphoma (DLBCL) are unknown. The present study aimed to determine the level
      of USP34 expression and to explore its association with clinicopathological
      features and prognosis in patients with DLBCL; a total of 30 cases of reactive
      lymphoid hyperplasia and 131 cases of DLBCL were included in this study. The
      level of USP34 expression was examined by immunohistochemistry (IHC), and
      correlations between USP34 expression and clinicopathological features and
      prognosis were analyzed. In addition, mutations, expression and clinical
      significance of USP34 in DLBCL were evaluated using data from The Cancer Genome
      Atlas (TCGA). USP34 expression was significantly higher in DLBCL compared with
      expression in reactive lymphoid hyperplasia. In DLBCL, overexpression of USP34
      was associated with older age, germinal center B cell-like (GCB) subtype,
      multiple extranodal involvements and higher International Prognostic Index (IPI)
      scores. No significant association was identified between USP34 protein level and
      patient survival. In the TCGA dataset, low USP34 mRNA expression was demonstrated
      to be associated with a poor disease-free survival (DFS), but not with overall
      survival (OS) in patients with DLBCL. In conclusion, high expression of USP34
      protein in DLBCL was associated with older age, GCB subtype, multiple extranodal
      involvement and high IPI scores of DLBCL. USP34 may be a valuable marker for the
      assessment of patients with DLBCL, and further studies are needed to clarify
      USP34 expression on DLBCLs.

PMID- 30221702
TI  - Attenuated endothelial function is associated with decreased endothelial
      progenitor cells and nitric oxide in premenopausal diabetic women.
AB  - Previous studies have demonstrated that the deleterious effect of diabetes
      mellitus (DM) on the risk of cardiovascular disease also occurs in premenopausal
      women, in spite of their relatively high estrogen levels; however, the underlying
      mechanism remains unclear. The present study aimed to investigate the sex-related
      differences in circulating endothelial progenitor cells (EPCs) in a relatively
      young population with type 2 DM (T2DM) and its underlying mechanism. The number
      and functional activity of circulating EPCs, and vascular endothelial function
      assessed using flow-mediated dilation (FMD), were compared in premenopausal women
      and age-matched men with or without T2DM. Nitric oxide (NO) in the plasma or NO
      secreted by EPCs was also measured. The number and activity of circulating EPCs,
      and NO levels in the plasma or culture medium, were lower in premenopausal women
      with T2DM compared with those without T2DM. In addition, the number and activity
      of circulating EPCs and NO levels were decreased in men with T2DM compared with
      in age-matched premenopausal women with T2DM. FMD was positively correlated with
      the number and activity of circulating EPCs, and NO levels. In conclusion, DM in
      premenopausal women may significantly impair the repair capability of EPCs and
      lead to endothelial dysfunction, which may be associated with reduced NO
      production. In patients with both DM and normal glucose tolerance, sex-related
      differences of EPCs are presented in a young population.

PMID- 30221701
TI  - BACE1 gene silencing alleviates isoflurane anesthesia-induced postoperative
      cognitive dysfunction in immature rats by activating the PI3K/Akt signaling
      pathway.
AB  - Postoperative cognitive dysfunction (POCD) is a severe complication characterized
      by cognitive dysfunction following anesthesia and surgery. The aim of the present
      study was to investigate the effects of beta-site amyloid precursor protein
      cleavage enzyme 1 (BACE1) gene silencing on isoflurane anesthesia-induced POCD in
      immature rats via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)
      signaling pathway. Rat models were established and then transfected with BACE1
      small interfering RNA and wortmannin (an inhibitor of PI3K). Blood gas analysis
      was performed, and a series of behavioral experiments were conducted to evaluate
      the cognitive function, learning ability and locomotor activity of rats. Reverse
      transcription quantitative polymerase chain reaction and western blot analysis
      were employed to determine the mRNA and protein expression of the associated
      genes. An ELISA was used to detect the inflammatory indicators and the content of
      amyloid precursor protein (APP) and amyloid-beta (Abeta). Apoptosis of the
      hippocampal CA1 region was observed by terminal deoxynucleotidyl transferase dUTP
      nick-end labeling staining. Initially, it was revealed that the percentage of
      stagnation time in rats was increased by BACE1 gene silencing; the escape latency
      and swimming distance were markedly reduced from the 4th to the 6th day, the time
      the rats spent in first passing the target area was shortened, and the times of
      passing the target area were increased by BACE1 gene silencing, demonstrating
      that BACE1 gene silencing enhanced the spatial memory ability of rats.
      Additionally, it was determined that silencing BACE1 improved the pathological
      state induced by isoflurane anesthesia in immature rats, and attenuated the
      inflammatory response and the levels of APP and Abeta in hippocampal tissues.
      Furthermore, it was suggested that silencing BACE1 may have promoted the
      activation of the PI3K/Akt signaling pathway, thereby inhibiting the apoptosis of
      the hippocampal CA1 region. Taken together, these results indicated that BACE1
      gene silencing may improve isoflurane anesthesia-induced POCD in immature rats by
      activating the PI3K/Akt signaling pathway and inhibiting the Abeta generated by
      APP.

PMID- 30221703
TI  - Molecular pathogenesis involved in human idiopathic pulmonary fibrosis based on
      an integrated microRNA-mRNA interaction network.
AB  - Idiopathic pulmonary fibrosis (IPF) is considered to be an ailment of the lungs
      that cannot be cured, wherein the lung tissues are characterized by increased
      thickness and stiffness, and/or scars. Despite the fact that extensive success
      has been achieved regarding the molecular diagnostics and pathobiology, the basic
      pathogenesis associated with IPF has not yet been fully elucidated and requires
      further clarification. In the current research, the changes in microRNA (miRNA)
      and mRNA expression in IPF were investigated through an integrative network
      technique. The authentic miRNA and mRNA expression profiling datasets were
      downloaded from Gene Expression Omnibus, followed by identification of
      differentially expressed miRNAs and mRNAs with use of the Significance Analysis
      of Microarrays algorithm. Expansion of the molecular targets associated with
      miRNAs was performed with the use of CyTargetLinker in Cytoscape, which was
      succeeded by validation with the use of mRNA array expression profiling. The
      incorporated miRNA-mRNA network covered 27 genes, in addition to 22 miRNAs that
      were associated with IPF development. As revealed by the functional enrichment
      analysis, the cytokine-cytokine receptor interaction and glycine, serine and
      threonine metabolism signalling pathways were extensively associated with IPF
      development. Overall, the present incorporated network illustrated the key link
      between miRNA and genes in IPF; in particular, it was elucidated that miR-409-5p
      and has-miR-376c, together with their target genes (C-C motif chemokine ligand 20
      and oncostatin M), are likely candidates involved in the promotion of IPF
      initiation and progression.

PMID- 30221705
TI  - Sevoflurane-induced neurotoxicity is driven by OXR1 post-transcriptional
      downregulation involving hsa-miR-302e.
AB  - Sevoflurane is a common anesthetic agent used in surgical settings and previous
      studies have indicated that it exerts a neurotoxic effect. However, the molecular
      mechanism underlying this side effect is unknown. In addition, the human microRNA
      302 (hsa-miR-302) family members have been reported to be involved in neuronal
      cell development and biology. Thus, the present study aimed to investigate the
      potential implication of hsa-miR-302e in the sevoflurane-induced cytotoxicity on
      human hippocampal cells (HN-h). HN-h cells were transfected with hsa-miR-302e
      mimic, hsa-miR-302e inhibitor or negative controls and subsequently exposed to
      different concentrations of sevoflurane. An MTT assay was used to assess the
      cytotoxicity of sevoflurane on HN-h cells. Cell apoptosis was determined by flow
      cytometry. The levels of lactate dehydrogenase release, reactive oxygen species,
      lipid peroxidation and intracellular calcium (Ca2+) were additionally detected.
      Reverse transcription-quantitative polymerase chain reaction and western blotting
      were conducted to determine mRNA and protein expression, respectively. A
      luciferase assay was performed for validating the targeting of OXR1 by hsa-miR
      302e. The results indicated that sevoflurane induced a decrease in cell
      viability, malondialdehyde and reactive oxygen species production, lactate
      dehydrogenase release, intracellular Ca2+ production, calcium/calmodulin
      dependent protein kinase II phosphorylation and apoptosis. In addition, treatment
      with sevoflurane induced the expression of hsa-miR-302e while the expression of
      its target, oxidation resistance gene 1 (OXR1), was significantly downregulated.
      Inhibition of hsa-miR-302e expression protected neuronal cells from sevoflurane
      cytotoxicity. Mechanistic studies demonstrated that OXR1 was a direct target of
      hsa-miR-302e. Furthermore, the overexpression of OXR1 abolished the effect of
      sevoflurane on neuronal cells. The results of the present study indicated that
      sevoflurane exerts its neurotoxic effect by regulating the hsa-miR-302e/OXR1
      axis. Therefore, the manipulation of the hsa-miR-302e/OXR1 pathway will be useful
      for preventing sevoflurane-induced neurotoxicity.

PMID- 30221704
TI  - Comparing the role of Ginkgolide B and Ginkgolide K on cultured astrocytes
      exposed to oxygen-glucose deprivation.
AB  - Ginkgolide B (GB) and ginkgolide K (GK) are two main active monomers of
      ginkgolides that present a unique group of diterpenes found naturally in the
      leaves of the Ginkgo biloba tree. Astrocytes are the most abundant cell type
      within the central nervous system (CNS) and serve essential roles in maintaining
      healthy brain function. The present study compared the biological effects of GB
      and GK on astrocytes exposed to oxygen-glucose deprivation (OGD). The results
      demonstrated that GB and GK exhibit many different actions. The level of the
      platelet-activating factor (PAF) was elevated on astrocytes exposed to OGD, and
      inhibited by GB and GK treatment. Although GB and GK inhibited the expression of
      p-NF-kappaB/p65, GK exerted stronger anti-inflammatory and antioxidant effects on
      astrocytes exposed to OGD than GB by inhibiting interleukin (IL)-6 and tumor
      necrosis factor-alpha, and inducing IL-10 and the nuclear factor-erythroid 2
      related factor 2/HO-1 signaling pathway. When compared with GB treatment, GK
      treatment maintained high levels of phosphoinositide 3-kinase/phosphorylated
      protein kinase B expression, and induced a marked upregulation of Wnt family
      member 1 and brain derived neurotrophic factor, indicating that GK, as a natural
      plant compound, may have more attractive prospects for clinical application in
      the treatment of neurological disorders than GB.

PMID- 30221706
TI  - Roles of endoplasmic reticulum stress and autophagy on H2O2-induced oxidative
      stress injury in HepG2 cells.
AB  - Endoplasmic reticulum stress (ERS) can be induced by a variety of physiological
      and pathological factors including oxidative stress, which triggers the unfolded
      protein response to deal with ERS. Autophagy has been hypothesized to be a means
      for tumor cells to increase cell survival under conditions of hypoxia, metabolic
      stress and even chemotherapy. Although they may function independently from each
      other, there are also interactions between responses to oxidative stress injury
      induced by pathologic and pharmacological factors. The aim of the present study
      was to investigate the effects of ERS and autophagy on H2O2-induced oxidative
      stress injury in human HepG2 hepatoblastoma cells. It was demonstrated that
      exposure of HepG2 cells to H2O2 decreased cell viability and increased reactive
      oxygen species (ROS) levels in a dosage-dependent manner. In addition, apoptosis
      and autophagy rates were elevated and reduced following cell exposure to H2O2 +
      the ERS inducer Tunicamycin (TM), and to H2O2 + the ERS inhibitor Salubrinal
      (SAL), compared with the cells treated with H2O2 alone, respectively. Further
      studies revealed that TM enhanced the expression of ERS-related genes including
      glucose-regulated protein-78/binding immunoglobulin protein, inositol-requiring
      kinase-I and activating transcription factor 6 and C/EBP-homologous protein 10,
      which were attenuated by SAL compared with cells exposed to H2O2 alone. The data
      from the present study also demonstrated that LC3II/LC3-I and p62, members of
      autophagy-related genes, were increased and decreased in cells treated with H2O2
      + TM compared with cells treated with H2O2, respectively, indicating that
      autophagy was stimulated by ERS. Furthermore, a reduction in the levels of pro
      caspase-3 and pro caspase-9, and elevation level of caspase-12 were observed in
      cells exposed to H2O2 + TM compared with cells treated with H2O2, respectively,
      suggesting apoptosis induced by H2O2 was enhanced by ERS or autophagy triggered
      by H2O2. The above results suggest that the ERS inducer may be a potential target
      for pharmacological intervention targeted to ERS or autophagy to enhance
      oxidative stress injury of tumor cells induced by antitumor drugs.

PMID- 30221708
TI  - Amino acid starvation promotes podocyte autophagy through mammalian target of
      rapamycin inhibition and transcription factor EB activation.
AB  - Autophagy is important for maintaining normal physiological functions and
      podocyte cell homeostasis. Amino acid signaling is an important upstream
      signaling pathway for autophagy regulation. However, the function and the
      associated mechanism of amino acid signaling in podocyte autophagy is unclear.
      The present study used normal culture medium and amino acid deprivation medium to
      culture podocytes in vitro. Multiple methods were utilized to detect autophagic
      activity including western blot analysis to measure the levels of microtubule
      associated protein 1 light chain 3 (LC3) II and beclin1, reverse transcription
      quantitative polymerase chain reaction was performed to evaluate the levels of
      LC3 mRNA and transmission electron microscopy was conducted to observe
      autophagosomes. In addition, tandem green fluorescent protein (GFP)-monomeric red
      fluorescent protein (mRFP)-LC3 adenoviruses were employed to transduce podocytes
      to observe autophagic flux. Furthermore, the present study examined the effects
      of amino acid signaling on mammalian target of rapamycin (mTOR) activity and the
      nuclear translocation of transcription factor EB (TFEB), a core regulator of
      autophagy, using western blotting and immunofluorescence. The results revealed
      that amino acid starvation promoted the expression of LC3II and beclin1, and
      increased the number of autophagosomes and autolysosomes. Amino acid starvation
      inhibited mTOR activity, and promoted nuclear translocation and TFEB activity.
      Inhibition of TFEB blocked amino acid starvation-induced autophagy. These results
      indicated that amino acid starvation stimulated podocyte autophagy, and thus
      suggested that mTOR suppression and TFEB activation may mediate amino acid
      starvation-induced autophagy in podocytes.

PMID- 30221709
TI  - Structure-activity associations in novel farrerol derivatives with vasorelaxant
      properties.
AB  - To detect the structure-activity associations of farrerol derivatives, the
      relaxation activity of farrerol derivatives was observed in isolated aortic rings
      pre-contracted using phenylephrine in Sprague-Dawley rats. All compounds tested
      in the present study produced a relaxation effect, which was significantly
      affected by the molecular structure. Using a collagen gel contraction assay, the
      present study further evaluated the inhibitiory effect of farrerol derivatives in
      a decreased collagen gel area, induced by Angiotensin II. The results indicated
      that farrerol derivatives could inhibit collagen contraction, and that the
      inhibitory effect was associated with the molecular structure of the compounds.
      Furthermore, the inhibitory strength of the different compounds was consistent
      with the results of vascular tension detection. The activity of the farrerol
      derivatives was closely associated with the molecular structure. The analysis
      indicated that an electron-withdrawing substituent in the ortho position of the
      phenyl group (ring B) was crucial in order to observe improved vasorelaxation
      activity, whereas a hydroxyl or methoxy group was unfavorable. A para electron
      donating group was oberved to increase compound activity. In addition, when the B
      ring was heterocycle rather than a phenyl ring, the vasorelaxation ability was
      weakened.

PMID- 30221707
TI  - Angiotensin II upregulates cyclophilin A by enhancing ROS production in rat
      cardiomyocytes.
AB  - Angiotensin II (Ang II) is a principal molecule of the renin-angiotensin system,
      which promotes hypertrophy and fibrosis. It has been demonstrated that Ang II
      upregulates the expression of cyclophilin A (CypA), which is a potential
      myocardial hypertrophy factor. However, the mechanisms by which Ang II induces
      the expression of CypA in cardiomyocytes remain unclear. In the present study,
      reactive oxygen species (ROS) were detected by fluorescence microscopy, and
      western blot analysis and ELISA were used to measure CypA expression. It was
      identified that Ang II enhanced the production of ROS in rat cardiomyocytes. ROS,
      in turn, promoted CypA expression and secretion. Notably, the action of Ang II
      was primarily dependent on the angiotensin type 2 receptor (AT2R), not the type 1
      receptor. These results provided an insight into the role of the AT2R signaling
      pathway in Ang II-induced myocardial hypertrophy.

PMID- 30221710
TI  - Using Illumina Infinium HumanMethylation 450K BeadChip to explore genome-wide DNA
      methylation profiles in a human hepatocellular carcinoma cell line.
AB  - Aberrant DNA methylation is the most common type of epigenetic alteration and is
      associated with many types of cancer. Although previous studies have provided a
      few novel DNA methylation markers in hepatocellular carcinoma (HCC), specific DNA
      methylation patterns and comparisons of the aberrant alterations in methylation
      between HCC and normal liver cell lines have not yet been reported. Therefore, in
      the present study the Illumina Infinium HumanMethylation 450K BeadChip was
      employed to identify the genome-wide aberrant DNA methylation profiles of Huh7
      and L02 cells. Following Bonferroni adjustment, 102,254 differentially methylated
      CpG sites (covering 26,511 genes) were detected between Huh7 and L02 cells. Of
      those CpG sites, 62,702 (61.3%) sites were hypermethylated (covering 12,665
      genes) and 39,552 (38.7%) sites were hypomethylated (covering 13,846 genes). The
      results of the present study indicated that 40.3% of the CpG sites were in CpG
      island regions, 20.7% were in CpG shores and 8.8% were in shelf regions. A total
      of 57.3% hypermethylated CpG sites and 39.4% of the hypomethylated CpG sites had
      a |beta-Difference| >=50%. Within the significant differentially methylated CpG
      sites, 490 genes were located within 598 differentially methylated regions. Gene
      Ontology enrichment analysis revealed that 2,107 differentially methylated genes
      were associated with 'biological process', 13,351 differentially methylated genes
      were associated with 'molecular function', and 18,041 differentially methylated
      genes were associated with 'cellular component'. Kyoto Encyclopedia of Genes and
      Genomes pathway-based analysis revealed 43 signaling pathways that were
      associated with 5,195 differentially methylated genes. These results demonstrated
      that aberrant DNA methylation may be a key and common event underlying the
      tumorigenesis of Huh7 cells. The present study also identified many subsets of
      hypo- or hyper-methylated CpG sites, genes and signaling pathways, which have an
      importance in the occurrence and development of HCC.

PMID- 30221711
TI  - Protective effects of alpha-2-macroglobulin on human bone marrow mesenchymal stem
      cells in radiation injury.
AB  - Osteoradionecrosis of the jaws (ORNJ) is a complication of oral and maxillofacial
      malignancy that arises following radiotherapy; progressive jaw necrosis severely
      decreases the quality of life of patients. Human bone marrow mesenchymal stem
      cells (hBMMSCs) are a cell type with self-renewal and pluripotent differentiation
      potential in the bone marrow stroma. These cells are associated with bone tissue
      regeneration and are one of the primary cell types affected by bone tissue
      radiation injury. alpha-2-macroglobulin (alpha2M) is a glycoprotein-rich
      macromolecule that interacts with cytokines, growth factors and hormones to serve
      a variety of biological roles. In addition, alpha2M possesses radio-protective
      effects. The aim of the present study was to investigate whether alpha2M has
      protective effects against radiation injury of hBMMSCs. Cell counting kit-8 and
      colony formation assays were used to monitor cell proliferation. Western blot
      analysis and reverse transcription-quantitative polymerase chain reaction were
      used to detect Beclin1, microtubule-associated protein 1A/1B, sex determining
      region Y, Nanog, runt-related transcription factor 2, osteoglycin and manganese
      superoxide dismutase expression. The formation of calcium nodules was evaluated
      by Alizarin red staining after osteogenic induction. Flow cytometric analysis of
      Annexin-V and propidium iodide double staining was used to detect changes in
      apoptosis rate. Alkaline phosphatase and superoxide dismutase activity were
      determined using colorimetric assays. Reactive oxygen species levels were
      detected using 2',7'-dichlorodihydrofluorescein diacetate. The results of the
      present study revealed that alpha2M increased the rate of proliferation, reduced
      autophagy, alleviated pluripotent differentiation injury, increased the
      osteogenic differentiation ability and decreased the rate of apoptosis in hBMMSCs
      following irradiation via an antioxidative pathway. In conclusion, alpha2M
      exhibited protective effects against radiation injury in hBMMSCs and may be
      considered a potential therapeutic agent for the prevention and treatment of
      ORNJ.

PMID- 30221712
TI  - Celastrol inhibits glucocorticoid-induced osteoporosis in rat via the PI3K/AKT
      and Wnt signaling pathways.
AB  - Modern pharmacological studies revealed that Celastrol exhibits anti
      inflammation, anti-bacteria, anti-virus, anti-fertility, insect-resistance
      functions and has been used for the treatment of rheumatism, rheumatoid
      arthritis, blood diseases, skin diseases and agricultural insecticide. The
      present study aimed to investigate the effects of Celastrol on glucocorticoid
      induced osteoporosis (GIOP) and the underlying molecular mechanisms. The findings
      of the current study revealed that Celastrol reduced body weight, urine
      calcium/creatinine, tartrate-resistant acid phosphatase 5b, C-terminal
      telopeptide of type I collagen, and induced osteocalcin in GIOP rats. In
      addition, alkaline phosphatase, triiodothyronine receptor auxiliary protein and
      cathepsin K mRNA expression levels were effectively suppressed, and osteocalcin,
      bone morphogenetic protein 2, type I collagen and runt-related transcription
      factor 2 mRNA expression levels were effectively induced in osteoporosis rats
      treated with Celastrol. Celastrol inhibited prostaglandin E2 and caspase-3
      protein expression levels, and induced phosphoinositol 3-kinase (PI3K),
      phosphorylated-protein kinase B (AKT) and glycogen synthase kinase-3
      phosphorylation, Wnt and beta-catenin protein expression in GIOP rats. The
      present study demonstrated that Celastrol may inhibit GIOP in rats via the
      PI3K/AKT and Wnt signaling pathways.

PMID- 30221714
TI  - Epigallocatechin-3-gallate protects against secondary osteoporosis in a mouse
      model via the Wnt/beta-catenin signaling pathway.
AB  - Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound extracted and
      isolated from green tea, which has a variety of important biological activities
      in vitro and in vivo, including anti-tumor, anti-oxidation, anti-inflammation and
      lowering blood pressure. The aim of the present study was to investigate the
      protective effect of EGCG against secondary osteoporosis in a mouse model via the
      Wnt/beta-catenin signaling pathway. Reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) and western blotting were used to analyze runt-related
      transcription factor 2 and osterix mRNA expression, and the protein expression of
      cyclin D1, Wnt and beta-catenin, and suppressed peroxisome proliferator-activated
      receptor gamma protein expression. The protective effect of EGCG against
      secondary osteoporosis was examined and its potential mechanism was analyzed.
      Treatment with EGCG significantly decreased serum calcium, urinary calcium, body
      weight and body fat, and increased leptin levels in mice with secondary
      osteoporosis. In addition, EGCG treatment significantly inhibited the structure
      score of articular cartilage and cancellous bone in proximal tibia metaphysis in
      mice with secondary osteoporosis. Treatment also significantly decreased alkaline
      phosphatase activity, runt-related transcription factor 2 and osterix mRNA
      expression. EGCG also significantly induced the protein expression of cyclin D1,
      Wnt and beta-catenin, and suppressed peroxisome proliferator-activated receptor
      gamma protein expression in mice with secondary osteoporosis. Taken together,
      these results suggest that EGCG may be a possible new drug in clinical settings.

PMID- 30221713
TI  - Genetic mutation of familial dilated cardiomyopathy based on next-generation
      semiconductor sequencing.
AB  - Dilated cardiomyopathy (DCM) is a complex myocardial disease of multifactorial
      etiologies, including enlarged cardiac chambers and contractile dysfunction. It
      has been suggested that the inheritance of DCM-associated mutations predominates
      its onset. Therefore, the present study investigated the pathogenesis of DCM via
      pedigree analysis and genetic diagnosis by massive whole-exome screening, and
      targeted exon capture. To study the familial gene-phenotype association, the exon
      and splice sites of 325 hereditary disease-associated genes in the proband with
      familial dilated cardiomyopathy (FDC), including 61 cardiac disease-associated
      genes, such as the lamins A/C (LMNA), were analyzed by ultra-high multiplex
      polymerase chain reaction and the Ion AmpliSeqTM Inherited Disease Panel. The
      present study also conducted Sanger DNA Sequencing for family members with global
      minor allele frequencies <1% to verify potential pathogenic mutation sites. A
      total of three rare missense mutations were detected, including heterozygous
      c.244G>A in LMNA, c.546C>G in potassium voltage-gated channel subfamily KQT
      (KCNQ4) and c.1276G>A in EYA transcriptional coactivator and phosphatase 1
      (EYA1), indicating a glutamic acid to lysine substitution at amino acid 82
      (p.E82K) in LMNA, a p.F182L in KCNQ4 (a mutation associated with pathogenic
      deafness) and p.G426S in EYA1 (associated with Branchiootorenal syndrome 1 and
      Branchiootic syndrome 1 pathogenesis). In the present study, a carrier with
      slight hearing impairment was detected in the family analyzed; however, no
      patients with deafness or branchiootorenal syndrome were observed. LMNA p.E82K
      revealed SIFT and PolyPhen-2 scores of 0 and 1, respectively. In the second
      generation, 3 patients with DCM underwent permanent pacemaker implantation due to
      sick sinus syndrome, atrioventricular block and unstable cardiac
      electrophysiology. The present study suggested that LMNA p.E82K may contribute to
      the pathogenesis of FDC and concomitant atrioventricular block. At present, only
      three families with DCM resulting from similar mutations have been reported. The
      present study demonstrated the strong pathogenic effects of LMNA p.E82K on DCM.

PMID- 30221715
TI  - miR-3120-5p acts as a diagnostic biomarker in non-small cell lung cancer and
      promotes cancer cell proliferation and invasion by targeting KLF4.
AB  - Accumulating evidence indicates that microRNAs (miRs) are important regulators in
      a number of types of human cancer, including non-small cell lung cancer (NSCLC).
      The function of miR-3120-5p in NSCLC remains unclear. In the present study, it
      was demonstrated that miR-3120-5p was significantly upregulated in NSCLC tissues.
      Additionally, miR-3120-5p expression level was positively associated with NSCLC
      metastasis and tumor, node and metastasis stage. Furthermore, it was demonstrated
      that miR-3120-5p exhibited potential as an indicator of NSCLC for use in
      diagnosis. Through functional experiments, it was demonstrated that
      overexpression of miR-3120-5p promoted the proliferation, colony formation and
      invasion of NSCLC cells. miR-3120-5p overexpression significantly promoted cell
      cycle progression. Mechanistically, it was demonstrated that Krueppel-like factor
      4 (KLF4) was a target of miR-3120-5p in NSCLC cells. Overexpression of miR-3120
      5p repressed the expression of KLF4 in A549 and H460 cells. Furthermore, it was
      demonstrated that KLF4 was downregulated in NSCLC tissues and cell lines.
      Overexpression of KLF4 significantly reversed the effects of miR-3120-5p on NSCLC
      cell proliferation and invasion. In conclusion, the present study demonstrated
      that miR-3120-5p promoted NSCLC progression by directly targeting KLF4.

PMID- 30221716
TI  - miRNA-328 overexpression confers cisplatin resistance in non-small cell lung
      cancer via targeting of PTEN.
AB  - Chemotherapy resistance, the molecular mechanism of which is complex and has not
      been fully understood, poses a major challenge in the treatment of patients with
      non-small cell lung cancer (NSCLC). The dysregulation of microRNAs (miRs) has
      been reported to serve a pivotal role in the development of cancer and drug
      resistance. In the present study, reverse transcription-quantitative polymerase
      chain reaction analysis revealed a significant increase in miR-328 and a
      significant decrease in phosphatase and tensin homolog (PTEN) mRNA expression
      levels within tumor tissues from patients with cisplatin-resistant NSCLC compared
      with those of cisplatin-sensitive NSCLC patients. In addition, there was a
      negative correlation between PTEN mRNA and the miR-328 expression levels. In
      addition, higher miR-328 expression levels, and lower PTEN mRNA and protein
      expression levels, were detected in cisplatin-resistant A549 (A549rCDDP) cells
      when compared with in their parental cells. A549rCDDP cells demonstrated
      significantly higher cell viability compared with A549 cells following treatment
      with all concentrations of cisplatin tested (2, 4, 6 and 8 uM). Additionally,
      transfection of miR-328 inhibitor significantly increased PTEN mRNA and protein
      expression levels. Furthermore, the present study predicted and confirmed PTEN, a
      well-known tumor suppressor, as a direct target of miR-328 in NSCLC cells via the
      online tool MiRanda and a dual luciferase assay, respectively. Cell viability
      assay and flow cytometry analysis demonstrated that inhibition of miR-328 also
      induced cellular apoptosis and decreased cell proliferation in A549rCDDP cells
      treated with cisplatin. In conclusion, these results suggested that abnormal
      expression of miR-328 may contribute to cisplatin resistance in NSCLC, and may be
      considered to be a novel therapeutic target and indicator for the treatment and
      prognosis of patients with NSCLC treated with cisplatin-based chemotherapy.

PMID- 30221717
TI  - Protective effect of berberine on aconite-induced myocardial injury and the
      associated mechanisms.
AB  - Aconitum plants, which have analgesic, diuretic and anti-inflammatory effects,
      have been widely used to treat various types of disease. However, the apparent
      toxicity of Aconitum-derived agents, particularly in the cardiovascular system,
      has largely limited their clinical use. Thus, the present study investigated
      whether berberine (Ber), an isoquinoline alkaloid, may reduce myocardial injury
      induced by aconitine (AC) in rats and the underlying mechanisms. Rats (n=40) were
      randomly divided into four groups: Control, Chuan-wu and Chuan-wu + Ber (8 and 16
      mg/kg doses). Electrocardiograms (ECG) of the rats were recorded and serum
      biomarkers of cardiac function [lactate dehydrogenase (LDH), creatine kinase (CK)
      and CK-MB] were assayed. Histopathological changes were assessed using myocardial
      tissue sectioning and hematoxylin and eosin staining. Additionally, the effects
      of Ber on AC-induced arrhythmias in rats were observed. The changes in ECG
      following AC perfusion were observed, and the types and onset time of arrhythmias
      were analyzed. Furthermore, the effects of Ber and AC on papillary muscle action
      potentials were observed. The results suggested that Ber ameliorated myocardial
      injury induced by Chuan-wu, which was indicated by reduced arrhythmias and
      decreased LDH, CK and CK-MB levels in serum. Furthermore, histological damage,
      including dilation of small veins and congestion, was also markedly attenuated by
      Ber. In addition, the occurrence of arrhythmias was significantly delayed, and
      the dosage of AC required to induce arrhythmias was also increased by Ber
      pretreatment. Additionally, AC-induced changes in action potential amplitude,
      duration of 30% repolarization and duration of 90% repolarization in the
      papillary muscle were attenuated by Ber. All of these results indicate that Ber
      had a preventive effect on acute myocardial injury induced by Chuan-wu and
      arrhythmias caused by AC, which may be associated with the inhibition of delayed
      depolarization and triggered activity caused by AC. Thus, combination treatment
      of Ber with Aconitum plants may be a novel strategy to prevent AC-induced
      myocardial injury in clinical practice.

PMID- 30221718
TI  - Platelet-rich fibrin exudate promotes the proliferation and osteogenic
      differentiation of human periodontal ligament cells in vitro.
AB  - The purpose of the present study was to evaluate the effects of platelet-rich
      fibrin (PRF) exudate on the proliferation, osteogenic differentiation and
      mineralization of human periodontal ligament cells (hPDLCs) in vitro. In the
      present study PRF was obtained with permission, from the peripheral blood of
      healthy donors and PRF exudates were collected on the 7th day of incubation.
      hPDLCs were obtained from healthy premolars, cultured by a tissue explant method
      and identified with anti-vimentin and anti-cytokeratin antibodies. PRF exudates
      were added to hPDLCs in different concentrations to evaluate cell proliferation
      and osteogenic differentiation. The proliferation of hPDLCs was measured using a
      colorimetric assay. Osteogenic differentiation and mineralization were determined
      by Alizarin red staining, alkaline phosphatase activity (ALP), western blotting
      and reverse transcription-quantitative polymerase chain reaction. Cell
      proliferation was enhanced by addition of the PRF exudate, which also promoted
      the formation of mineralized matrix nodules and upregulated ALP activity and
      osteoblast-associated levels of osteocalcin, runt-related transcription factor
      and osterix gene expression. As these stimulatory effects occurred in a dose
      dependent manner, it was concluded that high concentrations of the PRF exudate
      served an essential role in the proliferation, osteogenic differentiation and
      mineralization of hPDLCs in vitro. The present study demonstrated that PRF
      exudate enhanced hPDLC proliferation, induced the osteoblastic differentiation of
      hPDLCs into mineralized tissue-formation cells in vitro, and may therefore
      provide potential benefits for periodontal tissue engineering; contributing to
      the primary processes of periodontal tissue regeneration. From the perspective of
      both economics and biology, PRF has greater clinical benefits than analogous
      growth factors.

PMID- 30221720
TI  - Long non-coding RNA ferritin heavy polypeptide 1 pseudogene 3 controls glioma
      cell proliferation and apoptosis via regulation of the microRNA-224-5p/tumor
      protein D52 axis.
AB  - The aim of the present study was to investigate the potential role and regulatory
      mechanism of long non-coding RNA ferritin heavy polypeptide 1 pseudogene 3
      (FTH1P3) in glioma development. The expression of FTH1P3 in low- and high-grade
      glioma tissues was investigated using reverse transcription-quantitative
      polymerase chain reaction. FTH1P3 expression was overexpressed or suppressed in
      U251 glioma cells to examine the involvement of FTH1P3 in glioma cell
      proliferation and apoptosis using MTT assay and flow cytometry respectively. In
      addition, the regulatory association between FTH1P3, microRNA (miR)-224-5p and
      tumor protein (TP) D52 was investigated to elucidate the potential underlying
      mechanisms of FTH1P3 in glioma by luciferase reporter assay. The results revealed
      that FTH1P3 was up-regulated in glioma tissues, and FTH1P3 expression in high
      grade glioma tissues was significantly higher compared with that in low-grade
      glioma tissues. Upregulation of FTH1P3 promoted glioma cell proliferation and
      inhibited apoptosis. Furthermore, FTH1P3 inhibited miR-224-5p expression, which
      in turn negatively regulated TPD52 expression. Overexpression of miR-224-5p
      significantly inhibited U251 cell proliferation and induced cellular apoptosis;
      this effect was clearly reversed following co-transfection of miR-224-5p and
      TPD52. These data revealed that upregulation of FTH1P3 may have promoted glioma
      cell proliferation and inhibited apoptosis. Thus, the miR-224-5p/TPD52 axis may
      be a downstream mechanism of FTH1P3 in glioma progression. The findings of the
      present study may provide a theoretical basis for the study of the treatment of
      glioma in the future.

PMID- 30221721
TI  - Acute stimulatory effect of tumor necrosis factor on the basolateral 50 pS K
      channels in the thick ascending limb of the rat kidney.
AB  - The aim of the present study was to investigate the acute effect and mechanism of
      tumor necrosis factor (TNF) on basolateral 50 pS K channels in the thick
      ascending limb (TAL) of the rat kidney. The TAL tubules were isolated from the
      rat kidney, and the activity of the 50 pS K channels was recorded using the patch
      clamp technique. The results indicated that the application of TNF (10 nM)
      significantly activated the 50 pS K channels and the TNF effect was concentration
      dependent. Inhibition of protein kinase A, phospholipase A2 and protein tyrosine
      kinase using pathway inhibitors (H89, AACOCF3 and Herbimycin A, respectively) did
      not abolish the stimulatory effect of TNF, indicating that none of these pathways
      mediated the TNF effect. By contrast, the phenylarsine oxide inhibitor against
      protein tyrosine phosphatase (PTP) decreased the activity of the 50 pS K channels
      and blocked the stimulatory effect of TNF on these channels. Furthermore, western
      blot analysis demonstrated that the application of TNF (10 nM) in the TAL
      increased the phosphorylation of PTP, an indication of PTP activity stimulation.
      Thus, it was concluded that the acute application of TNF may stimulate the
      basolateral 50 pS K channel in the TAL and the stimulatory effect of TNF may be
      mediated by the PTP-dependent pathway.

PMID- 30221719
TI  - Network analysis of membranous glomerulonephritis based on metabolomics data.
AB  - Membranous glomerulonephritis (MGN) is one of the most frequent causes of
      nephrotic syndrome in adults. It is characterized by the thickening of the
      glomerular basement membrane in the renal tissue. The current diagnosis of MGN is
      based on renal biopsy and the detection of antibodies to the few podocyte
      antigens. Due to the limitations of the current diagnostic methods, including
      invasiveness and the lack of sensitivity of the current biomarkers, there is a
      requirement to identify more applicable biomarkers. The present study aimed to
      identify diagnostic metabolites that are involved in the development of the
      disease using topological features in the component-reaction-enzyme-gene (CREG)
      network for MGN. Significant differential metabolites in MGN compared with
      healthy controls were identified using proton nuclear magnetic resonance and gas
      chromatography-mass spectrometry techniques, and multivariate analysis. The CREG
      network for MGN was constructed, and metabolites with a high centrality and a
      striking fold-change in patients, compared with healthy controls, were introduced
      as putative diagnostic biomarkers. In addition, a protein-protein interaction
      (PPI) network, which was based on proteins associated with MGN, was built and
      analyzed using PPI analysis methods, including molecular complex detection and
      ClueGene Ontology. A total of 26 metabolites were identified as hub nodes in the
      CREG network, 13 of which had salient centrality and fold-changes: Dopamine,
      carnosine, fumarate, nicotinamide D-ribonucleotide, adenosine monophosphate,
      pyridoxal, deoxyguanosine triphosphate, L-citrulline, nicotinamide,
      phenylalanine, deoxyuridine, tryptamine and succinate. A total of 13 subnetworks
      were identified using PPI analysis. In total, two of the clusters contained seed
      proteins (phenylalanine-4-hydroxlylase and cystathionine gamma-lyase) that were
      associated with MGN based on the CREG network. The following biological processes
      associated with MGN were identified using gene ontology analysis: 'Pyrimidine
      containing compound biosynthetic process', 'purine ribonucleoside metabolic
      process', 'nucleoside catabolic process', 'ribonucleoside metabolic process' and
      'aromatic amino acid family metabolic process'. The results of the present study
      may be helpful in the diagnostic and therapeutic procedures of MGN. However,
      validation is required in the future.

PMID- 30221723
TI  - Association between the methylation of six apoptosis-associated genes with autism
      spectrum disorder.
AB  - Excessive apoptosis hinders the process of brain maturation and is regarded as
      one of the principal risk factors for the development of autism spectrum disorder
      (ASD). The aim of the present study was to investigate the association between
      the methylation of six apoptosis-associated genes [transforming growth factor
      beta 1 (TGFB1), BCL2 associated X, apoptosis regulator, insulin like growth
      factor binding protein 3, protein kinase C beta 1, presenilin 2 and C-C motif
      chemokine ligand 2] and ASD. Using quantitative methylation-specific polymerase
      chain reaction technology, DNA methylation levels were detected in 42 autistic
      and 26 control subjects. The logistic regression analysis results demonstrated
      that of the six genes, only TGFB1 was significantly hypomethylated in peripheral
      blood samples from children with autism compared with control samples (mean
      percentage of methylated reference, 0.011% vs. 0.019%; age-adjusted P=0.028). In
      addition, TGFB1 methylation was identified to be positively associated with the
      interaction ability score from the Autism Behavior Checklist (r=0.452; P=0.035).
      These data suggested that decreased TGFB1 methylation may contribute to the
      development of ASD.

PMID- 30221722
TI  - FKBP11 protects intestinal epithelial cells against inflammation-induced
      apoptosis via the JNK-caspase pathway in Crohn's disease.
AB  - Endoplasmic reticulum (ER) stress in intestinal epithelial cells (IECs) has an
      important role in the pathogenesis of Crohn's disease (CD). FK506 binding protein
      11 (FKBP11), a member of the peptidyl-prolyl cis-trans isomerase family, is
      involved in the unfolded protein response (UPR) and is closely associated with
      inflammation. Previous bioinformatics analysis revealed a potential association
      between FKBP11 and human CD. Thus, the present study aimed to investigate the
      potential significance of FKBP11 in IEC homeostasis and CD. In the present study,
      increased expression of FKBP11 was detected in the intestinal inflammatory
      tissues of patients with CD. Furthermore, the results of the present study
      revealed that overexpression of FKBP11 was accompanied by increased expression
      levels of the ER stress marker 78 kDa glucose-regulated protein in the colon
      tissues of a 2, 4, 6-trinitrobenzenesulphonic acid-induced mouse colitis model.
      Using interferon-gamma (IFN-gamma)/tumor necrosis factor-alpha (TNF-alpha)
      stimulated IECs as an ER stress and apoptosis cell model, the associated of
      FKBP11 with ER stress and apoptosis levels was confirmed in IECs. Overexpression
      of FKBP11 was revealed to significantly attenuate the elevated expression of pro
      apoptotic proteins (Bcl2 associated X apoptosis regulator, caspase-12 and active
      caspase-3), suppress the phosphorylation of c-Jun N-terminal kinase (JNK), and
      decrease apoptosis of IFN-gamma/TNF-alpha stimulated IECs. Knockdown of FKBP11 by
      transfection with small interfering RNA further validated the aforementioned
      results. In conclusion, these results suggest that the UPR protein FKBP11 may
      protect IECs against IFN-gamma/TNF-alpha induced apoptosis by inhibiting the ER
      stress-associated JNK/caspase apoptotic pathway in CD.

PMID- 30221724
TI  - [Corrigendum] Neurotoxin beta-N-methylamino-L-alanine induces endoplasmic
      reticulum stress-mediated neuronal apoptosis.
AB  - Following the publication of the above article and a Corrigendum published in
      July 2018, the authors have noted an additional error, associated with the
      presentation of Fig. 1C. Fig 1C showed that beta-N-methylamino-L-alanine induces
      neuronal apoptotic cell death; however, an error was made in the compilation of
      this figure and an incorrect band image was selected for alpha-actinin, the
      loading control panel for Fig. 1C. A corrected version of Fig. 1 is shown
      opposite, incorporating the correct alpha-actinin protein bands in Fig. 1C. This
      change affects neither the interpretation of the data nor conclusions of this
      work. We regret that this further error went unnoticed at the time, and thank the
      Editor for allowing us the opportunity to publish this additional Corrigendum.
      [the original article was published in the Molecular Medicine Reports 14: 4873
      4880, 2016; DOI: 10.3892/mmr.2016.5802].

PMID- 30221725
TI  - Adoptive transfer of xenoantigen-stimulated T cell receptor Vbeta-restricted
      human regulatory T cells prevents porcine islet xenograft rejection in humanized
      mice.
AB  - Polyclonal expansion of human regulatory T cells (Tregs) prevents xenogeneic
      rejection by suppressing effector T cell responses in vitro and in vivo. However,
      a major limitation to using polyclonally expanded Tregs is that they may cause
      pan-immunosuppressive effects. The present study was conducted to compare the
      ability of ex vivo expanded human xenoantigen-stimulated Tregs (Xeno-Treg) and
      polyclonal Tregs (Poly-Treg) to protect islet xenografts from rejection in NOD
      SCID interleukin (IL)-2 receptor (IL2r)gamma-/- mice. Human cluster of
      differentiation (CD)4+CD25+CD127lo Tregs, expanded either by stimulating with
      porcine peripheral blood mononuclear cells (PBMCs) or anti-CD3/CD28 beads, were
      characterized by immune cell phenotyping, T cell receptor (TCR) Vbeta CDR3
      spectratyping and performing suppressive activity assays in vitro. The efficiency
      of adoptively transferred ex vivo human Tregs was evaluated in vivo using
      neonatal porcine islet cell clusters (NICC) transplanted into NOD-SCID IL-2rgamma
      /- mice, which received human PBMCs with or without Xeno-Treg or Poly-Treg. Xeno
      Treg, which expressed increased levels of human leukocyte antigen-DR and secreted
      higher levels of IL-10, demonstrated enhanced suppressive capacity in a pig-human
      mixed lymphocyte reaction. Spectratypes of TCR Vbeta4, Vbeta10, Vbeta18 and
      Vbeta20 in Xeno-Treg showed restriction and expanded clones at sizes of 205, 441,
      332 and 196 respectively, compared to those of Poly-Treg. Reconstitution of mice
      with human PBMCs and Poly-Treg resulted in NICC xenograft rejection at 63 days.
      Adoptive transfer with human PBMCs and Xeno-Treg prolonged islet xenograft
      survival beyond 84 days, with grafts containing intact insulin-secreting cells
      surrounded by a small number of human CD45+ cells. This study demonstrated that
      adoptive transfer of ex vivo expanded human Xeno-Treg may potently prevent islet
      xenograft rejection in humanized NOD-SCID IL2rgamma-/- mice compared with Poly
      Treg. These findings suggested that adoptive Treg therapy may be used for
      immunomodulation in islet xenotransplantation by minimizing systemic
      immunosuppression.

PMID- 30221596
TI  - Effect of Aspirin on Disability-free Survival in the Healthy Elderly.
AB  - BACKGROUND: Information on the use of aspirin to increase healthy independent
      life span in older persons is limited. Whether 5 years of daily low-dose aspirin
      therapy would extend disability-free life in healthy seniors is unclear. METHODS:
      From 2010 through 2014, we enrolled community-dwelling persons in Australia and
      the United States who were 70 years of age or older (or >=65 years of age among
      blacks and Hispanics in the United States) and did not have cardiovascular
      disease, dementia, or physical disability. Participants were randomly assigned to
      receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary
      end point was a composite of death, dementia, or persistent physical disability.
      Secondary end points reported in this article included the individual components
      of the primary end point and major hemorrhage. RESULTS: A total of 19,114 persons
      with a median age of 74 years were enrolled, of whom 9525 were randomly assigned
      to receive aspirin and 9589 to receive placebo. A total of 56.4% of the
      participants were women, 8.7% were nonwhite, and 11.0% reported previous regular
      aspirin use. The trial was terminated at a median of 4.7 years of follow-up after
      a determination was made that there would be no benefit with continued aspirin
      use with regard to the primary end point. The rate of the composite of death,
      dementia, or persistent physical disability was 21.5 events per 1000 person-years
      in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard
      ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). The rate of
      adherence to the assigned intervention was 62.1% in the aspirin group and 64.1%
      in the placebo group in the final year of trial participation. Differences
      between the aspirin group and the placebo group were not substantial with regard
      to the secondary individual end points of death from any cause (12.7 events per
      1000 person-years in the aspirin group and 11.1 events per 1000 person-years in
      the placebo group), dementia, or persistent physical disability. The rate of
      major hemorrhage was higher in the aspirin group than in the placebo group (3.8%
      vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). CONCLUSIONS:
      Aspirin use in healthy elderly persons did not prolong disability-free survival
      over a period of 5 years but led to a higher rate of major hemorrhage than
      placebo. (Funded by the National Institute on Aging and others; ASPREE
      ClinicalTrials.gov number, NCT01038583 .).

PMID- 30221726
TI  - Silencing of pantothenate kinase 2 reduces endothelial cell angiogenesis.
AB  - Coenzyme A (CoA) is an essential cofactor of cellular metabolism that is involved
      in ~4% of cellular reactions. Its de novo production relies on five subsequent
      enzymatic steps, starting with the phosphorylation of vitamin B5. Pantothenate
      kinase 2 (PANK2) and coenzyme A synthase (COASY) catalyze the first and last
      steps of this pathway. Mutations in these genes lead to severe and progressive
      movement disorders, with neurodegeneration and iron accumulation in the basal
      ganglia, known as PANK2- and COASY protein-associated neurodegeneration,
      respectively. Given the ubiquitous role of CoA in cellular metabolism, it is
      still not clear why patients carrying PANK2 and COASY mutations develop almost
      exclusively neurological symptoms. Important clues are the energetic profile of
      neural cells as well as the high levels of PANK2 expression in the brain;
      however, other features may contribute to this selective tissue vulnerability.
      Notably, when pank2 or coasy expression was suppressed in zebrafish evident
      perturbation of neuronal development was observed, as well as severe defects in
      vasculature formation. Supplementation of CoA to fish water prevented the
      appearance of the phenotype, thereby confirming the specific connection with the
      availability of the metabolic cofactor. The present study investigated the
      associations between PANK2 defects and angiogenesis in a mammalian setting, and
      revealed that PANK2 expression was required for normal angiogenetic properties of
      human umbilical vein endothelial cells.

PMID- 30221727
TI  - Effect of chemokine CC ligand 2 (CCL2) on alpha-synuclein-induced microglia
      proliferation and neuronal apoptosis.
AB  - The present study aimed to investigate the effect of chemokine CC ligand 2 (CCL2)
      on alpha-synuclein-mediated microglia proliferation and neuronal apoptosis.
      Primary cultured microglia and primary neurons were isolated and cultured in
      vitro. Microglia were divided into four groups: The cells in the control group
      were treated with an identical amount of PBS, whereas the cells in the CCL2 group
      were cultured in medium containing 0.05 ng/ul CCL2; cells in the alpha-synuclein
      group were treated with medium containing 0.2 ng/ul alpha-synuclein; and cells in
      the CCL2 plus alpha-synuclein group were cultured in medium containing 0.05 ng/ul
      CCL2 and 0.2 ng/ul alpha-synuclein. After incubation for 24 h, the proliferation
      of glial cells, and the level of alpha-synuclein in the cells, were measured. The
      levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta)
      and nitric oxide (NO) in the culture medium were also measured. Levels of cleaved
      caspase-3, Akt and phosphorylated (p)-Akt in neurons treated with primary
      microglia culture medium in each group were subsequently monitored. The
      proliferation activity and secretion of TNF-alpha, IL-1beta and NO in the CCL2,
      alpha-synuclein and CCL2 plus alpha-synuclein groups were significantly higher
      compared with that in the control group (P<0.05), as were the levels of alpha
      synuclein (P<0.01). The levels of neuronal apoptosis and cleaved caspase-3
      protein in the CCL2, alpha-synuclein and CCL2 plus alpha-synuclein groups were
      also significantly higher compared with that in the control group (P<0.01). Taken
      together, these results have demonstrated that CCL2 is able to promote alpha
      synuclein secretion and the apoptosis of neurons induced by alpha-synuclein, thus
      inducing proliferation of the microglia and secretion of TNF-alpha, IL-1beta and
      NO.

PMID- 30221729
TI  - Molecular mechanisms regarding potassium bromate-induced cardiac hypertrophy
      without apoptosis in H9c2 cells.
AB  - Cardiac hypertrophy is commonly involved in cardiac injury. Oxidative stress can
      induce cardiac hypertrophy with apoptosis. Potassium bromate (KBrO3) has been
      widely used as a food additive due to its oxidizing properties. In the present
      study, the rat-derived heart cell line H9c2 was used to investigate the effect of
      KBrO3 on cell size. KBrO3 increased cell size at concentrations <250 uM, in a
      dose-dependent manner. Additionally, KBrO3 also promoted the gene expression of
      two biomarkers of cardiac hypertrophy, brain/B-type natriuretic peptides (BNP)
      and beta-Myosin Heavy Chain (beta-MHC). However, apoptosis remained unobserved in
      these cells. Moreover, mediation of free radicals was investigated using a
      fluorescence assay, and it was observed that superoxide and reactive oxygen
      species (ROS) levels increased with KBrO3. Effects of KBrO3 were significantly
      reduced by tiron at concentrations sufficient to produce antioxidant-like action.
      Additionally, signals involved in cardiac hypertrophy such as calcineurin and
      nuclear factor of activated T-cells (NFAT) were also determined using western
      blot analysis. KBrO3 increased the protein levels of both these molecules which
      were decreased by tiron in a dose-dependent manner. Additionally, cyclosporine A
      attenuated the cardiac hypertrophy induced by KBrO3 in H9c2 cells at
      concentrations effective to inhibit calcineurin, in addition to reducing mRNA
      levels of BNP or beta-MHC. Finally, apoptosis was also identified in H9c2 cells
      incubated with KBrO3 at concentrations >300 uM. Collectively, these results
      provided a novel perspective that KBrO3 induces cardiac hypertrophy without
      apoptosis at a low dose through the generation of ROS, activating the
      calcineurin/NFAT signaling pathway in H9c2 cells. Therefore, at a dose <250 uM,
      KBrO3 can be applied as an inducer of cardiac hypertrophy without apoptosis in
      H9c2 cells. KBrO3 can also be developed as a tool to induce cardiac hypertrophy
      in animals.

PMID- 30221732
TI  - Inhibition of CCL19 benefits non-alcoholic fatty liver disease by inhibiting
      TLR4/NF-kappaB-p65 signaling.
AB  - Non-alcoholic fatty liver disease (NAFLD), which affects approximately one-third
      of the general population, has become a global health problem. Thus, more
      effective treatments for NAFLD are urgently required. In the present study, high
      levels of C-C motif ligand 19 (CCL19), signaling pathways such as Toll-like
      receptor 4 (TLR4)/nuclear factor-kappaB (NF-kappaB), and proinflammatory factors
      including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were
      detected in NAFLD patients, thereby indicating that there may be an association
      between CCL19 and these factors in NAFLD progression. Using a high-fat diet
      (HFD), the present study generated a Sprague-Dawley rat model of NAFLD, which
      displayed dyslipidemia with increased levels of plasma aspartate
      aminotransferase, alanine aminotransferase, total cholesterol and triglyceride.
      Dyslipidemia, liver histopathology and gene expression analyses indicated that
      the NAFLD model was successfully induced by HFD, and metformin and berberine
      (BBR) were effective treatments for NAFLD. HFD-induced CCL19 levels and
      associated factors were markedly reduced by the two drug treatments. In addition,
      metformin or BBR alone significantly promoted adenosine monophosphate-activated
      protein kinase (AMPK) phosphorylation, which was inhibited by HFD. These results
      demonstrated that metformin and BBR could improve NAFLD, which may be via the
      activation of AMPK signaling, and the high expression of CCL19 in NAFLD was
      significantly reduced by metformin and BBR. It could be inferred that inhibition
      of CCL19 may be an effective treatment for NAFLD.

PMID- 30221731
TI  - Cytoprotective effects of the medicinal herb Astragalus membranaceus on
      lipopolysaccharide-exposed cells.
AB  - Astragalus membranaceus (AM) is a traditional Chinese medicinal herb, whose
      cytoprotective effects remain largely unknown. Here, the bacterial endotoxin
      lipopolysaccharide (LPS) was applied to a human pulmonary type II-like epithelial
      lung adenocarcinoma cell line, a human umbilical vein endothelial cell line, and
      a human bladder carcinoma cell line to construct in vitro models of intracellular
      oxidative stress. The authors assayed the cellular and mitochondrial
      cytoprotective effects of varying doses of AM root extract upon these cell lines.
      The cell lines were cultured as follows: LPS-only group, four LPS+AM groups
      treated with various AM concentrations plus LPS, and an untreated control group.
      Flow cytometry was used to assess apoptosis and cell cycle progression. A 2',7'
      dichlorofluorescein-diacetate assay was used to quantitate reactive oxygen
      species (ROS) generation. Mitochondrial membrane potential (Deltapsimit) was
      analyzed by Rhodamine 123 assay. Western blotting was performed to detect cleaved
      caspase-3, p53, and B cell lymphoma (Bcl)-2 levels. Across all cell lines, LPS
      significantly elevated apoptosis rates, shifted cells to S/G2 phase, increased
      ROS production, reduced Deltapsimit, upregulated cleaved caspase-3, upregulated
      p53, and downregulated Bcl-2 relative to controls (all P<0.05). As a general
      trend, increasing AM concentrations produced progressively greater reductions in
      the apoptosis rate, greater reductions in S/G2 phase %, greater reductions in ROS
      production, greater increases in Deltapsimit, greater reductions in cleaved
      caspase-3 and p53 expression, and greater increases in Bcl-2 expression. AM
      treatment protects human pulmonary and bladder epithelial cells, in addition to
      human endothelial cells, from LPS-induced apoptosis, in a dose-dependent manner.

PMID- 30221730
TI  - Pharmacological basis for application of scutellarin in Alzheimer's disease:
      Antioxidation and antiapoptosis.
AB  - Scutellarin (SC), mainly extracted from the Chinese herb Erigeron breviscapus
      (vant.), has been reported to possess various pharmacological activities;
      however, its effects on Alzheimer's disease (AD) have not been systemically
      reported. The protective effects of SC on AD were investigated using an L
      glutamic acid (L-Glu)-damaged HT22 cell apoptosis model and an aluminum chloride
      plus D-galactose-induced AD mouse model. In L-Glu-damaged HT22 cells, SC
      significantly increased cell viability, inhibited lactate dehydrogenase release,
      reduced caspase-3 activity and suppressed apoptosis, which were determined via an
      MTT assay, an in vitro Toxicology Assay kit, a Caspase-3 activity assay kit, and
      propidium iodide and Annexin V staining. Furthermore, SC suppressed the
      accumulation of intracellular reactive oxygen species (ROS), restored the
      dissipation of mitochondrial membrane potential, enhanced the expression of
      antiapoptotic proteins and reduced the expression of pro-apoptotic proteins, as
      determined by immunofluorescence assays and western blotting. In AD mice, SC
      enhanced vertical and horizontal movements in an autonomic activity test, and
      reduced the escape latency time in the water maze test. SC reduced the deposition
      of amyloid beta1-42 (Abeta1-42) and the expression of phosphorylated-Tau in the
      hippocampus as determined by immunohistochemistry analysis, but enhanced the
      serum levels of Abeta1-42 of AD mice as determined by ELISA. ELISA analyses also
      revealed that SC enhanced the levels of acetylcholine, and superoxide dismutase
      in serum and brain lysate, whereas reduced the levels of ROS in brain lysate of
      AD mice. The present study confirmed that the protective effects of SC in AD in
      vitro and in vivo are associated with its antioxidant and antiapoptotic
      properties.

PMID- 30221728
TI  - Combination of pristimerin and paclitaxel additively induces autophagy in human
      breast cancer cells via ERK1/2 regulation.
AB  - Pristimerin, a quinonemethide triterpenoid, has demonstrated anticancer activity
      against a number of types of cancer, including breast cancer. However, its
      mechanism of action remains unclear. The present study investigated the autophagy
      induced anticancer efficacy of pristimerin on MDA-MB-231 human breast cancer
      cells. Pristimerin inhibited the growth of these cells in a concentration
      dependent manner. Treatment with pristimerin dose-dependently induced an increase
      of light chain 3B (LC3-II), whereas autophagy inhibitor 3-methyladenine (3-MA)
      inhibited pristimerin-induced LC3-II accumulation and cytotoxic effects.
      Autophagy was also activated by paclitaxel as observed by an elevated LC3-II
      level. Although 24 uM paclitaxel induced autophagy without cytotoxicity, combined
      with pristimerin it additively induced cell growth inhibition and autophagy
      induction. Autophagy induction was measured with an autophagy detection kit and
      LC3-II levels were monitored by western blot analysis. Treatment with 3-MA
      inhibited LC3-II accumulation and cell death induced by a combination of
      paclitaxel and pristimerin. Pristimerin and paclitaxel inhibited extracellular
      signal-regulated kinase (ERK)1/2/p90RSK signaling, consistent with autophagy
      indicators, namely p62 degradation and beclin 1 expression. In addition, ERK
      activator ceramide C6 treatment suppressed the LC3-II levels induced by a
      combination of paclitaxel and pristimerin. These results suggested that exposure
      to pristimerin induced autophagic cell death, whereas a combination treatment of
      pristimerin and paclitaxel resulted in an additive effect on ERK-dependent
      autophagic cell death.

PMID- 30221734
TI  - Dicer affects cisplatin-mediated apoptosis in epithelial ovarian cancer cells.
AB  - Dicer is an essential enzyme that processes micro (mi)-RNA precursors into mature
      miRNAs, and serves a critical role in cancer development and progression by
      regulating gene expression. However, the role of Dicer in cisplatin-mediated
      apoptosis and chemotherapy resistance in epithelial ovarian cancer (EOC) cells is
      poorly understood. In the present study, Dicer was expressed at low levels in
      cisplatin-resistant A2780 cells when compared with parental cells. In addition,
      knocking down Dicer using short hairpin RNA decreased the sensitivity of A2780
      and CAOV3 cells to cisplatin. Furthermore, downregulating Dicer significantly
      inhibited cisplatin-induced apoptosis in ovarian cancer cells, and decreased the
      levels of proteins involved in apoptosis signaling pathways, including P73, P63,
      P53, caspase-9 and caspase-3. These findings indicated that Dicer may be a
      promising target for overcoming drug resistance in ovarian cancer.

PMID- 30221733
TI  - Deletion of poly(ADP-ribose) polymerase-1 changes the composition of the
      microbiome in the gut.
AB  - Poly(adenosine diphosphate-ribose) polymerase (PARP)-1 is the prototypical PARP
      enzyme well known for its role in DNA repair and as a pro-inflammatory protein.
      Since PARP1 is an important co-factor of several other pro-inflammatory proteins,
      in the present study the possible changes in microbial flora of PARP1 knockout
      mice were investigated. Samples from the duodenum, cecum and feces from wild type
      and PARP1 knockout C57BL/6J male mice were collected and 16S ribosomal RNA genes
      were sequenced. Based on the sequencing results, the microbiome and compared
      samples throughout the lower part of the gastrointestinal system were
      reconstructed. The present results demonstrated that the lack of PARP1 enzyme
      only disturbed the microbial flora of the duodenum, where the biodiversity
      increased in the knockout animals on the species level but decreased on the order
      level. The most prominent change was the overwhelming abundance of the family
      Porphyromonadaceae in the duodenum of PARP1-/- animals, which disappeared in the
      cecum and feces where families were spread out more evenly than in the wild type
      animals. The findings of the present study may improve current understanding of
      the role of PARP1 in chronic inflammatory diseases.

PMID- 30221735
TI  - Two Paired Box 6 mutations identified in Chinese patients with classic congenital
      aniridia and cataract.
AB  - Congenital aniridia is a rare genetic disorder characterized by a variable degree
      of hypoplasia or absence of iris. It is frequently associated with keratopathy,
      cataract, juvenile-onset glaucoma and foveal and optic nerve hypoplasia.
      Mutations in the Paired Box 6 (PAX6) gene on chromosome 11p13 have been
      demonstrated to cause aniridia. The aim of the present study was to investigate
      the genetic variations of PAX6 in two sporadic patients from southern China with
      classic congenital aniridia and cataract. Complete ophthalmic and physical
      examinations were performed, including best-corrected visual acuity, intraocular
      pressure, slit-lamp examination, fundus examination, optical coherence
      tomography, ultrasound biomicroscopy, and Pentacam scanning. Genomic DNA was
      extracted from leukocytes of peripheral blood collected from the two patients,
      their unaffected parents and 200 unrelated control subjects from the same
      population. Exons 4-13 of the PAX6 gene were amplified by polymerase chain
      reaction and sequenced directly. Patient 1 was affected with aniridia accompanied
      by congenital cataract and nystagmus. A novel heterozygous PAX6 frameshift
      mutation c.277delG (p.Glu93SerfsX31) in exon 6 was identified in this patient.
      Patient 2 was presented with aniridia, congenital cataract, lens subluxation and
      glaucoma. A recurrent nonsense mutation c.718C>T (p.Arg240X) in exon 9 was
      identified in this patient. The present results expand the mutation spectrum of
      PAX6 and will be valuable for genetic counseling in the affected families.
      Additionally, the identification of these mutations reiterates the importance of
      PAX6 in ocular development and sheds light on the pathogenesis of congenital
      aniridia.

PMID- 30221736
TI  - Immunization with lentiviral vector-modified dendritic cells encoding
      ubiquitinated hepatitis B core antigen promotes Th1 differentiation and antiviral
      immunity by enhancing p38 MAPK and JNK activation in HBV transgenic mice.
AB  - Hepatitis B virus (HBV) infection is a global public health problem. T helper
      (Th)1-associated cytokines are involved in HBV clearance during acute and
      persistent infection. In our previous study, it was demonstrated that lentiviral
      vectors encoding ubiquitinated hepatitis B core antigen (LV-Ub-HBcAg) effectively
      transduced dendritic cells (DCs) to induce maturation, which promoted T cell
      polarization to Th1 and generated HBcAg-specific cytotoxic T lymphocytes (CTLs)
      ex vivo. In the present study, HBV transgenic mice were immunized with LV-Ub
      HBcAg-transduced DCs and HBcAg-specific immune responses were evaluated. Cytokine
      expression was analyzed by ELISA. T lymphocyte proliferation was detected with a
      Cell Counting Kit-8 assay and HBcAg-specific CTL activity was determined using a
      lactate dehydrogenase release assay. The expression levels of p38-mitogen
      activated protein kinase (p38-MAPK), phosphorylated (p)-p38MAPK, c-Jun N-terminal
      kinase (JNK) and p-JNK were detected by western blot analysis. The results
      demonstrated that LV-Ub-HBcAg-transduced DCs significantly increased the Th1/Th2
      cytokine ratio, and effectively reduced the levels of serum hepatitis B surface
      antigen (HBsAg), HBV DNA, and liver HBsAg and HBcAg. Furthermore, the LV-Ub-HBcAg
      transduced DCs upregulated the expression of p-P38-MAPK and p-JNK in T
      lymphocytes. In conclusion, the present study indicated that LV-Ub-HBcAg
      transduced DCs generated predominant Th1 responses and enhanced CTL activity in
      HBV transgenic mice. Activation of the P38-MAPK/JNK signaling pathway may be
      involved in this induction.

PMID- 30221737
TI  - Aldehyde dehydrogenase activity in cryopreserved cord blood cells for quality
      assessment prior to transplantation.
AB  - In umbilical cord blood transplantation (UCBT), the number of cluster of
      differentiation (CD)34+ cells and colony-forming units (CFUs) in the cord blood
      (CB) graft positively correlate with patient survival. Therefore, these
      parameters are currently used for quality assessment of the cryopreserved CB
      cells in the attached segment that is considered representative of the CB in the
      main bag prior to UCBT. Since aldehyde dehydrogenase (ALDH) activity is high in
      hematopoietic stem cells, the number of ALDH-bright (ALDHbr) cells was examined
      in comparison with the number of CD34+ cells and CFUs for the quality assessment
      of CB units. In the cryopreserved main bag, the number of ALDHbr cells in the CB
      unit exhibited positive correlation with the number of CD34+ cells, and with CFU
      granulocytes/macrophages and total CFU counts. Furthermore, the concentration of
      ALDHbr cells in the cryopreserved attached segment was not significantly
      different compared to that of the main bag, suggesting that the attached segment
      is representative of the main bag. In conclusion, the present study suggested
      that ALDHbr cell counts in the cryopreserved attached segments may serve as a
      quality assessment indicator for CB units prior to UCBT.

PMID- 30221738
TI  - Modular bioinformatics analysis demonstrates that a Toll-like receptor signaling
      pathway is involved in the regulation of macrophage polarization.
AB  - In recent years, an increasing number of studies on the roles of macrophages in
      tumors, immune responses and metabolism have been published, in which macrophage
      polarization has been an extensively discussed topic. In the present study,
      differentially expressed genes in various types of macrophages were analyzed
      using the Gene Expression Omnibus database. Cluster analysis of differentially
      expressed genes was conducted, and a protein-protein interaction (PPI) network
      was constructed. Finally, modular analysis and functional enrichment analysis
      revealed that a Toll-like receptor (TLR) signaling pathway is involved in the
      regulation of macrophage polarization. Furthermore, the high-degree proteins in
      the PPI network that are involved in the molecular regulation of macrophage
      polarization are closely associated with proteins of the TLR signaling pathway.
      These results suggested that the TLR signaling pathways may be a principal
      direction of future research on the regulation of macrophage polarization.

PMID- 30221740
TI  - Complement depletion with cobra venom factor alleviates acute hepatic injury
      induced by ischemia-reperfusion.
AB  - Increasing evidence has demonstrated that complement activation is required for
      ischemia-reperfusion injury (IRI)-induced hepatic damage, and cobra venom factor
      (CVF) can deplete the complement components. The aim of the current study was to
      investigate the effect and intrinsic mechanism of CVF pretreatment on IRI-induced
      acute hepatic injury in rats. Acute hepatic injury in rats was induced by bone
      fracture to simulate trauma, followed by hemorrhage for 90 min, and then the rats
      were resuscitated for a period of 20 min of reperfusion. The survival times under
      different CVF treatment doses and schedules for rats with IRI were evaluated.
      Hepatic tissues and serum samples were analyzed for acute hepatic injury,
      complement activation, inflammatory mediator release and apoptosis at
      predetermined times and compared between the IRI group and the CVF pretreatment +
      IRI groups. Compared to the rats with IRI alone, the survival times were
      significantly improved among rats with IRI receiving a high-dose or low-dose CVF
      pretreatment (all P<0.01). Upon histological examination, severe hepatic damage
      was observed in the rats with IRI, accompanied by liver function deterioration,
      complement and membrane attack complex activation, inflammatory mediator release
      and hepatic cell apoptosis. CVF pretreatment significantly attenuated the hepatic
      injury through depletion of anaphylatoxic C5a and membrane attack complex C5b-9
      activation, and subsequent inhibition of inflammatory mediator release and
      hepatic cell apoptosis (all P<0.05). The results indicated that CVF pretreatment
      ameliorates IRI-induced acute hepatic injury. However, further studies are
      required to determine whether this therapy could be a potential agent for the
      treatment of IRI injuries in clinical settings.

PMID- 30221741
TI  - Application of medical adhesive inhibits intimal hyperplasia involving the
      downregulation of ERK1/2 and eNOS levels.
AB  - Vein graft remains the most broadly applied vascular material in coronary artery
      bypass surgery. However, the restenosis rate of the vein bridge following
      angioplasty is high. The present study investigated the effect of medical
      adhesive on vascular intimal hyperplasia, in addition to the signal transduction
      mechanism. A total of 36 New Zealand white rabbits were divided into three groups
      at random, including the normal group, the surgery group and the medical adhesive
      spray group. Following surgery for transplantation of the left external jugular
      vein to the ipsilateral common carotid artery for 4 weeks, the thickness and area
      of the intima and media of the vessel were measured on formalin-fixed, paraffin
      wax-embedded pathological sections using hematoxylin-eosin staining, and
      alterations in the expression of proliferating cell nuclear antigen (PCNA),
      platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion
      protein 1 (VCAM-1), extracellular signal-regulated kinase (ERK)1/2, and
      endothelial nitric oxide synthase (eNOS) were detected by immunohistochemical
      staining, reverse transcription-quantitative polymerase chain reaction analysis
      and western blotting. The levels of intimal hyperplasia in the medical adhesive
      spray group were markedly decreased compared with the surgery group.
      Consistently, PCNA, PECAM-1 and VCAM-1 were underexpressed in the medical
      adhesive spray group compared with the surgery group. ERK1/2 and eNOS were
      underexpressed in the medical adhesive spray group compared with the surgery
      group. Therefore, the application of medical adhesive may inhibit intimal
      hyperplasia, which may be associated with the restriction of the over-distension
      of the vein graft by downregulating the ERK1/2 and eNOS levels, reducing injury
      to the vascular intima and inhibiting the signaling pathway involved in intimal
      hyperplasia.

PMID- 30221739
TI  - Distribution and prognostic value of tumor-infiltrating T cells in breast cancer.
AB  - Tumor-infiltrating lymphocytes are associated with the response to neoadjuvent
      chemotherapy and prognosis in breast cancer. However, the distribution,
      interaction and prognostic value of tumor-infiltrating T cells, the main
      component of the tumor microenvironment, have seldom been reported. In the
      present study, surgical specimens of 72 breast cancer patients were analyzed.
      Tumor-infiltrating T cell subsets [cluster of differentiation (CD)4+T, CD8+T and
      regulatory T cells] and expression of their cytokines [interferon-gamma,
      interleukin (IL)-4, and IL-17] were evaluated by flow cytometry. These parameters
      together with The Cancer Genome Atlas database were used to demonstrate the
      distribution, interaction and prognostic value of tumor-infiltrating T cells in
      breast cancer. Tumor-infiltrating lymphocytes were closely associated with
      histological grade (P=0.03), estrogen receptor status (P=0.006), human epidermal
      growth factor receptor 2 status (P=0.047) and molecular subtype in breast cancer
      (P=0.012). The gene expression of CD4, CD8A and forkhead box protein P3 in the
      tumor was increased compared with healthy breast tissue, and was positively
      associated with the prognosis of breast cancer patients. HER2+ and triple
      negative breast cancer exhibited a significantly increased percentage of CD4+T
      cells (P=0.01) and regulatory T cells (P=0.035), and a decreased percentage of
      CD8+T cells (P=0.006) compared with the luminal subtype. Furthermore, the
      regulatory T cell number was positively correlated with CD8+T cell number in
      tumors (R=0.7, P=1.5x10-162) and significantly inhibited the cytokine secretion
      of T cells. These results reveal the distribution and interaction of tumor
      infiltrating T cell subsets, and indicate that CD8+T cells and regulatory T cells
      may be used as reliable predictors of prognosis in breast cancer.

PMID- 30221597
TI  - Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.
AB  - BACKGROUND: Aspirin is a well-established therapy for the secondary prevention of
      cardiovascular events. However, its role in the primary prevention of
      cardiovascular disease is unclear, especially in older persons, who have an
      increased risk. METHODS: From 2010 through 2014, we enrolled community-dwelling
      men and women in Australia and the United States who were 70 years of age or
      older (or >=65 years of age among blacks and Hispanics in the United States) and
      did not have cardiovascular disease, dementia, or disability. Participants were
      randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The
      primary end point was a composite of death, dementia, or persistent physical
      disability; results for this end point are reported in another article in the
      Journal. Secondary end points included major hemorrhage and cardiovascular
      disease (defined as fatal coronary heart disease, nonfatal myocardial infarction,
      fatal or nonfatal stroke, or hospitalization for heart failure). RESULTS: Of the
      19,114 persons who were enrolled in the trial, 9525 were assigned to receive
      aspirin and 9589 to receive placebo. After a median of 4.7 years of follow-up,
      the rate of cardiovascular disease was 10.7 events per 1000 person-years in the
      aspirin group and 11.3 events per 1000 person-years in the placebo group (hazard
      ratio, 0.95; 95% confidence interval [CI], 0.83 to 1.08). The rate of major
      hemorrhage was 8.6 events per 1000 person-years and 6.2 events per 1000 person
      years, respectively (hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001).
      CONCLUSIONS: The use of low-dose aspirin as a primary prevention strategy in
      older adults resulted in a significantly higher risk of major hemorrhage and did
      not result in a significantly lower risk of cardiovascular disease than placebo.
      (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov
      number, NCT01038583 .).

PMID- 30221742
TI  - Novel SIRT1 inhibitor 15-deoxy-Delta12,14-prostaglandin J2 and its derivatives
      exhibit anticancer activity through apoptotic or autophagic cell death pathways
      in SKOV3 cells.
AB  - Clinically relevant sirtuin (SIRT) inhibitors may possess antitumor activities. A
      previous study indicated that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2)
      exhibited potent anticancer activity by SIRT1 inhibition. Therefore, the aim of
      the present study was to investigate whether its derivatives (J11-C1 and J19)
      exhibited anticancer activity against ovarian cancer SKOV3 cells. Cell viability
      was determined using an MTT assay. Cell cycle arrest, apoptosis and autophagy
      were determined using flow cytometry or western blot analysis. J11-Cl and J19
      were less cytotoxic to SKOV3 cells compared with 15d-PGJ2. Molecular docking
      studies supported the interactions of 15d-PGJ2, J11-Cl and J19 with various amino
      acids in SIRT1 proteins. Similar to 15d-PGJ2, J11-C1 and J19 inhibited SIRT1
      enzymatic activity and decreased SIRT1 expression levels in a concentration
      dependent manner. J11-C1 induced apoptotic cell death more effectively compared
      with J19, which was associated with markedly decreased expression of the anti
      apoptotic molecule B-cell lymphoma 2 (Bcl-2). Furthermore, the levels of light
      chain 3-II (LC3-II) and beclin-1 were clearly induced in SKOV3 cells treated with
      J11-Cl. Thus, 15d-PGJ2 and its derivatives exhibited anticancer activity possibly
      by inducing apoptotic or autophagic cell death pathways. Collectively, the
      results of the present study suggest that 15d-PGJ2 and its derivatives exerted
      antitumor activity by selectively modulating the expression of genes associated
      with cell cycle arrest, apoptosis and autophagy. Notably, J11-C1 is a novel
      candidate SIRT1 inhibitor with anticancer activity.

PMID- 30221743
TI  - Identification of key genes and associated pathways in KIT/PDGFRA wild-type
      gastrointestinal stromal tumors through bioinformatics analysis.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal
      tumor in the gastrointestinal tract. The present study aimed to identify the
      potential candidate biomarkers that may be involved in the pathogenesis and
      progression of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
      (KIT)/platelet-derived growth factor receptor alpha (PDGFRA) wild-type GISTs. A
      joint bioinformatics analysis was performed to identify the differentially
      expressed genes (DEGs) in wild-type GIST samples compared with KIT/PDGFRA mutant
      GIST samples. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathway enrichment analysis of DEGs was conducted using Database for
      Annotation, Visualization and Integrated Discovery and KEGG Orthology-Based
      Annotation System (KOBAS) online tools, respectively. Protein-protein interaction
      (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval
      of Interacting Genes online tool and Cytoscape, and divided into sub-networks
      using the Molecular Complex Detection (MCODE) plug-in. Furthermore, enrichment
      analysis of DEGs in the modules was analyzed with KOBAS. In total, 546 DEGs were
      identified, including 238 upregulated genes primarily enriched in 'cell
      adhesion', 'biological adhesion', 'cell-cell signaling', 'PI3K-Akt signaling
      pathway' and 'ECM-receptor interaction', while the 308 downregulated genes were
      predominantly involved in 'inflammatory response', 'sterol metabolic process' and
      'fatty acid metabolic process', 'small GTPase mediated signal transduction',
      'cAMP signaling pathway' and 'proteoglycans in cancer'. A total of 25 hub genes
      were obtained and four modules were mined from the PPI network, and sub-networks
      also revealed these genes were primarily involved in significant pathways,
      including 'PI3K-Akt signaling pathway', 'proteoglycans in cancer', 'pathways in
      cancer', 'Rap1 signaling pathway', 'ECM-receptor interaction', 'phospholipase D
      signaling pathway', 'ras signaling pathway' and 'cGMP-PKG signaling pathway'.
      These results suggested that several key hub DEGs may serve as potential
      candidate biomarkers for wild-type GISTs, including phosphatidylinositol-4,5
      bisphosphate 3-kinase, catalytic subunit gamma, insulin like growth factor 1
      receptor, hepatocyte growth factor, thrombospondin 1, Erb-B2 receptor tyrosine
      kinase 2 and matrix metallopeptidase 2. However, further experiments are required
      to confirm these results.

PMID- 30221744
TI  - Sarcomatoid carcinoma of the pancreas: A case report and review of the
      literature.
AB  - Sarcomatoid carcinoma (SC) is an extremely rare and complicated malignant
      neoplasm that consists of both malignant epithelial components and atypical
      spindle cells that express an epithelial phenotype. The presents study reported a
      case of SC of the pancreas (SCP), along with a brief review of the literature. A
      63-year-old man was admitted to The Second Hospital of Jilin University hospital
      with complaints of epigastralgia and jaundice of one month in duration. Based on
      preoperative laboratory blood tests and radiography, a mass at the distal common
      bile duct was suspected. Intraoperative examination discovered a 2.5x2x1.8-cm
      mass in the pancreatic head, with invasion of the distal bile duct.
      Pancreaticoduodectomy was performed. Histopathology and immunohistochemistry of
      the specimen confirmed the diagnosis of SCP. The patient succumbed 18 months
      after surgery due to multiple hepatic metastases.

PMID- 30221748
TI  - Continuing the Effort to Predict Risk of Future Unplanned Healthcare Use in Older
      Adults.

PMID- 30221745
TI  - Bronchoscopy-guided antimicrobial therapy for cystic fibrosis.
AB  - BACKGROUND: Early diagnosis and treatment of lower respiratory tract infections
      are the mainstay of management of lung disease in cystic fibrosis. When sputum
      samples are unavailable, treatment relies mainly on cultures from oropharyngeal
      specimens; however, there are concerns regarding the sensitivity of these to
      identify lower respiratory organisms.Bronchoscopy and related procedures
      (including bronchoalveolar lavage) though invasive, allow the collection of lower
      respiratory specimens from non-sputum producers. Cultures of bronchoscopic
      specimens provide a higher yield of organisms compared to those from
      oropharyngeal specimens. Regular use of bronchoscopy and related procedures may
      help in a more accurate diagnosis of lower respiratory tract infections and guide
      the selection of antimicrobials, which may lead to clinical benefits.This is an
      update of a previous review. OBJECTIVES: To evaluate the use of bronchoscopy
      guided antimicrobial therapy in the management of lung infection in adults and
      children with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic
      Fibrosis Trials Register, compiled from electronic database searches and
      handsearching of journals and conference abstract books. Date of latest search:
      30 August 2018.We also searched three registries of ongoing studies and the
      reference lists of relevant articles and reviews. Date of latest search: 10 April
      2018. SELECTION CRITERIA: We included randomized controlled studies including
      people of any age with cystic fibrosis, comparing outcomes following therapies
      guided by the results of bronchoscopy (and related procedures) with outcomes
      following therapies guided by the results of any other type of sampling
      (including cultures from sputum, throat swab and cough swab). DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected studies, assessed their risk
      of bias and extracted data. We contacted study investigators for further
      information. The quality of the evidence was assessed using the GRADE criteria.
      MAIN RESULTS: The search identified 11 studies, but we only included one study
      enrolling infants with cystic fibrosis under six months of age and diagnosed
      through newborn screening (170 enrolled); participants were followed until they
      were five years old (data from 157 children). The study compared outcomes
      following therapy directed by bronchoalveolar lavage for pulmonary exacerbations
      with standard treatment based on clinical features and oropharyngeal cultures.We
      considered this study to have a low risk of bias; however, the statistical power
      to detect a significant difference in the prevalence of Pseudomonas aeruginosa
      was limited due to the prevalence (of Pseudomonas aeruginosa isolation in
      bronchoalveolar lavage samples at five years age) being much lower in both the
      groups compared to that which was expected and which was used for the power
      calculation. The sample size was adequate to detect a difference in high
      resolution computed tomography scoring. The quality of evidence for the key
      parameters was graded as low except high-resolution computed tomography scoring
      and cost of care analysis, which were graded as moderate quality.At five years of
      age, there was no clear benefit of bronchoalveolar lavage-directed therapy on
      lung function z scores or nutritional parameters. Evaluation of total and
      component high-resolution computed tomography scores showed no significant
      difference in evidence of structural lung disease in the two groups.In addition,
      this study did not show any difference between the number of isolates of
      Pseudomonas aeruginosa per child per year diagnosed in the bronchoalveolar lavage
      directed therapy group compared to the standard therapy group. The eradication
      rate following one or two courses of eradication treatment was comparable in the
      two groups, as were the number of pulmonary exacerbations. However, the number of
      hospitalizations was significantly higher in the bronchoalveolar lavage-directed
      therapy group, but the mean duration of hospitalizations was significantly less
      compared to the standard therapy group.Mild adverse events were reported in a
      proportion of participants, but these were generally well-tolerated. The most
      common adverse event reported was transient worsening of cough after 29% of
      procedures. Significant clinical deterioration was documented during or within 24
      hours of bronchoalveolar lavage in 4.8% of procedures. AUTHORS' CONCLUSIONS: This
      review, limited to a single, well-designed randomized controlled study, shows no
      clear evidence to support the routine use of bronchoalveolar lavage for the
      diagnosis and management of pulmonary infection in pre-school children with
      cystic fibrosis compared to the standard practice of providing treatment based on
      results of oropharyngeal culture and clinical symptoms. No evidence was available
      for adult and adolescent populations.

PMID- 30221746
TI  - Outpatient Antibiotic Prescribing for Older Adults in the United States: 2011 to
      2014.
AB  - OBJECTIVES: To characterize antibiotics prescribed to older adults to guide
      efforts to improve antibiotic use. DESIGN: Descriptive analysis. SETTING:
      Ambulatory. PARTICIPANTS: Adults aged 65 and older in the United States.
      MEASUREMENTS: Information on outpatient antibiotic prescriptions dispensed for
      older adults from 2011 to 2014 was extracted from the IQVIA Xponent database. A
      chi-square trend analysis was conducted to assess annual changes in antibiotic
      prescribing rates. A descriptive analysis of prescribing rates by antibiotic, age
      group, sex, state, Census region, and provider specialty was conducted. RESULTS:
      From 2011 to 2014, outpatient antibiotic prescribing rates remained stable in
      older U.S. adults (P = .89). In 2014, older adults were dispensed 51.6 million
      prescriptions (1,115 prescriptions/1,000 persons). Persons aged 75 and older had
      a higher prescribing rate (1,157 prescriptions/1,000 persons) than those aged 65
      to 74 (1,084 prescriptions/1,000 persons). Prescribing rates were highest in the
      South 1228 prescriptions/1,000 persons) and lowest in the West (854
      prescriptions/1,000 persons). The most commonly prescribed class was quinolones,
      followed by penicillins and macrolides. Azithromycin was the most commonly
      prescribed drug, followed by amoxicillin and ciprofloxacin. Internists and family
      physicians prescribed 43% of antibiotic courses. CONCLUSION: On average, in 2014,
      U.S. adults aged 65 and older received enough outpatient antibiotic courses for
      every older adult to receive at least 1. Quinolones and azithromycin are
      potential targets for assessing the appropriateness of antibiotic prescribing in
      this population. Interventions to improve use targeting internists and family
      physicians in the South Census region might have the potential to have the
      greatest effect.

PMID- 30221747
TI  - Cumulative Antidepressant Use and Risk of Dementia in a Prospective Cohort Study.
AB  - OBJECTIVES: To determine whether antidepressant use is associated with dementia
      risk. DESIGN: Prospective cohort study. SETTING: Kaiser Permanente Washington
      (KPWA), an integrated healthcare delivery system. PARTICIPANTS: Community
      dwelling individuals aged 65 and older without dementia and with 10 years or more
      of KPWA enrollment at baseline (N=3,059). MEASUREMENTS: Primary exposures were
      selective serotonin reuptake inhibitors (paroxetine vs other), tricyclic
      antidepressants, and serotonin antagonist and reuptake inhibitors. Using health
      plan pharmacy data, we calculated cumulative medication exposure, defined as
      total standardized daily doses (TSDDs), over rolling 10-year windows. Exposure in
      the most recent year was excluded to avoid use related to prodromal symptoms. The
      Cognitive Abilities Screening Instrument was administered every 2 years; low
      scores triggered clinical evaluation and consensus diagnosis procedures. Dementia
      risk was estimated according to medication use using Cox proportional hazards
      models. RESULTS: During a mean follow-up of 7.7 years, 775 participants (25%)
      developed dementia; 659 (22%) developed possible or probable Alzheimer's disease.
      Individual antidepressant classes were not associated with differences in
      dementia risk, although paroxetine use was associated with higher risk of
      dementia for all TSDD categories than no use (0-90 TSDDs: hazard ratio (HR)=1.69,
      95% confidence interval (CI)=1.18-2.42; 91-365 TSDDs: HR=1.40, 95% CI=0.88-2.23;
      366-1095 TSDDs: HR=2.13, 95% CI=1.32-3.43; >=1095 TSDDs: HR=1.42, 95% CI=0.82
      2.46). CONCLUSION: Most commonly prescribed nonanticholinergic depression
      medications used in late life do not appear to be associated with dementia risk.
      Paroxetine and other anticholinergic antidepressants may be exceptions in older
      individuals. Future studies are warranted to improve scientific understanding of
      potential associations in other settings and populations.

PMID- 30221750
TI  - Genomic African and Native American Ancestry and 15-Year Cognitive Trajectory:
      Bambui Study, Brazil.
AB  - OBJECTIVES: To investigate the association between African and Native American
      genomic ancestry and long-term cognitive trajectories in admixed Brazilians.
      DESIGN: Population-based longitudinal study. SETTING: Bambui-Epigen (Brazil)
      cohort study. PARTICIPANTS: Adults aged 60 and older (N=1,215) MEASUREMENTS:
      Participants were followed from January 1997 to December 2011. Cognitive function
      was assessed annually using the Mini-Mental State Examination (MMSE), totaling
      12,208 measurements. We used linear mixed-effects pattern models to assess MMSE
      score trajectories. Ancestry was assessed using a genome-wide approach. RESULTS:
      After adjustments for covariates, the highest quintile of African ancestry was
      associated with poorer baseline cognitive performance (beta=-0.73, 95% confidence
      interval (CI)=-1.36 to -0.11) but not with cognitive trajectory. Educational
      level modified the baseline association between highest African ancestry and
      cognitive performance in that the association was observed only in those with
      very low (<4 years) education (beta=-1.13, 95% CI=-2.02 to -0.23). No association
      was found between Native American ancestry and baseline cognitive function or its
      trajectory. CONCLUSION: Genomic African and Native American ancestry levels had
      no prognostic value for age-related cognitive decline in this admixed population.

PMID- 30221749
TI  - Prophylactic platelet transfusions prior to surgery for people with a low
      platelet count.
AB  - BACKGROUND: People with thrombocytopenia often require a surgical procedure. A
      low platelet count is a relative contraindication to surgery due to the risk of
      bleeding. Platelet transfusions are used in clinical practice to prevent and
      treat bleeding in people with thrombocytopenia. Current practice in many
      countries is to correct thrombocytopenia with platelet transfusions prior to
      surgery. Alternatives to platelet transfusion are also used prior surgery.
      OBJECTIVES: To determine the clinical effectiveness and safety of prophylactic
      platelet transfusions prior to surgery for people with a low platelet count.
      SEARCH METHODS: We searched the following major data bases: Cochrane Central
      Register of Controlled Trials (CENTRAL; 2017, Issue 2), PubMed (e-publications
      only), Ovid MEDLINE, Ovid Embase, the Transfusion Evidence Library and ongoing
      trial databases to 11 December 2017. SELECTION CRITERIA: We included all
      randomised controlled trials (RCTs), as well as non-RCTs and controlled before
      and-after studies (CBAs), that met Cochrane EPOC (Effective Practice and
      Organisation of Care) criteria, that involved the transfusion of platelets prior
      to surgery (any dose, at any time, single or multiple) in people with low
      platelet counts. We excluded studies on people with a low platelet count who were
      actively bleeding. DATA COLLECTION AND ANALYSIS: We used standard methodological
      procedures expected by Cochrane for data collection. We were only able to combine
      data for two outcomes and we presented the rest of the findings in a narrative
      form. MAIN RESULTS: We identified five RCTs, all conducted in adults; there were
      no eligible non-randomised studies. Three completed trials enrolled 180 adults
      and two ongoing trials aim to include 627 participants. The completed trials were
      conducted between 2005 and 2009. The two ongoing trials are scheduled to complete
      recruitment by October 2019. One trial compared prophylactic platelet
      transfusions to no transfusion in people with thrombocytopenia in an intensive
      care unit (ICU). Two small trials, 108 participants, compared prophylactic
      platelet transfusions to other alternative treatments in people with liver
      disease. One trial compared desmopressin to fresh frozen plasma or one unit of
      platelet transfusion or both prior to surgery. The second trial compared platelet
      transfusion prior to surgery with two types of thrombopoietin mimetics:
      romiplostim and eltrombopag. None of the included trials were free from
      methodological bias. No included trials compared different platelet count
      thresholds for administering a prophylactic platelet transfusion prior to
      surgery. None of the included trials reported on all the review outcomes and the
      overall quality per reported outcome was very low.None of the three completed
      trials reported: all-cause mortality at 90 days post surgery; mortality secondary
      to bleeding, thromboembolism or infection; number of red cell or platelet
      transfusions per participant; length of hospital stay; or quality of life.None of
      the trials included children or people who needed major surgery or emergency
      surgical procedures.Platelet transfusion versus no platelet transfusion (1 trial,
      72 participants)We were very uncertain whether giving a platelet transfusion
      prior to surgery had any effect on all-cause mortality within 30 days (1 trial,
      72 participants; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.41 to 1.45;
      very-low quality evidence). We were very uncertain whether giving a platelet
      transfusion prior to surgery had any effect on the risk of major (1 trial, 64
      participants; RR 1.60, 95% CI 0.29 to 8.92; very low-quality evidence), or minor
      bleeding (1 trial, 64 participants; RR 1.29, 95% CI 0.90 to 1.85; very-low
      quality evidence). No serious adverse events occurred in either study arm (1
      trial, 72 participants, very low-quality evidence).Platelet transfusion versus
      alternative to platelet transfusion (2 trials, 108 participants)We were very
      uncertain whether giving a platelet transfusion prior to surgery compared to an
      alternative has any effect on the risk of major (2 trials, 108 participants; no
      events; very low-quality evidence), or minor bleeding (desmopressin: 1 trial, 36
      participants; RR 0.89, 95% CI 0.06 to 13.23; very-low quality evidence:
      thrombopoietin mimetics: 1 trial, 65 participants; no events; very-low quality
      evidence). We were very uncertain whether there was a difference in transfusion
      related adverse effects between the platelet transfused group and the alternative
      treatment group (desmopressin: 1 trial, 36 participants; RR 2.70, 95% CI 0.12 to
      62.17; very-low quality evidence). AUTHORS' CONCLUSIONS: Findings of this review
      were based on three small trials involving minor surgery in adults with
      thrombocytopenia. We found insufficient evidence to recommend the administration
      of preprocedure prophylactic platelet transfusions in this situation with a lack
      of evidence that transfusion resulted in a reduction in postoperative bleeding or
      all-cause mortality. The small number of trials meeting the inclusion criteria
      and the limitation in reported outcomes across the trials precluded meta-analysis
      for most outcomes. Further adequately powered trials, in people of all ages, of
      prophylactic platelet transfusions compared with no transfusion, other
      alternative treatments, and considering different platelet thresholds prior to
      planned and emergency surgical procedures are required. Future trials should
      include major surgery and report on bleeding, adverse effects, mortality (as a
      long-term outcome) after surgery, duration of hospital stay and quality of life
      measures.

PMID- 30221751
TI  - Mycophenolate mofetil in paediatric autoimmune or immune-mediated diseases of the
      central nervous system: clinical experience and recommendations.
AB  - AIM: To gather data on mycophenolate mofetil (MMF) in paediatric
      autoimmune/immune-mediated central nervous system (CNS) conditions, focusing on
      safety and factors that may affect MMF efficacy. METHOD: Retrospective,
      multicentre study based on four paediatric neurology centres. RESULTS: Forty-four
      children were included (30 females, 14 males): 19 had proven/suspected autoimmune
      encephalitis, 14 had inflammatory demyelinating CNS diseases, and 11 had other
      autoimmune/immune-mediated CNS conditions. Before MMF, all received first-line
      immune therapies, and 17 had second-line rituximab and/or cyclophosphamide. MMF
      was started at a median of 9.5 months from disease onset (range 1-127mo) (median
      age 9y 4mo, range 1y 5mo-16y 5mo), and was used for median 18 months (range 0.3
      73mo). On MMF, 31 patients were relapse-free, whereas eight relapsed (excluding
      patients with chronic-progressive course). Relapses on MMF were associated with
      medication weaning/cessation, or with suboptimal MMF dosage/duration. Adverse
      events of MMF occurred in eight patients: six moderate (gastrointestinal,
      movement disorder, dermatological) and two severe (infectious). INTERPRETATION:
      MMF use in paediatric neuroimmunology is heterogeneous, although relatively safe.
      We have identified factors that may affect MMF efficacy and provide
      recommendations on MMF usage. WHAT THIS PAPER ADDS: Mycophenolate mofetil (MMF)
      use was heterogeneous with relatively common adverse events, although mostly not
      severe. MMF treatment reduced median annualized relapse rate, although 20% of
      patients relapsed on MMF. A high relapse rate pre-MMF and late MMF start were
      associated with higher probability of relapsing on MMF. Most relapses were
      associated with suboptimal MMF dosage, short MMF duration, or concurrent
      medication weaning/discontinuation.

PMID- 30221752
TI  - The Doctor Shortage.

PMID- 30221754
TI  - Migrainous Headache Accompanied by Hemi-Atrophy of the Tongue in Carotid Artery
      Dissection.

PMID- 30221755
TI  - Nusinersen treatment of spinal muscular atrophy: current knowledge and existing
      gaps.
AB  - Spinal muscular atrophy (SMA) is a recessive disorder caused by a mutation in the
      survival motor neuron 1 gene (SMN1); it affects 1 in 11 000 newborn infants. The
      most severe and most common form, type 1 SMA, is associated with early mortality
      in most cases and severe disability in survivors. Nusinersen, an antisense
      oligonucleotide, promotes production of full-length protein from the pseudogene
      SMN2. Nusinersen treatment prolongs survival of patients with type 1 SMA and
      allows motor milestone acquisition. Patients with type 2 SMA also show progress
      on different motor scales after nusinersen treatment. Nusinersen was recently
      approved by the European Medicines Agency and the US Food and Drug
      Administration; it is now reimbursed in several European countries and in the
      USA. In Australia, the transition from expanded access programme to commercial
      availability is coming soon. In New Zealand, an expanded access programme is
      opened, and in Canada price negotiation for the treatment is in progress. In this
      review we exemplify the clinical benefit of nusinersen in subgroups of patients
      with SMA. Nusinersen represents the first efficacious marked approved drug in
      type 1 and type 2 SMA. Different knowledge gaps, such as results in older
      patients, in patients with permanent ventilation, in patients with neonatal
      forms, or in patients after spinal fusion, still need to be addressed. WHAT THIS
      PAPER ADDS: Identifies gaps in knowledge about the efficacy of nusinersen in
      broader populations of patients with spinal muscular atrophy. Identifies open
      questions in populations of patients where proof of efficacy is available.

PMID- 30221756
TI  - Emerging Adult Risky Sexual Behavior Predicted by Parental Overprotection:
      Moderated Mediation Analysis.
AB  - Parental control behaviors are suggested to be related to emerging adult
      outcomes, such as risky sexual behavior. Although parental control behaviors are
      more likely to be considered protective against risky sexual behavior, the
      relation between parental overprotection and risky sexual behavior is unclear.
      Furthermore, parental overprotection may influence peer selection and prosocial
      behaviors in emerging adults, which may in turn influence outcomes of risky
      sexual behavior, as suggested by primary socialization theory. Thus, the current
      study investigated the relations among paternal and maternal overprotection,
      emerging adult peer alienation, and risky sexual behavior, and expanded on these
      relations by examining gender effects of both parents and children. The sample
      consisted of 505 participants (228 males and 277 females) ranging in age from 18
      to 25 years. Analyses were conducted with AMOS path analysis and indicated that
      peer alienation mediated the effect between both maternal and paternal perceived
      overprotection and risky sexual behavior, but more strongly for males, suggesting
      moderated mediation. Overall, parental overprotection may be protective against
      risky sexual behavior via pathways that are harmful such as peer alienation, thus
      recommending research continues to clarify the nuances of these relations.

PMID- 30221753
TI  - High-fructose corn syrup consumption in adolescent rats causes bipolar-like
      behavioural phenotype with hyperexcitability in hippocampal CA3-CA1 synapses.
AB  - BACKGROUND AND PURPOSE: Children and adolescents are the top consumers of high
      fructose corn syrup (HFCS) sweetened beverages. Even though the cardiometabolic
      consequences of HFCS consumption in adolescents are well known, the
      neuropsychiatric consequences have yet to be determined. EXPERIMENTAL APPROACH:
      Adolescent rats were fed for a month with 11% weight/volume carbohydrate
      containing HFCS solution, which is similar to the sugar-sweetened beverages of
      human consumption. The metabolic, behavioural and electrophysiological
      characteristics of HFCS-fed rats were determined. Furthermore, the effects of
      TDZD-8, a highly specific GSK-3B inhibitor, on the HFCS-induced alterations were
      further explored. KEY RESULTS: HFCS-fed adolescent rats displayed bipolar-like
      behavioural phenotype with hyperexcitability in hippocampal CA3-CA1 synapses.
      This hyperexcitability was associated with increased presynaptic release
      probability and increased readily available pool of AMPA receptors to be
      incorporated into the postsynaptic membrane, due to decreased expression of the
      neuron-specific alpha3-subunit of Na+ /K+ -ATPase and an increased ser845 
      phosphorylation of GluA1 subunits (AMPA receptor subunit) respectively. TDZD-8
      treatment was found to restore behavioural and electrophysiological disturbances
      associated with HFCS consumption by inhibition of GSK-3B, the most probable
      mechanism of action of lithium for its mood-stabilizing effects. CONCLUSION AND
      IMPLICATIONS: This study shows that HFCS consumption in adolescent rats led to a
      bipolar-like behavioural phenotype with neuronal hyperexcitability, which is
      known to be one of the earliest endophenotypic manifestations of bipolar
      disorder. Inhibition of GSK-3B with TDZD-8 attenuated hyperexcitability and
      restored HFCS-induced behavioural alterations.

PMID- 30221758
TI  - Is independence the same as participation for young people with disabilities?

PMID- 30221757
TI  - A Statewide Elder Mistreatment Virtual Assessment Program: Preliminary Data.
AB  - OBJECTIVES: To describe the Texas Elder Abuse and Mistreatment Institute Forensic
      Assessment Center Network (TEAM-FACN), a novel statewide elder mistreatment (EM)
      virtual assessment program using low-cost videophone technology and innovative
      web-based coordination to connect an Adult Protective Services (APS) agency and
      its clients, rural and urban, to a centralized geriatric and EM expert medical
      team for virtual in-home assessments. DESIGN: Descriptive. SETTING: Community.
      PARTICIPANTS: APS clients aged 18 and older. INTERVENTION: Virtual and in-home
      assessments. MEASUREMENTS: Program use and type of services provided. RESULTS: In
      the first 8 months, 300 APS clients from all regions of the state were referred
      for assessment. Outcomes realized include a quadrupling in number of client
      assessments. TEAM-FACN physicians provided an average of 2 services, which
      included 216 mental health assessments, with 123 conducted virtually; 42 medical
      assessments; 45 guardianship filings; 5 employee misconduct registry reviews; and
      more than 230 interdisciplinary team meetings to discuss case findings, safety
      plans, and medical and social interventions. CONCLUSION: TEAM-FACN provides an
      innovative and viable way to increase access of urban and rural older and adults
      who are being mistreated to expert geriatric and EM protective service
      assessments.

PMID- 30221759
TI  - Impact of social disadvantage on cerebral palsy severity.
AB  - AIM: To investigate the impact of socio-economic disadvantage on indicators of
      cerebral palsy (CP) severity - motor impairment, intellectual disability, and the
      presence of severe comorbidities - in children with CP in Australia. METHOD: Data
      from the Australian Cerebral Palsy Register were analysed. Socio-economic
      disadvantage was assessed using maternal age, maternal country of birth, and a
      measure of neighbourhood socio-economic status (SES) at the time of the child's
      birth. Descriptive bivariate analysis, trend analysis, risk ratios, and mediation
      analysis were undertaken to examine the impact of disadvantage on the indicators
      of CP severity. RESULTS: A socio-economic gradient was demonstrated with an
      increasing proportion of children with non-ambulant status, at least moderate
      intellectual disability, and the presence of severe comorbidities (having
      epilepsy, functional blindness, bilateral deafness, and/or no verbal
      communication) with decreasing neighbourhood SES, adolescent motherhood, and
      maternal minority ethnicity. INTERPRETATION: In Australia, socio-economic
      disadvantage at birth impacts adversely on CP severity at age 5 years. By
      identifying that socio-economically disadvantaged children with CP are at greater
      risk of more severe functional outcomes, we can inform targeted interventions at
      the family and neighbourhood level to reduce these inequities for children with
      CP. WHAT THIS PAPER ADDS: Socio-economic disadvantage is associated with
      increased severity of cerebral palsy functional outcomes. This encompasses low
      neighbourhood socio-economic status, adolescent motherhood, and maternal minority
      ethnicity.

PMID- 30221761
TI  - Disulfide reductase systems in liver.
AB  - Intermediary metabolism and detoxification place high demands on the disulfide
      reductase systems in most hepatocyte subcellular compartments. Biosynthetic,
      metabolic, cytoprotective and signalling activities in the cytosol; regulation of
      transcription in nuclei; respiration in mitochondria; and protein folding in
      endoplasmic reticulum all require resident disulfide reductase activities. In the
      cytosol, two NADPH-dependent enzymes, glutathione reductase and thioredoxin
      reductase, as well as a recently identified NADPH-independent system that uses
      catabolism of methionine to maintain pools of reduced glutathione, supply
      disulfide reducing power. However the necessary discontinuity between the cytosol
      and the interior of organelles restricts the ability of the cytosolic systems to
      support needs in other compartments. Maintenance of molecular- and charge
      gradients across the inner-mitochondrial membrane, which is needed for oxidative
      phosphorylation, mandates that the matrix maintain an autonomous set of NADPH
      dependent disulfide reductase systems. Elsewhere, complex mechanisms mediate the
      transfer of cytosolic reducing power into specific compartments. The redox needs
      in each compartment also differ, with the lumen of the endoplasmic reticulum, the
      mitochondrial inter-membrane space and some signalling proteins in the cytosol
      each requiring different levels of protein oxidation. Here, we present an
      overview of the current understanding of the disulfide reductase systems in major
      subcellular compartments of hepatocytes, integrating knowledge obtained from
      direct analyses on liver with inferences from other model systems. Additionally,
      we discuss relevant advances in the expanding field of redox signalling.

PMID- 30221760
TI  - The Unproductively Conducted Productive Visit.

PMID- 30221762
TI  - Lactobacillus plantarum CQPC06 Activity Prevents Dextran Sulfate Sodium-Induced
      Colitis by Regulating the IL-8 Pathway.
AB  - : Lactobacillus plantarum CQPC06 (LP-CQPC06) is a newly discovered lactic acid
      bacterial strain. Here, the beneficial effects of this strain on C57BL/6J mice
      with dextran sulfate sodium-induced colitis were investigated. LP-CQPC06 was more
      resistant to gastric acid and bile salts than L. delbrueckii subsp. bulgaricus
      (LB). In the DSS-induced colitis mouse model, LP-CQPC06 treatment decreased the
      colon weight/length ratio and increased the colon length as compared to untreated
      mice with DSS-induced colitis. LP-CQPC06 also reduced the serum levels of
      interleukin 8 (IL-8), IL-1, tumor necrosis factor alpha, and macrophage
      inflammatory protein-1 alpha, as well as reducing levels of myeloperoxidase (MPO)
      and nitric oxide (NO) in the colon tissues of mice with DSS-induced colitis. In
      all cases, the effects of LP-CQPC06 were significantly stronger than those of LB.
      Quantitative polymerase chain reactions and western blots indicated that LP
      CQPC06 increased the mRNA and protein expression levels of neuronal nitric oxide
      synthase, endothelial nitric oxide synthase, and nuclear factor of kappa light
      polypeptide gene enhancer in B-cells inhibitor alpha, while decreasing the
      expression levels of inducible nitric oxide synthase, nuclear factor kappa-beta,
      C-X-C motif chemokine receptor 1 (CXCR1), and CXCR2. Thus, L. plantarum CQPC06
      had a good protective effect against colitis in a mouse model via the IL-8
      pathway. Therefore, L. plantarum CQPC06 might have potential uses as a probiotic
      for colonic protection. PRACTICAL APPLICATION: In this study, a newly discovered
      lactic acid bacteria was investigated. This bacterial strain had a good
      prophylactic effect against colitis in a mouse model, and might have potential
      utility as a probiotic.

PMID- 30221763
TI  - Cardiovascular disease and related risk factors in adults with cerebral palsy: a
      systematic review.
AB  - AIM: To summarize the literature on the prevalence of cardiovascular disease
      (CVD), risk factors of CVD, and CVD-related mortality in adults with cerebral
      palsy (CP). METHOD: A systematic review was conducted by searching the PubMed,
      Embase, MEDLINE (Ovid), Cochrane, and CINAHL databases. Selection criteria
      included adults with CP aged 18 years or over. Methodological quality was
      assessed using the Newcastle-Ottawa scale for observational studies. Data were
      reported descriptively. RESULTS: Nineteen studies met the inclusion criteria.
      Only one study reported directly on the presence of CVD in adults with CP, which
      found adults with CP reported greater CVD conditions than adults without CP (15.1
      vs 9.1%, p<0.001). The most commonly reported risk factor of CVD in adults with
      CP was overweight/obesity. Five studies included data on CVD-related mortality in
      persons with CP, where CVD-related and circulatory system-related deaths were
      elevated and more common at a younger age in adults with CP than in the general
      population. INTERPRETATION: The prevalence of CVD and the risk of death because
      of CVD in this population seems increased, though the knowledge base is
      fragmented by studies that are small in size and geographically isolated. Further
      research is required to understand prevalence of risk factors among adults with
      CP, in particular overweight/obesity. WHAT THIS PAPER ADDS: Overweight and
      obesity are risk factors of cardiovascular disease (CVD) that are commonly
      reported in adults with cerebral palsy (CP). CVD-related and circulatory system
      related deaths are elevated in individuals with CP compared to the general
      population.

PMID- 30221764
TI  - Isolated seizures during the first episode of relapsing myelin oligodendrocyte
      glycoprotein antibody-associated demyelination in children.
AB  - Myelin oligodendrocyte glycoprotein (MOG) antibodies have a strong association
      with acute disseminated encephalomyelitis (ADEM) in children, and bilateral and
      recurrent optic neuritis in children and adults. Recent reports suggest that
      seizures and encephalopathy may occur in children and adults with MOG antibody
      associated disease. We describe the clinical, laboratory, and radiological course
      of four MOG antibody-positive children who first presented with isolated seizures
      without fulfilling clinical or radiological criteria for ADEM or other central
      nervous system demyelination syndromes, who months to years later developed more
      typical demyelination. This case series highlights a novel observation that
      isolated seizures in the absence of ADEM may be the index presentation for MOG
      antibody-associated disease, which should therefore be considered a form of
      autoimmune epilepsy. It would be reasonable to test for MOG antibodies in
      children with seizures accompanied by subtle inflammatory changes on magnetic
      resonance imaging or cerebrospinal fluid analyses, particularly if followed by
      demyelination, given the clinical and therapeutic implications of an expedited
      diagnosis in minimizing long-term disability. WHAT THIS PAPER ADDS: Isolated
      seizures in the absence of acute disseminated encephalomyelitis may be the index
      presentation for myelin oligodendrocyte glycoprotein antibody-associated
      demyelination.

PMID- 30221766
TI  - Snapshot quiz.

PMID- 30221767
TI  - Trials and tribulations of neoadjuvant therapy in pancreatic cancer.

PMID- 30221769
TI  - Snapshot quiz.

PMID- 30221765
TI  - Survey Analysis of the Use, Effectiveness, and Patient-Reported Tolerability of
      Inhaled Oxygen Compared With Injectable Sumatriptan for the Acute Treatment of
      Cluster Headache.
AB  - OBJECTIVE: In this secondary analysis of the Clusterbusters(r) Medication Use
      survey, the use, effectiveness, and tolerability of inhaled oxygen were
      investigated and compared with injectable sumatriptan. We also sought to
      understand the predictors of medication response. BACKGROUND: Inhaled oxygen is a
      mainstay abortive intervention in cluster headache but is not approved by the
      Food and Drug Administration (FDA). Unlike injectable sumatriptan, the only FDA
      approved pharmacologic intervention for cluster headache, oxygen can be used
      multiple times a day, which is highly relevant for a condition with numerous
      daily attacks. In addition to obstacles in obtaining oxygen therapy, optimal
      oxygen delivery (ie, mask, flow rate) is not uniformly employed in cluster
      headache. These factors lead to underuse and imprecise therapeutic response
      rates. METHODS: A secondary analysis was conducted using deidentified data from
      the Clusterbusters(r) Medication Use survey, which was modeled after previously
      published surveys and available online. Subjects were recruited from headache
      clinics and cluster headache websites. Most responses were chosen from a list;
      others were free-texted. The final analysis included responses from 493 adult
      participants with a validated diagnosis of cluster headache. This analysis of
      deidentified data from the Clusterbusters(r) Medication Use survey received
      institutional approval. RESULTS: The most commonly used delivery system used by
      subjects was a non-rebreather-type mask. The use of oxygen flow rates >10 L/min
      was a positive predictor of medication response (OR = 2.36, P = .016). Among
      those who used flow rates >10 L/min, both inhaled oxygen (81.5%) and injectable
      sumatriptan (80.5%) were efficacious and did not differ significantly from each
      other in any specific group examined. At flow rates >10 L/min, positive
      predictors of oxygen response were male gender (OR = 2.07, P = .031) and
      cigarette smoking (current or historical; OR = 2.25, P = .017). Among the groups
      examined, there were no predictors of sumatriptan response. Most comments about
      side effects and concerns were directed at triptans. CONCLUSION: Therapeutic
      response to inhaled oxygen at sufficiently high flow rates (>10 L/min) had
      comparable efficacy to that of injectable sumatriptan for the acute treatment of
      cluster headache. Other factors in oxygen delivery (ie, flow rate changes) should
      be explored for optimization of therapy. The reasons for improved oxygen response
      in males and those with a cigarette smoking history require further exploration.
      While both oxygen and sumatriptan can be effective in the management of cluster
      headache, patient-reported side effects and concerns were more commonly directed
      at triptan medications. Current restrictions on access to inhaled oxygen, which
      exist at many levels, limit the therapeutic options available for patients with
      cluster headache, thereby doing a disservice to this patient population and the
      providers who deliver their care.

PMID- 30221771
TI  - Beyond body structure in intrathecal baclofen therapy.

PMID- 30221772
TI  - Protective Effect of Grape Seed Procyanidins against H2 O2 -Induced Oxidative
      Stress in PC-12 Neuroblastoma Cells: Structure-Activity Relationships.
AB  - : To establish a structure-activity relationship for procyanidins, we verified
      the cyto-protective effect of 13 grape seed procyanidins, ranging from monomers
      to trimers against H2 O2 -induced oxidative stress in PC-12 neuroblastoma cells.
      Our study demonstrated some procyanidins were able to significantly protect PC-12
      cells from the H2 O2 -induced cytotoxicity suggesting they possess
      neuroprotective effects against oxidative stress. Procyanidins' protective
      effects against oxidative stress mainly depended on their polymerization degree
      in addition to their structural features. A positive correlation was found
      between procyanidins' polymerization degree and the protective effect against
      oxidative stress in PC-12 cells. The presence of 3- or 3'-galloylated groups in
      the C-ring of procyanidin molecules significantly increased their protective
      activity as well. These results demonstrated that galloylated high-molecular-mass
      procyanidins would be of more interesting as promising antioxidant natural
      compounds. This work for the first time demonstrated the structure-activity
      relationships of 13 procyanidins' antioxidative stress activity, which could have
      a significant impact on future development of procyanidins for healthy food
      products or drugs to treat disease such as neurodegenerative disorders. PRACTICAL
      APPLICATION: This work evaluated the protective effect of procyanidins against
      oxidative stress in PC-12 neuroblastoma cells and established their activity
      structure relationships, which provides useful cellular evidence for the further
      investigating the structure-optimizing and function-exploiting of procyanidins.

PMID- 30221773
TI  - Learning from consumers: An eDelphi study of Australian mental health consumers'
      priorities for recovery-oriented curricula.
AB  - BACKGROUND/AIM: Mental health reform in Australia emphasises recovery,
      partnership working and prioritises consumers' needs over professionals'.
      Occupational therapy students must develop capabilities for working in this way.
      Learning from consumers' lived experience of mental illness and recovery is
      considered critical to developing such capabilities and aligns with occupational
      therapy programme accreditation for consumer involvement in designing, delivering
      and evaluating curricula. No definitive capability standards exist to inform
      curricula and little is known about Australian mental health consumers' preferred
      modes of involvement in health professional education. This study sought to
      identify consumers' priorities for curricula, and ways in which they would like
      to participate in entry-level student education. METHODS: An eDelphi study
      utilising the Policy Delphi approach was employed. Consensus by 70% of
      participants was set as the standard for item inclusion. The first round asked
      open questions about participants' priorities for recovery-oriented curricula,
      their experiences with mental health workers and asked participants to identify
      their preferred methods of participating in education. Items generated were rated
      in subsequent rounds until consensus was reached in round three. RESULTS: Twenty
      eight participants completed round one, 18 completed round two and 14 completed
      round three. Five core values and 171 curriculum priorities, forming 12
      capability domains, reached consensus. Each capability domain comprised knowledge
      and understanding; skills and abilities; and behaviours and actions. Ten ways of
      participating in mental health curricula in entry-level occupational therapy
      programmes were identified, with an emphasis on active participation in design,
      delivery and review of curricula. CONCLUSION: These findings highlight important
      capabilities from consumers' perspectives, suggesting key content for curricula.
      Active roles in designing, delivering and evaluating curricula were preferred,
      providing some guidance for educators seeking to involve consumers. Further
      research is required to refine these priorities, and to evaluate acceptability,
      feasibility and efficacy of varying modes of consumer involvement.

PMID- 30221774
TI  - The transformative and informative nature of elections: Representation, schism,
      and exit.
AB  - In democratic elections, constituents may view unconventional or non-prototypical
      candidates as attempting to reshape their national identity in the wrong
      direction. When a non-prototypical candidate actually steps into a leadership
      role, the group's consensual view of their prototype may shift to position this
      new leader as prototypical. This process should be bound in member consensus,
      evidenced by the leader's successful election. The current work examines American
      Republicans (N = 297) and Democrats (N = 322) before and after the 2016 US
      election. We focus on Republicans' interpretations of their candidate Donald
      Trump's prototypicality and ability to bolster or subvert their party identity
      pre-election. Post-election, we examine changes to these processes, related in
      part to Republicans' homogenized view of Trump's prototypicality. In comparison,
      we examine these processes in the Democratic Party. Results suggest that whereas
      Democrats increased in their desire to leave their party, Republicans decreased
      in their desire to leave their party, an effect that is related to increasing
      perceptions of Trump's prototypicality and representation of the Republican
      Party. These findings have important implications for how the contexts of
      elections rapidly shape party identity through the election of leaders such as
      Trump.

PMID- 30221775
TI  - Training proprioception with sound: effects of real-time auditory feedback on
      intermodal learning.
AB  - Our study analyzed the effects of real-time auditory feedback on intermodal
      learning during a bilateral knee repositioning task. Thirty healthy participants
      were randomly allocated to control and experimental groups. Participants
      performed an active knee joint repositioning task for the four target angles (20
      degrees , 40 degrees , 60 degrees , and 80 degrees ) bilaterally, with or without
      additional real-time auditory feedback. Here, the frequency of auditory feedback
      was mapped to the knee's angle range (0-90 degrees ). Retention measurements were
      performed on the same four angles, without auditory feedback, after 15 min and 24
      hours. A generalized knee proprioception test was performed after the 24-h
      retention measurement on three untrained knee angles (15 degrees , 35 degrees ,
      and 55 degrees ). Statistical analysis revealed a significant enhancement of knee
      proprioception, shown as a lower knee repositioning error with auditory feedback.
      This enhancement of proprioception also persisted in tests performed between the
      5th and 6th auditory-motor training blocks (without auditory feedback).
      Enhancement in proprioception also remained stable during retention measurements
      (after 15 min and 24 h). Similarly, enhancement in the generalized proprioception
      on untrained knee angles was evident in the experimental group. This study
      extends our previous findings and demonstrates the beneficial effects of real
      time auditory feedback to facilitate intermodal learning by enhancing knee
      proprioception in a persisting and generalized manner.

PMID- 30221776
TI  - Effects of transcranial photobiomodulation with near-infrared light on sexual
      dysfunction.
AB  - OBJECTIVES: Transcranial photobiomodulation (t-PBM) consists of the delivery of
      near-infrared (NIR) or red light to the scalp designed to penetrate to subjacent
      cortical areas of the brain. NIR t-PBM has recently emerged as a potential
      therapy for brain disorders. This study assessed the efficacy of repeated
      sessions of NIR t-PBM on sexual dysfunction. METHODS: We performed a secondary
      analysis of a double-blind clinical trial on t-PBM for major depressive disorder
      (MDD). Twenty individuals received NIR t-PBM (n = 9) or sham therapy (n = 11)
      twice a week for 8 weeks. Sexual desire, arousal, and orgasm were assessed using
      the Systematic Assessment for Treatment-Emergent Effects-Specific Inquiry (SAFTEE
      SI). RESULTS: The mean improvement in sexual function (decrease in SAFTEE sex
      total score) in subjects receiving t-PBM in NIR-mode was significantly greater
      than in subjects receiving sham-mode in the whole sample (NIR [n = 9] -2.55 +/-
      1.88 vs. sham [n = 11] -0.45 +/- 1.21; z = 2.548, P = 0.011]) and in the
      completers (NIR [n = 5] -3.4 +/- 1.95 vs. sham [n = 7] -0.14 +/- 1.21; z = 2.576,
      P = 0.010]). CONCLUSION: This exploratory study with a small sample size
      indicates that repeated sessions of NIR t-PBM may be associated with therapeutic
      effects on sexual dysfunction. The latter appeared unrelated to the
      antidepressant effect of t-PBM in our cohort. Lasers Surg. Med. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30221777
TI  - Ambulatory urodynamics monitoring - a video demonstration.
AB  - AIMS: To present a narrated video designed to demonstrate the steps involved in
      performing and interpreting ambulatory urodynamics monitoring (AUM). METHODS:
      This video provides an overview of the role of AUM in clinical practice and
      describes the process of performing AUM using solid state microtip transducers
      and the MMS / Laborie Luna ambulatory recorder. Line placement, calibration and
      the urodynamic protocol are discussed along with descriptions of provocation
      tests that can be used during AUM. Examples of AUM traces are reviewed
      demonstrating common findings eg detrusor overactivity, urodynamic stress
      incontinence and voiding difficulties. Good urodynamic practice in relation to
      the interpretation of AUM is presented. Its application in clinical practice is
      often limited due to the cost of equipment (particularly the microtip transducers
      which range from L1200-L2500) and appropriate decontamination of the transducers
      (in this unit an anti-sporacidal 3 stage wipe system is employed (Tristel)
      however, many hospital infection control teams do not consider this sufficient so
      disposable water or air filled lines are used). Other limitations include the
      requirement for additional training and the time necessary to perform the test.
      RESULTS: This video will educate and inform health care professionals regarding
      AUM so that they may consider its use in their armamentarium of investigations of
      lower urinary tract function and be able to counsel patients appropriately should
      they choose to refer them to an alternative provider for further investigation if
      they do not have direct access in their service. CONCLUSION: AUM is a second line
      investigation of lower urinary tract dysfunction used in patients where
      conventional urodynamics have failed to make a diagnosis or replicate their
      symptoms. They allow for a more physiological assessment of bladder function.
      Protocols may vary from 1 h to 24 h but are dependent on re-creation of patient's
      symptoms.

PMID- 30221778
TI  - Inglorious glorification and attachment: National and European identities as
      predictors of anti- and pro-immigrant attitudes.
AB  - Anti-immigrant attitudes are not only widespread among Eurosceptic nationalists,
      but also among people who feel that immigration threatens European values and
      identity. We therefore assumed that the connection between nationalism and
      xenophobia can only partially explain the rise of hostile attitudes in the post
      2015 period. In two online surveys (N = 1,160), we compared how (a) glorification
      versus attachment and (b) national versus European identity can predict anti
      immigrant and anti-Muslim attitudes in Hungary. In the first study, national and
      European glorification predicted higher anti-immigrant and anti-Muslim prejudice.
      However, attachment with Europe predicted positive, while attachment with Hungary
      predicted negative attitudes towards immigrants. We replicated this pattern in a
      second study and found that the different predictions of national versus European
      identities were mediated by attitudes towards the EU. Eurosceptic attitudes were
      associated with increased hostility towards both immigrants and Muslim people and
      reflected a perceived contradiction between the interest of the nation and that
      of the EU. We conclude that for a better understanding of intergroup hostility
      towards Muslim immigrants in Europe, we need to simultaneously consider the
      psychological phenomenon of ingroup glorification and the values and norms of the
      social categories with which people identify.

PMID- 30221779
TI  - The contribution of participant, treatment, and outcome factors to treatment
      satisfaction.
AB  - Treatment satisfaction, which refers to the positive appraisal of process and
      outcome attributes of a treatment, is a prominent indicator of quality care.
      Although it is known that participant, treatment, and outcome factors influence
      treatment satisfaction, it remains unclear which factors contribute to
      satisfaction with each process and outcome attribute. In this study, we examined
      the extent to which participant (age, gender, education, race, employment),
      treatment (type of therapy, method of assignment to therapy), and outcome (self
      reported improvement in outcome) factors contribute to satisfaction with the
      process and outcome attributes of therapies for insomnia. This study consists of
      a secondary analysis of data obtained from a partially randomized preference
      trial in which persons with chronic insomnia (N = 517) were assigned to treatment
      randomly or by preference. Four types of behavioral therapies were included:
      sleep hygiene, stimulus control therapy, sleep restriction therapy, and multi
      component therapy. Self-reported improvement in insomnia and satisfaction were
      assessed with validated measures at post-test. Multiple regression analysis was
      used to examine which factors influenced satisfaction with each treatment
      attribute. The findings showed that treatment and outcome, more so than
      participant, factors influenced satisfaction with the process and outcome
      attributes of the behavioral therapies for insomnia. Future research on
      satisfaction should explore the contribution of treatment (type and preference
      matching) and outcome factors on satisfaction to build a better understanding of
      treatment attributes viewed favorably. Such understanding has the potential to
      inform modifying or tailoring treatments to improve their acceptance to
      participants and optimize their effectiveness.

PMID- 30221780
TI  - SOX11: a potentially useful marker in surgical pathology: a systematic analysis
      of SOX11 expression in epithelial and non-epithelial tumours.
AB  - AIMS: SOX11 is known as an essential transcription factor for regulating
      neurogenesis. Recently, SOX11 has been suggested to be a diagnostic marker and
      oncogene because of its significant expression in mantle cell lymphoma (MCL).
      However, SOX11 expression in other tumour types has not yet been extensively
      studied. METHODS AND RESULTS: Herein, we examined SOX11 expression in 2026 cases
      of neuroectodermal, germ cell, mesenchymal and epithelial tumours by
      immunohistochemistry. SOX11 was consistently expressed in all neuroectodermal
      tumours with neural differentiation, as well as in immature teratomas revealing
      neurogenesis. Less frequently, SOX11 expression was observed in only 50% of
      astrocytomas and 24% of malignant peripheral nerve sheath tumours, and was mainly
      sporadic and weak/intermediate. In epithelial tumours, significant SOX11
      expression was identified in 97% of salivary ductal carcinomas (SDCs) and a high
      percentage of high-grade neuroendocrine carcinomas (NECs), especially the small
      cell lung carcinomas (68%), and was absent in most other carcinomas, except for
      less and/or focal and weak expression in adenocarcinomas from the lung, genital
      tract and breast, and salivary adenoid cystic carcinomas and epithelial
      myoepithelial carcinomas. In mesenchymal tumours, in addition to MCLs, prominent
      SOX11 expression was observed in 90% of rhabdomyosarcomas and all myxoid/round
      cell liposarcomas (MRCLs). Less frequent and/or focal and weak expression was
      observed in lymphoblastic, Burkitt and follicular lymphomas, synovial sarcoma and
      angiosarcoma. CONCLUSION: SOX11 showed prominent expression in neuroectodermal
      tumours with neural differentiation, high grade-NEC, SDC, rhabdomyosarcoma and
      MRCL. The high sensitivity and specificity of SOX11 in SDC and MRCL make it a
      useful diagnostic marker.

PMID- 30221781
TI  - On-the-ground health and safety experiences of non-union casino hotel workers: A
      focus-group study stratified by four occupational groups.
AB  - OBJECTIVES: To understand the health- and safety-related experiences of specific
      occupations among non-union casino hotel employees to identify processes leading
      to worker health and safety risks. METHODS: Using purposive, criterion sampling,
      61 workers participated in 13 recorded focus groups (FGs). A semi-structured
      topic guide addressed work-related health and safety impacts, workplace hazards,
      and management responses, among others. FG transcripts were analyzed following
      grounded theory methodology. Demographic and occupational health information was
      collected via survey. RESULTS: Codes (97) were collapsed into seven themes:
      activities/exposures negatively affecting health/safety; barriers to
      health/safety; injury/pain occurrences; coping mechanisms; job vulnerability;
      management policies/enforcement; lack of management concern for employees. From
      these themes emerged the Dynamic Theoretical Framework of Employee Health and
      Safety Risk. CONCLUSIONS: "Management's lack of concern" creates a negative
      environment whereby employer-controlled factors jeopardize employees' health and
      safety. Interventions targeting management's lack of concern for employee health
      and safety could favorably change work-based risks.

PMID- 30221782
TI  - Study of aldehyde oxidase by micellar electrokinetic chromatography separation of
      O6 -benzylguanine and 8-oxo-O6 -benzylguanine.
AB  - A separation method for O6 -benzylguanine (O6 -BG) and 8-oxo-O6 -benzylguanine (8
      oxo-O6 -BG) is developed by using MEKC. This study includes the optimization of
      separation and incubation parameters for both off-line and on-line procedures.
      The BGE consisted of 25 mM sodium phosphate buffer-methanol (70:30, v/v),
      apparent pH 7.4, in which SDS and methyl-beta-cyclodextrin were dissolved
      yielding final concentrations of 50 and 15 mM, respectively. Separations were
      performed at 15 kV using an untreated fused-silica capillary (40 cm length,
      effective length is 30 cm) with the detection wavelength at 195 nm. The capillary
      was kept at 15 degrees C. Good performances were demonstrated for the
      repeatability and linearity. The LOQ was determined to be 14 MUM for 8-oxo-O6 -BG
      (S/N = 10). The accuracy values showed a bias of +7.9% for 50 MUM and -7.0% for
      100 MUM. Premix and transverse diffusion of laminar flow profiles (TDLFP) methods
      were used for on-line mixing and reaction of the substrate O6 -BG with aldehyde
      oxidase. Both procedures were successful in mixing as well as subsequent
      separation of the substrate and the metabolite, while the repeatability of TDLFP
      (14.7% (n = 3)) was much better than the premix technique.

PMID- 30221783
TI  - Incidence and predictors of MRI scan utilization in MRI-conditional pacemaker
      recipients: A multicenter experience.
AB  - BACKGROUND: Patient characteristics, higher device cost, and vendor contracts
      likely prevent use of magnetic resonance imaging (MRI)-conditional pacemakers
      (MRC) in all pacemaker (PM)-eligible patients. We sought to identify the
      incidence and predictors of MRI scan utilization in MRC recipients. METHODS:
      Patients receiving an MRC or non-MRI-conditional PM (NMRC) at four centers were
      included. Incidence of MRI scans following PM insertion was obtained from
      hospital records and patient phone calls. RESULTS: Of 1,244 patients (74 +/- 12
      years, 54.6% male), 927 had MRC and 317 had NMRC. At baseline, MRC recipients had
      a higher incidence of atrial tachycardia and MRI risk factors (syncope, recurrent
      falls, neurological disease, severe musculoskeletal disease, malignancy). In the
      MRC group, more patients had commercial health insurance (26% vs 15%, P < 0.001).
      Sixty MRC patients (6.5%) had an MRI during 21 +/- 17 months' follow-up. Using
      the Weilbull parametric survival model, the projected percentage of MRC patients
      receiving an MRI scan at 7- and 11-year follow-up were 45% and 73%, respectively.
      By multivariate regression, a prior history of MRI (odds ratio [OR] 4.5, 95%
      confidence interval [CI] 2.2-9.1, P < 0.001) and active smoking (OR 2.65, 95% CI
      1.1-6.7, P  =  0.039) independently predicted the performance of an MRI following
      MRC implant. CONCLUSIONS: In this MRC cohort, MRI scan utilization during follow
      up was low but projection analyses showed a higher incidence over the lifetime of
      the MRC. A history of prior MRI and active smoking independently predicted the
      performance of an MRI scan during follow-up.

PMID- 30221784
TI  - Bioprosthetic tricuspid valve dysfunction in patients with transvalvular or
      epicardial pacing leads.
AB  - BACKGROUND: Dysfunction of native tricuspid valves due to transvenous pacing
      leads is well described. Patients with bioprosthetic tricuspid valve (BTV) who
      need ventricular pacing are often advised epicardial lead placement to avoid
      potential damage to the BTV although there are no data to support this.
      OBJECTIVE: The aim of the study was to assess the frequency of BTV dysfunction in
      patients with permanent transvenous right ventricular pacemaker lead and compare
      it to patients with epicardial leads. METHODS: A retrospective review of patients
      with BTV with ventricular pacing lead was conducted. Demographics, lead, BTV, and
      echocardiographic data were collected. Frequency of BTV dysfunction (moderate or
      severe) regurgitation or stenosis was compared between epicardial and
      transvalvular lead groups. RESULTS: Forty-six patients with BTV and ventricular
      pacing lead (20 transvalvular and 26 epicardial leads) were identified. Mean age
      was 46 years with the majority being female (85%) and with rheumatic heart
      disease (87%). Both groups were similar in age, sex, and indications for BTV.
      Mean echocardiographic follow-up was for 5.5 years (+/-4.1 years). BTV
      dysfunction was similar between the transvalvular group with six (30%) patients
      and the epicardial group with five (19.2%) patients. The incidence of BTV
      dysfunction was greater in patients in sinus rhythm compared to patients in
      atrial fibrillation (50% vs 10%, P  =  0.004). CONCLUSION: Development of BTV
      dysfunction is similar in patients with transvalvular ventricular leads and
      epicardial leads. The incidence of BTV dysfunction was higher in patients with
      sinus rhythm compared to atrial fibrillation.

PMID- 30221785
TI  - Comparison of the nutritional content of the captive and wild diets of the
      critically endangered mountain chicken frog (Leptodactylus fallax) to improve its
      captive husbandry.
AB  - It is vital to provide appropriate nutrition to maintain healthy populations in
      conservation breeding programs. Knowledge of the wild diet of a species can be
      used to inform captive diet formulation. The nutritional content of the wild diet
      of the critically endangered mountain chicken frog (Leptodactylus fallax) is
      unknown, like that of most amphibians. In this study, we analyzed the nutritional
      content of food items that comprise 91% of the wild diet of L. fallax, by dry
      weight of food items, and all food items offered to captive L. fallax at ZSL
      London Zoo and Jersey Zoo. We subsequently compared the nutritional content of
      the wild diet and captive diet at ZSL London Zoo consumed by L. fallax. To the
      authors' knowledge, this is the first study to directly compare the nutritional
      content of the wild and captive diets of an anuran amphibian. The captive diet at
      ZSL London Zoo, without dusting of nutritional supplements, was higher in gross
      energy and crude fat and lower in ash, calcium and calcium:phosphorus ratio than
      the wild diet. Most of the food items in the captive diets had a high omega
      6:omega-3 fatty acid ratio and in the wild diet had a low omega-6:omega-3 fatty
      acid ratio. We recommend a combination of modifications to the captive diets to
      better reflect the nutritional content of the wild diet. Nutritional analysis of
      captive and wild diets is recommended for other species in conservation breeding
      programs to improve captive husbandry and ultimately fitness.

PMID- 30221786
TI  - Frequent false-negative immunohistochemical staining with IDH1 (R132H)-specific
      H09 antibody on frozen section control slides: a potential pitfall in glioma
      diagnosis.
AB  - AIMS: Intraoperative consultation using frozen sections (FSs) is an integral
      component of clinical practice. As a quality control measure, FS diagnosis is
      subsequently compared with the findings on a FS control slide. These control
      slides can be used for immunohistochemistry, and the immunohistochemical
      performance in FS controls is known to be antibody-dependent. Isocitrate
      dehydrogenase (IDH) is mutated in >80% of lower-grade infiltrating gliomas in
      adults and in ~10% of glioblastomas, with IDH1 (R132H) being the most common
      mutation. IDH status is used as a major classifier of glioma. An IDH1 (R132H)
      specific antibody (H09) has been accepted as a robust surrogate for genetic
      testing. In this study, we aimed to determine how previous freezing and thawing
      affects IDH1 immunohistochemistry. METHODS AND RESULTS: Thirty cases of IDH1
      (R132H)-mutant diffuse glioma, which were originally assessed on FSs, were
      retrieved. The positive IDH1 (R132H) status of each case was previously
      determined with pyrosequencing and H09 immunohistochemistry on permanent
      sections. The FS control tissue of each case was immunostained with H09 antibody.
      Among 30 gliomas, 25 showed negative reactivity on FS control slides, whereas, in
      the remaining five, the staining was uninterpretable, owing to a high diffuse
      background. Of the former 25 specimens, 20 showed at least focal areas with
      variably increased levels of background staining, whereas the remaining five
      specimens showed a relatively pristine background. CONCLUSIONS: We conclude that
      IDH1 (R132H)-specific (H09) immunohistochemistry often results in false-negative
      reactions on FS controls with focally increased background staining, and this
      application should be avoided in clinical practice.

PMID- 30221787
TI  - Assessing female reproductive status of spectral tarsier (Tarsius tarsier) using
      fecal steroid hormone metabolite analysis.
AB  - The wild population of spectral tarsier is declining and attempts to breed the
      species in captivity have been of limited success. One possible reason for this
      is that information on the reproductive biology of Tarsius tarsier is extremely
      limited and data on the species reproductive physiology are completely lacking.
      We validated fecal estrogen (E-total) and progesterone metabolite (5-P-3OH)
      measurements for monitoring female ovarian activity and pregnancy. We used this
      approach to provide the first data on cycle and pregnancy length based on
      endocrine information in this species. We collected regular fecal samples in
      combination with observations on socio-sexual behaviors for a maximum of 15
      months from three females maintained at Primate Research Center of Bogor
      Agricultural University, Indonesia. Hormonal profiles indicated that behavioral
      estrus was associated with marked elevations in fecal E-total concentrations
      followed by increases in 5-P-3OH levels indicating luteal function. Pregnancy was
      characterized by low levels of E-total and 5-P-3OH during the first month and
      markedly rising concentrations thereafter. An ovarian cycle length of 21.7 +/-
      5.7 days was found. Gestation length was 128d (live infant), 131d (stillbirth),
      and 164d (death of mother and infant due to dystocia). Despite the small sample
      size, the study demonstrates the overall validity of fecal sex hormone metabolite
      measurements for reproductive monitoring in female T. tarsier, as such, the
      methods described here may ultimately help to improve the breeding management of
      the species in captivity. They may also offer new opportunities for investigating
      basic questions of tarsier reproductive biology in the wild by using fecal
      hormone metabolite analysis to diagnose pregnant animals and determine
      reproductive rates in relation to ecological and other factors influencing
      tarsier reproduction. Thus, non-invasive assessment of female reproductive
      condition as described here may ultimately contribute to facilitate in and ex
      situ conservation efforts of this endangered primate species.

PMID- 30221788
TI  - Constitutive cardiomyocyte proliferation in the leopard gecko (Eublepharis
      macularius).
AB  - Although the contractile function of the heart is universally conserved, the
      organ itself varies in structure across species. This variation includes the
      number of ventricular chambers (one, two, or an incompletely divided chamber),
      the structure of the myocardial wall (compact or trabeculated), and the
      proliferative capacity of the resident cardiomyocytes. Whereas zebrafish are
      capable of comparatively high rates of constitutive cardiomyocyte proliferation,
      humans and rodents are not. However, for most species, the capacity to generate
      new cardiomyocytes under homeostatic conditions remains unclear. Here, we
      investigate cardiomyocyte proliferation in the lizard Eublepharis macularius, the
      leopard gecko. As for other lizards, the leopard gecko heart has a partially
      septated ventricular lumen with a trabeculated myocardial wall. To test our
      hypothesis that leopard gecko cardiomyocytes routinely proliferate, we performed
      5-bromo-2'-deoxyuridine incorporation and immunostained for the mitotic marker
      phosphorylated histone H3 (pHH3) and the DNA synthesis phase (S phase) marker
      proliferating cell nuclear antigen (PCNA). Using double immunofluorescence, we co
      localized pHH3 or PCNA with the cardiomyocyte marker myosin heavy chain (MHC). We
      found that ~0.5% of cardiomyocytes were mitotically active (pHH3+/MHC+), while
      ~10% were in S phase (PCNA+/MHC+). We also determined that cell cycling by gecko
      cardiomyocytes is not impacted by caudal autotomy (tail loss), a dramatic form of
      self-amputation. Finally, we show that populations of cardiac cells are slow
      cycling. Overall, our findings provide predictive evidence that geckos may be
      capable of spontaneous cardiac self-repair and regeneration following a direct
      injury.

PMID- 30221789
TI  - Dielectrophoretic separation of microalgae cells in ballast water in a
      microfluidic chip.
AB  - The composition of the ship's ballast water is complex and contains a large
      number of microalgae cells, bacteria, microplastics, and other microparticles. To
      increase the accuracy and efficiency of detection of the microalgae cells in
      ballast water, a new microfluidic chip for continuous separation of microalgae
      cells based on alternating current dielectrophoresis was proposed. In this
      microfluidic chip, one piece of 3-dimensional electrode is embedded on one side
      and eight discrete electrodes are arranged on the other side of the microchannel.
      An insulated triangular structure between electrodes is designed for increasing
      the inhomogeneity of the electric field distribution and enhancing the
      dielectrophoresis (DEP) force. A sheath flow is designed to focus the
      microparticles near the electrode, so as to increase the suffered DEP force and
      improve separation efficiency. To demonstrate the performance of the microfluidic
      separation chip, we developed two species of microalgae cells (Platymonas and
      Closterium) and a kind of microplastics to be used as test samples. Analyses of
      the related parameters and separation experiments by our designed microfluidic
      chip were then conducted. The results show that the presented method can separate
      the microalgae cells from the mixture efficiently, and this is the first time to
      separate two or more species of microalgae cells in a microfluidic chip by using
      negative and positive DEP force simultaneously, and moreover it has some
      advantages including simple operation, high efficiency, low cost, and small size
      and has great potential in on-site pretreatment of ballast water.

PMID- 30221790
TI  - Design and construction of an innovative brain phantom prototype for MRI.
AB  - PURPOSE: The purpose of this project was to construct a physical brain phantom
      for MRI, mimicking structure and T1 relaxation properties of white matter (WM)
      and gray matter (GM). METHODS: The phantom design comprised 2 compartments, 1
      resembling the WM and 1 resembling the GM. Their T1 relaxation times, as assessed
      using an inversion recovery turbo spin echo sequence, were reproduced using an
      agar gel doped with contrast agent (CA) and their folding patterns were simulated
      through a molding-casting procedure using 3D-printed casts and flexible silicone
      molds. Three versions of the assembling procedure were adopted to build: Phantom1
      without any separation; Phantom2 with a varnish layer; and Phantom3 with a thin
      wax layer between the compartments. RESULTS: Phantom1 was characterized by an
      immediate diffusion of CA between the 2 compartments. Phantom2 and Phantom3,
      instead, showed relaxation times and shape comparable with the target ones
      identified in a healthy control subject (WM: 754 +/- 40 ms; GM: 1277 +/- 96 ms).
      Moreover, both compartments revealed intact gyri and sulci. However, the
      diffusion of CA made Phantom2 stable only for a short period of time. Phantom3
      showed stability within a time window of several days but the wax layer between
      the WM and GM was visible in the MRI. CONCLUSION: Structural and intensity
      properties of the constructed phantoms are useful in evaluating and validating
      steps from image acquisition to image processing. Moreover, the described
      constructing procedure and its modular design make it adjustable to a variety of
      applications.

PMID- 30221791
TI  - The relationship between the serotonin 2A receptor gene -1438A/G and 102T/C
      polymorphisms and citalopram/sertraline-induced nausea in major depressed
      patients.
AB  - OBJECTIVE: The aim of the present study was to determine the relationship between
      the polymorphisms of -1438A/G and 102T/C in the 5-HT2A receptor (HTR2A) gene and
      nausea/vomiting as a side effect induced by sertraline (SERT) or citalopram (CIT)
      in patients with major depressive disorder. METHODS: A total of 128 patients were
      enrolled, 63 patients received CIT, whereas 65 patients were treated with SERT.
      Nausea/vomiting were assessed with the UKU Side-effects Rating Scale at baseline
      and at the end of the second and fourth weeks. Polymerase chain reaction
      restriction fragment length polymorphism technique was employed to determine
      genetic differences. RESULTS: We have found that, in the patients treated with
      CIT, there was a nominally significant difference in the genotypic distribution
      associated with -1438A/G polymorphism between patients with and without nausea
      (X2  = 6.15, p = 0.041). Moreover, logistic regression analysis revealed a
      significant association between nausea/vomiting as a side effect and -1438A/G
      polymorphism. That is, patients with the G allele were at a higher risk for
      developing nausea/vomiting (p = 0.044, odds ratio = 2.213). The 102T/C
      polymorphism in the HTR2A gene had no significant effect on the nausea/vomiting
      as a side effect among participants treated with either CIT or SERT. CONCLUSION:
      The present study suggests the association of the HTR2A gene -1438A/G
      polymorphism with nausea/vomiting as a side effect related to CIT treatment.

PMID- 30221793
TI  - Predictors of hospital readmissions in internal medicine patients: Application of
      Andersen's Model.
AB  - OBJECTIVE: This study aimed to identify predictors of internal medicine patients'
      readmission to hospital, using Andersen's behavioral model. METHODS: This
      prospective cohort study included 2622 patients aged >=18 years, who were
      admitted to internal medicine wards at a university hospital between 1 February
      2015 and 31 January 2016. Independent variables were divided into four groups
      (predisposing, enabling, need, and utilization), based on Andersen's model, and
      included in stepwise logistic regression analysis. RESULTS: Younger age, male
      sex, a main diagnosis of neoplasm, longer length of stay, higher comorbidity
      scores, and weaker coping ability predicted all readmission. Predictors of
      unplanned readmission included having someone to help at home following
      discharge, comorbidity scores, and length of stay. Predictors of unplanned,
      related, and preventable readmissions included having someone to help at home
      following discharge, having a regular physician, and the main diagnosis at
      discharge. The most powerful predictors influencing readmission were need-related
      variables. CONCLUSION: Although some predictors of readmission were unalterable,
      they could be used to identify high-risk patients. Innovative approaches
      targeting discharge planning and postdischarge care for patients with high
      comorbidity scores and long length of stay could reduce internal medicine
      patients' unplanned readmission.

PMID- 30221792
TI  - Effect of valacyclovir on EHV-5 viral kinetics in horses with equine multinodular
      pulmonary fibrosis.
AB  - BACKGROUND: Equine herpesvirus-5 is commonly isolated from the lungs of horses
      with EMPF, suggesting an etiological link. Valacyclovir is used empirically to
      treat EMPF; however, no data is available concerning its impact on EHV-5 viral
      kinetics. OBJECTIVES: To determine the effect of oral administration of
      valacyclovir on EHV-5 viral load measured by qPCR in blood, nasal secretions (NS)
      and BALF in horses with EMPF. ANIMALS: Six horses diagnosed with EMPF. METHODS: A
      prospective clinical trial was performed. Horses received 10 days of PO
      administered valacyclovir (loading dose 30 mg/kg, maintenance dose 20 mg/kg).
      Blood, NS, and BALF were collected for EHV-5 viral kinetics analyses during
      treatment. Blood and NS were collected every other day. BALF was collected on day
      0 and day 10. RESULTS: There was no statistical difference in median EHV-5 viral
      load between day 0 and day 10 for all samples tested. In blood median EHV-5 viral
      load was 7676 (range 575-39 781) on day 0 and 6822 (range 1136-18 635)
      glycoprotein B (gB) gene copies per million cells on day 10. For NS median EHV-5
      viral load was 2.944 * 106 (range 184 691-3.394 * 109 ) on day 0 and 8.803 * 106
      (range 251 186-9.868 * 108 ) gB gene copies per million cells on day 10. For BALF
      median EHV-5 viral load was 59,842 (range 61-315 655) on day 0 and 185 083 (range
      3562-542 417) gB gene copies per million cells on day 10. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Valacyclovir might not be an effective short-term antiviral
      treatment but efficacy in treatment of EMPF is unknown.

PMID- 30221794
TI  - Hospital nurse shift length, patient-centered care, and the perceived quality and
      patient safety.
AB  - BACKGROUND: There is no clear evidence that can guide decision makers regarding
      the appropriate shift length in the hospitals in Malaysia. Further, there is no
      study that explored the value of patient-centered care of nurses working longer
      shifts and its impact on the care outcomes. OBJECTIVE: The study aims to
      investigate the effect of the hospital nurse shift length and patient-centered
      care on the perceived quality and safety of nurses in the medical-surgical and
      multidisciplinary wards in Malaysia. METHODS: A cross-sectional survey has been
      conducted on 12 hospitals in Malaysia. Data have been collected via a
      questionnaire. A stratified sampling has been used. The Hayes macro regression
      analyses have been used to examine the mediating effects of patient-centered care
      between the effect of working long shifts on the perceived quality and patient
      safety. RESULTS: There is a significant mediation effect of patient-centered care
      between the effect of shift length on the perceived quality (F = 42.90, P ?
      0.001) and patient safety (F = 25.12, P ? 0.001). CONCLUSION: Patient-centered
      care mitigates the effect of the shift length on the care outcomes. The study
      provides an input for the policymakers that patient-centered care and
      restructuring duty hours are important to provide high-quality patient care.

PMID- 30221796
TI  - Decidualization modulates a signal transduction system via protease-activated
      receptor-1 in endometrial stromal cells.
AB  - PROBLEM: Decidual cells are thought to be involved in the maintenance of
      pregnancy. We conducted this study to evaluate the cellular function of
      endometrial stromal cells (ESCs) transitioning to decidualization. METHODS OF
      STUDY: Normal endometrial specimens were obtained from premenopausal patients who
      had undergone hysterectomies for subserosal leiomyomas. Decidualization of the
      ESCs (DSCs) was induced by incubating subconfluent cells in media containing
      medroxyprogesterone acetate and dibutyryl-cyclic adenosine monophosphate. We
      first analyzed the expression profile of protease-activated receptor-1 (PAR-1)
      between ESCs and DSCs. To investigate the intracellular signal transduction
      system in the DSCs, we incubated cells with thrombin receptor activator peptide 6
      (TRAP-6). The levels of IL-8, monocyte chemo-attractant protein-1, matrix
      metalloproteinase (MMP)-1, and vascular endothelial growth factor in the culture
      medium were measured by enzyme-linked immunosorbent assays. The activation of the
      MAP kinase signaling pathway was detected by a Western blot analysis. The
      activation was evaluated for the expression of p21. RESULTS: PAR-1 receptor
      expression is upregulated in DSCs. The productions of chemokine and MMP-1
      increased in the DSCs with the addition of TRAP-6. The activity of both the ERK-1
      and ERK-2 isoforms was increased by 5-15 minute after TRAP-6 treatment. p70 S6
      kinase showed the strongest expression after 1 hour. p21 was strongly observed in
      ESCs compared to the DSCs. CONCLUSION: Our results suggest that cell function is
      changed by decidualization in association with increasing PAR-1 expression. The
      upregulation of PAR-1 may have some influence on pregnancy in the decidua.

PMID- 30221795
TI  - Effect of common storage temperatures and container types on urine protein :
      creatinine ratios in urine samples of proteinuric dogs.
AB  - BACKGROUND: Preanalytic protein adsorption to polymer and glass container
      surfaces may decrease urine protein concentration measurements and urine protein:
      creatinine ratios (UPC). HYPOTHESIS/OBJECTIVES: Urine stored in PC or glass
      containers will have lower UPC than urine stored in HP containers. The specific
      objective was to determine whether clinically relevant differences in UPC would
      be detected after storage in glass, PC, or HP containers using common storage
      times and temperatures. ANIMALS: Twelve client-owned dogs with proteinuria.
      METHODS: Prospective, nonmasked study, divided into 2 phases. The first phase was
      a pilot study involving multiple (n = 5) measurements at each storage condition
      using 24-hours urine samples from 2 dogs with persistent renal proteinuria of
      different magnitude. The second phase used urine samples from 10 dogs with
      proteinuria of variable magnitude. Sample aliquots were stored in HP, PC, and
      glass containers at 24 degrees C for 4 hours, 4 degrees C for 12 hours, and -20
      degrees C for 72 hours. The UPC of each was measured after storage and compared
      with baseline. RESULTS: Statistically significant but clinically irrelevant
      differences were found in phase 1. In phase 2, storage conditions did not affect
      urinary protein or creatinine concentrations or UPC. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Collection and storage of canine urine samples in clean HP, PC, or
      glass containers at 24 degrees C for 4 hours, 4 degrees C for 12 hours, or -20
      degrees C for 72 hours is unlikely to result in clinically relevant decreases in
      measured UPC values.

PMID- 30221797
TI  - Feasibility, efficacy, and safety of percutaneous MR-guided ablation of small
      (<=12 mm) hepatic malignancies.
AB  - BACKGROUND: Percutaneous tumor ablation is commonly performed using computed
      tomography (CT) or ultrasound (US) guidance, although reliable visualization of
      the target tumor may be challenging. MRI guidance provides more reliable
      visualization of target tumors and allows for real-time imaging and multiplanar
      capabilities, making it the modality of choice, in particular if lesions are
      small. PURPOSE: To investigate the feasibility, technical success, and safety of
      percutaneous MR-guided ablation (RFA n = 27 / MWA n = 16) of small (<=12 mm)
      hepatic malignancies. STUDY TYPE: Retrospective case study. POPULATION: In all,
      45 patients (age: 61.1 +/- 11.8) with hepatic malignancies and a lesion diameter
      of <=12 mm scheduled for percutaneous MR-guided tumor ablation based on a tumor
      board decision were included. FIELD STRENGTH: A 1.5T MR system was used for
      planning, targeting, and monitoring. ASSESSMENT: Feasibility assessment included
      the detection of the target tumor, tumor delineation during MR-fluoroscopy guided
      targeting, and the number of attempts needed for precise applicator placement.
      Technical success was defined as successful performance of the procedure
      including a safety margin of 5 mm. Safety evaluation was based on procedure
      related complications. STATISTICAL TEST: Frequency. RESULTS: Tumor ablation (mean
      diameter 9.0 +/- 2.1 mm) was successfully completed in 43/45 patients. Planning
      imaging was conducted without a contrast agent in 79% (n = 37). In 64% (n = 30),
      the target tumors were visible with MR-fluoroscopy. In six patients (13%),
      planning imaging revealed new, unexpected small lesions, which were either
      treated in the same session (n = 4) or changed therapy management (n = 2) due to
      diffuse tumor progress. Postprocedural imaging revealed a technical success of
      100% (43/43), with no major complications. During follow-up, no local tumor
      progression was observed (mean follow-up 24.7 +/- 14.0 months) although 28% (12)
      patients developed new hepatic lesions distant to the ablation zone. No major
      complications were observed. DATA CONCLUSION: MR-guided ablation is a feasible
      approach for an effective and safe treatment of small hepatic malignancies. LEVEL
      OF EVIDENCE: 4 Technical Efficacy: Stage 4.

PMID- 30221798
TI  - An AB2 -Type Supramolecular Hyperbranched Polymer Based on Pillar[5]arene Host
      Guest Recognition: Construction and Its pH-Responsiveness.
AB  - Supramolecular hyperbranched polymers not only possess the polymeric properties
      of hyperbranched polymers but also obtain additional stimuli-responsiveness due
      to the dynamic properties of non-covalent interactions. Herein, a novel
      supramolecular hyperbranched polymer constructed by an AB2 -type copillar[5]arene
      is reported. NMR spectroscopy, scanning electron microscopy, and viscosity
      experiments are utilized to characterize the self-aggregate process of the AB2
      monomers. Interestingly, the supramolecular hyperbranched polymer exhibits pH
      responsiveness. After protonation of the AB2 monomers by trifluoroacetic acid,
      the binding ability among the monomers becomes stronger, leading to the formation
      of supramolecular hyperbranched polymers with viscosity change. Additionally,
      although no conventional chromophores are doped, the supramolecular hyperbranched
      polymer shows a blue emission under irradiation. The fluorescence can be quenched
      upon addition of trifluoroacetic acid. This study enriches the field of
      supramolecular polymers with new building blocks and architectures and provided a
      new effective method for the fabrication of smart polymer materials with stimuli
      responsiveness and special functions.

PMID- 30221799
TI  - Effects of Sulfide Flavors on AHL-Mediated Quorum Sensing and Biofilm Formation
      of Hafnia alvei.
AB  - : In this study, 10 different sulfide flavor compounds commonly used as food
      additives were screened for antiquorum-sensing activity. Among these, diallyl
      disulfide (DADS) and methyl 2-methyl-3-furyl disulfide (MMFDS) were found to
      exert the strongest inhibition against violacein production in Chromobacterium
      violaceum 026, the tested biosensor strain. DADS and MMFDS also inhibited the
      growth of Hafnia alvei H4, yielding MIC values of 48 and 41.6 mM, respectively.
      In addition, DADS and MMFDS also inhibited the ability of H. alvei H4 to produce
      acyl-homoserine lactone as demonstrated by the reduced level of C6-HSL in the
      supernatant of DADS-treated culture. At concentrations corresponding to 1/4 MIC,
      DADS, and MMFDS inhibited the swarming ability of H. alvei H4 by 73.50% and
      76.43%, respectively, while having virtually no effect on cell growth. The same
      concentrations of DADS and MMFDS also completely inhibited the formation of
      biofilm. These antiquorum sensing effects of DADS and MMFDS involved changes in
      the expression of the quorum-sensing genes luxI and luxR. Quantitative RT-PCR
      analysis showed that the mRNA levels of both genes were significantly reduced by
      DADS and MMDFS at concentrations below their MICs. However, further test using a
      mutant strain of H. alvei lacking luxR (DeltaluxR) revealed significant reduction
      in luxI mRNA level upon treatment of the strain with DADS or MMDFS, but no change
      in luxR mRNA level occurred when a luxI-lacking mutant (DeltaluxI) was treated
      with these compounds. The result therefore suggested that the antiquorum-sensing
      effect of DADS and MMFDS against H. alvei H4 might operate mainly through the
      inhibition of luxI expression in the cells. PRACTICAL APPLICATION: The sulfide
      flavors compounds used in this paper are commonly used in food processing in
      China and are listed in the national standard of Chinese food additives GB2760
      2014. The application of sulfide flavors in food processing can enhance aroma and
      prevent food spoilage.

PMID- 30221800
TI  - Randomized placebo controlled clinical trial of an enteric coated micro-pelleted
      formulation of a pancreatic enzyme supplement in dogs with exocrine pancreatic
      insufficiency.
AB  - BACKGROUND: Pancreatic enzyme supplements for the treatment of exocrine
      pancreatic insufficiency (EPI) in dogs can be uncoated or enteric coated. Enteric
      coated supplements might be advantageous. HYPOTHESIS/OBJECTIVES: Enteric coated
      enzyme supplements are superior to uncoated supplements in dogs with clinical
      EPI. ANIMALS: Eleven dogs with naturally occurring EPI that were apparently free
      from other diseases. METHODS: Randomized, blinded, controlled cross-over clinical
      trial comparing a novel micro-encapsulated enteric coated enzyme supplement to a
      commercially available uncoated product in dogs with clinical EPI. Search of
      serum canine serum trypsin-like immunoreactivity concentration <= 2.5 ug/L in the
      Gastrointestinal Laboratory database was used to identify dogs with EPI. RESULTS:
      There was no difference -4.46% (95% CI: -7.97%--0.96%; P = .15) in the % acid
      hydrolysis fecal fat (primary outcome) between the enteric coated formulation
      (median: 11.8%; range 6.4%-17.0%) and the uncoated pancreatic enzyme replacement
      product (median: 17.5%; range: 5.2%-24.9%) in the 11 dogs that completed the
      study. Other variables did not differ between treatments. CONCLUSIONS AND
      CLINICAL IMPORTANCE: This study, which had low statistical power, did not detect
      a difference between formulations.

PMID- 30221801
TI  - Update on multiparametric MRI of urinary bladder cancer.
AB  - : While many institutions perform MRI during the work-up of urinary bladder
      cancer, others use MRI rarely if at all, possibly due to a variation in the
      reported staging accuracy and unfamiliarity with the potential benefits of
      performing MRI. Through increased application of functional imaging techniques
      including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE)
      imaging, there has been a resurgence of interest regarding evaluation of bladder
      cancer with MRI. Several recent meta-analyses have shown that MRI is accurate at
      differentiating between <=T1 and T2 disease (with pooled sensitivity/specificity
      of ~90/80%) and differentiating between T2 and >=T3 disease. DWI and DCE, in
      combination with high-resolution T2 -weighted images, improves detection and
      possibly local staging accuracy of bladder cancer. High b value echo-planar DWI
      is particularly valuable for tumor detection. Zoomed field of view and segmented
      readout DWI techniques improve image quality by reducing susceptibility artifact,
      while methods to extract calculated high b value images save time and improve the
      contrast-to-noise ratio. DCE traditionally required imaging of the pelvis with
      high temporal but lower spatial resolution; however, advances in parallel and
      keyhole imaging techniques can preserve spatial resolution. The use of compressed
      sensing reconstruction may improve utilization of DCE of the bladder, especially
      when imaging the abdomen simultaneously, as in MR urography. Quantitative imaging
      analysis of bladder cancer using pharmacokinetic modeling of DCE, apparent
      diffusion coefficient values, and texture analysis may enable radiomic assessment
      of bladder cancer grade and stage. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage
      2 J. Magn. Reson. Imaging 2018;48:882-896.

PMID- 30221803
TI  - Neurosurgical Emergencies. By Christopher M. Loftus. New York: Thieme Medical
      Publishers, 2018; 359 pp; $150 (hardcover).

PMID- 30221802
TI  - Polypyridyl-Based Copper Phenanthrene Complexes: A New Type of Stabilized
      Artificial Chemical Nuclease.
AB  - The building of robust and versatile inorganic scaffolds with artificial metallo
      nuclease (AMN) activity is an important goal for bioinorganic, biotechnology, and
      metallodrug research fields. Here, a new type of AMN combining a tris-(2
      pyridylmethyl)amine (TPMA) scaffold with the copper(II) N,N'-phenanthrene
      chemical nuclease core is reported. In designing these complexes, the
      stabilization and flexibility of TPMA together with the prominent chemical
      nuclease activity of copper 1,10-phenanthroline (Phen) were targeted. A second
      aspect was the opportunity to introduce designer phenazine DNA intercalators
      (e.g., dipyridophenazine; DPPZ) for improved DNA recognition. Five compounds of
      formula [Cu(TPMA)(N,N')]2+ (where N,N' is 2,2-bipyridine (Bipy), Phen, 1,10
      phenanthroline-5,6-dione (PD), dipyridoquinoxaline (DPQ), or dipyridophenazine
      (DPPZ)) were developed and characterized by X-ray crystallography. Solution
      stabilities were studied by continuous-wave EPR (cw-EPR), hyperfine sublevel
      correlation (HYSCORE), and Davies electron-nuclear double resonance (ENDOR)
      spectroscopies, which demonstrated preferred geometries in which phenanthrene
      ligands were coordinated to the copper(II) TPMA core. Complexes with Phen, DPQ,
      and DPPZ ligands possessed enhanced DNA binding activity, with DPQ and DPPZ
      compounds showing excellent intercalative effects. These complexes are effective
      AMNs and analysis with spin-trapping scavengers of reactive oxygen species and
      DNA repair enzymes with glycosylase/endonuclease activity demonstrated a
      distinctive DNA oxidation activity compared to classical Sigman- and Fenton-type
      reagents.

PMID- 30221804
TI  - Dependence of c-fos Expression on Amplitude of High-Frequency Spinal Cord
      Stimulation in a Rodent Model.
AB  - OBJECTIVES: Clinical high-frequency spinal cord stimulation (hfSCS) (>250 Hz)
      applied at subperception amplitudes reduces leg and low back pain. This study
      investigates, via labeling for c-fos-a marker of neural activation, whether 500
      Hz hfSCS applied at amplitudes above and below the dorsal column (DC) compound
      action potential (CAP) threshold excites dorsal horn neurons. MATERIALS AND
      METHODS: DC CAP thresholds in rats were determined by applying single biphasic
      pulses of SCS to T12 -T13 segments using pulse widths of 40 or 200 MUsec via a
      ball electrode placed over the left DC and increasing amplitude until a short
      latency CAP was observed on the L5 DC and sciatic nerve. The result of this
      comparison allowed us to substitute sciatic nerve CAP for DC CAP. SCS at T12 -T13
      was applied continuously for two hours using: sham or hfSCS at 500 Hz SCS, 40
      MUsec pulse width, and 50, 70, 90, or 140% CAP threshold. Spinal cord slices from
      T11 -L1 were immunolabeled for c-fos, and the number of c-fos-positive cells was
      quantified. RESULTS: 500 Hz hfSCS applied at 90 and 140% CAP threshold produced
      substantial (>=6 c-fos + neurons on average per slice per segment) c-fos
      expression in more segments between T11 and L1 than did sham stimulation (p <
      0.025, 90% CAP; p < 0.001, 140% CAP, Fisher's Exact Tests) and resulted in more c
      fos-positive neurons on average per slice per segment ipsilateral to than
      contralateral to the SCS electrode at 70, 90, and 140% CAP threshold (p < 0.01,
      Wilcoxon Signed Rank Tests). CONCLUSIONS: The finding of enhanced c-fos
      expression in the ipsilateral superficial dorsal horn provides evidence for
      activation/modulation of neuronal circuitry associated with subperception hfSCS.

PMID- 30221805
TI  - Leveraging technology to identify subclinical deficits in radiologically isolated
      syndrome.

PMID- 30221806
TI  - The GO4KIDDS School Satisfaction Scale.
AB  - BACKGROUND: School experience is an important part of the life of children with
      developmental disabilities (DD) and their families. Research suggests that
      parents of children vary in their level of satisfaction with their child's
      school, but methodology and results have varied and no consistent reliable
      measure of school satisfaction exists. This paper presents a new brief measure of
      school satisfaction along with preliminary information on its psychometric
      properties. METHOD: Parents (n = 185) of children with moderate to severe DD
      completed a longer questionnaire that included the 9-item GO4KIDDS School
      Satisfaction Scale. RESULTS: The GO4KIDDS School Satisfaction Scale demonstrates
      high internal consistency reliability (alpha = 0.93), good item-total
      correlations, and strong correlations with a single-item rating of school
      satisfaction. CONCLUSIONS: Results support reliability and validity, making the
      proposed scale valuable for survey research investigating school satisfaction
      among parents of children with DD.

PMID- 30221807
TI  - Dispersive solid-phase extraction of selected nitrophenols from environmental
      water samples using a zirconium-based amino-tagged metal-organic framework
      nanosorbent.
AB  - This study has centered on the establishment of an efficient, simple and reliable
      dispersive solid-phase extraction method followed by an accurate trace
      determination of selected nitrophenols as a class of compounds with high toxicity
      and low degradability. To achieve the above goal, a zirconium-based amino-tagged
      metal-organic framework nanosorbent was synthesized, characterized and eventually
      employed for the extraction of two nitrophenols from various environmental water
      samples. Once the extraction of analytes had occurred, they were desorbed from
      the metal-organic framework sorbent using an appropriate mixed solvent followed
      by high-performance liquid chromatography with ultraviolet detection. Under the
      optimal extraction conditions, the calibration curves for the analytes were
      linear over the concentration range of 1-200 MUg/L. The accuracy of the method
      was tested by the relative recovery experiments on the fortified real samples
      with the results falling within the range of 91 to 106%, while the corresponding
      precisions varied in the span of 4.6-9.0%. Based on a signal-to-noise ratio of 3,
      the method detection limits were determined to be 0.5 MUg/L for both analytes.

PMID- 30221808
TI  - Imaging Mass Spectrometry of Gold Nanoparticles in a Tissue Section as an
      Immunohistochemical Staining Mass Probe.
AB  - For analysis of low abundance peptides in a tissue section, immunohistochemical
      staining through antibody-antigen interaction is a usual technique. The antibody
      is conjugated with a probe moiety that aids in highly sensitive detection. Gold
      nanoparticles, which show excellent chemical stability and variation of surface
      modifications, are expected to act as a sensitive mass probe to desorb gold ions
      (Au+ , Au2+ , Au3+ ) that are distinguishable from fragment ions from organic
      molecules. Here, green fluorescent proteins (GFP) in a tissue section of a
      transgenic zebrafish was detected by the gold mass probe conjugated with
      antibodies. Due to the efficient ionization and desorption of gold ions, imaging
      mass spectrometry of Au2+ ions indicated the distribution of gold nanoparticles
      stained in a tissue section, and the mass signal distribution was consistent with
      the area where the GFP-expressing cells were distributed. Conventional
      immunofluorescence techniques showed intense autofluorescence that come from
      intrinsic fluorophores in the tissue section. In contrast, the gold nanoparticles
      acted as an immunostaining mass probe that displayed significantly lower
      background signals.

PMID- 30221809
TI  - Electron Transfer Dissociation Mass Spectrometry of Acidic Phosphorylated
      Peptides Cationized with Trivalent Praseodymium.
AB  - The lanthanide ion praseodymium, Pr (III), was employed to study metallated ion
      formation and electron transfer dissociation (ETD) of twenty-seven biological and
      model highly acidic phosphopeptides. All phosphopeptides investigated form
      metallated ions by electrospray ionization (ESI) that can be studied by ETD to
      yield abundant sequence information. The ions formed are [M + Pr - H]2+ , [M +
      Pr]3+ , and [M + Pr + H]4+ . All biological phosphopeptide with a chain length of
      seven or more residues generate [M + Pr]3+ . For biological phosphopeptides, [M +
      Pr]3+ undergoes more backbone cleavage by ETD than [M + Pr - H]2+ and, in some
      cases, full sequence coverage occurs. Acidic model phosphorylated hexa- and octa
      peptides, composed of alanine residues and one phosphorylated residue, form
      exclusively [M + Pr - H]2+ by ESI. Limited sequence information is obtained by
      ETD of [M + Pr - H]2+ with only metallated product ions being generated. For two
      biological phosphopeptides, [M + Pr + H]4+ is observed and may be due to the
      presence of at least one residue with a highly basic side chain that facilitates
      the addition of an extra proton. For the model phosphopeptides, more sequence
      coverage occurs when the phosphorylated residue is in the middle of the sequence
      than at either the N- or C-terminus. ETD of the metallated precursor ions formed
      by ESI generates exclusively metallated and non-metallated c- and z-ions for the
      biological phosphopeptides, while metallated c-, z-ions and a few y-ions form for
      the model phosphopeptides. Most of the product ions contain the phosphorylated
      residue indicating that the metal ion binds predominantly at the deprotonated
      phosphate group. The results of this study indicate that ETD is a promising tool
      for sequencing highly acidic phosphorylated peptides by metal adduction with Pr
      (III) and, by extension, all non-radioactive lanthanide metal ions.

PMID- 30221810
TI  - Controversial issues in vitiligo patients: a review of old and recent treatments.
AB  - Vitiligo is quite a common hypopigmentary disorder, which may affect both
      children and adults with important psychological effects due to the well-known
      leopard skin-like appearance. The authors summarize in the present study the
      published evidence on vitiligo with particular interest on the controversial
      aspects of the disease, such as its definition and the available treatments.

PMID- 30221811
TI  - A sample validation of the Adolescent Stress Questionnaire (ASQ) in New Zealand.
AB  - The Adolescent Stress Questionnaire (ASQ) is a 56-item scale measuring stress in
      10 domains. The scale has been tested in a number of countries worldwide with
      mixed support. The current study tested the factor structure, construct validity,
      and reliability in a sample (n = 1,601) comprising a general population of
      adolescents in New Zealand. Support was found for the 10-factor structure with
      adequate internal consistency as well as strong factorial invariance between male
      and female participants. Significant inverse correlations were found between all
      ASQ domains and both life satisfaction and perceived academic achievement. Most
      ASQ domains revealed gender differences, with female participants reporting
      greater stress than males. Toward a nonbinary perspective of gender, gender
      neutral participants reported greater stress than males and females in certain
      stress domains. Results based on regression analyses indicate that nonacademic
      ASQ domains were generally related to life satisfaction whereas academic ASQ
      domains were related to perceived academic achievement. Positive and negative
      interaction effects were observed between gender and ASQ domains on life
      satisfaction and academic achievement. Overall, the current results indicate that
      the ASQ appears to be a reliable, valid instrument for adolescent stress in New
      Zealand with relevance to perceived life satisfaction and achievement.

PMID- 30221812
TI  - Comparison of the gut microbiota of captive common bottlenose dolphins Tursiops
      truncatus in three aquaria.
AB  - AIMS: This study was conducted to assess the presence and extent of differences
      in the gut microbiota of common bottlenose dolphins depending on rearing
      facilities. METHODS AND RESULTS: Faecal samples were collected from 16 common
      bottlenose dolphins at three aquaria in Japan. After extracting DNA from the
      faeces, the V3-V4 region of bacterial 16S rRNA was amplified and sequenced using
      Illumina MiSeq platform. The constituent phyla of the gut microbiota were similar
      among aquaria; however, the most dominant phylum differed depending on the
      facility, and the compositions of microbiota were remarkably varied at the family
      level among aquaria. The alpha diversity indices tended to differ among aquaria.
      Some bacterial families observed in terrestrial mammalian carnivores or
      carnivorous fish were detected, as well as several bacterial species suspected of
      being pathogenic in dolphins. CONCLUSION: Our findings indicate that captive
      environmental conditions including prey and housing types may contribute to
      differences in the gut microbiota of the dolphins. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This is the first study revealing the differences in gut microbiota of
      captive dolphins among facilities. Our findings will provide valuable information
      for improving the health management of dolphins.

PMID- 30221813
TI  - The role of dietitians in residential aged care: How do cooks and chefs perceive
      their contribution?
AB  - OBJECTIVE: This study aimed to explore how dietitians could work with cooks and
      chefs to contribute to best practice. METHODS: Data from interviews and focus
      groups comprising 38 chefs, cooks and food service managers were analysed.
      Inductive line-by-line coding of transcripts was conducted within a critical
      realist framework. Coding was completed independently by two authors before
      reaching consensus on themes. RESULTS: Four main themes emerged: (i) knowledge
      sharing; (ii) communication; (iii) collaboration; and (iv) accessibility.
      Participants praised dietitians' knowledge and expertise, but some raised
      concerns about inconsistency in the advice they received. CONCLUSION: Dietitians
      working in residential aged care are ideally positioned to act as advocates for
      residents and food services. However, findings suggest that experiences of
      working with dietitians are mixed. Aged care menu guidelines and quality measures
      could assist, not only in promoting a consistent approach to dietetic advice, but
      also a system for benchmarking satisfaction and best practice.

PMID- 30221814
TI  - The evolution of selector gene function: Expression dynamics and regulatory
      interactions of tiptop/teashirt across Arthropoda.
AB  - The transcription factors spineless (ss) and tiptop/teashirt (tio/tsh) have been
      shown to be selectors of distal appendage identity in an insect, but it is
      unknown how they regulate one another. Here, we examined the regulatory
      relationships between these two determinants in the milkweed bug Oncopeltus
      faciatus, using maternal RNA interference (RNAi). We show that Ofas-ss RNAi
      embryos bear distally transformed antennal buds with heterogeneous Ofas-tio/tsh
      expression domains comparable to wild type legs. In the reciprocal experiment,
      Ofas-tio/tsh RNAi embryos bear distally transformed walking limb buds with
      ectopic expression of Ofas-ss in the distal leg primordia. These data suggest
      that Ofas-ss is required for the maintenance of Ofas-tio/tsh expression in the
      distal antenna, whereas Ofas-tio/tsh represses Ofas-ss in the leg primordia. To
      assess whether expression boundaries of tio/tsh are associated with the trunk
      region more generally, we surveyed the expression of one myriapod and two
      chelicerate tio/tsh homologs. Our expression survey suggests that tio/tsh could
      play a role in specifying distal appendage identity across Arthropoda, but Hox
      regulation of tio/tsh homologs has been evolutionarily labile.

PMID- 30221815
TI  - Intravenous immunoglobulin for treatment of necrobiotic xanthogranuloma.

PMID- 30221816
TI  - Probing Polymer Chain Conformation and Fibril Formation of Peptide Conjugates.
AB  - Covalent conjugates between a synthetic polymer and a peptide hormone were used
      to probe the molecular extension of these macromolecules and how the polymer
      modifies the fibril formation of the hormone. NMR spectroscopy of 15 N labeled
      parathyroid hormone (PTH) was employed to visualize the conformation of the
      conjugated synthetic polymer, triggered by small temperature changes via its
      lower critical solution temperature. A shroud-like polymer conformation dominated
      the molecular architecture of the conjugated chimeras. PTH readily forms amyloid
      fibrils, which is probably the physiological storage form of the hormone. The
      polyacrylate based polymers stimulated the nucleation processes of the peptide.

PMID- 30221817
TI  - Risk factors for infection after pediatric lung transplantation.
AB  - Although infection is the leading cause of death in the first year following
      pediatric lung transplantation, there are limited data on risk factors for early
      infection. Sepsis remains under-recognized and under-reported in the early post
      operative period for lung transplant recipients (LTR). We evaluated the incidence
      of infection and sepsis, and identified risk factors for infection in the early
      post-operative period in pediatric LTRs. A retrospective review of medical
      records of LTRs at a large quaternary-care hospital from January 2009 to March
      2016 was conducted. Microbiology results on days 0-7 after transplant were
      obtained. Sepsis was defined using the 2005 International Pediatric Consensus
      Conferencecriteria. Risk factors included history of recipient and donor
      infection, history of multi-drug resistant (MDR) infection, nutritional status,
      and surgical times. Among the 98 LTRs, there were 22 (22%) with post-operative
      infection. Prolonged donor ischemic time >=7 hours, cardiopulmonary bypass(CPB)
      time >=340 minutes, history of MDR infection and diagnosis of cystic fibrosis
      were significantly associated with infection. With multivariable regression
      analysis, only prolonged donor ischemic time remained significant (OR 4.4, 95%
      CI: 1.34-14.48). Further research is needed to determine whether processes to
      reduce donor ischemic time could result in decreased post-transplant morbidity.

PMID- 30221818
TI  - The effectiveness of magnetic stimulation for patients with pelvic floor
      dysfunction: A systematic review and meta-analysis.
AB  - AIMS: To evaluate the value of magnetic stimulation (MS) in patients with pelvic
      floor dysfunction (PFD). METHODS: The Preferred Reporting Items for Systematic
      Review and Meta-analysis (PRISMA) statement was followed. We searched five
      databases for articles published until November 2017. Included studies
      investigated the effects of MS on PFD. Meta-analysis of RCTs was performed using
      a random effects model, and narrative analysis was undertaken where meta-analysis
      was not possible. RESULTS: A total of 20 studies including 1019 patients were
      eligible for inclusion whose level of evidence for the included studies was low.
      Meta-analysis of four trials comparing MS with sham intervention showed that MS
      was not associated with significant improvement in ICIQ-SF score (-0.52, 95%CI 
      1.05, 0.01; P = 0.06, I2  = 16%), QOL score (-0.27, 95%CI -0.57, 0.04; P = 0.09,
      I2  = 0%), number of leakages (-0.16, 95%CI -0.62, 0.29; P = 0.48, I2  = 52%),
      and pad test (-1.36, 95%CI -2.64, -0.08; P = 0.04, I2  = 94%). Narrative review
      showed that there were no convincing evidences that MS was effective for chronic
      pelvic floor pain, detrusor overactivity, overactive bladder, and the included
      RCTs had controversial results. MS may have some benefits for nocturnal enuresis
      and erectile dysfunction according to the trials. CONCLUSIONS: There is no
      convinced evidence to support the benefits of using MS in the management of PFD.
      The applicability of MS in the treatment of PFD remains uncertain, so larger,
      well-designed trials with longer follow-up periods adopted relevant and
      comparable outcomes are needed to be further explored to provide a definitive
      conclusion.

PMID- 30221819
TI  - Development of hidradenitis suppurativa in a patient treated with ustekinumab for
      her psoriasis: A potential paradoxical reaction?

PMID- 30221820
TI  - Bacterial infections in pediatric patients during early post liver transplant
      period: A prospective study in Iran.
AB  - BACKGROUND: Bacterial infection in early period after liver transplant (LT) is
      the main cause of morbidity and mortality; however, data on children is limited.
      METHODS: To investigate the frequency, characteristics, and the associated
      factors of bacterial infection during hospitalization after LT, we prospectively
      enrolled all consecutive children with LT for a one-year, case-control study at
      the unique referral center of pediatric LT in Iran. RESULTS: Eighty-five events
      of bacterial infection were detected among 51 out of 94 LT recipients (54.3%)
      (infection group). Forty-three patients without bacterial infection constituted
      the control group. The frequency of bacterial infection based on the 51
      microbiologically documented events was 31.9% (30 out of 94 patients). Major site
      of bacterial isolation were abdomen (43.6%). The following variables were
      associated with bacterial infection in univariate analysis: younger age (5.6 vs
      8.9 years old), longer duration of JP Drain (13.4 vs 6.3 days), central venous
      catheter (14.6 vs 7.6 days), and Foley catheter insertion (7.3 vs 4.5 days),
      reoperation (57% vs 12% of patients), mean frequency of reoperation (1.1 vs 0.1
      times), and intensive care unit stay (12.1 vs 6.5 days). In multivariate
      analysis, only longer hospital stay after transplant (23.6 vs 10.9 days) was
      independently associated with bacterial infection. All ten deaths occurred within
      the infection group and half of which directly caused by infection. CONCLUSIONS:
      These infections were associated with longer hospital stay and higher mortality
      rate. Conducting further studies with larger sample size and investigating more
      effective prophylactic measures should be considered in future studies.

PMID- 30221821
TI  - Biphasic amyloidosis involved in the face: Effective treatment with 30% salicylic
      acid.

PMID- 30221822
TI  - Family environment and traumatic dental injuries in adolescents.
AB  - BACKGROUND/AIMS: No comprehensive assessment of the influence of the home
      environment on traumatic dental injuries (TDI) has been conducted to date. The
      aim of this study was to explore the relationship between family environment and
      TDI among adolescents from East London. MATERIALS AND METHODS: This cross
      sectional study used data from 646 adolescents who participated in phase III of
      the Research with East London Adolescents Community Health Survey (RELACHS).
      Family environment was measured with four indicators (non-nuclear family,
      discordant parental relationship and levels of parental support and parental
      punishment) measured through a self-administered questionnaire. Clinical
      examinations were performed for TDI, overjet and lip coverage. Logistic
      regression was used to test the crude and adjusted (controlling for
      sociodemographic and clinical factors) association of each family environment
      characteristic with TDI prevalence. RESULTS: Twenty-nine percent of adolescents
      were from non-nuclear families, and 52.3% reported a discordant parental
      relationship. The mean score for parental support was -0.01 (SD: 0.90, range: 
      0.11 to 0.08), and the mean parental punishment score was 0.03 (SD: 0.86, range: 
      0.04 to 0.10). Adolescents from non-nuclear families had 1.63 (95% confidence
      interval: 1.06-2.53) greater odds of having TDI than those from nuclear families.
      However, this association was fully attenuated after adjusting for
      sociodemographic and clinical factors. The other three indicators of family
      environment were not associated with TDI either in crude or adjusted regression
      models. CONCLUSION: This study found weak evidence of an association between
      family environment and TDI.

PMID- 30221823
TI  - Promoting Terminal Olefin Metathesis with a Supported Cationic Molybdenum Imido
      Alkylidene N-Heterocyclic Carbene Catalyst.
AB  - Silica-supported cationic Mo-imido alkylidene N-heterocyclic carbene catalysts,
      prepared by surface organometallic chemistry, display contrasting olefin
      metathesis activity for terminal and internal olefins. The high metathesis
      activity towards terminal alkenes is attributed to the strong sigma-donating
      property of the NHC ancillary ligand, which disfavors the formation of the parent
      square-planar metallacyclobutane, an off-cycle reaction intermediate resulting
      from the reaction with ethylene, one of the metathesis products. This tailored
      ligand environment also allowed the first trigonal bipyramidal (TBP)
      metallacyclobutane reaction intermediate for supported Mo metathesis catalysts to
      be identified.

PMID- 30221824
TI  - The Nurse-Engineer: A New Role to Improve Nurse Technology Interface and Patient
      Care Device Innovations.
AB  - PURPOSE: The purpose of this article is to describe two innovative biomedical
      engineering and nursing collaborations designed to educate a new cadre of
      professionals and develop new knowledge and innovations (robots, patient care
      devices, and computer simulation). ORGANIZING CONSTRUCT: Complex health problems
      demand a highly skilled response that uses teams of professionals from various
      disciplines. When the biomedical engineering lens is expanded to include the
      practical perspective of nursing, opportunities emerge for greater technology
      nurse interface and subsequent innovation. A joint nursing-engineering degree
      program provides the ideal preparation for a well-informed nurse-engineer who can
      explore new and innovative solutions that will improve care and patient outcomes.
      APPROACH: A review of the literature provides the background on innovation and
      engineering in nursing and a rationale for the development of two innovative
      joint degrees, as well as a description of those programs. FINDINGS: These
      innovative programs will advance healthcare-related technology and maximize the
      potential contribution of the nursing profession in the design and implementation
      of creative solutions. They also have the potential to increase the skills and
      knowledge for students enrolled in biomedical engineering or Bachelor of Science
      in nursing programs individually, providing them with interdisciplinary training
      and exposure. CLINICAL RELEVANCE: Important patient care improvement
      opportunities are missed when nurses are not actively engaged in patient care
      device innovation and creation. Innovative nurse and engineer collaborations are
      needed in various forms to leverage nurse ingenuity and create patient care
      innovations.

PMID- 30221825
TI  - Evaluation of multidisciplinary pulmonary rehabilitation education delivered by
      either DVD or spoken talk.
AB  - INTRODUCTION: Pulmonary rehabilitation (PR) is a multidisciplinary program of
      care for patients with chronic respiratory disease. The educational component is
      an integral component and represents a large proportion of a program. However, it
      can be difficult to secure regular multidisciplinary input to PR programs.
      OBJECTIVES: This service evaluation assessed whether DVD presentations are
      acceptable to patients and effective as an education medium. METHOD: Two PR
      groups were compared; one group received education by DVD and the other by spoken
      talk. Both groups evaluated the content and delivery of each session and their
      knowledge was measured using the Bristol COPD Knowledge Questionnaire (BCKQ).
      RESULTS: One hundred and twenty-three patients with Chronic Obstructive Pulmonary
      Disease (COPD) took part; 58 evaluated the DVD, 75 the talk sessions. There were
      no differences between the two groups at baseline with respect to age, gender
      distribution, or FEV1 . Both groups were satisfied with the content (99.46% DVD,
      100% talk group) and delivery (100% both DVD and talk groups) of their education
      sessions. At baseline, there were no between group differences in the mean BCKQ.
      After PR, significant changes in BCKQ scores were seen within the groups (6.52
      points (1.48-11.37) DVD group and 8.96 points (6.50-11.19) talk group), again
      with no differences between the groups. CONCLUSION: A DVD-based education package
      is both acceptable to PR patients and effective at improving patients' knowledge
      of COPD. Using filmed educational talks with PR would have a number of benefits
      to both the patients and the service and may be a way of increasing the capacity
      of PR services.

PMID- 30221826
TI  - Dimethylammonium Incorporation in Lead Acetate Based MAPbI3 Perovskite Solar
      Cells.
AB  - Over the last years, several different pathways have been suggested for producing
      perovskite thin films for solar cell applications. While the merit of these
      methods with respect to the solar cell efficiency have been shown, the actual
      composition of the resulting thin films is often not investigated. Here, we show
      that methylammonium lead iodide films produced using lead acetate as a lead
      source can have up to 15 % dimethylammonium incorporated into their crystal
      structure, even though this ion is often consider to be too large for
      incorporation. The origin of this ion lies in the precursor solution, where it is
      formed in a reaction that is facilitated by the basic character of the acetate
      ions. We further show that these dimethylammonium ions are incorporated in a
      random fashion throughout the crystal structure, owing to the lack of observable
      ordered domains.

PMID- 30221827
TI  - Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic
      Target Attainment Across Adult Indications and Patient Subgroups.
AB  - Ceftazidime-avibactam is a novel beta-lactam/beta-lactamase inhibitor combination
      for the treatment of serious infections caused by resistant gram-negative
      pathogens. Population pharmacokinetic (PopPK) models were built to incorporate
      pharmacokinetic (PK) data from five phase III trials in patients with complicated
      intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), or
      nosocomial (including ventilator-associated) pneumonia. Ceftazidime and avibactam
      pharmacokinetics were well-described by two-compartment disposition models, with
      creatinine clearance (CrCL) the key covariate determining clearance variability.
      Steady-state ceftazidime and avibactam exposure for most patient subgroups
      differed by <= 20% vs. healthy volunteers. Probability of PK/pharmacodynamic (PD)
      target attainment (free plasma ceftazidime > 8 mg/L and avibactam > 1 mg/L for >=
      50% of dosing interval) was >= 94.9% in simulations for all patient subgroups,
      including indication and renal function categories. No exposure-microbiological
      response relationship was identified because target exposures were achieved in
      almost all patients. These modeling results support the approved ceftazidime
      avibactam dosage regimens (2000-500 mg every 8 hours, adjusted for CrCL <= 50
      mL/min).

PMID- 30221828
TI  - Combining Butyrated ManNAc with Glycoengineered CHO Cells Improves EPO Glycan
      Quality and Production.
AB  - Sodium butyrate (NaBu) is not only well-known for enhancing protein production,
      but also degrades glycan quality. In this study, butyrate supplied by the
      precursor molecule 1,3,4-O-Bu3 ManNAc is applied to overcome the negative effects
      of NaBu on glycan quality while simultaneously increasing the productivity of the
      model recombinant erythropoietin (EPO). The beneficial impact of 1,3,4-O-Bu3
      ManNAc on EPO glycan quality, while evident in wild-type CHO cells, is
      particularly pronounced in glycoengineered CHO cells with stable overexpression
      of beta-1,4- and beta-1,6-N-acetylglucosaminyltransferases (GnTIV and GnTV) and
      alpha-2,6-sialyltransferase (ST6) enzymes responsible for N-glycan antennarity
      and sialylation. Supplementation of 1,3,4-O-Bu3 ManNAc achieves approximately 30%
      sialylation enhancement on EPO protein in wild-type CHO cells. Overexpression of
      GnTIV/GnTV/ST6 in CHO cells increases EPO sialylation about 40%. Combining 1,3,4
      O-Bu3 ManNAc treatment in glyocengineered CHO cells promotes EPO sialylation
      about 75% relative to EPO from wild-type CHO cells. Moreover, a detailed mass
      spectrometric ESI-LC-MS/MS characterization of glycans at each of the three N
      glycosylation sites of EPO showed that the 1st N-site is highly sialylated and
      either the negative impact of NaBu or the beneficial effect 1,3,4-O-Bu3 ManNAc
      treatments mainly affects the 2nd and 3rd N-glycan sites of EPO protein. In
      summary, these results demonstrate 1,3,4-O-Bu3 ManNAc can compensate for the
      negative effect of NaBu on EPO glycan quality while simultaneously enhancing
      recombinant protein yields. In this way, a platform that integrates
      glycoengineering with metabolic supplementation can result in synergistic
      improvements in both production and glycosylation in CHO cells.

PMID- 30221829
TI  - Incorporating 4D into Bioprinting: Real-Time Magnetically Directed Collagen Fiber
      Alignment for Generating Complex Multilayered Tissues.
AB  - In vitro multilayered tissues with mimetic architectures resembling native
      tissues are valuable tools for application in medical research. In this study, an
      advanced bioprinting strategy is presented for aligning collagen fibers contained
      in functional bioinks. Streptavidin-coated iron nanoparticles are embedded in
      printable bioinks with varying concentrations of low gelling temperature agarose
      and type I collagen. By applying a straightforward magnetic-based mechanism in
      hydrogels during bioprinting, it is possible to align collagen fibers in less
      concentrated hydrogel blends with a maximum agarose concentration of 0.5 w/v%.
      Conversely, more elevated concentrations of agarose in printable blends show
      random collagen fiber distribution. Interestingly, hydrogel blends with
      unidirectionally aligned collagen fibers show significantly higher compression
      moduli compared to hydrogel blends including random fibers. Considering its
      application in the field of cartilage tissue engineering, bioprinted constructs
      with alternating layers of aligned and random fibers are fabricated. After 21
      days of culture, cell-loaded constructs with alternating layers of aligned and
      random fibers express markedly more collagen II in comparison to solely randomly
      oriented fiber constructs. These encouraging results translate the importance of
      the structure and architecture of bioinks used in bioprinting in light of their
      use for tissue engineering and personalized medical applications.

PMID- 30221830
TI  - Four days of bed rest increases intrinsic mitochondrial respiratory capacity in
      young healthy males.
AB  - Bed rest leads to impaired glucose tolerance. Whether this is linked to
      maladaptation's in skeletal muscle mitochondrial function and in particular to
      the level of reactive oxygen species (ROS) is at present unknown. The aim of this
      longitudinal study was to quantify skeletal muscle mitochondrial function
      (respiratory capacity and ROS production) together with glucose tolerance after 4
      days of strict bed rest in healthy young male subjects (n = 14). Mitochondrial
      function was determined in permeabilized muscle fibers using high-resolution
      respirometry and fluorometry, mitochondrial content (citrate synthase [CS]
      activity) and antioxidant protein expression levels were assessed in parallel to
      this. Glucose tolerance was determined by means of oral glucose tolerance tests.
      Intrinsic mitochondrial respiratory capacity was augmented after the bed rest
      period (CI + IIP : 0.43 +/- 0.12 vs. 0.55 +/- 0.14 [pmol/sec/mg]/CS activity),
      due to a decreased CS activity (158 +/- 39 vs. 129 +/- 25 mU/mg dw.). No
      differences were observed in ROS production (per mg of tissue or when normalized
      to CS activity). Furthermore, the protein content for catalase was increased
      while superoxide dismutase and glutathione peroxidase remained unaffected. These
      findings were accompanied by an impaired glucose tolerance after the bed rest
      period (Matsuda index: 12 +/- 6 vs. 9 +/- 5). The change in intrinsic
      mitochondrial respiratory capacity could be an early indication in the
      development of impaired glucose tolerance. The increased catalase protein content
      might explain that no change was seen in ROS production after 4 days of bed rest.
      Whether these findings can be extrapolated to lifestyle-dependent decrements in
      physical activity and the development of type-2-diabetes remains unknown.

PMID- 30221832
TI  - Enzymatic Adaptation of Podospora anserina to Different Plant Biomass Provides
      Leads to Optimized Commercial Enzyme Cocktails.
AB  - As a late colonizer of herbivore dung, Podospora anserina has evolved an
      enzymatic machinery to degrade the more recalcitrant fraction of plant biomass,
      suggesting a great potential for biotechnology applications. The authors
      investigated its transcriptome during growth on two industrial feedstocks,
      soybean hulls (SBH) and corn stover (CS). Initially, CS and SBH results in the
      expression of hemicellulolytic and amylolytic genes, respectively, while at later
      time points a more diverse gene set is induced, especially for SBH. Substrate
      adaptation is also observed for carbon catabolism. Overall, SBH resulted in a
      larger diversity of expressed genes, confirming previous proteomics studies. The
      results not only provide an in depth view on the transcriptomic adaptation of P.
      anserina to substrate composition, but also point out strategies to improve
      saccharification of plant biomass at the industrial level.

PMID- 30221831
TI  - Fast-food meal reduces peripheral artery endothelial function but not cerebral
      vascular hypercapnic reactivity in healthy young men.
AB  - Consumption of a representative fast-food meal (FFMeal) acutely impairs
      peripheral conduit artery vascular function; however, the effect on cerebral
      vascular function remains unknown. This study tested the hypothesis that a FFMeal
      would impair cerebral vascular function as indexed by an attenuated increase in
      cerebral vascular conductance (CVCI) in the middle cerebral artery (MCA) during a
      hypercapnic challenge. Ten healthy men (age: 24 +/- 3 years, BMI: 24.3 +/- 3.8
      kg/m2 ) were studied under two conditions; a standardized FFMeal (990 kcals, 50%
      fat, 36% carbohydrate, 14% protein, and 2120 mg sodium) and a fasting control
      condition. Basal hemodynamics, cerebral vasomotor reactivity (CVMR), and brachial
      artery flow-mediated dilation (BA FMD) were completed after an overnight fast
      (Pre) and again 2 h and 4 h later both days. To assess CVMR, subjects rebreathed
      from a 5-L bag while MCA velocity (MCAVmean ) was measured using transcranial
      Doppler (TCD) ultrasound and converted into CVCI (MCAVmean /mean arterial
      pressure). Peripheral artery endothelial function was assessed via BA FMD
      following a standard 5-min occlusion protocol. As expected, BA FMD was reduced at
      2 h (Pre: 6.6 +/- 1.7% vs. 5.2 +/- 1.8%, P = 0.01). However, despite significant
      impairment in BA FMD, neither peak CVCI%baseline nor CVMR was affected by the
      FFMeal (Control-Pre: 1.9 +/- 1.1, 2 h: 2.1 +/- 1.1, 4 h: 1.7 +/- 1.1 ?CVCI%.?PET
      CO2-1 vs. FFMeal-Pre: 2.1 +/- 1.1, 2 h: 2.2 +/- 0.7, 4 h: 1.9 +/- 0.9 ?CVCI%.?PET
      CO2-1 , time * condition P = 0.88). These results suggest that cerebral vascular
      reactivity to hypercapnia in healthy young men is not altered by an acute FFMeal.

PMID- 30221834
TI  - Hydrogen-Generating Ru/Pt Bimetallic Photocatalysts Based on Phenyl
      Phenanthroline Peripheral Ligands.
AB  - Recent studies on hydrogen-generating supramolecular bimetallic photocatalysts
      indicate a more important role of the peripheral ligands than expected,
      motivating us to design a Ru/Pt complex with 4,7-diphenyl-1,10-phenanthroline
      peripheral ligands. Photoinduced intra- and inter-ligand internal conversion
      processes have been investigated using transient absorption spectroscopy,
      spanning the femto- to nanosecond timescale. After photoexcitation and ultrafast
      intersystem crossing, triplet states localised on either the peripheral ligands
      or on the bridging ligand/catalytic unit are populated in a non-equilibrated way.
      Time-resolved photoluminescence demonstrates that the lifetime for the Ru/Pt
      dinuclear species (795+/-8 ns) is significantly less than that of the mononuclear
      analogue (1375+/-20 ns). The photocatalytic studies show modest hydrogen turnover
      numbers, which is possibly caused by the absence of an excited state equilibrium.
      Finally, we identify challenges that must be overcome to further develop this
      class of photocatalysts and propose directions for future research.

PMID- 30221833
TI  - Effect of leg immersion in mild warm carbonated water on skin and muscle blood
      flow.
AB  - Leg immersion in carbonated water improves endothelial-mediated vasodilator
      function and decreases arterial stiffness but the mechanism underlying this
      effect remains poorly defined. We hypothesized that carbonated water immersion
      increases muscle blood flow. To test this hypothesis, 10 men (age 21 +/- 0 years;
      mean +/- SD) underwent lower leg immersion in tap or carbonated water at 38
      degrees C. We evaluated gastrocnemius muscle oxyhemoglobin concentration and
      tissue oxygenation index using near-infrared spectroscopy, skin blood flow by
      laser Doppler flowmetry, and popliteal artery (PA) blood flow by duplex
      ultrasound. Immersion in carbonated, but not tap water elevated PA (from 38 +/-
      14 to 83 +/- 31 mL/min; P < 0.001) and skin blood flow (by 779 +/- 312%, P <
      0.001). In contrast, lower leg immersion elevated oxyhemoglobin concentration and
      tissue oxygenation index with no effect of carbonation (P = 0.529 and P = 0.495).
      In addition, the change in PA blood flow in response to immersion in carbonated
      water correlated with those of skin blood flow (P = 0.005) but not oxyhemoglobin
      concentration (P = 0.765) and tissue oxygenation index (P = 0.136) while no
      relations was found for tap water immersion. These findings indicate that water
      carbonation has minimal effect on muscle blood flow. Furthermore, PA blood flow
      increases in response to lower leg immersion in carbonated water likely due to a
      large increase in skin blood flow.

PMID- 30221836
TI  - Detrimental Effect of Sintering Additives on Conducting Ceramics: Yttrium-Doped
      Barium Zirconate.
AB  - Y-doped BaZrO3 (BZY) is currently the most promising proton-conductive ceramic
      type electrolyte for application in electrochemical devices, including fuel cells
      and electrolyzer cells. However, owing to its refractory nature, sintering
      additives, such as NiO, CuO, or ZnO are commonly added to reduce its high
      sintering temperature from 1600  degrees C to approximately 1400  degrees C. Even
      without deliberately adding a sintering additive, the NiO anode substrate
      provides another source of the sintering additive; during the co-sintering
      process, NiO diffuses from the anode into the BZY electrolyte layer. In this
      work, a systematic study of the effect of NiO, CuO, and ZnO on the
      electroconductive properties of BaZr0.8 Y0.2 O3-delta (BZY20) is conducted. The
      results revealed that the addition of NiO, CuO, or ZnO into BZY20 not only
      degraded the electrical conductivity but also resulted in enhancement of the hole
      conduction. Removal of these sintering additives can be realized by post
      annealing in hydrogen at a mild temperature of 700  degrees C, but it is
      kinetically very slow. Therefore, the addition of NiO, CuO, and ZnO is
      detrimental to the electroconductive properties of BZY20, and significantly
      restrict its application as an electrolyte. The development of new sintering
      additives, new anode catalysts, or new methods for preparing BZY electrolyte
      based cells is urgently needed.

PMID- 30221835
TI  - Move to Nano-Arthrology: Targeted Stimuli-Responsive Nanomedicines Combat
      Adaptive Treatment Tolerance (ATT) of Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) is one of the most popular chronic autoimmune diseases
      characterized with persistent synovial inflammation and bone destruction.
      Although considerable developments have been gained in clinical treatment of RA,
      the major drawback to RA therapy stems from the adaptive treatment tolerance
      (ATT) following the long-term drug use, which causes compromised efficacy,
      sustained drug dose increase, and severe adverse events. To address these
      challenges, it is of great significance to put forward innovative therapeutic
      approaches for RA treatment. Nowadays, developments of nanotechnology-based
      nanomedicines (NMs) for RA are in progress. Multifunctional NMs with targeted
      stimuli-responsive features have been one of the central concepts in designing
      more accessible formulations for efficient RA treatment. These NMs are able to
      postpone RA progression effectively, because of their delivery and on-demand
      release of medicaments at targeted sites in response to external or internal
      stimuli related to the RA pathophysiology without obvious adverse side-effects on
      the normal tissues. Therefore, NMs have gained interest from pre-clinical
      research scientists as well as clinical doctors worldwide. Herein, the authors
      highlight the recent attempts of targeted stimuli-responsive NMs for RA therapy
      in the last 5 years. The described progresses may pave the way to novel and
      highly effective RA NMs.

PMID- 30221838
TI  - Standard abbreviations.

PMID- 30221837
TI  - Advances and Future Perspectives in 4D Bioprinting.
AB  - Three-dimensionally printed constructs are static and do not recapitulate the
      dynamic nature of tissues. Four-dimensional (4D) bioprinting has emerged to
      include conformational changes in printed structures in a predetermined fashion
      using stimuli-responsive biomaterials and/or cells. The ability to make such
      dynamic constructs would enable an individual to fabricate tissue structures that
      can undergo morphological changes. Furthermore, other fields (bioactuation,
      biorobotics, and biosensing) will benefit from developments in 4D bioprinting.
      Here, the authors discuss stimuli-responsive biomaterials as potential bioinks
      for 4D bioprinting. Natural cell forces can also be incorporated into 4D
      bioprinted structures. The authors introduce mathematical modeling to predict the
      transition and final state of 4D printed constructs. Different potential
      applications of 4D bioprinting are also described. Finally, the authors highlight
      future perspectives for this emerging technology in biomedicine.

PMID- 30221839
TI  - High-intensity interval training changes mitochondrial respiratory capacity
      differently in adipose tissue and skeletal muscle.
AB  - The effect of high-intensity training (HIT) on mitochondrial ADP sensitivity and
      respiratory capacity was investigated in human skeletal muscle and subcutaneous
      adipose tissue (SAT). Twelve men and women underwent 6 weeks of HIT (7 * 1 min at
      app. 100% of maximal oxygen uptake (VO2max )). Mitochondrial respiration was
      measured in permeabilized muscle fibers and in abdominal SAT. Mitochondrial ADP
      sensitivity was determined using Michaelis Menten enzyme kinetics. VO2max , body
      composition and citrate synthase (CS) activity (skeletal muscle) and mtDNA (SAT)
      were measured before and after training. VO2max increased from 2.6 +/- 0.2 to 2.8
      +/- 0.2 L O2 /min (P = 0.011) accompanied by a decreased mitochondrial ADP
      sensitivity in skeletal muscle (Km : 0.14 +/- 0.02 to 0.29 +/- 0.03 mmol/L ADP (P
      = 0.002)), with no changes in SAT (Km : 0.12 +/- 0.02 to 0.16 +/- 0.05 mmol/L
      ADP; P = 0.186), following training. Mitochondrial respiratory capacity increased
      in skeletal muscle from 57 +/- 4 to 67 +/- 4 pmol O2 .mg-1 .sec-1 (P < 0.001),
      but decreased with training in SAT from 1.3 +/- 0.1 to 1.0 +/- 0.1 pmol O2 .mg-1
      .sec-1 (P < 0.001). CS activity increased (P = 0.027) and mtDNA was unchanged
      following training. Intrinsic mitochondrial respiratory capacity was unchanged in
      skeletal muscle, but increased in SAT after HIT. In summary, our results
      demonstrate that mitochondrial adaptations to HIT in skeletal muscle are
      comparable to adaptations to endurance training, with an increased mitochondrial
      respiratory capacity and CS activity. However, mitochondria in SAT adapts
      differently compared to skeletal muscle mitochondria, where mitochondrial
      respiratory capacity decreased and mtDNA remained unchanged after HIT.

PMID- 30221841
TI  - Adverse Events and Resource Use Before and After Treat to Target in Rheumatoid
      Arthritis:A Post-Hoc Analysis of a Randomized Controlled Trial.
AB  - INTRODUCTION: Treat to target (TTT) is an accepted paradigm for care of patients
      with rheumatoid arthritis (RA). Since TTT can be associated with more medication
      switches, concerns arise whether implementing TTT may increase adverse events
      and/or resource use. METHODS: We used data from six practices enrolled in an 18
      month cluster-randomized controlled trial to compare adverse events and resource
      use before (months 1-9) and during (months 10-18) a TTT intervention. The
      outcomes of interest, adverse events and resource use, were based on medical
      record review of all rheumatology visits for RA patients before and during the
      intervention. RESULTS: We examined records for 321 patients before the
      intervention and 315 during the intervention. An adverse event was recorded in
      10.2% of visits before the intervention and 8.8% during the intervention (P =
      0.41). Biologic DMARDs were used in 53.6% of patients before the intervention and
      49.8% during the intervention (p = 0.73). Rheumatology visits were more frequent
      before the intervention (mean 4.0 +/- 1.4) than during the intervention (mean 3.6
      +/- 1.2; p = 0.02). More visits were accompanied by monitoring laboratory tests
      before the intervention (90.0%) compared with during the intervention (52.7%; p
      <0.001). A greater percentage of visits before the intervention included
      diagnostic imaging (15.4%) versus during the intervention (8.9%; p<0.001).
      CONCLUSIONS: We observed similar rates of adverse events before and during the
      implementation of TTT for RA. Rheumatology visits, use of laboratory monitoring,
      and diagnostic imaging did not increase during the TTT intervention. This article
      is protected by copyright. All rights reserved.

PMID- 30221840
TI  - Heat acclimatization blunts copeptin responses to hypertonicity from dehydrating
      exercise in humans.
AB  - Acclimatization favors greater extracellular tonicity from lower sweat sodium,
      yet hyperosmolality may impair thermoregulation during heat stress. Enhanced
      secretion or action of vasopressin could mitigate this through increased free
      water retention. Aims were to determine responses of the vasopressin surrogate
      copeptin to dehydrating exercise and investigate its relationships with tonicity
      during short and long-term acclimatization. Twenty-three participants completed a
      structured exercise programme following arrival from a temperate to a hot
      climate. A Heat Tolerance Test (HTT) was conducted on Day-2, 6, 9 and 23,
      consisting of 60-min block-stepping at 50% VO2 peak, with no fluid intake.
      Resting sweat [Na+ ] was measured by iontophoresis. Changes in body mass (sweat
      loss), core temperature, heart rate, osmolality (serum and urine) and copeptin
      and aldosterone (plasma) were measured with each Test. From Day 2 to Day 23,
      sweat [Na+ ] decreased significantly (adjusted P < 0.05) and core temperature and
      heart rate fell. Over the same interval, HTT-associated excursions were increased
      for serum osmolality (5 [-1, 9] vs. 9 [5, 12] mosm.kg-1 ), did not differ for
      copeptin (9.6 [6.0, 15.0] vs. 7.9 [4.3, 14.7] pmol.L-1 ) and were reduced for
      aldosterone (602 [415, 946] vs. 347 [263, 537] pmol.L-1 ). Urine osmolality was
      unchanging and related consistently to copeptin at end-exercise, whereas the
      association between copeptin and serum osmolality was right-shifted (P = 0.0109)
      with acclimatization. Unchanging urine:serum osmolality argued against increased
      renal action of vasopressin. In conclusion, where exercise in the heat is
      performed without fluid replacement, heat acclimatization does not appear to
      enhance AVP-mediated free water retention in humans.

PMID- 30221842
TI  - Dietary apple polyphenols increase skeletal muscle capillaries in Wistar rats.
AB  - Dietary apple polyphenols (AP) have been shown to exhibit beneficial effects on
      muscle endurance. Fast-to-slow change in the composition of myosin heavy chains
      was known as one of the molecular mechanisms. Here, we examined the effects of
      dietary AP on the capillaries and mitochondria in the rat skeletal muscle to
      elucidate the mechanisms underlying muscular endurance enhancement. Twenty-four
      Wistar male rats were divided into three groups, namely, the control group, 0.5%
      AP group, and 5% AP group (n = 8 in each group). After a feeding period of 4
      weeks, rats were dissected, gastrocnemius muscles were removed, and the density
      of capillaries and levels of mitochondrial proteins were analyzed. Capillary
      density of the gastrocnemius increased to 17.8% in rats fed with 5% AP as
      compared to the control rats. No significant change was observed in the
      mitochondrial content and dynamics (fusion/fission) of regulatory proteins. To
      investigate the mechanisms underlying the increase in the capillary density,
      positive (vascular endothelial cell growth factor, VEGF) and negative
      (thrombosponsin-1, TSP-1) factors of angiogenesis were analyzed. TSP-1 expression
      significantly decreased in rats fed with 0.5% AP and 5% AP by approximately 25%
      and 40%, respectively, as compared with the control rats. There were no
      significant differences in VEGF expression. Thus, dietary AP may increase the
      muscle capillary density by decreasing TSP-1 expression. We concluded that the
      increase in the capillary density and the fast-to-slow change in myosin heavy
      chains by AP feeding are the main causes for muscle endurance enhancement in
      Wistar rats.

PMID- 30221843
TI  - Effect of natural curcuminoids-intercalated layered double hydroxide nanohybrid
      against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis:
      A bactericidal, antibiofilm, and mechanistic study.
AB  - The study aimed to determine the antibacterial/antibiofilm effect and mechanism
      of interaction of curcuminoids-intercalated Mg/Al layered double hydroxide
      (curcuminoids-LDH) against three different bacteria. Antimicrobial effect of
      curcuminoids-LDH nanohybrid was investigated against P. aeruginosa, S. aureus,
      and E. faecalis (for both standard strains and clinical isolates), using agar
      well diffusion method. Minimum inhibitory concentrations (MIC) of planktonic
      bacteria were determined using the broth microdilution method. MIC of biofilms
      (MBIC50 ) and killing time for 48 hr matured biofilms were determined by MTT (3
      (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Scanning
      electron microscopy (SEM) was used to determine pre- and postexposure
      architecture of biofilms. The mechanism of the antibiofilm activity of
      curcuminoids-LDH was determined using UV-visible spectroscopy. All tested
      bacteria had given a zone of inhibition in the presence of curcuminoids-LDH. The
      MIC values were 0.200 g/ml for P. aeruginosa, 0.025 g/ml for S. aureus, and 0.100
      g/ml for E. faecalis. The 48 hr matured biofilms were reduced by curcuminoids-LDH
      with an MBIC50 of 0.100 g/ml. The minimum time to achieve MBIC50 was 3 hr, and
      the reduction was constant until 48 hr. SEM images showed a significant reduction
      of biofilm cell density and exopolymer matrics for all biofilms in the presence
      of curcuminoids-LDH. UV-visible studies revealed the antibiofilm activity of
      curcuminoids-LDH as due to the auto-oxidation of curcuminoids. The oxidation
      products are more limited in both product concentration per unit time and the
      variety of products, compared to pure curcuminoids, resulting in sharper UV
      visible peaks than in the case of the latter. Curcuminoids-LDH has a potential
      antibacterial activity against P. aeruginosa, S. aureus, and E. faecalis. An
      antibiofilm activity has been achieved within 3 hr of the treatment. Curcuminoids
      released from the LDH showed the antibacterial activity due to oxidation products
      interfering with bacterial cell functions, and also encapsulation in the LDH
      causes curcuminoids to exhibit the activity in a persistent manner compared to
      pure curcuminoids.

PMID- 30221844
TI  - Do structures matter any more?
AB  - This Editorial discusses some recent corrections to published structural data in
      which all conclusions were claimed to be valid even if the presented structures
      were wrong.

PMID- 30221847
TI  - Corrigendum: Shape-Controllable and Fluorescent Supramolecular Organic Frameworks
      Through Aqueous Host-Guest Complexation.

PMID- 30221849
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 34/2018.

PMID- 30221846
TI  - An Aurora kinase inhibitor, AMG900, inhibits glioblastoma cell proliferation by
      disrupting mitotic progression.
AB  - The Aurora kinase family of serine/threonine protein kinases comprises Aurora A,
      B, and C and plays an important role in mitotic progression. Several inhibitors
      of Aurora kinase have been developed as anti-cancer therapeutics. Here, we
      examined the effects of a pan-Aurora kinase inhibitor, AMG900, against
      glioblastoma cells. AMG900 inhibited proliferation of A172, U-87MG, and U-118MG
      glioblastoma cells by upregulating p53 and p21 and subsequently inducing cell
      cycle arrest and senescence. Abnormal cell cycle progression was triggered by
      dysregulated mitosis. Mitosis was prolonged due to a defect in mitotic spindle
      assembly. Despite the presence of an unattached kinetochore, BubR1, a component
      of the spindle assembly checkpoint, was not recruited. In addition, Aurora B was
      not recruited to central spindle at anaphase. Abnormal mitotic progression
      resulted in accumulation of multinuclei and micronuclei, a type of chromosome
      missegregation, and ultimately inhibited cell survival. Therefore, the data
      suggest that AMG900-mediated inhibition of Aurora kinase is a potential anti
      cancer therapy for glioblastoma.

PMID- 30221848
TI  - Corrigendum: Spontaneously Self-Assembled Naphthalimide Nanosheets: Aggregation
      Induced Emission and Unveiling a-PET for Sensitive Detection of Organic Volatile
      Contaminants in Water.

PMID- 30221850
TI  - Clinical Images: Arthritis mutilans in systemic sclerosis.

PMID- 30221851
TI  - A prospective, randomized, single-blinded trial for improving health outcomes in
      rhinology by the use of personalized video recordings.
AB  - BACKGROUND: Clear patient-physician communication is critical in improving
      patient compliance, outcomes, and satisfaction. However, constraints of shortened
      clinic visits, patient anxiety, and poor recall can cause significant barriers to
      effective communication. We hypothesized that the ability to view patient
      physician counseling videos at home would improve health outcomes. METHODS:
      Patients in a tertiary rhinology clinic were enrolled into a single-blinded
      prospective study after obtaining institutional review board (IRB) approval and
      informed consent. All enrollees had a short summary of their clinical encounter
      video-recorded with a tablet using Medical Memory, a Health Insurance Portability
      and Accountability Act (HIPAA)-compliant software system. Patients were
      randomized to receive access to their videos by our research coordinator, and
      outcomes included questionnaires at the first postoperative visit to assess
      patient recall and satisfaction. RESULTS: A total of 101 patients were enrolled.
      Half of those with video access watched the video at least once, on average 3.44
      times. Of those without access, 90% would have liked the option. Those with video
      access had a higher percentage of correct answers to questions regarding surgical
      risk and extent of surgery; however, there was no significant difference between
      the 2 groups. CONCLUSION: Our results show that patients in both groups were
      enthusiastic about this technology and often shared their videos with family and
      friends. Video-recordings of physician-patient encounters may be a possible
      solution to improve physician-patient communication.

PMID- 30221852
TI  - [REHABILITATION MEDICINE ADDS LIFE TO THE YEARS].
AB  - INTRODUCTION: The Reuth Rehabilitation Hospital is a university-affiliated
      Medical Center, the biggest of its kind in Israel. Reuth's unique structure
      combines both a Rehabilitation Hospital with a Geriatric Medical Center. The
      hospital offers both inpatient and outpatient services with a diversity of
      conditions through a rehabilitative, holistic, multi- and interdisciplinary
      approach. Patients and their families are at the center of attention, alongside
      focus on professional excellence, academic instruction and research and
      development. In the current paper, the principles and unique approach guiding the
      activities and development of the Reuth Rehabilitation Hospital are presented.

PMID- 30221853
TI  - [EXECUTIVE FUNCTIONS AND DAILY FUNCTIONS, ROAD SIGN RECOGNITION AND DRIVING SELF
      REPORT AMONG HEALTHY AND POST-STROKE DRIVERS].
AB  - INTRODUCTION: Driving is an essential part of occupational performance. In
      determining potential driving competence, there is a lack of screening tools to
      ascertain who should be referred for further assessment in Occupational Therapy
      or at the Medical Institute for Road Safety. AIMS: To assess the relationship
      between executive-function, daily-functions and driving behavior measures in
      unimpaired and neurologically impaired populations. BACKGROUND: Although the
      research findings were not statistically significant, the trend points to the
      correlation between executive-function measures and self-report driving ability.
      Road sign recognition tests and daily-functions were found to be potential
      screening tools for assessing driving potential, but a larger sample size is
      recommended to confirm results. METHODS: An exploratory study that included 19
      subjects - 10 without neurological impairments - and 9 post-stroke. Self-report
      questionnaires on driving ability, executive-functions and daily-function were
      administered. Post-stroke subjects were also assessed on road sign recognition.
      RESULTS: The research hypothesis was not confirmed. Three moderately correlated
      but statistically insignificant correlations were found: in unimpaired subjects
      between the driving self-report and functional status; in post-stroke subjects -
      between the driving self-report and self-monitoring and behavioral-regulation
      skills and in the road sign recognition tests - between executive and daily
      function measures. CONCLUSIONS: If the trends were strengthened in a larger
      sample size the use of driving behavior self-report questionnaires, executive
      function, daily-function and road sign recognition tests as screening tools for
      the unimpaired and post-stroke populations would be effective/recommended.
      DISCUSSION: Present findings of correlations between self-report of driving
      skills and behavioral regulation skills confirm previous research findings.

PMID- 30221854
TI  - [RECRUITMENT PATTERNS OF HOMOLOGOUS MUSCLES DURING UNILATERAL MOVEMENT IN
      HEMIPARETIC SUBJECTS].
AB  - INTRODUCTION: The presence of unintentional muscular activity, with or without
      overt movement, in the homologue muscle contralateral to the limb being activated
      voluntarily, has been documented in both healthy and hemi-paretic populations.
      This activity has been termed contra-lateral motor irradiation (CMI), mirror
      movement, associated movement, motor overflow or synkinesis. AIMS: To
      characterize the CMI phenomenon amongst healthy controls and patients with
      varying degrees of motor ability and also to assess the ability to consciously
      control this phenomenon. METHODS: A cross-sectional design was used to study sub
      acute (within 6 weeks of the insult) stroke patients; assessments were performed
      within two weeks of commencing rehabilitation and again after 4 weeks. Healthy
      controls were assessed once. A simple motor task, unilateral extension of wrist
      and fingers, was examined. Concomitant muscular activity of the homologue muscle
      on the contralateral upper limb was the focus of interest; EMG activation was
      monitored on both sides. The Fugl-Meyer test was used to assess the residual
      motor capacity of the upper limb. RESULTS: CMI was demonstrated only in the non
      paretic hand during voluntary activation of the paretic hand. The study group,
      unlike the control group, was unable to consciously reduce CMI. CONCLUSIONS:
      Although the mechanisms underlying CMI are poorly understood, they reflect an
      important aspect of inter-hemispheric relationship in motor control. In stroke
      patients, CMI monitoring by surface EMG can be used to assess its characteristics
      following damage to different elements of the motor system.

PMID- 30221855
TI  - [FALL PREDICTION AND FALL SEVERITY IN REHABILITATION HOSPITAL].
AB  - AIMS: We tested whether the Farmer questionnaire is valid for fall risk
      assessment in Hebrew. We tested whether NDNQI (National Database of Nursing
      Quality Indicators) is valid for fall severity evaluation in Hebrew. Finally, we
      tested whether the Farmer and NDNQI are correlated. BACKGROUND: Patients in
      rehabilitation hospitals are exposed to fall-risking conditions. Falls with
      severe outcomes can extend the hospitalization, and increase the workload on
      health systems. Fall risk assessment at the beginning of hospitalization is
      crucial for making supportive and preventive adjustments. The Israel Ministry of
      Health obliges using fall risk assessment at hospitalization. Nonetheless, fall
      risk assessment has not been validated in Hebrew, and has not been tested for
      prediction power of fall severity outcome. METHODS: Farmer measurement was
      validated in 1187 patients retrospectively, out of whom 288 had fallen during
      hospitalization. Twenty-five fall cases with varying severities were ranked by 47
      staff members for their fall severity score. Non-parametric Spearman's
      correlation was tested between Farmer and NDNQI measurements. RESULTS: Mean
      Farmer value of the falling group was larger than the mean Farmer value of the
      non-falling group (F=9.5, pv=0.002). Variability between raters was smaller than
      variability between conditions in NDNQI (ICC(2,1)=0.75). Farmer index was not
      correlated with NDNQI score (rho=0.092, pv=0.118). CONCLUSIONS: Farmer
      measurement is a valid tool for fall risk assessment in Hebrew. NDNQI is a valid
      tool for evaluation of fall severity. Farmer index is not predictive of fall
      severity. DISCUSSION: There is a need for predictive measures of fall severity
      outcomes. We recommend using fall severity scores for ranking the intervention's
      success.

PMID- 30221857
TI  - [AN INVESTIGATION INTO THE ROLE OF A REHABILITATION HOSPITAL PHARMACIST IN
      DETERMINING DISCREPANCIES AND MEDICATION ERRORS DURING PATIENTS' ADMISSION].
AB  - INTRODUCTION: The importance of correcting medication errors at hospital
      admission is paramount for promoting error-free delivery and continuity of care.
      Recently stakeholders have paid considerable attention to patient safety in acute
      care hospitals but less is known about discrepancies and medication errors during
      patients' admission in other health care settings, such as post-acute care
      providers. An increased understanding of errors that occur in rehabilitation
      hospitals, would better equip stakeholders in taking actions to improve the
      safety of patient care in this unique setting. AIMS: The primary aim of the
      current study, conducted in a rehabilitation health care setting, is to study the
      pharmacist's role in identifying and preventing unintended medication
      discrepancies at the time of their hospital admission. The lack of available
      information on medications errors associated with medicines' risk factors and
      patients' characteristics, led the researcher to her secondary objective: to
      study the source of error, type of discrepancy and class of medicine most
      frequently implicated during the transition of care from an acute to a
      rehabilitation hospital. METHODS: The researcher performed a retrospective
      investigation and study of 356 patients with 3071 prescription medications
      referred from an acute hospital. The inclusion criteria also included ventilated
      patients over the age of 18 who received more than five prescription-only
      medicines. Over a period of 12 months, the investigator ascertained what
      medications were used prior and post-admission stage and then compared these
      drugs. The discrepancies identified were discussed with the attending physician.
      Unintended discrepancies were classified as errors. RESULTS: Unexplained errors
      which resulted in physician changes affected 154 patients, 43% of the total
      number of the study participants. The findings show that the most common cause of
      error found during the reconciliation of medicines at the point of admission is
      the use of patients own medications in the process. The most accurate and up to
      date source of information during the reconciliation process is the medication
      list brought with the patient upon admission. The wrong route of administration
      was the most common type of error that was found. Errors were concerned with
      important drug categories such as cardiovascular and antidiabetic drugs. The
      average number of drugs per patient is 9, while each of the studied population
      had a mean of two or more errors in admission. Although men were treated with an
      average of 10 medicines and females received only 8, the number of discrepancies
      was higher in females. CONCLUSIONS: Pharmacists play an important role in
      determining discrepancies and medication errors during patients' admission. This
      study provides an insight into the discrepancies that occur in this unique
      setting. Stakeholders may wish to adopt the recommendations provided by the
      author and act in order to improve the patients' safety in rehabilitation
      hospitals. Some of the recommendations are also applicable to other health care
      settings.

PMID- 30221856
TI  - [FROM THEORY TO THE CLINIC - IS IT POSSIBLE TO DETECT DIFFERENT TYPES OF ANOMIA
      ACCORDING TO THE LEXICAL RETRIEVAL MODEL?]
AB  - INTRODUCTION: The lexical retrieval model describes the process of naming - from
      the level of an abstract concept representation to the production of the word.
      Lexical retrieval includes several distinct levels. A deficit in any of these
      levels causes anomia, a naming deficit, and deficits in different levels cause
      different types of anomia. AIMS: To examine whether the theoretical model can be
      applied in the clinic. Namely, whether it is possible to identify, for a specific
      patient, the exact impaired lexical retrieval level, and to show that different
      patients are impaired in different levels. METHODS: The performance of 24
      participants with aphasia, with lexical retrieval deficits, were analyzed. The
      analysis included performance on a naming test - including analysis of error
      types and of the effects that modulate naming errors. We also analyzed the
      performance in other language tasks that examine the different levels of lexical
      retrieval, including tasks that do not involve naming. RESULTS: Different types
      of anomia were found for the different participants. The various types of anomia
      are reflected in different sorts of naming errors, in different effects that
      modulate naming errors, and in different performance patterns in the other
      language tasks. CONCLUSIONS: The theoretical model of lexical retrieval can
      underpin descriptions of clinical phenomena. The findings support the view that
      the relations between theory and clinic are bidirectional - theories constitute
      an anchor for the description of clinical phenomena, and clinical findings can
      support, or refute, theory. DISCUSSION: The distinction between the different
      types of anomia is important for choosing the appropriate treatment for each
      patient.

PMID- 30221858
TI  - [PARAPARESIS DUE TO RHABDOMYOLYSIS AND A COMPARTMENT SYNDROME IN FIVE PATIENTS
      WHO HAD BEEN IN A PROLONGED SLEEP IN A SITTING POSITION].
AB  - INTRODUCTION: Five patients developed symmetrical paraparesis due to a
      combination of: compartment syndrome, rhabdomyolysis, renal failure, and
      demyelinative sensory-motor polyneuropathy, after prolonged sleep in a sitting
      position. The long deep sleep was induced by consumption of alcohol or drugs.
      Long-term follow-up showed that these patients remained paraparetic. No damage to
      the autonomic nervous system was found. Although some suspected that these
      patients developed "intensive care neuropathy", we suggest that this syndrome is
      different, and should be regarded as a "new syndrome".

PMID- 30221859
TI  - [CHANGES IN THE WAY WE OBSERVE, ASSESS AND TREAT APHASIA: FROM THE TRADITIONAL
      APPROACH TO THE PSYCHOLINGUISTIC AND SOCIAL APPROACHES].
AB  - INTRODUCTION: Aphasia is an acquired language impairment, initially identified
      and described before the 19th century. According to traditional models (Wernicke
      Lichtheim-Geschwind) the aphasic symptoms can be clustered into particular
      syndromes, such as Broca's, Wernicke's, Conduction aphasias, and more. Each
      syndrome is allegedly associated with a specific anatomical site. The major
      motivation for this model was to use the behavioral symptoms to learn about
      language and brain relationships. However, current advanced imaging techniques
      identify more precisely the loci of the deficit. Moreover, the model frequently
      fails to adequately describe the clinical symptoms, a description that is crucial
      for understanding the language deficit and for choosing the relevant treatment.
      For more than three decades, two alternative models are being used in the
      clinical setting and in research. First, the psycholinguistic model, which
      describes the normal stages that are involved in language processing. On the
      basis of this model it is possible to detect, for each individual with aphasia,
      the specific impaired stage or stages underlying the language deficits. Second,
      the social model of aphasia based on the ICF definitions of the World Health
      Organization. According to this model, it is suggested that the speech therapy
      intervention should focus not only on the language deficits but also on
      communication per se in order to enable the individual with aphasia to
      communicate with others despite the language deficits. In the current paper we
      will review these two models and their clinical implications.

PMID- 30221860
TI  - [PHYSICIANS RIGHTEOUS AMONG THE NATIONS AND OTHER HEROES].
AB  - INTRODUCTION: As of 1.1.2013, out of 24,811 persons awarded the status of
      Righteous Among the Nations, 245 (1%) were physicians and 31 were medical
      students. They were active in helping and saving Jews in various ways: surgery
      for hiding signs of Jewish identity, hospitalizations, smuggling medical supplies
      into the ghettos, providing false documents, hiding people and active fighting.
      We must remember them and pay them homage. We are equally obligated to the Jewish
      physicians, who saved the lives of other Jews during the Holocaust, at the risk
      of their own lives.

PMID- 30221861
TI  - [HOW MANY PHYSICIANS ARE ACTIVELY PRACTICING MEDICINE IN ISRAEL? ON THE
      DIFFERENCES BETWEEN VARIOUS METHODS OF MEASUREMENT].
AB  - INTRODUCTION: In 2018, Israel replaced the workforce surveys of the Central
      Bureau of Statistics with administrative data files, as the source of its reports
      to the OECD on the number of physicians practicing medicine and their percentage
      of the population. In the wake of the change, the scope of the medical workforce
      reported by Israel dropped by approximately 9%-15% in each one of the years from
      2012-2015. Furthermore, while according to the previous measurement approach,
      Israeli figures were consistently equal to or higher than the yearly OECD
      averages, according to the new method these figures are lower than the averages
      of other OECD members. Essentially, according to the new data, the number of
      physicians practicing medicine in Israel straddles the minimum desirable amount
      recommended in the past by workforce planning committees in Israel. The new data
      are largely accordant with the feeling of distress and shortage in the medical
      workforce, which pervades the health system for many years, and simultaneously
      raise questions as to the reliability of official Israeli data as reported to the
      OECD - data upon which researchers, policy makers, the media and the public rely.
      Consequently, it is recommended to consistently improve the measurement and
      reporting to international organizations and to increase transparency regarding
      the measurement methods of various indicators in the health field.

PMID- 30221862
TI  - [ENDOMETRIAL-PATTERN IN EARLY PREGNANCY AND CORRELATION WITH ECTOPIC-PREGNANCY].
AB  - INTRODUCTION: Ectopic-pregnancy is a leading cause of pregnancy-related maternal
      death in the first trimester. Early sonographic diagnostic ability of ectopic
      pregnancy is limited. There is an increasing need to identify sonographic markers
      that can assist with the diagnosis. OBJECTIVES: To characterize the endometrial
      pattern by transvaginal-ultrasound as an early marker for ectopic-pregnancy,
      before demonstration of tubal mass. METHODS: A multicenter prospective study that
      included 52 women with a positive HCG test, referred to the ultrasound-unit with
      a diagnosis of pregnancy of unknown location. A transvaginal ultrasound was
      performed focusing on the endometrial-pattern, and classifying findings into four
      categories: homogeneous, heterogeneous, three-laminar and existence of fluid
      collection within the endometrial cavity. RESULTS: A total of 38 women were
      diagnosed with ectopic-pregnancy. Three women demonstrated normal intrauterine
      pregnancy, 3 others had an early miscarriage and 8 women were excluded from the
      study. No statistically significant differences were found between the groups in
      terms of demographic, clinical, or laboratory characteristics. Three-laminar
      pattern had 94% positive predictive value and 18% negative predictive value for
      ectopic-pregnancy, with sensitivity and specificity of 42% and 83%, respectively.
      Changes in the endometrial-pattern were demonstrated during subsequent tests when
      performed. CONCLUSIONS: The use of transvaginal-ultrasound to identify the
      endometrial-pattern in early pregnancy does not require significant expertise.
      The identification of three-laminar endometrium in pregnancies of an unknown
      location, should raise the suspicion of ectopic-pregnancy. DISCUSSION: Three
      laminar pattern has high PPV for predicting ectopic pregnancy in women with
      pregnancy of an unknown location. The changes in the endometrial-pattern during
      subsequent tests, especially the transition of three-laminar into homogeneous
      pattern, a phenomenon not reported in previous studies, raised the need for
      further studies.

PMID- 30221863
TI  - [PRINCIPLES FOR THE INTERPRETATION OF CARDIOPULMONARY EXERCISE TESTS (CPET)].
AB  - INTRODUCTION: The cardiopulmonary exercise test (CPET) permits the most accurate
      and reproducible quantification of cardiopulmonary fitness, a grading of the
      etiology and severity of cardiopulmonary impairments, and an objective assessment
      of the response to an intervention. Moreover, over the last three decades, a
      large volume of research has been directed toward the utility of CPET as a
      diagnostic and prognostic tool; these studies have established CPET as a
      scientifically sound and, therefore, clinically valuable method for accurately
      assessing exercise limitation and prognosis in various disease states. The CPET
      is relatively easy to perform, yet complex in the interpretation of the results.
      The current review presents the principles of the analytic process of the test
      results, in order to obtain possible diagnoses.

PMID- 30221864
TI  - Magnesium Deficiency and Minimal Hepatic Encephalopathy among Patients with
      Compensated Liver Cirrhosis.
AB  - BACKGROUND: Magnesium is an essential intracellular cation. Magnesium deficiency
      is common in the general population and its prevalence among patients with
      cirrhosis is even higher. Correlation between serum levels and total body content
      is poor because most magnesium is intracellular. Minimal hepatic encephalopathy
      is a subclinical phase of hepatic encephalopathy with no overt symptoms.
      Cognitive exams can reveal minor changes in coordination, attention, and
      visuomotor function, whereas language and verbal intelligence are usually
      relatively spared. OBJECTIVES: To assess the correlation between intracellular
      and serum magnesium levels and minimal hepatic encephalopathy. METHODS:
      Outpatients with a diagnosis of compensated liver cirrhosis were enrolled in this
      randomized, double-blinded study. Patients were recruited for the study from
      November 2013 to January 2014, and were randomly assigned to a control (placebo)
      or an interventional (treated with magnesium oxide) group. Serum and
      intracellular magnesium levels were measured at enrollment and at the end of the
      study. Cognitive function was assessed by a specialized occupational therapist.
      RESULTS: Forty-two patients met the inclusion criteria, 29 of whom were included
      in this study. Among these, 83% had abnormal cognitive exam results compatible
      with minimal hepatic encephalopathy. While only 10% had hypomagnesemia, 33.3% had
      low levels of intracellular magnesium. Initial intracellular and serum magnesium
      levels positively correlated with cognitive performance. CONCLUSIONS: Magnesium
      deficiency is common among patients with compensated liver cirrhosis. We found an
      association between magnesium deficiency and impairment in several cognitive
      function tests. This finding suggests involvement of magnesium in the
      pathophysiology of minimal hepatic encephalopathy.

PMID- 30221865
TI  - Post-cardiac Implantable Electronic Devices: Inflammation of the Pocket. Should
      We Be More Aggressive?
AB  - BACKGROUND: Pacemaker pocket early post-implantation inflammation (EPII) is
      defined as clinical signs of local erythema without any systemic signs of
      infection occurring early after implantation. Data on the best treatment regimen
      for apparent superficial EPII is scarce. OBJECTIVES: To investigate the
      prognostic value of medical treatment, rather than extraction surgery, in
      patients with EPII. METHODS: Data from 6013 consecutive patients who underwent
      cardiac implantable electronic device (CIED) implantation or replacement from
      2007-2015 were retrospectively analyzed; 40 (0.7%) presented with EPII. Our goal
      was the absence of major complications and to avoidance of extraction. RESULTS:
      Patients with EPII were initially treated medically. Nineteen (47%) (group A)
      recovered with antibiotic treatment only. In the other 21 patients (53%) (group
      B), CIED extraction was performed. Group B had more major complications compared
      to group A (15 [71%] vs. 0 [0%], P < 0.001). The only significant difference in
      baseline characteristics was history of non-initial procedure. While 86% of group
      B patients had a previous non-initial procedure, only 53% of group A patients
      underwent previous replacement (P < 0.05). In multivariate analysis, previous non
      initial procedure was the only predictor for need of extraction at 1 year, hazard
      ratio 3.5, 95% confidence interval 1.001-11.73, P < 0.05. CONCLUSIONS:
      Conservative treatment in patients with EPII after non-initial procedure can lead
      to serious adverse events resulting in the need for extraction. Close follow-up
      and aggressive treatment should be considered early in the therapeutic course.

PMID- 30221866
TI  - Prevalence and Significance of Restrictive Filling Pattern in an Echocardiography
      Laboratory.
AB  - BACKGROUND: A cardiac restrictive filling patterns are associated with
      unfavorable prognoses. Cardiac interventions may change the natural history of
      patients. OBJECTIVES: To investigate the prevalence of restrictive filling
      pattern in routine echocardiographic examinations and their association with
      morbidity and mortality. METHODS: The clinical and echocardiographic data of
      patients with newly diagnosed restrictive filling pattern were analyzed and
      summarized. RESULTS: Among 8000 patients who underwent an echocardiographic
      examination in our hospital in 2013, a restrictive filling pattern was identified
      in 256. Of these, 134 showed a restrictive filling pattern that was newly
      diagnosed. Mean age was 69 years. Hypertension, diabetes, and ischemic heart
      disease were found in 81%, 60%, and 53%, respectively. Left ventricular ejection
      fraction was 42% +/- 16%. Severe valvular abnormalities were found in 18%. During
      follow-up (29 +/- 15 months), 40% of patients died. The strongest predictor of
      mortality (73%) was moderate or more advanced aortic stenosis, P = 0.005. Renal
      failure was an important independent predictor of mortality (53%, P < 0.05). A
      very high E/E' ratio >= 20, was another independent mortality predictor (50%, P <
      0.03). Patients who died were less likely to have undergone cardiac interventions
      than those who survived (26% vs. 45%, P < 0.03). CONCLUSIONS: Prevalence of
      restrictive filling among echocardiographic studies is 3.2%. In a half of these,
      the restrictive filling pattern is a new diagnosis. Patients who are diagnosed
      with a new restrictive filling pattern have higher mortality rates. Patients with
      restrictive filling should be evaluated thoroughly for possible coronary artery
      or valvular heart disease.

PMID- 30221867
TI  - RPM Inspiration Gating: Improving Radiotherapy for Left Breast Cancer Patients
      with Anterior Heart Position.
AB  - BACKGROUND: Adjuvant radiotherapy for breast cancer reduces local recurrence and
      improves survival. In patients with left sided breast cancer, anterior heart
      position or medial tumor location may cause inadequate breast coverage due to
      heart shielding. Respiration gating using the Real-time Position Management (RPM)
      system enables pushing the heart away from the tangential fields during
      inspiration, thus optimizing the treatment plan. OBJECTIVES: To compare breathing
      inspiration gating (IG) techniques with free breathing (FB), focusing on breast
      coverage. METHODS: The study comprised 49 consecutive patients with left sided
      breast cancer who underwent lumpectomy and adjuvant radiation. RPM was chosen due
      to insufficient breast coverage caused by an anterior heart position or medial
      lumpectomy cavity. FB and IG computed tomography simulations were generated for
      each patient. Breast (PTVbreast) and lumpectomy cavity (CTVlump) were defined as
      the target areas. Optimized treatment plans were created for each scan. A
      dosimetric comparison was made for breast coverage and heart and lungs doses.
      RESULTS: PTVbreast V95% and mean dose (Dmean) were higher with IG vs. FB (82.36%
      vs. 78.88%, P = 0.002; 95.73% vs. 93.63%, P < 0.001, respectively). CTVlump V95%
      and Dmean were higher with IG (98.87% vs. 88.92%, P = 0.001; 99.14% vs. 96.73%, P
      = 0.003, respectively). The cardiac dose was lower with IG. The IG left lung
      Dmean was higher. No statistical difference was found for left lung V20.
      CONCLUSIONS: In patients with suboptimal treatment plans due to anterior heart
      position or medial lumpectomy cavity, RPM IG enabled better breast/tumor bed
      coverage and reduced cardiac doses.

PMID- 30221868
TI  - Mortality and Function after Hip Fractures in Different Ethnic Populations in
      Israel.
AB  - BACKGROUND: Mortality and decrease in function after hip fracture are
      significantly related to patient factors including age, gender, co-morbidities,
      and mental status. Several studies demonstrated ethnic disparities in incidence,
      mortality, and functional outcome after hip fractures in the United States.
      OBJECTIVES: To assess the relationship between ethnicity and hip fracture
      incidence and outcomes of mortality, functional change, and perioperative
      complications in the Israeli population. METHODS: We reviewed our institutional
      hip fracture registry for all patients from 2014-2015. Patients with incomplete
      data, < 60 years of age, or pathologic and periprosthetic fractures were
      excluded. Our study comprised 693 patients. Ethnicity was based on country of
      birth. Specifically, for those born in Israel, the nationality of either Jewish
      or Arab was further dichotomized. Perioperative complications, mortality, and
      mobility status at 1 year follow-up were recorded. The ethnicities of 27,130
      patients admitted to the medicine and surgical wards during the same time
      interval served as a control group for the hip fracture cohort. RESULTS:
      Immigrants from Europe and America had the highest incidence of hip fractures.
      Fracture types varied in incidence in groups with 70% of extracapsular hip
      fractures occurring in Arabs and immigrants from Eastern countries, compared to
      60% in immigrants from Western countries and the former Soviet Union. Mortality,
      perioperative complications, and mobility at 1 year were similar in all ethnic
      groups. CONCLUSIONS: Our study demonstrated significant differences in incidence
      and fracture characteristic among ethnicities, but no difference in patient
      outcome. These findings differed from the available North American studies.

PMID- 30221869
TI  - Familial Occurrence of Idiopathic Intracranial Hypertension.
AB  - BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disorder of unknown
      etiology. Its occurrence in the general population is 1/100,000, and 20/100,000
      among overweight women of childbearing age. Familial occurrence is reportedly
      uncommon and not well-characterized. OBJECTIVES: To describe a familial
      association with IIH. METHODS: We conducted a retrospective chart review of all
      familial cases of IIH examined in the neuro-ophthalmology clinic of our medical
      center between January 2006 and June 2013. RESULTS: Of a total of 520 patients
      with IIH, 15 had other family members with IIH (from seven different families).
      The family relation was a mother and daughter in two families, a brother and
      sister in four families, and an aunt and two first-degree cousins in the seventh
      family. Symptoms, course of disease, and risk factors were similar among the
      relatives of all seven families, except for the age at diagnosis, which was
      different in one family. All of the adult patients of six families were obese
      (body mass index 25-35 kg/m2), and all of the members of the other family were
      morbidly obese. There was no association between other systemic risk factors and
      IIH. CONCLUSIONS: IIH occurrence within a family is more common than previously
      believed, and its incidence in families is more common than in the general
      population. The clinical course appears to be similar in family members. Our
      findings suggest a genetic predisposition. Further investigation of familial
      cases may yield useful information on the pathogenesis and genetic nature of this
      condition.

PMID- 30221870
TI  - Psychopathology of Israeli Soldiers Presenting to a General Hospital Emergency
      Department: Lessons for the Attending Physician and Psychiatrist.
AB  - BACKGROUND: There is scant research on the psychopathology of Israeli soldiers
      who present to a general hospital emergency department (ED). OBJECTIVES: To
      assess the psychopathology among a cohort of Israeli soldiers who presented to a
      general hospital ED for mental health assessment. METHODS: The demographic and
      clinical characteristics of 124 consecutive soldiers who presented to the ED for
      psychiatric assessment between January 2008 and September 2012 were reviewed.
      Twenty-seven soldiers from the cohort were contacted for follow-up by telephone
      on average 52 months later. RESULTS: The reasons for presentation to the ED,
      usually during the early stages of military service, included self-harming
      behavior, suicidal ideation, somatoform complaints, and dissatisfaction with
      their military service. Psychiatric diagnoses included adjustment disorder and
      personality disorder. Self-harming behavior/suicidal ideation was significantly
      correlated with unspecified adjustment disorder (P = 0.02) and personality
      disorder (P = 0.001). At follow-up, there was a lack of substantial
      psychopathology: none of the subjects engaged in self-harming behavior/suicidal
      ideation and a consistent trend was observed toward clinical improvement.
      CONCLUSIONS: Psychiatric intervention of soldiers who present to a general
      hospital ED because of emotional difficulties may provide the opportunity for
      crisis intervention and validation of the soldier's distress. To the best of our
      knowledge this is the first Israeli study of psychopathology among soldiers who
      presented to an ED.

PMID- 30221871
TI  - Trends and Outcomes in Heart Transplantation over the Past Three Decades: A
      Single Tertiary Center Experience in Israel.
AB  - BACKGROUND: Heart transplantation (HT) is the treatment of choice for patients
      with end-stage heart failure. The HT unit at the Sheba Medical Center is the
      largest of its kind in Israel. OBJECTIVES: To evaluate the experience of HT at a
      single center, assess trends over 3 decades, and correlate with worldwide data.
      METHODS: Between 1990 and 2017, we reviewed all 285  adult HT patients. Patients
      were grouped by year of HT: 1990-1999 (decade 1), 2000-2009 (decade 2), and 2010
      2017 (decade 3). RESULTS: The percentage of women undergoing HT has increased and
      etiology has shifted from ischemic to non-ischemic cardiomyopathy (10% vs. 25%, P
      = 0.033; 70% vs. 40% ischemic, for decades 1 vs. 3, respectively). Implantation
      of left ventricular assist device as a bridge to HT has increased. Metabolic
      profile has improved over the years with lower low-density lipoprotein, diabetes,
      and hypertension after HT (101 mg/dl, 27%, and 41% at decade 3, respectively).
      There has been a prominent change in immunosuppressive treatments, currently more
      than 90% are treated with tacrolimus, compared with 2.7% and 30.9% in decades 1
      and 2, respectively (P < 0.001). Cardiac allograft vasculopathy (CAV) rates have
      declined significantly (47% vs. 17.5% for decades 1 and 2, P < 0.001) as have the
      combined endpoint of CAV/death. Similarly, the current incidence of acute
      rejections is significantly lower. CONCLUSIONS: Our analysis of over 25 years of
      a single-center experience with HT shows encouraging improved results, which are
      in line with worldwide standards and experience.

PMID- 30221872
TI  - Characteristics and Outcomes of Ptyalism Gravidarum.
AB  - BACKGROUND: Ptyalism gravidarum (PG) is a condition of hypersalivation that
      affects pregnant women early in gestation. Symptoms include massive saliva
      volumes (up to 2 liters per day), swollen salivary glands, sleep deprivation,
      significant emotional distress, and social difficulties. OBJECTIVES: To examine
      maternal and fetal characteristics and pregnancy outcomes of patients with PG.
      METHODS: Patients diagnosed with PG in our clinic during the years 2001-2016 were
      identified and contacted. Demographic data were extracted from patient charts and
      clinical and outcome data was collected via telephone interviews. RESULTS: The
      incidence of PG was 1/963 (0.09%) in our sample. Eleven out of 22 women (40%)
      with PG were also diagnosed with hyperemesis gravidarum. Fetal gender did not
      increase the risk. Of the mothers presenting with PG, 37% had a positive family
      history for this condition. There was no associated increase in the rate of fetal
      or maternal complications. Two women reported a resolution of the symptoms
      immediately following hypnosis with acupuncture treatment. CONCLUSIONS: Although
      PG represents an unpleasant mental and physical condition, it does not pose any
      specific risk to the health of the mother or increase adverse perinatal outcomes
      for the fetus. Alternative medicine could play a role in the treatment of PG.

PMID- 30221873
TI  - Autism Spectrum Disorder: Evolution of Disorder Definition, Risk Factors and
      Demographic Characteristics in Israel.

PMID- 30221874
TI  - Radiotherapy for Breast Cancer: Curing the Cancer While Protecting the Heart.

PMID- 30221876
TI  - Central Diabetes Insipidus as an Early Presentation of Erdheim-Chester Disease.

PMID- 30221875
TI  - Autism Spectrum Disorder in Israel.

PMID- 30221877
TI  - Petersen Hernia in Pregnancy: A Report of Two Cases and Their Radiologic
      Findings.

PMID- 30221878
TI  - Surgical Treatment of Hepatocellular Carcinoma with a Tumor Thrombus Extending
      into the Right Atrium.

PMID- 30221880
TI  - Treading on an Eggshell.

PMID- 30221879
TI  - Mucor Appendicitis Resolution Following Surgical Excision without Antifungal
      Therapy.

PMID- 30221881
TI  - A Review on the Receptor-ligand Molecular Interactions in the Nicotinic Receptor
      Signaling Systems.
AB  - Nicotine is regarded as the main active addictive ingredient in tobacco products
      driving continued tobacco abuse behavior (smoking) to the addiction behavior,
      whereas nicotinic acetylcholine receptors (nAChR) is the crucial effective
      apparatus or molecular effector of nicotine and acetylcholine and other similar
      ligands. Many nAChR subunits have been revealed to bind to either
      neurotransmitters or exogenous ligands, such as nicotine and acetylcholine, being
      involved in the nicotinic receptor signal transduction. Therefore, the nicotinic
      receptor signalling molecules and the receptor-ligand molecular interactions
      between nAChRs and their ligands are universally regarded as crucial mediators of
      cellular functions and drug targets in medical treatment and clinical diagnosis.
      Given numerous endeavours have been made in defining the roles of nAChRs in
      response to nicotine and other addictive drugs, this review focuses on studies
      and reports in recent years on the receptor-ligand interactions between nAChR
      receptors and ligands, including lipid-nAChR and protein-nAChR molecular
      interactions, relevant signal transduction pathways and their molecular
      mechanisms in the nicotinic receptor signalling systems. All the references were
      carefully retrieved from the PubMed database by searching key words "nicotine",
      "acetylcholine", "nicotinic acetylcholine receptor(s)", "nAChR*", "protein and
      nAChR", "lipid and nAChR", "smok*" and "tobacco". All the relevant referred
      papers and reports retrieved were fully reviewed for manual inspection. This
      effort intend to get a quick insight and understanding of the nicotinic receptor
      signalling and their molecular interactions mechanisms. Understanding the
      cellular receptor-ligand interactions and molecular mechanisms between nAChRs and
      ligands will lead to a better translational and therapeutic operations and
      outcomes for the prevention and treatment of nicotine addiction and other chronic
      drug addictions in the brain's reward circuitry.

PMID- 30221882
TI  - Evaluation of Protective Impact of Algerian <I>Cuminum cyminum </I>L. and
      <I>Coriandrum sativum</I> L. Essential Oils on <I>Aspergillus flavus </I>Growth
      and Aflatoxin B<SUB>1</SUB> Production.
AB  - BACKGROUND AND OBJECTIVE: Aflatoxin B1 (AFB1) is a highly toxic and carcinogenic
      metabolite produced by Aspergillus species on food and agricultural commodities.
      The aim of this investigation was to evaluate the inhibition of growth
      Aspergillus flavus E73 (A. flavus E73) and AFB1 production by Cuminum cyminum L.
      (C. cyminum L.) and Coriandrum sativum L. (C. sativum L.) essential oils (EOs) as
      well their antioxidant and phytotoxicity activities. METHODOLOGY: The C. cyminum
      L. and C. sativum L. EOs were extracted by hydrodistillation. The chemical
      profile of EOs was identified by GC-MS, antifungal activity was assessed by
      poisoned food technique and in term Minimal Inhibitory Concentration (MIC) and
      minimal fungicidal concentration (MFC) and antiaflatoxin effect by broth medium.
      The antioxidant activity of EOs was determined by DPPH free radical scavenging
      assay, beta-carotene bleaching test and total phenolic content by Folin
      Ciocalteu. Phytotoxicity of C. cyminum L. and C. sativum L. EOs were determined
      for varieties of wheat. The results were analyzed by analysis of variance (one
      way ANOVA). RESULTS: The GS/MS analysis showed that the major components of C.
      cyminum L. EO were cuminaldehyde (65.98%), o-cymene (18.40%) and C. sativum L. EO
      was mainly consisted of linalool (78.86%). The results showed that both the EOs
      could inhibit the growth of A. flavus E73 in the range of 24.27-84.90% for C.
      cyminum and 15.09-65.00% for C. sativum. During antiaflatoxin investigation, the
      oils exhibited noticeable inhibition on dry mycelium weight and synthesis of AFB1
      by A. flavus E73. EOs of C. cyminum L. and C. sativum L. revealed complete
      inhibition of AFB1 at 1.25 and 1.5 mg mL-1, respectively. EOs exhibited
      inhibitory influence against some fungi. The IC50 values of C. cyminum L. and C.
      sativum L. EOs were 494.93 and 756.43 MUg mL-1, respectively, while, beta
      carotene/linoleic acid bleaching was 47.68 and 29.29% , respectively. Total
      phenolic content of C. cyminum L. and C. sativum L. were 10.66 and 6.2 MUg mg-1.
      Additionally, the EOs were non-phytotoxic on the two verities of wheat seeds.
      CONCLUSION: The C. cyminum L. and C. sativum L EOs could be good alternative to
      protect foods.

PMID- 30221883
TI  - Embryonic and Larvae of Endemic Celebes Rainbow Fish <I>Marosatherina
      ladigesi</I> (C.G.E.Ahl, 1936) (Atheriniformes: Telmatherinidae).
AB  - BACKGROUND AND OBJECTIVE: Marosatherina ladigesi is locally called the "beseng
      beseng' including endemic freshwater fish in South Sulawesi, Indonesia. The
      objective of this was to describe for the first time the development from eggs to
      the post flexion larval stage under controlled conditions and was to determine
      the developmental stages of embryonic and larvae of M. ladigesi. This
      consideration is possible to conduct breeding program of this species
      commercially and is suitable for commercial culture. MATERIAL AND METHODS: Brook
      stocks were reared for 5 months with fed twice daily with mixture of Daphnia sp.,
      Chironomus sp. and Culex sp. Water was substituted up to 50% each week.
      Artificial substrate from plastic rope was attached in the tank. The eggs were
      collected 6 h after laying on the substrate. The larvae were fed twice daily with
      infusoria, Daphnia sp. and Artemiasalina nauplii. Observations of embryonic
      development were performed every 6 h until the eggs hatched. Egg samples were
      observed with 5 eggs at a time. Larvae were observed at the ages of 0.3, 5, 7,
      10, 15, 20, 25 and 30 DAH. RESULTS: The process of embryonic development takes
      204 h after spawning (HAS) or 8.5 days after hatching (DAH). The cleavage stage
      is composed of 4-8 cell divisions that occur before 12 HAS, 16 cells formed at 12
      HAS and 32-64 cells formed at 24-30 HAS, cell multiplication occurs after 36 HAS.
      The morula stage is 42 HAS, the blastula stage occurs at 54-60 HAS, the gastrula
      stage occurs at 72 HAS, the neurula stage begins at 84 HAS and the segmentation
      stage occurs at 96 HAS. The segmentation stage shows already formed eye spots.
      The yolk stage lasted until 5 DAH, the free flexion stage occurred at 7 DAH, the
      flexion phase at 10 DAH and the post flexion stage at 15 DAH. The mouth was
      open65-78 HAS or 3 DAH and the yolk reserves were used for 5 DAH. CONCLUSION: M.
      ladigesi eggs are very adhesive and do not float and the eggs hatch to larvae at
      204 HAS or 8.5 DAH at 29+/-1 degrees C. This study revealed that the flexion
      stage occurred after 10 DAH and the post flexion stage after 15 DAH. The mouth
      was open after 65-78 h (3 DAH) and the yolk sac reserves were used for 5 DAH.

PMID- 30221885
TI  - Biological Activity of Local Entomopathogenic Nematodes from Two Different
      Origins Based on Various Temperatures.
AB  - BACKGROUND AND OBJECTIVE: Biological activity such as reproduction rate,
      viability and pathogenicity of local entomopathogenic nematodes (EPNs) are
      influenced by ecological factors, one of them is temperature. In order to prepare
      the biopesticides product, the study aimed to compare their production rate,
      viability and pathogenicity of EPNs from Semarang isolate and commercial
      biopesticide under various temperatures. MATERIALS AND METHODS: This study was
      designed by Completely Randomized Design one-way classification. Both EPNs were
      cultured in vivo condition with Tenebrio molitor larvae by white trap method. The
      reproduction rate of nematodes was calculated after 8 days of incubation and its
      viability test at six storage temperatures. The EPNs with the best viability was
      further tested for its pathogenicity on Macrotermes sp. The reproduction rate of
      nematodes were analyzed by using student's t-test, while one-way ANOVA was used
      to analyze the viability of EPNs, and pathogenicity of lethal dose value was
      calculated using Probit analysis. RESULTS: The findings showed that the
      reproduction rate on EPNs from Semarang isolate was significantly higher (p<0.05)
      than EPNs from commercial biopesticide. Various temperatures significantly
      affected the viability on both nematodes, but under LSD test (p<0.05) revealed
      that viability at storage of 21, 24 and 27 degrees C were not different of each
      other. CONCLUSION: The reproduction rate of EPNs from Semarang isolate was 35%
      higher than those originated from commercial biopesticide. The optimum viability
      of both EPNs was obtained at temperature ranged from 21-27 degrees C. The
      LD50value of EPNs from Semarang isolate was better than nematodes originated from
      commercial biopesticide.

PMID- 30221884
TI  - Body Weight Gain, Nutrients Degradability and Fermentation Rumen Characteristics
      of Boerka Goat Supplemented Green Concentrate Pellets (GCP) Based on Indigofera
      zollingeriana.
AB  - BACKGROUND AND OBJECTIVE: Indigofera zollingeriana leguminous have been known
      widely to have a concentrate feed characteristic due to its high nutrient
      contents (crude protein, vitamin and some mineral) and its highly dry matter (DM)
      digestibility. This study aimed to identify the effects body weight gain,
      nutrients degradability, fermentation rumen characteristics and blood metabolite
      of Boerka goat supplemented green concentrate pellets (GCP)based on Indigofera
      zollingeriana. MATERIALS AND METHODS: Twenty four male Boer x Kacang crossbreeds
      with age of approximately male phase to 6 months and average initial body weight
      (BW) 13+/-0.5 kg were used in feeding and degestion trials. The study was
      assigned according to randomized block design with four dietary treatments and
      six goats were allocated to one of four treatments in randomised block design.
      The animals feed was offered chopped fresh Brachiaria humidicola (ad libitum) and
      feed treatments were offered daily at 4.0% body weight (BW). RESULTS: The
      digestibility increased in line with the increasing proportion of I.
      zollingeriana in the green concentrate pellets (GCP). The tannin content of GCP
      seemed to not significantly impacted on feed intake. The daily body weight gain
      and efficiency of feed utilization increased as the proportion of I.
      zollingeriana GCP increased. Increasing of the proportion C. calotyhrsus in GCP
      affected the concentration of ammonia (NH3) and VFA of the rumen liquids of goat.
      CONCLUSION: Green concentrate pellets composing 90% I. zollingeriana gave the
      best results in term of daily body weight gain, feed intake, nutrient
      degradability, efficiency of feed utilization, rumen fermentation in Boerka
      goats.

PMID- 30221886
TI  - Screaming silences: lessons from the application of a new research framework.
AB  - BACKGROUND: The Silences Framework ( Serrant-Green 2011 ) originated from
      research exploring ethnicity, gender and sexual health decision-making, and
      provides a useful tool for researching underrepresented groups and topics. AIM:
      To present the lessons learned from the application of the Silences Framework in
      the context of a qualitative study exploring the experiences of people under the
      age of 60 recovering from a fragility hip fracture. DISCUSSION: The authors
      explore current conceptions of marginalisation in healthcare with reference to
      nursing research and provide practical tips for others interested in applying and
      further testing the framework. CONCLUSION: The framework is likely to be
      attractive to nurses as it is underpinned by core nursing values, such as
      advocacy-based action. It places participant and public voices at the centre of
      the research and resembles the familiar nursing process. The structure and
      flexibility it offers also makes it relevant for new and experienced researchers
      in a variety of contexts. IMPLICATIONS FOR PRACTICE: Critical analysis of the
      initial application of the Silences Framework in a different setting to the one
      in which it was developed indicates it offers a beneficial addition to the
      research toolkit. Its limited use to date means its relevance for nursing and
      potential for further development have not yet been fully established. It should
      be tested more widely and in other contexts.

PMID- 30221887
TI  - [Analysis of XPS in the Removal of Cr(VI) from Groundwater with rGO-nZVI].
AB  - Iron nanoparticles are widely used in heavy metal ions removal from water, but
      because of the characteristics of easily aggregation and transference in the
      groundwater, remediation effect was reduced. GO with a negative charge containing
      oxygen-containing functional groups on the surfaces of graphene, are widely used
      for the removal of heavy metal ions from water, but it has little on remediating
      hexavalent chromium (Cr2O2-7, CrO2-4) with negatively charged electrons.
      Therefore, rGO-nZVI was synthesized via liquid phase reduction method to overcome
      the aggregation and transference of FeO, changing the negative charged Cr2O2-7 or
      CrO2-4 to positive charged Cr3+. The material behavior characteristics of Cr(VI)
      removal were discussed. X-ray diffraction (XRD) and transmission electron
      microscopy (TEM) were used to test the prepared rGO-nZVI. Results indicated that
      nZVI was successfully loaded on the surface of GO, and the shape of the particles
      was approximate ball and the granular diameter ranged from 20 to 100 nm. Removal
      efficiency of Cr(VI) (40 mg.L-1) from water was nearly 100% within 24 h using rGO
      nZVI. X-ray photoelectron spectroscopy (XPS) analyses using the XPSPEAK41 program
      indicated that FeO firstly reduced negatively charged Cr(VI) to positively
      charged Cr(III) by providing electron, then the chromium in the solution can be
      removed as chromium hydroxide (Cr(OH)3) by a hydrolysis precipitation process. As
      the reaction progress, materials charges were changing, which benefited
      adsorpting Cr(VI). After 24 h reaction, the residual nZVI loading on rGO-nZVI
      remained, which showed the potential of sequentially remediating contamination.
      The results showed important theoretical value and practicability.

PMID- 30221888
TI  - [Study of Crystallinity Performance of Pretreated Bamboo Fibers Based on X-Ray
      Diffraction and NMR].
AB  - At present there are many methods to discuss the crystallinity of lignocellulose
      but scholars experts have different opinions about them. This study, with bamboo
      under the different pretreatment conditions, and with help of acid, alkali and
      glycerol uses X-ray diffraction and CP/MAS13NMR in order to make clear of the
      crystallinity of bamboo change characteristics, and measured the area length,
      spacing, crystal plane diffraction peak position, the crystallinity index and
      parameters and complete the comparison of crystalline cellulose and Gaussian
      function curve C - 4 area signal area. Results showed that crystalline overall
      increased significantly after pretreatment, 002 peak become sharp and offset to
      the direction of large angle for alkali pretreatment, 002 crystal width
      increases, crystalline spacing is smaller. CP/MAS13NMR is consisting with XRD,
      but calculated value is smaller. It proved that effective processing can
      effectively disrupted the recalcitrance of bamboo, and produce highly active
      cellulose in lignocelluloses' biomass ethanol production, that provide guidance
      to realize the lignocellulose bioconversion and effective utilization.

PMID- 30221889
TI  - [Study on Si-PIN and CdTe Detectors Used in Energy Dispersive X-Ray Fluorescence
      Measurements].
AB  - Semiconductor detector is widely used in energy dispersive X-ray fluorescence
      measurements due to its excellent performance. In this paper, Si-PIN and CdTe
      semiconductor detectors were studied, performances of the two detectors were
      compared in material properties, detection efficiency, energy resolution and
      other aspects. Focused on the performance of the detectors influenced by the
      thickness of detector sensitive area, energy of incident X-ray, shaping time of
      post-stage circuit, and analyzed the differences of energy spectrum caused by
      escape peaks and hole trailing. Aiming at the problem of incomplete hole
      collection in detector, a digital multi-channel analyzer (DMCA) based on FPGA
      with rise-time discriminator was designed, it could reduce the influence of hole
      trailing effectively and improve energy resolution. The experimentation results
      indicate that the detection efficiency of Si-PIN and CdTe is roughly equal when
      energy is below 15 keV while CdTe has much higher detection efficiency than Si
      PIN when energy is above 15 keV. The optimum forming time of the Si-PIN detector
      is about 10 MUs, and the CdTe detector is about 2.6 MUs, so the CdTe detector is
      more suitable for the high count rate condition. Si-PIN detector has better
      energy resolution than CdTe detector for different energy incident X-ray. CdTe
      detector has obvious hole tailing effect and the energy resolution of CdTe
      detector is significantly improved by using DMCA with rise-time discrimination.

PMID- 30221890
TI  - [On-Site Analysis of Heavy Metals in Water with Handheld X-Ray Fluorescence and
      Pre-Concentration Device without External Power Supply].
AB  - Currently, increasing importance has been attached to heavy metal pollution of
      water environment. In order to help geologist and environmentalist to obtain on
      site experimental data, there is an urgent need to develop portable analysis
      techniques of water quality, which can be used to give an timely and accurate
      assessment of water quality of the contaminated area with low cost and to monitor
      water environment conveniently in daily preventing and controlling work of water
      pollution. Based on adsorption with Purolite S930 chelating resin at pH 4 and
      thin-film sample preparation technique, a rapid and simple on-site-oriented
      analysis method of heavy metal ions, namely Mn, Fe, Ni, Cu, Zn and Pb in aqueous
      solutions, was developed utilizing a handheld energy-dispersive X-ray
      fluorescence in this paper. The correlation coefficients of the calibration
      curves were greater than 0.992 for all six metal ions, the lower limits of
      detection were between 5.8 and 18.6 MUg.L-1. Precision tests carried out on multi
      element mixed solutions showed that the relative standard deviations (RSD, n=10)
      were better than 15%. The method has been used on-site to analysis 21 water
      samples collected from different river or well sites near a mining area northeast
      China. Out of the five underground water samples one was found contaminated by Cu
      and Zn (Class III), one by Zn and Fe (Class II), and one by Fe(in between Class
      II to III). Surface water samples showed better qualities. But two out of the
      sixteen were found to be contaminated by Mn heavily (Class IV). Laboratory ICPMS
      was used to analyze the same samples. The results for Cu, Ni and Pb were
      coincident with the on-site data in general. But for Zn and Mn with higher
      concentrations, on-site data were lower than that by ICPMS. The reason for that
      might be the inclusion of the fine suspending particles in the samples by ICPMS.
      We conclude that the on-site data were effective. With the described method, an
      overall data acquisition time, including sampling, processing and measuring, can
      be within 12 hours for a batch of 10 samples. The pre-concentration device and
      the XRF instrument are both small, light, portable and can operate without
      external power supply. So, the method is suitable for on-site water sample
      analysis, especially in remote areas.

PMID- 30221891
TI  - Clinical and molecular prognostic factors in adrenocortical carcinomas.
AB  - INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare cancer, with an incidence
      less than 0.7-1.5 per 1 million people per year, with a poor prognosis. The
      overall survival (OS) depens on the ENSAT stage: in particular in metastatic ACC
      the OS varies between 10 and 20 months, with a 5-yrs survival around 10%. ACC
      present a different behaviour, probably due to a different biology. For these
      reason a careful prognostic classification is mandatory, in order to stratify the
      patients and purpose a specific management. EVIDENCE ACQUISITION: Prognostic
      factors can be divides in three groups: clinical factors (tumor stage, Age,
      hormone- related symptoms), pathological factor (Weiss score, mitotic count,
      Ki67,SF-1 and AVA2, P53, beta-catenin immunohistochemistry, resection status),
      molecular factor (chromosomal aberrations, methylation profile, altered gene
      expression and miRNA expression, gene mutations). EVIDENCE SYNTHESIS: The best
      way in order to stratify ACC patients and purpose the best therapeutic option is
      to combine clinical, pathological and molecular factors. CONCLUSIONS:
      Individualizing patients' prognosis and tumor biology appears as a necessary step
      for personalized medicine. In addition to tumor stage and tumor grade, the
      genomic classification may precise the risk stratification and thus help defining
      therapeutic strategy.

PMID- 30221892
TI  - Adrenocortical tumours: challenges and recent advances in diagnosis and
      treatment.

PMID- 30221893
TI  - [The Automatic Recognition and Detection of Sky-Subtraction Residual Componentin
      the Stellar Spectra].
AB  - The skylines, superimposing on the target spectrum as a main noise, will reduce
      the signal-to-noise ratio of the spectrum. If the spectrum still contains a large
      number of high strength skylight residuals after sky-subtraction processing, it
      will not be conducive to the follow-up analysis of the target spectrum. At
      present, the study on the automatic recognition of the abnormal sky-subtraction
      stellar spectra is limited in number. We can only find the abnormal sky
      subtraction spectra by manual inspection, and this will reduce the speed of
      detection. This paper analyzes the influence factors of sky-subtraction results
      and finds the characteristics of the abnormal sky-subtraction spectra. A simple
      and effective method is proposed to automatic recognize the abnormal sky
      subtraction stellar spectra which have been processed with the LAMOST Pipeline
      processing procedure and find the positions of the abnormal skylines. In this
      method, all the spectra are normalized first; the abnormal skyline is determined
      by detecting whether there exits any high strength skyline residuals which are
      similar to the emission line or absorption line. Finally, all the abnormal
      skyline positions in the spectra are obtained in this method. The experimental
      results with the LAMOST spectroscopic dataset show that this method can recognize
      the abnormal sky-subtraction spectra and find the abnormal skyline positions of
      different residual strength effectively. In addition, the method is simple and
      has high recognition efficiency, and can be applied to the automatic detection of
      abnormal sky-subtraction of large number of spectra.

PMID- 30221894
TI  - [Stellar Alpha Element Abundance Estimation Using LASSO Algorithm].
AB  - In this paper, a new method based on LASSO algorithm is studied for the
      estimation of stellar alpha element abundance. The information of alpha elements
      (O, Mg, Ca, Si, and Ti) of massive stars will help us to better understand the
      evolution of the galaxy. Presently the main method of determining the alpha
      element abundances from the low resolution spectra is the template matching
      method. However, it is difficult for us to optimize the algorithm parameters and
      the algorithm is sensitive to the noise. Thus, it is necessary to study the new
      method to determine the abundance. The experimental results show that the
      accuracy of LASSO algorithm on ELODIE spectra is 0.003 (0.078) dex. To explore
      the impact of the spectral resolution variation, we use ELODIE spectra to
      generate the spectral data sets with following resolutions: 42 000, 21 000, 10
      500, 4 200 and 2 100 by using the Gaussian convolution. The results of the LASSO
      algorithm on these data sets are 0.003 3 (0.078) dex, -0.05 (0.059) dex, -0.007
      (0.069) dex and -0.004 5 (0.067) dex, respectively. These results show that the
      LASSO algorithm is not sensitive to the change of the resolution. In order to
      verify the robustness of LASSO algorithm against the change of SNRs, we use
      ELODIE to generate the spectral data sets with following SNRs: 30, 25, 20, 15 and
      5. The results of LASSO algorithm on the above data sets are: -0.002 (0.076) dex,
      -0.090 (0.073) dex, 0.003 6 (0.075) dex, 0.007 6 (0.078) dex and -0.009 (0.080)
      dex, respectively. Thus, LASSO algorithm is not sensitive to the change of SNR.
      Therefore, the LASSO algorithm is suitable for low resolution and low SNR spectra
      such as LAMOST and SDSS spectra. The accuracy of Lasso algorithm on the SDSS
      spectra is 0.003 7 (0.097) dex, and the results of LASSO on globular and open
      clusters show good agreement with literature values (within 1sigma). Therefore,
      the LASSO algorithm can be used to estimate the alpha element abundances of
      stars.

PMID- 30221895
TI  - Lessons learned and learning curve of fenestrated and branched endografts.
AB  - Fenestrated and branched endovascular repair (F-BEVAR) has been increasingly used
      to treat patients with complex aortic aneurysms involving the renal-mesenteric
      arteries. As with any new procedure, there is a learning curve associated with
      mastering the technique. However, proficiency with deployment is only one aspect
      of the learning process, and ultimately, this curve is defined not by one quality
      parameter, but by patient selection, the performance of the entire team, the
      surgeons ability to adapt to unexpected events, and the durability of the repair.
      This article reviews the importance of novel training paradigms, learning curve,
      and factors affecting outcomes of complex endovascular aneurysm repair.

PMID- 30221896
TI  - [FBG Self-Chirped Based on an Sine-Structure].
AB  - Considerting that the uniform grating can be induced chirp effect under non
      uniform strain, a method of making chirp grating by uniform grating with the use
      of sine structure is proposed. The sine structure was designed as basal material
      while the fiber Bragg and grating was pasted in the strain non-uniform area of
      basal material. the strain it produced was introducied into FBG gate area by
      applying tensile load to achieve FBG produce chirp effect. FBG was made with
      multiple peaks and wide bandwidth of the chirp grating. The finite element
      software was used to simulate the strain of sine-structure under tensile loading
      to get strain contours of the sinusoidal structure in different positions; The
      experimental results showd that the bandwidth has been increased five times when
      the displacement load was up to 8 mm and the chirp grating reflection spectrum
      with multiple peaks; The transfer matrix method to reflection spectrum of chirp
      grating was combined for spectrum simulation reconstruction and the simulation
      spectrum spectrum trend was consistent with the experimental results. The chirp
      grating made in this method has an important application in complex strain field
      multiple parameters and achieving sense of temperature without compensation by
      the use of the bandwidth of the chirp grating at the same time.

PMID- 30221897
TI  - Influence of Dimethyl Sulfoxide as Processing Additive for Improving Efficiency
      of Polymer Solar Cells.
AB  - The effect of dimethyl sulfoxide (DMSO) doping concentration on the performance
      of polymer solar cells (PSCs) based on poly(3-hexylthiophene) (P3HT)?(6,6)-phenyl
      C60 butyric acid methyl ester (PCBM) as the active layer was investigated. The
      results suggest that the doping of DMSO can improve short-circuit current density
      (Jsc) and fill factor (FF) of the PSCs. The cell with 3% DMSO exhibits enhanced
      Jsc (7.88 mA.cm-2), and FF (55.5%). The optimized power conversion efficiency
      (PCE) arrived to 2.54%, which is 17% higher than that of the cell without DMSO
      doping. The Fourier Transform infrared spectroscopy (FTIR) is used to demonstrate
      the effect of DMSO doping into P3HT : PCBM on chemical properties. The presence
      of FTIR suggests that the chemical properties of P3HT and PCBM have no changes.
      To investigate the causes of the PCE improvement after addition of DMSO, an
      enhanced light harvesting and charge carriers transport properties of
      electroluminescence devices were observed by UV-Visible spectra and J-V
      characteristics. The absorption peaks of P3HT : PCBM : DMSO thin film show a
      distinguished red shift and strong absorption compared to P3HT : PCBM thin films
      in the visible light range. It was considered that the increase of the Jsc was
      supported by this phenomenon of UV-Visible absorption. The charge carrier
      mobility change of the P3HT : DMSO films is studied by employing the donor-only
      devices. The increased performance should be attributed to the enhanced charge
      carrier mobility and widened absorption spectra of P3HT : PCBM through doping
      DMSO.

PMID- 30221898
TI  - Fecal microbiota transplantation for recurrent Clostridium difficile infection:
      Experience, protocol, and results.
AB  - OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective therapy
      for recurrent Clostridium difficile infection (R-CDI). Despite its excellent
      efficacy, it is still not a routine procedure in most European centers. FMT has
      not been widely used in Spain to date. We describe our experience with FMT,
      including a novel approach based on oral fecal capsules. METHODS: We analyzed a
      prospectively recorded case series of patients with R-CDI treated with FMT at a
      single center (June 2014-July 2017). Primary outcome was defined as resolution of
      CDI without recurrence in a two-month period. FMT was administered via
      colonoscopy, nasojejunal tube, or oral capsules. All stool donors were rigorously
      screened. RESULTS: FMT was performed in 13 patients with R-CDI. Median age was
      75.0 years and 76.9% were females. Six FMT were performed via nasojejunal tube, 5
      via oral capsules, and 2 by colonoscopy. There were no procedure-related adverse
      events, except for bacteremia in one patient. During follow-up, R- CDI was
      observed in one patient at one month after FMT. The primary resolution rate was
      83.3% and the overall resolution rate was 91.7%. FMT by capsules achieved a 100%
      resolution rate, colonoscopy 100%, and nasojejunal tube 80.0%. CONCLUSIONS: In
      our cohort, FMT proved to be safe and effective, even in high risk patients. Oral
      administration in capsules also proved to be safe, well-tolerated, and highly
      effective for R-CDI. In our experience, the FMT capsule formulation seems
      feasible in the routine of a hospital. This administration method will allow FMT
      to be more widely used.

PMID- 30221899
TI  - Colistin resistance due to insertional inactivation of the mgrB in Klebsiella
      pneumoniae of clinical origin: First report from India.
AB  - OBJECTIVE: Mutations in mgrB, phoP/phoQ, pmrA, pmrB, pmrC, and crrABC regulatory
      systems have been found responsible for colistin resistance. The aim of our study
      was to investigate the role of alteration in mgrB gene and plasmid mediate mcr-1
      and mcr-2 genes as a source of colistin resistance in 17 non duplicate Klebsiella
      pneumoniae clinical isolates. METHODS: All isolates classified as resistant to
      colistin by VITEK 2 system (BioMerieux, Marcy I' Etoile, France) were included.
      Susceptibility to colistin was also determined by broth microdilution using
      breakpoints recommended by EUCAST (>2mg/L resistant; and <=2mg/L susceptible).
      PCR amplification of mgrB gene was performed and sequenced using specific
      primers. Presence of mcr-1 and mcr-2 was also investigated using PCR. RESULTS:
      PCR amplification of the mgrB gene of the 17 K.pneumoniae isolates revealed a
      larger (~1000bp) amplicon in three isolates when compared with the wild type mgrB
      ampiclon (250 bp). Sequencing of these amplicons showed that mgrB was disrupted
      by the insertion of ISKpn14, a IS element belonging to the IS1 family.
      Sequencing, of the 250 bp mgrB gene in the remaining 14 isolates revealed frame
      shift mutation after the second codon leading to a premature stop codon in only
      one isolate. CONCLUSIONS: The study showed that colistin resistance in 20% of the
      K. pneumoniae isolates was due to loss of function of mgrB. We describe for the
      first-time from India, insertional inactivation of mgrB by ISKpn14 inserted at
      different sites, responsible for colistin resistance.

PMID- 30221900
TI  - A young patient with fever after heart transplantation.

PMID- 30221901
TI  - [Hypertension diagnosis in patiens with HIV infection].

PMID- 30221902
TI  - [HIV-1 integrase inhibitor resistance among treatment naive patients in Gran
      Canaria, 2017].

PMID- 30221903
TI  - Investigation of N Deficiency in Cherry Trees Using Visible and Near-Infrared
      Spectra Part of the Spectrum in Field Condition.
AB  - This objective of the study was to develop a model for the determination of N
      deficiency in cherry trees using a combination of visible near infrared methods
      and spectro-radiometric measurement. In our experimental design, cherry seedlings
      were grown under various N deficiency conditions in nutrient-controlled
      containers. The reflectance values of plant leaves were measured using a spectro
      radiometer. Plant leaves samples were simultaneously collected. Their nutrient
      contents were determined in the laboratory. Afterwards, we performed a
      statistical comparison of the reflectance values. Sample analysis results
      established the significant wavelengths. Moreover, we received accurate
      regression models for predicting N deficiency in cherry leaves that were grown in
      nutrient solutions. Next, we verified the model validity by measuring the
      reflectance of the leaves collected from cherry orchards at various locations
      using a spectroradiometer. Nutrient deficiencies were calculated using the
      developed model, and then, the predicted and measured data were compared to
      evaluate model validity. From these results, we determined the wavelengths that
      yielded the most accurate results for N prediction, selected from the blue and
      green regions of the spectrum. We established that for N prediction in cherry
      trees, the simplest model can be created using 560 and 570 nm wavelengths.
      However, the evaluated model can be applicable only under certain conditions. We
      concluded that in order to develop a prediction method with sufficient
      application capacity, as well as the ability to assess nutritional and
      physiological characteristics, the ecology condition of the plant should be
      properly considered based on the model.

PMID- 30221904
TI  - Novel Variable Selection Method Based on Uninformative Variable Elimination and
      Ridge Extreme Learning Machine: CO Gas Concentration Retrieval Trial.
AB  - Variable selection is an essential part in spectroscopy analysis area. To
      overcome the problems of traditional interval selection methods, this paper
      proposed a novel variable selection and assessment method based on uninformative
      variable elimination (UVE) and ridge extreme learning machine (RELM) algorithms.
      Firstly, the UVE method was adopted to eliminate the uninformative wavelengths.
      Secondly, to solve the collinearity problem, RELM algorithm was adopted to
      replace the traditional modeling methods (PLS, BP neural network, etc.). Finally,
      the optimal combination of wavelength regions was selected by using feature
      selection path (FSP) plot and sparsity-error trade-off (SET) curve. The
      experiment results of CO gas concentration retrieval showed that (1) the UVE
      algorithm can select the most informative variables, which were the feature
      wavelengths of the CO gas transmittance spectrum; (2) the RELM algorithm has the
      advantage of rapid modeling, solving the collinearity problem, and high accuracy
      (the determined coefficient r of CO gas concentration retrieval can reach 0.995);
      (3) the FSP plot and SET curve were easy understanding, also intuitive to experts
      to find the best combination of wavelengths and extract useful domain knowledge.

PMID- 30221905
TI  - Predictive factors determining incomplete response to radioiodine therapy in
      patients with differentiated thyroid cancer.
AB  - BACKGROUND: Although differentiated thyroid cancer (DTC) has relatively favorable
      course, factors predicting the course of the disease are intensively searched.
      The aim of the study was to identify the clinical factors determining incomplete
      response to radioiodine therapy in patients with differentiated thyroid cancer.
      METHODS: We retrospectively analyzed 385 consecutive patients with DTC treated
      and followed-up at a single tertiary reference center. We investigated clinical
      factors detectable during first hospitalization 3-6 months following total
      thyroidectomy due to DTC, which may serve as prognostic factors determining
      response to DTC therapy in a long-term follow-up. RESULTS: Stimulated
      thyroglobulin (sTg) was the only parameter significantly correlated with the
      cumulative radioiodine activity (r=0.247, p<0.001). The need for repeated
      radioiodine administration (>=3 doses) was best predictable on the basis of sTg
      concentration assessed at the moment of qualification to radioiodine therapy
      (p=0.003). Predictive value of the sTg for incomplete response to radioiodine has
      been confirmed with the ROC curve analysis and the best proposed cut-off value
      was 8.17 ng/ml (sensitivity 55%, specificity 77%, positive predictive value
      42.1%, negative predictive value 84.7%); sTg over 8.17 ng/ml increases the risk
      of incomplete response to therapy 2.5-folds (p=0.002). CONCLUSIONS: sTg, assessed
      at the moment of qualification to radioiodine therapy, as the most important
      factor determining incomplete response to radioiodine therapy in patients with
      DTC, should be particularly taken into consideration in predicting the future
      course of the disease as well as treatment and follow-up planning. Radical
      thyroidectomy may help to increase the effectiveness of treatment.

PMID- 30221906
TI  - Evaluation of physiologic and abnormal glucose uptake in palatine tonsils:
      differential diagnostics with sequential dual-time-point 2-deoxy-2-[18F]fluoro-D
      glucose positron emission tomography/computed tomography examinations.
AB  - BACKGROUND: The aim of this article was to evaluate the usefulness of sequential
      dual- time-point 2-deoxy-2-[18F]fluoro-D-glucose positron emission
      tomography/computed tomography (DTP [18F]FDG PET/CT) in distinguishing
      physiologic, inflammatory and malignant palatine tonsils as difficult to
      differentiate in the oncological practice. METHODS: A total of 90 patients before
      the treatment underwent sequential DTP [18F]FDG PET/CT examinations. We analyzed
      104 structures in 90 patients: 31 physiologic tonsils, 28 histopathologically
      confirmed inflammatory tonsils of non-specified origin, 31 histopathologically
      confirmed palatine tonsils cancer and 14 non-malignant contralateral tonsils in
      patients with histopathologically confirmed unilateral palatine tonsil
      malignancy. Patients underwent sequential [18F]FDG PET/CT examinations at 60 and
      90min p.i. of the [18F]FDG. We analyzed the SUVmax and SUVmean values at 60 and
      90min p.i. changes over time and the Retention Index (RI-SUVmax). To find the
      predictive SUV value and the RI cut-off between physiology, inflammatory and
      malignancy, we used the ROC analysis. RESULTS: The average SUVmax values at 60
      and 90min p.i. within physiologic palatine tonsils were 1.36+/-0.26 and 1.31+/
      0.26, respectively, p>0.05. The average SUVmax values at 60 and 90min p.i. within
      inflammatory and malignant tonsils were 3.74+/-1.45, 3.80+/-1.47 (p>0.05) and
      5.19+/-2.19, 5.81+/-2.50 (p<0.05), respectively. The RI-SUVmax fluctuation over
      time were 5%+/-28% within physiologic, -4%+/-11% within contralateral non
      malignant tonsils in patients with one tonsil involved, 2%+/-11% within
      inflammatory and 13%+/-13% within malignant tonsils. CONCLUSIONS: The sequential
      dual-time-point [18F]FDG PET/CT examinations may increase the sensitivity and the
      specificity of the PET/CT method in differential palatine tonsils diagnosis.

PMID- 30221907
TI  - Comparison of post-therapeutic sequential 131I whole-body scans in the detection
      of metastatic thyroid cancer.
AB  - BACKGROUND: The aim was to compare the detect ability of 3 sequential 131I whole
      body scans (tri-WBS) on the second, third, and fourth day after 131I therapy for
      metastatic thyroid cancer. METHODS: Differentiated thyroid cancer patients who
      received oral high-dose 131I therapy underwent routinely tri-WBS on the second,
      third, and fourth day after total or near-total thyroidectomy in our hospital. We
      enrolled 137 patients with 261 tri-WBSs in this study between January 2015 and
      November 2017. The inclusion criteria was that at least one metastasis was found
      in the tri-WBS. We classified radioactive uptake of metastatic lesions by visual
      assessment into 3 grades: grade 0 = no uptake, grade 1= suspicious uptake, and
      grade 2 = definite uptake. The fourth day 131I WBS images were also compared with
      concurrent pre-therapeutic 99mTc-pertechnetate WBS images when available. We also
      analyzed the serum Tg levels of probably statistical difference in the patients
      with lymph node, lung, bone, and multiple metastasis when they underwent the
      first radioiodine ablation. RESULTS: A total of 722 metastatic accumulations were
      identified in the final decisions, including 293 lymph node metastases, 261
      nodular pulmonary metastases, 49 diffuse bilateral pulmonary metastases, 106 bone
      metastases, and 13 other metastases. The differences of intensity of uptake in
      sequential three day images were significant in visualization of lymph node
      metastasis (x2=124.432, p<0.001), nodular pulmonary metastasis (x2=160.334,
      p<0.001), diffuse bilateral pulmonary metastasis (x2=41.710, p<0.001), and bone
      metastasis (x2=22.118, p<0.001) in our study. Compared to the second day scans,
      the fourth day scans detected 87 (29.70%) more metastatic lymph nodes, 111
      (42.53%) more nodular pulmonary metastases, 26 (53.06%) more diffuse bilateral
      pulmonary metastases and 17 (16.95%) more bone metastases. The differences of
      intensity of uptake between 99mTc-pertechnetate WBS and the fourth day 131I WBS
      were significant in visualization of lymph node metastasis (x2=172.624, p<0.001),
      nodular pulmonary metastasis (x2 = 111.004, p<0.001), diffuse bilateral pulmonary
      metastasis (x2=17.400, p<0.001) and bone metastasis (x2=46.298, p<0.001). The
      means of RTg in the patients with only lymph node, lung, bone metastasis, and
      multiple metastases were 47.20, 76.58, 89.00, and 91.56, respectively. The
      differences of serum Tg levels in the patients with only lymph node, lung, bone
      matastasis, and multiple metastases were significant (x2=35.850, p<0.001).
      CONCLUSIONS: The detect ability of tri-WBS was significantly different even for
      consecutive three day images on the second, third, and fourth day after 131I
      therapy for metastatic thyroid cancer. There was a linear trend of increasing
      131I uptake from the second to fourth day 131I WBS. The pre-therapy 99mTc
      pertechnetate WBS demonstrated a poor ability to detect metastatic thyroid cancer
      compared to 131I WBS. There was an increasing trend of the means of RTg in
      patients with more extensive metastases.

PMID- 30221908
TI  - A Comparative Study on Hemp (Cannabis sativa) Essential Oil Extraction Using
      Traditional and Advanced Techniques.
AB  - A comparative study of Cannabis sativa (Hemp) essential constituents obtained by
      using Supercritical Fluid Extraction (SCFE), Steam Distillation (SD) and
      Hydrodistillation (HD) is presented here. The optimized extraction temperatures
      were 130,110 and 50 C for hydrodistillation, steam distillation and supercritical
      fluid extraction respectively. The essential oil of C. sativa was analyzed by
      using Gas chromatography mass spectrometry (GC-MS). A total of 33, 30 and 31
      components have been identified in HD, SD and SCFE respectively. Yield of
      essential oil using SCFE (0.039%) was more than HD (0.025%) and SD (0.035%)
      extraction respectively. The main component of sesquiterpenes obtained by
      hydrodistillation at 130 C with their percentages included caryophyllene
      (40.58%), trans-alpha-bergamotene (5.41%), humulene (10.97%), cis-beta-farnesene
      (8.53%) and monoterpenes included alpha-pinene (2.13%), d-limonene (6.46%), p
      cymol (0.65%) and cineole (2.58%) respectively. The main component of
      sesquiterpenes obtained by SD steam distillation at 110 C including caryophyllene
      (38.60%) trans-alpha-bergamotene (4.22%), humulene (10.26%), cis-beta-farnesene
      (6.67%) and monoterpenes included alpha-pinene (3.21%), d-limonene (7.07%), p
      cymol (2.59%) and cineole (3.88%) whereas the more percentages of major
      components were obtained by SCFE at 50 C included caryophyllene (44.31%), trans
      alpha-bergamotene (6.79%), humulene (11.97%) cis-beta-farnesene (9.71%) and
      monoterpenes included alpha-pinene (0.45%), d-limonene (2.13%) p-cymol (0.19%)
      and cineole (1.38 %) respectively. We found yield/efficiency, chemical
      composition, quality of the essential oils by supercritical fluid extraction
      superior in terms of modern, green, saving energy and a rapid approach as
      compared to traditional techniques.

PMID- 30221909
TI  - The Antioxidant Inhibition of Clove Effective Fraction on Lipid, Protein and
      Spectra Variation of LDL.
AB  - Oxidation of low density lipoprotein (LDL) has been considered as the critical
      factor which led to atherosclerosis (AS). Lipid and protein in LDL were oxidized
      to cause change of spectra during oxidation. Clove has been demonstrated to
      possess the strongest antioxidant capacity among 87 both medical and edible
      plants proclaimed by China. However, whether LDL oxidation is inhibited by clove?
      If so, whether it inhibits the oxidation of lipid and protein in LDL, and how
      does spectral characteristic of LDL change during oxidation when clove was added
      into LDL. Currently, these questions are still unclear. Therefore, the inhibition
      efficiency of the effective fraction from clove (EFC) on oxidation of LDL was
      studied by UV-Visible spectra and fluorescence spectra. The results indicated
      that EFC might effectively delay propagation of conjugated diene (CD) during LDL
      oxidation and postpone reaching maximum of its content. Likewise, it might
      inhibit cholesterol degradation, tryptophan (Trp) fluorescence quenching, lysine
      (Lys) residues from being modified, and lipofuscins from being generated in
      peroxidatic reaction among lipid and protein. Besides, EFC also might affect
      variation of UV-Visible spectra of LDL during oxidation. This study provides
      reference for future research and development of clove functional food inhibiting
      AS.

PMID- 30221910
TI  - Frailty beyond the clinical dimension: discussion about the underlying aspect of
      the social capital.
AB  - It is repeatedly advocated in the medical literature the need of reshaping the
      care process in order to better address the unmet clinical needs of the highly
      vulnerable and complex ageing population. In the past twenty years, frailty has
      assumed the role of an arising and independent geriatric condition, different
      from disability and multimorbidity. Frailty is highly prevalent in older persons.
      The proper management of frailty relies on the accurate collection and
      interpretation of a wide spectrum of information about the health status of the
      individual. However, the optimal intervention plan cannot be correctly designed
      and implemented without the evaluation of the social characteristics of the frail
      older person. Unfortunately, this aspect has frequently been overlooked and
      research is still lagging on the topic. The main scope of this review is to
      present current evidence and propose possible axes of investigation in this
      field.

PMID- 30221911
TI  - Alcoholic liver fibrosis: detection and treatment.
AB  - Alcohol consumption is one of the main risks to public health. Alcohol Use
      Disorders (AUDs) cause 80% of hepatotoxic deaths, and approximately 50% of
      cirrhosis is alcoholrelated. The acceptable daily intake (ADI) for ethanol is 2.6
      g/day, deduced from morbidity and mortality rates due to liver fibrosis. The
      relative risk of cirrhosis increases significantly for doses above 60 g/day for
      men and 20 g/day for women over a period of around 10 years. Twenty to 40% of
      steatosis cases will evolve into steatohepatitis / steatofibrosis, and 8 to 20%
      will evolve directly into liver cirrhosis. About 20 to 40% of steatohepatitis
      cases will evolve into cirrhosis, and 4 to 5% into hepatocellular carcinoma. This
      cascade of events evolves in 5 to 40 years, with the temporal variability caused
      by the subjects' genetic patterns and associated risk / comorbidity factors.
      Steatohepatitis should be considered "the rate limiting step": usually, it can be
      resolved through abstinence, although for some patients, once this situation
      develops, it is not substantially modified by abstention and there is a risk of
      fibrotic evolution. Early detection of fibrosis, obtained by hepatic
      elastography, is a crucial step in patients with AUDs. Such strategy allows
      patients to be included in a detoxification program in order to achieve
      abstention. Drugs such as silybin, metadoxine, and adenosylmethionine can be
      used. Oher drugs, with promising antifibrotic effects, are currently under study.
      In this review, we discuss clinical and pathogenetic aspects of alcoholrelated
      liver fibrosis and present and future strategies to prevent cirrhosis.

PMID- 30221912
TI  - Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a
      randomized clinical study.
AB  - BACKGROUND: The manipulation of gut microbiota via administration of probiotics
      has been proposed as a potential strategy for the treatment of non-alcoholic
      fatty liver disease (NAFLD). Hence, we performed a double-blind single center
      randomized placebo-controlled trial (RCT) to evaluate the efficacy of co
      administration of probiotics with omega-3 vs. placebo in type-2 diabetic patients
      with NAFLD. METHODS: A total of 48 patients met the criteria for inclusion. They
      were randomly assigned to receive "Symbiter Omega" combination of probiotic
      biomass supplemented with flax and wheat germ oil (250 mg of each, concentration
      of omega-3 fatty acids 1-5%) or placebo for 8-weeks. The primary main outcomes
      were the change in fatty liver index (FLI) and liver stiffness (LS) measured by
      Shear Wave Elastography (SWE). Secondary outcomes were the changes in
      transaminases level, serum lipids and cytokines levels. RESULTS: In probiotic
      omega group, FLI significantly decreased from 83.53+/-2.60 to 76.26+/-2.96
      (p<0.001) while no significant changes were observed in the placebo group
      (82.86+/-2.45 to 81.09+/-2.84; p=0.156). Changes of LS in both groups were
      insignificant. Analysis of secondary outcomes showed that the co-administration
      of probiotics with omega-3 lead to significant reduction of serum gamma-glutamyl
      transpeptidase, triglycerides, and total cholesterol. Chronic systemic
      inflammatory markers after intervention decrease significantly only in Symbiter
      Omega group: IL- 1beta (p=0.029), TNF-alpha (p<0.001), IL-8 (p=0.029), IL-6
      (p=0.003), and INF-gamma (p=0.016). CONCLUSIONS: Co-administration of a live
      multi-strain probiotic mixture with omega-3 fatty acids once daily for 8 weeks to
      patients with NAFLD can reduce liver fat, improve serum lipids, metabolic
      profile, and reduce chronic systemic inflammatory state.

PMID- 30221913
TI  - Four Evidence-Based Communication Strategies to Enhance Patient Care.

PMID- 30221914
TI  - Physician-Patient Communication: A Family Medicine Strength.

PMID- 30221915
TI  - 10 Ways to Keep Your Quality Improvement Team Motivated.

PMID- 30221916
TI  - How to Have a Good Goodbye.

PMID- 30221917
TI  - How to Excel at Access -- and Why It Matters.

PMID- 30221918
TI  - The Case for Medical Chaperones.

PMID- 30221919
TI  - How Service Agreements Can Improve Referrals and Shrink the Medical Neighborhood.

PMID- 30221920
TI  - Versatile and Scalable Strategy To Grow Sol-Gel Derived 2H-MoS2 Thin Films with
      Superior Electronic Properties: A Memristive Case.
AB  - Transition metal dichalcogenides, such as molybdenum disulfide (MoS2), show
      peculiar chemical/physical properties that enable their use in applications
      ranging from micro- and nano-optoelectronics to surface catalysis, gas and light
      detection, and energy harvesting/production. One main limitation to fully harness
      the potential of MoS2 is given by the lack of scalable and low environmental
      impact synthesis of MoS2 films with high uniformity, hence setting a significant
      challenge for industrial applications. In this work, we develop a versatile and
      scalable sol-gel-derived MoS2 film fabrication by spin coating deposition of an
      aqueous sol on different technologically relevant, flexible substrates with
      annealing at low temperatures (300  degrees C) and without the need of
      sulfurization and/or supply of hydrogen as compared to cutting-edge techniques.
      The electronic and physical properties of the MoS2 thin films were extensively
      investigated by means of surface spectroscopy and structural characterization
      techniques. Spatially homogenous nanocrystalline 2H-MoS2 thin films were obtained
      exhibiting high chemical purity and excellent electronic properties such as an
      energy band gap of 1.35 eV in agreement with the 2H phase of the MoS2, and a
      density of states that corresponds to the n-type character expected for high
      quality 2H-MoS2. The potential use of sol-gel-grown MoS2 as the candidate
      material for electronic applications was tested via electrical characterization
      and demonstrated via the reversible switching in resistivity typical for
      memristors with a measured ON-OFF ratio >=102. The obtained results highlight
      that the novel low-cost fabrication method has a great potential to promote the
      use of high-quality MoS2 in technological and industrial-relevant scalable
      applications.

PMID- 30221921
TI  - Correlation between Distribution of Polymer Orientation and Cell Structure in
      Organic Photovoltaics.
AB  - The backbone orientation of semiconducting polymers is one of the important
      structural factors that determines the charge transport and thus the performance
      of optoelectronic devices. Here, we study two sets of thiophene-thiazolothiazole
      polymers, which primarily form edge-on and face-on orientations, termed "edge-on
      polymers" and "face-on-polymers", respectively; both orientation types co-exist
      in their polymer/fullerene blend films. Interestingly, we find that the
      dependence of the photoactive layer thickness on the fill factor in the
      photovoltaic cells, with the inverted and conventional structures, is quite
      distinct in the edge-on-polymer; however, this is not evident in the face-on
      polymers. An in-depth study by grazing incidence X-ray diffraction analysis
      reveals that the face-on/edge-on ratio is unevenly distributed through the film
      thickness in the edge-on-polymers, while it is evenly distributed in the face-on
      polymers. The difference in the distribution of the backbone orientation
      correlates with the difference in the thickness dependence on the fill factor. We
      thus propose that the distribution of the backbone orientation is an important
      factor to understand the performance of polymer-based photovoltaic cells and that
      the cell structure should be carefully selected by considering the distribution
      for maximizing the performance.

PMID- 30221922
TI  - Stable and Reversible Triphenylphosphine-Based n-Type Doping Technique for
      Molybdenum Disulfide (MoS2).
AB  - A highly stable and reversible n-type doping technique for molybdenum disulfide
      (MoS2) transistors and photodetectors is developed in this study. This doping
      technique is based on triphenylphosphine (PPh3) and significantly improves the
      performance of MoS2 transistor and photodetector devices in terms of the on/off
      current ratio (8.72 * 104 -> 8.70 * 105), mobility (12.1 -> 241 cm2/V.s), and
      photoresponsivity ( R) (2.77 * 103 -> 3.92 * 105 A/W). The range of doping
      concentrations is broadly distributed between 1.56 * 1011 and 9.75 * 1012 cm-2
      and is easily controlled by adjusting the temperature at which the PPh3 layer is
      formed. In addition, this doping technique provides two interesting properties
      that have not been reported for previous molecular doping techniques: (i) high
      stability leading to small variations in device performance after exposure to air
      for 14 days (on-current: 1.34% and photoresponsivity: 1.58%) and (ii)
      reversibility enabling the repetitive formation and removal of PPh3 molecules
      (doping and dedoping).

PMID- 30221924
TI  - Passive Antifrosting Surfaces Using Microscopic Ice Patterns.
AB  - Despite exceptional recent advances in tailoring the wettability of surfaces, to
      date, no engineered surface can passively suppress the in-plane growth of frost
      that invariably occurs in humid, subfreezing environments. Here, we show that up
      to 90% of a surface can exhibit passive antifrosting by using chemical or
      physical wettability patterns to template "ice stripes" across the surface. As
      ice exhibits a depressed vapor pressure relative to liquid water, these
      sacrificial ice stripes siphon the supersaturated water vapor to keep the
      intermediate surface areas dry from dew and frost. Further, we show that when
      these sacrificial ice stripes are elevated atop microfins, they diffusively
      coarsen in a suspended state above the surface. The suspended state of the
      coarsening ice results in a diffusive growth rate an order of magnitude slower
      than frost coarsening directly on a solid substrate and should also minimize its
      adhesive strength to the surface.

PMID- 30221923
TI  - The Spastic Paraplegia-Associated Phospholipase DDHD1 Is a Primary Brain
      Phosphatidylinositol Lipase.
AB  - Deleterious mutations in the serine hydrolase DDHD domain containing 1 (DDHD1)
      cause the SPG28 subtype of the neurological disease hereditary spastic paraplegia
      (HSP), which is characterized by axonal neuropathy and gait impairments. DDHD1
      has been shown to display PLA1-type phospholipase activity with a preference for
      phosphatidic acid. However, the endogenous lipid pathways regulated by DDHD1 in
      vivo remain poorly understood. Here we use a combination of untargeted and
      targeted metabolomics to compare the lipid content of brain tissue from DDHD1+/+
      and DDHD1-/- mice, revealing that DDHD1 inactivation causes a substantial
      decrease in the level of polyunsaturated lysophosphatidylinositol (LPI) lipids
      and a corresponding increase in the level of phosphatidylinositol (PI) lipids.
      Levels of other phospholipids were mostly unchanged, with the exception of
      decreases in the levels of select polyunsaturated lysophosphatidylserine (LPS)
      and lysophosphatidylcholine lipids and a striking remodeling of PI phosphates
      (e.g., PIP and PIP2) in DDHD1-/- brain tissue. Biochemical assays confirmed that
      DDHD1 hydrolyzes PI/PS to LPI/LPS with sn-1 selectivity and accounts for a
      substantial fraction of the PI/PS lipase activity in mouse brain tissue. These
      data indicate that DDHD1 is a principal regulator of bioactive LPI and other
      lysophospholipids, as well as PI phosphates, in the mammalian nervous system,
      pointing to a potential role for these lipid pathways in HSP.

PMID- 30221925
TI  - Diphenylethylenediamine-Based Potent Anionophores: Transmembrane Chloride Ion
      Transport and Apoptosis Inducing Activities.
AB  - Synthetic anion transporters have been recognized as one of the potential
      therapeutic agents for the treatment of diseases including cystic fibrosis,
      myotonia, and epilepsy that originate due to the malfunctioning of natural Cl-
      ion transport systems. Recent studies showed that the synthetic Cl- ion
      transporters can also disrupt cellular ion-homeostasis and induce apoptosis in
      cancer cell lines, leading to a revived attention for synthetic Cl- ion
      transporters. Herein, we report the development of conformationally controlled
      1,2-diphenylethylenediamine-based bis(thiourea) derivatives as a new class of
      selective Cl- ion carrier. The strong Cl- ion binding properties ( Kd = 3.87-6.66
      mM) of the bis(thiourea) derivatives of diamine-based compounds correlate well
      with their transmembrane anion transport activities (EC50 = 2.09-4.15 nM). The
      transport of Cl- ions via Cl-/NO3- antiport mechanism was confirmed for the most
      active molecule. Perturbation of Cl- ion homeostasis by this anion carrier
      induces cell death by promoting the caspase-mediated intrinsic pathway of
      apoptosis.

PMID- 30221926
TI  - Anion-Substitution-Induced Nonrigid Variation of Band Structure in SrNbO3- xN x
      (0 <= x <= 1) Epitaxial Thin Films.
AB  - Pervoskite oxynitrides exhibit rich functionalities such as colossal
      magnetoresistance and high photocatalytic activity. The wide tunability of
      physical properties by the N/O ratio makes perovskite oxynitrides promising as
      optical and electrical materials. However, composition-dependent variation of the
      band structure, especially under partially substituted composition, is not yet
      well understood. In this study, we quantitatively analyzed the composition
      dependent variation of band structure of a series of SrNbO3- xN x (0 <= x <=
      1.02) epitaxial thin films. Electrical conductivity decreased along with the
      increase of N content x as a result of an increase in Nb valence from 4+ to 5+.
      Optical measurements revealed that the N 2p band is formed at a critical
      composition between 0.07 < x < 0.38, which induces charge-transfer transition
      (CTT) in the visible-light region. These variations in the band structure were
      explained by first-principles calculations. However, the CTT energy slightly
      increased at higher N contents (i.e., lower carrier density) on contrary to the
      expectation based on the rigid-band-like shift of the Fermi level, which suggests
      a complex combination of the following band-shifting effects induced by N
      substitution: whereas (1) reduction of the Burstein-Moss effect causes CTT energy
      reduction, (2) enhancement of hybridization between Nb 4d and N 2p orbitals
      and/or (3) suppression of many-body effects enlarge the band gap energy at larger
      N content. The band structure variation in perovskite oxynitride as presently
      elucidated would be a guidepost for future material design.

PMID- 30221927
TI  - Enhanced Radiation Shielding with Conformal Light-Weight Nanoparticle-Polymer
      Composite.
AB  - This article reports a new property enabled by nanoparticles, where bismuth
      nanoparticles added in a polymer matrix can block X-ray radiation several times
      more efficient than microparticles at the same mass ratio. Bismuth nanoparticles
      are made with cellulose nanofibers and dispersed evenly into a polymer. A four
      time reduction in the mass of bismuth material is identified at 2% mass ratio
      when nanoparticles (5 nm in diameter) are used in composite to shield a given
      flux and energy of radiation, in relative to those of microparticles (5 MUm
      diameter). The enhancement in radiation shielding is primarily attributed to
      close packing of nanoparticles normal to incoming X-ray direction, which is
      enabled by strong affinity of nanoparticles to interstitial space of cellulose
      nanofibers and even distribution of nanoparticles inside polymer. Given its low
      cost, light weight, and structure conformability, bismuth nanoparticle-polymer
      composite will find its use in a wide range of fields related to personal
      radiation protection.

PMID- 30221928
TI  - In Situ Molecular-Level Observation of Methanol Catalysis at the Water-Graphite
      Interface.
AB  - Methanol occupies a central role in chemical synthesis and is considered an ideal
      candidate for cleaner fuel storage and transportation. It can be catalyzed from
      water and volatile organic compounds, such as carbon dioxide, thereby offering an
      attractive solution for reducing carbon emissions. However, molecular-level
      experimental observations of the catalytic process are scarce, and most existing
      catalysts tend to rely on empirically optimized, expensive, and complex
      nanocomposite materials. This lack of molecular-level insights has precluded the
      development of simpler, more cost-effective alternatives. Here, we show that
      graphite immersed in ultrapure water is able to spontaneously catalyze methanol
      from volatile organic compounds in ambient conditions. Using single-molecule
      resolution atomic force microscopy (AFM) in liquid, we directly observe the
      formation and evolution of methanol-water nanostructures at the surface of
      graphite. These molecularly ordered structures nucleate near catalytically active
      surface features, such as atomic step edges, and grow progressively as further
      methanol is being catalyzed. Complementary nuclear magnetic resonance analysis of
      the liquid confirms the formation of methanol and quantifies its concentration.
      We also show that electric fields significantly enhance the catalysis rate, even
      when as small as that induced by the natural surface potential of the silicon AFM
      tip. These findings could have a significant impact on the development of organic
      catalysts and on the function of nanoscale carbon devices.

PMID- 30221929
TI  - Collision-Induced Unfolding of Partially Metalated Metallothionein-2A: Tracking
      Unfolding Reactions of Gas-Phase Ions.
AB  - Metallothioneins (MTs) constitute a group of intrinsically disordered proteins
      that exhibit extreme diversity in structure, biological functionality, and metal
      ion specificity. Structures of coordinatively saturated metalated MTs have been
      extensively studied, but very limited structural information for the partially
      metalated MTs exists. Here, the conformational preferences from partial
      metalation of rabbit metallothionein-2A (MT) by Cd2+, Zn2+, and Ag+ are studied
      using nanoelectrospray ionization ion mobility mass spectrometry. We also employ
      collision-induced unfolding to probe differences in the gas-phase stabilities of
      these partially metalated MTs. Our results show that despite their similar ion
      mobility profiles, Cd4-MT, Zn4-MT, Ag4-MT, and Ag6-MT differ dramatically in
      their gas-phase stabilities. Furthermore, the sequential addition of each Cd2+
      and Zn2+ ion results in the incremental stabilization of unique unfolding
      intermediates.

PMID- 30221930
TI  - Reduced Graphene Oxide-Anchored Manganese Hexacyanoferrate with Low Interstitial
      H2O for Superior Sodium-Ion Batteries.
AB  - Low-cost manganese hexacyanoferrate (NMHCF) possesses many favorable advantages
      including high theoretical capacity, ease of preparation, and robust open
      channels that enable faster Na+ diffusion kinetics. However, high lattice water
      and low electronic conductivity are the main bottlenecks to their pragmatic
      realization. Here, we present a strategy by anchoring NMHCF on reduced graphene
      oxide (RGO) to alleviate these problems, featuring a specific discharge capacity
      of 161/121 mA h g-1 at a current density of 20/200 mA g-1. Moreover, the
      sodiation process is well revealed by ex situ X-ray diffraction, EIS and Car
      Parrinello molecular dynamics simulations. At a rate of 20 mA g-1, the hard
      carbon//NMHCF/RGO full cell affords a stable discharge capacity of 84 mA h g-1
      (based on the weights of cathode mass) over 50 cycles, thus highlighting
      NMHCF/RGO an alternative cathode for sodium-ion batteries.

PMID- 30221931
TI  - Switchable Fluorophores for Single-Molecule Localization Microscopy.
AB  - The past decade has witnessed an explosion in the use of super-resolution
      fluorescence microscopy methods in biology and other fields. Single-molecule
      localization microscopy (SMLM) is one of the most widespread of these methods and
      owes its success in large part to the ability to control the on-off state of
      fluorophores through various chemical, photochemical, or binding-unbinding
      mechanisms. We provide here a comprehensive overview of switchable fluorophores
      in SMLM including a detailed review of all major classes of SMLM fluorophores,
      and we also address strategies for labeling specimens, considerations for
      multichannel and live-cell imaging, potential pitfalls, and areas for future
      development.

PMID- 30221932
TI  - Multiplex On-Bead Isotope Dimethyl Labeling Coupled with Liquid Chromatography
      High-Resolution Mass Spectrometry for Quantitative Analysis of Sulfonamides in
      Estuarine Ice.
AB  - A multiplex-on-bead-isotope-dimethyl-labeling method was developed for the
      quantitative analysis of sulfonamides (SAs) in environmental water samples by
      liquid chromatography-high-resolution mass spectrometry (LC-HRMS). In this
      method, five samples could be labeled in parallel with different isotope reagents
      and quantified in a single LC-HRMS analysis. Magnetic solid-phase extraction
      (MSPE) was employed in the sample preparation to concentrate the trace-level
      analytes by using lab-synthesized magnetic carbon nanospheres (MCNSs). After the
      analytes were captured on the MCNSs, the isotope labeling was performed directly
      by dispersing the MCNSs in the reaction buffer (on-bead labeling). The
      experimental conditions for MSPE and labeling were systematically investigated.
      For the tested 12 SAs, a labeling efficiency of over 99% could be achieved within
      20 min. The LC-HRMS separation, including equilibration, could be achieved in 6
      min. By combining MSPE (enriched 200-fold), multiplex on-bead dimethyl labeling,
      and LC-HRMS, all the tested SAs could be reliably quantified with limits of
      detection (LODs) of 0.1-5 ng/L. This method was verified using fortified pond
      water spiked with 12 SAs (0.01-5 MUg/L), and accuracies of 81-106% were achieved
      with good reproducibility (RSD < 10%, n = 3), which confirmed its applicability
      in real-sample analysis. With this method, ice samples collected at the estuary
      of the Daliao River in northeast China were analyzed; nine SAs (sulfanilamide,
      sulfapyridine, sulfamethazine, sulfamethizole, sulfachloropyridazine,
      sulfamethoxypyridazine, sulfameter, sulfathiazole, and sulfisoxazole) were
      detected at concentrations of 0-85 ng/L, and the total concentrations were in the
      range of 185-402 ng/L with a median value of 274 ng/L.

PMID- 30221933
TI  - Targeting Neuroinflammation as a Therapeutic Strategy for Alzheimer's Disease:
      Mechanisms, Drug Candidates, and New Opportunities.
AB  - Alzheimer's disease is a progressive neurodegenerative disease, and its incidence
      is expected to increase owing to the aging population worldwide. Current
      therapies merely provide symptomatic relief. Therefore, interventions for AD that
      delay the disease onset or progression are urgently required. Recent genomics and
      functional studies suggest that immune/inflammatory pathways are involved in the
      pathogenesis of AD. Although many anti-inflammatory drug candidates have
      undergone clinical trials, most have failed. This might be because of our limited
      understanding of the pathological mechanisms of neuroinflammation in AD. However,
      recent advances in the understanding of immune/inflammatory pathways in AD and
      their regulatory mechanisms could open up new avenues for drug development
      targeting neuroinflammation. In this Review, we discuss the mechanisms and status
      of different anti-inflammatory drug candidates for AD that have undergone or are
      undergoing clinical trials and explore new opportunities for targeting
      neuroinflammation in AD drug development.

PMID- 30221934
TI  - Cr(VI) Effect on Tc-99 Removal from Hanford Low-Activity Waste Simulant by
      Ferrous Hydroxide.
AB  - Here, Cr(VI) effects on Tc-immobilization by Fe(OH)2(s) are investigated while
      assessing Fe(OH)2(s) as a potential treatment method for Hanford low-activity
      waste destined for vitrification. Batch studies using simulated low-activity
      waste indicate that Tc(VII) and Cr(VI) removal is contingent on reduction to
      Tc(IV) and Cr(III). Furthermore, complete removal of both Cr and Tc depends on
      the amount of Fe(OH)2(s) present, where complete Cr and Tc removal requires more
      Fe(OH)2(s) (~200 g/L of simulant), than removing Cr alone (~50 g/L of simulant).
      XRD analysis suggests that Fe(OH)2(s) reaction and transformation in the simulant
      produces mostly goethite (alpha-FeOOH), where Fe(OH)2(s) transformation to
      goethite rather than magnetite is likely due to the simulant chemistry, which
      includes high levels of nitrite and other constituents. Once reduced, a fraction
      of Cr(III) and Tc(IV) substitute for octahedral Fe(III) within the goethite
      crystal lattice as supported by XPS, XANES, and/or EXAFS results. The remaining
      Cr(III) forms oxide and/or hydroxide phases, whereas Tc(IV) not fully
      incorporated into goethite persists as either adsorbed or partially incorporated
      Tc(IV)-oxide species. As such, to fully incorporate Tc(IV) into the goethite
      crystal structure, additional Fe(OH)2(s) (>200 g/L of simulant) may be required.

PMID- 30221935
TI  - Inhibition of p53-Murine Double Minute 2 (MDM2) Interactions with 3,3'
      Spirocyclopentene Oxindole Derivatives.
AB  - 3,3'-Spirocyclopentene oxindoles structurally related to Wang's spiropyrrolidine
      oxindoles have been highlighted as a new class of antiproliferative agents
      against cancer cell lines with wild-type p53 status (IC50 up to 0.96 MUM on SJSA
      1 and 2.9 MUM in HCT116 p53-wt). Inhibition of the MDM2-p53 interactions has been
      demonstrated through in vitro HTRF assays (IC50 up to 3.1 nM), while Western blot
      analysis showed activation of p53 selectively in HCT116 cancer cell lines with
      wild-type p53.

PMID- 30221936
TI  - Molecular Recognition of Methionine-Terminated Peptides by Cucurbit[8]uril.
AB  - This Article describes the molecular recognition of peptides containing an N
      terminal methionine (Met) by the synthetic receptor cucurbit[8]uril (Q8) in
      aqueous solution and with submicromolar affinity. Prior work established that Q8
      binds with high affinity to peptides containing aromatic amino acids, either by
      simultaneous binding of two aromatic residues, one from each of two different
      peptides, or by simultaneous binding of an aromatic residue and its immediate
      neighbor on the same peptide. The additional binding interface of two neighboring
      residues suggested the possibility of targeting nonaromatic peptides, which have
      thus far bound only weakly to synthetic receptors. A peptide library designed to
      test this hypothesis was synthesized and screened qualitatively for Q8 binding
      using a fluorescent indicator displacement assay. The large fluorescence response
      observed for several Met-terminated peptides suggested strong binding, which was
      confirmed quantitatively by the determination of submicromolar equilibrium
      dissociation constant values for Q8 binding to MLA, MYA, and MFA using isothermal
      titration calorimetry (ITC). This discovery of high affinity binding to Met
      terminated peptides and, more generally, to nonaromatic peptides prompted a
      detailed investigation of the determinants of binding in this system using ITC,
      electrospray ionization mass spectrometry, and 1H NMR spectroscopy for 25
      purified peptides. The studies establish the sequence determinants required for
      high-affinity binding of Met-terminated peptides and demonstrate that cucurbit[
      n]uril-mediated peptide recognition does not require an aromatic residue for high
      affinity. These results, combined with the known ability of cucurbit[ n]urils to
      target N-termini and disordered loops in folded proteins, suggest that Q8 could
      be used to target unmodified, Met-terminated proteins.

PMID- 30221937
TI  - Multiphoton Ionization of One-Electron Relativistic Diatomic Quasimolecules in
      Strong Laser Fields.
AB  - We perform a theoretical and computational study of relativistic one-electron
      homonuclear diatomic quasimolecules subject to strong electromagnetic fields
      linearly polarized along the molecular axis. Several quasimolecules with the
      nuclear charges 1-92 and appropriately scaled internuclear distances and field
      parameters are used in the calculations. The time-dependent Dirac equation is
      solved with the help of the generalized pseudospectral method in prolate
      spheroidal coordinates. We have found that employing this coordinate system makes
      it possible to avoid emergence of spurious states, which usually show up when
      solving the Dirac equation numerically. For lower carrier frequencies,
      interaction with the driving field is described within the dipole approximation.
      Relativistic effects in the multiphoton ionization probabilities are investigated
      with respect to the internuclear distance in the quasimolecule. For higher
      frequencies, the interaction with the field is described beyond the dipole
      approximation. Nondipole effects in the ionization probability are discussed.

PMID- 30221938
TI  - Correction to Rapid Sampling of Hydrogen Bond Networks for Computational Protein
      Design.

PMID- 30221939
TI  - Impact of Carbonate Ions on the Synthesis of ThSiO4 under Hydrothermal
      Conditions.
AB  - Multiparametric study of the hydrothermal synthesis of thorite, ThSiO4, was
      performed with the aim to determine the most efficient conditions to form single
      phase thorite samples. Among the experimental parameters investigated,
      temperature of the hydrothermal process, concentration of carbonate ions, thorium
      and silicon reactants, and pH of the reactive media significantly affect the
      composition of the final system obtained. Single phase samples of ThSiO4 were
      prepared in weakly basic reactive media and at temperatures over 150  degrees C,
      for thorium and silicate concentrations higher than 8 * 10-3 mol L-1 and
      carbonate concentrations of at least 8 * 10-2 mol L-1. Although the synthesis of
      thorite in carbonate media was already described in the literature, this study
      gives new insights to explain the key role of carbonate ions in the preparation
      of thorite. Especially, beyond their simple role of pH buffer, carbonate ions are
      involved in the formation of thorium-carbonate complexes at high pH, increasing
      the apparent solubility of thorium in weakly basic media. The presence of
      carbonate ions has an important impact not only on the domain of formation of
      thorite but also on the morphology of the silicate phase.

PMID- 30221940
TI  - Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A
      (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer
      Chemotherapy.
AB  - Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify
      cancer stem-like cells. The three ALDH1A isoforms have all been individually
      implicated in cancer stem-like cells and in chemoresistance; however, which
      isoform is preferentially expressed varies between cell lines. We sought to
      explore the structural determinants of ALDH1A isoform selectivity in a series of
      small-molecule inhibitors in support of research into the role of ALDH1A in
      cancer stem cells. An SAR campaign guided by a cocrystal structure of the HTS hit
      CM39 (7) with ALDH1A1 afforded first-in-class inhibitors of the ALDH1A subfamily
      with excellent selectivity over the homologous ALDH2 isoform. We also discovered
      the first reported modestly selective single isoform 1A2 and 1A3 inhibitors. Two
      compounds, 13g and 13h, depleted the CD133+ putative cancer stem cell pool,
      synergized with cisplatin, and achieved efficacious concentrations in vivo
      following IP administration. Compound 13h additionally synergized with cisplatin
      in a patient-derived ovarian cancer spheroid model.

PMID- 30221941
TI  - Hypervalent Iodine Compounds with Tetrazole Ligands.
AB  - Hypervalent iodine compounds with two I-N bonds, containing 5-substituted
      tetrazoles as the ligands PhI(N4CR)2 (R = CH3, C6H5, and 4-CH3C6H4), were
      synthesized from PhI(O2CCF3)2 or PhICl2 and the corresponding tetrazole potassium
      salts. Alternatively, PhIO was reacted with the free tetrazoles, and the
      reactions afforded either PhI(N4CR)2 or, in most cases, MU-oxo- or oligomeric
      compounds with several I and O atoms in the backbone and two terminal tetrazole
      groups. The isolated compounds were reasonably stable in the solid state as well
      as in solution at room temperature but explosive at elevated temperatures (135
      180  degrees C depending on the structure). The crystal structure of one
      representative compound (an oligomer with three I atoms in the backbone and 5
      phenyltetrazole end groups) was solved and refined from synchrotron powder X-ray
      diffraction. The novel compounds were characterized by cyclic voltammetry and
      were found to be strong oxidants. In addition, they proved to be useful reagents
      for the iodotetrazolylation of unsaturated compounds such as styrene and
      cyclohexene and for the transfer of tetrazole groups to N, N-dimethylaniline.

PMID- 30221942
TI  - Ribosomal Incorporation of Consecutive beta-Amino Acids.
AB  - Due to their unique characteristics, which are not shared by canonical alpha
      peptides, peptides that contain stretches of consecutive beta-amino acids are
      attractive scaffolds for novel peptide drugs and nanomaterials. Although
      ribosomal incorporation of single or nonconsecutive beta-amino acids into
      peptides has previously been reported, the incorporation of consecutive beta
      amino acids has not yet been accomplished. This is primarily due to their
      incompatibility with the ribosomal translation system. Here, we took advantage of
      engineered beta-aminoacyl-tRNAs bearing optimized T-stem and D-arm motifs for
      enhancing binding affinity to EF-Tu and EF-P, respectively. Combined with a
      reconstituted E. coli translation system and optimized translation factor
      concentrations, up to seven consecutive beta-amino acids could be incorporated
      into a model peptide. Furthermore, the synthesis of macrocyclic beta-peptides
      closed by a thioether bond between two d-alpha-amino acids is also demonstrated.
      This represents the first example of the ribosomal synthesis of peptides
      containing stretches of consecutive beta-amino acids.

PMID- 30221943
TI  - Enhanced Oxygen Solubility in Metastable Water under Tension.
AB  - Despite its relevance in numerous natural and industrial processes, the
      solubility of molecular oxygen has never been directly measured in capillary
      condensed liquid water. In this article, we measure oxygen solubility in liquid
      water trapped within nanoporous samples, in metastable equilibrium with a
      subsaturated vapor. We show that solubility increases two fold at moderate
      subsaturations (relative humidity ~0.55). This evolution with relative humidity
      is in good agreement with a simple thermodynamic prediction using properties of
      bulk water, previously verified experimentally at positive pressure. Our
      measurement thus verifies the validity of this macroscopic thermodynamic theory
      to strong confinement and large negative pressures, where significant
      nonidealities are expected. This effect has strong implications for important
      oxygen-dependent chemistries in natural and technological contexts.

PMID- 30221944
TI  - Remote Control of Axial Chirality: Synthesis of Spirooxindole-Urazoles via
      Desymmetrization of ATAD.
AB  - For the first time, a desymmetrization strategy empowered the assembly of a class
      of optically pure spirooxindole-urazoles possessing an N-Ar stereogenic axis via
      remote control of axial chirality in an asymmetric three-component reaction. This
      transformation was realized by a tandem bisthiourea-catalyzed asymmetric Diels
      Alder reaction and substrate-controlled asymmetric ene reaction. The driving
      force derived from aromatization and the high reactivity of 4-aryl-1,2,4-triazole
      3,5-dione enophiles mediated the occurrence of the successive ene reaction under
      mild conditions.

PMID- 30221945
TI  - Combining High-Resolution and Exact Calibration To Boost Statistical Power: A
      Well-Calibrated Score Function for High-Resolution MS2 Data.
AB  - To achieve accurate assignment of peptide sequences to observed fragmentation
      spectra, a shotgun proteomics database search tool must make good use of the very
      high-resolution information produced by state-of-the-art mass spectrometers.
      However, making use of this information while also ensuring that the search
      engine's scores are well calibrated, that is, that the score assigned to one
      spectrum can be meaningfully compared to the score assigned to a different
      spectrum, has proven to be challenging. Here we describe a database search score
      function, the "residue evidence" (res-ev) score, that achieves both of these
      goals simultaneously. We also demonstrate how to combine calibrated res-ev scores
      with calibrated XCorr scores to produce a "combined p value" score function. We
      provide a benchmark consisting of four mass spectrometry data sets, which we use
      to compare the combined p value to the score functions used by several existing
      search engines. Our results suggest that the combined p value achieves state-of
      the-art performance, generally outperforming MS Amanda and Morpheus and
      performing comparably to MS-GF+. The res-ev and combined p-value score functions
      are freely available as part of the Tide search engine in the Crux mass
      spectrometry toolkit ( http://crux.ms ).

PMID- 30221947
TI  - Obtaining consensus in psychotherapy: What holds us back?
AB  - Although the field of psychotherapy has been in existence for well over a
      century, it nonetheless continues to be preparadigmatic, lacking a consensus or
      scientific core. Instead, it is characterized by a large and increasing number of
      different schools of thought. In addition to the varying ways in which
      psychotherapy has been conceptualized, there also exists a long-standing gap
      between psychotherapy research and how it is conducted in actual clinical
      practice. Finally, there also exists a tendency to place great emphasis on what
      is new, often rediscovering or reinventing past contributions. This article
      describes each of these impediments to obtaining consensus and offers some
      suggestions for what might be done to address them. (PsycINFO Database Record

PMID- 30221946
TI  - Integral Equation Prediction of the Structure of Alternating Copolymer
      Nanocomposites near a Substrate.
AB  - The packing structure and phase behavior of polymer-nanoparticle mixtures under
      confinement play an important role in developing strategies for rational design
      of nanomaterials. However, understanding the microscopic dispersion and
      aggregation mechanism of polymer nanocomposites is a great challenge through
      experimental techniques. In this work, the microscopic structure of alternating
      copolymer nanocomposites (ACNs) near a substrate is investigated systematically
      through extension of the inhomogeneous polymer reference interaction site model
      (PRISM) theory. In order to characterize the flexibility and internal chain
      stiffness of copolymers, a semiflexible chain model is introduced to describe the
      intramolecular correlations between different monomers. Based on the bridge
      functionals derived from the fluids density functional theory, the modified
      hypernetted chain closure is integrated with the PRISM equation to form a full
      theoretical framework to capture the density distributions of ACNs. The influence
      of the particle volume fraction, nanoparticle diameter, and adsorption strengths
      between different interaction sites on the packing structure of ACNs under
      confinement is analyzed and discussed in detail. With the increase of the
      particle volume fraction, the size asymmetry between nanoparticles and copolymer
      monomers can greatly influence the density profiles of ACNs near a substrate.
      Increasing the nanoparticle diameter, the density distribution of nanoparticles
      experiences a process from absorbing onto the solid surface to segregating from
      the wall to larger distances. With increasing the adsorption strength between
      copolymers and nanoparticles, the density distribution of nanoparticles
      decreases, which is similar to the case of nanoparticles containing attractive
      interactions. All these characteristics of ACNs show that the current
      inhomogeneous PRISM theory can give a detailed description of the packing
      behavior of different segments. Predictive approaches could be desired and
      developed for design control of alternating copolymer nanocomposites under
      confinement.

PMID- 30221948
TI  - Psychopathy, self-identified race/ethnicity, and nonviolent recidivism: A
      longitudinal study.
AB  - Psychopathy has long been noted to play an important role in the prediction of
      criminal behavior and offending. Although many studies have demonstrated that
      psychopathic traits are predictive of violent recidivism among offenders,
      relatively few studies have examined the predictive validity of psychopathic
      traits for nonviolent recidivism and very few have examined this issue in a
      sample of offenders in the United States. To address this issue, we examined the
      predictive validity of psychopathy for both nonviolent and general recidivism
      using the Psychopathy Checklist-Revised (PCL-R) in a sample of 422 county jail
      inmates. We also examined whether ratings on Factors 1 and 2 differentially
      predicted nonviolent and general recidivism and whether predictive validity
      varied among European American, African American, and Latino American male
      offenders. Psychopathic traits were modestly predictive of nonviolent and general
      (total) recidivism. Factor 2 ratings were not more predictive of nonviolent
      recidivism than Factor 1 ratings in this sample, but the two factor scores also
      predicted nonviolent recidivism interactively. Psychopathic traits were also
      predictive of both outcomes in subsamples of European American and African
      American offenders, but not among Latino American offenders. Findings are
      consistent in magnitude and pattern with prior studies addressing the prediction
      of violence, and they show that the relationship between psychopathy and criminal
      conduct generalizes to the prediction of nonviolent crime in a United States
      offender sample. Results suggest potential differences between the predictive
      validity of psychopathy among Latino American offenders and other racial/ethnic
      groups, which suggest the need for additional research. (PsycINFO Database Record
      (c) 2018 APA, all rights reserved).

PMID- 30221949
TI  - Focusing on the future from afar: Self-distancing from future stressors
      facilitates adaptive coping.
AB  - Prior research indicates that visual self-distancing enhances adaptive self
      reflection about negative past events (Kross & Ayduk, 2011). However, whether
      this process is similarly useful when people reflect on anxiety-provoking future
      negative experiences, and if so, whether a similar set of mechanisms underlie its
      benefits in this context, is unknown. Here we addressed these questions using a
      combination of experimental and individual difference methods with adults and
      adolescents (total N = 2,344). In Studies 1 and 2, spontaneous self-distancing
      predicted less anxious emotional reactivity among adults and adolescents. This
      effect was mediated by differences in how vividly participants imagined a future
      anxiety-provoking event. Study 3 provided causal evidence in an adult sample:
      Adopting a self-distanced (vs. self-immersed) perspective when reflecting on a
      future stressor led to lower levels of anxiety as well as lower imagery
      vividness. Consistent with Studies 1 and 2, reductions in imagery vividness
      mediated the emotion regulatory benefits of self-distancing. A meta-analysis of
      all three studies further confirmed these findings across samples. Thus, the
      current studies extend previous research on the benefits of self-distancing to
      future stressors. In addition, they highlight a novel mechanism for this
      relation: imagery vividness. (PsycINFO Database Record

PMID- 30221950
TI  - A Division 18 conversation with the new APA Chief Executive Officer (CEO): Arthur
      C. Evans, PhD.
AB  - The new Chief Executive Officer of the American Psychological Association (APA)
      Arthur C. Evans, Jr., Ph.D., has a long-standing career in public service and an
      ongoing commitment to public service psychology. Leadership of APA Division 18
      (Psychologists in Public Service) recently interviewed Dr. Evans about his
      position at APA and his vision for public service psychology and its role in the
      U.S. health care system. Issues for discussion were selected by the Division's
      sections on community and state hospitals; criminal justice; police and public
      safety; psychologists in Indian country; serious mental illness/severe emotional
      disturbance; students; and veterans affairs. (PsycINFO Database Record

PMID- 30221952
TI  - Improving the measurement of group-level constructs by optimizing between-group
      differentiation.
AB  - The ability to detect differences between groups partially impacts how useful a
      group-level variable will be for subsequent analyses. Direct consensus and
      referent-shift consensus group-level constructs are often measured by aggregating
      group member responses to multi-item scales. We show that current measurement
      validation practice for these group-level constructs may not be optimized with
      respect to differentiating groups. More specifically, a 10-year review of
      multilevel articles in top journals reveals that multilevel measurement
      validation primarily relies on procedures designed for individual-level
      constructs. These procedures likely miss important information about how well
      each specific scale item differentiates between groups. We propose that group
      level measurement validation be augmented with information about each scale
      item's ability to differentiate groups. Using previously published datasets, we
      demonstrate how ICC(1) estimates for each item of a scale provide unique
      information and can produce group-level scales with higher ICC(1) values that
      enhance predictive validity. We recommend that researchers supplement
      conventional measurement validation information with information about item-level
      ICC(1) values when developing or modifying scales to assess group-level
      constructs. (PsycINFO Database Record

PMID- 30221951
TI  - Mean level of positive affect moderates associations between volatility in
      positive affect, mental health, and alcohol consumption among mothers.
AB  - Affective volatility (i.e., variability) is typically conceptualized as a marker
      of poor mental and behavioral health. The current research challenges this
      notion. Among individuals who typically experience low positive affect (PA),
      vacillation between bouts of joy and marked anhedonia may be associated with
      better behavioral health relative to a restricted range of PA experience. We
      therefore tested the hypothesis that mean levels of PA captured via an 8-day
      intensive repeated Ecological Momentary Assessment (EMA) would moderate the
      association of EMA-measured PA variability with behavioral health measured at
      intake among working mothers (N = 202) with young children-a population at risk
      for experiencing repeated stress- and reward-induced PA changes. Mixed-effects
      location scale modeling parsed variance in PA mean and variability, which were
      used in subject-level regression models of associations with depressive symptoms,
      anxiety, and alcohol use. PA mean moderated the associations of PA variability
      with depressive symptoms (Interaction: beta = .20, p = .02) and alcohol
      consumption frequency (Interaction: beta = .22, p = .02). PA variability and
      depressive symptom and alcohol consumption levels were positively associated at
      higher PA mean levels, whereas PA variability was inversely associated with
      depressive symptom and alcohol consumption at low mean PA. PA Mean * Variability
      Interactions were not significant for anxiety and binge drinking. We conclude
      that (a) intensive longitudinal modeling of Affect Mean * Variability Interaction
      effects may provide incremental information in psychopathology research; (b) PA
      volatility does not unilaterally indicate poor behavioral health; and (c) a
      nuanced perspective on the role of PA volatility may benefit clinical services
      for working mothers. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30221953
TI  - Leaders matter morally: The role of ethical leadership in shaping employee moral
      cognition and misconduct.
AB  - There has long been interest in how leaders influence the unethical behavior of
      those who they lead. However, research in this area has tended to focus on
      leaders' direct influence over subordinate behavior, such as through role
      modeling or eliciting positive social exchange. We extend this research by
      examining how ethical leaders affect how employees construe morally problematic
      decisions, ultimately influencing their behavior. Across four studies, diverse in
      methods (lab and field) and national context (the United States and China), we
      find that ethical leadership decreases employees' propensity to morally
      disengage, with ultimate effects on employees' unethical decisions and deviant
      behavior. Further, employee moral identity moderates this mediated effect.
      However, the form of this moderation is not consistent. In Studies 2 and 4, we
      find that ethical leaders have the largest positive influence over individuals
      with a weak moral identity (providing a "saving grace"), whereas in Study 3, we
      find that ethical leaders have the largest positive influence over individuals
      with a strong moral identity (catalyzing a "virtuous synergy"). We use these
      findings to speculate about when ethical leaders might function as a "saving
      grace" versus a "virtuous synergy." Together, our results suggest that employee
      misconduct stems from a complex interaction between employees, their leaders, and
      the context in which this relationship takes place, specifically via leaders'
      influence over employees' moral cognition. (PsycINFO Database Record

PMID- 30221954
TI  - Boxed in by your inbox: Implications of daily e-mail demands for managers'
      leadership behaviors.
AB  - Over the past 30 years, the nature of communication at work has changed. Leaders
      in particular rely increasingly on e-mail to communicate with their superiors and
      subordinates. However, researchers and practitioners alike suggest that people
      frequently report feeling overloaded by the e-mail demands they experience at
      work. In the current study, we develop a self-regulatory framework that
      articulates how leaders' day-to-day e-mail demands relate to a perceived lack of
      goal progress, which has a negative impact on their subsequent enactment of
      routine (i.e., initiating structure) and exemplary (i.e., transformational)
      leadership behaviors. We further theorize how two cross-level moderators
      centrality of e-mail to one's job and trait self-control-impact these relations.
      In an experience sampling study of 48 managers across 10 consecutive workdays,
      our results illustrate that e-mail demands are associated with a lack of
      perceived goal progress, to which leaders respond by reducing their initiating
      structure and transformational behaviors. The relation of e-mail demands with
      leader goal progress was strongest when e-mail was perceived as less central to
      performing one's job, and the relations of low goal progress with leadership
      behaviors were strongest for leaders low in trait self-control. (PsycINFO
      Database Record

PMID- 30221955
TI  - The kinematics, not the orientation, of an action influences language processing.
AB  - Consistent with the embodied view of cognition, several studies have shown a link
      between action and the processing of action verbs. However, it is largely unknown
      how action properties can influence semantic activation during word processing.
      On the basis of the observation of point-light display (PLDs), the present study
      addressed this issue. Through four experiments, we assessed whether kinematics
      and orientation, which are two crucial characteristics of human action, can
      influence the link between action and language. Participants performed a semantic
      decision task involving action and nonaction verbs after seeing a PLD
      representing either a biological or a nonbiological human movement, the
      kinematics (Experiments 1 and 2) or orientation (Experiment 3) of which was
      modified. Experiment 1 showed that important modifications to the kinematics of
      actions have a direct influence on the link between action and language.
      Experiment 2 confirmed this effect and showed that the effect is somatotopic
      because only modifications to the relevant part of actions affected the link
      between action and language. In contrast, Experiment 3 showed that modifying the
      orientation did not disturb the influence of an action on language probably due
      to the use of a mental rotation strategy. Experiment 4 confirmed this view by
      demonstrating the use of mental rotation when participants have to recognize
      rotated point-light actions. These outcomes shed light on how action properties
      can influence action verbs processing, a crucial step to better understanding the
      link between action and language. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30221956
TI  - How prior information and police experience impact decisions to shoot.
AB  - Social psychologists have relied on computerized shooting tasks to test whether
      race influences decisions to shoot. These studies reveal that under some
      conditions untrained individuals shoot unarmed Black men more than unarmed White
      men. We modeled the decision to shoot as a sequential sampling process in which
      people start out with prior biases and accumulate evidence over time until a
      threshold is reached, prompting a decision. We used this approach to test how
      prior information (a proxy for police dispatch information) and police experience
      influence racial bias in shooting decisions. When no prior information was given,
      target race biased the rate at which untrained civilians accumulated evidence,
      leading to a greater rate of shooting Black targets. For sworn police officers,
      the race of the target impacted prior bias, but not evidence accumulation.
      Moreover, officers showed no race bias in the observed decision to shoot. For
      both untrained civilians and sworn police officers, prior information about a
      target's race was sufficient to eliminate racial bias in shooting decisions both
      at the process and behavioral level. These studies reveal that factors present in
      real-world shooting decisions (dispatch information and police experience) can
      moderate the role that race plays both in the underlying cognitive processes and
      ultimately on the observed decision. We discuss the benefits of using a dynamic
      cognitive model to understand the decision to shoot and the implications of these
      results for laboratory analogues of real-world decisions. (PsycINFO Database
      Record

PMID- 30221957
TI  - Eyes on the prize: The preference to invest resources in goals over means.
AB  - Goal systems are hierarchical, often requiring people to invest resources
      vertically-both in lower-order means and higher-order goals. For example, a
      college student who wants to take a particular class (a goal) might first have to
      take a prerequisite (the means). We investigated how the hierarchical
      configuration of goals and means affects preferences for vertical resource
      allocation. Specifically, we found that within goal-means dyads, people preferred
      to shift resources toward goals (i.e., invest less in means and more in goals)
      and further invested more resources in items framed as goals (versus means;
      Studies 1-2). The preference to shift resources toward goals was moderated by the
      presence of a goal-means hierarchy within the dyad (Study 3) and mediated by the
      perception that investing resources in the goal was a more direct investment in
      goal attainment (Study 4). Moreover, people chose to reduce costs associated with
      means (versus goals; Study 5) and were happier when costs associated with means
      (versus goals) were eliminated (Study 6). These studies demonstrate that the
      aversion to investing resources in means can result in non-normative decision
      making in the course of goal pursuit. (PsycINFO Database Record

PMID- 30221958
TI  - Naysaying and negativity promote initial power establishment and leadership
      endorsement.
AB  - Conventional wisdom holds that leaders should behave in a supportive and positive
      manner. Yet the past decade has also seen a rise in naysayers' ascent to power.
      This research investigates the intriguing possibility that although we may want
      our leaders to be cheerleaders, we instead empower naysayers. Integrating
      theoretical perspectives from psychology, leadership, and organizational theory,
      I present the Naysaying-Agency-Power-Leadership Efficacy (NAPLE) model, which
      captures the causal link between naysaying and power, and examine leadership
      efficacy as a downstream implication. Eleven studies provide empirical support
      for the model. Ten experimental studies demonstrate that naysaying and power are
      causally linked through the perception of agency. An additional study analyzed
      518 eligible voters' assessments of actual statements from U.S. presidential
      debates between 1980 and 2008. Results reveal that voters perceived negative and
      critical presidential candidates as more powerful and, in turn, were more willing
      to vote for them; this finding was robust to controlling for age, gender,
      ethnicity, political orientation, and voting history. By systematically
      establishing that naysaying induces power at the onset, and why, these findings
      illuminate an unanticipated, yet formidable, determinant of power. (PsycINFO
      Database Record

PMID- 30221959
TI  - "Interpersonal emotion regulation: Implications for affiliation, perceived
      support, relationships, and well-being": Correction to Williams et al. (2018).
AB  - Reports an error in "Interpersonal emotion regulation: Implications for
      affiliation, perceived support, relationships, and well-being" by W. Craig
      Williams, Sylvia A. Morelli, Desmond C. Ong and Jamil Zaki (Journal of
      Personality and Social Psychology, 2018[Aug], Vol 115[2], 224-254). In the
      article, there were several errors in Appendices A and B. The formatting of
      Appendix A rendered it inaccessible to the reader, the volume and page range for
      the Williams et al. citation was not updated to reflect final publication
      information, and two e-mail addresses were not correct. Those e-mail addresses
      should appear as wcwill@alumni.stanford.edu and jzaki@stanford.edu. For Appendix
      B, the John et al. (2008) citation should appear directly below the Prosociality
      heading. The online version of this article has been corrected. (The following
      abstract of the original article appeared in record 2018-20533-001.) People often
      recruit social resources to manage their emotions, a phenomenon known as
      interpersonal emotion regulation (IER). Despite its importance, IER's
      psychological structure remains poorly understood. We propose that two key
      dimensions describe IER: (a) individuals' tendency to pursue IER in response to
      emotional events, and (b) the efficacy with which they perceive IER improves
      their emotional lives. To probe these dimensions, we developed the Interpersonal
      Regulation Questionnaire (IRQ), a valid and reliable measure of individual
      differences in IER. Factor analyses of participants' responses confirmed tendency
      and efficacy as independent dimensions of IER (Study 1; N = 285), and
      demonstrated independence between how individuals engage with IER in response to
      negative, versus positive, emotion. In Study 2 (N = 347), we found that
      individuals high in IER tendency and efficacy are more emotionally expressive,
      empathetic, and socially connected. Two subsequent studies highlighted behavioral
      consequences of IER dimensions: people high in IER tendency sought out others
      more often following experimentally induced emotion (Study 3; N = 400), and
      individuals high in IER efficacy benefitted more from social support after real
      world emotional events (Study 4; N = 787). Finally, a field study of social
      networks in freshman dormitories revealed that individuals high in IER tendency
      and efficacy developed more supportive relationships during the first year of
      college (Study 5; N = 193). These data (a) identify distinct dimensions
      underlying IER, (b) demonstrate that these dimensions can be stably measured and
      separated from related constructs, and (c) reveal their implications for
      relationships and well-being. (PsycINFO Database Record

PMID- 30221960
TI  - Does attachment anxiety promote the encoding of false memories? An investigation
      of the processes linking adult attachment to memory errors.
AB  - Previous research has suggested that people's attachment styles influence memory
      processes. Most of this work has focused on the encoding and retrieval of
      information about events that actually took place. The purpose of the present
      research was to determine (a) whether attachment styles also predict memories for
      events that never occurred (false memories); (b) whether experimentally induced
      attachment anxiety leads to the generation of false memories for interpersonal
      experiences; and (c) whether these errors arise during encoding, maintenance, or
      retrieval processes. Our results indicated that attachment anxiety is associated
      with people's propensities to experience false alarms on recognition tasks for
      relational stimuli. Moreover, experimentally altering participants' state levels
      of attachment anxiety led to more numerous false alarms, as compared with an
      unprimed control group. These findings are consistent with the idea that
      attachment-related anxiety might selectively bias and desensitize the encoding of
      interpersonal events, ultimately leading people to remember events that did not
      occur. However, experimentally priming anxiety did not lead to more false alarms
      relative to groups primed with security, raising the possibility that the anxiety
      false memory association could be because of making relational issues salient
      rather than increasing attachment anxiety per se. (PsycINFO Database Record

PMID- 30221961
TI  - Early psychosocial deprivation and adolescent risk-taking: The role of motivation
      and executive control.
AB  - Risk-taking in adolescence has been often associated with early life adversities.
      However, the impact of such macrolevel factors on risk behavior has been rarely
      studied in humans. To address these gaps we recruited a sample of young
      adolescents who were part of a randomized control trial of foster care. Children
      institutionalized at or soon after birth were randomly assigned either to be
      removed from institutions and placed into a family or foster care intervention or
      to remain in institutions receiving care as usual. These children were
      subsequently followed up through 12 years of age and compared with a sample of
      children who had never been institutionalized. Using this sample, we examined the
      impact of early childhood deprivation on risk-taking behavior and explored the
      role of motivation (i.e., sensation seeking) and executive control (i.e.,
      planning). Early psychosocial deprivation decreased engagement in risk-taking
      among young adolescents by reducing sensation seeking, a motivation often
      associated with risk-taking in adolescence. The impact of early psychosocial
      deprivation on sensation seeking and consequently on engagement in risk-taking
      was further reduced by its deleterious effects on executive control. These
      findings challenge the traditional view according to which risk behavior is a
      maladaptive response to adversities and suggest that it may represent
      adolescents' attempts to fulfill important motivations. (PsycINFO Database Record

PMID- 30221962
TI  - Acute stress throughout the memory cycle: Diverging effects on associative and
      item memory.
AB  - Acute stress can modulate memory for individual parts of an event (items), but
      whether it similarly influences memory for associations between items remains
      unclear. We used a within-subjects design to explore the influence of acute
      stress on item and associative memory in humans. Participants associated negative
      words with neutral objects, rated their subjective arousal for each pair, and
      completed delayed item and paired associative recognition tasks. We found
      strikingly different patterns of acute stress effects on item and associative
      memory: for high-arousal pairs, preencoding stress enhanced associative memory,
      whereas postencoding stress enhanced item memory. Preretrieval stress
      consistently impaired both forms of memory. We found that the influence of stress
      induced cortisol also varied, with a linear relationship between cortisol and
      item memory but a quadratic relationship between cortisol and associative memory.
      These findings reveal key differences in how stress, throughout the memory cycle,
      shapes our memories for items and associations. (PsycINFO Database Record

PMID- 30221963
TI  - Community appeal: Explanation without information.
AB  - Formal or categorical explanation involves the use of a label to explain a
      property of an object or group of objects. In four experiments, we provide
      evidence that label entrenchment, the degree to which a label is accepted and
      used by members of the community, influences the judged quality of a categorical
      explanation whether or not the explanation offers substantive information about
      the explanandum. Experiment 1 shows that explanations using unentrenched labels
      are seen as less comprehensive and less natural, independent of the causal
      information they provide. Experiment 2 shows that these intuitions persist when
      the community has no additional, relevant featural information, so the label
      amounts to a mere name for the explanandum. Experiment 3 finds a similar effect
      when the unentrenched label is not widely used, but is defined by a group of
      experts and the recipient of the explanation is herself an expert familiar with
      the topic. The effect also obtains for categories that lack a coherent causal
      structure. Experiment 4 further demonstrates the domain generality of the
      entrenchment effect and provides evidence against several interpretations of the
      results. A majority of participants in Experiments 3 and 4 could not report the
      impact of entrenchment on their judgments. We argue that this reliance on
      community cues arose because the community often has useful information to
      provide about categories. The common use of labels as conduits for this communal
      knowledge results in reliance on community cues even when they are uninformative.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30221964
TI  - The contribution of employment duration to 18-month neurocognitive outcomes in
      first-episode psychosis.
AB  - OBJECTIVE: Increased employment duration has been associated with change in
      performance on specific neurocognitive domains in populations with schizophrenia,
      but not in first-episode psychosis. The aim of this exploratory study was to
      examine whether employment duration over 18 months is associated with
      neurocognitive outcomes over 18 months among individuals with first-episode
      psychosis. METHOD: Eighty-eight young people with first-episode psychosis
      completed a neurocognitive battery at baseline and 18 months. Setwise
      (hierarchical) multivariate linear regressions were used to examine predictors of
      change in neurocognitive performance over 18 months. Total hours employed over 18
      months were entered after accounting for age, gender, premorbid IQ, and negative
      symptom change scores. RESULTS: Total hours employed was significantly associated
      with change in Symbol Digit Modalities Test raw score (p = .020), Letter-Number
      Sequencing scaled score (p = .016), Digit Span total scaled score (p = .047) and
      Rey Complex Figure Test delayed recall raw score (p = .016) over 18 months, after
      controlling demographic characteristics, premorbid IQ, and changes in negative
      psychotic symptoms. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Total hours worked
      over 18 months was associated with small improvements on one test of processing
      speed and one test of working memory. However, total hours worked over 18 months
      was also associated with decline on one test of attention and working memory and
      visual organization and memory. The findings implicate that work alone may not be
      entirely effective in changing neurocognitive functioning for young people with
      first-episode psychosis. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30221965
TI  - The association between time incarcerated and the search for employment in a
      veteran sample with substance use disorders.
AB  - OBJECTIVE: Incarceration and substance use disorders/mental illness can have a
      significant negative impact on finding employment. However, it is unclear in what
      phase of the search for employment, that is, applying for jobs, obtaining
      interviews, being offered employment, does time incarcerated have the most
      effect. This study will determine how time incarcerated in the past 10 years is
      associated with negative job search process outcomes. METHOD: This study
      evaluates 84 (81 men and 3 women) veterans with substance use disorders and
      histories of felony convictions. Four path analyses were conducted to evaluate
      models that incorporated time incarcerated at the different phases. RESULTS: The
      superior model incorporated time incarcerated negatively affecting the number of
      interviews obtained. Models that assessed the association between time
      incarcerated with applications submitted and likelihood of being offered
      employment did not demonstrate adequate goodness-of-fit. CONCLUSION AND
      IMPLICATIONS FOR PRACTICE: Overall, the findings demonstrate the ex-offenders
      enrolled exhibited similar effort in searching for employment across time
      incarcerated. Also, employers are equally likely to hire those with felony
      histories, regardless of the time incarcerated, once the applicant has been met
      and interviewed. The results highlight the need for services focusing on breaking
      down stigma and reducing barriers that screen out ex-offenders from being
      interviewed by employers. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30221966
TI  - Arts-based psychiatric rehabilitation programs in the community: Perceptions of
      healthcare professionals.
AB  - OBJECTIVE: Despite the increase in arts-based programs in community
      rehabilitation services in many countries, little is known about how these
      programs are perceived by health professionals who can refer individuals with
      mental health conditions to community-based psychiatric rehabilitation services.
      This study examined how senior professionals with key positions in the public
      health system perceive the integration of the arts in community-based psychiatric
      rehabilitation services in Israel. METHOD: Semistructured interviews were
      conducted with 10 professionals. RESULTS: The thematic analysis revealed 2 main
      themes. The first reflected "the perceived position of arts-based programs among
      other rehabilitation services," and had 2 subthemes: arts as a legitimate
      supplemental service, and arts as a motivating rehabilitation. The second theme
      reflected "the unique contribution of the arts to recovery processes," and had 3
      subthemes: art-making facilitates self-expression and communication and bypasses
      resistance, art-making facilitates socialization, and art-making shapes and
      enhances personal identity. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Because
      most of the professionals were exposed to the creative arts in their workplace,
      they valued their contribution to the rehabilitation process. Thus, direct
      contact can provide more information, more accurate perceptions, and a better
      understanding of the benefits of arts-based services, which may in turn encourage
      service managers and policymakers to include these services. (PsycINFO Database
      Record

PMID- 30221967
TI  - The relationship between social support and personal recovery in bipolar
      disorder.
AB  - OBJECTIVE: Mood symptoms may impact on personal recovery and psychosocial
      functioning in bipolar disorder (BD). This study aimed to explore whether recent
      mood symptoms were associated with recovery and social support from friends,
      family, and partners. METHOD: A cross-sectional survey was conducted with 312
      participants who self-reported a confirmed diagnosis of BD and were recruited
      through social media. RESULTS: A series of one-way analyses of variance (ANOVA)
      were conducted. Those who reported depression (52%) or hypo/mania (47%) reported
      lower recovery scores. Those who reported seeing family and >1 friend reported
      higher recovery scores along with those who were employed, did not receive
      benefits, and had higher education. Recent hypo/mania symptoms were associated
      with less family contact. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Friends and
      family may be conducive to recovery, however recent symptoms may have an impact.
      More research is required to understand how hypo/mania symptoms may influence
      accessing family support. (PsycINFO Database Record

PMID- 30221968
TI  - Optimism and the conserved transcriptional response to adversity.
AB  - Dispositional optimism, a personality trait predisposing individuals to positive
      expectations, has been suggested to promote better health. However, little is
      known about the biological mechanism of the salubrious health effects of
      optimism. We hypothesized that by diminishing a sense of threat to the self,
      optimism will be associated with a healthier profile of gene expression in immune
      cells. Specifically, the "conserved transcriptional response to adversity" (CTRA)
      is activated by fight-or-flight stress responses and results in increased
      transcription of genes involved in inflammation and decreased transcription of
      genes involved in antiviral defense. In a sample of 114 male Japanese workers, we
      found that optimism was inversely linked to CTRA after controlling for
      demographic variables, health-risk factors, and indices of well-being. These
      results are consistent with the hypothesis that reduced activity of threat
      related gene expression programs may contribute to the health effects associated
      with optimism. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30221969
TI  - Social nudging: The effect of social feedback interventions on vaccine uptake.
AB  - OBJECTIVE: Most vaccines provide indirect community protection by preventing the
      transmission of the disease. Paradoxically, this effect can also motivate
      omission of vaccination because increasing vaccination rates reduce the risk of
      infection and, therefore, the individual benefit of vaccination. Consequently,
      vaccination becomes a social dilemma where individuals' interests conflict with
      group interests. The current study investigated two social nudge interventions
      aiming to increasing individuals' motivation to act in the group's interest.
      Rewarding the attainment of the goal (disease elimination) is hypothesized to
      increase goal-directed behavior (vaccination). Further, it is assumed that
      comparisons with another group increase cooperative vaccination within one's own
      group. METHOD: In a laboratory experiment, the interactive vaccination (I-Vax)
      game was used to model the direct and indirect effects of vaccinations. The game
      was played by 288 participants over 20 rounds. The experimental setup varied the
      feedback information after each round to implement a 2 (rewarding goal
      attainment: present vs. absent) * 2 (intergroup comparison: present vs. absent)
      between-subjects design. RESULTS: Analyses revealed the expected positive effect
      of rewarding goal-attainment, which was particularly strong at the beginning and
      weakened over the course of repeated decisions. The effect of intergroup
      comparisons was also positive but did not reach conventional criteria of
      statistical significance. CONCLUSIONS: The current experiment shows that
      communicating and rewarding "small wins" may increase individuals' willingness to
      act in the group's interest. Intergroup processes deserve further attention and
      investigation as potential strategies for improving vaccine communication and
      advocacy. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30221970
TI  - Understanding and predicting a complex behavior using n-of-1 methods:
      Photoprotection in xeroderma pigmentosum.
AB  - OBJECTIVE: Xeroderma pigmentosum (XP) is a very rare inherited disease; the most
      important aspect of clinical management is rigorous photoprotection from
      ultraviolet radiation. The aims of this novel study were to (a) understand and
      categorize the behavioral complexity and within-participant variability in
      photoprotection of the face in XP; (b) determine the predictors of
      photoprotection; and (c) identify individual needs for personalized
      interventions. METHOD: A total of 20 adults with XP completed an ecological
      momentary assessment (EMA) study over 50 days. Measures included an ultraviolet
      radiation diary of photoprotective behaviors used at each outdoor occasion (e.g.,
      hat, face visor, sunscreen), and a mobile phone survey assessing self-reported
      protection (0-100), satisfaction with protection achieved, and predictive
      variables (e.g., motivation, effort, mood). Descriptive statistics for
      photoprotective behavior were computed, per person. When possible, individual
      dynamic logistic regression models were used to investigate the predictors of
      photoprotection, and correspondence between self-reported protection and
      behavior. RESULTS: Photoprotection (clothing and sunscreen) was suboptimal for
      most participants, and discrepancies between self-reported protection and
      behavior were identified. Modeling of photoprotection was conducted for six
      participants who went outside sufficient times and used varied protection.
      Different predictors were identified across participants. Weekend versus weekday,
      physical symptoms, stress, and feeling self-conscious were most frequently
      associated with protection. CONCLUSION: The findings support the need for
      intervention and have implications for the selection of individually tailored
      behavioral outcomes and intervention targets to improve photoprotection. The
      method of profiling multiple preventive behaviors using EMA may be of use in
      other rare conditions involving complex behaviors. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30221971
TI  - Switching from endoscopic submucosal dissection to salvage piecemeal knife
      assisted snare resection to remove a lesion: A preoperative risk score from the
      beginning.
AB  - BACKGROUND AND AIMS: endoscopic submucosal dissection (ESD) in the Western
      setting remains a challenge. Therefore, other simplified techniques such as knife
      assisted snare resection (KAR) have been reported to overcome this issue.
      METHODS: patients who underwent an ESD for the treatment of gastrointestinal
      neoplasms were included in a retrospective cross-sectional observational study.
      Factors associated with the end of ESD as a salvage p-KAR were identified and a
      logistic regression model was developed. RESULTS: a total of 136 lesions in 133
      patients were analyzed. Operator experience of under 50 cases and the combination
      of lesion size > 30 mm and colorectal location were independent predictive
      factors for switching to a salvage p-KAR according to the multivariate logistic
      regression analysis. We developed a risk scoring system based on these four
      variables (experience, size, location and the combination of size and location)
      with a receiver operating characteristic curve of 0.81 (95% CI: 0.74-0.89). The
      diagnostic accuracy of the score for a cut-off point >= 5 had a sensitivity of
      0.79 (95% CI: 0.66-0.93) and a specificity of 0.71 (95% CI: 0.61-0.80).
      CONCLUSION: a simple predictive score system that includes four preoperative
      factors accurately predicts ESD to finish as a p-KAR. A careful selection of
      cases considering these variables could be useful to achieve better outcomes in
      the Western setting.

PMID- 30221972
TI  - Sexual Orientation and Depressive Symptoms Among High School Students in Jiangxi
      Province.
AB  - Research in western countries has shown that adolescents who self-identify as
      lesbian, gay, or bisexual (LGB) are at increased risk for depression, but little
      is known about this relationship among adolescents in China. A school-based cross
      sectional survey was conducted among 1816 high school students in Jiangxi
      province. Logistic regression was used to explore the relationship between sexual
      orientation and depressive symptoms. Approximately 4% of participants self
      identified as LGB, and 14% reported being unsure of their sexual identity. After
      controlling for potential confounding factors, students who self-identified as
      LGB had significantly higher odds of depressive symptoms compared with
      heterosexual students: adjusted odds ratio = 6.16 (2.13-17.83) and adjusted odds
      ratio = 2.29 (1.13-4.63) for males and females, respectively. Culturally
      appropriate programs and policies that support LGB students and address
      discrimination and victimization are needed to improve the mental health of
      Chinese LGB youth.

PMID- 30221973
TI  - Relationship Between Postoperative Neutrophil-Lymphocyte Ratio and 6-Month
      Primary Patency of Percutaneous Transluminal Angioplasty in Femoropopliteal
      disease With Drug-Coated and Uncoated Balloons.
AB  - We investigated the relationship of postoperative neutrophil-lymphocyte ratio
      (NLR) with 6-month primary patency of percutaneous transluminal angioplasty (PTA)
      in femoropopliteal disease using drug-coated balloon (DCB) or uncoated balloon
      (UCB). This retrospective study included 106 patients who received DCB (n = 44)
      or UCB (n = 62). The postoperative NLR was lower in the DCB group than that in
      the UCB group (2.60 vs 3.23; P = .004), and 6-month primary patency rate was
      significantly higher in DCB group than that in the UCB group (77.3% vs 53.2%; P =
      .011). Multivariate logistic analysis showed that the postoperative NLR was an
      independent predictor of 6-month primary patency after PTA in patients with
      femoropopliteal disease (odds ratio: 1.589, 95% confidence interval: 1.078-2.343;
      P = .019). The cutoff value of postoperative NLR was 3.05 for prediction of 6
      month primary patency, with a sensitivity of 64.1% and specificity of 65.7%. The
      6-month primary patency rate in the NLR <=3.05 group was higher than that in the
      NLR >3.05 group (75.9% vs 47.9%; P = .003). In conclusion, DCB may improve early
      primary patency by inhibiting inflammation. A higher postoperative NLR was
      associated with early restenosis.

PMID- 30221974
TI  - Implementation of an Algorithm Utilizing Saline Versus Albumin for the Treatment
      of Intradialytic Hypotension.
AB  - BACKGROUND: Intradialytic hypotension (IDH) is the most commonly reported
      complication of hemodialysis (HD) treatment. At our institution, dialysis
      patients often have both 25% albumin and normal saline ordered as rescue options
      for management of IDH, without specification of which agent to use first.
      OBJECTIVE: The purpose of this study was to determine the effect of an algorithm
      for IDH management. METHODS: A retrospective study was conducted in HD patients
      who experienced IDH. The primary end point was to evaluate albumin use. Secondary
      end points included albumin costs, study fluid use per dialysis session,
      compliance with algorithm, efficacy of hypotension reversal to mean arterial
      pressure (MAP) ?60 mm Hg, percentage of target ultrafiltration achieved, time
      required to restore systolic blood pressure ?90 mm Hg, blood pressure post-study
      fluids, IDH treatment failure rate, and early termination of dialysis as a result
      of persistent IDH. RESULTS: Implementation of the algorithm was observed in 94%
      of patients (n = 90). Total albumin use was significantly reduced from 11 400 to
      4700 mL in the pre- (n = 90) and post-algorithm implementation group (n = 90; P <
      0.001). The associated total cost of albumin was reduced by 59% ($10 534 vs
      $4343; P < 0.001). No statistical differences were observed between the 2 groups
      regarding efficacy of hypotension reversal to MAP ?60 mm Hg, early HD
      termination, or treatment failure rates (all P = 0.99). Conclusion and Relevance:
      Implementation of an evidence-based, standardized algorithm and pharmacy
      education to nursing staff can result in a reduction in albumin use and its
      associated drug costs for IDH management without compromising efficacy of IDH
      reversal.

PMID- 30221975
TI  - Properties of the Continuous Assessment of Interpersonal Dynamics Across Sex,
      Level of Familiarity, and Interpersonal Conflict.
AB  - The Continuous Assessment of Interpersonal Dynamics (CAID) is a method in which
      trained observers continuously code the dominance and warmth of individuals who
      interact with one another in dyads. This method has significant promise for
      assessing dynamic interpersonal processes. The purpose of this study was to
      examine the impact of individual sex, dyadic familiarity, and situational
      conflict on patterns of interpersonal warmth, dominance, and complementarity as
      assessed via CAID. We used six samples with 603 dyads, including two samples of
      unacquainted mixed-sex undergraduates interacting in a collaborative task, two
      samples of couples interacting in both collaborative and conflict tasks, and two
      samples of mothers and children interacting in both collaborative and conflict
      tasks. Complementarity effects were robust across all samples, and individuals
      tended to be relatively warm and dominant. Results from multilevel models
      indicated that women were slightly warmer than men, whereas there were no sex
      differences in dominance. Unfamiliar dyads and dyads interacting in more
      collaborative tasks were relatively warmer, more submissive, and more
      complementary on warmth but less complementary on dominance. These findings speak
      to the utility of the CAID method for assessing interpersonal dynamics and
      provide norms for researchers who use the method for different types of samples
      and applications.

PMID- 30221976
TI  - Exploratory Factor Analysis of Observational Parent-Child Interaction Data.
AB  - The majority of studies using observational coding systems for family interaction
      data derive scales describing family members' behaviors based on
      rational/theoretical approaches. This study explored an empirical approach to
      identifying the component structure of parent-child observational data that
      incorporated the affective context of the interaction. Dyads of 155 typically
      developing 8-year-olds and their mothers completed questionnaires and two
      interaction tasks, one each designed to illicit positive and negative
      interactions. Behaviors were coded based on a modified version of the Family
      Interaction Macro-coding System. Multiple factor analysis identified four
      component solutions for the maternal and child data. For both, two of the
      components included negative behaviors, one positive behavior, and one
      communicative behavior. Evidence for the validity of the maternal and child
      components was demonstrated by associations with child depression and anxiety
      symptoms and behavioral problems. Preliminary evidence supports an empirical
      approach to identify context-specific components in parent-child observational
      data.

PMID- 30221977
TI  - Minimal Clinically Important Differences and Substantial Clinical Benefit in
      Patient-Reported Outcome Measures after Autologous Chondrocyte Implantation.
AB  - Objective We sought to determine the minimal clinically important difference
      (MCID) and substantial clinical benefit (SCB) associated with the Knee Injury and
      Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee
      (IKDC) Subjective Knee Evaluation Form, Lysholm, and Short Form-12 (SF-12) after
      autologous chondrocyte implantation (ACI). Design Ninety-two patients with
      satisfaction surveys at a minimum of 2 years postoperatively and at least 1
      repeated patient-reported outcome measure (PROM) were analysed. The MCID was
      determined using 4 anchor-based methods: average change, mean change, minimally
      detectable change, and the optimal cutoff point for receiver operating
      characteristic (ROC) curves. If an anchor-based method was not applicable,
      standard deviation-based and effect size-based estimates were used. SCB was
      determined using ROC curve analysis. Results The 4 anchor-based methods provided
      a range of MCID values for each PROM (11-18.8 for the KOOS pain, 9.2-17.3 for the
      KOOS activities of daily living, 12.5-18.6 for the KOOS sport/recreation, 12.8
      19.6 for the KOOS quality of life, 10.8-16.4 for the IKDC, and 6.2-8.2 for the SF
      12 physical component summary). Using the 2 distribution-based methods, the
      following MCID value ranges were obtained: KOOS symptom, 3.6 to 8.4; the Lysholm,
      4.2 to 10.5; and the SF-12 mental component summary, 1.9 to 4.6. SCB was 30 for
      the KOOS sport/recreation and 34.4 for the IKDC, which most accurately predict
      substantial improvement. No significant association was noted between SCB
      achievement and the baseline PROMs. Conclusion The MCID and SCB determined in our
      study will allow interpretation of the effects of treatment in clinical practice
      and trials. Given the varied MCID values in this study, standardisation of the
      most appropriate calculation methods is warranted.

PMID- 30221978
TI  - Seventeen-Year Changes in Body Mass Index, Waist Circumference, Elevated Blood
      Pressure, and Diabetes Phenotypes in a Cohort of Filipino Women.
AB  - Obesity, hypertension, and diabetes have risen dramatically in Asia, but few
      cohort studies track age and secular trends in these conditions. We use Cebu (The
      Philippines) Longitudinal Health and Nutrition survey data to document 1998 to
      2015 prevalence and co-occurrence of body mass index (BMI; >25 kg/m2), high waist
      circumference (WC; >80 cm), elevated blood pressure (EBP; systolic ?130 or
      diastolic ?85 mm Hg), and type 2 diabetes among ~2000 women aged 29 to 62 years
      in 1998; and identify their relationship to community, household, and individual
      factors using longitudinal logistic regression. Prevalence (1998-2015) rates were
      35% to 49%, BMI >25 kg/m2; 32% to 58% high WC; 21% to 59% EBP; and 2% to 14%
      diabetes. Only 20% of women had none of these conditions in 2015. Diabetes was
      strongly driven by age and secular trends in high WC related to higher
      socioeconomic status and urbanization. Hypertension increased with age in lower
      socioeconomic status rural and more affluent urban women. Results underscore the
      continuing need for public health measures to prevent obesity and to identify and
      treat hypertension and diabetes.

PMID- 30221979
TI  - Incorporation of Cervista Human Papillomavirus 16/18 Assay Into Algorithms for
      Classifying Human Papillomavirus Status in Formalin-Fixed Paraffin-Embedded Head
      and Neck Squamous Carcinoma Specimens.
AB  - CONTEXT: - Human papillomavirus (HPV) DNA in situ hybridization (ISH) assay and
      p16 immunohistochemistry (IHC) are used to determine high-risk HPV status in
      formalin-fixed, paraffin-embedded (FFPE) tissues in oropharyngeal squamous cell
      carcinoma (SCC). Although high sensitivity and specificity for HPV can be
      obtained by combined p16-IHC and HPV DNA-ISH, the occasional discrepancy between
      these assays has prompted evaluation of Cervista HPV assays in FFPE tissue from
      patients with oropharyngeal SCC. OBJECTIVE: - To compare the efficacy of Cervista
      HPV 16/18 and Cervista HPV HR assay to that of HPV DNA-ISH assay and p16-IHC in
      FFPE tissue in head and neck squamous cell carcinoma of oropharyngeal origin.
      DESIGN: - Archived FFPE tissue from 84 patients with SCC of oropharyngeal origin
      and available HPV DNA-ISH and p16-IHC test results were tested with the Cervista
      HPV 16/18 assay and further verified by polymerase chain reaction (PCR)-based
      HPV16/18 genotyping tests in cases with discrepancy. RESULTS: - Of the 84
      specimens, 75% (63 of 84) were positive and 16% (13 of 84) had discrepant or
      equivocal findings by p16-IHC and HPV DNA-ISH testing. Use of Cervista HPV
      assays, either to clarify discrepant/equivocal findings or as confirmation after
      initial p16-IHC/HPV DNA-ISH tests, identified 81% (68 of 84) of HPV-positive
      cases without equivocal HPV results. Five of 13 cases with discrepancy or
      equivocal HPV DNA-ISH results tested positively for HPV16 or HPV18 by Cervista
      HPV 16/18 assay, which was further confirmed by PCR-based HPV16/18 genotyping.
      CONCLUSIONS: - The Cervista HPV assays are a reasonable alternative to HPV DNA
      ISH in determining HPV status in FFPE tissue specimens from patients with
      oropharyngeal SCC.

PMID- 30221980
TI  - Follicular Lymphoma Diagnostic Caveats and Updates.
AB  - CONTEXT.-: Follicular lymphoma is a common small B-cell lymphoma, likely to be
      encountered by any practicing pathologist, regardless of specialty. Although the
      features of typical follicular lymphoma are well known and in most instances
      easily identifiable, there are lesser-appreciated morphologic appearances that
      can raise alternative diagnostic possibilities. The limited tissue available in
      core needle biopsies can make it additionally challenging to thoroughly evaluate
      those features in the context of architecture. Furthermore, ancillary testing
      including immunohistochemistry and molecular/genetic analysis do not always show
      classic findings and may pose additional challenges to interpretation.
      OBJECTIVES.-: To review the morphologic features of follicular lymphoma with a
      discussion of morphologic variants and mimics; to discuss pitfalls of ancillary
      testing and provide the practicing pathologist with an appropriate context for
      interpretation of immunohistochemical and molecular/genetic studies when
      follicular lymphoma is part of the differential diagnosis; and to propose
      diagnostic strategies when there is limited tissue for evaluation. DATA SOURCES.
      : We used examples of follicular lymphoma from our institution as well as a
      review of the literature, with a focus on the diagnostic aspects that are broadly
      relevant to a general pathology practice. CONCLUSIONS.-: Follicular lymphoma can
      occasionally present with atypical morphologic, immunohistochemical, or
      molecular/genetic features. In particular, those findings can be difficult to
      interpret in the setting of a limited tissue sample. Awareness of those
      possibilities will help guide the pathologist to a more accurate and precise
      diagnosis.

PMID- 30221982
TI  - The Public Health Challenge of Ending Malnutrition: The Relevance of the World
      Health Organization's GINA Database.
AB  - In order to address malnutrition, implementation of nutrition actions is needed.
      While academic institutions will certainly play a part, strong coordination and
      leadership from major United Nations agencies are needed. To this effect, the
      World Health Organization has launched a Global Database on the Implementation of
      Nutrition Action (GINA). It contains information collected from various sources,
      including direct submissions by users. Users can share information on how
      programs are implemented, including country adaptations and lessons learnt. GINA
      allows users to share implementation experience in order to identify overlaps and
      gaps, to foster discussion toward improved planning and to promote good
      practices. The aim of this article is to highlight the relevance of the GINA
      database in meeting the public health challenge of ending malnutrition and,
      therefore, to encourage users from different countries to enter programs and
      policies in the database.

PMID- 30221981
TI  - Removal of the Long Spine Board From Clinical Practice: A Historical Perspective.
AB  - Since the early 1970s, initial management of patients with suspected spinal
      injuries has involved the use of a cervical collar and long spine board for full
      immobilization, which was thought to prevent additional injury to the cervical
      spine. Despite a growing body of literature demonstrating the detrimental effects
      and questionable efficacy of spinal immobilization, the practice continued until
      2013, when the National Association of EMS Physicians issued a position statement
      calling for a reduction in the use of spinal immobilization and a shift to spinal
      motion restriction. This article examines the literature that prompted the change
      in spinal-injury management and the virtual elimination of the long spine board
      as a tool for transport.

PMID- 30221983
TI  - Family-Based Social Health Insurance for Informal Workers in Vietnam: Willingness
      to Pay and Its Determinants.
AB  - The study aimed to assess willingness to pay for family-based social health
      insurance and its determining factors among informal workers in Vietnam. A double
      bounded dichotomous choice approach was used to elicit the willingness to pay of
      391 heads of uninsured households. The study indicates that 48.8% of 391
      uninsured households were willing to pay for family-based health insurance. The
      households were willing to pay about 921.9 thousand Vietnamese dongs per
      household per year (US$42). The factors that significantly affected willingness
      to pay were household income, number of uninsured members in a household, and
      sickness of the household head. The study suggests that a feasible premium for
      family-based health insurance supported by government subsidy, along with
      attention to the quality improvements of health services, could be an effective
      means to increase coverage among the informal sector workers.

PMID- 30221984
TI  - Effects of unilateral nasal obstruction on the characteristics of jaw-closing
      muscles in growing rats.
AB  - OBJECTIVES:: Mouth breathing caused by nasal obstruction (owing to abnormal
      pressure of masticatory muscles) affects craniofacial growth and development. The
      influence of unilateral nasal obstruction on jaw-closing muscles was investigated
      in rats to reveal one of the etiologic mechanisms. MATERIALS AND METHODS:: Forty
      8-day-old male Wistar rats were used in this study. Experimental rats were
      subjected to left-sided nasal obstruction by burning the external nostril tissue
      at the age of 8 days. Pulse oxygen saturation was recorded each week. Morphologic
      changes were evaluated by staining with hematoxylin and eosin (to assess the
      cross-sectional area) and by adenosine triphosphatase activity staining (to
      assess the myosin heavy chain isoform composition). Immunohistochemical and
      reverse transcription quantitative real-time polymerase chain reaction analyses
      of tumor necrosis factor-alpha and glucose transporter 4 were carried out at 5
      and 9 weeks of age. RESULTS:: The cross-sectional area of the jaw-closing muscles
      was lower in the experimental group at 9 weeks of age. The percentage of myosin
      heavy chain-2a in masseter muscles was increased in the experimental group
      compared with the control group. An increase in the tumor necrosis factor-alpha
      messenger RNA and protein levels and a decrease in the glucose transporter 4
      messenger RNA and protein levels at 5 and 9 weeks of age in the jaw-closing
      muscles in the experimental group were noted. CONCLUSIONS:: Unilateral nasal
      obstruction could affect the morphology and contractile characteristics of jaw
      closing muscles during growth in rats.

PMID- 30221985
TI  - Formaldehyde Exposure in Indoor Air From Public Places and Its Associated Health
      Risks in Kunshan City, China.
AB  - This study assessed the noncarcinogenic and carcinogenic health risks associated
      with formaldehyde exposure for employees working in 4 categories of public places
      in Kunshan City in China. A total of 564 different public places, which can be
      divided into 4 categories (hotel and social interaction places, bathing and
      beauty places, cultural and entertainment places, and shopping places), and 2716
      indoor air samples in those places were measured from January 1, 2010, to
      December 31, 2015. The average concentration of formaldehyde was 0.57 mg/m3,
      which is 5.7 times the acceptable concentration level (0.1 mg/m3). The
      noncarcinogenic risk assessment index for the 4 categories of places tested was
      above 1. The carcinogenic risk of formaldehyde for employees of the 4 categories
      of public places was 4.70 * 10-5 to 1.57 * 10-4, which was greater than the
      acceptable carcinogenic risk probability (1 * 10-6) from the US Environmental
      Protection Agency. The highest carcinogenic risk occurred in bathing and beauty
      places, and male employee carcinogenic risk was greater than that of females.
      Occupational formaldehyde exposure has serious noncarcinogenic and carcinogenic
      health risks for employees, and further research is needed to improve indoor air
      quality in the workplace environment.

PMID- 30221986
TI  - Arthroscopic Meniscopexy for the Treatment of Nontraumatic Osteochondritis
      Dissecans in the Knee Joint of Adult Patients.
AB  - Objective The etiology of osteochondritis dissecans (OCD) is still uncertain.
      Recently, it has been hypothesized that instability of the anterior horn of the
      meniscus is an important cause for the development of a nontraumatic OCD in
      adolescents with good results after surgical stabilization. This case series aims
      to evaluate the treatment results after meniscus stabilization in adults with
      nontraumatic OCD. Design Ten patients with magnetic resonance imaging (MRI)
      confirmed OCD of the knee joint, meniscal instability, and closed epiphyseal
      plates were enrolled in this study. The instable meniscus was stabilized by
      direct suturing of the anterior horn of the meniscus. MRI examinations were
      performed preoperative and 6 and 12 months postoperative. The OCD was classified
      arthroscopically according to Guhl and according to Hughes in the MRI. The
      overall knee function was evaluated by the Lysholm score before treatment and 12
      months postoperative. Results Four women and 6 men with a mean age of 20.6 +/-
      1.9 years were included in this study. Preoperatively 60% of the patients showed
      a grade II or III lesion arthroscopically and 70% a grade III or IVa lesion in
      the MRI examination. After arthroscopic meniscus stabilization the Lysholm score
      increased in average from 48.1 +/- 14.12 before treatment to 97.5 +/- 3.1
      postoperative. At final follow-up after 12 months, an improvement of the OCD in
      the MRI could be demonstrated in all patients (100%). In 80% of the patients a
      complete healing of the OCD could be noted. Conclusion The clinical concept of an
      instable anterior horn of the meniscus as a cause for the development of a
      nontraumatic OCD seems to be transferable to adults and arthroscopic
      stabilization can lead to a sufficient healing of this knee pathology.

PMID- 30221987
TI  - C-Terminal Cross-Linked Telopeptides of Type II Collagen as Biomarker for
      Radiological Knee Osteoarthritis: A Meta-Analysis.
AB  - Background C-terminal cross-linked telopeptides of type II collagen (CTX-II) are
      one of the most frequently assessed markers for osteoarthritis (OA) diagnosis.
      The aim of this meta-analysis was to confirm the diagnostic value of urinary CTX
      II in knee OA. Materials and Methods PubMed, ScienceDirect, and EMBASE were
      searched for studies measured urinary CTX-II in patients with knee OA and in
      healthy controls. Urinary CTX-II levels were compared between knee OA patients
      and controls. Differences between groups were expressed as standardized mean
      differences (SMD) when individual outcomes were measured with different scales.
      Otherwise, outcomes were presented as mean differences (MD). Subgroup analyses
      were also conducted to compare efficiency of urinary CTX-II between Kellgren
      Lawrence (KL) classification, genders, ethnicities, and study size. Results
      Thirteen studies involved a total of 2856 participants were included. Pooled SMD
      showed that urinary CTX-II levels were significantly elevated in knee OA group
      compared to controls (SMD 0.82; 95% CI 0.41-1.24; P < 0.0001). For KL 3 to 4
      versus KL 2, higher urinary CTX-II levels were found in severe knee OA patients.
      Subgroup analyses revealed that urinary CTX-II performed better in females as
      compared with males and in European subjects as compared with Asian population.
      Also, study size did not influence the statistic results. Conclusion This is the
      largest scale meta-analysis assessing the diagnostic performance of urinary CTX
      II levels as biomarker for knee OA. According to our findings, urinary CTX-II
      levels have a potential to distinguish knee OA patients from healthy controls
      which can serve as biomarker for knee OA.

PMID- 30221988
TI  - The Use of Microblog "Weibo" by Chinese Patent Medicine Companies in China.
AB  - BACKGROUND: In order to introduce regulatory measures to regulate social media
      use by the Chinese patent medicine (CPM) companies, it needs better understanding
      of CPM companies' promotional activities using social media. Thus, this study
      aimed to analyze the nature of the information conveyed to the public by the CPM
      companies through microblog (Weibo) in China. METHODS: The content of 17 CPM
      Weibo accounts was analyzed. These accounts were established by 13 CPM companies,
      each of which had more than 10,000 followers, over 1000 posts and updated posts
      in 2016. RESULTS: Of the 40,798 original posts identified in the 17 Weibo
      accounts, 98.39% (n = 40,142) were classified into 6 main themes: (1) social
      living (36%); (2) health science (26%); (3) health maintenance (14%); (4) direct
      product promotion (11%); (5) corporate branding (7%); and (6) medical and
      industrial information (6%). Among the posts directly related to product
      promotion, more than half (n = 2550) focused on customer interactions followed by
      product efficacy (n = 945). Among the posts about corporate branding, about half
      of them (n = 1,443) focused on company image. CONCLUSIONS: Weibo is being used by
      CPM companies widely for strategic product promotion. With one of the key
      strategies being overt marketing driven by covert marketing, a large amount of
      health-related information is disseminated through this platform. Regulatory
      policies to ensure the credibility of information disseminated in the social
      media used by the CPM companies for promotion purposes are warranted to help
      protect the public's interests.

PMID- 30221989
TI  - Extracellular Matrix Determines Biomechanical Properties of Chondrospheres during
      Their Maturation In Vitro.
AB  - Objective Chondrospheres represent a variant of tissue spheroids biofabricated
      from chondrocytes. They are already being used in clinical trials for cartilage
      repair; however, their biomechanical properties have not been systematically
      investigated yet. The aim of our study was to characterize chondrospheres in long
      term in vitro culture conditions for morphometric changes, biomechanical
      integrity, and their fusion and spreading kinetics. Results It has been
      demonstrated that the increase in chondrospheres secant modulus of elasticity is
      strongly associated with the synthesis and accumulation of extracellular matrix.
      Additionally, significant interplay has been found between biomechanical
      properties of tissue spheroids and their fusion kinetics in contrast to their
      spreading kinetics. Conclusions Extracellular matrix is one of the main
      structural determinants of chondrospheres biomechanical properties during
      chondrogenic maturation in vitro. The estimation of tissue spheroids' physical
      behavior in vitro prior to operative treatment can be used to predict and
      potentially control fusogenic self-assembly process after implantation in vivo.

PMID- 30221990
TI  - Seeing the child in context: Supporting gender diverse children and their
      families in multiple ways - An introduction to this special edition.
AB  - This Special Issue of Clinical Child Psychology and Psychiatry includes a group
      of papers that originated in the work of the Gender Identity Development Service
      (GIDS), which is the nationally designated National Health Service (NHS) in the
      United Kingdom to work with children and adolescents experiencing significant
      concern and distress about their gender. This short introduction to those papers
      aims to set the context and explain why certain areas have been given a focus.

PMID- 30221991
TI  - Intractable Facial Lesion.

PMID- 30221992
TI  - Value of IRB in Expanded Access.

PMID- 30221994
TI  - COPD patients in need of palliative care: Identification after hospitalization
      through the surprise question.
AB  - Currently, few patients suffering from chronic obstructive pulmonary disease
      (COPD) who might benefit from a palliative care approach are referred to a
      palliative care team. Tools to identify patients eligible for a palliative care
      approach have been found to be difficult to apply in daily practice. Therefore,
      there is need for a simple and easily applicable tool to identify those patients
      who would benefit from referral to a palliative care team. The aim of this study
      was to determine if the surprise question (SQ) "Would I be surprised if this
      patient dies within 12 months?" in a subset of recently hospitalized COPD
      patients identifies those subjects. Recently hospitalized COPD patients were
      included, and the answer to the SQ was provided by the treating pulmonologist.
      The gold standards framework (GSF) prognostic indicator guidance was regarded as
      the gold standard test and was assessed for each patient. Sensitivity,
      specificity, and negative and positive predictive values were calculated to
      determine the accuracy of the SQ plus recent hospitalization compared to the
      variables of the GSF. A total of 93 patients were analyzed. In 35 patients (38%),
      the answer to the SQ was "not surprised"; 78 patients (84%) met >=1 criteria of
      the GSF (15 (16%) did not meet any criteria). Specificity and positive predictive
      value for the SQ were both 100% ((78.2-100) and (87.7-100), respectively).
      Sensitivity was 44.9% (33.7-56.5) and negative predictive value was 25.9% (22.2
      29.9). The "not surprised" group fulfilled significantly more GSF criteria. The
      SQ after recent hospitalization for COPD has a very high specificity compared to
      a standardized tool and is therefore a useful tool for the quick identification
      of patients who are most likely to benefit from palliative care. However, this
      method doesn't identify all patients who are eligible for referral to palliative
      care.

PMID- 30221993
TI  - Rapid infusion rituximab is well tolerated in patients with primary CNS lymphoma.
AB  - AIM: To establish the safety and feasibility of rapidly infusing rituximab over
      90 min in patients with primary CNS lymphoma (PCNSL). PATIENTS & METHODS: We
      retrospectively reviewed all patients with PCNSL who received rapid rituximab
      infusions (RRI) from January 2016 to January 2017. Primary end point was
      incidence of infusion reactions. RESULTS & CONCLUSION: 11 patients received a
      total of 44 RRIs. Rituximab was dosed at 500 or 750 mg/m2. Premedication included
      acetaminophen and diphenhydramine. No infusion reactions occurred during any RRI.
      Two infusions were administered with steroids for neurologic symptoms at baseline
      (4.5%). Rapid administration of rituximab was safe and feasible for patients with
      PCNSL and at the higher doses received.

PMID- 30221995
TI  - Acral Lentiginous Melanoma: Survival Analysis of 715 Cases.
AB  - INTRODUCTION: Acral lentiginous melanoma (ALM) is an aggressive variant of
      melanoma; the incidence, prevalence, and prognosis differ among populations. We
      analyzed clinicopathological features and survival in Hispanics, a population
      with high ALM prevalence. MATERIAL AND METHODS: From 1144 patients with melanoma,
      we analyzed 715 ALMs and 429 non-ALMs from the National Referral Cancer Centre
      and compared survival. RESULTS: Of the ALM group, 62.8% were female; the median
      age was 58 years. The mean Breslow thickness was 3.56 +/- 7.16 mm. ALM patients
      showed an estimated 5-year disease-specific survival (DSS) of 53.3%, 52.7%, and
      40.8% for stage I, II, and III, respectively. For non-ALM patients, the DSS rates
      were 66%, 60.8%, and 48.4% for stage I, II, and III disease, respectively.
      Overall, the 1-, 3-, and 5-year DSS rates for patients with ALM were 85.1%,
      59.4%, and 46.3%, respectively; for non-ALM patients, they were 81.3%, 64.8%, and
      55.7%, respectively ( P = .168). In the multivariate analysis, factors associated
      with decreased DSS were high Breslow thickness, recurrence, ulceration, male sex,
      and advanced stage. CONCLUSIONS: The 1-, 3-, and 5-year DSS rates of patients
      with ALM were not statistically different from those of non-ALM patients. In
      addition to known adverse prognostic factors, male sex was also associated with
      worse survival.

PMID- 30221996
TI  - Soapbox: Technical, relational and relational-collaborative approaches to risk
      management.

PMID- 30221997
TI  - Training on the Use of Technology to Collect Patient-Reported Outcome Data
      Electronically in Clinical Trials: Best Practice Recommendations from the ePRO
      Consortium.
AB  - Electronic capture of patient-reported outcome (PRO) data has many advantages
      over paper-based data collection. Regulatory agencies have consistently supported
      the use of electronic PRO (ePRO) data capture and recommended participant and
      site staff training on the correct use of electronic data capture systems. The
      objective of this paper is to outline best practice recommendations for training
      end users, including site staff and study participants, on the use of ePRO
      technology in clinical trials to enable consistent, accurate, and complete data
      collection. Site personnel should be trained on study-specific as well as
      technology-specific topics and be given instructions on whom to contact to obtain
      technical support. Optimal training takes place over time using multiple
      modalities, including hands-on, face-to-face training at an investigator meeting
      or directly in the clinical site; remote training via webinar or teleconference;
      interactive on-demand self-paced-training via e-learning modalities; and
      supplemented by proxy training performed by study clinical research associates.
      Like site personnel training, study participants should be provided with
      individual, hands-on training by site staff at the initiation of the trial and in
      conjunction with interactive electronic training modules that can be accessed on
      demand throughout the duration of the trial. The recommendations put forth in
      this paper provide a structured framework for the training that site personnel
      and study participants need to optimize the advantages trials can gain from using
      ePRO data collection systems.

PMID- 30221998
TI  - Prescribing Home Narrowband UVB Phototherapy: A Review of Current Approaches.
AB  - Conventional, full-body phototherapy equipment is costly and therefore patients
      are usually treated in dermatology centres. Such office-based therapy is often
      not feasible for those patients who live far away from a phototherapy centre due
      to lost time and wages, inability to travel because of extensive skin disease, or
      prohibitive travel costs. Home phototherapy has emerged as a modality that meets
      the needs of those patients. Our aim was to review available studies on UV
      sources, treatment protocols, efficacy, and safety of home phototherapy. A
      literature review was conducted on PubMed using the terms "home" AND
      "phototherapy" AND ("guide" OR "approach" OR "review" OR "protocol"). From the
      data extracted, narrowband UVB (311 nm) offers the best balance between safety
      and efficacy and is recommended for home phototherapy by most authors. Treatment
      is safe and possible adverse effects are related to overexposure (erythema,
      blistering). The usual treatment protocol was administering treatments on
      alternating days, including weekends, with dosing based on the patient's
      Fitzpatrick skin type. We also provide information on the available home
      phototherapy systems in Canada and their reimbursement. Home phototherapy is
      underused in Canada. Narrowband UVB phototherapy sources equipped with a 3
      dimensional panel provides a practical and safe option.

PMID- 30221999
TI  - The Interactive Effect of Positive Mental Health and Subjective Sleep Quality on
      Depressive Symptoms in High School Students.
AB  - OBJECTIVE/BACKGROUND: The objective of this study was to observe the effect of
      positive mental health (PMH) and subjective sleep quality (SQ) on depressive
      symptoms in high school students. PARTICIPANTS: This cross-sectional study
      evaluated 2,186 students (55% female and 45% male) with a mean age of 16.8 years
      (SD +/- 0.7) at 20 private high schools in Mexico City. METHODS: An electronic
      survey was used, which included a questionnaire on sleep habits that is a Spanish
      language adaptation of Rosenthal's Sleep-Wake Activity Inventory, the Pittsburgh
      Sleep Quality Index (PSQI), the Morningness-Eveningness Scale for Children and
      Adolescents (MESC), the combined scales to evaluate positive aspects of mental
      health, and the Patient Health Questionnaire (PHQ-9). RESULTS: Main and
      interaction effects of PMH and SQ were observed, demonstrating that students with
      high-PMH (p <= .0001) or good-SQ (p <= .0001) had fewer depressive symptoms.
      Thus, the students with both high-PMH and good-SQ had the lowest depressive
      symptomatology (p <= .01). CONCLUSION: Depressive symptoms are associated with a
      combination of sleep quality and positive mental health.

PMID- 30222000
TI  - Analysis of "Capillary and Venous Blood Glucose Accuracy in Blood Glucose Meters
      Versus Reference Standards: The Impact of Study Design on Accuracy Evaluations".
AB  - The article by Macleod and coauthors outlines an accuracy study of two blood
      glucose monitoring systems (BGMSs) against glucose-oxidase- and hexokinase-based
      assays showing how the reference/comparison method and inappropriate sample
      comparisons can affect accuracy conclusions. The dangers of independent
      institutions producing inappropriate conclusions when the methodology used for
      product regulatory or registration accuracy requirements is not according to best
      practice are stressed. The authors highlight several important aspects of a
      multistep accuracy evaluation protocol. However, it is essential that anyone
      undertaking or reporting BGMS accuracy studies should have a clear understanding
      of each and every protocol point, best practice, and how each can influence
      accuracy conclusions. Claims against regulatory accuracy criteria should be made
      only if the detailed specified protocol design and analysis is followed.

PMID- 30222001
TI  - Noninvasive Monitoring of Blood Glucose Using Color-Coded Photoplethysmographic
      Images of the Illuminated Fingertip Within the Visible and Near-Infrared Range:
      Opportunities and Questions.
AB  - Noninvasive blood glucose assays have been promised for many years and various
      molecular spectroscopy-based methods of skin are candidates for achieving this
      goal. Due to the small spectral signatures of the glucose used for direct
      physical detection, moreover hidden among a largely variable background, broad
      spectral intervals are usually required to provide the mandatory analytical
      selectivity, but no such device has so far reached the accuracy that is required
      for self-monitoring of blood glucose (SMBG). A recently presented device as
      described in this journal, based on photoplethysmographic fingertip images for
      measuring glucose in a nonspecific indirect manner, is especially evaluated for
      providing reliable blood glucose concentration predictions.

PMID- 30222002
TI  - Inactivation of Lactobacillus Virulent Bacteriophage by Thermal and Chemical
      Treatments.
AB  - The uses of thermal and chemical treatments were evaluated with respect to the
      inactivation of the Lactobacillus virulent bacteriophage P2. Thermal treatments
      consisted of heating the phage at 63, 72, and 90 degrees C in three broth media:
      de Man Rogosa Sharpe broth, reconstituted skim milk, and Tris magnesium gelatin
      buffer. Chemical treatments evaluated were ethanol, isopropanol, sodium
      hypochlorite, and peracetic acid at various concentrations. Phage P2 was
      completely inactivated in 20 and 5 min at 72 and 90 degrees C, respectively.
      Reconstituted skim milk and de Man Rogosa Sharpe broth provided optimum and
      minimum heat protection, respectively. Only sodium hypochlorite at 400 and 800
      ppm completely inactivated the phage in 50 and 30 min, respectively. Treatment
      with 100% ethanol and isopropanol resulted in only a ca. 5.1-log reduction.
      Peracetic acid at the highest concentration used (0.45%) resulted in only a 1.40
      log reduction of the phage within 60 min. These results provide additional data
      for establishing effective methods of controlling phage contamination in dairy
      and laboratory environments.

PMID- 30222003
TI  - Understanding Why Frequent Users of EMS Call 9-1-1: A Grounded Theory Study.
AB  - INTRODUCTION: Frequent users of emergency medical services (EMS) have
      disproportionately high 9-1-1 call frequency. Evidence suggests that this small
      group burdens the health care system, leading to misallocation of already-limited
      health resources. AIM: To understand frequent users' perceptions and experiences
      regarding EMS, as well as the driving factors underlying their frequent use.
      METHOD: A grounded theory approach guided our qualitative research process.
      Participants older than 17 years who called EMS five or more times in the past
      year were consecutively sampled where each participant was contacted in the order
      they appeared on our list of potential participants for interviews until data
      saturation was achieved. Transcripts were analyzed to derive common themes among
      frequent EMS callers. RESULTS: Frequent EMS calls often resulted from chronic
      medical conditions creating recurrent crisis situations, mental health issues as
      well as mobility issues, frequent noninjurious falls, and social isolation.
      Combined with these factors, perceptions of the purpose of EMS and social
      circumstances also contributed to the creation of complex health issues that
      influenced frequent EMS use. These findings can advise the development of future
      paramedicine programs and health promotion interventions.

PMID- 30222004
TI  - Model Implied Instrumental Variables (MIIVs): An Alternative Orientation to
      Structural Equation Modeling.
AB  - Few dispute that our models are approximations to reality. Yet when it comes to
      structural equation models (SEMs), we use estimators that assume true models
      (e.g. maximum likelihood) and that can create biased estimates when the model is
      inexact. This article presents an overview of the Model Implied Instrumental
      Variable (MIIV) approach to SEMs from Bollen (1996). The MIIV estimator using Two
      Stage Least Squares (2SLS), MIIV-2SLS, has greater robustness to structural
      misspecifications than system wide estimators. In addition, the MIIV-2SLS
      estimator is asymptotically distribution free. Furthermore, MIIV-2SLS has
      equation-based overidentification tests that can help pinpoint misspecifications.
      Beyond these features, the MIIV approach has other desirable qualities. MIIV
      methods apply to higher order factor analyses, categorical measures, growth curve
      models, dynamic factor analysis, and nonlinear latent variables. Finally, MIIV
      2SLS permits researchers to estimate and test only the latent variable model or
      any other subset of equations. In addition, other MIIV estimators beyond 2SLS are
      available. Despite these promising features, research is needed to better
      understand its performance under a variety of conditions that represent empirical
      applications. Empirical and simulation examples in the article illustrate the
      MIIV orientation to SEMs and highlight an R package MIIVsem that implements MIIV
      2SLS.

PMID- 30222005
TI  - Scleral Cross-Linking Using Glyceraldehyde for the Prevention of Axial Elongation
      in the Rabbit: Blocked Axial Elongation and Altered Scleral Microstructure
      Scleral Cross-Linking Using Glyceraldehyde.
AB  - BACKGROUND: This study aims to assess the efficacy of the scleral collagen cross
      linking method using glyceraldehyde solution for prevention of lens-induced axial
      elongation in New Zealand rabbits and investigate the biochemical and
      microstructural changes that occur. METHODS: The right eyes of New Zealand
      rabbits aged seven weeks were randomly divided into three groups: the cross
      linking group (n = 6), non-crosslinking group (n = 5), and untreated control
      group (n = 5). Eyes in cross-linking and non-crosslinking groups were treated
      with a -8.00 Diopter spherical lens over the course of two weeks. The cross
      linking effects were achieved by a sub-Tenon's injection of 0.15 ml 0.5 M
      glyceraldehyde to eyes in the CL group. Ocular parameters were measured on the
      1st, 7th, and 14th days. Biomechanical testing, light and electronic microscopy
      were used. RESULTS: Following the cross-linking treatment, eyes in the cross
      linking group had a shorter axial length compared to those in the non
      crosslinking group (p = 0.006). Collagen fibrils larger than 240 nm were observed
      in the scleral stroma of cross-linking group, which were absent in the scleral
      stroma of the non-crosslinking and untreated control group. The mean ultimate
      stress and Young's modulus was significantly greater in the cross-linking group
      compared to those in the non-crosslinking and untreated control group (p < 0.05).
      No histological damage observed in the retina or choroid. CONCLUSIONS: This study
      demonstrates that lens-induced axial elongation in rabbits can be effectively
      blocked by cross-linking using glyceraldehyde, with anatomical and mechanical
      modification and no deleterious effects.

PMID- 30222006
TI  - The Use of Recommendations on Physician Rating Websites: The Number of Raters
      Makes the Difference When Adjusting Decisions.
AB  - Physician rating websites allow users to check physicians' profiles, write
      reviews, or rate their performance. The opinion of other users regarding a
      physician can affect our decision to visit her/him. To investigate the specific
      role of the number of users rating a physician when choosing a physician with
      support of these platforms, we used a Judge-Advisor System in which participants
      answered their likelihood to visit a physician before and after seeing the
      recommendations of others. Within the experiment, three conditions were
      presented: high and low number of reviewers recommending a physician, and no
      recommendations. We found that the participants' likelihood to visit a physician
      varied with respect to the displayed physician characteristics on the platform.
      Importantly, after the recommendation of others was presented, participants'
      likelihood to visit the physician changed significantly. The participants'
      adjusted response was significantly closer to the recommendation coming from a
      higher number of users, which indicate that this online, social media cue
      influences our decision to visit physicians. Comments and ratings on physician
      ratings are generally positive, but we show that negative ratings have a direct
      negative influence in the decision to visit a physician. We suggest
      administrators of these platforms to pay special attention to the content that
      users upload.

PMID- 30222007
TI  - Alignments and differentiations: People with illness experiences seeking
      legitimate positions as health service developers and producers.
AB  - Health policies and strategies promote the involvement of people with illness
      experiences in service development and production, integrating them into settings
      that have traditionally been domains of health professionals. In this study, we
      focus on the perspectives of people with personal illness experiences and explore
      how they justify involvement, position themselves as legitimate actors and forge
      collaborative relationships with health professionals. We have used discourse
      analysis in analysing individual interviews conducted with peer support workers
      and experts by experience (n = 17) who currently work in Finnish health services.
      The interviewees utilised discourses of empowerment, efficiency and patient
      centeredness, aligning themselves with the justifications constructed by patient
      movements additionally to those found in current health policies. Both groups
      wanted to retain critical distance from professionals in order to voice
      criticisms of current care practices, yet they also frequently aligned themselves
      with professionals in order to gain legitimacy for their involvement. They
      adopted professional traits that moved them further from being lay participants
      sharing personal experiences and adopted an expert position. Although national
      level policies provided backing and legitimacy for involvement, the lack of local
      level guidance could hinder the practical implementation and make involvement
      largely dependent of professionals' discretion.

PMID- 30222008
TI  - Alpha-1 chain of human haptoglobin as viability marker of in vitro fertilized
      human embryos: information beyond morphology.
AB  - : Only one third of the in vitro fertilization treatments result in successful
      delivery following morphological viability assessment worldwide. A paper by
      Montsko et al. (2015) describes the identification of the alpha-1 chain of human
      haptoglobin as a potential marker of embryo viability. Using mass spectrometry,
      the concentration of the haptoglobin alpha-1 chain was determined in spent
      culture media samples of in vitro fertilized embryos and correlation was found
      with the outcome of the respective transfer. In the present study we
      investigated, whether the concentration of haptoglobin alpha-1 chain shows any
      correlation with morphological scores to clarify whether levels of the alpha-1
      chain provide additional information on embryo viability unnoticed by the
      morphological assessment. In the study, pregnancy and live birth rates were
      examined in 143 transferred samples of 86 patients, retrospectively. Two sample
      groups were created. The control group contained embryos classified as 'good' or
      'fair' based on the Istanbul Consensus Criteria System, while the double-assay
      group contained embryos assessed as 'good' or 'fair' by the morphological
      evaluation and as 'viable' by the haptoglobin assay. Clinical pregnancy rate was
      30.2% in the control group, while 47.6% in the group scored parallel with
      morphological criteria and proteomic analysis (p < 0.05). The increased clinical
      pregnancy rate observed in the double-assayed group can be attributed to
      decreased false-positivity of the double assay. ABBREVIATIONS: IVF: in vitro
      fertilization; SEC: spent embryo culture medium; HSA: human serum albumin; Hpt:
      haptoglobin; HptA1: haptoglobin alpha-1 chain; ICCS: Istanbul Consensus Criteria
      System; BMI: body mass index; ICSI: intracytoplasmic sperm injection.

PMID- 30222009
TI  - Exploring young people's emotional well-being and resilience in educational
      contexts: A resilient space?
AB  - The term 'resilience' is pervasive in narratives of young people's emotional well
      being. However, the meaning it has for those it describes is perhaps less well
      understood. Resilience was investigated as part of an engagement exercise into
      health improvement commissioning in educational contexts in the South East of
      England. One hundred and nine young people in total were involved, and this
      article reports data collected from two areas that were explored, comprising a
      sub-set of 58 participants: emotional well-being and resilience (n = 23) and the
      whole school approach (n = 35). It was apparent that while not all participants
      engaged with the term 'resilience' itself, they nevertheless often adopted
      creative individual and collective strategies to protect and enhance their
      emotional well-being. Furthermore, participants reported a sense of resilience
      that arose from a shared sense of adversity that helped strengthen collective
      support and solidarity, thus supporting previous work on emergent collective
      resilience. Theoretical and practical implications are discussed, along with a
      recommendation for more participatory research, so that young people can be more
      confident that their views are being considered within such exercises.

PMID- 30222010
TI  - Solidarity after nature: From biopolitics to cosmopolitics.
AB  - What is sustaining the divide between nature and nurture, even though sciences
      like epigenetics have been challenging it for at least two decades? Evelyn Fox
      Keller asked this question and considered it a logical problem rooted in
      terminological confusion within the sciences. In this article, we propose a
      complementary diagnosis of the problem: the nature-nurture divide is (re
      )mobilized when society faces questions of inclusion and solidarity. With
      examples stemming from the fields of insurance and health care, immigration
      policy and epigenetics, we demonstrate how the nature-nurture divide is performed
      through techniques of classification for a politics of solidarity. We identify a
      common operation to these different examples that we coin 'biopolitical
      imputation'. We use this term to draw attention to how (Western) societal
      institutions, including science, create solvable problems out of complex
      situations, defining human actors and their agency along the lines of the nature
      nurture divide as a moral guide. We argue that the tenacity of the nature-nurture
      divide is therefore not only a logical problem needing better scientific
      concepts, but also a cosmopolitical problem asking for a more profound reflection
      on the ontology and ethics of solidarity in order to move beyond the biopolitics
      of nature versus nurture.

PMID- 30222011
TI  - Current developments in pharmacotherapy for actinic keratosis.
AB  - INTRODUCTION: Actinic keratosis (AK) is a superficial squamous cell carcinoma
      (SCC) where chronic sun exposure playing central role in its pathogenesis. UVB
      causes direct damage to DNA, producing pyrimidine dimers, and suppressing the
      protective role of p53. The stepwise progression of AK, with increased expression
      of anti-apoptotic Bcl-2, favors progression to SCC. Moreover, the dermal response
      characterized by inflammation and mediated by prostaglandins is a critical
      component of tumorigenesis that promotes tumor growth, tissue invasion,
      angiogenesis and metastasis. Other risk factors are represented by age, gender,
      phototype and drugs. Areas covered: In this review, the authors document the
      recent developments of different therapies used to treat AK and provide their
      perspectives on current and future treatment strategies. Expert opinion: The
      usefulness of long-term treatment with piroxicam and sun filters or diclofenac
      targeting the inflammation phases of skin tumorigenesis favors AK's healing and
      provides greater control of the cancerization field. Nonsteroidal anti
      inflammatory drugs can be safely used in patients who use photosensitizing drugs
      and, therefore, are more at risk of developing skin tumors. Immunomodulatory
      therapies, which require shorter treatment, are characterized by more common
      local side effects, and need more attention by the dermatologist in the concern
      of patient education, resulting essential to improve adherence and outcomes.

PMID- 30222012
TI  - Rebound of atopic dermatitis as a complication of using systemic glucocorticoids;
      a myth or a fact?

PMID- 30222013
TI  - Retained surgical needle and gauze after cesarean section and adnexectomy: a case
      report and literature review.
AB  - Although the incidence of retained surgical items (RSIs) is low, it is
      nevertheless an important preventable cause of patient injury that can ultimately
      lead to the patient's death and to subsequent high medical and legal costs.
      Unintentional RSI is the cause of 70% of re-interventions, with a morbidity of
      80% and mortality of 35%. The most common RSIs are sponges or gauze (gossypiboma
      or textiloma), while retained surgical instruments and needles are rare.
      Perioperative counting of equipment and materials is the most common method of
      screening for RSIs, while a diagnosis can later be confirmed by the clinical
      appearance and by imaging studies. We present a rare case of a 43-year-old
      patient who was admitted to our hospital because of two retained needles
      following a cesarean section, despite several subsequent laparotomies. One needle
      had been removed previously, but in addition to the remaining needle, we also
      removed a retained gauze. The diagnosis of RSIs is extremely important, and safe
      surgical practices including the addition of new imaging technologies should be
      encouraged to detect RSIs.

PMID- 30222014
TI  - Recent advances in molecular testing to improve early diagnosis in children with
      mucopolysaccharidoses.
AB  - INTRODUCTION: The mucopolysaccharidoses (MPS) are a group of lysosomal storage
      disorders with high phenotypic and genotypic heterogeneity, making precise
      diagnosis challenging. Although enzyme activity assay is considered the gold
      standard for the diagnosis of these disorders, molecular testing can greatly
      refine this task. New methods for rapid detection of variants are useful to
      reduce the 'diagnostic odyssey' faced by patients and their family, to lead to
      appropriate genetic counseling and to select the most appropriate therapy for
      each case. Areas covered: We review and discuss the advantages, disadvantages and
      limitations of the modern technologies in the field of molecular diagnosis of
      MPS, presenting our own experience. Expert commentary: While current molecular
      genetics testing for MPS mostly relies on PCR and Sanger sequencing, promising
      alternative techniques have emerged over the last few years, and its application
      into routine clinical practice is gaining momentum.

PMID- 30222016
TI  - Acute cardiac dyspnea in the emergency department: diagnostic value of N-terminal
      prohormone of brain natriuretic peptide and galectin-3.
AB  - Objective This study was performed to determine whether a dual-biomarker approach
      using N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and galectin
      3 optimizes the diagnosis and risk stratification of acute cardiac dyspnea.
      Atypical clinical manifestations and overlapping pathologies require objective
      and effective diagnostic methods to avoid treatment delays. Methods This
      prospective observational study included 208 patients who presented to the
      emergency department for acute dyspnea. NT-proBNP and galectin-3 were measured
      upon admission. The patients were divided into two groups according to the
      etiology of their clinical manifestations: cardiac and non-cardiac dyspnea. The
      patients' New York Heart Association functional class, left ventricular ejection
      fraction, and discharge status were assessed. Results Diagnostic criteria for
      acute heart failure were fulfilled in 61.1% of the patients. NT-proBNP and
      galectin-3 were strongly and significantly correlated. Receiver operating
      characteristic analysis revealed similar areas under the curve for both markers
      in the entire group of patients as well as in the high-risk subsets of patients.
      Conclusions The diagnostic performance of NT-proBNP and galectin-3 is comparable
      for both the total population and high-risk subsets. Galectin-3 adds diagnostic
      value to the conventional NT-proBNP in patients with acute cardiac dyspnea, and
      its utility is of major interest in uncertain clinical situations.

PMID- 30222015
TI  - Unhealthy Behaviors Among Canadian Men Are Predictors of Comorbidities:
      Implications for Clinical Practice.
AB  - Men's poor health behaviors are an increasingly prevalent issue with long-term
      consequences. This study broadly samples Canadian men to obtain information
      regarding health behaviors as a predictor of downstream medical comorbidities. A
      survey of Canadian men included questions regarding demographics, comorbidities,
      and health behaviors (smoking and alcohol consumption, sleep and exercise
      behaviors, and dietary habits). Health behaviors were classified as either
      healthy or unhealthy based upon previous studies and questionnaire thresholds.
      Multivariate regression was performed to determine predictors for medical
      comorbidities. The 2,000 participants were aged 19-94 (median 48, interquartile
      range 34-60). Approximately half (47.4%) were regular smokers, 38.7% overused
      alcohol, 53.9% reported unhealthy sleep, 48.9% had low levels of exercise, and
      61.8% had unhealthy diets. On multivariate analysis, regular smoking predicted
      heart disease (OR 2.08, p < .01), elevated cholesterol (OR 1.35, p = .02), type 2
      diabetes (OR 1.57, p = .02), osteoarthritis (OR 1.43, p = .04), and depression
      (OR 1.62, p < .01). Alcohol overuse predicted hypertension (OR 1.40, p < .01) and
      protected against type 2 diabetes (OR 0.61, p < .01). Unhealthy sleep predicted
      hypertension (OR 1.46, p < .01), erectile dysfunction (OR 1.50, p = .04), and
      depression (OR 1.87, p < .01). Low levels of exercise predicted hypertension (OR
      1.30, p = .03) and elevated cholesterol (OR 1.27, p = .05). Finally, unhealthy
      diet predicted depression (OR 1.65, p < .01). This study confirms the association
      of poor health behaviors and comorbidities common to middle-aged and older men.
      The results emphasize the potential scope of targeted gender-sensitized public
      awareness campaigns and interventions to reduce common male disease, morbidity,
      and mortality.

PMID- 30222017
TI  - A practical algorithm for topical treatment of atopic dermatitis in the Middle
      East emphasizing the importance of sensitive skin areas.
AB  - Background There is a need for safe, effective treatment for atopic dermatitis
      (AD) in the Middle East. Objective To propose a practical algorithm for the
      treatment of AD throughout the Middle East. Methods An international panel of six
      experts from the Middle East and one from Europe developed the algorithm. The
      practical treatment guide was based on a review of published guidelines on AD, an
      evaluation of relevant literature published up to August 2016 and local treatment
      practices. Results Patients with an acute mild-to-moderate disease flare on
      sensitive body areas should apply the topical calcineurin inhibitor (TCI),
      pimecrolimus 1% cream twice daily until clearance. For other body locations, a
      TCI, either pimecrolimus 1% cream, tacrolimus 0.03% ointment in children or 0.1%
      ointment in adults, should be applied twice daily until clearance. Emollients
      should be used as needed. Patients experiencing acute severe disease flares
      should apply a topical corticosteroid (TCS) according to their label for a few
      days to reduce inflammation. After clinical improvement, pimecrolimus for
      sensitive skin areas or TCIs for other body locations should be used until there
      is a complete resolution of lesions. Conclusions These recommendations are
      expected to optimize AD management in patients across the Middle East.

PMID- 30222018
TI  - Assessing the Quality of Nursing Homes in Managed Care Organizations: Integrating
      LTSS for Dually Eligible Beneficiaries.
AB  - Little is known about the quality of nursing homes in managed care organizations
      (MCOs) networks. This study (1) described decision-making criteria for selecting
      nursing home networks and (2) compared selected quality indicators of network and
      nonnetwork nursing homes. The sample was 17 MCOs participating in a California
      demonstration that provided integrated long-term services and supports to dually
      eligible enrollees in 2017. The findings showed that the MCOs established a broad
      network of nursing homes, with only limited attention to using quality criteria.
      Network nursing homes (602) scored significantly lower on 6 selected quality
      measures than nonnetwork (117) nursing homes. Low registered nurse and total
      nurse staffing were strong predictors of network nursing homes controlling for
      facility characteristics. Managed care organizations should consider greater
      transparency about the quality of their nursing homes and use specific quality
      criteria to improve the quality of their networks.

PMID- 30222019
TI  - Paucity of Interlobular Bile Ducts in Multidrug-Resistant P-Glycoprotein 3 (MDR3)
      Deficiency.
AB  - Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator
      encoded by the ABCB4 gene located on chromosome 7. MDR3 mediates the
      translocation of phosphatidylcholine across the canalicular membrane of the
      hepatocyte into bile. Severe MDR3 deficiency typically occurs during childhood
      with progressive cholestasis evolving to cirrhosis and liver failure, requiring
      liver transplantation. In this article, we report 2 pediatric cases of severe
      MDR3 deficiency with paucity of interlobular bile ducts. Both underwent living
      donor liver transplantation at our center for decompensated liver disease and
      portal hypertension. We diagnosed severe MDR3 deficiency in both the cases with
      negative MDR3 immunostaining in the explanted liver. Genetic studies revealed
      homozygous deletion single base pair deletion in exon 24 of the ABCB4 gene in the
      second child. The patients are on regular follow-up after liver transplant and
      are doing well. Our report highlights that cholangiopathy in MDR3 deficiency can
      lead to ductopenia in pediatric livers.

PMID- 30222020
TI  - Interdigitating dendritic cell sarcoma located in the groin: a case report and
      literature review.
AB  - Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare subtype of
      dendritic cell neoplasms, and current knowledge on this tumor is limited. We
      herein report a case of an IDCS in a 64-year-old man who presented with a right
      inguinal mass combined with extensive retroperitoneal, pulmonary, hepatic, renal,
      and bone marrow infiltration. Because of the advanced stage of the disease, we
      performed five cycles of chemotherapy, including cyclophosphamide, doxorubicin,
      vincristine, and prednisone (CHOP); doxorubicin, bleomycin, vinblastine, and
      dacarbazine (ABVD); and ABVD combined with cisplatin, and one cycle of
      radiotherapy. The patient's inguinal mass became smaller during the treatment,
      but there was no change in the extent of infiltration at the other sites. The
      patient died 8 months after the initial diagnosis. We also herein review the
      etiology, diagnosis, differential diagnosis, treatment, and prognosis of IDCS,
      and analyze the characteristics of IDCS in Chinese patients.

PMID- 30222022
TI  - Association between expression of TNF-alpha, P53 and HIF1alpha with
      asthenozoospermia.
AB  - Reduced sperm motility (asthenozoospermia) accounts for a significant percentage
      of male infertility and numerous factors have been suggested to explain this
      phenomenon among which hypoxic and inflammatory markers are the least studied.
      Therefore, the aim of this study was to assess the main molecular markers
      involved in hypoxia (P53 and HIF-1alpha) and inflammation (TNF-alpha) pathways in
      infertile men with asthenozoospermia. Expression of these markers were assessed
      by qRT-PCR, and analysis of data show that mean of hypoxia markers (P53, HIF
      1alpha) and also TNF- alpha were significantly higher in infertile men with
      asthenozoospermia compared to fertile men (p < 0.05). Unlike TNF-alpha,
      significant negative correlations were observed between expression of P53 (r = 
      0.568; p = 0.002) and HIF-1alpha (r = -0.403; p = 0.046) with sperm motility. In
      addition, a significant negative correlation was observed between expression of
      P53 with sperm concentration (r = -0.576; p < 0.001). In addition, a significant
      positive correlation was observed between hypoxia markers (P53, HIF-1alpha) and
      TNF-alpha (p < 0.01). However, no significant relation was observed between TNF
      alpha and semen parameters. Taken together, the results of this study suggest the
      involvement of hypoxia pathway is more pronounced than the inflammatory pathway
      in asthenozoospermia.

PMID- 30222021
TI  - A comparison of diagnosis of early stage interproximal caries with bitewing
      radiographs and periapical images using consensus reference.
AB  - OBJECTIVES:: The purpose of this study was to assess the diagnostic property of
      intraoral bitewing radiographs (BTW) for early stage interproximal caries, and to
      compare them with periapical radiographs (PA) at different levels of caries
      progression. METHODS:: A total of 241 interproximal surfaces of BTW and
      corresponding PAs were used. Seven teaching faculty consisting of three oral and
      maxillofacial radiologists, two operative faculty, and two prosthodontists
      evaluated the images. The observers graded images as either "intact", "enamel
      caries <1/2 width", "enamel caries >1/2 width", or "caries into dentin". The gold
      standard was established by consensus of two experienced faculty with 35 years
      and 27 years of experience. Specificity, sensitivity, positive-predictive value,
      and negative-predictive value were calculated for the different level of caries
      progression. Furthermore, receiver operating curves) of BTW and PAs of each
      evaluator were made and the area under the curve of BTW and PAs were compared.
      RESULTS:: There was no significant difference in the specificity of BTW and PAs.
      BTW showed significantly higher sensitivity than PAs in all levels of caries
      progression (p<0.01). Positive-predictive value and negative-predictive value of
      BTWs were also significantly higher than PAs. One-way ANOVA and Tukey HSD test
      showed a significant difference in sensitivity with different levels of caries
      progression. The average area under the curve was significantly higher for BTWs
      than PAs (p<0.01). CONCLUSIONS:: BTWs offer a significant advantage over PAs in
      the diagnoses of early stages of interproximal carious lesions.

PMID- 30222023
TI  - Composite Paraganglioma: Pioneering in the Head and Neck.
AB  - Composite paragangliomas are rare with less than 20 cases documented in the
      abdomen, retroperitoneum, and urinary bladder. In this article, we report the
      first case of composite paraganglioma in the head and neck presenting as a soft
      tissue mass in the neck adjacent to the carotid artery in a 50-year-old woman. We
      discuss the clinicopathologic findings and genetic implications, and we review
      the literature of this rare entity.

PMID- 30222024
TI  - A novel missense mutation in BEST1 associated with an autosomal-dominant
      vitreoretinochoroidopathy (ADVIRC) phenotype.
AB  - BACKGROUND: To report a 68-year-old female with an autosomal-dominant
      vitreoretinochoroidopathy (ADVIRC) phenotype associated with a subretinal
      hemorrhage (SRH) and novel BEST1 pathogenic variation p.Met571Thr. MATERIALS AND
      METHODS: The patient was assessed by fundus photography, fluorescence and
      indocyanine green angiography, spectral-domain optical coherence tomography,
      photopic and scotopic electroretinogram (ERG), and electrooculogram (EOG). Whole
      exome and Sanger sequencing of the patient's and selected family members' DNA was
      performed. Ophthalmoscopic examinations were also performed on six patient's
      relatives. RESULTS: The patient presented moderate vitreous and SRH in the left
      eye. A distinct, annular hyperpigmented band was present in both eyes. Vitrectomy
      improved visual acuity, and the SRH gradually regressed without recurrence.
      Preserved macular function was shown by optical coherence tomography (OCT).
      Genetic analysis identified a novel heterozygous mutation, resulting in
      p.Met571Thr in BEST1. No mutations were observed in a panel of other eye disease
      genes, suggesting that this pathogenic variation in BEST1 is associated with an
      ADVIRC phenotype. No other evaluated family member had the variant or the fundus
      findings. CONCLUSIONS: We present a patient with a novel p.Met571Thr pathogenic
      variation associated with an ADVIRC phenotype. SRH is a unique finding in ADVIRC
      patients and may correspond to peripheral exudative hemorrhagic
      chorioretinopathy. The BEST1 pathogenic variation p.Met571Thr might be the likely
      cause of ADVIRC in this patient. However, further study is necessary to determine
      whether this mutation is causative.

PMID- 30222025
TI  - Factors impeding the effective utilisation of an electronic patient report form
      during handover from an ambulance to an emergency department.
AB  - We investigated the reasons why the transition from paper to electronically
      formatted records during patient handover between ambulance crews and emergency
      department staff in a North East England Emergency Department has not always been
      viewed positively. Interviews with seven paramedics and three emergency
      department staff were conducted in addition to observations of 74 ambulance staff
      during 37 handovers in the emergency department. In just over half of the
      handovers (20), paramedics found it necessary to provide written information to
      aid emergency department staff, in addition to that recorded electronically.
      There were a number of issues that impeded the ready utilisation of electronic
      records in this context. The major factors identified as contributing to this
      were the choice of system architecture, the design of user interfaces, and the
      procurement process used by the National Health Service. We have made some
      suggestions about how the system could evolve from one focused on providing
      management information to one that also supports operational needs.

PMID- 30222026
TI  - Childhood Conditions Predict Chronic Diseases and Functional Limitations Among
      Older Adults: The Case of Indonesia.
AB  - OBJECTIVE: Limited knowledge exists about whether childhood health and
      socioeconomic status (SES) conditions influence health among older adults in
      Indonesia. METHOD: Data from Wave 5 (2014/2015) of the Indonesian Family Life
      Survey ( N = 6,530) was used to examine associations between childhood health and
      SES and hypertension, lung conditions, diabetes, lower body functional
      limitations (LBFL), and instrumental activities of daily living limitations
      (IADL). RESULTS: Poor childhood health was associated with 34% higher odds of
      hypertension (odds ratio [OR] = 1.34, p < .05), 37% higher odds of diabetes (OR =
      1.37, p < .05), and 32% higher odds of lung conditions (OR = 1.32, p < .05).
      Household overcrowding was associated with 22% higher odds of a LBFL (OR = 1.22,
      p < .05) and 24% higher odds of an IADL (OR = 1.24, p < .01). Lacking a household
      toilet was associated with 18% higher odds of a LBFL (OR = 1.18, p < .05).
      Adjusting for adult SES and current health did not account for these
      relationships. DISCUSSION: Childhood conditions appear to shape older adult
      health in Indonesia.

PMID- 30222027
TI  - Attention in Children With Autism Spectrum Disorder and the Effects of a
      Mindfulness-Based Program.
AB  - OBJECTIVE: Children with autism spectrum disorder (ASD) show atypical attention.
      Mindfulness-based programs (MBPs), with self-regulation of attention as a basic
      component, could benefit these children. METHOD: We investigated how 49 children
      with ASD differed from 51 typically developing (TD) children in their attention
      systems; and whether their attention systems were improved by an MBP for children
      and their parents (MYmind), using a cognitive measure of attention, the Attention
      Network Test. RESULTS: Children with ASD did not differ from TD children in the
      speed of the attention systems, but were somewhat less accurate in their
      orienting and executive attention. Also, MYmind did not significantly improve
      attention, although trend effects indicated improved orienting and executive
      attention. Robustness checks supported these improvements. CONCLUSION: Trend
      effects of the MBP on the attention systems of children with ASD were revealed,
      as well as minor differences between children with ASD and TD children in their
      attention systems.

PMID- 30222028
TI  - Adult Acute Lymphoblastic Leukemia: Limitations of Intensification of Therapy in
      a Developing Country.
AB  - Purpose Limited data exist on intensifying chemotherapy regimens in the treatment
      of adult acute lymphoblastic leukemia (ALL) outside the setting of a clinical
      trial. Materials and Methods Retrospectively, data from 507 consecutive adults
      (age >= 15 years) with a diagnosis of ALL treated at our center were analyzed.
      Standard-risk (SR) patients were offered treatment with a modified German
      Multicenter ALL (GMALL) regimen, whereas high-risk (HR) patients were offered
      intensification of therapy with hyperfractionated cyclophosphamide, vincristine,
      doxorubicin, and dexamethasone (HCVAD). Because of resource constraints, a
      proportion of HR patients opted to receive the same treatment regimen as used for
      SR patients. Results There were 344 SR patients (67.8%) and 163 HR patients
      (32.2%) at diagnosis. Among the HR patients, 53 (32.5%) opted to receive
      intensification with the HCVAD regimen. The SR cohort showed a superior 5-year
      event-free survival rate compared with the HR cohort (47.3% v 23.6%,
      respectively; P < .001). Within the HR subgroup, there was no statistically
      significant difference in overall survival or event-free survival between
      patients who received the modified GMALL regimen (n = 59) and patients who
      received HCVAD (n = 53). Conclusion Intensified therapy in the HR subset was
      associated with a significant increase in early treatment-related mortality and
      cost of treatment. A modified GMALL regimen was found to be cost-effective with
      clinical outcomes comparable to those achieved with more intensive regimens.

PMID- 30222029
TI  - Men With a "Woman's Disease": Stigmatization of Male Breast Cancer Patients-A
      Mixed Methods Analysis.
AB  - Male breast cancer (MBC) is rare and known as a typical woman's disease. This
      study is part of the N-MALE project (Male breast cancer: patient's needs in
      prevention, diagnosis, treatment, rehabilitation and follow-up-care) and aims to
      investigate how MBC patients (MBCP) feel about suffering from a "woman's
      disease," what character the stigmatization has, and how it can be prospectively
      reduced. Therefore, a mixed methods design is applied including data of N = 27
      qualitative interviews with MBCP and quantitative data of N = 100 MBCP. Findings
      identify a diverse picture, as stigmatization varies between contexts and
      patients: Most stigmatization concentrates on sexual stigmatization and ignorance
      of MBC and mostly occurs in cancer care systems and work-related contexts. The
      level of stigmatization varies with age and amount of treatment methods received,
      as reported within the created typology of different MBCP stigma types. To
      prospectively reduce stigmatization in MBCP, more publicity of MBC is needed, as
      well as gender-neutral communication and information material.

PMID- 30222031
TI  - Tolerance of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) Inhibitors in
      Patients With Self-Reported Statin Intolerance.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have
      been shown to lower atherogenic lipid markers in patients with statin
      intolerance; however, external validity of these findings is unclear in patients
      with self-reported statin intolerance. OBJECTIVE: The objective of this study was
      to describe the tolerability of evolocumab and alirocumab in patients with self
      reported statin intolerance. Secondary objectives were to describe their efficacy
      and obtainability. METHODS: A retrospective chart review was completed and
      included adult patients with self-reported statin intolerance who were prescribed
      a PCSK9 inhibitor. Patient-reported side effects, laboratory values, and
      insurance information were collected for assessment of study objectives. RESULTS:
      During the study period, 55 patients were prescribed PCSK9 inhibitor, 42 started
      therapy, and 34 had at least 1 follow-up visit. While myalgias occurred in 14.7%
      (n = 5) of patients, flu-like symptoms in 11.8% (n = 4), and fatigue in 2.9% (n =
      1), only 5.9% (n = 2) of prescriptions for PCSK9 inhibitors were discontinued.
      Low-density lipoprotein cholesterol (LDL-C) was reduced 48.7% (95% confidence
      interval [CI]: -1.7%-99.1%), and 20 (58.8%) patients achieved a >=50% reduction
      in LDL-C. Regarding obtainability, of the 57 prescriptions written, 77.2% (n =
      44) required prior authorization and 5.3% (n = 3) were denied by insurance.
      CONCLUSION: PCSK9 inhibitors were well tolerated in patients with self-reported
      statin intolerance.

PMID- 30222030
TI  - Men's Health in Industries: Plastic Plant Pollution and Prevalence of Pre
      diabetes and Type 2 Diabetes Mellitus.
AB  - Plastic production is prominently increasing and its pollution is an emerging
      environmental global health concern. This study aimed to investigate the
      occurrence of pre-diabetes and type 2 diabetes mellitus (T2DM) among nonsmoking
      plastic industry workers. Three hundred and forty volunteers male plastic
      industry workers were interviewed after medical history and examination; finally,
      278 nonsmoking plastic industry workers were selected. The mean age for the
      participants was 38.03 +/- 10.86 years and body mass index was 25.52 +/- 3.15
      (kg/m)2. The plastic industry workers had been exposed to plastic plant pollution
      for 8 hr daily, 6 days in a week. Subjects with glycated hemoglobin (HbA1c) less
      than 5.7% were considered non-diabetics; HbA1c 5.7%-6.4% were pre-diabetics; and
      subjects with HbA1c greater than 6.4% were considered diabetics. In plastic
      industry workers, the prevalence of pre-diabetes was 176 (63.30%) and T2DM was 66
      (23.74%); however, 36 (12.95%) plastic plant workers were normal. The prevalence
      of pre-diabetes and T2DM among plastic industry workers was significantly
      increased with duration of working exposure in plastic industry ( p = .0001).
      Exposure to plastic plant pollution is associated with the prevalence of pre
      diabetes and T2DM among plastic industry workers. The prevalence was associated
      with the duration of working exposure in plastic industry. The occupational and
      environmental health executives must take priority steps to minimize the plastic
      plant pollution from plastic industries to reduce the occurrence of pre-diabetes
      and T2DM among the plastic industrial workers and save the men's health in
      industries.

PMID- 30222032
TI  - Intensive care unit providers more quickly and accurately assess risk of multiple
      harms using an engineered safety display.
AB  - Project Emerge took a systems engineering approach to reduce avoidable harm in
      the intensive care unit. We developed a socio-technology solution to aggregate
      and display information relevant to preventable patient harm. We compared
      providers' efficiency and ability to assess and assimilate data associated with
      patient-safety practice compliance using the existing electronic health record to
      Emerge, and evaluated for speed, accuracy, and the number of mouse clicks
      required. When compared to the standard electronic health record, clinicians were
      faster (529 +/- 210 s vs 1132 +/- 344 s), required fewer mouse clicks (42.3 +/-
      15.3 vs 101.3 +/- 33.9), and were more accurate (24.8 +/- 2.7 of 28 correct vs
      21.2 +/- 2.9 of 28 correct) when using Emerge. All results were statistically
      significant at a p-value < 0.05 using Wilcoxon signed-rank test ( n = 18). Emerge
      has the potential to make clinicians more productive and patients safer by
      reducing the time and errors when obtaining information to reduce preventable
      harm.

PMID- 30222033
TI  - An Examination of the Prescription Renewal Process and Implications for Primary
      Care Physicians and Community Pharmacists.
AB  - In physician practices and pharmacies, staff members work to process prescription
      renewals so that patients receive a steady supply of medications. These functions
      are essential to ensure patients have continuous access to medications and remain
      adherent to prescribed therapies. Despite the incorporation of e-prescribing
      software programs to ease management of these processes, barriers to effective
      management of the prescription renewal process exist. Mismanagement of pharmacy
      adherence programs can ultimately lead to patients receiving inappropriate
      medications and excessive use of staff resources. The objective of this article
      is to examine the prescription renewal process in both the primary care setting
      and the pharmacy and report challenges associated with the process. A literature
      review was conducted to find studies that describe pharmacists' and physicians'
      handlings of prescription renewals, use of e-prescribing software, and benefits
      and barriers to using these technologies. Although studies report e-prescribing
      software improves efficiency in the prescription renewal process, there is a need
      to reduce technological problems that create challenges in use. It is recommended
      that staff within physician practices and pharmacies standardize prescription
      renewal processes and educate patients about the prescription renewal process.

PMID- 30222034
TI  - Data analytics of call log data to identify caller behaviour patterns from a
      mental health and well-being helpline.
AB  - This work presents an analysis of 3.5 million calls made to a mental health and
      well-being helpline, seeking to answer the question, what different groups of
      callers can be characterised by specific usage patterns? Calls were extracted
      from a telephony informatics system. Each call was logged with a date, time,
      duration and a unique identifier allowing for repeat caller analysis. We utilized
      data mining techniques to reveal new insights into help-seeking behaviours.
      Analysis was carried out using unsupervised machine learning (K-means clustering)
      to discover the types of callers, and Fourier transform was used to ascertain
      periodicity in calls. Callers can be clustered into five or six caller groups
      that offer a meaningful interpretation. Cluster groups are stable and re-emerge
      regardless of which year is considered. The volume of calls exhibits strong
      repetitive intra-day and intra-week patterns. Intra-month repetitions are absent.
      This work provides new data-driven findings to model the type and behaviour of
      callers seeking mental health support. It offers insights for computer-mediated
      and telephony-based helpline management.

PMID- 30222035
TI  - Spruce Decline and Diaporthe: Incidence, Taxonomy, Virulence, and Tree
      Susceptibility in Michigan.
AB  - In the early 2000s, spruce trees in Michigan began displaying basal needle drop
      and branch death that slowly progressed upward, symptoms of what we call spruce
      decline. A survey in 2013 revealed that spruce decline was common throughout
      Michigan's Lower Peninsula, and Diaporthe was the most likely pathogen causing
      the cankers associated with these symptoms. Greenhouse inoculation studies
      completed Koch's postulates, confirming that Diaporthe could cause cankers that
      cause needle loss and branch death. The five different Diaporthe haplotypes
      isolated from symptomatic branches during the survey differed in virulence.
      Haplotypes 2, 4, and 5 were more virulent, and differed from each other by only
      one or two base pairs using the internal transcribed spacer (ITS) region and did
      not differ using the beta-tubulin (TUB) gene. These haplotypes were unresolved
      phylogenetically. Haplotypes 1 and 3 were weakly virulent to avirulent on
      multiple spruce taxa, and fell into a resolved Diaporthe eres clade. Spruce taxa
      varied in susceptibility, with Colorado blue spruce (Picea pungens) the most
      susceptible, followed by Norway (P. abies), then white spruce (P. glauca). Spruce
      taxa that were much less susceptible were Black Hills (P. glauca var. densata),
      Serbian (P. omorika), and Meyer spruce (P. meyeri). We demonstrate that one or
      more Diaporthe species is causing cankers on declining spruce in Michigan, and
      these cankers elicit symptoms similar to the branch death expressed by declining
      spruce in the landscape. Future work will focus on further characterizing
      Diaporthe to species, and determining biotic and abiotic stressors that may
      predispose spruce trees to express decline symptoms.

PMID- 30222036
TI  - School Nurses Can Improve the Lives of Students With Myalgic
      Encephalomyelitis/Chronic Fatigue Syndrome.
AB  - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness
      that is defined and diagnosed by its symptoms: extreme fatigue made worse by
      physical and mental activity, pain and decreased mental stamina, among others. A
      long-held, erroneous belief that ME/CFS is not a physiological illness has
      persisted among some clinicians, leading to the denial of a patient's physical
      illness and attributing the symptoms to other causes. The debilitating effects of
      ME/CFS in the pediatric population can affect all aspects of academic, social,
      emotional, and physical development. ME/CFS has been diagnosed in children
      younger than 10 years. Therefore, the school nurse is likely to encounter one or
      more students in the various stages of this disease, putting the school nurse in
      a position to ameliorate the impact of this potentially devastating chronic
      condition.

PMID- 30222037
TI  - From Intention to Action: Nurses as Policy Advocates for Asthma Care in Schools.
AB  - Nurses are familiar with policy at the federal, state, local, and institutional
      levels, but drafting a policy memo might be new to some. School nurses may have
      an interest in writing a health policy memo on their own, with colleagues, as
      part of a nursing organization, or with students who are interested in learning
      about policy development, school health, and safety. The intention of writing a
      policy memo is to offer a concisely written analysis of an issue, including
      background, landscape, and available options, along with recommendations for
      action to persons in authority, such as congressmen, senators, local officials,
      or school boards. The first section of this article serves as an exemplar of a
      policy memo, using the public health topic of asthma. Next, the article focuses
      on barriers to policy development for this condition in schools and offers
      selected strategies to address those barriers. While a discourse concerning
      barriers is not a typical component of a policy memo, this section shows how
      school nurses can draw on evidence to consider the best way to make positive
      change. To construct a sturdy argument for change, school nurses need to
      appreciate potential counterarguments, which is why this exemplar is included.

PMID- 30222038
TI  - Social Resilience and Mental Health Among Eritrean Asylum-Seekers in Switzerland.
AB  - Eritreans comprise the largest group of asylum-seekers in Switzerland. Gaining
      recognized refugee status can take up to 36 months, during which time asylum
      seekers live in a state of legal limbo, intensifying threats to their well-being.
      Resilience and mental health among this population is poorly understood. We
      interviewed 10 asylum-seekers residing in Switzerland using qualitative, in-depth
      interviews. Data were analyzed using the Framework Method. Results indicated that
      mental health was understood as a binary state rather than a continuum and that
      trusted friends and family were responsible for recognizing and attempting to
      treat mental health problems. Pathways to care were potentially interrupted for
      asylum-seekers. Capital building, considered through the lens of social
      resilience, consisted of language learning, establishing of new individual- and
      community-level social networks, and proactive symbolic capital building through
      volunteering. We contextualize the asylum-seekers' experience into a resilience
      framework and offer practical recommendations for improving mental health care
      access.

PMID- 30222039
TI  - Motivation for sport participation and eating disorder risk among female
      collegiate athletes.
AB  - In light of conflicting research regarding eating disorder risk and sports
      participation, the current study examined the relationship between specific
      aspects of sports participation (i.e., level of competition, leanness
      requirements, and physical/cardiovascular intensity level), an individual's
      motivation for sports participation, and eating disorder symptomatology/risk.
      Participants included 319 female collegiate athletes (M age = 19.88; SD = 1.62)
      representing a variety of sports and competition levels. Multilevel modeling
      found that level of competition, receiving a scholarship, age, and years of
      collegiate sport played did not predict eating disorder risk. In the final model,
      there was a significant interaction between intrinsic motivation and sport
      intensity. For high intensity sports, higher levels of intrinsic motivation were
      associated with lower eating disorder risk. For low intensity sports, the level
      of intrinsic motivation did not impact eating disorder risk. For all sport
      intensities, extrinsic motivation was associated with a higher eating disorder
      risk. Results suggest that it is not the specific sport but athletes' motivation
      for those sports with high physical/cardiovascular intensity and leanness
      requirements that is associated with untoward consequences. The results clarify
      conflicting results previously reported in the literature that have primarily
      employed univariate analyses and have implications for athletic development
      programs.

PMID- 30222040
TI  - Congenital and Acquired Systemic Venous Anomalies: A Potpourri of Right to Left
      Shunts.
AB  - Systemic venous anomalies can occur in isolation or in association with other
      congenital heart disease. A left superior vena cava draining to a roofed coronary
      sinus represents the most common venous variant and is usually inconsequential.
      Embryologic or acquired disruptions in systemic veins can be problematic due to
      shunting and/or venous obstruction. In this case series, we report four systemic
      venous anomalies in patients with atrial and ventricular situs solitus. Each case
      demonstrates how clinically significant right to left shunts can occur from a
      systemic vein to the left atrium. Diagnosis in each of these patients was delayed
      due to suboptimal diagnostic testing. Accurate diagnosis can be made by thorough
      anatomic evaluation of the presence, patency, and drainage of all systemic veins
      and supported with proper planning and interpretation of bubble studies.

PMID- 30222042
TI  - Courage and Character, Leaders and Legends: An Interview with Robert Montgomery,
      MD, D.Phil., FACS.

PMID- 30222041
TI  - Insights From Practice With Use of Direct Oral Anticoagulants in Transplantation.
AB  - Solid organ transplant patients are at risk of developing atrial fibrillation and
      venous thromboembolism. Direct oral anticoagulants are considered an attractive
      option for anticoagulation in patients due to their convenience; however, strong
      evidence of their use in transplantation is lacking. We conducted a search using
      Pubmed, Embase, and Scopus databases, in addition to International Society of
      Heart and Lung transplantation and American Transplant Congress abstracts (from
      2012 through December 2017). Fourteen articles were reviewed that included case
      reports, retrospective case series, or chart review analyses of small cohorts.
      Based on this review, the findings can only generate hypotheses that should be
      further studied in a larger randomized cohort. This review can help clinicians
      gain insight into the use of direct oral anticoagulant in this special
      population. For now, clinicians should be cautious about their use in this
      special population.

PMID- 30222043
TI  - Nature Does Not Always Give You a Helping Hand: Comparing the Prosocial Effects
      of Nature at Different Resource and Security Levels.
AB  - Humans become more prosocial after nature exposure. We proposed that the
      prosocial effect pertains to resource (e.g., food, water) and security (e.g.,
      shelter, concealment) features in natural environments. Four studies tested the
      idea that prosociality changes with variations in environmental resource and
      security. Study 1 reported that urban greenspace, a resource feature to urban
      dwellers, predicted more volunteering in low-crime cities, but less so in high
      crime cities. Studies 2 and 3 compared prosociality after exposure to natural
      sceneries in a Resource (high/low) * Security (high/low) design. Participants
      were more prosocial in the high-resource-high-security and low-resource-low
      security conditions. Study 4 compared the four natural environments with two
      control conditions (urban, shape). It reported that not all natural environments
      led to higher prosociality, nor did any of them undermine prosociality. The
      findings supported heterogeneity in nature's prosocial effect. Implications are
      discussed in relation to urban greening and the evolutionary basis of nature's
      effect.

PMID- 30222044
TI  - Unpacking Social Isolation in Men's Suicidality.
AB  - Social isolation has featured as a significant and oftentimes all-encompassing
      risk factor for male suicide, yet, as an explanatory mechanism, it has not been
      unpacked in terms of what it constitutes in everyday life. The current photovoice
      study explores the various dimensions of the lived experience of social
      isolation, as embedded in accounts of suicidality drawn from 35 Canadian men.
      Study participants narrated the following factors as underpinning their social
      isolation: (a) family dysfunction and estrangement, (b) marginality and feeling
      like misfits at school and work, (c) alienation and provisional acceptance of
      health care, (d) ineffectual and self-harming management, (e) intrusive
      dislocating thoughts, and (f) society's burdensome and immoral subjects. These
      interwoven but discrete spheres provide a means for understanding the
      phenomenology of social isolation and a basis for melding ideas about
      connectedness, relationality, personal history, and care, along with strategies
      to support and reduce men's suicidality.

PMID- 30222045
TI  - A Multicenter Qualitative Investigation of the Experiences and Perspectives of
      Substitute Decision Makers Who Underwent Organ Donation Decisions.
AB  - BACKGROUND:: Organ donation research has centered on improving donation rates
      rather than focusing on the experience and impact on substitute decision makers.
      The purpose of this study was to document donor and nondonor family experiences,
      as well as lasting impacts of donation. METHODS:: We used a qualitative
      exploratory design. Semistructured interviews of 27 next-of-kin decision makers
      were conducted, transcribed verbatim, and entered into qualitative software. We
      analyzed the process-based reflections using inductive coding and thematic
      analysis techniques. RESULTS:: Four broad and interrelated themes emerged from
      the data: empathetic care, information needs, donation decision, and impact and
      follow-up. The donation experience left lasting impacts on family members due to
      lingering, unanswered questions. Suggested solutions to improve the donor
      experience for families included providers employing multimodal communication,
      ensuring a proper setting for family meetings, and the presence of a support
      person. DISCUSSION:: We now have improved our understanding of the donation
      process from the perspective of and final impression from the next of kin. To our
      knowledge, this is the largest cohort interviewed in Canada. We have explored
      families' experiences, which included but did not end with donation. We learned
      that despite being appreciative of nurses, physicians, and organ and tissue
      donation coordinators, family members were often troubled by unanswered
      questions. CONCLUSION:: This study described donor and nondonor family
      experiences with donation as well as lasting impacts. Addressing unanswered
      questions should be done in a place sufficiently remote from the donation event
      to enhance the family members' understanding and well-being.

PMID- 30222046
TI  - Implementing MH-TIPS: A Growing Need for Mental Health Services for School-Age
      Children.
AB  - The number of children diagnosed with mental and behavioral health issues is
      increasing each year. Early identification and intervention for these issues are
      vital to improving long-term outcomes. School nurses are among the frontline
      healthcare providers for school-age children, screening and coordinating care for
      multiple physical and mental health conditions. This article describes the
      implementation of a national mental health online training program at a local
      district. Outcomes of the implementation project and implications for school
      nurses are discussed.

PMID- 30222047
TI  - Subjective Memory Problems and Availability of Emotional Support.
AB  - This study examines (1) whether subjective memory problems (SMP) influence
      perceived emotional support from and frequency of contact with family and
      friends; and, (2) the extent to which this relationship is moderated by gender,
      education, and functional limitations. We use the 2014 wave of the Health and
      Retirement Study, a nationally representative panel survey of adults aged 51 and
      over in the United States. While SMP does not affect perceived emotional support
      for younger group (YG; aged 51-64), in older group (OG; aged 65+), SMP is
      associated with reduced perceived support from friends. Also, SMP is predictive
      of fewer writing-based contact with children and friends among OG but not among
      YG. Lastly, we find that the effect of SMP on support from children is contingent
      upon activity of daily living (YG) and gender (OG), while the effect of SMP on
      writing-based contact with both children and friends is contingent upon education
      (YG only).

PMID- 30222048
TI  - Estimates of prediabetes and undiagnosed type 2 diabetes in Denmark: The end of
      an epidemic or a diagnostic artefact?
AB  - BACKGROUND: Up-to-date information on undiagnosed type 2 diabetes and prediabetes
      based on current diagnostic criteria is lacking. The study aimed to model the
      total numbers of people with undiagnosed type 2 diabetes and prediabetes in
      Denmark based on existing population-based surveys. METHODS: Two population-based
      Danish studies with information on HbA1c, date of examination, gender, age and
      known type 2 diabetes were identified: the Danish General Suburban Population
      Study, n = 21,205, and the Danish Health Examination Survey, n = 18,065. The
      prevalence of known, undiagnosed and pre-diabetes were estimated in the Danish
      General Suburban Population Study, and population-level age-specific prevalence
      of known type 2 diabetes was estimated from national registers. The Danish Health
      Examination Survey was included for sensitivity analysis. Combining estimates of
      the survey participation rate among known type 2 diabetes patients with known
      overall participation rates from the studies allowed for the correction of survey
      prevalence to plausible population-level estimates of age- and gender-specific
      prevalence. RESULTS: The prevalence of known, undiagnosed and pre-diabetes was
      highest among men, increasing with age with a peak at age 70. Applying the survey
      based prevalence to the entire Danish population, the estimated number (May 2011)
      with undiagnosed type 2 diabetes was 60,681, corresponding to 24% of all type 2
      diabetes cases, and 292,715 had prediabetes, about 50% more than the total type 2
      diabetes population. CONCLUSIONS: Estimates of undiagnosed type 2 diabetes and
      prediabetes are dramatically lower than reported in previous studies (60,681 vs
      200,000 and 292,715 vs 750,000); however, whether this reflects a true decrease
      in incidence or the change to HbA1c-based diagnostic criteria is not clear.

PMID- 30222049
TI  - A Quality Control Study of the Adherence to Recommended Physiological Targets for
      the Management of Brain-Dead Organ Donors in South Australian Intensive Care
      Units.
AB  - BACKGROUND:: The Australian and New Zealand Intensive Care Society and the
      Australasian Transplant Coordinators Association provide recommendations on the
      physiological management of brain-dead donors. PROBLEM STATEMENT:: How often
      physiological targets are prescribed for brain-dead donors in Australian
      intensive care units (ICUs), and how well these compare to recommended targets is
      unknown. It is also unknown how often recommended targets are achieved,
      irrespective of prescribed targets. METHODS:: We performed a retrospective,
      observational quality control study in 81 adult (>18 years) brain-dead donors to
      describe how often physiological targets were prescribed, comparing these to
      current guidelines. We determined the proportion of observations within the
      recommended target range, irrespective of any prescribed target. We aimed to
      identify poor adherence to recommended targets to guide future quality
      improvement initiatives. OUTCOMES:: Seventy-four (91%) donors had at least 1
      prescribed physiological target written on the ICU chart, with a median of 2
      (range 2-5), and a maximum of 13 targets. Prescribed targets appeared to adhere
      well with recommended targets. Most recommended physiological targets were met
      irrespective of any prescribed target. However, one-quarter of serum sodium
      observations and one-third of blood glucose levels were above the recommended
      target. IMPLICATIONS FOR PRACTICE:: Quality improvement initiatives are required
      to improve the prescription of physiological targets in brain-dead donors in
      South Australia. Serum sodium and serum glucose targets were not met. However,
      this most likely reflects the need for current guidelines to be updated in line
      with current evidence.

PMID- 30222050
TI  - Implementing Cognitive Training Into a Surgical Skill Course: A Pilot Study on
      Laparoscopic Suturing and Knot Tying.
AB  - Mini-invasive surgery-for example, laparoscopy-has challenged surgeons' skills by
      extending their usual haptic space and displaying indirect visual feedback
      through a screen. This may require new mental abilities, including spatial
      orientation and mental representation. This study aimed to test the effect of
      cognitive training based on motor imagery (MI) and action observation (AO) on
      surgical skills. A total of 28 postgraduate residents in surgery took part in our
      study and were randomly distributed into 1 of the 3 following groups: (1) the
      basic surgical skill, which is a short 2-day laparoscopic course + MI + AO group;
      (2) the basic surgical skill group; and (3) the control group. The MI + AO group
      underwent additional cognitive training, whereas the basic surgical skill group
      performed neutral activity during the same time. The laparoscopic suturing and
      knot tying performance as well as spatial ability and mental workload were
      assessed before and after the training period. We did not observe an effect of
      cognitive training on the laparoscopic performance. However, the basic surgical
      skill group significantly improved spatial orientation performance and rated
      lower mental workload, whereas the 2 others exhibited lower performance in a
      mental rotation test. Thus, actual and cognitive training pooled together during
      a short training period elicited too high a strain, thus limiting potential
      improvements. Because MI and AO already showed positive outcomes on surgical
      skills, this issue may, thus, be mitigated according to our specific learning
      conditions. Distributed learning may possibly better divide and share the strain
      associated with new surgical skills learning.

PMID- 30222051
TI  - Lolland-Falster Health Study: Study protocol for a household-based prospective
      cohort study.
AB  - INTRODUCTION: Lolland-Falster consists of two islands in the southern part of
      Denmark where income is lower and life expectancy is shorter than in the general
      Danish population. It is a mixed rural-provincial area with approximately 100,000
      inhabitants. The Lolland-Falster Health Study was initiated to gain knowledge on
      the determinants of health in this disadvantaged area. METHODS: The study is a
      household-based prospective cohort study including people of all ages. The entire
      household of randomly selected inhabitants is allocated either to an invited
      group or to an uninvited, non-contacted control group. The data collection
      encompasses questionnaires, physical examination and biological samples, i.e.
      blood and urine for same-day analysis and biobank storage, and saliva and faeces
      also for biobank storage. The civil registration number links collected data for
      each individual, family and household, with information in Danish registers. The
      data collection started in February 2016 and is estimated to end by 2019 after
      the enrolment of 20,000 people. ANALYSIS: A number of in-depth sub-studies are
      planned. Emphasis will be given to analysis of intra- and inter-family variations
      in health determinants, genetics, lifestyle and health status. Ethics: Region
      Zealand's Ethical Committee on Health Research (SJ-421) and the Danish Data
      Protection Agency (REG-24-2015) approved the study. TRIAL REGISTRATION:
      Clinicaltrials.gov (NCT02482896). Strength and limitations of this study: The
      strength of this study is that Lolland-Falster Health Study is a useful
      scientific resource for investigating cross-sectional difference and time trends
      within and between individuals, families and households. LOFUS adds diversity to
      the previously collected Danish population studies in urbanized areas. The
      limitation is that data collection is expensive. CONCLUSIONS: LOFUS will
      contribute to the knowledge on health in disadvantaged, rural-provincial areas.

PMID- 30222052
TI  - A Locally Adaptive Phase Aberration Correction (LAPAC) Method for Synthetic
      Aperture Sequences.
AB  - Phase aberration is a phenomenon caused by heterogeneity of the speed of sound in
      tissue, in which the actual speed of sound of the tissue is different than the
      assumed speed of sound used for beamforming. It reduces the quality and
      resolution of ultrasonic images and impairs clinical diagnostic capabilities.
      Although phase aberration correction (PAC) methods can reduce these detrimental
      effects, most practical implementations of PAC methods are based on the near
      field phase screen model, which have limited ability to represent the true
      aberration induced by inhomogeneous tissue. Accordingly, we propose a locally
      adaptive phase aberration correction (LAPAC) method that is applied through the
      use of synthetic aperture. The method is tested using full-wave simulations of
      models of human abdominal wall, experiments with tissue aberrators, and in vivo
      carotid images. LAPAC is compared with conventional phase aberration correction
      (cPAC) where aberration profiles are computed at a preselected depth and applied
      to the beamformer's time delays. For all experiments, LAPAC shows an average of 1
      to 2 dB higher contrast than cPAC, and enhancements of 3 to 7 dB with respect to
      the uncorrected cases. We conclude that LAPAC may be a viable option to enhance
      ultrasound image quality images even in the presence of clinically relevant
      aberrating conditions.

PMID- 30222053
TI  - Multifocal Necrotizing Myopathy in Northern Elephant Seal ( Mirounga
      angustirostris) Pups, San Miguel Island, California.
AB  - A field study addressing causes of mortality in freshly dead northern elephant
      seals ( Mirounga angustirostris, Gill, 1866) was conducted on San Miguel Island,
      California, in February 2015. Necropsies were performed on 18 pups ranging in age
      from stillbirths to approximately 7 to 8 weeks. The primary gross diagnoses in
      these pups included trauma, myopathy, starvation/emaciation, infections,
      congenital anomalies, and perinatal mortality. However, 6 (33%) had a previously
      unrecognized myopathy characterized by multiple white streaks that were most
      obvious within the inner layer of the abdominal wall and the small innermost
      ventral intercostal muscles. Following histological examination, 2 more pups from
      San Miguel Island and 6 pups from The Marine Mammal Center (Sausalito,
      California) were found to have similar lesions. Histologically, the lesions
      within the skeletal muscles were characterized by a multifocal polyphasic, mild
      to severe, acute to subacute necrotizing myopathy with mineralization. Acute
      necrosis and degeneration characterized by pyknotic nuclei, eosinophilic
      cytoplasm and cytoplasmic vacuolization were found in smooth muscle myocytes
      within the urinary bladder and digestive system. Degeneration of myocytes was
      present in the tunica media of a few small- to medium-sized vessels and was
      characterized by a vacuolar degeneration and occasionally necrosis. This
      condition has been termed multifocal necrotizing myopathy. A cause of this
      myopathy was not identified.

PMID- 30222054
TI  - Effect of Formulations of Allyl Isothiocyanate on Survival of Macrophomina
      phaseolina from Strawberry.
AB  - Management of Macrophomina phaseolina, causal agent of charcoal rot in many crops
      worldwide, including strawberry, has become more challenging since the phase out
      of methyl bromide (MeBr). The search for a fumigant equally effective as MeBr to
      control soilborne pathogens has been extensive. Allyl isothiocyanate (AITC), a
      biofumigant recently registered in the United States, was evaluated at different
      rates, formulations, fumigant combinations, and application methods in the fall
      of 2014 and 2015 at two research facilities in Balm and Dover, FL. The efficacy
      of treatments was determined by evaluating the survival of M. phaseolina inoculum
      on infested corn-cob litter buried in bags 7.6 and 20.3 cm deep in the center,
      and 7.6 cm deep in the side, of plastic mulched raised beds. The biofumigant was
      shown to be more or as effective in reducing populations of M. phaseolina in the
      soil compared with standard fumigants, such as chloropicrin and 1,3
      dichloropropene with chloropicrin. Thus, AITC is a promising biofumigant
      alternative for managing charcoal rot of strawberry, particularly in organic
      production systems, and should be evaluated for the management of other soilborne
      pathogens.

PMID- 30222055
TI  - Evaluation of Major Ancestors of North American Soybean Cultivars for Resistance
      to Three Pythium Species that Cause Seedling Blight.
AB  - Pythium seedling blight, which can be caused by a number of Pythium spp., is a
      disease that affects soybean (Glycine max) in the United States and Canada.
      Pythium ultimum var. ultimum, one of the most common pathogenic species, is
      favored by cool, wet conditions in early spring and causes seed decay, root rot,
      and seedling damping-off. In all, 102 major ancestors of modern North American
      cultivars and "first progeny" cultivars developed directly from ancestral lines
      were evaluated for resistance to P. ultimum var. ultimum and two other species of
      Pythium in greenhouse assays. Several ancestors and first progeny cultivars, as
      well as the resistant check Archer, had varying levels of partial resistance to
      an Illinois isolate of P. ultimum var. ultimum. In a subsequent experiment, four
      of the most resistant lines (PI 84637, Maple Isle, Fiskeby III, and Fiskeby 840-7
      3) and the susceptible cultivar Kanro were screened for resistance against
      isolates of P. irregulare and P. sylvaticum, and resistance to P. ultimum var.
      ultimum was confirmed. The lines that were partially resistant to P. ultimum var.
      ultimum in the first experiment were also partially resistant to P. irregulare
      and P. sylvaticum. The P. ultimum var. ultimum isolate was the most aggressive of
      the three isolates, followed by the P. irregulare and P. sylvaticum isolates.
      Modern cultivars descended from the soybean lines with partial resistance to
      these pathogens could be useful sources of resistance to Pythium seedling blight
      if they are found to have similar levels of resistance.

PMID- 30222056
TI  - School- and class-level variation in self-harm, suicide ideation and suicide
      attempts in Danish high schools.
AB  - AIM: Strong associations have been found between being exposed to self-harm in
      family and friends and own self-harm in adolescence. Therefore, self-harm and
      suicide behaviour might tend to cluster within school and school classes. The aim
      of this study was to describe the prevalence, frequency and type of self-harm,
      suicide ideation and suicide attempts within Danish high schools and to test
      whether self-harm and suicide behaviour cluster in schools and school classes.
      METHODS: Data came from the Danish National Youth Study 2014, a national survey.
      The respective study included 66,284 high-school students nested in 117 schools
      and 3146 school classes. The prevalence and clustering of self-harm behaviour,
      ever and within the last year, type of self-harm (e.g. cutting, burning,
      scratching and hitting) and suicide ideation and suicide attempts were
      investigated. Multi-level logistic regression was applied to quantify clustering
      among participants within the same class and school. RESULTS: In total, 12,960
      (20%) reported self-harm ever and 5706 (8.6%) within the last year. Prevalence
      was higher among girls than boys. Among girls, cutting (15%) and scratching (13%)
      was the most common type of self-harm, whereas among boys, hitting (6.7%) was
      most prevalent. The degree of clustering of self-harm and suicide behaviour was
      low, with school-level intra-class correlation coefficients (ICC) ranging from
      0.8-1.8% and school class level ICC's from 4.3-6.8%. CONCLUSIONS: This study
      shows that self-harm was common, especially in girls. The degree of clustering of
      self-harm and suicide behaviour in school and school classes was low.

PMID- 30222057
TI  - Pathways into treatment for eating disorders: A quantitative examination of
      treatment barriers and treatment attitudes.
AB  - Most individuals with eating disorders do not receive treatment for their eating
      disorder. Closing this "treatment gap" requires a quantitative examination of
      individuals' attitudes towards accessing various types of treatment and of
      individuals' perceived barriers to seeking treatment. Thus, we recruited a sample
      of 425 individuals with either diagnosed or undiagnosed eating disorders and
      asked them to complete a survey assessing treatment attitudes, treatment
      barriers, and eating disorder symptom severity. Undiagnosed individuals reported
      more positive attitudes towards novel Internet- and smartphone-delivered
      treatments, and stronger barriers relating to eating disorders mental health
      literacy, than diagnosed individuals. Nevertheless, both diagnosed and
      undiagnosed individuals were broadly more positive towards established (i.e., non
      novel) treatments than novel treatments. The strongest barriers to seeking
      treatment were fear of losing control, fear of change, and finding motivation to
      change. Eating disorder symptoms were positively associated with the strength of
      most treatment barriers. Results were broadly unchanged after adjusting for
      individuals' past experiences of treatment. In conclusion, the development and
      dissemination of novel treatments and the provision of eating disorders mental
      health literacy may offer promising potential pathways into treatment for
      individuals with undiagnosed eating disorders. Nevertheless, researchers must pay
      attention to and improve, individuals' attitudes towards accessing these novel
      treatments. The positive correlations of symptom severity with treatment barrier
      strength highlights the importance of early intervention for individuals with
      eating disorders. Finally, the fear of losing control may be a uniquely salient
      treatment barrier for individuals with eating disorders that requires greater
      attention in future research on eating disorder treatment seeking.

PMID- 30222058
TI  - Pap smear accuracy for the diagnosis of cervical precancerous lesions.
AB  - This cross-sectional descriptive study, aimed at accessing the accuracy of Pap
      smear in diagnosing cervical precancerous lesions, was carried out between 3
      January and 30 April 2017. All women screened for cervical dysplasia by means of
      Pap smear with biopsy done for confirmation were subsequently recruited. Data
      were analysed using SPSS 20.0. A total of 231 women were screened for cervical
      dysplasia using Pap smear with 75 biopsies performed. Cervical dysplasia was
      noticed in 54 cases. The sensitivity, specificity, positive predictive and
      negative predictive values of Pap smear were 55.5%, 75%, 88.2% and 33.3%,
      respectively. The sensitivity of Pap smear remains low. Therefore, biopsy should
      be done in cases of macroscopic cervical architectural changes irrespective of
      the result of the Pap smear. Moreover, to reduce the number of women with
      cervical precancerous lesions, the government should make available financial
      resources to set up HPV vaccination programmes rather than screening programmes.

PMID- 30222059
TI  - Family members' experiences and management of resident-to-resident abuse in long
      term residential care.
AB  - OBJECTIVES: Resident-to-resident (RRA) abuse is increasingly recognized as a
      significant problem in long-term residential care.Families have a constant
      presence in this setting, yet their inclusion in research about RRA is minimal.
      The purpose of this study was to examine family members' experiences and
      management of RRA. METHODS: The methodology was critical ethnography.Twelve
      family members participated in in-depth interviews and 56 hours of participant
      observation were conducted. Data were analyzed thematically. RESULTS: The main
      themes illuminate families' experiences of RRA in a context that largely
      normalizes it.In the absence of formal supports, families developed a range of
      management strategies, ranging from passive to active intervention.Organizational
      factors, such as staffing levels and mix, and the physical environment also
      contributed to RRA. DISCUSSION: Families are actively managing RRA in long-term
      residential care. Policies and programs, including educational supports, should
      be developed to validate and support families.

PMID- 30222061
TI  - Good Ole Girls Club.

PMID- 30222060
TI  - Pretreatment 18F-fluorodeoxyglucose Uptake in the Lung Parenchyma Predicts Poor
      Survival After Stereotactic Body Radiation Therapy in Patients With Stage I Non
      Small Cell Lung Cancer.
AB  - PURPOSE: In this study, we aimed to evaluate the prognostic value of
      fluorodeoxyglucose uptake in the lung parenchyma and the presence of subclinical
      interstitial lung disease on computed tomography as predictive factors for
      survival following stereotactic body radiation therapy in patients with stage I
      non-small cell lung cancer. METHODS: We retrospectively evaluated 125 patients
      with stage I non-small cell lung cancer who underwent stereotactic body radiation
      therapy at our institute between December 2005 and March 2013 for various
      demographic and clinical parameters. The fluorodeoxyglucose uptake in the lung
      parenchyma corrected with computed tomography value (tissue fraction-corrected
      standardized uptake value) was quantified using fluorodeoxyglucose-positron
      emission tomography/computed tomography before the therapy. Additionally, the
      radiological findings of interstitial lung disease on computed tomography were
      evaluated. The prognostic analyses were performed using the Kaplan-Meier analysis
      and Cox proportional hazards regression model for univariate and multivariate
      analyses. RESULTS: The median follow-up period was 39 months. The 3-year overall
      survival rate was 67.9%, and the 3-year progression-free survival rate was 52.0%.
      The multivariate analysis indicated that the tissue fraction-corrected
      standardized uptake value was correlated with the patients' overall survival ( P
      = .027, hazard ratio: 2.694, 95% confidence interval: 1.109-8.057). The presence
      of subclinical interstitial lung disease showed no correlation with the overall
      survival ( P = .535, hazard ratio: 1.256, 95% confidence interval: 0.592-2.473).
      CONCLUSION: The results indicated that fluorodeoxyglucose uptake in the lung
      parenchyma, expressed as the tissue fraction-corrected standardized uptake value,
      was an independent prognostic factor in patients with stage I non-small cell lung
      cancer who have received stereotactic body radiation therapy.

PMID- 30222062
TI  - Sarcocystis calchasi Outbreak in Feral Rock Pigeons ( Columba livia) in
      California.
AB  - Twenty-two feral rock pigeons ( Columba livia) from 10 counties in California
      with ataxia, torticollis, and difficulty standing and flying were admitted to
      rehabilitation centers in late winter and spring of 2017 and died or were
      euthanized. Common necropsy findings included thin body condition, generalized
      deep red discoloration of organs, and hemorrhagic subcutaneous neck tissues.
      Meningoencephalitis was observed microscopically in 16 pigeons, and 3 also had
      protozoal schizonts in the brain. The most consistently affected regions of the
      brain were cerebellum and brainstem. Skeletal muscles, and less frequently the
      heart, contained large intrasarcoplasmic bradyzoites typically without
      inflammation. Fifteen of the 22 birds tested positive using pan- Sarcocystis
      polymerase chain reaction. The sequence of the amplicon was most closely related
      to S. calchasi, and the 8 subtyped sequences had 100% homology with S. calchasi.
      This investigation demonstrated the transcontinental and North American spread of
      S. calchasi causing a disease outbreak in free-ranging rock pigeons, thus
      warranting increased surveillance in susceptible native columbids.

PMID- 30222063
TI  - Proliferative Typhlocolitis With Multinucleated Giant Cells: A Nonspecific
      Enteropathy in Immunodeficient Sentinel Mice.
AB  - Beginning in 2015, athymic nude sentinel mice from conventional, medium-, and
      high-security facilities presented to the Comparative Pathology Laboratory (CPL)
      with weight loss, diarrhea, and/or rectal prolapse. Regardless of whether
      clinical signs were present or absent, the gross observation of ceco-colonic
      thickening corresponded histologically to pleocellular typhlocolitis with mucosal
      hyperplasia and lamina proprial multinucleated cells. A subset of affected
      sentinels exhibited granulomatous serositis and hepatosplenic necrosis with
      multinucleated cells. Initial suspicion of mouse hepatitis virus infection was
      excluded by polymerase chain reaction, electron microscopy, and serology.
      Multinucleated giant cells were confirmed as macrophages by positive
      immunoreactivity to Mac-3 and Iba-1 and negative immunoreactivity to
      pancytokeratin. From conventional and medium-security facilities, Helicobacter
      species were identified in 40 of 143 (27.9%) mice, with H. hepaticus accounting
      for 72.5% of identified Helicobacter species. Other agents included opportunistic
      bacterial infection (41/145, 28.3%), murine norovirus (16/106, 15.1%), and
      pinworms (2/146, 1.4%). From high-security facilities, only Enterobacter cloacae
      was identified (2/13, 15.4%), and no evidence of Helicobacter sp., murine
      norovirus, or pinworms was present. No potentially infectious disease agent(s)
      was identified in 71 of 146 (48.6%) affected nude sentinels from conventional and
      medium-security facilities and 11 of 13 (84.6%) affected nude sentinels from high
      security facilities. No statistically significant differences in histologic
      lesion scores were identified between Helicobacter-positive and Helicobacter
      negative mice. Thus, proliferative typhlocolitis with multinucleated giant cells
      was considered a nonspecific histologic pattern associated with a variety of
      primary and opportunistic pathogens in athymic nude mice.

PMID- 30222064
TI  - Cancer survivorship and identity: what about the role of oncology social workers?
AB  - With cancer survival rates rapidly increasing over time, more people are living
      into the survivorship stage of their cancer experience. Furthermore, the
      experience of cancer may impact individuals long after treatment has ceased. This
      paper presents the results of a mapping review implemented to explore key themes
      in the literature related to issues with identity following the completion of
      cancer treatment. The review included 22 studies including quantitative,
      qualitative, mixed method, and review studies as well as conceptual papers.
      Findings revealed key descriptions post-cancer treatment identities, literature
      focused on dominant discourses and counter-discourses around cancer survivorship,
      and key themes focused on identity management and the roles of Oncology Social
      Workers in supporting identity issues in postcancer treatment. This review
      presents a 'map' of current research on identity and cancer survivorship, helping
      to identify major gaps in the literature, direct future research, and inform
      practice.

PMID- 30222065
TI  - Valorization of agro-industrial wastes to produce hydrolytic enzymes by fungal
      solid-state fermentation.
AB  - Nowadays, significant amounts of agro-industrial wastes are discarded by
      industries; however, they represent interesting raw materials for the production
      of high-added value products. In this regard, orange peels (ORA) and exhausted
      sugar beet cossettes (ESBC) have turned out to be promising raw materials for
      hydrolytic enzymes production by solid state fermentation (SSF) and also a source
      of sugars which could be fermented to different high-added value products. The
      maximum activities of xylanase and exo-polygalacturonase (exo-PG) measured in the
      enzymatic extracts obtained after the SSF of ORA were 31,000 U.kg-1 and 17,600
      U.kg-1, respectively; while for ESBC the maximum values reached were 35,000 U.kg
      1 and 28,000 U.kg-1, respectively. The enzymatic extracts obtained in the SSF
      experiments were also employed for the hydrolysis of ORA and ESBC. Furthermore,
      it was found that extracts obtained from SSF of ORA, supplemented with commercial
      cellulase, were more efficient for the hydrolysis of ORA and ESBC than a
      commercial enzyme cocktail typically used for this purpose. In this case, maximum
      reducing sugars concentrations of 57 and 47 g.L-1 were measured after the
      enzymatic hydrolysis of ESBC and ORA, respectively.

PMID- 30222066
TI  - Grindr Killed the Gay Bar, and Other Attempts to Blame Social Technologies for
      Urban Development: A Democratic Approach to Popular Technologies and Queer
      Sociality.
AB  - This article complicates the popular contention that "Grindr is killing the gay
      bar" by using qualitative interviews with Grindr users and a diverse literature
      on urban development. To better understand the factors that have gone into the
      changing face of the gayborhood and the closing of gay bars, this article
      encourages stakeholders to focus on a democratic approach to these technologies
      and considers Grindr and similar apps along with many other factors that affect
      urban development.

PMID- 30222067
TI  - Learning from Excellence: the 'Yaytix' programme.
AB  - Background and aims Learning from error can have a negative impact on the staff
      involved in the error ('second victim phenomenon'1). We created a project, based
      on the principles of the Learning from Excellence project,2 to learn from
      excellence and correct the imbalance of negative to positive feedback in the
      context of hospital practice. Methods and results Using a questionnaire, we
      surveyed staff on existing feedback mechanisms and morale. We then introduced a
      system where staff recorded and commented on examples of excellence in practice.
      Recipients and their supervisors received copies of these reports and the
      feedback was analysed and discussed with senior staff (consultant, senior charge
      nurse, managers). We re-audited the staff two months after starting this project
      and noted improvements in staff morale and in positive reporting. Conclusions
      This project has improved the process of giving and learning from positive
      feedback and had a significant impact on staff morale. We can also demonstrate an
      example of improved clinical practice (from feedback received) and will now
      attempt to measure clinical outcomes with a new prospective study. Finally, we
      hope to set up a regional programme of reporting excellence in South-East
      Scotland.

PMID- 30222068
TI  - Heat stress in rice vermicelli manufacturing factories.
AB  - OBJECTIVE: This study provides an assessment of heat stress in indoor rice
      vermicelli manufacturing factories. METHODS: Worker interviews and heat stress
      assessments were conducted in food manufacturing factories in Singapore. The Wet
      Bulb Globe Temperature (WBGT) and Heat Stress Index (HSI) were used as heat
      stress indicators. RESULTS: The highest WBGT and HSI levels recorded in the rice
      vermicelli manufacturing factories were 36.68 degrees C and 3777 in the drying
      and steaming process respectively. These levels were above the recommended
      permissible HSI and WBGT action limit for heat exposure and considered to be high
      risk. CONCLUSION: Workers in indoor rice vermicelli manufacturing factories can
      be exposed to heat stress, and the current measures in place may not be
      sufficient to protect workers against heat stress injuries. Preventive measures
      such as engineering controls and heat acclimatization programs are important.

PMID- 30222070
TI  - Care coordination in pediatric health care settings: the critical role of social
      work.
AB  - BACKGROUND: Care coordination (CC) is integral to improving health care quality.
      Research on CC by health care social workers (HSWs) in pediatric health care
      settings is limited. This paper aims to operationalize and quantify CC functions
      fulfilled by HSWs in one large urban pediatric hospital. METHODS: Twenty-three
      discrete CC tasks across four categories of assessment, meetings, consultations,
      and facilitation were identified and operationalized by an HSW CC committee
      through a consensus-driven decision-making process. Over three workdays, 22 HSWs
      from 18 unique health care clinic settings recorded total time spent daily on
      each CC activity. RESULTS: Participants spent an average of 78.3% of a typical
      workday on CC activities. Regardless of setting, participants completed tasks
      across all general activity categories of assessment, meetings, consults, and
      facilitation. The most time-consuming CC tasks included biopsychosocial
      assessment, medical team consultations, multidisciplinary care plan facilitation,
      and family meetings. Tasks related to child protection were among the least
      frequently completed. CONCLUSION: CC is a cornerstone of HSW service provision in
      pediatric health care settings. HSWs can be vital collaborators in developing
      innovative transdisciplinary CC models.

PMID- 30222069
TI  - Impact of occupational cadmium exposure on bone in sewage workers.
AB  - Cadmium (Cd) is one of the environmental risk factors for bone loss. The present
      study included 40 sewage workers occupationally exposed to Cd. Forty nonexposed
      men were included as a control group. Current smokers represented 65% and 47.5%
      of the exposed and control groups, respectively. The study aimed to investigate
      the hazard of occupational Cd exposure on bone health. This was achieved through
      measuring serum and urinary Cd, and calcium (Ca), in addition to serum
      osteoprotegerin (OPG) and estrogen receptor-alpha gene. Results showed
      significant elevation in serum Cd, OPG, and urinary Ca levels in the exposed
      compared to the controls. Bony aches and joint pain were more prevalent among the
      exposed workers. Serum and urinary Cd increased in exposed smokers relative to
      control smokers. Also, serum OPG levels showed significant rise among exposed
      smoker and nonsmoker compared to control smoker and nonsmoker groups. Serum Cd
      level increased significantly in PP and pp genotypes in exposed workers compared
      to controls, while elevated levels of serum OPG was observed in PP and Pp
      genotypes in exposed workers relative to controls. Urinary Cd exhibited
      significant rise in both PP and pp genotypes in exposed workers, while Ca
      excretion was elevated in pp genotype only. The study reflected an association of
      genetic predisposition and Cd exposure in progression of osteoporosis. Further
      research is needed to explain the mechanisms of Cd impact on bone. The role of
      smoking is important and hence smoking cessation programs are essential for
      sewage workers.

PMID- 30222071
TI  - In Situ Hybridization for Localization of Ovine Herpesvirus 2, the Agent of Sheep
      Associated Malignant Catarrhal Fever, in Formalin-Fixed Tissues.
AB  - A constraint on understanding the pathogenesis of malignant catarrhal fever (MCF)
      is the limited number of tools to localize infected cells. The amount of
      detectable virus, visualized in the past either by immunohistochemistry or in
      situ hybridization (ISH), has been modest in fixed or frozen tissues. This
      complicates our understanding of the widespread lymphoid proliferation,
      epithelial necrosis/apoptosis, and arteritis-phlebitis that characterize MCF. In
      this work, we developed a probe-based in situ hybridization assay targeting 2
      ovine herpesvirus 2 (OvHV-2) genes, as well as their respective transcripts, in
      formalin-fixed tissues. Using this approach, OvHV-2 nucleic acids were detected
      in lymphocytes in MCF-affected animals following both natural infection (American
      bison and domestic cattle) and experimental infection (American bison, rabbits,
      and pigs). The probe did not cross-react with 4 closely related
      gammaherpesviruses that also cause MCF: alcelaphine herpesvirus 1, alcelaphine
      herpesvirus 2, caprine herpesvirus 2, and ibex-MCF virus (MCFV). No signal was
      detected in control tissues negative for OvHV-2. ISH will be of value in
      analyzing the natural progression of OvHV-2 infection in time-course studies
      following experimental infection and in addressing the pathogenesis of MCF.

PMID- 30222072
TI  - Feasibility of single session high-intensity interval training utilizing speed
      and active recovery to push beyond standard practice post-stroke.
AB  - BACKGROUND: Improvement in overground walking speed reduces dependency and is a
      central focus in post-stroke rehabilitation. Previous studies have shown that
      high-intensity interval training (HIT) can significantly improve functional and
      health-related outcomes in neurologically health individuals more so than
      traditional approaches. Emerging evidence suggests the same may be true post
      stroke. OBJECTIVE: The purpose of this study was to assess the feasibility of a
      single session, novel HIT design. METHODS: Participants walked on a treadmill,
      alternating between one minute at high-intensity and one minute at low-intensity
      for 20 minutes, adjusting the speed of the treadmill to dictate intensity.
      Treadmill speeds were determined from overground self-selected walking speed
      (SSWS). RESULTS: No adverse events occurred during the training sessions. High
      intensity treadmill speeds were significantly faster than treadmill SSWS
      (standard practice; +227%; p < 0.0001) and overground SSWS (+142%; p = 0.003). 15
      of the 21 subjects were able to walk on the treadmill at 150% of overground SSWS;
      with the remaining individuals (n = 6) walking at 123% of overground SSWS.
      Average peak heart rate during HIT was 90% of age-predicted max. CONCLUSIONS:
      These results demonstrate the feasibility of this single session HIT design and
      suggest that individuals following stroke are capable of prolonged training at
      speeds significantly faster than standard practice. Additionally, this training
      intensity elicited heart rate responses in the upper range of vigorous exercise.
      Future studies are needed to investigate a progressive HIT intervention applying
      this design and its effects on functional outcomes as well as cardiovascular
      fitness.

PMID- 30222073
TI  - Seropositivity in animals and risk of occupational brucellosis among abattoirs
      personnel associated with poor work practices and absence of safety policy in
      Egypt.
AB  - Background Occupational hazards are the leading cause of morbidity and mortality
      among abattoirs personnel and animal workers. These hazards result from direct or
      indirect exposure to potential infection and several distressing events during
      routine procedures. Objectives To serologically investigate the potential
      occupational brucellosis hazard at Egyptian abattoirs. To provide an insight on
      the needed biosafety practices that should be implemented to mitigate the spread
      of occupational brucellosis among abattoir workers. Methods Two hundred and
      thirty (n = 230) blood samples were collected from animals in two Egyptian
      abattoirs. The rose Bengal test was used to evaluate the seroprevalence of
      Brucella in abattoir animals. A questionnaire was distributed among abattoir
      personnel to address biosafety gaps and deficiencies as a cause of occupational
      brucellosis. Results The overall seroprevalence of Brucella using the rose Bengal
      test was 75.2% in the two targeted abattoirs. It was obvious that there are gaps
      of malpractices and inconvenient behavior among individuals of the targeted
      community. Conclusions The current findings reveal the missing role of concerned
      authorities and lack of written safety policy. The data highlights the need for
      further research, including isolation and characterization of the causative
      agents, and reliable epidemiological studies.

PMID- 30222074
TI  - Considering the Role of Nativity in the Health and Psychological Wellbeing of
      Black LGBT Adults.
AB  - Recent scholars have underscored how the experiences of LGBT people of color
      cannot be fully understood by considering only the independent contributions of
      race and sexual orientation. Framed by an intersectional lens, the current study
      seeks to address this gap in understanding by considering the role of nativity on
      the health and wellbeing of Black sexual minority adults; we also examined the
      moderating effects of family support and racial community climate on this
      relationship. Using national data from the Social Justice Sexuality Project (N =
      2,166), we discovered that foreign-born Black LGBT adults had similar levels of
      psychological wellbeing and physical health as their native counterparts; family
      support and racial community climate did not moderate this relationship. Our
      findings did, however, substantiate the importance of family and community
      support for all Black LGBT adults, regardless of immigration status. Implications
      of this finding, in addition to directions for future intersectional work on
      racial minority LGBT people, are discussed.

PMID- 30222075
TI  - Structural muscular adaptations in upper limb after stroke: a systematic review.
AB  - BACKGROUND: Stroke is a leading cause of disability in the adult population,
      impairing upper limb (UL) movements affecting activities of daily living. Muscle
      weakness has been associated to disabilities in this population, but much
      attention is given to central nervous system alterations and less to skeletal
      muscles. OBJECTIVE: The objective of this review is to carry out a systematic
      literature review to identify structural muscle alterations in the UL of
      poststroke individuals. METHOD: The search was performed in December, 2017.
      MEDLINE, PubMed, SCOPUS, CINAHL, and Science Direct were used as electronic
      databases. There was no restriction regarding language and publication dates.
      Studies conducted on poststroke subjects and results on UL skeletal muscle
      alterations identified by imaging tests were included. RESULTS: Seven studies
      were included. The sample size and the variables varied among the studies. All
      the studies compared the paretic UL with the nonparetic UL and one of the studies
      also compared healthy subjects. Ultrasonography was the most used measurement
      tool to assess muscle adaptation. CONCLUSIONS: This review demonstrated little
      evidence with poor to fair quality on the structural muscle adaptations in the
      poststroke subjects, showing muscle atrophy, a higher stiffness, and amount of
      fibrous and fat tissue without alterations in lean tissue of distal muscles of
      the paretic UL compared to the nonparetic limb. However, the nonparetic side also
      presented alterations, which makes it an inappropriate comparison. Thus, well
      designed studies addressing this issue are required.

PMID- 30222076
TI  - Gratitude, Social Cognition, and Well-Being in Emerging Adolescents.
AB  - The authors explored Canadian emerging adolescents' social and moral reasoning
      skills (empathy, theory of mind), and their perceptions of gratitude, self
      competencies, and well-being (spiritual, emotional). As part of a larger five
      year longitudinal study, the authors describe results of Year 2 (2016-2017) data
      from 46 ninth-grade students (33 girls; Mage = 13.5 years, SD = 5.436 years) from
      eight schools (Ontario, Canada). Students' perceptions of gratitude,
      spirituality, self-compassion, competencies, and well-being were measured by self
      report questionnaires. Significant positive correlations were found among
      adolescents' perceptions of gratitude, self-competencies, and emotional and
      spiritual well-being. Differently valenced patterns of associations were found
      among students' perceptions of gratitude (appreciation for others and sense of
      abundance), self-compassion, and existential well-being, and spiritual comfort,
      and omnipresence. Simple appreciation was the only aspect of gratitude to show
      significant positive relations with religious well-being. Significant positive
      correlations were found between gratitude (sense of abundance) and self
      compassion, whereas significant negative correlations were found between self
      compassion and empathy, theory of mind, existential well-being, and religious
      well-being. Implications for theory and educational applications are discussed.

PMID- 30222077
TI  - ABCB1 (P-glycoprotein) regulates vitamin D absorption and contributes to its
      transintestinal efflux.
AB  - Efficient intestinal absorption of dietary vitamin D is required in most people
      to ensure an adequate status. Thus, we investigated the involvement of ATP
      binding cassette subfamily B member 1 (ABCB1) in vitamin D intestinal efflux.
      Both cholecalciferol (D3) and 25-hydroxycholecalciferol [25(OH)D3] apical
      effluxes were decreased by chemical inhibition of ABCB1 in Caco-2 cells and
      increased by ABCB1 overexpression in Griptites or Madin-Darby canine kidney type
      II cells. Mice deficient for the 2 murine ABCB1s encoded by Abcb1a and Abcb1b
      genes ( Abcb1-/-) displayed an accumulation of 25(OH)D3 in plasma, intestine,
      brain, liver, and kidneys, together with an increased D3 postprandial response
      after gavage compared with controls. 25(OH)D3 efflux through Abcb1-/- intestinal
      explants was markedly decreased compared with controls. This reduction of
      25(OH)D3 transfer from plasma to lumen was further confirmed in vivo in intestine
      perfused mice. Docking experiments established that both D3 and 25(OH)D3 could
      bind with high affinity to Caenorhabditis elegans P-glycoprotein, used as an
      ABCB1 model. Finally, in a group of 39 healthy male adults, a single-nucleotide
      polymorphism (SNP) in ABCB1 (rs17064) was significantly associated with the
      fasting plasma 25(OH)D3 concentration. Thus, we showed here for the first time
      that ABCB1 is involved in neo-absorbed vitamin D efflux by the enterocytes and
      that it also contributes to vitamin D transintestinal excretion and likely
      impacts vitamin D status.-Margier, M., Collet, X., le May, C., Desmarchelier, C.,
      Andre, F., Lebrun, C., Defoort, C., Bluteau, A., Borel, P., Lespine, A., Reboul,
      E. ABCB1 (P-glycoprotein) regulates vitamin D absorption and contributes to its
      transintestinal efflux.

PMID- 30222079
TI  - CTRP13 inhibits atherosclerosis via autophagy-lysosome-dependent degradation of
      CD36.
AB  - C1q/tumor necrosis factor-related protein 13 (CTRP13) is a secreted adipokine
      that can ameliorate abnormal glucose and lipid metabolism. However, the
      functional role of CTRP13 in the development of atherosclerotic plaques has yet
      to be described. In this study, we collected blood samples from patients of
      coronary artery diseases and apolipoprotein E (ApoE)-/- mice that were fed a
      Western diet for 12 wk to induce atherosclerosis and found that serum CTRP13
      level was decreased. En face staining of aortas and aortic sinus in ApoE-/- mice
      showed that ectopic CTRP13 infusion in vivo dramatically decreased lesion areas,
      as well as reduced inflammatory responses with less macrophage content. In
      primary peritoneal macrophages in vitro, CTRP13 supplement reduced oxidized LDL
      uptake, foam-cell formation, and trapping, together with the suppressed cluster
      of differentiation 36 (CD36) protein levels. Reduced CD36 protein level was
      attributed to the autophagy-lysosome-dependent degradation of CD36 at the post
      transcriptional level. The blocking of autophagy-lysosome induction could
      increase CD36 protein level, foam-cell formation, and migration, thus abolishing
      the protective effects of CTRP13 on atherosclerosis. In summary, these findings
      define CTRP13 as a novel approach for preventing atherosclerotic plaque formation
      via modulation of lipid uptake and foam-cell migration.-Wang, C., Xu, W., Liang,
      M., Huang, D., Huang, K. CTRP13 inhibits atherosclerosis via autophagy-lysosome
      dependent degradation of CD36.

PMID- 30222078
TI  - Tissue-specific regulation of cytochrome c by post-translational modifications:
      respiration, the mitochondrial membrane potential, ROS, and apoptosis.
AB  - Cytochrome c (Cyt c) plays a vital role in the mitochondrial electron transport
      chain (ETC). In addition, it is a key regulator of apoptosis. Cyt c has multiple
      other functions including ROS production and scavenging, cardiolipin
      peroxidation, and mitochondrial protein import. Cyt c is tightly regulated by
      allosteric mechanisms, tissue-specific isoforms, and post-translational
      modifications (PTMs). Distinct residues of Cyt c are modified by PTMs, primarily
      phosphorylations, in a highly tissue-specific manner. These modifications
      downregulate mitochondrial ETC flux and adjust the mitochondrial membrane
      potential (DeltaPsim), to minimize reactive oxygen species (ROS) production under
      normal conditions. In pathologic and acute stress conditions, such as ischemia
      reperfusion, phosphorylations are lost, leading to maximum ETC flux, DeltaPsim
      hyperpolarization, excessive ROS generation, and the release of Cyt c. It is also
      the dephosphorylated form of the protein that leads to maximum caspase
      activation. We discuss the complex regulation of Cyt c and propose that it is a
      central regulatory step of the mammalian ETC that can be rate limiting in normal
      conditions. This regulation is important because it maintains optimal
      intermediate DeltaPsim, limiting ROS generation. We examine the role of Cyt c
      PTMs, including phosphorylation, acetylation, methylation, nitration,
      nitrosylation, and sulfoxidation and consider their potential biological
      significance by evaluating their stoichiometry.-Kalpage, H. A., Bazylianska, V.,
      Recanati, M. A., Fite, A., Liu, J., Wan, J., Mantena, N., Malek, M. H.,
      Podgorski, I., Heath, E. I., Vaishnav, A., Edwards, B. F., Grossman, L. I.,
      Sanderson, T. H., Lee, I., Huttemann, M. Tissue-specific regulation of cytochrome
      c by post-translational modifications: respiration, the mitochondrial membrane
      potential, ROS, and apoptosis.

PMID- 30222080
TI  - Diabetic Foot Fungal Osteomyelitis: No Longer Unknown and Hidden?

PMID- 30222081
TI  - Silver Sulfadiazine and Cerium Nitrate in Ischemic Skin Necrosis of the Leg and
      Foot: Results of a Prospective Randomized Controlled Study.
AB  - Flammacerium is a topical treatment composed of silver sulfadiazine and cerium
      nitrate initially used in burns. The objective was to assess the effectiveness of
      silver sulfadiazine and cerium nitrate on ischemic necrosis wounds of the lower
      limb as an alternative to amputation for a period of 12 weeks. Patients were
      prospectively randomized to receive silver sulfadiazine and cerium nitrate or
      standard care. Patients included adults with an ischemic wound of the lower limb,
      with necrosis covering over at least 50%. Critical ischemia limb was confirmed by
      an ankle-brachial index <0.7 or >1.3 with radiological confirmation. Patient
      demographic data, amputations procedures, wound area, Visual Analogue Scale pain
      rating, clinical infection, and adverse events were recorded. Fifty patients, 34
      males and 16 females, were recruited between January 2010 and April 2014, 25 in
      each group. The mean age was 75.14 years (+/-11.64). Nine amputations (36%)
      occurred in each group. Amputation-free survival was superior in the active
      treatment group versus the standard group (169 393 days, 95% confidence interval
      = 134.926-203.861, vs 169 393 days, 95% confidence interval = 134.926-203.861).
      It was not statistically significant (log-rank, P = .958). Wound area reduction
      between both groups was not statistically different ( P = .651). Less adverse
      events of the lower limb occurred in the active treatment group ( P = .001). Our
      study showed that silver sulfadiazine and cerium nitrate is not inferior to
      standardized care on ischemic necrotic wounds of the lower extremity. Further
      studies are still needed to confirm its effectiveness.

PMID- 30222082
TI  - Horizon Scanning in Lower Extremity Wound Management.

PMID- 30222083
TI  - A dopamine D1 receptor agonist improved learning and memory in morphine-treated
      rats.
AB  - OBJECTIVE: The objective of this article is to study the role of the dopamine
      (DA) D1 receptor in the midbrain periaqueductal grey (PAG) on learning and memory
      in morphine-addicted rats. METHODS: DA D1 receptor agonist SKF81297 and D1
      receptor antagonist SCH SCH23390 were administrated into the PAG, respectively,
      and the learning and memory behavioral changes of morphine addicted rats were
      detected by water maze. Western blot and immunohistochemistry were used to detect
      glutamate decarboxylase 67 (GAD67) and tyrosine receptor kinase B (TrkB) in PAG.
      RESULTS: D1 receptor agonist shortened the latency to platform and increased the
      number of platform crossings, indicating improved learning and memory ability of
      morphine addict rat. D1 receptor agonist increased GAD67 expression and decreased
      TrkB in PAG. CONCLUSION: (1) The PAG is involved in the learning and memory
      changes of the addicted rats; (2) the activation of DA D1 receptor will increase
      the GAD67, reduce the damage to peripheral neurons, and improve the learning and
      memory of the addicted rats; and (3) D1 receptor agonists further reduced TrkB
      expression in morphine-addicted rats, whereas TrkB levels deviated from changes
      in rat behavior.

PMID- 30222084
TI  - Building Specialized Nursing Practice Capacity in Bangladesh: An Educational
      Program to Prepare Nurses to Care for Oncology and Bone Marrow Transplant
      Patients in Dhaka, Bangladesh.
AB  - In 2012, the Minister of Health and other leaders in the Bangladesh government
      approached Massachusetts General Hospital to establish the country's first bone
      marrow transplant program at Dhaka Medical College Hospital to serve the needs of
      the people of Bangladesh. Stated goals of this collaboration included a broad
      focus on the care of oncology patients with a specific emphasis on care of
      patients with hematologic malignancies and of women with gynecologic cancers. The
      purpose of this article is to describe the international nursing collaboration
      between Massachusetts General Hospital, Simmons College, the AK Khan Healthcare
      Trust in Dhaka, and Dhaka Medical College Hospital that was established to share
      nursing knowledge and to build specialized professional nursing capacities to
      deliver high-quality cancer care in the public sector. Over the past 3 years,
      through the educational programs that have been developed within this
      collaboration-the Enhanced Specialized Nurse Training Program-the Bangladeshi
      nurses have received continuing professional development based on Western
      standards of nursing and have been offering nursing care to patients who have
      undergone chemotherapy and bone marrow transplantation. The challenges,
      opportunities, and outcomes of this international collaboration have been highly
      rewarding and mutually beneficial.

PMID- 30222085
TI  - Low to Intermediate Dose Atropine Administration During Dobutamine Stress
      Echocardiography in the Pre-Liver Transplant Population.
AB  - INTRODUCTION:: Dobutamine stress echocardiography (DSE) is frequently used to
      screen for obstructive coronary artery disease in the pre-liver transplant
      evaluation. Although atropine is a commonly used adjunctive medication, no study
      has evaluated its side effect profile in patients with end-stage liver disease
      (ESLD). RESEARCH QUESTION:: What is the safety of atropine in candidates
      undergoing pre-liver transplant evaluation when atropine is used in stress
      testing? DESIGN:: This multicenter, prospective study enrolled patients over a 6
      month period undergoing pre-liver transplant evaluation. Each patient completed a
      questionnaire assessing anticholinergic-related symptoms within 24 hours of
      testing and 48 hours following. Comparisons were made among patients receiving
      any atropine dose versus those who did not and among patients receiving at least
      1 mg atropine and those receiving less/none. RESULTS:: Forty patients were
      evaluated, and 32 (80%) had adjunctive atropine administered. No differences in
      clinical characteristics were noted. In comparisons among patients receiving any
      dose of atropine with those who did not, questionnaire results indicated a higher
      rate of nausea prior to testing and higher overall symptom severity following
      testing in patients not receiving atropine. In comparisons among patients
      receiving less than 1 mg atropine with those receiving at least 1 mg atropine, no
      difference in pre- or posttesting questionnaire responses was present. No patient
      in the study required reversal agents or hospitalization within 7 days of
      testing. CONCLUSIONS:: Atropine, a hepatically metabolized medication, did not
      predispose patients with ESLD to an increased symptom burden, and clinical
      outcomes related to DSE were unaffected.

PMID- 30222086
TI  - Listening to fathers: Personal impacts of raising children with Down syndrome.
AB  - The aim of this qualitative study was to contribute to an understanding of how
      biological fathers ( N = 311) believe having a child with Down syndrome has
      impacted them personally. Thematic analysis was used to derive meaning from
      responses to open-ended survey questions. In addition to describing personal
      impacts, fathers shared how their perspectives shifted over time and possible
      contributory factors. The results indicated that fathers were often deeply
      impacted by the experience of parenting a child with Down syndrome. The vast
      majority expressed positive changes in terms of personal growth; however, it is
      important to note that positive emotions often coexisted with more distressing
      ones such as anxiety and loss. Most fathers reported a positive trajectory in
      terms of their adjustment and many attributed it to learning that their negative
      assumptions about people with Down syndrome were not accurate. Implications for
      practitioners and researchers are discussed.

PMID- 30222087
TI  - Evaluation of the smoking intervention X:IT after the second year: A randomized
      controlled trial.
AB  - AIMS: Review studies on the long-term effects of school-based smoking
      interventions show mixed results. X:IT was a three-year cluster randomized
      controlled trial to prevent uptake of smoking among Danish students from age 13
      years until age 15 years which previously proved effective in preventing smoking
      after the first year of intervention. The aim of this paper was to conduct the
      pre-planned analyses of the effects of the X:IT intervention on smoking after the
      second year. METHODS: We used self-reported questionnaire data from students at
      baseline, first, second, and third follow-up ( n at second follow-up=3269,
      response rate=79.4%). Data from third follow-up were not suitable for analysis.
      OUTCOME MEASURE: 'current smoking', dichotomised into smoke daily, weekly,
      monthly or more seldom versus do not smoke. We performed multilevel, logistic
      regression analyses of available cases and intention-to-treat (ITT) analyses,
      replacing missing outcome values by multiple imputation. RESULTS: The prevalence
      of smoking increased from 5.8% at baseline to 17.0% at second follow-up among
      students at intervention schools, and from 7.6% to 18.7% among students at
      control schools. Analyses of available cases and ITT analyses did not support
      X:IT being effective in preventing smoking after the second year of intervention.
      CONCLUSIONS: Although X:IT was effective after the first year of intervention, we
      were not able to demonstrate any effects after the second year. Implementation of
      the intervention was lower in the second year compared to the first year which
      indicates that the missing effect of the intervention at second follow-up is due
      to lack of implementation.

PMID- 30222088
TI  - Troubling the Teaching and Learning of Gender and Sexuality Diversity in South
      African Education.

PMID- 30222090
TI  - Occupational safety and health regulations and implementation challenges in
      Uganda.
AB  - The burden of occupational diseases and injuries is high in developing countries
      due to several challenges including poor regulatory frameworks. To explore the
      status of occupational safety and health (OSH) policies and related
      implementation challenges in Uganda, we reviewed OSH regulations and conducted
      key informant interviews with stakeholders. We found that the existing OSH laws
      were largely outdated compared to the current needs of workplaces. Challenges
      affecting implementation are related to: gaps in the legal framework, low public
      awareness about OSH, poor planning, and limited human capacity, transparency, and
      accountability. Measures to address these gaps including training, upgrading OSH
      laws and policies, and prioritization are warranted to improve the status of OSH
      in Uganda.

PMID- 30222089
TI  - Vibro-Tactile Enhancement of Speech Intelligibility in Multi-talker Noise for
      Simulated Cochlear Implant Listening.
AB  - Many cochlear implant (CI) users achieve excellent speech understanding in
      acoustically quiet conditions but most perform poorly in the presence of
      background noise. An important contributor to this poor speech-in-noise
      performance is the limited transmission of low-frequency sound information
      through CIs. Recent work has suggested that tactile presentation of this low
      frequency sound information could be used to improve speech-in-noise performance
      for CI users. Building on this work, we investigated whether vibro-tactile
      stimulation can improve speech intelligibility in multi-talker noise. The signal
      used for tactile stimulation was derived from the speech-in-noise using a
      computationally inexpensive algorithm. Eight normal-hearing participants listened
      to CI simulated speech-in-noise both with and without concurrent tactile
      stimulation of their fingertip. Participants' speech recognition performance was
      assessed before and after a training regime, which took place over 3 consecutive
      days and totaled around 30 min of exposure to CI-simulated speech-in-noise with
      concurrent tactile stimulation. Tactile stimulation was found to improve the
      intelligibility of speech in multi-talker noise, and this improvement was found
      to increase in size after training. Presentation of such tactile stimulation
      could be achieved by a compact, portable device and offer an inexpensive and
      noninvasive means for improving speech-in-noise performance in CI users.

PMID- 30222091
TI  - Feline Neovascular Vitreoretinopathy and Anterior Segment Dysgenesis With
      Concurrent Glaucoma in Domestic Cats.
AB  - Feline neovascular vitreoretinopathy (FNV) is a newly recognized rare condition
      affecting kittens and young domestic cats. This study investigated the clinical
      and pathologic findings in 22 cats with FNV. In affected cats, ophthalmoscopy of
      the fundus (when visible) revealed avascular peripheral retinae and epiretinal
      vascular membranes. Frequent nonspecific clinical findings were buphthalmos ( n =
      21), medically uncontrollable glaucoma ( n = 22), and lenticular abnormalities (
      n = 13). Anterior segment dysgenesis (ASD) was detected clinically in affected
      cats ( n = 6). The fellow eye was affected in 11 of 18 cats to a variable degree
      or appeared clinically normal in 7 of 18 cats. The globes were examined
      histologically and using immunohistochemistry for vimentin, glial fibrillary
      acidic protein (GFAP), synaptophysin, neurofilament, laminin, factor VIII-related
      antigen (FVIII-RA), and smooth muscle actin (SMA). Histologically, diagnostic
      features included laminin-positive epiretinal vascular membranes affecting the
      central retina, with an avascular peripheral retina and gliosis. Enucleated
      globes exhibited multiple additional abnormalities, including corneal disease ( n
      = 15), anterior segment dysgenesis ( n = 21), lymphoplasmacytic anterior uveitis
      ( n = 19), peripheral anterior synechiae ( n = 20), retinal degeneration ( n =
      22), and retinal detachment ( n = 19). Gliotic retinae labeled strongly for GFAP
      and vimentin with reduced expression of synaptophysin and neurofilament,
      consistent with degeneration or lack of differentiation. While an avascular
      peripheral retina and epiretinal fibrovascular membranes are also salient
      features of retinopathy of prematurity, there is no evidence to support hyperoxic
      damage in cats with FNV. The cause remains unknown.

PMID- 30222092
TI  - Enlargement of Deinococcus grandis spheroplasts requires  Mg2+ or Ca2.
AB  - While the cell wall strictly controls cell size and morphology in bacteria,
      spheroplasts lack cell walls and can become enlarged in growth medium under
      optimal conditions. Optimal conditions depend on the bacterial species. We
      frequently observed extreme enlargement of spheroplasts of the radiation
      resistant bacterium Deinococcus grandis in Difco Marine Broth 2216, but not in
      TGY broth (a commonly used growth medium for Deinococcus). Thorough investigation
      of media components showed that the presence of Mg2+ or Ca2+ promoted extreme
      spheroplast enlargement, synthesizing the outer membrane. Our findings strongly
      suggest that Mg2+ or Ca2+ enlarges spheroplasts, which could change the lipid
      composition of the spheroplast membrane.

PMID- 30222093
TI  - Ottowia konkukae sp. nov., isolated from rotten biji (tofu residue).
AB  - A Gram-negative, aerobic, non-motile, non-spore-forming and rod-shaped bacterial
      strain, designated SK3863T, was isolated from rotten biji (residue remaining
      after making tofu). This bacterium was characterized in order to determine its
      taxonomic position by using the polyphasic approach. Strain SK3863T grew well at
      25-37  degrees C on Reasoner's 2A agar plates. On the basis of 16S rRNA gene
      sequence similarity, strain SK3863T belonged to the family Comamonadaceae and was
      related to Ottowia beijingensis GCS-AN-3T (96.5 % sequence similarity) and
      Ottowia pentelensis RB3-7T (96.4 %). Lower sequence similarities (96.2 %) were
      found to all of the other recognized members of the genus Ottowia. The G+C
      content of the genomic DNA was 65.8 mol%. The major respiratory lipoquinone was
      ubiquinone 8 and the major fatty acids were C16 : 1omega6c/C16 : 1omega7c, C16 :
      0 and C18 : 1omega7c/C18 : 1omega6c. Strain SK3863T could be differentiated
      genotypically and phenotypically from the recognized species of the genus
      Ottowia. The isolate therefore represents a novel species, for which the name
      Ottowia konkukae sp. nov. is proposed, with the type strain SK3863T (=KCCM
      43236T=DSM 105395T).

PMID- 30222094
TI  - Brumimicrobium salinarum sp. nov., isolated from a marine solar saltern.
AB  - A Gram-stain-negative, aerobic, rod-shaped and orange-coloured strain, designated
      LHR20T, was isolated from a marine solar saltern. The novel strain LHR20T was
      able to grow at 15-40  degrees C (optimum 33-37  degrees C), at pH 6.5-9.5
      (optimum pH 7.5-8.0) and with 2.0-11.0 % (w/v) NaCl (optimum 4.0-5.0 %). MK-6 was
      the sole respiratory quinone, and the major fatty acids were iso-C15 : 0 and iso
      C17 : 0 3-OH. The predominant polar lipids of strain LHR20T were
      phosphatidylethanolamine (PE), aminolipid (AL), glycolipid (GL1) and two
      unidentified lipids (L1, L2). The genomic DNA G+C content was 35.0 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain
      LHR20T was a member of the genus Brumimicrobium and its closest relative was
      Brumimicrobium mesophilum JCM 14063T (97.5 % sequence similarity). The average
      nucleotide identity value between strain LHR20T and B. mesophilum JCM 14063T was
      73.7 %. This evidence from phenotypic, chemotaxonomic and phylogenetic analyses
      suggests that strain LHR20T represents a novel species of the genus
      Brumimicrobium. Therefore, the name Brumimicrobium salinarum sp. nov. is
      proposed. The type strain is LHR20T (=KCTC 62372T=MCCC 1H00247T).

PMID- 30222095
TI  - Maribacter litoralis sp. nov. a marine bacterium isolated from seashore.
AB  - A novel Gram-stain-negative, moderately halophilic and aerobic bacterium,
      designated strain SDRB-Phe2T, was isolated from coastal sediment of the yellow
      sea in Sindu-ri, Republic of Korea. Cells were oxidase-positive, catalase
      positive, rod-shaped and surrounded by a capsule with gliding motility. Colonies
      were yellow-coloured, circular, pulvinate with entire margins. Phylogenetic
      analysis based on 16S rRNA gene sequences showed that strain SDRB-Phe2T formed a
      distinct lineage within the genus Maribacter of the family Flavobacteriaceae.
      Stain SDRB-Phe2T exhibited 16S rRNA gene sequence similarity values of 97.1-98.9
      % to the type strains of Maribacterstanieri, Maribacterspongiicola, Maribacter
      forsetii, Maribacter dokdonensis, Maribacter aquivivus, Maribactercaenipelagi,
      Maribacterlitorisediminis, Maribactersedimenticola, Maribacterulvicola,
      Maribacter confluentis and Maribacter orientalis, and of 94.8-96.7 % to the type
      strains of the other species of the genus Maribacter. Strain SDRB-Phe2T contained
      MK-6 as the predominant respiratory quinone and iso-C15 : 1 G, iso-C15 : 0 and
      summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) as the major fatty acids.
      The polar lipids of strain SDRB-Phe2T were phosphatidylethanolamine, one
      unidentified amino lipid and two unidentified lipids. The DNA G+C content was
      36.2 mol%. DNA-DNA relatedness values of strain SDRB-Phe2T to the type strains of
      the 11 phylogenetically related species of the genus Maribacter were 21.9-38.6 %.
      On the basis of the phenotypic features, phylogenetic and DNA-DNA hybridization
      analyses presented here, strain SDRB-Phe2T (=JCM 32373T=KCTC 62273T=DSM 106042T)
      represents a novel species of the genus Maribacter, for which the name
      Maribacterlitoralis sp. nov. is proposed.

PMID- 30222097
TI  - Chryseolinea flava sp. nov., a new species of Chryseolinea isolated from soil.
AB  - A pale yellow bacterial strain, designated SDU1-6T, was isolated from a soil
      sample collected in the Jinan campus of Shandong University, Shandong Province,
      PR China. The strain was aerobic, motile, Gram-stain-negative and rod-shaped.
      Cellular growth occurred at 13-37  degrees C, pH 5.0-10.0 and with 0-0.1 % (w/v)
      NaCl, and the optimal growth was at 25  degrees C and pH 7.5. SDU1-6T had the
      highest 16S rRNA gene similarity of 95.42 % with Chryseolinea serpens DSM 24574T.
      The genome was 6 542 746 bp in length with 43.5 mol% DNA G+C content. The major
      fatty acids of SDU1-6T were C16 : 1omega5 and iso-C15 : 0, the major menaquinone
      was menaquinone-7 (MK-7) and the major polar lipid was phosphatidylethanolamine.
      On the basis of the polyphasic evidence and the 16S rRNA gene sequence, SDU1-6T
      represents a novel species of the genus Chryseolinea, for which the name
      Chryseolineaflava sp. nov. is proposed. The type strain is SDU1-6T (=CGMCC
      1.13492T=JCM 32520T).

PMID- 30222098
TI  - The monofunctional cobalamin biosynthesis enzyme precorrin-3B synthase (CobZRR)
      is essential for anaerobic photosynthesis in Rhodospirillum rubrum but not for
      aerobic dark metabolism.
AB  - The in vivo physiological role of the gene cobZ, which encodes precorrin-3B
      synthase, which catalyzes the initial porphyrin ring contraction step of
      cobalamin biosynthesis via the cob pathway, has been demonstrated here for the
      first time. Cobalamin is known to be essential for an early step of
      bacteriochlorophyll biosynthesis in anoxygenic purple bacteria. The cobZ (cobZRR)
      gene of the purple bacterium Rhodospirillum rubrum was localized to a 23.5 kb
      insert of chromosomal DNA contained on the cosmid pSC4. pSC4 complemented several
      mutants of bacteriochlorophyll and carotenoid biosynthesis, due to the presence
      of the bchCX and crtCDEF genes at one end of the cosmid insert, flanking cobZRR.
      A second gene, citB/tcuB, immediately downstream of cobZRR, shows homologies to
      both a tricarballylate oxidoreductase (tcuB) and a gene (citB) involved in signal
      transduction during citrate uptake. CobZRR shows extensive homology to the N
      terminal domain of the bifunctional CobZ from Rhodobacter capsulatus, and the R.
      rubrum citB/tcuB gene is homologous to the CobZ C-terminal domain. A mutant,
      SERGK25, containing a terminatorless kanamycin interposon inserted into cobZRR,
      could not grow by anaerobic photosynthesis, but grew normally under dark, aerobic
      and microaerophilic conditions with succinate and fructose as carbon sources. The
      anaerobic in vivo activity of CobZ indicates that it does not require oxygen as a
      substrate. The mutant excreted large amounts of protoporphyrin IX
      monomethylester, a brown precursor of bacteriochlorophyll biosynthesis. The
      mutant was complemented either by the cobZRR gene in trans, or when exogenous
      cobalamin was added to the medium. A deletion mutant of tcuB/citB did not exhibit
      the cob phenotype. Thus, a role for tcuB/citB in cobalamin biosynthesis could not
      be confirmed.

PMID- 30222096
TI  - Pelagivirga sediminicola gen. nov., sp. nov. isolated from the Bohai Sea.
AB  - A Gram-stain-negative bacterium, strain BH-SD19T, that was isolated from a marine
      sediment sample collected from the Bohai Sea, was subjected to a polyphasic
      taxonomic study. Cells of BH-SD19T are non-flagellated, non-gliding, oval-shaped
      rods, 0.5-1.0 um wide and 1.0-2.0 um long. BH-SD19T is strictly aerobic, and
      oxidase- and catalase-positive. Growth occurs at 15-40  degrees C (optimum 35 
      degrees C), at pH 6.0-8.5 (optimum 7.0-7.5) and with 1-10 % (w/v) NaCl (optimum 2
      %). The predominant fatty acids are C19 : 0cyclo omega8c (46.5 %), C16 : 0 (20.3
      %) and C18 : 1omega7c and/or C18 : 1omega6c (10.6 %). The major respiratory
      quinone is Q-10. The major polar lipids are phosphatidylglycerol,
      phosphatidylethanolamine and an unidentified phospholipid. The DNA G+C content is
      64.0 mol%. BH-SD19T shows the highest 16S rRNA sequence similarity to Pontibaca
      methylaminivorans (95.2 %) and strains of species of the genus Roseovarius(93.4
      95.2 %). Sequence similarity values between BH-SD19T and other phylogenetically
      related species are all below 95.0 %. Phylogenetic trees based on 16S rRNA gene
      sequences indicate that BH-SD19T forms a distinct lineage and does not join any
      known genera in the trees. Phenotypic, chemotaxonomic and phylogenetic data
      indicate that BH-SD19T represents a novel genus and species in the family
      Rhodobacteraceae, for which the name Pelagivirga sediminicola gen. nov., sp. nov.
      is proposed. The type strain is BH-SD19T (=CCTCC AB 2017074T=KCTC 62202T).

PMID- 30222099
TI  - Geobacillus yumthangensis sp. nov., a thermophilic bacterium isolated from a
      north-east Indian hot spring.
AB  - A thermophilic, spore-forming, rod-shaped bacterium isolated from the Yumthang
      hot spring in North Sikkim, India was subjected to taxonomic studies. The
      thermophilic bacterial isolate was designated as strain AYN2T. Cells were Gram
      stain-positive, aerobic, motile, rod-shaped, catalase-positive and methyl red
      negative. Strain AYN2T was able to grow in the pH range from 6 to 10 (optimum, pH
      7.5-8.0), at 40-70  degrees C (60  degrees C) and in NaCl concentrations of 0-4 %
      (1 %). The major cellular fatty acids were iso-C15 : 0 (12.8 %), iso-C16 : 0
      (13.9 %) and iso-C17 : 0 (13.8 %). No matches were found in the rtsba6 Sherlock
      libraries. The G+C content of the genomic DNA was 42.11 mol%. Based on
      phylogenetic analysis of the 16S rRNA gene sequences, strain AYNT showed highest
      sequence similarity to the type strain of Geobacillus toebii (96 %). However, the
      phenotypic properties of strain AYN2T were clearly distinct from those of G.
      toebii and related species. On the basis of polyphasic analysis, strain AYN2T
      represents a novel species in the genus Geobacillus, for which the name
      Geobacillus yumthangensis sp. nov. is proposed. The type strain is
      AYN2T(MTCC=12749=KCTC=33950= JCM 32596).

PMID- 30222100
TI  - Nitric oxide controls c-di-GMP turnover in Dinoroseobacter shibae.
AB  - The ubiquitous bacterial second messenger bis-(3'-5')-cyclic dimeric GMP (c-di
      GMP) is involved in the regulation of numerous processes including biofilm
      formation, motility, virulence, cell cycle and differentiation. In this study, we
      searched the genome of the ecologically important marine alphaproteobacterium
      Dinoroseobacter shibae DFL12T for genes encoding putative c-di-GMP-modulating
      enzymes. Overall, D. shibae was found to possess two diguanylate cyclases
      (Dshi_2814 and Dshi_2820) as well as two c-di-GMP-specific phosphodiesterases
      (Dhi_0329 and Dshi_3065). Recombinant expression and purification followed by
      enzymatic analysis revealed that all four proteins exhibit their proposed
      activity. Furthermore, adjacent to Dshi_2814 we identified a gene encoding a heme
      nitric oxide/oxygen binding (H-NOX) protein. These proteins are often found in
      association with c-di-GMP signal transduction pathways and modulate their
      function through binding of diatomic gases such as nitric oxide. Here, we
      demonstrate that H-NOX constitutes a functional unit together with the
      diguanylate cyclase Dshi_2814. NO-bound H-NOX strongly inhibits DGC activity.
      Based on these results, and with respect to previously published data including
      micro-array analysis, we propose an interlinkage of c-di-GMP signalling with cell
      cell communication and differentiation in D. shibae.

PMID- 30222101
TI  - Arthroscopic excision of heterotopic ossification in the rectus femoris muscle
      causing extra-articular anterior hip impingement.
AB  - Subspine impingement is an extra-articular hip impingement syndrome that usually
      occurs when there is abnormal contact between an enlarged or malorientated
      anterior inferior iliac spine (AIIS) and the distal anterior femoral neck in
      straight flexion of the hip. We present the case of a 13-year-old boy with a
      history of left groin pain and loss of range of movement of the hip for over six
      months following an avulsion fracture of the AIIS during a game of rugby. He was
      diagnosed with subspine impingement secondary to a large lesion of heterotopic
      ossification in the rectus femoris; this was dissected and extracted from the
      muscle in toto arthroscopically. This case highlights the importance of
      heterotopic ossification after injury as an important cause for subspine
      impingement in the young adult hip. This is the first report and describes
      subspine impingement secondary to a large lesion of heterotopic ossification.

PMID- 30222102
TI  - Preoperative ultrasound to identify distribution of the lateral femoral cutaneous
      nerve in total hip arthroplasty using the direct anterior approach.
AB  - INTRODUCTION: Recently, the branching pattern of the lateral femoral cutaneous
      nerve (LFCN) named Fan type has been reported that LFCN injury cannot be avoided
      in surgical dissections that use the direct anterior approach to the hip joint in
      the cadaveric study. We hypothesized that the Fan type can be identified by
      ultrasound The aim of this study was to investigate whether LFCN injury occurs in
      DAA-THA in cases identified as the Fan type based on preoperative ultrasound of
      the proximal femur. METHODS: Ultrasonography of the proximal femur on the
      surgical side was performed before surgery and the LFCN distribution was judged
      as the Fan type or Non-Fan type. A self-reported questionnaire was sent to the
      patients at two months after surgery, and the presence or absence of LFCN injury
      was prospectively surveyed. RESULTS: After application of exclusion criteria, 45
      hips were included. LFCN injury was observed after surgery in 9 of the 10
      patients judged as the Fan type based on the ultrasound of the proximal femur
      (positive predictive value: 90%), and no LFCN disorder was actually observed in
      25 of the 26 patients judged as Non-Fan type (specificity: 96.2%). CONCLUSIONS:
      To prevent injury of the LFCN in patients judged as the Fan type on the
      ultrasound test before surgery, the risk of direct injury of the LFCN may be
      reduced through the approach in which an incision is made in the fascia which is
      opposite to the radial spreading, i.e., between the sartorius and tensor fasciae
      latae muscles or slightly medial from it.

PMID- 30222103
TI  - Injury-induced perivascular niche supports alternative differentiation of adult
      rodent CNS progenitor cells.
AB  - Following CNS demyelination, oligodendrocyte progenitor cells (OPCs) are able to
      differentiate into either remyelinating oligodendrocytes (OLs) or remyelinating
      Schwann cells (SCs). However, the signals that determine which type of
      remyelinating cell is generated and the underlying mechanisms involved have not
      been identified. Here, we show that distinctive microenvironments created in
      discrete niches within demyelinated white matter determine fate decisions of
      adult OPCs. By comparative transcriptome profiling we demonstrate that an
      ectopic, injury-induced perivascular niche is enriched with secreted ligands of
      the BMP and Wnt signalling pathways, produced by activated OPCs and endothelium,
      whereas reactive astrocyte within non-vascular area express the dual BMP/Wnt
      antagonist Sostdc1. The balance of BMP/Wnt signalling network is instructive for
      OPCs to undertake fate decision shortly after their activation: disruption of the
      OPCs homeostasis during demyelination results in BMP4 upregulation, which, in the
      absence of Socstdc1, favours SCs differentiation.

PMID- 30222104
TI  - Signaling pathways as linear transmitters.
AB  - One challenge in biology is to make sense of the complexity of biological
      networks. A good system to approach this is signaling pathways, whose well
      characterized molecular details allow us to relate the internal processes of each
      pathway to their input-output behavior. In this study, we analyzed mathematical
      models of three metazoan signaling pathways: the canonical Wnt, MAPK/ERK, and
      Tgfbeta pathways. We find an unexpected convergence: the three pathways behave in
      some physiological contexts as linear signal transmitters. Testing the results
      experimentally, we present direct measurements of linear input-output behavior in
      the Wnt and ERK pathways. Analytics from each model further reveal that linearity
      arises through different means in each pathway, which we tested experimentally in
      the Wnt and ERK pathways. Linearity is a desired property in engineering where it
      facilitates fidelity and superposition in signal transmission. Our findings
      illustrate how cells tune different complex networks to converge on the same
      behavior.

PMID- 30222105
TI  - A novel pH-dependent membrane peptide that binds to EphA2 and inhibits cell
      migration.
AB  - Misregulation of the signaling axis formed by the receptor tyrosine kinase (RTK)
      EphA2 and its ligand, ephrinA1, causes aberrant cell-cell contacts that
      contribute to metastasis. Solid tumors are characterized by an acidic
      extracellular medium. We intend to take advantage of this tumor feature to design
      new molecules that specifically target tumors. We created a novel pH-dependent
      transmembrane peptide, TYPE7, by altering the sequence of the transmembrane
      domain of EphA2. TYPE7 is highly soluble and interacts with the surface of lipid
      membranes at neutral pH, while acidity triggers transmembrane insertion. TYPE7
      binds to endogenous EphA2 and reduces Akt phosphorylation and cell migration as
      effectively as ephrinA1. Interestingly, we found large differences in
      juxtamembrane tyrosine phosphorylation and the extent of EphA2 clustering when
      comparing TYPE7 with activation by ephrinA1. This work shows that it is possible
      to design new pH-triggered membrane peptides to activate RTK and gain insights on
      its activation mechanism.

PMID- 30222106
TI  - Too much of a good thing.
AB  - A mutation that causes heart disease in humans increases the number of active
      myosin heads during muscle contraction in fruit flies, leading to the progressive
      dysfunction of the flight muscles and heart tube.

PMID- 30222108
TI  - Competition for synaptic building blocks shapes synaptic plasticity.
AB  - Changes in the efficacies of synapses are thought to be the neurobiological basis
      of learning and memory. The efficacy of a synapse depends on its current number
      of neurotransmitter receptors. Recent experiments have shown that these receptors
      are highly dynamic, moving back and forth between synapses on time scales of
      seconds and minutes. This suggests spontaneous fluctuations in synaptic
      efficacies and a competition of nearby synapses for available receptors. Here we
      propose a mathematical model of this competition of synapses for neurotransmitter
      receptors from a local dendritic pool. Using minimal assumptions, the model
      produces a fast multiplicative scaling behavior of synapses. Furthermore, the
      model explains a transient form of heterosynaptic plasticity and predicts that
      its amount is inversely related to the size of the local receptor pool. Overall,
      our model reveals logistical tradeoffs during the induction of synaptic
      plasticity due to the rapid exchange of neurotransmitter receptors between
      synapses.

PMID- 30222107
TI  - Conditioning sharpens the spatial representation of rewarded stimuli in mouse
      primary visual cortex.
AB  - Reward is often employed as reinforcement in behavioral paradigms but it is
      unclear how the visuospatial aspect of a stimulus-reward association affects the
      cortical representation of visual space. Using a head-fixed paradigm, we
      conditioned mice to associate the same visual pattern in adjacent retinotopic
      regions with availability and absence of reward. Time-lapse intrinsic optical
      signal imaging under anesthesia showed that conditioning increased the spatial
      separation of mesoscale cortical representations of reward predicting- and non
      reward predicting stimuli. Subsequent in vivo two-photon calcium imaging revealed
      that this improved separation correlated with enhanced population coding for
      retinotopic location, specifically for the trained orientation and spatially
      confined to the V1 region where rewarded and non-rewarded stimulus
      representations bordered. These results are corroborated by conditioning-induced
      differences in the correlation structure of population activity. Thus, the
      cortical representation of visual space is sharpened as consequence of
      associative stimulus-reward learning while the overall retinotopic map remains
      unaltered.

PMID- 30222109
TI  - The microtubule polymerase Stu2 promotes oligomerization of the gamma-TuSC for
      cytoplasmic microtubule nucleation.
AB  - Stu2/XMAP215/ZYG-9/Dis1/Alp14/Msps/ch-TOG family members in association with with
      gamma-tubulin complexes nucleate microtubules, but we know little about the
      interplay of these nucleation factors. Here, we show that the budding yeast Stu2
      in complex with the gamma-tubulin receptor Spc72 nucleates microtubules in vitro
      without the small gamma-tubulin complex (gamma-TuSC). Upon gamma-TuSC addition,
      Stu2 facilitates Spc72-gamma-TuSC interaction by binding to Spc72 and gamma-TuSC.
      Stu2 together with Spc72-gamma-TuSC increases microtubule nucleation in a process
      that is dependent on the TOG domains of Stu2. Importantly, these activities are
      also important for microtubule nucleation in vivo. Stu2 stabilizes Spc72-gamma
      TuSC at the minus end of cytoplasmic microtubules (cMTs) and an in vivo assay
      indicates that cMT nucleation requires the TOG domains of Stu2. Upon gamma
      tubulin depletion, we observed efficient cMT nucleation away from the spindle
      pole body (SPB), which was dependent on Stu2. Thus, gamma-TuSC restricts cMT
      assembly to the SPB whereas Stu2 nucleates cMTs together with gamma-TuSC and
      stabilizes gamma-TuSC at the cMT minus end.

PMID- 30222111
TI  - Therapeutic strategy according to the differing patient response profiles to
      omalizumab in chronic spontaneous urticaria.
AB  - Chronic spontaneous urticaria (CSU) is a heterogeneous condition that can
      severely impact quality of life, which is why rapid disease control is essential.
      Symptomatic first-line treatment of CSU is the licensed dose of second-generation
      H1 antihistamines. For second-line treatment, this dose may be increased by up to
      four times. In patients who fail to respond to these higher doses of H1
      antihistamines, treatment with omalizumab (up to 24 weeks) is recommended to
      achieve disease control. After this 24-week period, the patient response profile
      to omalizumab should be defined in order to identify refractory patients. The
      optimal management approach for refractory patients has not been established. In
      this context, the aim of the present expert consensus study involving a group of
      specialists (allergists and dermatologists) with specific expertise in treating
      urticaria was to define specific patient profiles based on their differing
      responses to omalizumab. Another objective was to develop a treatment algorithm
      based on the specific response profile. First, a comprehensive literature review
      was conducted. Then, a group meeting was held to discuss all issues related to
      the therapeutic management of these patients that had not been addressed in any
      previous studies. In all cases, the experts considered both the available
      evidence and their own clinical experience with omalizumab. We believe that
      implementation of this proposed algorithm will help to optimise the management of
      CSU patients who are refractory to antihistamine treatment, reduce disease
      related costs, and improve QoL.

PMID- 30222110
TI  - Non-rhythmic head-direction cells in the parahippocampal region are not
      constrained by attractor network dynamics.
AB  - Computational models postulate that head-direction (HD) cells are part of an
      attractor network integrating head turns. This network requires inputs from
      visual landmarks to anchor the HD signal to the external world. We investigated
      whether information about HD and visual landmarks is integrated in the medial
      entorhinal cortex and parasubiculum, resulting in neurons expressing a
      conjunctive code for HD and visual landmarks. We found that parahippocampal HD
      cells could be divided into two classes based on their theta-rhythmic activity:
      non-rhythmic and theta-rhythmic HD cells. Manipulations of the visual landmarks
      caused tuning curve alterations in most HD cells, with the largest visually
      driven changes observed in non-rhythmic HD cells. Importantly, the tuning
      modifications of non-rhythmic HD cells were often non-coherent across cells,
      refuting the notion that attractor-like dynamics control non-rhythmic HD cells.
      These findings reveal a new population of non-rhythmic HD cells whose malleable
      organization is controlled by visual landmarks.

PMID- 30222112
TI  - Heterogeneous predisposing factors and etiology in uvula edema patients.
AB  - BACKGROUND AND OBJECTIVE: Edema of the uvula (EU) may appear in isolation or in
      association with other associated clinical manifestations such as urticaria,
      angioedema or anaphylaxis. EU may lead to upper airway obstruction, provoking
      obstructive respiratory distress and asphyxia. Objective: We sought to
      investigate the etiology of, and predisposing factors for, EU in a large
      population of patients referred to an outpatient clinic. METHODS: In this 3-year
      follow-up cohort study, 171 patients presenting with EU were identified and
      classified as having isolated EU or non-isolated EU. The etiology of each
      patient's condition was studied and possible predisposing factors recorded. An
      allergy work-up and a statistical study (bivariate/multivariate analyses) were
      performed. RESULTS: The predisposing factors for both groups of EU patients were
      found to be different. The etiology of the problem was identified for the
      majority of the patients; allergy to Anisakis simplex was the most common cause
      for both groups. Non-steroidal anti-inflammatory drugs and antibiotics were also
      found as etiologies for both groups. CONCLUSIONS: Isolated EU was found to be
      associated with snoring, an elongated uvula and having suffered from previous
      episodes of EU. Associations among groups of EU patients and gender, obesity,
      smoking, alcohol consumption, personal and family atopy or obstructive sleep
      apnea, were not demonstrated. Allergy to A. simplex was the most commonly
      recorded cause.

PMID- 30222113
TI  - Obesity and asthma. Key clinical questions.
AB  - Obesity is an asthma common comorbidity and is associated not only with its
      development, but also with a poorer control and higher severity of it. Recent
      prospective evidence supports the idea that body weight gain precedes the
      development of asthma, but the debate is far from over. The objective of this
      document is to conduct a systematic review of 3 clinical questions related to
      asthma and obesity: 1. Obesity and asthma: the chicken or the egg? Clinical
      insights from epidemiological and phenotypes studies. 2. Is obesity a confounding
      factor in the diagnosis and management of asthma and especially in severe or
      difficult-to-control asthma? 3. How obese asthma subjects respond to
      pharmacological treatments, and to biological drugs? Do we have effective
      specific interventions?. Revised epidemiological, pathological and mechanistic
      evidence combined with data from the intervention clinical trials do not allow us
      to clearly state that obesity is an asthma-causative agent. However, the
      complexity and heterogeneity of these two illnesses make several clinical
      scenarios possible. Furthermore, the diagnosis of asthma in an obese patient
      represents an additional clinical challenge. Physicians need to be aware of the
      confounding effects created by the greater symptomatic perception, the
      alterations of lung function and the different comorbidities that the obese
      subjects present. A exhaustive phenotyping of the obese asthma patient should
      lead us to a rational therapeutic plan, including both, the pharmacological
      approach and anti-obesity specific therapies including a combined plan of diet
      and exercise and in extreme cases, bariatric surgery.

PMID- 30222114
TI  - Neuropathic Pain and Itch Mechanisms Underlying Allergic Conjunctivitis.
AB  - OBJECTIVE: Among the symptom constellation that characterizes allergic
      conjunctivitis, many such as burning and stinging can be attributed to chronic
      neuropathic pain. There is accumulating data to support that these hallmark
      symptoms might be linked to the effects of allergen induced neuromodulation. This
      review will emphasize the key characteristics of neuropathic itch and pain in
      allergic conjunctivitis and its pathologic mechanisms. METHODS: A literature
      review was conducted using a PubMed search focusing on allergic conjunctivitis,
      allergic conjunctivitis, neurogenic inflammation, neuropathic itch, neuropathic
      pain. Articles were reviewed and those discussing clinical course,
      pathophysiology, and neuronal regulation of chronic neuropathic symptoms as
      related to allergic disease were summarized. RESULTS: Recent evidence suggests
      that some symptoms of allergic conjunctivitis may be better represented as a
      chronic neuropathic disorder. We found that neurogenic mechanisms may have a
      significant role in chronic ocular surface inflammation from allergic
      inflammation. Manifestations may be associated with repeated ocular sensory nerve
      injury leading to an acute-to-chronic transition associated with neuropathologic
      changes (peripheral and central sensitization), neuronal dysfunction, and
      spontaneous ocular pain. CONCLUSION: Current management goals of allergic
      conjunctivitis aim to minimize the inflammatory cascade associated with allergic
      response in the initial stages of the pathological mechanism. Based on the
      mechanistic data reviewed herein, the recognition that neuronal inflammation
      explains many of the symptoms in allergic conjunctivitis opens new frontiers for
      drug discovery.

PMID- 30222115
TI  - Quality standards for allergen immunotherapy clinics in Spain. Consensus
      document.
AB  - BACKGROUND AND OBJECTIVE: The allergen immunotherapy clinics (AITC) in Spain are
      very different in terms of structure, organisation, resources and portfolio of
      services. Therefore, it is essential to unify treatment criteria and define
      quality standards for the most complex AITCs. Objective: To establish a series of
      recommendations that will make it possible to guarantee quality and safety in the
      administration of immunotherapy and to define the quality standards for the most
      complex AITCs. METHODS: : This project began with an online survey of 65 allergy
      departments or units all over Spain conducted in 2013. Next, a two-phase
      consensus process was carried out. In the first, ten experts defined and agreed
      on the standards using the RAND/UCLA Appropriateness method; in the second, the
      agreements were validated by means of a Delphi consultation in two rounds to 84
      experts. RESULTS: Consensus was reached on minimum safety and quality criteria in
      the administration of allergen immunotherapy (AIT), and two levels of highly
      complex AITCs were defined: accredited AITCs (AITCA) and AITCs accredited with
      excellence (AITCAE). Consensus was also reached on quality standards and
      accreditation criteria for both levels. CONCLUSIONS: This project is pioneering
      in terms of its purpose - the definition of quality standards for AITCs - and for
      the use of structured participation techniques - a combination of the RAND/UCLA
      and Delphi methods. The results, together with some minimum standards for quality
      and safety in administering AIT, is a set of quality criteria for AITC
      accreditation supported by a broad panel of SEAIC experts.

PMID- 30222116
TI  - Intravascular ultrasound findings of the Fantom sirolimus-eluting bioresorbable
      scaffold at six- and nine-month follow-up: the FANTOM II study.
AB  - AIMS: FANTOM II is a prospective multicentre trial assessing the safety and
      efficacy of the Fantom sirolimus-eluting bioresorbable coronary scaffold (BRS).
      The present substudy focuses on the six- and nine-month IVUS findings. METHODS
      AND RESULTS: A total of 240 patients with de novo coronary artery lesions
      presenting with stable or unstable disease were included in two sequential
      cohorts (cohort A [n=117] and cohort B [n=123]) in which angiographic follow-up
      was performed at either six or nine months, respectively. Matched IVUS data were
      available for 35 paired cases in cohort A and 26 paired cases in cohort B. At six
      months, mean and minimum scaffold area (SA) decreased from 6.09+/-1.08 mm2 to
      5.88+/-1.07 mm2, p=0.009, and 5.27+/-0.99 mm2 to 5.05+/-0.99 mm2, p=0.01,
      respectively. At nine months, no significant change in mean scaffold and minimum
      scaffold area was observed (6.46+/-1.11 mm2 to 6.38+/-0.96 mm2; p=0.35, and
      5.45+/-1.00 mm2 to 5.36+/-0.86 mm2; p=0.32, respectively). Neointimal hyperplasia
      area was low at both six (0.11+/-0.12 mm2) and nine months (0.20+/-0.21 mm2), as
      was in-scaffold obstruction volume (1.94+/-2.25% at six months, and 3.40+/-4.11%
      at nine months). CONCLUSIONS: The use of the Fantom BRS in stable coronary artery
      disease was associated with low rates of neointimal hyperplasia volume and in
      scaffold volume obstruction at both six and nine months.

PMID- 30222117
TI  - First-in-man use of the new-generation TriGUARD 3 cerebral embolic protection
      device during transcatheter aortic valve implantation.

PMID- 30222118
TI  - Long-term follow-up of spontaneous coronary artery dissection treated with
      bioresorbable scaffolds.

PMID- 30222119
TI  - Prevalence of neoatherosclerosis in sirolimus-eluting stents in a very late phase
      after implantation.
AB  - AIMS: We sought to investigate subclinical neoatherosclerotic changes and the
      healing response to sirolimus-eluting stents (SESs) to clarify the clinical
      safety and the neointimal pathology of SESs more than 10 years after
      implantation. METHODS AND RESULTS: We investigated a total of 180 SESs without
      stent failure in 103 patients who underwent optical coherence tomography (OCT)
      examination of stented vessels more than 5 years after implantation. We assessed
      the presence or absence of neoatherosclerosis and the healing process by OCT and
      compared the results between stents at 5 to 10 years after implantation (Group A,
      114 stents with 19,873 struts) and stents more than 10 years after implantation
      (Group B, 66 stents with 10,937 struts). The median stent age of the whole cohort
      was 9.4 (7.8-10.9) years. In the OCT analysis, Group B was associated with higher
      frequencies of neoatherosclerosis than Group A. However, the prevalence of
      uncovered stents and stent malapposition was not significantly different between
      the two groups. CONCLUSIONS: SESs of more than 10 years of age are associated
      with a higher frequency of OCT-defined neoatherosclerosis than SESs of 5 to 10
      years of age, indicating continuous development of neoatherosclerosis beyond 10
      years after implantation.

PMID- 30222120
TI  - Randomised comparison of a biodegradable polymer ultra-thin sirolimus-eluting
      stent versus a durable polymer everolimus-eluting stent in patients with de novo
      native coronary artery lesions: the meriT-V trial.
AB  - AIMS: The aim of this study was to evaluate the safety and efficacy of the
      BioMime sirolimus-eluting coronary stent (SES) compared to the XIENCE family of
      everolimus-eluting coronary stents (EES) in the treatment of patients with de
      novo native coronary artery lesions. METHODS AND RESULTS: The meriT-V is a
      prospective, multicentre, randomised, open-label, active-controlled, non
      inferiority trial. A total of 256 patients with up to two de novo native coronary
      artery lesions were enrolled and randomly assigned (2:1) to BioMime SES or XIENCE
      EES. BioMime SES was non-inferior to XIENCE EES for the primary endpoint of in
      stent late lumen loss (0.15+/-0.27 mm vs. 0.15+/-0.29 mm; difference: -0.006 mm;
      95% confidence interval: -0.085 to 0.072; p=0.87; p for non-inferiority <0.0001)
      at nine-month follow-up. The major adverse cardiac events rate was numerically
      lower in the BioMime SES group (2.98% vs. 7.14%; p=0.13), driven by a
      statistically significant lower risk of any myocardial infarction (0.60% vs.
      4.76%; p=0.03), when compared with the XIENCE EES group. There was no difference
      in target vessel myocardial infarction (p=0.62) between the groups. There was no
      definite or probable stent thrombosis in either group. CONCLUSIONS: In the
      treatment of de novo native coronary artery lesions, the biodegradable polymer
      ultra-thin SES (BioMime) was non-inferior to a durable polymer EES (XIENCE) at
      nine-month follow-up. Further studies powered for clinical endpoints are needed.

PMID- 30222121
TI  - The fate of spontaneous coronary artery dissection: insight from intravascular
      imaging at a late follow-up.

PMID- 30222122
TI  - Real-world experience of the left distal transradial approach for coronary
      angiography and percutaneous coronary intervention: a prospective observational
      study (LeDRA).
AB  - AIMS: This study aimed to evaluate the feasibility and safety of the left distal
      transradial approach (ldTRA) as a default route for coronary angiography (CAG)
      and percutaneous coronary intervention (PCI). METHODS AND RESULTS: Between
      October 2017 and January 2018, 200 consecutive patients were enrolled in a single
      centre. The left distal radial artery was punctured with a 20-gauge venipuncture
      catheter needle by three expert left radial approach operators. The success rates
      of arterial puncture, CAG, and PCI were 95.5% (191/200), 100% (187/187), and
      98.9% (86/87), respectively. Four patients scheduled for staged PCI skipped the
      routine diagnostic CAG. Puncture time and fluoroscopic time were 3.0+/-2.8
      minutes and 11.3+/-18.4 minutes, respectively. Haemostasis time was 151.8+/-39.9
      minutes. A total of 15 (7.9%) puncture site complications occurred, including 14
      (7.4%) minor haematomas and one (0.5%) arterial dissection, in which the artery
      was patent at one-month follow-up. Two patients complained of left thumb numbness
      at one-month follow-up. No distal radial artery occlusion, perforation,
      pseudoaneurysm, or arteriovenous fistula occurred. CONCLUSIONS: The success and
      complication rates of ldTRA support the feasibility and safety of this procedure.
      Larger randomised comparison studies are needed to support this preliminary
      evidence.

PMID- 30222123
TI  - Safety and performance of diagnostic electrical mapping of renal nerves in
      hypertensive patients.
AB  - AIMS: To evaluate the safety and performance of renal nerve stimulation (RNS) for
      diagnostic mapping of the renal nerves. METHODS AND RESULTS: In this first-in-man
      study, twenty hypertensive patients underwent RNS using the ConfidenHTTM system.
      Bilateral stimulations were performed at 3 to 4 sites per artery at 2 and 4 mA.
      The primary endpoint was change in systolic blood pressure (SBP). Mean office
      blood pressure was 156/89 mmHg. No peri-procedural adverse events occurred.
      Stimulation with 2 mA resulted in a maximum change of 8.3 +/- 6.3 mmHg in SBP
      (based on 119 stimulations; p <0.001), while stimulating with 4 mA resulted in a
      maximum change of 10.1 +/- 7.8 mmHg (based on 61 stimulations; p<0.001). The mean
      change in SBP did not vary between mid, distal or branch sites when stimulating
      at 2mA but was significantly higher at ostial (23 +/- 14 mmHg) than in non-ostial
      locations (9 +/- 7 mmHg) when stimulating at 4 mA (p=0.003). CONCLUSIONS: RNS can
      be performed safe and effective along the renal artery and results in a large
      variation in temporary BP changes per patient and per anatomic location. RNS
      might help in optimizing treatment effect and selecting potential responders to
      renal sympathetic denervation.

PMID- 30222124
TI  - Double balloon catheters: a promising tool for induction of labor in multiparous
      women with unfavourable cervices.
AB  - OBJECTIVE: The aim of the present study is to compare the effectiveness and
      safety of oxytocin and cervical ripening balloon in women with unfavorable
      cervices for inducing labor. MATERIAL AND METHODS: Total of eighty pregnant women
      between 37-41 gestational weeks having singleton pregnancies and intact membranes
      with unfavorable cervix were randomized in two groups, cervical ripening balloon
      (n=40) and oxytocin infusion (n=40). The primary outcomes were the labor time and
      the route of delivery. Secondary outcomes were the effect of parity on time of
      labor, obstetric and perinatal outcomes. RESULTS: The median time to delivery was
      9,45 hours in cervical ripening balloon and 13,2 hours in oxytocin group in
      multiparous women. The differences were statistically significant (p<0.001).
      Median time until delivery was 11.48 hours at cervical ripening balloon group and
      13,46 hours at oxytocin group; the differences were statistically significant
      (p<0.001). Cesarean delivery ratios were similar in both groups (p=0.431).
      CONCLUSION: The results of the present study were promising for balloon usage
      especially in multiparous women. It is beneficial to support these data with wide
      ranged population based studies.

PMID- 30222125
TI  - The relationship between semen parameters in processed and unprocessed semen with
      IUI success rate.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between Semen
      Parameters and IUI success rate. MATERIAL AND METHODS: This retrospective study
      was carried out during a 4 year period (2011-2015) on the medical records of 350
      couples admitted at the infertility center of Beast Hospital in Tehran. The
      participants' data such as age, duration of infertility, semen parameters
      (including volume, concentration, motility, normal morphology and TMSC) before
      and after sperm processing as well as the IUI results were extracted from the
      patients' records. Only the first IUI cycle of the couples was considered. The
      main outcome criterion for the IUI success was serum positive beta-hCG 14 days
      after IUI. The collected data were analyzed with Mann-Whitney, Chi-Square and
      Fisher's exact tests. RESULTS: The overall pregnancy rate for each couple was
      reported as 23.42% (82/350). There was no significant difference in the mean age
      of the couple and infertility duration between the groups who achieved pregnancy
      and those who failed. The two groups did not show any significant difference in
      pre and post processing of semen parameters (including volume, concentration and
      TMSC). Sperm motility and normal sperm morphology before and after sperm
      processing were significantly different between the two groups, respectively (
      p=.023 before sperm processing and p= .032 after ) ( p=.032 before sperm
      processing and p= .007 after). CONCLUSION: Sperm motility and normal sperm
      morphology have effect in IUI success.

PMID- 30222126
TI  - Diverging beam with synthetic aperture technique for rotation elastography:
      preliminary experimental results.
AB  - Rotation Elastogram (RE) is a 2D spatial distribution map of the estimated local
      rigid-body rotation undergone by a target when subjected to an external
      compression, which is one of the recent variants in elastographic imaging. A
      recent study has shown that inclusion-contrast in RE is independent of inclusion
      background modulus contrast and thus may be helpful in distinguishing between
      barely-stiff benign and malignant lesions. However, estimation of quality RE
      requires not only precise axial displacement estimates but also lateral
      displacement estimates. The widely used conventional focused beamforming
      technique using linear array (CFB-LA) provides better lateral resolution only
      over the depth of focus, which still results in poorer quality lateral
      displacement estimates compared to the axial displacement estimates. As an
      alternative to overcome this depth-dependent lateral resolution and obtain an
      improved lateral resolution, synthetic aperture-based approaches have been
      proposed in literature. Recently, we developed a synthetic aperture-based method,
      diverging beam with synthetic aperture technique (DB-SAT) that was aimed to not
      only reduce the ultrasound system complexity, but also provide improved lateral
      resolution throughout the depth of imaging and at higher frame-rate than that is
      possible in CFB-LA. In this paper, we report the preliminary experimental
      findings on the use of DB-SAT on RE and compare the resultant image quality
      against that obtained using often-employed CFB-LA and the synthetic transmit
      aperture (STA) technique. The investigation was done on tissue-mimicking phantoms
      and using contrast-to-noise ratio (CNR) as the metric for performance evaluation.
      The estimated CNR values from the REs obtained using CFB-LA, STA, and DB-SAT were
      2.69  +/-  0.81, 1.35  +/-  0.22, and 14.71  +/-  9.83, respectively, for
      inclusion present at 55 mm depth. The obtained results clearly demonstrated that
      the quality of RE can be improved significantly, especially at larger depth,
      using DB-SAT compared to that obtained using CFB-LA and STA technique.

PMID- 30222127
TI  - In vivo simultaneous imaging with 99mTc and 18F using a Compton camera.
AB  - We have been developing a medical imaging technique using a Compton camera. This
      study evaluates the feasibility of clear imaging with 99mTc and 18F
      simultaneously, and demonstrates in vivo imaging with 99mTc and/or 18F. We used a
      Compton camera with silicon and cadmium telluride (Si/CdTe) semiconductors. We
      estimated the imaging performance of the Compton camera for 141 keV and 511 keV
      gamma rays from 99mTc and 22Na, respectively. Next, we simultaneously imaged
      99mTc and 18F point sources to evaluate the cross-talk artifacts produced by a
      higher energy gamma-ray background. Then, in the in vivo experiments, three rats
      were injected with 99mTc-dimercaptosuccinic acid and/or 18F-fluorodeoxyglucose
      and imaged. The Compton images were compared with PET images. The rats were
      euthanized, and the activities in their organs were measured using a well
      counter. The energy resolution and spatial resolution were measured for the
      sources. No apparent cross-talk artifacts were observed in the practical-activity
      ratio (99mTc:18F  =  1:16). We succeeded in imaging the distributions of 99mTc
      and 18F simultaneously, and the results were consistent with the PET images and
      well counter measurements. Our Si/CdTe Compton camera can thus work as a multi
      tracer imager, covering various SPECT and PET probes, with less cross-talk
      artifacts in comparison to the conventional Anger cameras using a collimator. Our
      findings suggest the possibility of human trials.

PMID- 30222128
TI  - Heisenberg Ising-Kondo necklace model with transverse field for the heavy fermion
      compound URu2Si2.
AB  - In this work, we introduce the Heisenberg Ising-Kondo necklace with transverse
      field as a possible model to describe the heavy-fermion compound URu2Si2. The
      physics of this compound presents many open questions, like the transition to the
      hidden order (HO) phase at T 0  =  17.5 K. Our Hamiltonian includes elements that
      come from crystal field processes and Ruderman-Kittel-Kasuya-Yosida (RKKY)
      interaction. The main idea is to allow the transverse field, that a priori acts
      only in the localized moments, to influence the conduction-electrons via the RKKY
      interaction. Our results, obtained using a spin-wave approach for a one
      dimensional lattice system, reveal a re-entrance behavior on the zero temperature
      phase diagram. This is an interesting result since combined with the
      magnetization values of the canted AF phase allow to link this phase with the
      mixed hidden order/large moment antiferromagnetic (HO/LMAF) phase observed in
      URu2Si2.

PMID- 30222129
TI  - Band gap engineering of a MoS2 monolayer through oxygen alloying: an ab initio
      study.
AB  - Oxygen (O) alloying in a MoS2 monolayer appearing in different shapes: line
      ordered, cluster and random have been theoretically designed, for band gap
      engineering in order to extend its nanotechnological applications. The
      thermodynamic stability, structural and electronic properties of these alloy
      configurations at each concentration have been comparatively studied using the
      density functional theory methods. Based on the formation energy analysis, the O
      line-ordered alloys are most stable compared to the well known random and cluster
      alloys at high concentration, while at low concentration they compete. The
      lattice constants of all the alloyed systems decrease linearly with the increase
      in O concentration, consistent with Vegard's law. The Mo-O bond lengths are
      shorter than Mo-S leading to a reduction in the band gap, based on density of
      state analysis. The partial charge density reconciling with the partial density
      of states analysis reveals that the band gap reduction is mainly contributed by
      the Mo 4d and O 2p orbitals as shown at the band edges of the density of states
      plots. Creation of stacking of MoS2 with MoO2 gives metallic character, with Mo
      4d orbital crossing the Fermi level. The O alloys in a MoS2 monolayer should be
      considered to be an effective way to engineer the band gap for designing new
      nanoelectronic devices with novel performance.

PMID- 30222130
TI  - Reverse-engineering of graphene on metal surfaces: a case study of embedded
      ruthenium.
AB  - Using scanning tunneling microscopy, x-ray photoelectron spectroscopy, and x-ray
      absorption spectroscopy, we show that Ru forms metallic nanoislands on graphite,
      covered by a graphene monolayer. These islands are air-stable, contain 2-4 layers
      of Ru, and have diameters on the order of 10 nm. To produce these nanoislands two
      conditions must be met during synthesis. The graphite surface must be ion
      bombarded, and subsequently held at an elevated temperature (1000-1180 K) during
      Ru deposition. A coincidence lattice forms between the graphene overlayer and the
      Ru island top. Its characteristics-coincidence lattice constant, corrugation
      amplitude, and variation of carbon lattice appearance within the unit cell
      closely resemble the well-established characteristics of single-layer graphene on
      the (0001) surface of bulk Ru. Quantitative analysis of the graphene lattice in
      relation to the coincidence lattice on the island tops show that the two
      dimensional lattice constant of the underlying metal equals that of bulk
      Ru(0001), within experimental error. The embedded Ru islands are energetically
      favored over on-top (adsorbed) islands, based on density-functional-theory
      calculations for Ru films with 1-3 Ru layers. We propose a formation mechanism in
      which Ru atoms intercalate via defects that act as entry portals to the carbon
      galleries, followed by nucleation and growth in the galleries. In this model,
      high deposition temperature is necessary to prevent blockage of entry portals.

PMID- 30222131
TI  - A phenomenological approach to the deposition pattern of evaporating droplets
      with contact line pinning.
AB  - When an evaporating droplet of colloidal suspension dries on a solid surface with
      the contact line pinned, the solute particles are driven by the solvent flow
      toward the edge and form a ring-like deposition pattern. In this work, we take
      into account the contact angle hysteresis and incorporate it into the effective
      model of Man and Doi (2016 Phys. Rev. Lett. 116 066101) which is based on
      Onsager's variational principle. We show that single-ring pattern is formed when
      the contact line pinning and/or friction are sufficiently strong. We demonstrate
      that there exists an appropriate range for contact line pinning and friction in
      which two rings can be formed in the deposition pattern, one at the initially
      pinned contact line and the other a bit closer to the center of droplet.

PMID- 30222132
TI  - Ineffectiveness of the Dzyaloshinskii-Moriya interaction in the dynamical quantum
      phase transition in the ITF model.
AB  - Quantum phase transition occurs at a quantum critical value of a control
      parameter such as the magnetic field in the Ising model in a transverse magnetic
      field (ITF). Recently, it is shown that ramping across the quantum critical point
      generates non-analytic behaviors in the time evolution of a closed quantum system
      in the thermodynamic limit at zero temperature. The mentioned phenomenon is
      called the dynamical quantum phase transition (DQPT). Here, we consider the one
      dimensional ITF model with added the Dzyaloshinskii-Moriya interaction (DMI).
      Using the fermionization technique, the Hamiltonian is exactly diagonalized.
      Although the DMI induces chiral phase in the ground state phase diagram of the
      model, the study of the rate function of the return probability has proven that
      the DMI does not affect the DQPT. We conclude accordingly that the ramping across
      the quantum critical point is not a necessary and sufficient condition for DQPT.

PMID- 30222133
TI  - Water entry and fall of hydrophobic and superhydrophobic Teflon spheres.
AB  - Hydrophobic and superhydrophobic solid Teflon spheres have been observed while
      settling in water under the action of gravity, starting from different initial
      conditions, and have been followed until the steady-state is reached. The
      superhydrophobic sphere features a nano/microtextured surface and advancing and
      receding water contact angles equal to, respectively, [Formula: see text] and
      [Formula: see text]. When impacting water from air, both spheres can entrap a
      conspicuous amount of air deriving from the sealing of a macro-sized air cavity
      formed upon impact (air cavity trapping) and standing at the rear part of the
      settling sphere. It is shown that this air amount, like a spindle, reduces the
      force coefficient exerted on the sphere, basically acting on the pressure drag.
      However, the air cavity trapping occurs above a critical impact velocity which
      for the superhydrophobic spheres is significantly lower than that pertaining to
      the hydrophobic one; thus a certain range of impact velocities exists at which
      the superhydrophobic sphere experiences a lower pressure drag and a higher mean
      velocity. As soon as the air cavity vanishes, the dynamics of the
      superhydrophobic sphere becomes indistinguishable from that of the hydrophobic
      one, in spite of the persistence of air within the surface micro-texture.

PMID- 30222136
TI  - Endothelial pyruvate kinase M2 maintains vascular integrity.
AB  - The M2 isoform of pyruvate kinase (PKM2) is highly expressed in most cancer
      cells, and has been studied extensively as a driver of oncogenic metabolism. In
      contrast, the role of PKM2 in nontransformed cells is little studied, and nearly
      nothing is known of its role, if any, in quiescent cells. We show here that
      endothelial cells express PKM2 almost exclusively over PKM1. In proliferating
      endothelial cells, PKM2 is required to suppress p53 and maintain cell cycle
      progression. In sharp contrast, PKM2 has a strikingly different role in quiescent
      endothelial cells, where inhibition of PKM2 leads to degeneration of tight
      junctions and barrier function. Mechanistically, PKM2 regulates barrier function
      independently of its canonical activity as a pyruvate kinase. Instead, PKM2
      suppresses NF-kB and its downstream target, the vascular permeability factor
      angiopoietin 2. As a consequence, loss of endothelial cell PKM2 in vivo
      predisposes mice to VEGF-induced vascular leak, and to severe bacteremia and
      death in response to sepsis. Together, these data demonstrate new roles of PKM2
      in quiescent cells, and highlight the need for caution in developing cancer
      therapies that target PKM2.

PMID- 30222134
TI  - Schwann cell-derived periostin promotes autoimmune peripheral polyneuropathy via
      macrophage recruitment.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barre
      syndrome (GBS) are inflammatory neuropathies that affect humans and are
      characterized by peripheral nerve myelin destruction and macrophage-containing
      immune infiltrates. In contrast to the traditional view that the peripheral nerve
      is simply the target of autoimmunity, we report here that peripheral nerve
      Schwann cells exacerbate the autoimmune process through extracellular matrix
      (ECM) protein induction. In a spontaneous autoimmune peripheral polyneuropathy
      (SAPP) mouse model of inflammatory neuropathy and CIDP nerve biopsies, the ECM
      protein periostin (POSTN) was upregulated in affected sciatic nerves and was
      primarily expressed by Schwann cells. Postn deficiency delayed the onset and
      reduced the extent of neuropathy, as well as decreased the number of macrophages
      infiltrating the sciatic nerve. In an in vitro assay, POSTN promoted macrophage
      chemotaxis in an integrin-AM (ITGAM) and ITGAV-dependent manner. The PNS
      infiltrating macrophages in SAPP-affected nerves were pathogenic, since depletion
      of macrophages protected against the development of neuropathy. Our findings show
      that Schwann cells promote macrophage infiltration by upregulating Postn and
      suggest that POSTN is a novel target for the treatment of macrophage-associated
      inflammatory neuropathies.

PMID- 30222135
TI  - Ubiquitin ligase RNF8 suppresses Notch signaling to regulate mammary development
      and tumorigenesis.
AB  - The E3 ubiquitin ligase RNF8 plays critical roles in maintaining genomic
      stability by promoting the repair of DNA double-strand breaks (DSBs) through
      ubiquitin signaling. Abnormal activation of Notch signaling and defective repair
      of DSBs promote breast cancer risk. Here, we found that low expression of the
      full-length RNF8 correlated with poor prognosis for breast cancer patients. Our
      data revealed that in addition to its role in the repair of DSBs, RNF8 regulated
      Notch1 signaling and cell-fate determination of mammary luminal progenitors.
      Mechanistically, RNF8 acted as a negative regulator of Notch signaling by
      ubiquitylating the active NOTCH1 protein (N1ICD), leading to its degradation.
      Consistent with abnormal activation of Notch signaling and impaired repair of
      DSBs in Rnf8-mutant mammary epithelial cells, we observed increased risk of
      mammary tumorigenesis in mouse models for RNF8 deficiency. Notably, deficiency of
      RNF8 sensitized breast cancer cells to combination of pharmacological inhibitors
      of Notch signaling and poly(ADP-ribose) polymerase (PARP), suggesting
      implications for treatment of breast cancer associated with impaired RNF8
      expression or function.

PMID- 30222137
TI  - JAK2/IDH-mutant-driven myeloproliferative neoplasm is sensitive to combined
      targeted inhibition.

PMID- 30222139
TI  - Entering the spotlight: hepatitis B surface antigen-specific B cells.
AB  - Hepatitis B virus-specific (HBV-specific) T cells have been identified as main
      effector cells in HBV clearance. In contrast, B cells producing neutralizing
      antibodies against the HBV surface antigen (HBsAg) have been studied in little
      detail, mainly due to methodical limitations. In this issue of the JCI, two
      reports use a new technique to specifically detect and characterize HBsAg
      specific B cells ex vivo. Indeed, these cells are present, but show phenotypic
      alterations and impaired function during acute and chronic HBV infection. Thus,
      HBsAg-specific B cells are a novel attractive target for antiviral strategies
      toward functional cure of chronic HBV infection.

PMID- 30222138
TI  - Inhibition of neogenin fosters resolution of inflammation and tissue
      regeneration.
AB  - The resolution of inflammation is an active process that is coordinated by
      endogenous mediators. Previous studies have demonstrated the immunomodulatory
      properties of the axonal guidance proteins in the initial phase of acute
      inflammation. We hypothesized that the neuronal guidance protein neogenin (Neo1)
      modulates mechanisms of inflammation resolution. In murine peritonitis, Neo1
      deficiency (Neo1-/-) resulted in higher efficacies in reducing neutrophil
      migration into injury sites, increasing neutrophil apoptosis, actuating PMN
      phagocytosis, and increasing the endogenous biosynthesis of specialized
      proresolving mediators, such as lipoxin A4, maresin-1, and protectin DX. Neo1
      expression was limited to Neo1-expressing Ly6Chi monocytes, and Neo1 deficiency
      induced monocyte polarization toward an antiinflammatory and proresolving
      phenotype. Signaling network analysis revealed that Neo1-/- monocytes mediate
      their immunomodulatory effects specifically by activating the PI3K/AKT pathway
      and suppressing the TGF-beta pathway. In a cohort of 59 critically ill, intensive
      care unit (ICU) pediatric patients, we found a strong correlation between Neo1
      blood plasma levels and abdominal compartment syndrome, Pediatric Risk of
      Mortality III (PRISM-III) score, and ICU length of stay and mortality. Together,
      these findings identify a crucial role for Neo1 in regulating tissue regeneration
      and resolution of inflammation, and determined Neo1 to be a predictor of
      morbidity and mortality in critically ill children affected by clinical
      inflammation.

PMID- 30222140
TI  - CD122 signaling in CD8+ memory T cells drives costimulation-independent
      rejection.
AB  - Interrupting T cell costimulatory signals as a strategy to control undesired
      immune responses, such as occur in autoimmunity or transplantation, has the
      potential to alleviate many of the unwanted side effects associated with current
      immunosuppressive therapies. Belatacept, a high-affinity version of CTLA4-Ig that
      blocks ligand ligation to CD28, has been approved for use in kidney transplant
      recipients. Despite the long-term benefits associated with its use, such as
      improved renal function and lower cardiovascular risk, a subset of patients
      treated with belatacept experience elevated rates of acute T cell-mediated
      rejection, tempering enthusiasm for its use. Here we demonstrate that
      costimulation-independent T cell alloreactivity relies on signaling through
      CD122, the shared IL-2 and IL-15 receptor beta-chain. Combined costimulatory and
      CD122 blockade improved survival of transplanted tissue in mice and nonhuman
      primates by controlling proliferation and effector function of CD8+ T cells. The
      high-affinity IL-2 receptor was dispensable for memory CD8+ T cell responses,
      whereas signaling through CD122 as a component of the high-affinity IL-15
      receptor was critical for costimulation-independent memory CD8+ T cell recall,
      distinguishing specific roles for IL-2 and IL-15 in T cell activation. These
      studies outline a novel approach for clinical optimization of costimulatory
      blockade strategies in transplantation by targeting CD122.

PMID- 30222142
TI  - Preparation of a High-quality Primary Cell Culture from Fish Pituitaries.
AB  - Primary cell culture is a powerful tool commonly used by scientists to study
      cellular properties and mechanisms of isolated cells in a controlled environment.
      Despite vast differences in the physiology between mammals and fish, primary cell
      culture protocols from fish are often based on mammalian culture conditions,
      often with only minor modifications. The environmental differences affect not
      only body temperature, but also blood serum parameters such as osmolality, pH,
      and pH buffer capacity. As cell culture media and similar working solutions are
      meant to mimic characteristics of the extracellular fluid and/or blood serum to
      which a cell is adapted, it is crucial that these parameters are adjusted
      specifically to the animal in question. The current protocol describes optimized
      primary culture conditions for medaka (Oryzias latipes). The protocol provides
      detailed steps on how to isolate and maintain healthy dissociated pituitary cells
      for more than one week and includes the following steps: 1. the adjustment of the
      osmolality to the values found in medaka blood plasma, 2. the adjustment of the
      incubation temperature to normal medaka temperature (here in the aquarium
      facility), and 3. the adjustment of the pH and bicarbonate buffer to values
      comparable to other fish species living at similar temperatures. The results
      presented using the described protocol promote physiologically meaningful results
      for medaka and can be used as a reference guide by scientists making primary cell
      cultures from other non-mammalian species.

PMID- 30222143
TI  - Dynamic Proteomic and miRNA Analysis of Polysomes from Isolated Mouse Heart After
      Langendorff Perfusion.
AB  - Studies in dynamic changes in protein translation require specialized methods.
      Here we examined changes in newly-synthesized proteins in response to ischemia
      and reperfusion using the isolated perfused mouse heart coupled with polysome
      profiling. To further understand the dynamic changes in protein translation, we
      characterized the mRNAs that were loaded with cytosolic ribosomes (polyribosomes
      or polysomes) and also recovered mitochondrial polysomes and compared mRNA and
      protein distribution in the high-efficiency fractions (numerous ribosomes
      attached to mRNA), low-efficiency (fewer ribosomes attached) which also included
      mitochondrial polysomes, and the non-translating fractions. miRNAs can also
      associate with mRNAs that are being translated, thereby reducing the efficiency
      of translation, we examined the distribution of miRNAs across the fractions. The
      distribution of mRNAs, miRNAs, and proteins was examined under basal perfused
      conditions, at the end of 30 min of global no-flow ischemia, and after 30 min of
      reperfusion. Here we present the methods used to accomplish this analysis-in
      particular, the approach to optimization of protein extraction from the sucrose
      gradient, as this has not been described before-and provide some representative
      results.

PMID- 30222144
TI  - A Standard and Reliable Method to Fabricate Two-Dimensional Nanoelectronics.
AB  - Two-dimensional (2D) materials have attracted huge attention due to their unique
      properties and potential applications. Since wafer scale synthesis of 2D
      materials is still in nascent stages, scientists cannot fully rely on traditional
      semiconductor techniques for related research. Delicate processes from locating
      the materials to electrode definition need to be well controlled. In this
      article, a universal fabrication protocol required in manufacturing nanoscale
      electronics, such as 2D quasi-heterojunction bipolar transistors (Q-HBT), and 2D
      back-gated transistors are demonstrated. This protocol includes the determination
      of material position, electron beam lithography (EBL), metal electrode
      definition, et al. A step by step narrative of the fabrication procedures for
      these devices are also presented. Furthermore, results show that each of the
      fabricated devices has achieved high performance with high repeatability. This
      work reveals a comprehensive description of process flow for preparing 2D nano
      electronics, enables the research groups to access this information, and pave the
      way toward future electronics.

PMID- 30222141
TI  - Use of contraceptive depot medroxyprogesterone acetate is associated with
      impaired cervicovaginal mucosal integrity.
AB  - BACKGROUND: Injectable depot medroxyprogesterone acetate (DMPA) is one of the
      most popular contraception methods in areas of high HIV seroprevalence. Evidence
      is accumulating that use of DMPA might be associated with an increased risk of
      HIV-1 acquisition by women; however, mechanisms of this association are not
      completely understood. The goal of this study was to gain insight into mechanisms
      underlying the possible link between use of DMPA and risk of HIV-1 acquisition,
      exploring transcription profiling of ectocervical tissues. METHODS: Healthy women
      received either DMPA (n = 31) or combined oral contraceptive (COC), which has not
      been linked to an increased risk of HIV acquisition (n = 32). We conducted a
      comparative microarray-based whole-genome transcriptome profiling of human
      ectocervical tissues before and after 6 weeks of hormonal contraception use.
      RESULTS: The analysis identified that expression of 235 and 76 genes was
      significantly altered after DMPA and COC use, respectively. The most striking
      effect of DMPA, but not COC, was significantly altered expression (mostly
      downregulation) of many genes strategically involved in the maintenance of
      mucosal barrier function; the alterations, as indicated by Ingenuity Pathway
      Analysis (IPA), were most likely due to the DMPA-induced estrogen deficiency.
      Furthermore, IPA predicted that transcriptome alterations related to ectocervical
      immune responses were in general compatible with an immunosuppressive effect of
      DMPA, but, in some women, also with an inflammatory-like response. CONCLUSION:
      Our results suggest that impairment of cervicovaginal mucosal integrity in
      response to DMPA administration is an important mechanism contributing to the
      potential increased risk of HIV-1 acquisition in DMPA users. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01421368. FUNDING: This study was supported by the United
      States Agency for International Development (USAID) under Cooperative Agreement
      GPO-A-00-08-00005-00.

PMID- 30222145
TI  - Using Rapid Serial Visual Presentation to Measure Set-Specific Capture, a
      Consequence of Distraction While Multitasking.
AB  - This method uses a rapid serial visual presentation (RSVP) paradigm to measure
      the cost of distraction when participants maintain multiple search goals. The
      protocol identifies two types of distraction within a single task - contingent
      attentional capture and set-specific capture - that represent different types of
      limitations of cognitive processing. Participants search for letters in two or
      more "target" ink colors (e.g., green and orange) within a continuous RSVP stream
      of heterogeneously colored letters, while ignoring two peripheral RSVPs of
      letters. Upon detecting a target, participants are to identify the letter. On
      some trials, target-colored distractors appear in the periphery just prior to the
      presentation of a target, causing a drop in target identification performance.
      Contingent attentional capture is observed by examining performance on trials in
      which the peripheral distractor is the same color as the target on that trial
      (e.g., both orange). Set-specific capture is represented by performance on trials
      in which the peripheral distractor is target-colored (e.g., orange), but not the
      same color as the target on that trial (e.g., green.) By varying the amount of
      time (i.e., the number of stimuli appearing) between the presentation of the
      distractor and the target, researchers can observe how participants recover from
      these distraction costs over time. As compared to static displays that are often
      used to measure contingent attentional capture, the dynamic display produces much
      larger effects, allowing the researcher to identify subtle effects of smaller
      manipulations. An unusual aspect of our design is that it employs a continuous
      display; "filler" stimuli connect one trial to the next seamlessly, and
      participants respond during this interval whenever they detect a target. The
      continuous display reduces chance performance to near-zero levels (rather than
      50%) and provides researchers with a more sensitive measure of performance
      differences across trial types.

PMID- 30222146
TI  - A Proximal Culture Method to Study Paracrine Signaling Between Cells.
AB  - Intercellular interactions play an important role in many biological processes,
      including tumor progression, immune responses, angiogenesis, and development.
      Paracrine or juxtacrine signaling mediates such interactions. The use of a
      conditioned medium and coculture studies are the most common methods to
      discriminate between these two types of interactions. However, the effect of
      localized high concentrations of secreted factors in the microenvironment during
      the paracrine interactions is not accurately recapitulated by conditioned medium
      and, thus, may lead to imprecise conclusions. To overcome this problem, we have
      devised a proximal culture method to study paracrine signaling. The two cell
      types are grown on either surface of a 10 um-thick polycarbonate membrane with
      0.4 um pores. The pores allow the exchange of secreted factors and, at the same
      time, inhibit juxtacrine signaling. The cells can be collected and lysed at the
      endpoint to determine the effects of the paracrine signaling. In addition to
      allowing for localized concentration gradients of secreted factors, this method
      is amenable to experiments involving prolonged periods of culture, as well as the
      use of inhibitors. While we use this method to study the interactions between
      ovarian cancer cells and the mesothelial cells they encounter at the site of
      metastasis, it can be adapted to any two adherent cell types for researchers to
      study paracrine signaling in various fields, including tumor microenvironment,
      immunology, and development.

PMID- 30222147
TI  - Isolating and Incorporating Light-Harvesting Antennas from Diatom Cyclotella
      Meneghiniana in Liposomes with Thylakoid Lipids.
AB  - The photosynthetic performance of plants, algae and diatoms strongly depends on
      the fast and efficient regulation of the light harvesting and energy transfer
      processes in the thylakoid membrane of chloroplasts. The light harvesting antenna
      of diatoms, the so called fucoxanthin chlorophyll a/c binding proteins (FCP), are
      required for the light absorption and efficient transfer to the photosynthetic
      reaction centers as well as for photo-protection from excessive light. The switch
      between these two functions is a long-standing matter of research. Many of these
      studies have been carried out with FCP in detergent micelles. For interaction
      studies, the detergents have been removed, which led to an unspecific aggregation
      of FCP complexes. In this approach, it is hard to discriminate between artifacts
      and physiologically relevant data. Hence, more valuable information about FCP and
      other membrane bound light harvesting complexes can be obtained by studying
      protein-protein interactions, energy transfer and other spectroscopic features if
      they are embedded in their native lipid environment. The main advantage is that
      liposomes have a defined size and a defined lipid/protein ratio by which the
      extent of FCP clustering is controlled. Further, changes in the pH and ion
      composition that regulate light harvesting in vivo can easily be simulated. In
      comparison to the thylakoid membrane, the liposomes are more homogenous and less
      complex, which makes it easier to obtain and understand spectroscopic data. The
      protocol describes the procedure of FCP isolation and purification, liposome
      preparation, and incorporation of FCP into liposomes with natural lipid
      composition. Results from a typical application are given and discussed.

PMID- 30222148
TI  - Maintaining Biological Cultures and Measuring Gene Expression in Aphis nerii: A
      Non-model System for Plant-insect Interactions.
AB  - Aphids are excellent experimental models for a variety of biological questions
      ranging from the evolution of symbioses and the development of polyphenisms to
      questions surrounding insect's interactions with their host plants. Genomic
      resources are available for several aphid species, and with advances in the next
      generation sequencing, transcriptomic studies are being extended to non-model
      organisms that lack genomes. Furthermore, aphid cultures can be collected from
      the field and reared in the laboratory for the use in organismal and molecular
      experiments to bridge the gap between ecological and genetic studies. Last, many
      aphids can be maintained in the laboratory on their preferred host plants in
      perpetual, parthenogenic life cycles allowing for comparisons of asexually
      reproducing genotypes. Aphis nerii, the milkweed-oleander aphid, provides one
      such model to study insect interactions with toxic plants using both organismal
      and molecular experiments. Methods for the generation and maintenance of the
      plant and aphid cultures in the greenhouse and laboratory, DNA and RNA
      extractions, microsatellite analysis, de novo transcriptome assembly and
      annotation, transcriptome differential expression analysis, and qPCR verification
      of differentially expressed genes are outlined and discussed here.

PMID- 30222149
TI  - Live-Cell Imaging Assays to Study Glioblastoma Brain Tumor Stem Cell Migration
      and Invasion.
AB  - Glioblastoma (GBM) is an aggressive brain tumor that is poorly controlled with
      the currently available treatment options. Key features of GBMs include rapid
      proliferation and pervasive invasion into the normal brain. Recurrence is thought
      to result from the presence of radio- and chemo-resistant brain tumor stem cells
      (BTSCs) that invade away from the initial cancerous mass and, thus, evade
      surgical resection. Hence, therapies that target BTSCs and their invasive
      abilities may improve the otherwise poor prognosis of this disease. Our group and
      others have successfully established and characterized BTSC cultures from GBM
      patient samples. These BTSC cultures demonstrate fundamental cancer stem cell
      properties such as clonogenic self-renewal, multi-lineage differentiation, and
      tumor initiation in immune-deficient mice. In order to improve on the current
      therapeutic approaches for GBM, a better understanding of the mechanisms of BTSC
      migration and invasion is necessary. In GBM, the study of migration and invasion
      is restricted, in part, due to the limitations of existing techniques which do
      not fully account for the in vitro growth characteristics of BTSCs grown as
      neurospheres. Here, we describe rapid and quantitative live-cell imaging assays
      to study both the migration and invasion properties of BTSCs. The first method
      described is the BTSC migration assay which measures the migration toward a
      chemoattractant gradient. The second method described is the BTSC invasion assay
      which images and quantifies a cellular invasion from neurospheres into a matrix.
      The assays described here are used for the quantification of BTSC migration and
      invasion over time and under different treatment conditions.

PMID- 30222150
TI  - Luminophore Formation in Various Conformations of Bovine Serum Albumin by Binding
      of Gold(III).
AB  - The purpose of the presented protocols is to study the process of Au(III) binding
      to BSA, yielding conformation change-induced red fluorescence (lambdaem = 640 nm)
      of BSA-Au(III) complexes. The method adjusts the pH to show that the emergence of
      the red fluorescence is correlated with the pH-induced equilibrium transitions of
      the BSA conformations. Red fluorescent BSA-Au(III) complexes can only be formed
      with an adjustment of pH at or above 9.7, which corresponds to the "A-form"
      conformation of BSA. The protocol to adjust the BSA to Au molar ratio and to
      monitor the time-course of the process of Au(III) binding is described. The
      minimum number of Au(III) per BSA, to produce the red fluorescence, is less than
      seven. We describe the protocol in steps to illustrate the presence of multiple
      Au(III) binding sites in BSA. First, by adding copper (Cu(II)) or nickel (Ni(II))
      cations followed by Au(III), this method reveals a binding site for Au(III) that
      is not the red fluorophore. Second, by modifying BSA by thiol capping agents,
      another nonfluorophore-forming Au(III) binding site is revealed. Third, changing
      the BSA conformation by cleaving and capping of the disulfide bonds, the possible
      Au(III) binding site(s) are illustrated. The protocol described, to control the
      BSA conformations and Au(III) binding, can be generally applied to study the
      interactions of other proteins and metal cations.

PMID- 30222151
TI  - Identifying Coronary Artery Calcification on Non-gated Computed Tomography Scans.
AB  - Coronary artery calcification (CAC) provides an objective measure of coronary
      artery disease and can readily be identified on non-gated computed tomography
      (CT) scans with a high correlation with gated cardiac CT scans. This standardized
      protocol takes a step-wise approach to not only optimizing an image for the
      identification of calcification but also to distinguishing CAC from other common
      causes of calcification in the cardiac silhouette. Recognition of CAC on non
      gated CT scans helps to identify a very powerful prognostic factor that can
      influence therapeutic interventions or downstream diagnostic testing without
      requiring a gated cardiac scan. These non-gated CT scans are often acquired as
      part of the routine care of the patient, and this data is readily available
      without another dose of ionizing radiation. This protocol allows for the precise
      and accurate extraction of this data for the purposes of retrospective data
      analysis in clinical research studies, but also in the clinical evaluation and
      management of patients.

PMID- 30222152
TI  - The Effect of Ultraviolet Radiation on the Chemical Bath Deposition of
      Bis(thiourea) Cadmium Chloride Crystals and the Subsequent CdS Obtention.
AB  - In this work, the effects on the preparation of bis(thiourea) cadmium chloride
      crystals when illuminated with ultraviolet (UV) light at a wavelength of 367 nm
      using the chemical bath deposition technique are studied comparatively. Two
      experiments are performed to make a comparison: one without UV light and the
      other with the aid of UV light. Both experiments are performed under equal
      conditions, at a temperature of 343 K and with a pH of 3.2. The precursors used
      are cadmium chloride (CdCl2) and thiourea [CS(NH2)2], which are dissolved in 50
      mL of deionized water with an acidic pH. In this experiment, the interaction of
      electromagnetic radiation is sought at the moment the chemical reaction is
      carried out. The results demonstrate the existence of an interaction between the
      crystals and the UV light; the UV light assistance causes crystal growths in an
      acicular shape. Also, the final product obtained is cadmium sulfide and shows no
      evident difference when synthesized with or without the use of UV light.

PMID- 30222153
TI  - In Situ Hybridization Techniques for Paraffin-Embedded Adult Coral Samples.
AB  - Corals are important ocean invertebrates that are critical for overall ocean
      health as well as human health. However, due to human impacts such as rising
      ocean temperatures and ocean acidification, corals are increasingly under threat.
      To tackle these challenges, advances in cell and molecular biology have proven to
      be crucial for diagnosing the health of corals. Modifying some of the techniques
      commonly used in human medicine could greatly improve researchers' ability to
      treat and save corals. To address this, a protocol for in situ hybridization used
      primarily in human medicine and evolutionary developmental biology has been
      adapted for use in adult corals under stress. The purpose of this method is to
      visualize the spatial expression of an RNA probe in adult coral tissue that has
      been embedded in paraffin and sectioned onto glass slides. This method focuses on
      removal of the paraffin and rehydration of the sample, pretreatment of the sample
      to ensure permeability of the sample, pre-hybridization incubation, hybridization
      of the RNA probe, and visualization of the RNA probe. This is a powerful method
      when using non-model organisms to discover where specific genes are expressed,
      and the protocol can be easily adapted for other non-model organisms. However,
      the method is limited in that it is primarily qualitative, because expression
      intensity can vary depending on the amount of time used during the visualization
      step and the concentration of the probe. Furthermore, patience is required, as
      this protocol can take up to 5 days (and in many cases, longer) depending on the
      probe being used. Finally, non-specific background staining is common, but this
      limitation can be overcome.

PMID- 30222154
TI  - Fabrication and Testing of Catalytic Aerogels Prepared Via Rapid Supercritical
      Extraction.
AB  - Protocols for preparing and testing catalytic aerogels by incorporating metal
      species into silica and alumina aerogel platforms are presented. Three
      preparation methods are described: (a) the incorporation of metal salts into
      silica or alumina wet gels using an impregnation method; (b) the incorporation of
      metal salts into alumina wet gels using a co-precursor method; and (c) the
      addition of metal nanoparticles directly into a silica aerogel precursor mixture.
      The methods utilize a hydraulic hot press, which allows for rapid (<6 h)
      supercritical extraction and results in aerogels of low density (0.10 g/mL) and
      high surface area (200-800 m2/g). While the work presented here focuses on the
      use of copper salts and copper nanoparticles, the approach can be implemented
      using other metal salts and nanoparticles. A protocol for testing the three-way
      catalytic ability of these aerogels for automotive pollution mitigation is also
      presented. This technique uses custom-built equipment, the Union Catalytic
      Testbed (UCAT), in which a simulated exhaust mixture is passed over an aerogel
      sample at a controlled temperature and flow rate. The system is capable of
      measuring the ability of the catalytic aerogels, under both oxidizing and
      reducing conditions, to convert CO, NO and unburned hydrocarbons (HCs) to less
      harmful species (CO2, H2O and N2). Example catalytic results are presented for
      the aerogels described.

PMID- 30222155
TI  - Evaluating Dryocosmus Kuriphilus-induced Damage on Castanea Sativa.
AB  - Dryocosmus kuriphilus Yasumatsu has become a major pest for Castaneasativa since
      its arrival in Europe. Its galling activity results in the formation of different
      gall types and prevents the development of normal shoots. Repeated and
      uncontrolled attacks cause, besides the production of galls and the attendant
      gall-related reduction in leaf area, progressive corruption of the branch
      architecture, including the death of branch parts, and an increase in dormant bud
      activation. Thus far, there have been few attempts to quantify branch
      architecture damage. Further, the different methods for assessing infestation
      degree (MAID) that have been developed focus only on the galls' presence and
      abundance. Using the leaf area to sapwood area relationship as a green biomass
      indicator, we developed in a previous study a damage composite index (DCI) that
      takes into account the most important branch architectural features, allowing for
      realistic damage assessment during the entire epidemic process. The aim of this
      study is to present this novel method and highlight differences in the damage
      description with respect to other broadly used indices. Results show how the DCI
      depicts branch damage better, especially during the epidemic peak, compared to
      MAID, which tend to underestimate it. We conclude by suggesting how to properly
      evaluate the overall impact of the pest by means of our composite damage index,
      the infestation degree using classic methods, and crown transparency evaluations.

PMID- 30222156
TI  - Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of
      Antibiotics in Critical Illnesses.
AB  - There is an ever-increasing demand for the therapeutic drug monitoring of
      antibiotics in many clinical facilities, particularly with regard to the
      implementation of hospital antibiotic stewardship programs. In the current work,
      we present a multiplex high-performance liquid chromatography-tandem mass
      spectrometry (HPCL-MS/MS) protocol for the quantification of cefepime, meropenem,
      ciprofloxacin, moxifloxacin, linezolid, and piperacillin, commonly used
      antibiotics in intensive care units. The method was previously comprehensively
      validated according to the guideline of the European Medicines Agency. After a
      rapid sample cleanup, the analytes are separated on a C8 reverse-phase HPLC
      column within 4 minutes and quantified with the corresponding stable isotope
      labeled internal standards in electrospray ionization (ESI+) mass spectrometry in
      multiple reaction time monitoring (MRM). The presented method uses a simple
      instrumentation setting with uniform chromatographic conditions, allowing for the
      daily and robust antibiotic therapeutic drug monitoring in clinical laboratories.
      The calibration curve spans the pharmacokinetic concentration range, thereby
      including antibiotic amounts close to the minimal inhibitory concentration (MIC)
      of susceptible bacteria and peak concentrations (Cmax) that are obtained with
      bolus administration regimens. Without the necessity of the serum dilution before
      the sample cleanup, the area under the curve for an administered antibiotic can
      be obtained through multiple measurements.

PMID- 30222158
TI  - A Novel Single Animal Motor Function Tracking System Using Simple, Readily
      Available Software.
AB  - We have recently demonstrated that implanting intracortical microelectrodes in
      the motor corteces of rats results in immediate and lasting motor deficits. Motor
      impairments were manually quantified through an open field grid test to measure
      the gross motor function and through a ladder test to measure the fine motor
      function. Here, we discuss a technique for the automated quantification of the
      video-recorded tests using our custom Capadona Behavioral Video Analysis System:
      Grid and Ladder Test, or BVAS. Leveraging simple and readily available coding
      software (see the Table of Materials), this program allows for the tracking of a
      single animal on both the open field grid and the ladder tests. In open field
      grid tracking, the code thresholds the video for intensity, tracks the position
      of the rat over the 3 min duration of the grid test, and analyzes the path. It
      then computes and returns measurements for the total distance traveled, the
      maximum velocity achieved, the number of left- and right-handed turns, and the
      total number of grid lines crossed by the rat. In ladder tracking, the code again
      thresholds the video for intensity, tracks the movement of the rat across the
      ladder, and returns calculated measurements including the time it took the rat to
      cross the ladder, the number of paw slips occurring below the plane of the ladder
      rungs, and the incidence of failures due to stagnation or reversals. We envision
      that the BVAS developed here can be employed for the analysis of motor function
      in a variety of applications, including many injury or disease models.

PMID- 30222157
TI  - Efficient Production and Identification of CRISPR/Cas9-generated Gene Knockouts
      in the Model System Danio rerio.
AB  - Characterization of the clustered, regularly interspaced, short, palindromic
      repeat (CRISPR) system of Streptococcus pyogenes has enabled the development of a
      customizable platform to rapidly generate gene modifications in a wide variety of
      organisms, including zebrafish. CRISPR-based genome editing uses a single guide
      RNA (sgRNA) to target a CRISPR-associated (Cas) endonuclease to a genomic DNA
      (gDNA) target of interest, where the Cas endonuclease generates a double-strand
      break (DSB). Repair of DSBs by error-prone mechanisms lead to insertions and/or
      deletions (indels). This can cause frameshift mutations that often introduce a
      premature stop codon within the coding sequence, thus creating a protein-null
      allele. CRISPR-based genome engineering requires only a few molecular components
      and is easily introduced into zebrafish embryos by microinjection. This protocol
      describes the methods used to generate CRISPR reagents for zebrafish
      microinjection and to identify fish exhibiting germline transmission of CRISPR
      modified genes. These methods include in vitro transcription of sgRNAs,
      microinjection of CRISPR reagents, identification of indels induced at the target
      site using a PCR-based method called a heteroduplex mobility assay (HMA), and
      characterization of the indels using both a low throughput and a powerful next
      generation sequencing (NGS)-based approach that can analyze multiple PCR products
      collected from heterozygous fish. This protocol is streamlined to minimize both
      the number of fish required and the types of equipment needed to perform the
      analyses. Furthermore, this protocol is designed to be amenable for use by
      laboratory personal of all levels of experience including undergraduates,
      enabling this powerful tool to be economically employed by any research group
      interested in performing CRISPR-based genomic modification in zebrafish.

PMID- 30222159
TI  - Producing Gene Deletions in Escherichia coli by P1 Transduction with Excisable
      Antibiotic Resistance Cassettes.
AB  - A first approach to study the function of an unknown gene in bacteria is to
      create a knock-out of this gene. Here, we describe a robust and fast protocol for
      transferring gene deletion mutations from one Escherichia coli strain to another
      by using generalized transduction with the bacteriophage P1. This method requires
      that the mutation be selectable (e.g., based on gene disruptions using antibiotic
      cassette insertions). Such antibiotic cassettes can be mobilized from a donor
      strain and introduced into a recipient strain of interest to quickly and easily
      generate a gene deletion mutant. The antibiotic cassette can be designed to
      include flippase recognition sites that allow the excision of the cassette by a
      site-specific recombinase to produce a clean knock-out with only a ~100-base-pair
      long scar sequence in the genome. We demonstrate the protocol by knocking out the
      tamA gene encoding an assembly factor involved in autotransporter biogenesis and
      test the effect of this knock-out on the biogenesis and function of two trimeric
      autotransporter adhesins. Though gene deletion by P1 transduction has its
      limitations, the ease and speed of its implementation make it an attractive
      alternative to other methods of gene deletion.

PMID- 30222160
TI  - A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover
      Protease PCSK9.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a single-turnover
      protease which regulates serum low-density lipoprotein (LDL) levels and,
      consequently, cardiovascular disease. Although PCSK9 proteolysis is required for
      its full hypercholesterolemic effect, the evaluation of its proteolytic function
      is challenging: PCSK9 is only known to cleave itself, undergoes only a single
      turnover, and after proteolysis, retains its substrate in its active site as an
      auto-inhibitor. The methods presented here describe an assay which overcomes
      these challenges. The assay focuses on intermolecular proteolysis in a cell-based
      context and links successful cleavage to the secreted luciferase activity, which
      can be easily read out in the conditioned medium. Via sequential steps of
      mutagenesis, transient transfection, and a luciferase readout, the assay can
      probe PCSK9 proteolysis under conditions of either genetic or molecular
      perturbation in a high-throughput manner. This system is well suited for both the
      biochemical evaluation of clinically discovered missense single-nucleotide
      polymorphisms (SNPs), as well as for the screening of small-molecule inhibitors
      of PCSK9 proteolysis.

PMID- 30222162
TI  - Isolation of Human Endometrial Stromal Cells for In Vitro Decidualization.
AB  - The differentiation of human endometrial stromal cells (HESC) from fibroblast
      like appearance into secretory decidua is a transformation required for embryo
      implantation into the uterine lining of the maternal womb. Improper
      decidualization has been established as a root cause for implantation failure and
      subsequent early embryo miscarriage. Therefore, understanding the molecular
      mechanisms underlying decidualization is advantageous to improving the rate of
      successful births. In vivo based studies of artificial decidualization are often
      limiting due to ethical dilemmas associated with human research, as well as
      translational complications within animal models. As a result, in vitro assays
      through primary cell culture are often utilized to explore the modulation of
      decidualization via hormones. This study provides a detailed protocol for the
      isolation of HESC and subsequent artificial decidualization via the
      supplementation of hormones to the culturing medium. Further, this study provides
      a well-designed method to knockdown any gene of interest by utilizing lipid-based
      siRNA transfections. This protocol permits the optimization of culture purity as
      well as product yield, thereby maximizing the ability to utilize this model as a
      reliable method to understand the molecular mechanisms underlying
      decidualization, and the subsequent quantification of secreted agents by
      decidualized endometrial stromal cells.

PMID- 30222161
TI  - Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in
      Developing and Postmitotic Mouse Retina.
AB  - The epigenetics of retinal development is a well-studied research field, which
      promises to bring a new level of understanding about the mechanisms of a variety
      of human retinal degenerative diseases and pinpoint new treatment approaches. The
      nuclear architecture of mouse retina is organized in two different patterns:
      conventional and inverted. Conventional pattern is universal where
      heterochromatin is localized to the periphery of the nucleus, while active
      euchromatin resides in the nuclear interior. In contrast, inverted nuclear
      pattern is unique to the adult rod photoreceptor cell nuclei where
      heterochromatin localizes to the nuclear center, and euchromatin resides in the
      nuclear periphery. DNA methylation is predominantly observed in chromocenters.
      DNA methylation is a dynamic covalent modification on the cytosine residues (5
      methylcytosine, 5mC) of CpG dinucleotides that are enriched in the promoter
      regions of many genes. Three DNA methyltransferases (DNMT1, DNMT3A and DNMT3B)
      participate in methylation of DNA during development. Detecting 5mC with
      immunohistochemical techniques is very challenging, contributing to variability
      in results, as all DNA bases including 5mC modified bases are hidden within the
      double-stranded DNA helix. However, detailed delineation of 5mC distribution
      during development is very informative. Here, we describe a reproducible
      technique for robust immunohistochemical detection of 5mC and another epigenetic
      DNA marker 5-hydroxymethylcytosine (5hmC), which colocalizes with the "open",
      transcriptionally active chromatin in developing and postmitotic mouse retina.

PMID- 30222163
TI  - Three-dimensional Printing of Thermoplastic Materials to Create Automated Syringe
      Pumps with Feedback Control for Microfluidic Applications.
AB  - Microfluidics has become a critical tool in research across the biological,
      chemical, and physical sciences. One important component of microfluidic
      experimentation is a stable fluid handling system capable of accurately providing
      an inlet flow rate or inlet pressure. Here, we have developed a syringe pump
      system capable of controlling and regulating the inlet fluid pressure delivered
      to a microfluidic device. This system was designed using low-cost materials and
      additive manufacturing principles, leveraging three-dimensional (3D) printing of
      thermoplastic materials and off-the-shelf components whenever possible. This
      system is composed of three main components: a syringe pump, a pressure
      transducer, and a programmable microcontroller. Within this paper, we detail a
      set of protocols for fabricating, assembling, and programming this syringe pump
      system. Furthermore, we have included representative results that demonstrate
      high-fidelity, feedback control of inlet pressure using this system. We expect
      this protocol will allow researchers to fabricate low-cost syringe pump systems,
      lowering the entry barrier for the use of microfluidics in biomedical, chemical,
      and materials research.

PMID- 30222164
TI  - Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of
      Orthotopic Human Glioblastoma Multiforme Xenografts.
AB  - Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain
      cancer in adults, is generally associated with a poor prognosis, and scarce
      efficient therapies have been proposed over the last decade. Among the promising
      candidates for designing novel therapeutic strategies, cellular immunotherapies
      have been targeted to eliminate highly invasive and chemo-radioresistant tumor
      cells, likely involved in a rapid and fatal relapse of this cancer. Thus,
      administration(s) of allogeneic GBM-reactive immune cell effectors, such as human
      VUpsilon9Vdelta2 T lymphocytes, in the vicinity of the tumor would represents a
      unique opportunity to deliver efficient and highly concentrated therapeutic
      agents directly into the site of brain malignancies. Here, we present a protocol
      for the preparation and the stereotaxic administration of allogeneic human
      lymphocytes in immunodeficient mice carrying orthotopic human primary brain
      tumors. This study provides a preclinical proof-of-concept for both the
      feasibility and the antitumor efficacy of these cellular immunotherapies that
      rely on stereotactic injections of allogeneic human lymphocytes within intrabrain
      tumor beds.

PMID- 30222165
TI  - Investigating Mammalian Axon Regeneration: In Vivo Electroporation of Adult Mouse
      Dorsal Root Ganglion.
AB  - Electroporation is an essential non-viral gene transfection approach to introduce
      DNA plasmids or small RNA molecules into cells. A sensory neuron in the dorsal
      root ganglion (DRGs) extends a single axon with two branches. One branch goes to
      the peripheral nerve (peripheral branch), and the other branch enters the spinal
      cord through the dorsal root (central branch). After the neural injury, the
      peripheral branch regenerates robustly whereas the central branch does not
      regenerate. Due to the high regenerative capacity, sensory axon regeneration has
      been widely used as a model system to study mammalian axon regeneration in both
      the peripheral nervous system (PNS) and the central nervous system (CNS). Here,
      we describe a previously established approach protocol to manipulate gene
      expression in mature sensory neurons in vivo via electroporation. Based on
      transfection with plasmids or small RNA oligos (siRNAs or microRNAs), the
      approach allows for both loss- and gain-of-function experiments to study the
      roles of genes-of-interests or microRNAs in regulation of axon regeneration in
      vivo. In addition, the manipulation of gene expression in vivo can be controlled
      both spatially and temporally within a relatively short time course. This model
      system provides a unique tool to investigate the molecular mechanisms by which
      mammalian axon regeneration is regulated in vivo.

PMID- 30222166
TI  - Virtual Reality Experiments with Physiological Measures.
AB  - Virtual reality (VR) experiments are increasingly employed because of their
      internal and external validity compared to real-world observation and laboratory
      experiments, respectively. VR is especially useful for geographic visualizations
      and investigations of spatial behavior. In spatial behavior research, VR provides
      a platform for studying the relationship between navigation and physiological
      measures (e.g., skin conductance, heart rate, blood pressure). Specifically,
      physiological measures allow researchers to address novel questions and constrain
      previous theories of spatial abilities, strategies, and performance. For example,
      individual differences in navigation performance may be explained by the extent
      to which changes in arousal mediate the effects of task difficulty. However, the
      complexities in the design and implementation of VR experiments can distract
      experimenters from their primary research goals and introduce irregularities in
      data collection and analysis. To address these challenges, the Experiments in
      Virtual Environments (EVE) framework includes standardized modules such as
      participant training with the control interface, data collection using
      questionnaires, the synchronization of physiological measurements, and data
      storage. EVE also provides the necessary infrastructure for data management,
      visualization, and evaluation. The present paper describes a protocol that
      employs the EVE framework to conduct navigation experiments in VR with
      physiological sensors. The protocol lists the steps necessary for recruiting
      participants, attaching the physiological sensors, administering the experiment
      using EVE, and assessing the collected data with EVE evaluation tools. Overall,
      this protocol will facilitate future research by streamlining the design and
      implementation of VR experiments with physiological sensors.

PMID- 30222167
TI  - Classical Short-Delay Eyeblink Conditioning in One-Year-Old Children.
AB  - Classical eyeblink conditioning (EBC) refers to the learned association between a
      conditioned stimulus (an auditory tone) and an unconditioned stimulus (a puff of
      air to the cornea). Eyeblink conditioning is often used experimentally to detect
      abnormalities in cerebellar-dependent learning and memory that underlies this
      type of associative learning. While experiments in adults and older children are
      relatively simple to administer using commercial equipment, eyeblink conditioning
      in infants is more challenging due to their poor compliance, which makes correct
      positioning of the equipment difficult. To achieve conditioning in one-year-old
      infants, a custom-made or an adapted commercial system can be used to deliver the
      air puff to the infant's cornea. The main challenge lies in successfully
      detecting and classifying the behavioral responses. We report that automated
      blink detection methods are unreliable in this population, and that conditioning
      experiments should be analyzed using frame-by-frame analysis of supplementary
      video camera recordings. This method can be applied to study developmental
      changes in eyeblink conditioning and to examine whether this paradigm can detect
      children with neurological disorders.

PMID- 30222168
TI  - Disentangling High Strength Copolymer Aramid Fibers to Enable the Determination
      of Their Mechanical Properties.
AB  - Traditionally, soft body armor has been made from poly(p-phenylene
      terephthalamide) (PPTA) and ultra-high molecular weight polyethylene. However, to
      diversify the fiber choices in the United States body armor market, copolymer
      fibers based on the combination of 5-amino-2-(p-aminophenyl) benzimidazole (PBIA)
      and the more conventional PPTA were introduced. Little is known regarding the
      long-term stability of these fibers, but as condensation polymers, they are
      expected to have potential sensitivity to moisture and humidity. Therefore,
      characterizing the strength of the materials and understanding their
      vulnerability to environmental conditions is important for evaluating their use
      lifetime in safety applications. Ballistic resistance and other critical
      structural properties of these fibers are predicated on their strength. To
      accurately determine the strength of the individual fibers, it is necessary to
      disentangle them from the yarn without introducing any damage. Three aramid-based
      copolymer fibers were selected for the study. The fibers were washed with acetone
      followed by methanol to remove an organic coating that held the individual fibers
      in each yarn bundle together. This coating makes it difficult to separate single
      fibers from the yarn bundle for mechanical testing without damaging the fibers
      and affecting their strength. After washing, fourier transform infrared (FTIR)
      spectroscopy was performed on both washed and unwashed samples and the results
      were compared. This experiment has shown that there are no significant variations
      in the spectra of poly(p-phenylene-benzimidazole-terephthalamide-co-p-phenylene
      terephthalamide) (PBIA-co-PPTA1) and PBIA-co-PPTA3 after washing, and only a
      small variation in intensity for PBIA. This indicates that the acetone and
      methanol rinses are not adversely affecting the fibers and causing chemical
      degradation. Additionally, single fiber tensile testing was performed on the
      washed fibers to characterize their initial tensile strength and strain to
      failure, and compare those to other reported values. Iterative procedural
      development was necessary to find a successful method for performing tensile
      testing on these fibers.

PMID- 30222171
TI  - Recent advances in homogeneous borrowing hydrogen catalysis using earth-abundant
      first row transition metals.
AB  - The review highlights the recent advances (2013-present) in the use of earth
      abundant first row transition metals in homogeneous borrowing hydrogen catalysis.
      The utility of catalysts based on Mn, Fe, Co, Ni and Cu to promote a diverse
      array of important C-C and C-N bond forming reactions is described, including
      discussion on reaction mechanisms, scope and limitations, and future challenges
      in this burgeoning area of sustainable catalysis.

PMID- 30222169
TI  - Paired-cell sequencing enables spatial gene expression mapping of liver
      endothelial cells.
AB  - Spatially resolved single-cell RNA sequencing (scRNAseq) is a powerful approach
      for inferring connections between a cell's identity and its position in a tissue.
      We recently combined scRNAseq with spatially mapped landmark genes to infer the
      expression zonation of hepatocytes. However, determining zonation of small cells
      with low mRNA content, or without highly expressed landmark genes, remains
      challenging. Here we used paired-cell sequencing, in which mRNA from pairs of
      attached mouse cells were sequenced and gene expression from one cell type was
      used to infer the pairs' tissue coordinates. We applied this method to pairs of
      hepatocytes and liver endothelial cells (LECs). Using the spatial information
      from hepatocytes, we reconstructed LEC zonation and extracted a landmark gene
      panel that we used to spatially map LEC scRNAseq data. Our approach revealed the
      expression of both Wnt ligands and the Dkk3 Wnt antagonist in distinct
      pericentral LEC sub-populations. This approach can be used to reconstruct spatial
      expression maps of non-parenchymal cells in other tissues.

PMID- 30222172
TI  - Effect of the triazole ring in zinc porphyrin-fullerene dyads on the charge
      transfer processes in NiO-based devices.
AB  - Herein, the synthesis of three covalently linked donor-acceptor zinc porphyrin
      fullerene (ZnP-C60) dyads (C60trZnPCOOH, C60trZnPtrCOOH and C60ZnPCOOH) is
      described, and their application as sensitizers in NiO-based dye-sensitized solar
      cells (DSCs) is discussed. To the best of our knowledge, this is the first
      example where covalently linked ZnP-C60 dyads have been used as chromophores in
      NiO-based DSCs. In an effort to examine whether the distance of the chromophore
      from the electron acceptor entity and/or the NiO surface affects the performance
      of the cells, a triazole ring was introduced as a spacer between ZnP and the two
      peripheral units C60 and -COOH. The triazole ring was inserted between ZnP and
      C60 in dyad C60trZnPCOOH, whereas both the anchoring group and C60 were connected
      to ZnP through triazole spacers in C60trZnPtrCOOH, and dyad C60ZnPCOOH did not
      contain any triazole linker. Photophysical investigation performed by ultrafast
      transient absorption spectroscopy in solution and on the NiO surface demonstrated
      that all the porphyrin-fullerene dyads exhibited long-lived charge-separated
      states due to electron shifts from the reduced porphyrin core to C60. The
      transient experiments performed in solution showed that the presence of triazole
      ring influenced the photophysical properties of the dyads C60trZnPCOOH and
      C60trZnPtrCOOH and in particular, increased the lifetime of the charge-separated
      states compared to that of the C60ZnPCOOH dyad. On the other hand, the
      corresponding studies on the NiO surface proved that the triazole spacer has a
      rather moderate impact on the charge separation (NiO-ZnP+-C60-) and charge
      recombination (NiO-3*ZnP-C60) rate constants. All three dyads exhibited enhanced
      performance in terms of photovoltaic measurements with more than threefold
      increase compared to the reference compound PhtrZnPCOOH in which the C60 acceptor
      is absent. Two different electrolytes were examined (I3-/I- and CoIII/II) and in
      most cases, the presence of the triazole ring enhanced their photovoltaic
      performance. The best performing dyad in I3-/I- was C60trZnPCOOH (PCE = 0.076%);
      in CoIII/II, the best performing dyad was C60trZnPtrCOOH (PCE = 0.074%).

PMID- 30222175
TI  - Developing a magnetic metal organic framework of copper bearing a mixed
      azido/butane-1,4-dicarboxylate bridge: magnetic and gas adsorption properties.
AB  - A magnetic metal organic framework {[Cu(but-1,4-dc)0.5(N3)(H2O)].H2O}n (MFUM
      1(Cu)) (but-1,4-dc = butane-1,4-dicarboxylate) was synthesized and characterized
      structurally and magnetically. In MFUM-1(Cu), each CuII ion has a distorted
      octahedral geometry with an obvious Jahn-Teller distortion, where the
      coordination environment is composed of mixed EO-azido/aliphatic based
      carboxylate/H2O threefold bridges. These bridges extend the structure of MFUM
      1(Cu) in two dimensions by covalent connectivity and form square-shaped channels.
      Also, a study was done to determine the effectiveness of sonochemical synthesis
      for the preparation of nano-sheets of MFUM-1(Cu) and subsequently the influence
      of particle size on physical properties such as magnetic behavior and thermal
      stability. The particles were characterized by elemental analyses, infrared
      spectroscopy (IR), scanning electron microscopy (SEM), thermogravimetric analysis
      (TGA), and powder X-ray diffraction (PXRD) analyses. The effects of parameters
      such as concentration, solvent, and reaction time on the size distribution,
      morphology, and yield of product were carefully studied. The magnetic properties
      of MFUM-1(Cu) and corresponding nano-structure were examined which indicated
      metamagnetism with strong intrachain ferromagnetic coupling versus the weak
      interchain antiferromagnetic coupling. Finally, the application of MFUM-1(Cu) in
      the separation of carbon dioxide from nitrogen and also from methane was
      theoretically investigated. High calculated selectivity of CO2 over N2 and CH4
      reveals the potential application of MFUM-1(Cu) in practical systems of gas
      separation.

PMID- 30222176
TI  - The effect of music therapy on hemodialysis patients' quality of life and
      depression symptoms.
AB  - INTRODUCTION: The sources of stress involved in chronic kidney disease (CKD) can
      lead to depressive states, directly affecting the hemodialysis patient's quality
      of life (QOL). There are few reports and studies on therapeutic interventions
      that aim to minimize depressive symptoms in these patients and an even greater
      shortage of studies using music therapy. OBJECTIVE: This study evaluated the
      effect of music therapy on QOL and depressive symptoms in hemodialysis patients.
      METHOD: This was a music therapy intervention study in which 23 patients were
      evaluated regarding QOL and depression symptoms at two distinct stages - before
      and after the intervention. Eight sessions of music therapy were conducted, with
      two weekly sessions and an average duration of 75 minutes. The intervention was
      conducted by the music therapist herself, using specific music therapy
      techniques, besides voice and guitar to conduct harmonic and rhythmic support for
      the groups' sound-music production. RESULTS: The patients showed a significant
      reduction in depression symptoms (p < 0.001) and better QOL results, with
      significant differences in the following dimensions: functional capacity (p =
      0.011), pain (p = 0.036), general health (p = 0.01), vitality (p = 0.004), mental
      health (p = 0.012), symptom and problem list (p = 0.01), and overall health (p =
      0.01). CONCLUSIONS: Intervention with music therapy constitutes an effective
      option in the treatment and prevention of depressive symptoms and improved QOL of
      HD patients.

PMID- 30222177
TI  - Renal histological findings in a patient with acute renal injury associated with
      purpura fulminans: a case report.
AB  - INTRODUCTION: Purpura fulminans (PF) is a rapid progressive thrombotic disease in
      which hemorrhagic infarction of the skin and disseminated intravascular
      coagulation (DIC) occurs. It can potentially cause acute kidney injury (AKI).
      However, there is no description in the medical literature of renal histological
      findings of PF. CASE REPORT: A 20-year-old female patient, previously healthy,
      was admitted to the emergency department (ED) with odynophagia, fever,
      generalized myalgia and anuria, which evolved with the appearance of purpuric
      plaques on the face and limbs. She required dialysis on admission. Laboratorial
      tests showed anemia, leukocytosis, thrombocytopenia, and elevation of lactic
      dehydrogenase (LDH). The purpuric lesions became bullous with ruptures and then
      necrotic and erosive, reaching the dermis, subcutaneous tissue and musculature,
      until bone exposure. There was no improvement with initial antibiotic therapy
      aimed at the treatment of meningococcemia. Thrombotic microangiopathy (TMA) and
      PF were then suspected. The patient remained in daily dialysis, requiring
      plasmapheresis. After sustained improvement of the thrombocytopenia, she
      underwent renal biopsy, which was not compatible with TMA, characterizing
      possible PF. A complete recovery of the renal function was achieved and cutaneous
      sequels were treated with grafts. CONCLUSION: When thrombotic and hemorrhagic
      phenomena overlap, obtaining a renal biopsy can be difficult. However, in the
      presented case, the biopsy allowed the exclusion of AKI caused by TMA, presenting
      for the first time, histological findings compatible with PF.

PMID- 30222178
TI  - Cognition and renal function: findings from a Brazilian population.
AB  - INTRODUCTION: The prevalence of chronic kidney disease (CKD) is increasing, with
      a potential impact in the risk of acceleration of dementia. The potential
      association between glomerular filtration rate (eGFR) and cognitive performance
      was scarcely studied. The aim of this study was to evaluate cognitive performance
      levels across different degrees of kidney function. METHODS: We analyzed 240
      outpatients in a nephrology service, classified according to eGFR: Advanced (<=
      30ml/min/1.73m2), Moderate (30,1ml/min/1.73m2 to <= 60ml/min/1.73m2), and Mild
      CKD (> 60ml/min/1.73m2). Word list memory, Semantic fluency, Mental State Mini
      Exam and Trail Making Test (TMT) were applied to evaluate cognitive performance.
      In the TMT, lower scores are associated with better cognition. In linear
      regression, cognitive function was considered as dependent variables while groups
      based on eGFR were considered explanatory variables. The group with eGFR >
      60ml/min was the reference and models were adjusted for confounding factors.
      RESULTS: In our population (n = 240) 64 patients (26.7%) were classified as
      having advanced, 98(40,8%) moderate, and 78(32,5%) mild. There was no statistical
      difference among them in MMSE or in the verbal fluency test. However, comparing
      to mild, patients with advanced CKD presented significantly worse cognitive
      performance measured by TMTA [50,8s +/- 31.1s versus 66,6s +/- 35,7s (p = 0.016)]
      and TMTB [92,7s +/- 46,2s versus 162,4s +/- 35,7s (p < 0.001)]. Significantly
      lower TMTB scores (CI95%) 33,0s (4,5-61,6s) were observed in patients with mild
      compared to advanced CKD in the multivariate analysis adjusting for age,
      education, sex, diabetes, and alcohol use. CONCLUSION: Advanced CKD is
      independently associated with poorer cognitive performance measured by an
      executive performance test compared to mild CKD.

PMID- 30222179
TI  - Retrospective review of anesthetic and analgesic regimens used in animal research
      proposals.
AB  - Pain has a profound effect on an animal's wellbeing. In Germany, researchers
      using animals have been legally required since 1972 to reduce any possible pain,
      suffering, distress or lasting harm to an absolute minimum. To evaluate how these
      provisions have been implemented in practice, an assessment of refinements to
      experimental techniques was conducted by retrospectively reviewing 684 surgical
      interventions described in 506 animal research applications that were sent to the
      German competent authorities for approval in 2010. This paper focuses on the
      efficacy of proposed anesthesia and peri- and postoperative analgesia.
      Postoperative analgesia was not proposed for 30 % of surgeries. Following 10 % of
      procedures, animals were to be given pain relieving medication if the
      investigators decided this was necessary; however, structured assessments to
      detect pain were absent. Consequences of unalleviated pain and omission of pain
      assessment techniques are discussed, and some recommendations to improve
      anesthesia and analgesia are given. The findings of this review highlight the
      need for improvement, both to fulfil legal requirements and to improve animal
      welfare. To monitor compliance with animal welfare regulations, and ensure good
      veterinary and scientific practices, education and training needs to be
      intensified. Adherence to the items listed in the PREPARE and ARRIVE guidelines
      and the Gold Standard Publication checklist (GSPC) should become legally binding.

PMID- 30222180
TI  - Genetic analyses of Astragalus sect. Humillimi (Fabaceae) resolve taxonomy and
      enable effective conservation.
AB  - PREMISE OF THE STUDY: Astragalus sect. Humillimi is distributed across the
      southwestern United States and contains two endangered taxa, A. cremnophylax var.
      cremnophylax and A. humillimus. The former was originally described from the
      South Rim of the Grand Canyon. Analysis of individuals discovered on the North
      Rim of the Grand Canyon yielded some evidence that the population represented a
      distinct species. To enable effective conservation, we clarify the group's
      taxonomy and characterize the genetic diversity of A. cremnophylax and A.
      humillimus. METHODS: We used AFLPs to genotype most species in sect. Humillimi,
      focusing on the two endangered forms. We examined patterns of genetic diversity
      using complementary analytical approaches. KEY RESULTS: Our results demonstrate
      that North Rim populations group with A. c. var. cremnophylax. We found low
      levels of genetic diversity at certain localities and strong differentiation
      among populations. Astragalus humillimus, which has suffered recent and severe
      population declines, exhibits weak differentiation among and low diversity within
      populations. CONCLUSIONS: Our results clarify the taxonomy of sect. Humillimi and
      define the boundaries of A. c. var. cremnophylax, which is shown to inhabit both
      rims of the Grand Canyon. This clarification, and detailed analysis of genetic
      variation within both endangered taxa, may advance ongoing efforts to conserve
      these taxa. Our results suggest that range-wide genetic analysis of A. humillimus
      may inform recovery strategies for this taxon.

PMID- 30222181
TI  - Hard Work, Big Changes: American Geriatrics Society Efforts to Improve Payment
      for Geriatrics Care.
AB  - This article examines the work and leadership of the American Geriatrics Society
      in making payment for services provided under new, innovative payment codes a
      reality for geriatrics healthcare professionals. We examine more than a decade of
      work spanning from a proposal to pay for comprehensive geriatric assessments in
      2003 to the multiyear effort that led to Medicare coverage for transitional care
      management (2013), chronic care management (2015, 2017), and assessment and care
      planning for cognitive impairment (2017). We review the forces that created an
      environment for change and the concurrent work of the American Medical
      Association and the Centers for Medicare and Medicaid Services that made this
      possible. We highlight opportunities seized that led to seats on crucial panels
      and legislative victories that helped us make our case for improved payment for
      geriatrics care. Finally, we address lessons learned and address opportunities
      where we are currently active. J Am Geriatr Soc 66:2059-2064, 2018.

PMID- 30222182
TI  - The presence of females induces elevated cortisol levels in an alpha male:
      Experimental evidence in chimpanzees.
AB  - OBJECTIVES: In group-living primates, it has been reported that the alpha male
      exhibits high concentrations of cortisol and testosterone in the context of
      mating competition. We investigated how the presence of females affected salivary
      cortisol and testosterone levels in males from a small captive group of
      chimpanzees (Pan troglodytes). Specifically, we assessed whether the presence of
      females resulted in a rapid increase in salivary cortisol and testosterone levels
      in the alpha male. MATERIALS AND METHODS: We compared the social behavior and
      salivary hormone concentrations of four males before and after the presentation
      of receptive females. Three times a day, we collected saliva samples, a useful
      matrix for investigating short-term hormonal changes, and measured cortisol and
      testosterone concentration by liquid chromatography-tandem mass spectrometry (LC
      MS/MS). RESULTS: The frequency of inter-male aggression increased in the presence
      of females, indicating intense competition among males. Salivary cortisol levels
      increased in all males in the presence of females; however, the increase was
      significantly more pronounced in the alpha male. We found a complex three-way
      interaction among the presence of females, sampling timings, and male dominance
      rank in the analysis of salivary testosterone. Contrary to our prediction, a post
      hoc analysis revealed that salivary testosterone levels decreased after female
      introduction and that the alpha male did not show a higher level of salivary
      testosterone. CONCLUSIONS: Our study provides experimental evidence suggesting
      that the presence of females plays a significant role in the rank-related
      variation in the cortisol levels in male chimpanzees. Furthermore, our findings
      demonstrate the usefulness of salivary hormones for detecting short-term
      physiological changes in studies of socioendocrinology.

PMID- 30222184
TI  - A quick glance at noteworthy articles in this month's issue.

PMID- 30222183
TI  - A Comprehensive Measure of the Costs of Caring for a Parent: Differences
      According to Functional Status.
AB  - Approximately 34 million family and friends provided unpaid care to individuals
      aged 50 and older in 2015. It is difficult to place a value on that time, because
      no payment is made to the caregiver, and multiplying caregiving hours by a wage
      does not account for the value of lost leisure time, implications for future
      employability and wages, or any intrinsic benefits accrued to the care provider.
      This study used a dynamic discrete choice model to estimate the costs of informal
      care provided by a daughter to her mother, including these other costs and
      benefits not typically accounted for, and compared these cost estimates for 4
      categories of the mother's functional status: doctor-diagnosed memory-related
      disease, limitations in activities of daily living (ADLs), combination of both,
      cannot be left alone for 1 hour or more. We studied women aged 40 to 70 with a
      living mother at the start of the sample period (N=3,427 adult daughters) using
      data from the Health and Retirement Study (1998-2012). The primary outcome was
      the monetized change in well-being due to caregiving, what economists call
      "welfare costs." We estimate that the median cost to the daughter's well-being of
      providing care to an elderly mother ranged from $144,302 to $201,896 over 2
      years, depending on the mother's functional status. These estimates suggest that
      informal care cost $277 billion in 2011, 20% more than estimates that account
      only for current foregone wages.

PMID- 30222188
TI  - Treating a Child With Mental Illness.
AB  - Drug treatment of attention-deficit hyperactivity disorder (ADHD) with
      stimulants, such as methylphenidate, has been widespread across the developed
      countries and is also becoming common in adults. However, this seemingly
      effective treatment is not without controversy on the evidence that supports
      their use. In addition, disparities in the frequency of its use across the world
      are tremendous. Although stimulants are one of the standard therapies for ADHD,
      autism spectrum disorder (ASD) lacks such a drug treatment. Focusing on
      neurogenetic conditions with defined genetic abnormalities, which have ASD as a
      co-existing symptom, a search for a druggable target of ASD continues.

PMID- 30222185
TI  - The compound 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces
      apoptosis via reactive oxygen species-regulated mitogen-activated protein kinase,
      protein kinase B, and signal transducer and activator of transcription 3
      signaling in human gastric cancer cells.
AB  - Hit, Lead & Candidate Discovery It is reported that 1,4-naphthoquinones and their
      derivatives have potent antitumor activity in various cancers, although their
      clinical application is limited by observed side effects. To improve the
      therapeutic efficacy of naphthoquinones in the treatment of cancer and to reduce
      side effects, we synthesized a novel naphthoquinone derivative, 2-(naphthalene-2
      thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ). In this study, we explored the
      effects of NTDMNQ on apoptosis in gastric cancer cells with a focus on reactive
      oxygen species (ROS) production. Our results demonstrated that NTDMNQ exhibited
      the cytotoxic effects on gastric cancer cells in a dose-dependent manner. NTDMNQ
      significantly induced mitochondrial-related apoptosis in AGS cells and increased
      the accumulation of ROS. However, pre-treatment with N-acetyl-L-cysteine (NAC),
      an ROS scavenger, inhibited the NTDMNQ-induced apoptosis. In addition, NTDMNQ
      increased the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) and
      decreased the phosphorylation of extracellular signal-regulated kinase (ERK),
      protein kinase B (Akt), and Signal Transducer and Activator of Transcription 3
      (STAT3); these effects were blocked by mitogen-activated protein kinase (MAPK)
      inhibitor and NAC. Taken together, the present findings indicate that NTDMNQ
      induced gastric cancer cell apoptosis via ROS-mediated regulation of the MAPK,
      Akt, and STAT3 signaling pathways. Therefore, NTDMNQ may be a potential treatment
      for gastric cancer as well as other tumor types.

PMID- 30222190
TI  - Neuroprotection of rhGLP-1 in diabetic rats with cerebral ischemia/reperfusion
      injury via regulation of oxidative stress, EAAT2, and apoptosis.
AB  - Preclinical Research & Development The purpose of the present study is to
      evaluate the neuroprotective effect of recombinant human glucagon-like peptide-1
      (rhGLP-1) as well as to explore corresponding mechanisms in diabetic rats with
      cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion
      (MCAO). Diabetes mellitus was induced by intraperitoneal injection of
      streptozotocin. The rats were pretreated with rhGLP-1 (20 MUg/kg
      intraperitoneally, thrice a day) for 14 days. Thereafter, the rats were subjected
      to MCAO 90 min/reperfusion 24 hr. At 2 and 24 hr of reperfusion, the rats were
      assessed for neurological deficits and subsequently executed for the evaluation
      of cerebral infarct volume, oxidative stress parameters, and the expression of
      excitatory amino acid transporter 2 (EAAT2) and apoptotic markers. Results
      indicate that rhGLP-1 significantly ameliorated neurological deficits and reduced
      cerebral infarct volume in diabetic MCAO rats. In addition, oxidative stress
      parameters in ischemic penumbra were significantly alleviated in rhGLP-1
      pretreated diabetic MCAO rats. rhGLP-1 significantly upregulated the ratio of Bcl
      2/Bax and EAAT2 expression and downregulated cleaved caspase-3 expression in
      ischemic penumbra of diabetic MCAO rats. Our results suggest that rhGLP-1 could
      significantly ameliorate neurological deficits and reduce cerebral infarct volume
      in diabetic MCAO rats, which may be due to the inhibition of oxidative stress and
      apoptosis and the promotion of EAAT2 expression.

PMID- 30222189
TI  - Electronic Cigarette Use and Risk of Harmful Alcohol Consumption in the U.S.
      Population.
AB  - BACKGROUND: Electronic cigarette (e-cigarette) use is an increasingly common
      method of nicotine delivery in the general population. It is well-established
      that tobacco users are at increased risk to engage in hazardous drinking and meet
      criteria for alcohol use disorder (AUD) relative to nonusers. Less is known,
      however, about the risk of harmful alcohol use among people who use e-cigarettes.
      The current study reports on the association between e-cigarette and alcohol use
      in the U.S. population using a nationally representative sample. METHODS: Data
      from 36,309 adults who participated in the National Epidemiologic Survey on
      Alcohol and Related Conditions-Wave III were included in the study. The Alcohol
      Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) measured
      past-year e-cigarette and alcohol use outcomes. Based on past-year e-cigarette
      use, respondents were categorized as nonusers, nondaily users, or daily users.
      Alcohol use outcomes were drinking quantity/frequency, binge drinking frequency,
      AUD diagnostic status, and National Institute on Alcohol Abuse and Alcoholism
      defined hazardous drinking status. RESULTS: Controlling for demographic
      characteristics, daily and nondaily e-cigarette users showed increased risk of
      harmful alcohol use compared to e-cigarette nonusers, including hazardous
      drinking (adjusted odds ratios [AORs] = 1.69; 2.48), AUD (AORs = 1.89; 2.44), and
      binge drinking frequency (AORs = 1.30 to 3.30). Nondaily e-cigarette use was
      associated with higher levels of risk than was daily use. Secondary analyses
      examined alcohol use outcomes according to participants' patterns of dual tobacco
      cigarette/e-cigarette use. These analyses confirmed that e-cigarette use
      alongside tobacco cigarette use is associated with additive risk of harmful
      alcohol consumption, particularly among nondaily users. CONCLUSIONS: E-cigarette
      users, particularly those who engage in nondaily and dual use, show elevated
      rates of harmful alcohol use. Heavy drinking may constitute a source of health
      risk among e-cigarette users.

PMID- 30222191
TI  - Arbuscular mycorrhizal phenotyping: the dos and don'ts.

PMID- 30222193
TI  - Impact of sex hormones on immune function and multiple sclerosis development.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS) affecting young people and leading to demyelination and
      neurodegeneration. The disease is clearly more common in women, in whom incidence
      has been rising. Gender differences include: earlier disease onset and more
      frequent relapses in women; and faster progression and worse outcomes in men.
      Hormone-related physiological conditions in women such as puberty, pregnancy,
      puerperium, and menopause also exert significant influence both on disease
      prevalence as well as on outcomes. Hormonal and/or genetic factors are therefore
      believed to be involved in regulating the course of disease. In this review, we
      discuss clinical evidence for the impact of sex hormones (estrogens,
      progesterone, prolactin, and testosterone) on MS and attempt to elucidate the
      hormonal and immunological mechanisms potentially underlying these changes. We
      also review current knowledge on the relationship between sex hormones and
      resident CNS cells and provide new insights in the context of MS. Understanding
      these molecular mechanisms may contribute to the development of new and safer
      treatments for both men and women.

PMID- 30222194
TI  - Electrokinetics with blood.
AB  - Microfluidics based lab-on-a-chip technology holds tremendous promises towards
      point-of-care diagnosis of diseases as well as for developing engineered devices
      aimed towards replicating the intrinsic functionalities of human bodies as
      mediated by blood vessel mimicking circulatory networks. While the analysis of
      transport of blood including its unique cellular constituents has remained to be
      the focus of many reported studies, a progressive interest on understanding the
      interplay between electric field and blood flow dynamics has paved a new way
      towards further developments from scientific engineering as well as clinical
      viewpoint. Here, we briefly outline the interconnection between electrokinetics
      and blood flow through micro-capillaries, in an effort to address several
      challenging propositions in a wide variety of applications encompassing
      biophysical transport to medical diagnostics. We first present the fundamentals
      of interaction of electric field with cellular components. In conjunction with
      the unique rheological features of blood, we show that this interaction may turn
      out to be compelling for the use of electric fields for transporting blood
      samples through microfluidic conduits. We discuss the perspectives of both direct
      current and alternating current electrokinetics in the context of blood flow. In
      addition, we provide a brief outline of the concerned theoretical developments.
      We also bring out the relevant biophysical perspectives and focus on applications
      such as blood plasma separation and separation of circulatory tumor cells.
      Finally, we attempt to provide a futuristic outlook and envisage the potential of
      combining electrokinetics with blood microcirculation towards developing
      futuristic biomimetic microdevices that can replicate a novel control mechanism
      over micro-circulatory transport in the entire connective network of human
      bodies. This may effectively pave the way towards the realization of a next
      generation medical simulation device, significantly advanced from what is
      available under the ambit of the state of art technology in the field.

PMID- 30222192
TI  - Optical probing of acetylcholine receptors on neurons in the medial habenula with
      a novel caged nicotine drug analogue.
AB  - KEY POINTS: A new caged nicotinic acetylcholine receptor (nAChR) agonist was
      developed, ABT594, which is photolysed by one- and two-photon excitation. The
      caged compound is photolysed with a quantum yield of 0.20. One-photon uncaging of
      ABT594 elicited large currents and Ca2+ transients at the soma and dendrites of
      medial habenula (MHb) neurons of mouse brain slices. Unexpectedly, uncaging of
      ABT594 also revealed highly Ca2+ -permeable nAChRs on axons of MHb neurons.
      ABSTRACT: Photochemical release of neurotransmitters has been instrumental in the
      study of their underlying receptors, with acetylcholine being the exception due
      to its inaccessibility to photochemical protection. We caged a nicotinic
      acetylcholine receptor (nAChR) agonist, ABT594, via its secondary amine
      functionality. Effective photolysis could be carried out using either one- or two
      photon excitation. Brief flashes (0.5-3.0 ms) of 410 nm light evoked large
      currents and Ca2+ transients on cell bodies and dendrites of medial habenula
      (MHb) neurons. Unexpectedly, photorelease of ABT594 also revealed nAChR-mediated
      Ca2+ signals along the axons of MHb neurons.

PMID- 30222195
TI  - Detection of T. Forsythia and other important bacteria in crestal and subcrestal
      implants with ligature-induced peri-implant infection in dogs.
AB  - BACKGROUND: The study was designed to compare peri-implant microbial colonization
      of inflamed implants placed at different levels in dogs. METHODS: Two screwed-in
      (SI) and two tapped-in (TI) conical connection implants were placed on each side
      of mandibles in six dogs respectively. Four experimental groups were constituted
      according to implant types and placement depth in one side: SI crestally (SIC),
      SI 1.5 mm subcrestally (SIS), TI crestally (TIC), and TI 1.5 mm subcrestally
      (TIS). Plaque accumulation of implants was promoted by cotton ligatures at either
      side randomly selected in each dog four weeks after abutments connection. Peri
      implant sulcular fluid (PISF) samples were collected at 4 weeks, 10 weeks, and 16
      weeks after abutment connection. Common periodontal pathogens in PISF were
      analyzed by PCR and realtime-PCR to investigate the influence of placement depth
      on microbial accumulation. The microbial results were further correlated with
      clinical parameters. RESULTS: At ligatured sides, detection rates of T. forsythia
      and P. gingivalis increased significantly in four groups. T. forsythia levels
      increased significantly from baseline in four groups at ligatured sides at 16
      weeks (p < 0.05). TIS group harbored significantly more T. forsythia than TIC at
      ligatured sides at 16 weeks (p < 0.05). At ligatured sides, probing depth was
      correlated to T. forsythia level in four groups as well as in total. CONCLUSIONS:
      Subcrestal placement could increase the peri-implant T. forsythia level at the
      early stage of peri-implantitis. The T. forsythia level in the peri-implant
      sulcus is associated with probing depth.

PMID- 30222196
TI  - Intra-strain Variability in the Effects of Temperature on UV-B Sensitivity of
      Cyanobacteria.
AB  - Stratospheric ozone depletion is mostly marked over the Antarctic and to a lesser
      extent over the Arctic, though recent reports have revealed that this also occurs
      at lower latitudes. Continued depletion of ozone in the lower stratosphere allows
      more UVR to reach the Earth's surface. Furthermore, it is projected that surface
      water temperatures will increase by between 0.2 and 2.0 degrees C by the year
      2060 and this will directly or indirectly influence algal growth. The
      interactions between environmental factors are complicated by the existence of
      different strains (ecotypes) of the same species that may respond differently. To
      understand the interactive effects of temperature and UV-B on two strains of
      Anabaena circinalis, we investigated the damaging effects of UV-B on cell numbers
      and photosynthetic characteristics and also examined the effect of temperature on
      the capacity of cells to recover from such stress. Both strains of A. circinalis
      responded differently in terms of survival, photosynthetic characteristics and
      recovery with interactions between temperature and UV-B. This could be due to the
      variations in strain-specific photoreactive mechanisms. This needs to be explored
      further including more strains and species before definitive conclusions can be
      reached about effects of global change on cyanobacteria generally.

PMID- 30222197
TI  - Efficacy of an agonist of alpha-MSH, the palmitoyl tetrapeptide-20, in hair
      pigmentation.
AB  - OBJECTIVE: Hair greying (i.e., canities) is a component of chronological ageing
      and occurs regardless of gender or ethnicity. Canities is directly linked to the
      loss of melanin and increase in oxidative stress in the hair follicle and shaft.
      To promote hair pigmentation and reduce the hair greying process, an agonist of
      alpha-melanocyte-stimulating hormone (alpha-MSH), a biomimetic peptide (palmitoyl
      tetrapeptide-20; PTP20) was developed. The aim of this study was to describe the
      effects of the designed peptide on hair greying. METHODS: Effect of the PTP20 on
      the enzymatic activity of catalase and the production of H2 O2 by Human Follicle
      Dermal Papilla Cells (HFDPC) was evaluated. Influence of PTP20 on the expression
      of melanocortin receptor-1 (MC1-R) and the production of melanin were
      investigated. Enzymatic activity of sirtuin 1 (SIRT1) after treatment with PTP20
      was also determined. Ex vivo studies using human micro-dissected hairs allowed to
      visualize the effect of PTP20 on the expression in hair follicle of catalase, TRP
      1, TRP-2, Melan-A, ASIP, and MC1-R. These investigations were completed by a
      clinical study on 15 human male volunteers suffering from premature canities.
      RESULTS: The in vitro and ex vivo studies revealed the capacity of the examined
      PTP20 peptide to enhance the expression of catalase and to decrease (30%) the
      intracellular level of H2 O2 . Moreover, PTP20 was shown to activate in vitro and
      ex vivo the melanogenesis process. In fact, an increase in the production of
      melanin was shown to be correlated with elevated expression of MC1-R, TRP-1, and
      Melan-A, and with the reduction in ASIP expression. A modulation on TRP-2 was
      also observed. The pivotal role of MC1-R was confirmed on protein expression
      analysed on volunteer's plucked hairs after 3 months of the daily application of
      lotion containing 10 ppm of PTP20 peptide. CONCLUSION: The current findings
      demonstrate the ability of the biomimetic PTP20 peptide to preserve the function
      of follicular melanocytes. The present results suggest potential cosmetic
      application of this newly designed agonist of alpha-MSH to promote hair
      pigmentation and thus, reduce the hair greying process.

PMID- 30222198
TI  - Hydrogen peroxide metabolism and functions in plants.
AB  - 1 I. Introduction 2 II. Measurement and imaging of H2 O2 2 III. H2 O2 and O2 .-
      toxicity 3 IV. Production of H2 O2 : enzymes and subcellular locations 4 V. H2 O2
      transport 9 VI. Control of H2 O2 concentration: how and where? 9 VII. Metabolic
      functions of H2 O2 11 VIII. H2 O2 signalling 11 IX. Where next? 13
      Acknowledgements 13 References 13 SUMMARY: Hydrogen peroxide (H2 O2 ) is
      produced, via superoxide and superoxide dismutase, by electron transport in
      chloroplasts and mitochondria, plasma membrane NADPH oxidases, peroxisomal
      oxidases, type III peroxidases and other apoplastic oxidases. Intracellular
      transport is facilitated by aquaporins and H2 O2 is removed by catalase,
      peroxiredoxin, glutathione peroxidase-like enzymes and ascorbate peroxidase, all
      of which have cell compartment-specific isoforms. Apoplastic H2 O2 influences
      cell expansion, development and defence by its involvement in type III peroxidase
      mediated polymer cross-linking, lignification and, possibly, cell expansion via
      H2 O2 -derived hydroxyl radicals. Excess H2 O2 triggers chloroplast and
      peroxisome autophagy and programmed cell death. The role of H2 O2 in signalling,
      for example during acclimation to stress and pathogen defence, has received much
      attention, but the signal transduction mechanisms are poorly defined. H2 O2
      oxidizes specific cysteine residues of target proteins to the sulfenic acid form
      and, similar to other organisms, this modification could initiate thiol-based
      redox relays and modify target enzymes, receptor kinases and transcription
      factors. Quantification of the sources and sinks of H2 O2 is being improved by
      the spatial and temporal resolution of genetically encoded H2 O2 sensors, such as
      HyPer and roGFP2-Orp1. These H2 O2 sensors, combined with the detection of
      specific proteins modified by H2 O2 , will allow a deeper understanding of its
      signalling roles.

PMID- 30222199
TI  - Activator-type R2R3-MYB genes induce a repressor-type R2R3-MYB gene to balance
      anthocyanin and proanthocyanidin accumulation.
AB  - Anthocyanin and proanthocyanidin (PA) accumulation is regulated by both
      myeloblastosis (MYB) activators and repressors, but little information is
      available on hierarchical interactions between the positive and negative
      regulators. Here, we report on a R2R3-MYB repressor in peach, designated PpMYB18,
      which acts as a negative regulator of anthocyanin and PA accumulation. PpMYB18
      can be activated by both anthocyanin- and PA-related MYB activators, and is
      expressed both at fruit ripening and juvenile stages when anthocyanins or PAs,
      respectively, are being synthesized. The PpMYB18 protein competes with MYB
      activators for binding to basic Helix Loop Helixes (bHLHs), which develops a fine
      tuning regulatory loop to balance PA and anthocyanin accumulation. In addition,
      the bHLH binding motif in the R3 domain and the C1 and C2 repression motifs in
      the C-terminus of PpMYB18 both confer repressive activity of PpMYB18. Our study
      also demonstrates a modifying negative feedback loop, which prevents cells from
      excess accumulation of anthocyanin and PAs, and serves as a model for balancing
      secondary metabolite accumulation at the transcriptional level.

PMID- 30222200
TI  - Size and Substitution Effect on Antimicrobial Activity of Polythiophene
      Polyelectrolyte Derivatives Under Photolysis and Dark Conditions.
AB  - Cationic polythiophenes have been shown to be potent antimicrobial compounds due
      to their ability to absorb visible light and sensitize the production of reactive
      oxygen species (ROS) as well as their ability to selectively associate with and
      damage negatively charged cell envelopes. This study demonstrates the ability of
      differentially sized imidazolium- and tertiary amine-functionalized poly(3
      hexylthiophene) (P3HT) to inactivate Gram-negative Escherichia coli and Gram
      positive Bacillus atrophaeus under photolysis and dark conditions. Flow cytometry
      viability assays are used to quantify cell death. Each compound shows high levels
      of killing at both 1 and 10 MUg mL-1 polymer concentrations for each microbial
      species after photoactivation as well as high levels of dark inactivation in many
      cases. Tertiary amine-functionalized P3HT is shown to have different killing
      patterns, shown by transmission electron microscopy, compared to the imidazolium
      functionalized derivatives.

PMID- 30222201
TI  - Structure, stability and ecological significance of natural epigenetic variation:
      a large-scale survey in Plantago lanceolata.
AB  - Within-species diversity is an important driver of ecological and evolutionary
      processes. Recent research has found that plants can harbour significant
      epigenetic diversity, but its extent, stability and ecological significance in
      natural populations is largely unexplored. We analysed genetic, epigenetic and
      phenotypic variation in a large number of natural grassland populations of
      Plantago lanceolata, covering a broad geographical and environmental range.
      Within-population diversity and among-population differentiation were calculated
      from genetic and epigenetic marker data and from measurements of phenotypic
      traits, both for plants in the field and for the F1 generation grown in a common
      environment. We found weak but significant epigenetic population structure. A
      large part of the epigenetic population differences observed in the field was
      maintained in a common environment. Epigenetic differences were consistently
      related to genetic and environmental variation, and to a lesser degree to
      phenotypic variation and land use, with more grazed populations harbouring
      greater epigenetic diversity. Our study demonstrates that epigenetic diversity
      exists in natural populations of a common grassland species, and that at least
      part of this epigenetic diversity is stable, nonrandom and related to
      environmental variation. Experimental and more detailed molecular studies are
      needed to elucidate the mechanistic basis of these observed patterns.

PMID- 30222202
TI  - Intestinal barrier integrity in patients with plaque psoriasis.
AB  - Psoriasis is a chronic inflammatory systemic disease. Growing evidence suggests
      that human homeostasis depends on a mutualistic relationship with gut bacteria
      that produce a number of biologically active compounds. Therefore, enteric
      microbiota dysbiosis with gut barrier disruption may be an important factor in
      the development of chronic inflammatory diseases. The aim of our study was to
      assess non-invasive markers of intestinal barrier integrity in patients with
      moderate to severe psoriasis. Concentrations of claudin-3 (intestinal epithelial
      tight junction structure) and intestinal fatty acid binding protein (I-FABP;
      marker of enterocyte damage) were determined in the blood of patients with
      chronic plaque psoriasis (n = 20) and healthy individuals (n = 20) using
      commercially available enzyme-linked immunoassay test kits. Claudin-3
      concentration was higher in patients with psoriasis compared with healthy control
      (median, 54.07 vs 42.36 ng/mL; P < 0.001). Patients with psoriasis also had
      elevated concentration of plasma I-FABP (median, 708.8 vs 147.1 pg/mL; P < 0.05).
      Our results support the hypothesis that dysfunction of the intestinal barrier in
      psoriasis disturbs the homeostatic equilibrium between the microbiota and immune
      system. Further studies are needed in order to develop new therapeutic
      interventions based on modulation of intestinal permeability.

PMID- 30222203
TI  - Acquisition of resistance to vemurafenib leads to interleukin-10 production
      through an aberrant activation of Akt in a melanoma cell line.
AB  - Serine/threonine-protein kinase B-Raf (BRAF) inhibitors are very effective in
      treating melanoma with BRAF mutations. BRAF inhibitors suppress aberrant growth
      of melanoma cells caused by BRAF mutations. BRAF mutations reportedly result in
      melanoma cells releasing immunosuppressive factors, and BRAF inhibitors elicit
      anti-melanoma immune responses by reducing such factors. However, immunological
      characteristics of tumor cells that acquire resistance to BRAF inhibitors remain
      unknown. Here, we compared immunological characteristics between a melanoma cell
      line and its vemurafenib-resistant subline. No differences were observed in the
      status of BRAF mutations, expression of surface molecules related to antitumor T
      cell responses or recognition by human leukocyte antigen-A*0201-matched melanoma
      specific cytotoxic T lymphocytes in a short-term co-culture assay. However,
      resistant tumor cells released high amounts of interleukin-10 depending on
      aberrant activation of Akt signaling, and dendritic cell functions were
      considerably suppressed by culture supernatants of the resistant cells. Our
      findings demonstrated a novel immunological mechanism contributing to tumor
      growth owing to drug resistance to BRAF inhibitors.

PMID- 30222205
TI  - Comparison of oxidative stress on DNA, protein and lipids in patients with
      actinic keratosis, Bowen's disease and squamous cell carcinoma.
AB  - Detailed mechanisms on the effect of oxidative stress (OS), an etiological factor
      involved in photocarcinogenesis, remain to be fully elucidated. We used
      immunohistochemical methods to study OS in the DNA, protein and lipids of
      patients with actinic keratosis (AK), Bowen's disease (BD) and squamous cell
      carcinoma (SCC). Between January 2009 and December 2014, we treated 230 patients;
      79 had AK, 61 had (BD) and 90 had cutaneous SCC; 28 healthy subjects served as
      the normal controls. OS on DNA, protein and lipids was assessed by the expression
      of 8-hydroxydeoxyguanosine (8-OHdG), dityrosine (DT) and malondialdehyde (MDA),
      respectively. 8-OHdG was significantly overexpressed in AK and BD lesions
      compared with surrounding non-lesional tissue, SCC lesions and the healthy
      controls. DT was more highly expressed in AK, BD and SCC than in the controls.
      There was no significant difference among AK, BD and SCC. The expression of MDA
      was higher in AK, BD and SCC lesions than the controls; SCC showed the highest
      expression. Our observations suggest that DNA oxidation plays an important role
      in the early stage of carcinogenesis, that protein oxidation is involved in all
      stages of carcinogenesis and that lipid oxidation is strongly implicated in the
      late stages of carcinogenesis.

PMID- 30222204
TI  - Foetal exposure to mitotane/Op'DDD: Post-natal study of four children.
AB  - OBJECTIVE: Mitotane/Op'DDD is used in the treatment of adrenocortical carcinoma
      and for other causes of hypercortisolism. Mitotane inhibits cortisol secretion
      and displays adrenolytic and antitumor actions. This compound is a metabolite of
      the pesticide and endocrine disruptor DDT (dichlorodiphenyltrichloroethane) and
      is classified among teratogenic compounds worldwide. However, little is known
      about its effects on human development. DESIGN: The outcome of four children
      exposed to mitotane during their intrauterine life was examined. PATIENTS:
      Patients having conceived while taking mitotane, or with detectable mitotane
      plasma levels, were retrospectively recruited via the French COMETE and FIRENDO
      networks. MEASUREMENTS: Mitotane in maternal plasma, adrenocortical hormones in
      children. RESULTS: Three women treated with mitotane gave birth to four children.
      During early pregnancy, all patients had detectable mitotane plasma levels (0.9,
      2.4 and 6.7 mg/L, respectively). During pregnancy, no foetal malformations were
      detected. The four exposed newborns presented at birth with apparently normal
      adrenal function and genitalia. One twin female had a low birthweight. Evaluation
      at birth and after 3 months, 2 years and 7 years of follow-up showed no
      significant neurological abnormality. Evaluation of adrenocortical functions
      showed no cortisol deficiency. CONCLUSIONS: Unexpectedly, exposure of these four
      children to mitotane during foetal life seemed to have no clear teratogenic
      effect. However, considering the sub-therapeutic mitotane concentrations used
      here, the small number of cases, and because long-term follow-up is unknown, we
      strongly advise not to take mitotane during pregnancy and still recommend
      avoiding pregnancy, at least as long as mitotane plasma levels remain detectable.

PMID- 30222206
TI  - Alopecia areata and overt thyroid diseases: A nationwide population-based study.
AB  - An association between alopecia areata (AA) and other autoimmune diseases has
      been reported. We investigated the associations between AA and overt autoimmune
      thyroid diseases. A nationwide, population-based, cross-sectional study was
      performed using the Korea National Health Insurance claims database. We defined
      patients with AA as those whose records showed at least four physician contacts
      in which AA, alopecia totalis (AT) or alopecia universalis (AU) was the principal
      diagnosis. We also established an age- and sex-matched control group without AA.
      In a subgroup analysis, patients with AT or AU were classified into the severe AA
      group, and the remainder were classified into the mild to moderate AA group.
      Patients with AA were at an increased risk of Graves' disease (odds ratio [OR],
      1.415; 95% confidence interval [CI], 1.317-1.520) and Hashimoto thyroiditis (OR,
      1.157; 95% CI, 1.081-1.237), and the associations were stronger in the severe AA
      group (Graves' disease: OR, 1.714; 95% CI, 1.387-2.118; Hashimoto thyroiditis:
      OR, 1.398; 95% CI, 1.137-1.719). In conclusion, AA was significantly associated
      with overt autoimmune thyroid diseases. Furthermore, the risk was much higher in
      the severe AA group.

PMID- 30222207
TI  - An observational study of environmental exposures, airway cytology, and
      performance in racing thoroughbreds.
AB  - BACKGROUND: Mild equine asthma is presumed to arise in response to environmental
      exposures but the relative impact of differing inflammatory phenotypes upon
      performance are largely unexplored. HYPOTHESES: Airway inflammation negatively
      affects performance and cytological phenotype varies with environmental exposure.
      ANIMALS: Thoroughbred racehorses in active training and racing. METHODS:
      Thoroughbreds were recruited 24-48 hours before racing. Each horse was eligible
      for re-enrollment with each race entry. Within one hour of race completion,
      physical examination, respiratory endoscopy, and BAL were performed. Respirable
      and inhalable dust, respirable endotoxin, and respirable beta-glucan exposures
      were measured at the breathing zone within one week after racing. Controlling for
      age, trainer, and pulmonary hemorrhage, the relationship between performance,
      bronchoalveolar lavage fluid (BALF) cytology, and measures of exposure were
      modeled. RESULTS: Performance and BALF data were collected on 64 individual
      horses from 8 stables for a total of 98 race performances and 79 dust exposure
      assessments. Evidence of mild equine asthma was found in 80% (78/98) of BALF
      samples from 52/64 horses. For each percent increase in BALF mast cell and
      neutrophil proportions, speed figures were reduced by 2.9 (P = .012) and 1.4 (P =
      .046) points, respectively. Respirable dust concentration was associated with
      BALF neutrophil proportions (P = .015). Bronchoalveolar lavage fluid mast cell
      proportions were only associated with respirable beta-glucan exposures (P =
      .030). CONCLUSIONS AND CLINICAL IMPORTANCE: Mild equine asthma is common in
      racing horses and negatively impacts performance. The data support that
      respirable, rather than inhalable, dust exposure measures are pertinent to equine
      airway health.

PMID- 30222208
TI  - Eccentric cycling is more efficient in reducing fat mass than concentric cycling
      in adolescents with obesity.
AB  - The benefits of eccentric (ECC) training on fat mass (FM) remain underexplored.
      We hypothesized that in obese adolescents, ECC cycling training is more efficient
      for decreasing whole-body FM percentage compared to concentric (CON) performed at
      the same oxygen consumption (VO2 ). Twenty-four adolescents aged 13.4 +/- 1.3
      years (BMI > 90th percentile) were randomized to ECC or CON. They performed three
      cyclo-ergometer sessions per week (30 min per session) for 12 weeks: two
      habituation, 5 at 50% VO2peak , and 5 at 70% VO2peak . Anthropometric
      measurements, body composition, maximal incremental CON tests, strength tests,
      and blood samples were assessed pre- and post-training. Whole-body FM percentage
      decreased significantly after compared to pretraining in both groups, though to a
      larger extent in the ECC group (ECC: -10% vs CON: -4.2%, P < 0.05). Whole-body
      lean mass (LM) percentage increased significantly in both groups after compared
      to pretraining, with a greater increase in the ECC group (ECC: 3.8% vs CON: 1.5%,
      P <0.05). The improvements in leg FM and LM percentages were greater in the ECC
      group (-6.5% and 3.0%, P = 0.01 and P < 0.01). Quadriceps isometric and
      isokinetic ECC strength increased significantly more in the ECC group (28.3% and
      21.3%, P < 0.05). Both groups showed similar significant VO2peak improvement
      (ECC: 15.4% vs CON: 10.3%). The decrease in homeostasis model assessment of
      insulin resistance index was significant in the ECC group (-19.9%). In
      conclusion, although both ECC and CON cycling trainings are efficient to decrease
      FM, ECC induces greater FM reduction, strength gains, and insulin resistance
      improvements and represents an optimal modality to recommend for obese
      adolescents.

PMID- 30222210
TI  - The identification of autoantigens in mucous membrane pemphigoid using
      immortalized oral mucosal keratinocytes.
AB  - BACKGROUND: Mucous membrane pemphigoid (MMP) is a rare chronic autoimmune
      subepithelial blistering disorder, targeting multiple basement membrane zone
      (BMZ) proteins including collagen XVII (COL17). Circulating autoantibodies of MMP
      are often undetected due to their lower titers. The oral mucosa is a valuable
      substrate for the detection of autoantibodies in MMP patients. However, obtaining
      normal human oral mucosa is more difficult than obtaining normal human skin. We
      established immortalized normal human oral mucosal keratinocytes (OMKs) and
      performed immunoblotting using immortalized OMK lysate for detecting autoantigens
      in MMP. METHODS: Immortalized OMKs were generated from primary OMKs using E6/E7
      proteins of HPV. We compared the protein expression levels of major BMZ proteins
      between primary OMKs and immortalized OMKs. We performed immunoblotting to detect
      autoantigens using cell lysates from immortalized OMKs in 30 MMP patients.
      RESULTS: There were no significant differences between primary OMKs and
      immortalized OMKs in terms of protein expression levels of the BMZ proteins,
      including COL17, laminin 332, integrin alpha6/beta4, collagen VII, and collagen
      IV. Cell lysates of immortalized OMKs effectively identified MMP autoantigens in
      60% (18/30) of MMP sera. We found an interesting case of MMP whose autoantibodies
      preferentially reacted to the 120-kD protein that is an ectodomain of COL17.
      CONCLUSION: We demonstrated that a cell lysate of immortalized OMKs is a reliable
      substrate for the detection of MMP autoantigens. This newly developed
      immunoblotting analysis method promises to contribute to the diagnosis of MMP.

PMID- 30222211
TI  - Resolution of isoborneol and its isomers by GC/MS to identify "synthetic" and
      "semi-synthetic" borneol products.
AB  - Borneol is a plant terpene commonly used in traditional Chinese medicine.
      Optically pure (+)-borneol and (-)-borneol can be obtained by extraction from the
      plants Dipterocarpaceae and Blumea balsamifera, respectively. "Synthetic borneol"
      is obtained from the reduction of (+/-)-camphor to lead to four different
      stereoisomers: (+)-isoborneol, (-)-isoborneol, (+)-borneol, and (-)-borneol. In
      contrast, "semi-synthetic borneol" is produced from the reduction of natural
      camphor, (+)-camphor, to afford two isomers: (-)-isoborneol and (+)-borneol. We
      established a convenient method to identify them by treating the four
      stereoisomers with two chiral reagents, (R)-(+)-alpha-methoxy-alpha
      trifluoromethylphenylacetyl chloride ((R)-(+)-MTPA-Cl) and (1S)-(-)- camphanic
      chloride. The resulting derivatives from the above mentioned method were analyzed
      by gas chromatography. The enantiomers of (+)- and (-)-isoborneol were
      successfully separated from (+)- and (-)-borneol isomers in this study to make
      this a useful method in the identification of "synthetic" and "semi-synthetic"
      borneols. Furthermore, we also examined five different commercial borneols.
      During this course, a novel and unprecedented partial epimerization from
      isoborneol-camphanic ester to borneol-camphanic ester was observed. However, this
      phenomenon did not occur in isoborneol-MTPA esters epimerization to borneol-MTPA
      case under the same conditions. The DFT calculation of activation energies for
      both reactions was in a good agreement with the results obtained from GC
      analysis.

PMID- 30222212
TI  - Variations in maternal adenylate cyclase genes are associated with congenital
      Zika syndrome in a cohort from Northeast, Brazil.
AB  - BACKGROUND: Vertical transmission of Zika virus (ZIKV) is associated with
      congenital malformations but the mechanism of pathogenesis remains unclear.
      Although host genetics appear to play a role, no genetic association study has
      yet been performed to evaluate this question. In order to investigate if maternal
      genetic variation is associated with Congenital Zika Syndrome (CZS), we conducted
      a case-control study in a cohort of Brazilian women infected with ZIKV during
      pregnancy. METHODS: A total of 100 women who reported symptoms of zika during
      pregnancy were enrolled and tested for ZIKV. Among 52 women positive for ZIKV
      infection, 28 were classified as cases and 24 as controls based on the presence
      or absence of CZS in their infants. Variations in the coding region of 205
      candidate genes involved in cAMP signaling or immune response were assessed by
      high throughput sequencing and tested for association with development of CZS.
      RESULTS: From the 817 single nucleotide variations (SNVs) included in association
      analyses, 22 SNVs in 17 genes were associated with CZS under an additive model
      (alpha = 0.05). Variations c.319T>C (rs11676272) and c.1297G>A, located at ADCY3
      and ADCY7 genes showed the most prominent effect. The association of ADCY3 and
      ADCY7 genes was confirmed using a Sequence Kernel Association Test to assess the
      joint effect of common and rare variations, and results were statistically
      significant after adjustment for multiple comparisons (P < 0.002). CONCLUSION:
      These results suggest that maternal ADCY genes contribute to ZIKV pathogenicity
      and influence the outcome of CZS, being promising candidates for further
      replication studies and functional analysis.

PMID- 30222213
TI  - Stimuli-Responsive Properties of Aggregation-Induced-Emission Compounds
      Containing a 9,10-Distyrylanthracene Moiety.
AB  - Two 9,10-distyrylanthracene-based luminophores exhibiting aggregation-induced
      emission and stimuli-responsive properties were synthesized. Seven- or five-color
      luminescence switching based on a single organic molecule was achieved for the
      first time. These phase transitions can be induced by physical stimuli such as
      grinding by mortar and pestle, heating, and exposure to the vapors of organic
      solvents. Moreover, a strategy for the design of new mechanoresponsive materials
      with pi-conjugated luminophores is proposed.

PMID- 30222209
TI  - Clinical utility of currently available biomarkers in inflammatory enteropathies
      of dogs.
AB  - Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that
      are characterized by chronic persistent or recurrent signs of gastrointestinal
      disease and histologic evidence of mucosal inflammation. These CIEs are
      classified as either food-responsive, antibiotic-responsive, or immunosuppressant
      responsive enteropathy. Patients not clinically responding to immunomodulatory
      treatment are grouped as nonresponsive enteropathy and dogs with intestinal
      protein loss as protein-losing enteropathy. Disease-independent clinical scoring
      systems were established in dogs for assessment of clinical disease severity and
      patient monitoring during treatment. Histopathologic and routine
      clinicopathologic findings are usually not able to distinguish the subgroups of
      CIE. Treatment trials are often lengthy and further diagnostic tests are usually
      at least minimally invasive. Biomarkers that can aid in defining the presence of
      disease, site of origin, severity of the disease process, response to treatment,
      or a combination of these would be clinically useful in dogs with CIE. This
      article summarizes the following biomarkers that have been evaluated in dogs with
      CIE during the last decade, and critically evaluates their potential clinical
      utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid,
      folate, alpha1 -proteinase inhibitor, immunoglobulin A), biochemical biomarkers
      (C-reactive protein, perinuclear anti-neutrophilic cytoplasmic antibodies, 3
      bromotyrosine, N-methylhistamine, calprotectin, S100A12, soluble receptor of
      advanced glycation end products, cytokines and chemokines, alkaline phosphatase),
      microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic
      biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene
      expression changes), and cellular biomarkers (regulatory T cells). In addition,
      important performance criteria of diagnostic tests are briefly reviewed.

PMID- 30222214
TI  - Metallacarboranes on the Road to Anticancer Therapies: Cellular Uptake, DNA
      Interaction, and Biological Evaluation of Cobaltabisdicarbollide [COSAN].
AB  - After uptake by U87 MG and A375 cancer cells, cobaltabisdicarbollide [COSAN]-
      distributes between membrane and nucleus and presents no relevant cytotoxicity
      against both cell lines even for long incubation times. The cytotoxicity of
      Na[COSAN] was also tested towards one normal cell line, the V79 fibroblasts, in
      order to ascertain the noncytotoxic profile of the compound. As the cell's
      nucleus contains DNA, the interaction between [COSAN]- and double-stranded calf
      thymus DNA (CT-dsDNA) has been investigated. There is a strong interaction
      between both molecules forming a nanohybrid CT-dsDNA-[COSAN] biomaterial, which
      was fully characterized. Moreover, Na[COSAN] shows characteristic redox peaks
      ascribed to the oxidation/reduction of Co3+/2+ at a formal potential of -1.444 V
      and it can be accumulated at a surface-immobilized DNA layer of glassy carbon
      electrodes. The equilibrium surface-binding constants (Kox /Kred ), which confirm
      that [COSAN]- interacts with DNA by an intercalative or electrostatic mode,
      depending on the ionic strength of the solution, were estimated. In addition,
      high binding affinity of Na[COSAN] to proteins was observed by 11 B{1 H} NMR and
      confirmed in vivo. Finally, biodistribution studies of [COSAN]- in normal mice
      were run. After administration, Na[COSAN] was distributed into many organs but
      mainly accumulated in the reticuloendothelial system (RES), including liver and
      spleen. After 1 h, the formation of aggregates by plasma protein interaction
      plays a role in the biodistribution profile; the aggregates accumulate mostly in
      the lungs. Na[COSAN], which displays low toxicity and high uptake by relevant
      cancer cells accumulating boron within the nucleus, could act as a suitable
      compound for further developments as boron neutron capture therapy (BNCT) agents.

PMID- 30222215
TI  - Interactions of C-F Bonds with Hydridoboranes: Reduction, Borylation and Friedel
      Crafts Alkylation.
AB  - The stoichiometric reactions of the alkylfluorides 1-fluoroadamantane (Ad-F),
      fluorocyclohexane (Cy-F), 1-fluoropentane (Pent-F) and benzyl fluorides with
      secondary boranes pinacolborane (HBpin), catecholborane (HBcat), 9
      borabicyclo(3.3.1)nonane (9-BBN) and Piers' borane (HB(C6 F5 )2 ) are described.
      While HBcat, 9-BBN and HB(C6 F5 )2 reduce Ad-F to Ad-H, the latter borane was
      shown to react with secondary and primary fluoroalkanes, affording C-F
      borylation, while benzyl fluorides undergo Friedel-Crafts chemistry.

PMID- 30222216
TI  - N-Type Organic Thermoelectrics of Donor-Acceptor Copolymers: Improved Power
      Factor by Molecular Tailoring of the Density of States.
AB  - It is demonstrated that the n-type thermoelectric performance of donor-acceptor
      (D-A) copolymers can be enhanced by a factor of >1000 by tailoring the density of
      states (DOS). The DOS distribution is tailored by embedding sp2 -nitrogen atoms
      into the donor moiety of the D-A backbone. Consequently, an electrical
      conductivity of 1.8 S cm-1 and a power factor of 4.5 uW m-1 K-2 are achieved.
      Interestingly, an unusual sign switching (from negative to positive) of the
      Seebeck coefficient of the unmodified D-A copolymer at moderately high dopant
      loading is observed. A direct measurement of the DOS shows that the DOS
      distributions become less broad upon modifying the backbone in both pristine and
      doped states. Additionally, doping-induced charge transfer complexes (CTC)
      states, which are energetically located below the neutral band, are observed in
      DOS of the doped unmodified D-A copolymer. It is proposed that charge transport
      through these CTC states is responsible for the positive Seebeck coefficients in
      this n-doped system. This is supported by numerical simulation and temperature
      dependence of Seebeck coefficient. The work provides a unique insight into the
      fundamental understanding of molecular doping and sheds light on designing
      efficient n-type OTE materials from a perspective of tailoring the DOS.

PMID- 30222217
TI  - Entrapment of THF-Stabilized Iridacyclic IrIII Silylenes from Double H-Si Bond
      Activation and H2 Elimination.
AB  - The reaction of H3 SiR (R=Ph, nBu) with cationic eta5 -C5 Me5 - (Cp*) and
      benzo[h]quinolinyl-based iridacycle [1 b]+ gives rise to new [(IrH)->SiRH2 ]+
      adducts. In the presence of THF these adducts readily undergo elimination of H2
      gas at subambient temperature to form THF-stabilized metallacyclic IrIII silylene
      complexes, which were characterized in situ by NMR spectroscopy, trapped in
      minute amounts by reactive crystallization, and structurally characterized by
      XRD. Theoretical investigations (static DFT-D reaction-energy profiling, ETS
      NOCV) support the promoting role of THF in the H2 elimination step and the
      consolidation of the Ir-to-Si interaction in the spontaneous (DeltaG<0) formation
      of Ir silylenes in the presence of THF. Mechanistic insights indicate that the Ir
      silylene species arising from the [1 b]+ /phenylsilane system are relevant
      catalytic species in the hydrodefluorination of fluoroalkanes.

PMID- 30222218
TI  - Interfacial Defect Vibrations Enhance Thermal Transport in Amorphous Multilayers
      with Ultrahigh Thermal Boundary Conductance.
AB  - The role of interfacial nonidealities and disorder on thermal transport across
      interfaces is traditionally assumed to add resistance to heat transfer,
      decreasing the thermal boundary conductance (TBC). However, recent computational
      studies have suggested that interfacial defects can enhance this thermal boundary
      conductance through the emergence of unique vibrational modes intrinsic to the
      material interface and defect atoms, a finding that contradicts traditional
      theory and conventional understanding. By manipulating the local heat flux of
      atomic vibrations that comprise these interfacial modes, in principle, the TBC
      can be increased. In this work, experimental evidence is provided that
      interfacial defects can enhance the TBC across interfaces through the emergence
      of unique high-frequency vibrational modes that arise from atomic mass defects at
      the interface with relatively small masses. Ultrahigh TBC is demonstrated at
      amorphous SiOC:H/SiC:H interfaces, approaching 1 GW m-2 K-1 and are further
      increased through the introduction of nitrogen defects. The fact that disordered
      interfaces can exhibit such high conductances, which can be further increased
      with additional defects, offers a unique direction to manipulate heat transfer
      across materials with high densities of interfaces by controlling and enhancing
      interfacial thermal transport.

PMID- 30222219
TI  - From Photoinduced to Dark Cytotoxicity through an Octahedral Cluster Hydrolysis.
AB  - Octahedral molybdenum and tungsten clusters have potential biological
      applications in photodynamic therapy and bioimaging. However, poor solubility and
      hydrolysis stability of these compounds hinder their application. The first water
      soluble photoluminescent octahedral tungsten cluster [{W6 I8 }(DMSO)6 ](NO3 )4
      was synthesised and demonstrated to be at least one order of magnitude more
      stable towards hydrolysis than its molybdenum analogue. Biological studies of the
      compound on larynx carcinoma cells suggest that it has a significant photoinduced
      toxicity, while the dark toxicity increases with the increase of the degree of
      hydrolysis. The increase of the dark toxicity is associated with the in situ
      generation of nanoparticles that clog up the cisternae of rough endoplasmic
      reticulum.

PMID- 30222220
TI  - The Effects of Doping Density and Temperature on the Optoelectronic Properties of
      Formamidinium Tin Triiodide Thin Films.
AB  - Optoelectronic properties are unraveled for formamidinium tin triiodide (FASnI3 )
      thin films, whose background hole doping density is varied through SnF2 addition
      during film fabrication. Monomolecular charge-carrier recombination exhibits both
      a dopant-mediated part that grows linearly with hole doping density and remnant
      contributions that remain under tin-enriched processing conditions. At hole
      densities near 1020 cm-3 , a strong Burstein-Moss effect increases absorption
      onset energies by ~300 meV beyond the bandgap energy of undoped FASnI3 (shown to
      be 1.2 eV at 5 K and 1.35 eV at room temperature). At very high doping densities
      (1020 cm-3 ), temperature-dependent measurements indicate that the effective
      charge-carrier mobility is suppressed through scattering with ionized dopants.
      Once the background hole concentration is nearer 1019 cm-3 and below, the charge
      carrier mobility increases with decreasing temperature according to ~T-1.2 ,
      suggesting that it is limited mostly by intrinsic interactions with lattice
      vibrations. For the lowest doping concentration of 7.2 * 1018 cm-3 , charge
      carrier mobilities reach a value of 67 cm2 V-1 s-1 at room temperature and 470
      cm2 V-1 s-1 at 50 K. Intraexcitonic transitions observed in the THz-frequency
      photoconductivity spectra at 5 K reveal an exciton binding energy of only 3.1 meV
      for FASnI3 , in agreement with the low bandgap energy exhibited by this
      perovskite.

PMID- 30222221
TI  - Tuning Ion Complexing To Rapidly Prepare Hollow Ag-Pt Nanowires with High
      Activity toward the Methanol Oxidization Reaction.
AB  - Hollow Pt-based nanowires (NWs) have important applications in catalysis. Their
      preparation often involves a two-step process in which M (M=Ag, Pd, Co, Ni) NWs
      are prepared and subsequently subjected to galvanic reaction in solution
      containing a Pt precursor. It is challenging to achieve a simple one-step
      preparation, because the redox potential of PtIV /Pt or PtII /Pt to Pt is high,
      and therefore, Pt atoms always form first. This work demonstrates that an
      appropriate pH can decrease the redox potential of PtIV /Pt and allows the one
      step preparation of high-quality hollow Pt-Ag NWs rapidly (10 min). Moreover, it
      is easy to realize large-scale preparation with this method. The NW composition
      can be adjusted readily to optimize their performance in the electrocatalytic
      methanol oxidization reaction (MOR). Compared with commercial Pt/C, NWs with
      appropriate Ag/Pt ratios exhibit high stability, activity, and CO tolerance
      ability.

PMID- 30222224
TI  - Reporting matters: Brain mapping with transcranial magnetic stimulation.

PMID- 30222222
TI  - Total antioxidant capacity and protein peroxidation intensity in seminal plasma
      of infertile and fertile dogs.
AB  - The aim of this study was to evaluate the total antioxidant capacity and protein
      peroxidation intensity in seminal plasma of infertile and fertile dogs. The study
      was conducted on 10 infertile and 10 fertile dogs of various breeds. Infertility
      was defined as conception failure at least three matings with different bitches.
      Semen was collected by manual manipulation. The sperm concentration and motility
      parameters were evaluated using CASA Hamilton Thorne, Vers. IVOS 12.3. The
      morphology of spermatozoa and the percentage of live and dead sperm cells were
      assessed microscopically, total antioxidant capacity and the content of SH-groups
      in seminal plasma were determined spectrophotometrically, the contents of protein
      peroxidation markers in seminal plasma, bityrosine and formylokinurenine, were
      determined using spectrofluorimetric methods. Sperm concentration and total sperm
      count were significantly (p < 0.05) lower in infertile dogs than in fertile dogs
      (99.92 +/- 3 0.05 * 106 /ml vs. 282.07 +/- 48.27 * 106 /ml; 214.19 +/- 114.74 *
      106 vs. 747.57 +/- 210.94 * 106 , respectively). The percentage of spermatozoa
      with normal morphology and the most determined motility parameters differed
      significantly (p < 0.05) between both groups. The mean values of total
      antioxidant capacity in the seminal plasma were significantly (p < 0.05) lower
      (19.95 +/- 20.94 vs. 25.66 +/- 23.18 umol/g protein), whereas the mean contents
      of bityrosine and formylokinurenine in seminal plasma were significantly (p <
      0.05) higher in infertile dogs than in fertile dogs (3.71 +/- 4.83 ug/mg protein
      vs. 1.55 +/- 2.00 ug/mg protein and 0.37 +/- 0.45 ug/mg protein vs. 0.14 +/- 0.08
      ug/mg protein, respectively). In conclusion, the obtained results suggest that
      the poor semen quality and infertility in dogs could be associated with lowered
      total antioxidant capacity and increased protein peroxidation in seminal plasma
      as a consequence of oxidative stress.

PMID- 30222223
TI  - Ultrasonic Exfoliation of Hydrophobic and Hydrophilic Metal-Organic Frameworks To
      Form Nanosheets.
AB  - The modular structure of metal-organic framework nanosheets (MONs) provides a
      convenient route to creating two-dimensional materials with readily tuneable
      surface properties. Here, the liquid exfoliation of two closely related layered
      metal-organic frameworks functionalised with either methoxy-propyl (1) or pentyl
      (2) pendent groups intended to bestow either hydrophilic or hydrophobic character
      to the resulting nanosheets is reported. Exfoliation of the two materials in a
      range of different solvents highlighted significant differences in their
      dispersion properties, as well as their molecular and nanoscopic structures.
      Exchange or loss of solvent was found to occur at the labile axial position of
      the paddle-wheel based MONs and DFT calculations indicated that intramolecular
      coordination by the oxygen of the methoxy-propyl pendant groups may take place.
      The nanoscopic dimensions of the MONs were further tuned by varying the
      exfoliation conditions and through "liquid cascade centrifugation". Aqueous
      suspensions of the nanosheets were used as sensors to detect aromatic
      heterocycles with clear differences in binding behaviour observed and quantified.

PMID- 30222225
TI  - Disentangling protist communities identified from DNA and RNA surveys in the
      Pearl River-South China Sea Continuum during the wet and dry seasons.
AB  - Little is known about the mechanisms that regulate the assembly of microbial
      communities in the river-sea continuum. Here, we performed HiSeq paired-end
      sequencing of the V4 region of 18S rRNA gene, using both DNA and RNA extracts, to
      identify protist communities in the surface and bottom water layers along a
      transect of the Pearl River-South China Sea Continuum (PSC) during the wet
      (summer) and dry (winter) seasons. We found that during the summer but not during
      the winter, protist communities, identified from their DNA or RNA signatures,
      could be better explained by mass effects and species sorting, respectively.
      Moreover, protist diversity in the DNA and RNA surveys exhibited similar trends
      along the transect, that is, a linear upstream-to-downstream decrease during the
      summer and a weakly U-shaped curve during the winter. In contrast, the taxonomic
      compositions in the DNA- and RNA-derived communities were remarkably different
      during either the summer or the winter. In summary, the results of our DNA and
      RNA surveys revealed the temporal assembly of protist communities in the PSC,
      which suggests that protist diversity and composition are highly responsive to
      the hydrographic conditions of the river-sea continuum.

PMID- 30222227
TI  - A Social Emergency Medicine Approach to the Implementation of Sexual and
      Reproductive Health Interventions in the Emergency Department.

PMID- 30222226
TI  - Species-complex diversification and host-plant associations in Bemisia tabaci: A
      plant-defence, detoxification perspective revealed by RNA-Seq analyses.
AB  - Insect-plant associations and their role in diversification are mostly studied in
      specialists. Here, we aimed to identify macroevolution patterns in the
      relationships between generalists and their host plants that have the potential
      to promote diversification. We focused on the Bemisia tabaci species complex
      containing more than 35 cryptic species. Mechanisms for explaining this
      impressive diversification have focused so far on allopatric forces that assume a
      common, broad, host range. We conducted a literature survey which indicated that
      species in the complex differ in their host range, with only few showing a truly
      broad one. We then selected six species, representing different phylogenetic
      groups and documented host ranges. We tested whether differences in the species
      expression profiles of detoxification genes are shaped more by their phylogenetic
      relationships or by their ability to successfully utilize multiple hosts,
      including novel ones. Performance assays divided the six species into two groups
      of three, one showing higher performance on various hosts than the other (the
      lower performance group). The same grouping pattern appeared when the species
      were clustered according to their expression profiles. Only species placed in the
      lower performance group showed a tendency to lower the expression of multiple
      genes. Taken together, these findings bring evidence for the existence of a
      common detoxification "machinery," shared between species that can perform well
      on multiple hosts. We raise the possibility that this "machinery" might have
      played a passive role in the diversification of the complex, by allowing
      successful migration to new/novel environments, leading, in some cases, to
      fragmentation and speciation.

PMID- 30222228
TI  - Apparent inbreeding preference despite inbreeding depression in the American
      crow.
AB  - Although matings between relatives can have negative effects on offspring
      fitness, apparent inbreeding preference has been reported in a growing number of
      systems, including those with documented inbreeding depression. Here, we examined
      evidence for inbreeding depression and inbreeding preference in two populations
      (Clinton, New York and Davis, California, USA) of the cooperatively breeding
      American crow (Corvus brachyrhynchos). We then compared observed inbreeding
      strategies with theoretical expectations for optimal, adaptive levels of
      inbreeding, given the inclusive fitness benefits and population-specific
      magnitude of inbreeding depression. We found that low heterozygosity at a panel
      of 33 microsatellite markers was associated with low survival probability
      (fledging success) and low white blood cell counts among offspring in both
      populations. Despite these costs, our data were more consistent with inbreeding
      preference than avoidance: the observed heterozygosity among 396 sampled crow
      offspring was significantly lower than expected if local adults were mating by
      random chance. This pattern was consistent across a range of spatial scales in
      both populations. Theoretically adaptive levels of inbreeding, given the
      magnitude of inbreeding depression, were predicted to be very low in the
      California population, whereas complete disassociative mating was predicted in
      the New York population. Sexual conflict might have contributed to the apparent
      absence of inbreeding avoidance in crows. These data add to an increasing number
      of examples of an "inbreeding paradox," where inbreeding appears to be preferred
      despite inbreeding depression. This article is protected by copyright. All rights
      reserved.

PMID- 30222229
TI  - Does adaptation to different diets result in assortative mating? Ambiguous
      results from experiments on Drosophila.
AB  - The emergence of behavioural isolation between populations under divergent
      selection can be crucial for ecological speciation, but the mechanisms underlying
      such isolation are poorly understood. Several experimental evolution studies have
      shown that positive assortative mating (preference for similar mates) can arise
      rapidly in Drosophila laboratory populations reared in different stressful
      conditions, while other studies failed to confirm this effect. Here, we present
      the results of an evolution experiment in which outbred lines of Drosophila
      melanogaster were reared for 1-2 years on one of the three different diets
      (standard, starch based or high salt). We show that nonrandom mating arose in
      some, but not all lines, and that the manifestations and possible interpretations
      of this nonrandomness depend strongly on the type of tests used to assess mating
      preferences. More specifically, multiple-choice four-fly tests revealed positive
      assortative mating (prevalence of homogamic matings) in some starch-adapted and
      salt-adapted lines when paired with a control line reared on the standard diet,
      but competitive three-fly tests rather revealed competitive advantage of control
      males and females over the flies reared on stressful diets. The results imply
      that divergent adaptation can result in differences in mating propensity or
      competitive ability, which, in turn, may either facilitate or hamper speciation
      depending on the relative frequency of high- vs. low-competition settings in
      natural habitats of the diverging populations. The results also emphasize the
      importance of using diverse tests for assessing mating structure in natural and
      laboratory populations.

PMID- 30222230
TI  - l-Asparaginase: aspiring for better outcomes in endometrial cancer.

PMID- 30222231
TI  - The Action of the Hexokinase Inhibitor 2-deoxy-d-glucose on Cryptosporidium
      parvum and the Discovery of Activities against the Parasite Hexokinase from
      Marketed Drugs.
AB  - Cryptosporidium parvum is one of the major species causing mild to severe
      cryptosporidiosis in humans and animals. We have previously observed that 2-deoxy
      d-glucose (2DG) could inhibit both the enzyme activity of C. parvum hexokinase
      (CpHK) and the parasite growth in vitro. However, the action and fate of 2DG in
      C. parvum was not fully investigated. In the present study, we showed that,
      although 2DG could be phosphorylated by CpHK to form 2DG-6-phosphate (2DG6P), the
      anti-cryptosporidial activity of 2DG was mainly attributed to the action of 2DG
      on CpHK, rather than the action of 2DG or 2DG6P on the downstream enzyme glucose
      6-phosphate isomerase (CpGPI) nor 2DG6P on CpHK. These observations further
      supported the hypothesis that CpHK could serve as a drug target in the parasite.
      We also screened 1,200 small molecules consisting of marketed drugs against CpHK,
      from which four drugs were identified as CpHK inhibitors with micromolar level of
      anti-cryptospordial activities at concentrations nontoxic to the host cells (i.e.
      hexachlorphene, thimerosal, alexidine dihydrochloride, and ebselen with EC50  =
      0.53, 1.77, 8.1 and 165 MUM, respectively). The anti-CpHK activity of the four
      existing drugs provided us new reagents for studying the enzyme properties of the
      parasite hexokinase.

PMID- 30222232
TI  - Accuracy of Dementia Screening Instruments in Emergency Medicine: A Diagnostic
      Meta-analysis.
AB  - BACKGROUND: Dementia is underrecognized in older adult emergency department (ED)
      patients, which threatens operational efficiency, diagnostic accuracy, and
      patient satisfaction. The Society for Academic Emergency Medicine geriatric ED
      guidelines advocate dementia screening using validated instruments. OBJECTIVES:
      The objective was to perform a systematic review and meta-analysis of the
      diagnostic accuracy of sufficiently brief screening instruments for dementia in
      geriatric ED patients. A secondary objective was to define an evidence-based
      pretest probability of dementia based on published research and then estimate
      disease thresholds at which dementia screening is most appropriate. This
      systematic review was registered with PROSPERO (CRD42017074855). METHODS: PubMed,
      EMBASE, CINAHL, CENTRAL, DARE, and SCOPUS were searched. Studies in which ED
      patients ages 65 years or older for dementia were included if sufficient details
      to reconstruct 2 * 2 tables were reported. QUADAS-2 was used to assess study
      quality with meta-analysis reported if more than one study evaluated the same
      instrument against the same reference standard. Outcomes were sensitivity,
      specificity, and positive and negative likelihood ratios (LR+ and LR-). To
      identify test and treatment thresholds, we employed the Pauker-Kassirer method.
      RESULTS: A total of 1,616 publications were identified, of which 16 underwent
      full text-review; nine studies were included with a weighted average dementia
      prevalence of 31% (range, 12%-43%). Eight studies used the Mini Mental Status
      Examination (MMSE) as the reference standard and the other study used the MMSE in
      conjunction with a geriatrician's neurocognitive evaluation. Blinding to the
      index test and/or reference standard was inadequate in four studies. Eight
      instruments were evaluated in 2,423 patients across four countries in Europe and
      North America. The Abbreviated Mental Test (AMT-4) most accurately ruled in
      dementia (LR+ = 7.69 [95% confidence interval {CI} = 3.45-17.10]) while the Brief
      Alzheimer's Screen most accurately ruled out dementia (LR- = 0.10 [95% CI = 0.02
      0.28]). Using estimates of diagnostic accuracy for AMT-4 from this meta-analysis
      as one trigger for more comprehensive geriatric vulnerability assessments, ED
      dementia screening benefits patients when the prescreening probability of
      dementia is between 14 and 36%. CONCLUSIONS: ED-based diagnostic research for
      dementia screening is limited to a few studies using an inadequate criterion
      standard with variable masking of interpreter's access to the index test and the
      criterion standard. Standardizing the geriatric ED cognitive assessment methods,
      measures, and nomenclature is necessary to reduce uncertainties about diagnostic
      accuracy, reliability, and relevance in this acute care setting. The AMT-4 is
      currently the most accurate ED screening instrument to increase the probability
      of dementia and the Brief Alzheimer's Screen is the most accurate to decrease the
      probability of dementia. Dementia screening as one marker of vulnerability to
      initiate comprehensive geriatric assessment is warranted based on test-treatment
      threshold calculations.

PMID- 30222233
TI  - Racism Is Not a Factor in Door-to-electrocardiogram Times of Patients With
      Symptoms of Acute Coronary Syndrome: A Prospective, Observational Study.
AB  - BACKGROUND: Investigators have identified important racial identity/ethnicity
      based differences in some aspects of acute coronary syndrome (ACS) care and
      outcomes (time to presentation, symptoms, receipt of coronary
      angiography/revascularization, repeat revascularization, mortality). Patient
      based differences such as pathophysiology and treatment-seeking behavior account
      only partly for these outcome differences. We sought to investigate whether there
      are racial identity/ethnicity-based variations in the initial emergency
      department (ED) triage and care of patients with suspected ACS in Canadian
      hospitals. METHODS: We prospectively enrolled ED patients with suspected ACS from
      one university-affiliated and two community hospitals. Trained research
      assistants administered a standardized interview to gather data on symptoms,
      treatment-seeking patterns, and self-reported racial/ethnic identity: "white,"
      South Asian" (SA), "Asian," or "Other." Clinical parameters were obtained through
      chart review. The primary outcome was door-to-electrocardiogram (D2ECG) time. ECG
      times were log-transformed and two linear regression models, controlling for
      important demographic, system, and clinical factors, were fit. RESULTS: Of 448
      participants, 214 (48%) reported white identity, 115 (26%) SA, 83 (19%) Asian,
      and 36 (8%) "Other." Asian respondents were younger and more likely to report
      initial discomfort as "low" and be accompanied by family; respondents identifying
      as "Other" were more likely to report initial discomfort as "high." There was no
      difference in D2ECG time between white participants and all other groups, but
      there were statistically significant differences by sex: women had longer D2ECG
      times than men. Exploring more specific racial identities revealed similar
      findings: no significant differences between the white, SA, Asian, and other
      groups, while sex (women had 13.4% [95% confidence interval, 0.81%-27.57%] longer
      D2ECG times) remained statistically significantly different in the adjusted
      models. CONCLUSION: Although racial/ethnicity-based differences in aspects of ACS
      care have been previously identified, we found no differences in the current
      study of early ED care in a Canadian urban setting. However, female patients
      experience longer D2ECG times, and this may be a target for process improvements.

PMID- 30222234
TI  - Moving Beyond Diagnostic Accuracy With Systematic Reviews and Meta-analyses.

PMID- 30222235
TI  - Mindfulness-based stress reduction for menopausal symptoms after risk-reducing
      salpingo-oophorectomy (PURSUE study): a randomised controlled trial.
AB  - OBJECTIVE: To assess the short- and long-term effects of mindfulness-based stress
      reduction (MBSR) on the resulting quality of life, sexual functioning, and sexual
      distress after risk-reducing salpingo-oophorectomy (RRSO). DESIGN: Randomised
      controlled trial. SETTING: A specialised family cancer clinic of the university
      medical center Groningen. POPULATION: Sixty-six women carriers of the BRCA1/2
      mutation who developed at least two moderate-to-severe menopausal symptoms after
      RRSO. METHODS: Women were randomised to an 8-week MBSR training programme or to
      care as usual (CAU). MAIN OUTCOME MEASURES: Change in the Menopause-Specific
      Quality of Life Questionnaire (MENQOL), the Female Sexual Function Index, and the
      Female Sexual Distress Scale, administered from baseline at 3, 6, and 12 months.
      Linear mixed modelling was applied to compare the effect of MBSR with CAU over
      time. RESULTS: At 3 and 12 months, there were statistically significant
      improvements in the MENQOL for the MBSR group compared with the CAU group (both P
      = 0.04). At 3 months, the mean MENQOL scores were 3.5 (95% confidence interval,
      95% CI 3.0-3.9) and 3.8 (95% CI 3.3-4.2) for the MBSR and CAU groups,
      respectively; at 12 months, the corresponding values were 3.6 (95% CI 3.1-4.0)
      and 3.9 (95% CI 3.5-4.4). No significant differences were found between the MBSR
      and CAU groups in the other scores. CONCLUSION: Mindfulness-based stress
      reduction was effective at improving quality of life in the short- and long-term
      for patients with menopausal symptoms after RRSO; however, it was not associated
      with an improvement in sexual functioning or distress. TWEETABLE ABSTRACT:
      Mindfulness improves menopause-related quality of life in women after risk
      reducing salpingo-oophorectomy.

PMID- 30222236
TI  - Factors associated with first thrombosis in patients presenting with obstetric
      antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and
      International Networking Clinical Database and Repository: a retrospective study.
AB  - OBJECTIVE: To evaluate the subsequent rate of thrombosis among women with
      obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of
      antiphospholipid antibody (aPL)-positive patients, and the clinical utility of
      the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to
      assess the likelihood of developing new thrombosis, in this group of patients.
      DESIGN: Retrospective study. SETTING: The Antiphospholipid Syndrome Alliance for
      Clinical Trials and International Networking Clinical Database and Repository.
      POPULATION: Women with Ob-APS. METHODS: Comparison of clinical and laboratory
      characteristics and measurement of aGAPSS in women with Ob-APS, with or without
      thrombosis, after initial pregnancy morbidity (PM). MAIN OUTCOME MEASURES: Risk
      factors for thrombosis and aGAPSS. RESULTS: Of 550 patients, 126 had Ob-APS;
      74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed
      thrombosis after initial PM, in a mean time of 7.6 +/- 8.2 years (4.9/100 patient
      years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk
      factors, superficial vein thrombosis, heart valve disease, and multiple aPL
      positivity increased the risk of first thrombosis after PM. Women with thrombosis
      after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5
      (4-16) versus 9 (4-13); P = 0.0089]. CONCLUSION: Based on a retrospective
      analysis of our multicentre aPL database, 63% of women with Ob-APS developed
      thrombosis after initial obstetric morbidity; additional thrombosis risk factors,
      selected clinical manifestations, and high-risk aPL profile increased the risk.
      Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the
      registry. We believe that aGAPSS is a valid tool to improve risk stratification
      in aPL-positive women. TWEETABLE ABSTRACT: More than 60% of women with obstetric
      antiphospholipid syndrome had thrombosis after initial pregnancy morbidity.

PMID- 30222238
TI  - Disease progression after ablation for atrial flutter compared with atrial
      fibrillation: A nationwide cohort study.
AB  - AIMS: The aim of this study was to study the risk of death and development of
      arrhythmia and/or subsequently heart failure after an atrial flutter ablation
      procedure compared with an atrial fibrillation (AF) ablation procedure. METHODS:
      This observational study is based on data from Danish nationwide health
      databases. Patients with a first-time ablation procedure for either atrial
      flutter or AF in the period 2000-2016 were included. Rates of renewed arrhythmia,
      heart failure or death were compared and reported as adjusted hazard ratios (HR).
      RESULTS: The study population consisted of 2,004 and 3,803 patients with an
      incident atrial flutter or AF ablation procedure, respectively. All-cause
      mortality among atrial flutter patients was significantly higher compared with
      the AF group (HR 1.80, 95% confidence interval [CI] 1.39-2.35). The incidence of
      renewed arrhythmia without heart failure was lower in atrial flutter (HR 0.76,
      95% CI 0.69-0.84). Renewed atrial flutter ablation and pacemaker implantations
      were significantly more frequent (HR 2.42, 95% CI 2.02-2.91 and HR 1.42, 95% CI
      1.13-1.79, respectively) in atrial flutter compared with AF. The risk of heart
      failure was higher for atrial flutter, both after the initial ablation (HR 1.48,
      95% CI 1.08-2.03), and after a further arrhythmia management event (HR 1.98, 95%
      CI 1.33-2.94). CONCLUSION: There was a higher mortality risk after atrial flutter
      ablation procedures compared with patients undergoing AF ablation. Rates of heart
      failure and further renewed (non-AF) arrhythmia management were higher in atrial
      flutter.

PMID- 30222237
TI  - Incidence and outcomes of long QTc in acute medical admissions.
AB  - AIMS: Prolonged QT interval on electrocardiogram (ECG) increases the risk of
      ventricular arrhythmia. Patients admitted to acute medical units (AMU) may be at
      risk of QT prolongation from multiple, recognised risk factors. Few data exist
      regarding incidence or outcomes of QT prolongation in acute general medical
      admissions. The aims were to determine the incidence of Bazett's-corrected QT
      (QTc) prolongation upon admission to AMU; the relationship between QTc and
      inpatient mortality, length of stay and readmission; proportion with prolonged
      QTc subsequently administered QT interval-prolonging drugs. METHODS:
      Retrospective, observational study of 1000 consecutive patients admitted to an
      AMU in a large urban hospital. EXCLUSION CRITERIA: age <18 years, ventricular
      pacing, poor quality/absent ECG. QTc determined manually from ECG obtained within
      4-hours of admission. QTc prolongation considered >=470 milliseconds (males) and
      >=480 milliseconds (females). In both genders, >500 milliseconds was considered
      severe. Study end-points, (a) incidence of QTc prolongation at admission; (b)
      inpatient mortality, length of stay and readmission rates; (c) proportion with
      QTc prolongation subsequently administered QT interval-prolonging drugs. RESULTS:
      Of 1000 patients, 288 patients were excluded, therefore final sample was n = 712.
      Patient age (mean +/- SD) was 63.1 +/- 19.4 years; females 49%. QTc prolongation
      was present in n = 50 (7%) at admission; 1.7% had QTc interval >500 ms. Of the 50
      patients admitted with prolonged QTc, 6 (12%) were subsequently administered QT
      interval-prolonging drugs. QTc prolongation was not associated with worse
      inpatient mortality or readmission rate. Length of stay was greater in those with
      prolonged QTc, 7.2 (IQR 2.4-13.2) days vs 3.3 (IQR 1.3-10.0; P = 0.004), however,
      in a regression model, presence of QTc did not independently affect length of
      stay. CONCLUSIONS: QTc interval prolongation is frequent among patients admitted
      to AMU. QT interval-prolonging drugs are commonly prescribed to patients
      presenting with prolonged QTc but whether this affects clinical outcomes is
      uncertain.

PMID- 30222239
TI  - The Crystal Structure of a Class of Cyclases that Catalyze the Cope
      Rearrangement.
AB  - Found recently in stignomatales, the Stig cyclases catalyze the Cope
      rearrangement and intramolecular cyclization to produce complex indole alkaloids.
      Five crystal structures were solved of subfamily 1 and 2 Stig cyclases, which
      adopt a beta-sandwich fold like the non-catalytic carbohydrate-binding motif.
      Several complex structures were also determined of indole-based compounds, which
      are bound to the hydrophobic terminal cavity, where a conserved Asp residue makes
      an H-bond to the indole N and triggers the acid-catalyzed Cope rearrangement.
      Through analyzing the enzyme-ligand interactions and mutagenesis experiments,
      several aromatic residues were found important in catalysis. Apart from a common
      substrate binding mode and catalytic mechanism, potential subfamily variations
      that may attribute to the different product specificity are implicated. These
      results shall expand our scope of enzymology, in particular for further
      investigation of the biosynthetic Cope rearrangement.

PMID- 30222240
TI  - Physical examination to screen for peripheral artery disease in a defined Primary
      Care population: A diagnostic accuracy study.
AB  - INTRODUCTION: Peripheral arterial disease (PAD) is an underdiagnosed prevalent
      disease which implies high cardiovascular risk. Professionals usually depend on
      physical examination to screen for PAD. OBJECTIVE: To assess the diagnostic
      accuracy of physical examination to screen for PAD in a rural Primary Care
      population and to evaluate the nurse-physician level of agreement in pedal pulse
      palpation. METHODS: Diagnostic accuracy study in which two experienced
      professionals (physician-nurse) prospectively performed pedal pulse palpation
      (grading as absent, reduced, normal, or bounding), femoral bruit auscultation and
      calf circumference (index tests) comparing with Doppler ABI (reference test,
      positive cut-off: 0.9 >= ABI >= 1.4) in 158 consecutive subjects. INCLUSION
      CRITERIA: presence of diabetes, dyslipidaemia, hypertension, smoking habit
      (current or former), or age >= 65. RESULTS: Of 315 legs included, PAD was
      confirmed in 38 (12.1%) legs. Absent dorsalis pedis (DP) and posterior tibial
      (PT) pulses were found in 37 (11.7%) and 67 (21.3%) legs, respectively. Regarding
      nurse evaluation, when a positive test was set if DP or PT were absent (more
      sensitive cut-off), sensitivity was = 86.8 (95% CI: 74.8-98.9), specificity =
      82.7 (95% CI: 78.0-87.3), likelihood ratio+ = 5.01 (95% CI: 3.77-6.67),
      likelihood ratio- = 0.16 (95% CI: 0.07-0.36), and diagnostic odds ratio (dOR) =
      31.5 (95% CI: 11.7-84.8). Age, diabetes, and calcification (ABI >= 1.4)
      influenced the rate of a false negative finding in pedal palpation. Physician
      nurse weighted kappa coefficient was = 0.649 (95% CI: 0.599-0.699). The presence
      of a femoral bruit auscultation had a dOR = 3.8 (95% CI: 1.1-13.1), and a calf
      circumference <34.55 cm had a dOR = 3.2 (95% CI: 1.6-6.4). CONCLUSIONS AND
      RELEVANCE: In a mainly asymptomatic Primary Care population, pedal pulse
      palpation was by far the best diagnostic test, with good diagnostic accuracy and
      inter-rater agreement. In view of a high sensitivity and capacity to rule out the
      disease, pedal pulse palpation could be performed as a screening test for PAD and
      individuals at high cardiovascular risk.

PMID- 30222241
TI  - Treatment for erectile dysfunction among older men in Northern Ireland.
AB  - BACKGROUND: Erectile dysfunction is common among older men; however, diagnosis
      and treatment compared to reported prevalence is low. We aim to identify the
      degree to which older men are offered treatment for the condition and determine
      the level of unmet need within Northern Ireland (NI). METHODOLOGY: Analysis of
      data collected using a cross-sectional survey was conducted for men aged >=60
      years with data weighted to the NI population by age and deprivation. Respondents
      answered questions on sociodemographic factors, health-related characteristics,
      ability to function sexually, level of sexual interest and activity, and any
      treatment offered to improve erections in the last 3 years. Results are presented
      as proportions reporting treatment receipt, with differences by respondent
      characteristics assessed using chi-square tests and multivariable logistic
      regression. RESULTS: Among 2597 respondents, 46.5% reported erectile dysfunction.
      One quarter (25.8%) recalled being offered either medication, devices, or
      specialised services to improve erections. The offer of treatment was associated
      with younger age, being separated or divorced, higher number of long-term
      conditions, and greater interest in sex. Of men reporting erectile dysfunction
      and offered medication, 28.8% found them helpful and currently use them.
      CONCLUSIONS: As a result of not being offered treatment or not finding treatment
      useful, 93% of men reporting erectile dysfunction have no help with the
      condition. This is a likely consequence of treatment availability through the NHS
      in NI, but also suggests that healthcare professionals need to engage more
      proactively with older men, discussing sexual health routinely and following up
      those treated for the condition.

PMID- 30222242
TI  - Successful heart-kidney transplantation from a Hepatitis C viremic donor to
      negative recipient: One year of follow-up.
AB  - Every year the number of patients waiting for a heart transplant increases faster
      than the number of available donor organs. Some potential donor organs are from
      donors with active communicable diseases, including hepatitis C virus (HCV),
      potentially making donation prohibitive. The advent of direct-acting antiviral
      agents for HCV has drastically changed the treatment of HCV. Recently, these
      agents have been used to treat HCV in organ donor recipients who acquired the
      disease from the donor organ. We report a case of heart-kidney transplantation
      from an HCV viremic donor to HCV negative recipient with successful treatment and
      sustained virologic response.

PMID- 30222243
TI  - Adenine-Driven Structural Switch from a Two- to Three-Quartet DNA G-Quadruplex.
AB  - A G-rich sequence found in the regulatory region of the RANKL gene, which is
      associated with homeostasis of bone metabolism, folds into a two-quartet basket
      type G-quadruplex stabilized by A?G?A and G?G?G base-triads. Perusal of local
      structural features together with G/A-to-T modifications uncovered the critical
      role of A5 for the formation of a distinct antiparallel two-quartet topology and
      not the three-quartet topology that would be expected based on the sequence with
      four GGG-tracts alone. The structural changes induced by the A5-to-T5
      modification include a switch in orientation and relative positions of G-strands
      that together with anti to syn reorientation of G12 provide insights into the
      complexity of the interactions that influence the folding of G-rich DNA.
      Understanding the impact of loop residues on the stability and formation of G
      quadruplexes advances our knowledge and ability to predict structures adopted by
      G-rich sequences, which are involved in regulatory mechanisms in the cell, and
      may also facilitate drug design.

PMID- 30222244
TI  - The use of mouthguards and prevalence of dento-alveolar trauma among athletes: A
      systematic review and meta-analysis.
AB  - BACKGROUND/AIMS: The evidence that mouthguards prevent dental trauma is
      inconsistent. The aim of this study was to determine, through a systematic review
      and meta-analysis (MA), the impact of mouthguards (MG) on the prevalence of dento
      alveolar trauma (DT) among athletes of contact sports. MATERIAL AND METHODS:
      Searches were performed at Medline, Scopus, Web of Science, Lilacs, Cochrane
      Library, and SIGLE without restriction of language or publication date. After the
      application of eligibility criteria, studies were evaluated regarding their
      methodology quality and risk of bias. Two meta-analyses (MA) were performed
      considering: studies free of problems or with minor problems (MA1) and only free
      of problems studies (MA2). DT prevalence (events) and total number of athletes
      from each group (use of MG and non-use of MG) were used for odds ratio
      calculation (alpha = 5%). The evidence was quality tested using the GRADE
      approach. RESULTS: A total of 256 articles were identified. After applying the
      eligibility criteria, 14 studies were selected for qualitative synthesis, and 11
      were used in quantitative synthesis. Meta-analyses showed that 73% (MA1) and 83%
      (MA2) of mouthguard users have a lower prevalence of DT. In MA1 (eight studies),
      DT prevalence among MG users was 7.75% (n = 183), while non-users had 48.31% (n =
      974) (OR = 0.18, 95% CI = 0.07-0.45, P < 0.001). In MA2 (three studies), DT
      prevalence among MG users was 7.5% (n = 160), while DT prevalence among non-users
      was 59.48% (n = 750) (OR = 0.10, 95% CI = 0.05-0.08, P < 0.001), with moderate
      evidence quality level. CONCLUSION: Mouthguards contribute to a lower prevalence
      of dento-alveolar trauma among athletes of contact sports.

PMID- 30222245
TI  - Synchrotron Big Data Science.
AB  - The rapid development of synchrotrons has massively increased the speed at which
      experiments can be performed, while new techniques have increased the amount of
      raw data collected during each experiment. While this has created enormous new
      opportunities, it has also created tremendous challenges for national facilities
      and users. With the huge increase in data volume, the manual analysis of data is
      no longer possible. As a result, only a fraction of the data collected during the
      time- and money-expensive synchrotron beam-time is analyzed and used to deliver
      new science. Additionally, the lack of an appropriate data analysis environment
      limits the realization of experiments that generate a large amount of data in a
      very short period of time. The current lack of automated data analysis pipelines
      prevents the fine-tuning of beam-time experiments, further reducing their
      potential usage. These effects, collectively known as the "data deluge," affect
      synchrotrons in several different ways including fast data collection, available
      local storage, data management systems, and curation of the data. This review
      highlights the Big Data strategies adopted nowadays at synchrotrons, documenting
      this novel and promising hybridization between science and technology, which
      promise a dramatic increase in the number of scientific discoveries.

PMID- 30222246
TI  - The structure of INI1/hSNF5 RPT1 and its interactions with the c-MYC:MAX
      heterodimer provide insights into the interplay between MYC and the SWI/SNF
      chromatin remodeling complex.
AB  - c-MYC and the SWI/SNF chromatin remodeling complex act as master regulators of
      transcription, and play a key role in human cancer. Although they are known to
      interact, the molecular details of their interaction are lacking. We have
      determined the structure of the RPT1 region of the INI1/hSNF5/BAF47/SMARCB1
      subunit of the SWI/SNF complex that acts as a c-MYC-binding domain, and have
      localized the interaction regions on both INI1 and on the c-MYC:MAX heterodimer.
      c-MYC interacts with a highly conserved groove on INI1, while INI1 binds to the c
      MYC helix-loop-helix region. The binding site overlaps with the c-MYC DNA-binding
      region, and we show that binding of INI1 and E-box DNA to c-MYC:MAX are mutually
      exclusive.

PMID- 30222247
TI  - Autophagy and mitochondrial metabolism: insights into their role and therapeutic
      potential in chronic myeloid leukaemia.
AB  - Despite the development of selective BCR-ABL-targeting tyrosine kinase inhibitors
      (TKIs) transforming the management of chronic myeloid leukaemia (CML), therapy
      resistant leukaemic stem cells (LSCs) persist after TKI treatment and present an
      obstacle to a CML cure. Recently, we and others have made significant
      contributions to the field by unravelling survival dependencies in LSCs to work
      towards the goal of eradicating LSCs in CML patients. In this review, we describe
      these findings focusing on autophagy and mitochondrial metabolism, which have
      recently been uncovered as two essential processes for LSCs quiescence and
      survival respectively. In addition, we discuss the therapeutic potential of
      autophagy and mitochondrial metabolism inhibition as a strategy to eliminate CML
      cells in patients where the resistance to TKI is driven by BCR-ABL-independent
      mechanism(s).

PMID- 30222248
TI  - Injectable Hydrogel of Vitamin B9 for the Controlled Release of Both Hydrophilic
      and Hydrophobic Anticancer Drugs.
AB  - Folic acid (FA), vitamin B9 , is a good receptor of drugs triggering cellular
      uptake via endocytosis. FA is sparingly soluble in water. Herein, a new approach
      for the formation of FA hydrogel by the hydrolysis of glucono-delta-lactone in
      PBS buffer under physiological conditions has been reported. The gel has a
      fibrillar network morphology attributable to intermolecular H-bonding and pi
      stacking interactions. The thixotropic property of the gel is used for the
      encapsulation of both hydrophilic [doxorubicin (DOX)] and hydrophobic
      [camptothecin (CPT)] drugs. The loading of DOX and CPT into the gel is attributed
      to the H-bonding interaction between FA and drugs. The release of DOX is
      sustainable at pH 4 and 7, and the Peppas model indicates that at pH 7 the
      diffusion of the drug is Fickian but it is non-Fickian at pH 4. The release of
      CPT is monitored by fluorescence spectroscopy, which also corroborates the
      combined release of both drugs. The metylthiazolyldiphenyltetrazolium bromide
      assay of FA hydrogel demonstrates nontoxic behavior and that the cytotoxicity of
      the DOX-loaded FA hydrogel is higher than that of pure DOX, with a minimal effect
      on normal cells.

PMID- 30222249
TI  - RNA-seq: Basic Bioinformatics Analysis.
AB  - Quantitative analysis of gene expression is crucial for understanding the
      molecular mechanisms underlying genome regulation. RNA-seq is a powerful platform
      for comprehensive investigation of the transcriptome. In this unit, we present a
      general bioinformatics workflow for the quantitative analysis of RNA-seq data and
      describe a few current publicly available computational tools applicable at
      various steps of this workflow. These tools comprise a pipeline for quality
      assessment and quantitation of RNA-seq data that starts from raw sequencing files
      and is focused on the identification and analysis of genes that are
      differentially expressed between biological conditions. (c) 2018 by John Wiley &
      Sons, Inc.

PMID- 30222250
TI  - Bone Marrow Chimeras to Study Neuroinflammation.
AB  - Bone marrow transplantation is the standard of care for a host of diseases such
      as leukemia and multiple myeloma, as well as genetically inherited metabolic
      diseases affecting the central nervous system. In mouse models, bone marrow
      transplantation has proven a valuable tool for understanding the hematopoietic
      system and the homing of hematopoietic cells to their target organs. Many
      techniques have been developed to create chimeric mice, animals with a
      hematopoietic system derived from a genetic background that differs from the rest
      of the body. Current genetic tools allow for virtually limitless possibilities in
      the choice of donor mice. This protocol describes methods of bone marrow
      transplantation in mouse models for studies of the brain under basal and
      pathological conditions. Specific points to be addressed include the preparation
      of recipient mice by irradiation or chemotherapy; the choice, isolation, and
      injection of donor cells; and analytical methods such as fluorescence-activated
      cell sorting and immunostaining. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30222251
TI  - Tyrosine phosphorylation of a receptor-like cytoplasmic kinase, BSR1, plays a
      crucial role in resistance to multiple pathogens in rice.
AB  - Plants have evolved many receptor-like cytoplasmic kinases (RLCKs) to modulate
      their growth, development, and innate immunity. Broad-Spectrum Resistance 1
      (BSR1) encodes a rice RLCK, whose overexpression confers resistance to multiple
      diseases, including fungal rice blast and bacterial leaf blight. However, the
      mechanisms underlying resistance remain largely unknown. In the present study, we
      report that BSR1 is a functional protein kinase that autophosphorylates and
      transphosphorylates an artificial substrate in vitro. Although BSR1 is classified
      as a serine/threonine kinase, it was shown to autophosphorylate on tyrosine as
      well as on serine/threonine residues when expressed in bacteria, demonstrating
      that it is a dual-specificity kinase. Protein kinase activity was found to be
      indispensable for resistance to rice blast and leaf blight in BSR1-overexpressing
      plants. Importantly, tyrosine phosphorylation of BSR1 was critical for proper
      localization of BSR1 in rice cells and played a crucial role in BSR1-mediated
      resistance to multiple diseases, as evidenced by compromised disease resistance
      in transgenic plants overexpressing a mutant BSR1 in which Tyr-63 was substituted
      with Ala. Overall, our data indicate that BSR1 is a non-receptor dual-specificity
      kinase and that both tyrosine and serine/threonine kinase activities are critical
      for the normal functioning of BSR1 in the resistance to multiple pathogens. Our
      results support the notion that tyrosine phosphorylation plays a major regulatory
      role in the transduction of defense signals from cell-surface receptor complexes
      to downstream signaling components in plants.

PMID- 30222252
TI  - Investigating Subcellular Compartment Targeting Effect of Porous Coordination
      Cages for Enhancing Cancer Nanotherapy.
AB  - Understanding the key factors for successful subcellular compartment targeting
      for cargo delivery systems is of great interest in a variety of fields such as
      bionanotechnology, cell biology, and nanotherapies. However, the fundamental
      basis for intracellular transportation with these systems has thus far rarely
      been discussed. As a cargo vector, porous coordination cages (PCCs) have great
      potential for use in cancer nanotherapy and to elucidate fundamental insight
      regarding subcellular compartment targeting. Herein, it is shown that the
      transportation of PCC cargo vectors though various subcellular barriers of the
      mammalian cell can be manipulated by tuning the vector's electronic property and
      surface affinity. It is found that the PCCs become selectively aggregated at the
      cell membrane, the cytoplasm, or the nucleus, respectively. When a DNA
      topoisomerase inhibitor is delivered into the nucleus by a neutral and lipophilic
      PCC, the anticancer efficacy is dramatically improved. The findings shed light to
      tune the interactions at the "bio-nano" interface. This study provides a key
      strategy for future work in targeting specific cell organelles for cell imaging,
      cargo delivery, and therapy. This research also offers key insight into the
      engineering of nanoscopic materials for furnishing cell organelle-specificity.

PMID- 30222253
TI  - Acute kidney injury secondary to traumatic rhabdomyolysis in a dog.
AB  - OBJECTIVE: To describe the clinical course and successful management of a dog
      with crush syndrome, rhabdomyolysis, myoglobinuria, and associated acute kidney
      injury (AKI). CASE SUMMARY: An 8-year-old female, neutered, mixed-breed dog was
      referred to the Veterinary Teaching Hospital due to crush injury and suspected
      AKI. Blood tests and urinalysis showed markedly increased serum creatine kinase
      activity, myoglobinuria, and AKI. The dog was managed successfully with
      intermittent hemodialysis, and completely recovered. NEW OR UNIQUE INFORMATION
      PROVIDED: This is the first report of a dog with crush syndrome with secondary
      myoglobinuria and AKI.

PMID- 30222254
TI  - Out-of-Band Radiation and Spatio-Temporal Characterization of Gd Target Laser
      Plasma Sources.
AB  - In this paper, an Nd?YAG laser with 10ns pulse width and output wavelength of 1
      064 nm was employed to ablate Gd metal target and Gd-doped glass target for
      plasma generation. The out-of-band (OOB) radiation of extreme ultraviolet sources
      with the two target configurations was comparatively studied. It has been found
      that the continuous radiation emitted by the plasma is the main component of the
      out-of-band radiation. The spectral distribution of the continuum emission
      matches that of blackbody radiation with a temperature of about 5 eV. And it is
      also found that the intensity of OOB radiation can be considerably decreased by
      using Gd-doped glass target. Optical Emission Spectroscopy (OES) has been used to
      analyze the temporal and spatial behaviors of electron temperature (Te) and
      density (Ne) of the Gd-doped glass target plasma, and experimental results show
      that temporal evolution of electron temperature and density of the plasma are
      found to be decayed exponentially with the increasing of delay time. At 125 ns
      after laser irradiation, electron temperature and density were 4 eV and 1.2*1018
      cm-3 respectively, and then decreased to 1.5 eV and 8*1017 cm-3 with delaying
      time of 250 ns. On the other hand, spatial evolution of electron temperature and
      density show that both of them first increase and then decrease in the region of
      1~10 mm from the target surface. The electron temperature and electron density
      achieves the maximum of 2.6 eV and 8.5*1017 cm-3, respectively, when the probe
      location away from the target surface 6 mm.

PMID- 30222255
TI  - RGBW Signal Mapping Algorithm Assessment Based on Colorimetry.
AB  - With the continuous pursuit of high brightness and low power consumption display
      technology, RGBW display technology has been attracting increasing attention in
      the world. Various kinds of displays based on this technology have been produced
      in the market. The key of this technology is signal mapping algorithm which
      converts RGB signal into RGBW signal without color distortion and compatible with
      different sub-pixel layouts. This paper, on the basis of five kinds of signal
      mapping algorithms, analyzes the mode of action of newly added white sub-pixel
      affects display color, and the display performance affected by four kinds of sub
      pixel layouts; it proposes the corresponding condition of excellent signal
      mapping algorithm based on colorimetry and deduces the universal equation of
      excellent signal mapping algorithm and brightness factor which could measure the
      ability of enhancing brightness. The simulation experiment shows that the signal
      mapping algorithm which satisfies universal equation could be able to maintain
      the hue and saturation better. The signal mapping algorithm's ability to enhance
      brightness is effectively characterized by brightness factor. In conclusion, the
      proposed universal equation can be used to evaluate existing signal mapping
      algorithms, and it provides theoretical references for the research of new signal
      mapping algorithm which could be compatible with different hardware parameters
      and sub-pixel layouts, promote the popularization of RGBW display technology.

PMID- 30222256
TI  - Experimental Study on the Characteristics of Chemiluminescence in Coal Water
      Slurry Diffusion Flames Based on Hot Oxygen Burner Technology.
AB  - Most published works focused on the characteristics of chemiluminescence in
      homogeneous flames, but the research about radiation spectrum in heterogeneous
      flames was still limited. In this paper, improved hot oxygen burner (HOB)
      technology is applied to ignite coal water slurry (CWS) directly in the open
      space, for stable combustion. Radiation spectrum and two-dimensional OH*
      chemiluminescence in methane and CWS diffusion flames are measured by a fiber
      optic spectrometer and a high-spatial-resolution UV imaging system. The results
      show that OH* (309.12 nm), CH* (431.42 nm) and C2* (463.52~563.43 nm) radicals
      exist in both methane and CWS diffusion flame, but Na* (589.45 nm), Li* (670.88
      nm), K* (766.91, 770.06 nm), H* (816.04, 819.99 nm) radiation spectrum line and
      continuous black-body radiation have been detected only in the CWS flame. These
      differences can be used to characterize the combustion or gasification of CWS and
      distinguish whether CWS is ignited or not. In addition, the injection of CWS into
      methane flame leads to a significant reduction in OH* and an increase in C2* and
      CH* radiation intensity. This is because a lot of heat is absorbed in the
      processes of CWS combustion reactions. Then the generation of CH is inhibited,
      and the production of OH* is reduced. The increase of C2* and CH* is due to
      simple substance carbon produce more after injecting CWS. Besides, axial OH*
      radiation intensity increases at first then decreases, and the position of peak
      intensity is closer to outlet of hot oxygen burner compared with methane flames.
      Radial OH* radiation distribution is bimodal in methane flame because reactions
      take place in the thin layer where methane and oxygen meet. However, in CWS
      flame, radial OH* radiation distribution is always unimodal since CWS diffuses
      fiercely and mixes with oxygen sufficiently. As the ratio of oxygen atom to
      carbon atom ([O/C]e) increases, the reaction region of OH* radicals becomes
      larger in methane and CWS flame. This indicates that increasing oxygen can
      promote reactions and benefit OH* radicals' generation. Moreover, with the
      increase of CWS flow, reaction center is closer to burner outlet, OH*
      distribution range and peak intensity decrease obviously, CH*, C2*, Na*, Li*, K*,
      H* and black-body radiation intensities markedly rise. And these characteristics
      can reflect the changes of operation loads.

PMID- 30222257
TI  - The Inside Charge Behavior of Organic Light-Emitting Diodes Investigated with
      Transient Electroluminescent Measurements.
AB  - Transient electroluminescent measurement system is used to study the inside
      charge behavior of prepared organic light-emitting diodes (OLEDs) in this
      article. Two rectangular pulses with a fixed time interval are supplied on the
      device. We can analyze the inside charge storage and the emitting process by
      measuring the transient EL and transient current of the device. OLEDs based on
      the m-MTDATA?3TPYMB (1?1) system was prepared. We found that the stable EL
      intensity increase when the second pulse is supplied. And the increment reduced
      with the increased current. We also find the electroluminescent under the second
      pulse decayed faster than that of the first pulse. This is because of the
      quenching due to the polaron-exciton effect (TPQ) is more serious in the emitting
      layer under the second pulse.

PMID- 30222258
TI  - Research on the Development of Light Blending Model for Smart LED Lighting.
AB  - The color of the LED smart light is tunable by its inner equipped micro
      processing systems. Therefore, it could provide significant improvement for the
      smart lighting conditions, such as museum lighting and home lighting. At present,
      the limitation of the current lighting blending technology remarkably affects the
      application of smart lighting technology and people could not make full use of
      the adjustability of the smart luminaries. In this research, a novel light
      blending model was proposed based on BP neural network and active set algorithm.
      The models could effectively simulate the nonlinear relationship between the
      device control values of the smart light and the output radiance spectrum of the
      light. Particularly, a BP neural network-based forward model for LED light
      blending was firstly proposed, which could accurately calculate the spectral
      radiance power distribution from the device control values. Afterwards, based on
      forward model, an active set algorithm-based backward model was developed, which
      could precisely predict the device control values from the desired spectral
      radiance power distribution. The experimental result indicates that the proposed
      method could accurately achieve the light blending controlling of smart LED
      light, with a CIEUCS Duv value of 0.002 7, which is significantly smaller than
      the just noticeable difference value of human vision. The authors believe that
      the proposed method will provided effective support for the development of smart
      LED lighting in near future.

PMID- 30222259
TI  - The NIR Spectral Characteristics and Meaning of Fault Gouge from Kaxiutata Iron
      Deposit, Inner Mongolia.
AB  - Kaxiutata iron deposit is a skarn type magnetite deposit located in Inner
      Mongolia, China. There are many faults developed after metallogenic period. In
      this study, NIR analysis method is adopted to identify the mineral composition of
      subsurface and surface fault gouge from mining area. Through the characteristic
      peaks, it is was identified that there are mainly mafic mineral in the subsurface
      fault gouge and salic minerals in the surface fault gouge, the sand sample for
      comparison contain both two types of minerals. The result of analysis of all
      three sets of sample is in accordance with the geological background of the
      sampling spot. According to this research, due to the main composition of the
      fault gouge in the mineralization area are clay formed due to the faulting
      movement and altered minerals formed in early metallogenic period. NIR analysis
      technology is suitable for this type of sample, to use this technology, we can
      identify the clay mineral in the fault gouge, and further speculate the
      composition of protolith of clay,we can also indentify the altered minerals
      formed in metallogenic period, and provide useful information for study of
      hydrothermal deposit.

PMID- 30222260
TI  - A New Feature Extraction Method of Near-Infrared Spectra Based on the Addition of
      Historical Data.
AB  - In traditional qualitative analysis of near-infrared (NIR) spectra, the stability
      of recognition models is decreased when new varieties of samples are added into
      the model. In order to improve the robustness of the model, a new feature
      extraction method based on the addition of historical data was put forward. The
      NIR training samples will be collected first, after that the historical data of
      the same species is added to constitute a larger and richer dataset. Then, the
      pretreated data of these training samples is projected to the feature space,
      which is constructed by feature extraction using partial least squares (PLS)
      based on the above dataset. Subsequently, orthogonal linear discriminant analysis
      (OLDA) is employed to extract features of the projected data. 18 varieties of
      corn seeds were taken as study subject, the comparative experiments with and
      without historical data are implemented respectively, and then the biomimetic
      pattern recognition (BPR) method is applied to verify the efficiency of the
      method proposed. The results suggest that the method adopted can improve the
      robustness of recognition model more effectively compared with the method without
      historical data. It maintains the high correct recognition ratios when new
      varieties are added into the model. Besides that, the recognition effect on test
      sets of the different days remains the same basically in the condition of same
      PLS dimensions. Therefore, the dimension of feature extraction can be set to some
      fixed values in recognition software. In this way, it can keep out of the trouble
      of manually modifying the optimal PLS parameter in recognition software if new
      varieties need to be added into the model. The experiment results of the thesis
      manifested the effectiveness of the proposed method.

PMID- 30222261
TI  - Logistics Process Safety System of Table Grapes Based on NIR.
AB  - In view of the actual logistics process of table grapes and the situation that
      fresh keeping agents based on sulfur dioxide are commonly used in table grape
      logistics, we studied the shelf life prediction method of table grapes under 4
      temperatures and constant concentrations of sulfur dioxide based on near infrared
      spectrum (NIR) and the evolution of texture in this work. Logistics process
      safety system based on shelf life prediction was designed to reduce the loss of
      table grapes in the logistics. The change of texture is an important cause of
      postharvest table grapes to end their shelf life in postharvest logistics. In
      this work, we used SO2 concentration sensors to control solenoid valves, and
      obtained the set SO2 concentrations by automatic compensation mechanism. The
      evolutions of table grape texture under different concentrations of sulfur
      dioxide were studied as well as the influence of temperature. The NIR
      pretreatment effects of multiplicative scatter correction and the first S-G
      derivation were compared. The table grape texture nondestructive testing model
      built base on NIR and partial least squares regression achieved a determination
      coefficient of 0.93 and the root mean squared error (RMSE) was 1.70. In full
      cross-validation, the prediction accuracy reached to 0.81 and got a RMSE of 2.91.
      Research indicated that the NIR detection combined with the quality change
      modeling and information technology could be used to improve the logistics
      process safety management efficiency of postharvest fruits and vegetables.

PMID- 30222262
TI  - Infrared Spectrum Studies of Coatings under Irradiation of Sunlight and
      Ultraviolet.
AB  - Degradable resin- coated controlled release fertilizer is one of the hottest
      current research focuses in the field of fertilizer. In terms of practical
      application, the photodegradability characteristics of three kinds of coatings
      including polyethylene/hydrophilic nano-TiO2 composite, polyethylene/hydrophilic
      nano-TiO2 composite and pure polyethylene were analyzed under irradiation of
      sunlight and ultraviolet by ATR-FTIR, which was aimed to know their degradation
      behaviors under two conditions. The result showed that under irradiation of
      sunlight and ultraviolet, the type of functional group was not changed with the
      addition of the photo-catalyst, but the photo-catalyst just had an effect on
      intensity of functional groups. The trend was polyethylene/hydrophobic nano-TiO2
      composite>polyethylene/hydrophilic nano-TiO2 composite>pure polyethylene.
      Furthermore, sunlight and ultraviolet had different effects on molecular
      structures of coatings. Under irradiation of sunlight, crosslinking reaction took
      place and ether bond was generated among the carbon chain of polyethylene except
      for the form of hydroperoxides. Then, carbon chain continued being oxidized to
      form carbonyl group. The existence of carbonyl group promoted the further
      degradation of coatings; under irradiation of ultraviolet, high local
      concentrations of reactive oxygen species were produced and the ability to attack
      the carbon chain of polymer was strong. Thus, the long alkyl chain of
      polyethylene was quickly oxidized to form intermediate products containing
      carbonyl groups. However, the irradiation experiment of ultraviolet didn't fully
      reveal the degradation behavior of coatings.

PMID- 30222263
TI  - Investigation on Spectral Characteristic and Threshold Behavior of Network
      Structure of Ge-Sb-S Chalcogenide Glasses.
AB  - Two series of chalcogenide glasses in Ge-Sb-S ternary system were synthesized
      with melt-quenching method. The phycochemical properties and spectral
      characteristic of glasses with different content of Ge and Sb were obtained with
      a series of measurements, and the systematic analysis on the change of optical
      properties was conducted in terms of microstructure of glasses combined with the
      Raman spectra. With constraint theory based on mean coordination number (Z), we
      described the variation trend of network structure directly. It was found that as
      long as the value of Z reaches 2.6, new vibration peaks would be formed in the
      Raman spectra indicating the presence of threshold behavior as well as the change
      of the network structure of the Ge-Sb-S glasses which could be expressed in a
      specific varition in the number of metal bonds and the nonmetal bonds. The
      appearance of new functional groups in the network have changed the total bond
      energy of glasses, and then affected the energy band structure of glasses
      representing the corresponding threshold behavior of the value of optical band
      gap (Eopg).

PMID- 30222264
TI  - Quick Discrimination of Rice Storage Period Based on Manifold Dimensionality
      Reduction Methods and Near Infrared Spectroscopy Techniques.
AB  - This paper proposed a method for rapid identification of rice storage period
      based on manifold dimensionality reduction algorithms and near infrared
      spectroscopy (NIRS) technique. The reflection spectrum curve of old rice and new
      rice were obtained with a field spectroradiometer and the acquired spectral data
      was preprocessed with direct orthogonal signal correction method (DOSC) to filter
      the independent signal from the spectral data which is irrelevant with the
      dependent variable Y array and eliminate the influence and interference of the
      irrelevant information in the following chemometric analysis. The Durbin-Watson
      test and Run test methods were utilized to detect the nonlinearity which exists
      in the spectral data structure. The enhanced partial residual plot analysis
      method (Augmented partial residual plot) was employed to quantitative analysis of
      the degree of nonlinearity of the spectral data. Popular linear manifold
      dimensionality reduction methods including principal component analysis (PCA)
      method and multidimensional scaling analysis (MDS) method and popular nonlinear
      manifold dimensionality reduction methods including Isometries mapping method
      (ISOMAP), locally linear embedding (LLE) method and Laplacian Eigenmap method
      (LE) were used to extract the real variable from the preprocessed spectral data.
      Then, the intrinsic variable was taken as the input of the kernel partial least
      squares method (KPLS) to establish the relationship between the intrinsic
      variables and the storage time of rice samples. The number of experiment samples
      of the new rice and the old rice were 200 respectively and randomly separated
      into the training set with 300 samples and the test set with 100 samples. Through
      comparing the prediction results of the regression models which were established
      with different manifold reduction methods, the experiment results show that the
      prediction effects of the nonlinear-based models are superior to the linear-based
      models. Finally, the KPLS model established with 40 true variables extracted with
      ISOMAP approach achieved the optimal prediction effect. The prediction
      correlation coefficient (R2p), RMSEP (RMSEP) and relative prediction error value
      (RPD) were 0.917, 0.187 and 2.698, respectively. It was concluded that NIRS
      combined with ISOMAP-KPLS method can be successfully used to determine the
      storage period of rice accurately and quickly. The study provides a scientific
      means for rapid non-destructive detecting for rice storage period research in the
      future.

PMID- 30222265
TI  - Mid-Infrared Trace CH4 Detector Based on TDLAS-WMS.
AB  - In order to detect trace methane (CH4) with non-contact method, a trace CH4
      detector is designed and developed with the combination of tunable diode laser
      absorption spectroscopy (TDLAS) and wavelength modulation spectroscopy (WMS)
      detection technology, using the absorption line (1 332.8 cm-1) of CH4 in mid
      infrared band. The instrument uses mid-infrared quantum cascaded laser (QCL) with
      centre wavelength at 7.5 MUm, and uses the method of changing the injecting
      current (0.6~1.6 A) of QCL with fixed working temperature to make the emission
      wavelength of QCL to scan the methane's absorption line (1 332.8 cm-1) via tuning
      parameters 0.2 cm-1.A-1. In terms of optical structure, the instrument using a
      gas absorption sealed herriott cell with 76 m long optical path, cooperating with
      difference detection optical path, reduces the noise which caused by the
      fluctuation of QCL, and guarantees the detection of trace CH4. In the experiment,
      we adopted minimum mean square error criterion to fit the relationship between
      methane concentration and harmonic peak signal. In addition, the minimum
      detection limit is 40*10-9, and the relative error of test results is 0.09%., The
      stability is better than 2.8%, which verify the feasibility of the instrument.

PMID- 30222266
TI  - Identification of Brake Fluid Brands, New and Used Brake Fluid with Discriminant
      Analysis Based on Near-Infrared Transmittance Spectroscopy.
AB  - Near-infrared transmittance spectroscopy was used to identify brake fluid brands,
      new and used brake fluid of each brand. The transmittance spectra of the new and
      used samples of 4 different brands of brake fluid, including BMW, Toyota, Volvo
      and Castrol were collected. PCA was conducted to the spectral data of the new
      samples of the four brake fluid and the spectral data of the new and used samples
      of each brand. The PCA scores scatter plot indicated that there were differences
      among the four brands of brake fluid, and there were also differences between new
      and used samples of each brand. Optimal wavelengths were selected for identifying
      different brands and new and used samples of each brand by loadings of PCA.
      Classification models were built using the optimal wavelength, including Partial
      least squares-discriminant analysis (PLS-DA), Linear discriminant analysis (LDA),
      Soft independent modeling of class analogy (SIMCA), k-nearest neighbor algorithm
      (KNN), Random forest (RF), Back propagation neural network (BPNN), Radial basis
      function neural network (RBFNN), Extreme learning machine (ELM), Support vector
      machine (SVM), Least-squares support vector machine (LS-SVM). All classification
      models obtained good performances, the classification accuracy of the calibration
      set and the prediction set are 100% for most models. Compared with other three
      brands, new and used samples of Castrol showed slighter difference, and KNN and
      LS-SVM models performed worse with classification accuracy under 100% in the
      calibration set. The overall results indicated that near-infrared transmittance
      combined with optimal wavenumber selection and classification methods could be
      used to identify brake fluid brands, new and used brake fluids, the results of
      this study could provide theoretical support for developing online and portable
      devices.

PMID- 30222267
TI  - Determination of Tomato's SSC and TS Based on Diffuse Transmittance Spectroscopy.
AB  - In order to meet the demands for rapid and safe nondestructive testing of fruit
      and vegetable quality,tomato detection system with a special circular light
      source was built based on the visible / near infrared diffuse transmission
      principle. Taking soluble solids content (SSC) and total sugar (TS) as the
      internal quality index, the prediction of 58 tomato samples was carried out by
      using this system. First, we collected the spectral data of four points for each
      tomato. Second, Savitzky-Golay smooth(SG-Smooth), standard normal variable
      transformation(SNV), multiplication scattering correction(MSC), first derivative
      (FD) and other methods were used to process the original spectral curve before
      the partial least squares regression(PLSR) model was established. Finally, we
      validated the established model. The results show that the correlation
      coefficient (r) of calibration and prediction of the SSC prediction model -are
      0.995 6 and 0.976 0 when using 10 point SG-smooth, and the root mean square error
      of calibration and prediction are 0.052 4% and 0.082 3%. The partial least square
      regression (PLSR)model, with respect to the first derivative (FD) spectra,
      provides better prediction performance for total sugar of tomato, with
      correlation coefficient (r) of calibration of 0.969 1 and 0.972 9, and
      prediction, root mean standard error of 0.423 8% and 0.454 9%. In the
      experimental verification of the prediction model, the relationship of SSC
      between predicted and true value is 0.985 5, root mean square error is 0.066 3
      degrees Brix, the relationship of TS between predicted and true value is 0.944 9
      while root mean square error is 0.571 5%. The results show that the content of
      soluble solids and total sugar in tomato can be realized by using visible / near
      infrared diffuse reflectance spectroscopy. It provides a real-time,
      nondestructive and rapid detection method for the evaluation of the internal
      quality of tomato, and provides a theoretical basis for its online grading.

PMID- 30222268
TI  - Raman Spectroscopic Study of the Structure of CaO-SiO2-Al2O3-Based Flux.
AB  - Due to the [Al] reaction with the CaO-SiO2-based mold flux used in the high-Al
      steels continuous casting processes, decreasing the SiO2 content is decreased and
      the Al2O3 content in mold flux is increased, thus converting the original CaO
      SiO2-based mold flux into a CaO-SiO2-Al2O3-based mold flux. This conversion of
      the mold fluxes can cause the problem of high-Al steels continuous casting.
      Hence, study on the structural characteristics of the CaO-SiO2-Al2O3- based mold
      flux can provide fundamental data to design optimum fluxes for high Al-containing
      steels. In this paper, the structural characteristics of the CaO-SiO2-based and
      CaO-SiO2-Al2O3-based flux were studied by Raman spectroscopy. The results have
      shown that, the CaO-SiO2-based flux was the silicate structure whose main micro
      structure units were Q0, Q1, Q2 and Q3. The network breakers prefer to
      depolymerize the silicate network in CaO-SiO2-Al2O3-based flux. While the CaO
      SiO2-Al2O3-based flux with low SiO2 content, the [AlO4] tetrahedron was entered
      the silicate network and the melt converted into the aluminosilicates structure,
      the formation of Al-O-Al linkages and Si-O-Al linkages increased the degree of
      disorder of network. The results of Li2O replace Na2O and CaO replace MgO have
      shown that the ions will influence the formation of [AlO4] tetrahedron linkages.
      CaF2 replace CaO shown that the polymerization degree of mold slag decreased
      first, and then increased with the content of CaF2 more than 13 mol%. So, the
      influences of the ions type and the ions content on the structure were both need
      considered while designing the CaO-SiO2-Al2O3-based flux.

PMID- 30222299
TI  - Raman and Visible-Near Infrared Spectra of Cu(InGa)Se2 Films.
AB  - Cu(InxGa1-x)Se2(CIGS) precursor films were prepared on ITO glass with
      potentiostatic electrodeposition. High quality CIGS films were obtained by
      selenization of the precursor films at high temperature in tubular furnace full
      of argon gas. X-ray diffraction (XRD), scanning electron microscopy (SEM) and UV
      Vis-NIR spectroscopy were used to characterize the structure, morphology,
      composition and Vis-NIR absorption of CIGS films, respectively. XRD results show
      the selenized CIGS films have a preferential orientation (112) with average
      crystallite of 24.7 nm. Raman spectroscopy reveals that the CIGS films are pure
      quaternaryphases with chalcopyrite structure, and without binary or ternary
      phases in the films. Vis-NIR measurements determine that the bandgap of CIGS
      increases with the increase of Ga concentration in the film. When the Ga
      concentration is 5.41%, its bandgap is about 1.11 eV, and the calculated ratio of
      Ga to (Ga+In) is 16.3%, which is less than the ratio of Ga to (Ga+In), 21.4%,
      measured by SEM. This indicates that crystallinity of CIGS filmsneeds to be
      further improved. All the measurements demonstratethat optimum ITO/CIGS has a
      promising application in bifacial solar cells. In this paper, we provide a
      newmethodtoelectrodeposit low cost CIGS precursor films and a new method
      forselenization ofthe precursor films at high temperature. As a result,
      theuniform and compact CIGS films with good adhesion on ITO are successfully
      fabricated by these methods. The above characterization show that we have
      obtained CIGS films with high crystallinity, near stoichiometry, few impurity
      phases and superior light absorption. Electrodeposition, like magnetron
      sputtering, is very suitable for large-scale industrial production. The research
      work in this paper is therefore important and considerable to massive production
      of electrodeposition of CIGS films.

PMID- 30222300
TI  - Spectroscopic Study on the Interaction of Human Cytoglobin with Copper(II) Ion.
AB  - Cytoglobin (Cygb), a recently discovered member of the vertebrate globin family,
      exhibits a traditional globin fold with a three-over-three alpha-helical
      sandwich. The interaction between copper(II) ion (Cu2+) and Cygb has been
      investigated by UV-Vis, fluorescence, synchronous fluorescence and circular
      dichroism (CD) spectra. Results showed that the absorption intensity of Cygb at
      280 nm increased and the intrinsic fluorescence of Cygb was quenched when Cu2+
      was added. This fluorescence quenching of Cygb has been proven that it belongs to
      static quenching. The synchronous fluorescence spectra indicated that there were
      small changes about the microenvironment of tryptophan residues and tyrosine
      residues; furthermore, the binding site of Cu2+ is closer to tryptophan residues
      than tyrosine residues. No obvious change was observed about the secondary
      structure of Cygb with the addition of Cu2+ from the CD spectra.

PMID- 30222301
TI  - Spectroscopic and Molecular Modeling Studies on Binding of Fleroxacin with Human
      Serum Albumin.
AB  - Fleroxacin (FLRX) is a new member of the class of fluoroquinolones, its effects
      on human serum albumin (HSA) and the mechanism of action are poorly understood,
      Especially, the secondary structural alterations of HSA induced by FLRX and the
      inner filter effect, which resulted in a spurious decrease in the observed
      fluorescence intensity and affected the binding parameters calculated from it are
      not considered. In this paper, binding of FLRX to HSA has been studied using
      multi-spectroscopy and molecular modeling methods. Fluorescence spectra revealed
      that the observed fluorescence quenching of HSA by FLRX was due to a 1?1 complex
      formation by a static quenching process with a constant of 105 L.mol-1. The
      thermodynamic parameters (DeltaH and DeltaS) were calculated to be -107.99 kJ.mol
      1 and -240.99 J.mol-1.K-1 via the Van't Hoff equation, which indicated that
      hydrogen bond and van der Waals force were the dominant intermolecular force.
      From the synchronous fluorescence, FT-IR and three dimensional fluorescence
      spectra, it was evident that the binding of FLRX to HSA induced a conformational
      change in the protein, and the alterations of secondary structure were
      quantitatively calculated by the evidence from FTIR spectra with reductions of
      alpha-helices of about 18.3%, decreases of beta-sheet structures of about 9.6%,
      and increases of beta-turn structures of about 18.0%. Site marker competitive
      experiments showed that phenylbutazone and FLRX shared a common binding site I
      corresponding to the subdomain II A of HSA. The binding details between FLRX and
      HSA were further confirmed by molecular docking studies, which revealed that FLRX
      was bound at subdomain II A through multiple interactions, such as hydrogen bond,
      hydrophobic and van der Waals, etc. The accurate and full basic data in the work
      is beneficial to clarify the binding mechanism of FLRX with HSA and is helpful
      for understanding its effect on protein function during the blood transportation
      process.

PMID- 30222302
TI  - Dendrite-Free Li Metal Anode for Rechargeable Li-SO2 Batteries Employing Surface
      Modification with a NaAlCl4-2SO2 Electrolyte.
AB  - Dendritic growth of a Li metal anode during cycling is one of major issues to be
      addressed for practical application of Li metal rechargeable batteries. Herein,
      we demonstrate that surface modification of Li metal with a Na-containing SO2
      electrolyte can be an effective way to prevent dendritic Li growth during cell
      operation. The surface-modified Li metal anode exhibited no dendritic deposits
      even under a high areal capacity (5 mA h cm-2) and a high current density (3 mA
      cm-2), whereas the unmodified anode showed typical filamentary Li deposition. The
      surface-modified Li metal anode also demonstrated significantly enhanced
      electrochemical performance, which could be attributed to the newly formed Na
      containing inorganic surface layer that exhibits uniform and dense properties.
      Consequently, surface modification with a Na-containing SO2 inorganic electrolyte
      is suggested as one of the most effective ways to realize a highly stable Li
      metal anode with dendrite-free Li deposition for Li metal-based rechargeable
      batteries.

PMID- 30222303
TI  - From Rapid Eye Movement Sleep Behavior Disorder to Parkinson's Disease: Possible
      Predictive Markers of Conversion.
AB  - Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) manifests as
      unpleasant dreams and dream-enacting behaviors during REM sleep. iRBD is
      currently recognized as a prodromal stage of Parkinson's disease (PD), and the
      majority of iRBD patients will develop PD. However, there is an approximately 10
      year interval between iRBD onset and established PD, which provides neurologists
      a window for intervention prior to irreversible neuron damage in prodromal PD
      patients. In this Review, we summarize possible predictive markers of PD in iRBD
      on clinical assessment, heredity, neuroimaging, and electrophysiology. We hope
      this summary can help researchers and clinical physicians better understand the
      risk factors for conversion from iRBD to PD and indicate directions for
      neuroprotective strategies and the prediction of disease progression.

PMID- 30222304
TI  - Exciplex Cohosts Employing Nonconjugated Linked Dicarbazole Donors for Highly
      Efficient Thermally Activated Delayed Fluorescence-Based Organic Light-Emitting
      Diodes.
AB  - Two new nonconjugated linked dicarbazole materials, dCzPSi and dCzPSO2, with high
      triplet energy were synthesized and characterized. dCzPSi and dCzPSO2 were
      adopted as unipolar host materials for the green thermally activated delayed
      fluorescence (TADF) emitter (4CzIPN) to achieve high-efficiency organic light
      emitting diodes (OLEDs). The electron-transporting acceptor, PO-T2T, was
      introduced to mix with dCzPSi and dCzPSO2 to give two new exciplex-forming
      systems that can improve the exciton formation propensity in the emitting layer.
      The relevant properties of these new exciplexes were characterized, and they were
      suggested as promising cohosts for the green TADF emitter, 4CzIPN. The
      characteristics of the devices employing single hosts (dCzPSi and dCzPSO2) and
      exciplex-forming cohosts (dCzPSi:PO-T2T and dCzPSO2:PO-T2T) were explored. The
      obtained results indicate that the Si-bridged dicarbazole compound dCzPSi
      outperforms its counterpart dCzPSO2 in which two carbazole groups are linked by
      an SO2 group. The device employed with the dCzPSi:PO-T2T cohost with 10 wt %
      4CzIPN achieved a low Von of 2.2 V and maximum efficiencies of 21.1% (external
      quantum efficiency), 56.4 cd A-1 (current efficiency), 59.1 lm W-1 (power
      efficiency), as compared to those (18.7%, 56.6 cd A-1, and 68.5 lm W-1) of the
      dCzPSO2:PO-T2T-hosted device. This work verifies the advantages of using a cohost
      that can form an exciplex for boosting the device efficiency with reduced
      efficiency roll-off of TADF-based OLEDs.

PMID- 30222305
TI  - Versatile Redox-Responsive Polyplexes for the Delivery of Plasmid DNA, Messenger
      RNA, and CRISPR-Cas9 Genome-Editing Machinery.
AB  - Gene therapy holds great promise for the treatment of many diseases, but clinical
      translation of gene therapies has been slowed down by the lack of safe and
      efficient gene delivery systems. Here, we report two versatile redox-responsive
      polyplexes (i.e., cross-linked and non-crosslinked) capable of efficiently
      delivering a variety of negatively charged payloads including plasmid DNA (DNA),
      messenger RNA, Cas9/sgRNA ribonucleoprotein (RNP), and RNP-donor DNA complexes
      (S1mplex) without any detectable cytotoxicity. The key component of both types of
      polyplexes is a cationic poly( N, N'-bis(acryloyl)cystamine- co
      triethylenetetramine) polymer [a type of poly( N, N'-bis(acryloyl)cystamine
      poly(aminoalkyl)) (PBAP) polymer] containing disulfide bonds in the backbone and
      bearing imidazole groups. This composition enables efficient encapsulation,
      cellular uptake, controlled endo/lysosomal escape, and cytosolic unpacking of
      negatively charged payloads. To further enhance the stability of non-crosslinked
      PBAP polyplexes, adamantane (AD) and beta-cyclodextrin (beta-CD) were conjugated
      to the PBAP-based polymers. The cross-linked PBAP polyplexes formed by host-guest
      interaction between beta-CD and AD were more stable than non-crosslinked PBAP
      polyplexes in the presence of polyanionic polymers such as serum albumin,
      suggesting enhanced stability in physiological conditions. Both cross-linked and
      non-crosslinked polyplexes demonstrated either similar or better transfection and
      genome-editing efficiencies, and significantly better biocompatibility than
      Lipofectamine 2000, a commercially available state-of-the-art transfection agent
      that exhibits cytotoxicity.

PMID- 30222306
TI  - Advanced P2-Na2/3Ni1/3Mn7/12Fe1/12O2 Cathode Material with Suppressed P2-O2 Phase
      Transition toward High-Performance Sodium-Ion Battery.
AB  - As a promising cathode material of sodium-ion battery, P2-type Na2/3Ni1/3Mn2/3O2
      (NNMO) possesses a theoretically high capacity and working voltage to realize
      high energy storage density. However, it still suffers from poor cycling
      stability mainly incurred by the undesirable P2-O2 phase transition. Herein, the
      electrochemically active Fe3+ ions are introduced into the lattice of NNMO,
      forming Na2/3Ni1/3Mn2/3- xFe xO2 ( x = 0, 1/24, 1/12, 1/8, 1/6) to effectively
      stabilize the P2-type crystalline structure. In such Fe-substituted materials,
      both Ni2+/Ni4+ and Fe3+/Fe4+ couples take part in the redox reactions, and the P2
      O2 phase transition is well restrained during cycling, as verified by ex situ X
      ray diffraction. As a result, the optimized Na2/3Ni1/3Mn7/12Fe1/12O2 (1/12-NNMF)
      has a long-term cycling stability with the fading rate of 0.05% per cycle over
      300 cycles at 5 C. Furthermore, the 1/12-NNMF delivers excellent rate
      capabilities (65 mA h g-1 at 25 C) and superior low-temperature performance (the
      capacity retention of 94% at -25  degrees C after 80 cycles) owing to the
      enhanced Na diffusion upon Fe doping, which is deduced by the studies of
      electrode kinetics. More significantly, the 1/12-NNMF also displays remarkable
      sodium-ion full-cell properties when merged with an LS-Sb@G anode, thus implying
      the possibility of their practical application.

PMID- 30222307
TI  - High-Performance Graphene-Based Natural Fiber Composites.
AB  - Natural fiber composites are attracting significant interest due to their
      potential for replacing synthetic composites at lower cost with improved
      environmental sustainability. However, natural fiber composites suffer from poor
      mechanical and interfacial properties. Here, we report coating of graphene oxide
      (GO) and graphene flakes (G) onto natural jute fibers to improve mechanical and
      interfacial properties. The coating of graphene materials onto jute fibers
      enhanced interfacial shear strength by ~236% and tensile strength by ~96% more
      than untreated fibers by forming either bonding (GO) or mechanical interlocking
      (G) between fibers and graphene-based flakes. This could lead to manufacturing of
      high-performance and environmental friendly natural fiber composites that can
      potentially replace synthetic composites in numerous applications, such as the
      automotive industry, naval vessels, household products, and even in the aerospace
      industry.

PMID- 30222308
TI  - Highly Conductive Fiber with Waterproof and Self-Cleaning Properties for Textile
      Electronics.
AB  - Major concerns in the development of wearable textile electronics are exposure to
      moisture and contamination. The exposure can cause electrical breakdown of the
      device and its interconnections, and thus continuous efforts have been made to
      fabricate textile electronics which are free from moisture and pollution. Herein,
      we developed a highly conductive and waterproof fiber with excellent electrical
      conductivity (0.11 Omega/cm) and mechanical stability for advanced interconnector
      components in wearable textile electronics. The fabrication process of the highly
      conductive fiber involves coating of a commercial Kevlar fiber with Ag
      nanoparticle-poly(styrene- block-butadiene- block-styrene) polymer composites.
      The fabricated fiber then gets treated with self-assembled monolayer (SAM)
      forming reagents, which yields waterproof and self-cleaning properties. To find
      optimal SAM-forming reagents, four different kinds of reagents involving 1-decane
      thiol (DT), 1 H,1 H,2 H,2 H-perfluorohexanethiol, 1 H,1 H,2 H,2 H
      perfluorodecyltrichlorosilane, 1 H,1 H,2 H,2 H-perfluodecanethiol (PFDT) were
      compared in terms of their thiol group and carbon chain lengths. Among the SAM
      forming reagents, the PFDT-treated conductive fiber showed superior waterproof
      and self-cleaning property, as well as great sustainability in the water with
      varying pH because of nanoscale roughness and low surface energy. In addition,
      the functionality of the conductive fiber was tested under mechanical compression
      via repeated washing and folding processes. The developed conductive fiber with
      waterproof and self-cleaning property has promising applications in the
      interconnector operated under water and textile electronics.

PMID- 30222309
TI  - Emerging Materials in Heterogeneous Electrocatalysis Involving Oxygen for Energy
      Harvesting.
AB  - Water-based renewable energy cycle involved in water splitting, fuel cells, and
      metal-air batteries has been gaining increasing attention for sustainable
      generation and storage of energy. The major challenges in these technologies
      arise due to the poor kinetics of the oxygen reduction reaction (ORR) and the
      oxygen evolution reactions (OER), besides the high cost of the catalysts.
      Attempts to address these issues have led to the development of many novel and
      inexpensive catalysts as well as newer mechanistic insights, particularly so in
      the last three-four years when more catalysts have been investigated than ever
      before. With the growing emphasis on bifunctionality, that is, materials that can
      facilitate both reduction and evolution of oxygen, this review is intended to
      discuss all major families of ORR, OER, and bifunctional catalysts such as
      metals, alloys, oxides, other chalcogenides, pnictides, and metal-free materials
      developed during this period in a single platform, while also directing the
      readers to specific and detailed review articles dealing with each family. In
      addition, each section highlights the latest theoretical and experimental
      insights that may further improve ORR/OER performances. The bifunctional
      catalysts being sufficiently new, no consensus appears to have emerged about the
      efficiencies. Therefore, a statistical analysis of their performances by
      considering nearly all literature reports that have appeared in this period is
      presented. The current challenges in rational design of these catalysts as well
      as probable strategies to improve their performances are presented.

PMID- 30222310
TI  - High-Performance Gas Sensor Using a Large-Area WS2 xSe2-2 x Alloy for Low-Power
      Operation Wearable Applications.
AB  - Two-dimensional (2D) transition-metal dichalcogenides (TMDCs) have attracted
      considerable attention as promising building blocks for a new generation of gas
      sensing devices because of their excellent electrical properties, superior
      response, flexibility, and low-power consumption. Owing to their large surface-to
      volume ratio, various 2D TMDCs, such as MoS2, MoSe2, WS2, and WSe2, have
      exhibited excellent gas-sensing characteristics. However, exploration toward the
      enhancement of TMDC gas-sensing performance has not yet been intensively
      addressed. Here, we synthesized large-area uniform WS2 xSe2-2 x alloys for room
      temperature gas sensors. As-synthesized WS2 xSe2-2 x alloys exhibit an
      elaborative composition control owing to their thermodynamically stable
      sulfurization process. Further, utilizing uniform WS2 xSe2-2 x alloys over a
      large area, we demonstrated improved NO2-sensing performance compared to WSe2 on
      the basis of an electronic sensitization mechanism. The WS0.96Se1.04 alloy gas
      sensor exhibits 2.4 times enhanced response for NO2 exposure. Further, we
      demonstrated a low-power wearable NO2-detecting wristband that operates at room
      temperature. Our results show that the proposed method is a promising strategy to
      improve 2D TMDC gas sensors and has a potential for applications in advanced gas
      sensing devices.

PMID- 30222311
TI  - Multimetallic Lanthanide Complexes: Using Kinetic Control To Define Complex
      Multimetallic Arrays.
AB  - Kinetically inert lanthanide complexes are proving to be highly effective
      building blocks for the preparation of complex heterometallic architectures,
      allowing complete control of metal ion domains, which cannot be achieved under
      thermodynamic control. Kinetic stability may render perceivable labile
      coordination bonds more durable than several types of covalent interactions. For
      complexes in clinical use, the significance of kinetic stability cannot be
      overstated, and this Account treats the topic accordingly. Kinetically inert
      complexes can be used as building blocks for elaborate synthesis. For instance,
      it is now possible to prepare heterometallic lanthanide complexes containing two
      or more different lanthanide ions by linking kinetically robust complexes
      together. This approach can yield bimetallic (f-f' or d-f) and trimetallic (f-f'
      f") lanthanide complexes. In this Account, we describe our studies exploiting the
      slow dissociation of lanthanide complexes derived from 1,4,7,10-tetraazadodecane
      1,4,7,10-tetraacetic acid (DOTA) related ligands to link complexes together
      through synthetic manipulation of pendent groups on the ligand skeleton or
      through coordination of bridging donor groups to a d-block metal center. In the
      course of this work, we have developed a variety of such methods, ranging from
      peptide coupling and diazotization to Ugi and click chemistry and have also
      explored the use of alternative strategies that combine orthogonal protecting
      group chemistry with sequential complexation of different lanthanide ions or that
      use self-assembly to deliver well-defined multimetallic systems. These well
      defined bimetallic systems also have considerable scope for exploitation. Since
      the earliest studies, it has been clear that there is potential for application
      in the burgeoning field of molecular imaging. Heterometallic lanthanide complexes
      can be used as single-molecule bimodal imaging agents through incorporation of
      MRI active and luminescent components. Alternatively, conventional luminescence
      methods can be exploited in conjunction with lanthanide luminescence. In the
      simplest cases, a single lanthanide can be used to achieve a switchable response
      in combination with a transition metal complex. Bimetallic f-f' complexes allow
      the full potential of the approach to be realized in systems in which one
      lanthanide responds to changes in the concentration of an analyte, while a second
      lanthanide center can be used to define the concentration of the probe itself.
      This offers a new solution to the old dichotomy of ratiometric imaging that can
      potentially be applied widely.

PMID- 30222312
TI  - Studies on the Activity of Selected Highly Lipophilic Compounds toward hGAT1
      Inhibition. Part II.
AB  - In this paper, we describe the latest results involving molecular modeling and
      pharmacodynamic studies of the selected highly lipophilic compounds acting by
      human GABA transporter 1 (hGAT1) inhibition. The chemical interaction of 17 GABA
      analogues with a model of hGAT1 is described using the molecular docking method.
      The biological role of GAT1 is related to the regulation of GABA level in the
      central nervous system and GAT1 inhibition plays an important role in the control
      of seizure threshold. To confirm that GAT1 can be also a molecular target for
      drugs used to treat other neurological and psychiatric diseases (e.g., pain and
      anxiety), in the in vivo part of this study, potential antinociceptive and
      anxiolytic-like properties of tiagabine, a selective GAT1 inhibitor, are
      described.

PMID- 30222313
TI  - Controllable Fabrication of Graphene and Related Two-Dimensional Materials on
      Liquid Metals via Chemical Vapor Deposition.
AB  - Due to the confinement of the charge, spin, and heat transport in the plane,
      graphene and related two-dimensional (2D) materials have been demonstrated to own
      many unique and excellent properties and witnessed many breakthroughs in physics.
      They show great application potential in many fields, especially for electronics
      and optoelectronics. However, a bottleneck to widespread applications is precise
      and reliable fabrication, in which the control of the layer number and domain
      assembly is the most basic and important since they directly determine the
      qualities and properties of 2D materials. The chemical vapor deposition (CVD)
      strategy was regarded as the frontrunner to achieve this target, and the design
      of the catalytic substrate is of great significance since it has the most direct
      influence on the catalysis and mass transfer, which can be the most essential
      elemental steps. In recent years, as compared to traditional solid metal
      catalysts, the emergence of liquid metal catalysts has brought a brand-new
      perspective and contributes to a huge change and optimization in the fabrication
      of 2D materials. On one hand, strictly self-limited growth behavior is discovered
      and is robust to the variation of the growth parameters. The atoms in the liquid
      metal tend to move intensely and arrange in an amorphous and isotropic way. The
      liquid surface is smooth and isotropic, and the vacancies in the fluidic liquid
      phase enable the embedding of heteroatoms. The phase transition from liquid to
      solid will facilitate the unique control of the mass-transfer path, which can
      trigger new growth mechanisms. On the other hand, the excellent rheological
      properties of liquid metals allow us to explore self-assembly of the 2D materials
      grown on the surface, which can activate new applications based on the derived
      collective properties, such as the integrated devices. Indeed, liquid metals show
      many unique behaviors in the catalytic growth and assembly of 2D materials. Thus,
      this Account aims to highlight the controllable fabrication of graphene and
      related 2D materials on liquid metals. By utilizing the phase transition of
      liquid metals, the segregation of precursors in the bulk can be controlled,
      leading to self-limited growth. By utilizing the fluidity of the liquid metals,
      2D material crystals can achieve self-assembly on their surface, including
      oriented stitching, ordered assembly, and heterostacking, which enables the
      creation of new multilevel or hybrid structures, leading to property and function
      extension and even the emergence of new physics. Finally, the unique liquid
      characteristic of liquid metals can also offer us new ideas about the transfer
      process. By utilizing the shear transformation of liquid metals, the direct
      sliding transfer of 2D materials onto arbitrary substrates can be realized. The
      research concerning the self-limited growth, self-assembly, and sliding transfer
      of 2D materials on liquid metals is just raising the curtain on the behavioral
      study of 2D materials on liquid metals. We believe these primary technology
      developments revealed by liquid metals will establish a solid foundation for both
      fundamental research and practical application of 2D materials.

PMID- 30222314
TI  - Plug-and-Play Nanorization of Coarse Black Phosphorus for Targeted Chemo
      photoimmunotherapy of Colorectal Cancer.
AB  - Because of their extraordinary physical properties and biocompatibility, black
      phosphorus (BP) nanosheets (NSs) have been intensively employed in chemo
      phototherapies, such as plasmonic inorganic nanoparticles or graphene NSs, over
      the past few years. However, most biomedical studies using BP NSs are only
      concerned with the optical property of BP NSs to repeatedly demonstrate chemo
      phototherapeutic efficacies, although BP NSs have different properties from
      inorganic nanoparticles or graphene NSs, such as corrugated crystal structure,
      hydrophilicity, and biodegradability. Moreover, it is still a challenging issue
      to efficiently fabricate uniform BP NSs for clinical translation because of the
      top-down nature of fabrication, despite the easy preparation of coarse BP flakes.
      It is thus essential to explore their most suitable bioapplications as well as
      suggest an easy-to-access strategy to produce uniform BP NSs for realization as
      advanced therapeutic materials. To rationalize these issues, this report
      introduces a plug-and-play nanorization, ultrasonic bubble bursting, of coarse BP
      flakes for continuous BP NS production, and the resulting uniform NSs (~40 nm
      lateral dimension, ~0.15 polydispersity index) were used as base materials to
      load drug (doxorubicin), targeting agent (chitosan-polyethylene glycol), and
      cancer growth inhibitor (programmed death ligand 1 and small interfering RNA) for
      achieving efficacious chemo-photoimmunotherapy of colorectal cancer.

PMID- 30222315
TI  - All-Perovskite Emission Architecture for White Light-Emitting Diodes.
AB  - We demonstrate all-perovskite light-emitting diodes (PeLEDs) with white emission
      on the basis of simultaneously solving a couple of issues including the ion
      exchanges between different perovskites, solvent incompatibility in the solution
      process of stacking different perovskites and carrier transport layers, as well
      as the energy level matching between each layer in the whole device. The PeLEDs
      are built with a two-dimensional (CH3CH2CH2NH3)2CsPb2I7 perovskite that emits red
      light, CsPb(Br,Cl)3 quantum dots that emit a cyan color, and an interlayer
      composed of bis(1-phenyl-1H-benzo[ d]imidazole)phenylphosphine oxide (BIPO) and
      poly(4-butylphenyl-diphenyl-amine) (Poly-TPD). The interlayer is designed to
      realize desirable white electroluminescence by tuning the electron and hole
      transportation and distribution in-between multilayers. With this PeLED
      configuration, we achieve the typical white light with chromaticity coordinates
      of (0.32, 0.32) in Commission Internationale de L'Eclairage (CIE) 1931 color
      space diagram and steady CIE coordinates in a wide range of driving current
      densities (from 2.94 to 59.29 mA/cm2). Consequently, our work, as the starting
      point for future research of all-perovskite white PeLEDs, will contribute to the
      future applications of PeLEDs in lighting and display. In addition, we believe
      that the proposed material and all-perovskite concept will leverage the design
      and development of more perovskite-based devices.

PMID- 30222316
TI  - Comparison of Direct and Indirect Laser Ablation of Metallized Paper for
      Inexpensive Paper-Based Sensors.
AB  - In this work, we present a systematic study of laser processing of metallized
      papers (MPs) as a simple and scalable alternative to conventional
      photolithography-based processes and printing technologies. Two laser-processing
      methods are examined in terms of selectivity for the removal of the conductive
      aluminum film (25 nm) of an MP substrate; these processes, namely direct and
      indirect laser ablation (DLA and ILA), operate at wavelengths of 1.06 MUm
      (neodymium-doped yttrium aluminum garnet) and 10.6 MUm (CO2), respectively. The
      required threshold energy for each laser processing method was systematically
      measured using electrical, optical, and mechanical characterization techniques.
      The results of these investigations show that the removal of the metal coating
      using ILA is only achieved through partial etching of the paper substrate. The
      ILA process shows a narrow effective set of laser settings capable of removing
      the metal film while not completely burning through the paper substrate. By
      contrast, DLA shows a more defined and selective removal of the aluminum layer
      without damaging the mechanical and natural fibular structure of the paper
      substrate. Finally, as a proof of concept, interdigitated capacitive moisture
      sensors were fabricated by means of DLA and ILA onto the MP substrate, and their
      performance was assessed in the humidity range of 2-85%. The humidity sensitivity
      results show that the DLA sensors have a superior humidity sensing performance
      compared to the ILA sensors. The observed behavior is attributed to the higher
      water molecule absorption and induced capillary condensation within the intact
      cellulose network resulting from the DLA process (compared to the damaged one
      from the ILA process). The DLA process of MP should enable scalable production of
      low-cost, paper-based physical and chemical sensing systems for potential use in
      point-of-care diagnostics and food packaging.

PMID- 30222317
TI  - Light-Emitting Plexciton: Exploiting Plasmon-Exciton Interaction in the
      Intermediate Coupling Regime.
AB  - The interaction between plasmons in metal nanostructures and excitons in layered
      materials attracts recent interests due to its fascinating properties inherited
      from the two constituents, e.g., the high tunability on its spectral or spatial
      properties from the plasmonic component, and the large optical nonlinearity or
      light emitting properties from the excitonic counterpart. Here, we demonstrate
      light-emitting plexcitons from the coupling between the neutral excitons in
      monolayer WSe2 and highly confined nanocavity plasmons in the nanocube-over
      mirror system. We observe, simultaneously, an anticrossing dispersion curve of
      the hybrid system in the dark-field scattering spectrum and a 1700 times
      enhancement in the photoluminescence. We attribute the large photoluminescence
      enhancement to the increased local density of states by both the plasmonic and
      excitonic constituents in the intermediate coupling regime. In addition,
      increasing the confinement of the hybrid systems is achieved by shrinking down
      the size of the hot spot within the gap between the nanocube and the metal film.
      Numerical calculations reproduce the experimental observations and provide the
      effective number of excitons taking part in the interaction. This highly compact
      system provides a room temperature testing platform for quantum cavity
      electromagnetics at the deep subwavelength scale.

PMID- 30222318
TI  - Facet-Mediated Adsorption and Molecular Fractionation of Humic Substances on
      Hematite Surfaces.
AB  - Interactions between dissolved organic matter (DOM) and iron oxyhydroxides have
      important environmental and geochemical implications. The present study employed
      two hematite nanocrystals to investigate the adsorption and molecular
      fractionation of two typical humic substances (HSs) using electrospray ionization
      coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT
      ICR-MS). Hematite with a predominant exposure of {100} facets induced more
      pronounced adsorption and molecular fractionation of HSs than {001} facets,
      indicating that the interfacial adsorptive fractionation process of HSs was
      mediated by exposed facets of hematite. Further exploration of the surface OH
      groups of the two hematite nanocrystals confirms that the facet-mediated
      molecular fractionation of HSs was attributable to the abundance of singly iron
      atom coordinated -OH sites on the hematite surfaces. Molecules with a high
      oxidation state and high aromaticity such as oxidized black carbon, polyphenol
      like, and tannic-like compounds preferentially formed ligand-exchange complexes
      with singly coordinated -OH groups on the hematite surfaces, inducing the
      selective binding and molecular fractionation of HSs at the mineral-water
      interface. These results demonstrate that singly iron-atom coordinated -OH sites
      determine DOM adsorption and mediate molecular fractionation on hematite
      surfaces, and this contributes substantially to our understanding of the
      molecular mechanisms of iron oxyhydroxide-mediated molecular exchange of DOM in
      soils and/or sediments.

PMID- 30222319
TI  - Paper-Based Analytical Methods for Smartphone Sensing with Functional
      Nanoparticles: Bridges from Smart Surfaces to Global Health.
AB  - In this Feature, the most recent developments as well as "pros and cons" in
      smartphone sensing, which have been developed using various functional
      nanoparticles in paper-based sensing systems, will be discussed. Additionally,
      smart phone sensing and POC combination as a potential tool that opens a gate for
      knowledge flow "from lab scale data to public use" will be evaluated.

PMID- 30222320
TI  - Reactivity of Tetrahalo- and Difluorodiboranes(4) toward Lewis Basic Platinum(0):
      Bis(boryl), Borylborato, and Doubly Boryl-Bridged Platinum Complexes.
AB  - The reaction of the tetrahalodiboranes(4) B2F4, B2Cl4, and B2Br4 with a Lewis
      basic platinum(0) complex led to the isolation of the cis-bis(difluoroboryl)
      complex cis-[(Cy3P)2Pt(BF2)2] (1) and the novel borylborato complexes trans
      [(Cy3P)2Pt{B(X)-BX3}] (2, X = Cl; 3, X = Br), respectively. The trans influence
      of the borylborato group was found to be one of the strongest ever observed
      experimentally. Furthermore, the reactivity of little-explored
      diaryldifluorodiboranes(4) F2B-BMes2 and the new derivative F2B-BAn2 (An = 9
      anthryl) toward a range of platinum(0) complexes was investigated. Reactions with
      relatively nonbulky platinum(0) complexes led to the formation of unsymmetrical
      cis-bis(boryl) complexes cis-[(R3P)2Pt(BF2)(BMes2)] (6, R = Me; 7, R = Et) as
      well as the first example of a fourfold-unsymmetrical bis(boryl) complex,
      [(Me3P)(Cy3P)Pt(BF2)(BMes2)] (12). The use of a more bulky Pt complex provided
      access to the unprecedented dinuclear bis(boryl) complexes [{( iPr3P)Pt}2(MU
      BF2)(MU-BAr2)] (8, Ar = Mes; 9, Ar = An), which feature two different MU2
      bridging boryl ligands.

PMID- 30222321
TI  - Catalyst-Controlled Selective Functionalization of Unactivated C-H Bonds in the
      Presence of Electronically Activated C-H Bonds.
AB  - A new chiral dirhodium tetracarboxylate catalyst, Rh2( S-2-Cl-5-BrTPCP)4, has
      been developed for C-H functionalization reactions by means of donor/acceptor
      carbene intermediates. The dirhodium catalyst contains four ( S)-1-(2-chloro-5
      bromophenyl)-2,2-diphenylcyclopropane-1-carboxylate ligands, in which all four 2
      chloro-5-bromophenyl groups are on the same face of the catalyst, leading to a
      structure, which is close to C4 symmetric. The catalyst induces highly site
      selective functionalization of remote, unactivated methylene C-H bonds even in
      the presence of electronically activated benzylic C-H bonds, which are typically
      favored using earlier established dirhodium catalysts, and the reactions proceed
      with high levels of diastereo- and enantioselectivity. This C-H functionalization
      method is applicable to a variety of aryl and heteroaryl derivatives.
      Furthermore, the potential of this methodology was illustrated by sequential C-H
      functionalization reactions to access the macrocyclic core of the
      cylindrocyclophane class of natural products.

PMID- 30222322
TI  - Synthesis and Characterization of Electroconductive PHA- graft-Graphene
      Nanocomposites.
AB  - With increasing demand of environmentally friendly materials, development on
      biobased polymers such as polyhydroxyalkanoate (PHA) is indispensable. An
      unsaturated PHA, namely, poly(3-hydroxydodecanoate- co-3-hydroxy-9-decenoate),
      short as P(3HDD- co-3H9D), provides possibilities for functionalization. Two
      different strategies are explored for synthesis of PHA- graft-graphene
      nanocomposites with graphene content ranging from 0.2 to 1.5 wt %. Chemical
      structures of intermediates and products were confirmed by Fourier transform
      infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). Uniform
      dispersion of graphene was observed in formed PHA nanocomposites under scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), and atomic
      force microscopy (AFM). PHA- graft-graphene nanocomposites exhibited higher
      thermal degradation temperature and enhanced electricity conductivity compared
      with that of neat PHA. Moreover, lower critical filling content and lower
      electrical resistivity at same graphene content demonstrated enhanced electrical
      conductivity of PHA- graft-graphene nanocomposites compared with previously
      reported blends. The lowest electrical resistivity was 2 Omega.m in sample PHA-
      graft-graphene nanocomposites with approximately 1.5 wt % graphene content.

PMID- 30222323
TI  - Application of Direct Analysis in Real Time-High Resolution Mass Spectrometry to
      Investigations of Induced Plant Chemical Defense Mechanisms-Revelation of
      Negative Feedback Inhibition of an Alliinase.
AB  - Several plants of agricultural and medicinal importance utilize defense chemistry
      that involves deployment of highly labile, reactive, and lachrymatory
      organosulfur molecules. However, this chemistry is difficult to investigate
      because the compounds are often short-lived and prone to degradation under the
      conditions required for analysis by common analytical techniques. This issue has
      complicated efforts to study the defense chemistry of plants that exploit the use
      of sulfur in their defense arsenals. This work illustrates how direct analysis in
      real time-high resolution mass spectrometry (DART-HRMS) can be used to track
      organosulfur defense compound chemistry under mild conditions. Petiveria alliacea
      was used as a model plant that exploits the enzyme alliinase to generate induced
      organosulfur compounds in response to herbivory. Tracking of the organosulfur
      compounds it produces and quantifying them by DART-HRMS using isotopically
      labeled analogues revealed a feedback inhibition loop through which the
      activities of the alliinase are stymied shortly after their activation. The
      results show that the downstream thiosulfinate products petivericin (100 MUM) and
      pyruvate (8.4 mM) inhibit alliinase activity by 60% and 29%, respectively, after
      1 h, and a mixture of the two inhibited alliinase activity by 65%. By 2 h,
      alliinase activity in the presence of these alliinase-derived products had ceased
      completely. Because thiosulfinate, pyruvate, and lachrymatory sulfine compounds
      are produced via the same alliinase-derived sulfenic acid intermediate, the
      inhibition of alliinase activity by increasing concentrations of downstream
      products shows how production of these defense compounds is modulated in real
      time in response to a tissue breach. These findings provide a framework within
      which heretofore unexplained phenomena observed in the defense chemistry of P.
      alliacea, onion, garlic, and other plants can be explained, as well as an
      approach by which to track labile compounds and enzymatic activity by DART-HRMS.

PMID- 30222324
TI  - Facial and Meridional Isomers of Tris(bidentate) Ir(III) Complexes: Unravelling
      Their Different Excited State Reactivity.
AB  - The use of tris(bidentate) Ir(III) complexes as light active components in
      phosphorescent organic light-emitting diodes (PhOLEDs) is currently the state-of
      the-art technology to attain long-lasting and highly performing devices. Still,
      further improvements of their operational lifetimes are required for their
      practical use in lighting and displays. Facial/meridional stereoisomerism of the
      tris(bidentate) Ir(III) architectures strongly influences their emissive
      properties and thereto their PhOLEDs performances and operational device
      stabilities. This work underpins at the first-principles level the different
      excited state reactivities of facial and meridional stereoisomers of a series of
      tris(bidentate) Ir(III) complexes, which is found to originate in the presence of
      distinct triplet metal-centered (3MC) deactivation pathways. These deactivation
      pathways are herein presented for the first time for the meridional isomers.
      Finally, we propose some phosphor design strategies.

PMID- 30222325
TI  - Hydrogen-Bonding Interactions at the DNA Terminus Promote Extension from
      Methylguanine Lesions by Human Extender DNA Polymerase zeta.
AB  - Chemically induced DNA lesions can become DNA replication substrates that are
      bypassed by low-fidelity DNA polymerases. Following nucleotide misinsertion
      opposite a DNA lesion, the extension step can contribute to preserving such
      errors and lead to genomic instability and cancer. DNA polymerase zeta, a B
      family polymerase, is proficient as an extender polymerase that catalyzes
      elongation; however, the chemical factors that impact its DNA replication are not
      understood. This study addresses the question of how DNA polymerase zeta achieves
      extension by examining the ability of recombinant human DNA polymerase zeta to
      extend from a series of methylated guanine lesions. The influence of H-bonding
      was examined by placing structurally altered nucleoside analogues and canonical
      bases opposite G, O6-MeG, N1-MeG, and N2-MeG. We determined that terminal base
      pairs with the highest proclivity for H-bonding were most efficiently extended in
      both primer extension assays and steady-state kinetic analysis. In contrast, when
      no H-bonding was possible at the DNA terminus, the least efficient steady-state
      kinetics were observed. To evaluate H-bonding protein minor groove interactions
      that may underlie this phenomenon, we performed computational modeling with
      Escherichia coli DNA polymerase II, a homologue for DNA polymerase zeta. The
      modeling data together with the primer extension assays demonstrate the
      importance of having a carbonyl group on the primer strand that can interact with
      a lysine residue found to be conserved in many B-family polymerases, including
      human Pol zeta. These data provide a model whereby interbase H-bonding
      interactions at the DNA terminus promote lesion bypass and extension by human DNA
      polymerase zeta.

PMID- 30222326
TI  - Low-Cost Passive Sampling Device with Integrated Porous Membrane Produced Using
      Multimaterial 3D Printing.
AB  - Multimaterial 3D printing facilitates the rapid production of complex devices
      with integrated materials of varying properties and functionality. Herein,
      multimaterial fused deposition modeling (MM-FDM) 3D printing was applied to the
      fabrication of low-cost passive sampler devices with integrated porous membranes.
      Using MM-FDM 3D printing, the device body was produced using black polylactic
      acid, with Poro-Lay Lay-Felt filament used for the printing of the integrated
      porous membranes (rubber-elastomeric polymer, porous after removal of a water
      soluble poly(vinyl alcohol) component). The resulting device consisted of two
      interlocking circular frames, each containing the integrated membrane, which
      could be efficiently sealed together without the need for additional O-rings, and
      prevented loss of enclosed microparticulate sorbent. Scanning electron microscopy
      (SEM) analysis of the purified composite filament confirmed the porous properties
      of the material, an average pore size of ~30 nm. The printed passive samplers
      with various membrane thicknesses, including 0.5, 1.0, and 1.5 mm, were evaluated
      for their ability to facilitate the extraction of atrazine as the model solute
      onto the internal sorbent, under standard conditions. Gas chromatography-mass
      spectrometry was used to determine the uptake of atrazine by the device from
      standard water samples and also to evaluate any chemical leaching from the
      printed materials. The sampler with 0.5 mm thick membrane showed the best
      performance with 87% depletion and a sampling rate of 0.19 Ld-1 ( n = 3, % RSD =
      0.59). The results obtained using these printed sampling devices with integrated
      membranes were in close agreement to devices fitted with a standard poly(ether
      sulfone) membrane.

PMID- 30222327
TI  - Low-Cost and Rapid-Production Microfluidic Electrochemical Double-Layer
      Capacitors for Fast and Sensitive Breast Cancer Diagnosis.
AB  - This technical note describes a new microfluidic sensor that combines low-cost
      (USD $0.97) with rapid fabrication and user-friendly, fast, sensitive, and
      accurate quantification of a breast cancer biomarker. The electrodes consisted of
      cost-effective bare stainless-steel capillaries, whose mass production is already
      well-established. These capillaries were used as received, without any surface
      modification. Microfluidic chips containing electrical double-layer capillary
      capacitors (MUEDLC) were obtained by a cleanroom-free prototyping that allows the
      fabrication of dozens to hundreds of chips in 1 h. This sensor provided the
      successful quantification of CA 15-3, a biomarker protein for breast cancer, in
      serum samples from cancer patients. Antibody-anchored magnetic beads were
      utilized for immunocapture of the marker, and then, water was added to dilute the
      protein. Next, the CA 15-3 detection (<2 min) was made without using redox
      probes, antibody on electrode (sandwich immunoassay), or signal amplification
      strategies. In addition, the capacitance tests eliminated external pumping
      systems and precise volumetric sampling steps, as well as presented low sample
      volume (5 MUL) and high sensitivity using bare capillaries in a new design for
      double-layer capacitors. The achieved limit-of-detection (92.0 MUU mL-1) is lower
      than that of most methods reported in the literature for CA 15-3, which are based
      on nanostructured electrodes. The data shown in this technical note support the
      potential of the MUEDLC toward breast cancer diagnosis even at early stages. We
      believe that accurate analyses using a simple sample pretreatment such as
      magnetic field-assisted immunocapture and cost-effective bare electrodes can be
      extended to quantify other cancer biomarkers and even biomolecules by changing
      the biorecognition element.

PMID- 30222328
TI  - Uranyl Complexes with Aroylbis( N, N-dialkylthioureas).
AB  - The reaction of isophthaloylbis( N, N-diethylthiourea), H2L1, with
      UO2(CH3COO)2.2H2O and NEt3 as a supporting base gives a tetranuclear, anionic
      complex of the composition [{UO2(L1)}4(OAc)2]2-, in which the uranyl ions are S,
      O-chelate bonded. Each two of them are additionally linked by an acetato ligand.
      Similar reactions of various uranyl starting materials (uranyl acetate, uranyl
      nitrate, (NBu4)2[UO2Cl4]) with corresponding pyridine-centered ligands (pyridine
      2,6-dicarbonylbis( N, N-dialkylthioureas), H2L2) yield mononuclear, neutral
      compounds, in which the thiourea derivatives are coordinated as S, N, N, N, S
      five-dentate chelators. The equatorial coordination spheres of the formed
      hexagonal bipyramidal complexes [UO2(L2)(solv)] are completed by solvent ligands
      (H2O, MeOH, or DMF). Attempted reactions without a supporting base result in
      decomposition of the organic ligands and the formation of hexanuclear uranyl
      complexes with pyridine-2,6-dicarboxylato ligands, while the use of an excess of
      base results in condensation and the formation of dinuclear [{UO2(L2)(MU-OMe)}2]2
      complexes. A stable complex of the composition [UO2(L3)] results from reactions
      of common uranyl starting materials with 2,2'-bipyridine-6,6'-dicarbonylbis( N, N
      diethylthiourea) (H2L3). The equatorial coordination sphere of the neutral,
      hexagonal bipyramidal complex is occupied by an SN4S donor atom set, which is
      provided by the hexadentate organic ligand. While the uranium complexes with
      {L1}2- and {L2}2- are labile and rapidly decompose in acidic solutions, [UO2(L3)]
      is stable over a wide pH range, and the ligand readily extracts uranyl ions from
      aqueous solutions into organic solvents.

PMID- 30222329
TI  - Stabilization of NaNO3-Promoted Magnesium Oxide for High-Temperature CO2 Capture.
AB  - NaNO3-promoted MgO sorbents are known to achieve enhanced CO2 sorption uptake but
      fail to maintain their capacity after multiple sorption-regeneration cycles. In
      this study, commercially available hydrotalcites (Pural Mg30, Pural Mg70, and
      synthetic hydrotalcite) were used as stabilizers for NaNO3-impregnated MgO
      (MgONaNO3) sorbents to improve their cyclic stability. Results show that the Mg30
      stabilized MgONaNO3 attained higher and stable overall CO2 sorption performance
      as compared to bare MgONaNO3 after multiple sorption cycles. XRD analyses reveal
      that the hydrotalcites act as templates for MgCO3 by restricting the formation of
      large and nonuniform product crystallites. Furthermore, CO2-TPD results show that
      the hydrotalcites cause a change in the basic sites of the sorbent, which may be
      attributed to its high interaction with both MgO and NaNO3. This interaction
      becomes stronger as cycles proceed due to the structural rearrangements
      occurring, thus contributing to the stable behavior of the sorbents. However,
      these characteristics were not found on MgONaNO3 and the alpha-Al2O3-stabilized
      samples, thus proving the unique ability of hydrotalcites. From these results, we
      then derived the formation scheme of MgCO3 on the hydrotalcite-stabilized
      sorbents. This study presents a simple yet effective method of improving the
      stability of molten salt-promoted sorbents with promising potential for
      industrial use.

PMID- 30222330
TI  - ENDOR Characterization of (N2)FeII(MU-H)2FeI(N2)-: A Spectroscopic Model for N2
      Binding by the Di-MU-hydrido Nitrogenase Janus Intermediate.
AB  - The biomimetic diiron complex 4-(N2)2, featuring two terminally bound Fe-N2
      centers bridged by two hydrides, serves as a model for two possible states along
      the pathway by which the enzyme nitrogenase reduces N2. One is the Janus
      intermediate E4(4H), which has accumulated 4[e-/H+], stored as two [Fe-H-Fe]
      bridging hydrides, and is activated to bind and reduce N2 through reductive
      elimination (RE) of the hydride ligands as H2. The second is a possible RE
      intermediate. 1H and 14N 35 GHz ENDOR measurements confirm that the formally
      Fe(II)/Fe(I) 4-(N2)2 complex exhibits a fully delocalized, Robin-Day type-III
      mixed valency. The two bridging hydrides exhibit a fully rhombic dipolar tensor
      form, T ~ [- t, + t, 0]. The rhombic form is reproduced by a simple point-dipole
      model for dipolar interactions between a bridging hydride and its "anchor" Fe
      ions, confirming validity of this model and demonstrating that observation of a
      rhombic form is a convenient diagnostic signature for the identification of such
      core structures in biological centers such as nitrogenase. Furthermore,
      interpretation of the 1H measurements with the anchor model maps the g tensor
      onto the molecular frame, an important function of these equations for
      application to nitrogenase. Analysis of the hyperfine and quadrupole coupling to
      the bound 14N of N2 provides a reference for nitrogen-bound nitrogenase
      intermediates and is of chemical significance, as it gives a quantitative
      estimate of the amount of charge transferred between Fe and coordinated N, a key
      element in N2 activation for reduction.

PMID- 30222331
TI  - Dicopper(I) Complexes Incorporating Acetylide-Functionalized Pyridinyl-Based
      Ligands: Synthesis, Structural, and Photovoltaic Studies.
AB  - Heteroaryl incorporated acetylide-functionalized pyridinyl ligands (L1-L6) with
      the general formula Py-C=C-Ar (Py = pyridine and Ar = thiophene-2-yl, 2,2' 
      bithiophene]-5-yl, 2,2' :5',2" -terthiophene]-5-yl, thieno[2,3- b]thiophen-2-yl,
      quinoline-5-yl, benzo[c][1,2,5]thiadiazole-5-yl) have been synthesized by
      Pd(0)/Cu(I)-catalyzed cross-coupling reaction of 4-ethynylpyridine and the
      respective heteroaryl halide. Ligands L1-L6 were isolated in respectable yields
      and characterized by microanalysis, IR spectroscopy, 1H NMR spectroscopy, and ESI
      MS mass spectrometry. A series of dinuclear Cu(I) complexes 1-10 have been
      synthesized by reacting L1-L6 with CuI and triphenylphosphine (PPh3) (R1) or with
      an anchored phosphine derivative, 4-(diphenylphosphino) benzoic acid (R2)/2
      (diphenylphosphino)benzenesulfonic acid (R3), in a stoichiometric ratio. The
      complexes are soluble in common organic solvents and have been characterized by
      analytical, spectroscopic, and computational methods. Single-crystal X-ray
      structure analysis confirmed rhomboid dimeric structures for complexes 1, 2, 4,
      and 5, and a polymeric structure for 6. Complexes 1-6 showed oxidation potential
      responses close to 0.9 V vs Fc0/+, which were chemically irreversible and are
      likely to be associated with multiple steps and core oxidation. Preliminary
      photovoltaic (PV) results of these new materials indicated moderate power
      conversion efficiency (PCE) in the range of 0.15-1.56% in dye-sensitized solar
      cells (DSSCs). The highest PCE was achieved with complex 10 bearing the sulfonic
      acid anchoring functionality.

PMID- 30222333
TI  - Reversible Hierarchical Assembly of Trimeric Coiled-Coil Peptides into Banded
      Nano- and Microstructures.
AB  - We report a set of coiled-coil peptides, radially functionalized with
      bipyridines, that demonstrate hierarchical assembly into banded rectangular nano-
      and microstructures, the dimensions of which vary with the strategic placement
      and number of aromatic groups on the monomer backbone. Finer structural aspects
      of the hexagonal packing of the individual trimers were determined by X-ray
      scattering, including intertrimer aromatic interactions between bipyridine
      moieties. The ease of formation of these biomaterials under physiological
      conditions and the use of pH to reversibly modulate assembly demonstrate future
      potential for a range of biological applications, such as drug delivery in a pH
      controlled manner.

PMID- 30222332
TI  - Identification of PAmKate as a Red Photoactivatable Fluorescent Protein for
      Cryogenic Super-Resolution Imaging.
AB  - Single-molecule super-resolution fluorescence microscopy conducted in vitrified
      samples at cryogenic temperatures offers enhanced localization precision due to
      reduced photobleaching rates, a chemical-free and rapid fixation method, and the
      potential of correlation with cryogenic electron microscopy. Achieving cryogenic
      super-resolution microscopy requires the ability to control the sparsity of
      emissive labels at cryogenic temperatures. Obtaining this control presents a key
      challenge for the development of this technique. In this work, we identify a red
      photoactivatable protein, PAmKate, which remains activatable at cryogenic
      temperatures. We characterize its activation as a function of temperature and
      find that activation is efficient at cryogenic and room temperatures. We perform
      cryogenic super-resolution experiments in situ, labeling PopZ, a protein known to
      assemble into a microdomain at the poles of the model bacterium Caulobacter
      crescentus. We find improved localization precision at cryogenic temperatures
      compared to room temperature by a factor of 4, attributable to reduced
      photobleaching.

PMID- 30222334
TI  - Remarkable Changes of the Acidity of Bound Nitroxyl (HNO) in the
      [Ru(Me3[9]aneN3)(L2)(NO)] n+ Family ( n = 1-3). Systematic Structural and
      Chemical Exploration and Bioinorganic Chemistry Implications.
AB  - This work demonstrates that the acidity of nitroxyl (HNO) coordinated to a metal
      core is significantly influenced by its coordination environment. The possibility
      that NO- complexes may be the predominant species in physiological environments
      has implications in bioinorganic chemistry and biochemistry. This (apparently
      simple) result pushed us to delve into the basic aspects of HNO coordination
      chemistry. A series of three closely related {RuNO}6,7 complexes have been
      prepared and structurally characterized, namely [Ru(Me3[9]aneN3)(L2)(NO)]3+/2+,
      with L2 = 2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, and 2,2'-bipyrimidine.
      These species have also been thoroughly studied in solution, allowing for a
      systematic exploration of their electrochemical properties in a wide pH range,
      thus granting access and characterization of the elusive {RuNO}8 systems.
      Modulation of the electronic density in the {RuNO} fragment introduced by
      changing the bidentate coligand L2 produced only subtle structural modifications
      but affected dramatically other properties, most noticeably the redox potentials
      of the {RuNO}6,7 couples and the acidity of bound HNO, which spans over a range
      of almost three pH units. Controlling the acidity of coordinated HNO by the
      rational design of coordination compounds is of fundamental relevancy in the
      field of inorganic chemistry and also fuels the growing interest of the community
      in understanding the role that different HNO-derived species can play in
      biological systems.

PMID- 30222335
TI  - In Situ Electrochemical AFM Imaging of a Pt Electrode in Sulfuric Acid under
      Potential Cycling Conditions.
AB  - Understanding the electrochemical behavior of Pt at the solid/liquid interface is
      of significant importance for the development of efficient electrochemical
      devices, such as fuel cells and water electrolyzers. In this work, the evolution
      of the surface morphology of a polycrystalline platinum under potential cycling
      conditions was investigated by in situ electrochemical atomic force microscopy
      (EC-AFM). After 50 cycles between 0.05 and 1.8 V in 0.1 M H2SO4, the Pt surface
      is coarsened and nanoparticles of several nanometers appear on the surface. The
      critical upper and lower potentials for the formation of nanoparticles are found
      to be 1.8 and 0.8 V, respectively. The in situ AFM observation coupled with
      Cyclic Voltammerty reveals the periodic disappearance and reappearance of the
      nanoparticles, based on which the formation of nanoparticles is attributed to the
      deposition of dissolved Pt from solution, and a model for the nanoparticle
      formation is proposed. While the formation of a thick oxide layer is a
      prerequisite, the reduction process is found to have a strong influence on Pt
      nanoparticle formation as well. This investigation provides a visualization of
      the Pt electrode surface under electrochemical control in a large potential
      window, enabling a broader understanding of the Pt electrode roughening
      mechanisms.

PMID- 30222336
TI  - Interfacing Transition Metal Dichalcogenides with Carbon Nanodots for Managing
      Photoinduced Energy and Charge-Transfer Processes.
AB  - Exfoliated semiconducting MoS2 and WS2 were covalently functionalized with 1,2
      dithiolane-modified carbon nanodots (CNDs). The newly synthesized CND-MoS2 and
      CND-WS2 hybrids were characterized by spectroscopic, thermal, and electron
      microscopy imaging methods. Based on electronic absorption and fluorescence
      emission spectroscopy, modulation of the optoelectronic properties of TMDs by
      interfacing with CNDs was accomplished. Electrochemical studies revealed facile
      oxidation of MoS2 over WS2 in the examined hybrids, suggesting it to be better
      electron donor. Excited state events, investigated by femtosecond transient
      absorption spectroscopic studies, revealed ultrafast energy transfer from
      photoexcited CNDs to both MoS2 and WS2. Interestingly, upon MoS2 photoexcitation,
      charge transfer from an exciton dissociation path of MoS2 to CNDs, within CND
      MoS2, was observed. However, such a process in CND-WS2 was found to be absent due
      to energetic reasons. The present study highlights the importance of TMD-derived
      donor-acceptor hybrids in light energy harvesting and optoelectronic
      applications. Furthermore, the fundamental information obtained from the current
      results will benefit design strategies and impact the development of additional
      TMD-based hybrid materials to efficiently manage and perform in electron-transfer
      processes.

PMID- 30222337
TI  - Mercury Isotopic Fractionation during Pedogenesis in a Tropical Forest Soil
      Catena (French Guiana): Deciphering the Impact of Historical Gold Mining.
AB  - We used natural mercury (Hg) stable isotopes to investigate the Hg cycle in a
      rainforest soil catena (French Guiana) partially gold-mined during the early
      1950s. Litterfall showed homogeneous Delta199Hg values [-0.18 +/- 0.050/00, i.e.,
      a modern gaseous elemental Hg (GEM) isotopic signature]. After litter
      decomposition, Hg bound to organic matter (OM) is mixed with Hg from pristine (
      0.55 +/- 0.220/00) or gold-mined (-0.09 +/- 0.160/00) mineral materials. Negative
      Delta199Hg values in deep pristine mineral horizons (-0.60 +/- 0.160/00) suggest
      the transfer of Hg bound to dissolved OM depleted in odd isotopes due to mass
      independent fractionation during Hg abiotic reduction. Perennial palm tree leaves
      collected above gold-mined and pristine soil recorded contrasting Delta199Hg
      signatures likely resulting from GEM re-emission processes from soils and leaf
      surfaces. Upslope, soil delta202Hg signatures showed a negative shift (epsilon ~ 
      10/00) with depth attributed to mass-dependent fractionation during Hg sorption
      and complexation onto iron oxides and dissolved OM. Downslope, higher delta202Hg
      values in soils resulted from hydromorphy [lower humification, greater Hg(II)
      reduction, etc.]. The unique Hg isotopic signatures of Amazonian soils probably
      result in multistep fractionation processes during pedogenesis (millions of
      years) and in a potentially different Hg isotopic signature of preanthropogenic
      background GEM.

PMID- 30222338
TI  - Design of Effective Catalysts for Selective Alkyne Hydrogenation by Doping of
      Ceria with a Single-Atom Promotor.
AB  - Since the discovery that ceria is an active catalyst for selective hydrogenation
      of alkynes, there has been much debate on the catalytic mechanism. In this work,
      we propose, based on density functional theory (DFT) investigations, a mechanism
      that involves the heterolytic dissociation of H2 at oxygen vacancies of
      CeO2(111), facilitated by frustrated Lewis pairs consisting of spatially
      separated O and Ce sites. The resulting O-H and Ce-H species effectively catalyze
      the hydrogenation of acetylene, avoiding the overstabilization of the C2H3*
      intermediate in a previously proposed mechanism. On the basis of our mechanism,
      we propose the doping of ceria by Ni as a means to create oxygen vacancies.
      Interestingly, the Ni dopant is not directly involved in the catalytic reaction,
      but serves as a single-atom promoter. Experimental studies confirm the design
      principles and demonstrate much higher activity for Ni-doped ceria in selective
      hydrogenation of acetylene. The combined results from DFT calculations and
      experiment provide a basis to further develop selective hydrogenation catalysts
      based on earth-abundant materials.

PMID- 30222339
TI  - N-Terminal Domain Truncation and Domain Insertion-Based Engineering of a Novel
      Thermostable Type I Pullulanase from Geobacillus thermocatenulatus.
AB  - A novel thermostable type I pullulanase gene ( pul GT) from Geobacillus
      thermocatenulatus DSMZ730 was cloned. It has an open reading frame of 2154 bp
      encoding 718 amino acids. G. thermocatenulatus pullulanase (PulGT) was found to
      be optimally active at pH 6.5 and 70  degrees C. It exhibited stable activity in
      the pH range of 5.5-7.0. PulGT lacked three domains (CBM41 domain, X25 domain,
      and X45 domain) compared with the pullulanase from Bacillus acidopullulyticus (
      2WAN ). Different N-terminally domain truncated (730T) or spliced (730T-U1 and
      730T-U2) mutants were constructed. Truncating the N-terminal 85 amino acids
      decreased the Km value and did not change its optimum pH, an advantageous
      biochemical property in some applications. Compared with 2WAN , PulGT can be used
      directly for maize starch saccharification without adjusting the pH, which
      reduces cost and improves efficiency.

PMID- 30222341
TI  - Role of Polar and Nonpolar Groups in the Activity of Antifreeze Proteins: A
      Molecular Dynamics Simulation Study.
AB  - Molecular dynamics simulations have been carried out separately with the
      hyperactive Tenebrio molitor antifreeze protein ( TmAFP) and with its nonactive
      mutant at 300 K to elucidate the role of polar and nonpolar groups in the
      activities of antifreeze proteins (AFPs). Simulation results reveal that both
      polar and nonpolar groups contribute to develop the required quasi-ice-like
      hydration layer on the ice-binding surface (IBS) of an AFP for binding onto ice.
      Nonpolar groups on the IBS induce the formation of locally ordered icelike low
      density waters in the hydration layer through hydrophobic interactions, and polar
      groups of the surface integrate these waters into a quasi-ice-like layered
      structure through hydrogen-bonding interactions. These contributions of polar and
      nonpolar groups apparently contradict the behavior of winter flounder antifreeze
      protein (wfAFP) mutants possibly due to switching of IBS of wfAFP upon mutation
      of threonine residues with valine residues.

PMID- 30222340
TI  - Protein Conformational Transitions from All-Atom Adaptively Biased Path
      Optimization.
AB  - Simulation methods are valuable for elucidating protein conformational
      transitions between functionally diverse states given that transition pathways
      are difficult to capture experimentally. Nonetheless, specific computational
      algorithms are required because of the high free energy barriers between these
      different protein conformational states. Adaptively biased path optimization
      (ABPO) is an unrestrained, transition-path optimization method that works in a
      reduced-variable space to construct an adaptive biasing potential to aid
      convergence. ABPO was previously applied using a coarse-grained Go-model to study
      conformational activation of Lyn, a Src family tyrosine kinase. How effectively
      ABPO can be applied at the higher resolution of an all-atom model to explore
      protein conformational transitions is not yet known. Here, we report the all-atom
      conformational transition paths of three protein systems constructed using the
      ABPO methodology. Two systems, triose phosphate isomerase and dihydrofolate
      reductase, undergo local flipping of a short loop that promotes ligand binding.
      The third system, estrogen receptor alpha ligand binding domain, has a helix that
      adopts different conformations when the protein is bound to an agonist or an
      antagonist. For each protein, distance-based or torsion-angle reduced variables
      were identified from unbiased trajectories. ABPO was computed in this reduced
      variable space to obtain the transition path between the two states. The all-atom
      ABPO is shown to successfully converge an optimal transition path for each of the
      three systems.

PMID- 30222342
TI  - Formation Constants and Conformational Analysis of Carbamates in Aqueous
      Solutions of 2-Methylpiperidine and CO2 from 283 to 313 K by NMR Spectroscopy.
AB  - Quantitative 13C nuclear magnetic resonance (NMR) spectroscopy was used to
      investigate the speciation in (2-methylpiperidine + H2O + CO2) systems at 283.2
      313.2 K. The carbamate of 2-methylpiperidine(2-methylpiperidine- N-carboxylate)
      was shown for the first time to be a stable species in aqueous solutions. The
      spectroscopic results were used to obtain temperature-dependant formation
      constants for the carbamate using a simplified model for the activity
      coefficients from which the standard molar enthalpy of reaction was estimated.
      The results were incorporated into a self-consistent chemical equilibrium model,
      which includes vapor-liquid equilibria and all aqueous species, including the
      formation of carbamate. The predominant conformation of the sterically hindered
      carbamate, which was determined using two-dimensional exchange spectroscopy NMR,
      has the methyl group in the axial orientation and is in agreement with the
      density functional theory quantum chemical calculations.

PMID- 30222343
TI  - Dinghupeptins A-D, Chymotrypsin Inhibitory Cyclodepsipeptides Produced by a Soil
      Derived Streptomyces.
AB  - Four new cyclodepsipeptides, dinghupeptins A-D (1-4), possessing a rare N5-(2
      hydroxylethyl)glutamine moiety, were isolated from cultures of the soil-derived
      Streptomyces sp. SC0581. Their structures were elucidated by spectroscopic and
      advanced Marfey's amino acid analysis, and their 3D structures were established
      by theoretical conformational analysis. Compounds 1 and 2, containing a 3-amino-6
      hydroxypiperidone unit, displayed selective inhibition of chymotrypsin with IC50
      values of 2.1 and 1.1 MUM, respectively. Enzyme kinetic analysis and molecular
      docking experiments revealed they are competitive inhibitors binding to the
      active site of chymotrypsin.

PMID- 30222344
TI  - Extraction Properties of New Polymeric Sorbents Applied to Wine.
AB  - Polymeric sorbents are frequently used in wine, either as solid phase extraction
      materials for isolation of analytes or as sorptive materials for removal of
      undesirable compounds (amelioration). Six new polymeric sorbents were produced
      thermally or in a microwave from various ratios of methacrylic acid, acrylic
      acid, and 4-vinylbenzoic acid as hydrophilic monomers, together with ethylene
      glycol dimethacrylate as cross-linker, using different porogen solvents. The
      relationship between physicochemical properties (pore size, surface area, and
      polarity) of the sorbents and their sorption properties for compounds in wine was
      investigated and compared to four commercially available sorbents. With some
      similarities to their commercial counterparts depending on hydrophobic and
      hydrophilic characteristics, the six new sorbents showed specificity toward
      different groups of compounds (e.g., volatiles and phenolics) and could be
      applied for targeted purposes. The results provide insight into the selection and
      utilization of new polymeric materials for extraction of components from wine.

PMID- 30222345
TI  - Ab Initio Simulation of pH-Sensitive Biomarkers in Magnetic Resonance Imaging.
AB  - An ab initio simulation scheme is introduced as a theoretical prescreening
      approach to facilitate and enhance the research for pH-sensitive biomarkers. The
      proton 1H and carbon 13C nuclear magnetic resonance (NMR) chemical shifts of the
      recently published marker for extracellular pH, [1,5-13C2]zymonic acid (ZA), and
      the as yet unpublished ( Z)-4-methyl-2-oxopent-3-enedioic acid (OMPD) were
      calculated with ab initio methods as a function of the pH. The influence of the
      aqueous solvent was taken into account either by an implicit solvent model or by
      explicit water molecules, where the latter improved the accuracy of the
      calculated chemical shifts considerably. The theoretically predicted chemical
      shifts allowed for a reliable NMR peak assignment. The p Ka value of the first
      deprotonation of ZA and OMPD was simulated successfully whereas the
      parametrization of the implicit solvent model does not allow for an accurate
      description of the second p Ka. The theoretical models reproduce the pH-induced
      chemical shift changes and the first p Ka with sufficient accuracy to establish
      the ab initio prescreening approach as a valuable support to guide the
      experimental search for pH-sensitive biomarkers.

PMID- 30222346
TI  - Short-Term Nitrate Limitation Prior to Harvest Improves Phenolic Compound
      Accumulation in Hydroponic-Cultivated Lettuce ( Lactuca sativa L.) without
      Reducing Shoot Fresh Weight.
AB  - Long-term exposure to a low nitrogen supply could effectively improve phenolic
      content in vegetables, but it also greatly decreases the yield. Therefore, it is
      necessary to develop cost-effective strategies of nitrogen management to overcome
      these obstacles. Here, we find that decreasing the nitrogen (NO3-) supply from
      8.0 to below 2.0 mM during the last 7 days before harvest significantly increases
      phenolic levels and antioxidant capacity of the soluble fraction in two
      hydroponic-cultivated lettuces, which is demonstrated by the up-regulation of
      related genes ( PAL1, CHS, F3H, DFR, F35H, and UFGT) involved in the phenolic
      synthesis pathway. Importantly, short-term nitrate limitation before harvest does
      not affect yield production unless nitrogen supply is reduced below 1.0 and 0.5
      mM for Ziluoma and Lvluo, respectively. These findings suggest that appropriate
      short-term nitrate limitation before harvest, considering genotype variation, is
      feasible for improving the phenolic content and antioxidant capacity of
      vegetables without reducing their yield.

PMID- 30222347
TI  - Binding Interaction of Organofluorine-Serum Albumin: A Comparative Ligand
      Detected 19F NMR Analysis.
AB  - In the present study, we attempt to characterize fluorinated ligand-serum albumin
      interaction in solution by a set of one-dimensional 19F ligand-based experiments.
      In this regard, a model system diflunisal (DFL)-human serum albumin (HSA) has
      been chosen to benchmark the utility of 19F relaxation and diffusion-based
      experiments in deciphering ligand-protein interactions. Further, we extend the
      application of a similar set of 19F experiments to unravel the molecular
      interaction in an unexplored system of 2,6-difluorobenzoic acid (DFBA)-bovine
      serum albumin (BSA). Interaction analysis of DFBA-SA is of particular interest
      because DFBA is not only a stable metabolite of a number of pesticides but also
      used as the starting reagent of many fluorinated drugs. Observation of 19F-1H &
      1H-1H saturation transfer difference effects confirmed binding of the ligands to
      SA. Further, these ligand-protein complexes were probed in terms of the
      dissociation constant ( KD), number of binding sites ( n), bound fraction of the
      ligand ( Pb), the complex lifetime (taures), and exchange rate ( Kex). Although
      Carr-Purcell-Meiboom-Gill (CPMG)-based transverse relaxation and diffusion
      analysis quantified the former three quantities, the latter two were determined
      by the constant time fast pulsing CPMG method. Additionally, 19F competition
      binding experiments performed with well-characterized BSA site markers and DFBA
      indicated nonspecific binding of DFBA to BSA, whereas similar measurements in the
      case of HSA with DFL and DFBA revealed superior binding interaction of DFL with
      SA.

PMID- 30222348
TI  - Interpreting Hydrogen-Deuterium Exchange Events in Proteins Using Atomistic
      Simulations: Case Studies on Regulators of G-Protein Signaling Proteins.
AB  - Hydrogen-deuterium exchange (HDX) experiments are widely used in studies of
      protein dynamics. To predict the propensity of amide hydrogens for exchange with
      deuterium, several models have been reported in which computations of amide
      hydrogen protection factors are carried out using molecular dynamics (MD)
      simulations. Given significant variation in the criteria used in different
      models, the robustness and broader applicability of these models to other
      proteins, especially homologous proteins showing distinct amide-exchange
      patterns, remains unknown. The sensitivity of the predictions when MD simulations
      are conducted with different force-fields is yet to tested and quantified. Using
      MD simulations and experimental HDX data on three homologous signaling proteins,
      we report detailed studies quantifying the performance of seven previously
      reported models (M1-M7) of two general types: empirical and fractional-population
      models. We find that the empirical models show inconsistent predictions but
      predictions of the fractional population models are robust. Contrary to
      previously reported work, we find that the solvent-accessible surface area of
      amide hydrogens is a useful metric when combined with a new metric defining the
      distances of amide hydrogens from the first polar atoms in proteins. On the basis
      of this, we report two new models, one empirical (M8) and one population-based
      (M9). We find strong protection of amide hydrogens from solvent exchange both
      within the stable helical motifs and also in the interhelical loops. We further
      observe that the exchange-competent states of amide hydrogens occur on the sub
      100 ps time-scale via localized fluctuations, and such states among amides of a
      given protein do not appear to show any cooperativity or allosteric coupling.

PMID- 30222349
TI  - Structure of Strontium Aluminosilicate Glasses from Molecular Dynamics
      Simulation, Neutron Diffraction, and Nuclear Magnetic Resonance Studies.
AB  - The structure of strontium glasses with the composition (SiO2)1-2 x(Al2O3) x(SrO)
      x ( R = [SrO]/[Al2O3] = 1) and (SiO2)1-4 x(Al2O3) x(SrO)3 x ( R = 3) has been
      explored experimentally over both short- and intermediate-length scales using
      neutron diffraction, 27Al and 29Si nuclear magnetic resonance, and classical
      molecular dynamics simulations in model systems containing around 10 000 atoms.
      We aim at understanding the structural role of aluminum and strontium as a
      function of the chemical composition of these glasses. The short- and medium
      range structure such as aluminum coordination, bond angle distribution, Q( n)
      distribution, and oxygen speciation have been systematically studied. Two
      potential forms of the repulsive short-range interactions have been investigated,
      namely, the Buckingham and Morse forms. The comparison of these forms allows us
      to derive general trends independent of the particular choice of the potential
      form. In both cases, it is found that aluminum ions are mainly fourfold
      coordinated and mix with the silicon network favoring the Al/Si mixing in terms
      of Al-O-Si linkages. For the R = 1 glass series, despite the full charge
      compensation ([SrO] = [Al2O3]), a small fraction of fivefold aluminum is observed
      both experimentally and in MD simulations, whereas the concentration of sixfold
      aluminum is negligible. MD shows that the fivefold aluminum units AlO5
      preferentially adopt a small ring configuration and link to tricoordinated oxygen
      atoms whose population increases with the aluminum content and are mainly found
      in OAl3 and OAl2Si configurations. The modeled Sr speciation mainly involves SrO7
      and SrO8 polyhedra, giving a range of average Sr2+ coordination numbers between 7
      and 8 slightly dependent on the short-range repulsive potential form. A detailed
      statistical analysis of T-O-T' (T, T' = Al,Si), accounting for the population of
      the various oxygen speciations, reveals that both potentials predict a nearly
      identical Al/Si mixing.

PMID- 30222350
TI  - Metadynamics with Discriminants: A Tool for Understanding Chemistry.
AB  - We introduce an extension of a recently published method [ Mendels et al. J.
      Phys. Chem. Lett. 2018 , 9 , 2776 - 2781 ] to obtain low-dimensional collective
      variables for studying multiple states free energy processes in chemical
      reactions. The only information needed is a collection of simple statistics of
      the equilibrium properties of the reactants and product states. No information on
      the reaction mechanism has to be given. The method allows studying a large
      variety of chemical reactivity problems including multiple reaction pathways,
      isomerization, and stereo- and regiospecificity. We applied the method to two
      fundamental organic chemical reactions. First we study the SN2 nucleophilic
      substitution reaction of a Cl in CH2Cl2 leading to an understanding of the
      kinetic origin of the chirality inversion in such processes. Subsequently, we
      tackle the problem of regioselectivity in the hydrobromination of propene
      revealing that the nature of empirical observations such as Markovnikov's rule
      lies in the chemical kinetics rather than the thermodynamic stability of the
      products.

PMID- 30222351
TI  - Species Differentiation and Quantification of Processed Animal Proteins and Blood
      Products in Fish Feed Using an 8-Plex Mass Spectrometry-Based Immunoassay.
AB  - With the reintroduction of nonruminant processed animal proteins (PAPs) for use
      in aquaculture in 2013, there is a suitable alternative to replace expensive fish
      meal in fish feed. Nevertheless, since the bovine spongiform encephalopathy (BSE)
      crisis, the use of PAPs in feed is strictly regulated. To date, light microscopy
      and polymerase chain reaction are the official methods for proving the absence of
      illegal PAPs in feed. Due to their limitations, alternative methods for the
      quantitative species differentiation are needed. To address this issue, we
      developed and validated an 8-plex mass spectrometry-based immunoassay. The
      workflow comprises a tryptic digestion of PAPs and blood products in suspension,
      a cross-species immunoaffinity enrichment of 8 species-specific alpha-2
      macroglobulin peptides using a group-specific antibody, and a subsequent analysis
      by ultrahigh-performance liquid chromatography coupled to tandem mass
      spectrometry for species identification and quantification. This workflow can be
      used to quantitatively determine the species origin in future feed authentication
      studies.

PMID- 30222352
TI  - Dynamic Kinetic Resolution for Construction of Three Transannular Stereocenters
      of Dihydrobenzofuranols.
AB  - A handy and effective method was established to obtain the cis-2,3
      dihydrobenzofuranols having three stereocenters, involving asymmetric transfer
      hydrogenation of benzofuranones via dynamic kinetic resolution. The general
      applicability of this method was examined with different benzofuran-3-(2 H)-ones,
      and stereoselectivities of 85-99% ee and up to 98/2 dr were obtained.

PMID- 30222353
TI  - Ion Gel Network Formation in an Ionic Liquid Studied by Time-Resolved Small-Angle
      Neutron Scattering.
AB  - We report the time-resolved small-angle neutron scattering (SANS) study of tetra
      arm poly(ethylene glycol) (TetraPEG) polymer network formation in a typical ionic
      liquid (IL), 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide
      ([C2mim][TFSA]). To observe time-dependent SANS profiles, the reaction rate for
      the AB-type cross-end coupling reaction of TetraPEG macromers was controlled by
      adding an analogous protic IL, 1-ethylimidazolium TFSA ([C2imH][TFSA]). At
      polymer concentrations higher than the overlap concentration ( c*), the SANS
      profile remained unchanged during the gelation reaction, indicating that the
      network structure was independent of macromer connectivity in a semidiluted
      solution. On the other hand, at low polymer concentrations, an increase in the
      SANS profile intensity was clearly observed. The correlation length (xi),
      estimated by a fitting analysis based on the Ornstein-Zernike function, increased
      as the reaction proceeded. This result indicated that the sparsely dispersed
      macromers formed clusters during the cross-linking process and polymer size
      growth followed thereafter. We found that the network formation process and
      homogeneity of the network structure were strongly dependent on the polymer
      concentration in IL solutions.

PMID- 30222355
TI  - Water, Ions, and Hemoglobin: Effects on Allostery and Polymerization.
AB  - Proteins that function in aqueous solution can be perturbed by the solvent. Here
      we present experimental studies on two such interactions in the hemoglobin
      molecule. (1) Hemoglobin's oxygen binding is altered by introduction of crowding
      species or osmoticants, such as sucrose, through the linked binding of ions such
      as Cl or CO2, but not otherwise. This rules out a significant role of buried
      surface in the allosteric energetics. (2) Sickle hemoglobin (HbS) polymerizes
      more readily in high concentrations of phosphate buffer. Such polymerization is
      analyzed quantitatively here for the first time in terms of the double nucleation
      mechanism. The changes in solubility are found to account for the increase in
      monomer addition rates and nucleation rates without requiring additional
      parameter adjustments. In the analysis, we also show how the analytical
      formulation of HbS nucleation may be adapted to include water that occupies the
      interstices between the assembled molecules. While such a "correction" has been
      applied to the equilibrium process, it has not previously been applied to the
      nucleation process.

PMID- 30222356
TI  - Effects of Protein Corona on Active and Passive Targeting of Cyclic RGD Peptide
      Functionalized PEGylation Nanoparticles.
AB  - Protein corona can alter the physiochemical properties of targeting nanoparticles
      (NPs), as well as their physiological responses and targeting functionality.
      Herein, we synthesized 20 types of NPs with diverse surface chemistry in order to
      study the impacts of protein corona on targeting functionality of NPs
      functionalized with cyclic RGD peptides and their relationships to the
      polyethylene glycol (PEG) length and grafting density of targeting ligands. After
      protein adsorption, cyclic RGD on the surface of NP was still able to bind its
      receptors with increased targeted cellular uptake, even at a relatively low
      density. However, the cellular uptake was reduced from 26 to 76% when compared
      with protein nonbound NPs, which was caused by the shielding effect of the outer
      layer adsorbed proteins. NPs functionalized with short PEG molecules and moderate
      cyclic RGD density performed a better targeting efficiency. Due to PEG
      conjugation, the protein corona was demonstrated to be beneficial for passive
      targeting by decreasing macrophage cellular uptake. These relationships between
      surface chemistry and targeting functionality will provide guidelines for the
      design of targeting nanoformulations in nanomedicine.

PMID- 30222354
TI  - Site-Specific Incorporation of a Cu2+ Spin Label into Proteins for Measuring
      Distances by Pulsed Dipolar Electron Spin Resonance Spectroscopy.
AB  - Pulsed dipolar electron spin resonance spectroscopy (PDS) is a powerful tool for
      measuring distances in solution-state macromolecules. Paramagnetic metal ions,
      such as Cu2+, are used as spin probes because they can report on metalloprotein
      features and can be spectroscopically distinguished from traditional nitroxide
      (NO)-based labels. Here, we demonstrate site-specific incorporation of Cu2+ into
      non-metalloproteins through the use of a genetically encodable non-natural amino
      acid, 3-pyrazolyltyrosine (PyTyr). We first incorporate PyTyr in cyan fluorescent
      protein to measure Cu2+-to-NO distances and examine the effects of solvent
      conditions on Cu2+ binding and protein aggregation. We then apply the method to
      characterize the complex formed by the histidine kinase CheA and its target
      response regulator CheY. The X-ray structure of CheY-PyTyr confirms Cu labeling
      at PyTyr but also reveals a secondary Cu site. Cu2+-to-NO and Cu2+-to-Cu2+ PDS
      measurements of CheY-PyTyr with nitroxide-labeled CheA provide new insights into
      the conformational landscape of the phosphotransfer complex and have implications
      for kinase regulation.

PMID- 30222357
TI  - Proteome-Wide Structural Biology: An Emerging Field for the Structural Analysis
      of Proteins on the Proteomic Scale.
AB  - Over the past decade, a suite of new mass-spectrometry-based proteomics methods
      has been developed that now enables the conformational properties of proteins and
      protein-ligand complexes to be studied in complex biological mixtures, from cell
      lysates to intact cells. Highlighted here are seven of the techniques in this new
      toolbox. These techniques include chemical cross-linking (XL-MS), hydroxyl
      radical footprinting (HRF), Drug Affinity Responsive Target Stability (DARTS),
      Limited Proteolysis (LiP), Pulse Proteolysis (PP), Stability of Proteins from
      Rates of Oxidation (SPROX), and Thermal Proteome Profiling (TPP). The above
      techniques all rely on conventional bottom-up proteomics strategies for peptide
      sequencing and protein identification. However, they have required the
      development of unconventional proteomic data analysis strategies. Discussed here
      are the current technical challenges associated with these different data
      analysis strategies as well as the relative analytical capabilities of the
      different techniques. The new biophysical capabilities that the above techniques
      bring to bear on proteomic research are also highlighted in the context of
      several different application areas in which these techniques have been used,
      including the study of protein ligand binding interactions (e.g., protein target
      discovery studies and protein interaction network analyses) and the
      characterization of biological states.

PMID- 30222358
TI  - Two-Channel Thermal Transport in Ordered-Disordered Superionic Ag2Te and Its
      Traditionally Contradictory Enhancement by Nanotwin Boundary.
AB  - A recent experiment [ J. Mater. Chem. A 2015 , 3 , 10303 ] has proved that
      superionic Ag2Te can achieve a figure of merit as high as 1.39 due to its
      extremely low thermal conductivity. However, the traditional lattice vibration
      concept, i.e., phonons regarded as heat carriers, fails to explain the governing
      mechanism in such structures where anions vibrate around their equilibrium
      positions while cations flow like a liquid. As a result, the underlying physics
      for thermal transport properties in superionic Ag2Te is still a mystery. In this
      study, two-channel heat transport in such ordered-disordered systems (i.e.,
      lattice vibrations and liquid-like mobile ions coexist) is quantitatively
      characterized on the basis of the heat flux linear response theory. Our results
      show that the convective thermal conductivity is dominant in the system, which
      results from the free movement of Ag ions. As a consequence, the total thermal
      conductivity increases abnormally with temperature due to the strengthened
      cations' mobilities at elevated temperatures. Meanwhile, the effect of
      experimentally observed nanotwin boundaries [ Acta Mater. 2017 , 128 , 43 ],
      which facilitate electrical transport in crystals, on heat carriers are also
      investigated. In contradiction to the classical heat transport theory, in which
      heat carriers are hindered by boundaries, the nanotwin boundary in superionic
      Ag2Te unexpectedly improves thermal transport due to the enhanced movement of Ag
      ions around the grain boundary. This exhaustive explanation of thermal transport
      properties in superionic Ag2Te will support the future design of superionic
      conductors based on thermoelectrics and more broad energy systems composed of
      ordered-disordered materials.

PMID- 30222360
TI  - Improved Cancer Immunochemotherapy via Optimal Co-delivery of Chemotherapeutic
      and Immunomodulatory Agents.
AB  - It is highly demanded and still a big challenge to develop an effective
      formulation for immunochemotherapy against advanced tumors. We have previously
      reported a PEG-NLG-based immunostimulatory nanocarrier (PEG2k-Fmoc-NLG919) for co
      delivery of an IDO1 inhibitor (NLG919) and a chemotherapeutic agent (paclitaxel,
      PTX). Although antitumor immune responses were enhanced with a PTX-loaded
      nanocarrier, the accumulation of myeloid-derived suppressor cells (MDSCs) was
      also significantly increased, which may limit the overall efficacy of therapy. In
      the present work, we developed an improved dual-functional nanocarrier (PEG5k
      Fmoc-NLG2) to co-load PTX and sunitinib (SUN, a multitarget receptor tyrosine
      kinase inhibitor) for improved cancer immunochemotherapy. We found that the
      recruited MDSCs negatively impacted the overall antitumor activity of the PTX
      loaded PEG-NLG nanocarrier. Mechanistic study suggests that this is likely
      attributed to the PTX-mediated induction of a number of chemokines that are
      involved in the recruitment of MDSCs. We have further shown that the induction of
      these chemokines was drastically blocked by SUN. Co-delivery of PTX and SUN via
      the PEG5k-Fmoc-NLG9192 nanocarrier led to a further improvement in the
      therapeutic efficacy with a concomitant reduction in MDSCs.

PMID- 30222359
TI  - Synergistic Targeting HER2 and EGFR with Bivalent Aptamer-siRNA Chimera
      Efficiently Inhibits HER2-Positive Tumor Growth.
AB  - HER2 overexpression is identified on 20-30% breast cancer and other cancers at
      different levels. Although HER2 targeted monoclonal antibody combined with
      chemical drugs has shown improved outcomes in HER2 expressing patients, drug
      resistance and toxicity have limited their efficacy. To overcome drug resistance,
      cotargeting  multiple HER receptors was proven to be effective. EGFR/HER2
      dimerization can active PI3K/AKT pathway, and resistance to HER2-targeted drugs
      is associated with upregulation of EGFR. Here, we developed a novel HER2/EGFR
      targeted nucleic acid therapeutic to address current drug limits. The new
      therapeutic is constructed by fusing HER2 aptamer-EGFR siRNA sense strand with
      HER2 aptamer-EGFR siRNA antisense strand into one molecule: a bivalent HER2
      aptamer-EGFR siRNA aptamer chimera (HEH). In breast cancer cell lines, HEH can be
      selectively taken up into HER2 expressing cells and successfully silence EGFR
      gene and down regulate HER2 expression. In breast cancer xenograft models, HEH is
      capable of triggering cell apoptosis, decreasing HER2 and EGFR expression, and
      suppressing tumor growth. The therapeutic efficacy of HEH is superior to HER2
      aptamer only, which suggests that HEH has synergistic effect by targeting HER2
      and EGFR. This study demonstrated that HEH has great potential as a new HER2
      targeted drug to address toxicity and resistance of current drugs and may provide
      a cure for many HER2 positive cancers.

PMID- 30222361
TI  - Atypical Defect Motions in Brittle Layered Sodium Titanate Nanowires.
AB  - In situ tensile tests show atypical defect motions in the brittle Na2Ti3O7 (NTO)
      nanowire (NW) within the elastic deformation range. After brittle fracture,
      elastic recovery of the NTO NW is followed by reversible motion of the defects in
      a time-dependent manner. An in situ cyclic loading-unloading test shows that
      these mobile defects shift back and forth along the NW in accordance with the
      loading-unloading cycles and eventually restore their initial positions after the
      load is completely removed. The existence of the defects within the NTO NWs and
      their motions does not lead to plastic deformation of the NW. The atypical defect
      motion is speculated to be the result of the glidibility of the TiO6 layers,
      where weakly bonded cation layers are in between. Exploration of the above novel
      observation can establish new understandings of the deformation behavior of
      superlattice nanostructures.

PMID- 30222362
TI  - Evaluating the Utility of Canine Mdr1 Knockout Madin-Darby Canine Kidney I Cells
      in Permeability Screening and Efflux Substrate Determination.
AB  - Permeability assays are commonly conducted with Madin-Darby canine kidney (MDCK)
      cells to predict the intestinal absorption of small-molecule drug candidates. In
      addition, MDCK cells transfected to overexpress efflux transporters are often
      used to identify substrates. However, MDCK cells exhibit endogenous efflux
      activity for a significant proportion of experimental compounds, potentially
      leading to the underestimation of permeability and confounded findings in
      transport studies. The goal of this study was to evaluate canine Mdr1 knockout
      MDCK (gMDCKI) cells in permeability screening and human MDR1 substrate
      determination in a drug discovery setting. The gMDCKI cells were established by
      CRISPR-Cas9-mediated knockout of the canine Mdr1 gene in MDCKI wildtype (wt)
      cells. A comparison of efflux ratios (ER) between MDCKI wt and gMDCKI showed that
      out of 135 compounds tested, 38% showed efflux activity in MDCKI wt, while no
      significant efflux was observed in gMDCKI cells. Apparent permeability (Papp)
      from apical-to-basolateral (A-to-B) and basolateral-to-apical were near unity in
      gMDCKI cells, which approximated passive permeability, and 17% of compounds
      demonstrated increases in their Papp A-to-B values. Overexpression of human MDR1
      in gMDCKI (gMDCKI-MDR1) cells enabled substrate determination without the
      contribution of endogenous efflux, and the assay was able to deconvolute
      ambiguous results from MDCKI-MDR1 and identify species differences in substrate
      specificity. An analysis of 395 and 474 compounds in gMDCKI and gMDCKI-MDR1,
      respectively, suggested physicochemical properties that were associated with low
      permeability correlated with MDR1 recognition. Poorly permeable compounds and
      MDR1 substrates were more likely to be large, flexible, and more capable of
      forming external hydrogen bonds. On the basis of our evaluation, we concluded
      that gMDCKI is a better cell line for permeability screening and efflux substrate
      determination than the MDCK wt cell line.

PMID- 30222363
TI  - Optical Fluid Pump: Generation of Directional Flow via Microphase
      Segregation/Homogenization.
AB  - We report the successful generation of directional liquid-flow under stationary
      laser irradiation at a fixed position in a chamber. We adopt a homogeneous
      solution consisting of a mixture of water and triethylamine (TEA), with a
      composition near the critical point for phase segregation. When geometrical
      asymmetry is introduced around the laser focus in the chamber, continuous
      directional flow is generated, accompanied by the emergence of water-rich
      microdroplets at the laser focus. The emerging microdroplets tend to escape
      toward the surrounding bulk solution and then merge/annihilate into the
      homogeneous solution. The essential features of the directional flow are
      reproduced through a simple numerical simulation using fluid dynamic equations.

PMID- 30222364
TI  - Prospective Safety Evaluation of a Cardiovascular Health Dietary Supplement in
      Adults with Prehypertension and Stage I Hypertension.
AB  - OBJECTIVE: To prospectively examine the long-term safety of a cardiovascular
      health dietary supplement by assessing a comprehensive set of safety measures.
      DESIGN: Single-arm, open-label study. LOCATION: National University of Natural
      Medicine, Portland, OR. SUBJECTS: Thirty adults with screening blood pressure
      readings consistent with prehypertension or stage I hypertension. INTERVENTION:
      One caplet per day of a dietary supplement for 6 months. The investigated herbal
      mineral supplement contains several ingredients, most notably Rauwolfia
      serpentina. OUTCOME MEASURES: Primary measures included b-type natriuretic
      peptide (NT-proBNP), aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), estimated glomerular filtration rate (eGFR), electrolytes, and the Patient
      Health Questionnaire (PHQ-9). Exploratory measures included physical vital signs,
      cholesterol levels, high-sensitivity cardiac troponin-I, cystatin C, endothelin,
      interleukin (IL)-6, IL-17a, tumor necrosis factor-alpha, high-sensitivity C
      reactive protein, blood counts, and the Patient Reported Outcome Measure
      Information System (PROMIS) Sleep Disturbance Short Form 8b. RESULTS: NT-proBNP,
      AST, ALT, eGFR, sodium, calcium, magnesium, PHQ-9 score, and the majority of
      exploratory measures did not change. However, serum potassium increased (p <
      0.05), systolic blood pressure decreased (p < 0.0001), and diastolic blood
      pressure decreased (p < 0.0001). There were no serious adverse events, but 30% of
      participants withdrew citing potential side effects, most commonly nasal
      congestion or fatigue; most participants who reported nasal congestion also
      reported concomitant seasonal allergies. Adherence to the supplement was 90.9%.
      CONCLUSIONS: The findings of this study suggest that the investigated dietary
      supplement is safe for long-term use in adults with prehypertension and stage I
      hypertension. Additional results of this study, particularly the increase in
      serum potassium and decreases in systolic and diastolic blood pressure, are
      promising and suggest that future research on this dietary supplement, or its
      ingredients, should further explore effects on blood pressure and biologic
      mechanisms of action, which may involve potassium-sparing and diuretic effects.

PMID- 30222365
TI  - Expression Analysis of PVT1, CCDC26, and CCAT1 Long Noncoding RNAs in Acute
      Myeloid Leukemia Patients.
AB  - BACKGROUND: Recent evidence indicates that the PVT1, CCDC26, and CCAT1 long
      noncoding RNAs (lncRNAs) are involved in the leukemogenic process. This study
      quantified the expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs in
      patients with acute myeloid leukemia (AML) and also correlated their expression
      levels with the clinicopathological features of the patients. MATERIALS AND
      METHODS: The expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs were
      analyzed using quantitative reverse transcription-polymerase chain reaction of
      bone marrow specimens obtained from 86 AML patients, 48 AML-M3 patients, and 40
      normal controls. RESULTS: No differences were found between the combined AML
      patient populations and the healthy controls with respect to the expression
      levels of PVT1, CCDC26, and CCAT1 (p = 0.35, p = 0.09, and p = 0.77,
      respectively). However, compared with the controls, the AML-M3 patients had
      higher PVT1 expression (p = 0.017). Furthermore, high-risk AML-M3 patients
      manifested higher expression levels of PVT1 than low- and intermediate-risk
      groups. In addition, distinctive CCDC26 and CCAT1 expression levels were observed
      among patients with different French-American-British subtypes (p = 0.001 for
      CCDC26 and p = 0.013 for CCAT1). Compared with the healthy controls, AML-M4 and
      M5 had higher CCAT1 expression (p = 0.04) and AML-M2 and AML-M4/M5 patients had
      higher CCDC26 expression (p < 0.001 and p = 0.02, respectively). In addition,
      different patterns of CCDC26 expression were found among the different
      cytogenetic risk subtypes (p = 0.005). Finally, patients with intermediate
      cytogenetic risk showed higher CCDC26 expression levels. CONCLUSION: The
      differential expression of the PVT1, CCDC26, and CCAT1 lncRNAs in different AML
      subtypes suggests that the deregulation of these transcripts may function in the
      multistep leukemogenic process and that they may serve as new therapeutic targets
      for this malignancy.

PMID- 30222366
TI  - Roles of Prion Protein in Virus Infections.
AB  - The normal cellular prion protein, designated PrPC, is a membrane glycoprotein
      expressed most abundantly in brains, particularly by neurons, and to a lesser
      extent in non-neuronal tissues including lungs. Conformational conversion of PrPC
      into the amyloidogenic isoform is a key pathogenic event in prion diseases. We
      recently found that PrPC has a protective role against infection with influenza A
      viruses (IAVs) in mice by reducing reactive oxygen species in the lungs after
      infection with IAVs. The antioxidative activity of PrPC is probably attributable
      to its function to activate antioxidative enzyme Cu/Zn-superoxide dismutase, or
      SOD1, through regulating Cu content in lungs infected with IAVs. Oxidative stress
      could play a pivotal role in the pathogenesis of a wide range of viral
      infections. Here, we introduce our and others' studies on the role of PrPC in
      viral infections, and raise the attractive possibility that PrPC might be a novel
      target molecule for development of antioxidative therapeutics against not only
      IAV infection but also other viral infections.

PMID- 30222367
TI  - Effects of Dapagliflozin on 24-Hour Glycemic Control in Patients with Type 2
      Diabetes: A Randomized Controlled Trial.
AB  - BACKGROUND: Glycated hemoglobin (HbA1c) and measures of short-term glycemia do
      not fully capture daily patterns in plasma glucose dynamics. This study evaluated
      24-h glycemic profiles in patients with type 2 diabetes (T2D) initiated on
      dapagliflozin treatment using continuous glucose monitoring (CGM). METHODS: This
      randomized double-blind placebo-controlled multicenter parallel-design 4-week
      study compared dapagliflozin (10 mg/d; n = 50) with placebo (n = 50) in adult
      patients with T2D uncontrolled (HbA1c 7.5%-10.5%) on either stable doses of
      metformin monotherapy (>=1500 mg/d) or insulin (>=30 U/d with or without up to
      two oral antidiabetes drugs). CGM was used to measure 24-h glycemic profiles for
      7 days pretreatment and during week 4 of treatment. The primary outcome was
      change from baseline in 24-h mean glucose (MG) at week 4. RESULTS: The 24-h MG
      decreased 18.2 mg/dL with dapagliflozin and increased 5.8 mg/dL with placebo (P <
      0.001). The proportion of time spent in the target glucose range (70-180 mg/dL)
      increased significantly with dapagliflozin versus placebo (69.6% vs. 52.9%; P <
      0.001), with a small (0.3%) increase in time spent in the hypoglycemic range (<70
      mg/dL), driven by those on background insulin therapy. Dapagliflozin reduced
      postprandial glucose and significantly decreased overall glucose variability. Few
      events of symptomatic hypoglycemia occurred. The most common adverse event was
      urinary tract infection (6% in each treatment arm). CONCLUSIONS: Compared with
      placebo, dapagliflozin improved measures of glycemic control and variability as
      assessed by CGM. Glycemic improvements were more pronounced in the group on
      background metformin than those receiving basal insulin.

PMID- 30222368
TI  - A service evaluation of parent adherence with dysphagia management therapy
      guidelines: reports from family carers supporting children with complex needs in
      Greece.
AB  - PURPOSE: Many children with complex needs exhibit eating, drinking, and/or
      swallowing disorders (dysphagia). These children often have associated learning
      needs, and require assistance from carers for daily tasks such as eating and
      drinking. The aim of this study was to identify which strategies to manage
      dysphagia were challenging for family carers, and reasons for any non-adherence.
      METHOD: In this service evaluation researchers observed carers during mealtimes,
      and investigated carer opinions of strategies used to minimise the risks of
      dysphagia. Eight children with complex needs aged 3.4-7.5 years and their primary
      family caregiver participated. RESULTS: Adherence with speech and language
      pathologists' dysphagia recommendations overall was over 50% in all but one case.
      For specific strategies, the highest adherence was observed for diet
      modifications of foods (89%), communication during the mealtime (83%), amount of
      food to present (81%), and the pacing of fluids and foods (81%). Lower levels of
      adherence were identified in relation to postural management (58%), environmental
      changes (58%), utensils (56%), and preparatory strategies (49%). CONCLUSIONS:
      Adherence with use of strategies to support mealtimes was over 50% in all but one
      case. Findings suggest that support is essential to promote safe mealtimes,
      reduce family carers' stress and increase knowledge, confidence, and adherence in
      implementing dysphagia guidelines in the family home. Implications for
      rehabilitation Difficulties with eating, drinking and swallowing (dysphagia) can
      impact on the parent-child mealtime experience. Mealtime strategies as
      recommended by a speech-language pathologist can support children who have
      difficulties eating, drinking, and swallowing. Some strategies to support eating,
      drinking, and swallowing are easier for carers to adhere to than others.

PMID- 30222369
TI  - Drug-induced bone loss: a major safety concern in Europe.
AB  - INTRODUCTION: Drug-induced bone loss remains the major cause of vertebral and hip
      fractures and significantly associated to morbidity and mortality. This article
      will review the common drugs identified as the causes of bone loss and the risk
      factors and management in European countries. Areas covered: Beyond glucorticoid 
      the most cause of osteoporosis, many different drugs could cause harmful
      skeletal disorders. The antiepileptics, hormonal therapy, GnRH antagonists,
      aromatase inhibitors are well-known cause of bone loss. Osteoporosis and
      fractures risk also increased with calcineurin inhibitors, antiretroviral drugs,
      selective inhibitors of serotonin reuptake, loop diuretics, heparins, oral
      anticoagulants, high doses of thyroxine and proton pump inhibitors. Expert
      opinion: Drugs are an important secondary cause of osteoporosis. Healthcare
      professionals should reassess the requirement for drugs and use the lowest dosage
      and shortest duration. Lifestyle changes, adequate calcium, vitamin D supplement,
      appropriate monitoring of bone status and initiating osteoporosis treatment if
      indicated are recommended when drugs having potential deleterious effects on bone
      are used, particularly in high risk patients. The update and further studies
      would provide concluded evidences of controversial drugs induced bone loss and
      determine the best prevention and treatment strategies.

PMID- 30222370
TI  - Acute Kidney Injury in Chinese HIV-Infected Patients: A Retrospective Analysis
      from the Intensive Care Unit.
AB  - To describe the epidemiology, outcomes, and risk factors of acute kidney injury
      (AKI) among human immunodeficiency virus (HIV)-infected patients admitted to the
      intensive care unit (ICU).We reviewed all the HIV-infected admissions to the ICU
      at Beijing Ditan hospital in the time span from June 2005 to May 2017 and
      collected demographic, clinical, and laboratory data for our sample. AKI was
      diagnosed and classified according to the Kidney Disease Improving Global
      Outcomes (KIDIGO) criteria. We analyzed the incidence of AKI and its associated
      mortality. The potential risk factors for severe AKI were also investigated in
      this study. A total of 225 HIV-infected patients were included in the final
      analysis. The incidences of no-AKI, AKI stage 1, AKI stage 2, and AKI stage 3,
      were 46.2% (104), 19.1% (43), 8.4% (19), and 26.2% (59), respectively. By
      logistic regression analysis, severe AKI (stages 2-3) was an important predicator
      for 60-day mortality with an odds ratio of 4.234. By multivariate analysis, a
      high acute physiology and chronic health evaluation, version II (APACHE-II) score
      (p = 0.024), low albumin (p < 0.031) at the first 24-h admission ICU, shock (p =
      0.013), and bloodstream infection (p = 0.006) during hospitalization were all
      found to be significant risk factors for severe AKI. AKI is common in HIV
      infected patients admitted to the ICU, and the mortality of patients with AKI
      stages 2-3 is significantly higher compared with those without such conditions. A
      high APACHE-II score and a lower albumin level at the first 24-h admission to ICU
      are significant predictors of severe AKI in this specific population. Shock and
      bloodstream infection during hospitalization can also lead to severe AKI.

PMID- 30222371
TI  - The Phosphate Content of Prescription Medication: A New Consideration.
AB  - BACKGROUND: Phosphate restriction is needed in most dialysis patients. The
      package inserts from some medications indicate that phosphate may be part of the
      excipient fraction of drugs. It is unclear whether its amount may be clinically
      significant since the phosphate content is unquantified. METHODS: We reviewed the
      package inserts for the branded formulations of the most widely used drugs at a
      dialysis chain. We measured the phosphate levels in a sample of the branded form
      of these drugs and some of their generic formulations. We also reviewed the
      available package inserts of 16 selected generic drug manufacturers for the
      presence of phosphate in drugs that were phosphate free in their branded
      formulation. RESULTS: We identified 12 prescription products that contained
      phosphate, 9 of which contained clinically significant quantities (>10 mg per
      daily dose) notably in both branded and generic forms of amlodipine, lisinopril,
      paroxetine and bisoprolol. Phosphate was rarely present in a generic drug when
      its corresponding branded formulation was phosphate free. CONCLUSION: Commonly
      prescribed drugs may contain clinically important levels of phosphate.

PMID- 30222372
TI  - Oligonucleotide-Based Drug Development: Considerations for Clinical Pharmacology
      and Immunogenicity.
AB  - The field of oligonucleotide (OGN)-based therapeutics has been growing
      dramatically in the past decade, providing innovative platforms to develop agents
      for the treatment of a wide variety of clinical conditions. OGN agents have
      unique physicochemical properties and pharmacokinetic/pharmacodynamic
      characteristics. This review considers findings from the literature and
      information on new molecular entities submitted to the US Food and Drug
      Administration as OGN-based therapeutics. In addition, the article discusses
      several challenging issues from the perspective of clinical pharmacology,
      emphasizing the potential of immunogenicity, the effect of renal impairment on
      OGN exposure, drug-drug interactions, and the utility of
      pharmacokinetic/pharmacodynamic modeling. The field of OGN-based therapeutics is
      in evolution and will benefit from further studies as well as clinical experience
      to formulate guidelines and promote the development of this class of agents.

PMID- 30222373
TI  - Generational Value Differences Affecting Public Perceptions of and Willingness to
      Participate in Clinical Trials.
AB  - BACKGROUND: It is widely acknowledged that patient recruitment is a significant
      challenge and represents one of the primary reasons for drug development delays.
      Data from the Center for Information and Study on Clinical Research Participation
      (CISCRP) "Perceptions & Insights" study indicate that the 18- to 34-year-old
      Generation Y subgroup was the least willing to participate in a clinical trial.
      METHODS: The willingness of Generation Y to participate in clinical studies was
      compared to that of older groups in the CISCRP study. These results were then
      compared to data from earlier studies. RESULTS: Statistically significant
      differences existed between the willingness of Generation Y to participate in
      clinical studies when compared to older age groups. Generational perceptions and
      value differences were explored via corporate and sociological research findings
      to determine why disparities existed among age groups regarding the willingness
      for clinical trial participation. CONCLUSIONS: Preliminary results indicate that
      members of Generation Y are less willing to participate in clinical studies and
      that these differences are truly generational and not simply age related.

PMID- 30222374
TI  - Risk-Based Monitoring: A Closer Statistical Look at Source Document Verification,
      Queries, Study Size Effects, and Data Quality.
AB  - BACKGROUND: Data quality within the clinical research enterprise can be defined
      as the absence of errors that matter and whether the data are fit for purpose.
      This concept, proposed by the Clinical Trials Transformation Initiative, resulted
      from a culmination of collaboration with industry, academia, patient advocates,
      and regulators, and it emphasizes the presence of a hierarchy of error types,
      resulting in a more efficient and modern data-cleaning paradigm. While source
      document verification (SDV) is commonly used as a quality control method in
      clinical research, it is disproportionately expensive and often leads to
      questionable benefits. Although the current literature suggests that there is a
      need to reduce the burden of SDV, there is no consensus on how to replace this
      "tried and true" practice. METHODS: This article proposes a practical risk-based
      monitoring approach based on published statistical evidence addressing the impact
      of database changes subsequent to SDV. RESULTS: The analysis clearly demonstrates
      minimal effects of errors and error corrections on study results and study
      conclusions, with diminishing effect as the study size increases, and it suggests
      that, on average, <8% SDV is adequate to ensure data quality, with perhaps higher
      SDV rates for smaller studies and virtually 0% SDV for large studies.
      CONCLUSIONS: It is recommended that SDV, rather than just focusing on key primary
      efficacy and safety outcomes, focus on data clarification queries as highly
      discrepant (and the riskiest) data.

PMID- 30222375
TI  - Are Phase 3 Clinical Trials Really Becoming More Complex?
AB  - BACKGROUND: This study uses the data from many of the mandatory fields in
      ClinicalTrials.gov to examine changes, possibly leading to more complexity in the
      design and execution of commercially sponsored phase 3 clinical trials. METHODS:
      In this analysis we compare baseline year 2008 data, when a broad number of the
      protocol/study design and execution variables became mandatory, with the data
      from the last full year of results, 2013. RESULTS: There has been relatively
      little change in the protocol and study design over the years covered in this
      study. The most pronounced change is associated with single-patient duration:
      there is a significant increase in the period of time a patient is treated in the
      study protocol. The study also highlights an important methodological issue: many
      of the claims in print about complexity have yet been substantiated through the
      use of peer-reviewed data or in settings where others can interrogate the
      results. CONCLUSIONS: In general, there is limited evidence for significant
      increases in the study and protocol design and execution of phase 3 clinical
      trials sponsored by pharmaceutical companies.

PMID- 30222376
TI  - Quantitative Methods for the Identification of Signals for Individual Case Safety
      Reports in India.
AB  - BACKGROUND: The Pharmacovigilance Programme of India (PvPI) is responsible for
      collecting reports of adverse drug reactions (ADRs) to assess the association
      between particular drugs and ADRs. The aim of the present study was to apply
      statistical tools to determine associations between drugs and ADRs for signal
      detection in the PvPI. METHODS: Four methods were proposed for quantitative
      signal detection: one was based on Bayesian inference and others on classical
      inference procedures. The effectiveness of the proposed methods was assessed by
      applying them to 4 drug-ADR combinations. RESULTS: The proposed methods were easy
      to apply and relevant to the Indian context. In selected methods, the information
      component value was more specific, whereas the proportional relative risk was
      more sensitive. CONCLUSIONS: The proposed methods may help in the identification
      of new signals in Indian individual case safety reports.

PMID- 30222377
TI  - An Examination of eClinical Technology Usage and CDISC Standards Adoption.
AB  - BACKGROUND: The Tufts Center for the Study of Drug Development (Tufts CSDD)
      collaborated with the Clinical Data Interchange Standards Consortium (CDISC) on a
      joint working group study with 10 participating companies including
      biopharmaceutical, CROs, and eClinical technology vendors. The objective of the
      study was to examine current and projected use of eClinical technology and
      standards across respondent organizations and in clinical studies and to gather
      perceptions and attitudes about technology and standards adoption. METHODS: The
      Tufts CSDD study examined the use of eClinical technology and CDISC standards
      through a comprehensive survey combined with analyses of clinical study data
      among biopharmaceutical companies and contract research organizations. RESULTS:
      The results suggest increasing use of specific eClinical technology solutions and
      standards. The barriers to adoption of eClinical trial tools are addressed as
      well as the benefits of standards adoption. Differences between respondent
      perceptions and actual study data are examined, and the survey results are
      compared with those from prior studies. CONCLUSIONS: The results of the study
      indicate that increasing use of standards could translate into improvements in
      time, costs, and overall approval rates. The study also observed an uptake in the
      use of eClinical technologies that could potentially create efficiencies and
      streamline operational processes.

PMID- 30222379
TI  - Managing Team Innovation in the Research and Development (R&D) Organization:
      Critical Determinants of Team Effectiveness.
AB  - BACKGROUND: Teams are the principal vehicle in developing new drug development
      strategy and executing the tasks required to accomplish those objectives. The key
      research questions related to the measurement of team innovation performance in
      the branded pharmaceutical industry and identification of the drivers for optimal
      team performance outcomes. This project evaluated the key drivers for team
      innovation performance (defined as "outcomes"). Team outcomes included new
      information creation, compression of development time, expansion of image,
      learning, capability development, growth satisfaction, and overall effectiveness.
      METHODS: A total of 13 questions, with multiple subparts, as part of 7 key
      dimensions were adapted from previously validated scales. Eligible participants
      were those who were employed in a pharmaceutical R&D organization and were a
      member of a drug discovery and/or development team. Survey respondents were
      prompted to respond to the degree they agreed or disagreed using 5- to 7-point
      Likert-type scales. All analyses (reliability tests, factor analysis, and
      multivariate regression) were performed in IBM SPSS v22. RESULTS: While good
      correlations individually existed between team outcomes (dependent variable) and
      tested independent variables (autonomy, coaching, climate, proactive personality,
      empowering leadership, and transactive memory systems [TMSs]), the best
      predictors identified through multivariate regression analysis were leader and
      peer coaching and TMSs. CONCLUSIONS: This research offers key insights for
      managers when forming and staffing teams. One is an emphasis on coaching. It is
      imperative for senior managers to assign individuals to teams who liaise with
      broader management that are capable of offering coaching and availability for
      team members to enhance their skills. This is particularly important in a growing
      hypercompetitive environment that is witnessing continuous strategic change. A
      second area of emphasis is on TMS, in an expertise-centered organization. As this
      is a central driver to team performance, it is imperative to improve adaptation
      skills of team members.

PMID- 30222378
TI  - Improved Label and Liver Warning for Nonprescription Acetaminophen Products.
AB  - OBJECTIVE: To compare consumer preferences for a revised and current
      acetaminophen over-the-counter "Drug Facts" labels (ODFL) on warnings and self
      reported correct intended action following signs of overdose. METHODS: Adults
      visiting a community center were randomly assigned to revised or current ODFLs
      using previously reported label comprehension methodology. RESULTS: Participant
      (N = 110) ratings for both ODFLs were comparable for ease of finding and
      understanding information. In response to an emergent overdose scenario, the
      proportion reporting the correct intended action using the revised ODFL was
      significantly greater than the proportion using the current ODFL (91% [97.5% CI,
      0.82-0.99] vs. 76% [97.5% CI, 0.64-0.89]). In side-by-side comparisons, the
      revised ODFL was superior for overall consumer preference, usefulness for first
      time use, and better overdose-related directions. A revised bottle cap statement
      also outperformed the current statement used on brand acetaminophen. CONCLUSION:
      Findings support revision of acetaminophen ODFLs to improve liver damage warnings
      and to optimize labeling likely to be useful in prevention of and response to
      overdose.

PMID- 30222380
TI  - An Overview and Analysis Regarding the Use of Adjudication Methods in EU and US
      Drug Approvals.
AB  - BACKGROUND: Several regulatory guidelines recommend that assessments of endpoints
      supporting drug approval should be verifiable by applicants and the regulatory
      agencies to minimize the potential for bias. This becomes especially critical
      when assessments are not based on measurable data but are derived from the
      interpretation of measurements, when they require the application of complex
      endpoint assessments, or when a study cannot be blinded. To make such
      interpretation more robust, a verification of (subjective) assessments by an
      independent panel of experts is frequently utilized. The objective of this paper
      was to analyze how often adjudicated methods across efficacy and safety
      assessments were used in drug approvals in the European Union and United States
      in 2013 and early 2014. METHODS: A total of 35 new molecular entities (NMEs)
      approved by the US Food and Drug Administration (FDA) and 88 European Medicines
      Agency (EMA) approvals in Europe were included in this analysis. RESULTS: An
      adjudication method was used in phase III development programs in 69% of the NMEs
      approved in the United States and 41% of EMA approvals. Drugs developed for
      oncology and endocrinology typically used an independent review committee (IRC)
      in line with recommendations made in relevant regulatory guidance, whereas
      nervous systems, antivirals, and vaccines drugs typically did not. Central
      reading was most frequently used for efficacy endpoints or in a combination of
      efficacy endpoints and safety measures. Overall, approximately 20% to 30% of the
      primary endpoints analyzed in the US/EMA documentation were classified as
      subjective endpoints that were based on clinician-dependent (and subject
      dependent) assessments. The remaining 70% to 80% were more robust endpoints that
      were reviewed by a central committee and/or were based on objective (measurable)
      endpoints, including laboratory tests. CONCLUSION: While no one size fits all,
      the need to include an IRC depends on the subjectivity of the primary endpoint,
      the therapeutic area concerned, the clinical trial design, the need to assess
      reliability of marginal positive events, or if a critical assessment is required
      for adverse event accuracy.

PMID- 30222381
TI  - National Drug Information Sharing in the Thailand Health Care Supply Chain.
AB  - PURPOSE: The paper explores the problems of health care supply chain in Thailand.
      A national drug information database is designed and presented to facilitate drug
      information sharing. METHODS: Literatures are analysed in order to develop the
      information needed by stakeholders in health care supply chain. Expert interviews
      are conducted to verify the necessity of all of the attributes. A conceptual
      network of web-based services is designed. RESULTS: The study purposes the use of
      a national drug information database containing drug information needed by all
      players and enabling nationwide information exchanges in a standard electronic
      format. CONCLUSIONS: Due to fragmented data and information and lack of data
      standard problems, the study purposes the information sharing system by
      constructing a national drug information database. The database contains
      information needed by all players in health care supply chain. A conceptual
      network of web-based services is presented to facilitate drug information sharing
      among health care supply chain members as well nationwide implementation.

PMID- 30222382
TI  - Advances in Clinical Outcome Assessments.

PMID- 30222383
TI  - Overcoming Organizational Challenges of Integrating Patient-Reported Outcomes in
      Oncology Clinical Trials.
AB  - Patients with cancer frequently experience multiple symptoms that may cause
      significant distress and may impair physical, emotional, and social functioning
      and health-related quality of life. Drug development in oncology is characterized
      by a high attrition rate of new compounds, faster development times encouraged by
      the regulatory process, studies that are often open and single-arm, and emphasis
      on survival-related endpoints, creating unique challenges for the inclusion of
      patient reported outcomes (PROs). These challenges to include PRO-related
      endpoints in oncology research are further exacerbated by downward pressure on
      budget and resources and also an overly rigorous application of the US Food and
      Drug Administration's PRO guidance, which can in turn prevent study teams from
      optimally including PROs in oncology clinical trials. With increasing calls for
      demonstration of value of new cancer drugs from payers, patients, and their
      caregivers, study teams should consider the utility of PROs beyond regulatory
      needs. Optimal implementation of a PRO strategy in oncology research can be
      achieved by applying the PRO guidance to the greatest extent possible, making use
      of off-the-shelf PRO measures to capture concepts of interest, discussing plans
      with the regulatory bodies early in the process, and treating PRO-related
      endpoints with the same level of rigor as other endpoints.

PMID- 30222384
TI  - Optimizing Electronic Capture of Clinical Outcome Assessment Data in Clinical
      Trials: The Case of Patient-Reported Endpoints.
AB  - For a number of compelling scientific, operational, and regulatory reasons, the
      use of electronic data capture is becoming the preferred means of collecting
      clinical outcome assessment (eg, patient-reported outcome [PRO]) data in clinical
      trials. Electronic PRO (ePRO) data collection leverages screen-based technologies
      (eg, handheld devices, tablet computers, and web-based systems) and telephone
      based (eg, interactive voice response) systems. Data collection is routinely
      either site based (ie, clinical study site) or field based (eg, subject's home,
      school, or workplace). While tablet computers are often used for site-based PRO
      data collection, handheld devices have become the mainstay for ePRO data capture
      in field-based settings. The data collection devices are usually provisioned to
      the sites or subjects by an ePRO system provider contracted by the clinical trial
      sponsor. With site-based data collection, study staff are responsible for
      ensuring subject compliance with the protocol-driven data collection procedures,
      whereas with field-based data collection, the subject is responsible for
      compliance with the data entry requirements and sites are accountable for
      remotely monitoring the data for compliance. In addition to site and subject
      compliance issues, technology-related factors must be anticipated in order to
      adhere to the electronic PRO data collection plan. The objective of this paper is
      to describe study site-, subject-, and technology-related factors that may lead
      to deviations from the planned electronic collection of PRO data (eg, defaulting
      to paper-based data collection) and to provide recommendations aimed at
      preventing potential problems or quickly resolving problems once they occur.

PMID- 30222385
TI  - Statistical Considerations on the Evaluation of Imbalances of Adverse Events in
      Randomized Clinical Trials.
AB  - Adverse events (AEs) data compose the main body of safety data in clinical
      trials. Medically important imbalances of AEs in large double-blind randomized
      controlled trials (RCTs) are signals of potential adverse drug reactions. They
      will be further evaluated for causality and shape the initial label that gives
      users necessary information on the safe use of the drug. However, causality
      assessment in premarketing RCTs can be challenging. This article highlights key
      aspects that need attention and statistical analysis approaches that could be
      helpful for screening and evaluation of signals generated from imbalances of AEs
      in moderate or large RCTs.

PMID- 30222386
TI  - Considerations for Requiring Subjects to Provide a Response to Electronic Patient
      Reported Outcome Instruments.
AB  - The increase in the use of electronic patient-reported outcome (ePRO) instruments
      has presented study teams with considerations not previously encountered with
      paper. Specifically, in an effort to minimize missing data, there is now the
      opportunity of requiring subjects to provide a response to an item before
      allowing the subject to proceed to the next item. While the ability to require
      subjects to respond to ePRO items would seem to guarantee a complete data set, it
      raises questions about the conditions under which it is appropriate to require
      subjects to respond to the items in an instrument. This article provides guidance
      on the circumstances under which allowing a subject to opt out of responding to
      ePRO items may be appropriate. Three main scenarios are discussed: (1) requiring
      subjects to complete all items in all the instruments in the study, (2) allowing
      subjects to opt out of at least some selective items that do not support key
      primary or secondary endpoints, and (3) allowing subjects to opt out of
      responding to any or all items in the study. For either of the 2 scenarios
      allowing the subject to opt out of responding to an item, the use of programmed
      edit checks is highly recommended to confirm that the subject intended to "skip"
      or "opt out of" the item. This ensures that, at the end of the study, the
      database contains an explicit data point indicating when a subject has actively
      decided to skip an item. While this article is focused on patient-reported
      outcomes, the issues raised could also apply to other clinical outcome
      assessments, such as clinician- and observer-reported outcomes.

PMID- 30222387
TI  - Clinical, Ethical, and Socioeconomic Considerations for Prescription Drug Use
      During Pregnancy in Women Suffering From Chronic Diseases.
AB  - The increasing proportion of women conceiving later in life, associated with the
      higher probability of contracting a chronic disease, highlights an increasing
      need to understand the impact of drug use for chronic diseases pre- and
      postpartum. In this study, the authors report the results of systematic reviews
      of drug use during pregnancy by focusing on pregnant women with a chronic
      disease, specifically, epilepsy, rheumatoid arthritis (RA), or schizophrenia. The
      authors studied the clinical impact of drug use in these chronic diseases on the
      mother and fetus, as well as the ethical issues and socioeconomic impact of drug
      use during pregnancy for women with these conditions. The results indicate that
      treatment discontinuation in epilepsy and schizophrenia can lead to serious
      adverse effects, whereas pregnancy can have an ameliorating effect on RA
      symptoms. Delivery and neonatal complications were associated with the use of
      older generation drugs across the 3 diseases. Newer generation drugs were deemed
      safer but more expensive. Ethical considerations for physicians and patients
      involved mainly the potential risks of drug use for the fetus. In conclusion,
      treatment guidelines need to be developed in the future; additionally, better
      insight into the economics of pregnancy for women with chronic diseases will
      improve value for money in obstetric care.

PMID- 30222388
TI  - "Bring Your Own Device" (BYOD): The Future of Field-Based Patient-Reported
      Outcome Data Collection in Clinical Trials?
AB  - Field-based patient-reported outcome (PRO) assessments, including measures of
      signs, symptoms, and events that are administered outside of the research clinic,
      can be critical in evaluating the efficacy and safety of new medical treatments.
      Collection of this type of data commonly involves providing subjects with stand
      alone electronic devices, such as smartphones, that they can use to respond to
      assessments in their home or work environment. Although this approach has proven
      useful, it is also limited in several ways: For example, provisioning stand-alone
      devices can be costly for sponsors, and requiring subjects to carry a device that
      is exclusively dedicated to the study can be burdensome. The "Bring Your Own
      Device" (BYOD) approach, in which subjects use their own smartphone or Internet
      enabled device to complete field-based PRO assessments, addresses many of these
      concerns. However, the BYOD model has its own limitations that should be
      considered. In this article, representatives of the ePRO Consortium review
      operational, privacy/security, and scientific/regulatory considerations regarding
      BYOD. We hope that this review will allow researchers to make informed decisions
      when choosing methods to collect field-based PRO data in future clinical trials.
      Additionally, we hope that the discussion in this article will establish a
      research agenda for further examination of BYOD approaches.

PMID- 30222389
TI  - Advances in the Evaluation of Longitudinal Construct Validity of Clinical Outcome
      Assessments.
AB  - Historically, the assessment of longitudinal construct validity in the field of
      psychosocial measurement involved defining hypotheses and calculating correlation
      coefficients using scores based on 2 measures at 2 or more time points. In the
      context of patient-reported outcomes, this evolved into sensitivity to change and
      responsiveness, including the computation of effect size estimates of change,
      standardized response means, and indices such as Guyatt's statistic. Cross
      sectional analyses or analyses based on 2 time points have been the standard
      practice. Evolving conceptualizations have incorporated more than 2 time points
      and have included depictions of individual trajectories of change in multiple
      measures, structural equation models, and mixed modeling techniques. The focus of
      this article is on methods to evaluate longitudinal construct validity. We
      describe a sample of these methods and provide considerations and recommendations
      for designing a thoughtful longitudinal construct validity evaluation of clinical
      outcome assessments.

PMID- 30222390
TI  - Regulatory Definitions and Good Pharmacovigilance Practices in Social Media:
      Challenges and Recommendations.
AB  - Social media presents new challenges to the biopharmaceutical industry for
      conducting pharmacovigilance activities. The authors reviewed worldwide
      regulatory guidance documents related to monitoring of adverse events posted on
      social media sites and identified gaps in current regulatory definitions for
      pharmacovigilance. Points to consider for addressing these gaps are made to offer
      standards for industry consideration and a potential framework for guidance from
      global health authorities.

PMID- 30222391
TI  - The Relationship Between Development Start Lag and Approval Lag in Oncology Drug
      Development in Japan.
AB  - BACKGROUND: The delay of initiation of clinical development is considered a
      causes of delay of approval of drugs (drug lag) in Japan. METHODS: For oncology
      drugs newly approved between 2000 and 2012 in Japan, a possible impact of delay
      of initiation of clinical development (development start lag [DSL]) on delay of
      approval (approval lag [AL]) was investigated, focusing on the delay from the US
      timelines. The equation defining the relationship between the DSL and AL of 33
      oncology drugs was calculated by using simulation models, then the Pearson
      coefficient of correlation between parameters was calculated. RESULTS: From the
      analysis of all drugs investigated, a positive relationship between the DSL and
      AL was suggested. However, the relationship seemed to have 2 phases, including a
      flat phase, followed by a linearly increased phase with a breakpoint at 2340 DSL
      days (approximately 6.4 DSL years). CONCLUSIONS: Shortening the DSL is important
      for reducing large AL, but it is not necessary to eliminate the DSL completely
      for the purpose of minimizing the AL.

PMID- 30222392
TI  - Unique Challenges in Development, Psychometric Evaluation, and Interpretation of
      Daily and Event Diaries as Endpoints in Clinical Trials.
AB  - By bringing data collection closer to real time and minimizing recall bias,
      patient diaries or event-driven logs offer substantial benefits over
      retrospective questionnaires for many patient-reported disease concepts. Such
      assessments are increasingly used to support primary and secondary endpoints in
      randomized controlled trials. These diaries have the potential to provide more
      reliable and valid assessment of patients' subjective experiences of symptoms and
      disease events. However, use of such diaries presents significant and unique
      challenges depending on the context of use. Of note, while symptom-related label
      claims are those most frequently granted by regulatory authorities, no guidance
      specific to support the development, psychometric evaluation, and interpretation
      of endpoints derived from patient diaries exists. This article provides an
      overview of key methodological, statistical, and clinical considerations for
      implementation of patient diaries with a regulatory perspective in mind.
      Approaches and solutions covered in this article include (1) techniques to
      establish content validity based on obtaining qualitative insights in
      naturalistic settings and real-life experience of diary completion, (2)
      demonstration of psychometric properties with respect to day-to-day variability,
      and (3) aggregation of data from multiple days/events to move from items to
      endpoints. The importance of the patients' engagement is highlighted in order to
      help overcome these challenges throughout all stages of diary and endpoint
      development and evaluation. This article can inform researchers who are
      developing or implementing patient diaries as clinical trial endpoints to ensure
      that the nuances of this mode of data collection are considered in the
      development of endpoints and prior to regulatory interactions.

PMID- 30222393
TI  - The Ethics Around Drug Labels and Generic Medicines.

PMID- 30222394
TI  - Off-Label Promotion of Prescription Medicine: Is It Ever Justifiable?
AB  - Off-label promotion has attracted intense scrutiny from regulators in recent
      decades, resulting in many pharmaceutical companies paying hefty penalties for
      illegal marketing practices. At the same time, the pharmaceutical industry has
      accused governments of applying double standards by encouraging the use of
      cheaper off-label alternatives to registered treatments, and defended their
      "right" to promote off-label drugs on freedom of speech grounds. However, the
      debate about off-label promotion and the prescribing that results has largely
      failed to address the issue that really matters-what impact does off-label
      promotion and prescribing have on patients and the health system? This paper
      explores the benefits and problems with off-label prescribing to determine
      whether off-label promotion is ever justified and, if so, under what conditions.

PMID- 30222395
TI  - Analysis of Social Media Interactions Between Pharmaceutical Companies and
      Consumers: The Power of the "Like".
AB  - BACKGROUND: The way in which pharmaceutical companies are using social media is
      vitally important in staying competitive, but the way social media users respond
      is equally if not more important. This study aimed to evaluate the use of social
      media by the top 20 pharmaceutical companies and to determine how much consumers
      interacted with these posts. RESULTS: The top 20 pharmaceutical companies
      included in this study were present in varying degrees on Twitter, YouTube, and
      Facebook (90%, 70%, and 50%, respectively). A linear regression analysis between
      pharmaceutical company interactions and corresponding consumer interactions for
      each social media platform did not find a statistically significant association (
      r2 = 0.44, 0.49, and 0.22, respectively). CONCLUSION: In a descriptive review of
      the social media posts analyzed, this study found pharmaceutical company posts to
      relate to disease state awareness, business updates, and community outreach
      projects.

PMID- 30222396
TI  - Choosing Appropriate Metrics to Evaluate Adverse Events in Safety Evaluation.
AB  - Safety assessment and monitoring are critical throughout the life cycle of drug
      development. The evaluation of safety information, specifically adverse events,
      from clinical trials has always been challenging for a number of reasons, such as
      the unexpectedness and rarity of some important adverse events, the fact that
      some events can recur, and the events' variability in duration and severity. To
      accurately characterize and communicate the risk profile of a drug, the choice of
      metrics is critical. However, there seems to be a lack of consistency, clear
      guidance, and comprehensive recommendations on choosing metrics for assessing
      adverse events in clinical trials. This article reviews the common metrics and
      provides some recommendations.

PMID- 30222397
TI  - Benefit-Risk Evaluation and Decision Making: Some Practical Insights.
AB  - Pharmaceutical drugs and devices are increasingly evaluated by quantitative tools
      that combine benefit and risk. These tools vary by their limitations and
      desirable properties, which may confuse the decision-making process. Experts from
      the Food and Drug Administration (FDA) and industry shared their perspectives at
      the 2012 American Statistical Association (ASA) Biopharmaceutical Section FDA
      Industry Statistics Workshop, and these insights are presented here. First,
      benefit-risk terminology is given to better understand subtle distinctions. Next,
      pragmatic considerations in endpoint selection are given that distinguish between
      benefit-risk assessment and analysis of clinical trials. Then the strengths of
      weighting methods, including ranking, utilities, and risk tolerance for assessing
      the trade-off between benefits and risks, are compared. The last topic presented
      is summarizing information to ease the interpretation, transparency, and ability
      to support decisions. Benefit-risk methods are moving towards a unified paradigm
      to make selection of endpoints, weights, and metrics easier and more structured.
      This will lead to better decision-making based on a transparent assessment and
      clear interpretability.

PMID- 30222398
TI  - Treatment Outcomes of Nevirapine- Versus Efavirenz-Based Highly Active
      Antiretroviral Therapy Regimens Among Antiretroviral-Naive Adult Patients in
      Ethiopia: A Cohort Study.
AB  - BACKGROUND: Despite wide use of nevirapine- and efavirenz-based highly active
      antiretroviral therapy regimens in Ethiopia, their treatment outcome has not been
      well studied. The objective of this study was to compare treatment outcome of
      nevirapine- and efavirenz-based regimens. METHODS: This retrospective cohort
      study was conducted on antiretroviral-naive adult patients with human
      immunodeficiency virus (HIV) who had started antiretroviral therapy. Study
      participants were excluded after treatment failure, regimen change, loss to
      follow-up, or transfer to other health facility. The outcomes of interest
      included immunologic recovery, immunologic failure, clinical failure, and
      treatment failure. RESULTS: There were 1064 HIV patients in the study; an equal
      proportion (1:1) from both efavirenz- and nevirapine-based regimens was included.
      Patients in both regimens had similar baseline CD4 cells count ( P = .876). In
      multivariate analysis, efavirenz-based regimens showed more likelihood of
      immunologic recovery, whether defined as a CD4 cell count of >200 cells/mm3
      (hazard ratio [HR] = 1.31 [95% CI, 1.05-1.59]), >350 cells/mm3 (HR = 1.26 [95%
      CI, 1.08-1.47]), or >500 cells/mm3 (HR = 1.95 [95% CI, 1.57-2.41]). Moreover,
      efavirenz-based regimens showed a lower hazard of treatment failure (HR = 0.66
      [95% CI, 0.49-0.88]). CONCLUSION: Although the finding of retrospective study
      should be interpreted with caution, efavirenz-based regimens were associated with
      superior treatment outcome.

PMID- 30222399
TI  - Medication Guide Reading Behaviors and Attitudes Among Subjects With Migraine,
      Asthma, or COPD.
AB  - BACKGROUND: This cross-sectional survey describes attitudes and reading behaviors
      toward medication guides among 785 subjects with migraine, asthma, or COPD who
      reported recent use of Treximet (sumatriptan/naproxen sodium) or Advair
      (fluticasone propionate/salmeterol). RESULTS: The survey demonstrated that the
      majority (82%) of subjects had read their medication guide, but most read it
      exactly once and did not read it thoroughly. Patients did not read medication
      guides with each refill, with the most frequent reasons being that they did not
      expect the information to have changed and that a doctor would tell them what
      they needed to know. Factors significantly associated with patients
      hypothetically being more likely to read medication guides associated with their
      new prescription included increasing age, simplification to format and content of
      the medication guide, and where subjects typically received their medication
      safety information. Patients reported acquiring medication safety from doctors or
      pharmacists more frequently than from medication guides. CONCLUSIONS: The results
      provide insights into potential revisions to the medication guides that may
      improve reading behaviors.

PMID- 30222400
TI  - Lessons Learned From Hundreds of Thorough QT Studies.
AB  - BACKGROUND: The coherence between the relationship of QTc and drug plasma
      concentration (this relationship is measured through the slope) and ICH E14
      findings based on hundreds of QT study reports was studied. RESULTS: Based on ICH
      E14 analysis, our findings indicate that if the slope was not positive, in most
      cases (86%) the corresponding QT studies were also negative. If the slope was
      positive, 92% of the corresponding QT studies were also positive. CONCLUSIONS: In
      exploring whether a thorough QT (TQT) study may be needed, we recommend that the
      relationship analysis between QTc and drug plasma concentration be performed when
      proper single ascending dose (SAD) and multiple ascending dose (MAD) studies are
      available. If the relationship cannot be detected and the 90% upper confidence
      interval at a fixed concentration level (50th or 75th percentile, or mean peak
      plasma concentration [Cmax]) is below a certain threshold level (eg, 10
      milliseconds), then a TQT study might be unnecessary. If the relationship can be
      established and the 90% lower confidence interval at a fixed concentration level
      (eg, mean Cmax) is greater than 10 milliseconds, further investigation is needed.
      If the signal is real, one might choose intensive safety monitoring during later
      drug development instead of a TQT study for a good compound. However, there are
      still some gray areas in which this analysis alone cannot determine the potential
      QT liability of the drug, and a TQT type of study might be worth considering.

PMID- 30222401
TI  - The Life Sciences Translational Challenge: The European Perspective.
AB  - In recent years, concern has been growing that traditional research and
      development models in the life sciences are unsustainable. Productivity,
      especially in pharmaceuticals, has plummeted, and too many of the products
      emerging from increasingly lengthy and costly clinical development offer marginal
      benefit to patients. Although the phenomenon is global, there are specific and
      important features of European life sciences that impede the translation of an
      ever more penetrating understanding of biology into effective treatments. This
      article analyzes these issues in the context of European biopharmaceutical
      innovation, describes the actions that Europe is already taking, and suggests
      what more needs to be done.

PMID- 30222402
TI  - Pharmaceutical Ethics Comes to Life in Therapeutic Innovation & Regulatory
      Science.

PMID- 30222403
TI  - Ethical Considerations for Increased Transparency and Reproducibility in the
      Retrospective Analysis of Health Care Data.
AB  - In the field of health care, researchers and decision makers are increasingly
      turning toward retrospective observational studies of administrative claims and
      electronic health record databases to improve outcomes for patients. For many
      important questions, randomized studies have not been conducted, and even when
      they have been, such studies often inadequately reflect the realities of
      patients' lives or care. However, use of retrospective studies not only increases
      methodological complexity but also requires more subjectivity for those
      attempting to perform statistical analysis. The hurdles for establishing the
      reproducibility of such research to ensure accuracy and generalizability are
      therefore also higher, as are the requirements for transparency to limit the
      impact of bias. The ethical statistical practitioner will therefore need to take
      additional steps to enable results to be interpreted and acted upon with
      confidence. These include increased transparency regarding the impact of database
      selection, database quality, database content, and design decisions on the
      robustness of statistical conclusions. A number of approaches to increase the
      reproducibility of retrospective health care research are also presented, along
      with some discussion regarding responsibilities of data owners, statistical
      practitioners, publishers, and users of results.

PMID- 30222404
TI  - Medicines in Pregnancy Forum: Proceedings on Ethical and Legal Considerations.
AB  - To raise awareness and promote dialogue leading to action, this article provides
      proceedings on ethical and legal considerations associated with medicine use
      during pregnancy discussed during the 2014 DIA Medicines and Pregnancy Forum. A
      key focus of discussion at the forum was "When is it ethically appropriate to
      include or unethical not to include pregnant patients in clinical studies, and
      how can ethical barriers be addressed?" Also debated was the question "What are
      the most appropriate methods to collect and share data on medication use in
      pregnancy, and what is the best process for sharing such information?" Goals of
      the forum were to gain participant alignment on answers to these ethical
      questions, offer rationale for the answers, and provide insight into which
      stakeholders might be needed to facilitate discussion and action. Participants
      felt that under the right circumstances, drug research in pregnant women is
      justified and necessary. Multiple ideas and opinions on the handling of pregnant
      patients in clinical research, treating pregnant women in clinical practice, and
      communicating data to physicians and patients are presented.

PMID- 30222405
TI  - Improving the Legitimacy of Medicines Funding Decisions: A Critical Literature
      Review.
AB  - Many health care systems globally provide publicly subsidized access to
      prescribed medicines. Decisions about which medicines to fund affect a range of
      stakeholders, and it is not reasonable to expect that medicines funding decisions
      are supported by all stakeholder groups all the time. A more realistic aim may be
      for decisions to be understood and accepted as legitimate by stakeholders;
      however, several shortcomings of existing processes make it difficult to achieve
      this aim. To date, the main strategy to address these shortcomings has been to
      increase stakeholder involvement in decision making, either by eliciting
      stakeholder values or increasing stakeholder participation in decision making.
      Despite these efforts, there is growing evidence that decision makers are falling
      short when it comes to the perceived legitimacy of their resource allocation
      processes and decisions. As such, there is a pressing need for decision makers to
      think seriously and creatively about ways to increase the legitimacy of their
      processes and to make them more acceptable to a wider range of stakeholders. In
      this article we summarize and critique existing literature on the legitimacy of
      public resource allocation processes, and we make some practical suggestions for
      those who are concerned about this issue.

PMID- 30222406
TI  - Focus on Health Literacy: Recommendations to Improve European Union Risk
      Management Plan Public Summaries.
AB  - BACKGROUND: The complexity of drug risk information often exceeds patients'
      abilities to understand and effectively act on it. METHODS: The authors evaluated
      a layperson-focused European Union Risk Management Plan Public Summary and
      revised it to improve its understandability and usability by applying health
      literacy principles. The Suitability Assessment of Materials was used to test the
      appropriateness of the document for readers with low-to-average literacy levels.
      Two rounds of usability tests were conducted with American adults who had low to
      average education levels to identify areas of confusion. Revisions were made
      within perceived regulatory constraints. RESULTS: A number of health literacy
      principles can be applied to improve the understandability and usability of the
      document; however, the document contains many inherently complex concepts.
      CONCLUSIONS: The authors recommend that stakeholders reassess the intended use of
      the document by members of the public and rethink its scope and structure, with
      close involvement of patients and caregivers.

PMID- 30222407
TI  - Confounding Issues in Cancer Progress-The Impact of Investor Requirements on
      Senior Management Compensation and Regulatory Decisions: Tivozanib and Aveo
      Pharmaceuticals.
AB  - Previous research has demonstrated that profits are a key requirement in private
      pharmaceutical development. We sought to examine the extent that pressure of
      financial incentives exerted by investors and the board of directors, including
      senior management financial rewards, have on regulatory decisions made by senior
      management. Our selected case study involved Aveo Pharmaceuticals Inc (Aveo). The
      specific question was to what extent the terms of financing, particularly the
      corporate governance goals which determined executive bonus compensation, may
      have dictated Aveo's regulatory approach in the drug application process for
      tivozanib. These corporate governance goals emphasized quantitative over
      qualitative goals for the executive team. Aveo did not conduct the second arm of
      the randomized crossover trial, whose results could possibly have demonstrated a
      favorable clinical profile or a superior competitor's product. Arguably, as a
      result of this decision, the participating research subjects were denied an
      opportunity for improvement, and progress in the study of renal cell cancer was
      curtailed.

PMID- 30222408
TI  - Pre-Investigational New Drug Meetings With the FDA: Evaluation of Meeting Content
      and Characteristics of Applications for New Drug and Biologic Products.
AB  - INTRODUCTION: Prior studies suggested that holding preinvestigational new drug
      application (PIND) meetings with FDA has a positive effect on clinical
      development time (CDT). METHODS: New product marketing applications submitted to
      FDA CDER during fiscal years 2008-2012 were assessed for whether a PIND meeting
      was held and, if so, a qualitative assessment of meeting content was performed.
      RESULTS: Discussions contained in the PIND meeting minutes tended to reflect
      topics appropriate to an early phase of drug development, including chemistry,
      manufacturing, and controls (CMC) and safety topics (eg, nonclinical and clinical
      domains). Additionally, FDA commonly provided additional advice most often in the
      clinical and CMC domains. Applications for which a PIND meeting was held during
      drug development had shorter CDTs than those that did not. CONCLUSIONS: This
      analysis showed the importance of early communication with FDA during
      development, and small companies with limited regulatory experience may gain the
      greatest benefit from early communication with FDA.

PMID- 30222410
TI  - The Challenge Is Translation.

PMID- 30222409
TI  - Early Clinical Development Planning via Biomarkers, Clinical Endpoints, and
      Simulation: A Case Study to Optimize for Phase 3 Dose Selection.
AB  - BACKGROUND: This study investigated a framework that leverages the relationship
      between biomarkers and a target clinical endpoint to optimize an early
      development plan. METHODS: Different biomarker designs were assessed for proof of
      concept (PoC) and dose finding (DF) to improve phase 2b (Ph2b) design as well as
      phase 3 (Ph3) dose choice. A case study using a Bayesian trivariate normal
      distribution model for 2 biomarkers and a clinically relevant endpoint was
      utilized with simulation to assess performance characteristics. RESULTS: We found
      the following: (1) at typical sample sizes for early development trials,
      biomarkers appear useful for PoC but not for clinical endpoint DF; and (2) even
      with large amounts of prior information and near perfect correlation between
      biomarkers and clinical endpoints, Ph2b variability is only overcome by increased
      Ph2b sample sizes to improve Ph3 dose choice. CONCLUSIONS: For highly variable
      clinical endpoints, the fastest path should be to demonstrate PoC by biomarkers
      and then go directly to Ph2b to measure the target clinical endpoint.

PMID- 30222412
TI  - Actions of the National Regulatory Authorities in 10 Low- and Middle-Income
      Countries Following Stringent Regulatory Authority Safety Alerts on
      Rosiglitazone.
AB  - On September 23, 2010, the US Food and Drug Administration and the European
      Medicines Agency issued safety alerts for medicines containing rosiglitazone. The
      authors monitored the actions of national regulatory authorities (NRAs) from 10
      low- and middle-income countries to identify the time lag between the issuance of
      safety alerts by these two stringent regulatory authorities and any actions by
      these select NRAs. Two NRAs outside Africa took regulatory actions related to
      safety of rosiglitazone within 2 weeks of stringent regulatory authority safety
      alerts. For the 7 of the 8 African NRAs where the authors could confirm the date
      of regulatory action, the median time lag before some regulatory action was 43
      days, although there was considerable variability in time to regulatory action.
      Low- and middle-income countries should create or strengthen systems for timely
      consideration and management of emerging safety issues for products that they
      have registered.

PMID- 30222411
TI  - General Principles for the Education and Training of GCP Inspectors: The Outcome
      of Discussions by International Regulatory Experts in the Discussion Group on the
      ICH E6 Guideline.
AB  - In response to the globalization of drug development, regulatory inspection of
      Good Clinical Practice (GCP) has recently been conducted not only by
      International Conference on Harmonisation (ICH) regions but also non-ICH regions.
      To promote the international implementation of GCP, consistent understanding and
      interpretation of its concept among regions are important. This article
      summarizes the background and past activities of the E6 Discussion Group,
      established under the Regulators Forum.

PMID- 30222414
TI  - Introducing Internet Retailing of OTC Drugs in Japan: Revision of the
      Pharmaceutical Affairs Law.
AB  - Only the low-risk category of over-the-counter (OTC) drugs was permitted to be
      sold via the Internet, which was stipulated by the ordinance of the Minister of
      Health, Labour and Welfare under the Pharmaceutical Affairs Law in Japan. Two
      Japanese retailers of OTC drugs, who want to retail OTC drugs via the Internet,
      launched proceedings against the rule, and the Supreme Court gave a decision that
      the ministerial ordinance is illegal and invalid. The Ministry of Health, Labour
      and Welfare immediately started discussion to make rules for Internet retailing
      of OTC drugs. Finally, a bill designed to enable Internet retailing of OTC drugs
      was passed by the Diet on December 5, 2013, and the act was promulgated on
      December 13. The act was enforced on June 12, 2014. This article briefly touches
      on the decision process and also illustrates the key points of the new rules for
      Internet retailing.

PMID- 30222413
TI  - The First Paediatric Use Marketing Authorisation: A Case Study.
AB  - The first Paediatric Use Marketing Authorisation was approved in Europe in 2011.
      This article describes the assessment procedure and the key regulatory issues
      that were addressed.

PMID- 30222415
TI  - ClinicalTrials.gov: An Underutilized Source of Research Data About the Design and
      Conduct of Commercial Clinical Trials.
AB  - Since 2007, the US federal government has required that organizations sponsoring
      clinical trials with a least one site in the United States submit information on
      these clinical trials to an existing database: ClinicalTrials.gov . Over time,
      the number of mandatory variables has grown and will probably continue to grow.
      The database now represents an important source of descriptive information about
      the landscape for clinical trials. In addition, it constitutes a rich pool of
      data to test hypotheses-for instance, what variables are associated with an
      organization's ability to correctly estimate study completion times or complete
      those studies in as short a time frame as possible. This paper concludes that for
      mandated variables that the authors have labeled study identification, protocol
      and study design, and study execution, the data set constitutes a potentially
      very valuable research resource. With the exception of some site-related
      information, incomplete data did not exceed 3%. The incomplete site data are
      concentrated in several companies, so it is not unreasonable to assume that those
      data will also become more complete.

PMID- 30222417
TI  - openFDA: An Open Question.

PMID- 30222416
TI  - Challenges in the Development of Drug/Device and Biologic/Device Combination
      Products in the United States and European Union: A Summary From the 2013 DIA
      Meeting on Combination Products.
AB  - Compared with single-entity treatments, multientity or combination products have
      the potential to provide enhanced therapeutic utility. Because they involve
      components that would normally be overseen by different branches of health
      authorities (eg, different FDA centers), they raise numerous scientific,
      regulatory, policy, and review management challenges. This article summarizes the
      current status of the evolving combination product development landscape and
      potential options to address key challenges facing combination product
      developers. Continued collaboration and transparency among regulators,
      combination product developers, and other stakeholders is essential to
      streamlining the global combination product development and review process to
      ensure the availability of high-quality new products that are being used in a way
      that is safe and effective.

PMID- 30222418
TI  - Adverse Event Detection and Labeling in Pediatric Drug Development:
      Antiretroviral Drugs.
AB  - BACKGROUND: Pediatric safety studies are conducted for drugs undergoing
      development for use in pediatric patients. The objective of this study was to
      describe safety studies and compare adverse events of antiretroviral drugs
      between pediatric patients and adult subjects. METHODS: Pediatric and adult
      adverse event data were obtained from US Food and Drug Administration (FDA)
      approved drug labels for 9 antiretroviral drugs with pediatric indications
      approved by the FDA prior to 2013. For adverse events (AEs) reported in both
      pediatric patients and adult subjects, the risk difference (RD) and associated
      confidence interval (CI) were calculated. RESULTS: Of 35 drug-AE combinations, 10
      AEs were reported at statistically significantly ( P < .05) higher incidence
      rates in the pediatric population than in the adult population, and 3 AEs were
      reported at statistically significantly higher rates in the adult population than
      in the pediatric population. The largest differences where the risk of an AE was
      greater in pediatric patients than in adult subjects were for rash with efavirenz
      (RD = 36.24% [95% CI, 21.1 to 50.53]), diarrhea with efavirenz (RD = 24.53% [95%
      CI, 9.06 to 39.57]), and rash with nevirapine (RD = 16.14% [95% CI, 9.7 to
      24.27]). The largest differences where the risk of an adverse event was lower in
      pediatric patients than in adult subjects were for headache with abacavir (RD = 
      12% [95% CI, -16.81 to -6.89]), diarrhea with tipranavir (RD = -11.32% [95% CI, 
      15.02 to -5.6]), and diarrhea with lamivudine (RD = -9.88% [95% CI, -15.91 to 
      3.98]). CONCLUSIONS: The adult adverse event experience provides preliminary data
      for pediatric drug safety, yet the specific types of adverse effects and
      frequencies may not be predicted in children based exclusively on adults. As
      adult safety data do not fully inform the pediatric safety profile, pediatric
      safety studies should continue to be conducted separately for drugs undergoing
      testing in pediatric patients.

PMID- 30222419
TI  - A Trial Activation Initiative to Accelerate Trial Opening in an Academic Medical
      Center.
AB  - Delays in trial opening should be considered critical for the sake of not only
      the sponsor but the patients, as they may result in inequities of care. The Asan
      Medical Center, in Seoul, Korea, implemented a trial activation initiative in
      July 2012, in an aim to expedite the trial initiation timeline. Time intervals
      between trial initiation steps and the rate of institutional review board (IRB)
      and clinical trial agreement (CTA) parallel submission were assessed. A higher
      rate of parallel IRB and CTA submissions was observed after initiative
      implementation (25.5% vs 52.3%; P < .001). Initiative applications were shown to
      significantly accelerate the median trial opening time, from 114 to 81 days ( P <
      .001). Strategic processing of parallel submissions greatly shortened the median
      time required for trial initiation from 117 to 61 days compared with sequential
      submissions ( P < .001). A trial activation initiative including parallel IRB and
      CTA submissions is an effective tool for accelerating trial commencements.

PMID- 30222420
TI  - Principled Structured Incorporation of Clinical Knowledge Into Strategic
      Development Decisions.
AB  - Efficient use of limited pharmaceutical product development resources requires
      integrating multiple attributes, such as efficacy, safety, pharmacology, and so
      on, to decide at any stage whether the development of a product should proceed
      aggressively or slowly or be terminated. The decision process proceeds most
      effectively when the knowledge and experience of a product development team are
      transparently and reproducibly integrated with the findings from completed
      experiments and trials. In this article, the authors describe an approach for
      quantitatively and objectively assessing evidence at any stage of development,
      one based on a mathematical combination of sets of pairwise comparisons. The
      attributes of the process and the rules for combining its elements to guide
      decisions are determined by the project team and other stakeholders before
      obtaining the determinative data to facilitate exploration of the sensitivity of
      a recommended action to various assumptions. Its statistical properties can be
      evaluated with standard statistical decision analysis methods.

PMID- 30222421
TI  - Implementing a Process to Review Product-Specific Misinformation in Online Drug
      Information Compendia.
AB  - Health care professionals and consumers often use online drug information
      compendia, which are intended to be user-friendly, readily available, accurate,
      and up-to-date. While these resources can be valuable, it has been shown that
      some compendia contain inaccuracies and outdated information, motivating the
      Medical Services (medical information) Department at Purdue Pharma LP to
      implement a periodic, standardized review of select online drug information
      compendia. Monographs within compendia for up to 9 Purdue products were reviewed
      and compared to their current Full Prescribing Information, with a focus on
      identifying safety-related misinformation. Content correction requests for nearly
      1000 errors were submitted to 7 compendia clinical editors. This surprisingly
      large number of errors highlights the need for compendia to better maintain
      accurate product monographs, as well as for pharmaceutical companies to
      proactively and periodically review them for misinformation. Based on these
      findings, an overview on how the pharmaceutical industry may implement a drug
      information compendia review process is provided.

PMID- 30222422
TI  - Global Regulatory Dissonance: A Case Study of Industry Views on the Development
      of Drugs for Postmenopausal Osteoporosis.
AB  - BACKGROUND: The footprint of drug distribution is multinational, but the
      regulatory frameworks supporting drug development, review, and approval remain
      largely regional. As a result, industry faces regulatory standards that may be
      complementary, additive, or contradictory, resulting in global regulatory
      dissonance (GRD). METHODS: Global regulatory dissonance was explored through a
      case study of drug development (postmenopausal osteoporosis) using survey
      methodology. RESULTS: In the feedback received, respondents generally agreed that
      GRD increases the complexity, timelines, and size of registration studies.
      Dissonant regulatory feedback on proposed labeling, applications, and benefit
      risk assessments was also reported. Multiple causes of GRD were identified,
      including dissonant drug regulatory authority advice, guidelines, benefit-risk
      assessments, drug approval precedents, medical standards of care, and health
      technology assessments. Harmonization of guidelines, scientific advice, benefit
      risk procedures, and expanded use of mutual recognition agreements were
      identified as mechanisms thought to reduce GRD. CONCLUSIONS: The results suggest
      that global access to new drugs may be enhanced through a greater understanding
      of GRD.

PMID- 30222423
TI  - Breakthrough Therapy Designation: Bringing Innovation Swiftly to Patients.
AB  - In early 2012, the Breakthrough Therapy Act was introduced into the US House of
      Representatives and the Senate. The bills received bipartisan support and were
      included as an amendment to the Food and Drug Administration Safety and
      Innovation Act in the Prescription Drug User Fee Act V. On July 9, 2012, the
      breakthrough therapy designation was signed into law. As of June 13, 2014, a
      total of 48 products have been designated as breakthrough therapies by the Center
      for Drug Evaluation and Research, and 4 of those have received FDA new molecular
      entity approval.

PMID- 30222424
TI  - Risk Minimization Activities and Measures of Effectiveness: A New Approach.

PMID- 30222425
TI  - A Method of Addressing Proprietary Name Similarity for US Prescription Drugs.
AB  - There is an increased risk of medication error and harm to a patient whenever 2
      or more drug product names appear alike in sound, look, or meaning. Any ambiguity
      of the proprietary name ("trade" or "brand" name) of a drug product can lead to
      errors in ordering, dispensing, or administering medication. A drug's name is a
      critical identifier, and correct product identification is important to the
      responsible administration of medicine. This article describes a series of tools
      created for regulatory reviewers to enhance the review of proprietary names under
      current federal regulations, with the goal of encouraging further innovation
      toward the goal of medication safety. These tools include measures of
      orthographic, phonetic, and semantic similarities and are designed be used
      together with the existing computerized measures of similarity. It is the hope
      that highlighting the importance of medication error reporting for the safety
      review process will further encourage health care professionals to provide
      adequate and detailed reporting regarding medication errors, which will lead to
      improvements in the overall safety review process.

PMID- 30222426
TI  - An Evaluation of the Efficiency of the Gulf Cooperation Council's Centralized
      Procedure by the Gulf Regulatory Authorities and Pharmaceutical Companies:
      Recommendations for an Improved Model.
AB  - The aim of this study was to examine the views and experiences of the Gulf
      Cooperation Council (GCC) states and pharmaceutical companies to identify the
      strengths and weaknesses of the GCC centralized registration procedure (GCC-CP).
      Results of a questionnaire designed for the study and completed by GCC regulatory
      authorities and pharmaceutical companies who registered products through the GCC
      CP showed that it is an effective system. However, it demonstrated that there is
      room for improvement. For example, provision of clear guidelines, transparency of
      procedures, effective interactions between authorities and companies, an increase
      in the number of committee meetings, and the use of electronic online submissions
      would shorten approval times and enhance the quality of review practice as well
      as encourage pharmaceutical companies to use the GCC-CP system. This research
      enabled the development of an improved model of the GCC-CP to be proposed to the
      GCC Health Authorities, which could expedite patients' access to medicines in the
      region.

PMID- 30222427
TI  - Current Trends in Personalized Medicine and Companion Diagnostics: A Summary From
      the DIA Meeting on Personalized Medicine and Companion Diagnostics.
AB  - Personalized medicine has reached the mainstream, accounting for more new drug
      approvals and a promising pipeline of candidate therapeutics. Recent advances in
      genomics, computational biology, medical imaging, diagnostic technologies, and
      translational medicine are creating the possibility for scientists to develop
      diagnostic tools and new treatments for cancer, genetic disorders, and infectious
      diseases that may be particularly effective in biomarker-defined subpopulations.
      Drug development under this model creates new challenges that will require the
      need for increased regulatory flexibility, novel clinical trial designs, and
      translational science development. In this review, the authors highlight key
      developmental and regulatory challenges in the advancement of personalized
      medicines and their associated companion diagnostics with the need for innovative
      clinical trial designs to support drug/diagnostic development and registration.
      Further, the clinical complexities of implementing new technologies are
      considered, such as high-throughput next-generation sequencing in personalized
      medicine, and offer a glimpse of the regulatory and policy considerations shaping
      this methodology in multimarker diagnostic development.

PMID- 30222428
TI  - APEC Workshop Report of Good Review Practices on Medical Products.
AB  - As part of the implementation of the 2020 Good Review Practices (GRevP) Roadmap
      championed by Chinese Taipei in the Asia-Pacific Economic Cooperation (APEC)
      Regulatory Harmonization Steering Committee (RHSC), the Taiwan Food and Drug
      Administration (TFDA) organized 2 workshops. The purpose of these workshops was
      to address the fundamental elements of a well-designed regulatory review system,
      to provide complementary modules for GRevP and approaches to the exchange and the
      use of product assessment reports between regulatory authorities, and to further
      promote regulatory efficiencies and best practices. The workshops brought
      together 81 regulatory representatives from 15 economies for the basic workshop
      and 133 from 20 economies for the advanced workshop. Participants forged a common
      understanding of GRevP and highlighted its importance. While the adoption of
      GRevP is key to building trust between agencies, each economy should address its
      needs and adopt its own best practices based on its resources and environment.
      The outcomes of these workshops could be used as a framework for the development
      of a GRevP best-practice document or could serve as material for further training
      in each economy.

PMID- 30222429
TI  - Statistical Challenges in the Analyses of Bone Mineral Density in Pediatric
      Populations.
AB  - Assessing bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is
      standard in clinical practice with good precision and reproducibility. One way to
      analyze BMD data is through the Z-score where a subject's BMD is standardized
      against some reference population. This article highlights several potential
      problems in the calculation of the Z-score: (1) reference data are manufacturer
      dependent; (2) a transformation is recommended to reduce the skewness often seen
      in BMD data, however a transformation parameter is only available in some
      references using the Hologic manufacturer; (3) some reference data may be
      obsolete, as they were done under older scan models; (4) reference data are
      recommended to be interpolated to the subject's age, and linear interpolation is
      questionable; (5) reference data do not exist for all age groups; (6) reference
      data depend on the race of the subjects, and not all races are representative;
      and (7) reference data are limited to certain body composition. Given the
      limitation in the BMD Z-scores, other clinical symptoms (eg, bone fractures) or
      laboratory findings (eg, bone biomarkers) should be assessed in conjunction with
      the BMD Z-score to evaluate a subject's bone health.

PMID- 30222430
TI  - Monitoring and Evaluating the Effect of Regulatory Action: Some Recent Case
      Studies.
AB  - Large electronic health care databases can be used to evaluate the effectiveness
      of regulatory action. Designing and interpreting such studies can be challenging.
      We demonstrate using case studies on modafinil, benzodiazepines, dosulepin, and
      piroxicam that measuring the impact of regulatory action is possible and can be
      beneficial, particularly in determining the need for further action or
      communication. For each case study, we discuss difficulties that may arise when
      measuring the effectiveness of regulatory action, which include but are not
      limited to: the choice of denominator, changes in the patient population, the
      availability and selection of comparators, and the fact that the regulatory voice
      may be but one voice among many. The evaluation of regulatory action is possible,
      but not without its challenges, and a routine, one-size-fits all approach is
      unlikely to be possible.

PMID- 30222431
TI  - Multifaceted Paths Toward Advancing Regulatory Science.

PMID- 30222432
TI  - Comparison of Approved Dosages for Pediatric and Adult Populations Based on US
      Labeling Information.
AB  - BACKGROUND: The passing of legislation in the United States and the European
      Union has led to the approval of dosages for pediatric use. This study was
      conducted in an attempt to find potentially important factors with regard to dose
      selection for the pediatric population. METHODS: The FDA's New Pediatric Labeling
      Information Database was used for this study. Drug labels for patients aged 6
      months as well as those for patients aged 2, 6, and 11 years were standardized
      based on dosages expressed by age, normalized body weight (BW), and body surface
      area (BSA) in order to obtain ratios of pediatric-to-adult dosages. Labeling for
      108 drugs were extracted for the analysis. RESULTS: Ratios of pediatric-to-adult
      dosages based on BW were higher than 1, but those based on BSA were around 1.
      Relative dosages at 6 months of age showed a stronger correlation with those at 2
      years compared to those at other ages. CONCLUSION: The approved dosages for
      pediatrics based on BW were higher than those of adults, but the ones based on
      BSA were almost the same as those of adults. The closer the age groups, the
      stronger the correlation of relative dosages between the groups.

PMID- 30222433
TI  - What Defines Good Quality in a Clinical Study Report?
AB  - Although clinical study reports (CSRs) are one of the central documents in
      clinical development, little attention has been paid to those features of such
      reports that determine their overall quality. While the ICH E3 guideline mentions
      a few quality attributes for CSRs, there are hardly any publications concerned
      with determining the key quality features of CSRs. This aspect is also often
      missing in medical writing textbooks. This study set out to identify the elements
      that contribute to the overall quality of clinical study reports using guided
      interactive introspection in a medical writing group (N = 28). All medical
      writers had a science background with a PhD; their professional experience ranged
      from 1 to 17 years (mean: 3.3 years). In total, 16 quality items were determined,
      which were grouped into 5 major areas: language, document structure, numerical
      information, audience focus, and company context. Ordered by decreasing
      importance, the 10 most important elements were: correctness, completeness,
      regulatory compliance, clarity of structure, conciseness, consistency,
      timeliness, appropriate language and style, adequate conclusion, and alignment
      with clinical project. The quality of clinical trial reports proved to be
      multifactorial and multidimensional; the overall quality cannot be represented by
      any single quality item. To achieve optimal quality, medical writers need to
      apply professional judgment to balance between those elements that were
      identified as contributing to overall document quality.

PMID- 30222434
TI  - Assessment of the e-Answers Initiative, a New Model for Response by Email to
      Scientific Information Requests Carried Out by the Medical Information Service of
      Novartis Pharmaceuticals in Spain: Results of an Internal Satisfaction Survey.
AB  - BACKGROUND: The aim of this study was to evaluate internal customer satisfaction
      with the Medical Information Service of Novartis Farmaceutica after changing to a
      new model of response by email to scientific information requests (the e-Answers
      initiative). METHODS: A survey, conducted 3 months after the e-Answers initiative
      was implemented, was designed to determine the profile of each respondent and
      included 10 multiple-choice questions on user satisfaction. A 7-point Likert-type
      scale was used whenever possible. RESULTS: A total of 97 responses (50.5%) were
      analyzed. Overall satisfaction with the change was favorable for 94% of
      respondents, and 94% and 97% of respondents evaluated favorably the elimination
      of paper load and the decrease in environmental impact, respectively.
      Satisfaction with response time since implementing the new model was positive for
      91% of the respondents. CONCLUSION: In this anonymous survey with high
      participation of service users, the e-Answers initiative was evaluated
      positively.

PMID- 30222435
TI  - An Analysis of the Fixed-Dose Combinations Authorized by the European Union, 2009
      2014: A Focus on Benefit-Risk and Clinical Development Conditions.
AB  - BACKGROUND: Apparent issues with the treatment and management of complex,
      chronic, and multifactorial diseases with monotherapies are becoming more
      prevalent, with a potential solution being fixed-dose combinations (FDCs). There
      is a certain stigma associated with FDCs, namely after the bans in the mid- to
      late 20th century; however, FDCs have proven useful in improving efficacy,
      reducing adverse effects, prolonging marketability, and producing new therapeutic
      entities. In addition to this, FDCs may be advantageous in increasing patient
      compliance and reducing off-label use. METHODS: FDCs authorized by the European
      Union in the past 5 years were analyzed according to benefit-risk and clinical
      trial design. RESULTS: An overall stable authorization of FDCs from 2009 to 2014
      was observed, with most being developed to treat cardiac- and immune-related
      disorders.The aforementioned bans have led to stricter guidelines and regulations
      on FDCs; however, the examples presented demonstrate that the clinical guidelines
      from the European Medicines Agency are flexible within limits and may be altered
      given proper justification. CONCLUSION: With off-label use, profitability, and
      reimbursement threatening the development of FDCs, it is the patients who end up
      suffering the most. The industry, regulatory bodies, and patients need to unite
      for the successful development of new FDCs.

PMID- 30222436
TI  - How the Critical Path Initiative Addresses CDER's Regulatory Science Needs: Some
      Illustrative Examples.
AB  - Since 2008, the Critical Path Initiative has supported FDA's program of
      intramural research projects in regulatory science, with the goal of improving
      translation of advances in emerging sciences to the development of safe and
      effective medical products. Since 2011, the research of FDA's Center for Drug
      Evaluation and Research (CDER), including the work supported by the Critical Path
      Initiative, has been guided by the regulatory science needs identified in the
      CDER science and research needs report. In this review, the authors highlight a
      few of CDER'S Critical Path Initiative research projects, each addressing a
      different regulatory science need, to illustrate the diversity of regulatory
      science at CDER. They also describe elements common to these research projects,
      including broad collaboration with external partners, an increasing dependence on
      large data sets and computational models, and requirements for resources or
      perspectives specific to FDA.

PMID- 30222438
TI  - Choosing Appropriate Estimands in Clinical Trials (Leuchs et al): Letter to the
      Editor.

PMID- 30222437
TI  - Communicating Benefit and Risk Information in Direct-to-Consumer Print
      Advertisements: A Randomized Study.
AB  - BACKGROUND: Previous research demonstrated that providing qualitative and
      quantitative information in a "drug facts box" may help individuals understand
      prescription drug information in print-based direct-to-consumer advertisements.
      The authors sought to determine whether qualitative, quantitative, or a
      combination thereof best communicates benefit and risk information. METHODS: To
      replicate and extend previous research, the authors used simple quantitative drug
      information. A randomized controlled study was conducted with 5067 Internet
      panelists with heartburn. Participants viewed a drug facts box with benefit and
      risk information that varied the presence or absence of qualitative summaries and
      absolute frequencies, percentages, and absolute differences. Measures included
      knowledge of drug benefits and risks, perceptions, and intentions. RESULTS:
      Providing absolute frequencies and percentages most improved participants' drug
      knowledge and affected perceptions and intentions. CONCLUSIONS: The study
      findings suggest that, for simple drug information, adding absolute frequencies
      and percentages to direct-to-consumer advertisements may benefit consumers.
      Absolute differences and qualitative labels may not be needed.

PMID- 30222439
TI  - Cardiac Safety Research Consortium (CSRC): Cardiovascular Safety and Adverse
      Event Case Report Forms.
AB  - Detection of off-target cardiovascular (CV) effects remains a significant
      challenge to drug development. Documentation of CV events in non-CV trials is
      often inadequate to interpret imbalances between treatment arms, which may lead
      to concerns about potential CV safety "signals." The Cardiac Safety Research
      Consortium (CSRC) public-private partnership has developed CV case report forms
      (CRFs) for adverse CV events, including death. These CRFs are intended to
      encourage collection, as near to the occurrence of an event as possible, of the
      minimum information necessary to assess, or possibly adjudicate, the event. A
      broad range of stakeholders (representing industry, academia, and regulatory
      authorities) developed these forms with the goal of balancing the collection of
      key information with the resources likely to be available. Use of these forms is
      optional, and sponsors may modify them. These forms have not undergone any type
      of "validation" process. The CSRC will continue to sponsor a working group to
      invite public comment and feedback on these forms.

PMID- 30222440
TI  - Choosing Appropriate Estimands in Clinical Trials.
AB  - Lack of adherence to study protocol and missing data are often unavoidable in
      clinical trials, and both increase the need to differentiate between the ideal
      treatment effect if the medication is taken as directed and the treatment effect
      in presence of the actual adherence pattern. In this regard, estimands have
      become the focus of attention. An estimand is simply that which is being
      estimated. In the context of treatment benefit, an estimand may address either
      efficacy or effectiveness aspects. Defining the estimand of interest is an
      essential step to take before deciding on trial design and primary analysis. The
      choice of estimand has consequences for various other factors to be considered
      during any clinical trial's planning phase. This study presents a process chart
      including all aspects to consider during planning. After deciding on the primary
      estimand, the trial design should be specified, followed by the primary analysis.
      Both should appropriately address the chosen estimand. Finally, sensitivity
      analyses should be taken into account. Provided are suggestions for all the
      planning steps involved, especially on choosing between efficacy and
      effectiveness, and relevant examples from clinical practice to illustrate them.
      It is recommended that one bear in mind the process chart during planning of any
      clinical trial and give reasonable justification for each decision in the study
      protocol.

PMID- 30222441
TI  - Drug Safety and the Cost of Monitoring: The Role of REMS in Risk Management.
AB  - BACKGROUND: The mission of the US Food and Drug Administration (FDA) can be
      viewed as a pendulum that swings between protecting public health and patient
      safety and promoting the public health through the drug review and approval
      process. Two decades of legislation have by and large provided the FDA with
      additional resources under the successive reauthorizations of the Prescription
      Drug User Fee Acts (PDUFA) to provide a necessary infusion of funds to hire
      medical experts, scientists, and epidemiologists, among other disciplines, to
      expedite review of new drug and biologic applications. However, a renewed
      attention to potential adverse drug experiences, culminating in the Vioxx
      withdrawal, has resulted in the passage of the Food and Drug Administration
      Amendments Act of 2007 (FDAAA). Under this act, the FDA was authorized to impose
      postapproval requirements on the biopharmaceutical industry through the
      imposition of risk evaluation and mitigation strategies (REMS) and postmarketing
      trial (PMT) requirements to improve drug safety. Despite the extensive dialogue
      between stakeholders and lawmakers in the development of the FDAAA, there remains
      some uncertainty as to the exact impact of REMS on not only operational costs for
      both industry and health care professionals but also product sales and
      prescribing habits in the 5 years since its implementation. METHODS: Recognizing
      that in the past 2 years, the use of REMS has shifted markedly, we sought to
      provide greater clarity on the duration of REMS requirements and impact of REMS
      on drug sales. RESULTS: While in absolute terms, the use of REMS may be
      declining, the REMS experience has provided an important, perhaps even critical,
      step in the development of current risk management strategies aimed at improving
      patient safety.

PMID- 30222442
TI  - Sample Size and the Precision of the Confidence Interval in Meta-analyses.
AB  - Sample sizes affect the precision of the confidence interval for the common
      effect size in a meta-analysis, which includes a number of independent studies of
      varying sizes. This paper provides a simplified method to estimate the precision
      of the confidence interval for the common effect size by using the number of
      independent studies and the average sample size of the independent studies. The
      simplified method proves to be very accurate for the retrospective meta-analyses.
      Two examples are then given to show how an investigator can use the number of
      independent studies and the average sample size of the individual studies to
      assess the precision of the confidence interval in a prospective meta-analysis.

PMID- 30222444
TI  - 2015 and Beyond.

PMID- 30222443
TI  - A Descriptive Evaluation of Prescriber Perceptions and Experience With Risk
      Evaluation and Mitigation Strategy (REMS) Programs in an Integrated Health Care
      System.
AB  - OBJECTIVE: To assess prescriber perceptions and experience with risk evaluation
      and mitigation strategy (REMS) programs in an integrated health care delivery
      system. METHODS: A cross-sectional online survey was e-mailed to eligible health
      care prescribers if they prescribed at least 1 selected REMS-related product
      within 6 months spanning January 1 to June 30, 2013; were an active employee of
      Kaiser Permanente Southern California; and had an active " kp.org " e-mail
      address. Descriptive analyses were conducted on the survey responses. RESULTS:
      Three hundred sixty-four respondents (34%) completed the online survey. The
      majority were primary care prescribers (65%) versus nonprimary prescribers. The
      majority of primary care, oncologist, and specialist prescribers responded that
      REMS was meaningful, improved patient safety, and made an impact on their patient
      interactions. The majority of surgeons and pain management prescribers responded
      that REMS was not meaningful, did not improve safety for the patients, or did not
      impact their interactions with their patients. Over 50% of prescribers counseled
      their patients or had another health care team member discuss the risks and
      benefits of these REMS-related medications; medication guides or other printed
      literature was not provided as much. CONCLUSION: The results from the survey
      suggest that prescriber specialty has an impact on the perceived value of the
      REMS program and the perceived need to counsel patients regarding medications
      with REMS programs.

PMID- 30222445
TI  - Effective Drug Supply for Adaptive Clinical Trials: Recommendations by the DIA
      Adaptive Design Scientific Working Group Drug Supply Subteam.
AB  - During the past decade, there has been increasing interest in adaptive clinical
      trials in pharmaceutical drug development as a means to improved decision making,
      better dose selection, and reduction in cost and time to market. Nevertheless,
      the operational challenge of drug supply continues to be a barrier preventing
      greater uptake of adaptive designs. Such studies require the ability to quickly
      accommodate changes in treatment allocation while maintaining the integrity of
      the blind. The DIA Adaptive Design Scientific Working Group formed a subteam to
      discuss solutions to the drug supply dilemma. In this paper, the subteam
      discusses effective strategies for drug manufacturing, labeling, packaging, and
      randomization and addresses financial concerns.

PMID- 30222446
TI  - Reduction in Medication Errors: The Fentora Case Study.
AB  - Fentora (fentanyl citrate) is an analgesic opioid used in the management of
      breakthrough pain in adult cancer patients. Numerous reports of medication errors
      had been reported since the product's launch in 2006, 74% of which were
      prescribing errors. Subsequent to the initiation of a risk evaluation and
      mitigation strategy (REMS) by FDA and the sponsor in 2011, reports of prescribing
      errors dropped rapidly. It is likely the REMS had a significant impact on the
      safe use of this important product. While further data from subsequent years
      would be needed to confirm this hypothesis, this is one of the first reports of
      an FDA and industry cooperative effort that showed a rapid increase in the safe
      use of a marketed pharmaceutical product as result of a REMS program.

PMID- 30222447
TI  - Management of Clinical Trial Agreements: Current Practices of Investigators in
      the United States.
AB  - The clinical trial agreement (CTA) is a key but often underappreciated document
      governing the relationship between a study site and a sponsor. Previous anecdotal
      materials have suggested that investigators may not often be involved in the
      review or negotiation of the CTA and may attach little importance to it. To
      provide more systematic current information, survey methods were used to explore
      the level of engagement, knowledge, and perceptions of investigators in the
      United States. The survey was distributed to more than 700 investigators
      university affiliated and nonaffiliated-and/or related study staff, of whom 167
      responded. Most respondents identified that they did not manage the clinical
      trial agreement process but were actively engaged in its review. Most were
      encouraged by their institutions to participate. However, some respondents
      expressed concerns with regard to their satisfaction with the content of the CTA,
      particularly with respect to issues such as financial negotiations and payments,
      indemnification, and subject injury language. The majority of investigators
      either strongly agreed or agreed that it was important for the investigator to be
      actively involved in the CTA process. Data from this survey provide the first
      systematic look at the current practices of US investigators, possible issues,
      and areas for improvement from the investigator's point of view.

PMID- 30222448
TI  - Valacyclovir-Induced Acute Kidney Injury in Japanese Patients Based on the PMDA
      Adverse Drug Reactions Reporting Database.
AB  - BACKGROUND: More than 250,000 reports of adverse drug events were included in the
      database of the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan.
      However, these data have not been utilized sufficiently for analysis. While
      valacyclovir is the antiviral agent used worldwide, it is reported to induce
      nephrotoxicity. The aim of this study was to clarify the profiles of valacyclovir
      induced adverse events using the PMDA database. METHODS: Case reports were
      screened in the PMDA adverse event database from 2004 to 2011. The profiles of
      patients with acute kidney injury (AKI) were analyzed by sex, age, diseases,
      concomitant suspected drugs, and outcomes. RESULTS: A total of 514 kidney-related
      adverse events were detected, and 344 were cases that included AKI. Of the AKI
      cases, 246 patients (71.5%) were female. There were 145 patients who were 70 to
      79 years of age, which was the most affected of all age groups. Of the 344
      patients, 183 patients had hypertension, and 65 had diabetes. Valacyclovir was
      the only drug used among 257 patients (74.1%). CONCLUSIONS: There were many
      reports of AKI involving valacyclovir and females, particularly in the 70- to 79
      year age group in Japan. The results suggest that these patients were most likely
      to develop AKI after valacyclovir treatment.

PMID- 30222449
TI  - Incorporating Historical Data in Bayesian Phase I Trial Design: The Caucasian-to
      Asian Toxicity Tolerability Problem.
AB  - Following phase I dose-finding oncology trials completed in Western countries,
      Asian investigators often conduct further phase I trials to determine the maximum
      tolerated dose for Asian patients. This may be due to concerns about possible
      differences in treatment tolerability between Caucasian and Asian patient groups.
      Our proposed approach aims to appropriately borrow strength from a previous
      Caucasian trial to improve the maximum tolerated dose determination in an Asian
      population of patients. We design an Asian phase I trial using the Bayesian
      continual reassessment method. First we analyze toxicity data from a Caucasian
      trial to derive the prior distributions for a subsequent Asian trial. Then, we
      calibrate the informativeness of the prior distributions according to prior
      effective sample size defined by Morita et al. Extensive simulation studies
      demonstrate favourable operating characteristics of the proposed method, compared
      with two methods based on power and noninformative priors, respectively.

PMID- 30222450
TI  - A Universal Framework for the Benefit-Risk Assessment of Medicines: Is This the
      Way Forward?
AB  - A universal framework for the evaluation of the benefit-risk assessment of
      medicines during development by pharmaceutical companies and in the regulatory
      review by regulatory authorities is considered of value, as it would result in
      the systematic structured approach to support transparency in decision making.
      Several organizations have developed frameworks over the past few years,
      including those recommended by pharmaceutical companies such as the PhRMA BRAT
      (Pharmaceutical Research and Manufacturers of America Benefit-Risk Action Team)
      and the BRAIN (Benefit-Risk Assessment in New and Old Drugs) as well as
      frameworks advanced by regulatory agencies, including the FDA 5-step framework
      and the EMA PrOACT-URL. However, a review of the criteria-including logical
      soundness, comprehensiveness, acceptability of results, practicality, specificity
      and sensitivity, presentation (visualization), and scope proposed for the
      development of a universal framework-demonstrated that all these different
      frameworks described can be incorporated into UMBRA (Universal Methodology for
      Benefit-Risk Assessment).

PMID- 30222451
TI  - The Wider Use of Fixed-Dose Combinations Emphasizes the Need for a Global
      Approach to Regulatory Guideline Development.
AB  - A fixed-dose combination (FDC) is a drug product in which two or more separate
      drug components (active pharmaceutical ingredients) are combined in a single
      dosage form. Interest in developing FDCs is increasing in a range of diseases.
      This project investigated the regulatory environment for FDCs in the EU and US. A
      review of the FDC guidelines set forth by the EMA, FDA, and ICH, followed by
      interviews of key informants in industry, identified 5 main industry concerns
      related to development of FDCs. These concerns were presented to key informants
      from both the EU and US regulatory authorities. It was clear from the results
      that the current regulatory environment for FDCs lacks consistency. This may
      create a barrier to innovation moving from the laboratory to the clinic, as
      companies cannot clearly see the development path requirements. This project also
      highlighted certain challenges that currently face the regulatory world: how to
      improve the role of regulatory science and provide clear quantification in
      assessment decisions; the role of guidelines and their impact on innovation; and,
      most important, the question of globalization and how to move toward a more
      harmonized regulatory system.

PMID- 30222452
TI  - Clinical Development Approaches and Statistical Methodologies to Prospectively
      Assess the Cardiovascular Risk of New Antidiabetic Therapies for Type 2 Diabetes.
AB  - In December 2008, the US Food and Drug Administration (FDA) issued a guidance for
      industry requiring sponsors to demonstrate that a new antidiabetic therapy being
      developed to treat type 2 diabetes does not increase cardiovascular (CV) risk to
      an unacceptable extent. CV events reported during phase 2 and phase 3 trials
      should be prospectively and independently adjudicated. Before submission of a new
      drug application or biologics license application, sponsors should compare the
      incidence of major CV events occurring with the investigational agent versus the
      control group to show that the upper bound of the 2-sided 95% confidence interval
      (CI) for the estimated risk ratio is less than 1.8. If the CI includes 1.3, a
      postmarketing trial will be necessary to definitively show that the upper bound
      of the 95% CI for the estimated risk ratio is then less than 1.3. In 2012, the
      European Medicines Agency (EMA) issued an updated guideline on the clinical
      investigation of medicinal products in the treatment or prevention of diabetes
      mellitus that detailed its CV safety assessment requirements. Although similar to
      the FDA guidance, the EMA guideline does not prospectively define any pre- or
      postapproval risk margins. This expert perspective, prepared by members of the
      Cardiac Safety Research Consortium, discusses clinical development strategies,
      operational issues, and statistical methodological issues to satisfy the FDA's CV
      safety requirements, and, where appropriate, the EMA guideline. Actual case
      examples, where applicable, are presented.

PMID- 30222453
TI  - The Patient-Reported Outcome (PRO) Consortium: Lessons Learned Along the Path to
      PRO Instrument Qualification.
AB  - Established in 2008, the Patient-Reported Outcome (PRO) Consortium is a
      collaboration among the US Food and Drug Administration's Center for Drug
      Evaluation and Research, the Critical Path Institute, the
      pharmaceutical/biotechnology industry, and other stakeholders. The purpose of the
      consortium is to qualify PRO instruments through the Center for Drug Evaluation
      and Research's drug development tool qualification process for use as clinical
      trial endpoints to support drug approval and product labeling claims. The PRO
      Consortium has made notable progress toward collaborative development of PRO
      instruments in the following areas: asthma, mild cognitive impairment,
      depression, functional dyspepsia, irritable bowel syndrome, non-small cell lung
      cancer, and rheumatoid arthritis. This progress has come with considerable
      challenges, including navigating a new and evolving regulatory initiative,
      gaining consensus on key issues, and maintaining communication and engagement in
      a precompetitive environment. The purpose of this paper is to describe some of
      the challenges and lessons learned since the creation of the PRO Consortium in
      hopes that this information may provide direction and insight for similar
      collaborations.

PMID- 30222454
TI  - Patient Engagement by Pharma-Why and How? A Framework for Compliant Patient
      Engagement.
AB  - Engagement is increasingly recognized as a decisive factor for health-related
      outcomes in people living with a medical issue. It is their experience that
      drives this engagement. Therefore, providers who seek to develop better
      solutions, including medicines, must gain a deeper understanding of the patient
      experience. Beyond pathology, such understanding requires direct engagement with
      patients, something that has been historically avoided in the pharmaceutical
      industry. Whereas clear and comprehensive engagement frameworks are in place for
      direct engagement with health care professionals, such guidance does not yet
      exist for engagement with patients. A patient engagement framework has been
      developed at UCB to fill this gap, and it is herewith shared publicly as a
      contribution to setting and raising standards in patient engagement, with the
      ultimate aim of fostering the development of better solutions for people living
      with medical issues.

PMID- 30222455
TI  - Inferences Beyond a Study Design's Grasp: A Cautionary Case Study From the Recent
      Renal Sympathetic Denervation Literature.
AB  - During the past 6 years, the technique of renal sympathetic denervation has been
      proposed as a treatment for drug-resistant hypertension, and several studies have
      been published that claimed to provide supportive evidence of its efficacy. There
      is no question that resistant hypertension is a major medical concern:
      hypertension has been authoritatively designated as the greatest threat to the
      global burden of disease, and approximately 8% of hypertensive individuals have
      resistant hypertension. However, the first studies reporting the efficacy of
      renal sympathetic denervation were not methodologically capable of supporting
      such claims. Subsequently, in March 2014, the most appropriately designed
      clinical trial failed to provide supportive evidence of the intervention's
      efficacy. This Commentary presents a cautionary case study to exemplify the need
      for optimal methodologic rigor in all experimental clinical research and
      highlights the pitfalls should claims from less than optimally rigorous studies
      be afforded more weight than is scientifically appropriate.

PMID- 30222456
TI  - Multivariate Common Language Effect Size.
AB  - To find a common language effect size of multivariate outcomes, we convert the
      standardized multivariate effect size (Mahalanobis distance) to a probability of
      a randomly selected subject from one population having a larger discriminant
      function than a randomly selected subject from another population. This
      probability is simple to calculate and comprehensible to laypeople. It can serve
      as the multivariate common language effect size to compare not only two groups
      but also more than two groups.

PMID- 30222457
TI  - A Survey of Key Opinion Leaders to Support Curriculum Development in Advanced
      Medical Science Liaison Training.
AB  - Medical science liaisons (MSLs) are field-based pharmaceutical or biomedical
      industry professionals whose role demands specialized product knowledge and skill
      in executing customer-facing activities. This report describes a survey of key
      opinion leaders (KOLs) to identify MSL skills most highly valued and those in
      need of enrichment with the objective of designing an advanced training
      curriculum for experienced MSLs. A total of 66 MSLs representing diverse
      therapeutic areas verbally administered a 9-question survey at the conclusion of
      a routine MSL-KOL interaction. There were 296 surveys completed, with most
      respondents (239 of 281; 82%) indicating that they meet with MSLs from other
      companies. Ninety-five percent (218 of 230) responded that the value provided by
      MSLs was comparable to that offered by other companies. When asked about top MSL
      attributes, KOLs mentioned product knowledge, scientific credibility, therapeutic
      area knowledge, timeliness of response, and communication skills. In terms of
      resources provided by MSLs, KOLs most often mentioned scientific information,
      unbiased product information, therapeutic area developments (including pipeline
      discussions), disease state information, and potential involvement in research or
      as an advisor. Based on the quantitative and qualitative results of this survey,
      a workshop curriculum focusing on advanced communication skills and networking
      techniques was developed and conducted successfully.

PMID- 30222458
TI  - Exact Bayesian Inference Comparing Binomial Proportions, With Application to
      Proof-of-Concept Clinical Trials.
AB  - The authors revisit the problem of exact Bayesian inference comparing two
      independent binomial proportions. Numerical integration in R is used to compute
      exact posterior distribution functions, probability densities, and quantiles of
      the risk difference, relative risk, and odds ratio. An application of the
      methodology is given in the context of randomized comparative proof-of-concept
      clinical trials that are driven by evaluation of quantitative criteria combining
      statistical significance and clinical relevance. A two-stage adaptive design
      based on predictive probability of success is proposed and its operating
      characteristics are studied via Monte Carlo simulation. The authors conclude that
      exact Bayesian methods provide an elegant and efficient way to facilitate design
      and analysis of proof-of-concept studies.

PMID- 30222459
TI  - Development and Use of Reprints Tracking Reporter (RTR(c)) as a Medical
      Information Web-Based Tool for Compliance with the Physician Payments Sunshine
      Act.
AB  - Dissemination of full-article references in connection with medical information
      responses from pharmaceutical industry medical information departments (PIMID)
      has both copyright and Physician Payments Sunshine Act (PPSA) compliance
      requirements. A complex of data must be aggregated from multiple databases, which
      presents a challenge in efficiently distributing articles and reporting the
      metrics. Using contemporary programming methods that any PIMID can duplicate and
      that is described herein, the authors developed a web-based tool (Reprints
      Tracking Reporter [RTR(c)]) to meet this need. Information is compiled from an
      inquiry management database (IRMS(r)) and library bibliographic database
      (Quosa(r)) and matched to the physician National Provider Identifier number per
      the National Plan and Provider Enumeration System database. RTR identified 2179
      unique references from all of the response letters and then matched their
      copyright status. Several report formats allow for tracking distribution by
      article, customer, or state and generating Item/Transfer of Value aggregate spend
      reports on a periodic basis. A notable trend has been decreased article requests
      from physicians after informing them of the PPSA reporting requirement.

PMID- 30222460
TI  - Smart Program Design Through a Common Information Model.
AB  - Although much information is already available publically from information
      sharing initiatives such as ClinicalTrials.gov, information about clinical
      programs is unstructured, inconsistent, and incomplete. Clinical research within
      bioscience companies, health care, academia, and governmental agencies could
      benefit from easier access to best practices, historical information, and
      improved information sharing. Facilitating information sharing requires a
      standardized information model. Information standards today focus on individual
      clinical trials and the representation of clinical trial data. Although work is
      ongoing to expand standards to cover the protocol, these are insufficient to
      capture the objectives, rationale, and design thinking behind clinical programs.
      An information model is proposed to cover the rationalization and decision-making
      aspects of designing a clinical program and its associated trials. This paper is
      the output of a newly formed multicompany working group that examines the merits
      of a clinical program-level information standard. An example information model is
      presented to explain the concept.

PMID- 30222461
TI  - Interprofessional Authorship in Critical Care Journals.
AB  - Interprofessional education and patient care have been endorsed by accrediting
      bodies because interprofessional health care teams improve outcomes while
      decreasing health care costs. Thus, there has been an increased focus in
      educating health professional students collectively. The purpose of this study
      was to investigate the frequency of interprofessional authorship of original
      research published in high-impact critical care journals. Physicians constituted
      76.2% of authors, followed by 10.5% PhDs and 3.0% nonphysician health
      professionals. From 2001 to 2011, the frequency of physician and nonphysician
      authors increased significantly ( P < .01 for both). Interprofessional authorship
      also increased, from 49.9% to 64.3% of published articles ( P < .0001). The
      enhanced attention on interprofessional education and patient care has translated
      into an increase in interprofessional authorship for original research articles
      published in critical care journals. However, collaboration appears to be
      primarily between physicians and PhDs, not other health care professionals.

PMID- 30222462
TI  - How Should a Globalized CTD Be Created? An Introduction to the Japanese 3-Layer
      Approach.
AB  - This article is based on the consensus of a task force of the Data Science Expert
      Committee, Japan Pharmaceutical Manufacturers Association. Common Technical
      Documents (CTDs) need to be harmonized in all of the ICH regions to enhance the
      scientific value and efficiency of these documents. Region-specific CTDs often
      require modifications for submission in different countries-an urgent issue not
      only for Japan but also for the countries where participation in the ICH
      framework will expand. CTDs themselves should be globalized, which means they
      should use not only a common format but also common contents, by incorporation of
      a 3-layer approach. In layer 1 of this approach, efficacy and safety of a study
      drug are evaluated through the overall study results; layer 2 entails evaluation
      of whether there is inconsistency in efficacy and/or safety of the study drug for
      a specific subgroup with overall results; and in layer 3, the results of layers 1
      and 2 are used to evaluate benefits and risks in each applying country. The 3
      layer approach can be used to create a globally common model using data collected
      in all countries in the study. This global evaluation allows benefits and risks
      to be evaluated in all countries and should allow globalized CTDs to be
      developed. Alignment between research and development sites by pharmaceutical
      companies and success of regulatory conventions can reduce the total amount of
      review time. Ultimately, these changes would lead to faster approval of new
      drugs.

PMID- 30222463
TI  - Funding of Cancer Research: Do Levels Match Incidence and Mortality Rates?
AB  - The incidence and mortality rates of the ten most prevalent cancers types in the
      US were compared with the National Cancer Institute's funding of clinical studies
      in 2012. Additionally, a sampling of print and broadcast media coverage of these
      ten cancer types were gathered for the same year. While funding per case and per
      annual death broadly matched cancer prevalence, significant exceptions existed.
      Breast cancer research is funded at the highest level on both a per-case and a
      per-death basis. Funding far exceeds that of any other cancer regardless of the
      measure examined. While second in prevalence in the US, actual dollars spent on
      breast cancer research in 2012 were more than double the dollars spent for the
      most prevalent cancer (prostate). Also, media mentions for breast cancers were
      nearly twice those for prostate cancers in 2012. Is the possible influence of
      public awareness, either by the media directly or through patient or specific
      cancer research advocacy groups, influencing the funding of cancer? Have we have
      reached a point where breast cancer is now overfunded by the National Cancer
      Institute relative to prostate cancer and other less publicly visible, yet
      nevertheless still deadly, cancers?

PMID- 30222464
TI  - An Assessment of Future Clinical Pharmacy Service Delivery in the Patient
      Centered Medical Home.
AB  - Two health care reform initiatives-patient-centered medical home (PCMH) and
      payment reform-in combination have the potential to increase clinical pharmacy
      involvement in patient care. However, the effects of these reforms on clinical
      pharmacy are highly uncertain. In particular, which clinical pharmacy services
      will be provided, how the services will be requested and delivered, and in what
      practice settings the services will be provided are not known. To gain insight
      into future clinical pharmacy service delivery in the PCMH, the authors examined
      current clinical pharmacy service delivery models at 4 sites in Massachusetts and
      assessed how the service delivery would change in PCMH settings with a payment
      approach of comprehensive payments to the PCMH. The findings suggest that (1)
      clinical pharmacy participation in the PCMH will increase at ambulatory care
      sites if supported by payment reform and (2) changes in addition to payment
      reform will be necessary to increase participation of community pharmacists.
      Needed changes are described.

PMID- 30222465
TI  - Methods and Issues to Consider for Detection of Safety Signals From Spontaneous
      Reporting Databases: A Report of the DIA Bayesian Safety Signal Detection Working
      Group.
AB  - Spontaneous reporting (SR) adverse event system databases, large observational
      databases, large clinical trials, and large health records databases comprise
      repositories of information that may be useful for early detection of potential
      harms associated with drugs, devices, and vaccines. All of the data sources
      include many different adverse events and many medical products, so that any
      approach designed to detect "important" signals of potential harm must have
      adequate specificity to protect against false alarms yet provide satisfactory
      sensitivity for detecting issues that really need further investigation.
      Algorithms for evaluating potential risks using information from these sources,
      especially SR databases, have been described in the literature. The algorithms
      may seek to identify potential product-event associations without any prior
      specifications, to identify events associated with a particular product or set of
      products, or to identify products associated with a particular event or set of
      events. This article provides recommendations for using information from
      postmarketing spontaneous adverse event reporting databases to provide insight
      into risks of potential harm expressed by safety signals and offers guidance
      regarding appropriate methods, both frequentist and Bayesian, to use in various
      situations as a function of the objective of the analysis.

PMID- 30222466
TI  - Bayesian Design of Proof-of-Concept Trials.
AB  - The proof-of-concept (PoC) decision is a key milestone in the clinical
      development of an experimental treatment. A decision is taken on whether the
      experimental treatment is further developed (GO), whether its development is
      stopped (NO-GO), or whether further information is needed to make a decision. The
      PoC decision is typically based on a PoC clinical trial in patients comparing the
      experimental treatment with a control treatment. It is important that the PoC
      trial be designed such that a GO/NO-GO decision can be made. The present work
      develops a generic, Bayesian framework for defining quantitative PoC criteria,
      against which the PoC trial results can be assessed. It is argued that PoC
      criteria based solely on significance testing versus the control are not
      appropriate in this decision context. A dual PoC criterion is proposed that
      includes assessment of superiority over the control and relevance of the effect
      size and hence better matches clinical decision making. The approach is
      illustrated for 2 PoC trials in cystic fibrosis and psoriasis.

PMID- 30222467
TI  - Characterization of Missing Data in Clinical Registry Studies.
AB  - Patterns of missing data are seldom well-characterized in observational research.
      This study examined the magnitude of, and factors associated with, missing data
      across multiple observational studies. Missingness was evaluated for demographic,
      clinical, and patient-reported outcome (PRO) data from a procedure registry
      (TOPS), a rare disease (cystic fibrosis) registry (Port-CF), and a comparative
      effectiveness registry (glaucoma, RiGOR). Generalized linear mixed effects models
      were fit to assess whether patient characteristics or follow-up methods predicted
      missingness. Data from 156,707 surgical procedures, 32,118 cystic fibrosis
      patients, and 2373 glaucoma patients were analyzed. Data were rarely missing for
      demographics, treatments, and outcomes. Missingness for clinical variables varied
      by registry and measure and depended on whether a variable was required. Within
      RiGOR, PRO forms were missing more often when collected by e-mail compared with
      office-based paper data collection. In Port-CF, missingness varied based on
      insurance status and sex. Strategic consideration of operational approaches
      affecting missing data should be performed prior to data collection and assessed
      periodically during study conduct.

PMID- 30222468
TI  - Analysis of the Current Situation of Antitumor Drug Use in China: A Hospital
      Based Perspective.
AB  - OBJECTIVE: To present a systematic review of the usage of antitumor drugs in
      Chinese hospitals from 2009 to 2011. METHODS: The market data of antitumor drugs
      was collected from the Menet database that covered 350 Class A tertiary hospitals
      from 16 major cities in China. The data of antitumor drugs were divided into 3
      categories by mechanism action: cytotoxic chemotherapy, molecular targeted
      therapeutic drugs, and other antitumor drugs. The usage characteristics of each
      category were analyzed through sales volume and sales value, and the
      characteristics of main drugs in each category were further analyzed. RESULTS:
      During 2009-2011, the sales volume and sales value of antitumor drugs used in
      hospitals had markedly increased in China. Specifically, cytotoxic chemotherapy
      was the most prevalent category in clinical treatment, with total sales volume
      shares of 61.93%, 63.90%, and 68.40% during 2009-2011. Its share of total sales
      value was more than 70% in the same period. The sales volume share of molecular
      targeted therapeutic drugs was less than 1%, but the sales value share was about
      20% in the corresponding period. In addition, plant alkaloids had become the
      leading subcategory of antitumor drugs in hospitals, which contributed 43.72% of
      total sales volume and 37% of total sales value in 2011. Antimetabolites still
      played an important role, with around 20% of sales volume, and monoclonal
      antibody and small-molecule compounds experienced rapid growth. CONCLUSIONS:
      Plant alkaloids have become the most widely used antitumor drug for clinical
      medical treatment in China. In the future, monoclonal antibody and small-molecule
      compounds are expected to have wider usage in China.

PMID- 30222470
TI  - On the front line: first choice pharmacotherapeutics for chronic lymphocytic
      leukemia.
AB  - INTRODUCTION: Chronic lymphocytic leukemia (CLL) is a common hematologic
      malignancy with a highly variable clinical course. Frontline treatments include
      cytotoxic chemotherapies, immunotherapies, and small molecule inhibitors.
      Clinical and molecular factors guide treatment initiation and selection. Over the
      last decade, refinement of CLL risk stratification tools and growth of the
      arsenal of effective therapeutics have profoundly improved outcomes. These
      advances have concurrently increased the complexity of managing the early phases
      of treatment. Areas covered: This review describes the factors considered in the
      determination of first-line treatment of CLL. Areas of emphasis include
      assessment of patient fitness, disease classification and risk stratification,
      and the mechanisms, efficacy, and toxicities associated with available
      pharmacotherapeutics. Expert opinion: Multiple different treatments may be
      appropriate for a specific clinical scenario, and selection among them requires
      discussion of relative risks and benefits. Advances in frontline CLL treatment
      will continue to shift the treatment paradigm toward prioritizing quality of life
      alongside survival, limiting treatment and toxicity, and the development of
      biologically rational synergistic drug combinations and sequences.

PMID- 30222469
TI  - The efficacy and safety of memantine for the treatment of Alzheimer's disease.
AB  - INTRODUCTION: Currently, five pharmacotherapeutic options are available to treat
      Alzheimer's disease: memantine; the three cholinesterase inhibitors donepezil,
      galantamine, and rivastigmine; and combination treatments with memantine and one
      cholinesterase inhibitor. Selection of the best course of treatment is based upon
      the evidence gathered by systematic reviews and meta-analyses of randomized
      controlled trials. Areas covered: This article provides a risk-benefit analysis
      of these treatments using evidence from meta-analyses on their safety and their
      efficacy. Expert opinion: Memantine improves cognitive functions and behavioral
      disturbances more efficiently than the placebo, both as monotherapy and in
      combination with donepezil. Although memantine monotherapy and combination
      therapy are associated with a few individual adverse events such as somnolence,
      it is well-tolerated and its safety (all-cause discontinuation) is comparable or
      superior to that of the placebo (agitation). Pooled cholinesterase inhibitors are
      superior to the placebo in the improvement of cognitive functions, but not
      behavioral disturbances and they are not well-tolerated, as evaluated by the high
      discontinuation rate. Donepezil (10 mg/day) and oral rivastigmine and galantamine
      monotherapies carry the risk for some adverse events including gastrointestinal
      symptoms. Therefore, we consider that combined treatment with memantine and
      donepezil is the most useful treatment for Alzheimer's disease.

PMID- 30222471
TI  - The efficacy of sapacitabine in treating patients with acute myeloid leukemia.
AB  - INTRODUCTION: Acute myeloid leukemia (AML) remains a poor prognosis hematological
      malignancy. The introduction of aggressive chemotherapy with allogeneic stem cell
      transplantation has resulted in improved clinical outcomes in younger patients.
      However, the treatment results in unfit elderly AML population remain
      disappointing. New strategies should be introduced to improve the prognosis in
      this group of patients. Areas covered: This review presents and discusses the
      mechanism of action, safety and efficacy of sapacitabine in AML patients. Expert
      opinion: Sapacitabine, a novel nucleoside analog, seemed to be a promising new
      agent for AML treatment. Its oral bioavailability and tolerable toxicity profile
      allow the drug to be used in an outpatient setting, especially in elderly unfit
      patients. Sapacitabine is known to have antileukemic activity in randomized
      clinical trials. In AML patients, sapacitabine monotherapy offered no advantage
      over low-intensity cytarabine treatment, and the combination of sapacitabine with
      decitabine was not significantly more effective than decitabine alone. However,
      the oral administration of sapacitabine allows it to be used in AML maintenance
      therapy.

PMID- 30222472
TI  - Differential Effect of Recurrent Concussions on Symptom Clusters in Sport
      Concussion Assessment Tool.
AB  - CONTEXT: Symptom checklist in Sport concussion assessment tool has been widely
      used in preseason assessment and in concussion diagnosis, but the impact of prior
      concussions on the graded symptoms after a new concussion has not been evaluated.
      OBJECTIVE: This study was undertaken to examine reported symptoms associated with
      recurrent concussions using data of a comprehensive survey among athletes.
      DESIGN: Retrospective survey and cross-sectional study. SETTING: Collegiate
      athletes. PARTICIPANTS: Student athletes who sustained one or more concussions.
      MAIN OUTCOME MEASURES: Concussion history and graded symptoms of the most recent
      concussion at time of the survey were surveyed. The impact of prior concussions
      was examined over symptoms and aggregated symptoms. RESULTS: Multiple concussions
      were associated with greater reporting of individual symptoms related to emotion
      and physical symptoms of sensitivity to light and noise: more emotional (z =2.3;
      p = 0.02), sadness (z = 2.4; p=0.02) , nervousness (z = 2.4; p=0.02),
      irritability (z = 3.6; p=0.01), sensitivity to light (z =2.6; p = 0.01), and to
      noise (z =2.4; p = 0.04),. The composite scores of emotional symptom and
      sensitivity symptom clusters were significantly higher: t = 2.68 (p < 0.01) and
      t= 3.35 (p< 0.01) respectively. CONCLUSIONS: The significant rises in emotional
      and sensitivity symptoms may be an important additive effect of concussive
      injury. Closer attention should be given to these symptom clusters when
      evaluating concussion injury and recovery.

PMID- 30222473
TI  - Marantic Endocarditis Associated With T-Cell Large Granular Lymphocytic Leukemia:
      First Report of Its Occurrence With a Lymphoproliferative Malignancy in Adults.

PMID- 30222474
TI  - Gathering Hints for Myofascial Force Transmission Under In Vivo Conditions: Are
      Remote Exercise Effects Age-Dependent?
AB  - CONTEXT: Recent research has underpinned the occurrence of non-local exercise
      effects. For instance, self-myofascial release (SMR) of the plantar fascia
      increases hamstring extensibility. A possible mechanism consists in a mechanical
      force transmission across myofascial chains. However, as the degree of structural
      continuity in these chains decreases with age, the magni-tude of the above
      described remote effects might also be reduced throughout lifespan. OBJECTIVE: To
      examine the age-dependency of non-local exercise effects following plantar fascia
      SMR. DESIGN: Regression experimental study. SETTING: General population.
      PARTICIPANTS: 168 healthy participants (45+/-21 years, 85 males). INTERVENTION:
      One 120 s bout of plantar foot SMR, performed in standing position. MAIN OUTCOMES
      MEASURE: Hamstring extensibility was assessed using sit and reach testing.
      Relative pre-post differences were classified as no im-provement, clinically non
      relevant improvement, or clinically relevant improvement according to previously
      published data. The age-dependency of the effects was calculated by means of
      multinomial stepwise logistic regression. If the latter revealed other factors
      than age to affect treatment effectivity, their effect was eliminated using
      partial correlation. RESULTS: SMR in-creased hamstring extensibility by 10.1%
      (pre: 24.9+/-9.7 cm, post: 27.4+/-9.3 cm, p<.0001). 99 participants (58.9 %)
      attained a clinically relevant change. Multinomial logistic regression
      demonstrated no influence of sex, amount of physical activity, height, BMI, and
      daytime, but a significant impact of baseline flexibility and age (Nagelkerke's
      r2=.32, p<.001). Post hoc partial correlation analysis demonstrated that age,
      corrected for baseline flexibility, had a small to moderate association with
      treatment effectivity (r=.29, p<.0001). CONCLUSIONS: Plantar foot SMR increases
      hamstring extensibility, which is explained by age to a small degree. Additional
      research is warranted in order to delineate the substrate of remote exercise
      effects. Besides mechanical force transmission, also cortical adaptations might
      represent the driving factor.

PMID- 30222475
TI  - Ankle Strength Deficits in a Cohort of Collegiate Athletes with Chronic Ankle
      Instability.
AB  - OBJECTIVES: Lateral ankle sprains commonly occur in an athletic population and
      can lead to chronic ankle instability (CAI). The objective of this study was to
      compare ankle strength measurements in athletes who have mechanical laxity and
      report functional instability after a history of unilateral ankle sprains.
      DESIGN: Retrospective cohort. SETTING: Athletic Training Research Lab.
      PARTICIPANTS: 165 National Collegiate Athletic Association Division I athletes,
      97 males and 68 females, with history of unilateral ankle sprains participated.
      MAIN OUTCOME MEASURES: Functional ankle instability (FAI) was determined by
      Cumberland Ankle Instability Tool (CAIT) scores and mechanical ankle instability
      (MAI) by the participant having both anterior (ANT) and inversion/eversion
      (INV/EV) laxity. Peak torque strength measures, concentric (CON) and eccentric
      (ECC), in two velocities were measured. RESULTS: Twenty-four subjects had both
      ANT and INV/EV laxity and 74 self-reported FAI on their injured ankle. The MAI
      group presented with significantly lower plantar flexion (PF) CON strength at 30
      degrees /sec (139.7+/-43.7 Nm) (p=.011) and EV CON strength at 120  degrees /sec
      (14.8+/-5.3 Nm) (p=.034) than the contralateral, uninjured ankle (166.3+/-56.8
      Nm, 17.4+/-6.2 Nm, respectively). CONCLUSION: Collegiate athletes who present
      with mechanical laxity on a previously injured ankle exhibit PF and EV strength
      deficits between ankles.

PMID- 30222476
TI  - Sex and Maturation Differences in Performance of Functional Jumping and Landing
      Deficits in Youth Athletes.
AB  - CONTEXT: Understanding how neuromuscular and biomechanical deficits that are
      associated with knee injuries change as youth mature may improve injury
      prevention strategies in this population. OBJECTIVE: To investigate sex and
      maturation differences in jump-landing technique performance in youths using a
      practical clinical tool. DESIGN: Cross-sectional study. SETTING: High Performance
      Center Laboratory. PARTICIPANTS: A total of 165 youth athletes were included in
      this study. MAIN OUTCOME MEASURES: The main outcome measures were each of the ten
      items of the modified Tuck Jump Assessment and the total score. These measures
      include knee valgus at landing (1), thighs do not reach parallel (2), thighs not
      equal side-to-side (3), foot placement not shoulder width apart (4), foot
      placement not parallel (5), foot contact timing not equal (6), excessive landing
      contact noise (7), pause between jumps (8), technique declines prior to ten
      seconds (9), and does not land in same footprint (10). RESULTS: Only knee valgus
      at landing had a significant sex*maturation interaction. The main effect of
      maturation was significant for items 2, 3, 6, 7, 9, and total score. Plyometric
      technique performance improved with increasing maturation. The main effect of sex
      was significant for items 1 and 9, with males performing better than females.
      CONCLUSION: Female athletes demonstrate increased knee valgus at landing and
      fatigue relative to males during jump-landing performance. Overall, there was a
      trend of improved jump-landing performance with maturation.

PMID- 30222477
TI  - Hip and Trunk Muscle Activity During the Star Excursion Balance Test in Healthy
      Adults.
AB  - CONTEXT: Dynamic balance (DB) is a measure of core stability. Deficits in the DB
      have been related to injuries in the athletic populations. The Star Excursion
      Balance Test (SEBT) is suggested to measure and improve DB when used as a
      rehabilitative tool. OBJECTIVE: To determine the electromyographic (EMG) activity
      of the hip and the trunk muscles during the SEBT. DESIGN: Descriptive. SETTING:
      University campus. PARTICIPANTS: Twenty-two healthy adults (11 males and 11
      females) (23.3 +/- 3.8 years, 170.3 +/- 7.6 cm, 67.8 +/- 10.3 kg, and 15.1 +/-
      5.0 %body fat). INTERVENTION: Surface EMG data were collected on 22 healthy
      adults of the erector spinae (ES), external oblique (EOB), and rectus abdominis
      (RA) bilaterally and gluteus medius (GMED) and gluteus maximus (GMAX) muscle of
      the stance leg. A Two-way repeated measures ANOVA was used to determine the
      interaction between the percentage maximal voluntary isometric contraction
      (%MVIC) and the reach directions. The %MVIC for each muscle was compared across
      the eight reach directions using the Sidak post hoc test with alpha at .05. MAIN
      OUTCOME MEASURES: %MVIC. RESULTS: Significant differences were observed for all
      the eight muscles. Highest EMG activity was found for the tested muscles in the
      following reach directions Ipsilateral (i) EOB (44.5 +/- 38.4%): anterolateral,
      Contralateral (c) EOB (52.3 +/- 40.8%): medial, iRA (8 +/- 6.6%): anterior, cRA
      (8 +/- 5.3%): anteromedial, iES (46.4 +/- 20.2%): posterolateral, cES (33.5 +/-
      11.3%): posteromedial, GMAX (27.4 +/- 11.7 %): posterior, and GMED (54.6 +/-
      26.1%): medial direction. CONCLUSIONS: Trunk and hip muscle activation was
      direction dependent during the SEBT. This information can be used during
      rehabilitation of the hip and the trunk muscles.

PMID- 30222478
TI  - Motoneuron Function Does Not Change Following Whole-Body Vibration in Individuals
      With Chronic Ankle Instability.
AB  - CONTEXT: Following a lateral ankle sprain, approximately 40% of individuals
      develop chronic ankle instability (CAI), characterized by recurrent injury and
      sensations of giving way. Deafferentation due to mechanoreceptor damage post
      injury is suggested to contribute to arthrogenic muscle inhibition (AMI). Whole
      body vibration (WBV) has the potential to address the neurophysiologic deficits
      accompanied by CAI and therefore possibly prevent re-injury. OBJECTIVE: To
      determine if an acute bout of WBV can improve AMI and proprioception in
      individuals with CAI. DESIGN & PARTICIPANTS: We examined if an acute bout of WBV
      can improve AMI and proprioception in individuals with CAI with a repeated
      measures design. Ten young adults with CAI and 10 age-matched healthy controls
      underwent a control, sham, and WBV condition in randomized order. SETTING:
      Biomechanics Laboratory. INTERVENTION: WBV. MAIN OUTCOME MEASURES: Motoneuron
      pool recruitment was assessed via Hoffmann reflex in the soleus. Proprioception
      was evaluated using ankle joint position sense (JPS) at 15 degrees  and 20
      degrees  of inversion. Both were assessed prior to, immediately following and 30
      minutes after the intervention (Pre-test, Post-test, and 30mPost, respectively).
      RESULTS: Soleus H:M ratios were 25% lower in the CAI group compared to the
      control group (p=0.028). JPS mean constant error did not differ between groups
      (p=0.452). Error at 15 degrees  in the CAI (Pre-test 0.8+/-1.6, Post-test 2.0+/
      2.8, 30mPost 2.0+/-1.9) and control group (Pre-test 0.8+/-2.0, Post-test 0.6+/
      2.9, 30mPost 0.5+/-2.1) did not improve post-WBV. Error at 20 degrees  did not
      change post-WBV in the CAI (Pre-test 1.3+/-1.7, Post-test 1.0+/-2.4, 30mPost
      1.5+/-2.2) or control group (Pre-test -0.3+/-3.0, Post-test 0.8+/-2.1, 30mPost
      0.6+/-1.8). CONCLUSION: AMI is present in the involved limb of individuals with
      CAI. The acute response following a single bout of WBV did not ameliorate the
      presence of AMI nor improve proprioception in those with CAI.

PMID- 30222480
TI  - Reply to H.J.A Adams et al and C. Gisselbrecht.

PMID- 30222479
TI  - Safety and efficacy of intravenous iron isomaltoside for correction of anaemia in
      patients with inflammatory bowel disease in everyday clinical practice.
AB  - AIMS: Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel
      disease (IBD), who are often treated with intravenous iron. This observational
      study aimed to investigate the effectiveness and safety of iron isomaltoside in
      routine practical care of IDA in IBD patients. METHODS: The study included 197
      IBD patients designated for treatment with iron isomaltoside. Treatment was
      administered according to routine practice. Data were recorded at baseline and
      after approximately 4, 8, and 16 weeks. Efficacy data included haemoglobin (Hb)
      levels and haematinics, while safety data included adverse drug reactions and
      safety laboratory variables. RESULTS: Patients received a mean (range) cumulative
      dose of 1304 (100-3500) mg iron isomaltoside. Hb increased from 10.7(+/-1.6) g/dL
      at baseline to 13.1(+/-1.5) g/dL at the final visit. In addition, serum iron,
      ferritin and transferrin saturation increased and soluble transferrin receptor
      decreased. Calprotectin decreased, as did IBD symptom scores, Harvey-Bradshaw
      Index (Crohn's disease) and partial Mayo score (Ulcerative colitis). About 8% of
      patients reported transient adverse reactions, most commonly skin reactions,
      nausea and vomiting, and 2% SAEs, most frequently tachycardia. CONCLUSION: Iron
      isomaltoside was demonstrated to be effective and had a good safety profile in
      IBD patients in everyday clinical practice in Germany.

PMID- 30222481
TI  - Unproven Clinical Value of Interim FDG-PET in Aggressive Non-Hodgkin Lymphoma.

PMID- 30222482
TI  - Reply to H.J.A. Adams et al.

PMID- 30222483
TI  - Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphoma:
      Standard of Care After the PETAL Study?

PMID- 30222484
TI  - Modulation of Cortical Activity Induced by High-Frequency Whole-body Vibration
      Exercise: An fNIRS Study.
AB  - CONTEXT: Whole-body vibration (WBV) has shown many positive effects on the human
      body in rehabilitation and clinical settings in which vibration has been used to
      elicit muscle contractions in spastic and paretic muscles. OBJECTIVE: The purpose
      of this study was to investigate whether WBV exercise (WBVe) differently
      modulates the cortical activity associated with motor and prefrontal function
      based on its frequency. METHODS: Eighteen healthy male adults (mean age: 25.3 +/-
      2.4 years) participated in this study and performed WBVe (Galileo Advanced plus,
      Novotec Medical, Pforzheim, Germany) under three different vibration frequency
      conditions (4-mm amplitude with 10-, 20- and 27-Hz frequencies) and a control
      condition (0 mm amplitude with 0-Hz frequency). Each condition consisted of two
      alternating tasks (squatting and standing) every 30 sec for five repetitions. All
      subjects performed the four conditions in a randomized order. MAIN OUTCOME
      MEASURES: Cortical activation during WBVe was measured by relative changes in
      oxygenated hemoglobin (oxyHb) concentration over the primary motor cortex (M1),
      premotor cortex (PM), supplementary motor area (SMA), and prefrontal and
      somatosensory cortices using functional near-infrared spectroscopy (fNIRS).
      RESULTS: OxyHb concentration was higher during the 27-Hz vibration condition than
      the control and 10-Hz vibration conditions. Specifically, these changes were
      pronounced in the bilateral M1s (p < 0.05) and right prefrontal cortex (p <
      0.05). In contrast, no significant changes in oxyHb concentration were observed
      in any of the cortical areas during the 10-Hz vibration condition compared with
      control condition. CONCLUSION: This study provides evidence that the motor
      network and prefrontal cortical areas of healthy adult males can be activated by
      27-Hz WBVe. However, WBVe at lower frequencies did not induce significant changes
      in cortical activation.

PMID- 30222485
TI  - The Effect of Concussive Injury on Individual Game Performance in Professional
      Collision Sport Athletes.
AB  - Clinical Scenario: Collision sports are often at higher risk of concussion due to
      the physical nature and style of play. Typically, initial clinical recovery
      occurs within 7-10 days; however, even this timeframe may result in significant
      time lost play. Little has been done in previous research to analyze how
      individual game performance may be affected upon return to play post-concussion.
      Focused Clinical Question: Upon return-to-play clearance, how does sport-related
      concussion affect game performance of professional athletes in collision sports?
      Summary of Key Findings: All 3 studies included found no significant change in
      individual performance of professional collision-sport athletes upon returning to
      play from concussive injury. One of the studies indicated that there was no
      difference in performance for NFL athletes who did not miss a single game
      (returned within 7 days) and those who missed at least 1 game. One study
      indicated that while there was no change in performance of NFL players upon
      returning to play from sustained concussion, there was a decline in performance
      in the 2 weeks before the diagnosed injury and appearing on the injury report.
      The final study indicated that there was no difference in performance or style of
      play of NHL athletes who missed time due to concussive injury when compared to
      athletes who missed games for a non-injury factor. Clinical Bottom Line: There
      was no change in performance upon return from concussive injury, suggesting that
      players appear to be acutely recovered from the respective concussion before
      returning to play. This suggests that current policies and management properly
      evaluate and treat concussed athletes of these professional sports. Strength of
      Recommendation: Grade C evidence exists that there is no change in individual
      game performance in professional collision-sport athletes before and after
      suffering a concussion.

PMID- 30222486
TI  - Population-Based Survey Methods for Reaching Adolescent and Young Adult Survivors
      of Pediatric Cancer and Their Parents.
AB  - PURPOSE: Contacting childhood cancer survivors (CCS) to assess reasons for
      declining receipt of follow-up care after treatment is difficult and
      participation in surveys may be low, resulting in biased results. We sought to
      demonstrate effective recruitment and population-based sampling methods to
      improve response and minimize bias. METHODS: Four hundred and seventy CCS
      diagnosed between 2000 and 2007 at two hospitals in Los Angeles County were
      selected from the California Cancer Registry and were 15-25 years of age at the
      time of interview. Surveys of survivors and their parents were completed by
      multiple methods including mail, online, and telephone. Effectiveness of "plain"
      versus "designer" formatting of study materials was tested. Variables associated
      with response were analyzed using univariate and multivariable methods. Effort
      required for recruitment was quantified. RESULTS: Fifty percent of survivors (n =
      235) and 36.5% of parents (n = 171) responded, and there were 160 parent-child
      dyads among them. Among located survivors, 61% participated. Response was higher
      for women, parents of younger survivors, and those from higher socioeconomic
      status areas. Among Hispanics, no variables were related to response. More effort
      was required to reach men and older survivors, but efforts beyond 15 calls and 7
      remailings were unproductive. Formatting (i.e., plain vs. designer) did not
      affect response. CONCLUSION: Efforts to reach survivors must include multiple
      methods to be successful. Use of an intensive recruitment strategy and population
      based sample resulted in a largely representative sample of CCS, especially for
      Hispanics. Expensive design efforts had little effect on recruitment, suggesting
      that plainer materials are sufficient. This example may inform similar studies.

PMID- 30222487
TI  - Leptospirosis in Urban and Suburban American Black Bears in Western North
      Carolina.
AB  - American black bear ( Ursus americanus) populations in North Carolina have
      recovered significantly in recent decades and now occupy much of western North
      Carolina, including urban-suburban areas. We used the black bear as a potential
      sentinel for leptospirosis, a bacterial zoonotic disease caused by Leptospira
      spp., which is maintained by domestic and wild mammals. We determined whether
      Leptospira spp. were present across a gradient of housing densities in the urban
      and suburban black bear population in and around Asheville, North Carolina using
      serologic and molecular surveys. We collected blood from captured black bears (
      n=94) and kidneys and bladders from carcasses ( n=19). We tested a total of 96
      (47 females, 47 males, and 2 unknown) serum samples by microscopic agglutination
      test (MAT) and had positive results (titer >1:100) for L. kirschneri serovar
      Grippotyphosa ( L. Grippotyphosa) in 4 females (8%) and 5 males (10%). No other
      serovars showed elevated titers in MAT. We tested a total of 125 samples using
      PCR ( n=96 serum, n=20 kidney, and n=9 bladders) and obtained positive results
      from one serum (1%), one kidney (5%), and one bladder (11%). The presence of
      Leptospira spp. in black bears occupying an urban and suburban landscape may
      indicate a more extensive occurrence of the bacteria among animals in the study
      region because black bears are the top carnivore in that ecosystem. Potential
      threats of widespread contamination during natural events such as flood or
      drought must be considered.

PMID- 30222488
TI  - Which Plant Part of Purple Coneflower (Echinacea purpurea (L.) Moench) Should be
      Used for Tea and Which for Tincture?
AB  - Medicinal plants are widely used for the relief of disease symptoms or as dietary
      supplements. In recent decades, purple coneflower has become extremely well
      known. An infusion or tincture of purple coneflower can be prepared by anyone
      simply, inexpensively, and ecologically safely. Three plant parts of purple
      coneflower were used in the study: extracts from roots, flowers, and leaves were
      obtained using three different solvents (100% and 40% ethanol and water). High
      performance liquid chromatography-mass spectrophotometer identified and
      quantified 23 individual phenolics. Pure (100%) ethanol gave the lowest yield of
      all the investigated phenolic compounds in all herb parts. Chicoric and caftaric
      acids were the major phenolic compounds in coneflower. Caftaric acid, with health
      promoting properties, was extracted best in a water solution from purple
      coneflower leaves (2673.31 mg/100 g dry weight [DW]) and chicoric acid, also with
      a beneficial effect on human health, yielded the highest levels in 40% ethanol
      solution from flowers (1571.79 mg/100 g DW) and roots (1396.27 mg/100 g DW).

PMID- 30222489
TI  - Comparing the Effects of SUREE Programs on People With Scapular Downward Rotation
      Syndrome: Randomized Clinical Trial.
AB  - CONTEXT: Scapular downward rotation syndrome (SDRS) is an impaired alignment that
      causes shoulder and neck pain. Interventions may lead to the reduction of pain
      intensity and joint position error (JPE) and improve range of motion (ROM).
      OBJECTIVES: To evaluate the effects of 6-week Scapular Upward Rotation and
      Elevation Exercises (SUREE) with and without visual feedback on pain, ROM and JPE
      in people with SDRS. STUDY DESIGN: Randomized Control Trial. SETTING:
      Institutional practice. PARTICIPANTS: 42 young and active subjects (22.61 +/-
      1.80 years, 27 males and 15 female) with unilateral SDRS randomly assigned into
      three groups (two intervention groups and one control group). INTERVENTIONS:
      SUREE without and with visual feedback programs. MAIN OUTCOME MEASURES: Pain,
      neck flexion and rotation ROMs, and JPE were measured using Visual Analog Scale
      (score), Double Inclinometer Method, Universal Goniometer Method (degree), and a
      dual digital inclinometer (degree) respectively before and after interventions.
      RESULTS: The results showed statically significant changes within the
      experimental groups in all variables except for the neck rotation ROM in the
      SUREE intervention without visual feedback (p < 0.05). However, there were no
      changes in the control group before and after the interventions in all dependent
      variables (p < 0.05). Also, there were no significant differences between both
      experimental groups concerning all dependent variables except for the rotation
      ROM (p<0.05). CONCLUSION: The results suggest that the 6-week SUREE with and
      without visual feedback programs result in decreased neck pain and improved
      flexion ROM, and JPE during active neck motions in subjects with unilateral SDRS.
      However, the 6-week SUREE with visual feedback may improve the neck rotation ROM
      in subjects with unilateral SDRS. However, further studies are needed to confirm
      the results of this study.

PMID- 30222490
TI  - Prolonged Amenorrhea and Resumption of Menses in Women with HIV.
AB  - OBJECTIVE: To compare etiologies of prolonged amenorrhea in a cohort of HIV
      infected women with a cohort of similar uninfected at-risk women. MATERIALS AND
      METHODS: Women from the Women's Interagency HIV Study were seen every 6 months,
      and completed surveys including questions about their menstruation. Those who
      reported no vaginal bleeding for at least 1 year ("prolonged amenorrhea") with
      subsequent resumption of bleeding were compared with women in whom bleeding had
      stopped permanently ("menopause"). Characteristics associated with reversible
      prolonged amenorrhea were ascertained. RESULTS: Of 828 women with prolonged
      amenorrhea, 37.6% had reversible amenorrhea and 62.4% never resumed menses. HIV
      seropositive women with prolonged amenorrhea were significantly younger at
      cessation of menses than HIV-negative women (p < 0.0001). Of those with
      reversible prolonged amenorrhea, approximately half were taking medications
      associated with amenorrhea, including 95 (30.6%) hormonal contraception, 80
      (25.7%) opiates/stimulants, 16 (5.1%) psychotropic medications, and 6 (1.9%)
      chemotherapy. HIV-seropositive women were less likely to have medications as a
      cause of amenorrhea than seronegative women (p = 0.02). In multivariable
      analysis, women with reversible prolonged amenorrhea of unknown etiology were
      younger (p < 0.0001), more often obese (p = 0.03), and less educated (p = 0.01)
      than those with permanent amenorrhea. Among HIV-seropositive women, markers of
      severe immunosuppression were not associated with prolonged amenorrhea.
      CONCLUSION: Women with HIV infection have unexplained prolonged amenorrhea more
      often than at-risk seronegative women. This is especially common among obese,
      less-educated women. Prolonged amenorrhea in the HIV-seropositive women should be
      evaluated and not be presumed to be to the result of menopause.

PMID- 30222491
TI  - Effect of Lower Limb Muscle Fatigue on Ground Reaction Force Components During
      Landing in People With Non-Specific Chronic Low Back Pain.
AB  - CONTEXT: The link between landing parameters and lower limb muscle fatigue in
      association with chronic low back pain (CLBP) is not well understood. OBJECTIVE:
      The purpose of this study was to examine the effects of fatigue on the ground
      reaction force (GRF) components during landing in people with non-specific CLBP.
      DESIGN: Quasi- Experimental study. SETTING: Clinical Biomechanics Laboratory.
      PARTICIPANTS: Forty-four subjects were equally divided into a healthy group and a
      group with CLBP. MAIN OUTCOME MEASURES: The GRF along anterior-posterior(y), and
      medial-lateral (x) and vertical (z) axes, time to peak (TTP), the rate of force
      development (RFD), impulses for all axes were calculated. A repeated-measures
      ANOVA (group x fatigue) was used to compare the data among groups. RESULTS: In
      the unfatigued conditions, the amplitudes of Fy3, Fz2, and TTP of Fy1, Fy2, Fz1,
      Fz2, Fz3, Fz4, RFD in Y in the CLBP subjects are significantly different than
      those in the healthy subjects (P<0.05). In the fatigued conditions, the
      amplitudes of Fz2, Fz3, F4, and TTP of Fy2, Fy3, Fy4, Fz2, Impulses of X2, Z in
      the CLBP group were significantly different than those in the healthy
      subjects(P<0.05). Within-group comparisons of measured Fx1, Fy1, Fy2, Fz2, Fz4,
      and TTP of Fx1, Fy1, Fy2, Fz2, Fz3, Fz4, Impulses of X2, z were significantly
      different from pre- to post-fatigue in the healthy group(P<0.05). Within-group
      comparisons of measured Fx1, Fy1, Fz1, Fz2, and TTP of Fx5, Fz1, Impulses of X2
      significantly differed from pre-to post-fatigue in the CLBP group(P<0.05).
      CONCLUSIONS: It seems that TTP of GRF variables in CLBP may have clinical values
      for rehabilitation. Muscle fatigue altered landing performance. While CLBP
      patients will respond differently to lower extremity fatigue. These altered
      variables in LBP patients are the cause of future injuries or lower extremity
      injuries need to be addressed in further studies.

PMID- 30222492
TI  - Activation of Scapular and Lumbopelvic Muscles During Core Exercises Executed on
      Whole-Body Wobble Board.
AB  - CONTEXT: Previous studies highlighted that exercises executed on unstable
      surfaces can yield important benefits to the function of the core musculature in
      rehabilitation and general conditioning settings, and also in athletic training,
      when properly introduced within a periodized training schedule. No previous study
      has analyzed core-stability exercises executed in lying, quadruped, plank, and
      bridge positions on a whole-body wobble board (WWB) specifically designed to
      accommodate the exerciser's entire body and promote whole-body instability. We
      have designed a WWB allowed to roll in a plane perpendicular to its longitudinal
      axis, to promote proactive and reactive activation of the core muscles with a
      transverse or diagonal line of action, which provide trunk and pelvic stability
      with low spine compression forces. PURPOSE: To determine the effect of the use of
      this newly designed WWB by assessing differences in core-muscle activity during
      core-stability exercises performed on the ground, in stable condition, and on the
      WWB. DESIGN: Controlled laboratory study. SETTING: Research laboratory. PATIENTS
      OR OTHER PARTICIPANTS: Eighteen participants recruited from fitness centers.
      INTERVENTION(S): The electomyographic (EMG) activity of lumbopelvic and scapular
      muscles has been recorded during core-stability exercises executed on the WWB
      (unstable condition) and on ground (stable condition). MAIN OUTCOME MEASURE(S):
      Mean and peak EMG activity were compared between stable and unstable condition
      with paired t-tests or Wilcoxon signed-rank tests. RESULTS: Overall, exercises
      performed on the WWB yielded significantly higher EMG activity in the serratus
      anterior and anterolateral abdominal muscles, compared to the same exercises
      executed on the ground. Conversely, for the bird dog exercise, lower-back muscle
      activity was significantly higher on the ground. CONCLUSION: As compared to the
      ground, core-stability exercises executed on WWB constitute a simple and
      effective strategy to increase the activity level of the core muscles that
      control transverse-plane lumbopelvic and trunk stability, avoiding the use of
      external overload.

PMID- 30222493
TI  - Is There a Role for GPS in Determining Functional Ankle Rehabilitation
      Progression Criteria? A Preliminary Study.
AB  - CONTEXT: Contemporary developments in GPS technology present a means of
      quantifying mechanical loading in a clinical environment with high ecological
      validity. However, applications to date have typically focussed on performance
      rather than rehabilitation. OBJECTIVE: To examine the efficacy of GPS micro
      technology in quantifying the progression of loading during functional
      rehabilitation from ankle sprain injury, given the prevalence of re-injury and
      need for quantifiable monitoring. Furthermore, to examine the influence of unit
      placement on the clinical interpretation of loading during specific functional
      rehabilitation drills. DESIGN: Repeated measures. SETTING: University athletic
      facilities. PARTICIPANTS: 22 female intermittent team sports players.
      INTERVENTION: All players completed a battery of 5 drills (anterior hop,
      inversion hop, eversion hop, diagonal hop, diagonal hurdle hop) designed to
      reflect the mechanism of ankle sprain injury, and progress functional challenge
      and loading. MAIN OUTCOME MEASURES: GPS-mounted accelerometers quantified uni
      axial PlayerLoad for each drill, with units placed at C7 and the tibia. Main
      effects for drill type and GPS location were investigated. RESULTS: There was a
      significant main effect for drill type (P<0.001) in the medio-lateral (n2=0.436),
      anterio-posterior (n2=0.480), and vertical planes (n2=0.516). The diagonal hurdle
      hop elicited significantly greater load than all other drills, highlighting a non
      linear progression of load. Only medio-lateral load showed evidence of
      progressive increase in loading. PlayerLoad was significantly greater at the
      tibia than at C7 for all drills, and in all planes (P<0.001, n2>=0.662).
      Furthermore, the tibia placement was more sensitive to between-drill changes in
      medio-lateral load than the C7 placement. CONCLUSIONS: The placement of the GPS
      unit is imperative to clinical interpretation, with both magnitude and
      sensitivity influenced by the unit location. GPS does provide efficacy in
      quantifying multi-planar loading during (p)rehabilitation, in a field or clinical
      setting, with potential in extending GPS analyses (beyond performance metrics) to
      functional injury rehabilitation and prevention.

PMID- 30222494
TI  - The Effect of a 20-Week Corrective Exercise Programme on Functional Movement
      Patterns in Youth Elite Male Soccer Players.
AB  - CONTEXT: Poor functional movement patterns negatively affect the ability to
      perform fundamental movements with precision and efficiency, increasing injury
      risk in athletes. OBJECTIVES: To examine the effect of a 20-week corrective
      exercise programme during the competitive season on functional movement patterns
      in youth elite male soccer players. DESIGN: Cohort Study. SETTING: Team
      facilities. PARTICIPANTS: 65 youth elite male soccer players (age 15.89 +/- 0.53
      years; weight 67.42 +/- 6.78 kg; stature 175.20 +/- 6.34 cm). Two of four teams
      were randomly selected to take part in the corrective programme. Thus, the
      players were placed into two groups: corrective exercise programme (CEP) and
      control group (CON). INTERVENTION: Corrective exercise programme. MAIN OUTCOME
      MEASURES: Functional movement screen (FMS) was used to assess the presence of
      dysfunctional, asymmetrical and painful movements in the players before and after
      the intervention period. In addition to considering the FMS total score
      (FMStotal), we separated the screen into 3 parts: FMSmove, FMSflex and FMSstab. A
      repeated measures ANOVA was conducted to determine the effectiveness of the
      training programme on FMS scores. The chi-square (chi2) test was performed to
      determine whether there were significant changes in the frequencies of asymmetric
      and dysfunctional movements after 20 weeks. RESULTS: No athlete experienced
      severe injuries during the intervention period. There was a significant group by
      time interaction (P < 0.01) for FMStotal, FMSmove and FMSstab, in which only the
      CEP increased their scores after the intervention period (P < 0.05). A chi2
      analysis showed a significant (P < 0.05) decrease in asymmetric and dysfunctional
      movements at the follow-up in CEP, while these changes were not observed in CON.
      CONCLUSIONS: Youth elite soccer players demonstrate a high prevalence of
      asymmetric movements during FMS testing, but their functional movement patterns
      can be improved during the competitive season following a specific corrective
      exercise programme.

PMID- 30222495
TI  - Comparative Effects of Tensioning and Sliding Neural Mobilization on Static
      Postural Control and Lower Limb Hop Testing in Football Players.
AB  - Context Sliding and tensioning neural mobilization are used to restore normal
      function of the nervous system, but impose different stresses to it.
      Particularly, sliding induces greater nerve excursion than tensioning.
      Conceivably, they might impact nervous system function differently. Objective To
      compare the effects of tensioning neural mobilization versus sliding neural
      mobilization of the dominant lower limb on static postural control and hop
      testing. Design Randomized, parallel and double blinded trial.
      Setting/Participants Thirty-seven football players. Intervention(s) Participants
      were randomized into two groups: sliding neural mobilization (n=18) or tensioning
      neural mobilization (n=19) targeting the tibial nerve. Main Outcome Measures
      Static postural sway was assessed with a force plate and functional performance
      with hop tests. Measurements were taken at baseline, after the intervention and
      at 30 minutes follow up. Results There was a significant effect of time for the
      center of pressure total displacement and velocity (p<0.05), for the single leg
      hop test (p<0.05), the 6 meters timed hop test (p<0.05) and the crossover hop
      test (p<0.05), but no significant effect of the intervention. Conclusion Sliding
      and tensioning neural mobilization improved postural control and hop testing in
      football players, and improvements remained 30 minutes after the intervention.
      Additional research examining the influence of neural mobilization on sensory
      motor impairments, postural control and functional performance is needed.

PMID- 30222496
TI  - Using the Selective Functional Movement Assessment (SFMA) for the Evaluation of
      Dancers' Functional Limitations and Dysfunctions: A Critically Appraised Topic.
AB  - : Clinical Scenario: Dancers participate in a functionally demanding activity.
      Athletic participation typically requires the completion of a pre-participation
      examination (PPE), which involves a functional movement screen offering insight
      into potential injury recognition. The Selective Functional Movement Assessment
      (SFMA) was created to measure the status of movement-pattern-related pain and
      dysfunction using regionally interdependent movement to aggravate symptoms and
      exhibit limitations and dysfunctions. Still, a functional assessment has not been
      identified to recognize potential dysfunctions or limitations in this population.
      CLINICAL QUESTION: Does the use of SFMA improve overall evaluation of dancers by
      providing more information on a dancer's overall functional ability and
      limitations? Summary of Key Findings: The literature search discovered 12 studies
      and three books, in which four studies were included (two case reviews, one case
      report, and one original research study) based on the inclusion and exclusion
      criteria. Three of the studies provided clinical case studies utilizing the SFMA
      to improve the patient's dysfunctions, while one study examined the intra- and
      inter-rater reliability of the SFMA. In three studies, participants displayed
      less movement dysfunction. The authors from three of the studies agreed the SFMA
      was a valuable tool for clinicians to use during evaluations, as it provided a
      more holistic view of the patient, discovering dysfunctional movement patterns
      that may better identify the source of injury. Clinical Bottom Line: Low-quality
      evidence, defined as poorly designed case studies, case series and cohort
      studies, exist supporting improvement of overall evaluations when utilizing the
      SFMA. Although the studies were considered low-quality evidence, each included
      study displayed effective use of the SFMA as an overall evaluation that correctly
      identified dysfunctional movement patterns. Strength of Recommendation: Grade C
      evidence exists that the SFMA contributes to the functional evaluation used in
      dancers.

PMID- 30222497
TI  - Corneal Toxicity of Topical Tacrolimus Ointment in Mice with Corneal Epithelial
      Injury.
AB  - PURPOSE: To investigate the effect of tacrolimus ointment on corneal epithelium.
      METHODS: Eight-week-old male BALB/c mice were divided into 3 groups. In group 1,
      no injury was made. In group 2, the central 2-mm corneal epithelium was scraped
      off. In group 3, the whole corneal and limbal epithelium was removed after
      absolute ethanol application. In each group, the corneas were observed and
      treated daily with 0.03% or 0.1% tacrolimus ointment (Protopic(r)). The viability
      of cultivated human corneal epithelial cells was also examined after 24-h
      incubation with various concentrations of tacrolimus. RESULTS: Tacrolimus
      ointment significantly delayed the epithelial healing in corneas with epithelial
      injuries (groups 2 and 3) in dose- and frequency-dependent manners, whereas it
      did not have any effects on uninjured corneas (group 1). The proportion of
      terminal deoxynucleotidyl transferase-mediated nick end labeling-positive cells
      and mRNA levels of inflammatory cytokines were higher in tacrolimus-treated
      corneas, compared with controls. Tacrolimus did not directly reduce the viability
      of corneal epithelial cells in culture. CONCLUSIONS: Topical application of
      tacrolimus ointment onto the ocular surface induced toxicity in the cornea with
      epithelial defects through the impairment of epithelial healing and induction of
      apoptosis.

PMID- 30222498
TI  - Characteristics of Infectious Keratitis in Old and Very Old Patients.
AB  - PURPOSE: The aim of this study was to analyze patient backgrounds, including
      activities of daily living (ADL) and living status, predisposing risk factors,
      causative agents, and severity with infectious keratitis in old (75 < 85 years of
      age) and very old (>=85 years of age) patients. METHODS: We retrospectively
      reviewed 54 old patients who were hospitalized for infectious keratitis. The
      focus occupancy ratio (FOR) was defined as the total focus area/entire cornea
      area. RESULTS: The mean patient age was 82.9 +/- 5.6 years. There were 33 old and
      21 very old patients. Dementia was found in 8 patients (14.8%), but the most
      common predisposing risk factor was post-keratoplasty (15 patients, 27.8%).
      However, 10 patients (18.5%) had unknown risk factors. In all, 16 patients
      (29.6%) had low ADL, including being bedridden or being unable to go outside
      without assistance, and 19 patients (35.2%) lived alone. Causative agents were
      detected in 31 patients (57.4%) and included bacteria in 22 patients and fungi in
      9 patients. Seventeen patients (31.5%) had >25% focus size of the corneal area.
      The average FOR was 12.1% +/- 14.1%, and the mean best-corrected visual acuity
      (BCVA) at the first and final visits was 1.88 +/- 0.71 and 1.52 +/- 1.03 logMAR,
      respectively. Multivariate analyses showed that age correlated with FOR and the
      final BCVA. CONCLUSIONS: Infectious keratitis in old and very old patients is
      likely to be severe due to low ADL and social environment. Ophthalmologists
      should take care to identify keratitis during its early stage in these patients.

PMID- 30222499
TI  - Functional Movement Patterns and Body Composition of High-Level Volleyball,
      Soccer and Rugby Players.
AB  - CONTEXT: Sports practice leads athletes to develop a specific body composition,
      coordination patterns and basic motor skills based on the different tactical and
      physical needs. OBJECTIVES: This study aimed to present and compare a wide range
      of functional movement patterns and body composition (BC) parameters of high
      level male athletes playing different sports, and to determine if there was a
      relationship between the parameters examined. DESIGN: Cross-sectional study.
      SETTING: Team facilities. PARTICIPANTS: Thirty volleyball, twenty-five soccer and
      thirty rugby players (age 25.9+/-5.0 years, BMI 25.6+/-4.1 kg/m2). INTERVENTIONS:
      Functional movement patterns and anthropometric measurements were collected by a
      physician specifically trained. MAIN OUTCOME MEASURES: BMI, fat mass, fat free
      mass, upper arm muscle and fat area, calf muscle and fat area, thigh muscle and
      fat area, and functional movement screen (FMS) scores. In addition to considering
      the FMS total score, we separated the screen into 3 parts: FMSmove, FMSflex and
      FMSstab. RESULTS: The rugby players showed a higher number of asymmetrical and
      dysfunctional movements than the other athletes (p <0.01), while the highest
      scores in FMSflex were obtained by the volleyball players (p <0.01).
      Additionally, most of the asymmetrical and painful movements in the athletes were
      measured on the shoulder mobility test. Muscle and fat areas differed
      significantly among the athletes (p <0.05). Significant associations were found
      between movement patterns and several BC variables. In particular, large negative
      correlations were measured between percentage of fat mass (r = -0.616; p <0.01),
      upper arm fat area (r = -0.519; p <0.01) and FMS total score. CONCLUSIONS:
      Functional movement patterns and BC differ in athletes according to the sport
      practiced. Furthermore, reaching an optimal BC is essential to achieve a
      satisfactory quality of movement.

PMID- 30222500
TI  - Prevalence and Factors Associated With Injuries in Elite Spanish Volleyball.
AB  - CONTEXT: Prevalence studies have been widely carried out on elite volleyball
      players. However, the extent to which specific prevention strategies are used or
      the influence of the sport equipment on the occurrence of injuries have been
      sparsely investigated. OBJECTIVE: To describe the prevalence of injuries
      sustained during one season in elite Spanish volleyball leagues, and to
      investigate the association of injuries with multiple factors such as player
      court position, injury mechanism, type of shoes used when playing or
      participation in prevention activities. DESIGN: Descriptive Cross-Sectional
      Epidemiology Study: Observational study. SETTING: European elite professional
      volleyball. PARTICIPANTS: Professional volleyball players from the elite Spanish
      volleyball. MAIN OUTCOME MEASURES: A self-report questionnaire assessed injury
      presence during a volleyball season. Questions included the type of injury, its
      anatomical location, participation in prevention strategies, the shoe type, the
      injury mechanism, the season period, the period of leave and the treatment
      received. RESULTS: Four hundred and ninety players (71.2% response rate)
      completed and returned the questionnaire. The injury prevalence was 66.9% and the
      average of injuries per player was 0.94+/-0.85 (range: 0-4). Most Spanish elite
      volleyball players participated in prevention programs during the season (90.3%)
      and played volleyball with low-top shoes (83.6%), but these factors were not
      associated with the prevalence of injuries (p>.05). The anatomical regions with
      the most injuries were the ankle, knee and shoulder, and the most common types of
      injury were sprains, tendinopathies and strains, usually occurring during
      blocking and attack actions during the in season period. CONCLUSIONS: Despite
      most of elite volleyball players participating in prevention programs, the
      results reveal a high injury prevalence. Further prospective research on the
      effectiveness of prevention strategies in elite volleyball is needed.

PMID- 30222501
TI  - Preterm Delivery and Maternal Cardiovascular Disease Risk Factors: The Nurses'
      Health Study II.
AB  - BACKGROUND: Preterm delivery has been linked to future maternal cardiovascular
      disease (CVD); however, research investigating clinical CVD risk factors is
      limited. We evaluated whether women who have delivered an infant preterm are at
      higher risk of developing CVD risk factors after adjustment for prepregnancy
      confounders. MATERIALS AND METHODS: We examined the association between preterm
      delivery and incident chronic hypertension, type 2 diabetes mellitus (T2DM), and
      hypercholesterolemia among 57,904 parous women in the Nurses' Health Study II.
      Multivariable Cox proportional hazards models were used to estimate hazard ratios
      (HRs) and 95% confidence intervals (CIs) for the associations between preterm
      delivery in first pregnancy and each CVD risk factor; adjusted cumulative
      incidence curves were computed using the Breslow estimator. RESULTS: Preterm
      delivery (<37 weeks) was associated with HRs of 1.11 (95% CI: 1.06-1.17) for
      chronic hypertension, 1.17 (95% CI: 1.03-1.33) for T2DM, and 1.07 (95% CI: 1.03
      1.11) for hypercholesterolemia, adjusting for age, race/ethnicity, parental
      education, and prepregnancy confounders (e.g., body mass index, smoking, and
      family history). HRs were higher in women who delivered very preterm (<32 weeks)
      and in the first 10 years after first birth. The cumulative incidence of each
      risk factor was highest in women who delivered very preterm. CONCLUSIONS: Women
      with a history of preterm delivery are at higher risk of developing chronic
      hypertension, T2DM, and hypercholesterolemia in the years after pregnancy. This
      increased risk was particularly pronounced in the first 10 years after a preterm
      delivery, indicating that it may be an important time period to implement
      lifestyle interventions.

PMID- 30222502
TI  - Intercellular Communication Is Key for Protective IFNalpha/beta Signaling During
      Viral Central Nervous System Infection.
AB  - A variety of viruses can induce central nervous system (CNS) infections and
      neurological diseases, although the incidence is rare. Similar to peripheral
      infections, IFNalpha/beta induction and signaling constitutes a first line of
      defense to limit virus dissemination. However, CNS-resident cells differ widely
      in their repertoire and magnitude of both basal and inducible components in the
      IFNalpha/beta pathway. While microglia as resident myeloid cells have been
      implicated as prominent sentinels of CNS invading pathogens or insults,
      astrocytes are emerging as key responders to many neurotropic RNA virus
      infections. Focusing on RNA viruses, this review discusses the role of astrocytes
      as IFNalpha/beta inducers and responders and touches on the role of IFNalpha/beta
      receptor signaling in regulating myeloid cell activation and IFNgamma
      responsiveness. A summary picture emerges implicating IFNalpha/beta not only as
      key in establishing the classical "antiviral" state, but also orchestrating cell
      mobility and IFNgamma-mediated effector functions.

PMID- 30222503
TI  - Implementation of Robotic Surgery in a Pediatric Hospital: Lessons Learned.
AB  - BACKGROUND: Since the late 1980s, minimally invasive surgery (MIS) has been one
      of the fastest growing approaches for surgical procedures. However, its
      development has reached a plateau. One of the reasons is the difficulty to
      operate on more complex cases, such as neonatal procedures. Some experts report
      outstanding outcomes for complex operations, but not all surgeons may be able to
      achieve the same results. Is robotic surgery (RS) a solution? METHODS: To answer
      this question, we reviewed the current indications of RS for the pediatric
      population and the steps needed to incorporate the robotic surgical system in a
      children's hospital. We reported our experience and presented our first results
      and the encountered problems. RESULTS: After a year and a half of experience with
      RS, several lessons were learned: (1) the current robotic surgical system cannot
      yet be considered a replacement to conventional MIS, (2) docking is less time
      consuming than expected, (3) postoperative pain is significantly decreased, (4)
      the absence of haptic feedback is still a matter of concern, and (5) costs can be
      afforded by sharing the RS with adult surgeons. CONCLUSIONS: Based on our
      experience, the advantages seem to outweigh the drawbacks as it encourages team
      building and increases overall comfort for the surgeon. However, the current
      literature fails to prove that RS gives better results for pediatric patients.
      New advances in technology will probably help to overcome the encountered
      difficulties and the high costs.

PMID- 30222504
TI  - Successful Infection of Tick Cell Cultures of Rhipicephalus sanguineus (Tropical
      Lineage) with Ehrlichia canis.
AB  - There are two distinct lineages of ticks, Rhipicephalus sanguineus, in South
      America: tropical and temperate lineages. Only the tropical lineage is recognized
      as competent vector for Ehrlichia canis. The epidemiological data of canine
      monocytic ehrlichiosis is congruent with the distribution of the two lineages of
      R. sanguineus. Herein, we report the infection of R. sanguineus (tropical
      lineage) cell cultures with E. canis, after cryopreservation. R. sanguineus
      (tropical lineage) cell identity was confirmed by sequencing using a 16S rDNA
      gene fragment. Tick cell cultures were prepared in L-15B medium supplemented with
      10%, 15%, and 20% Fetal Bovine Serum (FBS), and 10% of Tryptose Phosphate Broth
      (TPB). Cell cultures developed better at the concentration of 20% of FBS.
      Cultures in the fifth harvest (approximately 7 months later) were selected for
      the first infections. Optimal R. sanguineus cell growth and adhesion was observed
      (5.0 * 106 cells/mL, and the population doubling time every 57 h). Once infected
      with E. canis, the cultures were maintained in L-15B medium supplemented with 2%
      and 5% of FBS fortified with iron and 10% TPB. Infected cells were also
      cryopreserved. DNA was extracted from infected and noninfected cells and analyzed
      using quantitative real-time PCR targeting the E. canis-dsb gene. Primary culture
      of the fifth passage was infected by E. canis and it maintained the pathogen for
      at least 40 days before partial cell destruction. Subcultures of infected cells
      (fresh and cryopreserved cultures) onto new tick cell cultures were successful.
      The E. canis infection was confirmed by real-time PCR and light and transmission
      electron microscopy. The R. sanguineus (tropical lineage) cells infected with E.
      canis successfully infected new tick cell cultures, showing that these cells
      could be an alternative substrate for maintenance of this pathogen.

PMID- 30222505
TI  - An Intervention Tool to Increase Patient-Physician Discussion of Lifestyle Risk
      Factors for Breast Cancer.
AB  - BACKGROUND: Risk assessment and discussion of lifestyle in primary care are
      crucial elements of breast cancer prevention and risk reduction. Our objective
      was to evaluate the impact of a breast cancer risk assessment and education tool
      on patient-physician discussion of behaviors and breast cancer risk. MATERIALS
      AND METHODS: We conducted a randomized controlled trial with an ethnically and
      linguistically diverse sample of women, ages 40-74, from two primary care
      practices. Intervention participants completed a tablet computer-based Breast
      Cancer Risk Assessment and Education (BreastCARE) intervention in the waiting
      room before a scheduled visit. Both patients and physicians received an
      individualized risk report to discuss during the visit. Control patients
      underwent usual care. Telephone surveys assessed patient-physician discussion of
      weight, exercise, and alcohol use 1 week following the visit. RESULTS: Among the
      1235 participants, 27.7% (161/580) intervention and 22.3% (146/655) usual-care
      patients were high risk for breast cancer. Adjusting for clustering by physician,
      the intervention increased discussions of regular exercise (odds ratios [OR] =
      1.94, 1.50-2.51) and weight (OR = 1.56, 1.23-1.96). There was no effect of the
      intervention on discussion of alcohol. Women with some college education were
      more likely to discuss their weight than those with high school education or less
      (OR = 1.75, 1.03-2.96). Similarly, non-English speakers were more likely to
      discuss their weight compared with English speakers (OR = 2.33, 1.04-5.22).
      CONCLUSIONS: BreastCARE is a feasible risk assessment tool that can successfully
      promote discussions about modifiable breast cancer risk factors between patients
      and primary care physicians.

PMID- 30222506
TI  - Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans with
      Acute and Chronic Hepatitis B.
AB  - Nod-like receptor protein 3 (NLRP3), absent in melanoma 2 (AIM2), and interferon
      gamma inducible protein 16 (IFI16) are innate immune sensors for intracellular
      microbes, which can be activated by various dangerous signals and subsequently
      lead to caspase-1 (CASP1) activation and the maturation cleavage of effector
      molecules pro-IL-1beta and pro-IL-18. Their roles in immunopathology of acute and
      chronic hepatitis B virus (HBV) infection are still unclear. In this study, we
      first investigated the activation of NLRP3, AIM2, and IFI16 inflammasomes in
      peripheral blood mononuclear cells (PBMCs) from patients infected with acute
      hepatitis B (AHB) and chronic hepatitis B (CHB) by quantitative real-time PCR and
      enzyme-linked immunosorbent assay. We next analyzed the impact of hepatitis B e
      antigen (HBeAg) on activation of AIM2 and IFI16 inflammasomes in PBMCs of CHB
      patients stimulated in vitro with AIM2 and IFI16 agonist ligands, poly (dA:dT)
      and VACA-70mer, respectively. The results showed that the mRNA expression levels
      of AIM2, IFI16, and CASP1 in PBMCs from AHB and CHB patients were both
      upregulated. Furthermore, the mRNA levels of AIM2 and IFI16 in CHB patients were
      significantly positively correlated with serum HBV loads. However, only in
      patients with AHB there was elevation of serum IL-1beta and IL-18. There was no
      activation of NLRP3, AIM2, and IFI16 inflammasomes in CHB patients. Stimulation
      of PBMCs of CHB patients in vitro with poly (dA:dT) and VACA-70mer induced the
      activation of AIM2 and IFI16 inflammasomes, respectively. This ligand-induced
      activation was suppressed by HBeAg. Our results suggest that there exists
      activation of the AIM2 and IFI16 inflammasomes, but not the NLRP3 inflammasome,
      in AHB, and the activation of the AIM2 and IFI16 inflammasomes can be inhibited
      by HBeAg in CHB, which may contribute to HBV-induced immunotolerance.

PMID- 30222507
TI  - Gender Differences in Outcomes Following a Pain-Free, Home-Based Exercise Program
      for Claudication.
AB  - BACKGROUND: Peripheral artery disease (PAD) is a common cardiovascular pathology
      that affects mobility. In previous research, supervised exercise, a recommended
      treatment for claudication, was less effective in women. This study
      retrospectively investigated whether functional outcomes exhibit sex differences
      following a pain-free, home-based exercise program for PAD patients. MATERIALS
      AND METHODS: Patients with PAD and claudication enrolled to a structured home
      based program from 2003 to 2016 were studied. The program was prescribed at the
      hospital and based on two daily 10-minute pain-free walking sessions at
      progressively increasing speed. Outcome measures, which were assessed at baseline
      and discharge, were pain threshold speed (PTS) and maximal (Smax) during a
      treadmill test and pain-free walking distance (PFWD) and total distance walked in
      6 minutes (6MWD). The ankle-brachial index (ABI), program duration, and patient
      adherence were determined. RESULTS: A total of 1007 patients (women; n = 264;
      26%) were enrolled. At baseline, compared to men, women exhibited similar ABI
      values but lower PTS and PFWD values (p < 0.001). At discharge, with similar
      adherence (score 3/4 +/- 1 each) in both groups, superimposable improvements were
      observed for PTS (0.8 +/- 0.8 km/h each), Smax (0.4 +/- 0.5 km/h each), PFWD
      (women 95 +/- 100; men 86 +/- 104), 6MWD (women 32 +/- 65; men 35 +/- 58), and
      ABI (women 0.07 +/- 0.12; men 0.06 +/- 0.11) without between-group differences
      (confirmed after propensity analysis). CONCLUSION: A personalized, structured
      pain-free exercise program for PAD patients performed inside the home for a few
      minutes a day was equally effective in both sexes. Programs favoring adherence
      and functional outcomes in women should be tested in prospective studies.

PMID- 30222508
TI  - A Comparison of Toll-Like Receptor 5 and 21 Ligands as Adjuvants for a
      Formaldehyde Inactivated H9N2 Avian Influenza Virus Vaccine in Chickens.
AB  - Low pathogenic avian influenza virus (AIV) infection in chickens can result in
      economic losses and has impacts on human health. Poultry vaccination is a tool
      that can be used to decrease infection and transmission of AIVs. Prior research
      has demonstrated that Toll-like receptor (TLR) ligands can act as vaccine
      adjuvants and their addition to inactivated AIV vaccines can enhance immune
      responses elicited in chickens. The objective of this study was to compare the
      adjuvant capabilities of TLR5 ligand (flagellin) and TLR21 ligand (CpG ODN 2007)
      administered either alone or in combination with an intramuscular formaldehyde
      inactivated H9N2 whole virus vaccine in chickens. Along with the inactivated
      virus, chickens were administered either a single dose of CpG ODN 2007 (2 or 10
      MUg), flagellin (0.4 or 2 MUg), or a combination of both ligands. An additional
      group received AddaVaxTM, an oil emulsion style adjuvant. Chickens were
      vaccinated twice and serum and lachrymal samples were collected weekly following
      the primary vaccination, and antibody-mediated immune responses were quantified.
      Results showed that vaccines containing CpG ODN 2007 induce significantly greater
      systemic and lachrymal antibody responses than vaccines containing flagellin or
      AddaVax. Combinations of flagellin and CpG ODN 2007 did not demonstrate
      inhibitory, additive, or synergistic effects on systemic or lachrymal antibody
      mediated immune responses. Additionally, for both flagellin and CpG ODN 2007, a
      fivefold higher dose of each did not induce significantly higher antibody
      mediated immune responses compared with the lesser dose. Future studies should
      examine the induction of cell-mediated immune responses when flagellin, CpG ODN
      2007, or other TLR ligands are administered either alone or combined as adjuvants
      for inactivated H9N2 AIV vaccines.

PMID- 30222509
TI  - Does Robot-Assisted Radical Prostatectomy Affect Renal Intravascular Parameters
      and Glomerular Filtration Rate?
AB  - BACKGROUND: We aimed to investigate the effects of intra-abdominal pressure and
      steep Trendelenburg position on the intrarenal vascular parameters and estimated
      glomerular filtration rate (eGFR) in the first 24 hours of robot-assisted radical
      prostatectomy (RARP) surgery. METHODS: We prospectively studied 31 men who
      underwent RARP for prostate cancer in our clinic between September and December
      2017. Preoperative color Doppler ultrasonographic (CDUS) measurements of renal
      intravascular parameters were obtained 24 hours before the operation. Similarly,
      postoperative CDUS measurements were performed 24 hours after RARP. Preoperative
      serum creatinine (Cr) level and eGFR were noted. On the postoperative first day,
      serum Cr levels were checked and eGFR was calculated. RESULTS: The mean age of
      men was 61.9 years, and the mean operation time was 268.5 minutes. No significant
      differences between preoperative and postoperative intrarenal vascular parameters
      were observed (P > .05). Serum creatinine was significantly increased (P = .019),
      but eGFR did not change statistically significant after RARP (P = .144). While
      the change in the mean resistive index (DeltaRI) was affected by intravenous
      (i.v.) infused fluid volume and renal width; the change in the mean pulsatility
      index (DeltaPI) was only affected by renal width. Also, the change in the mean
      peak systolic velocity (DeltaPSV) was related to age, i.v. infused fluid volume,
      and renal parenchymal thickness. Finally, the change in the mean end-diastolic
      velocity (DeltaEDV) was related to age and renal width. CONCLUSION: Renal
      functions and intrarenal vascular parameters return to baseline levels 24 hours
      after RARP.

PMID- 30222510
TI  - Changing the Angulation of the Tooth Germ in the Bony Crypt: A Case Report.
AB  - An ankylosed primary molar may cause rotation or ectopic impaction of
      succedaneous premolar. When conventional treatment modalities such as
      observation, surgical exposure with or without orthodontic traction, and
      autotransplantation are not possible, the simple surgical relocation method could
      be an alternative treatment option for a lingually rotated premolar during the
      tooth germ stage before opting to extraction. In the case reported herein, the
      lingually rotated permanent mandibular second premolar tooth germ was surgically
      relocated within its bony crypt. Continued root development and spontaneous
      eruption were observed without complications during the 3.5-year follow-up
      period.

PMID- 30222512
TI  - African Swine Fever-A Call to Action.

PMID- 30222511
TI  - Transoceanic Telementoring of Tube Thoracostomy Insertion: A Randomized
      Controlled Trial of Telementored Versus Unmentored Insertion of Tube Thoracostomy
      by Military Medical Technicians.
AB  - BACKGROUND: Tension pneumothorax is a frequent cause of potentially preventable
      death. Tube thoracostomy (TT) can obviate death but is invasive and fraught with
      complications even in experienced hands. We assessed the utility of a remote
      international virtual network (RIVN) of specialized mentors to remotely guide
      military medical technicians (medics) using wireless informatics. METHODS: Medics
      were randomized to insert TT in training mannequins (TraumaMan; Abacus ALS,
      Meadowbrook, Australia) supervised by RIVN or not. The RIVN consisted of trauma
      surgeons in Canada and Australia and a senior medic in Ohio. Medics wore a helmet
      mounted wireless camera with laser pointer to confirm anatomy and two-way voice
      communication using commercial software (Skype). Performance was measured through
      objective task completion (pass/fail) regarding safety during the procedure,
      proper location, and secure anchoring of the tube, in addition to remote mentor
      opinion and subjective debrief. RESULTS: Fourteen medics attempted TT, seven
      mentored and seven not. The RIVN was functional and surgeons on either side of
      the globe had real-time communication with the mentees. TT placement was
      considered safe, successful, and secure in 100% of mentored (n = 7) procedures,
      although two (29%) received corrective remote guidance. All (100%) of the
      unmentored attempted and adequately secured the TT and were safe. However, only
      71% (n = 5) completed the task successfully (p = 0.46). Participating medics
      subjectively felt remote telementoring (RTM) increased self-confidence (strong
      agreement mean 5/5 +/- 0); confidence to perform field TT (agreement (4/5 +/- 1);
      and decreased anxiety (strong agreement 5/5 +/- 1). Subjectively, the remote
      mentors felt in 100% of the mentored procedures that "yes" they were able to
      assist the medics (1.86 +/- 0.38), and in 71% (n = 5) felt "yes" they made TT
      safer (2.29 +/- 0.49). CONCLUSIONS: RTM descriptively increased the success of TT
      placement and allowed for real-time troubleshooting from thousands of kilometers
      with a redundant capability. RTM was subjectively associated with high levels of
      satisfaction and self-reported self-confidence. Continued controlled and critical
      evaluation and refinement of telemedical techniques should continue. TRIAL
      REGISTRATION: ID ISRCTN/77929274.

PMID- 30222513
TI  - Ten-Year Native Liver Survival Rate After Laparoscopic and Open Kasai
      Portoenterostomy for Biliary Atresia.
AB  - PURPOSE: Laparoscopic Kasai portoenterostomy (LKP) remains controversial in the
      management of infants with biliary atresia (BA). There are no data reporting the
      10-year native liver survival rate after LKP. The study aims to present the 10
      year native liver survival rate after LKP and complications in native liver
      survivors after Kasai portoenterostomy (KP). METHODS: A retrospective review was
      conducted for 31 consecutive infants with BA who underwent KP by day 75 of life
      in our institute from January 1993 to December 2007. The demographics and
      outcomes of patients after LKP and open KP (OKP) were compared. RESULTS: Eleven
      patients underwent LKP and 20 patients underwent OKP. No statistical difference
      was observed in the age at operation and the preoperative bilirubin level. The
      operative time for LKP was significantly longer than that for OKP (mean 314.5
      minutes versus 271.5 minutes, P = .03). The 10-year native liver survival rate
      was 45% (5/11) after LKP and was 85% (17/20) after OKP (P = .03). Forty percent
      (2/5) of the native liver survivors in the LKP and 71% (12/17) in the OKP
      developed complications within 10 years after KP (P = .23). CONCLUSIONS: The 10
      year native liver survival rate in patients who underwent LKP by 75 days of life
      was 45%. With superior 10-year liver survival rate and comparable complication
      rate after OKP, OKP is still the treatment of choice for BA in our institute.

PMID- 30222514
TI  - Transanal Total Mesorectal Excision for Rectal Cancer: Short Term Outcomes from
      Two Centers.
AB  - BACKGROUND: Rectal cancer is now an increasing problem in both developed and
      developing countries. In the last 7 years, minimally invasive surgery for this
      disease has entered a new era of transanal resection with/without laparoscopic
      assistance. MATERIALS AND METHODS: We present here a prospective study done in
      Egypt (probably the earliest experience) and Spain on the feasibility of hybrid
      NOTES in rectal cancer. RESULTS: From September 2015 till November 2017, 18 cases
      underwent transanal total mesorectal excision with no detected mortality and with
      morbidities in 44% of cases, from which 5 were class III on Clavien-Dindo scale
      requiring intervention. Good quality total mesorectal excision was obtained in
      more than three quarters of our patients. CONCLUSIONS: In our experience, the
      technique was technically demanding with a long learning curve; however, the
      short term results were very good in alliance with other few similar reports.

PMID- 30222516
TI  - Interleukin-6 Rescues Lymphocyte from Apoptosis and Exhaustion Induced by Chronic
      Hepatitis C Virus Infection.
AB  - Chronic hepatitis C virus (HCV) infection appears to trigger the onset of immune
      exhaustion and apoptosis to potentially assist viral persistence inside the host,
      eventually leading to exacerbated conditions of inflammation and
      hepatocarcinogenesis. Growing evidence suggests that spontaneous apoptosis of
      peripheral blood mononuclear cells (PBMCs) could be one of the potential immune
      impairment mechanisms in chronic viral infection. Interleukin-6 (IL-6) is a
      pleiotropic cytokine that plays an essential role in regulating immune and
      inflammatory responses. Owing to its known role in priming T cell growth,
      differentiation, and inhibition of lymphocyte apoptosis, we investigated the
      protective effect of IL-6 in rescuing lymphocytes from apoptosis and functional
      exhaustion in chronic HCV infection. The expression pattern of antiapoptotic (Mcl
      1 and Bcl-2), proapoptotic (caspase-3 and Bim) genes along with interferon gamma
      (IFN-gamma) and T cell inhibitory receptor (TIM-3) was analyzed before and after
      in vitro IL-6 treatment of patient-derived PBMCs. It was observed that the
      expression of antiapoptotic genes, Mcl-1 and Bcl-2 increased (threefolds and
      twofolds, respectively) and there was a considerable downregulation in T cell
      inhibitory receptor (TIM-3) and caspase-3. Similarly, the capacity of PBMCs to
      produce IFN-gamma was also significantly increased (p < 0.001) depicting the
      promising nature of IL-6 in enhancing lymphocyte effector function. Summing it
      up, the study supports the positive role of IL-6 in rescuing PBMC population;
      however, the cytokine alone is not sufficient to sustain the adaptive immunity.
      It could be used as a potential candidate for combinational therapy along with
      other regulatory factors for ex vivo enhancement of lymphocyte and may help in
      moving one step toward adoptive T cell therapy in chronic HCV infection.

PMID- 30222515
TI  - Epstein-Barr Virus Lytic Reactivation Induces IgG4 Production by Host B
      Lymphocytes in Graves' Disease Patients and Controls: A Subset of Graves' Disease
      Is an IgG4-Related Disease-Like Condition.
AB  - Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a newly recognized systemic
      fibroinflammatory disease with characteristic histological findings and high
      serum IgG4 levels. Epstein-Barr virus (EBV) is a persistent herpesvirus in B
      lymphocytes, and we previously reported EBV reactivation-induced Ig production.
      We showed that EBV reactivation induced the production of thyrotropin receptor
      antibodies, the causative antibodies of Graves' disease. In the present study, we
      investigated whether EBV reactivation induced IgG4 production and if EBV-positive
      B cells or IgG4-positive plasma cells are present in the thyroid tissues of
      Graves' disease patients with lymphoplasmacytic infiltration. EBV-encoded small
      RNA1 (EBER1) in situ hybridization and immunohistochemistry for IgG and IgG4 were
      performed on seven resected thyroid tissues with lymphoplasmacytic infiltration
      collected from the thyroids of 11 Graves' disease patients. We then cultured the
      lymphocytes of 13 Graves' disease patients and 14 controls and induced EBV
      reactivation to measure IgG4 levels in culture fluids. We detected EBER1-positive
      cells and IgG4-positive plasma cells in the same area of thyroid tissues. EBV
      reactivated cells with IgG4 on their surface were observed in culture cells, and
      IgG4 production was detected in culture fluids. The IgG4/IgG percentage was
      higher than that in normal serum level. A subset of Graves' disease is an IgG4-RD
      like condition, not an IgG4-RD. EBV reactivation stimulates IgG4 production,
      which may result in high serum IgG4 levels and promote IgG4-positive plasma cell
      infiltration. EBER1 needs to be examined when an increase in IgG4-positive plasma
      cell numbers is noted.

PMID- 30222517
TI  - Outcomes of Ostomy Location in Children: Placement of the Ostomy at the
      Umbilicus.
AB  - PURPOSE: Neonatal exploratory laparotomies are often performed with a
      transumbilical incision in our institution, so umbilical ostomy placement has
      become more common. The purpose of our study is to evaluate the outcomes of
      neonates with ostomy placement at the umbilicus in comparison to more traditional
      stoma locations. MATERIAL AND METHODS: Retrospective study of neonates that
      underwent an exploratory laparotomy with ostomy creation between January 2010 and
      September 2015. Demographics, presentation, feedings, ostomy position,
      postoperative complications, and outcomes were collected. Comparative analysis
      was performed in STATA with P-value <.05 determined as significant. Results
      reported as means +/- standard deviation and medians with interquartile ranges.
      RESULTS: Fifty-four children were included, 37% (n = 20) had stomas at the
      umbilicus. Most common other stoma location was the right lower quadrant (63%, n
      = 34). Necrotizing enterocolitis (NEC) was the most common indication for surgery
      in both groups. Days to stoma output were similar between the two groups, [3 (1,
      6) versus 2 (1, 5), P = .96]. Days to initiation of feeds were delayed in the
      umbilical ostomy group [15 (9.5, 23.5) versus 6 (4, 10), P = .02]. Comparing only
      NEC patients, initiation of feeds was similar [22 (14, 56) versus 15.5 (8, 43), P
      = .73]. Umbilical ostomies had an increase in prolapse/peristomal hernias (7
      versus 3, P = .01), but no patients required operative revision. CONCLUSION:
      Umbilical ostomies had similar time to stoma function compared to other sites,
      but a delay in initiation of oral feeds likely secondary to a higher percentage
      of patients with NEC.

PMID- 30222518
TI  - Access to Dermatological Care with an Innovative Online Model for Psoriasis
      Management: Results from a Randomized Controlled Trial.
AB  - BACKGROUND: Many patients with chronic skin diseases lack regular access to
      dermatologists in the United States and suffer poor clinical outcomes.
      INTRODUCTION: We performed a 12-month randomized controlled trial to evaluate the
      impact of an online, collaborative connected health (CCH) model for psoriasis
      management on access to specialty care. MATERIALS AND METHODS: The 300 enrolled
      patients were randomized to online or in-person care. We compared distance
      traveled as well as transportation and in-office waiting time between the two
      groups and obtained patient and provider perspectives on CCH. RESULTS: At
      baseline, no differences existed between the groups in difficulties obtaining
      specialty care. Over 12 months, the mean (standard deviation [SD]) distance
      traveled to and from appointments was 174.8 (+/-577.4) km/person for the in
      person group and 2.2 (+/-14.2) km/person for the online group (p = 0.0003). The
      mean (SD) time spent on transportation and in-office waiting for in-person
      appointments was 4.0 (+/-4.5) h/person for the in-person group and 0.1 (+/-0.4)
      h/person for the online group (p = 0.0001). Patients found CCH to be safe,
      accessible, equitable, efficient, effective, and patient-centered. Providers
      found CCH to be useful for providing psoriasis care. DISCUSSION: The CCH model
      resulted in significantly less distance traveled as well as transportation and in
      office waiting time compared to in-person care. Both patients and providers were
      highly satisfied with CCH. CONCLUSIONS: The CCH model resulted in increased
      access to specialty care and enabled patient-centered, safe, and effective
      management of psoriasis patients.

PMID- 30222519
TI  - Genotypic Resistance to Quinolone and Tetracycline in Salmonella Dublin Strains
      Isolated from Humans and Animals in Brazil.
AB  - Resistance of Salmonella Dublin strains to quinolones and tetracycline has been
      increasing worldwide. Studies regarding the genotypic resistance traits of
      strains of this serovar isolated in Brazil are scarce. This study aims to examine
      the genetic characteristics of Salmonella Dublin strains isolated in Brazil,
      which are associated with resistance to quinolone and tetracycline. The minimum
      inhibitory concentrations (MICs) of nalidixic acid, ciprofloxacin, and
      tetracycline of the 10 strains sensitive and 21 strains resistant to quinolone
      and tetracycline were determined using Etest.(r) The mutation profiles of the
      gyrA, gyrB, parC, and parE genes were accessed by sequencing, while the presence
      of plasmid-mediated quinolone resistance and tet genes was analyzed by PCR.
      Quinolone-resistant strains presented the amino acid substitutions Ser96->Tyr,
      Ser96->Phe, Asp107->Asn, or Asp108->Gly on the gyrA gene, and the Ser224->Phe and
      Glu231->Asp mutations on the gyrB gene. The qnrA, tet(A), and tet(B) genes were
      detected in 5, 13, and 6 strains, respectively. Analysis of the MIC values
      revealed that 1 and 3 strains presented intermediate and resistant MIC profiles
      to nalidixic acid, respectively; 6 strains presented intermediate MIC profile to
      ciprofloxacin; and 13 strains presented resistant MIC profile to tetracycline. In
      the Salmonella Dublin strains studied, quinolone resistance was mainly related to
      mutation points that led to target alteration in the gyrA and gyrB genes, while
      tetracycline resistance was associated with the presence of tet(A) and/or tet(B)
      genes, with the highest resistance levels detected in strains bearing the tet(B)
      gene. The presence of the aforementioned genotypic resistance traits in
      Salmonella Dublin strains isolated over 33 years in Brazil indicates that
      ciprofloxacin or tetracycline therapy against such strains may fail.

PMID- 30222520
TI  - Did the Highly Pathogenic Avian Influenza A(H7N9) Viruses Emerged in China Raise
      Increased Threat to Public Health?
AB  - The low pathogenic avian influenza A(H7N9) viruses (LPAI) were first identified
      in 2013 and have continued to infect humans since then. It was reported in
      February 2017 that the LPAI H7N9 virus has evolved into highly pathogenic avian
      influenza (HPAI) viruses, potentially increasing the risk for human and poultry.
      We in this study overviewed the emergence, epidemiology, and biological
      characterizations of the HPAI H7N9 viruses for the risk assessment.

PMID- 30222521
TI  - Immunology of West Nile Virus Infection and the Role of Alpha-Synuclein as a
      Viral Restriction Factor.
AB  - West Nile virus (WNV) is a single-stranded RNA flavivirus and is a major cause of
      viral encephalitis worldwide. Experimental models of WNV infection in mice are
      commonly used to define acute neuroinflammatory responses in the brain. Alpha
      synuclein (Asyn) is a protein of primarily neuronal origin and is a major cause
      of Parkinson's disease (PD), a disorder characterized by loss of dopaminergic
      neurons. Both WNV and PD pathologies are largely mediated by inflammation of the
      central nervous system (neuroinflammation) and have overlapping inflammatory
      pathways. In this review, we highlight the roles of the immune system in both
      diseases while comparing and contrasting both protective and pathogenic roles of
      immune cells and their effector proteins. Additionally, we review the current
      literature showing that Asyn is an important mediator of the immune response with
      diverging roles in PD (pathogenic) and WNV disease (neuroprotective).

PMID- 30222522
TI  - Trends in Robotic Pancreaticoduodenectomy and Distal Pancreatectomy.
AB  - BACKGROUND: Pancreatic surgery remains a challenge even to the most experienced
      surgeons. Despite significant advances in the field, morbidity and mortality
      continue to have elevated rates even in specialized, high-volume centers. The
      rise of laparoscopy in the past decades has improved outcomes for patients, but
      remains unused due to the technical complexities involved. METHODS: A literature
      search was performed using PubMed and Google Scholar databases. Key words used in
      the search include: "robotic surgery," "robotic pancreas surgery," "pancreas
      surgery," "minimally invasive pancreas surgery," "robotic
      pancreaticoduodenectomy," and "robotic distal pancreatectomy." The studies
      included in our review were summarized in a patient intervention comparison and
      outcome table. RESULTS: The use of a robotic platform has emerged to counteract
      the more challenging aspects of laparoscopic pancreatic surgery, but incurs a
      high cost. Data, however, show a trend toward ever improving outcomes such as
      operative time, estimated blood loss, and length of stay, while still offering
      the benefits of minimally invasive surgery. CONCLUSION: There is no question that
      the use of robots in surgery will continue to expand, and with this, appropriate
      measures must be taken to ensure patient safety in the form of standardized
      education and certification for the future generation of surgeons considering
      robotic surgery. As robotic pancreatic surgery grows, encouraging data have
      emerged-as surgeons become more skilled and programs gain experience, patients
      are being benefited by this expanding technology. Larger, prospective cohorts
      will also provide more definitive evidence of the benefits of robotic surgery.

PMID- 30222524
TI  - Offspring Caregivers of Chinese Women with Breast Cancer: Their Social Support
      Requests and Provision on Social Media.
AB  - BACKGROUND: Although a number of studies have examined social support needs among
      women with breast cancer, little attention has been paid to the burden and needs
      for social support among their family caregivers, who often report mental and
      physical problems associated with caregiving. OBJECTIVE: This study aims to
      examine the role of social media in providing social support for offspring
      caregivers of breast cancer patients. METHODS: A peer support group, "Having a
      breast cancer patient in my family," was created on Douban ( www.douban.com ),
      one of China's most popular social media sites, to provide social support to
      family caregivers of women with breast cancer. We analyzed the content of 784
      messages in the discussion threads where the latest update fell between January
      2017 and July 2017. RESULTS: The results revealed that the majority of messages
      (n = 690, 88.0%) provided or requested social support, and more than 64.5% of
      these messages (n = 445) were posted by caregivers who were offspring of the
      cancer patients. The results also suggested that these caregivers requested and
      provided informational support more frequently than they did emotional and
      instrumental support. CONCLUSIONS: This study suggests that social media could be
      a plausible platform for offspring caregivers of breast cancer patients to share
      caregiving experiences, access informational resources for their care recipients,
      gain knowledge about breast cancer prevention, and obtain emotional
      encouragement. Theoretical as well as practical implications are discussed.

PMID- 30222523
TI  - Definitive Radiotherapy With SBRT or IMRT Boost for Breast Cancer: Excellent
      Local Control and Cosmetic Outcome.
AB  - The gold standard for breast cancer treatment is surgery, but many women may
      desire to avoid surgery if possible. The purpose of this study was to evaluate
      whether breast cancer could be cured with modern sophisticated radiation
      techniques with good cosmetic outcome. We have treated 18 patients with operable
      breast cancer by conventional whole-breast irradiation followed by stereotactic
      body radiotherapy (primary tumor only) or intensity-modulated radiotherapy (tumor
      plus axillary nodes) boost. The planned doses were 50 Gy in 25 fractions, 18 to
      25.5 Gy in 3 fractions, and 20 Gy in 8 fractions, respectively, for the 3
      modalities. Stereotactic body radiotherapy was delivered with 7 to 9 coplanar and
      noncoplanar fixed beams, and intensity-modulated radiotherapy was given by
      tomotherapy. Chemotherapy and/or hormone therapy was used depending on the stage
      and receptor status. In 9 recent patients, hydrogen peroxide was intratumorally
      injected twice a week before whole-breast irradiation. All treatments were well
      tolerable and there were no grade >=3 toxicities. With a median follow-up period
      of 35 months (range, 8-120 months), only 1 patient developed local recurrence and
      2 patients developed distant metastasis. Overall survival, progression-free
      survival, and local control rates were 93%, 85%, and 92%, respectively, at 3
      years. In 50% of the patients, the irradiated breast became better rounded, and
      the position of the nipple of the irradiated breast became >=1 cm higher compared
      to that of the unirradiated breast. Thus, the treated breasts may be more
      aesthetically favorable than before irradiation in these patients. This may
      become a treatment option for patients with operable breast cancer.

PMID- 30222525
TI  - Prevalence of Enterotoxigenic Staphylococcus aureus and Shiga Toxin Producing
      Escherichia coli in Fish in Egypt: Quality Parameters and Public Health Hazard.
AB  - This study investigated the prevalence of Staphylococcus aureus enterotoxin genes
      and shiga toxin -producing Escherichia coli (STEC) in fish and evaluated quality
      parameters of examined fish. A total of 150 fish samples belonging to 6 species
      (25/each species) were cultured on Baird-Parker agar and eosin methylene blue
      agar. Staphylococcal enterotoxin genes and virulence genes (stx1, stx2, and eaeA
      genes) in E. coli serotypes were determined by multiplex PCR. Aerobic plate count
      (APC), Enterobacteriaceae count, coliform count, and Pseudomonas count were
      performed. Also, levels of total volatile base nitrogen and histamine in fish
      were determined. The prevalence of S. aureus ranged from 4% to 36% and count from
      2 to 4 log10CFU/g. The sed, sea, and seb genes in S. aureus isolates were
      detected with percentages of 40%, 26.6%, and 20%, respectively. The E. coli
      serotype O26 carried stx1, stx2, and eaeA. The APCs, Enterobacteriaceae counts,
      and Pseudomonas counts ranged from 5.1 to 7.2, from 2.01 to 3.9, and from 2.1 to
      3.1 log10 CFU/g, respectively. The most probable number (MPN) of coliform ranged
      from 1.3 to 3.6 log10/g. Levels of total volatile basic nitrogen and histamine
      ranged from 29.2 to 12.2 and from 0.6 to 4.6 mg/100 g, respectively. Also, the
      value of thiobarbituric acid was highly significant (1.1 +/- 0.084 mg MDA/kg) in
      Trachurus mediterraneus samples compared with those levels obtained from other
      fish species. Our findings concluded that those fish species could constitute a
      public health hazard as fish are reservoirs for enterotoxigenic S. aureus and
      Shiga toxin producing E. coli strains. This study highlighted the importance of
      screening of fish for enterotoxigenic S. aureus strains and STEC isolates, and
      also assessing the quality parameters of fish.

PMID- 30222526
TI  - Zebrafish (Danio rerio) as a Model for Sprint Exercise Training.
AB  - Sprint performance is important ecologically and physiologically, and it can
      influence fitness by determining outcomes of predator-prey relationships, for
      example, and it can confer substantial human health benefits. In this article we
      test whether zebrafish (Danio rerio) are a suitable model to test hypotheses
      about the effects and consequences of sprint exercise training, and the
      physiological underpinnings of sprint performance. We show that stage 3 c-starts
      that capture the initial escape response of fish lasting <1 s were repeatable
      within individuals. In addition, somewhat longer constant acceleration protocols
      lasting 10 s (U10s) or 30 s (U30s) were highly repeatable within individuals over
      3, 6, and 23 days. C-starts within individuals were not correlated with either
      U10s or U30s, indicating that these measures reflect different physiological
      aspects of sprinting. Stage 3 c-starts and U10s responded positively to sprint
      exercise training. Our exercise training protocol (5 * 10 s sprints with 5-min
      rest periods on 4 days per week for 3 weeks) was based on the human sporting
      literature, and together, our results indicate that zebrafish are a good model to
      assess the physiological and behavioral consequences of sprint exercise training.

PMID- 30222527
TI  - Comparison of Short-Term Outcomes Between 3D and 2D Imaging Laparoscopic
      Colectomy with D3 Lymphadenectomy for Colon Cancer.
AB  - BACKGROUND: Three-dimensional (3D) imaging for laparoscopy was introduced to
      overcome the limitations of conventional two-dimensional (2D) imaging that lacked
      depth perception and spatial orientation. This study aimed to evaluate the effect
      of 3D imaging in laparoscopic colectomy with D3 lymphadenectomy for colon cancer.
      METHODS: From February 2014 to October 2016, the prospective database of 278
      consecutive patients with colon cancer was analyzed retrospectively; these
      patients underwent laparoscopic surgery with 2D (n = 111) and 3D (n = 167)
      imaging, with curative intent. RESULTS: No difference was found in sex, body mass
      index, history of abdominal surgery, and American Society of Anesthesiologists
      grade between the 3D and 2D groups. The estimated blood loss was less in the 3D
      group than in the 2D group (50 mL [30-100 mL] versus 100 mL [50-100 mL], P <
      .001). The number of resected lymph nodes was higher in the 3D group (n = 47
      [37.5-60] versus 41 [32-51.5], P = .001). However, a difference in operative time
      was not observed in both groups (150 minutes [125-175 minutes] versus 155 minutes
      [135-177.5 minutes], P = .186). Postoperative morbidity was similar in both
      groups (7.8% versus 8.1%, P = 1.000). Time to pass first flatus (3 days [2-4
      days] versus 3 days [3-4 days], P = .746) and postoperative hospital stay (6 days
      [6-8 days] versus 6 days [6-7 days], P = .087) were also similar. CONCLUSIONS:
      This study shows that laparoscopic colectomy with D3 lymphadenectomy for colon
      cancer using 3D laparoscopic systems appears to be beneficial, with less blood
      loss, which should be addressed in prospective studies.

PMID- 30222529
TI  - Single-Site Laparoscopic Percutaneous Extraperitoneal Closure Versus Modified
      Transumbilical Two-Port Laparoscopic Suturing of the Hernia Sac for the Treatment
      of Pediatric Inguinal Hernia: Comparison of the Outcomes of Two Different
      Approaches.
AB  - OBJECTIVE: To evaluate the surgical outcomes of single-site laparoscopic
      percutaneous extraperitoneal closure (SLPEC) and modified transumbilical two-port
      laparoscopic suturing (M-TTLS) of the hernia sac for the treatment of pediatric
      inguinal hernia (PIH) and determine whether one approach was superior to another.
      METHODS: From January 2014 to June 2017, a total of 599 children had undergone
      SLPEC or M-TTLS in our department. SLPEC and M-TTLS were the most frequently
      performed single-site laparoscopic procedures for PIH in our department, which
      represented the extraperitoneal and intraperitoneal approaches, respectively. All
      patients were followed up at the out-patients' clinics and the medical records
      were reviewed with respect to all operative outcomes. RESULTS: There were 412
      patients undergoing SLPEC and 187 patients undergoing M-TTLS, of which 358
      hernias were on the right side, 172 on the left and 69 bilaterally. Two hundred
      and thirty-one unilateral hernias with contralateral patent processus vaginalis
      underwent contralateral repair at the same session. Mean operation time was 10.81
      minutes in unilateral repair and 17.00 minutes in bilateral repairs,
      respectively. The perioperative complications included minor extraperitoneal
      hematoma in four (0.44%) patients, recurrence in one (0.11%), hydrocele in five
      (0.56%), and contralateral metachronous inguinal hernia in three (1.00%). No
      other complication developed in either group. There was no significant difference
      of complications between the two approaches except for the longer operation time
      in M-TTLS. CONCLUSIONS: Both SLPEC and M-TTLS were the safe and effective methods
      for PIH. The complications were comparable for M-TTLS and SLPEC, but operation
      time was significantly longer in M-TTLS than in SLPEC.

PMID- 30222528
TI  - The role of calcium sensing receptors in GLP-1 and PYY secretion after acute
      intraduodenal administration of L-Tryptophan in rats.
AB  - OBJECTIVES: The calcium-sensing receptor (CaSR), the major sensor of
      extracellular Ca2+, is expressed in various tissues, including the
      gastrointestinal tract. Although the essential ligand of CaSR is calcium, its
      activity can be regulated by aromatic L-amino acids. The expression of CaSR on
      enteroendocrine cells suggests that CaSR functions as a physiological amino acid
      sensor for gut hormone release. Here, we investigated the effects of L-tryptophan
      (L-Trp) on rat glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and insulin
      secretion, and the role of CaSR in this mechanism in vivo. METHODS: The effects
      of intraduodenal L-Trp on GLP-1, PYY, and insulin secretion were investigated. A
      CaSR antagonist, NPS 2143, was administered to determine whether CaSR plays a
      role in L-Trp-mediated gut hormone release. Male Wistar rats were divided into L
      Trp, L-Trp+NPS 2143, and L-Trp+vehicle groups. Blood samples were collected,
      before and after the intraduodenal infusions, for determining plasma glucose, L
      Trp, insulin, GLP-1, and PYY levels. RESULTS: Our study showed a significant
      increase in plasma GLP-1 and insulin levels, but not plasma PYY and glucose
      levels, following the acute intraduodenal administration of L-Trp. We
      demonstrated that CaSR plays a role in L-Trp-mediated GLP-1 secretion due to
      attenuation of GLP-1 release with the CaSR antagonist NPS 2143. DISCUSSION: We
      demonstrated that GLP-1, but not PYY, secretion following intraduodenal L-Trp
      administration was mediated through calcium-sensing receptors. This mechanism
      underlying protein sensing in the gastrointestinal system may be important for
      the development of new therapeutic strategies without side effects for obesity
      and diabetes.

PMID- 30222530
TI  - Shape from Contour: Computation and Representation.
AB  - The human visual system reliably extracts shape information from complex natural
      scenes in spite of noise and fragmentation caused by clutter and occlusions. A
      fast, feedforward sweep through ventral stream involving mechanisms tuned for
      orientation, curvature, and local Gestalt principles produces partial shape
      representations sufficient for simpler discriminative tasks. More complete shape
      representations may involve recurrent processes that integrate local and global
      cues. While feedforward discriminative deep neural network models currently
      produce the best predictions of object selectivity in higher areas of the object
      pathway, a generative model may be required to account for all aspects of shape
      perception. Research suggests that a successful model will account for our acute
      sensitivity to four key perceptual dimensions of shape: topology, symmetry,
      composition, and deformation.

PMID- 30222531
TI  - A Life in Vision.
AB  - I was drawn into research in George Wald's laboratory at Harvard, where as an
      undergraduate and graduate student, I studied vitamin A deficiency and dark
      adaptation. A chance observation while an assistant professor at Harvard led to
      the major research of my career-to understand the functional organization of
      vertebrate retinas. I started with a retinal circuit analysis of the primate
      retina with Brian Boycott and intracellular retinal cell recordings in mudpuppies
      with Frank Werblin. Subsequent pharmacology studies with Berndt Ehinger primarily
      with fish focused on dopamine and neuromodulation. Using zebrafish, we studied
      retinal development, neuronal connectivity, and the effects of genetic mutations
      on retinal structure and function. Now semi-retired, I have returned to primate
      retinal circuitry, undertaking a connectomic analysis of the human fovea in
      Jeffrey Lichtman's laboratory.

PMID- 30222532
TI  - Corollary Discharge Contributions to Perceptual Continuity Across Saccades.
AB  - Our vision depends upon shifting our high-resolution fovea to objects of interest
      in the visual field. Each saccade displaces the image on the retina, which should
      produce a chaotic scene with jerks occurring several times per second. It does
      not. This review examines how an internal signal in the primate brain (a
      corollary discharge) contributes to visual continuity across saccades. The
      article begins with a review of evidence for a corollary discharge in the monkey
      and evidence from inactivation experiments that it contributes to perception. The
      next section examines a specific neuronal mechanism for visual continuity, based
      on corollary discharge that is referred to as visual remapping. Both the basic
      characteristics of this anticipatory remapping and the factors that control it
      are enumerated. The last section considers hypotheses relating remapping to the
      perceived visual continuity across saccades, including remapping's contribution
      to perceived visual stability across saccades.

PMID- 30222533
TI  - Retinal Vasculature in Development and Diseases.
AB  - The retina is one of the most metabolically active tissues in the body, consuming
      high levels of oxygen and nutrients. A well-organized ocular vascular system
      adapts to meet the metabolic requirements of the retina to ensure visual
      function. Pathological conditions affect growth of the blood vessels in the eye.
      Understanding the neuronal biological processes that govern retinal vascular
      development is of interest for translational researchers and clinicians to
      develop preventive and interventional therapeutics for vascular eye diseases that
      address early drivers of abnormal vascular growth. This review summarizes the
      current knowledge of the cellular and molecular processes governing both
      physiological and pathological retinal vascular development, which is dependent
      on the interaction among retinal cell populations, including neurons, glia,
      immune cells, and vascular endothelial cells. We also review animal models
      currently used for studying retinal vascular development.

PMID- 30222534
TI  - Vision During Saccadic Eye Movements.
AB  - The perceptual consequences of eye movements are manifold: Each large saccade is
      accompanied by a drop of sensitivity to luminance-contrast, low-frequency
      stimuli, impacting both conscious vision and involuntary responses, including
      pupillary constrictions. They also produce transient distortions of space, time,
      and number, which cannot be attributed to the mere motion on the retinae. All
      these are signs that the visual system evokes active processes to predict and
      counteract the consequences of saccades. We propose that a key mechanism is the
      reorganization of spatiotemporal visual fields, which transiently increases the
      temporal and spatial uncertainty of visual representations just before and during
      saccades. On one hand, this accounts for the spatiotemporal distortions of visual
      perception; on the other hand, it implements a mechanism for fusing pre- and
      postsaccadic stimuli. This, together with the active suppression of motion
      signals, ensures the stability and continuity of our visual experience.

PMID- 30222535
TI  - Geometry of Pictorial Relief.
AB  - Pictorial relief is a quality of visual awareness that happens when one looks
      into (as opposed to at) a picture. It has no physical counterpart of a
      geometrical nature. It takes account of cues, mentally identified in the tonal
      gradients of the physical picture-pigments distributed over a planar substrate.
      Among generally recognized qualities of relief are color, pattern, texture,
      shape, and depth. This review focuses on geometrical properties, the spatial
      variation of depth. To be aware of an extended quality like relief implies a
      "depth" dimension, a nonphysical spatial entity that may smoothly vary in a
      surface-like manner. The conceptual understanding is in terms of formal geometry.
      The review centers on pertinent facts and formal models. The facts are
      necessarily so-called brute facts (i.e., they cannot be explained
      scientifically). This review is a foray into the speculative and experimental
      phenomenology of the visual field.

PMID- 30222537
TI  - First-Fit versus Programmed Fit: Is There Quantifiable Benefit in the Custom
      Fitting of Hearing Aids?

PMID- 30222538
TI  - A Nonsense Consonant-Vowel-Consonant Word Test to Assess Auditory Processing.
AB  - BACKGROUND: Dichotic listening (DL), or how the two ears work together as a team,
      is often used in the assessment of auditory processing disorders in both children
      and adults. Currently, the battery of dichotic tests includes stimuli containing
      words, digits, and nonsense consonant-vowel syllables. Single-syllable nonsense
      words are of particular use in assessing processing abilities because they can
      evaluate auditory processing without a listener's dependence on linguistic
      knowledge. Therefore, nonsense words may assess auditory processes independently
      of previous vocabulary knowledge. PURPOSE: This study is designed to assess the
      clinical applicability and face validity of a nonsense word DL test in a young
      adult population. RESEARCH DESIGN: This study included an experimental design to
      investigate the performance of young adult listeners on a Dichotic Nonsense Word
      (DNW) test spoken by a male and female speaker. The results were compared with
      one study that investigated young adult listener's performance on dichotic tests
      of English words. STUDY SAMPLE: A total of 100 young adult participants were
      recruited from the School of Health and Rehabilitation Sciences at the University
      of Pittsburgh to participate in the study. The participants ranged in age from 20
      to 30, with an average age of 23, and all participants had normal hearing. DATA
      COLLECTION AND ANALYSIS: DL performance was measured in all participants using
      the Dichotic Words Test (DWT) and the newly developed DNW test. Kolmogorov
      Smirnoff tests of normality were used to assess distribution of right- and left
      ear scores. Criterion cutoff scores were determined for the percent correct
      scores in the nondominant ear and dominant ear and for ear advantage. RESULTS:
      Scores were significantly different between the two tests in the right ear, Z = 
      8.258, p < 0.001, and in the left ear, Z = -8.471, p < 0.001. Scores within each
      test were higher for the right ear than for the left ear, and scores for both
      ears were significantly lower on the DNW test than for the DWT. Ear advantage
      scores from the DNW test were significantly larger than those obtained from the
      DWT. The low and high 95% criterion cutoff ranges for the DNW test were
      considerably wider than the 95% criterion cutoff ranges for the DWT. CONCLUSIONS:
      Results indicate that the new DNW test may be a useful clinical tool within a
      test battery for evaluating auditory processing skills independent of vocabulary
      knowledge.

PMID- 30222536
TI  - Review of vaccination in pregnancy to prevent pertussis in early infancy.
AB  - Maternal pertussis vaccination has been introduced in several countries to
      protect infants from birth until routine infant vaccination takes place. This
      review assesses existing evidence on the effectiveness and safety of immunization
      in pregnancy. The search was finalized in April 2017 and was based on searches
      using several databases. The selection criteria included any experimental or
      observational study reporting on the immunogenicity, effectiveness or safety of
      vaccination with a pertussis-containing vaccine in pregnant women and their
      infants. Following de-duplication and exclusions, we identified 8395 studies,
      which were reduced to 46 for inclusion. The overall risk of bias was low, with
      the exception of some early studies and pharmacovigilance safety data. The
      evidence demonstrates efficient transplacental transfer of maternal antibodies in
      infants whose mothers were vaccinated with Tdap or Tdap/IPV in pregnancy, with
      good evidence that this protects against disease in young infants. Safety studies
      covering more than 150 000 women vaccinated mostly in the late second or third
      trimesters are generally consistent and provide reassurance of no significant
      increased risk of recognized maternal conditions or of adverse events (including
      congenital anomalies) in infants born to vaccinated women. The clinical
      significance of reduced seroconversion to pertussis following routine
      immunization is not yet clear, but no increased risk of pertussis in infants
      whose mothers were vaccinated in pregnancy was found following primary
      immunizations in North American and English studies. Most post-booster studies
      suggest that any blunting effect is short-lived and that longer-term protection
      in infants from active immunization is not compromised.

PMID- 30222539
TI  - Effects of Secondhand Smoke Exposure on Hearing and Auditory Evoked Potentials,
      ABR and AMLR in Young Adults.
AB  - BACKGROUND: Population health is impacted by environmental secondhand smoke (SHS)
      exposure. Although the negative health effects of SHS exposure include
      respiratory problems in children (nonsmokers) as seen in cigarette smokers, other
      health impacts such as sensory function are not assumed to be the same for both
      passive nonsmokers and smokers. However, hearing loss was recently reported in
      adolescents and aging adults with SHS exposure, suggesting that SHS might impact
      auditory function similarly to cigarette smoking. Specific effects of SHS
      exposure on the central auditory system have not been fully described. PURPOSE:
      To measure auditory function via pure-tone audiometry and evoked potentials in
      young nonsmoking adults aged 18-23 yr who reported exposure to environmental SHS.
      RESEARCH DESIGN: Participants were selected for the SHS-exposed (SHS-E) group
      first, followed by age and gender matched individuals for the SHS-unexposed (SHS
      U) group. Self-reported nonsmoker status was confirmed by biochemical analysis of
      urine for cotinine level. STUDY SAMPLE: Potential participants (N = 208)
      completed a questionnaire about health, smoking history, SHS exposure, and
      hearing ability. Individuals with any neurological conditions, alcohol/drug
      dependencies, excessive noise exposure, using certain medications, or current
      smokers were excluded. Twenty-two nonsmokers in excellent health consented to
      participate. Participants in the SHS-E group reported SHS exposure in home, work,
      or social settings for an extensive time period. Participants in the SHS-U group
      did not live with smokers and reported no SHS exposure, medication use, tinnitus,
      or any chemical exposures. Statistical analysis was conducted on data from 20
      participants, 10 per group with a mean age of 20 yr. DATA COLLECTION AND
      ANALYSIS: Participants underwent auditory procedures in one session in an IAC
      sound-treated room, including otoscopy, tympanometry, pure-tone threshold
      evaluation, auditory brainstem response per ear, and a three-channel auditory
      middle latency response in the right ear. The primary study outcomes were hearing
      thresholds measured (dB HL) at five frequencies, and evoked potential wave
      latencies (I, III, V, Na, Pa, Nb, Pb) and amplitudes (V-I, Na-Pa, Pa-Nb, Nb-Pb).
      It was hypothesized that SHS-exposed individuals would have poorer hearing
      sensitivity (threshold >25 dB HL) and abnormal central auditory function (longer
      latencies; smaller amplitudes) based on evoked potentials. Statistical analyses
      focused on identification of group differences in hearing and central auditory
      function. RESULTS: All participants had normal hearing sensitivity (thresholds
      <=25 dB HL) with no significant group differences. The V/I amplitude ratio in the
      right ear was significantly decreased in SHS-exposed individuals (p < 0.05).
      Auditory brainstem response latencies were not significantly different between
      participant groups or ears. Wave Pb latency was significantly increased in SHS
      exposed individuals (p < 0.01). Auditory middle latency response relative
      amplitudes were significantly different from each other at every electrode site
      (Cz, Fz, C4) but not between groups. Overall, the Na-Pa complex was highest in
      amplitude at all three electrode sites. CONCLUSIONS: This preliminary study
      indicated toxic effects of SHS exposure by evoked potentials with decreased V/I
      amplitude ratio and longer (delayed) Pb latency in young adults. Further studies
      should corroborate these findings to facilitate clinical recommendations.

PMID- 30222540
TI  - An Evaluation of Motivational Interviewing for Increasing Hearing Aid Use: A
      Pilot Study.
AB  - BACKGROUND: Motivational interviewing (MI) has been used in consultation settings
      to motivate hearing aid users to increase hearing aid usage. However, the effect
      of MI on those who use their hearing aids only rarely or not at all has not been
      explored. PURPOSE: The aims of this pilot study were to evaluate the effect of MI
      counseling with elderly hearing aid recipients found to have low hearing aid use
      at a six-month follow-up appointment and to describe clients' subjective
      assessments of their perceived need for hearing aids three months after MI
      counseling. RESEARCH DESIGN: The study had a within-subjects pretest-posttest
      design. STUDY SAMPLE: Forty seven hearing aid recipients who had used their new
      hearing aids, an average of <90 min/day, were recruited at a follow-up
      appointment six months after hearing aid fitting. INTERVENTION: Thirty minutes of
      MI counseling was provided at the six-month follow-up appointment. If needed,
      hearing aid adjustments and technical support were also provided. DATA COLLECTION
      AND ANALYSIS: The effect of MI counseling in combination with adjustments and
      technical support was assessed in relation to datalogged hearing aid use, which
      was assessed immediately before (at the six-month follow-up) and three months
      after (at the nine-month follow-up) the intervention. Hearing aid experiences
      were also assessed three months after MI. RESULTS: Thirty seven participants
      (79%) returned for the nine-month follow-up visit and had modest but significant
      increases in datalogged hearing aid use in the three months following MI
      counseling. Of the 37 participants who returned, 51% had increased their hearing
      aid use to at least 2 h/day after the MI counseling. Most of the 37 participants
      who attended the nine-month follow-up reported increased need for (59%) or
      increased benefit and contentment with (57%) their hearing aid three months after
      MI; these participants also had significantly higher datalogged hearing aid use
      following MI. CONCLUSIONS: These findings suggest that follow-up appointments
      using MI counseling in conjunction with technical support may be useful for
      increasing hearing aid usage among low-users, and a randomized controlled trial
      is warranted.

PMID- 30222541
TI  - Differences in Word and Phoneme Recognition in Quiet, Sentence Recognition in
      Noise, and Subjective Outcomes between Manufacturer First-Fit and Hearing Aids
      Programmed to NAL-NL2 Using Real-Ear Measures.
AB  - BACKGROUND: The American Speech-Language-Hearing Association (ASHA) and American
      Academy of Audiology (AAA) have created Best Practice Guidelines for fitting
      hearing aids to adult patients. These guidelines recommend using real-ear
      measures (REM) to verify that measured output/gain of hearing aid(s) match a
      validated prescriptive target. Unfortunately, approximately 70-80% of
      audiologists do not routinely use REM when fitting hearing aids, instead relying
      on a manufacturer default "first-fit" setting. This is problematic because
      numerous studies report significant differences in REM between manufacturer first
      fit and the same hearing aids using a REM or programmed-fit. These studies
      reported decreased prescribed gain/output in the higher frequencies for the first
      fit compared with the programmed fit, which are important for recognizing speech.
      Currently, there is little research in peer-reviewed journals reporting if
      differences between hearing aids fitted using a manufacturer first-fit versus a
      programmed-fit result in significant differences in speech recognition in quiet,
      noise, and subjective outcomes. PURPOSE: To examine if significant differences
      were present in monosyllabic word and phoneme recognition (consonant-nucleus
      consonant; CNC) in quiet, sentence recognition in noise (Hearing in Noise Test;
      HINT), and subjective outcomes using the Abbreviated Profile of Hearing Aid
      Benefit (APHAB) and the Speech, Spatial and Qualities of Hearing (SSQ)
      questionnaires between hearing aids fit using one manufacturer's first-fit and
      the same hearing aids with a programmed-fit using REM to National Acoustic
      Laboratories Nonlinear Version 2 (NAL-NL2) prescriptive target. RESEARCH DESIGN:
      A double-blind randomized crossover design was used. Throughout the study, one
      investigator performed all REM whereas a second investigator measured speech
      recognition in quiet, noise, and scored subjective outcome measures. STUDY
      SAMPLE: Twenty-four adults with bilateral normal sloping to moderately severe
      sensorineural hearing loss with no prior experience with amplification. DATA
      COLLECTION AND ANALYSIS: The hearing aids were fit using the proprietary
      manufacturer default first-fit and a programmed-fit to NAL-NL2 using real-ear
      insertion gain measures. The order of the two fittings was randomly assigned and
      counterbalanced. Participants acclimatized to each setting for four weeks and
      returned for assessment of performance via the revised CNC word lists, HINT,
      APHAB, and SSQ for the respective fitting. RESULTS: (1) A significant median
      advantage of 15% (p < 0.001; 95% CI: 9.7-24.3%) for words and 7.7% (p < 0.001;
      95% CI: 5.9-10.9%) for phonemes for the programmed-fit compared with first-fit at
      50 dB sound pressure level (SPL) and 4% (p < 0.01; 95% CI: 1.7-6.3%) for words at
      65 dB SPL; (2) No significant differences for the HINT reception threshold for
      sentences (RTS); (3) A significant median advantage of 4.2% [p < 0.04; 95%
      confidence interval (CI): -0.6-13.2%] for the programmed-fit compared with the
      first-fit for the background noise subscale problem score for the APHAB; (4) No
      significant differences on the SSQ. CONCLUSIONS: Improved word and phoneme
      recognition for soft and words for average speech in quiet were reported for the
      programmed-fit. Seventy-nine percent of the participants preferred the programmed
      fitting versus first-fit. Hearing aids, therefore, should be verified and
      programmed using REM to a prescriptive target versus no verification using a
      first-fit.

PMID- 30222542
TI  - Cochlear Implant Practice Patterns: The U.S. Trends with Pediatric Patients.
AB  - BACKGROUND: Many factors affect an individual's outcomes with a cochlear implant
      (CI); however, quality of device programming and consistency of follow-up
      appointments have been shown to be crucial contributors. As audiologists' CI
      caseloads increase, time constraints on appointments also increase, thus fueling
      the need for efficient and effective programming strategies. Currently, there are
      no standardized guidelines describing what methods should be used during
      programming, nor are there standardized schedules that delineate what procedures
      should be performed at specific appointment intervals. Without standardized
      programming guidelines, clinical practices may be variable and may not align with
      best practice research; thus, outcomes with a CI, particularly for pediatrics,
      may not be reflective of the actual potential available. PURPOSE: The purpose of
      this study was to identify the clinical practice patterns used by U.S.
      audiologists when programming and providing follow-up care to children who use
      CIs. This study aimed to determine the following: common programming approaches,
      provision intervals for these procedures, common validation assessments, typical
      follow-up care schedules, and source(s) of CI training. In addition, this study
      sought to evaluate if training and/or follow-up care differed between small and
      large CI centers. RESEARCH DESIGN: A cross-sectional survey design was used.
      STUDY SAMPLE: Target population included practicing audiologists working with
      pediatric CI users throughout the United States. Participation was voluntary,
      thus random selection could not be used. A total of 167 participants opened and
      began the online survey and 113 successfully completed the survey instrument
      (23.99% return rate). DATA COLLECTION AND ANALYSIS: Potential participants were
      identified using the "find a clinic" function on three CI manufacturers'
      websites. Potential participants were asked to complete an online survey seeking
      information about practices they employ in their clinical setting. Survey
      responses were analyzed for trends. RESULTS: Overall, a common follow-up schedule
      was determined, which included an average of 6.8 appointments within the first
      year. Minor differences in training and programming practices between small and
      large CI centers emerged; however, no statistically significant results were
      noted. Results did reveal trends in the use of certain clinical practices. This
      was particularly evident in the limited use of objective measures. CONCLUSIONS:
      Overall, the findings support other recent studies that suggest the development
      of CI guidelines that may standardize programming and follow-up practices of CI
      audiologists. This could prove valuable for the continual improvement of CI
      outcomes, particularly in the pediatric population.

PMID- 30222543
TI  - Listening Effort: Order Effects and Core Executive Functions.
AB  - BACKGROUND: Listening effort seems to depend on input-related listening demands
      and several factors internal to the individual listener. Input-related demands
      may be listening in noise compared with listening in quiet, and internal factors
      may be cognitive functions. PURPOSE: The purpose was to apply measures of
      listening effort and perceived listening effort in participants with normal
      hearing, to determine if there are any presentation order effects, and to explore
      the relationship between listening effort measured as accuracy, response times,
      efficiency of information encoding into long-term memory, perceived listening
      effort, and core executive functions. RESEARCH DESIGN: A within-subject design
      with repeated measures was used and a study of relationships between variables
      was made. STUDY SAMPLE: Thirty-two healthy adults with normal hearing. DATA
      COLLECTION AND ANALYSIS: Participants were tested individually by a listening
      task using a dual-task paradigm. The listening task was performed in quiet and in
      multitalker babble noise at 10 dB signal-to-noise ratio (SNR). Perceived
      listening effort and core executive functions (working memory, inhibitory
      control, and cognitive flexibility) were also assessed. RESULTS: The measures of
      listening effort (correct responses, response times, and immediate and delayed
      listening comprehension) failed to demonstrate increased listening effort in
      multitalker babble noise (10 dB SNR) compared with quiet, although a significant
      test order effect was seen for correct responses indicating that participants who
      first listened in noise did not improve in quiet. Perceived listening effort
      increased significantly in noise compared with quiet. No relationship was found
      between measures of listening effort and ratings of perceived listening effort.
      Working memory and cognitive flexibility were not related to ratings of perceived
      listening effort. In contrast, better inhibitory control was related to higher
      ratings in both quiet and in noise. CONCLUSIONS: It is possible that the SNR and
      measures used were not as sensitive as required to measure listening effort
      behaviorally. In the present experimental setup, prior noise exposure impedes the
      beneficial effects of performing a task in quiet. Self-reports seem to provide a
      valid measure of perceived listening effort that is related to the individual's
      inhibitory control. The present findings suggest that participants with better
      inhibitory control are more susceptible to the task demand level both in quiet
      and in noise.

PMID- 30222544
TI  - Transient Otoacoustic Emissions and Auditory Brainstem Responses in Low-Risk
      Cohort of Newborn and One-Month-Old Infants: Assessment of Infant Auditory System
      Physiology in the Prenatal Alcohol in SIDS and Stillbirth Network Safe Passage
      Study.
AB  - BACKGROUND: The Prenatal Alcohol and Sudden Infant Death Syndrome and Stillbirth
      Network, known as the "Safe Passage Study," enrolled approximately 12,000
      pregnant women from the United States and South Africa and followed the
      development of their babies through pregnancy and the infant's first year of life
      to investigate the role of prenatal alcohol exposure in the risk for sudden
      infant death syndrome (SIDS) and adverse pregnancy outcomes, such as stillbirth
      and fetal alcohol spectrum disorders. PURPOSE: Auditory system tests were
      included in the physiologic test battery used to study the effects of prenatal
      alcohol exposure on neurophysiology and neurodevelopment, as well as potential
      causal relationships between neurodevelopmental disorders and SIDS and/or
      stillbirth. The purpose of this manuscript is to describe normative results when
      using the auditory test battery applied. RESEARCH DESIGN: The test battery
      included the auditory brainstem response (ABR) and transient-evoked otoacoustic
      emissions (TEOAEs). Data were collected on individual ears of newborns and 1
      month-old infants. STUDY SAMPLE: From a cohort of 6,070 with auditory system
      exams, a normative subsample of 325 infants were selected who were not exposed
      prenatally to alcohol, cigarette smoke, or drugs nor were they preterm or low
      birthweight. The subsample is small relative to the overall study because of
      strict criteria for no exposure to substances known to be associated with SIDS or
      stillbirth and the exclusion of preterm and low birthweight infants. Expectant
      mothers were recruited from general maternity at two comprehensive clinical
      sites, in the northern plains in the United States and in Cape Town, South
      Africa. These populations were selected for study because both were known to be
      at high-risk for SIDS and stillbirth. DATA COLLECTION AND ANALYSIS: ABR and TEOAE
      recordings were stored electronically. Peak latency and amplitude analysis of
      ABRs were determined by study personnel, and results were evaluated for
      differences by age, sex, test site, race, and ear (left versus right). RESULTS:
      TEOAE findings were consistent with existing literature including the increase in
      signal-to-noise (SNR) over the first month of life. The SNR increase is due to an
      increase in amplitude of the emission. TEOAE amplitude asymmetry favoring the
      right ear was found, whereas SNR asymmetry was not, perhaps because of the small
      sample size. A nonsignificant trend toward larger responses in female babies was
      found; a result that is generally statistically significant in studies with
      larger samples. Latencies were found to be shorter in ABRs elicited in the right
      ear with amplitudes that were slightly bigger on average. An expected decrease in
      wave V latency was observed from birth to 1-month of age, but the finding was of
      borderline significance (p = 0.058). CONCLUSIONS: One month is a short time to
      judge development of the auditory system; however, the ABR and TEOAE findings
      were consistent with current literature. We conclude that the auditory system
      data acquired for the Safe Passage Study, as reflected in the data obtained from
      this cohort of "unexposed" infants, is consistent with published reports of these
      auditory system measures in the general population.

PMID- 30222545
TI  - The Characteristics of Adults with Severe Hearing Loss.
AB  - BACKGROUND: Severe hearing loss impairs communication in a wide range of
      listening environments. However, we lack data as to the specific objective and
      subjective abilities of listeners with severe hearing loss. Insight into those
      abilities may inform treatment choices. PURPOSE: The primary goal was to describe
      the audiometric profiles, spectral resolution ability, and objective and
      subjective speech perception of a sample of adult listeners with severe hearing
      loss, and to consider the relationships among those measures. We also considered
      the typical fitting received by individuals with severe loss, in terms of hearing
      aid style, electroacoustic characteristics, and features, as well as
      supplementary device use. RESEARCH DESIGN: A within-subjects design was used.
      STUDY SAMPLE: Participants included 36 adults aged 54-93 yr with unilateral or
      bilateral severe hearing loss. DATA COLLECTION AND ANALYSIS: Testing included a
      full hearing and hearing aid history; audiometric evaluation; loudness growth and
      dynamic range; spectral resolution; assessment of cochlear dead regions;
      objective and subjective assessment of speech recognition; and electroacoustic
      evaluation of current hearing aids. Regression models were used to analyze
      relationships between hearing loss, spectral resolution, and speech recognition.
      RESULTS: For speech in quiet, 60% of the variance was approximately equally
      accounted for by amount of hearing loss, spectral resolution, and number of dead
      regions. For speech in noise, only a modest proportion of performance variance
      was explained by amount of hearing loss. In general, participants were wearing
      amplification of appropriate style and technology for their hearing loss, but the
      extent of assistive technology use was low. Subjective communication ratings
      depended on the listening situation, but in general, were similar to previously
      published data for adults with mild-to-moderate loss who did not wear hearing
      aids. CONCLUSIONS: The present data suggest that the range of abilities of an
      individual can be more fully captured with comprehensive testing. Such testing
      also offers an opportunity for informed counseling regarding realistic
      expectations for hearing aid use and the availability of hearing assistive
      technology.

PMID- 30222547
TI  - A New Modeling Method to Characterize the Stance Control Function of Prosthetic
      Knee Joints.
AB  - OBJECTIVE: Biomechanical models can inform design and optimization of prosthetic
      devices by connecting empirically-derived biomechanical data to device design
      parameters. A new method is presented to characterize the function of prosthetic
      stance control under mobility conditions associated with activities of daily
      living. The method is based on a model of the gait modes corresponding to finite
      stance control states. METHODS: Empirical data from amputee and simulated gait
      were acquired using a custom built wearable instrument and input into the model.
      RESULTS: The modeling approach was shown to be robust, responsive and capable of
      accurate characterization of controller function under diverse of locomotor and
      prosthetic setup conditions. CONCLUSION: Future work is focused on the
      development of a fully self-contained wearable system, to facilitate collection
      of large data sets across a variety of user demographics, controller designs, and
      activities of daily living. SIGNIFICANCE: The method offers predictive
      capability, which can assist in the virtual testing of new designs or
      modifications.

PMID- 30222548
TI  - Joint Classification and Regression via Deep Multi-Task Multi-Channel Learning
      for Alzheimer's Disease Diagnosis.
AB  - In the field of computer-aided Alzheimer's disease (AD) diagnosis, jointly
      identifying brain diseases and predicting clinical scores using magnetic
      resonance (MR) imaging have attracted increasing attention since these two tasks
      are highly correlated. Most of existing joint learning approaches require hand
      crafted feature representations for MR images. Since handcrafted features of MRI
      and classification/regression models may not coordinate well with each other,
      conventional methods may lead to sub-optimal learning performance. Also,
      demographic information (e.g., age, gender, and education) of subjects may also
      be related to brain status, and thus can help improve the diagnostic performance.
      However, conventional joint learning methods seldom incorporate such demographic
      information into the learning models. To this end, we propose a deep multi-task
      multichannel learning ($DM^{2}L$) framework for simultaneous brain disease
      classification and clinical score regression, using MR imaging data and
      demographic information of subjects. Specifically, we first identify the
      discriminative anatomical landmarks from MR images in a data-driven manner, and
      then extract multiple image patches around these detected landmarks. We then
      propose a deep multi-task multi-channel convolutional neural network for joint
      classification and regression. Our $DM^{2}L$ framework can not only automatically
      learn discriminative features for MR images, but also explicitly incorporate the
      demographic information of subjects into the learning process. We evaluate the
      proposed method on four large multi-center cohorts with 1; 984 subjects, and the
      experimental results demonstrate that $DM^{2}L$ is superior to several state-of
      the-art joint learning methods in both the tasks of disease classification and
      clinical score regression.

PMID- 30222549
TI  - Full Modeling of High-Intensity Focused Ultrasound and Thermal Heating in the
      Kidney Using Realistic Patient Models.
AB  - OBJECTIVE: High-intensity focused ultrasound (HIFU) therapy can be used for
      noninvasive treatment of kidney (renal) cancer, but the clinical outcomes have
      been variable. In this study, the efficacy of renal HIFU therapy was studied
      using a nonlinear acoustic and thermal simulations in three patients. METHODS:
      The acoustic simulations were conducted with and without refraction in order to
      investigate its effect on the shape, size, and pressure distribution at the
      focus. The values for the attenuation, sound speed, perfusion, and thermal
      conductivity of the kidney were varied over the reported ranges to determine the
      effect of variability on heating. Furthermore, the phase aberration was studied
      in order to quantify the underlying phase shifts using a second order polynomial
      function. RESULTS: The ultrasound field intensity was found to drop on average
      11.1 dB with refraction and 6.4 dB without refraction. Reflection at tissue
      interfaces was found to result in a loss less than 0.1 dB. Focal point splitting
      due to refraction significantly reduced the heating efficacy. Perfusion did not
      have a large effect on heating during short sonication durations. Small changes
      in temperature were seen with varying attenuation and thermal conductivity, but
      no visible changes were present with sound speed variations. The aberration study
      revealed an underlying trend in the spatial distribution of the phase shifts.
      CONCLUSION: The results show that the efficacy of HIFU therapy in the kidney
      could be improved with aberration correction. SIGNIFICANCE: A method is proposed
      by that patient specific pre-treatment calculations could be used to overcome the
      aberration and therefore make ultrasound treatment possible.

PMID- 30222550
TI  - Motion Segmentation via Generalized Curvatures.
AB  - New depth sensors, like the Microsoft Kinect, produce streams of human pose data.
      These discrete pose streams can be viewed as noisy samples of an underlying
      continuous ideal curve that describes a trajectory through high-dimensional pose
      space. This paper introduces a technique for generalized curvature analysis (GCA)
      that determines features along the trajectory which can be used to characterize
      change and segment motion. Tools are developed for approximating generalized
      curvatures at mean points along a curve in terms of the singular values of local
      mean-centered data balls. The features of the GCA algorithm are illustrated on
      both synthetic and real examples, including data collected from a Kinect II
      sensor. We also applied GCA to the Carnegie Mellon University Motion Capture
      (MoCaP) database. Given that GCA scales linearly with the length of the time
      series we are able to analyze large data sets without down sampling. It is
      demonstrated that the generalized curvature approximations can be used to segment
      pose streams into motions and transitions between motions. The GCA algorithm can
      identify 94.2% of the transitions between motions without knowing the set of
      possible motions in advance, even though the subjects do not stop or pause
      between motions.

PMID- 30222551
TI  - Segmentation of Laser Point Clouds in Urban Areas by a Modified Normalized Cut
      Method.
AB  - Normalized Cut is a well-established divisive image segmentation method, which we
      adapt in this paper for the segmentation of laser point clouds in urban areas.
      Our focus is on polyhedral objects with planar surfaces. Due to its target
      function, Normalized Cut favours cuts with "short cut lines" or "small cut
      surfaces", which is a drawback for our application. We therefore modify the
      target function, weighting the similarity measures with distance-dependent
      weights. We call the induced minimization problem "Distance-weighted Cut"
      (DWCut). The new target function leads to a generalized eigenvalue problem, which
      is slightly more complicated than the corresponding problem for the Normalized
      Cut; on the other hand, the new target function is easier to interpret and avoids
      some drawbacks of the Normalized Cut. We point out an efficient method for the
      numerical solution of the eigenvalue problem which is based on a Krylov subspace
      method. DWCut can be beneficially combined with an aggregation in order to reduce
      the computational effort and to avoid shortcomings due to insufficient plane
      parameters.

PMID- 30222552
TI  - Material Classification from Time-of-Flight Distortions.
AB  - This paper presents a material classification method using an off-the-shelf Time
      of-Flight (ToF) camera. The proposed method is built upon a key observation that
      the depth measurement by a ToF camera is distorted for objects with certain
      materials, especially with translucent materials. We show that this distortion is
      due to the variation of time domain impulse responses across materials and also
      due to the measurement mechanism of the ToF cameras. Specifically, we reveal that
      the amount of distortion varies according to the modulation frequency of the ToF
      camera, the object material, and the distance between the camera and object. Our
      method uses the depth distortion of ToF measurements as a feature for
      classification and achieves material classification of a scene. Effectiveness of
      the proposed method is demonstrated by numerical evaluations and real-world
      experiments, showing its capability of material classification, even for visually
      indistinguishable objects.

PMID- 30222553
TI  - High Temporal-Resolution Dynamic PET Image Reconstruction Using a New
      Spatiotemporal Kernel Method.
AB  - Current clinical dynamic PET has an effective temporal resolution of 5-10
      seconds, which can be adequate for traditional compartmental modeling but is
      inadequate for exploiting the benefit of more advanced tracer kinetic modeling
      for characterization of diseases (e.g., cancer and heart disease). There is a
      need to improve dynamic PET to allow fine temporal sampling of 1-2 seconds.
      However, reconstruction of these shorttime frames from tomographic data is
      extremely challenging as the count level of each frame is very low and high noise
      presents in both spatial and temporal domains. Previously the kernel framework
      has been developed and demonstrated as a statistically efficient approach to
      utilizing image prior for lowcount PET image reconstruction. Nevertheless, the
      existing kernel methods mainly explore spatial correlations in the data and only
      have a limited ability in suppressing temporal noise. In this paper, we propose a
      new kernel method which extends the previous spatial kernel method to the general
      spatiotemporal domain. The new kernelized model encodes both spatial and temporal
      correlations obtained from image prior information and is incorporated into the
      PET forward projection model to improve the maximum likelihood (ML) image
      reconstruction. Computer simulations and an application to real patient scan have
      shown that the proposed approach can achieve effective noise reduction in both
      spatial and temporal domains and outperform the spatial kernel method and
      conventional ML reconstruction method for improving high temporal-resolution
      dynamic PET imaging.

PMID- 30222554
TI  - Iterative PET Image Reconstruction Using Convolutional Neural Network
      Representation.
AB  - PET image reconstruction is challenging due to the ill-poseness of the inverse
      problem and limited number of detected photons. Recently deep neural networks
      have been widely and successfully used in computer vision tasks and attracted
      growing interests in medical imaging. In this work, we trained a deep residual
      convolutional neural network to improve PET image quality by using the existing
      inter-patient information. An innovative feature of the proposed method is that
      we embed the neural network in the iterative reconstruction framework for image
      representation, rather than using it as a post-processing tool. We formulate the
      objective function as a constrained optimization problem and solve it using the
      alternating direction method of multipliers (ADMM) algorithm. Both simulation
      data and hybrid real data are used to evaluate the proposed method.
      Quantification results show that our proposed iterative neural network method can
      outperform the neural network denoising and conventional penalized maximum
      likelihood methods.

PMID- 30222555
TI  - A dual-mode imaging catheter for intravascular ultrasound application.
AB  - Both the morphological anatomy and functional parameters such as flow speed of
      the artery provide valuable information for the evaluation of cardiovascular
      diseases. Direct measurement of the arterial wall can be achieved by
      intravascular optical/ultrasound imaging methods, however no functional data are
      acquired with these methods. Fractional flow reserve (FFR) and Doppler wire have
      been used to assess the blood flow information, but do not provide cross
      sectional images of the artery. This study is the first to design and fabricate a
      dual mode imaging catheter that contains a forward-looking ultrasonic transducer
      and a side-looking ultrasonic transducer together in one catheter. This dual-mode
      catheter not only provides morphological information about the artery, but also a
      precise measurement of functional flow. The data indicate that the proposed
      catheter can be used to acquire multiple parameters of the artery with a one-time
      procedure. This novel one-catheter approach could be used for the functional
      diagnosis of atherosclerotic arteries.

PMID- 30222556
TI  - Sensitivity Enhancement of MEMS Diaphragm Hydrophones Using an Integrated Ring
      MOSFET Transducer.
AB  - A high-sensitivity MEMS diaphragm hydrophone has been proposed. The designed
      hydrophone has a higher sensitivity in comparison with its previous counterparts.
      Readout electronics includes an integrated MOSFET and an external operational
      amplifier. An integrated ring MOSFET with a piezoelectric gate has been used as
      the strain to the electrical current transducer. The drain of the MOSFET has been
      connected to an operational amplifier that converts the transistor current to the
      voltage and also amplifies it. An analytical relation for the sensitivity has
      been derived which is in an outstanding agreement with the finite-element
      analysis. It has been proven that the changes in the channel length and mobility
      are negligible, and the transistor current is merely under the influence of the
      pressure-induced charges on the piezoelectric surface which directly produces the
      vertical electric field. It has been shown that the ring MOSFET transducer can
      help designing MEMS hydrophones with smaller dimensions while keeping the
      sensitivity as much as the larger structures.

PMID- 30222557
TI  - A Low-Cost Miniature Histotripsy Transducer for Precision Tissue Ablation.
AB  - A miniature, 10 mm aperture histotripsy transducer with an f-number of 0.7 was
      fabricated using an elliptically shaped aluminum lens, which was epoxy-bonded to
      an air-backed 5.0 MHz, PTZ-5A, 1-3 dice-and-fill piezoelectric composite, and the
      lens coupled to water using a quarter-wavelength matching layer of Parylene-C. A
      Krimholtz-Leedom-Matthaei model of the device and curved lens was developed. The
      epoxy layer resulted in an increased power output at 6.8 MHz compared to the 5
      MHz composite design. Cavitation was observed in water by driving the composite
      with a 173 V single-cycle, unipolar 6.8 MHz pulse at a pulse repetition frequency
      of 50 Hz, and a bubble cloud 264 long by 124 wide was measured. A coregistered
      imaging and ablation device was also fabricated and characterized. The
      coregistered device was modified to include a mm square hole through the center,
      allowing access for a high-frequency imaging array, and both imaging and ablation
      are demonstrated in cerebral tissue with this device. Radial -3 dB beam widths
      were measured as 0.145 and 0.116 mm, and axial -3 dB depths of field were 0.698
      and 0.752 mm for the noncoregistered and coregistered transducers, respectively.
      Total material cost for the transducer and pulser board is below $200 USD.

PMID- 30222558
TI  - Low Variance Estimation of Backscatter Quantitative Ultrasound Parameters Using
      Dynamic Programming.
AB  - One of the main limitations of ultrasound imaging is that image quality and
      interpretation depend on the skill of the user and the experience of the
      clinician. Quantitative ultrasound (QUS) methods provide objective, system
      independent estimates of tissue properties, such as acoustic attenuation and
      backscattering properties of tissue, which are valuable as objective tools for
      both diagnosis and intervention. Accurate and precise estimation of these
      properties requires correct compensation for intervening tissue attenuation.
      Prior attempts to estimate intervening-tissue attenuation based on minimizing
      cost functions that compared backscattered echo data to models have resulted in
      limited precision and accuracy. To overcome these limitations, in this paper, we
      incorporate the prior information of piecewise continuity of QUS parameters as a
      regularization term into our cost function. We further propose to calculate this
      cost function using dynamic programming (DP), a computationally efficient
      optimization algorithm that finds the global optimum. Our results on tissue
      mimicking phantoms show that DP substantially outperforms a published least
      squares method in terms of both estimation bias and variance.

PMID- 30222559
TI  - Autoregressive Signal Processing Applied to High-Frequency Acoustic Microscopy of
      Soft Tissues.
AB  - Quantitative acoustic microscopy (QAM) at frequencies exceeding 100 MHz has
      become an established imaging tool to depict acoustical and mechanical properties
      of soft biological tissues at microscopic resolutions. In this study, we
      investigate a novel autoregressive (AR) model to improve signal processing and
      parameter estimation and to test its applicability to QAM. The performance of the
      AR model for estimating acoustical parameters of soft tissues (i.e., acoustic
      impedance, speed of sound, and attenuation) was compared to the performance of
      the Hozumi model using simulated ultrasonic QAM signals and using experimentally
      measured signals from thin (i.e., 12 and ) sections of human lymph-node and pig
      cornea tissue specimens. Results showed that the AR and Hozumi methods performed
      equally well (i.e., produced an estimation error of 0) in signals with low,
      linear attenuation in the tissue and high impedance contrast between the tissue
      and the coupling medium. However, the AR model outperformed the Hozumi model in
      estimation accuracy and stability (i.e., parameter error variation and number of
      outliers) in cases of 1) thin tissue-sample thickness and high tissue-sample
      speed of sound, 2) small impedance contrast between the tissue sample and the
      coupling medium, 3) high attenuation in the tissue sample, and 4) nonlinear
      attenuation in the tissue sample. Furthermore, the AR model allows estimating the
      exponent of nonlinear attenuation. The results of this study suggest that the AR
      model approach can improve current QAM by providing more reliable, quantitative,
      tissue-property estimates and also provides additional values of parameters
      related to nonlinear attenuation.

PMID- 30222560
TI  - Muon Tracing and Image Reconstruction Algorithms for Cosmic Ray Muon Computed
      Tomography.
AB  - Cosmic ray muon-computed tomography (MUCT) is a new imaging modality with unique
      characteristics that could be particularly important for diverse applications
      including nuclear nonproliferation, spent nuclear fuel monitoring, cargo
      scanning, and volcano imaging. The strong scattering dependence of muons on
      atomic number Z in combination with high penetration range could offer a
      significant advantage over existing techniques when dense, shielded containers
      must be imaged. However, MUCT reconstruction using conventional filtered back
      projection is limited due to the overly simple assumptions that do not take into
      account the curved path caused by multiple Coulomb scattering prompting the need
      for more sophisticated approaches to be developed. In this paper, we argue that
      the use of improved muon tracing and scattering angle projection algorithms as
      well as an algebraic reconstruction technique should produce muon tomographic
      images with improved quality - or require fewer muons to produce the same image
      quality - compared to the case where conventional methods are used. We report on
      the development and assessment of three novel muon tracing methods and two
      scattering angle projection methods for MUCT. Simulated dry storage casks with
      single and partial missing fuel assemblies were used as numerical examples to
      assess and compare the proposed methods. The reconstructed images showed an
      expected improvement in image quality when compared with conventional techniques,
      even without muon momentum information, which should lead to improved detection
      capability, even for partial defects.

PMID- 30222561
TI  - Large-Scale Study of Perceptual Video Quality.
AB  - The great variations of videographic skills in videography, camera designs,
      compression and processing protocols, communication and bandwidth environments,
      and displays leads to an enormous variety of video impairments. Current
      noreference (NR) video quality models are unable to handle this diversity of
      distortions. This is true in part because available video quality assessment
      databases contain very limited content, fixed resolutions, were captured using a
      small number of camera devices by a few videographers and have been subjected to
      a modest number of distortions. As such, these databases fail to adequately
      represent real world videos, which contain very different kinds of content
      obtained under highly diverse imaging conditions and are subject to authentic,
      complex and often commingled distortions that are difficult or impossible to
      simulate. As a result, NR video quality predictors tested on real-world video
      data often perform poorly. Towards advancing NR video quality prediction, we have
      constructed a largescale video quality assessment database containing 585 videos
      of unique content, captured by a large number of users, with wide ranges of
      levels of complex, authentic distortions. We collected a large number of
      subjective video quality scores via crowdsourcing. A total of 4776 unique
      participants took part in the study, yielding more than 205000 opinion scores,
      resulting in an average of 240 recorded human opinions per video. We demonstrate
      the value of the new resource, which we call the LIVE Video Quality Challenge
      Database (LIVE-VQC for short), by conducting a comparison of leading NR video
      quality predictors on it. This study is the largest video quality assessment
      study ever conducted along several key dimensions: number of unique contents,
      capture devices, distortion types and combinations of distortions, study
      participants, and recorded subjective scores. The database is available for
      download on this link: http://live.ece.utexas.edu/research/LIVEVQC/index.html.

PMID- 30222562
TI  - Statistical Nearest Neighbors for Image Denoising.
AB  - Non-local-means image denoising is based on processing a set of neighbors for a
      given reference patch. few nearest neighbors (NN) can be used to limit the
      computational burden of the algorithm. Resorting to a toy problem, we show
      analytically that sampling neighbors with the NN approach introduces a bias in
      the denoised patch. We propose a different neighbors' collection criterion to
      alleviate this issue, which we name statistical NN (SNN). Our approach
      outperforms the traditional one in case of both white and colored noise: fewer
      SNNs can be used to generate images of superior quality, at a lower computational
      cost. A detailed investigation of our toy problem explains the differences
      between NN and SNN from a grounded point of view. The intuition behind SNN is
      quite general, and it leads to image quality improvement also in the case of
      bilateral filtering. The MATLAB code to replicate the results presented in the
      paper is freely available.

PMID- 30222563
TI  - Dual-Transfer Face Sketch-Photo Synthesis.
AB  - Recognizing the identity of a sketched face from a face photograph dataset is a
      critical yet challenging task in many applications, not least law enforcement and
      criminal investigations. An intelligent sketched face identification system would
      rely on automatic face sketch synthesis from photographs, thereby avoiding the
      cost of artists manually drawing sketches. However, conventional face sketch
      photo synthesis methods tend to generate sketches that are consistent with the
      artists'drawing styles. Identity-specific information is often overlooked,
      leading to unsatisfactory identity verification and recognition performance. In
      this paper, we discuss the reasons why conventional methods fail to recover
      identity-specific information. Then, we propose a novel dual-transfer face sketch
      photo synthesis framework composed of an inter-domain transfer process and an
      intra-domain transfer process. In the inter-domain transfer, a regressor of the
      test photograph with respect to the training photographs is learned and
      transferred to the sketch domain, ensuring the recovery of common facial
      structures during synthesis. In the intra-domain transfer, a mapping
      characterizing the relationship between photographs and sketches is learned and
      transferred across different identities, such that the loss of identity-specific
      information is suppressed during synthesis. The fusion of information recovered
      by the two processes is straightforward by virtue of an ad hoc information
      splitting strategy. We employ both linear and nonlinear formulations to
      instantiate the proposed framework. Experiments on The Chinese University of Hong
      Kong face sketch database demonstrate that compared to the current state-of-the
      art the proposed framework produces more identifiable facial structures and
      yields higher face recognition performance in both the photo and sketch domains.

PMID- 30222564
TI  - Hyperspectral Imagery Classification via Stochastic HHSVMs.
AB  - Hyperspectral imagery (HSI) has shown promising results in real-world
      applications. However, the technological evolution of optical sensors poses two
      main challenges in HSI classification: 1) the spectral band is usually redundant
      and noisy and 2) HSI with millions of pixels has become increasingly common in
      real-world applications. Motivated by the recent success of hybrid huberized
      support vector machines (HHSVMs), which inherit the benefits of both lasso and
      ridge regression, this paper first investigates the advantages of HHSVM for HSI
      applications. Unfortunately, the existing HHSVM solvers suffer from prohibitive
      computational costs on large-scale data sets. To solve this problem, this paper
      proposes simple and effective stochastic HHSVM algorithms for HSI classification.
      In the stochastic settings, we show that with a probability of at least , our
      algorithms find an -accurate solution using iterations. Since the convergence
      rate of our algorithms does not depend on the size of the training set, our
      algorithms are suitable for handling large-scale problems. We demonstrate the
      superiority of our algorithms by conducting experiments on large-scale binary and
      multiclass classification problems, comparing to the state-of-the-art HHSVM
      solvers. Finally, we apply our algorithms to real HSI classification and achieve
      promising results.

PMID- 30222565
TI  - Gated-GAN: Adversarial Gated Networks for Multi-Collection Style Transfer.
AB  - Style transfer describes the rendering of an image's semantic content as
      different artistic styles. Recently, generative adversarial networks (GANs) have
      emerged as an effective approach in style transfer by adversarially training the
      generator to synthesize convincing counterfeits. However, traditional GAN suffers
      from the mode collapse issue, resulting in unstable training and making style
      transfer quality difficult to guarantee. In addition, the GAN generator is only
      compatible with one style, so a series of GANs must be trained to provide users
      with choices to transfer more than one kind of style. In this paper, we focus on
      tackling these challenges and limitations to improve style transfer. We propose
      adversarial gated networks (Gated-GAN) to transfer multiple styles in a single
      model. The generative networks have three modules: an encoder, a gated
      transformer, and a decoder. Different styles can be achieved by passing input
      images through different branches of the gated transformer. To stabilize
      training, the encoder and decoder are combined as an auto-encoder to reconstruct
      the input images. The discriminative networks are used to distinguish whether the
      input image is a stylized or genuine image. An auxiliary classifier is used to
      recognize the style categories of transferred images, thereby helping the
      generative networks generate images in multiple styles. In addition, Gated-GAN
      makes it possible to explore a new style by investigating styles learned from
      artists or genres. Our extensive experiments demonstrate the stability and
      effectiveness of the proposed model for multi-style transfer.

PMID- 30222566
TI  - Triple Verification Network for Generalised Zero-shot Learning.
AB  - Conventional Zero-shot Learning approaches often suffer from severe performance
      degradation in the Generalised Zero-shot Learning (GZSL) scenario, i.e. to
      recognise test images that are from both seen and unseen classes. This paper
      studies the Class-level Over-fitting (CO) and empirically shows its effects to
      GZSL. We then address ZSL as a Triple Verification problem and propose a unified
      optimisation of regression and compatibility functions, i.e. two main streams of
      existing ZSL approaches. The complementary losses mutually regularise the same
      model to mitigate the CO problem. Furthermore, we implement a deep extension
      paradigm to linear models and significantly outperforms state-of-the-art methods
      in both GZSL and ZSL scenarios on the four standard benchmarks.

PMID- 30222567
TI  - Cross-Scale Predictive Dictionaries.
AB  - Sparse representations using data dictionaries provide an efficient model
      particularly for signals that do not enjoy alternate analytic sparsifying
      transformations. However, solving inverse problems with sparsifying dictionaries
      can be computationally expensive, especially when the dictionary under
      consideration has a large number of atoms. In this paper, we incorporate
      additional structure on to dictionary-based sparse representations for visual
      signals to enable speedups when solving sparse approximation problems. The
      specific structure that we endow onto sparse models is that of a multi-scale
      modeling where the sparse representation at each scale is constrained by the
      sparse representation at coarser scales. We show that this cross-scale predictive
      model delivers significant speedups, often in the range of , with little loss in
      accuracy for linear inverse problems associated with images, videos, and light
      fields.

PMID- 30222568
TI  - Interpreting and Extending the Guided Filter via Cyclic Coordinate Descent.
AB  - The guided filter (GF) is a widely used smoothing tool in computer vision and
      image processing. However, to the best of our knowledge, few papers investigate
      the mathematical connection between this filter and the least-squares
      optimization. In this paper, we first interpret the guided filter as the cyclic
      coordinate descent (CCD) solver of a least-squares objective function. This
      discovery implies an extension approach to generalize the guided filter since we
      can change the least-squares objective function and define new filters as the
      first pass iteration of the CCD solver of modified objective functions. In
      addition, referring to the iterative minimizing procedure of the CCD, we can
      derive new rolling filtering schemes. So, we are reasonable to say that our
      discovery not only reveals an approach to design new GF-like filters adapting to
      specific requirements of applications but also offers thorough explanations for
      two rolling filtering schemes of the guided filter as well as the method to
      extend them. Experiments prove our new proposed filters and rolling filtering
      schemes could produce state-of-the-art results.

PMID- 30222569
TI  - Extracting Privileged Information for Enhancing Classifier Learning.
AB  - The accuracy of data-driven learning approaches is often unsatisfactory when the
      training data is inadequate either in quantity or quality. Manually labeled
      privileged information (PI), e.g., attributes, tags or properties, is usually
      incorporated to improve classifier learning. However, the process of manually
      labeling is time-consuming and labor-intensive. Moreover, due to the limitations
      of personal knowledge, manually labeled PI may not be rich enough. To address
      these issues, we propose to enhance classifier learning by exploring PI from
      untagged corpora, which can effectively eliminate the dependency on manually
      labeled data and obtain much richer PI. In detail, we treat each selected PI as a
      subcategory and learn one classifier for each subcategory independently. The
      classifiers for all subcategories are integrated together to form a more powerful
      category classifier. Particularly, we propose a novel instancelevel multi
      instance learning (MIL) model to simultaneously select a subset of training
      images from each subcategory and learn the optimal SVM classifiers based on the
      selected images. Extensive experiments on four benchmark datasets demonstrate the
      superiority of our proposed approach.

PMID- 30222570
TI  - D3R-Net: Dynamic Routing Residue Recurrent Network for Video Rain Removal.
AB  - In this paper, we address the problem of video rain removal by considering rain
      occlusion regions, i.e., very low light transmittance for rain streaks. Different
      from additive rain streaks, in such occlusion regions, the details of backgrounds
      are completely lost. Therefore, we propose a hybrid rain model to depict both
      rain streaks and occlusions. Integrating the hybrid model and useful motion
      segmentation context information, we present a Dynamic Routing Residue Recurrent
      Network (D3R-Net). D3R-Net first extracts the spatial features by a residual
      network. Then, the spatial features are aggregated by recurrent units along the
      temporal axis. In the temporal fusion, the context information is embedded into
      the network in a "dynamic routing" way. A heap of recurrent units takes
      responsibility for handling the temporal fusion in given contexts, e.g., rain or
      non-rain regions. In the certain forward and backward processes, one of these
      recurrent units is mainly activated. Then, a context selection gate is employed
      to detect the context and select one of these temporally fused features generated
      by these recurrent units as the final fused feature. Finally, this last feature
      plays a role of "residual feature." It is combined with the spatial feature and
      then used to reconstruct the negative rain streaks. In such a D3R-Net, we
      incorporate motion segmentation, which denotes whether a pixel belongs to fast
      moving edges or not, and rain type indicator, indicating whether a pixel belongs
      to rain streaks, rain occlusions, and non-rain regions, as the context variables.
      Extensive experiments on a series of synthetic and real videos with rain streaks
      verify not only the superiority of the proposed method over state of the art but
      also the effectiveness of our network design and its each component.

PMID- 30222571
TI  - Image Estimation in the Presence of Irregular Sampling, Noise, and Pointing
      Jitter.
AB  - We consider an acquisition system where a continuous image is reconstructed from
      a set of irregularly distributed noisy samples. Moreover, the system is affected
      by a random pointing jitter which makes the actual sampling positions different
      from the nominal ones. We develop a model for the system and derive the optimal,
      minimum variance unbiased (MVU) estimate. Unfortunately, the latter estimate is
      not practical to compute when the data size is large. Therefore, we develop a
      simplified, low resolution model and derive the corresponding MVU estimate, which
      has a drastically lower complexity. Moreover, we analyze the estimators'
      performance by using both theoretical analysis and simulations. Finally, we
      discuss the application to the data of the Photodetector Array Camera and
      Spectrometer (PACS) instrument, which is an infrared photometer on board the
      Herschel satellite.

PMID- 30222572
TI  - A Convergent Image Fusion Algorithm Using Scene-Adapted Gaussian-Mixture-Based
      Denoising.
AB  - We propose a new approach to image fusion, inspired by the recent plug-and-play
      (PnP) framework. In PnP, a denoiser is treated as a black-box and plugged into an
      iterative algorithm, taking the place of the proximity operator of some convex
      regularizer, which is formally equivalent to a denoising operation. This approach
      offers flexibility and excellent performance, but convergence may be hard to
      analyze, as most state-of-the-art denoisers lack an explicit underlying objective
      function. Here, we propose using a scene-adapted denoiser (i.e., targeted to the
      specific scene being imaged) plugged into the iterations of the alternating
      direction method of multipliers (ADMM). This approach, which is a natural choice
      for image fusion problems, not only yields state-of-the-art results, but it also
      allows proving convergence of the resulting algorithm. The proposed method is
      tested on two different problems: hyperspectral fusion/sharpening and fusion of
      blurred-noisy image pairs.

PMID- 30222573
TI  - RegressionExplorer: Interactive Exploration of Logistic Regression Models with
      Subgroup Analysis.
AB  - We present RegressionExplorer, a Visual Analytics tool for the interactive
      exploration of logistic regression models. Our application domain is Clinical
      Biostatistics, where models are derived from patient data with the aim to obtain
      clinically meaningful insights and consequences. Development and interpretation
      of a proper model requires domain expertise and insight into model
      characteristics. Because of time constraints, often a limited number of candidate
      models is evaluated. RegressionExplorer enables experts to quickly generate,
      evaluate, and compare many different models, taking the workflow for model
      development as starting point. Global patterns in parameter values of candidate
      models can be explored effectively. In addition, experts are enabled to compare
      candidate models across multiple subpopulations. The insights obtained can be
      used to formulate new hypotheses or to steer model development. The effectiveness
      of the tool is demonstrated for two uses cases: prediction of a cardiac
      conduction disorder in patients after receiving a heart valve implant and
      prediction of hypernatremia in critically ill patients.

PMID- 30222574
TI  - Narrative and Spatial Memory for Jury Viewings in a Reconstructed Virtual
      Environment.
AB  - This paper showcases one way of how virtual reconstruction can be used in a
      courtroom. The results of a pilot study on narrative and spatial memory are
      presented in the context of viewing real and virtual copies of a simulated crime
      scene. Based on current court procedures, three different viewing options were
      compared: photographs, a real life visit, and a 3D virtual reconstruction of the
      scene viewed in a Virtual Reality headset. Participants were also given a written
      narrative that included the spatial locations of stolen goods and were measured
      on their ability to recall and understand these spatial relationships of those
      stolen items. The results suggest that Virtual Reality is more reliable for
      spatial memory compared to photographs and that Virtual Reality provides a
      compromise for when physical viewing of crime scenes are not possible. We
      conclude that Virtual Reality is a promising medium for the court.

PMID- 30222575
TI  - PANENE: A Progressive Algorithm for Indexing and Querying Approximate k-Nearest
      Neighbors.
AB  - We present PANENE, a progressive algorithm for approximate nearest neighbor
      indexing and querying. Although the use of k-nearest neighbor (KNN) libraries is
      common in many data analysis methods, most KNN algorithms can only be queried
      when the whole dataset has been indexed, i.e., they are not online. Even the few
      online implementations are not progressive in the sense that the time to index
      incoming data is not bounded and cannot satisfy the latency requirements of
      progressive systems. This long latency has significantly limited the use of many
      machine learning methods, such as t-SNE, in interactive visual analytics. PANENE
      is a novel algorithm for Progressive Approximate k-NEarest NEighbors, enabling
      fast KNN queries while continuously indexing new batches of data. Following the
      progressive computation paradigm, PANENE operations can be bounded in time,
      allowing analysts to access running results within an interactive latency. PANENE
      can also incrementally build and maintain a cache data structure, a KNN lookup
      table, to enable constant-time lookups for KNN queries. Finally, we present three
      progressive applications of PANENE, such as regression, density estimation, and
      responsive t-SNE, opening up new opportunities to use complex algorithms in
      interactive systems.

PMID- 30222577
TI  - Realistic Procedural Plant Modeling from Multiple View Images.
AB  - In this paper, we describe a novel procedural modeling technique for generating
      realistic plant models from multi-view photographs. The realism is enhanced via
      visual and spatial information acquired from images. In contrast to previous
      approaches that heavily rely on user interaction to segment plants or recover
      branches in images, our method automatically estimates an accurate depth map of
      each image and extracts a 3D dense point cloud by exploiting an efficient
      stereophotogrammetry approach. Taking this point cloud as a soft constraint, we
      fit a parametric plant representation to simulate the plant growth progress. In
      this way, we are able to combine real data (photos and 3D point clouds) analysis
      with rule-based procedural plant modeling. We demonstrate the robustness of the
      proposed approach by modeling a variety of plants with complex branching
      structures and significant self-occlusions. We also demonstrate that the proposed
      framework can be used to reconstruct ground-covering plants, such as bushes and
      shrubs which have gained little attention in the literature. The effectiveness of
      our approach is validated by visually and quantitatively comparing with the state
      of-the-art approaches.

PMID- 30222576
TI  - The Effect of Focal Distance, Age, and Brightness on Near-Field Augmented Reality
      Depth Matching.
AB  - Many augmented reality (AR) applications operate within near-field reaching
      distances, and require matching the depth of a virtual object with a real object.
      The accuracy of this matching was measured in three experiments, which examined
      the effect of focal distance, age, and brightness, within distances of 33.3 to
      50~cm, using a custom-built AR haploscope. Experiment~I examined the effect of
      focal demand, at the levels of collimated (infinite focal distance), consistent
      with other depth cues, and at the midpoint of reaching distance. Observers were
      too young to exhibit age-related reductions in accommodative ability. The depth
      matches of collimated targets were increasingly overestimated with increasing
      distance, consistent targets were slightly underestimated, and midpoint targets
      were accurately estimated. Experiment~II replicated Experiment~I, with older
      observers. Results were similar to Experiment~I. Experiment~III replicated
      Experiment~I with dimmer targets, using young observers. Results were again
      consistent with Experiment~I, except that both consistent and midpoint targets
      were accurately estimated. In all cases, collimated results were explained by a
      model, where the collimation biases the eyes' vergence angle outwards by a
      constant amount. Focal demand and brightness affect near-field AR depth matching,
      while age-related reductions in accommodative ability have no effect.

PMID- 30222578
TI  - Assigning Rated Items to Locations in non-list Display Layouts.
AB  - One of the most common ways in which results are displayed by an information
      retrieval system is in the form of a list, in which the most relevant results
      appear in the first positions. Today's large screens, however, allow one to
      create more complex displays of results, especially in cases such as image
      retrieval, in which each unit returned is fairly compact. For these layouts the
      simple list model is no longer valid, since the relations between the slots in
      which the results are placed do not form a sequence, that is, the relation among
      them is no longer that of a total order. In this paper we model these layouts as
      partial orders and show that a ?dqt{perfect display} property can be obtained
      only in the case of lists. For the other layouts, we define two classes of
      representation functions: ?dqt{safe} functions (which display results without
      adding spurious structure) and ?dqt{rich} functions (which do not drop any
      structure from the result set), as well as an algorithm to optimally display
      fully ordered result sets in arbitrary display layouts.

PMID- 30222579
TI  - Somatosensory Evoked Responses Elicited by Haptic Sensations in Midair.
AB  - The design of human-machine interfaces (HMIs) by virtual haptics is an emerging
      field of research. So far, the perception of virtual haptic feedback, e.g.,
      generated by focused ultrasound in midair has not been objectively evaluated.
      This paper demonstrates the feasibility of eliciting somatosensory evoked
      potentials (SEPs) with ultrasonic stimuli in midair for the first time. The palm
      was stimulated by short ultrasonic focal points generated by an ultrasound board.
      The results are compared with a no stimulation condition as well as with the
      results of a vibro tactile stimulation. The SEPs are analyzed with the wavelet
      phase synchronization stability (WPSS) and the M-consecutive averaged WPSS. The
      results indicate a clear SEP waveform elicited by ultrasound. It can be
      significantly differentiated from a no stimulation condition by the M-consecutive
      averaged WPSS. These results could enable the possibility of developing an
      objective evaluation method for virtual haptic feedback in HMIs.

PMID- 30222580
TI  - Preprocessing Sequence Coverage Data for Precise Detection of Copy Number
      Variations.
AB  - Copy number variation (CNV) is a type of genomic/genetic variation that plays an
      important role in phenotypic diversity, evolution, and disease susceptibility.
      Next generation sequencing (NGS) technologies have created an opportunity for
      more accurate detection of CNVs with higher resolution. However, efficient and
      precise detection of CNVs remains challenging due to high levels of noise and
      biases, data heterogeneity and the "big data" nature of NGS data. Sequence
      coverage (readcount) data are mostly used for detecting CNVs, specially for whole
      exome sequencing data. Readcount data are contaminated with several types of
      biases and noise that hinder accurate detection of CNVs. In this work, we
      introduce a novel preprocessing pipeline for reducing noise and biases to improve
      the detection accuracy of CNVs in heterogeneous NGS data, such as cancer whole
      exome sequencing data. We have employed several normalization methods to reduce
      readcount's biases that are due to GC content of reads, read alignment problems,
      and sample impurity. We have also developed a novel efficient and effective
      smoothing approach based on Taut String to reduce noise and increase CNV
      detection power. Using simulated and real data we showed that employing the
      proposed preprocessing pipeline significantly improves the accuracy of CNV
      detection.

PMID- 30222581
TI  - Bounded Fuzzy Possibilistic Method reveals information about lung cancer through
      analysis of metabolomics.
AB  - Learning methods, such as conventional clustering and classification, have been
      applied in diagnosing diseases to categorize samples based on their features.
      Going beyond clustering samples, membership degrees represent to what degree each
      sample belongs to a cluster. Variation of membership degrees in each cluster
      provides information about the cluster as a whole and each sample individually
      which enables to have insights toward precision medicine. Membership degrees are
      measured more accurately through removing restrictions from clustering samples.
      Bounded Fuzzy Possibilistic Method (BFPM) introduces a membership function that
      keeps the search space flexible to cluster samples with higher accuracy. The
      method evaluates samples for their movement from one cluster to another. This
      technique allows us to find critical samples in advance those with potential
      ability to belong to other clusters in the near future. BFPM was applied on
      metabolomics of individuals in a lung cancer case-control study. Metabolomics as
      proximal molecular signals to the actual disease processes may serve as strong
      biomarkers of current disease process. The goal is to know whether serum
      metabolites of healthy human can be differentiated from those with lung cancer.
      Using BFPM, some differences were observed, the pathology data were evaluated,
      and critical samples were recognized.

PMID- 30222582
TI  - A Gaussian Mixture-Model Exploiting Pathway Knowledge for Dissecting Cancer
      Heterogeneity.
AB  - In this work, we develop a systematic approach for applying pathway knowledge to
      a multivariate Gaussian mixture model for dissecting a heterogeneous cancer
      tissue. The downstream transcription factors are selected as observables from
      available partial pathway knowledge in such a way that the subpopulations produce
      some differential behavior in response to the drugs selected in the upstream. For
      each subpopulation, each unique (drug, observable) pair is considered as a unique
      dimension of a multivariate Gaussian distribution. Expectation-maximization (EM)
      algorithm with hill-climbing is then used to rank the most probable estimates of
      the mixture composition based on the log-likelihood value. A major contribution
      of this work is to examine the efficacy of the EM based approach in estimating
      the composition of experimental mixture sets from cell-by-cell measurements
      collected on a dynamic cell imaging platform. Towards this end, we apply the
      algorithm on hourly data collected for two different mixture compositions of
      A2058, HCT116 and SW480 cell lines for three scenarios: untreated, Lapatinib
      treated and Temsirolimus-treated. Additionally, we show how this methodology can
      provide a basis for comparing the killing rate of different drugs for a
      heterogeneous cancer tissue. This obviously has important implications for
      designing efficient drugs for treating heterogeneous malignant tumors.

PMID- 30222583
TI  - Cophenetic Median Trees.
AB  - Median tree inference under path-difference metrics has shown great promise for
      large-scale phylogeny estimation. Similar to these metrics is the family of
      cophenetic metrics that originates from a classic dendrogram comparison method
      introduced more than 50 years ago. Despite the appeal of this family of metrics,
      the problem of computing median trees under cophenetic metrics has not been
      analyzed. Like other standard median tree problems relevant in practice, as we
      show here, this problem is also NP-hard. NP-hard median tree problems have been
      successfully addressed by local search heuristics that are solving thousands of
      instances of a corresponding (local neighborhood) search problem. For the local
      neighborhood search problem under a cophenetic metric, the best known (naive)
      algorithm has a time complexity that is typically prohibitive for effective
      heuristic searches. Building on the pioneering work on path-difference median
      trees we develop efficient algorithms for Manhattan and Euclidean cophenetic
      search problems that improve on the naive solution by a linear and a quadratic
      factor, respectively. We demonstrate the performance and effectiveness of the
      resulting heuristic methods in a comparative study using benchmark empirical
      datasets.

PMID- 30222584
TI  - Detection of Colorectal Carcinoma Based on Microbiota Analysis using Generalized
      Regression Neural Networks and Nonlinear Feature Selection.
AB  - To obtain a screening tool for colorectal cancer (CRC) based on gut microbiota,
      we seek here to identify an optimal classifier for CRC detection as well as a
      novel nonlinear feature selection method for determining the most discriminative
      microbial species. In this study, the intestinal microflora in feces of 141
      patients were modeled using general regression neural networks (GRNNs) combined
      with the proposed feature selection method. The proposed model led to slightly
      higher accuracy (AUC=0.911) than previous studies (AUC<0.87). The results show
      that the Clostridium scindens and Bifidobacterium angulatum are indicators of
      healthy gut flora and CRC happens to reduce these bacterial species. In addition,
      Fusobacterium gonidiaformans was found to be closely correlated with the CRC. The
      occurrence of colorectal adenoma was not sufficiently discriminatory based on
      fecal microbiota implicating that the change of colonic flora happens in the
      advanced phase of CRC development rather than initial adenoma. Integrating the
      proposed model with fecal occult blood test (FOBT), the CRC detection accuracy
      remained nearly unchanged (AUC=0.915). The performance of proposed method is
      validated using independent cohorts from America and Austria. Our results suggest
      that proposed feature selection method combined with GRNN is potentially an
      accurate method for CRC detection.

PMID- 30222585
TI  - Event-Based Line Fitting and Segment Detection Using a Neuromorphic Visual
      Sensor.
AB  - This paper introduces an event-based luminance-free algorithm for line and
      segment detection from the output of asynchronous event-based neuromorphic
      retinas. These recent biomimetic vision sensors are composed of autonomous
      pixels, each of them asynchronously generating visual events that encode relative
      changes in pixels' illumination at high temporal resolutions. This frame-free
      approach results in an increased energy efficiency and in real-time operation,
      making these sensors especially suitable for applications such as autonomous
      robotics. The proposed algorithm is based on an iterative event-based weighted
      least squares fitting, and it is consequently well suited to the high temporal
      resolution and asynchronous acquisition of neuromorphic cameras: parameters of a
      current line are updated for each event attributed (i.e., spatio-temporally
      close) to it, while implicitly forgetting the contribution of older events
      according to a speed-tuned exponentially decaying function. A detection occurs if
      a measure of activity, i.e., implicit measure of the number of contributing
      events and using the same decay function, exceeds a given threshold. The speed
      tuned decreasing function is based on a measure of the apparent motion, i.e., the
      optical flow computed around each event. This latter ensures that the algorithm
      behaves independently of the edges' dynamics. Line segments are then extracted
      from the lines, allowing for the tracking of the corresponding endpoints. We
      provide experiments showing the accuracy of our algorithm and study the influence
      of the apparent velocity and relative orientation of the observed edges. Finally,
      evaluations of its computational efficiency show that this algorithm can be
      envisioned for high-speed applications, such as vision-based robotic navigation.

PMID- 30222586
TI  - Neural Learning Control of Strict-Feedback Systems Using Disturbance Observer.
AB  - This paper studies the compound learning control of disturbed uncertain strict
      feedback systems. The design is using the dynamic surface control equipped with a
      novel learning scheme. This paper integrates the recently developed online
      recorded data-based neural learning with the nonlinear disturbance observer (DOB)
      to achieve good ''understanding'' of the system uncertainty including unknown
      dynamics and time-varying disturbance. With the proposed method to show how the
      neural networks and DOB are cooperating with each other, one indicator is
      constructed and included into the update law. The closed-loop system stability
      analysis is rigorously presented. Different kinds of disturbances are considered
      in a third-order system as simulation examples and the results confirm that the
      proposed method achieves higher tracking accuracy while the compound estimation
      is much more precise. The design is applied to the flexible hypersonic flight
      dynamics and a better tracking performance is obtained.

PMID- 30222587
TI  - Dualityfree Methods for Stochastic Composition Optimization.
AB  - In this paper, we consider the composition optimization with two expected-value
      functions in the form of (1/n)Sigmani = 1 Fi((1/m)Sigmamj = 1 Gj(x))+R(x), which
      formulates many important problems in statistical learning and machine learning
      such as solving Bellman equations in reinforcement learning and nonlinear
      embedding. Full gradient- or classical stochastic gradient descent-based
      optimization algorithms are unsuitable or computationally expensive to solve this
      problem due to the inner expectation (1/m)Sigmamj = 1 Gj(x). We propose a
      dualityfree-based stochastic composition method that combines the variance
      reduction methods to address the stochastic composition problem. We apply the
      stochastic variance reduction gradient- and stochastic average gradient algorithm
      based methods to estimate the inner function and the dualityfree method to
      estimate the outer function. We prove the linear convergence rate not only for
      the convex composition problem but also for the case that the individual outer
      functions are nonconvex, while the objective function is strongly convex. We also
      provide the results of experiments that show the effectiveness of our proposed
      methods.

PMID- 30222588
TI  - Classifier Personalization for Activity Recognition using Wrist Accelerometers.
AB  - Inter-subject variability in accelerometer-based activity recognition may
      significantly affect classification accuracy, limiting a reliable extension of
      methods to new users. In this work we propose an approach for personalizing
      classification rules to a single person. We demonstrate that the method improves
      activity detection from wrist-worn accelerometer data on a four-class recognition
      problem of interest to the exercise science community, where classes are
      ambulation, cycling, sedentary, and other. We extend a previously published
      activity classification method based on support vector machines so that it
      estimates classification uncertainty. Uncertainty is used to drive data label
      requests from the user, and the resulting label information is used to update the
      classifier. Two different datasets - one from 33 adults with 26 activity types,
      and another from 20 youth with 23 activity types - were used to evaluate the
      method using leave-one-subject-out and leave-one-group-out cross validation. The
      new method improved overall recognition accuracy up to 11% on average, with some
      large person-specific improvements (ranging from -2% to +36%). The proposed
      method is suitable for online implementation supporting real-time recognition
      systems.

PMID- 30222589
TI  - Impulsive Consensus of Multiagent Systems With Limited Bandwidth Based on
      Encoding-Decoding.
AB  - Energy constrains are always significant to be considered in control of
      multiagent systems. Besides, nonlinear phenomena are often involved into such
      systems. In this paper, we discuss the impulsive consensus problem of nonlinear
      multiagent systems via impulsive protocol with limited bandwidth communication
      based on encoding-decoding. The scheme based on encoding-decoding with impulsive
      protocol is introduced to multiagent systems in general directed networks
      topology of which the graph is strongly connected. The impulsive protocols and
      limited bandwidth communication enhance the performance on energy saving and the
      involvement of nonlinear dynamics could suit more real-world cases. The design of
      encoders and decoders is presented, which is the key to achieve the goal that the
      information exchanged is subject to limited bandwidth communication. The
      conditions to guarantee the impulsive consensus and the conditions to avoid
      quantizer saturation are obtained. Moreover, the convergence rate of such
      multiagent systems are also characterized by the analysis of the exponential
      consensus. The numerical simulations are presented to support the theoretical
      results.

PMID- 30222590
TI  - Pornographic Image Recognition via Weighted Multiple Instance Learning.
AB  - In the era of Internet, recognizing pornographic images is of great significance
      for protecting children's physical and mental health. However, this task is very
      challenging as the key pornographic contents (e.g., breast and private part) in
      an image often lie in local regions of small size. In this paper, we model each
      image as a bag of regions, and follow a multiple instance learning (MIL) approach
      to train a generic region-based recognition model. Specifically, we take into
      account the regions' degree of pornography, and make three main contributions.
      First, we show that based on very few annotations of the key pornographic
      contents in a training image, we can generate a bag of properly sized regions,
      among which the potential positive regions usually contain useful contexts that
      can aid recognition. Second, we present a simple quantitative measure of a
      region's degree of pornography, which can be used to weigh the importance of
      different regions in a positive image. Third, we formulate the recognition task
      as a weighted MIL problem under the convolutional neural network framework, with
      a bag probability function introduced to combine the importance of different
      regions. Experiments on our newly collected large scale dataset demonstrate the
      effectiveness of the proposed method, achieving an accuracy with 97.52% true
      positive rate at 1% false positive rate, tested on 100K pornographic images and
      100K normal images.

PMID- 30222591
TI  - The etiological effect of a new low-frequency ESR1 variant on Mild Cognitive
      Impairment and Alzheimer's Disease: a population-based study.
AB  - Latent genetic variations of cholesterol metabolism-related genes in late-onset
      Alzheimer's disease, especially, as well as in mild cognitive impairment
      pathogenesis are still to be studied extensively. Thus, we performed the targeted
      sequencing of 12 nuclear receptor genes plus APOE which were involved in
      cholesterol content modulation to screen susceptible genetic variants and focused
      on a new risk variant ESR1 rs9340803 at 6q25.1 for both late-onset Alzheimer's
      disease (OR=3.30[1.84~4.22], p<0.001) and mild cognitive impairment
      (OR=3.08[1.75~3.89], p<0.001). This low-frequency variant was validated in three
      independent cohorts totaling 854 late-onset Alzheimer's disease cases, 1059 mild
      cognitive impairment cases and 1254 controls from nine provinces of China
      mainland. Preliminary functional study on it revealed decreased ESR1 expression
      in vitro. Besides, we detected higher serum Abeta1-40 concentration in
      participants carrying this variant (p=0.038) and lower plasma total cholesterol
      level in this variant carriers with late-onset Alzheimer's disease (p=0.009). In
      summary, we identified a susceptible variant which might contribute to developing
      mild cognitive impairment at earlier stage and Alzheimer's Disease later. Our
      study would provide new insight into the disease causation of late-onset
      Alzheimer's disease and could be exploited therapeutically.

PMID- 30222592
TI  - Antioxidant modifications induced by the new metformin derivative HL156A regulate
      metabolic reprogramming in SAMP1/kl (-/-) mice.
AB  - Aging is characterized by a reduced ability to defend against stress, an
      inability to maintain homeostasis, and an increased risk of disease. In this
      study, a metabolomics approach was used to identify novel metabolic pathways that
      are perturbed in a mouse model of accelerated aging (SAMP1/kl-/-) and to gain new
      insights into the metabolic associations of the metformin derivative HL156A.
      Extensive inflammation and calcification were observed in the tissues of the
      SAMP1/kl-/- mice with premature aging. In mouse embryonic fibroblasts (MEFs)
      obtained from SAMP1/kl-/- mice, we observed that HL156A induced FOXO1 expression
      through inhibition of the IGF-1/AKT/mTOR signaling pathways. Treatment of HL156A
      decreased reactive oxygen species production and enhanced mitochondrial
      transmembrane potential in SAMP1/kl-/- MEFs. A metabolomic profile analysis
      showed that HL156A increased the GSH/GSSG ratio in the kidneys of SAMP1/kl-/-
      mice (8-12 weeks old). In addition, treating SAMP1/kl-/- mice with HL156A (30
      mg/kg) for 4 weeks improved survival and decreased the significant elevation of
      oxidized GSH (GSSG) that was observed in SAMP1/kl-/- mice. In histological
      sections, HL156A administered SAMP1/kl-/- mice exhibited a decrease in excessive
      calcification. Based on these findings, we conclude that the new metformin
      derivative HL156A may inhibit oxidative damage by inducing glutathione metabolism
      and antioxidant pathways.

PMID- 30222593
TI  - Mechanisms of the anti-aging and prolongevity effects of caloric restriction:
      evidence from studies of genetically modified animals.
AB  - It is widely accepted that caloric restriction (CR) extends lifespan and
      suppresses various pathophysiological changes. CR suppresses growth
      hormone/insulin-like growth factor signaling and mechanistic target of rapamycin
      complex 1 activity, activates sirtuin and enhances mitochondrial redox
      regulation, but the exact mechanisms are still under debate. In this review, we
      discuss the mechanisms of CR using evidence from studies of animals that were
      genetically modified according to recent advances in molecular and genetic
      technologies, from the viewpoint of the adaptive response hypothesis proposed by
      Holliday (1989). We then explain the beneficial actions of CR, classified
      according to whether they operate under feeding or fasting conditions.

PMID- 30222594
TI  - Multiscale network dynamics between heart rate and locomotor activity are altered
      in schizophrenia.
AB  - OBJECTIVE: Changes in heart rate (HR) and locomotor activity reflect changes in
      autonomic physiology, behavior, and mood. These systems may involve interrelated
      neural circuits that are altered in psychiatric illness, yet their interactions
      are poorly understood. We hypothesized interactions between HR and locomotor
      activity could be used to discriminate patients with schizophrenia from controls,
      and would be less able to discriminate non-psychiatric patients from controls.
      APPROACH: HR and locomotor activity were recorded via wearable patches in 16
      patients with schizophrenia and 19 healthy controls. Measures of signal
      complexity and interactions were calculated over multiple time scales, including
      sample entropy, mutual information, and transfer entropy. A support vector
      machine was trained on these features to discriminate patients from controls.
      Additionally, time series were converted into a network with nodes comprised of
      HR and locomotor activity states, and edges representing state transitions. Graph
      properties were used as features. Leave-one-out cross validation was performed.
      To compare against non-psychiatric illness, the same approach was repeated in 41
      patients with atrial fibrillation (AFib) and 53 controls. MAIN RESULTS: Network
      features enabled perfect discrimination of schizophrenia patients from controls
      with an areas under the receiver operating characteristic curve (AUC) of 1.00 for
      training and test data. Other bivariate measures of interaction achieved lower
      AUCs (train 0.98, test 0.96), and univariate measures of complexity achieved the
      lowest performance. Conversely, interaction features did not improve
      discrimination of AFib patients from controls beyond univariate approaches.
      SIGNIFICANCE: Interactions between HR and locomotor activity enabled perfect
      discrimination of subjects with schizophrenia from controls, but these features
      were less performant in a non-psychiatric illness. This is the first quantitative
      evaluation of interactions between physiology and behavior in patients with
      psychiatric illness.

PMID- 30222595
TI  - Dual versus triple antithrombotic therapy after percutaneous coronary
      intervention or acute coronary syndrome in patients with indication for
      anticoagulation: an updated meta-analysis.
AB  - BACKGROUND: For patients who have an indication for anticoagulation, it is
      controversial whether dual therapy with an oral anticoagulant and single
      antiplatelet agent can be used after percutaneous coronary intervention (PCI) or
      acute coronary syndrome (ACS) instead of triple therapy with an oral
      anticoagulant and dual antiplatelet therapy. PARTICIPANTS AND METHODS: Twelve
      observational studies and four clinical trials were identified from three
      electronic databases from their inception to December, 2017. Pooled estimates
      were calculated using a random-effects model for meta-analysis. RESULTS: Compared
      with the triple therapy, dual therapy was associated with significantly lower
      risk of major bleeding [relative risk (RR), 0.63; 95% confidence interval (CI),
      0.50-0.80] without statistically significant increase in major adverse cardiac
      events (RR, 1.04; 95% CI, 0.84-1.29), all-cause death (RR, 1.15; 95% CI, 0.77
      1.71), cardiac death (RR, 1.04; 95% CI, 0.67-1.61), myocardial infarction (RR,
      1.25; 95% CI, 0.98-1.59), stroke (RR, 1.27; 95% CI, 0.79-2.06), stent thrombosis
      (RR, 1.52; 95% CI, 0.96-2.41), and repeat revascularization (RR, 1.15; 95% CI,
      0.87-1.52). Although risks of myocardial infarction and stent thrombosis were
      marginally higher in the dual therapy group, this trend was attenuated after
      excluding studies that exclusively included patients undergoing PCI for ACS, but
      not stable coronary artery disease. CONCLUSION: Dual therapy may be a reasonable
      alternative to triple therapy after PCI in patients with indication for chronic
      anticoagulation. However, further studies are needed to investigate efficacy of
      dual therapy, especially in the patients with higher ischemic risk, such as in
      ACS.

PMID- 30222596
TI  - Screening for Postpartum Depression by Hospital-Based Perinatal Nurses.
AB  - PURPOSE: The primary purpose of this study was to evaluate acceptability by new
      mothers of postpartum depression (PPD) screening and education about community
      resources by hospital-based perinatal nurses. A secondary purpose was to
      determine further screening for PPD that women received by community providers in
      the first few weeks after birth. METHODS: The study design was descriptive. As
      per standard practice on the unit, all new mothers were screened for depression
      the night before hospital discharge using the Edinburgh Postnatal Depression
      Scale (EPDS). New mothers identified as high risk for depression by EPDS scores
      greater than or equal to 10 (n = 75) and a comparison group of mothers at low
      risk for depression with EPDS scores less than 10 (n = 26) were recruited from an
      academic health sciences center. Participants were contacted by telephone 2 to 4
      weeks later and asked about the acceptability of screening for depression and
      education about community resources by hospital-based perinatal nurses, as well
      as if they had received further screening for depression by community providers.
      Descriptive and correlational statistics were used to analyze data. RESULTS: The
      majority of new mothers found it acceptable to be screened for depression and
      educated about community resources by hospital-based perinatal nurses. Many new
      mothers were not asked about depressive symptoms by community providers. There
      was no significant correlation between demographics and depression risk. CLINICAL
      IMPLICATIONS: New mothers viewed depression screening and receiving information
      on community resources as a positive part of their care. Communication between
      inpatient and community caregivers should be improved so that new mothers can
      benefit from seamless depression assessment, evaluation, and treatment.

PMID- 30222597
TI  - Olfaction in female Wistar rats is influenced by dopaminergic periglomerular
      neurons after nigral and bulbar lesions.
AB  - Hyposmia is found in Parkinsonian patients decades before the onset of motor
      disorders. The same occurs with sleep disorders, especially infuencing rapid eye
      movement (REM) sleep, which affect a large percentage of people who have
      Parkinson's disease. These two disturbances presumably are closely related to a
      dopaminergic dysfunction. Therefore, we propose that selective lesions, induced
      by rotenone, of the periglomerular neurons within the olfactory bulb or of the
      nigrostriatal pathway could result in hyposmia. In addition, we hypothesized that
      REM sleep deprivation (REMSD) could have potential to generate a synergistic
      olfactory impairment in both lesion paradigms. The results indicated that
      rotenone-induced nigrostriatal lesions in female Wistar rats were associated with
      odor preference changes, similar to hedonic tone impairment, but without a
      supposed potentiation triggered by REMSD. The nigrostriatal injury negatively
      affected olfaction performance, which was counteracted, functionally, by REMSD.
      However, injury to periglomerular neurons was less influenced by REMSD, as
      olfactory performance was restored after rebound sleep. We conclude that female
      rats present a pattern of olfactory discrimination/preference that is dependent
      on the activities of the nigrostriatal and the main olfactory pathways.

PMID- 30222598
TI  - US FDA Breast Implant Postapproval Studies: Long-term Outcomes in 99,993
      Patients.
AB  - OBJECTIVE: To analyze the long-term safety and efficacy outcomes of patients with
      breast implants. SUMMARY BACKGROUND DATA: Research is ongoing regarding the
      safety of silicone breast implants. Despite the number of patients with breast
      implants followed by United States Food and Drug Administration large
      postapproval studies (LPAS), this database has not been thoroughly analyzed or
      reported. METHODS: This is a multicentered, cohort study. LPAS prospectively
      monitor long-term implant-related outcomes and systemic harms for silicone/saline
      implants from 2 manufacturers (Allergan and Mentor) placed for primary/revision
      augmentation/reconstruction. Systemic harms, self-harm, and reproductive outcomes
      are compared with normative data. Implant-related complications are analyzed by
      implant composition and operative indication in the short and long terms.
      RESULTS: LPAS data includes 99,993 patients, 56% of implants were silicone for
      primary augmentation. Long-term magnetic resonance imaging surveillance is under
      5%. Compared with normative data, silicone implants are associated with higher
      rates of Sjogren syndrome (Standardized incidence ratio [SIR]8.14), scleroderma
      (SIR 7.00), rheumatoid arthritis (SIR5.96), stillbirth (SIR4.50), and melanoma
      (SIR3.71). One case of BI-ALCL is reported. There is no association with suicide.
      In the short term, rupture is higher for saline (2.5% vs. 0.5%, P < 0.001), and
      capsular contracture higher for silicone (5.0% vs. 2.8%, P < 0.001). At 7 years,
      reoperation rate is 11.7% for primary augmentation, and 25% for primary/revision
      reconstruction. Capsular contracture (III/IV) occurs in 7.2% of primary
      augmentations, 12.7% primary reconstructions, and is the most common reason for
      reoperation among augmentations. CONCLUSIONS: This is the largest study of breast
      implant outcomes. Silicone implants are associated with an increased risk of
      certain rare harms; associations need to be further analyzed with patient-level
      data to provide conclusive evidence. Long-term safety and implant-related
      outcomes should inform patient and surgeon decision-making when selecting
      implants.

PMID- 30222599
TI  - Type B Aortic Dissection Diagnosed by Left-Sided Transthoracic Ultrasonography in
      a Woman With Preeclampsia.

PMID- 30222600
TI  - Measuring Clinical Productivity of Anesthesiology Groups: Surgical Anesthesia at
      the Facility Level.
AB  - Benchmarking and comparing group productivity is an essential activity of data
      driven management. For clinical anesthesiology, accomplishing this task is a
      daunting effort if meaningful conclusions are to be made. For anesthesiology
      groups, productivity must be done at the facility level in order to reduce some
      of the confounding factors. When industry or external comparisons are done, then
      the use of total ASA units per anesthetizing sites allows for overall
      productivity comparisons. Additional productivity components (total ASA units/h,
      h/case, h/operating room/d) allow for leaders to develop productivity dashboards.
      With the emergence of large groups that provide care in multiple facilities,
      these large groups can choose to invest more effort in collecting data and
      comparing facility productivity internally with group-defined measurements
      including total ASA units per full time equivalent.

PMID- 30222601
TI  - Succinylcholine and Intracranial Pressure.
AB  - Intracranial and Hemodynamic Changes after Succinylcholine Administration in
      Cats. By Cottrell JE, Hartung J, Giffin JP, and Shwiry B. Anesthesia & Analgesia
      1983; 62:1006-9. Reprinted with permission.Bolus injections of succinylcholine
      (1.5 mg/kg) significantly increased intracranial pressure (ICP) in cats under
      normal conditions from control levels of 8 +/- 1 mmHg to 16 +/- 3 mmHg (+/- SEM,
      P less than 0.01), and in the presence of artificially increased ICP from control
      levels of 27 +/- 1 mmHg to 47 +/- 4 mmHg (P less than 0.01). These approximately
      100% increases in ICP were accompanied by a transitory decrease in mean arterial
      pressure (approximately 10 s), followed by a 15 to 20% increase (P less than
      0.05). Pulmonary arterial pressure increased 20 to 30% (P less than 0.05). These
      results, when considered in conjunction with results previously obtained in
      humans, suggest that succinylcholine may be contraindicated in neurosurgical
      patients.

PMID- 30222602
TI  - Inadvertent Extracorporeal Membrane Oxygenation Cannulation across a Patent
      Foramen Ovale.

PMID- 30222603
TI  - Follicular Dendritic Cell Sarcoma With Indolent T-Lymphoblastic Proliferation Is
      Associated With Paraneoplastic Autoimmune Multiorgan Syndrome.
AB  - Nonclonal expansions of immature T cells outside of the thymus, termed indolent T
      lymphoblastic proliferation (iT-LBP), have been identified in rare
      lymphoproliferative disorders. We report that iT-LBP is a frequent finding in
      cases of follicular dendritic cell sarcoma (FDCS), and shows an association with
      paraneoplastic autoimmune multiorgan syndrome (PAMS). We studied 31 cases of FDCS
      by paraffin immunohistochemistry using antibodies to CD21, CD23, CD35, clusterin,
      CXCL13, podoplanin, CD3, CD4, CD8, CD20, CD1a, and TdT. Chart review was
      performed to characterize the clinical behavior including evidence of autoimmune
      disease. FDCS occurred in a wide variety of nodal and extranodal sites. Fourteen
      of 31 (45%) cases contained immature TdT-positive T cells; in 5 cases these cells
      were numerous and present throughout the tumor. Four of these 5 patients with
      numerous immature T cells developed autoimmune disease, clinically categorized as
      PAMS and/or myasthenia gravis. PAMS persisted after tumor resection, causing
      severe morbidity and mortality. These findings suggest that the neoplastic
      follicular dendritic cells can recruit or foster the proliferation of immature T
      cells and that these cells may play a role in mediating PAMS. Recognition of iT
      LBP in FDCS is important to avoid misdiagnosis as thymoma or T-lymphoblastic
      lymphoma, and may predict serious autoimmune complications in some patients.

PMID- 30222604
TI  - Pathologic Subtypes of Lung Adenocarcinoma Brain Metastasis Is a Strong Predictor
      of Survival After Resection.
AB  - Primary lung adenocarcinoma is classified according to predominant
      histopathologic architecture into lepidic, papillary, acinar, solid, and
      micropapillary subtypes. These subtypes are related to overall survival in
      primary lung adenocarcinoma. The main goal of our work was to evaluate the
      prognostic impact of this classification on surgical resection of brain
      adenocarcinoma metastases in 97 patients with surgically resected brain
      metastases of lung adenocarcinoma from 2008 to 2017. Histopathologic subtype is
      associated with overall survival (P=0.0085): 30.1+/-5.6 months for papillary
      predominant pattern, 26.5+/-6.3 months for acinar-predominant pattern, 13.8+/-1.4
      months for solid pattern, 11.6+/-10.1 for micropapillary pattern. A "low grade"
      group comprising acinar and papillary-predominant pattern tumors showed a longer
      overall survival (28.5+/-4.1 mo) when compared with high-grade-predominant
      pattern (solid and micropapillary patterns) (13.7+/-1.4 mo), P=0.0011. On
      multivariate analysis, age below 55 years at the time of resection (hazard ratio,
      3.56; 95% confidence interval, 1.12-11.31) and groups of architectural patterns
      (hazard ratio, 4.25; 95% confidence interval, 1.83-9.9) were related to overall
      survival (P=0.031 and 0.00078, respectively). Predominant architectural pattern
      evaluated on the surgical specimen of brain metastasis is a major prognostic
      factor of overall survival in metastatic lung adenocarcinoma.

PMID- 30222605
TI  - An investigation of pressure profiles and wearer comfort during walking with a
      transtibial hydrocast socket.
AB  - OBJECTIVE: to conduct an investigation of the transtibial hydrocast socket
      interface pressures during walking and explore potential relationships between
      pressures experienced and resultant wearer comfort. DESIGN: In this cross
      sectional study, pressure data at the limb and hydrocast socket interface during
      walking were collected from sixteen users of the hydrocast socket. The pressures
      at this interface were described by location, magnitude and duration for all
      participants and were compared between the most and least comfortable
      participants. RESULTS: High pressures were found about the bony prominences of
      the residual limb, especially the tibial crest of the anterior distal region.
      Factors identified as potentially causing discomfort (p<0.1, d>0.80) were high
      peak pressures at the anterior proximal region, and longer durations of
      submaximal loading at the lateral proximal region and the anterior and medial
      distal regions. High pressure variability at the anterior proximal region may
      also contribute to discomfort (p=0.106, d=0.88). CONCLUSIONS: The hydrocast
      socket interface pressures have been described for a cohort of users. A number of
      differences were found in the pressure profiles of the most and least comfortable
      participants. These differences suggest trends between the identified pressure
      parameters and resultant wearer comfort. Future studies should confirm these
      exploratory results.

PMID- 30222607
TI  - The p.R47H Variant of TREM2 Gene is Associated With Late-onset Alzheimer Disease
      in Colombian Population.
AB  - OBJECTIVE: We evaluated the association of several single-nucleotide
      polymorphisms in the triggering receptor expressed on myeloid cells 2 (TREM2)
      gene in a Colombian sample of late-onset Alzheimer disease (LOAD). METHODS: The
      p.Q33* (rs104894002), p.R47H (rs75932628), p.R62H (rs143332484), and p.D87N
      (rs142232675) variants of TREM2 gene were directly genotyped using KASPar
      technology in 358 cases and 329 healthy controls. Sanger sequencing was used to
      validate >10% of KASPar's results. The Fisher exact test was used to compare the
      distribution of allelic and genotype frequency between cases and controls, and
      the Bonferroni correction was set at P<0.05. RESULTS: The minor allele frequency
      of rs75932628-T was 0.009 in cases and was not found in any healthy controls
      which suggests a significant association between rs75932628-T and LOAD risk in
      our sample (P=0.010). The rs143332484-T variant did not exhibit a significant
      association (P=0.160), whereas rs104894002 and rs142232675 were not found.
      CONCLUSIONS: Our findings suggest that the rs75932628-T variant of TREM2 is an
      important risk factor for LOAD in the Colombian population.

PMID- 30222606
TI  - Rapidly Progressive Dementia in the Outpatient Clinic: More Than Prions.
AB  - BACKGROUND: Published approaches to the evaluation and management of patients
      with rapidly progressive dementia (RPD) have been largely informed by experience
      at academic hospitals and national centers specializing in the diagnosis of
      Creutzfeldt-Jakob disease. Whether these approaches can be applied to patients
      assessed within lower-acuity outpatient settings is unknown. METHODS: A total of
      96 patients with suspected RPD were assessed within the Washington University
      School of Medicine (Saint Louis, MO) outpatient memory clinic from February 2006
      to February 2016. Consensus etiologic diagnoses were established following
      independent review of clinical data by 2 dementia specialists. RESULTS: In total,
      67/90 (70%) patients manifested with faster-than-expected cognitive decline
      leading to dementia within 2 years of symptom onset. Female sex (42/67, 63%),
      median patient age (68.3 y; range, 45.4 to 89.6), and years of education (12 y;
      range, 6 to 14) were consistent with clinic demographics. Atypical presentations
      of common neurodegenerative dementing illnesses accounted for 90% (60/67) of RPD
      cases. Older age predicted a higher odds of amnestic Alzheimer disease dementia
      (OR, 2.1 per decade; 95% CI, 1.1-3.8; P=0.02). Parkinsonism (OR, 6.9; 95% CI, 1.6
      30.5; P=0.01) or cortical visual dysfunction (OR, 10.8; 95% CI, 1.7-69.4; P=0.01)
      predicted higher odds of another neurodegenerative cause of RPD, including
      sporadic Creutzfeldt-Jakob disease. CONCLUSIONS AND RELEVANCE: The clinical
      environment influences the prevalence of RPD causes. The clinical evaluation
      should be adapted to promote detection of common causes of RPD, specific to the
      practice setting.

PMID- 30222608
TI  - Coordinating the prevention, treatment, and care continuum for HIV-associated
      tuberculosis in prisons: a health systems strengthening approach.
AB  - PURPOSE OF REVIEW: To advance a re-conceptualized prevention, treatment, and care
      continuum (PTCC) for HIV-associated tuberculosis (TB) in prisons, and to make
      recommendations for strengthening prison health systems and reducing HIV
      associated TB morbidity and mortality throughout the cycle of pretrial detention,
      incarceration, and release. RECENT FINDINGS: Despite evidence of increased HIV
      associated TB burden in prisons compared to the general population, prisoners
      face entrenched barriers to accessing anti-TB therapy, antiretroviral therapy,
      and evidence-based HIV and TB prevention. New approaches, suitable for the
      complexities of healthcare delivery in prisons, have emerged that may address
      these barriers, and include: novel TB diagnostics, universal test and treat for
      HIV, medication-assisted treatment for opioid dependence, comprehensive
      transitional case management, and peer navigation, among others. SUMMARY:
      Realizing ambitious international HIV and TB targets in prisons will only be
      possible by first addressing the root causes of the TB/HIV syndemic, which are
      deeply intertwined with human rights violations and weaknesses in prison health
      systems, and, second, fundamentally re-organizing HIV and TB services around a
      coordinated PTCC. Taking these steps can help ensure universal access to
      comprehensive, good-quality, free and voluntary TB/HIV prevention, treatment, and
      care, and advance efforts to strengthen health resourcing, staffing, information
      management, and primary care access within prisons.

PMID- 30222609
TI  - Treatment of drug-susceptible tuberculosis among people living with human
      immunodeficiency virus infection: an update.
AB  - PURPOSE OF REVIEW: The present review describes recent advances in the treatment
      of drug-susceptible tuberculosis (DS-TB) among people living with human
      immunodeficiency virus (PLWH). RECENT FINDINGS: Higher than standard rifampicin
      doses (>10 mg/kg/day) are well tolerated and have improved sterilizing activity.
      Standard pyrazinamide doses may result in low drug exposures; modeling reveals
      that higher doses (>25 mg/kg/day) may be required to reach target levels,
      although safety is unknown. Four-month fluoroquinolone-containing regimens are
      not recommended in the 2017 World Health Organization DS-TB treatment guidelines.
      These guidelines also recommend fixed-dose combination (FDC) therapy over single
      drug formulations based on patient preference, though FDC is not associated with
      improved outcomes. Treatment for 6 months is recommended, with an emphasis on
      expanded antiretroviral therapy (ART) coverage and monitoring for relapse among
      those not started on ART within 8 weeks of tuberculosis treatment. Directly
      observed therapy (DOT) is recommended over self-administered therapy, as is daily
      therapy over intermittent therapy - both are associated with better tuberculosis
      outcomes. SUMMARY: Current WHO tuberculosis treatment guidelines recommend 6
      months of daily tuberculosis treatment for PLWH who have DS-TB, and timely ART
      initiation. Higher rifampin and pyrazinamide doses may enhance treatment
      effectiveness, but safety data are needed. DOT and FDC therapy are recommended.

PMID- 30222610
TI  - Conservative Management of Placenta Accreta Spectrum.
AB  - The purpose of this review was to assist obstetricians and gynecologists in
      considering the most appropriate conservative treatment option to manage women
      with placenta accreta spectrum according to their individual need and local
      expertise of the heath care team. The issue is challenging, as the quality of
      evidence with regard to efficacy is poor, and is mainly based on retrospective
      studies with limited sample size.

PMID- 30222611
TI  - Evaluation of the Neuropathic Component of Chronic Low Back Pain.
AB  - OBJECTIVES: Assessment of neuropathic pain in chronic low back syndromes is
      important. However, there is currently no gold standard for its diagnosis. The
      aim of this observational cross-sectional study was to assess the neuropathic
      component of pain in various chronic low back pain syndromes using a range of
      diagnostic tests. MATERIALS AND METHODS: Included in this study were 63 patients
      with chronic axial low back pain (ALBP), 48 patients with chronic radicular
      syndromes (CRS) comprising 23 with discogenic compression (CDRS) and 25 with
      lumbar spinal stenosis (LSS), and 74 controls. PainDETECT questionnaire (PDQ),
      quantitative sensory testing (QST), and skin biopsy with evaluation of
      intraepidermal nerve fiber density (IENFD) were used to assess the neuropathic
      pain component. RESULTS: Positive PDQ (>=19) was obtained more frequently in
      patients with CDRS and LSS (26.1% and 12.0%, respectively) compared with patients
      with ALBP (1.6%, P<0.001). The proportion of patients with sensory loss confirmed
      by QST was lowest in the ALBP subgroup (23.8%) compared with CDRS (47.8%), and
      LSS (68.0%) subgroups (P<0.001). A reduction in IENFD was disclosed in a
      proportion of up to 52.0% of affected roots in patients with CRS. DISCUSSION:
      Neuropathic pain is quite frequent in CRS, and QST reveals sensory loss as a
      frequent abnormality in patients with CRS. Using a cut-off value of 19, PDQ
      identified a neuropathic component in a relatively low proportion of patients
      with CRS. CRS may be associated with a reduction in IENFD.

PMID- 30222613
TI  - The Effects of Motor Imagery on Pain and Range of Motion in Musculoskeletal
      Disorders: A Systematic Review Using Meta-Analysis.
AB  - INTRODUCTION: In recent years, there has been an increase in the use of motor
      imagery (MI) in the rehabilitation of musculoskeletal pain conditions. Across the
      literature, most reviews have yet to consider Laterality Judgement Task training
      as a form of MI method. This review aimed to evaluate the effectiveness of using
      MI as an adjunct to standard rehabilitation on the improvement of pain and range
      of motion parameters when managing patients with musculoskeletal pain conditions.
      METHODS: Searches of 8 major electronic databases were conducted. Data for pain
      and range of motion were extracted. Meta-analyses (where possible) with either a
      fixed or random-effect(s) model, standardized mean differences (SMDs), and tests
      of heterogeneity were performed. RESULTS: Eight clinical controlled trials were
      identified and included in the meta-analyses. When compared with standard
      rehabilitation alone, the adjunctive role of MI provided superior pain relief
      (pooled SMD, -2.25; 95% confidence interval, -4.11 to -0.4; P=0.02), and greater
      improvement in range of motion (pooled SMD, 3.04; 95% confidence interval, 0.66
      5.43; P=0.01) in chronic musculoskeletal pain disorders. DISCUSSION: The results
      suggest that MI may be effective for pain relief and improvement in range of
      motion among chronic musculoskeletal pain conditions, although conclusion is
      based on a limited certainty of evidence as assessed using the GRADES (Grading of
      Recommendation, Assessment, Development and Evaluation) approach.

PMID- 30222612
TI  - Clinician Response to Aberrant Urine Drug Test Results of Patients Prescribed
      Opioid Therapy for Chronic Pain.
AB  - OBJECTIVE: Urine drug testing (UDT) is recommended for patients who are
      prescribed opioid medications, but little is known about the various strategies
      clinicians use to respond to aberrant UDT results. We sought to examine changes
      in opioid prescribing and implementation of other risk reduction activities
      following an aberrant UDT. METHODS: In a national cohort of Veterans Affairs
      patients with new initiations of opioid therapy through 2013, we identified a
      random sample of 100 patients who had aberrant positive UDTs (results positive
      for nonprescribed/illicit substance), 100 who had aberrant negative UDTs (results
      negative for prescribed opioid), and 100 who had expected UDT results. We
      examined medical record data for opioid prescribing changes and risk reduction
      strategies in the 12 months following UDT. RESULTS: Following an aberrant UDT,
      17.5% of clinicians documented planning to discontinue or change the opioid dose
      and 52.5% initiated another strategy to reduce opioid-related risk. In
      multivariate analyses, variables associated with a planned change in opioid
      prescription status were having an aberrant positive UDT (odds ratio [OR], 30.77;
      95% confidence interval [CI], 5.92-160.10) and higher prescription opioid dose
      (OR, 1.01; 95% CI, 1.01-1.02). The only variable associated with implementation
      of other risk reduction activities was having an aberrant positive UDT (OR, 0.29;
      95% CI, 0.16-0.55). DISCUSSION: The majority of clinicians enacted some type of
      opioid prescribing or other change to reduce risk following an aberrant UDT, and
      the action depended on whether the result was an aberrant positive or aberrant
      negative UDT. Experimental studies are needed to develop and test strategies for
      managing aberrant UDT results.

PMID- 30222614
TI  - Staircase-evoked Pain May be More Sensitive Than Traditional Pain Assessments in
      Discriminating Analgesic Effects: A Randomized, Placebo-controlled Trial of
      Naproxen in Patients With Osteoarthritis of the Knee.
AB  - OBJECTIVES: Analgesic trials often fail to show a significant effect even when
      medications with known efficacy are tested. This could be attributed to
      insufficient assay sensitivity of analgesic trials, which may be due, in part, to
      the insensitivity of pain-related outcome measures. The aim of this
      methodological study was to assess the responsiveness of evoked pain generated by
      the staircase procedure compared with other commonly used pain outcomes in knee
      osteoarthritis. METHODS: This was a randomized, double-blind, placebo-controlled,
      cross-over trial of 1-week treatment of naproxen versus placebo. Participants
      were assigned to one of the 2 treatment sequences (naproxen-placebo or placebo
      naproxen). Pain-at-rest, evoked pain using the Staircase-Evoked Pain Procedure
      (StEPP), pain diary, and Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC) data were collected before and at the end of each treatment
      sequence. RESULTS: A total of 55 osteoarthritis patients (30 M, 25 F) completed
      the study. Among all pain assessments, evoked pain was the most sensitive outcome
      to detect treatment effects, with Standardized Effect Size (SES) of 0.47 followed
      by the WOMAC and pain-at-rest with SES of 0.43 and 0.36, respectively. Sample
      size calculations demonstrated that compared with spontaneous pain, the evoked
      pain model reduces required number of subjects by 40%. DISCUSSION: Study results
      support our hypothesis that evoked pain using the StEPP may demonstrate greater
      responsiveness to treatment effects compared with traditional pain-related
      outcome measures. Accordingly, these results may facilitate development and
      validation of other chronic pain-related evoked pain models, which could
      contribute to future research and development of new analgesics.

PMID- 30222615
TI  - Clinical Outcomes and Central Pain Mechanisms are Improved After Upper Trapezius
      Eccentric Training in Female Computer Users With Chronic Neck/Shoulder Pain.
AB  - OBJECTIVES: The effects of eccentric exercises on clinical outcomes and central
      pain mechanisms are unclear in neck/shoulder pain (NSP). The aims were to: (1)
      evaluate the clinical impact of unilateral eccentric training in female computer
      users with chronic NSP; (2) compare pressure pain sensitivity, temporal summation
      of pain (TSP); and conditioned pain modulation (CPM) in female office workers
      with and without NSP; and (3) assess sensitization and central pain responses
      after training. METHODS: In part A, 20 females with NSP were compared with 20
      controls. In part B, the NSP group underwent a 5-week upper trapezius eccentric
      training program. Participants reported their pain intensity and completed the
      Neck Disability Index, and the Disabilities of the Arm, Shoulder and Hand
      questionnaire. Pressure pain thresholds (PPTs) were assessed over the neck and
      forearm. Cuff algometry identified pain detection threshold (PDT) and pain
      tolerance thresholds (PTT). TSP was evaluated by visual analog scale pain scores
      during 10 repetitive cuff stimulations. CPM was calculated as the difference in
      PDT with and without a conditioning painful stimulus. Outcomes were measured at
      baseline and after intervention. Pain intensities were collected at 3- and 6
      month follow-up. RESULTS: Pain and disability decreased after intervention
      (P<0.05) and at follow-ups (P=0.002). The NSP group showed reduced PTT (P<=0.02),
      but no differences in TSP (P=0.947) or CPM (P=0.059) compared with controls.
      After training, participants with NSP had improved CPM, PPTs, and PTT at the
      nontreated side (P<0.05). DISCUSSION: Eccentric training improved pain and
      disability, reduced sensitization, and enhanced CPM efficiency in female computer
      users with NSP.

PMID- 30222616
TI  - Modification of Descending Analgesia in Aging: Critical Role of the Prefrontal
      Cortex.
AB  - OBJECTIVE: Aging has been associated with increases in pain threshold and
      reductions in tolerance threshold, as well as a deficiency in endogenous pain
      inhibition. Top-down pain modulation mainly involves the frontal cortex network,
      which is also one of the most vulnerable brain regions in aging. As the frontal
      cortex also sustains executive functions, we aimed to determine whether
      reductions in executive functions subtended by the frontal network are associated
      with the lack of descending inhibitor control in pain-free elderly participants.
      METHODS: Executive functions were assessed in pain-free elderly participants
      using neuropsychological tests. Endogenous inhibition of pain was investigated
      using the paradigm of conditioned pain modulation. We compared pain thresholds
      before and after the conditioned pain modulation procedure in older and younger
      participants and in seniors with poor and good performances on executive tests.
      RESULTS: Younger participants showed a significant inhibitory effect of phasic
      pain during prolonged pain stimulation. Older participants with good performance
      on executive tests showed an absence of inhibiting effect, whereas older
      participants with poor performance showed a facilitating effect, indicating a
      significant link between cognitive functions and mechanisms of endogenous
      inhibition of pain. DISCUSSION: These results highlight a significant link
      between cognitive functions and mechanisms of endogenous inhibition of pain and
      open new perspectives in investigations of chronic pain in aging.

PMID- 30222617
TI  - Noninvasive neuromodulation techniques for the management of phantom limb pain: a
      systematic review of randomized controlled trials.
AB  - Neuromodulation techniques work by modulating pain perception by inducing changes
      in polarity of the neuronal membrane and thereby cortical excitability. The aim
      of this review is to evaluate the efficiency and safety of noninvasive
      neuromodulation techniques for phantom limb pain (PLP). A systematic literature
      search in the PubMed, Scopus, Web of Science, and Cochrane Library databases was
      performed to identify studies investigating the effects of noninvasive
      neuromodulation for PLP. The included journal articles were assessed with Furlan
      et al.'s method for examining the risk of bias to assess methodologic quality,
      and evidence was graded using the GRADE approach. The literature search
      identified 239 studies. Of these 239, four studies fulfilled the inclusion
      criteria and were included for data extraction. Two of the studies focused on
      repetitive transcranial magnetic stimulation (rTMS) whereas two other
      concentrated on transcranial direct current stimulation (tDCS). The present
      review showed that there is conflicting evidence to support the use of tDCS in
      short term and moderate evidence to support the use of rTMS in immediate and
      short term. It is important to recognize that this evidence comes from a very
      small sample size. No serious adverse effects were reported. Further information
      from randomized controlled trials with larger sample size investigating immediate
      and short-term and long-term effects are needed to clarify the best effective
      stimulation parameters and number of sessions of tDCS and rTMS for PLP.

PMID- 30222618
TI  - Microendoscopic Decompression for Lumbar Spinal Stenosis With Degenerative
      Spondylolisthesis: The Influence of Spondylolisthesis Stage (Disc Height and
      Static and Dynamic Translation) on Clinical Outcomes.
AB  - STUDY DESIGN: This study was a retrospective subgroup analysis of prospective
      cohort data. OBJECTIVE: The main objectives of this study were to develop a
      classification of degenerative spondylolisthesis (DS) and concurrent lumbar
      spinal stenosis (LSS) based on pathologic stage, and to determine how these
      subtypes of DS affect outcomes for minimally invasive (MIS) decompression SUMMARY
      OF BACKGROUND DATA:: DS with LSS is a common clinical scenario, yet there is no
      consensus on optimal treatment. Natural history of DS is described as early
      degenerative damage, followed by instability, and eventual restabilization via
      spondylotic changes. MIS decompression surgery has become increasingly popular,
      but the effect of DS subtypes on clinical outcomes after MIS decompression is
      unknown. PATIENTS AND METHODS: From 2008 to 2013, all patients who underwent
      microendoscopic laminotomy for single-level LSS with DS were included. In total,
      218 patients (91 male, 127 female individuals) were reviewed. DS pathologic
      staging was defined as early, advanced, or end stage, based on percent slippage
      (10% slippage), degree of dynamic instability (3 mm), and disc height. The
      following variables were evaluated preoperatively and >2 years postoperatively
      and compared among groups: Japanese Orthopaedic Association (JOA) score, JOA
      recovery rate, and Visual Analog Scale low back pain. RESULTS: In total, 173
      patients were included in final analysis. Final follow-up period was 2.3 years.
      Average JOA recovery rate was 63.8%. There were no significant differences in JOA
      recovery and Visual Analog Scale among 3 DS stages (P>0.05). In total, 9.8% of
      patients required additional spine surgery, with 5% requiring subsequent fusion.
      All patients who required subsequent fusion were in the advanced stage DS group.
      CONCLUSIONS: Microendoscopic decompression is an effective treatment for patients
      with DS and concurrent LSS, with only 5% of patients requiring subsequent fusion
      at over 2-year follow-up, and another 5% requiring revision or adjacent segment
      decompression. The advanced stage DS group, indicating a >10% anterolisthesis
      and/or >3 mm of dynamic instability, was more likely to require additional
      surgery.

PMID- 30222619
TI  - Guidelines on How to Perform a Meta-Analysis in Spine Surgery: Strengths and
      Weaknesses of Design.
AB  - There are many questions in the literature that remain unanswered due to the
      paucity of available subjects or the large sample size needed to detect a
      difference. A meta-analysis consists of integrating together data from multiple
      studies into one larger data set in order to increase the subject size and power
      of a paper. In essence, it is a systematic review in which one uses statistical
      methods to summarize the results of these studies. It is important that a meta
      analysis be performed in a systematic and orderly manner with the assistance of a
      statistician. When carried out correctly, these studies serve as powerful tools
      to help us better address our knowledge. Because of their complexity, they are
      prone to bias at multiple levels. This article will discuss the steps involved in
      performing a meta-analysis, select good studies, as well as explain the
      statistics conducted in these studies. Furthermore, we will discuss examples from
      the literature that demonstrate a good meta-analysis.

PMID- 30222620
TI  - Impact of Epidural Versus General Anesthesia on Major Lumbar Surgery in Elderly
      Patients.
AB  - STUDY DESIGN: This was a retrospective comparative study. OBJECTIVE: The main
      objective of this study was to investigate the effects of epidural anesthesia
      (EA) versus general anesthesia (GA) in elderly patients undergoing lower lumbar
      spine fusion surgeries. SUMMARY OF BACKGROUND DATA: Lumbar spine surgery can be
      performed under GA or regional anesthesia. GA is more commonly used in lumbar
      spine surgery, which renders the patient motionless throughout the procedure and
      provides a secure airway. Although EA is associated with superior hemodynamic
      status, reduced duration of operation, less health care cost, and lower rate of
      surgical complications when compared with GA. Controversy still exists with
      regard to the optimum choice of anesthesia for major lumbar spine surgery,
      especially in elderly patients. MATERIALS AND METHODS: From September 2016 to
      August 2017, consecutive patients aged 70 years or older who underwent lower
      lumbar fusion surgery with EA or GA were enrolled in the study. Recorded data for
      all patients included: age, sex, medical conditions; surgical time, operation
      procedure, blood loss; intraoperative hypertension and tachycardia; occurrence of
      nausea, vomiting, delirium, or cardiopulmonary complications. Postoperative pain
      and satisfaction were also assessed. RESULTS: A total of 89 patients were
      included. Of these, 42 patients underwent GA and 47 patients underwent EA. The
      number of patients experiencing hypertension and tachycardia during anesthesia
      was significantly increased in the GA group when compared with EA. Patients with
      EA had significantly less delirium, nausea, and vomiting. The average Visual
      Analog Scale scores were significantly higher in the GA group at 0-8 hours after
      surgery. Patients underwent EA were more satisfied than patients with GA.
      CONCLUSIONS: There was an association between those who received EA and superior
      perioperative outcomes. However, some concerns including airway security,
      operation duration, and obesity, must be carefully evaluated. In addition, it
      should be noted that this study was retrospective and selection bias may probably
      exist which may interfere with the results.

PMID- 30222621
TI  - Risk Factors for a Long Hospital Stay Following Minimally Invasive Lumbar
      Discectomy.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The purpose of the study was
      to determine risk factors for discharge after postoperative day (POD) 0 in
      patients undergoing 1-level minimally invasive lumbar discectomy (MIS LD).
      SUMMARY OF BACKGROUND DATA: MIS LD has proven to be an effective treatment
      modality for low back pain and radiculopathy associated with intervertebral disc
      herniations. With increasing focus on cost reduction and value-based care,
      minimization of postoperative length of stay has become an important topic for
      physicians and hospital administrators. METHODS: A prospectively maintained
      surgical database of patients who underwent 1-level MIS LD by a single surgeon
      from 2011 to 2016 was reviewed. Long length of stay was defined as discharge
      after POD 0. Bivariate and stepwise multivariate Poisson regression with robust
      error variance was used to determine risk factors for discharge after POD 0.
      Variables analyzed included patient demographics, comorbidities, operative
      characteristics, preoperative pain scores, postoperative inpatient pain scores,
      and postoperative narcotics consumption. RESULTS: A total of 176 patients were
      included; 9.7% of included patients were discharged on POD 1 or later. On
      bivariate analysis, diabetic status (57.1% vs. 7.7%; relative risk [RR]=7.43;
      P<0.01) and narcotic consumption <6.00 oral morphine equivalents/h (13.1% vs.
      1.2%; RR=11.11; P=0.019) were associated with a prolonged length of stay. On
      stepwise multivariate analysis, diabetic status (RR=10.5; 95% confidence
      interval, 3.60-30.98; P<0.001) was found to be independently associated with a
      prolonged length of stay after MIS LD. CONCLUSIONS: The results indicate that
      diabetic status is an independent risk factor for increased LOS following single
      level MIS LD. Delayed hospital discharge can lead to increased costs, increased
      risk of complications, and decreased patient satisfaction. Thus, providers can
      use this information to better counsel diabetic patients and monitor them more
      closely following MIS LD. Additional work must be done to better understand risk
      factors for increased length of stay following MIS LD in procedure-specific
      populations. LEVEL OF EVIDENCE: Level II.

PMID- 30222622
TI  - The Effect of Preoperative Symptom Duration on Postoperative Outcomes After a
      Tubular Lumbar Microdiscectomy.
AB  - STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: This study aims to
      characterize the effect of preoperative symptom duration on postoperative
      outcomes after minimally invasive lumbar microdiscectomy (MIS LD). SUMMARY OF
      BACKGROUND DATA: It is unknown whether extended nonoperative treatment before MIS
      LD has implications for long-term clinical outcomes even after surgery is
      performed. MATERIALS AND METHODS: A prospectively maintained surgical registry of
      patients undergoing MIS LD by a single surgeon between 2013 and 2017 was
      reviewed. Preoperative symptom duration was dichotomized into 2 groups (<=6 and
      >6 mo). Only patients with full clinical data at 6 months postoperative follow-up
      were included in the study. Clinical outcomes were assessed at 6, 12 weeks, and 6
      months after surgery. The number of patients obtaining a minimum clinically
      important difference was assessed. Groups were compared with the chi analysis and
      the student t tests for categorical and continuous data, respectively. RESULTS:
      In total, 94 patients were identified. A total of 45 patients (47.9%) had symptom
      duration <=6 months. No differences in baseline characteristics were found
      (P>0.05). Patients with shorter symptom duration had significantly greater
      improvement in Oswestry Disability Index scores at 6 weeks (P=0.004), 12 weeks
      (P=0.022), and 6 months (P=0.005). Patients with shorter duration of symptoms
      also obtained minimum clinically important difference for Oswestry Disability
      Index at a greater rate than those with longer duration of symptoms (P=0.015).
      CONCLUSIONS: Although patients who underwent MIS LD within 6 months of symptom
      onset had similar baseline characteristics compared with patients who underwent
      surgery after 6 months of symptoms, the patients with longer preoperative symptom
      duration had worse functional outcomes at 6 months after surgery. These results
      suggest that earlier MIS lumbar microdiscectomy may provide a functional benefit
      for patients. Further studies should therefore evaluate the efficacy of
      nonoperative treatment in the setting of lumbar herniated nucleus pulposus, as
      prolonged conservative management may potentially impair functional recovery
      after surgery.

PMID- 30222624
TI  - High rate of inappropriate referrals to pediatric orthopedics in an egalitarian
      healthcare system.
AB  - Previous studies have shown relatively high rates of inappropriate referrals to
      pediatric orthopedic surgery. The purpose of this study was to determine the rate
      of inappropriate referrals in an egalitarian healthcare system. We reviewed all
      400 referrals to our pediatric orthopedic surgery practice over a 2-year period
      and assessed the appropriateness of each based on the American Academy of
      Pediatrics guidelines. A total 206 (52%) referrals were deemed appropriate. There
      is a high rate of inappropriate referral to pediatric orthopedic surgery even
      within a closed, egalitarian healthcare system. Targeted education of primary
      care providers may help reduce this rate.

PMID- 30222623
TI  - Effect of Cervical Decompression Surgery on Gait in Adult Cervical Spondylotic
      Myelopathy Patients.
AB  - STUDY DESIGN: This is a prospective cohort study. OBJECTIVE: To evaluate the
      effect of cervical decompression surgery on the biomechanics of the spine and
      lower extremities in cervical spondylotic myelopathy (CSM) patients and compare
      with asymptomatic controls. SUMMARY OF BACKGROUND DATA: Difficulties with balance
      and gait are one of the most common manifestations of CSM. Patients with CSM have
      a slower gait speed, prolonged double support duration, and reduced cadence
      compared with healthy controls. Surgical decompression was found to improve
      clinical outcomes, but conflicting results are noted when examining function.
      MATERIALS AND METHODS: In total, 25 subjects with symptomatic CSM underwent
      clinical gait analysis performed a week before (pre) and 3 months after the
      surgery (post). Clinical gait analysis was performed on 30 matched asymptomatic
      controls as well. Spine and lower extremity kinematics, spatiotemporal
      parameters, and clinical outcome were measured. RESULTS: CSM patients
      demonstrated slower walking speed (P=0.006), reduced cadence (P=0.001), longer
      step time (P=0.013) wider step width (P=0.001), greater ankle range of motion
      (ROM) (P=0.019), less hip ROM (P=0.050), increased pelvis (P=0.001), and lumbar
      spine (P=0.049) ROM compared with controls. Postoperatively CSM patients
      demonstrated a faster walking speed (P=0.002), increased cadence (P=0.029),
      longer step length (P=0.015), narrower step width (P=0.004), greater knee
      (P=0.043), and hip ROM (P=0.007), less pelvis (P=0.002), lumbar spine (P=0.035),
      and cervical spine (P=0.044) ROM, and improved clinical outcomes (neck pain
      disability index questionnaire, oswestry disability index, and visual analog
      scale; P=0.001) compared with their preoperative values. Postsurgical CSM
      patients did not present with any differences compared with controls, beside
      pelvis ROM (P=0.019). CONCLUSIONS: Preoperatively, CSM patients clearly showed
      altered gait parameters compared with controls. However, after cervical
      decompression surgery, CSM patients exhibited improved gait pattern,
      spatiotemporal parameters, spine and lower extremity ROM, as well as patient
      reported outcomes. Postoperatively, CSM patients did not show major differences
      in gait when compared with matched asymptomatic controls.

PMID- 30222625
TI  - Nonoperative versus operative treatment for displaced midshaft clavicle fractures
      in adolescents: a comparative study.
AB  - We aimed to compare the outcomes and complications of nonoperative and operative
      treatment for displaced midshaft clavicle fractures in adolescents. Radiological
      and functional evaluations and complications for 23 patients with nonoperative
      treatment were compared with those for 18 patients with operative treatment. No
      nonunion developed in either group. No significant intergroup differences were
      observed for occurrence of delayed union or time to union (P=0.851 and 0.887,
      respectively). Both groups showed excellent functional outcomes on the basis of
      Disabilities of the Arm, Shoulder and Hand scores and Constant Shoulder Scores.
      Shoulder abduction strength and range of motion were also well restored in both
      treatment groups. However, recovery of shoulder range of motion was significantly
      faster in the operative group (mean: 5.3 weeks; range: 4.0-7.0 weeks) than in the
      nonoperative group (mean: 9.9 weeks; range: 8.0-19.0 weeks) (P<0.001). There were
      no patients in either treatment group who needed revisional surgery to address
      complications with functional deficits. Both nonoperative and operative
      treatments yielded excellent outcomes, without severe complications. On the basis
      of our results, nonoperative treatment is recommended as a primary treatment
      option for displaced midshaft clavicle fractures in adolescents. However,
      operative treatment can be considered in selected patients who require early
      functional recovery or have a high activity level.

PMID- 30222626
TI  - Drug-Induced Cutaneous Lupus Erythematosus: A Case Series of Five Patients with
      Bupropion-Associated Disease.

PMID- 30222627
TI  - Spinal Cord Injury Secondary to Eosinophilic Granulomatosis With Polyangiitis:
      Case Report and Review of the Literature.

PMID- 30222628
TI  - Spinal Tophi Causing Cord Compression and Mimicking Epidural Abscess in a Young
      Man With Lesch-Nyhan Variant.

PMID- 30222629
TI  - Nonuremic Calciphylaxis.

PMID- 30222630
TI  - Pancreatic adenocarcinoma with histologically proven portal vein infiltration:
      what is the outcome?
AB  - OBJECTIVES: Technical feasibility and safety of portal vein (PV) and superior
      mesenteric vein (SMV) resection during pancreaticoduodenectomy (PD) for cancer
      has been confirmed, but oncological benefits remain unclear. The present study
      aimed to explore the long-term outcomes of PD with PV/SMV resection and proven
      histologically invasion. PATIENTS AND METHODS: A total of 95 consecutive PD were
      performed between January 2008 and August 2013, and 29 patients underwent PV/SMV
      resection with histologically proven venous tumor infiltration. Patients were
      matched 1 : 1 to controls who did not undergo venous resection, based on
      demographic and tumor characteristics. RESULTS: Disease-free survival (DFS) of
      the PV/SMV invasion group and control group was 9.5 and 7.6 months, respectively
      (P=0.51). Median survival and survival at 1, 3, and 5 years were 12.9 months, 59,
      17, and 10%, respectively, in case of PV/SMV invasion compared with 20.3 months,
      72, 31, and 10%, respectively in control group (P=0.13). Patients with complete
      transmural infiltration presented nonsignificantly shorter DFS (9.0 months)
      compared with those with partial venous wall infiltration (18.4 months, P=0.78).
      CONCLUSION: Histologically proven portal venous invasion in patients undergoing
      PD for adenocarcinoma seemed not to have an effect on both DFS and overall long
      term survival.

PMID- 30222631
TI  - Vitamin D to Prevent Lung Injury Following Esophagectomy-A Randomized, Placebo
      Controlled Trial.
AB  - OBJECTIVES: Observational studies suggest an association between vitamin D
      deficiency and adverse outcomes of critical illness and identify it as a
      potential risk factor for the development of lung injury. To determine whether
      preoperative administration of oral high-dose cholecalciferol ameliorates early
      acute lung injury postoperatively in adults undergoing elective esophagectomy.
      DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Three
      large U.K. university hospitals. PATIENTS: Seventy-nine adult patients undergoing
      elective esophagectomy were randomized. INTERVENTIONS: A single oral preoperative
      (3-14 d) dose of 7.5 mg (300,000 IU; 15 mL) cholecalciferol or matched placebo.
      MEASUREMENTS AND MAIN RESULTS: Primary outcome was change in extravascular lung
      water index at the end of esophagectomy. Secondary outcomes included PaO2:FIO2
      ratio, development of lung injury, ventilator and organ-failure free days, 28 and
      90 day survival, safety of cholecalciferol supplementation, plasma vitamin D
      status (25(OH)D, 1,25(OH)2D, and vitamin D-binding protein), pulmonary vascular
      permeability index, and extravascular lung water index day 1 postoperatively. An
      exploratory study measured biomarkers of alveolar-capillary inflammation and
      injury. Forty patients were randomized to cholecalciferol and 39 to placebo.
      There was no significant change in extravascular lung water index at the end of
      the operation between treatment groups (placebo median 1.0 [interquartile range,
      0.4-1.8] vs cholecalciferol median 0.4 mL/kg [interquartile range, 0.4-1.2
      mL/kg]; p = 0.059). Median pulmonary vascular permeability index values were
      significantly lower in the cholecalciferol treatment group (placebo 0.4
      [interquartile range, 0-0.7] vs cholecalciferol 0.1 [interquartile range, -0.15
      to -0.35]; p = 0.027). Cholecalciferol treatment effectively increased 25(OH)D
      concentrations, but surgery resulted in a decrease in 25(OH)D concentrations at
      day 3 in both arms. There was no difference in clinical outcomes. CONCLUSIONS:
      High-dose preoperative treatment with oral cholecalciferol was effective at
      increasing 25(OH)D concentrations and reduced changes in postoperative pulmonary
      vascular permeability index, but not extravascular lung water index.

PMID- 30222632
TI  - Early Enteral Nutrition Reduces Mortality and Improves Other Key Outcomes in
      Patients With Major Burn Injury: A Meta-Analysis of Randomized Controlled Trials.
AB  - OBJECTIVES: To identify, appraise, and synthesize current evidence to determine
      whether early enteral nutrition alters patient outcomes from major burn injury.
      DATA SOURCES: Medline, Embase, and the China National Knowledge Infrastructure
      were searched. The close out date was May 1, 2018. STUDY SELECTION: Early enteral
      nutrition was defined as a standard formula commenced within 24 hours of injury
      or admission to ICU or burn unit. Comparators included any form of nutrition
      support "except" early enteral nutrition. Only randomized controlled trials
      reporting patient-centered outcomes were eligible for inclusion. DATA EXTRACTION:
      The primary outcome was mortality. Gastrointestinal hemorrhage, sepsis,
      pneumonia, renal failure, and hospital stay were evaluated as secondary outcomes.
      DATA SYNTHESIS: Nine-hundred fifty-eight full-text articles were retrieved and
      screened. Seven randomized controlled trials enrolling 527 participants with
      major burn injury were included. Compared with all other types of nutrition
      support, early enteral nutrition significantly reduced mortality (odds ratio,
      0.36; 95% CI, 0.18-0.72; p = 0.003; I = 0%). Early enteral nutrition also
      significantly reduced gastrointestinal hemorrhage (odds ratio, 0.21; 95% CI, 0.09
      0.51; p = 0.0005; I = 0%), sepsis (odds ratio, 0.23; 95% CI, 0.11-0.48; p <
      0.0001; I = 0%), pneumonia (odds ratio, 0.41; 95% CI, 0.21-0.81; p = 0.01; I =
      63%), renal failure (odds ratio, 0.27; 95% CI, 0.09-0.82; p = 0.02; I = 32%), and
      duration of hospital stay (-15.31 d; 95% CI, -20.43 to -10.20; p < 0.00001; I =
      0%). CONCLUSIONS: The improvements in clinical outcomes demonstrated in this meta
      analysis are consistent with the physiologic rationale cited to support clinical
      recommendations for early enteral nutrition made by major clinical practice
      guidelines: gut integrity is preserved leading to fewer gastrointestinal
      hemorrhages, less infectious complications, a reduction in consequent organ
      failures, and a reduction in the onset of sepsis. The cumulative benefit of these
      effects improves patient survival and reduces hospital length of stay.

PMID- 30222633
TI  - Opioid Use After ICU Admission Among Elderly Chronic Opioid Users in Ontario: A
      Population-Based Cohort Study.
AB  - OBJECTIVES: Critical illness is often associated with painful procedures and
      prolonged opioid infusions, raising the concern that chronic opioid users may be
      exposed to escalating doses that are continued after hospital discharge. We
      sought to assess patterns of opioid use after intensive care among elderly
      patients identified as chronic opioid users prior to hospitalization. DESIGN:
      Population-based cohort study. SETTING: All adult ICUs in the province of
      Ontario, Canada. PARTICIPANTS: Elderly patients (> 65 yr) admitted to ICUs
      between April 2002 and March 2015 who also survived to day 180 after hospital
      discharge, identified as chronic opioid users prior to hospitalization. EXPOSURE:
      Chronic opioid use in the year before hospital admission, as well as a filled
      opioid prescription with a duration covering the day of hospital admission.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion of patients
      who filled an opioid prescription with a duration covering day 180 after hospital
      discharge; secondary outcome was the difference in morphine equivalent daily
      dosage at day 180 after discharge compared with the amount prescribed prior to
      hospital admission. Of 496,985 elderly admissions to ICUs, 19,584 (3.9%) were
      chronic opioid users before hospitalization who also survived to day 180 after
      hospital discharge. The median daily dose of opioid prescriptions filled before
      hospital admission was 32.1 mg morphine equivalent (interquartile range, 17.5
      75.0 mg morphine equivalent). Among these survivors, 63.3% had at least one
      opioid prescription filled with a duration covering day 180; 22.0% had filled
      prescriptions for a higher daily morphine equivalent dose compared with
      prehospitalization, 19.8% were unchanged, 21.5% had a lower dose, and 36.7% had
      no prescription filled. The majority of reduction was in prescriptions for
      codeine and oxycodone. CONCLUSIONS: Among chronic opioid users, hospitalization
      with critical illness was not associated with substantial increases in opioids
      prescribed in the 6 months following hospitalization.

PMID- 30222635
TI  - Magnitude and Pace of Improvement in Performance of Hospitals Treating
      Mechanically Ventilated Children in the United States: Analysis From Two National
      Databases.
AB  - OBJECTIVES: To use two national databases to quantify the pace and magnitude of
      improvement in hospital performance (as measured by mortality) across hospitals
      caring for critically ill children in the United States. DESIGN: We used
      empirical Bayes shrinkage estimators to obtain shrinkage estimators of
      observed/expected mortality ratios for each hospital assuming a Gamma Poisson
      posterior distribution. Revised mortality rates for each hospital were obtained
      from the shrunken incidence ratios. SETTING: Pediatric Health Information System
      participating hospital and Kids' Inpatient Database participating hospital.
      PATIENTS: Patients less than or equal to 18 years old who received invasive
      mechanical ventilation during their hospital stay at a Pediatric Health
      Information System participating hospital (2005-2015) or a Kids' Inpatient
      Database participating hospital (1997-2012) were included. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: A total of 486,838 patients from 48 Pediatric
      Health Information System hospitals and 798,840 patients from 947 Kids' Inpatient
      Database hospitals were included. For the Pediatric Health Information System
      hospitals, the median shrunken adjusted mortality decreased from 11.66% in 2005
      to 7.11% in 2015; for the Kids' Inpatient Database hospitals, it decreased from
      5.79% in 1997 to 3.86% in 2012. By 2015, more than 95% of the Pediatric Health
      Information System hospitals performed better than or as well as the best 25% of
      the hospitals in 2005. By 2012, 33.7% of Kids' Inpatient Database hospitals
      performed better than or as well as the best 25% of the hospitals in 1997.
      CONCLUSIONS: This study provides insight into the magnitude of improvement in
      patient mortality in hospitals caring for critically ill children in the United
      States. This study quantifies hospital performance in pediatric critical care
      over time, and it provides benchmarks against which individual hospitals can
      assess their own performance. In future pediatric epidemiologic studies, we
      should identify outcomes other than mortality to quantify improvement in hospital
      performance.

PMID- 30222634
TI  - A Systematic Review and Meta-Analysis Examining the Impact of Sleep Disturbance
      on Postoperative Delirium.
AB  - OBJECTIVES: Basic science and clinical studies suggest that sleep disturbance may
      be a modifiable risk factor for postoperative delirium. We aimed to assess the
      association between preoperative sleep disturbance and postoperative delirium.
      DATA SOURCES: We searched PubMed, Embase, CINAHL, Web of Science, and Cochrane
      from inception until May 31, 2017. STUDY SELECTION: We performed a systematic
      search of the literature for all studies that reported on sleep disruption and
      postoperative delirium excluding cross-sectional studies, case reports, and
      studies not reported in English language. DATA EXTRACTION: Two authors
      independently performed study selection and data extraction. We calculated pooled
      effects estimates with a random-effects model constructed in Stata and evaluated
      the risk of bias by formal testing (Stata Corp V.14, College Station, TX), DATA
      SYNTHESIS:: We included 12 studies, from 1,238 citations that met our inclusion
      criteria. The pooled odds ratio for the association between sleep disturbance and
      postoperative delirium was 5.24 (95% CI, 3.61-7.60; p < 0.001 and I = 0.0%; p =
      0.76). The pooled risk ratio for the association between sleep disturbance and
      postoperative delirium in prospective studies (n = 6) was 2.90 (95% CI, 2.28
      3.69; p < 0.001 and I = 0.0%; p = 0.89). The odds ratio associated with
      obstructive sleep apnea and unspecified types of sleep disorder were 4.75 (95%
      CI, 2.65-8.54; p < 0.001 and I = 0.0%; p = 0.85) and 5.60 (95% CI, 3.46-9.07; p <
      0.001 and I = 0.0%; p = 0.41), respectively. We performed Begg's and Egger's
      tests for publication bias and confirmed a null result for publication bias (p =
      0.371 and 0.103, respectively). CONCLUSIONS: Preexisting sleep disturbances are
      likely associated with postoperative delirium. Whether system-level initiatives
      targeting patients with preoperative sleep disturbance may help reduce the
      prevalence, morbidity, and healthcare costs associated with postoperative
      delirium remains to be determined.

PMID- 30222636
TI  - Risk Factors for Persistent Cognitive Impairment After Critical Illness, Nested
      Case-Control Study.
AB  - OBJECTIVES: Persistent cognitive impairment after critical illness is an
      important healthcare problem forecasted to worsen in the near future. However,
      the epidemiology is insufficiently explored. We aimed to determine potentially
      modifiable risk factors during ICU hospitalization that play a significant role
      in developing persistent cognitive impairment. DESIGN: An observational case
      control study. SETTINGS: Mayo Clinic ICUs between July 1, 2004, and November 20,
      2015. PATIENTS: We conducted a study nested in a large cohort of 98,227 adult
      critically ill patients. Using previously validated computable phenotypes for
      dementia and cognitive impairment, we determined the onset of cognitive
      impairment relative to ICU hospitalization and associated risk factors. The
      primary endpoint of the study was new and persistent cognitive impairment
      documented between 3 and 24 months after ICU discharge. INTERVENTIONS: Unadjusted
      and adjusted analyses were performed to identify potentially modifiable risk
      factors during ICU hospitalization. MEASUREMENTS AND MAIN RESULTS: Among 21,923
      unique patients identified as cognitively impaired (22% of the entire ICU
      cohort), 2,428 (2.5%) developed incident new and persistent cognitive dysfunction
      after the index ICU admission. Compared with age- and sex-matched ICU controls
      (2,401 pairs), cases had higher chronic illness burden (Charlson Comorbidity
      Index, 6.2 vs 5.1; p < 0.01), and were more likely to have multiple ICU stays
      (22% vs 14%; p < 0.01). After adjustment for baseline differences, new and
      persistent cognitive dysfunction was associated with higher frequency of acute
      brain failure in the ICU, a higher exposure to severe hypotension, hypoxemia,
      hyperthermia, fluctuations in serum glucose, and treatment with quinolones or
      vancomycin. Association with sepsis observed in univariate analysis did not
      persist after adjustment. CONCLUSIONS: Cognitive dysfunction is highly prevalent
      in ICU patients. Incident new and persistent cognitive impairment is less common
      but important, potentially preventable problem after critical illness. Chronic
      comorbidities and number of ICU stays increase the risk of post-ICU cognitive
      dysfunction irrespective of age. Modifiable ICU exposures were identified as
      potential targets for future prevention trials.

PMID- 30222638
TI  - Triphasic Waves and Encephalopathy in the Setting of Pregabalin Toxicity.
AB  - EEG triphasic waves are usually seen in the setting of metabolic
      encephalopathies, but may also occur secondary to medication toxicity. There are
      few reports of medications causing continuous triphasic waves, and only rare
      reports in the literature show an association between these discharges and
      pregabalin toxicity. Here, we describe triphasic waves in a patient with
      underlying white matter lesions, as well as pregabalin toxicity, secondary to
      renal insufficiency. Patients with renal or hepatic failure presenting with
      triphasic waves and confusion pose a diagnostic challenge in determining whether
      the etiology of their encephalopathy is purely metabolic or whether it results
      from impaired medication clearance and subsequent toxicity. In this patient,
      discontinuing pregabalin improved her EEG despite the ongoing renal
      insufficiency, confirming pregabalin toxicity as an etiology of triphasic waves
      and encephalopathy.

PMID- 30222637
TI  - Prospective Multicenter Clinical Trial of a Temperature-Controlled Subcutaneous
      Microneedle Fractional Bipolar Radiofrequency System for the Treatment of
      Cellulite.
AB  - BACKGROUND: A bipolar fractional radiofrequency (RF) device was developed to
      generate cutaneous thermal injuries using a temperature-controlled microneedle
      electrode array. OBJECTIVE: Evaluate safety and efficacy of a novel subcutaneous
      microneedle RF for treatment of posterolateral thigh cellulite. METHODS: The
      study design was an institutional review board-approved multicenter clinical
      trial after a per-protocol analysis. Fifty subjects with Nurnberger-Muller Grade
      II or III cellulite were enrolled at 4 treatment centers and received 1
      subcutaneous microneedle RF treatment (67 degrees C/4-second duration). Efficacy
      was evaluated by blinded grading by 3 dermatologists using randomized,
      standardized photographs and investigator grading at baseline, 1-, 3-, and 6
      month follow-up. As per the Food and Drug Administration, treatment success was
      defined by >=1-point improvement on dimple number or severity of undulation
      irregularities scales by at least 2 of 3 blinded physicians. Study subjects' self
      assessments and satisfaction questionnaires and procedural pain levels and
      adverse events were monitored. RESULTS: Blinded physician evaluations revealed a
      procedural success rate of 93% at 6-month follow-up. Procedural pain level was
      3.74 +/- 1.96 on a 10-point scale. There were no adverse events. Seventy-five
      percent of subjects were satisfied with the results at 6-month follow-up.
      CONCLUSION: The results indicate that subcutaneous microneedle RF treatment is
      safe and effective for long-term treatment of Type II and III cellulite in a
      single session.

PMID- 30222639
TI  - Removal of Metaphyseal Screw Only After Hemiepiphysiodesis Correction of Coronal
      Plane Deformities Around the Knee Joint: Is This a Safe and Advisable Strategy?
AB  - PURPOSE: Correcting lower limb angular deformities in the skeletally immature
      patient with guided growth is a very common procedure. Using an 8-plate construct
      to produce reversible hemiepiphysiodesis allows correction of the mechanical axis
      of the limb. It has become routine strategy to remove only the metaphyseal screw
      from the 8-plate construct after desired correction is achieved, in order to ease
      its reinsertion in case of deformity recurrence. In this study, we evaluated the
      efficacy and safety of this technique. METHODS: We reviewed the results of 80
      patients (133 limbs) who were treated by guided growth using 8-plate
      hemiephisiodesis around the knee. After achievement of the correction goal, both
      screws and plate were removed in 78 limbs while only the metaphyseal screw was
      removed in 55 limbs. RESULTS: The mean age of patient was 8.9 years at the time
      of surgery. Within the group whose metaphyseal screw was removed, 12 limbs showed
      radiographic signs of deformity recurrence and underwent reinsertion of the
      metaphyseal screw. In 9 of the cases of metaphyseal screw reinsertion, the plate
      or its location had to be changed (mean follow-up after screw removal was 14 mo).
      There were 2 cases where leaving the plate with an epiphyseal screw caused a
      radiographic bone bar and undesired clinical growth arrest. CONCLUSIONS: On the
      basis of our experience, leaving the 8-plate construct with an epiphyseal screw
      in place exposes the patient to risks of bony bar, growth arrest, and an
      additional surgery for hardware removal. The majority of 8-plate constructs are
      not suitable for reinsertion of the metaphyseal screw.

PMID- 30222640
TI  - Myelodysplastic syndromes in children.
AB  - PURPOSE OF REVIEW: Myelodysplastic syndromes (MDSs) are rare disorders in
      children, showing peculiar clinical manifestations and biological features. This
      review will summarize biological, genetic and clinical features of childhood MDS
      and will provide an update of the algorithm of treatment of the different disease
      variants. RECENT FINDINGS: The most recent classification of MDS includes
      refractory cytopenia of childhood (RCC), advanced and therapy-related MDS.
      Importantly, in children, these clonal hematopoietic disorders may be often
      associated with inherited bone marrow failure syndromes, this representing a
      challenge for diagnostic work-up and treatment. Moreover, germline syndromes
      predisposing to develop MDS/acute myeloid leukemia have been recently identified,
      such as those caused by mutations in GATA2, ETV6, SRP72 and SAMD9/SAMD9-L.
      SUMMARY: Treatment of childhood MDS varies according to specific disease
      features; allogeneic hematopoietic stem cell transplantation (HSCT) using a Human
      Leukocyte antigen (HLA)-identical donor, whenever available, represents the
      treatment of choice for most of these children. HSCT is indicated in MDS with
      excess of blasts, or in therapy-related MDS. For RCC patients, HSCT is
      recommended for RCC associated with monosomy 7, or complex karyotype and for
      patients showing severe neutropenia or transfusion dependence. Novel approaches
      of HSCT from an HLA-haploidentical relative after selective graft manipulation
      allow reducing transplant-related complications.

PMID- 30222641
TI  - Allogeneic stem cell transplantation from unrelated donors in acute leukaemia.
AB  - PURPOSE OF REVIEW: To summarize the past and current knowledge of the use of
      unrelated donors (URDs) in allogeneic stem cell transplantation for patients with
      acute leukaemia. RECENT FINDINGS: The outcome of URD stem cell transplants in
      terms of treatment-related mortality, relapse rates, disease free survival and
      overall survival is comparable to sibling donors. SUMMARY: Haematopoietic stem
      cell transplantation (HSCT) is the therapy of choice in many haematological
      malignant diseases but only one-third of the patients will have an HLA-matched
      sibling. The possibility of finding a matched URD is more than 70% because of
      recent advances in HLA typing and continuous expansion of URD registries around
      the world. The use of URD as a source of stem cells in adult patients are
      steadily increasing and in the last 8 years, superseded the matched sibling
      donors and became the most commonly used stem cell source. There is also an
      increasing trend of using peripheral blood stem cells than bone marrow stem
      cells. Outcomes following URD transplants depend mainly upon the indication and
      urgency of transplant, age and comorbidities of recipients, cytomegalovirus
      matching/mismatching between donor and the recipient and degree of HLA matching.

PMID- 30222642
TI  - Early Testing of Serum Ferritin Facilitates Hemophagocytic Lymphohistiocytosis
      Diagnosis in Children.
AB  - The clinical and laboratory features of hemophagocytic lymphohistiocytosis (HLH)
      are nonspecific that makes the definitive diagnosis of HLH very challenging. The
      disease is almost universally fatal in the absence of early recognition and
      appropriate therapy. Elevated serum ferritin level is one of the diagnostic
      markers of HLH disease. We report the value of testing serum ferritin level early
      in the disease process in 3 pediatric patients who presented with persistent
      fever and sepsis-like features. Detection of elevated serum ferritin levels
      facilitated further testing to confirm the diagnosis of HLH and initiate early
      therapy with good outcomes.

PMID- 30222643
TI  - Bowel Preparation With Polyethylene Glycol 3350 or Fasting Only Before Peroral
      Single-balloon Enteroscopy: A Randomized European Multicenter Trial.
AB  - BACKGROUND: Although bowel preparation before colonoscopy and capsule endoscopy
      is widely evaluated and usually follows established guidelines, a standard
      preparation regime for peroral small bowel enteroscopy is yet to be defined.The
      aim of the present study was to compare small bowel preparation with polyethylene
      glycol (PEG) and "fasting only" (FO) before peroral single-balloon enteroscopy
      (SBE). STUDY: We compared small bowel preparation with PEG versus "FO" for
      peroral SBE in a randomized European multicenter trial. Patients' and procedural
      characteristics were documented and carefully analyzed. Primary endpoint was the
      oral intubation depth of the small bowel. A modified Boston preparation scale was
      used to assess bowel cleansing as a secondary endpoint. RESULTS: In total, 43
      patients were enrolled in this study (FO group: n=25; PEG group: n=18). In both
      groups, patients' characteristics were comparable. The indications for oral
      enteroscopy were equally distributed in both groups (P=0.894). The oral
      intubation depth was significantly higher in the PEG versus the FO group (261+/
      87 vs. 203+/-66 cm; P=0.019; mean+/-SD), while the quality of bowel preparation
      was equally sufficient in both groups [complete visualization of the mucosa
      (Boston preparation scale) 83% versus 76% (P=1.000)]. CONCLUSIONS: Small bowel
      preparation with PEG for SBE yields significantly deeper intubation as compared
      with "FO" preparation. As patient comfort and safety was similar in both groups,
      PEG preparation might be favored, especially if deep intubation of the small
      bowel is desired. For patients requiring visualization of the proximal jejunum, a
      FO preparation seems to be sufficient.

PMID- 30222644
TI  - Individual and Geospatial Characteristics Associated With Use and Nonuse of the
      Fecal Immunochemical Test (FIT) for Colorectal Cancer Screening in an Urban
      Minority Population.
AB  - PURPOSE: Initiatives by the Centers for Disease Control and Prevention as well as
      the National Colorectal Cancer Roundtable aim to increase the rate of colorectal
      cancer (CRC) screening. We assess individual and geographic characteristics
      associated fecal immunochemical test (FIT) CRC screening over 3 years. METHODS:
      This is a retrospective study of 1500 FIT kits which were mailed or
      opportunistically handed to eligible participants in Brooklyn, New York from
      January 2014 to December 2016. Eligibility criteria included increased risk for
      colon cancer, uninsured or underinsured, and a minimum age of 50 years to warrant
      CRC screening. We looked at the association of individual demographic
      characteristics and FIT screening by logistic regression using SPPS version 23
      software. In addition, using ArcGIS, we coded patients address and layered census
      tract population information to find associations. RESULTS: In total, 1367 Cancer
      Services Participants met our study criteria. The study sample was predominantly
      female (95.2%) and minority (46% African American, 24.7% Hispanic, 17.3%
      Caucasian, 11.4% Asian) and on average 59 years old (SD, 5.7). A large majority
      (73%) had household incomes below $20,000/year. Approximately half (49.9%) of all
      Cancer Services Participants returned their FIT kit. In participants who did not
      return their FIT kit, the majority were African American (41%), followed by
      Hispanics (26.5%), Caucasians (20.6%), and Asians (11.8%). Multivariable logistic
      regression showed that a screening history of prior colonoscopy or FIT, gender,
      ethnicity, and educational attainment were significantly associated with FIT CRC
      screening uptake (P<0.05). Geospatial mapping showed clusters of low screening
      uptake in areas of high poverty. Hot-spot analysis identified areas of
      significant vulnerability. CONCLUSIONS: FIT uptake remains suboptimal. Individual
      predictors as well as area poverty is associated with low screening uptake.
      Geospatial mapping is an effective tool for evaluating CRC screening uptake.

PMID- 30222645
TI  - Globus: Current Concepts and Dilemmas.
AB  - Globus is an area of interest for many medical specialists including
      otorhinolaryngologists, gastroenterologist, allergists, and psychiatrists. It may
      be caused by an organic disease, but it is not uncommon that an underlying
      etiology remains unidentified even after a full workup has been performed.
      Patients who suffer from globus usually visit several physicians from different
      specialties without finding a solution for their symptoms. Identifying the
      underlying cause of globus is not always a simple task; therefore, structural or
      functional abnormalities of the thyroid, larynx, pharynx, and esophagus should be
      investigated. Gastroesophageal reflux disease is commonly considered to be the
      underlying cause after being identified in an otorhinolarygeal (ear, nose, and
      throat) evaluation, which is usually the first diagnostic step. In the last few
      years, an inlet patch in the proximal esophagus has been shown to be associated
      with globus, and its elimination has resulted in symptom resolution in some
      patients. Finally, globus can be associated with psychiatric disorders as well as
      oropharyngeal hypersensitivity that could be either chemical or mechanical.
      Treatment is directed toward an identified organic cause; in those with a
      functional disorder, the mainstay of therapy includes neuromodulators and
      psychiatric/psychological interventions.

PMID- 30222646
TI  - Has Rotavirus Vaccination Decreased the Prevalence of Biliary Atresia?
AB  - OBJECTIVES: Biliary atresia (BA) is a rare neonatal liver disease that causes
      cholestasis and is the leading indication for pediatric liver transplantation.
      Although the exact etiology of BA remains unknown, evidence from murine models
      supports the role of rotavirus infection in the development of BA. In 2006,
      universal rotavirus vaccination was implemented in the United States. The goal of
      this study was to determine if the prevalence of BA correlated with the number of
      annual rotavirus infections. METHODS: We utilized data from the 1997 to 2012
      Kids' Inpatient Database and the 1988 to 2015 Organ Procurement and
      Transplantation Network to determine the annual number of infant discharges with
      a primary diagnosis of BA and the number of infants with BA who received a liver
      transplant, respectively. We obtained the number of annual rotavirus infections
      from the National Respiratory and Enteric Virus Surveillance System and examined
      whether trends existed between the data from these 3 sources over time. RESULTS:
      From 1997 to 2006, the number of positive rotavirus antigen tests remained
      steady, however a rapid decrease was observed from 2006 to 2012 (8774 to 1277),
      coinciding with the uptake of rotavirus immunizations nationwide. The number of
      BA discharges doubled from 1997 to 2003 and again increased from 2006 to 2012 (67
      to 137 and 117 to 156), while the number of liver transplants for BA changed very
      little from 1997 to 2012. CONCLUSIONS: The recent implementation of rotavirus
      vaccination has not had any substantial influence on the prevalence of BA in the
      United States.

PMID- 30222647
TI  - Tomoelastography Paired With T2* Magnetic Resonance Imaging Detects Lupus
      Nephritis With Normal Renal Function.
AB  - OBJECTIVES: The aim of this study was to test multiparametric magnetic resonance
      imaging including blood oxygen level-dependent (BOLD) imaging by T2* mapping,
      magnetic resonance elastography (MRE) by tomoelastography, and diffusion-weighted
      imaging (DWI) for detecting nephropathy in patients with lupus nephritis (LN).
      METHODS: Forty-one subjects (25 patients with LN and 16 age- and sex-matched
      healthy volunteers; LN: mean age, 47.3 +/- 14.8 years; 22 female subjects;
      volunteers: mean age, 43.9 +/- 11.6 years; 13 female subjects) were prospectively
      enrolled. The LN group was further divided into subgroups with normal (LN-nRF,
      GFR > 90 mL/min per 1.73 m) and compromised renal function (LN-cRF, GFR < 90
      mL/min per 1.73 m). All subjects were examined by multifrequency MRE, BOLD
      imaging, and DWI, yielding shear wave speed (SWS; in meter per second), T2*
      relaxation times (in millisecond), and apparent diffusion coefficient (ADC; in
      millimeter square per second), respectively. Renal subregional analysis was
      performed for the medulla (ME), inner cortex (CoI), and outer cortex (CoO).
      Imaging markers were correlated to clinical parameters such as GFR and protein-to
      urine creatinine ratio. Cutoffs and area under the receiver operating curve
      (AUROC) were computed to test diagnostic performances. RESULTS: Compared with CoI
      and CoO, LN-nRF predominantly affects ME tissue (SWS: -7%, P < 0.01; T2*: +9%, P
      < 0.05; ADC: -5%, P = 0.27). Detection of LN-nRF was better with MRE compared
      with BOLD imaging and DWI (AUROC = 0.81, 0.76, not significant), whereas pairing
      MRE with T2* further increased diagnostic power (AUROC = 0.91). Disease
      progression was associated with reduction of SWS also in CoI (LN-nRF, 3.04 +/-
      0.38 m/s; LN-cRF, 2.60 +/- 0.26 m/s; p = 0.013), allowing distinction of LN-nRF
      from LN-cRF (AUROC = 0.83). Diffusion-weighted imaging was only sensitive to LN
      cRF in ME tissue (ADC, -12%; P < 0.05). CONCLUSIONS: Lupus nephritis with normal
      renal function first arises in MRE and BOLD images within ME tissue, progressing
      to CoI tissue once renal function becomes impaired and diffusion of tissue water
      changes.

PMID- 30222648
TI  - In Response.

PMID- 30222649
TI  - Temporal Changes in Ventilator Settings in Patients With Uninjured Lungs: A
      Systematic Review.
AB  - In patients with uninjured lungs, increasing evidence indicates that tidal volume
      (VT) reduction improves outcomes in the intensive care unit (ICU) and in the
      operating room (OR). However, the degree to which this evidence has translated to
      clinical changes in ventilator settings for patients with uninjured lungs is
      unknown. To clarify whether ventilator settings have changed, we searched
      MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for
      publications on invasive ventilation in ICUs or ORs, excluding those on patients
      <18 years of age or those with >25% of patients with acute respiratory distress
      syndrome (ARDS). Our primary end point was temporal change in VT over time.
      Secondary end points were changes in maximum airway pressure, mean airway
      pressure, positive end-expiratory pressure, inspiratory oxygen fraction,
      development of ARDS (ICU studies only), and postoperative pulmonary complications
      (OR studies only) determined using correlation analysis and linear regression. We
      identified 96 ICU and 96 OR studies comprising 130,316 patients from 1975 to 2014
      and observed that in the ICU, VT size decreased annually by 0.16 mL/kg (-0.19 to 
      0.12 mL/kg) (P < .001), while positive end-expiratory pressure increased by an
      average of 0.1 mbar/y (0.02-0.17 mbar/y) (P = .017). In the OR, VT size decreased
      by 0.09 mL/kg per year (-0.14 to -0.04 mL/kg per year) (P < .001). The change in
      VTs leveled off in 1995. Other intraoperative ventilator settings did not change
      in the study period. Incidences of ARDS (ICU studies) and postoperative pulmonary
      complications (OR studies) also did not change over time. We found that, during a
      39-year period, from 1975 to 2014, VTs in clinical studies on mechanical
      ventilation have decreased significantly in the ICU and in the OR.

PMID- 30222650
TI  - Teaching Medical Students Clinical Anesthesia: A View From the United Kingdom.

PMID- 30222651
TI  - Anesthetics and Trauma: A Complex Interaction.

PMID- 30222652
TI  - Vertical and Horizontal Pathways: Intersection and Integration of Enhanced
      Recovery After Surgery and the Perioperative Surgical Home.

PMID- 30222653
TI  - Surveying the Literature: Synopsis of Recent Key Publications.

PMID- 30222654
TI  - In Response.

PMID- 30222656
TI  - Ocular cicatricial pemphigoid.
AB  - PURPOSE OF REVIEW: This review offers recommendations for monitoring disease
      status in ocular cicatricial pemphigoid as well therapeutic options including
      local and systemic therapies. RECENT FINDINGS: A negative biopsy on direct
      immunofluorescence does not preclude a diagnosis of OCP. If a patient's
      cicatrization is active and/or progressive, systemic immunosuppression should be
      commenced. SUMMARY: OCP is a chronic systemic autoimmune disease that requires
      systemic immunosuppression.

PMID- 30222657
TI  - Ocular involvement in atopic disease: a review.
AB  - PURPOSE OF REVIEW: To provide a review of the potential sight-threatening
      sequelae associated with ocular involvement of atopic disease and to discuss the
      management of this chronic condition. RECENT FINDINGS: There has been a
      recognition that atopic keratoconjunctivitis (AKC) is a chronic, inflammatory and
      potentially blinding disease. Recent efforts have focused on steroid sparing,
      systemic T cell and calcineurin inhibitor medications for the treatment of severe
      disease. SUMMARY: Ocular involvement in atopic disease can have a variety of
      clinical manifestations. Progressive disease can be vision threatening,
      especially in younger patients. Prompt and effective treatment through a
      multidisciplinary approach, including ophthalmology, allergy and immunology and
      dermatology, can permit stability of the disease.

PMID- 30222655
TI  - Perioperative Outcomes and Surgical Case Volume in Pediatric Complex Cranial
      Vault Reconstruction: A Multicenter Observational Study From the Pediatric
      Craniofacial Collaborative Group.
AB  - BACKGROUND: Complex cranial vault reconstruction (CCVR) performed to treat
      craniosynostosis can be associated with significant blood loss, transfusion, and
      perioperative complications. The aim of this study was to examine the effect of
      CCVR surgical case volume on perioperative outcomes. We hypothesized that
      surgical case volume is not associated with differences in perioperative
      outcomes. The study primary outcome was total perioperative blood donor
      exposures. Secondary outcomes included the total perioperative transfusion
      volume, major complications, and intensive care unit and hospital length of stay.
      METHODS: The multicenter Pediatric Surgery Perioperative Registry was queried for
      infants and children undergoing CCVR between June 2012 and September 2016.
      Institutions were categorized into low, middle, or high surgical case volume
      groups based on tertiles of the average number of cases performed per month.
      Primary and secondary outcomes were analyzed with respect to these groupings.
      RESULTS: The query yielded 1814 CCVR cases from 33 institutions. Demographics
      were similar among the 3 study groups. An inverse relationship between surgical
      case volume and total perioperative blood donor exposures was observed (P <
      .001). The low-volume group had higher perioperative transfusion volumes (P = .02
      versus middle; P = .01 versus high). There was no significant relationship
      between surgical case volume and the incidence of major postoperative
      complications or hospital length of stay. CONCLUSIONS: In this study, low
      surgical case volumes were associated with increased total blood donor exposures
      and increased perioperative transfusion volumes. Hospital length of stay was
      homogeneous in the 3 groups, suggesting a limited overall clinical impact of the
      observed transfusion outcome differences.

PMID- 30222658
TI  - Drug-induced uveitis.
AB  - PURPOSE OF REVIEW: Nearly one-half of all uveitis cases seen at tertiary referral
      centers have no identifiable cause. Many systemic, paraocular, intraocular,
      topical medications, and even vaccines can induce intraocular inflammation,
      scleritis, and rarely orbititis and are often overlooked as causes of uveitis.
      This review was undertaken to elucidate the strength of association of these
      medications with uveitis and to make clinicians aware of these associations,
      especially among newer medications. RECENT FINDINGS: Medication-induced uveitis
      has become particularly important and more frequently seen because of the advent
      of biologic therapies such as immune checkpoint inhibitors (ICPIs), BRAF, and MEK
      inhibitors, antivascular endothelial growth factor agents, and antitumor necrosis
      factor agents, as well as newer systemic bisphosphonates are strongly associated
      with uveitis. SUMMARY: The ever-broadening scope of pharmaceuticals now available
      to treat previously untreatable conditions, such as advanced metastatic cutaneous
      melanoma, have resulted in unintended ocular inflammatory diseases.
      Ophthalmologists must recognize that drugs such as ICPIs, BRAF, and MEK
      inhibitors, anti-vascular endothelial growth factor agents, tumor necrosis factor
      alpha inhibitors, cidofovir, bisphosphonates, topical prostaglandin analogues,
      topical brimonidine, BCG vaccination can cause of uveitis. Utilizing a thorough
      review of systems, physicians may readily identify medications that may cause
      uveitis and avoid expensive and unnecessary laboratory testing.

PMID- 30222659
TI  - Identifying Clusters of Recent and Rapid HIV Transmission Through Analysis of
      Molecular Surveillance Data.
AB  - BACKGROUND: Detecting recent and rapid spread of HIV can help prioritize
      prevention and early treatment for those at highest risk of transmission. HIV
      genetic sequence data can identify transmission clusters, but previous approaches
      have not distinguished clusters of recent, rapid transmission. We assessed an
      analytic approach to identify such clusters in the United States. METHODS: We
      analyzed 156,553 partial HIV-1 polymerase sequences reported to the National HIV
      Surveillance System and inferred transmission clusters using 2 genetic distance
      thresholds (0.5% and 1.5%) and 2 periods for diagnoses (all years and 2013-2015,
      ie, recent diagnoses). For rapidly growing clusters (with >=5 diagnoses during
      2015), molecular clock phylogenetic analysis estimated the time to most recent
      common ancestor for all divergence events within the cluster. Cluster
      transmission rates were estimated using these phylogenies. RESULTS: A distance
      threshold of 1.5% identified 103 rapidly growing clusters using all diagnoses and
      73 using recent diagnoses; at 0.5%, 15 clusters were identified using all
      diagnoses and 13 using recent diagnoses. Molecular clock analysis estimated that
      the 13 clusters identified at 0.5% using recent diagnoses had been diversifying
      for a median of 4.7 years, compared with 6.5-13.2 years using other approaches.
      The 13 clusters at 0.5% had a transmission rate of 33/100 person-years, compared
      with previous national estimates of 4/100 person-years. CONCLUSIONS: Our approach
      identified clusters with transmission rates 8 times those of previous national
      estimates. This method can identify groups involved in rapid transmission and
      help programs effectively direct and prioritize limited public health resources.

PMID- 30222660
TI  - Predictors of Mortality Among Hospitalized Patients With Lower Respiratory Tract
      Infections in a High HIV Burden Setting.
AB  - INTRODUCTION: Lower respiratory tract infections (LRTIs) are a leading cause of
      mortality in sub-Saharan Africa. Triaging identifies patients at high risk of
      death, but laboratory tests proposed for use in severity-of-illness scores are
      not readily available, limiting their clinical use. Our objective was to
      determine whether baseline characteristics in hospitalized participants with LRTI
      predicted increased risk of death. METHODS: This was a secondary analysis from
      the Mulago Inpatient Non-invasive Diagnosis-International HIV-associated
      Opportunistic Pneumonias (MIND-IHOP) cohort of adults hospitalized with LRTI who
      underwent standardized investigations and treatment. The primary outcome was all
      cause mortality at 2 months. Predictors of mortality were determined using
      multiple logistic regression. RESULTS: Of 1887 hospitalized participants with
      LRTI, 372 (19.7%) died. The median participant age was 34.3 years (interquartile
      range, 28.0-43.3 years), 978 (51.8%) were men, and 1192 (63.2%) were HIV-positive
      with median CD4 counts of 81 cells/uL (interquartile range, 21-226 cells/uL).
      Seven hundred eleven (37.7%) participants had a microbiologically confirmed
      diagnosis. Temperature <35.5 degrees C [adjusted odds ratio (aOR) = 1.77, 95%
      confidence intervals (CI): 1.20 to 2.60; P = 0.004], heart rate >120/min (aOR =
      1.82, 95% CI: 1.37 to 2.43; P < 0.0001), oxygen saturation <90% (aOR = 2.74, 95%
      CI: 1.97 to 3.81; P < 0.0001), being bed-bound (aOR = 1.88, 95% CI: 1.47 to 2.41;
      P < 0.0001), and being HIV-positive (aOR = 1.49, 95% CI: 1.14 to 1.94; P = 0.003)
      were independently associated with mortality at 2 months. CONCLUSIONS: Having
      temperature <35.5 degrees C, heart rate >120/min, hypoxia, being HIV-positive,
      and bed-bound independently predicts mortality in participants hospitalized with
      LRTI. These readily available characteristics could be used to triage patients
      with LRTI in low-income settings. Providing adequate oxygen, adequate intravenous
      fluids, and early antiretroviral therapy (in people living with HIV/AIDS) may be
      life-saving in hospitalized patients with LRTI.

PMID- 30222661
TI  - Identification of a Syndemic of Blood-Borne Disease Transmission and Injection
      Drug Use Initiation at the US-Mexico Border.
AB  - BACKGROUND: Efforts to prevent injection drug use (IDU) are increasingly focused
      on the role that people who inject drugs (PWID) play in the assistance with
      injection initiation. We studied the association between recent (ie, past 6
      months) injection-related HIV risk behaviors and injection initiation assistance
      into IDU among PWID in the US-Mexico border region. SETTING: Preventing Injecting
      by Modifying Existing Responses (PRIMER) is a multicohort study assessing social
      and structural factors related to injection initiation assistance. This analysis
      included data collected since 2014 from 2 participating cohorts in San Diego and
      Tijuana. METHODS: Participants were 18 years and older and reported IDU within
      the month before study enrollment. Logistic regression analyses were conducted to
      assess the association between recent injection-related HIV risk behaviors (eg,
      distributive/receptive syringe sharing, dividing drugs in a syringe, and
      paraphernalia sharing) and recent injection initiation assistance. RESULTS: Among
      892 participants, 41 (4.6%) reported recently providing injection initiation
      assistance. In multivariable analysis adjusting for potential confounders,
      reporting a higher number of injection-related risk behaviors was associated with
      an increased odds of recently assisting others with injection initiation
      (adjusted odds ratio per risk behavior: 1.3; 95% confidence interval: 1.0 to 1.6,
      P = 0.04). CONCLUSIONS: PWID who recently engaged in one or more injection
      related HIV risk behavior were more likely to assist others in injection
      initiation. These results stress the syndemic of injection initiation and risk
      behaviors, which indicates that prevention of injection-related HIV risk
      behaviors might also reduce the incidence of injection initiation.

PMID- 30222662
TI  - Radial and femoral access for interventional fellows performing diagnostic
      coronary angiographies: the LEARN-Cardiogroup II, a prospective multicenter
      study.
AB  - BACKGROUND: Safety and efficacy of radial and femoral access for coronary
      angiography performed by cardiology fellows remain to be evaluated. METHODS: In
      this multicenter prospective study, cardiology fellows selected the access site
      (among femoral, right and left radial artery) for coronary angiography. All
      bleeding events related to the access site and all complications (a composite of
      all bleedings and artery occlusion) were the co-primary safety end points.
      Success for each access site, procedural and radiological times and single
      components of primary outcome were the secondary ones. RESULTS: Overall, 201
      patients were enrolled. Fellows chose right radial, left radial or femoral access
      in 164 (82%), 20 (10%) and 17 (8%) cases, respectively. All-cause bleedings were
      lower in radial cohort (4 vs. 19%; P = 0.001) mainly driven by minor bleedings (4
      vs. 18%, P = 0.012). Also, overall complications were less frequent with the
      radial approach (18 vs. 30%, P = 0.03) and radial artery occlusion did not differ
      between right vs. left side (4 vs. 5%, P = 0.76). Procedural time (minutes) was
      similar between radial and femoral site (23 +/- 9 vs. 22 +/- 10, P = 0.91), as
      well as time of X-ray exposure (6 +/- 3 vs. 4 +/- 2, P = 0.11), DAP (Gy/cm: 17 +/
      11 vs. 18 +/- 12, P = 0.74) and amount of contrast medium (ml: 106 +/- 81 vs. 84
      +/- 43, P = 0.89). Success for access was significantly higher with radial artery
      (89 vs. 71%, P = 0.004). CONCLUSION: Radial artery is the most exploited access
      by cardiologist fellows, leading to reduction in minor bleedings and higher
      success compared with femoral access. No differences in procedural time and
      radiation exposures were recorded.

PMID- 30222663
TI  - Iron deficiency in heart failure.
AB  - : Due to aging of the patients with heart failure, comorbidities are an emerging
      problem and, among them, iron deficiency is an important therapeutic target,
      independently of concomitant hemoglobin level. Iron deficiency affects up to 50%
      of heart failure patients, and it has been largely established its association
      with poor quality of life, impaired exercise tolerance and higher mortality.
      Randomized controlled trials (RCTs) and meta-analyses have demonstrated that
      intravenous iron supplementation in heart failure patients with iron deficiency
      positively affects symptoms, quality of life, exercise tolerance (as measured by
      VO2 peak and 6MWT), with a global trend to reduction of hospitalization rates.
      Current European Society of Cardiology Guidelines for heart failure recommend a
      diagnostic work-up for iron deficiency in all heart failure patients and
      intravenous iron supplementation with ferric carboxymaltose for symptomatic
      patients with iron deficiency, defined by ferritin level less than 100 MUg/l or
      by ferritin 100-300 MUg/l with TSAT less than 20%. On-going studies will provide
      new evidence for a better treatment of this important comorbidity of heart
      failure patients.

PMID- 30222664
TI  - Subcutaneous implantable cardioverter defibrillator in cardiomyopathies and
      channelopathies.
AB  - : Cardiomyopathies and channelopathies are heterogeneous disorders that increase
      the risk of sudden cardiac death (SCD). Implantable cardioverter-defibrillator
      (ICD) therapy is safe and effective for preventing SCD in patients at risk for
      malignant ventricular arrhythmias. Because of the poor positive predictive value
      of current risk stratification tools, the majority of patients implanted with an
      ICD will never receive a life-saving therapy but will be exposed to the risk of
      complications such as device infection, lead failure and inappropriate therapy.
      Subcutaneous ICD (S-ICD) now constitutes a valuable alternative to conventional
      transvenous ICD in patients with cardiomyopathies and channelopathies as it
      provides protection from SCD while avoiding the risks of intravascular lead
      infection or failure. This may be particularly advantageous for young patients
      with a very long life expectancy. On the other hand, S-ICD cannot deliver
      antitachycardia pacing or antibradycardia pacing. The purpose of this article is
      to review the available evidence and the future perspectives of S-ICD therapy in
      patients with cardiomyopathies or channelopathies.

PMID- 30222665
TI  - The functional effect of atorvastatin dose-dependent via inflammation factors on
      acute ST segment elevation myocardial infarction after emergency percutaneous
      coronary intervention.
AB  - OBJECTIVE: To investigate the effect of different doses of atorvastatin on
      patients with acute ST segment elevation myocardial infarction (MI) after
      emergency percutaneous coronary intervention (PCI). METHODS: A total of 265
      patients with acute ST segment elevation MI who underwent emergency PCI were
      enrolled, 133 in high-dose atorvastatin administration (40 mg/day) and 132 in
      moderate-dose atorvastatin administration (20 mg/day). All the patients continued
      treatment for 1 year. The incidences of major adverse cardiovascular events
      (MACE) were recorded, including cardiovascular death, spontaneous MI, and
      unplanned revascularization. The association between clinical incidences and
      different doses of atorvastatin treatment was studied. RESULTS: Through tracking
      1 year's treatment, the level of low-density lipoprotein cholesterol was lower in
      high-dose atorvastatin administration than in moderate treatment (1.6 +/- 0.6 vs.
      1.8 +/- 0.6, P = 0.041). MACE significantly decreased in high-dose atorvastatin
      administration than in moderate treatment (9.8 vs. 18.2%, P = 0.03). Spontaneous
      MI was significantly more attenuated in high-dose treatment than in moderate
      treatment (6.8 vs. 12.8%, P = 0.03). Unplanned revascularization robustly
      decreased in patients with high-dose administration than those with moderate-dose
      treatment (5.2 vs. 8.3%, P = 0.03). There was no difference in the rate of
      adverse events between the two groups. CONCLUSION: For patients with acute ST
      segment elevation MI who underwent emergency PCI, high-dose atorvastatin could
      provide better performance than moderate-dose in our long-term tracking.

PMID- 30222666
TI  - Physical activity in premenopausal women with asymptomatic peripheral arterial
      disease.

PMID- 30222668
TI  - "Autologous Gluteal Flaps for Gluteal Augmentation in a Circumferential Lower
      Body Lift: Differences and Refinements".

PMID- 30222667
TI  - Where Do We Look? Assessing Gaze Patterns in Breast Reconstructive Surgery with
      Eye-Tracking Technology.

PMID- 30222669
TI  - Minimally Invasive Laparoscopically Dissected Deep Inferior Epigastric Artery
      Perforator Flap: An Anatomical Feasibility Study and a First Clinical Case.

PMID- 30222670
TI  - Reply: The Comparison of Strattice and SurgiMend in Acellular Dermal Matrix
      Assisted, Implant-Based Immediate Breast Reconstruction.

PMID- 30222671
TI  - Lower Body Lift in the Massive Weight Loss Patient: A New Classification and
      Algorithm for Gluteal Augmentation.

PMID- 30222672
TI  - Totally Extra Peritoneal (TEP) DIEP Flap Harvest Assisted by Robot: A Cadaver
      Study and a First Clinical Case.

PMID- 30222673
TI  - Nipple-Areola Complex Reconstruction.

PMID- 30222674
TI  - Reply: Where Do We Look? Assessing Gaze Patterns in Breast Reconstructive Surgery
      with Eye-Tracking Technology.

PMID- 30222675
TI  - The Comparison of Strattice and SurgiMend in Acellular Dermal Matrix-Assisted,
      Implant-Based Immediate Breast Reconstruction.

PMID- 30222676
TI  - The Addition of Platelet-Rich Plasma to Facial Lipofilling: A Double-Blind,
      Placebo-Controlled, Randomized Trial.

PMID- 30222677
TI  - Bile Collection Detected With BrIDA Scintigraphy in a Patient With Hepatocellular
      Carcinoma.
AB  - A 47-year-old man, with a history of anabolic steroid abuse, developed hepatic
      adenomatosis and multifocal hepatocellular carcinoma. He underwent ultrasound and
      CT follow-up, showing multiple solid and fluid hepatic lesions. Consequently,
      hospitalization was required because of high fever (up to 39 degrees C),
      weakness, and anorexia. An abdominal CT scan revealed an enlargement of one of
      the intrahepatic fluid collections. Biochemical and microbiological analyses of a
      fluid sample showed bilirubin and bile acids as well as Streptococcus cristatus
      and Enterobacter cloacae. Thus, the patient underwent Tc-trimethylbromo
      iminodiacetic acid scintigraphy, demonstrating bile collection in the lesion with
      a flow from a bile duct.

PMID- 30222678
TI  - Bone Sequestration as a Consequence of Esophageal Carcinoma Metastasis Detected
      by 18F-FDG PET/CT.
AB  - A bony sequestrum is a single piece of bone present in an area of osteolysis. It
      is separated from the surrounding bone and is primarily observed in patients with
      bone infection. We present our radiographic findings on F-FDG PET/CT in a case of
      esophageal squamous cell carcinoma with a sequestrum in the skull metastasis.

PMID- 30222679
TI  - PET/CT Imaging for Solitary Primary Bone Lymphoma of Thoracic Vertebra.
AB  - Primary bone lymphoma without classic nodal lesions or advanced disease may be
      mistaken for other osseous diseases, especially when involving a single bone
      site. In this patient, a series of imaging modalities including MRI, bone scan,
      and F-FDG PET/CT revealed only 1 solitary osseous lytic lesion with abnormal
      uptake in the third thoracic vertebra, suggesting a primary skeletal malignancy.
      The subsequent histopathologic examination confirmed the diagnosis of diffuse
      large B-cell lymphoma. After chemotherapy, he achieved an excellent clinical and
      metabolic response.

PMID- 30222680
TI  - Bone Flare to Androgen Deprivation Therapy in Metastatic, Hormone-Sensitive
      Prostate Cancer on 68Ga-Prostate-Specific Membrane Antigen PET/CT.
AB  - A 69-year-old man with newly diagnosed prostate cancer PSA 274 ng/mL, Gleason
      4+3, T-stage 3b) underwent Ga-PSMA PET/CT for staging with follow-up scans 6 and
      13 weeks after androgen deprivation therapy (ADT) initiation. Six weeks after ADT
      initiation, lymph node metastases observed at staging showed metabolic and
      radiological regression, whereas the skeleton showed increased PSMA uptake in
      existing bone metastases and several new PSMA-avid lesions. Skeletal PSMA uptake
      decreased after 13 weeks of ADT, and prostate-specific antigen decreased to 16
      ng/mL. These findings suggest the presence of the flare phenomenon to ADT in bone
      metastases seen on PSMA PET/CT.

PMID- 30222681
TI  - FDG PET/CT Findings in TAFRO Syndrome.
AB  - A 67-year-old woman with prolonged fever, thrombocytopenia, and renal dysfunction
      underwent FDG PET/CT to evaluate underlying causes, including malignancy. PET/CT
      showed FDG uptake in ascites, subcutaneous edema, lymph nodes, spleen, and bone
      marrow. Subsequent bone marrow biopsy revealed myelofibrosis, and laboratory
      testing showed elevated concentrations of interleukin 6 in serum and ascites.
      These findings led to the diagnosis of TAFRO syndrome, a variant of multicentric
      Castleman disease, characterized by thrombocytopenia, anasarca, fever, reticulin
      myelofibrosis, and organomegaly. Because TAFRO syndrome is potentially fatal,
      accurate diagnosis is crucial. Characteristic FDG PET/CT findings facilitate the
      diagnosis of TAFRO syndrome, which is generally challenging.

PMID- 30222682
TI  - A Case of Liver Injury Mimicking Metastasis After Gamma Knife Therapy for Lung
      Cancer: Evaluating by 18F-FDG PET/CT.
AB  - A 52-year-old man presented a mixed low-density lesion with high FDG uptake in
      hepatic segment VIII after gamma knife therapy for lung cancer, which was easily
      misdiagnosed as hepatic metastasis. Follow-up PET/CT assessment demonstrated that
      the hepatic lesion was barely observed and without FDG accumulation 5 months
      after radiotherapy. This case suggests that a new FDG-avid lesion at PET/CT after
      radiotherapy for lung cancer can be caused by radiation-induced liver injury.
      Knowledge of its imaging characteristics and nature course evaluated by follow-up
      PET/CT is critical to avoid misinterpretation of this lesion as metastases.

PMID- 30222683
TI  - Huge Abdominal Photopenic Area Due to Kidney Cyst Imaged by Bone Scintigraphy in
      a Prostate Cancer Patient.
AB  - Bone scintigraphy is a method of choice in evaluating metastatic disease in
      patients with prostatic cancer. We describe the case of a 77-year-old man who was
      subjected to bone scan for evaluation of secondary metastatic disease due to an
      elevated prostatic-specific antigen level (7.2). Bone scintigraphy demonstrated a
      huge photopenic area in the left upper abdominal area, as a result of a huge
      kidney cyst (15 * 13 cm).

PMID- 30222685
TI  - The Relation Between Morphometric Features and Susceptibility to Mandibular Angle
      Fractures.
AB  - The study was aimed to determine possible relations between skeletal morphologic
      parameters to mandibular angle fractures. Retrospective study of 100 patients
      suffering from mandibular fractures and treated in the Rambam Health Care Campus
      between the years 2013 and 2017 was conducted. Predictor variable was facial
      skeletal morphologic features as derived from the measurements. Outcome variable
      was mandibular angle fractures. About 42 patients suffered from angle fractures.
      Gonial angle (131.3 degrees  versus 118.1 degrees ), condylar neck width (8.3 mm
      versus 6.8 mm sagittaly and 7.1 mm versus 5.8 mm horizontally), and wisdom tooth
      prevalence and impaction were positively correlated to the fracture. Ramus height
      (48.3 mm versus 53.4 mm) was negatively correlated to angle fractures. Many
      reports in the literature show positive relations between impacted 3rd molars and
      angle fractures, yet only sporadic reports describe relations between facial
      fractures and facial features. Our results showed the predictable positive
      relation between angle fractures and 3rd molar prevalence and impaction. Yet
      surprisingly, we found unequivocal significant positive correlation between angle
      fractures to gonial angle and condylar neck width and negative correlation to
      ramus height. Based on the correlation to the gonial angle and ramal height, it
      is concluded that enlarged anterior vertical growth is a predictor for angle
      fractures, as are condylar neck width, and wisdom teeth.

PMID- 30222684
TI  - Incidental Orbital Neuroendocrine Metastases on 111In-OctreoScan and MRI.
AB  - Neuroendocrine tumors have a propensity to metastasize, but rarely to the orbits.
      A 69-year-old woman with history of neuroendocrine tumor of pancreatic primary
      underwent routine follow-up In-pentetreotide (OctreoScan) imaging, with 24-hour
      whole-body planar images showing subtle right periorbital tracer uptake that
      localized to extraocular muscles on subsequent SPECT/CT. Orbital MRI further
      defined the location of these highly suspicious orbital metastases, which were
      treated with external radiation, with follow-up MRI showing decreased size of the
      orbital metastases. Early identification and treatment of orbital metastases is
      critical to help preserve vision and quality of life.

PMID- 30222686
TI  - Morphometric Analysis of the Facial Profile: Contour of the Side Face and its
      Variations.
AB  - Much research has been conducted on the morphological characteristics of the
      Chinese. However, very few facial measurements have been documented, especially
      of the side face. This study uses geometirc morphometric method to analyze the
      contour and variations of the side face in Bai and Yi ethnic minorities from
      Yunnan province, China. The mark collection proves that for the Bai ethnicity,
      the variations of the nose are comparatively large, while the forehead variations
      are small. Variations around the lips and the chin are the largest. For the Yi
      ethnicity, the forehead also witnesses small variations and the nose again has
      large variations. The area around the glabella has large variations. Through the
      comparisons, the area around the glabella tends to extrude more in males both in
      Bai and Yi. The situation, however, is much more different when it comes to the
      trichion landmark collection where we see an apparent intrusion in males. For the
      trichion, Yi people are more intruded than the Bai. Similarities between Bai and
      Yi are demonstrated by principal component analysis: one can roughly set the
      males apart from the females using the vertical axis. Profile at the end of
      horizontal axis suggests that the female facial profile has the following
      features: the nose is not so prominent as the male, the forehead and the nose are
      linked by an noticeable arc, the forehead is comparatively steep and is almost in
      a vertical plane with the lips and the chin. By comparison, the male has a
      flatter forehead, a more prominent nose, an obvious sellion, and an intruded
      chin. The common morphologic features of the Chinese face may be reflected
      through these similarities.

PMID- 30222688
TI  - Thigh and Psoas Major Muscularity and Its Relation to Running Mechanics in
      Sprinters.
AB  - PURPOSE: We aimed to examine the morphological characteristics of the thigh and
      psoas major muscles in sprinters as well as interrelations among their
      muscularity, hip joint mechanics, and running speed during maximal running.
      METHODS: T1-weighted magnetic resonance images of the thigh and trunk were
      obtained from 15 male sprinters (best 100-m sprint times, 10.63-11.57 s) and 12
      untrained men. From the magnetic resonance images, the volumes of each of the
      quadriceps femoris and hamstrings, total adductors, sartorius, tensor fasciae
      latae, gracilis, and psoas major were determined. For sprinters, the kinetic and
      kinematic data were measured using a three-dimensional motion capture system and
      force plates during maximal running. The data for one step from the foot strike
      of the stance leg to that of the swing leg were analyzed. The center of gravity
      (CG) velocity and hip joint kinetics were quantified. RESULTS: Compared with
      untrained men, sprinters had significantly greater thigh muscle volumes of the
      hip flexors and extensors, total adductors, gracilis, and psoas major, whereas
      the monoarticular knee extensor and flexor thigh muscle volumes were similar
      between the two groups. The CG velocity was positively correlated with the hip
      flexion angular impulse. Only the rectus femoris volume was significantly
      correlated with the CG velocity and peak hip flexion moment for the swing leg (r
      = 0.66-0.69). CONCLUSIONS: The sprinters in this study presented greater
      muscularity of the thigh and psoas major but not the monoarticular knee extensor
      or flexor muscles. The rectus femoris, in particular, may play an important role
      during the swing phase of sprinting.

PMID- 30222687
TI  - Moderate Exercise Enhances Endothelial Progenitor Cell Exosomes Release and
      Function.
AB  - PURPOSE: Exercise has cardiovascular benefits which might be related to
      endothelial progenitor cells (EPC). Meanwhile, there is evidence suggesting that
      EPC-derived exosomes (EPC-EX) promote vascular repair and angiogenesis through
      their carried microRNA (miR)-126. In this study, we investigated whether exercise
      could increase the levels of circulating EPC-EX and their miR-126 cargo, and by
      which promote the protective function of EPC-EX on endothelial cells (EC).
      METHODS: Plasma EPC-EX from sedentary, low, or moderate exercise mice,
      respectively, denoted as EPC-EX, EPC-EX, and EPC-EX, were isolated using
      microbead-based sorting techniques and characterized by nanoparticle tracking
      analysis, Western blot, and quantitative real-time polymerase chain reaction
      assessments of biomarkers and miR-126. High glucose (25 mM) with hypoxia (1% O2)
      was used for inducing an EC injury model. The injured EC were treated by
      coculturing with vehicle, EPC-EX, EPC-EX, EPC-EX, or EPC-EX + anti-miR-126. After
      that, EC were used for flow cytometry analysis of apoptosis, assessments of tube
      formation and migration, and measurements of miR-126 level and its downstream
      sprouty-related protein-1 (SPRED1) and vascular endothelial growth factor (VEGF).
      RESULTS: 1) Isolated EPC-EX positively expressed exosomal markers (CD63 and
      Tsg101) and EPC markers (CD34 and VEGFR2). 2) Exercise intensity dependently
      elevated plasma level of EPC, EPC-EX/EPC ratio, and miR-126 expression in EPC and
      EPC-EX. 3) Injured EC displayed apoptosis increment, angiogenic dysfunction and
      miR-126 reduction. 4) EPC-EX had better effects than EPC-EX and EPC-EX on
      alleviating those changes of injured EC, accompanied with SPRED1 downregulation
      and VEGF upregulation. 5) The effects of EPC-EX were abolished by miR-126
      knockdown. CONCLUSIONS: Our data demonstrate that exercise can increase EPC-EX
      release and miR-126 level and enhance the effects of EPC-EX on protecting EC
      against injury through the SPRED1/VEGF pathway.

PMID- 30222689
TI  - Is Daily Composition of Movement Behaviors Related to Blood Pressure in Working
      Adults?
AB  - INTRODUCTION: To investigate the association of the daily composition of time
      spent sedentary, in light physical activity and moderate-to-vigorous physical
      activity and time in bed (movement behaviors) with blood pressure (BP) among
      white- and blue-collar workers. METHODS: Systolic BP (SBP), diastolic BP (DBP)
      and body mass index of 827 workers were objectively measured. Daily composition
      of movement behaviors was derived from an Actigraph placed on the thigh for 1 to
      5 d using the Acti4 software (2012-2013). The composition was expressed as
      isometric log-ratios. The cross-sectional associations between daily movement
      behavior composition and BP were investigated using the Compositional Data
      Analysis approach. The associations were adjusted for age, sex, body mass index,
      lift/carry duration, medication intake, and job sector. RESULTS: Daily
      composition of time spent in movement behaviors was significantly associated with
      SBP (F = 2.84, P = 0.04), but not DBP (F = 0.48, P = 0.69). Specifically, time
      reallocation to sedentary time and light physical activity from the remaining
      behaviors was deleteriously associated with SBP, whereas time reallocation to
      time in bed and moderate-to-vigorous physical activity from the remaining
      behaviors was beneficially associated with SBP. However, the results were only
      significant for time spent sedentary (P = 0.01) and in bed (P = 0.047).
      CONCLUSIONS: Daily composition of movement behaviors is associated with SBP among
      workers. Spending more time sedentary compared with other behaviors was
      deleteriously associated with SBP, whereas spending more time in bed was
      beneficially associated with SBP. How time is spent in different movement
      behaviors throughout the day is important for BP and needs to be further
      investigated to be included in future clinical practice guidelines.

PMID- 30222690
TI  - Clonal heterogeneity of melanoma in a paradigmatic case study: future prospects
      for circulating melanoma cells.
AB  - The management of metastatic melanoma is a difficult matter. Nevertheless, the
      advent of target therapy has significantly improved patient outcome, provided
      that tumor molecular characteristics become available: the detection of drug
      resistant clones can contribute to understanding the reasons for resistance
      onset, influencing the choice of subsequent therapy. This work aimed to provide a
      possible explanation for the early resistance to vemurafenib developed by a
      patient with melanoma, and concurrently to assess the extent, and role, of the
      tumor clonal heterogeneity. We analyzed tissue samples from different sites and
      time points: first/second primary, three lymph node metastases, and circulating
      melanoma cells (CMCs). We first investigated these samples by the routine Sanger
      sequencing for BRAF, NRAS, and KIT, and then, we focused on specific hotspots by
      droplet digital PCR. We detected a BRAF V600E mutation by Sanger sequencing in
      the second primary and distant lymph node metastases, but not in the first
      primary or sentinel lymph node. Interestingly, by droplet digital PCR, the V600E
      mutation was also detected in the first primary, and the V600K in the second
      primary and metastases. Moreover, we identified a rare KIT V569G mutation,
      appearing to be CMC exclusive. This finding confirms the potential of CMCs as a
      source of tumor material for genetic analysis, reflecting real-time systemic
      disease evolution and, most likely, the most aggressive, treatment-resistant
      clones. In summary, this work underlines the importance of CMCs in the early
      identification of tumor clones putatively responsible for therapy resistance.

PMID- 30222691
TI  - "Rule of Spence" and Dickman's Classification of Transverse Atlantal Ligament
      Injury Revisited: Discrepancy of Prediction on Atlantoaxial Stability Based on
      Clinical Outcome of Non-Operative Treatment for Atlas Fractures.
AB  - STUDY DESIGN: a retrospective study. OBJECTIVE: To evaluate the prediction
      accuracy of "Rule of Spence" and Dickman's classification of the transverse
      atlantal ligament (TAL) injury on clinical outcomes (mainly focused on
      atlantoaxial stability) of atlas fractures treated non-operatively. SUMMARY OF
      BACKGROUND DATA: TAL is regarded as primary stabilizer of the atlantoaxial
      complex. Atlas fractures are categorized as unstable and stable according to TAL
      injury or not. "Rule of Spence" and Dickman's classification have been widely
      utilized to evaluate the integrity of TAL indirectly or directly. However, there
      is controversy about how to interpret and apply these image measures
      appropriately in treatment decision-making, and comparing the two measures in
      same cohort has been lack. METHODS: From January, 2013 to December, 2015, 13
      adult patients with atlas fractures, treated non-operatively at acute
      posttraumatic phase and followed up for at least two years, were enrolled in the
      study. Lateral mass offset (LMO) and TAL injury were measured by radiography.
      Atlantoaxial stability, pain in occipital region, limitation of cervical motion,
      neurological dysfunction and quality of daily life were evaluated as clinical
      outcomes. RESULTS: LMO < 6.9 mm was inaccurate either to excluded TAL injury
      (4/8, 50% failed) or to predict clinical outcomes (2/8, 25% failed), while
      LMO>6.9 mm was accurate to determine TAL injury (5/5, 100% succeeded) but not to
      predict atlantoaxial stability (4/5, 80% failed). Two cases with Dickman's
      classification type I injury (100%) failed to restore C1-2 stability and six of
      seven type II (85.7%) succeeded. Three patients were indicated for fusion surgery
      due to instability, and one due to traumatic arthritis. Overall clinical outcomes
      were satisfactory as pain and quality of life were considered. CONCLUSIONS:
      Dickman's classification of TAL injury is of higher superiority to "Rule of
      Spence" in term of the accuracy of predicting atlantoaxial stability of non
      operatively treated atlas fractures. LEVEL OF EVIDENCE: 4.

PMID- 30222692
TI  - A Comparison of the Initial Cost Associated With Resection Versus Laparoscopic
      Radiofrequency Ablation of Small Solitary Colorectal Liver Metastasis.
AB  - INTRODUCTION: The aim of this report was to perform a cost-comparison between
      liver resection (LR) and radiofrequency ablation (RFA). METHOD: Patients with
      colorectal liver metastasis (CRLM)<=3 cm, who underwent LR or laparoscopic RFA
      between 2006 and 2015 were included in the study. Using a prospectively
      maintained CRLM database, clinical, oncologic, and financial parameters were
      compared. RESULTS: Sixty-three patients underwent open or laparoscopic LR, and 25
      patients underwent laparoscopic RFA. No significant difference was noted in
      postoperative complications, readmission rate, and local recurrence rate. With a
      median follow-up of 40 months for RFA, and 36 months for LR (P=0.61), mean cancer
      specific overall survival was 51 months for RFA and 63 months for LR (P=0.64).
      The median disease-free survival was 14 months for RFA, and 21 months for LR
      (P=0.59). The mean operating room and hospital costs were 51% and 55% higher in
      the LR (P<0.001, each). CONCLUSIONS: The results of the study suggest that in
      selected patients with small solitary CRLM, laparoscopic tumor ablation might
      offer opportunities for cost-savings compared with resection as the primary
      treatment. This model may suggest possible equivalent oncologic outcomes between
      the 2 modalities.

PMID- 30222693
TI  - Balloon-occluded Retrograde Transvenous Obliteration of Portovenous Shunts During
      Endoscopic Therapy for the Treatment of Gastric Varices.
AB  - INTRODUCTION: To explore the safety and feasibility of balloon-occluded
      retrograde transvenous obliteration (BRTO) of portovenous shunts during
      endoscopic cyanoacrylate injection for the treatment gastric varices (E-BRTO)
      secondary to portal hypertension. PATIENTS AND METHODS: A total of 28 cirrhotic
      patients with gastroesophageal varices and concurrent gastrorenal or
      gastrosplenorenal shunt, treated with E-BRTO, were enrolled. Operative details
      were recorded to evaluate the safety, feasibility, and efficacy of the procedure.
      Short-term follow-up was conducted to denote any incidence of distant emboli,
      variceal rebleeding, or mortality (Video, Supplemental Digital Content 1,
      http://links.lww.com/SLE/A179). RESULTS: All the patients successfully received E
      BRTO without intraoperative complications. The average volume of cyanoacrylate
      was 2.4+/-1.3 mL. During the 90 days follow-up, none of the patients experienced
      distant systemic emboli. However, 8 patients suffered from gastrointestinal
      rebleeding, including one death, while 2 patients were lost to follow-up. The
      short-term rebleeding rate (intention to treat) was about 36% in E-BRTO for this
      subset of patients. CONCLUSIONS: BRTO during endoscopic cyanoacrylate injection
      is an alternative selection for cirrhotic patients with portovenous shunts. The
      procedure is feasible and procedurally safe, but the associated high rebleeding
      rate may require a multimodality approach.

PMID- 30222694
TI  - The Learning Curve for Surgeons Regarding Endoscopic Thyroidectomy via the Oral
      vestibular Approach.
AB  - BACKGROUND: For selected patients, endoscopic thyroidectomy via the oral
      vestibular approach (ETOVA) can be used to achieve a very good esthetic effect.
      This study aimed to assess the learning curve for ETOVA and identify
      improvements. PATIENTS AND METHODS: This retrospective study evaluated the
      outcomes of 101 patients who underwent ETOVA by surgeons A and B. The patients
      were classified according to whether they had undergone surgery during the
      primary or advanced stage of the learning curve, respectively. Proficiency with
      the procedure in various types of cases and the operation time, operative blood
      loss, hospital stay length, and postoperative complications were analyzed.
      RESULTS: In total, 56 and 45 patients were treated by surgeons A and B,
      respectively. For both surgeons, the operation times decreased considerably after
      20 cases. Statistically significant differences with respect to stage were
      observed in terms of operation time (P<0.05) and drainage tube reservation
      (P<0.05). By contrast, significant differences were not observed between stages
      in terms of operative blood loss (P>0.05) or postoperative hospital stay length
      (P>0.05). The total postoperative complication rate was low and comparable with
      that of open surgery. CONCLUSIONS: The specific learning curve identified for
      ETOVA suggests that surgeons with sufficient endoscopic surgery experience could
      achieve a stable proficiency after ~20 cases. A standardized training program and
      exposure to more cases would reduce the learning curve.

PMID- 30222695
TI  - The Impact of Magnesium Sulfate on Pain Control After Laparoscopic
      Cholecystectomy: A Meta-Analysis of Randomized Controlled Studies.
AB  - INTRODUCTION: Magnesium sulfate has emerged as an important drug to alleviate the
      pain after laparoscopic cholecystectomy. However, the use of magnesium sulfate
      for pain control after laparoscopic cholecystectomy has not been well
      established. We conduct a systematic review and meta-analysis to evaluate the
      impact of magnesium sulfate on pain control after laparoscopic cholecystectomy.
      MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Central Register of
      Controlled Trials are searched. Randomized controlled trials assessing the
      influence of magnesium sulfate treatment versus placebo on pain control after
      laparoscopic cholecystectomy are included. Two investigators have independently
      searched articles, extracted data, and assessed the quality of included studies.
      This meta-analysis is performed using the random-effect model. RESULTS: Four
      randomized controlled trials involving 263 patients are included in the meta
      analysis. Compared with control intervention after laparoscopic cholecystectomy,
      magnesium sulfate can substantially decrease pain scores at 2 hours [standard
      mean differences (MD)=-0.45; 95% confidence interval (CI)=-0.88 to -0.02; P=0.04]
      and 8 hours (standard MD=-0.62; 95% CI=-0.95 to -0.28; P=0.0003), as well as
      reduce analgesic consumption (standard MD=-0.40; 95% CI=-0.73 to -0.07; P=0.02),
      but has no substantial influence on pain scores at 24 hour (standard MD=-0.38;
      95% CI=-0.79 to 0.02; P=0.07) and operation duration (standard MD=-0.09; 95% CI=
      0.34 to 0.15; P=0.45). CONCLUSIONS: Magnesium sulfate is effective to reduce pain
      intensity in early stage and anesthetic consumption after laparoscopic
      cholecystectomy.

PMID- 30222696
TI  - Neuroimaging Profiles and Neurodevelopmental Outcome in Infants With Congenital
      Cytomegalovirus Infection.
AB  - BACKGROUND: The accurate stratification of infants with congenital
      cytomegalovirus (CMV) infection at risk for more severe outcome may help in the
      management of patients. Aim of this study was to investigate the ability of a
      comprehensive neuroimaging investigation in predicting the long-term
      neurodevelopmental outcome in patients with congenital CMV. We analyzed the
      prognostic accuracy of a traditional score and a recently proposed scale applied
      to head ultrasound (HUS), computed tomography (CT) and magnetic resonance imaging
      (MRI). METHODS: All consecutive neonates born from 2002 to 2015 with congenital
      CMV infection were considered eligible for the study. Neuroimaging findings were
      scored according to both scores. RESULTS: One hundred seventy infants were
      included (112 symptomatic patients). One-hundred eighteen infants received both
      HUS, CT and MRI. CT and MRI were normal in all 56 asymptomatic patients, while
      32% of them presented an abnormal HUS. The prevalence of abnormal findings
      differed according to the neuroimaging study. The sensitivity of the new
      neuroimaging score in detecting patients at risk for poor neurologic outcome was
      higher than the traditional one for all neuroimaging examinations. CT and MRI
      showed higher positive predictive value compared with HUS. No neuroimaging
      examination showed a negative predictive value equal to 100%. CONCLUSIONS:
      Although HUS is the safest neuroimaging technique, it performs less well in
      detecting some brain abnormalities that can be associated with a poor
      neurodevelopmental outcome. A comprehensive neuroimaging evaluation is mandatory
      in infants with congenital CMV infection to decide for treatment and make a
      prognostic evaluation.

PMID- 30222697
TI  - Vaccine Impact on Long-term Trends in Invasive Bacterial Disease in New Zealand
      Children.
AB  - BACKGROUND: Vaccines against Haemophilus influenzae type B (Hib), Neisseria
      meningitidis and Streptococcus pneumoniae have been serially introduced into the
      New Zealand national immunization schedule since the 1990s. This study aimed to
      describe long-term trends in the rates of these invasive bacterial infections in
      children from New Zealand and compare these to recent UK data. METHODS: This
      population-based observational study used 2 national datasets that collect data
      about hospital discharges (National Minimum Dataset) and notifiable diseases
      (Epurv). Annual age-specific and age-standardized hospital admission rates and
      notification rates were analyzed for all children <15 years of age. RESULTS:
      Hospital admissions for Hib reduced by 79% during the 2 years after the
      introduction of the Hib vaccine (5.94-1.24/100,000). Meningococcal disease
      notifications fell by 75% over 8 years after the introduction of MeNZB vaccine
      (26.15-2.48/100,000) and have continued to decline. Meningococcal disease rates
      were lower than in the United Kingdom despite the absence of an ongoing
      meningococcal vaccination program in New Zealand (8.16 compared with
      10.37/100,000 for 2007-2011). There rates of notifications and hospital
      admissions for pneumococcal disease were discordant, but both reduced
      substantially after the introduction of pneumococcal conjugate vaccines. Maori
      children had the highest rates of disease and the greatest reduction in rates
      after the introduction of both meningococcal and pneumococcal vaccines.
      CONCLUSIONS: Vaccines have had a substantial impact on the rates of invasive
      bacterial disease in children from New Zealand because of Hib, pneumococcus and
      meningococcus. Reductions in rates of disease have been greatest in Maori
      children, improving longstanding disparities in disease burden.

PMID- 30222698
TI  - Preface.

PMID- 30222699
TI  - Recruitment and Engagement in Preventive Clinical Trials: Interdependencies and
      Mediation.
AB  - This article takes a standpoint based in the human and social sciences to examine
      a decisive time in any research related to HIV-AIDS, ie, when healthy,
      seronegative individuals agree to take part in preventive clinical trials. The
      context of recruitment for such trials has been changing over the past several
      decades: the normalization of the epidemic after a period of sensationalism, the
      change in focus of social communities to other causes, the changes in the disease
      from a therapeutic point of view (new drug treatments and preventive drugs), the
      absence of compensation for participation in trials, the absence of any direct
      health benefits for the participants, and the fear of volunteers or the people in
      their lives of the idea of transforming their healthy body into a
      postexperimental body. Research on the prevention of HIV seems to be dependent on
      the consent of a limited number of people and groups because their reasons for
      taking part in such experiments, which are just as much personal as they are for
      the sake of science, are necessarily very particular. How can healthy individuals
      be recruited for preventive HIV trials? What is the social basis and what kind of
      mediation is involved in a mutual understanding between trial participants and
      investigators? Such questions are answered by the authors in this book, who
      approach the issues from a multidisciplinary and diachronic perspective.

PMID- 30222700
TI  - Interview With Jean-Daniel Lelievre, PU-PH, Head of the Research Clinic of the
      VRI (Vaccine Research Institute).

PMID- 30222701
TI  - Targeting Fallible Men: Communication Strategies and Moral Issues in a Pre
      exposure Prophylaxis Trial.
AB  - Based on the analysis of a French pre-exposure prophylaxis trial (Ipergay), and
      focusing on the communication strategies used to recruit volunteers, this article
      explores the figure who serves to justify the trial and who shapes the way in
      which populations concerned by this prevention tool are targeted. We show that
      this figure is that of the fallible man, a classic in moral philosophy: while
      aware of what is good or right for him, he is unable to put this knowledge into
      practice. The targeting of fallible men makes sense in the context of a
      resurgence of high-risk behaviors objectified in the late 1990s: qualifying gays
      who take risks as fallible individuals create a distance with respect to the
      "barebacker" who risks his life deliberately and has no intention of changing his
      behavior. Recognizing that certain gays are vulnerable to risk also provides
      justification for a preventive strategy that acknowledges the inadequacy of
      behavioral prevention, without giving up on prevention altogether. All in all,
      this analysis shows that the technological and epidemiological realism often
      highlighted in pre-exposure prophylaxis interventions is not without a moral
      dimension, attentive to individuals' contradictions and singularities, doubts and
      uncertainties, and to the risk of stigmatization inherent to the acknowledgement
      of risk-taking.

PMID- 30222702
TI  - Being "False Positive": An "Inconvenience"? Debates and Questions Regarding the
      Notion of Vaccine-Induced Seropositivity (VISP) in the Recruitment of Healthy
      Volunteers for a Preventive Anti-HIV Vaccine Trial.
AB  - This article considers a stage in the clinical trial process seldom documented in
      social sciences: recruitment of healthy volunteers for an HIV preventive vaccine
      trial through a media campaign. It analyzes one of the consequences of
      participating in such a clinical trial: the development of vaccine-induced
      seropositivity (VISP) and how this biomedical notion is mobilized both in
      recruitment procedures' normative discourses and from the volunteers' points of
      view, and its consequences on their decision to participate. The interpretations
      of VISP by volunteers depend on several factors: socialization, itinerary into
      the recruitment procedure, sexuality, etc., and generates diverse feelings such
      as indifference, doubt, or even fear. Fear of VISP represents the principal
      refusal reason for those who interrupted their participating step, just before
      inclusion stage. Addressing VISP phenomenon is important because it represents a
      major challenge for the information and the communication procedures for the next
      anti-HIV prophylactic trials recruitment campaigns.

PMID- 30222703
TI  - Exceptional Risk: Healthy Volunteers' Perceptions of HIV/AIDS Clinical Trials.
AB  - As with all early-stage testing of investigational drugs, clinical trials
      targeting HIV/AIDS can pose unknown risks to research subjects. Unlike sick
      participants seeking a therapeutic benefit, the motivations and barriers for
      healthy volunteers are more complex and understudied. Drawing on interviews and
      clinical trial data from 178 healthy volunteers, we examine how they perceive
      HIV/AIDS studies in the early stages of testing. A subset of healthy volunteers
      see phase I HIV/AIDS studies as particularly risky for reasons ranging from fear
      of catching the disease or having long-lasting and uncomfortable side effects to
      inexplicable fears that they cannot even articulate. Some participants have had
      past negative experiences in such trials that inform these views, but others cite
      information from staff and other participants as influential. Healthy volunteers'
      general fears concerning AIDS also shape their views of participating in phase I
      HIV/AIDS clinical trials.

PMID- 30222704
TI  - Social and Behavioral Consequences of Participation in HIV Preventive Vaccine
      Trials in the ANRS COHVAC Cohort.
AB  - From 1992 to 2007, the ANRS (France Recherche Nord & Sud Sida-HIV Hepatites) set
      up a network of healthy volunteers at low risk of HIV infection and participating
      in preventive HIV vaccine phase I and II trials. The objectives of the ANRS
      COHVAC volunteer cohort include the social consequences of trial participation
      and their sexual behavior over time. For 488 volunteers who received a vaccine
      candidate, 462 selection files were collected, and from 2008 to 2016, 355
      volunteers participated in the prospective cohort, including self-administered
      and face-to-face questionnaires administered annually. The volunteer population
      is relatively old, with social characteristics and engagement in society rather
      high. Most volunteers and people around them well accepted the trials, and
      participation in vaccine trials was not followed by increased risk-taking
      regarding HIV infection years later.

PMID- 30222705
TI  - HIV Vaccine Trials: Ethical, Psychological, and Psychological-Social Aspects
      (1991-1996).
AB  - The authors, who took part in designing and conducting the first phase-1 clinical
      trials of the HIV vaccine between 1991 and 1996, discuss the history of this
      innovative program, in particular, the conditions under which volunteers were
      recruited. They recall its multidisciplinary aspects; the team included, along
      with clinicians who were used to performing such trials, epidemiologists,
      psychiatrists, psychoanalysts, social psychologists, and a philosopher
      specialized in ethics. When forming this team, officials at France's National
      Research Agency on AIDS (ANRS) were careful to identify the volunteers social
      characteristics and pay heed to their subjective motivations for participating,
      given the context, namely a rising incidence of HIV infection and the challenges
      that were undermining confidence in medicine. Important in this context was the
      application of the Huriet-Serusclat Act (1988) with its provisions for protecting
      participants. These clinical trials led to reformulating several ethical
      questions, for instance, the tension between the need of such trials and the
      necessity to not expose volunteers to poorly known risks; the importance of
      precise scientific information for delivering free, informed consent; and the
      possibility for volunteers to take part on the basis of their autonomy and "risk
      choice." The network of volunteers, which operated on this basis for nearly 25
      years, is a rare example of collaboration between basic research in biomedicine,
      medical doctors, psychologists, psychoanalysts, and ethicists.

PMID- 30222706
TI  - Logics of Commitment in Vaccine Trials of the ANRS Cohorts 1992-2001.
AB  - In France, participation in vaccine trials is necessarily a personal act that is
      not intended to be made public. It does not involve any direct act of solidarity
      nor does it require any protest or demanding behavior. On the contrary, it
      requires unconditional compliance with the research protocols. However, it is a
      form of individual commitment, which is part of a range of social motives that
      determine the various forms of voluntary involvement in the fight against AIDS:
      financial donations, voluntary work in associations, political activism, etc. In
      this study, we use the application letters of the people who responded to the
      annual recruitment campaigns launched by the Agence Nationale de Recherche sur le
      Sida et les Hepatites (ANRS) to take part as volunteers in vaccine trials related
      to the fight against HIV. At the end of a selection process, a certain number of
      people were recruited every year between 1991 and 2001 and included in a
      "volunteer network" [The application materials were anonymized by the ANRS before
      they were sent to us. The network is defined as a group of volunteers (based on
      the model of blood and bone marrow donors) who have direct contact with the
      researchers in the form of a partnership and not the classic relationship of
      therapeutic dependence, are aware of the absence of any direct benefit and of the
      risks involved, are informed regularly about changes in research, and have the
      possibility to get to know each other during annual meetings and to share their
      experiences, hopes, and any disappointments. Selection was performed in a general
      manner for the purpose of inclusion in the "network" and not for a particular
      trial. The uniqueness of the network facilitates the distribution of volunteers
      between trials for the varying needs of the protocols while reinforcing a sense
      of integration intended to maintain their motivation.]. In addition to the
      application materials, we add a series of informational interviews with several
      people in charge of recruitment for the decade studied, as well as about a dozen
      biographical interviews with volunteers included in the network [The data were
      made available as part of a research project of the ANRS (2003), transformations
      des logiques de l'engagement dans la lutte contre le sida: motifs, facteurs et
      consequences biographiques de l'engagement dans les essais vaccinaux,
      (Transformations in the basis of commitment in the fight against AIDS: reasons,
      factors, and biographical consequences of engagement in vaccine trials), in which
      Philippe Blanchard and Anne Marijnen collaborated for some of the statistics,
      informational interviews with recruiters, and life histories of a group of
      volunteers. Veronique Dore and Yves Souteyrand, through their efforts, were able
      to remove all obstacles to the collection and processing of information. For
      this, we thank them warmly. This article was taken from a lecture given during a
      study day on June 12, 2015, in cooperation with the Vaccine Research Institute,
      entitled Du recrutement pour a l'engagement dans la recherche: Interactions et
      mediations constitutives des recherches en prevention contre le VIH au Nord
      (Recruitment for engagement in research: interactions and mediations in research
      on the prevention of HIV in Western Countries). It also benefited from the
      comments of participants.]. The research consisted of an exploration of 2
      connected aspects: the rationale behind voluntary engagement (the act of
      submitting an application) and the rationale underlying the recruitment (the work
      involved in the selection process of people by the ANRS). In most studies, the
      determinants of engagement are identified based on an analysis of the attributes
      of the selected volunteers but without showing whether these attributes
      distinguish them from applicants who were not selected. In addition,
      "motivations" for engagement are usually collected a posteriori. In this case,
      the corpus of initial application letters offers the possibility of comparing one
      population of applicants with the people who were eventually included in the
      network and distinguishing those who dropped out or refused to be included.

PMID- 30222707
TI  - Postface: Meaning of the Experiment and Implications of the Experience.
AB  - Discussing specifically on the involvement of social sciences in and on the issue
      of recruitment in HIV vaccine trials, the postface of this special issue
      reasserts the importance of social science engagement in clinical research. Three
      entry themes are underlying the discussion: the relationship between the
      individual and society in consent, the analysis of consent as a transaction, the
      examination of the basis, and the context of trust within trials.

PMID- 30222708
TI  - PharmGKB summary: oxycodone pathway, pharmacokinetics.

PMID- 30222710
TI  - The role of genetic polymorphisms in the thymidylate synthase (TYMS) gene in
      methotrexate-induced oral mucositis in children with acute lymphoblastic
      leukemia.
AB  - OBJECTIVE: Methotrexate (MTX) is an important drug in the treatment of pediatric
      acute lymphoblastic leukemia (ALL). MTX is cytotoxic as it impairs DNA and RNA
      synthesis by inhibiting the enzymes dihydrofolate reductase (DHFR) and
      thymidylate synthase (TYMS). The association between genetic variants within the
      TYMS gene and MTX-induced toxicity has been studied, but results are
      inconsistent. We determined the role of three previously described variants
      within the TYMS gene and MTX-induced oral mucositis in a prospective cohort of
      Dutch children with ALL and performed a meta-analysis of the previous results.
      MATERIALS AND METHODS: We analyzed the presence of a 28-base pair tandem repeat
      (rs34743033; 2R3R), a single nucleotide polymorphism present within the 28-base
      pair repeat on the 3R allele (rs2853542; 3RG>C) and a 6-base pair deletion
      (rs15126436; TTAAAG) within the TYMS gene in germline DNA of 117 pediatric
      patients with ALL. Oral mucositis was defined as grade>=3 according to the
      National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE)
      v.3.0. Data were analyzed for the individual rs34743033 (2R3R) and rs151264360 (6
      bp deletion) polymorphisms, whereas rs2853542 (3RG>C) was combined with
      rs34743033 (2R3R) and analyzed according to predicted expression levels of TYMS:
      low expression (2R/2R, 2R/3RC and 3RC/3RC), median expression (2R/3RG and
      3RC/3RG) and high expression (3RG/3RG). We performed a meta-analysis of the
      current literature on these polymorphisms in relation to oral mucositis using a
      fixed effects model. RESULTS: The 2R2R genotype (rs34743033) was not
      significantly associated with developing MTX-induced oral mucositis compared with
      the 2R3R/3R3R genotypes, which was confirmed in a meta-analysis [odds ratio (OR):
      1.17 (0.62-2.19)]. Patients carrying the low-expression TYMS genotype (2R2R,
      2R3RC, 3RC3RC) had an increased odds of developing MTX-induced oral mucositis
      [OR: 2.42 (0.86-6.80)], which did not reach statistical significance. The 6-bp
      deletion [rs151264360, OR: 0.79 (0.20-3.19)] was not associated with the
      development of MTX-induced oral mucositis. CONCLUSION: The TYMS 6-bp deletion and
      2R3R polymorphism were not associated with MTX-induced oral mucositis. Validation
      studies in prospective cohorts are necessary to assess the possible role of the
      low-expression TYMS genotypes in relation to MTX-induced oral mucositis.

PMID- 30222709
TI  - Functional expression of human arylamine N-acetyltransferase NAT1*10 and NAT1*11
      alleles: a mini review.
AB  - The arylamine N-acetyltransferase (NAT) nomenclature committee assigns functional
      phenotypes for human arylamine N-acetyltransferase 1 (NAT1) alleles in those
      instances in which the committee determined a consensus has been achieved in the
      scientific literature. In the most recent nomenclature update, the committee
      announced that functional phenotypes for NAT1*10 and NAT1*11 alleles were not
      provided owing to a lack of consensus. Phenotypic inconsistencies observed among
      various studies for NAT1*10 and NAT1*11 may be owing to variable allelic
      expression among different tissues, the limitations of the genotyping assays
      (which mostly relied on techniques not involving direct DNA sequencing), the
      differences in recombinant protein expression systems used (bacteria, yeast, and
      mammalian cell lines) and/or the known inherent instability of human NAT1
      protein, which requires very careful handling of native and recombinant cell
      lysates. Three recent studies provide consistent evidence of the mechanistic
      basis underlying the functional phenotype of NAT1*10 and NAT1*11 as 'increased
      activity' alleles. Some NAT1 variants (e.g. NAT1*14, NAT1*17, and NAT1*22) may be
      designated as 'decreased-activity' alleles and other NAT1 variants (e.g. NAT1*15
      and NAT1*19) may be designated as 'no-activity' alleles compared with the NAT1*4
      reference allele. We propose that phenotypic designations as 'rapid' and 'slow'
      acetylator should be discontinued for NAT1 alleles, although these designations
      remain very appropriate for NAT2 alleles.

PMID- 30222711
TI  - Biased Competition Favoring Physical Over Emotional Pain: A Possible Explanation
      for the Link Between Early Adversity and Chronic Pain.
AB  - BACKGROUND: Early adversity predisposes to chronic pain, but a mechanistic
      explanation is lacking. Survivors of early adversity with chronic pain often seem
      impaired in their ability to be aware of, understand, and express distressing
      emotions such as anger and fear in social contexts. In this context, it has been
      proposed that pain may at times serve as a "psychic regulator" by preventing
      awareness of more intolerable emotions. METHOD: This narrative review builds on
      the premise that physical pain and emotional pain are conscious experiences that
      can compete for selective attention. We highlight mechanisms whereby the
      consequences of early adversity may put emotional pain at a competitive
      disadvantage. A case history, supportive research findings, and an evidence-based
      neurobiological model are presented. RESULTS: Arising from abuse or neglect in
      childhood, impairments in the adult capacity to attend to and/or conceptualize
      the emotional meaning of felt distress may be associated with impaired engagement
      of the default network and impaired top-down modulation of affective response
      generation processes. Persistent and poorly conceptualized affective distress may
      be associated with reduced emotion regulation ability, reduced vagal tone,
      increased inflammation, and amplified nociceptive signals. Attention to physical
      pain may be reinforced by the temporary reduction in negative emotions that it
      causes. CONCLUSIONS: These processes jointly promote biased competition favoring
      attention to physical pain and away from one's own emotions. They may constitute
      an unintentional analog of the phenomenon of self-injury in patients with
      borderline personality disorder in whom the intentional infliction of physical
      pain serves to downregulate intense emotional distress. Attending to, expressing,
      and understanding previously unacknowledged psychological distress unrelated to
      pain may facilitate recovery from chronic pain after early adversity. Mechanistic
      studies that can validate this clinically derived neurobiological hypothesis are
      urgently needed.

PMID- 30222712
TI  - Does Same-Day Postoperative Increased Intraocular Pressure Affect Endothelial
      Cell Density After Descemet Membrane Endothelial Keratoplasty?
AB  - PURPOSE: High intraocular pressure (IOP) is common in association with
      intracameral air and gas tamponade after Descemet membrane endothelial
      keratoplasty (DMEK); yet its influence on endothelial cell survival is unknown.
      Our aim was to determine the effect of high IOP measured 2 hours after DMEK on 1
      month endothelial cell density (ECD). The influence of other potentially relevant
      factors was also investigated. METHODS: Retrospective, consecutive series.
      Inclusions: low-to-moderate risk DMEK surgery alone or combined with
      phacoemulsification. EXCLUSIONS: previous penetrating keratoplasty or glaucoma
      surgery; grafts with any of the following in the first month: rebubble,
      rejection, or graft failure. RESULTS: Sixty-two grafts met inclusion with 60
      having IOP recorded at 2 hours. Thirty-eight percent (23/60) had IOP >30 mm Hg
      and 22% (13/60) had IOP >40 mm Hg at 2 hours. All grafts with IOP >30 mm Hg had
      air released and immediate normalization of pressure. One-month ECD (mean +/-
      standard error of mean) was 1872 +/- 58 cells/mm, representing cell loss of 29.8
      +/- 2.0%. Two-hour IOP was highly insignificant against 1-month ECD when tested
      as a continuous variable (P = 0.78). Lower 1-month ECD was statistically
      correlated with lower donor count (P = 0.002) and combined DMEK-phaco surgery (P
      = 0.01) on univariate and multivariate analysis. Insignificant factors (P > 0.05)
      against 1-month ECD included patient age, sex and race, surgical indication
      (Fuchs endothelial dystrophy vs. non-Fuchs endothelial dystrophy), and donor age.
      CONCLUSIONS: Increased IOP at 2 hours is common after DMEK, but does not seem to
      influence early endothelial cell survival. One-month ECD was influenced by donor
      counts and combined cataract surgery.

PMID- 30222713
TI  - Superficial Keratopigmentation: An Alternative Solution for Patients With
      Cosmetically or Functionally Impaired Eyes.
AB  - PURPOSE: To report the use of different superficial keratopigmentation (KTP)
      techniques for restoring or enhancing cosmetic appearance of eyes impaired for
      several reasons. METHODS: This is a retrospective, consecutive, noncomparative
      interventional series of cases, in which 136 cosmetically disabled eyes (due to
      different corneal abnormalities) of 130 patients were included. A total of 222
      procedures of superficial manual KTP and superficial automated KTP were
      performed. The procedures were divided into 2 groups: first and second-stage
      procedures. The patients' cosmetic appearance and satisfaction were evaluated and
      graded as excellent, good, or poor. RESULTS: A total of 222 procedures were
      performed, 57.2% were superficial automated KTP, 22.5% were superficial manual
      KTP, and 20.3% included the combination of superficial KTP with other KTP
      techniques. Six procedures were purely cosmetic, 16 therapeutic functional, and
      200 therapeutic cosmetic. Superficial KTP, as a second-stage procedure, was
      performed in 13 eyes that were previously pigmented by intrastromal techniques.
      Superficial KTP as an initial indication (first-stage procedure) alone or in
      combination with another KTP technique in the same surgery was performed in 123
      eyes, in which 44.7% of them were reoperated once or more. Best-corrected visual
      acuity changed insignificantly, and the intraocular pressure decreased
      significantly in all the studied groups. No intraoperative complications were
      observed, 11.2% of eyes with a follow-up time of more than 3 months developed
      postoperative complications. Most of the patients (98.5%) were satisfied.
      CONCLUSIONS: The modern superficial KTP procedure provides the possibility to
      improve the cosmetic appearance of impaired eyes, as an alternative to
      evisceration, enucleation, prosthetic contact lenses, or keratoplasty.

PMID- 30222714
TI  - Descemetorhexis Without Endothelial Keratoplasty Versus DMEK for Treatment of
      Fuchs Endothelial Corneal Dystrophy.
AB  - PURPOSE: To compare the visual outcomes and associated morbidity of patients with
      Fuchs endothelial corneal dystrophy who were treated with either Descemet
      membrane endothelial keratoplasty (DMEK) or descemetorhexis without endothelial
      keratoplasty (DWEK). METHODS: This is a retrospective comparative cohort study of
      27 eyes with mild to moderate Fuchs dystrophy (with corneal guttae/edema limited
      to the central cornea with relatively clear periphery) that were treated at the
      University of Pittsburgh Medical Center from 2015 to 2017 with either DMEK (n =
      15) or DWEK (n = 12). Descemetorhexis was performed by removing the central 4 mm
      of diseased Descemet membrane at the end of phacoemulsification for cataract
      surgery. Visual acuity was measured using the Snellen chart and then converted to
      logMAR for analysis. RESULTS: Average postoperative pinhole visual acuity was
      20/25 - 1 (logMAR 0.16 +/- 0.09) for DMEK eyes and 20/30 + 1 (logMAR 0.13 +/-
      0.10) for DWEK eyes (P = 0.44). The average time to 20/40 vision for DMEK was 2.2
      +/- 2.8 weeks compared with 7.1 +/- 2.7 weeks for DWEK (P < 0.01). In our DMEK
      group, 8 (53%) patients had adverse events, including increased intraocular
      pressure (n = 7), anterior chamber inflammation (n = 1), and graft nonadherence
      (n = 1), with 1 patient requiring anterior chamber paracentesis (6.7%) and 1
      patient (6.7%) requiring a rebubbling procedure. Our DWEK group had no adverse
      events (P < 0.01). CONCLUSIONS: DWEK effectively treats select patients with mild
      to moderate Fuchs dystrophy with equivalent visual outcomes compared with the
      current standard of care, DMEK. Although the recovery time may be longer, DWEK
      patients had reduced adverse events and need for additional procedures and did
      not require long-term immunosuppression or donor corneal tissue.

PMID- 30222716
TI  - Central Islands and Visual Outcomes of Phototherapeutic Keratectomy Using the
      Photorefractive Keratectomy Mode.
AB  - PURPOSE: To compare the rate of central island (CI) and visual acuity after
      phototherapeutic keratectomy (PTK) with and without the CI program. METHODS: This
      retrospective study comprised 147 eyes of 89 consecutive patients (mean age +/-
      SD, 71.1 +/- 9.6 years) undergoing PTK with and without the anti-CI program
      [photorefractive keratectomy (PRK) mode and PTK mode] using the VISX Star S4
      excimer laser system (Johnson & Johnson Vision, Santa Ana, US) for treatment of
      band keratopathy (BK) or granular corneal dystrophy (GCD). The rate of CI
      formation, defined as a steepening area of 3 D, 1.5 mm in diameter, on each
      corneal videokeratographer (ATLAS 9000; Carl Zeiss Meditec, Jena), and best
      spectacle-corrected visual acuity (BSCVA) were assessed 3 months after PTK.
      RESULTS: We found CI formation in 17 eyes (22%) in the PRK mode group and 45 eyes
      (73%) in the PTK mode group at 3 months postoperatively (P < 0.001, chi test).
      Postoperative logarithm of the minimal angle of resolution BSCVA was 0.10 +/-
      0.14 in the PRK group and 0.15 +/- 0.13 in the PTK group (P = 0.019, Student t
      test). The rate of CI was 13 eyes (33%) with BK and 6 eyes (15%) with GCD in the
      PRK mode group and 25 eyes (83%) with BK and 20 eyes (71%) with GCD in the PTK
      mode group. CONCLUSIONS: The use of the anti-CI program for PTK significantly
      decreases the rate of CI formation and significantly improves BSCVA in post-PTK
      eyes, suggesting its viability for treatment of BK and GCD in clinical setting.

PMID- 30222715
TI  - Clinical Characteristics and Outcomes of Moraxella Keratitis.
AB  - PURPOSE: Changing trends of infective keratitis have been identified worldwide.
      The aim of this study was to define the clinical associations, characteristics,
      and outcomes of patients with culture-proven Moraxella keratitis from a large
      tertiary corneal unit in the United Kingdom. METHODS: Patients with confirmed
      Moraxella isolates presenting between January 2004 and November 2016 were
      analyzed. Patient-related factors were examined, including patient demographics,
      date of presentation, clinical presentation, predisposing factors, best-corrected
      visual acuity (BCVA), treatment plans, and clinical outcomes. RESULTS: Eighty-six
      patients were identified, of whom 61 (70.9%) had at least one recognized
      predisposing factor. The median BCVA at presentation was 2.60 logarithm of the
      minimum angle of resolution (logMAR), which improved to median = 0.60 logMAR at
      final visit (P < 0.001). Visual improvement of more than 2 Snellen lines was
      achieved in 60.7% of eyes. A significant relationship (P = 0.003) between final
      vision and the presence of hypopyon was found, where for a fixed BCVA at
      presentation those with a hypopyon achieved a better final visual acuity of 0.69
      logMAR. CONCLUSIONS: Our study showed that although most patients presented with
      at least one predisposing factor, some of the more traditionally perceived risk
      factors may need to be reconsidered. We have shown that with aggressive
      treatment, favorable visual outcomes can be achieved in most patients.
      Interestingly, the presence of hypopyon at presentation was linked to a better
      visual outcome, likely because such patients had more to gain in visual
      potential.

PMID- 30222717
TI  - Corneal Endothelial Cell Density in Uveal Coloboma Associated With Microcornea.
AB  - PURPOSE: To evaluate the relationship between endothelial cell density (ECD) and
      mean corneal diameter (MCD) in eyes with uveal coloboma associated with
      microcornea. METHODS: Corneal endothelial cell imaging was performed using
      specular microscopy on 22 eyes of 18 subjects diagnosed with uveal coloboma
      associated with microcornea. The MCD was noted as the average of horizontal and
      vertical corneal diameters, which were measured using the ruler tool of the slit
      lamp biomicroscope and Castroviejo calipers. RESULTS: Mean age of the study
      subjects was 29.7 +/- 10.4 years (range, 14-46 years). The MCD was 7.3 +/- 1.1 mm
      (range, 4.9-9 mm). Mean ECD (3436 +/- 316.2 cells/mm) of the study subjects was
      significantly (P < 0.0001) higher than the mean ECD (2761.8 +/- 140.9 cells/mm)
      of age-matched (range, 10-40 years) normal eyes with no ocular pathology. The
      pleomorphism and polymegathism were comparable between the 2 groups. Regression
      analysis showed that MCD had a significant negative (R = -0.55; P = 0.02)
      relationship with ECD. CONCLUSIONS: Eyes with congenital uveal coloboma
      associated with microcornea have increased ECD. Increased ECD may be partly due
      to a reduced posterior corneal surface area in microcornea.

PMID- 30222718
TI  - Corneal Relapse of Peripheral T-Cell Lymphoma Under Systemic Chemotherapy.
AB  - PURPOSE: To report a patient who developed unilateral corneal stromal
      infiltration while undergoing systemic chemotherapy for multinodal peripheral T
      cell lymphoma not otherwise specified. METHODS: Clinical, imaging, and
      immunohistopathological features of a 40-year-old woman who presented with a
      stromal haze in the right cornea were reviewed. RESULTS: At initial presentation,
      her visual acuity in the right eye was 20/40. Slit-lamp examination showed
      stromal infiltration located mainly in the inferotemporal peripheral cornea
      without epithelial or limbal involvement. Immunohistochemical examination of the
      incisional biopsy specimen revealed CD3, CD5, and CD8 neoplastic lymphocytes
      suggestive of T-cell lymphoma. The corneal lesion and disseminated
      lymphadenopathy did not respond to various combinations of several cycles of
      systemic chemotherapy. Remission was achieved only after allogeneic bone marrow
      transplantation. The corneal infiltrates almost totally regressed within 6
      months, and she maintained 20/20 visual acuity thereafter. She did not have any
      systemic or ocular recurrence during 6 years of posttransplantation follow-up.
      CONCLUSIONS: In this rare case of systemic multinodal peripheral T-cell lymphoma,
      corneal stromal infiltration was the only ocular manifestation. Prompt corneal
      biopsy enabled the appropriate diagnosis. Development and persistence of corneal
      infiltration despite systemic chemotherapy may be a warning sign for resistance
      to treatment.

PMID- 30222719
TI  - Post-Laser In Situ Keratomileusis Epithelial Ingrowth: Treatment, Recurrence, and
      Long-Term Results.
AB  - PURPOSE: To study outcomes after surgical removal of epithelial ingrowth (EI) in
      post-laser in situ keratomileusis patients, specifically comparing visual results
      and recurrence rates between 2 different EI management techniques. METHODS: In
      this retrospective chart review of 67 eyes of 54 patients who underwent surgical
      treatment for EI after laser in situ keratomileusis between July 1999 and July
      2014 at the Bascom Palmer Eye Institute, Miami, FL, surgical techniques,
      recurrence rates, visual acuity (VA), and refractive error were assessed.
      RESULTS: Of the 67 eyes, 56 eyes (83.6%) had flap lift + scraping alone, and 11
      eyes (16.4%) had flap lift + scraping + suturing. After mean follow-up of 2.5
      years, 11 of 56 eyes (19.6%) treated with flap lift + scraping alone had EI
      recurrence, whereas no eyes treated with flap lift + scraping + suturing had EI
      recurrence. VA results and refractive errors were better in eyes treated with
      lift + scraping alone compared with lift + scraping + suturing at 1 month. In the
      67 eyes with 1-year follow-up, VA and refractive errors improved from
      preoperative values and were comparable between groups. CONCLUSIONS: Scraping
      alone provides significantly better initial visual outcomes but higher EI
      recurrence rates compared with scrape-suturing. Long-term visual outcomes are
      comparable between 2 techniques.

PMID- 30222720
TI  - Descemet Membrane Endothelial Keratoplasty for Failed Penetrating Keratoplasty:
      Visual Outcomes and Graft Survival.
AB  - PURPOSE: To evaluate outcomes and graft survival of Descemet membrane endothelial
      keratoplasty (DMEK) for failed penetrating keratoplasty (PK). METHODS: Ninety
      three DMEK procedures performed in 84 eyes of 77 patients with failed PK were
      retrospectively reviewed. The main outcomes were corrected distance visual acuity
      and graft survival assessed with Kaplan-Meier survival analysis and proportional
      hazards modeling taking follow-up into consideration. RESULTS: Sixty-nine eyes
      had 1 previous failed PK, 13 had 2, 1 had 3, and 1 had 4. Ten eyes had failed
      Descemet stripping endothelial keratoplasty (DSEK) performed under failed PK.
      Fourteen cases (15%) had previous glaucoma filtration surgery (9 trabeculectomy
      alone; 5 trabeculectomy and aqueous shunt). Median follow-up was 21 months
      (range, 1 month to 7 years). Median Snellen corrected distance visual acuity
      improved from 20/100 preoperatively (range, 20/30 to count fingers) to 20/30 at 6
      months postoperatively (n = 73; range, 20/20-20/200). Rebubbling rates were 53%
      when the diameter of the DMEK graft was oversized, 27% when same sized, and 33%
      when undersized relative to that of the previous PK graft. Two grafts (2%)
      experienced an immunologic rejection episode, and 15 (16%) failed, including 5
      primary/early failures and 10 late failures. Previous glaucoma surgery was the
      only significant risk factor for failure (relative risk, 7.1; 95% confidence
      interval, 2.1-37.0). The 1-, 2-, and 3-year graft survival rates were 96%, 89%,
      and 89% without versus 78%, 53%, and 39% with previous glaucoma surgery.
      CONCLUSIONS: Treatment of failed PK with DMEK produced similar 4-year survival
      (76%) and better visual outcomes than previously reported with Descemet stripping
      endothelial keratoplasty or an initial PK regraft.

PMID- 30222722
TI  - Evaluation of quantitative 123I and 131I SPECT with Monte Carlo-based down
      scatter compensation.
AB  - OBJECTIVE: Quantitative I and I single-photon emission computed tomography
      (SPECT) is hampered by down-scatter from the high-energy peaks. This paper
      presents a down-scatter compensation method, where down-scatter generated in the
      patient and gamma camera collimator and detector is modelled using Monte Carlo
      simulation in the ordered subsets expectation maximization SPECT reconstruction
      algorithm. MATERIALS AND METHODS: The new down-scatter compensation method was
      compared with conventional triple energy window (TEW) scatter compensation and
      Gaussian convolution-based forced detection Monte Carlo methods. The comparison
      was made with the NEMA-IEC phantom using six spherical inserts (diameters from 10
      to 37 mm) and a lung compartment. The phantom was filled with I and I solutions
      to known sphere-to-background concentration ratios. Spherical volumes of interest
      with the same diameter as the inserts were drawn on the images, and recovery
      coefficients for the spheres were calculated in addition to lung-to-background
      ratio. RESULTS: The new down-scatter compensation method provided higher recovery
      coefficients than the TEW scatter compensation or Gaussian convolution-based
      forced detection Monte Carlo algorithm for both isotopes. Background activity
      concentration could be accurately estimated with the new down-scatter
      compensation method and with the TEW scatter compensation, whereas activity
      concentration of the spheres was severely underestimated even with the new
      method. CONCLUSION: Down-scatter compensation with Monte Carlo-simulation
      effectively reduces down-scatter effects in I and I SPECT imaging.

PMID- 30222723
TI  - Effects of thermal stimulation on neurons and astrocytes cultured from the rat
      median preoptic nucleus.
AB  - Warming or cooling of the median preoptic nucleus (MnPO) in-vivo evokes
      appropriate thermoregulatory responses. In the present study, we aimed to
      investigate whether single neurons (and astrocytes) of primary rat MnPO cell
      cultures maintain properties, which are consistent with their putative role
      within the central thermoregulatory structures. Using the fura-2 ratio imaging
      technique, we therefore measured changes of intracellular Ca concentrations
      ([Ca]i) in neurons of rat MnPO primary cultures stimulated by rapid cooling from
      37 to 25 degrees C, or warming from 37 to 45 degrees C, or glutamate, the
      transmitter which transfers thermal information to MnPO neurons. In the first
      experiment, we tested the responses to external cooling in a group of 212
      neurons. Overall, 165 of these neurons were responsive to stimulation with
      glutamate; just four of them responded to the cold-stimulus with an increase of
      [Ca]i, and only one of these neurons was responsive to stimulation with menthol.
      In the second experiment, 24 of 327 neurons and 23 of 241 astrocytes responded to
      external warming with quick and pronounced Ca signals. Another 33 (10%) neurons
      showed a moderate and slowly developing increase of [Ca]i during the warming,
      which reflected the temperature changes in the chamber. These data correspond to
      properties of MnPO neurons upon thermal stimulation obtained by other
      experimental approaches. Primary cultures derived from the rat MnPO can thus be
      used to investigate neuronal thermosensitive properties and their possible
      modulation by other stimuli.

PMID- 30222724
TI  - Posterior cingulate cortex/precuneus blood oxygen-level dependent signal changes
      during the repetition of an attention task in meditators and nonmeditators.
AB  - BACKGROUND AND PURPOSE: Among several cognitive advantages, meditation is thought
      to enhance practitioners' capacity for sustained attention. In the present study,
      we explored this question by testing meditation practitioners (meditators) and
      nonpractitioners (nonmeditators) on a task that requires sustained attention, the
      Stroop Word-Color Task (SWCT), while using functional MRI. PARTICIPANTS AND
      METHODS: Participants were all right-handed and included 23 regular meditators as
      well as 17 nonmeditators. Participants viewed color words (i.e. 'red,' 'blue,' or
      'green') presented one at a time on the screen that were written in either the
      same color (congruent condition) or a different color (incongruent condition) and
      were asked to indicate the color of the print. Participants also viewed noncolor
      words written in unrelated colors (neutral condition). Both groups completed the
      same two acquisition runs. RESULTS: Although both meditators and nonmeditators
      gave faster responses on run 2 than run 1 for both the neutral and incongruent
      trials, nonmeditators showed decreased activation and meditators showed increased
      activation in precuneus/posterior cingulate cortex. These regions were previously
      shown to be activated in the SWCT and belong to default mode network as well as
      to cognitive control network. CONCLUSION: Attention to repetitive stimuli during
      two equal runs of SWCT is mediated by the precuneus/posterior cingulate cortex,
      and mental training through meditation may influence the activity of these
      regions during such tasks.

PMID- 30222725
TI  - Triggering microglia through toll-like receptor 2 pathway induced interferon beta
      expression in cell and animal model of Alzheimer's disease.
AB  - Synaptic function and memory performance are disrupted by soluble form of beta
      amyloid (Abeta). In the previous study, we found that early activation of
      microglia by toll-like receptor 2 (TLR2) attenuated Alzheimer's disease
      associated cognitive deficit. This study was designed to investigate whether
      pretreatment with the TLR2 receptor ligand can regulate microglia to produce
      interferon beta (INFbeta) in a rat model of Alzheimer's disease. For this
      purpose, the BV-2 cell line was cultured in a 24-well plate, treated with Pam3Cys
      (1 MUg/ml), and then incubated with oligomeric Abeta for 24 h. The expression of
      TRIF, IRF3, and INFbeta was measured by western blot technique. For in-vivo
      study, bilateral guide cannulas were streotaxically implanted in the right and
      left lateral ventricles. Pam3Cys/vehicle was microinjected into the right
      ventricle every 3 days. Two weeks later, an osmotic pump was inserted into the
      left ventricle to microinfuse oligomeric Abeta/placebo over 14 days. In the
      meanwhile, treatment with Pam3Cys was continued every 3 days. Then, expression of
      TRIF, IRF3, and INFbeta was measured in the hippocampus. The results showed that
      although oligomeric Abeta could not alter the expression of these proteins at the
      cell and tissue level, treatment with Pam3Cys resulted in enhanced expression of
      them at both cell culture and hippocampal tissue following treatment with
      oligomeric Abeta. It is concluded that stimulation of microglia through TLR2
      pathway induces INFbeta expression, which may in part mediate neuroprotection
      against oligomeric Abeta.

PMID- 30222726
TI  - Does emotion arousal influence the benefit received from testing: insights from
      neural correlates of retrieval mode effect.
AB  - Retrieval can not only assess what was learned in a prior episode but also
      strengthen memory retention. Episodic context account posited that the act of
      thinking back to an original study episode (i.e. being in a retrieval mode) is
      the mechanism of retrieval practice effect. However, whether the retrieval
      practice effect could be influenced by emotional arousal is still unclear. We aim
      to investigate the role of retrieval mode and emotional arousal on retrieval
      practice effect by using event-related potentials. Using negative and neutral
      items, participants were asked to either restudy or perform a source memory test,
      and then a final source memory test was conducted. The behavioral results
      revealed that memory of neutral and negative items similarly benefited from the
      retrieval practice condition. Consistently, event-related potential results
      revealed that retrieval mode effect was found for both the neutral and negative
      items. These findings suggested that emotion arousal might not influence testing
      effect when source memory test was applied for the retrieval practice condition,
      and retrieval mode plays an important role in these effects.

PMID- 30222727
TI  - Extreme Learning Machine (ELM)-Based Classification of Benign and Malignant Cells
      in Breast Cancer.
AB  - BACKGROUND Breast cancer is one of the most common cancer types in the world and
      is a serious threat to health. This type of cancer is complex; it is a hereditary
      disease and does not result from a single cause. The diagnosis of cancer starts
      with a biopsy. Various methods are used to detect and recognize cancer cells,
      from microscopic images and mammography to ultrasonography and magnetic resonance
      images (MRI). MATERIAL AND METHODS Detection and characterization of benign and
      malignant cells by image-processing-based segmentation for breast cancer
      diagnosis is important for early diagnosis. In the present study, Extreme
      Learning Machine (ELM) classification was performed for 9 features based on image
      segmentation in the Breast Cancer Wisconsin (Diagnostic) data set in the UC
      Irvine Machine Learning Repository database. RESULTS The results obtained with
      the developed method were compared with the results of other machine learning
      methods (Naive Bayes, Support Vector Machine, and Artificial Neural Network) and
      it showed the highest performance, with a result of 98.99%. CONCLUSIONS It was
      found that both accuracy and speed were good. We present a method that can be
      applied in cell morphology detection and classification in automated systems that
      classify by computer-aided mammogram image features.

PMID- 30222728
TI  - Emergent mechanics of actomyosin drive punctuated contractions and shape network
      morphology in the cell cortex.
AB  - Filamentous actin (F-actin) and non-muscle myosin II motors drive cell motility
      and cell shape changes that guide large scale tissue movements during embryonic
      morphogenesis. To gain a better understanding of the role of actomyosin in vivo,
      we have developed a two-dimensional (2D) computational model to study emergent
      phenomena of dynamic unbranched actomyosin arrays in the cell cortex. These
      phenomena include actomyosin punctuated contractions, or "actin asters" that form
      within quiescent F-actin networks. Punctuated contractions involve both formation
      of high intensity aster-like structures and disassembly of those same structures.
      Our 2D model allows us to explore the kinematics of filament polarity sorting,
      segregation of motors, and morphology of F-actin arrays that emerge as the model
      structure and biophysical properties are varied. Our model demonstrates the
      complex, emergent feedback between filament reorganization and motor transport
      that generate as well as disassemble actin asters. Since intracellular actomyosin
      dynamics are thought to be controlled by localization of scaffold proteins that
      bind F-actin or their myosin motors we also apply our 2D model to recapitulate in
      vitro studies that have revealed complex patterns of actomyosin that assemble
      from patterning filaments and motor complexes with microcontact printing.
      Although we use a minimal representation of filament, motor, and cross-linker
      biophysics, our model establishes a framework for investigating the role of other
      actin binding proteins, how they might alter actomyosin dynamics, and makes
      predictions that can be tested experimentally within live cells as well as within
      in vitro models.

PMID- 30222729
TI  - Morphology of mitochondria in spatially restricted axons revealed by cryo
      electron tomography.
AB  - Neurons project axons to local and distal sites and can display heterogeneous
      morphologies with limited physical dimensions that may influence the structure of
      large organelles such as mitochondria. Using cryo-electron tomography (cryo-ET),
      we characterized native environments within axons and presynaptic varicosities to
      examine whether spatial restrictions within these compartments influence the
      morphology of mitochondria. Segmented tomographic reconstructions revealed
      distinctive morphological characteristics of mitochondria residing at the
      narrowed boundary between presynaptic varicosities and axons with limited
      physical dimensions (approximately 80 nm), compared to mitochondria in
      nonspatially restricted environments. Furthermore, segmentation of the tomograms
      revealed discrete organizations between the inner and outer membranes, suggesting
      possible independent remodeling of each membrane in mitochondria at spatially
      restricted axonal/varicosity boundaries. Thus, cryo-ET of mitochondria within
      axonal subcompartments reveals that spatial restrictions do not obstruct
      mitochondria from residing within them, but limited available space can influence
      their gross morphology and the organization of the inner and outer membranes.
      These findings offer new perspectives on the influence of physical and spatial
      characteristics of cellular environments on mitochondrial morphology and
      highlight the potential for remarkable structural plasticity of mitochondria to
      adapt to spatial restrictions within axons.

PMID- 30222730
TI  - The topoisomerase 3alpha zinc-finger domain T1 of Arabidopsis thaliana is
      required for targeting the enzyme activity to Holliday junction-like DNA repair
      intermediates.
AB  - Topoisomerase 3alpha, a class I topoisomerase, consists of a TOPRIM domain, an
      active centre and a variable number of zinc-finger domains (ZFDs) at the C
      terminus, in multicellular organisms. Whereas the functions of the TOPRIM domain
      and the active centre are known, the specific role of the ZFDs is still obscure.
      In contrast to mammals where a knockout of TOP3alpha leads to lethality, we found
      that CRISPR/Cas induced mutants in Arabidopsis are viable but show growth
      retardation and meiotic defects, which can be reversed by the expression of the
      complete protein. However, complementation with AtTOP3alpha missing either the
      TOPRIM-domain or carrying a mutation of the catalytic tyrosine of the active
      centre leads to embryo lethality. Surprisingly, this phenotype can be overcome by
      the simultaneous removal of the ZFDs from the protein. In combination with a
      mutation of the nuclease AtMUS81, the TOP3alpha knockout proved to be also embryo
      lethal. Here, expression of TOP3alpha without ZFDs, and in particular without the
      conserved ZFD T1, leads to only a partly complementation in root growth-in
      contrast to the complete protein, that restores root length to mus81-1 mutant
      level. Expressing the E. coli resolvase RusA in this background, which is able to
      process Holliday junction (HJ)-like recombination intermediates, we could rescue
      this root growth defect. Considering all these results, we conclude that the ZFD
      T1 is specifically required for targeting the topoisomerase activity to HJ like
      recombination intermediates to enable their processing. In the case of an
      inactivated enzyme, this leads to cell death due to the masking of these
      intermediates, hindering their resolution by MUS81.

PMID- 30222731
TI  - Destabilized adaptive influenza variants critical for innate immune system escape
      are potentiated by host chaperones.
AB  - The threat of viral pandemics demands a comprehensive understanding of evolution
      at the host-pathogen interface. Here, we show that the accessibility of adaptive
      mutations in influenza nucleoprotein at fever-like temperatures is mediated by
      host chaperones. Particularly noteworthy, we observe that the Pro283
      nucleoprotein variant, which (1) is conserved across human influenza strains, (2)
      confers resistance to the Myxovirus resistance protein A (MxA) restriction
      factor, and (3) critically contributed to adaptation to humans in the 1918
      pandemic influenza strain, is rendered unfit by heat shock factor 1 inhibition
      mediated host chaperone depletion at febrile temperatures. This fitness loss is
      due to biophysical defects that chaperones are unavailable to address when heat
      shock factor 1 is inhibited. Thus, influenza subverts host chaperones to uncouple
      the biophysically deleterious consequences of viral protein variants from the
      benefits of immune escape. In summary, host proteostasis plays a central role in
      shaping influenza adaptation, with implications for the evolution of other
      viruses, for viral host switching, and for antiviral drug development.

PMID- 30222732
TI  - Associations between erythrocyte polymorphisms and risks of uncomplicated and
      severe malaria in Ugandan children: A case control study.
AB  - BACKGROUND: Evidence for association between sickle cell and alpha thalassemia
      trait and severe malaria is compelling. However, for these polymorphisms
      associations with uncomplicated malaria, and for G6PD deficiency associations
      with uncomplicated and severe malaria, findings have been inconsistent. We
      studied samples from a three-arm case-control study with the objective of
      determining associations between common host erythrocyte polymorphisms and both
      uncomplicated and severe malaria, including different severe malaria phenotypes.
      METHOD: We assessed hemoglobin abnormalities, alpha-thalassemia, and G6PD
      deficiency by molecular methods in 325 children with severe malaria age-matched
      to 325 children with uncomplicated malaria and 325 healthy community controls.
      Conditional logistic regression was used to measure associations between
      specified genotypes and malaria outcomes. RESULTS: No tested polymorphisms
      offered significant protection against uncomplicated malaria. alpha-thalassemia
      homozygotes (_alpha/_alpha) had increased risk of uncomplicated malaria (OR 2.40;
      95%CI 1.15, 5.03, p = 0.020). HbAS and alpha-thalassemia heterozygous
      (_alpha/alphaalpha) genotypes protected against severe malaria compared to
      uncomplicated malaria (HbAS OR 0.46; 0.23, 0.95, p = 0.036; _alpha/alphaalpha OR
      0.51; 0.24, 0.77; p = 0.001) or community (HbAS OR 0.23; 0.11, 0.50; p<0.001;
      _alpha/alphaalpha; OR 0.49; 0.32, 0.76; p = 0.002) controls. The alpha
      thalassemia homozygous (_alpha/_alpha) genotype protected against severe malaria
      when compared to uncomplicated malaria controls (OR 0.34; 95%CI 0.156, 0.73, p =
      0.005), but not community controls (OR 1.03; 0.46, 2.27, p = 0.935). Stratifying
      by the severe malaria phenotype, compared to community controls, the protective
      effect of HbAS was limited to children with severe anemia (OR 0.17; 95%CI 0.04,
      0.65; p = 0.009) and that of _alpha/alphaalpha to those with altered
      consciousness (OR 0.24; 0.09, 0.59; p = 0.002). A negative epistatic effect was
      seen between HbAS and _alpha/alphaalpha; protection compared to uncomplicated
      malaria controls was not seen in individuals with both polymorphisms (OR 0.45;
      0.11, 1.84; p = 0.269). G6PD deficiency was not protective against severe
      malaria. CONCLUSION: Associations were complex, with HbAS principally protective
      against severe anemia, _alpha/alphaalpha against altered consciousness, and
      negative epistasis between the two polymorphisms.

PMID- 30222733
TI  - Effects of the particle of ground alfalfa hay on the growth performance, methane
      production and archaeal populations of rabbits.
AB  - The world's annual output of rabbits is over 1.2 billion, therefore this sector
      is also one of the sources of greenhouse gases in livestock production. One
      hundred-twenty New Zealand rabbits were allocated into four treatments, five
      replicates in each treatment and six rabbits in each replicate to examine the
      effect of grinding alfalfa hay to different sizes on growth performance, methane
      production and cecal archaeal populations. The particle sizes of the alfalfa meal
      in the four treatment diets were 2500, 1000, 100 and 10 MUm, while the other
      ingredients were ground through a 2.5 mm sieve. The average daily gain (ADG) and
      average daily feed intake (ADFI) increased (P<0.001) as the particle size
      decreased, but the feed conversion ratio (FCR) was not affected (P = 0.305). The
      digestibility of neutral detergent fiber (NDF) (P = 0.006) and acid detergent
      fiber (ADF) (P<0.006) increased while the greatest digestibility of crude protein
      (CP) was obtained in 1000 um group (P = 0.015). The rabbits produced more methane
      (CH4, L/kgBM0.75/d) with decreasing alfalfa particle size (P<0.001). The molar
      proportion of acetic acid and propionic acid decreased (P<0.001) at the cost of
      butyric acid (P<0.001). The greatest villus height:crypt depth ratio were
      obtained in 1000 MUm group, and the decrease in the alfalfa hay particle size
      decreased the jejunum and ilem villus height:crypt depth ratio (P<0.05). The
      gastric muscular and mucosal thickness decreased with decreasing alfalfa particle
      size (P<0.05). Archaea diversity decreased with decreasing alfalfa particle size,
      and the relative abundance of genus Methanobrevibacter increased (P<0.001) while
      the genus Methanosphaera decreased (P<0.001). It is concluded that a finer
      particle size favors the growth of genus Methanobrevibacter, which produces more
      methane but promotes the growth performance of rabbits.

PMID- 30222734
TI  - EukRef: Phylogenetic curation of ribosomal RNA to enhance understanding of
      eukaryotic diversity and distribution.
AB  - Environmental sequencing has greatly expanded our knowledge of micro-eukaryotic
      diversity and ecology by revealing previously unknown lineages and their
      distribution. However, the value of these data is critically dependent on the
      quality of the reference databases used to assign an identity to environmental
      sequences. Existing databases contain errors and struggle to keep pace with
      rapidly changing eukaryotic taxonomy, the influx of novel diversity, and
      computational challenges related to assembling the high-quality alignments and
      trees needed for accurate characterization of lineage diversity. EukRef
      (eukref.org) is an ongoing community-driven initiative that addresses these
      challenges by bringing together taxonomists with expertise spanning the
      eukaryotic tree of life and microbial ecologists, who use environmental sequence
      data to develop reliable reference databases across the diversity of microbial
      eukaryotes. EukRef organizes and facilitates rigorous mining and annotation of
      sequence data by providing protocols, guidelines, and tools. The EukRef pipeline
      and tools allow users interested in a particular group of microbial eukaryotes to
      retrieve all sequences belonging to that group from International Nucleotide
      Sequence Database Collaboration (INSDC) (GenBank, the European Nucleotide Archive
      [ENA], or the DNA DataBank of Japan [DDBJ]), to place those sequences in a
      phylogenetic tree, and to curate taxonomic and environmental information for the
      group. We provide guidelines to facilitate the process and to standardize
      taxonomic annotations. The final outputs of this process are (1) a reference tree
      and alignment, (2) a reference sequence database, including taxonomic and
      environmental information, and (3) a list of putative chimeras and other
      artifactual sequences. These products will be useful for the broad community as
      they become publicly available (at eukref.org) and are shared with existing
      reference databases.

PMID- 30222735
TI  - Abstract concept learning in a simple neural network inspired by the insect
      brain.
AB  - The capacity to learn abstract concepts such as 'sameness' and 'difference' is
      considered a higher-order cognitive function, typically thought to be dependent
      on top-down neocortical processing. It is therefore surprising that honey bees
      apparantly have this capacity. Here we report a model of the structures of the
      honey bee brain that can learn sameness and difference, as well as a range of
      complex and simple associative learning tasks. Our model is constrained by the
      known connections and properties of the mushroom body, including the
      protocerebral tract, and provides a good fit to the learning rates and
      performances of real bees in all tasks, including learning sameness and
      difference. The model proposes a novel mechanism for learning the abstract
      concepts of 'sameness' and 'difference' that is compatible with the insect brain,
      and is not dependent on top-down or executive control processing.

PMID- 30222736
TI  - Drug susceptibility testing of slowly growing non-tuberculous mycobacteria using
      slomyco test-system.
AB  - OBJECTIVE: The objective of the research was to assess the susceptibility of the
      slowly growing nontuberculous mycobacteria strains to the antimicrobial drugs
      used for mycobaterioses treatment using SLOMYCO test system. MATERIALS AND
      METHODS: We assessed 363 NTM strains: 177 MAC (161 M. avium, 16 M.
      intracellulare), 112 M. kansasii and 74 M. xenopi collected from the respiratory
      material of the patients were under the treatment or under diagnostic procedures
      at our Center, affiliates and the diagnostic department in 2010-2016. Drug
      sucseptibility for NTM was tested using the Sensititre SLOWMYCO system (TREK
      DIAGNOSTIC Systems Ltd., UK). MICs were established by microdilutions in Mueller
      Hinton broth on polystyrene 96-well plates. The statistical analysis was done
      using the StatGraphics Plus 5.0 software. The data were compared pairwise using
      Pearson chi2 test with Yates correction. 95% confidence interval (CI) were
      calculated. Statistically significant differences were considered for p <0.05.
      Log-rank test and Kaplan-Meier curves were used to assess the concentration
      dependent surveillance probability. RESULTS: The statistically significant
      differences were revealed in sensitivity/resistance isolates of M. avium and M.
      intracellulare: M. avium strains were resistant to higher concentrations of
      amikacin, clarithromycin, linezolid and streptomycin (p <0.01); M. intracellulare
      strains were resistant to higher concentrations of ethionamide (p <0.05). The
      isolates of M. avium were significantly more resistant than M. kansasii to
      amikacin, doxycycline, isoniazid, clarithromycin, linezolid, moxifloxacin,
      rifabutin, rifampicin, streptomycin, trimethoprim/sulfamethoxazole,
      ciprofloxacin, ethambutol, ethionamide (visible growth of M. avium were inhibited
      by higher drug concentrations, p <0.01). The isolates of M. avium showed
      significantly higher resistance than M. xenopi to amikacin, doxycycline,
      isoniazid, clarithromycin, linezolid, moxifloxacin, rifampicin, streptomycin,
      trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide
      (visible growth of M. avium were inhibited by higher drug concentrations, p
      <0.01). Statistically significant differences in the dynamics of the response to
      the antibacterial effects of isoniazid, linezolid, moxifloxacin, rifampicin,
      trimethoprim/sulfamethoxazole, ethambutol, and ethionamide were found for M.
      intracellulare and M. xenopi (complete inhibition of the visible growth of M.
      intracellulare required higher drugs concentrations, p <0, 05). Comparison of the
      Kaplan-Meyer curves revealed statistically significant differences in survialence
      probability of M. kansasii and M. xenopi for amikacin, doxycycline, rifampicin,
      trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide (a
      higher number of isolates of M. xenopi were inhibited by low drugs
      concentrations, p <0.05). CONCLUSIONS: Our data show that M. avium and M.
      intracellulare were more resistant to the majority of the studied drugs than M.
      kansasii and M. xenopi.

PMID- 30222737
TI  - Topoisomerases I and III inhibit R-loop formation to prevent unregulated
      replication in the chromosomal Ter region of Escherichia coli.
AB  - Type 1A topoisomerases (topos) are the only ubiquitous topos. E. coli has two
      type 1A topos, topo I (topA) and topo III (topB). Topo I relaxes negative
      supercoiling in part to inhibit R-loop formation. To grow, topA mutants acquire
      compensatory mutations, base substitutions in gyrA or gyrB (gyrase) or
      amplifications of a DNA region including parC and parE (topo IV). topB mutants
      grow normally and topo III binds tightly to single-stranded DNA. What functions
      topo I and III share in vivo and how cells lacking these important enzymes can
      survive is unclear. Previously, a gyrB(Ts) compensatory mutation was used to
      construct topA topB null mutants. These mutants form very long filaments and
      accumulate diffuse DNA, phenotypes that appears to be related to replication from
      R-loops. Here, next generation sequencing and qPCR for marker frequency analysis
      were used to further define the functions of type 1A topos. The results reveal
      the presence of a RNase HI-sensitive origin of replication in the terminus (Ter)
      region of the chromosome that is more active in topA topB cells than in topA and
      rnhA (RNase HI) null cells. The S9.6 antibodies specific to DNA:RNA hybrids were
      used in dot-blot experiments to show the accumulation of R-loops in rnhA, topA
      and topA topB null cells. Moreover topA topB gyrB(Ts) strains, but not a topA
      gyrB(Ts) strain, were found to carry a parC parE amplification. When a topA
      gyrB(Ts) mutant carried a plasmid producing topo IV, topB null transductants did
      not have parC parE amplifications. Altogether, the data indicate that in E. coli
      type 1A topos are required to inhibit R-loop formation/accumulation mostly to
      prevent unregulated replication in Ter, and that they are essential to prevent
      excess negative supercoiling and its detrimental effects on cell growth and
      survival.

PMID- 30222738
TI  - Albumin and hemoglobin adducts of estrogen quinone as biomarkers for early
      detection of breast cancer.
AB  - Cumulative estrogen concentration is an important determinant of the risk of
      developing breast cancer. Estrogen carcinogenesis is attributed to the
      combination of receptor-driven mitogenesis and DNA damage induced by quinonoid
      metabolites of estrogen. The present study was focused on developing an improved
      breast cancer prediction model using estrogen quinone-protein adduct
      concentrations. Blood samples from 152 breast cancer patients and 71 healthy
      women were collected, and albumin (Alb) and hemoglobin (Hb) adducts of estrogen
      3,4-quinone and estrogen-2,3-quinone were extracted and evaluated as potential
      biomarkers of breast cancer. A multilayer perceptron (MLP) was used as the
      predictor model and the resultant prediction of breast cancer was more accurate
      than other existing detection methods. A MLP using the logarithm of the
      concentrations of the estrogen quinone-derived adducts (four input nodes, 10
      hidden nodes, and one output node) was used to predict breast cancer risk with
      accuracy close to 100% and area under curve (AUC) close to one. The AUC value of
      one showed that both data sets were separable. We conclude that Alb and Hb
      adducts of estrogen quinones are promising biomarkers for the early detection of
      breast cancer.

PMID- 30222741
TI  - The assessment of work endurance in disability evaluations across European
      countries.
AB  - PURPOSE: Chronic disease is often associated with a reduced energy level, which
      limits the capacity to work full-time. This study aims to investigate whether the
      construct work endurance is part of disability assessment in European countries
      and what assessment procedures are used. We defined work endurance as the ability
      to sustain working activities for a number of hours per day and per week.
      MATERIALS AND METHODS: We conducted a survey using two self-constructed
      questionnaires. We addressed 35 experts from 19 countries through the European
      Union of Medicine in Assurance and Social Security (EUMASS). We gathered
      descriptive data on various aspects of (the assessment of) work endurance.
      RESULTS: Experts from 16 countries responded. In most countries work endurance is
      assessed. We found few professional guidelines specific for the assessment of
      work endurance. Both somatic and mental diseases may cause limited work
      endurance. Methods to assess work endurance vary, objective methods rating as
      most suitable. Almost half of the countries report controversies on the
      assessment of work endurance. CONCLUSIONS: Work endurance is recognised and
      assessed as an aspect of work disability assessment in Europe. However,
      controversies exist and evidence based guidelines, including reliable and valid
      methods to assess work endurance, are lacking.

PMID- 30222739
TI  - Phospho-proteomic analysis of primary human colon epithelial cells during the
      early Trypanosoma cruzi infection phase.
AB  - The protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease,
      causes severe morbidity and mortality in afflicted individuals. About 30% of T.
      cruzi-infected individuals present with cardiac, gastrointestinal tract, and/or
      neurological disorders. Megacolon, one of the major pathologies of Chagas
      disease, is accompanied by gastrointestinal motility disorders. The molecular
      mechanism of T. cruzi-mediated megacolon in Chagas disease is currently unknown.
      To decipher the molecular mechanism of T. cruzi-induced alteration in the colon
      during the early infection phase, we exposed primary human colonic epithelial
      cells (HCoEpiC) to invasive T. cruzi trypomastigotes at multiple time points to
      determine changes in the phosphoprotein networks in the cells following infection
      using proteome profiler Human phospho-kinase arrays. We found significant changes
      in the phosphorylation pattern that can mediate cellular deregulations in colonic
      epithelial cells after infection. We detected a significant increase in the
      levels of phosphorylated heat shock protein (p-HSP) 27 and transcription factors
      that regulate various cellular functions, including c-Jun and CREB. Our study
      confirmed significant upregulation of phospho (p-) Akt S473, p-JNK, which may
      directly or indirectly modulate CREB and c-Jun phosphorylation, respectively. We
      also observed increased levels of phosphorylated CREB and c-Jun in the nucleus.
      Furthermore, we found that p-c-Jun and p-CREB co-localized in the nucleus at 180
      minutes post infection, with a maximum Pearson correlation coefficient of 0.76+/
      0.02. Increased p-c-Jun and p-CREB have been linked to inflammatory and
      profibrotic responses. T. cruzi infection of HCoEpiC induces an increased
      expression of thrombospondin-1 (TSP-1), which is fibrogenic at elevated levels.
      We also found that T. cruzi infection modulates the expression of NF-kB and JAK2
      STAT1 signaling molecules which can increase pro-inflammatory flux.
      Bioinformatics analysis of the phosphoprotein networks derived using the phospho
      protein data serves as a blueprint for T. cruzi-mediated cellular transformation
      of primary human colonic cells during the early phase of T. cruzi infection.

PMID- 30222742
TI  - Correction: A method to quantify mechanobiologic forces during zebrafish cardiac
      development using 4-D light sheet imaging and computational modeling.
AB  - [This corrects the article DOI: 10.1371/journal.pcbi.1005828.].

PMID- 30222740
TI  - The physiological variability of channel density in hippocampal CA1 pyramidal
      cells and interneurons explored using a unified data-driven modeling workflow.
AB  - Every neuron is part of a network, exerting its function by transforming multiple
      spatiotemporal synaptic input patterns into a single spiking output. This
      function is specified by the particular shape and passive electrical properties
      of the neuronal membrane, and the composition and spatial distribution of ion
      channels across its processes. For a variety of physiological or pathological
      reasons, the intrinsic input/output function may change during a neuron's
      lifetime. This process results in high variability in the peak specific
      conductance of ion channels in individual neurons. The mechanisms responsible for
      this variability are not well understood, although there are clear indications
      from experiments and modeling that degeneracy and correlation among multiple
      channels may be involved. Here, we studied this issue in biophysical models of
      hippocampal CA1 pyramidal neurons and interneurons. Using a unified data-driven
      simulation workflow and starting from a set of experimental recordings and
      morphological reconstructions obtained from rats, we built and analyzed several
      ensembles of morphologically and biophysically accurate single cell models with
      intrinsic electrophysiological properties consistent with experimental findings.
      The results suggest that the set of conductances expressed in any given
      hippocampal neuron may be considered as belonging to two groups: one subset is
      responsible for the major characteristics of the firing behavior in each
      population and the other is responsible for a robust degeneracy. Analysis of the
      model neurons suggests several experimentally testable predictions related to the
      combination and relative proportion of the different conductances that should be
      expressed on the membrane of different types of neurons for them to fulfill their
      role in the hippocampus circuitry.

PMID- 30222743
TI  - Molecular epidemiology and drug resistance patterns of Mycobacterium tuberculosis
      complex isolates from university students and the local community in Eastern
      Ethiopia.
AB  - BACKGROUND: Previous studies suggest the burden of pulmonary tuberculosis (PTB)
      in Ethiopia may be greater in university students relative to the overall
      population. However, little is known about the transmission dynamics of PTB among
      students and members of the communities surrounding university campuses in
      Eastern Ethiopia. METHODS: A cross sectional study was conducted in Eastern
      Ethiopia among prevalent culture-confirmed PTB cases from university students (n
      = 36) and community members diagnosed at one of four hospitals (n = 152) serving
      the surrounding area. Drug susceptibility testing (DST) was performed on
      Mycobacterium tuberculosis complex (MTBC) isolates using BD Bactec MGIT 960 and
      molecular genotyping was performed using spoligotyping and 24-loci MIRU-VNTR.
      MTBC strains with Identical genotyping patterns were assigned to molecular
      clusters as surrogate marker for recent transmission and further contact tracing
      was initiated among clustered patients. RESULTS: Among all study participants,
      four MTBC lineages and 11 sub-lineages were identified, with Ethiopia_3 (Euro
      American lineage) being most common sub-lineage (29.4%) in both cohorts and
      associated with strain clustering (P = 0.016). We further identified 13 (8.1%)
      strains phylogenetically closely related to Ethiopia_3 but with a distinct
      Spoligotyping pattern and designated as Ethiopia_4. The clustering rate of MTBC
      strains was 52.9% for university students and 66.7% for community members with a
      Recent Transmission Index (RTI) of 17.6% and 48.4%, respectively. Female gender,
      urban residence, and new TB cases were significantly associated with strain
      clustering (P<0.05). Forty-eight (30%) of the study participants were resistant
      to one or more first line anti TB drugs, three patients were classified as
      multidrug resistant (MDR). CONCLUSION: We found evidence for recent transmission
      of PTB among Ethiopian university students and the local community in Eastern
      Ethiopia, mainly linked to strains classified as Ethiopia_3 sub lineage. Drug
      resistance didn't have a major impact on recent transmission but comprehensive
      molecular surveillance in combination with drug resistance profiling of MTBC
      strains is desirable to better characterize TB transmission dynamics in high risk
      congregate living environments such as university campuses and guide regional TB
      control programs.

PMID- 30222744
TI  - In vitro investigation of the ruminal digestion kinetics of different nitrogen
      fractions of 15N-labelled timothy forage.
AB  - An in vitro method based on 15N-labelled forage nitrogen (N) was developed to
      study ruminal N metabolism of soluble N (SN), insoluble N (ISN) and neutral
      detergent insoluble N (NDIN) fractions of timothy forage. Timothy grass was grown
      on replicated experimental plots with one plot receiving 15N-labelled and the
      other unlabelled N fertilizer. Harvested grass was preserved as dried grass or as
      formic acid treated or untreated silage. The intact forages and their
      corresponding N fractions were incubated in buffered rumen fluid in vitro to
      determine degradation parameters based on the 15N fluxes between labelled feed N
      and ammonia N pools. A high percentage (25-38%) of 15N-labelled ammonia
      disappeared from ammonia N pool during the first 15 min of incubation. Microbial
      uptake of dried grass SN fraction was higher than of silage SN fractions.
      Fractional degradation rates of SN from formic acid treated silage, untreated
      silage and dried grass during the first 6 hours of incubation were 0.145, 0.125
      and 0.115 /h, respectively. By the end of the incubation period (28 h), 69, 66
      and 43%, of the SN fraction of formic acid treated silage, untreated silage and
      dried grass, respectively were recovered as ammonia. The percentage of ISN
      fractions degraded to ammonia N were 9, 34 and 27%, respectively. Based on the
      changes in 15N-labelled ammonia N pool in blank incubation and appearance of 15N
      to ammonia N pool from 15N-labelled NDIN fractions, it was estimated that a
      significant portion of microbial lysis occurred when incubations were carried out
      for longer than 20 hours. With dried grass the contribution of ammonia N for
      microbial N synthesis was greater than with silages. Use of 15N-labelled forages
      together with this in vitro method is a promising technique for determining
      soluble N degradation parameters, but it requires further development to be used
      for determining degradation parameters of insoluble N fractions and work with
      whole feeds.

PMID- 30222745
TI  - Home ranges and movements of resident graylag geese (Anser anser) in breeding and
      winter habitats in Bavaria, South Germany.
AB  - In several countries in northwestern Europe, the number of resident greylag geese
      (Anser anser) has increased by up to 20% a year over the last few decades. The
      increasing numbers of geese are causing problems in tourism and agriculture. The
      number of resident greylag geese visiting the Altmuehlsee lake, a recreational
      area in the south of Germany, has also increased, especially in June and July.
      However, the geese leave the lake again at the beginning of August. 30 adult
      greylag geese were banded with telemetry transmitters during molting at the
      Altmuehlsee lake to determine when the geese leave the lake in August and what
      structures they need in their winter habitat. The distances the greylag geese
      flew from their resting sites to foraging sites were calculated, as well as the
      size of their home ranges and the proportions of each habitat type in the home
      range. It was found that the greylag geese used small home ranges while rearing
      their young, and fed close to the water. After molting, the size of their home
      ranges increased. They fed on fields and meadows around the lake. In the winter
      habitat, the geese also had a small home range, and they preferred eating grain
      and corn and the availability of an open body of water. In addition, one group of
      geese remained in the city of Munich during the winter, benefiting from
      supplementary food from people. This information helps us to understand the
      different requirements of resident greylag geese. It can be used to inform
      management decisions aimed at preventing agricultural damage. Special goose areas
      can for example be designated for the different periods in a goose's life cycle.

PMID- 30222747
TI  - Corneal complications following Post Kala-azar Dermal Leishmaniasis treatment.
AB  - Post Kala-azar Dermal Leishmaniasis (PKDL) is a sequel of Visceral Leishmaniasis
      (VL). The patients act as a reservoir for the causative parasite (i.e. Leishmania
      donovani) and thus should be diagnosed and treated with the utmost urgency to
      prevent the transmission of the disease. In this study, we tried to report the
      first instances of corneal complications supposedly associated with Miltefosine
      (MF), in PKDL patients and the probable pathophysiology of such events. The
      recently rejuvenated National Kala-azar Elimination Program in Bangladesh has put
      great emphasis on monitoring all the leishmaniasis patients to investigate
      possible adverse drug reactions (ADR). A total of 194 patients have received
      Miltefosine for the treatment of Post Kala-azar Dermal Leishmaniasis. So far five
      patients were found to have developed unilateral ophthalmic complications during
      the periods from May 2016 to October 2017, after being treated with MF for PKDL.
      Unfortunately, one of whom had to go through complete evisceration of the
      affected eyeball. Despite the fact that MF is the only oral formulation of choice
      to treat PKDL, occurrences of such unexpected ADRs after MF administration urges
      the exploration of the pathogenesis of such incidents and determine measures to
      avert such occurrences from happening in future.

PMID- 30222746
TI  - Model-based spatial navigation in the hippocampus-ventral striatum circuit: A
      computational analysis.
AB  - While the neurobiology of simple and habitual choices is relatively well known,
      our current understanding of goal-directed choices and planning in the brain is
      still limited. Theoretical work suggests that goal-directed computations can be
      productively associated to model-based (reinforcement learning) computations, yet
      a detailed mapping between computational processes and neuronal circuits remains
      to be fully established. Here we report a computational analysis that aligns
      Bayesian nonparametrics and model-based reinforcement learning (MB-RL) to the
      functioning of the hippocampus (HC) and the ventral striatum (vStr)-a neuronal
      circuit that increasingly recognized to be an appropriate model system to
      understand goal-directed (spatial) decisions and planning mechanisms in the
      brain. We test the MB-RL agent in a contextual conditioning task that depends on
      intact hippocampus and ventral striatal (shell) function and show that it solves
      the task while showing key behavioral and neuronal signatures of the HC-vStr
      circuit. Our simulations also explore the benefits of biological forms of look
      ahead prediction (forward sweeps) during both learning and control. This article
      thus contributes to fill the gap between our current understanding of
      computational algorithms and biological realizations of (model-based)
      reinforcement learning.

PMID- 30222748
TI  - Evolutionary footprint of epistasis.
AB  - Variation of an inherited trait across a population cannot be explained by
      additive contributions of relevant genes, due to epigenetic effects and
      biochemical interactions (epistasis). Detecting epistasis in genomic data still
      represents a significant challenge that requires a better understanding of
      epistasis from the mechanistic point of view. Using a standard Wright-Fisher
      model of bi-allelic asexual population, we study how compensatory epistasis
      affects the process of adaptation. The main result is a universal relationship
      between four haplotype frequencies of a single site pair in a genome, which
      depends only on the epistasis strength of the pair defined regarding Darwinian
      fitness. We demonstrate the existence, at any time point, of a quasi-equilibrium
      between epistasis and disorder (entropy) caused by random genetic drift and
      mutation. We verify the accuracy of these analytic results by Monte-Carlo
      simulation over a broad range of parameters, including the topology of the
      interacting network. Thus, epistasis assists the evolutionary transit through
      evolutionary hurdles leaving marks at the level of haplotype disequilibrium. The
      method allows determining selection coefficient for each site and the epistasis
      strength of each pair from a sequence set. The resulting ability to detect
      clusters of deleterious mutation close to full compensation is essential for
      biomedical applications. These findings help to understand the role of epistasis
      in multiple compensatory mutations in viral resistance to antivirals and immune
      response.

PMID- 30222749
TI  - PCR-RFLP screening of polymorphisms associated with benzimidazole resistance in
      Necator americanus and Ascaris lumbricoides from different geographical regions
      in Brazil.
AB  - Ascaris lumbricoides and Necator americanus are soil-transmitted parasites with
      global geographic distribution, and they represent some of the most common and
      neglected infections in the world. Periodic treatment with mass drug
      administration (MDA) in endemic areas is the recommended action put forth by the
      World Health Organization. However, MDA can cause the selection of subpopulations
      that possess the genetic ability to overcome the mechanism of drug action. In
      fact, beta-tubulin gene mutations (codons 167, 198 and 200) are correlated with
      benzimidazole resistance in nematodes of veterinary importance. It is possible
      that these SNPs also have strong correlation with treatment resistance in the
      human geohelminths A. lumbricoides, Trichuris trichiura and hookworms. Here, we
      aimed to investigate the presence of some of these canonical molecular markers
      associated with parasite resistance to benzimidazole in N. americanus and A.
      lumbricoides collected from six Brazilian states. Nested-PCR and PCR-RFLP were
      used to detect mutations at codons 167 and 198 in 601 individual eggs of A.
      lumbricoides collected from 62 human stool samples; however, no mutations were
      found. Codons 198 and 200 were tested in 552 N. americanus eggs collected from 48
      patients using the same methodology, which presented a relative frequency of 1.4%
      and 1.1%, respectively. The presence of these SNPs in N. americanus eggs is an
      important finding, indicating that with high benzimidazole drug pressure there is
      potential for benzimidazole resistance to be selected in this hookworm. However,
      at these low frequencies it does not indicate that there is at present any
      benzimidazole resistance problem. This is the first systematic study performed in
      South America, and the study yielded a landscape of the genetic variants in the
      beta-tubulin gene and anthelmintic resistance to soil-transmitted parasites
      detected by a simple, rapid and affordable genotyping assay of individual eggs.

PMID- 30222750
TI  - Clinico-pathological significance of exosome marker CD63 expression on cancer
      cells and stromal cells in gastric cancer.
AB  - BACKGROUND: It has been reported that CD63, an exosome marker, is expressed in
      solid cancer tissues. However, its significance in patients with gastric cancer
      has not been clarified. Exosomes derived from cancer cells and stromal cells
      might play an important role in the intracellular communications involved in the
      development of carcinoma. This study aimed to clarify the relationship between
      CD63 expression in cancer cells and stromal cells and clinical-pathologic
      factors. METHODS: A total of 595 gastric cancer patients were enrolled in this
      study. CD63 expression in cancer cells and stromal cells was analyzed by
      immunohistochemistry. The correlations between CD63 expression and several
      clinicopathological factors were investigated. RESULTS: CD63 expression was
      mainly observed on the cell membranes of cancer cells, and in the cytoplasm of
      stromal cells. Of 595 patients, 247 cases had CD63-positive cancer cells, and 107
      cases had CD63-positive stromal cells. Cases with CD63-positive cancer cells were
      significantly correlated with scirrhous-type gastric cancer, tumor depth, lymph
      node metastasis, lymphatic invasion, and tumor size. Cases with CD63-positive
      stromal cells were significantly correlated with age (>=65), tumor depth (T3-4),
      lymphatic invasion, and tumor size (>= 5 cm). The 5-year survival rate was
      significantly lower (p<0.001) in patients with CD63-positive than CD63-negative
      tumors. Multivariate analysis showed that CD63 expression in cancer cells was a
      significant independent prognostic factor in patients with gastric cancer.
      CONCLUSION: CD63 might be a prognostic marker for patients with gastric cancer.
      CD63-positive exosomes might be associated with the interaction between stromal
      cells and cancer cells.

PMID- 30222752
TI  - General equilibrium with endogenous trading constraints.
AB  - In a competitive model where agents are subject to endogenous trading
      constraints, we make the access to financial trade dependent on prices and
      consumption decisions. Our framework is compatible with the existence of both
      credit market segmentation and market exclusion. In this context, we show
      equilibrium existence in two scenarios. In the first one, individuals can fully
      hedge the payments of segmented financial contracts by trading unsegmented
      assets. In the second one, it is assumed that agents may compensate with
      increments in present demand the losses of well-being generated by reductions of
      future consumption.

PMID- 30222751
TI  - The association of rainfall and Buruli ulcer in southeastern Australia.
AB  - BACKGROUND: Buruli ulcer has been increasing in incidence in southeastern
      Australia with unclear transmission mechanisms. We aimed to investigate the link
      between rainfall and case numbers in two endemic areas of the state of Victoria;
      the Bellarine and Mornington Peninsulas. METHODOLOGY: We created yearly and
      monthly graphs comparing rainfall with local Buruli ulcer incidence for the
      period 2004-2016 by endemic region and then considered a range of time lag
      intervals of 0-24 months to investigate patterns of correlation. CONCLUSIONS:
      Optimal positive correlation for the Bellarine Peninsula occurred with a 12-month
      prior rainfall lag, however, no significant correlation was observed on the
      Mornington Peninsula for any time lag. These results provide an update in
      evidence to further explore transmission mechanisms which may differ between
      these geographically proximate endemic regions.

PMID- 30222753
TI  - Second language acquisition effects of a primary physical education intervention:
      A pilot study with young refugees.
AB  - BACKGROUND: A physical education (PE) intervention for young refugees was
      designed combining physical activity within the context of primary PE games with
      second language learning activities in German. The intervention was based on
      theoretical implications from the field of second language acquisition and
      evidence for positive effects of physical activity on cognitive outcomes (e.g.
      language acquisition). The aim of this study was to analyze short term effects on
      second language acquisition. METHODS: Sixty-one young refugees were included in
      the study (age: 8.5 +/- 1.4 years). The intervention group participated in
      language-enriched PE lessons based on an elaborated approach to second language
      learning acquisition. The control group did not receive any treatment. Both
      groups were pre-and post-tested in domain specific vocabulary, listening
      comprehension and use of local prepositions within the context of primary PE
      games. RESULTS: Results from linear mixed-effect modelling suggest that the
      intervention group significantly improved domain specific vocabulary and
      listening comprehension in comparison to the control group. CONCLUSIONS: The
      intervention was successful since the PE lessons contributed to the second
      language acquisition of young refugees. Therefore, this learning approach might
      also be useful for physical activity based second language learning activities in
      other PE contexts for early second language learners in primary school.

PMID- 30222754
TI  - Destabilization of the von Willebrand factor A2 domain under oxidizing conditions
      investigated by molecular dynamics simulations.
AB  - The protein von Willebrand factor (VWF) is key for the adhesion of blood
      platelets to sites of vascular injury. Recent studies have shown that the release
      of oxidative agents during inflammation increases the platelet-tethering activity
      of VWF contributing to a pro-thrombotic state. This has been linked to the
      oxidation of methionine residues in the A1, A2 and A3 domains of VWF. The A1
      domain binds to platelet surface receptors glycoprotein Ib alpha (GpIbalpha).
      This interaction has been shown to be inhibited under static conditions by the
      neighboring A2 domain. Tensile force exerted by blood flow unfolds the A2 domain
      normally leading to its cleavage by the metalloprotease ADAMTS13 preventing
      pathological thrombus formation. However, oxidizing conditions inhibit
      proteolysis through ADAMTS13. Here, molecular dynamics simulations tested the
      hypothesis whether methionine oxidation induced by inflammatory conditions favors
      unfolding of the A2 domain contributing to the experimentally observed activation
      of VWF. The results indicate that oxidation of methionine residues located near
      the C-terminal helix of the A2 domain reduce the force necessary to initiate
      unfolding. Furthermore, oxidation of methionine residues shifts the thermodynamic
      equilibrium of the A2 domain fold towards the denatured state. This work suggests
      a mechanism whereby oxidation reduces the kinetic and thermodynamic stability of
      the A2 domain removing its inhibitory function on the binding of the A1 domain to
      GpIbalpha.

PMID- 30222755
TI  - Comparison of strain elastography, point shear wave elastography using acoustic
      radiation force impulse imaging and 2D-shear wave elastography for the
      differentiation of thyroid nodules.
AB  - PURPOSE: The aim of the study was to compare three different elastography
      methods, namely Strain Elastography (SE), Point Shear-Wave Elastography (pSWE)
      using Acoustic Radiation Force Impulse (ARFI)-Imaging and 2D-Shear Wave
      Elastography (2D-SWE), in the same study population for the differentiation of
      thyroid nodules. MATERIALS AND METHODS: All patients received a conventional
      ultrasound scan, SE and 2D-SWE, and all patients except for two received ARFI
      Imaging. Cytology/histology of thyroid nodules was used as a reference method. SE
      measures the relative stiffness within the region of interest (ROI) using the
      surrounding tissue as reference tissue. ARFI mechanically excites the tissue at
      the ROI using acoustic pulses to generate localized tissue displacements. 2D-SWE
      measures tissue elasticity using the velocity of many shear waves as they
      propagate through the tissue. RESULTS: 84 nodules (73 benign and 11 malignant) in
      62 patients were analyzed. Sensitivity, specificity and NPV of SE were 73%, 70%
      and 94%, respectively. Sensitivity, specificity and NPV of ARFI and 2D-SWE were
      90%, 79%, 98% and 73%, 67%, 94% respectively, using a cut-off value of 1.98m/s
      for ARFI and 2.65m/s (21.07kPa) for 2D-SWE. The AUROC (Area under the Receiver
      Operating Characteristic) of SE, ARFI and 2D-SWE for the diagnosis of malignant
      thyroid nodules were 52%, 86% and 71%, respectively. A significant difference in
      AUROC was found between SE and ARFI (p = 0.008), while no significant difference
      was found between ARFI and SWE (86% vs. 71%, p = 0.31), or SWE and SE (71% vs.
      52%, p = 0.26). CONCLUSION: pSWE using ARFI and 2D-SWE showed comparable results
      for the differentiation of thyroid nodules. ARFI was superior to elastography
      using SE.

PMID- 30222756
TI  - Estimating the efficacy of community-wide use of systemic insecticides in dogs to
      control zoonotic visceral leishmaniasis: A modelling study in a Brazilian
      scenario.
AB  - Systemic insecticides in dogs have been suggested as a public health intervention
      to prevent human cases of Zoonotic Visceral Leishmaniasis (ZVL). But, currently
      there are no systemic insecticides for dogs registered against zoo-anthropophilic
      pool blood feeding phlebotomine flies. We predict the impact of community-wide
      use of systemic insecticide in dog populations as a public health measure to
      control transmission of Leishmania infantum to humans using a mathematical model.
      We developed a Susceptible-Exposed-Infected (SEI) compartmental model to describe
      L. infantum transmission dynamics in dogs, with a vectorial capacity term to
      represent transmission between L. infantum-hosting dogs via phlebotomine flies.
      For Infected (I) dogs two levels of infectiousness were modelled, high
      infectiousness and low infectiousness. Human incidence was estimated through its
      relationship to infection in the dog population. We evaluated outcomes from a
      wide range of scenarios comprising different combinations of initial insecticide
      efficacy, duration of insecticide efficacy over time, and proportion of the dog
      population treated (60%, 70% & 80%). The same reduction in human infection
      incidence can be achieved via different combinations of insecticide efficacy,
      duration and dog coverage. For example, a systemic insecticide with an initial
      efficacy of 80% and 6 months above 65% efficacy would require treating at least
      70% of the dogs to reduce the human infection incidence by 50%. Sensitivity
      analysis showed that the model outcome was most sensitive to baseline values of
      phlebotomine fly daily survival rate and insecticide coverage. Community-wide use
      of systemic insecticides applied to the "L. infantum canine reservoir" can
      significantly reduce human incidence of L. infantum infection. The results of
      this mathematical model can help defining the insecticide target product profile
      and how the insecticide should be applied to maximise effectiveness.

PMID- 30222757
TI  - Copper-caused oxidative stress triggers the activation of antioxidant enzymes via
      ZmMPK3 in maize leaves.
AB  - Copper (Cu) is a necessary trace element participated in many physiological
      processes in plants. But excessive Cu2+ is toxic, which can activate
      intracellular signals that lead to cellular damage. The mitogen-activated protein
      kinase (MAPK) cascade is at the center of cell signal transduction and has been
      reported to be involved in stress-related signaling pathways. ZmMPK3, a kind of
      MAPKs in maize cells, can be activated by diverse abiotic stresses. In the
      present study, we investigated the effects of Cu2+ on hydrogen peroxide (H2O2)
      level, ZmMPK3 activity as well as the activities of antioxidant enzymes
      superoxide dismutase (SOD), catalase (CAT) and ascorbic acid peroxidase (APX)
      using maize leaf as an experimental model. The results demonstrated that acute
      Cu2+ exposure for 24 hours led to rapid increases of H2O2 level and the increase
      in ZmMPK3 activity as well as the total activities of antioxidant enzymes SOD,
      CAT and APX. H2O2 scavenger, dimethylthiourea (DMTU), effectively inhibited the
      Cu2+-increased H2O2 level and the activity of ZmMPK3 as well as the activities of
      the antioxidant enzymes SOD, CAT and APX. Pre-treatment with the MAPK inhibitor,
      PD98059, significantly blocked the Cu2+-increased activities of ZmMPK3, CAT, APX
      and SOD, but didn't affect the accumulation of H2O2. Our results suggest that
      Cu2+ causes oxidative stress to the maize leaves which then activates defense
      antioxidant enzymes via MAPK pathway. Thus, the signaling pathway is Cu2+-H2O2
      ZmMPK3-antioxidant enzymes.

PMID- 30222758
TI  - Towards elimination of lymphatic filariasis in southeastern Madagascar: Successes
      and challenges for interrupting transmission.
AB  - INTRODUCTION: A global strategy of mass drug administration (MDA) has greatly
      reduced the burden of lymphatic filariasis (LF) in endemic countries. In
      Madagascar, the National Programme to eliminate LF has scaled-up annual MDA of
      albendazole and diethylcarbamazine across the country in the last decade, but its
      impact on LF transmission has never been reported. The objective of this study
      was to evaluate progress towards LF elimination in southeastern Madagascar.
      METHODS: Three different surveys were carried out in parallel in four health
      districts of the Vatovavy Fitovinany region in 2016: i) a school-based
      transmission assessment survey (TAS) in the districts of Manakara Atsimo,
      Mananjary, and Vohipeno (following a successful pre-TAS in 2013); ii) a district
      representative community prevalence survey in Ifanadiana district; and iii) a
      community prevalence survey in sentinel and spot-check sites of these four
      districts. LF infection was assessed using the Alere Filariasis Test Strips,
      which detect circulating filarial antigens (CFA) of adult worms. A brief
      knowledge, attitudes and practices questionnaire was included in the community
      surveys. PRINCIPAL FINDINGS: None of the 1,825 children sampled in the TAS, and
      only one in 1,306 children from sentinel and spot-check sites, tested positive to
      CFA. However, CFA prevalence rate in individuals older than 15 years was still
      high in two of these three districts, at 3.5 and 9.7% in Mananjary and Vohipeno,
      respectively. Overall CFA prevalence in sentinel and spot-check sites of these
      three districts was 2.80% (N = 2,707), but only two individuals had detectable
      levels of microfilaraemia (0.06%). Prevalence rate estimates for Ifanadiana were
      substantially higher in the district-representative survey (15.8%; N = 545) than
      in sentinel and spot-check sites (0.8%; N = 618). Only 51.2% of individuals
      surveyed in these four districts reported taking MDA in the last year, and 42.2%
      reported knowing about LF. CONCLUSIONS: Although TAS results suggest that MDA can
      be stopped in three districts of southeastern Madagascar, the adult population
      still presents high CFA prevalence levels. This discordance raises important
      questions about the TAS procedures and the interpretation of their results.

PMID- 30222759
TI  - Association of tooth loss with liver cancer incidence and chronic liver disease
      mortality in a rural Chinese population.
AB  - BACKGROUND: Tooth loss has been reported to be associated with the risk of liver
      cancer in several prior studies in economically advantaged countries. Whether
      this relationship is also evident in economically disadvantaged populations is
      not known. METHODS: We analyzed data from the Nutrition Intervention Trials, two
      randomized placebo-controlled trials of vitamin/mineral supplementation in
      Linxian, China. Participants who reported having lost permanent teeth were
      examined to determine the number of teeth remaining. In the 30-year follow-up
      period, 329 liver cancers were diagnosed and 368 chronic liver disease deaths
      occurred. Tooth loss was categorized based on loess smoothed age-specific
      predicted quartiles. Cox proportional hazards regression was used to estimate
      hazard ratios (HRs) and 95% confidence intervals (CIs) for the two outcomes.
      RESULTS: Overall, persons in the highest quartile of age-specific tooth loss had
      an increased risk of liver cancer (HR = 1.27, 95%CI: 0.96, 1.67) which was not
      statistically significant. Results varied by sex and body mass index (BMI),
      however. Women in the highest quartile of age-specific tooth loss had a
      significantly increased risk (HR = 1.64, 95%CI: 1.04, 2.59), while men did not
      (HR = 1.08, 95%CI = 0.75, 1.57), and persons with a BMI > 23.0 kg/m2 (HR = 1.71,
      95%CI: 1.00, 2.92) had a significantly increased risk, while persons with a BMI
      <23.0 kg/m2 did not (HR = 1.14, 95%CI: 0.82, 1.5). No relationships with chronic
      liver disease mortality were observed. CONCLUSIONS: In a rural, economically
      disadvantaged population, persons with the highest levels of age-specific tooth
      loss had an increased risk of liver cancer. The results, which were stronger
      among women and persons with greater BMI, suggest that periodontal disease may
      increase risk of liver cancer.

PMID- 30222760
TI  - QTL and QTL networks for cold tolerance at the reproductive stage detected using
      selective introgression in rice.
AB  - Low temperature stress is one of the major abiotic stresses limiting the
      productivity of Geng (japonica) rice grown the temperate regions as well as in
      tropical high lands worldwide. To develop rice varieties with improved cold
      tolerance (CT) at the reproductive stage, 84 BC2 CT introgression lines (ILs)
      were developed from five populations through backcross breeding. These CT ILs
      plus 310 random ILs from the same BC populations were used for dissecting genetic
      networks underlying CT in rice by detecting QTLs and functional genetic units
      (FGUs) contributing to CT. Seventeen major QTLs for CT were identified using five
      selective introgression populations and the method of segregation distortion. Of
      them, three QTLs were confirmed using the random populations and seven others
      locate in the regions with previously reported CT QTLs/genes. Using multi-locus
      probability tests and linkage disequilibrium (LD) analyses, 46 functional genetic
      units (FGUs) (37 single loci and 9 association groups or AGs) distributed in 37
      bins (~20%) across the rice genome for CT were detected. Together, each of the CT
      loci (bins) was detected in 1.7 populations, including 18 loci detected in two or
      more populations. Putative genetic networks (multi-locus structures) underlying
      CT were constructed based on strong non-random associations between or among
      donor alleles at the unlinked CT loci/FGUs identified in the CT ILs, suggesting
      the presence of strong epistasis among the detected CT loci. Our results
      demonstrated the power and usefulness of using selective introgression for
      simultaneous improvement and genetic dissection of complex traits such as CT in
      rice.

PMID- 30222761
TI  - Correction: miRNA independent hepacivirus variants suggest a strong evolutionary
      pressure to maintain miR-122 dependence.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1006694.].

PMID- 30222763
TI  - Correction: Kinetics of antibody responses to PfRH5-complex antigens in Ghanaian
      children with Plasmodium falciparum malaria.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0198371.].

PMID- 30222762
TI  - "She must have been sleeping around"...: Contextual interpretations of cervical
      cancer and views regarding HPV vaccination for adolescents in selected
      communities in Ibadan, Nigeria.
AB  - BACKGROUND: Human Papilloma virus (HPV) vaccines for adolescents are pivotal in
      the control of cervical cancer, the commonest women specific malignancy in sub
      Saharan Africa. Knowledge about cervical cancer have been reported to be low in
      Africa but expressed acceptability for HPV vaccines have been high. The reason
      for this mismatch is not clear. An understanding of the interpretation of
      cervical cancer and views about HPV vaccine are important as they can affect
      actual decision making regarding adolescents' uptake of HPV vaccine. This study
      explored contextual interpretations of stakeholders regarding cervical cancer and
      HPV vaccines for adolescents in five selected communities in Ibadan, Nigeria.
      METHODS: Qualitative data were collected through twenty focus group discussions
      among parents of adolescents, religious and traditional leaders, school teachers
      and adolescents; and four key informant interviews with the identified
      traditional healers in the selected communities. Constant comparison analysis was
      done after transcription. RESULTS: Almost every group had at least one person who
      had seen a cervical cancer patient. Cervical cancer was widely viewed as being
      caused by promiscuity of women while older participants believed that the
      alteration of lifestyle by civilization was a major contributory factor. There
      was also a general notion that it was due to a curse. The role of HPV was
      generally not known. Most participants were favourable towards HPV immunization
      for adolescents but traditional healers and some religious leaders were not. The
      high cost of the vaccines and possibility of side effects where the main concerns
      about the introduction of HPV vaccine. Decision to take the vaccine rest with the
      fathers whose views were heavily influenced by traditional and religious leaders.
      CONCLUSIONS: Awareness about cervical cancer may not be as low as earlier
      reported and there were many misconceptions about cervical cancer in the study
      communities. It is important to address these misconceptions to ensure successful
      introduction of HPV vaccine for adolescents in future.

PMID- 30222764
TI  - Preservation of fatty acid signatures in three vertebrate species after six
      months of storage at various temperatures.
AB  - Fatty acid (FA) signatures (FAS) are important tools to assess the foraging
      ecology of wild animals. The present study was conducted to assess how well the
      general FAS and the proportions of individual FA are preserved in fat samples
      stored at different temperatures (-196, -80, -20, +4 and +20 degrees C). Using
      three species (laboratory rat, American mink and rainbow trout), FAS were
      determined immediately upon sampling. Thereafter, eight subsamples per storage
      temperature from the inner part of the sample unaffected by oxygen and light were
      re-analyzed after 1, 2, 3, 7, 28, 84 and 168 days. Each time the remaining sample
      was sealed in its vial after replacing air with nitrogen gas. The results were
      tested with the mixed model and discriminant analyses. Generally, the FAS were
      well preserved regardless of storage temperature, and only a few major FA showed
      significant changes even after the 6-month period at room temperature. After an
      initial first-day change in proportions, presumably due to post-mortem enzymatic
      activities, the remaining minor changes could not be clearly attributed to either
      further autolysis, decomposition or autoxidation. In the discriminant analysis,
      the species-specific differences dominated and remained distinct even after 6
      months. Furthermore, the analysis mostly classified the samples preserved at sub-
      and above-freezing temperatures separate from each other, and the general
      deviation from the initial analysis results was present as early as after 1 day.
      If FAS are to be analyzed in a very precise manner, the analysis should be
      performed immediately upon sampling. However, FAS remain adequately reliable for
      long periods of time even without preservation in deep freeze, widening the
      availability of potential samples for studies on foraging ecology and related
      disciplines.

PMID- 30222765
TI  - Ascertaining infectious disease burden through primary care clinic attendance
      among young Aboriginal children living in four remote communities in Western
      Australia.
AB  - Infectious diseases contribute a substantial burden of ill-health in Australia's
      Aboriginal children. Skin infections have been shown to be common in remote
      Aboriginal communities, particularly in the Northern Territory, Australia.
      However, primary care data on skin and other infectious diseases among Aboriginal
      children living in remote areas of Western Australia are limited. We conducted a
      retrospective review of clinic presentations of all children aged 0 to 5 years
      presenting to four clinics located in the Western Desert region of Western
      Australia between 2007 and 2012 to determine this burden at a local level.
      Infectious diseases accounted for almost 50% of all clinic presentations. Skin
      infections (sores, scabies and fungal infections) were the largest proportion
      (16%), with ear infections (15%) and upper respiratory infections (13%) also
      high. Skin infections remained high in all age groups; 72% of children presented
      at least once with skin infections. Scabies accounted for only 2% of all
      presentations, although one-quarter of children presented during the study for
      management of scabies. Skin sores accounted for 75% of the overall burden of skin
      infections. Improved public health measures targeting bacterial skin infections
      are needed to reduce this high burden of skin infections in Western Australia.

PMID- 30222767
TI  - Correction: Glioma IL13Ralpha2 Is Associated with Mesenchymal Signature Gene
      Expression and Poor Patient Prognosis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0077769.].

PMID- 30222766
TI  - Differentiation of human iPSCs into functional podocytes.
AB  - Podocytes play a critical role in glomerular barrier function, both in health and
      disease. However, in vivo terminally differentiated podocytes are difficult to be
      maintained in in vitro culture. Induced pluripotent stem cells (iPSCs) offer the
      unique possibility for directed differentiation into mature podocytes. The
      current differentiation protocol to generate iPSC-derived podocyte-like cells
      provides a robust and reproducible method to obtain podocyte-like cells after 10
      days that can be employed in in vitro research and biomedical engineering.
      Previous published protocols were improved by testing varying differentiation
      media, growth factors, seeding densities, and time course conditions.
      Modifications were made to optimize and simplify the one-step differentiation
      procedure. In contrast to earlier protocols, adherent cells for differentiation
      were used, the use of fetal bovine serum (FBS) was reduced to a minimum, and thus
      beta-mercaptoethanol could be omitted. The plating densities of iPSC stocks as
      well as the seeding densities for differentiation cultures turned out to be a
      crucial parameter for differentiation results. Conditionally immortalized human
      podocytes served as reference controls. iPSC-derived podocyte-like cells showed a
      typical podocyte-specific morphology and distinct expression of podocyte markers
      synaptopodin, podocin, nephrin and WT-1 after 10 days of differentiation as
      assessed by immunofluorescence staining or Western blot analysis. qPCR results
      showed a downregulation of pluripotency markers Oct4 and Sox-2 and a 9-fold
      upregulation of the podocyte marker synaptopodin during the time course of
      differentiation. Cultured podocytes exhibited endocytotic uptake of albumin. In
      toxicological assays, matured podocytes clearly responded to doxorubicin
      (AdriamycinTM) with morphological alterations and a reduction in cell viability
      after 48 h of incubation.

PMID- 30222769
TI  - One-legged stance sway of older adults with and without falls.
AB  - Postural instability is a common problem among older people, and it is associated
      with mobility impairments, activity limitation and fear of falling. The
      evaluation of postural control can contribute to the early detection of balance
      deficits and help health professionals to manage this problem to prevent falls in
      older adults. The aim of this study was to identify center of pressure cut-offs
      to differentiate between older adults with and without falls in the past 12
      months. The participants were 170 older adults (mean age 67 years, 50 fallers and
      120 non-fallers). Center of pressure area and sway velocity in the anterior
      posterior and medio-lateral directions were assessed using a force platform
      during three 30s one-legged stance trials with eyes open. The mean across trials
      was used for analysis. The time-limit (how long the participant was able to stay
      in one-legged stance, up to 30s) was also assessed. Fallers had poorer postural
      control than non-fallers (effect size >= 0.52, P <0.05). The cut-offs identified
      were 10.3 cm2 for Center of pressure area, 2.9 cm/s for velocity in the anterior
      posterior, and 3.4 cm/s for medio-lateral velocity. The force platform parameters
      obtained an area under the curve of 0.72, with sensitivity of 78% and specificity
      of 68%. There were no significant differences between non-fallers and fallers for
      time-limit variable (17 seconds vs. 18 seconds). Force platform parameters during
      one-legged stance were associated with history of falls in older adults. The cut
      offs obtained acceptable area under curve, sensitivity and specificity, with
      center of pressure area presenting the best performance to differentiate between
      fallers and non-fallers.

PMID- 30222768
TI  - Cost-effectiveness of a combination strategy to enhance the HIV care continuum in
      Swaziland: Link4Health.
AB  - INTRODUCTION: Link4Health, a cluster-RCT, demonstrated the effectiveness of a
      combination strategy targeting barriers at various HIV continuum steps on linkage
      to and retention in care; showing effectiveness in achieving linkage to HIV care
      within 1 month plus retention in care at 12 months after HIV testing for people
      living with HIV (RR 1.48, 95% CI 1.19-1.96, p = 0.002). In addition to standard
      of care, Link4Health included: 1) Point-of-care CD4+ count testing; 2)
      Accelerated ART initiation; 3) Mobile phone appointment reminders; 4) Care and
      prevention package including commodities and informational materials; and 5) Non
      cash financial incentive. Our objective was to evaluate the cost-effectiveness of
      a scale-up of the Link4Health strategy in Swaziland. METHODS AND FINDINGS: We
      incorporated the effects and costs of the Link4Health strategy into a computer
      simulation of the HIV epidemic in Swaziland, comparing a scenario where the
      strategy was scaled up to a scenario with no implementation. The simulation
      combined a deterministic compartmental model of HIV transmission with a
      stochastic microsimulation of HIV progression calibrated to Swaziland
      epidemiological data. It incorporated downstream health costs potentially saved
      and infections potentially prevented by improved linkage and treatment adherence.
      We assessed the incremental cost-effectiveness ratio of Link4Health compared to
      standard care from a health sector perspective reported in US$2015, a time
      horizon of 20 years, and a discount rate of 3% in accordance with WHO
      guidelines.[1] Our results suggest that scale-up of the Link4Health strategy
      would reduce new HIV infections over 20 years by 11,059 infections, a 7%
      reduction from the projected 169,019 cases and prevent 5,313 deaths, an 11%
      reduction from the projected 49,582 deaths. Link4Health resulted in an
      incremental cost per infection prevented of $13,310 and an incremental cost per
      QALY gained of $3,560/QALY from the health sector perspective. CONCLUSIONS: Using
      a threshold of <3 x per capita GDP, the Link4Health strategy is likely to be a
      cost-effective strategy for responding to the HIV epidemic in Swaziland.

PMID- 30222770
TI  - Satellite cells delivered in their niche efficiently generate functional myotubes
      in three-dimensional cell culture.
AB  - Biophysical/biochemical cues from the environment contribute to regulation of the
      regenerative capacity of resident skeletal muscle stem cells called satellites
      cells. This can be observed in vitro, where muscle cell behaviour is influenced
      by the particular culture substrates and whether culture is performed in a 2D or
      3D environment, with changes including morphology, nuclear shape and cytoskeletal
      organization. To create a 3D skeletal muscle model we compared collagen I, Fibrin
      or PEG-Fibrinogen with different sources of murine and human myogenic cells. To
      generate tension in the 3D scaffold, biomaterials were polymerised between two
      flexible silicone posts to mimic tendons. This 3D culture system has multiple
      advantages including being simple, fast to set up and inexpensive, so providing
      an accessible tool to investigate myogenesis in a 3D environment. Immortalised
      human and murine myoblast lines, and primary murine satellite cells showed
      varying degrees of myogenic differentiation when cultured in these biomaterials,
      with C2 myoblasts in particular forming large multinucleated myotubes in collagen
      I or Fibrin. However, murine satellite cells retained in their niche on a muscle
      fibre and embedded in 3D collagen I or Fibrin gels generated aligned,
      multinucleated and contractile myotubes.

PMID- 30222771
TI  - Longitudinal transcriptomic characterization of the immune response to acute
      hepatitis C virus infection in patients with spontaneous viral clearance.
AB  - Most individuals exposed to hepatitis C virus (HCV) become persistently infected
      while a minority spontaneously eliminate the virus. Although early immune events
      influence infection outcome, the cellular composition, molecular effectors, and
      timeframe of the host response active shortly after viral exposure remain
      incompletely understood. Employing specimens collected from people who inject
      drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq and blood
      transcriptome module (BTM) analysis to characterize immune function in peripheral
      blood mononuclear cells (PBMC) before, during, and after acute HCV infection
      resulting in spontaneous resolution. Our results provide a detailed description
      of innate immune programs active in peripheral blood during acute HCV infection,
      which include prominent type I interferon and inflammatory signatures. Innate
      immune gene expression rapidly returns to pre-infection levels upon viral
      clearance. Comparative analyses using peripheral blood gene expression profiles
      from other viral and vaccine studies demonstrate similarities in the immune
      responses to acute HCV and flaviviruses. Of note, both acute dengue virus (DENV)
      infection and acute HCV infection elicit similar innate antiviral signatures.
      However, while transient in DENV infection, this signature was sustained for many
      weeks in the response to HCV. These results represent the first longitudinal
      transcriptomic characterization of human immune function in PBMC during acute HCV
      infection and identify several dynamically regulated features of the complex
      response to natural HCV exposure.

PMID- 30222772
TI  - Lower limb sagittal kinematic and kinetic modeling of very slow walking for gait
      trajectory scaling.
AB  - Lower extremity powered exoskeletons (LEPE) are an emerging technology that
      assists people with lower-limb paralysis. LEPE for people with complete spinal
      cord injury walk at very slow speeds, below 0.5m/s. For the able-bodied
      population, very slow walking uses different neuromuscular, locomotor, postural,
      and dynamic balance control. Speed dependent kinetic and kinematic regression
      equations in the literature could be used for very slow walking LEPE trajectory
      scaling; however, kinematic and kinetic information at walking speeds below 0.5
      m/s is lacking. Scaling LEPE trajectories using current reference equations may
      be inaccurate because these equations were produced from faster than real-world
      LEPE walking speeds. An improved understanding of how able-bodied people
      biomechanically adapt to very slow walking will provide LEPE developers with more
      accurate models to predict and scale LEPE gait trajectories. Full body motion
      capture data were collected from 30 healthy adults while walking on an
      instrumented self-paced treadmill, within a CAREN-Extended virtual reality
      environment. Kinematic and kinetic data were collected for 0.2 m/s-0.8 m/s, and
      self-selected walking speed. Thirty-three common sagittal kinematic and kinetic
      gait parameters were identified from motion capture data and inverse dynamics.
      Gait parameter relationships to walking speed, cadence, and stride length were
      determined with linear and quadratic (second and third order) regression. For
      parameters with a non-linear relationship with speed, cadence, or stride-length,
      linear regressions were used to determine if a consistent inflection occurred for
      faster and slower walking speeds. Group mean equations were applied to each
      participant's data to determine the best performing equations for calculating
      important peak sagittal kinematic and kinetic gait parameters. Quadratic models
      based on walking speed had the strongest correlations with sagittal kinematic and
      kinetic gait parameters, with kinetic parameters having the better results. The
      lack of a consistent inflection point indicated that the kinematic and kinetic
      gait strategies did not change at very slow gait speeds. This research showed
      stronger associations with speed and gait parameters then previous studies, and
      provided more accurate regression equations for gait parameters at very slow
      walking speeds that can be used for LEPE joint trajectory development.

PMID- 30222774
TI  - Correction: The changing epidemiological pattern of Dengue in Swat, Khyber
      Pakhtunkhwa.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0195706.].

PMID- 30222773
TI  - Highly multiplexed genome engineering using CRISPR/Cas9 gRNA arrays.
AB  - The CRISPR/Cas9 system is an RNA guided nuclease system that evolved as a
      mechanism of adaptive immunity in bacteria. This system has been adopted for
      numerous genome engineering applications in research and recently, therapeutics.
      The CRISPR/Cas9 system has been largely implemented by delivery of Cas9 as
      protein, RNA, or plasmid along with a chimeric crRNA-tracrRNA guide RNA (gRNA)
      under the expression of a pol III promoter, such as U6. Using this approach,
      multiplex genome engineering has been achieved by delivering several U6-gRNA
      plasmids targeting multiple loci. However, this approach is limited due to the
      efficiently of delivering multiple plasmids to a single cell at one time. To
      augment the capability and accessibility of multiplexed genome engineering, we
      developed an efficient golden gate based method to assemble gRNAs linked by
      optimal Csy4 ribonuclease sequences to deliver up to 10 gRNAs as a single gRNA
      array transcript. Here we report the optimal expression of our guide RNA array
      under a strong pol II promoter. This system can be implemented alongside the
      myriad of CRISPR applications, allowing users to model complex biological
      processes requiring numerous gRNAs.

PMID- 30222776
TI  - Does California's Low Carbon Fuel Standards reduce carbon dioxide emissions?
AB  - The Low Carbon Fuel Standards (LCFS) represents a new policy approach designed to
      reduce carbon dioxide emissions by applying standards to all stages of motor fuel
      production. We use the synthetic control and difference-in-differences
      econometric methods, and Lasso machine learning to analyze the effect of the LCFS
      on emissions in California's transportation sector. The three different
      techniques provide robust evidence that the LCFS reduced carbon dioxide emissions
      in California's transportation sector by around 10%. Furthermore, our
      calculations show that improved air quality, due to the application of the LCFS,
      may have benefited California in the magnitude of hundreds of millions of dollars
      through an increase in worker's productivity.

PMID- 30222775
TI  - Double burden of malnutrition among children under 5 in poor areas of China.
AB  - OBJECTIVE: The aim of this study was to investigate the nutritional status and
      its risk factors among children under 5 years, with special focus on the
      coexistence of under and over nutrition in population level. METHODS: We enrolled
      6,570 children under 5 years among 26 counties in poor areas of China.
      Prevalences of malnutrition (stunting, underweight, wasting, overweight) were
      calculated. Overweight was evaluated using two indicators-weight for height Z
      score (WHZ) and body mass index for age Z score (BAZ), and results were compared.
      RESULTS: The total prevalence of malnutrition was 19.2%. The prevalence of
      stunting and overweight were as high as 8.4% and 8.8%, respectively. The BAZ
      estimated prevalence of overweight was 9.9%, which was higher than the WHZ
      estimated prevalence (p<0.001). Children older than 12 months age, within a
      minority group, with a caregiver of illiteracy/primary education level were
      significantly associated with stunting in multilevel regression models (p<0.05).
      Children younger than 24 months age and boys were significantly associated with
      overweight (p<0.05). CONCLUSIONS: Stunting and overweight were coexisted in
      surveyed areas. In conclusion, BAZ tended to overestimate the overweight
      prevalence compared with WHZ. While with the raising problem of childhood
      overweight, stunting should still be on the agenda for the poor areas in China.
      To improve children's nutritional status in poor areas of China, caregivers with
      children at high risk of malnutrition should be guided for healthy feeding
      practices.

PMID- 30222778
TI  - Evaluation on the tribological performance of ring/liner system under cylinder
      deactivation with consideration of cylinder liner deformation and oil supply.
AB  - In gasoline engines, CDA (cylinder deactivation) affects greatly the tribological
      performance of ring/liner system while reducing the emissions and improving the
      fuel economy. The analyses on the tribological performance of ring/liner system
      under the CDA mainly focus on the ideal circular cylinder liner and fixed fully
      flooded lubrication condition. In this study, a numerical investigation on the
      tribological performance of a compression ring-cylinder liner system is presented
      under the CDA with consideration of the cylinder liner deformation and the
      transition between the fully flooded and starved lubrication conditions. A mixed
      lubrication model coupled with oil transport model and JFO (Jacobson-Floberg
      Olsson) conservative cavitation algorithm is proposed to evaluate the frictional
      properties. Based on the model, the tribological performance is investigated
      under the standard operation condition and the CDA. Meanwhile, the influence of
      cylinder liner deformation and oil supply on the tribological performance is also
      evaluated. Results show that the tribological performance of the compression ring
      cylinder liner system is greatly changed when the CDA is adopted. In particular,
      under the CDA, the overall power loss and FMEP (friction mean effective pressure)
      value are increased about 27.29% and 53.51%. The study also demonstrates the
      necessity to consider the cylinder liner deformation and oil supply in the
      simulation of compression ring-cylinder liner system under the CDA.

PMID- 30222777
TI  - Refining muscle geometry and wrapping in the TLEM 2 model for improved hip
      contact force prediction.
AB  - Musculoskeletal models represent a powerful tool to gain knowledge on the
      internal forces acting at the joint level in a non-invasive way. However, these
      models can present some errors associated with the level of detail in their
      geometrical representation. For this reason, a thorough validation is necessary
      to prove the reliability of their predictions. This study documents the
      development of a generic musculoskeletal model and proposes a working logic and
      simulation techniques for identifying specific model features in need of
      refinement; as well as providing a quantitative validation for the prediction of
      hip contact forces (HCF). The model, implemented in the AnyBody Modeling System
      and based on the cadaveric dataset TLEM 2.0, was scaled to match the
      anthropometry of a patient fitted with an instrumented hip implant and to
      reproduce gait kinematics based on motion capture data. The relative contribution
      of individual muscle elements to the HCF and joint moments was analyzed to
      identify critical geometries, which were then compared to muscle magnetic
      resonance imaging (MRI) scans and, in case of inconsistencies, were modified to
      better match the volumetric scans. The predicted HCF showed good agreement with
      the overall trend and timing of the measured HCF from the instrumented
      prosthesis. The average root mean square error (RMSE), calculated for the total
      HCF was found to be 0.298*BW. Refining the geometries of the muscles thus
      identified reduced RMSE on HCF magnitudes by 17% (from 0.359*BW to 0.298*BW) over
      the whole gait cycle. The detailed study of individual muscle contributions to
      the HCF succeeded in identifying muscles with incorrect anatomy, which would have
      been difficult to intuitively identify otherwise. Despite a certain residual over
      prediction of the final hip contact forces in the stance phase, a satisfactory
      level of geometrical accuracy of muscle paths has been achieved with the
      refinement of this model.

PMID- 30222780
TI  - Clinical molecular testing for ASXL1 c.1934dupG p.Gly646fs mutation in
      hematologic neoplasms in the NGS era.
AB  - ASXL1 (additional sex combs like 1) is a gene that is mutated in a number of
      hematological neoplasms. The most common genetic alteration is c.1934dupG
      p.Gly646fs. Previous publications have shown that ASXL1 mutations have a negative
      prognostic impact in patients with MDS and AML, however, controversy exists
      regarding the molecular testing of ASXL1 c.1934dupG as polymerase splippage over
      the adjacent homopolymer could lead to a false-positive result. Here, we report
      the first study to systematically test different targeted next generation
      sequencing (NGS) approaches for this mutation in patients with hematologic
      neoplasms. In addition, we investigated the impact of proofreading capabilities
      of different DNA polymerases on ASXL1 c.1934dupG somatic mutation using
      conventional Sanger sequencing, another common method for ASXL1 genotyping. Our
      results confirm that ASXL1 c.1934dupG can be detected as a technical artifact,
      which can be overcome by the use of appropriate enzymes and library preparation
      methods. A systematic study of serial samples from 30 patients show that ASXL1
      c.1934dupG is a somatic mutation in haematological neoplasms including MDS, AML,
      MPN and MDS/MPN and often is associated with somatic mutations of TET2, EZH2,
      IDH2, RUNX1, NRAS and DNMT3A. The pattern of clonal evolution suggests that this
      ASXL1 mutation might be an early mutational event that occurs in the principal
      clonal population and can serve as a clonal marker for persistent/relapsing
      disease.

PMID- 30222779
TI  - Disrupted structure and aberrant function of CHIP mediates the loss of motor and
      cognitive function in preclinical models of SCAR16.
AB  - CHIP (carboxyl terminus of heat shock 70-interacting protein) has long been
      recognized as an active member of the cellular protein quality control system
      given the ability of CHIP to function as both a co-chaperone and ubiquitin
      ligase. We discovered a genetic disease, now known as spinocerebellar autosomal
      recessive 16 (SCAR16), resulting from a coding mutation that caused a loss of
      CHIP ubiquitin ligase function. The initial mutation describing SCAR16 was a
      missense mutation in the ubiquitin ligase domain of CHIP (p.T246M). Using
      multiple biophysical and cellular approaches, we demonstrated that T246M mutation
      results in structural disorganization and misfolding of the CHIP U-box domain,
      promoting oligomerization, and increased proteasome-dependent turnover. CHIP
      T246M has no ligase activity, but maintains interactions with chaperones and
      chaperone-related functions. To establish preclinical models of SCAR16, we
      engineered T246M at the endogenous locus in both mice and rats. Animals
      homozygous for T246M had both cognitive and motor cerebellar dysfunction distinct
      from those observed in the CHIP null animal model, as well as deficits in
      learning and memory, reflective of the cognitive deficits reported in SCAR16
      patients. We conclude that the T246M mutation is not equivalent to the total loss
      of CHIP, supporting the concept that disease-causing CHIP mutations have
      different biophysical and functional repercussions on CHIP function that may
      directly correlate to the spectrum of clinical phenotypes observed in SCAR16
      patients. Our findings both further expand our basic understanding of CHIP
      biology and provide meaningful mechanistic insight underlying the molecular
      drivers of SCAR16 disease pathology, which may be used to inform the development
      of novel therapeutics for this devastating disease.

PMID- 30222781
TI  - Portal venous velocity affects liver regeneration after right lobe living donor
      hepatectomy.
AB  - OBJECTIVES: We investigated whether chronological changes in portal flow and
      clinical factors play a role in the liver regeneration (LR) process after right
      donor-hepatectomy. MATERIALS AND METHODS: Participants in this prospective study
      comprised 58 donors who underwent right donor-hepatectomy during the period
      February 2014 to February 2015 at a single medical institution. LR was estimated
      using two equations: remnant left liver (RLL) growth (%) and liver volumetric
      recovery (LVR) (%). Donors were classified into an excellent regeneration (ER)
      group or a moderate regeneration (MR) group based on how their LR on
      postoperative day 7 compared to the median value. RESULTS: Multivariate analysis
      revealed that low residual liver volume (OR = .569, 95% CI: .367- .882) and high
      portal venous velocity in the immediate postoperative period (OR = 1.220, 95% CI:
      1.001-1.488) were significant predictors of LR using the RLL growth equation;
      high portal venous velocity in the immediate postoperative period (OR = 1.325,
      95% CI: 1.081-1.622) was a significant predictor of LR using the LVR equation.
      Based on the two equations, long-term LR was significantly greater in the ER
      group than in the MR group (p < .001). CONCLUSION: Portal venous velocity in the
      immediate postoperative period was an important factor in LR. The critical time
      for short-term LR is postoperative day 7; it is associated with long-term LR in
      donor-hepatectomy.

PMID- 30222782
TI  - Correction: The Zinc-Schiff Base-Novicidin Complex as a Potential Prostate Cancer
      Therapy.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0163983.].

PMID- 30222783
TI  - Correction: Chemoenzymatic synthesis of sialylated lactuloses and their
      inhibitory effects on Staphylococcus aureus.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0199334.].

PMID- 30222784
TI  - Correction: Psychometric evaluation of the Chinese version of the fear of
      intimacy with helping professionals scale.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0196774.].

PMID- 30222785
TI  - Bone trait ranking in the population is not established during antenatal growth
      but is robustly established in the first postnatal year.
AB  - Efforts to understand the pathophysiology of bone fragility must focus on bone
      traits during growth. We hypothesized that variance in individual trait ranking
      in the population distribution is established by genetic factors and is reflected
      in foetal trait ranking in early pregnancy, but intrauterine factors modify trait
      ranking in late pregnancy, followed by the reinstating of this ranking during the
      first postnatal year. Thus, relations with paternal factors are present in early
      pregnancy but are then lost and subsequently reinstated postnatal. We recruited
      399 healthy pregnant women aged 20-42 years from The Mercy Hospital for Woman in
      Melbourne, Australia. Foetal femur length (FL) and knee-heel length (KHL) were
      measured by ultrasound during gestation, and FL, KHL, body length and weight were
      measured in neonates, infants, and parents. The z-scores were calculated using
      Royston models. Pearson correlation was used to assess tracking and linear mixed
      models to test the associations. Correlations between FL and KHL z-scores of the
      same trait at 20 and 30 weeks gestation, at birth, and at 12 and 24 months of age
      (r = 0.1-0.3) and of body length and weight at birth, and 6, 12 and 24 months (r
      = 0.3-0.5) became more robust after 6-12 months (r = 0.4-0.8). FL and KHL z
      scores at 20 weeks gestation accounted for 4-5% of total variance, while FL, KHL,
      body length and weight z-scores at birth accounted for 13-26% of total variance
      in the same traits at 24 months. Maternal FL and KHL were associated with foetal
      FL and KHL at 20 and 30 weeks, but there were no such associations for paternal
      FL and KHL with foetal traits during gestation. Both maternal and paternal traits
      were associated with infant traits. Tracking in traits is not established
      antenatal but is robustly established at 6-12 months of age.

PMID- 30222788
TI  - Comparative Efficacy of Intravenous With Intra-articular Versus Intravenous Only
      Administration of Tranexamic Acid to Reduce Blood Loss in Knee Arthroplasty.
AB  - The objective of this study was to ascertain whether combined intravenous (IV)
      and intra-articular (IA) administration of tranexamic acid (TXA) is beneficial
      for reducing blood loss and the prevalence of deep venous thrombosis (DVT) in
      primary simultaneous bilateral total knee arthroplasty compared with IV only
      administration of TXA. One hundred fifty-four patients received a combined IV and
      IA injection of TXA in 1 knee and an IV only injection of TXA in the other.
      Transfusion rates and volumes and the amount of blood loss were recorded at 8
      hours, 24 hours, and 48 hours. In addition, the authors ascertained whether the
      prevalence of DVT was higher in the patients with combined IV and IA
      administration of TXA than in the patients with IV only administration of TXA.
      Overall total blood loss was not significantly different (299.6 mL vs 280.1 mL,
      P=.22) between the 2 groups. The prevalence of DVT was 11% (17 knees) in the
      combined IV and IA group and 14% (22 knees) in the IV only group. This difference
      was not significant (P=.25). Combined IV and IA administration of TXA in
      bilateral total knee arthroplasty has no additional benefit in reducing total
      blood loss when compared with IV only administration. The prevalence of DVT was
      low and not significantly different between the 2 groups. Furthermore, no
      pulmonary embolism was found in either group. [Orthopedics. 2018; 41(6):e827
      e830.].

PMID- 30222787
TI  - Superoxide dismutase activity is significantly lower in end-stage osteoarthritic
      cartilage than non-osteoarthritic cartilage.
AB  - Recent studies have shown that superoxide dismutase 1 (SOD1), SOD2, and SOD3 are
      significantly decreased in human osteoarthritic cartilage. SOD activity is a
      marker that can be used to comprehensively evaluate the enzymatic capacities of
      SOD1, SOD2, and SOD3; however, the trend of SOD activity in end-stage
      osteoarthritic tissues remains unknown. In the present study, we found that SOD
      activity in end-stage osteoarthritic synovium of the knee was significantly lower
      than that in control synovium without the influence of age. The SOD activity was
      significantly lower in the end-stage knee osteoarthritic cartilage than in the
      control, but a weak negative correlation was observed between aging and SOD
      activity. However, SOD activity in end-stage hip osteoarthritic cartilage was
      significantly lower than that in control cartilage without the influence of
      aging. The relationship between osteoarthritis and SOD activity was stronger than
      the relationship between aging and SOD activity. These results indicate that
      direct regulation of SOD activity in joint tissues may lead to suppression of
      osteoarthritis progression.

PMID- 30222786
TI  - MAPK and GSK3/beta-TRCP-mediated degradation of the maternal Ets domain
      transcriptional repressor Yan/Tel controls the spatial expression of nodal in the
      sea urchin embryo.
AB  - In the sea urchin embryo, specification of the dorsal-ventral axis critically
      relies on the spatially restricted expression of nodal in the presumptive ventral
      ectoderm. The ventral restriction of nodal expression requires the activity of
      the maternal TGF-beta ligand Panda but the mechanism by which Panda restricts
      nodal expression is unknown. Similarly, what initiates expression of nodal in the
      ectoderm and what are the mechanisms that link patterning along the primary and
      secondary axes is not well understood. We report that in Paracentrotus lividus,
      the activity of the maternally expressed ETS-domain transcription factor Yan/Tel
      is essential for the spatial restriction of nodal. Inhibiting translation of
      maternal yan/tel mRNA disrupted dorsal-ventral patterning in all germ layers by
      causing a massive ectopic expression of nodal starting from cleavage stages,
      mimicking the phenotype caused by inactivation of the maternal Nodal antagonist
      Panda. We show that like in the fly or in vertebrates, the activity of sea urchin
      Yan/Tel is regulated by phosphorylation by MAP kinases. However, unlike in the
      fly or in vertebrates, phosphorylation by GSK3 plays a central role in the
      regulation Yan/Tel stability in the sea urchin. We show that GSK3 phosphorylates
      Yan/Tel in vitro at two different sites including a beta-TRCP ubiquitin ligase
      degradation motif and a C-terminal Ser/Thr rich cluster and that phosphorylation
      of Yan/Tel by GSK3 triggers its degradation by a beta-TRCP/proteasome pathway.
      Finally, we show that, Yan is epistatic to Panda and that the activity of Yan/Tel
      is required downstream of Panda to restrict nodal expression. Our results
      identify Yan/Tel as a central regulator of the spatial expression of nodal in
      Paracentrotus lividus and uncover a key interaction between the gene regulatory
      networks responsible for patterning the embryo along the dorsal-ventral and
      animal-vegetal axes.

PMID- 30222789
TI  - The Shoulder Self-Administered Motion Evaluation Has Excellent Patient
      Reliability and Reproducibility on Both Physician and Repeat Follow-up Testing.
AB  - Long-term clinical evaluation is becoming more important, yet difficulties exist
      because there are substantial patient costs for extended follow-up. The goal of
      this study was to validate whether a new shoulder motion evaluation is
      reproducible and reliable with physician examination. Consecutive patients were
      administered a shoulder motion assessment during their clinic visit. Patients
      completed the same evaluation 2 weeks after their visit to determine test-retest
      reliability. Exact and approximate (within 20 degrees  or 4 spinal levels)
      agreements between patient and physician measurements were calculated. A total of
      112 patients (224 shoulders) with an average age of 56.7 years were evaluated.
      The most common diagnoses were osteoarthritis (33.0%) and rotator cuff tear
      (32.1%). All motion questions had greater than 50% exact patient-physician
      agreement and greater than 70% approximate agreement. When agreement was off,
      patients more often underestimated their motion. There was substantial clinician
      patient agreement for all questions and almost perfect agreement for forward
      elevation (intraclass correlation coefficient, 0.78) and internal rotation
      (intraclass correlation coefficient, 0.77). On test-retest reliability testing,
      patient-patient agreement was substantial for external rotation at the side
      (intraclass correlation coefficient, 0.71). There was near perfect agreement for
      internal rotation (intraclass correlation coefficient, 0.83) and abduction
      (intraclass correlation coefficient, 0.81) testing. This shoulder assessment tool
      had both good agreement to physician examination and substantial agreement on
      correlation testing. There was substantial agreement between follow-up visits,
      suggesting excellent reproducibility. This motion assessment shows effectiveness
      with most shoulder pathologies. It is recommended as a good screening tool for
      both clinical and research purposes requiring long-term follow-up in which in
      person clinical examinations may be costly and time consuming. [Orthopedics.
      2018; 41(6):e820-e826.].

PMID- 30222790
TI  - The Correlation Between PROMIS Pain Interference and VAS Pain in Ambulatory
      Orthopedic Patients.
AB  - The purpose of this study was to investigate the correlation of Patient-Reported
      Outcomes Measurement Information System (PROMIS) Pain Interference (PI) score
      with traditionally collected visual analog scale (VAS) scores and to determine
      the influence of patient demographics on PROMIS PI and VAS scores. Patient
      demographics were collected, and PROMIS PI, PROMIS Physical Function (PF), and
      VAS questionnaires were distributed to 215 patients in orthopedic ambulatory
      clinics. The primary outcome was correlation between PROMIS PI and VAS
      questionnaires. The statistical method of seemingly unrelated regressions was
      used to identify significant predictors and strengths of correlation between
      PROMIS PI and conventional forms. The PROMIS PI score was highly correlated to
      conventional pain and functional scores, with each standard deviation increase in
      PROMIS PI score predicting a 16-point increase for pain-related VAS scores
      (current pain, pain at rest, pain during activity, pain at night), an 18-point
      decrease in satisfaction of function score, and a 6-point decrease in general
      health score. Each standard deviation increase in PROMIS PF score for black
      patients predicted a reduction of 11 points for current pain, 10 points for pain
      at rest, 10 points for pain during activity, and 12 points for pain at night
      scores. The PROMIS PI score consistently predicts changes in VAS pain scores and
      can be considered a useful, standardized tool for measuring pain for clinical and
      research purposes. [Orthopedics. 2018; 41(6):e813-e819.].

PMID- 30222791
TI  - Biomechanical Properties of the Lateral Patellofemoral Ligament: A Cadaveric
      Analysis.
AB  - Medial instability of the patellofemoral joint is a rare but known phenomenon; it
      may result from an incompetent lateral patellofemoral ligament (LPFL). However,
      biomechanical details of the ligament have not been the subject of scrutiny. The
      purpose of this study was to describe the biomechanical properties of the LPFL.
      Ten fresh-frozen human cadaveric knees were dissected to identify the LPFL. The
      ligament was harvested with a bone plug from the patella and the femoral surface
      and underwent axial loading to failure. Load to failure and location of failure
      were recorded. Regression analysis was performed to determine which anatomic
      variables (midsubstance width, femoral insertion width, patellar insertion width,
      or percent patellar articular surface of insertion) significantly influenced load
      to failure. Nine of the 10 specimens failed at the midsubstance of the ligament.
      The mean load to failure was 90+/-67 N. Logistical regression showed that
      midsubstance width was most correlated with load to failure, which approached but
      did not reach significance (P=.09). Studies are warranted to investigate the
      clinical consequences of medial patellar instability and the best repair or
      reconstruction techniques available. [Orthopedics. 2018; 41(2):e797-e801.].

PMID- 30222792
TI  - Delving Deeper Into Informed Consent: Legal and Ethical Dilemmas of Emergency
      Consent, Surrogate Consent, and Intraoperative Consultation.
AB  - Informed consent is gaining an ever-important place in modern medicine. The
      practice of patient-centered medicine along with evidence-based medicine requires
      a balance between the patient's wishes and the physician's oath to do no harm.
      Surrogate consent, emergency consent, and intraoperative consultation are 3
      situations prone to legal and ethical dilemmas in the fulfillment of informed
      consent. By examining the proposed models and legal precedents that address the
      challenges in informed consent, discussion of these dilemmas in the context of
      both law and bioethics may provide a better understanding of how to resolve them.
      [Orthopedics. 2018; 41(6):e741-e746.].

PMID- 30222793
TI  - Short-Segment Fixation With Percutaneous Pedicle Screws in the Treatment of
      Unstable Thoracolumbar Vertebral Body Fractures.
AB  - Clinical care of patients with unstable thoracolumbar vertebral body fractures
      may be challenging, especially in the setting of polytrauma patients who require
      other acute intervention. Compared with the traditional open approach,
      percutaneous short-segment fixation constructs place less surgical burden on
      patients regarding operative time and blood loss. Between 2008 and 2012, 32
      patients with a mean age of 49 years (range, 19-80 years) underwent percutaneous
      short-segment fixation at the authors' institution and had a minimum of 6 months
      of complete clinical and radiographic follow-up. Load-sharing classification
      scores were determined. Outcomes evaluated included anterior body height,
      posterior body height, local kyphosis, regional kyphosis, thoracolumbar
      junctional kyphosis, mean operative time, and total blood loss. Standard binomial
      and categorical comparative analyses were performed. All load-sharing
      classification scores were 7 or less, and 11 of the 32 patients were polytrauma
      patients requiring surgery. No difference was seen between preoperative and late
      measurements of anterior body height, posterior body height, local kyphosis,
      regional kyphosis, or thoracolumbar junctional kyphosis. There were no
      complications, revisions, or anterior corpectomies. Only 2 patients (6%)
      underwent elective removal of hardware at 1 year. Mean operative time was 43
      minutes (range, 33-56 minutes), and mean estimated blood loss was less than 50
      mL. Percutaneous short-segment fixation prevented loss of vertebral body height
      and progression of kyphosis in the treatment of unstable thoracolumbar fractures
      with load-sharing classification scores of 7 or less. This study shows that these
      fractures with a load-sharing classification score of 6 and 7 may be stabilized
      using fewer screws than traditional methods in some patients and allow polytrauma
      patients to undergo other acute treatment. [Orthopedics. 2018; 41(6):e802-e806.].

PMID- 30222794
TI  - Prophylactic Celecoxib Administration Is Associated With Decreased Incidence and
      Severity of Heterotopic Ossification After Hip Resurfacing by Direct Lateral
      Approach in Male Patients.
AB  - Heterotopic ossification is a potential complication that may have a particularly
      higher association with hip resurfacing. The 2 current mainstays for heterotopic
      ossification treatment and prophylaxis are administration of nonsteroidal anti
      inflammatory drugs and radiotherapy. Recent studies have determined that
      celecoxib is effective in heterotopic ossification prophylaxis after total hip
      arthroplasty. However, considering the reportedly higher incidence and severity
      of heterotopic ossification in these patients, relatively few studies have
      evaluated its role in hip resurfacing. Therefore, the authors assessed the
      incidence, severity, and risk factors of heterotopic ossification in patients who
      had hip resurfacing and did or did not receive celecoxib. Of the 198 patients, 83
      received celecoxib and 115 did not. Radiographs were examined to grade
      heterotopic ossification using the Brooker classification system. The rate of
      heterotopic ossification differed between patients who did and patients who did
      not receive celecoxib prophylaxis (25% vs 65%, P<.001). Celecoxib was an
      independent predictor of decreased heterotopic ossification (odds ratio, 0.16;
      95% confidence interval, 0.08-0.35). Celecoxib administration is associated with
      decreased incidence and severity of heterotopic ossification after hip
      resurfacing performed using the direct lateral approach in male patients.
      [Orthopedics. 2018; 41(6):e807-e812.].

PMID- 30222795
TI  - Outcome of 3.5-mm Anatomical Locking Plates for the Treatment of Proximal Tibia
      Fractures Involving the Meta-Diaphyseal Junction.
AB  - The clinical and radiological outcomes of proximal tibia fractures involving the
      meta-diaphyseal junction treated with unilateral 3.5-mm locking precontoured
      anatomical plates are reported. Thirty-nine patients (41 proximal tibia
      fractures) who had proximal tibia fractures with complete meta-diaphyseal
      dissociation were enrolled in the study. For all patients, immediate
      postoperative and final follow-up simple radiographs were evaluated to determine
      the quality of the reduction by assessing coronal and sagittal alignment. In
      cases of intra-articular involvement, articular reduction quality and condylar
      width were additionally assessed. Clinical outcomes were assessed by knee range
      of motion and Lysholm knee score at final follow-up. Immediate postoperative
      radiographs showed satisfactory results: medial proximal tibial angle within 87
      degrees +/-5 degrees  in 87.8% (36 of 41), posterior tibia slope within 9 degrees
      +/-5 degrees  in 85.4% (35 of 41), less than 2-mm articular step or gap in 79.3%
      (23 of 29), and a condylar width difference within 5 mm compared with the femoral
      condyles in 93.1% (27 of 29). All reductions but 1 were found to have
      satisfactory maintenance of the initial reduction. At final follow-up, the mean
      knee range of motion and Lysholm knee score were 122.5 degrees  (range, 100
      degrees -135 degrees ) and 75.8 (range, 50-100), respectively. A single lateral
      3.5-mm plate fixation for proximal tibia fractures involving the meta-diaphyseal
      junction offers mechanically stable fixation with satisfactory clinical and
      radiological outcomes. [Orthopedics. 2018; 41(6):e777-e782.].

PMID- 30222796
TI  - Patients With Valgus Alignment and Patients With Varus Alignment Are Not Mere
      Opposites of Each Other Prior to Total Knee Arthroplasty.
AB  - Although it is common practice to assess alignment prior to total knee
      arthroplasty, preoperative knee alignment and its effect on patient-reported
      outcomes (PROs) postoperatively has not been well studied. The purpose of this
      retrospective study was to determine if there are differences in PROs between
      patients with valgus deformities and patients with varus deformities. Further,
      this study assessed the baseline differences between these 2 groups
      preoperatively. Patients were placed into either the valgus or the varus group.
      Data collected included age, sex, race, height, weight, body mass index, knee
      alignment, Kellgren-Lawrence grade, and 2 PRO measures. Patient-reported outcomes
      were assessed preoperatively and at 5 scheduled follow-up visits during the first
      year postoperatively. The authors found that a higher percentage of female
      patients had a valgus deformity (84.9%). The varus group tended to have a higher
      body mass index. Radiographs revealed differences in tibia and femur deformities.
      The overall deformity was less in patients with a valgus deformity than in
      patients with a varus deformity (mean, 6.6 degrees  [SD, 4.4 degrees ] vs 8.6
      degrees  [SD, 4.8 degrees ], P=.010). Preoperative Knee injury and Osteoarthritis
      Outcome Score symptoms were significantly worse in the valgus group (P=.033).
      After adjusting for the significant baseline differences, all patients reported
      improved PROs during the postoperative period (P<.0001). Preoperatively, patients
      with valgus deformities and patients with varus deformities do not appear to be
      mere opposites of one another. The groups differed by sex, Knee injury and
      Osteoarthritis Outcome Score symptoms, and tibia, fibula, and overall deformity.
      Postoperatively, there were no significant differences in PROs during and up to 1
      year. [Orthopedics. 2018; 41(6):e783-e788.].

PMID- 30222797
TI  - Preoperative Hypoalbuminemia Predicts Poor Short-term Outcomes for Hip Fracture
      Surgery.
AB  - Hip fractures are common in elderly patients, and which surgical modality to
      pursue is often debated. Malnutrition, which cannot be corrected preoperatively
      in this population, is often not considered. Therefore, the authors sought to
      investigate the association between hypoalbuminemia and postoperative outcomes
      based on surgical intervention. Patients undergoing arthroplasty
      (hemiarthroplasty or total hip arthroplasty), open reduction and internal
      fixation, and intramedullary nailing placement for treatment of hip fractures
      were identified in the American College of Surgeons National Surgical Quality
      Improvement Program database. Patients were stratified by preoperative albumin
      level, with less than 3.5 g/dL indicating hypoalbuminemia. Albumin's association
      with postoperative complications was evaluated with multivariate logistic
      regression controlling for patient age, body mass index, American Society of
      Anesthesiologists score, and functional independence. A total of 20,278 patients
      with hip fractures and available albumin levels were included. Multivariate
      analysis revealed hypoalbuminemia was predictive of readmission, reintubation,
      mortality, and length of stay for all surgeries performed. When analyzing across
      surgical modalities, unique complications were identified for patients with
      hypoalbuminemia undergoing open reduction and internal fixation/prosthetic
      replacement (reoperation, P<.001) and arthroplasty (any infection, P=.028)
      compared with other treatment options. Hypoalbuminemia can predict postoperative
      complications for patients with hip fractures and should be considered
      preoperatively to guide surgical decision making in equivocal cases where
      multiple modalities may be used based on fracture pattern. This study supports
      that, compared with other interventions, intramedullary nailing is associated
      with fewer postoperative complications in patients with hypoalbuminemia.
      [Orthopedics. 2018; 41(6):e789-e796.].

PMID- 30222798
TI  - Letter to the Editor: Efficacy of the Intravitreal Sustained-Release
      Dexamethasone Implant for DME Refractory to Anti-VEGF Therapy: Meta-Analysis and
      Clinical Implications.

PMID- 30222799
TI  - Spectral-Domain Optical Coherence Tomography Findings in Patients With Macropsia.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the retinal morphologic characteristics of
      patients with macropsia caused by epiretinal membrane (ERM) based on spectral
      domain optical coherence tomography (SD-OCT). PATIENTS AND METHODS: A cross
      sectional, non-interventional study was performed to compare the characteristics
      of retinal structures in eyes with ERM according to the presence or absence of
      macropsia. Twenty-six patients with ERM and macropsia were defined as the
      macropsia group and 26 age-matched patients with ERM without macropsia were the
      control group. All participants underwent a full ophthalmologic examination and
      SD-OCT examination. Macropsia was diagnosed and quantified using a double dot
      chart. The thickness of retinal layers, including the outer nuclear layer (ONL)
      and inner segment / outer segment / retinal pigment epithelium (IS/OS/RPE) at the
      central fovea, were measured by electronic calipers of the SD-OCT system. The
      interocular ratio of each parameter was calculated for each patient and compared
      between the two groups. The integrity of the external limiting membrane (ELM),
      IS/OS junction, and cone outer segment tips (COST) line were evaluated. RESULTS:
      The thickness of the IS/OS/RPE differed significantly between both eyes in the
      macropsia group (P < .001), whereas the control group was not significantly
      different (P = .161). The ONL in the diseased eye was significantly thicker in
      the macropsia group than in the control group (P = .020), whereas these two
      groups did not differ significantly in the thickness of ONL in the control eye (P
      = .860). More patients had a disrupted COST line in the macropsia group (P < .001
      for macropsia group, P = .252 for control group). No eye showed disrupted ELM and
      IS/OS junction, regardless of the presence of macropsia. CONCLUSIONS: Eyes with
      macropsia showed thicker foveal ONL, IS/OS/RPE, and more frequently disrupted
      COST lines. This may indicate that the contractile strength of ERM can lead to
      centralization of photoreceptor cells. [Ophthalmic Surg Lasers Imaging Retina.
      2018;49:656-663.].

PMID- 30222800
TI  - Macular and Peripapillary Choroidal Thickness in Patients With Keratoconus.
AB  - BACKGROUND AND OBJECTIVE: To investigate and compare macular and peripapillary
      choroidal thickness and profiles of patients with keratoconus and age-matched
      controls and correlate subfoveal choroidal thickness with keratoconus severity.
      PATIENTS AND METHODS: This was a prospective, observational, cross-sectional
      study comprising 45 keratoconus patients and 56 healthy controls. Choroidal
      thicknesses at the fovea and at 750-MUm intervals from the fovea to 1.5 mm in the
      nasal and temporal directions were measured by spectral-domain optical coherence
      tomography. Peripapillary choroidal thickness was measured at six segments along
      the circle scan. RESULTS: Mean age did not differ between the patients with
      keratoconus and controls (24.5 +/- 7.2 vs. 22.5 +/- 7.4 years, P = .170). Mean
      subfoveal choroidal thickness was higher in the keratoconus group (427.48 MUm +/-
      78.51 MUm) than in controls (351.03 MUm +/- 99.08 MUm; P < .001). Mean subfoveal
      choroidal thickness did not differ between mild and severe keratoconus (437.82 +/
      53.4 vs. 418.87 +/- 113.9 MUm; P = .660). In the macular area, choroidal
      thickness was lower at 1.5 mm nasal to the fovea (P < .0001) in both groups. The
      choroid was thinner at 0.75 mm temporal to the fovea than under the fovea in the
      keratoconus group (P < .001). The peripapillary choroid was thinner in the
      inferonasal and inferotemporal segments than in the other segments in both groups
      (P < .001). The peripapillary choroid was thinner in the inferonasal segment than
      in the inferotemporal segment in the keratoconus group (P = .018). CONCLUSION:
      Subfoveal choroidal thickening is observed in keratoconus eyes. The
      pathophysiological role of choroidal thickness variations should be considered in
      the natural history of keratoconus. [Ophthalmic Surg Lasers Imaging Retina.
      2018;49:664-673.].

PMID- 30222801
TI  - Peripheral Retinal Nonperfusion in Pediatric Patients With Morning Glory
      Syndrome.
AB  - BACKGROUND AND OBJECTIVE: To report the association of morning glory syndrome
      (MGS) with peripheral retinal nonperfusion in pediatric patients with MGS.
      PATIENTS AND METHODS: The authors retrospectively analyzed the records of
      pediatric patients with MGS using fundus fluorescein angiography. The peripheral
      retinal vascular architecture was recorded and graded according to the severity
      of peripheral retinal nonperfusion. RESULTS: Eighty-six eyes of 74 patients were
      enrolled. Seventy-three of 86 eyes (84.88%) had peripheral retinal nonperfusion,
      in which mild severity was found in 31 of 86 eyes (36.05%), moderate in 17 of 86
      eyes (19.77%), severe in 18 of 86 eyes (20.93%), and extreme in seven of 86 eyes
      (8.14%). Secondary complications of nonperfusion included leakage in six of 73
      eyes (8.22%), fibrovascular proliferation in two of 73 eyes (2.74%), and
      tractional retinal detachment in one of 73 eyes (1.34%). CONCLUSION: There is a
      high prevalence of peripheral retinal nonperfusion in pediatric MGS eyes, with
      secondary complications in some, suggesting that more attention should be paid to
      the peripheral retina in MGS. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:674
      679.].

PMID- 30222802
TI  - Secondary Ocular Hypertension and the Risk of Glaucoma Surgery After
      Dexamethasone Intravitreal Implant in Routine Clinical Practice.
AB  - BACKGROUND AND OBJECTIVES: To determine the rate of ocular hypertension (OHT)
      after dexamethasone intravitreal implant in routine clinical practice and
      identify patient characteristics associated with a risk for glaucoma surgery.
      PATIENTS AND METHODS: The charts of 260 eyes from 221 patients with diabetic
      macular edema, retinal vein occlusion, uveitis, and macular edema secondary to
      various causes treated with one or more dexamethasone implants were reviewed.
      Intraocular pressure (IOP), medications, and glaucoma interventions were
      collected before and after implantation. RESULTS: The mean baseline IOP was 14.3
      mm Hg +/- 3.6 mm Hg, and after receiving dexamethasone implant(s), 26.2% and 7.7%
      of patients had IOP greater than 25 mm Hg and 35 mm Hg, respectively. There was
      evidence (P < .001) of an association between preexisting glaucoma or glaucoma
      suspect status (103 eyes) and need for glaucoma surgery, and 4.62% (12 eyes)
      required glaucoma surgery. CONCLUSIONS: Secondary OHT induced by the
      dexamethasone implant can usually be controlled by medications, but the incidence
      of OHT requiring glaucoma surgery was high (4.62%) in our study relative to rates
      previously reported in the literature. All patients, especially those with
      preexisting glaucoma, should be advised of the possible need for glaucoma surgery
      prior to undergoing treatment with the dexamethasone implant. [Ophthalmic Surg
      Lasers Imaging Retina. 2018;49:680-685.].

PMID- 30222803
TI  - Post-Traumatic Giant Retinal Tear Without Posterior Vitreous Detachment: A Case
      Series.
AB  - BACKGROUND AND OBJECTIVE: To investigate the vitreal condition in retinal
      detachment (RD) related to giant retinal tears (GRT) after ocular blunt trauma.
      PATIENTS AND METHODS: Retrospective, observational study conducted at Azienda
      Ospedaliera Universitaria Careggi, Florence, Italy. The institutional review
      board and ethics committee approved the study. Records of 23 eyes of 23 patients
      affected by traumatic RD associated with a GRT were evaluated. A total of four
      eyes had RD related to blunt trauma, in which the authors performed 25-gauge
      vitrectomy and silicone oil was used as a endotamponade. RESULTS: Three out of
      four eyes did not display a posterior vitreous detachment at the B-scan, and this
      was confirmed during surgery. The three eyes had a mean visual acuity of 20/32 1
      month after silicone oil removal. CONCLUSIONS: Posterior vitreous detachment may
      not be present in RD associated with GRT after blunt trauma. This knowledge could
      result in modified intraoperative management to improve postoperative outcomes.
      [Ophthalmic Surg Lasers Imaging Retina. 2018;49:686-690.].

PMID- 30222804
TI  - Suprachoroidal Space Alterations Following Delivery of Triamcinolone Acetonide:
      Post-Hoc Analysis of the Phase 1/2 HULK Study of Patients With Diabetic Macular
      Edema.
AB  - BACKGROUND AND OBJECTIVE: To study anatomic changes in the suprachoroidal space
      (SCS) following suprachoroidal injection of CLS-TA, triamcinolone acetonide
      injectable suspension. PATIENTS AND METHODS: Eyes with diabetic macular edema
      receiving CLS-TA were imaged serially using anterior segment spectral-domain
      optical coherence tomography to examine the SCS. RESULTS: At the final imaging
      session, the SCS was not significantly different in study eyes (n = 14; 8.4 MUm)
      compared to fellow eyes (n = 10; 8.1 MUm; P = .698). Two eyes were imaged
      immediately before and 30 minutes after suprachoroidal injections; in these eyes,
      mean suprachoroidal width increased significantly following CLS-TA injection, 9.9
      MUm to 75.1 MUm (P < .001), and subsequently returned to 14.9 MUm 1 month after
      the final injection (P = .221). CONCLUSION: Suprachoroidal CLS-TA injection
      caused a measurable increase in the SCS, which returned to preinjection levels by
      1 month following injection with no apparent lasting impact on SCS anatomy.
      [Ophthalmic Surg Lasers Imaging Retina. 2018;49:692-697.].

PMID- 30222805
TI  - Visual Acuity Outcomes in Diabetic Macular Edema With Fluocinolone Acetonide 0.2
      MUg/Day Versus Ranibizumab Plus Deferred Laser (DRCR Protocol I).
AB  - BACKGROUND AND OBJECTIVE: Visual outcomes of the FAME study (0.2 MUg/day
      fluocinolone acetonide [FAc]) and Protocol I (0.5 mg ranibizumab plus deferred
      laser) were compared using the area under the curve (AUC) analysis method.
      PATIENTS AND METHODS: Best-corrected visual acuity (BCVA) data collected during a
      period of 3 years of follow-up for patients enrolled in FAME or Protocol I were
      used to calculate AUC of the change in BCVA over a time curve. RESULTS: In the
      overall population, there was a greater treatment effect for ranibizumab plus
      deferred laser compared with FAc. However, for subgroups of pseudophakic eyes,
      eyes with chronic diabetic macular edema (DME), and pseudophakic eyes with
      chronic DME, ranibizumab plus deferred laser and FAc were not found to be
      significantly different. The ranibizumab group received a median of 14 injections
      during a 36-month period compared with a mean of 1.3 injections in the FAc group.
      CONCLUSION: In pseudophakic and chronic DME subgroups, FAc was comparable to
      ranibizumab plus deferred laser with fewer injections. [Ophthalmic Surg Lasers
      Imaging Retina. 2018;49:698-706.].

PMID- 30222806
TI  - Subretinal Cysticercosis Extraction With Bimanual, 3-D, Heads-Up-Assisted Pars
      Plana Vitrectomy: Clinicopathological Correlation and Surgical Technique.
AB  - A 16-year-old male presented with blurred vision in the right eye after recent
      travel to Nicaragua. Funduscopic examination revealed subretinal cysticercosis
      superior to the optic nerve. The cyst was drained and excised using a bimanual,
      three-dimensional, heads-up-assisted pars plana vitrectomy without complications.
      Technical maneuvers for cyst extraction along with clinicopathological
      correlation are described. Postoperatively, the patient exhibits no signs of
      recurrence and has excellent vision. [Ophthalmic Surg Lasers Imaging Retina.
      2018;49:708-711.].

PMID- 30222807
TI  - 27-Gauge Via Pars Plana Vitrectomy With Autologous ILM Transplantation for Optic
      Pit Disc Maculopathy.
AB  - To report a case of a serous macular detachment associated with optic pit that
      did not improve after a previous vitrectomy with internal limiting membrane (ILM)
      peeling, peripapillary laser, and gas tamponade. The authors performed a lens
      sparing 27-gauge pars plana vitrectomy with autologous transplantation of ILM
      inside the optic nerve pit and gas tamponade. The subretinal fluid gradually
      resolved and visual acuity improved to 20/20 at the tenth month after surgery.
      The authors did not observe a recurrence of subretinal fluid during the 14 months
      of follow-up. Autologous transplantation of the ILM may be effective to repair
      recurring optic disc pit maculopathy. [Ophthalmic Surg Lasers Imaging Retina.
      2018;49:712-714.].

PMID- 30222808
TI  - Dedifferentiation of Retinal Pigment Epithelium in a Patient With Chronic Retinal
      Detachment.
AB  - A 34-year-old woman presented with vision loss in her right eye, which had
      persisted for approximately 12 months. Funduscopy showed horseshoe retinal tear
      at the 8-o'clock position and retinal detachment in inferior, nasal, and temporal
      quadrants, with a pigmented demarcation line in the right eye. Diffuse punctate
      accumulations were noted on the detached retinal surface and in the vitreous.
      Fundus autofluorescence imaging detected diffuse punctate accumulations, which
      produced hyperautofluorescence spots. Cytological examination of a vitreous
      sample detected CD68-positive and cytokeratin- and CD45-negative macrophages.
      These findings indicate that epithelial-to-mesenchymal transition occurred in the
      retinal pigment epithelium of our patient. [Ophthalmic Surg Lasers Imaging
      Retina. 2018;49:716-720.].

PMID- 30222809
TI  - Angiogenic Cytokine Profile of a Patient With Schwartz-Matsuo Syndrome.
AB  - A 36-year-old man was diagnosed with Schwartz-Matsuo syndrome and received a
      scleral buckle surgery. Photoreceptor outer segments in aqueous humor were
      examined under electron microscope to confirm the diagnosis. Afterwards, 17 human
      angiogenesis and growth factor biomarkers were chosen to make simultaneous
      quantification in aqueous humor, among which the authors demonstrated the
      remarkable high expression of angiopoietin-2 in aqueous humor. This is the first
      reported case of angiogenesis / growth factor biomarkers in aqueous humor of the
      Schwartz-Matsuo Syndrome patient. Angiopoietin-2 level significantly increased in
      this patient's aqueous humor, which helped the authors to illuminate the
      pathogenic mechanisms underlying Schwartz-Matsuo syndrome. [Ophthalmic Surg
      Lasers Imaging Retina. 2018;49:721-725.].

PMID- 30222810
TI  - Treatment Response in Sympathetic Ophthalmia as Assessed by Widefield OCT
      Angiography.
AB  - The authors report the widefield montage swept-source optical coherence
      tomography angiography (OCTA) findings in a 36-year-old male with sympathetic
      ophthalmia and illustrate the presence of multiple small areas of
      choriocapillaris flow voids that likely correspond to areas of choriocapillaris
      ischemia. Using sequential imaging, the authors observed that these flow voids
      improved following initiating of steroid and immunosuppressive therapy and almost
      completely resolved following 6 months of therapy with corresponding improvement
      in visual acuity. This report highlights the role of widefield montage OCTA to
      detect these likely ischemic changes within the choriocapillaris in sympathetic
      ophthalmia and demonstrates that they can be used as an anatomic marker to
      monitor treatment response. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:726
      730.].

PMID- 30222811
TI  - Large Traumatic Retinal Dialysis Associated With Prominent Vitreous Base
      Avulsion.
AB  - A 13-year-old female with a history of regressed retinopathy of prematurity
      presented with new-onset floaters after sustaining blunt force trauma to her left
      eye. Best-corrected visual acuity was 20/20 in both eyes (OU), with an
      intraocular pressure of 14 mm Hg and 15 mm Hg in the right eye (OD) and left eye
      (OS), respectively. Exam under anesthesia revealed an unremarkable anterior
      segment OU, including no hyphema or subluxated crystalline lens. Scleral
      depression OS demonstrated a retinal dialysis superotemporally (1-o'clock to 3
      o'clock) and nasally (7-o'clock to 10-o'clock) associated with a prominent
      vitreous base avulsion but no subretinal fluid (Figure). Scleral depression OD
      was unremarkable. Both areas of retinal dialysis OS were treated with three rows
      of indirect green laser photocoagulation posterior to the edge of the dialysis.
      [Ophthalmic Surg Lasers Imaging Retina. 2018;49:731.].

PMID- 30222812
TI  - Primary Vitreoretinal Lymphoma Presenting as a Posterior Capsule Plaque.
AB  - Primary vitreoretinal lymphoma (PVRL) can be a diagnostic challenge and commonly
      presents as a partially steroid-responsive vitritis or as subretinal cream
      colored infiltrates. The authors present a patient with PVRL who initially
      presented with bilateral vitritis; however, after two non-diagnostic vitrectomy
      specimens and two unremarkable brain MRIs, she was lost to follow-up. She
      presented 2.5 years later with a white plaque on the posterior capsule of her
      left intraocular lens, though the vitreous cavity was free of infiltrate. Repeat
      biopsy revealed diffuse large B-cell lymphoma, and brain MRI demonstrated an
      enhancing lesion of the cerebellum, consistent with primary central nervous
      system lymphoma.

PMID- 30222813
TI  - Outer Retinal Defects Represent a Normal Recovery Pathway Following Internal
      Limiting Membrane Peeling in Macular Hole Surgery.
AB  - BACKGROUND AND OBJECTIVE: To examine perioperative factors associated with the
      development of outer retinal defects (ORDs) following surgical repair of macular
      holes (MHs). PATIENTS AND METHODS: An institutional review board-approved,
      retrospective, interventional cohort study was conducted. Patients who underwent
      MH repair during a 5-year period were identified. Statistical analysis was
      conducted to detect significant perioperative associations to ORD development.
      RESULTS: One hundred twenty-four eyes were included, and 54% developed an ORD
      following surgery. These defects correlated with lower preoperative stage (P =
      .0057), preoperative phakia (P = .036), and lack of prior macular surgery (P =
      .0016). Patients in the ORD group had significantly better preoperative and
      postoperative visual acuity (P = .031 and P = .0004, respectively), but there was
      no difference in change in acuity from preoperatively to 3 months postoperatively
      when compared with control patients (P = 42). The majority (89%) of ORDs resolved
      by 24 months postoperatively. CONCLUSION: The development of ORDs appears to be
      correlated with several factors indicative of favorable overall eye health and
      less advanced pathology and may represent a normal state of recovery after MH
      repair with internal limiting membrane peeling. [Ophthalmic Surg Lasers Imaging
      Retina. 2018;49:e1-e8.].

PMID- 30222814
TI  - Repeatability of Split-Spectrum Amplitude-Decorrelation Angiography to Assess
      Capillary Perfusion Density Within Optical Coherence Tomography.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the repeatability of retinal thickness and
      vascular density measurements using split-spectrum amplitude-decorrelation
      angiography (SSADA) with optical coherence tomography (OCT). PATIENTS AND
      METHODS: Forty patients were divided into seven categories according to their
      diagnosis: no retinopathy (control), retinal vein occlusion, diabetes with no
      retinopathy, diabetes with retinopathy, non-exudative age-related macular
      degeneration (AMD), exudative AMD, and epiretinal membrane. Capillary density and
      retinal thickness measurements were taken and evaluated for reliability by
      determination of statistically significant differences and coefficient of
      variability (CoV) between measurements. RESULTS: No significant differences (P >
      .05) were found in any of the within-visit measurements. CoVs ranged from 0.26%
      to 52.76%, depending on the measure and the disease settings. CONCLUSION: The
      SSADA OCT angiography analysis has a low level of variability between
      measurements and, thus, is a reliable tool for evaluation of retinal perfusion.
      [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e9-e19.].

PMID- 30222815
TI  - Optical Coherence Tomography Angiography Findings in X-Linked Retinoschisis.
AB  - BACKGROUND AND OBJECTIVE: The aim of the study was to determine optical coherence
      tomography angiography (OCTA) findings and to identify mutations in the RS1 gene
      in a three-generation family with X-linked juvenile retinoschisis (XLRS).
      PATIENTS AND METHODS: Clinical and genetic assessments were performed in 12
      family members. OCTA was performed at baseline (12 members including cases and
      carriers) and after acetazolamide administration (three cases). Twenty healthy
      subjects (20 eyes, controls) were chosen for comparison. Molecular genetic
      analysis of the RS1 gene was performed in all family members. RESULTS: Deep
      capillary plexus density was reduced in cases compared with controls (P < .01)
      and was negatively related with retinal thickness (P < .05). After treatment,
      retinal thickness decreased (P < .05) and deep capillary plexus density increased
      (P < .05) in cases. In three cases and in four carriers, p.Arg197 His mutation
      was found. CONCLUSION: OCTA shows reduced macular deep vessel density in patients
      with XLRS probably related to vessel displacement and disruption due to schitic
      cysts. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e20-e31.].

PMID- 30222816
TI  - A Retrospective Analysis of the Timing of Initial Treatment of Bedside-Screened
      Versus Photographically Screened Eyes With Retinopathy of Prematurity.
AB  - BACKGROUND AND OBJECTIVE: A retrospective clinical study was performed to assess
      whether photographically screened and remotely read images for retinopathy of
      prematurity (ROP) allowed for timely and accurate diagnosis of treatment
      warranted ROP compared to bedside examination. PATIENTS AND METHODS: The study
      included 130 eyes of 65 premature neonates in born at William Beaumont Hospital,
      Royal Oak NICU. Bedside examined (2006 to 2010) and telemedicine screened (2010
      to 2014) neonates were compared to identify whether there is a statistical
      difference in postmenstrual age (PMA) at the time of treatment. RESULTS: One
      hundred thirty eyes of 65 infants met the inclusion and exclusion criteria.
      Thirty-five infants who needed laser treatment were screened bedside with an
      average PMA at treatment of 36.5 weeks. Thirty infants who needed treatment were
      photographically screened, with an average PMA at treatment of 36.4 weeks.
      Neither group had statistically different PMAs (P = .58). CONCLUSION: This study
      confirms that telemedicine also allows for appropriately timed treatment for
      early ROP. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e32-e35.].

PMID- 30222817
TI  - Microalbuminuria Is Associated With Early Retinal Neurodegeneration in Patients
      With Type 2 Diabetes.
AB  - BACKGROUND AND OBJECTIVE: To evaluate retinal layer changes in patients with type
      2 diabetes, microalbuminuria, and no diabetic retinopathy, and to investigate its
      possible relationship with age, gender, diabetes duration, urinary albumin
      excretion (UAE), glycosylated hemoglobin, and hypertension. PATIENTS AND METHODS:
      A prospective, cross-sectional study was performed in 60 patients divided into
      three groups: diabetic patients with normal UAE, diabetic patients with
      microalbuminuria, and controls. Retinal thickness was evaluated by Early
      Treatment Diabetic Retinopathy Study grid using spectral-domain optical coherence
      tomography. RESULTS: The average and sectoral macular thicknesses of the ganglion
      cell layer (GCL) were significantly thinner in the microalbuminuria group
      compared to normal UAE group and controls (P < .005). UAE was the only factor
      related to this reduction in a multiple linear regression analysis. CONCLUSIONS:
      The GCL thickness was reduced in eyes in patients with type 2 diabetes and
      microalbuminuria before clinical signs of diabetic retinopathy. Inner retinal
      neurodegeneration was independently associated with albuminuria. [Ophthalmic Surg
      Lasers Imaging Retina. 2018;49:e36-e43.].

PMID- 30222818
TI  - The Correlation of Pars Plana Incision and Transient Hypotony After Silicone Oil
      Removal.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the correlation between pars plana incision
      and transient hypotony after silicone oil removal in aphakic eyes PATIENTS AND
      METHODS:Twenty-two patients with aphakia and a high degree of myopia with
      silicone oil tamponade were recruited for this prospective study and randomly
      scheduled to two groups for silicone oil removal: 3.5-mm corneal incision with
      suture corneal or 20-gauge pars plana incision with suture. Intraocular pressure
      (IOP) was measured and fundus and anterior structure were examined preoperatively
      on the first, third, and seventh postoperative day and at 1 month after surgery.
      RESULTS: IOPs in the pars plana group were significantly lower than the corneal
      group on the first and third day after surgery (P < .001). Nine of the 11
      patients in the pars plana group suffered ciliary detachment accompanied by
      hypotony (IOP < 8 mm Hg), among whom three patients exhibited excessive hypotony
      (IOP < 5 mm Hg), whereas the ciliary bodies remained tightly attached and IOP was
      normal in the corneal group. Among these nine patients, six eyes were observed to
      have multiple silicone oil granules in the supraciliary cavity, three exhibited
      gaps of pars plana below the scleral incision site, and two had vitreous
      hemorrhage. Hypotony spontaneously relieved at the seventh postoperative day for
      all patients. CONCLUSION: Pars plana incision is the crucial cause of ciliary
      detachment and consequent transient hypotony after silicone oil removal. Using
      corneal limbus incision in patients with aphakic eyes to avoid the par plana
      incision is expected to reduce the incidence of hypotony with minimal
      complications. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e44-e51.].

PMID- 30222819
TI  - Reconsidering the Postoperative Day 0 Visit for Retina Surgery.
AB  - BACKGROUND AND OBJECTIVE: This study compares outcomes of patients who were
      examined on postoperative (PO) day 0 and PO day 1 following retina surgery.
      PATIENTS AND METHODS: A nonrandomized, comparative, retrospective series of one
      vitreoretinal surgeon was conducted on 166 patients with a PO day 0 visit
      (approximately 5 hours following surgery) and 428 patients with a PO day 1 visit.
      RESULTS: Among patients examined at PO day 0, 4.6% had hypotony (intraocular
      pressure [IOP] <= 5 mm Hg) and 1.8% needed intervention for elevated IOP (IOP >=
      30 mm Hg) compared with 1.6% and 4.0% of patients, respectively, examined on PO
      day 1. CONCLUSION: Following retina surgery, there is a similar percentage of
      patients with abnormal IOP when patients are examined on PO day 0 when compared
      with PO day 1. However, the rate of hypotony was statistically higher on PO day
      0, and there was a trend toward more elevated IOP on PO day 1. [Ophthalmic Surg
      Lasers Imaging Retina. 2018;49:e52-e56.].

PMID- 30222820
TI  - Closure of Large Chronic Macular Hole by Scleral Imbrication and Retinal
      Expansion.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study is to describe a new
      technique for the treatment of large, chronic macular hole (MH) using scleral
      imbrication and retinal expansion and to report the outcomes of MH closure.
      PATIENTS AND METHODS: This retrospective study demonstrates a procedure for
      correcting the disproportion between an area of stiff neurosensory retina and the
      inner scleral wall. Baseline MH parameters were collected. MH closure rate,
      visual outcomes, and biometry were reported at 6-month follow-up. RESULTS: MH
      closure was achieved in six out of seven patients (85.7%). Mean minimal hole
      diameter, base hole diameter, and MH index were 712 MUm +/- 136.8 MUm, 1,440 MUm
      +/- 444 MUm, and 0.27 MUm +/- 0.08 MUm, respectively. At 6-month follow-up,
      median logarithm of the minimum angle of resolution (logMAR) corrected distance
      visual acuity significantly improved from 1.2 (interquartile range [IQR] = 1.0 to
      1.6) preoperatively to 0.7 (IQR = 0.58 to 0.8) postoperatively (P = .018;
      Wilcoxon signed-rank test). CONCLUSION: This technique provided both satisfactory
      hole closure rates and acceptable structural outcomes. [Ophthalmic Surg Lasers
      Imaging Retina. 2018;49:e57-e64.].

PMID- 30222821
TI  - Stereological Method in Optical Coherence Tomography for In Vivo Evaluation of
      Laser-Induced Choroidal Neovascularization.
AB  - BACKGROUND AND OBJECTIVE: To evaluate a stereological method in optical coherence
      tomography (OCT) as an in vivo volume measurement of laser-induced choroidal
      neovascularization (L-CNV) lesion size. PATIENTS AND METHODS: Laser
      photocoagulation was applied in rats to rupture Bruch's membrane and induce L
      CNV. In vivo OCT images of neovascular lesions were acquired with a spectral
      domain OCT system at days 0, 3, 7, 10, and 14 after laser surgery. A
      stereological image-processing method was used to calculate lesion volumes from
      the OCT images. Rats were euthanized at day 14, and confocal microscopy was used
      to obtain accurate volume measurements of the lesions ex vivo. Lesion sizes
      calculated from OCT and confocal were compared. RESULTS: In vivo assessment by
      OCT allowed three distinct stages of L-CNV to be visualized: the initial early
      reaction, neovascular proliferation, and regression. At day 14, correlations
      between OCT and confocal lesion volumes showed a positive association (Pearson's
      r = 0.50, P < .01). Except for the largest lesions, volumes measured by OCT were
      statistically similar to those measured by the confocal gold standard (P = .90).
      CONCLUSION: The stereological approach used to measure neovascular lesion volume
      from OCT images offers an accurate means to track L-CNV lesion size in vivo.
      [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e65-e74.].

PMID- 30222822
TI  - Contralateral Autologous Internal Limiting Membrane Transplantation for Closure
      of a Refractory Macular Hole: Surgical Technique.
AB  - BACKGROUND AND OBJECTIVE: To determine the efficacy of a new surgical technique
      involving use of a contralateral autologous internal limiting membrane (ILM) free
      flap for closure of a refractory macular hole (MH). PATIENTS AND METHODS: Closure
      could not be achieved after several MH surgeries in a 72-year-old woman with an
      epiretinal membrane (ERM) in the right eye and a chronic MH in the left eye.
      Therefore, the authors performed surgery on the left eye using a contralateral
      autologous ILM free flap obtained during ERM surgery performed on the right eye.
      RESULTS: The refractory MH had disappeared, and the patient's corrected visual
      acuity was improved in both eyes by 4 months after surgery. CONCLUSION: When a
      suitable free flap cannot be obtained from the operated eye, contralateral
      autologous ILM transplantation has the potential to improve functional and
      anatomical outcomes in an eye with a refractory MH. [Ophthalmic Surg Lasers
      Imaging Retina. 2018;49:e75-e77.].

PMID- 30222823
TI  - Late-Stage Sjogren-Larsson Syndrome Maculopathy Imaged With OCT Angiography.
AB  - Three adult siblings with Sjogren-Larsson syndrome (SLS) demonstrated signs of
      late-stage SLS maculopathy, including intraretinal crystals, atrophic changes,
      and lipofuscin deposition. This first report of SLS maculopathy imaged with
      optical coherence tomography angiography revealed decreased retinal capillary
      density, vessel dilation, and increased flow voids in the superficial and deep
      capillary plexuses. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e78-e82.].

PMID- 30222824
TI  - Peripheral Persistent Fetal Vasculature: A Report of Three Cases.
AB  - The authors report three cases of persistent fetal vasculature (PFV) presenting
      with an atypical peripheral fibrovascular stalk. A 5-month-old with congenital
      exotropia with a vitreous hemorrhage in the right eye underwent vitrectomy, and a
      mid-peripheral vitreal vascular stalk was visualized within the area of
      hemorrhage. The second case is of an 8-year-old with two fetal vascular remnants
      in the right eye: (1) a stalk superotemporally extending from the pars plana to
      the mid-peripheral retina that was associated with a retinal break and (2) a
      focal lens opacity. The third case is a 12-year-old with a history of familial
      exudative vitreoretinopathy and peripapillary choroidal neovascular membrane
      found to have a peripheral vitreal stalk in the right eye. These cases
      demonstrate a rare form of PFV with primarily peripheral remnants. [Ophthalmic
      Surg Lasers Imaging Retina. 2018;49:e83-e88.].

PMID- 30222825
TI  - Autologous Neurosensory Retinal Free Flap Treatment for a Large Macular Hole.
AB  - A patient presented with a large chronic macular hole (MH) of 700 MUm. Best
      corrected visual acuity (BCVA) was 20/200. Since the MHs edges were attached and
      stiff, an autologous neurosensory retinal flap was harvested and placed into the
      MH to close it. Perfluoro-n-octane heavy liquid (PFC) was instilled over the flap
      and exchanged with silicone oil (1,000 cs). Seven days postoperatively, the MH
      was closed, with a BCVA of 20/80 that improved to 20/60 at months 1 and 3.
      Optical coherence tomography and angiography showed patch incorporation with
      fovea formation and normal circulation. [Ophthalmic Surg Lasers Imaging Retina.
      2018;49:e89-e92.].

PMID- 30222826
TI  - First Locally Acquired Congenital Zika Syndrome Case in the United States:
      Neonatal Clinical Manifestations.
AB  - In the spring of 2017, a full-term infant with microcephaly was delivered in
      South Florida. During first trimester, the mother presented with fever, nausea,
      and vomiting. She reported no foreign travel for herself or her partner. The
      infant's neurologic, ophthalmologic, neuroradiologic, and audiologic findings
      were highly suggestive of congenital Zika syndrome (CZS), confirmed by IgM
      antibodies and plaque reduction neutralization test. New observations, including
      peripheral temporal retinal avascularity and peripapillary retinal nerve fiber
      layer thinning, are presented from this first known case of non-travel-associated
      CZS in the United States. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e93
      e98.].

PMID- 30222827
TI  - Closure of Macular Hole Associated With Extreme High Myopia After Conventional
      Vitrectomy With ILM Peeling.
AB  - Macular hole associated with high myopia (MH-HM) and macular hole-associated
      retinal detachment (MH-RD) are two conditions found in eyes with pathologic
      myopia that often have poor postoperative outcomes. A discrepancy in size between
      the stretched retina and the posteriorly expanded sclera is a major factor in the
      pathogenesis. The authors report a case comprising both types of maculopathy, one
      in each eye. The eye with the MH-HM (right eye) represents the longest axial
      length ever reported to have successful macular hole closure by any technique.
      The authors conclude that traditional surgery can be an adequate treatment for
      such a challenging condition. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e99
      e101.].

PMID- 30222828
TI  - Fellow Eye Anti-VEGF 'Crunch' Effect in Retinopathy of Prematurity.
AB  - BACKGROUND AND OBJECTIVE: Anti-vascular endothelial growth factor (VEGF) therapy
      is increasing in popularity for treatment of retinopathy of prematurity (ROP).
      Despite many technical benefits, issues remain prompting further investigation.
      PATIENTS AND METHODS: Retrospective case report and literature review. RESULTS: A
      42-week-old postmenstrual age female with gestational age of 28 weeks and birth
      weight of 990 g presented with prominent progression of peripapillary purely
      tractional atypical stage 4A ROP in both eyes following intravitreal bevacizumab
      therapy in the right eye only. CONCLUSION: The authors present the first reported
      case, to their knowledge, of a "crunch" phenomenon tractional retinal detachment
      from fellow eye administration of bevacizumab. [Ophthalmic Surg Lasers Imaging
      Retina. 2018;49:e102-e104.].

PMID- 30222829
TI  - Anatomical Changes of Full-Thickness Macular Hole Documented by Microscope
      Integrated Spectral-Domain Optical Coherence Tomography.
AB  - BACKGROUND AND OBJECTIVE: To evaluate anatomical changes of idiopathic macular
      hole (MH) after internal limiting membrane removal and after passive suction at
      the hole's borders using microscope-integrated intraoperative optical coherence
      tomography (iOCT). PATIENTS AND METHODS: Five eyes of five subjects with full
      thickness idiopathic MH underwent phacoemulsification, intraocular lens
      implantation, pars plana vitrectomy, and internal limiting membrane (ILM)
      removal. iOCT was performed after ILM removal and after passive suction at the
      hole's borders. RESULTS: iOCT showed decreased MH diameter after ILM removal in
      all cases. Passive suction achieved complete apposition of borders. All cases
      presented successful postsurgical closure. CONCLUSIONS: iOCT provides anatomical
      information during MH surgery that may impact surgical decision-making by
      allowing a real-time evaluation of structures. iOCT with preservative-free
      triamcinolone acetonide enhanced ILM visualization. Its use is superior to iOCT
      alone for the identification of vitreomacular interface structures. [Ophthalmic
      Surg Lasers Imaging Retina. 2018;49:e105-e111.].

PMID- 30222830
TI  - Familial Exudative Vitreoretinopathy Imaged With Optical Coherence Tomography
      Angiography.
AB  - The authors present a case of a 29-year-old man who presented to the Department
      of Ophthalmology at their institution to complete a peripheral laser treatment in
      his left eye for familial exudative vitreoretinopathy complicated by tractional
      macular edema. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e112-e113.].

PMID- 30222831
TI  - Study of Tourniquet Use in Simulated First Aid: User Judgment.
AB  - BACKGROUND: The purpose of this study was to survey the judgments of tourniquet
      users in simulation to discern opportunities for further study. METHODS: The
      study design constituted two parts: questions posed to four tourniquet users and
      then their tourniquet use was surveyed in simulated first aid, where the users
      had to decide how to perform among five different cases. The questions addressed
      judged confidence, blood volumes, a reason bleeding resumes, regret of
      preventable death, hemorrhage assessment, need for side-by-side use of
      tourniquets, shock severity, predicting reliability, and difference in blood
      losses. The mechanical performance was tested on a manikin. Case 1 had no
      bleeding. Case 2 had limb-wound bleeding that indicated tourniquet use in first
      aid. Case 3 was like case 2, except the patient was a child. Case 4 was like case
      2, except caregiving was under gunfire. Case 5 was like case 4, but two
      tourniquets were to be used side by side. Each user made tests of the five cases
      to constitute a block. Each user had three blocks. Case order was randomized
      within blocks. The study had 60 tests. RESULTS: In answering questions relevant
      to first-aid use of limb tourniquets, judgments were in line with previous
      studies of judgment science, and thus were plausibly applicable. Mechanical
      performance results on the manikin were as follows: 38 satisfactory, 10
      unsatisfactory (a loose tourniquet and nine incorrect tourniquet placements), and
      12 not applicable (case 1 needed no mechanical intervention). For cases 1 to 5,
      satisfactory results were: 100%, 83%, 100%, 75%, and 58%, respectively. For
      blocks 1 to 3, satisfactory results were 50%, 83%, and 83%, respectively.
      CONCLUSION: For tourniquet use in simulated first aid, the results are plausibly
      applicable because user judgments were coherent with those in previous studies of
      judgment science. However, the opportunities for further studies were noted.

PMID- 30222832
TI  - Your Metric Matters! Choose Wisely to Assess User Performance With Tourniquets in
      Simulated First Aid.
AB  - BACKGROUND: Readiness to perform lifesaving interventions during emergencies is
      based on a person's preparation to proficiently execute the skills required.
      Graphically plotting the performance of a tourniquet user in simulation has
      previously aided us in developing our understanding of how the user actually
      behaves. The purpose of this study was to explore performance assessment and
      learning curves to better understand how to develop best teaching practices.
      METHODS: These were retrospective analyses of a convenience sample of data from a
      prior manikin study of 200 tourniquet uses among 10 users. We sought to generate
      hypotheses about performance assessments relevant to developing best teaching
      practices. The focus was on different metrics of user performance. RESULTS: When
      one metric was chosen over another, failure counts summed cumulatively over 200
      uses differed as much as 12-fold. That difference also indicated that the degree
      of challenge posed to user performance differed by the metric chosen. When we
      ranked user performance with one metric and then with another, most (90%; nine of
      10) users changed rank: five rose and four fell. Substantial differences in
      performance outcomes resulted from the difference in metric chosen, which, in
      turn, changed how the outcome was portrayed and thus interpreted. Hypotheses
      generated included the following: The usefulness of a specific metric may vary by
      the user's level of skill from novice to expert; demonstration of the step order
      in skill performance may suffice for initial training of novices; a mechanical
      metric of effectiveness, like pulse stoppage, may aid in later training of
      novices; and training users how to practice on their own and self-assess
      performance may aid their self-development. CONCLUSION: The outcome of the
      performance assessments varied depending on the choice of metric in this study of
      simulated use of tourniquets.

PMID- 30222833
TI  - Mechanical Forces Experienced by Simulated Patients Evacuated During Dismounted
      Military Movement in Mountainous Terrain.
AB  - BACKGROUND: Given a denied or resource-limited area of operations, when air
      medical evacuation would require extended delay, should dismounted movement
      through difficult terrain dissuade an attempt of immediate ground evacuation?
      Understanding the magnitude of external forces during dismounted movement would
      inform planning in such circumstances. OBJECTIVES: We assessed the mechanical
      impact experienced during dismounted evacuation from mountainous terrain. We also
      describe a protocol using a portable accelerometer to evaluate evacuation.
      MATERIALS AND METHODS: A triaxial accelerometer and a semiflexible litter were
      used to collect data during the Army Mountain Warfare School Rough Terrain
      Evacuation Course. We used the generalized extreme value (GEV) distribution,
      using maximum likelihood estimation, to model maximum acceleration values.
      RESULTS: It was determined that the accelerometer should be mounted directly onto
      a mannequin when using semiflexible litters. GEV analysis from a mannequin
      mounted trial revealed that for 1-minute evacuation intervals, 10% would have a
      maximum acceleration over a value between 2.4g and 3.7g. This interval
      encompasses the maximum acceleration from evacuation using a Mine-Resistant
      Ambush Protected (MRAP) vehicle, measured by the US Army Aeromedical Research
      Laboratory. The peak acceleration from a 75-minute, mannequin-mounted trial was
      5.5g, approximately twice as large as the MRAP maximum. CONCLUSION: For the
      evacuee, the acceleration experienced during dismounted evacuation in mountainous
      terrain can be comparable to MRAP evacuation, especially with sufficient planning
      that avoids points of maximum impact. Leaders can consider this comparison during
      planning.

PMID- 30222834
TI  - Comparison of Scapular Manipulation With External Rotation Method of Reduction of
      Acute Anterior Shoulder Dislocation for Sedation Requirements and Success Rates.
AB  - BACKGROUND: Anterior shoulder dislocation is a common sports-related
      musculoskeletal injury. Various methods have been described for reduction of the
      dislocation. A method that requires less sedation without compromising the
      success rate is likely to be highly useful in austere and prehospital settings.
      This study compares scapular manipulation with external rotation method for
      requirement of sedation and success rates. METHODS: Forty-six patients with
      anterior shoulder dislocation were allocated alternatively to reduction using
      either scapular manipulation (SMM) or external rotation (ERM) techniques. The
      groups were compared for sedation requirements, pain scores, and success rates.
      RESULTS: Reductions using SMM had fewer requirements for sedation (13% versus
      39%; p < .05) and higher first-pass success rates (87% versus 61%; p < .05) as
      compared with ERM for anterior shoulder dislocation reduction. The numeric rating
      score of pain during reduction procedures was less in SMM (mean, 1.65 [standard
      deviation, 1.6]) than in ERM group (mean, 4.30 [standard deviation, 1.8]; p <
      .01). CONCLUSION: The SMM required less sedation and had higher first-pass
      success rates than ERM for reduction of anterior shoulder dislocation. The SMM is
      thus likely to be of advantage in resource-limited austere settings.

PMID- 30222835
TI  - Worldwide Case Reports Using the iTClamp for External Hemorrhage Control.
AB  - BACKGROUND: Historically, hemorrhage control strategies consisted of manual
      pressure, pressure dressings, gauze with or without hemostatic ingredients for
      wound packing, or the use of tourniquets. The iTClamp is a relatively new
      alternative to stop external bleeding. METHODS: An anonymous survey was used to
      evaluate the outcomes of the iTClamp in worldwide cases of external bleeding.
      RESULTS: A total of 245 evaluable applications were reported. The iTClamp stopped
      the bleeding in 81% (n = 198) of the cases. Inadequate bleeding control was
      documented in 8% (n = 20) and in the remaining 11% (n = 27), bleeding control was
      not reported. The top three anatomic body regions for iTClamp application were
      the scalp, 37% (n = 91); arm, 20% (n = 49); and leg, 19% (n = 46). In 26% of the
      reported cases (direct pressure [23% (n = 63)] and tourniquets [3% (n = 8]),
      other techniques were abandoned in favor of the iTClamp. Conversely, the iTClamp
      was abandoned in favor of direct pressure 11 times (4.4%) and abandoned in favor
      of a tourniquet three times (1%). CONCLUSION: The iTClamp appears to be a fast
      and reliable device to stop external bleeding. Because of its function and
      possible applications, it has potential to lessen the gap between and add to the
      present selection of devices for treatment of external bleeding.

PMID- 30222836
TI  - Swedish Specialized Boarding Element Members' Experiences of Naval Hostile Duty.
AB  - BACKGROUND: The Swedish naval specialized boarding element participated in
      Operation Atalanta in 2013 to mitigate piracy by escorting and protecting ships
      included in the United Nations World Food Program in the Indian Ocean. We
      describe the experiences of the Swedish naval specialized boarding-element
      members during 4 months of international naval hostile duty. Some studies have
      reported experiences of naval duty for the Coast Guard or the merchant fleet;
      however, we did not find any studies that identified or described experiences of
      long-time duty onboard ship for the naval armed forces. MATERIALS AND METHODS:
      The respondents wrote individual notes of daily events while onboard.
      Conventional content analysis was used on the collected data, using an inductive
      approach. RESULTS: The findings revealed three broad themes: military
      preparedness, coping with the naval context, and handling physical and mental
      strain. Different categories emerged indicating that the participants need the
      ability to adapt to the naval environment and to real situations. CONCLUSION: The
      Swedish naval forces should train their specialized element members in coping
      strategies.

PMID- 30222837
TI  - A Pilot Study of Four Intraosseous Blood Transfusion Strategies.
AB  - BACKGROUND: Intraosseous (IO) access is used by military first responders
      administering fluids, blood, and medications. Current IO transfusion strategies
      include gravity, pressure bags, rapid transfusion devices, and manual push-pull
      through a three-way stopcock. In a swine model of hemorrhagic shock, we compared
      flow rates among four different IO blood transfusion strategies. METHODS: Nine
      Yorkshire swine were placed under general anesthesia. We removed 20 to 25mL/kg of
      each animal's estimated blood volume using flow of gravity. IO access was
      obtained in the proximal humerus. We then autologously infused 10 to 15mL/kg of
      the animal's estimated blood volume through one of four randomly assigned
      treatment arms. RESULTS: The average weight of the swine was 77.3kg
      (interquartile range, 72.7kg-88.8kg). Infusion rates were as follows: gravity,
      5mL/min; Belmont rapid infuser, 31mL/min; single-site pressure bag, 78mL/min;
      double-site pressure bag, 103mL/min; and push-pull technique, 109mL/min. No
      pulmonary arterial fat emboli were noted. CONCLUSION: The optimal IO transfusion
      strategy for injured Servicemembers appears to be single-site transfusion with a
      10mL to 20mL flush of normal saline, followed immediately by transfusion under a
      pressure bag. Further study, powered to detect differences in flow rate and
      clinical complications. is required.

PMID- 30222838
TI  - Implementation and Evaluation of a First-Responder Bleeding-Control Training
      Program in a Rural Police Department.
AB  - BACKGROUND: In the prehospital environment, nonmedical first responders are often
      the first to arrive on the scene of a traumatic event and must be prepared to
      provide initial care at the point of injury. In civilian communities, these
      nonmedical first responders often include law enforcement officers. Hemorrhage is
      a major cause of death in trauma, and many of these deaths occur in the
      prehospital environment; therefore, prehospital training efforts should be
      directed accordingly toward bleeding control. METHODS: A bleeding control
      training program was implemented and evaluated in a rural police department in
      Pinehurst, North Carolina, from February to April 2017. A repeated measures
      observational study was conducted to evaluate the training program. Measured were
      self-efficacy (pre- and post-test), knowledge (pretest, post-test 1 [immediate],
      post-test 2 [at 4 weeks]), and limb-tourniquet application time (classroom,
      simulation exercise). RESULTS: The study population was composed of 28 police
      officers (92.9% male) whose median age was 37 (interquartile range, 22-55) years.
      Mean self-efficacy scores, equating to user confidence and the decision to
      intervene, increased from pre- to post-training (34.54 [standard deviation (SD)
      4.16] versus 35.62 [SD 4.17]; p = .042). In addition, mean knowledge test scores
      increased from pre- to immediately post-training (75.00 [SD 16.94] versus 85.83
      [SD 11.00]; p = .006), as well as from preto 4 weeks post-training (75.00 [SD
      16.94] versus 84.17 [SD 11.77]; p = .018). Lower limb-tourniquet application
      times were more rapid in the classroom than during the simulation exercise (23.06
      seconds [SD 7.68] versus 31.91 seconds [SD 9.81]; p = .005). CONCLUSION: First
      responder bleeding-control programs should be initiated and integrated at the
      local level throughout the Nation. Implementation and sustainment of such
      programs in police departments can save lives and enhance existing law
      enforcement efforts to protect and serve communities.

PMID- 30222839
TI  - Facial Trauma Care in the Austere Environment.
AB  - As the United States continues to increase its use of Special Operations Forces
      worldwide, treatment of craniomaxillofacial (CMF) trauma must be adapted to meet
      the needs of the warfighter. The remoteness of Special Operations can result in
      potentially longer times until definitive treatment may be reached. A significant
      portion of Servicemembers incur injury to the CMF region (42%). Severe CMF trauma
      can result in substantial hemorrhage and airway compromise. These can be
      immediately life threatening and must be addressed expeditiously. Numerous
      devices and techniques for airway management have been made available to the
      forward provider. A thorough review of nonsurgical and surgical airway management
      of the patient with facial injury for the forward provider and providers at
      receiving facilities is provided in this article. Techniques to address flail
      segments of the facial skeleton are critical in minimizing airway compromise in
      these patients. There are many methods to control hemorrhage from the head and
      neck region. Hemorrhage control is critical to ensure survival in the austere
      environment and allow for transport to a definitive care facility. Associated
      injuries to the cervical spine, globe, skull base, carotid artery, and brain must
      be carefully evaluated and addressed in these patients. Management of vision-
      threatening orbital compartment syndrome is critical in patients with CMF
      injuries. Because the head and neck region remains relatively vulnerable in the
      warfighter, combat CMF trauma will continue to occur. Forward providers will
      benefit from a review of the acute treatment of CMF traumatic injury. Properly
      triaging and treating facial injuries is necessary to afford the best chance of
      survival for patients with a devastating combat CMF injury.

PMID- 30222840
TI  - Chemical Contamination Transfer in the Management of War Casualties.
AB  - The use of chemical weapons agents (CWAs) was suspected in recent conflicts,
      during international conflicts, terrorist attacks, or civil wars. Little is known
      about the prevention needed for caregivers exposed to the risk of contamination
      transfer. We present a case of chemical contamination of health servicemembers
      during the management of casualties.

PMID- 30222841
TI  - Does Pain Have a Role When It Comes to Tourniquet Training?
AB  - BACKGROUND: One of the greatest conundrums with tourniquet (TQ) education is the
      use of an appropriate surrogate of hemorrhage in the training setting to
      determine whether a TQ has been successfully used. At our facility, we currently
      use loss of audible Doppler signal or loss of palpable pulse to represent
      adequate occlusion of vasculature and thus successful TQ application. We set out
      to determine whether pain can be used to indicate successful TQ application in
      the training setting. METHODS: Three tourniquet systems (a pneumatic tourniquet,
      Combat Application Tourniquet(r) [C-A-T], and Stretch Wrap and Tuck TourniquetTM
      [SWAT-T]) were used to occlude the arterial vasculature of the left upper arm
      (LUA), right upper arm (RUA), left forearm (LFA), right forearm (RFA), right
      thigh (RTH), and right calf (RCA) of 41 volunteers. A 4MHz, handheld Doppler
      ultrasound was used to confirm loss of Doppler signal (LOS) at the radial or
      posterior tibial artery to denote successful TQ application. Once successful
      placement of the TQ was noted, subjects rated their pain from 0 to 10 on the
      visual analog scale. In addition, the circumference of each limb, the pressure
      with the pneumatic TQ, number of twists with the C-A-T, and length of TQ used for
      the SWAT-T to obtain LOS was recorded. RESULTS: All 41 subjects had measurements
      at all anatomic sites with the pneumatic TQ, except one participant who was
      unable to complete the LUA. In total, pain was rated as 1 or less by 61% of
      subjects for LUA, 50% for LFA, 57.5% for RUA, 52.5% RFA, 15% for RTH, and 25% for
      RCA. Pain was rated 3 or 4 by 45% of subjects for RTH. For the C-A-T, data were
      collected from 40 participants. In total, pain was rated as 1 or less by 57.5%
      for the LUA, 70% for the LFA, 62.5% for the RUA, 75% for the RFA, 15% for the
      RTH, and 40% for the RCA. Pain was rated 3 or 4 by 42.5%. The SWAT-T group
      consisted of 37 participants for all anatomic locations. In total, pain was rated
      as 1 or less by 27% for LUA, 40.5% for the LFA, 27.0% for the RUA, 43.2 for the
      RFA, 18.9% for the RTH, and 16.2% for the RCA. Pain was rated 5 by 21.6% for RTH
      application, and 3 or 4 by 35%. CONCLUSION: The unexpected low pain values
      recorded when loss of signal was reached make the use of pain too sensitive as an
      indicator to confirm adequate occlusion of vasculature and, thus, successful TQ
      application.

PMID- 30222843
TI  - 2018 Research Abstracts Selection for Podium or Poster Presentation.

PMID- 30222842
TI  - The Combat Application Tourniquet Versus the Tactical Mechanical Tourniquet.
AB  - BACKGROUND: Exsanguination from limb injury is an important battlefield
      consideration that is mitigated with the use of emergency tourniquets. The Combat
      Application Tourniquet (C-A-T(r)) is the current British military standard
      tourniquet. METHODS: We tested the self-application of a newer tourniquet system,
      the Tactical Mechanical Tourniquet (TMT), against self-application of the C-A-T.
      A total of 24 healthy British military volunteers self-applied the C-A-T and the
      TMT to their mid thigh in a randomized, sequential manner. Popliteal artery flow
      was monitored with a portable ultrasound machine, and time until arterial
      occlusion was measured. Pain scores were also recorded. Results The volunteers
      allowed testing on their lower limbs (n = 48 legs). The C-A-T was applied
      successfully to 22 volunteers (92%), and the TMT was successfully applied to 17
      (71%). Median time to reach complete arterial occlusion was 37.5 (interquartile
      range [IQR], 27-52) seconds with the C-A-T, and 35 (IQR, 29-42) seconds with the
      TMT. The 2.5-second difference in median times was not significant (rho = .589).
      The 1-in-10 difference in median pain score was also not significant (rho =
      .656). The success or failure of self-application between the two tourniquet
      models as assessed by contingency table was not significant (p= .137).
      CONCLUSION: The TMT is effective when self-applied at the mid thigh. It does not
      offer an efficacy advantage over the C-A-T.

PMID- 30222844
TI  - Cognitive Agility as a Factor in Human Performance Optimization.
AB  - Cognitive agility reflects the capacity of an individual to easily move back and
      forth between openness and focus. The concept is being translated into a tool to
      help train leaders to perform well in the "dynamic decision-making context."
      Cognitive agility training (CAT) has the potential to increase emotional
      intelligence by improving an individual's ability to toggle between highly
      focused states to levels of broad, outward awareness, which should enable dynamic
      decision-making and enhance personal communication skills. Special Operations
      Forces (SOF) Operators must work in rapidly evolving, complex environments
      embedded with multiple high-risk factors. Generally, success in these operational
      environments requires the ability to maintain highly focused states. However, SOF
      Operators must also be able to transition rapidly back to their roles within
      their families, where a more outwardly aware state is needed to allow flexibility
      in emotional responses. CAT addresses these seemingly conflicting requirements.
      Successful CAT must reflect the methodologies and culture already familiar within
      the SOF community (i.e., "live" scenario-based activities) to replicate
      challenges they may encounter when operationally deployed and when at home. This
      article provides an overview of cognitive agility, the potential benefits,
      applications that could be used for training SOF Operators to improve their
      cognitive agility to optimize performance, and sample training scenarios. The
      issue of what metrics to use is also discussed.

PMID- 30222845
TI  - Norovirus.

PMID- 30222846
TI  - Osteoarthritis: Pathophysiology, Prevalence, Risk Factors, and Exercise for
      Reducing Pain and Disability.
AB  - Osteoarthritis (OA) is a disorder involving deterioration of articular cartilage
      and underlying bone and is associated with symptoms of pain and disability. The
      incidence of OA in the military increased over the period 2000 to 2012 and was
      the first or second leading cause of medical separations in this period. Risk
      factors for OA include older age, black race, genetics, higher body mass index,
      prior knee injury, and excessive joint loading. Animal studies indicate that
      moderate exercise can assist in maintaining normal cartilage, and individuals
      performing moderate levels of exercise show little evidence of OA. There is
      considerable evidence that among individuals who develop OA, moderate and regular
      exercise can reduce pain and disability. There is no firm evidence that any
      particular mode of exercise (e.g., aerobic training, resistance exercise) is more
      effective than another for reducing OA-related pain and disability, but limited
      research suggests that exercise should be lifelong and conducted at least three
      times per week for optimal effects.

PMID- 30222847
TI  - How the International Special Training Centre Is Training World-Class Medics: An
      Outline of the NATO Special Operations Combat Medic Course.
AB  - The North Atlantic Treaty Organization (NATO) Special Operations Combat Medic
      (NSOCM) course is specifically designed to train 24 highly selected Special
      Operations Forces (SOF) members to treat trauma and nontrauma patients who have
      life-threatening diseases and/or injuries. The NSOCM course is held at the
      International Special Training Centre (ISTC) in Pfullendorf, Germany, and
      exemplifies ISTC's mission to build interoperability and strengthening alliances
      between multinational partners. The 24-week NSOCM course is taught by subject
      matter experts and SOF members from around the globe. Building interoperability
      and capacity with common NATO standards is crucial to medical support of all
      future SOF missions where military units and other small elements will be vitally
      dependent on each other for combined missions at the regional, national, or NATO
      level. A better understanding and knowledge of the current SOF medic role and the
      capabilities they need to bring to the battlefield will help advance their scope
      from the "classic" trauma scenarios to the more advanced clinical medicine and
      prolonged field care situations. The NSOCM must become a critical-thinker and be
      able to recognize and treat these health risks and conditions in remote, austere
      environments, finding the right solution with a limited arsenal at their
      disposal. The ISTC-NSOCM course is designed to help bridge this gap and raise
      situational awareness for the NATO on-the-ground medical professionals to ensure
      "the more they know the more apt they are to save a life." In essence, it is
      ISTC's goal to meet these challenges by training NSOCMs to meet these
      multidimensional demands. This article outlines ISTC's development and design of
      the NSOCM course and new adaptations as we move forward into our third year of
      training world-class medics.

PMID- 30222848
TI  - Damage Control Resuscitation in Prolonged Field CareDamage Control Resuscitation
      in Prolonged Field Care.

PMID- 30222849
TI  - Prolonged Field Care in Support of Operation Inherent Resolve, 2016.
AB  - The authors present their experience in emergency and longterm medical care by
      Special Operations Forces (SOF) medical providers in an austere environment. In
      this case, a Special Forces Operational Detachment-Alpha (SFOD-A) was deployed in
      support of Operation Inherent Resolve, partnered with indigenous combat forces.

PMID- 30222850
TI  - Knowledge Versus Suspicion.

PMID- 30222851
TI  - Draw-over Anesthesia Bringing the "Dark Art" Back Into the Light.

PMID- 30222852
TI  - Tactical Combat Casualty Care for Medical Personnel (TCCC-MP): Recommended Post
      Course Metrics (24 July 2018).

PMID- 30222853
TI  - Please, more tears: a case of a moth feeding on antbird tears in central
      Amazonia.
AB  - The vertebrate tear-feeding (lachryphagy) on birds by moths is a rarely
      documented event, with only two known records from Madagascar (Hilgartner et al.
      2007) and Colombia (Sazima 2015). In these events, the moths insert their
      morphologically adapted proboscis (Zaspel et al. 2011) on the target species'
      ocular area to feed on their tears (Hilgartner et al. 2007, Zenker et al. 2011).
      Although one currently known moth is an obligatory lachryphagous species (Waage
      1979), most of them feed on tears as a supplementary method to obtain nutrients,
      mainly sodium and proteins (Plotkin and Goddard 2013). This article is protected
      by copyright. All rights reserved.

PMID- 30222854
TI  - Valaciclovir: a culprit drug for drug reaction with eosinophilia and systemic
      symptoms not to be neglected. Three cases.

PMID- 30222855
TI  - Noninvasive prenatal diagnosis by cell-free DNA screening for fetomaternal HPA-1a
      platelet incompatibility.
AB  - BACKGROUND: The development of new noninvasive approaches for the diagnosis of
      human platelet antigen (HPA)-1 fetomaternal incompatibility has become of great
      interest. These approaches allow determination of whether the fetus is
      incompatible or not with the mother and a decision on antenatal therapy to avoid
      fetal or neonatal alloimmune thrombocytopenia (FNAIT). The objective of this work
      was to perform rapid, noninvasive prenatal test for HPA-1ab fetal antigen
      detection after the detection of an HPA-1-homozygous mother by using plasma cell
      free DNA (cfDNA). STUDY DESIGN AND METHODS: The HPA-1 genotypes of 142 pregnant
      women and 17 nonpregnant controls were retrospectively determined by high
      resolution melting (HRM) polymerase chain reaction (PCR). Coamplification at
      lower denaturation temperature (COLD) HRM PCR was performed to determine the
      fetal genotype analyzing cfDNA from all HPA-1bb pregnant women. RESULTS: After
      the HRM analysis, the following genotypes were identified: HPA-1aa (71.13%), HPA
      1bb (2.8%), and HPA-1ab (26.06%). Four HPA-1bb-homozygous pregnant women were
      carrying an incompatible fetus. Plasma samples from these mothers were analyzed
      by HRM COLD-PCR. Homozygous HPA-1bb pregnant women carrying an HPA-1ab
      heterozygous fetus did not group with either the HPA-1ab or the HPA-1bb controls.
      Thus, COLD-PCR analysis allows the detection of HPA-1ab-heterozygous fetuses
      carried by homozygous mothers during first weeks of pregnancy. CONCLUSION: The
      fetal genotype from HPA-1bb-homozygous women was detected by a noninvasive
      prenatal test as soon as 12 weeks of gestation.

PMID- 30222856
TI  - Secondary thrombotic microangiopathy with severely reduced ADAMTS13 activity in a
      patient with Capnocytophaga canimorsus sepsis: a case report.
AB  - BACKGROUND: The Gram-negative bacillus Capnocytophaga canimorsus may cause a
      severe illness resembling thrombotic thrombocytopenic purpura (TTP). The
      pathogenesis and optimal therapy of this secondary thrombotic microangiopathy
      (TMA) remain uncertain. CASE REPORT: A 63-year-old Caucasian man was admitted
      with suspicion for TTP, but blood cultures grew C. canimorsus. Initial
      investigations revealed severe thrombocytopenia, a disintegrin and
      metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13)
      activity level of less than 1%, and strongly elevated D-dimer and lactate
      dehydrogenase levels. He made a full recovery with antibiotics and plasma
      infusion for 3 days. Plasmapheresis was not performed. Retrospective
      determination of serial ADAMTS13 activity levels revealed that ADAMTS13 activity
      had already increased to 25% at the start of plasma infusion. CONCLUSION: This
      case highlights that a C. canimorsus sepsis may cause a secondary TMA with a
      severe ADAMTS13 deficiency. It also illustrates that the adjunctive role of
      plasma exchange or plasma infusion is doubtful as ADAMTS13 activity levels
      increased with antibiotics alone.

PMID- 30222857
TI  - Rifampicin Alters Metformin Plasma Exposure but Not Blood Glucose Levels in
      Diabetic Tuberculosis Patients.
AB  - The pharmacokinetic (PK) and clinical implications of combining metformin with
      rifampicin are relevant to increasing numbers of patients with diabetic
      tuberculosis (TB) across the world and are yet unclear. We assessed the impact of
      rifampicin on metformin PKs and its glucose-lowering effect in patients with
      diabetic TB by measuring plasma metformin and blood glucose during and after TB
      treatment. Rifampicin increased metformin exposure: plasma area under the plasma
      concentration-time curve from time point 0 to the end of the dosing interval
      (AUC0-tau ) and peak plasma concentration (Cmax ) geometric mean ratio (GMR;
      during vs. after TB treatment) were 1.28 (90% confidence interval (CI) 1.13-1.44)
      and 1.19 (90% CI 1.02-1.38; n = 22). The metformin glucose-lowering efficacy did
      not change (Deltaglucose - Cmax ; P = 0.890; n = 18). Thus, we conclude that
      additional glucose monitoring in this population is not warranted. Finally, 57%
      of patients on metformin and rifampicin, and 38% of patients on metformin alone
      experienced gastrointestinal adverse effects. Considering this observation, we
      advise patients to take metformin and rifampicin with food and preferably
      separated in time. Clinicians could consider metoclopramide if gastrointestinal
      adverse effects occur.

PMID- 30222858
TI  - Natural Environments Near Schools: Potential Benefits for Socio-Emotional and
      Behavioral Development in Early Childhood.
AB  - Features of the natural environment such as tree canopy and green space have been
      found to promote health and well-being; however, minimal research has
      investigated potential benefits of nature near schools for early childhood
      development. This study examined differences in teacher ratings of preschoolers'
      socio-emotional and behavioral functioning in relation to the presence of natural
      elements (e.g., trees, parks) near children's homes and schools. Students'
      development of emotional and behavioral regulatory skills was the greatest when
      there were high levels of tree canopy either at home or school. Additionally,
      students developed greater independence and social skills when their schools were
      in neighborhoods with limited impervious surface (e.g., concrete); this trend was
      the most pronounced for students from neighborhoods low in impervious surface.
      Further, results suggested that associations with tree canopy may fluctuate
      seasonally (i.e., stronger relationships in the spring) and that the potential
      impact of school nature may depend on levels of home nature exposure. Although
      not yielding causal evidence regarding the impact of nature exposure or the
      effectiveness of greening interventions, findings suggest that school
      administrators and city planners could collaborate to maximize potential benefits
      of greening efforts near schools or within their catchment zones.

PMID- 30222859
TI  - Identification of a novel B allele with multiple missense mutations in a Chinese
      family with a Bw phenotype.

PMID- 30222860
TI  - Comparative evaluation of platelet counts in two hematology analyzers and
      potential effects on prophylactic platelet transfusion decisions.
AB  - BACKGROUND: Decisions on prophylactic platelet (PLT) transfusions are generally
      based on the recipient's PLT count, but few clinicians are aware of precision and
      accuracy of the PLT counting methods used by the clinical laboratory. Each PLT
      counting technology has its specific inaccuracy, especially in thrombocytopenic
      samples and therefore may impact decisions on PLT transfusions. STUDY DESIGN AND
      METHODS: Five routine PLT counting methods available in two hematology analyzers
      (Sysmex XN-2000 and Abbott CELL-DYN Sapphire) were investigated (impedance and
      optical on both analyzers and fluorescent on XN-2000), using the CD61 immunologic
      PLT method as a reference. The impact of counting inaccuracy on imaginary
      transfusion decisions was examined at various common PLT thresholds. RESULTS: In
      total 341 samples were analyzed, 178 of which had PLT counts of less than 35 *
      109 /L. Despite excellent overall correlation with the reference method (r >
      0.99), thrombocytopenic samples showed only modest correlation for impedance and
      XN-2000 optical methods. Sapphire optical and XN-2000 fluorescent methods
      correlated very well with the reference, albeit with bias in the very low range.
      We noticed potential risk of undertransfusion (ranging from 2% to 90%), depending
      on the threshold used. The risk of overtransfusion was small (<10%). CONCLUSIONS:
      The XN-2000 fluorescent PLT counting method showed excellent correlation with the
      CD61 reference count, closely followed by the CELL-DYN Sapphire optical method.
      XN-2000 impedance and optical and Sapphire impedance methods are not accurate
      enough for basing transfusion decisions on. Only XN-2000 fluorescent, Sapphire
      optical, and CD61 methods are sufficiently accurate for making appropriate
      clinical decisions in patients with severe thrombocytopenia.

PMID- 30222861
TI  - Does using applied muscle tension at strategic time points during donation reduce
      phlebotomist- and donor-reported vasovagal reaction rates? A three-armed
      randomized controlled trial.
AB  - BACKGROUND: Vasovagal reactions (VVRs) have a negative impact on donor safety and
      return. Applied muscle tension (AMT) increases blood pressure temporarily and has
      been suggested as a way to reduce donors' risk of VVRs. This study evaluated
      whether using AMT at three different time points during the donation procedure
      reduces the VVR symptoms reported by donors and the VVR reactions recorded by
      phlebotomists. STUDY DESIGN AND METHODS: A three-arm, multicenter, open-label
      randomized controlled trial was used to compare VVR symptoms and reaction rates
      between those practicing AMT during the entire donation (n = 244) to practicing
      AMT at VVR high-risk time points (n = 250) to a standard blood donation control
      group (n = 240). All participants were asked to drink 500 mL of water in the
      waiting area, and an even distribution of new and repeat donors was sought across
      conditions. RESULTS: Across all conditions, donors reported few VVR symptoms and
      the rate of reporting did not differ significantly across conditions. However,
      donors who practiced AMT at strategic time points had a significantly lower
      number of phlebotomist-registered VVRs in comparison to the other two study
      groups, with these rates not varying by sex or donor status. Greater compliance
      by donors with AMT instructions was observed in those asked to practice AMT at
      strategic time points compared to those asked to practice AMT during the entire
      donation. CONCLUSION: Practicing AMT at VVR high-risk time points reduces the
      number of phlebotomist-registered VVRs.

PMID- 30222862
TI  - Nutrients, but not genetic diversity, affect Gracilaria chilensis (Rhodophyta)
      farming productivity and physiological responses.
AB  - In terrestrial plants, it is well known that genetic diversity can affect
      responses to abiotic and biotic stress and have important consequences on
      farming. However, very little is known about the interactive effects of genetic
      and environmental factors on seaweed crops. We conducted a field experiment on
      Gracilaria chilensis to determine the effect of heterozygosity and nutrient
      addition on two southern Chilean farms: Ancud and Chaica. In addition to growth
      rate and productivity, we measured photosynthetic responses, photosynthetic
      pigment concentration (chlorophyll a and phycobiliproteins), C:N ratio (C:N), and
      epiphytic load. Nutrient addition affected the growth rate, productivity,
      phycobilin, and C:N content, but not the epiphytic load. These results were
      independent of the heterozygosity of the strains used in the experiments.
      Interestingly, depending on the sampled sites, distinct photosynthetic responses
      (i.e., maximal quantum yield, Fv /Fm , and maximal electron transport rate,
      ETRmax ) to nutrient addition were observed. We propose that thallus selection
      over the past few decades may have led to ecological differentiation between G.
      chilensis from Chaica and Ancud. The lack of effect of heterozygosity on growth
      and physiological responses could be related to the species domestication history
      in which there is a limited range of genetic variation in farms. We suggest that
      the existing levels of heterozygosity among our thalli is not sufficient to
      detect any significant effect of genetic diversity on growth or productivity in
      Metri bay, our experimental site located close to the city of Puerto Montt,
      during summer under nitrogen limiting conditions.

PMID- 30222863
TI  - Overcoming the "Holy Hush": A Qualitative Examination of Protestant Christian
      Leaders' Responses to Intimate Partner Violence.
AB  - Described as a "holy hush," past research has noted a general silence about and
      reluctance to address intimate partner violence (IPV) in religious congregations.
      To explore this, we interviewed 20 Protestant Christian religious leaders about
      how they understood and responded to IPV. Based on a thematic content analysis,
      our study revealed some of the challenges, tensions, and complexities that may be
      barriers to leaders speaking about and responding to IPV, and also the ways
      religious leaders in our sample attempted to overcome these challenges. For
      example, results revealed religious leaders understood violence on a gradation
      from less to more severe, and linked a need for and type of response to the level
      of violence. Throughout, religious leaders expressed a tension between their
      leadership role and responding to IPV. Furthermore, religious leaders
      acknowledged their need for greater training and connections to service
      providers, however, they reported not currently being connected to other IPV
      resources or organizations in the community. We discuss how the findings
      illuminate challenges and tensions for religious leaders in responding to IPV and
      how some leaders in this study were navigating these tensions to respond. We also
      discuss how findings may inform future research and the development of trainings
      and protocols for religious leaders and congregations on responding to IPV,
      promoting survivor safety, and fostering a greater understanding of IPV.
      Implications for collaboration with other community-based IPV organizations are
      also discussed.

PMID- 30222864
TI  - Recommendations on the use of magnetic resonance imaging for collaborative
      multicenter studies in PSC.
AB  - Recently, the MRI working group of the International PSC Study Group (IPSCSG) has
      published a position statement on the use of MRI regarding diagnosis and follow
      up of PSC patients. These guidelines are intended for use by physicians in daily
      clinical routine. In addition, the group has outlined several areas of research,
      which need to be addressed in the near future. As PSC is a rare disease with the
      clinical outcome being determined by the development of end-stage liver disease
      and hepatobiliary malignancy. This article is protected by copyright. All rights
      reserved.

PMID- 30222866
TI  - Community Health Workers and Social Proximity: Implementation of a Parenting
      Program in Urban Poverty.
AB  - Community health workers (CHWs) offer a potential means through which to mitigate
      many of the barriers to mental health services faced by minority youth and their
      families. The primary aim of the present study was to better understand a core
      feature of CHWs: their shared community membership with the population served, or
      social proximity. We conducted qualitative semi-structured interviews with 16
      CHWs implementing a school-based early intervention program in Latino and African
      American communities of urban poverty. The program promoted child and
      parent/caregiver engagement in schooling as a protective factor for children's
      mental health. Thematic analyses revealed three main themes defining social
      proximity: (a) experiences of parenthood or caring for children, (b) familiarity
      with and understanding of culture, and (c) experiences of life hardships and
      struggles. Additionally, the process of relating with parents/caregivers through
      shared experiences was the main theme to describe how CHWs leveraged their social
      proximity. CHWs' accounts illustrated how their experience of social proximity to
      the population served was central to how they engaged parents/caregivers in
      services, highlighting the importance of supporting and promoting CHWs' natural
      traits and lived experiences.

PMID- 30222865
TI  - Severe hemolytic disease of the fetus and newborn due to allo-anti-D in a patient
      with a partial DEL phenotype arising from the variant allele described as
      RHD*148+1T (RHD*01EL.31).
AB  - BACKGROUND: RhD DEL variants may show complete or partial expression of RhD
      epitopes. There have been only rare reports of anti-D causing hemolytic disease
      of the fetus and newborn (HDFN) in this context. We report a case of severe HDFN
      associated with a recently described DEL variant. CASE REPORT: A multiparous
      woman presented with an allo-anti-D and showed incongruent phenotyping and
      genotyping results on initial study. Further investigations identified the RHD
      mutation, defined as RHD*148+1T and named RHD*01EL.31, which had been previously
      associated with a DEL phenotype. Extended RhD phenotyping by adsorption-elution
      showed that there was reactivity with four of nine monoclonal anti-D antibodies,
      suggesting a partial DEL phenotype. The first child showed no clinical evidence
      of HDFN, although the cord direct antiglobulin test was positive. The second
      child developed fetal anemia treated with intrauterine transfusion, and neonatal
      hyperbilirubinemia requiring exchange transfusion. CONCLUSION: The RHD allele,
      RHD*148+1T, results in a partial Del phenotype, and the anti-D formed in pregnant
      women with this phenotype is capable of causing severe HDFN.

PMID- 30222867
TI  - Investigation of the variable In(Lu) phenotype caused by KLF1 variants.
AB  - INTRODUCTION: KLF1 is an essential transcriptional activator that drives
      erythropoiesis. KLF1 variants can result in the Inhibitor of Lutheran, or In(Lu),
      phenotype where red blood cells (RBCs) have reduced BCAM (LU) and CD44 (IN).
      Other RBC surface molecules also have changed expression; however, there is
      controversy in the literature regarding which are truly impacted. We aimed to
      investigate KLF1 variants in the Australian population. STUDY DESIGN AND METHODS:
      In(Lu) samples were sourced through screening and through the RBC reference
      laboratory. Blood donor samples (8036) were screened to identify weakened/absent
      Lub antigen. Samples were genotyped by massively parallel sequencing, while
      surface carbohydrates and blood group molecules were assessed by flow cytometry.
      Hemoglobin (Hb) types were analyzed by high-performance liquid chromatography.
      RESULTS: Four of 8036 donors were identified to be In(Lu), and two previously
      identified In(Lu) samples were provided from the RBC reference laboratory. Five
      different KLF1 variants were identified; two were novel: c.954G>C/p.Trp318Cys and
      c.421C>T/p.Arg141*. BCAM and CD44 were reduced in all samples, consistent with
      previous reports. As a group, In(Lu) RBCs had reduced CD35 (KN), ICAM4 (LW), and
      CD147 (OK), and demonstrated increased binding of lectins ECA and SNAI. One
      In(Lu) sample had elevated HbF and another elevated HbA2. CONCLUSION: Different
      KLF1 variants may potentially produce variable phenotypes. A framework for
      investigating KLF1 variants and their phenotypic impact has been provided. In the
      future, given available international databases, further testing algorithms (as
      advocated here) will allow for correlation of phenotype with genotype and
      therefore accurately document this variability between KLF1 variants.

PMID- 30222868
TI  - Trajectories of Posttraumatic Stress and Depression in Police and Community
      Members Following the Violence during Civil Unrest in Ferguson, Missouri.
AB  - Longitudinal research following discreet traumatic events reveals distinct
      symptom trajectories in untreated survivors of trauma. Trajectories within
      communities exposed to shared, prolonged violence involving subgroups differing
      in perspectives, and roles during the event have not been studied. This study
      examined trajectories of posttraumatic stress (PTS) and depressive symptoms
      secondary to exposure to violence during civil unrest in citizens (n = 311) and
      law enforcement (n = 255) over 1.5 years following exposure. Latent class growth
      modeling was used to examine trajectories of PTS and depressive symptoms. Four
      class quadratic solutions for both PTS and depressive symptoms demonstrated best
      fit. Similar patterns emerged for such that most participants were classified as
      resistant (57% and 67%, respectively), followed by resilience (23.8% and 17.2%),
      chronic (12.6% and 12.0%), and worsening (6.1% and 4.4%). When all predictors
      were entered in a single model, race, and membership in citizen or law
      enforcement groups did not distinguish trajectories of recovery. Higher income
      and social support emerged as consistent protective factors against PTS and
      depressive symptoms, while trauma history emerged as a risk factor for PTS. Women
      were more at risk for depressive symptoms only. Implications for improving
      police/civilian relations in Ferguson, Missouri, and other communities are
      discussed.

PMID- 30222869
TI  - Posttransfusion purpura with antibodies against human platelet antigen-4a
      following checkpoint inhibitor therapy: a case report and review of the
      literature.
AB  - BACKGROUND: Posttransfusion purpura (PTP) is a rare condition characterized by
      severe thrombocytopenia following receipt of blood products. Most reported PTP
      cases involve alloantibodies directed against human platelet antigen (HPA)-1a. We
      present a case of PTP-mediated severe thrombocytopenia associated with
      alloantibodies directed against HPA-4a in the setting of combination checkpoint
      inhibitor therapy. CASE REPORT: A 62-year-old woman with rectal melanoma that
      progressed on combination checkpoint inhibitors (ipilimumab and nivolumab) was
      admitted for abdominoperineal resection. She received multiple blood products
      during surgery, and between the sixth and eighth days post-surgery her platelet
      (PLT) count decreased from 126 * 109 /L to a nadir of 1 * 109 /L. She received
      intravenous immunoglobulin (IVIG), steroids, and romiplostim with eventual
      recovery of her PLT count to 50 * 109 /L 20 days after surgery. She tested
      positive for anti-HPA-4a and was shown not to express HPA-4a, confirming a
      diagnosis of PTP. CONCLUSION: Alloantibodies strongly reactive to HPA-4a were
      detected in this patient who received multiple blood products during
      abdominoperineal resection surgery. Her thrombocytopenia improved with prompt
      administration of IVIG, steroids, and romiplostim. PTP must always be considered
      in patients with acute severe thrombocytopenia after receipt of blood products,
      and treatment should not be delayed while awaiting laboratory confirmation. To
      our knowledge, this is the second reported case of PTP with antibodies against
      HPA-4a.

PMID- 30222870
TI  - Sustainable antibullying program implementation: School profiles and predictors.
AB  - We examined the sustainability of the KiVa antibullying program in Finland from
      its nationwide roll-out in 2009 to 2016. Using latent class analyses, we
      identified four different patterns of implementation. The persistent schools
      (43%) maintained a high likelihood of participation throughout the study period.
      The awakened (14%) had a decreasing trend during the first years, but then
      increased the likelihood of program participation. The tail-offs (20%) decreased
      in the likelihood of participating after the third year, and the drop-offs (23%)
      already after the first year. The findings suggest that many schools need support
      during the initial years to launch and maintain the implementation of evidence
      based programs; yet a large proportion of schools manage to sustain the program
      implementation for several years. The logistic regression analyses showed that
      large schools persisted more likely than small schools. Lower initial level of
      victimization was also related to the sustainability of the program. Finally,
      persistent program participation was predicted by several school-level actions
      during the initial years of implementing the program. These results imply that
      the sustainability of evidence-based programs could be enhanced by supporting and
      guiding schools when setting up the program during the initial implementation.

PMID- 30222871
TI  - Fear of blood draw is associated with inflated expectations of faint and prefaint
      reactions to blood donation.
AB  - BACKGROUND: Although the risk of fainting and prefaint reactions (e.g.,
      dizziness, lightheadedness) is low during blood donation, there is evidence that
      this risk remains a concern for many donors. This study sought to measure
      perceived risk for such reactions within the general population and to relate
      perceived risk to individual reports of fear of having blood drawn. STUDY DESIGN
      AND METHODS: A sample of 1019 men and women (52.2% male; mean +/- SD age, 37.2 +/
      12.3 years; range, 18-80 years) completed an anonymous online survey that
      included questions that asked about their 1) estimation of the frequency of faint
      and prefaint symptoms experienced by blood donors and 2) fear of having blood
      drawn. RESULTS: Survey respondents overestimated the risk of both faint and
      prefaint reactions to blood donation, with estimates of fainting risk being more
      than 20 times the actual risk. Further, the perceived risk of both faint
      reactions (F(4,1008) = 25.88, p < 0.001) and prefaint reactions (F(4,1008) =
      17.37, p < 0.001) was higher among those who reported greater fear of having
      blood drawn. CONCLUSION: The general public has inflated expectations of the risk
      for faint and prefaint reactions to blood donation, suggesting that efforts to
      educate prospective donors with accurate information may help to reduce this
      relatively common concern.

PMID- 30222873
TI  - Subtyping, phenotyping or endotyping rosacea: how can we improve disease
      understanding and patient care?

PMID- 30222874
TI  - Multifocal anaplastic large cell lymphoma - insight into its biology and
      treatment.

PMID- 30222875
TI  - Image Gallery: Amyloidoma secondary to insulin injection.

PMID- 30222876
TI  - Corrigendum.

PMID- 30222877
TI  - The perceived promise of p19 inhibitors.

PMID- 30222879
TI  - Improvements in quality of life and work productivity make omalizumab cost
      effective for the treatment of chronic spontaneous urticaria.

PMID- 30222880
TI  - Highlighting the need for prospective randomized studies on the management of
      dysplastic naevi.

PMID- 30222881
TI  - Early evidence for opposing effects of full versus fragmented adiponectin on
      melanogenesis in human epidermal melanocytes.

PMID- 30222883
TI  - Are adolescents with atopic eczema really undertreated in real life?

PMID- 30222884
TI  - Minimizing differences in treatment: expert- and evidence-based guidelines for
      propranolol treatment of infantile haemangiomas in the U.K. and beyond.

PMID- 30222885
TI  - Image Gallery: Capillaroscopy for noninvasive scabies diagnosis.

PMID- 30222887
TI  - Interventional management of hyperhidrosis in secondary care: where do we go from
      here?

PMID- 30222886
TI  - Image Gallery: Wyburn-Mason syndrome with a chronic wound.

PMID- 30222888
TI  - Programmed death-1 blockade for multiple basal cell carcinomas: clearing the
      field systemically?

PMID- 30222889
TI  - Core outcome sets in dermatology: next steps.

PMID- 30222890
TI  - Multiple facets of desmoglein 1 mutations.

PMID- 30222891
TI  - Hyaluronan is a key regulator of skin homeostasis and wound healing.

PMID- 30222892
TI  - New therapeutics for itch in dermatomyositis.

PMID- 30222893
TI  - Effects of environmental skin stressors on filaggrin degradation products:
      importance for eczema.

PMID- 30222894
TI  - Biologics are too complicated to duplicate: should we be worried about
      biosimilars?

PMID- 30222895
TI  - Increased healthcare costs for filaggrin-related eczema and asthma: hope for
      targeted management and prevention.

PMID- 30222896
TI  - Image Gallery: Expression of CD30 in orf infection presenting as a giant
      targetoid erythematous nodule.

PMID- 30222897
TI  - Review and case report demonstrate that spontaneous spinal epidural abscesses are
      rare but dangerous in childhood.
AB  - AIM: A spinal epidural abscess (SEA) is a rare paediatric bacterial infection,
      with possible devastating neurological sequelae. We explored localisation in the
      cervical segment, which is unusual, but more dangerous, than other SEAs. METHODS:
      We describe 22 cases (12 male) of paediatric SEAs without risk factors: 21 from a
      literature search from 2000 to 2017 and a 30-month-old boy with a spontaneous
      cervical SEA due to Group A Streptococcus. RESULTS: The average age was eight
      years and the symptoms were mainly fever, back pain and motor deficit, with an
      aetiological diagnosis in 68%. Methicillin-sensitive Staphylococcus aureus was
      isolated in six patients, methicillin-resistant Staphylococcus aureus in two,
      Staphylococcus aureus with unknown susceptibility patterns in three and Group A
      Streptococcus in four. All patients underwent gadolinium-enhanced magnetic
      resonance imaging and most abscesses were localised in the thoracic and lumbar
      areas. More than half (59%) underwent surgery to remove pus and granulation
      tissue and nine were just treated with antimicrobial therapy for an average of
      5.3 weeks. Most patients had good outcomes. CONCLUSION: SEAs were underestimated
      in children due to the rarity and spectrum of differential diagnoses. Timely
      diagnosis, immediate antibiotics, spinal magnetic resonance imaging and prompt
      neurosurgical consultations were essential for favourable outcomes.

PMID- 30222898
TI  - Serum concentrations of C-reactive protein in healthy term-born Norwegian infants
      48-72 hours after birth.
AB  - AIM: To determine serum C-reactive protein (CRP) concentrations in healthy term
      born infants shortly after birth. METHODS: We sampled blood from 182 infants
      along with the routine neonatal screening programme at 48-72 hours of age from
      consecutively recruited healthy infants without signs of infection and a
      gestational age (GA) of at least 37 weeks. The blood was stored at minus 20
      degrees C until analysis in one assay after the end of the study. RESULTS: The
      CRP levels were positively skewed. The median concentration was 5.0 mg/L, 48.9%
      of the neonates had values <5.0 mg/L, 19.8% >=10.0 mg/L, 7.1% >=20.0 mg/L and
      1.1% (2 neonates) >30 mg/L. The CRP level was positively related to GA and
      duration of labour, slightly higher in boys than girls and after vaginal compared
      to Caesarean delivery. CONCLUSION: In healthy neonates born at term, the CRP
      concentrations did not vary substantially with various common perinatal clinical
      conditions, and levels above 30 mg/L were uncommon at two to three days of age.

PMID- 30222899
TI  - The immune checkpoint CD96 defines a distinct lymphocyte phenotype and is highly
      expressed on tumor-infiltrating T cells.
AB  - CD96 has recently been shown to be a potent immune checkpoint molecule in mice,
      but a similar role in humans is not known. In this study, we provide a detailed
      map of CD96 expression across human lymphocyte lineages, the kinetics of CD96
      regulation on T-cell activation and co-expression with other conventional and
      emerging immune checkpoint molecules. We show that CD96 is predominantly
      expressed by T cells and has a unique lymphocyte expression profile. CD96high T
      cells exhibited distinct effector functions on activation. Of note, CD96
      expression was highly correlated with T-cell markers in primary and metastatic
      human tumors and was elevated on antigen-experienced T cells and tumor
      infiltrating lymphocytes. Collectively, these data demonstrate that CD96 may be a
      promising immune checkpoint to enhance T-cell function against human cancer and
      infectious disease.

PMID- 30222900
TI  - Granular cell astrocytoma: an aggressive IDH-wildtype diffuse glioma with
      molecular genetic features of primary glioblastoma.
AB  - Granular cell astrocytoma (GCA) is a rare adult infiltrating glioma subtype. We
      studied a series of 39 GCAs. Median age of presentation was 57.8 years and most
      cases developed in the frontal or temporal lobes. Tumors included grade II (n =
      14), grade III (n = 11), and grade IV (n = 14) by WHO criteria. Granular cell
      morphology was diffuse in 31 (79%) cases and partial in eight (21%).
      Immunohistochemistry showed frequent positivity for GFAP (28 of 31), OLIG2 (16 of
      16), and CD68 (27 of 30), but HAM56, CD163, and IBA-1 histiocytic markers were
      all negative (22 of 22). IDH1(R132H) was negative in all the cases tested (16 of
      16), while ATRX expression was retained (12 of 12). Cytogenetics demonstrated
      monosomy 10 (6 of 6) cases, +7 in 4 (of 6), -13q in 4 of 6, and -14 in 4 of 6.
      Next-generation sequencing demonstrated mutations in PTEN/PIK3 genes in 6/13
      (46%), NF1 in 3 of 10 (30%), TP53 in 3 of 13 (23%), PALB2 in 3 of 10 (30%), STAG2
      in 3 of 10 (30%), EGFR mutation/amplification in 3 of 13 (23%), and AR in 2 of 10
      (20%). CDKN2A/B deletion was identified in 5 of 13 (30%) cases (homozygous
      deletion in 4). The TERT C228T mutation was identified in 9 of 13 (69%). No
      mutations were encountered in IDH1, IDH2, CIC, FUBP1, H3F3A, BRAF or ATRX genes.
      The mean overall survival was 11.3 months. Patients >60 years old at diagnosis
      had a worse survival than patients <60 years (P = 0.001). There were no
      statistically significant differences in survival by WHO grade, extent of
      granular cell change, sex or MIB-1 (P > 0.05). GCA is a variant of IDH-wildtype
      diffuse glioma with aggressive behavior irrespective of grade and extent of
      granular cell morphology, and with molecular genetic features corresponding to
      primary glioblastoma.

PMID- 30222901
TI  - Bioprosthetic pulmonary valve endocarditis: Incidence, risk factors, and clinical
      outcomes.
AB  - BACKGROUND: Pulmonary valve replacement (PVR) is a common operation in patients
      with congenital heart disease (CHD). As survival with CHD improves, infective
      endocarditis (IE) is a growing complication after PVR. The aim of this study was
      to assess the incidence, risk factors, and clinical outcomes of IE after surgical
      PVR in patients with CHD at our institution. METHODS: Retrospective analysis of
      all cases of surgical PVR performed at Children's Hospital of Wisconsin between
      1975 and 2016 was performed. All cases of IE after PVR were identified and
      clinical and imaging data were obtained by review of medical records. RESULTS:
      Out of 924 surgical PVRs, there were 19 (2%) cases of IE. The incidence of IE
      after surgical PVR was 333 cases per 100,000 person-years. The median age at
      diagnosis of IE was 21 years (range = 1.2-34 years) and the median time from PVR
      to diagnosis of IE was 9.4 years. The overall freedom from IE after PVR was
      99.1%, 96.9%, and 93.4%, at 5, 10, and 15 years, respectively. There was no
      significant difference in freedom from IE based on valve type, including bovine
      jugular vein grafts. Patients with IE were more likely to have had a history of
      multiple PVRs, while length of follow-up after PVR, age at time of PVR, and
      gender were not significant risk factors. Eleven (58%) cases of IE required
      surgical intervention, while 8 (42%) were successfully treated with intravenous
      antibiotics alone. There were no deaths and no recurrences of IE after treatment.
      CONCLUSION: The overall risk for IE after PVR is low. There was no association
      between age or type of pulmonary valve and risk of IE. The majority of cases
      require surgical intervention, but in general the outcomes of IE after PVR are
      good with low mortality and risk of recurrence.

PMID- 30222902
TI  - Donor-derived Philadelphia chromosome-positive B cell lymphoblastic leukemia
      presenting with renal allograft involvement in the first year posttransplant.

PMID- 30222903
TI  - Post-intestine transplant graft-vs-host disease associated with inclusion of a
      liver graft and with a high mortality risk.
AB  - INTRODUCTION: This study reports the incidence, anatomic location, and outcomes
      of graft-vs-host disease (GVHD) at a single active intestine transplant center.
      METHODS: Records were reviewed for all patients receiving an intestine transplant
      from 2003 to 2015. Pathology reports and pharmacy records were reviewed to
      establish the diagnosis, location, and therapeutic interventions for GVHD.
      RESULTS: A total of 236 intestine transplants were performed during the study
      period, with 37 patients (16%) developing GVHD. The median time to onset of
      disease was 83 days, with 89% of affected patients diagnosed in the first year
      post-transplant. Mortality for affected patients was 54% in the 1 year after GVHD
      diagnosis. Skin lesions were the most common manifestation of GVHD. Other sites
      of disease included lungs, bone marrow, oral mucosa, large intestine, and brain.
      The incidence of GVHD was 16% in adult patients, and slightly lower in pediatric
      recipients (13%). In adults, increasing graft volume (isolated vs multi-organ)
      and liver inclusion were associated with increasing risk of GVHD, though this was
      not seen in pediatric patients. CONCLUSION: Overall, 16% of intestine transplant
      recipients developed GVHD. GVHD is associated with high mortality, and disease in
      the lungs, brain, and bone marrow was universally fatal.

PMID- 30222904
TI  - mGlu1 tonically regulates levels of calcium-permeable AMPA receptors in cultured
      nucleus accumbens neurons through retinoic acid signaling and protein
      translation.
AB  - In several brain regions, ongoing metabotropic glutamate receptor 1 (mGlu1)
      transmission has been shown to tonically suppress synaptic levels of Ca2+ 
      permeable AMPA receptors (CP-AMPARs) while pharmacological activation of mGlu1
      removes CP-AMPARs from these synapses. Consistent with this, we previously showed
      in nucleus accumbens (NAc) medium spiny neurons (MSNs) that reduced mGlu1 tone
      enables and mGlu1 positive allosteric modulation reverses the elevation of CP
      AMPAR levels in the NAc that underlies enhanced cocaine craving in the
      "incubation of craving" rat model of addiction. To better understand mGlu1/CP
      AMPAR interactions, we used a NAc/prefrontal cortex co-culture system in which
      NAc MSNs express high CP-AMPAR levels, providing an in vitro model for NAc MSNs
      after the incubation of cocaine craving. The non-specific group I orthosteric
      agonist dihydroxyphenylglycine (10 min) decreased cell surface GluA1 but not
      GluA2, indicating CP-AMPAR internalization. This was prevented by mGlu1
      (LY367385) or mGlu5 (MTEP) blockade. However, a selective role for mGlu1 emerged
      in studies of long-term antagonist treatment. Thus, LY367385 (24 hr) increased
      surface GluA1 without affecting GluA2, whereas MTEP (24 hr) had no effect. In
      hippocampal neurons, scaling up of CP-AMPARs can occur through a mechanism
      requiring retinoic acid (RA) signaling and new GluA1 synthesis. Consistent with
      this, the LY367385-induced increase in surface GluA1 was blocked by anisomycin
      (translation inhibitor) or 4-(diethylamino)-benzaldehyde (RA synthesis
      inhibitor). Thus, mGlu1 transmission tonically suppresses cell surface CP-AMPAR
      levels, and decreasing mGlu1 tone increases surface CP-AMPARs via RA signaling
      and protein translation. These results identify a novel mechanism for homeostatic
      plasticity in NAc MSNs.

PMID- 30222905
TI  - A fatal diarrhoea outbreak in farm-raised Deinagkistrodon acutus in China is
      newly linked to potentially zoonotic Aeromonas hydrophila.
AB  - Deinagkistrodon acutus is a venomous pit viper commonly used in traditional
      Chinese medicine; farming these snakes has become a major industry. In 2017, an
      outbreak of fatal diarrhoea among farm-raised D. acutus in Hunan Province caused
      the deaths of 5,600 snakes within 3 weeks. We isolated a brand-new sequence type
      of Aeromonas hydrophila (ST516) from lesions and confirmed that this bacterium
      was the causal agent of the outbreak. Snakes infected with the bacterium in the
      laboratory showed similar clinical symptoms to those of snakes in the original
      outbreak. We also tested bacterial virulence in Kunming mice to examine the
      likelihood of zoonosis. Isolates were pathogenic to mice, causing diarrhoea
      within 4 hr post-challenge, which indicates that the bacterium can potentially
      infect mammals. Environmental analysis showed that polluted spring water likely
      caused the diarrhoea in snakes. This study is the first to report on a large
      scale outbreak of fatal diarrhoea in farm-raised snakes, originating in a
      pathogen that can infect mammals. These results should raise awareness regarding
      potential anthropozoonosis among poikilotherms, mammals, and humans; appropriate
      prevention or control methods should be developed.

PMID- 30222907
TI  - Content of university alcohol policies in New South Wales, Australia.
AB  - ISSUE ADDRESSED: This study aimed to develop a working checklist for university
      alcohol policies and apply this checklist to current policies in universities in
      New South Wales (NSW), Australia. METHODS: We developed a working checklist of
      possible university alcohol policy approaches, drawn from the World Health
      Organization's alcohol policy recommendations, university alcohol policy research
      from the United States and norms and expectations currently incorporated in
      Australian university alcohol policies. We then conducted a content analysis of
      university alcohol policies in NSW, Australia, based on this checklist. All NSW
      university websites were searched for any policies or guidelines related to
      alcohol. The content of each policy or guideline was assessed in terms of whether
      it satisfied the various components of the checklist. RESULTS: All 11
      universities in NSW have an alcohol policy, and these policies are readily
      available and accessible online. There were two main themes identified in the
      aims across documents: maximising health and safety of individuals and protecting
      the university as an institutional entity. Inclusiveness and safety were the
      predominant themes that satisfied policy content. No document incorporated
      methods for monitoring/evaluating policy impact. CONCLUSIONS: University alcohol
      policies that incorporated both individual-level and population-based approaches
      to alcohol harm reduction were more likely to score higher on the checklist.
      However, this analysis highlighted many opportunities to strengthen policies by
      increasing their comprehensiveness and incorporating means to evaluate their
      effectiveness. SO WHAT?: We present a working checklist that can be used for
      future research and policy development, regarding university alcohol policies and
      guidelines.

PMID- 30222906
TI  - A mixed-methods study of the management of hearing loss associated with otitis
      media with effusion in children with Down syndrome.
AB  - OBJECTIVES: To scope current service provision across England for management of
      otitis media with effusion and hearing loss in children with Down syndrome; to
      explore professional decision-making about managing otitis media with effusion
      and hearing loss; and to explore patient and public views on the direction of
      future research. DESIGN: Mixed methods including a service evaluation of NHS
      clinical practice through a structured telephone survey; a qualitative study of
      professional decision-making with in-depth interviews collected and analysed
      using grounded theory methods; patient/public involvement consultations.
      PARTICIPANTS: Twenty-one audiology services in England took part in the
      evaluation; 10 professionals participated in the qualitative study; 21 family
      members, 10 adults with Down syndrome and representatives from two charities
      contributed to the consultations. RESULTS: There was variation across services in
      the frequency of routine hearing surveillance, approaches to managing conductive
      hearing loss in infancy and provision of hearing aids and grommets. There was
      variation in how professionals describe their decision-making, reflecting
      individual treatment preferences, differing approaches to professional remit and
      institutional factors. The consultations identified that research should focus on
      improving practical support for managing the condition and supporting decision
      making about interventions. CONCLUSIONS: There is system-level variation in the
      provision of services and individual-level variation in how professionals make
      clinical decisions. As a consequence, there is inequity of access to hearing
      health care for children with Down syndrome. Future research should focus on
      developing core outcomes for research and care, and on improving decision support
      for families.

PMID- 30222908
TI  - Detection of high-grade dysplasia, carcinoma in situ and squamous cell carcinoma
      in the upper aerodigestive tract: Recommendations for optimal use and
      interpretation of narrow-band imaging.
AB  - OBJECTIVES: The primary goal was to study the diagnostic potential of narrow-band
      imaging (NBI), and the secondary goal was to evaluate the most common mistakes
      when using and interpreting NBI. DESIGN: Retrospective study. SETTING: University
      Medical Center Groningen, tertiary referral hospital, the Netherlands.
      PARTICIPANTS: Three hundred and seventy patients who underwent rigid endoscopy of
      the upper aerodigestive tract. Two observers assessed all lesions. Twelve
      observers assessed a selection of 100 lesions. All observers were provided with
      both white light imaging and NBI. MAIN OUTCOME MEASURES: Sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      accuracy and reasons for insufficient photograph quality. RESULTS: When using
      NBI, the sensitivity, specificity, PPV, NPV and accuracy for detecting invasive
      carcinoma, carcinoma in situ or high-grade dysplasia were 92%, 68%, 61%, 94% and
      77%, respectively. In multiple-observer analysis, values were 76%, 58%, 53%, 83%
      and 65% with the evaluation strictly based on type V patterns of Ni's
      classification, vs 83%, 68%, 64%, 85% and 74% when evaluation was also based on
      lesion-specific clinical characteristics. Lesions that caused misinterpretations
      were leukoplakia, papillomas and mucosal lesions after irradiation. In total, 185
      photographs were assessed to be of suboptimal quality due to blurring (36%),
      bleeding (6%), insufficient zooming (15%) and/or insufficient lighting (17%).
      CONCLUSION: NBI is a relatively reliable screening method for detecting
      malignancy. Evaluation based on Ni's classification alone is not sufficient. To
      optimise NBI photograph quality, we recommend sufficient zooming and prevention
      of bleeding, blurring and inadequate lighting.

PMID- 30222909
TI  - Triel-Bonded Complexes between TrR3 (Tr=B, Al, Ga; R=H, F, Cl, Br, CH3 ) and
      Pyrazine.
AB  - Complexes between TrR3 (Tr=B, Al, Ga; R=H, F, Cl, Br, CH3 ) molecules and
      pyrazine have been characterized at the MP2 and CCSD(T) levels of theory. The
      adducts can be grouped according to the type of molecular arrangement. The first
      situation places the Tr atom in the plane of the pyrazine ring and contains a
      triel bond to the N lone pair. For the boron complexes the orbital interaction
      energy is almost equal to the electrostatic component, while the former is only
      half the latter for Tr=Al and Ga. The two monomers are stacked above one another
      in the second configuration, which depends to a greater degree upon orbital
      interaction and dispersion. The former complexes are more strongly bonded than
      the latter. Interaction energies (Eint ) for the stronger complexes vary between 
      50 and -20 kcal/mol for BBr3 and Ga(CH3 )3 paired respectively with pyrazine.
      Eint is much smaller for the stacked configurations, ranging from -8 for GaF3 to 
      1.4 kcal/mol for BF3 . The value of the maximum of the electrostatic potential
      correlates poorly with Eint , attributed in part to monomer distortions upon
      complexation.

PMID- 30222910
TI  - Fluorine-Free Water-in-Salt Electrolyte for Green and Low-Cost Aqueous Sodium-Ion
      Batteries.
AB  - The highly concentrated "water-in-salt" electrolyte (WiSE) containing sodium
      acetate and potassium acetate demonstrates surprising performance (specific
      capacity of 37 mA h-1  g-1 at the 5th cycle and average discharge voltage of 0.82
      V) in aqueous sodium-ion batteries (SIBs) based on Na2 MnFe(CN)6 and NaTi2 (PO4
      )3 . The fluorine-free electrolyte offers a wide electrochemical stability window
      and compatibility with Al current collector. The electrolyte, current collector,
      and the electrode materials based on abundant elements make the proposed battery
      chemistry safe, low-cost, and environmentally friendly.

PMID- 30222911
TI  - Personal factors associated with the attitudes of nurses towards patients with
      obesity: a literature review.
AB  - This literature review explores the association between body mass index and self
      esteem in nurses, alongside their attitudes towards patients who have obesity.
      These variables have either previously been linked to weight bias, or with
      prejudice more generally, but findings in this context are inconclusive. Searches
      were conducted through Psychology Cross Search, PubMed, Web of Science, Proquest
      Allied Health Professionals and Google Scholar. Ten studies met the inclusion
      criteria and were tabulated and critiqued using appropriate appraisal tools. The
      literature covered a time span of over 30 years with the type and quality of
      study methodologies varying. Research was rarely underpinned by theory. As such,
      no consensus was reached in drawing together the findings but the direction of
      future research needed to address these issues is discussed. Further research
      should focus on developing the literature using an appropriate theoretical
      underpinning in order to better understand the research that has begun further
      afield.

PMID- 30222912
TI  - Pest suppression in cultivar mixtures is influenced by neighbor-specific plant
      plant communication.
AB  - Increased plant genotypic diversity in crop fields can promote ecosystem services
      including pest control, but understanding of mechanisms behind herbivore
      population responses to cultivar mixtures is limited. We studied aphid settling
      on barley plants exposed to volatiles from different cultivars, aphid population
      development in monocultures and two-cultivar mixtures, and differences in
      volatile composition between studied cultivars. Aphid responses to one cultivar
      in a mixture were neighbor-specific and this was more important for pest
      suppression than the overall mixture effect, aphid colonization patterns, or
      natural enemy abundance. Aphid populations decreased most in a mixture where both
      cultivars showed a reduced aphid-plant acceptance after reciprocal volatile
      exposure in the laboratory, and reduced population growth compared to
      monocultures in the field. Our findings suggest that herbivore population
      responses to crop genotypic diversity can depend on plant-plant volatile
      interactions, which can lead to changes in herbivore response to individual
      cultivars in a mixture, resulting in slower population growth. The impact of
      plant-plant interaction through volatiles on associated herbivore species is
      rarely considered, but improved understanding of these mechanisms would advance
      our understanding of the ecological consequences of biodiversity and guide
      development of sustainable agricultural practices. Combining cultivars in
      mixtures based on how they interact with each other is a promising strategy for
      sustainable pest management.

PMID- 30222913
TI  - Thirty-day recurrence after ischemic stroke or TIA.
AB  - BACKGROUND: Incidence of recurrent stroke is highest within 30 days after the
      initial ischemic stroke (IS) or TIA, but knowledge about early recurrence is
      lacking. We aimed to identify etiological groups with highest risk of early
      recurrence and assess how the TOAST classification identified index stroke
      etiology. METHODS: Medical records of 1874 IS and TIA patients in the Bergen
      NORSTROKE registry were retrospectively reviewed for identification of recurrent
      IS or TIA within 30 days after index IS or TIA. Stroke etiology was determined by
      review of electronical medical journals. Logistic regression was used to
      calculate odds ratios (OR) for 30-day recurrence. RESULTS: Thirty-three patients
      (1.8%) were readmitted with recurrent IS or TIA within 30 days after index
      stroke. By using TOAST, 12 patients were initially classified with stroke of
      unknown etiology (SUE). Etiologies behind recurrent IS or TIA were after the
      recurrent episode identified as extracranial large artery atherosclerosis (LAA)
      in 14 patients (42.4%), intracranial arterial pathology in seven patients
      (21.2%), active malignancy in six patients (18.2%), and cardio embolism in four
      patients (12.1%). Small vessel occlusion and SUE were the causes in one patient
      each. Logistic regression showed that patients with stroke of other determined
      etiology (SOE) and LAA had increased risk of 30-day recurrence (OR = 9.72, 95% CI
      1.84-51.3, p < 0.01 and OR = 4.36, 95% CI 2.01-9.47, p < 0.01, respectively).
      CONCLUSION: Patients with LAA and SOE had increased risk of recurrent IS or TIA
      within 30 days. TOAST was inadequate at identifying exact etiologies behind
      recurrent stroke at index event.

PMID- 30222914
TI  - Foot-and-mouth disease outbreaks due to an exotic virus serotype A lineage
      (A/AFRICA/G-IV) in Algeria in 2017.
AB  - This study describes the genetic characterization of serotype A viruses collected
      during outbreaks of foot-and-mouth disease (FMD) that occurred in Algeria in
      2017. These are the first reports of clinical cases due to this serotype in the
      country since 1977. One complete genomic sequence (comprising 8,119 nucleotides)
      and three additional near-complete genomic sequences were generated. Phylogenetic
      analyses demonstrated that these viruses were classified within the A/AFRICA/G-IV
      lineage, most closely related to viruses circulating in Nigeria between 2009 and
      2015. These unexpected results motivate further studies to define the precise
      pathways by which this viral lineage has been introduced into North Africa in
      order to understand risks of future disease incursions into the region.

PMID- 30222915
TI  - Results of the British Association of Urological Surgeons female stress urinary
      incontinence procedures outcomes audit 2014-2017.
AB  - OBJECTIVES: To analyse the results of the stress urinary incontinence (SUI) audit
      conducted by the British Association of Urological Surgeons (BAUS), and to
      present UK urologists' contemporary management of SUI. PATIENTS AND METHODS: The
      BAUS audit tool is an online resource, to which all UK urologists performing
      procedures for SUI are invited to submit data. The data entries for procedures
      performed during 2014-2016 were collated and analysed. RESULTS: Over the 3-year
      period analysed, 2 917 procedures were reported by 109 surgeons, with a median of
      20 procedures reported per surgeon. A total of 2 366 procedures (81.1%) were
      recorded as a primary surgery, with 548 procedures (18.8%) performed for
      recurrent SUI. Within the time period analysed, changes were noted in the
      frequency of all procedures performed, with a trend towards a reduction in the
      use of synthetic mid-urethral tapes, and a commensurate increase in the use of
      urethral bulking agents and autologous fascial slings. A total of 107 (3.9% of
      patients) peri-operative complications were recorded, with no association
      identified with patient age, BMI or surgeon volume. Follow-up data were available
      on 1 832 patients (62.8%) at a median of 100 days postoperatively. Reduced pad
      use was reported in 1 311 of patients (84.5%) with follow-up data available and
      86.3% reported a pad use of one or less per day. In all, 375 patients (85%)
      reported being satisfied or very satisfied with the outcome of their procedure at
      follow-up, although data entry for this domain was poor. De novo overactive
      bladder (OAB) symptoms were reported by 15.2% of patients (263/1 727), and this
      was the most commonly reported postoperative complication. For those reporting
      pre-existing OAB prior to their SUI surgery, 28.7% (307/1 069) of patients
      reported they got better after their procedure, whilst 61.9% (662/1 069) of
      patients reported no change and 9.4% of patients (100/1 069) got worse.
      CONCLUSIONS: This review identified that, despite urological surgeons undertaking
      a relatively low volume of procedures per year, SUI surgery by UK urologists is
      associated with excellent short-term surgeon- and patient-reported outcomes and
      low numbers of low grade complications. Complications do not appear to be
      associated with surgeon volume, nor do they appear higher in those undergoing
      mesh surgery. Shortfalls in data collection have been identified, and a longer
      follow-up period is required to comment adequately on long-term complications,
      such as chronic pain and tape extrusion/erosion rates.

PMID- 30222917
TI  - "Precision health" for high-need, high-cost patients.
AB  - It is increasingly clear that high-need, high-cost patients are not a homogenous
      group, but rather a diverse set of patients with varied circumstances and needs.
      Acting on this insight requires comprehensive data networks we have not
      traditionally had, and most analyses to date have focused primarily on claims
      data. We argue that making clinical and financial gains will require data-sharing
      networks that integrate clinical factors, genomic information, and social
      determinants from multiple health systems. Investing in these networks may allow
      us to better anticipate the unique needs of patients, conceptualize care models
      to meet those needs, and put targeted interventions into action.

PMID- 30222916
TI  - A randomized controlled trial of lorcaserin and lifestyle counselling for weight
      loss maintenance: changes in emotion- and stress-related eating, food cravings
      and appetite.
AB  - Anti-obesity medication may help people maintain diet-induced reductions in
      appetite. The present exploratory analysis assessed the effects of lorcaserin on
      changes at 24 weeks post-randomization in emotion- and stress-related eating,
      food cravings and other measures of appetite (i.e. binge eating, cognitive
      restraint, disinhibition, hunger, preoccupation with eating and fullness). The
      parent study investigated the efficacy of combined lorcaserin and behavioural
      treatment in facilitating weight loss maintenance (WLM) in 137 adults (mean age =
      46.1 years, 86.1% female, 68.6% black) who had lost >=5% of initial weight during
      a 14-week, low-calorie diet (LCD) run-in. Participants were randomly assigned to
      lorcaserin or placebo and were provided with group WLM counselling sessions.
      Emotion- and stress-related eating, food cravings and appetite were measured at
      the start of the LCD (week -14), randomization (0) and week 24. From
      randomization, lorcaserin-treated participants had significantly greater
      improvements in emotion- and stress-related eating compared to placebo-treated
      participants (P = 0.04). However, groups did not differ significantly after
      randomization in changes in the frequency of food cravings, binge eating or other
      measures of appetite (Ps > 0.05). Compared to placebo, lorcaserin may improve
      emotion- and stress-related eating.

PMID- 30222918
TI  - Food insecurity, healthcare utilization, and high cost: a longitudinal cohort
      study.
AB  - OBJECTIVES: Reducing utilization of high-cost healthcare services is a common
      population health goal. Food insecurity-limited access to nutritious food owing
      to cost-is associated with chronic disease, but its relationship with healthcare
      utilization is understudied. We tested whether food insecurity is associated with
      increased emergency department (ED) visits, hospitalizations, and related costs.
      STUDY DESIGN: Retrospective analysis of a nationally representative cohort.
      METHODS: Adults (>=18 years) completed a food insecurity assessment (using 10
      items derived from the US Department of Agriculture Household Food Security
      Module) in the 2011 National Health Interview Survey and were followed in the
      2012-2013 Medical Expenditures Panel Survey. Outcome measures were ED visits,
      hospitalizations, days hospitalized, and whether participants were in the top
      10%, 5%, or 2% of total healthcare expenditures. RESULTS: Of 11,781 participants,
      2056 (weighted percentage, 13.2%) were in food-insecure households. Food
      insecurity was associated with significantly more ED visits (incidence rate ratio
      [IRR], 1.47; 95% CI, 1.12-1.93), hospitalizations (IRR, 1.47; 95% CI, 1.14-1.88),
      and days hospitalized (IRR, 1.54; 95% CI, 1.06-2.24) after adjustment for
      demographics, education, income, health insurance, region, and rural residence.
      Food insecurity was also associated with increased odds of being in the top 10%
      (odds ratio [OR], 1.73; 95% CI, 1.31-2.27), 5% (OR, 2.53; 95% CI, 1.51-3.37), or
      2% (OR, 1.95; 95% CI, 1.09-3.49) of healthcare expenditures. CONCLUSIONS: Food
      insecurity is associated with higher healthcare use and costs, even accounting
      for other socioeconomic factors. Whether food insecurity interventions improve
      healthcare utilization and cost should be tested.

PMID- 30222919
TI  - Language barriers and LDL-C/SBP control among Latinos with diabetes.
AB  - OBJECTIVES: Language barriers in healthcare are associated with worse glycemic
      control among Latino patients with limited English proficiency and diabetes. We
      examined the association of patient-physician language concordance with lipid
      (low-density lipoprotein cholesterol [LDL-C]) and systolic blood pressure (SBP)
      control. STUDY DESIGN: Retrospective cohort study. METHODS: Data were obtained
      from a survey and the electronic health records of Latino and white patients with
      diabetes receiving care within 1 integrated health plan with interpreter services
      available. Limited English proficiency and patient-physician language concordance
      were defined by patient report. Outcomes were poor lipid control (LDL-C >100
      mg/dL) and poor SBP control (SBP >140 mm Hg). RESULTS: In total, 3463 Latino
      (2921 who spoke English and 542 who were limited English proficient [LEP]) and
      3896 English-speaking white patients participated. One-third of the patients had
      poor lipid control and one-fifth had poor SBP control. English-speaking white
      patients were slightly less likely to have poor lipid control than English
      speaking Latino patients, but the difference did not persist after adjustment for
      age and sex. Among Latinos, LEP patients were less likely to have poor lipid
      control than English-speaking patients (odds ratio, 0.71; 95% CI, 0.54-0.93),
      with no difference by LEP patient-physician language concordance. Poor SBP
      control did not differ by ethnicity, primary language, or patient-physician
      language concordance. CONCLUSIONS: We found no evidence that ethnicity or
      language barriers in healthcare were associated with poorer lipid or blood
      pressure control among Latino and white patients with diabetes receiving care in
      settings with professional interpreters.

PMID- 30222920
TI  - Hepatitis C care cascade among persons born 1945-1965: 3 medical centers.
AB  - OBJECTIVES: Effective screening, diagnosis, and treatment are needed to reduce
      chronic hepatitis C virus (HCV) infection-associated morbidity and mortality. In
      order to successfully increase HCV treatment, it is necessary to identify and
      understand gaps in linkage of antibody-positive patients with newly identified
      HCV to subsequent HCV RNA testing, clinical evaluation, and treatment. STUDY
      DESIGN: To estimate attainment of HCV care cascade steps among antibody-positive
      patients with newly identified HCV, we conducted chart reviews of patients with a
      new positive HCV antibody test at 3 academic medical centers participating in the
      Birth-Cohort Evaluation to Advance Screening and Testing of Hepatitis C (BEST-C)
      study. METHODS: We tracked receipt of RNA testing, clinical evaluation, treatment
      initiation, and treatment completion among individuals born between 1945 and 1965
      who were newly diagnosed as HCV antibody-positive between December 2012 and
      October 2015 at 3 BEST-C centers, predominantly from the participating medical
      centers' primary care practices and emergency departments. RESULTS: Of the 130
      HCV-seropositive individuals identified, 118 (91%) had an RNA or genotype test,
      75 (58%) were RNA-positive, 73 (56%) were linked to care, 22 (17% overall; 29%
      among RNA-positive) started treatment, and 21 (16%; 28% among RNA-positive)
      completed treatment. CONCLUSIONS: This analysis showed that although linkage to
      care was largely successful in the target birth cohort, the largest gap in the
      HCV care cascade was seen in initiating treatment. Greater emphasis on linking
      patients to clinical evaluation and treatment is necessary in order to achieve
      the public health benefits promised by birth-cohort testing.

PMID- 30222921
TI  - Health literacy, preventive health screening, and medication adherence behaviors
      of older African Americans at a PCMH.
AB  - OBJECTIVES: To determine the health literacy (HL) of older African Americans
      (AAs) and establish whether associations exist between HL and preventive health
      screening (PHS) behaviors, disease control (DC), and medication adherence (MA).
      STUDY DESIGN: A prospective study using a clustered sampling of older AAs.
      METHODS: A total of 99 older AAs seeking care at a patient-centered medical home
      were given the Newest Vital Sign (NVS), Short Test of Functional Health Literacy
      in Adults (STOFHLA), and Morisky Medication Adherence Scale (MMAS).
      Sociodemographic and clinical data were obtained. RESULTS: The group was 75.8%
      female, with means of 75 years of age, 12.7 years education, and 29.5 kg/m2 body
      mass index and good control over disease markers: For blood pressure, 62.6% had
      good control; for blood glucose, 82.8%; and for total lipids/cholesterol, 63.6%
      (high-density lipoprotein, 81.8%; low-density lipoprotein, 73.7%). Compliance
      rates for primary PHS behaviors were 61.6% for influenza vaccine and 57.7% for
      pneumococcal vaccine. For secondary PHS behaviors, compliance rates for
      mammography were 97.3% among women; for colonoscopy, 84%; and for bone
      densitometry (BD), 62.8%. Performance differences were observed on HL scales,
      with 31.3% and 73.7% obtaining an adequate NVS score and STOFHLA score,
      respectively, but no gender differences were noted. HL scales showed positive
      association among themselves (P = .001), patient education (NVS, P = .001;
      STOFHLA, P = .004), MMAS (P = .001 and P = .563, respectively), anthropometry
      measurements, primary PHS procedures, and 1 secondary PHS procedure
      (mammography), but they exhibited negative association with colonoscopy and BD.
      DC achieved using a PHS approach to clinical care was not associated with HL.
      CONCLUSIONS: HL was positively associated with patient education, some PHS
      behaviors, and MA. Performance on HL scales may not enable positive
      identification of PHS behaviors, DC, and MA. Thus, HL may have limited efficacy
      as a tool to assess PHS behaviors and DC among older AAs.

PMID- 30222922
TI  - Early experiences with the Acute Community Care Program in eastern Massachusetts.
AB  - OBJECTIVES: Emergency departments (EDs) frequently provide care for nonemergent
      health conditions outside of usual physician office hours. A nonprofit, fully
      integrated health insurer/care delivery system that enrolls socioeconomically
      disadvantaged adults with complex health needs partnered with an ambulance
      service provider to offer after-hours urgent care by specially trained and
      equipped paramedics in patients' residences. The Massachusetts Department of
      Public Health gave this initiative, the Acute Community Care Program (ACCP), a
      Special Project Waiver. We report results from its first 2 years of operation.
      STUDY DESIGN: This was an observational study. METHODS: We used descriptive
      methods to analyze administrative claims, financial and enrollment records from
      the health insurer, information from service logs submitted by ACCP paramedics,
      and self-reported patient perceptions from telephone surveys of ACCP recipients.
      RESULTS: ACCP averaged only about 1 call per day in its first year, growing to
      about 2 visits daily in year 2. About 15% to 20% of ACCP patients ultimately were
      transported to EDs and between 7.2% and 17.1% were hospitalized within 1 day of
      their ACCP visits. No unexpected deaths occurred within 72 hours of ACCP visits.
      Paramedics stayed on scene approximately 80 minutes on average. About 70% of
      patients thought that ACCP spared them an ED visit; 90% or more were willing to
      receive future ACCP care. Average costs per ACCP visit fell from $844 in year 1
      to $537 in year 2 as volumes increased. CONCLUSIONS: This study using
      observational data provides preliminary evidence suggesting that ACCP might offer
      an alternative to EDs for after-hours urgent care. More rigorous evaluation is
      required to assess ACCP's effectiveness.

PMID- 30222923
TI  - Economic evaluation of patient-centered care among long-term cancer survivors.
AB  - OBJECTIVES: To evaluate the economic outcomes associated with patient perceptions
      of patient-centered medical home (PCMH) characteristics among long-term cancer
      survivors in the United States. STUDY DESIGN: A retrospective analysis of the
      2008 to 2012 Medical Expenditure Panel Survey. METHODS: A nationally
      representative sample of adult long-term cancer survivors (>=3 years since
      diagnosis) was categorized into either patient-centered care (PCC) or non-PCC
      groups based on responses to PCMH model hallmark attributes of "comprehensive
      care," "whole-person orientation," and "accessible care." The positive perception
      of all 3 attributes was defined as PCC. The patient perceptions, as well as
      patient characteristics, were measured at year 1 (baseline), with a propensity
      score model to balance baseline characteristics. Adjusted total healthcare
      utilization and healthcare expenditures in 2014 US$ at year 2 (follow-up) were
      compared between the PCC and non-PCC groups. RESULTS: A total of 4288 long-term
      cancer survivors were identified, with a mean (SD) age of 65.2 (13.8) years. The
      PCC group was associated with a reduction in mean adjusted healthcare
      expenditures at follow-up (savings of $1596 per cancer survivor; P = .020). These
      findings are driven by lower odds of hospitalization (odds ratio, 0.81; 95% CI,
      0.66-0.99; P = .035) and lower hospitalization-related healthcare expenditures
      (PCC: $3323; 95% CI, $2727-$3918; non-PCC: $4912; 95% CI, $4039-$5785; P = .002)
      associated with PCC among the population who were 65 years and older. The whole
      person orientation attribute had a major impact on reduced healthcare
      expenditures. CONCLUSIONS: The positive patient perception of PCMH
      characteristics was associated with reduced healthcare expenditures in adult long
      term cancer survivors.

PMID- 30222924
TI  - Adjusting Medicare Advantage star ratings for socioeconomic status and
      disability.
AB  - OBJECTIVES: Studies have identified potential unintended effects of not adjusting
      clinical performance measures in value-based purchasing programs for
      socioeconomic status (SES) factors. We examine the impact of SES and disability
      adjustments on Medicare Advantage (MA) plans' and prescription drug plans'
      (PDPs') contract star ratings. These analyses informed the development of the
      Categorical Adjustment Index (CAI), which CMS implemented with the 2017 star
      ratings. STUDY DESIGN: Retrospective analyses of MA and PDP performance using
      2012 Medicare beneficiary-level characteristics and performance data from the
      Star Rating Program. METHODS: We modeled within-contract associations of
      beneficiary SES (Medicaid and Medicare dual eligibility [DE] or receipt of a low
      income subsidy [LIS]) and disability with performance on 16 clinical measures. We
      estimated variability in contract-level DE/LIS and disability disparities using
      mixed-effects regression models. We simulated the impact of applying the CAI to
      adjust star ratings for DE/LIS and disability to construct the 2017 star ratings.
      RESULTS: DE/LIS was negatively associated with performance for 12 of 16 measures
      and positively associated for 2 of 16 measures. Disability was negatively
      associated with performance for 11 of 15 measures and positively associated for 3
      of 15 measures. Adjusting star ratings using the CAI resulted in half-star rating
      increases for 8.5% of MA and 33.3% of PDP contracts that exceeded 50% DE/LIS
      beneficiaries. CONCLUSIONS: Increases in star ratings following adjustment of
      clinical performance for SES and disability using the CAI focused on contracts
      with higher percentages of DE/LIS beneficiaries. Adjustment for enrollee
      characteristics may improve the accuracy of quality measurement and remove
      incentives for providers to avoid caring for more challenging patient
      populations.

PMID- 30222925
TI  - Fragmented ambulatory care and subsequent healthcare utilization among Medicare
      beneficiaries.
AB  - OBJECTIVES: We sought to determine the associations between fragmented ambulatory
      care and subsequent emergency department (ED) visits and hospital admissions,
      while considering possible interactions between fragmentation and number of
      chronic conditions. STUDY DESIGN: We conducted a cohort study over 3 years among
      117,977 fee-for-service Medicare beneficiaries who were attributed to primary
      care physicians in a 7-county region of New York and had 4 or more ambulatory
      visits in the baseline year. METHODS: We calculated fragmentation scores using a
      modified Bice-Boxerman Index and, because scores were skewed, divided them into
      quintiles. We used Cox regression models to determine associations between
      fragmentation and ED visits and, separately, hospital admissions, stratifying by
      number of chronic conditions and adjusting for age, gender, number of ambulatory
      visits, and case mix. RESULTS: Among those with 1 to 2 or 3 to 4 chronic
      conditions, having the most (vs the least) fragmented care significantly
      increased the hazard of an ED visit and, separately, increased the hazard of an
      admission (adjusted P <.05 for each comparison). Among those with 5 or more
      chronic conditions, having the most fragmented care significantly increased the
      hazard of an ED visit but decreased the hazard of an admission (adjusted P <.05
      for each comparison). Among those with 0 chronic conditions, having fragmented
      care was not associated with either outcome. CONCLUSIONS: The relationship
      between fragmented ambulatory care and subsequent utilization varies with the
      number of chronic conditions. Beneficiaries with a moderate burden of chronic
      conditions (1-2 or 3-4) appear to be at highest risk of excess ED visits and
      admissions due to fragmented care.

PMID- 30222926
TI  - High-touch care leads to better outcomes and lower costs in a senior population.
AB  - OBJECTIVES: There are several models of primary care. A form of high-intensity
      care is a high-touch model that uses a high frequency of encounters to deliver
      preventive services. The aim of this study is to compare the healthcare
      utilization of patients receiving 2 models of primary care, 1 with high-touch
      care and 1 without. STUDY DESIGN: Retrospective cohort study. METHODS: We
      conducted a retrospective cohort study of 2 models of care used among Medicare
      Advantage populations. Model 1 is a high-touch care model, and model 2 is a
      standard care model. Compared with model 2, model 1 has smaller panel sizes and a
      higher frequency of encounters. We compared patients' healthcare utilization and
      hospitalizations between both models using a propensity score-matched analysis,
      matching by Charlson Comorbidity Index (CCI) score, age, and gender. RESULTS: We
      included 17,711 unmatched Medicare Advantage primary care patients and matched
      5695 patients from both models of care. CCI scores, age, and gender were similar
      between both matched groups (P >.05). The median total per member per month
      healthcare costs in model 1 were $87 (95% CI, $26-$278) compared with $121 (95%
      CI, $52-$284) in model 2 (P <.01). The mean number of hospital admissions was
      lower in model 1 (0.10 +/- 0.40) compared with model 2 (0.20 +/- 0.58). The
      number of primary care physician visits and preventive medication use were higher
      in model 1 (P <.05 for both). CONCLUSIONS: In a propensity-matched sample of
      Medicare Advantage patients, those receiving high-touch care had lower healthcare
      costs and fewer hospitalizations. Potential explanations are higher preventive
      medication use and more frequent visits.

PMID- 30222927
TI  - Zinc(II)-Catalyzed Asymmetric Diels-Alder Reaction of ( E)-1-Phenyl Dienes with
      beta,gamma-Unsaturated alpha-Ketoesters.
AB  - A highly regio-, diastereo-, and enantioselective Diels-Alder reaction of
      beta,gamma-unsaturated alpha-ketoesters with ( E)-1-phenyl dienes has been
      accomplished by using a stable and easily available chiral N,N'-dioxide/zinc(II)
      complex as catalyst. Only one isomer of the corresponding cyclohexenes with three
      chiral centers was obtained in good to excellent yields with excellent ee values
      under mild reaction conditions. The configurations of the product and chiral N,N'
      dioxide/zinc(II) catalyst were identified by X-ray diffraction analysis. In
      addition, a possible catalytic model was proposed to explain the origin of the
      asymmetric induction.

PMID- 30222928
TI  - Single-Step Reactive Electrospinning of Cell-Loaded Nanofibrous Scaffolds as
      Ready-to-Use Tissue Patches.
AB  - A reactive electrospinning strategy is used to fabricate viable and proliferative
      cell-loaded nanofibrous hydrogel scaffolds in a single step using an all-aqueous
      approach. In situ gelling and degradable hydrazone-cross-linked poly(oligo
      ethylene glycol methacrylate)-based hydrogel nanofibrous networks can be produced
      directly in the presence of cells to support long-term cell viability, adhesion,
      and proliferation, in contrast to bulk hydrogels of the same composition.
      Furthermore, the capacity of the gel nanofibers to retain bound water maintains
      this high cell viability and proliferative capacity following a freeze/thaw cycle
      without requiring any cryoprotectant additives, ideal properties for ready-to-use
      functional tissue patches.

PMID- 30222929
TI  - Impact of Polymer Bioconjugation on Protein Stability and Activity Investigated
      with Discrete Conjugates: Alternatives to PEGylation.
AB  - Covalent attachment of synthetic polymers to proteins, known as protein-polymer
      conjugation, is currently one of the main approaches for improving the
      physicochemical properties of these biomolecules. The most commonly employed
      polymer is polyethylene glycol (PEG), as evidenced by extensive research and
      clinical track records for its use in biopharmaceuticals. However, the occurrence
      of allergic reactions or hypersensitivity and the discovery of PEG antibodies, on
      the one hand, and the rise of controlled polymerization techniques and novel
      monomers, on the other hand, have been driving the search for alternative
      polymers for bioconjugation. The present study describes the synthesis,
      purification, and properties of conjugates of lysozyme with poly( N
      acryloylmorpholine) (PNAM) and poly(oligoethylene glycol methyl ether
      methacrylate) (POEGMA). Particularly, conjugate species with distinct conjugation
      degrees are investigated for their residual activity, aggregation behavior, and
      solubility, by using a high-throughput screening approach. Our study showcases
      the importance of evaluating conjugates obtained by nonsite-specific modification
      through isolated species with discrete degrees of conjugation rather than on the
      batch level. Monovalent conjugates with relatively low molar mass polymers
      displayed equal or even higher activity than the native protein, while all
      conjugates showed an improved protein solubility. To achieve a comparable effect
      on solubility as with PEG, PNAM and POEGMA of higher molar masses were required.

PMID- 30222930
TI  - EPR-Derived Structure of a Paramagnetic Intermediate Generated by Biotin Synthase
      BioB.
AB  - Biotin (vitamin B7) is an enzyme cofactor required by organisms from all branches
      of life but synthesized only in microbes and plants. In the final step of biotin
      biosynthesis, a radical S-adenosyl-l-methionine (SAM) enzyme, biotin synthase
      (BioB), converts the substrate dethiobiotin to biotin through the stepwise
      formation of two C-S bonds. Previous electron paramagnetic resonance (EPR)
      spectroscopic studies identified a semistable intermediate in the formation of
      the first C-S bond as 9-mercaptodethiobiotin linked to a paramagnetic [2Fe-2S]
      cluster through one of its bridging sulfides. Herein, we report orientation
      selected pulse EPR spectroscopic results that reveal hyperfine interactions
      between the [2Fe-2S] cluster and a number of magnetic nuclei (e.g., 57Fe, 15N,
      13C, and 2H) introduced in a site-specific manner via biosynthetic methods.
      Combining these results with quantum chemical modeling gives a structural model
      of the intermediate showing that C6, the target of the second hydrogen-atom
      abstraction, is now in close proximity to the nascent thioether sulfur and is
      ideally positioned for the second C-S bond forming event.

PMID- 30222931
TI  - Additive Polyplexes to Undertake siRNA Therapy against CDC20 and Survivin in
      Breast Cancer Cells.
AB  - Small interfering RNA (siRNA) delivered to silence overexpressed genes associated
      with malignancies is a promising targeted therapy to decrease the uncontrolled
      growth of malignant cells. To create potent delivery agents for siRNA, here we
      formulated additive polyplexes of siRNA using linoleic acid-substituted
      polyethylenimine and additive polymers (hyaluronic acid, poly(acrylic acid),
      dextran sulfate, and methyl cellulose) and characterized their physicochemical
      properties and effectiveness. Incorporating polyanionic polymer along with
      anionic siRNA in polyplexes was found to decrease the zeta-potential of
      polyplexes but enhance the cellular delivery of siRNA. The CDC20 and survivin
      siRNAs delivered by additive polyplexes showed promising efficacy in breast
      cancer MDA-MB-231, SUM149PT, MDA-MB-436, and MCF7 cells. However, the side
      effects of the siRNA delivery were observed in nonmalignant cells, and a careful
      formulation of siRNA/polymer polyplexes was needed to minimize side effects on
      normal cells. Because the efficacy of siRNA delivery by additive polyplexes was
      independent of breast cancer phenotypes used in this study, these polyplexes
      could be further developed to treat a wide range of breast cancers.

PMID- 30222932
TI  - Scaling of Rates of Vibrational Energy Transfer in Proteins with Equilibrium
      Dynamics and Entropy.
AB  - Theoretical arguments and results of molecular dynamics (MD) simulations of
      myoglobin at 300 K are presented to relate rates of vibrational energy transfer
      across nonbonded contacts interacting via short-range potentials to dynamics of
      the contact. Both theory and the results of the simulations support a scaling
      relation between the energy transfer rate and the inverse of the variance in the
      distance between hydrogen-bonded contacts. The results of the MD simulations do
      not support such a relation for longer-range charged contacts. Instead, the
      energy transfer rate is found to scale as a power law in the distance between
      charged groups. The scaling between rates of vibrational energy transfer across
      nonbonded contacts interacting via short-range potentials and conformational
      dynamics suggests a relation between vibrational energy transfer rates and
      entropy associated with the dynamics of interacting residues. The use of time
      resolved vibrational spectroscopy to determine change in conformational entropy
      with change in protein functional state is discussed, and an expression
      quantifying the connection is provided.

PMID- 30222933
TI  - PEGylated Chitosan for Nonviral Aerosol and Mucosal Delivery of the CRISPR/Cas9
      System in Vitro.
AB  - Chitosan has been widely employed to deliver nucleic acids such as siRNA and
      plasmids. However, chitosan-mediated delivery of a gene-editing system has not
      been reported yet. In this study, poly(ethylene glycol) monomethyl ether (mPEG)
      was conjugated to chitosan with different molecular weights (low molecular weight
      and medium molecular weight chitosan) achieving a high degree of substitution as
      identified by Fourier transform infrared spectroscopy (FTIR) and proton nuclear
      magnetic resonance (1H NMR) spectra. PEGylated chitosan/pSpCas9-2A-GFP
      nanocomplexes were formed at different N/ P (amine group to phosphate group)
      ratios and characterized in terms of size and zeta potential. The nanocomplexes
      developed showed the capability to protect loaded nucleic acids from DNase I
      digestion and from the stresses of nebulization. In addition, we demonstrated
      that the PEG conjugation of chitosan improved the mucus-penetration capability of
      the formed nanocomplexes at N/ P ratios of 5, 10, 20, and 30. Finally, PEGylated
      low molecular weight chitosan nanocomplexes showed optimal transfection
      efficiency at an N/ P ratio of 20, while PEGylated medium molecular weight
      chitosan nanocomplexes showed an optimal transfection efficiency at an N/ P ratio
      of 5 at pH 6.5 and 6.8. This study established the basis for the delivery of a
      gene-editing system by PEGylated chitosan nanocomplexes.

PMID- 30222934
TI  - Selective CO Evolution from Photoreduction of CO2 on a Metal-Carbide-Based
      Composite Catalyst.
AB  - A selective CO evolution from photoreduction of CO2 in water was achieved on a
      noble-metal-free, carbide-based composite catalyst, as demonstrated by a CO
      selectivity of 98.3% among all carbon-containing products and a CO evolution rate
      of 29.2 MUmol h-1, showing superiority to noble-metal-based catalyst. A rapid
      separation of the photogenerated electron-hole pairs and improved CO2 adsorption
      on the surface of the carbide component are responsible for the excellent
      performance of the catalyst. The high CO selectivity is accompanied by a
      predominant H2 evolution, which is believed to provide a proton-deficient
      environment around the catalyst to favor the formation of hydrogen-deficient
      carbon products. The present work provides general insights into the design of a
      catalyst with a high product selectivity and also the carbon evolution chemistry
      during a photocatalytic reaction.

PMID- 30222935
TI  - Ligand Sequential Replacement on Chromium(III)-Aqua Complexes by l-Alanine and
      Other Biological Amino Acids: A Kinetic Perspective.
AB  - The ligand sequential replacement on chromium(III)-aqua complexes by l-alanine in
      slightly acidic aqueous solutions (pH range: 3.55-5.61) has been kinetically
      followed by means of UV-vis spectrophotometry. A two rate constant model has been
      applied to fit the absorbance-time data, corresponding to the formation ( k1) and
      decay ( k2) of an intermediate not reactive enough to be in steady state (long
      lived intermediate). The kinetic orders of the amino acid were fractional (0.40
      +/- 0.03 for k1 and 0.40 +/- 0.02 for k2). The two steps showed base catalysis,
      and the activation energies were 60 +/- 3 (for k1) and 83 +/- 6 (for k2) kJ mol
      1. The rate constants for the coordination of the first l-alanine ligand followed
      the sequence CrOH2+ < Cr(OH)2+ < Cr(OH)3, Cr3+ being almost inactive. This
      suggests that the increase in the reaction rate with increasing pH was caused by
      the enhancement of the lability of the Cr(III)-aqua bonds induced by the presence
      of hydroxo ligands. The activation parameters for a series of ligand substitution
      on Cr(III)-aqua complexes by organic molecules yielded a statistically
      significant enthalpy-entropy linear plot with an isokinetic temperature of 296 +/
      21 K.

PMID- 30222936
TI  - Biomechanical Assessment of the NIOSH Lifting Equation in Asymmetric Load
      Handling Activities Using a Detailed Musculoskeletal Model.
AB  - OBJECTIVE: To assess adequacy of the National Institute for Occupational Safety
      and Health (NIOSH) Lifting Equation (NLE) in controlling lumbar spine loads below
      their recommended action limits during asymmetric load-handling activities using
      a detailed musculoskeletal model, that is, the AnyBody Modeling System.
      BACKGROUND: The NIOSH committee employed simplistic biomechanical models for the
      calculation of the spine compressive loads with no estimates of the shear loads.
      It is therefore unknown whether the NLE would adequately control lumbar
      compression and shear loads below their recommended action limits during
      asymmetric load-handling activities. METHOD: Twenty-four static stoop lifting
      tasks at different load asymmetry angles, heights, and horizontal distances were
      performed by one normal-weight (70 kg) and one obese (93 kg) individual. For each
      task, the recommended weight limit computed by the NLE and body segment angles
      measured by a video-camera system (VICON) were prescribed in the participant
      specific models developed in the AnyBody Modeling System that estimated spinal
      loads. RESULTS: For both individuals, the NLE adequately controlled L5-S1 loads
      below their recommended action limits for all activities performed in upright
      postures. Both individuals, however, experienced compressive and/or shear L5-S1
      loads beyond the recommended action limits when lifting was performed near the
      floor with large load asymmetry. CONCLUSION: The NLE failed to control spinal
      loads below the recommended limits during asymmetric lifting tasks performed near
      the floor. APPLICATION: The NLE should be used with caution for extreme tasks
      involving load handling near the floor with large load asymmetry.

PMID- 30222937
TI  - EFFECTS OF MYOSTATIN ON THE MECHANICAL PROPERTIES OF MUSCLES DURING REPEATED
      ACTIVE-LENGTHENING IN THE MOUSE.
AB  - : The aim of the present study was to investigate how myostatin dysfunction
      affects fast and slow muscle stiffness and viscosity during severe repeated
      loading. METHODS: Isolated extensor digitorum longus (EDL) and soleus muscles of
      young adult female mice of the BEH (dysfunctional myostatin) and BEH+/+
      (functional myostatin) strains were subjected to 100 subsequent contraction
      stretching loading cycles during which contractile and mechanical properties were
      assessed. BEH mice exhibited greater exercise-induced muscle damage, although the
      effect was muscle- and age-dependent and limited to the early phases of simulated
      exercise. The relative reduction of the EDL muscle isometric force recorded
      during the initial 10-30 loading cycles was greater in BEH mice than in BEH+/+
      mice and the soleus muscle of either strain. The induced damage was associated
      with lower muscle stiffness. The effects of myostatin on the mechanical
      properties of muscles depend on muscle type and maturity.

PMID- 30222938
TI  - Chromosome painting of the red-handed tamarin (Saguinus midas) compared to other
      Callitrichinae monkeys.
AB  - Here we present, for the first time, the complete chromosome painting map of
      Saguinus midas, the red-handed tamarin. Chromosome banding and painting with
      human chromosome-specific probes were used to compare the karyotype of this
      species with those of four other Neotropical primates of the subfamily
      Callitrichinae: Leontopithecus rosalia, Callithrix geoffroyi, C. penicillata, and
      Mico argentatus. The chromosome painting map of S. midas was identical to that of
      L. rosalia and other previously studied tamarin species (genera Saguinus and
      Leontopithecus). The three marmoset species studied (genera Callithrix and Mico)
      differed in the painting pattern of four human probes (chromosomes 1, 2, 10, and
      16). These paints identified the presence or absence of chromosome associations
      HSA 1/10 and 2/16 in these taxa. By integrating our data with those from the
      literature, we were able to propose an ancestral Callitrichinae karyotype. The
      genera Saguinus and Leontopithecus (tamarins) conserve the ancestral
      Callitrichinae karyotype, while Mico and Callithrix (marmosets) show more derived
      karyotypes due to chromosome translocations and fissions that occurred during the
      evolution of these taxa.

PMID- 30222939
TI  - The impact of surgeon volume on perioperative adverse events in women undergoing
      minimally invasive hysterectomy for the large uterus.
AB  - BACKGROUND: There are currently sparse data on the relationship between surgeon-
      and patient-related factors and perioperative morbidity in the setting of
      elective hysterectomy for the larger uterus. OBJECTIVE: We sought to evaluate the
      impact of surgeon case volume on perioperative adverse events in women undergoing
      minimally invasive hysterectomy for uteri >250 g. STUDY DESIGN: This is a
      retrospective cohort study of all women who underwent total vaginal, total
      laparoscopic, laparoscopic-assisted vaginal, or robotic-assisted total
      laparoscopic hysterectomy from January 2014 through July 2016. Hysterectomy was
      performed for: fibroids, pelvic pain, abnormal uterine bleeding, or prolapse.
      Patients were identified by Current Procedural Terminology codes and the
      systemwide electronic medical record was queried for demographic and
      perioperative data. Perioperative adverse events were defined a priori and
      classified using the Clavien-Dindo scale. Surgeon case volume was defined as the
      mean number of minimally invasive hysterectomy cases performed per month by each
      surgeon during the study period. RESULTS: In all, 763 patients met inclusion
      criteria: 416 (54.5%) total laparoscopic hysterectomy, 196 (25.7%) robotic
      assisted total laparoscopic hysterectomy, 90 (11.8%) total vaginal hysterectomy,
      and 61 (8%) laparoscopic-assisted vaginal hysterectomy. Mean (+/-SD) age was 47.3
      +/- 6.1 years, and body mass index was 31.1 +/- 7.4 kg/m2. In all, 66 surgeons
      performed minimally invasive hysterectomy for uteri >250 g during the study
      period, and the median rate of minimally invasive hysterectomy cases for large
      uteri per month was 3.4 (0.4-3.7) cases/month. The median (IQR) uterine weight
      was 409 (308-606.5) g. The rate of postoperative adverse events Dindo grade >2
      was 17.8% (95% confidence interval, 15.2-20.7). The overall rate of
      intraoperative adverse events was 4.2% (95% confidence interval, 2.9-5.9). The
      rate of conversion to laparotomy was 5.5% (95% confidence interval, 4.0-7.4).
      There was no significant difference in adverse event rates between the routes of
      minimally invasive hysterectomy cases (25.6% vs 17.5% vs 18.0% vs 14.8% for total
      laparoscopic hysterectomy, robotic-assisted laparoscopic hysterectomy, total
      vaginal hysterectomy, and laparoscopic-assisted vaginal hysterectomy,
      respectively, P = .2). In a logistic regression model controlling for age, body
      mass index, uterine weight, operating time, and history of laparotomy, higher
      monthly minimally invasive hysterectomy volume was significantly associated with
      the likelihood that a patient would experience a postoperative adverse event
      (adjusted odds ratio, 1.1 for each additional minimally invasive hysterectomy
      case for large uteri per month; 95% confidence interval, 1.0-1.3). When
      controlling for the same variables, a higher incidence of intraoperative
      complications was significantly associated with monthly minimally invasive
      hysterectomy case volume (adjusted odds ratio, 1.5 for each additional minimally
      invasive hysterectomy case for large uteri per month; 95% confidence interval,
      1.20-2.08). Increasing age was associated with a lower incidence of complications
      (adjusted odds ratio, 0.9 for each additional year; 95% confidence interval, 0.8
      0.9). Higher monthly minimally invasive hysterectomy volume was associated with a
      lower rate of conversion from a minimally invasive approach to laparotomy
      (adjusted odds ratio, 0.4 for each additional minimally invasive hysterectomy
      case for large uteri per month; 95% confidence interval, 0.2-0.5). CONCLUSION:
      The overall rate of serious adverse events associated with minimally invasive
      hysterectomy for uteri >250 g was low. Higher monthly minimally invasive
      hysterectomy case volume was associated with a higher rate of intraoperative and
      postoperative adverse events but was associated with a lower rate of conversion
      to laparotomy.

PMID- 30222940
TI  - Does Autophagy Promote or Protect Against the Pathogenesis of Pancreatitis?

PMID- 30222941
TI  - Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs:
      What About Perforations and the Healing Intestine?

PMID- 30222942
TI  - Therapeutic Targets in Inflammatory Bowel Disease: Are We Getting the Point
      Across?

PMID- 30222943
TI  - Ponder the Innate Immunity in Hepatitis B Infection.

PMID- 30222944
TI  - Minimally Invasive Ivor Lewis Esophagectomy: How I Teach It.

PMID- 30222946
TI  - High prevalence of parkinsonism in patients with MCI or mild Alzheimer's disease.
AB  - INTRODUCTION: The objective of this study was to examine the prevalence of the
      coexistence of parkinsonism in patients with mild cognitive impairment (MCI) or
      mild Alzheimer's disease (AD). METHODS: Outpatients were evaluated with Mini
      Mental State Examination, Clinical Dementia Rating Scale, NIA-AA criteria, MRI,
      and 123I-IMP SPECT (3D-SSP). Parkinsonism in patients diagnosed with MCI (Mini
      Mental State Examination >=24, n = 63) or mild AD (Mini-Mental State Examination
      20-23, n = 43) was examined using the Unified Parkinson's Disease Rating Scale
      III and 123I-FP-CIT dopamine transporter SPECT. RESULTS: One hundred six patients
      (60-97 years) were enrolled. Fifty-six patients (52.8%) were diagnosed as having
      concomitant parkinsonism with rigidity and resting tremor and dopamine
      transporter reduction in the basal ganglia. The mean (SD) age (n = 56) was 80.6
      (6.1) years, significantly older than patients without parkinsonism [77.6 (7.0)
      years, n = 50] (P < .05). The mean (SD) UPDRS-III score was 5.8 (2.4).
      CONCLUSION: The prevalence rate of the coexistence of mild parkinsonism in MCI or
      mild AD may be higher than previously recognized.

PMID- 30222948
TI  - Editorial Comment.

PMID- 30222947
TI  - Editorial Comment.

PMID- 30222945
TI  - Whitepaper: Defining and investigating cognitive reserve, brain reserve, and
      brain maintenance.
AB  - Several concepts, which in the aggregate get might be used to account for
      "resilience" against age- and disease-related changes, have been the subject of
      much research. These include brain reserve, cognitive reserve, and brain
      maintenance. However, different investigators have use these terms in different
      ways, and there has never been an attempt to arrive at consensus on the
      definition of these concepts. Furthermore, there has been confusion regarding the
      measurement of these constructs and the appropriate ways to apply them to
      research. Therefore the reserve, resilience, and protective factors professional
      interest area, established under the auspices of the Alzheimer's Association,
      established a whitepaper workgroup to develop consensus definitions for cognitive
      reserve, brain reserve, and brain maintenance. The workgroup also evaluated
      measures that have been used to implement these concepts in research settings and
      developed guidelines for research that explores or utilizes these concepts. The
      workgroup hopes that this whitepaper will form a reference point for researchers
      in this area and facilitate research by supplying a common language.

PMID- 30222949
TI  - microRNA-141-3p fosters the growth, invasion, and tumorigenesis of cervical
      cancer cells by targeting FOXA2.
AB  - microRNA (miR)-141-3p has context-dependent effects on tumor progression. In this
      study, we attempted to explore the expression and function of miR-141-3p in
      cervical cancer. We found that miR-141-3p expression was significantly increased
      in cervical cancer specimens relative to normal cervical tissues. Moreover, miR
      141-3p levels were associated with tumor size and lymph node metastasis status.
      Ectopic expression of miR-141-3p significantly increased cervical cancer cell
      proliferation, colony formation, invasion, and epithelial to mesenchymal
      transition, whereas depletion of miR-141-3p suppressed cervical cancer cell
      proliferation and invasion. FOXA2 was identified to be a target of miR-141-3p.
      Overexpression of miR-141-3p led to a marked inhibition of endogenous FOXA2 in
      cervical cancer cells. FOXA2 silencing phenocopied the effects of miR-141-3p
      overexpression on cervical cancer cell proliferation and invasion. Enforced
      expression of FOXA2 blocked the effects of miR-141-3p on cervical cancer cell
      proliferation and invasion. miR-141-3p overexpression significantly accelerated
      the growth of xenograft tumors, which was accompanied by a striking reduction in
      FOXA2 expression. miR-141-3p acts as an oncogene in cervical cancer largely
      through repression of FOXA2. Targeting miR-141-3p may represent a potential
      therapeutic strategy for cervical cancer.

PMID- 30222950
TI  - In vitro characterization of N-terminal truncated EpsC from Bacillus subtilis
      168, a UDP-N-acetylglucosamine 4,6-dehydratase.
AB  - Bacillus subtilis 168 EpsC is annotated as "Probable polysaccharide biosynthesis
      protein" in the SwissProt database. epsC is part of the eps operon, thought to be
      involved in the biosynthesis of exopolymeric substances (EPS). The present study
      was undertaken to determine the molecular function of EpsC. Sequence analysis of
      EpsC suggested the presence of a transmembrane domain. Two N-terminal deletion
      mutants in which residues 1-89 (EpsC89) and 1-115 (EpsC115) are deleted were
      cloned and overexpressed. Enzyme activity and substrate preferences were
      investigated by reverse phase HPLC, surface plasmon resonance (SPR) spectroscopy
      and absorption spectroscopy. These data show that EpsC has UDP-GlcNAc 4,6
      dehydratase activity in vitro. Purified recombinant proteins were found to
      utilise UDP-Glc and TDP-Glc also as substrates. In addition, EpsC115 could
      utilise UDP-Gal and UDP-GalNAc as substrates whereas EpsC89 could only bind these
      two sugar nucleotides. These results show that deletion of a longer N-terminal
      region broadens substrate specificity. These broadened specificity is perhaps an
      outcome of the deletion of the putative transmembrane domain and may not be
      present in vivo. EpsC, together with the aminotransferase EpsN (Kaundinya CR et
      al., Glycobiology, 2018) and acetyltransferase EpsM (unpublished data), appears
      to be involved in the biosynthesis of N,N'-diacetylbacillosamine.

PMID- 30222951
TI  - Extracellular loop 3 substitutions K589N and A590S in FSH receptor increase FSH
      induced receptor internalization and along with S588T substitution exhibit
      impaired ERK1/2 phosphorylation.
AB  - The interaction of follicle stimulating hormone with its specific GPCR, the
      follicle stimulating hormone receptor (FSHR) is facilitated by the extracellular
      loops (ELs) which contact the transmembrane domain and relay the signal
      downstream. In order to determine the contribution of non conserved residues from
      the EL3 of FSHR in conferring specificity to FSH-FSHR interaction, they were
      swapped with respective residues from luteinizing hormone/choriogonadotropin
      receptor. The triple mutant EL3M exhibited increased internalization of FSH-FSHR
      complexes without affecting the cAMP signaling response. Here, substitution point
      mutants S588T, K589N and A590S of the EL3 of FSHR were generated and
      characterized. None of these substitutions affected FSHR expression, FSH binding
      ability and cAMP production as compared to wild type FSHR. However, the high
      internalization of EL3M was observed to be due to the K589N and A590S
      substitutions. Further, all the mutants showed an impaired FSH mediated ERK
      phosphorylation response and the extent of impairment was most striking in case
      of the A590S substitution. Interestingly, S588T mutant exhibited impaired ERK
      phosphorylation, without change in receptor internalization, indicating that
      these processes can be dissociated. Thus, the FSHR specific residues K589 and
      A590 in the EL3 of FSHR seem to be crucial for FSH-induced internalization and
      ERK phosphorylation.

PMID- 30222952
TI  - Fruticulosin: A novel type 2 ribosome-inactivating protein from Abrus
      fruticulosus seeds that exhibits toxic and antileishmanial activity.
AB  - Plant ribosome-inactivating proteins (RIPs) are a family of toxins that inhibit
      protein synthesis. In this study, we have isolated a novel type 2 ribosome
      inactivating protein (RIP) present in seeds of the Abrus fruticulosus, named of
      fruticulosin. Fruticulosin, shows characteristics common to other type 2 RIPs, as
      specificity by galactosides (d-galactose, N-acetyl-d-galactosamine, and d
      lactose), mass of approximately 60 kDa and presence of the of disulfide bonds.
      The N-terminal amino acid sequence (26 residues) of A-chain fruticulosin,
      determined by Edman degradation, revealed high similarity of the A-chain with
      those of other type 2 RIPs. The secondary structure of fruticulosin was analysed
      by circular dichroism, which showed that fruticulosin contains alpha-helices
      (22.3%), beta-sheets (43.5%), and random coils and corners (34.2%). Furthermore,
      fruticulosin showed high toxicity in Artemia sp. (3.12 MUg/mL), inhibited in
      vitro protein synthesis by a cell-free system and showed RNA N-glycosidase
      activity. Fruticulosin presented biological activities such as agglutination and
      antileishmanial activity on promastigote forms of Leishmania major.

PMID- 30222953
TI  - Astragaloside exerts anti-photoaging effects in UVB-induced premature senescence
      of rat dermal fibroblasts through enhanced autophagy.
AB  - BACKGROUND: Astragalus membranaceus is a fundamental herb in Traditional Chinese
      Medicine and has attracted significant attention due to its anti-inflammatory,
      and longevity effects. However, its anti-photoaging property remains to be
      defined. Autophagy plays important roles in regulating cell homeostasis and aging
      processes. Whether regulation of autophagy could be an efficient way for anti
      photoaging is still unclear. OBJECTIVE: To investigate the effects and the
      possible mechanism of astragaloside on anti-photoaging in UVB-induced photoaging
      cell model. METHODS: Primary rat dermal fibroblasts were prepared by repeated
      exposures to UVB irradiation. The expression levels of cytokines and signal
      molecules were determined by RT-PCR and western blot. SA-beta-gal staining was
      performed to indicate senescence level. Intracellular reactive oxygen species and
      mitochondrial membrane potential were monitored by fluorescent probes DCFH-DA and
      JC-1. The cell viability was determined using Cell Counting Kit-8. RESULTS:
      Astragaloside increases the expression of collagen-I (Col1) downregulated by UVB.
      UVB-induced oxidative stress and photoaging could be inhibited by astragaloside.
      The degradation of Col1 caused by UVB irradiation through activated ERK and p38
      signals could be suppressed by astragaloside. Importantly, autophagy was induced
      by astragaloside. Col1 could be further accumulated by chloroquine but decreased
      by 3-methyladenine in photoaged cell after treatment of astragaloside.
      CONCLUSION: Autophagy play essential roles, at least partially, in modulating the
      formation and degradation of Col1 in photoaging cell model. Astragaloside
      increases the accumulation of Col1 and protects UVB-induced photoaging cells
      through not only ERK and p38 inhibition but also autophagy activation, indicating
      the potential application of astragaloside for anti-photoaging therapy.

PMID- 30222955
TI  - Re: D-pinitol attenuates cisplatin-induced nephrotoxicity in rats: Impact on
      proinflammatory cytokines.

PMID- 30222954
TI  - Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5.
AB  - Tobacco and alcohol are often co-abused. Nicotine can enhance alcoholic fatty
      liver, and CYP2A6 (CYP2A5 in mice), a major metabolism enzyme for nicotine, can
      be induced by alcohol. CYP2A5 knockout (cyp2a5-/-) mice and their littermates
      (cyp2a5+/+) were used to test whether CYP2A5 has an effect on nicotine-enhanced
      alcoholic fatty liver. The results showed that alcoholic fatty liver was enhanced
      by nicotine in cyp2a5+/+ mice but not in the cyp2a5-/- mice. Combination of
      ethanol and nicotine increased serum triglyceride in cyp2a5+/+ mice but not in
      the cyp2a5-/- mice. Cotinine, a major metabolite of nicotine, also enhanced
      alcoholic fatty liver, which was also observed in cyp2a5+/+ mice but not in the
      cyp2a5-/- mice. Nitrotyrosine and malondialdehyde (MDA), markers of
      oxidative/nitrosative stress, were induced by alcohol and were further increased
      by nicotine and cotinine in cyp2a5+/+ mice but not in the cyp2a5-/- mice.
      Reactive oxygen species (ROS) production during microsomal metabolism of nicotine
      and cotinine was increased in microsomes from cyp2a5+/+ mice but not in
      microsomes from cyp2a5-/- mice. These results suggest that nicotine enhances
      alcoholic fatty liver in a CYP2A5-dependent manner, which is related to ROS
      produced during the process of CYP2A5-dependent nicotine metabolism.

PMID- 30222956
TI  - Bioactivity under laboratory conditions of Brevibacillus laterosporus towards
      larvae and adults of Chrysomya putoria (Diptera: Calliphoridae).
AB  - Brevibacillus laterosporus was tested for entomopathogenic activity towards
      larvae and adults of Chrysomya putoria (Diptera: Calliphoridae) under laboratory
      conditions. Sublethal effects related to feeding activity or development were
      observed, including reduction in larval weight gain, probably by inhibition of
      feeding, and variation in the duration of the developmental stages of the insect.
      Larval mortality was dose dependent following ingestion. The experiments were
      performed with newly emerged adults exposed to a sugar based diet containing
      spore suspensions. Concentrations of 1.13 * 109 CFU/ml caused 70.5% of mortality.
      The present study highlights the potential of B. laterosporus to control
      populations of C. putoria, a dipteran of medical-veterinary and sanitary
      importance, both in larval and adult stages.

PMID- 30222958
TI  - Identification of insulin-regulated aminopeptidase (IRAP) in the rat pineal gland
      and the modulation of melatonin synthesis by angiotensin IV.
AB  - A local renin-angiotensin system (RAS) has been postulated in the pineal gland.
      In addition to angiotensin II (Ang II), other active metabolites have been
      described. In this study, we aimed to investigate a role for Ang IV in melatonin
      synthesis and the presence of its proposed (IRAP)/AT4 receptor (insulin-regulated
      aminopeptidase) in the pineal gland. The effect of Ang IV on melatonin synthesis
      was investigated in vitro using isolated pinealocytes. IRAP protein expression
      and activity were evaluated by Western blot and fluorimetry using Leu-4Me-beta
      naphthylamide as a substrate. Melatonin was analyzed by HPLC, calcium content by
      confocal microscopy and cAMP by immunoassay. Ang IV significantly augmented the
      NE-induced melatonin synthesis to a similar degree as that achieved by Ang II.
      This Ang IV effect in pinealocytes appears to be mediated by an increase in the
      intracellular calcium content but not by cAMP. The (IRAP)/AT4 expression and
      activity were identified in the pineal gland, which were significantly higher in
      membrane fractions than in soluble fractions. Ang IV significantly reduced IRAP
      activity in the pineal membrane fractions. The main findings of the present study
      are as follows: (1) Ang IV potentiates NE-stimulated melatonin production in
      pinealocytes, (2) the (IRAP)/AT4 receptor is present in the rat pineal gland, and
      (3) Ang IV inhibits IRAP activity and increases pinealocytes [Ca2+]i. We conclude
      that Ang IV is an important component of RAS and modulates melatonin synthesis in
      the rat pineal gland.

PMID- 30222959
TI  - Neurostimulation Treatment of OSA.
AB  - Over the past 30 years, hypoglossal nerve stimulation has moved through a
      development pathway to become a viable treatment modality for patients with OSA.
      Initial pilot studies in animals and humans laid the conceptual foundation for
      this approach, leading to the development of fully implantable stimulating
      systems for therapeutic purposes. These devices were then shown to be both safe
      and efficacious in feasibility studies. One such closed-loop stimulating device
      was found to be effective in treating a limited spectrum of apneic patients and
      is currently approved by the US Food and Drug Administration for this purpose.
      Another open-loop stimulating system is currently being rigorously tested in a
      pivotal trial. Collectively, clinical trials of hypoglossal nerve stimulating
      systems have yielded important insights that can help optimize therapeutic
      responses to hypoglossal nerve stimulation. These insights include specific
      patient selection criteria and methods for delivering stimulation to specific
      portions of the hypoglossal nerve and/or genioglossus muscle. New approaches for
      activating efferent and afferent motor pathways are currently in early-stage
      laboratory development and hold some long-term promise as a novel therapy.

PMID- 30222957
TI  - Stage-specific roles of Ezh2 and Retinoic acid signaling ensure calvarial bone
      lineage commitment.
AB  - Development of the skull bones requires the coordination of two stem progenitor
      populations, the cranial neural crest cells (CNCC) and head paraxial mesoderm
      (PM), to ensure cell fate selection and morphogenesis. The epigenetic
      methyltransferase, Ezh2, plays a role in skull bone formation, but the
      spatiotemporal function of Ezh2 between the CNCC- and PM-derived bone formation
      in vivo remains undefined. Here, using a temporally-inducible conditional
      deletion of Ezh2 in both the CNCC- and PM- derived cranial mesenchyme between
      E8.5 and E9.5, we find a reduction of the CNCC-derived calvarial bones and a near
      complete loss of the PM-derived calvarial bones due to an arrest in calvarial
      bone fate commitment. In contrast, deletion of Ezh2 after E9.5 permits PM-derived
      skull bone development, suggesting that Ezh2 is required early to guide calvarial
      bone progenitor commitment. Furthermore, exposure to all-trans Retinoic acid at
      E10.0 can mimic the Ezh2 mutant calvarial phenotype, and administration of the
      pan retinoic acid receptor (RAR) antagonist, BMS-453, to Ezh2 mutants partially
      restores the commitment to the calvarial bone lineage and PM-derived bone
      development in vivo. Exogenous RA signaling activation in the Ezh2 mutants leads
      to synergistic activation of the anti-osteogenic factors in the cranial
      mesenchyme in vivo. Thus, RA signaling and EZH2 can function in parallel to guide
      calvarial bone progenitor commitment by balancing the suppression of anti
      osteogenic factors.

PMID- 30222960
TI  - A novel combined score of biomarkers in sputum may be an indicator for lung
      cancer: A pilot study.
AB  - BACKGROUND: Lung cancer is a leading cause of morbidity and mortality worldwide
      and there is an urgent need for sensitive, specific, and reliable biomarkers.
      METHODS: The study population included 60 patients (31 with lung cancer and 29
      with chronic obstructive pulmonary disease [COPD]) and thirty healthy individuals
      comprised the control group. Measurements of neutrophil, beclin-1, VEGF, ICAM,
      VCAM, and TNF-alpha levels in induced sputum were analyzed as possible biomarkers
      for lung cancer. RESULTS: Neutrophil, beclin-1, VEGF, ICAM and TNF-alpha levels
      of lung cancer patients differed significantly compared to those of COPD patients
      and healthy controls. A novel combined-score was created which was found to
      increase the likelihood to belong to the cancer group by 70% (odds-ratio 1.70 CI
      = 1.310-2.224,p < 0.001). CONCLUSION: Biomarkers of autophagy, angiogenesis and
      inflammation in lung-cancer patients are significantly different from controls,
      and combination of these markers may be an indicator for lung cancer.

PMID- 30222961
TI  - Effect of delayed cell processing and cryopreservation on immunophenotyping in
      multicenter population studies.
AB  - Variability induced by delayed cell processing and cell cryopreservation presents
      unique challenges for immunophenotyping in large population studies. We conducted
      a pilot study to evaluate the effect of delayed cell processing and
      cryopreservation on cell percentages obtained by immunophenotyping. We collected
      blood from 20 volunteers and compared the effect of (a) delayed cell processing
      up to 72 h (b) cryopreservation and (c) the combined effect of delayed cell
      processing and cryopreservation on immunophenotyping of 31 cell subsets that
      included several subsets of T, B, Natural Killer (NK) cells, monocytes and
      dendritic cells using both whole blood collected in EDTA tubes and peripheral
      blood mononuclear cells collected in CPT tubes. We found the delayed cell
      processing up to 72 h or cryopreservation alone did not significantly affect the
      percentages T cells, dendritic cells or monocytes but significantly increased the
      percentage of B cells and NK cells (p for trend <=0.01) but. However combination
      of delayed cell processing up to 72 h and cryopreservation significantly
      increased the percentage of T cells as compared to cells processed immediately (p
      for trend <0.0001) while a delayed cell processing followed by cryopreservation
      decreased the percentage of NK cells (p for trend <0.0001). Total B-cells
      increased significantly with a 24-48 h delay in cell processing and
      cryopreservation but not at 72 h. The percentages of monocytes and dendritic
      cells remained unaffected by the combination of delayed cell processing and
      cryopreservation. These findings suggest that immunophenotyping of several immune
      cell subsets can be successfully implemented in large population studies as long
      as blood is processed within 48 h of biospecimen collection though some cell
      subsets may be more susceptible to a combination of delayed cell processing and
      cryopreservation.

PMID- 30222963
TI  - Basic reproduction number for the Brazilian Spotted Fever.
AB  - Brazilian Spotted Fever (BSF) is an emerging and lethal disease in South America
      which basic reproduction number (R0) is unknown. Calculating R0 for this disease
      is crucial to design control interventions and prevent human deaths. BSF endemic
      areas are related to the presence of capybaras Hydrochoerus hydrochaeris,
      amplifier hosts of Rickettsia rickettsii and primary hosts of the tick Amblyomma
      sculptum, main vector of the agent in this area. Because of the complexity of its
      dynamics, we calculated R0 for the BSF system by constructing a next-generation
      matrix considering different categories of vectors and hosts. Each matrix element
      was considered as the expected number of infected individuals of one category
      produced by a single infected individual of a second category. We used field and
      experimental data to parameterize the next-generation matrix and obtain the final
      calculation (R0 ~ 1.7). We demonstrated the low impact of the matrix elements
      corresponding to the transovarial transmission and the transmission from infected
      larvae in the maintenance of R. rickettsii. Sensitivity and elasticity analyzes
      were performed to quantify the perturbations of each matrix element in R0. We
      noted that the elements equivalent to the number of infected attached nymphs
      produced by an infected capybara, and the number of infected capybaras produced
      by an infected attached nymph or adult are the major contributors to changes in
      R0. Our results provide insights into the strategic design of preventive
      interventions in BSF endemic areas.

PMID- 30222962
TI  - Factors Associated With Histologic Response in Adult Patients With Nonalcoholic
      Steatohepatitis.
AB  - BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a leading cause of
      liver transplantation, and many trials are underway to evaluate potential
      therapies. The farnesoid X receptor ligand obeticholic acid in the NASH treatment
      trial evaluated the effects of obeticholic acid vs placebo on histologic response
      (defined as decrease in nonalcoholic fatty liver disease activity score [NAS] by
      >=2, with no worsening of fibrosis); 45% of patients had a histologic response to
      obeticholic acid (25 mg), and 21% had a response to placebo (P < .01). We
      performed a secondary analysis of data from this trial to identify clinical
      parameters associated with a histologic response. METHODS: We used a logistic
      regression model with a stepwise selection procedure to identify baseline and
      early on-treatment factors associated with a histologic response at 72 weeks.
      Baseline demographics, liver histology, medical history, concomitant medications,
      cardiometabolic parameters, and serum biochemistry, as well as the changes over
      the course of the trial (at weeks 12 and 24), were evaluated as potential
      predictors of a histologic response. The model was cross-validated by a jackknife
      method, and performance was evaluated with the area under the receiver operating
      characteristic curve. RESULTS: The logistic regression model found that
      obeticholic acid treatment, baseline NAS > 5, baseline triglyceride level <= 154
      mg/dL, baseline international normalized ratio <= 1, baseline aspartate
      aminotransferase level <= 49 U/L, and a decrease in alanine aminotransferase
      level at week 24 by 17 U/L or more, to be significantly associated with
      histologic response (area under the receiver operating characteristic curve,
      0.83; 95% confidence interval, 0.77-0.89; P < .0001). CONCLUSIONS: In a secondary
      analysis of data from a clinical trial of obeticholic acid in patients with NASH,
      we identified routine clinical and laboratory parameters during the first 24
      weeks of treatment (such as baseline NAS, triglyceride levels, and a decrease in
      alanine aminotransferase level) to significantly associate with histologic
      markers of response.

PMID- 30222964
TI  - Modeling the crosstalk between the circadian clock and ROS in Neurospora crassa.
AB  - The circadian clock regulates the expression of clock-controlled genes and adapts
      to environmental changes. Reactive oxygen species (ROS) also undergo circadian
      rhythms and have a role in circadian timekeeping. To elucidate crosstalk between
      ROS and the circadian clock in Neurospora crassa, we build an integrative network
      model, characterizing the circadian oscillator, ROS system and their
      interactions. Notably, the (de)phosphorylation and nuclear-cytoplasmic shuttling
      of clock proteins are modeled in detail. Simulation results quantitatively
      reproduce the essential features of circadian rhythm (both in constant darkness
      and under light/dark cycles) and the changes in period length and phase when ROS
      levels are altered under diverse conditions. This work clarifies the effects of
      three interactions between ROS and the clock on the circadian rhythm, suggesting
      that the regulation of WCC activity by protein phosphatase 2A in an O2--dependent
      manner plays a predominant role. The functional significance of such modulations
      is also discussed.

PMID- 30222965
TI  - Computational systems biology approach to identify novel pharmacological targets
      for diabetic retinopathy.
AB  - Diabetic retinopathy was included by the World Health Organization in the eye
      disease priority list. Up to now, only proliferative diabetic retinopathy can be
      treated with approved drugs, such as intravitreal anti-vascular endothelial
      growth factor (VEGF) agents or steroids. In this perspective, there is the urgent
      need to explore novel pharmacological targets for treatment of diabetic
      retinopathy. Drug discovery todays exploits the noticeable ability of
      computational systems biology methods to identify novel drug targets in complex
      pathologies bearing multifactorial etiology and wide and varying symptomatology.
      This is especially true for diseases, where the identification of specific
      molecular mechanisms, and thus drug targets, is a challenging, when not
      impossible, task. Within this framework, we applied a systems biology approach to
      identify novel drug targets for diabetic retinopathy. The complexity of diabetic
      retinopathy was investigated through the analysis of transcriptomics data,
      retrieved from Gene Expression Omnibus Dataset repository (GEO) datasets.
      Analysis of GEO datasets was carried out with an enrichment-information approach,
      which gave as output a series of complex gene-pathway and drug-gene networks.
      Analysis of these networks identified genes and biological pathways related with
      inflammation, fibrosis and G protein-coupled receptors that are potentially
      involved in development of the disease. This analysis provided new clues on novel
      pharmacological targets, useful to treat diabetic retinopathy.

PMID- 30222966
TI  - Specific tissue factor delivery using a tumor-homing peptide for inducing tumor
      infarction.
AB  - Targeting the human blood coagulation-inducing protein tissue factor (TF) to the
      tumor vasculature to induce infarction and disrupt the blood vessels has proven
      to be an effective approach for tumor therapy. In this study, we investigated the
      thrombogenic activity and anti-tumor potential of a novel fusion protein (tTF
      CREKA) comprising the extracellular domain of human tissue factor (truncated TF,
      tTF) and a tumor targeting pentapeptide, Cys-Arg-Glu-Lys-Ala (CREKA). tTF is
      soluble and inactive in its free state, but when it is targeted to the plasma
      membrane of both tumor vessel endothelial cells and stromal cells by the CREKA
      peptide, its native coagulation-inducing activity is restored. Systemic
      administration of the tTF-CREKA fusion protein into tumor-bearing mice induced
      tumor-selective intravascular thrombosis and reduced tumor blood perfusion,
      consequently inhibiting tumor growth. The development of tTF-CREKA introduces a
      new method for treating a wide spectrum of solid tumors by selectively blocking
      tumor blood supply.

PMID- 30222967
TI  - LKB1 loss is associated with glutathione deficiency under oxidative stress and
      sensitivity of cancer cells to cytotoxic drugs and gamma-irradiation.
AB  - The liver kinase B1 (LKB1) gene is a tumor suppressor associated with the
      hereditary Peutz-Jeghers syndrome and frequently mutated in non-small cell lung
      cancer and in cervical cancer. Previous studies showed that the LKB1/AMPK axis is
      involved in regulation of cell death and survival under metabolic stress. By
      using isogenic pairs of cancer cell lines, we report here that the genetic loss
      of LKB1 was associated with increased intracellular levels of total choline
      containing metabolites and, under oxidative stress, it impaired maintenance of
      glutathione (GSH) levels. This resulted in markedly increased intracellular
      reactive oxygen species (ROS) levels and sensitivity to ROS-induced cell death.
      These effects were rescued by re-expression of LKB1 or pre-treatment with the
      anti-oxidant and GSH replenisher N-acetyl cysteine. This role of LKB1 in response
      to ROS-inducing agents was largely AMPK-dependent. Finally, we observed that LKB1
      defective cells are highly sensitive to cisplatin and gamma-irradiation in vitro,
      suggesting that LKB1 mutated tumors could be targeted by oxidative stress
      inducing therapies.

PMID- 30222968
TI  - About canonical, non-canonical and immunogenic cell death: Basic mechanisms and
      translational applications: A meeting report of the International Cell Death
      Society.
AB  - International Cell Death Society held its 25th meeting, entitled "About
      canonical, non-canonical, and immunogenic cell death: basic mechanisms and
      translational applications" in Seoul, South Korea, May 31-June 2, 2018, addressed
      the most current issues in the field. Now that many types and pathways of cell
      death are recognized, attention has turned to how the threshold to death is
      maintained or surpassed, and how and what intracellular signals control the
      process. Most of the speakers addressed these topics, focusing on mitochondria
      and on new high-resolution techniques that promise to answer current questions.

PMID- 30222969
TI  - Pancreatic ductal adenocarcinoma cell secreted extracellular vesicles containing
      ceramide-1-phosphate promote pancreatic cancer stem cell motility.
AB  - The high mortality rate associated with pancreatic ductal adenocarcinoma (PDAC)
      is in part due to lack of effective therapy for this highly chemoresistant tumor.
      Cancer stem cells, a subset of cancer cells responsible for tumor initiation and
      metastasis, are not targeted by conventional cytotoxic agents, which renders the
      identification of factors that facilitate cancer stem cell activation useful in
      defining targetable mechanisms. We determined that bioactive sphingolipid induced
      migration of pancreatic cancer stem cells (PCSC) and signaling was specific to
      ceramide-1-phosphate (C1P). Furthermore, PDAC cells were identified as a rich
      source of C1P. Importantly, PDAC cells express the C1P converting enzyme ceramide
      kinase (CerK), secrete C1P-containing extracellular vesicles that mediate PCSC
      migration, and when co-injected with PCSC reduce animal survival in a PDAC
      peritoneal dissemination model. Our findings suggest that PDAC secrete C1P
      containing extracellular vesicles as a means of recruiting PCSC to sustain tumor
      growth therefore making C1P release a mechanism that could facilitate tumor
      progression.

PMID- 30222970
TI  - Metformin downregulates the mitochondrial carrier SLC25A10 in a glucose dependent
      manner.
AB  - Metformin, a commonly used agent in the treatment of type 2 diabetes, is also
      associated with reduced risk of cancer development and improvement in cancer
      survival. Although much is known about metformin, the mechanisms behind its anti
      cancer properties are not fully understood. In this study we addressed the role
      of a mitochondrial transporter commonly upregulated in cancer cells, SLC25A10,
      for cell survival and metabolism in the presence of metformin. SLC25A10 is a
      carrier in the mitochondrial inner membrane that transports malate and succinate
      out of the mitochondria, in exchange of phosphate and sulfate. We show that
      metformin treatment results in decreased gene expression of the SLC25A10 carrier
      both in lung cancer A549 mock cells and A549 SLC25A10 knockdown (siSLC25A10)
      cells. The decrease was even more pronounced when cells were grown at low glucose
      concentrations. The expression levels of key enzymes in glucose metabolism showed
      slightly altered mean values for all genes tested in both control cells and
      siSLC25A10 cells upon metformin treatment. The gene expression of the metabolic
      regulator glutamic-oxaloacetic transaminase 1 decreased in wild type cells upon
      metformin treatment whereas there was a trend of increased expression in the
      siSLC25A10 cells upon metformin treatment. In addition, the gene expression of
      the cyclin-dependent kinase inhibitor 1A was markedly increased in the siSLC25A10
      compared to control A549 cells, and with even larger increases in the presence of
      metformin and at low glucose concentration. Our data show that in siSLC25A10 cell
      lines, metformin significantly alters the SLC25A10 carrier at both mRNA and
      protein levels and can thereby affect the supply of nutrients and the metabolic
      state of cancer cells.

PMID- 30222971
TI  - Increasing adenoma detection rates in the right side of the colon comparing
      retroflexion with a second forward view: a systematic review.
AB  - BACKGROUND AND AIMS: Right-sided lesions are often missed during standard
      colonoscopy (SC). A second forward-view examination or retroflexion in the right
      side of the colon have both been proposed as techniques to improve ADR in the
      right side of the colon. Comparative data on examining the right side of the
      colon with a second forward view or retroflexion is not known in a pooled
      analysis. We performed a systematic review of the literature to assess the yield
      of a second forward view compared with retroflexion examination for the detection
      of right-sided adenomas. METHODS: A systematic literature search was performed
      using the following databases: PubMed, Embase, Web of Science, and Cochrane. Only
      full-length published articles that provided information on adenoma detection and
      miss rates during either a second forward view or retroflexed view of the right
      side of the colon after the initial standard forward withdrawal (SC) were
      included. The following outcomes were assessed: comparison of adenoma miss rate
      (AMR) for second forward view versus retroflexion after SC, AMR of SC compared
      with second forward view, AMR of SC compared with retroflexion, and right-sided
      adenoma detection with second forward view and retroflexion. Pooled rates were
      reported as risk difference or odds ratios (OR) with 95% confidence intervals
      (CI) with a P value <.05 indicating statistical significance. Statistical
      analysis was performed with Review Manager v5.3. RESULTS: We identified 4 studies
      with 1882 patients who underwent a second forward view of the right side of the
      colon after an initial SC. The average age of the patients was 58.3 years. Data
      on right-sided ADR were available from all 4 studies for the second forward view;
      however, only 2 of the studies provided information on right-sided ADR with
      retroflexion. The pooled estimate of AMR of a single SC was 13.3% (95% CI, 6.6%
      20%) compared with a second forward-view examination (n = 4), whereas it was 8.1%
      (3.7%-12.5%) compared with a retroflexion examination (n = 3). However, when the
      second forward view was compared with retroflexion in terms of AMR from an
      analysis of 3 eligible studies, there was no statistically significant difference
      (7.3% vs 6.3%; pooled OR, 1.2; 95% CI, 0.9-1.61; P = .21). Second forward view of
      the right side of the colon increased the right-sided ADR by 10% (n = 4; second
      forward view vs SC, 33.6% vs 26.7%) with a pooled risk difference of 0.09 (95%
      CI, 0.03-0.15; P < .01). Retroflexion increased the right-sided ADR by 6% (n = 3;
      retroflexion vs SC, 28.4% vs 22.7%) with a pooled risk difference of 0.06 (95%
      CI, 0.03-0.09; P < 01). CONCLUSION: After SC withdrawal, a second forward view
      and retroflexed view of the right side of the colon are both associated with
      improvement in ADR. One of these techniques should be considered during SC to
      increase ADR and to improve the quality of colonoscopy.

PMID- 30222972
TI  - Phase 1 study of EUS-guided photodynamic therapy for locally advanced pancreatic
      cancer.
AB  - BACKGROUND AND AIMS: Locally advanced pancreatic cancer (LAPC) has a poor
      prognosis. There are limited data describing the use of photodynamic therapy
      (PDT) for pancreatic cancer in humans. We hypothesized that EUS-guided PDT for
      LAPC is safe, technically feasible, and produces a dose- and time-dependent
      increasing degree of image-defined tumor necrosis. METHODS: In a single-center,
      prospective, dose-escalation phase 1 study, patients with treatment-naive LAPC
      received intravenous porfimer sodium (Concordia Laboratories Inc, St Michael,
      Barbados) followed 2 days later by EUS-PDT. EUS-PDT was performed by puncture
      with a 19-gauge needle and insertion of a 1.0-cm light diffuser (Pioneer Optics,
      Bloomfield, Conn) and illumination with a 630-nm light (Diomed Inc, Andover,
      Mass). A CT scan 18 days after PDT was done to assess for change in pancreatic
      necrosis. Nab-paclitaxel (125 mg/ m2 intravenously) and gemcitabine (1000 mg /m2
      intravenously) were initiated 7 days after CT and given weekly for 3 of 4 weeks
      (1 cycle) until disease progression or unacceptable toxicity. RESULTS: Twelve
      patients (mean age, 67 +/- 6 years; 8 male) with tumors (mean diameter, 45.2 +/-
      12.9 mm) in the head and/or neck (8) or body and/or tail (4) underwent EUS-PDT.
      Compared with baseline imaging, increased volume and percentage of tumor necrosis
      were observed in 6 of 12 patients (50%) after EUS-PDT. The mean overall increases
      in volume and percentage necrosis were 10 +/- 26 cm3 (P = .20) and 18% +/- 22% (P
      = .016), respectively. After a median follow-up of 10.5 months (range, 1.0-37.4
      months), median progression-free (PFS) and overall survival (OS) were 2.6 months
      (95% confidence interval, 0.7, not estimable) and 11.5 months (95% confidence
      interval, 1.1, 16.9), respectively. Surgical resection was attempted in 2
      patients, and pathology showed a complete response (n = 1) and residual 2-mm
      tumor (n = 1). There were 8 serious adverse events and none related to EUS or EUS
      PDT. CONCLUSION: EUS-PDT for LAPC appears to be safe and produces measurable
      imaged-defined tumor necrosis. Phase 2 studies are warranted. (Clinical trial
      registration number: NCT01770132.).

PMID- 30222973
TI  - Temperature triggering of kinetically trapped self-assemblies in citrem
      phospholipid nanoparticles.
AB  - Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles are attractive
      nanocarriers for drug delivery, particularly for the solubilization of poorly
      water-soluble drugs. Due to the reported problems of complement activation and
      cytotoxicity of most investigated Pluronic F127-stabilized cubosomes and
      hexosomes, there is an interest in introducing safe stabilizers for these LLC
      nanodispersions. Citrem appears to be the stabilizer of choice for the colloidal
      stabilization of these LLC nano-self-assemblies owing to its hemocompatiblity and
      poor activation of the complement system. This anionic food-grade emulsifier in
      combination with soy phosphatidylcholine (SPC) can be used to introduce a library
      of hemocompatible lamellar and non-lamellar liquid crystalline nanodispersions at
      different lipid compositions. We found that batch-to-batch variability in citrem
      composition is associated with slight alterations in the size, structural
      characteristics, and surface charge of the produced citrem/SPC nanoparticles.
      Further, we report on the temperature-triggered alterations in these nano-self
      assemblies at different lipid compositions by using synchrotron small angle X-ray
      scattering (SAXS). The addition of citrem at different temperatures induces
      lamellar to non-lamellar structural transitions as evident from the appearance of
      inverse bicontinuous cubic Pn3m and discontinuous hexagonal (H2) phases,
      respectively, upon increasing citrem concentration and varying temperature in the
      range of 5-59  degrees C. Citrem/SPC nanoparticles are attractive for use in the
      development of nanocarriers for drug delivery owing to their structural
      tunability and hemocompatiblity.

PMID- 30222974
TI  - Reorganization of platelet membrane sphingomyelins by adenosine diphosphate and
      ticagrelor.
AB  - Platelets are major targets for the treatment of thrombo-embolic disorders. Their
      plasma membrane contains specialized microdomains enriched in sphingomyelins and
      free cholesterol including membrane receptors. P2Y12 receptors need to be
      situated in these domains to be able to conduct activation signaling by adenosine
      diphosphate (ADP). We studied the impact of ticagrelor, a P2Y12 antagonist, and
      ADP on the composition and distribution of sphingomyelins in detergent-resistant
      membrane (DRM) of platelet membranes. Platelets were obtained from healthy
      donors. DRMs of platelet membranes were isolated in 4 experimental groups:
      control; ADP, with platelets stimulated by 20 MUM ADP and 5 mM CaCl2; ticagrelor,
      with platelets incubated by ticagrelor 4 MUM methanol dissolved; and ticagrelor +
      ADP, with incubation by ticagrelor followed by stimulation by ADP as above. After
      mass spectrometry analysis, we found 16 species of sphingomyelins in platelet
      membrane DRMs. We also found that treatment with ticagrelor and stimulation by
      ADP could induce changes in the composition, distribution and concentration of
      sphingomyelins in membranes of platelets. In all groups, the predominant species
      of sphingomyelins in platelet membrane was d18:1/16:0. Taken together, our
      results show that stimulation by ADP or inhibition by ticagrelor changed the
      level and composition of sphingomyelins in platelet membranes. These changes
      might be considered as reorganization or new recruitment of certain types of
      sphingomyelins through the membrane.

PMID- 30222975
TI  - Interaction of the beta amyloid - Abeta(25-35) - peptide with zwitterionic and
      negatively charged vesicles with and without cholesterol.
AB  - The interactions of the Alzheimer's beta-amyloid peptide, Abeta(25-35), with 18:1
      (Delta9-Cis) PC 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), L-alpha
      phosphatidylcholine (EPC), 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol)
      (sodium salt) (DOPG), and L-alpha-phosphatidylglycerol (EPG) phospholipid
      vesicles with and without cholesterol (Ch) are studied by the nitroxide spin
      probe electron paramagnetic resonance (EPR) method. Two nitroxide spin probes,
      2,2,6,6-tetramethyl-piperidin-1-oxyl-4-yl hexadecanoate (TP, TEMPO-Palmitate) and
      2-Ethyl-2-(15-methoxy-15-oxopentadecyl)-4,4-dimethyl-3-oxazolidinyloxy (16-DSE),
      are utilized in the study. TEMPO-Palmitate has the reporting EPR moiety located
      at the top of this spin probe, while 16-DSE has the reporting EPR moiety located
      at the tail of the spin probe. These two probes enable us to sample the surface
      and the middle of the phospholipid bilayer, respectively. All EPR measurements
      are done above the melting points of all four phospholipids when the bilayer is
      in the liquid crystal phase, the physiologically relevant phase. Due to non
      linear spectral line fitting, the EPR spectral parameters are extracted with high
      precision. The results show that there are two populations of Abeta(25-35) and
      that one of them is located in the hydrophobic phospholipid layer below the
      hydrophilic headgroup region. The second population appears to be weakly coupled
      to the surface of the bilayer. Both hydrophobic and electrostatic interactions
      affect the insertion of Abeta(25-35) in the bilayer. Also, there is strong
      evidence for an interaction between cholesterol and Abeta(25-35), which affects
      the dielectric and dynamic properties of the bilayer.

PMID- 30222976
TI  - Designing the Optimal Formulation for Biopharmaceuticals: A New Approach
      Combining Molecular Dynamics and Experiments.
AB  - Biopharmaceuticals are often stored in a lyophilized form. However, stresses due
      to both the freezing and the drying steps of the lyophilization process can be
      harmful to protein stability, and appropriate excipients must be added to
      minimize detrimental effects. In this work, Molecular Dynamics (MD) was used to
      provide insight into the mechanisms of protein stabilization by different
      osmolytes, using lactate dehydrogenase (LDH) as model protein. Our simulations
      indicate that good cryoprotectants are not always equally good as lyoprotectants,
      suggesting that synergistic effects may arise when different excipients are
      combined. This observation is in accordance with the experimental results. In
      fact, the enzymatic activity of LDH after freeze-drying was investigated for
      various formulations, and the trend predicted by MD was confirmed. More
      specifically, we found that the most effective stabilization of the protein
      structure is achieved when a good cryoprotectant is coupled with an efficient
      lyoprotectant. Ultimately, we propose a new approach to the design of
      formulations for protein-based therapeutics to be lyophilized, which combines
      simulations and experiments. In this new concept, the computational investigation
      allows a more knowledge-driven and targeted experimental campaign for the
      selection of the optimal excipients, making the whole process extremely time and
      cost effective.

PMID- 30222977
TI  - Effect of different tensoactives on the morphology and release kinetics of PLA-b
      PEG microcapsules loaded with the natural anticancer compound perillyl alcohol.
AB  - Perillyl alcohol (POH) is a natural compound that has attracted a significant
      interest due to its potent antitumor activity. However, clinical trials have
      exhibited poor tolerance by oral administration, mainly due to gastrointestinal
      side effects. We propose the entrapment of POH into poly(D,L-lactic acid)-block
      poly(ethylene glycol) (PLA-b-PEG) as delivery platform (entrapment efficiency of
      63 - 68%). The influence of different concentrations of the tensoactives
      poly(vinyl alcohol) (PVAl) and sodium cholate (SC) on shear strength and
      morphology was evaluated by confocal laser scanning microscopy and interfacial
      tension studies. Only the microcapsules formulated with SC maintained their
      sphericity when submitted to shear stress. These results indicate that the
      interface is better organized with SC, conferring mutual stacked packing that is
      able to better stabilize the organic drop. The in vitro release profile of the
      drug from the microcapsules was correlated with pore formation and polymer
      degradation, best fitted to the Baker-Lonsdale model. The loaded microcapsules
      showed an IC50 equivalent to that of the free drug (80 MUg/mL) after 72 h of
      exposure. However, after 24 h of exposure, loaded microcapsules showed an IC50
      almost two-fold higher (220 MUg/mL) suggesting gradual release.

PMID- 30222978
TI  - Application of the Tissue Composition-Based Model to Minipig for Predicting the
      Volume of Distribution at Steady State and Dermis-to-Plasma Partition
      Coefficients of Drugs Used in the Physiologically Based Pharmacokinetics Model in
      Dermatology.
AB  - The minipig continues to build a reputation as a viable alternative large animal
      model to predict humans in dermatology and toxicology studies. Therefore, it is
      essential to describe and predict the pharmacokinetics in that species to speed
      up the clinical candidate selection. Essential input parameters in whole-body
      physiologically based pharmacokinetic models are the tissue-to-plasma partition
      coefficients and the resulting volume of distribution at steady-state (Vss).
      Mechanistic in vitro- and in silico-based models used for predicting these
      parameters of tissue distribution of drugs refer to the tissue composition-based
      model (TCM). Robust TCMs were initially developed for some preclinical species
      (e.g., rat and dog) and human; however, there is currently no model available for
      the minipig. Therefore, the objective of this present study was to develop a TCM
      for the minipig and to estimate the corresponding tissue composition data. Drug
      partitioning into the tissues was predominantly governed by lipid and protein
      binding effects in addition to drug solubilization and pH gradient effects in the
      aqueous phase on both sides of the biological membranes; however, some more
      complex tissue distribution processes such as drug binding to the collagen
      laminin material in dermis and a restricted drug partitioning into membranes of
      tissues for compounds that are amphiphilic and contain sulfur atom(s) were also
      challenged. The model was validated by predicting Vss and the dermis-to-plasma
      partition coefficients (Kp-dermis) of 68 drugs. The prediction of Kp-dermis was
      extended to humans for comparison with the minipig. The results indicate that the
      extended TCM provided generally good agreements with observations in the minipig
      showing that it is also applicable to this preclinical species. In general, up to
      86% and 100% of the predicted Vss values are respectively within 2-fold and 3
      fold errors compared to the experimentally determined values, whereas these
      numbers are 78% and 94% for Kp-dermis when the anticipated outlier compounds are
      not included. Binding data to dermis are comparable between minipigs and humans.
      Overall, this study is a first step toward developing a mechanistic TCM for the
      minipig, with the aim of increasing the use of physiologically based
      pharmacokinetic models of drugs for that species in addition to rats, dogs, and
      humans because such models are used in preclinical and clinical transdermal
      studies.

PMID- 30222979
TI  - Quinone and nitrofurantoin redox cycling by recombinant cytochrome b5 reductase.
AB  - NADH cytochrome b5 reductase mediates electron transfer from NADH to cytochrome
      b5 utilizing flavin adenine dinucleotide as a redox cofactor. Reduced cytochrome
      b5 is an important cofactor in many metabolic reactions including cytochrome P450
      mediated xenobiotic metabolism, steroid biosynthesis and fatty acid metabolism,
      hemoglobin reduction, and methionine and plasmalogen synthesis. Using recombinant
      human enzyme, we discovered that cytochrome b5 reductase mediates redox cycling
      of a variety of quinones generating superoxide anion, hydrogen peroxide, and, in
      the presence of transition metals, hydroxyl radicals. Redox cycling activity was
      oxygen-dependent and preferentially utilized NADH as a co-substrate; NADH was 5
      10 times more active than NADPH in supporting redox cycling. Redox cycling
      activity was greatest for 9,10-phenanthrenequinone and 1,2-naphthoquinone,
      followed by 1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone (menadione),
      nitrofurantoin and 2-hydroxyestradiol. Using menadione as the substrate, quinone
      redox cycling was found to inhibit reduction of cytochrome b5 by cytochrome b5
      reductase, as measured by heme spectral changes in cytochrome b5. Under anaerobic
      conditions where redox cycling is inhibited, menadione had no effect on the
      reduction of cytochrome b5. Chemical redox cycling by cytochrome b5 reductase may
      be important in generating cytotoxic reactive oxygen species in target tissues.
      This activity, together with the inhibition of cytochrome b5 reduction by redox
      active chemicals and consequent deficiencies in available cellular cytochrome b5,
      are likely to contribute to tissue injury following exposure to quinones and
      related redox active chemicals.

PMID- 30222980
TI  - Montelukast attenuates rotenone-induced microglial activation/p38 MAPK expression
      in rats: Possible role of its antioxidant, anti-inflammatory and antiapoptotic
      effects.
AB  - Montelukast (MK),a cysteinyl leukotriene (CysLT1) receptor antagonist, latterly
      exhibited a remarkable neuroprotective activity in various neurodegenerative
      disorders. This study aims to elucidate the neuroprotective effect of MK in
      rotenone-induced Parkinson's disease(PD) model in rats. Ninety six male rats were
      split into four groups: vehicle control (0.2 ml/kg/48 h, sc), MK (10 mg/kg/day,
      ip), rotenone (1.5 mg/kg/48 h, sc.) and rotenone pretreated with MK. Rotenone
      treatment led to significant reduction in motor functioning and elevation in
      oxidative stress markers. Additionally, upregulation of p38 mitogen-activated
      protein kinase (p38 MAPK) and CysLT1 receptor expressions were anchored with
      enhanced striatal microglial activation generating a severe neuro-inflammatory
      milieu. Furthermore, an augmentation in p53 expression and cleaved caspases-3
      activity increased apoptotic neurodegeneration synchronized with reduction of
      striatal tyrosine hydroxylase (TH) content. Changes in neuronal morphology was
      also noted. MK administration significantly mitigated motor impairment and rise
      in oxidative stress mediators. As well, the anti-inflammatory activity of MK was
      manifested by hindering the principal controller of inflammatory pathway, nuclear
      factor-kappa B, followed by its downstream pro-inflammatory cytokines (tumor
      necrosis factor-alpha and interleukin-1 beta), by attenuating striatal microglial
      activation and hampering the expression of both p38 MAPK and CysLT1. Moreover, MK
      revealed a decline in p53 expression with its downstream cleaved caspases-3 which
      resulted in preservation of striatal TH terminals as verified by increased
      striatal TH content and improvement in the histopathological changes incited by
      rotenone. In conclusion, MK endowed neuroprotective effects in rotenone-induced
      PD animal model via attenuation of microglial cell activation and p38 MAPK
      expression.

PMID- 30222981
TI  - Met-enkephalin improves metabolic syndrome in high fat diet challenged mice
      through promotion of adipose tissue browning.
AB  - Obesity and its related metabolic disorders including insulin resistance and
      fatty liver become major public health concerns in both developed and developing
      countries. Brown adipose tissue (BAT), a critical organ of energy expenditure due
      to thermogenesis, has been considered as an attractive target for prevention or
      treatment of obesity and obesity related diseases. Previous studies indicate Met
      enkephalin (MetEnk) has the potential on adipocyte browning, however, whether
      MetEnk displays the impact on adipocyte browning in vivo to improve obesity
      associated morbidities is still unclear. In the present study, we showed that
      MetEnk effectively prevented high fat diet (HFD) induced C57BL/6J mice weight
      gain, clearly enhanced glucose tolerance and insulin sensitivity, and
      dramatically reduced hepatic steatosis in HFD fed mice. Mechanically, MetEnk
      restored protein kinase A (PKA) signaling pathway in HFD challenged mice and
      promoted subcutaneous white adipose tissue (WAT) browning. Our study suggests
      that MetEnk can be considered as a potential therapeutic peptide for diet-induced
      obesity and metabolic disorders.

PMID- 30222982
TI  - Development of a novel progesterone analog in the treatment of traumatic brain
      injury.
AB  - Although systemic progesterone (PROG) treatment has been shown to be
      neuroprotective by many laboratories and in multiple animal models of brain
      injury including traumatic brain injury (TBI), PROG's poor aqueous solubility
      limits its potential for use as a therapeutic agent. The problem of solubility
      presents challenges for an acute intervention for neural injury, when getting a
      neuroprotectant to the brain quickly is crucial. Native PROG (nPROG) is
      hydrophobic and does not readily dissolve in an aqueous-based medium, so this
      makes it harder to give under emergency field conditions. An agent with
      properties similar to those of PROG but easier to store, transport, formulate,
      and administer early in emergency trauma situations could lead to better and more
      consistent clinical outcomes following TBI. At the same time, the engineering of
      a new molecule designed to treat a complex systemic injury must anticipate a
      range of translational issues including solubility and bioavailability. Here we
      describe the development of EIDD-1723, a novel, highly stable PROG analog with
      >104-fold higher aqueous solubility than that of nPROG. We think that, with
      further testing, EIDD-1723 could become an attractive candidate use as a field
      ready treatment for TBI patients.

PMID- 30222983
TI  - Riluzole attenuates the efficacy of glutamatergic transmission by interfering
      with the size of the readily releasable neurotransmitter pool.
AB  - Riluzole is a potent neuroprotective agent which primarily inhibits excitatory
      neurotransmission interfering with presynaptic release, uptake and postsynaptic
      actions of glutamate by mechanisms that are not well understood. Riluzole and
      related prodrugs with improved blood brain barrier penetrance, are shown to be
      effective for the treatment of amyotrophic lateral sclerosis, ataxias, epilepsy
      and mood disorders. Our study was undertaken to decipher molecular and
      subcellular mechanisms of riluzole's antiglutamatergic effect, particularly
      focusing on presynaptic active zone structure and function. Applying multifarious
      live cell imaging techniques and amperometric glutamate recordings, we measured
      the impact of riluzole on presynaptic activity, synaptic vesicle recycling and
      glutamate release. Our in vitro and in vivo data revealed a unique mechanism
      whereby riluzole reduces the efficacy of glutamatergic transmission by
      selectively lowering the size of the readily releasable pool. This effect was
      correlated with the inhibition of protein kinase C-dependent Munc18-1
      phosphorylation which is known to interfere with neurotransmitter release.

PMID- 30222984
TI  - TBI Rehabilomics Research: Conceptualizing a humoral triad for designing
      effective rehabilitation interventions.
AB  - Most areas of medicine use biomarkers in some capacity to aid in understanding
      how personal biology informs clinical care. This article draws upon the
      Rehabilomics research model as a translational framework for programs of
      precision rehabilitation and intervention research focused on linking personal
      biology to treatment response using biopsychosocial constructs that broadly
      represent function and that can be applied to many clinical populations with
      disability. The summary applies the Rehabilomics research framework to the
      population with traumatic brain injury (TBI) and emphasizes a broad vision for
      biomarker inclusion, beyond typical brain-derived biomarkers, to capture and/or
      reflect important neurological and non-neurological pathology associated with TBI
      as a chronic condition. Humoral signaling molecules are explored as important
      signaling and regulatory drivers of these chronic conditions and their impact on
      function. Importantly, secondary injury cascades involved in the humoral triad
      are influenced by the systemic response to TBI and the development of non
      neurological organ dysfunction (NNOD). Biomarkers have been successfully
      leveraged in other medical fields to inform pre-randomization patient selection
      for clinical trials, however, this practice largely has not been utilized in TBI
      research. As such, the applicability of the Rehabilomics research model to
      contemporary clinical trials and comparative effectiveness research designs for
      neurological and rehabilitation populations is emphasized. Potential points of
      intervention to modify inflammation, hormonal, or neurotrophic support through
      rehabilitation interventions are discussed.

PMID- 30222985
TI  - Reply to: "Risk of skin cancer in HIV-infected patients: a Danish nationwide
      cohort study".

PMID- 30222986
TI  - Use of Immortal time within survival analysis.

PMID- 30222987
TI  - Clobetasol pretreatment to reduce or prevent injection site dermatitis from
      biologic agents.

PMID- 30222988
TI  - Answer to the comment concerning our article "Risk of skin cancer in HIV-infected
      patients: a Danish nationwide cohort study".

PMID- 30222989
TI  - Orexin 1 receptors in the anterior cingulate and orbitofrontal cortex regulate
      cost and benefit decision-making.
AB  - Orexin neurons are discretely localized within the lateral hypothalamus and have
      widespread projections into all areas of the brain. In addition, several lines of
      evidence specify that orexins may also participate in the regulation of a variety
      of affective and cognitive processes. The Orexin-1 receptor (OX1r) is distributed
      extensively throughout the prefrontal cortex (PFC). Delay-based decision- making
      is mediated largely by the orbitofrontal cortex (OFC) while effort- based
      decision-making is controlled by the anterior cingulated cortex (ACC). Hence, in
      the present study, a series of experiments were conducted to clarify the role of
      OX1r in the mPFC (ACC and/or OFC) in cost and benefit decision-making. The rats
      were trained in a delay and/or effort-based form of cost-benefit T-maze decision
      making task. Two goal arms were different in the amount of accessible reward and
      cost. Before surgery, all animals were selecting the high reward arm and pay the
      cost on almost every trial. During the test days, the rats received local
      injections of either DMSO 20% /0.5 MUl, as a vehicle, or SB334867 (3, 30 and 300
      nM/0.5 MUl), as a selective OX1r antagonist, within the ACC and/or OFC. The
      results of this study showed that the bilateral microinjection of SB334867 into
      ACC and/or OFC changed the preference to a low reward arm with no cost,
      indicating the role of OX1 receptors in cost and benefit decision- making. From
      these results, it can be implied that OX1 receptors in the mPFC play a crucial
      role for allowing the animal to evaluate and pay the cost to acquire greater
      rewards.

PMID- 30222990
TI  - Development and evaluation of a droplet digital PCR assay for the detection of
      fowl adenovirus serotypes 4 and 10 in attenuated vaccines.
AB  - In recent years, there has been an increase in reported cases of fowl adenovirus
      serotype 4 (FAdV-4) in chickens in China. The use of live attenuated vaccines
      contaminated with FAdV-4 has been proved to be one of the important causes of
      massive outbreaks of hydropericardium syndrome. To detect the contamination with
      FAdV-4 in attenuated vaccines more promptly and accurately, a droplet digital PCR
      (ddPCR) assay was developed for the rapid detection of FAdV-4 and FAdV-10. The
      ability of this assay to detect FAdV-4 contamination in attenuated Newcastle
      disease virus vaccines was assessed in comparison to a quantitative real-time PCR
      (qPCR) and a conventional PCR assay. The findings indicated that the ddPCR assay
      could detect FAdV-4 contamination at 0.1 EID50/1,000 feathers, while the qPCR
      could detect FAdV-4 contamination at 1 EID50/1,000 feathers with identical
      genomic targets, which was 1,000-fold more sensitive than conventional PCR
      detection with a sensitivity of 102 EID50/1,000 feathers. The ddPCR assay also
      showed high specificity for FAdV-4/10 and no positive signals were detected for
      other FAdVs. Consequently, the intuitive and rapid results were especially
      suitable for the detection of FAdV-4 contamination in vaccines. In this study, a
      ddPCR assay was developed to effectively detect and quantify low-dose FAdV-4
      contamination, providing a new method for rapid detection of FAdV-4 contamination
      in various samples, especially vaccines.

PMID- 30222991
TI  - Pediatric acute-onset neuropsychiatric syndrome (PANS) misdiagnosed as autism
      spectrum disorder.

PMID- 30222992
TI  - Two ways for interpreting Driesch's law: "Positional information" and
      morphogenetic fields.
AB  - The late Lev V. Beloussov wrote a 2005 textbook The Foundations of General
      Embryology which is available in Russian. In 2003 he prepared an excellent,
      annotated translation of the part of his manuscript for this book on
      distinguishing positional information models from morphogenetic field models of
      embryogenesis, which is reproduced here verbatim. He concluded: "...the PI
      [positional information] concept has no predictive value, and cannot be thus
      regarded as a scientific theory".

PMID- 30222993
TI  - On symmetries, resonances and photonic crystals in morphogenesis.
AB  - Biological symmetries, theories of the morphogenetic field, resonant interactions
      and the role of photons in morphogenetic processes represented the main fields of
      interest of Lev Beloussov and his followers. This review article includes some
      results of our study on the important role of resonances and photonic crystals in
      genetic informatics. Mathematical formalisms of differential Riemannian geometry
      and tensor analysis are used for modeling inherited curved surfaces in
      biomorphology and for understanding conformal bio-symmetries connected with the
      networks of curvature lines of surfaces. Notions of a morpho-resonance field as
      one of variants of morphogenetic fields are discussed. The connection of the
      golden section with the Fibonacci matrix of growth used in morphogenetic models
      of phyllotaxis is shown. Photonic crystals are considered as important
      participants of organisation of molecular-genetic informatics.

PMID- 30222994
TI  - Comparison Between Thulium Laser VapoEnucleation and GreenLight Laser
      Photoselective Vaporization of the Prostate in Real-Life Setting: Propensity
      Score Analysis.
AB  - OBJECTIVE: To compare in daily practice efficacy and safety of standard 180-Watt
      GreenLight laser photoselective vaporization (PVP) and Thulium laser
      Vaporesection of the prostate (ThuVEP). MATERIALS AND METHODS: All men were
      evaluated with prostate volume, prostate-specific antigen, International Prostate
      Symptom Score, and maximum urinary flow. Patient global impression of improvement
      was evaluated with patient global impression of improvement scale for 6 months.
      Antiplatelet/anticoagulant therapy, operation time, 24-hour hemoglobin drop ,
      length of catheterization, discharge day, early complications, and reoperation
      after 30 days were gathered. Differences between interventions were estimated
      using propensity scores to adjust for different patients characteristics. The
      propensity scores were estimated by fitting a stepwise logistic regression model
      with intervention type as the dependent variable and all the covariates. RESULTS:
      Five hundred five men underwent the surgical procedures (291 PVP and 214 ThuVEP).
      Mean age was 69.6 years. Mean prostate volume was 54 mL. Median operation time
      was 55 minutes. Median catheterization time was 2 days in both series. After
      matching, the postoperative stay was similar in both groups (2 days). Hemoglobin
      drop for 24 hours was statistically significantly lower in PVP (-0.5 vs -0.8
      g/dL, P .002). Most of the complications were mild-to-moderate and comparable
      among groups. Delta Maximum urinary flow was similar 6-month after surgery before
      and after matching, whereas PVP group had a better improvement 12-month after
      surgery. 96.4% of all patients had an improvement of their symptoms, with no
      difference between groups, before and after matching. CONCLUSION: Our study
      demonstrated that PVP and ThuVEP are similar in term of complications and
      outcomes, with high patients' satisfaction.

PMID- 30222995
TI  - Rates and Risk Factors for Future Stress Urinary Incontinence Surgery after
      Pelvic Organ Prolapse Repair in a Large Population-based Cohort in California.
AB  - OBJECTIVES: To determine the rate and risk factors for future stress urinary
      incontinence (SUI) surgery in a large population-based cohort of previously
      continent women following pelvic organ prolapse (POP) repair without concomitant
      SUI treatment. METHODS: Data from the Office of Statewide Health Planning and
      Development were used to identify all women who underwent anterior, apical, or
      combined anteroapical POP repair without concomitant SUI procedures in the state
      of California between 2005 and 2011 with at least 1-year follow-up. Patient and
      surgical characteristics were explored for associations with subsequent SUI
      procedures. RESULTS: Of 41,689 women undergoing anterior or apical POP surgery,
      1,504 (3.6%) underwent subsequent SUI surgery with a mean follow-up time of 4.1
      years. Age (odds ratio [OR] 1.01), obesity (OR 1.98), use of mesh at the time of
      POP repair (OR 2.04), diabetes mellitus (OR 1.19), white race, and combined
      anteroapical repair (OR 1.30) were associated with increased odds of future SUI
      surgery. CONCLUSION: The rate of subsequent surgery for de novo SUI following POP
      repair on a population level is low. Patient and surgical characteristics may
      alter a woman's individual risk and should be considered in surgical planning.

PMID- 30222996
TI  - Changes in VIP-, SP- and CGRP- like immunoreactivity in intramural neurons within
      the pig stomach following supplementation with low and high doses of acrylamide.
AB  - Acrylamide is one of the food toxins to which the human body is exposed. Although
      researchers' interest in acrylamide has been growing in recent years, the
      knowledge of its effect on the gastrointestinal tract, especially on intramural
      neurons which form the enteric nervous system is scarce. The aim of this
      experiment was to determine the influence of acrylamide, administered at doses
      equivalent to the human tolerable daily intake (TDI, 0.5 MUg/kg b.w./day) and ten
      times higher than the TDI (5 MUg/kg b.w./day), on the distribution of vasoactive
      intestinal peptide (VIP), substance P (SP), and calcitonin gene related peptide
      (CGRP) in intramural neurons of the domestic pig stomach. Using double
      immunofluorescent labelling we revealed that the ENS neurons underwent adaptive
      changes in response to the supplementation of acrylamide, which manifested
      themselves as increased expression of VIP, SP and CGRP, both in intramural
      neurons and by an increase in the nerve density in submucous and muscular layers
      in the porcine stomach. These substances take part in defensive reactions of
      neurons and transmission of sensory reactions may play an important role in
      protecting the stomach against the harmful effect of acrylamide. Moreover, it has
      been shown that acrylamide induces a significant response of ENS neurons even in
      TDI dose, which suggests that it is not neutral to the body. These findings may
      be the basis for further toxicological studies addressing the question if
      currently permitted minimal content of acrylamide in the food does jeopardize the
      health of human consumers?

PMID- 30222997
TI  - Immunofluorescence/fluorescence assessment of brain-derived neurotrophic factor,
      c-Fos activation, and apoptosis in the brain of zebrafish (Danio rerio) larvae
      exposed to glufosinate.
AB  - In this study, we investigated the potential neuro-toxicological mechanism of the
      glufosinate in the brain of zebrafish larvae in terms of BDNF and c-Fos proteins
      by evaluating apoptosis, immunofluorescence BDNF, and c-FOS activation. We also
      measured survival rate, hatching rate, and body malformations during 96 h
      exposure time. For this purpose, zebrafish embryos were treated with graded
      concentrations of dosing solutions (0.5, 1, 3, and 5 ppm) of glufosinate. End of
      the treatment, acridine orange staining was used to detect apoptotic cells in the
      brain of zebrafish larvae at 96 hpf. Texas Red and FITC/GFP labeled protein
      specific antibodies were used in immunofluorescence assay for BDNF and c-FOS,
      respectively. The results have indicated that exposure to glufosinate caused to
      embryonic death, hatching delay, induction of apoptosis, increasing of c-FOS
      activity and the level of BDNF in a dose-dependent manner. As a conclusion, we
      suggested that c-Fos might play a role in the regulation of BDNF which responses
      to prevent the cell from apoptosis even in case of unsuccessful in zebrafish
      larvae exposed to glufosinate.

PMID- 30222999
TI  - 4D imaging identifies dynamic migration and the fate of gbx2-expressing cells in
      the brain primordium of zebrafish.
AB  - One of the pivotal events in neural development is compartmentalization, wherein
      the neural tissue divides into domains and undergoes functional differentiation.
      For example, midbrain-hindbrain boundary (MHB) formation and subsequent isthmus
      development are key steps in cerebellar development. Although several regulatory
      mechanisms are known to underlie this event, little is known about cellular
      behaviors. In this study, to examine the cellular dynamics around the MHB region,
      we performed confocal time-lapse imaging in zebrafish embryos to track cell
      populations in the neural tube via 4D analysis. We used a transgenic line wherein
      enhanced green fluorescent protein (EGFP) expression is driven by the
      gastrulation brain homeobox 2 (gbx2) enhancer, which is involved in MHB
      maintenance. 4D time-lapse imaging of 5-20 h revealed a novel pattern in cell
      migration: a dynamic ventrocaudally directed migration from the MHB region toward
      the hindbrain. Furthermore, in the hindbrain region, these EGFP-positive cells
      altered their shapes and extended the axons. Immunohistochemical analysis and
      retrograde labeling showed that these cells in the hindbrain were in the process
      of neuronal differentiation, including reticulospinal neurons. These results
      revealed the dynamic and two-step behavior and possible fate of the cell
      population, which are linked to brain compartmentalization, leading to a deeper
      understanding of brain development and formation of neuronal circuits.

PMID- 30222998
TI  - Understanding individual differences in vulnerability to cigarette smoking is
      enhanced by attention to the intersection of common risk factors.
AB  - While smoking prevalence in the U.S. and other industrialized countries has
      decreased substantially, this change has been unevenly distributed, with dramatic
      decreases in certain subpopulations but little change or even increases in
      others. Accordingly, considerable attention has been fruitfully devoted to
      identifying important risk factors for smoking (e.g., mental illness, other
      substance use disorders). However, there has been little research on the
      intersection of these risk factors. As risk factors rarely occur in isolation, it
      is important to examine risk-factor profiles as is commonly done in studying
      other chronic conditions (e.g., cardiovascular disease). The purpose of this
      Commentary is to encourage greater interest in the intersection of multiple risk
      factors using cigarette smoking as an exemplar. We focus on the intersection of
      eight well-established risk factors for smoking (age, gender, race/ethnicity,
      educational attainment, poverty, drug abuse/dependence, alcohol abuse/dependence,
      mental illness). Studying the intersection of risk factors is likely to require
      use of innovative data-analytic methods. We illustrate, using years 2011-2016 of
      the US National Household Survey on Drug Use and Health, how Classification and
      Regression Tree (CART) analysis can be an effective tool for identifying risk
      profiles for smoking. Examination of the intersection of these risk factors
      elucidates a series of risk profiles with associated, orderly gradations in
      vulnerability to current smoking, including the striking and reliable strength of
      a college education as a stand-alone profile predicting low risk for current
      smoking, and illustrating the potentially increasing importance of drug
      abuse/dependence as a risk factor.

PMID- 30223000
TI  - Impairment in exploratory behavior is associated with arc gene overexpression in
      the dorsolateral striatum of rats with nigral injection of l-buthionine
      sulfoximine.
AB  - The aims of the present work were to evaluate the exploratory activity in Sprague
      Dawley rats, as well as to analyze the nigral and striatal mRNA expression of the
      plasticity-related genes bdnf and arc after L-buthionine sulfoximine (BSO)
      injection into substantia nigra compacta. Lesioned rats traveled less distance in
      open field but did not show a decline in the novel object recognition test. On
      the other hand, RT-PCR analysis showed overexpression of striatal arc 24 h post
      lesion; no significant changes in bdnf expression were observed in nigral or
      striatal tissue. These results suggest that intranigral BSO injection causes
      impairment in exploratory behavior in these rats, by affecting locomotion, which
      is associated with changes in striatal synaptic plasticity.

PMID- 30223001
TI  - Single-molecule studies of flavivirus envelope dynamics: Experiment and
      computation.
AB  - Flaviviruses are simple enveloped viruses exhibiting complex structural and
      functional heterogeneities. Decades of research have provided crucial basic
      insights, antiviral medication and moderately successful gene therapy trials. The
      most infectious particle is, however, not always the most abundant one in a
      population, questioning the utility of classic ensemble-averaging virology
      approaches. Indeed, viral replication is often not particularly efficient, prone
      to errors or containing parallel routes. Here, we review different single
      molecule sensitive fluorescence methods that are employed to investigate
      flaviviruses. In particular, we review how (i) time-resolved Forster resonance
      energy transfer (trFRET) was applied to probe dengue envelope conformations; (ii)
      FRET-fluorescence correlation spectroscopy to investigate dengue envelope
      intrinsic dynamics and (iii) single particle tracking to follow the path of
      dengue viruses in cells. We also discuss how such methods may be supported by
      molecular dynamics (MD) simulations over a range of spatio-temporal scales, to
      provide complementary data on the structure and dynamics of flaviviral systems.
      We describe recent improvements in multiscale MD approaches that allowed the
      simulation of dengue particle envelopes in near-atomic resolution. We hope this
      review is an incentive for setting up and applying similar single-molecule
      studies and combine them with MD simulations to investigate structural dynamics
      of entire flavivirus particles over the nanosecond-to-millisecond time-scale and
      follow viruses during infection in cells over milliseconds to minutes.

PMID- 30223002
TI  - Probiotics modify body weight together with anxiety states via pro-inflammatory
      factors in HFD-treated Syrian golden hamster.
AB  - Emerging studies are beginning to suggest that emotional states together with
      healthful measures constitute pertinent features of our lifestyle in which bad
      eating habits but more importantly what our gut has to host are causing great
      concern. It is well known that humans have established mutual relationships with
      a wide array of colonized microbes (collectively called gut microbiota)
      consisting of bacteria, fungi, eukaryotic parasites and viruses. The gut
      microbiota has exhibited a notable ability of communicating with the brain via a
      two-way system that includes the vagus nerve, immune sites, and a number of
      neurotransmitters. Interestingly, stressful along with obesity, cognitive, and
      brain developmental states are strongly influenced by microbiota homeostatic
      conditions. It was our aim to investigate behavioral and obesity effects evoked
      by treatment with probiotics via neuroinflammatory factors and namely IL-1beta,
      NLRP3, Caspase-1 and NF-kB levels in the Syrian golden hamster. Following
      treatment with a high-fat diet (HFD), in the presence or absence of a multi
      species probiotic formulation, hamsters were exposed to an unpredictable chronic
      mild stress (UCMS) test for 4 weeks. Independently of the diet, probiotics
      treatment markedly reduced stress-like behaviors in the different mazes.
      Moreover, probiotics decreased hypothalamic expression levels of the pro
      neuroinflammatory factors like IL-1beta, NLRP3, Caspase-1 and NF-kB, whereas HFD
      increased them. Contextually, they decreased plasmatic levels of IL-1beta, NLRP3
      and caspase-1 but not NF-kB. Our findings clearly support probiotics as a
      potentially valuable treatment strategy in obesity and anxiety, thereby proposing
      them for clinical treatments in patients with metabolic and mood disorders.

PMID- 30223003
TI  - Molecular mechanisms involved in the protective actions of Selective Estrogen
      Receptor Modulators in brain cells.
AB  - Synthetic selective modulators of the estrogen receptors (SERMs) have shown to
      protect neurons and glial cells against toxic insults. Among the most relevant
      beneficial effects attributed to these compounds are the regulation of
      inflammation, attenuation of astrogliosis and microglial activation, prevention
      of excitotoxicity and as a consequence the reduction of neuronal cell death.
      Under pathological conditions, the mechanism of action of the SERMs involves the
      activation of estrogen receptors (ERs) and G protein-coupled receptor for
      estrogens (GRP30). These receptors trigger neuroprotective responses such as
      increasing the expression of antioxidants and the activation of kinase-mediated
      survival signaling pathways. Despite the advances in the knowledge of the
      pathways activated by the SERMs, their mechanism of action is still not entirely
      clear, and there are several controversies. In this review, we focused on the
      molecular pathways activated by SERMs in brain cells, mainly astrocytes, as a
      response to treatment with raloxifene and tamoxifen.

PMID- 30223004
TI  - Elucidating paramylon and other carbohydrate metabolism in Euglena gracilis:
      Kinetic characterization, structure and cellular localization of UDP-glucose
      pyrophosphorylase.
AB  - Many oligo and polysaccharides (including paramylon) are critical in the Euglena
      gracilis life-cycle and they are synthesized by glycosyl transferases using UDP
      glucose as a substrate. Herein, we report the molecular cloning of a gene
      putatively coding for a UDP-glucose pyrophosphorylase (EgrUDP-GlcPPase) in E.
      gracilis. After heterologous expression of the gene in Escherichia coli, the
      recombinant enzyme was characterized structural and functionally. Highly purified
      EgrUDP-GlcPPase exhibited a monomeric structure, able to catalyze synthesis of
      UDP-glucose with a Vmax of 3350 U.mg-1. Glucose-1P and UTP were the preferred
      substrates, although the enzyme also used (with lower catalytic efficiency) TTP,
      galactose-1P and mannose-1P. Oxidation by hydrogen peroxide inactivated the
      enzyme, an effect reversed by reduction with dithiothreitol or thioredoxin. The
      redox process would involve sulfenic acid formation, since no pair of the 7
      cysteine residues is close enough in the 3D structure of the protein to form a
      disulfide bridge. Electrophoresis studies suggest that, after oxidation, the
      enzyme arranges in many enzymatically inactive structural conformations; which
      were also detected in vivo. Finally, confocal fluorescence microscopy provided
      evidence for a cytosolic (mainly in the flagellum) localization of the enzyme.

PMID- 30223005
TI  - An endophytic strain of genus Paenibacillus isolated from the fruits of Noni
      (Morinda citrifolia L.) has antagonistic activity against a Noni's pathogenic
      strain of genus Aspergillus.
AB  - Endophytes are microbes capable of colonizing the tissues of healthy plants and
      subsequently establishing a harmonious relationship with their hosts. In this
      research, the endophytic strain Paenibacillus sp. NEB was isolated from fruits of
      healthy Noni (Morinda citrifolia L.). Strain NEB was identified as Paenibacillus
      polymyxa using MALDI-TOF Mass Spectrometry. Pathogenic fungal strain NP-1 was
      isolated from Noni fruits infected by smut, and was identified as Aspergillus
      aculeatus by polyphasic taxonomy basing on morphological identification, and ITS
      5.8S rDNA and beta-tubulin gene phylogenetic analyses. Through the antagonistic
      test against the pathogenic strain Aspergillus aculeatus NP-1, the results showed
      that strain NEB had a good antagonistic activity against smut pathogen of Noni.
      By sequencing with Illumina HiSeq 2000, the draft genome of Paenibacillus sp. NEB
      was acquired, and 3 CDSs for glucanases were annotated and potentially correlated
      to the antagonistic activity of this strain. Using realtime-PCR method with
      specific primers to amplify the biocontrol gene, beta-1,3-1,4- glucanase gene
      (gluB), it was found in Paenibacillus polymyxa NEB. This study would provide a
      theoretical and microbial basis for the rationally developing and using Noni
      beneficial microbial inoculants against its pathogenic strain in the future.

PMID- 30223006
TI  - The rotating stretched curved planar reconstruction of 3D-FIESTA MR imaging for
      evaluating the anterior cruciate ligament of the knee joint.
AB  - PURPOSE: To determine the feasibility of the rotating stretched curved planar
      reconstruction (CPR) of three-dimensional fast imaging with steady-state
      acquisition magnetic resonance imaging (3D-FIESTA MRI) for evaluating the
      anterior cruciate ligament of the knee joint. MATERIALS AND METHODS: MRI of 40
      knee joints in healthy volunteers was performed on a 3.0-T MR scanner and a
      phased-array extremity coil. The protocol consisted of oblique sagittal spin echo
      (SE) T1WI, coronal FS-PDWI, axial FS-FSE-T2WI, and 3D-FIESTA sequences. The
      rotating stretched curved planar reconstructions (CPR) of the ACL at angles of 0
      degrees , 30 degrees , 60 degrees , 90 degrees , 120 degrees , 150 degrees , and
      180 degrees  were generated from images of 3D-FIESTA sequences. Signal-to-noise
      ratio (SNR) and contrast-to-noise ratio (CNR) of the 3D-FIESTA were compared with
      those of the oblique sagittal SE T1WI sequence. The presence of the tibial
      attachment, midportion, femoral attachment, and double bundles of the ACL on the
      oblique sagittal SE T1WI and CPR of 3D-FIESTA MR imaging were divided into two
      categories: visible and not visible. RESULTS: The ACL SNR efficiency of 3D-FIESTA
      sequences was significantly higher than that of oblique sagittal SE T1WI sequence
      (P < 0.05). The 3D-FIESTA sequences produced images with a significantly higher
      CNR between ACL and synovial fluid than did the oblique sagittal SE T1WI sequence
      (P < 0.05). CPR of 3D-FIESTA MRI generated an excellent visualization of the ACL.
      The CPR of 3D-FIESTA MRI was rated superior to oblique sagittal SE T1WI sequence
      in 60% and 65% of cases with regard to the tibial attachment and midportion of
      ACL, respectively (P < 0.05). CPR of 3D-FIESTA MR imaging was rated superior to
      oblique sagittal SE T1WI sequence in 80% and 85% of cases with regard to femoral
      attachment and double bundles of ACL, respectively (P < 0.05). CONCLUSION: The
      rotating stretched curved planar reconstruction of 3D-FIESTA sequences is
      significantly better than that of conventional 2D-MRI in evaluating the native
      ACL and its components, AM bundle and PL bundle, in healthy volunteers.

PMID- 30223007
TI  - Identification of the splice variants of Recepteur d'Origine nantais (RON) in
      lung cancer cell lines.
AB  - RON receptor tyrosine kinase is a transmembrane protein directly involved in
      suppression of inflammation and its aberrant expression linked to cancers and
      metastasis. Efforts to block deregulated RON signaling in tumors using small
      molecule kinase inhibitors or antibodies have been complicated by the presence of
      unknown number/types of isoforms of RON, which, despite being structurally
      similar, localize differently and mediate varied functions. Current study was
      designed to identify the splice variants of RON transcripts formed by skipping of
      sequences between exons 9 and 14 for better understanding of isoform specific RON
      signaling in cancers. PCR amplification and bi-directional sequencing of a 901 bp
      cDNA sequence located between exons 9 to 14 of RON from lung cancer cell lines
      revealed the presence of two splicing variants formed by skipping of exons 11 and
      11-13. Each of these transcripts was found in more than one cell line. Expressed
      sequence tag (EST) database search indicated that the splicing variant lacking
      exons 11-13 was a novel one. Here we conclude that the splice variants of RON
      lacking exon 11 and exons 11-13 were detected in several lung cancer cell lines.
      Novel variant formed by skipping exons 11-13, the sequence of which code for
      transmembrane region, is predicted to code for a truncated isoform that may be
      secreted out. Tumors may antagonize the ligand dependent anti-inflammatory
      function of wild-type RON by secreting out the ligand binding isoforms.

PMID- 30223008
TI  - The phenotypic and mutational spectrum of Thai female patients with ornithine
      transcarbamylase deficiency.
AB  - Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder
      affecting both males and females. Hemizygous males commonly present with severe
      hyperammonemic encephalopathy during the neonatal period. Heterozygous females
      have great phenotypic variability. The majority of female patients can manifest
      later in life or have unrecognized symptoms, making the diagnosis of OTCD in
      females very challenging. Here we report on three unrelated Thai female cases
      with OTCD presenting with different manifestations including aggressive behavior,
      acute liver failure and severe encephalopathy. Whole exome sequencing
      successfully identified disease-causing mutations in all three cases including
      two novel ones: the c.209_210delAA (p.Lys70Argfs*17) and the c.850T>A
      (p.Tyr284Asn). This study affirms variable symptoms in female patients with OTCD
      and emphasizes the importance of early recognition and prompt management for
      favorable outcomes. In addition, identification of two novel causative variants
      expands the genotypic spectrum of OTC.

PMID- 30223009
TI  - Maternal diet of polyunsaturated fatty acid influence the physical and
      neurobehaviour of rat offspring.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFAs) are normal components of growth
      and development and its derivatives especially n-3 PUFAs have an influence on the
      development and maturation of nervous system. The purpose of our present study
      was to investigate the effect of maternal n-3 PUFAs dietary on physical
      maturation and the neurobiological development of the rat offspring. METHODS:
      According to the content of n-3 PUFAs in their diets, female dams were randomly
      divided into three treatment groups (n = 6-7): deficiency, control and
      supplementation. The physical parameters and neurobehavioral tests were measured
      in the rats' offspring. RESULTS: There were no significant differences in litter
      size and sex ratio between three groups. However, the ratio of brain/body weight
      was higher in the deficiency pups than the control. As to the body weight, the
      deficiency pups were heavier than the control pups on postnatal day (PND) 1,
      PND7, PND14, and PND21, while supplementation pups were lower than the control
      pups on PND1. There are no significant differences in the physical parameters of
      incisor eruption and fur appearance between three groups. However, deficiency
      pups had earlier eye opening than the control pups. Unfortunately, there were no
      significant differences in surface righting reflex, cliff avoidance, forelimb
      grip and air righting reflex. Whereas, supplementation pups required less time to
      complete negative geotaxis than the control pups on PND17. CONCLUSION: This study
      suggests that the consumption of adequate n-3 PUFAs is benefit for the optimal
      growth and development of rat offspring. The n-3 PUFAs supplementation is
      beneficial to population that did not have sufficient provision of n-3 PUFAs in
      the diet during gestation and lactation.

PMID- 30223010
TI  - The complete mitochondrial genome of Sarcoptes scabiei var. nyctereutis from the
      Japanese raccoon dog: Prediction and detection of two transfer RNAs (tRNA-A and
      tRNA-Y).
AB  - Sarcoptes scabiei (Acari: Sarcoptidae) causes a common contagious skin disease
      that affects many mammals. Here, the complete mitochondrial genome of a mite, S.
      scabiei var. nyctereutis, from Japanese wild raccoon dogs was analyzed. The
      13,837bp circular genome contained 13 protein-coding genes, two rRNA genes, and
      22 tRNA genes. For the first time, two tRNAs (alanine and tyrosine), that were
      thought to be absent in scabies mites from other animals, were predicted to have
      short, non-cloverleaf structures by in silico annotation and detected by RT-PCR,
      sequencing, and northern analysis. The mitochondrial genome structure of S.
      scabiei is similar to that of Psoroptes cuniculi and Dermatophagoides farinae.
      While small and unusual tRNA genes seem to be common among acariform mites,
      further experimental evidence for their presence is needed. Furthermore, through
      an analysis of the cox1 gene, we have provided new evidence to confirm the
      transmission of this mite between different animal hosts.

PMID- 30223011
TI  - Brain glial activation in fibromyalgia - A multi-site positron emission
      tomography investigation.
AB  - Fibromyalgia (FM) is a poorly understood chronic condition characterized by
      widespread musculoskeletal pain, fatigue, and cognitive difficulties. While
      mounting evidence suggests a role for neuroinflammation, no study has directly
      provided evidence of brain glial activation in FM. In this study, we conducted a
      Positron Emission Tomography (PET) study using [11C]PBR28, which binds to the
      translocator protein (TSPO), a protein upregulated in activated microglia and
      astrocytes. To enhance statistical power and generalizability, we combined
      datasets collected independently at two separate institutions (Massachusetts
      General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to
      disentangle the contributions of different glial cell types to FM, a smaller
      sample was scanned at KI with [11C]-L-deprenyl-D2 PET, thought to primarily
      reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27
      healthy controls (HC) were examined using [11C]PBR28 PET. 11 FM patients and 11
      HC were scanned using [11C]-L-deprenyl-D2 PET. Standardized uptake values
      normalized by occipital cortex signal (SUVR) and distribution volume (VT) were
      computed from the [11C]PBR28 data. [11C]-L-deprenyl-D2 was quantified using
      lambda k3. PET imaging metrics were compared across groups, and when differing
      across groups, against clinical variables. Compared to HC, FM patients
      demonstrated widespread cortical elevations, and no decreases, in [11C]PBR28 VT
      and SUVR, most pronounced in the medial and lateral walls of the frontal and
      parietal lobes. No regions showed significant group differences in [11C]-L
      deprenyl-D2 signal, including those demonstrating elevated [11C]PBR28 signal in
      patients (p's >= 0.53, uncorrected). The elevations in [11C]PBR28 VT and SUVR
      were correlated both spatially (i.e., were observed in overlapping regions) and,
      in several areas, also in terms of magnitude. In exploratory, uncorrected
      analyses, higher subjective ratings of fatigue in FM patients were associated
      with higher [11C]PBR28 SUVR in the anterior and posterior middle cingulate
      cortices (p's < 0.03). SUVR was not significantly associated with any other
      clinical variable. Our work provides the first in vivo evidence supporting a role
      for glial activation in FM pathophysiology. Given that the elevations in
      [11C]PBR28 signal were not also accompanied by increased [11C]-L-deprenyl-D2
      signal, our data suggests that microglia, but not astrocytes, may be driving the
      TSPO elevation in these regions. Although [11C]-L-deprenyl-D2 signal was not
      found to be increased in FM patients, larger studies are needed to further assess
      the role of possible astrocytic contributions in FM. Overall, our data support
      glial modulation as a potential therapeutic strategy for FM.

PMID- 30223012
TI  - A Regional Experience with Carotid Endarterectomy in Patients with a History of
      Neck Radiation.
AB  - OBJECTIVES: Historically, a history of neck radiation has been consider an
      anatomic risk factor for poor outcomes after carotid endarterectomy (CEA).
      However, this is based on small and primarily single institution reports with few
      comparative series. This study uses a regional quality database to compare
      perioperative outcomes of CEA in patients with and without a history of neck
      radiation (RAD and NORAD, respectively). METHODS: The Vascular Study Group of New
      England (VSGNE) database was queried for all CEA from 2003-2017. The RAD group
      included history of neck radiation. Primary endpoints included perioperative
      stroke (30-day), myocardial infarction (MI) (in-hospital), death (30-day), a
      composite endpoint: major adverse events (MAE: stroke, MI, death) and long-term
      survival. RESULTS: Overall, 18,832 patients underwent CEA (18,551 NORAD, 281
      RAD). Baseline demographics differed in the following: the RAD group more
      frequently had history of contralateral carotid artery stenting (1.4% vs. 0.3%, P
      = 0.009), anatomic high risk features (12.8% vs. 1.3%, P < 0.001) and
      contralateral carotid occlusion (5.3% vs. 2.4%, P = 0.005). The NORAD cohort was
      more frequently female (38.9% vs. 29.5%, P < 0.001), ASA class 4 or 5 (8.0% vs.
      4.6%, P = 0.035), higher body mass index (28.3 +/- 5.6 vs. 27.1 +/- 5.4, P <
      0.001), on a beta blocker preoperatively (68.0% vs. 62.3%, P = 0.042) and had
      major cardiovascular comorbidities including coronary artery disease (29.6% vs.
      22.1%, P = 0.006). There were no differences in the percent stenosis, proportion
      symptomatic (37.4% vs. 34.2%, P = 0.259), use of preoperative antiplatelet agents
      or statins. Electroencephalography monitoring was more frequently employed in RAD
      (54.5% vs. 46.0%, P = 0.005). There was no difference in perioperative
      complications, including stroke (RAD 0.4% vs. NORAD 0.7%, P > 0.999), MI (0.4%
      vs. 0.9%, P = 0.736), death (0.7% vs. 0.6%, P = 0.683) or MAE (2.1% vs. 2.2%, P >
      0.999) or long-term survival (79.9% vs. 85.0%, P = 0.357). When only symptomatic
      or asymptomatic stenosis was considered, there remained no difference in primary
      endpoints. However, perioperative neurologic events (TIA or stroke) was higher in
      symptomatic RAD versus symptomatic NORAD (6.7% vs. 2.6%, P = 0.020). CONCLUSIONS:
      This regional experience with CEA in patients with RAD shows similar
      perioperative morbidity, mortality and long term survival when compared with CEA
      for standard surgical patients (NORAD). Symptomatic presentation was associated
      with higher perioperative neurologic events but this was not reflected in stroke
      rates. RAD is not always a contra-indication to CEA and select patients can
      expect outcomes comparable to standard surgical patients.

PMID- 30223013
TI  - Pain and Emergency Department Use in the Last Month of Life Among Older Adults
      With Dementia.
AB  - CONTEXT: Pain may be a potentially modifiable risk factor for expensive and
      burdensome emergency department (ED) visits near the end of life for older adults
      with dementia. OBJECTIVES: The objective of this study was to assess the effect
      of pain and unmet need for pain management on ED visits in the last month of life
      in older adults with dementia. METHODS: This is a mortality follow-back study of
      older adults with dementia in the National Health and Aging Trends Study who died
      between 2012 and 2014, linked to Medicare claims. RESULTS: Two hundred eighty-one
      National Health and Aging Trends Study decedents with dementia met criteria (mean
      age 86 years, 61% female, 81% white). Fifty-seven percent had at least one ED
      visit in the last month of life, and 46.5% had an ED visit that resulted in a
      hospital admission. Almost three out of four (73%) of decedents experienced pain
      in the last month of life, and 10% had an unmet need for pain management. After
      adjustment for age, gender, race, educational attainment, income, comorbidities,
      and impairment in activities of daily living, pain was not associated with
      increased ED use in the last month of life (adjusted incident rate ratio 0.87,
      95% CI 0.64-1.17). However, decedents with unmet need for pain management had an
      almost 50% higher rate of ED visits in the last month of life than those without
      unmet needs (adjusted incident rate ratio 1.46, 95% CI 1.07-1.99). CONCLUSION:
      Among older adults with dementia, unmet need for pain management was associated
      with more frequent ED visits in the last month of life.

PMID- 30223014
TI  - Fidelity and Feasibility of a Brief Emergency Department Intervention to Empower
      Adults With Serious Illness to Initiate Advance Care Planning Conversations.
AB  - CONTEXT: Emergency department (ED) visits provide opportunities to empower
      patients to discuss advance care planning with their outpatient clinicians, but
      systematically developed, feasible interventions do not currently exist. Brief
      negotiated interview (BNI) interventions, which allow ED clinicians to
      efficiently motivate patients, have potential to meet this need. OBJECTIVES: We
      developed a BNI ED intervention to empower older adults with life-limiting
      illness to formulate and communicate medical care goals to their primary
      outpatient clinicians. This study assessed the fidelity and feasibility of this
      intervention in a high-volume ED. METHODS: We enrolled adult patients with
      serious illnesses (advanced cancer, congestive heart failure, chronic obstructive
      pulmonary disease, chronic kidney disease on dialysis, predicted survival <12
      months) in an urban, tertiary care academic medical center ED. All participants
      received the BNI intervention. We video-recorded the encounters. Two reviewers
      assessed the recordings for intervention fidelity based on adherence to the BNI
      steps (Part I) and communication skills (Part II). RESULTS: We reviewed 46 video
      recordings. The mean total adherence score was 21.07/27 (SD 3.68) or 78.04%. The
      Part I mean adherence score was 12.07/15 (SD 2.07) or 80.47%. The Part II mean
      adherence score was 9.0/12 (SD 2.51) or 75%. The majority (75.6%) of recordings
      met the prespecified threshold for high intervention fidelity. CONCLUSION: ED
      clinicians can deliver a BNI intervention to increase advance care planning
      conversations with high fidelity. Future research is needed to study the
      intervention's efficacy in a wider patient population.

PMID- 30223015
TI  - Walking but Not Talking: Laryngeal Separation as a Novel Approach to Improve
      Quality of Life in Bulbar Amyotrophic Lateral Sclerosis.

PMID- 30223017
TI  - RNF186 impairs insulin sensitivity by inducing ER stress in mouse primary
      hepatocytes.
AB  - RING finger 186 (RNF186) is involved in the process of endoplasmic reticulum (ER)
      stress-mediated apoptosis and inflammation of different cell types, such as HeLa
      cells and colon epithelial cells. However, the physiological and functional roles
      of RNF186 in peripheral tissues remain largely unknown. In the current study, we
      investigate the physiological function of RNF186 in the regulation of ER stress
      with respect to its biological roles in regulating insulin sensitivity in mouse
      primary hepatocytes. RNF186 expression is induced in the livers of diabetic,
      obese and diet-induced obese (DIO) mice. Mouse primary hepatocytes were isolated
      and treated with Ad-RNF186 or Ad-GFP. The results suggest that overexpression of
      RNF186 increases the protein levels of the ER stress sensors inositol requiring
      kinase 1 (IRE1) and C/EBP homologous protein (CHOP) protein, as well as the
      phosphorylation level of eukaryotic initiation factor 2alpha (eIF2alpha), in
      mouse primary hepatocytes. This effect impedes the action of insulin through c
      Jun N-terminal kinase (JNK)-mediated phosphorylation of insulin receptor
      substrate 1 (IRS1). Furthermore, overexpression of RNF186 also significantly
      increases the levels of proinflammatory cytokines, including TNFalpha, IL-6 and
      MCP1. In addition, tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor,
      alleviates the expression of ER stress markers induced by RNF186 overexpression.
      Taken together, the results of the present study show that overexpression of
      RNF186 induces ER stress and impairs insulin signalling in mouse primary
      hepatocytes, suggesting that RNF186 merits further investigation as a potential
      therapeutic target for treatment of insulin-resistance-associated metabolic
      diseases.

PMID- 30223016
TI  - Cyclin-dependent kinase 1-mediated phosphorylation of YES links mitotic arrest
      and apoptosis during antitubulin chemotherapy.
AB  - YES is a member of the SRC family kinase (SFK) group of non-receptor tyrosine
      kinases, which are implicated in multiple key cellular processes involved in
      oncogenesis. Antitubulin agents have been widely used as chemotherapeutics for
      cancer patients and these drugs arrest cells in mitosis, leading to subsequent
      cell death. In the present study, we define a mechanism for phospho-regulation of
      YES that is critical for its role in response to antitubulin agents.
      Specifically, we found that YES is phosphorylated at multiple sites on its N
      terminal unique domain by the cell cycle kinase CDK1 during antitubulin drug
      induced mitotic arrest. Phosphorylation of YES occurs during normal mitosis.
      Deletion of YES causes arrest in prometaphase and polyploidy in a p53-independent
      manner. We further show that YES regulates antitubulin chemosensitivity.
      Importantly, mitotic phosphorylation is essential for these effects. In support
      of our findings, we found that YES expression is high in recurrent ovarian cancer
      patients. Finally, through expression profiling, we documented that YES
      phosphorylation affects expression of multiple cell cycle regulators.
      Collectively, our results reveal a previously unrecognized mechanism for
      controlling the activity of YES during antitubulin chemotherapeutic treatment and
      suggest YES as a potential target for the treatment of antitubulin-resistant
      cancer.

PMID- 30223018
TI  - Lack of superoxide dismutase in a rad51 mutant exacerbates genomic instability
      and oxidative stress-mediated cytotoxicity in Saccharomyces cerevisiae.
AB  - A genetic analysis of synthetic lethal interactions in yeast revealed that the
      mutation of SOD1, encoding an antioxidant enzyme that scavenges superoxide anion
      radical, impaired the growth of a set of mutants defective in homologous
      recombination (HR) pathway. Hence, SOD1 inhibition has been proposed as a
      promising approach for the selective killing of HR-deficient cancer cells.
      However, we show that the deletion of RAD51 and SOD1 is not synthetic lethal but
      displays considerably slow growth and synergistic sensitivity to both reactive
      oxygen species (ROS)- and DNA double-strand break (DSB)-generating drugs in the
      budding yeast Saccharomyces cerevisiae. The function of Sod1 in regard to Rad51
      is dependent on Ccs1, a copper chaperone for Sod1. Sod1 deficiency aggravates
      genomic instability in conjunction with the absence of Rad51 by inducing DSBs and
      an elevated mutation frequency. Inversely, lack of Rad51 causes a Sod1 deficiency
      derived increase of intracellular ROS levels. Taken together, our results
      indicate that there is a significant and specific crosstalk between two major
      cellular damage response pathways, ROS signaling and DSB repair, for cell
      survival.

PMID- 30223019
TI  - VAOS, a novel vanadyl complexes of alginate saccharides, inducing apoptosis via
      activation of AKT-dependent ROS production in NSCLC.
AB  - Previous studies have confirmed that protein tyrosine phosphatase 1B (PTP1B) can
      promote tumour progression in non-small cell lung cancer (NSCLC). Vanadyl
      alginate oligosaccharides (VAOS) is a new coordination compounds that possesses a
      good PTP1B inhibitory activity. However, the potent anticancer efficacy of VAOS
      in human NSCLC requires further study. In this study, VAOS exhibited effective
      inhibitory effects in NSCLC both in cultured cells and in a xenograft mouse
      model. VAOS was further identified to induce NSCLC cell apoptosis through
      activating protein kinase B (AKT) to elevate intracellular reactive oxygen
      species (ROS) levels by increasing in oxygen consumption and impairing the ROS
      scavenging system. Neither silencing of PTP1B by siRNA nor transient
      overexpression of PTP1B had an effect on the AKT phosphorylation triggered by
      VAOS, indicating that PTP1B inhibition was not involved in VAOS-induced
      apoptosis. Through phosphorus colorimetric assay, we demonstrated that VAOS
      notably inhibited phosphatase and tensin homologue deleted on chromosome 10
      (PTEN) dephosphorylation activity, another member of the protein tyrosine
      phosphatases (PTPases)-upstream factor of AKT. Interestingly, PTEN knockdown
      sensitized cells to VAOS, whereas ectopic expression of PTEN markedly rescued
      VAOS-mediated lethality. In vivo, VAOS treatment markedly reduced PTEN activity
      and tumour cell burden with low systemic toxicity. Thus, our data not only
      provided a new therapeutic drug candidate for NSCLC, but presented new
      understanding into the pharmacological research of VAOS.

PMID- 30223021
TI  - The Short-Term Effect of Slope Walking on Soleus H-Reflexes in People with
      Multiple Sclerosis.
AB  - Downslope walking (DSW) causes H-reflex depression in healthy adults, and thus
      may hold promise for inducing spinal reflex plasticity in people with Multiple
      Sclerosis (PwMS). The study purpose was to test the hypothesis that DSW will
      cause acute depression of spinal excitability in PwMS. Soleus H-reflexes were
      measured in PwMS (n = 18) before and after 20 min of treadmill walking during
      three visits. Participants walked on a different slope each visit [level: 0%
      level walking (LW), upslope: +7.5% treadmill walking with an upslope (USW) or
      downslope: -7.5% (DSW)]. The soleus Hmax/Mmax ratio was used to measure spinal
      excitability. Heart rate and ratings of perceived exertion (RPE) were measured
      during walking. DSW induced the largest change in spinal excitability (a 26.7%
      reduction in soleus Hmax/Mmax (p = 0.001)), although LW also reduced Hmax/Mmax (
      5.3%, p = 0.05). Heart rate (p < 0.001) was lowest for DSW, and RPE for DSW did
      not exceed "Fairly light". DSW evokes short-term spinal plasticity in PwMS, while
      requiring no greater effort than LW. Our results suggest that PwMS retain the
      capacity for DSW-induced short-term spinal reflex modulation previously found in
      healthy adults. These results may provide a foundation for further investigation
      of long-term effects of DSW on spinal reflex plasticity and functional ability in
      PwMS.

PMID- 30223022
TI  - CRISPR-Cas9 targeting of MMP13 in human chondrocytes leads to significantly
      reduced levels of the metalloproteinase and enhanced type II collagen
      accumulation.
AB  - OBJECTIVE: To investigate the efficacy of CRISPR-Cas9 mediated editing in human
      chondrocytes, and to develop a genome editing approach relevant to cell-based
      repair. METHODS: Transfection of human articular chondrocytes (both healthy and
      osteoarthritic) with ribonucleoprotein complexes (RNP) containing Cas9 and a
      crisprRNA targeting exon2 of MMP13 was performed to assess editing efficiency and
      effects on MMP13 protein levels and enzymatic activity. Using spheroid cultures,
      protein levels of a major target of MMP13, type II collagen, were assessed by
      western blot and immunofluorescence. RESULTS: With an editing efficiency of 63
      74%, secreted MMP13 protein levels and activity were significantly reduced
      (percentage decrease 34.14% without and 67.97% with IL-1beta based on median
      values of MMP13 enzymatic activity, N = 7) comparing non-edited with edited cell
      populations using an exon-targeting gRNA resulting in premature stop codons
      through non-homologous end joining (NHEJ). Accumulation of cartilage matrix
      protein type II collagen was enhanced in edited cells in spheroid culture,
      compared to non-edited controls. CONCLUSION: CRISPR-Cas9 mediated genome editing
      can be used to efficiently and reproducibly establish populations of human
      chondrocytes with stably reduced expression of key genes of interest without the
      need for clonal selection. Such an editing approach has the potential to greatly
      enhance current cell-based therapies for cartilage repair.

PMID- 30223020
TI  - 2-(4-Methoxyphenyl)ethyl-2-Acetamido-2-deoxy-beta-d-pyranoside (A Salidroside
      Analog) Confers Neuroprotection with a Wide Therapeutic Window by Regulating
      Local Glucose Metabolism in a Rat Model of Cerebral Ischemic Injury.
AB  - 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-beta-d-pyranoside (salidroside
      analog-4g, SalA-4g), has shown neuroprotective prospects for the treatment of
      ischemic stroke. However, the dose-response and time window study for SalA-4g,
      and the mechanism of SalA-4g-mediated neuroprotection remain unclear. Here, we
      systematically investigated the therapeutic time window and dosage of SalA-4g in
      permanent focal cerebral ischemia in rats. SalA-4g dose-dependently improved
      stroke outcome. Either pre-treatment or post-treatment of SalA-4g exhibited
      notable neuroprotection, and maintained for up to 6 h after ischemia onset.
      Moreover, significant neurological functional recovery was found after SalA-4g
      administration in long-term functional assays. Further studies suggested that
      SalA-4g ameliorated neuronal cell death, elevated local glucose metabolism and
      enhanced the expression level of glucose transporter 1 and 3 in the ipsilateral
      cortex and striatum. We suggest that data of this study are critical in exploring
      the clinical application prospects of SalA-4g for the treatment of ischemic
      stroke.

PMID- 30223023
TI  - Evaluating the use of intra-articular injections as a treatment for painful hip
      osteoarthritis: a randomized, double-blind, multicenter, parallel-group study
      comparing a single 6-mL injection of hylan G-F 20 with saline.
AB  - OBJECTIVE: Hip osteoarthritis (OA) is difficult to treat. Steroid injections
      reduce pain with short duration. With widespread adoption of office-based, image
      guided injections, hyaluronic acid is a potentially relevant therapy. In the
      largest clinical trial to-date, we compared safety/efficacy of a single, 6-mL
      image-guided injection of hylan G-F 20 to saline in painful hip OA. METHOD: 357
      patients were enrolled in a multicenter, double-blind, randomized saline placebo-
      controlled trial. Subjects were >=35 years of age, with painful (Western Ontario
      and McMaster Universities Osteoarthritis Index [WOMAC]-A1:5.0-8.0; numeric rating
      scale [NRS]: 0-10) mild-to-moderate hip OA (Kellgren-Lawrence grade II/III) and
      minimal contralateral hip pain (WOMAC-A1 < 4). Outcome measures included "pain on
      walking" (WOMAC-A1 and -A), Patient Global Self-Assessment (PTGA), WOMAC-A1
      responder rate (+>=2 points on NRS), and adverse events (AEs) over 26 weeks.
      RESULTS: 357 patients (hylan G-F 20 single:182; saline:175) were enrolled. Both
      groups demonstrated significant pain improvement from baseline over 26 weeks (P <
      0.0001); saline-induced pain reduction was a remarkable 35%. WOMAC-A and PTGA
      scores also significantly improved (P < 0.0001). No statistically significant
      difference was observed between groups in WOMAC-A1 scores (hylan G-F 20 single:
      2.19 +/- 0.16; saline:-2.26 +/- 0.17) or WOMAC-A1 responders (41-52%). Treatment
      related AE rates at target hip were similar (hylan G-F 20 single:23 patients
      [12.8%]; saline:12 [7.0%]). Posthoc analysis found, despite protocol
      requirements, many patients had psychological (31%) or potential neuropathic pain
      (27.5%) conditions. CONCLUSION: A single 6-mL hylan G-F 20 injection or saline
      for painful hip OA resulted in similar, statistically significant/clinically
      relevant pain and function improvements up to 6 months following injection; no
      differences between hylan G-F 20 and saline placebo were observed.

PMID- 30223024
TI  - Pelvic Castleman's Disease Presenting as an Adnexal Mass in an Adolescent.
AB  - BACKGROUND: Castleman disease (CD) is a rare lymphoproliferative disorder that
      might present as an adnexal mass. We report a case of pelvic CD in an adolescent
      girl who presented with abdominal pain. CASE: A 13-year-old girl presented with
      severe abdominal pain, nausea, and vomiting, and was found to have a solid
      adnexal mass. Repeat imaging revealed the mass to be retroperitoneal and in the
      left pelvic side wall. She underwent surgical removal via an open retroperitoneal
      approach, and pathology revealed CD, hyaline vascular variant subtype. SUMMARY
      AND CONCLUSION: Pelvic CD should be considered in the differential diagnosis for
      an adnexal mass in a young woman. Surgical planning is critical because of the
      possibility of extension and mass effect. Most pelvic CD is unicentric, hyaline
      vascular variant subtype, and does not recur after surgical removal.

PMID- 30223025
TI  - Patterns and Correlates of Self-Reported Physical Activity in a Cohort of
      Racially Diverse Pregnant Adolescents.
AB  - STUDY OBJECTIVE: Regular physical activity (PA) during pregnancy decreases the
      risk of gestational hypertension and preeclampsia. Currently, little is known
      about the PA of pregnant adolescents. Our intent was to characterize the PA
      behaviors of a group of racially diverse, low-income pregnant teens and to
      identify potential determinants of PA. DESIGN, SETTING, PARTICIPANTS, AND
      INTERVENTIONS: A cohort of 157 racially diverse pregnant adolescents (13-18 years
      of age) completed up to 3 previous day PA recalls as part of a larger prospective
      longitudinal study on determinants of maternal and fetal bone health. Subjects
      self-reported activities from 7 AM to 11:30 PM, choosing from a list of 37
      activities including a category for "other." Subjects recorded activities in 30
      minute intervals. MAIN OUTCOME MEASURES: Estimated metabolic equivalent task
      (MET) values were assigned to each activity and summed for a measure of total
      daily PA in MET min/d. Determinants of PA were evaluated using a stepwise linear
      mixed effect model. RESULTS: The average calculated MET min/d was 1478 +/- 130.
      Significant determinants of MET min/d included race (P = .007), maternal age at
      conception (P = .042), gestational age (P = .002), and attending school (P <
      .001). Black teens were less physically active than white teens, and older teens
      were more active than younger teens; activity decreased throughout gestation, and
      teens currently attending school were more active. CONCLUSION: PA is low across
      gestation and pregnant teens spent more than half of their monitored time in
      sedentary activities. Targeted interventions are needed to achieve current PA
      goals in this pediatric obstetric population.

PMID- 30223026
TI  - High production of 4-hydroxyisoleucine in Corynebacterium glutamicum by multistep
      metabolic engineering.
AB  - 4-Hydroxyisoleucine (4-HIL) exhibits a unique glucose-dependent insulinotropic
      activity and is a promising candidate for the treatment of diabetes. Direct
      fermentation of 4-HIL has been recently studied; however, the expected titre and
      yield were not achieved. In this study, we initially developed a pathway for the
      synthesis of 4-HIL in an L-isoleucine producer, C. glutamicum YI, but
      insufficient supply of alpha-ketoglutarate was a bottleneck for a strong
      production. Six genes involved in oxaloacetate and alpha-ketoglutarate branches
      were overexpressed or deleted, which increased the production of 4-HIL to 5.12
      g/L but a considerable amount of L-isoleucine still accumulated in the culture.
      We then dynamically modulated the activity of the alpha-ketoglutarate
      dehydrogenase complex (ODHC) by employing L-isoleucine-responsive transcription
      or attenuation strategies. The best-engineered strain, HIL18, produced 34.21 g/L
      4-HIL with a negligible accumulation of byproducts, including approximately 0.6
      g/L L-isoleucine. This study achieved the highest production and yield of 4-HIL,
      and optimizing the TCA cycle by dynamically modulating the activity of ODHA can
      be a powerful strategy to balance the carbon flux and achieve efficient
      production of alpha-ketoglutarate and derivatives.

PMID- 30223027
TI  - 'A pragmatic approach for mortality prediction after surgery in infective
      endocarditis' - Author's reply.

PMID- 30223028
TI  - Thermosensitive liposomes for triggered release of cytotoxic proteins.
AB  - Lysolipid-containing thermosensitive liposomes (LTSL) are clinically-relevant
      drug nanocarriers which have been used to deliver small molecule cytostatics to
      tumors in combination with local hyperthermia (42  degrees C) to trigger local
      drug release. The objective of this study was to investigate the feasibility of
      LTSL for encapsulation and triggered release of macromolecular drugs such as
      plant-derived cytotoxins. As therapeutic protein we used Mistletoe lectin-1 (ML1)
      - a ribosome-inactivating protein with potent cytotoxic activity in tumor cells.
      Model macromolecules (dextrans, albumin) and ML1 were encapsulated in small
      unilamellar LTSL with varying lipid compositions by the thin film hydration
      method and extrusion. LTSLs showed molecular weight dependent heat-triggered
      release of the loaded cargo. The most promising composition, ML1 formulated in
      LTSL composed of 86:10:4 %mol DPPC:MSPC:DSPE-PEG2000, was further studied for
      bioactivity against murine CT26 colon carcinoma cells. Confocal live-cell imaging
      showed uptake of released ML1 after mild hyperthermia at 42  degrees C,
      subsequently leading to potent cytotoxicity by LTSL-ML1. Our study shows that
      LTSL in combination with localized hyperthermia hold promise as local tumor
      delivery strategy for macromolecular cytotoxins.

PMID- 30223029
TI  - S-Nitrosoglutathione loaded poly(lactic-co-glycolic acid) microparticles for
      prolonged nitric oxide release and enhanced healing of methicillin-resistant
      Staphylococcus aureus-infected wounds.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds have become a
      significant clinical issue worldwide. Recently, nitric oxide (NO) has emerged as
      a potent antibacterial agent against MRSA infections and a wound-healing
      enhancer. Nevertheless, clinical applications of NO have been largely restricted
      by its gaseous state and short half-life. In this study, our aim was to develop S
      nitrosoglutathione (GSNO, an endogenous NO donor)-loaded poly(lactic-co-glycolic
      acid) [PLGA] microparticles (GSNO-MPs) that release NO over a prolonged period,
      to accelerate the healing of MRSA-infected wounds with less frequent dosing. GSNO
      was successfully encapsulated into PLGA microparticles by a solid-in-oil-in-water
      emulsion solvent evaporation method. Scanning electron microscopy and X-ray
      diffraction analyses confirmed the successful fabrication of GSNO-MPs. The latter
      released NO in a prolonged manner over 7 days and exerted a remarkable
      antibacterial activity against MRSA in a concentration- and time-dependent
      manner. Moreover, GSNO-MPs had good antibacterial efficacy and were found to
      accelerate wound healing in a mouse model of MRSA-infected wounds. Therefore, NO
      releasing MPs devised in this study may be a promising option for the treatment
      of cutaneous wounds infected by drug-resistant bacteria such as MRSA.

PMID- 30223030
TI  - Estimation of Incident Heart Failure Risk among US Hispanics/Latinos Using a
      Validated Echocardiographic Risk-Stratification Index: the Echocardiographic
      Study of Latinos.

PMID- 30223031
TI  - Will the Early Use of Biomarkers Prevent the Development of Heart Failure?
AB  - Alterations in biomarkers are associated with the development and progression of
      heart failure. As indicated by the study of Ergatoudes and colleagues in the
      current issue of this journal, biomarkers may also be the first sign of increased
      risk of developing heart failure. Prior studies also suggest that elevations in
      certain biomarkers can lead to more frequent clinical surveillance and initiation
      of therapeutic strategies that may prevent or delay the development of heart
      failure.

PMID- 30223032
TI  - Mucosal immune parameters, immune and antioxidant defence related genes
      expression and growth performance of zebrafish (Danio rerio) fed on Gracilaria
      gracilis powder.
AB  - In the present study zebrafish (Danio rerio) has been used as model organism to
      establish the effects of dietary supplementation of Gracilaria gracilis powder
      (GP) on mucosal and innate immune parameters, antioxidant enzymes, and growth. In
      order to establish these features, zebrafish were fed for eight weeks with
      experimental diets containing different levels of Red algae, 0.25, 0.5 and 1% of
      GP; also, a group was fed with control diet. At the end of the experimental
      period the antioxidant superoxide dismutase and catalase (SOD, CAT) genes
      expression, interleukin 1 beta (il-1beta), ?lysozyme (LYZ), tumor necrosis factor
      alpha (TNF-alpha) for immune-related genes expression, total immunoglobulin (Ig),
      total protein, ?alkaline phosphatase (ALP) activity for innate immune parameters,
      and growth performance have been established. The GP dietary supplementation
      showed differences in SOD and CAT expression in zebrafish whole body respect to
      the control group. Non-signifcant differences were noticed among the different
      groups in case of TNF-alpha, LYZ and il-1expression (P > 0.05). The skin mucus
      total Ig and total protein in the group fed on 1% of GP were significantly higher
      respect to control group (P < 0.05). 0.25 and 0.5% of GP dietary supplementation
      significantly enhanced skin mucus ALP activity levels (P < 0.05). No significant
      differences were recorded for growth performances among groups (P > 0.05). The
      results obtained in the present study revealed that G. gracilis could be takes in
      account as fishes diet supplementation for its immune system stimulants effects.

PMID- 30223033
TI  - Bacterial efflux transporters in the limelight.

PMID- 30223035
TI  - Modelling the in-vitro dissolution and release of sumatriptan succinate from
      polyvinylpyrrolidone-based microneedles.
AB  - A mathematical model was developed to predict the transport of sumatriptan
      molecules across the skin followed by absorption into the bloodstream. The drug
      was encapsulated in dissolving polyvinylpyrrolidone-based microneedles shaped in
      the form of pyramids. Mass balance equations were derived to simulate the
      dissolution and transport of the pharmaceutical ingredient. The theoretical
      framework made it possible to assess and predict the effects of key parameters on
      the release profile. The skin concentration increased with the loading dose and
      the height of the microneedle. An inverse relationship was noted between the
      amount of drug released in the dermal layer and the pitch width. These results
      were validated with in-vitro diffusion studies previously conducted using
      Gottingen minipig skin. The new mathematical approach successfully explained the
      in-vitro permeation of three different sumatriptan-containing formulations.

PMID- 30223034
TI  - Porphyrins to restrict progression of pancreatic cancer by stabilizing KRAS G
      quadruplex: In silico, in vitro and in vivo validation of anticancer strategy.
AB  - KRAS, a frequently mutated G-quadruplex forming proto-oncogene is responsible for
      almost every type of cancer which can form a parallel G-quadruplex structure in
      the promoter region. G-quadruplex structure is one of the most important drug
      targets for modern cancer therapy for their unique structure and specificity.
      Here, we have screened several synthetic porphyrin-based compounds as potential
      KRAS G-quadruplex stabilizing ligands, using molecular modeling and docking
      studies. Two novel porphyrins: Porphyrin-1(Cobalt containing) and Porphyrin-2
      (Palladium containing) evidenced high affinity towards KRAS-promoter/G
      quadruplex. As KRAS mutation is prevalent in pancreatic cancer, the efficacy of
      these ligands against human pancreatic ductal carcinoma cell line PANC-1 and
      MiaPaCa2 were examined. Both the Porphyrins exhibited significant cytotoxicity
      and block metastasis by inhibiting Epithelial to messenchymal transition. In vivo
      studies confirmed both porphyrin compounds to be effective against EAC tumors
      along with significantly low toxicity against normal Swiss albino mice. The
      expression of KRAS gene in porphyrin-treated PANC-1, MiaPaCa2 and tumor-derived
      EAC cells were drastically reduced at both protein and RNA levels. Thus
      interaction of porphyrin-based ligands with G-quadruplex DNA at the promoter
      region of KRAS, might be utilized as a target for anticancer therapeutic
      strategy.

PMID- 30223036
TI  - The thoracic morphology of cave-dwelling and free-living ground beetles from
      China (Coleoptera, Carabidae, Trechinae).
AB  - External and internal thoracic structures of two carabid species (Trechini) were
      examined and documented with different techniques. The study has a main focus on
      the eyeless cave-dwelling specialist Sinaphaenops wangorum, but detailed
      information is also provided for a species occurring in cave entrances. The
      phylogenetic background of the structural features of the thoracic
      skeletomuscular system was addressed. The thoracic morphology of the examined
      species was compared to conditions observed in previously studied carabids and
      non-related subterranean leiodids (Staphylinoidea) in order to identify cave
      adaptations. Main thoracic character complexes linked with cavernicolous habits
      in Trechini are elongation of the pro- and mesothorax and the legs, and a
      complete and irreversible reduction of the flight apparatus. The lost flight
      capacity is linked with a far reaching modification of skeletal elements of the
      metathorax including a strongly shortened and simplified metanotum, a shortened
      metaventrite, and completely reduced wings and sclerites of the wing base. The
      elongate prothorax together with the long and slender head and elongated legs
      distinctly increases the activity range in the subterranean lightless
      environment, which likely facilitates foraging of the carnivorous beetles. Some
      of the observed features like wing loss and elongation of the anterior thorax and
      legs are also found in some cave-dwelling Leiodidae (Leptodirini), whereas some
      other subterranean members of the staphylinoid family have a compact body and
      legs of normal length. In contrast to the predaceous Trechini, Leptodirini are
      scavengers.

PMID- 30223037
TI  - Omega-3 PUFA attenuate mice myocardial infarction injury by emerging a protective
      eicosanoid pattern.
AB  - Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation is a recommended
      preventive approach against cardiovascular diseases, but its mechanism of
      protection against myocardial infarction (MI) injury is not fully understood.
      Eicosanoid metabolomics demonstrated an abnormal eicosanoid profile was in the
      plasma of mice receiving MI surgery. 19,20-EDP, 17,18-EEQ, 14,15-EET and 9,10
      EpOME were decreased, and PGE2 was increased by the surgery. N-3 PUFA-rich diets
      feeding or transgene of Fat-1 shifted the eicosanoid profile to an n-3 PUFA
      dominant style and attenuated the myocardial infarction injury. Multiple logistic
      regression analysis suggested the degree of MI injury was related with an
      eicosanoid pattern, composed by eicosanoids derived from both n-3 and n-6 PUFA in
      the three enzymatic pathways. These results suggested the benefits of n-3 PUFA on
      MI was achieved synergistically.

PMID- 30223038
TI  - Ictal Asystole Induced by Right Posterior Quadrant Epilepsy: Report of a
      Radically Treated Case.
AB  - BACKGROUND: Ictal asystole (IA) and ictal bradycardia (IB) are mainly seen with
      temporal or frontal lobe epilepsy. Many patients with these conditions undergo
      cardiac pacemaker therapy but not epilepsy surgery. CASE DESCRIPTION: We report
      the case of a 15-year-old boy with IA and IB secondary to right posterior
      quadrant epilepsy (PoQE) who underwent right posterior quadrant disconnection,
      but not cardiac pacemaker implantation. He has remained free from daily epileptic
      seizures, IA, and IB for more than 6 months postoperatively. This is the first
      report of a radically treated case with IA and IB caused by PoQE. CONCLUSIONS:
      Both temporofrontal lobe epilepsy and PoQE caused the IA and IB. Because a
      cardiac pacemaker only addresses arrhythmia, not epileptic seizures, radical
      treatment for both epilepsy and arrhythmia may be warranted for patients with
      medically intractable epilepsy.

PMID- 30223039
TI  - Lost medicines: a longer view of the pharmaceutical industry with the potential
      to reinvigorate discovery.
AB  - It is widely understood that the 1962 Kefauver-Harris Amendment to the Food, Drug
      and Cosmetics Act ushered in the modern regulation of medicines requiring a
      combination of safety and efficacy. However, fewer appreciate the amendment was
      applied retroactively to virtually all medicines sold in the USA. For various
      reasons, many medicines faded into history. Here, we identify and analyze >1600
      medicines (including over-the-counter drugs) and their innovators prior to the
      enactment of Kefauver-Harris. We report 880 of these past medicines are no longer
      accessible. This project also reveals new insight into the pharmaceutical
      enterprise, which reveals an industry already mature and beginning to retract
      before enactment of the legislation. Beyond its historical implications, the
      recollection of these medicines could offer potential starting points for the
      future development of much-needed drugs.

PMID- 30223040
TI  - Characterization of a novel antioxidant peptide from feather keratin
      hydrolysates.
AB  - Feather hydrolysates were obtained through submerged cultivation of 50 g/L
      feathers with Chryseobacterium sp. kr6. Culture supernatants, displaying
      antioxidant properties, as evaluated by the 2,2'-azino-bis-(3
      ethylbenzothiazoline)-6-sulfonic acid (ABTS) radical scavenging method, were
      partially purified by gel-filtration chromatography. Fractions showing scavenging
      activity were pooled, lyophilized and tested at different concentrations (0.1-1.0
      mg/mL) by the total reactive antioxidant potential (TRAP) method, showing
      promising antioxidant capacities. Antioxidant activities of the partially
      purified feather hydrolysate (PPFH; 24.5 MUg) were demonstrated by its ability to
      scavenge hydroxyl radicals and to inhibit lipid peroxidation. In addition, PPFH
      (0.24-24.5 MUg) was found to reduce ferric ion (Fe3+), but did not display Fe2+
      chelating activity. Thus, the main antioxidant activities could be related to the
      donation of hydrogen atoms, electron transfer and scavenging of hydroxyl
      radicals. PPFH was analyzed by mass spectrometry and five peptides were
      identified and chemically synthesized. The antioxidant activity of one peptide
      LPGPILSSFPQ was confirmed by ABTS and TRAP. The structure of this keratin-derived
      bioactive peptide has not been previously described.

PMID- 30223041
TI  - Attractive but Toxic: Emerging Roles of Glycosidically Bound Volatiles and
      Glycosyltransferases Involved in Their Formation.
AB  - Plants emit an overabundance of volatile compounds, which act in their producers
      either as appreciated attractants to lure beneficial animals or as repellent
      toxins to deter pests in a species-specific and concentration-dependent manner.
      Plants have evolved solutions to provide sufficient volatiles without poisoning
      themselves. Uridine-diphosphate sugar-dependent glycosyltransferases (UGTs)
      acting on volatiles is one important part of this sophisticated system, which
      balances the levels of bioactive metabolites and prepares them for cellular and
      long-distance transport and storage but enables the remobilization of disarmed
      toxins for the benefit of plant protection. This review provides an overview of
      the research history of glycosidically bound volatiles (GBVs), a relatively new
      group of plant secondary metabolites, and discusses the role of UGTs in the
      production of GBVs for plant protection.

PMID- 30223042
TI  - TSNAdb: A Database for Tumor-specific Neoantigens from Immunogenomics Data
      Analysis.
AB  - Tumor-specific neoantigens have attracted much attention since they can be used
      as biomarkers to predict therapeutic effects of immune checkpoint blockade
      therapy and as potential targets for cancer immunotherapy. In this study, we
      developed a comprehensive tumor-specific neoantigen database (TSNAdb v1.0), based
      on pan-cancer immunogenomic analyses of somatic mutation data and human leukocyte
      antigen (HLA) allele information for 16 tumor types with 7748 tumor samples from
      The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA). We predicted
      binding affinities between mutant/wild-type peptides and HLA class I molecules by
      NetMHCpan v2.8/v4.0, and presented detailed information of 3,707,562/1,146,961
      potential neoantigens generated by somatic mutations of all tumor samples.
      Moreover, we employed recurrent mutations in combination with highly frequent HLA
      alleles to predict potential shared neoantigens across tumor patients, which
      would facilitate the discovery of putative targets for neoantigen-based cancer
      immunotherapy. TSNAdb is freely available at http://biopharm.zju.edu.cn/tsnadb.

PMID- 30223043
TI  - Recent advances in applying nanotechnologies for cancer immunotherapy.
AB  - Cancer immunotherapy aimed at boosting cancer-specific immunoresponses to
      eradicate tumor cells has evolved as a new treatment modality. Nanoparticles
      incorporating antigens and immunomodulatory agents can activate immune cells and
      modulate the tumor microenvironment to enhance anti-tumor immunity. The
      nanotechnology approach has been demonstrated to be superior to standard
      formulations in in-vivo settings. In this article, we focus on recent advances
      made within the last 5 years in nanoparticle-based cancer immunotherapy,
      including peptide- and nucleic acid-based nanovaccines, nanomedicines containing
      an immunoadjuvant to activate anti-tumor immunity, nanoparticle delivery of
      immune checkpoint inhibitors and the combination of the above approaches.
      Encouraging results and new emerging nanotechnologies in drug delivery promise
      the continuous growth of this field and ultimately clinical translation of
      enhanced immunotherapy of cancer.

PMID- 30223044
TI  - Immunoengineering through cancer vaccines - A personalized and multi-step vaccine
      approach towards precise cancer immunity.
AB  - During the last decade anti-tumor immune-therapy has opened novel opportunities
      to efficiently combat cancer progression. The introduction of DC- and CAR T-cell
      based therapies as well as the successful application of antibody-based inhibitor
      of immune checkpoints (CTLA-4, PD1 and PDL1) have boosted the field and led to an
      overall benefit for many patients. In situ cancer vaccination is an attractive
      strategy to further improve the therapeutic outcome, especially towards a more
      personalized and individually tailored immune response against the patient's
      mutanome. Nanoparticle-based delivery platforms can assist in combination
      treatments e.g. with multiple immune stimulatory signales (PAMPs and DAMPs) to
      increase the probability of evoking broader and all-embracing cytotoxic and
      memory T-cell responses. In this review, various approaches and hurdles of cancer
      vaccination are discussed including the beneficial contributions of the thriving
      field of nanoparticle design and functionalization, which may further boost the
      development of cancer immunotherapeutics.

PMID- 30223046
TI  - Improvements in cognition and associations with measures of aerobic fitness and
      muscular power following structured exercise.
AB  - OBJECTIVES: Cognition, along with aerobic and muscular fitness, declines with
      age. Although research has shown that resistance and aerobic exercise may improve
      cognition, no consensus exists supporting the use of one approach over the other.
      The purpose of this study was to compare the effects of steady-state, moderate
      intensity treadmill training (TM) and high-velocity circuit resistance training
      (HVCRT) on cognition, and to examine its relationships to aerobic fitness and
      neuromuscular power. METHODS: Thirty older adults were randomly assigned to one
      of three groups: HVCRT, TM, or control. Exercise groups attended training 3
      days/wk for 12 weeks, following a 2 week adaptation period. The NIH Cognitive
      Toolbox was used to assess specific components of cognition and provided an
      overall fluid composite score (FCS). The walking response and inhibition test
      (WRIT) was specifically used to assess executive function (EF) and provided an
      accuracy (ACC), reaction time (RT) and global score (GS). Aerobic power (AP) and
      maximal neuromuscular power (MP) were measured pre- and post-intervention.
      Relationships between variables using baseline and mean change scores were
      assessed. RESULTS: Significant increases were seen from baseline in ACC (MD =
      14.0, SE = 4.3, p = .01, d = 1.49), GS (MD = 25.6, SE = 8.0, p = .01, d = 1.16),
      and AP (MD = 1.4, SE = 0.6, p = .046, d = 0.31) for HVCRT. RT showed a trend
      toward a significant decrease (MD = -0.03, SE = 0.016, p = .068, d = 0.32) for
      HVCRT. No significant within-group differences were detected for TM or CONT.
      Significant correlations were seen at baseline between AP and FCS, as well as
      other cognitive domains; but none were detected among change scores. Although no
      significant correlation was evident between MP and FCS or GS, there was a trend
      toward higher MP values being associated with higher FCS and GS scores.
      CONCLUSIONS: Our results support the use of HVCRT over TM for improving cognition
      in older persons, although the precise mechanisms that underlie this association
      remain unclear.

PMID- 30223047
TI  - Torquetenovirus (TTV) load is associated with mortality in Italian elderly
      subjects.
AB  - An age-related dysregulation of immune response, known as immunosenescence,
      contributes to increased susceptibility to infections, frailty and high risk of
      mortality in the elderly. Torquetenovirus (TTV), a circular, single-stranded DNA
      virus, is highly prevalent in the general population and it may persist in the
      organism, also in association with other viruses such as cytomegalovirus (CMV),
      causing chronic viremia. The relationship that TTV establishes with the immune
      system of infected hosts is not clear. It is known that TTV encodes microRNAs
      (miRNAs) that might contribute to immune evasion and that the highest viral loads
      are found in peripheral blood cells. Moreover, it is suspected that TTV infection
      lead to increased production of inflammatory mediators, thus playing a role in
      immunosenescence. We investigated the association of TTV load and miRNAs
      expression with inflammatory and immune markers and the influence of TTV load on
      mortality within a cohort of 379 elderly subjects who were followed up for 3
      years. TTV DNA load in polymorphonuclear leukocytes was slightly positively
      correlated with age and negatively associated with serum albumin levels and NK
      cell activity. A marginal positive correlation between TTV DNA load, monocytes
      and IL-8 plasma levels was found in females and males respectively. TTV DNA
      copies >=4.0 log represented a strong predictor of mortality (Hazard ratio =
      4.78, 95% CI: 1.70-13.44, after adjusting for age, sex and the main predictors of
      mortality rate) and this association remained significant even after the CMV IgG
      antibody titer was included in the model (HR = 9.83; 95% CI: 2.48-38.97; N = 343
      subjects). Moreover, multiple linear regression model showed that TTV miRNA-t3b
      of genogroup 3 was inversely associated with triglycerides, monocytes and C
      reactive protein, and directly associated with IL6. Overall these findings
      suggest a role of TTV in immunesenescence and in the prediction of all-cause
      mortality risk in Italian elderly subjects. Further studies are needed to fully
      understand the pathogenic mechanisms of TTV infection during aging.

PMID- 30223045
TI  - Novel glucosylceramide synthase inhibitor based prodrug copolymer micelles for
      delivery of anticancer agents.
AB  - In order to improve the efficacy of chemotherapy for cancers, we have developed a
      novel prodrug micellar formulation to co-deliver ceramide-generating anticancer
      agents and ceramide degradation inhibitor (PPMP). The prodrug nanocarrier is
      based on a well-defined POEG-b-PPPMP diblock copolymer. The hydrophilic block of
      POEG-b-PPPMP is POEG, and the hydrophobic block is composed of a number of PPMP
      units, which could work synergistically with loaded anticancer drugs. POEG-b
      PPPMP was readily synthesized via a one-step reversible addition-fragment
      transfer (RAFT) polymerization from a PPMP monomer. The newly synthesized
      polymers were self-assembled into micelles and served as a carrier for several
      hydrophobic anticancer drugs including DOX, PTX and C6-ceramide. POEG-b-PPPMP
      prodrug polymer exhibited intrinsic antitumor activity in vitro and in vivo. In
      addition, POEG-b-PPPMP prodrug polymer was comparable to free PPMP in selectively
      enhancing the production of pro-apoptotic ceramide species as well as down
      regulating the mRNA expression of GCS. DOX-loaded POEG-b-PPPMP micelles exhibited
      an excellent stability of 42 days at 4  degrees C. Moreover, DOX loaded in POEG-b
      PPPMP micelles showed higher levels of cytotoxicity than DOX loaded in a
      pharmacologically inert polymer (POEG-b-POM) and Doxil formulation in several
      tumor cell lines. Consistently, in a 4T1.2 murine breast cancer model, the tumor
      inhibition followed the order of DOX/POEG-b-PPPMP > DOX/POEG-b-POM >= Doxil >
      POEG-b-PPPMP > POEG-b-POM. Our data suggest that POEG-b-PPPMP micelles are a
      promising dual-functional carrier that warrants more studies in the future.

PMID- 30223049
TI  - Achyranthes aspera Linn. alleviates cerebral ischemia-reperfusion-induced
      neurocognitive, biochemical, morphological and histological alterations in Wistar
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional system of Indian medicine, the
      whole plant and roots of Achyranthes aspera L have been extensively used to treat
      neurological conditions such as epilepsy and stroke by the various ethnic
      communities of India. AIM OF THE STUDY: The present study was aimed to evaluate
      the cerebroprotective potential of methanol extract of A. aspera aerial parts
      (MeAA). MATERIALS AND METHODS: Initially the MeAA was evaluated for total
      phenolic content and subjected to detailed liquid chromatography-mass
      spectrometry analysis. Additionally, it was evaluated for in vitro antioxidant
      activity in ferric reducing antioxidant power, 2, 2-diphenyl-1-picrylhydrazyl and
      oxygen radical absorbance capacity assays. Furthermore, in RAW 264.7 cell lines
      the effect of MeAA was evaluated on lipopolysaccharide-induced generation of
      reactive oxygen species, nitrite and tumor necrosis factor-alpha. Finally, the
      MeAA (400 and 800 mg/kg) was evaluated against ischemia-reperfusion (I/R)-induced
      brain injury in rats. In brief, male Wistar rats were allocated in to five groups
      (G-I to G-V, n = 10). G-I and G-II assigned as sham control and I/R control, and
      received only vehicle (carboxy methyl cellulose 0.5% w/v, 10 ml/kg, p.o.). G-III
      received quercetin (20 mg/kg, p.o.) and assigned as reference standard. G-IV and
      G-V group animals received 400 and 800 mg/kg oral doses of MeAA, respectively.
      All the treatments were given orally for a period of seven days and the
      parameters such as functional (neurological, cognitive and motor), morphological
      (edema and infarct area), biochemical (superoxide dismutase, catalase, reduced
      glutathione, lipid peroxidation, cytokines), and histopathological evaluations of
      the brain tissue was performed. RESULTS: The MeAA exhibited 72.48 mg gallic acid
      equivalents/g of total phenolic content and the LC-MS/MS analysis showed
      acteoside, apigenin, and pentagalloyl glucose as major ingredients in the MeAA.
      In in vitro antioxidant assays, the MeAA showed good antioxidant activity with
      IC50 of 126.50 MUg/ml in DPPH assay; FRAP and ORAC values of 759.65 and 979.4 in
      FRAP and ORAC assays, respectively. Further, the MeAA significantly suppressed
      the generation of ROS, nitrite and TNF-alpha in LPS activated RAW 264.7 cell
      lines. Besides, sixty mins of global cerebral ischemia followed by 24 h of
      reperfusion produced considerable alterations in neurobehavioral functions in the
      I/R control group compared to sham control, with a significant reduction in
      catalase and superoxide dismutase enzyme activities. Moreover, there was a
      significant reduction in reduced glutathione levels with increased lipid
      peroxidation. Furthermore, the levels of pro-inflammatory cytokines (TNF-alpha,
      IL-6, and ICAM-I) increased significantly and those of anti-inflammatory (IL-10)
      decreased. I/R insult increased the brain volume and aggravated cerebral infarct
      formation. Histopathological examination of the brain tissue revealed vascular
      congestion, cerebral edema, leukocyte infiltration, and brain tissue necrosis.
      Interestingly, seven days pretreatment with MeAA (800 mg/kg, p.o.) has offered
      significant protection against I/R-induced functional, morphological, biochemical
      and histopathological alterations in Wistar rats. CONCLUSIONS: These findings
      suggest that the MeAA possesses potent cerebroprotective action through its
      antioxidant and anti-inflammatory mechanisms.

PMID- 30223048
TI  - Parental age and offspring leukocyte telomere length and attrition in midlife:
      Evidence from the 1946 British birth cohort.
AB  - BACKGROUND: There is evidence that paternal age may influence offspring telomere
      length, but the joint effects of father's and mother's age are unclear. We
      evaluated whether parental ages, individually and jointly, were associated with
      offspring telomere length and shortening. METHODS: We included 2305 British birth
      cohort participants with measured leukocyte telomere length (LTL) at age 53,
      among whom 941 had a second measurement at age 60-64. Linear regressions were
      performed to assess the associations of father's and mother's age at birth and
      the parental age gap, i.e. the difference between maternal and paternal age with
      LTL and LTL change. RESULTS: A one year increase in father's age corresponded to
      a 0.26% (95% CI: 0.04-0.47%) increase in offspring LTL at age 53 in the sex
      adjusted model. No association was observed for mother's age. Associations of
      father's or mother's age with offspring LTL at age 53 went to opposite directions
      when both parental ages were included together. For the difference in parental
      age, every year that fathers were older than mothers corresponded to a 0.94% (95%
      CI, 0.38-1.50%) increase in LTL at age 53 after adjustment for potential
      confounders. Neither parental ages nor the difference in parental ages were
      correlated with LTL change. CONCLUSION: There was a joint effect of parental ages
      on offspring telomere length, further denoting a complex role of reproductive age
      in offspring health and ageing.

PMID- 30223050
TI  - The influence of compatibility of Si-Ni decoction with metabolism in intestinal
      bacteria on transports of toxic diterpenoid alkaloids from processed aconite root
      across Caco-2 monolayers.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, processed
      aconite root (lateral root of Aconitum carmichaelii Debx.) is used as the
      principle herb of the Si-Ni decoction (SND) formula due to its cardiotonic
      effect, while its cardiotoxicity and neurotoxicity caused by diester and
      monoester diterpenoid alkaloids are reduced by compatibility of dried ginger and
      honey-processed liquorice in SND. AIM OF THE STUDY: To investigate the
      detoxification of processed aconite root by compatibility of SND from the
      perspective of intestinal absorption with metabolism in intestinal bacteria.
      MATERIALS AND METHODS: Decoctions of processed aconite root (AD), processed
      aconite root and honey-processed liquorice (ALD), and SND with the same amount of
      each herb were prepared, then were incubated in human intestinal bacteria juice
      (IBJ) in vitro for different durations. Bidirectional transmembrane transports of
      these decoctions and their IBJ-incubated decoctions were conducted on Caco-2
      monolayers. Correlation between efflux ratios changes of benzoylmesaconine,
      benzoylaconine, benzoylhypaconine (monoester-diterpenoid alkaloids, MDAs) and
      hypaconitine (diester-diterpenoid alkaloids) from processed aconite root, and
      metabolic trends of compounds from honey-processed liquorice and dried ginger
      were also performed. RESULTS: The absorption of MDAs from processed aconite root
      was increased by combination with honey-processed liquorice in ALD, but they were
      decreased significantly by the addition of dried ginger in SND. Take
      benzoylhypaconine for example, the Papp, AP to BL soared from (3.13 +/- 0.18) *
      10-7 cm/s in AD to (23.32 +/- 3.51) * 10-7 cm/s in ALD, while it dropped to (1.12
      +/- 0.17) * 10-7 cm/s in SND. When herb combined decoctions metabolised by
      intestinal bacteria for 12 h, the efflux ratio of benzoylhypaconine were both
      increased from 0.56 to 1.21 in ALD and from 1.10 to 2.61 in SND, which was
      correlative with the generation of davidigenin and glycyrrhetic acid (the
      metabolites of chalcones and pentacyclic triterpenoids from liquorice) in ALD and
      with the metabolism of [6]-gingerol (the major compound from dried ginger) in
      SND, respectively. CONCLUSIONS: Compatibility of SND altered the intestinal
      absorption of toxic MDAs and hypaconitine from processed aconite root. In SND,
      dried ginger rather than honey-processed liquorice played the role of
      detoxification of these toxic compounds in the intestinal absorption. The
      intestinal detoxification of SND was significantly and strongly correlative with
      metabolism of dried ginger and honey-processed liquorice by intestinal bacteria,
      simultaneously.

PMID- 30223051
TI  - Nigella sativa L. seed regulated eNOS, VCAM-1 and LOX-1 genes expression and
      improved vasoreactivity in aorta of diabetic rat.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Nigella sativa L. seed has been widely used in
      traditional medicine for the treatment of diabetes. The major reason for vascular
      complications in diabetic patients is endothelial dysfunction. However, the
      impact of N. sativa seed on endothelial dysfunction in diabetes remains unclear.
      AIM OF THE STUDY: This study was conducted to evaluate the effect of the
      hydroalcoholic extract of N. sativa seed on eNOS, VCAM-1, and LOX-1 genes
      expression and the vasoreactivity of aortic rings to acetylcholine (Ach) in
      streptozotocin (STZ)-induced diabetic rat. MATERIALS AND METHODS: Treated rats
      received N. sativa seed extract (100, 200, and 400 mg/kg) daily by gavage for 6
      weeks. The fasting blood glucose and lipids were measured and atherogenic index
      of plasma (AIP) was calculated. The endothelium-dependent vasoreactivity
      responses of isolated aortic rings were evaluated in the presence of cumulative
      concentrations of Ach (10-8-10-5 M). eNOS, VCAM-1, and LOX-1 genes expression in
      aortic tissue was assessed by using real time polymerase chain reaction (PCR).
      RESULTS: Male diabetic Wistar rats treated with N. sativa seed extract for six
      weeks reduced serum glucose and lipids and improved AIP. The vasorelaxant
      responses of aortic rings to Ach were markedly improved. N. sativa seed
      significantly increased eNOS in mRNA expression level and function, while it
      decreased VCAM-1 and LOX-1 expressions in vascular cells of aortic tissue which
      assessed only in mRNA level. CONCLUSIONS: The results of this study showed that
      N. sativa seed more likely, has antidiabetic and antihyperlipidemic properties
      and improved vasoreactivity, endothelial dysfunction, and vascular inflammation
      in diabetic rats' aorta.

PMID- 30223052
TI  - Structural characterization and anti-thrombotic properties of fucoidan from
      Nemacystus decipiens.
AB  - The sulfated polysaccharide NP2 was isolated and purified from Nemacystus
      decipiens, the structure and antithrombotic activity of NP2 was further studied.
      NP2 was composed of fucose, glucuronic acid, galactose and xylose at molar ratios
      of 76.3:20.5:1.5:1.7. ES-CID-MS/MS results showed that NP2 had a backbone of
      alpha (1 -> 3)-linked fucose and a branch was composed of Fuc-(2 -> 1)-GlcA,
      which was agree with the results of NMR and methylation analysis. The results
      also show that the sulfate groups were substituted at the C2 or C4 positions of
      the fucose residues. In addition, analysis of the antithrombotic activity results
      indicated that NP2 can increase the percentage of t-PA/PAI-1, thereby suggesting
      that NP2 has high fibrinolytic activity and should be explored as a novel
      antithrombotic agent.

PMID- 30223053
TI  - Marine bacterial chitinase as sources of energy, eco-friendly agent, and
      industrial biocatalyst.
AB  - Chitin is the richest renewable polymer carbohydrate in the marine environment
      and is an energetic source of nitrogen and carbon for marine organisms. Marine
      chitinolytic bacteria play a basic role in the nutrient cycling in the oceans by
      biodegradation of chitinous waste to useful form. Chitinase-producing bacteria
      from marine wastes increasing attention has received, and it serves two purposes:
      (i) reduce environmental hazards by waste management and (ii) increases
      generation of industrially important value-added products. This review aims to
      present the environmental pitfalls caused by marine waste and successes of
      chitinase-producing bacteria in employ waste for the generation of functional and
      valuable products, as well as to present importance role of chitinase-producing
      bacteria in industry. The focus is on isolation, purification, biochemical and
      enzymatic characteristics of chitinolytic bacteria in the oceans.

PMID- 30223054
TI  - Binding mechanism of lipase to Ligupurpuroside B extracted from Ku-Ding tea as
      studied by multi-spectroscopic and molecular docking methods.
AB  - The interaction of lipase with Ligupurpuroside B was studied by multiple
      spectroscopic techniques, enzyme activity and molecular modeling under simulative
      physiological condition. According to Stern-Volmer equation, fluorescence of
      lipase was quenched by Ligupurpuroside B via a static quenching mechanism because
      of formation of Ligupurpuroside B-lipase complex. Binding constants, number of
      binding sites & thermodynamic parameters were evaluated. The values of DeltaGo (
      25.085 kJ mol-1), DeltaHo (-12.14 kJ mol-1) and DeltaSo (+43.45 J mol-1 K-1) at
      298 K indicated that Ligupurpuroside B-lipase interaction is spontaneous and
      hydrophobic interaction is the main force stabilizing the Ligupurpuroside B
      lipase complex. The enzyme activity assay showed that Ligupurpuroside B inhibited
      lipase activity efficiently. Synchronous fluorescence spectra (SFS) suggested
      that Ligupurpuroside B is closer to Trp residues than to Tyr residues. All above
      experimental results were confirmed by molecular docking studies, which further
      indicated the binding site of Ligupurpuroside B on the surface of lipase, and the
      amino acid residues of lipase interacting with Ligupurpuroside B. Our present
      research work gives valuable information on the design of drugs with lipase as a
      carrier and should be useful for food industries.

PMID- 30223056
TI  - Synthesis of chemically crosslinked pullulan/gelatin-based extracellular matrix
      mimetic gels.
AB  - In order to develop pullulan/gelatin-based gels as potential extracellular matrix
      mimetic scaffolds, a "one-step" synthesis method using 1,1'-carbonyldiimidazole
      (CDI) as activator in DMSO under mild conditions was reported for the first time.
      Particularly, in contrast to conventional critical requirement of absolute
      dryness for CDI, it was interesting to find that the formation of gels could be
      accomplished in the presence of aqueous solvent within a much shorter time, while
      obtaining improved mechanical properties as demonstrated by compressive tests. UV
      Visible spectroscopy, NMR spectrum, TEM and SEM analysis have been employed to
      evaluate the underlying reaction mechanisms. This method implied that absolute
      dryness might not be necessary for using CDI as activator in certain cases. This
      method also represents a new rapid and efficient approach for synthesizing a
      great variety of chemically crosslinked polysaccharide/protein-based gels as
      promising material platform potential for tissue engineering and drug delivery
      applications.

PMID- 30223055
TI  - Assessment of gallic acid-modified fish gelatin formulations to optimize the
      mechanical performance of films.
AB  - In this study, a response surface methodology (RSM) using a Box-Behnken design
      was applied to optimize the mechanical response (tensile strength, elongation at
      break and Young's modulus) of fish gelatin films. These responses were analyzed
      as a function of glycerol content (0-10% on gelatin basis), added as a
      plasticizer, gallic acid content (5-15% on gelatin basis), used as crosslinker,
      and solution pH (4.5-10). Second order polynomial models were adjusted for the
      three responses, and they were found to be reliable according to the standard
      statistical analysis. The values of the independent factors that maximize the
      responses were also determined. In order to relate mechanical performance to
      material structure, Fourier transform infrared (FTIR) analysis was carried out
      and this revealed that a reaction occurs between gelatin and gallic acid through
      a process that releases water and provides a plasticizing effect. The performed
      time-, material- and cost-saving optimization of the formulation based on
      biodegradable compounds from abundant renewable resources enabled a sustainable
      approach to the development of new materials.

PMID- 30223057
TI  - Heating and cysteine effect on physicochemical and flavor properties of soybean
      peptide Maillard reaction products.
AB  - Maillard reaction products (MRPs) were obtained by using the xylose and soybean
      peptide system through a 2 h heating at pH of 7.6. Cysteine addition and thermal
      treatment at 80, 100, 120 and 140  degrees C were investigated via E-nose and E
      tongue, free amino acids (FAA) and GC-MS analyses of MRPs. Afterwards, the
      combined effects were performed using the partial least square regression (PLSR).
      Results suggested that MRPs without cysteine addition (XSs) had stronger browning
      intensity, and the cysteine would be beneficial to the pH reduction with heating
      temperature increasing. PLSR analysis revealed that MRPs with cysteine addition
      heated at 140  degrees C (XSC-140) showed the lowest bitterness, and XS-100 had
      the highest umami and saltiness. Both bitter and umami FAA increased with the
      addition of cysteine, and more furans and nitrogen-containing compounds formed in
      the XSs brought caramel-like flavor, while XSCs exhibited meat-like flavor
      attributed to sulphides generation.

PMID- 30223058
TI  - Purification and characterization of a thermo-acid/alkali stable xylanases from
      Aspergillus oryzae LC1 and its application in Xylo-oligosaccharides production
      from lignocellulosic agricultural wastes.
AB  - Xylooligosaccharides (XOS) from lignocellulosic biomass (LCB) have found
      widespread applications in food, feed, nutraceuticals and pharamecutical
      industries. Enzymatic degradation of LCB for generation of XOS have gained
      impetus in recent times In the present investigation an extracellular thermo
      alkali stable xylanase from Aspergillus oryzae LC1 was purified by using PEG
      8000/MgSO4 aqueous two-phase system and was capable of hydrolysing various
      agricultural residues into XOS system. Highest activity was observed using 11.3%
      (w/w) PEG 8000 and 22.5% (w/w) sulphate salt with maximum purification factor (13
      fold), highest yield (86.8%) and partition coefficient (8.8%). The purification
      of the crude enzyme also resulted in decrement of beta-xylosidase activity (29.8
      U/mL to 0.6 U/mL). The molecular weight of enzyme was estimated ~35 kDa. The
      highest residual activity was obtained with birch wood xylan as substrate with Km
      and Vmax of 0.2 mg/mL and 172.2 MUmol min-1 mg-1 respectively. The metal ions
      Fe2+, Ag2+, Mg2+, Mn+ and Co+ enhanced xylanase activity while EDTA, DMSO and SDS
      acted as inhibitor. The effect of Fe+2 was confirmed by the circular dichroism
      experiment. The partially purified enzyme was capable of generating XOS i.e.
      xylobiose (0.68 mg/g), xylotriose (2.47 mg/g) and xylotetraose (2.29 mg/g) by
      direct enzymatic hydrolysis of untreated sugarcane baggase, wheat straw and wheat
      bran respectively.

PMID- 30223059
TI  - Oculomotor inhibition reflects temporal expectations.
AB  - The accurate extraction of signals out of noisy environments is a major challenge
      of the perceptual system. Forming temporal expectations and continuously matching
      them with perceptual input can facilitate this process. In humans, temporal
      expectations are typically assessed using behavioral measures, which provide only
      retrospective but no real-time estimates during target anticipation, or by using
      electrophysiological measures, which require extensive preprocessing and are
      difficult to interpret. Here we show a new correlate of temporal expectations
      based on oculomotor behavior. Observers performed an orientation-discrimination
      task on a central grating target, while their gaze position and EEG were
      monitored. In each trial, a cue preceded the target by a varying interval
      ("foreperiod"). In separate blocks, the cue was either predictive or non
      predictive regarding the timing of the target. Results showed that saccades and
      blinks were inhibited more prior to an anticipated regular target than a less
      anticipated irregular one. This consistent oculomotor inhibition effect enabled a
      trial-by-trial classification according to interval-regularity. Additionally, in
      the regular condition the slope of saccade-rate and drift were shallower for
      longer than shorter foreperiods, indicating their adjustment according to
      temporal expectations. Comparing the sensitivity of this oculomotor marker with
      those of other common predictability markers (e.g. alpha-suppression) showed that
      it is a sensitive marker for cue-related anticipation. In contrast, temporal
      changes in conditional probabilities (hazard-rate) modulated alpha-suppression
      more than cue-related anticipation. We conclude that pre-target oculomotor
      inhibition is a correlate of temporal predictions induced by cue-target
      associations, whereas alpha-suppression is more sensitive to conditional
      probabilities across time.

PMID- 30223060
TI  - Hard to wake up? The cerebral correlates of sleep inertia assessed using combined
      behavioral, EEG and fMRI measures.
AB  - The first minutes following awakening from sleep are typically marked by reduced
      vigilance, increased sleepiness and impaired performance, a state referred to as
      sleep inertia. Although the behavioral aspects of sleep inertia are well
      documented, its cerebral correlates remain poorly understood. The present study
      aimed at filling this gap by measuring in 34 participants the changes in
      behavioral performance (descending subtraction task, DST), EEG spectral power,
      and resting-state fMRI functional connectivity across three time points: before
      an early-afternoon 45-min nap, 5 min after awakening from the nap and 25 min
      after awakening. Our results showed impaired performance at the DST at awakening
      and an intrusion of sleep-specific features (spectral power and functional
      connectivity) into wakefulness brain activity, the intensity of which was
      dependent on the prior sleep duration and depth for the functional connectivity
      (14 participants awakened from N2 sleep, 20 from N3 sleep). Awakening in N3
      (deep) sleep induced the most robust changes and was characterized by a global
      loss of brain functional segregation between task-positive (dorsal attention,
      salience, sensorimotor) and task-negative (default mode) networks. Significant
      correlations were observed notably between the EEG delta power and the functional
      connectivity between the default and dorsal attention networks, as well as
      between the percentage of mistake at the DST and the default network functional
      connectivity. These results highlight (1) significant correlations between EEG
      and fMRI functional connectivity measures, (2) significant correlations between
      the behavioral aspect of sleep inertia and measures of the cerebral functioning
      at awakening (both EEG and fMRI), and (3) the important difference in the
      cerebral underpinnings of sleep inertia at awakening from N2 and N3 sleep.

PMID- 30223061
TI  - Normative pathways in the functional connectome.
AB  - Functional connectivity is frequently derived from fMRI data to reduce a complex
      image of the brain to a graph, or "functional connectome". Often shortest-path
      algorithms are used to characterize and compare functional connectomes. Previous
      work on the identification and measurement of semi-metric (shortest circuitous)
      pathways in the functional connectome has discovered cross-sectional differences
      in major depressive disorder (MDD), autism spectrum disorder (ASD), and
      Alzheimer's disease. However, while measurements of shortest path length have
      been analyzed in functional connectomes, less work has been done to investigate
      the composition of the pathways themselves, or whether the edges composing
      pathways differ between individuals. Developments in this area would help us
      understand how pathways might be organized in mental disorders, and if a
      consistent pattern can be found. Furthermore, studies in structural brain
      connectivity and other real-world graphs suggest that shortest pathways may not
      be as important in functional connectivity studies as previously assumed. In
      light of this, we present a novel measurement of the consistency of pathways
      across functional connectomes, and an algorithm for improvement by selecting the
      most frequently occurring "normative pathways" from the k shortest paths, instead
      of just the shortest path. We also look at this algorithm's effect on various
      graph measurements, using randomized matrix simulations to support the efficacy
      of this method and demonstrate our algorithm on the resting-state fMRI (rs-fMRI)
      of a group of 34 adolescent control participants. Additionally, a comparison of
      normative pathways is made with a group of 82 age-matched participants, diagnosed
      with MDD, and in doing so we find the normative pathways that are most disrupted.
      Our results, which are carried out with estimates of connectivity derived from
      correlation, partial correlation, and normalized mutual information connectomes,
      suggest disruption to the default mode, affective, and ventral attention
      networks. Normative pathways, especially with partial correlation, make greater
      use of critical anatomical pathways through the striatum, cingulum, and the
      cerebellum. In summary, MDD is characterized by a disruption of normative
      pathways of the ventral attention network, increases in alternative pathways in
      the frontoparietal network in MDD, and a mixture of both in the default mode
      network. Additionally, within- and between-groups findings depend on the estimate
      of connectivity.

PMID- 30223062
TI  - Nuisance effects and the limitations of nuisance regression in dynamic functional
      connectivity fMRI.
AB  - In resting-state fMRI, dynamic functional connectivity (DFC) measures are used to
      characterize temporal changes in the brain's intrinsic functional connectivity. A
      widely used approach for DFC estimation is the computation of the sliding window
      correlation between blood oxygenation level dependent (BOLD) signals from
      different brain regions. Although the source of temporal fluctuations in DFC
      estimates remains largely unknown, there is growing evidence that they may
      reflect dynamic shifts between functional brain networks. At the same time,
      recent findings suggest that DFC estimates might be prone to the influence of
      nuisance factors such as the physiological modulation of the BOLD signal.
      Therefore, nuisance regression is used in many DFC studies to regress out the
      effects of nuisance terms prior to the computation of DFC estimates. In this work
      we examined the relationship between seed-specific sliding window correlation
      based DFC estimates and nuisance factors. We found that DFC estimates were
      significantly correlated with temporal fluctuations in the magnitude (norm) of
      various nuisance regressors. Strong correlations between the DFC estimates and
      nuisance regressor norms were found even when the underlying correlations between
      the nuisance and fMRI time courses were relatively small. We then show that
      nuisance regression does not necessarily eliminate the relationship between DFC
      estimates and nuisance norms, with significant correlations observed between the
      DFC estimates and nuisance norms even after nuisance regression. We present
      theoretical bounds on the difference between DFC estimates obtained before and
      after nuisance regression and relate these bounds to limitations in the efficacy
      of nuisance regression with regards to DFC estimates.

PMID- 30223064
TI  - Modeling missing binary outcome data while preserving transitivity assumption
      yielded more credible network meta-analysis results.
AB  - OBJECTIVES: The objectives of this study were to elaborate on the conceptual
      evaluation of transitivity assumption in the context of binary missing
      participant outcome data (MOD) in network meta-analysis (NMA) and to emphasize on
      the importance of statistical modeling as a mean to address MOD. STUDY DESIGN AND
      SETTING: We designate the notion of transitivity assumption in the context of
      binary MOD and indicate scenarios that compromise transitivity in complex
      networks. We propose a modification of these scenarios that preserves
      transitivity assumption. Using a published NMA, we indicate the implications of
      excluding or imputing, rather than modeling MOD, on NMA findings. RESULTS: Arm
      specific scenarios for MOD, as commonly applied in conventional meta-analysis,
      compromise the validity of transitivity assumption in complex networks. The
      motivating example reveals that imputation of those scenarios yields estimates in
      the opposite direction for the basic parameters with narrower credible intervals
      and inflates between-trial variance. Contrariwise, modeling MOD after
      modification of the scenarios yields robust estimates for the basic parameters
      but wider credible intervals and reduces between-trial variance. CONCLUSION:
      Application of arm-specific scenarios for binary MOD requires modification in
      complex networks to ensure valid transitivity assumption. Analysts should model,
      rather than exclude or impute MOD, to provide bias-adjusted results.

PMID- 30223065
TI  - How variation in predictor measurement affects the discriminative ability and
      transportability of a prediction model.
AB  - BACKGROUND AND OBJECTIVE: Diagnostic and prognostic prediction models often
      perform poorly when externally validated. We investigate how differences in the
      measurement of predictors across settings affect the discriminative power and
      transportability of a prediction model. METHODS: Differences in predictor
      measurement between data sets can be described formally using a measurement error
      taxonomy. Using this taxonomy, we derive an expression relating variation in the
      measurement of a continuous predictor to the area under the receiver operating
      characteristic curve (AUC) of a logistic regression prediction model. This
      expression is used to demonstrate how variation in measurements across settings
      affects the out-of-sample discriminative ability of a prediction model. We
      illustrate these findings with a diagnostic prediction model using example data
      of patients suspected of having deep venous thrombosis. RESULTS: When a
      predictor, such as D-dimer, is measured with more noise in one setting compared
      to another, which we conceptualize as a difference in "classical" measurement
      error, the expected value of the AUC decreases. In contrast, constant,
      "structural" measurement error does not impact on the AUC of a logistic
      regression model, provided the magnitude of the error is the same among cases and
      noncases. As the differences in measurement methods between settings (and in turn
      differences in measurement error structures) become more complex, it becomes
      increasingly difficult to predict how the AUC will differ between settings.
      CONCLUSION: When a prediction model is applied to a different setting to the one
      in which it was developed, its discriminative ability can decrease or even
      increase if the magnitude or structure of the errors in predictor measurements
      differ between the two settings. This provides an important starting point for
      researchers to better understand how differences in measurement methods can
      affect the performance of a prediction model when externally validating or
      implementing it in practice.

PMID- 30223063
TI  - Decoding motion direction using the topography of sustained ERPs and alpha
      oscillations.
AB  - The present study sought to determine whether scalp electroencephalogram (EEG)
      signals contain decodable information about the direction of motion in random dot
      kinematograms (RDKs), in which the motion information is spatially distributed
      and mixed with random noise. Any direction of motion from 0 to 360 degrees  was
      possible, and observers reported the precise direction of motion at the end of a
      1500-ms stimulus display. We decoded the direction of motion separately during
      the motion period (during which motion information was being accumulated) and the
      report period (during which a shift of attention was necessary to make a fine
      tuned direction report). Machine learning was used to decode the precise
      direction of motion (within +/-11.25 degrees ) from the scalp distribution of
      either alpha-band EEG activity or sustained event-related potentials (ERPs). We
      found that ERP-based decoding was above chance (1/16) during both the stimulus
      and the report periods, whereas alpha-based decoding was above chance only during
      the report period. Thus, sustained ERPs contain information about spatially
      distributed direction-of-motion, providing a new method for observing the
      accumulation of sensory information with high temporal resolution. By contrast,
      the scalp topography of alpha-band EEG activity appeared to mainly reflect
      spatially focused attentional processes rather than sensory information.

PMID- 30223066
TI  - Regulation of sex hormone receptors in sexual dimorphism of human cancers.
AB  - Gender differences in the incidences of cancers have been found in almost all
      human cancers. However, the mechanisms that underlie gender disparities in most
      human cancer types have been under-investigated. Here, we provide a comprehensive
      overview of potential mechanisms underlying sexual dimorphism of each cancer
      regarding sex hormone signaling. Fully addressing the mechanisms of sexual
      dimorphism in human cancers will greatly benefit current development of precision
      medicine. Our discussions of potential mechanisms underlying sexual dimorphism in
      each cancer will be instructive for future cancer research on gender disparities.

PMID- 30223067
TI  - Application of liquid biopsy in bone and soft tissue sarcomas: Present and
      future.
AB  - Bone and soft tissue sarcomas account for approximately 1% of adult solid
      malignancies and 20% of pediatric solid malignancies. Sarcomas are divided into
      more than 50 subtypes. Each subtype is highly heterogeneous and characterized by
      significant morphological and phenotypic variability. Currently, sarcoma
      characterization is based on tissue biopsies. However, primary and invasive
      tissue biopsies may not accurately reflect the current disease condition
      following treatment as is may cause marked changes to the tumor cells. Liquid
      biopsy offers an alternative minimally invasive approach to provide dynamic tumor
      information, allowing for the application of precision medicine in the treatment
      of sarcomas. Recently, there have been numerous blood-based tumor components
      identified by liquid biopsy in sarcomas, including circulating tumor cells,
      circulating cell-free nucleic acids, tumor-derived exosomes and metabolites in
      circulation. Here, we summarize the current evolving technologies and then
      elaborate on emerging novel concepts that may further propel the field of liquid
      biopsy in sarcomas. We address the applications in the context of our current
      knowledge about liquid biopsy in sarcomas and highlight the potential of
      translating these recent advances into the clinic for more effective management
      strategies for sarcoma patients.

PMID- 30223068
TI  - Single-cell RNA sequencing reveals diverse intratumoral heterogeneities and gene
      signatures of two types of esophageal cancers.
AB  - Single-cell RNA sequencing and transcriptome analysis enable novel discovery and
      precise characterization of new cell types and states, which improves the
      understanding of the cellular context of tumorigenesis. Herein, we applied this
      powerful approach to analyze 368 single cells from three esophageal squamous cell
      carcinoma (ESCC) and two esophageal adenocarcinoma (EAC) tumors. Using inferred
      copy number variation analysis, we successfully distinguished carcinoma cells
      from heterogeneous cellular populations, identifying gene signatures and crucial
      cancer-related signaling pathways related to ESCC and EAC. In particular, we
      found that NOTCH signaling was exclusively activated in ESCC, but not in EAC.
      ESCC tumors with higher NOTCH activity were associated with significantly worse
      survival rates than those with lower NOTCH activity. Collectively, this study
      revealed that ESCC and EAC are distinct in terms of cellular transcriptome
      profiles, which leads to a wide range of intratumoral cellular heterogeneity. The
      findings suggest that different therapeutic strategies that target the
      differences between two types of esophageal cancers are required, guiding cancer
      specific future drug development.

PMID- 30223069
TI  - Targeting antioxidant enzymes as a radiosensitizing strategy.
AB  - Radiotherapy represents a major anti-cancer modality and effectively kills cancer
      cells through generation of reactive oxygen species (ROS). However, cancer cells
      are commonly characterized by increased activity of ROS-scavenging enzymes in
      adaptation to intrinsic oxidative stress, leading to radioresistance. Abrogation
      of this defense network by pharmacological ROS insults therefore is shown to
      improve radioresponse in preclinical models; some of them are then tested in
      clinical trials. In this review, we address (1) the importance of ROS in
      radioresponse, (2) the main systems regulating redox homeostasis with a special
      focus on their prognostic effect and predictive role in radiotherapy, and (3) the
      potential radiosensitizers acting through inhibition of antioxidant enzymes.

PMID- 30223070
TI  - Metastasis of breast tumor cells to brain is suppressed by targeting RLIP alone
      and in combination with 2'-Hydroxyflavanone.
AB  - Brain metastasis is an important cause of morbidity and mortality in cancer
      patients. Breast tumor cells frequently metastasize to brain and initiate severe
      therapeutic complications. In the present study, we evaluated the anti-metastatic
      effects of 2'-hydroxyflavanone (2HF) alone and in combination with RLIP targeted
      therapy in a novel murine model of breast tumor metastasis. The MDA-MB231Br
      (brain-seeking) breast cancer (BC) cells stably-transfected with luciferase were
      injected into the left-ventricle of NSG mouse heart and the migration of cells to
      brain was monitored using a non-invasive bioluminescent imaging system. To
      evaluate the tumor growth suppressive effects, mice were given 2HF (50 mg/kg,
      b.w., alternate days orally), RLIP-antibody (Rab; 5 mg/kg, b.w., weekly i.p.) or
      combination of 2HF+Rab starting day1 after intra-cardiac injection. Our results
      reveal that 2HF and Rab significantly prevented the metastasis of BC cells to
      brain. Further, mice treated with combination of 2HF+Rab exhibited no metastasis
      as compared to either or the single agent-treated mice. This study for the first
      time demonstrates the anti-metastatic effects of 2HF and RLIP-inhibition in-vivo
      in a novel breast tumor metastasis model and provides the rationale for further
      clinical investigation.

PMID- 30223071
TI  - Estimation of total prescription weights of active pharmaceutical ingredients in
      human medicines based on a public database for environmental risk assessment in
      Japan.
AB  - The distribution of active pharmaceutical ingredients (APIs) in prescription
      medicines for human consumption in Japan was estimated using the public database
      of the National Database of Health Insurance Claims and Specific Health Checkups
      of Japan (NDB). From the latest NDB, 2058 APIs were identified, and the
      prescription weight exceeded 1 tonne/year for 711 APIs. Of these, 298 APIs were
      selected for further analysis after removing 413 APIs that were not covered by
      current environmental risk assessment (ERA) directives or were combination
      products. Among the 298 APIs, 43 were relatively newly branded APIs that have
      been available on the Japanese market since 2001 or later and have no generic
      drugs, and only 5 of the branded APIs are used by more than 1% of the population.
      When prescription data from the 47 prefectures in Japan were analyzed,
      prescription weights for 257 of the 298 APIs were the highest in Tokyo, probably
      because of its large population. Though it has both advantages and limitations,
      this novel method based on a non-profit public database can provide a
      transparent, unbiased and cost-effective solution for the estimation of the
      environmental exposure of generic and branded human medicines distributed with
      prescriptions in Japan.

PMID- 30223072
TI  - A review on arsenic carcinogenesis: Epidemiology, metabolism, genotoxicity and
      epigenetic changes.
AB  - Long-term exposure to arsenic (inorganic arsenic) is a world-wide environmental
      health concern. Arsenic is classified as the Group 1 human carcinogen by the
      International Agency for Research on Cancer (IARC). Epidemiological studies have
      established a strong association between inorganic arsenic (iAs) exposure in
      drinking water and an increased incidence of cancer including bladder, liver,
      lung, prostate, and skin cancer. iAs also increases the risk of other diseases
      such as cardiovascular disease, hypertension and diabetes. The molecular
      mechanisms of carcinogenesis of iAs remain poorly defined, several mechanisms
      have been proposed, including genotoxicity, altered cell proliferation, oxidative
      stress, changes to the epigenome, disturbances of signal transduction pathways,
      cytotoxicity and regenerative proliferation. In this article, we will summarize
      current knowledge on the mechanisms of arsenic carcinogenesis and focus on
      integrating all these issues to garner a broader perspective.

PMID- 30223073
TI  - Sensory irritation of vapours of formic, acetic, propionic and butyric acid.
AB  - In mice, inhalation of formic, acetic, propionic and butyric acid caused a rapid
      decrease in the respiratory rate, which decreased to a stable level during the
      remaining part of the 30 min exposure period; this was due to sensory irritation.
      The concentration decreasing the respiratory rate (RD) by 50% (RD50) was 438,
      308, 386 and 285 ppm, respectively, which allowed an adequate prediction of the
      Threshold Limit Values. In mice inhaling through a tracheal cannula, bypassing
      the trigeminal nerves, caused a slower decrease in respiratory rate due to
      pulmonary irritation. In the low concentration range, the pulmonary irritation
      response was less pronounced than the sensory irritation response. As the
      response in the normal (non-cannulated) mice was not influenced by pulmonary
      irritation, sensory irritation is the key effect, presumably due to the scrubbing
      effect of the upper airways, preventing access to the lungs. The activated
      receptors were in a non-lipophilic (hydrophilic) environment, from where the
      receptors may be activated by means of liberated protons. At the RD0, formic acid
      may, at least partly, activates ASIC, TRPV1 and TRPA1 receptors, whereas acetic,
      propionic and butyric acid may activate ASIC and TRPA1 receptors, based on the
      estimated pH in the mucus layer.

PMID- 30223074
TI  - Investigations on the interactions between curcumin loaded vitamin E TPGS coated
      nanodiamond and Caco-2 cell monolayer.
AB  - This study aimed at investigating the potential mechanism of improved
      transportation of the curcumin loaded D-alpha-tocopherol polyethylene glycol 1000
      succinate coated nanodiamonds system (NDs/CUR/TPGS complexes) using an in vitro
      Caco-2 cell monolayer model. The core-shell structured NDs/CUR/TPGS nanocomplexes
      were 196.32 +/- 5.76 nm in size, with a high loading efficiency of 81.59 +/-
      3.42%. Cytotoxicity results suggested that the blank NDs did not induce any
      serious toxicity on Caco-2 cells even after incubated for 72 h. The cell
      viability for all the series of CUR loaded preparations was found to follow the
      sequence of CUR suspension > NDs/CUR > NDs/CUR/TPGS. Confocal laser fluorescence
      microscopy (CLSM) and flow cytometry system (FACS) studies confirmed that the
      cellular uptake of NDs could be efficiently enhanced by TPGS decoration. The
      transport mechanism of NDs/CUR and TPGS coated ones was mainly through an energy
      dependent, clathrin-mediated and caveolin-mediated endocytosis, and the
      endocytosis of NDs/CUR was also via macropinocytosis. Furthermore, the Papp value
      (AP-BL) of NDs/CUR and NDs/CUR/TPGS was 2.09- and 3.86-fold higher than that of
      the CUR suspension. All the results demonstrated that the pharmacological
      activates and intestinal permeability of CUR across Caco-2 cell monolayer was
      greatly enhanced by NDs/CUR/TPGS nanocomplexes. Thus NDs could be a promising
      oral drug delivery platform for improving the intestinal permeability and oral
      bioavailability of poorly soluble drugs.

PMID- 30223076
TI  - Facile marriage of Gd3+ to polymer-coated carbon nanodots with enhanced
      biocompatibility for targeted MR/fluorescence imaging of glioma.
AB  - Overcoming blood-brain barrier (BBB) for precise glioma diagnosis remains an
      urgent challenge due to its peculiar location in central nervous system (CNS).
      Herein, polymer-coated carbon nanodots with high hydrophilicity were facilely
      married with Gd-DTPA to construct a dual-modal imaging system (NCDDG). This
      system was demonstrated with obviously decreased toxicity and enhanced magnetic
      resonance imaging (MRI) ability compared to traditional Gd-DTPA. Meanwhile, NCDDG
      reserved the bright fluorescence of biocompatible carbon nanodots with increased
      spatial resolution. Attributed to small size and hydrophilic polymer coating,
      NCDDG was capable of overcoming the BBB and permeating leaky microvascular walls
      into surrounding glioma tissues via prolonged in vivo circulation and enhanced
      retention effect. As a result, dual1-modal targeted MR/fluorescence imaging of
      glioma was synergistically achieved with high sensitivity and resolution. This
      work promised a potential contrast agent for sensitive clinical diagnosis of
      glioma.

PMID- 30223077
TI  - The mechanism behind the biphasic pulsatile drug release from physically mixed
      poly(dl-lactic(-co-glycolic) acid)-based compacts.
AB  - Successful immunization often requires a primer, and after a certain lag time, a
      booster administration of the antigen. To improve the vaccinees' comfort and
      compliance, a single-injection vaccine formulation with a biphasic pulsatile
      release would be preferable. Previous work has shown that such a release profile
      can be obtained with compacts prepared from physical mixtures of various poly(dl
      lactic(-co-glycolic) acid) types (Murakami et al., 2000). However, the mechanism
      behind this release profile is not fully understood. In the present study, the
      mechanism that leads to this biphasic pulsatile release was investigated by
      studying the effect of the glass transition temperature (Tg) of the polymer, the
      temperature of compaction, the compression force, the temperature of the release
      medium, and the molecular weight of the incorporated drug on the release
      behavior. Compaction resulted in a porous compact. Once immersed into release
      medium with a temperature above the Tg of the polymer, the drug was released by
      diffusion through the pores. Simultaneously, the polymer underwent a transition
      from the glassy state into the rubbery state. The pores were gradually closed by
      viscous flow of the polymer and further release was inhibited. After a certain
      period of time, the polymer matrix ruptured, possibly due to a build-up in
      osmotic pressure, resulting in a pulsatile release of the remaining amount of
      drug. The compression force and the molecular weight of the incorporated drug did
      not influence the release profile. Understanding this mechanism could contribute
      to further develop single-injection vaccines.

PMID- 30223075
TI  - Synergy of nebulized phage PEV20 and ciprofloxacin combination against
      Pseudomonas aeruginosa.
AB  - Nebulization is currently used for delivery of antibiotics for respiratory
      infections. Bacteriophages (or phages) are effective predators of pathogens
      including Pseudomonas aeruginosa commonly found in the lungs of patients with
      cystic fibrosis (CF). It is known that phages and antibiotics can potentially
      show synergistic antimicrobial effect on bacterial killing. In the present study,
      we investigated synergistic antimicrobial effect of phage PEV20 with five
      different antibiotics against three P. aeruginosa strains isolated from sputum of
      CF patients. The antibiotics included ciprofloxacin, tobramycin, colistin,
      aztreonam and amikacin, which are approved by U.S Food and Drug Administration
      (FDA) for inhaled administration. Phage and antibiotic synergy was determined by
      assessing bacterial killing performing time-kill studies. Among the different
      phage-antibiotic combinations, PEV20 and ciprofloxacin exhibited the most
      synergistic effect. Two phage-ciprofloxacin combinations, containing 1/4 and 1/2
      of the minimum inhibitory concentration (MIC) of ciprofloxacin against P.
      aeruginosa strains FADD1-PA001 (A) and JIP865, respectively were aerosolized
      using both air-jet and vibrating mesh nebulizers and the synergistic
      antibacterial activity was maintained after nebulization. Air-jet nebulizer
      generated droplets with smaller volume median diameters (3.6-3.7 um) and slightly
      larger span (2.3-2.4) than vibrating mesh nebulizers (5.1-5.3 um; 2.1-2.2),
      achieving a higher fine particle fraction (FPF) of 70%. In conclusion, nebulized
      phage PEV20 and ciprofloxacin combination shows promising antimicrobial and
      aerosol characteristics for potential treatment of respiratory tract infections
      caused by drug-resistant P. aeruginosa.

PMID- 30223078
TI  - Correlation between molecular dynamics and physical stability of two milled
      anhydrous sugars: Lactose and sucrose.
AB  - The process of milling often results in amorphization and the physical stability
      of amorphous phase is linked with its molecular dynamics. This study focuses on a
      propensity of two disaccharides (lactose and sucrose) to amorphize on ball
      milling and the stability of the resultant amorphous phase. The amorphous content
      in milled sugars is estimated by Differential Scanning Calorimetry (DSC) and the
      stability was measured in terms of the tendency to recrystallize by Broadband
      Dielectric Spectroscopy (BDS). The results show that the amorphous content
      increases with milling time and is greater for lactose than sucrose. At the same
      degree of amorphization, sucrose recrystallize at temperature ~15  degrees C
      higher than lactose, indicating higher stability. The molecular dynamics (beta
      relaxation process), suggest that milled sucrose is more stable with higher
      activation energy (~9 kJ mol-1) than that of lactose. The moisture content of
      amorphous phase also impacts its molecular dynamics in terms of increase in
      activation energy as the moisture decrease with increasing the milling times. The
      study suggests a greater stability of amorphous sucrose and susceptibility of
      milled lactose to recrystallize, however, on extended milling when the moisture
      content decreases, lactose was seen to become relatively more stable.

PMID- 30223079
TI  - Engineering of pharmaceutical cocrystals in an excipient matrix: Spray drying
      versus hot melt extrusion.
AB  - The comparison of spray drying versus hot melt extrusion (HME) in order to
      formulate amorphous solid dispersions has been widely studied. However, to the
      best of our knowledge, the use of both techniques to form cocrystals within a
      carrier excipient has not previously been compared. The combination of ibuprofen
      (IBU) and isonicotinamide (INA) in a 1:1 M ratio was used as a model cocrystal. A
      range of pharmaceutical excipients was selected for processing - mannitol,
      xylitol, Soluplus and PVP K15. The ratio of cocrystal components to excipient was
      altered to assess the ratios at which cocrystal formation occurs during spray
      drying and HME. Hansen Solubility Parameter (HSP) and the difference in HSP
      between the cocrystal and excipient (DeltaHSP) was employed as a tool to predict
      cocrystal formation. During spray drying, when the difference in HSP between the
      cocrystal and the excipient was large, as in the case of mannitol (DeltaHSP of
      18.3 MPa0.5), a large amount of excipient (up to 50%) could be incorporated
      without altering the integrity of the cocrystal, whereas for Soluplus and PVP
      K15, where the DeltaHSP was 2.1 and 1.6 MPa0.5 respectively, the IBU:INA
      cocrystal alone was only formed at a very low weight ratio of excipient, i.e.
      cocrystal:excipient 90:10. Remarkably different results were obtained in HME. In
      the case of Soluplus and PVP K15, a mixture of cocrystal with single components
      (IBU and INA) was obtained even when only 10% excipient was included. In
      conclusion, in order to reduce the number of unit operations required to produce
      a final pharmaceutical product, spray drying showed higher feasibility over HME
      to produce cocrystals within a carrier excipient.

PMID- 30223080
TI  - Application of a chromatic confocal measurement system as new approach for in
      line wet film thickness determination in continuous oral film manufacturing
      processes.
AB  - The key parameter of the oral film production process is the wet film thickness
      since it regulates the active pharmaceutical ingredient (API) content of the
      finished product. There is no general recommendation on how to adjust the gap
      height of the coating knife during the film manufacturing process to obtain the
      target content. Therefore, trial and error approaches are common to determine the
      surplus of drug for every newly developed formulation. This wastes resources,
      money and time and calls for an adequate in-line tool for wet film thickness
      measurement during the film manufacturing process to ensure consistent quality.
      In this work, a chromatic confocal optical probe was implemented into a
      continuous oral film manufacturing process on a pilot-scale coating bench. The
      optical probe allows a non-destructive and contactless wet film thickness
      measurement. The validation of the method showed good results. Linearity was
      demonstrated over a wide range of film thicknesses (R2 = 0.999). A good precision
      between different films was revealed by a coefficient of variation smaller than
      2%. The robustness investigations showed that the method is applicable for
      transparent and non-transparent film forming masses. Furthermore, coloring
      agents, particles in the polymer mass and different viscosities do not influence
      the thickness measurement.

PMID- 30223081
TI  - Analysis of glucosyltransferase gene expression of clinical isolates of
      Streptococcus mutans obtained from dental plaques in response to sub-lethal doses
      of photoactivated disinfection.
AB  - BACKGROUND: Dental caries is a disease caused by a group of oral streptococcal
      microorganisms, primarily Strptococcus mutans. Photoactivated disinfection (PAD)
      has been proposed as a conservative method for treatment of carious lesions.
      Therefore, the aim of this study was to assess the effectiveness of indocyanine
      green (ICG)- and toluidine blue O (TBO)-PAD as supplementary tools in reducing
      the bacterial load and expression profiling of the gene associated with the
      biofilm formation in S. mutans. MATERIALS AND METHODS: S. mutans strains were
      isolated from dental plaque samples collected from 212 patients through
      conventional biochemical tests and molecular methods. After identification, S.
      mutans strains were photosensitized in vitro with TBO and ICG, which were excited
      at a specific light wavelength based on the photosensitizer. After evaluating
      doses of TBO- and ICG-PAD contributing to sub-significant reduction of CFU/mL,
      ROS levels were measured with DCFH-DA fluorescent probe. Eventually, TBO- and ICG
      PAD effects on the gtfB gene expression were assessed using real-time
      quantitative reverse transcription polymerase chain reaction. RESULTS: S. mutans
      strains were isolated from 50 (23.5%) patients. In this study, maximum doses of
      TBO- and ICG-PAD contributing to sub-significant reduction of CFU/mL against S.
      mutans strains were 23.12 MUM/mL TBO at fluence of 68.75 J/cm2 and 20.15 MUM/mL
      ICG at fluence of 31.2 J/cm2. According to the results, 3.8- and 6.1-fold
      increases in the fluorescence were observed in ICG and TBO treated cells compared
      to the control, respectively. The expression of gtfB was down regulated to
      approximately 3.9- and 8.25-fold following treatment with TBO- and ICG-PAD,
      respectively. CONCLUSIONS: The gtfB gene expression profiling decreased in the
      bacterial cells, with ICG-PAD causing a greater reduction. PAD may be a promising
      therapy for dentinal carious lesions.

PMID- 30223082
TI  - Walking under the influence of the alcohol: A case study of pedestrian crashes in
      Tennessee.
AB  - Alcohol adversely affects human behavior and judgment, and it is one of the
      contributing factors in traffic crashes. Although a large body of research has
      investigated driving behavior under the influence of the alcohol, to the best of
      our knowledge, no study has investigated the crash characteristics of the
      pedestrians under the influences of the alcohol. Tennessee Police Crash Data from
      2011 to 2016 was used in this study to identify crashes between motor vehicles
      and pedestrians who were walking under the influence of alcohol (WUI). Results
      indicate that the number of fatally injured pedestrians for WUI cases has
      increased since 2011. Alcohol was present in 7% of the pedestrian crashes. Tested
      pedestrians averaged BAC levels of 0.17 g/dL. As pedestrian injury severity
      increased, the share of the WUI crashes increased. WUI contributed in 22% of the
      fatally injured pedestrian and only in 2% of the pedestrian crashes with no
      injury. Comparisons indicate that the WUI crashes had their characteristics,
      which distinguished them from non-WUI crashes. Analysis indicates that 83% of the
      WUI crashes occurred in the nights; moreover, 54%, 69%, and 85% of WUI crashes
      respectively occurred on weekends, mid-block section of the road, and areas with
      no traffic control device. Results of a binary logit regression indicate that
      pedestrian's age, males, posted speed limit, and nighttime crashes had a positive
      association with the WUI crashes. On the other hand, urban context, intersection
      crashes, driver maneuvers (i.e., parking-related, turning, and straight), and
      daylight had a negative association with the WUI crashes. Findings are discussed
      in line with road safety countermeasures.

PMID- 30223083
TI  - Effect of liraglutide on physical performance in type 2 diabetes: Results of a
      randomized, double-blind, controlled trial (LIPER2).
AB  - AIMS: To assess the effect of the GLP-1 analogue liraglutide on measures of
      cardiac function and physical performance in patients with type 2 diabetes (T2D).
      METHODS: In this phase-IV randomized double-blind placebo-controlled parallel
      group clinical trial at a tertiary hospital, T2D patients with HbA1c levels of 7
      10% with oral agents and/or intermediate-/long-acting insulin were allocated
      (computer-generated randomization, ratio 1:1) to either liraglutide 1.8 mg/day or
      a placebo for 6 months. The primary endpoint was maximum oxygen consumption
      (VO2max) during cycle ergometry, while other procedures included a 6-min walk
      test, echocardiography, anthropometry and blood tests. Safety endpoints were also
      monitored, and an intention-to-treat analysis was performed. RESULTS: A total of
      24 patients (15 women) aged 52 (11.7) years, with diabetes duration of 8.7 (5.8)
      years, BMI 34.98 (6.2) kg/m2 and HbA1c 8.2% (0.68%), were randomized to
      liraglutide 1.8 mg daily or placebo. There were no differences in VO2max [17.98
      (4.8) vs. 15.90 (4.96) mL/kg/min; P > 0.10], VE/VCO2 slope [30.18 (4.8) vs. 32
      (4.49)], left ventricular ejection fraction or 6-min walk test [530.7 (86) vs.
      503.9 (84) m] at 6 months. HbA1c was lower (6.7% vs. 7.7%; P =  0.005), with a
      trend towards lower maximum systolic blood pressure during ergometry [171.7
      (24.4) vs. 192.5 (25.6); P = 0.052] in the liraglutide group at the end of the
      study. There were no severe adverse events. CONCLUSION: In this trial,
      liraglutide improved glycaemic control in T2D, but had no significant effects on
      either physical performance or myocardial function.

PMID- 30223085
TI  - Evolutionary considerations on 5-HT2 receptors.
AB  - Serotonin is a neurotransmitter widely conserved from ancient organisms lacking
      nervous systems through man, and its presence precedes the appearance of nervous
      systems on both developmental and evolutionary time scales. Serotonin receptor
      subtypes diversified approximately at the time period during which vertebrates
      diverged from invertebrates. The biological and clinical importance of serotonin
      receptors, may benefit from studies on their evolution. Although potentially
      informative about their pathophysiological functions, reviews on this topic are
      sparse. Several observations support basic functions mediated by serotonin, both
      in periphery and central nervous system. In particular, 5-HT2B receptors have
      been implicated in embryonic development, including cell proliferation, survival,
      and/or differentiation, in either neural crest cell derivatives, myeloid cell
      lineage, or heart embryogenesis. In this review, we collected existing data about
      the genomic association between the RPN2 proteasome subunit gene Psmd1 and the 5
      HT2B receptor gene Htr2b. We discuss about the possibility that, during genome
      duplications, a single copy of this pair of genes has been conserved, suggesting
      a strong selective pressure. Many basic physiological functions in which
      serotonin system is involved could be linked to the early association of these
      two genes in pre-vertebrates. Their evolutionary association highlights the
      possibility that the 5-HT2B receptor gene, Htr2b, is the common ancestor of 5
      HT2A/2B/2C-receptor subfamily. Disentangling these possibilities could bring new
      understanding of the respective importance of these receptors in pathophysiology
      of serotonin.

PMID- 30223084
TI  - Indications for islet or pancreatic transplantation: Statement of the TREPID
      working group on behalf of the Societe francophone du diabete (SFD), Societe
      francaise d'endocrinologie (SFE), Societe francophone de transplantation (SFT)
      and Societe francaise de nephrologie - dialyse - transplantation (SFNDT).
AB  - While either pancreas or pancreatic islet transplantation can restore endogenous
      insulin secretion in patients with diabetes, no beta-cell replacement strategies
      are recommended in the literature. For this reason, the aim of this national
      expert panel statement is to provide information on the different kinds of beta
      cell replacement, their benefit-risk ratios and indications for each type of
      transplantation, according to type of diabetes, its control and association with
      end-stage renal disease. Allotransplantation requires immunosuppression, a risk
      that should be weighed against the risks of poor glycaemic control, diabetic
      lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas
      transplantation is associated with improvement in diabetic micro- and macro
      angiopathy, but has the associated morbidity of major surgery. Islet
      transplantation is a minimally invasive radiological or mini-surgical procedure
      involving infusion of purified islets via the hepatic portal vein, but needs to
      be repeated two or three times to achieve insulin independence and long-term
      functionality. Simultaneous pancreas-kidney and pancreas after kidney
      transplantations should be proposed for kidney recipients with type 1 diabetes
      with no surgical, especially cardiovascular, contraindications. In cases of high
      surgical risk, islet after or simultaneously with kidney transplantation may be
      proposed. Pancreas, or more often islet, transplantation alone is appropriate for
      non-uraemic patients with labile diabetes. Various factors influencing the
      therapeutic strategy are also detailed in this report.

PMID- 30223086
TI  - Uncoupling proteins as a therapeutic target to protect the diabetic heart.
AB  - Myocardial remodeling and dysfunction caused by accelerated oxidative damage is a
      widely reported phenomenon within a diabetic state. Altered myocardial substrate
      preference appears to be the major cause of enhanced oxidative stress-mediated
      cell injury within a diabetic heart. During this process, exacerbated free fatty
      acid flux causes an abnormal increase in mitochondrial membrane potential leading
      to the overproduction of free radical species and subsequent cell damage.
      Uncoupling proteins (UCPs) are expressed within the myocardium and can protect
      against free radical damage by modulating mitochondrial respiration, leading to
      reduced production of reactive oxygen species. Moreover, transgenic animals
      lacking UCPs have been shown to be more susceptible to oxidative damage and
      display reduced cardiac function when compared to wild type animals. This
      suggests that tight regulation of UCPs is necessary for normal cardiac function
      and in the prevention of diabetes-induced oxidative damage. This review aims to
      enhance our understanding of the pathophysiological mechanisms relating to the
      role of UCPs in a diabetic heart, and further discuss known pharmacological
      compounds and hormones that can protect a diabetic heart through the modulation
      of UCPs.

PMID- 30223087
TI  - Catabolic repression in early-diverging anaerobic fungi is partially mediated by
      natural antisense transcripts.
AB  - Early-diverging anaerobic fungi (order: Neocallimastigomycota), lignocelluolytic
      chytrid-like fungi central to fiber degradation in the digestive tracts of large
      herbivores, are attractive sources of cellulases and hemicellulases for
      biotechnology. Enzyme expression is tightly regulated and coordinated through
      mechanisms that remain unelucidated to optimize hydrolytic efficiency. Our
      analysis of anaerobic fungal transcriptomes reveals hundreds of cis-natural
      antisense transcripts (cis-NATs), which we hypothesize play an integral role in
      this regulation. Through integrated genomic and transcriptomic sequencing on a
      range of catabolic substrates, we validate these NATs in three species
      (Anaeromyces robustus, Neocallimasix californiae, and Piromyces finnis), and
      analyze their expression patterns and prevalence to gain insight into their
      function. NAT function was diverse and conserved across the three fungal genomes
      studied, with 10% of all metabolic process NATs associated with lignocellulose
      hydrolysis. Despite these similarities, however, only eleven gene targets were
      conserved orthologs. Several NATs were dynamically regulated by lignocellulosic
      substrates while their gene targets were unregulated. This observation is
      consistent with a hypothesized, but untested, regulatory mechanism where selected
      genes are exclusively regulated at the transcriptional/post-transcriptional level
      by NATs. However, only genes with high NAT relative expression levels displayed
      this phenomenon, suggesting a selection mechanism that favors larger dynamic
      ranges for more precise control of gene expression. In addition to this mode, we
      observed two other possible regulatory fates: canonical transcriptional
      regulation with no NAT response, and positive co-regulation of target mRNA and
      cognate NAT, which we hypothesize is a fine-tuning strategy to locally negate
      control outputs from global regulators. Our work reveals the complex
      contributions of antisense RNA to the catabolic response in anaerobic fungi,
      highlighting its importance in understanding lignocellulolytic activity for
      bioenergy applications. More importantly, the relative expression of NAT to
      target may form a critical determinant of transcriptional vs post-transcriptional
      (NAT) control of gene expression in primitive anaerobic fungi.

PMID- 30223088
TI  - Non-O157 Shiga toxin-producing Escherichia coli-A poorly appreciated enteric
      pathogen: Systematic review.
AB  - Non-O157 strains of Shiga toxin-producing Escherichia coli (STEC) are more common
      causes of acute diarrhea than the better-known O157 strains and have the
      potential for large outbreaks. This systematic review of the literature
      identified 129 serogroups as well as 262 different O and H antigen combinations
      of STEC in cases of epidemic and sporadic disease worldwide. Excluding the
      results from a single large outbreak of STEC O104:H4 in Germany and France in
      2011, the reported frequency of dysenteric illness in patients was 26% (119 of
      464) for epidemic disease and 25% (646 of 2588) for sporadic cases. Hemolytic
      uremic syndrome was identified in 14% of epidemic disease cases and 9% of
      sporadic illness cases. With the increasing use of PCR-based diagnostics, STEC
      strain identification may not be possible. Rapid diagnostics are needed for STEC
      infections to aid the clinician while allowing epidemiologists the opportunity to
      identify outbreaks and to trace the source of infection.

PMID- 30223089
TI  - Effect of narcotic prescription limiting legislation on opioid utilization
      following lumbar spine surgery.
AB  - BACKGROUND CONTEXT: Prescription opioid abuse is a public health emergency.
      Opioid prescriptions for spine patients account for a large proportion of use.
      Some states have implemented statutory limits on prescribers, however it remains
      unclear whether such laws are effective. PURPOSE: This investigation compares
      opioid prescription patterns for patients undergoing lumbar spine surgery before
      and after the passage of statewide narcotic-limiting legislation in Rhode Island.
      STUDY DESIGN/SETTING: Retrospective review of prospectively-collected medical and
      pharmacologic data. PATIENT SAMPLE: Two patient cohorts (pre-law January 1, 2016
      June 31, 2016 and post-law June 1, 2017-December 31, 2017) that included all
      patients undergoing selected lumbar spine surgeries (lumbar discectomy, lumbar
      decompression without fusion, and posterior lumbar fusion). METHODS: Demographic
      and surgical variables were collected from the patient's medical charts, and
      information on controlled substances was collected from the state prescription
      drug monitoring program database. Variables collected included the number of
      pills and total morphine milligram equivalents (MMEs) of the first prescription,
      number of prescriptions filled within 30 days of surgery, total MMEs filled in
      the 30-day postoperative period, and total MMEs filled from 30 to 90 days after
      surgery. For comparison of continuous variables, t test or Mann-Whitney U test
      were used as appropriate. Chi-squared analysis was utilized for comparison of
      categorical variables. Independent risk factors for prolonged postoperative
      opioid use were evaluated using logistic regression. RESULTS: There were no
      significant differences between pre-law (n = 241) and post-law (n = 311) cohorts
      in terms of age, sex, preoperative opioid use, or preoperative anxiolytic use (p
      > .05). A greater than 50% decline was observed among all patients from the pre
      law to the post-law period in terms of the number of pills (51.61 vs 23.60 pills,
      p < .001) and MMEs (525.56 vs 218.77 MMEs, p < .001) provided in the first
      postoperative opioid prescription. The mean total MMEs provided in the first 30
      days decreased significantly (891.26 vs 628.63 MMEs, p < .001) despite an
      increase in the average number of opioid prescriptions filled (1.75 vs 2.04
      prescriptions, p = .002) during this time. There was no significant difference in
      mean MMEs filled from 30 to 90 days. Upon subgroup analysis, there was a
      statistically significant decline in both the mean first prescription and total
      30-day MMEs regardless of preoperative opioid status (all p < .05) or specific
      procedure performed (all p < .05). Preoperative opioid use was strongly
      associated with prolonged postoperative opioid requirements throughout the study
      period (OR 4.71, 95% CI 3.11-7.13, p < .001). There were no significant
      differences between cohorts in terms of emergency department (ED) visits or
      unplanned hospital readmissions at 30 and 90 days following surgery (all p >
      .05). CONCLUSIONS: The institution of mandatory statewide opioid prescription
      limits has resulted in a significant reduction in initial and 30-day opioid
      prescriptions following lumbar spine surgery. Decreased opioid utilization was
      observed in all patients, regardless of preoperative opioid tolerance or
      procedure performed. No significant change in postoperative ED visits or
      unplanned hospital readmissions was seen following implementation of the
      legislation. This investigation provides preliminary evidence that narcotic
      limiting legislation may be effective in decreasing opioid prescriptions after
      lumbar spine surgery for both opioid-naive and opioid-tolerant patients.

PMID- 30223090
TI  - Predicting and understanding collagen remodeling in human native heart valves
      during early development.
AB  - The hemodynamic functionality of heart valves strongly depends on the
      distribution of collagen fibers, which are their main load-bearing constituents.
      It is known that collagen networks remodel in response to mechanical stimuli.
      Yet, the complex interplay between external load and collagen remodeling is
      poorly understood. In this study, we adopted a computational approach to simulate
      collagen remodeling occurring in native fetal and pediatric heart valves. The
      computational model accounted for several biological phenomena: cellular
      (re)orientation in response to both mechanical stimuli and topographical cues
      provided by collagen fibers; collagen deposition and traction forces along the
      main cellular direction; collagen degradation decreasing with stretch; and cell
      mediated collagen prestretch. Importantly, the computational results were well in
      agreement with previous experimental data for all simulated heart valves.
      Simulations performed by varying some of the computational parameters suggest
      that cellular forces and (re)orientation in response to mechanical stimuli may be
      fundamental mechanisms for the emergence of the circumferential collagen
      alignment usually observed in native heart valves. On the other hand, the
      tendency of cells to coalign with collagen fibers is essential to maintain and
      reinforce that circumferential alignment during development. STATEMENT OF
      SIGNIFICANCE: The hemodynamic functionality of heart valves is strongly
      influenced by the alignment of load-bearing collagen fibers. Currently, the
      mechanisms that are responsible for the development of the circumferential
      collagen alignment in native heart valves are not fully understood. In the
      present study, cell-mediated remodeling of native human heart valves during early
      development was computationally simulated to understand the impact of individual
      mechanisms on collagen alignment. Our simulations successfully predicted the
      degree of collagen alignment observed in native fetal and pediatric semilunar
      valves. The computational results suggest that the circumferential collagen
      alignment arises from cell traction and cellular (re)orientation in response to
      mechanical stimuli, and with increasing age is reinforced by the tendency of
      cells to co-align with pre-existing collagen fibers.

PMID- 30223091
TI  - Polylysine-modified polyethylenimine polymer can generate genetically engineered
      mesenchymal stem cells for combinational suicidal gene therapy in glioblastoma.
AB  - Glioblastoma remains the most resistant malignant brain tumor owing to the lack
      of an efficient delivery system for therapeutic genes or drugs, especially in
      outgrowing tumor islands. Cell-based delivery systems such as mesenchymal stem
      cells (MSCs) are a potential candidate in this regard. Conventionally, MSCs have
      been genetically modified for cancer therapy by using viral vectors that can
      illicit oncogenicity and limit their use in clinical trials. In this study, we
      have used nonviral agents such as the polylysine-modified polyethylenimine (PEI
      PLL) copolymer to generate genetically engineered MSCs with suicidal genes,
      namely, HSV-TK and TRAIL. Our results demonstrated that an intratumoral injection
      of polymer-double-transfected MSCs along with prodrug ganciclovir injections can
      induce a significant synergistic therapeutic response both in vitro and in vivo
      compared to single plasmid transfections or untransfected MSCs. The proliferation
      marker Ki67 and the angiogenesis marker VEGF were also significantly reduced in
      treatment groups, whereas the TUNEL assay demonstrated that apoptosis is
      significantly increased after treatment. Our findings suggest that the PEI-PLL
      copolymer can successfully modify MSCs with therapeutic genes and can produce a
      pronounced impact during glioblastoma therapy. This study proposes a potential
      nonviral approach to develop a cell-based therapy for the treatment of glioma.
      STATEMENT OF SIGNIFICANCE: In this study, we have used a polylysine-modified
      polyethylenimine polymer (PEI-PLL) copolymer, a non viral transfection agent, for
      gene delivery in mesenchymal stem cells. These PEI-PLL-transfected mesenchymal
      stem cells with HSV-TK and TRAIL genes have the potential to treat glioma both in
      vitro and in vivo. This combinational therapy through PEI-PLL-transfected
      mesenchymal stem cells can provide cost-effective, low immunogenic, and tumor
      targeted delivery of suicideal genes (HSV-TK and TRAIL) for promising
      glioblastoma treatment.

PMID- 30223092
TI  - Platelet-mimicking nanoparticles co-loaded with W18O49 and metformin alleviate
      tumor hypoxia for enhanced photodynamic therapy and photothermal therapy.
AB  - W18O49-mediated photodynamic therapy (PDT) and photothermal therapy (PTT) are
      limited by the easily oxidized property and tumor hypoxia. Here, we report the
      development of platelet membranes as nanocarriers to co-load W18O49 nanoparticles
      (NPs) and metformin (PM-W18O49-Met NPs). Platelet membranes can protect W18O49
      from oxidation and immune evasion, and increase the accumulation of W18O49 in
      tumor sites via the passive EPR effect and active adhesion between platelets and
      cancer cells. The introduction of metformin (Met), a typical anti-diabetic drug,
      can alleviate the tumor hypoxia through reducing oxygen consumption. As a result,
      ROS and heat generation are both greatly increased, as revealed by ROS/hypoxia
      imaging in vitro, IR thermal imaging in vivo and PET imaging in vivo. PM-W18O49
      Met NPs show the improved therapeutic effects with greatly inhibited tumor growth
      and induced tumor cell apoptosis. Therefore, our work provides a novel strategy
      for simultaneous enhanced PDT and PTT, which is promising in bioapplication.
      STATEMENTE OF SIGNIFICANCE: W18O49-mediated photodynamic therapy and photothermal
      therapy are limited by the poor delivery of nanoparticles to tumors, the easily
      oxidized property, and tumor hypoxia environment, which will induce tumor
      treatment failure. Herein, we report the development of platelet membranes as
      nanocarriers to co-load W18O49 nanoparticles and metformin (PM-W18O49-Met NPs).
      Platelet membranes can protect W18O49 from oxidation and immune evasion, and
      increase the accumulation of W18O49 in tumor sites via the passive EPR effect and
      active adhesion. Metformin can alleviate the tumor hypoxia through reducing
      oxygen consumption. Hence, ROS and heat generation are both greatly increased. PM
      W18O49-Met NPs show the improved therapeutic effects with greatly inhibited tumor
      growth and induced apoptosis. Therefore, our work provides a novel strategy in
      bioapplication.

PMID- 30223093
TI  - Design of DNA-based innovative computing system of digital comparison.
AB  - Despite great potential and extensive interest in developing biomolecule-based
      computing, the development of even basic molecular logic gates is still in its
      infancy. Digital comparator (DC) is the basic unit in traditional electronic
      computers, but it is difficult to construct a system for achieving large-scale
      integration. Here, we construct, for the first time, a novel logic computing
      system of DCs that can compare whether two or more numbers are equal. Our
      approach is by taking advantage of facile preparation and unique properties of
      graphene oxide and DNA. The DC system reported in this work is developed by the
      DNA hybridization and effective combination of GO and single-stranded DNA, which
      is regarded as the reacting platform. On the basis of this platform and reaction
      principle, we have developed 2-inputs, 3-inputs, and 4-inputs DCs to realize the
      comparison of two or more binary numbers. We predict that such a state-of-the-art
      logic system enables its functionality with large-scale input signals, providing
      a new direction toward prototypical DNA-based logic operations and promoting the
      development of advanced logic computing. STATEMENT OF SIGNIFICANCE: The
      overarching objective of this paper is to explore the construction of a novel DNA
      computing system of digital comparator driven by the interaction of DNA and
      graphene oxide (GO). GO can efficient bind the dye-labeled, single-stranded DNA
      probe and then quench its fluorescence. In the case of the target appearing,
      specific binding between the single-stranded probe and its target occurs,
      changing the conformation and relationship with GO, then restoring the
      fluorescence of the dye. We have developed the 2-inputs, 3-inputs, and 4-inputs
      digital comparator circuits, which are expected to realize the comparison of
      large-scale input signals and can avoid the problems of design complexity and
      manufacturing cost of integrated circuits in traditional computing.

PMID- 30223094
TI  - Stiffness memory nanohybrid scaffolds generated by indirect 3D printing for
      biologically responsive soft implants.
AB  - Cell and tissue stiffness is an important biomechanical signalling parameter for
      dynamic biological processes; responsive polymeric materials conferring
      responsive functionality are therefore appealing for in vivo implants. We have
      developed thermoresponsive poly(urea-urethane) nanohybrid scaffolds with
      'stiffness memory' through a versatile 3D printing-guided thermally induced phase
      separation (3D-TIPS) technique. 3D-TIPS, a combination of 3D printing with phase
      separation, allows uniform phase-separation and phase transition of the polymer
      solution at a large interface of network within the printed sacrificial preform,
      leading to the creation of full-scale scaffolds with bespoke anatomical complex
      geometry. A wide range of hyperelastic mechanical properties of the soft
      elastomer scaffolds with interconnected pores at multi-scale, controlled porosity
      and crystallinity have been manufactured, not previously achievable via direct
      printing techniques or phase-separation alone. Semi-crystalline polymeric reverse
      self-assembly to a ground-stated quasi-random nanophase structure, throughout a
      hierarchical structure of internal pores, contributes to gradual stiffness
      relaxation during in vitro cell culture with minimal changes to shape. This
      'stiffness memory' provides initial mechanical support to surrounding tissues
      before gradually softening to a better mechanical match, raising hopes for
      personalized and biologically responsive soft tissue implants which promote human
      fibroblast cells growth as model and potential scaffold tissue integration.
      STATEMENT OF SIGNIFICANCE: Biological processes are dynamic in nature, however
      current medical implants are often stronger and stiffer than the surrounding
      tissue, with little adaptability in response to biological and physical stimuli.
      This work has contributed to the development of a range of thermoresponsive
      nanohybrid elastomer scaffolds, with tuneable stiffness and hierarchically
      interconnected porous structure, manufactured by a versatile indirect 3D printing
      technique. For the first time, stiffness memory of the scaffold was observed to
      be driven by phase transition and a reverse self-assembly from a semicrystalline
      phase to a quasi-random nanostructured rubber phase. Early insight into cell
      response during the stiffness relaxation of the scaffolds in vitro holds promise
      for personalized biologically responsive soft implants.

PMID- 30223095
TI  - Molecular dynamics simulations of adsorption and desorption of bone morphogenetic
      protein-2 on textured hydroxyapatite surfaces.
AB  - Interactions between bone morphogenetic protein-2 (BMP-2) and biomaterial
      surfaces are of great significance in the fields of regenerative medicine and
      bone tissue engineering. In this work, the adsorption and desorption behaviors of
      BMP-2 on a series of nano-textured hydroxyapatite (HAP) surfaces were
      systematically investigated by combined molecular dynamic (MD) simulations and
      steered molecular dynamic (SMD) simulations. The textured HAP surfaces exhibited
      nanostructured topographies and played a critical role in the mediation of
      dynamic behaviors of BMP-2. Compared to the HAP-flat model, the HAP-1:1 group
      (means ridge vs groove = 1:1) showed the excellent ability to capture BMP-2, less
      conformation change of BMP-2 molecule, and high cysteine-knot stability during
      the adsorption and desorption processes. These findings suggest that nano
      textured HAP surfaces are more capable of loading BMP-2 molecules, and most
      importantly, they can help maintain a higher biological activity of BMP-2 cargos.
      In the present study, for the first time, we have deeply clarified the adsorption
      and desorption dynamics of BMP-2 on various nano-textured HAP surfaces at the
      atomic level, which can provide significant guidelines for the future design of
      BMP-2-based tissue engineering implants/scaffolds. STATEMENT OF SIGNIFICANCE: By
      using combined molecular dynamic (MD) simulations and steered molecular dynamic
      (SMD) simulations, the adsorption and desorption dynamics of bone morphogenetic
      protein-2 (BMP-2) dimer on a series of nano-textured hydroxyapatite (HAP)
      surfaces at the atomic level were presented in details for the first time. We
      have proved that the HAP-1:1 model (means ridge vs groove = 1:1) possessed
      excellent ability to capture BMP-2, less conformation change, and high cysteine
      knot stability. As a result, the nano-textured topography of HAP-1:1 could
      maintain a relatively high biological activity of BMP-2 cargos. This work could
      provide theoretical guidelines for the design of BMP-2-based implants/scaffolds
      for bone tissue engineering.

PMID- 30223097
TI  - Differential consequences of neurokinin receptor 1 and 2 antagonists in
      metastatic breast carcinoma cells; Effects independent of Substance P.
AB  - INTRODUCTION: The biological action of Substance P (SP) is mediated mainly by NK
      1 receptors (NK1R) followed by NK2 receptors (NK2R). Aberrant expression of NK1R
      and NK2R has been identified in various carcinomas. The role of Substance P and
      its receptors, especially NK2R in cancer progression is not entirely known and
      there are conflicting results in the literature demonstrating the need for
      further investigation. In the current study, we examined the effects of SP and
      antagonists selective for the NK1R and NK2R in breast carcinoma cells metastasize
      to vital organs. METHODS: The effects of highly potent and selective non-peptide
      mouse NK1R and NK2R antagonists RP 67,580 and GR 159897, respectively, as well as
      SP and SP methyl ester, on both metastatic (4THM, 4TBM, 4TLM, 4T1) and non
      metastatic (67NR) breast cancer cells were determined. RESULTS: NK1R and NK2R
      were over expressed in metastatic breast cells compared to non-metastatic cells.
      The NK1R antagonist at a 30 MUM dose inhibited cell growth and induced cell death
      in metastatic cells while enhancing phosphorylation of Akt, the latter response
      not observed in the non-metastatic 67NR cells. Blocking the action of SP at the
      NK2R (30 MUM antagonist) suppressed cellular proliferation in all the cell lines
      examined, with a response less prominent than that of the NK1R antagonist.
      Differently, the NK2R antagonist increased phosphorylation of p38 and enhanced
      MIP-2 secretion. SP and the SP methyl ester neither altered cell proliferation
      nor the effects of NK1R and NK2R antagonists in the metastatic cell lines.
      CONCLUSIONS: Increased sensitivity of metastatic breast carcinoma cells to NK1R
      and NK2R antagonists suggest potential therapeutic value of antagonists in
      metastatic disease. NK1R and NK2R in metastatic breast carcinoma cells react
      differently to agonists and antagonists. These findings together with previously
      published data demonstrate that differential consequences of receptor antagonists
      and SP may inhibit breast cancer growth and metastasis.

PMID- 30223096
TI  - Therapeutic effects of honokiol on motor impairment in hemiparkinsonian mice are
      associated with reversing neurodegeneration and targeting PPARgamma regulation.
AB  - Parkinson's disease (PD) is a profound neurodegenerative disorder with gradual
      loss of dopamine nigrostriatal neurons linked to serious behavioral symptoms.
      While the current treatment strategies present limitations on halting the
      progression of PD, this study aimed to investigate the therapeutic potential of
      honokiol, as a partial peroxisome proliferator-activated receptor-gamma
      (PPARgamma) mimic, on the proceeding behavioral and biochemical alterations in
      hemiparkinsonian mice. Results showed that unilateral striatal 6-hydroxydopamine
      (6-OHDA)-lesioned mice exhibited motor impairment, reflecting the contralateral
      rotation induced by apomorphine at 1-3 weeks post-lesion. Subchronic honokiol
      administration for 1-2 weeks, beginning 7 days after 6-OHDA-lesion, dose
      dependently ameliorated motor dysfunction in hemiparkinsonian mice. Recovery of
      motor function was correlated with reversal of nigrostriatal dopaminergic
      neuronal loss, accompanied by higher tyrosine hydroxylase (TH) density, dopamine
      transporter (DAT) expression and vesicular monoamine transporter-2 (VMAT2)
      levels. Furthermore, honokiol attenuated oxidative stress and reactive astrocyte
      induction via decreasing NADPH-oxidase and glial fibrillary acidic protein (GFAP)
      expressions in 6-OHDA-lesioned striatum. The reversal effects of honokiol on
      behavioral impairment and striatal PPARgamma expression were impeded by PPARgamma
      antagonist GW9662. Notably, subchronic honokiol treatment extended the lifespan
      of these hemiparkinsonian mice. The present findings demonstrate the therapeutic
      activities of honokiol in ameliorating motor impairment and progressive
      dopaminergic damage that could be associated with regulating PPARgamma signaling.
      Therefore, honokiol may potentially exert as a novel therapeutic candidate
      through PPARgamma activation for management of motor symptoms and progressive
      neurodegeneration in PD.

PMID- 30223098
TI  - microRNA-300/NAMPT regulates inflammatory responses through activation of
      AMPK/mTOR signaling pathway in neonatal sepsis.
AB  - AIM: Rapid and accurate diagnosis of neonatal sepsis (NS) is highly warranted
      because of high associated morbidity and mortality. The study aims to evaluate
      the effects of miR-300 on inflammatory responses in a septic neonate mouse model.
      METHODS: A septic mouse model was established by intraperitoneal (i.p.) cecal
      slurry (CS) injection in order to validate the effect of miR-300 on the
      inflammatory response in endothelial cells. Bioinformatics tools and luciferase
      activity were employed to detect the target of miR-300. Serum inflammatory
      factors were determined by ELISA assay. RT-qPCR and western blot analysis were
      used to determine the gene expressions. Flow cytometry was employed to evaluate
      cell apoptosis. RESULTS: Gain- and loss-of-function studies revealed that miR-300
      overexpression augmented autophagy, inhibited cell apoptosis, enhanced cell cycle
      entry in endothelial cells, and decreased inflammatory response through the
      regulation of pro- and anti-apoptotic factors in endothelial cells. The effect of
      miR-300on endothelial cells was upregulated after nicotinamide
      phosphoribosyltransferase (NAMPT) silencing and AMPK/mTOR signaling pathway
      activation, indicating that miR-300 influences sepsis via suppressing NAMPT and
      triggering the AMPK/mTOR signaling pathway. CONCLUSIONS: Our study provides
      evidence indicating that overexpressedmiR-300 enhances autophagy by targeting
      NAMPT through activation of the AMPK/mTOR signaling pathway in septic mouse
      models, indicating it may serve as a potential therapeutic target for sepsis.

PMID- 30223099
TI  - Possible therapeutic potential of berberine in the treatment of STZ plus HFD
      induced diabetic osteoporosis.
AB  - Diabetic osteoporosis is a complication of diabetes mellitus, and can result in
      an increased incidence of bone fractures and a delay in fracture healing.
      Berberine is one of the most widely distributed isoquinoline alkaloid in plants
      and possesses antioxidant properties. These properties can reduce the high
      glucose mediated in the dysfunction of human bone marrow stem cells. Therefore,
      the present study was designed to investigate the apparent beneficial effect of
      berberine on bone characteristics in streptozotocin plus HFD-induced diabetic
      rats. Rats were selected at random and divided into four groups: (A) control
      group (CG) (n = 10); (B) diabetic group (DG) (n = 10); (C) diabetic group with 50
      mg kg-1day-1 of berberine (Brb-50) (n = 10); and (D) diabetic group with 100 mg
      kg-1day-1 of berberine (Brb-100) (n = 10). After 12 weeks of being treated with
      berberine, the femora from all rats were assessed and other blood biochemistries
      evaluated. Berberine at 50 mg/kg showed little effect and significance on
      diabetic osteopenia, while berberine at 100 mg/kg was significantly increased in
      diabetic rats. The same group also displayed a significantly decreased serum
      osteocalcin and serum alkaline phosphatase activity in diabetic rats. The
      impaired micro-architecture of the femurs in diabetic rats could partially be
      prevented by berberine with 100 mg/kg. In addition, berberine could to an extent
      restore the decreased bone formation and reabsorption of the femurs in diabetic
      rats through the histomorphometric analysis. Berberine could not only
      significantly lower the oxidative level of DNA damage, but also up-regulate the
      activity of serum antioxidants. According to our investigations and discoveries,
      we have found, that berberine may be a potential drug for controlling bone loss
      in diabetic osteoporosis.

PMID- 30223100
TI  - Genome-wide methylation analysis identifies novel prognostic methylation markers
      in colon adenocarcinoma.
AB  - Previous studies have indicated that abnormal methylation is a critical and early
      event in the pathogenesis of most types of human cancer, which contributes to
      tumorigenesis. However, there has been little focus on the potential of DNA
      methylation patterns as predictive markers for the prognosis of colon
      adenocarcinoma (COAD). In the present study, a genome-wide comparative analysis
      of DNA methylation profiles was performed between 315 COAD samples and 38 matched
      tumor-adjacent normal tissue samples. A total of 675 differentially methylated
      regions (DMRs) associated with 630 genes were identified, including 654
      hypermethylated regions (UMRs) and 21 hypomethylated regions, which were capable
      of distinguishing COAD samples from non-malignant tissue samples. Although most
      of the DMRs appeared to be located within the gene body or promoter regions, UMRs
      were mostly located within CpG islands. Functional analysis suggested that genes
      associated with DMRs were enriched in many of the core cancer-signaling pathways
      known to be important in COAD biology. A survival analysis was also performed,
      which identified 7 DMRs as potential candidate markers with the ability to
      classify patients into high and low-risk groups with significantly different
      overall survival. The present study provides a better understanding of the
      molecular mechanisms underlying COAD, and demonstrates the utility of aberrant
      DNA methylation in the prognosis of COAD.

PMID- 30223101
TI  - Copper (II)-ploy-L-histidine functionalized multi walled carbon nanotubes as
      efficient mimetic enzyme for sensitive electrochemical detection of salvianic
      acid A.
AB  - In this work, carboxylated multi walled carbon nanotubes (CMWCNTs) were firstly
      prepared and functionalized with poly-L-histidine (PLH), which were then chelated
      with copper (II) ions to from the nanocomposites of Cu(II)-PLH-CMWCNTs. The
      nanocomposites could be exploited as an efficient mimic enzyme for sensitive
      electrochemical detection of salvianic acid A (SAA). Cu(II)-PLH-CMWCNTs owned
      good charge transfer property and excellent synergetic catalytic effect between
      the overoxidized imidazole groups and the copper redox-active units. Therefore,
      highly sensitive electrochemical response to SAA was achieved under optimum
      experimental conditions. A good linear relationship between differential pulse
      voltammetry (DPV) peak current and the SAA concentration was established in the
      range of 0.4-1000 MUM. A low detection limit of 0.037 MUM and a sensitivity of
      0.27 MUA MUM-1 cm-2 were achieved. The developed biosensor also had advantages of
      good repeatability, stability and high selectivity, thus, it was successfully
      applied to the determination of SAA in real samples with satisfactory results,
      which may have great potential for further exploitation of electroanalysis
      applications.

PMID- 30223102
TI  - Layer-by-layer electrochemical biosensors configuring xanthine oxidase and carbon
      nanotubes/graphene complexes for hypoxanthine and uric acid in human serum
      solutions.
AB  - A selective biosensing platform for the determination of hypoxanthine (Hx) and
      uric acid (UA) concentrations in both buffer and human serum sample solutions was
      developed. The biosensor features the layer-by-layer (LbL) self-assembly of
      negatively charged xanthine oxidase (XOD) and positively charged
      poly(diallyldimethyl ammonium chloride) (PDDA) wrapped oxidized multi-walled
      carbon nanotubes and graphene (CNTs-G) complexes (PDDA-CNTs-G) on screen printed
      carbon electrode (SPCE) surfaces. Catalytic responses of the XOD modified
      biosensor with the chosen optimum number of layers for LbL assembly on SPCE
      towards Hx in buffer solutions were first investigated using both cyclic and
      square wave voltammetries. The peak current at around 0.08 V (vs. Ag/AgCl)
      associated with the production of UA increased as a function of the Hx
      concentration due to the surface selective catalytic reaction of XOD and Hx. A
      linear dynamic range of 5-50 uM Hx with a detection limit of 4.40 uM was obtained
      and the sensor was further applied to the analysis of Hx in normal human serum
      solutions in addition to myocardial infarction (MI) patient serum sample
      solutions from a local hospital. Since untreated serum solutions contain a
      certain amount of UA, a XOD free SPCE biosensor consisted of only PDDA-CNTs-G was
      also employed to evaluate the native concentration of UA in the serum and further
      assist the determination of Hx concentration when using the developed LbL
      biosensor. Our sensing results for the real biological fluidic solutions were
      finally validated by comparing to those using liquid chromatography-mass
      spectrometry(LC-MS).

PMID- 30223103
TI  - Recent advances in microfluidic chip integrated electronic biosensors for
      multiplexed detection.
AB  - Utilizing biosensors for multiplexed detection can greatly increase analysis
      throughput and thus, the amount of information obtained in a single assay. The
      microfluidic chip, a type of micro-total analysis system (uTAS), has provided a
      necessary platform for portable and high-throughput biosensors. Biosensors and
      microfluidic chips are powerful individually, and their super combination is very
      meaningful for analytical especially for biological applications. In this paper,
      every kind of microfluidic-chip-integrated electronic biosensors including some
      emerging technologies for simultaneous detection of multiple analytes are
      reviewed. Different ways to reduce or avoid cross-talking and more efforts to
      achieve lab on chip multisensors were also introduced to help readers form a
      general idea of current developments in different angles.

PMID- 30223104
TI  - Like an empowering micro-home: A qualitative study of women's experience of
      giving birth in water.
AB  - OBJECTIVE: To describe women's experiences and perceptions of giving birth in
      water. DESIGN: A qualitative study with in-depth interviews three to five months
      after the birth. A content analysis of the interviews was made. SETTING: One city
      located hospital in Stockholm, offering waterbirth to low risk women.
      PARTICIPANTS: 20 women, 12 primiparas and 8 multiparas, aged 27-39. MEASUREMENTS
      AND FINDINGS: The overall theme emerging from the analysis was, "Like an
      empowering micro-home", which describes the effect of being strengthened, enabled
      and authorized in the birth process. Three categories were found: "Synergy
      between body and mind", "Privacy and discretion", and "Natural and pleasant". KEY
      CONCLUSIONS: The immersion in warm water provided the women with conditions that
      helped them to cope and feel confident during labour and birth. The homelike and
      limited space of a bathtub helped give a relaxed feeling of privacy, safety,
      control and focus for the women. IMPLICATIONS FOR PRACTICE: This study
      contributes to a deeper understanding of what waterbirth offers to women. For
      some women, waterbirth may be a way to accomplish an empowering and positive
      birth experience, and could work as a tool that preserves the normality of, and
      increases self-efficacy in, childbirth.

PMID- 30223106
TI  - The role of structured Antenatal Risk Management (sARM) on experiences with
      antenatal care by vulnerable clients.
AB  - INTRODUCTION: Vulnerable clients (i.e. clients reporting psychopathology,
      psychosocial problems, or substance use, and/or features of deprivation)
      represent a challenge in perinatal care, both in term of care process and
      outcome. Adhering to a structured care process (i.e. structured Antenatal Risk
      Management [sARM]) has shown to benefit professionals in supporting vulnerable
      clients, but its effect on client experiences is yet to be determined. As better
      processes are assumed to benefit outcome, we investigated the relationship
      between vulnerable clients' experiences with antenatal care in perinatal units
      adhering to differing degrees of sARM. METHODS: We combined data from two
      sources: on the client level antenatal collected survey data from which
      vulnerability status (Mind2Care instrument) and client experiences (ReproQ
      questionnaire) were derived, and on the unit level interview data from healthcare
      providers from which the unit degree of sARM was ascertained. RESULTS: A total of
      N = 1.176 clients from N = 38 units were included in the study. Vulnerable
      clients with psychosocial problems reported more negative experiences than non
      vulnerable clients. In high sARM units, vulnerable clients, regardless of type of
      problems, reported more negative experiences than non-vulnerable clients. In
      multiple regression analysis this effect disappeared and only vulnerability
      defined as psychosocial problems remained predictive for negative experiences.
      CONCLUSIONS: Vulnerable clients, specifically those with psychosocial problems,
      present a challenge in perinatal healthcare. Negative appraisal of care might be
      an unavoidable drawback of adhering to sARM. It also stresses the need for
      improving caregiver-client expectations and system side improvements.

PMID- 30223105
TI  - Fathers for the first time: Validation of a questionnaire to asses father
      experiences of first childbirth in Latin America.
AB  - : The active incorporation of men in the process of childbirth is an increasingly
      common practice internationally. However, there are no validated instruments for
      Latin America. OBJECTIVE: To validate an instrument to assess new fathers'
      experiences during childbirth in Latin America. DESIGN: Prospective validation
      study. SETTING: Talcahuano, Chile. POPULATION: Fathers who participated in the
      birth of their first child (n = 220) between September 2015 to May 2016, in a
      public hospital in Chile. METHODS: The Swedish questionnaire "First Time Fathers
      Questionnaire" was used. As a first step, the questionnaire was translated to
      Spanish, followed by expert judgment of such translation and validation. For
      content validity, a descriptive analysis of the expert judgment and combined
      Kappa evaluation was performed. Construct validity with Exploratory Factor
      Analysis was done. Reliability based on internal consistency, was tested using
      Cronbach's Alpha. Criteria validity was tested with Pearson correlation and
      Student t-test, and logistic regression. MAIN OUTCOME MEASURES: Questionnaire in
      Spanish with adequate evidence of reliability and validity. RESULTS: Two
      components were identified: "Support from the Health System" and "Father Worry",
      with 19 items and adequate internal reliability (0.84 and 0.79 respectively).
      There is a statistically significant inverse correlation between "Father Worry"
      and "Support from the Health System". There is a statistically significant
      association between "Father Worry" and the type of delivery, being higher in
      Caesarean sections. There is a statistically significant association between
      "Support of the Health System" and preparation for childbirth being higher in
      those who were prepared. CONCLUSIONS: This study provides a validated instrument
      to assess the experience of fathers who participate in the birth of their first
      child in Latin America. IMPLICATIONS FOR PRACTICE: The evaluation of the paternal
      experience during birth contributes to the knowledge of the male's emotional
      processes involved in this event. Midwifery is in a key position to promote a
      transcendent parental experience.

PMID- 30223107
TI  - Formation of odorous and hazardous by-products from the chlorination of amino
      acids.
AB  - The formation of odorous aldehydes and N-chloraldimines, and also nitriles, which
      are potentially hazardous to human health, was investigated in studies of the
      chlorination of amino acids (AAs) in both operational drinking water treatment
      plants and laboratory-based experiments. In the drinking water treatment plants
      studied, the concentration of total free AAs did not significantly change after
      treatment, even though good removal of DOC was observed. However, free AAs still
      contributed less than 3% of total nitrogen in the treated drinking waters, and no
      aldehydes, N-chloraldimines or nitriles of interest were detected in the treated
      waters, presumably due to the low concentrations of the precursor AAs in these
      water samples. Laboratory formation potential experiments showed that carboxylic
      acids can form from the degradation of aldehydes and nitriles. Volatile
      carboxylic acids could result in odour issues and some carboxylic acids may be of
      potential health concern. Therefore, carboxylic acids should also be considered
      as potential by-products of interest in distribution systems with long contact
      times of >= 7days. A higher proportion of nitrile formation, and promotion of
      carboxylic acid formation, was observed when the chlorine to AA ratio was greater
      than 4 compared to when this ratio was 2.8, indicating that the Cl:AA ratio is an
      important factor in DBP formation pathways. This suggests that results from
      laboratory formation studies undertaken at these low Cl:AA ratios cannot be
      directly applied to 'real' water systems, which typically have Cl:AA ratios that
      are orders of magnitude higher than 4. Laboratory formation potential experiments
      also showed that the short-term rate of formation of aldehydes and N
      chloraldimines was reduced in the presence of ammonia, although formation over
      longer timescales (e.g. 7 days) was not significantly different between
      chlorination and chloramination experiments. Therefore, the use of chloramination
      instead of chlorination does not appear to reduce the formation of these by
      products from AAs.

PMID- 30223108
TI  - Glyphosate dispersion, degradation, and aquifer contamination in vineyards and
      wheat fields in the Po Valley, Italy.
AB  - Biodegradation of glyphosate (GLP) and its metabolite aminomethylphosphonic acid
      (AMPA) was numerically assessed for a vineyard and a wheat field in the Po
      Valley, Italy. Calculation of the Hazard Quotient suggested that GLP and AMPA can
      pose a risk of aquifer contamination in the top 1.5 m depth within 50 years of
      GLP use. Numerical results relative to soil GLP and AMPA concentrations, and GLP
      age, half life, and turnover time show that GLP was equivalently removed through
      hydrolysis and oxidation, but the latter produced AMPA. Biodegradation processes
      in the root zone removed more than 90% of applied GLP and more than 23% of the
      produced AMPA between two consecutive applications. Doubling organic carbon
      availability enhanced GLP and AMPA biodegradation, especially GLP hydrolysis to
      sarcosine. This work highlights that GLP and AMPA removal is controlled by soil
      water dynamics that depend on ecohydrological boundary conditions, and by carbon
      sources availability to biodegraders.

PMID- 30223109
TI  - Cellular uptake and apoptotic potential of rhenium labeled magnetic protein cages
      in MDA-MB-231 cells.
AB  - 188Re-magnetoferritin nanoparticles (NPs) provide an attractive platform for
      localized radiation therapy due to their magnetic targeting capability while
      enhancing contrast in magnetic resonans imaging (MRI) signals. In this study,
      cellular uptake, in vitro cytotoxicity, apoptotic potential of a non-radioactive
      isotope of rhenium in the form of 187Re-magnetoferritin NPs were evaluated in
      both human normal mammary epithelial and breast metastatic adenocarcinoma cell
      lines. The results showed that, NP administration into the cells is through
      receptor mediated endocytosis and cancer cells displayed significantly higher
      uptake and cytotoxicity compared to normal cells. IC50 values of nanoparticles
      were calculated as 0.96 mg/mL for cancer and 1.73 mg/mL for normal cells. Annexin
      V/ Propidium Iodide (PI) staining also showed that, NPs induced higher apoptotic
      rates in cancer cells compared to normal cells. Gene expression analyses
      confirming the results showed that, pro-apoptotic PUMA and BAX genes were
      significantly up-regulated while anti-apoptotic BCL-2 and SURVIVIN genes were
      down-regulated in cancer cells compared to normal cells. Overall, these in vitro
      results suggest that, 187Re-magnetoferritin NPs have a promising potential for
      cancer therapy and can be used for imaging and diagnostic purposes for breast
      cancer at concentrations lower than 0.96 mg/mL. At concentrations above 1 mg/mL,
      NPs induce apoptosis which can also be used for cancer treatments.

PMID- 30223110
TI  - Student preferences and perceptions of learning from vSIM for NursingTM.
AB  - This study explored BSN students' perceptions of learning with vSim for
      NursingTM. Using a mixed methods design with 99 students, key points of learning
      were medication administration and respiratory interventions. Qualitative data
      demonstrated learning of assessment, prioritization, and emergency management.
      The top student preferences of how to use virtual simulation were as a clinical
      makeup or to enhance lecture. The findings support the use of virtual simulation
      and provide data to guide nurse educators to more strategically integrate virtual
      simulation exercises.

PMID- 30223111
TI  - Paramedic academics in Australia and New Zealand: The 'no man's land' of
      professional identity.
AB  - Those transitioning from practice to academia can struggle with the perception
      that they might lose their hard-won and deeply-held professional identity, while
      grappling with the difficulty of creating an academic identity. This is a common
      experience for those entering universities with strong clinical identities.
      Paramedics, as members of an emerging health profession, share these challenges
      with nursing and allied health professionals. In this study of paramedic
      academics in Australia and New Zealand, a majority did not consider themselves to
      still be paramedics on the basis that they were no longer clinically active. Nor
      did they consider themselves to be academics as most lacked doctoral
      qualifications and associated scholarly achievements that made them feel worthy
      of a place in the 'academy'. This lack of a professional identity as either a
      paramedic or an academic places them in a 'no man's land' of professional
      identity. Many are unable to effectively fuse their paramedic and academic
      identities to become comfortable as 'paramedic academics'. For this to change,
      there needs to be a partnership between the paramedicine discipline and
      universities to ensure that paramedics entering academia have a recognised and
      valued career pathway and are better prepared to make the transition to academia.

PMID- 30223112
TI  - Colonic MicroRNA Profiles, Identified by a Deep Learning Algorithm, That Predict
      Responses to Therapy of Patients With Acute Severe Ulcerative Colitis.
AB  - BACKGROUND & AIMS: Acute severe ulcerative colitis (ASUC) is a life-threatening
      condition managed with intravenous steroids followed by infliximab, cyclosporine,
      or colectomy (for patients with steroid resistance). There are no biomarkers to
      identify patients most likely to respond to therapy; ineffective medical
      treatment can delay colectomy and increase morbidity and mortality. We aimed to
      identify biomarkers of response to medical therapy for patients with ASUC.
      METHODS: We performed a retrospective analysis of 47 patients with ASUC, well
      characterized for their responses to steroids, cyclosporine, or infliximab,
      therapy at 2 centers in France. Fixed colonic biopsies, collected before or
      within the first 3 days of treatment, were used for microarray analysis of
      microRNA expression profiles. Deep neural network-based classifiers were used to
      derive candidate biomarkers for discriminating responders from non-responders to
      each treatment and to predict which patients would require colectomy. Levels of
      identified microRNAs were then measured by quantitative PCR analysis in a
      validation cohort of 29 independent patients-the effectiveness of the
      classification algorithm was tested on this cohort. RESULTS: A deep neural
      network-based classifier identified 9 microRNAs plus 5 clinical factors,
      routinely recorded at time of hospital admission, that associated with responses
      of patients to treatment. This panel discriminated responders to steroids from
      non-responders with 93% accuracy (area under the curve, 0.91). We identified 3
      algorithms, based on microRNA levels, that identified responders to infliximab vs
      non-responders (84% accuracy, AUC = 0.82) and responders to cyclosporine vs non
      responders (80% accuracy, AUC = 0.79). CONCLUSION: We developed an algorithm that
      identifies patients with ASUC who respond vs do not respond to first- and second
      line treatments, based on microRNA expression profiles in colon tissues.

PMID- 30223113
TI  - Atopic dermatitis in African American patients is TH2/TH22-skewed with TH1/TH17
      attenuation.
AB  - BACKGROUND: African Americans (AA) are disproportionately impacted by atopic
      dermatitis (AD), with increased prevalence and therapeutic challenges unique to
      this population. Molecular profiling data informing development of targeted
      therapeutics for AD are derived primarily from European American (EA) patients.
      These studies are absent in AA, hindering development of effective treatments for
      this population. OBJECTIVE: We sought to characterize the global molecular
      profile of AD in the skin of AA patients as compared with that of EA AD and
      healthy controls. METHODS: We performed RNA-Seq with reverse transcription
      polymerase chain reaction validation and immunohistochemistry studies in lesional
      and nonlesional skin of AA and EA AD patients vs healthy controls. RESULTS:
      African American AD lesions were characterized by greater infiltration of
      dendritic cells (DCs) marked by the high-affinity immunoglobulin E (IgE) receptor
      (FcepsilonR1+) compared with EA AD (P < .05). Both AD cohorts showed similarly
      robust up-regulation of Th2-related (CCL17/18/26) and Th22-related markers
      (interleukin [IL]-22, S100A8/9/12), but AA AD featured decreased expression of
      innate immune (tumor necrosis factor [TNF], IL-1beta), Th1-related (interferon
      gamma [IFN-gamma], MX1, IL-12RB1), and Th17-related markers (IL-23p19, IL-36G,
      CXCL1) vs EA AD (P < .05). The Th2 (IL-13) and Th22-related products (IL-22,
      S100A8/9/12) and serum IgE were significantly correlated with clinical severity
      (Scoring of Atopic Dermatitis [SCORAD]) in AA. Fillagrin (FLG) was exclusively
      down-regulated in EA AD, whereas loricrin (LOR) was down-regulated in both AD
      cohorts and negatively correlated with SCORAD in AA. CONCLUSION: The molecular
      phenotype of AA AD skin is characterized by attenuated Th1 and Th17 but similar
      Th2/Th22-skewing to EA AD. Our data encourages a personalized medicine approach
      accounting for phenotype-specific characteristics in future development of
      targeted therapeutics and clinical trial design for AD.

PMID- 30223114
TI  - An in-depth characterization of a large cohort of adult patients with
      eosinophilic esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, allergic, immune
      mediated disease associated with increased risk of comorbid atopic conditions.
      OBJECTIVE: To perform an in-depth characterization of a large cohort of manually
      verified adult patients with EoE, including evaluation of less studied
      associations, such as pollen food allergy syndrome, anaphylaxis, autoimmunity,
      and psychiatric comorbidities. METHODS: We performed a manual retrospective
      electronic medical record review of 1,218 patients with EoE identified by
      International Classification of Diseases, Ninth Revision and International
      Classification of Disease, 10th Revision codes from the University of
      Pennsylvania Health Systems. Through manual medical record review, we evaluated
      patient demographics, family and smoking history, laboratory and endoscopic
      findings, treatment, and comorbid atopic, autoimmune, and psychiatric conditions.
      RESULTS: A total of 950 of the 1,218 patients had biopsy-proven EoE. This cohort
      was predominantly male, white, and never-smokers who presented most commonly with
      dysphagia, with an initial biopsy results showing 49 eosinophils per high-powered
      field, a serum absolute eosinophilic count of 446,000/uL, and mean total IgE
      level of 243 IU/mL. Of the patients, 55% had impaction (of which 38% required
      endoscopic removal), and 56% had strictures or fibrosis (of which 56% underwent
      dilatation). Therapy used was predominantly (77%) medical only. Comorbid atopy,
      pollen food allergy syndrome, drug allergy, anaphylaxis, autoimmunity, and
      psychiatric illnesses were higher in the EoE cohort compared with the general
      University of Pennsylvania Health Systems population. CONCLUSION: Our adult
      cohort of manually verified, biopsy-proven EoE had an increased risk of pollen
      food allergy syndrome, anaphylaxis, and comorbid autoimmune and psychiatric
      conditions compared with the University of Pennsylvania Health Systems
      population. There was also an increased prevalence of impaction and stricture or
      fibrosis requiring endoscopic intervention compared with the pediatric
      population.

PMID- 30223115
TI  - Asthma phenotypes based on health services utilization for allergic diseases in a
      province-wide birth cohort.
AB  - BACKGROUND: Previous studies on asthma phenotypes were often conducted in
      selected clinical populations and overlooked changes over the life course.
      OBJECTIVE: In a population-based cohort, we identified asthma phenotypes based on
      utilization of health services for allergic diseases in three life periods and
      documented transitions between phenotypes across life periods. METHODS: In a
      cohort of 78,211 individuals born in 1974 in the province of Quebec (Canada), we
      documented medical visits and hospitalizations for asthma and other allergic
      diseases until 1994. Phenotypes based on clusters of health services utilization
      in childhood (8-12 years), adolescence (13-17 years), and young adulthood (18-20
      years) were identified using Ward's method among 9,989 (12.8%) subjects who had
      at least one health encounter for asthma during follow-up. Population level
      probabilities of transitioning between phenotypes were estimated in the full
      study population. RESULTS: In the subset with asthma, six phenotypes were
      identified during both childhood and young adulthood, and seven during
      adolescence. The most common phenotype was "no asthma or allergic diseases": 58%
      in childhood, 42% in adolescence, and 54% in adulthood. Second most common was
      the "mild asthma/no allergic diseases" phenotype, representing respectively 36%,
      31%, and 21% in these three periods. In the study population, 87% of the subjects
      remained in the "no asthma" phenotype over the follow-up. The vast majority of
      subjects in the asthma phenotypes transitioned over time. CONCLUSION: Our study
      uniquely contributes to a better understanding, at the population level, of the
      manifestations and transitions in asthma phenotypes over the life course.

PMID- 30223116
TI  - Development of novel amide-derivatized 2,4-bispyridyl thiophenes as highly potent
      and selective Dyrk1A inhibitors. Part II: Identification of the cyclopropylamide
      moiety as a key modification.
AB  - Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) is a
      potential target in Alzheimer's disease (AD) because of the established
      correlation between its over-expression and generation of neurofibrillary tangles
      (NFT) as well as the accumulation of amyloid plaques. However, the use of Dyrk1A
      inhibitors requires a high degree of selectivity over closely related kinases. In
      addition, the physicochemical properties of the Dyrk1A inhibitors need to be
      controlled to enable CNS permeability. In the present study, we optimized our
      previously published 2,4-bispyridyl thiophene class of Dyrk1A inhibitors by the
      synthesis of a small library of amide derivatives, carrying alkyl, cycloalkyl, as
      well as acidic and basic residues. Among this library, the cyclopropylamido
      modification (compound 4b) was identified as being highly beneficial for several
      crucial properties. 4b displayed high potency and selectivity against Dyrk1A over
      closely related kinases in cell-free assays (IC50: Dyrk1A = 3.2 nM; Dyrk1B = 72.9
      nM and Clk1 = 270 nM) and inhibited the Dyrk1A activity in HeLa cells with high
      efficacy (IC50: 43 nM), while no significant cytotoxicity was observed. In
      addition, the cyclopropylamido group conferred high metabolic stability and
      maintained the calculated physicochemical properties in a range compatible with a
      potential CNS activity. Thus, based on its favourable properties, 4b can be
      considered as a candidate for further in vivo testing in animal models of AD.

PMID- 30223117
TI  - Discovery of novel human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2)
      inhibitors as potential anticancer agents.
AB  - The enzyme inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes an essential
      step in the de novo biosynthesis of guanine nucleotides, and thus regulates the
      guanine nucleotide pool required for cell proliferation. Of the two isoforms,
      human IMPDH type 2 (hIMPDH2) is a validated molecular target for potential
      immunosuppressive, antiviral and anticancer chemotherapy. In search of newer
      hIMPDH2 inhibitors as potential anticancer agents, three novel series (A: 5
      aminoisobenzofuran-1(3H)-one, B: 3,4-dimethoxyaniline and C: benzo[d]-[1,3]dioxol
      5-ylmethanamine) were synthesized and evaluated for in vitro and cell-based
      activities. A total of 37 molecules (29-65) were screened for their in vitro
      hIMPDH2 inhibition, with particular emphasis on establishing their structure
      activity relationship (SAR) trends. Eight compounds (hits, 30, 31, 33-35, 37, 41
      and 43) demonstrated significant enzyme inhibition (>70% @ 10 MUM); especially
      the A series molecules were more potent than B series (<70% inhibition @ 10 MUM),
      while C series members were found to be inactive. The hIMPDH2 IC50 values for the
      hits ranged from 0.36 to 7.38 MUM. The hits displaying >80% hIMPDH2 inhibition
      (30, 33, 35, 41 and 43) were further assessed for their cytotoxic activity
      against cancer cell lines such as MDA-MB-231 (breast adenocarcinoma), DU145
      (prostate carcinoma), U87 MG (glioblastoma astrocytoma) and a normal cell line,
      NIH-3T3 (mouse embryonic fibroblast) using MTT assay. Most of the compounds
      exhibited higher cellular potency against cancer cell lines and notably lower
      toxicity towards NIH-3T3 cells compared to mycophenolic acid (MPA), a
      prototypical hIMPDH2 inhibitor. Two of the series A hits (30 and 35) were
      evaluated in human peripheral blood mononuclear cells (hPBMC) assay and found to
      be better tolerated than MPA. The calculated/predicted molecular and
      physicochemical properties were satisfactory with reference to drug-likeness. The
      molecular docking studies clearly demonstrated crucial interactions of the hits
      with the cofactor-binding site of hIMPDH2, further providing critical information
      for refining the design strategy. The present study reports the design and
      discovery of structurally novel hIMPDH2 inhibitors as potential anticancer agents
      and provides a guide for further research on the development of safe and
      effective anticancer agents, especially against glioblastoma.

PMID- 30223118
TI  - Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea
      derivatives as novel P2Y1 receptor antagonists.
AB  - A novel series of 2-(phenoxyaryl)-3-urea derivatives were designed, synthesized,
      and biologically evaluated for their anti-thrombotic activity. Most of compounds
      exhibited good inhibition against P2Y1 receptor. Among them, three compounds 11,
      12, and 13 demonstrated good P2Y1 receptor antagonistic potency in vitro (IC50 =
      0.62 MUM, 0.82 MUM, and 0.21 MUM, respectively). In antiplatelet aggregation
      study, four compounds 2, 3, 9, and 13 showed good antiplatelet activity. The
      possible binding modes of compounds with P2Y1 receptor were also explored by
      molecular docking simulation. The docking studies demonstrated that compound 13
      interacted well with Phe119 through hydrophobic interaction and modestly improved
      the P2Y1 receptor antagonistic activity, making it justifiable for further
      investigation.

PMID- 30223119
TI  - 4-Hydroxy-1,2,3-triazole moiety as bioisostere of the carboxylic acid function: a
      novel scaffold to probe the orthosteric gamma-aminobutyric acid receptor binding
      site.
AB  - The correct application of bio(iso)steric replacement, a potent tool for the
      design of optimized compounds, requires the continuous development of new
      isosters able to respond to specific target requirements. Among carboxylic acid
      isosters, as the hydroxylated pentatomic heterocyclic systems, the hydroxy-1,2,3
      triazole represents one of the most versatile but less investigated. With the
      purpose to enlarge its bioisosteric application, we report the results of a study
      devoted to obtain potential biomimetics of the gamma-aminobutyric acid (GABA),
      the major inhibitory neurotransmitter in the central nervous system (CNS). A
      series of N1- and N2- functionalized 4-hydroxy-1,2,3-triazole analogues of the
      previous reported GABAAR ligands, including muscimol, 4-PIOL, and 4-PHP has been
      synthesized and characterized pharmacologically. Furthermore, this study led to
      development of straightforward chemical strategies directed to decorate the
      hydroxytriazole core scaffold, opening for further elaborative studies based on
      this system. The unsubstituted N1- and N2-piperidin-4-yl-4-hydroxy-1,2,3-triazole
      analogues (3a, 4a) of 4-PIOL and 4-PHP showed weak affinity (high to medium
      micromolar range), whereas substituting the 5-position of the triazole core with
      a 2-naphthylmethyl or 3,3-diphenylpropyl led to binding affinities in the low
      micromolar range. Based on electrostatic analysis and docking studies using a
      alpha1beta2gamma2 GABAAR homology model we were able to rationalize the observed
      divergence in SAR for the series of N1- and N2- piperidin-4-yl-4-hydroxy-1,2,3
      triazole analogues, offering more detailed insight into the orthosteric GABAAR
      binding site.

PMID- 30223120
TI  - Dual potent ALK and ROS1 inhibitors combating drug-resistant mutants: Synthesis
      and biological evaluation of aminopyridine-containing diarylaminopyrimidine
      derivatives.
AB  - To identify ALK and ROS1 dual inhibitors conferring resistance to ALK secondary
      mutations, especially 'gatekeeper' L1196 M and the most predominant ceritinib
      resistant G1202R mutations, a series of novel 2,4-diarylaminopyrimidine analogues
      were designed and synthesized by incorporating 2-alkoxy-6-alicyclic
      aminopyridinyl motifs. The biological evaluations on cellular and enzymatic
      assays led to identification of compound F-1, which turned out to be effective
      against ALKWT, ROS1WT, ALKL1196M and ALKG1202R kinases with IC50 of 2.1 nM, 2.3
      nM, 1.3 nM and 3.9 nM, respectively, superior to crizotinib and ceritinib.
      Moreover, F-1 exhibited significant cytotoxicity on ALK-addicted Karpas299,
      H2228, and Ba/F3 cell expressing G1202R mutant, as well as ROS1-positive HCC78
      cell with IC50 values ranging from 10 nM to 43 nM. Notably, F-1 was capable of
      suppressing phospho-ALK and its relative downstream signaling pathways, and
      eventually, inducing cell apoptosis in a dose-dependent manner in Karpas-299
      cell. Together, F-1 is validated as a promising ALK/ROS1 dual inhibitor great
      potential for G1202R ALK mutation cancers.

PMID- 30223121
TI  - Synthesis and evaluation of new designed multiple ligands directed towards both
      peroxisome proliferator-activated receptor-gamma and angiotensin II type 1
      receptor.
AB  - Because of the complex biological networks, many pathologic disorders fail to be
      treated with a molecule directed towards a single target. Thus, combination
      therapies are often necessary, but they have many drawbacks. An alternative
      consists in building molecules intended to interact with multiple targets, called
      designed multiple ligands. We followed such a strategy in order to treat
      metabolic syndrome, by setting up molecules directed towards both type 1
      angiotensin II (AT1) receptor and peroxisome proliferator-activated receptor
      gamma (PPAR-gamma). For this purpose, many molecules were prepared by merging
      both pharmacophores following three different strategies. Their ability to
      activate PPAR-gamma and to block AT1 receptors were evaluated in vitro. This
      strategy led to the preparation of many new PPAR-gamma activating and AT1
      blocking molecules. Among them, some exhibited both activities, highlighting the
      convenience of this approach.

PMID- 30223122
TI  - Identification of dual Sigma1 receptor modulators/acetylcholinesterase inhibitors
      with antioxidant and neurotrophic properties, as neuroprotective agents.
AB  - In this manuscript we report on the design, synthesis and evaluation of dual
      Sigma 1 Receptor (S1R) modulators/Acetylcholinesterase (AChE) inhibitors endowed
      with antioxidant and neurotrophic properties, potentially able to counteract
      neurodegeneration. The compounds based on arylalkylaminoketone scaffold integrate
      the pharmacophoric elements of RRC-33, a S1R modulator developed by us,
      donepezil, a well-known AChE inhibitor, and curcumin, a natural antioxidant
      compound with neuroprotective properties. A small library of compounds was
      synthesized and preliminary in vitro screening performed. Some compounds showed
      good S1R binding affinity, selectivity towards S2R and N-Methyl-d-Aspartate
      (NMDA) receptor, AChE relevant inhibiting activity and are potentially able to
      bypass the BBB, as predicted by the in silico study. For the hits 10 and 20, the
      antioxidant profile was assessed in SH-SY5Y human neuroblastoma cell lines by
      evaluating their protective effect against H2O2 cytotoxicity and reactive oxygen
      species (ROS) production. Tested compounds resulted effective in decreasing ROS
      production, thus ameliorating the cellular survival. Moreover, compounds 10 and
      20 showed to be effective in promoting the neurite elongation of Dorsal Root
      Ganglia (DRG), thus demonstrating a promising neurotrophic activity. Of note, the
      tested compounds did not show any cytotoxic effect at the concentration assayed.
      Relying on these encouraging results, both compounds will undergo a structure
      optimization program for the development of therapeutic candidates for
      neurodegenerative diseases treatment.

PMID- 30223124
TI  - Biological CNP removal from meat-processing wastewater in an innovative high rate
      up-flow A2O bioreactor.
AB  - A high rate up-flow anaerobic, anoxic and oxic (A2O) bioreactor was designed and
      operated for meat-processing wastewater (MPW) treatment as a single cost
      effective system with the aim of simultaneous CNP removal. The influence of three
      essential factors, HRT, COD/TN ratio and aerated volume fraction on the reactor
      performance was assessed using response surface methodology (RSM). The required
      HRT to reach 98.5% COD removal was achieved at 7.5 h. Simultaneous CNP removal
      under denitrification rate of 199.4 mg/l.d gave high nitrate to nitrogen gas
      conversion of 74.6 mg/l. An HRT, COD/TN ratio and aerated volume fraction of 10
      h, 100:20 and 60%, respectively, was a favored condition for an efficient
      nitrogen removal with effluent total Kjeldahl nitrogen (TKN) less than 70 mg/l.
      Under optimum condition, an HRT, COD/TN and aerated volume fraction of 8 h,
      100:14 and 65%, respectively, resulted an effluent phosphorus of 43 mg/l, but
      93.97 mg/l phosphorus was released in an anaerobic condition at 6 h. An effluent
      with a low turbidity of about 1.5 NTU and a sludge volume index (SVI) of 75.9
      ml/g was achieved using at HRT of 12.5 h, COD/TN ratio of 100: 8 and aerated
      volume fraction of 50%. Under these conditions, the removal efficiencies for COD,
      TKN, nitrate-nitrogen (NO3--N), total nitrogen (TN) and phosphorus (PO43--P) were
      obtained to be 98.33, 92.06, 91.97, 90.48 and 83.48%, respectively. As a result,
      the application of the up-flow A2O bioreactor is a promising configuration to get
      hygienic water from wastewater.

PMID- 30223123
TI  - Advances in diarylpyrimidines and related analogues as HIV-1 nonnucleoside
      reverse transcriptase inhibitors.
AB  - HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) have been playing
      an important role in the fight against acquired immunodeficiency syndrome (AIDS).
      Diarylpyrimidines (DAPYs) as the second generation NNRTIs, represented by
      etravirine (TMC125) and rilpivirine (TMC278), have attracted extensive attention
      due to their extraordinary potency, high specificity and low toxicity. However,
      the rapid emergence of drug-resistant virus strains and dissatisfactory
      pharmacokinetics of DAPYs present new challenges. In the past two decades, an
      increasing number of novel DAPY derivatives have emerged, which significantly
      enriched the structure-activity relationship of DAPYs. Studies of crystallography
      and molecular modeling have afforded a lot of useful information on structural
      requirements of NNRTIs, which contributes greatly to the improvement of their
      resistance profiles. In this review, we reviewed the discovery history and their
      evolution of DAPYs including their structural modification, derivatization and
      scaffold hopping in continuous pursuit of excellent anti-HIV drugs. And also, we
      discussed the prospect of DAPYs and the directions of future efforts.

PMID- 30223125
TI  - Crude oil cardiotoxicity to red drum embryos is independent of oil dispersion
      energy.
AB  - The potential bioavailability of toxic chemicals from oil spills to water column
      organisms such as fish embryos may be influenced by physical dispersion along an
      energy gradient. For example, a surface slick with minimal wave action (low
      energy) could potentially produce different toxic effects from high energy
      situations such as pressurized discharge from a blown wellhead. Here we directly
      compared the toxicity of water accommodated fractions (WAFs) of oil prepared with
      low and high mixing energy (LEWAFs and HEWAFs, respectively) using surface oil
      samples collected during the 2010 Deepwater Horizon spill, and embryos of a
      representative nearshore species, red drum (Sciaenops ocellatus). Biological
      effects of each WAF type was quantified with several functional and morphological
      indices of developmental cardiotoxicity, providing additional insight into
      species-specific responses to oil exposure. Although the two WAF preparations
      yielded different profiles of polycyclic aromatic hydrocarbons (PAHs),
      cardiotoxic phenotypes were essentially identical. Based on benchmark thresholds
      for both morphological and functional cardiotoxicity, in general LEWAFs had lower
      thresholds for these phenotypes than HEWAFs based on total PAH measures. However,
      HEWAF and LEWAF toxicity thresholds were more similar when calculated based on
      estimates of dissolved PAHs only. Differences in thresholds were attributable to
      the weathering state of the oil samples.

PMID- 30223126
TI  - Biochar does not attenuate triclosan's impact on soil bacterial communities.
AB  - Triclosan, a broad-spectrum antimicrobial, has been widely used in pharmaceutical
      and personal care products. It undergoes limited degradation during wastewater
      treatment and is present in biosolids, most of which are land applied in the
      United States. This study assessed the impact of triclosan (0-100 mg kg-1) with
      and without biochar on soil bacterial communities. Very little 14C-triclosan was
      mineralized to 14CO2 (<7%) over the course of the study (42 days). While biochar
      (1%) significantly lowered mineralization of triclosan, analysis of 16S rRNA gene
      sequences revealed that biochar impacted very few OTUs and did not alter the
      overall structure of the community. Triclosan, on the other hand, significantly
      affected bacterial diversity and community structure (alpha diversity, ANOVA, p <
      0.001; beta diversity, AMOVA, p < 0.01). Dirichlet multinomial mixtures (DMM)
      modeling and complete linkage clustering (CLC) revealed a dose-dependent impact
      of triclosan. Non-Parametric Metastats (NPM) analysis showed that 150 of 734 OTUs
      from seven main phyla were significantly impacted by triclosan (adjusted p <
      0.05). Genera harboring opportunistic pathogens such as Flavobacterium were
      enriched in the presence of triclosan, as was Stenotrophomonas. The latter has
      previously been implicated in triclosan degradation via stable isotope probing.
      Surprisingly, Sphingomonads, which include well-characterized triclosan degraders
      were negatively impacted by even low doses of triclosan. Analyses of published
      genomes showed that triclosan resistance determinants were rare in Sphingomonads
      which may explain why they were negatively impacted by triclosan in our soil.

PMID- 30223127
TI  - Electrochemical oxidation for stormwater disinfection: How does real stormwater
      chemistry impact on pathogen removal and disinfection by-products level?
AB  - Preliminary laboratory work has shown that electrochemical oxidation (ECO) is a
      promising technology for disinfection of harvested stormwater. This paper focuses
      on understanding how stormwater chemistry (e.g. pH, chloride, bicarbonate,
      ammonia and total organic carbon - that can vary substantially between sites)
      impacts the disinfection performance of ECO. Real stormwater samples from four
      different urban catchments were collected and tested for ECO performance in
      disinfecting stormwater pathogens using a boron doped diamond anode under the
      current density of 4.2 mA/cm2. Results showed that total disinfection of
      indigenous Escherichia coli (E. coli), as well as three different stormwater
      pathogens (Enterococci, Campylobacter and C. perfringens) was achievable for all
      four tested stormwater within 30 min. Compared to the synthetic stormwater, lower
      disinfection rates were observed in real stormwater which has more complex
      chemistry. Stormwater chloride concentration was the only tested parameter that
      had significant impact on the treatment performance, with higher initial
      stormwater chloride concentration leading to an increased disinfection rate.
      Disinfection by-products in the treated stormwater were well below the Australian
      Drinking Water Guideline value for health, with its production level positively
      correlated to the pH values of stormwater.

PMID- 30223128
TI  - Effect of redox state of Ag on indoor formaldehyde degradation over Ag/TiO2
      catalyst at room temperature.
AB  - Ag/TiO2 catalysts were prepared via in-situ synthesis and impregnation methods.
      The effect of redox state of Ag species on catalytic activity of Ag/TiO2
      catalysts was studied. The Ag-i-300 catalyst with partially oxidized state of Ag
      species shows superior catalytic activity, keeping HCHO removal efficiency at an
      extraordinary level of 100% during the 200 min's reaction. The Ag/TiO2 catalysts
      were characterized by XPS, UV-Vis, BET, XRD, TEM, and in-situ DRIFTS
      technologies. XPS and TEM results exhibit that the partially oxidized state of
      Agdelta+ (0 < delta < 1) and high dispersion of Ag species are beneficial for the
      oxidation of HCHO over Ag/TiO2 catalysts. According to the above results, a
      reaction pathway for HCHO oxidation over Ag-i-300 catalyst was also proposed.

PMID- 30223129
TI  - Biological treatment of wastewater polluted with an oxyfluorfen-based commercial
      herbicide.
AB  - Fluoxil-24 is a commercial herbicide based on oxyfluorfen (a hazardous non
      soluble organochlorinated compound) and additional compounds used as solvents.
      The aim of this work is to study the biotreatability of this commercial herbicide
      in water through batch experiments performed at different temperatures (15, 20,
      25 and 30  degrees C) and initial concentrations (85, 150, 300 and 500 mg L-1 of
      oxyfluorfen). Activated sludge from an oil refinery wastewater treatment plant
      was acclimated and used for biodegradation experiments. Two main mechanisms,
      volatilization and biodegradation, were observed to be responsible of the
      herbicide removal. Fluoxil-24 removal efficiencies between approximately 40% and
      80% were reached after 70 h, depending on the conditions used, and oxyfluorfen
      was not completely removed. Regarding the influence of the temperature, thermal
      inhibition problems appeared at 30  degrees C, and the volatilization rate of
      solvents increased, causing oxyfluorfen to become unavailable for microorganisms.
      An increase of herbicide initial concentration did not clearly affect the
      herbicide removal efficiency, whereas it negatively affected the biological
      mechanism. The experimental results were fitted to a mathematical model that
      included both simultaneous mechanisms of volatilization and Monod biodegradation
      kinetics. The model was able to predict the experimental results, and the
      calculated model parameters confirmed the effect of the variables under study.

PMID- 30223130
TI  - Gestational 1-nitropyrene exposure causes fetal growth restriction through
      disturbing placental vascularity and proliferation.
AB  - 1-Nitropyrene (1-NP) is a widely distributed pollutant in the environment and is
      best known for its mutagenicity and carcinogenicity. In this study, we evaluated
      the effects of 1-NP exposure in different gestational stages on the pregnant
      outcomes. Pregnant mice were administered with 1-NP by gavage daily in early (GD1
      GD6), middle (GD7-GD12) or late pregnancy (GD13-GD17), respectively. We found
      that gestational 1-NP exposure had no effect on implantation sites per litter,
      preterm delivery and fetal death. Interestingly, mice exposed to 1-NP in late
      pregnancy showed a significant reduction in fetal weight and crown-rump length.
      Correspondingly, placental weight and diameter were markedly reduced in dams
      exposed to 1-NP in late pregnancy. Additional experiment showed maternal 1-NP
      exposure in late pregnancy reduced blood sinusoid area of placental labyrinthine
      region in a dose-dependent manner. Although gestational 1-NP exposure had little
      effect on placental cell apoptosis, as determined by the TUNEL assay, the rate of
      Ki67-positive cell, a marker of cell proliferation, was reduced in placental
      labyrinthine region of mice exposed to 1-NP in late pregnancy. These findings
      provide evidence that gestational 1-NP exposure induces fetal growth restriction
      in a stage-dependent manner. Placenta is a toxic target in the process of 1-NP
      induced fetal growth restriction.

PMID- 30223131
TI  - Impact of antimicrobial silver nanoparticles on anode respiring bacteria in a
      microbial electrolysis cell.
AB  - This study assessed the impact of antimicrobial AgNPs (50 mg L-1, 30-50 nm) on
      the electrocatalytic activity of a mixed-culture anode biofilm enriched with
      Geobacter species. The current densities and electrochemical kinetics were
      maintained after exposure to AgNPs in consecutive fed-batch cycles, despite
      significant changes in morphological structures and bacterial communities.
      Bacterial community analysis showed a substantial increase in the Geobacter
      population in response to AgNPs exposure, indicating their higher tolerance to
      AgNPs. In contrast, the population of other anode respiring bacteria (ARB)
      belongs to Acinetobacter, Dysgonomonas, and Cloacibacillus genera appeared to be
      very sensitive to AgNPs toxicity as their relative abundance significantly
      decreased. Microscopic imaging showed that AgNPs were accumulated within anode
      biofilm matrix without penetration inside the cells. Moreover, the anode biofilm
      became denser because of enhanced extracellular polymeric substances (EPSs)
      production by ARB after exposure of AgNPs, implying that EPS could protect ARB
      against AgNPs toxicity.

PMID- 30223132
TI  - Free ammonia-based pretreatment enhances phosphorus release and recovery from
      waste activated sludge.
AB  - The recovery of phosphorus from waste activated sludge (WAS) was usually at low
      levels due to low phosphorus release. This study presents a novel, cost-effective
      and eco-friendly pretreatment method, e.g., using free ammonia (FA) to pretreat
      WAS, to enhance the phosphorus release from WAS. Experimental results showed that
      the phosphorus release from WAS was significantly increased after FA pretreatment
      at up to 189.4 mg NH3-N L-1 for 24 h, under which the released PO43--P (i.e.
      101.6 +/- 6.7 mg L-1) was higher than that pH 9 (i.e. 62.6 +/- 4.54 mg L-1) and
      control (without pH and FA pretreatment) (i.e. 15.1 +/- 1.86 mg L-1). More
      analysis revealed that the FA induced improvement in phosphorus release could be
      attributed to the disintegration of extracellular polymeric substances (EPS) and
      cell envelope of sludge cells. Moreover, the released phosphorus recovered as
      magnesium ammonium phosphate (MAP) was confirmed. The findings reported may guide
      engineers to develop an economic and practical strategy to enhance resources and
      energy recovery from WAS.

PMID- 30223133
TI  - Influence of demographic and clinical characteristics of elderly patients with a
      hip fracture on mortality: A retrospective, total cohort study in North-East
      Spain.
AB  - IMPORTANCE: The increased mortality after hip fracture (HF) is caused by multiple
      factors, and large samples are needed to assess the weight of each factor. To
      date, few studies have investigated these factors through a total cohort
      approach, and the complexity of underlying medical conditions has not been
      considered. OBJECTIVE: To investigate the influence of demographic and clinical
      characteristics on increased mortality risk in elderly patients with hip fracture
      (HF). DESIGN: Retrospective, total cohort study collecting 4-year data. SETTING:
      All hospitals and primary care units owned by, or associated with, Catalonia's
      local health department (CatSalut) (north-east Spain). PARTICIPANTS: All patients
      aged >=65 years, admitted to Catalan hospitals from CatSalut because of a HF
      between 1st January 2012 and 31st December 2015. EXPOSURE: Hip fracture. MAIN
      OUTCOME MEASURES: The main outcome was survival. Measures regarding demographic
      and clinical characteristics at the moment of hospital admission included age,
      sex, osteoporosis treatment, previous fractures, type of intervention,
      nutritional status, and comorbidities. Patients were stratified using the
      Adjusted Morbidity Groups (GMA) risk assessment tool. RESULTS: Of the 30,552
      patients included in the study sample, 10,439 (34%) died during follow-up, 6821
      (22%) within the first year after hospital admission. Mean (SD) age was 84 (7)
      years; 75% were female. Baseline factors with greater influence on survival were
      age (HRs 1.44 [95% CI 1.22-1.70], 2.38 [2.03-2.79], and 4.38 [3.73-5.15] for age
      groups 70-79, 80-89, and >89, respectively), underweight (HR 1.65 [1.36-2.01]),
      lack of surgical intervention (HR 2.64 [2.47-2.83]), and very high risk stratum
      of GMA risk (HR 1.58 [1.45-1.73]). Vitamin D/calcium supplementation and
      osteoporosis treatment showed a significant but moderate influence on mortality
      (HRs 0.84 (0.79-0.88) and 0.92 [0.85-0.99], respectively). CONCLUSIONS AND
      RELEVANCE: In elderly patients with HF, age and health status factors at hospital
      admission have the greatest impact on mortality risk after hospital admission.
      Our findings encourage a comprehensive intervention aimed at improving underlying
      medical conditions of HF patients.

PMID- 30223134
TI  - Bone health evaluation one year after aromatase inhibitors completion.
AB  - INTRODUCTION: Breast cancer patients treated with aromatase inhibitors (AIs)
      experience increased bone loss during their treatment. However, there is little
      information about bone mineral density (BMD) after completing AI-treatment. The
      present study aimed to assess BMD changes one year after AI-therapy completion.
      METHODS: Data were collected from 864 postmenopausal women treated with AI during
      5 years (5y-AI group), or during 2-3 years after taking tamoxifen therapy (pTAM
      AI group). Participants with osteoporosis were treated with oral bisphosphonates
      (BP). BMD changes in lumbar spine (LS), femoral neck (FN) and total hip (TH)
      between baseline, end of treatment, and at one year post-treatment were assessed
      using repeated-measures ANOVA. RESULTS: At the end of AI-treatment, 382 patients
      had available BMD values and 316 also had post-treatment BMD values. As expected,
      BMD levels were decreased at AI-completion in non-BP treated patients. After one
      year, LS BMD increased in both groups (5y-AI: +2.11% [95%CI: 1.55 to 2.68], p <
      0.001; pTAM-AI: +1.00% [95%CI: 0.49 to 1.51], p < 0.001) compared with the end of
      AI-therapy, while values at FN and TH remained stable. On the other hand, BMD
      values of BP-treated patients were increased or maintained at the end of AI
      treatment and also at post-treatment. CONCLUSIONS: At one year after AI
      completion, FN and TH BMD remained reduced in non-BP treated women, while LS BMD
      was recovered in the 5y-AI group and partially recovered in the pTAM-AI group. BP
      treatment increased or maintained BMD values at the end of therapy and at one
      year post-treatment.

PMID- 30223135
TI  - Who loses public health insurance when states pass restrictive omnibus
      immigration-related laws? The moderating role of county Latino density.
AB  - In the United States, there is widespread concern that state laws restricting
      rights for noncitizens may have spillover effects for Latino children in
      immigrant families. Studies into the laws' effects on health care access have
      inconsistent findings, demonstrating gaps in our understanding of who is most
      affected, under what circumstances. Using comparative interrupted time series
      methods and a nationally-representative sample of US citizen, Latino children
      with noncitizen parents from the National Health Interview Survey (2005-2014, n =
      18,118), this study finds that living in counties with higher co-ethnic density
      placed children at greater risk of losing Medicaid and Children's Health
      Insurance Program coverage when their states passed restrictive state omnibus
      immigrant laws. This study is the first to demonstrate the importance of
      examining how the health impacts of immigration-related policies vary across
      local communities.

PMID- 30223136
TI  - Prevalence and risk factors of excessive daytime sleepiness in major depression:
      A study with 703 individuals referred for polysomnography.
AB  - BACKGROUND: To date, few studies have investigated the prevalence and risk
      factors of excessive daytime sleepiness (EDS) in major depression. Thus, the aim
      of the present study was to examine the prevalence and risk factors of EDS in a
      large sample of individuals with major depression. METHODS: Data from 703
      individuals with major depression were retrospectively collected from the sleep
      laboratory research database of Erasme Hospital for analysis. A score of > 10 on
      the Epworth Sleepiness Scale was used as the cut-off for EDS. Logistic regression
      analyses were conducted to examine the clinical and demographic risk factors of
      EDS in major depression. RESULTS: The prevalence of EDS in our sample was 50.8%.
      Multivariate logistic regression analysis revealed that the following were
      significant risk factors of EDS in major depression: non-use of short to
      intermediate half-life benzodiazepine receptor agonists, BMI >= 25 kg/m2, age <
      60 years, C-reactive protein > 7 mg/L, Beck Depression Inventory score >= 16,
      atypical depression, apnea-hypopnea index >= 15/h, and use of selective serotonin
      reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. LIMITATIONS:
      To evaluate EDS, we used the Epworth Sleepiness Scale, which only allows for a
      subjective measure of daytime sleepiness. CONCLUSION: EDS is a common symptom in
      individuals with major depression. In this subpopulation, interventions are
      possible for most risk factors of EDS, which justifies improved management of
      this symptom to avoid its negative consequences.

PMID- 30223139
TI  - Dysfunctional attitudes or extreme response style as predictors of depressive
      relapse and recurrence after mobile cognitive therapy for recurrent depression.
AB  - BACKGROUND: According to previous research, dysfunctional attitudes and/or
      scoring extreme on the end-point anchors of questionnaires of dysfunctional
      thinking predict depressive relapse/recurrence. Evidence that these two methods
      represent a risk for depressive relapse/recurrence is however mixed, due to
      differential or poorly defined concepts. The current study aimed to test the two
      methods. METHODS: Remitted recurrently depressed patients with low residual
      depressive symptoms (N = 264) were recruited as part of a randomized controlled
      trial of the effectiveness of mobile Cognitive Therapy for recurrent depression
      versus treatment as usual. In the current secondary analysis, Cox regression
      models were conducted to test dysfunctional attitudes and extreme responding
      variables (assessed on the Dysfunctional Attitudes Scale [DAS]) as predictors of
      depressive relapse/recurrence within two years after randomization. RESULTS: Data
      from 255 participants were analyzed. Results showed that DAS total scores at
      baseline significantly predicted depressive relapse/recurrence (Hazard Ratio [HR]
      = 1.01, p = .042). An index that reflects endorsement of habitual relative to
      functional responses was a significant predictor of depressive relapse/recurrence
      (HR = 2.11, p = .029). LIMITATIONS: The current study employed a single measure
      to identify extreme responses and dysfunctional attitudes. Secondly, various
      statistical analyses were performed without correcting for multiple testing,
      which in turn increased the likelihood to finding significant results.
      CONCLUSIONS: Current study confirmed both methods: People who scored higher on
      the DAS or had relatively more habitual than functional responses on the extreme
      positive ends of the DAS had a decreased time to depressive relapse/recurrence.

PMID- 30223138
TI  - Sequential risk of depression in children born prematurely: A nationwide
      population- based analysis.
AB  - BACKGROUND: Whether children born prematurely are at a high risk of depression is
      still unknown. The present study examined the risk of depression in children who
      were born prematurely, by analyzing a national cohort in Taiwan. METHODS: All
      premature births between January 1, 2000, and December 31, 2010, by using the
      Taiwan National Health Insurance Research Database. A total of 21,478 preterm
      children and 85,903 full-term children were enrolled in this study. Sex, level of
      urbanization of residential area, and parental occupation were considered. We
      included participants who received a diagnosis of depression in more than two
      clinical visits or were hospitalized due to depression. RESULTS: Preterm children
      had a 2.75-fold higher risk of depression than full-term children (95% confidence
      interval [CI] = 1.58-4.79, p < 0.001). Sex was not likely to be associated with
      depression in this study (p = 0.95). The lowest level of urbanization
      significantly contributed to the risk of depression in preterm children (adjusted
      hazard ratio = 6.8, 95% CI = 1.63-28.46, p < 0.01). Regarding parental
      occupation, preterm children whose parents had blue-collar and other occupations
      had a 3.4- and 6.06-fold higher risk of depression, respectively, compared with
      other children (blue-collar occupations: 95% CI = 1.04-11.15, p < 0.05; other
      occupations: 95% CI = 1.71-21.49, p < 0.01). CONCLUSIONS: Preterm children had a
      2.7-fold higher risk of depression than children born full-term. Early
      identification, timely psychiatric care, intervention strategies, and support for
      their families may reduce the complications of mental illness in preterm
      children.

PMID- 30223140
TI  - Myocardial rupture after small acute myocardial infarction in the absence of
      coronary artery disease.
AB  - A 73-year-old woman with a past medical history of hypertension suffered a
      cardiac arrest. After successful resuscitation, she was hypotensive and
      tachycardic and the ECG showed ST elevation in the inferior and lateral
      precordial leads. Coronary angiography did not show evidence of obstructive
      coronary artery disease. A bedside echocardiogram demonstrated a large
      pericardial effusion with signs of cardiac tamponade. The echocardiogram and
      subsequent aortic root angiography did not reveal evidence of dissection.
      Pericardiocentesis removed 700 cc of bloody fluid with relief of tamponade. A few
      minutes later the patient again arrested. Fluid was again drained but she
      suffered recurrent hemodynamic collapse and could not be resuscitated. Autopsy
      revealed a small transmural myocardial infarction with external rupture and
      hemopericardium. There was only mild coronary artery disease without evidence of
      plaque rupture. This case illustrates that mild coronary artery disease and a
      small myocardial infarction can lead to catastrophic mechanical complications.

PMID- 30223137
TI  - The role of substance use, smoking, and inflammation in risk for suicidal
      behavior.
AB  - BACKGROUND: Alcohol and substance use disorders are important predictors for
      suicidal behavior. However, the role of individual substances as proximal risk
      factors for suicidal behavior and the mechanisms through which substance use
      affect risk are not entirely clear. We examine whether the frequency of substance
      use and whether biological markers in the HPA axis and inflammatory pathways are
      associated with clinical risk factors of suicidal behavior of aggression,
      impulsivity, hopelessness, and poor sleep. METHODS: The sample consisted of
      psychiatric inpatients, aged 15-30 years, admitted for suicide attempt (n = 38),
      suicidal ideation (n = 40); and healthy controls (n = 37). We measured hair
      cortisol concentrations, glucocorticoid receptor (GR) sensitivity, stimulated
      production of interleukin- or IL-6, C-reactive protein, and mRNA expression of
      GR, SKA2, FKBP5, TNF-alpha, and IL-1beta. RESULTS: Smoking was associated with
      increased aggression [beta = 2.9, 95% CI (-0.03, 6), p = 0.05], impulsivity [beta
      = 3.1, 95% CI (1.6, 4.6), p < 0.001], and poor sleep [beta = 0.5, 95% CI (0.03,
      0.95), p = 0.04] even after controlling for demographics and group. Similarly,
      TNF-alpha mRNA was associated with impulsivity [beta = 0.07, 95% CI (0.01, 0.1),
      p = 0.02] and hopelessness [beta = 0.03, 95% CI (0.004, 0.05), p = 0.03]. Smoking
      tobacco (r = 0.32, p < 0.001) was positively associated with TNF-alpha mRNA.
      LIMITATIONS: Study limitations include the cross-sectional design, retrospective
      assessment, and relatively small sample size. CONCLUSIONS: Future longitudinal
      studies are needed to test whether inflammatory markers mediate the relationships
      between smoking, clinical risk factors, and suicidal behavior; and to examine
      whether smoking cessation could reduce the risk for suicidal behavior in at-risk
      patients.

PMID- 30223141
TI  - COX-2 Inhibition mediated anti-angiogenic activatable prodrug potentiates cancer
      therapy in preclinical models.
AB  - Anti-angiogenesis, i.e., blocking the angiogenic pathway, has been considered as
      an important component in current cancer therapeutic modalities. However, the
      associated benefits have proven to be modest as tumor angiogenesis and regrowth
      persist, probably due to other ill-defined complex angiogenic mechanisms. Herein,
      we developed an indomethacin (IMC) incorporating system to mediate hypoxia
      responsive prodrug (TA) and diagnostic agent (DA) in cancer theranostic
      applications. Cyclooxygenase 2 (COX-2) elevated expression in several cancer
      types is closely associated with severe tumor supporting vascularization factors.
      Our strategy utilizing COX-2 inhibition augmented the anti-angiogenetic induced
      hypoxia responsive prodrug activation well. Both in vitro and in vivo results
      proved that DA and TA exhibited specificity towards COX-2 positive (+ve) HeLa and
      A549 cancer cell lines and activation under hypoxic conditions. Compared with
      controls (R1, and anticancer drug SN-38), TA displayed prolonged tumor retention
      and enhanced therapeutic efficacy in xenograft mouse models at a reduced dosage.
      Our results significantly highlighted the importance of COX-2 blockade mediated
      anti-angiogenesis in complementing the hypoxia-responsive drug delivery systems
      (DDSs) and could to beneficial for the rapid development of more efficacious
      antitumor therapeutics.

PMID- 30223142
TI  - SFC for chiral separations in bioanalysis.
AB  - This review covers literature investigating methods for enantioselective
      chromatography using supercritical fluids as mobile phase constituents (SFC) in
      the field of bioanalysis. It provides an overview on method development and
      screening approaches published in scientific literature 2014-2018. Chiral
      stationary phases are used to create a chiral environment that allows for
      discrimination of enantiomers. Especially polysaccharide-based stationary phases
      are used in methods of recent investigations. In comparison to HPLC chiral SFC
      separation provides more selective cavity effects of inclusion-type chiral
      separation phases. Modifier and additive choices as well as further operating
      conditions like backpressure, temperature and flow rate are summarized and
      critically discussed. Further on, observed sample pretreatment and possible
      detection techniques are presented. SFC hyphenated to mass detection was found of
      major relevance and is therefore further discussed. Coupling of SFC with
      different detectors allows for straightforward use in bioanalysis. Interfacing MS
      detectors is generally performed including a make-up pump. Thus, applied make-up
      conditions were also reviewed. While most of the chiral separations in HPLC are
      performed in normal phase mode, and thus, challenge MS hyphenation, SFC-MS
      hyphenation can be easily achieved. This allows for convenient application in
      chiral trace analyses, often required in bioanalysis. Even worse in
      enantioseparation than in achiral chromatography, method development in SFC
      suffers from a lack of knowledge in separation mechanisms and thus approaches are
      often quite unique and most often achieved by screening using a One-Factor-at-a
      Time (OFAT) design. Broad screening experiments with methodical approaches still
      appear as method of choice for now.

PMID- 30223143
TI  - A functional in vitro assay for screening inhibitors of STAT5B phosphorylation.
AB  - Inhibition of STAT phosphorylation is recognized as a viable therapeutic strategy
      for disrupting tumorigenesis. Constitutive STAT phosphorylation is found with
      high frequency in a number of primary tumor types, while non-cancer cells exhibit
      low basal activity, providing an exploitable therapeutic window. STAT activation
      involves phosphorylation of the SH2 domain by a number of tyrosine kinases
      followed by STAT dimerization and translocation to the nucleus. By blocking the
      cognate binding site, STAT SH2-domain inhibitors can impede kinase-mediated de
      novo STAT phosphorylation. Assessing for inhibitors of STAT phosphorylation has
      previously been conducted exclusively in cellulo using Western blot analysis.
      However, while providing useful in cellulo efficacy, it is not possible to
      conclude that inhibition is due to a direct blockade of STAT protein. Here we
      developed a functional assay that directly reports the blockade of
      phosphorylation as a result of inhibitor interaction with STAT proteins. We have
      optimized reaction conditions for the functional assay and validated the assay
      against known STAT5B ligands, including peptides and small molecule inhibitors.
      As part of the study, we have also identified several sites of STAT5B
      phosphorylation by Abl kinase. This assay will serve to delineate the functional
      mechanism of STAT binders in vitro and deconvolute the mechanism of phospho-STAT
      inhibition observed in Western blot analysis.

PMID- 30223144
TI  - Use of ultra-high-performance liquid chromatography coupled with quadrupole-time
      of-flight mass spectrometry system as valuable tool for an untargeted metabolomic
      profiling of Rumex tunetanus flowers and stems and contribution to the
      antioxidant activity.
AB  - Rumex tunetanus is an untapped resource with no available information about their
      chemical composition. That is why, the present study has conducted comprehensive
      metabolites profiling of the hydromethanol extracts of the Rumex tunetanus
      flowers and stems using RP-UHPLC-ESI-QTOF-MS. As results, 60 compounds were
      characterized for the first time in Rumex tunetanus between them, 18
      photochemical were firstly identified in the Polygonaceae family in negative
      ionization mode. In this regard, quercetin-3-O-glucuronide and (-)-epicatechin
      gallate were the most abundant phenolic compounds in flowers and stems,
      respectively. Moreover, positive correlations were found between the antioxidant
      activity measured by DPPH and FRAP assays with the total phenolic compounds (r =
      0.98; r = 0.99, respectively) and the abundance of some phenolic subfamilies such
      as hydroxycinnamic acids, hydroxybenzoic acids, flavonols and flavones with r >
      0.86. The compounds displaying significant (P < 0.01) and good correlations with
      the antioxidant activity (r > 0.93) were hydroxybenzoic acid, rutin, quercetin-3
      O-glucuronide, quercetin-3-O-glucoside, quercetin and luteolin-7-O-rutinoside. In
      conclusion, Rumex tunetanus flowers and stems showed different bioactive compound
      profiles and significant antioxidant properties and could be further used in food
      and nutraceutical industries.

PMID- 30223145
TI  - Genome-wide identification and expression analysis of brassinosteroid
      biosynthesis and metabolism genes regulating apple tree shoot and lateral root
      growth.
AB  - In plants, brassinosteroid biosynthesis and metabolism genes affect endogenous
      brassinosteroid metabolic processes as well as stem and root growth. However,
      there is little information available regarding these genes in apple. In this
      study, 22 brassinosteroid biosynthesis and metabolism genes were identified in
      apple (Malus domestica). These genes were named according to their chromosomal
      locations and the Arabidopsis thaliana homologs. Their conserved characteristic
      domains, evolutionary relationships, syntenic relationships, chemical
      characteristics, gene/protein structures, interactions among the encoded
      proteins, promoter sequences, and functions were investigated. These 22 genes
      were clustered with their A. thaliana homologs based on bioinformatics analyses,
      which suggested they are functionally similar in apple and A. thaliana. Tissue
      specific expression levels revealed that most of these genes are important for
      stem growth and development, while several of these genes affect lateral root
      formation. The transcription patterns of these genes in shoot tips were
      investigated following diverse treatments [brassinosteroid (shoot tips and
      roots), brassinazole, auxin, and temperature]. Gene expression levels were also
      examined in different grafting combinations ('Nagafu No. 2'/Malling 9 and 'Nagafu
      No. 2'/'Nagafu No. 2') and shoot varieties ('Yanfu No. 6' and 'Nagafu No. 2').
      The results indicated that these genes may be involved in apple stem and root
      growth. The comprehensive genome-wide analysis of brassinosteroid biosynthesis
      and metabolism genes presented herein may be useful for breeding new apple
      cultivars with increased vigor. The data also represent a rich genetic resource
      for future apple gene functional investigations that may have implications for
      the genetic improvement of apple tree species.

PMID- 30223146
TI  - Establishment of TUSMi004-A, an induced pluripotent stem cell (iPSC) line from a
      32-year old Chinese Han patient with Obsessive-Compulsive Disorder (OCD).
AB  - A 32-year old Obsessive-Compulsive Disorder (OCD) male patient donated his
      Peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector
      system used to reprogram PBMCs with the human OKSM transcription factors. The
      pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry for
      pluripotency markers and by the ability of the iPSCs to differentiate
      spontaneously into 3 germ layers in vitro. In addition, the iPSC line displayed a
      normal karyotype. Our model might offer a good platform to further study the
      pathological mechanisms, to identify early biomarkers, and also for drug testing
      studies in OCD. Resource Table.

PMID- 30223147
TI  - Auditory (dis-)fluency triggers sequential processing adjustments.
AB  - An increasing amount of studies indicates that experiencing increased task
      demands, triggered for example by conflicting stimulus features or low perceptual
      fluency, lead to processing adjustments. While these demand-triggered processing
      adjustments have been shown for different paradigms (e.g., response conflict
      tasks, perceptual disfluency, task switching, dual tasking), most of them are
      restricted to the visual modality. The present study investigated as to whether
      the challenge to understand speech signals in normal-hearing subjects would also
      lead to sequential processing adjustments if the processing fluency of the
      respective auditory signals changes from trial to trial. To that end, we used
      spoken number words (one to nine) that were either presented with high (clean
      speech) or low perceptual fluency (i.e., vocoded speech as used in cochlear
      implants-Experiment 1; speech embedded in multi-speaker babble noise as typically
      found in bars-Experiment 2). Participants had to judge the spoken number words as
      smaller or larger than five. Results show that the fluency effect (performance
      difference between high and low perceptual fluency) in both experiments was
      smaller following disfluent words. Thus, if it's hard to understand, you try
      harder.

PMID- 30223148
TI  - New azafluorenones with cytotoxic and carbonic anhydrase inhibitory properties: 2
      Aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones.
AB  - New azafluorenones, 2-aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones,
      were prepared to evaluate their cytotoxic/anticancer properties, also their
      inhibitory effects on hCA I and II isoenzymes. Aryl part was changed as [phenyl
      (H1), 4-methylphenyl (H2), 4-methoxyphenyl (H3), 4-fluorophenyl (H4), 4
      bromophenyl (H5), 4-chlorophenyl (H6), 3-hydroxyphenyl (H7), and 4-hydroxyphenyl
      (H8)]. The structure of the synthesized compounds was characterized by 1H NMR,
      13C NMR and HRMS spectra. Cytotoxicity results of the series pointed out that the
      compounds H6 (PSE: 28.0) and H5 (PSE: 27.3), with the highest potency selectivity
      expression (PSE) value, can be considered as leader compounds of the study in
      designing novel anticancer agents. Additionally, all azafluorenones synthesized
      showed a good inhibition profile towards hCA I and II isoenzymes in the range of
      54.14-73.72 nM and 67.28-76.15 nM, respectively. The compounds H5 and H6 can be
      considered for further designs with their cytotoxic and CA inhibitory profiles.

PMID- 30223149
TI  - Pharmacophore mapping, molecular docking, chemical synthesis of some novel
      pyrrolyl benzamide derivatives and evaluation of their inhibitory activity
      against enoyl-ACP reductase (InhA) and Mycobacterium tuberculosis.
AB  - In an effort to produce new lead antimycobacterial compounds, herein we have
      reported the synthesis of a sequence of new pyrrolyl benzamide derivatives. The
      new chemical entities were screened to target enoyl-ACP reductase enzyme, which
      is one of the key enzymes of M. tuberculosis that are involved in type II fatty
      acid biosynthetic pathway. Compound 3q exhibited H-bonding interactions with
      Tyr158, Thr196 and co-factor NAD+ that binds the active site of InhA. All the
      pyrrolyl benzamide compounds were evaluated as inhibitors of M. tuberculosis
      H37Rv as well as inhibitors of InhA. Among them, few representative compounds
      were tested for mammalian cell toxicity on the human lung cancer cell-line (A549)
      and MV cell line that presented no cytotoxicity. Five of these compounds
      exhibited a good activity against InhA.

PMID- 30223150
TI  - Bioactive seco-abietane rearranged diterpenoids from the aerial parts of Salvia
      prionitis.
AB  - Five previously undescribed 4,5-seco-abietane rearrange diterpenoids (1-5,
      Prionidipene A-E) were isolated from the aerial parts of Salvia prionitis, along
      with thirteen known seco-abietane diterpenoids (6-18). The structures of 1-5 were
      elucidated mainly based on analysis of NMR and MS data. The absolute
      configurations of 1-3 were determined by evaluation of experimental and
      calculated electronic circular dichroism (ECD) spectra. Putative biosynthetic
      pathways toward the formation of 1 and 2 are proposed. The nitric oxide (NO)
      production inhibitory effects of all isolates in lipopolysaccharide (LPS)-induced
      in RAW 264.7 cells were evaluated. Interestingly, compounds 4 and 9 with a furan
      ring showed potent inhibitory activity with IC50 values of 14.56 and 15.11 MUM,
      respectively.

PMID- 30223151
TI  - Medication administration by caregiving youth: An inside look at how adolescents
      manage medications for family members.
AB  - INTRODUCTION: Children take on the role of family caregiver throughout the world.
      No prior published research exists surrounding the particular circumstances of
      the task of medication administration and management by these youth, which was
      explored in this study. METHODS: A series of focus groups were conducted using
      semi-structured interviews of 28 previously identified caregiving youth ages 12
      19 years old who live in the United States. Data analysis followed guidelines of
      conventional content analysis. RESULTS: The following categories emerged about
      youth caregivers handling medications: 1) tasks involve organizational and
      administrative responsibilities; 2) youth have varying degrees of knowledge
      pertaining to these medications; 3) most share responsibility with other family
      members; 4) they lack formal education about their responsibilities; 5) multiple
      challenges exist relating to this task; 6) managing medications is associated
      with emotional responses; and 7) possible safety issues exist. CONCLUSIONS: These
      responsibilities represent a unique hardship and merit support and research from
      the medical, healthcare, legislative, and public health communities, among
      others.

PMID- 30223152
TI  - Does US expectancy mediate the additive effects of CS-US pairings on contingency
      instructions? Results from subjective, psychophysiological and neural measures.
AB  - Verbal instructions are a powerful pathway to learn new fear relations, and an
      important question has been what fear experience can still add to the effect of
      such instructions. Therefore, in previous studies, we investigated the effects of
      pairings between conditioned stimuli (CS) and unconditioned stimuli (US) after CS
      US contingency instructions. Although these studies found that CS-US pairings do
      indeed add to the effects of contingency instructions on subjective,
      psychophysiological and neural measures of conditioned fear, they also produce
      increases in US expectancy ratings. In the current report we address whether
      these enhanced US expectancy ratings can account for the additive effects of CS
      US pairings as suggested by expectancy models of fear conditioning. To address
      this question we made use of pathway models to investigate mediation in within
      subjects designs. Our results demonstrate that US expectancy ratings do not
      mediate the effects of CS-US pairings on fear ratings, the startle reflex or
      amygdala activation pattern similarity. Additional exploratory analyses, however,
      revealed that subjective fear ratings do explain the effects of CS-US pairings on
      the other measures. We discuss how these results relate to expectancy models of
      fear conditioning and what they implicate for the validity of US expectancy and
      fear ratings.

PMID- 30223153
TI  - The Karger vs bi-exponential model: Theoretical insights and experimental
      validations.
AB  - We revise three common models accounting for water exchange in pulsed-gradient
      spin-echo measurements: a bi-exponential model with time-dependent water
      fractions, the Karger model, and a modified Karger model designed for restricted
      diffusion, e.g. inside cells. The three models are compared and applied to
      experimental data from yeast cell suspensions. The Karger model and the modified
      Karger model yield very close results and accurately fit the data. The bi
      exponential model, although less rigorous, has a natural physical interpretation
      and suggests a new experimental modality to estimate the water exchange time.

PMID- 30223154
TI  - Capturing exchange using periodic radiofrequency irradiation.
AB  - The dynamics of spin system coupled by chemical exchange between two sites with
      different chemical shifts during periodic radiofrequency (RF) irradiation was
      here investigated. When the instantaneous pi-flip of effective frequency during
      the course of frequency sweep was applied, a significant increase of exchange
      induced relaxation rate constants was observed for small tip angle of
      magnetization in the laboratory frame of reference. This increase of the rate
      constants corresponds to the side bands generated by the periodic irradiation
      during the RF pulses. The exchange - induced relaxation rate constants depend on
      the exchange conditions, the RF power and the irradiation period. The described
      phenomenon promises applications for studying protein dynamics and for generating
      exchange specific relaxation contrasts in MRI.

PMID- 30223155
TI  - Long-range heteronuclear J-coupling constants in esters: Implications for 13C
      metabolic MRI by side-arm parahydrogen-induced polarization.
AB  - Side-arm parahydrogen induced polarization (PHIP-SAH) presents a cost-effective
      method for hyperpolarization of 13C metabolites (e.g. acetate, pyruvate) for
      metabolic MRI. The timing and efficiency of typical spin order transfer methods
      including magnetic field cycling and tailored RF pulse sequences crucially
      depends on the heteronuclear J coupling network between nascent parahydrogen
      protons and 13C, post-parahydrogenation of the target compound. In this work,
      heteronuclear nJHC (1 < n <= 5) couplings of acetate and pyruvate esters
      pertinent for PHIP-SAH were investigated experimentally using selective HSQMBC
      based pulse sequences and numerically using DFT simulations. The CLIP-HSQMBC
      technique was used to quantify 2/3-bond JHC couplings, and 4/5-bond JHC ? 0.5 Hz
      were estimated by the sel-HSQMBC-TOCSY approach. Experimental and numerical (DFT
      simulated) nJHC couplings were strongly correlated (P < 0.001). Implications for
      13C hyperpolarization by magnetic field cycling, and PH-INEPT and ESOTHERIC type
      spin order transfer methods for PHIP-SAH were assessed, and the influence of
      direct nascent parahydrogen proton to 13C coupling when compared with indirect
      homonuclear TOCSY-type transfer through intermediate (non-nascent parahydrogen)
      protons was studied by the density matrix approach.

PMID- 30223156
TI  - Development of a novel anoxic/oxic fed-batch membrane bioreactor (AFMBR) based on
      gravity-driven and partial aeration modes: A pilot scale study.
AB  - A novel pilot gravity-driven anoxic/oxic fed-batch membrane bioreactor (AFMBR)
      was developed to treat real domestic wastewater. In this process, the anoxic and
      oxic stages created favorable conditions for stable and continuous nitritation
      denitritation/denitrification-nitrification links without adding external carbon
      source. Excellent removals of organic carbon/nitrogen (NH4+-N: 71-97%, COD: 78
      96%, UV254: 70-95%, TN: 20-60%) and spontaneous permeability recovery were
      achieved simultaneously. It was assessed at micro levels by characterizing sludge
      particle morphologies, microbiota functional evolutions, fouling layer properties
      and energy consumptions. It was demonstrated that the aerobic granular sludge
      (AGS) was cultivated successfully. Notable differences of microbial diversity
      were observed in different regions of AFMBR. The SEM and AFM spectra suggested
      the loose cake layers can shed automatically due to low pressure and continue
      flushing. The energy consumption in AFMBR was around 0.042 kWh/m3, far lower than
      that of conventional MBR. Overall, the AFMBR has a potential on improvement of
      domestic wastewater treatment.

PMID- 30223157
TI  - Production, purification, characterization and application of a new halotolerant
      and thermostable endoglucanase of Botrytis ricini URM 5627.
AB  - A halotolerant endoglucanase with a molecular mass of 39 kDa was obtained from
      the solid fermentation of sugarcane bagasse by the fungus Botrytis ricini URM
      5627 and isolated using only two purification processes: fractionation with
      ammonium sulphate and size-exclusion chromatography resulting in an activity of
      1289.83 U/mL. After the isolation, biochemical characterizations were performed,
      giving a temperature of 50  degrees C and optimum pH of 5. The enzyme was stable
      at 39-60  degrees C for 60 min and at a pH of 4-6. The enzymatic activity
      increased in the presence of Na+, Mn2+, Mg2+ and Zn2+ and decreased in the
      presence of Ca2+, Cu2+, and Fe2+. The endoglucanase revealed a halotolerant
      profile since its activity increased proportionally to an increase in NaCl
      concentration. The maximum activity was reached at 2 M NaCl with a 75% increase
      in activity. The enzyme had a Km of 0.1299 +/- 0.0096 mg/mL and a Vmax of 0.097
      +/- 0.00121 mol/min/mL. During application in saccharification tests, the enzyme
      was able to hydrolyse sugarcane bagasse, rice husk, and wheat bran, with the
      highest production of reducers/fermentable sugars within 24 h of saccharification
      for wheat bran (137.21 mg/g). Therefore, these properties combined make this
      isolated enzyme a potential candidate for biotechnological and industrial
      applications.

PMID- 30223158
TI  - Effect of ball-milling on crystallinity index, degree of polymerization and
      thermal stability of cellulose.
AB  - A combined study of crystallinity index (CI), degree of polymerisation (DP) and
      thermal stability of cellulose was carried out for monitoring the effect of ball
      milling. DP and CI are two fundamental quantities that describe the physico
      chemical behaviour of cellulose. Milling is a common strategy to reduce cellulose
      crystallinity. In this work, four different commercially available celluloses
      were milled at 30, 60 and 120 min, and the changes in DP and CI were monitored
      using spectroscopic, diffraction and chromatographic techniques. Evolved gas
      analysis-mass spectrometry (EGA-MS) was also used to evaluate the changes in
      apparent activation energy (Ea) of the pyrolysis reaction upon different milling
      times by using model-free isoconversional methods. The results showed substantial
      decrease in CI values and moderate changes in DP after two-hours of ball-milling.
      Ea were found in the range 110-140 kJ/mol, and were reduced by 10% on average
      after two hours of ball-milling.

PMID- 30223159
TI  - Key environmental factors to variation of ammonia-oxidizing archaea community and
      potential ammonia oxidation rate during agricultural waste composting.
AB  - In this research, the abundance and structure of AOA amoA gene during
      agricultural waste composting were determined by quantitative PCR and sequencing
      techniques, respectively. Pairwise correlations between potential ammonia
      oxidation (PAO) rate, physicochemical parameters and the AOA abundance were
      evaluated using Pearson correlation coefficient. Relationships between these
      parameters, PAO rates and AOA community structure were evaluated by redundancy
      analysis. Results showed that 22 AOA gene OTUs were divided into the
      soil/sediment lineage by phylogenetic analyses. Significant positive correlations
      were obtained between AOA amoA gene abundance and moisture, ammonium, water
      soluble carbon (WSC) and organic matter (OM), respectively. Redundancy analysis
      showed OM, pH and nitrate significantly explained the AOA amoA gene structure.
      Pearson correlation revealed the PAO rate correlated positively to ammonium, AOA
      amoA gene abundance. These results indicated that AOA communities sense the
      fluctuations in surrounding environment, and ultimately react and influence the
      nitrogen transformation during agricultural waste composting.

PMID- 30223160
TI  - Economic burden of obesity and four obesity-related chronic diseases in rural
      Yunnan Province, China.
AB  - OBJECTIVE: To analyze the economic burden of obesity and four obesity-related
      chronic diseases in rural Yunnan Province, China. STUDY DESIGN: A community
      based, cross-sectional study was conducted among rural residents in Yunnan
      Province. A multistage stratified random sampling approach was applied to collect
      a sample of the population aged >=35 years in this region. METHODS:
      Questionnaires were conducted and measurements were taken from 5040 participants.
      A two-step model was used to measure direct economic burden of disease, whereas a
      human capital approach was applied to measure indirect economic burden. RESULTS:
      The prevalence of general obesity, central obesity, hypertension, diabetes,
      coronary heart disease, and stroke was 7.1%, 37.0%, 35.3%, 9.9%, 3.8%, and 1.7%,
      respectively, while obese participants as expected had a higher risk of the
      aforementioned four obesity-related illnesses than their counterparts (P < 0.01).
      The total, direct, and indirect costs of the four illnesses were $30,350.8
      million, $28,642.5 million, and $1708.3 million, respectively, with 12.7%
      attributable to general obesity and 28.7% attributable to central obesity.
      CONCLUSIONS: The economic burden of the four studied chronic diseases
      attributable to obesity in rural Yunnan Province is substantial. Interventions
      for controlling obesity should be applied to prevent obesity-related diseases and
      reduce the economic burden of disease.

PMID- 30223161
TI  - Mirror exposure therapy for body image disturbances and eating disorders: A
      review.
AB  - Mirror exposure therapy is a clinical trial validated treatment component that
      improves body image and body satisfaction. Mirror exposure therapy has been shown
      to benefit individuals with high body dissatisfaction and patients with eating
      disorders (ED) in clinical trials. Mirror exposure is an optional component of
      cognitive behavioral therapy (CBT), an effective treatment for body dysmorphic
      disorder (BDD). However, most clinical trials of mirror exposure therapy have
      been small or uncontrolled and have included few male subjects. Adverse events
      have been reported during mirror exposure clinical trials. We discuss how
      individuals respond when looking in a mirror and how mirrors can be used
      therapeutically, and we critically evaluate the evidence in favor of mirror
      exposure therapy. We discuss clinical indications and technical considerations
      for the use of mirror exposure therapy.

PMID- 30223162
TI  - Summer-winter differences of PM2.5 toxicity to human alveolar epithelial cells
      (A549) and the roles of transition metals.
AB  - Atmospheric fine particulate matters (PM2.5) induce adverse human health effects
      through inhalation, and the harmful effects of PM2.5 are determined not only by
      its air concentrations, but also by the particle components varied temporally. To
      investigate seasonal differences of the aerosol toxicity effects including cell
      viability and membrane damage, cell oxidative stress and responses of
      inflammatory cytokines, the human lung epithelial cells (A549) were exposed to
      PM2.5 samples collected in both summer and winter by the in vitro toxicity
      bioassays. Toxicological results showed that, the PM2.5 led to the cell viability
      decrease, cell membrane injury, oxidative stress level increase and inflammatory
      responses in a dose-dependent manner. Temporally, the cytotoxicity of winter
      PM2.5 was higher than summer of this studied industrial area of Nanjing, China.
      According to the different contents of heavy metals accumulated in PM2.5, the
      transition metals such as Cu might be an important contributor to the aerosol
      cell toxicity.

PMID- 30223163
TI  - Effectiveness of simultaneous applications of lime and zinc/iron foliar sprays to
      minimize cadmium accumulation in rice.
AB  - Due to the large area of Cd-contaminated paddy soils worldwide, low-cost measures
      to reduce the accumulation of Cd in rice plant are necessary. A field experiment
      was therefore conducted to investigate the reducing effect of lime combined with
      foliar applications of Zn (ZnSO4) or Fe (EDTA.Na2Fe) on Cd concentrations in
      brown rice on a Cd-contaminated paddy soil. The results indicated that liming
      alone or in combination with foliar sprays of Zn or Fe increased the soil pH by
      0.27-0.63 units. However, limited effects of lime or lime combined with foliar
      applications of Zn/Fe on soil DTPA-extractable Cd, rice grain and rice straw
      biomass were observed. Liming alone significantly reduced the Cd concentration in
      brown rice and rice straw by 31.8% and 42.3%, respectively. The Cd concentrations
      in brown rice decreased by 25.5% and 65.4% and in rice straw by 53.0% and 68.1%
      after liming combined with foliar applications of Fe and Zn, respectively. In
      contrast, liming combined with foliar spraying of Fe significantly increased the
      transfer ratio of Cd from the rice straw to the grain. As a low-cost technique,
      lime application combined with foliar application of ZnSO4 could be recommended
      for the remediation of Cd-contaminated paddy soils.

PMID- 30223164
TI  - Tellurite biotransformation and detoxification by Shewanella baltica with
      simultaneous synthesis of tellurium nanorods exhibiting photo-catalytic and anti
      biofilm activity.
AB  - Tellurite reducing bacterial strain was isolated from Zuari estuary, Goa India
      which could tolerate 5.5 mM potassium tellurite with a minimum inhibitory
      concentration of 6 mM. This strain was designated as GUSDZ9 and was identified as
      Shewanella baltica (accession number: MF350629) based on 16S rRNA gene sequencing
      and BLAST analysis. The Diethyl-dithiocarbamate based colorimetric analysis
      clearly demonstrated a complete reduction of 2 mM tellurite to elemental
      tellurium during the late stationary phase. Te Nanoparticles (TeNPs) biosynthesis
      which initiated at early log phase (i.e. 4 h) was evidently monitored through
      colour change and a peak due to surface plasmon resonance at 210 nm using UV-Vis
      spectroscopic analysis. X-ray crystallographic studies and transmission electron
      microscopy revealed unique nano-rods with a diameter ranging from 8 to 75 nm.
      Energy dispersive X-ray analysis further confirmed the presence of pure
      tellurium. The biogenic TeNPs at 10 and 5 ug/mL evidently demonstrated 90%
      degradation of methylene blue dye and anti-biofilm activity against potential
      Gram-positive and Gram-negative human pathogens respectively. The alkaline comet
      assay revealed time and dose-dependent genotoxicity at concentrations higher than
      15 ug/mL of TeNPs. This study clearly demonstrated the potential of Shewanella
      baltica strain GUSDZ9 in bioremediation of toxic tellurite through bio-reduction
      into elemental tellurium and involvement of biogenic TeNPs in the photo-catalytic
      reduction of methylene blue and anti-biofilm activity. This is the first report
      of its kind on the synthesis of biogenic TeNPs from Shewanella baltica
      demonstrating photo-catalytic, anti-biofilm activity as well as genotoxicity.

PMID- 30223165
TI  - Integrating bioavailability and soil aging in the derivation of DDT criteria for
      agricultural soils using crop species sensitivity distributions.
AB  - Although the agricultural use of dichlorodiphenyltrichloroethane (DDT) has been
      banned for decades in many countries around the world, the detection of DDT and
      its metabolites in soils is very common due to their persistence. DDTs (sum of
      DDT and its metabolites) in farmland soils can be absorbed by crops at different
      levels and accumulate in the edible parts of agricultural products, posing
      threats to the health of human being. However, no information on the species
      sensitivity distribution (SSD) of crops with regard to DDTs has been reported due
      to the lack of enough bioavailability data and models to normalize the
      bioavailability data from different sources. Based on the bioconcentration
      factors of 17 crop species in Chinese soils obtained from previous studies, the
      criteria of DDTs in soils was derived according to the quality standard of
      agricultural products using the SSD method. Corrections for water content and
      aging time were conducted to normalize the data from different sources. The risk
      values of agricultural products at different concentration levels of DDTs in
      soils were also evaluated. It was found that oil crops are able to take up more
      DDTs than non-oil crops, so the soil criteria were calculated separately for oil
      crops and non-oil crops, which were 0.083 mg/kg and 0.29 mg/kg, respectively.
      With the residual concentrations of DDTs in soils at the range of 0.01-0.5 mg/kg,
      0-8% of the agricultural products exceeded the permissible limits for DDTs which
      were set in the National Food Safety Standard of China. The results also
      demonstrated the feasibility for applying SSDs to derive the soil criteria of
      DDTs in order to ensure the safety of agricultural products. This work will
      provide information for the risk assessment and the establishment of soil
      environmental quality standards to ensure safe agricultural production.

PMID- 30223166
TI  - Adsorptive mercaptan removal of liquid phase using nanoporous graphene:
      Equilibrium, kinetic study and DFT calculations.
AB  - This research investigated the adsorption of tertiary butyl mercaptan (TBM) from
      liquid phases by using nanoporous graphene. Nanoporous graphene synthesized
      through chemical vapor deposition method was characterized using Brunauer-Emmett
      Teller method, transmission electron microscopy, field-emission scanning
      microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy
      techniques. The TBM adsorption equilibrium was investigated by using Langmuir,
      Freundlich, and Tempkin models. The obtained results were in good agreement with
      the Freundlich isotherm. The adsorption kinetics of this process was modeled by
      the pseudo-first-order, pseudo-second-order, and intraparticle models. The
      adsorption rate was obtained according to the pseudo-second-order model. The
      satisfactory results indicated that nanoporous graphene can be used as a good
      carbon nanostructure sorbent in mercaptan removal. The process reduced the sulfur
      content from 300 ppm to less than 10 ppm which was the standard level in
      environmental regulations. The capacity for TBM removal was achieved at 4.4 gr
      S/gr adsorbent. The desulfurization efficiency was revealed about 96.3% for
      nanoporous graphene at 298 K and 24 h. Moreover, density functional theory
      calculations were used to determine the stable configuration, adsorption energy,
      and electronic structure of different configurations of TBM adsorbed onto a
      graphene surface. TBM physically adsorbed onto the graphene surface with
      adsorption energies of approximately - 25 kJ/mol was indicated from DFT
      calculations.

PMID- 30223167
TI  - Spatial distribution, accumulation and human health risk assessment of heavy
      metals in soil and groundwater of the Tano Basin, Ghana.
AB  - Soil serves as a vast matrix for heavy metal accumulation and subsequent
      redistribution to critical aspects of the environment such as groundwater. Soil
      pollution study is essential for sustainable human health and ecosystem
      protection. This study provides vital insight into the fate, accumulation,
      interactions, and health risk posed by heavy metals in soil and groundwater by
      employing geochemical accumulation index (Igeo), risk assessment models and
      multivariate data analysis techniques such as principal component analysis (PCA),
      preference ranking organisation method for enrichment evaluation (PROMETHEE) and
      geometrical analysis for interactive aid (GAIA). The median Igeo estimates show
      moderate to strong Pb accumulation levels whilst all the other metals indicate
      uncontaminated to moderate levels. The PCA output point to anthropogenic origin
      of Pb and Cd in the Tano Basin and surrounding communities. PROMETHEE-GAIA
      results indicate that Pb, Cd, Zn and Fe accumulated in the soil matrix may
      potentially leach into the groundwater resources. The carcinogenic lifetime risks
      posed by Pb, Cd, and Ni metals to adults are within the tolerable acceptable risk
      and thus do not present an immediate danger in the study area. Due to the
      significant toxicity, bioaccumulation and biomagnification properties of Pb and
      Cd in the environment, areas associated with significant anthropogenic activities
      require regular monitoring and evaluation in order to ensure that these metals
      are consistently below the regulatory limits. This study has further elucidated
      the subject of heavy metal pollution and is therefore expected to enhance
      sustainable protection of the environment and human health.

PMID- 30223168
TI  - Comparative effects of nano and bulk-Fe3O4 on the growth of cucumber (Cucumis
      sativus).
AB  - Cucumber (Cucumis sativus) plants were cultivated in hydroponic media with nano
      and bulk- iron oxide (Fe3O4) (50, 500 and 2000 mg/L) over a period of 21 days. At
      the low concentration (50 mg/L), nano-Fe3O4 resulted in reduction of biomass and
      enzyme activities compared to the control. However, at the higher concentration
      of nano-Fe3O4 dosage (2000 mg/L), there was a significant increase in biomass,
      antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD). In contrary,
      the high concentration of bulk-Fe3O4 caused phytotoxicity in terms of biomass and
      enzymes activity. The phytotoxicity was dependent on the particles property
      (mainly sizes and aggregation) for nano-F3O4 and concentration dependent for bulk
      Fe3O4. The particle size is an important factor that can influence the
      bioavailability of nanomaterials, which need to be included when evaluating the
      exposure of nanomaterials and their deleterious effects in the environment. These
      promising results can help to develop the possible application of Fe3O4 NPs which
      may improve nutrient management to overcome food security.

PMID- 30223169
TI  - Challenge Based Learning nurtures creative thinking: An evaluative study.
AB  - BACKGROUND: The demand for more creative and innovative nurses and together with
      the rapid expansion of nurse education in Mainland China have called for new
      approaches to student learning. Challenge Based Learning, an active student
      directed approach was incorporated into an elective course in an undergraduate
      nursing programme. Initially, the students were given some big ideas about the
      real world. They worked together in small groups to identify the most challenging
      problems from these ideas, develop some innovative solutions, formulate an action
      plan for a selected solution, carry out the actions and evaluate the outcome.
      OBJECTIVES: To evaluate the effectiveness of Challenge Based Learning on
      students' creativity and innovativeness. DESIGN: Quasi-experimental. SETTINGS: A
      medical university in Guangzhou, China. METHOD AND PARTICIPANTS: A convenience
      sample of 48 undergraduate nursing students from the bilingual class, who
      enrolled in the elective course, Innovation and Creative Thinking was invited to
      participate in the evaluative study. They completed the Creativity and Innovation
      Effectiveness Profile before and after the course. RESULTS: Apart from
      descriptive statistics, the mean scores of the Creativity and Innovation
      Effectiveness Profile between the pretest and posttest assessments were analyzed
      using the Wilcoxon signed ranks test. The results showed that the mean scores of
      all 7 domains (i.e. creative consciousness, levels of curiosity, pattern breaking
      skills, idea nurturing ability, willingness to experiment and take risks, courage
      and resilience and energetic persistence) of Creativity and Innovation
      Effectiveness were significantly higher in the posttest. CONCLUSION: Students can
      enhance their ability to innovate and create through learning. The successful
      practical experience of using CBL in the study provides a good reference for
      nurse teachers who want their students to be self-directed, creative and
      innovative.

PMID- 30223170
TI  - Ictal asystole: A rare phenomenon in neauroanesthesia.

PMID- 30223171
TI  - A comparison of systemic and local dexamethasone administration: From
      perilymph/cochlea concentration to cochlear distribution.
AB  - Different types of inner ear diseases can damage different cochlear subsites by
      different mechanisms. Steroids administered by different methods are commonly
      used for treating inner ear diseases. There is reason to believe that
      dexamethasone (Dex) may reach cochlear subsite targets via different pathways
      after administration by different methods: Intratympanic (IT), postaural (PA),
      and intraperitoneal (IP). The purpose of this study was to explore the cochlear
      concentration and distribution of Dex after administration by different methods.
      High-performance liquid chromatography-mass spectrometry and immunofluorescence
      technology were employed to measure and compare the Dex concentration in the
      perilymph and cochlear tissue and the cochlear distribution of Dex. IT
      administration resulted in higher Dex concentrations in the perilymph and
      cochlear tissues than those with the other administration methods. Intratympanic
      and postaural administration could result in higher Dex concentrations in the
      organ of Corti than systemic administration, but systemic administration could
      result in higher Dex concentrations in the stria vascularis than the other
      administration methods. A decreasing basal-apical gradient of Dex uptake was
      present in the cochlea after IT but not IP or PA administration. These results
      indicate that different administration methods result in different Dex
      distributions, which can be attributed to features of the cochlear vascular
      system and intracochlear diffusion. Our results provide clinicians with an
      experimental basis for the use of different steroid injection routes to optimize
      the effects on inner ear diseases with different target organs.

PMID- 30223172
TI  - Vector-transmission of plant viruses and constraints imposed by virus-vector
      interactions.
AB  - Because plants are sessile and their cells protected by a cell wall, the contact
      transmission of plant viruses is very rare. Almost all plant viruses are
      transmitted by vectors, which can be insects, nematodes, mites or fungi. Although
      very efficient, this mode of transmission is not trivial and imposes numerous
      constraints on viruses. In this review we show that these constraints apply at
      all stages of the transmission process and at all scales, from the molecular to
      ecological interactions. We discuss several viral adaptations that likely reflect
      sophisticated means to alleviate these constraints and to maximize transmission,
      and we point at gaps and future directions in this field of research.

PMID- 30223173
TI  - Evaluation capacity building-Results and reflections across two years of a
      multisite empowerment evaluation in an HIV prevention context.
AB  - As the need for rigorous evidence of program efficacy increases, integrating
      evaluation activities into program implementation is becoming crucial. As a
      result, external evaluators are placing increased focus on evaluation capacity
      building as a practice. However, empirical evidence of how to foster evaluation
      capacity in different contexts remains limited. This study presents findings from
      an evaluation capacity survey conducted within a multisite Empowerment Evaluation
      initiative, in which an external evaluator worked with 20 project teams at
      diverse community agencies implementing HIV prevention projects. Survey results
      revealed representatives from project teams (n = 33) reported significantly
      higher overall evaluation capacity after engaging with the external evaluator on
      planning and implementing their evaluation. Improvements differed across
      organization type, intervention type, staff position, and reported engagement on
      various activities throughout the course of the evaluation. Results indicated
      empowerment evaluation and other stakeholder-focused evaluation approaches are
      broadly applicable when evaluation capacity building is a desired outcome,
      particularly when able to engage project staff in the planning of the evaluation
      and in delivering technical assistance services. Accordingly, efforts should be
      made by program funders, staff, and evaluators to encourage active engagement
      starting in the early stages of program and evaluation planning.

PMID- 30223174
TI  - Inequality and health among foreign-born latinos in rural borderland communities.
AB  - Thousands of Mexicans and Central Americans settle in communities along the
      borderlands between Mexico and the United States. Many live and work in rural
      communities characterized by poverty and limited access to basic resources.
      Drawing on qualitative research, this article reports on inequalities and health
      among foreign-born Latinos in rural borderland communities. From 2015 to 2016,
      the study team conducted research in Inland Southern California's Eastern
      Coachella Valley with Mexican farmworkers, farmworker advocates, community
      leaders, healthcare service providers, and local political leaders. The analysis
      of field notes and interviews demonstrates how situational and temporal factors
      position this foreign-born population as vulnerable to inequalities across
      multiple social systems resulting in low social status, lack of employment and
      housing stability, and limited access to healthcare services. Over time, the
      experience of both situational life events and persistent and daily chronic
      strain infringes on self-concept, including mastery or control over life and self
      worth, and contributes to stress and subsequent poor mental health outcomes
      (e.g., depression). The research calls for local community action, healthcare
      policy change, and further in-depth research on structural inequalities in health
      among foreign-born Latinos.

PMID- 30223175
TI  - Management and birth outcomes of pregnant women with Chiari malformations: A 14
      years retrospective case series.
AB  - OBJECTIVE: The management of Chiari malformations in pregnancy is challenging due
      to the perceived risk of adverse maternal neurological outcomes and raising
      intracranial pressure during labour. Our aim was to evaluate the management and
      health outcomes of pregnant women cared for at a regional referral centre and
      highlight elements of best practice. STUDY DESIGN: A retrospective case series of
      all pregnant women diagnosed with Chiari malformation over fourteen years
      (January 2004-June 2018) at the Birmingham Women's Hospital - UK. RESULTS: Twenty
      one women (23 pregnancies) with Chiari malformation were included, four had
      syringomyelia (4/21,19%) and six had previously undergone craniovertebral
      decompression (6/21, 29%). The median age was 34-years (range 20-41), the median
      gravidity was two (range 1-8), the median parity was one (range 0-6), and the
      median extent of tonsillar herniation was 11 mm (range 9-18). The majority of
      women received their preferred mode of delivery (15 normal vaginal deliveries
      (15/23, 65.2%) and 6 elective Caesarean sections (6/23, 26.1%)) with two
      pregnancies ending with an emergency caesarean section for obstetric
      complications (2/23, 8.7%). Five Caesarean section were performed under general
      anaesthetic, two under spinal (2/23, 8.7%) and one under epidural anaesthesia
      (1/23, 4.3%) with no neurological sequelae. There were no adverse neurological
      outcomes at discharge postnatally. CONCLUSIONS: Offering normal vaginal delivery
      with effective analgesia, for women with Chiari malformation, appears to be safe.
      Pregnancy care should be provided by a multi-disciplinary team with experience in
      managing Chiari malformation.

PMID- 30223176
TI  - Measuring the violence prevention climate: Development and evaluation of the VPC
      14.
AB  - BACKGROUND: Violence and aggression are common in inpatient mental health
      hospital settings and cause problems for staff, patients and organisations. An
      important factor in treatment efficacy is ward atmosphere, and one element of
      this is the violence prevention climate. OBJECTIVES: To develop and test the
      psychometric properties of a new scale to measure perceptions of the violence
      prevention climate among staff and patients in mental health inpatient settings.
      DESIGN: Scale development and cross-sectional validation study. SETTING AND
      PARTICIPANTS: Three hospital sites within an independent sector provider of
      secure mental health care. Participants were patients and staff residing
      in/working on wards in the adult male and female mental health care pathways.
      METHODS: The study was conducted in three stages: scale development, pilot
      testing and psychometric evaluation. The scale items were developed from
      systematic literature review, informant interviews (staff) and focus groups
      (patients) and expert review. The resulting scale was subject to pilot testing
      with staff and patients (n = 58 and n = 25). The reliability and validity of the
      scale was examined by administering it to 326 staff and 95 patients. Exploratory
      factor analysis was used to establish construct validity, and this was further
      assessed with Rasch modelling. Internal consistency was assessed by calculation
      of Cronbach's alpha coefficients. Convergent and discriminant validity were
      measured by comparing results with existing validated instruments. Temporal
      stability of the items was assessed using test-retest reliability coefficients.
      RESULTS: The VPC-14 is a 14-item scale demonstrating good psychometric
      properties. Exploratory factor analysis revealed two subscales, staff actions and
      patient actions, each demonstrating good internal consistency (Cronbach's alpha
      .89 and .76). All items demonstrated good temporal stability. Rasch modelling
      confirmed the unidimensionality of the two subscales, and items demonstrated high
      construct validity. Moderate correlations were found between subscales of the VPC
      14 and the EssenCES, whilst no correlations were found with items in the ACMQ,
      thus demonstrating good convergent and discriminant validity. CONCLUSION: The VPC
      14 is currently the most robust available measure of the inpatient violence
      prevention climate. It is quick and easy to administer, considers views of both
      staff and patients and thus can be introduced as standard practice in a ward
      setting. Potential uses include tracking the violence prevention climate
      longitudinally and in evaluation of new policy and procedural interventions.

PMID- 30223177
TI  - Phase transition and hardness evolution of a Ti-5Al-5Mo-1Fe-1Cr alloy subjected
      to isothermal aging.
AB  - In this paper, a Ti-5Al-5Mo-1Fe-1Cr alloy was isothermally aged at 500  degrees C
      for different periods. Phase transformation took place during the aging
      treatment. The phase transformation was studied by X-ray diffraction spectroscopy
      and transmission electron microscopy. The as-quenched sample was composed of
      matrix beta (body-centered cubic structure) phase, omegaath (hexagonal structure)
      phase and minor alpha (hexagonal close-packed structure) phase. The results
      showed that aging treatment promoted the beta -> omega -> alpha phase
      transformations in the as-quenched alloys. Different isothermal aging time
      affected the contents and morphologies of the three phases inside the alloy and
      thus the hardness. It was found that the content of hard omega phase plays an
      important role in the hardness of the Ti-5Al-5Mo-1Fe-1Cr alloy. The hardness of
      alloy showed an overall decreasing trend as the aging time increased to 2 h,
      except for the temporary slight increase of the hardness at an aging time of 1 h.

PMID- 30223178
TI  - Evaluation of the effectiveness of conservation practices under implementation
      site uncertainty.
AB  - Agricultural nonpoint source pollution is the leading source of water quality
      degradation in United States, which has led to the development of programs that
      aim to mitigate this pollution. One common approach to mitigating nonpoint source
      pollution is the use of best management practices (BMPs). However, it can be
      challenging to evaluate the effectiveness of implemented BMPs due to polices that
      limit data sharing. In this study, the uncertainty introduced by data sharing
      limitations is quantified through the use of a watershed model. Results indicated
      that BMP implementation improved the overall water quality in the region (up to
      ~15% pollution reduction) and that increasing the area of BMP implementation
      resulted in higher pollution reduction. However, the model outputs also indicated
      that uncertainty caused by data sharing limitations resulted in variabilities
      ranging from -160% to 140%. This shows the importance of data sharing among
      agencies to better guide current and future conservation programs.

PMID- 30223179
TI  - The role of the operating parameters of SBR systems on the SMP production and on
      membrane fouling reduction.
AB  - In this work, six identical laboratory SBRs treating simulated wastewater were
      operated in parallel studying the effect of three food-to-microorganisms ratio
      (F/M ratio; 0.20, 0.35 and 0.50 kg COD.kg MLSS-1.d-1), two hydraulic retention
      times (HRT; 24 and 16 h) and two values of number of cycles per day (3 and 6).
      Influence of these operational parameters on the SMPs production and reactor
      performance, were studied. Results indicated that the highest F/M ratio, HRT and
      cycles/day produced 72.7% more of SMP. In a second experimental series,
      biological process yielding the maximal and the minimal SMPs production were
      replicated and both mixed liquors (ML) and treated effluents were ultrafiltrated.
      The flux decay in the conditions of minimum and maximum SMPs production were 52%
      and 72%, when the SBRs effluents were ultrafiltrated while no significant
      differences in the ultrafiltration of ML were found. In terms of permeability
      recovery, this was lower for the case of the ML (73% and 49% of initial
      permeability recovered for effluent and ML ultrafiltration, respectively).

PMID- 30223180
TI  - Water-soluble polymeric xenobiotics - Polyvinyl alcohol and polyvinylpyrrolidon -
      And potential solutions to environmental issues: A brief review.
AB  - This paper describes a potential environmental problem closely linked with the
      global production of water-soluble polymers such as polyvinyl alcohol (PVA) and
      polyvinylpyrrolidone (PVP). Both polymers make up the components of a multitude
      of products commonly utilized by industries and households. Hence, such a
      widespread use of PVA and PVP in the industrial sector and among consumers (the
      concentration of PVP in urban wastewater is approximately 7 mg/L) could pose a
      considerable problem, particularly to the environment. To this end, many
      publications have recently highlighted the poor biodegradability of PVA, in
      principle influenced by numerous biotic and abiotic factors. Facts published on
      the environmental fate of PVP have been scant, basically reporting that it is a
      biologically resistant polymer. As a result, the commercially produced water
      soluble polymers of PVA and PVP are essentially non-biodegradable and possess the
      capacity to accumulate in virtually all environmental media. Consequently, there
      is a chance of heightened risk to the very environmental constituents in which
      PVA and PVP accumulate, depending on the routes of entry and transformation
      processes underway in such constituents of the ecosystem. This assumption is
      confirmed by the findings of initial research, which is worrying. Herein, PVA was
      detected in a soil environment, while a relatively high concentration of PVP was
      found in river water. A review of the literature was conducted to summarize the
      current state of knowledge concerning the fate of PVA and PVP in various
      environments, thereby also discerning potential solutions to tackle such dangers.
      This paper proposes methods to enhance the biodegradability of materials
      containing such materials; for PVA this means utilizing a suitable
      polysaccharide, whereas for PVP this pertains to actuating applications that
      induce substances to degrade. Accordingly, while it is understandable that this
      work cannot fully address all the issues associated with polymeric xenobiotics,
      it can still serve as a guide to discerning an economically viable solution, and
      provide a foundation for further research.

PMID- 30223181
TI  - The gut-liver axis in hepatocarcinoma: a focus on the nuclear receptor FXR and
      the enterokine FGF19.
AB  - Elevated bile acid (BA) concentrations in the liver is associated with severe
      disease, including cholestasis and hepatocellular carcinoma. The nuclear
      Farnesoid X Receptor (FXR) is the master regulator of BAs homeostasis. In the
      ileum, BA-dependent FXR activation induces the production of the fibroblast
      growth factor FGF19, a hormone that reaches the liver through the portal system
      where it represses the expression of CYP7A1, the rate limiting enzyme in the
      process of hepatic BAs synthesis. This gut-liver FXR-FGF19 dual action is the
      paradigm of physiological BA regulation and it is currently targeted in the
      clinical practice for liver disease such as primary cholangitis. At a variance of
      FXR activation, native FGF19 has strong anti-cholestatic and anti-fibrotic
      activity in the liver but it retains peculiar pro-tumorigenic actions. Thus,
      novel analogues have been generated to avoid tumorigenic capacity while
      maintaining BA metabolic action. Here we present a novel and intriguing view on
      the putative possibility to target the FXR-FGF19 duo in order to offer a bona
      fide promising therapeutic approach to bile acid promoted hepatocarcinoma.

PMID- 30223182
TI  - Novel crAssphage marker genes ascertain sewage pollution in a recreational lake
      receiving urban stormwater runoff.
AB  - Considerable efforts have been made in recent years in developing novel marker
      genes for fecal pollution tracking in environmental waters. CrAssphage are
      recently discovered DNA bacteriophage that are highly abundant in human feces and
      untreated sewage. In this study, we evaluated the host-sensitivity and 
      specificity of the newly designed crAssphage qPCR assays (Stachler et al., 2017)
      CPQ_056 and CPQ_064 (i.e., marker genes) in fecal samples collected from various
      human and several animal host groups in Australia. We also investigated the
      utility of these marker genes to detect sewage pollution in an urban recreational
      lake (i.e., Lake Parramatta) in Sydney, NSW. The mean concentrations of CPQ_056
      and CPQ_064 marker genes in untreated sewage were 9.43 +/- 0.14 log10 GC/L and
      8.91 +/- 0.17 log10 GC/L, respectively, 2 to 3 orders of magnitude higher than
      other sewage-associated viruses used in microbial source tracking studies. Among
      177 animal fecal samples tested from 11 species, the host-specificity values for
      CPQ_056 and CPQ_064 marker genes were 0.95 and 0.93, respectively. Limited cross
      reactivity was observed with cat fecal and cattle wastewater samples. Abundance
      of crAssphage markers were monitored in an urban lake that receives stormwater
      runoff. The concentrations of both markers were higher (CPQ_056 ranging from 3.40
      to 6.04 log10 GC/L and CPQ_064 ranging from 2.90 to 5.47 log10 GC/L) in 20 of 20
      (for CPQ_056) and 18 of 20 (for CPQ_064) samples collected after storm events
      with gauged sewer overflows compared to dry weather event (10 of 10 samples were
      qPCR negative for the CPQ_056 and 8 of 10 were negative for the CPQ_064 marker
      genes) suggesting sewage pollution was transported by urban stormwater runoff to
      Lake Parramatta. The results of the study may provide context for management of
      sewage pollution from gauged overflow points of the sewerage system in the
      catchment.

PMID- 30223183
TI  - A case of sciatica revealing a giant syphilitic aneurysm.

PMID- 30223184
TI  - Implementation of the safewards model to reduce the use of coercive measures in
      adult psychiatric inpatient units: An interrupted time-series analysis.
AB  - The aim of this study was to investigate whether the implementation of the
      Safewards model reduces the frequency of coercive measures in adult psychiatric
      inpatient units. Data on all coercive measures performed in psychiatric hospitals
      in the Region of Southern Denmark 1/1/2012-31/3/2017 were collected
      retrospectively through The Register of Coercive Measures in Psychiatric
      Treatment. Interrupted time series analysis by segmented regressions with poisson
      models were performed on overall coercive measures (n = 12,660), mechanical
      restraint (n = 2948) and forced sedation (n = 4373). A 2% (95% CI: 1%-4%, p <
      0.001) decrease per quarter in the frequency of coercive measures and an 11% (95%
      CI: 8%-13%, p < 0.001) decrease per quarter in the frequency of forced sedation
      were found after the implementation of the Safewards model. In conclusion, the
      implementation of the Safewards model in adult psychiatric inpatient units was
      associated with a decrease in forced sedation and potentially the overall use of
      coercive measures.

PMID- 30223185
TI  - New cues for body axis formation in plant embryos.
AB  - Plant embryogenesis initiates with the fusion of sperm and egg cell, and
      completes the generation of the basic outline of the future plant. Here, we
      summarize the recent findings about the signaling cascade triggering the zygotic
      transcription, and the intracellular events and regulatory factors involved in
      the formation of the two major body axes. We highlight the lack of systematic de
      novo transcriptional activation in the zygote, and emphasize the importance of
      cytoskeletal reorganization to polarize the zygote and control the first
      asymmetric division that establishes the apical-basal axis. Finally, the limited
      knowledge of mechanisms that control the cell divisions separating the inner and
      outer cell layers is summarized and we propose approaches to enhance our
      understanding of basic principles of plant embryogenesis.

PMID- 30223186
TI  - Molecular cartography of leaf development - role of transcription factors.
AB  - Organ elaboration in plants occurs almost exclusively by an increase in cell
      number and size. Leaves, the planar lateral appendages of plants, are no
      exception. Forward and reverse genetic approaches have identified several genes
      whose role in leaf morphogenesis has been inferred from their primary effect on
      cell number and size, thereby distinguishing them as either promoters or
      inhibitors of cell proliferation and expansion. While such classification is
      useful in studying size control, a similar link between genes and shape
      generation is poorly understood. Computational modelling can provide a conceptual
      framework to re-evaluate the known genetic information and assign specific
      morphogenetic roles to the transcription factor-encoding genes. Here we discuss
      recent advances in our understanding of the roles of transcription factors in the
      planar growth of leaf lamina in two orthogonal dimensions.

PMID- 30223187
TI  - Nighttime media use in adolescents with ADHD: links to sleep problems and
      internalizing symptoms.
AB  - OBJECTIVE: This study examined nighttime media use in relation to sleep problems
      and anxiety/depression symptoms in adolescents with attention
      deficit/hyperactivity disorder (ADHD). METHODS: Participants were 81 adolescents
      (69% male) ages 13-17 with ADHD. Adolescents completed measures assessing
      pubertal development, nighttime media use, circadian preference, and daytime
      sleepiness. Both adolescents and parents completed measures of sleep duration,
      sleep problems, and internalizing symptoms. RESULTS: When summing across media
      uses (eg, social networking, playing video games, watching television), the
      average nighttime media use (after 9:00PM) was 5.31 h. Overall, 63% of
      adolescents reported obtaining less than 8 h of sleep on school nights, and this
      percentage rose to 77% for parent-reported sleep duration. Moreover, adolescents
      obtaining less sleep than recommended had more nighttime media use than those
      obtaining >=8 h of nightly sleep. Controlling for age, sex, pubertal development,
      stimulant medication use, and ADHD symptom severity; nighttime media use was
      associated with shorter sleep duration and increased sleep problems across both
      adolescent and parent report. Media use was also associated with greater
      adolescent-reported anxiety and depression, and marginally associated with
      eveningness circadian preference and greater daytime sleepiness. In considering
      specific anxiety dimensions, media use was associated with greater adolescent
      reported panic symptoms and parent-reported generalized anxiety disorder
      symptoms. CONCLUSIONS: Our findings suggest that nighttime media use may
      contribute to sleep problems and comorbid internalizing symptoms in adolescents
      with ADHD, although additional studies are needed to determine causality,
      potential bidirectional associations, and underlying mechanisms such as using
      media to (mis)manage negative emotions. Media use is important to assess and
      monitor and may be a significant intervention target when addressing sleep and
      internalizing problems, and possible underlying cognitive-emotional processes in
      adolescents with ADHD.

PMID- 30223188
TI  - Deepwater Horizon oil alone and in conjunction with Vibrio anguillarum exposure
      modulates immune response and growth in red snapper (Lutjanus campechanus).
AB  - This study examined the impacts of Macondo oil from the Deepwater Horizon oil
      spill, both alone and in conjunction with exposure to the known fish pathogen
      Vibrio anguillarum, on the expression of five immune-related gene transcripts of
      red snapper (il8, il10, tnfa, il1b, and igm). In order to elucidate this impact,
      six different test conditions were used: one Control group (No oil/No pathogen),
      one Low oil/No pathogen group (tPAH50 = 0.563 MUg/L), one High oil/No pathogen
      group (tPAH50 = 17.084 MUg/L, one No oil/Pathogen group, one Low oil/Pathogen
      group (tPAH50 = 0.736 MUg/L), and one High oil/Pathogen group (tPAH50 = 15.799
      MUg/L). Fish were exposed to their respective oil concentrations for one week. On
      day 7 of the experiment, all fish were placed into new tanks (with or without V.
      anguillarum) for one hour. At three time points (day 8, day 10, and day 17), fish
      organs were harvested and placed into RNAlater, and qPCR was run for examination
      of the above specific immune genes as well as cyp1a1. Our results suggest that
      cyp1a1 transcripts were upregulated in oil-exposed groups throughout the
      experiment, confirming oil exposure, and that all five immune gene transcripts
      were upregulated on day 8, but were generally downregulated or showed no
      differences from controls on days 10 and 17. Finally, both oil and pathogen
      exposure had impacts on growth.

PMID- 30223189
TI  - Plant mRNA decay: extended roles and potential determinants.
AB  - The decay of mRNA in plants is tightly controlled and shapes the transcriptome.
      The roles of this process are to digest RNA as well as to suppress exogenous and
      endogenous gene silencing by preventing siRNA generation. Recent evidence
      suggests that mRNA decay also regulates the accumulation of the putative 3'
      fragment-derived long non-coding RNAs (3'lncRNAs). The generation of siRNA or
      3'lncRNA from a selective subset of mRNAs raises a fundamental question of how
      the mRNA decay machineries select and determine their substrate transcripts for
      distinctive decay destiny. Evidence for potential mRNA decay determinants, such
      as codon bias, GC content and N6-methyladenosine (m6A) modification, is rapidly
      emerging. This paper aims to review the recent discoveries in plant mRNA decay.

PMID- 30223190
TI  - Initiation and engagement as mechanisms for change caused by collaborative care
      in opioid and alcohol use disorders.
AB  - BACKGROUND: To assess the mechanism by which a collaborative care (CC)
      intervention improves self-reported abstinence among primary care patients with
      opioid and alcohol use disorders (OAUD) compared to treatment as usual. METHODS:
      Secondary data analysis of SUMMIT, a randomized controlled trial of CC for OAUD.
      Participants were 258 patients with OAUD receiving primary care at a multi-site
      Federally Qualified Health Center. Using a mediation analysis decomposition of a
      total effect into a mediated and a direct effect, we examined the effect of CC on
      abstinence at six months, attributable to the HEDIS treatment initiation and
      engagement measures for the total sample, for individuals with alcohol use
      disorders alone, and for those with a co-morbid opioid use disorder. RESULTS:
      Although the CC intervention led to an increase in both initiation and
      engagement, among the full sample, only initiation mediated the effect of the
      intervention on abstinence (3.8%, CI=[0.4%, 8.3%]; 32% proportion of the total
      effect). In subgroup analyses, among individuals with comorbid alcohol and opioid
      use disorders, almost 100% of the total effect was mediated by engagement, but
      the effect was not significant. This was not observed among the alcohol use
      disorder only group. CONCLUSIONS: Among primary care patients with OAUDs,
      treatment initiation partially mediated the effect of CC on abstinence at 6
      months. The current study emphasizes the importance of primary care patients
      returning for a second substance-use related visit after identification. CC may
      work differently for people with co-morbid opioid use disorders vs. alcohol use
      disorders alone.

PMID- 30223191
TI  - Nicorandil ameliorates pulmonary inflammation and fibrosis in a rat model of
      silicosis.
AB  - Nicorandil, an antianginal and potassium channel opener agent, has different
      useful impacts on cardiovascular and respiratory systems. Its effect against
      silicosis has not been discussed yet, therefore, this is an attempt to decide
      whether nicorandil can reduce silica-induced lung injury in rats. Silica model
      was induced by intranasal instillation of silica dust once. Rats were given
      nicorandil for 56 days after exposure to silica. Results showed that nicorandil
      significantly alleviated silica-induced inflammation as it decreased the elevated
      levels of total and differential cell counts, pulmonary edema (revealed by
      decreased lung/body weight ratio and W/D weight ratio), LDH and total protein
      levels in BALF. Notably, nicorandil decreased collagen deposition as evidenced by
      reduction in levels of hydroxyproline and collagen in lung tissues as well as
      obvious alleviation in silica-induced fibrosis in histopathological findings.
      Nicorandil effectively reduced the increased expression of NF-kappaB and iNOS and
      decreased MPO levels in lung tissues. Moreover, nicorandil abolished oxidative
      and nitrosative stress via reducing levels of pulmonary MDA and NOx concomitant
      with elevating levels of pulmonary GSH and SOD. Meanwhile, nicorandil decreased
      the levels of TNF-alpha and TGF-beta, up regulated Nrf-2 and HO-1 levels in BALF
      suggesting antioxidant, anti-inflammatory and antifibrotic properties. In
      summary, nicorandil can confer protection against silica-induced lung
      inflammation and fibrosis. This impact might be due to its ability to down
      regulate the production of inflammatory and fibrotic cytokines in addition to
      restoring oxidant/antioxidant balance.

PMID- 30223192
TI  - Low serum concentration of free triiodothyronine (FT3) is associated with
      increased risk of Alzheimer's disease.
AB  - BACKGROUND: In epidemiological studies, thyroid hormones (THs) have been
      associated with the risk of dementia. However, little is known of the relation
      between THs and risk of Alzheimer's disease (AD) or vascular dementia (VaD) in a
      memory clinic population. METHODS: In a mono-center study, serum concentrations
      of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free
      triiodothyronine (FT3) were assessed in 302 patients. All patients had subjective
      or objective mild cognitive impairment and none received treatment with THs. Cox
      proportional hazards regression analyses was used to determine whether THs at
      baseline were associated with the risk of conversion to all-cause dementia, AD or
      VaD. RESULTS: During the follow-up (mean 2.8 years), 82 (28%) of the patients
      progressed to dementia [AD, n = 55 (18%) and VaD, n = 17 (6%)]. Serum
      concentrations of TSH, FT4, and FT3 did not associate with all-cause dementia or
      VaD. Higher serum FT3 was associated with lower risk of conversion to AD [hazard
      ratio (HR) = 054; 95% confidence interval (CI): 0.32-0.92 per 1 pmol/L increase].
      Furthermore, patients in the lowest serum FT3 quartile had a twofold increased
      risk of AD compared to those in the highest quartile (HR = 2.63; 95% CI: 1.06
      6.47). These associations remained after adjustment for multiple covariates.
      CONCLUSIONS: In a memory clinic population, there was an inverse, linear
      association between serum FT3 and risk of AD whereas THs did not associate with
      all-cause dementia or VaD. Further studies are needed to determine the underlying
      mechanisms as well as the clinical significance of these findings.

PMID- 30223193
TI  - Prenatal maternal psychopathology and stress and offspring HPA axis function at 6
      years.
AB  - OBJECTIVE: Intrauterine exposures such as maternal psychopathology and stress are
      known to influence the physical and mental health of the offspring. One of the
      proposed pathways underlying these associations is dysregulated hypothalamic
      pituitary-adrenal (HPA) axis activity in the offspring. This study examined the
      relation of perinatal maternal symptoms of psychopathology and stress with
      offspring HPA axis activity at 6 years as measured by hair cortisol and cortisone
      concentrations. METHODS: The study was part of the population-based Generation R
      Study, a prospective population-based cohort from fetal life onwards. 2546
      children and their mothers formed the study population. Perinatal maternal
      psychopathology and stress were assessed by questionnaires in the second and
      third trimester. Principal components for both psychopathology and stress were
      created to reduce the number of explanatory variables. Child hair samples for
      cortisol and cortisone measurements were collected at the age of 6. Linear
      regression analysis, adjusted for covariates, was used to examine associations
      between maternal psychopathology and stress and child hair cortisol and cortisone
      levels. RESULTS: The maternal psychopathology principal component was associated
      with higher child hair cortisone (adjusted B = 0.24, 95%CI 0.08;0.40, p-value <
      0.01). Effect estimates of the individual dimensions ranged from 0.97 (95%CI
      0.21;1.73, p-value = 0.01) for interpersonal sensitivity to 1.67 (95%CI
      0.86;2.47, p-value < 0.01) for paranoid ideation. In addition, children exposed
      to intrauterine stress, as measured by the principal component, had higher hair
      cortisone levels (adjusted B = 0.54, 95%CI 0.21;0.88, p-value < 0.01). Exposure
      to maternal psychopathology and stress was not associated with offspring hair
      cortisol. Stratification by child sex resulted in associations between maternal
      symptoms of psychopathology during pregnancy and child hair cortisone levels in
      boys and associations between maternal symptoms of stress during pregnancy and
      child hair cortisone levels in girls. CONCLUSION: Our results suggest that
      maternal psychopathology and stress during pregnancy are associated with long
      term HPA axis activity of the offspring. The association of maternal
      psychopathology and stress during pregnancy with offspring hair cortisone levels
      is a novel finding. Future studies should examine whether these
      psychophysiological differences between exposed and non-exposed children underlie
      offspring morbidity associated with maternal psychopathology and stress during
      pregnancy.

PMID- 30223194
TI  - Cell-to-cell contact mechanism modulates Starmerella bacillaris death in mixed
      culture fermentations with Saccharomyces cerevisiae.
AB  - The use of mixed culture fermentations with selected Starmerella bacillaris and
      Saccharomyces cerevisiae strains is gaining winemaking attention, mainly due to
      their ability to enhance particular characteristics in the resulting wines. In
      this context, yeast interspecies interactions during fermentation have a
      fundamental role to determine the desired product characteristics, since they may
      modulate yeast growth and as a consequence metabolite production. In order to get
      an insight into these interactions, the growth and death kinetics of the
      abovementioned species were investigated in pure and mixed culture fermentations,
      using cv. Nebbiolo grape must. Trials were conducted in flasks but also in a
      double-compartment fermentation system in which cells of the two species were
      kept separate by a filter membrane. Although the two species had similar growth
      pattern during the first days of fermentation, Starm. bacillaris died earlier
      when tested in the flask than in the double-compartment fermentor. The early
      death of Starm. bacillaris seemed to be not caused by nutrient limitation nor by
      accumulation of growth inhibitory compounds (which were not measured in the
      present study). Rather, cell-to-cell contact mechanism, dependent on the presence
      of viable S. cerevisiae cells, appears to be responsible for the observations
      made. These results contribute to better understand the factors that influence
      Starm. bacillaris death during wine fermentations.

PMID- 30223195
TI  - Quantitative proteomics reveals the crucial role of YbgC for Salmonella enterica
      serovar Enteritidis survival in egg white.
AB  - Salmonella enterica serovar Enteritidis (S. Enteritidis) is a food-borne
      bacterial pathogen that can cause human salmonellosis predominately by
      contamination of eggs and egg products. However, its survival mechanisms in egg
      white are not fully understood, especially from a proteomic point of view. In
      this study, the proteomic profiles of S. Enteritidis in Luria-Bertani (LB) broth
      containing 50% and 80% egg white, and in whole egg white were compared with the
      profile in LB broth using iTRAQ technology to identify key proteins that were
      involved in S. Enteritidis survival in egg white. It was found that there were
      303, 284 and 273 differentially expressed proteins in S. Enteritidis after 6 h
      exposure to whole, 80% and 50% egg white, respectively. Most of up-regulated
      proteins were primarily associated with iron acquisition, cofactor and amino acid
      biosynthesis, transporter, regulation and stress responses, whereas down
      regulated proteins were mainly involved in energy metabolism, virulence as well
      as motility and chemotaxis. Three stress response-related proteins (YbgC, TolQ,
      TolA) of the tol-pal system responsible for maintaining cell membrane stability
      of Gram-negative bacteria were up-regulated in S. Enteritidis in response to
      whole egg white. Interestingly, deletion of ybgC resulted in a decreased
      resistance of S. Enteritidis to egg white. Compared with the wild type and
      complementary strains, a 3-log population reduction was observed in ?ybgC mutant
      strain after incubation in whole egg white for 24 h. Cellular morphology of ?ybgC
      mutant strain was altered from rods to spheres along with cell lysis in whole egg
      white. Furthermore, deletion of ybgC decreased the expression of tol-pal system
      related genes (tolR, tolA). Collectively, these proteomic and mutagenic analysis
      reveal that YbgC is essential for S. Enteritidis survival in egg white.

PMID- 30223196
TI  - The complex genetic and psychosocial influences on polysubstance misuse.
AB  - Polysubstance misuse is a costly and complex behavioral phenotype that is
      concurrent with internalizing and externalizing disorders. Research on genetic
      and psychosocial influences suggests that a life course framework composed of a
      transactional etiology sheds light on the complex nature of polysubstance misuse.
      Further, given the extensive comorbidity with mental illness and behavioral
      dysregulation, viewing polysubstance misuse as asymmetrical in the population is
      helpful for guiding broad decision-making around prevention and policy.

PMID- 30223197
TI  - Mango seed causing acute large bowel obstruction in descending colon-world's
      first reported case.
AB  - INTRODUCTION: Phytobezoars are a very rare cause of large bowel obstruction.
      Mango seeds as a phytobezoar causing large bowel obstruction have not been
      reported in the English literature. PRESENTATION OF CASE: We present the case of
      a 69 years old female who presented to us with clinical and radiological signs of
      acute large bowel obstruction. On laparotomy, it was noted that mango seeds as a
      phytobezoar was responsible for the obstruction in the descending colon.
      DISCUSSION: Phytobezoars are a rare but known cause of small bowel obstruction.
      Large bowel obstruction is even rarer. The literature has documented a few cases
      of small bowel obstruction caused by mango seeds but none for large bowel
      obstruction. The most frequent reported sites of large bowel obstruction are the
      sigmoid colon and recto-sigmoid junction. However, phytobezoar causing descending
      colonic obstruction without any pre-existing underlying pathology has not been
      reported. CONCLUSION: The association of bezoar with acute large bowel
      obstruction is a very rare however; it must be entertained in the differential
      diagnosis of any large bowel obstruction. Early diagnosis and treatment can avoid
      lethal complications. Our case being the first case of mango seeds phytobezoar in
      descending colon with acute large bowel obstruction; signifies its importance for
      reporting in the English literature.

PMID- 30223198
TI  - The relationship between morningness-eveningness and resilience in mood disorder
      patients.
AB  - BACKGROUND: There is some evidence that resilience is related to mental illness.
      Patients with a mood disorder have a tendency to show eveningness, and they tend
      to be less resilient. However, no study has investigated the association between
      resilience and morningness-eveningness in patients with a mood disorder. The aim
      of this study was to explore whether morningness-eveningness is related to
      resilience in patients with a mood disorder. METHODS: We recruited 224 patients
      with major depressive disorder (MDD), 77 with bipolar disorder (BD), and 958
      control participants. Morningness-eveningness and resilience were evaluated using
      the Composite Scale of Morningness (CS) and the Connor-Davidson Resilience Scale
      (CD-RISC), respectively. RESULTS: The CD-RISC scores were significantly lower in
      patients with MDD, followed by those with BD, than those of the control group.
      The CD-RISC score was positively correlated with the CS score in patients with
      MDD and BD. Multiple linear regression analyses revealed that the CS score was
      significantly associated with the CD-RISC score after controlling for the
      possible influence of age, gender, length of education, economic status, onset
      age, and suicide attempt history in the MDD group. However, the association did
      not reach statistical significance in patients with BD. CONCLUSIONS: Higher
      resilience was positively correlated with morningness in patients with MDD or BD.
      In multiple regression analysis, a significant linear relationship was observed
      between resilience and morningness only in patients with MDD. The biological
      mechanism underlying the relationship between morningness-eveningness and
      resilience should be explored.

PMID- 30223199
TI  - Macroporous monoliths with pH-induced switchable wettability for recyclable oil
      separation and recovery.
AB  - HYPOTHESIS: The effective separation and recovery of oils from water is important
      for the protections of ecosystems and the environment. Polymeric porous monoliths
      have been demonstrated as attractive absorbents for oil/water separation.
      However, the recyclability was mainly realized by squeezing, combustion, or
      centrifugation, which may restrict in elastic materials, destroy the adsorbates
      or need special apparatus. Thus it is desirable to developing monoliths with
      controllable oil absorption and desorption. EXPERIMENTS: A series of "smart"
      monoliths with pH-induced switchable wettability were fabricated by high internal
      phase emulsion (HIPE) polymerization and epoxide ring-opening for the
      incorporation of amine groups. The resultant monoliths and their wettabilities
      were examined using Fourier transform infrared spectroscopy (FTIR), scanning
      electron microscopy (SEM), nitrogen adsorption/desorption and contact angle
      analysis, respectively. The oil separation efficiency and recyclability were
      evaluated. FINDINGS: The monoliths with macroporous structure can undergo
      switchable wettability under reversible pH stimulation. As an absorbent, the
      monoliths not only separated and recovered organic solvents and oils (including
      crude oil) from aqueous mixtures through a reversible and recyclable absorption
      and desorption process upon alternating the pH between 7.0 and 1.0, but also
      continuously expulsed oils from water surfaces in a continuous manner with the
      aid of external driving pressures. Moreover, the monoliths also allowed the
      effective separation of surfactant-free and surfactant-stabilized oil-in-water
      emulsions with high separation efficiency.

PMID- 30223200
TI  - Flexibility of inactive electrokinetic layer at charged solid-liquid interface in
      response to bulk ion concentration.
AB  - It has been a long-lasting debate on the position of zeta potential plane within
      aqueous solutions. This paper reports a flexible behavior of the inactive
      electrokinetic layer between the outer-Helmholtz plane and zeta potential plane,
      so-called buffer layer, in response to bulk ion concentration. This flexibility
      is not only corroborated by analyzing the measured zeta potentials with resulting
      electrical quad-layer model (inner- and outer-Helmholtz, buffer, and diffuse
      layers) but also consistent with thermodynamic analysis. The model indicates that
      the flexible buffer layer thickness saturates to its minimum for concentrated
      solutions. The predicted ionic conductance agrees well with the previous
      experimental measurements in nanochannels. The theory provides a deep physical
      insight into understanding, design, and manipulation of ion transport in
      nanosystems.

PMID- 30223201
TI  - The impact of power generation emissions on ambient PM2.5 pollution and human
      health in China and India.
AB  - Emissions from power plants in China and India contain a myriad of fine
      particulate matter (PM2.5, PM <= 2.5 MUm in diameter) precursors, posing
      significant health risks among large, densely settled populations. Studies
      isolating the contributions of various source classes and geographic regions are
      limited in China and India, but such information could be helpful for policy
      makers attempting to identify efficient mitigation strategies. We quantified the
      impact of power generation emissions on annual mean PM2.5 concentrations using
      the state-of-the-art atmospheric chemistry model WRF-Chem (Weather Research
      Forecasting model coupled with Chemistry) in China and India. Evaluations using
      nationwide surface measurements show the model performs reasonably well. We
      calculated province-specific annual changes in mortality and life expectancy due
      to power generation emissions generated PM2.5 using the Integrated Exposure
      Response (IER) model, recently updated IER parameters from Global Burden of
      Disease (GBD) 2015, population data, and the World Health Organization (WHO) life
      tables for China and India. We estimate that 15 million (95% Confidence Interval
      (CI): 10 to 21 million) years of life lost can be avoided in China each year and
      11 million (95% CI: 7 to 15 million) in India by eliminating power generation
      emissions. Priorities in upgrading existing power generating technologies should
      be given to Shandong, Henan, and Sichuan provinces in China, and Uttar Pradesh
      state in India due to their dominant contributions to the current health risks.

PMID- 30223202
TI  - Enhanced health risks from exposure to environmentally persistent free radicals
      and the oxidative stress of PM2.5 from Asian dust storms in Erenhot, Zhangbei and
      Jinan, China.
AB  - Asian dust storms can increase the level of atmospheric pollution over regions
      downwind of dust storms and may have adverse health effects on residents along
      the sandstorm transmission route. This study was the first to report the
      concentration levels, properties and possible sources of environmentally
      persistent free radicals (EPFRs) and oxidative potential in atmospheric PM2.5 at
      the three sites of Erenhot, Zhangbei, and Jinan along the transport route of
      Asian dust storms during the occurrence of Asian dust storms in the spring of
      2016. Under non-sandstorm weather conditions, the average EPFR concentrations at
      the three sites were Zhangbei>Jinan>Erenhot, while the PM-induced oxidative
      potential levels were Erenhot>Jinan>Zhangbei. The PM2.5 concentration increased
      significantly during dust storm events, and the total atmospheric concentration
      of EPFRs (spins/m3) and total oxidation potential (a.u./m3) of PM2.5
      simultaneously increased. However, the EPFR concentration in PM2.5 (spins/g) and
      the unit mass of the PM oxidation potential (a.u./g) were significantly reduced.
      Electron paramagnetic resonance analysis combined with backward trajectory
      analysis and MODIS products showed that Asian dust storms can carry EPFRs over
      long distances. Correlation analysis showed that the atmospheric concentrations
      of EPFRs were positively correlated with elemental carbon (EC) for the Zhangbei
      and Jinan samples but were not significantly correlated with EC for the Erenhot
      samples, indicating that combustion may be an important source of EPFRs for the
      Zhangbei and Jinan samples. In contrast, the EPFRs in the Erenhot samples were
      more affected by dust/sand. The EPFR concentration levels showed a significant
      positive correlation with the oxidation potentials for the Erenhot and Zhangbei
      samples and showed negative correlations for the Jinan samples, suggesting that
      the EPFRs in the Erenhot and Zhangbei samples may provide an important
      contribution to the oxidative stress in PM2.5. In contrast, the oxidation
      potential for the Jinan samples was mainly caused by substances other than EPFRs.
      This study presents a basic understanding of the potential health effects of
      Asian dust storms, and this information can be used to assess the health risks of
      Asian dust storms in future studies.

PMID- 30223203
TI  - Maternal exposure to bisphenol A and anogenital distance throughout infancy: A
      longitudinal study from Shanghai, China.
AB  - BACKGROUND: Bisphenol A (BPA) is one of the most common endocrine-disrupting
      compounds (EDCs) with a ubiquitous presence. Both animal and human studies have
      reported the association between maternal exposure to BPA and anogenital distance
      (AGD) in offspring. However, the results are conflicting and the longitudinal
      effect is unknown. We aimed to examine the effect of maternal exposure to BPA on
      AGD in offspring in a longitudinal birth cohort from birth to 1 year of age.
      METHODS: BPA was assayed using urine samples collected at 12-16 gestational weeks
      from 982 pregnant participants who later delivered infants. Infants' AGDs (AGDap
      [anus-penis] and AGDas [anus-scrotum] for boys, AGDac [anus-clitoris] and AGDaf
      [anus-fourchette] for girls) were measured at birth, and at 6 and 12 months of
      age. Multiple linear regression analysis was conducted to examine the
      associations between maternal exposure to BPA and offspring's AGDs. Then
      generalized estimating equation (GEE) model was applied to make use of the
      repeated measurements of AGDs and examine the overall effect of maternal exposure
      to BPA. RESULTS: Compared to boys with undetected maternal BPA, those with
      detected BPA were more likely to have shorter AGDap and AGDas at 6 and 12 months.
      However, the differences were statistically significant for AGDap and AGDas only
      at 12 months (2.87 and 4.12 mm shorter, respectively). In GEE models, similar
      patterns were observed. Boys in the higher quartiles were more likely to have
      shorter AGDap and AGDas than those in the first quartile. However, statistically
      significant differences were only observed in boys in the third quartile. For
      girls, these associations were not observed regardless of the timing of
      measurements (at birth, 6 months and 12 months). CONCLUSIONS: Maternal exposure
      to BPA was associated with shortened AGDap and AGDas in boys at age 12 months but
      not in girls, which suggests a gender specific effect of BPA exposure on
      offspring's development.

PMID- 30223204
TI  - Urinary phthalate metabolites in relation to childhood asthmatic and allergic
      symptoms in Shanghai.
AB  - BACKGROUND: Few studies can be found on phthalate exposure in relation to
      childhood asthma and allergic symptoms from Mainland China, where a persistent
      increase in prevalence of childhood asthma and allergic disease has been
      observed. OBJECTIVES: This study aimed to assess the exposure levels to
      phthalates and its relationship with asthmatic and allergic symptoms among
      children in Shanghai, which has the highest prevalence of childhood asthma in
      Mainland China. METHODS: A follow-up study (2013-2014) of 434 children aged 5-10
      years was conducted, based on the China, Children, Homes, Health (CCHH) study
      (2011-2012) in Shanghai, China. Information on asthmatic and allergic symptoms
      (wheeze, rhinitis, and eczema) were collected using validated questionnaires. Ten
      phthalate metabolites in morning urine samples were analyzed by high-performance
      liquid chromatography with triple quadrupole tandem mass spectrometry (HPLC
      MS/MS). Multivariable logistic regression was used to estimate the associations
      between symptoms and urinary phthalate metabolites controlling for demographics,
      family history of allergic diseases and other covariates. RESULTS: Nine out of 10
      phthalate metabolites were detected in all subjects (average detection rate of
      93.2%). By multivariable logistic regression analyses, the 4th quartile of Mono-n
      butyl phthalate (MnBP) (reference: 1st quartile) had adjusted prevalence odds
      ratios (aPORS) and 95% confidence intervals (95%CIs) of 2.27(1.06-4.88),
      2.14(1.02-4.46) and 2.98(1.19-7.50) for wheeze, rhinitis and eczema,
      respectively, while those of Mono-isobutyl phthalate (MiBP) were 2.23(1.08-4.62)
      and 2.96(1.02-8.60) for rhinitis and eczema, respectively. The highest quartile
      of mono-2-ethyl-5-hydroxyhexyl phthalate(MEHHP) and mono-2-ethyl-5-oxohexyl
      phthalate(MEOHP) had aPORS and 95%CIs of 3.10(1.10-8.74) and 2.63(1.02-6.80) for
      eczema, respectively. By summing up the 4 low molecular weight metabolites
      (?4LMWP) and all 9 metabolites (?9Total), the highest quartiles of ?4LMWP
      and?9Total were significantly associated with all symptoms. In most of the above
      associations, a significantly increasing trend from the 1st to the 4th quartile
      was observed. Subjects with 2 or 3 concomitant symptoms (reference: no symptoms)
      had significant positive associations with a higher level (the 4th quartile) of
      phthalate metabolites. CONCLUSIONS: Low MW metabolites such as MnBP and MiBP,
      high MW DEHP and the total amount of phthalate metabolites might have adverse
      health effects on asthma and allergic symptoms in Chinese children.

PMID- 30223206
TI  - Examining the effect of cue exposure and introspective responses to cues on
      impulsivity in restrained and unrestrained eaters.
AB  - The current study extends cue-reactivity research by evaluating impulsive
      valuation as an outcome of exposure to food cues. This study also separates
      introspection after viewing cues (e.g., responding to questions about craving and
      affect) from mere cue exposure, to examine if introspection changes self
      regulation behaviors in response to food cues. Finally, we compared restrained
      and unrestrained eaters to ascertain the influence of motivation toward food on
      how cue-reactivity influences impulsive behavior. In the current study,
      restrained and unrestrained eaters were randomly assigned to view food or neutral
      cues and were randomized to respond to cues with either craving and affect
      questions (e.g., introspection) or filler questions. Following cue exposure,
      participants completed a purchase task as a measure of impulsive lack of self
      control. Results revealed that unrestrained eaters who introspected on craving
      and affect showed decreased impulsive behavior, whereas restrained eaters who
      introspected on craving and affect showed increased impulsive behavior. Although
      there was no effect of food cues on impulsive behavior, the interaction of
      introspective response and restraint status suggests that attending to craving
      and affect has differential effects on subsequent self-control behavior for
      restrained and unrestrained eaters. Implications for further cue-reactivity work
      and treatment of chronic dieters (i.e., restrained eaters) will be discussed.

PMID- 30223207
TI  - Direct versus indirect measurement of digit ratio: New data from Austria and a
      critical consideration of clarity of report in 2D:4D studies.
AB  - BACKGROUND: Digit ratio (2D:4D), has been the subject of many studies. However,
      the best method of measuring digit length, either directly (d2D:4D) or indirectly
      (i2D:4D), is controversial. In many reports i2D:4D has been found to show a
      directional effect such that d2D:4D > i2D:4D. The exception is three studies from
      one group of researchers in Austria. Thus, it is unclear whether this effect is
      nation- or lab-specific. AIMS: To examine evidence for effects of direct versus
      indirect measurements of mean 2D:4D in Austrians. STUDY DESIGN: We compared 2D:4D
      based on direct and indirect measurements of digit lengths of Austrians.
      SUBJECTS: There were 80 participants, 21 adults and 59 children. OUTCOME
      MEASURES: 2D:4D of right and left hands, measured directly (from the palm) and
      indirectly (from hand scans). RESULTS: Repeatability was high for both d2D:4D and
      i2D:4D, with the latter slightly higher than the former. d2D:4D and i2D:4D
      correlated strongly and the sex difference in 2D:4D (males < females) was greater
      for i2D:4D. With regard to directional differences, we found d2D:4D > i2D:4D for
      both right (d = -0.53) and left hands (d = -0.80). CONCLUSION: There was no
      evidence of an "Austrian" effect on direct versus indirect measurements of 2D:4D,
      i.e. mean d2D:4D was greater than i2D:4D. We discuss our findings in the light of
      issues regarding "clarity of report" from earlier Austrian studies.

PMID- 30223205
TI  - Associations between school lunch consumption and urinary phthalate metabolite
      concentrations in US children and adolescents: Results from NHANES 2003-2014.
AB  - Diet is a major route of phthalate exposure in humans due to use in food
      packaging materials. School lunches may be an important contributor to phthalate
      exposure in children and adolescents in the US because of the large amount of
      packaging necessary for mass-produced foods. We used 2003-2014 National Health
      and Nutrition Examination Survey data to study the association between school
      lunch consumption and urinary phthalate metabolite concentrations in children
      (ages 6-11 years, N = 2196) and adolescents (ages 12-19 years, N = 2314). After
      adjustment for other covariates, children who Always consumed school lunch had
      significantly elevated urinary concentrations of the following phthalate
      metabolites compared to levels in children who Never ate school lunch: sum of
      di(2-ethylhexyl) phthalate metabolites, (28% higher, 95% confidence interval, CI:
      10, 49%); mono-(carboxy-octyl) phthalate (MCOP; 43% higher, 95% CI: 17, 76%) and
      mono-n-butyl phthalate (18% higher, 95% CI: 3.5, 34%). We did not find
      statistically significant associations in adolescents, but the trend for MCOP
      concentrations was similar to that of children. In sensitivity analyses,
      associations between 24-hour recall of cafeteria food and urinary phthalate
      metabolites were not statistically significant, which could indicate that
      associations observed with Always consuming school lunch are due to residual
      confounding. Our findings show that children who Always eat school lunch had
      higher levels of exposure to some phthalates, but the source of differences in
      exposure need to be evaluated in additional studies.

PMID- 30223208
TI  - Assessment and estimation of 65Zn production yield via neutron induced reaction
      on natZnO and natZnONPs.
AB  - Zinc-65 has been of great interest in medical, biomedical, agricultural, and
      industrial applications due to its suitable half-life and decay properties. The
      65Zn was produced via neutron irradiation on natural zinc oxide and natural zinc
      oxide nanoparticles targets in Tehran Research Reactor (TRR) at a thermal neutron
      flux of 4.5 * 1013 n cm-2 s-1 for 30 min. The excitation function of
      64Zn(n,gamma)65Zn reaction was calculated via the TALYS-1.8 code. The MCNPX code
      was used to calculate the thermal neutron distribution. The 65Zn theoretical
      production yield was estimated using calculated cross sections and the calculated
      thermal neutron distribution. The obtained experimental data and simulated value
      of production yield for 65Zn were in reasonable agreement.

PMID- 30223209
TI  - Transitioning from the level surface to stairs in children with and without Down
      syndrome: Motor strategy and anticipatory locomotor adjustments.
AB  - BACKGROUND: Children with Down syndrome (DS) show underdeveloped motor strategy
      and anticipatory locomotor adjustments (ALA) before crossing an obstacle. Stairs
      presents another important setting to study environment navigation and motor
      adaptation. Inclusion of external ankle load is often used to perturb the
      stability of a system and observe the emergence of new patterns. RESEARCH
      QUESTION: How do stair height and external ankle load affect motor strategy and
      ALA in 5-to-11-year-old children with typical development (TD) and with DS when
      approaching the stairs? METHODS: Fourteen children with DS and 14 age- and sex
      matched children with TD participated in the study. They walked along a 5-meter
      walkway and ascended 3-step staircases. There were three staircases (low,
      moderate, and high heights) and 2 loading conditions (no load and ankle load). A
      3D motion capture system was used to collect data. Motor strategy was coded for
      each trial. Step length, width, time, and velocity, minimum toe clearance, and
      horizontal toe velocity were calculated for the last four steps before stair
      ascent. Mixed ANOVAs with repeated measures were conducted for statistical
      analysis. RESULTS: The TD group walked up all the stairs, while the DS group
      displayed a strategy shift from walking to crawling when the stairs became
      higher. While the TD group maintained the values of most spatiotemporal
      variables, the DS group continuously decreased step length and velocity but not
      step width over the last four approaching steps. Ankle load decreased step
      length, step velocity, minimum toe clearance, and horizontal toe velocity in the
      DS group, to a greater extent, than in the TD group. SIGNIFICANCE: Children with
      DS show underdeveloped motor strategy and ALA when approaching the stairs, and
      external ankle load further disrupts these patterns. Stair negotiation appears to
      be an effective assessment tool for evaluating motor adaptation in children with
      DS.

PMID- 30223210
TI  - Reliability of scapular kinematics estimated with three-dimensional motion
      analysis during shoulder elevation and flexion.
AB  - BACKGROUND: Knowing the reliability of three-dimensional motion analysis to
      evaluate scapular kinematics during upper limb movements is essential to plan
      further research dedicated to understanding scapulothoracic joint movements
      relative to the global shoulder motion. RESEARCH QUESTION: The aim of this study
      was to assess the intra-subject as well as intra- and interrater reliability of
      scapulothoracic joint angles during shoulder elevation in scapular plane and
      shoulder flexion. METHODS: Twenty healthy participants (26.6 +/- 3.5 years) were
      asked to perform maximum shoulder elevation in scapular plane as well as shoulder
      flexion. Reliability was assessed using the intraclass correlation coefficient
      (ICC) and its 95% confidence interval of scapular kinematics (rotation, tilting,
      pro-retraction) at each degree of global motion (shoulder elevation or shoulder
      flexion) between 0 degrees  to 150 degrees . RESULTS: ICCs above 0.60 were
      accepted as good indicators for reliability. Intra-subject reliability was found
      to be very high (>0.9 for most part) for all scapulothoracic joint angles during
      both movements. Intra- and interrater reliability also showed good reliability
      being above 0.60 for the most part (except scapula tilting during shoulder
      elevation). Scapular kinematics showed low reliability during the respective
      first 10 degrees  and 20 degrees  of shoulder elevation and shoulder flexion.
      Furthermore, decreasing reliability was found above 120 degrees  of shoulder
      elevation or flexion. SIGNIFICANCE: This study generally showed good to high
      levels of reliability in the range of interest (20-120 degrees ) in evaluating
      scapula kinematics in healthy adults during shoulder elevation and flexion; these
      results are important for future research providing a better understanding of
      scapular kinematics.

PMID- 30223211
TI  - Effect of pore geometry on the fatigue properties and cell affinity of porous
      titanium scaffolds fabricated by selective laser melting.
AB  - Porous titanium scaffolds with different unit cell type (tetrahedron and
      octahedron) and pore size (500 um and 1000 um) were fabricated by selective laser
      melting (SLM), and the effects of unit cell type and pore size on their fatigue
      properties and cell affinity were studied. The fatigue properties were performed
      by static and dynamic mechanical testing, while the cell affinity was evaluated
      in vitro with mouse osteoblast cells. It was found that octahedron scaffolds
      exhibited superior static mechanical properties, longer fatigue lives and higher
      fatigue strength in comparison to those of tetrahedron ones. As expected,
      scaffolds with 1000 um pore resulted in lower compressive properties and shorter
      fatigue lives compared to those with 500 um pore. The differences were analyzed
      based on the unit cell structure, porosity, and manufacturing imperfections.
      Scanning electron microscopy (SEM) and immunofluorescence showed that cells
      spread better on octahedron scaffolds than those on tetrahedron ones. Meanwhile,
      the scaffolds with 1000 um pore were more suitable for cell attachment and growth
      within the same unit cell owing to higher porosity. The comparison of different
      pore geometry on the mechanical and biological property provided further insight
      into designing an optimal porous scaffold.

PMID- 30223212
TI  - The effect of 3D-printed Ti6Al4V scaffolds with various macropore structures on
      osteointegration and osteogenesis: A biomechanical evaluation.
AB  - A properly designed porous scaffold can accelerate the osseointegration process,
      and the use of computer-aided design (CAD) and additive manufacturing (AM)
      techniques has the potential to improve the traditional porous scaffold approach.
      In this study, we evaluate the effect of porous Ti6Al4V (Ti) with different pore
      structures on osteointegration and osteogenesis. Porous Ti scaffolds with
      different pore structures based on four commercially available implants were
      designed and manufactured by CAD and selective laser melting (SLM). Micro-CT
      showed that SLM was able to produce Ti scaffolds with different pore structures.
      The mechanical properties evaluated by finite element analysis and compression
      tests indicated that the four porous scaffolds in our study were mechanically
      adapted, despite their different mechanical properties. Then, we used 3D-printed
      porous discs to culture human bone marrow mesenchymal stem cells (hBMMSCs), the
      main seed cells of bone tissue engineering. The results showed no significant
      difference among the four groups in cell morphology, viability and proliferation.
      In addition, four groups showed a comparable mineralization ability even though
      Ti-g had a higher alkaline phosphatase activity (ALP). In vivo tests in a rabbit
      model showed that all four groups were suitable for new bone ingrowth and
      integration. These findings indicate that the four different pore structures in
      the Ti scaffolds provided good osteointegration and osteogenesis.

PMID- 30223213
TI  - Precision of different fatigue methods for predicting glass-ceramic failure.
AB  - This study aimed to characterize the fatigue behavior using two fatigue methods,
      boundary and staircase, and to predict the probability of failure (Pf) of
      zirconia-reinforced lithium silicate glass-ceramic (ZLS). Bar-shaped specimens of
      ZLS (18 *4 *1.2 mm) were fabricated. Thirty specimens were subjected to a three
      point flexural strength test using a universal testing machine with 0.5 mm/min
      crosshead speed, in 37  degrees C distilled water. Flexural strength data were
      analyzed with Weibull statistics. Eighty-six bars were subjected to cyclic
      fatigue using boundary and staircase methods. Fatigue tests were performed in a
      pneumatic cycling machine (2 Hz, 37  degrees C distilled water) for 10 3 and 104
      cycles. Fatigue data were analyzed using an inverse power law relationship and
      log normal-lifetime distribution. Fracture toughness (KIc) was determined using V
      notched specimens (18 *4 *3 mm) and the short beam toughness method (n = 7).
      Vickers hardness (VH) was evaluated (4.9 N, 20 s). Fractographic and EDS analyses
      were also performed. ZLS showed a characteristic strength of 197 MPa, Weibull
      modulus of 4, VH of 6.67 GPa and KIc of 1.93 MPa m1/2. After 103 cycles, for both
      methods, there was a degradation of 78% of the initial strength. There was no
      significant degradation when the number of cycles increased from 103 to 104. Both
      methods resulted in similar Pf and precision at 40 MPa (~50% Pf). Yet, staircase
      shows good accuracy and precision in predicting the stress amplitude for a Pf
      near 50%; while boundary is also effective for Pf lower than 50%. The fatigue
      methods evaluated show similar accuracy and precision for predicting the Pf of a
      glass-ceramic when simulations were made in the range of stress levels and
      lifetimes used in the fatigue tests.

PMID- 30223214
TI  - Recent advances in understanding the fatigue and wear behavior of dental
      composites and ceramics.
AB  - Dental composite and ceramic restorative materials are designed to closely mimic
      the aesthetics and function of natural tooth tissue, and their longevity in the
      oral environment depends to a large degree on their fatigue and wear properties.
      The purpose of this review is to highlight some recent advances in our
      understanding of fatigue and wear mechanisms, and how they contribute to
      restoration failures in the complex oral environment. Overall, fatigue and wear
      processes are found to be closely related, with wear of dental ceramic occlusal
      surfaces providing initiation sites for fatigue failures, and subsurface fatigue
      crack propagation driving key wear mechanisms for composites, ceramics, and
      enamel. Furthermore, both fatigue and wear of composite restorations may be
      important in enabling secondary caries formation, which is the leading cause of
      composite restoration failures. Overall, developing a mechanistic description of
      fatigue, wear, and secondary caries formation, along with understanding the
      interconnectivity of all three processes, are together seen as essential keys to
      successfully using in vitro studies to predict in vivo outcomes and develop
      improved dental restorative materials.

PMID- 30223215
TI  - Mechanical properties, in vitro corrosion resistance and biocompatibility of
      metal injection molded Ti-12Mo alloy for dental applications.
AB  - A biocompatible Ti-12Mo alloy was fabricated by metal injection moulding (MIM)
      using non-spherical titanium, molybdenum powders and a purposely designed binder.
      The density, microstructure and tensile properties were characterized. This was
      followed by a detailed assessment of its in vitro corrosion and biocompatibility
      performances, compared with that of two commonly used titanium-based materials
      extra low interstitial (ELI) Ti-6Al-4V and commercially pure (CP) titanium. The
      MIM-fabricated Ti-12Mo alloy can achieve a wide range of mechanical properties
      through controlling sintering process. Specimens sintered at 1400  degrees C are
      characterized by fairly uniform near-beta microstructure and high relative
      density of 97.6%, leading to the highest tensile strength of 845.3 +/- 21 MPa and
      elongation of 4.15 +/- 0.2% while the highest elastic modulus of 73.2 +/- 5.1
      GPa. Owing to the formation of protective TiO2-MoO3 passive film, the MIM
      fabricated Ti-12Mo alloy exhibits the highest corrosion resistance including the
      noblest corrosion potential, the lowest corrosion current density and the highest
      pitting potential in four different electrolytes. The in vitro cytotoxicity test
      suggests that the MIM-fabricated Ti-12Mo alloy displays no adverse effect on
      MC3T3-E1 cells with cytotoxicity ranking of 0 grade, which is nearly close to ELI
      Ti-6Al-4V or CP Ti. These properties together with its easy net-shape
      manufacturability make Ti-12Mo an attractive new dental implant alloy.

PMID- 30223216
TI  - Eutrophication: A new wine in an old bottle?
AB  - Eutrophication is one of the most common causes of water quality impairment of
      inland and marine waters. Its best-known manifestations are toxic cyanobacteria
      blooms in lakes and waterways and proliferations of green macro algae in coastal
      areas. The term eutrophication is used by both the scientific community and
      public policy-makers, and therefore has a myriad of definitions. The introduction
      by the public authorities of regulations to limit eutrophication is a source of
      tension and debate on the activities identified as contributing or having
      contributed decisively to these phenomena. Debates on the identification of the
      driving factors and risk levels of eutrophication, seeking to guide public
      policies, have led the ministries in charge of the environment and agriculture to
      ask for a joint scientific appraisal to be conducted on the subject. Four French
      research institutes were mandated to produce a critical scientific analysis on
      the latest knowledge of the causes, mechanisms, consequences and predictability
      of eutrophication phenomena. This paper provides the methodology and the main
      findings of this two years exercise involving 40 scientific experts.

PMID- 30223218
TI  - Simultaneous enhancement of nonylphenol biodegradation and short-chain fatty
      acids production in waste activated sludge under acidogenic conditions.
AB  - Nonylphenol (NP) biodegradation in waste activated sludge (WAS) under anaerobic
      conditions is usually slow, and no information on NP biodegradation under
      acidogenic conditions is currently available. In this study, the simultaneous
      enhancement of NP biodegradation and short-chain fatty acids (SCFAs) accumulation
      in a WAS fermentation system under acidogenic conditions was accomplished by
      controlling pH 10 and adding sodium lauryl sulfate (SLS). The biodegradation
      efficiency of NP was found to be 55.5% within 8 d under acidogenic conditions,
      much higher than that in the control (24.6%). Meanwhile, the concentration of
      SCFAs under the same conditions for NP biodegradation was increased from 2234 mg
      COD/L (control) to 4691 mg COD/L (at pH 10 with SLS). Mechanism study revealed
      that the abundances of both NP-degrading microorganisms and acidogenic bacteria
      increased under acidogenic conditions. Altering the enzymatic activity and the
      quantity of functional genes in the acidogenic fermentation system were
      beneficial to NP biodegradation and SCFAs accumulation. Furthermore, organic
      substrates available for uptake by NP-degrading and acidogenic bacteria, i.e. NP,
      protein and carbohydrate, were released from WAS under acidogenic conditions.
      More importantly, intermediate substrates involved in acidogenic fermentation
      were advantageous to the cometabolic biodegradation of NP.

PMID- 30223217
TI  - Effects of potential recirculation on air quality in coastal cities in the
      Yangtze River Delta.
AB  - Air quality is closely related to the synoptic circulation and local wind field
      affecting a certain area as they have distinct influence on the path and speed of
      pollutants. The Yangtze River Delta is located on the eastern coast, and the air
      returning from coastal areas has a detrimental effect on air quality in the area.
      This study proposes to analyze if certain circulation types and the occurrence of
      recirculation are predominantly related to the occurrence of bad air quality in
      the Yangtze River Delta. Using sea level pressure data from 2006 to 2016, we used
      T-mode objective classification to classify circulation in the Yangtze River
      Delta into nine categories. At the same time, using the Allwine and Whiteman (AW)
      method, we categorized local winds in the region as ventilation, stagnation, and
      recirculation types, and we found that the local wind tends to be under
      recirculation conditions when the region was controlled by circulation types 3
      (CT3, southeast low pressure), CT4 (northeast low pressure), CT7 (northwest high
      pressure), and CT8 (north high pressure, south low pressure, with a large
      pressure gradient). By comparing concentrations of pollutants and different local
      wind types, we found that recirculation tended to promote high pollution
      situations. Use of the HYSPLIT (Hybrid Single Particle Lagrangian Integrated
      Trajectory) model to simulate the diffusion of pollutants by recirculation in
      Shanghai in March 2016 confirmed this conclusion. The outputs of HYSPLIT model
      can show the track of air mass intuitively, and then reflect the effect of
      recirculation.

PMID- 30223219
TI  - Nitrogen deposition and decreased precipitation does not change total nitrogen
      uptake in a temperate forest.
AB  - Decreased precipitation and increased anthropogenical by derived nitrogen (N) are
      important climate change factors that alter the availability of soil water and N
      which are crucial to root function and morphological traits. However, these
      factors are seldom explored in forests. To clarify how altered precipitation and
      N addition affect the uptake of organic and inorganic N by fine roots, a field
      hydroponic experiment using brief 15N exposures was conducted in a temperate
      forest in northern China. The root traits related to nutrient foraging (root
      morphology and mycorrhizal colonization) were measured simultaneously. Our
      results showed that all three tree species preferred ammonium (NH4+) over glycine
      and nitrate (NO3-), and NH4+ contributed 73% to the total N uptake from the soil.
      Uptake of glycine was higher than that of NO3-. Decreased precipitation, N
      addition, and their interaction increased NH4+ uptake rate compared with the
      control. Decreased precipitation decreased the glycine and NO3- uptake rate.
      Moreover, N addition, decreased precipitation and their interaction changed root
      morphological traits and significantly decreased mycorrhizal colonization.
      Although our treatments resulted in changes to the root traits and the forms of N
      uptake by plants, the total amount of N uptake did not change among all
      treatments. We conclude that although fine root traits of dominant tree species
      in temperate forests have high plasticity in response to climate change, nutrient
      balance in plants causes the total amount of N uptake to remain unchanged.

PMID- 30223220
TI  - China Act on the Energy Efficiency of Civil Buildings (2008): A decade review.
AB  - China has launched the energy efficiency project (EEP) for its civil building
      sector beginning in the mid-1980s; however, its implementation has not been
      effective. To better promote the EEP for the Chinese civil building sector, the
      Chinese government issued the China Act on the Energy Efficiency of Civil
      Buildings in 2008. This is the first paper to present a review of this act's
      implementation over the past decade. Based on China Database of Building Energy
      Consumption and Carbon Emissions and official documents, the achievements of this
      act are assessed by examining a variety of indicators. The success of the act can
      be attributed to the following factors: 1) a strong and sustained government
      commitment to top policies of building energy efficiency (BEE); 2) extensive
      efforts to apply the BEE standards to newly built civil buildings; 3) various
      incentive schemes involving energy efficiency retrofitting for existing civil
      buildings; 4) the increasing adoption of renewable energy to the civil building
      sector and of systems and platforms of energy efficiency supervision to
      commercial buildings; and 5) the rapid development of green buildings.
      Nevertheless, the revised act must address several challenges in the upcoming
      phase. These challenges mainly include the following: 1) the "double-control"
      strategy for the civil building sector; 2) the substantial development of the EEP
      in rural China; 3) the further development of green buildings for the low-carbon
      civil buildings; 4) the improvement of official statistical data systems on
      energy consumption and carbon emissions for civil buildings; and 5) building
      industrialization and informatization. It's expected that our efforts as
      constituting significant guidance for evaluating the EEP in the Chinese civil
      building sector, and the efforts will also be treated as an example for other
      developing countries to evaluate and revise their BEE acts.

PMID- 30223221
TI  - Agriculture, diversions, and drought shrinking Galilee Sea.
AB  - In water-limited regions worldwide, climate change and population growth threaten
      to desiccate lakes. As these lakes disappear, water managers have often
      implicated climate change-induced decreases in precipitation and higher
      temperature-driven evaporative demand-factors out of their control, while
      simultaneously constructing dams and drilling new wells into aquifers to permit
      agricultural expansion. One such shrinking lake is the Sea of Galilee (Lake
      Kinneret), whose decadal mean level has reached a record low, which has sparked
      heated debate regarding the causes of this shrinkage. However, the relative
      importance of climatic change, agricultural consumption, and increases in
      Lebanese water consumption, remain unknown. Here we show that the level of the
      Sea of Galilee would be stable, even in the face of decreasing precipitation in
      the Golan Heights. Climatic factors alone are inadequate to explain the record
      shrinkage of the Sea of Galilee. We found no decreasing trends in inflow from the
      headwaters of the Upper Jordan River located primarily in Lebanon. Rather, the
      decrease in discharge of the Upper Jordan River corresponded to a period of
      expanding irrigated agriculture, doubling of groundwater pumping rates within the
      basin, and increasing of the area of standing and impounded waters. While rising
      temperatures in the basin are statistically significant and may increase
      evapotranspiration, these temperature changes are too small to explain the
      magnitude of observed streamflow decreases. The results demonstrate that
      restoring the level of the Sea of Galilee will require reductions in groundwater
      pumping, surface water diversions, and water consumption by irrigated
      agriculture.

PMID- 30223222
TI  - Mechanism of plant mediated methane emission in tropical lowland rice.
AB  - Methane (CH4) is predominantly produced in lowland rice soil, but its emission
      from soil to atmosphere primarily depends on passage/conduit or capillary pore
      spaces present in rice plants. The gas transport mechanism through aerenchyma
      pore spaces of rice cultivars was studied to explore the plant mediated CH4
      emission. Seven rice cultivars, based on the life cycle duration (LCD), were
      tested in tropical eastern India. Three LCD groups were, (a) Kalinga 1 and CR
      Dhan 204 (LCD: 110-120 days); (b) Lalat, Pooja and CR 1014 (LCD: 130-150 days);
      and (c) Durga and Varshadhan (LCD: 160-170 days). Rate of CH4emission, root
      exudates, root oxidase activities and shoot aerenchyma pore spaces were analyzed
      to study the mechanism of plant mediated emission from rice. Aerenchyma pore
      space was quantified in the hypothesis that it regulates the CH4 transportation
      from soil to atmosphere. The ratio of pore space area to total space was lowest
      in Kalinga 1 cultivar (0.29) and highest was in Varshadhan (0.43). Significant
      variations in the methane emission were observed among the cultivars with an
      average emission rate ranged from 0.86 mg m-2 h-1 to 4.96 mg m-2 h-1. The CH4
      emission rates were lowest in short duration cultivars followed by medium and
      long duration ones. The greenhouse gas intensity considering average CH4 emission
      rate per unit grain yield was also lowest (0.35) in Kalinga 1 and relatively less
      in short and medium duration cultivars. Root exudation was higher at panicle
      initiation (PI) than maximum tillering (MT) stage. Lowest exudation was noticed
      in (197.2 mg C plant-1 day-1) Kalinga 1 and highest in Varsadhan (231.7 mg C
      plant-1 day-1). So we can say, the rate of CH4 emission was controlled by
      aerenchyma orientation, root exudation and biomass production rate which are the
      key specific traits of a cultivar. Identified traits were closely associated with
      duration and adaptability to cultivars grown in specific ecology. Therefore,
      there is possibility to breed rice cultivars depending on ecology, duration and
      having less CH4 emission potential, which could be effectively used in greenhouse
      gas mitigation strategies.

PMID- 30223223
TI  - CryoEM of bacterial secretion systems.
AB  - The need for bacteria to interact with their environment has driven the evolution
      of elaborate secretion systems. By virtue of their function, secretion systems
      are macromolecular complexes associated with the cell envelope and therefore
      inherently difficult to study by conventional structural biology techniques. Cryo
      electron microscopy (cryoEM) has become an invaluable technique to study large
      membrane-embedded complexes and led to major advances in the mechanistic
      understanding of secretion systems. CryoEM comprises of two main modalities,
      namely single particle analysis and tomography. Here, we review how detailed
      structures retrieved by single particle analysis combine elegantly with
      tomography experiments in which the secretion systems are observed in their
      native cellular context.

PMID- 30223224
TI  - Image-guided tumour biopsies in a prospective molecular triage study (MOSCATO
      01): What are the real risks?
AB  - PURPOSE: To evaluate efficacy, complications and preprocedural risk factors for
      percutaneous image-guided core needle biopsy of malignant tumours for genomic
      tumour analysis. MATERIALS AND METHODS: Procedural data for core biopsies
      performed at a single centre for the MOSCATO-01 clinical trial were prospectively
      recorded between December 2011 and March 2016. Data assessed included patient
      demographics, tumour characteristics, procedural outcomes and complications.
      RESULTS: A total of 877 biopsies were performed under computed tomography (38.4%)
      or ultrasound guidance (61.6%) for tumours in the liver (n = 363), lungs (n =
      229), lymph nodes (n = 138), bones (n = 15) and other miscellaneous sites (n =
      124). Each biopsy harvested a mean 4.4 samples [1-15], with adequate tumour yield
      for genomic analysis in 95.3% of cases. Procedural complications occurred in 89
      cases (10.1%), with minor grade I complications in 59 (66.3%); grade II in 16
      (18%) and grade III in 14 (15.7%). No grade IV complications and no procedure
      related death occurred. The most common complications were pneumothorax (51/89,
      57.3%), haemorrhage (24/89, 27%) and pain (8/89, 8.9%). Predictive factors for
      complications by univariate analysis included biopsied organ (lung vs other),
      sample number, prone position, lesion size, lesion depth and biopsy approach. By
      multivariate analysis, only pulmonary biopsy was a significant risk factor (odds
      ratio = 27.23 [4.93-242.76], p < 0.01). CONCLUSION: Percutaneous image-guided
      core needle biopsy in cancer patients provides an effective method to obtain
      molecular screening samples, with an overall low complication rate. Lung mass
      biopsies present a higher risk of complication, although complications are
      manageable by minimally invasive techniques without prolonged sequelae.

PMID- 30223225
TI  - Addressing heterogeneity in the design of phase II clinical trials in geriatric
      oncology.
AB  - INTRODUCTION: Cancer in the elderly is a major public issue. However, older
      patients have long been debarred from clinical trials. There is a high unmet
      medical need for specific trials addressing oncology strategies adapted to older
      patients' conditions. While randomised phase III trials remain the gold standard,
      they usually require large numbers of patients. In this perspective, late single
      arm phase II trials assessing treatment feasibility might prove a good
      alternative. However, it is essential to take into account the heterogeneity in
      an ageing population characterised by frailty. Standard parallel phase II studies
      in defined frail and non-frail populations also require a high number of
      patients. Used in molecular subtyping and treatment effect heterogeneity,
      stratified adaptive designs can improve statistical performance, but they have
      never been used in geriatric oncology. This report describes their potential
      benefits and useful applications as compared with standard designs. METHODS: In a
      heterogeneous population, stratified adaptive designs allowed us to select
      subgroups of interest in two stages. Operational characteristics were evaluated
      through simulations of clinical trials under different scenarios. RESULTS:
      Simulations showed that the use of stratified adaptive designs can efficiently
      minimise both the number of patients to be included and accrual duration with
      competitive statistical power and high heterogeneity detection rate at interim
      analysis. CONCLUSION: Compared with classical phase II designs, stratified
      adaptive phase II trial methodology offers a promising approach to improve
      clinical research in geriatric oncology. These designs may also be efficient in
      other populations such as children or adolescents and young adults.

PMID- 30223226
TI  - Fulvestrant plus goserelin versus anastrozole plus goserelin versus goserelin
      alone for hormone receptor-positive, HER2-negative tamoxifen-pretreated
      premenopausal women with recurrent or metastatic breast cancer (KCSG BR10-04): a
      multicentre, open-label, three-arm, randomised phase II trial (FLAG study).
AB  - BACKGROUND: We investigated the efficacy and safety of fulvestrant plus goserelin
      (F + G) versus anastrozole plus goserelin (A + G) in comparison with goserelin
      (G) alone in premenopausal women with hormone receptor-positive (HR+), human
      epidermal growth factor receptor 2-negative (HER2-), tamoxifen-pretreated
      metastatic breast cancer (MBC). PATIENTS AND METHODS: In this multicentre, open
      label, randomised phase II study, premenopausal women aged >=18 years with HR+,
      HER2-, tamoxifen-pretreated MBC were randomly assigned (1:1:1) to F + G, A + G or
      G alone. The primary end-point was time to progression (TTP). Secondary end
      points included overall survival, overall response rate, clinical benefit rate
      and toxicity. RESULTS: Of 138 eligible patients, 44 were randomly assigned to
      receive F + G, 47 to A + G and 47 to G alone. The median follow-up duration was
      32.2 months (interquartile range: 23.69-40.86) and the median age was 43.0 years
      (range 23.0-55.0). The median TTP was 16.3 months (95% confidence interval [CI]
      7.5-25.1) for F + G, 14.5 months (95% CI 11.0-18.0) for A + G and 13.5 months
      (95% CI 10.3-16.8) for G alone. Compared with G alone, the hazard ratios were
      0.608 for F + G (95% CI, 0.370-0.998; p = 0.049) and 0.982 for A + G (95% CI,
      0.624-1.546; p = 0.937). In terms of visceral metastasis, a stratification
      factor, there were no TTP differences according to treatment arm. Grade III or IV
      toxicities were rarely observed. Of the common adverse events, grade I arthralgia
      and joint stiffness were more frequently observed in the F + G than in the A + G
      or G-alone groups (p < 0.05, respectively). CONCLUSIONS: F + G provides a
      promising new option for the treatment of premenopausal women with HR+, HER2-,
      tamoxifen-pretreated MBC. TRIAL REGISTRATION: ClinicalTrials.gov number
      NCT01266213 and Korean Cancer Study Group (KCSG) Breast cancer protocol number
      BR10-04.

PMID- 30223227
TI  - Patient-assisted compression helps for image quality reduction dose and improves
      patient experience in mammography.
AB  - We evaluated the impact of patient-assisted compression (PAC) on image quality,
      dose, workflow and patient experience of mammography. Patients aged 40-90 years
      coming for bilateral mammography were included prospectively in the study. After
      positioning each breast, the technologist performed the compression and exposure
      of the first breast, initiated the compression of the other until 3 daN and then
      let the patient complete the compression using a remote control device. Image
      quality, compression force, breast thickness, average glandular dose and pain
      value for each breast were assessed for PAC and technologist compression (TC).
      The compression level was significantly higher with PAC than TC for both
      craniocaudal (CC; median difference 2.0 daN, p < 0.0001) and mediolateral oblique
      (MLO) views (median difference 1.5 daN, p < 0.0001). Breast thickness was reduced
      with PAC (CC, median difference -1.90 cm, p = 0.02), as well as glandular dose
      (CC, median difference -0.03, p = 0.02). The image quality was rated equivalent
      for both modes in 85% (85/100) of cases, superior for PAC in 10% (10/100) of
      cases and inferior in 5% (5/100) of cases. There was no significant difference in
      discomfort or pain felt between PAC and TC modes. Seventy-four percent of
      patients reported that the self-compressing device would facilitate their
      reattendance. PAC may be a suitable technique for mammography examinations,
      providing an equivalent image quality to TC. Moreover, as the breast compression
      level is increased, PAC may help reduce breast thickness, hence glandular dose.
      The fact that patients have control over the procedure may change their
      perception of mammography and improve uptake and compliance.

PMID- 30223228
TI  - Static postural control disturbances among the different multiple sclerosis
      phenotypes: A Neurocom Balance Manager(r) evaluation study.
AB  - BACKGROUND: The computerized stabilometric platform can be used and privileged
      over clinical scales, as self-administered questionnaires to asses postural
      control and balance evaluation in Multiple sclerosis (MS). Aim of our study was
      to evaluate static postural control assessed by Neurocom Balance Manager(r)
      through the modified Clinical Test of Sensory Interaction on Balance (mCTSIB) in
      relapsing-remitting MS (RRMS), progressive MS (PMS) and CIS, compared to healthy
      controls (HC). METHODS: We screened MS patients consecutively referring to our MS
      Center at University of Catania, during July 2013-June 2014 diagnosed as CIS,
      RRMS and PMS. All MS patients underwent clinical and neurological evaluations and
      a complete postural exam by Neurocom Balance Manager(r) in order to evaluate
      Center of Pressure (COP), through mCTSIB. We evaluated the following parameters:
      Total Path Length-open eyes (TPL-OE), Total Path Length-closed eyes (TPL-CE),
      Sway Area-open eyes (SA-OE), Sway Area-closed eyes (SA-CE), Mean sway velocity
      open eyes (MSV-OE), Mean sway velocity-closed eyes (MSV-CE). Additionally,
      patients were tested by Berg balance scale (BBS) for balance and Barthel Index
      (BI) for disability outcomes. RESULTS: Out of 170 MS patients assessed for
      eligibility, 163 met the inclusion/exclusion criteria and were finally enrolled.
      All balance parameters were found more impaired in MS group compared to controls
      and CIS. Moreover, no differences in terms of balance assessment were found
      between HC and CIS. The correlation analysis showed that BBS was strongly
      associated to SA-OE, SA-CE, TPL-OE and MSV-OE. We also found a correlation
      between BI and SA-CE. CONCLUSION: Our study revealed significant differences
      among HCs, CIS and MS. MS, especially PMS, exhibit the worst balance performances
      especially in EC trials. The higher correlation between balance parameters,
      especially sway area, and BBS score confirmed the reliability and sensibility of
      mCTSIB assessment in evaluating static postural control in MS patients.

PMID- 30223229
TI  - Serum sickness (Like Reaction) in a patient treated with alemtuzumab for multiple
      sclerosis: A case report.
AB  - BACKGROUND: Alemtuzumab is a monoclonal antibody approved for relapsing-remitting
      multiple sclerosis (RRMS). The only report of Serum Sickness (SS) in a MS patient
      occurred during treatment with natalizumab. Non-protein drugs, such as some
      antibiotics, may induce "SS-like" reactions (SSLR), whose clinical and laboratory
      features may partially overlap with the traditional SS. OBJECTIVE: To report a
      case of SS/SSLR in a RRMS patient treated with alemtuzumab. CASE REPORT: A 42
      year-old-woman with RRMS developed SS/SSLR in the first week after the first
      alemtuzumab treatment. Concomitant medications included trimethoprim
      sulfamethoxazole at low dose. Intravenous methylprednisolone therapy led to
      clinical resolution and normalization of serum inflammatory markers. CONCLUSION:
      SS/SSLR should be considered in patients treated with alemtuzumab developing
      delayed fever, rash and arthralgia and differentiated with Infusion Associated
      Reactions (IARs) and infections.

PMID- 30223230
TI  - Photophobia in multiple sclerosis.
AB  - BACKGROUND: Photophobia has never been investigated in MS. METHODS: In this pilot
      study we used photosensitivity questionnaire assessment (PAQ) to evaluate
      tolerability to light in 73 MS patients and 62 healthy controls. RESULTS: We
      identified a lower PAQ score and a higher number of photophobic subjects in MS
      than in controls. Moreover, clinical disability or previous optic neuritis did
      not predict the photosensitivity profile. CONCLUSION: Further studies to
      investigate the pathophysiological mechanisms underlying photophobia in MS are
      needed.

PMID- 30223231
TI  - Multiple Sclerosis: kFLC index values related to gender.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic multifactorial inflammatory and
      neurodegenerative disease of the central nervous system (CNS). The identification
      of biomarkers with good diagnostic and prognostic power is of great importance
      for monitoring and treating MS patients. METHODS: We analyzed serum and
      cerebrospinal fluid of 228 patients, with different neurological disorders and
      with MS to confirm our previous results and determine a possible gender
      difference of kFLC Index cut-off. RESULTS: We have obtained a kFLC Index cut-off
      of 12.5 (100% specificity and 90.4% sensitivity) and 11 (100% specificity and
      97.5% sensitivity) for women and men with MS respectively. CONCLUSIONS: This
      study reinforces the importance that kFLC Index could have as a diagnostic aid to
      detect MS. Our data highlight a difference in the cut-off of the kFLC Index
      calculated by gender; male patients with a kFLC Index value greater than 11 are
      at higher risk to develop MS respect females having the same result.

PMID- 30223232
TI  - Violent deaths of pregnant women in Egyptian governorates of Cairo and Giza.
AB  - BACKGROUND: Pregnancy-associated deaths are a widely recognized phenomenon, that
      warrants in-depth investigation. Of the 319 suspicious deaths of adult women (>20
      years) autopsied during 2011-2012, in the Cairo and Giza governorates, 37 (11.7%)
      women were pregnant at the time of the autopsy. This paper analyzes the
      corresponding demographic data, autopsy findings, and toxicological screening.
      THE RESULTS: Reveal that the number of deaths of pregnant women were higher in
      2012 than in 2011. In addition, the number of cases from Giza exceeded those from
      Cairo (62.2% and 37.8%, respectively). Most cases involved married women (62.2%)
      in the third trimester of pregnancy (67.5%). Most deaths were predominantly un
      intentional (51.4%) attributed to peri-partum complications. Homicidal deaths
      contributed to 43% of cases, and the husband was the suspect perpetrator in 37.5%
      of cases. Only two cases were associated with substance abuse. CONCLUSION: the
      paper concludes that this analysis may inform future strategies to protect
      pregnant women from the hazards of violence and labor that threaten their lives.

PMID- 30223233
TI  - Partially hydrolyzed formula in non-exclusively breastfed infants: A systematic
      review and expert consensus.
AB  - OBJECTIVES: Guidance and evidence supporting routine use of partially hydrolyzed
      formula (pHF) versus intact cows' milk protein (CMP) formula are limited in non
      exclusively breastfed infants. The aim of this review was to better clarify
      issues of routine use of pHF in non-exclusively breastfed infants who are not at
      risk for allergic disease by using a systematic review and Delphi Panel
      consensus. METHODS: A systematic review and Delphi consensus panel (consisting of
      eight8 international pediatric allergists and gastroenterologists) was conducted
      to evaluate evidence supporting growth, tolerability, and effectiveness of pHF in
      non-exclusively breastfed infants. RESULTS: None of the studies reviewed
      identified potential harm of pHF use compared with CMP in non-exclusively
      breastfed infants. There was an expert consensus that pHF use is likely as safe
      as intact CMP formula, given studies suggesting these have comparable nutritional
      parameters. No high-quality studies were identified evaluating the use of pHF to
      prevent allergic disease in non-exclusively breastfed infants who are not at risk
      for allergic disease (e.g., lacking a parental history of allergy). Limited data
      suggest that pHF use in non-exclusively breastfed infants may be associated with
      improved gastric emptying, decreased colic incidence, and other common functional
      gastrointestinal symptoms compared with CMP. However, because the data are of
      insufficient quality, the findings from these studies have to be taken with
      caution. No studies were identified that directly compared the different types of
      pHF, but there was an expert consensus that growth, allergenicity, tolerability,
      effectiveness, and clinical role among such pHF products may differ. CONCLUSIONS:
      Limited data exist evaluating routine use of pHFs in non-exclusively breastfed
      infants, with no contraindications identified in the systematic review. An expert
      consensus considers pHFs for which data were available to be as safe as CMP
      formula as growth is normal. The preventive effect on allergy of pHF in infants
      who are not at risk for allergic disease has been poorly studied. Cost of pHF
      versus starter formula with intact protein differs from country to country.
      However, further studies in larger populations are needed to clinically confirm
      the benefits of routine use of pHF in non-exclusively breastfed infants. These
      studies should also address potential consumer preference bias.

PMID- 30223234
TI  - Eccentric cross-exercise after anterior cruciate ligament reconstruction: Novel
      case series to enhance neuroplasticity.
AB  - OBJECTIVES: Substantial changes in neural function are historically present after
      anterior cruciate ligament reconstruction (ACLR), and are not rectified with
      traditional rehabilitation. Cross-exercise is a potential means to enhance neural
      excitability and improve recovery after ACLR. Hence our purpose, was to detail
      changes in brain activation, neural excitability and patient-reported outcomes in
      a cohort that completed an 8-week quadriceps-focused eccentric cross-exercise
      training program immediately following ACLR. DESIGN: Case series. SETTING:
      University. PARTICPANTS: Five patients participated in an 8-week (24-session)
      eccentric cross-exercise intervention after ACLR. MAIN OUTCOME MEASURES: Brain
      activation, neural activity and patient-reported outcomes were evaluated within 2
      weeks post-ACLR and again at 10-weeks post-ACLR after the intervention. Each
      cross-exercise session consisted of 4 sets of 10 isokinetic eccentric
      contractions at 60 deg/sec with the noninvolved limb. RESULTS: Following the
      intervention, patients demonstrated a facilitated spinal reflexive and muscle
      activity response from the motor cortex during a time when these measures are
      known to be depressed. Patients also demonstrated a reduce dependence on frontal
      cortex activity to generate quadriceps contractions. Further patients reported
      significant reductions in pain and symptoms and greater knee function.
      CONCLUSIONS: Eccentric cross-exercise after ACLR helps to facilitate positive
      adaptations in neural function and patient reported outcomes.

PMID- 30223235
TI  - Comparison of the effects of sensorimotor training programs on pain,
      electromyography and kinematics in patients with scapular downward rotation
      syndrome.
AB  - OBJECTIVES: Comparison of the effects of six weeks sensorimotor and sensorimotor
      with passive interventions programs on pain, electromyography (EMG) and
      kinematics in patients with scapular downward rotation syndrome (SDRS). DESIGN:
      Randomized Controlled Trial. SETTING: Institutional practice. PARTICIPANTS: 140
      active subjects with unilateral SDRS were randomized to three groups. Group one
      received sensorimotor (n = 46), group two received sensorimotor with passive
      interventions (n = 48), and group three received active self-exercise as a
      control group (n = 46). Pain, EMG of the levator scapula (LS), upper trapezius
      (UT), lower trapezius (LT), and serratus anterior (SA), as well as kinematics
      were measured at the baseline and after the interventions. MAIN OUTCOME MEASURES:
      Primary outcome: Pain - Secondary outcomes: EMG and kinematics. RESULTS: There
      were significant between-group differences between intervention groups one and
      two in pain, LS and SA onset activation favoring group two and LS muscle activity
      favoring group one. There were significant within-group changes in almost all
      dependent variables except LT muscle onset activation in both groups one and two.
      CONCLUSIONS: The addition of passive interventions on the scapula and neck may be
      superior to conservative training alone on the scapula and neck for improving
      neck pain, EMG and kinematics in participants with SDRS.

PMID- 30223236
TI  - Differentiating motives for nonmedical prescription stimulant use by personality
      characteristics.
AB  - Nonmedical prescription stimulant use (NPS) is increasing, particularly among
      college students. College students typically engage in NPS for cognitive
      enhancement, recreational, and appetite/weight-related purposes; however, little
      research has used these motives to identify specific risk for, or consequences
      of, NPS. Moreover, there may be unique risk factors for motive-specific NPS that
      have yet to be explored, such as relevant personality traits (i.e., distress
      tolerance, impulsivity, and perfectionism) that are associated with NPS in
      general. Therefore, this study aimed to examine whether NPS users and nonusers
      could be differentiated via facets of impulsivity, perfectionism, and distress
      tolerance, and whether users could be further differentiated by reported motive
      for use based on these traits. Midwestern university undergraduate students (N =
      668) who were enrolled in a psychology research pool completed an online survey
      assessing demographics, NPS and motives, and measures of distress tolerance,
      impulsivity, and perfectionism. Participants were primarily female (78%) and aged
      18-54 (M = 20.10, SD = 3.19) years. Univariate and multivariate analysis of
      variance tests revealed associations between lifetime NPS and higher impulsivity,
      higher perfectionism, and lower distress tolerance. Further tests revealed NPS
      for appetite/weight-related purposes was associated with lower distress
      tolerance, while NPS for recreational purposes was associated with higher
      impulsivity. These findings contribute novel information regarding NPS motives
      and personality constructs. This information may aid in comprehensive
      identification of high-risk individuals for NPS and inform the development of
      specialized prevention and intervention efforts.

PMID- 30223237
TI  - Falls Efficacy Scale-International: Exploring psychometric properties with adult
      day care users.
AB  - The majority of validation studies with the Falls Efficacy Scale-International
      (FES-I) are conducted with independent community-dwelling older people, which
      limits extrapolation to more vulnerable people, namely those receiving adult day
      care services. This study aimed to analyse the psychometric properties of the FES
      I in terms of internal consistency, test-retest reliability, concurrent and
      convergent validity with users of adult day care centres. A cross-sectional study
      was conducted. Data collection included a socio-demographic questionnaire, the
      FES-I, the Activities-specific Balance Confidence Scale (ABC), the Hospital
      Anxiety and Depression Scale (HADS), the Timed Up and Go test (TUG) and the Five
      Times Sit to Stand Test (FTSST). Descriptive and inferential analyses were
      performed. A total of 100 users of adult day care centres (81.94 +/- 6.43 years
      old; 77% female) have participated. The FES-I had excellent internal consistency
      (alpha = 0.970) and test-retest reliability (ICC2,1 = 0.979). A significant
      negative correlation was found between the FES-I and the ABC (rs = -0.828; p <
      0.001), suggesting good concurrent validity. FES-I scores were significantly
      higher among those who were female, had less educational levels and reported
      having fear of falling. Significant correlations were found between FES-I and age
      (rs = 0.217; p < 0.05), HADS-Anxiety (rs = 0.486; p < 0.001), HADS-Depression (rs
      = 0.658; p < 0.001), TUG (rs = 0.653; p < 0.001) and FTSST (rs = 0.635; p <
      0.001), indicating acceptable convergent validity. The FES-I is a reliable and
      valid instrument to assess concern about falling among users of adult day care
      centres. The findings are highly comparable with those previously found for non
      users. FES-I can be used to prevent risk of falls in this type of care settings.

PMID- 30223238
TI  - Executive functions, selective attention and information processing in patients
      with obsessive compulsive disorder: A study from west of Iran.
AB  - Obsessive-compulsive disorder (OCD) is associated with cognitive dysfunction.
      Deeper and wider knowledge of the cognitive components of these patients can play
      an important role in better understanding of this disorder. This study aimed to
      compare executive function, selective attention and information processing in OCD
      patients and healthy controls. The current study was performed on 54 patients
      meeting DSM-5 criteria for OCD and 54 healthy subjects who matched with patients
      in gender, age, marital and educational status. The cognitive functions were
      assessed by The Stroop test, Wisconsin Cart Sorting Test (WCST), Paced Auditory
      Serial Addition Test (PASAT) and the Yale-Brown Obsessive-Compulsive Scale (Y
      BOCS). The performance of the OCD group was significantly worse than the healthy
      group in comparison with the all subscales of the Stroop and WSCT tests. Also,
      functions in information processing among two groups were statistically
      significant for 3- and 2-second PASAT. The results demonstrated that OCD patients
      have deficits in several aspects of cognitive functions. Hence, the treatment of
      these patients can be contributed by paying more attention to these deficits.

PMID- 30223239
TI  - Interaction of CuO nanoparticles with duckweed (Lemna minor. L): Uptake,
      distribution and ROS production sites.
AB  - CuO engineered nanoparticles (NPs) are of increasing concern due to their
      extensive use in daily life and adverse effect on aquatic organisms. The
      investigations on the toxicity of CuO NPs to aquatic plants through uptake from
      roots versus fronds are limited. This paper discusses the interactions of CuO NPs
      with Lemna minor, a floating plant. After CuO NPs (150 MUg L-1) exposure for 7
      days, the frond number, frond surface area and dry weights of whole plants
      significantly decreased by 32%, 47% and 33%; the responses were dose-dependent.
      Microscopy imaging showed that the epidermis was severely damaged in fronds,
      edges were severely sloughed off and cell integrity was damaged in roots.
      Shrinkage of both chloroplast and starch grains were observed in the frond cells.
      Internalization of CuO NPs in root and frond cells during CuO NPs (1 mg L-1)
      exposure was confirmed with the root Cu levels of Lemna minor being three times
      higher than the fronds by using transmission electron microscopy and flame atomic
      absorption spectrophotometry. Reactive oxygen species, mainly H2O2 (increased by
      56%) and .OH (increased by 57%), accumulated in Lemna minor tissues in response
      to CuO NPs exposure. Moreover, chloroplasts were confirmed as a site of ROS
      production. These findings are helpful for better understanding the biological
      responses of aquatic plants upon NPs exposure.

PMID- 30223240
TI  - Recovery of phosphorus rich krill shell biowaste for uranium immobilization: A
      study of sorption behavior, surface reaction, and phase transformation.
AB  - Increased generation of shrimp shell from exploitation of krill results in
      emerging biowaste pollution, in addition, uranium pollution has drawn public
      concern due to the rapid development of nuclear power, uranium mining, and
      nuclear fuel processing. In this study, krill shells were recovered and used as a
      potential natural biosorbent for uranium immobilization, thereby enabling both
      uranium decontamination and krill shell reutilization. Interaction of uranium
      with krill shell surface and their transformation were investigated by using
      batch sorption experiments, scanning electron microscopy, and transmission
      electron microscopy. Krill shell had high uranium sorption ability. Uranium was
      transformed into a nano-scale precipitate. The mapping of phosphorus and uranium
      was related to the nano-scale precipitate, indicating that sorption of uranium
      was dependent on phosphorus. Surface chemisorption between phosphate in krill
      shell and uranium as well as the formation of the nano-scale precipitate were
      interpreted as the mechanism of uranium immobilization. Thus, natural krill shell
      waste has potential for extensive use as a promising and cost-effective sorbent
      for uranium immobilization and krill shell reutilization.

PMID- 30223241
TI  - A circular toxicity approach to isoprostanes: From markers of oxidative stress,
      to epidemiological warning systems and agents of aquatic toxicity.
AB  - Isoprostanes (IsoPs) are a class of oxidation products naturally formed in vivo
      that are indicative of endogenous oxidative stress. In individuals with chronic
      and oxidative stress related diseases, IsoPs are increased to pathological
      levels. Since they are excreted through urine into sewage systems, IsoPs can be
      detected in wastewater treatment plants' (WWTPs) effluents and thus can be used
      to evaluate the health status of a given population. The underlying principle is
      that higher isoprostanes WWTPs' levels correspond to populations undergoing
      higher levels of oxidative stress, and thus disease. However, IsoPs are not
      eliminated by WWTPs and will end up being released into the aquatic environment,
      where they will be available for uptake by aquatic species. Being bioactive
      molecules, it has been suggested that IsoPs in the environment may elicit
      oxidative stress in aquatic organisms. In this context, we have critically
      reviewed the available data on IsoPs as products and effectors of toxicity, and
      propose the new concept of "circular toxicity". In general, IsoPs excreted by
      humans as a consequence of oxidative stress are released into the aquatic
      environment where they may interact with aquatic organisms and induce the
      production of more IsoPs. These stress markers, in turn, will also be excreted,
      increasing the already high levels of stressors in the aquatic environment and
      thus create an escalating cycle of oxidative stress.

PMID- 30223242
TI  - Identification of novel genes involved in gingival epithelial cells responding to
      Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis infections.
AB  - OBJECTIVE: This study aimed to identify the differentially expressed genes (DEGs)
      in gingiva epithelial cells responding to Aggregatibacter actinomycetemcomitans
      and Porphyromonas gingivalis infections using bioinformatics method. STUDY
      DESIGN: GSE9723 dataset was downloaded from Gene Expression Omnibus, and DEGs
      between the infected cells and controls were identified using unpaired t-test.
      Overlapping DEGs in responding to Aggregatibacter actinomycetemcomitans and
      Porphyromonas gingivalis infections were extracted. Protein-protein interaction
      networks were constructed and functional modules were isolated using Molecular
      Complex Detection algorithm. Key genes in protein-protein interaction network and
      Molecular Complex Detection modules were subjected to functional enrichment
      analyses. In addition, the transcriptional factors were predicted. RESULTS: A
      total of 533 co-up-regulated and 202 co-down-regulated genes were identified. The
      up-regulated genes, including IL6, CCL19, EDN1, ADCY9, and BCL2 and the down
      regulated genes, including CCNB1, PLK1, and CCNA2 were the key genes in the
      protein-protein interaction network and modules. They were intensively enriched
      in chemokine signaling pathway, calcium signaling pathway and cell cycle.
      Finally, two transcriptional factors, E12 and NRSF, targeting to the up-regulated
      genes and one transcriptional factor, NRP1, targeting the down-regulated genes,
      were predicted. CONCLUSIONS: CCNB1, PLK1, and CCNA2 might play important roles in
      the response of host epithelial cells to Aggregatibacter actinomycetemcomitans
      and Porphyromonas gingivalis.

PMID- 30223243
TI  - Dual disassembly and biological evaluation of enzyme/oxidation-responsive
      polyester-based nanoparticulates for tumor-targeting delivery.
AB  - Polyester-based nanoparticulates (NPs) are ideal nanocarriers for intracellular
      delivery of anticancer drugs because of their biocompatibility. However, an on
      going challenge is the controlled and enhanced release of encapsulated
      therapeutics in response to unique changes that occur within cancer cells.
      Herein, we report the versatility of dual responses to enzymatic and oxidative
      reactions found in cancer cells toward the development of polyester-NPs as
      effective tumor-targeting intracellular nanocarriers. A facile nanoprecipitation
      method allows for the preparation of hydrophobic cores composed of novel
      polyester designed with esterase-responsive ester groups and oxidation-responsive
      sulfide linkages on their backbones, physically stabilized with poly(ethylene
      glycol)-based polymeric shells. The formed core/shell-type NPs with a diameter of
      120 nm exhibit excellent colloidal stability in physiological conditions and in
      the presence of serum proteins. When exposed to esterase and hydrogen peroxide,
      NP integrity is disrupted, leading to the enhanced release of encapsulated
      doxorubicin, confirmed by dynamic light scattering and spectroscopic analysis.
      Combined results from epifluorescence microscopy, confocal laser scanning
      microscopy, flow cytometry, and cell viability demonstrate that doxorubicin
      loaded NPs reveal rapid penetration and enhanced intracellular release of
      doxorubicin, thus inhibiting tumor progression. Importantly, the cellular uptake
      of doxorubicin-loaded core/shell NPs primarily via caveolae-dependent mechanism
      promotes their use in targeting a broad spectrum of cancers.

PMID- 30223244
TI  - Polydopamine particles as nontoxic, blood compatible, antioxidant and drug
      delivery materials.
AB  - Herein, the potential biomedical application of poly(3,4
      dihyroxyphenyl)ethylamine, (poly(dopamine)-p(DA)) particles is reported. P(DA)
      particles with the size about 100 nm, 18.05 m2/g specific surface area, and
      mesoporous structure (7.19 nm pore width) were prepared and shown to be
      chemically modifiable using chlorosulfonic acid (CSA) and 3-CHloro-2
      hydroxypropyl) trimethylammonium chloride solution (CHPACl) to obtain sulfonic
      acid and quaternary amine group containing modified p(DA) particles, m-p(DA)-CSA
      and m-p(DA)-CHPACl particles, respectively. The hydrolytic degradation of p(DA)
      particles at different pHs, including 1, 7.4 and 11, was carried out at 37.5 
      degrees C. These degradation studies revealed that p(DA) is slightly degradable
      at pH 1 and pH 7.4 with weight losses of 13.01 +/- 0.08% and 7.26 +/- 0.23% in 11
      days, respectively. At pH 11, a sustained degradation that is almost linear
      degradation with time was observed for up to 30 days, with a total weight loss of
      21.42 +/- 0.88%. Furthermore, p(DA) particles were tested for cell toxicity
      against COS-1 cells and found non-toxic up to 50 MUg/mL with 95.6 +/- 4.5% cell
      viability as compared to 37.5 +/- 0.03% for DA molecules. The p(DA) particles and
      DA were also compared for their ability to inhibit alpha-glucosidase; both
      inhibited alpha-glucosidase inhibition activity a concentration-dependent
      fashion: at concentrations of 500-4000 MUg/mL, p(DA) provided 8.52-27.67%
      inhibition while DA inhibited 42.8-67.7% over the same concentration range.
      Furthermore, p(DA) particles were found to be blood compatible e.g., non
      hemolytic with 1.87 +/- 0.97% hemolysis ratio up to 50 MUg/mL concentration and
      with 86.7% blood clotting index. Interestingly, p(DA) particle can be considered
      as an effective antioxidant with 33.5 +/- 3.9 MUg/ mL total phenol content in
      terms of gallic acid equivalency and 0.89 +/- 0. 30 MUmol/g trolox equivalent
      antioxidant capacity (TEAC). Finally, p(DA) particles and their modified forms, m
      p(DA)-CSA, and m-p(DA)-CHPACl, were shown to be useful as active agent/drug
      delivery devices by using acyclovir as a model drug that can be readily loaded
      into particles and released at longer times at higher amounts for the modified
      p(DA) particles at physiological conditions.

PMID- 30223245
TI  - Poly(silsesquioxanes) and poly(siloxanes) grafted with N-acetylcysteine for
      eradicating mature bacterial biofilms in water environment.
AB  - Bacteria adapt to their living environment forming organised biofilms. The
      survival strategy makes them more resistant to disinfectants, which results in
      acute biofilm-caused infections, secondary water pollution by biofilm metabolites
      and bio-corrosion. New, efficient and environmentally friendly strategies must be
      developed to solve this problem. Water soluble N-acetyl derivative of L-cysteine
      (NAC) is a non-toxic compound of mucolytic and bacteriostatic properties that can
      interfere with the formation of biofilms. However, it can also be a source of C
      and N for undesired microorganisms, as well as a reason for some adverse human
      health effects. Consequently, novel procedures are required, that would decrease
      the take-up of NAC but not reduce its antibacterial properties. We have grafted N
      acetyl-l-cysteine onto linear poly(vinylsilsesquioxanes) and
      poly(methylvinylsiloxanes) via thiol-ene addition. Antibacterial activity of the
      obtained hybrid materials (respectively, NAC-Si-1 and NAC-Si-2) was determined
      against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus
      strains. Native NAC inhibited growth of planktonic cells for the tested bacteria
      at concentration 0.25% w/v. Inhibition with equivalent solutions of the polymer
      derivatives was less effective due to the lack of SH groups. However, the tested
      polymers proved to be quite effective in eradication of mature biofilms.
      Treatment with 1% w/v emulsions of the hybrid polymers resulted in a significant
      reduction of viable cells in biofilm matrix despite the absence of thiol
      moieties. The effect was most pronounced for mature biofilms of S. aureus
      eradicated with NAC-Si-2.

PMID- 30223246
TI  - Fluorescence detection of intracellular pH changes in the mitochondria-associated
      process of mitophagy using a hemicyanine-based fluorescent probe.
AB  - Intracellular pH behaves as a vital parameter in the physiological and
      pathological processes. Novel small molecule probes for precise and dynamic
      monitoring of pH fluctuations in cellular physiological processes are still
      highly required. Herein, we present a hemicyanine-based probe (HcPH) detection of
      the pH changes during the intracellular process of mitochondria-associated
      autophagy. HcP-H exhibits highly reversible and ratiometric fluorescence
      detection of pH variation due to the deprotonation/protonation process, showing
      orange fluorescence (lambdaem = 557 nm) in basic media (pH 8.0) and green
      fluorescence (lambdaem = 530 nm) in acidic media (pH 6.2), respectively.
      Organelle localization experiment in HeLa cells demonstrates that this probe
      could selectively accumulate in mitochondria, showing almost overlap with that of
      Mito-Tracker Green FM. More importantly, Fluorescence imaging of HcP-H in HeLa
      cells subjected to the nutrient deprivation has demonstrated that this probe
      could monitor the intracellular pH changes in the mitochondria-associated process
      of mitophagy. It is clearly confirmed that HcP-H would serve as a promising
      fluorescent probe for tracing mitophagy in living cells.

PMID- 30223247
TI  - Conformational study of the electronic interactions and nitric oxide release
      potential of new S-nitrosothiols esters derivatives of ibuprofen, naproxen and
      phenyl acids substituted (SNO-ESTERS): Synthesis, infrared spectroscopy analysis
      and theoretical calculations.
AB  - The conformational study on the new S-nitrosothiols esters (SNO-ESTERS): para
      substituted (X = H, OMe, Cl and NO2) S-nitrosothiol derivatives 2-methyl-2
      (sulfanyl)propyl phenylacetates (R1), 2-(4-isobutylphenyl)propanoate (ibuprofen,
      R2), and 2-(4-isobutylphenyl)propanoate of 2-methyl-2-(nitrososulfanyl)propyl
      (naproxen, R3) was performed using infrared spectroscopy (IR) in solvents with
      increasing polarity (CCl4, CH3Cl, and CH3CN), and theoretical calculations, to
      determine the preferential conformer and the potential of these compounds to
      release nitric oxide (NO). S-Nitrosothiols were synthesized by esterification
      reactions, using chlorides of the corresponding carboxylic acids, with good
      yields (~60%). IR results showed that these compounds presented only one
      conformation, and the experimental data were supported by the theoretical results
      obtained by density functional theory (DFT) calculations using the 6311+G (2df,
      2p) basis set. The calculations revealed that all S-nitrosothiols presented one
      preferential anticlinal (ac) geometric conformation, which agrees with the data
      obtained experimentally in CCl4. These conformers are stabilized by
      intramolecular hydrogen bonds. Examination of the geometry with regard to the
      RSNO group revealed that these compounds are preferentially in the trans (anti)
      conformation. The calculation of the orbital interactions using the Natural Bond
      Orbital (NBO) method showed that the nO(NO) -> sigma(SN)* hyper-conjugative
      interaction increases the SN bond length. The strong nS -> pi(NO)* interaction
      and electronic delocalization induces a partial pi character to the SN bond. The
      weak sigmaSN bond indicates strong delocalization of the electron pair in O (NO)
      by the nO(NO) -> sigma(SN)* interaction, thereby increasing the capacity of NO
      release from SNO-ESTERS.

PMID- 30223248
TI  - Detection and identification of medically important alkaloids using the surface
      enhanced Raman scattering spectroscopy.
AB  - Currently, trace detection of drugs, medicinal products, psychoactive substances,
      poisons and other natural or synthetic compounds in the human body has become one
      of the most important areas of interest in medicine, toxicology and forensic
      research. Due to the rapid development of nanotechnology, applications in
      forensic and biological sciences, food industry and art preservation there is an
      increasing interest in surface-enhanced Raman scattering (SERS) spectroscopy as a
      technique capable of low detection limits in the analysis of small amounts of
      studied analytes. In this study, different excitation wavelengths (785 nm and
      1064 nm) were used to find the appropriate experimental conditions for the
      detection and identification of medically significant alkaloids - atropine and
      pergolide - by means of surface-enhanced Raman scattering spectroscopy. SERS
      spectra of selected alkaloids were measured in the concentration range 10-3-10-9
      mol?L-1 using large-scaled platinum substrates coated with electrochemically
      prepared gold or silver SERS-active layers. Identification was based on the
      assignment of surface-enhanced characteristic vibrational bands using theoretical
      (DFT) calculations and comparing them with normal (non-enhanced) Raman spectra of
      pure compounds. All sets of spectral data were subjected to multivariate
      statistical approach (partial least squares regression) aiming at prediction of
      alkaloids concentration in developed models and its comparison with experimental
      results.

PMID- 30223249
TI  - The design of hydrogen sulfide fluorescence probe based on dual nucleophilic
      reaction and its application for bioimaging.
AB  - Hydrogen sulfide (H2S) can undergo dual nucleophilic reaction, which is a wise
      and effective way to distinguish biothiols and H2S. A novel H2S fluorescence
      probe, 4-{2-[4-(2-disulfide pyridyl-benzoyloxy)-phenyl]-vinyl}-1-methyl
      pyridinium[e]iodide (DSPBP), with two nucleophilic reaction sites has been
      developed. The spectra results showed that DSPBP could detect H2S in ratiometric
      and colorimetric signals and has excellent selectivity and sensitivity. The
      fluorescence ratiometric signals (F520/F450) displayed a prominent increase from
      0.74 to 7.08, the fluorescence color turned to yellow form blue simultaneously.
      The linear range was 2-14 MUM and its detection limit was 25.7 nM. Moreover, the
      biocompatibility of DSPBP was fine and its toxicity was very low. It has been
      successfully used for imaging H2S in cells.

PMID- 30223251
TI  - Enzyme targets for drug design of new anti-virulence therapeutics.
AB  - Society has benefitted greatly from the use of antibiotics. Unfortunately, the
      misuse of these valuable molecules has resulted in increased levels of antibiotic
      resistance, a major global and public health issue. This resistance and the
      reliance on a small number of biological targets for the development of
      antibiotics emphasizes the need for new targets. A critical aspect guiding the
      development of new antimicrobials through a rational structure-guided approach is
      to understand the molecular structures of specific biological targets of
      interest. Here we give an overview of the structures of bacterial virulence
      enzyme targets involved in protein folding, peptidoglycan biosynthesis and cell
      wall modification. These include enzymes of the thiol-disulphide oxidoreductase
      pathway (DSB enzymes), peptidyl-proly cis/trans isomerases (Mips), enzymes from
      the Mur pathway and enzymes involved in lipopolysaccharide modification (EptA and
      ArnT). We also present progress towards inhibitor design of these targets for the
      development of novel anti-virulence therapeutic agents.

PMID- 30223250
TI  - Recently approved therapies in acute myeloid leukemia: A complex treatment
      landscape.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease. Until recently,
      treatment for patients with AML was limited to induction chemotherapy with
      cytarabine and anthracycline or hypomethylating agents, and, in some instances,
      allogeneic hematopoietic stem cell transplant. With the recent approval of new
      therapies-i.e., CPX-351, enasidenib, ivosidenib, gemtuzumab ozogamicin, and
      midostaurin-a new era in AML treatment has emerged. Comprehensive diagnostic
      testing, such as cytogenetic and molecular testing, is necessary for establishing
      patient eligibility for these new agents and should be performed in a timely
      manner. However, choosing a therapy for patients who are eligible for multiple
      treatments may be a complex process, particularly for patients with newly
      diagnosed AML. This review discusses data, including associated safety profiles
      that supported these recent approvals, and provides insights to help clinicians
      navigate new therapy options for this devastating disease. Given the
      heterogeneity of AML, the treatment landscape will likely continue to grow and
      evolve as additional agents (and their combinations) are approved for the
      treatment of subpopulations of patients with AML. Physicians will need to remain
      abreast of the ever-changing treatment landscape.

PMID- 30223252
TI  - Comparative performance of human papillomavirus messenger RNA versus DNA
      screening tests at baseline and 48 months in the HPV FOCAL trial.
AB  - BACKGROUND: HPV FOCAL is a randomized trial comparing high-risk HPV [Hybrid
      Capture 2 (HC2)] vs. liquid-based cytology (LBC) for primary cervical screening.
      OBJECTIVE: The present study objective was to compare Aptima HPV (AHPV) and HC2
      assay performance at the intervention arm baseline and 48 mo. screens in relation
      to the rates of cervical intraepithelial neoplasia (CIN) grade 2 or worse
      (CIN2+). STUDY DESIGN: Women enrolled after December 2010 (n = 3475) were
      screened at baseline with both AHPV and HC2 (AHPV was blinded). Women with CIN2+
      exited the trial; HC2 negative (-) women and those HC2 positive (+) with <CIN2
      returned for 48 mo. screening with AHPV, HC2, and LBC. RESULTS: At baseline, 7.2%
      were AHPV + vs. 8.4% for HC2 (p = 0.06). Round 1 AHPV CIN2+ sensitivity (relative
      to HC2) was 96.0% (95%CI: 86.5-99.0; p = 0.15) and 100% (95%CI: 82.4-100) for
      CIN3+. AHPV and HC2 specificities (<CIN2) were 94.1% vs. 93.0% respectively (p =
      0.05). At 48 mo., 4.8% and 5.2% were AHPV+ and HC2+ respectively (p = 0.41), and
      both tests had the same CIN2+ and CIN3+ sensitivities (87.5% and 85.0%
      respectively). AHPV specificity (95.8%) was higher, but not significantly, than
      HC2 (95.3%; p = 0.38). Of 3226 baseline AHPV- women, 12/2,858 (0.4%) had CIN2+
      vs. 13/2821 (0.5%) for the 3184 baseline HC2- women. CONCLUSIONS: There was no
      significant difference in CIN2+ detection for AHPV vs. HC2 at baseline or at 48
      mo. Baseline AHPV- and HC2- women had similar CIN2+ rates at 48 mo.,
      demonstrating the safety of a four year screening interval for AHPV- women.

PMID- 30223253
TI  - Validation of EUROArray HPV test using the VALGENT framework.
AB  - BACKGROUND: Robust clinical and analytical validation of human papillomavirus
      (HPV) tests is a pre-requisite for their use in cervical cancer screening given
      the transience of most high-risk HPV infections. OBJECTIVES: To evaluate the
      EUROArray HPV test (PCR-based full HPV genotyping test) using the international
      validation of the VALGENT framework, which offers an opportunity to determine
      analytical and clinical performance according to internationally accepted
      performance metrics. STUDY DESIGN: A total of 1300 consecutive and 300 abnormal
      cervical samples derived from the Slovenian screening programme were tested with
      the EUROArray HPV test. Clinical performance for the detection of cervical
      intraepithelial neoplasia grade 2 and above (CIN2+) was performed and compared to
      a standard comparator test (Hybrid Capture 2). Intra- and inter-laboratory
      reproducibility of the assay was performed in a subset of 500 samples. RESULTS:
      The relative clinical sensitivity and specificity of EUROArray HPV vs HC2 was
      0.93 (95% Confidence Interval (CI), 0.88-0.99; P non-inferiority(ni) = 0.1413)
      and 1.01 (95% CI, 0.99-1.02; Pni = 0.0001), respectively. Application of an a
      posteriori cut-off for HPV16 led to relative values of 0.98 (95% CI, 0.92-1.03;
      Pni = 0.0076) and 1.00 (95% CI, 0.97-1.03; Pni = 0.007), respectively. The assay
      showed excellent intra- and inter-laboratory reproducibility (concordance >= 94%,
      Kappas >=0.85). CONCLUSION: At the predefined cut-off, EUROArray HPV was less
      sensitive than HC2 for the detection of CIN2+. However, when an optimised cut-off
      was applied, EUROArray HPV fulfilled international criteria for its use in
      cervical cancer screening.

PMID- 30223254
TI  - Evaluating the relationship between gait and clinical measures of plantar flexor
      function.
AB  - Individuals with plantar flexor weakness often require rehabilitation and/or
      orthoses, which should be personalized based on level of weakness. While plantar
      flexor weakness can be measured via peak plantar flexion moment during gait
      (MGAIT), motion analysis systems are often not clinically available. Clinical
      measures, such as the single-leg heel rise (SLHR) test and isometric muscle test,
      may provide surrogate measures of plantar flexor function during gait. However,
      it is currently unknown if a relationship(s) exists between such measures. This
      study evaluated the relationship between gait and clinical measures of plantar
      flexor function for typical individuals. Twenty-four participants underwent an
      instrumented gait analysis, from which MGAIT was calculated. Next, participants
      performed an isometric plantar flexor test, from which the maximum plantar
      flexion moment (MISO) was calculated. Finally, participants performed a SLHR
      test, from which maximum plantar flexion moment (MSLHR) and total work
      (Wtot_SLHR) were calculated. Via Pearson correlations, MSLHR was most strongly
      correlated to MGAIT (r = 0.56; p = 0.005). Wtot_SLHR was significantly correlated
      to MGAIT (r = 0.47; p = 0.019). MISO was not significantly correlated to MGAIT (r
      = 0.19; p = 0.363). MSLHR and/or Wtot_SLHR may provide clinically-feasible
      surrogate measures of plantar flexor function during gait.

PMID- 30223255
TI  - Congenital Pouch Colon: Role of Genetics or Environmental Influence?
AB  - BACKGROUND: Congenital pouch colon (CPC), a high type of anorectal malformation,
      is a sporadic disease and several environmental factors are known to be involved
      in its pathology. To the best of our knowledge, no familial incidence of CPC has
      been reported anywhere in the literature so far. AIM: In the present study, which
      is first of its kind, we have reported the familial incidences of CPC and also
      tried to elucidate the role of genetics in this pathology. METHODS: We have
      reported 1 familial pedigree of CPC and 2 incidences of dizygotic twins (DZ), out
      of them one is affected and another one is normal. Highly comprehensive
      microarray CytoScan HD from Affymetrix was employed to understand the defects
      underlying submicroscopic genomic imbalance like segment duplication and deletion
      of the twin patients vis-a-vis their parents and unaffected siblings in these DZ
      twins. RESULTS: A total of 21 copy number variations (CNVs) were reported in the
      patient samples that did not overlap with the CNVs in normal parents and healthy
      sibling, including 5 loss, 3 LOH and 13 gain with size varied from 95 bp to 77
      kbp. Genetic analysis revealed involvement of 12 potential genetic loci on Chr 1,
      2, 3, 4, 6, 11, and 16. CONCLUSION: Genetic study found that CPC could be a
      developmental disorder. These findings are important for further elucidating
      genetic causes of CPC pathogenesis.

PMID- 30223256
TI  - Peritoneal Dialysis as an Option for Unplanned Dialysis Initiation in Patients
      with End-Stage Renal Disease and Diabetes Mellitus.
AB  - AIMS: This study aimed to compare the short-term complications and long-term
      prognosis between urgent-start peritoneal dialysis (PD) and hemodialysis (HD),
      and explore the safety and feasibility of PD in end-stage renal disease (ESRD)
      patients with diabetes. METHODS: This retrospective study enrolled ESRD patients
      with diabetes who required urgent-start dialysis at a single center from January
      2011 to December 2014. Short-term (30-day) dialysis-related complications and
      patient survival trends were compared between patients receiving PD and HD.
      RESULTS: Eighty patients were included in the study, including 50 (62.5%) who
      underwent PD. The incidence of dialysis-related complications and complications
      requiring reinsertion during the first 30 days was significantly lower in PD
      patients. Logistic regression identified urgent-start HD as an independent risk
      factor for dialysis-related complications compared with urgent-start PD. The
      patient survival rate was higher in the PD compared to that in the HD group.
      CONCLUSIONS: PD may be acceptable, safe, and feasible for urgent-start dialysis
      in ESRD patients with diabetes.

PMID- 30223258
TI  - Association of the Polymorphisms and Plasma Level of CHI3L1 with Alzheimer's
      Disease in the Chinese Han Population: A Case-Control Study.
AB  - OBJECTIVE: To investigate whether the polymorphisms and plasma level of chitinase
      3-like protein 1 (CHI3L1) are associated with Alzheimer's disease (AD) in the
      Chinese Han population. METHODS: A total of 166 patients who were initially
      diagnosed with AD were enrolled as the case group, and 184 healthy subjects were
      recruited as the healthy controls. TaqMan(r) SNP genotyping assays were applied
      for the genotyping of rs4950928, rs10399931 and rs6691378. The plasma level of
      CHI3L1 was determined by enzyme-linked immunosorbent assay. RESULTS: The CG+GG
      genotype of rs4950928 C>G is a protective factor for AD and could effectively
      reduce the severity of AD. Patients with the CT+TT genotype of rs10399931 C>T had
      a significantly increased risk of AD, and it apparently aggravated the severity
      of AD. Moreover, the plasma CHI3L1 level in AD patients was significantly higher
      than that in healthy controls, which was increased with the severity of AD. A
      Kaplan-Meier survival curve showed that significant differences in 5-year
      survival rates were found in AD patients in different genotypes of CHI3L1
      rs4950928 C>G and rs10399931 C>T. The AD patients and healthy controls who
      carried the CG+GG genotype of rs4950928 C>G had lower plasma CHI3L1 levels than
      CC genotype carriers. However, the CT+TT genotype of rs10399931 in the AD
      patients had an elevated plasma level of CHI3L1 as compared with the CC genotype.
      Binary logistic regression analysis showed that the plasma level of CHI3L1, the
      CC genotype of rs4950928 C>G and the CT+TT genotype of rs10399931 C>T were risk
      factors for AD. CONCLUSION: Polymorphisms of the CHI3L1 gene (rs4950928 C>G and
      rs10399931 C>T) are associated with the risk and prognosis of AD and can affect
      the expression of CHI3L1 in plasma.

PMID- 30223257
TI  - In Silico Identification and in Vitro Analysis of B and T-Cell Epitopes of the
      Black Turtle Bean (Phaseolus Vulgaris L.) Lectin.
AB  - BACKGROUND/AIMS: The incidence of lectin allergic disease is increasing in recent
      decades, and definitive treatment is still lacking. Identification of B and T
      cell epitopes of allergen will be useful in understanding the allergen antibody
      responses as well as aiding in the development of new diagnostics and therapy
      regimens for lectin poisoning. In the current study, we mainly addressed these
      questions. METHODS: Three-dimensional structure of the lectin from black turtle
      bean (Phaseolus vulgaris L.) was modeled using the structural template of
      Phytohemagglutinin from P. vulgaris (PHA-E, PDB ID: 3wcs.1.A) with high identity.
      The B and T-cell epitopes were screened and identified by immunoinformatics and
      subsequently validated by ELISA, lymphocyte proliferation and cytokine profile
      analyses. RESULTS: Seven potential B-cell epitopes (B1 to B7) were identified by
      sequence and structure based methods, while three T-cell epitopes (T1 to T3) were
      identified by the predictions of binding score and inhibitory concentration. The
      epitope peptides were synthesized. Significant IgE binding capability was found
      in B-cell epitopes (B2, B5, B6 and B7) and T2 (a cryptic B-cell epitope). T1 and
      T2 induced significant lymphoproliferation, and the release of IL-4 and IL-5
      cytokine confirmed the validity of T-cell epitope prediction. Abundant
      hydrophobic amino acids were found in B-cell epitope and T-cell epitope regions
      by amino acid analysis. Positively charged amino acids, such as His residue,
      might be more favored for B-cell epitope. CONCLUSION: The present approach can be
      applied for the identification of epitopes in novel allergen proteins and thus
      for designing diagnostics and therapies in lectin allergy.

PMID- 30223260
TI  - Retraction Statement.

PMID- 30223259
TI  - Metastatic Prostate Carcinoma from Imperial Rome (1st to 2nd Centuries AD).
AB  - OBJECTIVE: This study describes and discusses a rare case of metastatic carcinoma
      that affected the skeleton of an adult male recovered in the necropolis of Casal
      Bertone in Rome (Italy). The necropolis, which dates back to the Imperial Age
      (1st to 2nd century AD), is located near some residential structures and a large
      place identified as a fullery (fullonica). METHODS: Anthropological and
      paleopathological studies of the skeletal remains were performed via careful
      macroscopic, microscopic, radiological (X-ray and CT scan), and histological
      investigation. RESULTS: The skeleton displayed mixed osteoclastic and
      osteoblastic lesions that mainly involved the axial bones, in particular the
      sternum, the ribs, the spine, and the scapular and pelvic girdles. The anatomical
      distribution and the destructive and proliferative nature of the lesions
      suggested diffuse metastases arising from a soft-tissue primary cancer. The age
      and sex of the individual, as well as radiographic and histological pictures,
      allowed diagnosis of an advanced prostate cancer with extensively diffused bone
      metastases. CONCLUSION: At present, this is the only case of prostate cancer from
      the Imperial Age recovered in Rome.

PMID- 30223261
TI  - Ethical, Legal, and Regulatory Issues for the Implementation of Omics-Based Risk
      Prediction of Women's Cancer: Points to Consider.
AB  - BACKGROUND AND OBJECTIVE: Advances in omics open new opportunities for cancer
      risk prediction and risk-based screening interventions. However, implementation
      of risk prediction in clinical practice may impact the ethical, legal, and
      regulatory aspects of current cancer screening programs. In order to support
      decision-making, we analyzed the ethical, legal, and regulatory issues and
      developed a set of Points to Consider to support management of these issues.
      METHODS: We analyzed the legal and policy frameworks applicable to breast and
      cervical cancer screening programs in 7 European countries. We identified the
      most relevant issues to be considered, and we developed considerations for their
      management, based on the literature, the legal and policy frameworks, and our
      experience with similar issues. RESULTS: The considerations focus on five topics:
      (A) health services planning, (B) information and invitation, (C) consent and
      data/sample collection, (D) risk calculation and communication of results, and
      (E) storage of data and residual samples. CONCLUSION: Current frameworks might
      not be adequate to implement a risk prediction approach using omics factors due
      to the different characteristics of such approaches.

PMID- 30223262
TI  - Chronic Maternal Hyperoxygenation and Effect on Cerebral and Placental
      Vasoregulation and Neurodevelopment in Fetuses with Left Heart Hypoplasia.
AB  - INTRODUCTION: In a pilot study of chronic maternal hyperoxygenation (CMH) in left
      heart hypoplasia (LHH), we sought to determine effect estimates of CMH on head
      size, vascular resistance indices, and neurodevelopment compared to controls.
      MATERIAL AND METHODS: Nine gravidae meeting the inclusion criteria (fetal LHH,
      >=25.9 weeks' gestation, and >=10% increase in percent aortic flow after acute
      hyperoxygenation) were prospectively enrolled. Controls were 9 contemporary
      gravidae with fetal LHH without CMH. Brain growth and Doppler-derived estimates
      of fetal cerebrovascular and placental resistance were blindly evaluated and
      compared using longitudinal regression. Postnatal anthropomorphic and
      neurodevelopmental assessments were compared. RESULTS: There was no difference in
      baseline fetal measures between groups. There was significantly slower biparietal
      diameter (BPD) growth in the CMH group (z-score change -0.03 +/- 0.02 vs. +0.09
      +/- 0.05 units/week, p = 0.02). At 6 months postnatal age, the mean head
      circumference z-score in the CMH group was smaller than that of controls (-0.20
      +/- 0.58 vs. +0.85 +/- 1.11, p = 0.048). There were no differences in
      neurodevelopmental testing at 6 and 12 months. DISCUSSION: In this pilot study,
      relatively diminished fetal BPD growth and smaller infant head circumference z
      scores at 6 months were noted with in utero CMH exposure.

PMID- 30223263
TI  - The Role of Nutrition and the Gut-Brain Axis in Psychiatry: A Review of the
      Literature.
AB  - INTRODUCTION: Individuals suffering from psychiatric disorders experience high
      levels of illness burden and a significantly reduced quality of life. Despite
      targeted psychopharmacological strategies and complementary psychotherapeutic
      procedures only moderate effects are obtained, and the risk of relapse is high in
      many patients. Worldwide, psychiatric diseases such as depression are
      continuously increasing, challenging the personal life of the affected as well as
      their families, but also whole societies by increasing disability, early
      retirement and hospitalization. According to current scientific knowledge
      psychiatric disorders are caused by a multifactorial pathogenesis, including
      genetics, inflammation and neurotransmitter imbalance; furthermore, also
      lifestyle-associated factors gain rising importance. In line with this, there is
      growing evidence that the gut microbiota and nutrition have an impact on the
      onset and course of psychiatric disorders. AIM: This narrative review highlights
      the important role of nutrition in psychiatric care and underlines the
      significance of nutritional advice in the multifactorial, biopsychosocial
      treatment of patients. It focuses on current dietary interventions such as the
      Mediterranean diet, dietary supplements and modifications of the gut microbiota
      with pre-, pro- and postbiotics. RESULTS: Recent studies support the connection
      between the quality of diet, gut microbiota and mental health through regulation
      of metabolic functions, anti-inflammatory and antiapoptotic properties and the
      support of neurogenesis. Dietary coaching to improve mental health seems to be an
      additional, cost-effective, practical, nonpharmacological intervention for
      individuals with psychiatric disorders. CONCLUSION: The use of nutritional
      interventions in psychiatry equips therapists with a promising tool for both the
      prevention and treatment of psychiatric disorders. Besides pharmacological
      therapy, psychotherapy and physical activity, nutritional interventions are an
      important pillar in the multifactorial, biopsychosocial treatment of psychiatric
      disease and could be used as a potential therapeutic target.

PMID- 30223264
TI  - miR-184 Inhibits Tumor Invasion, Migration and Metastasis in Nasopharyngeal
      Carcinoma by Targeting Notch2.
AB  - BACKGROUND/AIMS: A recent study found that dysregulated microRNA-184 (miR-184) is
      involved in the proliferation and survival of nasopharyngeal carcinoma (NPC).
      This study aimed to evaluate the detailed mechanisms of invasion, migration and
      metastasis of NPC cells. METHODS: Quantitative reverse-transcription PCR (qRT
      PCR) and Western blot were used to confirm the expression levels of miR-184 and
      Notch2. NPC cell invasion and migration were subsequently examined using in vitro
      cell invasion and wound-healing assays, respectively. MicroRNA (miRNA) target
      gene prediction databases and dual-luciferase reporter assay were adopted to
      validate the target genes of miR-184. RESULTS: MiR-184 was downregulated in the
      NPC cell lines. The miR-184 inhibitor increased the number of invading NPC cells,
      whereas miR-184 mimics inhibited the invasive ability of such cells. The protein
      level of E-cadherin decreased, whereas those of N-cadherin and vimentin increased
      in the anti-miR-184 group. This result showed that miR-184 inhibited NPC cell
      invasion and metastasis by regulating EMT progression. MiRNA target gene
      prediction databases indicated the potential of Notch2 as a direct target gene of
      miR-184. Such a notion was then validated by results of dual-luciferase reporter
      assay. Notably, shRNANotch2 restrained the EMT and partially abrogated the
      inhibitory effects of miR-184 on EMT progression in NPC cells. CONCLUSION: MiR
      184 functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the
      invasion, migration and metastasis of NPC.

PMID- 30223265
TI  - The in Vitro Effect of Polyvinylpyrrolidone and Citrate Coated Silver
      Nanoparticles on Erythrocytic Oxidative Damage and Eryptosis.
AB  - BACKGROUND/AIMS: Silver nanoparticles (AgNPs) are increasingly used as
      antimicrobial agents and drug carriers in various biomedical fields. AgNPs can
      encounter erythrocytes either directly following intravenous injection, or
      indirectly via translocation from the site of administration. However,
      information regarding the pathophysiological effects and possible mechanism of
      action of AgNPs on the erythrocytes are still inadequately studied. Thus, the aim
      of our study was to investigate the mechanism underlying the effect of coating
      and concentration of AgNPs on mouse erythrocytes in vitro. METHODS: We studied
      the interaction of polyvinylpyrrolidone (PVP) and citrate (CT) coated AgNPs (10
      nm) at various concentrations (2.5, 10, 40 ug/ml) with mouse erythrocytes in
      vitro using various techniques including transmission electron microscopy (TEM),
      hemolysis, and colorimetric measurement of markers of oxidative stress comprising
      malondialdehyde (MDA), reduced glutathione (GSH), and catalase (CAT).
      Intracellular calcium (Ca2+) was determined using Fura 2AM fluorescence. Annexin
      V was quantified using ELISA and the caspase 3 was determined both
      flurometrically and by western blot technique. RESULTS: Following incubation of
      the erythrocytes with AgNPs, both PVP- and CT- AgNPs induced significant and dose
      - dependent increase in hemolysis. TEM revealed that both PVP- and CT- AgNPs were
      taken up by erythrocytes. The erythrocyte susceptibility to lipid peroxidation
      measured by MDA was significantly increased in both PVP-and CT- AgNPs. The
      concentration of GSH and CAT activity were significantly decreased by both types
      of AgNPs. Additionally, PVP- and CT- AgNPs significantly increased intracellular
      Ca2+ in a dose -dependent manner. Likewise, the concentration of the cellular
      protein annexin V was significantly and dose - dependently enhanced by both types
      of AgNPs. Furthermore, PVP- and CT- AgNPs induced significant increase in calpain
      activity in incubated erythrocytes. CONCLUSION: We conclude that both PVP- and CT
      AgNPs causes hemolysis, and are taken up by erythrocytes. Moreover, we
      demonstrated that AgNPs induces oxidative stress and eryptosis. These findings
      provide evidence for the potential pathophysiological effect of PVP-and CT- AgNPs
      on erythrocyte physiology.

PMID- 30223266
TI  - Immunohistochemical and Molecular Analyses Focusing on Mesenchymal Cells in
      Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis.
AB  - OBJECTIVE: This study was designed to evaluate the prevalence of CTNNB1 (beta
      catenin) mutations in cases of papillary thyroid carcinoma with desmoid-type
      fibromatosis (PTC-DTF) expressing aberrant nuclear and cytoplasmic
      immunoreactivity for beta-catenin. METHODS: Eight cases of PTC-DTF were available
      for this study. Immunohistochemistry for beta-catenin and BRAFV600E was
      performed. CTNNB1 and BRAFV600E mutations were also evaluated by direct
      sequencing. RESULTS: For beta-catenin, although we could demonstrate aberrant
      nuclear and cytoplasmic immunoreactivity in DTF components in all cases,
      suggesting activated Wnt signaling, direct sequencing revealed a missense
      mutation, c.121A>G (p.T41A), in exon 3 in only one case, and no mutations in
      exons 3, 4, and 5 in the other cases. In the BRAFV600E analyses,
      immunohistochemistry revealed positive staining in the carcinoma cells but not
      DTF components of all cases. These findings were subsequently validated by direct
      sequencing. CONCLUSION: This study suggests the significance of the BRAFV600E
      mutation and activation of Wnt signaling pathway in the carcinoma cells and DTF
      components, respectively. We believe that the CTNNB1 mutations are not the major
      factor behind beta-catenin translocation indicating Wnt pathway activation.
      Further study is required to evaluate whether molecular abnormalities other than
      the CTNNB1 mutation cause activation of Wnt signaling in DTF components of PTC
      DTF.

PMID- 30223268
TI  - Airway-Centered Pleuroparenchymal Fibroelastosis Associated with Non-Necrotizing
      Granulomas: A Rare New Entity.
AB  - Pleuroparenchymal fibroelastosis is a rare form of upper-lobe-dominant
      progressive pulmonary fibrosis characterized histologically by visceral pleural
      thickening with collagenous fibrosis, subpleural elastosis, and intra-alveolar
      collagenous fibrosis. It was first described 25 years ago by Amitani et al. This
      report firstly describes a new variant or rare phenotype of PPFE with airway
      involvement, minimal pleuroparenchymal connections, and non-necrotizing
      granulomas.

PMID- 30223267
TI  - A Bayesian Network Meta-Analysis Comparing the Efficacies of Eleven Novel
      Therapies with the Common Salvage Regimen for Relapsed or Refractory Acute
      Myeloid Leukemia.
AB  - BACKGROUND/AIMS: Acute myeloid leukemia (AML) is a relapsed and refractory
      hematological malignancy with a lower morbidity but higher mortality. In addition
      to hematopoietic stem cell transplantation, chemotherapy is used as the front
      line treatment. However, the diversity of available agents and the inconsistency
      of outcomes of relevant trials render treatment decision-making tough. Network
      meta-analysis (NMA) is an efficient statistical framework that makes a
      comprehensive comparison and provides a valuable clinical reference. METHODS: All
      the potential trials were retrieved from the medical database and screened
      according to the inclusion and exclusion criteria. The main characteristics of
      each trial as well as the primary outcomes, including complete remission (CR),
      overall response rate (ORR), overall survival (OS), and event-free survival
      (EFS), were extracted. In addition, the network graph was plotted to illustrate
      the connections among the trials involved. Comparison results in the network were
      exhibited in a forest plot. Furthermore, the surface under the cumulative ranking
      curve (SUCRA) was introduced to rank the treatments for each endpoint. RESULTS: A
      total of 11 trials were selected from 1,625 identifications. No significant
      difference in the common treatment was observed for the endpoints CR and ORR. In
      terms of OS, CPX-351 (HR: 0.77, 95% CrI: 0.63, 0.94) and HiDAC plus MK-8776 (HR:
      0.80, 95% CrI: 0.68, 0.93) showed a superiority over the common salvage regimen
      in the short term, while HiDAC plus MK-8776 (HR: 0.80, 95% CrI: 0.70, 0.93) and
      Ara-C plus vosaroxin (HR: 0.86, 95% CrI: 0.74, 0.99) outperformed the common
      salvage regimen for the 3-year OS. In addition, clofarabine plus Ara-C (HR: 0.61,
      95% CrI: 0.53, 0.69) and CPX-351 (HR: 0.71, 95% CrI: 0.60, 0.83) were confirmed
      to be efficacious in enhancing the rate of EFS. CONCLUSION: Referring to the
      network outcome and SUCRA value, clofarabine plus Ara-C (CR: 79.05%, ORR: 80.02%)
      and Ara-C plus vosaroxin (CR: 75.42%, ORR: 73.43%) were potentially the top two
      choices for both CR and ORR. CPX-351 (1-year OS: 91.36%), HiDAC plus MK-8776 (3
      year OS: 94.23%) and clofarabine plus Ara-C (1-year EFS: 97.34%) yielded the
      highest probabilities to be the optimal choices for 1-year OS, 3-year OS and 1
      year EFS, respectively.

PMID- 30223269
TI  - Impact of KDIGO-Defined Acute Kidney Injury on Mortality after Percutaneous
      Coronary Intervention for Acute Myocardial Infarction.
AB  - BACKGROUND: There are limited data regarding the incidence and long-term impact
      of acute kidney injury (AKI) according to the KDIGO guidelines on the outcome in
      patients with myocardial infarction (MI) treated with percutaneous coronary
      intervention (PCI). The aim of the study was to evaluate the prevalence of AKI,
      as classified by the KDIGO criteria, and its association with long-term
      mortality. METHODS: Data from 5,859 MI patients undergoing PCI at our institution
      were analyzed. We compared the group without and with AKI according to the KDIGO
      criteria in relation to long-term mortality. RESULTS: AKI was documented in 499
      (8.5%) patients. AKI stage 1 occurred in 6.2% of patients, AKI stage 2 in 0.9% of
      patients, and AKI stage 3 in 1.5% of patients. Patients with AKI had a higher
      long-term mortality (57.3 vs. 20.6%; p < 0.0001). The mortality was 50.3% in AKI
      stage 1, 56.9% in AKI stage 2, and 87.2% in AKI stage 3. The hazard ratios for
      all-cause mortality for AKI stages 1-3 were 1.77, 1.85, and 6.30 compared to
      patients with no AKI. Cardiogenic shock, bleeding, heart failure, age, renal
      dysfunction, diabetes, hyperlipidemia, ST-elevation MI, contrast
      volume/glomerular filtration ratio, P2Y12 receptor antagonists, and radial access
      were associated with the development of AKI. CONCLUSION: A slight increase in
      serum creatinine was associated with a progressive increase in long-term
      mortality in patients with AKI according to the KDIGO definition.

PMID- 30223270
TI  - Differential Expression of Cancer-Associated Fibroblast-Related Proteins in
      Ductal Carcinoma in situ According to Molecular Subtype and Stromal Histology.
AB  - OBJECTIVE: The purpose of this study is to investigate the expression of cancer
      associated fibroblast (CAF)-related proteins and their implication in ductal
      carcinoma in situ (DCIS). METHODS: We constructed a tissue microarray of 223
      cases of DCIS and examined immunohistochemical staining for the 7 CAF-related
      proteins. We classified DCIS into luminal type, human epidermal growth factor
      receptor-2 (HER-2) type, and triple negative breast cancer (TNBC) according to
      the immunohistochemical results for estrogen receptor, progesterone receptor, and
      HER-2. We also classified DCIS into desmoplastic, normal-like, and inflammatory
      type according to stromal histology. RESULTS: There were significant differences
      in the expression of S100A4, podoplanin, prolyl 4-hydroxylase subunit alpha 3,
      NG2, and PDGFRalpha in stromal cells of DCIS when classified according to
      molecular subtype. The expression rate of all CAF-related proteins in stromal
      cells was higher in the HER-2 type and TNBC than in the luminal type (p < 0.001).
      When classified according to stromal subtype, there were significant differences
      in the expression of all CAF-related proteins in stromal cells, with the
      inflammatory stromal type showing higher expression of CAF-related proteins than
      other stromal types. CONCLUSION: The expression of CAF-related proteins in
      stromal cells of DCIS varies according to molecular subtype and stromal type.

PMID- 30223271
TI  - The Importance of Adherence in the Treatment of Secondary Hyperparathyroidism.
AB  - Secondary hyperparathyroidism (SHPT) is a frequent condition in the presence of
      chronic kidney disease (CKD). In CKD patients, SHPT is reported to increase both
      morbidity and mortality, especially cardiovascular. The difficulty in the
      treatment of SHPT in clinical practice is frequently encountered from a not
      always adequate conduct of the clinicians and a common non-compliance to the
      therapy of CKD patients. In this review, the greatest difficulties from
      clinicians and CKD-patients' point of view in the treatment of SHPT will be
      addressed, with particular attention to those related to dialysis features,
      nutritional habits, and medical therapy.

PMID- 30223272
TI  - Sterile Inflammatory Role of High Mobility Group Box 1 Protein: Biological
      Functions and Involvement in Disease.
AB  - High mobility group box 1 protein (HMGB1), a sterile inflammatory molecule and
      damage-associated molecular pattern (DAMP) released from various cells during
      stress has been implicated in inflammation. Several reports show that there is a
      direct relationship between inflammation and cardiovascular diseases (CVDs) such
      as thrombosis, hypertension, insulin resistance, preeclampsia, etc. Here, we
      intend to summarize the concept of the emerging link between HMGB1 and CVDs.
      Furthermore, we will discuss the possible therapeutic strategies that target
      HMGB1 for the treatment of different CVDs.

PMID- 30223273
TI  - Hepatorenal Syndrome or Hepatocardiorenal Syndrome: Revisiting Basic Concepts in
      View of Emerging Data.
AB  - BACKGROUND: Accumulating evidence on the pathophysiology of hepatorenal syndrome
      has challenged the conventional model of liver-kidney connection. While liver
      cirrhosis is traditionally considered the origin of a cascade of pathophysiologic
      mechanisms directly affecting other organs such as the kidney, emerging data
      point to the heart as the potential mediator of the untoward renal effects.
      SUMMARY: Herein, we briefly review the often-overlooked contribution of the heart
      to circulatory dysfunction in hepatorenal syndrome and put forward evidence
      arguing for the involvement of systemic inflammation and endothelial dysfunction
      in this setting. The temporality of cardiorenal interactions in hepatorenal
      syndrome and the observed beneficial effects of portosystemic shunting on these
      pathways lend further support to the notion that cardiac involvement plays a key
      role in the development of renal dysfunction in severe cirrhosis. Key Messages:
      The disturbances traditionally bundled within hepatorenal syndrome could
      represent a hepatic form of cardiorenal syndrome whereby the liver affects the
      kidney in part through cardiorenal pathways. This new model has practical
      implications and calls for a shift in the focus of diagnostic and therapeutic
      approaches to renal dysfunction in advanced cirrhosis.

PMID- 30223274
TI  - The Recurrence Risk of Fetomaternal Hemorrhage.
AB  - Massive fetomaternal hemorrhage (FMH) can cause devastating pregnancy outcomes.
      Perinatal prognosis may be improved by intrauterine transfusion, but the
      appropriate management for these pregnancies remains unclear. To determine the
      recurrence risk of FMH after intrauterine transfusion, we performed a systematic
      review of all case reports/series of patients with proven FMH treated with
      intrauterine transfusion and who had subsequent follow-up of at least 72 h until
      delivery. This revealed 13 cases, with 1 additional case from our institution.
      Ten patients (71.4%) had a second episode of FMH requiring a second intrauterine
      transfusion. Five patients (35.7%) required at least 3 intrauterine transfusions.
      The time interval between intrauterine transfusions was progressively reduced.
      The gestational age at the onset of signs/symptoms was 26.6 +/- 2.1 weeks, and
      gestational age at delivery was 34.2 +/- 4.2 weeks. Two cases of fetal demise
      (14.3%) and no neonatal deaths were recorded. Limited postnatal follow-up on 8
      neonates was normal. The mean neonatal hemoglobin and transfusion rates were 13.2
      +/- 5.7 g/dL and 33.3%, respectively. Close fetal monitoring, likely daily, is
      necessary to recognize FMH recurrence. Several transfusions may be necessary once
      FMH is diagnosed if pregnancy is allowed to continue > 72 h.

PMID- 30223275
TI  - Proliferation Potential-Related Protein Promotes the Esophageal Cancer Cell
      Proliferation, Migration and Suppresses Apoptosis by Mediating the Expression of
      p53 and Interleukin-17.
AB  - OBJECTIVE: This study aims to investigate the mechanism of proliferation
      potential-related protein (PP-RP) in influencing the proliferation, migration,
      and apoptosis of esophageal cancer cells. METHODS: Quantitative real-time PCR and
      western blotting were performed to analyze the expression of PP-RP gene, p53, and
      interleukin (IL)-17 in human normal tissues and tumor tissues, as well as the
      expression of p53 and IL-17 in Eca109 and TE3 cells. The esophageal cancer cell
      proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT), cell apoptosis was detected by flow cytometry,
      and cell migration was detected by transwell migration. RESULTS: PP-RP expressed
      highly in tumor tissue and Eca109 and TE3 cells, PP-RP overexpression inhibited
      the expression of p53 and promoted the expression of IL-17 in Eca109 and TE3
      cells. PP-RP overexpression increased the expression of F-actin, promoted cell
      proliferation, and migration and suppressed cell apoptosis. Cell proliferation
      ability and cell migration ability were significantly strengthened while
      apoptosis was suppressed by PP-RP + pyruvate carboxylase deoxyribonucleic acid
      (PCDNA)-p53 group and PP-RP + IL-17 siRNA group in TE3 cells. CONCLUSION: Our
      data suggest that PP-RP promotes esophageal cancer cell proliferation and
      migration, and suppresses apoptosis by mediating the expression of p53 and IL-17.

PMID- 30223277
TI  - Comparative Analysis of Biological and Functional Properties of Bone Marrow
      Mesenchymal Stromal Cells Expanded in Media with Different Platelet Lysate
      Content.
AB  - Due to their ability to induce immunological tolerance in the recipient,
      mesenchymal stromal cells (MSCs) have been utilized in the treatment of various
      hematological and immune- and inflammation-mediated diseases. The clinical
      application of MSCs implies prior in vitro expansion that usually includes the
      use of fetal bovine serum (FBS). The present study evaluated the effect of
      different platelet lysate (PL) media content on the biological properties of
      MSCs. MSCs were isolated from the bone marrow of 13 healthy individuals and
      subsequently expanded in three different culture conditions (10% PL, 5% PL, 10%
      FBS) during 4 passages. The cells cultured in different conditions had comparable
      immunophenotype, clonogenic potential, and differentiation capacity. However, MSC
      growth was significantly enhanced in the presence of PL. Cultures supplemented
      with 10% PL had a higher number of cumulative population doublings in all
      passages when compared to the 5% PL condition (p < 0.03). Such a difference was
      also observed when 10% PL and 10% FBS conditions were compared (p < 0.005). A
      statistically significant difference in population doubling time was determined
      only between the 10% PL and 10% FBS conditions (p < 0.005). Furthermore, MSCs
      cultured in 10% PL were able to cause a 66.9% reduction of mitogen-induced
      lymphocyte proliferation. Three chromosome aberrations were detected in PL
      conditions. Since two changes occurred in the same do nor, it is possible they
      were donor dependent rather than caused by the culture condition. These findings
      demonstrate that a 10% PL condition enables a higher yield of MSCs within a
      shorter time without altering MSC properties, and should be favored over the 5%
      PL condition.

PMID- 30223276
TI  - Repression of PDK1- and LncRNA HOTAIR-Mediated EZH2 Gene Expression Contributes
      to the Enhancement of Atractylenolide 1 and Erlotinib in the Inhibition of Human
      Lung Cancer Cells.
AB  - BACKGROUND/AIMS: We previously showed that the major bioactive compound of
      Atractylodes macrocephula Koidz atractylenolide 1 (ATL-1) inhibited human lung
      cancer cell growth by suppressing the gene expression of 3-Phosphoinositide
      dependent protein kinase-1 (PDK1 or PDPK1). However, the potentially associated
      molecules and downstream effectors of PDK1 underlying this inhibition,
      particularly the mechanism for enhancing the anti-tumor effects of epidermal
      growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs), remain unknown.
      METHODS: Cell viability and cell cycle distribution were measured using 3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry
      assays, respectively. Western blot analyses were performed to examine the protein
      expressions of PDK1 and of zeste homolog 2 (EZH2). The levels of long non-coding
      RNA (lncRNA) and HOX transcript antisense RNA (HOTAIR) were examined via qRT-PCR.
      RNA-binding protein immunoprecipitation assays were used to analyze HOTAIR
      interaction with EZH2. The promoter activity of the EZH2 gene was determined
      using Secrete-Pair Dual Luminescence Assay Kit. Exogenous expressions of PDK1,
      HOTAIR, and EZH2 were conducted via transient transfection assays. A xenografted
      tumor model was used to further evaluate the effect of ATL-1 in the presence or
      absence of erlotinib in vivo. RESULTS: We showed that the combination of ATL-1
      and EGFR-TKI erlotinib further inhibited growth and induced cell arrest of the
      human lung cancer cells, determined by both MTT and flow cytometry assays. ATL-1
      inhibited the protein expression and the promoter activity of EZH2, which was
      reversed in cells with PDK1 overexpression. Interestingly, ATL-1 inhibited the
      expression levels of HOTAIR. While silencing HOTAIR inhibited the expressions of
      PDK1 and EZH2, overexpression of HOTAIR reduced the ATL-1-reduced PDK1 and EZH2
      protein expressions and EZH2 promoter activity. In addition, ATL-1 reduced the
      HOTAIR binding to the EZH2 protein. Moreover, we found that exogenously expressed
      EZH2 antagonized the effect of ATL-1 on cell growth inhibition. Consistent with
      the in vitro results, ATL-1 inhibited tumor growth and the expression levels of
      HOTAIR, protein expressions of EZH2 and PDK1 in vivo. Importantly, there was
      synergy of the combination of ATL-1 and erlotinib in this process. CONCLUSION:
      Here, we provide the first evidence that ATL-1 inhibits lung cancer cell growth
      through inhibiting not only the PDK1 but also the lncRNA HOTAIR, which results in
      the reduction of one downstream effector EZH2 expression. The novel interplay
      between the HOTAIR and EZH2, as well as repressions of the PDK1 and HOTAIR
      coordinate the overall effects of ATL-1. Importantly, the combination of ATL-1
      and EGFR-TKI erlotinib exhibits synergy. Thus, targeting the PDK1- and HOTAIR
      mediated downstream molecule EZH2 by the combination of ATL-1 and erlotinib
      potentially facilitates the development of an additional novel strategy to combat
      lung cancer.

PMID- 30223278
TI  - Application of the Milan System for Risk Stratification and Its Comparison with a
      Previous Reporting System of Parotid Gland Cytopathology in a Tertiary Care
      Centre.
AB  - OBJECTIVE: To compare the recently proposed Milan System for Reporting Salivary
      Gland Cytopathology (MSRSGC) with the four-tiered reporting system (FTRS)
      followed at our institute. METHODS: Parotid gland fine-needle aspirates reported
      over a period of 5 years were analysed. These aspirates had been placed into 4
      categories according to the FTRS: unsatisfactory (UNS), no evidence of
      malignancy/negative (NEG), inconclusive for malignancy (INC), and diagnostic for
      malignancy/positive (POS). Aspirates with follow-up histopathology were then
      categorized according to the MSRSGC as follows: non-diagnostic, non-neoplastic,
      atypia of unde-termined significance (AUS), neoplasm, suspicious for malignancy,
      and malignant. The risk of malignancy (ROM) was calculated. RESULTS: A total of
      893 parotid region aspirates were evaluated and histopathology was available for
      190 cases (21%). ROM in MSRSGC groups, namely non-diagnostic, non-neoplastic,
      AUS, neoplasm, suspicious for malignant neoplasm, and malignant, was 44, 8, 0,
      12, 81 and 100%, respectively. ROM in FTRS groups, namely UNS, NEG, INC, and POS,
      was 45, 13, 67 and 100%, respectively. CONCLUSIONS: MSRGC and FTRS are comparable
      with respect to the ROM across groups. Compared to FTRS, the further
      subcategorisation of the non-malignant group, the use of specific nomenclature,
      and the reproducibility of MSRGC provide proper risk stratification, thereby
      guiding better management and resulting in improved patient care.

PMID- 30223279
TI  - Anatomy Revisited: Hemodialysis Catheter Malposition into the Chest.
AB  - In most situations, central catheters are implanted in the right jugular vein as
      initial access for hemodialysis. However, after repeated punctures, the proximal
      vessels become stenosed and thrombosed and misplacement is likely to occur.
      Correct catheter position in the vein can be easily ascertained with X-ray or
      cross-sectional CT imaging. In this report, we describe the case of a 77-year-old
      patient on chronic hemodialysis via catheter due to arteriovenous fistula
      dysfunction. We placed a cuffed-tunneled hemodialysis catheter in the left
      internal jugular vein. Malpositioning of the catheter led to perforation of the
      great veins and migration of the catheter tip into the chest. It is important to
      be aware of the risk of potential incorrect positioning of dialysis catheters.
      Due to the stenosis and fragility of the vessel wall, perforation may occur. In
      cases of doubt, correct placement of large-bore catheters via the internal
      jugular vein should be verified by means of appropriate imaging before
      hemodialysis is performed.

PMID- 30223281
TI  - Effect of Different Methods of Administration of Diltiazem on Clinical Efficacy
      in Patients with Acute ST-Segment Elevation Myocardial Infarction.
AB  - BACKGROUND The aim of this study was to investigate the optimal route of
      administration of diltiazem in emergency PCI and to provide the best clinical
      treatment for ASTEMI patients. MATERIAL AND METHODS A total of 90 patients with
      ASTEMI treated in our hospital from January 2015 to January 2016 were selected.
      Prior to thrombus aspiration, a thrombus aspiration catheter was used to perform
      diltiazem injection at the distal end of the infarct-related artery (IRA). We
      chose the acute ST-elevation myocardial infarction (ASTEMI) patients treated with
      direct PCI to compare different administration routes of diltiazem. The
      occurrence of major adverse cardiac events (MACEs) was closely observed during
      hospitalization and was obtained through outpatient visits or telephone follow
      ups over the next 6 months. RESULTS Intracoronary infusion of diltiazem at the
      distal end of the culprit vessel, compared to conventional coronary mouth and
      intravenous injection, was significantly improved in thrombolysis in myocardial
      infarction (TIMI) frame count immediately after PCI stent implantation, ST
      segment drop rate after 90 min, and left ventricular ejection fraction (LVEF)
      after 1 week. Furthermore, the peak value of high-sensitivity cardiac troponin I
      (hs-cTnI), a marker for myocardial injury, was the lowest. White blood cell
      count, neutrophil count, mean platelet volume (MPV), and high-sensitivity C
      reactive protein (hs-CRP) were significantly lower than with the other 2
      administration routes, and there was no effect on intracoronary pressure or heart
      rate. CONCLUSIONS Patients with ASTEMI who underwent emergency PCI treatment had
      good clinical outcomes using intracoronary diltiazem at the distal end of the
      culprit vessel.

PMID- 30223280
TI  - Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha
      Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive
      Proteomic and Metabolomic Signatures.
AB  - BACKGROUND/AIMS: Cholestasis is the major cause of the accumulation of bile acids
      and results in liver damage, fibrosis, and failure. A growing number of studies
      have shown that gentiopicroside is a promising prospect that may protect the
      liver. However, its therapeutic mechanism has not yet been clarified. This study
      aimed to explore the effect and mechanism of gentiopicroside in cholestasis
      induced by alpha-naphthylisothiocyanate. METHODS: We performed isobaric tags for
      relative and absolute quantification-based quantitative proteomics and
      metabolomics using liquid chromatography quadruple time-of-fight mass
      spectrometry and identified the expression of 73 metabolites and 84 proteins
      associated with cholestasis-related dysfunctions in the metabolism of bile acids,
      fatty acids, and glycerophospholipids. RESULTS: Integrated analyses of proteomic
      and metabonomic studies showed altered pathways in cholestasis-induced liver
      injury involving increased activity of farnesoid X receptor/retinoid X receptor,
      bile acid biosynthesis, and peroxisome proliferator-activated receptor
      alpha/retinoid X receptor-alpha. Gentiopicroside could reverse these metabolite,
      protein, and blood biochemical indices, as well as alleviate liver damage. The
      progressive changes in the proteins and genes may be correlated with cholestasis
      and were confirmed by western blot and quantitative realtime polymerase chain
      reaction. CONCLUSION: Gentiopicroside could be used to protect the liver in the
      presence of cholestasis.

PMID- 30223282
TI  - Doppler ultrasound surveillance of TIPS-patency in the era of covered stents -
      retrospective analysis of a large single-center cohort.
AB  - PURPOSE: The purpose of this study was to determine accuracy and necessity of
      long-term Doppler ultrasound (DU) surveillance of transjugular intrahepatic
      portosystemic shunt (TIPS) patency after implantation of an ePTFE-covered stent
      graft (Viatorr). METHODS: This single-center retrospective study includes 228
      consecutive cirrhotic patients with TIPS implantation due to portal hypertensive
      complications. Standardized DU surveillance was scheduled 3 - 5 days, 3 months,
      and 6 months after TIPS implantation and every 6 months thereafter. Portal
      venography was performed in case of DU findings suspicious of TIPS dysfunction,
      clinical signs of recurrent portal hypertension, or refractory hepatic
      encephalopathy. RESULTS: During a mean follow-up of 16.6 +/- 23.4 months, 866 DU
      examinations were performed. Twenty-two cases of TIPS dysfunction were observed
      in 16 patients with no first dysfunction more than 4 years after implantation.
      Routine DU in asymptomatic patients had little therapeutic impact (0.75 %). DU
      and venography were concordant in 39/46 (84.8 %) paired examinations, and 1-, 2-,
      and 5-year primary TIPS patency was 87.4 %, 83.7 %, and 79.97 %, respectively.
      Patients with TIPS dysfunction and subsequent successful revision during the
      first 2 years of follow-up had a significantly higher risk (p = 0.001) of new
      dysfunction compared to those without TIPS dysfunction. Cumulative 1-, 2-, and 5
      year survival was 68.7 %, 61.3 %, and 42.7 %, respectively. CONCLUSIONS: Despite
      acceptable accuracy, scheduled DU surveillance proved to have minor therapeutic
      impact. Thus, detailed DU surveillance is not useful in asymptomatic patients
      after 2 years of unremarkable follow-up. In contrast, long-term DU surveilleance
      should be performed in patients after successful revision of TIPS dysfunction and
      patients with prothrombotic states (e. g., portal vein thrombosis, Budd-Chiari
      syndrome).

PMID- 30223283
TI  - [The role of abdominal ultrasound in hematological diseases].
AB  - At the time of primary diagnosis, hematological diseases often present with
      unspecific symptoms, and abdominal sonography is performed as part of the initial
      diagnostic work-up. The detection of an enlarged spleen, of pathological lymph
      nodes or of other findings may help to suspect hematological diseases. Also, in
      case of suspected lymph node enlargement, sonography may be a first step. If
      detection of enlarged and pathological lymph nodes leads to suspicion of
      malignant lymphomas, examination of further lymph node stations may give an
      initial impression of the stage of disease and can help in planning further
      diagnostic strategies. Due to its wide availability, the feasibility of bedside
      examination, lack of radiation exposure and easy repeatability, sonographic
      examinations may also play an important role in the initial work-up of anemia,
      leucopenia, leukocytosis, and thrombopenia as well as for the detection of
      complications when following up on hematological diseases.

PMID- 30223284
TI  - [Relamorelin in patients with diabetic gastroparesis].

PMID- 30223285
TI  - RNASEH2B Pathogenic Gene Variant in Uncomplicated Hereditary Spastic Paraplegia:
      Report of a New Patient.

PMID- 30223286
TI  - Monitoring Criteria of Intracranial Lesions in Children Post Mild or Moderate
      Head Trauma.
AB  - Head injury is the most common cause of child traumatology. However, there exist
      no treatment guidelines in children having intracranial lesions due to minor or
      moderate head trauma. There is little knowledge about monitoring, clinical
      exacerbation risk factors, or optimal duration of hospitalization. The aim of
      this retrospective study is to find predictive factors in the clinical course of
      non-severe head trauma in children, and thus to determine an optimal management
      strategy. Poor clinical progress was observed in only 4 out of 113 children. When
      there are no clinical signs and no eating disorders, an earlier discharge is
      entirely appropriate. Nevertheless, persistent clinical symptoms including
      headache, vomiting, and late onset seizure, especially in conjunction with
      hemodynamic disorders such as bradycardia, present a risk of emergency
      neurosurgery or neurological deterioration. Special attention should be paid to
      extradural hematoma (EDH) of more than 10 mm, which can have the most severe
      consequences. Clinical aggravation does not necessarily correlate with a change
      in follow-up imaging. Conversely, an apparent increase in the brain lesion on the
      scan is not consistently linked to a pejorative outcome.

PMID- 30223287
TI  - Effects of Parathyroidectomy on Plasma iPTH and (1-84) PTH Levels in Patients
      with Stage 5 Chronic Kidney Disease.
AB  - Currently, the second-generation intact parathyroid hormone (iPTH) assay is
      commonly used for measuring PTH levels. The iPTH assay detects both full-length
      (1-84)PTH and (7-84)PTH fragments, which have antagonistic effects on (1-84)PTH
      in bones and kidneys. The third-generation PTH assay is specific for (1-84)PTH.
      This study examined the features of different PTH fragments in stage 5 chronic
      kidney disease (CKD) and the effects of parathyroidectomy (PTX) on the above
      markers in severe secondary hyperparathyroidism (SHPT) patients. The cross
      sectional study included 262 stage 5 CKD patients and 90 controls. A prospective
      follow-up study was then conducted in 34 PTX patients. Second- and third
      generation assays were used to measure plasma iPTH and (1-84)PTH levels,
      respectively. Circulating (7-84)PTH levels were calculated by subtracting the (1
      84)PTH value from the iPTH value. Different plasma PTH fragments were higher, and
      (1-84)PTH/iPTH was lower in CKD patients than in controls. Plasma (1-84)PTH and
      (7-84)PTH concentrations increased as iPTH levels increased, and (7-84)PTH
      increased more evidently. Plasma iPTH, (1-84)PTH and (7-84)PTH levels were 1530.5
      (885.0-2111.5) pg/ml, 683.1 (431.4-1018.0) pg/ml, and 739.3 (452.6-1261.0) pg/ml,
      respectively, in PTX patients. Plasma iPTH, (1-84)PTH and (7-84)PTH
      concentrations decreased considerably, and the (1-84)PTH/iPTH ratio increased
      after PTX (median follow-up interval: 10.9 months). Stage 5 CKD patients had
      higher plasma levels of different PTH fragments, and lower (1-84)PTH/iPTH ratio.
      PTX could significantly reverse these abnormalities in severe SHPT patients. The
      iPTH assay overestimated the function of the parathyroid glands; thus, the third
      generation PTH assay is likely better for the management of CKD patients.

PMID- 30223288
TI  - The Roles of IL-10 Gene Polymorphisms in Diabetes Mellitus and Their Associated
      Complications: A Meta-Analysis.
AB  - The roles of interleukin-10 (IL-10) gene polymorphisms in diabetes mellitus (DM)
      have been intensively analyzed earlier, but the results of these studies were
      conflicting. Hence, we performed this study to better assess the relationship
      between IL-10 genetic variations and DM. Eligible studies were searched in
      PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess correlations between IL-10
      polymorphisms and DM. A total of 32 studies were finally included in our
      analyses. Significant associations with the risk of DM were detected for the
      rs1800871, rs1800872, and rs1800896 polymorphisms. As for complications in DM,
      significant association with the risk of diabetic nephropathy (DN) was detected
      for the rs1800871 polymorphism. In addition, we also found that the rs1800896
      polymorphism was significantly associated with the risk of diabetic retinopathy
      (DR). Further stratified analyses on the basis of type of disease demonstrated
      that the positive results were predominantly driven by the T2DM subgroup. When we
      stratified data based on ethnicity of participants, we found that the rs1800871
      polymorphism was significantly correlated with DM in Caucasians, the rs1800872
      polymorphism was significantly correlated with DM in Asians, and the rs1800896
      polymorphism was significantly correlated with DM in both Caucasians and Asians.
      Our findings indicate that rs1800871, rs1800872, and rs1800896 polymorphisms may
      serve as genetic biomarkers of DM. Moreover, the rs1800871 and rs1800896
      polymorphisms may also contribute to the development of complications in DM.

PMID- 30223289
TI  - Association of Irisin Circulating Level with Diabetic Retinopathy: A Case-Control
      Study.
AB  - Obesity and obesity induced diabetes (DM II) development and progression have
      been associated with sedentary lifestyle. Irisin, a newly discovered myokine, has
      been demonstrated at lower levels in obese and DM II patients compared to
      controls. The main aim of this study is to explore association of Irisin with
      diabetic retinopathy (DR). A total of 233 healthy and DM II adults participated
      in this study. Participants were divided into four categories: a healthy control
      group and an age-match subset of patients with DM II; a positive control group of
      patients with DM II not affected by DR (No DR); and patients with DM II affected
      by DR (non-proliferative DR (NPDR) and proliferative DR (PDR)). Plasma samples
      were quantified for Irisin measurement, lipid profile and HbA1c. Comparison of
      the age-matched groups of healthy controls and patients with DM II revealed lower
      Irisin plasma level in DM II group. Analyses revealed negative correlations of
      Irisin to HbA1c and LDL levels and positive correlation to HDL level. Comparing
      Irisin level in No DR and DR groups revealed a higher level in No DR group and
      analysis per DR classification indicated higher Irisin level in NPDR group. Our
      results demonstrate not only correlation of plasma Irisin level with DR stages,
      but also significantly different Irisin level among them. This is promising in
      terms of researching Irisin as a potential associating marker for DM II and DR
      development and progression.

PMID- 30223290
TI  - Concomitant Occlusive Vascular Lesions of Legs in Patients with Degenerative
      Lumbar Diseases: Do These Lesions Influence Treatment?
AB  - BACKGROUND AND STUDY AIMS:  Vascular narrowing or obstruction reduces blood flow
      to the lower limbs during exercise or at rest. Symptoms may range from
      intermittent claudication to pain at rest. Narrowing of these arteries may
      produce pain in the buttocks, thighs, or legs. These symptoms may resemble those
      of lumbar radicular pain. Spine surgeons may overlook obstructive vascular
      lesions of the lower limbs in patients with lumbar degenerative diseases such as
      spinal stenosis and spondylolisthesis. We investigated the clinical and
      radiologic risk factors of concomitant vascular pathologic lesions in patients
      with degenerative lumbar diseases. MATERIALS AND METHODS:  If patients presented
      with a weak or absent dorsalis pedis artery pulse, edema of both legs, and a past
      history related to vascular lesions of the lower limbs, we evaluated the veins
      and arteries of the lower extremities using Doppler sonography. If abnormal
      vascular findings were detected, computed tomography angiography (CTA) of the
      lower extremities was performed. Radiologic and clinical risk factors of
      concomitant occlusive arterial lesions of the lower limb were analyzed by
      logistic regression analysis. RESULTS:  In 2013, 335 patients suspected of having
      vascular lesions underwent Doppler sonography. Among them, CTA of the lower
      extremities was performed in 58 patients. The mean age was 69.4 years (35 men and
      23 women). Severe narrowing or total occlusion of the leg arteries was detected
      in 23 patients. Partial obstructive arterial disease of the legs was detected in
      14 patients. Occlusion but with good collateral circulation of the leg was found
      in three patients. Surgical treatment plans were cancelled or changed in 28
      patients. The risk factors for occlusive arterial lesions of the legs were an
      abnormal ankle-brachial pressure index (ABPI), absent dorsalis pedis artery
      pulse, and lack of response after a pain-blocking procedure. CONCLUSION:  If
      patients present with a weak or absent dorsalis pedis artery pulse, abnormal ABPI
      ratio, and no response after a pain-blocking procedure, the clinician should
      consider the possibility of severe arterial occlusion of the legs. We suggest
      that the differential diagnosis of obstructive arterial lesions of the legs from
      lumbar degenerative diseases is important to prevent unnecessary invasive
      surgical treatment of the lumbar spine.

PMID- 30223292
TI  - EIciRNA-mediated gene expression: tunability and bimodality.
AB  - Biological experiments have verified that EIciRNAs (a class of circRNA) produced
      from pre-mRNA can regulate gene expression, but the effect of regulation remains
      unexplored. Here, we refine a mechanistic gene model from experimental facts, in
      which we assume pre-mRNA synthesizes EIciRNAs and mRNAs in a probabilistic
      manner, with the probability called the pathway strength, and the resulting
      EIciRNAs positively regulate the pre-mRNA synthesis. We show that there is a
      critical pathway strength such that the mRNA mean and the mRNA noise reach the
      highest and lowest levels, respectively. The EIciRNA can induce the unimodal and
      bimodal mRNA expressions, as well as the transition between them. Our
      investigation hints that EIciRNA is a non-negligible factor affecting cell-to
      cell variability in gene expression.

PMID- 30223291
TI  - Longitudinally monitoring of P-III-NP, IGF-I, and GH-2000 score increases the
      probability of detecting two weeks' administration of low-dose recombinant growth
      hormone compared to GH-2000 decision limit and GH isoform test and micro RNA
      markers.
AB  - To detect doping with growth hormone (GH), GH isoform and biomarkers tests are
      available. Both methods use population-based decision limits. Future testing in
      anti-doping is progressing toward individual-based reference ranges, and it is
      possible that with such an approach the sensitivity to detect GH doping may
      increase. In addition to monitoring different proteins, the use of miRNAs as
      future GH biomarkers has been discussed. Here we have longitudinally studied the
      serum concentrations of IGF-I, P-III-NP and the different GH isoforms in nine
      healthy men prior to, during and after two weeks' administration with low doses
      (1 and 4 IU/day) of recGH. Moreover, three putative miRNAs were analyzed. The
      results show that 80% of the participants were identified as atypical findings
      using the GH isoform test. However, the participants were only positive 1.5-3
      hours directly after an injection. Only one of the participants reached a GH-2000
      score indicative of doping when a population-based decision limit was applied.
      When IGF-I and P-III-NP were longitudinally monitored, 88% of the participants
      were identified above an individual upper threshold arbitrarily calculated as
      three standard deviations above the mean values of four baseline samples. The
      miRNA levels displayed large intra-subject variations that did not change in
      relation to recGH administration. Our results show that the GH isoform test is
      very sensitive in detecting low doses of recGH but with a short detection window.
      Moreover, longitudinally monitoring of IGF-I and P-III-NP may be a promising
      future approach to detect GH doping.

PMID- 30223293
TI  - Pyemotes ventricosus detection in a baby skin folds.

PMID- 30223294
TI  - Refractory juvenile myoclonic epilepsy: a meta-analysis of prevalence and risk
      factors.
AB  - BACKGROUND AND PURPOSE: Juvenile myoclonic epilepsy (JME) is a common epilepsy
      syndrome for which treatment response is generally assumed to be good. We aimed
      to determine the prevalence and prognostic risk factors for refractoriness of
      JME. METHODS: We systematically searched PubMed and EMBASE and included 43
      eligible studies, reporting seizure outcome after antiepileptic drug (AED)
      treatment in JME cohorts. We defined refractory JME as persistence of any seizure
      despite AED treatment and performed a random-effects meta-analysis to assess the
      prevalence of refractory JME and of seizure recurrence after AED withdrawal in
      individuals with well-controlled seizures. Studies reporting potential prognostic
      risk factors in relation to seizure outcome were included for subsequent meta
      analysis of risk factors for refractoriness. RESULTS: Overall, 35% (95%
      confidence interval, 29-41%) of individuals (n = 3311) were refractory. There was
      marked heterogeneity between studies. Seizures recurred in 78% (95% confidence
      interval, 52-94%) of individuals who attempted to withdraw from treatment after a
      period of seizure freedom (n = 246). Seizure outcome by publication year
      suggested that prognosis did not improve over time. Meta-analysis suggested six
      variables as prognostic factors for refractoriness, i.e. having three seizure
      types, absence seizures, psychiatric comorbidities, earlier age at seizure onset,
      history of childhood absence epilepsy and praxis-induced seizures. CONCLUSION:
      One-third of people with JME were refractory, which is a higher prevalence than
      expected. Risk factors were identified and can be used to guide treatment and
      counselling of people with JME.

PMID- 30223295
TI  - Potential landscape-scale pollinator networks across Great Britain: structure,
      stability and influence of agricultural land cover.
AB  - Understanding spatial variation in the structure and stability of plant
      pollinator networks, and their relationship with anthropogenic drivers, is key
      for maintaining pollination services and mitigating declines. Constructing
      sufficient networks to examine patterns over large spatial scales remains
      challenging. Using biological records (citizen science), we constructed potential
      plant-pollinator networks at 10 km resolution across Great Britain, comprising
      all potential interactions inferred from recorded floral visitation and species
      co-occurrence. We calculated network metrics (species richness, connectance,
      pollinator and plant generality) and adapted existing methods to assess
      robustness to sequences of simulated plant extinctions across multiple networks.
      We found positive relationships between agricultural land cover and both
      pollinator generality and robustness to extinctions under several extinction
      scenarios. Increased robustness was attributable to changes in plant community
      composition (fewer extinction-prone species) and network structure (increased
      pollinator generality). Thus, traits enabling persistence in highly agricultural
      landscapes can confer robustness to potential future perturbations on plant
      pollinator networks.

PMID- 30223296
TI  - Revealing the metabolic characteristics of human embryonic stem cells by genome
      scale metabolic modeling.
AB  - Embryonic stem cells (ESCs) are characterized by a dual capacity, self-renewal
      and pluripotency, which can be regulated by metabolism. A better understanding of
      ESC metabolism and regulatory mechanisms is pivotal for research into
      development, ageing, and cancer treatment. However, a systematic and
      comprehensive delineation of human ESC metabolism is still lacking. Here, we
      reconstructed the first genome-scale metabolic model (GEM) of human ESCs (hESCs).
      By GEM simulation and analyses, hESC global metabolic characteristics including
      essential metabolites and network motifs were identified. Potential metabolic
      subsystems responsible for self-renewal and pluripotency were also identified by
      analyses and experiments. This first GEM of hESCs provides a novel view and
      resource for stem cell metabolism research and will contribute to the elucidation
      of their metabolic characteristics.

PMID- 30223298
TI  - Coexisting pituitary and non-pituitary gigantism in the same family.

PMID- 30223297
TI  - Nurses and health-promoting self-care: Do we practice what we preach?
AB  - AIMS: To examine the health-promoting behaviours performed by registered nurses
      (RNs), as well as workplace factors that influence participation in those
      behaviours. BACKGROUND: Nurses have high levels of overweight/obesity and may not
      be engaging in health-promoting self-care. METHODS: A cross-sectional Web-based
      survey collected information from 335 RNs regarding their physical activity,
      sedentariness and fruit/vegetable consumption. RESULTS: More than half were
      overweight (34.1%) or obese (23.4%), and 80.1% were "sedentary" (>=3 hr
      sitting/day), particularly those working outside of direct patient care in
      management, research and education. Only 47.2% consumed 5+ servings of
      fruits/vegetables daily. Nurses who enjoyed their jobs (higher levels of
      compassion satisfaction) reported higher levels of physical activity (p = 0.03)
      and fruit/vegetable consumption (p = 0.02). CONCLUSION: RNs who work outside of
      direct patient care might be at increased risk for sedentariness and obesity. RNs
      who enjoy their jobs may experience less stress and have more energy to exercise
      and to prepare/consume healthy meals. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse
      managers should practice self-care by engaging in exercise, proper nutrition and
      demonstrating work-life balance, both to protect their own health and to serve as
      role models for RNs in direct patient care.

PMID- 30223299
TI  - Characteristics of Pediococcus pentosaceus Q6 isolated from Elymus nutans growing
      on the Tibetan Plateau and its application for silage preparation at low
      temperature.
AB  - AIMS: Characteristics of a strain Pediococcus pentosaceus Q6 isolated from Elymus
      nutans growing on the Tibetan plateau and its effects on E. nutans silage
      fermentation stored at low temperature were investigated. METHODS AND RESULTS:
      Sugar fermentation pattern and growth profiles of the strain Q6 and its reference
      strain APP were characterized. The strain Q6 and APP were inoculated to E. nutans
      at ensiling respectively; and ensiled at different temperatures (10, 15 and 25
      degrees C) for 30, 60 and 90 days. The results indicated that Q6 could grow at pH
      3.0 and at 4 degrees C. In contrast to APP, Q6 could ferment mannitol,
      saccharose, sorbitol and rhamnose. Lower pH in Q6-treated silages fermented for
      60 days at 10 and 15 degrees C was found compared with the control and APP
      treated groups. For the silages that were stored at 10 or 15 degrees C, the
      greatest lactic acid content were detected in Q6-inoculated silages ensiled for
      30 and 60 days respectively. There were no differences in pH and lactic acid
      content between Q6- and APP-treated silages ensiled at 10 and 15 degrees C for 90
      days respectively. CONCLUSIONS: Inoculation of the strain P. pentosaceus Q6 could
      improve fermentation quality of ensiled E. nutans at the early stage of ensiling
      stored at low temperature (10 or 15 degrees C). SIGNIFICANCE AND IMPACT OF THE
      STUDY: The selection of P. pentosaceus inoculants for improving silage quality at
      low temperature, which provides a candidate strain to make high-quality silage in
      regions with frigid climate.

PMID- 30223300
TI  - Diagnostic performance of HMGA2 gene expression for differentiation of malignant
      thyroid nodules: A systematic review and meta-analysis.
AB  - OBJECTIVE: The purpose of the current study was to investigate the diagnostic
      performance of high mobility group A2 (HMGA2) gene expression for differentiation
      of malignant thyroid nodules through a systematic review and meta-analysis.
      DESIGN: The MEDLINE/PubMed and EMBASE database, from the earliest available date
      of indexing through 10 April 2018, were searched for studies evaluating the
      diagnostic performance of HMGA2 expression for differentiation of thyroid
      nodules. METHODS: We determined the sensitivities and specificities across
      studies, calculated positive and negative likelihood ratios (LR+ and LR-), and
      constructed summary receiver operating characteristic (ROC) curves. RESULTS:
      Across 7 studies, the pooled sensitivity for HMGA2 expression was 0.78 (95% CI;
      0.67-0.86) with heterogeneity (I2  = 86.6) and a pooled specificity of 0.94 (95%
      CI: 0.85-0.98) with heterogeneity (I2  = 94.7). Likelihood ratio (LR) syntheses
      gave an overall positive likelihood ratio (LR+) of 12.6 (95% CI: 5.1-31.3) and
      negative likelihood ratio (LR-) of 0.24 (95% CI: 0.15-0.36). The pooled
      diagnostic odds ratio (DOR) was 53 (95% CI: 18-159). Hierarchical summary ROC
      curve indicates that the areas under the curve were 0.92 (95% CI: 0.89-0.94). In
      meta-regression analysis, no definite variable was the source of the study
      heterogeneity. CONCLUSION: The current meta-analysis showed the moderate
      sensitivity and high specificity of HMGA2 expression for differentiation of
      malignant thyroid nodules. The likelihood ratio scatter-gram suggested that HMGA2
      expression analysis could be useful for confirmation of the presence of malignant
      thyroid nodules. Considering the heterogeneity of included studies, further large
      prospective studies are necessary to confirm these results.

PMID- 30223301
TI  - Late activation of the Raf/MEK/ERK pathway is required for translocation of the
      respiratory syncytial virus F protein to the plasma membrane and efficient viral
      replication.
AB  - Activation of the Raf/MEK/ERK cascade is required for efficient propagation of
      several RNA and DNA viruses, including human respiratory syncytial virus (RSV).
      In RSV infection, activation of the Raf/MEK/ERK cascade is biphasic. An early
      induction within minutes after infection is associated with viral attachment.
      Subsequently, a second activation occurs with, so far, unknown function in the
      viral life cycle. In this study, we aimed to characterise the role of Raf/MEK/ERK
      mediated signalling during ongoing RSV infection. Our data show that inhibition
      of the kinase MEK after the virus has been internalised results in a reduction of
      viral titers. Further functional investigations revealed that the late-stage
      activation of ERK is required for a specific step in RSV replication, namely, the
      secretory transport of the RSV fusion protein F. Thus, MEK inhibition resulted in
      impaired surface accumulation of the F protein. F protein surface expression is
      essential for efficient replication as it is involved in viral filament
      formation, cell fusion, and viral transmission. In summary, we provide detailed
      insights of how host cell signalling interferes with RSV replication and
      identified the Raf/MEK/ERK kinase cascade as potential target for novel anti-RSV
      strategies.

PMID- 30223302
TI  - Bleeding after paracentesis in patients with decompensated cirrhosis and acute
      kidney injury: The perfect storm.

PMID- 30223303
TI  - Morphological classification system of hair regrowth patterns in alopecia areata
      patches: DIMT classification.

PMID- 30223304
TI  - Continuous cardiometabolic risk score definitions in early childhood: a scoping
      review.
AB  - BACKGROUND: Cardiometabolic risk (CMR) in young children has been measured using
      various approaches, including a continuous summary score that incorporates
      components such as adiposity, lipids, metabolic factors and blood pressure.
      OBJECTIVES: The objective of this study was to comprehensively review definitions
      of continuous CMR scores in children <10 years of age. METHODS: A scoping review
      was conducted using a systematic search of four scientific databases up to June
      2016. Inclusion criteria were children <10 years of age and report of a
      continuous CMR score. RESULTS: Ninety-one articles were included. Most studies
      were published from 2007 to 2016 (96%). Nearly all continuous CMR scores (90%)
      were calculated using the sum or the mean of z-scores, and many articles age
      standardized and sex-standardized components within their own population. The
      mean number of variables included in the risk scores was 5 with a range of 3-11.
      The most commonly included score components were waist circumference (52%),
      triglycerides (87%), high-density lipoprotein cholesterol (67%), glucose (43%)
      and systolic blood pressure (52%). IMPORTANCE: Continuous CMR scores are emerging
      frequently in the child health literature and are calculated using numerous
      methods with diverse components. This heterogeneity limits comparability across
      studies. A harmonized definition of CMR in childhood is needed.

PMID- 30223305
TI  - Co-Prescription of Strong CYP1A2 Inhibitors and the Risk of Tizanidine-Associated
      Hypotension: A Retrospective Cohort Study.
AB  - Tizanidine, a widely used muscle relaxant that can lower blood pressure, is
      metabolized by the cytochrome P450 1A2 (CYP1A2). We studied 1,626 patients
      prescribed tizanidine and 5,012 prescribed cyclobenzaprine concurrently with a
      strong CYP1A2 inhibitor. The primary outcome was severe hypotension, defined as
      systolic blood pressure (SBP) <= 70 mmHg during periods of drug co-exposure.
      Severe hypotension occurred more often in the tizanidine group (2.03%; n = 33)
      than the cyclobenzaprine group (1.28%; n = 64); odds ratio (OR) = 1.60; P =
      0.029. This difference remained statistically significant after adjustment for a
      log-transformed propensity score that included age, sex, race, Charlson's
      comorbidity index, and concurrent use of antihypertensive medications (OR = 1.57;
      P = 0.049). A sensitivity analysis that defined hypotension as SBP < 90 mmHg also
      yielded higher rates of hypotension among patients prescribed tizanidine. In
      conclusion, CYP1A2 inhibition increases the risk of hypotensive episodes
      associated with the use of tizanidine in routine clinical practice.

PMID- 30223306
TI  - Modification of the prolonged mechanical ventilation prognostic model score to
      predict short-term and 1-year mortalities.
AB  - BACKGROUND AND OBJECTIVE: We aimed to validate the use of the Prolonged
      Mechanical Ventilation Prognostic Model (ProVent) score in medically ill patients
      with co-morbidities and to modify the score to improve the prediction power of 1
      year mortality. METHODS: We conducted a retrospective study of all patients who
      required at least 14 days of mechanical ventilation (MV) and established two
      groups (14-20 and >=21 days of MV) based on the MV duration. We performed
      external validation of the present ProVent Model in our patients on Day 14 (or
      Day 21 for the >=21-day MV group) of MV, and established the extended ProVent
      model, while considering the albumin and bilirubin levels and co-morbidities
      (chronic obstructive pulmonary disease and cancer). RESULTS: A total of 1288
      patients (666 and 622 with 14-20 and >=21 days of MV, respectively) with at least
      14 days of MV were enrolled. The 1-year mortality was 79.9% and 78.7% in the >=21
      and 14-20-day groups, respectively. Most of the observed mortality rates in all
      groups were within the 95% CI of predicted mortality as per the ProVent Model,
      except for the ProVent scores of 0 and 5. In the ProVent model, the area under
      the curve for the prediction of 1-year mortality was 0.69 in all patients with
      >=14 days of MV, whereas in the extended ProVent model, the area under the curve
      was 0.89. CONCLUSION: The extended ProVent model, which considers co-morbidities
      and laboratory data, increases the prediction power of 1-year mortality in
      patients who require prolonged MV.

PMID- 30223307
TI  - Screening for syphilis with dual algorithms: analysis of discordant and
      concordant serology results in a population with a low prevalence of syphilis.
AB  - BACKGROUND: Currently, many laboratories have switched the traditional screening
      algorithm (TSA) to reverse screening algorithm (RSA) for the efficiencies in high
      volume syphilis screening. However, confusions have been arisen regarding this
      paradigm shift. OBJECTIVE: To compare the performance of two algorithms with head
      to-head mode. METHODS: Sera screening for syphilis were tested in parallel with
      chemiluminescence immunoassay (CIA) and toluidine red unheated serum test
      (TRUST). CIA-reactive sera from the RSA were reflexively tested with TRUST and
      confirmed with Treponema pallidum particle agglutination assay (TPPA), while the
      TRUST-reactive serology from the TSA were afterwards tested with TPPA. RESULTS: A
      total of 110 663 serum samples were screened. The RSA identified 2259 (2.0%) CIA
      reactive results, of which 377 (16.7%) showed TPPA nonreactive results, while the
      TSA identified 934 (0.8%) TRUST-reactive results, of which 67 (7.2%) showed TPPA
      nonreactive results. Among the 2259 CIA-reactive results, 1392 (61.6%) were TRUST
      nonreactive, of which 350 (25.1%) were TPPA-nonreactive. A total of 182 sera from
      the 350 TPPA-nonreactive sera were further tested by a second CIA (VITROS
      Syphilis TPA, VITROS TPA), of which 155 (85.2%) were nonreactive and 27 (14.8%)
      were reactive. The 27 VITROS TPA-reactive sera were further tested with a
      treponemal Western blot assay (Euroimmun IgG Western Blot, EuroWB), of which 11
      (41%) were indeterminate, 6 (22%) were nonreactive and 10 (37%) were reactive.
      Among the 10 EuroWB-reactive sera, two seroconverted to TPPA 1:80+/- after 1-year
      follow-up. Of 867 CIA-reactive/TRUST-reactive results, 27 (3.1%) were TPPA
      nonreactive. CONCLUSIONS: The RSA identified more patients with reactive
      treponemal serology. However, it also yielded an increased likely false-reactive
      rate compared with the TSA, especially those results with low index values and
      TRUST-nonreactive serology, were necessary to retest with a second treponemal
      test. Further testing results with TPPA, VITROS TPA and EuroWB suggested the
      false-reactive CIA screening results and the likely false-nonreactive TPPA
      results when the reactive treponemal results screened with RSA were to be
      identified.

PMID- 30223308
TI  - Improving discharge planning using the re-engineered discharge programme.
AB  - AIMS: (a) Assess nurses' readiness to learn (RTL) before receiving education on
      the re-engineered discharge (RED) programme and (b) measure utilization of the
      RED discharge process from patient chart reviews following an educational
      intervention. BACKGROUND: Preventable readmissions are of great concern. Rural
      areas are at a disadvantage, due to decreased access to health care and other
      disparities. METHODS: Sixty-nine participants completed the Self-Directed
      Learning Readiness Scale prior to the RED education intervention. Thirty-minute
      education interventions were provided addressing various learning preferences.
      RESULTS: Participants scored high M = 219.8 (SD 23.7) on the SDLR, indicating
      nurses' high RTL prior to educational intervention. Chart reviews found usage of
      the RED 12 actionable item pre-intervention, (n = 60) M = 6.55 (SD 1.478)
      compared to post-intervention (n = 60) M = 10.08 (SD 1.544) indicated
      statistically significant improvement in pre-discharge patient education and
      planning (t = 17.730, p = 0.000 [CI 3.13-3.93]). CONCLUSION: Current study found
      that nurses with higher levels of RTL who underwent RED educational sessions
      significantly improved delivery of the RED process documented in the medical
      record. IMPLICATIONS FOR NURSING MANAGEMENT: Those responsible for education
      initiatives must make understanding nurses' learning preferences a priority to
      improve the quality of bedside practice.

PMID- 30223309
TI  - External cephalic version at term: a cohort study of 18 years' experience.
AB  - OBJECTIVE: To analyse the outcome of referrals for external cephalic version
      (ECV). DESIGN: Retrospective cohort study of prospectively collected data.
      SETTING: Major university hospital, UK. SAMPLE: Women with non-cephalic
      presentation at term and no prior caesarean, referred to a specialist clinic.
      METHODS: Details of referrals, ECV attempts, and perinatal outcomes were
      prospectively collected and analysed. Multivariate binary logistic regression
      models were created to determine independent predictors of ECV success,
      reversion, and spontaneous version. MAIN OUTCOME MEASURES: External cephalic
      version success rates, predictors of success and cephalic presentation at birth,
      and perinatal outcomes. RESULTS: Three thousand eight had confirmed breech
      presentation; 2614 women underwent ECV. Ineligibility for ECV occurred in 117
      breech presentations (3.9%), and 297 eligible women (10.2%) declined it. ECV was
      successful in 1280 (49.0%, 95% CI 47.0-50.9%) (40% in nulliparous women; 64% in
      others); 1234 (97.3%) were cephalic at birth. Spontaneous version after failure
      occurred in 4.3% and was more common in multiparas (aOR 2.47, 95% CI 1.43-4.26)
      and those with a posterior fetal back (aOR 6.09, 95% CI 1.90-19.53). Reversion
      after successful ECV occurred in 2.2%. In women with a successful ECV whose fetus
      remained cephalic at birth, 85.7% delivered vaginally. The corrected perinatal
      mortality of the ECV cohort was 0.12%. CONCLUSION: External cephalic version has
      a low complication rate and is effective for most breech presentations, enabling
      vaginal birth and avoiding caesarean section. TWEETABLE ABSTRACT: External
      cephalic version can safely be performed with most breech presentations.

PMID- 30223310
TI  - Type IV allergy to antimalarials can mimic cutaneous manifestations of lupus
      erythematosus.

PMID- 30223311
TI  - The trouble with reporting and utilization of workplace violence data in health
      care.
AB  - AIM: The study aimed to evaluate the reporting, monitoring and use of workplace
      violence data in Victorian health services. BACKGROUND: Surveillance of workplace
      violence is important in understanding the circumstances in which workplace
      violence occurs and development of relevant and appropriate prevention and
      intervention strategies. METHOD: A descriptive exploratory approach was used.
      Fifteen staff from occupational health and safety, quality and safety, and nurse
      unit managers, from five major metropolitan health services were interviewed.
      Recorded interviews were transcribed verbatim and thematically analysed. RESULTS:
      Three themes were identified: (a) "under-reporting of workplace violence," (b)
      "inconsistent guidance" caused subjective and variable data coding and (c)
      "application of data" described how health services used the data available to
      them, to inform the development and implementation of systems designed to prevent
      workplace violence. CONCLUSIONS: Improved reporting systems may increase
      consistency in reporting, enable data sharing across organisations and assist in
      planning of prevention strategies. IMPLICATIONS FOR NURSING MANAGEMENT: Staff
      should be encouraged to complete incident reports for each episode of workplace
      violence. Incident reporting systems must be simplified to reduce the burden of
      reporting. Nurse managers should advocate for the sharing of health service
      workplace violence data, to enable improved prevention across all services.

PMID- 30223312
TI  - A gene cluster for fatty alcohol synthesis from a Reinekea-related bacterium that
      accumulates fatty alcohols.
AB  - This study reports on a marine bacterium that accumulates fatty alcohols
      (C14,16,18 ) at more than 1% (w/w) of the dry cell weight. This unique bacterium,
      designated as strain 1-4, is related to the genus Reinekea. A novel gene cluster
      for fatty alcohol synthesis, phsAB, is identified from strain 1-4. The phsA
      product shows significant homology to fatty acyl-CoA reductase (51% identity),
      whereas the phsB product shows very low homology to lipases. Interestingly, phsA
      alone causes Escherichia coli to accumulate fatty alcohols at 19% (w/w) of the
      dry cell weight. Moreover, the phsA-containing E. coli accumulate more fatty
      alcohols (24%) and grow faster after phsB is introduced, indicating that phsAB
      could greatly assist the mass production of fatty alcohols.

PMID- 30223313
TI  - Laser printing of microbial systems: effect of absorbing metal film.
AB  - Recently, it was shown that laser-induced forward transfer (LIFT) technology and
      the laser engineering of microbial systems (LEMS) technique (based on LIFT
      method) are effective for isolation of micro-organisms from different complex
      substrates. These techniques frequently utilize Au as an absorbing layer
      material. The purpose of this study was to investigate the influence of absorbing
      film materials (Au, Ti and Cr) on the effectiveness of laser printing of micro
      organisms to improve LEMS and LIFT techniques. It was shown that application of
      Ti and Cr absorbing layers activates bacterial growth after laser printing and is
      significantly more effective in comparison to Au films, which actually show a
      suppressing effect on bacterial cells. Results of this study can be applied for
      LEMS and LIFT protocols for improving bacterial isolation and microbial growth.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Laser-induced forward transfer technique
      (LIFT) is currently used for printing of micro-organisms and in biosensor
      techniques, for single-cell isolation, and for culturing of micro-organisms from
      complex substrates. We have studied the influence of absorbing film materials
      (Au, Ti and Cr) on the effectiveness laser printing of micro-organisms. It was
      shown that application of Ti and Cr absorbing layers activates bacterial growth
      and is more effective in LIFT compared to Au films, which actually have a
      suppressive effect on bacteria cells. The results can improve LIFT protocols for
      bacteria isolation and culturing of microbial systems.

PMID- 30223314
TI  - von Recklinghausen neurofibromatosis.

PMID- 30223315
TI  - Comparison of intraperitoneal versus intravenous dexamethasone on postoperative
      nausea and vomiting after gynecological laparoscopy: a randomized clinical trial.
AB  - Background: The aim of the study was to compare the effect of intraperitoneal
      versus intravenous dexamethasone for the reduction of postoperative nausea and
      vomiting (PONV) after gynecological laparoscopic surgeries. Methods: Eighty adult
      female patients, American Society of Anesthesiologists physical status I-II,
      scheduled for gynecological laparoscopic surgery were randomized to receive 8 mg
      dexamethasone intravenously (IV) (n = 40) or intraperitoneally (IP) (n = 40). The
      primary outcome was the incidence of PONV during the first 24 h following
      laparoscopy. Secondary outcomes included visual analogue scale (VAS) pain scores,
      total consumption of rescue analgesic during the first postoperative 24 h, the
      need for rescue antiemetic drugs and the incidence of pssible complications that
      may accompany medications. Results: Eleven women (27.5%) in the IV group had
      nausea versus only 3 (7.5%) women in the IP group during 24 h post laparoscopy (p
      = 0.03). However, 5 patients (12.5%) in the IV group experienced vomiting versus
      only 2 patients (5%) in the IP group (p = 0.42). No statistical differences in
      the severity of nausea or the need for rescue antiemetics between both groups. IP
      group had lower rate of side effects versus IV group (7.5% vs. 27.5%, p = 0.03).
      The most common side effects in the IV dexamethasone group were headache and
      dizziness. No significant differences between both groups in the mean VAS of pain
      and total meperidine consumption during the first 24 h postoperatively.
      Conclusions: Intraperitoneal dexamethasone in a dose of 8 mg at the end of
      gynecological laparoscopy reduces the incidence of postoperative nausea.

PMID- 30223316
TI  - Solubility, partitioning, oxidation and photodegradation of dichloroacetamide
      herbicide safeners, benoxacor and furilazole.
AB  - Approximately 242 million kg of herbicides are applied in the United States (US)
      annually. While herbicides prevent the growth of weeds, they can damage crops
      resulting in so called "herbicide injury." To increase herbicidal tolerance of
      crops, herbicide safeners are commonly added to formulations. Herbicidal safeners
      are labeled as inert ingredients in herbicide formulations and typically minimal
      fate and transport information is available. The objective of this study is to
      experimentally derive the aqueous solubility, octanol-water partition
      coefficient, and photo-degradation and permanganate oxidation of two
      dichloroacetamide safeners, benoxacor and furilazole. These results can be used
      to understand the environmental chemodynamics of these compounds and their
      degradation via common drinking water treatment systems containing permanganate.
      The aqueous solubility of benoxacor and furilazole was 22 and 235 mg L-1
      respectively while the estimated solubility from EPI Suite was 102.7 and 255 mg L
      1 respectively. The log octanol-water partition coefficient of benoxacor and
      furilazole was 2.23 and 1.96 respectively. The selected safeners were not
      photodegradable to any great extent. Both benoxacor and furilazole oxidation were
      found to be second order with respect to initial KMnO4 concentrations. The
      results of this study can be used to predict distribution of safeners after
      application in agricultural fields and aid in the design of treatment systems.

PMID- 30223317
TI  - Quantitative proteomic and transcriptional analyses reveal degradation pathway of
      gamma-hexachlorocyclohexane and the metabolic context in the actinobacterium
      Streptomyces sp. M7.
AB  - Highly contaminated gamma-hexachlorocyclohexane (lindane) areas were reported
      worldwide. Low aqueous solubility and high hydrophobicity make lindane
      particularly resistant to microbial degradation. Physiological and genetic
      Streptomyces features make this genus more appropriate for bioremediation
      compared with others. Complete degradation of lindane was only proposed in the
      genus Sphingobium although the metabolic context of the degradation was not
      considered. Streptomyces sp.M7 has demonstrated ability to remove lindane from
      culture media and soils. In this study, we used MS-based label-free quantitative
      proteomic, RT-qPCR and exhaustive bioinformatic analysis to understand lindane
      degradation and its metabolic context in Streptomyces sp. M7. We identified the
      proteins involved in the up-stream degradation pathway. In addition, results
      demonstrated that mineralization of lindane is feasible since proteins from an
      unusual down-stream degradation pathway were also identified. Degradative steps
      were supported by an active catabolism that supplied energy and reducing
      equivalents in the form of NADPH. To our knowledge, this is the first study in
      which degradation steps of an organochlorine compound and metabolic context are
      elucidate in a biotechnological genus as Streptomyces. These results serve as
      basement to study other degradative actinobacteria and to improve the degradation
      processes of Streptomyces sp. M7.

PMID- 30223318
TI  - Two-stage multi-fraction first-order kinetic modeling for soil Cd extraction by
      EDTA.
AB  - A two stage multi-fraction 1st-order kinetic model was established herein, which
      incorporates Cd species distribution in the contaminated site, chelate dosage and
      washing time, and two distinct extraction mechanisms are also emphasized there.
      The model was found to successfully simulate the experimental data of Cd
      extraction by EDTA; with the obtained parameters, we also got a similarly good
      agreement in other two Cd-contaminated soils. All normalized root-mean-square
      error, the index of agreement and modeling efficiency values showed that this
      model can be used to predict Cd kinetic extraction process in different types of
      soils with an excellent validity. Both simulated and experimental results
      indicate that a greater EDTA dosage reasonably leads to a higher Cd extraction
      efficiency and a faster extraction by the direct EDTA-complex. Different Cd
      species also show different extraction behavior. Part of Cd species associated
      with Fe/Mn hydro(oxides) (FeMnOx) become destabilized by slow EDTA-promoted
      dissolution but not yet detached, leading to an apparently high removal
      efficiency of Cd in FeMnOx fraction dependent on EDTA dosage. While the removal
      of exchangeable Cd and carbonates (EXCH+CARB) seemed unchanged with the EDTA
      dosage, due to the transformation of the undetached Cd in FeMnOx fractions.
      However, an extreme dosage (i.e. molar ratio of EDTA to metal equal to 20 herein)
      may accelerate the detachment of these destabilized Cd species, resulting in a
      substantially high extraction efficiency of EXCH+CARB fraction.

PMID- 30223319
TI  - In utero exposure to triphenyltin disrupts rat fetal testis development.
AB  - Triphenyltin is an organotin that is widely used as an anti-fouling agent and may
      have endocrine-disrupting effects. The objective of the current study was to
      investigate effects of triphenyltin on the development of rat fetal testis.
      Female pregnant Sprague Dawley dams were gavaged daily with triphenyltin (0, 0.5,
      1, and 2 mg/kg body weight/day) from gestational day 12 to day 21. Triphenyltin
      dose-dependently decreased serum testosterone levels (0.971 +/- 0.072 and 0.972
      +/- 0.231 ng/ml at 1 and 2 mg/kg, respectively) from control level (2.099 +/-
      0.351 ng/ml). Triphenyltin at 1 and 2 mg/kg doses also induced fetal Leydig cell
      aggregation, decreased fetal Leydig cell size and cytoplasmic size. Triphenyltin
      decreased the expression levels of Lhcgr, Scarb1, Star, Cyp11a1, Cyp17a1, Insl3,
      Fshr, Pdgfa, and Sox9 by 0.5 mg/kg dose and above. However, triphenyltin did not
      affect Leydig and Sertoli cell numbers. In conclusion, the current study
      indicated that in utero exposure of triphenyltin disrupted fetal Leydig and
      Sertoli cell development.

PMID- 30223321
TI  - The treatment of flowback water in a sequencing batch reactor with aerobic
      granular sludge: Performance and microbial community structure.
AB  - The extensive application of hydraulic fracturing technology has significantly
      promoted the large-scale development of shale gas. However, it is a great
      challenge for shale gas extraction to effectively manage large-volume flowback
      water (FW) with high salinity and complex organic substances. Here, we report an
      aerobic granular sludge (AGS) tolerable to high salinity, and suited to the
      treatment of FW. The performance of a sequencing batch reactor (SBR) with the AGS
      for the treatment of the synthetic FW and the microbial community structure at
      different salinity levels were investigated. The AGS fed with synthetic FW
      possessed a larger average particle size and a higher settling rate (50 m h-1).
      When NaCl concentration increased to 50.0 g L-1, the removal efficiency of total
      organic carbon (TOC) increased to 79 +/- 1%, and the removal rate of
      polyacrylamide (PAM) raised up to 42.7 +/- 0.7 g m-3 d-1. Alphaproteobacteria,
      Betaproteobacteria, Gammaproteobacteria, and Sphingobacteriia dominated in the
      microbial community of AGS. Cellvibrionaceae, Rhodocyclaceae, Enterobacteriaceae,
      Moraxellaceae, Pseudomonadaceae, and Halomonadaceae belonging to
      Betaproteobacteria and Gammaproteobacteria played important role in degrading
      PAM, polycyclic aromatic hydrocarbons (PAH), and some other organics in FW at
      high salinity. These results suggest that an AGS-based SBR is a promising
      technology for the treatment of FW.

PMID- 30223320
TI  - Enhanced removal of bio-refractory dissolved organic matter from cassava
      distillery wastewater by powdered activated carbon-ballasted coagulation:
      Detailed study of separation characteristics and mechanisms.
AB  - Efficient removal of bio-refractory dissolved organic matter (DOM) and colorants
      is essential for discharging or reusing the distillery wastewater. An important
      part of recalcitrant DOM still exists in the effluent of regular coagulation
      though the ferric coagulant has been found to be effective in decoloration. The
      present work adopted powdered activated carbon (PAC) as ballasting agent to
      achieve robust separation effect and efficiency of bio-refractory DOM from the
      bio-chemically treated cassava distillery wastewater (BTDWW). More than 90% of
      DOC could be removed at the PAC and Fe(III)-coagulant dosage of 1.40 g/L and 0.84
      g/L as Fe when the BTDWW was neutral. PAC should be dosed before coagulant in
      order to mix well with the DOM in the BTDWW. The analyses of DOM in effluent
      reveal that PAC facilitated the removal of lignin breakdown products which could
      not be well eliminated by regular coagulation; the removal of DOM with MW < 5 kDa
      was mostly enhanced. The characteristics of flocs demonstrate that PAC reinforced
      the interaction between Fe(III) species and DOM by providing more reaction sites.
      The sedimentation could be completed within the initial 5 min, and the highest
      settling velocity was almost 8 times higher than that of the only Fe(III)
      involved flocs. The large size and favorable robustness of PAC-involved flocs
      enabled decent sedimentation even though their stretched structure might not be
      desirable in regular coagulation. The PAC-ballasted coagulation is recommended as
      tertiary treatment of BTDWW considering its high efficiency and sound economic
      feasibility.

PMID- 30223322
TI  - Characterization and quantification of electron donating capacity and its
      structure dependence in biochar derived from three waste biomasses.
AB  - Biochar has shown a unique electrochemical property being involved in various
      redox reactions in soil and water. In this study, the electron donating
      capacities (EDCs) of biochar pyrolyzed at 200-800  degrees C from pine wood,
      barley grass and wheat straw were investigated by using the mediated
      electrochemical oxidation method. The EDC values for all biochar were in the
      range of 0.18-1.83 mmol e- (g biochar)-1, showing the increase as the temperature
      increased from 200  degrees C to 400  degrees C, the decrease from 400  degrees C
      to 650  degrees C, and then increase from 650  degrees C until to 800  degrees C.
      At low and intermediate temperatures of 200-650  degrees C, the EDCs were mainly
      attributed to the phenolic hydroxyl groups, while the conjugated pi-electron
      system associated with aromatic structure dominated the EDCs of biochar at the
      high temperatures of over 650  degrees C. The barley grass- and wheat straw
      derived biochar had higher EDCs than the pine wood-derived biochar, resulting
      from the higher phenolic hydroxyl groups in the former samples than the latter
      one. In conclusion, the reductive property of biochar was mainly attributed to
      both phenolic hydroxy group and conjugated pi-electron system associated with
      aromatic structure, depending on the pyrolytic temperature and feedstock source.
      The results will help us to obtain a complete view on the role of biochar in
      biogeochemical redox reactions and consider developing biochar with controlled
      redox properties for specific environmental applications such as electron shuttle
      and catalyst material.

PMID- 30223323
TI  - Application and mechanism of nucleation-induced pelleting coagulation (NPC) in
      treatment of fracturing wastewater with high concentration of dissolved organic
      matter.
AB  - To improve the separation efficiency of fluffy flocs during coagulation of
      fracturing wastewater with high concentration of dissolved organic matter, a
      novel nucleation-induced pelleting coagulation (NPC) process is proposed based on
      pelleting coagulation in this study. In the NPC process, nucleation agents were
      added to act as pellet seeds to generate high-density pellet flocs. The results
      implied that the necessary condition for the NPC process was to control the
      metastable state, i.e. zeta potential around -10 mV after addition of the
      coagulant, polyaluminium chloride (PAC). Diatomite, which was added after rapid
      mixing, was used as the nucleation agent, and its optimal dosage was about 100
      mg/L with particle size 100-200 MUm. In addition, the dosage of the coagulant
      aid, polyacrylamide (PAM), significantly affected the performance of the NPC
      process, and the optimal PAM dosage was 10 mg/L in this study. It was found that
      60 rpm (G = 55.1 s-1) was the optimal hydraulic condition for pellet growth
      during slow mixing. The pellet floc settling velocity reached 14.9 mm/s and the
      particle size (d50) reached 4.6 mm with an effective density of 0.021 g/cm3 at
      the optimal condition, which was one order higher than that of conventional
      aluminium flocs.

PMID- 30223324
TI  - Removal of N-nitrosodimethylamine precursors by cation exchange resin: The
      effects of pH and calcium.
AB  - Cation exchange resins have proved to be efficient in removing precursors of N
      nitrosodimethylamine (NDMA). NDMA is a probable human carcinogen with a
      calculated lifetime cancer risk of 10-6 at 0.7 ng/L in drinking water. This paper
      investigated the effect of pH and calcium levels on the removal of NDMA
      precursors using a cation exchange resin. At pH 5 and 7, 30-50% of NDMA
      precursors, measured by formation potentials (FPs) changes before and after the
      treatment, were removed by Plus resin. However, increases in NDMA FPs were
      observed after the treatment at pH 10 indicating that NDMA precursors were
      released from the resin. NDMA FPs removals in samples containing 15 and 115 mg/L
      Ca2+ were 40% and -10% after the ion exchange treatments at pH 7, respectively.
      It was found that in the presence of high concentration of calcium only one out
      of four cation exchange resins released NDMA precursors (probably due to
      manufacturing impurities). Also, the release of NDMA precursors depended on the
      calcium concentration and the contact time of the resin with the solution
      containing calcium. Nonetheless, NDMA precursors release from the resin subsided
      significantly with increasing the number of regeneration cycles of the resin.

PMID- 30223325
TI  - Growth suppression and apoptosis-like cell death in Microcystis aeruginosa by
      H2O2: A new insight into extracellular and intracellular damage pathways.
AB  - H2O2 has been suggested and applied as effective algaecide for harmful
      cyanobacterial bloom control, however, the transport of exogenous H2O2 into
      microalgal cells, the subsequent intracellular damage pathway and dose-response
      variations were little studied. We addressed these questions in a bloom-forming
      cyanobacterium Microcystis aeruginosa with H2O2 at 0.1-1.5 mM. The results showed
      that H2O2 at 0.4 mM and above significantly suppressed M. aeruginosa growth for
      over two weeks, and induced apoptosis-like death in terms of membrane potential
      dissipation, caspase-3 activation, chromatin condensation, and lysis induction.
      However, the dose-response effects were not monotonic. H2O2 at 0.7 mM resulted in
      the severest growth suppression among 0.1-1.5 mM treatments, including the lowest
      biomass for 74% loss, the highest cell lysis ratio for 79%, and the highest
      utilization rate of H2O2 for 0.101 mM d-1. Moreover, several evidence point to
      severer apoptosis-like cell death in 0.7 mM treatments, involving fastest and
      severest cell lysis, smallest cell size and wrinkled surface and lowest membrane
      potential. Therefore, the apoptosis-like cell death induced by H2O2 at moderate
      dosages should be a crucial cause for the non-monotonic dose-response effects on
      growth suppression. Additionally, intracellular H2O2 level increased rapidly
      within 20 min after exposure at 0.4 mM and above, directly confirming the
      transport of exogenous H2O2 into M. aeruginosa cells and the intracellular
      damages due to subsequent elevation in intracellular oxidative stress. The study
      demonstrates that H2O2 at moderate dosages could be a promising method for the
      biomass control, in a fast and efficient way, on M. aeruginosa blooms.

PMID- 30223326
TI  - The prediction of mercury bioavailability for common carp (Cyprinus carpio L.)
      using the DGT technique in the presence of chloride ions and humic acid.
AB  - The ability of the DGT technique to predict Hg2+ bioavailability for input
      tissues (skin, gills, and scales) of common carp in the presence of chloride ions
      and humic acid (HA) was evaluated. The mercury accumulation by the DGT units and
      input tissues of carp decreased with an increasing concentration of chloride ions
      (29-180 mg L-1) and HA (0-5 mg L-1). In the presence of chloride ions and HA,
      statistically significant correlations (Pearson's correlation coefficients 0.731
      0.954) were determined between the rate of mercury accumulation by input tissues
      of carp and the rate of mercury accumulation by the DGT units. The laboratory
      experiments suggest the possibility of using the DGT technique for predicting the
      mercury bioaccumulation in natural aquatic ecosystems instead of commonly used
      input tissues of fish.

PMID- 30223327
TI  - Assessment of trace metal contamination of wetland sediments from eastern and
      western coastal region of India dominated with mangrove forest.
AB  - Ecosystem and biodiversity of India's coastal areas dominated with mangrove
      forest have been threatened by growing anthropogenic activities. The present work
      aims to investigate the contamination of wetland sediments with trace elements
      and assess the sediment quality at different sampling locations in eastern and
      western costal region dominated with mangrove forest. The longitudinal profile of
      trace elements in sediments from different sampling locations analyzed by
      employing Energy Dispersive X-ray Fluorescence (EDXRF) spectrometer shows
      variations in distribution of elements like Al, Si, K, Ca, V, Cr, Mn, Fe, Ni, Cu,
      Zn and Pb. The enrichment factor (EF) and Geo-accumulation index (Igeo) values
      suggested depletion of clay minerals and enrichment of heavy metals like Cr, Cu
      Fe and Mn. Depending on the variations in Igeo values, the elements are put into
      Igeo Class 0 to 3 levels of contamination. Contamination factor (Cf) and
      pollution load index (PLI) suggested deterioration of sediments analyzed in the
      present study. Assessment of ecological risk potential of elements suggests that
      few elements (Cr and Cu) are moderately contaminated and may cause environmental
      stress on the exposed flora and fauna.

PMID- 30223328
TI  - Seasonal variation of potential denitrification rate and enhanced denitrification
      performance via water-lifting aeration technology in a stratified reservoir-A
      case study of Zhoucun reservoir.
AB  - Zhoucun reservoir is one of the major water resources in Zao Zhuang city,
      northern China. The seasonal distribution of surface sediment denitrification
      rate and enhanced performance of denitrification via water-lifting aeration
      technology were explored using the acetylene-inhibition technique. Surface
      sediment denitrification rates ranged from 2.57 +/- 1.32 to 923.90 +/- 86.81 nmol
      N2/(g dw.h), with the highest rates in November (ANOVA, p < 0.05) and
      significantly low rates in June, July, and August (ANOVA, p < 0.05), mainly
      because of the seasonal differences in nitrate concentration, water temperature,
      and sediment total nitrogen (STN). Meanwhile, the N2/(N2+N2O) ratio (83.44-91.70%
      for the highest sediment denitrification period) indicated that N2 accounted for
      a majority of denitrification. Correlation analysis between various environmental
      factors and denitrification was conducted, and nitrate concentration, STN, low
      molecular weight organic carbon, the number of aerobic denitrifying bacteria, and
      the environmental parameters of oxidation-reduction potential (ORP), pH,
      electrical conductivity (EC), and chlorophyll a (Chl-a) presented significant
      relationships during the entire study period. On the basis of the multiple
      regression model, nitrate and low molecular weight organic carbon concentration
      were the most influential factors on denitrification variability. Moreover, the
      denitrification rates of the surface sediment clearly increased, from 5.28 to
      13.22 nmol N2/(g dw.h) to 1117.02-3129.47 nmol N2/(g dw.h), which were higher
      than those in the non-operating year. This suggests that the denitrification in
      the sediment system could be enhanced in situ by water-lifting and aeration
      technology in the reservoir ecosystem.

PMID- 30223329
TI  - Single and combined exposure of microcystin-LR and nitrite results in
      reproductive endocrine disruption via hypothalamic-pituitary-gonadal-liver axis.
AB  - Microcystin-LR (MC-LR) released by Microcystis blooms degradation usually co
      exists with a chemical called nitrite, posing a serious harm to aquatic
      organisms. To assess the single and combined effects of MC-LR and nitrite on the
      reproductive endocrine system, a fully factorial experiment was designed and
      adult male zebrafish (Danio rerio) were exposed to 9 treatment combinations of MC
      LR (0, 3, 30 MUg/L) and nitrite (0, 2, 20 mg/L) for 30 d. The results showed that
      both MC-LR and nitrite caused concentration-dependent effects including the
      growth inhibition, decreased gonad index as well as testicular injuries with
      widen intercellular spaces and seminiferous epithelium deteriorations. And
      testicular pathological changes in the co-exposure groups of MC-LR and nitrite
      were similar but more serious than those in single-factor exposure groups.
      Concurrently, exposure to MC-LR or nitrite alone could significantly decrease T
      levels by downregulating gene expressions (gnrh2, lhbeta, ar, lhr) in the
      hypothalamic-pituitary-gonadal-liver-axis (HPGL-axis), and there were significant
      interactions between MC-LR and nitrite on them. In contrast, E2 levels as well as
      transcriptional levels of cyp19a1b, cyp19a1a and vtg1 showed significant
      inductions with increasing MC-LR concentrations, indicating an estrogen-like
      effect of MC-LR. Our findings illustrated that co-exposure of MC-LR and nitrite
      synergistically cause reproductive dysfunction by interfering with the HPGL axis
      in male fish, which prompt us to focus more on the potential risks in fish
      reproduction and even population dynamics due to the wide occurrence of toxic
      cyanobacterial blooms.

PMID- 30223330
TI  - Rapid and complete dehalogenation of halonitromethanes in simulated
      gastrointestinal tract and its influence on toxicity.
AB  - Halonitromethanes (HNMs) as one typical class of nitrogenous disinfection
      byproducts in drinking water and wastewater are receiving attentions due to their
      high toxicity. This study applied a simulator of the human gastrointestinal tract
      to determine the dehalogenation processes of trichloronitromethane,
      bromonitromethane and bromochloronitromethane for the first time. Influence of
      digestion process of HNMs on gut microbiota and hepatotoxicity was further
      analyzed. Results showed that the three HNMs were rapidly and completely
      dehalogenated in the gastrointestinal tract, especially in the stomach (2 h
      retention Time) and small intestine (4 h retention Time). Mucin, cysteine,
      pancreatin and bile salts in the digestive juice played major roles in the
      dehalogenation process. HNMs and their dehalogenation products in the resulting
      fluids of stomach induced the highest toxicity followed by those in intestine and
      colon, exhibiting dose-dependent effects. Although most HNMs were degraded in the
      stomach and small intestine, residual HNMs entered into colon changed the
      microbial community. Abundance of several genera, such as Bacteroides,
      Lachnospiraceae_unassigned and Lactobacillus had high correlation with exposure
      concentration of HNMs. This study sheds new light on dehalogenation and toxic
      processes of HNMs by oral exposure, which provides basic data for their human
      health risk assessment.

PMID- 30223331
TI  - Co-expression of YieF and PhoN in Deinococcus radiodurans R1 improves uranium
      bioprecipitation by reducing chromium interference.
AB  - Overexpression of the enzyme phosphatase (PhoN/PhoK) in the radiation-resistant
      bacterium Deinococcus radiodurans could be an efficient strategy for uranium
      remediation. However, the presence of other metals in nuclear wastes often
      interferes with uranium bioprecipitation. In our study, the uranium-precipitating
      ability of the PhoN-expressing D. radiodurans strain (Deino-phoN) significantly
      decreased by 45.4% in 13 h in the presence of chromium (VI); however, it was
      partially recovered after supplementation with chromium (III). Therefore, the
      reduction of chromium (VI) to chromium (III) was obtained by the co-expression of
      the YieF protein and PhoN in D. radiodurans (Deino-phoN-yieF). As a result, an
      increase in the chromium (VI) reduction (25.1%) rate was observed in 24 h.
      Furthermore, uranium precipitation also increased by 28.0%. For the
      decontamination of groundwater, we immobilized Deino-phoN-yieF cells using
      Polyvinyl alcohol (PVA)-sodium alginate (SA) beads, followed by incubation in a
      bioreactor. Approximately 99% of chromium (VI) and uranium (VI) was removed after
      4 continuous cycles operated for a period of over 20 days at room temperature (25
      degrees C). Therefore, Deino-phoN-yieF could be used as a potential biological
      agent for mixed radioactive nuclear waste remediation.

PMID- 30223332
TI  - Degradation of geosmin and 2-methylisoborneol in water with UV/chlorine:
      Influencing factors, reactive species, and possible pathways.
AB  - Geosmin (GSM) and 2-methylisoborneol (2-MIB) are two common odor compounds in
      drinking water. In this paper, the performance of UV/chlorine was compared with
      that of chlorine and UV to degrade GSM (100 ng L-1) and 2-MIB (100 ng L-1) in
      water. UV/chlorine was further exploited, and a steady-state kinetic model was
      used to conduct a detailed study on efficiency, rate, reactive species and
      pathway. The results showed that UV/chlorine greatly could improve the removal
      ratio to 90% within 5 min, from approximately 20% with only UV or dark chlorine
      in 60 min. The removal ratio and rate depended on UV light intensity, free
      chlorine dosage, reaction time and water quality parameters (e.g. pH,
      concentrations of HCO3- and Cl-). Among these factors, the first two obviously
      could accelerate the rate and increase the ratio. The degradation was also
      significantly improved in an acidic condition, while alkaline conditions and HCO3
      had inhibitory effects, and Cl- created no difference. Contributions of OH and
      Cl to the degradation of 2-MIB and GSM were further revealed, and OH was found to
      be the most important reactive species. In the UV/chlorine process, 6 degradation
      byproducts of 2-MIB, including 1 alcohol, 2 ketones, and 3 olefins, were
      identified, and 14 degradation byproducts of GSM, including 6 ketones, 1
      aldehyde, 2 alcohols, 3 naphthenes, and 2 olefins, were found by using solid
      phase microextraction coupled to gas chromatography-mass spectrometry. The
      possible degradation pathways of GSM and 2-MIB in UV/chlorine thus were proposed.

PMID- 30223333
TI  - Triphenyltin exposition induces spermatic parameter alters of Calomys laucha
      species.
AB  - The present study aims to evaluate the influence of triphenyltin (TPT) exposure
      on reproductive physiology on Calomys laucha species, since this species inhabits
      regions susceptible to exposure to this contaminant. Animals exposed to the
      highest dose (10.0 mg/kg) presented signs of severe intoxication in only 7 days
      of exposure, demonstrating a higher sensitivity of this species to triphenyltin.
      The 10.0 mg TPT/kg dose was analyzed separately for short-term exposure and
      results suggest that exposure to this dose was severely detrimental to sperm
      activity. Among the main results obtained in the evaluation of sperm kinetics, a
      reduction in total motility was observed from the 0.5 mg TPT/kg group,
      accentuated according to the increase in the doses of TPT. In progressive
      motility, there was a decrease from the dose of 0.5 mg TPT/kg and maintained the
      plateau until the dose of 5.0 mg TPT/kg. It was also observed an increase in the
      distances and velocities average path, rectilinear and curvilinear in doses of
      2.5 and 5.0 mg/kg. From the flow cytometry, evaluation a decrease in
      mitochondrial functionality was observed as the dose increased. Increased
      membrane fluidity was also observed from the 5.0 mg TPT/kg dose and the acrosome
      reaction presented higher values at doses of 0.5 and 5.0 mg TPT/kg. We can
      conclude that TPT causes impairment of the sperm activity, reducing it in
      individuals exposed in the adult phase.

PMID- 30223334
TI  - Sorption and desorption characteristics of anionic surfactants to soil sediments.
AB  - Surfactants are important environmental chemicals due to their extensive domestic
      and industrial applications, such as subsurface organic pollution remediation and
      enhanced oil recovery. However, the interaction of surfactants with subsurface
      material particularly the desorption behavior of surfactants is less understood.
      Surfactant desorption is essential to control the fate and transport of
      surfactants as well as organic pollutants. In this study, the sorption and
      desorption of linear sodium dodecylbenzene sulfonate (SDBS) and sodium hexadecyl
      diphenyl oxide disulfonate (DPDS) with two types of soil sediment samples are
      compared. Sorption of surfactants can be modeled by hydrophobic sorption. Less
      DPDS sorption is observed at a higher aqueous concentration, which is attributed
      to the competition between surfactant micelles and sediment organic matter for
      DPDS sorption. A significant fraction of the sorbed surfactants resists
      desorption, and this is not a result of surfactant precipitation or desorption
      kinetics. Surfactant desorption behavior is similar to the irreversible
      desorption of hydrocarbons from soil with only half of the resistant phase
      surfactant being readily extracted by heated solvent extraction. The
      sorption/desorption data are interpreted with a molecular topology and
      irreversible sorption model. The knowledge of this study can be useful in
      understanding the environmental fate and transport of these common anionic
      surfactants. The methodology developed in this study can be expanded to study the
      sorptive nature of a wider range of surfactants in the environment.

PMID- 30223335
TI  - New brominated flame retardants and dechlorane plus in the Arctic: Local sources
      and bioaccumulation potential in marine benthos.
AB  - The aim of the present study was to investigate the presence and bioaccumulation
      of new flame retardants (nBFRs), polybrominated diphenyl ethers (PBDEs) and
      dechlorane plus (DDC-CO) in the marine environment close to an Arctic community.
      Passive sampling of air and water and grab sampling of sediment and amphipods was
      used to obtain samples to study long-range transport versus local contributions
      for regulated and emerging flame retardants in Longyearbyen, Svalbard. BDE-47 and
      -99, alpha- and beta-tetrabromoethylcyclohexane (DBE-DBCH), syn- and anti
      dechlorane plus (DDC-CO) were detected in all investigated matrices and the DDC
      COss at higher concentrations in the air than reported from other remote Arctic
      areas. Water concentrations of SigmaDDC-COSs were low (3 pg/L) and comparable to
      recent Arctic studies. SigmanBFR was 37 pg/L in the water samples while SigmaPBDE
      was 3 pg/L. In biota, SigmaDDC-COSs dominated (218 pg/g ww) followed by SigmanBFR
      (95 pg/g ww) and SigmaPBDEs (45 pg/g ww). When compared with other areas and
      their relative distribution patterns, contributions from local sources of the
      analysed compounds cannot be ruled out. This should be taken into account when
      assessing long-range transport of nBFRs and DDC-COs to the Arctic. High
      concentrations of PBDEs in the sediment indicate that they might originate from a
      small, local source, while the results for some of the more volatile compounds
      such as hexabromobenzene (HBBz) suggest long-range transport to be more important
      than local sources. We recommend that local sources of flame retardants in remote
      areas receive more attention in the future.

PMID- 30223336
TI  - Occurrence and spatial distribution of perfluorinated compounds in groundwater
      receiving reclaimed water through river bank infiltration.
AB  - Perfluorinated compounds (PFCs) in groundwater are of widespread concern due to
      their potential toxicity to human health and ecological systems. PFCs in rivers
      can infiltrate into groundwater through riverbank infiltration, potentially
      endangering the safety of drinking water and causing a deterioration in the
      groundwater environment. This study investigated the occurrence of PFCs in rivers
      and riverside groundwater from 2014 to 2017 in a city in north China. PFCs were
      detected in most of the groundwater samples, ranging from not detected to 64.8 ng
      L-1. The predominant PFCs in both river and groundwater samples were
      perfluorooctane sulfonate, perfluorooctanoic acid, perfluorobutane sulfonate and
      perfluorobutanoic acid. The PFC concentrations and major compounds were
      consistent in both the river and riverside groundwater samples at each site,
      suggesting that the adjacent river was the source of the PFCs in the riverside
      groundwater. The spatial distribution of the PFCs in the riverside groundwater
      was affected by the hydraulic connection between the groundwater and the river,
      the lithology of the aquifer and the properties of the compounds. The results
      indicated that PFCs were attenuated during riverbank infiltration and the ability
      of different riverbank lithologies to remove PFCs was in the order sandy clay >
      fine sand > sandy gravel. Perfluorooctane sulfonate concentrations decreased
      sharply with increasing distances from river, whereas perfluorooctanoic acid,
      perfluorobutane sulfonate and perfluorobutanoic acid could by transported for
      greater distances in riverside groundwater. This study provides valuable
      information on PFCs in riverside groundwater affected by riverbank infiltration.

PMID- 30223337
TI  - Distributions of diluted bitumen and conventional crude oil in a range of water
      types.
AB  - Concern about the impacts that accidental discharge of under-investigated, heavy
      petroleum products may have on aquatic environments has prompted a comparative
      examination of the behaviours of diluted bitumen (DB) and light conventional
      crude (CC) oil in different water types. Distributions of oil among the water
      column and floating water-in-oil (w/o) emulsion are evaluated by a novel,
      reproducible procedure involving mixing oil with water, then separating,
      extracting, and quantifying the total absolute oil content of the water column
      via gravimetric and gas-chromatographic (high-temperature simulated distillation)
      analyses. The CC contents of water columns tend to be significantly greater than
      those of DB under comparable conditions, while the fraction of oil remaining
      afloat at the water's surface is greater for DB than for CC. The elucidated phase
      distribution patterns have important implications pertaining to the
      recoverability of these oils in the event of their release into aquatic
      environments, which serves to inform best practices for oil spill response. For
      both DB and CC, oil contents within water columns are the highest in waters of
      low salinity and high pH. Water contents of buoyant w/DB emulsions are
      significantly greater than those of w/CC emulsions after 60 min at rest, and are
      the highest in waters of low salinity and low pH. The effect of crude oil on the
      pH of water is also studied, and DB is found to have a greater effect than CC on
      water samples of varying initial pH.

PMID- 30223338
TI  - Cultivation and stable operation of aerobic granular sludge at low temperature by
      sieving out the batt-like sludge.
AB  - Aerobic granules were successfully cultivated at 10  degrees C with relatively
      low strength substrate. Stable granules coexisted with the batt-like sludge (BLS)
      were obtained in 60 days. After removing the BLS, nutrient removal performance
      was greatly improved and stable removal efficiencies of 99% phosphorous, 98%
      ammonia and 60% TN were achieved. The bacterial community structure revealed that
      it was an unclassified-Comamonadaceae genus dominant in the BLS, which
      represented for low relative abundance in mature granules. Overgrowth of
      unclassified-Comamonadaceae genus was considered to be the key factor for
      inhibiting the performance of granules. The final configuration of granules was
      dominated by DPAO genus Flavobacterium and polysaccharide nutritional genus
      Chryseolinea. This study showed that stable aerobic granules with superior
      performance under low temperature could be successfully cultivated by sieving out
      the BLS.

PMID- 30223339
TI  - Polychlorinated naphthalene concentrations and distribution in feed raw
      materials.
AB  - Concentrations and patterns of 75 PCN congeners in feed raw materials of animal
      and plant origin were investigated. Six types of feed raw materials of animal
      origin and three types of feed raw materials of plant origin from China were
      collected in 2016. The total concentrations of PCNs in the collected materials
      ranged from 147 to 1009 ng kg-1, with the highest occurring in fish meal. The
      mean PCNs concentration in feed raw materials of animal origin (551 ng kg-1) was
      higher than in those of plant origin (294 ng kg-1). Additionally, lower
      chlorinated PCNs were the main homologues in raw feed materials, while Di-CNs
      were the predominant homologues in all samples (mean: 53%), followed by tri-CNs
      (mean: 28%). The most abundant congeners were CN5/7 and 24/14. Additionally, the
      toxicity equivalencies (TEQs) of PCNs in the feed raw materials ranged from 0.010
      to 0.046 ng TEQ kg-1, with the highest TEQ concentrations of PCNs detected in
      gluten meal. Together, CN5/7, 66/67, 65/70, and 73 contributed approximately 64%
      of the total PCN TEQs in raw feed materials. Concentrations of polychlorinated
      dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and
      polychlorinated biphenyls (PCBs) in the feed raw materials were detected to
      compare the TEQ distribution of those dioxin-like compounds. The mass
      concentrations of PCNs were 1-3 orders of magnitude higher than those of PCDD,
      PCDFs and PCBs, while the TEQ concentrations of PCNs contributed 2.0%-6.5% of the
      total TEQs of PCNs, PCDDs, PCDFs and PCBs in the feed raw materials.

PMID- 30223340
TI  - Photodegradation of brominated flame retardants in polystyrene: Quantum yields,
      products and influencing factors.
AB  - Brominated flame retardants (BFRs) are widely used as additives in plastics,
      textiles and electronics materials. Here, we investigated the photodegradation of
      four BFRs including decabromobiphenylether (BDE-209), tetrabromobipsphenol A
      (TBBPA), tetrabromobisphenol A-bis(2,3-dibromopropylether) (TBBPA-DBPE) and
      tetrabromobisphenol A bis (allyl) ether (TBBPA-BAE). Experiments were carried out
      in polystyrene (PS) films using monochromatic and polychromatic irradiations. For
      comparison, irradiations were also carried in a solvent (tetrahydrofuran: THF).
      Monitoring of BFR degradation was performed using bulk and surface infrared (IR)
      measurements, as well as by extraction and HPLC-UV. Photoproducts were
      characterized using HPLC-high resolution electrospray ionization mass
      spectrometry (HPLC-ESI-Orbitrap-MS). All four BFRs underwent photochemical
      transformation in THF at 290 nm with a quantum yield (Phi) ranging from 0.05 for
      TBBPA to 0.27 for BDE-209, indicating an increase of photoreactivity with the
      number of Br atoms in BFRs. On the other hand, no major difference in the Phi
      values was observed when BFRs were embedded in PS films (Phi: 0.82-0.89). The
      higher photoreactivity in PS appears to be associated with a fast oxidation of PS
      as revealed by infrared (IR) analysis and yellowing of the films. Interestingly,
      the faster the yellowing occurred, the faster the BFR degradation was inhibited
      due to light screening effect. Several major photoproducts were identified for
      TBBPA and TBBPA-DBPE. Additional photoproducts possibly arising from PS oxidation
      and bromination by Br? were observed for the first time. This work provides a
      better understanding of the reactivity and fate of BFRs in polymers allowing for
      a better assessment of their environmental impacts.

PMID- 30223341
TI  - "Rebound" hypercoagulability after interruption of anticoagulation in patients
      with atrial fibrillation.

PMID- 30223342
TI  - Atrial fibrillation and sleep apnea: A chicken and egg situation.

PMID- 30223343
TI  - The new evidence on cryoballoon ablation to persistent atrial fibrillation.

PMID- 30223344
TI  - Reply: The emergence of clarifying the role of gut microbes in arrhythmia.

PMID- 30223345
TI  - New risk stratification on SCN5A mutation in Brugada syndrome.

PMID- 30223346
TI  - Response to letter from Drs. Li et al. regarding our paper in Int. J. Cardiol.
      2018. Doi: 10.1016/j.ijcard.2017.09.010: SCN5A mutation type and topology are
      associated with the risk of ventricular arrhythmia by sodium channel blockers.

PMID- 30223347
TI  - Heart failure and sleep related breathing disorders: Data from PROMISES (Progetto
      Multicentrico Italiano Sonno e Scompenso Cardiaco) study.
AB  - BACKGROUND: In heart failure (HF) sleep problems and sleep-related breathing
      disorders are frequently reported and are associated with poor prognosis.
      However, only few large clinical studies have investigated this issue in heart
      failure through breathing pattern analysis by polysomnography. METHODS AND
      RESULTS: 370 HF patients, with either moderate-severe reduced ejection fraction
      or with clinical decompensation, consecutively referred to 10 participating
      cardiology centers, have been enrolled in the PROMISES Study, an Italian project
      aimed at generating a large, multidisciplinary database of anthropometric,
      clinical, echocardiographic and sleep data, the last derived from overnight
      unattended cardio-respiratory polysomnography in HF patients. Obstructive sleep
      apnea was the most frequent form of sleep related breathing disorders observed in
      our cohort (35.4% with an AHI cutoff of 15). The possible determinants of sleep
      related breathing disorders were analyzed through stepwise logistic regression
      analysis and two multivariate models showing that a markedly reduced left
      ventricular ejection fraction was the most important factor associated with
      central sleep apneas (OR = 7.7 for AHI cutoff = 15 and LVEF <= 35%) together with
      male gender and increasing age. Conventional risk factors for obstructive sleep
      apnea did not identify HF patients affected by this condition. Conversely, a
      greater neck circumference was associated with an increased risk for central
      apneas. CONCLUSIONS: Our paper offers a deeper insight into the features of SRBD
      and its determinants in HF patients, leading in turn to a better clinical
      management of these comorbid patients.

PMID- 30223348
TI  - Secular trends in first-time hospitalization for heart failure with following one
      year readmission and mortality rates in the 3.8 million adult population of
      Silesia, Poland between 2010 and 2016. The SILCARD database.
AB  - BACKGROUND: Heart failure (HF) continues to be an important medical and social
      problem, with high morbidity and mortality. Data on the trends in
      hospitalizations, hospital readmissions and mortality is of great importance both
      from the epidemiological and clinical points of view. METHODS AND RESULTS: We
      analyzed the secular trends in first-time hospital admissions for heart failure
      between 2010 and 2016, derived from SILCARD database, covering a population of
      3.8 million adults. Patient characteristics as well as data on in-hospital and 12
      month outcomes were recorded for each year. The total number of first-time
      hospitalizations for HF as the primary diagnosis showed a downward trend during
      the study period (reduction by 12%, p = 0.07), with a constant patient age (mean
      74.3 +/- 11.3 years). The length of hospital stay shortened from 10.9 to 9.6 days
      (p = 0.003). Crude in-hospital mortality remained constant at around 14% (p =
      0.55), but after adjustment for sex and age, mortality rates tended to decrease
      from 17.2% in 2010 to 11.5% in 2016 (p = 0.007). All-cause hospital readmission
      rates in 12-month follow-up increased which was due to non-CV hospitalizations,
      since both CV- and HF-related readmissions were constant throughout the years.
      Crude 12-month mortality was constant, but after adjustment for age and sex
      absolute reduction by about 10% was found (p = 0.02). CONCLUSIONS: Despite the
      decreasing duration of hospital stay, significant improvement in both in-hospital
      and long-term survival was observed, with constant rates of hospital readmissions
      related to HF.

PMID- 30223349
TI  - Therapies for cardiac light chain amyloidosis: An update.
AB  - Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis,
      affecting around 10 people per million per year. This serious disorder is
      characterized by the presence of a clone of bone marrow plasma cells that
      produces monoclonal light chains (LCs) of the kappa or predominantly lambda type.
      These amyloidogenic LCs undergo extracellular misfolding and aggregation into
      proteotoxic soluble oligomers and amyloid fibrils that deposit within tissues.
      The lethal consequences of AL amyloidosis are due to the toxic products (the LCs)
      and not to the malignant behaviour of the plasma cell clone. Almost 80% of
      patients with AL amyloidosis have some degree of cardiac involvement, manifesting
      as heart failure (HF), and carrying a particularly poor prognosis. The past
      decade has seen major advances in the treatment of AL amyloidosis, and a rapidly
      fatal disease has become a treatable and possibly curable condition. The number
      of therapeutic options is rapidly expanding, offering hope to address currently
      unmet needs (most notably, the treatment of frail patients). The treatment of AL
      amyloidosis consists in a combination of agents targeting multiple steps of the
      amyloid cascade, associated with effective HF management, and there is ground for
      hope for dramatically improving the outcome in the near future. In the present
      review we will summarize our current knowledge on therapy for cardiac AL
      amyloidosis, targeting clinical cardiologists involved in the care of this
      serious disorder.

PMID- 30223350
TI  - Heart rate, pulse pressure and mortality in patients with myocardial infarction
      complicated by heart failure.
AB  - OBJECTIVE: To assess the relationship between heart rate (HR), pulse pressure
      (PP), and their association with mortality in a population of high-risk patients
      following acute myocardial infarction (MI). METHODS: We performed an analysis in
      22,398 patients included in "The High-Risk Myocardial Infarction Database
      Initiative", a database of clinical trials evaluating pharmacologic interventions
      in patients with MI complicated by signs of heart failure (HF) or left
      ventricular dysfunction. We found an interaction between HR and PP. Based on
      median HR and median PP, patients were divided in four categories: (1) HR < 75
      bpm and PP >= 50 mm Hg (reference), (2) HR < 75 bpm and PP < 50 mm Hg, (3) HR >=
      75 bpm and PP >= 50 mm Hg, and (4) HR >= 75 bpm and PP < 50 mm Hg. The
      association between these categories and outcomes was studied using a Cox
      proportional hazard model. RESULTS: After a median follow-up of 24 (18-33)
      months, 3561 (16%) patients died of all-causes and 3048 (14%) patients of
      cardiovascular (CV) causes. In multivariate analysis, patients from the fourth
      category had the highest risk of all-cause mortality (hazard ratio of 1.69; 95%
      CI: 1.53-1.86) and CV mortality (hazard ratio of 1.78; 95% CI: 1.60-1.97).
      CONCLUSIONS: There is an interaction between HR and PP in patients with HF
      following MI, with the highest risk being conferred by a clinical status with
      both an elevated HR and a lower PP. These findings identify a high-risk
      population likely to require an aggressive diagnostic and management strategy.

PMID- 30223351
TI  - Facts and details: Ivabradine in acute decompensated heart failure.

PMID- 30223352
TI  - LncRNA H19 regulates cardiomyocyte apoptosis and acute myocardial infarction by
      targeting miR-29b.

PMID- 30223353
TI  - Comment on the original paper entitled "Neural cell adhesion molecule-1 may be a
      new biomarker of coronary artery disease".

PMID- 30223354
TI  - A novel glucose-Pin1-eNOS-NO signaling axis links diabetes mellitus with
      cardiovascular diseases.

PMID- 30223355
TI  - Initial orthostatic hypotension among patients with unexplained syncope: An
      overlooked diagnosis?
AB  - BACKGROUND: Initial orthostatic hypotension (IOH) is a clinical syndrome of
      transient orthostatic hypotension that is defined as a drop in blood pressure of
      >40 mm Hg systolic and/or >20 mm Hg diastolic within 15 s after standing,
      accompanied by symptoms of cerebral hypoperfusion, but without sustained
      orthostatic hypotension (blood pressure decrease >20/10 mm Hg after 1-3 min of
      standing). As the etiology of syncope remains unknown in a large proportion of
      patients, we hypothesized that IOH is highly prevalent among patients with
      unexplained syncope. METHODS: We studied 250 consecutive outpatients with
      unexplained syncope that were evaluated in the syncope-unit of our tertiary
      referral hospital. We measured hemodynamic changes in response to active standing
      using a beat-to-beat blood pressure measurement device, first after lying supine
      for >5 min and then after squatting for 30 s. RESULTS: 11.2% of the patients were
      diagnosed with syncope due to IOH, with a mean fall in blood pressure of 47.4 +/-
      12.5/29.0 +/- 10.7 mm Hg within 15 s after standing up. Therefore, IOH was the
      second commonest cause of syncope in our cohort. 46.2% of the patients diagnosed
      with syncope due to IOH used antihypertensive drugs, mostly betablockers (41.6%)
      and/or tamsulosin (24.9%). The squatting-to-standing-test in addition to the
      lying-to-standing-test resulted in only 3 additional patients diagnosed with
      syncope due to IOH. CONCLUSIONS: IOH is highly prevalent among patients with
      previously unexplained syncope. Therefore, beat-to-beat blood pressure
      measurement should be considered in patients with unexplained syncope.

PMID- 30223356
TI  - Assessing the effect of coronary and systemic atherosclerosis following
      myocardial infarction.

PMID- 30223357
TI  - How to select antiplatelet therapy in patients with acute coronary syndrome,
      according to platelet function testing or pharmacogenomic testing?

PMID- 30223358
TI  - Reply to "Letter to editor, Assessing the effect of coronary and systemic
      atherosclerosis following myocardial infarction" by dr Su Yueqiu et al.

PMID- 30223359
TI  - Urate crystals and inflammation. Cardiovascular impact of gout.

PMID- 30223360
TI  - Response to Letter of Li et al.: How to select antiplatelet therapy in patients
      with acute coronary syndrome, according to platelet function testing or
      pharmacogenomic testing?

PMID- 30223361
TI  - Active right atrial emptying fraction predicts reduced survival and increased
      adverse events in childhood pulmonary arterial hypertension.
AB  - BACKGROUND: Right atrial (RA) function has been studied rarely in childhood
      pulmonary arterial hypertension (PAH). We sought to determine if RA and right
      ventricular (RV) area changes measured by echocardiography predicted outcomes.
      METHODS: We reviewed data from children with PAH undergoing cardiac
      catheterization and echocardiography. RA and RV areas were obtained from the
      apical 4-chamber view. Clinical worsening indicated initiation of parenteral
      prostanoid therapy, heart and/or lung transplantation, Potts shunt surgery or
      death. RESULTS: We studied 57 children (27 females), median age 3 years (range
      0.30-17 years), body surface area 0.56 m2 (0.2-1.8), follow up 3 years (0.21
      8.35), time to clinical worsening was 1.14 years (0.03-6.14) and mortality was
      1.55 years (range 0.88-4.95). We determined from receiver operator curves that RA
      active emptying fraction (RA EaF) >=60% predicted clinical worsening (sensitivity
      78%, specificity 69%, AUC 0.7) and mortality (sensitivity 100%, specificity 65%,
      AUC 0.82). RV fractional area change (RVFAC) <25% predicted clinical worsening
      (sensitivity 72%, specificity 79%, AUC 0.85) and death (sensitivity 67%,
      specificity 69%, AUC 0.77). The combination of RA EaF >=60% and RVFAC <33% were
      best predictors of clinical worsening (sensitivity 72%, specificity 82%, partial
      AUC 0.65) and mortality (sensitivity 100%, specificity 77%, partial AUC 0.75).
      CONCLUSION: In childhood PAH, RA EaF >= 60% and RVFAC <25% were associated with
      poor outcomes. RA EaF >=60% and RVFAC <33% were best predictors of clinical
      worsening and may be useful markers in children with PAH who require closer
      observation and more intensive therapy.

PMID- 30223362
TI  - Hybrid repair of thoracoabdominal aneurysm: An alternative strategy for
      preventing major complications in high risk patients.
AB  - BACKGROUND: Nowadays, less invasive endovascular procedures have been employed in
      high risk patients for thoracoabdominal aortic aneurysm (TAAA) in order to try to
      reduce the risk of major complications. The aim of the study was to analyze the
      results of our hybrid 2-stage approach for TAAA repair. METHODS: Between July
      2011 and September 2016, 17 consecutive high-risk patients received a hybrid 2
      stage procedure for TAAA repair. Mean age of the population was 58.9 +/- 9.0
      years and 16 (94.1%) were male. Of them, 7 (41.2%) suffered of chronic
      obstructive pulmonary disease and 15 (88.2%) had a previous history of aortic
      operation. Three patients had Marfan syndrome (17.6%). The preoperative anatomy
      of the aneurysms was classified according to "Crawford classification" in type II
      (n = 6, 35.3%), type III (n = 10, 58.8%) and type IV (n = 1, 5.9%). All patients
      were followed up with an angio CT-scan at 1, 3 months and yearly thereafter.
      RESULTS: In-hospital mortality was 11.8% (2 patient). None of the patients
      experienced paraplegia and paraparesis. Major post-operative complications were
      pancreatitis 17.6% (3/17). At follow-up (mean time of 23.3 +/- 21.7 months) 2
      patient died (12.5%) waiting for the second stage endovascular completion. Median
      interval time between the 2 steps was 35 days. Overall survival at 1- and 3-years
      was 75.6 +/- 1.0. One type Ib and 1 type III endoleak were noted and successfully
      treated with an additional stent graft. CONCLUSIONS: The results of hybrid 2
      stage TAAA repair on high-risk patients are satisfactory and therefore
      encouraging. The extremely low incidence of spinal cord injury could make this
      technique the technique of choice for this type of pathology in selected high
      risk patients. At follow-up, residual endoleaks occur although surgical
      reoperations are not often needed.

PMID- 30223364
TI  - "Wait and watch" is a rational strategy for treating distal tears of acute aortic
      dissection.

PMID- 30223363
TI  - Venous congestion and pulmonary vascular function in Fontan circulation:
      Implications for prognosis and treatment.
AB  - BACKGROUND: Elevation in central venous pressure (CVP) plays a fundamental
      pathophysiologic role in Fontan circulation. Because there is no sub-pulmonary
      ventricle in this system, CVP also provides the driving force for pulmonary blood
      flow. We hypothesized that this would make Fontan patients more susceptible to
      even low-level elevation in pulmonary vascular resistance index (PVRI), resulting
      in greater systemic venous congestion and adverse outcomes. METHODS: Adult Fontan
      patients and controls without congenital heart disease undergoing clinical
      evaluation that included cardiac catheterization and echocardiography were
      examined retrospectively. Outcomes including all-cause mortality and the
      development of Fontan associated diseases (FAD, defined as protein losing
      enteropathy, cirrhosis, heart failure hospitalization, arrhythmia, or
      thromboembolism) were assessed from longitudinal assessment. RESULTS: As compared
      to controls (n = 82), Fontan patients (n = 164) were younger (36 vs 45 years, p <
      0.001), more likely to be on anticoagulation or antiplatelet therapy, and more
      likely to have atrial arrhythmia or cirrhosis. There was a strong correlation
      between CVP and PVRI in the Fontan group (r = 0.79, p < 0.001), but there was no
      such relationship in controls. Elevated PVRI identified patients at increased
      risk for FAD (HR 1.92, 95% CI 1.39-2.41, p = 0.01), and composite endpoint of FAD
      and/or death (HR 1.89, 95% CI 1.32-2.53, p = 0.01) per 1 WU*m2 increment.
      CONCLUSIONS: Systemic venous congestion, which is the primary factor in the
      pathogenesis of FAD and death, is related to even low-level abnormalities in
      pulmonary vascular function. Multicenter studies are needed to determine whether
      interventions targeting pulmonary vascular structure and function can improve
      outcomes in the Fontan population.

PMID- 30223366
TI  - Further insight into 10-year CVD risk evaluation and recommended eligibility for
      statin therapy in Chinese population: Comparison of cardiovascular risk
      prediction models and their guidelines.

PMID- 30223365
TI  - NT-proBNP prognostic value is maintained in elderly and very elderly patients
      with chronic systolic heart failure.
AB  - BACKGROUND: Circulating concentrations of N-terminal fragment of the prohormone
      of brain natriuretic peptide (NT-proBNP) are influenced by age and common age
      related comorbidities, such as renal dysfunction. Therefore, utility of NT-proBNP
      for prediction of prognosis in the aged has been questioned. We aimed to
      investigate the prognostic value of NT-proBNP across age classes in a cohort of
      patients with chronic systolic HF. METHODS AND RESULTS: We enrolled 2364
      consecutive outpatients with HF and left ventricular ejection fraction <=50%.
      Patients were classified according to age quartiles, and a very elderly subgroup
      was identified, aged >=85 years. After baseline assessment (including NT-proBNP
      testing), patients were followed-up for the composite of cardiovascular death,
      heart transplantation or ventricular assistance device implantation (primary
      outcome) and for all-cause death (secondary outcome). Patients in the fourth
      quartile (Q4, age >= 77 years, n = 638) and in the very elderly subgroup (age >=
      85 years, n = 153), had higher NT-proBNP (p < .001 vs Q1). NT-proBNP was
      independently associated with primary and secondary outcome at 1- and 5-years
      follow-up in the whole population, as well as in Q4 and in the very elderly
      subgroup (all p < .05). Compared to the whole population, Q4 and very elderly had
      higher NT-proBNP cut-off for prediction of 1-year primary (4188 and 9729 ng/l,
      respectively vs 3710 ng/l) and secondary outcome (4296 and 7634 ng/l,
      respectively vs 3056 ng/l). CONCLUSIONS: NT-proBNP predicts mortality in elderly
      and very elderly patients with chronic systolic HF, both at mid- and long-term
      follow-up. Higher NT-proBNP prognostic cut-off should be considered in the aged
      HF population.

PMID- 30223367
TI  - Improving diagnosis of left ventricular hypertrophy in Chinese obese individuals:
      Which indexation criteria of left ventricular mass?

PMID- 30223368
TI  - Could red blood cell distribution width predict high CHADS2 and CHADS2-VASC score
      in adults with atrial fibrillation? A focus on the general population.

PMID- 30223369
TI  - Subclinical atherosclerosis and lifestyle realism.

PMID- 30223370
TI  - The emergence of clarifying the role of gut microbes in arrhythmia.

PMID- 30223371
TI  - Response to comment on the original paper entitled "Neural cell adhesion molecule
      1 may be a new biomarker of coronary artery disease".

PMID- 30223372
TI  - Can telomere length predict contrast-induced nephropathy?

PMID- 30223373
TI  - Cardiac rehabilitation ... in a polluted environment?

PMID- 30223374
TI  - Health impacts of the Southeast Asian haze problem - A time-stratified case
      crossover study of the relationship between ambient air pollution and sudden
      cardiac deaths in Singapore.
AB  - OBJECTIVES: To investigate the association between air pollution and out-of
      hospital cardiac arrest (OHCA) incidence in Singapore. DESIGN: A time-stratified
      case-crossover design study. SETTING: OHCA incidences of all etiology in
      Singapore. PARTICIPANTS: 8589 OHCA incidences reported to Pan-Asian Resuscitation
      Outcomes Study (PAROS) registry in Singapore between 2010 and 2015. MAIN OUTCOME
      MEASURES: A conditional Poisson regression model was applied to daily OHCA
      incidence that included potential confounders such as daily temperature,
      rainfall, wind speed, Pollutant Standards Index (PSI) and age. All models were
      adjusted for over-dispersion, autocorrelation and population at risk. We assessed
      the relationship with OHCA incidence and PSI in the entire cohort and in
      predetermined subgroups of demographic and clinical characteristics. RESULTS: 334
      out of 8589 (3.89%) cases survived. Moderate (Risk ratio/RR = 1.1, 95% CI = 1.07
      1.15) and unhealthy (RR =1.37, 95% CI = 1.2-1.56) levels of PSI showed
      significant association with increased OHCA occurrence. Sub-group analysis based
      on individual demographic and clinical features showed generally significant
      association between OHCA incidence and moderate/unhealthy PSI, except in age <
      65, Malay and other ethnicity, traumatic arrests and history of heart disease and
      diabetes. The association was most pronounced among cases age > 65, male, Indian
      and non-traumatic. Each increment of 30 unit in PSI on the same day and previous
      1-5 days was significantly associated with 5.8-8.1% increased risk of OHCA (p <
      0.001). CONCLUSIONS: We found a transient effect of short-term air pollution on
      OHCA incidence after adjusting for meteorological indicators and individual
      characteristics. These finding have public health implications for prevention of
      OHCA and emergency health services during haze.

PMID- 30223375
TI  - Left ventricular diastolic abnormalities other than valvular heart disease in
      antiphospholipid syndrome: An echocardiographic study.
AB  - BACKGROUND: Antiphospholipid syndrome (APS) can be primary or secondary to other
      autoimmune disorders. Besides valvular heart disease (VHD) and coronary artery
      disease (CAD), little is known about the impact of APS on left ventricular (LV)
      function. METHODS: After excluding CAD, relevant VHD and heart failure, 69
      patients (mean age = 43.9 years, 40 with primary and 29 with secondary APS) were
      assessed by echo-Doppler. Sixty-nine heathy controls, matched for age and sex,
      formed the control group. APS was diagnosed in presence of at least one clinical
      criteria and one confirmed laboratory criteria, including lupus anticoagulant
      (LA) titre. The adjusted global APS score (aGAPSS), derived from the combination
      of risk factors for thrombosis and autoimmune-antibody profile was calculated.
      RESULTS: Patients had similar blood pressure and heart rate, but higher body mass
      index (BMI) than controls. LV mass index (p = 0.007) and left atrial volume index
      (p < 0.01) were greater, while early diastolic velocity (e') was lower (p =
      0.003) and E/e' higher (p = 0.007) in APS. Primary APS patients had lower E/A and
      e' compared to both controls and secondary APS, while E/e' was higher in
      secondary APS than in controls. APS patients with diastolic dysfunction were
      older but did not differ for risk factors prevalence from those with
      normal/indeterminate diastolic function. In the pooled APS, LA positivity was
      independently associated with e' and E/e' after adjusting for age, BMI and aGAPSS
      in separate multivariate models. CONCLUSION: In APS, LV diastolic abnormalities
      are detectable. They are more pronounced in primary APS and independently
      associated with LA positivity.

PMID- 30223376
TI  - Infective endocarditis following transcatheter aortic valve replacement:
      Diagnostic yield of echocardiography and associated echo-Doppler findings.
AB  - BACKGROUND: Studies have suggested the diagnostic yield of echocardiography to be
      lower in prosthetic valve endocarditis (PVE) after transcatheter aortic valve
      replacement (TAVR) than reported in surgically-implanted valves but data are
      limited. METHODS: We reviewed transthoracic (TTE) and transesophageal (TEE) echo
      Doppler findings in 17 patients with PVE (13 definite and 4 possible cases
      according to modified Duke criteria) after TAVR at Mayo Clinic, Rochester, MN
      between 2007 and 2016. RESULTS: Median age was 81 years [56; 91] and 5 patients
      (29%) were female. Median Society of Thoracic Surgery predicted risk of mortality
      was 8.8%. PVE occurred 197 days [27; 923] after TAVR. Enterococcus faecalis was
      the most commonly encountered organism (29%). All patients had TEE performed at
      the time of PVE; TTE was performed in 11 patients. TEE was diagnostic for PVE in
      47% of cases and TTE in 18%. TEE was diagnostic in 62% of patients if only
      definite PVE cases are included. Two patients showed prosthetic obstruction at
      the time of PVE; obstruction improved with antibiotic therapy in the surviving
      patient. CONCLUSION: Standard echocardiography techniques had limited diagnostic
      performance in patients with TAVR-related PVE. PVE can present as features of
      TAVR obstruction, thus PVE should also be considered in patients presenting with
      worsening prosthetic obstruction.

PMID- 30223377
TI  - Cardiac magnetic resonance evaluation of left ventricular functional,
      morphological, and structural features in children and adolescents vs. young
      adults with isolated left ventricular non-compaction.

PMID- 30223378
TI  - Safety of intermediate left main stenosis revascularization deferral based on
      fractional flow reserve and intravascular ultrasound: A systematic review and
      meta-regression including 908 deferred left main stenosis from 12 studies.
AB  - BACKGROUND: Current guidelines recommend intravascular ultrasound (IVUS) or
      fractional flow reserve (FFR) to decide upon ambiguous left main (LM) disease.
      However, no study has compared the safety of LM revascularization deferral based
      on FFR or IVUS. METHODS: MEDLINE/PubMed was systematically screened for studies
      reporting on deferred treatment of angiographically ambiguous LM based upon FFR
      or IVUS evaluation. Baseline, angiographic and outcome data were appraised and
      pooled separately for each strategy according to random-effect models with
      inverse-variance weighting. RESULTS: A total of 908 LM stenoses from 7 FFR and 5
      IVUS studies were included with median follow-up of 29.0 and 31.5 months
      respectively. Per year of follow-up occurrence of overall MACE were 5.1% in FFR
      group and 6.4% in IVUS group while death, myocardial infarction, LM
      revascularization were respectively 2.6%, 1.5% and 1.8% vs. 3.0%, 0.5% and 2.2%.
      Meta-regression analysis suggested the influence of a distal LM stenosis on MACE
      in FFR group (beta = 0.06, p = 0.01) and age in IVUS group (beta = 0.4, p =
      0.001). In individual studies several independent predictors of MACE were
      identified including use of lower doses of intracoronary adenosine (OR 1.39, p =
      0.04) in FFR group and plaque burden (OR 1.34, p = 0.025), number of other
      diseased vessels (OR 1.39, p = 0.04) and any untreated stenosis (OR 3.80; p =
      0.037) in IVUS- studies. CONCLUSIONS: Deferring LM intermediate stenosis on the
      basis of FFR or IVUS showed an acceptable and similar risk of events in a mid
      term follow-up. Conversely, several different variables related to each technique
      showed an interaction on outcome.

PMID- 30223380
TI  - Erratum to "Source apportionment of PM10 and PM2.5 air pollution, and possible
      impacts of study characteristics in South Korea" [Environ. Pollut. 240 (2018) 963
      972].

PMID- 30223381
TI  - Ultrasonographic imaging of the effects of continuous, pulsed or sham ultrasound
      treatments on carpal tunnel syndrome: A randomized controlled study.
AB  - BACKGROUND: Clinical and electrophysiological effects of therapeutic ultrasound
      (US) were researched in many studies on patients with CTS with conflicting
      results. OBJECTIVE: To assess the effects of continuous and pulsed US treatments
      by ultrasonographic imaging in addition to clinical and electrophysilogical
      parameters in patients with carpal tunnel syndrome (CTS). METHOD: Fifty-four
      patients with idiopathic CTS were randomly divided into three groups. All
      patients used night splints for two weeks. In addition to splint therapy,
      continuous, pulsed or sham US treatments were applied to patients 10 min/session,
      5 sessions/week for two weeks. Clinical situation (pain, hand function,
      strength), electrophysiological studies (motor distal latency, MDL, sensorial
      distal latency, SDL), and ultrasonographic area measurements of median nerve were
      evaluated. All evaluations were applied at pretreatment (baseline), posttreatment
      (2nd week) and in the 6th week. RESULTS: Whereas significant differences were
      detected for clinical, functional and ultrasonographic imaging findings in each
      group in the 2nd week and 6th week compared to baseline (p< 0.0167 for both), no
      electrophysiological improvements were detected in pulsed-US (p> 0.0167) and only
      improvement for SDL in sham US group in the 2nd week evaluation (p< 0.0167).
      CONCLUSION: According to the results of this study, continuous, pulsed or sham US
      treatments combined with splinting had similar effects on clinical,
      electrophysiological and ultrasonographic imaging improvements. Additionally,
      ultrasonographic imaging may be a preferable objective evaluation tool to prove
      the early posttreatment clinical improvements when electrophysiological changes
      could not be detected.

PMID- 30223379
TI  - Myocardial fibrosis and its relation to adverse outcome in transposition of the
      great arteries with a systemic right ventricle.
AB  - BACKGROUND: Myocardial dysfunction has been implicated in gradual heart failure
      in transposition of the great arteries (TGA) with a systemic right ventricle
      (RV). Fibrosis can be assessed using the extracellular volume fraction (ECV). Our
      aim was to measure ECV and determine its associations with clinical findings and
      outcomes. METHODS: We prospectively measured ECV in systemic RV subjects (either
      D-loop after atrial switch or L-loop) and healthy controls. T1 measurements for a
      single mid-ventricular short-axis plane before and 3, 7, and 15 min after
      gadolinium contrast were used to quantify systemic ventricular ECV. Individuals
      with elevated ECV were compared to those without. RESULTS: In 53 TGA subjects
      (age 34.6 +/- 10.3 years, 41% female) the mean ECV for the systemic RV (28.7 +/-
      4.4%) was significantly higher than the left ventricle in 22 controls (26.1 +/-
      2.8%, P = 0.0104). Those with an elevated ECV (n = 15, 28.3%) had a higher b-type
      natriuretic peptide (BNP) (P < 0.011) and a longer 6-min walk distance (P =
      0.021), but did not differ by age, arrhythmia history, ventricular volume,
      function, or circulating collagen byproducts. At follow-up (median 4.4 years),
      those experiencing major cardiovascular endpoints (new arrhythmia, arrhythmia
      device, heart failure hospitalization, listing for transplantation, mechanical
      support, or cardiovascular death, n = 14) had a higher ECV. ECV, age, and BNP
      were independent predictors of cardiac events in Cox-proportional hazard models.
      CONCLUSIONS: Myocardial fibrosis is common in the systemic RV and associated with
      a higher BNP. Elevated CMR-derived ECV was associated with adverse clinical
      outcome. The findings suggest a role of diffuse myocardial fibrosis in clinical
      deterioration of the systemic RV.

PMID- 30223382
TI  - Dysphagia and aspiration pneumonia in elderly hospitalization stroke patients:
      Risk factors, cerebral infarction area comparison.
AB  - OBJECTIVE: Stroke is the most common neurological disease that is associated with
      deglutition disorders. The aim of this study was to analyze dysphagia and
      aspiration pneumonia risk factors in post-stroke elderly inpatients. METHOD: We
      consecutively enrolled 212 stroke patients over sixty years of age from July 2014
      to June 2015. Seventeen patients were eliminated. Stroke patients' demographics,
      clinical symptoms and biochemistry data were collected. Modified water swallowing
      test was used for the assessment of deglutition difficulty. These inpatients were
      classified into two groups: territorial anterior circulation infarction (n= 114)
      and territorial posterior circulation infarction (n= 82). Finally, dysphagia and
      aspiration pneumonia risk factor were analyzed between these two groups. RESULT:
      Number of previous cerebral infarction, national institute of health stroke scale
      (NIHSS) score, masticatory muscle paralysis, abolition of gag reflex were
      correlated with the deglutition difficulty in these patients. In addition, NIHSS
      score (p= 0.017) and dysphagia (p= 0.02) were correlated with aspiration
      pneumonia. CONCLUSION: In stroke inpatients over sixty years of age, it is
      necessary to distinguish the patients with multiple previous cerebral
      infarctions, high NIHSS score, masticatory muscle paralysis, abolition of gag
      reflex for early detection and rehabilitation of dysphagia.

PMID- 30223383
TI  - Comparison of the demographic and clinical characteristics, functional status and
      quality of life of lower extremity amputees to identify the reason for undergoing
      amputation.
AB  - OBJECTIVE: The aim of the study was to evaluate and compare clinical and
      demographic characteristics, functional status and quality of life among patients
      who underwent amputation for the most common reason in our region. METHODS:
      Demographic data, level of and reasons for undergoing amputation and clinical
      data on the use of prostheses in 126 patients were recorded. The amputees were
      divided into three groups: vascular, trauma and landmine. Variables related to
      clinical and demographic characteristics, daily life activities and quality of
      life were investigated. Duration of prosthesis use, daily walking distance with
      prosthesis, 10-m walking speed with the prosthesis and 6-min walking distance of
      the amputees were recorded. The Short Form-36, Turkish version of the Trinity
      Amputation and Prosthesis Experience Scales and Beck Depression Inventory were
      used to evaluate the patients' quality of life. The residual limb pain scale was
      used to evaluate the severity of pain. RESULTS: Comparison between the amputees
      in the trauma and vascular groups showed highly significant results (P< 0.001) in
      amputees in the trauma group with respect to all parameters of daily life
      activities, functional status and quality of life. Comparison between the
      vascular and landmine amputees showed significant results (P< 0.001) in the
      landmine amputees with respect to all parameters except emotional role
      functioning, social functioning and mental health. Comparison between the
      amputees in the trauma and landmine groups showed no significant results (P>
      0.05) with respect to all parameters expect emotional role functioning and mental
      health. CONCLUSIONS: While the clinical and demographic characteristics,
      functional status and quality of life parameters were similar in the amputees in
      the trauma and landmine groups, they showed statistically significant differences
      in almost all parameters compared with those in vascular amputees.

PMID- 30223384
TI  - Granular cell tumor: A report of three cases and review of literature.
AB  - OBJECTIVE: In order to improve the understanding of granular cell tumor and avoid
      missing the best time of treatment, we report three patients with rare granular
      cell tumors admitted to our hospital in the past 10 years. METHODS: The
      characteristics, methods of treatment, postoperative pathological results and
      follow-up results of three cases of granular cell tumor were analyzed; and
      literatures related to granular cell tumors were reviewed. RESULTS: All patients
      underwent surgical treatment, and the excised lesions were sent to the laboratory
      for testing. Postoperative pathological results were as follows: granular cell
      tumor of the vulva, granular cell tumor within the sheath of the rectus muscle,
      and granular cell tumor in the left cubit nerve. All three cases were benign, and
      no recurrence was found during follow-ups after the operation. CONCLUSION:
      Granular cell tumors are rare tumors derived from the nerve sheath, are mostly
      benign tumors, and the incidence of malignancy is 2%. The gold standard for
      diagnosis of granular cell tumor is histopathology. Granular cell tumor is not
      sensitive to radiotherapy and chemotherapy, and needs to be surgically removed.
      Since this disease may have no solid lesions and tumor cells can infiltrate local
      tissues, based on the full excision of the lesion, the extent of resection may be
      extended to areas without infiltration. This disease has a possibility of
      recurrence, and patients need to be followed-up.

PMID- 30223385
TI  - miR-503 is down-regulated in osteosarcoma and suppressed MG63 proliferation and
      invasion by targeting VEGFA/Rictor.
AB  - We analyzed the expression of miR-503 in osteosarcoma tissues (OS) and discussed
      the clinical significance of our findings. To provide a theoretical basis for
      clinical applications, prognosis prediction and treatment of osteosarcoma, we
      studied the biological function of miR-503 and its mechanism in MG63 osteosarcoma
      cells. Real-time polymerase chain reaction (PCR) was used to detect the
      expression of miR-503 in 45 OS tissues and 20 osteochondroma tumors, analyzing
      the relationship between clinical pathology and follow-up data. Cox multivariate
      analysis revealed the clinical and pathological features of the osteosarcoma
      index and the influence of miR-503 expression on OS prognosis. To observe the
      effect on cell proliferation and invasion, MG-63 cells were transfected with miR
      503. The TargetScan and PicTar bioinformatics method was used to analyze the
      probable target gene of miR-503 and, combined with the function of the target
      genes, resulted in a final validation of related pathways. miR-503 was
      significantly down-regulated in primary OS samples (26/45, 57.8%). The median miR
      503 expression level in osteosarcoma was two-fold lower than that in
      osteochondroma (median expression 6.4 and 13.09, respectively, P< 0.05). The less
      expressed miR-503 was associated with Enneking stage (p= 0.004) and invasion (p=
      0.015) of OC. Patients with low miR-503 expression had poorer overall survival
      time. In the multivariate analysis, miR-503 was a significant prognostic factor
      (P= 0.010). miR-503 can inhibit proliferation and invasion in the MG63 cell line.
      Using bioinformatics, VEGFA and Rictor were determined to be the likely
      downstream target genes of miR-503. VEGFA, Rictor, Akt and Erk1/2 were negatively
      regulated by the overexpression of miR-503. In conclusion, miR-503 has
      significant tumor-suppressor biological activity and is thus likely to become a
      new target for the treatment of osteosarcoma.

PMID- 30223386
TI  - Diagnostic and prognostic value of serum miR-99a expression in oral squamous cell
      carcinoma.
AB  - BACKGROUND: Despite progress in the treatment of oral squamous cell carcinoma
      (OSCC) over past years, the prognosis for OSCC patients remains dismal. MicroRNA
      99a (miR-99a) has been found to involve in the development of many cancer types,
      but its clinical role in OSCC is unclear. OBJECTIVE: The aim of this study was to
      explore the clinical implications of serum miR-99a in OSCC. METHODS: This study
      detected serum miR-99a levels in 121 OSCC cases and 55 healthy controls by using
      quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis.
      RESULTS: The data showed that serum miR-99a expression was significantly
      decreased in OSCC patients compared with normal controls. OSCC patients with low
      miR-99a expression experienced more frequent poor differentiation and advanced
      clinical stage. Furthermore, in screening OSCC cases from normal controls, miR
      99a could yield a receiver-operating characteristic (ROC) area under the curve
      (AUC) of 0.911 with 83.6% specificity and 80.2% sensitivity. Notably, patients
      with high miR-99a expression had longer overall survival and recurrence free
      survival. Finally, serum miR-99a was identified to be an independent prognostic
      indicator for OSCC. CONCLUSIONS: These results suggested that miR-99a might be a
      valuable marker for the prediction of early detection and prognosis in OSCC.

PMID- 30223387
TI  - Soluble LAG3 acts as a potential prognostic marker of gastric cancer and its
      positive correlation with CD8+T cell frequency and secretion of IL-12 and INF
      gamma in peripheral blood.
AB  - OBJECTIVE: Gastric cancer (GC) is the second most common lethal cancer worldwide
      and lymphocyte-activation gene 3 (LAG3) as a therapeutic target for cancers has
      been investigated. Herein, our study is to clarify the value of peripheral blood
      (PB) soluble LAG-3 (sLAG3) in GC. METHODS: Peripheral serum samples of GC
      patients and healthy people were collected for the measurement of serum levels of
      sLAG3, carcinoembryonic antigen (CEA), IL-12 and IFN-gamma. Additionally, ROC and
      Kaplan-Meier curves were adopted to identify the diagnostic and prognostic values
      of sLAG-3 in patients with GC. Then, GC-bearing mice were treated with
      recombinant sLAG3. The tumor volume was measured, and CD8+T cell frequency was
      detected in PB and tumor-ininfiltrating area. Additionally, the expression of IL
      12 and IFN-gamma in T cells was assayed and the overall survival of mice was
      analyzed. RESULTS: sLAG3 in PB was poorly expressed and its expression was
      positively correlated with IL-12 and IFN-gamma expression in GC patients. sLAG3
      was proved to have a higher diagnostic value than CEA in GC. Moreover, high sLAG
      3 expression is found in relation to a better prognosis in GC. The in vivo
      experiments indicated that sLAG-3 might inhibit the tumor growth, and promote the
      secretion of CD8+T cells, IL-12 and IFN-gamma. Furthermore, sLAG-3 was able to
      prolong overall survival and increase survival rate of GC-bearing mice.
      CONCLUSION: Based on these findings, we conclude that sLAG3 positively regulates
      CD8+T cells, IL-12 and IFN-gamma, and function as a prognostic marker for GC,
      which might be a potential target in the treatment of GC.

PMID- 30223388
TI  - Katanin P80 expression correlates with lymph node metastasis and worse overall
      survival in patients with breast cancer.
AB  - OBJECTIVE: The aim of this study was to investigate the correlation of katanin
      P80 expression with clinicopathological features and overall survival (OS) in
      surgical breast cancer (BC) patients. METHODS: Four hundred and fourteen BC
      patients underwent surgery were analyzed in this retrospective cohort study.
      Katanin P80 expression was examined by immunofluorescence assay. The median
      follow-up duration was 118.0 months (quantiles: 99.0-140.5 months), the last
      follow-up date was Jul 1st 2017. RESULTS: Eighty-five patients (20.5%) with
      katanin P80 positive expression and 329 patients (79.5%) with katanin P80
      negative expression were observed in this research. Katanin P80 positive
      expression was correlated with higher N stage (p< 0.001) and TNM stage (p<
      0.001). K-M curve and log-rank test revealed that katanin P80 positive patients
      presented with shorter OS compared with katanin P80 negative patients (p< 0.001).
      Multivariate Cox's regression analysis disclosed that katanin P80 positive
      expression (p< 0.001) and histologic grade (p< 0.001) could independently predict
      unfavorable OS. Furthermore, subgroups analysis was performed, which illuminated
      that katanin P80 positive expression was correlated with shorter OS in all
      subgroups divided by molecular subtyping and TNM stage (all p< 0.05) except in
      TNM stage I subgroup (p= 0.573). CONCLUSION: Katanin P80 expression positively
      correlated with lymph node metastasis and could abe a novel biomarker for
      prognosis in BC patients.

PMID- 30223389
TI  - Ubiquitin-specific protease 22 promotes the proliferation, migration and invasion
      of glioma cells.
AB  - Ubiquitin-specific protease 22 (USP22), as one of the 11 death-from-cancer
      signature genes, presented high expression in a variety of tumors. Previous
      studies showed that USP22 played a significant role in cell-cycle, oncogenesis,
      clinicopathology and survival. Our studies have presented USP22 was over
      expressed in glioma tissue and the patients with high expression of USP22 had a
      poor survival than that with low expression of USP22. However, the concrete
      effect of USP22 on biological behavior in glioma cells has been rarely reported.
      The study aimed to clear the effect of USP22 on cell proliferation, migration and
      invasion in glioma. Using siRNA, USP22 was knocked down in U251 and U87 glioma
      cells and successful transfection effect was validated. Cell proliferation,
      migration and invasion were observed by the methods of EdU, Wound healing and
      Transwell assay, separately. At the same time, the expression of MMP2 was
      detected by Gelatin zymography after transfecting siRNAs. After the knockdown of
      USP22 by siRNA, the abilities of glioma cell proliferation, migration and
      invasion were decreased, accompanying, the expression of MMP2 was also decreased.
      We drew a conclusion that USP22 could increase the abilities of proliferation,
      migration and invasion of glioma cells, and promote the growth and development of
      glioma.

PMID- 30223390
TI  - Downregulated GBX2 gene suppresses proliferation, invasion and angiogenesis of
      breast cancer cells through inhibiting the Wnt/beta-catenin signaling pathway.
AB  - OBJECTIVE: Gastrulation brain homeobox 2 (GBX2), a gene involved in mid/hindbrain
      region, has been revealed as one of the oncogene associated with certain cancers,
      as an example being prostate cancer. However, despite years of worldwide
      research, the underlying mechanism of GBX2 as well as its significance in breast
      cancer still remains unclear. Therefore, the present study evaluates the
      abilities of GBX gene silencing providing for the proliferation, invasion and
      angiogenesis of breast cancer cells by way of the Wnt/beta-catenin signaling
      pathway. METHODS: We employed a microarray analysis to screen out differentially
      expressed genes relative to breast cancer. Moreover, we retrieved GBX2 expression
      in breast cancer to find out the relationship between GBX2 expression and
      prognosis in breast cancer. We performed RT-qPCR to screen out cell lines with
      high GBX2 expression. Subsequently, both RT-qPCR and western blot analysis were
      employed so as to measure the combination of the mRNA and protein expressions of
      GBX2, beta-catenin, vascular endothelial growth factor (VEGF), matrix
      metalloproteinase (MMP)-2, and MMP-9. The effect that GBX2 gene silencing and the
      Wnt/beta-catenin signaling pathway had on cell proliferation, invasion,
      angiogenesis, and tumorigenic ability were evaluated. RESULTS: GBX2 gene was also
      identified having played a role in breast cancer development due to its
      association with the Wnt/beta-catenin signaling pathway. GBX2 gene silencing was
      found to be an inhibitor for the mRNA and protein expressions regulating beta
      catenin, VEGF, MMP-2, and MMP-9. Cell proliferation, invasion, angiogenesis, as
      well as tumorigenic ability in breast cancer were investigated and found to have
      been suppressed by the GBX2 gene silencing or inactivation of the Wnt/beta
      catenin signaling pathway. CONCLUSION: The study has made an attempt to provide
      evidence to the idea that GBX2 gene silencing has an inhibition effect on the
      proliferation, invasion and angiogenesis of the breast cancer cells by inhibiting
      the activation of the Wnt/beta-catenin signaling pathway.

PMID- 30223391
TI  - Contribution of smoking habit to the prognosis of stage I KRAS-mutated non-small
      cell lung cancer.
AB  - BACKGROUND: One of the known risk factors for non-small cell lung cancer (NSCLC)
      is somatic mutation in the Kirsten rat sarcoma (KRAS) gene. The relationship with
      smoking is well known. METHODS: We retrospectively studied the data of 92
      patients who underwent pulmonary resection January 2003 and June 2012 and were
      diagnosed as KRAS-mutated pathological stage I adenocarcinoma. RESULTS: Among
      them, 33 patients who were non to light smoker (NLS) (smoking index, 0 to 400)
      were compared with 59 middle to heavy smoker (MHS) (> 400). The 5-year overall
      survival (OS) was significantly better in NLS (96.9%) than in MHS (80.0%);
      however, no significant difference was observed compared with wild-type KRAS
      (92.8%) (p= 0.66). The presence of p53 was significantly associated with smoking
      history (p< 0.01). The 5-year OS for NLS with p53-negative KRAS codon 12-mutated
      NSCLC (n= 28) was significantly better (96.3%) than that for MHS with both p53
      positive and -negative KRAS mutation (p= 0.03 and p< 0.03, respectively).
      CONCLUSIONS: A non to light smoking habit might contribute to an improvement in
      prognosis that is equivalent to that of wild-type KRAS, and p53 mutation did not
      affect survival in smokers harboring KRAS codon 12.

PMID- 30223393
TI  - Antibody drug conjugates: Progress, pitfalls, and promises.
AB  - Antibody drug conjugates (ADC's) represent a promising and an efficient strategy
      for targeted cancer therapy. Comprised of a monoclonal antibody, a cytotoxic
      drug, and a linker, ADC's offer tumor selectively, reduced toxicity, and improved
      stability in systemic circulation. Recent approvals of two ADC's have led to a
      resurgence in ADC research, with more than 60 ADC's under various stages of
      clinical development. The therapeutic success of future ADCs is dependent on
      adherence to key requirements of their design and careful selection of the target
      antigen on cancer cells. Here we review the main components in the design of
      antibody drug conjugates, improvements made, and lessons learned over two decades
      of research, as well as the future of third generation ADCs.

PMID- 30223392
TI  - Comparison of circulating DNA from plasma and urine for EGFR mutations in NSCLC
      patients.
AB  - PURPOSE: The need for less invasive procedures for lung cancer probing is
      critically needed to better understand the disease. The purpose of the current
      study aims to explore the use of circulating tumor DNA (ctDNA) derived from
      plasma and urine specimens. METHODS: Matched peripheral blood and morning urine
      specimens were obtained from 160 late stage NSCLC patients. The amount of ctDNA
      was quantified for each of the patients. Activating and sensitizing EGFR
      mutations commonly found in NSCLC patients were profiled. Longitudinal analysis
      was performed to compared DNA variations during disease progression. RESULTS:
      Measurement of EGFR mutations in NSCLC patients using plasma and urinal DNA
      demonstrated strong concordance to conventional tissue biopsy profiling. Baseline
      matched tumor samples yielded 82.8% and 84.0% for plasma and urinal DNA
      respectively. For these measurements, the positive predictive value was 100% for
      plasma and urinal DNA. In the longitudinal study, we observed strong links to
      disease severity and survival analysis showed a clear trend with patients having
      higher DNA concentrations to have worse outcome especially for urinal DNA. HR for
      patients stratified using plasma and urinal DNA were 1.23 and 2.55 respectively.
      CONCLUSION: Measurements of circulating DNA within body fluids presented
      potentially new tools for the disease management of NSCLC patients with EGFR
      mutations. We demonstrated both plasma and urinal DNA correlated well to tissue
      biopsies and were potentially prognostic to address patients' survival outcome.

PMID- 30223394
TI  - The anti-penicillin antibodies levels in sensitive and insensitive people to
      intradermal skin test.
AB  - BACKGROUND: The hypersensitivity reaction to penicillin is a public health
      problem. Immunological responses to penicillin and other beta-lactam antibiotics
      can be classified into immediate and non-immediate responses. The immediate
      hypersensitivity is mediated by IgE; however, the non-immediate sensitivity is
      facilitated by other isotypes of antibody or T lymphocytes. OBJECTIVE: This
      research detected the non-IgE antibody value against penicillin in allergic and
      normal people. METHODS: Thirty-eight samples from patients with positive or
      negative intradermal skin testing results of penicillin allergy were included in
      this study. The total antibody and IgM levels against penicillin G were defined
      by in-house ELISA test. RESULTS: The results showed a significant (P< 0.05)
      elevation in total immunoglobulin and non-IgM anti-penicillin antibody of
      sensitive groups; however, the anti-penicillin IgM was significantly greater in
      non-sensitive peoples. CONCLUSIONS: Although the sensitized people to penicillin
      cannot be certainly detected with the total antibody, specific IgG and IgM value
      against penicillin, these values are good indicators for prediction of immediate
      and late response of the immune system to penicillin.

PMID- 30223395
TI  - Shear-Induced Amyloid Formation in the Brain: IV. Effects on Synapses Surrounding
      Senile Plaque and in Plaque-Free Regions.
AB  - Amyloid-beta oligomers (AbetaO) have been proposed as neurotoxins in the synaptic
      dysfunction that precedes Alzheimer's disease symptoms. Human and animal model
      studies report that senile plaques contain a halo of AbetaO molecules surrounding
      these plaques. A far smaller number of oligomers are distributed widely in plaque
      free regions. It has been suggested that oligomers migrate from halos to nearby
      synapses and are incorporated into both pre- and postsynaptic terminals. These
      two types of oligomers have two different toxicities when extracted and injected
      in animal models. This paper proposes a shear-energy based explanation for the
      data in these studies. Shear hypotheses in the preceding three papers in this
      series are applied to suggest how the hydrodynamics and resulting shear patterns
      explain the spatial distribution of both AbetaO types, the apparent synapse loss
      in the vicinity of plaque particles, and possible reasons for the differing
      toxicities. A shear-based mechanism is proposed for the preferential migration of
      locally shear-excited Abeta molecules into the synaptic cleft. It is proposed
      that high energy laminar shear generated by the forced diversion of interstitial
      fluid around the flow-impeding plaque particle is responsible for the formation
      of AbetaOs around the plaque. It is suggested that in plaque-free regions, a
      different type of AbetaO with different toxicity is generated by lower energy
      shear flow around synapses, depositing AbetaO within the synapse from either the
      neuron membrane surface or by prion-like seeding within the synaptic cleft by
      locally-sheared Abeta molecules near the synapse entry.

PMID- 30223396
TI  - Chronic Traumatic Encephalopathy and Neurodegeneration in Contact Sports and
      American Football.
AB  - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease
      characterized by the presence of abnormally phosphorylated tau protein in the
      depths of one or more cortical sulci. Controversy over the risk of CTE and
      neurologic disorders later in life among contact sport athletes has taken hold in
      the public spotlight, most notably in American football. Players, parents,
      coaches, and legislators have taken action based on the commonly held notion that
      contact sports invariably lead to neurodegenerative disorders. However, to fully
      understand the science behind this assumed association, a critical appraisal of
      the evidence is warranted. With regards to CTE in sports, the objectives of the
      current report are to: 1) describe the history of CTE, 2) review current CTE
      definitions, 3) critically evaluate the empiric data, divided into all contact
      sports and exclusively American football, and 4) summarize notable themes for
      future research.

PMID- 30223397
TI  - Periodontal Pathogens and Associated Intrathecal Antibodies in Early Stages of
      Alzheimer's Disease.
AB  - BACKGROUND: Recent studies suggest a link between periodontitis and Alzheimer's
      disease (AD). OBJECTIVE: Verification of the presence of periodontal pathogens
      and the intrathecal generation of pathogen-specific antibodies in 20 patients
      with AD and 20 with other forms of dementia (DEM-noAD). METHODS: Clinical
      periodontal indices were recorded. Cerebrospinal fluid (CSF) was analyzed for
      total tau protein (T-tau) and amyloid-beta (Abeta1-42). In serum and CSF,
      antibody levels against Porphyromonas gingivalis, Aggregatibacter
      actinomycetemcomitans, and Treponema species were quantified. The presence of
      selected bacteria and inflammatory biomarkers were determined in periodontium,
      serum, and CSF. RESULTS: In line with diagnoses, CSF-levels of Abeta1-42 were
      significantly lower in AD than DEM-noAD patients. Periodontal destruction and
      inflammation were omnipresent with no difference between groups. P. gingivalis,
      T. forsythia, and Treponema species were detected in more than 50% of subgingival
      biofilm samples, but neither in serum nor in the CSF. Elevated levels of anti
      pathogen antibodies in CSF of 16 patients (7 AD; 9 DEM-noAD) compared to serum
      highlight a possibility of the intrathecal immune response to pathogens. There
      was no significant difference in antibodies levels against selected bacteria in
      CSF and serum between groups. Multivariate regression analysis and general linear
      models revealed an association of the T-tau level in AD group with both serum
      levels of anti-P. gingivalis antibodies and MCP-1/CCL-2. CONCLUSION: Periodontal
      pathogens may enter the brain and stimulate a local immune response. However, in
      patients with dementia at the age up to 70 years, periodontal pathogens do not
      act as a trigger for developing AD.

PMID- 30223398
TI  - Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease.
AB  - Clarifying the relationships between neuropsychiatric symptoms and Alzheimer's
      disease (AD)-related pathology may open avenues for effective treatments. Here,
      we investigate the odds of developing neuropsychiatric symptoms across increasing
      burdens of neurofibrillary tangle and amyloid-beta pathology. Participants who
      passed away between 2004 and 2014 underwent comprehensive neuropathologic
      evaluation at the Biobank for Aging Studies from the Faculty of Medicine at the
      University of Sao Paulo. Postmortem interviews with reliable informants were used
      to collect information regarding neuropsychiatric and cognitive status. Of 1,092
      cases collected, those with any non-Alzheimer pathology were excluded, bringing
      the cohort to 455 cases. Braak staging was used to evaluate neurofibrillary
      tangle burden, and the CERAD neuropathology score was used to evaluate amyloid
      beta burden. The 12-item neuropsychiatric inventory was used to evaluate
      neuropsychiatric symptoms and CDR-SOB score was used to evaluate dementia status.
      In Braak I/II, significantly increased odds were detected for agitation, anxiety,
      appetite changes, depression, and sleep disturbances, compared to controls.
      Increased odds of agitation continue into Braak III/IV. Braak V/VI is associated
      with higher odds for delusions. No increased odds for neuropsychiatric symptoms
      were found to correlate with amyloid-beta pathology. Increased odds of
      neuropsychiatric symptoms are associated with early neurofibrillary tangle
      pathology, suggesting that subcortical neurofibrillary tangle accumulation with
      minimal cortical pathology is sufficient to impact quality of life and that
      neuropsychiatric symptoms are a manifestation of AD biological processes.

PMID- 30223400
TI  - Albuminuria and Microalbuminuria as Predictors of Cognitive Performance in a
      General Population: An 11-Year Follow-Up Study.

PMID- 30223402
TI  - Assessment Battery for Children with Developmental Coordination Disorder (ABCD):
      Preliminary report of tool development and clinical application.
AB  - PURPOSE: Development of an easy to use tool for the assessment of Developmental
      Coordination Disorder that is applicable to Indian children. METHODS: The steps
      for instrument development were followed stringently. In order to ensure the
      robustness of the tool, psychometric properties were determined with 127 children
      attending various schools. The Winsteps program was used to analyze data for a
      Rasch model analysis. RESULTS: The Kaiser-Meyer-Olkin Measure of Sampling
      Adequacy (KMO) analysis showed an acceptable limit. The real item separation
      reliability of 4.84 demonstrates that the items of this tool create a well
      defined variable. CONCLUSION: This study met the objectives that it attempted to.
      The final tool consists of two versions- the Assessment Battery for Children with
      coordination Disorder-Short Version (ABCD-SV) consisting of 12 items, and the
      ABCD-FV consisting of 20 items. ABCD fulfills criterion A and B of the Diagnostic
      and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria for Developmental
      Coordination Disorder (DCD).

PMID- 30223401
TI  - Motor Function Test Reliability During the NeuroNEXT Spinal Muscular Atrophy
      Infant Biomarker Study.
AB  - BACKGROUND: The NeuroNEXT SMA Infant Biomarker Study, a two year, longitudinal,
      multi-center study of infants with SMA type 1 and healthy infants, presented a
      unique opportunity to assess multi-site rater reliability on three infant motor
      function tests (MFTs) commonly used to assess infants with SMA type 1. OBJECTIVE:
      To determine the effect of prospective MFT rater training and the effect of rater
      experience on inter-rater and intra-rater reliability for the Test of Infant
      Motor Performance Screening Items (TIMPSI), the Children's Hospital of
      Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) and the Alberta
      Infant Motor Scale (AIMS). METHODS: Training was conducted utilizing a novel set
      of motor function test (MFT) videos to optimize accurate MFT administration and
      reliability for the study duration. Inter- and intra-rater reliability of scoring
      for the TIMPSI and inter-rater reliability of scoring for the CHOP INTEND and the
      AIMS was assessed using intraclass correlation coefficients (ICC). Effect of
      rater experience on reliability was examined using ICC. Agreement with 'expert'
      consensus scores was examined using Pearson's correlation coefficients. RESULTS:
      Inter-rater reliability on all MFTs was good to excellent. Intra-rater
      reliability for the primary MFT, the TIMPSI, was excellent for the study
      duration. Agreement with 'expert' consensus was within predetermined limits
      (>=85%) after training. Evaluator experience with SMA and MFTs did not affect
      reliability. CONCLUSIONS: Reliability of scores across evaluators was
      demonstrated for all three study MFTs and scores were reproducible on repeated
      administration. Evaluator experience had no effect on reliability.

PMID- 30223403
TI  - Factors affecting procedural pain in children during and immediately after
      intramuscular botulinum toxin injections for spasticity.
AB  - PURPOSE: To evaluate variables that modulate pain during intramuscular botulinum
      toxin A injections in children. METHODS: As part of a Quality Improvement
      project, this retrospective analysis compared reported pain during and five
      minutes post injections with patient and procedural variables using subgroup and
      regression analyses (N= 593 procedures with 249 unique patients). RESULTS: Mean
      procedural pain for all procedures (n= 563) was 3.8 +/- 3.0. Most children
      reported no pain (83.8%) or mild pain (12.1%) five minutes after the procedure.
      Provider, previous patient experience, and dose did not significantly impact
      pain. Linear regression analysis (R=2 0.64) demonstrated that younger age (p<
      0.05), use of vapo-coolant spray or topical anesthetic (p< 0.01), and body region
      injected (p< 0.01) were significantly associated with increased procedural pain.
      Logistic regression (R=2 0.14) demonstrated that pain during the procedure (p<
      0.001) and older age (p< 0.01) increased the likelihood of pain post-procedure.
      Utilization of personnel for distraction did not significantly predict pain
      ratings at either time point. CONCLUSION: Age, topical anesthesia, and injected
      region impact procedural pain and in nearly 96% of cases, patients report mild or
      no pain within five minutes. Additional research into these predictors is
      necessary, but short-lived procedural pain may suggest that frequent use of
      sedation/anesthesia is unnecessary.

PMID- 30223404
TI  - Development and validation of a modified performance-oriented mobility assessment
      tool for assessing mobility in children with hypophosphatasia.
AB  - PURPOSE: To modify the Performance-Oriented Mobility Assessment-Gait (POMA-G)
      subtest and validate this modified POMA-G (mPOMA-G) in children with
      hypophosphatasia (HPP), a rare metabolic disorder that can manifest with
      musculoskeletal symptoms that impair mobility and ambulation. METHODS: Based on
      feedback from an expert panel, the POMA-G was modified by removing gait
      initiation/path assessments and expanding the rating scale for step
      length/continuity to capture aspects of observational gait analysis relevant to
      children with HPP. Three trained physical therapists used the mPOMA-G for video
      based assessments of gait in 14 children with childhood HPP who participated in a
      clinical study of asfotase alfa or in a natural history study. Intraclass
      correlation coefficients (ICCs) were calculated to determine interrater and
      intrarater agreement. Concurrent validity was evaluated by correlations with
      other validated assessment tools. RESULTS: Across 192 observations from available
      videos, interrater and intrarater agreement of mPOMA-G scores was significant
      (ICCs: 0.76 for both; P< 0.001). mPOMA-G scores had strong concurrent validity
      with the Childhood Health Assessment Questionnaire, Pediatric Outcomes Data
      Collection Instrument Transfer and Mobility Scale, Sports and Physical Function
      subscale, and 6-Minute Walk Test (all P? 0.0002). CONCLUSION: The mPOMA-G is a
      reliable and valid measure for detecting clinically significant impairments in
      children with HPP.

PMID- 30223405
TI  - The effectiveness of biofeedback therapy in managing Bladder Bowel Dysfunction in
      children: A systematic review.
AB  - PURPOSE: The purpose of this study was to examine the effects of biofeedback
      therapy as a non-invasive intervention to treat Bladder Bowel Dysfunction in
      pediatrics. METHODS: Six databases were searched between February 2016 and
      September 2016. Biofeedback studies for children aged 4-16 with idiopathic
      urinary or fecal incontinence were included. Articles were excluded on subjects'
      medical histories, study design, timeline of study, and lacking expert review.
      Quality was determined using Sackett's Levels of Evidence and the PEDro scale.
      RESULTS: Twelve articles were included in the review. Quality of evidence was
      moderate, as the average PEDro score of the selected articles was 5.3. The
      participants' ages ranged from 4-16 years old. Studies demonstrated that a
      multifactorial approach consisting of biofeedback therapy and behavioral
      modification can be successful in resolving Bladder Bowel Dysfunction.
      CONCLUSION: Biofeedback is a beneficial treatment for children with dysfunctional
      voiding and functional fecal incontinence. More conclusive research needs to be
      completed to explore the effects of biofeedback therapy treatment to make more
      concrete conclusions. Healthcare professionals should consider biofeedback as an
      alternative approach in conjunction with traditional treatments. A
      multidisciplinary approach is best when treating dysfunctional voiding and
      functional fecal incontinence in the pediatric population.

PMID- 30223406
TI  - Decreasing pediatric pain and agitation during botulinum toxin injections for
      spasticity with virtual reality: Lessons learned from clinical use.
AB  - PURPOSE: Recurrent botulinum toxin (BoNT) injections are used in the pediatric
      population for management of spasticity, but the procedure is often associated
      with significant pain and anxiety for patients. Non-pharmacologic treatment
      alternatives for procedural discomfort are limited. Immersive virtual reality
      (VR) has shown efficacy in treatment of procedural discomfort in pediatric
      patients. A retrospective chart review was performed to assess feasibility and
      use of treating BoNT procedure-related discomfort in pediatric patients with VR.
      METHODS: Fourteen patients undergoing elective BoNT injections viewed VR videos
      using a mobile VR headset during the procedure. Face, Legs, Activity, Cry,
      Consolability scale (FLACC) scores were obtained and feedback was elicited
      following injections. RESULTS: The VR intervention was well tolerated, and
      patients' guardians requested that it be used again in 9/14 cases. The remainder
      either had high FLACC scores despite VR and neutral or negative guardian
      impressions of intervention, or were unable to utilize the device. CONCLUSION: VR
      was helpful in reducing BoNT procedure-related discomfort in a majority of
      patients. Challenges with VR setup, patient tolerance, and selecting viewing
      experiences were identified to guide further research and use of VR in a clinical
      environment.

PMID- 30223407
TI  - Design and feasibility study of human body communication transceiver based on
      FDM.
AB  - BACKGROUND: The body area networks (BAN) are built by many wearable sensors to
      record, monitor or control the vital signals within the human body continuously.
      Human body communication (HBC) is a novel physical layer method to implement the
      BAN with low power consumption, low radiation, and strong anti-interference.
      However, the most existing HBC rarely consider the situation in which multiple
      sensors transmit data at the same time. OBJECTIVE: The aim of this paper is to
      investigate the feasibility of frequency division multiplexing for human body
      communication multiplex data transmission. METHODS: The signal was injected into
      the human body, and the human channel gain was measured by the spectrum analyzer.
      Two frequency signals were selected with smaller gain to design the transceiver.
      The transmitter used OOK modulation technology to design each functional unit,
      and the receiver recovered the original signal with a non-coherent demodulation
      method. RESULTS: The experimental results show that after the dual signals were
      transmitted through the human body, the receiver could recover the original
      signal correctly. In both static and dynamic situations, even if the transmission
      rate was as high as 115.2 kb/s, the bit error rate was only 10-4. CONCLUSIONS:
      The frequency division multiplexing scheme can be selected for multi-channel data
      transmission in human body communication.

PMID- 30223408
TI  - Raising awareness of hand-arm vibration syndrome (HAVS) using posters.
AB  - BACKGROUND: Hand-arm vibration syndrome (HAVS) is caused by prolonged
      occupational exposure to hand-transmitted vibration. Although HAVS is
      preventable, disease awareness and prevention knowledge are lacking in high-risk
      workplaces; this may contribute to under-diagnosis, delays in seeking care, and
      poor health outcomes. Posters may be used to increase awareness in the workplace.
      OBJECTIVE: To conduct a pilot survey in workers with HAVS about poster use in
      their workplaces, their recommendations for poster campaigns and training
      programs, and their evaluation of HAVS awareness and prevention posters. METHODS:
      All eligible HAVS patients in the Occupational Health Clinic at St. Michael's
      Hospital, in Toronto, Canada, were asked to complete a questionnaire on workplace
      poster use and to evaluate a set of HAVS posters. RESULTS: Fifty workers
      participated; almost all were males, aged 50 and older, working in construction.
      Most indicated having non-HAVS specific awareness posters in their workplaces.
      There was a positive evaluation of the design, content, and potential usefulness
      of the posters. The poster depicting finger blanching stood out most. The poster
      depicting anti-vibration gloves rated highest for relatability and effectiveness
      at conveying disease importance. CONCLUSIONS: Participants supported the proposed
      use of industry-specific HAVS awareness posters in their workplaces. Future
      research should evaluate the effectiveness of these posters in the workplace.

PMID- 30223409
TI  - Concordance of assessments of clients' mental and behavioral health with in vivo
      assessment of work performance.
AB  - BACKGROUND: Assessing functioning and disability among individuals with mental
      and behavioral health disorders has historically relied on deriving accurate
      psychiatric diagnoses and assessing symptoms. However, growing empirical evidence
      suggests that this approach is inadequate to determine real world performance,
      particularly with respect to work. OBJECTIVE: We examined a performance-based
      approach to the assessment of work functioning and its relationship to mental and
      behavioral health status. METHODS: A cross-sectional study was conducted at two
      mental health programs. Trained employment providers conducted performance-based
      assessments of work function and ratings of mental and behavioral health while
      study participants self-reported their mental/behavioral health functioning. We
      hypothesized that participant and provider ratings of mental/behavioral health
      would be moderately correlated with performance-based assessments of work
      function. RESULTS: We found no significant correlation between participants' self
      report of their mental and behavioral health and performance-based assessments of
      work. Employment providers' ratings of participants' mental/behavioral health
      were moderately correlated with performance-based measures of work. Finally, we
      found low concordance between employment providers and study participants' with
      respect to ratings of their mental/behavioral health. CONCLUSIONS: Contrary to
      our hypotheses, ratings of mental/behavioral health were only moderately
      correlated with performance-based measures of work. Results confirm earlier
      research suggesting that it is difficult to predict work performance from
      participants' self-reports of their mental/behavioral health alone. Performance
      based assessments of work capacity as well as ratings of mental and behavioral
      health may both be needed for a more complete and complimentary picture of the
      ability of individuals with mental and behavioral health disorders to function in
      the work place.

PMID- 30223410
TI  - Dynamics of an orthopaedic team: Insights to improve teamwork through a design
      thinking approach.
AB  - BACKGROUND: Supporting teamwork in healthcare is a way to foster both the quality
      and safety of care, and better working conditions for all the team members.
      Although increasing attention is paid to this topic on a general level, there is
      less knowledge about its unfolding in orthopaedic units and its translation to
      interventions. OBJECTIVE: To identify concrete opportunities for teamwork
      intervention through a design thinking approach by analysing the teamwork
      dynamics of an orthopaedic team. METHODS: An adaptation of the learning history
      method, comprising shadowing, observations and interviews involving 26
      orthopaedic team members at a top clinical teaching hospital in the Netherlands,
      was applied. A thematic analysis was conducted to derive themes that describe
      team dynamics and to subsequently extrapolate opportunities for intervention.
      RESULTS: We identified five themes and translated them into four design
      opportunities for intervention, namely: a) Improve daily rounds by reducing
      cognitive overload and promoting confidence; b) Improve collaboration by building
      empathy; c) Connect the patient with the professional team; and d) Support
      changes by fostering learning. Suggestions for concrete actions are presented for
      each opportunity. CONCLUSIONS: Opportunities to improve teamwork among healthcare
      professionals, specifically those in orthopaedics, revolve around the creation of
      common knowledge, the fostering of mutual understanding, and the design of tools
      and activities that support these processes.

PMID- 30223411
TI  - Awareness and perceptions of ergonomic programs between workers and managers
      surveyed in the construction industry.
AB  - BACKGROUND: Work-related musculoskeletal injuries and disorders (WMSDs) are among
      the most frequently reported causes of lost or restricted work time in the
      construction industry. Ergonomics is still a relatively new theme for the
      construction industry. Understanding of the workers' and managers' knowledge and
      perception of ergonomic issues in construction can play a critical role to
      develop and implement effective ergonomic programs and policies. OBJECTIVE: To
      study the similarities and differences of the workers' and managers' knowledge
      and perceptions of ergonomics matters in the construction industry. METHODS: A
      survey questionnaire was developed and distributed to both workers and management
      personnel employed by sixteen different construction contractors performing
      various types of construction work. The final questionnaire comprised of a total
      of forty questions and consisted of four major sections: background, safety and
      ergonomic programs, injuries and illnesses, and work conditions. RESULTS: Eighty
      eight workers and managers completed the survey questionnaire. Nearly all of
      their employer had a written safety program, while only one third had an
      ergonomics program. Ergonomics was perceived as relatively less important
      compared to the safety issues. Managers were more likely to think that management
      encourages feedback from site employees than were workers. Managers appeared to
      be more likely to know that their companies have an ergonomic training program or
      policy than were workers. Workers were more likely to consider to purchase or
      select the ergonomic hand tools than were managers. Workers and managers alike
      reported having slight regard for the potential occurrence of a work-related
      musculoskeletal disorder. CONCLUSIONS: While the construction industry has done
      an admirable job developing safety programs, it has done far less to develop
      comprehensive ergonomic programs and policies that would help provide education
      and guidance to its workers and managers in the industry.

PMID- 30223412
TI  - Methodological quality of service learning studies in rehabilitation professions:
      A systematic review.
AB  - BACKGROUND: Service-learning (SL) has been widely implemented and grown as a
      pedagogy in the rehabilitation professions. However, assessment on the quality of
      evidence for the effectiveness of SL related to student learning outcomes and the
      scope of SL activities related to the occupation of work in the rehabilitation
      professions is not available. OBJECTIVE: This systematic review was to evaluate
      the rigor of the methodological quality of SL studies and the scope of SL
      activities related to the occupation of work in the rehabilitation professions.
      METHODS: We performed a systematic on-line electronic literature search of nine
      bibliographic databases available through the university library system to
      identify peer-reviewed journal articles on SL provided by the tri-alliance of
      rehabilitation professional students, with the primary or secondary outcome on
      the evaluation of student SL experiences. Twenty-two SL articles using
      experimental design between 1995 and 2016 were extracted as they qualified for
      the methodological appraisal. Appraisal of each article was performed
      independently by four investigators using the Effective Public Health Practice
      Project Quality Assessment Tool for Quantitative Studies. RESULTS: In six of the
      22 SL studies (27%), service provided by the rehabilitation professional students
      was related to the occupation of work (i.e., assessment, prevention of illness,
      injury, and disability, and intervention). There was a significant increase in
      the number (and percent) of SL studies related to the occupation of work compared
      to that of a previous systematic review (0%, P = 0.03, Fisher's exact test).
      Results from the evaluation of the methodological quality of these 22 reviewed
      articles revealed that all received a global rating score of weak. The low
      methodological quality rating of the reviewed articles was mainly attributed to
      not controlling for confounders (22 articles), non-blinding (21), and using
      outcome measures which did not have evidence to support their validity (14).
      Inability to control for confounders was related to weak research design as more
      than 77% of the reviewed articles used quasi-experimental designs without a
      control group. Non-blinding was related to the self-report nature of the outcome
      measures. CONCLUSIONS: A significant increase in the number of SL studies related
      to the occupation of work was found, which may provide an indirect indication on
      an increase in the capacity to provide (work) rehabilitation services. However,
      selected studies demonstrated high risk of bias which limited firm conclusions to
      be drawn on reported findings from SL in the tri-alliance of rehabilitation
      professions curricula.

PMID- 30223413
TI  - If it isn't finished at five, then I'll continue until it is. A qualitative study
      of work pressure among employees in vocational education.
AB  - BACKGROUND: Prolonged work pressure can contribute to burnout. The Job-Demands
      Resources model (the health impairment process and the roles of job and personal
      resources in it) provides a framework for studying work pressure. OBJECTIVE: The
      study aims were to understand the experiences of employees in the career services
      and a teaching department of a school for vocational education regarding the
      following: A) work pressure; B) its negative consequences; and C) how job
      resources and D) personal resources play a role in the employees' experience of
      work pressure or in helping to cope with it. METHODS: A qualitative study based
      on 11 in-depth interviews with teachers (5) and supporting personnel (6) was
      performed at a Dutch organization for vocational education. The interviews were
      analyzed interpretatively. RESULTS: A) The teachers and supporting personnel
      generally experienced work pressure, which had both qualitative and quantitative
      aspects. B) The consequences included working overtime and lower job performance.
      Factors such as autonomy and social support from colleagues were C) job
      resources, and moving from idealism towards realism was D) a personal resource.
      CONCLUSIONS: Both the teachers and supporting personnel who were interviewed
      experienced work pressure and its related consequences, as well as job and
      personal resources. Work pressure may threaten the sustainable employability of
      these employees.

PMID- 30223414
TI  - Safety culture maturity assessment for mining activities in South America.
AB  - BACKGROUND: Health and safety is a crucial issue in the mining industry due to
      the implication of accidents in the sector. OBJECTIVE: This study determines the
      safety culture characteristics in several mining activities from South America.
      METHODS: A survey of the safety culture maturity has been done by means of 24
      questions regarding the type of activity, number of employees and safety culture
      characteristics of the activity: information of accidents and incidents,
      organizational structure to deal with information, involvement of the company in
      health and safety issues, the way it communicates accidents and incidents and
      commitment of the company towards health and safety. RESULTS: The questionnaire
      was completed by 62 managers from Bolivia, Peru and Colombia. Results show
      different behaviors depending on the type of company, Artisanal or Large-Scale
      Mines, ASM and LSM respectively. LSM show a level of maturity according to the
      size of the company, while ASM does not have a clear trend in terms of size, even
      though there is a relationship between employees and safety culture maturity. In
      addition, a remarkable difference can be seen between activities with and without
      continuous improvement systems implemented. CONCLUSIONS: Large scale mining
      improves their level of safety culture as the size of the company increases,
      because procedures and control systems are implemented. Cooperatives or small
      companies also achieve substantial gains when they introduce similar systems.

PMID- 30223415
TI  - Effectiveness of a multifactorial ergonomic intervention and exercise
      conditioning kinesiology program for subsequent work related musculoskeletal
      disorder prevention.
AB  - BACKGROUND: Health care workers are known to be at high risk for occupational
      musculoskeletal disorders and injuries. Many different intervention strategies
      have been implemented in order to reduce the risk of injury to health care
      workers, however not many have been proven to be effective. A continuing care
      establishment in Ottawa, Canada, implemented a multidimensional kinesiology
      intervention program for injured employees. OBJECTIVE: To evaluate the
      effectiveness of the kinesiology intervention program on reducing subsequent
      rates for the nursing personnel and analyze the impact of age, position (RN, RPN,
      PCA) and sex on subsequent injuries. METHODS: The number of recorded work related
      musculoskeletal disorders (WRMSD) for each patient care worker was counted from
      2007-2011. The control group included injured employees that were not referred to
      the kinesiologists, or who chose not to participate in the program. The
      intervention group included injured employees that were referred to the
      kinesiology service and followed their treatment program. RESULTS: The
      intervention group showed a statistically significant reduction of subsequent
      acute cases when compared to the control group. Nevertheless there was no
      significant impact regarding age, position or sex on subsequent acute cases.
      CONCLUSION: The kinesiology intervention program within the health care facility
      was effective at reducing subsequent WRMSD rates within the nursing personnel.

PMID- 30223416
TI  - Variation, companionship and manageability important for recovery during working
      hours: A qualitative focus group study.
AB  - BACKGROUND: Lack of recovery from everyday strains and demands is connected to
      increased levels of stress-related problems and development of ill-health. There
      is much research on how to handle and prevent fatigue and stress in leisure time,
      but research on working time is more scarce. A recent study found that employees'
      experience of recovery during working hours was related to high self-rated
      health. OBJECTIVE: The aim of this study was to explore the concept of recovery
      during working hours among primary health care workers. METHODS: Eight focus
      groups with 50 staff members, men and women, from different professions were
      conducted in the primary health care sector in southern Sweden. The analysis was
      inspired by systematic text condensation, a strategy for qualitative analysis.
      RESULTS: Three main categories were identified as important factors for
      experiencing recovery during working hours: variation (including changes in
      location, tasks and tempo) companionship (including helpfulness, appreciation,
      social chat and laughter) and manageability (including completion, satisfaction,
      influence, control and reflection). CONCLUSIONS: Recovery during working hours is
      multifaceted. The categories identified in this study will be further elaborated
      and tested.

PMID- 30223417
TI  - Bullying experiences of dental interns working at four dental institutions of a
      developing country: A cross-sectional study.
AB  - BACKGROUND: Bullying is an aggressive and violent behavior marked by repetitive
      harassment of a weaker victim, which may also occur in the workplace including
      healthcare settings. Although extensively studied in the west, bullying of
      workers in the healthcare setting is largely underexplored in the South Asian
      context. OBJECTIVE: The aim of our study was to explore the phenomena of
      workplace bullying among dental interns in selected dental institutes of Karachi,
      Pakistan. METHODS: A cross-sectional study was conducted among dental interns
      working at four dental institutions in Karachi, Pakistan. The Negative acts
      questionnaire (NAQ-R), a standardized, validated tool was administered to
      identify bullying experiences among dental interns over the past six months; in
      addition, demographic information of participants as well as details about their
      exposure to bullying was collected. A multivariable binary logistic regression
      was used to identify the correlates of bullying in this population. The study was
      performed and reported according to the STROBE guidelines. Data was analyzed
      using STATA 12.0 and SPSS 19.0. RESULTS: A total of 125 participants were
      included in our analysis. Bullying prevalence among dental interns based on the
      operational definition by Mikkelsen stood at 36.8%, while self-labelled bullying
      was observed in 55 %. Males and participants from private institutions were more
      likely to self-label themselves as victims. 67% of respondents reported having
      witnessed bullying. Clinical faculty was identified as the most common
      perpetrator (23%) followed by colleagues 20% and the dental support staff 17%.
      Report of bullying among victims was low (14.5%) the most common reason being
      that "complaining is of no use" (28.8%) and "being afraid of the consequences"
      (22%). CONCLUSIONS: The results of the study indicate a high prevalence of
      bullying in the participating dental institutions. Our results indicate a clear
      need to implement antiviolence regulations, anti-bullying educational programs
      and advocate further research on interventions to minimize bullying, enhance
      learning and professional engagement of interns in dental institutions.

PMID- 30223418
TI  - A tentative efficiency index for pointing device use in computer aided design: A
      pilot study.
AB  - BACKGROUND: Focusing on the efficiency aspect of computer pointing devices'
      usability, this paper reports on a novel and tentative empirically derived
      efficiency index for 3D CAD. OBJECTIVE: Three commercially available computer
      pointing devices were compared: a standard horizontal computer mouse, a vertical
      device (supporting neutral pronation of the forearm) and a slanted device.
      METHODS: Pilot structured observations of 10 subjects' activity were carried out
      to estimate the proportion of each unique computer mouse operation during CAD
      modelling with a 3D parametric software. Pointing, dragging and steering
      standardized tasks were implemented by software and performed by 20 users.
      Effectiveness and efficiency were calculated and discomfort, effort and ease of
      use were subjectively assessed. RESULTS: The mean efficiency index value was
      lower for the vertical device. Assessments of discomfort, effort and ease of use
      also supported considering preference for the horizontal and slanted devices,
      providing limited internal validation. CONCLUSION: Results suggest the tentative
      index may offer a valid means of ranking performance of alternative pointing
      devices regarding operation efficiency.

PMID- 30223419
TI  - Development and experimental verification of an ergonomic shopping bag handle.
AB  - BACKGROUND: Plastic shopping bags are used world over. However, users may suffer
      pain in or injury to their fingers because of the relatively thin plastic handles
      of those bags. Due to such drawbacks of the available bag handles, new designs
      are needed. OBJECTIVE: The purpose of this study was to develop a handle that can
      be used to carry many bags simultaneously. This handle was ergonomically designed
      and manufactured with soft grip. Then, an experiment was performed to test the
      usefulness of the developed handle. METHODS: The cardiac cost, discomfort
      ratings, activity levels of eight muscles, and peak plantar pressure (PPP) were
      the response variables in the experiment. The carrying style (with or without the
      handle), carrying method (dominant hand or both hands), and weight carried (5%,
      10%, or 15% of the subject's body weight) were the independent variables in the
      experiment. Twenty-six healthy, young volunteers participated in the experiment.
      RESULTS: It was found that carrying grocery bags in both hands using the bag
      handle was preferable to the other carrying methods because it reduced the
      cardiac cost, muscular stress, PPP, and average discomfort ratings. CONCLUSION:
      The results of this study demonstrated that the developed shopping bag handle
      provides an ergonomic solution for carrying multiple heavy plastic bags.

PMID- 30223420
TI  - Young, vulnerable and uncertain: Young workers' perceptions of work health and
      safety.
AB  - BACKGROUND: Young workers are at an increased risk of work place injury, and are
      less likely to report hazards or injuries, or apply for workers' compensation
      even though they are over-represented in workers' compensation statistics in
      comparison with their older peers. OBJECTIVE: To identify young workers'
      perceptions of work health and safety (WHS), why and how they report (or do not
      report) hazards and injuries, and examine where they source WHS information. This
      paper reports on the first stage of a larger, mixed methods study on WHS and
      young workers in South Australia. METHODS: A total of 226 young South Australian
      workers aged between 12 and 25 years completed an online survey. Data were
      analyzed using chi-squared analysis for categorical variables and t-tests where
      the dependent variable was continuous. RESULTS: Three quarters of young workers
      identified stress at work, not being trained to do the job, fatigue from work and
      lifting heavy things at work as WHS issues, although not necessarily as issues
      that they have personally experienced. Most young workers obtained information
      about WHS through their employer although a sizable proportion sourced this
      information from friends and social media. Young workers identified that they
      lacked confidence to report WHS issues. When they did report issues, many young
      workers reported these issues to their parents, despite identifying that their
      parents were often unable to help. CONCLUSIONS: Our findings contribute to our
      understanding of young workers' perceptions of work health and safety. Although
      young workers could identify their concerns about particular health and safety
      related issues at work, they lacked the confidence to report their concerns and
      had limited information about where to go for help. The research suggests that
      there is a need to empower young people to report WHS concerns to their employer
      and provide structures and processes that encourage reporting.

PMID- 30223421
TI  - Dynamic magnetic resonance imaging of carbogen challenge on awake rabbit brain at
      1.5T.
AB  - BACKGROUND: Anesthesia may alter the cellular components contributing to the
      magnetic resonance imaging (MRI) signal intensities. Developing awake animal
      models to evaluate cerebral function has grown in importance. OBJECTIVE: To
      investigate a noninvasive strategy for dynamic MRI (dMRI) of awake rabbits during
      carbogen challenge. METHODS: A nonmetallic assistive device with a self-adhering
      wrap secure procedure was developed for the head fixation of awake rabbits. Multi
      shot gradient echo echo-planar imaging sequence was applied for the dMRI on a 1.5
      T clinical MRI scanner with a quadrature head coil. The carbogen challenge
      pattern was applied in a sequence of air - carbogen - air - carbogen - air.
      Twelve scans were performed for each block of carbogen challenge. T2-weighted
      fast-spin echo and T1-weighted gradient echo sequences were performed before and
      after dMRI to evaluate the head position shifts. The whole dMRI scan time was
      about 30 minutes. RESULTS: The position shift of 8 rabbits in the x-and y
      direction was less than 3%. The average MRI signal intensities (SI) from the 8
      rabbits during carbogen challenge was fitted well using exponential growth and
      decay functions. The average MRI SI increase due to carbogen inhaling was 1.51%.
      CONCLUSIONS: The proposed strategy for head dMRI on an awake rabbit during
      carbogen challenge is feasible.

PMID- 30223422
TI  - A correlative study of myocardial infarction scar characteristics by DE-MR and
      the Lown's classification of ventricular premature beats.
AB  - OBJECTIVE: Correlation between myocardial infarction (MI) scar by cardiac
      magnetic resonance and the Lown's classification of ventricular premature beats
      (VPBs) is poorly understood. This study aims to investigate the correlation
      between the MI scar characteristics by delayed-enhancement magnetic resonance
      imaging (DE-MRI) and the Lown's classification of VPBs. METHODS: Sixty-five
      patients, in the convalescence stage and consolidation phase of MI, were included
      in this retrospective study. All patient were divided into VPBs group (n = 39)
      and non-VPBs group (n = 26 patients) according to the clinical diagnostic
      criteria of Universal Definition of MI scar. VPBs patients were assigned to
      Lown's I-II group and Lown's III-IV subgroup in accordance with the Lown
      classification criteria. Cardiac function parameters and MI scar characteristics
      were detected by cardiac magnetic resonance (CMR) and DE-MRI, respectively.
      RESULTS: Lown's classification was negatively correlated with left ventricular
      ejection fraction (LVEF), peak ejection rate (PER) and peak filling rate (PFR) (-
      0.724, - 0.628, - 0.559), and positively correlated with MI area, MI integral, MI
      segments number and left ventricular end systolic volume (LVESV) (0.673, 0.655,
      0.586, and 0.514), respectively.CONCLUSIONSThe study indicated that MI area and
      MI integral were strongly associated with Lown's classification.

PMID- 30223423
TI  - Comparison of medical image classification accuracy among three machine learning
      methods.
AB  - BACKGROUND: Low-quality medical images may influence the accuracy of the machine
      learning process. OBJECTIVE: This study was undertaken to compare accuracy of
      medical image classification among machine learning methods, as classification is
      a basic aspect of clinical image inspection. METHODS: Three types of machine
      learning methods were used, which include Support Vector Machine (SVM),
      Artificial Neural Network (ANN), and Convolution Neural Network (CNN). To
      investigate changes in accuracy related to image quality, we constructed a single
      dataset using two different file formats of DICOM (Digital Imaging and
      Communications in Medicine) and JPEG (Joint Photographic Experts Group). RESULTS:
      The JPEG format contains less color information and data capacity than the DICOM
      format. CNN classification was accurate for both datasets, whereas SVM and ANN
      accuracy decreased with the loss of data from DICOM to JPEG formats. CONCLUSIONS:
      CNN is more accurate than conventional machine learning methods that utilize the
      manual feature extraction.

PMID- 30223425
TI  - Three-Dimensional S/CeO2/RGO Composites as Cathode Materials for Lithium-Sulfur
      Batteries.
AB  - In this paper, the synthesis of the three-dimensional (3D) composite of spherical
      reduced graphene oxide (RGO) with uniformly distributed CeO2 particles is
      reported. This synthesis is done via a facile and large-scalable spray-drying
      process, and the CeO2/RGO materials are hydrothermally compounded with sulfur.
      The morphology, composition, structure, and electrochemical properties of the 3D
      S/CeO2/RGO composite are studied using X-ray diffraction (XRD), scanning electron
      microscope (SEM), transmission electron microscopy (TEM), thermal gravimetric
      analysis (TGA), Raman spectra and X-ray photoelectron spectroscopy (XPS), etc.
      The electrochemical performance of the composites as electrodes for lithium
      sulfur batteries is evaluated. The S/CeO2/RGO composites deliver a high initial
      capacity of 1054 mAh g-1, and retain a reversible capacity of 792 mAh g-1 after
      200 cycles at 0.1 C. Profiting from the combined effect of CeO2 and RGO, the
      CeO2/RGO materials effectively inhibit the dissolution of polysulfides, and the
      coating of spherical RGO improves the structural stability as well as
      conductivity.

PMID- 30223424
TI  - Phosphatidylethanolamine Induces an Antifibrotic Phenotype in Normal Human Lung
      Fibroblasts and Ameliorates Bleomycin-Induced Lung Fibrosis in Mice.
AB  - Lung surfactant is a complex mixture of phospholipids and specific proteins but
      its role in the pathogenesis of interstitial lung diseases is not established.
      Herein, we analyzed the effects of three representative phospholipid components,
      that is, dipalmitoilphosphatidylcoline (DPPC), phosphatidylglycerol (PG) and
      phosphatidylethanolamine (PE), on collagen expression, apoptosis and Ca2+
      signaling in normal human lung fibroblasts (NHLF) and probed their effect in an
      experimental model of lung fibrosis. Collagen expression was measured with RT
      PCR, apoptosis was measured by using either the APOPercentage assay kit (Biocolor
      Ltd., Northern Ireland, UK) or the Caspase-Glo 3/7 assay (Promega, Madison, WI,
      USA) and Ca2+ signaling by conventional epifluorescence imaging. The effect in
      vivo was tested in bleomycin-induced lung fibrosis in mice. DPPC and PG did not
      affect collagen expression, which was downregulated by PE. Furthermore, PE
      promoted apoptosis and induced a dose-dependent Ca2+ signal. PE-induced Ca2+
      signal and apoptosis were both blocked by phospholipase C, endoplasmic reticulum
      pump and store-operated Ca2+ entry inhibition. PE-induced decrease in collagen
      expression was attenuated by blocking phospholipase C. Finally, surfactant
      enriched with PE and PE itself attenuated bleomycin-induced lung fibrosis and
      decreased the soluble collagen concentration in mice lungs. This study
      demonstrates that PE strongly contributes to the surfactant-induced inhibition of
      collagen expression in NHLF through a Ca2+ signal and that early administration
      of Beractant enriched with PE diminishes lung fibrosis in vivo.

PMID- 30223426
TI  - Freeze-Thaw Durability of Strain-Hardening Cement-Based Composites under Combined
      Flexural Load and Chloride Environment.
AB  - Cement-based materials are usually not exposed to an independent deterioration
      process but are exposed to a combination of mechanical load and environmental
      effects. This paper reports the frost resistance durability of strain-hardening
      cement-based composites (SHCC) under combined flexural loading at different
      levels and under chloride attack. The loss of mass, dynamic elastic modulus, and
      microstructure characteristics of SHCC specimens were determined, and the
      influence of loading level on frost resistance was analyzed. In addition, the
      effect of freeze-thaw action on the flexural performance and diffusion properties
      of chloride in SHCC under the combined loads was investigated. The results show
      that the process of degradation was accelerated due to the simultaneous action of
      flexural loading and freeze-thaw cycles in the chloride environment, and SHCC
      suffered more serious damage at a higher loading level. However, flexural
      strength decreased by only 13.87% after 300 freeze-thaw cycles at load level S =
      0.36. The diffusion properties of chloride in SHCC under constant flexural
      loading were affected by the freezing and thawing cycle. The free chloride
      concentration Cf increased with the development of freezing and thawing at the
      same diffusion depth, and a bilinear relationship was found between the chloride
      diffusion coefficient Dc and the number of freeze-thaw cycles.

PMID- 30223427
TI  - The Effect of Long-Term Administration of Fatty Acid Amide Hydrolase Inhibitor
      URB597 on Oxidative Metabolism in the Heart of Rats with Primary and Secondary
      Hypertension.
AB  - Fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl] N
      cyclohexylcarbamate (URB597) may influence redox balance and blood pressure
      through the modulation of endocannabinoids levels. Therefore, this study aimed to
      compare changes in oxidative metabolism and apoptosis in the hearts of rats with
      spontaneous hypertension (SHR) and secondary hypertension (11-deoxycorticosterone
      acetate; DOCA-salt rats) treated by URB597 via intraperitoneal injection for 14
      days. The results showed that URB597 decreased the activity of NADPH and xanthine
      oxidases in both groups of rats. Moreover, in the heart of SHR rats, URB597 led
      to an increase of enzymatic and nonenzymatic antioxidant activity and levels
      (catalase, vitamin C, glutathione/glutathione disulfide [GSH/GSSG]) and
      upregulation of the thioredoxin system; however, NRf2 expression was
      downregulated. The opposite effect in relation to Nrf2 activity and the
      thioredoxin system was observed in DOCA-salt rats after URB597 administration.
      Despite improvement in antioxidant parameters, URB597 enhanced oxidative
      modifications of phospholipids (4-hydroxynonenal and isoprostanes) and proteins
      (carbonyl groups) in SHR heart, whereas 4-hydroxynonenal and carbonyl groups
      levels decreased in the heart of DOCA-salt rats. Obtained results suggest that
      examined lipid mediators are involved in peroxisome proliferator-activated
      receptors (PPAR)-independent and PPAR-dependent modulation of cardiac
      inflammatory reactions. Furthermore, decreased expression of pro-apoptotic
      proteins (Bax and caspase 3 and 9) was observed after URB597 administration in
      the heart of both groups of hypertensive rats, whereas expression of the
      antiapoptotic protein (Bcl-2) increased in SHR rats. Long-term administration of
      URB597 altered cardiac redox status depending on the type of hypertension. URB597
      enhanced oxidative metabolism and reduced pro-apoptotic factors in the heart of
      SHR rats, increasing the probability of heart metabolic disorders occurrence or
      progression.

PMID- 30223428
TI  - Asymmetric Synthesis of (-)-6-Desmethyl-Fluvirucinine A1 via Conformationally
      Controlled Diastereoselective Lactam-Ring Expansions.
AB  - The versatile synthesis of (-)-6-desmethyl-fluvirucinine A1 was accomplished at a
      24% overall yield through a thirteen-step process from a known vinylpiperidine.
      The key part involved the elaboration of the distal stereocenters and a
      macrolactam skeleton via conformationally-induced diastereocontrol and the
      iterative aza-Claisen rearrangements of lactam precursors.

PMID- 30223429
TI  - Fusion of Heart Rate, Respiration and Motion Measurements from a Wearable Sensor
      System to Enhance Energy Expenditure Estimation.
AB  - This paper presents a new method that integrates heart rate, respiration, and
      motion information obtained from a wearable sensor system to estimate energy
      expenditure. The system measures electrocardiography, impedance pneumography, and
      acceleration from upper and lower limbs. A multilayer perceptron neural network
      model was developed, evaluated, and compared to two existing methods, with data
      from 11 subjects (mean age, 27 years, range, 21-65 years) who performed a 3-h
      protocol including submaximal tests, simulated work tasks, and periods of rest.
      Oxygen uptake was measured with an indirect calorimeter as a reference, with a
      time resolution of 15 s. When compared to the reference, the new model showed a
      lower mean absolute error (MAE = 1.65 mL/kg/min, R2 = 0.92) than the two existing
      methods, i.e., the flex-HR method (MAE = 2.83 mL/kg/min, R2 = 0.75), which uses
      only heart rate, and arm-leg HR+M method (MAE = 2.12 mL/kg/min, R2 = 0.86), which
      uses heart rate and motion information. As indicated, this new model may, in
      combination with a wearable system, be useful in occupational and general health
      applications.

PMID- 30223431
TI  - Severity of Sjogren's Syndrome Keratoconjunctivitis Sicca Increases with
      Increased Percentage of Conjunctival Antigen-Presenting Cells.
AB  - This study investigated the relationship between clinical severity and percentage
      of conjunctival antigen-presenting cells (APCs) in Sjogren's syndrome (SS)
      associated keratoconjunctivitis sicca (KCS). KCS clinical severity was based on
      symptom severity, tear volume, tear break-up time, and ocular surface dye
      staining. Conjunctival goblet cell density (GCD) was measured in periodic acid
      Schiff (PAS)-stained membranes. Conjunctival cells obtained by impression
      cytology were used for flow cytometry to measure percentages of CD45+HLA-DR+ APCs
      and mature CD11c+CD86+ dendritic cells (DCs). Compared to normal conjunctiva, the
      percentages of HLA-DR+ and CD11c+CD86+ cells were higher in the conjunctiva of
      the KCS group (p < 0.05). The percentage of CD45+HLA-DR+ cells positively
      correlated with clinical severity (r = 0.71, p < 0.05) and negatively correlated
      with GCD (r = -0.61, p < 0.05). Clinical severity also negatively correlated with
      GCD (r = -0.54, p < 0.05). These findings indicate that a higher percentage of
      APCs and mature DCs in the conjunctiva is associated with more severe KCS in SS.
      These APCs may contribute to the generation of the pathogenic Th1 cells that
      cause goblet cell loss in KCS.

PMID- 30223432
TI  - Genome-Wide Identification and Analysis of Apple NITRATE TRANSPORTER 1/PEPTIDE
      TRANSPORTER Family (NPF) Genes Reveals MdNPF6.5 Confers High Capacity for
      Nitrogen Uptake under Low-Nitrogen Conditions.
AB  - The NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER family (NPF) proteins play
      important roles in moving substrates such as nitrate, peptides, amino acids,
      dicarboxylates, malate, glucosinolates, indole acetic acid (IAA), abscisic acid
      (ABA), and jasmonic acid. Although a unified nomenclature of NPF members in
      plants has been reported, this gene family has not been studied as thoroughly in
      apple (Malus * domestica Borkh.) as it has in other species. Our objective was to
      provide general information about apple MdNPFs and analyze the transcriptional
      responses of some members to different levels of nitrate supplies. We identified
      73 of these genes from the apple genome and used phylogenetic analysis to
      organize them into eight major groups. These apple NPFs are structurally
      conserved, based on alignment of amino acid sequences and analyses of
      phylogenetics and conserved domains. Examination of their genomic structures
      indicated that these genes are highly conserved among other species. We monitored
      14 cloned MdNPFs that showed varied expression patterns under different nitrate
      concentrations and in different tissues. Among them, NPF6.5 was significantly
      induced by both low and high levels of nitrate. When compared with the wild type,
      35S:MdNPF6.5 transgenic apple calli were more tolerant to low-N stress, which
      demonstrated that this gene confers greater capacity for nitrogen uptake under
      those conditions. We also analyzed the expression patterns of those 73 genes in
      various tissues. Our findings benefit future research on this family of genes.

PMID- 30223430
TI  - The PIN-FORMED Auxin Efflux Carriers in Plants.
AB  - Auxin plays crucial roles in multiple developmental processes, such as
      embryogenesis, organogenesis, cell determination and division, as well as tropic
      responses. These processes are finely coordinated by the auxin, which requires
      the polar distribution of auxin within tissues and cells. The intercellular
      directionality of auxin flow is closely related to the asymmetric subcellular
      location of PIN-FORMED (PIN) auxin efflux transporters. All PIN proteins have a
      conserved structure with a central hydrophilic loop domain, which harbors several
      phosphosites targeted by a set of protein kinases. The activities of PIN proteins
      are finely regulated by diverse endogenous and exogenous stimuli at multiple
      layers-including transcriptional and epigenetic levels, post-transcriptional
      modifications, subcellular trafficking, as well as PINs' recycling and turnover
      to facilitate the developmental processes in an auxin gradient-dependent manner.
      Here, the recent advances in the structure, evolution, regulation and functions
      of PIN proteins in plants will be discussed. The information provided by this
      review will shed new light on the asymmetric auxin-distribution-dependent
      development processes mediated by PIN transporters in plants.

PMID- 30223433
TI  - A Comparison of Vitamin E Status and Associated Pregnancy Outcomes in Maternal
      Infant Dyads between a Nigerian and a United States Population.
AB  - Oxidative stress is associated with adverse pregnancy outcomes, and vitamin E has
      powerful anti-oxidant properties with the potential to impact health outcomes.
      Tocopherol isomers of vitamin E differ in their ability to modulate inflammation
      and vary in concentration in diets containing high proportions of processed
      versus unprocessed foods. The purpose of this study was to compare vitamin E
      status and associated pregnancy outcomes (mode of delivery, chorioamnionitis,
      APGARs (measure of appearance, pulse, grimace, activity, respiration),
      gestational age at delivery, and fetal growth) between maternal-infant dyads in a
      developed and a developing nation to identify potentially modifiable differences
      that may impact pregnancy and neonatal outcomes and provide a way to improve
      maternal and neonatal health. Plasma tocopherol levels were evaluated in 189
      Midwestern United States (US) mother-infant pairs and 99 Central Nigerian mother
      infant pairs. Maternal and infant concentrations of alpha-, gamma-, and delta
      tocopherol were measured using HPLC with diode-array detection. Descriptive
      statistics were calculated and tocopherol concentrations were associated with
      clinical outcomes such as mode of delivery, chorioamnionitis, APGARS, and fetal
      growth. Alpha- and gamma-tocopherol levels were higher in the US mothers, (alpha:
      12,357.9 (175.23-34,687.75) vs. 8333.1 (1576.59-16,248.40) (mcg/L); p < 0.001)
      (gamma: 340.7 (224.59-4385.95) vs. 357.5 (66.36-1775.31) (mcg/L); p < 0.001),
      while delta-tocopherol levels were higher in the Nigerian mothers (delta: 261.7
      (24.70-1324.71) vs. 368.9 (43.06-1886.47) (mcg/L); p < 0.001). US infants had
      higher gamma-tocopherol levels than Nigerian infants (203.1 (42.53-1953.23) vs.
      113.8 (0.00-823.00) (mcg/L); p < 0.001), while both the Nigerian mothers and
      infants had higher alpha:gamma-tocopherol ratios (8.5 vs. 26.2, and 8.9 vs. 18.8,
      respectively; p < 0.001). Our results in both populations show associations
      between increased circulating gamma-tocopherol and negative outcomes like
      Caesarian sections, in contrast to the associations with positive outcomes such
      as vaginal delivery seen with increased alpha:gamma-tocopherol ratios. Growth was
      positively associated with alpha- and gamma-tocopherols in cord blood in the US
      population, and with cord blood delta-tocopherols in the Nigerian population.
      Tocopherol levels likely impact health outcomes in pregnancy in a complicated
      metabolism across the maternal-fetal axis that appears to be potentially
      influenced by culture and available diet.

PMID- 30223435
TI  - The Antimicrobial Potential of Bacteria Isolated from Honey Samples Produced in
      the Apiaries Located in Pomeranian Voivodeship in Northern Poland.
AB  - The principal objective of this study was to determine whether the honeys
      produced in apiaries located in Pomeranian Voivodeship (Northern Poland) contain
      bacteria producing metabolites with growth inhibition potential against important
      human and animal pathogens. The pathogens included Staphylococcus aurues,
      Staphyloccocus epidermidis, Escherichia coli, Listeria monocytogenes, Pseudomonas
      aeruginosa, and Candida albicans. From 12 samples of honey, 163 strains of
      bacteria were isolated. Activity against reference staphylococci: S. aurues ATCC
      25923; S. aureus ATCC 29213; S. epidermidis 12228 was observed in 33 (20.3%), 38
      (23.3%), and 41 (25.1%) isolates, respectively. High inhibitory activity was also
      found against Listeria monocytogenes ATCC 7644 in 34 strains (20.9%). Activity
      against Candida albicans ATCC 10231 and especially Gram-negative bacteria:
      Pseudomonas aeruginosa ATCC 27857 and Escherichia coli ATCC 25922 was rarely
      observed. Production of metabolites exhibiting activity against the three
      pathogens mentioned above was confirmed for 13 (7.8%), 3 (1.8%), and 2 (1.2%)
      isolates, respectively. Forty-six isolates were selected for further analysis.
      Within this group, metabolites synthesized by 18 producing strains (39.13%)
      inhibited growth of only one of the reference strains of pathogenic
      microorganisms. However, 14 (30.44%), 8 (17.39%), and 6 (13.04%) strains produced
      agents active against three, two, and four pathogens, respectively. Sequencing of
      the 16S rRNA gene revealed that 80.4% of these 46 producing strains belong to the
      genus Bacillus. However, some producing strains belonging to the genus of
      Peanibacillus, Lysinibacillus, Microbacterium, and Staphylococcus were also
      identified. Furthermore, the analysis of the sequences of 16S rRNA, as well as
      RAPD-PCR, exhibited a significant diversity in the strains tested, even in the
      case of bacteria isolated from the same honey (and classified to the same genus,
      usually Bacillus spp.). This observation suggests environmental origin (nectar,
      water, or pollen) of the producing strains. The research carried out confirmed
      that honey produced in Northern Poland is a promising source of strains of
      bacteria producing metabolites with antimicrobial activity.

PMID- 30223434
TI  - Repurposing of Drugs Targeting YAP-TEAD Functions.
AB  - Drug repurposing is a fast and consolidated approach for the research of new
      active compounds bypassing the long streamline of the drug discovery process.
      Several drugs in clinical practice have been reported for modulating the major
      Hippo pathway's terminal effectors, namely YAP (Yes1-associated protein), TAZ
      (transcriptional co-activator with PDZ-binding motif) and TEAD (transcriptional
      enhanced associate domains), which are directly involved in the regulation of
      cell growth and tissue homeostasis. Since this pathway is known to have many
      cross-talking phenomena with cell signaling pathways, many efforts have been made
      to understand its importance in oncology. Moreover, this could be relevant to
      obtain new molecular tools and potential therapeutic assets. In this review, we
      discuss the main mechanisms of action of the best-known compounds, clinically
      approved or investigational drugs, able to cross-talk and modulate the Hippo
      pathway, as an attractive strategy for the discovery of new potential lead
      compounds.

PMID- 30223436
TI  - Structural Features of Amyloid Fibrils Formed from the Full-Length and Truncated
      Forms of Beta-2-Microglobulin Probed by Fluorescent Dye Thioflavin T.
AB  - The persistence of high concentrations of beta-2-microglobulin (beta2M) in the
      blood of patients with acute renal failure leads to the development of the
      dialysis-related amyloidosis. This disease manifests in the deposition of amyloid
      fibrils formed from the various forms of beta2M in the tissues and biological
      fluids of patients. In this paper, the amyloid fibrils formed from the full
      length beta2M (beta2m) and its variants that lack the 6 and 10 N-terminal amino
      acids of the protein polypeptide chain (DeltaN6beta2m and DeltaN10beta2m,
      respectively) were probed by using the fluorescent dye thioflavin T (ThT). For
      this aim, the tested solutions were prepared via the equilibrium microdialysis
      approach. Spectroscopic analysis of the obtained samples allowed us to detect one
      binding mode (type) of ThT interaction with all the studied variants of beta2M
      amyloid fibrils with affinity ~104 M-1. This interaction can be explained by the
      dye molecules incorporation into the grooves that were formed by the amino acids
      side chains of amyloid protofibrils along the long axis of the fibrils. The
      decrease in the affinity and stoichiometry of the dye interaction with beta2M
      fibrils, as well as in the fluorescence quantum yield and lifetime of the bound
      dye upon the shortening of the protein amino acid sequence were shown. The
      observed differences in the ThT-beta2M fibrils binding parameters and
      characteristics of the bound dye allowed to prove not only the difference of the
      DeltaN10beta2m fibrils from other beta2M fibrils (that can be detected visually,
      for example, by transmission electron microscopy (TEM), but also the differences
      between beta2m and DeltaN6beta2m fibrils (that can not be unequivocally confirmed
      by other approaches). These results prove an essential role of N-terminal amino
      acids of the protein in the formation of the beta2M amyloid fibrils. Information
      about amyloidogenic protein sequences can be claimed in the development of ways
      to inhibit beta2M fibrillogenesis for the treatment of dialysis-related
      amyloidosis.

PMID- 30223437
TI  - C-Type Natriuretic Peptide (CNP) Inhibition of Interferon-gamma-Mediated Gene
      Expression in Human Endothelial Cells In Vitro.
AB  - Cardiovascular diseases, including atherosclerosis, now account for more deaths
      in the Western world than from any other cause. Atherosclerosis has a chronic
      inflammatory component involving Th1 pro-inflammatory cytokines such as IFN
      gamma, which is known to induce endothelial cell inflammatory responses. On the
      other hand CNP, which acts via its receptors to elevate intracellular cGMP, is
      produced by endothelium and endocardium and is upregulated in atherosclerosis. It
      is believed to be protective, however its role in vascular inflammation is not
      well understood. The aim of this study was to investigate the effects of CNP on
      human endothelial cell inflammatory responses following IFN-gamma stimulation.
      Human umbilical vein endothelial cells were treated with either IFN-gamma (10
      ng/mL) or CNP (100 nm), or both in combination, followed by analysis by flow
      cytometry for expression of MHC class I and ICAM-1. IFN-gamma significantly
      increased expression of both molecules, which was significantly inhibited by CNP
      or the cGMP donor 8-Bromoguanosine 3',5'-cyclic monophosphate (1 um). CNP also
      reduced IFN-gamma mediated kynurenine generation by the IFN-gamma regulated
      enzyme indoleamine-2,3-deoxygenase (IDO). We conclude that CNP downmodulates IFN
      gamma induced pro-inflammatory gene expression in human endothelial cells via a
      cGMP-mediated pathway. Thus, CNP may have a protective role in vascular
      inflammation and novel therapeutic strategies for CVD based on upregulation of
      endothelial CNP expression could reduce chronic EC inflammation.

PMID- 30223438
TI  - 2-Bromo-4'-methoxychalcone and 2-Iodo-4'-methoxychalcone Prevent Progression of
      Hyperglycemia and Obesity via 5'-Adenosine-Monophosphate-Activated Protein Kinase
      in Diet-Induced Obese Mice.
AB  - Obesity and diabetes are global health-threatening issues. Interestingly, the
      mechanism of these pathologies is quite different among individuals. The
      discovery and development of new categories of medicines from diverse sources are
      urgently needed for preventing and treating diabetes and other metabolic
      disorders. Previously, we reported that chalcones are important for preventing
      biological disorders, such as diabetes. In this study, we demonstrate that the
      synthetic halogen-containing chalcone derivatives 2-bromo-4'-methoxychalcone
      (compound 5) and 2-iodo-4'-methoxychalcone (compound 6) can promote glucose
      consumption and inhibit cellular lipid accumulation via 5'-adenosine
      monophosphate-activated protein kinase (AMPK) activation and acetyl-CoA
      carboxylase 1 (ACC) phosphorylation in 3T3-L1 adipocytes and C2C12 skeletal
      myotubes. In addition, the two compounds significantly prevented body weight gain
      and impaired glucose tolerance, hyperinsulinemia, and insulin resistance, which
      collectively help to delay the progression of hyperglycemia in high-fat-diet
      induced obese C57BL/6 mice. These findings indicate that 2-bromo-4'
      methoxychalcone and 2-iodo-4'-methoxychalcone could act as AMPK activators, and
      may serve as lead compounds for a new class of medicines that target obesity and
      diabetes.

PMID- 30223440
TI  - Comparison of Antibacterial Adhesion When Salivary Pellicle Is Coated on Both
      Poly(2-hydroxyethyl-methacrylate)- and Polyethylene-glycol-methacrylate-grafted
      Poly(methyl methacrylate).
AB  - Although poly(2-hydroxyethyl methacrylate) (pHEMA) and polyethylene glycol
      methacrylate (PEGMA) have been demonstrated to inhibit bacterial adhesion, no
      study has compared antibacterial adhesion when salivary pellicle is coated on
      polymethyl methacrylate (PMMA) grafted with pHEMA and on PMMA grafted with PEGMA.
      In this study, PMMA discs were fabricated from a commercial orthodontic acrylic
      resin system (Ortho-Jet). Attenuated total reflection-Fourier transform infrared
      spectra taken before and after grafting confirmed that pHEMA and PEGMA were
      successfully grafted on PMMA. Contact angle measurements revealed PMMA-pHEMA to
      be the most hydrophilic, followed by PMMA-PEGMA, and then by PMMA. Zeta potential
      analysis revealed the most negative surface charges on PMMA-PEGMA, followed by
      PMMA-pHEMA, and then by PMMA. Confocal laser scanning microscopy showed green
      fluorescence in the background, indicating images that influenced the accuracy of
      the quantification of live bacteria. Both the optical density value measured at
      600 nm and single plate-serial dilution spotting showed that pHEMA was more
      effective than PEGMA against Escherichia coli and Streptococcus mutans, although
      the difference was not significant. Therefore, the grafting of pHEMA and PEGMA
      separately on PMMA is effective against bacterial adhesion, even after the
      grafted PMMA were coated with salivary pellicle. Surface hydrophilicity,
      bactericidality, and Coulomb repulsion between the negatively charged bacteria
      and the grafted surface contributed to the effectiveness.

PMID- 30223441
TI  - Microstructure and Tribological Properties of Laser Forming Repaired 34CrNiMo6
      Steel.
AB  - Laser forming repair (LFR) technology has considerable potential in high strength
      steel structure repair. 34CrNiMo6 steel has been widely used in high-value
      components, and it is imperative to repair these damaged components. In this
      study, two different thicknesses of repaired layers are deposited on the
      34CrNiMo6 wrought substrate with five layers and 20 layers via LFR technology.
      The microstructure, phases, microhardness, and tribological properties are
      analyzed using optical microscopy, scanning electron microscopy, X-ray
      diffraction, Vickers hardness testing, and dry sliding wear testing. These
      results show that the 34CrNiMo6 repaired layers were successfully deposited on
      the substrate. The microstructure of the laser-repaired layers in the five-layer
      sample included bainite and retained austenite. For the 20-layer sample, the
      microstructure in the top of the repaired layers was still bainite and retained
      austenite, whereas that in the bottom of the repaired layers was transformed into
      ferrite and cementite. The average coefficients of friction of repaired layers is
      not significantly different from the substrate. The wear rate of the five LFR
      layers, 20-layer LFR, and substrate samples were 12.89 * 10-6, 15 * 10-6, and
      23.87 * 10-6 mm3/N.m, respectively. The laser forming repaired samples had better
      wear resistance compared to the substrate. The wear mechanism of laser forming
      repaired samples is abrasive wear; whereas that of the substrate is abrasive wear
      and fatigue wear.

PMID- 30223439
TI  - Heartland Virus Epidemiology, Vector Association, and Disease Potential.
AB  - First identified in two Missouri farmers exhibiting low white-blood-cell and
      platelet counts in 2009, Heartland virus (HRTV) is genetically closely related to
      severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne
      phlebovirus producing similar symptoms in China, Korea, and Japan. Field
      isolations of HRTV from several life stages of unfed, host-seeking Amblyomma
      americanum, the lone star tick, implicated it as a putative vector capable of
      transstadial transmission. Laboratory vector competence assessments confirmed
      transstadial transmission of HRTV, demonstrated vertical infection, and showed co
      feeding infection between A. americanum. A vertical infection rate of 33% from
      adult females to larvae in the laboratory was observed, while only one of 386
      pools of molted nymphs (1930) reared from co-feeding larvae was positive for HRTV
      (maximum-likelihood estimate of infection rate = 0.52/1000). Over 35 human HRTV
      cases, all within the distribution range of A. americanum, have been documented.
      Serological testing of wildlife in areas near the index human cases, as well as
      in widely separated regions of the eastern United States where A. americanum
      occur, indicated many potential hosts such as raccoons and white-tailed deer.
      Attempts, however, to experimentally infect mice, rabbits, hamsters, chickens,
      raccoons, goats, and deer failed to produce detectable viremia. Immune
      compromised mice and hamsters are the only susceptible models. Vertical infection
      augmented by co-feeding transmission could play a role in maintaining the virus
      in nature. A more complete assessment of the natural transmission cycle of HRTV
      coupled with serosurveys and enhanced HRTV disease surveillance are needed to
      better understand transmission dynamics and human health risks.

PMID- 30223444
TI  - Ion Transport Properties and Ionicity of 1,3-Dimethyl-1,2,3-Triazolium Salts with
      Fluorinated Anions.
AB  - 1,2,3-Triazolium salts are an important class of materials with a plethora of
      sophisticated applications. A series of three novel 1,3-dimethyl-1,2,3-triazolium
      salts with fluorine, containing anions of various size, is synthesized by
      methylation of 1,2,3-triazole. Their ion conductivity is measured by impedance
      spectroscopy, and the corresponding ionicities are determined by diffusion
      coefficients obtained from 1H and 19F pulsed field gradient nuclear magnetic
      resonance (PFG NMR) spectroscopy data, revealing that the anion strongly
      influences their ion conductive properties. Since the molar ion conductivities
      and ionicities of the 1,3-dimethyl-1,2,3-triazolium salts are enhanced in
      comparison to other 1,2,3-triazolium salts with longer alkyl substituents, they
      are promising candidates for applications as electrolytes in electrochemical
      devices.

PMID- 30223442
TI  - Melatonin and Its Effects on Plant Systems.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is a nontoxic biological molecule
      produced in a pineal gland of animals and different tissues of plants. It is an
      important secondary messenger molecule, playing a vital role in coping with
      various abiotic and biotic stresses. Melatonin serves as an antioxidant in
      postharvest technology and enhances the postharvest life of fruits and
      vegetables. The application of exogenous melatonin alleviated reactive oxygen
      species and cell damage induced by abiotic and biotic stresses by means of
      repairing mitochondria. Additionally, the regulation of stress-specific genes and
      the activation of pathogenesis-related protein and antioxidant enzymes genes
      under biotic and abiotic stress makes it a more versatile molecule. Besides that,
      the crosstalk with other phytohormones makes inroads to utilize melatonin against
      non-testified stress conditions, such as viruses and nematodes. Furthermore,
      different strategies have been discussed to induce endogenous melatonin activity
      in order to sustain a plant system. Our review highlighted the diverse roles of
      melatonin in a plant system, which could be useful in enhancing the environmental
      friendly crop production and ensure food safety.

PMID- 30223443
TI  - Selected Psychological Aspects of Meat Consumption-A Short Review.
AB  - Eating meat is deeply entrenched in Western culture. It is often associated with
      wealth and a highly nutritional diet; and for many people it is also an
      established habit that is difficult to change. The second half of the 20th
      century was a period of rapid growth in meat consumption, which resulted in
      intensified meat production. At the same time, eating meat has recently become
      subject to criticism for health-related, environmental or humanitarian reasons.
      This review aims to signal the potential consequences of a change of diet or
      switching to diets that are rich/poor in certain ingredients on the functioning
      of the hormonal and nervous system, which translates into changes in mood and
      behavior. This paper discusses the psychological phenomena which underlie the
      difficulty of changing one's food preferences and problems encountered while
      adding new products to the daily diet. Finally, this study summarizes the
      limitations of modifying eating habits that have resulted from established
      attitudes and habits.

PMID- 30223445
TI  - Thickness-Dependent Differential Reflectance Spectra of Monolayer and Few-Layer
      MoS2, MoSe2, WS2 and WSe2.
AB  - The research field of two dimensional (2D) materials strongly relies on optical
      microscopy characterization tools to identify atomically thin materials and to
      determine their number of layers. Moreover, optical microscopy-based techniques
      opened the door to study the optical properties of these nanomaterials. We
      presented a comprehensive study of the differential reflectance spectra of 2D
      semiconducting transition metal dichalcogenides (TMDCs), MoS2, MoSe2, WS2, and
      WSe2, with thickness ranging from one layer up to six layers. We analyzed the
      thickness-dependent energy of the different excitonic features, indicating the
      change in the band structure of the different TMDC materials with the number of
      layers. Our work provided a route to employ differential reflectance spectroscopy
      for determining the number of layers of MoS2, MoSe2, WS2, and WSe2.

PMID- 30223446
TI  - Oleic Acid Nanovesicles of Minoxidil for Enhanced Follicular Delivery.
AB  - Current topical minoxidil (MXD) formulations involve an unpleasant organic
      solvent which causes patient incompliance in addition to side effects in some
      cases. Therefore, the objective of this work was to develop an MXD formulation
      providing enhanced follicular delivery and reduced side effects. Oleic acid,
      being a safer material, was utilized to prepare the nanovesicles, which were
      characterized for size, entrapment efficiency, polydispersity index (PDI), zeta
      potential, and morphology. The nanovesicles were incorporated into the emugel
      Sepineo(r) P 600 (2% w/v) to provide better longer contact time with the scalp
      and improve physical stability. The formulation was evaluated for in vitro drug
      release, ex vivo drug permeation, and drug deposition studies. Follicular
      deposition of the vesicles was also evaluated using a differential tape stripping
      technique and elucidated using confocal microscopy. The optimum oleic acid
      vesicles measured particle size was 317 +/- 4 nm, with high entrapment efficiency
      (69.08 +/- 3.07%), narrow PDI (0.203 +/- 0.01), and a negative zeta potential of 
      13.97 +/- 0.451. The in vitro drug release showed the sustained release of MXD
      from vesicular gel. The skin permeation and deposition studies revealed
      superiority of the prepared MXD vesicular gel (0.2%) in terms of MXD deposition
      in the stratum corneum (SC) and remaining skin over MXD lotion (2%), with
      enhancement ratios of 3.0 and 4.0, respectively. The follicular deposition of MXD
      was 10-fold higher for vesicular gel than the control. Confocal microscopy also
      confirmed the higher absorption of rhodamine via vesicular gel into hair
      follicles as compared to the control. Overall, the current findings demonstrate
      the potential of oleic acid vesicles for effective targeted skin and follicular
      delivery of MXD.

PMID- 30223447
TI  - Vitamin D3 Supplementation Reduces the Symptoms of Upper Respiratory Tract
      Infection during Winter Training in Vitamin D-Insufficient Taekwondo Athletes: A
      Randomized Controlled Trial.
AB  - Vitamin D insufficiency may be associated with increased risk of upper
      respiratory tract infection (URTI) in athletes. This study examined the effects
      of vitamin D3 supplementation on salivary immune functions and symptoms of URTI
      in vitamin D-insufficient taekwondo athletes. Twenty-five male taekwondo
      athletes, aged 19-22 years with vitamin D insufficiency [serum 25-hydroxyvitamin
      D concentrations (25(OH)D, 31.3 +/- 1.39 nmol/L)], participated in this study.
      They were randomized to receive 5000 IU/day of vitamin D3 (n = 13) or placebo
      capsule (n = 12) during 4 weeks of winter training. Blood samples were collected
      two times (pre- and post-tests) for analyzing serum 25(OH)D concentration while
      salivary samples were obtained three times (pre-, mid-, and post-tests) for
      secretory immunoglobulin A (SIgA) and lactoferrin analyses. The symptoms of URTI
      were reported daily during the intervention. Serum 25(OH)D concentration
      significantly increased by 255.6% in the vitamin D group, whereas in the placebo
      group it did not change (p < 0.001). While the significant increase in SIgA was
      observed in both groups (p < 0.001), elevated salivary lactoferrin level in
      response to winter training was found only in the placebo group (p = 0.011). The
      change in serum 25(OH)D concentration was negatively associated with total URTI
      symptoms (r = -0.435, p = 0.015). Vitamin D3 supplementation may be effective in
      reducing the symptoms of URTI during winter training in vitamin D-insufficient
      taekwondo athletes.

PMID- 30223449
TI  - Occupational Health and Safety Vulnerability of Recent Immigrants and Refugees.
AB  - Recent immigrants and refugees have higher rates of work-related injuries and
      illnesses compared to Canadian-born workers. As a result, they are often labelled
      as vulnerable workers. This study explored the factors that contribute to
      occupational health and safety (OHS) vulnerability of recent immigrants and
      refugees with a focus on modifiable factors such as exposure to hazards and
      access to workplace protections, awareness of OHS and worker rights, and
      empowerment to act on those rights. Eighteen focus groups were conducted with 110
      recent immigrants and refugees about their experiences looking for work and in
      their first jobs in Canada. A thematic content analysis was used to organize the
      data and to identify and report themes. The jobs described by participants
      typically involved poor working conditions and exposure to hazards without
      adequate workplace protections. Most participants had limited knowledge of OHS
      and employment rights and tended to not voice safety concerns to employers.
      Understanding OHS vulnerability from the lens of workplace context can help
      identify modifiable conditions that affect the risk of injury and illness among
      recent immigrants and refugees. Safe work integration depends on providing these
      workers with information about their rights, adequate job training, and
      opportunities for participating in injury prevention.

PMID- 30223450
TI  - Multi-Parameter Sensing Device to Detect Liquid Layers Using Long-Period Fiber
      Gratings.
AB  - Insoluble liquids show layers such as water and oil. The detection of the exact
      interface locations and the level changes for layered liquids are of paramount
      importance for chemistry purifications, liquid storage in reservoirs, oil
      transportation, and chemical engineering. However, accurately measuring liquid
      layers is challenging. This paper introduces a multi-parameter sensing device
      based on a long-period fiber grating (LPFG) sensor simultaneously detecting
      boundary and level changes of layered liquids. Laboratory experiments
      demonstrated that the sensor device would respond to the liquid interface change
      as a sharp and sudden resonant wavelength change, while it would show a gradual
      and steady resonant wavelength change to the level changes of layered liquids.
      The lab experiments also showed that the sensor device has a higher sensitivity
      when a higher LPFG cladding mode is used.

PMID- 30223448
TI  - Cathelicidins: Immunomodulatory Antimicrobials.
AB  - Cathelicidins are host defense peptides with antimicrobial and immunomodulatory
      functions. These effector molecules of the innate immune system of many
      vertebrates are diverse in their amino acid sequence but share physicochemical
      characteristics like positive charge and amphipathicity. Besides being
      antimicrobial, cathelicidins have a wide variety in immunomodulatory functions,
      both boosting and inhibiting inflammation, directing chemotaxis, and effecting
      cell differentiation, primarily towards type 1 immune responses. In this review,
      we will examine the biology and various functions of cathelicidins, focusing on
      putting in vitro results in the context of in vivo situations. The pro
      inflammatory and anti-inflammatory functions are highlighted, as well both direct
      and indirect effects on chemotaxis and cell differentiation. Additionally, we
      will discuss the potential and limitations of using cathelicidins as
      immunomodulatory or antimicrobial drugs.

PMID- 30223453
TI  - Thermochromic and Femtosecond-Laser-Induced Damage Performance of Tungsten-Doped
      Vanadium Dioxide Films Prepared Using an Alloy Target.
AB  - Thermochromic tungsten-doped VO2 thin films were successfully fabricated using a
      W-V alloy target. X-ray diffraction analyses showed that the W-doped VO2 film had
      a preferred orientation of (011), and that the doping did not degrade the film
      crystallinity compared with that of the pure film. X-ray photoelectron
      spectroscopy and energy-dispersive spectroscopy showed that the doped 0.81 atom%
      tungsten replaced vanadium in the lattice of the film. The metal-insulator
      transition temperature of the W-doped VO2 film was reduced to 35.5  degrees C,
      which is close to room temperature. Additionally, the infrared transmittance
      modulation of the W-doped film at lambda = 2500 nm reached 56%, indicating an
      excellent switching efficiency. The damage behavior of the W-doped VO2 film under
      a femtosecond-laser irradiation was experimentally investigated. Our results
      revealed that defect-related damages induced by the femtosecond laser are
      relevant for W-doped VO2 films. This study provides valuable insights into VO2
      films for potential applications in laser protection.

PMID- 30223451
TI  - A Plant-Based High-Carbohydrate, Low-Fat Diet in Overweight Individuals in a 16
      Week Randomized Clinical Trial: The Role of Carbohydrates.
AB  - The effects of carbohydrates on body weight and insulin sensitivity are
      controversial. In this 16-week randomized clinical trial, we tested the role of a
      low-fat, plant-based diet on body weight, body composition and insulin
      resistance. As a part of this trial, we investigated the role of changes in
      carbohydrate intake on body composition and insulin resistance. Participants (n =
      75) were randomized to follow a plant-based high-carbohydrate, low-fat (vegan)
      diet (n = 38) or to maintain their current diet (n = 37). Dual-energy X-ray
      absorptiometry was used to measure body composition. Insulin resistance was
      assessed with the Homeostasis Model Assessment (HOMA-IR) index. A repeated
      measure ANOVA model was used to test the between-group differences from baseline
      to 16 weeks. A linear regression model was used to test the relationship between
      carbohydrate intake, and body composition and insulin resistance. Weight
      decreased significantly in the vegan group (treatment effect -6.5 [95% CI -8.9 to
      -4.1] kg; Gxt, p < 0.001). Fat mass was reduced in the vegan group (treatment
      effect -4.3 [95% CI -5.4 to -3.2] kg; Gxt, p < 0.001). HOMA-IR was reduced
      significantly in the vegan group (treatment effect -1.0 [95% CI -1.2 to -0.8];
      Gxt, p = 0.004). Changes in consumption of carbohydrate, as a percentage of
      energy, correlated negatively with changes in BMI (r = -0.53, p < 0.001), fat
      mass (r = -0.55, p < 0.001), volume of visceral fat (r = -0.35, p = 0.006), and
      HOMA (r = -0.27, p = 0.04). These associations remained significant after
      adjustment for energy intake. Changes in consumption of total and insoluble fiber
      correlated negatively with changes in BMI (r = -0.43, p < 0.001; and r = -0.46, p
      < 0.001, respectively), fat mass (r = -0.42, p < 0.001; and r = -0.46, p < 0.001,
      respectively), and volume of visceral fat (r = -0.29, p = 0.03; and r = -0.32, p
      = 0.01, respectively). The associations between total and insoluble fiber and
      changes in BMI and fat mass remained significant even after adjustment for energy
      intake. Increased carbohydrate and fiber intake, as part of a plant-based high
      carbohydrate, low-fat diet, are associated with beneficial effects on weight,
      body composition, and insulin resistance.

PMID- 30223452
TI  - Treatment of Sewage Using a Constructed Soil Rapid Infiltration System Combined
      with Pre-Denitrification.
AB  - The activated sludge process of the anaerobic/oxic (A/O) process has a good
      denitrification performance because it can make full use of the carbon source in
      the original sewage, and the denitrification can provide alkalinity for aerobic
      nitrification. The traditional constructed soil rapid infiltration (CSRI) system,
      on the other hand, has a poor nitrogen removal effect. Dividing the traditional
      CSRI system into two sections, one performs denitrification as an anoxic section,
      while the other performs nitrification as an aerobic section and is placed after
      the anoxic section. The nitrification liquid of the effluent from the aerobic
      section is mixed with the original wastewater and enters the anoxic section for
      denitrification. We expected that this would be improved by combining CSRI with a
      pre-denitrification step that would make full use of the carbon source in the
      original sewage. In a small-scale experimental model, the removal efficiencies of
      nitrogen, in the form of ammonium, nitrate, and total nitrogen (TN), as well as
      chemical oxygen demand (COD), were determined. The hydraulic load was varied,
      while the backflow reflux capacity was kept constant, to determine the effect on
      the pre-denitrification process. An average removal rate of 95.4% for NH4+-N and
      96% for COD could be obtained when a hydraulic load of 80 cm3(cm2.d)-1 and a
      reflux ratio of 75% were applied. Under these conditions, the average removal
      rate of TN was 77.4%, which is much higher than what can be typically achieved
      with conventional CSRI systems.

PMID- 30223455
TI  - Monthly Variations in Perfluorinated Compound Concentrations in Groundwater.
AB  - Large-scale manufacturing of poly- and perfluorinated compounds in the second
      half of the 20th century has led to their ubiquity in the environment, and their
      unique structure has made them persistent contaminants. A recent drinking water
      advisory level issued by the United States Environmental Protection Agency
      lowered the advisory level concentration of perfluorooctanesulfonic acid (PFOS)
      and perfluorooctanoic acid (PFOA) from 200 nanograms per liter and 400 nanograms
      per liter, respectively, to 70 nanograms per liter separately or combined. Small
      temporal variations in PFOS and PFOA concentrations could be the difference
      between meeting or exceeding the recommended limit. In this study, newly sampled
      data from a contaminated military site in Alaska and historical data from former
      Pease Air Force Base were collected. Data were evaluated to determine if monthly
      variations within PFOS and PFOA existed. No statistically significant temporal
      trend was observed in the Alaska data, while the results from Pease, although
      statistically significant, showed the spread of observed contaminant
      concentrations around the fitted line is broad (as indicated by the low R2
      values), indicating that collection date has little value in predicting
      contaminant concentrations. Though not currently the subject of a US EPA health
      advisory, data on perfluorobutanesulfonic acid (PFBS), perfluorohexane sulfonic
      acid (PFHxS), perfluoroheptanoic acid (PFHpA), and perfluorononanoic acid (PFNA)
      were collected for each site and their average concentrations evaluated.

PMID- 30223454
TI  - Relationship between Altered miRNA Expression and DNA Methylation of the DLK1
      DIO3 Region in Azacitidine-Treated Patients with Myelodysplastic Syndromes and
      Acute Myeloid Leukemia with Myelodysplasia-Related Changes.
AB  - The DLK1-DIO3 region contains a large miRNA cluster, the overexpression of which
      has previously been associated with myelodysplastic syndromes (MDS). To reveal
      whether this overexpression is epigenetically regulated, we performed an
      integrative analysis of miRNA/mRNA expression and DNA methylation of the
      regulatory sequences in the region (promoter of the MEG3 gene) in CD34+ bone
      marrow cells from the patients with higher-risk MDS and acute myeloid leukemia
      with myelodysplasia-related changes (AML-MRC), before and during hypomethylating
      therapy with azacytidine (AZA). Before treatment, 50% of patients showed
      significant miRNA/mRNA overexpression in conjunction with a diagnosis of AML-MRC.
      Importantly, increased level of MEG3 was associated with poor outcome. After AZA
      treatment, the expression levels were reduced and were closer to those seen in
      the healthy controls. In half of the patients, we observed significant
      hypermethylation in a region preceding the MEG3 gene that negatively correlated
      with expression. Interestingly, this hypermethylation (when found before
      treatment) was associated with longer progression-free survival after therapy
      initiation. However, neither expression nor methylation status were associated
      with future responsiveness to AZA treatment. In conclusion, we correlated
      expression and methylation changes in the DLK1-DIO3 region, and we propose a
      complex model for regulation of this region in myelodysplasia.

PMID- 30223456
TI  - Effect of Lachancea thermotolerans on the Formation of Polymeric Pigments during
      Sequential Fermentation with Schizosaccharosmyces pombe and Saccharomyces
      cerevisiae.
AB  - Anthocyanins in red grape musts may evolve during the winemaking process and wine
      aging for several different reasons; colour stability and evolution is a complex
      process that may depend on grape variety, winemaking technology, fermentative
      yeast selection, co-pigmentation phenomena and polymerization. The condensation
      of flavanols with anthocyanins may occur either with the flavylium ion or with
      the hemiacetal formation in order to produce oligomers and polymers. The kinetics
      of the reaction are enhanced by the presence of metabolic acetaldehyde, promoting
      the formation of pyranoanthocyanin-type dimers or flavanol-ethyl-anthocyanin
      structures. The experimental design carried out using white must corrected with
      the addition of malvidin-3-O-glucoside and flavanols, suggests that non
      Saccharomyces yeasts are able to provide increased levels of colour intensity and
      larger polymeric pigment ratios and polymerization indexes. The selection of non
      Saccharomyces genera, in particular Lachancea thermotolerans and
      Schizosaccharomyces pombe in sequential fermentation, have provided experimental
      wines with increased fruity esters, as well as producing wines with potential
      pigment compositions, even though there is an important reduction of total
      anthocyanins.

PMID- 30223457
TI  - Novel Alkylimidazolium Ionic Liquids as an Antibacterial Alternative to Pathogens
      of the Skin and Soft Tissue Infections.
AB  - Keeping in mind the concept of green chemistry, this research aims to synthesize
      and characterize new ionic liquids (ILs) derived from N-cinnamyl imidazole with
      different sizes of alkyl chains (1, 6, 8, and 10 carbon atoms), and evaluate
      their antibacterial activity against Skin and soft tissue infections (SSTIs)
      causative bacteria. The antibacterial screening was carried out by agar well
      diffusion and the Minimum Inhibitory Concentration (MIC) and Half Maximum
      Inhibitory Concentration (IC50) of the different ILs were determined by
      microdilution in broth, also Molecular dynamics simulations were performed to
      study the interaction mechanism between ILs and membranes. The MIC value in Gram
      positive bacteria showed that as the hydrocarbon chain increases, the MIC value
      decreases with a dose-dependent effect. Furthermore, Gram-negative bacteria
      showed high MIC values, which were also evidenced in the antibacterial screening.
      The molecular dynamics showed an incorporation of the ILs with the longer chain
      (10 C), corresponding to a passive diffusion towards the membrane surface, for
      its part, the ILs with the shorter chain due to its lack of hydrophobicity was
      not incorporated into the bilayer. Finally, the new ILs synthesized could be an
      alternative for the treatment of Gram-positive bacteria causative of SSTIs.

PMID- 30223458
TI  - Exploring Peptide-Solvent Interactions: A Computational Study.
AB  - The dilemma of reconciling the contradictory evidence regarding the conformation
      of long solvated peptide chains is the so-called "reconciliation problem". Clues
      regarding the stability of certain conformations likely lie in the electronic
      structure at the peptide-solvent interface, but the peptide-solvent interaction
      is not fully understood. Here, we study the influence of aqueous solvent on
      peptide conformations by using classical molecular dynamics (MD) and quantum
      mechanical/molecular mechanical (QM/MM) energy calculations. The model systems
      include an 11-residue peptide, X 2 A 7 O 2 (XAO), where X, A, and O denote
      diaminobutyric acid, alanine, and ornithine, respectively, and a 9-mer (Arg-Pro
      Pro-Gly-Phe-Ser-Ala-Phe-Lys). Spectroscopic and MD data present conflicting
      evidence regarding the structure of XAO in water; some results indicate that XAO
      adopts a polyproline II (P II ) conformation, whereas other findings suggest that
      XAO explores a range of conformations. To investigate this contradiction, we
      present here the results of MD simulations of XAO and the 9-mer in aqueous
      solution, combined with QM/MM energy calculations.

PMID- 30223459
TI  - Fabrication and Characterization of a High-Performance Multi-Annular
      Backscattered Electron Detector for Desktop SEM.
AB  - Scanning electron microscopy has been developed for topographic analysis at the
      nanometer scale. Herein, we present a silicon p-n diode with multi-annular
      configuration to detect backscattering electrons (BSE) in a homemade desktop
      scanning electron microscope (SEM). The multi-annular configuration enables the
      enhancement of the topography contrast of 82.11 nA/MUm as compared with the
      commercial multi-fan-shaped BSE detector of 40.08 nA/MUm. Additionally, we
      integrated it with lateral p-n junction processing and aluminum grid structure to
      increase the sensitivity and efficiency of the multi-annular BSE detector that
      gives higher sensitivity of atomic number contrast and better surface topography
      contrast of BSE images for low-energy detection. The responsivity data also shows
      that MA-AL and MA p-n detectors have higher gain value than the MA detector does.
      The standard deviation of measurements is no higher than 1%. These results verify
      that MA p-n and MA-AL detectors are stable and can function well in SEM for low
      energy applications. It is demonstrated that the multi-annular (MA) detectors are
      well suited for imaging in SEM systems.

PMID- 30223461
TI  - Optimization-Based Wi-Fi Radio Map Construction for Indoor Positioning Using Only
      Smart Phones.
AB  - Fingerprinting-based Wi-Fi indoor positioning has great potential for positioning
      in GPS-denied areas. However, establishing a fingerprinting map (also called a
      radio map) prior to positioning (site survey) is normally a labor-intensive task.
      This paper proposes a method for easy site survey without need for any extra
      hardware. The user can conduct the site survey adopting only a smart phone. The
      collected inertial-based readings are processed using the pedestrian dead
      reckoning algorithms to generate a raw trajectory. Then a factor graph
      optimization method is proposed to re-estimate the trajectory by adding
      constraints originated from collected Wi-Fi fingerprints and landmark positions.
      The proposed method is verified through an experiment in a mall. The mean
      positioning error is 1.10 m and the maximum error is 2.25 m. This level of
      positioning accuracy is considered sufficient for radio map generation purposes.
      A classical baseline algorithm, the k-Nearest Neighbor (kNN) algorithm, is
      adopted to test the positioning performance of the radio map (RM), which also
      validates the quality of the constructed RM from the proposed method.

PMID- 30223460
TI  - Surveying Alcohol Outlet Density in Four Neighborhoods of Beirut Lebanon:
      Implications for Future Research and National Policy.
AB  - Underage drinking among youth in Lebanon is increasing. Regulating availability
      is one of the best buy policies recommended by the World Health Organization. To
      quantitatively document the current status of alcohol availability to youth in
      Lebanon, we used GPS technology to survey alcohol outlet density in four highly
      populated neighborhoods in Beirut, Lebanon, and to estimate their proximity to
      educational institutions. The density of alcohol outlets ranged from 18.30 to
      80.95 per km2 (average of 39.6 alcohol outlets/km2). The highest number of total
      alcohol outlets was in the "Hamra & Jamiaa" area, which includes one of the
      largest private universities in the country. Thirteen out of 109 (12%) alcohol
      outlets (on and off-premise) were located less 100 m away from educational
      institutions, in violation of the current licensing law. None of the off-premise
      and the majority (94%) of on-premise alcohol outlets displayed the "no sale for
      <18" sign. Findings were indicative of an environment conducive to increased
      access and availability of alcohol among youth in Lebanon probably attributed to
      the prevailing weak alcohol policies and their enforcement. Systematic collection
      and reporting of alcohol outlet densities is critical to understand the alcogenic
      environment and guide local harm reduction policies.

PMID- 30223462
TI  - Dual Light- and pH-Responsive Composite of Polyazo-Derivative Grafted Cellulose
      Nanocrystals.
AB  - As a type of functional group, azo-derivatives are commonly used to synthesize
      responsive materials. Cellulose nanocrystals (CNCs), prepared by acid hydrolysis
      of cotton, were dewatered and reacted with 2-bromoisobuturyl bromide to form a
      macro-initiator, which grafted 6-[4-(4-methoxyphenyl-azo) phenoxy] hexyl
      methacrylate (MMAZO) via atom transfer radical polymerization. The successful
      grafting was supported by Fourier transform infrared spectroscopy (FT-IR) and
      Solid magnetic resonance carbon spectrum (MAS 13C-NMR). The morphology and
      surface composition of the poly{6-[4-(4-methoxyphenylazo) phenoxy] hexyl
      methacrylate} (PMMAZO)-grafted CNCs were confirmed with Transmission electron
      microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). The grafting rate on
      the macro-initiator of CNCs was over 870%, and the polydispersities of branched
      polymers were narrow. The crystal structure of CNCs did not change after
      grafting, as determined by X-ray diffraction (XRD). The polymer PMMAZO improved
      the thermal stability of cellulose nanocrystals, as shown by thermogravimetry
      analysis (TGA). Then the PMMAZO-grafted CNCs were mixed with polyurethane and
      casted to form a composite film. The film showed a significant light and pH
      response, which may be suitable for visual acid-alkali measurement and reversible
      optical storage.

PMID- 30223463
TI  - Individualized Transcriptional Resolution of Complicated Malaria in a Colombian
      Study.
AB  - To evaluate whether recovery from complicated malaria follows a common trajectory
      in terms of immunological mechanism or, rather, is highly individualized for each
      patient, we performed longitudinal gene expression profiling of whole blood. RNA
      sequencing (RNAseq) was performed on blood samples obtained from eight patients
      on four consecutive days between hospital admission and discharge. Six patients
      were infected with Plasmodium falciparum, and two with Plasmodium vivax; one
      patient was a pregnant woman infected with P. falciparum, who was hospitalized
      for several weeks. The characterization of blood transcript modules (BTM) and
      blood informative transcripts (BIT) revealed that patients' responses showed
      little commonality, being dominated by the balance of gene activity relating to
      lymphocyte function, inflammation, and interferon responses specific to each
      patient. Only weak correlations with specific complicated malaria symptoms such
      as jaundice, thrombocytopenia, or anemia were observed. The differential
      expression of individual genes, including transcripts derived from the human
      leukocyte antigen (HLA) complex, generally reflected differences in the
      underlying immune processes. Although the results of this pilot study do not
      point to any single process that might provide a target for complicated malaria
      treatment or prevention or personalized medical strategies, larger patient series
      and more extensive blood sampling may allow the classification of patients
      according to their type of response in order to develop novel therapeutic
      approaches.

PMID- 30223464
TI  - Network Distance-Based Simulated Annealing and Fuzzy Clustering for Sensor
      Placement Ensuring Observability and Minimal Relative Degree.
AB  - Network science-based analysis of the observability of dynamical systems has been
      a focus of attention over the past five years. The maximum matching-based
      approach provides a simple tool to determine the minimum number of sensors and
      their positions. However, the resulting proportion of sensors is particularly
      small when compared to the size of the system, and, although structural
      observability is ensured, the system demands additional sensors to provide the
      small relative order needed for fast and robust process monitoring and control.
      In this paper, two clustering and simulated annealing-based methodologies are
      proposed to assign additional sensors to the dynamical systems. The proposed
      methodologies simplify the observation of the system and decrease its relative
      order. The usefulness of the proposed method is justified in a sensor-placement
      problem of a heat exchanger network. The results show that the relative order of
      the observability is decreased significantly by an increase in the number of
      additional sensors.

PMID- 30223467
TI  - Relationship between Sleep and Psychosis in the Pediatric Population: A Brief
      Review.
AB  - Sleep disorders are common in several psychiatric disorders, including
      schizophrenia. In the pediatric population, the relationship between sleep and
      psychosis is not completely understood due to limited research studies
      investigating the link. Insomnia is noted to be a predictor of psychosis,
      especially in ultrahigh risk adolescents. Sleep difficulties are also associated
      with a two to three-fold increase in paranoid thinking. Biological factors, such
      as decrease in thalamic volume, have been observed in children with schizophrenia
      and ultrahigh risk adolescents with associated sleep impairment. Objective
      studies have indicated possible actigraphy base measures to be the predictor of
      psychosis after a one year follow-up. The studies using polysomnography have rare
      and inconsistent results. In this brief review, we provide an overview of
      existing literature. We also posit that future research will be beneficial in
      understanding the initiation, course and progression of sleep disturbance in the
      high risk pediatric population with the goal of implementing interventions to
      alter the development of psychosis.

PMID- 30223466
TI  - Sport Courage, Worry and Fear in Relation to Success of Alpine Ski Learning.
AB  - (1) Background: Individuals' psychological traits can influence not just success
      in sport but also the ability to learn new motor skills. We investigated whether
      sport courage, worry and fear differ between alpine ski-naive and basic level
      skiers and how they affect ski learning. (2): A total of 337 students (249 ski
      naive and 88 basic level) participated in research consisting of a four-part
      questionnaire and structured skiing program. (3) Results: For beginners, lower
      fear (r = -0.30, p < 0.01) and higher Self-efficiency (r = 0.28, p < 0.05) and
      mastery (r = 0.20, p < 0.01) were associated with better performance; reducing
      fear and increasing self-efficiency and worry increased performance. Experienced
      skiers were better in determination, mastery, and self-efficiency (all p < 0.05).
      In case of lower score in worry (r = -0.28, p < 0.01) and higher in self
      efficiency (r = 0.22, p < 0.05) performance was better. Males scored higher in
      sport courage scale-31 (all p < 0.05). In particular, self-efficiency was
      associated with better (r = 0.39, p < 0.01), and higher fear with poorer
      performance (r = -0.33, p < 0.01). Moreover, self-efficiency was a predictor of
      ski success (p < 0.001). On the other hand, females like ski beginners scored
      higher in fear (p < 0.001). In females, determination, mastery and self
      efficiency had a positive correlation with skiing (r = 0.21, p < 0.05, r = 0.28,
      p < 0.01, and r = 0.33, p < 0.01, respectively), while association between Fear
      and skiing (r = -0.46, p < 0.01) was negative, and fear (p < 0.001) was inversely
      related to success. (4): Conclusions: Psychological factors and gender
      differences need to be considered during learning phases of alpine skiing. There
      is a positive association between self-efficiency and performance of male ski
      beginners, and negative association between fear and achieved results in basic
      alpine ski school in case of female ski beginners.

PMID- 30223468
TI  - Enamel Anti-Demineralization Effect of Orthodontic Adhesive Containing Bioactive
      Glass and Graphene Oxide: An In-Vitro Study.
AB  - White spot lesions (WSLs), a side effect of orthodontic treatment, can result in
      reversible and unaesthetic results. Graphene oxide (GO) with a bioactive glass
      (BAG) mixture (BAG@GO) was added to Low-Viscosity Transbond XT (LV) in a ratio of
      1, 3, and 5%. The composite's characterization and its physical and biological
      properties were verified with scanning electron microscopy (SEM) and X-ray
      diffraction (XRD); its microhardness, shear bond strength (SBS), cell viability,
      and adhesive remnant index (ARI) were also assessed. Efficiency in reducing WSL
      was evaluated using antibacterial activity of S. mutans. Anti-demineralization
      was analyzed using a cycle of the acid-base solution. Adhesives with 3 wt.% or 5
      wt.% of BAG@GO showed significant increase in microhardness compared with LV. The
      sample and LV groups showed no significant differences in SBS or ARI. The cell
      viability test confirmed that none of the sample groups showed higher toxicity
      compared to the LV group. Antibacterial activity was higher in the 48-h group
      than in the 24 h group; the 48 h test showed that BAG@GO had a high antibacterial
      effect, which was more pronounced in 5 wt.% of BAG@GO. Anti-demineralization
      effect was higher in the BAG@GO-group than in the LV-group; the higher the BAG@GO
      concentration, the higher the anti-demineralization effect.

PMID- 30223465
TI  - TOP2B: The First Thirty Years.
AB  - Type II DNA topoisomerases (EC 5.99.1.3) are enzymes that catalyse topological
      changes in DNA in an ATP dependent manner. Strand passage reactions involve
      passing one double stranded DNA duplex (transported helix) through a transient
      enzyme-bridged break in another (gated helix). This activity is required for a
      range of cellular processes including transcription. Vertebrates have two
      isoforms: topoisomerase IIalpha and beta. Topoisomerase IIbeta was first reported
      in 1987. Here we review the research on DNA topoisomerase IIbeta over the 30
      years since its discovery.

PMID- 30223469
TI  - Innovating New Rural Cooperative Medical Scheme (NCMS) for Better Patient
      Satisfaction in Rural China.
AB  - With the broadening application of the New Rural Cooperative Medical Scheme
      (NCMS), its role in patient satisfaction in rural China has shifted to be the
      focus of academic research. Based on a technology acceptance model, this study
      will investigate the factors and mechanisms influencing patient satisfaction on
      NCMSS in rural places in China. In this study, based on a technology acceptance
      model, we developed a model that is associated with the influencing factors,
      patients' continued participation and patient satisfaction, and conducted an
      empirical analysis based on data collected from rural areas of China's Anhui
      Province. A NCMS's reputed reliability, value, and convenience played a key role
      in positively influencing patient satisfaction. However, long-term patient
      participation was not significantly influenced by other social factors. In order
      to increase patient satisfaction, NCMS policy and implementation procedure needs
      further government modification and innovation with the goal of improving the
      reimbursement ratio, reducing the financial burden, and improving patient
      convenience.

PMID- 30223471
TI  - Optimization of Coconut Fiber in Coconut Shell Concrete and Its Mechanical and
      Bond Properties.
AB  - Coconut shell concrete is one of the recently established lightweight concretes.
      This paper discusses the optimization of adding coconut fibers in both coconut
      shell concrete and conventional concrete. Coconut fibers at different aspect
      ratios of 16.67, 33.33, 50, 66.67, 83.33, and 100 and volume fractions of 1, 2,
      3, 4, and 5% were tried. The maximum compressive strength was attained at an
      aspect ratio of 83.33 and volume fraction of 3% for conventional concrete, and
      aspect ratio 66.67 and volume fraction 3% for coconut shell concrete. Flexural
      strength increased by 30.63% (conventional concrete) and 53.66% (coconut shell
      concrete) on the addition of coconut fibers. Similarly, the split tensile
      strength increased by 19.44% and 30%, respectively. The number of blows needed
      for failure of specimen in impact resistance test was more for concrete mixed
      with fibers. The experimental bond stresses were higher than the theoretical
      values recommended by IS 456: 2000 (Indian Standard) and BS 8110 (British
      Standard). This study shows that the addition of coconut fiber enhances the
      properties of both conventional and coconut shell concrete.

PMID- 30223470
TI  - Proteasome-Rich PaCS as an Oncofetal UPS Structure Handling Cytosolic
      Polyubiquitinated Proteins. In Vivo Occurrence, in Vitro Induction, and
      Biological Role.
AB  - In this article, we outline and discuss available information on the cellular
      site and mechanism of proteasome interaction with cytosolic polyubiquitinated
      proteins and heat-shock molecules. The particulate cytoplasmic structure (PaCS)
      formed by barrel-like particles, closely reproducing in vivo the high-resolution
      structure of 26S proteasome as isolated in vitro, has been detected in a variety
      of fetal and neoplastic cells, from living tissue or cultured cell lines.
      Specific trophic factors and interleukins were found to induce PaCS during in
      vitro differentiation of dendritic, natural killer (NK), or megakaryoblastic
      cells, apparently through activation of the MAPK-ERK pathway. Direct interaction
      of CagA bacterial oncoprotein with proteasome was shown inside the PaCSs of a
      Helicobacter pylori-infected gastric epithelium, a finding suggesting a role for
      PaCS in CagA-mediated gastric carcinogenesis. PaCS dissolution and autophagy were
      seen after withdrawal of inducing factors. PaCS-filled cell blebs and ectosomes
      were found in some cells and may represent a potential intercellular discharge
      and transport system of polyubiquitinated antigenic proteins. PaCS differs
      substantially from the inclusion bodies, sequestosomes, and aggresomes reported
      in proteinopathies like Huntington or Parkinson diseases, which usually lack
      PaCS. The latter seems more linked to conditions of increased cell
      proliferation/differentiation, implying an increased functional demand to the
      ubiquitin-proteasome system.

PMID- 30223474
TI  - Thin Electric Heating Membrane Constructed with a Three-Dimensional
      Nanofibrillated Cellulose-Graphene-Graphene Oxide System.
AB  - Nanofibrillated cellulose (NFC) and graphene oxide (GO) with reinforcing and film
      forming properties were employed with graphene to develop a novel and thin
      electric heating membrane with heat dissipation controllability. A negative
      charge was found on the surface of GO and NFC in aqueous dispersions, which
      contributed to the homogeneous distribution of the graphene sheets. The membrane
      had a good laminated structure with three-dimensional interaction between GO and
      NFC, with embedded graphene sheets. Conductivity was characterized as a function
      of the amount of graphene, thus giving control over to the heating power by
      adjusting the ratio of graphene. Subsequent electric heating tests can remove
      irregularities on the GO and graphene sheet, improving the laminated structure
      further. The temperature on the surface of the membrane presented an exponential
      increasing regularity with time. Under the same power density and time, the
      stabilized temperature rise of membranes was higher when grammage was higher,
      which was characterized by the linear function of the power density. Low-grammage
      membranes (1 and 4 g.m-2) also exhibited regular and even stabilized temperature
      rises. The indicated structure and heating performance of the membrane, as well
      as the variation induced by Joule heating, would drive its applications.

PMID- 30223472
TI  - F13A1 Gene Variant (V34L) and Residual Circulating FXIIIA Levels Predict Short-
      and Long-Term Mortality in Acute Myocardial Infarction after Coronary
      Angioplasty.
AB  - Factor XIIIA (FXIIIA) levels are independent predictors of early prognosis after
      acute myocardial infarction (AMI) and the Valine-to-Leucine (V34L) single
      nucleotide polymorphism (SNP) seems associated with lower AMI risk. Since the
      long-term AMI prognosis merits deeper investigation, we performed an
      observational study evaluating relationships between FXIIIA residual levels,
      cardiovascular risk-factors, and inherited genetic predispositions. FXIIIA V34L
      was genotyped in 333 AMI patients and a five-year follow-up was performed. FXIIIA
      levels assessed at day-zero (d0) and four days after AMI (d4), and conventional
      risk factors were analyzed, focusing on the development of major adverse
      cardiovascular events (MACE). FXIIIA assessed at d0 and d4 was also an
      independent MACE predictor in the long-term follow-up (FXIIIAd0, Odds Ratio (OR)
      = 3.02, 1.79-5.1, p = 0.013; FXIIIAd4, OR = 4.46, 2.33-8.55, p = 0.0001).
      FXIIIAd4 showed the strongest MACE association, suggesting that the FXIIIA
      protective role is maximized when high levels are maintained for longer time.
      Conversely, FXIIIA levels stratified by V34L predicted MACE at a lesser extent
      among L34-carriers (Hazard Risk (HR)VV34 = 3.89, 2.19-6.87, p = 0.000003; HRL34
      carriers = 2.78, 1.39-5.57, p = 0.0039), and V34L did not predict all MACE, only
      multiple-MACE occurrence (p = 0.0087). Finally, in survival analysis, heart
      failure and death differed significantly from stroke and recurrent ischemia (p =
      0.0013), with FXIIIA levels appreciably lower in the former (p = 0.05). Overall,
      genetically-determined FXIIIA levels have a significant long-term prognostic
      role, suggesting that a pharmacogenetics approach might help to select those AMI
      patients at risk of poor prognosis in the need of dedicated treatments.

PMID- 30223473
TI  - Drug Repurposing of Metabolic Agents in Malignant Glioma.
AB  - Gliomas are highly invasive brain tumors with short patient survival. One major
      pathogenic factor is aberrant tumor metabolism, which may be targeted with
      different specific and unspecific agents. Drug repurposing is of increasing
      interest in glioma research. Drugs interfering with the patient's metabolism may
      also influence glioma metabolism. In this review, we outline definitions and
      methods for drug repurposing. Furthermore, we give insights into important
      candidates for a metabolic drug repurposing, namely metformin, statins, non
      steroidal anti-inflammatory drugs, disulfiram and lonidamine. Advantages and
      pitfalls of drug repurposing will finally be discussed.

PMID- 30223476
TI  - Ex Situ Fabrication of Polypyrrole-Coated Core-Shell Nanoparticles for High
      Performance Coin Cell Supercapacitor.
AB  - Silica-conducting polymer (SiO2-CP) has the advantages of high electrical
      conductivity, structural stability, and the facile formation of thin-film. This
      work deals with the preparation and optimization of polypyrrole (PPy)
      encapsulated silica nanoparticles (SiO2 NPs) using an ex situ method. The SiO2
      PPy core-shell NPs prepared by the ex situ method are well dispersed in water and
      facilitate the mass production of thin-film electrodes with improved electrical
      and electrochemical performances using a simple solution process. As-prepared
      SiO2-PPy core-shell NPs with different particle sizes were applied to electrode
      materials for two-electrode supercapacitors based on coin cell batteries. It was
      confirmed that the areal capacitance (73.1 mF/cm2), volumetric capacitance (243.5
      F/cm3), and cycling stability (88.9% after 5000 cycles) of the coin cell
      employing the ex situ core-shell was superior to that of the conventional core
      shell (4.2 mF/cm2, 14.2 mF/cm3, and 82.2%). Considering these facts, the ex situ
      method provides a facile way to produce highly-conductive thin-film electrodes
      with enhanced electrical and electrochemical properties for the coin cell
      supercapacitor application.

PMID- 30223475
TI  - A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination
      Infection Model in the Presence of Maternal Antibodies.
AB  - The antigenically conserved hemagglutinin stalk region is a target for universal
      influenza virus vaccines since antibodies against it can provide broad protection
      against influenza viruses of different subtypes. We tested a universal influenza
      virus vaccination regimen based on sequential immunization with chimeric
      hemagglutinin (HA) containing viruses in a swine influenza virus pig model with
      maternal antibodies against pandemic H1N1. Vaccines were administered as live
      attenuated virus or inactivated influenza virus split vaccine (+/- Emulsigen
      adjuvant). As controls, we included groups that received trivalent inactivated
      influenza vaccine that contained pandemic H1N1 antigens, inactivated adjuvanted
      H1N2 vaccine (control group for vaccine associated enhanced respiratory disease
      in the pig model) or mock-vaccination. No induction of H1 head or stalk-specific
      antibody responses was observed upon vaccination, while responses against H3 and
      influenza B HA were elicited in the group vaccinated with the trivalent vaccine.
      Four weeks post vaccination, pigs were intratracheally challenged with pandemic
      H1N1 virus and euthanized 5 days after challenge. Despite the lack of detectable
      anti-stalk immunity, the chimeric hemagglutinin vaccine resulted in better
      clinical outcomes compared to control groups.

PMID- 30223478
TI  - Recycled Rubber as an Aggregate Replacement in Self-Compacting Concrete
      Literature Overview.
AB  - In the past few decades, due to the exponential increase of the world's
      population, the number of discarded waste tires has become a serious ecological
      and environmental problem. Decomposition of waste tire rubber can take longer
      than 50 years, and every year the number of discarded tires is rapidly growing.
      With the inclusion of waste tire rubber into self-compacting concrete this global
      problem can be reduced. Waste tire rubber can be incorporated in self-compacting
      concrete by partially replacing the natural fine and coarse aggregate, reducing
      consumption of sand and gravel and preserving these natural materials. In
      addition, recycling and reusing waste tire rubber avoids the need for tire
      landfilling, as one of the major ecological problem of the near future.
      Replacement of natural aggregate with waste tire rubber can have an undesirable
      influence on the mechanical properties of self-compacting concrete, i.e.,
      compressive strength, flexural strength, splitting tensile strength, and modulus
      of elasticity, however. On the other hand, replacing natural gravel or sand with
      waste tire rubber can improve impact resistance, ductility, and fatigue
      resistance. This paper presents an overview of the literature investigating
      recycled waste tire rubber used as a fine and/or coarse aggregate replacement in
      self-compacting concrete and its influence on several essential fresh and
      hardened self-compacting concrete properties.

PMID- 30223477
TI  - Food Rating Scale in Food Services: From Development to Assessment of a Strategy
      for Consumer Healthier Choices.
AB  - This study aimed to create an easy tool to identify healthier choices for meal
      assembly in food services (self-service restaurants) and to allow consumers to
      compose their plates to make healthier choices. It is an interventional study,
      and the first step was setting healthy food parameters to design a rating scale.
      The first evaluation criterion was based on energy density (ED) and sodium
      content (SC) using "traffic light" color in the dishes' nameplates; the second
      criterion was based on food groups; the third criterion was based on ingredients
      of the meals. After using the classification, we assessed the rating scale in a
      food service and we evaluated the strategy with its consumers. To evaluate the
      effect of the nutritional intervention, we developed a multiple-choice
      questionnaire with eight questions to measure the impact on consumer food choices
      quantitatively. The dish nameplate allows identification of healthier choices
      regarding SC and/or ED by colors; ingredients that compose the dish; the food
      group and the serving size, helping the identification of the amount of food to
      compose the meal. Banners helped consumers to understand the information. After
      four weeks, all the consumers (n = 1000) received questionnaires regarding their
      comprehension of the classification. The questionnaire presented an ICC of 0.71.
      Most of the preparations (61%) were inadequate based on ED and/or SC at the
      studied food service. A total of 556 consumers returned questionnaires, and 86.3%
      of them observed the rating scale as a nutritional strategy. Almost 55% (n = 261)
      of consumers reported changes in food choice after reading the dishes nameplates.
      The items with greater impact on consumer change in eating behavior were the use
      of colors as an indicator of nutritional quality, portion size information and
      ingredients list. Almost 25% of the consumers that changed their eating behavior
      noticed more than three items presented on the nameplate.

PMID- 30223479
TI  - The Effects of Cold Saponification on the Unsaponified Fatty Acid Composition and
      Sensory Perception of Commercial Natural Herbal Soaps.
AB  - Saponification is the process in which triglycerides are combined with a strong
      base to form fatty acid metal salts during the soap-making process. The
      distribution of unsaturated and saturated fatty acid determines the hardness,
      aroma, cleansing, lather, and moisturizing abilities of soaps. Plant extracts,
      such as rosemary, vegetable, and essential oils are frequently added to soaps to
      enhance quality and sensory appeal. Three natural soaps were formulated using
      cold saponification to produce a base or control bar (BB), hibiscus rosehip bar
      (H), and a forest grove bar (FG). Rosemary extract (R) or essential oil (A)
      blends were added as additives to each formulation prior to curing to evaluate
      the effects of natural plant additives on the lipid composition and sensory
      characteristics of these natural herbal soaps. A total of seven natural soaps,
      three without additives (BB, H, FG) and four with additives (BBR, HA, FGR, FGA),
      were manufactured and studied. The majority (86-99%) of the polyunsaturated fatty
      acids (5.0-7.0 ug/mg) remained unsaponified in the manufactured natural soaps
      regardless of feedstock used. Principal component analysis (PCA) analyses showed
      the unsaponifiable fatty acids were different in the hibiscus bar compared to the
      other bars. There was a very strong correlation between the content of
      unsaponified C18:3n3 and C18:1n9 in all natural soaps. These results indicate
      that unsaponified fatty acids are important contributors to the quality and
      overall sensory perception and preference of natural herbal soaps following
      manufacturing by cold saponification.

PMID- 30223480
TI  - Effects of Tea Catechins on Alzheimer's Disease: Recent Updates and Perspectives.
AB  - Alzheimer's disease (AD) is one of the most common neurodegenerative disorders
      worldwide. Its incidence is gradually increasing because of an aging demographic.
      Therefore, AD prevention and modification is important to improve the health
      status of older adults. Oxidative stress is a component of the pathological
      mechanisms underlying AD. It is caused by a disruption of the balance between
      reactive oxygen species and antioxidant molecules. This imbalance also causes
      neuroinflammation. Catechins, which are bioactive components of tea, have
      antioxidative and anti-inflammatory effects. Moreover, other potential properties
      related to AD prevention and modification have been reported in in vitro and in
      vivo studies. Several clinical studies have also been conducted to date. The
      current review summarizes recent updates and perspectives of the effects of
      catechins on AD based on the molecular mechanisms and related clinical studies.

PMID- 30223481
TI  - Proteogenomic Identification of a Novel Protein-Encoding Gene in Bovine
      Herpesvirus 1 That Is Expressed during Productive Infection.
AB  - Bovine herpesvirus 1 (BoHV-1) is one of several microbes that contributes to the
      development of the bovine respiratory disease (BRD) and can also induce abortions
      in cattle. As other alpha-herpesvirinae subfamily members, BoHV-1 efficiently
      replicates in many cell types and subsequently establishes a life-long latent
      infection in sensory neurons. BoHV-1 encodes more than 70 proteins that are
      expressed in a well-defined manner during productive infection. However, in
      silico open reading frame (ORF) prediction of the BoHV-1 genome suggests that the
      virus may encode more than one hundred proteins. In this study we used mass
      spectrometry followed by proteogenomic mapping to reveal the existence of 92
      peptides that map to previously un-annotated regions of the viral genome. Twenty
      one of the newly termed "intergenic peptides" were predicted to have a viable ORF
      around them. Twelve of these produced an mRNA transcript as demonstrated by
      strand-specific RT-PCR. We further characterized the 5' and 3' termini of one
      mRNA transcript, ORF-A, and detected a 55 kDa protein produced during active
      infection using a custom-synthesized antibody. We conclude that the coding
      potential of BoHV-1 is underestimated.

PMID- 30223482
TI  - Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory
      Nutraceuticals against Doxorubicin-Induced Cardiotoxicity.
AB  - Doxorubicin is a highly active antineoplastic agent, but its clinical use is
      limited because of its cardiotoxicity. Although nutraceuticals endowed with anti
      inflammatory properties exert cardioprotective activity, their bioavailability
      and stability are inconsistent. In an attempt to address this issue, we evaluated
      whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin and fresh
      and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells)
      from doxorubicin-induced toxicity. Nanoemulsions were produced with a high
      pressure homogenizer. H9C2 cells were incubated with nanoemulsions loaded with
      different nutraceuticals alone or in combination with doxorubicin. Cell viability
      was evaluated with a modified MTT method. The levels of the lipid peroxidation
      products malondialdehyde (MDA) and 4-hydroxy-2-butanone (4-HNA), and of the
      cardiotoxic-related interleukins IL-6, IL-8, IL-1beta and IL-10, tumor necrosis
      factor-alpha (TNF-alpha), and nitric oxide were analyzed in cardiomyoblasts. The
      hydrodynamic size of nanoemulsions was around 100 nm. Cell viability enhancement
      was 35-40% higher in cardiomyoblasts treated with nanoemulsion + doxorubicin than
      in cardiomyoblasts treated with doxorubicin alone. Nanoemulsions also protected
      against oxidative stress as witnessed by a reduction of MDA and 4-HNA. Notably,
      nanoemulsions inhibited the release of IL-6, IL-8, IL-1beta, TNF-alpha and nitric
      oxide by around 35-40% and increased IL-10 production by 25-27% versus cells not
      treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich
      nanoemulsions had the best cardioprotective profile. In conclusion, nanoemulsions
      loaded with the nutraceuticals described herein protect against cardiotoxicity,
      by reducing inflammation and lipid oxidative stress. These results set the stage
      for studies in preclinical models.

PMID- 30223483
TI  - Cytotoxic Tetrahydroxanthone Dimers from the Mangrove-Associated Fungus
      Aspergillus versicolor HDN1009.
AB  - Three new tetrahydroxanthone dimers, 5-epi-asperdichrome (1), versixanthones N
      (2), and O (3), were isolated from the mangrove-derived fungus Aspergillus
      versicolor HDN1009. Their structures, including the absolute configurations, were
      elucidated by NMR, HRMS, and circular dichroism (CD) experiments. Among them,
      compound 1 was the second example of tetrahydroxanthone dimers, which dimerized
      by a rare diaryl ether linkage and showed promising antibacterial activities
      against Vibrio parahemolyticus, Bacillus subtilis, Mycobacterium phlei, and
      Pseudomonas aeruginosa, with MIC values ranging from 100 MUM to 200 MUM; whilst
      compounds 2 and 3 exhibited extensive cytotoxicities against five cancer cell
      lines (HL-60, K562, H1975, MGC803, and HO-8910), with IC50 values ranging from
      1.7 MUM to 16.1 MUM.

PMID- 30223484
TI  - Proliferative and Invasive Colorectal Tumors in Pet Dogs Provide Unique Insights
      into Human Colorectal Cancer.
AB  - Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer
      model. To better use this resource, we performed an initial global comparison
      between proliferative and invasive colorectal tumors from 20 canine cases, and
      evaluated their molecular homology to human colorectal cancer (CRC). First,
      proliferative canine tumors harbor overactivated WNT/beta-catenin pathways and
      recurrent CTNNB1 (beta-catenin) mutations S45F/P, D32Y and G34E. Invasive canine
      tumors harbor prominent fibroblast proliferation and overactivated stroma. Both
      groups have recurrent TP53 mutations. We observed three invasion patterns in
      canine tumors: collective, crypt-like and epithelial-mesenchymal transition
      (EMT). We detected enriched Helicobacter bilis and Alistipes finegoldii in
      proliferative and crypt-like tumors, but depleted mucosa-microbes in the EMT
      tumor. Second, guided by our canine findings, we classified 79% of 478 human
      colon cancers from The Cancer Genome Atlas into four subtypes: primarily
      proliferative, or with collective, crypt-like or EMT invasion features. Their
      molecular characteristics match those of canine tumors. We showed that consensus
      molecular subtype 4 (mesenchymal) of human CRC should be further divided into EMT
      and crypt-like subtypes, which differ in TGF-beta activation and mucosa-microbe
      content. Our canine tumors share the same pathogenic pathway as human CRCs. Dog
      human integration identifies three CRC invasion patterns and improves CRC
      subtyping.

PMID- 30223485
TI  - Mackerel-Derived Fermented Fish Oil Promotes Hair Growth by Anagen-Stimulating
      Pathways.
AB  - Hair growth is regulated by the interaction between dermal papilla cells (DPC)
      and other cells inside the hair follicle. Here, we show the effect and action
      mechanism of mackerel-derived fermented fish oil (FFO) extract and its component
      docosahexaenoic acid (DHA) in the control of hair growth. The hair growth effect
      of FFO extract was evaluated by the culture method of vibrissa follicles and in
      vivo dotmatrix planimetry method. FFO extract increased the length of hair-fibers
      and enabled stimulated initiation into the anagen phase of the hair cycle. As
      expected, FFO extract significantly increased DPC proliferation. FFO extract
      induced the progression of the cell cycle and the activation of extracellular
      signal-regulated kinase (ERK), p38 and Akt. FFO extract induced nuclear
      translocation of beta-catenin, a stimulator of anagen phase, through an increase
      of phospho-glycogen synthase kinase3beta (GSK3beta) level. Since various
      prostaglandins are known to promote hair growth in humans and mice, we examined
      the effect of DHA, a main omega-3 fatty acid of FFO, on DPC proliferation. DHA
      not only increased DPC proliferation but also upregulated levels of cell cycle
      associated proteins such as cyclin D1 and cdc2 p34. These results show that FFO
      extract and DHA promote hair growth through the anagen-activating pathways in
      DPC.

PMID- 30223487
TI  - Extended Targeted and Non-Targeted Strategies for the Analysis of Marine Toxins
      in Mussels and Oysters by (LC-HRMS).
AB  - When considering the geographical expansion of marine toxins, the emergence of
      new toxins and the associated risk for human health, there is urgent need for
      versatile and efficient analytical methods that are able to detect a range, as
      wide as possible, of known or emerging toxins. Current detection methods for
      marine toxins rely on a priori defined target lists of toxins and are generally
      inappropriate for the detection and identification of emerging compounds. The
      authors describe the implementation of a recent approach for the non-targeted
      analysis of marine toxins in shellfish with a focus on a comprehensive workflow
      for the acquisition and treatment of the data generated after liquid
      chromatography coupled with high resolution mass spectrometry (LC-HRMS) analysis.
      First, the study was carried out in targeted mode to assess the performance of
      the method for known toxins with an extended range of polarities, including
      lipophilic toxins (okadaic acid, dinophysistoxins, azaspiracids, pectenotoxins,
      yessotoxins, cyclic imines, brevetoxins) and domoic acid. The targeted method,
      assessed for 14 toxins, shows good performance both in mussel and oyster
      extracts. The non-target potential of the method was then challenged via suspects
      and without a priori screening by blind analyzing mussel and oyster samples
      spiked with marine toxins. The data processing was optimized and successfully
      identified the toxins that were spiked in the blind samples.

PMID- 30223488
TI  - Bergamot Polyphenol Fraction Exerts Effects on Bone Biology by Activating ERK 1/2
      and Wnt/beta-Catenin Pathway and Regulating Bone Biomarkers in Bone Cell
      Cultures.
AB  - Epidemiological studies show that fruit consumption may modulate bone mineral
      density. However, data regarding the effect of the Citrus bergamia Risso
      (Bergamot orange), a citrus fruit containing a high concentration of flavonoids,
      on bone health are still lacking. In this study, we investigated the effects of
      Bergamot polyphenols on the Wnt/beta-catenin pathway in two distinct bone cell
      types (Saos-2 and MG63). Findings showed that exposure to 0.01 and 0.1 mg/mL
      doses upregulate beta-catenin expression (p = 0.001), osteoblast differentiation
      markers (e.g., RUNX2 and COL1A), and downregulate RANKL (p = 0.028), as compared
      to the control. Our results highlight, for the first time, that Bergamot
      polyphenols act on bone cells through the beta-catenin pathway. In vivo studies
      are necessary to fully understand Bergamot's role against bone resorption.

PMID- 30223486
TI  - UV-Protective Compounds in Marine Organisms from the Southern Ocean.
AB  - Solar radiation represents a key abiotic factor in the evolution of life in the
      oceans. In general, marine, biota-particularly in euphotic and dysphotic zones
      depends directly or indirectly on light, but ultraviolet radiation (UV-R) can
      damage vital molecular machineries. UV-R induces the formation of reactive oxygen
      species (ROS) and impairs intracellular structures and enzymatic reactions. It
      can also affect organismal physiologies and eventually alter trophic chains at
      the ecosystem level. In Antarctica, physical drivers, such as sunlight, sea-ice,
      seasonality and low temperature are particularly influencing as compared to other
      regions. The springtime ozone depletion over the Southern Ocean makes organisms
      be more vulnerable to UV-R. Nonetheless, Antarctic species seem to possess
      analogous UV photoprotection and repair mechanisms as those found in organisms
      from other latitudes. The lack of data on species-specific responses towards
      increased UV-B still limits the understanding about the ecological impact and the
      tolerance levels related to ozone depletion in this region. The photobiology of
      Antarctic biota is largely unknown, in spite of representing a highly promising
      reservoir in the discovery of novel cosmeceutical products. This review compiles
      the most relevant information on photoprotection and UV-repair processes
      described in organisms from the Southern Ocean, in the context of this unique
      marine polar environment.

PMID- 30223490
TI  - Advanced Radar Absorbing Ceramic-Based Materials for Multifunctional Applications
      in Space Environment.
AB  - In this review, some results of the experimental activity carried out by the
      authors on advanced composite materials for space applications are reported.
      Composites are widely employed in the aerospace industry thanks to their
      lightweight and advanced thermo-mechanical and electrical properties. A critical
      issue to tackle using engineered materials for space activities is providing two
      or more specific functionalities by means of single items/components. In this
      scenario, carbon-based composites are believed to be ideal candidates for the
      forthcoming development of aerospace research and space missions, since a
      widespread variety of multi-functional structures are allowed by employing these
      materials. The research results described here suggest that hybrid
      ceramic/polymeric structures could be employed as spacecraft-specific subsystems
      in order to ensure extreme temperature withstanding and electromagnetic shielding
      behavior simultaneously. The morphological and thermo-mechanical analysis of
      carbon/carbon (C/C) three-dimensional (3D) shell prototypes is reported; then,
      the microwave characterization of multilayered carbon-filled micro-/nano
      composite panels is described. Finally, the possibility of combining the C/C bulk
      with a carbon-reinforced skin in a synergic arrangement is discussed, with the
      aid of numerical and experimental analyses.

PMID- 30223489
TI  - Large-Scale Screening of HCMV-Seropositive Blood Donors Indicates that HCMV
      Effectively Escapes from Antibodies by Cell-Associated Spread.
AB  - Immunoglobulins are only moderately effective for the treatment of human
      cytomegalovirus (HCMV) infections, possibly due to ineffectiveness against cell
      associated virus spread. To overcome this limitation, we aimed to identify
      individuals with exceptional antibodies in their plasma that can efficiently
      block the cell-associated spread of HCMV. A Gaussia luciferase-secreting mutant
      of the cell-associated HCMV strain Merlin was generated, and luciferase activity
      evaluated as a readout for the extent of cell-associated focal spread. This
      reporter virus-based assay was then applied to screen plasma samples from 8400
      HCMV-seropositive individuals for their inhibitory effect, including direct
      acting antiviral drugs as positive controls. None of the plasmas reduced virus
      spread to the level of these controls. Even the top-scoring samples that
      partially reduced luciferase activity in the screening assay failed to inhibit
      focal growth when reevaluated with a more accurate, immunofluorescence-based
      assay. Selected sera with high neutralizing capacity against free viruses were
      analyzed separately, and none of them prevented the focal spread of three recent
      clinical HCMV isolates nor reduced the number of particles transmitted, as
      demonstrated with a fluorescent Merlin mutant. We concluded that donors with cell
      to-cell-spread-inhibiting plasma are nonexistent or extremely rare, emphasizing
      cell-associated spread as a highly efficient immune escape mechanism of HCMV.

PMID- 30223491
TI  - Preparation and Characteristics of Biocomposites Based on Steam Exploded Sisal
      Fiber Modified with Amphipathic Epoxidized Soybean Oil Resin.
AB  - Sisal fiber was pretreated by continuous screw extrusion steam explosion to
      prepare steam exploded sisal fiber (SESF) preforms. An amphipathic bio-based
      thermosetting resin with poor mechanical properties was cured by epoxidized
      soybean oil (ESO) and citric acid (CA). The obtained resin was used to modify
      SESF preforms and prepare eco-friendly biocomposites. The molar ratios (R) of
      carboxylic groups to epoxy groups and resin contents in biocomposites were
      adjusted. The biocomposites were characterized by thermogravimetric analysis
      (TGA), differential scanning calorimetry (DSC), Fourier-transfer infrared
      spectroscopy (FT-IR), tensile testing, scanning electron microscopy (SEM), water
      absorption and water contact angle measurements. The maximum thermal
      decomposition temperature of the biocomposites was 373.1  degrees C. The curing
      efficiency of the resin in the biocomposites improved with the increase of resin
      content, and reached a maximum at R = 1.2. The tensile strength of the
      biocomposites reached a maximum of 30.4 MPa at R = 1.2 and 40% resin content. SEM
      images showed excellent interfacial bonding and fracture mechanisms within the
      biocomposites. The biocomposites exhibited satisfactory water resistance. ESO
      resin cured with polybasic carboxylic acid is therefore a good bio-based modifier
      for lignocellulose, that prepare biocomposites with good mechanical properties,
      hydrophobicity, and thermostability, and which has a potential application in
      packaging.

PMID- 30223492
TI  - Insight into the Self-Assembling Properties of Peptergents: A Molecular Dynamics
      Simulation Study.
AB  - By manipulating the various physicochemical properties of amino acids, the design
      of peptides with specific self-assembling properties has been emerging for more
      than a decade. In this context, short peptides possessing detergent properties
      (so-called "peptergents") have been developed to self-assemble into well-ordered
      nanostructures that can stabilize membrane proteins for crystallization. In this
      study, the peptide with "peptergency" properties, called ADA8 and extensively
      described by Tao et al., is studied by molecular dynamic simulations for its self
      assembling properties in different conditions. In water, it spontaneously forms
      beta sheets with a beta barrel-like structure. We next simulated the interaction
      of this peptide with a membrane protein, the bacteriorhodopsin, in the presence
      or absence of a micelle of dodecylphosphocholine. According to the literature,
      the peptergent ADA8 is thought to generate a belt of beta structures around the
      hydrophobic helical domain that could help stabilize purified membrane proteins.
      Molecular dynamic simulations are here used to image this mechanism and provide
      further molecular details for the replacement of detergent molecules around the
      protein. In addition, we generalized this behavior by designing an amphipathic
      peptide with beta propensity, which was called ABZ12. Both peptides are able to
      surround the membrane protein and displace surfactant molecules. To our best
      knowledge, this is the first molecular mechanism proposed for "peptergency".

PMID- 30223493
TI  - Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of
      the Hepatitis C Virus.
AB  - HCV genotype 2a strain JFH-1 replicates and produces viral particles efficiently
      in human hepatocellular carcinoma (huh) 7.5 cells, which provide a stable in
      vitro cell infection system for the hepatitis C virus (HCVcc system). Natural
      killer (NK) cells are large lymphoid cells that recognize and kill virus-infected
      cells. In this study, we investigated the interaction between NK cells and the
      HCVcc system. IL-10 is a typical immune regulatory cytokine that is produced
      mostly by NK cells and macrophages. IL-21 is one of the main cytokines that
      stimulate the activation of NK cells. First, we used anti-IL-10 to neutralize IL
      10 in a coculture of NK cells and HCVcc. Anti-IL-10 treatment increased the
      maturation of NK cells by enhancing the frequency of the CD56+dim population in
      NK-92 cells. However, with anti-IL-10 treatment of NK cells in coculture with
      J6/JFH-1-huh 7.5 cells, there was a significant decrease in the expression of
      STAT1 and STAT5 proteins in NK-92 cells and an increase in the HCV Core and NS3
      proteins. In addition, rIL-21 treatment increased the frequency of the CD56+dim
      population in NK-92 cells, Also, there was a dramatic increase in the expression
      of STAT1 and STAT5 proteins in rIL-21 pre-stimulated NK cells and a decrease in
      the expression of HCV Core protein in coculture with J6/JFH-1-huh 7.5 cells. In
      summary, we found that the functional activation of NK cells can be modulated by
      anti-IL-10 or rIL-21, which controls the expression of HCV proteins as well as
      HCV RNA replication.

PMID- 30223495
TI  - Automatic Calibration of Odometry and Robot Extrinsic Parameters Using Multi
      Composite-Targets for a Differential-Drive Robot with a Camera.
AB  - This paper simultaneously calibrates odometry parameters and the relative pose
      between a monocular camera and a robot automatically. Most camera pose estimation
      methods use natural features or artificial landmark tools. However, there are
      mismatches and scale ambiguity for natural features; the large-scale precision
      landmark tool is also challenging to make. To solve these problems, we propose an
      automatic process to combine multiple composite targets, select keyframes, and
      estimate keyframe poses. The composite target consists of an aruco marker and a
      checkerboard pattern. First, an analytical method is applied to obtain initial
      values of all calibration parameters; prior knowledge of the calibration
      parameters is not required. Then, two optimization steps are used to refine the
      calibration parameters. Planar motion constraints of the camera are introduced in
      these optimizations. The proposed solution is automatic; manual selection of
      keyframes, initial values, and robot construction within a specific trajectory
      are not required. The competing accuracy and stability of the proposed method
      under different target placements and robot paths are tested experimentally.
      Positive effects on calibration accuracy and stability are obtained when (1)
      composite targets are adopted; (2) two optimization steps are used; (3) plane
      motion constraints are introduced; and (4) target numbers are increased.

PMID- 30223496
TI  - Imaging Time Series for the Classification of EMI Discharge Sources.
AB  - In this work, we aim to classify a wider range of Electromagnetic Interference
      (EMI) discharge sources collected from new power plant sites across multiple
      assets. This engenders a more complex and challenging classification task. The
      study involves an investigation and development of new and improved feature
      extraction and data dimension reduction algorithms based on image processing
      techniques. The approach is to exploit the Gramian Angular Field technique to map
      the measured EMI time signals to an image, from which the significant information
      is extracted while removing redundancy. The image of each discharge type contains
      a unique fingerprint. Two feature reduction methods called the Local Binary
      Pattern (LBP) and the Local Phase Quantisation (LPQ) are then used within the
      mapped images. This provides feature vectors that can be implemented into a
      Random Forest (RF) classifier. The performance of a previous and the two new
      proposed methods, on the new database set, is compared in terms of classification
      accuracy, precision, recall, and F-measure. Results show that the new methods
      have a higher performance than the previous one, where LBP features achieve the
      best outcome.

PMID- 30223497
TI  - Can the Fact That Myelin Proteins Are Old and Break down Explain the Origin of
      Multiple Sclerosis in Some People?
AB  - Recent discoveries may change the way that multiple sclerosis (MS) is viewed,
      particularly with regard to the reasons for the untoward immune response. The
      fact that myelin proteins are long-lived, and that by the time we are adults,
      they are extensively degraded, alters our perspective on the reasons for the
      onset of autoimmunity and the origin of MS. For example, myelin basic protein
      (MBP) from every human brain past the age of 20 years, is so greatly modified,
      that it is effectively a different protein from the one that was laid down in
      childhood. Since only a subset of people with such degraded MBP develop MS, a
      focus on understanding the mechanism of immune responses to central nervous
      system (CNS) antigens and cerebral immune tolerance appear to be worthwhile
      avenues to explore. In accord with this, it will be productive to examine why all
      people, whose brains contain large quantities of a "foreign antigen", do not
      develop MS. Importantly for the potential causation of MS, MBP from MS patients
      breaks down differently from the MBP in aged controls. If the novel structures
      formed in these MS-specific regions are particularly antigenic, it could help
      explain the origin of MS. If verified, these findings could provide an avenue for
      the rational synthesis of drugs to prevent and treat MS.

PMID- 30223498
TI  - Detection of Volatile Constituents from Food Lures by Tephritid Fruit Flies.
AB  - Tephritid fruit flies require protein for sexual and gonotrophic development.
      Food-based lures are therefore widely used in strategies to detect and control
      fruit flies in the Tephritidae family. However, these baits are attractive to a
      broad range of insect species. We therefore sought to identify volatiles detected
      by the fly antennae, with the goal to compose lures that more specifically target
      tephritids. Using gas chromatography-coupled electroantennographic detection (GC
      EAD) we screened for antennal responses of four important tephritid species to
      volatile compounds from five commercially available protein-based baits. Antennal
      active compounds were reconstituted in synthetic blends for each species and used
      in behavioral assays. These species-based blends were attractive in olfactometer
      experiments, as was a blend composed of all antennally active compounds from all
      the four species we observed (tested only in Bactrocera dorsalis, Hendel). Pilot
      field tests indicate that the blends need to be further evaluated and optimized
      under field conditions.

PMID- 30223494
TI  - Telocinobufagin and Marinobufagin Produce Different Effects in LLC-PK1 Cells: A
      Case of Functional Selectivity of Bufadienolides.
AB  - Bufadienolides are cardiotonic steroids (CTS) identified in mammals. Besides
      Na+/K+-ATPase inhibition, they activate signal transduction via protein-protein
      interactions. Diversity of endogenous bufadienolides and mechanisms of action may
      indicate the presence of functional selectivity and unique cellular outcomes. We
      evaluated whether the bufadienolides telocinobufagin and marinobufagin induce
      changes in proliferation or viability of pig kidney (LLC-PK1) cells and the
      mechanisms involved in these changes. In some experiments, ouabain was used as a
      positive control. CTS exhibited an inhibitory IC50 of 0.20 (telocinobufagin),
      0.14 (ouabain), and 3.40 MUM (marinobufagin) for pig kidney Na+/K+-ATPase
      activity and concentrations that barely inhibited it were tested in LLC-PK1
      cells. CTS induced rapid ERK1/2 phosphorylation, but corresponding proliferative
      response was observed for marinobufagin and ouabain instead of telocinobufagin.
      Telocinobufagin increased Bax:Bcl-2 expression ratio, sub-G0 cell cycle phase and
      pyknotic nuclei, indicating apoptosis. Src and MEK1/2 inhibitors blunted
      marinobufagin but not telocinobufagin effect, which was also not mediated by p38,
      JNK1/2, and PI3K. However, BIO, a GSK-3beta inhibitor, reduced proliferation and,
      as telocinobufagin, phosphorylated GSK-3beta at inhibitory Ser9. Combination of
      both drugs resulted in synergistic antiproliferative effect. Wnt reporter
      activity assay showed that telocinobufagin impaired Wnt/beta-catenin pathway by
      acting upstream to beta-catenin stabilization. Our findings support that
      mammalian endogenous bufadienolides may exhibit functional selectivity.

PMID- 30223499
TI  - Origin of the Low Magnetic Moment in Fe2AlTi: An Ab Initio Study.
AB  - The intermetallic compound Fe 2 AlTi (alternatively Fe 2 TiAl) is an important
      phase in the ternary Fe-Al-Ti phase diagram. Previous theoretical studies showed
      a large discrepancy of approximately an order of magnitude between the ab initio
      computed magnetic moments and the experimentally measured ones. To unravel the
      source of this discrepancy, we analyze how various mechanisms present in
      realistic materials such as residual strain effects or deviations from
      stoichiometry affect magnetism. Since in spin-unconstrained calculations the
      system always evolves to the spin configuration which represents a local or
      global minimum in the total energy surface, finite temperature spin effects are
      not well described. We therefore turn the investigation around and use
      constrained spin calculations, fixing the global magnetic moment. This approach
      provides direct insight into local and global energy minima (reflecting
      metastable and stable spin phases) as well as the curvature of the energy
      surface, which correlates with the magnetic entropy and thus the magnetic
      configuration space accessible at finite temperatures. Based on this approach, we
      show that deviations from stoichiometry have a huge impact on the local magnetic
      moment and can explain the experimentally observed low magnetic moments.

PMID- 30223500
TI  - Beliefs about Binge Eating: Psychometric Properties of the Eating Beliefs
      Questionnaire (EBQ-18) in Eating Disorder, Obese, and Community Samples.
AB  - Binge eating is a core diagnostic feature of bulimia nervosa, binge eating
      disorder, anorexia nervosa binge/purge type, and is a common feature of "other
      specified" and "unspecified" feeding and eating disorders. It has been suggested
      that specific metacognitive beliefs about food, eating, and binge eating may play
      a key role in the maintenance of binge eating behaviour. The Eating Beliefs
      Questionnaire (EBQ-18) provides a brief self-report assessment tool measuring
      three types of metacognitive beliefs: negative, positive, and permissive beliefs
      about food and eating. This study aimed to build on past research by validating
      the factor structure and psychometric properties of the EBQ-18 using both a
      clinical and non-clinical sample. A sample of 688 participants (n = 498 non
      clinical participants, n = 161 participants seeking treatment for an eating
      disorder, and n = 29 participants seeking treatment for obesity) completed a
      battery of questionnaires, including the EBQ-18 and other measures of eating
      disorder symptoms and relevant constructs. A subset of 100 non-clinical
      participants completed the test battery again after an interval of two-weeks, and
      38 clinical participants completed the EBQ-18 before and after receiving
      psychological treatment for their eating disorder. A confirmatory factor analysis
      (CFA) was conducted and psychometric properties of this measure were assessed.
      The results of this study provide support for the three-factor model of the EBQ
      18. In addition, the EBQ-18 was found to be a valid and reliable measure, with
      excellent internal consistency, good test-retest reliability in the non-clinical
      sample, and also demonstrated evidence of sensitivity to treatment in clinical
      samples with binge eating pathology. Receiver operating characteristic (ROC)
      curve analyses were used to identify optimal cut-off scores for the EBQ-18. This
      study provides valuable information about the utility of the EBQ-18 as a measure
      for use in both clinical and research settings.

PMID- 30223501
TI  - Dense RGB-D Semantic Mapping with Pixel-Voxel Neural Network.
AB  - In this paper, a novel Pixel-Voxel network is proposed for dense 3D semantic
      mapping, which can perform dense 3D mapping while simultaneously recognizing and
      labelling the semantic category each point in the 3D map. In our approach, we
      fully leverage the advantages of different modalities. That is, the PixelNet can
      learn the high-level contextual information from 2D RGB images, and the VoxelNet
      can learn 3D geometrical shapes from the 3D point cloud. Unlike the existing
      architecture that fuses score maps from different modalities with equal weights,
      we propose a softmax weighted fusion stack that adaptively learns the varying
      contributions of PixelNet and VoxelNet and fuses the score maps according to
      their respective confidence levels. Our approach achieved competitive results on
      both the SUN RGB-D and NYU V2 benchmarks, while the runtime of the proposed
      system is boosted to around 13 Hz, enabling near-real-time performance using an
      i7 eight-cores PC with a single Titan X GPU.

PMID- 30223502
TI  - A Feasibility Study on Timber Moisture Monitoring Using Piezoceramic Transducer
      Enabled Active Sensing.
AB  - In recent years, the piezoceramic transducer-enabled active sensing technique has
      been extensively applied to structural damage detection and health monitoring, in
      civil engineering. Being abundant and renewable, timber has been widely used as a
      building material in many countries. However, one of the more challenging
      applications of timber, in construction, is the potential damage caused by
      moisture. Increased moisture may cause easier warping of timber components and
      encourage corrosion of integrated metal members, on top of potentially causing
      rot and decay. However, despite numerous efforts to inspect and monitor the
      moisture content of timber, there lacks a method that can provide truly real
      time, quantitative, and non-invasive measurement of timber moisture. Thus, the
      research presented in this paper investigated the feasibility of moisture-content
      monitoring using an active sensing approach, as enabled by a pair of the Lead
      Zirconate Titanate (PZT) transducers bonded on the surface of a timber specimen.
      Using a pair of transducers in an active sensing scheme, one patch generated a
      designed stress wave, while another patch received the signal. While the active
      sensing was active, the moisture content of the timber specimen was gradually
      increased from 0% to 60% with 10% increments. The material properties of the
      timber correspondingly changed under varying timber moisture content, resulting
      in a measurable differential in stress wave attenuation rates among the different
      specimens used. The experimental results indicated that the received signal
      energy and the moisture content of the timber specimens show a parabolic
      relationship. Finally, the feasibility and reliability of the presented method,
      for monitoring timber moisture content, are discussed.

PMID- 30223503
TI  - The Cytoscan HD Array in the Diagnosis of Neurodevelopmental Disorders.
AB  - Submicroscopic chromosomal copy number variations (CNVs), such as deletions and
      duplications, account for about 15-20% of patients affected with developmental
      delay, intellectual disability, multiple congenital anomalies, and autism
      spectrum disorder. Most of CNVs are de novo or inherited rearrangements with
      clinical relevance, but there are also rare inherited imbalances with unknown
      significance that make difficult the clinical management and genetic counselling.
      Chromosomal microarrays analysis (CMA) are recognized as the first-line test for
      CNV detection and are now routinely used in the clinical diagnostic laboratory.
      The recent use of CMA platforms that combine classic copy number analysis with
      single-nucleotide polymorphism (SNP) genotyping has increased the diagnostic
      yields. Here we discuss the application of the Cytoscan high-density (HD) SNP
      array for the detection of CNVs. We provide an overview of molecular analyses
      involved in identifying pathogenic CNVs and highlight important guidelines to
      establish pathogenicity of CNV.

PMID- 30223504
TI  - Implementation Efficiency of Corporate Social Responsibility in the Construction
      Industry: A China Study.
AB  - Corporate social responsibility (CSR), as companies' commitment to the
      sustainable development of the whole society, is an important approach for
      construction companies to respond to the emerging social and environmental
      issues. As the improvement of CSR efficiency leads to the reduction of CSR cost,
      CSR efficiency is becoming increasingly prominent for construction companies. In
      this research, the three-stage data envelopment analysis (DEA) model is adopted
      to analyze the CSR efficiency of Chinese construction companies in the period of
      2012-2016. The findings of this research are as follows: (1) the efficiency of
      the Chinese construction companies in fulfilling CSR has not yet reached an
      optimal level; (2) the effect of institutional factors on CSR efficiency is
      complex and non-linear; and (3) the improvement of the CSR efficiency in the
      Chinese construction industry relies on both optimizing the institutional
      environment and enhancing the management capacity of CSR efficiency. These
      findings can not only provide empirical evidence for the government to formulate
      targeted policy-making regarding marketization to promote construction companies'
      efficient commitment of CSR, but also provide construction company managers a
      valuable reference to benchmarking the CSR efficiency to help them find self
      improvement ways to improve CSR efficiency performance.

PMID- 30223505
TI  - It Takes a Village: Multidisciplinary Approach to Screening and Prevention of
      Pediatric Sleep Issues.
AB  - Sleep is essential to human development. Poor sleep can have significant effects
      on cognition, learning and memory, physical and behavioral health, and social
      emotional well-being. This paper highlights the prevalence of common pediatric
      sleep problems and posits that a multidisciplinary approach to the assessment and
      intervention of sleep problems is ideal. Primary care providers are often the
      first professionals to discuss sleep issues with youth and families. However,
      dentists, otolaryngologists, childcare providers, school personnel, and
      behavioral health providers have a vital role in screening and prevention,
      providing intervention, and monitoring the progress of daily functioning. The
      strengths of this approach include better provider-to-provider and provider-to
      family communication, streamlined assessment and intervention, earlier
      identification of sleep issues with more efficient referral, and longer-term
      monitoring of progress and impact on daily functioning. Barriers to this approach
      include difficulty initiating and maintaining collaboration among providers,
      limited provider time to obtain the necessary patient permission to collaborate
      among all multidisciplinary providers, lack of financial support for consultation
      and collaboration outside of seeing patients face-to-face, geographic location,
      and limited resources within communities. Research investigating the utility of
      this model and the overall impact on pediatric patient sleep issues is warranted
      and strongly encouraged.

PMID- 30223507
TI  - Development of a Novel Methodology to Assess the Corrosion Threshold in Concrete
      Based on Simultaneous Monitoring of pH and Free Chloride Concentration.
AB  - Both the free chloride concentration and the pH of the concrete pore solution are
      highly relevant parameters that control corrosion of the reinforcing steel. In
      this paper, we present a method to continuously monitor these two parameters in
      situ. The approach is based on a recently developed electrode system that
      consists of several different potentiometric sensors as well as a data
      interpretation procedure. Instrumented mortar specimens containing different
      amounts of admixed chlorides were exposed to accelerated carbonation, and changes
      in free chloride concentration and pH were monitored simultaneously over time.
      The results revealed the stepwise decrease in pH as well as corresponding
      increases in free chlorides, resulting from the release of bound chlorides. For a
      pH drop of about 1 unit (from pH 13.5 down to pH 12.5), the free chloride
      concentration increased up to 1.5-fold. We continuously quantified the ratio Cl
      /OH- that increased steeply with time, and was found to exceed a critical
      corrosion threshold long before carbonation can be detected with traditional
      indicator spray testing, even at admixed chloride contents in the order of
      allowable limits. These results can strongly influence the decision-making in
      engineering practice and it is expected to significantly improve condition
      assessments of reinforced concrete structures.

PMID- 30223506
TI  - Apolipoprotein E Epsilon 4 Genotype, Mild Traumatic Brain Injury, and the
      Development of Chronic Traumatic Encephalopathy.
AB  - The annual incidence of mild traumatic brain injury (MTBI) is 3.8 million in the
      USA with 10-15% experiencing persistent morbidity beyond one year. Chronic
      traumatic encephalopathy (CTE), a neurodegenerative disease characterized by
      accumulation of hyperphosphorylated tau, can occur with repetitive MTBI. Risk
      factors for CTE are challenging to identify because injury mechanisms of MTBI are
      heterogeneous, clinical manifestations and management vary, and CTE is a
      postmortem diagnosis, making prospective studies difficult. There is growing
      interest in the genetic influence on head trauma and development of CTE.
      Apolipoprotein epsilon 4 (APOE-epsilon4) associates with many neurologic
      diseases, and consensus on the epsilon4 allele as a risk factor is lacking. This
      review investigates the influence of APOE-epsilon4 on MTBI and CTE. A
      comprehensive PubMed literature search (1966 to 12 June 2018) identified 24
      unique reports on the topic (19 MTBI studies: 8 athletic, 5 military, 6
      population-based; 5 CTE studies: 4 athletic and military, 1 leucotomy group).
      APOE-epsilon4 genotype is found to associate with outcomes in 4/8 athletic
      reports, 3/5 military reports, and 5/6 population-based reports following MTBI.
      Evidence on the association between APOE-epsilon4 and CTE from case series is
      equivocal. Refining modalities to aid CTE diagnosis in larger samples is needed
      in MTBI.

PMID- 30223508
TI  - Correction: Yan, L., et al. A Micro Bubble Structure Based Fabry-Perot Optical
      Fiber Strain Sensor with High Sensitivity and Low-Cost Characteristics Sensors,
      2017, 17, 555.
AB  - An correction is presented to correct Figure 5a in [Sensors, 2017, 17, 555].

PMID- 30223509
TI  - Radar Emitter Recognition Based on the Energy Cumulant of Short Time Fourier
      Transform and Reinforced Deep Belief Network.
AB  - To cope with the complex electromagnetic environment and varied signal styles, a
      novel method based on the energy cumulant of short time Fourier transform and
      reinforced deep belief network is proposed to gain a higher correct recognition
      rate for radar emitter intra-pulse signals at a low signal-to-noise ratio. The
      energy cumulant of short time Fourier transform is attained by calculating the
      accumulations of each frequency sample value with the different time samples.
      Before this procedure, the time frequency distribution via short time Fourier
      transform is processed by base noise reduction. The reinforced deep belief
      network is proposed to employ the input feature vectors for training to achieve
      the radar emitter recognition and classification. Simulation results manifest
      that the proposed method is feasible and robust in radar emitter recognition even
      at a low SNR.

PMID- 30223510
TI  - Investigation of Energy Transfer in Star-Shaped White Polymer Light-Emitting
      Devices via the Time-Resolved Photoluminescence.
AB  - A series of white polymer light-emitting devices (WPLEDs) were fabricated by
      utilizing star-shaped white-emission copolymers containing tri[1
      phenylisoquinolinato-C2,N]iridium (Ir(piq)3), fluorenone (FO) and poly(9,9
      dioctylfluorene) (PFO) as red-, green- and blue-emitting (RGB) components,
      respectively. In these WPLEDs, a maximum current efficiency of 6.4 cd.A-1 at 20
      mA.cm-2 and Commission Internationale d'Eclairage (CIE) coordinates of (0.33,
      0.32) were achieved, and the current efficiency was still kept to 4.2 cd.A-1 at
      the current density of 200 mA.cm-2. To investigate energy transfer processes
      among the three different chromophores of the star-shaped copolymers in these
      WPLEDs, the time-resolved photoluminescence (PL) spectra were recorded. By
      comparing the fluorescence decay lifetimes of PFO chromophores in the four star
      like white-emitting copolymers, the efficient energy transfer from PFO units to
      Ir(piq)3 and FO chromophores was confirmed. From time-resolved PL and the
      analysis of energy transfer process, the results as follows were proved. Owing to
      the star-like molecular structure and steric hindrance effect, intermolecular
      interactions and concentrations quenching in the electroluminescence (EL) process
      could also be sufficiently suppressed. The efficient energy transfer also reduced
      intermolecular interactions' contribution to the enhanced device performances
      compared to the linear single-polymer white-light systems. Moreover, saturated
      stable white emission results from the joint of energy transfer and trap-assisted
      recombination. This improved performance is expected to provide the star-like
      white-emitting copolymers with promising applications for WPLEDs.

PMID- 30223511
TI  - Biomimetic Mineralizing Agents Recover the Micro Tensile Bond Strength of
      Demineralized Dentin.
AB  - Biomimetic remineralization is an approach that mimics natural biomineralization,
      and improves adhesive procedures. The aim of this paper was to investigate the
      influence of Dentin Caries-like Lesions (DCLL)-Producing Model on microtensile
      bond strength (MUTBS) of etch and rinse adhesive systems and investigate the
      effect of remineralizing agents such as Sodium Fluoride (NaF), MI PasteTM (MP)
      and CurodontTM Repair (CR) on caries-affected dentin (n = 6). Nine groups were
      established: (1) Sound dentin; (2) Demineralized dentin/Chemical DCLL: (3)
      Demineralized dentin/Biological DCLL; (4) Chemical/DCLL + NaF; (5) Chemical/DCLL
      + MP; (6) Chemical/DCLL + CR; (7) Biological/DCLL + NaF; (8) Biological/DCLL +
      MP; (9) Biological/DCLL + CR. Then all dentin blocks were subjected to a bonding
      procedure with AdperTM Single Bond 2 adhesive system/Filtek Z350XT 4 mm high
      block, following this they were immersed in deionized water/24 h and then
      sectioned with ? 1 mm2 beams. The MUTBS test was conducted at 1 mm/min/500 N
      loading. Failure sites were evaluated by SEM (scanning electron microscopy
      (150*). MUTBS data were submitted to factorial ANOVA and Tukey's test (p < 0.05).
      The highest values were found when demineralized dentin was treated with MP and
      CR, regardless caries lesion depth (p < 0.05). There was a predominance of
      adhesive/mixed in the present study. It was concluded that the use of the
      artificial dentin caries production models produces differences in the MUTBS.
      Additionally MP and CR remineralizing agents could enhance adhesive procedures
      even at different models of caries lesion.

PMID- 30223512
TI  - Is Sleep Duration Associated with Biological Age (BA)?: Analysis of (2010-2015)
      South Korean NHANES Dataset South Korea.
AB  - (1) Background: South Korea ranked worst in sleep duration compared to other
      countries, but there are no clear healthcare programs to guarantee sufficient
      sleep. Studies are needed to suggest evidence and arouse public awareness of the
      negative effects of abnormal sleep duration. In this study, we investigated the
      relationship between biological age (BA) and sleep duration. (2) Methods: We used
      data from the Korea National Health and Nutrition Examination Surveys (KNHANES V
      VI; 2010-2015, which is an annually cross-sectional study including 29,309
      participants). We performed multiple linear regression to investigate the
      associations between sleep duration and differences in BA and chronological age
      (CA). (3) Results: A total of 14.22% of respondents had short sleep duration
      (less than 6 h per day) and 7.10% of respondents had long sleep duration (more
      than 8 h per day). People with long sleep duration had a positive correlation
      with difference between BA and CA (>8 h per day, beta = 1.308, p-value = 0.0001;
      ref = 6~8 h per day, normal). Short sleep duration had an inverse trend with the
      difference, although the result was not statically significant. Associations were
      greater in vulnerable populations, such as low income, obese, or people with
      chronic diseases. (4) Conclusions: Excess sleep duration that is greater than the
      normal range was associated with increased BA. In particular, such relationships
      that are related to worsening BA were greater in patients with low income,
      obesity, and chronic diseases. Based on our findings, healthcare professionals
      should also consider the negative effects of excess sleep, not only insufficient
      sleep. Alternatives for controlling optimal sleep duration should be reviewed,
      especially with vulnerable populations.

PMID- 30223514
TI  - Transmission Optimization Metrics Setup Issues in the Field of Time Constrained
      Communications.
AB  - This article introduces a new approach in the field of network optimization based
      on Transmission Optimization Metric (TOM), which is aimed at improving traffic
      flow continuity and increasing the chances for traffic flow sustainability in a
      way that helps to minimize inter-packet gaps. The work is mainly focused on harsh
      transmission conditions in narrow-band networks. Finally, the presented approach
      has impact on better resource allocation as fewer attempts are necessary for
      successful completion of a transmission. A significant part of the article deals
      with parameterization of coefficients used by the TOM optimization method.
      Examples of analysis for several topologies of narrow-band wireless networks
      based on CSMA/CA and TDMA protocols are used to demonstrate various issues
      related to proper setting of parameters. The introduced TOM metric has the
      potential to become a standard for optimization, for example, in sensor networks
      that are characterized by the specific nature of data traffic.

PMID- 30223515
TI  - Mineral Trioxide Aggregate Mixed with 5-Aminolevulinic Acid for the Photodynamic
      Antimicrobial Strategy in Hard Tissue Regeneration.
AB  - Aminolevulinic acid (ALA) based photodynamic antimicrobial strategy can provide
      good antimicrobial effects and be used for medical applications. The aim of this
      study was to apply this strategy to Mineral Trioxide Aggregate (MTA), which is
      commonly used as a filling material for root endings and by doing so, to increase
      the bactericidal capability of MTA, as well as to investigate its
      characterization, cytocompatibility, and odontogenic differentiation potential.
      MTA is known to be a derivative of calcium silicate (CS). In this study, MTA
      specimens with or without ALA and light treatment were prepared. Diametral
      tensile strength values (DTS), setting durations, X-ray diffraction (XRD)
      spectra, apatite-mineralization, and antimicrobial abilities of the MTA, were
      also analyzed. Human dental pulp cells (hDPCs) can proliferate into the newly
      formed matrix and differentiate into odontoblasts to reinforce and strengthen the
      root. Levels of hDPCs proliferation and its odontogenic capabilities when
      cultured on MTA with ALA and light treatment, and the percentages of cells
      existing in the various cell cycle stages, were further evaluated in this study.
      The results indicated that MTA added ALA with light treatment had greater
      antibacterial ability and cytocompatibility, compared to MTA alone. A higher
      percentage S phase of the cells cultured on MTA added ALA with light treatment
      was observed. Furthermore, hDPCs cultured on MTA added ALA with light treatment
      had the highest expression levels of the odontoblastic differentiation markers.
      ALA has great antimicrobial efficiency and is a potential material for future
      medical applications. ALA-based photodynamic antibacterial strategy applied in
      the MTA has great antibacterial ability, cytocompatibility, and odontoblastic
      differentiation potential, and can facilitate the development of root canal
      treatment.

PMID- 30223516
TI  - DAQUA-MASS: An ISO 8000-61 Based Data Quality Management Methodology for Sensor
      Data.
AB  - The Internet-of-Things (IoT) introduces several technical and managerial
      challenges when it comes to the use of data generated and exchanged by and
      between various Smart, Connected Products (SCPs) that are part of an IoT system
      (i.e., physical, intelligent devices with sensors and actuators). Added to the
      volume and the heterogeneous exchange and consumption of data, it is paramount to
      assure that data quality levels are maintained in every step of the data
      chain/lifecycle. Otherwise, the system may fail to meet its expected function.
      While Data Quality (DQ) is a mature field, existing solutions are highly
      heterogeneous. Therefore, we propose that companies, developers and vendors
      should align their data quality management mechanisms and artefacts with well
      known best practices and standards, as for example, those provided by ISO 8000
      61. This standard enables a process-approach to data quality management,
      overcoming the difficulties of isolated data quality activities. This paper
      introduces DAQUA-MASS, a methodology based on ISO 8000-61 for data quality
      management in sensor networks. The methodology consists of four steps according
      to the Plan-Do-Check-Act cycle by Deming.

PMID- 30223517
TI  - "Sacbe", a Comprehensive Intervention to Decrease Body Mass Index in Children
      with Adiposity: A Pilot Study.
AB  - Interventions in children with adiposity decrease less than 0.2 the body mass
      index (BMI) z-score less than 0.2 and only in 21-23% of cases. Experts recommend
      focusing on the habits of a healthy lifestyle (HLS) but considering the
      sociocultural context of children and their parents. Our objective was to achieve
      a higher percentage of success in lowering the BMI z-score in children with
      adiposity and their parents through a pilot program "Sacbe" based on HLS,
      sensitive to the sociocultural context previously explored and with the active
      participation of parents. This is a pilot study in children aged 8 to 18 years
      with adiposity according to the BMI z-score. The program consisted of two
      workshops on HLS and nutrition given by the pediatric endocrinologist in group
      sessions with 3-5 families and reinforcements in each visit by registered
      dietitians. We recorded lifestyle habits and anthropometric characteristics of
      children and their parents at the baseline visit and every month for 3-4 months.
      Forty-nine families, 55 children and 64 parents participated, 60% of the children
      were female, the average age was 13.95 +/- 3.3 years, 72.7% and 86.7% lowered the
      z score of the BMI due to intention to treat and protocol analysis (p < 0.001),
      respectively; BMI z-score decreased by 0.22 +/- 0.21, from 2.13 +/- 0.57 to 1.91
      +/- 0.58 (p < 0.001). In total, 83% of the parents involved were mothers, the
      average age was 45.8 +/- 9.4 years, 77% lost weight and body fat (p < 0.001), the
      frequency of unhealthy habits decreased. The results of "Sacbe" exceeded
      expectations by combining the active participation of parents, sessions in
      groups, and the education on various components of an HLS inside sociocultural
      context. The main challenge will be to standardize and reproduce this type of
      complex interventions, as well as to assure long-term success.

PMID- 30223518
TI  - Therapeutic Peptide Amphiphile as a Drug Carrier with ATP-Triggered Release for
      Synergistic Effect, Improved Therapeutic Index, and Penetration of 3D Cancer Cell
      Spheroids.
AB  - Despite the great progress in the field of drug delivery systems for cancer
      treatment over the last decade, many challenges still lie ahead, such as low drug
      loading, deep penetration of tumors, side effects, and the development of drug
      resistance. A class of cationic membrane lytic peptides has shown potential as an
      anticancer agent by inducing cancer cell death via membrane disruption;
      meanwhile, their intrinsic selectivity renders them as having low cytotoxicity
      towards noncancerous cells. Here, we report the use of a cationic peptide
      amphiphile (PA), named PAH6, to load doxorubicin (Dox) that is intercalated in an
      ATP-binding aptamer-incorporated DNA scaffold. The PA contains a cationic lytic
      sequence, (KLAKLAK)2, a polyhistidine segment for the "proton sponge" effect, and
      a hydrophobic alkyl tail to drive the self-assembly. Dox-loaded DNA was found to
      form a spherical nanocomplex (NC) with PAH6 with particle sizes below 100 nm at
      various ratios. Since the carrier PAH6 is also a therapeutic agent, the drug
      loadings of the NC reached up to ~86% within the ratios we tested, and Dox was
      released from the NC in an ATP-rich environment. In vitro studies indicate that
      the presence of PAH6 could permeabilize cell membranes and kill cells through
      fast membrane disruption and depolarization of mitochondrial membranes. The
      cytotoxicity tests were conducted using A549 nonsmall cell lung cancer cells and
      NIH-3T3 fibroblast cells. PAH6 showed selectivity towards A549 cells.
      Significantly, the Dox-DNA/PAH6 NC exhibited a synergistic effect against A549
      cells, with the IC50 decreased up to ~90% for Dox and ~69% for PAH6 when compared
      to the IC50 values of the two components, respectively. Furthermore, the
      selectivity of PAH6 conferred to the complex an improved therapeutic index
      between A549 and NIH-3T3 cells. A 3D-cultured A549 spheroid model was adopted to
      test the capability of Dox-DNA/PAH6 for tumor penetration. The PAH6 or Dox
      DNA/PAH6 complex was found to break the spheroids into pieces, while Dox-treated
      spheroids maintained their shapes. In summary, this work provides a new strategy
      for constructing nanomedicines using therapeutic agents to meet the features
      required by anticancer treatment.

PMID- 30223513
TI  - Plasma Membrane Lipid Domains as Platforms for Vesicle Biogenesis and Shedding?
AB  - Extracellular vesicles (EVs) contribute to several pathophysiological processes
      and appear as emerging targets for disease diagnosis and therapy. However,
      successful translation from bench to bedside requires deeper understanding of
      EVs, in particular their diversity, composition, biogenesis and shedding
      mechanisms. In this review, we focus on plasma membrane-derived microvesicles
      (MVs), far less appreciated than exosomes. We integrate documented mechanisms
      involved in MV biogenesis and shedding, focusing on the red blood cell as a
      model. We then provide a perspective for the relevance of plasma membrane lipid
      composition and biophysical properties in microvesiculation on red blood cells
      but also platelets, immune and nervous cells as well as tumor cells. Although
      only a few data are available in this respect, most of them appear to converge to
      the idea that modulation of plasma membrane lipid content, transversal asymmetry
      and lateral heterogeneity in lipid domains may play a significant role in the
      vesiculation process. We suggest that lipid domains may represent platforms for
      inclusion/exclusion of membrane lipids and proteins into MVs and that MVs could
      originate from distinct domains during physiological processes and disease
      evolution.

PMID- 30223520
TI  - Diagnosis on Transport Risk Based on a Combined Assessment of Road Accidents and
      Watershed Vulnerability to Spills of Hazardous Substances.
AB  - Roads play an important role in the economic development of cities and regions,
      but the transport of cargo along highways may represent a serious environmental
      problem because a large portion of transported goods is composed of dangerous
      products. In this context, the development and validation of risk management
      tools becomes extremely important to support the decision-making of people and
      agencies responsible for the management of road enterprises. In the present
      study, a method for determination of environmental vulnerability to road spills
      of hazardous substances is coupled with accident occurrence data in a highway,
      with the purpose to achieve a diagnosis on soil and water contamination risk and
      propose prevention measures and emergency alerts. The data on accident
      occurrences involving hazardous and potentially harmful products refer to the
      highway BR 050, namely the segment between the Brazilian municipalities of
      Uberaba and Uberlandia. The results show that many accidents occurred where
      vulnerability is high, especially in the southern sector of the segment,
      justifying the implementation of prevention and alert systems. The coupling of
      vulnerability and road accident data in a geographic information system proved
      efficient in the preparation of quick risk management maps, which are essential
      for alert systems and immediate environmental protection. Overall, the present
      study contributes with an example on how the management of risk can be conducted
      in practice when the transport of dangerous substances along roads is the focus
      problem.

PMID- 30223521
TI  - Dental-Dam for Infection Control and Patient Safety during Clinical Endodontic
      Treatment: Preferences of Dental Patients.
AB  - BACKGROUND: A number of factors (first experience, treating clinician and time to
      place dental-dam) may influence patients' preferences regarding dental-dams. In
      general, patients accept placing it and that it must be used for teeth isolation
      during endodontic procures for the sake of patient safety and infection control.
      OBJECTIVES: The aim of this study is to investigate preferences and experiences
      of patients using dental-dam (DD) isolation during root canal treatment (RCT) and
      to explore influencing factors among the residents of Madinah Munnawara, Saudi
      Arabia. METHODS: Following an ethical approval and a pilot study, a self
      administrated questionnaire was distributed to 305 patients attending endodontic
      clinics at the Taibah University College of Dentistry (TUCOD) over six months.
      Patients voluntarily participated in the study after understanding the
      methodologies and signing a consent form. They were asked to fill out a
      questionnaire on their experiences and preferences in placing the DD during RCT.
      Data were analyzed using the Chi-square test at p = 0.05. RESULTS: The response
      rate was 91%. There was no significant correlation between patients' preferences
      and their race, age and gender (p > 0.05). The majority of participants (74.3%)
      would prefer to use a DD in their next session (p < 0.001). This preference
      negatively correlated with the time required to place a DD and the duration of
      the current visit (p < 0.001). While most of those who would prefer to use a DD
      in their next visit were pleased with how it was placed in the current session
      (76.6%), most of those who would not do so (66.7%) were uncomfortable. Overall,
      the highest proportion of participants (40.2%) reported that prevention of
      instrument swallowing was the most important advantage of DD isolation (p <
      0.001). CONCLUSIONS: Overall, DD isolation for RCT is generally well accepted by
      patients regardless of their country of origin, gender, education and awareness
      of its advantages. Patients' safety was the most attractive advantage for
      patients to the application of the DD. The time required to place the dental dam
      and first visit experience in placing the DD affect patients' future preference.

PMID- 30223519
TI  - Nanoparticles as a Solution for Eliminating the Risk of Mycotoxins.
AB  - Mycotoxins are toxic secondary metabolites produced by certain filamentous fungi.
      The occurrence of mycotoxins in food and feed causes negative health impacts on
      both humans and animals. Clay binders, yeast cell walls, or antioxidant additives
      are the most widely used products for mycotoxin elimination to reduce their
      impact. Although conventional methods are constantly improving, current research
      trends are looking for innovative solutions. Nanotechnology approaches seem to be
      a promising, effective, and low-cost way to minimize the health effects of
      mycotoxins. This review aims to shed light on the critical knowledge gap in
      mycotoxin elimination by nanotechnology. There are three main strategies: mold
      inhibition, mycotoxin adsorption, and reducing the toxic effect via
      nanoparticles. One of the most promising methods is the use of carbon-based
      nanomaterials. Graphene has been shown to have a huge surface and high binding
      capacity for mycotoxins. Attention has also been drawn to polymeric
      nanoparticles; they could substitute adsorbents or enclose any substance, which
      would improve the health status of the organism. In light of these findings, this
      review gives new insights into possible future research that might overcome
      challenges associated with nanotechnology utilization for mycotoxin elimination
      from agricultural products.

PMID- 30223523
TI  - A Comprehensive Calibration Method for a Star Tracker and Gyroscope Units
      Integrated System.
AB  - The integration of a star tracker and gyroscope units (GUs) can take full
      advantage of the benefits of each, and provide continuous and accurate attitude
      information with a high update rate. The systematic error calibration of the
      integrated system is a crucial step to guarantee its attitude accuracy. In this
      paper, a comprehensive calibration method for the star tracker and GUs integrated
      system is proposed from a global perspective. Firstly, the observation model of
      the predicted star centroid error (PSCE) with respect to the systematic errors
      including the star tracker intrinsic parameter errors, GUs errors and fixed angle
      errors is accurately established. Then, the systematic errors are modeled by a
      series of differential equations, based on which the state-space model is
      established. Finally, the systematic errors are decoupled and estimated by a
      Kalman filter according to the established state-space model and observation
      model. The coupling between the errors of the principal point and subcomponents
      of the fixed angles (i.e., Psi x and Psi y ) is analysed. Both simulations and
      experiments indicate that the proposed method is effective at estimating the
      systematic errors of the star tracker and GUs integrated system with high
      accuracy and robustness with respect to different star centroid accuracies and
      gyroscope noise levels.

PMID- 30223522
TI  - Ultra-Small Pd(0) Nanoparticles into a Designed Semisynthetic Lipase: An
      Efficient and Recyclable Heterogeneous Biohybrid Catalyst for the Heck Reaction
      under Mild Conditions.
AB  - A novel heterogeneous enzyme-palladium (Pd) (0) nanoparticles (PdNPs)
      bionanohybrid has been synthesized by an efficient, green, and straightforward
      methodology. A designed Geobacillus thermocatenulatus lipase (GTL) variant
      genetically and then chemically modified by the introduction of a tailor-made
      cysteine-containing complementary peptide- was used as the stabilizing and
      reducing agent for the in situ formation of ultra-small PdNPs nanoparticles
      embedded on the protein structure. This bionanohybrid was an excellent catalyst
      in the synthesis of trans-ethyl cinnamate by Heck reaction at 65  degrees C. It
      showed the best catalytic performance in dimethylformamide (DMF) containing 10
      25% of water as a solvent but was also able to catalyze the reaction in pure DMF
      or with a higher amount of water as co-solvent. The recyclability and stability
      were excellent, maintaining more than 90% of catalytic activity after five cycles
      of use.

PMID- 30223524
TI  - Spatholobus suberectus Ameliorates Diabetes-Induced Renal Damage by Suppressing
      Advanced Glycation End Products in db/db Mice.
AB  - Spatholobus suberectus (SS) is a medicinal herb commonly used in Asia to treat
      anemia, menoxenia and rheumatism. However, its effect of diabetes-induced renal
      damage and mechanisms of action against advanced glycation end-products (AGEs)
      are unclear. In this study, we evaluated the effects of SS on diabetes-induced
      renal damage and explored the possible underlying mechanisms using db/db type 2
      diabetes mice. db/db mice were administered SS extract (50 mg/kg) orally for 6
      weeks. SS-treated group did not change body weight, blood glucose and glycated
      hemoglobin (HbA1c) levels. However, SS treatment reversed diabetes-induced
      dyslipidemia and urinary albumin/creatinine ratio in db/db mice. Moreover, SS
      administration showed significantly increased protein expression of nuclear
      factor erythroid 2-related factor 2 (Nrf2), which is a transcription factor for
      antioxidant enzyme. SS significantly upregulated glyoxalase 1 (Glo1) and NADPH
      quinine oxidoreductase 1 (NQO1) expression but reduced CML accumulation and
      downregulated receptor for AGEs (RAGE). Furthermore, SS showed significant
      decrease of periodic acid-Schiff (PAS)-positive staining and AGEs accumulation in
      histological and immunohistochemical analyses of kidney tissues. Taken together,
      we concluded that SS ameliorated the renal damage by inhibiting diabetes-induced
      glucotoxicity, dyslipidemia and oxidative stress, through the Nrf2/antioxidant
      responsive element (ARE) stress-response system.

PMID- 30223525
TI  - Source Coding Options to Improve HEVC Video Streaming in Vehicular Networks.
AB  - Video delivery in Vehicular Ad-hoc NETworks has a great number of applications.
      However, multimedia streaming over this kind of networks is a very challenging
      issue because (a) it is one of the most resource-demanding applications; (b) it
      requires high bandwidth communication channels; (c) it shows moderate to high
      node mobility patterns and (d) it is common to find high communication
      interference levels that derive in moderate to high loss rates. In this work, we
      present a simulation framework based on OMNeT++ network simulator, Veins
      framework, and the SUMO mobility traffic simulator that aims to study, evaluate,
      and also design new techniques to improve video delivery over Vehicular Ad-hoc
      NETworks. Using the proposed simulation framework we will study different coding
      options, available at the HEVC video encoder, that will help to improve the
      perceived video quality in this kind of networks. The experimental results show
      that packet losses significantly reduce video quality when low interference
      levels are found in an urban scenario. By using different INTRA refresh options
      combined with appropriate tile coding, we will improve the resilience of HEVC
      video delivery services in VANET urban scenarios.

PMID- 30223526
TI  - Diet: Cause or Consequence of the Microbial Profile of Cholelithiasis Disease?
AB  - Recent dietary habits and lifestyle could explain the shaping of the gut
      microbiota composition and, in consequence, the increasing prevalence of certain
      pathologies. However, little attention has been paid to the influence of diet on
      microbiotas, other than the gut microbiota. This is important in cholelithiasis,
      given that changes in the production of bile acids may affect gallbladder
      microbial communities. Our aim was to assess the association between regular
      dietary intake and gallbladder microbial composition. Fourteen adults with
      cholelithiasis and 14 controls, sex-age-matched and without gastrointestinal
      pathology, were included. Diet was assessed through a food frequency
      questionnaire and quantification of gallbladder microbiota sequences by Illumina
      16S rRNA gene-based analysis. The cholelithiasic patients showed greater intake
      of potatoes and lower consumption of vegetables, non-alcoholic drinks, and
      sauces, which resulted in a lower intake of energy, lipids, digestible
      polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic
      compounds. Regarding the altered bile microorganisms in cholelithiasic patients,
      dairy product intake was negatively associated with the proportions of
      Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty
      acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae,
      Propionibacteraceae, Bacteroides, and Escherichia-Shigella. These results support
      a link between diet, biliary microbiota, and cholelithiasis.

PMID- 30223527
TI  - Dry Sliding Wear Behavior and Mild-Severe Wear Transition of Mg97Zn1Y2 Alloy at
      Elevated Temperatures.
AB  - Dry sliding wear behavior of Mg97Zn1Y2 alloy was investigated at test
      temperatures of 50-200  degrees C under three sliding speeds of 0.8 m/s, 3.0 m/s
      and 4.0 m/s. The wear mechanisms in mild and severe wear regimes were identified
      by examination of morphologies and compositions of worn surfaces using scanning
      electron microscope (SEM) and energy dispersive X-ray spectrometer (EDS), and
      from which wear transition maps under different sliding speeds were constructed
      on rectangular coordinate systems with applied load versus test temperature axes.
      It is found that under each sliding speed condition, mild-severe transition load
      decreases almost linearly within the test temperature range of 50  degrees C to
      200  degrees C. Microstructure observation and hardness measurement in
      subsurfaces identify that the softening effect generating form dynamic
      crystallization (DRX) is the dominant mechanism for the mild-severe wear
      transition at elevated temperatures. The mild-severe wear transition at 50-200 
      degrees C follows the contact surface DRX temperature criterion, and the
      transition loads can be well evaluated using the criterion.

PMID- 30223528
TI  - miRmapper: A Tool for Interpretation of miRNA-mRNA Interaction Networks.
AB  - It is estimated that 30% of all genes in the mammalian cells are regulated by
      microRNA (miRNAs). The most relevant miRNAs in a cellular context are not
      necessarily those with the greatest change in expression levels between healthy
      and diseased tissue. Differentially expressed (DE) miRNAs that modulate a large
      number of messenger RNA (mRNA) transcripts ultimately have a greater influence in
      determining phenotypic outcomes and are more important in a global biological
      context than miRNAs that modulate just a few mRNA transcripts. Here, we describe
      the development of a tool, "miRmapper", which identifies the most dominant miRNAs
      in a miRNA-mRNA network and recognizes similarities between miRNAs based on
      commonly regulated mRNAs. Using a list of miRNA-target gene interactions and a
      list of DE transcripts, miRmapper provides several outputs: (1) an adjacency
      matrix that is used to calculate miRNA similarity utilizing the Jaccard distance;
      (2) a dendrogram and (3) an identity heatmap displaying miRNA clusters based on
      their effect on mRNA expression; (4) a miRNA impact table and (5) a barplot that
      provides a visual illustration of this impact. We tested this tool using
      nonmetastatic and metastatic bladder cancer cell lines and demonstrated that the
      most relevant miRNAs in a cellular context are not necessarily those with the
      greatest fold change. Additionally, by exploiting the Jaccard distance, we
      unraveled novel cooperative interactions between miRNAs from independent families
      in regulating common target mRNAs; i.e., five of the top 10 miRNAs act in
      synergy.

PMID- 30223529
TI  - Association between Cigarette Smoking Status and Composition of Gut Microbiota:
      Population-Based Cross-Sectional Study.
AB  - There have been few large-scale studies on the relationship between smoking and
      gut microbiota. We investigated the relationship between smoking status and the
      composition of gut microbiota. This was a population-based cross-sectional study
      using Healthcare Screening Center cohort data. A total of 758 men were selected
      and divided into three groups: never (n = 288), former (n = 267), and current
      smokers (n = 203). Among the three groups, there was no difference in alpha
      diversity, however, Jaccard-based beta diversity showed significant difference (p
      = 0.015). Pairwise permutational multivariate analysis of variance (PERMANOVA)
      tests between never and former smokers did not show a difference; however, there
      was significant difference between never and current smokers (p = 0.017) and
      between former and current smokers (p = 0.011). Weighted UniFrac-based beta
      diversity also showed significant difference among the three groups (p = 0.038),
      and pairwise PERMANOVA analysis of never and current smokers showed significant
      difference (p = 0.01). In the analysis of bacterial composition, current smokers
      had an increased proportion of the phylum Bacteroidetes with decreased Firmicutes
      and Proteobacteria compared with never smokers, whereas there were no differences
      between former and never smokers. In conclusion, gut microbiota composition of
      current smokers was significantly different from that of never smokers.
      Additionally, there was no difference in gut microbiota composition between never
      and former smokers.

PMID- 30223531
TI  - Cross-Voting SVM Method for Multiple Vehicle Classification in Wireless Sensor
      Networks.
AB  - A novel multi-class classification method named the voting-cross support vector
      machine (SVM) method was proposed in this study, for classifying vehicle targets
      in wireless sensor networks. The advantages and disadvantages of available
      methods were summarized, after a comparative analysis of commonly used multi
      objective classification algorithms. To improve the classification accuracy of
      multi-class classification and ensure the low complexity of the algorithm for
      engineering implementation on wireless sensor network (WSN) nodes, a framework
      was proposed for cross-matching and voting on the category to which the vehicle
      belongs after combining the advantages of the directed acyclic graph SVM (DAGSVM)
      method and binary-tree SVM method. The SVM classifier was selected as the basis
      two-class classifier in the framework, after comparing the classification
      performance of several commonly used methods. We utilized datasets acquired from
      a real-world experiment to validate the proposed method. The calculated results
      demonstrated that the cross-voting SVM method could effectively increase the
      classification accuracy for the classification of multiple vehicle targets, with
      a limited increase in the algorithm complexity. The application of the cross
      voting SVM method effectively improved the target classification accuracy (by
      approximately 7%), compared with the DAGSVM method and the binary-tree SVM
      method, whereas time consumption decreased by approximately 70% compared to the
      DAGSVM method.

PMID- 30223530
TI  - TRPC6 Channels Are Required for Proliferation, Migration and Invasion of Breast
      Cancer Cell Lines by Modulation of Orai1 and Orai3 Surface Exposure.
AB  - Transient receptor potential channels convey signaling information from a number
      of stimuli to a wide variety of cellular functions, mainly by inducing changes in
      cytosolic Ca2+ concentration. Different members of the TRPC, TRPM and TRPV
      subfamilies have been reported to play a role in tumorigenesis. Here we show that
      the estrogen receptor positive and triple negative breast cancer cell lines, MCF7
      and MDA-MB-231, respectively, exhibit enhanced expression of the TRPC6 channel as
      compared to the non-tumoral MCF10A cell line. In vitro TRPC6 knockdown using
      shRNA impaired MCF7 and MDA-MB-231 cell proliferation, migration and invasion
      detected by BrdU incorporation, wound healing and Boyden chamber assays,
      respectively. Using RNAi-mediated TRPC6 silencing as well as overexpression of
      the pore-dead dominant-negative TRPC6 mutant we have found that TRPC6 plays a
      relevant role in the activation of store-operated Ca2+ entry in the breast cancer
      cell lines but not in non-tumoral breast cells. Finally, we have found that TRPC6
      interacts with Orai1 and Orai3 in MCF7 and MDA-MB-231 cells and is required for
      the translocation of Orai1 and Orai3 to the plasma membrane in MDA-MB-231 and
      MCF7 cells, respectively, upon Ca2+ store depletion. These findings introduce a
      novel mechanism for the modulation of Ca2+ influx and the development of
      different cancer hallmarks in breast cancer cells.

PMID- 30223532
TI  - Gastric Emptying and Dynamic In Vitro Digestion of Drinkable Yogurts: Effect of
      Viscosity and Composition.
AB  - Gastric emptying of food is mainly driven by the caloric concentration, the
      rheological properties of the chyme, and the physical state (liquid/solid) of
      food once in the stomach. The present work investigated: (1) The effect of the
      composition and the viscosity of drinkable yogurts on gastric emptying in pigs,
      and (2) the behavior of yogurts during dynamic in vitro digestion. Three
      isocaloric liquid yogurts were manufactured: Two enriched in protein and fiber
      showing either a low (LV) or high (HV) viscosity, one control enriched in sugar
      and starch (CT). They were labelled with 99mTc-sulfur colloid and given to pigs
      (n = 11) to determine gastric emptying pattern by gamma scintigraphy. Then
      dynamic in vitro digestion of the yogurts was done using the parameters of
      gastric emptying determined in vivo. Gastric emptying half-times were
      significantly longer for LV than CT, whereas HV exhibited an intermediate
      behavior. In vitro gastric digestion showed a quick hydrolysis of caseins,
      whereas whey proteins were more resistant in the stomach particularly for LV and
      HV. During the intestinal phase, both whey proteins and caseins were almost fully
      hydrolyzed. Viscosity was shown to affect the behavior of yogurt in the small
      intestine.

PMID- 30223533
TI  - Rational Use of Medicines in Neonates: Current Observations, Areas for Research
      and Perspectives.
AB  - A focused reflection on rational medicines use in neonates is valuable and
      relevant, because indicators to assess rational medicines use are difficult to
      apply to neonates. Polypharmacy and exposure to antibiotics are common, while
      dosing regimens or clinical guidelines are only rarely supported by robust
      evidence in neonates. This is at least in part due to the extensive variability
      in pharmacokinetics and subsequent effects of medicines in neonates. Medicines
      utilization research informs us on trends, on between unit variability and on the
      impact of guideline implementation. We illustrate these aspects using data on
      drugs for gastroesophageal reflux, analgesics or anti-epileptic drugs. Areas for
      additional research are drug-related exposure during breastfeeding (exposure
      prediction) and how to assess safety (tools to assess seriousness, causality, and
      severity tailored to neonates) since both efficacy and safety determine rational
      drug use. To further improve rational medicines use, we need more data and tools
      to assess efficacy and safety in neonates. Moreover, we should facilitate access
      to such data, and explore strategies for effective implementation. This is
      because prescription practices are not only rational decisions, but also have
      psychosocial aspects that may guide clinicians to irrational practices, in part
      influenced by the psychosocial characteristics of this population.

PMID- 30223534
TI  - Dietary Deoxynivalenol (DON) May Impair the Epithelial Barrier and Modulate the
      Cytokine Signaling in the Intestine of Atlantic Salmon (Salmo salar).
AB  - Impaired growth, immunity, and intestinal barrier in mammals, poultry, and carp
      have been attributed to the mycotoxin deoxynivalenol (DON). The increased use of
      plant ingredients in aquaculture feed implies a risk for contamination with
      mycotoxins. The effects of dietary DON were explored in 12-month-old Atlantic
      salmon (Salmo salar) (start weight of 58 g) that were offered a standard feed
      with non-detectable levels of mycotoxins (control group) or 5.5 mg DON/kg feed
      (DON group). Each group comprised two tanks with 25 fish per tank. Five fish from
      each tank were sampled eight weeks after the start of the feeding trial, when
      mean weights for the control and DON groups were 123.2 g and 80.2 g,
      respectively. The relative expression of markers for three tight junction
      proteins (claudin 25b, occludin, and tricellulin) were lower, whereas the
      relative expression of a marker for proliferating cell nuclear antigen was higher
      in both the mid-intestine and the distal intestine in fish fed DON compared with
      fish from the control group. The relative expression of markers for two
      suppressors of cytokine signaling (SOCS1 and SOCS2) were higher in the distal
      intestine in fish fed DON. There was no indication of inflammation attributed to
      the feed in any intestinal segments. Our findings suggest that dietary DON
      impaired the intestinal integrity, while an inflammatory response appeared to be
      mitigated by suppressors of cytokine signaling. A dysfunctional intestinal
      barrier may have contributed to the impaired production performance observed in
      the DON group.

PMID- 30223535
TI  - Human Motion Recognition by Textile Sensors Based on Machine Learning Algorithms.
AB  - Wearable sensors for human physiological monitoring have attracted tremendous
      interest from researchers in recent years. However, most of the research involved
      simple trials without any significant analytical algorithms. This study provides
      a way of recognizing human motion by combining textile stretch sensors based on
      single-walled carbon nanotubes (SWCNTs) and spandex fabric (PET/SP) and machine
      learning algorithms in a realistic application. In the study, the performance of
      the system will be evaluated by identification rate and accuracy of the motion
      standardized. This research aims to provide a realistic motion sensing wearable
      product without unnecessary heavy and uncomfortable electronic devices.

PMID- 30223537
TI  - Exploiting Fine-Grained Subcarrier Information for Device-Free Localization in
      Wireless Sensor Networks.
AB  - Device-free localization (DFL) that aims to localize targets without carrying any
      electronic devices is addressed as an emerging and promising research topic. DFL
      techniques estimate the locations of transceiver-free targets by analyzing their
      shadowing effects on the radio signals that travel through the area of interest.
      Recently, compressive sensing (CS) theory has been applied in DFL to reduce the
      number of measurements by exploiting the inherent spatial sparsity of target
      locations. In this paper, we propose a novel CS-based multi-target DFL method to
      leverage the frequency diversity of fine-grained subcarrier information.
      Specifically, we build the dictionaries of multiple channels based on the saddle
      surface model and formulate the multi-target DFL as a joint sparse recovery
      problem. To estimate the location vector, an iterative location vector estimation
      algorithm is developed under the multitask Bayesian compressive sensing (MBCS)
      framework. Compared with the state-of-the-art CS-based multi-target DFL
      approaches, simulation results validate the superiority of the proposed
      algorithm.

PMID- 30223536
TI  - The Surveillance of Chikungunya Virus in a Temperate Climate: Challenges and
      Possible Solutions from the Experience of Lazio Region, Italy.
AB  - CHIKV has become an emerging public health concern in the temperate regions of
      the Northern Hemisphere as a consequenceof the expansion of the endemic areas of
      its vectors (mainly Aedes aegypti and Aedesalbopictus). In 2017, a new outbreak
      of CHIKV was detected in Italy with three clusters of autochthonous transmission
      in the Lazio Region (central Italy), in the cities of Anzio, Rome, and Latina and
      a secondary cluster in the Calabria Region (south Italy). Given the climate
      characteristics of Italy, sporadic outbreaks mostly driven by imported cases
      followed by autochthonous transmission could occur during the summer season. This
      highlights the importance of a well-designed surveillance system, which should
      promptly identify autochthonous transmission. The use of a surveillance system
      integrating different surveillance tools, including entomological surveillance in
      a one health approach, together with education of the health care professionals
      should facilitate the detection, response, and control of arboviruses spreading.

PMID- 30223538
TI  - Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid
      Leukemia Cells and Its Association with Adverse Prognosis.
AB  - Clonal heterogeneity detected by karyotyping is a biomarker associated with
      adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the
      phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR)
      pathway is present in AML cells, and this pathway integrates signaling from
      several upstream receptors/mediators. We suggest that this pathway reflects
      biologically important clonal heterogeneity. We investigated constitutive PI3K
      Akt-mTOR pathway activation in primary human AML cells derived from 114 patients,
      together with 18 pathway mediators. The cohort included patients with normal
      karyotype or single karyotype abnormalities and with an expected heterogeneity of
      molecular genetic abnormalities. Clonal heterogeneity reflected as pathway
      mediator heterogeneity was detected for 49 patients. Global gene expression
      profiles of AML cell populations with and without clonal heterogeneity differed
      with regard to expression of ectopic olfactory receptors (a subset of G-protein
      coupled receptors) and proteins involved in G-protein coupled receptor signaling.
      Finally, the presence of clonal heterogeneity was associated with adverse
      prognosis for patients receiving intensive antileukemic treatment. The clonal
      heterogeneity as reflected in the activation status of selected mediators in the
      PI3K-Akt-mTOR pathway was associated with a different gene expression profile and
      had an independent prognostic impact. Biological heterogeneity reflected in the
      intracellular signaling status should be further investigated as a prognostic
      biomarker in human AML.

PMID- 30223540
TI  - Liquid Level Sensor Based on a V-Groove Structure Plastic Optical Fiber.
AB  - A high sensitivity and easily fabricated liquid level sensor based on the V
      groove structure plastic optical fiber (POF) was described. In the design, the V
      groove structure on the POF is produced by using a die-press-print method, which
      effectively reduces the complexity of the fabrication process and makes it easier
      for mass production of liquid level sensors. This greatly enhances the usefulness
      of the proposed sensor in cost effective liquid level sensing applications. The
      transmission characteristic of the POF could be changed when the V-groove
      structure was immerged or emerged by the rising or falling liquid. The liquid
      level sensing performances for the sensor probes with different structural
      parameters were investigated, and the sensor performances for the liquids with
      different refractive indices and the sensor dynamic response were also tested.
      Experimental results show that the sensor's sensitivity can reach 0.0698 mm-1,
      with a resolution of 2.5 mm. Results also show that the sensor has a fast
      response time of 920 ms.

PMID- 30223539
TI  - The Effectiveness and Cost-Effectiveness of Hepatitis C Screening for Migrants in
      the EU/EEA: A Systematic Review.
AB  - Chronic hepatitis C (HCV) is a public health priority in the European
      Union/European Economic Area (EU/EEA) and is a leading cause of chronic liver
      disease and liver cancer. Migrants account for a disproportionate number of HCV
      cases in the EU/EEA (mean 14% of cases and >50% of cases in some countries). We
      conducted two systematic reviews (SR) to estimate the effectiveness and cost
      effectiveness of HCV screening for migrants living in the EU/EEA. We found that
      screening tests for HCV are highly sensitive and specific. Clinical trials report
      direct acting antiviral (DAA) therapies are well-tolerated in a wide range of
      populations and cure almost all cases (>95%) and lead to an 85% lower risk of
      developing hepatocellular carcinoma and an 80% lower risk of all-cause mortality.
      At 2015 costs, DAA based regimens were only moderately cost-effective and as a
      result less than 30% of people with HCV had been screened and less 5% of all HCV
      cases had been treated in the EU/EEA in 2015. Migrants face additional barriers
      in linkage to care and treatment due to several patient, practitioner, and health
      system barriers. Although decreasing HCV costs have made treatment more
      accessible in the EU/EEA, HCV elimination will only be possible in the region if
      health systems include and treat migrants for HCV.

PMID- 30223542
TI  - An Image Signal Accumulation Multi-Collection-Gate Image Sensor Operating at 25
      Mfps with 32 * 32 Pixels and 1220 In-Pixel Frame Memory.
AB  - The paper presents an ultra-high-speed image sensor for motion pictures of
      reproducible events emitting very weak light. The sensor is backside-illuminated.
      Each pixel is equipped with multiple collection gates (MCG) at the center of the
      front side. Each collection gate is connected to an in-pixel large memory unit,
      which can accumulate image signals captured by repetitive imaging. The
      combination of the backside illumination, image signal accumulation, and slow
      readout from the in-pixel signal storage after an image capturing operation
      offers a very high sensitivity. Pipeline signal transfer from the the multiple
      collection gates (MCG) to the in-pixel memory units enables the sensor to achieve
      a large frame count and a very high frame rate at the same time. A test sensor
      was fabricated with a pixel count of 32 * 32 pixels. Each pixel is equipped with
      four collection gates, each connected to a memory unit with 305 elements; thus,
      with a total frame count of 1220 (305 * 4) frames. The test camera achieved 25
      Mfps, while the sensor was designed to operate at 50 Mfps.

PMID- 30223544
TI  - Inappropriate Medication Use in Hospitalized Patients Diagnosed with Parkinson's
      Disease.
AB  - The purpose of this study was to evaluate the rate at which potentially
      inappropriate medications were administered for patients diagnosed with
      Parkinson's disease (PD). This is a single-center, retrospective, case cohort
      study with data collected at an academic medical center between January 2010 and
      December 2013. Participants included all adult patients with admission diagnosis
      codes for PD. Included patients were screened for administrations of 27
      potentially inappropriate medications and two potentially appropriate medications
      to be used for comparison. There were 1736 patients who met inclusion criteria
      with 175 documented administrations of potentially inappropriate medications to
      77 patients. Patients who received potentially inappropriate medications had a
      longer mean duration of stay than the baseline population of PD patients (3.3
      days vs. 1.9 days, p-value < 0.001). Despite recommendations to avoid certain
      medications in PD patients, a substantial number of administrations still
      occurred. The use of these medications can have clinical implications and our
      findings demonstrate increases in duration of stay. The findings from this study
      can assist in developing technological alerts to reduce inappropriate prescribing
      to PD patients. Larger prospective studies are warranted to further investigate
      the administration of inappropriate medications to patients diagnosed with PD.

PMID- 30223541
TI  - Long Non-Coding RNAs as Endogenous Target Mimics and Exploration of Their Role in
      Low Nutrient Stress Tolerance in Plants.
AB  - Long non-coding RNA (lncRNA) research in plants has recently gained momentum
      taking cues from studies in animals systems. The availability of next-generation
      sequencing has enabled genome-wide identification of lncRNA in several plant
      species. Some lncRNAs are inhibitors of microRNA expression and have a function
      known as target mimicry with the sequestered transcript known as an endogenous
      target mimic (eTM). The lncRNAs identified to date show diverse mechanisms of
      gene regulation, most of which remain poorly understood. In this review, we
      discuss the role of identified putative lncRNAs that may act as eTMs for nutrient
      responsive microRNAs (miRNAs) in plants. If functionally validated, these
      putative lncRNAs would enhance current understanding of the role of lncRNAs in
      nutrient homeostasis in plants.

PMID- 30223543
TI  - Macronutrient Intake in Relation to Migraine and Non-Migraine Headaches.
AB  - We investigated the association of mean daily macronutrient intake with migraine
      and non-migraine headaches. This cross-sectional study included 8042 men and
      23,728 women from the ongoing population-based NutriNet-Sante e-cohort. Headache
      status was assessed via an online self-report questionnaire (2013-2016). Migraine
      was defined using established criteria and dietary macronutrient intake was
      estimated via >=3 24 h dietary records. Mean daily intake (g/day) of
      carbohydrates (simple, complex, and total), protein, and fat (saturated fatty
      acids, monounsaturated fatty acids, polyunsaturated fatty acids, and total) were
      the main exposure variables. Adjusted gender-specific analysis of variance
      (ANOVA) models were fit. Presence of migraines was noted in 9.2% of men (mean age
      = 54.3 +/- 13.3 years) and 25.7% of women (mean age = 49.6 +/- 12.8 years). In
      adjusted models, we observed (1) somewhat lower protein (p < 0.02) and higher
      total fat (p < 0.01) intake among male migraineurs compared with males without
      headaches and those with non-migraine headaches; (2) somewhat higher total fat (p
      < 0.0001) and total carbohydrate intake (p < 0.05) among female migraineurs
      compared with females without headaches and those with non-migraine headaches.
      The findings, which provide preliminary support for modest gender-specific
      differences in macronutrient intake by migraine status, merit confirmation in
      different population-based settings, as well as longitudinally, and could help to
      inform future dietary interventions in headache prevention.

PMID- 30223545
TI  - Effects of a Si-doped InGaN Underlayer on the Optical Properties of InGaN/GaN
      Quantum Well Structures with Different Numbers of Quantum Wells.
AB  - In this paper we report on the optical properties of a series of InGaN polar
      quantum well structures where the number of wells was 1, 3, 5, 7, 10 and 15 and
      which were grown with the inclusion of an InGaN Si-doped underlayer. When the
      number of quantum wells is low then the room temperature internal quantum
      efficiency can be dominated by thermionic emission from the wells. This can occur
      because the radiative recombination rate in InGaN polar quantum wells can be low
      due to the built-in electric field across the quantum well which allows the
      thermionic emission process to compete effectively at room temperature limiting
      the internal quantum efficiency. In the structures that we discuss here, the
      radiative recombination rate is increased due to the effects of the Si-doped
      underlayer which reduces the electric field across the quantum wells. This
      results in the effect of thermionic emission being largely eliminated to such an
      extent that the internal quantum efficiency at room temperature is independent of
      the number of quantum wells.

PMID- 30223546
TI  - Socioeconomic Status in Adolescents: A Study of Its Relationship with Overweight
      and Obesity and Influence on Social Network Configuration.
AB  - Socioeconomic status (SES) influences all the determinants of health,
      conditioning health throughout life. The aim of the present study was to explore
      the relationship between socioeconomic status and obesity in adolescence through
      an analysis of the patterns of contact between peers as a function of this
      parameter. A cross-sectional study was performed, analyzing a sample of 235
      students aged 14 to 18 and 11 class networks. Social network analysis was used to
      analyze structural variables of centrality from a sociocentric perspective. We
      found that adolescents with a medium-low SES presented a two-fold higher
      probability of being overweight, but we did not detect any differences in the
      configuration of their social networks when compared with those of normal-weight
      adolescents. However, we did find significant differences in the formation of
      networks according to SES in the overall sample and disaggregated by gender,
      whereby adolescents with a high SES in general presented a higher capacity to
      form wider social networks. Elucidating the relationship between SES and
      overweight and its influence on social network formation can contribute to the
      design of preventative strategies against overweight and obesity in adolescents,
      since their social environment can provide them with several resources to combat
      excess weight.

PMID- 30223547
TI  - Diagnosis of Newly Delivered Mothers for Periodontitis with a Novel Oral-Rinse
      aMMP-8 Point-of-Care Test in a Rural Malawian Population.
AB  - A novel qualitative point-of-care test of activated matrix metalloproteinase-8
      (aMMP-8) using noninvasive oral rinse sampling procedures has been developed for
      the early detection of collagen breakdown indicating periodontal tissue
      destruction. The main object of this study was to assess the reliability of the
      test in a low-income setting to identify participants with history of periodontal
      destruction detected as alveolar bone loss (ABL) in radiographs. This cross
      sectional study included 486 women who had recently delivered in rural Malawi.
      The aMMP-8 test and dental panoramic radiographs were taken within 48 h of
      delivery. The performance of the test in comparison to radiological examinations
      was tested by following the standards for reporting of diagnostic accuracy
      studies protocol (STARD) with respective statistical measures and 95% confidence
      intervals. From the 486 eligible participants, 461 mothers with complete data,
      aged from 15 to 46 years (mean 24.8, SD 6.0) were included in the analysis. ABL
      was identified in 116 of 461 participants. There was 56% agreement between the
      aMMP-8 test results and detected ABL (yes or no) in radiographs. Calculated
      sensitivity of the test was 80% (72-87%), specificity 48% (43-54%), positive
      predictive value 34% (31-37%), negative predictive value 88% (83-91%), positive
      likelihood ratio 1.55 (1.35-1.77), and negative likelihood ratio 0.41(0.28-0.60).
      The aMMP-8 test sensitivity and negative predictive value to identify the ABL
      cases were relatively high, but there was additionally a high rate of test
      positive results in participants without ABL, especially in young mothers,
      leading to low overall agreement between the test results and radiological bone
      loss. Further longitudinal studies are needed to examine if the test positive
      subjects are in risk of future bone loss before the detectable signs of
      periodontitis in radiographs.

PMID- 30223549
TI  - A Room Temperature VOCs Gas Sensor Based on a Layer by Layer Multi-Walled Carbon
      Nanotubes/Poly-ethylene Glycol Composite.
AB  - Sensitive detection of volatile organic compounds (VOCs) is significant for
      environmental monitoring and medical applications. In this work, multi-walled
      carbon nanotubes (MWCNTs) and polyethylene glycol (PEG) that have good adsorption
      for VOCs, were sprayed layer by layer on an interdigitated electrode (IDE) to
      build a sensitive VOCs gas sensor. The relative resistance change (?R/R) when the
      sensor was exposed to VOCs was measured. The sensor showed high sensitivity to
      acetone, ethanol, isopropanol and isoprene with fast response (110 +/- 5 s) and
      recovery (152 +/- 5 s) at room temperature, and the lower detection limit (LDL)
      of the sensor reached 9 ppm. With the micro-fabricated IDE structure, the sensor
      can be easily built into an electric nose for VOC recognition and measurement.

PMID- 30223548
TI  - PCB11 Metabolite, 3,3'-Dichlorobiphenyl-4-ol, Exposure Alters the Expression of
      Genes Governing Fatty Acid Metabolism in the Absence of Functional Sirtuin 3:
      Examining the Contribution of MnSOD.
AB  - Although the production of polychlorinated biphenyls (PCBs) is prohibited, the
      inadvertent production of certain lower-chlorinated PCB congeners still threatens
      human health. We and others have identified 3,3'-dichlorobiphenyl (PCB11) and its
      metabolite, 3,3'-dichlorobiphenyl-4-ol (4OH-PCB11), in human blood, and there is
      a correlation between exposure to this metabolite and mitochondrial oxidative
      stress in mammalian cells. Here, we evaluated the downstream effects of 4OH-PCB11
      on mitochondrial metabolism and function in the presence and absence of
      functional Sirtuin 3 (SIRT3), a mitochondrial fidelity protein that protects
      redox homeostasis. A 24 h exposure to 3 MUM 4OH-PCB11 significantly decreased the
      cellular growth and mitochondrial membrane potential of SIRT3-knockout mouse
      embryonic fibroblasts (MEFs). Only wild-type cells demonstrated an increase in
      Manganese superoxide dismutase (MnSOD) activity in response to 4OH-PCB11-induced
      oxidative injury. This suggests the presence of a SIRT3-mediated post
      translational modification to MnSOD, which was impaired in SIRT3-knockout MEFs,
      which counters the PCB insult. We found that 4OH-PCB11 increased mitochondrial
      respiration and endogenous fatty-acid oxidation-associated oxygen consumption in
      SIRT3-knockout MEFs; this appeared to occur because the cells exhausted their
      reserve respiratory capacity. To determine whether these changes in mitochondrial
      respiration were accompanied by similar changes in the regulation of fatty acid
      metabolism, we performed quantitative real-time polymerase chain reaction (qRT
      PCR) after a 24 h treatment with 4OH-PCB11. In SIRT3-knockout MEFs, 4OH-PCB11
      significantly increased the expression of ten genes controlling fatty acid
      biosynthesis, metabolism, and transport. When we overexpressed MnSOD in these
      cells, the expression of six of these genes returned to the baseline level,
      suggesting that the protective role of SIRT3 against 4OH-PCB11 is partially
      governed by MnSOD activity.

PMID- 30223550
TI  - Specialized Living Wound Dressing Based on the Self-Assembly Approach of Tissue
      Engineering.
AB  - There is a high incidence of failure and recurrence for chronic skin wounds
      following conventional therapies. To promote healing, the use of skin substitutes
      containing living cells as wound dressings has been proposed. The aim of this
      study was to produce a scaffold-free cell-based bilayered tissue-engineered skin
      substitute (TES) containing living fibroblasts and keratinocytes suitable for use
      as wound dressing, while considering production time, handling effort during the
      manufacturing process, and stability of the final product. The self-assembly
      method, which relies on the ability of mesenchymal cells to secrete and organize
      connective tissue sheet sustaining keratinocyte growth, was used to produce TESs.
      Three fibroblast-seeding densities were tested to produce tissue sheets. At day
      17, keratinocytes were added onto 1 or 3 (reference method) stacked tissue
      sheets. Four days later, TESs were subjected either to 4, 10, or 17 days of
      culture at the air-liquid interface (A/L). All resulting TESs were comparable in
      terms of their histological aspect, protein expression profile and contractile
      behavior in vitro. However, signs of extracellular matrix (ECM) digestion that
      progressed over culture time were noted in TESs produced with only one fibroblast
      derived tissue sheet. With lower fibroblast density, the ECM of TESs was almost
      completely digested after 10 days A/L and lost histological integrity after
      grafting in athymic mice. Increasing the fibroblast seeding density 5 to 10 times
      solved this problem. We conclude that the proposed method allows for a 25-day
      production of a living TES, which retains its histological characteristics in
      vitro for at least two weeks.

PMID- 30223551
TI  - Detecting and Visualizing Outliers in Provider Profiling Using Funnel Plots and
      Mixed Effects Models-An Example from Prescription Claims Data.
AB  - When prescribing a drug for a patient, a physician also has to consider economic
      aspects. We were interested in the feasibility and validity of profiling based on
      funnel plots and mixed effect models for the surveillance of German ambulatory
      care physicians' prescribing. We analyzed prescriptions issued to patients with a
      health insurance card attending neurologists' and psychiatrists' ambulatory
      practices in the German federal state of Saarland. The German National
      Association of Statutory Health Insurance Physicians developed a prescribing
      assessment scheme (PAS) which contains a systematic appraisal of the benefit of
      drugs for so far 12 different indications. The drugs have been classified on the
      basis of their clinical evidence as "standard", "reserve" or "third level"
      medication. We had 152.583 prescriptions in 56 practices available for analysis.
      A total of 38.796 patients received these prescriptions. The funnel plot approach
      with additive correction for overdispersion was almost equivalent to a mixed
      effects model which directly took the multilevel structure of the data into
      account. In the first case three practices were labeled as outliers, the mixed
      effects model resulted in two outliers. We suggest that both techniques should be
      routinely applied within a surveillance system of prescription claims data.

PMID- 30223552
TI  - Mind the Gap: Mapping Mass Spectral Databases in Genome-Scale Metabolic Networks
      Reveals Poorly Covered Areas.
AB  - The use of mass spectrometry-based metabolomics to study human, plant and
      microbial biochemistry and their interactions with the environment largely
      depends on the ability to annotate metabolite structures by matching mass
      spectral features of the measured metabolites to curated spectra of reference
      standards. While reference databases for metabolomics now provide information for
      hundreds of thousands of compounds, barely 5% of these known small molecules have
      experimental data from pure standards. Remarkably, it is still unknown how well
      existing mass spectral libraries cover the biochemical landscape of prokaryotic
      and eukaryotic organisms. To address this issue, we have investigated the
      coverage of 38 genome-scale metabolic networks by public and commercial mass
      spectral databases, and found that on average only 40% of nodes in metabolic
      networks could be mapped by mass spectral information from standards. Next, we
      deciphered computationally which parts of the human metabolic network are poorly
      covered by mass spectral libraries, revealing gaps in the eicosanoids, vitamins
      and bile acid metabolism. Finally, our network topology analysis based on the
      betweenness centrality of metabolites revealed the top 20 most important
      metabolites that, if added to MS databases, may facilitate human metabolome
      characterization in the future.

PMID- 30223553
TI  - Aggregation-Induced Emission of Tetraphenylethene-Conjugated Phenanthrene
      Derivatives and Their Bio-Imaging Applications.
AB  - In this study, a series of rationally designed emissive phenanthrene derivatives
      were synthesized and their aggregation-induced emission (AIE) properties in
      tetrahydrofuran (THF)/water mixtures were investigated. Two tetraphenylethene
      (TPE) segments were conjugated to both ends of the phenanthrene core at the para
      positions and meta-positions, resulting in pTPEP and mTPEP derivatives,
      respectively. While the TPE-conjugated phenanthrene derivatives did not show any
      emission when dissolved in pure THF, they showed strong sky-blue emissions in
      water-THF mixtures, which is attributed to the restriction of intramolecular
      motions of TPE segments by aggregation. Furthermore, silica nanoparticles loaded
      with these AIE-active compounds were prepared and proved to be promising
      intracellular imaging agents.

PMID- 30223554
TI  - Susceptibility Testing of Fungi to Antifungal Drugs.
AB  - Susceptibility testing of fungi against antifungal drugs commonly used for
      therapy is a key component of the care of patients with invasive fungal
      infections. Antifungal susceptibility testing (AFST) has progressed in recent
      decades to finally become standardized and available as both Clinical and
      Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial
      Susceptibility Testing (EUCAST) reference methods and in commercial
      manual/automated phenotypic methods. In clinical practice, the Sensititre
      YeastOne and Etest methods are widely used for AFST, particularly for sterile
      site isolates of Candida. Nevertheless, AFST is moving toward new phenotypic
      methods, such as matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF MS), that are capable of providing rapid, and potentially
      more actionable, results for the treating clinician. Our objective is to
      summarize updated data on phenotypic methods for AFST of Candida and Aspergillus
      species and to assess their significance in view of opposing, but emerging,
      molecular genotypic methods.

PMID- 30223555
TI  - Food Insecurity and Cardiovascular Disease Risk Factors among Mississippi Adults.
AB  - Background: Food insecurity is a public health problem. There is limited data on
      food insecurity in Mississippi. Methods: We analyzed data from the 2015
      Mississippi Behavioral Risk Factor Surveillance System, which included the Social
      Context Module for 5870 respondents. Respondents who indicated that in the past
      12 months they were "always", "usually", or "sometimes" "worried or stressed
      about having enough money to buy nutritious meals" were considered food insecure.
      Food insecurity was compared across sociodemographic and health characteristics
      using chi-square tests, and the association between food insecurity and select
      cardiovascular disease risk factors was assessed using logistic regression.
      Results: The prevalence of food insecurity was 42.9%. Compared to the referent
      group, Mississippi adults with high blood pressure had 51% higher odds, those
      with diabetes had 30% higher odds, those who were not physically active had 36%
      higher odds, and those who consumed fewer than five fruits and vegetables daily
      had 50% higher odds of being food insecure. Conclusion: Among Mississippi adults,
      food insecurity is associated with high blood pressure, diabetes, obesity, fruit
      and vegetable consumption, physical inactivity, and smoking.

PMID- 30223556
TI  - The Early Recognition and Management of Sepsis in Sub-Saharan African Adults: A
      Systematic Review and Meta-Analysis.
AB  - Sepsis is a common cause of morbidity and mortality in sub-Saharan African
      adults. Standardised management pathways have been documented to improve the
      survival of adults with sepsis from high-resource settings. Our aim was to assess
      the current evidence base for early sepsis interventions (recognition, empirical
      antibiotics, and resuscitation) in resource-poor settings of sub-Saharan Africa.
      We searched MEDLINE, EMBASE and CINHAL Plus databases to identify interventional
      studies for the early recognition and management of sepsis in sub-Saharan Africa
      (1 January 2000 to 1 August 2018) using a protocol-driven search strategy:
      adults, protocolised care pathway, and sub-Saharan Africa. We identified 725
      publications of which three met criteria for final selection. Meta-analysis from
      two randomised controlled trials demonstrated that mortality was increased by
      'early goal-directed therapy' interventions that increased fluid resuscitation
      (R.R. 1.26, 95% C.I. 1.00-1.58, p = 0.045; I2 53%). The third observational
      cohort study demonstrated improved survival after implementation of protocolised
      management for sepsis (mortality 33.0% vs. 45.7%, p = 0.005). No study
      incorporated standardised protocols for empirical antibiotic administration. High
      rates of pneumonia and mycobacteraemia were reported. There has been little
      research into the early recognition and management of sepsis in sub-Saharan
      Africa. Interventional trials of early goal-directed therapy have, to date,
      increased mortality. There is an urgent need to develop effective strategies to
      improve outcomes for adults with sepsis in sub-Saharan Africa.

PMID- 30223558
TI  - Application of Time-Domain Full Waveform Inversion to Cross-Hole Radar Data
      Measured at Xiuyan Jade Mine, China.
AB  - Xiuyan Jade, produced in Xiuyan County, Liaoning Province, China is one of the
      four famous jade in China. King Jade, which is deemed the largest jade body of
      the world, was broken out from a hill. The local government planned to build a
      tourism site based on the jade culture there. The purpose of the investigation
      was to evaluate the stability of subsurface foundation, and the possible
      positions of mined-out zones to prevent the further rolling of the jade body.
      Cross-hole radar tomography is the key technique in the investigation.
      Conventional travel time and attenuation tomography based on ray tracing theory
      cannot provide high-resolution images because only a fraction of the measured
      information is used in the inversion. Full-waveform inversion (FWI) can provide
      high-resolution permittivity and conductivity images because it utilizes all the
      information provided by the radar signals. We deduce the gradient expression of
      the time-domain FWI with respect to the permittivity and conductivity using a
      method that is different from that of the previous work and realize the FWI
      algorithm that can simultaneously update the permittivity and conductivity by
      using the conjugate gradient method. Inverted results from synthetic data show
      that time-domain FWI can significantly improve the resolution compared with the
      ray-based tomogram methods. FWI can distinguish targets that are as small as one
      half to one-third wavelength and the inverted physical values are closer to the
      real ones than those provided by the ray tracing method. We use the FWI algorithm
      to the field data measured at Xiuyan jade mine. Both the inverted permittivity
      and conductivity can comparably delineate four mined-out zones, which exhibit low
      permittivity and low-conductivity characteristics. Furthermore, the locations of
      the interpreted mined-out zones are in good agreement with the existing mining
      channels recorded by geological data.

PMID- 30223559
TI  - Electrospinning of Ethylene Vinyl Acetate/Poly(Lactic Acid) Blends on a Water
      Surface.
AB  - The electrospinning of an ethylene vinyl acetate (EVA) copolymer with a vinyl
      acetate content of 28 wt.% is limited due to the solubility of the copolymer in
      standard laboratory conditions. Poly(lactic acid) (PLA) is a biodegradable
      polymer that can be electrospun easily. However, PLA has limited applicability
      because it is brittle. Blends of these polymers are of interest in order to
      obtain new types of materials with counterbalanced properties originating from
      both polymeric compounds. The fibers were electrospun on a water surface from a
      solution mixture containing various weight ratios of both polymers using a
      dichloromethane and acetone (70:30 v/v) mixture as solvent. The morphologies of
      the prepared non-woven mats were examined by scanning electron microscopy (SEM),
      and the chemical composition was investigated by X-ray photoelectron spectroscopy
      (XPS) and by Fourier Transform Infrared Spectroscopy (FTIR). The fibers' thermal
      properties and stability were examined, and the mechanical properties were
      tested. The results showed that the strength and flexibility of the blend samples
      were enhanced by the presence of PLA.

PMID- 30223557
TI  - Proteomics and Lipidomics in Inflammatory Bowel Disease Research: From
      Mechanistic Insights to Biomarker Identification.
AB  - Inflammatory bowel disease (IBD) represents a group of progressive disorders
      characterized by recurrent chronic inflammation of the gut. Ulcerative colitis
      and Crohn's disease are the major manifestations of IBD. While our understanding
      of IBD has progressed in recent years, its etiology is far from being fully
      understood, resulting in suboptimal treatment options. Complementing other
      biological endpoints, bioanalytical "omics" methods that quantify many
      biomolecules simultaneously have great potential in the dissection of the complex
      pathogenesis of IBD. In this review, we focus on the rapidly evolving proteomics
      and lipidomics technologies and their broad applicability to IBD studies; these
      range from investigations of immune-regulatory mechanisms and biomarker discovery
      to studies dissecting host-microbiome interactions and the role of intestinal
      epithelial cells. Future studies can leverage recent advances, including improved
      analytical methodologies, additional relevant sample types, and integrative multi
      omics analyses. Proteomics and lipidomics could effectively accelerate the
      development of novel targeted treatments and the discovery of complementary
      biomarkers, enabling continuous monitoring of the treatment response of
      individual patients; this may allow further refinement of treatment and,
      ultimately, facilitate a personalized medicine approach to IBD.

PMID- 30223560
TI  - Fast Regulation of Hormone Metabolism Contributes to Salt Tolerance in Rice
      (Oryzasativa spp. Japonica, L.) by Inducing Specific Morpho-Physiological
      Responses.
AB  - Clear evidence has highlighted a role for hormones in the plant stress response,
      including salt stress. Interplay and cross-talk among different hormonal pathways
      are of vital importance in abiotic stress tolerance. A genome-wide
      transcriptional analysis was performed on leaves and roots of three-day salt
      treated and untreated plants of two Italian rice varieties, Baldo and Vialone
      Nano, which differ in salt sensitivity. Genes correlated with hormonal pathways
      were identified and analyzed. The contents of abscisic acid, indoleacetic acid,
      cytokinins, and gibberellins were measured in roots, stems, and leaves of
      seedlings exposed for one and three days to salt stress. From the transcriptomic
      analysis, a huge number of genes emerged as being involved in hormone regulation
      in response to salt stress. The expression profile of genes involved in
      biosynthesis, signaling, response, catabolism, and conjugation of phytohormones
      was analyzed and integrated with the measurements of hormones in roots, stems,
      and leaves of seedlings. Significant changes in the hormone levels, along with
      differences in morphological responses, emerged between the two varieties. These
      results support the faster regulation of hormones metabolism in the tolerant
      variety that allows a prompt growth reprogramming and the setting up of an
      acclimation program, leading to specific morpho-physiological responses and
      growth recovery.

PMID- 30223561
TI  - Acute Phase Protein Levels as An Auxiliary Tool in Diagnosing Viral Diseases in
      Ruminants-A Review.
AB  - We examined acute phase protein (APP) concentrations in viral infections of dairy
      ruminants and assessed the potential role of characteristic patterns of APP
      changes in auxiliary diagnosing viral diseases. All viruses reviewed are common
      causes of farm animal diseases. APPs are among the first agents of immunity, and
      their concentrations could be diagnostically relevant. In the most common
      ruminant viral diseases, elevated serum amyloid A (SAA) and haptoglobin (Hp)
      levels in blood serum have been observed. However, since these proteins are the
      main APPs in many viral infections, it is impossible to use their levels for
      diagnosing particular infections. Decreased Cp and albumin expression could help
      differentiate the bluetongue virus infection from other diseases. Lastly,
      analysis of SAA levels in blood serum and milk could be helpful in diagnosing
      small ruminant lentivirus infection. While promising, APP levels can only be
      considered as an auxiliary tool in diagnosing viral diseases in ruminants.

PMID- 30223562
TI  - In Vitro Study of Multi-Therapeutic Properties of Thymus bovei Benth. Essential
      Oil and Its Main Component for Promoting Their Use in Clinical Practice.
AB  - Thymus bovei Benth. (TB) is an important plant in the traditional medicine of the
      Mediterranean region. This study investigates the health-promoting properties of
      TB essential oil (TB-EO) for its possible use in clinical practice with regards
      to its cytotoxic, anti-herpes simplex virus type 2 (HSV-2), and antihypertensive
      (through inhibition of human angiotensin-converting enzyme; ACE) properties. The
      phytochemical profile of EO (99.9%) was analyzed by Gas Chromatography with Flame
      Ionization Detection (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS).
      In this study, all biological methods were performed at the level of in vitro
      studies. The results showed that TB-EO exerted remarked cytotoxic properties
      against human cervical carcinoma cells, colon cancer cells, and lung
      adenocarcinoma cells with the half-maximal inhibitory concentration (IC50) values
      of 7.22, 9.30, and 8.62 ug/mL, respectively, in comparison with that of standard
      anticancer drug cisplatin with IC50 values of 4.24, 5.21, and 5.43 ug/mL,
      respectively. Fascinatingly, TB-EO showed very weak cytotoxicity on the healthy
      human fetal lung fibroblast cells with an IC50 value of 118.34 ug/mL compared
      with that of cisplatin (IC50 = 10.08 ug/mL). TB-EO, its main component geraniol,
      TB-EO combined with acyclovir (ACV) along with standard ACV, have displayed
      pronounced inhibitory properties against the replication of HSV-2 with the half
      maximal effective concentration (EC50) values of 2.13, 1.92, 0.81 and 1.94 ug/mL,
      respectively, with corresponding selectivity indices (SI) 98.59, 109.38, 259.26
      and 108.25, respectively. TB-EO and geraniol at a concentration of 15 ug/mL
      showed prominent inhibitory activities against ACE with % of inhibition 95.4% and
      92.2%, respectively, compared with that of standard inhibitor captopril (99.8%;
      15 ug/mL). Molecular docking studies were performed to unveil the mechanism of
      action of geraniol as well as structural parameters necessary for anti-HSV-2
      activity (through the inhibition of HSV-2 protease) and ACE inhibition. This is
      the first report on the chemical composition of Egyptian TB-EO along with the
      above-mentioned biological activities. Our results may be considered as novel
      findings in the course of a search for new and active anticancer, anti-HSV-2 and
      antihypertensive agents, and expand the medicinal value of this plant and its
      phytochemicals in clinical practice.

PMID- 30223563
TI  - Positive Effects of Tomato Paste on Vascular Function After a Fat Meal in Male
      Healthy Subjects.
AB  - : Tomato consumption has been recently associated with a reduced incidence of
      cardiovascular disease (CVD). The aim of this study was to test whether a seven
      day period of tomato paste puree (tomato paste, TP) supplementation could improve
      some haemodynamic parameters in healthy volunteers before and after a
      standardized fat meal (FM). METHODS AND RESULTS: Nineteen healthy male volunteers
      participated in a randomized, single-blind (operator) crossover study.
      Participants maintained low fiber diets (LFD) during the study periods. They were
      randomized either to a LFD and TP arm (80 g of TP/day) for seven-days, or to a
      control arm (LFD-only) with a two-week washout period. Flow Mediated Dilatation
      and other morpho-functional vascular indices were measured by ultrasound.
      Stiffness Index and Reflection Index were estimated by digital photo
      plethysmography. All these parameters were measured one h before and two and 3.5
      h after the FM. The difference in Stiffness Index was increased in the LFD and TP
      + FM-arm, as compared to the LFD-only + FM arm at both two and 3.5 h points.
      After the FM, in both arms, at two h, we observed a reduction in the Reflection
      Index and an increase in heart rate. Interestingly, only in the LFD and TP + FM
      arm, some haemodynamic changes were detectable at two h; notably, there was an
      increase in brachial artery diameter and a reduction in diastolic blood pressure
      (BP). CONCLUSIONS: TP has no effect on Flow Mediated Dilatation but acutely
      modifies some haemodynamic parameters triggered by FM, suggesting possible
      haemodynamic beneficial effects in people consuming tomatoes.

PMID- 30223564
TI  - Motivational Climate in Youth Football Players.
AB  - (1) Background: In recent decades, the psychology of sport has gained special
      relevance in this field, due to the influence of psychological variables on
      sports performance and the regularity of sports practice. The aim of this
      research is to analyse the motivational climate of footballers. (2) Methods: This
      study uses a descriptive cross-sectional design on a sample of 156 adolescent
      football players, using an ad-hoc questionnaire for the recording of socio
      demographic variables and the PMCSQ-2 questionnaire on motivational climate in
      sport. (3) Results: The results of the present investigation indicate that
      footballers are more oriented towards task than ego, sportsmen who compete in
      Honor Division being the those who are more oriented towards ego and those of
      National Division being more oriented towards task. (4) Conclusions: The main
      conclusion of this research is those who are the motivational climate is related
      to the division in which the players compete.

PMID- 30223565
TI  - Analysis of Contact Traces of Cannabis by In-Tube Solid-Phase Microextraction
      Coupled to Nanoliquid Chromatography.
AB  - Because of its inherent qualities, in-tube solid-phase microextraction (IT-SPME)
      coupled on-line to nanoliquid chromatography (nanoLC) can be a very powerful tool
      to address the new challenges of analytical laboratories such as the analysis of
      traces of complex samples. This is the case of the detection of contact traces of
      drugs, especially cannabis. The main difficulties encountered in the analysis of
      traces of cannabis plants on surfaces are the low amount of sample available
      (typically < 1 mg), the complexity of the matrix, and the low percentages of
      cannabinoic compounds in the samples. In this work, a procedure is described for
      the detection of residues of cannabis on different surfaces based on the
      responses obtained by IT-SPME coupled to nanoLC with UV diode array detection
      (DAD) for the cannabinoids Delta8-tetrahydrocannabinol (THC), cannabidiol (CBD),
      and cannabinol (CBN); the proposed conditions can also be applied for
      quantitative purposes through the measurement of the percentage of THC, the most
      abundant cannabinoid in plants. The method is based on collecting the suspected
      drug samples with cotton swabs, followed by the extraction of the target
      compounds by ultrasound assisted extraction. The extracts are then separated and
      processed by IT-SPME-nanoLC. The proposed approach has been applied to the
      detection of traces of cannabis in different kind of items (plastic bags, office
      paper, aluminum foil, cotton cloths, and hand skin). Sample amounts as low as
      0.08 mg have been collected and analysed for THC. The selectivity and effect of
      the storage conditions on the levels of THC have also been evaluated. The
      percentages of THC in the samples typically ranged from 0.6% to 2.8%, which means
      that amounts of this compound as low as 1-2 ug were adequately detected and
      quantified. For the first time, the reliability of IT-SPME-nanoLC for the
      analysis of complex matrices such as cannabis plant extracts has been
      demonstrated.

PMID- 30223566
TI  - Microstructure and Mechanical Properties of Nano-Carbon Reinforced Titanium
      Matrix/Hydroxyapatite Biocomposites Prepared by Spark Plasma Sintering.
AB  - Nano-carbon reinforced titanium matrix/hydroxyapatite (HA) biocomposites were
      successfully prepared by spark plasma sintering (SPS). The microstructure,
      mechanical properties, biocompatibility, and the relationship between
      microstructure and properties of biocomposites were systematically investigated.
      Results showed there are some new phases in sintered composites, such as beta-Ti,
      TiO3, ZrO2, etc. Moreover, a small amount of Ti17P10, CaTiO3, Ca3(PO4)2 were also
      detected. The reaction that may occur during the preparation process is
      suppressed to some extent, which is because that the addition of second phases
      can prevent the direct contact of titanium with HA and reduce the contact areas.
      Transmission electron microscope (TEM) analysis proved the existence of elemental
      diffusion and chemical reactions in sintered composites. Compared with results of
      composites prepared by hot-pressed sintering before, mechanical properties
      (microhardness, compressive strength, and shear strength) of 0.5-GNFs composites
      prepared by SPS were increased by about 2.8, 4.8, and 4.1 times, respectively.
      The better mechanical properties of 0.5-GNFs composite in nano-carbon reinforced
      composites are mainly due to the lower degree of agglomeration of tubular carbon
      nanotubes (CNTs) compared to lamellar graphene nanoflakes (GNFs). Moreover, the
      strengthening and toughening mechanisms of nano-carbon reinforced titanium
      alloy/HA biocomposite prepared by spark plasma sintering (SPS) mainly included
      second phase strengthening, grain refinement strengthening, solution
      strengthening, graphene extraction, carbon nanotubes bridging, crack tail
      stripping, etc. In addition, in vitro bioactivity test revealed that the addition
      of nano-carbon was beneficial to promote the adhesion and proliferation of cells
      on the surface of titanium alloy/HA composite, because nano-carbon can enhance
      the formation of mineralized necks in the composites after transplantation,
      stimulate biomineralization and promote bone regeneration.

PMID- 30223567
TI  - Fibre Bragg Grating Based Strain Sensors: Review of Technology and Applications.
AB  - Fibre Bragg grating (FBG) strain sensors are not only a very well-established
      research field, but they are also acquiring a bigger market share due to their
      sensitivity and low costs. In this paper we review FBG strain sensors with high
      focus on the underlying physical principles, the interrogation, and the read-out
      techniques. Particular emphasis is given to recent advances in highly-performing,
      single head FBG, a category FBG strain sensors belong to. Different sensing
      schemes are described, including FBG strain sensors based on mode splitting.
      Their operation principle and performance are reported and compared with the
      conventional architectures. In conclusion, some advanced applications and key
      sectors the global fibre-optic strain sensors market are envisaged, as well as
      the main market players acting in this field.

PMID- 30223569
TI  - Laboratory and Field Investigation of the Feasibility of Crumb Rubber Waste
      Application to Improve the Flexibility of Anti-Rutting Performance of Asphalt
      Pavement.
AB  - Resistance of asphalt mix to low-temperature cracking and rutting at high
      temperature is very important to ensure the service performance of asphalt
      pavement under seasonal changes in temperature and loading. However, it is
      challenging to balance the improvement of such resistance by using additives,
      e.g., anti-rutting agent (ARA). This study focuses on improving the flexibility
      of anti-rutting asphalt mix by incorporating crumb rubber (CR) and ARA. The
      properties of the prepared modified asphalt mix were evaluated in the laboratory
      by performing wheel tracking, three-point bending, indirect tensile, and uniaxial
      compression tests. The experimental results showed that the dynamic stability of
      modified asphalt mix was significantly increased due to the addition of ARA and
      further improved by incorporating CR. The maximum bending strain at -10  degrees
      C was increased due to the contribution of CR. The results of indirect tensile
      strength and resilient modulus further indicated that the CR-modified anti
      rutting mixture was more flexible. Moreover, the field observation and evaluation
      indicated that the CR-modified anti-rutting asphalt pavement met the standard
      requirements, better than normal asphalt mixture in many parameters. A conclusion
      can be made that incorporating CR in asphalt mixture prepared with ARA can
      improve pavement performance at both high and low in-service temperatures.

PMID- 30223568
TI  - The Pathways of the iRFP713 Unfolding Induced by Different Denaturants.
AB  - Near-infrared fluorescent proteins (NIR FPs) based on the complexes of bacterial
      phytochromes with their natural biliverdin chromophore are widely used as
      genetically encoded optical probes for visualization of cellular processes and
      deep-tissue imaging of cells and organs in living animals. In this work, we show
      that the steady-state and kinetic dependencies of the various spectral
      characteristics of iRFP713, developed from the bacterial phytochrome RpBphP2 and
      recorded at protein unfolding induced by guanidine hydrochloride (GdnHCl),
      guanidine thiocyanate (GTC), and urea, differ substantially. A study of the
      unfolding of three single-tryptophan mutant forms of iRFP713 expectedly revealed
      that protein unfolding begins with the dissociation of the native dimer, while
      the monomers remain compact. A further increase in the denaturant concentration
      leads to the formation of an intermediate state of iRFP713 having hydrophobic
      areas exposed on the protein surface (I). The total surface charge of iRFP713 (pI
      5.86) changes from negative to positive with an increase in the concentration of
      GdnHCl and GTC because the negative charge of glutamic and aspartic acids is
      neutralized by forming salt bridges between the carboxyl groups and GdnH+ ions
      and because the guanidinium cations bind to amide groups of glutamines and
      asparagines. The coincidence of both the concentration of the denaturants at
      which the intermediate state of iRFP713 accumulates and the concentration of
      GdnH+ ions at which the neutralization of the surface charge of the protein in
      this state is ensured results in strong protein aggregation. This is evidently
      realized by iRFP713 unfolding by GTC. At the unfolding of the protein by GdnHCl,
      an intermediate state is populated at higher denaturant concentrations and a
      strong aggregation is not observed. As expected, protein aggregates are not
      formed in the presence of the urea. The aggregation of the protein upon
      neutralization of the charge on the macromolecule surface is the main indicator
      of the intermediate state of protein. The unfolded state of iRFP713, whose
      formation is accompanied by a significant decrease in the parameter A, was found
      to have a different residual structure in the denaturants used.

PMID- 30223570
TI  - Biomarkers for Predicting Clinical Outcomes of Chemoradiation-Based Bladder
      Preservation Therapy for Muscle-Invasive Bladder Cancer.
AB  - Chemoradiation-based bladder preservation therapy (BPT) is currently a curative
      option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at
      favorable risk or an alternative to radical cystectomy (RC) for those who are
      unfit for RC. In BPT, only patients who achieve complete response (CR) after
      chemoradiation have a favorable prognosis and quality of life with a preserved
      functional bladder. Thus, predicting CR and favorable prognosis is important for
      optimal patient selection for BPT. We reviewed biomarkers for predicting the
      clinical outcomes of chemoradiation-based BPT. The biomarkers studied were
      categorized into those related to apoptosis, cell proliferation, receptor
      tyrosine kinases, DNA damage response genes, hypoxia, molecular subtype, and
      others. Among these biomarkers, the Ki-67 labeling index (Ki-67 LI) and meiotic
      recombination 11 may be used for selecting BPT or RC. Ki-67 LI and erythroblastic
      leukemia viral oncogene homolog 2 (erbB2) may be used for predicting both the
      chemoradiation response and the prognosis of patients on BPT. Concurrent use of
      trastuzumab and a combination of carbogen and nicotinamide can overcome
      chemoradiation resistance conferred by erbB2 overexpression and tumor hypoxia.
      Further studies are needed to confirm the practical utility of these biomarkers
      for progress on biomarker-directed personalized management of MIBC patients.

PMID- 30223571
TI  - Comparison of the Biological and Chemical Synthesis of Schwertmannite at a
      Consistent Fe2+ Oxidation Efficiency and the Effect of Extracellular Polymeric
      Substances of Acidithiobacillus ferrooxidans on Biomineralization.
AB  - Schwertmannite is an environmental mineral material that can promote the natural
      passivation of heavy metal elements, thereby reducing environmental pollution
      from toxic elements. However, the fundamental reason for the difference between
      the chemically (H2O2-FeSO4) and biologically (Acidithiobacillus ferrooxidans
      FeSO4) synthesized schwertmannite is still unclear. In this study, X-ray
      diffraction, scanning electron microscopy, the Brunauer-Emmett-Teller method, and
      X-ray fluorescence spectrometry were used to compare the structure, specific
      surface area, and elemental composition of schwertmannite synthesized by
      biological and chemical methods. The removal capacity of As(III) by the two kinds
      of schwertmannite and the effects of extracellular polymeric substances (EPS) on
      biogenetic schwertmannite were also investigated. At a consistent Fe2+ oxidation
      efficiency, the chemical method synthesized more schwertmannite than the
      biological method over a 60-h period. The biosynthesized schwertmannite had a
      "chestnut shell" shape, with a larger particle size and specific surface than the
      chemically synthesized schwertmannite, which was relatively smooth. The saturated
      adsorption capacities of the biologically and chemically synthesized
      schwertmannite were 117.0 and 87.0 mg.g-1, respectively. After exfoliation of the
      EPS from A. ferrooxidans, the biosynthesized schwertmannite displayed a "wool
      ball" shape, with rough particle surfaces, many microporous structures, and a
      larger specific surface area. The schwertmannite yield also increased by about
      45% compared with that before exfoliation, suggesting that the secretion of EPS
      by A. ferrooxidans can inhibit the formation of schwertmannite.

PMID- 30223573
TI  - Loading Range for the Development of Peak Power in the Close-Grip Bench Press
      versus the Traditional Bench Press.
AB  - The close-grip bench press (CGBP) is a variation of the traditional bench press
      (TBP) that uses a narrower grip (~95% biacromial distance) and has application
      for athletes performing explosive arm actions where the hands are positioned
      close to the torso. Limited research has investigated CGBP peak power. Twenty-six
      strength-trained individuals completed a one-repetition maximum TBP and CGBP.
      During two other sessions, subjects completed two repetitions as explosively as
      possible with loads from 20% to 90% for each exercise, with peak power measured
      by a linear position transducer. A factorial ANOVA calculated between- and within
      exercise differences in peak power. Partial correlations controlling for sex
      determined relationships between absolute and relative strength and peak power
      load. Peak power for the TBP occurred at 50% 1RM, and 30% 1RM for the CGBP. There
      were no significant (p = 0.680) differences between peak power at each load when
      comparing the TBP and CGBP. For the within-exercise analysis, there were
      generally no significant differences in TBP and CGBP peak power for the 20-50%
      1RM loads. There were no significant relationships between strength and peak
      power load (p = 0.100-0.587). A peak power loading range of 20-50% 1RM for the
      TBP and CGBP is suggested for strength-trained individuals.

PMID- 30223572
TI  - The Sensitivity, Specificity and Accuracy of Warning Signs in Predicting Severe
      Dengue, the Severe Dengue Prevalence and Its Associated Factors.
AB  - Objectives: To study Malaysian dengue clinical practice guideline (CPG) warning
      signs (WS) in predicting severe dengue (SD) and its associated factors among
      confirmed cases presented to a teaching hospital in north-eastern Malaysia in
      2014. Methods: A cross-sectional study was performed in February 2015 using
      secondary data acquired from the hospital records. There were 2607 confirmed
      dengue cases presented to Hospital Universiti Sains Malaysia (HUSM) in 2014.
      Seven hundred patients were selected after proportionate stratified random
      sampling conducted according to the number of cases in 12 different months in
      2014. Data were collected and analysed using SPSS version 22.0. Results: Severe
      dengue outcomes represented 4.9% of cases. The prevalence of any of WS in SD was
      91.2%. The most common WSs prior to SD were persistent vomiting (55.9%), and
      abdominal pain/tenderness (52.9%). The most sensitive warning sign in detecting
      SD was abdominal pain (59%). Specificity of individual WS were generally good,
      especially of clinical fluid accumulation (99%), hepatomegaly (98%) and mucosal
      bleeding (93%). Factors associated with SD were persistent vomiting (Adjusted
      odds ratio (aOR)): 2.41), mucosal bleeding (aOR: 4.73) and haematocrit rise with
      rapid platelet drop (aOR: 2.74). Conclusion: A focus on sensitivity, specificity,
      predictive values and association of a number of particular WS should be
      emphasized in order to better predict severe dengue outcomes.

PMID- 30223574
TI  - Wireless Channel Propagation Characteristics and Modeling Research in Rice Field
      Sensor Networks.
AB  - Wireless channel propagation characteristics and models are important to ensure
      the communication quality of wireless sensor networks in agriculture. Wireless
      channel attenuation experiments were carried out at different node antenna
      heights (0.8 m, 1.2 m, 1.6 m, and 2.0 m) in the tillering, jointing, and grain
      filling stages of rice fields. We studied the path loss variation trends at
      different transmission distances and analyzed the differences between estimated
      values and measured values of path loss in a free space model and a two-ray
      model. Regression analysis of measured path loss values was used to establish a
      one-slope log-distance model and propose a modified two-slope log-distance model.
      The attenuation speed in wireless channel propagation in rice fields intensified
      with rice developmental stage and the transmission range had monotone increases
      with changes in antenna height. The relative error (RE) of estimation in the free
      space model and the two-ray model under four heights ranged from 6.48-15.49% and
      2.09-13.51%, respectively, and these two models were inadequate for estimating
      wireless channel path loss in rice fields. The ranges of estimated RE for the one
      slope and modified two-slope log-distance models during the three rice
      developmental stages were 2.40-2.25% and 1.89-1.31%, respectively. The one-slope
      and modified two-slope log-distance model had better applicability for modeling
      of wireless channels in rice fields. The estimated RE values for the modified two
      slope log-distance model were all less than 2%, which improved the performance of
      the one-slope log-distance model. This validates that the modified two-slope log
      distance model had better applicability in a rice field environment than the
      other models. These data provide a basis for modeling of sensor network channels
      and construction of wireless sensor networks in rice fields. Our results will aid
      in the design of effective rice field WSNs and increase the transmission quality
      in rice field sensor networks.

PMID- 30223575
TI  - Microwave (MW), Ultrasound (US) and Combined Synergic MW-US Strategies for Rapid
      Functionalization of Pharmaceutical Use Phenols.
AB  - Increasingly stringent regulations aimed at protection of the natural environment
      have stimulated the search for new synthetic methodologies in organic and
      medicinal chemistry having no or minimum harmful effect. An interesting approach
      is the use of alternative activation factors, microwaves (MW) or ultrasounds (US)
      and also their cross-combination, which has been tested in the fast and efficient
      creation of new structures. At present, an easy and green hybrid strategy ("Lego"
      chemistry) is generally recommended for the design of new substances from
      different chemistry building blocks. Often, selected biologically active
      components with specific chemical reactivities are integrated by a suitably
      designed homo- or heterodifunctional linker that modifies the functionality of
      the starting structure, allowing easy covalent linkage to another molecule. In
      this study, a fast introduction of heterodifunctional halogenoacidic linker to
      selected mono-, di- and triphenolic active substances, allowing their
      functionalization, was investigated. Nucleophilic substitution reaction was
      chosen to produce final ethers with the reactive carboxylic group from phenols.
      The functionalization was performed using various green factors initiating and
      supporting the chemical reactions (MW, US, MW-US). The benefits of the three
      green supporting methods and different conditions of reactions were analyzed and
      compared with the results of the reaction performed by conventional methods.

PMID- 30223577
TI  - Modulation of Insulin Resistance and the Adipocyte-Skeletal Muscle Cell Cross
      Talk by LCn-3PUFA.
AB  - The cross-talk between skeletal muscle and adipose tissue is involved in the
      development of insulin resistance (IR) in skeletal muscle, leading to the
      decrease in the anabolic effect of insulin. We investigated if the long chain
      polyunsaturated n-3 fatty acids (LCn-3PUFA), eicosapentaenoic and
      docosapentaenoic acids (EPA and DPA, respectively) could (1) regulate the
      development of IR in 3T3-L1 adipocytes and C2C12 muscle cells and (2) inhibit IR
      in muscle cells exposed to conditioned media (CM) from insulin-resistant
      adipocytes. Chronic insulin (CI) treatment of adipocytes and palmitic acid (PAL)
      exposure of myotubes were used to induce IR in the presence, or not, of LCn
      3PUFA. EPA (50 uM) and DPA (10 uM) improved PAL-induced IR in myotubes, but had
      only a partial effect in adipocytes. CM from adipocytes exposed to CI induced IR
      in C2C12 myotubes. Although DPA increased the mRNA levels of genes involved in
      fatty acid (FA) beta-oxidation and insulin signaling in adipocytes, it was not
      sufficient to reduce the secretion of inflammatory cytokines and prevent the
      induction of IR in myotubes exposed to adipocyte's CM. Treatment with DPA was
      able to increase the release of adiponectin by adipocytes into CM. In conclusion,
      DPA is able to protect myotubes from PAL-induced IR, but not from IR induced by
      CM from adipocytes.

PMID- 30223576
TI  - Roles for the IKK-Related Kinases TBK1 and IKKepsilon in Cancer.
AB  - While primarily studied for their roles in innate immune response, the IkappaB
      kinase (IKK)-related kinases TANK-binding kinase 1 (TBK1) and IKKepsilon also
      promote the oncogenic phenotype in a variety of cancers. Additionally, several
      substrates of these kinases control proliferation, autophagy, cell survival, and
      cancer immune responses. Here we review the involvement of TBK1 and IKKepsilon in
      controlling different cancers and in regulating responses to cancer
      immunotherapy.

PMID- 30223578
TI  - Gastroprotective Activity of Parastrephia quadrangularis (Meyen), Cabrera from
      the Atacama Desert.
AB  - Forty-three metabolites including several methoxylated flavonoids, tremetones,
      and ent-clerodane diterpenes were accurately identified for the first time in the
      ethanolic extract of P. quadrangularis by means of hyphenated UHPLC-quadrupole
      Orbitrap mass spectrometry, and seven isolated compounds were tested regarding
      gastroprotective activity using the HCl/EtOH-induced lesion model in mice. A new
      tremetone (compound 6) is reported based on spectroscopic evidence. The isolated
      clerodanes and tremetones showed gastroprotective activity in a mouse model,
      evidenced by compound 7 (p-coumaroyloxytremetone), which showed the highest
      gastroprotective activity (76%), which was higher than the control drug
      lansoprazole (72%). Our findings revealed that several constituents of this plant
      have gastroprotective activity, and particularly, p-coumaroyloxytremetone could
      be considered as a lead molecule to explore new gastroprotective agents. This
      plant is a rich source of biologically active tremetones and terpenoids which can
      support the ethnobotanical use of the plant.

PMID- 30223580
TI  - Proton Beam Therapy in Combination with Intra-Arterial Infusion Chemotherapy for
      T4 Squamous Cell Carcinoma of the Maxillary Gingiva.
AB  - This study aimed to evaluate the therapeutic effect and toxicity of proton beam
      therapy in combination with intra-arterial infusion chemotherapy in patients with
      squamous cell carcinoma of the maxillary gingiva. Between December 2010 and March
      2016, 30 patients with T4 squamous cell carcinoma of the maxillary gingiva were
      treated with radiotherapy and retrograde intra-arterial infusion chemotherapy
      using cisplatin (20-40 mg/m2, 4-6 times). Radiotherapy was basically administered
      using boost proton beam therapy for primary tumor and neck lymph node tumors,
      following 36-40 Gy photon radiation therapy delivered to the prophylactic area,
      to a total dose of 70.4-74.8 Gy. The median follow-up was 33 months. The 3-year
      local control and overall survival rates were 69% and 59%, respectively. Major
      grade 3 or higher acute toxicities included mucositis, neutropenia, and
      dermatitis in 12 (40%), 5 (17%), and 3 (10%) patients, respectively. No grade 3
      or higher late toxicities were observed. These results suggested that proton beam
      therapy in combination with intra-arterial infusion chemotherapy was not inferior
      to other treatment protocols and should be considered as a safe and effective
      option in patients with T4 squamous cell carcinoma of the maxillary gingiva.

PMID- 30223581
TI  - Quality Assessment of Pork and Turkey Hams Using FT-IR Spectroscopy,
      Colorimetric, and Image Analysis.
AB  - The implementation of fast and nondestructive methods in meat products and colds
      cuts have become increasingly important to evaluate their quality in relation to
      different factors such as origin, type of processing, freshness, adulteration,
      and authenticity. In this study, Fourier Transform Infrared Spectroscopy (FT-IR),
      colorimetric, and image-analysis methods were implemented to characterize and
      classify ham cold cuts in terms of meat type, processing, and shelf life during
      refrigerated storage. Two types of commercial hams (made from pork and turkey)
      and three types of processing (boiled, smoked, and roasted) were selected. By
      using the most appropriate color parameters, a*, h, and C*, as well as the
      textural features' angular second moment, long-running emphasis, and standard
      deviation of image intensity from the hams' images, high-classification values
      for the different ham samples were achieved. The FT-IR analysis revealed the
      presence of absorbance bands of proteins, triglycerides, fatty acids, and
      carbohydrates with different intensities according to meat type and processing.
      Refrigeration storage caused significant alterations of color parameters and a
      partial degradation of triglycerides and proteins. Moreover, the image-analysis
      findings indicated that storage period caused significant degradation of ham
      images relating to local linearity, and structural and textural continuum.

PMID- 30223582
TI  - Long-Term Access to Sit-Stand Workstations in a Large Office Population: User
      Profiles Reveal Differences in Sitting Time and Perceptions.
AB  - Background: To decrease the detrimental health effects of prolonged sitting, the
      implementation of sit-stand workstations is a commonly used intervention for
      office workers. Most studies on this topic evaluated the effects of newly
      introduced sit-stand workstations. The objective of this study was to determine
      how often and how long the standing option is used and how the use of sit-stand
      workstations is perceived in office workers with long-term access to these
      workstations. Methods: Using an online survey, 1098 office employees responded to
      questions about frequency of usage of the sit-stand workstation, sitting time,
      physical activity, and positive and negative perceptions of the use of the sit
      stand workstations. Results: Based on the frequency of use, three user groups
      were identified: non-users (32.1%), monthly/weekly users (37.5%) and daily users
      (30.4%). Non-users reported to sit more, stand less and have longer bouts of
      sitting, compared to monthly/weekly users, and these differences were even larger
      compared to daily users. A higher proportion of daily users perceived the use of
      the sit-stand workstation as being more healthy and appealing and making them
      more productive and energetic compared to the non-users. A higher proportion of
      the non-users perceived it as being uncomfortable, distracting, and unpractical,
      compared to the other user groups. Conclusions: The differences between the three
      identified user groups with respect to sitting, standing and perceptions of sit
      stand workstations, might be helpful in tailoring future interventions to reduce
      occupational sitting time, to increase the reach, effectiveness and
      sustainability.

PMID- 30223583
TI  - Cystic Fibrosis Mortality in Childhood. Data from European Cystic Fibrosis
      Society Patient Registry.
AB  - Data collected in the European Cystic Fibrosis Society Patient Registry (ECFSPR)
      database were used to investigate whether risk factors for death in childhood and
      adolescents CF patients have different impact in countries of different income.
      In this way, it is possible to recognize where interventions could improve the
      quality of care and survival in these patients. We matched deceased and alive
      patients by age, country, year of follow-up. Multivariable logistic models were
      developed. In the years of this study, the ECFSPR collected information on 24,416
      patients younger than 18 years: 7830 patients were from countries with low/middle
      income and 16,586 from countries with high income; among these the dead are 102
      and 107 (p < 0.001), respectively. The use of oxygen, forced expiratory volume in
      one second (FEV1) below 40% and BMI standard deviation score (SDS) below -2
      represent risk factors for death. However, some patients from countries with high
      income remain alive even if their values of FEV1% and BMI-SDS were low, and some
      deceased patients from countries with high income had high values of FEV1%
      (>60%). Evaluation of mortality in pediatric age may reflect the availability of
      resources for CF diagnosis and treatment in some countries.

PMID- 30223585
TI  - Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides
      Based on the 7-Azabicyclic[2.2.1]heptane Scaffold.
AB  - Non-planar amides are usually transitional structures, that are involved in amide
      bond rotation and inversion of the nitrogen atom, but some ground-minimum non
      planar amides have been reported. Non-planar amides are generally sensitive to
      water or other nucleophiles, so that the amide bond is readily cleaved. In this
      article, we examine the reactivity profile of the base-catalyzed hydrolysis of 7
      azabicyclo[2.2.1]heptane amides, which show pyramidalization of the amide
      nitrogen atom, and we compare the kinetics of the base-catalyzed hydrolysis of
      the benzamides of 7-azabicyclo[2.2.1]heptane and related monocyclic compounds.
      Unexpectedly, non-planar amides based on the 7-azabicyclo[2.2.1]heptane scaffold
      were found to be resistant to base-catalyzed hydrolysis. The calculated Gibbs
      free energies were consistent with this experimental finding. The contribution of
      thermal corrections (entropy term, -TDeltaS?) was large; the entropy term
      (DeltaS?) took a large negative value, indicating significant order in the
      transition structure, which includes solvating water molecules.

PMID- 30223584
TI  - The Use of Liquids Ionic Fluids as Pharmaceutically Active Substances Helpful in
      Combating Nosocomial Infections Induced by Klebsiella Pneumoniae New Delhi
      Strain, Acinetobacter Baumannii and Enterococcus Species.
AB  - This review deals with various microbiological activities of ionic liquids, which
      constitute the first anti-infective defense against multi-drug-resistant bacteria
      with a particular emphasis placed on medicine and pharmacology. The quoted data
      on the biological activity of ionic liquids including their antimicrobial
      properties (depending on the type of a cation or an anion) and are discussed in
      view of possible applications in nosocomial infections. Dedicated attention is
      given to finding infections with the Klebsiella pneumoniae New Delhi strain,
      Acinetobacter baumannii, and Enterococcus species, which are responsible for the
      induction of antibiotic resistance in intensive care units. Diagnosis and
      treatment using current antibiotics is a significant problem in hospital care,
      and the relevant burden on the health systems of the European Union member states
      induces the search for new, effective methods of treatment. Ionic liquids, due to
      their antibacterial effect, can be considered topical and general medications and
      may provide the basis for treatment to eliminate the antibiotic resistance
      phenomenon in the future. At present, the number of infections with resistant
      pathogens in hospitals and outpatient clinics in the European Union is growing.
      In 2015-2017, a significant incidence of respiratory and bloodstream infections
      with bacteria resistant to antibiotics from the 3rd generation group of
      cephalosporins, glycopeptides, and carbapenems were observed. The paper presents
      examples of synthesized bifunctional salts with at least one pharmaceutically
      active ion in obtaining a controlled release, controlled delivery, and biological
      impact on the pathogenic bacteria, viruses and fungi. The ionic liquids obtained
      in the presented way may find applications in the treatment of wounds and
      infections.

PMID- 30223586
TI  - Novel Hydroxy- and Epoxy-cis-Jasmone and Dihydrojasmone Derivatives Affect the
      Foraging Activity of the Peach Potato Aphid Myzus persicae (Sulzer) (Homoptera:
      Aphididae).
AB  - Jasmonates show great potential in sustainable agriculture due to their various
      roles in natural mechanisms of plant defense, and because they are non-toxic, non
      mutagenic, and easily metabolized. The aim of the study was to explore structure
      activity relationships of dihydrojasmone, cis-jasmone, and their derivatives at
      the plant-aphid interface. We focused on the behavioral responses of aphids,
      following the exogenous application of natural jasmonates and their derivatives
      to the host plants. Aphid probing behavior was examined using an electrical
      penetration graph technique (EPG). The chemoenzymatic transformation of cis
      jasmone and the activity of two new derivatives are described. The application of
      cis-jasmone, dihydrojasmone, the hydroxyderivatives, epoxyderivatives, and alkyl
      substituted delta-lactones hindered the foraging activity of Myzus persicae
      (Sulz.) (Hemiptera: Aphididae) during early stages of probing at the level of non
      phloem tissues. The application of saturated bicyclic epoxy-delta-lactone
      enhanced plant acceptance by M. persicae. Jasmonate derivatives containing a
      hydroxy group, especially in correlation with a lactone ring, were more active
      than natural compounds and other derivatives studied. Jasmonates of the present
      study are worth considering as elements of sustainable aphid control as
      components of the "push-pull" strategy.

PMID- 30223587
TI  - A Dairy-Derived Ghrelinergic Hydrolysate Modulates Food Intake In Vivo.
AB  - Recent times have seen an increasing move towards harnessing the health-promoting
      benefits of food and dietary constituents while providing scientific evidence to
      substantiate their claims. In particular, the potential for bioactive protein
      hydrolysates and peptides to enhance health in conjunction with conventional
      pharmaceutical therapy is being investigated. Dairy-derived proteins have been
      shown to contain bioactive peptide sequences with various purported health
      benefits, with effects ranging from the digestive system to cardiovascular
      circulation, the immune system and the central nervous system. Interestingly, the
      ability of dairy proteins to modulate metabolism and appetite has recently been
      reported. The ghrelin receptor (GHSR-1a) is a G-protein coupled receptor which
      plays a key role in the regulation of food intake. Pharmacological manipulation
      of the growth hormone secretagogue receptor-type 1a (GHSR-1a) receptor has
      therefore received a lot of attention as a strategy to combat disorders of
      appetite and body weight, including age-related malnutrition and the progressive
      muscle wasting syndrome known as cachexia. In this study, a milk protein
      derivative is shown to increase GHSR-1a-mediated intracellular calcium signalling
      in a concentration-dependent manner in vitro. Significant increases in calcium
      mobilisation were also observed in a cultured neuronal cell line heterologously
      expressing the GHS-R1a. In addition, both additive and synergistic effects were
      observed following co-exposure of GHSR-1a to both the hydrolysate and ghrelin.
      Subsequent in vivo studies monitored standard chow intake in healthy male and
      female Sprague-Dawley rats after dosing with the casein hydrolysate (CasHyd).
      Furthermore, the provision of gastro-protected oral delivery to the bioactive in
      vivo may aid in the progression of in vitro efficacy to in vivo functionality. In
      summary, this study reports a ghrelin-stimulating bioactive peptide mixture
      (CasHyd) with potent effects in vitro. It also provides novel and valuable
      translational data supporting the potential role of CasHyd as an appetite
      enhancing bioactive. Further mechanistic studies are required in order to confirm
      efficacy as a ghrelinergic bioactive in susceptible population groups.

PMID- 30223588
TI  - Peripheral Network Connectivity Analyses for the Real-Time Tracking of Coupled
      Bodies in Motion.
AB  - Dyadic interactions are ubiquitous in our lives, yet they are highly challenging
      to study. Many subtle aspects of coupled bodily dynamics continuously unfolding
      during such exchanges have not been empirically parameterized. As such, we have
      no formal statistical methods to describe the spontaneously self-emerging
      coordinating synergies within each actor's body and across the dyad. Such
      cohesive motion patterns self-emerge and dissolve largely beneath the awareness
      of the actors and the observers. Consequently, hand coding methods may miss
      latent aspects of the phenomena. The present paper addresses this gap and
      provides new methods to quantify the moment-by-moment evolution of self-emerging
      cohesiveness during highly complex ballet routines. We use weighted directed
      graphs to represent the dyads as dynamically coupled networks unfolding in real
      time, with activities captured by a grid of wearable sensors distributed across
      the dancers' bodies. We introduce new visualization tools, signal
      parameterizations, and a statistical platform that integrates connectivity
      metrics with stochastic analyses to automatically detect coordination patterns
      and self-emerging cohesive coupling as they unfold in real-time. Potential
      applications of these new techniques are discussed in the context of personalized
      medicine, basic research, and the performing arts.

PMID- 30223589
TI  - Chinese Urban Hui Muslims' Access to and Evaluation of Cardiovascular Diseases
      Related Health Information from Different Sources.
AB  - This research aims to identify the sources that urban Hui Muslims access to get
      health information related to cardiovascular diseases (CVD) and how they evaluate
      the information from different sources. This paper focuses on health information
      related to cardiovascular diseases among Hui Muslims. The data was gathered by
      means of an online survey administered on mobile devices. To put the answers
      given by Hui Muslims into perspective and make a comparison between Hui Muslims
      and the Han people, we also gathered information from Han-the dominant group in
      China. The results showed that Chinese Hui Muslims mostly used mediated sources,
      while Han people mainly used interpersonal sources. Both Hui Muslims and Han
      people trusted and preferred health information about cardiovascular diseases
      provided by health organizations, doctors, and healthcare providers. The
      information given by religious leaders was trusted the least, although Hui
      Muslims were significantly more positive about religious authority than the Han
      people. The current results are relevant for Chinese health information promoters
      and can help them diffuse CVD health information more effectively to urban Hui
      Muslims.

PMID- 30223579
TI  - Neurodegenerative Diseases: Regenerative Mechanisms and Novel Therapeutic
      Approaches.
AB  - Regeneration refers to regrowth of tissue in the central nervous system. It
      includes generation of new neurons, glia, myelin, and synapses, as well as the
      regaining of essential functions: sensory, motor, emotional and cognitive
      abilities. Unfortunately, regeneration within the nervous system is very slow
      compared to other body systems. This relative slowness is attributed to increased
      vulnerability to irreversible cellular insults and the loss of function due to
      the very long lifespan of neurons, the stretch of cells and cytoplasm over
      several dozens of inches throughout the body, insufficiency of the tissue-level
      waste removal system, and minimal neural cell proliferation/self-renewal
      capacity. In this context, the current review summarized the most common features
      of major neurodegenerative disorders; their causes and consequences and proposed
      novel therapeutic approaches.

PMID- 30223591
TI  - Intravenous Infusion of Nucleated Peripheral Blood Cells Restores Fertility in
      Mice with Chemotherapy-Induced Premature Ovarian Failure.
AB  - Cancer treatment with specific chemotherapeutic agents has been well documented
      to have an adverse impact on female fertility leading to premature ovarian
      failure (POF). The objective of this study is to investigate if chemotherapeutic
      induced POF can be reversed by the infusion of autologous nucleated peripheral
      blood cells (PBMC). To reach our goal, mice were treated with a single
      intraperitoneal injections of busulfan and cyclophosphamide to induce POF. This
      was followed by transfusion of PBMC. The ovarian morphology and functional
      parameters were monitored by radioimmunoassay, real-time PCR, immunofluorescence
      and immunohistochemistry analysis. Our study showed that chemotherapy (CTX)
      protracted estrous cycle period and repressed E2 production. In addition, CTX
      decreased the expressions of steroidogenesis markers, CYP-17 synthesis, StAR
      (steroidogenic acute regulatory protein), and Connexin-43 protein expression in
      the ovarian follicles. We also observed reduced numbers and sizes of the
      primordial and primary follicles in CTX-treated mice compared to untreated
      controls (p < 0.05). When both CTX and untreated control groups were stimulated
      with gonadotrophin, the control group produced ten times more ova than the CTX
      group. Finally, the treatment of premature ovarian failure induced by CTX with
      autologous PBMC transfusion resulted in over-expression and a statistically
      significant increase in several stem cell markers and restoration of fertility.
      Infusion with PBMC in CTX further decreased the estrous cycle length by 2.5 times
      (p < 0.01). We found that transfusion of autologous PBMC to mice with
      chemotherapy induced POF was very effective at restoring fertility. These results
      are similar to other studies using bone marrow derived mesenchymal stem cells.

PMID- 30223590
TI  - HDAC-Linked "Proliferative" miRNA Expression Pattern in Pancreatic Neuroendocrine
      Tumors.
AB  - : Epigenetic factors are essentially involved in carcinogenesis, tumor promotion,
      and chemoresistance. Two epigenetic key players are miRNAs and histone
      deacetylases (HDACs). As previously shown by own theoretical databank analysis,
      the crosstalk between miRNAs and HDACs is relevant in different human chronic
      diseases and cancerogenic pathways. We aimed to investigate a potential
      connection between the expression of a well-defined subset of "proliferation
      associated" miRNAs and the expression of HDACs as well as clinical parameters in
      pancreatic neuroendocrine tumors (pNETs). MATERIALS AND METHODS: Expression
      levels of miRNA132-3p, miRNA145-5p, miRNA183-5p, miRNA34a-5p, and miRNA449a in 57
      pNETs resected between 1997 and 2015 were measured and linked to the
      immunohistochemical expression pattern of members of the four HDAC classes on
      human tissue microarrays. All pNET cases were clinically and pathologically
      characterized according to published guidelines. Correlation analysis revealed a
      significant association between expression of specific miRNAs and two members of
      the HDAC family (HDAC3 and HDAC4). Additionally, a linkage between miRNA
      expression and clinico-pathological parameters like grading, TNM-staging, and
      hormone activity was found. Moreover, overall and disease-free survival is
      statistically correlated with the expression of the investigated miRNAs. Overall,
      we demonstrated that specific miRNAs could be linked to HDAC expression in pNETs.
      Especially miRNA449a (associated with HDAC3/4) seems to play an important role in
      pNET proliferation and could be a potential prognostic factor for poor survival.
      These first data could help, to improve our knowledge of the complex interactions
      of the epigenetic drivers in pNETs for further therapeutic approaches.

PMID- 30223593
TI  - Moderate Intensity Intermittent Exercise Modality May Prevent Cardiovascular
      Drift.
AB  - Cardiovascular drift (CV-Drift) may occur after the ~10th min of submaximal
      continuous exercising. The purpose of this study was to examine whether CV-Drift
      is prevented by an intermittent exercise modality, instead of a continuous
      exercise. Seven well-trained male cyclists volunteered to take part in the study
      ( V  O2max: 61.7 +/- 6.13 mL.min-1.kg-1). Following familiarization sessions,
      athletes' individual maximal O2 consumption ( V  O2max), maximum stroke volume
      responses (SVmax), and cardiac outputs (Qc) were evaluated by a nitrous-oxide re
      breathing system and its gas analyzer. Then, continuous exercises were performed
      30 min at cyclists' 60% V  O2max, while intermittent exercises consisted of three
      10 min with 1:0.5 workout/recovery ratios at the same intensity. Qc measurements
      were taken at the 5th, 9th, 12nd, 15th, 20th, 25th, and 30th min of continuous
      exercises versus 5th and 10th min of workout phases of intermittent exercise
      modality. Greater than a 5% SV decrement, with accompanying HR, increase, while
      Qc remained stable and was accepted as CV-Drift criterion. It was demonstrated
      that there were greater SV responses throughout intermittent exercises when
      compared to continuous exercises (138.9 +/- 17.9 vs. 144.5 +/- 14.6 mL,
      respectively; p <= 0.05) and less HR responses (140.1 +/- 14.8 vs. 135.2 +/- 11.6
      bpm, respectively; p <= 0.05), while mean Qc responses were similar (19.4 +/- 2.1
      vs. 19.4 +/- 1.5 L, respectively; p > 0.05). Moreover, the mean times spent at
      peak SV scores of exercise sessions were greater during intermittent exercise
      (1.5 vs. 10 min) (p < 0.001). In conclusion, intermittent exercises reduce CV
      Drift risk and increases cardiac adaptation potentials of exercises with less
      physiological stress.

PMID- 30223592
TI  - An Analytical Framework for Integrating the Spatiotemporal Dynamics of
      Environmental Context and Individual Mobility in Exposure Assessment: A Study on
      the Relationship between Food Environment Exposures and Body Weight.
AB  - In past studies, individual environmental exposures were largely measured in a
      static manner. In this study, we develop and implement an analytical framework
      that dynamically represents environmental context (the environmental context
      cube) and effectively integrates individual daily movement (individual space-time
      tunnel) for accurately deriving individual environmental exposures (the
      environmental context exposure index). The framework is applied to examine the
      relationship between food environment exposures and the overweight status of 46
      participants using data collected with global positioning systems (GPS) in
      Columbus, Ohio, and binary logistic regression models. The results indicate that
      the proposed framework generates more reliable measurements of individual food
      environment exposures when compared to other widely used methods. Taking into
      account the complex spatial and temporal dynamics of individual environmental
      exposures, the proposed framework also helps to mitigate the uncertain geographic
      context problem (UGCoP). It can be used in other environmental health studies
      concerning environmental influences on a wide range of health behaviors and
      outcomes.

PMID- 30223595
TI  - Removal Properties of Anionic Dye Eosin by Cetyltrimethylammonium Organo-Clays:
      The Effect of Counter-Ions and Regeneration Studies.
AB  - The organo-clays (OCs) were prepared by a cation exchange reaction between
      surfactant (cetyltrimethylammonium, C16TMA) from different counterions (Bromide,
      Chloride, and Hydroxide). The effect of the counterions was investigated on the
      physico-chemical properties of the prepared organo-clays. The highest uptake of
      organic cations (1.60 mmol/g) was achieved using cetyl trimethylammonium bromide
      solution and the lowest value (0.93 mmol/g) was obtained after modification with
      cetyl trimethylammonium hydroxide solution starting from the same initial ratio
      of mmol/g of clay greater than 2.40. The arrangement of C16TMA cations within the
      interlayer space was assumed to be perpendicular with a tilt angle of 32 degrees 
      to the plane of clay sheets instead of being parallel to the clay surface using
      C16TMAOH solution at the same ratio. Different techniques were used to
      characterize these materials. The thermal stability of these organ-clays was
      investigated using an in-situ X-ray diffraction (XRD) technique. The
      decomposition of the surfactant moiety occurred at temperatures higher than 215 
      degrees C and was accompanied with a shrinkage of the basal spacing value to 1.42
      nm. These materials were applied in the removal of an acid dye "eosin." The
      removed amount of eosin depended on the initial concentrations and the content of
      surfactants in the organo-clays. The removal of eosin was found to be an
      endothermic process. The maximum amount of 90 mg/g was achieved. The preheated
      treatment temperature of two selected OCs did affect the removal properties of
      eosin. A progressive reduction was observed at temperatures higher than 200 
      degrees C. The regeneration of spent OCs was studied and acceptable removal
      efficiency was maintained after 4 to 6 cycles depending on the used initial
      concentrations.

PMID- 30223594
TI  - Combined Therapy with SS31 and Mitochondria Mitigates Myocardial Ischemia
      Reperfusion Injury in Rats.
AB  - Myocardial ischemia-reperfusion (IR) injury contributes to adverse cardiac
      outcomes after myocardial ischemia, cardiac surgery, or circulatory arrest. In
      this study, we evaluated the ability of combined SS31-mitochondria (Mito) therapy
      to protect heart cells from myocardial IR injury. Adult male SD rats (n = 8/each
      group) were randomized: group 1 (sham-operated control), group 2 (IR, 30-min
      ischemia/72 h reperfusion), group 3 (IR-SS31 (2 mg intra-peritoneal injection at
      30 min/24 h/48 h after IR)), group 4 (IR-mitochondria (2 mg/derived from donor
      liver/intra-venous administration/30 min after IR procedure)), and group 5 (IR
      SS31-mitochondria). In H9C2 cells, SS31 suppressed menadione-induced oxidative
      stress markers (NOX-1, NOX-2, oxidized protein) while it increased SIRT1/SIRT3
      expression and ATP levels. In adult male rats 72 h after IR, left ventricular
      ejection fraction (LVEF) was highest in sham-operated control animals and lowest
      in the IR group. LVEF was also higher in IR rats treated with SS31-Mito than
      untreated IR rats or those treated with Mito or SS31 alone. Areas of
      fibrosis/collagen-deposition showed the opposite pattern. Likewise, levels of
      oxidative-stress markers (NOX-1, NOX-2, oxidized protein), inflammatory markers
      (MMP-9, CD11, IL-1beta, TNF-alpha), apoptotic markers (mitochondrial-Bax, cleaved
      caspase-3, PARP), fibrosis markers (p-Smad3, TGF-beta), DNA-damage (gamma-H2AX),
      sarcomere-length, and pressure/volume overload markers (BNP, beta-MHC) all showed
      a pattern opposite that of LVEF. Conversely, anti-apoptotic (BMP-2, Smad1/5) and
      energy integrity (PGC-1alpha/mitochondrial cytochrome-C) markers exhibited a
      pattern identical to that of LVEF. This study demonstrates that the combined SS31
      Mito therapy is superior to either therapy alone for protecting myocardium from
      IR injury and indicates that the responsible mechanisms involved increased
      SIRT1/SIRT3 expression, which suppresses inflammation and oxidative stress and
      protects mitochondrial integrity.

PMID- 30223596
TI  - Entropy Correlation and Its Impacts on Data Aggregation in a Wireless Sensor
      Network.
AB  - A correlation characteristic has significant potential advantages for the
      development of efficient communication protocols in wireless sensor networks
      (WSNs). To exploit the correlation in WSNs, the correlation model is required.
      However, most of the present correlation models are linear and distance
      dependent. This paper proposes a general distance-independent entropy correlation
      model based on the relation between joint entropy and the number of members in a
      group. This relation is estimated using entropy of individual members and entropy
      correlation coefficients of member pairs. The proposed model is then applied to
      evaluate two data aggregation schemes in WSNs including data compression and
      representative schemes. In the data compression scheme, some main routing
      strategies are compared and evaluated to find the most appropriate strategy. In
      the representative scheme, with the desired distortion requirement, a method to
      calculate the number of representative nodes and the selection of these nodes are
      proposed. The practical validations showed the effectiveness of the proposed
      correlation model and data reduction schemes.

PMID- 30223598
TI  - A Scene Recognition and Semantic Analysis Approach to Unhealthy Sitting Posture
      Detection during Screen-Reading.
AB  - Behavior analysis through posture recognition is an essential research in robotic
      systems. Sitting with unhealthy sitting posture for a long time seriously harms
      human health and may even lead to lumbar disease, cervical disease and myopia.
      Automatic vision-based detection of unhealthy sitting posture, as an example of
      posture detection in robotic systems, has become a hot research topic. However,
      the existing methods only focus on extracting features of human themselves and
      lack understanding relevancies among objects in the scene, and henceforth fail to
      recognize some types of unhealthy sitting postures in complicated environments.
      To alleviate these problems, a scene recognition and semantic analysis approach
      to unhealthy sitting posture detection in screen-reading is proposed in this
      paper. The key skeletal points of human body are detected and tracked with a
      Microsoft Kinect sensor. Meanwhile, a deep learning method, Faster R-CNN, is used
      in the scene recognition of our method to accurately detect objects and extract
      relevant features. Then our method performs semantic analysis through Gaussian
      Mixture behavioral clustering for scene understanding. The relevant features in
      the scene and the skeletal features extracted from human are fused into the
      semantic features to discriminate various types of sitting postures. Experimental
      results demonstrated that our method accurately and effectively detected various
      types of unhealthy sitting postures in screen-reading and avoided error detection
      in complicated environments. Compared with the existing methods, our proposed
      method detected more types of unhealthy sitting postures including those that the
      existing methods could not detect. Our method can be potentially applied and
      integrated as a medical assistance in robotic systems of health care and
      treatment.

PMID- 30223597
TI  - Analysis of Biomolecules Based on the Surface Enhanced Raman Spectroscopy.
AB  - Analyzing biomolecules is essential for disease diagnostics, food safety
      inspection, environmental monitoring and pharmaceutical development. Surface
      enhanced Raman spectroscopy (SERS) is a powerful tool for detecting biomolecules
      due to its high sensitivity, rapidness and specificity in identifying molecular
      structures. This review focuses on the SERS analysis of biomolecules originated
      from humans, animals, plants and microorganisms, combined with nanomaterials as
      SERS substrates and nanotags. Recent advances in SERS detection of target
      molecules were summarized with different detection strategies including label
      free and label-mediated types. This comprehensive and critical summary of SERS
      analysis of biomolecules might help researchers from different scientific
      backgrounds spark new ideas and proposals.

PMID- 30223599
TI  - Design of a Novel Six-Axis Wrist Force Sensor.
AB  - A novel elastic body design idea of six-axis wrist force sensor with a floating
      beam was raised based on the analysis of the robot six-axis wrist force sensor
      with a floating beam. The design ideas improve the sensor's dynamic performance
      significantly, while not reducing its sensitivity. First, the design ideas were
      described in detail, which were analyzed by mechanical modeling and were verified
      by finite element analysis. Second, the static simulation analysis of the novel
      elastomer of sensor was carried out. According to the strain distribution
      performance, the position of the strain gauges pasted and the connection mode of
      the full-bridge circuits were decided, which can achieve theoretical decoupling.
      Finally, the comparison between the static and dynamic performance of the novel
      sensor and the original sensor with floating beams was done. The results show
      that the static and dynamic performance of the novel six-axis wrist sensor are
      all better than the original sensor.

PMID- 30223601
TI  - Development and Validation of the Questionnaire of Academic Stress in Secondary
      Education: Structure, Reliability and Nomological Validity.
AB  - This study presents the validation process of the Questionnaire on Academic
      Stress in Secondary Education (QASSE) designed to assess the wide variety of
      school sources and situations related to academic stress in adolescence, and
      their relationship with students' physical and psychological well-being. The
      participants were 860 Spanish high school students (52.9% girls) with an average
      age of 14.62 years (SD = 1.8). Through a cross-validation process, results
      supported the QASSE multifactorial structure with four first-order factors
      academic overload, interaction with classmates, family pressure, and future
      oriented perspective-and a second-order factor of academic stress, showing a
      significant and intense relationship with adolescents' psychological and physical
      well-being. Results also highlight the effects of the gender and educational
      level interaction on the students' stress, with girls showing higher levels of
      stress in the transition courses between educational phases (sophomore and junior
      years). The QASSE demonstrates good validity and reliability, showing potential
      for both research and educational application. The results show the high impact
      of the QASSE dimensions on psychological and physical well-being in adolescence,
      highlighting its special usefulness for designing and adjusting educational
      prevention and intervention actions in this area to the students' specific
      characteristics and needs.

PMID- 30223600
TI  - Deep Airway Inflammation and Respiratory Disorders in Nanocomposite Workers.
AB  - Thousands of researchers and workers worldwide are employed in nanocomposites
      manufacturing, yet little is known about their respiratory health. Aerosol
      exposures were characterized using real time and integrated instruments. Aerosol
      mass concentration ranged from 0.120 mg/m3 to 1.840 mg/m3 during nanocomposite
      machining processes; median particle number concentration ranged from 4.8 * 104
      to 5.4 * 105 particles/cm3. The proportion of nanoparticles varied by process
      from 40 to 95%. Twenty employees, working in nanocomposite materials research
      were examined pre-shift and post-shift using spirometry and fractional exhaled
      nitric oxide (FeNO) in parallel with 21 controls. Pro-inflammatory leukotrienes
      (LT) type B4, C4, D4, and E4; tumor necrosis factor (TNF); interleukins; and anti
      inflammatory lipoxins (LXA4 and LXB4) were analyzed in their exhaled breath
      condensate (EBC). Chronic bronchitis was present in 20% of researchers, but not
      in controls. A significant decrease in forced expiratory volume in 1 s (FEV1) and
      FEV1/forced vital capacity (FVC) was found in researchers post-shift (p ? 0.05).
      Post-shift EBC samples were higher for TNF (p ? 0.001), LTB4 (p ? 0.001), and
      LTE4 (p ? 0.01) compared with controls. Nanocomposites production was associated
      with LTB4 (p ? 0.001), LTE4 (p ? 0.05), and TNF (p ? 0.001), in addition to pre
      shift LTD4 and LXB4 (both p ? 0.05). Spirometry documented minor, but
      significant, post-shift lung impairment. TNF and LTB4 were the most robust
      markers of biological effects. Proper ventilation and respiratory protection are
      required during nanocomposites processing.

PMID- 30223604
TI  - Helicopter Test of a Strapdown Airborne Gravimetry System.
AB  - Airborne gravimetry from a helicopter has been a feasible tool since the 1990s,
      with gravimeters mounted on a gyro-stabilised platform. In contrast to fixed-wing
      aircrafts, the helicopter allows for a higher spatial resolution, since it can
      move slower and closer to the ground. In August 2016, a strapdown gravimetry test
      was carried out over the Jakobshavn Glacier in Greenland. To our knowledge, this
      was the first time that a strapdown system was used in a helicopter. The
      strapdown configuration is appealing because it is easily installed and requires
      no operation during flight. While providing additional information over the
      thickest part of the glacier, the survey was designed to assess repeatability
      both within the survey and with respect to profiles flown previously using a gyro
      stabilised gravimeter. The system's ability to fly at an altitude following the
      terrain, i.e., draped flying, was also tested. The accuracy of the gravity
      profiles was estimated to 2 mGal and a method for inferring the spatial
      resolution was investigated, yielding a half-wavelength spatial resolution of 4.5
      km at normal cruise speed.

PMID- 30223602
TI  - Electricity Consumption Estimation of the Polymer Material Injection-Molding
      Manufacturing Process: Empirical Model and Application.
AB  - Polymer injection-molding is one of the most used manufacturing processes for the
      production of plastic products. Its electricity consumption highly influences its
      cost as well as its environmental impact. Reducing these factors is one of the
      challenges that material science and production engineering face today. However,
      there is currently a lack of data regarding electricity consumption values for
      injection-molding, which leads to significant errors due to the inherent high
      variability of injection-molding and its configurations. In this paper, an
      empirical model is proposed to better estimate the electricity consumption and
      the environmental impact of the injection-molding process. This empirical model
      was created after measuring the electricity consumption of a wide range of parts.
      It provides a method to estimate both electricity consumption and environmental
      impact, taking into account characteristics of both the molded parts and the
      molding machine. A case study of an induction cooktop housing is presented,
      showing adequate accuracy of the empirical model and the importance of proper
      machine selection to reduce cost, electricity consumption, and environmental
      impact.

PMID- 30223603
TI  - Adverse Hemodynamic Conditions Associated with Mechanical Heart Valve Leaflet
      Immobility.
AB  - Artificial heart valves may dysfunction, leading to thrombus and/or pannus
      formations. Computational fluid dynamics is a promising tool for improved
      understanding of heart valve hemodynamics that quantify detailed flow velocities
      and turbulent stresses to complement Doppler measurements. This combined
      information can assist in choosing optimal prosthesis for individual patients,
      aiding in the development of improved valve designs, and illuminating subtle
      changes to help guide more timely early intervention of valve dysfunction. In
      this computational study, flow characteristics around a bileaflet mechanical
      heart valve were investigated. The study focused on the hemodynamic effects of
      leaflet immobility, specifically, where one leaflet does not fully open. Results
      showed that leaflet immobility increased the principal turbulent stresses (up to
      400%), and increased forces and moments on both leaflets (up to 600% and 4000%,
      respectively). These unfavorable conditions elevate the risk of blood cell damage
      and platelet activation, which are known to cascade to more severe leaflet
      dysfunction. Leaflet immobility appeared to cause maximal velocity within the
      lateral orifices. This points to the possible importance of measuring maximal
      velocity at the lateral orifices by Doppler ultrasound (in addition to the
      central orifice, which is current practice) to determine accurate pressure
      gradients as markers of valve dysfunction.

PMID- 30223605
TI  - Combination of Sensory, Chromatographic, and Chemometrics Analysis of Volatile
      Organic Compounds for the Discrimination of Authentic and Unauthentic Harumanis
      Mangoes.
AB  - This study analyzed the volatile organic compounds (VOCs) of three mango
      varieties (Harumanis, Tong Dam and Susu) for the discrimination of authentic
      Harumanis from other mangoes. The VOCs of these mangoes were extracted and
      analysed nondestructively using Head Space-Solid Phase Micro Extraction (HS-SPME)
      coupled to Gas Chromatography-Mass Spectrometry (GC-MS). Prior to the analytical
      method, two simple sensory analyses were carried out to assess the ability of the
      consumers to differentiate between the Harumanis and Tong Dam mangoes as well as
      their preferences towards these mangoes. On the other hand, chemometrics
      techniques, such as principal components analysis (PCA), hierarchical clustering
      analysis (HCA), and discriminant analysis (DA), were used to visualise grouping
      tendencies of the volatile compounds detected. These techniques were successful
      in identifying the grouping tendencies of the mango samples according to the
      presence of their respective volatile compounds, thus enabling the identification
      of the groups of substances responsible for the discrimination between the
      authentic and unauthentic Harumanis mangoes. In addition, three ocimene
      compounds, namely beta-ocimene, trans beta-ocimene, and allo-ocimene, can be
      considered as chemical markers of the Harumanis mango, as these compounds exist
      in all Harumanis mango, regardless the different sources of the mangoes obtained.

PMID- 30223606
TI  - Mesenchymal Stem Cells as New Therapeutic Approach for Diabetes and Pancreatic
      Disorders.
AB  - Diabetes is a worldwide disease which actually includes different disorders
      related to glucose metabolism. According to different epidemiological studies,
      patients affected by diabetes present a higher risk to develop both acute and
      chronic pancreatitis, clinical situations which, in turn, increase the risk to
      develop pancreatic cancer. Current therapies are able to adjust insulin levels
      according to blood glucose peak, but they only partly reach the goal to abrogate
      the consequent inflammatory milieu responsible for diabetes-related diseases. In
      recent years, many studies have investigated the possible use of adult
      mesenchymal stem cells (MSCs) as alternative therapeutic treatment for diabetes,
      with promising results due to the manifold properties of these cells. In this
      review we will critically analyze the many different uses of MSCs for both
      diabetes treatment and for the reduction of diabetes-related disease development,
      focusing on their putative molecular mechanisms.

PMID- 30223607
TI  - Investigation on the Thermal Behavior, Mechanical Properties and Reaction
      Characteristics of Al-PTFE Composites Enhanced by Ni Particle.
AB  - Al-PTFE (aluminum-polytetrafluoroethene) is regarded as one of the most promising
      reactive materials (RMs). In this work, Ni (Nickel) was added to Al-PTFE
      composites for the purpose of improving the energy density and damage effect. To
      investigate the thermal behavior, mechanical properties and reaction
      characteristics of the Al-Ni-PTFE composites, an Al-PTFE mixture and an Al-Ni
      mixture were prepared by ultrasonic mixing. Six types of Al-Ni-PTFE specimens
      with different component mass ratios were prepared by molding sintering.
      Simultaneous thermal analysis experiments were carried out to characterize the
      thermal behavior of the Al-PTFE mixture and the Al-Ni mixture. Quasi-static
      compression tests were performed to analyze the mechanical properties and
      reaction characteristics of the Al-Ni-PTFE specimens. The results indicate that
      the reaction onset temperature of Al-Ni (582.7  degrees C) was similar to that of
      Al-PTFE (587.6  degrees C) and that the reaction heat of Al-Ni (991.9 J/g) was
      12.5 times higher than that of Al-PTFE (79.6 J/g). With the increase of Ni
      content, the material changed from ductile to brittle and the strain hardening
      modulus and compressive strength rose first and then subsequently decreased,
      reaching a maximum of 51.35 MPa and 111.41 MPa respectively when the volume
      fraction of Ni was 10%. An exothermic reaction occurred for the specimens with a
      Ni volume fraction no more than 10% under quasi-static compression, accompanied
      by the formation of Ni-Al intermetallic compounds. In the Al-Ni-PTFE system, the
      reaction between Al and PTFE preceded the reaction between Al and Ni and the
      feasibility of increasing the energy density and damage effect of the Al-Ni-PTFE
      reactive material by means of Ni-Al reaction was proved.

PMID- 30223609
TI  - Sensor-Based Real-Time Detection in Vulcanization Control Using Machine Learning
      and Pattern Clustering.
AB  - Recent paradigm shifts in manufacturing have resulted from the need for a smart
      manufacturing environment. In this study, we developed a model to detect
      anomalous signs in advance and embedded it in an existing programmable logic
      controller system. For this, we investigated the innovation process for smart
      manufacturing in the domain of synthetic rubber and its vulcanization process, as
      well as a real-time sensing technology. The results indicate that only analysis
      of the pattern of input variables can lead to significant results without the
      generation of target variables through manual testing of chemical properties. We
      have also made a practical contribution to the realization of a smart
      manufacturing environment by building cloud-based infrastructure and models for
      the pre-detection of defects.

PMID- 30223608
TI  - A Versatile Method for Depth Data Error Estimation in RGB-D Sensors.
AB  - We propose a versatile method for estimating the RMS error of depth data provided
      by generic 3D sensors with the capability of generating RGB and depth (D) data of
      the scene, i.e., the ones based on techniques such as structured light, time of
      flight and stereo. A common checkerboard is used, the corners are detected and
      two point clouds are created, one with the real coordinates of the pattern
      corners and one with the corner coordinates given by the device. After a
      registration of these two clouds, the RMS error is computed. Then, using curve
      fittings methods, an equation is obtained that generalizes the RMS error as a
      function of the distance between the sensor and the checkerboard pattern. The
      depth errors estimated by our method are compared to those estimated by state-of
      the-art approaches, validating its accuracy and utility. This method can be used
      to rapidly estimate the quality of RGB-D sensors, facilitating robotics
      applications as SLAM and object recognition.

PMID- 30223610
TI  - Thermomechanical Noise Characterization in Fully Monolithic CMOS-MEMS Resonators.
AB  - We analyzed experimentally the noise characteristics of fully integrated CMOS
      MEMS resonators to determine the overall thermomechanical noise and its impact on
      the limit of detection at the system level. Measurements from four MEMS resonator
      geometries designed for ultrasensitive detection operating between 2-MHz and 8
      MHz monolithically integrated with a low-noise CMOS capacitive readout circuit
      were analyzed and used to determine the resolution achieved in terms of
      displacement and capacitance variation. The CMOS-MEMS system provides
      unprecedented detection resolution of 11 yF.Hz-1/2 equivalent to a minimum
      detectable displacement (MDD) of 13 fm.Hz-1/2, enabling noise characterization
      that is experimentally demonstrated by thermomechanical noise detection and
      compared to theoretical model values.

PMID- 30223611
TI  - Effect of Ti Transition Layer Thickness on the Structure, Mechanical and Adhesion
      Properties of Ti-DLC Coatings on Aluminum Alloys.
AB  - Multilayers of Ti doped diamond-like carbon (Ti-DLC) coatings were deposited on
      aluminum alloys by filtered cathodic vacuum arc (FCVA) technology using C2H2 as a
      reactive gas. The effect of different Ti transition layer thicknesses on the
      structure, mechanical and adhesion properties of the coatings, was investigated
      by scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoelectron
      spectroscopy (XPS), nanoindentation and a scratch tester. The results showed that
      the Ti transition layer could improve interfacial transition between the coating
      and the substrate, which was beneficial in obtaining excellent adhesion of the
      coatings. The Ti transition layer thickness had no significant influence on the
      composition and structure of the coatings, whereas it affected the distortion of
      the sp2-C bond angle and length. Nanoindentation and scratch test results
      indicated that the mechanical and adhesion properties of the Ti-DLC coatings
      depended on the Ti transition layer thickness. The Ti transition layer proved
      favorable in decreasing the residual compressive stress of the coating. As the Ti
      transition layer thickness increased, the hardness value of the coating gradually
      decreased. However, its elastic modulus and adhesion exhibited an initial
      decrease followed by an increasing fluctuation. Among them, the Ti-DLC coating
      with a Ti transition layer thickness of 1.1 MUm exhibited superior mechanical
      properties.

PMID- 30223613
TI  - Performance of Rayleigh-Based Distributed Optical Fiber Sensors Bonded to
      Reinforcing Bars in Bending.
AB  - Distributed Optical Fiber Sensors (DOFSs), thanks to their multiple sensing
      points, are ideal tools for the detection of deformations and cracking in
      reinforced concrete (RC) structures, crucial as a means to ensure the safety of
      infrastructures. Yet, beyond a certain point of most DOFS-monitored experimental
      tests, researchers have come across unrealistic readings of strain which prevent
      the extraction of further reliable data. The present paper outlines the results
      obtained through an experimental test aimed at inducing such anomalies to isolate
      and identify the physical cause of their origin. The understanding of such a
      phenomenon would enable DOFS to become a truly performant strain sensing
      technique. The test consists of gradually bending seven steel reinforcement bars
      with a bonded DOFS under different conditions such as different load types,
      bonding adhesives, bar sections and more. The results show the bonding adhesives
      having an influence on the DOFS performance but not on the rise of anomalies
      while the reasons triggering the latter are narrowed down from six to two,
      reaching a strain threshold and a change in structure's deformative behavior.
      Further planned research will allow identification of the cause behind the rise
      of strain-reading anomalies.

PMID- 30223612
TI  - Isolation, Characterization, and Pharmaceutical Applications of an
      Exopolysaccharide from Aerococcus Uriaeequi.
AB  - Many marine bacteria secrete exopolysaccharides (EPSs), which are made up of a
      substantial component of the macro-molecules surrounding cells. Recently, the
      wide demand for EPSs for food, cosmetics, pharmaceutical and other applications
      has led to great interest in them. In this study, an EPS produced by marine
      bacteria Aerococcus uriaeequi HZ strains (EPS-A) was isolated and purified to
      examine its structure and biological function. The molecular weight of EPS-A
      analyzed by high-performance liquid gel filtration chromatography (HPGFC) is
      found to have a number average of 2.22 * 105 and weight average of 2.84 * 105,
      respectively. High-performance liquid chromatography (HPLC) and Fourier-transform
      infrared (FT-IR) analysis indicate that EPS-A was a polysaccharide composed of
      glucose and a little mannose. In addition, the flocculating rate of sewage of EPS
      A was 79.90%. The hygroscopicity studies showed that hygroscopicity of EPS-A was
      higher than chitosan but lower than that of sodium hyaluronate. The moisture
      retention of EPS-A showed similar retention activity to both chitosan and sodium
      hyaluronate. EPS-A also can scavenge free radicals including both OH* free
      radical and O2*- free radical and the activity to O2*- free radical is similar to
      vitamin C. Safety assessment on mice indicated that the EPS-A is safe for
      external use and oral administration. EPS-A has great potential for applications
      in medicine due to its characteristics mentioned above.

PMID- 30223614
TI  - Fast and Stable Ionic Electroactive Polymer Actuators with PEDOT:PSS/(Graphene-Ag
      Nanowires) Nanocomposite Electrodes.
AB  - Ionic electroactive polymer (IEAP) actuators that are driven by electrical
      stimuli have been widely investigated for use in practical applications. However,
      conventional electrodes in IEAP actuators have a serious drawback of poor
      durability under long-term actuation in open air, mainly because of leakage of
      the inner electrolyte and hydrated cations through surface cracks on the metallic
      electrodes. To overcome this problem, a top priority is developing new high
      performance ionic polymer actuators with graphene electrodes that have superior
      mechanical, electrical conductivity, and electromechanical properties. However,
      the task is made difficultby issues such as the low electrical conductivity of
      graphene (G). The percolation network of silver nanowires (Ag-NWs) is believed to
      enhance the conductivity of graphene, while poly(3,4
      ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), which exhibits
      excellent stability under ambient conditions, is expected to improve the
      actuation performance of IEAP actuators. In this study, we developed a very fast,
      stable, and durable IEAP actuator by employing electrodes made of a nanocomposite
      comprising PEDOT:PSS and graphene-Ag-NWs (P/(G-Ag)). The cost-effective P/(G-Ag)
      electrodes with high electrical conductivity displayed a smooth surface resulting
      from the PEDOT:PSS coating, which prevented oxidation of the surface upon
      exposure to air, and showedstrong bonding between the ionic polymer and the
      electrode surface. More interestingly, the proposed IEAP actuator based on the
      P/G-Ag electrode can be used in active biomedical devices, biomimetic robots,
      wearable electronics, and flexible soft electronics.

PMID- 30223616
TI  - Thermodynamic Aspects in Non-Ideal Metal Membranes for Hydrogen Purification.
AB  - In this paper, an overview on thermodynamic aspects related to hydrogen-metal
      systems in non-ideal conditions is provided, aiming at systematically merging and
      analyzing information achieved from several different studies present in the open
      literature. In particular, the relationships among inner morphology, dissolved
      hydrogen and internal stresses are discussed in detail, putting in evidence the
      conformation complexity and the various types of dislocations induced by the
      presence of H-atoms in the lattice. Specifically, it is highlighted that the
      octahedral sites are preferentially occupied in the FCC metals (such as
      palladium), whereas tetrahedral sites are more energetically favored in BCC
      structured ones (such as vanadium). These characteristics are shown to lead to a
      different macroscopic behavior of the two classes of metals, especially in terms
      of solubility and mechanical failure due to the consequent induced stresses.
      Furthermore, starting from the expression of the chemical potential generally
      presented in the literature, a new convenient expression of the activity of the H
      atoms dissolved into the metal lattice as a function of the H-concentration is
      achieved. Such an activity expression is then used in the dissolution equilibrium
      relationship, which is shown to be the overall result of two different phenomena:
      (i) dissociative adsorption of molecular hydrogen onto the surface; and (ii)
      atomic hydrogen dissolution from the surface to the metal bulk. In this way, the
      obtained expression for equilibrium allows a method to calculate the equilibrium
      composition in non-ideal conditions (high pressure), which are of interest for
      real industrial applications.

PMID- 30223615
TI  - Beneficial Effects of Tomato Juice Fermented by Lactobacillus Plantarum and
      Lactobacillus Casei: Antioxidation, Antimicrobial Effect, and Volatile Profiles.
AB  - Tomato juice was fermented by Lactobacillus plantarum and Lactobacillus casei to
      produce an innovative high-bioactivity probiotic beverage. The levels of
      lycopene, total carotenoids, ascorbic acid, total phenolic and volatile
      compounds, 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-3-ethylbenzotiazo
      line-6-sulfonic acid (ABTS) radical scavenging capacities, ferric reducing
      antioxidant power (FRAP), and Escherichia coli flora, as well as the inhibition
      of copper-induced human low-density lipoproteins (LDL)-cholesterol oxidation
      assays, were measured. The results revealed that the ABTS and DPPH inhibition
      values, as well as the FRAP and total phenolic content, were significantly
      increased. LDL-cholesterol oxidation was markedly delayed after the addition of
      the fermented juice. The in vitro inhibitory effects of Escherichia coli flora
      were substantially increased after being fermented with Lactobacillus plantarum
      and Lactobacillus casei. The results associated with the volatile compounds
      indicated that fermentation with Lactobacillus plantarum and Lactobacillus casei
      is a meaningful strategy for modifying flavors.

PMID- 30223617
TI  - Taguchi Grey Relational Analysis for Multi-Response Optimization of Wear in Co
      Continuous Composite.
AB  - Co-continuous composites have potential in friction and braking applications due
      to their unique tribological characteristics. The present study involves Taguchi
      grey relational analysis-based optimization of wear parameters such as applied
      load, sliding speed and sliding distance, and their effect on dry sliding wear
      performance of AA6063/SiC co-continuous composite manufactured by gravity
      infiltration. A Taguchi L9 orthogonal array was designed and nine experimental
      runs were performed based on the designed experiments. The coefficient of wear
      and specific wear rate were recorded for each experiment. Based on the average
      responses computed from Taguchi grey relational analysis, an applied load of 60
      N, sliding speed of 1 m/s and sliding distance of 1000 m were estimated to be the
      optimal parameters. An Analysis of Variance (ANOVA) was conducted to identify the
      predominant factor and established all the three factors as being significant.
      The sliding distance was found to have the highest significant influence of
      61.05% on the wear of the C4 composite. Confirmation experiments conducted using
      the optimal parameters indicated an improvement of 35.25% in grey relational
      grade. Analysis of the worn surfaces of the confirmation experiment revealed
      adhesive and abrasive wear as the governing mechanisms.

PMID- 30223618
TI  - Detection of Caries Around Resin-Modified Glass Ionomer and Compomer Restorations
      Using Four Different Modalities In Vitro.
AB  - The aim of this study was to evaluate the ability of visual examination
      (International Caries Detection and Assessment System-ICDAS II), light-emitting
      diodes (LED) fluorescence (SPECTRA), laser fluorescence (DIAGNODent, DD),
      photothermal radiometry and modulated luminescence (PTR-LUM, The Canary System,
      CS) to detect natural decay beneath resin-modified glass ionomer (RMGIC) and
      compomer restorations in vitro. Twenty-seven extracted human molars and
      premolars, consisting of 2 control teeth, 10 visually healthy/sound and 15 teeth
      with natural cavitated lesions, were selected. For the carious teeth, caries was
      removed leaving some carious tissue on one wall of the preparation. For the sound
      teeth, 3 mm deep cavity preparations were made. All cavities were restored with
      RMGIC or compomer restorative materials. Sixty-eight sites (4 sites on sound
      unrestored teeth, 21 sound sites and 43 carious sites with restorations) were
      selected. CS and DD triplicate measurements were done at 2, 1.5, 0.5, and 0 mm
      away from the margin of the restoration (MOR). SPECTRA images were taken, and two
      dentists provided ICDAS II scoring for the restored surfaces. The SPECTRA data
      and images were inconclusive due to signal interference from the restorations.
      Visual examinations of the restored tooth surfaces were able to identify 5 of the
      15 teeth with caries. In these situations, the teeth were ranked as having ICDAS
      II 1 or 2 rankings, but they could not identify the location of the caries or
      depth of the lesion. CS and DD were able to differentiate between sound and
      carious tissue at the MOR, but larger variation in measurement, and poorer
      accuracy, was observed for DD. It was concluded that the CS has the potential to
      detect secondary caries around RMGIC and compomer restorations more accurately
      than the other modalities used in this study.

PMID- 30223620
TI  - Paediatric Home Artificial Nutrition in Italy: Report from 2016 Survey on Behalf
      of Artificial Nutrition Network of Italian Society for Gastroenterology,
      Hepatology and Nutrition (SIGENP).
AB  - : Home Artificial Nutrition (HAN) is a safe and efficacious technique that
      insures children's reintegration into the family, society and school.
      Epidemiological data on paediatric HAN in Italy are not available. AIM: to detect
      the prevalence and incidence of Home Parenteral Nutrition (HPN) and Home Enteral
      Nutrition (HEN), either via tube or mouth, in Italy in 2016. MATERIALS AND
      METHODS: a specific form was sent to all registered SIGENP members and
      investigators of local HAN centres, inviting them to provide the requested
      centre's data and demographics, underlying diseases and HAN characteristics of
      the patients. RESULTS: we recorded 3403 Italian patients on HAN aged 0 to 19
      years from 22 centres: 2277 HEN, 950 Oral Nutritional Supplements (ONS) and 179
      HPN programs. The prevalence of HEN (205 pts/million inhabitants) and HPN (16
      pts/million inhabitants) has dramatically increased in Italy in the last 9 years.
      Neurodisabling conditions were the first indication for HEN by tube or mouth
      while HPN is mainly requested in digestive disorders. CONCLUSIONS: HAN is a
      widespread and rapidly growing treatment in Italy, as well as in other European
      countries. Awareness of its extent and characteristics helps improving HAN
      service and patients' quality of life.

PMID- 30223619
TI  - Molecular Mechanism and Health Role of Functional Ingredients in Blueberry for
      Chronic Disease in Human Beings.
AB  - Functional ingredients in blueberry have the best health benefits. To obtain a
      better understanding of the health role of blueberry in chronic disease, we
      conducted systematic preventive strategies for functional ingredients in
      blueberry, based on comprehensive databases, especially PubMed, ISI Web of
      Science, and CNKI for the period 2008-2018. Blueberry is rich in flavonoids
      (mainly anthocyanidins), polyphenols (procyanidin), phenolic acids, pyruvic acid,
      chlorogenic acid, and others, which have anticancer, anti-obesity, prevent
      degenerative diseases, anti-inflammation, protective properties for vision and
      liver, prevent heart diseases, antidiabetes, improve brain function, protective
      lung properties, strong bones, enhance immunity, prevent cardiovascular diseases,
      and improve cognitive decline. The anthocyanins and polyphenols in blueberry are
      major functional ingredients for preventive chronic disease. These results
      support findings that blueberry may be one of the best functional fruits, and
      further reveals the mechanisms of anthocyanins and polyphenols in the health role
      of blueberry for chronic disease. This paper may be used as scientific evidence
      for developing functional foods, nutraceuticals, and novel drugs of blueberry for
      preventive chronic diseases.

PMID- 30223623
TI  - Ultrastructure of the sacculus and lagena in a moray eel (Gymnothorax sp.).
AB  - The ultrastructure of the sacculus and lagena of a moray eel, Gymnothorax sp.,
      was investigated using scanning and transmission electron microscopy. Particular
      emphasis was placed on the orientation of the sensory hair cells and on the
      ultrastructure of the sensory cells. The ciliary bundles on the sensory hair
      cells are of several types, each having a different size relationship between the
      kinocilium and stereocilia. The cell bodies of the sensory cells are similar to
      the mammalian type II sensory cell. There were no apparent differences in the
      cell bodies between sensory cells with different ciliary bundles. Hair cell
      orientation patterns on the saccular and lagenar maculae differ from patterns
      found in other fishes. The posterior side of the saccular macula in Gymnothorax
      has cells oriented dorsally and ventrally, as is typical in other non
      ostariophysan species. The anterior end of the saccular macula has alternating
      groups of anteriorly and posteriorly oriented cells, a situation that differs
      from the more typical pattern in which anteriorly oriented cells are found on the
      ventral side of the macula while posteriorly oriented cells cover the dorsal side
      of the macula. The orientation of cells on the lagena includes ventral cells that
      are located above a group of dorsally oriented cells. In many other non
      ostariophysans, ventrally oriented cells are generally posterior to the dorsally
      oriented cells.

PMID- 30223622
TI  - The Decreasing Trend in Dietary Glycaemic Index and Glycaemic Load in Australian
      Children and Adolescents between 1995 and 2012.
AB  - This study aims to examine whether there were changes between 1995-2012 in the
      dietary glycaemic index (dGI) and glycaemic load (dGL) in Australian children
      (<16 years) according to three national surveys in 1995 (1995NS), 2007 (2007NS),
      and 2011-2012 (2012NS). Glycaemic index (GI) values of foods were assigned using
      published methodology. Plausible 24-h recall data from the 1995NS, 2007NS and
      2012NS (weighted n = 2475, 4373 and 1691 respectively) were compared for
      differences in dGI and dGL, and the contribution to dGL from different foods
      using one-way ANOVA with Bonferroni post hoc comparisons and linear regression.
      Decreasing trends across surveys were found in dGI and dGL (p < 0.001). Between
      1995 and 2012, dGI and dGL per Megajoule (MJ) dropped by 2% and 6% respectively.
      The per capita dGL contribution from breads and bread rolls, fruit and vegetable
      juices, sweetened beverages and potatoes showed strong decreasing trends (R2 >
      0.7). Our findings suggest that dGI and dGL of Australian youths declined between
      1995 to 2012, which may be due to increased awareness of the GI concept and
      healthy diet, widened food choices and immigrants with diverse dietary habits.
      This may lower the future risks of chronic degenerative diseases in Australian
      youths.

PMID- 30223621
TI  - Insights into the Influence of Specific Splicing Events on the Structural
      Organization of LRRK2.
AB  - Leucine-rich repeat kinase 2 (LRRK2) is a large protein of unclear function. Rare
      mutations in the LRRK2 gene cause familial Parkinson's disease (PD) and
      inflammatory bowel disease. Genome-wide association studies (GWAS) have revealed
      significant association of the abovementioned diseases at the LRRK2 locus. Cell
      and systems biology research has led to potential roles that LRRK2 may have in PD
      pathogenesis, especially the kinase domain (KIN). Previous human expression
      studies showed evidence of mRNA expression and splicing patterns that may
      contribute to our understanding of the function of LRRK2. In this work, we
      investigate and identified significant regional differences in LRRK2 expression
      at the mRNA level, including a number of splicing events in the Ras of complex
      protein (Roc) and C-terminal of Roc domain (COR) of LRRK2, in the substantia
      nigra (SN) and occipital cortex (OCTX). Our findings indicate that the
      predominant form of LRRK2 mRNA is full length, with shorter isoforms present at a
      lower copy number. Our molecular modelling study suggests that splicing events in
      the ROC/COR domains will have major consequences on the enzymatic function and
      dimer formation of LRRK2. The implications of these are highly relevant to the
      broader effort to understand the biology and physiological functions of LRRK2,
      and to better characterize the role(s) of LRRK2 in the underlying mechanism
      leading to PD.

PMID- 30223624
TI  - An ultrastructural study of the regenerating breast feather of the fowl.
AB  - The developmental morphology of regenerating male breast feathers of the jungle
      fowl was studied at the ultrastructural level. The process of keratinization was
      observed in the three types of cells which form feather barbs: barbule cells,
      cortical cells, and medulla cells. Keratinization first became evident in the
      barbule cells and resembled the process of keratinization as observed in hair
      cortical cells and embryonic down feathers. Eventually the whole cytoplasmic area
      of the barbule cell was occupied by keratin. The barb cortex cells became
      keratinized in a similar fashion as the barbule cells but not until they were
      developmentally twice as old as the barbule cells. When keratinization was
      complete in these cells, the keratin was in the form of large agglomerates
      scattered in the cytoplasm. The barb medulla cells showed no obvious signs of
      keratinization until they were developmentally three times as old as the barbule
      cells. Keratin filament bundles were first seen near the plasma membranes of the
      medulla cells. Large empty vacuoles appeared in the cytoplasm which also
      contained moderate amounts of glycogen.

PMID- 30223625
TI  - Ultrastructure of the type "B" cells in the rectal pad epithelium of Locusta
      migratoria.
AB  - The electron microscopical structure of the type "B" cells in the rectal pad
      epithelium of Locusta is described. The type "B" cells occur singly in the distal
      region of the rectal pad epithelium. They are characteristically goblet shaped
      and join with contiguous type "A" or rectal pad cells, near the apical surface by
      means of a restricted region of septate desmosomes. Type "B" cells possess a
      microvillate apical membrane, with the villi arranged as a rosette overlying the
      apical inaginations of adjacent type "A" cells. Large numbers of microtubules and
      vacuoles of various sizes containing an assortment of inclusions are present in
      the apical region of the type "B" cells. Many of the microtubules insert distally
      on hemidesmosomes located in the apical plasma membrane. Rough endoplasmic
      reticulum and mitochondria are also present but neither are abundant. The
      possible significance of these findings is discussed.

PMID- 30223626
TI  - A histological study of wound healing and hemocyte function in the wax-moth
      Galleria mellonella.
AB  - The stages in wound healing of the wax-moth, Galleria mellonella, were examined
      using routine histological techniques. Final instar larvae were wounded and
      maintained for up to 72 hours before fixation, dehydration and embedding in
      Paraplast wax or Araldite. Immediately after wounding both fat-body and hemolymph
      were forced through the wound to form a plug. Concomitantly, the hemolymph
      coagulated forming vast networks of strand-like material attached to the
      hemocytes underlying the wound. After one to two hours this plug melanized and
      the cells became highly necrotic. Six hours after wounding, there was a massive
      influx of hemocytes which eventually attached to the melanized layer over the
      wound to form a multicellular sheath. Twelve to twenty-four hours later, the
      epidermal cells underlying the broken cuticle detached and migrated across the
      wound to form a new intact layer. This layer secreted an amorphous material which
      is probably the precursor of the new cuticle. Hemocyte functions during wound
      healing and other cellular defenses are discussed.

PMID- 30223627
TI  - Comparative analysis of the intrinsic leg musculature of the American cockroach,
      Periplaneta americana (L.).
AB  - The American cockroach has a total of 368 muscles inserting on the post-coxal
      segments of its legs. By using a narrow morphological definition for delimiting
      individual muscles, it is shown (i) that the protrochanteral musculatures (23
      muscles/leg) differ from the essentially identical meso- and metatrochanteral
      musculatures (24 and 26 muscles/leg) in number and disposition of extensors and
      in having a completely different flexor composition, and (ii) that the
      musculatures of the more distal segments of the legs are completely serially
      homologous, there being 2 muscles for moving each femur, 23 for each tibia, 7 for
      each first tarsomere, and 5 for each of the paired pretarsal claws. In all six
      legs, the trochanteral and tibial musculatures each contain single slender
      muscles that may be acting proprioceptively to measure the angular displacements
      between, respectively, the coxas and trochanters, and the femurs and tibias.
      Neurological and phylogenetic considerations are used to demonstrate why a narrow
      morphological definition should be employed, and why the widely used functional
      definition of Snodgrass ('35) is not only fallacious on evolutionary grounds, but
      also leads to making erroneous conclusions regarding the manner in which insect
      musculature is controlled by the insect central nervous system. Finally, it is
      hypothesized that the physiological limitations imposed by having an open
      circulatory system and the problems inherent in the neural control of large
      muscles may have been major evolutionary factors in forcing insects to use many
      slender muscles to control their body movements.

PMID- 30223628
TI  - Cell renewal in the epithelium of the alimentary tract of the larval lamprey,
      Petromyzon marinus L.
AB  - Light microscopic autoradiography with 3 H-thymidine demonstrates that the three
      regions of the alimentary tract in the larval (ammocoete) lamprey, Petromyzon
      marinus L., possess different patterns for renewing their epithelium. In the
      oesophagus, columnar and mucous cells originate from stem cells located at the
      bases of folds and migrate to the tops of the folds where they are apparently
      extruded. Ciliated cells, located only at the tops of the folds, seem to
      differentiate from migrating columnar cells. In the anterior intestine, stem
      cells are present throughout the epithelium so that there is limited migration of
      cells and their extrusion occurs randomly. In the posterior intestine, the stem
      cells located at the bases of the typhlosole provide a continuous population that
      differentiates and migrates to the top of the typhlosole and to the opposite
      epithelial wall where they are presumably extruded. The rates of cell renewal in
      all three epithelial regions of the alimentary tract are slower in animals
      maintained at 10 +/- 1 degrees C compared with those kept at 21 +/- 1 degrees C.
      Comparatively, ammocoetes have the least specialized system for cell renewal
      known in the alimentary tract of a vertebrate.

PMID- 30223629
TI  - Body wall morphology of Pentapora foliacea (Ellis and Solander) (Bryozoa,
      Cheilostomata).
AB  - The ascophoran Pentapora foliacea was studied from epoxy sections of skeletal and
      soft (hard-soft) tissues. The basal wall is double, indicating the colony grew as
      two independent layers, back to back. The structure of the vertical walls and
      interzooidal communication organs indicates that zooids were budded in the usual
      way as in most encrusting cheilostomes. Secondary layers of the frontal wall are
      of acicular aragonite. The ovicell develops as a flattened cuticular bladder in
      early ontogeny; the aragonitic layer of the frontal wall later engulfs it. A
      median vesicle, an evagination of the vestibular wall, is present but the eggs
      may be supplied with sufficient yolk to nurture the embryo. The overall ovicell
      structure is similar to that of hyperstomial ovicells in other cheilostomes.

PMID- 30223630
TI  - Coelomic pouch formation in the starfish Pisaster ochraceus (Echinodermata:
      Asteroidea).
AB  - The process of coelomic pouch formation in Pisaster ochraceus was studied with
      light microscopy, transmission and scanning electron microscopy and time-lapse
      cinemicrography as well as with the drug cytochalasin B. As in most asteroids,
      the paired coelomic pouches of Pisaster ochraceus are formed from outpocketing of
      the archenteron. Arrays of 50 A microfilaments are found in the presumptive
      coelomic pouch cells at the apex of the archenteron as well as in the filopodia
      of the mesenchyme cells. Both cell types undergo active movements throughout the
      entire process. Treatment of embryos with cytochalasin B (CCB) during coelomic
      pouch formation results in the loss of cell movements and the regression of the
      coelomic pouches; this is accompanied by the loss of microfilament arrays in both
      cell types. Cell movements and microfilament arrays reappear on removal of CCB
      and coelomic pouch formation resumes. Our evidence suggests that the
      microfilaments in the presumptive coelomic pouch cells provide the main force for
      the outpocketing movement. The major role of the microfilament arrays in the
      filopodia of the mesenchyme cells associated with the coelomic pouches is to
      determine the definitive shape and location of the pouches.

PMID- 30223631
TI  - A histological study of the long-term response to trauma of squamate integument.
AB  - Scale neogenesis following excision of pieces of skin of various sizes and shapes
      has been studied in several squamate species. In small wounds, neogenesis does
      not occur, the wound region contracts, and increased areas of hinge
      differentiation are seen. In large wounds, the time taken for neogenesis to
      occur, and the size, shape, distribution, and number of the reformed units, are
      variable. We confirm previous reports that neogenesis accompanies a renewal phase
      of the shedding cycle, and suggests that this is because both types of
      morphogenesis require germinal stability. All types of trauma thus far studied
      show the initial formation of a hyperplastic wound epithelium with the
      histological characteristics of a normal alpha-layer: such tissues are the basis
      for physiological barrier functions. The mechanical functions of the skin can be
      fairly adequately restored even by abnormal neogenic scales. The observed
      variability in the process of scale neogenesis, and the final form of the
      individual units, are argued to be the result of mechanical factors impinging on
      the differentiating tissues.

PMID- 30223632
TI  - Ultrastructure of the somatic portion of the gonads in asteroids, with emphasis
      on flagellated-collar cells and nutrient transport.
AB  - Somatic portions of gonads in two phanerozonian sea-stars, Ctenodiscus crispatus
      and Hippasteria phrygiana, were similar in all aspects of gross structure and
      histology seen previously in both forcipulate and spinulosan asteroids. For the
      first time, detailed ultrastructural observations have been made of cells and
      tissues that reveal several features believed to be of universal occurrence in
      the gonads of asteroids. These include flagellated-collar cells in the visceral
      peritoneum and other coelomically derived epithelia, muscular-flagellated-collar
      cells in the visceral peritoneum and genital coelomic (perihaemal) sinus, the
      digestion of collagen fibers by cells in the connective tissue layer, and the
      intimate relationship of the genital haemal sinus and the entire germinal
      epithelium. Structural and functional compartmentalization are discussed in
      relation to major activities of the gonad throughout the annual reproductive
      cycle. The distinctive ultrastructure and current generation of flagellated
      collar cells found in the visceral peritoneum are analyzed relative to their role
      in nutrient transport to gonadal tissues. The single flagellum of each
      flagellated-collar cell beats in coordination with those on neighboring cells to
      produce extremely rapid, oriented currents of coelomic fluid. The form of beating
      in an individual flagellum is planar, and the resulting synchronized activity of
      many adjacent flagella is non-metachronal; both of these characteristic aspects
      of current production have, thus far, been encountered together only in the
      Echinodermata. Flagellated-collar cells are efficient in generating currents
      which mix contents of the coelomic fluid, and they can presumably supply
      themselves with nutrients. It is concluded that nutrients so obtained are
      generally not passed through the wall of the gonad to the germinal epithelium
      and, as a result, have little to do with nutrition of somatic and germinal cells
      of the germinal epithelium. Alternatively, well-developed genital portions of the
      haemal system of the sea-star are advanced as the major channels supplying
      nutrients to germinal epithelia during gametogenesis.

PMID- 30223633
TI  - Estimating Passive Stress Acting on a Grain Entrapment Victim's Chest.
AB  - Grain entrapments remain a major concern in the grain industry, with 1,100
      incidents documented since the 1970s. One particular concern is the ability of a
      victim to breathe while entrapped in grain. Anecdotal reports suggest that
      victims struggle to breathe when entrapped in grain to a depth that covers their
      chests, yet some evidence indicates that victims should be able to breathe
      normally as long as their airways are not blocked regardless of depth. The
      hypothesis for this discrepancy is that previously published experiments measured
      an active stress state in the grain, while a person breathing also experiences a
      passive stress state during inhalation. The passive stress is significantly
      larger than the active stress. The objective of this study was to measure the
      passive stress when pushing against grain, such as during inhalation, and compare
      it to active stress state measurements. An MTS Criterion testing machine, which
      is a force deformation testing device, was used to push a block horizontally
      against a column of grain and record the force and displacement during the
      movement. The measured passive stress was calculated from the force and
      displacement values and ranged from 9.4 to 11.0 kPa at a depth of 20 to 30 cm.
      These values are three to four times larger than previously published
      measurements of stresses at similar depths. This result indicates that the
      discrepancy between experimental results and anecdotal reports is most likely due
      to the type of stress state experienced in grain entrapment. Findings imply that
      the pressures on the victim's chest during entrapment are sufficient to cause
      breathing difficulties or crush/positional asphyxiation in some cases. A full
      scale study is recommended.

PMID- 30223634
TI  - Current Grain Storage and Safety Practices of Ohio Cash Grain Operators.
AB  - Hazards associated with grain storage facilities are a contributing factor to
      agricultural injuries and are a perpetual problem for Ohio farmers, especially as
      on-farm grain storage facilities continue to grow in popularity with producers.
      To establish effective injury prevention programs, safety professionals must
      first understand how the industry operates, the culture of the workers, and the
      current practices used to avoid injuries. This research project was designed to
      bridge the gap between what is currently known about the hazards that exist on
      Ohio's farms, specifically how safety and health information is incorporated at
      the grain handling and storage facilities. Using a four-part survey, 182 cash
      grain operators, comprising a convenience sample of farmers attending educational
      events, were surveyed to determine the type of grain storage and handling
      facilities used on their farms, the occurrence of out-of-condition grain, and the
      health and safety factors practiced at these facilities, including their
      knowledge about potential hazards. Results indicated that the farmers preferred
      to get safety knowledge from a course or seminar (53.6%) or by reading a magazine
      or periodical (38.8%). The surveyed farmers indicated that they had higher
      knowledge of the safety risks of out-of-condition grain than of the health
      effects from exposure to out-of-condition grain (p < 0.01). They identified
      personal protective equipment (PPE) as their primary measure to prevent injuries,
      with the top PPE items being respirators, safety glasses, hearing protection, and
      gloves. Farmers who encountered out-of-condition grain reported more employees on
      their farms compared to the other farmers in the sample and reported higher use
      of PPE. While these results cannot be generalized to Ohio's entire population of
      cash grain farmers, they provide a good understanding of the on-farm grain
      storage and management practices, which will allow a more targeted intervention
      plan, both in better engineering controls and in future outreach programs.

PMID- 30223635
TI  - Mobile Elevated Work Platforms versus Ladders in Olive Tree Pruning: Evaluation
      of Physical Activity and Pruning Performance.
AB  - The use of mobile elevated work platforms (MEWPs) versus ladders was studied to
      evaluate the physical activity (PA) of workers and their performance during olive
      tree pruning. Accelerometers worn by the workers were used to measure triaxial
      accelerations, which were converted into PA using Freedson's equation. The mean
      values of acceleration on the three axes for workers on ladders led to
      statistically higher results than for workers on MEWPs. The energy expenditure
      (EE) and metabolic equivalent (MET) values were statistically different (about
      1.8 times higher) for the ladder work site than for the MEWP work site. The use
      of an MEWP leads to more time spent on moderate activity (84.30%) than when using
      a ladder (71.90%) but no time on vigorous activity compared to a ladder (13.88%).
      The pruning performance was 3.8 for the MEWP and 1.4 for the ladder, while the
      labor productivity was 11.4 for the MEWP and 4.2 for the ladder. Thus, it is
      possible to reduce worker employment and costs by about 2.7 times with MEWPs.

PMID- 30223636
TI  - Preventing Human Salmonella Infections Resulting from Live Poultry Contact
      through Interventions at Retail Stores.
AB  - The number of outbreaks of Salmonella infections linked to live poultry contact
      increased from 1990 to 2016. In 2016, the number of human illnesses linked to
      live poultry was the highest reported, with more than 900 cases, including 209
      hospitalizations and three deaths. Live poultry harboring Salmonella typically
      appear healthy but can intermittently shed bacteria in their droppings,
      contaminating their feathers, beaks, and the areas where they live and roam.
      Thus, both direct contact with poultry and indirect contact with anything in
      areas where animals live and roam can result in human Salmonella infection. To
      prevent Salmonella infections linked to live poultry, a One Health approach for
      control and prevention is required. This approach unifies animal and human health
      needs and takes into account the environments at the hatcheries where poultry are
      produced, the agricultural retail stores where poultry are sold, and the
      customers who own and raise poultry. Agricultural retail stores are the main
      point of sale for backyard poultry in the U.S. Therefore, stores can play a vital
      role in preventing infections by sourcing poultry from hatcheries that take steps
      to reduce Salmonella in the environment, by displaying poultry in areas that can
      be easily cleaned, and by using barriers that allow customers to view, but not
      touch, poultry from a distance. Retail store employees also have a role in
      preventing illnesses and contamination after the sale by educating customers
      about appropriate housing for live poultry in outdoor coops, barns, or other
      designated areas.

PMID- 30223637
TI  - Stability Analysis of Agricultural Off-Road Vehicles.
AB  - Vehicle rollovers cause many agricultural work-related fatalities each year.
      Tractors, off-road utility vehicles (ORUVs), zero turn radius (ZTR) mowers, and
      all-terrain vehicles (ATVs) can all become involved in fatal rollovers. The
      rollover tendency of these vehicles was evaluated using static lateral and
      longitudinal stability angles. Center of gravity locations were measured with the
      lift axle method, and lateral and longitudinal stability angles were calculated
      for four ATVs, five ORUVs, four ZTR mowers, and four lawn tractors. Stability
      angles were calculated for loaded and unloaded vehicle conditions. Loading
      vehicles with ballast and operators can substantially decrease lateral and
      longitudinal stability angles. Stability angles for these vehicles and for five
      full-size agricultural tractors were compared. All loaded and unloaded, lateral
      and longitudinal stability angles determined met the appropriate ANSI
      requirements.

PMID- 30223638
TI  - Ambient air quality and subjective stress level using Community Health Survey
      data in Korea.
AB  - OBJECTIVES: Air pollution causes various disease in exposed populations, and can
      lead to premorbid health effects manifested as both physical and psychological
      functional impairment. The present study investigated the subjective stress level
      in daily life in relation to the level of air pollution. METHODS: Data from the
      Community Health Survey (2013), comprising 99,162 men, and 121,273 women residing
      in 253 healthcare administrative districts, were combined with air pollutant
      concentration modelling data from the Korean Air Quality Forecasting System, and
      were stratified by subjective stress levels into five strata for multiple
      logistic regression. Levels of exposure were divided into five quintiles
      according to the annual concentration of nitrogen dioxide (NO2), and were
      analyzed using a single-pollutant model using NO2 concentration only, and a multi
      pollutant model adjusted for the concentration of particulate matter <10 MUm in
      diameter. RESULTS: Analysis of men and women in various age groups showed the
      highest odds ratio (OR) for subjective stress level at the highest NO2
      concentration quintile in men and women aged 30-64 years (men: 2.91; 95%
      confidence interval [CI], 2.12 to 4.01; women: 1.82; 95% CI, 1.32 to 2.51). As
      the NO2 concentration quintile increased, the OR increased. Men showed higher ORs
      than women in all strata. CONCLUSIONS: In the present study, annual NO2
      concentrations were found to be associated with subjective stress levels. This
      association was especially clear among socioeconomically active men and women
      aged 30-64 years.

PMID- 30223639
TI  - Learning through multiple lenses: analysis of self, peer, near-peer and faculty
      assessment of a clinical history taking task in Australia.
AB  - PURPOSE: Peer assessment may offer a framework for expected skill development and
      feedback appropriate to the learner level. Near-peer (NP) assessment may elevate
      expectations and motivate student learning. Feedback from peers and NPs may offer
      a sustainable approach to enhancing student assessment feedback. The aim was to
      analyze the relationship and attitudes of self, peer, NP and faculty marking of
      an assessment. METHODS: A cross sectional study design was used. Year 2
      osteopathy students (n = 86) were invited to self and peer assess a clinical
      history-taking and communication skills assessment. Near-peers and faculty also
      marked the assessment. Year 2 students also completed a peer/NP attitudes
      questionnaire. Descriptive statistics and Spearman's rho were used to evaluate
      the relationships across marker groups. RESULTS: Year 2 students (n=9), near
      peers (n=3) and faculty (n=5) were recruited. Correlations between self and peer
      (r=0.38) and self and faculty (r = 0.43) marks were moderate. A weak correlation
      was observed between self and near-peer marks (r = 0.25). Perceptions of peer and
      near-peer marking were varied with over half of the cohort suggesting peer or NP
      assessments marks should not contribute to a grade. CONCLUSION: Framing peer and
      NP assessment as another feedback source may offer a sustainable method for
      enhancing feedback without overloading faculty resources. Multiple sources of
      feedback may assist in developing assessment literacy and calibrate a students'
      self-assessment capability. The small number of students recruited may indicate
      some acceptability of peer and NP assessment however further work is required to
      increase its acceptability.

PMID- 30223640
TI  - Study of liver in HBV-related hepatocellular carcinoma: Stereology shows
      quantitative differences in liver structure.
AB  - Hepatocellular carcinoma is one of the main consequences of liver chronic
      disease. Hepatocellular carcinoma-related changes may be seen in patients with
      chronic hepatitis B. The aim of the current study was to quantitate liver tissue
      elements by stereological technique in patients with hepatitis B-related cancer
      and compare the results with control and only hepatitis B group. Needle liver
      biopsies from 40 patients with only chronic hepatitis B infection, from 41
      patients with only early hepatocellular carcinoma, from 40 patients with early
      hepatitis B-related cancer and 30 healthy subjects (control group) were analyzed
      by stereological method using systematic uniform random sampling method.
      Haematoxylin and eosin stained sections were used. The numerical density of
      hepatocytes, hepatocyte volume, numerical density of Kupffer cells, volume
      density of the connective tissue in the portal space, and volume density of the
      connective tissue were assessed. Quantitative analysis of liver samples indicated
      that there were statistically significant differences in the numerical density of
      hepatocytes, hepatocyte volume, numerical density of Kupffer cells, volume
      density of the connective tissue in the portal space, and volume density of the
      connective tissue between control and hepatitis B-related cancer and hepatitis B
      groups. Quantitative, stereological technique is simple and reliable for
      evaluating HCC in chronic hepatitis B. It is useful for assessing the liver
      tissue parameters. Stereology is recommended for the diagnosis of people prone to
      cancer in patients with chronic hepatitis B.

PMID- 30223642
TI  - DNA Octahedron-Based Fluorescence Nanoprobe for Dual Tumor-Related mRNAs
      Detection and Imaging.
AB  - With the development of biotechnology, the detection of cancer biomarkers has
      been a promising approach for cancer diagnosis and therapy. Herein, we reported a
      DNA octahedron-based fluorescence nanoprobe, which was capable of detecting and
      imaging of two kinds of tumor-related mRNAs in living cells simultaneously. The
      DNA nanoprobe was constructed of eight single-stranded DNAs, in which two
      oligonucleotides (recognition sequences) were modified with quenchers (BHQ2 and
      BHQ3) and the adjacent sequences were modified with fluorophores (Cy3 and Cy5),
      respectively. In the presence of targets, the recognition sequences could
      dissociate from the nanoprobe skeleton by strand displacement reaction and the
      fluorescence was recovered accordingly. With the modification of AS1411 aptamer,
      the nanoprobe could internalize cancer cells more efficiently and distinguish
      cancer cells from normal cells. In addition, the nanoprobe exhibited good
      stability, biocompatibility, selectivity, and responded quickly to the targets as
      well. The DNA nanoprobe was designed in the formation of octahedron and may
      provide an inspiration for multidetection of cancer biomarkers based on the DNA
      nanotechnology.

PMID- 30223641
TI  - Assessment of Cognition in Schizophrenia Using Trail Making Test: A Meta
      Analysis.
AB  - OBJECTIVE: The present meta-analysis aimed to analyze the cognitive performance
      of schizophrenia patients measured by Trail Making Tests (TMT) and the
      contribution of socio-demographic factors to cognitive impairments. METHODS:
      PubMed and PsycARTICLES databases were searched for the studies published between
      January 1985 and November 2017. Data were drawn from 19 studies encompassing 1095
      patients and 324 controls. The effect size and heterogeneity were assessed with
      Comprehensive Meta-Analysis version 2 using random-effect model. RESULTS:
      Overall, the results showed that the schizophrenia patients performed
      significantly (p<0.001) worse than healthy controls in both TMT-A and B. However,
      concurrent substance abuse, clinical status (inpatient or outpatient), duration
      of education and duration of illness were not associated with cognitive
      impairment among the schizophrenia patients. CONCLUSION: The present meta
      analysis confirmed the cognitive processing speed and flexibility of
      schizophrenia patients were impaired. However, their duration of education,
      duration of illness and clinical status (inpatient or outpatient) were not the
      risk factors.

PMID- 30223643
TI  - Discovery of a New Pterocarpan-Type Antineuroinflammatory Compound from Sophora
      tonkinensis through Suppression of the TLR4/NFkappaB/MAPK Signaling Pathway with
      PU.1 as a Potential Target.
AB  - Neuroinflammation underlies many neuro-degenerative diseases. In this paper, we
      report the identification of a new pterocarpan-type anti-inflammatory compound
      named sophotokin isolated from Sophora tonkinensis. S. tonkinensis has been used
      traditionally for treatment of conditions related to inflammation. Our initial
      screening showed that sophotokin dose-dependently inhibits lipopolysaccharide
      (LPS)-stimulated production of NO, TNF-alpha, PGE2, and IL-1beta in microglial
      cells. This antineuroinflammatory effect was associated with sophotokin's
      blockade of LPS-induced production of the inflammatory mediators iNOS and COX-2.
      Western blot and qPCR analysis demonstrated that sophotokin inhibits both the p38
      MAPK and NF-kappaB signal pathways. Further studies revealed that sophotokin also
      suppresses the expression of cluster differentiation 14 (CD14) in the toll-like
      receptor 4 (TLR4) signaling pathway. Following down-regulation of MyD88 and
      TRAF6, sophotokin inhibits the activation of the NF-kappaB and MAPK signal
      pathways in LPS-induced BV-2 cells. In silico studies suggested that sophotokin
      could interact with PU.1-DNA complex through hydrogen binding at sites 1 and 2 of
      the complex, blocking the DNA binding. This suggests that PU.1 may be a potential
      target of sophotokin. Taken together, these results suggest that sophotokin may
      have therapeutic potential for diseases related to neuroinflammation. The
      mechanism of antineuroinflammatory effects involves inhibition of the TLR4 signal
      pathway at the sites of NF-kappaB and MAPK with PU.1 as a likely upstream target.

PMID- 30223645
TI  - The Use of Cluster Expansions To Predict the Structures and Properties of
      Surfaces and Nanostructured Materials.
AB  - The construction of cluster expansions parametrized by first-principles
      calculations is a powerful tool for calculating properties of materials. In this
      Perspective, we discuss the application of cluster expansions to surfaces and
      nanomaterials. We review the fundamentals of the cluster expansion formalism and
      how machine learning is used to improve the predictive accuracy of cluster
      expansions. We highlight several representative applications of cluster
      expansions to surfaces and nanomaterials, demonstrating how cluster expansions
      help researchers build structure-property relationships and enable rational
      design to accelerate the discovery of new materials. Potential applications and
      future challenges of cluster expansions are also discussed.

PMID- 30223644
TI  - Creation and Characterization of a Genomically Hybrid Strain in the Nitrogen
      Fixing Symbiotic Bacterium Sinorhizobium meliloti.
AB  - Many bacteria, often associated with eukaryotic hosts and of relevance for
      biotechnological applications, harbor a multipartite genome composed of more than
      one replicon. Biotechnologically relevant phenotypes are often encoded by genes
      residing on the secondary replicons. A synthetic biology approach to developing
      enhanced strains for biotechnological purposes could therefore involve merging
      pieces or entire replicons from multiple strains into a single genome. Here we
      report the creation of a genomic hybrid strain in a model multipartite genome
      species, the plant-symbiotic bacterium Sinorhizobium meliloti. We term this
      strain as cis-hybrid, since it is produced by genomic material coming from the
      same species' pangenome. In particular, we moved the secondary replicon pSymA
      (accounting for nearly 20% of total genome content) from a donor S. meliloti
      strain to an acceptor strain. The cis-hybrid strain was screened for a panel of
      complex phenotypes (carbon/nitrogen utilization phenotypes, intra- and
      extracellular metabolomes, symbiosis, and various microbiological tests).
      Additionally, metabolic network reconstruction and constraint-based modeling were
      employed for in silico prediction of metabolic flux reorganization. Phenotypes of
      the cis-hybrid strain were in good agreement with those of both parental strains.
      Interestingly, the symbiotic phenotype showed a marked cultivar-specific
      improvement with the cis-hybrid strains compared to both parental strains. These
      results provide a proof-of-principle for the feasibility of genome-wide replicon
      based remodelling of bacterial strains for improved biotechnological applications
      in precision agriculture.

PMID- 30223646
TI  - Point-of-Care Diagnoses: Flexible Patterning Technique for Self-Powered Wearable
      Sensors.
AB  - This paper demonstrated the fabrication of a facile, low-cost, and self-powered
      platform for point-of-care fitness level and athletic performance monitoring
      sensor using electrochemical lithography method and its application in body fluid
      sensing. Flexible Au/prussian blue electrode was employed as the indicating
      electrode, where the color change was an indication of fitness level and athletic
      performance. A piece of Al foil, Au/multiwalled carbon nanotubes (MWCNTs)-glucose
      dehydrogenase, and Au/polymethylene blue-MWCNTs-lactic dehydrogenase electrodes
      were used for the detection of ionic strength, glucose, and lactic acid in sweat,
      respectively, which allows the sensor to work without any extra instrumentation
      and the output signal can be recognized by the naked eyes. The advantages of
      these sensors are (1) self-powered; (2) readily applicable to the detection of
      any electroactive substance by an electrochromic material; (3) easy to fabricate
      via two steps of EDP; and (4) point-of-care. By assembling the energy and sensing
      components together through a transparent adhesive tape, the proposed self
      powered wearable biosensor exhibits superior performances, indicating its broad
      applied prospect in the point-of-care diagnoses.

PMID- 30223647
TI  - Base-Mediated Cascade Aldol Addition and Fragmentation Reactions of
      Dihydroxyfumaric Acid and Aromatic Aldehydes: Controlling Chemodivergence via
      Choice of Base, Solvent, and Substituents.
AB  - The diester derivative of dihydroxyfumaric acid (DHF) has been used exclusively
      as an electrophile in organic synthesis. However, the synthetic utility of DHF's
      nucleophilic reactivity, contained in the ene-diol moiety, has been
      underexplored. Inspired by recently observed pH-dependent chemodivergent
      nucleophilic aldol reactions of dihydroxyfumarate (DHF2-) with glyoxylate and
      formaldehyde, we report herein the control and synthetic application of base
      controlled chemodivergent reactions between dihydroxyfumarate and aromatic and
      heteroaromatic aldehydes. With hydroxide as the base in a predominantly aqueous
      medium, aldol addition followed by deoxalation occurs to provide various 3-aryl
      2,3-dihydroxypropanoic acids. With triethylamine as the base in THF, 1-aryl-2,3
      dihydroxypropanones are the products of the reaction. In order to understand the
      difference in reactivity between DHF, its dicarboxylate, and its dimethyl ester,
      we undertook computational and experimental studies that provide a rationale as
      to why the dihydroxyfumarate (DHF2-) is a nucleophile while the corresponding
      diester reacts as an electrophile.

PMID- 30223648
TI  - Predicting and Controlling Entangled Two-Photon Absorption in Diatomic Molecules.
AB  - The use of nonclassical states of light to probe organic molecules has received
      great attention due to the possibility of providing new and detailed information
      regarding molecular excitations. Experimental and theoretical results have been
      reported which show large enhancements of the nonlinear optical responses in
      organic materials due to possible virtual-electronic-state interactions with
      entangled photons. In order to predict molecular excitations with nonclassical
      light, more detailed investigations of the parameters involved must be carried
      out. In this report we investigate the details of the state-to-state parameters
      important in calculating the contribution of particular transitions involved in
      the entangled two-photon absorption process for diatomic molecules. The
      theoretical discussion of the entangled two-photon process is described for a set
      of diatomic molecules. Specifically, we provide detailed quantum chemical
      calculations which give accurate energies and transition moments for selection
      rule allowed intermediate states important in the entangled nonlinear effect for
      the diatomic molecules. These results are used to estimate in a more accurate
      manner the nonmonotonic behavior of the entangled two-photon absorption cross
      section. We also derive accurate approximations that can be used to predict the
      period between entanglement-induced transparencies without needing exact values
      of the transition dipole moments. These results suggest that with the additional
      parameters allotted by the entangled two-photon absorption (in comparison to the
      classical case), it may be possible to predict and later control the nonlinear
      absorption and transparency of a molecule at a constant incident photon
      frequency.

PMID- 30223649
TI  - Combined Proteome and Toxicology Approach Reveals the Lethality of Venom Toxins
      from Jellyfish Cyanea nozakii.
AB  - Jellyfish are a type of poisonous cnidarian invertebrate that secrete lethal
      venom for predation or defense. Human beings often become victims of jellyfish
      stings accidentally while swimming or fishing and suffer severe pain, itching,
      swelling, inflammation, shock, and even death. Jellyfish venom is composed of
      various toxins, and the lethal toxin is the most toxic and hazardous component of
      the venom, which is responsible for deaths caused by jellyfish stings and
      envenomation. Our previous study revealed many toxins in jellyfish venom,
      including phospholipase A2, metalloproteinase, and protease inhibitors. However,
      it is still unknown which type of toxin is lethal and how it works. Herein a
      combined toxicology analysis, proteome strategy, and purification approach was
      employed to investigate the lethality of the venom of the jellyfish Cyanea
      nozakii. Toxicity analysis revealed that cardiotoxicity including acute
      myocardial infarction and a significant decrease in both heart rate and blood
      pressure is the primary cause of death. Purified lethal toxin containing a
      fraction of jellyfish venom was subsequently subjected to proteome analysis and
      bioinformation analysis. A total of 316 and 374 homologous proteins were
      identified, including phospholipase A2-like toxins and metalloprotease-like
      toxins. Furthermore, we confirmed that the lethality of the jellyfish venom is
      related to metalloproteinase activity but without any phospholipase A2 activity
      or hemolytic activity. Altogether, this study not only provides a comprehensive
      understanding of the lethal mechanism of jellyfish venom but also provides very
      useful information for the therapeutic or rescue strategy for severe jellyfish
      stings.

PMID- 30223650
TI  - An Efficient Lossless Compression Algorithm for Trajectories of Atom Positions
      and Volumetric Data.
AB  - We present our newly developed and highly efficient lossless compression
      algorithm for trajectories of atom positions and volumetric data. The algorithm
      is designed as a two-step approach. In the first step, efficient polynomial
      extrapolation schemes reduce the information entropy of the data by exploiting
      both spatial and temporal continuity. The second step processes the data by a
      series of transformations (Burrows-Wheeler, move-to-front, run length encoding)
      and finally compresses the stream with multitable canonical Huffman coding. Our
      approach reaches a compression ratio of around 15:1 for typical position
      trajectories in the XYZ format. For volumetric data trajectories in Gaussian Cube
      format (such as electron density), even a compression ratio of around 35:1 is
      yielded, which is by far the smallest size of all formats compared here. At the
      same time, compression and decompression are still reasonably fast for everyday
      use. The precision of the data can be selected by the user. For storage of the
      compressed data, we introduce the BQB file format, which is very robust,
      flexible, and efficient. In contrast to most archiving formats, it allows fast
      random access to individual trajectory frames. Our method is implemented in C++
      and provided as free software under the GNU LGPL license. It has been included in
      the TRAVIS program package but is also available as stand-alone tool and as a
      library ("libbqb") for use in other projects.

PMID- 30223651
TI  - Synthesis of meso-Tetraaryl Triphyrins(2.1.1).
AB  - A simple, straightforward [2+1] condensation of 5,6-diaryldipyrroethene
      dicarbinols with pyrrole under mild acid-catalyzed conditions resulted in the
      formation of highly desirable aromatic beta-free meso-tetraaryl
      [14]triphyrins(2.1.1) in 15-18% yields. The triphyrins(2.1.1) are very novel
      monoanionic tridentate ligands that form metal complexes readily as demonstrated
      here by preparing Re(I) complexes.

PMID- 30223652
TI  - Light Controlled Optical Aharonov-Bohm Oscillations in a Single Quantum Ring.
AB  - We found that optical Aharonov-Bohm oscillations in a single GaAs/GaAlAs quantum
      ring can be controlled by excitation intensity. With a weak excitation intensity
      of 1.2 kW cm-2, the optical Aharonov-Bohm oscillation period of biexcitons was
      observed to be half that of excitons in accordance with the period expected for a
      two-exciton Wigner molecule. When the excitation intensity is increased by an
      order of magnitude (12 kW cm-2), a gradual deviation of the Wigner molecule
      condition occurs with decreased oscillation periods and diamagnetic coefficients
      for both excitons and biexcitons along with a spectral shift. These results
      suggest that the effective orbit radii and rim widths of electrons and holes in a
      single quantum ring can be modified by light intensity via photoexcited carriers,
      which are possibly trapped at interface defects resulting in a local electric
      field.

PMID- 30223653
TI  - Discovery and Characterization of 4-Hydroxy-2-pyridone Derivative Sambutoxin as a
      Potent and Promising Anticancer Drug Candidate: Activity and Molecular Mechanism.
AB  - Sambutoxin, a representative derivative of 4-hydroxy-2-pyridone, was isolated
      from Hericium alpestre for the first time in this study. The possible correlation
      between the sambutoxin-induced suppression of tumor growth and its influence on
      cell-cycle arrest and apoptosis was investigated. The effects of sambutoxin on
      reactive oxygen species (ROS) production, DNA damage, mitochondrial transmembrane
      potential, cell apoptosis, and the expression of related proteins were evaluated.
      An in vitro cell viability study demonstrated that sambutoxin could inhibit the
      proliferation of various cancer cells. Treatment with sambutoxin induced the
      production of ROS, which caused DNA damage. Furthermore, the subsequent
      sambutoxin-induced activation of ATM and Chk2 resulted in G2/M arrest,
      accompanied by decreased expression of cdc25C, cdc2, and cyclin B1. Sambutoxin
      induced apoptosis by activating the mitochondrial apoptosis pathway through an
      increased Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (DeltaPsim),
      cytochrome (Cyt) c release, caspase-9 and caspase-3 activation, and poly(ADP
      ribose) polymerase (PARP) degradation. The ROS elevation induced the sustained
      phosphorylation of c-Jun N-terminal kinase (JNK), while SP600125, a JNK
      inhibitor, nearly completely reversed sambutoxin-induced apoptosis. Accordingly,
      an in vivo study showed that sambutoxin exhibited potential antitumor activity in
      a BALB/c nude mouse xenograft model without significant systemic toxicity.
      Moreover, the expression changes in proteins related to the G2/M phase, DNA
      damage, and apoptosis in vivo were consistent with those in vitro. Importantly,
      sambutoxin has remarkable antiproliferative effects and is a promising
      anticarcinogen candidate for cancer treatment.

PMID- 30223654
TI  - Higher Symmetry Multinuclear Clusters of MOFs for Highly Selective CO2 Capture.
AB  - A new approach of finely tuning multinuclear clusters of MOFs through symmetry
      upgradingly isoreticular transformation was firstly presented and a bcu-type MOF,
      {[Cu4(MU4-O)Cl2(IN)8]*CuCl2}infinity (NJU-Bai35; NJU-Bai for Nanjing University
      Bai group), with cluster [Cu4(MU4-O)(COO)4N4Cl2] of higher symmetry com-pared to
      the pristine MOF, was successfully synthesized. The symmetry upgrading
      implemented on the inorganic part triggers the adjustment of channels in NJU
      Bai35 to fit CO2 molecules, leading to a high CO2 adsorption capacity (7.20 wt%
      at ~ 0.15 bar and 298 K) and high selectivity of CO2 over N2 and CH4 (275.8 for
      CO2/N2 and 11.6 for CO2/CH4) in NJU-Bai35. Breakthrough experiments further
      confirmed that NJU-Bai35 might be an excel-lent candidate for CO2 capture and
      natural gas purification.

PMID- 30223655
TI  - Current trends in the diagnosis and treatment of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease and its typical symptoms heartburn and
      regurgitation is one of the most common gastrointestinal disorders. Besides
      esophageal symptoms awareness of extraesophageal symptoms is increasing. The
      diagnosis is usually based on history of symptoms and on endoscopically visible
      esophageal injury in some patients. Normal endoscopic finding and refractory
      symptoms on standard treatment should evoke further examination. Proton pump
      inhibitors have been the mainstay of medical therapy. Long term maintenance
      treatment may raise awareness of side effects and therapeutic alternatives. This
      review is focused of current available diagnostic and therapeutic strategies for
      gastroesophageal reflux disease. Key words: Barrett's esophagus - esophageal
      impedance - esophageal stricture - fundoplication - gastroeso-phageal reflux -
      gastroesophageal reflux disease - proton pump inhibitors.

PMID- 30223656
TI  - Therapy for peptic ulcer disease.
AB  - The modern therapy for peptic ulcer disease and other acid peptic diseases is
      based on administration of proton pump inhibitors (PPI) which have fully replaced
      anacids, parasympatholytics and histamine H2 receptor antagonists. The most
      effective way is to administer proton pump inhibitors in the morning on an empty
      stomach in a single daily dose. It is a very safe therapy, despite the fact that
      a potential adverse effect of long-term PPI treatment on the efficacy of other
      medications (clopidogrel), on bone metabolism and development of respiratory
      infections have been discussed recently. PPI also play an essential role in the
      eradication treatment of Helicobacter pylori infection, the prevention and
      treatment of gastropathy induced by nonsteroidal anti-inflammatory drugs and in
      relation to some rare hypersecretory conditions. The role of proton pump
      inhibitors in the therapy for functional dyspepsia is contradictory. Massive
      bleeding from the peptic ulcer is a relatively frequent complication of NSAID
      gastropathy. Endoscopic hemostasis and parenteral administration of PPI for at
      least 72 hours are used in therapy. Key words: acid peptic diseases - gastric
      secretion - peptic ulcer - proton pump inhibitors.

PMID- 30223657
TI  - History of celiac disease.
AB  - Intestinal disease with prominent malabsorption resembling celiac disease was
      already described in India in the 15th century B.C. This review provides a brief
      history of celiac disease from Aretaeus of Cappadocia (1st century A.D.) to
      Willem Karel Dicke (mid 20th century). Key words: celiac disease - Dicke - Gee -
      Herter - history - sprue.

PMID- 30223658
TI  - Celiac disease in 2018.
AB  - Currently more than 50 diseases and disorders are associated with gluten and/or
      other wheat (cereals) components. Even celiac disease is not just one illness but
      a group of at least three different related entities. This review provides
      highlights of celiac disease and its differential diagnosis. Key words: allergy
      to gluten - celiac disease - gluten-associated diseases - refractory sprue.

PMID- 30223659
TI  - Diagnosis of gastrointestinal motility disorders.
AB  - Gastrointestinal motility and the effects on luminal contents that are brought
      about by it can be studied in several ways. In clinical practice, manometry
      remains one of the most important investigational techniques, in particular for
      oesophageal and anorectal disorders. Radiographic examination of bolus transit
      through the gastrointestinal tract also continues to be a valuable tool.
      Scintigraphy still is the standard for assessment of gastric emptying, but 13C
      breath tests are an alternative. Many other techniques are used mainly in the
      context of scientific research but some of these may become incorporated in the
      diagnostic armamentarium. Key words: breath tests - conventional manometry - high
      resolution manometry - radiodiagnostic methods - scintigraphy.

PMID- 30223660
TI  - Diverticular disease: diagnosis and treatment.
AB  - Diverticular disease is one of the most common gastroenterological diseases. Its
      morphological basis are diverticula, whose prevalence in adults nears 50 %, with
      25% clinical symptomatology and 5% occurrence of complications. It is a disease
      of older age, however its incidence is also rising in younger individuals, where
      it takes a more severe course. Its incidence is ascribed to a diet with a
      relatively low fibre content, however studies do not yield such clear results.
      Further risk factors include smoking, use of opiates and corticoids, obesity,
      alcoholism and smoking, hypertension, polycystosis, immunosuppression and use of
      non-steroid antiflogistics. Patients with diverticular disease also present with
      abnormal intestinal motility, intestinal dysbiosis and other physiological and
      morphological abnormalities. The most types of diverticulosis occur in the
      sigmoid colon, though especially in Asia the colon ascendens is more frequently
      affected. There are several classification schemes among which an individual
      assessment of complications is gaining in importance. The diagnosis includes
      clinical data, routine laboratory tests for inflammation, calprotectin in stool,
      coloscopy, ultrasound, CT and magnetic resonance. The basis for the treatment of
      symptomatic uncomplicated diverticular disease consists of drugs bringing
      symptomatic relief, fibre, probiotics, mesalazine and non-absorbable antibiotics,
      nonetheless the results of a number of studies are not fully convincing. The
      recommended treatment should be initiated with dietary fibre and probiotics, in
      the case of lasting problems add a non-absorbable antibiotic rifaximine with
      cyclic administration. Mild diverticulitis should essentially be treated by means
      of hydration and adjustments in the dietary regimen, antibiotics are not
      necessary when its course is uncomplicated and improvement is achieved, however
      the decision is individual and risk factors such as immunosuppression, diabetes,
      old age, pregnancy etc. Antibiotics are reserved for the treatment of severe or
      repeated diverticulitis, sepsis and complications. As prevention of further
      attacks, again probiotics, mesalazine and cyclically non-absorbable antibiotics
      are used, e,g. for a period of 10 days at monthly intervals. The proportion of
      surgeries is decreasing also where acute conditions are concerned and the
      efficiency of conservative treatment of diverticulitis is on the increase.
      Abscess should primarily be treated via non-surgical drainage. Even perforation
      and peritonitis can be treated via laparoscopic drainage without subsequent
      surgery being necessary, of course considering an overall condition an individual
      decision needs to be made. Generalized and fecal peritonitis are treated by open
      surgery. Earlier, elective resection was recommended after 2 attacks of
      diverticulitis, currently an individual approach is emphasized with respect to
      age, comorbidities and a character of the complaint and it is only indicated
      exceptionally. The proportion of laparoscopic resections is growing. The results
      are basically identical for Hartmann's procedure as well as primary resection.
      Key words: calprotecin - diverticular disease - dietary fibre - diverticulosis -
      mesalazine - non-absorbable antibiotics - probiotics.

PMID- 30223661
TI  - Familial adenomatous polyposis: complex patient management.
AB  - Familial adenomatous polyposis (FAP) is a hereditary disease characterized by
      presence of numerous colorectal adenomas. It often exposes its carrier to
      absolute risk of colorectal cancer, but also to other extracolonic tumours
      (especially to duodenal cancer and desmoid). Screening and surveillance of FAP
      patients leads to reduction of colorectal cancer incidence and mortality.
      Colonoscopy/lower endoscopy and esophagogastroduodenoscopy (including use of side
      viewing endoscope) are the principal examinations. Colectomy is the standard
      therapeutic procedure, but endoscopic therapy plays relevant role both in upper
      and lower gastrointestinal tract. Recent international guidelines and some new
      tools for severity classification enable effectively reduce the mortality related
      to this disease by individualized patient management. Key words: colorectal
      cancer - familial adenomatous polyposis.

PMID- 30223662
TI  - Conventional and biological therapy for inflammatory bowel disease.
AB  - Crohn's disease and ulcerative colitis are chronic digestive conditions incurable
      by medication or surgery, which affect mainly young populations in economically
      developed countries. A medical treatment includes conventional preparations:
      aminosalicylates, corticosteroids, immunosuppressive drugs, antibiotics and
      exceptionally also probiotics, while in not responding patients or those at
      higher risk of an adverse course a biological treatment is indicated. The most
      frequently administered biologics are antibodies directed against the tumour
      necrosis factor alpha, which are highly effective, but the length of their
      application is limited by a loss of efficiency and incidence of adverse effects.
      The new, more selectively acting biologics include anti-integrin antibodies and
      interleukin 12/23 antibodies. Key words: biological treatment - Crohn's disease -
      idiopathic bowel inflammation - medication-based treat-ment - ulcerative colitis.

PMID- 30223663
TI  - The IBD outpatient care in the clinical practice.
AB  - The number of patients with inflammatory bowel disease (Crohn's disease and
      ulcerative colitis) has increased steadily. Gastroenterology outpatient secondary
      type centres play very important role in the care for these patients. Their
      clinical practice was assessed in our study. The data was obtained using a
      structured questionnaire concerned on 4 major topics (the centre characteristics,
      diagnosis, therapy and patient's monitoring). Obtained data was compared with
      both local and international recommendations and showed high professional
      standards of care. Key words: Crohn's disease - diagnosis - inflammatory bowel
      disease - outpatient care - patient's monitoring - therapy - ulcerative colitis.

PMID- 30223664
TI  - PSC-IBD: specific phenotype of inflammatory bowel disease associated with primary
      sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a progressive disease of the biliary tree
      which represents one of the most frequent indications for orthotopic liver
      transplantation (OLTx) in developed countries. LTx is currently the only curative
      procedure for PSC. Concomitant inflammatory bowel disease (IBD) is present in
      approximately 70 % of patients with PSC. Such colitis in PSC has specific
      clinical and etiological features and is considered as a distinct phenotype of
      IBD often referred to as "PSC-IBD". The phenotype usually manifests as mild
      extensive colitis with right-sided predominance. Other morphological features,
      such as back- wash ileitis and rectal sparing, are also increasingly prevalent in
      PSC-IBD. Moreover, patients with PSC-IBD have increased risk towards developing
      colorectal neoplasia which tend to be highly progressive. Therefore, total
      colonoscopy employing multiple random biopsies or chromoendoscopy should be
      performed every 1-2 years once PSC-IBD is diagnosed. Even detection of low-grade
      dysplasia in colonic mucosa should lead towards prophylactic colectomy
      consideration in patients with PSC-IBD. Recommendations regarding pharmacological
      therapy are based on the similar principles as in Crohn's disease and ulcerative
      colitis. However, status of the liver disease should always be taken into
      account. Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is a method of
      choice in the field of surgical therapy of PSC-IBD. The clinical course of PSC
      IBD may deteriorate after OLTx despite immunosuppressive therapy administration.
      IBD can even develop de-novo after OLTx and may significantly influence the risk
      ratio for PSC recurrence in the liver graft. Key words: inflammatory bowel
      disease - primary sclerosing cholangitis - PSC-IBD.

PMID- 30223665
TI  - Possibilities of therapeutic manipulation of the gut microbiota.
AB  - Human gut microbiota, complex ecosystem of microbes associated with human gut, is
      essential for the development of the host's immune system and many other
      physiological functions. Recently, numerous diseases and syndromes were
      associated with disruption of this ecosystem thus stressing its importance in
      maintaining the host's health. Growing evidence suggests that by manipulating the
      gut microbiota, some of these diseases could be treated or even prevented. These
      manipulations include changes in diet, use of probiotics, prebiotics, antibiotics
      and fecal microbiota transplantation (FMT). The successes in FMT treatment of
      recurrent infection of Clostridium difficile led recently to a great interest in
      extending this treatment modality to other diseases with proven disruption of gut
      microbiota, such as ulcerative colitis or metabolic syndrome. Key words:
      Clostridium difficile - dysbiosis - fecal microbial transplantation - microbiota 
      prebiotics - probiotics.

PMID- 30223666
TI  - Prokinetics and their use in gastroenterology.
AB  - Gastrointestinal motility disorders are reflected in clinical medicine not only
      in the form of functional disorders but also as primary organic units or
      secondary manifestations of other diseases and physicochemical effects. Recent
      sophisticated diagnostic methods and basic research in the field of digestive
      tract motility have shown significant development. However, causal treatment of
      prokinetic motility disorders is still marginalized. A number of new effective
      drugs have been withdrawn from the market due to their significant side effects.
      The efficacy of others is limited to individual parts of the gastrointestinal
      tract (GIT), e.g. only the stomach or the intestine. The article presents an
      overview of prokinetic indications with an effect on selected pathological
      conditions. In addition to isolated administering of prokinetics, they can also
      be used in combination with other drugs, for example in the treatment of
      gastroesophageal reflux disease with proton pump inhibitors. There is currently
      no "gold standard" prokinetic, which would globally therapeutically and, at the
      same time, causally affect such a complicated pathophysiological chain of GIT
      dysmotility. There is ongoing research to develop new drugs with a beneficial
      effect on the propulsion activity disorder which, while maintaining a prokinetic
      effect over the full length of the GIT, would not show any adverse or side
      effects. Patient access in this case needs to be individualized according to the
      proven type of motility disorder. Key words: gastroesophageal reflux disease -
      gastrointestinal dysmotility - gastroparesis - intestinal pseudo-obstruction -
      obstipation.

PMID- 30223667
TI  - Colorectal cancer screening.
AB  - In developed countries, colorectal cancer represents one of the most common
      malignancy. Screening of colorectal cancer, as a tool of secondary prevention,
      lead to reduction of the incidence and mortality of this disease. It allows to
      capture not only the precancerous lesions, but also the earlier stages of
      colorectal cancer, which can be effectively treated. In the Czech Republic the
      National colorectal cancer screening program was launched in 2000. It is focused
      to asymptomatic individuals over 50 years old, who have a negative personal and
      family history of colorectal neoplasia. The basic tools of colorectal cancer
      screening in the Czech Republic include fecal occult blood test and colonoscopy.
      Introduction a population based screening program by addressed invitation in 2014
      led to increase the participation of the target population for screening. Key
      words: address invitation - colorectal cancer - epidemiology - population based
      screening - screening tests.

PMID- 30223668
TI  - Therapeutic digestive endoscopy I.
AB  - Digestive endoscopy today is able to examine the whole gastrointestinal tract. On
      the basis of the originally purely diagnostic procedures a range of therapeutic
      modalities has been developed over years, which in some indications have taken
      the place of surgical procedures and methods of invasive radiology. Of greatest
      importance are the methods of endoscopic resection and ablation designed for the
      treatment of early neoplasms of the digestive tract not accompanied by a
      significant risk of lymphatic and systemic dissemination. Resection methods
      include endoscopic polypectomy, endoscopic mucosal resection, endoscopic
      submucosal dissection and endoscopic transmural resection. Regarding ablation
      methods, commonly used in clinical practice are radiofrequency ablations in the
      treatment of dysplasia in Barrett's esophagus and argon plasma coagulation used
      in the treatment of symptomatic vascular malformations and small local residual
      neoplasms. Key words: digestive endoscopy - endoscopic ablation - endoscopic
      mucosal resection - endoscopic polyp-ectomy - endoscopic resection - endoscopic
      submucosal dissection - endoscopic transmural resection.

PMID- 30223669
TI  - Therapeutic digestive endoscopy II.
AB  - Digestive endoscopy today is able to examine the whole gastrointestinal tract. On
      the basis of the originally purely diagnostic procedures a range of therapeutic
      modalities was developed over years, which in some indications have taken the
      place of surgical procedures and methods of invasive radiology. Apart from the
      methods of endoscopic resection of early neoplasms of the digestive tract,
      digestive endoscopy plays an important role in diagnosing and treatment of
      bleeding and stenoses of the gastrointestinal tract. Plastic or self-expansible
      metal stents are introduced in the treatment of stenoses. Endoscopic retrograde
      cholangiopancreatography is a combined procedure capable of probing and
      intervening in the bile ducts and pancreatic duct under skiascopic control. Their
      direct visualization is possible with the method of oral cholangiopancreatoscopy.
      Endosonography-guided drainage and subsequent endoscopic necrectomy have become
      mini-invasive alternatives in the treatment of peripancreatic fluid collections.
      Key words: digestive endoscopy - endoscopic dilatation - endoscopic hemostasis -
      endoscopic retrograde chol-angiopancreatography - endosonography -
      cholangiopancreatography - stents.

PMID- 30223670
TI  - Long-Term Strategy for Assessing Carbonaceous Particulate Matter Concentrations
      from Multiple Fourier Transform Infrared (FT-IR) Instruments: Influence of
      Spectral Dissimilarities on Multivariate Calibration Performance.
AB  - Matching the spectral response between multiple spectrometers is a mandatory
      procedure when developing robust calibrations whose prediction is independent of
      instrument-related signal variations. A viable alternative to complex calibration
      transfer methods consists of matching the instrument spectral response by
      controlling a set of key instrumental and environmental parameters. This paper
      discusses the applicability of such an approach to three Fourier transform
      infrared (FT-IR) spectrometers used for the routine assessment of carbonaceous
      particulate matter concentrations in the Interagency Monitoring of PROtected
      Visual Environments (IMPROVE) speciation network. The effectiveness of the
      proposed matching procedure is evaluated by comparing the spectral response for
      each individual instrument in order to characterize the extent, and nature, of
      the remaining inter-instrument spectral dissimilarities. Instrument-related
      contributions to the signal were determined to be small compared with the
      spectral variability induced by the filter type used for sample collection. The
      impact of spectral differences on prediction was addressed through the comparison
      of model performance derived from multiple calibration scenarios. A hybrid model
      yielding accurate and homogeneous prediction regardless of the instrument was
      proposed for organic carbon (OC) and elemental carbon (EC), two major
      constituents of atmospheric particulate matter. Coefficients of determination of
      0.98 (OC) and 0.90 (EC) with median biases not exceeding 0.20 ug (OC) and 0.07 ug
      (EC) are reported. The long-term stability, assessed from weekly measurements of
      reference samples, shows a deviation in predicted concentrations of less than +/
      5% over a 2.5-year period for most of the data collected. Extending OC and EC
      hybrid models to the prediction of ambient samples collected during the two
      subsequent years provides satisfactory performance. The proposed instrument
      matching procedure coupled with the relative simplicity of the hybrid model is an
      alternative to computationally advanced calibration transfer methodologies for
      the characterization of carbonaceous particulate matter using multiple FT-IR
      instruments.

PMID- 30223672
TI  - The Canadian health system's "administrative efficiency" is a problem.
AB  - The Commonwealth Fund's "administrative efficiency" criterion ranks Canada poorly
      sixth of the 11 countries compared. On two of the four patient-sourced measure
      used in this criterion, Canada was below the international average performance.
      For two of the three physician-sourced measures, Canada performs well but is
      significantly behind the best performing country. This suggests that Canada has
      room to improve, despite being better than average. Two opportunities for health
      leaders to make improvements are in relation to reducing the time physicians
      spend negotiating patient access to needed medications and reducing other
      administrative burdens related to claiming.

PMID- 30223671
TI  - Does health system performance reporting stimulate change?
AB  - For numerous countries, including Canada, regular health system performance
      reporting has become increasingly routine if not mandated by legislation. In
      Canada, the health system performance reporting agenda includes multiple players
      at all levels from national organizations to provincial health (quality) councils
      and others. Canada, like many other countries, also participates in international
      health system performance reporting initiatives. Making sense of what all of
      these reporting initiatives are telling us about health system performance both
      within Canada and compared to other countries is becoming increasingly more
      challenging. For almost 20 years, the Canadian Institute for Health Information
      has worked with provinces, territories, and other key partners to develop
      comparable, standardized pan-Canadian performance indicators. Throughout this
      process, many lessons have been identified including the actionability one can
      reasonably expect from public reporting initiatives. This article outlines some
      of the key aspects of these lessons.

PMID- 30223673
TI  - A Systematic Review of Genetic Influence on Psychological Resilience.
AB  - When exposed to adversity, some individuals are at an increased risk of
      posttraumatic stress disorder, experiencing persistent biopsychosocial
      disturbances, whereas others adapt well, described as resilience. Resilience is a
      complex biopsychosocial phenomenon conceptualized as adaptation to adversity
      influenced by an individual's genetic variants, epistasis, epigenetics, and gene
      by-environment interactions. Studies on psychological resilience have focused on
      behavioral and psychosocial variables with far less examination of the genetic
      contributions. The purpose of this review is to identify specific genetic
      variants contributing to the biological capacity for psychological resilience.
      PubMed and PsycINFO were searched using the following key words: psychological
      resilience AND genotype(s). Additional articles were identified from the Human
      Genome Epidemiology Navigator using the term resilience, psychological. Ten
      studies met the criteria. Six genes were empirically associated with
      psychological resilience: serotonin-transporter-linked polymorphic region ( 5
      HTTLPR), dopamine receptor D4, brain-derived neurotrophic factor ( BDNF),
      corticotropin-releasing hormone receptor 1, oxytocin receptor and regulator of G
      protein signaling 2 . The findings of this systematic review suggest that the L/L
      or L'/L' genotype of 5-HTTLPR and rs25531 in children/adolescents and the S/S or
      S'/S' genotype in adults are most frequently related to resilience. Additionally,
      the Val/Val genotype of rs6265 in BDNF in Caucasians was also associated with
      resilience. There are numerous factors contributing to the complexity of
      determining the genetic influence on resilience including analysis of rs25531,
      assumptions of the mode of inheritance, operationalization of resilience,
      demographic and population characteristics, sample size, and other types of
      genetic influence including epistasis and epigenetics. While current evidence is
      supportive, further investigation of the genetic influence on resilience is
      required.

PMID- 30223674
TI  - Income inequality, structural racism, and Canada's low performance in health
      equity.
AB  - In 2017, the Commonwealth Fund released a report evaluating 11 countries'
      healthcare systems on a variety of domains; one of these domains was health
      equity. Canada's score on health equity placed it among the bottom three
      countries. This article applies a conceptual framework for health equity
      developed by the World Health Organization's Commission on the Social
      Determinants of Health to reflect upon and discuss mechanisms that may help to
      explain Canada's low score. We discuss the role that two societal-level
      constructs-income inequality and structural racism-play in shaping population
      health and health equity. We use publically available data to examine whether
      income inequality correlates with the Commonwealth Fund report's equity measures.
      We also comment on the role that Canada's history of colonialism may play in its
      health equity ranking.

PMID- 30223676
TI  - Connecting patient experience, leadership, and the importance of involvement,
      information, and empathy in the care process.
AB  - To improve health outcomes, restore trust, and create a safe and healing
      environment for patients, the health system needs to shift from being disease,
      system, and provider focused to being patient centred. Drawing from a patient
      story, this article focuses on three aspects of the care process that have a
      significant impact on patient experience: involvement in care, information about
      treatment and care, and empathy and respect. It will also provide recommendations
      for leaders in how to become more patient centred and aligned to the LEADS
      competency framework.

PMID- 30223675
TI  - Patient Satisfaction Is Associated With Dialysis Facility Quality and Star
      Ratings.
AB  - The Dialysis Facility Compare Star Rating and the Quality Incentive Program (QIP)
      generate separate performance scores from clinical measures, and the In-Center
      Hemodialysis Consumer Assessment of Healthcare Providers and Systems (ICH-CAHPS)
      survey evaluates patient satisfaction across 6 separate domains related to
      nephrologists, dialysis facility, and information transmission. This study
      examined the relationship of the 3 measures for US clinics, modeling the 6 ICH
      CAHPS domains as independent variables and QIP and star ratings as dependent
      variables. Among 3176 dialysis clinics, domains assessing dialysis facility and
      information transmission had a consistently stronger relationship with QIP and
      star ratings than the domains assessing nephrologists: QIP, beta (95% CI) = 1.62
      (1.26-1.97) for dialysis facility staff rating, 0.70 (0.35-1.05) for
      nephrologists; star rating, odds ratio (95% CI) = 1.38 (1.29-1.49) for dialysis
      facility staff rating, 1.17 (1.09-1.25) for nephrologists. Patient satisfaction
      is associated with dialysis care quality, with surprising differences between
      nephrologists and dialysis facilities.

PMID- 30223677
TI  - The Importance of Using Multiple Data Sources in Policy Assessments: Lessons From
      Two Conditional Cash Transfer Programs in New York City.
AB  - BACKGROUND: The high costs of implementing surveys are increasingly leading
      research teams to either cut back on surveys or to rely on administrative
      records. Yet no policy should be based on a single set of estimates, and every
      approach has its weaknesses. A mixture of approaches, each with its own biases,
      should provide the analyst with a better understanding of the underlying
      phenomenon. This claim is illustrated with a comparison of employment effect
      estimates of two conditional cash transfer programs in New York City using survey
      and administrative unemployment insurance (UI) data. OBJECTIVES: This article
      explores whether using administrative data and survey data produce different
      impact estimates and investigates the source of differential effects between data
      sources. RESEARCH DESIGN: The results of a survey nonresponse bias analysis and
      an analysis of characteristics of non-UI-covered job characteristics using data
      collected on 6,000 families who enrolled in either the Family Rewards or Work
      Rewards evaluation are presented. RESULTS: In both evaluations, survey data
      showed positive employment effects, while administrative data showed no
      statistically significant employment effects. Family Rewards increased employment
      mostly in non-UI-covered jobs, while the positive survey impact estimates in Work
      Rewards were partially due to survey nonresponse bias. CONCLUSIONS: Despite cost
      pressures leading researchers to collect and analyze only administrative records,
      the results suggest that survey and administrative records data both suffer from
      different kinds of sample attrition, and researchers may need to triangulate data
      sources to draw accurate conclusions about program effects. Developing more
      economical data collection practices is a major priority.

PMID- 30223679
TI  - Conscious Perception of Facial Asymmetry in a Unilateral Cleft Lip Model: Body
      Dysmorphic Disorder Is an Exclusion Criterion.

PMID- 30223678
TI  - How do we know what we don't know? Exploring Deaf people's experiences of
      supporting their Deaf family member living with dementia.
AB  - Deaf sign language users living with dementia and their carers, some of whom are
      Deaf, routinely face everyday barriers in accessing information, support (both
      formal and informal) and services. The familial care situation is further
      complicated given that most Deaf people will choose a life partner who is Deaf
      and most Deaf couples will have hearing children. This study focussed
      specifically on the everyday experiences of Deaf carers and the impact of caring
      for a loved one with dementia. Drawing on data from a wider consultation about
      dementia care, three Deaf carers were directly interviewed in British Sign
      Language by a Deaf researcher about their everyday experiences of care, support,
      and services. Thematic analysis focussed on: access is more than the provision of
      interpreters; effective care for the carers; and unknowing risk taking. Findings
      demonstrate the multifaceted effects of barriers to knowledge and information
      when the care partner is also Deaf, the urgent need for effective support for
      Deaf carers and unrecognised safeguarding concerns that are a result of lack of
      access to forms of basic knowledge about living with someone with dementia and
      potential coping strategies. Nonetheless, the participants demonstrated novel
      solutions and resilience in the face of these multiple challenges. Implications
      are drawn for future targeted services to supported Deaf carers of people
      affected by dementia.

PMID- 30223680
TI  - Cleft Care: Intraoral 3D Scanning.

PMID- 30223681
TI  - Changes in duodenal CD163-positive cells in dogs with chronic enteropathy after
      successful treatment.
AB  - Chronic enteropathy (CE) in dogs is characterized retrospectively per treatment
      response as food-responsive enteropathy (FRE), antibiotic-responsive enteropathy
      (ARE), and immunosuppressant-responsive enteropathy (IRE) - the latter most
      resembling inflammatory bowel disease in people. The aim of this study was to
      characterize duodenal macrophages (Mphi) in CE using immunohistochemistry; with
      calprotectin (CAL) as a marker of early differentiated Mphi and CD163 expression
      as a marker for resident Mphi in the duodenum before and after treatment. Prior
      to treatment, dogs with FRE and IRE had a lower CD163+/CAL+ ratio than control
      dogs (CTRL) in crypts; this increased significantly and normalized compared with
      CTRL after treatment. Conversely, the CD163+/CAL+ ratio in dogs with ARE was
      comparable to that in healthy dogs before and after treatment. In summary, these
      results suggest that Mphi play a role in the pathogenesis of CE in FRE and IRE,
      with a decrease in resident Mphi and an increase in early differentiated Mphi,
      but not in ARE dogs. Mphi normalize after successful treatment.

PMID- 30223682
TI  - Mass Spectrometry and Proteomics 2018: the Mass Spectrometry Society of Japan,
      Japanese Proteomics Society, and Asia-Oceania Human Proteome Organization.
AB  - INTRODUCTION: The mass spectrometry society of Japan, Japanese proteomics
      society, and Asia-Oceania human proteome organization held the conference 'Mass
      Spectrometry and Proteomics 2018' in Osaka, Japan, on May 15-18, 2018. This
      international conference focused on cutting edge technologies and their
      applications in a variety of research fields such as agriculture, material
      science, environmental factors, and clinical applications. An overview of the
      conference and a summary of the major lectures are reported here. Expert
      commentary: The meeting will facilitate the development of fundamental
      technologies and the multi-disciplinary applications of proteomics.

PMID- 30223683
TI  - Interviewing older people about their experiences of emergency hospital
      admission: methodology in health services research.
AB  - This essay makes the case for increased use of patient-centred methodologies,
      which involve patients and the public, in the area of emergency admissions
      research in the United Kingdom. Emergency admission research has rarely made use
      of the patient voice when attempting to find a rate of 'inappropriate' admission
      for older people, instead focusing on professional viewpoints and more abstract
      tools. We argue for the important insights that patients and their families bring
      to emergency admissions research and for the need to listen to and use these
      voices to find more holistic responses to the issue of unplanned admissions to
      hospital for those aged over 65. This area of health services research is highly
      complex, but without involving the patient viewpoint we risk not understanding
      the full story of events leading up to admission and what preventative measures
      might have helped, and therefore we also risk developing less effective,
      simplistic solutions. In the face of increasing challenges to the National Health
      Service's ability to provide safe, effective and affordable care for older
      people, researchers need to listen to those with direct and longitudinal
      experience of their ill health and admission.

PMID- 30223684
TI  - Paper spray ionization mass spectrometry: recent advances and clinical
      applications.
AB  - INTRODUCTION: Paper spray mass spectrometry has provided a rapid, quantitative
      ambient ionization method for xenobiotic and biomolecule analysis. As an
      alternative to traditional sample preparation and chromatography, paper spray
      demonstrates the sampling ionization of a wide range of molecules and significant
      sensitivity from complex biofluids. The amenability of paper spray with dried
      blood spots and other sampling types shows strong potential for rapid, point-of
      care (POC) analysis without time-consuming separation procedures. Areas covered:
      This special report summarizes the current state and advances in paper spray mass
      spectrometry that relate to its applicability for clinical analysis. It also
      provides our perspectives on the future development of paper spray mass
      spectrometry and its potential roles in clinical settings. Expert commentary:
      Paper spray has provided the fundamental aspects of ambient ionization needed for
      implementation at the POC. With further clinical management and standardization,
      paper spray has the potential to replace traditional complex analysis procedure
      for rapid quantitative detection of illicit drugs, therapeutic drugs and
      metabolites. Surface and substrate modifications also offer significant
      improvement in desorption and ionization efficiencies, resulting in enhanced
      sensitivity. Comprehensive analysis of metabolites and lipids will further extend
      the implementation of paper spray ionization mass spectrometry into clinical
      applications.

PMID- 30223685
TI  - Compression screws and buttress plate versus compression screws only for Hoffa
      fracture in Chinese patients: a comparative study.
AB  - Objective To compare compression screws and buttress plate (CS plus BP) with
      compression screws only (CS) in treating patients with Hoffa fracture. Methods
      This retrospective study included Chinese patients with Hoffa fracture treated by
      open reduction and internal fixation. Radiographs and clinical outcomes (range of
      movement [ROM], bone union and Knee Society Score [KSS]) were compared between
      patients treated using CS plus BP versus CS only. Results At 4 months following
      surgery, significantly better outcomes were shown in the CS plus BP group ( n =
      24) versus CS only group ( n = 21) regarding ROM (120.4 +/- 5.2 degrees  versus
      110 +/- 7.1 degrees ) and KSS (85.5 +/- 4.1 versus 79.7 +/- 3.3). At the 12-month
      follow-up, significantly better outcomes were maintained in the CS plus BP versus
      CS only group regarding ROM (126.2 +/- 7.4 degrees  versus 120.5 +/- 8.2 degrees
      ) and KSS (88.3 +/- 4.6 versus 84.2 +/- 4.0). At the final follow-up, all
      patients had normal fracture healing and no malunion, nonunion or reduction loss.
      Conclusions Fixation with CS plus BP for Hoffa fracture is effective and
      reliable, and may provide more adequate stability and better outcomes versus CS
      only.

PMID- 30223686
TI  - Initial experience with precipitating hydrophobic injectable liquid in cerebral
      arteriovenous malformations.
AB  - Background Precipitating hydrophobic injectable liquid is a newly introduced
      liquid embolic agent for endovascular embolization with some technical advantages
      over other liquid embolic agents. We present our initial experience with
      precipitating hydrophobic injectable liquid in the endovascular treatment of
      cerebral arteriovenous malformations. Methods From October 2015 to January 2018,
      27 patients harboring cerebral arteriovenous malformations underwent endovascular
      embolization with precipitating hydrophobic injectable liquid 25. Clinical
      features, angiographic results, procedural details, complications, and follow-up
      details were retrospectively analyzed. Results Twenty-seven patients with
      cerebral arteriovenous malformations were included. Total obliteration in one
      endovascular session was confirmed for 14/27 (52%) patients. Partial embolization
      was attained in 13 patients (48%) in whom staged treatment with following
      radiosurgery or surgery was planned. No mortality was recorded in this series.
      Complications during or after the embolization occurred in six of 27 (22.2%)
      patients. Conclusion In our initial experience, precipitating hydrophobic
      injectable liquid has acceptable clinical outcome comparable to other liquid
      embolic agents. Although this is the largest reported study in arteriovenous
      malformation treatment with precipitating hydrophobic injectable liquid, further
      studies are needed to validate its safety and efficacy.

PMID- 30223687
TI  - Proteomics and the microbiome: pitfalls and potential.
AB  - INTRODUCTION: Human symbiotic microbiota are now known to play important roles in
      human health and disease. Significant progress in our understanding of the human
      microbiome has been driven by recent technological advances in the fields of
      genomics, transcriptomics, and proteomics. As a complementary method to
      metagenomics, proteomics is enabling detailed protein profiling of the microbiome
      to decipher its structure and function and to analyze its relationship with the
      human body. Fecal proteomics is being increasingly applied to discover and
      validate potential health and disease biomarkers, and Therapeutic Goods
      Administration (TGA)-approved instrumentation and a range of clinical assays are
      being developed that will collectively play key roles in advancing personalized
      medicine. Areas covered: This review will introduce the complexity of the
      microbiome and its role in health and disease (in particular the gastrointestinal
      tract or gut microbiome), discuss current genomic and proteomic methods for
      studying this system, including the discovery of potential biomarkers, and
      outline the development of clinically accepted protocols leading to personalized
      medicine. Expert commentary: Recognition of the important role the microbiome
      plays in both health and disease is driving current research in this key area. A
      proteogenomics approach will be essential to unravel the biologies underlying
      this complex network.

PMID- 30223688
TI  - Targeting IL-23 in Crohn's disease.
AB  - INTRODUCTION: Interleukin (IL)-23, a cytokine produced by antigen presenting
      cells, targets both T cells and non-T cell types with the downstream effect of
      enhancing inflammatory pathways. Genome-wide association studies and data from
      human and mouse models of intestinal inflammation support the pathogenic role of
      IL-23 in Crohn's disease (CD), an immune-mediated disorder that can involve any
      part of the gastrointestinal tract. Areas covered: This review summarizes the
      available data on the role of IL-23 in CD and discusses the therapeutic relevance
      of blocking the function of IL-23 in this disorder. Expert commentary: The use of
      biologic drugs, such as anti-TNF and anti-integrins, has largely improved the
      management of CD patients. However, a significant proportion of CD patients
      taking these drugs continue to experience symptoms and have inflammation in the
      gut, thus suggesting a need for new agents, which block other inflammatory
      signals. Data emerging from trials with IL-23p40 and p19 blockers indicate that
      IL-23 is a valid therapeutic target. More studies are needed to optimize the
      therapeutic regimens, ascertain whether selective inhibition of IL-23p19 is more
      advantageous than blockade of p40, a subunit shared by IL-12 and IL-23, and
      evaluate the long-term risk of these approaches.

PMID- 30223689
TI  - Heart rate reduction after ivabradine might be associated with reverse electrical
      remodeling in patients with cardiomyopathy and left bundle branch block.
AB  - Left bundle branch block increases the risk of death in patients with chronic
      heart failure. We herein report four clinical cases of patients with chronic
      heart failure caused by nonischemic cardiomyopathy with left bundle branch block
      that occurred when adding ivabradine to optimal medical therapy, resulting in
      reverse electrical and mechanical remodeling. This phenomenon might be explained
      by the effect of ivabradine on reverse remodeling of the left ventricle with
      improvement of intraventricular conduction.

PMID- 30223690
TI  - Gender differences on benefits and risks associated with oral antithrombotic
      medications for coronary artery disease.
AB  - INTRODUCTION: Despite the significant advances in the pharmacological and
      interventional management of patients with cardiovascular disease (CVD) over the
      last decades, cardiovascular mortality remains the leading cause of death. Large
      randomized clinical trials have investigated the efficacy and safety of different
      antithrombotic medications in patients with CVD. Although female gender is
      generally underrepresented in these clinical trials, most analyses clearly
      indicate that both men and women may accrue therapeutic benefits from
      antithrombotic management strategies. Areas covered: This review aims to provide
      a comprehensive and focused update on gender-related comparative clinical studies
      of antithrombotic therapies in patients suffering from CVD. Expert opinion:
      Current evidence supports the understanding of a similar therapeutic effect
      between genders with signals of an increased risk of bleeding in women. However,
      important gaps in evidence exist due to the overall limited percentage of women
      that have been enrolled in randomized controlled trials. A greater awareness of
      gender-related issues in antithrombotic therapy should be promoted among
      physicians and further evidence from large clinical trials looking at the safety
      and efficacy balance of different antithrombotic strategies in women is
      warranted.

PMID- 30223691
TI  - Rollercoaster ride of kynurenines: steering the wheel towards neuroprotection in
      Alzheimer's disease.
AB  - INTRODUCTION: Alzheimer's disease (AD) is associated with cerebral cognitive
      deficits exhibiting two cardinal hallmarks: accruement of extracellular amyloid
      plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated
      tau protein. The currently accessible therapeutic armamentarium merely provides
      symptomatic relief. Therefore, the cry for prospective neuroprotective strategies
      seems to be the need of the hour. Areas covered: This review comprehensively
      establishes correlation between kynurenine pathway (KP) metabolites and AD with
      major emphasis on its two functionally contrasting neuroactive metabolites i.e.
      kynurenic acid (KYNA) and quinolinic acid (QUIN) and enlists various clinical
      studies which hold a potential for future therapeutics in AD. Also, major
      hypotheses of AD and mechanisms underlying them have been scrutinized with the
      aim to brush up the readers with basic pathology of AD. Expert opinion: KP is
      unique in itself as it holds two completely different domains i.e. neurotoxic
      QUIN and neuroprotective KYNA and disrupted equilibrium between the two has a
      hand in neurodegeneration. KYNA has long been demonstrated to be neuroprotective
      but lately being disparaged for cognitive side effects. But we blaze a trail by
      amalgamating the pharmacological mechanistic studies of KYNA in kinship with
      alpha7nAChRs, NMDARs and GABA which lends aid in favour of KA.

PMID- 30223692
TI  - The  early  preclinical and clinical development of ganaplacide (KAF156), a novel
      antimalarial compound.
AB  - INTRODUCTION: Ganaplacide (previously known as KAF156) is a novel antimalarial
      compound part of the imidazolopiperazine family. Areas covered: At the time of
      writing, a total of eight studies addressing its preclinical and clinical
      development have been published on this compound, which is currently in phase 2
      of clinical development, alongside lumefantrine in a novel soluble formulation as
      combination partner. This review provides an overview and interpretation of the
      published pre-clinical and clinical data of this possible next-generation
      antimalarial drug. Expert opinion: In the search for a 'magic bullet' in malaria
      therapy and prophylaxis facilitating single encounter radical cure and
      prophylaxis, ganaplacide demonstrates some promising properties toward this
      ultimate goal. The available data suggest that ganaplacide exerts multi-stage
      antimalarial activity, and that its pharmacokinetic profile potentially allows
      for a simplified dosing regimen compared to that of existing antimalarial drug
      combinations. The first in-patient results demonstrate promising single-dose
      antimalarial activity, and no serious in-human safety and tolerability concerns
      have been reported to date.

PMID- 30223693
TI  - Ertugliflozin as a monotherapy for the treatment of type 2 diabetes.
AB  - INTRODUCTION: Sodium-dependent glucose transporter 2 (SGLT2) inhibitors are
      novel, potent oral anti-diabetic agents in a beta-cell function-independent
      manner, inhibiting SGLT2-mediated renal glucose reabsorption and thus increasing
      urinary glucose excretion. Ertugliflozin (SteglatroTM) is a new oral SGLT2
      inhibitor for the treatment of patients with type 2 diabetes mellitus (T2DM) as a
      monotherapy or in combination with other anti-diabetic agents. Areas covered:
      This review summarizes the collected data concerning the pharmacokinetics,
      clinical efficacy, as well as safety and tolerability profiles of ertugliflozin
      given as a monotherapy for the management of T2DM. Expert opinion: Good glycemic
      control is crucial to the management of T2DM, and accordingly, anti-diabetic
      agents with various anti-hyperglycemic mechanisms are developed one after
      another. Based on the available clinical trials of ertugliflozin as a monotherapy
      for T2DM, it could be found that ertugliflozin effectively improves the glycemic
      control, body weight and blood pressure of patients with a low risk of
      hypoglycemia. It is also found that ertugliflozin moderately reduces their blood
      pressure, which is beneficial for decreasing the risk of cardiovascular disease.
      These attributes show the good potential of ertugliflozin as an adjunct treatment
      to diet and exercise for improving glycemic control in patients with T2DM.

PMID- 30223694
TI  - Recurrent ovarian cancer 8 months after induction and bevacizumab consolidation:
      rationale for using trabectedin + pegylated liposomal doxorubicin in second line.
AB  - OBJECTIVES: Ovarian cancer patients with relapse 6-12 months after last platinum
      treatment, who have received bevacizumab consolidation and are not BRCA mutant,
      represent a considerable therapeutic challenge. METHODS: By means of illustrative
      case study, this review evaluates various treatment strategies for use at first
      relapse in an ovarian cancer patient with limited sensitivity to platinum.
      RESULTS: Clinical parameters predictive of complete resection in secondary
      cytoreductive surgery include an Eastern Cooperative Oncology Group performance
      status of 0, no residual disease after first surgery, and <500 mL of ascites.
      Options for systemic therapy include platinum-based therapies, non-platinum
      combinations, and non-platinum single agents. The patient's circumstances
      suggested that the non-platinum combination of trabectedin + pegylated liposomal
      doxorubicin (PLD) would be most appropriate. Trabectedin + PLD may enhance
      response to the next platinum cycle and thus prolong survival although this
      hypothesis requires confirmation. At minimum, trabectedin + PLD provides
      additional time for patients to recover from previous platinum toxicity while
      receiving an effective treatment. CONCLUSION: In recurrent ovarian cancer
      patients with expected suboptimal response to platinum, trabectedin + PLD may
      offer an active alternative, which differs from the first-line schedule, and may
      enhance the efficacy of subsequent platinum rechallenge.

PMID- 30223695
TI  - Management of relapsed ovarian cancer in routine clinical practice: a case study.
AB  - OBJECTIVE: In patients with recurrent ovarian cancer, there are certain
      situations where further surgery and/or next-line platinum-based chemotherapy is
      not feasible or is not the best option. Multidisciplinary teams have a key role
      in reviewing available options and selecting the most appropriate intervention.
      METHODS: A case study of relapsed ovarian cancer illustrates some of the factors
      that shape decision-making and shows the potential of a non-platinum-based
      regimen in the context of limited platinum sensitivity. RESULTS: Taking into
      account the patient's individual circumstances, many options were discarded by
      the tumor board. Further surgery was not recommended as initial surgery had been
      suboptimal. Platinum-based regimens incorporating bevacizumab were not indicated
      due to exposure to bevacizumab in the first-line setting. Other platinum-based
      regimens were not recommended in general, due to limited platinum sensitivity
      (relapse <12 months after previous platinum) and unacceptable toxicity. A
      decision was taken to treat with trabectedin + pegylated liposomal doxorubicin
      (PLD), which provided 15 months of disease control. Subsequent platinum
      rechallenge led to a complete response. CONCLUSION: Second-line use of
      trabectedin + PLD in patients with limited platinum sensitivity may restore
      sensitivity at next platinum.

PMID- 30223696
TI  - Foreword.

PMID- 30223697
TI  - Trabectedin + pegylated liposomal doxorubicin in third-line treatment of platinum
      sensitive relapsed ovarian cancer: a case study.
AB  - BACKGROUND: The challenges of managing relapsed ovarian cancer increase as more
      advanced lines of chemotherapy are achieved. METHODS: A case study is presented
      to illustrate the complexities of selecting treatment in a patient with platinum
      sensitive relapsed ovarian cancer and exposure to two previous lines of platinum
      based chemotherapy. RESULTS: In this clinical scenario, options include re
      treatment with platinum-based chemotherapy or treatment with a nonplatinum single
      agent or a nonplatinum combination. In this case, the nonplatinum combination of
      trabectedin + pegylated liposomal doxorubicin (PLD) was selected as the patient
      had limited platinum sensitivity (progression-free interval of 9 months), no BRCA
      mutation, and taking into account evidence that the regimen is effective and safe
      in the third line and beyond and may restore platinum sensitivity. After nine
      cycles of trabectedin + PLD, there was no evidence of disease. The patient was
      able to resume normal activities during therapy. Progression-free interval (PFI)
      was 17 months before disease progression. Subsequent platinum rechallenge
      produced a partial response. CONCLUSION: Trabectedin + PLD may be an option for
      patients with platinum-sensitive relapsed ovarian cancer, including those who
      have received two or more previous lines of platinum.

PMID- 30223698
TI  - Patient-reported outcomes in ovarian cancer: are they key factors for decision
      making?
AB  - INTRODUCTION: Patient-reported outcomes (PROs), including quality-of-life
      considerations, are increasingly becoming key factors in clinical decision
      making. Areas covered: This review provides an overview of the current status of
      PROs in guiding clinical trial design and clinical decision making in patients
      with ovarian cancer and previews the future potential of PROs in these settings.
      Expert commentary: In ovarian cancer, considerable discord exists between
      patients and physicians regarding perceived symptom burden. During maintenance
      therapy, it is important that the most appropriate PROs (i.e. endpoints and
      respective measuring tools) are selected to evaluate patients. Research continues
      into identifying PROs most likely to facilitate and enhance reporting of
      symptoms, adverse events, and subjective benefit. Some recent studies performed
      in ovarian cancer, such as the SOLO2/ENGOT-Ov21 and AURELIA trials, have reported
      valuable PRO data pertaining to the Trial Outcome Index (TOI) score, quality
      adjusted progression-free survival (QAPFS), and time without symptoms and
      toxicity (TWiST). In future, PROs are likely to become increasingly important in
      clinical trial design, regulatory procedures, and provision of valuable
      prognostic information to patients and physicians in clinical practice.

PMID- 30223699
TI  - Triphalangeal thumb: clinical features and treatment.
AB  - Triphalangeal thumb is a rare congenital anomaly in which the thumb has three
      phalanges. Clinical presentation of triphalangeal thumb can vary considerably and
      can be present in both hands or unilateral. The thumb can be long with a finger
      like appearance. The presence of clinodactyly depends on the shape of the extra
      phalanx varying from wedge-shaped to rectangular. Various joints, ligaments,
      muscles, and tendons of the first ray can be hypoplastic or absent, with varying
      degrees of stiffness or instability. The aim of surgical treatment is to
      reconstruct or correct the anatomic anomalies to obtain greater function and a
      more acceptable appearance. In our series, operations varied from removal of the
      delta phalanx with ligament reconstruction to multiple osteotomies and
      rebalancing of soft tissues. Results in these often complex cases can be
      rewarding if the surgeon has sufficient knowledge of the underlying anatomic
      differences. This review summarizes our current concepts of presentation and
      management of the triphalangeal thumb.

PMID- 30223700
TI  - Salvage extracorporeal membrane oxygenation in induction-associated acute
      respiratory distress syndrome in acute leukemia patients: A case series.
AB  - BACKGROUND: The prognosis of hematologic malignancies has improved over the past
      three decades. However, the prognosis in hematologic malignancies with severe
      acute respiratory distress syndrome has remained poor. Initial reports regarding
      the utility of extracorporeal membrane oxygenation in hematologic malignancies
      have been controversial, with limited evaluations of acute leukemia patients
      supported by extracorporeal membrane oxygenation. METHODS: We conducted a
      retrospective review of patients with acute leukemia who developed acute
      respiratory distress syndrome requiring veno-venous extracorporeal membrane
      oxygenation support at our facility from July 2015 through August 2017. RESULTS:
      Four cases of acute myelogenous leukemia with respiratory failure and acute
      respiratory distress syndrome treated with veno-venous extracorporeal membrane
      oxygenation while undergoing induction chemotherapy were identified. All patients
      completed induction therapy with addition of extracorporeal membrane oxygenation
      support, with two patients dying secondary to their acute leukemia and the other
      two surviving to allogeneic hematopoietic stem cell transplant. Overall, 75%
      (three of four) survived to decannulation with a 1-year survival rate following
      extracorporeal membrane oxygenation of 50% (two of four). CONCLUSION: Currently,
      the use of extracorporeal membrane oxygenation in patients with hematologic
      malignancies who develop severe acute respiratory distress syndrome remains
      controversial. Although extracorporeal membrane oxygenation in post-allogeneic
      hematopoietic stem cell transplant is associated with poorer outcomes, our data
      suggest that salvage extracorporeal membrane oxygenation support is a viable
      option to manage moderate to severe acute respiratory distress syndrome while
      completing therapeutic chemotherapy and following in the peri-induction phase of
      acute leukemia.

PMID- 30223701
TI  - Vocabulary as a Central Link between Phonological Working Memory and Narrative
      Competence: Evidence from Monolingual and Bilingual Four-Year-Olds from Different
      Socioeconomic Backgrounds.
AB  - Phonological working memory capacity, vocabulary size, and narrative competence
      are important skills in children's L1 and L2 acquisition, which may vary as a
      function of their language background and socioeconomic status (SES). We
      investigated test data of 56 typically developing 4-year-old kindergarten
      children from two SES and two language backgrounds: 29 children (15 higher SES,
      14 lower SES) were monolingual German-speaking, and 27 children (14 higher SES,
      13 lower SES) were successive Turkish-German bilinguals. The tests comprised a
      non-word repetition task testing phonological working memory, receptive
      vocabulary tests (in L1 and L2), and a narrative task. We investigated the
      effects of SES and language background on children's test performance. Results
      indicate that SES was a highly significant factor for phonological working memory
      and vocabulary in the monolingual children, but not in the bilingual children.
      Although the items of the non-word repetition task followed German phonotactic
      structure, lower SES (LSES) L2 children did not differ significantly from their
      monolingual LSES peers, demonstrating that there was no bilingual working memory
      disadvantage in the LSES group. A significant effect of language background was
      found for German vocabulary and for all categories of narrative competence, but
      only two slight SES effects on narrative competence. Significant correlations
      were found between phonological working memory and vocabulary as well as between
      vocabulary and narrative competence, but not between phonological working memory
      and narrative competence. Results suggest that phonological working memory and
      narrative competence are different domains of language awareness, and that
      vocabulary may act as the central variable mediating between them.

PMID- 30223702
TI  - Optimal drainage cannula position in dual cannulation for veno-venous
      extracorporeal membrane oxygenation.
AB  - INTRODUCTION:: Recently, the use of veno-venous extracorporeal membrane
      oxygenation for adult patients with severe acute respiratory failure has
      increased. We previously investigated the optimal return cannula position;
      however, the optimal drainage cannula position has not yet been fully clarified.
      The aim of this study was to investigate the optimal drainage cannula position.
      METHODS:: Veno-venous extracorporeal membrane oxygenation was performed in four
      adult goats (mean body weight 59.6 +/- 0.6 kg). The position of the drainage
      cannula was varied among the right atrium, the upper inferior vena cava, and the
      lower inferior vena cava, whereas the position of the return cannula was fixed in
      the superior vena cava. The recirculation fraction and arterial oxygen saturation
      and pressure (SaO2, PaO2) were measured in all drainage cannula positions.
      RESULTS:: In the lower inferior vena cava drainage cannula position, the
      recirculation fraction was the lowest. In the lower inferior vena cava, upper
      inferior vena cava, and right atrium drainage cannula positions at 3 L/min, SaO2
      and PaO2 after 20 min were 92.9% +/- 4.9% and 75.1 +/- 26.0 mm Hg, 99.5% +/- 0.5%
      and 113.8 +/- 20.9 mm Hg, and 93.8% +/- 6.2% and 91.9 +/- 17.7 mm Hg,
      respectively. CONCLUSION:: With respect to blood oxygenation, the optimal
      position for the drainage cannula was the upper inferior vena cava. These
      findings suggested that blood from the superior vena cava, inferior vena cava,
      and hepatic vein was most efficiently drained in the upper inferior vena cava
      cannula position.

PMID- 30223703
TI  - Angiotensin IV suppresses inflammation in the brains of rats with chronic
      cerebral hypoperfusion.
AB  - INTRODUCTION: This study aimed to evaluate the influence of central angiotensin
      IV (Ang IV) infusion on chronic cerebral hypoperfusion (CCH)-related
      neuropathological changes including amyloid-beta (Abeta), hyperphosphorylated tau
      (p-tau) and the inflammatory response. MATERIALS AND METHODS: Rats with CCH
      received central infusion of Ang IV, its receptor AT4R antagonist divalinal-Ang
      IV or artificial cerebrospinal fluid for six weeks. During this procedure, the
      systolic blood pressure (SBP) was monitored, and the levels of Abeta42, p-tau and
      pro-inflammatory cytokines in the brain were detected. RESULTS: Rats with CCH
      exhibited higher levels of Abeta42, p-tau and pro-inflammatory cytokines in the
      brain when compared with controls. Infusion of Ang IV significantly reduced the
      expression of pro-inflammatory cytokines in the brains of rats with CCH.
      Meanwhile, the reduction of pro-inflammatory cytokines levels caused by Ang IV
      was reversed by divalinal-Ang IV. During the treatment, the SBP in rats was not
      significantly altered. CONCLUSION: This study demonstrates for the first time
      that Ang IV dose-dependently suppresses inflammation through AT4R in the brains
      of rats with CCH, which is independent from SBP. These findings suggest that Ang
      IV/AT4R may represent a potential therapeutic target for CCH-related neurological
      diseases.

PMID- 30223705
TI  - Combined findings of FDG-PET and arterial spin labeling in sporadic Creutzfeldt
      Jakob disease.
AB  - Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal progressive
      neurodegenerative disease. Multimodal approaches, including electroencephalogram,
      diffusion-weighted imaging (DWI) of brain MRI, and cerebrospinal fluid
      biomarkers, have been applied to increase the diagnostic accuracy of sCJD.
      Although previous studies suggested DWI could be the most useful modality for
      sCJD diagnosis, whether metabolism changes underlying in sCJD are still poorly
      understood. To the best of our knowledge, there are only one case using the
      technique of arterial spin labeling (ASL) to detection and follow-up of perfusion
      changes in CJD. Herein, we described a 71-year-old woman presented with
      progressive cognitive decline, behavioral and psychological symptoms for two
      months. The patient died one month later after her admission. As far as we know,
      this is the first report using the combination of fluorodeoxyglucose positron
      emission tomography and ASL to explore the metabolism changes in sCJD. Our case
      exemplifies the difficulty clinicians may face in the diagnosis of sCJD.

PMID- 30223706
TI  - Neural activity reveals effects of aging on inhibitory processes during word
      retrieval.
AB  - Word retrieval difficulties are one of the most frustrating problems for older
      adults. Poorer access to phonological representation of the target word has been
      postulated as the underlying deficit, supported by findings of improved word
      retrieval after phonological priming. To better understand aging effects in the
      underlying neurophysiology associated with word retrieval, this study examined
      electrophysiological correlates of phonological priming and word retrieval in
      adults. Young, middle-aged, and older adults viewed pictures that were preceded
      by pseudo-word primes that either shared initial phonemes with or were unrelated
      to the picture's name. Participants made phonological judgments regarding the
      prime and picture prior to naming the picture. Behavioral and event-related
      potential correlates of phonological priming and word retrieval were recorded.
      All groups benefitted similarly from phonological priming, evidenced by faster
      phonological judgment response times and increased ease of word retrieval for
      primed pictures, indexed by the N400 priming effect. The peak latency of the N2,
      however, showed an incremental delay with age. High correlation between N2 peak
      latency and clinical measures of inhibition suggested an age-related delay in the
      inhibition of primed lexical competitors. Taken together, our results indicated
      intact activation of phonological representation of the picture's name but age
      related delays in inhibition of primed competitors. Interestingly, our findings
      revealed that delays in inhibiting lexical competitors may begin as early as
      middle age, highlighting the importance of including multiple age groups to
      better represent the aging trajectory.

PMID- 30223707
TI  - Intestinal macrophages in mucosal immunity and their role in systemic lupus
      erythematosus disease.
AB  - Monocytes play an important role in inducing host systemic immunity against
      invading pathogens and inflammatory responses. After activation, monocytes
      migrate to tissue sites, where they initiate both innate and adaptive immune
      responses, and become macrophages. Although mucosal macrophages produce
      inflammatory cytokines in response to pathogens, the perturbations in innate
      immune signaling pathway have been implicated in autoimmune diseases such as
      systemic lupus erythematosus (SLE). In this review, we focus on the role of human
      macrophages in intestinal innate immune responses, homeostasis, and SLE disease.
      We further discuss sex differences in the intestinal macrophages and their role
      in the physiology and pathogenesis of SLE.

PMID- 30223704
TI  - A simple in vitro assay for assessing the efficacy, mechanisms and kinetics of
      anti-prion fibril compounds.
AB  - Prion diseases are caused by the conversion of normal cellular prion proteins
      (PrP) into lethal prion aggregates. These prion aggregates are composed of
      proteinase K (PK) resistant fibrils and comparatively PK-sensitive oligomers.
      Currently there are no anti-prion pharmaceuticals available to treat or prevent
      prion disease. Methods of discovering anti-prion molecules rely primarily on
      relatively complex cell-based, tissue slice or animal-model assays that measure
      the effects of small molecules on the formation of PK-resistant prion fibrils.
      These assays are difficult to perform and do not detect the compounds that
      directly inhibit oligomer formation or alter prion conversion kinetics. We have
      developed a simple cell-free method to characterize the impact of anti-prion
      fibril compounds on both the oligomer and fibril formation. In particular, this
      assay uses shaking-induced conversion (ShIC) of recombinant PrP in a 96-well
      format and resolution enhanced native acidic gel electrophoresis (RENAGE) to
      generate, assess and detect PrP fibrils in a high throughput fashion. The end
      point PrP fibrils from this assay can be further characterized by PK analysis and
      negative stain transmission electron microscopy (TEM). This cell-free, gel-based
      assay generates metrics to assess anti-prion fibril efficacy and kinetics. To
      demonstrate its utility, we characterized the action of seven well-known anti
      prion molecules: Congo red, curcumin, GN8, quinacrine, chloropromazine,
      tetracycline, and TUDCA (taurourspdeoxycholic acid), as well as four suspected
      anti-prion compounds: trans-resveratrol, rosmarinic acid, myricetin and ferulic
      acid. These findings suggest that this in vitro assay could be useful in
      identifying and comprehensively assessing novel anti-prion fibril compounds.
      Abbreviations: PrP, prion protein; PK, proteinase K; ShIC, shaking-induced
      conversion; RENAGE, resolution enhanced native acidic gel electrophoresis; TEM,
      transmission electron microscopy; TUDCA, taurourspdeoxycholic acid; BSE, bovine
      spongiform encephalopathy; CWD, chronic wasting disease; CJD, Creutzfeldt Jakob
      disease; GSS, Gerstmann-Straussler-Scheinker syndrome; FFI, fatal familial
      insomnia; PrPc, cellular prion protein; recPrPC, recombinant monomeric prion
      protein; PrPSc, infectious particle of misfolded prion protein; RT-QuIC, real
      time quaking-induced conversion; PMCA, Protein Misfolding Cyclic Amplification;
      LPS, lipopolysaccharide; EGCG, epigallocatechin gallate; GN8, 2-pyrrolidin-1-yl-N
      [4-[4-(2-pyrrolidin-1-yl-acetylamino)-benzyl]-phenyl]-acetamide; DMSO, dimethyl
      sulfoxide; ScN2A, scrapie infected neuroblastoma cells; IC50, inhibitory
      concentration for 50% reduction; recMoPrP 23-231, recombinant full-length mouse
      prion protein residues 23-231; EDTA; PICUP, photo-induced cross-linking of
      unmodified protein; BSA, bovine serum albumin;; PMSF, phenylmethanesulfonyl
      fluoride.

PMID- 30223708
TI  - Working memory predicts subsequent episodic memory decline during healthy
      cognitive aging: evidence from a cross-lagged panel design.
AB  - Aging adults experience declines in working memory and episodic memory, however,
      it is unclear how these declines operate over time. Decreased working memory may
      be associated with early changes in episodic memory, by reducing older adults'
      ability to meaningfully integrate new information into pre-existing schemas and
      recall information without the assistance of cues. Given the increased prevalence
      of Alzheimer's disease, and concerns based on subjective memory changes, it is
      important to understand how these processes interact over time. To assess the
      relationship between working memory and episodic memory during healthy cognitive
      aging, we performed neuropsychological assessments at multiple time points in a
      sample of 310 community-dwelling older adults. Using a cross-lagged panel design,
      we demonstrated that the lagged associations between working memory and later
      episodic free recall were 50% larger than the lagged associations between
      episodic recall and later working memory, suggesting working memory may be a
      useful metric of future episodic memory decline.

PMID- 30223709
TI  - Freezing of Gait Boot Camp: feasibility, safety and preliminary efficacy of a
      community-based group intervention.
AB  - AIM: In this pilot study, we evaluated the feasibility, safety and preliminary
      efficacy of a 6-week, community-based group intervention designed to reduce
      freezing of gait (FOG) for people with Parkinson's disease (PD). METHODS: Seven
      people with PD completed 'FOG Boot Camp' provided by the St. Louis Chapter of the
      American Parkinson Disease Association. We recorded attendance, participant's
      acceptance of the intervention and adverse events during classes. Pre and post
      tests included measures of freezing, balance, motor severity, quality-of-life and
      gait speed. RESULTS: No falls or injuries occurred and attendance was high.
      Participants had favorable feedback and showed reduced freezing and improvements
      in balance and gait. CONCLUSION: Preliminary data suggest the FOG boot camp was
      feasible, safe and effective.

PMID- 30223710
TI  - Mini-Mental State Examination: diagnostic test accuracy study in primary care
      referrals.
AB  - AIM: To undertake a diagnostic test accuracy study of the Mini-Mental State
      Examination (MMSE) administered in primary care to patients who were subsequently
      referred to a cognitive disorders clinic in secondary care (n = 72). METHODS:
      MMSE scores from primary care were cross-classified with reference standard
      diagnoses made in secondary care, blind to MMSE score, in order to calculate
      standard measures of discrimination (including sensitivity and specificity,
      positive and negative predictive values). RESULTS: MMSE showed poor sensitivity
      (0.64) but better specificity (0.80) for diagnosis of any cognitive impairment at
      the index paper specified cut-off, with little additional benefit using a more
      stringent cut-off. CONCLUSION: These data suggest MMSE is not suitable for
      screening for cognitive impairment in the low prevalence setting of primary care.

PMID- 30223711
TI  - Speech disorders in Parkinson's disease: pathophysiology, medical management and
      surgical approaches.
AB  - The prevalence of speech disorders among individuals with Parkinson's disease
      (PD) has been reported to be as high as 89%. Speech impairment in PD results from
      a combination of motor and nonmotor deficits. The production of speech depends
      upon the coordination of various motor activities: respiration, phonation,
      articulation, resonance and prosody. A speech disorder is defined as impairment
      in any of its inter-related components. Despite the high prevalence of speech
      disorders in PD, only 3-4% receive speech treatment. Treatment modalities include
      pharmacological intervention, speech therapy, surgery, deep brain stimulation and
      vocal fold augmentation. Although management of Parkinsonian dysarthria is
      clinically challenging, speech treatment in PD should be part of a
      multidisciplinary approach to patient care in this disease.

PMID- 30223712
TI  - Exploring fair decision-making rules in nursing: A qualitative study.
AB  - BACKGROUND: The decision-making process should be done according to a set of
      rules and principles so as to be fairly understood. OBJECTIVES: The aim of this
      study was to identify the basic principles and rules used by nurses to understand
      justice in nurse managers' decision-making processes based on a procedural
      justice model. Research design and participants: This research was a qualitative
      study based on directed content analysis, which was performed on a group of 15
      nurses working in different hospitals in Tehran, Iran. An in-depth semi
      structured interview was used as the method of data collection for this study.
      Ethical consideration: This research has been approved by the Ethics Committee of
      the University of Social Welfare and Rehabilitation Sciences. The respondents
      were informed about the aim of the study, about voluntary participation,
      anonymity and confidentiality. FINDINGS: The results of this study showed that in
      order to understand procedural justice, nurses use several rules, including:
      duties organization, managerial support, consistency, bias-suppression, accuracy,
      correctability, representativeness, and ethicality. CONCLUSION: Nursing leaders
      must consider the importance of justice rules as one of many strategies to ensure
      the nurses' perception of fairness in decision-making processes.

PMID- 30223714
TI  - Assessing the benefit of treatment in chronic inflammatory demyelinating
      polyneuropathy: the challenges of clinical practice.

PMID- 30223715
TI  - Technique modifications for a suction suspension version of the Northwestern
      University Flexible Sub-Ischial Vacuum socket: The Northwestern University
      Flexible Sub-Ischial Suction socket.
AB  - BACKGROUND AND AIM: Development of a passive suction version of the Northwestern
      University Flexible Sub-Ischial Vacuum socket would expand application of sub
      ischial sockets to a larger proportion of persons with transfemoral amputation.
      While active vacuum suspension provides more positive coupling of the residual
      limb to the prosthetic socket, there are circumstances when use of active vacuum
      is not appropriate or feasible. Therefore, this technical note describes the
      technique modifications required to cast, fabricate, and fit a passive suction
      version of the Northwestern University Flexible Sub-Ischial Vacuum socket (i.e.
      the Northwestern University Flexible Sub-Ischial Suction socket). TECHNIQUE: Most
      technique modifications stem from the use of an internal seal with the
      Northwestern University Flexible Sub-Ischial Suction socket and the need to
      account for the greater relative motion occurring between the residual limb and
      socket with passive suction compared to active vacuum suspension. DISCUSSION:
      Between January 2015 and March 2018, 266 Northwestern University Flexible Sub
      Ischial Suction sockets were fit successfully using the described technique
      modifications. Clinical relevance A passive suction version of the Northwestern
      University Flexible Sub-Ischial Vacuum socket-the Northwestern University
      Flexible Sub-Ischial Suction socket-broadens the application of sub-ischial
      sockets to a larger proportion of the population with transfemoral amputation.

PMID- 30223713
TI  - Evaluation of methodologies for microRNA biomarker detection by next generation
      sequencing.
AB  - In recent years, microRNAs (miRNAs) in tissues and biofluids have emerged as a
      new class of promising biomarkers for numerous diseases. Blood-based biomarkers
      are particularly desirable since serum or plasma is easily accessible and can be
      sampled repeatedly. To comprehensively explore the biomarker potential of miRNAs,
      sensitive, accurate and cost-efficient miRNA profiling techniques are required.
      Next generation sequencing (NGS) is emerging as the preferred method for miRNA
      profiling; offering high sensitivity, single-nucleotide resolution and the
      possibility to profile a considerable number of samples in parallel. Despite the
      excitement about miRNA biomarkers, challenges associated with insufficient
      characterization of the sequencing library preparation efficacy, precision and
      method-related quantification bias have not been addressed in detail and are
      generally underappreciated in the wider research community. Here, we have tested
      in parallel four commercially available small RNA sequencing kits against a
      cohort of samples comprised of human plasma, human serum, murine brain tissue and
      a reference library containing ~ 950 synthetic miRNAs. We discuss the advantages
      and limits of these methodologies for massive parallel microRNAs profiling. This
      work can serve as guideline for choosing an adequate library preparation method,
      based on sensitivity, specificity and accuracy of miRNA quantification, workflow
      convenience and potential for automation.

PMID- 30223716
TI  - Immigrants' Use of eHealth Services in the United States, National Health
      Interview Survey, 2011-2015.
AB  - OBJECTIVES:: Little is known about the use of electronic health (eHealth)
      services supported by information technology in the United States among
      immigrants, a group that faces barriers in accessing care and, consequently,
      disparities in health outcomes. We examined differences in the use of eHealth
      services in the United States by immigration status in a nationally
      representative sample. METHODS:: We used data from the 2011-2015 National Health
      Interview Survey to assess use of eHealth services among US natives, naturalized
      citizens, and noncitizens. Our outcome variable of interest was respondent
      reported use of eHealth services, defined as making medical appointments online,
      refilling prescriptions online, or communicating with health care professionals
      through email, during the past 12 months. We analyzed use of eHealth services,
      demographic characteristics, socioeconomic status, and health status among all 3
      groups. We used multivariate logistic regression models to examine the
      association between immigration status and the likelihood of using eHealth
      services, adjusting for individual demographic, socioeconomic, and health
      characteristics. RESULTS:: Among 126 893 US natives, 18 763 (16.1%) reported
      using any eHealth services in the past 12 months, compared with 1738 of 15 102
      (13.0%) naturalized citizens and 1020 of 14 340 (7.8%) noncitizens. Adjusting for
      socioeconomic factors reduced initial gaps: naturalized citizens (adjusted odds
      ratio [aOR] = 0.81; 95% confidence interval [CI], 0.75-0.87) and noncitizens (aOR
      = 0.81; 95% CI, 0.72-0.90) had approximately 20% lower odds of using eHealth
      services than did US natives. However, the differences varied by type of eHealth
      service. Immigrants with higher English-language proficiency were more likely to
      use eHealth services than were immigrants with lower English-language
      proficiency. CONCLUSIONS:: Targeted interventions that reduce socioeconomic
      barriers in accessing technology and promote multilingual electronic portals
      could help mitigate disparities in use of eHealth services.

PMID- 30223717
TI  - Development of the Youth Emotion Picture Set.
AB  - Several facial expression image sets have been developed. Nevertheless, there is
      a lack of facial expression sets comprising adolescents' images depicting all
      basic emotions. This study aimed to fill this gap through the development of an
      image database of youth facial expressions, containing pictures of six basic
      emotions plus neutral. Posed and spontaneous expressions were collected from 31
      youths, 12 to 20 years old; 2,279 frames were obtained, and an initial screening
      was conducted through the exclusion of similar frames, low intensity images, and
      ambiguous or blended expressions; 256 frames met criteria and were rechecked by
      two expert judges. Images were retained if they depicted all the prototypical
      features of the designated expression. A final selection was conducted to assure
      an image set that covered all age ranges, both sexes and an even number of images
      by expression, resulting in 42 frames (21 male, six of each emotion). Expert
      judges, independent adults, independent teenagers, and a software validation were
      used to assure database validity. Agreement across raters was high, and no
      differences were observed for posed and spontaneous images. The data set
      developed in this study can be a valid tool in studies of facial expressions, in
      particular, with adolescents' samples.

PMID- 30223718
TI  - Prediction of in vivo lower cervical spinal loading using musculoskeletal multi
      body dynamics model during the head flexion/extension, lateral bending and axial
      rotation.
AB  - Cervical spine diseases lead to a heavy economic burden to the individuals and
      societies. Moreover, frequent post-operative complications mean a higher risk of
      neck pain and revision. At present, controversy still exists for the etiology of
      spinal diseases and their associated complications. Knowledge of in vivo cervical
      spinal loading pattern is proposed to be the key to answer these questions.
      However, direct acquisition of in vivo cervical spinal loading remains
      challenging. In this study, a previously developed cervical spine musculoskeletal
      multi-body dynamics model was utilized for spinal loading prediction. The in vivo
      dynamic segmental contributions to head motion and the out-of-plane coupled
      motion were both taken into account. First, model validation and sensitivity
      analysis of different segmental contributions to head motion were performed. For
      model validation, the predicted intervertebral disk compressive forces were
      converted into the intradiskal pressures and compared with the published
      experimental measurements. Significant correlations were found between the
      predicted values and the experimental results. Thus, the reliability and
      capability of the cervical spine model was ensured. Meanwhile, the sensitivity
      analysis indicated that cervical spinal loading is sensitive to different
      segmental contributions to head motion. Second, the compressive, shear and facet
      joint forces at C3-C6 disk levels were predicted, during the head
      flexion/extension, lateral bending and axial rotation. Under the head
      flexion/extension movement, asymmetric loading patterns of the intervertebral
      disk were obtained. In comparison, symmetrical typed loading patterns were found
      for the head lateral bending and axial rotation movements. However, the shear
      forces were dramatically increased during the head excessive extension and
      lateral bending. Besides, a nonlinear correlation was seen between the facet
      joint force and the angular displacement. In conclusion, dynamic cervical spinal
      loading was both intervertebral disk angle-dependent and level-dependent.
      Cervical spine musculoskeletal multi-body dynamics model provides an attempt to
      comprehend the in vivo biomechanical surrounding of the human head-neck system.

PMID- 30223719
TI  - Public Health, Racism, and the Lasting Impact of Hospital Segregation.

PMID- 30223720
TI  - The Pathological Features of Colorectal Cancer Determine the Detection
      Performance on Blood ctDNA.
AB  - BACKGROUND AND AIM: Methylated SEPT9 is a novel circulating tumor DNA marker for
      colorectal cancer, while the effects of various colorectal cancer
      clinicopathological factors on its detection performance have not been fully
      evaluated. This study aims to investigate the significance of the
      clinicopathological factors on methylated SEPT9 performance in a symptomatic
      endoscopy cohort, with a specific focus on colorectal cancer. METHODS: A total of
      1160 participants were recruited in this study, including 300 patients with
      colorectal cancer, 122 patients with adenoma, 103 patients with hyperplastic
      polyps, 568 normal participants (no evidence of disease), and 67 patients with
      other gastrointestinal diseases. Peripheral blood samples of these participants
      were collected from 3 Chinese hospitals, and the methylated SEPT9 level was
      measured using the Epi proColon 2.0 assay. RESULTS: Cancer stage, size, and
      invasion depth were positively correlated with the detection sensitivity, while
      no difference in sensitivity was identified among cancers at various locations.
      Infiltrative colorectal cancer exhibited higher sensitivity than ulcerative and
      protrude colorectal cancer, while no difference in sensitivity was observed among
      assessed histological types. The colorectal cancer differentiation showed a clear
      correlation with the cancer stage, and moderate and poorly differentiated
      colorectal cancer exhibited higher sensitivity than well-differentiated
      colorectal cancer. Furthermore, colorectal cancer with distal metastasis (M1)
      showed higher sensitivity than those without any metastasis, while colorectal
      cancer with lymph node metastasis (N1 and N2) did not show statistical
      significance compared to those without it. Finally, local vessel or nerve
      invasion did not affect the sensitivity. CONCLUSION: Factors that reflect the
      colorectal cancer intrinsic properties, including cancer stage, size, invasion
      depth, classification, differentiation, and metastasis, exhibited significant
      effect on the mSEPT9 detection performance.

PMID- 30223721
TI  - Hypoglossal Nerve Stimulation and Heart Rate Variability: Analysis of STAR Trial
      Responders.
AB  - Objective Hypoglossal nerve stimulation represents a novel therapy for the
      treatment of moderate-severe obstructive sleep apnea; nonetheless, its
      cardiovascular effects are not known. We examine the effects of hypoglossal nerve
      stimulation on heart rate variability, a measure of autonomic function. Study
      Design Substudy of the STAR trial (Stimulation Therapy for Apnea Reduction): a
      multicenter prospective single-group cohort. Setting Academic and private
      practice centers in the United States and Europe. Subjects and Methods A subset
      of responder participants (n = 46) from the STAR trial was randomized to therapy
      withdrawal or therapy maintenance 12 months after surgery. Heart rate variability
      analysis included standard deviation of the R-R interval (SDNN), low-frequency
      power of the R-R interval, and high-frequency power of the R-R interval. Analysis
      was performed by sleep with 5-minute sliding window epochs during baseline, 12
      months, and the maintenance/withdrawal period. Results A significant improvement
      from baseline to 12 months in heart rate variability was seen for SDNN and low
      frequency across all sleep stages. SDNN analysis demonstrated no change in the
      wake period (mean +/- SD: 0.042 +/- 0.01 vs 0.077 +/- 0.07, P = .19). Reduction
      in SDNN was correlated to improvement in apnea-hypopnea index ( r = 0.39, P =
      .03). In the therapy withdrawal group, no significant changes in SDNN were seen
      for N1/N2, N3, or rapid eye movement sleep. Conclusion Hypoglossal nerve
      stimulation therapy appears to reduce heart rate variability during sleep. This
      reduction was not affected by a 1-week withdrawal period. Larger prospective
      studies are required to better understand the effect of hypoglossal nerve
      stimulation on autonomic dysfunction in obstructive sleep apnea.

PMID- 30223722
TI  - Using Back-Table Angioscopy to Evaluate Renal Allograft Arterial Injury.

PMID- 30223723
TI  - Acute Hypoxia and Chronic Ischemia Induce Differential Total Changes in Placental
      Epigenetic Modifications.
AB  - Preeclampsia is a common obstetrical complication, hallmarked by new-onset
      hypertension. Believed to result from placental insufficiency and chronic
      placental ischemia, the symptoms of preeclampsia are caused by release of
      pathogenic factors from the placenta itself, although the mechanisms of their
      regulation are in many cases unknown. One potential mechanism is through changes
      in placental epigenetic chromatin modifications, particularly histone acetylation
      and DNA methylation. Here, we determined the effects of chronic ischemia on
      global epigenetic modifications in the rodent placenta in vivo and acute hypoxia
      in BeWo placental trophoblast cells in vitro. Placental insufficiency via uterine
      artery restriction increased maternal blood pressure and fetal demise while
      decreasing placental and fetal mass. Global placental histone H3 acetylation
      levels were significantly decreased at H3 K9, K14, K18, K27, and K56.
      Interestingly, when BeWo-immortalized placental trophoblast cells were cultured
      in oxygen concentrations mimicking healthy and ischemic placentas, there was a
      significant increase in acetylated at K9, K18, K27, and K56. This was associated
      with a small but significant decrease in placental acetyl-CoA, suggesting
      depletion in the source of acetyl group donors. Finally, while global methylation
      of cytosine from placental DNA was low in both groups of animals (<1%), there was
      ~50% increase in 5-mC in response to chronic ischemia. This suggests acute
      hypoxia and chronic ischemia induce differential global changes in histone
      acetylation in the placenta and that chronically altered metabolic profiles could
      affect histone acetylation in the placenta, thereby regulating production of
      pathogenic factors from the placenta during preeclampsia.

PMID- 30223725
TI  - Spontaneous Accessory Renal Artery Aneurysm Rupture in a Patient With
      Neurofibromatosis Type 1: A Case Report.
AB  - True renal artery aneurysms are rare. Ruptured aneurysms are even rarer but can
      have devastating consequences. Renal artery aneurysms most commonly occur in
      patients with hypertension, atherosclerosis, or fibromuscular dysplasia.
      Treatment options can range from embolization to nephrectomy. We describe an
      interesting case of spontaneous accessory renal artery aneurysm rupture in a 44
      year-old female with neurofibromatosis type 1 (NF1) who otherwise had no medical
      problems. She was successfully treated with selective coil embolization,
      recovered without complications, and maintained preoperative renal function.

PMID- 30223724
TI  - Absenteeism and Delay to Work Due to Sleep Disorders in the Turkish Adult
      Population: A Questionnaire-Based National Survey.
AB  - Sleep problems may have negative effects on work-life balance, overall health,
      and safety. We aimed to investigate the association between sleep disorders and
      absenteeism and delay to work (being late or tardy) among the working adult
      population. The study was conducted by using data from a large survey of working
      adults who participated in the Turkish Adult Population Epidemiology of Sleep
      Study (TAPES) managed by Turkish Sleep Medicine Society (TSMS). Secondary
      analyses was employed to examine absenteeism and delay to work and their
      associations with sleep problems, including sleepiness by Epworth Sleepiness
      Scale (ESS), parasomnias, sleep apnea (by Berlin Questionnaire), sleep quality
      (by Pittsburgh Sleep Quality Index), and restless leg. History of any absenteeism
      and delay to work was observed in 276 (18%) and 443 (29%) out of 1,533 working
      adults, respectively. In the multivariate analyses, absenteeism was associated
      with younger age, female gender and poor sleep quality, while delay to work was
      associated with younger age, poor sleep quality, parasomnia, and sleepiness. In
      the presence of absenteeism and delay to work, sleep disorders including
      sleepiness, poor sleep quality, and parasomnia should be considered. Such
      evaluation may improve worker well-being and provide some additional benefits in
      terms of increasing productivity and lowering work-related costs.

PMID- 30223726
TI  - Self-Reported Skin Disorders Among Health Care Workers.
AB  - This study aimed to estimate the point prevalence and 1-year period prevalence of
      skin disorder symptoms (SDS) among health care workers (HCWs) and to explore the
      possible risk factors. A random sample of 400 HCWs from 13 government health
      centers in Brunei Darussalam self-administered an adapted Nordic Occupational
      Skin Questionnaire (NOSQ-2002/SHORT). The point and 1-year prevalence of SDS were
      12% and 19%, respectively. Having a history of SDS before the current job,
      exposure to SDS-exacerbating materials at the workplace, and having clinical
      roles were correlated for both prevalence estimates. Frequent handwashing and
      moderate use of latex gloves were associated with higher risk of SDS at 1-year.
      Female HCWs were more likely to report SDS. In multivariate analyses, only
      contact with SDS-exacerbating materials at the workplace, prejob SDS, and
      moderate glove usage were significant predictors of SDS.

PMID- 30223727
TI  - Fetal Membrane Inflammation Induces Preterm Birth Via Toll-Like Receptor 2 in
      Mice With Chronic Gingivitis.
AB  - Inflammation is associated with preterm birth. We previously described a mouse
      model of chronic inflammation-induced preterm birth after dental Porphyromonas
      gingivalis infection. The aim of this study was to employ this model system to
      investigate the mechanisms through which enhanced uterine contractility induces
      preterm birth. Messenger RNA (mRNA) encoding contraction-associated proteins,
      such as oxytocin receptors, was measured at various gestational time points by
      real-time polymerase chain reaction (PCR). Spontaneous and oxytocin-induced
      uterine contractile activity at gestational day 18 was assessed using a tissue
      organ bath. The expression levels of Toll-like receptor 2 (TLR2), TLR4,
      cyclooxygenase (COX)-2, nuclear factor-kappa B (NF-kappaB) p65, and p38 mitogen
      activated protein kinase (MAPK) on gestational day 18 were also determined by
      real-time PCR or Western blotting. Messenger RNA encoding contraction-associated
      proteins was increased at gestational day 18, and the spontaneous contractile
      activity (1.6-fold greater area under the contraction curve) and sensitivity to
      oxytocin (EC50: 8.8 nM vs 2.2 nM) were enhanced in the P gingivalis group
      compared to those in the control group. In the P gingivalis group, COX-2 mRNA
      expression was not elevated in the placenta or myometrium but was upregulated 2.3
      fold in the fetal membrane. The TLR2 mRNA levels in the fetal membrane were 2.7
      fold higher in the P gingivalis group, whereas TLR4 levels were not elevated.
      Activation of the NF-kappaB p65 and p38 MAPK pathways was enhanced in the fetal
      membrane of the P gingivalis group. Thus, in mice with chronic dental P
      gingivalis infection, TLR2-induced inflammation in the fetal membrane leads to
      upregulation of uterine contractility, leading to preterm birth.

PMID- 30223728
TI  - Frequent, short bouts of light-intensity exercises while standing decreases
      systolic blood pressure: Breaking Up Sitting Time after Stroke (BUST-Stroke)
      trial.
AB  - BACKGROUND: Stroke survivors sit for long periods each day. Uninterrupted sitting
      is associated with increased risk of cardiovascular disease. Breaking up
      uninterrupted sitting with frequent, short bouts of light-intensity physical
      activity has an immediate positive effect on blood pressure and plasma clotting
      factors in healthy, overweight, and type 2 diabetic populations. AIM: We examined
      the effect of frequent, short bouts of light-intensity physical activity on blood
      pressure and plasma fibrinogen in stroke survivors. METHODS: Prespecified
      secondary analyses from a three-armed randomized, within-participant, crossover
      trial. Participants were 19 stroke survivors (nine female, aged 68 years old, 90%
      able to walk independently). The experimental conditions were sitting for 8 h
      uninterrupted, sitting with 3 min bouts of light-intensity exercise while
      standing every 30 min, or sitting with 3 min of walking every 30 min. Blood
      pressure was measured every 30 min over 8 h and plasma fibrinogen at the
      beginning, middle, and end of each day. Intention-to-treat analyses were
      performed using linear mixed models including fixed effects for condition,
      period, and order, and a random intercept for participant to account for repeated
      measures and missing data. RESULTS: Sitting with 3 min bouts of light-intensity
      exercise while standing every 30 min decreased systolic blood pressure by 3.5
      mmHg (95% CI 1.7-5.4) compared with sitting for 8 h uninterrupted. For
      participants not taking antihypertensive medications, sitting with 3 min of
      walking every 30 min decreased systolic blood pressure by 5.0 mmHg (95% CI -7.9
      to 2.0) and sitting with 3 min bouts light-intensity exercise while standing
      every 30 min decreased systolic blood pressure by 4.2 mmHg (95% CI -7.2 to -1.3)
      compared with sitting for 8 h uninterrupted. There was no effect of condition on
      diastolic blood pressure (p = 0.45) or plasma fibrinogen levels (p = 0.91).
      CONCLUSION: Frequent, short bouts of light-intensity physical activity decreases
      systolic blood pressure in stroke survivors. However, before translation into
      clinical practice, the optimal duration and timing of physical activity bouts
      needs to be determined. CLINICAL TRIAL REGISTRATION: Australian and New Zealand
      Clinical Trials Registry http://www.anzctr.org.au ANZTR12615001189516.

PMID- 30223730
TI  - In vivo tissue response and antibacterial efficacy of minocycline delivery system
      based on polymethylmethacrylate bone cement.
AB  - This study aims the in vivo biological characterization of an innovative
      minocycline delivery system, based on polymethylmethacrylate bone cement. Bone
      cements containing 1% or 2.5% (w/w) minocycline were formulated and evaluated
      through solid-state characterization. Biological evaluation was conducted in
      vivo, within a rat model, following the subcutaneous and bone tissue
      implantation, and tissue implantation associated with Staphylococcus aureus is
      challenging. The assessment of the tissue/biomaterial interaction was conducted
      by histologic, histomorphometric and microtomographic techniques. Minocycline
      addition to the composition of the polymethylmethacrylate bone cement did not
      modify significantly the cement properties. Drug release profile was marked by an
      initial burst release followed by a low-dosage sustained release. Following the
      subcutaneous tissue implantation, a reduced immune-inflammatory reaction was
      verified, with diminished cell recruitment and a thinner fibro-connective capsule
      formation. Minocycline-releasing cements were found to enhance the bone-to
      implant contact and bone tissue formation, following the tibial implantation.
      Lastly, an effective antibacterial activity was mediated by the implanted cement
      following the tissue challenging with S. aureus. Kinetic minocycline release
      profile, attained with the developed polymethylmethacrylate system, modulated
      adequately the in vivo biological response, lessening the immune-inflammatory
      activation and enhancing bone tissue formation. Also, an effective in vivo
      antibacterial activity was established. These findings highlight the adequacy and
      putative application of the developed system for orthopedic applications.

PMID- 30223731
TI  - Carrageenan hydrogel as a scaffold for skin-derived multipotent stromal cells
      delivery.
AB  - Carrageenan is a thermoreversible polymer of natural origin widely used in food
      and pharmaceutical industry that presents a glycosaminoglycan-like structure.
      Herein, we show that kappa-type carrageenan extracted by a semi-refined process
      from the red seaweed Kappaphycus alvarezii displayed both chemical and structural
      properties similar to a commercial carrageenan. Moreover, both extracted
      carrageenan hydrogel and commercial carrageenan hydrogel can serve as a scaffold
      for in vitro culture of human skin-derived multipotent stromal cells,
      demonstrating considerable potential as cell-carrier materials for cell delivery
      in tissue engineering. Skin-derived multipotent stromal cells cultured inside the
      carrageenan hydrogels showed a round shape morphology and maintained their growth
      and viability for at least one week in culture. Next, the effect of the extracted
      carrageenan hydrogel loaded with human skin-derived multipotent stromal cells was
      evaluated in a mouse model of full-thickness skin wound. Macroscopic and
      histological analyses revealed some pointed ameliorated features, such as reduced
      inflammatory process, faster initial recovery of wounded area, and improved
      extracellular matrix deposition. These results indicate that extracted
      carrageenan hydrogel can serve as a scaffold for in vitro growth and maintenance
      of human SD-MSCs, being also able to act as a delivery system of cells to wounded
      skin. Thus, evaluation of the properties discussed in this study contribute to a
      further understanding and specificities of the potential use of carrageenan
      hydrogel as a delivery system for several applications, further to skin wound
      healing.

PMID- 30223732
TI  - Tailored antimicrobial activity and long-term cytocompatibility of plasma polymer
      silver nanocomposites.
AB  - The deposition of coatings enabling antibacterial properties in combination with
      cytocompatibility remains a challenge for biomaterial applications, such as in
      medical devices. Silver is one of the most utilized antibacterial surface
      components, due to its efficacy and extensive applicability. In this work, silver
      containing plasma polymer nanocomposites (single layer and multilayers) were
      developed and tested, with a focus on cytotoxicity and bactericidal function, on
      the NIH3T3 mammalian cell line as well as Gram-negative ( Pseudomonas aeruginosa)
      and Gram-positive ( Staphylococcus aureus) bacterial strains. The data
      demonstrate that a tuneable Ag+ release is required, allowing sufficient
      antimicrobial activity while retaining appropriate cytocompatibility over the
      entire testing period of up to eight days.

PMID- 30223733
TI  - Chitosan enhances gene delivery of oligonucleotide complexes with magnetic
      nanoparticles-cell-penetrating peptide.
AB  - Gene-based therapies, including the delivery of oligonucleotides, offer promising
      methods for the treatment of cancer cells. However, they have various limitations
      including low efficiency. Herein, cell-penetrating peptides (CPPs)-conjugated
      chitosan-modified iron oxide magnetic nanoparticles (CPPs-CTS@MNPs) with high
      biocompatibility as well as high efficiency were tested for the delivery of
      oligonucleotides such as plasmid pGL3, splice correction oligonucleotides, and
      small-interfering RNA. A biocompatible nanocomposite, in which CTS@MNPs was
      incorporated in non-covalent complex with CPPs-oligonucleotide, is developed.
      Modifying the surface of magnetic nanoparticles with cationic chitosan-modified
      iron oxide improved the performance of magnetic nanoparticles-CPPs for
      oligonucleotide delivery. CPPs-CTS@MNPs complexes enhance oligonucleotide
      transfection compared to CPPs@MNPs or CPPs. The hydrophilic character of CTS@MNPs
      improves complexation with plasmid pGL3, splice correction oligonucleotides, and
      small-interfering RNA payload, which consequently resulted in not only
      strengthening the colloidal stability of the constructed complex but also
      improving their biocompatibility. Transfection using PF14-splice correction
      oligonucleotides-CTS@MNPs showed sixfold increase of the transfection compared to
      splice correction oligonucleotides-PF14 that showed higher transfection than the
      commercially available lipid-based vector LipofectamineTM 2000. Nanoscaled CPPs
      CTS@MNPs comprise a new family of biomaterials that can circumvent some of the
      limitations of CPPs or magnetic nanoparticles.

PMID- 30223734
TI  - Effects of calcium and phosphorus incorporation on the properties and bioactivity
      of TiO2 nanotubes.
AB  - In this study, we investigate the formation of calcium and phosphorus-doped TiO2
      nanotubes, produced by potentiostatic anodization of Ti in viscous electrolyte
      containing HF and Ca/P ions. Characterization of the produced oxide layer was
      conducted using scanning electron microscopy, glancing-angle X-ray diffraction, X
      ray photoelectron spectroscopy, contact angle, and protein adsorption
      measurements. Adipose-derived stem cells were used to study material
      cytotoxicity, cell viability and proliferation, and cell morphology and growth.
      To evaluate the adipose-derived stem-cell differentiation, we investigated the
      expression of osteocalcin and osteopontin by cells as well as calcium
      mineralization. Results show that it was possible to produce a superhydrophilic
      titanium oxide nanotube layer with incorporation of Ca and P ions. The presence
      of Ca and P in the oxide layer not only improved the cell adhesion and
      proliferation but also stimulated the production of key marker proteins
      indicating differentiation of cells.

PMID- 30223735
TI  - Sustained drug release using cobalt oxide nanowires for the preparation of
      polymer-free drug-eluting stents.
AB  - Polymer-based drug-eluting stents (DESs) represented attractive application for
      the treatment of cardiovascular diseases; however, polymer coating has caused
      serious adverse responses to tissues such as chronic inflammation due to acidic
      by-products. Therefore, polymer-free DESs have recently emerged as promising
      candidates for the treatment; however, burst release of drug(s) from the surface
      limited its applications. In this study, we focused on delivery of therapeutic
      drug from polymer-free (or -less) DESs through surface modification using cobalt
      oxide nanowires (Co3O4 NWs) to improve and control the drug release. The results
      demonstrated that Co3O4 NWs could be simply fabricated on cobalt-chromium
      substrate by ammonia-evaporation-induced method. The Co3O4 NWs were uniformly
      arrayed with diameters of 50-100 nm and lengths of 10 um. It was found that Co3O4
      NWs were comparatively stable without any delamination or change of the
      morphology under in vitro long-term stability using circulating system. Sirolimus
      was used as a model drug for studying in vitro release behavior under
      physiological conditions. The sirolimus release behavior from flat cobalt
      chromium showed an initial burst (over 90%) after one day. On the other hand,
      Co3O4 NWs presented a sustained sirolimus release rate for up to seven days.
      Similarly, the polymer-less specimens on Co3O4 NWs substrates sustained sirolimus
      release for a longer-period of time when compared to flat Co-Cr substrates. In
      summary, the current approach of using Co3O4 NWs-based substrates might have a
      great potential to sustain drug release for drug-eluting implants and medical
      devices including stents.

PMID- 30223736
TI  - Development of a novel hybrid bioactive hydrogel for future clinical
      applications.
AB  - Three-dimensional hydrogels are ideal for tissue engineering applications due to
      their structural integrity and similarity to native soft tissues; however, they
      can lack mechanical stability. Our objective was to develop a bioactive and
      mechanically stable hydrogel for clinical application. Auricular cartilage was
      decellularised using a combination of hypertonic and hypotonic solutions with and
      without enzymes to produce acellular tissue. Methacryloyl groups were crosslinked
      with alginate and PVA main chains via 2-aminoethylmathacrylate and the entire
      macromonomer further crosslinked with the acellular tissue. The resultant
      hydrogels were characterised for its physicochemical properties (using NMR), in
      vitro degradation (via GPC analysis), mechanical stability (compression tests)
      and in vitro biocompatibility (co-culture with bone marrow-derived mesenchymal
      stem cells). Following decellularisation, the cartilage tissue showed to be
      acellular at a significant level (DNA content 25.33 ng/mg vs. 351.46 ng/mg
      control tissue), with good structural and molecular integrity of the retained
      extra cellular matrix (s-GAG= 0.19 MUg/mg vs. 0.65 MUg/mg +/-0.001 control
      tissue). Proteomic analysis showed that collagen subtypes and proteoglycans were
      retained, and SEM and TEM showed preserved matrix ultra-structure. The hybrid
      hydrogel was successfully cross-linked with biological and polymer components,
      and it was stable for 30 days in simulated body fluid (poly dispersal index for
      alginate with tissue was stable at 1.08 and for PVA with tissue was stable at
      1.16). It was also mechanically stable (Young's modulus of 0.46 +/- 0.31 KPa) and
      biocompatible, as it was able to support the development of a multi-cellular
      feature with active cellular proliferation in vitro. We have shown that it is
      possible to successfully combine biological tissue with both a synthetic and
      natural polymer and create a hybrid bioactive hydrogel for clinical application.

PMID- 30223737
TI  - Preparation and characterization of porous hydroxyapatite/beta-cyclodextrin-based
      polyurethane composite scaffolds for bone tissue engineering.
AB  - In this study, novel porous scaffolds containing hydroxyapatite and beta
      cyclodextrin-based polyurethane were first successfully fabricated by
      polymerizing beta-cyclodextrin with hexamethylene diisocyanate and hydroxyapatite
      in situ for bone tissue engineering. The physicochemical and mechanical
      properties as well as cytocompatibility of porous scaffolds were investigated.
      The results showed that polyurethane reinforced with hydroxyapatite composites
      had cancellous bone-like porous structure. The mechanical strength of the
      scaffolds increased with increasing the hydroxyapatite content in scaffolds.
      Synthesized scaffolds (PU1, PUHA1, PU2, and PUHA2) presented compressive strength
      values of 0.87 +/- 0.24 MPa, 1.81 +/- 0.10 MPa, 6.16 +/- 0.89 MPa, and 12.95 +/-
      2.05 MPa, respectively. The pore size and porosity of these scaffolds were
      suitable for bone regeneration. Cytocompatibility of composite scaffolds was
      proven via favorable interactions with MC3T3-E1 cells. The addition of
      hydroxyapatite into CD-based polyurethane scaffolds improved cell attachment,
      well-spread morphology, and higher proliferation. The hydroxyapatite-polyurethane
      scaffolds have the potential to be applied in bone repair and regeneration.

PMID- 30223739
TI  - Children With Cerebral Palsy Have Greater Stride-to-Stride Variability of Muscle
      Synergies During Gait Than Typically Developing Children: Implications for Motor
      Control Complexity.
AB  - BACKGROUND: There is mounting evidence that the central nervous system utilizes a
      modular approach for neuromuscular control of walking by activating groups of
      muscles in units termed muscle synergies. Examination of muscle synergies in
      clinical populations may provide insights into alteration of neuromuscular
      control underlying pathological gait patterns. Previous studies utilizing synergy
      analysis have reported reduced motor control complexity during walking in those
      with neurological deficits, revealing the potential clinical utility of this
      approach. METHODS: We extracted muscle synergies on a stride-to-stride basis from
      20 children with cerebral palsy (CP; Gross Motor Function Classification System
      levels I-II) and 8 children without CP, allowing the number of synergies to vary
      for each stride. Similar muscle synergies across all participants and strides
      were grouped using a k-means clustering and discriminant analysis. RESULTS: In
      total, 10 clusters representing 10 distinct synergies were found across the 28
      individuals. Relative to their total number of synergies deployed during walking,
      synergies from children with CP were present in a higher number of clusters than
      in children with typical development (TD), indicating significantly greater
      stride-to-stride variability. This increased variability was present despite
      reduced complexity, as measured by the mean number of synergies in each stride.
      Whereas children with CP demonstrate some novel synergies, they also deploy some
      of the same muscle synergies as those with TD, although less frequently and with
      more variability. CONCLUSION: A stride-by-stride approach to muscle synergy
      analysis expands its clinical utility and may provide a method to tailor
      rehabilitation strategies by revealing inconsistent but functional synergies in
      each child with CP.

PMID- 30223740
TI  - Growth in Focused Topics: Children and Youth.

PMID- 30223741
TI  - Factors That Influence Parental Uncertainty and Health-Related Quality of Life in
      Children With Cancer: A Framework.
AB  - The purpose of this paper is to present a conceptual-theoretical-empirical model
      addressing factors that influence the relation between parental uncertainty and
      health-related quality of life in children with cancer. The basic concepts
      identified and defined in the model include parental uncertainty, health-related
      quality of life, parental trait anxiety, parental depression, and perceived
      parental social support. The proposed relationships between the concepts are
      explained with explicit linkages to their empirical indicators. There is limited
      research in childhood cancer regarding the relation between parental uncertainty
      and health-related quality of life; therefore, the proposed model will help to
      better understand this relationship.

PMID- 30223738
TI  - Exosomes and Their MicroRNA Cargo: New Players in Peripheral Nerve Regeneration.
AB  - Peripheral nerve injury is a major clinical problem and often results in a poor
      functional recovery. Despite obvious clinical need, treatment strategies have
      been largely suboptimal. In the nervous system, exosomes, which are nanosized
      extracellular vesicles, play a critical role in mediating intercellular
      communication. More specifically, microRNA carried by exosomes are involved in
      various key processes such as nerve and vascular regeneration, and exosomes
      originating from Schwann cells, macrophages, and mesenchymal stem cells can
      promote peripheral nerve regeneration. In this review, the current knowledge of
      exosomes' and their miRNA cargo's role in peripheral nerve regeneration are
      summarized. The possible future roles of exosomes in therapy and the potential
      for microRNA-containing exosomes to treat peripheral nerve injuries are also
      discussed.

PMID- 30223742
TI  - Teaching-Learning Strategy for Promoting Student Success: Asynchronous Post-Exam
      Reflections.
AB  - Students who actively engage in reflection and receive guidance from faculty may
      assume accountability for learning and adjust study habits based on academic
      performance. The literature supports a need for nurse educators to develop theory
      based strategies to integrate reflection and meaningful feedback in large
      didactic courses. The author in this paper describes the use of King's goal
      attainment theory and debriefing best practice guidelines to develop an
      asynchronous post-exam reflection teaching-learning strategy to promote student
      success in an undergraduate nursing pathophysiology course. Incorporation of the
      reflections enabled the nurse educator to collaborate with each student, provide
      prompt and personalized feedback, and efficiently identify at-risk students.

PMID- 30223744
TI  - Nursing Science Quarterly Best Paper Award: 2017.

PMID- 30223743
TI  - Empowerment in Nursing Literature: An Update and Look to the Future.
AB  - This review was conducted to describe empowerment theories that have influenced
      nursing practice, education, and research. Multiple perspectives of empowerment
      including structural, psychological, and group have contributed to the failure to
      consistently describe and measure this complex concept. The majority of
      empowerment literature originates from nonnursing theoretical frameworks. This
      review suggests that the nursing theory of work team/group empowerment, a
      midlevel nursing theory based upon King's conceptual framework of nursing, may be
      used to better understand and improve nurses' work team's/group's empowerment
      within healthcare organizations.

PMID- 30223745
TI  - Mentoring: The Giving of Blessings.
AB  - The authors of this article present three theoretical models of mentoring
      informing nursing as well as other disciplines. How these models intersect to
      expand understanding of the evolution of the role of mentoring in nursing is
      discussed.

PMID- 30223746
TI  - More Thoughts About Conceptual Models and Literature Reviews: Focus on Population
      Health.
AB  - This essay extends discussion of the ways in which a conceptual model of nursing
      can guide literature reviews. Emphasis is placed on ways in which the conceptual
      model of nursing and population health was used to guide and/or categorize the
      results of scoping reviews of the literature. Examples are presented in the form
      of diagrams and narrative explanations of the resultant conceptual-theoretical
      empirical structures.

PMID- 30223747
TI  - Thinking of Being or Becoming a Leader: Lessons and Quotes.
AB  - The "actions" of the nurse theorists have shaped nursing as a discipline by
      providing distinct knowledge that serves as a guide for research, practice,
      education, and leadership. With these "actions," the theorists have "inspired"
      generations of nurses dedicated to excellence in nursing; the theorists were and
      are some of the original leaders in nursing. The purpose of this paper is to
      reflect on a personal leading-following path guided by Parse's humanbecoming
      paradigm, specifically her leading-following model.

PMID- 30223748
TI  - Using Simulation to Enhance Global Nursing.
AB  - In light of the technological, social, and political changes taking place in the
      world today, it is important that nurses are not just culturally competent but
      globally informed and engaged. The goal of this paper is to help nurses help
      their patients and themselves to benefit from globalization. The use of guided
      simulation, virtual reality, and augmented reality learning experiences is
      considered for each of five areas of global nursing; global aesthetics, global
      intelligence, global ethics, global politics, and global health. This approach
      invites nurses and student nurses to discern new patterns, take charge of their
      learning, and build multiple iterations to facilitate the processing of new and
      different information and "realities."

PMID- 30223749
TI  - Situational Awareness: A Leadership Phenomenon.

PMID- 30223750
TI  - Community Engagement: Transformation for Health Framework.
AB  - The dialogue with Dr. Christine Esperat is about her project working with people
      in the community to establish transformation. She shares her vision and the
      process of developing a community-based health program.

PMID- 30223751
TI  - The Ethics of Scholarship With Social Media.
AB  - The use of social media by professional nurses is increasing at exponential
      rates. What are the possible nursing ethics involved as nurses utilize the
      various emerging digital electronic platforms? This article begins a discussion
      on the usage of social media and the responsibilities of nurse scholars who
      utilize social media platforms both personally and professionally. A
      humanbecoming paradigm perspective undergirds a discussion of ethical
      implications for future disciplinary scholar perspectives and position
      statements.

PMID- 30223752
TI  - Engaging With Persons to Transcend Patient Safety.
AB  - This article focuses on engaging with persons to transcend patient safety
      endeavors and improvement projects. Transcending patient safety involves a
      situational awareness and engaging to bring to the forefront the goals, dreams,
      and aspirations of those persons entrusted to nursing care.

PMID- 30223753
TI  - Communication and Technology: Ida Orlando's Theory Applied.
AB  - Today's bedside nurse communicates with patients in an environment that
      incorporates a wide variety of technology, from simple instruments such as a
      penlight to complex devices including cellphones, interactive computers, and
      computerized intravenous pumps. This is an excellent time to examine
      communication between the nurse and patient in today's fast-paced,
      technologically driven environment. Orlando's theory of the dynamic nurse-patient
      relationship provides a theoretical framework for understanding that
      communication. The proposed model affords a visual demonstration to assist in
      teaching communication.

PMID- 30223754
TI  - Technology and Teaching-Learning: Opportunities and Restrictions.
AB  - The author introduces a discussion by a nurse faculty of a teaching-learning
      strategy based on King's theory of goal attainment. Considering technology merely
      as a tool to be used in extending the traditional time-space boundaries of the
      classroom, the author challenges faculty to seek innovative ways of honoring the
      unique person of the student and illuminating pathways of discovery in the
      teaching-learning journey.

PMID- 30223755
TI  - Monograph Review: The NLN Jeffries Simulation Theory (2016), edited by Pamela R.
      Jeffries.

PMID- 30223756
TI  - Clinical Simulation: Controversies and Connections.

PMID- 30223757
TI  - Re-Envisioning Evidence Gap Maps With Qualitative Research.
AB  - Evidence gap maps (EGMs) are the concern of this column. A brief history of
      evidence summaries including literature and systematic reviews is presented
      followed by a discussion of the process of creating an evidence map. Then,
      concerns about a lack of inclusion of qualitative nursing research in particular
      are addressed.

PMID- 30223758
TI  - The Living Experience of Suffering: A Parse Method Study.
AB  - This study aimed to explore the phenomenon of suffering as viewed from the
      humanbecoming paradigm. The Parse research method was used for this study and
      answers the question: What is the structure of the living experience of
      suffering? The participants were 10 individuals who experienced one of the most
      dreadful typhoons in the archipelago of the Philippines. The central finding of
      the study was as follows: Suffering is penetrating disheartenment amid
      resoluteness, as pondering with diverse alliances surfaces with lingering
      glimmers of destruction. The findings are discussed in relation to the
      humanbecoming paradigm and related literature.

PMID- 30223759
TI  - Sociodemographic Factors Associated With Engagement in Diabetes Self-management
      Education Among People With Diabetes in the United States.
AB  - OBJECTIVE:: Research outside the United States shows that certain subgroups of
      patients (eg, those who are older, male, of low socioeconomic status, and
      uninsured) are less likely than others to report receiving diabetes self
      management education (DSME); however, less is known about DSME uptake in the
      United States. We examined sociodemographic, patient, and behavioral
      characteristics associated with DSME in a nationally representative sample.
      METHODS:: We analyzed data from the 2011-2013 Behavioral Risk Factor Surveillance
      System for 84 179 adults who self-identified receiving a diagnosis of diabetes.
      We constructed weighted, multivariate logistic regression models to examine the
      associations between DSME and sociodemographic characteristics (age, sex,
      race/ethnicity, marital status, education, and annual household income), patient
      characteristics (body mass index, having a regular provider, health insurance
      status, health status, and insulin use), and self-management behaviors (home foot
      examination, home blood glucose testing, and physical activity). RESULTS:: More
      than half (n = 45 557, 53.7% [weighted]) of respondents reported engaging in
      DSME. Compared with non-Hispanic white adults, non-Hispanic black adults were
      more likely to engage in DSME (adjusted odds ratio [aOR] = 1.17; 95% confidence
      interval [CI], 1.07-1.29). Respondents were less likely to engage in DSME if they
      were male (aOR = 0.85; 95% CI, 0.80-0.91) or Hispanic (aOR = 0.81; 95% CI, 0.71
      0.92), were a high school graduate (but no college; aOR = 0.71; 95% CI, 0.66
      0.78) or less than a high school graduate (aOR = 0.51; 95% CI, 0.45-0.59), had an
      annual household income of $15 000-$24 999 (aOR = 0.81; 95% CI, 0.73-0.89) or
      <$15 000 (aOR = 0.70; 95% CI, 0.62-0.78), or had no health insurance (aOR = 0.87;
      95% CI, 0.76-0.98). DSME was significantly associated with all 3 self-management
      behaviors. CONCLUSIONS:: Increasing public health interventions aimed at
      educating people with diabetes about self-management could improve outcomes.

PMID- 30223760
TI  - Disability Rating and 1-Year Mortality Among Veterans With Service-Connected
      Health Conditions.
AB  - OBJECTIVES:: Military service is associated with an increased risk of disability
      and death after discharge. This study determined the relationships among
      characteristics, disability ratings, and 1-year mortality risks of veterans
      receiving compensation for service-connected health conditions (ie, conditions
      related to illnesses or injuries incurred or aggravated during military service).
      METHODS:: This study included 4 010 720 living veterans who had >=1 service
      connected health condition and were receiving disability compensation on October
      1, 2016. We obtained data on veteran demographic, military service, and
      disability characteristics from the Veterans Benefits Administration VETSNET file
      and on 1-year mortality from the Veterans Administration vital status file. We
      compared veteran characteristics and 1-year mortality rates within and between
      the following combined service-connected disability rating categories: low, 10%
      to 40% disability; medium, 50% to 90% disability; high, 100% disability. We used
      logistic regression analysis to determine the relationships between disability
      ratings and 1-year mortality rates. RESULTS:: Of 4 010 720 veterans, 515 095
      (12.8%) had high disability ratings, 1 600 786 (39.9%) had medium disability
      ratings, and 1 894 839 (47.2%) had low disability ratings. The 1-year mortality
      rates were 4.5% for those with high disability, 1.9% for those with medium
      disability, and 1.9% for those with low disability ratings. Compared with
      veterans with low disability ratings, veterans with high disability ratings had
      more than twice the odds of 1-year mortality (odds ratio = 2.45; 95% confidence
      interval, 2.40-2.50). CONCLUSIONS:: The combined disability rating is an
      important determinant of short-term survival among veterans with service
      connected health conditions. Veterans with a 100% disability rating comprise a
      highly select group with increased short-term risk of death due at least in part
      to their military service. Future studies assessing the relationships among
      combat exposure, age, duration of disability, disability ratings, and survival
      would be valuable.

PMID- 30223761
TI  - The Impact of PCOS in the Offspring.

PMID- 30223762
TI  - Letter from the editor.

PMID- 30223763
TI  - Human Vaccines & Immunotherapeutics: News.

PMID- 30223764
TI  - Outcomes in Bilateral Vocal Fold Immobility: A Retrospective Cohort Analysis.
AB  - Objective To test the hypothesis that the etiologies of bilateral vocal fold
      mobility impairment (BLVFI), bilateral vocal fold paralysis (BVFP), and posterior
      glottis stenosis (PGS) have distinct clinical outcomes. To identify patient
      specific and procedural factors that influence tracheostomy-free survival. Study
      Design Retrospective cohort study. Setting Johns Hopkins Medical Center from 2004
      to 2015. Subjects and Methods Case series with chart review of 68 patients with
      PGS and 17 patients with BVFP. Multiple logistic regression analysis determined
      factors associated with airway prosthesis dependence at last follow-up and the
      procedural burden (defined as number of operative procedures per year). Results
      PGS comprised the majority of BLVFI (76%). PGS injury arose primarily after
      endotracheal intubation (91%), while BVFP most commonly was due to iatrogenic
      surgical injury to bilateral recurrent laryngeal nerves (88%, P < .001). Overall
      in BLVFI, 66% were tracheostomy free at last follow-up (62% in PGS, 82% in BVFP).
      Of those who underwent an operative intervention to be decannulated, 88% were
      decannulated (90% PGS, 80% BVFP). Patients with PGS required higher procedural
      burden to achieve decannulation compared with the BVFP cohort (3.1 +/- 5.2 vs
      0.71 +/- 1.4, P = .002). In multivariate analysis of PGS, smoking was a risk
      factor for tracheostomy dependence ( P = .026). Conclusions BLVFI is primarily an
      iatrogenic complication. There are high rates of tracheostomy dependence in
      BLVFI, with procedural intervention needed for decannulation. Compared with BVFP,
      patients with PGS had a higher procedural burden overall and to achieve
      decannulation. Patients with PGS should be counseled that smoking, a modifiable
      risk factor, may increase the risk of tracheostomy dependence.

PMID- 30223765
TI  - From the Fundamental Attribution Error to the Truly Fundamental Attribution Error
      and Beyond: My Research Journey.
AB  - This essay traces continuities and changes in focus of research and theory in my
      career. I describe early work on insensitivity to role-conferred advantages in
      self-presentation (and the personal experiences that prompted that work) and the
      subsequent identification and naming of the "fundamental attribution error." I
      next describe my work on the role that construal processes play in determining
      responses to various decision-making and attributional contexts. That work, in
      turn, culminated in identification and exploration of what I now deem the truly
      "fundamental attribution error": the illusion of superior personal objectivity
      and its various consequences for interpersonal and intergroup interactions. I
      conclude with the lessons I have drawn from my applied work on conflict
      resolution.

PMID- 30223766
TI  - Quantifying genomic connectedness and prediction accuracy from additive and non
      additive gene actions.
AB  - BACKGROUND: Genetic connectedness is classically used as an indication of the
      risk associated with breeding value comparisons across management units because
      genetic evaluations based on best linear unbiased prediction rely for their
      success on sufficient linkage among different units. In the whole-genome
      prediction era, the concept of genetic connectedness can be extended to measure a
      connectedness level between reference and validation sets. However, little is
      known regarding (1) the impact of non-additive gene action on genomic
      connectedness measures and (2) the relationship between the estimated level of
      connectedness and prediction accuracy in the presence of non-additive genetic
      variation. RESULTS: We evaluated the extent to which non-additive kernel
      relationship matrices increase measures of connectedness and investigated its
      relationship with prediction accuracy in the cross-validation framework using
      best linear unbiased prediction and coefficients of determination. Simulated data
      assuming additive, dominance, and epistatic gene action scenarios and real swine
      data were analyzed. We found that the joint use of additive and non-additive
      genomic kernel relationship matrices or non-parametric relationship matrices led
      to increased capturing of connectedness, up to 25%, and improved prediction
      accuracies compared to those of baseline additive relationship counterparts in
      the presence of non-additive gene action. CONCLUSIONS: Our findings showed that
      connectedness metrics can be extended to incorporate non-additive genetic
      variation of complex traits. Use of kernel relationship matrices designed to
      capture non-additive gene action increased measures of connectedness and improved
      whole-genome prediction accuracy, further broadening the scope of genomic
      connectedness studies.

PMID- 30223767
TI  - A document level neural model integrated domain knowledge for chemical-induced
      disease relations.
AB  - BACKGROUND: The effective combination of texts and knowledge may improve
      performances of natural language processing tasks. For the recognition of
      chemical-induced disease (CID) relations which may span sentence boundaries in an
      article, although existing CID systems explored the utilization for knowledge
      bases, the effects of different knowledge on the identification of a special CID
      haven't been distinguished by these systems. Moreover, systems based on neural
      network only constructed sentence or mention level models. RESULTS: In this work,
      we proposed an effective document level neural model integrated domain knowledge
      to extract CID relations from biomedical articles. Basic semantic information of
      an article with respect to a special CID candidate pair was learned from the
      document level sub-network module. Furthermore, knowledge attention depending on
      the representation of the article was proposed to distinguish the influences of
      different knowledge on the special CID pair and then the final representation of
      knowledge was formed by aggregating weighed knowledge. Finally, the integrated
      representations of texts and knowledge were passed to a softmax classifier to
      perform the CID recognition. Experimental results on the chemical-disease
      relation corpus proposed by BioCreative V show that our proposed system
      integrated knowledge achieves a good overall performance compared with other
      state-of-the-art systems. CONCLUSIONS: Experimental analyses demonstrate that the
      introduced attention mechanism on domain knowledge plays a significant role in
      distinguishing influences of different knowledge on the judgment for a special
      CID relation.

PMID- 30223768
TI  - Assessment of the performance of hidden Markov models for imputation in animal
      breeding.
AB  - BACKGROUND: In this paper, we review the performance of various hidden Markov
      model-based imputation methods in animal breeding populations. Traditionally,
      pedigree and heuristic-based imputation methods have been used for imputation in
      large animal populations due to their computational efficiency, scalability, and
      accuracy. Recent advances in the area of human genetics have increased the
      ability of probabilistic hidden Markov model methods to perform accurate phasing
      and imputation in large populations. These advances may enable these methods to
      be useful for routine use in large animal populations, particularly in
      populations where pedigree information is not readily available. METHODS: To test
      the performance of hidden Markov model-based imputation, we evaluated the
      accuracy and computational cost of several methods in a series of simulated
      populations and a real animal population without using a pedigree. First, we
      tested single-step (diploid) imputation, which performs both phasing and
      imputation. Second, we tested pre-phasing followed by haploid imputation.
      Overall, we used four available diploid imputation methods (fastPHASE, Beagle
      v4.0, IMPUTE2, and MaCH), three phasing methods, (SHAPEIT2, HAPI-UR, and Eagle2),
      and three haploid imputation methods (IMPUTE2, Beagle v4.1, and Minimac3).
      RESULTS: We found that performing pre-phasing and haploid imputation was faster
      and more accurate than diploid imputation. In particular, among all the methods
      tested, pre-phasing with Eagle2 or HAPI-UR and imputing with Minimac3 or IMPUTE2
      gave the highest accuracies with both simulated and real data. CONCLUSIONS: The
      results of this study suggest that hidden Markov model-based imputation
      algorithms are an accurate and computationally feasible approach for performing
      imputation without a pedigree when pre-phasing and haploid imputation are used.
      Of the algorithms tested, the combination of Eagle2 and Minimac3 gave the highest
      accuracy across the simulated and real datasets.

PMID- 30223769
TI  - Systematic evaluation of signal-to-noise ratio in variant detection from single
      cell genome multiple displacement amplification and exome sequencing.
AB  - BACKGROUND: The current literature on single cell genomic analyses on the DNA
      level is conflicting regarding requirements for cell quality, amplification
      success rates, allelic dropouts and resolution, lacking a systematic comparison
      of multiple cell input down to the single cell. We hypothesized that such a
      correlation assay would provide an approach to address the latter issues,
      utilizing the leukemic cell line OCI-AML3 with a known set of genetic
      aberrations. RESULTS: By analyzing single and multiple cell replicates (2 to 50
      cells) purified by micromanipulation and serial dilution we stringently assessed
      the signal-to-noise ratio (SNR) from single as well as a discrete number of cells
      based on a multiple displacement amplification method, with whole exome
      sequencing as signal readout. In this setting, known OCI-AML3 mutations as well
      as large copy number alterations could be identified, adding to the current
      knowledge of cytogenetic status. The presence of DNMT3A R882C, NPM1 W288 fs and
      NRAS Q61L was consistent, in spite of uneven allelic read depths. In contrast, at
      the level of single cells, we observed that one-third to half of all variants
      were not reproduced in the replicate sample, and this allelic mismatch displayed
      an exponential function of cell input. Large signature duplications were
      discernible from 5 cells, whereas deletions were visible down to the single cell.
      Thus, even under highly optimized conditions, single cell whole genome
      amplification and interpretation must be taken with considerable caution, given
      that allelic change is frequent and displays low SNR. Allelic noise is rapidly
      alleviated with increased cell input, and the SNR is doubled from 2 to 50 cells.
      CONCLUSIONS: In conclusion, we demonstrate noisy allele distributions, when
      analyzing genetic aberrations within single cells relative to multiple cells.
      Based on the presented data we recommend that single cell analyses should include
      replicate cell dilution assays for a given setup for relative assessment of
      procedure-specific SNR to ensure that the resolution supports the specific
      hypotheses.

PMID- 30223770
TI  - Comparative metabolomics reveals the metabolic variations between two endangered
      Taxus species (T. fuana and T. yunnanensis) in the Himalayas.
AB  - BACKGROUND: Plants of the genus Taxus have attracted much attention owing to the
      natural product taxol, a successful anti-cancer drug. T. fuana and T. yunnanensis
      are two endangered Taxus species mainly distributed in the Himalayas. In our
      study, an untargeted metabolomics approach integrated with a targeted UPLC-MS/MS
      method was applied to examine the metabolic variations between these two Taxus
      species growing in different environments. RESULTS: The level of taxol in T.
      yunnanensis is much higher than that in T. fuana, indicating a higher economic
      value of T. yunnanensis for taxol production. A series of specific metabolites,
      including precursors, intermediates, competitors of taxol, were identified. All
      the identified intermediates are predominantly accumulated in T. yunnanensis than
      T. fuana, giving a reasonable explanation for the higher accumulation of taxol in
      T. yunnanensis. Taxusin and its analogues are highly accumulated in T. fuana,
      which may consume limited intermediates and block the metabolic flow towards
      taxol. The contents of total flavonoids and a majority of tested individual
      flavonoids are significantly accumulated in T. fuana than T. yunnanensis,
      indicating a stronger environmental adaptiveness of T. fuana. CONCLUSIONS:
      Systemic metabolic profiling may provide valuable information for the
      comprehensive industrial utilization of the germplasm resources of these two
      endangered Taxus species growing in different environments.

PMID- 30223771
TI  - Diagnostic test accuracy of a novel smartphone application for the assessment of
      attention deficits in delirium in older hospitalised patients: a prospective
      cohort study protocol.
AB  - BACKGROUND: Delirium is a common and serious clinical syndrome which is often
      missed in routine clinical care. The core cognitive feature is inattention. We
      developed a novel bedside neuropsychological test for assessing inattention in
      delirium implemented on a smartphone platform (DelApp). We aim to evaluate the
      diagnostic performance of the DelApp in a representative cohort of older
      hospitalised patients. METHODS: This is a prospective study of older non
      scheduled hospitalised patients (target n = 500, age >= 65), recruited from
      elderly care and acute orthopaedic wards. Exclusion criteria are: non-English
      speakers; severe vision or hearing impairment; photosensitive epilepsy. A
      structured reference standard delirium assessment based on DSM-5 criteria will be
      used, which includes a cognitive test battery administered by a trained assessor
      (Orientation-Memory-Concentration Test, Abbreviated Mental Test-10, Delirium
      Rating Severity Scale-Revised-98, digit span, months and days backwards,
      Vigilance A' test) and assessment of arousal (Observational Scale of Level of
      Arousal, Richmond Agitation Sedation Scale). Prior change in cognition will be
      documented using the Informant Questionnaire on Cognitive Decline in the Elderly.
      Patients will be categorized as delirium (with/without dementia), possible
      delirium, dementia, no cognitive impairment, or undetermined. A separate assessor
      (blinded to diagnosis and assessments) will administer the DelApp index test
      within 3 h of the reference standard assessment. The DelApp comprises assessment
      of arousal (score 0-4) and sustained attention (score 0-6), yielding a total
      score between 0 and 10 (higher score = better performance). Outcomes (length of
      stay, mortality and discharge location) will be collected at 12 weeks. We will
      evaluate a priori cutpoints derived from a previous case-control study. Measures
      of the accuracy of DelApp will include sensitivity, specificity, positive and
      negative predictive values, and area under the ROC curve. We plan repeat
      assessments on up to 4 occasions in a purposive subsample of 30 patients (15
      delirium, 15 no delirium) to examine changes over time. DISCUSSION: This study
      evaluates the diagnostic test accuracy of a novel smartphone test for delirium in
      a representative cohort of older hospitalised patients, including those with
      dementia. DelApp has the potential to be a convenient, objective method of
      improving delirium assessment for older people in acute care. TRIAL REGISTRATION:
      Clinical trials.gov, NCT02590796 . Registered on 29 Oct 2015. Protocol version 5,
      dated 25 July 2016.

PMID- 30223772
TI  - Exploring bacterial growth and recolonization after preoperative hand
      disinfection and surgery between operating room nurses and non-health care
      workers: a pilot study.
AB  - BACKGROUND: To prevent cross infection the surgical team perform preoperative
      hand disinfection before dressed in surgical gowns and gloves. Preoperative hand
      disinfection does not make hands sterile and the surgical glove cuff end has been
      regarded as a weak link, since it is not a liquid-proof interface. The aims were
      to investigate if there were differences in bacterial growth and recolonization
      of hands between operating room nurses and non-health care workers as well as to
      investigate if bacterial growth existed at the surgical glove cuff end during
      surgery. METHODS: This pilot project was conducted as an exploratory comparative
      clinical trial. Bacterial cultures were taken from the glove and gown interface
      and at three sites of the hands of 12 operating room nurses and 13 non-health
      care workers controls directly after preoperative hand disinfection and again
      after wearing surgical gloves and gowns. Colony forming units were analysed with
      Mann-Whitney U test and Wilcoxon Sign Ranks test comparing repeated measurements.
      Categorical variables were evaluated with chi-square test or Fisher's exact test.
      RESULTS: Operating room nurses compared to non-health care workers had
      significant higher bacterial growth at two of three culture sites after surgical
      hand disinfection. Both groups had higher recolonization at one of the three
      culture sites after wearing surgical gloves. There were no differences between
      the groups in total colony forming units, that is, all sampling sites. Five out
      of 12 of the operating room nurses had bacterial growth at the glove cuff end and
      of those, four had the same bacteria at the glove cuff end as found in the
      cultures from the hands. Bacteria isolated from the glove cuff were P. acnes, S.
      warneri, S. epidermidis and Micrococcus species, the CFU/mL ranged from 10 to 40.
      CONCLUSIONS: There were differences in bacterial growth and re-colonization
      between the groups but this was inconclusive. However, bacterial growth exists at
      the glove cuff and gown interface, further investigation in larger study is
      needed, to build on these promising, but preliminary, findings. TRIAL
      REGISTRATION: Trial registration was performed prospectively at Research web (FOU
      in Sweden, 117,971) 14/01/2013, and retrospectively at ClinicalTrials.gov (
      NCT02359708 ). 01/27/2015.

PMID- 30223773
TI  - A method for addressing right upper lobe obstruction with right-sided double
      lumen endobronchial tubes during surgery: a randomized controlled trial.
AB  - BACKGROUND: A right-sided double-lumen tube (R-DLT) tends to obstruct the right
      upper lobe intraoperatively due to anatomical distortion during surgery. If the R
      DLT is poorly matched with the patient's airway anatomy, it will not be possible
      to correctly replace the tube with a fiberoptic bronchoscope (FOB). In our study,
      we aimed to explore an efficient method for difficult repositioning caused by
      right upper lobe occlusion during surgery: repositioning the R-DLT from the right
      main bronchus into the left main bronchus. The current study was designed to
      assess the efficacy and safety of this method. METHODS: Sixty adult patients
      scheduled to undergo left-sided thoracic surgery were randomly assigned to two
      groups. With the patient in the right lateral position during surgery, the R-DLT
      was pulled back to the trachea while being rotated 90 degrees  clockwise; it was
      then either rotated 90 degrees  clockwise for placement into the left main
      bronchus (Group L) or rotated 90 degrees  anticlockwise and returned to the right
      main bronchus (Group R) using FOB guidance. The primary outcomes included
      clinical performance, which was measured by intubation time, and the quality of
      lung collapse. A secondary outcome was safety, which was determined according to
      bronchial injury and vocal cord injury. RESULTS: The median intubation time (IQR
      [range]) required for placement of a R-DLT into the left main bronchus was
      shorter than the time required for placement into the right main bronchus (15.0 s
      [IQR, 12.0 to 20.0 s]) vs 23.5 s [IQR, 14.5 to 65.8 s], P = 0.005). The groups
      showed comparable overall results for the quality of lung collapse during the
      total period of one-lung ventilation (P = 1.000). The numbers of patients with
      bronchial injuries or vocal cord injuries were also comparable between groups
      (Group R, 11/30 vs. Group L 8/30, P = 0.580 for bronchus injuries; Group R, 15/30
      vs. Group L 13/30, P = 0.796 for vocal cord injuries). CONCLUSIONS: Repositioning
      a R-DLT from the right main bronchus into the left main bronchus had good
      clinical performance without causing additional injury. This may be an efficient
      method for the difficult repositioning of a R-DLT due to right upper lobe
      occlusion during surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry,
      ChiCTR-IPR-15006933 , registered on 15 August 2015.

PMID- 30223774
TI  - Molecular genetic and biochemical evidence for adaptive evolution of leaf abaxial
      epicuticular wax crystals in the genus Lithocarpus (Fagaceae).
AB  - BACKGROUND: Leaf epicuticular wax is an important functional trait for
      physiological regulation and pathogen defense. This study tests how selective
      pressure may have forced the trait of leaf abaxial epicuticular wax crystals
      (LAEWC) and whether the presence/absence of LAEWC is associated with other
      ecophysiological traits. Scanning Electron Microscopy was conducted to check for
      LAEWC in different Lithocarpus species. Four wax biosynthesis related genes,
      including two wax backbone genes ECERIFERUM 1 (CER1) and CER3, one regulatory
      gene CER7 and one transport gene CER5, were cloned and sequenced.
      Ecophysiological measurements of secondary metabolites, photosynthesis, water
      usage efficiency, and nutrition indices were also determined. Evolutionary
      hypotheses of leaf wax character transition associated with the evolution of
      those ecophysiological traits as well as species evolution were tested by maximum
      likelihood. RESULTS: Eight of 14 studied Lithocarpus species have obvious LAEWC
      appearing with various types of trichomes. Measurements of ecophysiological
      traits show no direct correlations with the presence/absence of LAEWC. However,
      the content of phenolic acids is significantly associated with the gene evolution
      of the wax biosynthetic backbone gene CER1, which was detected to be positively
      selected when LAEWC was gained during the late-Miocene-to-Pliocene period.
      CONCLUSIONS: Changes of landmass and vegetation type accelerated the
      diversification of tropical and subtropical forest trees and certain herbivores
      during the late Miocene. As phenolic acids were long thought to be associated
      with defense against herbivories, co-occurrence of LAEWC and phenolic acids may
      suggest that LAEWC might be an adaptive defensive mechanism in Lithocarpus.

PMID- 30223775
TI  - Disseminated extrapulmonary Legionella pneumophila infection presenting with
      panniculitis: case report and literature review.
AB  - BACKGROUND: Legionellosis is a well-known cause of pneumonia. Primary cutaneous
      and subcutaneous infection caused by Legionella pneumophila is rare and the
      diagnosis is challenging. CASE PRESENTATION: A 38-year-old Thai woman with
      systemic lupus erythematosus and myasthenia gravis treated with prednisolone and
      azathioprine presented to our hospital with low-grade fever, diarrhea, and
      indurated skin lesions on both thighs. Initial examination showed plaques on both
      inner thighs. Magnetic resonance imaging showed myositis and swelling of the skin
      and subcutaneous tissue. Diagnosis of panniculitis due to L. pneumophila was
      carried out by histopathology, Gram stain, and 16S rRNA gene sequencing method of
      tissue biopsy from multiple sites on both thighs. Myocarditis was diagnosed by
      echocardiography. The final diagnosis was disseminated extrapulmonary
      legionellosis. Treatment comprised intravenous azithromycin for 3 weeks and the
      skin lesions, myositis and myocarditis resolved. Oral azithromycin and
      ciprofloxacin were continued for 3 months to ensure eradication of the organism.
      The patient's overall condition improved. CONCLUSIONS: To our knowledge, we
      report the first case of L. pneumophila infection manifesting with panniculitis,
      possible myositis, and myocarditis in the absence of pneumonia. The diagnosis of
      extrapulmonary Legionella infection is difficult, especially in the absence of
      pneumonia. A high index of suspicion and appropriate culture with special media
      or molecular testing are required. Initiation of appropriate treatment is
      critical because delaying therapy was associated with progressive infection in
      our patient.

PMID- 30223776
TI  - Bivariate genome-wide association analysis strengthens the role of bitter
      receptor clusters on chromosomes 7 and 12 in human bitter taste.
AB  - BACKGROUND: Human perception of bitter substances is partially genetically
      determined. Previously we discovered a single nucleotide polymorphism (SNP)
      within the cluster of bitter taste receptor genes on chromosome 12 that accounts
      for 5.8% of the variance in the perceived intensity rating of quinine, and we
      strengthened the classic association between TAS2R38 genotype and the bitterness
      of propylthiouracil (PROP). Here we performed a genome-wide association study
      (GWAS) using a 40% larger sample (n = 1999) together with a bivariate approach to
      detect previously unidentified common variants with small effects on bitter
      perception. RESULTS: We identified two signals, both with small effects (< 2%),
      within the bitter taste receptor clusters on chromosomes 7 and 12, which
      influence the perceived bitterness of denatonium benzoate and sucrose octaacetate
      respectively. We also provided the first independent replication for an
      association of caffeine bitterness on chromosome 12. Furthermore, we provided
      evidence for pleiotropic effects on quinine, caffeine, sucrose octaacetate and
      denatonium benzoate for the three SNPs on chromosome 12 and the functional
      importance of the SNPs for denatonium benzoate bitterness. CONCLUSIONS: These
      findings provide new insights into the genetic architecture of bitter taste and
      offer a useful starting point for determining the biological pathways linking
      perception of bitter substances.

PMID- 30223778
TI  - Novel PNPLA2 gene mutation in a child causing neutral lipid storage disease with
      myopathy.
AB  - BACKGROUND: PNPLA2 gene mutations cause neutral lipid storage disease with
      myopathy (NLSD-M) or cardiomyopathies. The clinical phenotype, blood test
      results, imaging examination and gene analysis can be used to improve the
      understanding of NLSD-M, reduce the misdiagnosis rate and prevent physical
      disability and even premature death. CASE PRESENTATION: We report a Chinese child
      with NLSD-M presenting with marked asymmetric skeletal myopathy and hypertrophic
      cardiomyopathy. Blood biochemical tests revealed increased creatine kinase
      levels, and echocardiography revealed a diffuse and thick left ventricular wall.
      Gene analysis revealed a homozygous mutation c.155C > G (p.Thr52Arg) in PNPLA2.
      CONCLUSIONS: An understanding of the characteristic features is essential for the
      early diagnosis of NLSD-M. Our data expand the allelic spectrum of PNPLA2
      mutations, providing further evidence for genetic and clinical NLSD-M
      heterogeneity in younger individuals.

PMID- 30223779
TI  - Supporting healthful lifestyles during pregnancy: a health coach intervention
      pilot study.
AB  - BACKGROUND: Excessive gestational weight gain (GWG) is associated with adverse
      health outcomes in both the mother and child. Many previous lifestyle
      interventions in women with excess weight during pregnancy encouraging
      appropriate GWG have been unsuccessful, and there remains no consensus about the
      content, format, or theoretical framework of GWG interventions. We assessed the
      feasibility and acceptability of a remote health coach intervention to promote
      healthful lifestyle behaviors and appropriate GWG among overweight pregnant
      women. METHODS: At one northeastern US clinic, we enrolled 30 overweight (pre
      pregnancy BMI >= 25 kg/m2) pregnant women at a median gestation of 12.5 weeks
      (IQR: 11-15) into a one-arm trial. We connected participants with a health coach
      to provide behavioral support to help participants adopt healthful lifestyles
      during pregnancy. Health coaches contacted participants by phone every 2-3 weeks
      to monitor goals, and sent emails and text messages between calls. Participants
      completed baseline (N = 30) and follow-up (N = 26) surveys at the end of the
      intervention (36 weeks gestation), as well as follow-up phone interviews (N =
      18). RESULTS: Among 30 participants, median age was 32 years (IQR: 28-33), median
      self-reported pre-pregnancy BMI was 27.3 kg/m2 (IQR: 25.7-31.1), and 17/30 were
      white, 9/30 African-American, and 3/30 Asian. Three-quarters (22/29) of
      participants completed at least a college degree. Although 25/30 participants
      reported in baseline surveys that they worried about being able to lose the
      weight postpartum that they expected to gain during pregnancy, just 12/26
      participants reported the same at follow-up (P < 0.001). In follow-up surveys,
      21/26 participants reported that health coaches were helpful in keeping them
      motivated, and 22/26 thought the phone conversations helped them face problems
      and find solutions. Based on qualitative assessment, several themes emerged in
      follow-up interviews about the quality of the intervention including
      accountability and support from health coaches. Participants also expressed
      desire for more visual resources and integration with standard clinical care to
      improve the intervention. CONCLUSIONS: We demonstrated feasibility and high
      participant satisfaction with our remote health coach intervention during
      pregnancy. We identified areas in which we could refine the intervention for
      inclusion in a full-scale RCT, such as integration with clinical care and
      additional visual resources. TRIAL REGISTRATION: Retrospectively registered at
      ClinicalTrials.gov ( NCT03080064 , 3/14/2017).

PMID- 30223777
TI  - ChIP-Seq reveals that QsMYB1 directly targets genes involved in lignin and
      suberin biosynthesis pathways in cork oak (Quercus suber).
AB  - BACKGROUND: Gene activity is largely controlled by transcriptional regulation
      through the action of transcription factors and other regulators. QsMYB1 is a
      member of the R2R3-MYB transcription factor family related to secondary growth,
      and in particular, with the cork development process. In order to identify the
      putative gene targets of QsMYB1 across the cork oak genome we developed a ChIP
      Seq strategy. RESULTS: Results provide direct evidence that QsMY1B targets genes
      encoding for enzymes involved in the lignin and suberin pathways as well as gene
      encoding for ABCG transporters and LTPs implicated in the transport of monomeric
      suberin units across the cellular membrane. These results highlight the role of
      QsMYB1 as a regulator of lignin and suberin biosynthesis, transport and assembly.
      CONCLUSION: To our knowledge, this work constitutes the first ChIP-Seq experiment
      performed in cork oak, a non-model plant species with a long-life cycle, and
      these results will contribute to deepen the knowledge about the molecular
      mechanisms of cork formation and differentiation.

PMID- 30223780
TI  - Factors influencing decision-making for caesarean section in Sweden - a
      qualitative study.
AB  - BACKGROUND: Rising rates of caesarean section (CS) are a concern in many
      countries, yet Sweden has managed to maintain low CS rates. Exploring the
      multifactorial and complex reasons behind the rising trend in CS has become an
      important goal for health professionals. The aim of the study was to explore
      Swedish obstetricians' and midwives' perceptions of the factors influencing
      decision-making for CS in nulliparous women in Sweden. METHODS: A qualitative
      design was chosen to gain in-depth understanding of the factors influencing the
      decision-making process for CS. Purposive sampling was used to select the
      participants. Four audio-recorded focus group interviews (FGIs), using an
      interview guide with open ended questions, were conducted with eleven midwives
      and five obstetricians from two selected Swedish maternity hospitals after
      obtaining written consent from each participant. Data were managed using NVivo(c)
      and thematically analysed. Ethical approval was granted by Trinity College
      Dublin. RESULTS: The thematic analysis resulted in three main themes; 'Belief in
      normal birth - a cultural perspective'; 'Clarity and consistency - a system
      perspective' and 'Obstetrician makes the final decision, but...', and each theme
      contained a number of subthemes. However, 'Belief in normal birth' emerged as the
      core central theme, overarching the other two themes. CONCLUSION: Findings
      suggest that believing that normal birth offers women and babies the best
      possible outcome contributes to having and maintaining a low CS rate. Both
      midwives and obstetricians agreed that having a shared belief (in normal birth),
      a common goal (of achieving normal birth) and providing mainly midwife-led care
      within a 'team approach' helped them achieve their goal and keep their CS rate
      low.

PMID- 30223781
TI  - Correlation between CTLA-4 and CD40 gene polymorphisms and their interaction in
      graves' disease in a Chinese Han population.
AB  - BACKGROUND: Single-nucleotide polymorphism (SNP) haplotype and SNP-SNP
      interactions of CTLA-4 and CD40 genes, with susceptibility to Graves' disease
      (GD), were explored in a Chinese Han population. METHODS: SNP were genotyped by
      high resolution melting (HRM). Use the method of Pearson chi2 test and Logistic
      regression for the association between single SNP and Graves' disease. Using the
      method of chi2 test and Multifactor Dimensionality Reduction (MDR) to analysis
      the haplotype frequency distribution, the interaction of SNPs respectively.
      RESULTS: Genotypic and allelic frequencies of SNP rs231775, rs3087243 and
      rs1883832 were statistically different between controls and GD (p < 0.05). Mutant
      allelic frequency of G rs231775 was higher, and A and T allelic frequencies of
      rs3087243 and rs1883832 were lower in GD than in controls (P < 0.05). In CTLA-4
      rs1024161, rs5742909, rs231775, rs231777, rs231779, rs3087243 and rs11571319
      showed D' < 50% and r2 < 0.3 among each SNP. We identified six commonly found
      haplotypes; TCGCTGC was associated with the highest GD risk (OR = 2.565) and
      TCACTAC the lowest (OR = 0.096). MDR analysis indicated interactions among the
      rs231775 GG, rs231779 TT and rs3087243 GG genotypes in CTLA-4 might increase GD
      risk by 2.53-fold (OR = 2.53). CONCLUSION: CTLA-4 and CD40 were associated with
      GD incidence in a Chinese Han population. The TCGCTGC and TCACTAC haplotypes in
      the CTLA-4 gene, were risk and protective factors for Graves'disease
      respectively. Interactions among the SNPs of rs231775, rs231779 and rs3087243
      significantly increase the susceptibility to GD.

PMID- 30223782
TI  - Successful reuse of a transplanted kidney 9 years after initial transplantation:
      4-year follow-up.
AB  - BACKGROUND: Kidney transplantation is the preferred renal replacement therapy for
      patients with end-stage renal disease, but the waiting list for kidneys continues
      to grow because of a shortage of donor organs. The reuse of transplanted kidneys
      would seem to be a good approach to expand the pool of available organs. Here, we
      describe the reuse of a kidney 9 years after the initial transplantation. At 4
      year follow-up, the second recipient is showing good renal function. CASE
      PRESENTATION: In 2005, a kidney was transplanted from a 40-year-old man, who
      suffered brain death due to an intracranial hemorrhage, into a 45-year-old man.
      Nine years later, the recipient suffered a ruptured cerebral aneurysm, resulting
      in brain death. The kidney was re-transplanted into a 40-year-old man with
      diabetic nephropathy who had received hemodialysis for 5 years. During 4 years of
      follow-up, the graft has functioned well. CONCLUSIONS: This case demonstrates the
      successful regrafting of a transplanted kidney. We believe this is the longest
      period for reuse of kidney after initial transplantation. The outcome suggests
      that a well-functioning transplanted kidney can be reused years after
      transplantation.

PMID- 30223783
TI  - Using different anthropometric indices to assess prediction ability of type 2
      diabetes in elderly population: a 5 year prospective study.
AB  - BACKGROUND: Emerging studies have investigated the association between different
      anthropometric indices with diabetes risk but the results were inconsistent. The
      aims of the study were to examine the associations of different anthropometric
      indices with incident diabetes risk and whether novel anthropometric indices
      improve diabetes prediction beyond traditional indices among elderly Chinese.
      METHODS: Nine thousand nine hundred sixty-two elderly individuals (age >= 60
      years old) derived from the prospective Dongfeng-Tongji cohort were included.
      Hazard ratio (HR) and corresponding 95% confidence interval (CI) were evaluated
      by Cox proportional hazard model to examine the associations between traditional
      anthropometric indices (body mass index [BMI], waist circumference [WC], waist-to
      height ratio [WHtR]), novel anthropometric indices (visceral adiposity index
      [VAI], a body shape index [ABSI], body roundness index [BRI]) and diabetes risk.
      Receiver operating characteristic (ROC) curve and area under curve (AUC) were
      applied to compare the novel anthropometric indices with the traditional indices
      in diabetes prediction. RESULTS: During mean 4.6 years of follow-up, 614 incident
      cases of type 2 diabetes (T2D) were identified. Significant positive associations
      were detected between BMI, WC, WHtR, VAI and BRI and incident T2D risk. For ABSI,
      no significant association was observed in either men or women. BMI was the
      strongest predictor in diabetes in men (AUC = 0.655) comparable with the other
      anthropometric indices (P < 0.05). Similar as men, BMI was the strongest
      predictor (AUC = 0.635) in women. Except for WC, the AUC of BMI was larger than
      WHtR, VAI, and BRI. In contrast, ABSI was not a good predictor in either men (AUC
      = 0.507) or women (AUC = 0.503). CONCLUSIONS: In elderly Chinese, BMI, WC, WHtR,
      VAI and BRI were positively associated with incident T2D risk. Among them, BMI
      was the strongest predictor in both men and women.

PMID- 30223784
TI  - Deleterious effects of dialysis emergency start, insights from the French REIN
      registry.
AB  - BACKGROUND: Emergency start (ES) of dialysis has been associated with worse
      outcome, but remains poorly documented. This study aims to compare the profile
      and outcome of a large cohort of patients starting dialysis as an emergency or as
      a planned step in France. METHODS: Data on all patients aged 18 years or older
      who started dialysis in mainland France in 2012 or in 2006 were collected from
      the Renal Epidemiology and Information Network and compared, depending on the
      dialysis initiation condition: ES or Planned Start (PS). ES was defined as a
      first dialysis within 24 h after a nephrology visit due to a life-threatening
      event. Three-year survival were compared, and a multivariate model was performed
      after multiple imputation of missing data, to determine the parameters
      independently associated with three-year survival. RESULTS: In 2012, 30.3% of all
      included patients (n = 8839) had ES. Comorbidities were more frequent in the ES
      than PS group (>= 2 cardiovascular diseases: 39.2% vs 28.8%, p < 0.001). ES was
      independently associated with worse three-year survival (57% vs. 68.2%, p =
      0.029, HR 1.10, 95% CI 1.01-1.19) in multivariate analysis. Among ES group, a
      large part had a consistent previous follow-up: 36.4% of them had >=3 nephrology
      consultations in the previous year. This subgroup of patients had a particularly
      high comorbidity burden. ES rate was stable between 2006 and 2012, but some
      proactive regions succeeded in reducing markedly the ES rate. CONCLUSION: ES
      remains frequent and is independently associated with worse three-year survival,
      demonstrating that ES deleterious impact is never overcome. This study shows that
      a large part of patients with ES had a previous follow-up, but high comorbidity
      burden that could favor acute decompensation with life-threatening conditions
      before uremic symptoms appearance. This suggests the need of closer end-stage
      renal disease follow-up or early dialysis initiation in these high-risk patients.

PMID- 30223785
TI  - Appropriate duration of post-surgical intravenous antibiotic therapy for pyogenic
      spondylodiscitis.
AB  - BACKGROUND: Most guidelines recommend 6 to 12 weeks of parenteral antibiotic
      treatment for pyogenic spondylodiscitis. When surgical debridement is adequately
      performed, further intravenous antibiotic treatment duration can be reduced than
      that of conservative treatment alone theoretically. However, the appropriate
      duration of post-surgical parenteral antibiotic treatment is still unknown. This
      study aimed to identify the risk factors of recurrence and evaluate the
      appropriate duration after surgical intervention. METHODS: This 3-year
      retrospective review included 102 consecutive patients who were diagnosed with
      pyogenic spondylodiscitis and underwent surgical intervention. Recurrence was
      defined as recurrent signs and symptoms and the need for another unplanned
      parenteral antibiotic treatment or operation within one year. This study included
      two major portions. First, independent risk factors for recurrence were
      identified by multivariable analysis, using the database of demographic
      information, pre-operative clinical signs and symptoms, underlying illness,
      radiographic findings, laboratory tests, intraoperative culture results, and
      treatment. Patients with any one of the risk factors were considered high-risk;
      those with no risk factors were considered low-risk. Recurrence rates after short
      term (<=3 weeks) and long-term (> 3 weeks) parenteral antibiotic treatment were
      compared between the groups. RESULTS: Positive blood culture and paraspinal
      abscesses were identified as independent risk factors of recurrence. Accordingly,
      59 (57.8%) patients were classified as low-risk and 43 (42.2%) as high-risk.
      Among the high-risk patients, a significantly higher recurrence rate occurred
      with short-term than with long-term antibiotic therapy (56.2% vs. 22.2%, p =
      0.027). For the low-risk patients, there was no significant difference between
      short-term and long-term antibiotic therapy (16.0% vs. 20.6%, p = 0.461).
      CONCLUSIONS: The appropriate duration of parenteral antibiotic treatment in
      patients with pyogenic spondylodiscitis after surgical intervention could be
      guided by the risk factors. The duration of postoperative intravenous antibiotic
      therapy could be reduced to 3 weeks for patients without positive blood culture
      or abscess formation.

PMID- 30223786
TI  - Apparent diffusion coefficient as an effective index for the therapeutic
      efficiency of brain chemoradiotherapy for brain metastases from lung cancer.
AB  - BACKGROUND: The potential of apparent diffusion coefficient (ADC) value
      alteration before and after chemoradiotherapy as a potential monitor for
      therapeutic efficiency of treatment for brain metastases from lung cancer were
      discussed. METHOD: Thirty lung cancer patients with brain metastases,
      conventional magnetic resonance imaging (MRI) examination and diffusion weighted
      imaging (DWI) were performed one week before chemoradiotherapy and after one
      treatment cycle and two treatment cycles. 43 tumor lesions were divided into
      effective group and invalid group according to the changes of the tumor size. The
      differences in ADC values at different time points before and after treatment in
      each treatment group were analyzed. RESULT: The maximum diameter of the tumor was
      no difference after one treatment cycle, but decreased after two treatment
      cycles. ADC values significantly increased after both one and two treatment
      cycles. In effective group, the ADC values were significantly increased after one
      and two treatment cycles. While, there are no difference in invalid group after
      one treatment cycle but decreased after two treatment cycles. DeltaADC values in
      effective group after one and two treatment cycles were both significantly higher
      than those in the invalid group. ROC curve analysis then revealed that the area
      under the curve (AUC) of DeltaADC after one treatment was 0.872. CONCLUSION: ADC
      values in brain metastases from lung cancer can help monitor and dynamically
      observe the therapeutic efficiency of whole brain chemoradiotherapy.

PMID- 30223787
TI  - Data-driven human transcriptomic modules determined by independent component
      analysis.
AB  - BACKGROUND: Analyzing the human transcriptome is crucial in advancing precision
      medicine, and the plethora of over half a million human microarray samples in the
      Gene Expression Omnibus (GEO) has enabled us to better characterize biological
      processes at the molecular level. However, transcriptomic analysis is challenging
      because the data is inherently noisy and high-dimensional. Gene set analysis is
      currently widely used to alleviate the issue of high dimensionality, but the user
      defined choice of gene sets can introduce biasness in results. In this paper, we
      advocate the use of a fixed set of transcriptomic modules for such analysis. We
      apply independent component analysis to the large collection of microarray data
      in GEO in order to discover reproducible transcriptomic modules that can be used
      as features for machine learning. We evaluate the usability of these modules
      across six studies, and demonstrate (1) their usage as features for sample
      classification, and also their robustness in dealing with small training sets,
      (2) their regularization of data when clustering samples and (3) the biological
      relevancy of differentially expressed features. RESULTS: We identified 139
      reproducible transcriptomic modules, which we term fundamental components (FCs).
      In studies with less than 50 samples, FC-space classification model outperformed
      their gene-space counterparts, with higher sensitivity (p < 0.01). The models
      also had higher accuracy and negative predictive value (p < 0.01) for small data
      sets (less than 30 samples). Additionally, we observed a reduction in batch
      effects when data is clustered in the FC-space. Finally, we found that
      differentially expressed FCs mapped to GO terms that were also identified via
      traditional gene-based approaches. CONCLUSIONS: The 139 FCs provide biologically
      relevant summarization of transcriptomic data, and their performance in low
      sample settings suggest that they should be employed in such studies in order to
      harness the data efficiently.

PMID- 30223789
TI  - Association mapping by aerial drone reveals 213 genetic associations for Sorghum
      bicolor biomass traits under drought.
AB  - BACKGROUND: Sorghum bicolor is the fifth most commonly grown cereal worldwide and
      is remarkable for its drought and abiotic stress tolerance. For these reasons and
      the large size of biomass varieties, it has been proposed as a bioenergy crop.
      However, little is known about the genes underlying sorghum's abiotic stress
      tolerance and biomass yield. RESULTS: To uncover the genetic basis of drought
      tolerance in sorghum at a genome-wide level, we undertook a high-density
      phenomics genome wide association study (GWAS) in which 648 diverse sorghum lines
      were phenotyped at two locations in California once per week by drone over the
      course of a growing season. Biomass, height, and leaf area were measured by drone
      for individual field plots, subjected to two drought treatments and a well
      watered control. The resulting dataset of ~ 171,000 phenotypic data-points was
      analyzed along with 183,989 genotype by sequence markers to reveal 213 high
      quality, replicated, and conserved GWAS associations. CONCLUSIONS: The genomic
      intervals defined by the associations include many strong candidate genes,
      including those encoding heat shock proteins, antifreeze proteins, and other
      domains recognized as important to plant stress responses. The markers identified
      by our study can be used for marker assisted selection for drought tolerance and
      biomass. In addition, our results are a significant step toward identifying
      specific sorghum genes controlling drought tolerance and biomass yield.

PMID- 30223788
TI  - DNA methylation of the promoter region of bnip3 and bnip3l genes induced by
      metabolic programming.
AB  - BACKGROUND: Environmental changes of biotic or abiotic nature during critical
      periods of early development may exert a profound influence on physiological
      functions later in life. This process, named developmental programming can also
      be driven through parental nutrition. At molecular level, epigenetic
      modifications are the most likely candidate for persistent modulation of genes
      expression in later life. RESULTS: In order to investigate epigenetic
      modifications induced by programming in rainbow trout, we focused on bnip3 and
      bnip3l paralogous genes known to be sensitive to environmental changes but also
      regulated by epigenetic modifications. Two specific stimuli were used: (i) early
      acute hypoxia applied at embryo stage and (ii) broodstock and fry methionine
      deficient diet, considering methionine as one of the main methyl-group donor
      needed for DNA methylation. We observed a programming effect of hypoxia with an
      increase of bnip3a and the four paralogs of bnip3l expression level in fry. In
      addition, parental methionine nutrition was correlated to bnip3a and bnip3lb1
      expression showing evidence for early fry programming. We highlighted that both
      stimuli modified DNA methylation levels at some specific loci of bnip3a and
      bnip3lb1. CONCLUSION: Overall, these data demonstrate that methionine level and
      hypoxia stimulus can be of critical importance in metabolic programming. Both
      stimuli affected DNA methylation of specific loci, among them, an interesting CpG
      site have been identified, namely - 884 bp site of bnip3a, and may be positively
      related with mRNA levels.

PMID- 30223791
TI  - Desmoid-type fibromatosis mimicking cystic retroperitoneal mass: case report and
      literature review.
AB  - BACKGROUND: Retroperitoneal desmoid-type fibromatosis (DF) is an uncommon
      mesenchymal neoplasm presenting as a firm mass with locally aggressive features.
      It usually manifests as a well-circumscribed or ill-defined, solid mass on cross
      sectional imaging. Cystic changes of DF have been described in the literature in
      association with prolonged medical treatment or abscess formation. However,
      spontaneous cystic change is rarely reported. CASE PRESENTATION: Here we report
      the case of a 46-year-old patient with a DF mimicked a large cystic tumor in the
      retroperitoneum. Ultrasonography and computed tomography were performed in order
      to search for localizations and characteristics of the cystic tumor. Radiological
      findings showed an oval cystic mass with a relatively thick wall, measuring 18.3
      * 12.3 * 21.5 cm in the left upper abdomen. Laparoscopic spleen-preserving distal
      pancreatectomy was performed and histopathological examination by
      immunohistochemical study enabled us to diagnose a DF invading the pancreatic
      parenchyma. The patient remained asymptomatic during an 8-month follow up period.
      CONCLUSIONS: We report an extremely rare case of retroperitoneal DF with
      spontaneous cystic change. DF can manifest as a mainly cystic mass with a thick
      wall, as in our case, which makes the correct diagnosis difficult. DF should be
      included in the preoperative differential diagnosis of a cystic retroperitoneal
      mass, regardless of its rarity.

PMID- 30223790
TI  - Comparative genotyping and phenotyping of Aspergillus fumigatus isolates from
      humans, dogs and the environment.
AB  - BACKGROUND: Aspergillus fumigatus is a ubiquitous saprotrophic fungus and an
      opportunistic pathogen of humans and animals. Humans and animals can inhale
      hundreds of A. fumigatus spores daily. Normally this is harmless for humans, but
      in case of immunodeficiency, invasive pulmonary aspergillosis (IPA) can develop
      with a high mortality rate. A. fumigatus also causes non-invasive mycoses like
      sino-nasal aspergillosis (SNA) in dogs. RESULTS: In this study we compared A.
      fumigatus isolates from humans with suspected IPA, dogs with SNA, and a set of
      environmental isolates. Phylogenetic inference based on calmodulin (CaM) and beta
      tubulin (benA) sequences did not reveal A. fumigatus sub-groups linked to the
      origin of the isolates. Genotyping and microsatellite analysis showed that each
      dog was infected by one A. fumigatus genotype, whereas human patients had mixed
      infections. Azole resistance was determined by antifungal susceptibility testing
      and sequencing of the cyp51A gene. A total of 12 out of 29 human isolates and 1
      out of 27 environmental isolates were azole resistant. Of the azole resistant
      strains, 11 human isolates showed TR34/L98H (n = 6) or TR46/Y121F/T289A (n = 5).
      Phenotypically, isolates from dogs were more variable in growth speed and
      morphology when compared to those isolated from human and the environment.
      CONCLUSIONS: 1. A. fumigatus from dogs with SNA are phenotypically very diverse
      in contrast to their environmental and human counterparts. 2. Phenotypic
      variability can be induced during the chronic infection process in the sinus of
      the dogs. The basis of this heterogeneity might be due to genomic differences
      and/or epigenetic variations. 3. Differences in dogs is a could be a result of
      within-host adaption and might be triggered by environmental factors in the
      sinus, however this hypothesis still needs to be tested.

PMID- 30223792
TI  - Effects of pretransplant peritoneal vs hemodialysis modality on outcome of first
      kidney transplantation from donors after cardiac death.
AB  - BACKGROUND: The effect of pretransplant peritoneal dialysis (PD) or hemodialysis
      (HD) modality on outcomes of kidney transplantation (KT) for end-stage renal
      disease (ESRD) is debatable. We evaluated the outcomes these modalities in KT
      from donor after cardiac death (DCD). METHODS: A cohort of 251 patients on HD, PD
      or pre-emptive who underwent first KT from DCD between January 2014 and December
      2016 were prospectively analyzed to compare for outcomes on recovery of renal
      function, complications as well as patient and graft survival. The patients were
      followed till August 2017. Data on 104 HD and 98 PD were available for final
      comparative outcome analysis, 5 pre-emptive were analyzed as the control group.
      RESULTS: Both HD and PD group patients were well matched for demographic and
      baseline characteristics. The follow-up period was 12.5 (3.0, 22.0) months in HD
      and 12.0 (6.0, 20.0) months in PD patients. Post-transplant renal functions
      between the two groups showed no differences. Among PD patients, 16 (16.3%)
      suffered delayed graft function, versus 19 (18.3%) in HD, with no statistical
      differences (p = 0.715). Complications of acute rejection, infections were
      comparable between the groups. The patient survival, graft survival and death
      censored graft survival were similar for HD and PD after adjusting for other
      multiple risk factors. CONCLUSIONS: Our results indicate that outcome of first KT
      from DCD is not affected by pretransplant dialysis modality of PD or HD in
      aspects of recovery of renal function, complications as well as patient and graft
      survival.

PMID- 30223794
TI  - MicroRNA profiling associated with muscle growth in modern broilers compared to
      an unselected chicken breed.
AB  - BACKGROUND: Genetically selected modern broiler chickens have acquired
      outstanding production efficiency through rapid growth and improved feed
      efficiency compared to unselected chicken breeds. Recently, we analyzed the
      transcriptome of breast muscle tissues obtained from modern pedigree male (PeM)
      broilers (rapid growth and higher efficiency) and foundational Barred Plymouth
      Rock (BPR) chickens (slow growth and poorer efficiency). This study was designed
      to investigate microRNAs that play role in rapid growth of the breast muscles in
      modern broiler chickens. RESULTS: In this study, differential abundance of
      microRNA (miRNA) was analyzed in breast muscle of PeM and BPR chickens and the
      results were integrated with differentially expressed (DE) mRNA in the same
      tissues. A total of 994 miRNA were identified in PeM and BPR chicken lines from
      the initial analysis of small RNA sequencing data. After filtering and
      statistical analyses, the results showed miR-2131-5p, miR-221-5p, miR-126-3p, miR
      146b-5p, miR-10a-5p, let-7b, miR-125b-5p, and miR-146c-5p up-regulated whereas
      miR-206 down-regulated in PeM compared to BPR breast muscle. Based on inhibitory
      regulations of miRNAs on the mRNA abundance, our computational analysis using
      miRDB, an online software, predicated that 118 down-regulated mRNAs may be
      targeted by the up-regulated miRNAs, while 35 up-regulated mRNAs appear to be due
      to a down-regulated miRNA (i.e., miR-206). Functional network analyses of target
      genes of DE miRNAs showed their involvement in calcium signaling, axonal guidance
      signaling, and NRF2-mediated oxidative stress response pathways suggesting their
      involvement in breast muscle growth in chickens. CONCLUSION: From the integrated
      analyses of differentially expressed miRNA-mRNA data, we were able to identify
      breast muscle specific miRNAs and their target genes whose concerted actions can
      contribute to rapid growth and higher feed efficiency in modern broiler chickens.
      This study provides foundation data for elucidating molecular mechanisms that
      govern muscle growth in chickens.

PMID- 30223793
TI  - Role of AMPK signalling pathway during compensatory growth in pigs.
AB  - BACKGROUND: The molecular basis of compensatory growth in monogastric animals has
      not yet been fully explored. Herewith, in this study we aim to determine changes
      in the pig skeletal muscle transcriptome profile during compensatory growth
      following a feed restriction period. A RNA-Seq experiment was performed with a
      total of 24 females belonging to a Duroc commercial line. Half of the animals
      received either a restricted (RE) or ad libitum (AL) diet during the first
      fattening period (60-125 d of age). After that, all gilts were fed ad libitum for
      a further ~30 d until the age of ~155 d, when animals were slaughtered and
      samples of gluteus medius muscle were harvested to perform RNA-Seq analyses and
      intramuscular fat content determination. RESULTS: During the period following
      food restriction, RE animals re-fed ad libitum displayed compensatory growth,
      showed better feed conversion rate and tended to deposit more subcutaneous fat
      than AL fed animals. Animals were slaughtered in the phase of accelerated growth,
      when RE animals had not completely compensated the performance of AL group,
      showing lower live and carcass weights. At intramuscular level, RE gilts showed a
      higher content of polyunsaturated fatty acids during the compensatory growth
      phase. The comparison of RE and AL expression profiles allowed the identification
      of 86 (|log2Fold-Change| > 1, padj < 0.05) differentially expressed (DE) genes. A
      functional categorization of these DE genes identified AMPK Signaling as the most
      significantly enriched canonical pathway. This kinase plays a key role in the
      maintenance of energy homeostasis as well as in the activation of autophagy.
      Among the DE genes identified as components of AMPK Signaling pathway, five out
      of six genes were downregulated in RE pigs. CONCLUSIONS: Animals re-fed after a
      restriction period exhibited a less oxidative metabolic profile and catabolic
      processes in muscle than animals fed ad libitum. The downregulation of autophagy
      observed in the skeletal muscle of pigs undergoing compensatory growth may
      constitute a mechanism to increase muscle mass thus ensuring an accelerated
      growth rate. These results reveal that the downregulation of AMPK Signaling plays
      an important role in compensatory growth in pigs.

PMID- 30223796
TI  - Adherence to driving cessation advice given to patients with cognitive impairment
      and consequences for mobility.
AB  - BACKGROUND: Driving is related to social participation; therefore older drivers
      may be reluctant to cease driving. Continuation of driving has also been reported
      in a large proportion of patients with cognitive impairment. The aim of this
      study is to investigate whether patients with cognitive impairment adhere to
      driving cessation advice after a fitness-to-drive assessment and what the
      consequences are with regard to mobility. METHODS: Patients with cognitive
      impairment (n = 172) participated in a fitness-to-drive assessment study,
      including an on-road driving assessment. Afterwards, patients were advised to
      either continue driving, to follow driving lessons, or to cease driving.
      Approximately seven months thereafter, patients were asked in a follow-up
      interview about their adherence to the driving recommendation. Factors
      influencing driving cessation were identified using a binary logistic regression
      analysis. Use of alternative transportation was also evaluated. RESULTS:
      Respectively 92 and 79% of the patients adhered to the recommendation to continue
      or cease driving. Female gender, a higher Clinical Dementia Rating-score,
      perceived health decline, and driving cessation advice facilitated driving
      cessation. Patients who ceased driving made use of less alternative modes of
      transportation than patients who still drove. Nonetheless, around 40% of the
      patients who ceased driving increased their frequency of cycling and/or public
      transport use. CONCLUSIONS: Adherence to the recommendations given after the
      fitness-to-drive assessments was high. Female patients were in general more
      likely to cease driving. However, a minority of patients did not adhere to
      driving cessation advice. These drivers with dementia should be made aware of the
      progression of their cognitive impairment and general health decline to
      facilitate driving cessation. There are large differences in mobility between
      patients with cognitive impairment. Physicians should discuss options for
      alternative transportation in order to promote sustained safe mobility of
      patients with cognitive impairment.

PMID- 30223795
TI  - Autozygosity islands and ROH patterns in Nellore lineages: evidence of selection
      for functionally important traits.
AB  - BACKGROUND: The aim of this study was to assess genome-wide autozygosity in a
      Nellore cattle population and to characterize ROH patterns and autozygosity
      islands that may have occurred due to selection within its lineages. It attempts
      also to compare estimates of inbreeding calculated from ROH (FROH), genomic
      relationship matrix (FGRM), and pedigree-based coefficient (FPED). RESULTS: The
      average number of ROH per animal was 55.15 +/- 13.01 with an average size of 3.24
      Mb. The Nellore genome is composed mostly by a high number of shorter segments
      accounting for 78% of all ROH, although the proportion of the genome covered by
      them was relatively small. The genome autozygosity proportion indicates moderate
      to high inbreeding levels for classical standards, with an average value of 7.15%
      (178.70 Mb). The average of FPED and FROH, and their correlations (- 0.05 to
      0.26) were low. Estimates of correlation between FGRM-FPED was zero, while the
      correlation (- 0.01 to - 0.07) between FGRM-FROH decreased as a function of ROH
      length, except for FROH > 8Mb (- 0.03). Overall, inbreeding coefficients were not
      high for the genotyped animals. Autozygosity islands were evident across the
      genome (n = 62) and their genomic location did not largely differ within
      lineages. Enriched terms (p < 0.01) associated with defense response to bacteria
      (GO:0042742), immune complex reaction (GO:0045647), pregnancy-associated
      glycoproteins genes (GO:0030163), and organism growth (GO:0040014) were described
      within the autozygotic islands. CONCLUSIONS: Low FPED-FROH correlation estimates
      indicate that FPED is not the most suitable method for capturing ancient
      inbreeding when the pedigree does not extend back many generations and FROH
      should be used instead. Enriched terms (p < 0.01) suggest a strong selection for
      immune response. Non-overlapping islands within the lineages greatly explain the
      mechanism underlying selection for functionally important traits in Nellore
      cattle.

PMID- 30223797
TI  - Standardized quality metric system for structural brain magnetic resonance images
      in multi-center neuroimaging study.
AB  - BACKGROUND: Multi-site neuroimaging offer several benefits and poses tough
      challenges in the drug development process. Although MRI protocol and clinical
      guidelines developed to address these challenges recommend the use of good
      quality images, reliable assessment of image quality is hampered by the several
      shortcomings of existing techniques. METHODS: Given a test image two feature
      images are extracted. They are grayscale and contrast feature images. Four binary
      images are generated by setting four different global thresholds on the feature
      images. Image quality is predicted by measuring the structural similarity between
      appropriate pairs of binary images. The lower and upper limits of the quality
      index are 0 and 1. Quality prediction is based on four quality attributes;
      luminance contrast, texture, texture contrast and lightness. RESULTS: Performance
      evaluation on test data from three multi-site clinical trials show good objective
      quality evaluation across MRI sequences, levels of distortion and quality
      attributes. Correlation with subjective evaluation by human observers is >= 0.6.
      CONCLUSION: The results are promising for the evaluation of MRI protocols,
      specifically the standardization of quality index, designed to overcome the
      challenges encountered in multi-site clinical trials.

PMID- 30223798
TI  - Prevalence and factors associated with abortion and unsafe abortion in Nepal: a
      nationwide cross-sectional study.
AB  - BACKGROUND: Abortion is one of the leading causes of maternal death in low- and
      middle-income countries. In Nepal, abortion is reported to be the third leading
      cause of maternal death. We aimed to investigate the prevalence and factors
      associated with abortion and unsafe abortion in Nepal. METHODS: This study is
      based on a nationally representative sample of the Nepal Demographic and Health
      Survey 2011. Women who had ever had a terminated pregnancy (n = 2395) were
      studied. The survey elicited information on the most recent abortion. Unsafe
      abortion was defined according to the providers of abortion services. Binary
      logistic regression was used to calculate odds ratios (ORs) and 95% Confidence
      Intervals (CIs) of abortions and unsafe abortions due to demographic, socio
      economic and lifestyle-related characteristics. The interaction of the reason for
      abortion with age and educational status in predicting unsafe abortion was
      calculated using the predictive margins and their 95% CI. RESULTS: The five-year
      prevalence of abortion was 21.1% among women of reproductive age who ever had a
      terminated pregnancy and 16.0% of total abortions were unsafe. Women of Buddhist
      religion (OR 2.15; 95% CI 1.04, 4.44), those who were literate (secondary level
      education OR 1.69; 95% CI 1.22, 2.34), those who knew about legal abortion (OR
      1.88; 95% CI 1.41, 2.52) and those who were aware of safe places for abortion
      services (OR 4.96; 95% CI 3.04, 8.09) were more likely to undergo an abortion.
      Likewise, women in age group 25-34 years (OR 0.43; 95% CI 0.19, 0.97) and those
      who were in the richest wealth quintile (OR 0.10; 95% CI 0.04, 0.25) were less
      likely to undergo an unsafe abortion. Educated women of 25-34 years reporting
      "health risk" as the reason for abortion had a decidedly lower probability (<
      10.0%) than the others of going through the unsafe abortion. CONCLUSIONS: The
      prevalence of abortion in Nepal remains high. Education, religion, age, knowledge
      about legal abortion and safe places to undergo abortion were the major decisive
      factors associated with abortion. Young, poorest and uneducated women were more
      likely to undergo unsafe abortions. Therefore, intervention studies among these
      target groups are warranted.

PMID- 30223799
TI  - A content analysis of popular media reporting regarding increases in minimum ages
      of legal access for tobacco.
AB  - BACKGROUND: In the late 20th century, US localities began increasing the minimum
      age of legal access (MLA) for tobacco from 18 to 21 years by enacting "Tobacco
      21" ordinances. Although these policies have a strong evidence base and broad
      popular support, popular media coverage of tobacco control laws has not always
      been accurate. This study sought to determine if contemporaneous popular media
      reporting accurately reflected the scientific findings regarding increased
      tobacco MLAs. METHODS: We searched LexisNexis for popular media reports that (1)
      addressed proposed or enacted Tobacco 21 ordinances and were (2) published in
      English, (3) drawn from a US news source, and (4) written after January 2004. We
      conducted a content analysis for quality based on a validated measure of accuracy
      of reporting, the Index of Scientific Quality (ISQ), which allows assessment of
      articles by assigning scores ranging from 1 (lowest) to 5 (highest). RESULTS:
      Searches yielded 378 articles; after screening for relevance and duplicates, 98
      were included in the review. All studies identified through the keyword searches
      addressed Tobacco 21 policies. The average global score identifying the
      scientific quality of the articles was 2.98 of 5. Over three-quarters of the
      popular media articles addressing Tobacco 21 laws were written after a systematic
      review of these policies was released by the Institute of Medicine and
      approximately 4 in 10 cited findings from that review. CONCLUSIONS: Popular media
      reports on Tobacco 21 laws demonstrated average overall quality and relied on
      both anecdotal and scientific evidence, in contrast to previous studies found
      that popular media reports on tobacco issues demonstrated low overall quality and
      relied primarily on anecdotal evidence. The systematic review of increased MLAs
      for tobacco written by the Institute of Medicine diffused quickly into popular
      reporting, suggesting that this type of evidence might improve research
      translation.

PMID- 30223801
TI  - Correction to: Managing the link and strengthening transition from child to adult
      mental health Care in Europe (MILESTONE): background, rationale and methodology.
AB  - Following publication of the original article [1], the authors reported they
      wanted to reinstate a co-author, who previously declined his authorship due to a
      misinterpretation of authorship limitations per research center.

PMID- 30223800
TI  - Development and validation of a new predictive model for breast cancer survival
      in New Zealand and comparison to the Nottingham prognostic index.
AB  - BACKGROUND: The only available predictive models for the outcome of breast cancer
      patients in New Zealand (NZ) are based on data in other countries. We aimed to
      develop and validate a predictive model using NZ data for this population, and
      compare its performance to a widely used overseas model, the Nottingham
      Prognostic Index (NPI). METHODS: We developed a model to predict 10-year breast
      cancer-specific survival, using data collected prospectively in the largest
      population-based regional breast cancer registry in NZ (Auckland, 9182 patients),
      and assessed its performance in this data set (internal validation) and in an
      independent NZ population-based series of 2625 patients in Waikato (external
      validation). The data included all women with primary invasive breast cancer
      diagnosed from 1 June 2000 to 30 June 2014, with follow up to death or Dec 31,
      2014. We used multivariate Cox proportional hazards regression to assess
      predictors and to calculate predicted 10-year breast cancer mortality, and
      therefore survival, probability for each patient. We assessed observed survival
      by the Kaplan Meier method. We assessed discrimination by the C statistic, and
      calibration by comparing predicted and observed survival rates for patients in 10
      groups ordered by predicted 10-year survival. We compared this NZ model with the
      Nottingham Prognostic Index (NPI) in this validation data set. RESULTS:
      Discrimination was good: C statistics were 0.84 for internal validity and 0.83
      for an independent external validity. For calibration, for both internal and
      external validity the predicted 10-year survival probabilities in all groups of
      patients, ordered by predicted survival, were within the 95% confidence intervals
      (CI) of the observed Kaplan-Meier survival probabilities. The NZ model showed
      good discrimination even within the prognostic groups defined by the NPI.
      CONCLUSIONS: These results for the New Zealand model show good internal and
      external validity, transportability, and potential clinical value of the model,
      and its clear superiority over the NPI. Further research is needed to assess
      other potential predictors, to assess the model's performance in specific
      subgroups of patients, and to compare it to other models, which have been
      developed in other countries and have not yet been tested in NZ.

PMID- 30223803
TI  - Comparing the needs and utilization of health services between urban residents
      and rural-to-urban migrants in China from 2012 to 2016.
AB  - BACKGROUND: With a large population of internal migrants from all over the world,
      China has the largest number of internal floating migrants, and most of them (up
      to 169 million in 2016) are rural-to-urban migrants. Those migrants have
      difficulty accessing essential health care services because of Hukou, leading to
      disparities in health needs and utilization between rural-to-urban migrants and
      residents. To compare the needs and utilization of health services between urban
      residents and rural-to-urban migrants in China from 2012 to 2016. METHOD: We used
      longitudinal data from the Chinese Labor Dynamic Survey (CLDS) with three waves
      in 2012, 2014 and 2016. Descriptive analysis was employed to show self-reported
      illnesses and health services utilization among locals and migrants in the most
      recent 2 weeks in China. Chi-square tests and log binomial regression models were
      constructed to explore factors influencing health care needs and utilization.
      RESULT: A total of 19.97% of respondents were rural-to-urban migrants, with an
      upward trend from 2012 to 2016. Rural-to-urban migrants (11.99%) had higher needs
      for health services than urban residents (10.47%) in general, while urban
      residents and migrants had no differences in needs in 2012. Besides, there was no
      difference in the utilization of health services between residents and migrants
      in 2012, 2014 or 2016. In addition, increased age, male sex, poor medical
      insurance coverage and dissatisfaction with income were found to have negative
      effects on health care needs. CONCLUSION: This study has shown that the rural-to
      urban migrants had higher health care needs but the same health care utilization
      compared with urban residents in China. Health policies focusing on equitable
      health outcomes should pay more attention to rural-to-urban migrants in China's
      health care system reform.

PMID- 30223802
TI  - EXclusion of non-Involved uterus from the Target Volume (EXIT-trial): an
      individualized treatment for locally advanced cervical cancer using modern
      radiotherapy and imaging techniques.
AB  - BACKGROUND: Definitive chemoradiotherapy is standard of care in locally advanced
      cervical cancer (LACC). Both toxicity and local relapse remain major concerns in
      this treatment. We hypothesize that a magnetic resonance imaging (MRI) based
      redefining of the radiotherapeutic target volume will lead to a reduction of
      acute and late toxicity. In our center, chemoradiotherapy followed by
      hysterectomy was implemented successfully in the past. This enables us to assess
      the safety of reducing the target volume but also to explore the biological
      effects of chemoradiation on the resected hysterectomy specimen. METHODS: The
      EXIT-trial is a phase II, single arm study aimed at LACC patients. This study
      evaluates whether a MRI-based exclusion of the non-tumor-bearing parts of the
      uterus out of the target volume results in absence of tumor in the non-high doses
      irradiated part of the uterus in the hysterectomy specimen. Secondary endpoints
      include a dosimetric comparison of dose on normal tissue when comparing study
      treatment plans compared to treatment of the whole uterus at high doses; acute
      and chronic toxicity, overall survival, local relapse- and progression-free
      survival. In the translational part of the study, we will evaluate the hypothesis
      that the baseline apparent diffusion coefficient (ADC) values of diffusion
      weighted MRI and its evolution 2 weeks after start of CRT, for the whole tumor as
      well as for intra-tumoral regions, is prognostic for residual tumor on the
      hysterectomy specimen. DISCUSSION: Although MRI is already used to guide target
      delineation in brachytherapy, the EXIT-trial is the first to use this information
      to guide target delineation in external beam radiotherapy. Early therapy
      resistance prediction using DW-MRI opens a window for early treatment adaptation
      or further dose-escalation on tumors/intratumoral regions at risk for treatment
      failure. TRIAL REGISTRATION: Belgian Registration: B670201526181 (prospectively
      registered, 26/11/2015); ClinicalTrials.gov Identifier: NCT03542942
      (retrospectively registered, 17/5/2018).

PMID- 30223804
TI  - Patient preferences concerning the efficacy and side-effect profile of
      schizophrenia medications: a survey of patients living with schizophrenia.
AB  - BACKGROUND: Despite the availability of numerous antipsychotic medications, many
      patients with schizophrenia continue to experience side effects that contribute
      to the overall burden of the illness. The present survey of patients with
      schizophrenia and schizoaffective disorder aimed to assess patient attitudes
      toward antipsychotic treatment, and understand key factors about willingness to
      try a new medication. METHODS: A cross-sectional survey was administered to 250
      patients with a primary clinical diagnosis of a schizophrenia spectrum disorder
      across five outpatient clinics in the United States. The survey included self
      reported gender, age, weight, and height, and questions about the importance of
      efficacy and side effects on the decision to take a prescribed antipsychotic
      medication. RESULTS: Patients rated efficacy and side effects as important
      attributes of antipsychotic treatment, with 93.6% and 83.6% of patients listing
      these as "very" or the "most" important factors in taking prescribed medication.
      A total of 87.6% of respondents identified the ability to think more clearly as
      an important property of their medication. Patients identified weight gain,
      physical restlessness, and somnolence as important side effects of current
      treatments ("very" or "most" important by 61.6%, 60.8%, and 58.8%, respectively).
      When asked about willingness to change antipsychotic medication, anticipated
      weight gain had a negative influence on willingness to try the new treatment,
      with 22.0% declining to try a medication that would lead to weight gain of 2.7
      4.5 kg (6-10 lb), 34.0% declining for anticipated weight gain of 5.0-9.1 kg (11
      20 lb), and 52.4% declining for anticipated weight gain greater than 9 kg (20
      lbs). CONCLUSION: Patients living with schizophrenia spectrum disorders are
      influenced by many factors when considering whether to take their medication,
      including efficacy and side effects. It is important for clinicians to assess
      specific patient concerns to develop a comprehensive treatment plan that
      maximizes adherence to the prescribed therapy.

PMID- 30223805
TI  - Constructions of alcohol consumption by non-problematised middle-aged drinkers: a
      qualitative systematic review.
AB  - BACKGROUND: Current research into alcohol consumption focuses predominantly on
      problematic drinkers and populations considered likely to engage in risky
      behaviours. Middle-aged drinkers are an under-researched group, despite emerging
      evidence that their regular drinking patterns may carry some risk. METHODS: We
      searched Scopus, Ovid Medline, and Ovid PsycInfo for peer-reviewed, English
      language publications appearing prior to 31 December 2015 and relating to the
      construction of alcohol consumption by middle-aged non-problematised drinkers.
      Thirteen papers were included in our thematic analysis. RESULTS: Middle-aged non
      problematised drinkers constructed their drinking practices by creating a
      narrative of normative drinking via discourses of gender, identity, play, and
      learning to drink. They also used drinking norms to construct their gender and
      identity. Health was not identified as a significant consideration for the
      population of interest when constructing alcohol consumption, except where
      drinking behaviours were likely to harm another. CONCLUSIONS: These results
      suggest that public health campaigns aimed at reducing alcohol consumption may be
      more effective if they focus on unacceptable drinking behaviours instead of
      personal health outcomes.

PMID- 30223806
TI  - Antioxidant and skin-whitening effects of aerial part of Euphorbia supina Raf.
      Extract.
AB  - BACKGROUND: Euphorbia supina (ES) has been widely used in folk medicine owing to
      its antibacterial, hemostatic, and anti-inflammatory properties. The aim of this
      study was to evaluate the antioxidant and skin-whitening effects of a 70% ethanol
      extract of ES. METHODS: The aerial parts of ES plant were extracted with 70%
      ethanol. The viability of B16F10 cells was evaluated by MTT assay to determine
      the non-toxic doses for further experiments. The tyrosinase and cellular
      tyrosinase activities were then measured using an enzyme-substrate assay. In
      addition, the expression of whitening-related proteins was measured using western
      blot. RESULTS: The antioxidant activity of the ES samples increased in a dose
      dependent manner, as confirmed by their radical scavenging activities in the 2,2
      diphenyl-1-1-picrylhydrazyl and 2,2-azino-bis-(3-ethylbenzthiazoline-6-sulfonic
      acid) assays. The ES extract significantly reduced tyrosinase activity and
      melanin content in a dose-dependent manner. Furthermore, it decreased alpha
      melanocyte stimulating hormone (MSH)-induced protein expression of tyrosinase and
      microphthalmia-associated transcription factor (MITF). CONCLUSIONS: Our results
      indicate that the ES extract attenuated alpha-MSH-stimulated melanin synthesis by
      modulating tyrosinase and MITF expression. Therefore, the ES extract could be a
      promising therapeutic agent to treat hyperpigmentation and as an ingredient for
      skin-whitening cosmetics.

PMID- 30223807
TI  - Yiqihuoxue decoction protects against post-myocardial infarction injury via
      activation of cardiomyocytes PGC-1alpha expression.
AB  - BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of
      ischemic heart disease, exacerbating cardiomyocytes injury in myocardial
      infarction (MI). Peroxisome proliferator-activated receptor gamma co-activator
      (PGC-1alpha) has been recognized as the key regulator of mitochondrial biogenesis
      and energy metabolism. Yiqihuoxue decoction (YQHX), a Traditional Chinese
      Medicine (TCM) prescription, can prevent and treat ischemic heart disease.
      However, the mechanisms of YQHX on PGC-1alpha expression in the ischemic heart
      have remained unclear. METHODS: Myocardial ischemia rat model and
      ischemia/hypoxia injury model in the cardiomyocytes were used to minic human
      cardiovascular disease. Rats were randomly assigned into 4 groups: Sham, Model,
      YQHX (8.2 g/kg) and Trimetazidine (10 mg/kg) group. 28 days after MI, cardiac
      functions and morphology were detected by echocardiography and HE staining,
      respectively. In vitro, the effects of YQHX on H9c2 cell viability, LDH and ROS
      were detected, respectively. PGC-1alpha relevant proteins were evaluated by
      Western blotting. RESULTS: In vivo, echocardiography and HE staining results
      showed that YQHX improved cardiac functions and modified pathological changes.
      YQHX enhanced PGC-1alpha expression and improved the mitochondrial ultrastructure
      and functions in rats MI model for 4 weeks. Further, we explored its potential
      mechanisms in cardiomyocytes. In vitro, YQHX significantly enhanced cell
      viability and reduced LDH release and ROS production induced by hypoxia in
      cardiomyocytes. Interestingly, exposure of cardiomyocytes to hypoxic conditions
      for 12 h induced the downregulation of PGC-1alpha expression, but the expression
      levels nearly returned to the normal state after hypoxia for 24 h. YQHX
      significantly enhanced PGC-1alpha expression between 12 h and 24 h induced by
      hypoxia through a mechanism associated with the activation of AMPK
      phosphorylation in H9c2 cells. In addition, YQHX upregulated the expression of
      Tfam and NRF-1, while NRF-1 expression was completely blocked by an AMPK
      inhibitor. YQHX largely restored the mitochondrial morphology and increased
      mitochondrial membrane potential in hypoxia-induced injury. Furthermore, the
      UHPLC-LTQ-Orbitrap-MSn analysis found that there were 87 chemical constituents in
      YQHX. CONCLUSIONS: These results suggest that the protective effect of YQHX on
      cardiomyocytes against hypoxia-induced injury may be attributed to activation of
      PGC-1alpha and maintenance of mitochondrial functions through a mechanism
      involving the activation of AMPK phosphorylation.

PMID- 30223808
TI  - A qualitative evaluation of hospital versus community-based management of
      patients on injectable treatments for tuberculosis.
AB  - BACKGROUND: Patients being treated for recurrent or multidrug-resistant
      tuberculosis (TB) require long courses of injectable anti-tuberculous agents. In
      order to maintain strong TB control programmes, it is vital that the experiences
      of people who receive long-term injectables for TB are well understood. To
      investigate the feasibility of a novel model of care delivery, a clinical trial
      (The TB-RROC Study) was conducted at two central hospitals in Malawi. Hospital
      based care was compared to a community-based approach for patients on TB
      retreatment in which 'guardians' (patient-nominated lay people) were trained to
      deliver injections to patients at home. This study is the qualitative evaluation
      of the TB-RROC trial. It examines the experiences of people receiving injectables
      as part of TB treatment delivered in hospital and community-based settings.
      METHODS: A qualitative evaluation of the TB-RROC intervention was conducted using
      phenomenographic methods. Trial participants were purposively sampled, and in
      depth interviews were conducted with patients and guardians in both arms of the
      trial. Key informant interviews and observations in the wards and community were
      performed. Thematic content analysis was used to derive analytical themes.
      RESULTS: Fourteen patients, 12 guardians and 9 key informants were interviewed.
      Three key themes relating to TB retreatment emerged: medical experiences
      (including symptoms, treatment, and HIV); the effects of the physical environment
      (conditions on the ward, disruption to daily routines and livelihoods); and trust
      (in other people, the community and in the health system). Experiences were
      affected by the nature of a person's prior role in their community and resulted
      in a range of emotional responses. Patients and guardians in the community
      benefited from better environment, social interactions and financial stability.
      Concerns were expressed about the potential for patients' health or relationships
      to be adversely affected in the community. These potential concerns were rarely
      realised. CONCLUSIONS: Guardian administered intramuscular injections were safe
      and well received. Community-based care offered many advantages over hospital
      based care for patients receiving long-term injectable treatment for TB and their
      families.

PMID- 30223809
TI  - Metronidazole-induced encephalopathy in a patient with pyogenic spondylitis: a
      case report.
AB  - BACKGROUND: Metronidazole is an antimicrobial agent commonly used in the
      treatment of several protozoal and anaerobic infections. Neurotoxicity associated
      with metronidazole has been rarely reported, and the incidence of metronidazole
      induced encephalopathy is unknown. Therefore, the accurate diagnosis of
      metronidazole-induced encephalopathy is often difficult because of the rarity of
      the disease. CASE PRESENTATION: An 86-year-old woman suffered from pyogenic
      spondylitis of the lumbar spine. Parvimonas micra, a gram-positive anaerobic
      bacterial species and a resident of the flora of the oral cavity, was identified
      in the biopsy specimens. Oral administration of metronidazole (1500 mg/day) was
      initiated. Forty-four days after initiating metronidazole (total intake of 66 g),
      she complained of tingling sensations in the upper limbs. After 4 days, she
      complained of additional symptoms including sensory disturbance of the tongue,
      dysarthria, and deglutition disorder. Characteristic brain magnetic resonance
      imaging findings on T2-weighted fluid-attenuated inversion recovery and diffusion
      weighted imaging led to the diagnosis of metronidazole-induced encephalopathy.
      Metronidazole was discontinued, and her neurological symptoms improved 10 days
      after discontinuation. At 14 days after discontinuation of oral metronidazole,
      abnormal findings on diffusion-weighted imaging almost disappeared. CONCLUSIONS:
      With the possibility of needing to prescribe metronidazole in the orthopedic
      field for the treatment of various infections, orthopedic surgeons are likely to
      encounter cases of metronidazole-induced encephalopathy. Thus, they should be
      able to recognize the condition and its potential complications. With increased
      awareness, early diagnosis with magnetic resonance imaging and discontinuation of
      metronidazole may become feasible when such patients are referred. Our report
      presents a detailed account of such a case, which may help in the early diagnosis
      and treatment of patients with metronidazole-induced encephalopathy. Furthermore,
      we recommend that patients treated with metronidazole should undergo careful and
      constant surveillance after starting antibiotic therapy.

PMID- 30223810
TI  - Schnyder corneal dystrophy and associated phenotypes caused by novel and
      recurrent mutations in the UBIAD1 gene.
AB  - BACKGROUND: The purpose of this study was to identify the genetic cause and
      describe the clinical phenotype of Schnyder corneal dystrophy (SCD) in six
      unrelated probands. METHODS: We identified two white Czech, two white British and
      two South Asian families with a clinical diagnosis of SCD. Ophthalmic assessment
      included spectral domain optical coherence tomography (SD-OCT) of one individual
      with advanced disease, and SD-OCT and confocal microscopy of a child with early
      stages of disease. UBIAD1 coding exons were amplified and Sanger sequenced in
      each proband. A fasting serum lipid profile was measured in three probands.
      Paternity testing was performed in one family. RESULTS: A novel heterozygous
      c.527G>A; p.(Gly176Glu) mutation in UBIAD1 was identified in one Czech proband.
      In the second Czech proband, aged 6 years when first examined, a previously
      described de novo heterozygous c.289G>A; p.(Ala97Thr) mutation was found. Two
      probands of South Asian descent carried a known c.305G>A; p.(Asn102Ser) mutation
      in the heterozygous state. Previously reported heterozygous c.361C>T;
      p.(Leu121Phe) and c.308C>T; p.(Thr103Ile) mutations were found in two white
      British families. Although crystalline deposits were present in all probands the
      affected area was small in some individuals. Corneal arcus and stromal haze were
      the most prominent phenotypical feature in two probands. In the Czech probands,
      SD-OCT confirmed accumulation of reflective material in the anterior stroma.
      Crystalline deposits were visualized by confocal microscopy. Mild dyslipidemia
      was found in all three individuals tested. CONCLUSION: Although de novo
      occurrence of mutations in UBIAD1 is extremely rare, SCD should be considered in
      the differential diagnosis of bilateral corneal haze and/or crystal deposition,
      especially in children.

PMID- 30223813
TI  - Chinese medical students' agreement with and fulfillment of the Physician
      Charter.
AB  - BACKGROUND: Although it has been nearly 15 years since the Medical
      Professionalism in the New Millennium: A Physician Charter (the Physician
      Charter) was proposed to reaffirm medical professionalism in response to the new
      challenges in healthcare delivery in the new century, the manner in which Chinese
      medical students agree with and fulfill the principles and responsibilities of
      professionalism defined in the Physician Charter still remains unknown. METHODS:
      In March 2016, 748 fifth-year medical students from China Medical University
      (CMU) participated in a survey in which they indicated their rate of agreement
      with and manner of fulfillment of the principles and responsibilities defined in
      the Physician Charter using a 10-point Likert scale. The data were then analyzed
      by t-tests, exploratory factor analysis, and multiple linear regressions.
      RESULTS: The total score of agreement with the Physician Charter was
      significantly higher than that of fulfillment (p < 0.001). The largest difference
      between agreement and fulfillment scores were with the principle of social
      justice (P3), commitments to improving access to care (R6), and a just
      distribution of finite resources (R7). Exploratory factor analysis distinguished
      two principles - primacy of patient welfare (P1) and patient autonomy (P2) - from
      the others in terms of the gap between agreement and fulfillment. This is
      partially because the proportion of students who rated agreement lower than
      fulfillment of P1 or P2 was much higher than it was for any other principle or
      responsibility. Additionally, multiple linear regressions show that students who
      are enrolled in a five-year program or who was registered as a rural resident
      (i.e. holding a rural Hukou) had significantly higher scores of agreement, but
      not fulfillment. CONCLUSIONS: Chinese medical students endorsed the Physician
      Charter and its core values of medical professionalism, although they felt
      difficult to fulfill in practice. Medical educators and the health authority
      should act together to support and foster professional values.

PMID- 30223812
TI  - A longitudinal observation study assessing changes in indicators of serious
      injury and violence with alcohol controls in four remote indigenous Australian
      communities in far north Queensland (2000-2015).
AB  - BACKGROUND: Legal restrictions on alcohol availability have been used to address
      violence and injury in the world's remote Indigenous communities. In Australia,
      alcohol management plans (AMPs) were implemented by the Queensland Government in
      2002. This study reports changes in indicators of alcohol-related violence and
      injury in selected communities. METHODS: Design and setting: A longitudinal
      observational study was conducted in four Aboriginal and Torres Strait Islander
      (Indigenous) communities in Cape York, far north Queensland. All communities are
      similarly-isolated from population centres where alcohol is available. DATA: For
      2000 to 2015 inclusive: 1019 Royal Flying Doctor Service aeromedical trauma
      retrievals; 5641 Queensland Police Service records of unique assault occurrences,
      including 2936 involving alcohol; and records for 2741 unique assault victims
      were examined. DATA ANALYSIS: Rates (per 1000 population) of trauma retrievals,
      assault occurrences and assault victims (per 1000 population) were compared
      across three policy phases. Phase 1: 2000 to 2008. Initial restrictions on
      possession and consumption of alcohol in 'restricted areas' were implemented
      during 2002-2003. Phase 2: 2009 to 2012. All alcohol was prohibited in three
      study communities and its legal availability limited in the fourth from 2009.
      Phase 3: 2013 to 2015. Government reviews of AMP policies in light of legal
      challenges and community responses characterise this phase. RESULTS: Compared
      with Phase 1, in Phase 2 retrieval rates declined by - 29.4%, assault occurrences
      by - 34.1% with less than one-third involving alcohol, and assault victims by -
      21.1%, reaching historically low levels in 2010-2012. These reductions did not
      continue consistently. Compared with Phase 1, in Phase 3 retrieval rates, assault
      occurrence rates and assault victim rates declined by somewhat lesser amounts, -
      13.9%, - 15.0% and - 13.4%, respectively. In Phase 3, the proportion of assault
      occurrences involving alcohol in communities 2, 3 and 4 rose towards pre-2008
      levels. CONCLUSIONS: Early successes of these controversial alcohol restrictions
      are jeopardised. Indicators of violence and injury appear to be rising once more
      in some AMP communities. Importantly, rates have not generally exceeded the
      highest levels seen in Phase 1. Fresh policy action is required with rigorous
      monitoring to prevent erosion of initial important successes.

PMID- 30223811
TI  - Identification of antitumoral agents against human pancreatic cancer cells from
      Asteraceae and Lamiaceae plant extracts.
AB  - BACKGROUND: Pancreatic cancer is one of the most aggressive and mortal cancers.
      Although several drugs have been proposed for its treatment, it remains resistant
      and new alternatives are needed. In this context, plants and their derivatives
      constitute a relevant source of bioactive components which might efficiently
      inhibit tumor cell progression. METHODS: In this study, we have analyzed the
      potential anti-carcinogenic effect of different Asteraceae (Achillea millefolium
      and Calendula officinalis) and Lamiaceae (Melissa officinalis and Origanum
      majorana) plant extracts obtained by different green technologies (Supercritical
      CO2 Extraction -SFE- and Ultrasonic Assisted Extraction -UAE-) to identify
      efficient plant extracts against human pancreatic cancer cells that could
      constitute the basis of novel treatment approaches. RESULTS: Asteraceae extracts
      showed better results as antitumoral agents than Lamiaceae by inducing
      cytotoxicity and inhibiting cell transformation, and SFE extracts were most
      efficient than UAE extracts. In addition, SFE derived plant extracts from
      Achillea millefolium and Calendula officinalis displayed synergism with the
      chemotherapeutic 5-Fluororacil. CONCLUSION: These results show how Yarrow and
      Marigold SFE-derived extracts can inhibit pancreatic cancer cell growth, and
      could be proposed for a comprehensive study to determine the molecular mechanisms
      involved in their bioactivity with the final aim to propose them as potential
      adjuvants in pancreatic cancer therapy.

PMID- 30223814
TI  - Calibration of confidence and assessed clinical skills competence in
      undergraduate paediatric OSCE scenarios: a mixed methods study.
AB  - BACKGROUND: The relationship between confidence and competence in clinical skills
      development is complex but important. This study aims to determine undergraduate
      paediatric student confidence in performing three common paediatric clinical
      skills framed as Objective Structured Clinical Examination (OSCE) scenarios and
      to compare this with subsequent assessed performance. The study also aims to
      explore possible barriers to successful paediatric skills completion. METHODS: A
      mixed-methods study was conducted on medical students. Cross-sectional
      questionnaire data relating to confidence in performing a number of paediatric
      skills were compared with assessed paediatric skills competency. Focus groups
      were carried out to identify themes in paediatric skills completion to
      triangulate this data. RESULTS: Eighty-five medical students participated in the
      study. Students had high levels of pre-test confidence in their ability to
      perform paediatrics skills. However agreement between pre-test confidence and
      subsequent task performance was poor and students had significantly greater
      belief in their skills ability than was subsequently demonstrated. Focus groups
      identified paediatric skills complexity, conflicting teaching and having limited
      supervised skills opportunities and as being possible contributory factors to
      this discrepancy. CONCLUSIONS: Student paediatric skills confidence is not
      matched by performance. The reasons for this are diverse but mostly modifiable. A
      major factor is the lack of supervised skills experience with appropriate
      feedback to support students in learning to calibrate their confidence against
      their competence. A number of recommendations are made including the introduction
      of formative assessment opportunities.

PMID- 30223815
TI  - Laparoscopic metabolic surgery for the treatment of type 2 diabetes in Asia: a
      scoping review and evidence-based analysis.
AB  - BACKGROUND: Laparoscopic metabolic surgery has been previously shown to be an
      effective treatment for obese patients with type 2 diabetes (T2DM). The objective
      of this scoping review is to determine the impact of metabolic surgery for the
      treatment of type 2 diabetes in Asia and perform an evidence-based analysis.
      METHODS: We performed a literature search in PubMed for research on laparoscopic
      metabolic surgery for the treatment of T2DM in Asia region. We classified the
      included studies based on the Oxford Center for Evidence Based Medicine
      guidelines. And performed and evidence analysis. RESULTS: In total, 205 articles
      were identified. 62.9% of the studies were from East Asia. The evidence of 26
      studies are level I, 59 are level II. Laparoscopic sleeve gastrectomy (LSG) was
      the most commonly reported surgical procedure (63.1%) in Asia. The number of
      laparoscopic metabolic surgery for T2DM in Asian countries has increased rapidly
      over the last 8 years. We identified 16 studies which showed that laparoscopic
      metabolic surgery is an effective and safe treatment for T2DM in patients with a
      BMI of > 25 kg/m2 to < 35 kg/m2 in Asia. CONCLUSIONS: Our results suggest that
      laparoscopic metabolic surgery might be an effective and safe treatment for T2DM
      patients with BMI < 35 kg/m2, and that LSG is the most commonly performed
      surgical procedure for this in Asia.

PMID- 30223816
TI  - Selection into medicine: the predictive validity of an outcome-based procedure.
AB  - BACKGROUND: Medical schools must select students from a large pool of well
      qualified applicants. A challenging issue set forward in the broader literature
      is that of which cognitive and (inter)personal qualities should be measured to
      predict diverse later performance. To address this gap, we designed a 'backward
      chaining' approach to selection, based on the competences of a 'good doctor'. Our
      aim was to examine if this outcome-based selection procedure was predictive of
      study success in a medical bachelor program. METHODS: We designed a multi-tool
      selection procedure, blueprinted to the CanMEDS competency framework. The
      relationship between performance at selection and later study success across a
      three-year bachelor program was examined in three cohorts. Study results were
      compared between selection-positive and selection-negative (i.e. primarily
      rejected) students. RESULTS: Selection-positive students outperformed their
      selection-negative counterparts throughout the entire bachelor program on
      assessments measuring cognitive (e.g. written exams), (inter)personal and
      combined outcomes (i.e. OSCEs). Of the 30 outcome variables, selection-positive
      students scored significantly higher in 11 cases. Fifteen other, non-significant
      between-group differences were also in favor of the selection-positives. An
      overall comparison using a sign test indicated a significant difference between
      both groups (p < 0.001), despite equal pre-university GPAs. CONCLUSIONS: The use
      of an outcome-based selection approach seems to address some of the predictive
      validity limitations of commonly-used selection tools. Selection-positive
      students significantly outperformed their selection-negative counterparts across
      a range of cognitive, (inter)personal, and mixed outcomes throughout the entire
      three-year bachelor in medicine.

PMID- 30223818
TI  - Personality functioning in anxiety disorders.
AB  - BACKGROUND: The Alternative DSM-5 Model for Personality Disorders as well as the
      upcoming IDC-11 have established a new focus on diagnosing personality disorders
      (PD): personality functioning. An impairment of self and interpersonal
      functioning in these models represents a general diagnostic criterion for a
      personality disorder. Little is known so far about the impairment of personality
      functioning in patients with other mental disorders than PD. This study aims to
      assess personality functioning in patients with anxiety disorders. METHODS:
      Ninety-seven patients with the diagnosis of generalized anxiety disorder, panic
      disorder, or phobia, and 16 healthy control persons were diagnosed using the
      Structured Clinical Interview for DSM-IV (SCID-I and -II) and were assessed by
      means of the Structured Interview for Personality Organization (STIPO) to
      determine the level of personality functioning. RESULTS: While all three patient
      groups showed significant impairment in personality functioning compared to the
      control group, no significant differences were observed between the different
      patient groups. In all three groups of anxiety disorders patients with comorbid
      PD showed significantly worse personality functioning than patients without.
      Patients without comorbid PD also yielded a significant impairment in their
      personality functioning when compared to the control group. CONCLUSIONS: Anxiety
      disorders are associated with a significant impairment in personality
      functioning, which is significantly increased by comorbid PD. There are no
      differences in terms of personality functioning between patients with different
      anxiety disorders.

PMID- 30223817
TI  - MiR-126 in intestinal-type sinonasal adenocarcinomas: exosomal transfer of MiR
      126 promotes anti-tumour responses.
AB  - BACKGROUND: Intestinal-type sinonasal adenocarcinomas (ITACs) are aggressive
      malignancies related to wood dust and leather exposure. ITACs are generally
      associated with advanced stage at presentation due to the insidious growth
      pattern and non-specific symptoms. Therefore, biomarkers that can detect the
      switch from the benign disease to malignancy are needed. Essential for tumour
      growth, angiogenesis is an important step in tumour development and progression.
      This process is strictly regulated, and MiR-126 considered its master modulator.
      METHODS: We have investigated MiR-126 levels in ITACs and compared them to benign
      sinonasal lesions, such as sinonasal-inverted papillomas (SIPs) and inflammatory
      polyps (NIPs). The tumour-suppressive functions of MiR-126 were also evaluated.
      RESULTS: We found that MiR-126 can significantly distinguish malignancy from
      benign nasal forms. The low levels of MiR-126 in ITACs point to its role in
      tumour progression. In this context, restoration of MiR-126 induced metabolic
      changes, and inhibited cell growth and the tumorigenic potential of MNSC cells.
      CONCLUSIONS: We report that MiR-126 delivered via exosomes from endothelial cells
      promotes anti-tumour responses. This paracrine transfer of MiRs may represent a
      new approach towards MiR-based therapy.

PMID- 30223819
TI  - Refining and testing the diagnostic accuracy of an assessment tool (PAT-POPS) to
      predict admission and discharge of children and young people who attend an
      emergency department: protocol for an observational study.
AB  - BACKGROUND: Increasing attendances by children (aged 0-16 years) to United
      Kingdom Emergency Departments (EDs) challenges patient safety within the National
      Health Service (NHS) with health professionals required to make complex
      judgements on whether children attending urgent and emergency care services can
      be sent home safely or require admission. Health regulation bodies have
      recommended that an early identification systems should be developed to recognise
      children developing critical illnesses. The Pennine Acute Hospitals NHS Trust
      Paediatric Observation Priority Score (PAT-POPS) was developed as an ED-specific
      tool for this purpose. This study aims to revise and improve the existing tool
      and determine its utility in determining safe admission and discharge decision
      making. METHODS/DESIGN: An observational study to improve diagnostic accuracy
      using data from children and young people attending the ED and Urgent Care Centre
      (UCC) at three hospitals over a 12 month period. The data being collected is part
      of routine practice; therefore opt-out methods of consent will be used. The
      reference standard is admission or discharge. A revised PAT-POPs scoring tool
      will be developed using clinically guided logistic regression models to explore
      which components best predict hospital admission and safe discharge. Suitable cut
      points for safe admission and discharge will be established using sensitivity and
      specificity as judged by an expert consensus meeting. The diagnostic accuracy of
      the revised tool will be assessed, and it will be compared to the former version
      of PAT-POPS using ROC analysis. DISCUSSION: This new predictive tool will aid
      discharge and admission decision-making in relation to children and young people
      in hospital urgent and emergency care facilities. TRIAL REGISTRATION: NIHR RfPB
      Grant: PB-PG-0815-20034. ClinicalTrials.gov: 213469. Retrospectively registered
      on 11 April 2018.

PMID- 30223820
TI  - Model-based roentgen stereophotogrammetric analysis using elementary geometrical
      shape models: 10 years results of an uncemented acetabular cup component.
AB  - BACKGROUND: Non-cemented acetabular cup components demonstrated different
      clinical performance depending on their surface texture or bearing couple.
      However, clinical osseointegration needs to be proved for each total joint
      arthroplasty (TJA) design. Aim of this study was to detect the in vivo migration
      pattern of a non-cemented cup design, using model-based roentgen
      stereophotogrammetric analysis with elementary geometrical shape models (EGS-RSA)
      to calculate early cup migration. METHODS: Interchangeable applicability of the
      model-based EGS-RSA method next to gold standard marker-based RSA method was
      assessed by clinical radiographs. Afterwards, in vivo acetabular cup migration
      for 39 patients in a maximum follow up of 120 months (10 years) was calculated
      using model-based EGS-RSA. RESULTS: For the axes with the best predictive
      capability for acetabular cup loosening, mean (+/-SD) values were calculated for
      migration and rotation of the cup. The cup migrated 0.16 (+/-0.22) mm along the
      cranio-caudal axis after 24 months and 0.36 (+/-0.72) mm after 120 months,
      respectively. It rotated - 0.61 (+/-0.57) deg. about the medio-lateral axis after
      24 months and - 0.53 (+/-0.67) deg. after 120 months, respectively. CONCLUSIONS:
      Interchangeable applicability of model-based EGS-RSA next to gold standard marker
      based RSA method could be shown. Model-based EGS-RSA enables an in vivo migration
      measurement without the necessity of TJA specific surface models. Migration of
      the investigated acetabular cup component indicates significant migration values
      along all the three axes. However, migration values after the second
      postoperative year were within the thresholds reported in literature, indicating
      no risk for later aseptic component loosening of this TJA design.

PMID- 30223821
TI  - Correlates of HIV status awareness among older adults in Uganda: results from a
      nationally representative survey.
AB  - BACKGROUND: Recent evidence suggests that HIV prevalence is generally higher
      among older than younger persons. However, few studies have explored issues
      regarding HIV testing and awareness of HIV status among older persons. We
      explored the correlates of HIV status awareness among older adults (aged 45+
      years) in Uganda. METHODS: This paper is based on secondary analysis of existing
      data on persons aged between 45 and 59 years from a nationally representative
      Uganda AIDS Indicator Survey which was conducted between February and September
      2011. Records on the socio-demographics and HIV/AIDS-specific indicators for 2472
      persons were extracted for analysis. Individuals were considered to be aware of
      their HIV status if they reported that they had tested and received their HIV
      test results within the past 12 months. Data analyses were done using the sample
      survey procedures to take into account the sampling structure of the data. Odds
      ratios were used to quantify the associations between receipt of HIV test results
      and potential factors. RESULTS: Of the 2472 respondents, 48% had ever tested and
      received their HIV test results while 23% tested and received their HIV results
      in the past 12 months or already knew that they are HIV positive. Individuals
      with the following characteristics had higher odds of being aware of their HIV
      status: being female (adjusted Odds Ratio (AOR) = 1.26; 95% CI: (1.04, 1.53),
      having high comprehensive knowledge of HIV/AIDS (AOR = 1.28; 95% CI: 1.04, 1.58),
      having attended secondary school education (AOR = 2.10; 95% CI: 1.47, 2.99) and
      engagement in high risk sexual behaviors (AOR = 1.53; 95% CI: (1.11, 2.10). A
      high level of stigma (holding at least three stigmatizing attitudes toward people
      living with HIV) was negatively correlated with awareness of HIV status (AOR
      =0.60; 95% CI: (0.45, 0.78). CONCLUSION: Less than a quarter of older Ugandans
      are aware of their current HIV status. High levels of stigma and low
      comprehensive knowledge of HIV/AIDS remained critical barriers to HIV testing and
      awareness of HIV status. These findings suggest a need for innovative HIV testing
      strategies to increase HIV status awareness among older adults in Uganda.

PMID- 30223822
TI  - An integrated approach to mental health and disaster preparedness: a cluster
      comparison with earthquake affected communities in Nepal.
AB  - BACKGROUND: On 25th April 2015, Nepal experienced a 7.8 magnitude earthquake,
      followed by countless aftershocks. Nearly 9000 people were killed and over
      600,000 homes destroyed. Given the high frequency of earthquake and other natural
      hazards in Nepal, disaster preparedness is crucial. However, evidence suggests
      that some people exposed to prior disasters do not engage in risk reduction, even
      when they receive training and have adequate resources. Mental health symptoms,
      including those associated with prior disaster exposure, may influence engagement
      in preparedness. Perceived preparedness for future disasters may in turn
      influence mental health. Social cohesion may influence both mental health and
      preparedness. METHODS: We developed and tested a hybrid mental health and
      disaster preparedness intervention in two earthquake-affected communities in
      Nepal (N = 240), about 2.5 months after the April 25th, 2015 earthquake. The 3
      day intervention was culturally adapted, facilitated by trained Nepalese
      clinicians and focused on enhancing disaster preparedness, mental health, and
      community cohesion. Communities were selected based on earthquake impacts and
      matched on demographic variables. The intervention was administered initially to
      one community, followed by the other receiving the intervention shortly
      thereafter. Survey data was collected across three time points. Focus groups were
      also conducted to examine intervention impact. RESULTS: At pre-intervention
      baseline, greater depression symptoms and lower social cohesion were associated
      with less disaster preparedness. Depression and PTSD were associated with lower
      social cohesion. Participation in the intervention increased disaster
      preparedness, decreased depression- and PTSD-related symptoms, and increased
      social cohesion. Mediation models indicated that the effect of intervention on
      depression was partially explained by preparedness. The effect of the
      intervention on disaster preparedness was partially explained by social cohesion,
      and the effect of intervention on depression and on PTSD was also partially
      explained by social cohesion. Data from focus groups illuminate participant
      perspectives on components of the intervention associated with preparedness,
      mental health and social cohesion. CONCLUSIONS: This mental health integrated
      disaster preparedness intervention is effective in enhancing resilience among
      earthquake-affected communities in Nepal. This brief, cost-effective group
      intervention has the potential to be scaled up for use with other communities
      vulnerable to earthquakes and other natural hazards. TRIAL REGISTRATION: Clinical
      Trials Registry-India, National Institute of Medical Statistics. Registration
      number: CTRI/2018/02/011688. http://ctri.nic.in/Clinicaltrials/login.php
      Retrospectively registered February 5th, 2018. First participant enrolled July
      2015.

PMID- 30223823
TI  - The Prejudice towards People with Mental Illness (PPMI) scale: structure and
      validity.
AB  - BACKGROUND: Although there is a substantial body of research on the stigma
      associated with mental illness, much of the extant research has not explicitly
      focused on the concept of prejudice, which drives discriminatory behaviour.
      Further, research that has investigated prejudice towards people with mental
      illness has conceptual, theoretical and psychometric limitations. To address
      these shortcomings, we sought to develop a new measure, the Prejudice towards
      People with Mental Illness (PPMI) scale, based on an improved conceptualisation
      and integration of the stigma and prejudice areas of research. METHODS: In
      developing the new scale, we undertook a thematic analysis of existing
      conceptualisations and measures to identify a pool of potential items for the
      scale which were subsequently assessed for fidelity and content validity by
      expert raters. We tested the structure, reliability, and validity of the scale
      across three studies (Study 1 N = 301; Study 2 N = 164; Study 3 N = 495) using
      exploratory factor, confirmatory factor, correlational, multiple regression, and
      ordinal logistic regression analyses using both select and general community
      samples. RESULTS: Study 1 identified four factors underlying prejudice towards
      people with mental illness: fear/avoidance, malevolence, authoritarianism, and
      unpredictability. It also confirmed the nomological network, that is, the links
      of these attitudes with the proposed theoretical antecedents and consequences.
      Studies 2 and 3 further supported the factor structure of the measure, and
      provided additional evidence for the nomological network. CONCLUSIONS: We argue
      that research into prejudice towards people with mental illness will benefit from
      the new measure and theoretical framework.

PMID- 30223825
TI  - Development and initial validation of an online engagement metric using virtual
      patients.
AB  - BACKGROUND: Considerable evidence in the learning sciences demonstrates the
      importance of engagement in online learning environments. The purpose of this
      work was to demonstrate feasibility and to develop and collect initial validity
      evidence for a computer-generated dynamic engagement score based on student
      interactions in an online learning environment, in this case virtual patients
      used for clinical education. METHODS: The study involved third-year medical
      students using virtual patient cases as a standard component of their educational
      program at more than 125 accredited US and Canadian medical schools. The
      engagement metric algorithm included four equally weighted components of student
      interactions with the virtual patient. We developed a self-report measure of
      motivational, emotional, and cognitive engagement and conducted confirmatory
      factor analysis to assess the validity of the survey responses. We gathered
      additional validity evidence through educator reviews, factor analysis of the
      metric, and correlations between student use of the engagement metric and self
      report measures of learner engagement. RESULTS: Confirmatory factor analysis
      substantiated the hypothesized four-factor structure of the survey scales.
      Educator reviews demonstrated a high level of agreement with content and scoring
      cut-points (mean Pearson correlation 0.98; mean intra-class correlation 0.98).
      Confirmatory factor analysis yielded an acceptable fit to a one-factor model of
      the engagement score components. Correlations of the engagement score with self
      report measures were statistically significant and in the predicted directions.
      CONCLUSIONS: We present initial validity evidence for a dynamic online engagement
      metric based on student interactions in a virtual patient case. We discuss
      potential uses of such an engagement metric including better understanding of
      student interactions with online learning, improving engagement through
      instructional design and interpretation of learning analytics output.

PMID- 30223826
TI  - Unilateral retinoblastoma with contralateral isolated choroidal Melanocytosis:
      case report of an unexpected presentation.
AB  - BACKGROUND: Congenital ocular melanocytosis has been shown to be extremely
      uncommon in studies of numerous infants and children with retinoblastoma and
      disorders such as retinopathy of prematurity. CASE PRESENTATION: A 33-month-old
      Caucasian boy presented with a solid white predominantly endophytic
      retinoblastoma filling most of the nasal aspect of the fundus and extensive
      vitreous seeding. Fundus exam of the contralateral eye showed a broad-based flat
      melanotic area of the choroid extending from the subfoveal region to the ora
      serrata temporally. The child was treated by enucleation of the retinoblastoma
      containing eye (homozygous non-germline RB1 mutation) and is being monitored
      annually. The patient has been followed for 4 years. CONCLUSIONS: This rare
      presentation of advanced unilateral retinoblastoma and contralateral isolated
      choroidal melanocytosis in a young child emphasizes the importance of detailed
      fundus mapping of the non-affected eye and has potential implications due to the
      increased incidence of uveal melanoma later in life.

PMID- 30223824
TI  - Microglia enhanced the angiogenesis, migration and proliferation of co-cultured
      RMECs.
AB  - BACKGROUND: Attention is increasingly being given to microglia-related
      inflammation in neovascular diseases, such as diabetic retinopathy and age
      related macular disease. Evidence shows that activated microglia contribute to
      disruption of the blood-retinal barrier, however, the mechanism is unclear. In
      this study, we aimed to clarify whether and how microglia affect the function of
      retinal microvascular endothelial cells (RMECs). METHODS: We activated microglia
      by Lipopolysaccharides (LPS) stimulation. After co-culturing static or activated
      microglia with RMECs using the Transwell system, we evaluated the function of
      RMECs. Vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth
      factor-BB (PDGF-BB) levels in the supernatant from the lower chamber were
      evaluated by ELISA. Angiogenesis, migration, and proliferation of RMECs were
      assessed by tube formation, wound healing, and WST-1 assays. The expression
      levels of tight junction proteins (ZO-1 and occludin) and endothelial markers
      (CD31 and CD34) were examined by Western blot analysis. RESULTS: We successfully
      established an LPS-activated microglia model and co-culture system of static or
      activated microglia with RMECs. In the co-culture system, we showed that
      microglia, especially activated microglia stimulated VEGF-A and PDGF-BB
      expression, enhanced angiogenesis, migration, proliferation, and permeability,
      and altered the phenotype of co-cultured RMECs. CONCLUSIONS: Microglia,
      especially activated microglia, play important roles in angiogenesis and
      maintenance of vascular function hemostasis in the retinal microvasculature. The
      mechanism needs further investigation and clarification.

PMID- 30223827
TI  - Ameliorative effect of taurine-chloramine in azathioprine-induced testicular
      damage; a deeper insight into the mechanism of protection.
AB  - BACKGROUND: The male reproductive system is a sensitive and intricate process
      that can be distressed following exposure to various toxicants. Therapeutic
      drugs, especially chemotherapeutics, can also adversely affect male fertility by
      instigating hormonal changes leading to testicular cells injury. Azathioprine
      (AZA) is an effective anticancer drug, but some cases of testicular toxicity have
      been reported. The aim of this work was to investigate the protective effects of
      taurine chloramine (TAU-Cl), a reported antioxidant and antiinflammtory peptide,
      against AZA-induced testicular dysfunction in male rats and ascertain the
      contributing mechanisms. METHODS: Forty male rats were allocated into four equal
      groups; (i) normal control rats, (ii) TAU-Cl group (100 mg/kg b.w/day for 10
      weeks, (iii) AZA group (5 mg/day for 4 weeks); (iv) TAU-Cl/AZA group. RESULTS:
      AZA caused increased DNA damage in the testes, and alterations in sex hormones
      and sperm quality, including sperm count, viability, and motility. Moreover,
      testicular tissue from the AZA-treated group had increased levels of oxidative
      stress indicator, MDA, and decreased activity of the antioxidant enzymes as
      superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) levels.
      These deleterious events were accompanied by upregulated levels of the pro
      inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), and protein
      expression of iNOS and NFkappaB-p65, interleukin-1beta (IL-1beta), and
      proapoptotic marker; caspase-9, together with decreased Bcl-2, NrF2 and
      hemeoxygenase (HO-1) expression. In contrast, TAU-Cl pretreatment significantly
      abrogated these toxic effects which were confirmed histologically. CONCLUSION:
      Pretreatment with TAU-Cl exerts a protective effect against AZA-induced male
      reproductive testicular atrophy. This finding could open new avenues for the use
      of TAU-Cl as a complementary approach to chemotherapy supportive care.

PMID- 30223828
TI  - Comprehensive assessment of left ventricular myocardial function by two
      dimensional speckle-tracking echocardiography.
AB  - BACKGROUND: Left ventricular ejection fraction (LVEF) results from the combined
      action of longitudinal and circumferential contraction, radial thickening, and
      basal and apical rotation. The study of these parameters together may lead to an
      accurate assessment of the cardiac function. METHODS: Ninety healthy volunteers,
      categorized by gender and age (<= 55 and >  55 years), were evaluated using two
      dimensional speckle tracking echocardiography. Transversal views of the left
      ventricle (LV) were obtained to calculate circumferential strain and left
      ventricular twist, while three apical views were obtained to determine
      longitudinal strain (LS) and mitral annular plane systolic excursion (MAPSE). We
      established the integral myocardial function of the LV according to: 1. The
      Combined Deformation Parameter (CDP), which includes Deformation Product (DP) -
      Twist x LS ( degrees  x %) - and Deformation Index (DefI) -Twist / LS ( degrees 
      / %)-; and 2. the Torsion Index (TorI): Twist / MAPSE ( degrees  / cm). RESULTS:
      The mean age of our patients was 50.3 +/- 11.1 years. CDP did not vary with
      gender or age. The average DP was - 432 +/- 172  degrees  x %, and the average
      DefI was - 0.96 +/- 0.36  degrees  / %. DP provides information about myocardial
      function (normal, pseudonormal, depressed), and the DefI quotient indicates which
      component (s) is/are affected in cases of abnormality. TorI was higher in
      volunteers over 55 years (16.5 +/- 15.2 vs 13.1 +/- 5.0  degrees /cm, p = 0.003),
      but did not vary with gender. CONCLUSIONS: The proposed parameters integrate
      values of twisting and longitudinal shortening. They allow a complete
      physiological assessment of cardiac systolic function, and could be used for the
      early detection and characterization of its alteration.

PMID- 30223830
TI  - Assessing practice pattern differences in the treatment of acute low back pain in
      the United States Military Health System.
AB  - BACKGROUND: Acute low back pain is one of the most common reasons for individuals
      to seek medical care in the United States. The US Military Health System provides
      medical care to approximately 9.4 million beneficiaries annually. These patients
      also routinely suffer from acute low back pain. Within this health system,
      patients can receive care and treatment from physicians, or physician extenders
      including physician assistants and nurse practitioners. Given the diversity of
      provider types and their respective training programs, it would be informative to
      evaluate variation in care delivery, adherence to clinical guidelines, and
      differences within the MHS among a complex mix of provider types. METHODS: This
      study was a retrospective, cross-sectional quantitative analysis that examined
      variations in treatment between provider types within the Military Health System
      in 2015 for treatment of acute low back pain using administrative data. In
      addition to descriptive and summary statistics, binomial logistic regression
      models were used to assess variation in practice patterns among physicians and
      mid-level practitioners for prescribing of non-steroidal anti-inflammatory,
      opioids, plain radiography, computed tomography, and magnetic resonance imaging.
      RESULTS: With regard to prescribing practices, results indicated that the odds of
      receiving non-steroidal anti-inflammatory prescriptions increased significantly
      for both physician assistants and nurse practitioners when compared to
      physicians. For basic radiological referrals, odds increased significantly for
      ordering plain radiography for physician assistants and nurse practitioners when
      compared to physicians. For more advanced imaging, odds significantly decreased
      for ordering computed tomography (CT) and slightly decreased for magnetic
      resonance for physician assistants, nurse practitioners and physician residents
      compared to the physician group. Additionally this study discovered differences
      in the prescribing patterns between provider categories. Both contractors and
      civilians had higher odds of prescribing opioids compared to active duty
      providers. CONCLUSIONS: As physician assistants and nurse practitioners continue
      to gain popularity as physician extenders in the US and in addressing provider
      shortages for the Military Health System, further research should be conducted to
      determine what impact, if any, the differences found in this study have on
      patient outcomes. In addition, provider type warrants further investigation to
      determine if labor mix and outsourcing decisions within a single payer system
      impacts health delivery and value based care.

PMID- 30223829
TI  - Adiposity mediates the association between whole grain consumption, glucose
      homeostasis and insulin resistance: findings from the US NHANES.
AB  - BACKGROUND: Growing evidence suggests an inverse association between whole grain
      (WG) consumption and insulin resistance (IR) or inflammation. However, it is
      still unclear whether adiposity plays a role in this relationship. We
      investigated whether the associations between WG intake with IR, glucose
      homeostasis and inflammation are mediated by adiposity in US adults. METHODS: The
      2005-2010 National Health and Nutrition Examination Surveys participants were
      included. WG intake was assessed and markers of IR and glucose homeostasis,
      inflammation, general and central adiposity. Analysis of co-variance and
      mediation analysis were applied, while accounting for survey design. RESULTS:
      Overall 16,621 participants were included in this analysis (mean age = 47.1
      years, 48.3% men). After adjustment for age, gender, and race, mean C-reactive
      protein (CRP), apolipoprotein B (apo-B), fasting blood glucose (FBG), insulin,
      homeostatic model assessment of IR (HOMA-IR) and beta cell function (HOMA-beta),
      hemoglobin A1c (HbA1c), and 2 h glucose after an oral glucose tolerance test
      decreased with increasing quarters of WG (all p < 0.001). Body mass index (BMI)
      had significant mediation effects on the associations between WG intake and CRP,
      apo-B, fasting glucose, insulin, HOMA-IR, HOMA-B, HbA1c, triglyceride to high
      density lipoprotein-cholesterol (TG:HDL-C) ratio and triglyceride-glucose (TyG)
      index (all p < 0.05) after adjustment for age, gender, race/ethnicity,
      educational status, smoking and level of physical activity. Both waist
      circumference (WC) and anthropometrically predicted visceral adipose tissue
      (apVAT) mediated the association between WG intakes with CRP, FBG, HbA1c, TG:HDL
      C ratio and TyG index, i.e. WC and apVAT had indirect effect (all p < 0.05).
      CONCLUSION: Our findings provide insights into the favourable impact of WG
      consumption on IR and inflammation, which may be affected by both central and
      visceral adiposity, i.e. the link between WG with IR and inflammation is more
      mediated in overweight/obese compared with lean individuals.

PMID- 30223831
TI  - "I will not stop visiting!" a qualitative study of community health workers'
      reluctance to withdraw household support following the end of a community-based
      intervention in Zimbabwe.
AB  - BACKGROUND: Community Health Worker (CHW) programmes are increasingly important
      in HIV service delivery. CHWs' familiarity with the local context can improve
      intervention acceptability and sustainability but concerns have been raised about
      potential exploitation and "burnout" of CHWs as they become emotionally involved
      in clients' lives. Little attention has been paid to what happens at the end of
      time-limited CHW interventions. This study aimed to examine the experience of
      CHWs' withdrawal from clients and their families. METHODS: We conducted a
      qualitative study of CHWs' experiences of "exiting" from households during the
      ZENITH (Zimbabwe Study for Enhancing Testing and Improving Treatment of HIV in
      Children) intervention, which provided 12 structured home visits over 72 weeks to
      families with children recently diagnosed with HIV. We conducted semi-structured
      interviews at 12 and 18 months with all 19 CHWs delivering the intervention and
      36 purposively selected caregivers who received home visits. Analysis focused on
      perceptions of the end of the trial, when CHWs completed the scheduled home-based
      visits and there was no guarantee of programme continuation beyond the study.
      RESULTS: Termination of scheduled home visits caused significant distress to both
      CHWs and the households they visited. We identify 3 thematic "lessons learned"
      for CHW programmes. First, CHWs derived pride and self-worth from emotional
      labour as they became integral to families' improved ability to cope, motivating
      them to go beyond formal job requirements. Second, clients' growing dependence on
      CHWs led to "exit" being interpreted as abandonment by both CHWs and households,
      causing distress on both sides. Finally, in response to anxiety about
      "abandoning" families, CHWs maintained contact with families long after scheduled
      withdrawal of services. CONCLUSIONS: CHWs can forge genuine bonds with
      households, creating expectations of long-term engagement. On the positive side,
      CHW derive pride from their work, attach social responsibility to their roles,
      and feel personal fulfilment in supporting families. If CHWs do not disengage
      from interventions as planned, or become demoralised by "exits", interventions
      will prove less sustainable. CHWs are often lauded for their ability to develop
      trust with peers, yet this willingness and ability to create enduring emotional
      bonds could threaten programme delivery.

PMID- 30223832
TI  - Correction to: HtrA1 expression and the prognosis of high-grade serous ovarian
      carcinoma: a cohort study using digital analysis.
AB  - It has been highlighted that the original article [1] contained a typesetting
      mistake in the family name of Dominique Trudel.

PMID- 30223833
TI  - HIV partner services in Kenya: a cost and budget impact analysis study.
AB  - BACKGROUND: The elicitation of contact information, notification and testing of
      sex partners of HIV infected patients (aPS), is an effective HIV testing strategy
      in low-income settings but may not necessarily be affordable. We applied WHO
      guidelines and the International Society for Pharmaco-economics and Outcomes
      Research (ISPOR) guidelines to conduct cost and budget impact analyses,
      respectively, of aPS compared to current practice of HIV testing services (HTS)
      in Kisumu County, Kenya. METHODS: Using study data and time motion studies, we
      constructed an Excel-based tool to estimate costs and the budget impact of aPS.
      Cost data were collected from selected facilities in Kisumu County. We report the
      annual total and unit costs of HTS, incremental total and unit costs for aPS, and
      the budget impact of scaling up aPS over a 5-year horizon. We also considered a
      task-shifted scenario that used community health workers (CHWs) rather than
      facility based health workers and conducted sensitivity analyses assuming
      different rates of scale up of aPS. RESULTS: The average unit costs for HIV
      testing among HIV-infected index clients was US$ 25.36 per client and US$ 17.86
      per client using nurses and CHWs, respectively. The average incremental costs for
      providing enhanced aPS in Kisumu County were US$ 1,092,161 and US$ 753,547 per
      year, using nurses and CHWs, respectively. The average incremental cost of
      scaling up aPS over a five period was 45% higher when using nurses compared to
      using CHWs (US$ 5,460,837 and US$ 3,767,738 respectively). Over the five years,
      the upper-bound budget impact of nurse-model was US$ 1,767,863, 63% and 35% of
      which were accounted for by aPS costs and ART costs, respectively. The CHW model
      incurred an upper-bound incremental cost of US$ 1,258,854, which was 71.2% lower
      than the nurse-based model. The budget impact was sensitive to the level of aPS
      coverage and ranged from US$ 28,547 for 30% coverage using CHWs in 2014 to US$
      1,267,603 for 80% coverage using nurses in 2018. CONCLUSION: Scaling aPS using
      nurses has minimal budget impact but not cost-saving over a five-year period.
      Targeting aPS to newly-diagnosed index cases and task-shifting to community
      health workers is recommended.

PMID- 30223835
TI  - Increased inflammation, endoplasmic reticulum stress and oxidative stress in
      endothelial and macrophage cells exacerbate atherosclerosis in ApoCIII transgenic
      mice.
AB  - BACKGROUND: Overexpression of apolipoprotein CIII (ApoCIII) leads to
      hypertriglyceridemia (HTG) which promotes atherosclerosis development. However,
      it remains unclear whether ApoCIII affects the atherosclerosis alone by promoting
      the inflammation and endoplasmic reticulum (ER) stress, or in combination with
      HTG. METHODS: Transgenic (ApoCIIItg) mouse models were used to investigate the
      atherogenic role of ApoCIII. Since endothelial cells and macrophages play crucial
      roles in atherosclerosis, we examined whether triglyceride-rich lipoproteins
      (TRLs), the major lipoproteins, in plasma of ApoCIIItg mice affect inflammation
      and ER stress levels in these cells. To further investigate the role of ApoCIII
      and triglyceride, we incubated HUVECs cells and peritoneal macrophages with TRLs
      with or without ApoCIII. RESULTS: Increased inflammation and ER stress were found
      in the aorta of ApoCIIItg mice. TRLs increased ER stress and oxidative stress in
      HUVECs and macrophages in a dose dependent. Moreover, TRLs together with ApoCIII
      could induce a higher inflammation level than TRLs alone in these cells.
      CONCLUSIONS: Both TRLs and ApoCIII contribute to the progression of
      atherosclerosis, and the modulation of TRLs and ApoCIII may represent a novel
      therapeutic approach against HTG induced atherosclerosis.

PMID- 30223834
TI  - What have we learned from observational studies and clinical trials of mild to
      moderate COPD?
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and
      mortality worldwide. It is well established that patients with mild to moderate
      disease represent the majority of patients with COPD, and patients with mild COPD
      already have measurable physiological impairment with increased morbidity and a
      higher risk of mortality compared with healthy non-smoking individuals. However,
      this subpopulation is both underdiagnosed and undertreated. In addition, most
      clinical trials include cohorts of patients with worse lung function and quality
      of life, which are very different from the milder patients usually seen in
      primary care.Clinical trials have shown that mild-moderate COPD patients present
      an improvement in lung function after treatment with long-acting bronchodilators
      (LABD). Inhaled therapy has also shown benefits in terms of symptoms, health
      related quality of life (HRQL) and exacerbation prevention in this population.
      Early intervention might have also a positive effect to prevent functional
      impairment. Nevertheless, there is scarce evidence from randomised clinical
      trials and real-life studies about the importance of pharmacological treatment in
      early stages of COPD to improve long-term outcomes. New concepts such as
      clinically important deterioration may help to investigate the impact of
      interventions on the natural history of the disease.

PMID- 30223836
TI  - Novel protein chip for the detection of antibodies against infectious bronchitis
      virus.
AB  - BACKGROUND: Infectious bronchitis (IB) caused by the IB virus (IBV) can cause
      acute damage to chickens around the world. Therefore, rapid diagnosis and immune
      status determination are critical for controlling IBV outbreaks. Enzyme-linked
      immunosorbent assays (ELISAs) have been widely used in the detection of IBV
      antibodies in the early infection and continuous infection of IB because they are
      more sensitive and quicker than other diagnostic methods. RESULTS: We have
      developed two indirect microarray methods to detect antibodies against IBV: a
      chemiluminescent immunoassay test (CIT) and a rapid diagnostic test (RDT). IBV
      nonstructural protein 5 (nsp5) was expressed, purified from Escherichia coli, and
      used to spot the initiator integrated poly(dimethylsiloxane), which can provide a
      near "zero" background for serological assays. Compared with the IDEXX IBV Ab
      Test kit, CIT and RDT have a sensitivity and specificity of at least 98.88% and
      91.67%, respectively. No cross-reaction was detected with antibodies against
      avian influenza virus subtypes (H5, H7, and H9), Newcastle disease virus, Marek's
      disease virus, infectious bursal disease virus, and chicken anemia virus. The
      coefficients of variation of the reproducibility of the intra- and inter-assays
      for CIT ranged from 0.8 to 18.63%. The reproducibility of RDT was consistent with
      the original results. The application of the IBV nsp5 protein microarray showed
      that the positive rate of the CIT was 96.77%, that of the nsp5 ELISA was 91.40%,
      and that of the RDT was 90.32%. Furthermore, the RDT, which was visible to the
      naked eye, could be completed within 15 min. Our results indicated that compared
      with nsp5 ELISA, the CIT was more sensitive, and the RDT had similar positive
      rates but was faster. Furthermore, the two proposed methods were specific and
      stable. CONCLUSIONS: Two microarray assays, which were rapid, specific,
      sensitive, and relatively simple, were developed for the detection of an antibody
      against IBV. These methods can be of great value for the surveillance of
      pathogens and monitoring the efficiency of vaccination.

PMID- 30223837
TI  - Comparison of non-triggered magnetic resonance imaging and echocardiography for
      the assessment of left atrial volume and morphology.
AB  - BACKGROUND: Advanced atrial fibrillation (AF) patients have persistent AF, failed
      previous catheter ablation and/or an enlarged left atrium (LA), which is
      associated with a reduced success of AF ablation. Transthoracic echocardiography
      (TTE) and contrast enhanced magnetic resonance angiography (CE-MRA) are available
      to assess LA volume. However, it is unknown how these modalities relate in
      patients with advanced AF. We therefore compared the reproducibility of TTE and
      non-triggered CE-MRA in advanced AF patients and their ability to select patients
      with successful thoracoscopic AF ablation. METHODS: Two independent observers
      measured LA volumes on 65 TTE and CE-MRA exams of advanced AF patients prior to
      AF ablation. Patients were followed after AF ablation with rhythm monitoring
      every 3 months for 1 year to determine AF recurrence. Inter-modality, inter- and
      intra-observer variability were determined using intraclass correlation
      coefficients (ICC). Receiver-operating characteristic (ROC) analysis was
      performed to determine sensitivity and specificity of TTE and CE-MRA volume and
      CE-MRA dimensions to identify patients with AF recurrence during follow-up.
      RESULTS: LA enlargement >= 34 ml/m2 was present in 60% of the patients. CE-MRA
      and TTE demonstrated a good correlation for LA volume assessment (intraclass
      correlation, ICC = 0.86; p < 0.001) with larger volumes consistently measured by
      CE-MRA. Major discrepancies were mostly attributed to TTE acquisition.
      Craniocaudal enlargement discriminated patients with AF recurrence (AUC 0.67 [95%
      CI 0.55-0.85], p = 0.01). CONCLUSIONS: Non-triggered CE-MRA is a viable and
      reproducible 3D alternative for 2D TTE to assess LA volume in advanced AF
      patients. Craniocaudal enlargement was the only discriminator of AF recurrence
      after AF ablation.

PMID- 30223838
TI  - Reliability of ultrasonography to detect inflammatory lesions and structural
      damage in juvenile idiopathic arthritis.
AB  - BACKGROUND: Musculoskeletal Ultrasonography (MSUS) is an important tool for the
      clinical assessment in Juvenile Idiopathic Arthritis (JIA). The objective of this
      study was to evaluate the reliability of MSUS to detect elementary lesions:
      synovitis, tenosynovitis, cartilage damage and bone erosions in the wrist and
      metacarpal (MCP) joints of patients with JIA. METHODS: Thirty children in various
      subgroups of JIA according to ILAR criteria, were included in this cross
      sectional study. Clinical data including painful, swollen and limited joints were
      recorded. Five rheumatologist ultrasonographers, blinded to the clinical
      evaluation, evaluated the presence of elementary lesions in the wrist and MCP 2
      and 3 joints bilaterally. The synovitis was graded in B-Mode and Power Doppler
      (PD). In addition to descriptive statistics intra- and inter-observer reliability
      was calculated using Cohen's kappa according to Landis and Koch. RESULTS: US
      detected more synovitis than the clinical examination (62% vs 28%, 30% vs 23% and
      22% vs 17% in the wrist, second and third MCP joints respectively). The intra
      observer concordance for synovitis in all joints was excellent in B-Mode (k 0.84
      .63-1.0 p = 0.001), except for MCP 2, where it was good (0.61, IC 95% .34-89, p =
      0.001). For both modalities (PD, B-Mode) tenosynovitis, cartilage damage and bone
      erosions it was also excellent. Regarding synovitis grading the concordance was
      excellent for all grades (0.83-1.0, IC 95% 0.51.1.0, p = 0.001), except for grade
      1 where it was good (0.61, IC 95% 0.43-.83, p = 0.001). Reliability inter
      observer for grayscale synovitis (0.67-0.95, IC 95% 0.67-1.0, p = 0.001),
      tenosynovitis grayscale (0.89, IC 95% 0.78-0.99, p.001), damage cartilage (0.89,
      IC 95% 0.78-0.99, p = 0.001), PD (0.66, IC 95% 0.39-1.0, p = 0.001). The
      concordance for grading synovitis was excellent, but for grayscale grade 1 and 2
      (.66, IC 95% .53-.74, p = 0.007) and PD grade 1 and 2 (0.63, IC 95% .58-.91, p =
      004) was good. CONCLUSIONS: The intra- and inter-observer reliability of MSUS for
      inflammatory and structural lesions is good to excellent for the wrist and MCP in
      patients with JIA.

PMID- 30223839
TI  - Assessing changing weather and the El Nino Southern Oscillation impacts on cattle
      rabies outbreaks and mortality in Costa Rica (1985-2016).
AB  - BACKGROUND: Rabies is a major zoonotic disease affecting humans, domestic and
      wildlife mammals. Cattle are the most important domestic animals impacted by
      rabies virus in the New World, leading to thousands of cattle deaths per year and
      eliciting large economic losses. In the New World, virus transmission in cattle
      is primarily associated with Desmodus rotundus, the common vampire bat. This
      study analyses the association of weather fluctuations and the El Nino Southern
      Oscillation (ENSO), with the occurrence and magnitude, in terms of associated
      mortality, of cattle rabies outbreaks. Data from the 100 cattle rabies outbreaks
      recorded between 1985 and 2016 in Costa Rica were analyzed. Periodograms for time
      series of rabies outbreaks and the El Nino 4 index were estimated. Seasonality
      was studied using a seasonal boxplot. The association between epidemiological and
      climatic time series was studied via cross wavelet coherence analysis.
      Retrospective space-time scan cluster analyses were also performed. Finally,
      seasonal autoregressive time series models were fitted to study linear
      associations between monthly number of outbreaks, monthly mortality rates and the
      El Nino 4 index, temperature, and rainfall. RESULTS: Large rabies mortality
      occurred towards the Atlantic basin of the country. Outbreak occurrence and size
      were not directly associated with ENSO, but were sensitive to weather variables
      impacted by ENSO. Both, ENSO phases and rabies outbreaks, showed a similar 5 year
      period in their oscillations. Cattle rabies mortality and outbreak occurrence
      increased with temperature, whereas outbreak occurrence decreased with rainfall.
      These results suggest that special weather conditions might favor the occurrence
      of cattle rabies outbreaks. CONCLUSIONS: Further efforts are necessary to
      articulate the mechanisms underpinning the association between weather changes
      and cattle rabies outbreaks. One hypothesis is that exacerbation of cattle rabies
      outbreaks might be mediated by impacts of weather conditions on common vampire
      bat movement and access to food resources on its natural habitats. Further eco
      epidemiological field studies could help to understand rabies virus transmission
      ecology, and to propose sound interventions to control this major veterinary
      public health problem.

PMID- 30223840
TI  - Dual-task training of children with neuromotor disorders during robot-assisted
      gait therapy: prerequisites of patients and influence on leg muscle activity.
AB  - BACKGROUND: Walking in daily life is complex entailing various prerequisites such
      as leg strength, trunk stability or cognitive and motor dual task (DT)
      activities. Conventional physiotherapy can be complemented with robot-assisted
      gait therapy (RAGT) and exergames to enhance the number of step repetitions,
      feedback, motivation, and additional simultaneously performed tasks besides
      walking (e.g., dual-task (DT) activities). Although DT gait training leads to
      improvements in daily ambulation in adult patient groups, no study has evaluated
      RAGT with a DT exergame in children with neurological gait disorders. Therefore,
      we investigated children's functional and cognitive prerequisites to walk
      physiologically during RAGT with a DT exergame and analysed the influence of DT
      on leg muscle activity. METHODS: Children and adolescents (6-18 years) with
      neurological gait disorders completed RAGT with and without a DT exergame in this
      quasi-experimental study. We assessed several measures on the body function and
      activity domains (according to the International Classification of Functioning,
      Disability, and Health (ICF)) and determined whether these measures could
      distinguish well between children who walked physiologically during the DT RAGT
      or not. We measured leg muscle activity with surface electrodes to identify
      changes in EMG-amplitudes and -patterns. RESULTS: Twenty-one children
      participated (7 females, 6.5-17.3 years, Gross Motor Function Classification
      System (GMFCS) levels I-IV). Most activity measures distinguished significantly
      between participants performing the DT exergame physiologically or not with
      moderate to good sensitivity (0.8 <= sensitivity<=1.0) and specificity (0.5 <=
      specificity<=0.9). Body function measures differentiated less well. Despite that
      the EMG-amplitudes of key stance muscles were significantly lower during DT
      versus no DT exergaming, the mean activation patterns of all muscles correlated
      high (rho > 0.75) between the conditions. CONCLUSION: This study is the first
      that investigated effects of a DT exergame during RAGT in children with
      neurological gait disorders. Several performance measures could differentiate
      well between patients who walked with physiological versus compensatory movements
      while performing the DT exergame. While the DT exergame affected the leg muscle
      activity amplitudes, it did not largely affect the activity patterns of the
      muscles.

PMID- 30223842
TI  - Validation of the Korean version of the avoidance endurance behavior
      questionnaire in patients with chronic pain.
AB  - BACKGROUND: The avoidance-endurance model suggests both fear-avoidance responses
      and endurance-related responses could affect the chronicity of pain. Proper pain
      intervention requires measuring fear-avoidance responses and endurance-related
      responses but no Korean language questionnaire has yet been made to measure them.
      The purpose of this study was to evaluate the validity and reliability of the
      Korean version of the Avoidance-Endurance Behavior Questionnaire (K-AEQ-Behavior)
      by adapting the behavioral responses of Avoidance-Endurance Questionnaire into
      Korean language. METHODS: The K-AEQ-Behavior was forward and backward translated
      based on the standards for instrument translation. A total of 136 outpatients
      with chronic pain of a duration exceeding 3 months were recruited from a pain
      center at a university hospital in Seoul, Korea. Two weeks later, the K-AEQ
      Behavior was re-administered to 36 patients for test-retest reliability.
      Exploratory factor analysis was performed using principle axis factoring. The
      internal consistency, test-retest reliability, and concurrent validity of the K
      AEQ-Behavior were measured by Cronbach's ?, intraclass correlation coefficient,
      and Pearson correlation coefficient, respectively. RESULTS: Although the four
      factor structure (23 items) was derived in the original study, the two-factor
      structure of avoidance behavior and endurance behavior (21 items) was derived in
      the exploratory factor analysis of the Korean version in this study. Other
      results indicated that K-AEQ-Behavior has good internal consistency, test-retest
      reliability and concurrent validity. CONCLUSION: This study suggests that the K
      AEQ-Behavior is a reliable and valid instrument for assessing avoidance behavior
      and endurance behavior in patients with chronic pain.

PMID- 30223841
TI  - The prevalence of submicroscopic Plasmodium falciparum gametocyte carriage and
      multiplicity of infection in children, pregnant women and adults in a low malaria
      transmission area in Southern Ghana.
AB  - BACKGROUND: The gametocyte stage of Plasmodium falciparum is considered an
      important target for disrupting malaria transmission. Indications are that
      various demographic groups, such as children and pregnant women may differ in
      risk of harbouring gametocytes, which may be crucial for targeted control. In
      this study, the relationship between the prevalence and multiplicity of P.
      falciparum, asexual parasite infections and gametocytaemia was assessed in three
      different demographic groups in an area of southern Ghana with low malaria
      endemicity. Levels of antibody responses to Pfs230 were also assessed as a proxy
      for the presence of gametocytes. METHODS: The study involved multiple cross
      sectional sampling of children (N = 184, aged 2-15 years), male and non-pregnant
      female adults (N = 154, aged 16-65 years) and pregnant women (N = 125, aged 18-45
      years) from Asutsuare in the Shai Osudoku District of Greater Accra Region in
      Ghana. Asexual parasitaemia was detected by microscopy and PCR, and
      gametocytaemia was assessed by Pfs25-real time PCR. Multiclonal P. falciparum
      infections were estimated by msp2 genotyping and an indirect ELISA was used to
      measure plasma IgG antibodies to Pfs230 antigen. RESULTS: Overall, children and
      pregnant women had higher prevalence of submicroscopic gametocytes (39.5% and
      29.7%, respectively) compared to adults (17.4%). Multiplicity of infection
      observed amongst children (3.1) and pregnant women (3.9) were found to be
      significantly higher (P = 0.006) compared with adults (2.7). Risk of gametocyte
      carriage was higher in individuals infected with P. falciparum having both Pfmsp2
      3D7 and FC27 parasite types (OR = 5.92, 95% CI 1.56-22.54, P = 0.009) compared
      with those infected with only 3D7 or FC27 parasite types. In agreement with the
      parasite prevalence data, anti-Pfs230 antibody levels were lower in gametocyte
      positive adults (beta = - 0.57, 95% CI - 0.81, - 0.34, P < 0.001) compared to
      children. CONCLUSIONS: These findings suggest that children and pregnant women
      are particularly important as P. falciparum submicroscopic gametocyte reservoirs
      and represent important focus groups for control interventions. The number of
      clones increased in individuals carrying gametocytes compared to those who did
      not carry gametocytes. The higher anti-gametocyte antibody levels in children
      suggests recent exposure and may be a marker of gametocyte carriage.

PMID- 30223843
TI  - Analysis of clinical malaria disease patterns and trends in Vietnam 2009-2015.
AB  - BACKGROUND: Viet Nam has made tremendous progress towards reducing mortality and
      morbidity associated with malaria in recent years. Despite the success in malaria
      control, there has been a recent increase in cases in some provinces. In order to
      understand the changing malaria dynamics in Viet Nam and measure progress towards
      elimination, the aim of this study was to describe and quantify spatial and
      temporal trends of malaria by species at district level across the country.
      METHODS: Malaria case reports at the Viet Nam National Institute of Malariology,
      Parasitology, and Entomology were reviewed for the period of January 2009 to
      December 2015. The population of each district was obtained from the Population
      and Housing Census-2009. A multivariate (insecticide-treated mosquito nets [ITN],
      indoor residual spraying [IRS], maximum temperature), zero-inflated, Poisson
      regression model was developed with spatial and spatiotemporal random effects
      modelled using a conditional autoregressive prior structure, and with posterior
      parameters estimated using Bayesian Markov chain Monte Carlo simulation with
      Gibbs sampling. Covariates included in the models were coverage of intervention
      (ITN and IRS) and maximum temperature. RESULTS: There was a total of 57,713
      Plasmodium falciparum and 32,386 Plasmodium vivax cases during the study period.
      The ratio of P. falciparum to P. vivax decreased from 4.3 (81.0% P. falciparum;
      11,121 cases) in 2009 to 0.8 (45.0% P. falciparum; 3325 cases) in 2015. Coverage
      of ITN was associated with decreased P. falciparum incidence, with a 1.1% (95%
      credible interval [CrI] 0.009%, 1.2%) decrease in incidence for 1% increase in
      the ITN coverage, but this was not the case for P. vivax, nor was it the case for
      IRS coverage. Maximum temperature was associated with increased incidence of both
      species, with a 4% (95% CrI 3.5%, 4.3%) and 1.6% (95% CrI 0.9%, 2.0%) increase in
      P. falciparum and P. vivax incidence for a temperature increase of 1  degrees C,
      respectively. Temporal trends of P. falciparum and P. vivax incidence were
      significantly higher than the national average in Central and Central-Southern
      districts. CONCLUSION: Interventions (ITN distribution) and environmental factors
      (increased temperature) were associated with incidence of P. falciparum and P.
      vivax during the study period. The factors reviewed were not exhaustive, however
      the data suggest distribution of resources can be targeted to areas and times of
      increased malaria transmission. Additionally, changing distribution of the two
      predominant malaria species in Viet Nam will require different programmatic
      approaches for control and elimination.

PMID- 30223844
TI  - The factors that influence oral health-related quality of life in young adults.
AB  - BACKGROUND: Young adulthood is a time when subjects transform their role from a
      dependent child to an independent social identity. This cross-sectional study
      aimed to analyze the sociodemographic and clinical factors that may influence the
      OHRQoL of 18-year-old young adults. METHODS: A representative sample was selected
      from Hong Kong. Periodontal status and caries were examined according to WHO
      criteria. Four orthodontic indices were used to assess malocclusion. The oral
      health impact profile (OHIP-14) was used to measure OHRQoL. Adjusted OR was
      calculated by ordinal logistic regression. RESULTS: A total of 300 eligible
      subjects (165 females, 135 males) were recruited. Females had more severe caries
      than males; however, gender was not a significant factor of OHRQoL. Household
      income affected OHRQoL more than parents' education did: household income had
      effects on physical pain, psychological discomfort, psychological disability, and
      the total OHIP; while parents' education had some effects on functional
      limitation, physical pain and psychological discomfort. As for clinical factors,
      unhealthy periodontal conditions were more prevalent than caries (94.67% vs.
      59.00%); however, both of them showed no effect on OHRQoL. Malocclusion had a
      negative effect on OHRQoL; the most affected subscales were psychological
      discomfort and psychological disability. CONCLUSION: In this study, family
      ecosocial factors and malocclusion had an effect on OHRQoL. Among the family
      ecosocial factors, it was household income that had the most effect on OHRQoL.
      Malocclusion mainly affected the subscales of psychological discomfort and
      psychological disability. Gender, periodontal status and caries had no effect on
      young adults' OHRQoL.

PMID- 30223845
TI  - Emergence of HIV-1 drug resistance mutations in mothers on treatment with a
      history of prophylaxis in Ghana.
AB  - BACKGROUND: Antiretrovirals have been available in Ghana since 2003 for HIV-1
      positive pregnant women for prevention of mother-to-child transmission (PMTCT).
      Suboptimal responses to treatment observed post-PMTCT interventions necessitated
      the need to investigate the profile of viral mutations generated. This study
      investigated HIV-1 drug resistance profiles in mothers in selected centres in
      Ghana on treatment with a history of prophylaxis. METHODS: Genotypic Drug
      Resistance Testing for HIV-1 was carried out. Subtyping was done by phylogenetic
      analysis and Stanford HIV Database programme was used for drug resistance
      analysis and interpretation. To compare the significance between the different
      groups and the emergence of drug resistance mutations, p values were used.
      RESULTS: Participants who had prophylaxis before treatment, those who had
      treatment without prophylaxis and those yet to initiate PMTCT showed 32% (8), 5%
      (3) and 15% (4) HIV-1 drug resistance associated mutations respectively. The
      differences were significant with p value < 0.05. Resistance Associated Mutations
      (RAMs) were seen in 14 participants (35%) to nucleoside reverse transcriptase
      inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs).
      The most common NRTI mutation found was M184 V; K103 N and A98G were the most
      common NNRTI mutations seen. Thymidine Analogue Mutations (TAMs) such as M41 L,
      K70R and T215Y were found in all the groups; the most common of the TAMs found
      were M41 L and T215Y. Majority of the subtypes were CRF02_AG (82%). CONCLUSION:
      In Ghana initiation of uninterrupted treatment upon diagnosis, coupled with drug
      resistance testing, would produce a better treatment outcome for HIV-1 positive
      pregnant women.

PMID- 30223846
TI  - Comparison of clinical outcomes between mesh-reinforced pancreatojejunostomy and
      pancreatogastrostomy following pancreaticoduodenectomy: a cohort study.
AB  - BACKGROUND: Postoperative complications, especially postoperative pancreatic
      fistulas, remain the major concern following pancreaticoduodenectomy (PD). Mesh
      reinforced pancreatic anastomoses, including pancreatojejunostomy (PJ) and
      pancreatogastrostomy (PG), are a new effective technique in PD. This study was
      conducted to analyze the safety and efficacy of this new technique and to compare
      the results of mesh-reinforced PJ vs PG. METHODS: A total of 110 patients who
      underwent PD between August 2005 and January 2016 were eligible in this study.
      Perioperative and postoperative data of patients with a mesh-reinforced technique
      were analyzed. Data were also grouped according to the procedure performed: mesh
      reinforced PJ and mesh-reinforced PG. RESULTS: Among patients undergoing PD with
      the mesh-reinforced technique, 42 had postoperative complications, and the
      comprehensive complication index (CCI) was 32.7 +/- 2.5. Only 10% of patients had
      pancreatic fistula; three were grade A, six were grade B, and two were grade C.
      Biliary fistula occurred in only 8.2% of patients. Patients undergoing mesh
      reinforced PG showed a significantly lower rate of CCI than did mesh-reinforced
      PJ patients (27.0 +/- 2.1 vs 37.0 +/- 3.9, p < 0.05). The mesh-reinforced PG was
      also favored over mesh-reinforced PJ because of significant differences in intra
      abdominal fluid collection (5.9% vs 18.6%, p < 0.05) and delayed gastric emptying
      (3.9% vs 15.3%, p < 0.05). CONCLUSIONS: PD with the mesh-reinforced technique was
      a safe and effective method of decreasing postoperative pancreatic fistula.
      Compared with mesh-reinforced PJ, mesh-reinforced PG did not show significant
      differences in the rates of pancreatic fistula or biliary fistula. However, CCI,
      intra-abdominal fluid collection, and delayed gastric emptying were significantly
      reduced in patients with mesh-reinforced PG.

PMID- 30223847
TI  - Relational coordination in interprofessional teams and its effect on patient
      reported benefit and continuity of care: a prospective cohort study from
      rehabilitation centres in Western Norway.
AB  - BACKGROUND: Rehabilitation services depend on competent professionals who
      collaborate effectively. Well-functioning interprofessional teams are expected to
      positively impact continuity of care. Key factors in continuity of care are
      communication and collaboration among health care professionals in a team and
      their patients. This study assessed the associations between team functioning and
      patient-reported benefits and continuity of care in somatic rehabilitation
      centres. METHODS: This prospective cohort study uses survey data from 984
      patients and from health care professionals in 15 teams in seven somatic
      rehabilitation centres in Western Norway. Linear mixed effect models were used to
      investigate associations between the interprofessional team communication and
      relationship scores (measured by the Relational Coordination [RC] Survey and
      patient-reported benefit and personal-, team- and cross-boundary continuity of
      care. Patient-reported continuity of care was measured using the Norwegian
      version of the Nijmegen Continuity Questionnaire. RESULTS: The mean communication
      score for healthcare teams was 3.9 (standard deviation [SD] = 0.63, 95%
      confidence interval [CI] = 3.78, 4.00), and the mean relationship score was 4.1
      (SD = 0.56, 95% CI = 3.97, 4.18). Communication scores in rehabilitation teams
      varied from 3.4-4.3 and relationship scores from 3.6-4.5. Patients treated by
      teams with higher relationship scores experienced better continuity between
      health care professionals in the team at the rehabilitation centre (b = 0.36, 95%
      CI = 0.05, 0.68; p = 0.024). There was a positive association between RC
      communication in the team the patient was treated by and patient-reported
      activities of daily living benefit score; all other associations between RC
      scores and rehabilitation benefit scores were not significant. CONCLUSION: Team
      function is associated with better patient-reported continuity of care and higher
      ADL-benefit scores among patients after rehabilitation. These findings indicate
      that interprofessional teams' RC scores may predict rehabilitation outcomes, but
      further studies are needed before RC scores can be used as a quality indicator in
      somatic rehabilitation.

PMID- 30223848
TI  - The diagnostic value of [18F]-FDG-PET/CT in assessment of radiation renal injury
      in Tibet minipigs model.
AB  - BACKGROUND: Radiation-induced kidney damage can severely affect renal function,
      and have a serious impact on glucose reabsorption. Fluoro-2-deoxyglucose positron
      emission tomography (FDG-PET) is routinely utilized for metabolic imaging of
      glucose utilization. In this study, we are trying to assess the diagnostic value
      of 18F-FDG-PET/CT on measuring hyperacute effect of total body irradiation (TBI)
      on the kidneys. METHODS: Forty-eight Tibet minipigs were treated by TBI of
      different dosages using an 8-MV X-ray linear accelerator. Whole-body 18F-FDG
      PET/CT was performed at 6, 24 and 72 h followed by histologic examination, blood
      samples' and renal function analysis. RESULTS: The uptake of 18F-FDG was
      significantly different between 11/14 Gy dose groups and control group, the
      standard Uptake Values reached a maximal level at 72 h after 14-Gy TBI treatment.
      At doses over 8 Gy, histological observation showed formation of tube casts,
      degeneration, necrosis of tubular cells, inflammatory cell infiltration and
      dilatation of the mitochondria of tubule cells. Renal function analysis confirmed
      the changes in blood urea nitrogen and creatinine levels at various dosages and
      time intervals. Immunohistochemistry and western blot results indicate that the
      expression levels of IL-10 and TNF-alpha proteins were positively correlated with
      radiation dose up to 8 Gy. CONCLUSIONS: 18F-FDG PET/CT can reflect pathological
      changes in kidneys and it may be a useful tool for rapid and non-invasive
      assessment in cases of suspected radiation-induced kidney damage.

PMID- 30223849
TI  - The role of diffusion tensor imaging as an objective tool for the assessment of
      motor function recovery after paraplegia in a naturally-occurring large animal
      model of spinal cord injury.
AB  - BACKGROUND: Traumatic spinal cord injury (SCI) results in sensory and motor
      function impairment and may cause a substantial social and economic burden. For
      the implementation of novel treatment strategies, parallel development of
      objective tools evaluating spinal cord (SC) integrity during motor function
      recovery (MFR) is needed. Diffusion tensor imaging (DTI) enables in vivo
      microstructural assessment of SCI. METHODS: In the current study, temporal
      evolvement of DTI metrics during MFR were examined; therefore, values of
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured
      in a population of 17 paraplegic dogs with naturally-occurring acute SCI showing
      MFR within 4 weeks after surgical decompression and compared to 6 control dogs.
      MRI scans were performed preoperatively and 12 weeks after MFR was observed. DTI
      metrics were obtained at the lesion epicentre and one SC segment cranially and
      caudally. Variance analyses were performed to compare values between evaluated
      localizations in affected dogs and controls and between time points. Correlations
      between DTI metrics and clinical scores at follow-up examinations were assessed.
      RESULTS: Before surgery, FA values at epicentres were higher than caudally (p =
      0.0014) and control values (p = 0.0097); ADC values were lower in the epicentre
      compared to control values (p = 0.0035) and perilesional (p = 0.0448 cranially
      and p = 0.0433 caudally). In follow-up examinations, no significant differences
      could be found between DTI values from dogs showing MFR and control dogs. Lower
      ADC values at epicentres correlated with neurological deficits at follow-up
      examinations (r = - 0.705; p = 0.0023). CONCLUSIONS: Findings suggest that a
      tendency to the return of DTI values to the physiological situation after
      surgical decompression accompanies MFR after SCI in paraplegic dogs. DTI may
      represent a useful and objective clinical tool for follow-up studies examining in
      vivo SC recovery in treatment studies.

PMID- 30223851
TI  - Review and analysis of Chilean dental undergraduate education: curriculum
      composition and profiles of first year dental students.
AB  - BACKGROUND: In Chile, dentistry has become a very popular career choice for
      students, which has resulted in a substantial increase in both, the number of
      dental graduates and dental schools. Nonetheless, there is a need for change in
      the way dental schools select and educate their students to keep pace with the
      rapidly changing nature of societal needs and to tackle the marked health
      inequalities that exist in the country. The aim of this study was to review and
      critique dental undergraduate education in Chile, with a particular focus on the
      curriculum composition and profiles of students admitted to dental schools from
      2010 to 2014. METHODS: A descriptive and retrospective design was utilised. Two
      different methods were undertaken: primary data collection regarding curriculum
      and secondary data analysis in relation to students' profiles. Descriptive
      statistics were used to assess the relative proportions of subject modules within
      the undergraduate dental curriculum and in particular the public health
      components. The analysis of the student profiles described specific background
      factors, namely, gender, age, secondary school type, location, rural-urban status
      and student's year of admission. Also, trends of dental students' intake between
      2010 and 2014 were investigated. Logistic regression analysis was undertaken to
      assess potential associations between the aforementioned background factors and
      students' choice of dental school. RESULTS: Regarding the curriculum review, a
      67% response rate was obtained. The most dominant component of Chilean dental
      curriculum was the clinical subjects (33%), followed by the basic and biological
      sciences (16%) and then medical and dental sciences (13%). In relation to the
      admission of students, the majority attended private schools (72%); most were
      females (62%); aged 19 years or less (74%); had an urban origin (99%); and came
      from subsidised private secondary schools (48%). Significant differences were
      found between students admitted to traditional and private dental schools.
      CONCLUSIONS: Clinical sciences are the most dominant subjects in the Chilean
      dental curriculum. Overall, traditional and private institutions had a broadly
      similar composition in their curriculum with the exception of the public health
      component. Students from disadvantaged backgrounds were the minority in dental
      schools across Chile.

PMID- 30223850
TI  - Screening and identification of B-cell epitopes within envelope protein of
      tembusu virus.
AB  - BACKGROUND: Tembusu virus is a newly emerging flavivirus that caused egg-drop
      syndrome in ducks in China. TMUV envelope protein is a major structural protein
      locates at the surface of tembusu virus particle. During tembusu virus infection,
      envelope protein plays a pivotal role in induction of neutralizing antibody.
      However, B cell epitopes within envelope protein have not been well studied.
      METHOD: A series of 13 peptides derived from E protein of tembusu virus were
      synthesized and screened by Dot blot with tembusu virus-positive duck serum.
      Potential B-cell epitopes were respectively fused with GST tag and expressed in
      E. coli. The immunogenicity and protective efficiency of epitopes were assessed
      in ducks. RESULTS: Dot blot assay identified the peptides P21 (amino acids 301
      329), P23 (amino acids 369-387), P27 (amino acids 464-471) and P28 (amino acids
      482-496) as potential B-cell epitopes within the envelope protein of tembusu
      virus. Immunization of prokaryotically expressed epitopes elicited specific
      antibodies in ducks and the specific antibody elicited by P21, P27 and P28 could
      neutralized tembusu virus. In addition, protective test suggested that P21 and
      P27 could completely protect immunized ducks from TMUV challenge. CONCLUSION:
      Four potential B cell epiotpes within tembusu virus envelope protein were
      identified and analyzed in vitro and in vivo. It was demonstrated that two of
      them (P21 and P27) could elicit neutralizing antibodies in ducks and offer
      complete protection against tembusu virus challenge. This findings will
      contribute to the development of epitope vaccine for tembusu virus prevention.

PMID- 30223852
TI  - Comparison of three diagnostic methods (microscopy, RDT, and PCR) for the
      detection of malaria parasites in representative samples from Equatorial Guinea.
AB  - BACKGROUND: Malaria in Equatorial Guinea remains a major public health problem.
      The country is a holo-endemic area with a year-round transmission pattern. In
      2016, the prevalence of malaria was 12.09% and malaria caused 15% of deaths among
      children under 5 years. In the Continental Region, 95.2% of malaria infections
      were Plasmodium falciparum, 9.5% Plasmodium vivax, and eight cases mixed
      infection in 2011. The main strategy for malaria control is quick and accurate
      diagnosis followed by effective treatment. Early and accurate diagnosis of
      malaria is essential for both effective disease management and malaria
      surveillance. The quality of malaria diagnosis is important in all settings, as
      misdiagnosis can result in significant morbidity and mortality. Microscopy and
      RDTs are the primary choices for diagnosing malaria in the field. However, false
      negative results may delay treatment and increase the number of persons capable
      of infecting mosquitoes in the community. The present study analysed the
      performance of microscopy and RDTs, the two main techniques used in Equatorial
      Guinea for the diagnosis of malaria, compared to semi-nested multiplex PCR (SnM
      PCR). RESULTS: A total of 1724 samples tested by microscopy, RDT, and SnM-PCR
      were analysed. Among the negative samples detected by microscopy, 335 (19.4%)
      were false negatives. On the other hand, the negative samples detected by RDT,
      128 (13.3%) were false negatives based on PCR. This finding is important,
      especially since it is a group of patients who did not receive antimalarial
      treatment. CONCLUSIONS: Owing to the high number of false negatives in
      microscopy, it is necessary to reinforce training in microscopy, the "Gold
      Standard" in endemic areas. A network of reference centres could potentially
      support ongoing diagnostic and control efforts made by malaria control programmes
      in the long term, as the National Centre of Tropical Medicine currently supports
      the National Programme against Malaria of Equatorial Guinea to perform all of the
      molecular studies necessary for disease control. Taking into account the results
      obtained with the RDTs, an exhaustive study of the deletion of the hrp2 gene must
      be done in EG to help choose the correct RDT for this area.

PMID- 30223853
TI  - Heterogeneous combinatorial expression of Hoxd genes in single cells during limb
      development.
AB  - BACKGROUND: Global analyses of gene expression during development reveal specific
      transcription patterns associated with the emergence of various cell types,
      tissues, and organs. These heterogeneous patterns are instrumental to ensure the
      proper formation of the different parts of our body, as shown by the phenotypic
      effects generated by functional genetic approaches. However, variations at the
      cellular level can be observed within each structure or organ. In the developing
      mammalian limbs, expression of Hox genes from the HoxD cluster is differentially
      controlled in space and time, in cells that will pattern the digits and the
      forearms. While the Hoxd genes broadly share a common regulatory landscape and
      large-scale analyses have suggested a homogenous Hox gene transcriptional
      program, it has not previously been clear whether Hoxd genes are expressed
      together at the same levels in the same cells. RESULTS: We report a high degree
      of heterogeneity in the expression of the Hoxd11 and Hoxd13 genes. We analyzed
      single-limb bud cell transcriptomes and show that Hox genes are expressed in
      specific combinations that appear to match particular cell types. In cells giving
      rise to digits, we find that the expression of the five relevant Hoxd genes
      (Hoxd9 to Hoxd13) is unbalanced, despite their control by known global enhancers.
      We also report that specific combinatorial expression follows a pseudo-time
      sequence, which is established based on the transcriptional diversity of limb
      progenitors. CONCLUSIONS: Our observations reveal the existence of distinct
      combinations of Hoxd genes at the single-cell level during limb development. In
      addition, we document that the increasing combinatorial expression of Hoxd genes
      in this developing structure is associated with specific transcriptional
      signatures and that these signatures illustrate a temporal progression in the
      differentiation of these cells.

PMID- 30223854
TI  - Dietary diversity feeding practice and its associated factors among children age
      6-23 months in Ethiopia from 2011 up to 2018: a systematic review and meta
      analysis.
AB  - BACKGROUND: Globally Less than one fourth of children aged 6-23 months get the
      recommended minimum dietary diversity feeding practice. Despite this issue is
      common in Ethiopia, fragmented and inconsistent findings were found. Therefore
      the main objective of this meta-analysis was to estimate the pooled prevalence of
      dietary diversity feeding practice and to identify its associated factors among
      children aged 6-23 months in Ethiopia. METHODS: The Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guideline was followed. Articles were
      systematically searched through PubMed, Google scholar, Google, Hinari and
      Cochrane library. Newcastle-Ottawa Scale adapted for cross-sectional studies
      quality assessment tool was used to assess the quality of each study. A total of
      14 studies were extracted and analyzed using STATA 14. Random effect model was
      used to estimate the pooled prevalence; whereas subgroup analysis and meta
      regression was performed to identify the probable source of heterogeneity. Both
      egger's and begg's test were used to check publication bias. Furthermore, the
      effect between associated factor variables, and dietary diversity feeding
      practices were examined. RESULTS: A total of 154 studies were retrieved and 14
      studies were included in meta-analysis. The Meta analysis result showed that the
      pooled prevalence of dietary feeding practice among children age 6-23 months in
      Ethiopia was 23.25% with considerable heterogeneity (I2 = 98.8, p = 0.00). In the
      subgroup analysis, the lowest prevalence was observed in Amhara region (12.58%).
      Home delivery OR: 0.63, antenatal care follow up OR: 1.80, postnatal care visit
      OR: 2.61, mothers decision making status OR: 1.65, mothers media exposure status
      OR: 2.79 and being urban residence OR: 2.18 (1.26, 3.77) were significant factors
      for minimum dietary diversity feeding practice in Ethiopia. CONCLUSIONS: The
      pooled prevalence of dietary diversity feeding practice among children aged 6-23
      months in Ethiopia was low. Place of delivery, post natal care, antenatal care
      service, mothers decision making status, mothers media exposure status and being
      urban residence were found to be the significant factors.

PMID- 30223855
TI  - Recently resettled refugee women-at-risk in Australia evidence high levels of
      psychiatric symptoms: individual, trauma and post-migration factors predict
      outcomes.
AB  - BACKGROUND: Despite increasing numbers of refugee women-at-risk being resettled
      and their potential vulnerability, there exists no empirical research into the
      psychiatric health of this unique subgroup with which to guide policy and
      practice. This research aimed to investigate psychiatric symptom status of a
      sample of refugee women-at-risk recently resettled in Australia, as well as
      factors contributing to symptoms of trauma, anxiety, depression, and
      somatization. The level of psychiatric symptomatology is compared to reference
      groups of women from Sudan and Burma, who entered Australia under the
      Humanitarian Entry Programme, and who did not meet criteria as women-at-risk.
      METHODS: This is a cross-sectional survey of 104 refugee women-at-risk across
      several ethnic groups including a demographic questionnaire, the Harvard Trauma
      Questionnaire, Post-migration Living Difficulties Checklist, and Hopkins Symptom
      Checklist to assess individual factors, traumatic experiences, post-migration
      problems, and symptoms of trauma, anxiety, depression, and somatization. A series
      of multiple hierarchical regression analyses examined factors predicting
      psychiatric symptoms. RESULTS: Substantial proportions of participants reported
      psychiatric distress in symptomatic ranges, including for traumatization (41%),
      post-traumatic stress disorder (20%), anxiety (29%), and depression (41%), as
      well as significant symptoms of somatization (41%). These findings are
      significantly higher than those derived from reference groups of women from Sudan
      or Burma, resettled in the same area and utilizing a similar methodology. Higher
      numbers of trauma events and post-migration living difficulties predicted higher
      trauma, depression, and somatic (but not anxiety) symptoms. Having children
      predicted higher trauma, anxiety, and somatic symptoms. Greater English fluency
      predicted higher anxiety symptoms. Region of birth predicted anxiety and
      depression symptoms. Age predicted trauma and anxiety symptoms. CONCLUSIONS:
      Findings suggest that recently arrived refugee women-at-risk are at high risk of
      psychiatric disorders. The results indicate a need for comprehensive psychiatric
      assessment to identify women in need of treatment very early after resettlement,
      with implications for medical practice, service delivery, and policy programs.

PMID- 30223856
TI  - Zootherapeutic uses of wildmeat and associated products in the semiarid region of
      Brazil: general aspects and challenges for conservation.
AB  - BACKGROUND: Hunting wildlife for medicinal purposes is a widespread practice
      throughout Brazil; however, studies about the animals used for zootherapeutic
      practices have been performed almost exclusively with traders (herbalists) and
      end consumers, and not hunters. This makes it difficult to completely understand
      the market chain, trade strategies, and drivers of this practice. The present
      study investigated the species hunted or trapped for traditional medicinal uses
      by collecting data about the use and trade of the zootheurapeutic species.
      METHODS: We collected data through semi-structured questionnaires complemented by
      free interviews and informal conversations with hunters in five municipalities of
      semiarid region of the NE Brazil. We calculated the Use-Value (UV) index to
      determine the relative importance of each species reported by interviewees. The
      Multiple Linear Regression model was used to assess the influence of
      socioeconomic factors (age, schooling, residence zone, trade of zootherapeutic
      species) on species richness exploited by hunters. RESULTS: Hunters reported a
      significant richness of species (n = 39) intentionally or opportunistically
      captured for use as remedies for treatment of 92 diseases or conditions in humans
      or livestock. Respondents also reported trade strategies that were well-organized
      and quickly directed the selling of wild animals or byproducts via modern
      technology. We found a weak positive relationship only between species richness
      and hunters' age via MLR model. CONCLUSIONS: The hunting and use of wild species
      for medicinal purposes are culturally disseminated activities among hunters. Our
      results demonstrate the importance of studying hunters in order to understanding
      the dynamics of bushmeat exploitation and to develop more efficient strategies
      for wildlife use and conservation.

PMID- 30223857
TI  - A remote EPID-based dosimetric TPS-planned audit of centers for clinical trials:
      outcomes and analysis of contributing factors.
AB  - BACKGROUND: A novel remote method for external dosimetric TPS-planned auditing of
      intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy
      (VMAT) for clinical trials using electronic portal imaging device (EPID) has been
      developed. The audit has been applied to multiple centers across Australia and
      New Zealand. This work aims to assess the audit outcomes and explores the
      variables that contributed to the audit results. METHODS: Thirty audits were
      performed of 21 radiotherapy facilities, 17 facilities underwent IMRT audits and
      13 underwent VMAT audits. The assessment was based on comparisons between the
      delivered doses derived from images acquired with EPIDs and planned doses from
      the local treatment planning systems (TPS). Gamma pass-rate (GPR) and gamma mean
      value (GMV) were calculated for each IMRT field and VMAT arc (total 268
      comparisons). A multiple variable linear model was applied to the GMV results
      (3%/3 mm criteria) to assess the influence and significance of explanatory
      variables. The explanatory variables were Linac-TPS combination, TPS grid
      resolution, IMRT/VMAT delivery, age of EPID, treatment site, record and
      verification system (R&V) type and dose-rate. Finally, the audit results were
      compared with other recent audits by calculating the incidence ratio (IR) as a
      ratio of the observed mean/median GPRs for the remote audit to the other audits.
      RESULTS: The average (+/- 1 SD) of the centers' GPRs were: 99.3 +/- 1.9%, 98.6 +/
      2.7% & 96.2 +/- 5.5% at 3%, 3 mm, 3%, 2 mm and 2%, 2 mm criteria respectively.
      The most determinative variables on the GMVs were Linac-TPS combination, TPS grid
      resolution and IMRT/VMAT delivery type. The IR values were 1 for seven
      comparisons, indicating similar GPRs of the remote audit with the reference
      audits and > 1 for four comparisons, indicating higher GPRs of the remote audit
      than the reference audits. CONCLUSION: The remote dosimetry audit method for
      clinical trials demonstrated high GPRs and provided results comparable to
      established more resource-intensive audit methods. Several factors were found to
      influence the results including some effect of Linac-TPS combination.

PMID- 30223858
TI  - TMJ pathomorphology in patients with JIA-radiographic parameters for early
      diagnosis.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is often accompanied by
      pathomorphological changes to the temporomandibular joint (TMJ). By analyzing
      orthodontical orthopantomograms of JIA patients the aims of the study were a)
      classification of condyle changes, b) quantification of bony asymmetries of
      condylar destruction and c) detection of relationships between disease duration
      and TMJ-involvement. PATIENTS/METHODS: 46 caucasian JIA-patients (28 female; 18
      male; < 16.0 years) were enrolled, each joint (n = 92) was morphologically
      assessed by means of orthopantomogram, quantitatively analysed and compared with
      duration of general disease. Condyle morphology was assessed using the Billiau
      scale for severity of destruction [1]. The quantitative analysis was based on
      ratios of condyle, ramus and mandible height. RESULTS: Patients were divided into
      groups (Group I - slightly affected, n = 36; Billiau severity 0-2; condyle
      findings: X-ray normal, condyle erosions, condylar flattening; Group II -
      severely affected, N = 10; Billiau severity 3-4; condyle findings: condylar
      flattenings and erosions, unilateral/bilateral complete loss of condyles), based
      on morphological analysis of condylar destruction. Duration of disease was
      significantly longer in Group II (8.9 +/- 5.2 years) than in Group I (4.6 +/- 4.7
      years). Asymmetries of condyle, ramus and mandible height, quantitatively
      analysed by contralateral comparison, were significantly more marked in patients
      of Group II than of Group I. CONCLUSIONS: Orthopantomogram imaging can be used in
      orthodontics clinical routine to detect TMJ-pathologies and is an important
      reference for monitoring progression of JIA. Classification into severe and
      slightly affected TMJ is possible by analysis of condylar pathomorphology. An
      association between degree of destruction, extent of lower jaw asymmetry and
      disease duration is suggested by the results.

PMID- 30223859
TI  - First establishment of a new table-rotated-type hybrid emergency room system.
AB  - The hybrid emergency room (hybrid ER) system was first established in 2011 in
      Japan. It is defined as an integrated system including an ER, emergency computed
      tomography (CT) and interventional radiology (IVR) rooms, and operating rooms.
      Severe trauma patients can undergo emergency CT examinations and therapies
      (surgeries) without being transferred. The hybrid ER system is attracting
      attention because trauma resuscitation using this system has been reported to
      potentially improve the mortality rate in severe trauma patients. In August 2017,
      we established a new table-rotated-type hybrid ER to facilitate surgical
      functions. Herein, we introduce a new table-rotated-type hybrid ER consisting of
      an IVR-CT-operating room system and discuss its efficiency and feasibility for
      trauma resuscitation, including surgery and IVR. This system includes four new
      concepts: (1) to secure a wide working space during trauma resuscitation by
      reconsidering the arrangement of the C-arm, (2) ensure an air-conditioned
      operating room in the hybrid ER, (3) adopt an operating table but not
      interventional radiology table, and (4) prepare a trauma bay with three
      additional beds for multiple victims. This hybrid ER system also adopted the
      rotated-type table to secure a wide working space during the resuscitation phase.
      The C-arm was located away from the patients and placed on the wall opposite to
      the CT gantry, in contrast to that in previous systems. If patients needed an
      emergency IVR, the table was just rotated, and the IVR could be conducted
      immediately. This improvement can secure a wide working space in the hybrid ER.
      Moreover, the patient table was also a surgical operating table, and the hybrid
      ER system had an air-conditioned operating room (class 10,000). In the
      anticipation of many trauma patients being transported to the ER, a new trauma
      bay with three additional beds next to the hybrid ER was established, which also
      had an air-conditioned operating room. This new rotated-type hybrid ER system
      facilitates efficient surgical functions during trauma resuscitation and can
      secure a wide working space for the medical team to immediately perform
      resuscitative procedures and IVRs without delay.

PMID- 30223860
TI  - Environmental suitability for lymphatic filariasis in Nigeria.
AB  - BACKGROUND: Lymphatic filariasis (LF) is a mosquito-borne parasitic disease and a
      major cause of disability worldwide. It is one of the neglected tropical diseases
      identified by the World Health Organization for elimination as a public health
      problem by 2020. Maps displaying disease distribution are helpful tools to
      identify high-risk areas and target scarce control resources. METHODS: We used
      pre-intervention site-level occurrence data from 1192 survey sites collected
      during extensive mapping surveys by the Nigeria Ministry of Health. Using an
      ensemble of machine learning modelling algorithms (generalised boosted models and
      random forest), we mapped the ecological niche of LF at a spatial resolution of 1
      km2. By overlaying gridded estimates of population density, we estimated the
      human population living in LF risk areas on a 100 * 100 m scale. RESULTS: Our
      maps demonstrate that there is a heterogeneous distribution of LF risk areas
      across Nigeria, with large portions of northern Nigeria having more
      environmentally suitable conditions for the occurrence of LF. Here we estimated
      that approximately 110 million individuals live in areas at risk of LF
      transmission. CONCLUSIONS: Machine learning and ensemble modelling are powerful
      tools to map disease risk and are known to yield more accurate predictive models
      with less uncertainty than single models. The resulting map provides a
      geographical framework to target control efforts and assess its potential
      impacts.

PMID- 30223862
TI  - Description of 22 new alpha-1 antitrypsin genetic variants.
AB  - Alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder caused by
      mutations of the highly polymorphic SERPINA1 gene. This genetic disorder still
      remains largely under-recognized and can be associated with lung and/or liver
      injury. The laboratory testing for this deficiency typically comprises serum
      alpha-1 antitrypsin quantification, phenotyping according to the isoelectric
      focusing pattern and genotyping if necessary. To date, more than 100 SERPINA1
      variants have been described and new genetic variants are frequently discovered.
      Over the past 10 years, 22 new genetic variants of the SERPINA1 gene were
      identified in the daily practice of the University Medical laboratories of Lille
      and Lyon (France). Among these 22 variants, seven were Null alleles and one with
      a M1 migration pattern (M1Cremeaux) was considered as deficient according to the
      clinical and biological data and to the American College of Medical Genetics and
      Genomics (ACMG) criteria. Three other variants were classified as likely
      pathogenic, three as variants of uncertain significance while the remaining ones
      were assumed to be neutral. Moreover, we also identified in this study two
      recently described SERPINA1 deficient variants: Trento (p.Glu99Val) and SDonosti
      (p.Ser38Phe). The current data, together with a recent published meta-analysis,
      represent the most up-to-date list of SERPINA1 variants available so far.

PMID- 30223863
TI  - Treatment of 503 cattle with traumatic reticuloperitonitis.
AB  - BACKGROUND: The treatment of traumatic reticuloperitonitis (TRP) in cattle has a
      long and impressive history that goes back more than 100 years. This study
      describes treatment for TRP in 503 cattle. Initial treatment was based on
      radiographic findings; cattle with a foreign body attached to a magnet were
      treated conservatively using antibiotics, anti-inflammatory drugs and intravenous
      fluids. Cattle with a foreign body lying on the ventral aspect of the reticulum
      or penetrating or perforating the reticulum received a magnet in addition to
      medical treatment. Cattle were radiographed again the next day. When the foreign
      body was completely attached to the magnet, medical treatment was continued. When
      the foreign body was not attached or still penetrated/perforated the reticulum, a
      rumenotomy was carried out. RESULTS: Of the 503 cattle, 232 were treated
      conservatively, 206 underwent surgery, 61 were slaughtered or euthanased and four
      were treated after discharge at home with a magnet and antibiotics. Surgical
      treatment was significantly more successful than conservative treatment; 90% of
      206 operated and 82% of 232 medically-treated cattle were discharged.
      CONCLUSIONS: For practical purposes, cattle suspected of having traumatic
      reticuloperitonitis should initially be treated with a magnet and antibiotics and
      re-evaluated, ideally radiographically, when response to treatment does not occur
      within 3 or 4 days. Surgery is limited to cases in which the foreign body fails
      to completely attach to the magnet.

PMID- 30223864
TI  - Deep sequencing of SMPD1 gene revealed a heterozygous frameshift mutation
      (p.Ser192Alafs) in a Palestinian infant with Niemann-Pick disease type A: a case
      report.
AB  - BACKGROUND: Niemann-Pick disease is caused by reduced level of the lysosomal
      enzyme acid sphingomyelinase. Children can survive between 2 and 12 years based
      on the disease type. Two main types are well known: type A and B. Niemann-Pick
      disease type A is characterized by severe central nervous system deterioration
      and hepatosplenomegaly while type B is a progressive hypersplenism accompanied
      with gradual deterioration of pulmonary function. CASE PRESENTATION: We describe
      an 11-month-old Palestinian baby boy with hepatosplenomegaly, hypotonia, delayed
      motor development, laryngomalacia, bilateral cherry-red spots, and failure to
      thrive. Metabolic screening, blood count, differential tests, immunology screen,
      infectious disease screen, urine, biochemical tests as well as molecular
      diagnosis were performed. The molecular diagnosis was done by amplifying the
      whole sphingomyelin phosphodiesterase 1 (SMPD1) gene, followed by deep
      sequencing. The obtained sequences were aligned, de novo assembled and compared
      to human reference gene (GenBank GeneID: NG_011780.1, Ensembl version
      ENSG00000166311 and protein identified as UniProtKB - P17405). Two known
      mutations were identified in our patient: the pathogenic frameshift mutation
      NM_000543.4(SMPD1):c.573delT (p.Ser192Alafs) and the benign polymorphism
      NM_000543.4(SMPD1):c.107T>C (p.Val36Ala). The enzyme study showed a very low
      level of enzymatic activity of acidic sphingomyelinase (0.1 nmol/ml per hour).
      Correlations between clinical findings, laboratory data, and sequence analysis
      are presented. CONCLUSIONS: In conclusion, this is the first report about a
      heterozygote frameshift p.Ser192AlafsX65 in a Palestinian patient with Niemann
      Pick disease type A, emphasizing the importance of deep sequencing in genetic
      diagnosis of this rare inherited disease.

PMID- 30223865
TI  - Bronchopneumonia in Swedish lambs: a study of pathological changes and
      bacteriological agents.
AB  - BACKGROUND: One of the most common post-mortem inspection finding of sheep and
      lambs in Sweden, following routine slaughter is pneumonia and its prevalence is
      increasing. To our knowledge, the aetiology of pneumonia in lambs is not well
      known for Swedish conditions. Chronic bronchopneumonia, also known as "atypical"
      or chronic non-progressive pneumonia, is a common disease worldwide, affecting
      lambs up to 12 months old. It is therefore of interest to elucidate if this
      disease complex is also a common cause of pneumonia among Swedish lambs. Chronic
      bronchopneumonia has a characteristic macroscopic and histopathologic appearance,
      and Mycoplasma ovipneumoniae is the microbial agent most frequently found.
      Although this bacterium is important for the pathogenesis, multiple agents are
      presumed to be involved. The aim of this study was to describe the macroscopic
      and histopathologic lung lesions in routinely slaughtered lambs with pneumonia,
      and to determine the bacterial agents involved. RESULTS: A total of 41 lungs with
      gross lesions consistent with pneumonia were examined. Of these, 35 lungs
      displayed the typical gross appearance of chronic bronchopneumonia, with several
      or all of the characteristic histological features. M. ovipneumoniae was detected
      in 83% of the 35 lungs and Mannheimia haemolytica was isolated in 71%. Pneumonia
      associated with M. ovipneumoniae could be correlated to specific gross lesions
      consistent with the gross description of chronic bronchopneumonia in lambs.
      CONCLUSION: In this study, chronic bronchopneumonia was the most common lung
      disease in routinely slaughtered Swedish lambs. This diagnosis was based on the
      characteristic macroscopic and histopathologic pulmonary findings and the
      frequent presence of the bacterium M. ovipneumoniae. The macroscopic appearance
      of chronic bronchopneumonia could therefore be used during routine investigation
      of the lamb carcasses at slaughter, to determine the most likely cause of
      pneumonia.

PMID- 30223861
TI  - Long non-coding RNAs in esophageal cancer: molecular mechanisms, functions, and
      potential applications.
AB  - Esophageal cancer (EC) is the sixth leading cause of cancer-related death
      worldwide. The lack of early diagnostic biomarkers and effective prognostic
      indicators for metastasis and recurrence has resulted in the poor prognosis of
      EC. In addition, the underlying molecular mechanisms of EC development have yet
      to be elucidated. Accumulating evidence has demonstrated that lncRNAs play a
      vital role in the pathological progression of EC. LncRNAs may regulate gene
      expression through the recruitment of histone-modifying complexes to the
      chromatin and through interactions with RNAs or proteins. Recent evidence has
      demonstrated that the dysregulation of lncRNAs plays important roles in the
      proliferation, metastasis, invasion, angiogenesis, apoptosis, chemoradiotherapy
      resistance, and stemness of EC, which suggests potential clinical implications.
      In this review, we highlight the emerging roles and regulatory mechanisms of
      lncRNAs in the context of EC and discuss their potential clinical applications as
      diagnostic and prognostic biomarkers.

PMID- 30223866
TI  - Non-classical 11beta-hydroxylase deficiency caused by compound heterozygous
      mutations: a case study and literature review.
AB  - BACKGROUND: 11beta-hydroxylase deficiency (11OHD) is extremely rare, and reports
      of non-classical 11OHD are even rarer. Non-classical 11OHD usually presents as
      premature adrenarche, hyperandrogenism, menstrual disorders, and hypertension.
      Because the symptoms of non-classical 11OHD are mild, delayed diagnosis or
      misdiagnosis as polycystic ovary syndrome or primary hypertension is common. CASE
      PRESENTATION: This paper introduces a case of a young female patient presenting
      hypertension and menstrual disorders. Laboratory examination revealed increased
      androgen levels, mild adrenal hyperplasia, mild left ventricular hypertrophy, and
      mild sclerosis of the lower limb arteries. 11OHD was confirmed by genetic
      testing, and the patient was found to carry compound heterozygous mutations in
      CYP11B1 (c.583 T > C and c.1358G > A). The mutation Y195H is located in exon 3
      and has not been reported previously. In silico studies indicated that this
      mutation may cause reduced enzymatic activity. After treatment with
      hydrocortisone and spironolactone, blood pressure was brought under good control,
      and menstruation returned to normal. We also conducted a retrospective review of
      previously reported cases in the literature (over 170 cases since 1991).
      CONCLUSIONS: Early diagnosis of non-classical 11OHD is difficult because its
      symptoms are mild. The possibility of this disease should be considered in
      patients with early-onset hypertension, menstrual disorders, and hyperandrogenism
      to provide early treatment and prevent organ damage due to hypertension and
      hyperandrogenism. CYP11B1 mutations are known to be race-specific and are
      concentrated in exons 3 and 8, of which mutations in the former are mostly
      associated with non-classical 11OHD, whereas mutations in the latter are mostly
      found in classical 11OHD, characterized by severe loss of enzymatic activity.

PMID- 30223867
TI  - Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c
      oxidase.
AB  - BACKGROUND: Treatment of heart failure remains one of the most challenging task
      for intensive care medicine, cardiology and cardiac surgery. New options and
      better indicators are always required. Understanding the basic mechanisms
      underlying heart failure promote the development of adjusted therapy e.g. assist
      devices and monitoring of recovery. If cardiac failure is related to compromised
      cellular respiration of the heart, remains unclear. Myocardial respiration
      depends on Cytochrome c- Oxidase (CytOx) activity representing the rate limiting
      step for the mitochondrial respiratory chain. The enzymatic activity as well as
      mRNA expression of enzyme's mitochondrial encoded catalytic subunit 2, nuclear
      encoded regulatory subunit 4 and protein contents were studied in biopsies of
      cardiac patients suffering from myocardial insufficiency and dilated
      cardiomyopathy (DCM). METHODS: Fifty-four patients were enrolled in the study and
      underwent coronary angiography. Thirty male patients (mean age: 45 +/- 15 yrs.)
      had a reduced ejection fraction (EF) 35 +/- 12% below 45% and a left ventricular
      end diastolic diameter (LVEDD) of 71 +/- 10 mm bigger than 56 mm. They were
      diagnosed as having idiopathic dilated cardiomyopathy (DCM) without coronary
      heart disease and NYHA-class 3 and 4. Additionally, 24 male patients (mean age:
      52 +/- 11 yrs.) after exclusion of secondary cardiomyopathies, coronary artery or
      valve disease, served as control (EF: 68 +/- 7, LVEDD: 51 +/- 7 mm). Total RNA
      was extracted from two biopsies of each person. Real-time PCR analysis was
      performed with specific primers followed by a melt curve analysis. Corresponding
      protein expression in the tissue was studied with immune-histochemistry while
      enzymatic activity was evaluated by spectroscopy. RESULTS: Gene and protein
      expression analysis of patients showed a significant decrease of subunit 4 (1.1
      vs. 0.6, p < 0.001; 7.7 +/- 3.1% vs. 2.8 +/- 1.4%, p < 0.0001) but no differences
      in subunit 2. Correlations were found between reduced subunit 2 expression, low
      EF (r = 0.766, p < 0.00045) and increased LVEDD (r = 0.492, p < 0.0068). In case
      of DCM less subunit 4 expression and reduced shortening fraction (r = 0.524, p <
      0.017) was found, but enzymatic activity was higher (0.08 +/- 0.06 vs. 0.26 +/-
      0.08 U/mg, p < 0.001) although myocardial oxygen consumption continued to the
      same extent. CONCLUSION: In case of myocardial insufficiency and DCM, decreased
      expression of COX 4 results in an impaired CytOx activity. Higher enzymatic
      activity but equal oxygen consumption contribute to the pathophysiology of the
      myocardial insufficiency and appears as an indicator of oxidative stress. This
      kind of dysregulation should be in the focus for the development of diagnostic
      and therapy procedures.

PMID- 30223869
TI  - Apatinib for patients with advanced or recurrent cervical cancer: study protocol
      for an open-label randomized controlled trial.
AB  - BACKGROUND: In China, cervical cancer is the fifth most commonly diagnosed
      cancer, and the outcomes for patients with advanced or recurrent disease are
      poor. Apatinib, a small molecule inhibitor of vascular endothelial growth factor
      receptor (VEGFR-2), is an orally bioavailable agent, which has shown survival
      benefit in multiple solid tumors. Based on previous research, this phase II
      clinical trial aims to verify apatinib's efficacy and safety in patients with
      advanced or recurrent cervical cancer. METHODS/DESIGN: This randomized, parallel
      arm, open-label, interventional trial will be carried out to evaluate the
      efficacy and the safety of apatinib for advanced or recurrent cervical cancer. A
      total of 60 eligible patients will be allocated by intention, in a ratio of 1:1,
      to either the experimental group or the control group. The primary endpoint is
      progression-free survival, the secondary endpoints include overall survival,
      disease control rate, objective response rate, quality of life, and adverse
      events. Assessments will be carried out before enrolment (baseline) and every 4
      weeks after treatment. DISCUSSION: The aim of this trial is to demonstrate the
      clinical effect, safety, and side effects of apatinib in the treatment of
      advanced or recurrent cervical cancer. This study will clarify the efficacy and
      safety of this regimen. TRIAL REGISTRATION: Chinese Clinical Trials Registry,
      ChiCTR-OIN-17012164 . Registered on 24 July 2017.

PMID- 30223868
TI  - Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures
      and reduces stroke damage via the sigma 1 receptor.
AB  - Cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis
      sativa plant, exhibits therapeutic potential for various human diseases,
      including chronic neurodegenerative diseases, such as Alzheimer's and
      Parkinson's, ischemic stroke, epilepsy and other convulsive syndromes,
      neuropsychiatric disorders, neuropathic allodynia and certain types of cancer.
      CBD does not bind directly to endocannabinoid receptors 1 and 2, and despite
      research efforts, its specific targets remain to be fully identified. Notably,
      sigma 1 receptor (sigma1R) antagonists inhibit glutamate N-methyl-D-aspartate
      acid receptor (NMDAR) activity and display positive effects on most of the
      aforesaid diseases. Thus, we investigated the effects of CBD on three animal
      models in which NMDAR overactivity plays a critical role: opioid analgesia
      attenuation, NMDA-induced convulsive syndrome and ischemic stroke. In an in vitro
      assay, CBD disrupted the regulatory association of sigma1R with the NR1 subunit
      of NMDAR, an effect shared by sigma1R antagonists, such as BD1063 and
      progesterone, and prevented by sigma1R agonists, such as 4-IBP, PPCC and PRE084.
      The in vivo administration of CBD or BD1063 enhanced morphine-evoked supraspinal
      antinociception, alleviated NMDA-induced convulsive syndrome, and reduced the
      infarct size caused by permanent unilateral middle cerebral artery occlusion.
      These positive effects of CBD were reduced by the sigma1R agonists PRE084 and
      PPCC, and absent in sigma1R-/- mice. Thus, CBD displays antagonist-like activity
      toward sigma1R to reduce the negative effects of NMDAR overactivity in the
      abovementioned experimental situations.

PMID- 30223871
TI  - Nutrient consumption and associated factors among school age children in Dewa
      Chefe District, northeast Ethiopia: a cross-sectional study.
AB  - BACKGROUND: Inadequate nutrient consumption causes protein energy malnutrition
      and micronutrient deficiencies and related consequences, including poor physical
      growth and intellectual development. However, literatures showing quantitative
      measurement of dietary intake of children are limited in Ethiopia. Therefore,
      this study investigated nutrient consumption and associated factors among school
      age children (7-9 years) in Dewa Cheffe District, northeast of Ethiopia. METHODS:
      A community based cross-sectional study was conducted from November to December,
      2015 in Dewa Cheffe District. A multistage sampling technique was used to select
      605 study subjects. Pre-tested and structured questionnaire was used to collect
      data. A 24-h dietary recall with portion size estimation method was used to
      assess nutrient consumption of school age children. Multivariable logistic
      regression analysis was fitted to identify factors associated with inadequate
      energy intake. adjusted odds ratio (AOR) with corresponding 95% confidence
      interval was computed to show the strength of association. In multivariable
      analysis, a P value of < 0.05 was used to declare statistically significance.
      RESULTS: A total of 600 school age children were included in the study. About 29%
      [95%, CI 21.9, 36.1] of study participants had inadequate energy intake. The
      result of multivariable analysis revealed that, children who were belonged to a
      female headed households [AOR = 3.65; 95% CI 1.20, 11.04] and family size of six
      and above [AOR = 14.42; 95% CI 4.65, 44.67] were found with increased odds of
      inadequate energy consumption. In contrast, decreased odds of inadequate energy
      consumption were observed among children whose mothers were housewives [AOR =
      0.32; 95% CI 0.11, 0.52]. CONCLUSIONS: In this study, one-third of school
      children had inadequate energy consumption. Female headed households, being in
      the larger family size and housewives mother were significantly associated with
      inadequate energy consumption. Therefore, giving special focus to female headed
      households, large family and outdoor worker mothers will help to improve dietary
      intake of children.

PMID- 30223872
TI  - Unintended pregnancy and associated factors among pregnant women in Arsi Negele
      Woreda, West Arsi Zone, Ethiopia.
AB  - OBJECTIVE: The study was aimed at determining the prevalence of unintended
      pregnancy and associated factors in Arsi Negele Woreda from May 01, 2017 to July
      30, 2017. RESULTS: Unintended pregnancy was found to be 41.5%. The multivariable
      logistic regression revealed that 35 and above age group (AOR; 2.343, 95% CI
      1.374, 3.997), single marital status (AOR; 6.492, 95% CI 1.299, 32.455), parity
      of 2 (AOR; 53.419, 95% CI 21.453, 133.014), parity of 3 and above (AOR; 20.219,
      95% CI 7.915, 51.655), having abortion history (AOR; 1.962, 95% CI 1.025, 3.755),
      having health professional visit (AOR; 2.004, 95% CI 1.218, 3.298) and having
      autonomy to use contraceptive method (AOR; 2.925, 95% CI 1.648, 5.190) were
      significantly associated with unintended pregnancy. Therefore, reproductive
      health advocacy, counseling and access of modern contraceptive methods are
      recommended.

PMID- 30223870
TI  - Reducing disability via a family centered intervention for acutely ill persons
      with Alzheimer's disease and related dementias: protocol of a cluster-randomized
      controlled trial (Fam-FFC study).
AB  - BACKGROUND: Hospitalized older persons with Alzheimer's disease and related
      dementias are at greater risk for functional decline and increased care
      dependency after discharge due to a combination of intrinsic factors,
      environmental, policy, and care practices that restrict physical and cognitive
      activity, lack of family involvement and limited staff knowledge of dementia
      care. We have developed a theory-based intervention, Family centered Function
      focused Care, that incorporates an educational empowerment model for family
      caregivers (FCGs) provided within a social-ecological framework to promote
      specialized care to patients with dementia during hospitalization and the 60-day
      post-acute period. Primary aims are to test the efficacy of the intervention in
      improving physical and cognitive recovery in hospitalized persons living with
      Alzheimer's disease and related dementias (ADRD) and improving FCG preparedness
      and experiences. METHOD: We will implement Family centered Function-focused Care
      in a cluster-randomized trial of 438 patient/FCG dyads in six hospital units
      randomized within three hospitals. We hypothesize that patients who receive the
      intervention will demonstrate better physical function, less delirium occurrence
      and severity, neuropsychiatric symptoms, and depression compared to those in the
      control condition (Education-only). We also hypothesize that FCGs enrolled in
      Family centered Function-focused Care will experience increased preparedness for
      caregiving, and less strain, burden, and desire to institutionalize, as compared
      to FCGs the control group. We will also examine the costs and relative cost
      savings associated with the intervention and will evaluate the cultural
      appropriateness of Family centered Function-focused Care for families from
      diverse backgrounds. DISCUSSION: Our theory-based intervention makes use of real
      world applicable approaches in a novel and innovative way to change the paradigm
      of how we currently look at acute care and post-acute transitions in persons with
      ADRD. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03046121 . Registered on 8
      February 2017.

PMID- 30223873
TI  - An Internet-based Acceptance and Commitment Therapy intervention for older adults
      with anxiety complaints: study protocol for a cluster randomized controlled
      trial.
AB  - BACKGROUND: Anxiety is among the most prevalent and disabling mental health
      problems in older adults. Few older adults with mild to moderately severe anxiety
      symptoms receive adequate interventions, putting them at risk for developing
      anxiety disorders, depression, and various somatic problems. Effective, low
      threshold interventions should be developed. Blended care, in which a web-based
      intervention is combined with a limited amount of face-to-face contacts with a
      mental healthcare counselor at the general practice, is a promising option. The
      online self-help intervention "Living to the Full"-an Acceptance and Commitment
      Therapy (ACT) intervention-has been proven to reduce depression and anxiety in
      several patient groups, but has not yet been investigated in older adults. The
      aim of this study is to evaluate the (cost-)effectiveness of a blended form of
      "Living to the Full" in reducing anxiety symptoms in adults aged 55 to 75 years.
      Furthermore, moderators and mediators of the treatment effect are investigated.
      METHODS/DESIGN: The (cost-)effectiveness of the ACT intervention will be
      investigated in a cluster single-blind randomized controlled trial (RCT). The
      blended intervention will be compared to treatment-as-usual. Thirty-six mental
      health counselors working at general practices in the Netherlands will be
      randomized to deliver blended care or treatment as usual. A total of 240
      participants (aged 55-75 years) with mild to moderately severe anxiety complaints
      (defined as a total score of 5-15 on the GAD-7) will be recruited. There are four
      measurements consisting of online questionnaires (primary outcome: GAD-7) and a
      telephone interview: before the start of the intervention; directly following the
      intervention (14 weeks after baseline); and six and twelve months after baseline.
      Possible mediator variables will be assessed multiple times basis during the
      intervention. DISCUSSION: This RCT will evaluate the effectiveness of a blended
      ACT intervention for older adults with anxiety symptoms. If the intervention is
      shown to be effective, it will be implemented, thereby improving the
      accessibility and quality of preventive interventions for older adults with
      anxiety problems. TRIAL REGISTRATION: Netherlands Trial Register, NTR6270 .
      Registered on 21 March 2017.

PMID- 30223874
TI  - Evaluating the integration of HIV self-testing into low-resource health systems:
      study protocol for a cluster-randomized control trial from EQUIP Innovations.
AB  - BACKGROUND: Throughout sub-Saharan Africa HIV-testing rates remain low. Barriers
      to testing, such as inconvenient service hours and long wait times, lack of
      privacy, and fear of unwanted disclosure, continue to impede service utilization.
      HIV self-testing (HIVST) is one strategy that addresses these barriers and has
      been shown to increase use of HIV-testing when distributed through community
      based settings. However, the scalability of HIVST is limited because it has yet
      to be fully integrated into existing health systems and routine care. To address
      this gap, we designed a study to test the effect of offering HIVST to routine
      outpatient department (OPD) clients on uptake of HIV-testing as compared to
      standard of care and optimized standard of care. METHODS/DESIGN: This is a non
      blinded, multi-site, cluster-randomized control trial. The health facility is the
      unit of randomization (cluster). Fifteen facilities were randomized to one of
      three arms: (1) Standard of care using routine provider-initiated testing and
      counseling (PITC); (2) Optimized standard of care using optimized PITC defined by
      additional training, job aids, and monitoring of PITC strategies with OPD
      providers and support staff; and (3) HIVST defined by HIVST demonstrations for
      OPD clients, HIVST kit distribution, and private spaces for HIVST kit use and/or
      interpretation. The primary outcome is the proportion of OPD clients tested for
      HIV on the day that they accessed OPD services. Secondary outcome measures are
      the proportion of OPD clients newly identified as HIV-positive and antiretroviral
      therapy (ART) initiation. Costs and cost-effectiveness will be evaluated. Nested
      studies will determine the acceptability of facility-based HIVST among OPD
      clients and health care providers, the presence of adverse events, such as
      coercion to test or unwanted status disclosure, and a process evaluation to
      determine feasibility and scale-up of facility-based HIVST for the future.
      DISCUSSION: This study protocol tests whether facility-based HIVST can positively
      contribute to HIV-testing among OPD clients in resource-limited settings. This
      will be one of the first studies to test the integration of HIVST into facility
      based, primary health services in sub-Saharan Africa. TRIAL REGISTRATION:
      ClinicalTrials.gov, ID: NCT03271307 . Registered on 31 August 2017. Pan African
      Clinical Trials: PACTR201711002697316 . Registered on 1 November 2017.

PMID- 30223876
TI  - Caveat emptor: the combined effects of multiplicity and selective reporting.
AB  - Clinical trials and systematic reviews of clinical trials inform healthcare
      decisions. There is growing concern, however, about results from clinical trials
      that cannot be reproduced. Reasons for nonreproducibility include that outcomes
      are defined in multiple ways, results can be obtained using multiple methods of
      analysis, and trial findings are reported in multiple sources ("multiplicity").
      Multiplicity combined with selective reporting can influence dissemination of
      trial findings and decision-making. In particular, users of evidence might be
      misled by exposure to selected sources and overly optimistic representations of
      intervention effects. In this commentary, drawing from our experience in the
      Multiple Data Sources in Systematic Reviews (MUDS) study and evidence from
      previous research, we offer practical recommendations to enhance the
      reproducibility of clinical trials and systematic reviews.

PMID- 30223875
TI  - Monosodium urate burden assessed with dual-energy computed tomography predicts
      the risk of flares in gout: a 12-month observational study : MSU burden and risk
      of gout flare.
AB  - BACKGROUND: Predicting the risk of flares in patients with gout is a challenge
      and the link between urate burden and the risk of gout flare is unclear. The
      objective of this study was to determine if the extent of monosodium urate (MSU)
      burden measured with dual-energy computed tomography (DECT) and ultrasonography
      (US) is predictive of the risk of gout flares. METHODS: This prospective
      observational study recruited patients with gout to undergo MSU burden assessment
      with DECT (volume of deposits) and US (double contour sign) scans of the knees
      and feet. Patients attended follow-up visits at 3, 6 and 12 months. Patients
      having presented with at least one flare at 6 months were compared to those who
      did not flare. Odds ratios (ORs) (95% confidence interval) for the risk of flare
      were calculated. RESULTS: Overall, 64/78 patients included attended at least one
      follow-up visit. In bivariate analysis, the number of joints with the double
      contour sign was not associated with the risk of flare (p = 0.67). Multivariate
      analysis retained a unique variable: DECT MSU volume of the feet. For each 1 cm3
      increase in DECT MSU volume in foot deposits, the risk of flare increased 2.03
      fold during the first 6 months after initial assessment (OR 2.03 (1.15-4.38)).
      The threshold volume best discriminating patients with and without flare was 0.81
      cm3 (specificity 61%, sensitivity 77%). CONCLUSIONS: This is the first study
      showing that the extent of MSU burden measured with DECT but not US is predictive
      of the risk of flares.

PMID- 30223877
TI  - Early toxicity and patient reported quality-of-life in patients receiving proton
      therapy for localized prostate cancer: a single institutional review of
      prospectively recorded outcomes.
AB  - BACKGROUND: We report prospectively captured clinical toxicity and patient
      reported outcomes in a single institutional cohort of patients treated for
      prostate cancer with proton beam therapy (PBT). This is the largest reported
      series of patients treated mostly with pencil beam scanning PBT. METHODS: We
      reviewed 231 patients treated on an IRB approved institutional registry from 2013
      to 2016; final analysis included 192 patients with > 1-year of follow-up.
      Toxicity incidence was prospectively captured and scored using CTCAE v4.0.
      International Prostate Symptoms Score (IPSS), Sexual Health Inventory for Men
      (SHIM) score, and Expanded Prostate Cancer Index Composite (EPIC) bowel domain
      questionnaires were collected at each visit. Univariate Cox regression was used
      to explore associations of grade 2+ toxicity with clinical, treatment, and
      dosimetric variables. RESULTS: Median follow-up was 1.7 years. Grade 3 toxicity
      was seen in 5/192 patients. No grade 4 or 5 toxicity was seen. Patient reported
      quality-of-life showed no change in urinary function post-radiation by IPSS
      scores. Median SHIM scores declined by 3.7 points at 1-year post-treatment
      without further decrease beyond year 1. On univariate analysis, only younger age
      (HR = 0.61, p = 0.022) was associated with decreased sexual toxicity. EPIC bowel
      domain scores declined from 96 at baseline (median) by an average of 5.4 points
      at 1-year post-treatment (95% CI: 2.5-8.2 points, p < 0.001), with no further
      decrease over time. Bowel toxicity was mostly in the form of transient rectal
      bleeding and was associated with anticoagulation use (HR = 3.45, p = 0.002).
      CONCLUSIONS: Grade 3 or higher toxicity was rare at 2-years after treatment with
      PBT for localized prostate cancer. Longer follow-up is needed to further
      characterize late toxicity and biochemical control. TRIAL REGISTRATION: NCT,
      NCT01255748 . Registered 1 January 2013.

PMID- 30223878
TI  - Longitudinal monitoring of Culicoides in Belgium between 2007 and 2011: local
      variation in population dynamics parameters warrant cautious use of monitoring
      data.
AB  - BACKGROUND: Several European countries suffered important economic losses during
      the past decade due to the emergence of bluetongue and Schmallenberg viruses.
      Both are viruses of veterinary importance and are spread by Culicoides spp. This
      triggered many European countries to start Culicoides population monitoring.
      Recently a one year monitoring study at 16 sites in Belgium revealed that
      important variation existed in Culicoides abundance and species diversity between
      collection sites. In order to analyze whether this variation is consistent over
      years, a detailed analysis of monitoring data collected at seven locations in
      Belgium between 2007 and 2011 was performed in this study. At all locations,
      biting midges were collected with OVI black light traps set-up in close proximity
      to livestock. RESULTS: In total, 42 different Culicoides species were
      morphologically identified. Species of the subgenus Avaritia represented 83% of
      all collected midges. Nevertheless, important differences in species composition
      were found between sites. Furthermore, statistical differences between sites were
      found for the total and maximum annual abundance, showing that a consistent
      higher or lower number of Culicoides could be collected depending on the selected
      collection site. Yearly, up to 16 and 30-fold differences in total and maximum
      annual abundances between sites, respectively, were found. Also the month in
      which most Culicoides were collected varied greatly between years, both at local
      (from May to October) and country level [May (2008), June (2010), July (2009),
      August (2011), October (2007)]. Finally, the average vector-free period over all
      sites and years was 173 days and could roughly be defined between November and
      the end of April. Interestingly, important yearly variations of up to two months
      in the duration of the vector-free period were found between the studied
      collection sites. In contrast to the abundance parameters, no specific sites
      could however be identified where monitoring consistently showed shorter or
      longer vector-free periods. CONCLUSIONS: In conclusion, our results show that the
      selection of collection sites for Culicoides monitoring, even in a small country
      such as Belgium, strongly influences abundance parameters and that yearly
      variation in seasonality occurs. This emphasizes that care should be taken when
      using such parameters in risk assessments for transmission of Culicoides-borne
      diseases and that more clear and strict guidelines for Culicoides monitoring
      should be considered when monitoring data are used for legislative purposes.

PMID- 30223881
TI  - Superiority and non-inferiority: two sides of the same coin?
AB  - BACKGROUND: The classification of phase 3 trials as superiority or non
      inferiority has become routine, and it is widely accepted that there are
      important differences between the two types of trial in their design, analysis
      and interpretation. MAIN TEXT: There is a clear rationale for the superiority/non
      inferiority framework in the context of regulatory trials. The focus of our
      article is non-regulatory trials with a public health objective. First, using two
      examples from infectious disease research, we show that the classification of
      superiority or non-inferiority trials is not always straightforward. Second, we
      show that several arguments for different approaches to the design, analysis and
      interpretation of superiority and non-inferiority trials are unconvincing when
      examined in detail. We consider, in particular, the calculation of sample size
      (and the choice of delta or the non-inferiority margin), intention-to-treat
      versus per-protocol analyses, and one-sided versus two-sided confidence
      intervals. We argue that the superiority/non-inferiority framework is not just
      unnecessary but can have a detrimental effect, being a barrier to clear
      scientific thought and communication. In particular, it places undue emphasis on
      tests for significance or non-inferiority at the expense of estimation. We
      emphasise that these concerns apply to phase 3 non-regulatory trials in general,
      not just to those where the classification of the trial as superiority or non
      inferiority is ambiguous. CONCLUSIONS: Guidelines and statistical practice should
      abandon the sharp division between superiority and non-inferiority phase 3 non
      regulatory trials and be more closely aligned to the clinical and public health
      questions that motivate the trial.

PMID- 30223880
TI  - Low concentrations of monosodium glutamate (MSG) are safe in male Drosophila
      melanogaster.
AB  - OBJECTIVE: Monosodium glutamate (MSG) has been marred by a lot of controversy on
      its safety. In a majority of experimental studies, administration of the compound
      has been parenteral, and yet little is known about MSG safety consumed as a food
      supplement. In this study, we assessed the effects of low concentrations of MSG
      on the activity of hydrogen scavenging, catalase activity and climbing as well as
      lifespan in male Drosophila melanogaster over a 30 days period since this has
      been sparsely studied. RESULTS: No significant differences were associated with
      MSG at 5%, 1%, 0.2%, 0.04% on hydrogen peroxide scavenging, negative geotaxis and
      lifespan in W1118 male D. melanogaster. Significant differences were found in 5%
      MSG on catalase activity, showing that high MSG concentrations would affect
      tissue health in male D. melanogaster. MSG consumed as a food supplement would be
      safe at concentrations below 5% MSG.

PMID- 30223882
TI  - Minimally invasive treatment for anterior pelvic ring injuries with modified
      pedicle screw-rod fixation: a retrospective study.
AB  - BACKGROUND: Pelvic ring injuries constitute only 2 to 8% of all fractures;
      however, they occur in 20% of polytrauma patients. High-energy pelvic fractures
      often result in mechanical instability of the pelvic ring. Successful treatment
      of unstable pelvic ring fractures remains a challenge for orthopedic surgeons.
      This study presents a novel internal fixation method for stabilizing unstable
      anterior pelvic ring fractures using a minimally invasive modified pedicle screw
      rod fixation (MPSRF) technique. METHODS: This retrospective study included six
      patients with unstable pelvic ring injuries who underwent MPSRF, with or without
      posterior fixation. Intraoperative parameters such as blood loss, operative time,
      complications, and quality of reduction (Matta criteria) were recorded and
      evaluated by a blinded reviewer. RESULTS: In the present clinical series, the
      mean operative times and mean blood loss for unilateral versus bilateral anterior
      ring fixations were 176.0 min versus 295.6 min, and 153.3 mL versus 550.0 mL,
      respectively. No iatrogenic neuropraxia of the lateral femoral cutaneous nerve or
      femoral nerve palsy occurred. The reduction quality, graded by the Matta
      criteria, was excellent in five patients and good in one patient. CONCLUSIONS:
      There were no infections, delayed unions, nonunions, or loss of reductions during
      the follow-up period. Only one patient suffered from a broken rod at 4 months
      postoperatively. The modified technique represents a novel, minimally invasive
      procedure for the treatment of anterior pelvic ring fractures and offers a
      reliable and effective alternative to currently available surgical techniques.

PMID- 30223879
TI  - Origin of exon skipping-rich transcriptomes in animals driven by evolution of
      gene architecture.
AB  - BACKGROUND: Alternative splicing, particularly through intron retention and exon
      skipping, is a major layer of pre-translational regulation in eukaryotes. While
      intron retention is believed to be the most prevalent mode across non-animal
      eukaryotes, animals have unusually high rates of exon skipping. However, when and
      how this high prevalence of exon skipping evolved is unknown. Since exon skipping
      can greatly expand proteomes, answering these questions sheds light on the
      evolution of higher organismal complexity in metazoans. RESULTS: We used RNA-seq
      data to quantify exon skipping and intron retention frequencies across 65
      eukaryotic species, with particular focus on early branching animals and
      unicellular holozoans. We found that only bilaterians have significantly
      increased their exon skipping frequencies compared to all other eukaryotic
      groups. Unlike in other eukaryotes, however, exon skipping in nearly all animals,
      including non-bilaterians, is strongly enriched for frame-preserving sequences,
      suggesting that exon skipping involvement in proteome expansion predated the
      increase in frequency. We also identified architectural features consistently
      associated with higher exon skipping rates within all studied eukaryotic genomes.
      Remarkably, these architectures became more prevalent during animal evolution,
      indicating co-evolution between genome architectures and exon skipping
      frequencies. CONCLUSION: We suggest that the increase of exon skipping rates in
      animals followed a two-step process. First, exon skipping in early animals became
      enriched for frame-preserving events. Second, bilaterian ancestors dramatically
      increased their exon skipping frequencies, likely driven by the interplay between
      a shift in their genome architectures towards more exon definition and
      recruitment of frame-preserving exon skipping events to functionally diversify
      their cell-specific proteomes.

PMID- 30223884
TI  - A systematic approach to the recurrent laryngeal nerve dissection at the
      cricothyroid junction.
AB  - BACKGROUND: To describe and evaluate a four step systematic approach to
      dissecting the recurrent laryngeal nerve (RLN) starting at the cricothyroid
      junction during thyroid surgery (subsequently referred to as the retrograde
      medial approach). METHODS: All thyroidectomies completed by the senior author
      between August 2014 and January 2016 were retrospectively reviewed. Patients were
      excluded if concurrent lateral or central neck dissection was performed. A follow
      up period of 1 year was included. RESULTS: Surgical photographs and illustrations
      demonstrate the four steps in the retrograde medial approach to dissection of the
      RLN in thyroid surgery. Three hundred forty-two consecutive thyroid surgeries
      were performed in 17 months, including 213 hemithyroidectomies, 91 total
      thyroidectomies, and 38 completion thyroidectomies. The rate of temporary and
      permanent hypocalcemia was 13% (95% confidence interval [CI]: 8-20%) and 3% (95%
      CI: 1-8%) respectively. The rate of temporary and permanent vocal cord palsy was
      9% (95% CI: 6-12%) and 0.3% (95%CI: 0.01-2%) respectively. The median surgical
      times for hemithyroidectomy, total thyroidectomy, and completion thyroidectomy
      were 39 min (Interquartile range [IQR]: 33-47 min), 48 min (IQR: 40-60 min), and
      40 min (IQR: 35-51 min) respectively. 1% of cases required conversion to an
      alternative surgical approach. CONCLUSION: In a tertiary endocrine head and neck
      practice, the routine use of the retrograde medial approach to RLN dissection is
      safe and results in a short operative time, and a low conversion rate to other
      RLN dissection approaches.

PMID- 30223883
TI  - Novel antibodies against GPIbalpha inhibit pulmonary metastasis by affecting vWF
      GPIbalpha interaction.
AB  - BACKGROUND: Platelet glycoprotein Ibalpha (GPIbalpha) extracellular domain, which
      is part of the receptor complex GPIb-IX-V, plays an important role in tumor
      metastasis. However, the mechanism through which GPIbalpha participates in the
      metastatic process remains unclear. In addition, potential bleeding complication
      remains an obstacle for the clinical use of anti-platelet agents in cancer
      therapy. METHODS: We established a series of screening models and obtained rat
      anti-mouse GPIbalpha monoclonal antibodies (mAb) 1D12 and 2B4 that demonstrated
      potential value in suppressing cancer metastasis. To validate our findings, we
      further obtained mouse anti-human GPIbalpha monoclonal antibody YQ3 through the
      same approach. RESULTS: 1D12 and 2B4 affected the von Willebrand factor (vWF)
      GPIbalpha interaction via binding to GPIbalpha aa 41-50 and aa 277-290
      respectively, which markedly inhibited the interaction among platelets, tumor
      cells, and endothelial cells in vitro, and reduced the mean number of surface
      nodules in the experimental and spontaneous metastasis models in vivo. As
      expected, YQ3 inhibited lung cancer adhesion and demonstrated similar value in
      metastasis. More importantly, for all three mAbs in our study, none of their Fabs
      induced thrombocytopenia. CONCLUSION: Our results therefore supported the
      hypothesis that GPIbalpha contributes to tumor metastasis and suggested potential
      value of using anti-GPIbalpha mAb to suppress cancer metastasis.

PMID- 30223886
TI  - Acquired thrombotic thrombocytopenia purpura associated with severe ADAMTS13
      deficiency in a 3-year-old boy: a case report and review of the literature.
AB  - BACKGROUND: Acquired thrombotic thrombocytopenia purpura is very rarely
      encountered in children. It is often misdiagnosed initially when the condition is
      not inherited. CASE PRESENTATION: We describe a 3-year-old Malay boy who
      presented with simple febrile seizure and had no neurological deficit, however,
      he was found to have microangiopathic hemolytic anemia, thrombocytopenia, and
      elevated serum lactate dehydrogenase. An ADAMTS13 assay results showed zero
      activities (0%), and markedly high level of ADAMTS13 inhibitor (93.15 U/mL)
      confirming the diagnosis of secondary thrombotic thrombocytopenia purpura. He
      received fresh frozen plasma infusions for 3 days and subsequently his platelet
      levels normalized. Serial ADAMTS13 assay results showed improvement. He was also
      given a short course of prednisolone after which the ADAMTS13 activity normalized
      (> 114%) at the end of prednisolone course. CONCLUSIONS: At presentation,
      acquired thrombotic thrombocytopenia purpura in a very young child is commonly
      misdiagnosed as other conditions like idiopathic thrombocytopenic purpura, Evans
      syndrome, atypical hemolytic-uremic syndrome, or malignancy. ADAMTS13 assay
      should be performed early when thrombotic thrombocytopenia purpura is suspected
      as this condition is associated with dire consequences.

PMID- 30223885
TI  - Effect of lycopene on titanium implant osseointegration in ovariectomized rats.
AB  - BACKGROUND: Lycopene prevents bone loss in osteopenic models. However, the role
      of lycopene in the success rate of dental implants under osteopenic conditions
      remains unknown. The aim of this study was to evaluate whether lycopene prevents
      delayed implant osseointegration in an ovariectomized (OVX) rat model. METHODS:
      Thirty female Sprague-Dawley rats were randomly divided into the following
      groups: OVX with vehicle (OVX group), OVX with lycopene (OVX + lycopene group)
      and sham-operated with vehicle (sham group). Twelve weeks after ovariectomy or
      sham operation, titanium implants were placed into the distal metaphysis of the
      bilateral femurs of each rat. These rats were subsequently gavaged with lycopene
      (50 mg/kg/day) or vehicle. After 12 weeks of gavage, all rats were sacrificed,
      and specimens were harvested. Sample osseointegration was evaluated by
      biomechanical testing, 3D micro-computed tomography (micro-CT) analysis and
      histomorphometric analysis. RESULTS: Compared with the OVX group, the OVX +
      lycopene group showed a 69.3% increase in the maximum push-out force (p < 0.01).
      Micro-CT data for the femurs in the OVX + lycopene group showed significantly
      higher bone volume, trabecular thickness and less trabecular space than did those
      in the OVX group. The bone area (BA) around the implant and bone contact (BC)
      with the implant were increased by 72.3% (p < 0.01) and 51.4% (p < 0.01) in the
      OVX + lycopene group, respectively, compared with those in the OVX group. There
      was no significant difference in the mechanical test, micro-CT scanning and
      histomorphometric data between the OVX + lycopene and sham groups (p > 0.05).
      CONCLUSIONS: Lycopene improved implant osseointegration, fixation and bone
      formation under osteopenic conditions, suggesting that lycopene is a promising
      therapeutic agent to prevent delayed implant osseointegration and bone loss under
      osteopenic conditions.

PMID- 30223887
TI  - Carcinoembryonic antigen levels correlated with advanced disease in medullary
      thyroid cancer.
AB  - BACKGROUND: Medullary thyroid cancer (MTC) cells are capable of secreting various
      tumor markers including calcitonin and carcinoembyronic antigen (CEA). The
      purpose of this study is to determine whether abnormal CEA levels may be used as
      a tumor marker to predict the severity of disease in MTC. METHODS: A
      retrospective analysis was completed for 33 patients with MTC who had
      preoperative serum CEA levels. Univariate and multivariate analyses were used to
      quantify the relationship between serum CEA levels and tumor stage and prognosis.
      RESULTS: On multivariate analysis, elevated preoperative CEA levels were
      significantly associated with the size and stage of tumor, distant metastasis,
      decreased biochemical cure, and mortality. There was a significant association
      between tumor size greater than 37 mm and elevated CEA levels (> 271 ng/ml).
      There was also a positive correlation with increased cancer stage (> 377 ng/ml),
      distant metastasis (> 405 ng/ml), and contralateral compartment location of lymph
      node metastasis (> 162 ng/ml). When pre-operative CEA levels are > 500 ng/ml,
      patient mortality was 67%. CONCLUSION: In this study, both pre-operative
      calcitonin and CEA levels were significantly correlated with the extent of
      disease in MTC. While calcitonin has a linear relationship with disease
      progression, abnormal CEA levels were a better indicator of advanced disease. CEA
      levels > 271 ng/ml are significant for advanced tumor size and staging,
      metastasis to the central compartment, and decreased chance of biochemical cure.
      CEA levels greater than 500 ng/ml are associated with significant patient
      mortality.

PMID- 30223888
TI  - Restriction enzyme digestion of host DNA enhances universal detection of
      parasitic pathogens in blood via targeted amplicon deep sequencing.
AB  - BACKGROUND: Targeted amplicon deep sequencing (TADS) of the 16S rRNA gene is
      commonly used to explore and characterize bacterial microbiomes. Meanwhile,
      attempts to apply TADS to the detection and characterization of entire parasitic
      communities have been hampered since conserved regions of many conserved parasite
      genes, such as the 18S rRNA gene, are also conserved in their eukaryotic hosts.
      As a result, targeted amplification of 18S rRNA from clinical samples using
      universal primers frequently results in competitive priming and preferential
      amplification of host DNA. Here, we describe a novel method that employs a single
      pair of universal primers to capture all blood-borne parasites while reducing
      host 18S rRNA template and enhancing the amplification of parasite 18S rRNA for
      TADS. This was achieved using restriction enzymes to digest the 18S rRNA gene at
      cut sites present only in the host sequence prior to PCR amplification. RESULTS:
      This method was validated against 16 species of blood-borne helminths and
      protozoa. Enzyme digestion prior to PCR enrichment and Illumina amplicon deep
      sequencing led to a substantial reduction in human reads and a corresponding 5-
      to 10-fold increase in parasite reads relative to undigested samples. This method
      allowed for discrimination of all common parasitic agents found in human blood,
      even in cases of multi-parasite infection, and markedly reduced the limit of
      detection in digested versus undigested samples. CONCLUSIONS: The results herein
      provide a novel methodology for the reduction of host DNA prior to TADS and
      establish the validity of a next-generation sequencing-based platform for
      universal parasite detection.

PMID- 30223890
TI  - The Riemerella anatipestifer M949_RS01035 gene is involved in bacterial
      lipopolysaccharide biosynthesis.
AB  - In this study, the Riemerella anatipestifer mutant strain RA1062 was obtained by
      screening a random Tn4351 transposon mutant library. The mutant strain was
      unreactive with the anti-CH3 lipopolysaccharide monoclonal antibody, as
      demonstrated with an enzyme-linked immunosorbent assay, and its M949_RS01035 gene
      was inactivated. When cultured in trypticase soy broth, the late stage growth of
      the mutant RA1062 was significantly decreased. The mutant RA1062 was stained with
      crystal violet and presented a rough lipopolysaccharide phenotype, which differed
      from that of the wild-type strain CH3, suggesting that deletion of the
      M949_RS01035 gene resulted in defective lipopolysaccharide. Silver staining and
      Western blot analyses further confirmed that the RA1062 lipopolysaccharide had a
      deficiency in ladder-like binding pattern, as compared to lipopolysaccharide of
      the wild-type CH3 strain. In addition, the mutant RA1062 showed a higher
      susceptibility to complement-dependent killing, increased bacterial adhesion and
      invasion capacities to Vero cells, decreased blood bacterial loads, and
      attenuated virulence in infected ducks, when compared to the wild-type strain
      CH3. Moreover, RNA-Seq and real-time polymerase chain reaction analyses indicated
      that two genes were up-regulated and two were down-regulated in the mutant RA1062
      genome. Furthermore, an animal protection experiment showed that immunization of
      ducks with inactivated RA1062 bacterin conferred effective cross-protection
      against challenge with the virulent R. anatipestifer serotypes 1, 2, and 10. This
      study presents evidence that the M949_RS01035 gene is involved in bacterial
      phenotype, virulence, and gene regulation in R. anatipestifer. The mutant strain
      RA1062 could be used as a cross-protective vaccine candidate.

PMID- 30223891
TI  - Cardiovascular and microvascular outcomes of glucagon-like peptide-1 receptor
      agonists in type 2 diabetes: a meta-analysis of randomized controlled
      cardiovascular outcome trials with trial sequential analysis.
AB  - BACKGROUND: Efficacy trials showed that glucagon-like peptide-1 receptor (GLP1R)
      agonists reduced metabolic risk factors in addition to glucose lowering, but the
      cardiovascular and microvascular efficacy of this drug class remains to be
      determined. We aimed to evaluate the overall cardiovascular and microvascular
      efficacy of GLP1R agonists by performing a meta-analysis with trial sequential
      analysis. METHODS: Randomized controlled, cardiovascular outcomes trials
      including at least 2000 patient-years' follow-up and 100 composite cardiovascular
      events were included. Trial sequential analysis (TSA) was performed and the
      quality of evidence was graded. RESULTS: Thirty-three thousand four hundred fifty
      seven patients and 4105 cardiovascular events from 4 large trials were included.
      GLP1R agonists were associated with a statistically significant reduction in
      risks for all-cause mortality (hazard ratio [HR]: 0.88, 95% CI: 0.81 to 0.95;
      number needed to treat [NNT]: 286 person-years), cardiovascular mortality (HR:
      0.87, 95% CI: 0.79 to 0.96; NNT: 412 person-years), stroke (HR: 0.87, 95% CI:
      0.76 to 0.98; NNT: 209 person-years) and the composite adverse cardiovascular
      outcome (MACE; HR: 0.91, 95% CI: 0.85 to 0.96; NNT: 241 person-years). The
      magnitude of benefit on MACE was attenuated in patients with a history of
      congestive heart failure (HR: 0.96, 95% CI: 0.85 to 1.08 with; HR: 0.87, 95% CI:
      0.77 to 1.00 without). The risks for hospitalization for heart failure and
      myocardial infarction were not significantly different. The quality of the
      evidence was deemed as moderate to high based on GRADE approach. TSA provided
      firm evidence for a 10% reduction in all-cause mortality, a 15% reduction in
      MACE, and lack of a 15% reduction in hospitalization for heart failure, but
      evidence remains inconclusive for cardiovascular mortality and myocardial
      infarction. GLP1R agonists numerically reduced the rates for nephropathy but the
      risk for retinopathy was similar. CONCLUSIONS: Meta-analysis with trial
      sequential analysis suggested that GLP1R agonists significantly reduced the risk
      for all-cause mortality and composite cardiovascular outcomes, but the reduction
      of cardiovascular mortality remains to be confirmed.

PMID- 30223889
TI  - Single-cell genomics of co-sorted Nanoarchaeota suggests novel putative host
      associations and diversification of proteins involved in symbiosis.
AB  - BACKGROUND: Nanoarchaeota are obligate symbionts of other Archaea first
      discovered 16 years ago, yet little is known about this largely uncultivated
      taxon. While Nanoarchaeota diversity has been detected in a variety of habitats
      using 16S rRNA gene surveys, genome sequences have been available for only three
      Nanoarchaeota and their hosts. The host range and adaptation of Nanoarchaeota to
      a wide range of environmental conditions has thus largely remained elusive.
      Single-cell genomics is an ideal approach to address these questions as
      Nanoarchaeota can be isolated while still attached to putative hosts, enabling
      the exploration of cell-cell interactions and fine-scale genomic diversity.
      RESULTS: From 22 single amplified genomes (SAGs) from three hot springs in
      Yellowstone National Park, we derived a genome-based phylogeny of the phylum
      Nanoarchaeota, linking it to global 16S rRNA gene diversity. By exploiting
      sequencing of co-sorted tightly attached cells, we associated Nanoarchaeota with
      6 novel putative hosts, 2 of which were found in multiple SAGs, and showed that
      the same host species may associate with multiple species of Nanoarchaeota.
      Comparison of single nucleotide polymorphisms (SNPs) within a population of
      Nanoarchaeota SAGs indicated that Nanoarchaeota attached to a single host cell in
      situ are likely clonal. In addition to an overall pattern of purifying selection,
      we found significantly higher densities of non-synonymous SNPs in hypothetical
      cell surface proteins, as compared to other functional categories. Genes
      implicated in interactions in other obligate microbe-microbe symbioses, including
      those encoding a cytochrome bd-I ubiquinol oxidase and a FlaJ/TadC homologue
      possibly involved in type IV pili production, also had relatively high densities
      of non-synonymous SNPs. CONCLUSIONS: This population genetics study of
      Nanoarchaeota greatly expands the known potential host range of the phylum and
      hints at what genes may be involved in adaptation to diverse environments or
      different hosts. We provide the first evidence that Nanoarchaeota cells attached
      to the same host cell are clonal and propose a hypothesis for how clonality may
      occur despite diverse symbiont populations.

PMID- 30223893
TI  - Coming to terms with oneself: a mixed methods approach to perceived self-esteem
      of adult survivors of childhood maltreatment in foster care settings.
AB  - BACKGROUND: A broad range of psychopathological sequelae was found in adult
      survivors of institutional childhood maltreatment (IM). Childhood maltreatment is
      also associated with lower self-esteem (SE). In previous qualitative research,
      adult survivors of IM reported feelings of worthlessness and self-doubts, but
      research on IM and its associations with SE is still scarce. METHOD: To
      investigate the emotional facet of SE in 46 adult survivors of IM in foster care
      settings provided by the City of Vienna we used the Emotional SE subscale of the
      Multidimensional Self-Esteem Scale ('Multidimensionale Selbstwertskala', MSWS)
      and applied a semi-structured interview with open-ended questions. Qualitative
      data were analyzed with thematic analysis. Finally, qualitative and quantitative
      data were merged in a mixed method approach to detect similarities and
      differences between both assessment modalities. RESULTS: Findings showed a
      significantly lower emotional SE level (MSWS) in adult survivors compared to a
      norm sample. Qualitative findings revealed five main themes reporting positive
      and negative emotions and attitudes towards oneself. Merged data showed a
      tendency of more positive attitudes and emotions within participants with higher
      emotional SE levels and more negative attitudes within participants with lower
      levels. No gender differences were found in both data sets. CONCLUSIONS: IM seems
      to predict lower emotional SE. Observed qualitative aspects of emotional SE seem
      to concur with symptoms of disturbances in self-organization (DSO) that are
      typically present in persons suffering from Complex PTSD. Considering emotional
      SE in future research could facilitate the understanding of the sequelae of
      complex trauma.

PMID- 30223892
TI  - Prokaryotic horizontal gene transfer within the human holobiont: ecological
      evolutionary inferences, implications and possibilities.
AB  - The ubiquity of horizontal gene transfer in the living world, especially among
      prokaryotes, raises interesting and important scientific questions regarding its
      effects on the human holobiont i.e., the human and its resident bacterial
      communities considered together as a unit of selection. Specifically, it would be
      interesting to determine how particular gene transfer events have influenced
      holobiont phenotypes in particular ecological niches and, conversely, how
      specific holobiont phenotypes have influenced gene transfer events. In this
      synthetic review, we list some notable and recent discoveries of horizontal gene
      transfer among the prokaryotic component of the human microbiota, and analyze
      their potential impact on the holobiont from an ecological-evolutionary
      viewpoint. Finally, the human-Helicobacter pylori association is presented as an
      illustration of these considerations, followed by a delineation of unresolved
      questions and avenues for future research.

PMID- 30223894
TI  - Mesenchymal stem cells alleviate experimental autoimmune cholangitis through
      immunosuppression and cytoprotective function mediated by galectin-9.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) play an anti-inflammatory role by
      secreting certain bioactive molecules to exert their therapeutic effects for
      disease treatment. However, the underlying mechanism of MSCs in chronic
      autoimmune liver diseases-primary biliary cholangitis (PBC), for example-remains
      to be elucidated. METHODS: Human umbilical cord-derived MSCs (UC-MSCs) were
      injected intravenously into 2-octynoic acid coupled to bovine serum albumin (2OA
      BSA)-induced autoimmune cholangitis mice. Serum levels of biomarkers and
      autoantibodies, histologic changes in the liver, diverse CD4+ T-cell subsets in
      different tissues, and chemokine activities were analyzed. Moreover, we
      investigated galectin-9 (Gal-9) expression and its function in UC-MSCs. RESULTS:
      In this study, UC-MSC transplantation (UC-MSCT) significantly ameliorated liver
      inflammation, primarily by diminishing T helper 1 (Th1) and Th17 responses as
      well as modifying liver chemokine activities in experimental autoimmune
      cholangitis mice. Mechanistically, UC-MSCs significantly repressed the
      proliferation of CD4+ T cells and suppressed the differentiation of Th1 and Th17
      cells, which was likely dependent on Gal-9. Furthermore, the signal transducer
      and activator of transcription (STAT) and c-Jun N-terminal kinase (JNK) signaling
      pathways were involved in the production of Gal-9 in UC-MSCs. CONCLUSIONS: These
      results suggest that Gal-9 contributes significantly to UC-MSC-mediated
      therapeutic effects and improve our understanding of the immunomodulatory
      mechanisms of MSCs in the treatment of PBC.

PMID- 30223896
TI  - Improving vaccination uptake in pediatric Cochlear implant recipients.
AB  - BACKGROUND: An Infectious Disease vaccine specialist joined our institution's
      Cochlear Implant Team in 2010 in order to address the high percentage of non
      compliance to immunization prior to surgery identified previously from an
      internal review. The purpose of this study was to (1) review the immunization
      status of cochlear implant recipients in 2010-2014, (2) assess if introducing a
      vaccine specialist made a significant change in vaccination compliance and (3)
      elucidate any barriers to vaccination compliance. METHODS: Retrospective chart
      review and a telephone survey. Medical records of 116 cochlear implant recipients
      between 2010 and 2014 were reviewed. A telephone survey was conducted to obtain
      the current vaccination status in children who required post-operative
      vaccinations with incomplete records on chart review and, if applicable, the
      reason for non-compliance. RESULTS: Between 2010 and 2014, 98% of children were
      up-to-date at the time of surgery, compared to 67% up-to-date at the time of
      surgery between 2002 and 2007. 27 children were included in our post-operative
      immunization analysis. 29.6% (8/27) failed to receive necessary vaccinations post
      surgery. Pneumovax-23, a vaccine for high-risk patients (such as cochlear implant
      candidates) was missed in all cases. CONCLUSION: Pre-operative vaccination for
      cochlear implant recipients improved dramatically with the addition of a vaccine
      specialist. However, a significant proportion of patients requiring vaccinations
      post-surgery did not receive them. The main reason for non-compliance was due to
      parents being unaware that their children required this vaccine postoperatively
      by being "high-risk". Although improvement was demonstrated, a communication gap
      continued to impede the adequacy of vaccination uptake in pediatric cochlear
      implant recipients following surgery at age 2 when the high-risk vaccine was due.

PMID- 30223895
TI  - Protocol for a systematic review to identify the barriers and facilitators to
      deliver bystander cardiopulmonary resuscitation (CPR) in disadvantaged
      communities.
AB  - BACKGROUND: A key determinant of survival after out-of-hospital cardiac arrest
      (OHCA) is bystander cardio pulmonary resuscitation (CPR) which can more than
      double an individual's chances of surviving to discharge from hospital. The
      experience of other international OHCA survival programmes has shown that
      increasing bystander CPR is strongly associated with an increase in overall
      survival. However, existing data suggest that the more economically deprived an
      area is the higher the incidence of cardiac arrest. At the same time, rates of
      bystander CPR in the same areas are lower, which could result in lower survival
      rates. High-profile awareness raising campaigns that are generic focus have not
      specifically targeted people living in deprived communities who may require more
      tailored campaigns and interventions to change attitudes and improve confidence
      to administer bystander CPR. Therefore, this systematic review will explore the
      facilitators and barriers to engaging with bystander CPR which exist in deprived
      communities The secondary objective is to identify existing bystander OHCA social
      marketing and social network intervention campaigns that could inform future
      activities to improve the rate of bystander CPR in deprived communities. METHODS:
      Systematic review searching the following databases: CINAHL, MEDLINE, PsycINFO,
      and Web of Science Core Collection Citation Indexes. Unpublished 'grey'
      literature will also be sourced through web searches, stakeholder interviews, and
      an advisory group. The reference lists of any relevant reviews will also be
      checked for additional studies. References will be restricted to those published
      in 2000 onwards. Authors will independently screen, assess data quality, and
      extract data for synthesis. A narrative synthesis of study findings will be
      conducted, with findings presented thematically. DISCUSSION: This review will
      focus on all studies that seek to examine the barriers and facilitators to the
      delivery of bystander CPR in deprived communities and identify examples of
      previous interventions or activities that could inform the design of a future
      theory-based intervention to improve the rate of bystander CPR in deprived
      communities. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017081944.

PMID- 30223897
TI  - Ontoserver: a syndicated terminology server.
AB  - BACKGROUND: Even though several high-quality clinical terminologies, such as
      SNOMED CT and LOINC, are readily available, uptake in clinical systems has been
      slow and many continue to capture information in plain text or using custom
      terminologies. This paper discusses some of the challenges behind this slow
      uptake and describes a clinical terminology server implementation that aims to
      overcome these obstacles and contribute to the widespread adoption of
      standardised clinical terminologies. RESULTS: Ontoserver is a clinical
      terminology server based on the Fast Health Interoperability Resources (FHIR)
      standard. Some of its key features include: out-of-the-box support for SNOMED CT,
      LOINC and OWL ontologies, such as the Human Phenotype Ontology (HPO); a fast,
      prefix-based search algorithm to ensure users can easily find content and are not
      discouraged from entering coded data; a syndication mechanism to facilitate
      keeping terminologies up to date; and a full implementation of SNOMED CT's
      Expression Constraint Language (ECL), which enables sophisticated data analytics.
      CONCLUSIONS: Ontoserver has been designed to overcome some of the challenges that
      have hindered adoption of standardised clinical terminologies and is used in
      several organisations throughout Australia. Increasing adoption is an important
      goal because it will help improve the quality of clinical data, which can lead to
      better clinical decision support and ultimately to better patient outcomes.

PMID- 30223898
TI  - Porcine sapovirus Cowden strain enters LLC-PK cells via clathrin- and cholesterol
      dependent endocytosis with the requirement of dynamin II.
AB  - Caliciviruses in the genus Sapovirus are a significant cause of viral
      gastroenteritis in humans and animals. However, the mechanism of their entry into
      cells is not well characterized. Here, we determined the entry mechanism of
      porcine sapovirus (PSaV) strain Cowden into permissive LLC-PK cells. The
      inhibition of clathrin-mediated endocytosis using chlorpromazine, siRNAs, and a
      dominant negative (DN) mutant blocked entry and infection of PSaV Cowden strain,
      confirming a role for clathrin-mediated internalization. Entry and infection were
      also inhibited by the cholesterol-sequestering drug methyl-beta-cyclodextrin and
      was restored by the addition of soluble cholesterol, indicating that cholesterol
      also contributes to entry and infection of this strain. Furthermore, the
      inhibition of dynamin GTPase activity by dynasore, siRNA depletion of dynamin II,
      or overexpression of a DN mutant of dynamin II reduced the entry and infection,
      suggesting that dynamin mediates the fission and detachment of clathrin- and
      cholesterol-pits for entry of this strain. In contrast, the inhibition of
      caveolae-mediated endocytosis using nystatin, siRNAs, or a DN mutant had no
      inhibitory effect on entry and infection of this strain. It was further
      determined that cell entry of PSaV Cowden strain required actin rearrangements
      for vesicle internalization, endosomal trafficking from early to late endosomes
      through microtubules, and late endosomal acidification for uncoating. We conclude
      that PSaV strain Cowden is internalized into LLC-PK cells by clathrin- and
      cholesterol-mediated endocytosis that requires dynamin II and actin
      rearrangement, and that the uncoating occurs in the acidified late endosomes
      after trafficking from the early endosomes through microtubules.

PMID- 30223900
TI  - Identification of TBX2 and TBX3 variants in patients with conotruncal heart
      defects by target sequencing.
AB  - BACKGROUND: Conotruncal heart defects (CTDs) are heterogeneous congenital heart
      malformations that result from outflow tract dysplasia; however, the genetic
      determinants underlying CTDs remain unclear. Increasing evidence demonstrates
      that dysfunctional TBX2 and TBX3 result in outflow tract malformations, implying
      that both of them are involved in CTD pathogenesis. We screened for TBX2 and TBX3
      variants in a large cohort of CTD patients (n = 588) and population-matched
      healthy controls (n = 300) by target sequencing and genetically analyzed the
      expression and function of these variants. RESULTS: The probably damaging
      variants p.R608W, p.T249I, and p.R616Q of TBX2 and p.A192T, p.M65L, and p.A562V
      of TBX3 were identified in CTD patients, but none in controls. All altered amino
      acids were highly conserved evolutionarily. Moreover, our data suggested that
      mRNA and protein expressions of TBX2 and TBX3 variants were altered compared with
      those of the wild-type. We screened PEA3 and MEF2C as novel downstream genes of
      TBX2 and TBX3, respectively. Functional analysis revealed that TBX2R608W and
      TBX2R616Q variant proteins further activated HAS2 promoter but failed to activate
      PEA3 promoter and that TBX3A192T and TBX3A562V variant proteins showed a reduced
      transcriptional activity over MEF2C promoter. CONCLUSIONS: Our results indicate
      that the R608W and R616Q variants of TBX2 as well as the A192T and A562V variants
      of TBX3 contribute to CTD etiology; this was the first association of variants of
      TBX2 and TBX3 to CTDs based on a large population.

PMID- 30223899
TI  - Sex differences in ischemic heart disease and heart failure biomarkers.
AB  - Since 1984, each year, more women than men die of ischemic heart disease (IHD)
      and heart failure (HF), yet more men are diagnosed. Because biomarker assessment
      is often the first diagnostic employed in such patients, understanding biomarker
      differences in men vs. women may improve female morbidity and mortality
      rates.Some key examples of cardiac biomarker utility based on sex include
      contemporary use of "unisex" troponin reference intervals under-diagnosing
      myocardial necrosis in women; greater use of hsCRP in the setting of acute
      coronary syndrome (ACS) could lead to better stratification in women; and greater
      use of BNP with sex-specific thresholds in ACS could also lead to more timely
      risk stratification in women.Accurate diagnosis, appropriate risk management, and
      monitoring are key in the prevention and treatment of cardiovascular diseases;
      however, the assessment tools used must also be useful or at least assessed for
      utility in both sexes. In other words, going forward, we need to evaluate sex
      specific reference intervals or cutoffs for laboratory tests used to assess
      cardiovascular disease to help close the diagnostic gap between men and women.

PMID- 30223901
TI  - Validation and comparison of the Arabic versions of GOHAI and OHIP-14 in patients
      with and without denture experience.
AB  - BACKGROUND: The assessment of oral heath related quality of life (OHRQoL) for
      complete denture wearers according to a participant's subjective perception may
      provide an indication of the adaptive capacity of the individual. The aim of this
      study was to compare and assess the validation of two quality of life measures,
      the Oral Health Impact Profile-14 (OHIP-14) and Geriatric Oral Health Assessment
      Index (GOHAI), in patients with and without previous denture experience. METHODS:
      A total of 69 elders (36 male and 34 female; mean age, 63 years) from Dental
      Clinics of the University of Khartoum and the National University in Sudan, with
      and without previous denture experience, were included in the study. OHRQoL was
      assessed using two Arabic-translated questionnaires (OHIP-14 and GOHAI) before
      and after complete denture therapy. Global self-ratings of oral and general
      health were obtained, and denture satisfaction was assessed using the Denture
      Satisfaction questionnaire. RESULTS: Both tools had significant correlations with
      self-rating oral health in patients without denture experience (P < 0.05).
      However, no significant correlations were found in patients with denture
      experience. There were significant differences between pre-and post-treatment
      total scores with both the GOHAI and OHIP-14 (P < 0.001). Responsiveness to
      treatment using GOHAI and OHIP-14 revealed overall mean effect size higher in
      patients without (1.49) and (0.83) than those with previous denture experience
      (0.89) and (0.60), respectively. However, neither tool could detect significant
      differences between patients with and without denture experience (P > 0.05).
      CONCLUSION: Greater improvements of OHRQoL after complete denture therapy were
      observed in participants without than those with previous denture experience. The
      Arabic-translated versions of GOHAI and OHIP-14 can be regarded as effective
      measures for assessing treatment outcomes of complete denture therapy.

PMID- 30223902
TI  - Dehydroepiandrosterone (DHEA) supplementation improves in vitro fertilization
      outcomes of poor ovarian responders, especially in women with low serum
      concentration of DHEA-S: a retrospective cohort study.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) is now widely used as an adjuvant for
      in vitro fertilization (IVF) cycles in poor ovarian responders (PORs). Several
      studies showed that DHEA supplementation could improve IVF outcomes of PORs.
      However, most of the PORs do not respond to DHEA clinically. Therefore, the aim
      of this study is to confirm the beneficial effects of DHEA on IVF outcomes of
      PORs and to investigate which subgroups of PORs can best benefit from DHEA
      supplementation. METHODS: This retrospective cohort study was performed between
      January 2015 and December 2017. A total of 151 PORs who fulfilled the Bologna
      criteria and underwent IVF cycles with the gonadotropin-releasing hormone
      antagonist protocol were identified. The study group (n = 67) received 90 mg of
      DHEA daily for an average of 3 months before the IVF cycles. The control group (n
      = 84) underwent the IVF cycles without DHEA pretreatment. The basic and cycle
      characteristics and IVF outcomes between the two groups were compared using
      independent t-tests, Chi-Square tests and binary logistic regression. RESULTS:
      The study and control groups did not show significant differences in terms of
      basic characteristics. The study group demonstrated a significantly greater
      number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3
      embryos and top-quality embryos at day 3 and a higher clinical pregnancy rate,
      ongoing pregnancy rate and live birth rate than those measures in the control
      group. The multivariate analysis revealed that DHEA supplementation was
      positively associated with clinical pregnancy rate (OR = 4.93, 95% CI 1.68-14.43,
      p = 0.004). Additionally, in the study group, the multivariate analysis showed
      that serum dehydroepiandrosterone-sulfate (DHEA-S) levels < 180 MUg/dl were
      significantly associated with a rate of retrieved oocytes > 3 (OR = 5.92, 95% CI
      1.48-23.26, p = 0.012). CONCLUSIONS: DHEA supplementation improves IVF outcomes
      of PORs. In PORs with DHEA pretreatment, women with lower DHEA-S level may have
      greater possibility of attaining more than 3 oocytes.

PMID- 30223903
TI  - Optimising pain management in children with acute otitis media through a primary
      care-based multifaceted educational intervention: study protocol for a cluster
      randomised controlled trial.
AB  - BACKGROUND: Whilst current guidelines highlight the importance of pain management
      for children with acute otitis media (AOM), there is evidence to suggest that
      this is not implemented in everyday practice. We have developed a primary care
      based multifaceted educational intervention to optimise pain management in
      children with AOM, and we trial its clinical and cost effectiveness. METHODS:
      This cluster randomised controlled trial aims to recruit 250 children aged 6
      months to 10 years presenting with AOM to general practitioners (GPs) in 30
      primary care centres (PCCs) across the Netherlands. GPs in the PCCs allocated to
      the intervention group receive a blended GP educational programme (online and
      face-to-face training). The intervention asks GPs to proactively discuss pain
      management with parents using an information leaflet, and to prescribe
      paracetamol and ibuprofen according to current guidelines. GPs in both groups
      complete an online module illustrating various otoscopic images to standardise
      AOM diagnosis. GPs in the PCCs allocated to the control group do not receive any
      further training and provide 'care as usual'. During the 4-week follow-up,
      parents complete a symptom diary. The primary outcome is the difference in parent
      reported mean earache scores over the first 3 days. Secondary outcomes include
      both number of days with earache and fever, GP re-consultations for AOM,
      antibiotic prescriptions, and costs. Analysis will be by intention-to-treat.
      DISCUSSION: The optimal use of analgesics through the multifaceted intervention
      may provide symptom relief and thereby reduce re-consultations and antibiotic
      prescriptions in children with AOM. TRIAL REGISTRATION: Netherlands Trial
      Register, NTR4920 . Registered on 19 December 2014.

PMID- 30223904
TI  - Steroid insensitive fixed airflow obstruction is not related to airway
      inflammation in older non-smokers with asthma.
AB  - There is limited evidence linking airway inflammation and lung function
      impairment in older non-smoking asthmatics with fixed airflow obstruction (FAO),
      which can develop despite treatment with inhaled corticosteroids (ICS). We
      assessed lung function (spirometry, forced oscillation technique (FOT)), lung
      elastic recoil and airway inflammation using bronchoalveolar lavage (BAL) in non
      smoking adult asthmatics with FAO, following 2 months treatment with high-dose
      ICS/long-acting beta-agonist. Subjects demonstrated moderate FAO, abnormal FOT
      indices and loss of lung elastic recoil. This cross-sectional study showed a lack
      of a relationship between BAL neutrophils, eosinophils, inflammatory cytokines
      and lung function impairment. Other inflammatory pathways or the effect of
      inflammation on lung function over time may explain FAO development.

PMID- 30223905
TI  - Development of the Finnish neurological function testing battery for dogs and its
      intra- and inter-rater reliability.
AB  - BACKGROUND: The Finnish neurological function testing battery for dogs (FINFUN)
      was developed to meet the increasing demand for objective outcome measures in
      veterinary physiotherapy. The testing battery should provide consistent,
      reproducible results and have established face and content validity. Internal
      consistency and intra- and inter-rater reliability of the FINFUN were also
      investigated. RESULTS: The FINFUN comprised 11 tasks: lying, standing up from
      lying, sitting, standing up from sitting, standing, proprioceptive positioning,
      starting to walk, walking, trotting, walking turns and walking stairs. A score
      from 0 to 4, (0: unable to perform task, 4: performing task with normal motor
      function) was given for each task, the maximum score being 44. Twenty-six dogs
      were filmed when performing the FINFUN. Seven observers scored the performances
      from the video recordings. The FINFUN was considered to have appropriate face and
      content validity based on a pilot study, clinical experience and critical
      reflection of the development process. Its internal consistency was excellent,
      with no Cronbach's alpha values below 0.922. The intra-rater reliability for
      total score of experienced observers was almost perfect: 0.999 (observer 1) and
      0.994 (observer 2). The inter-rater reliability for both experienced and novice
      observers' total scores was also almost perfect (0.919-0.993). Analysis of each
      individual task showed substantial intra-rater and inter-rater agreement for the
      tasks "lying" and "sitting". CONCLUSIONS: The FINFUN is an objective, valid and
      reliable tool with standardized scoring criteria for evaluation of motor function
      in dogs recovering from spinal cord injury.

PMID- 30223907
TI  - The association between gestational age and otitis media during childhood: a
      population-based cohort analysis.
AB  - Otitis media (OM) carries a tremendous global health burden and potentially
      severe long-term consequences. The objective of this study was to determine the
      impact of birth at different gestational ages on the incidence of childhood OM.A
      population-based cohort analysis was conducted. All singleton deliveries
      occurring between 1991 and 2014 at a regional tertiary medical center were
      included. Gestational age on delivery was divided into six subgroups: early (<34
      weeks gestation; 0 out of 7) and late (34 weeks gestation; 0 out of 7 to 36 weeks
      gestation; 6 out of 7) preterm, and early (37 weeks gestation; 0 out of 7 to 38
      weeks gestation; 6 out of 7), full (39 weeks gestation; 0 out of 7 to 40 weeks
      gestation; 6 out of 7), late (41 weeks gestation; 0 out of 7 to 41 weeks
      gestation; 6 out of 7) and post (?42 weeks 0 out of 7) term deliveries. Rates of
      OM-related hospitalizations up to 18 years of age were assessed. Weibull
      parametric hazards model was used to study the association between gestational
      age at birth and the risk for OM-related hospitalizations while controlling for
      potential confounders.During the study period, 238,622 deliveries met the
      inclusion criteria. OM-related hospitalizations of the offspring (n=4724) were
      significantly more common in the preterm (early 3.6%, late 2.4%) and early-term
      born children (2.2%) and decreased gradually across the full (1.9%), late (1.7%)
      and post (1.6%) term groups (chi2-test for trends P<0.001). In the Weibull
      regression model, early preterm, as well as early-term deliveries exhibited an
      independent association with pediatric OM (adjusted hazard ratios: 1.67 and 1.09,
      respectively, P<0.02).Deliveries occurring at preterm and early term are
      associated with higher rates of pediatric OM-related hospitalizations, which
      decrease gradually as gestational age advances.

PMID- 30223908
TI  - Embryonic development of teleost Brycon orbignyanus.
AB  - Brycon orbignyanus is an important large teleost that is currently on the list of
      endangered species, therefore studies on its reproductive biology and embryology
      are fundamental to help species conservation and recovery. The objective of this
      research was to characterize the events that occur during extrusion,
      fertilization and embryonic development of the species. The samples were
      collected at predetermined times, fixed and processed for light microscopy and
      scanning electron microscopy. The greenish oocytes were spherical, had
      translucent chorion and a mean diameter of 1.3+/-0.11 mm. The eggs had well
      defined animal and vegetative poles approximately 18 min post-fertilization.
      Stages from 2 to 128 blastomeres occurred between 20 min and 3 h post
      fertilization (hPF), when the morula was characterized. The blastula stage was
      observed between 2 and 3 hPF, and the gastrula between 3 and 7 hPF, when the
      embryonic shield emerged and the cellular migration with the consequent formation
      of epiblast and hypoblast. At 8 hPF, the formation of the neural tube, above the
      notochord and the encephalic region, was observed, delimiting the forebrain,
      mesencephalon and rhombencephalon regions. From 11 hPF onward, the optic vesicle
      was formed close to the forebrain and the embryo tail was well developed. The
      optic vesicle was observed from 12 hPF onward, and the tail showed an intense
      movement that culminated with the rupture of the chorion and consequent hatching
      of the larva at 13 hPF and 27 degrees C.

PMID- 30223906
TI  - Lignocellulose degradation at the holobiont level: teamwork in a keystone soil
      invertebrate.
AB  - BACKGROUND: Woodlice are recognized as keystone species in terrestrial ecosystems
      due to their role in the decomposition of organic matter. Thus, they contribute
      to lignocellulose degradation and nutrient cycling in the environment together
      with other macroarthropods. Lignocellulose is the main component of plants and is
      composed of cellulose, lignin and hemicellulose. Its digestion requires the
      action of multiple Carbohydrate-Active enZymes (called CAZymes), typically acting
      together as a cocktail with complementary, synergistic activities and modes of
      action. Some invertebrates express a few endogenous lignocellulose-degrading
      enzymes but in most species, an efficient degradation and digestion of
      lignocellulose can only be achieved through mutualistic associations with
      endosymbionts. Similar to termites, it has been suspected that several bacterial
      symbionts may be involved in lignocellulose degradation in terrestrial isopods,
      by completing the CAZyme repertoire of their hosts. RESULTS: To test this
      hypothesis, host transcriptomic and microbiome shotgun metagenomic datasets were
      obtained and investigated from the pill bug Armadillidium vulgare. Many genes of
      bacterial and archaeal origin coding for CAZymes were identified in the
      metagenomes of several host tissues and the gut content of specimens from both
      laboratory lineages and a natural population of A. vulgare. Some of them may be
      involved in the degradation of cellulose, hemicellulose, and lignin.
      Reconstructing a lignocellulose-degrading microbial community based on the
      prokaryotic taxa contributing relevant CAZymes revealed two taxonomically
      distinct but functionally redundant microbial communities depending on host
      origin. In parallel, endogenous CAZymes were identified from the transcriptome of
      the host and their expression in digestive tissues was demonstrated by RT-qPCR,
      demonstrating a complementary enzyme repertoire for lignocellulose degradation
      from both the host and the microbiome in A. vulgare. CONCLUSIONS: Our results
      provide new insights into the role of the microbiome in the evolution of
      terrestrial isopods and their adaptive radiation in terrestrial habitats.

PMID- 30223909
TI  - Prefrontal glutamate levels predict altered amygdala-prefrontal connectivity in
      traumatized youths.
AB  - BACKGROUND: Neurobiological models of stress and stress-related mental illness,
      including post-traumatic stress disorder, converge on the amygdala and the
      prefrontal cortex (PFC). While a surge of research has reported altered
      structural and functional connectivity between amygdala and the medial PFC
      following severe stress, few have addressed the underlying neurochemistry.
      METHODS: We combined resting-state functional magnetic resonance imaging measures
      of amygdala connectivity with in vivo MR-spectroscopy (1H-MRS) measurements of
      glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control
      subjects. RESULTS: Traumatized youths showed altered amygdala-anterior
      midcingulate cortex (aMCC) and amygdala-ventromedial prefrontal cortex (vmPFC)
      connectivity. Moreover, the trauma survivors exhibited reduced levels of
      glutamate in the vmPFC which fits with the previous findings of reduced levels of
      Glx (glutamate + glutamine) in the aMCC (Ousdal et al., 2017) and together
      suggest long-term impact of a traumatic experience on glutamatergic pathways.
      Importantly, local glutamatergic metabolite levels predicted the individual
      amygdala-aMCC and amygdala-vmPFC functional connectivity, and also mediated the
      observed group difference in amygdala-aMCC connectivity. CONCLUSIONS: Our
      findings suggest that traumatic stress may influence amygdala-prefrontal neuronal
      connectivity through an effect on prefrontal glutamate and its compounds.
      Understanding the neurochemical underpinning of altered amygdala connectivity
      after trauma may ultimately lead to the discovery of new pharmacological agents
      which can prevent or treat stress-related mental illness.

PMID- 30223910
TI  - Diet quality as assessed by the Healthy Food Intake Index and relationship with
      serum lipoprotein particles and serum fatty acids in pregnant women at increased
      risk for gestational diabetes.
AB  - The importance of overall diet in modifying circulating lipoprotein particles and
      fatty acids during pregnancy is unclear. We examined the relationships of diet
      quality as assessed by the validated Healthy Food Intake Index (HFII) with serum
      HDL, LDL and VLDL particle concentrations and sizes and proportions of serum
      fatty acids in pregnant women at high risk for gestational diabetes mellitus
      (GDM). Overall, 161 women with a BMI of >=30 kg/m2 and/or a history of GDM were
      drawn from the Finnish Gestational Diabetes Prevention Study, which is a dietary
      and exercise intervention trial to prevent GDM. At baseline, the HFII score was
      inversely related to concentrations of HDL particles (P=0.010) and MUFA (P=0.010)
      and positively related to concentrations of n-3 (P<0.001) and n-6 (P=0.003) PUFA.
      The significance for MUFA disappeared after adjustments. An increase in the HFII
      score from the first to second trimester of pregnancy correlated with reduced
      VLDL particle size (r -0.16, 95 % CI -0.31, -0.01), decreased MUFA concentrations
      (r -0.17, 95 % CI -0.31, -0.01) and elevated n-6 PUFA concentrations (r 0.16, 95
      % CI 0.01, 0.31). In the maximum-adjusted model, the results remained significant
      except for VLDL particle size. These findings suggest that higher diet quality as
      defined by the HFII is related to a more favourable serum fatty acid profile,
      whereas the relationship with serum lipoprotein profile is limited in pregnant
      women at increased GDM risk.

PMID- 30223911
TI  - A randomised, placebo-controlled 24-week study evaluating adjunctive
      brexpiprazole in patients with major depressive disorder.
AB  - OBJECTIVE: To evaluate brexpiprazole adjunctive to antidepressant therapies
      (ADTs) as maintenance treatment in patients with major depressive disorder with
      inadequate response to ADT, utilising a novel study design. METHODS: The study
      comprised an 8-week prospective treatment period with open-label ADT with double
      blind placebo treatment and a 24-week randomised treatment period. Investigators
      and patients were blinded to treatment periods, randomisation criteria, and
      timing of randomisation. Patients with early response to open-label ADT were
      withdrawn at Week 6. Patients fulfilling criteria for inadequate response were
      randomised to ADT+brexpiprazole 1-3 mg/day, or ADT+placebo. The primary endpoint
      was full remission: Montgomery-Asberg Depression Rating Scale (MADRS) total score
      <=10 and >=50% decrease from randomisation (i.e. baseline) in MADRS total score
      for at least 8 consecutive weeks. RESULTS: The primary efficacy analysis failed
      to show a statistically significant difference between the proportions of
      patients on ADT+brexpiprazole (21.4%) and ADT+placebo (24.9%) achieving full
      remission; odds ratio: 0.83; p=0.2641. The secondary endpoint of change from
      baseline to Week 6 in MADRS total score showed no difference between
      ADT+brexpiprazole and ADT+placebo (-0.4; p=0.3259). The most frequent treatment
      emergent adverse event (TEAE) in patients receiving ADT+brexpiprazole was weight
      increased (9.5% vs. 5.0% in ADT+placebo). The incidence of TEAEs leading to
      withdrawal in the randomised treatment period was 6.3% in the ADT+brexpiprazole
      group and 3.4% in the ADT+placebo group. CONCLUSION: Adjunctive brexpiprazole did
      not differentiate from ADT+placebo on the primary endpoint of full remission. A
      number of design elements in this previously untried study design may have
      contributed to the study result. Brexpiprazole was well tolerated.

PMID- 30223912
TI  - Psychosocial services for primary immunodeficiency disorder families during
      hematopoietic cell transplantation: A descriptive study.
AB  - OBJECTIVE: Caregivers for patients undergoing hematopoietic cell transplantation
      (HCT) are susceptible to significant psychosocial distress. This cross-sectional
      study aimed to describe psychosocial support services offered and used by
      caregivers of pediatric primary immune deficiency (PID) during HCT at 35
      hospitals across North America. METHOD: Caregivers of pediatric patients with PID
      were recruited by e-mail to participate in an anonymous 140-question survey
      instrument between April and May 2016 (N = 171).ResultOf those meeting inclusion
      criteria (53%), family counseling services were only offered to fewer than half
      of caregivers (42%). Of the survey participants not offered counseling services,
      the majority desired family counseling (70%) and sibling counseling (73%). That
      said, when offered counseling, utilization rates were low, with 22% of caregivers
      using family counseling and none using sibling counseling.Significance of
      resultsThese results indicate the need to offer and tailor counseling services
      for families throughout the HCT process. Further research should focus on
      reducing barriers to utilization of counseling services such as offering bedside
      counseling services, online modalities, and/or financial assistance.

PMID- 30223913
TI  - The assertive approach to clozapine: nasogastric administration.
AB  - : Aims and methodAn 'assertive approach' to clozapine, where nasogastric
      administration is approved, is assessed through a case-load analysis to provide
      the first systematic description of its use and outcomes worldwide. RESULTS: Five
      of the most extremely ill patients with treatment-resistant schizophrenia were
      established and/or maintained on clozapine, resulting in improvements to their
      mental state; incidents were reduced, segregation was terminated and progression
      to less restrictive environments was achieved.Clinical implicationsDespite being
      underutilised and rarely enforced, in extreme circumstances, an assertive
      approach to clozapine can be justified. Nasogastric clozapine can be safely
      delivered and the approach itself, rather than actual nasogastric administration,
      may be enough to help establish and maintain patients with treatment-resistant
      schizophrenia on the most effective treatment.Declaration of interestE.S. has
      received speaker fees from Jansen Pharmaceuticals and Novartis.

PMID- 30223914
TI  - Early-life origins of disparities in chronic diseases among Indigenous youth:
      pathways to recovering health disparities from intergenerational trauma.
AB  - Indigenous women and children experience some of the most profound health
      disparities globally. These disparities are grounded in historical and
      contemporary trauma secondary to colonial atrocities perpetuated by settler
      society. The health disparities that exist for chronic diseases may have their
      origins in early-life exposures that Indigenous women and children face.
      Mechanistically, there is evidence that these adverse exposures epigenetically
      modify genes associated with cardiometabolic disease risk. Interventions designed
      to support a resilient pregnancy and first 1000 days of life should abrogate
      disparities in early-life socioeconomic status. Breastfeeding, prenatal care and
      early child education are key targets for governments and health care providers
      to start addressing current health disparities in cardiometabolic diseases among
      Indigenous youth. Programmes grounded in cultural safety and co-developed with
      communities have successfully reduced health disparities. More works of this kind
      are needed to reduce inequities in cardiometabolic diseases among Indigenous
      women and children worldwide.

PMID- 30223915
TI  - Hypoplastic left heart syndrome: from fetus to fontan.
AB  - The care of children with hypoplastic left heart syndrome is constantly evolving.
      Prenatal diagnosis of hypoplastic left heart syndrome will aid in counselling of
      parents, and selected fetuses may be candidates for in utero intervention.
      Following birth, palliation can be undertaken through staged operations: Norwood
      (or hybrid) in the 1st week of life, superior cavopulmonary connection at 4-6
      months of life, and finally total cavopulmonary connection (Fontan) at 2-4 years
      of age. Children with hypoplastic left heart syndrome are at risk of circulatory
      failure their entire life, and selected patients may undergo heart
      transplantation. In this review article, we summarise recent advances in the
      critical care management of patients with hypoplastic left heart syndrome as were
      discussed in a focused session at the 12th International Conference of the
      Paediatric Cardiac Intensive Care Society held on 9 December, 2016, in Miami
      Beach, Florida.

PMID- 30223916
TI  - Spermatic mitochondria: role in oxidative homeostasis, sperm function and
      possible tools for their assessment.
AB  - SummaryDespite sperm mitochondrial relevance to the fertilization capacity, the
      processes involved in the production of ATP and functional dynamics of sperm
      mitochondria are not fully understood. One of these processes is the paradox
      involved between function and formation of reactive oxygen species performed by
      the organelle. Therefore, this review aimed to provide data on the role of sperm
      mitochondria in oxidative homeostasis and functionality as well the tools to
      assess sperm mitochondrial function.

PMID- 30223917
TI  - A convenient identification of carbamate-derived drug substances.
AB  - The "second identification" of drugs in pharmacies and hospital pharmacies
      affords the availability of easy to perform and robust tests. Besides
      determination of melting points and simple chromatography (TLC), reliable color
      and precipitation reactions are common techniques for this purpose.
      Preferentially, these reactions allow for the identification of typical
      functional groups in the drugs. Here we present a reaction for identification of
      carbamate-type drugs, based on the precipitation of barium carbonate upon
      treating the analytes with barium hydroxide solution at 80  degrees C. This
      method works well for carbamate drugs with noteworthy water solubility like
      carbachol, neostigmine bromide, and pyridostigmine bromide, and could be
      considered as a method for second identification of these drugs in pharmacopoeias
      and in Deutscher Arzneimittel-Codex/Neues Rezeptur-Formularium (DAC-NRF).

PMID- 30223918
TI  - Isolation and characterization of the acid and base degradation products of
      andrographolide.
AB  - Andrographolide was subjected to degradation under acidic and basic conditions.
      Three degradation products including two novel compounds, 8,9
      didehydroandrographolide (AG-A) and 15-seco-andrographolide (AG-B2), and a known
      product, 14-deoxy-11,12-didehydroandrographolide (AG-B1), were isolated by
      chromatography and identified on the basis of their NMR and MS data. The
      degradation product, AG-A, may result from the isomerization of andrographolide
      under acidic conditions whereas the base degradation products, AG-B1 and AG-B2,
      were formed most likely due to the dehydration of allyl alcohol and the
      hydrolysis of andrographolide at the lactone ring, respectively.

PMID- 30223919
TI  - HPLC electrochemical detection and quantification of monoamines and their
      metabolites in rat brain tissue samples.
AB  - The monitoring of monoamines and their metabolites in CNS samples can be very
      valuable in pharmaceutical and biomedical research. A specific high performance
      liquid chromatography, coupled to a coulometric electrochemical detection method,
      for the assay of monoamines (dopamine, norepinephrine, epinephrine and serotonin)
      and their metabolites in rat brain tissue samples was developed. The
      chromatographic separation was achieved on a C8 reversed phase column with a
      mobile phase consisting of 0.1 M sodium formate buffer, 5 mM sodium 1
      heptanesulfonate, 0.17 mM ethylenediaminetetraacetic acid disodium salt and 5%
      v/v acetonitrile (pH +/-4.0). The detection was achieved through electrochemical
      detection, with a coulometric cell potential setting of +650 mV. The flow-rate
      was at 1 ml/min and the total run time was 50 min. The method was validated
      according to validation guidelines. The method was found to be linear (R2 > 0.99)
      over the analytical range (5 to 200 ng/ml) for all monoamines and their
      metabolites. All the other validation parameters were acceptable and within
      range. The method was applied to three rat brain areas (pre-frontal cortex,
      hippocampus and striatum), where the monoamines (except for epinephrine) and
      their metabolites were easily detected.

PMID- 30223920
TI  - The use of experimental design for the development and validation of an HPLC-ECD
      method for the quantitation of efavirenz.
AB  - A high performance liquid chromatography with electrochemical detection (HPLC
      ECD) method for the quantitation of efavirenz (EFV) was developed, since
      traditional HPLC-UV methods may be inappropriate, given that EFV undergoes
      photolytic degradation following exposure to UV light. This work describes the
      use of response surface methodology (RSM) based on a central composite design
      (CCD) to develop a stability-indicating HPLC method with pulsed ECD in direct
      current (DC) mode at an applied potential difference and current of +1400 mV and
      1.0 MUA for the analysis of EFV. Separation of EFV and imipramine was achieved
      using a Nova-Pak(r)C18 cartridge column and a mobile phase of phosphate buffer
      (pH 4.5): acetonitrile (ACN) (55:45 v/v). Mobile phase pH, buffer molarity, ACN
      concentration and applied potential difference were investigated. The optimized
      method produced sharp well resolved peaks for imipramine and EFV with retention
      times of 3.70 and 8.89 minutes. The calibration curve was linear (R2 = 0.9979)
      over the range 5-70 MUg/mL. Repeatability and intermediate precision ranged
      between 3.37 and 4.34 % RSD and 1.31 and 4.29 % RSD and accuracy between -0.80
      and 4.71 % bias. The LOQ and LOD were 5.0 and 1.5 MUg/mL. The method was specific
      for EFV and was used to analyse EFV in commercially available tablets. The HPLC
      ECD method is more suitable for quantitative analysis of EFV than HPLC-UV.

PMID- 30223921
TI  - An effective quantitative fingerprint method for evaluating the quality
      consistency of Desmodium styracifolium.
AB  - An HPLC method for combined quantification of five major constituents (vicenin-1,
      schaftoside, isoschaftoside, vicenin-3 and isovitexin) of Desmodium styracifolium
      was developed to evaluate the quality consistency of this medicinal herb. The
      chromatographic separation was accomplished on an Agilent 5 TC-C18 column (4.6 *
      250 mm, 5 MUm) with gradient elution using acetonitrile and 0.1 % aqueous formic
      acid (v/v). The column temperature was 30  degrees C and the detection wavelength
      was 272 nm. The chromatographic data were analyzed with a novel systematic
      quantitative fingerprint method (SQFM). The established quantitative fingerprint
      method was successfully applied to simultaneously determine the levels of the
      major constituents, and 39 common peaks were found. The samples collected in
      Guangdong province had a good quality consistency, in accordance with the
      traditional opinion that Guangdong province is the best region for cultivation of
      D. styracifolium. The fingerprint-antioxidant efficacy relationship of the
      different samples was investigated by examining the correlation between the
      common peaks and the antioxidant effect. Twenty-two common peaks were positively
      correlated with the antioxidant effect, while the others showed a negative
      correlation. This quantitative fingerprint method could be considered as a
      suitable approach to evaluate the quality of traditional Chinese medicines and
      herbal preparations. The SQFM was reliable and efficient for analysis of the
      chromatographic data.

PMID- 30223922
TI  - Telmisartan regulates the development of cerebral ischemia by alleviating
      endoplasmic reticulum stress.
AB  - Recent studies have shown that telmisartan (TMS) is effective for the protection
      against ischemia/brain damage in rat models. However, the specific underlying
      mechanism is poorly understood. In line with previous results, our data showed
      that TMS improves CBF and physiological variables, including pH, pCO2, pO2.
      Through CD31 immunofluorescence staining, reduction of blood vessel density was
      found in MCAO group, but TMS treatment could enhance the cerebral vascular
      density in the ischemic area. Meanwhile, TMS treatment could enhance the number
      of BrdU/lectin double-positive cells. Furthermore, the reduction of nestin
      positive cells was identified in the brain of MCAO rats, while the number of
      nestin-positive cells was significantly increased after TMS administration.
      Furthermore, the expression of ERS-related proteins, including GRP78,
      CHOP/GADD153, Caspase12 was increased after MCAO, but was decreased after
      administration of TMS, thereby enhancing angiogenesis and neuron regeneration.

PMID- 30223923
TI  - Immunomodulatory and anti-inflammatory effects of total flavonoids of Astragalus
      by regulating NF-KappaB and MAPK signalling pathways in RAW 264.7 macrophages.
AB  - Astragalus membranaceus Bunge has long been used to improve immune function in
      traditional Chinese medicine. The total flavonoids of Astragalus (TFA) are the
      main active components isolated from Astragalus membranaceus Bunge. Our recent
      study has shown that TFA has in vivo and in vitro immunomodulatory and anti
      inflammatory effects; however, its potential mechanisms have not yet been
      elucidated. The present study aims to confirm the immunomodulatory and anti
      inflammatory mechanisms of the action involved. Murine RAW 264.7 macrophages were
      treated with 10, 25 and 100 MUg/ml of TFA. The mRNA expression levels of the
      tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1beta, IL-10,
      inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were examined
      by RT-PCR in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The
      protein expression levels of iNOS and COX-2, in addition to the phosphorylations
      of proteins in the mitogen activated protein kinase (MAPK) and nuclear factor
      (NF)-kappaB signalling pathways were measured by Western blot in LPS-stimulated
      RAW 264.7 macrophages. The results showed that TFA significantly inhibited TNF
      alpha, IL-1beta, IL-6, iNOS and COX-2 mRNA levels and increased IL-10 mRNA level
      in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. Further studies
      revealed that TFA significantly inhibited iNOS and COX-2 protein levels, the
      phosphorylations of p38 and JNK in MAPKs pathway and IKKalpha/beta, IkappaBalpha
      and the expression of nuclear NF-kappaB p65 in NF-kappaB pathway in LPS
      stimulated RAW 264.7 cells. It suggests that TFA possesses immunomodulatory and
      anti-inflammatory effects by regulating MAPK and NF-KappaB signalling pathways in
      RAW 264.7 macrophages.

PMID- 30223924
TI  - Andrographolide inhibits proliferation and induces apoptosis of nasopharyngeal
      carcinoma cell line C666-1 through LKB1-AMPK-dependent signaling pathways.
AB  - BACKGROUND: Andrographolide (Andro) belongs to the main bioactive ingredients of
      Andrographis paniculata. Many studies have shown that andro has a variety of
      pharmacological activities such as anti-inflammatory, anti-bacterial, anti-virus,
      anti-oxidant, immune regulation and liver protective effects. Moreover andro has
      been reported to have anticancer activity in multiple types of cancer, including
      gastric cancer, breast cancer, lung cancer and so on. However, there is no report
      about the effect of andro on the human NPC cell line C666-1 and the molecular
      mechanisms of andro-mediated apoptosis in C666-1 cells remain to be clarified.
      METHODS: Cell proliferation was measured by a CCK8 assay, cell apoptosis rate was
      evaluated by flow cytometric analysis, and the protein expression of LKB1/AMPK
      signaling pathways was detected by Western blotting. RESULTS: Treatment with
      andro inhibited cell proliferation and induced apoptosis of C666-1 cells.
      Moreover, andro could activate LKB1-AMPK signaling. We also demonstrated that
      Ca2+/calmodulin-dependent protein kinase kinasebeta (CaMKKbeta) was not involved
      in the regulation of andro on AMPK activation in C666-1 Cells. CONCLUSIONS: Andro
      suppressed proliferation and induced apoptosis of C666-1 cells through regulating
      the LKB1/AMPK/mTOR signal pathway.

PMID- 30223925
TI  - Factors influencing the use of over-the-counter drugs and health
      foods/supplements.
AB  - Over-the-counter (OTC) drugs and health foods/supplements are used as means of
      self-medication with the aim of preventing diseases and maintaining health. No
      reports have yet addressed the relationship between healthcare systems and self
      medication. Here, we carried out a retrospective survey to identify healthcare
      system factors affecting OTC drug and health food/supplement usage. Patients
      hospitalized at Gifu Municipal Hospital between October 1, 2014 and March 31,
      2015 were given a survey. The items surveyed were age, gender, disease, alcohol
      intake/smoking status, insurance classification, and medical pharmaceuticals, OTC
      drugs, and health foods/supplements used immediately before hospitalization. We
      performed multiple logistic regression analysis using OTC drugs and health
      foods/supplements as dependent variables with patient attributes, medical
      insurance, etc. as independent variables. A total of 5,965 patients were
      analyzed. OTC users comprised 2.6 % (156 people) of the total. The use of OTC
      drugs was significantly higher for females and alcohol consumers than in other
      categories. In contrast, the use of OTC drugs was significantly lower for
      participants in public expense/medical subsidy programs. Health foods/supplements
      were used by 4.0 % of all subjects (240 people); their use was significantly
      higher among females and users of medical pharmaceuticals. On the other hand, the
      use of health foods/supplements was significantly lower for smokers, users of the
      latter-stage elderly healthcare system, and users of public expense/medical
      subsidy programs.

PMID- 30223926
TI  - Incompatibilities in paediatric intensive care - pitfalls in drug information.
AB  - Drug incompatibilities can lead to loss of effectiveness of drugs or to increased
      risk for undesirable effects that can even be life-threatening. Especially
      children are at high risk. Databases are an important source of information in
      routine care to avoid incompatibilities. However, they were supposedly developed
      considering drugs for use in adults. Thus, we analysed to what extent databases
      are appropriate for the identification of incompatibilities in intravenous (i.v.)
      drug therapy in paediatric intensive care. We analysed the information provided
      by two databases (Database A and B) on all pairs of two drugs prescribed to be
      administered via the same i.v. access line in a university paediatric intensive
      care unit during the study period of 50 days. A total of 50 different i.v. drugs
      was prescribed in 318 different combinations (drug pairs). We found information
      on (in)compatibilities in 23.0 % (73/318) in Database A and in 31.1 % (99/318) in
      Database B. Only in 11.0 % (35/318) of the drug pairs, both databases provided
      information. Considering those drug pairs, in 17.1 % (6/35) Database B indicated
      compatibility whereas Database A indicated incompatibility. Compatibility
      information delivered by databases on drugs used in paediatric intensive care is
      incomplete, heterogeneous, and partly contradictory. Thus, an increased awareness
      on the strengths and limitations of different databases is necessary to avoid
      patient harm.

PMID- 30223927
TI  - Relationship between medication adherence and glycemic control in Japanese
      patients with type 2 diabetes.
AB  - A cross-sectional survey of 358 patients was conducted among type 2 diabetes
      patients recruited at medical institutions or via an online research company.
      Medication adherence was measured using the 8-item Morisky Medication Adherence
      Scale (MMAS-8). Univariate and multivariate regression analyses of glycosylated
      hemoglobin (HbA1c) were performed in addition to assessing demographic and
      disease characteristics and MMAS-8. In conclusion, medication adherence as
      measured by the MMAS-8 score independently contributes to altering the HbA1c
      level in the range of 1.12 %. The number of medications prescribed and insulin
      use are also related to HbA1c.

PMID- 30223928
TI  - Efficacy of pegfilgrastim administration in patients with esophageal cancer
      treated with docetaxel, cisplatin, and 5-fluorouracil.
AB  - Chemotherapy is among the standard treatments for esophageal cancer. The
      docetaxel, 5-fluorouracil, and cisplatin (DCF) protocol yields a better response
      rate than 5-fluorouracil plus cisplatin. However, the incidence of side effects,
      such as febrile neutropenia and hematologic toxicity, is also significantly high
      with the DCF protocol. The granulocyte colony-stimulating factor and
      pegfilgrastim are prophylactically administered to prevent febrile neutropenia.
      This retrospective study evaluated the efficacy and safety of pegfilgrastim in
      patients receiving DCF therapy. Of the 65 patients who were administered DCF
      therapy in our hospital from 2011 through 2016, 21 received pegfilgrastim 24
      hours or more after the end of chemotherapy. The protocol comprised 70 mg/m2 each
      of docetaxel and cisplatin on day 1 and 700 mg/m2 5-fluorouracil on days 1 to 5
      via intravenous injection in a 3-week cycle. The primary endpoint was the rate of
      grade 3-4 neutropenia and febrile neutropenia. The mean patient age was 66.4
      years. The incidence of grade 3 and 4 neutropenia was 14.2 % and 11.4 %,
      respectively, in the pegfilgrastim group and 31.9 % and 37.8 %, respectively, in
      the non-pegfilgrastim group. The incidence of febrile neutropenia in the
      pegfilgrastim group and non-pegfilgrastim group was 11.4 % and 40.3 %,
      respectively. Statistical analysis showed that the incidence of neutropenia and
      febrile neutropenia was significantly different (p<0.05) between the two groups.
      Pegfilgrastim prevents severe neutropenia and febrile neutropenia in patients
      with esophageal cancer who are treated according to the DCF protocol.

PMID- 30223929
TI  - JQ1: a novel potential therapeutic target.
AB  - The bromo- and extra-terminal domain (BET) signaling pathway plays an important
      role in cell proliferation, immune responses, and pro-inflammatory events. JQ1 as
      a first-in-class potent and selective inhibitor of the BRD4 signaling pathway is
      widely used for tumor biology studies. It was found that JQ1 could potently
      reduce cancer cell viability in vitro and in vivo. The underlying mechanisms
      include an effect on cell cycle arrest in the G1 phase and a decrease in the
      percentage of cells in the S phase. Furthermore, JQ1 could alter cytokines
      expressions not only in T cells but also in dendritic cells (DCs). Apoptosis of
      tumor cells was induced by JQ1 through downregulation of E2f1 protein expression.
      In addition, JQ1 exhibited a potent suppressive effect on ERalpha and androgen
      receptor (AR) signaling pathways in breast and prostate cancers. Accumulating
      evidence supports the notion of BRD4 suppression as a target of therapeutic
      intervention in clinical oncology. Our present review article advances the
      understanding of the role of the JQ1 / BRD4 protein.

PMID- 30223930
TI  - Synthesis and characterization of four process impurities in pazopanib.
AB  - Pazopanib (trade name Votrient(r)) is a potent and selective multi-targeted
      tyrosine kinase inhibitor that blocks tumor growth and inhibits angiogenesis.
      Based on a recently reported procedure, we herein report the first synthesis of
      four potential process impurities generated in the production of pazopanib. The
      structure of these impurities were synthesized and characterized by 1H NMR, 13C
      NMR and HRMS data. The possible formation mechanisms of these impurities were
      also elucidated. These findings should be useful for the quality control of
      pazopanib in manufacture.

PMID- 30223931
TI  - Development of a novel celecoxib-loaded nanosuspension using a wet media milling
      process.
AB  - To develop a novel celecoxib (CXB)-loaded drug delivery system, numerous
      nanosuspensions were prepared with various polymers and surfactants using a wet
      media milling process, and their particle sizes were subsequently determined. A
      24 full factorial design was used to identify the most appropriate preparation
      conditions. Pharmacokinetics of the selected nanosuspension were performed in
      rats and compared with those of a drug powder and a commercial CXB-loaded
      product. Among the carriers investigated, copovidone and sodium lauryl sulphate
      gave the smallest particle size of the drug in the nanosuspension. In particular,
      the nanosuspension prepared with 5% CXB, 4% copovidone, and 0.1% sodium lauryl
      sulphate, under the appropriate conditions, showed a particle size of
      approximately 190 nm, which was physically stable for at least 8 weeks. This
      nanosuspension provided a significantly higher plasma concentration and AUC in
      rats as compared with the drug powder and the commercial product. Thus, this
      novel CXB-loaded nanosuspension is a promising candidate with excellent stability
      and enhanced oral bioavailability.

PMID- 30223932
TI  - Effects of the antiretroviral drug 2'-deoxy-2'-beta-fluoro-4'-azidocytidine (FNC)
      on P-gp, MRP2 and BCRP expressions and functions.
AB  - The purpose of the present study was to dig into recent studies designed to
      characterize the impacts of 2'-deoxy-2'-beta-fluoro-4'-azidocytidine (FNC) on P
      glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast
      cancer resistance protein (BCRP). Specifically, the modulation effects of FNC on
      P-gp, MRP2 and BCRP protein expressions were assessed by western blot methods. 5
      (and 6)-Carboxy-2',7'-dichloroflourescein (CDF) and BODIPY-prazosin were used to
      provide indications of alterations of MRP2 and BCRP activities. The effects of P
      gp, MRP2 and BCRP on FNC were evaluated in the in situ single-pass intestinal
      perfusion model. The results showed that FNC at higher concentrations and with
      longer incubation times can upregulate the protein expression of P-gp, MRP2 and
      BCRP in Caco-2 cells. The upregulated proteins were also functionally active, as
      revealed by a lower degree of CDF and BODIPY-prazosin uptake by the cell
      monolayers. The intestinal absorptive coefficient (Peff) was observed to
      significantly increase with the inhibitors of P-gp, MRP2 and BCRP. These results
      suggested that FNC could modulate the expressions and functions of P-gp, MRP2 and
      BCRP, while P-gp, MRP2 and BCRP were involved in the efflux transport of FNC. The
      inductive effects of FNC on P-gp, MRP2 and BCRP suggested the possibility of FNC
      to contribute to the inter- and intra-individual variability of itself, as well
      as to alter the absorption of other drugs that may be administered concomitantly.

PMID- 30223933
TI  - Cardamonin protects against adverse cardiac remodeling through mTORC1 inhibition
      in mice with myocardial infarction.
AB  - The mTORC1-dependent signaling pathway is mainly involved in the adverse left
      ventricular remodeling (ALVR) process after myocardial infarction (MI). However,
      whether mTORC1 inhibition by cardamonin attenuates ALVR after MI is still not
      reported. Twenty mice were randomly assigned into three groups: sham group (10
      ml/kg/day PBS, n=6), model group (MI and 10 ml/kg/day PBS, n=7) and cardamonin
      treated group (MI and 20 mg/kg/day cardamonin, n=7). All groups received an
      intraperitoneal injection accordingly for two weeks. Heart and body mass were
      measured. Cardiac function was assessed by echocardiography. The collagen
      deposition, area of cardiomyocytes and cell apoptosis of border area were
      evaluated using Masson's staining, WGA staining and TUNEL assay, respectively.
      The 4E-binding protein 1 (4E-BP1) and ribosomal S6 (S6) in myocardium were
      determined by western blot. mTOR-Raptor association was tested by co
      immunoprecipitation assay in H9C2 cell line. Treatment with cardamonin, MI mice
      displayed that heart hypertrophy and heart dysfunction were alleviated, and
      cardiac fibrosis, cardiomyocyte size and cell apoptosis of border area were
      decreased (P<0.05). Besides, cardamonin can inhibit 4E-BP1 and S6 phosphorylation
      in heart of MI mice and H9C2 cell line (P<0.05). Furthermore, cardamonin
      disrupted mTOR-Raptor association in vitro. Cardamonin exerted cardio-protection
      against ALVR through mTORC1 inhibition.

PMID- 30223934
TI  - Downregulation of microRNA-128-3p protects human esophageal squamous Het-1A cells
      from hydrochloric acid-induced cell injury by targeting E2F3.
AB  - This study aimed to investigate the role of microRNA-128-3p in regulating
      hydrochloric acid (HCl)-induced cell injury in human esophageal squamous Het-1A
      cells. Het-1A cells were treated with HCl (pH 4.0) to induce esophageal injury
      like this caused by reflux. Whether HCl induced cell injury was then assessed by
      detecting cell proliferation and apoptosis. The expression of miR-128-3p in HCl
      treated Het-1A cells was investigated, followed by investigating the effects of
      miR-128-3p overexpression and suppression on HCl-induced Het-1A cell injury. In
      addition, the target of miR-128-3p was identified. Besides, the association
      between miR-128-3p and ERK and PI3K/AKT pathways was further explored. HCl
      inhibited the proliferation and increased apoptosis of Het-1A cells. miR-128-3p
      was upregulated in Het-1A cells after HCl treatment. Inhibition of miR-128-3p
      alleviated HCl-induced Het-1A cell injury, whereas miR-128-3p overexpression
      further aggravated this injury. Moreover, E2F3 was confirmed as a target of miR
      128-3p, which could be negatively regulated by miR-128-3p. Besides, miR-128-3p
      inhibition remarkably alleviated the inhibitory effects of HCl on the activation
      of ERK and PI3K/AKT pathways, which were further reversed after inhibition of miR
      128-3p and E2F3 at the same time. Alltogether, our findings indicate that
      downregulation of microRNA-128-3p may protect human esophageal squamous cells Het
      1A from HCl-induced cell injury via targeting E2F3 and inhibiting the activation
      of ERK and PI3K/AKT pathways. These findings provide the experimental basis for
      targeted treatment of reflux esophagitis.

PMID- 30223935
TI  - Effect of miR-433-3p and miR-883b-5p on murine CYP 3A family enzymes in AML12
      cells.
AB  - Here we searched for microRNAs that could interact with cytochrome P450 (CYP)
      enzymes in silico, and then investigated their effects on Cyp gene expressions
      using the cultured mouse liver cell line AML12. Among the mouse Cyp3a genes, some
      miRNAs were found to interact with Cyp3a11, 13, 16, and 44 by the in silico
      analysis using the miRWalk2.0 database. In addition to this software, which
      included twelve miRNA target prediction algorithms, we also applied our in-house
      developed Excel VBA algorithm to obtain predictions more efficiently. Finally,
      two miRNAs, miR-433-3p and miR-883b-5p, were extracted as candidates that
      interact with Cyp3a genes. To evaluate the effects of these miRNAs on Cyp3a gene
      expression, we first examined whether they actually interacted with the Cyp3a 3'
      untranslated region (3'-UTR) using a luciferase assay system in AML12 cells. We
      then evaluated whether the expression of each miRNA affected the expression of
      Cyp3a mRNAs and their transcribed proteins. We found that the transiently
      expressed miRNAs significantly reduced the reporter activity of the Cyp3a 3'-UTR
      site in AML12 cells. In addition, the mRNA and protein expressions of the
      corresponding Cyp3as were significantly decreased in the miRNA-treated AML12
      cells. Using cultured cells, we clearly demonstrated that miR-433-3p and miR-883b
      5p, which were identified by in silico prediction, actually bind to Cyp3a mRNAs
      and regulate Cyp gene expressions.

PMID- 30223936
TI  - Therapeutic potential of artesunate in experimental autoimmune myasthenia gravis
      by upregulated T regulatory cells and regulation of Th1/Th2 cytokines.
AB  - Artesunate is a semi-synthetic derivative of a Chinese herb named Artemisia annua
      L. that is commonly used as an antimalarial agent in the history of traditional
      Chinese medicine. Many studies have reported artesunate possesses anti
      inflammatory and immunoregulation properties. The present study was conducted to
      explore whether artesunate was effective in experimental autoimmune myasthenia
      gravis (EAMG) in Lewis rats. Our data showed that artesunate could improve the
      clinical symptoms and suppress the development of EAMG. Artesunate exerted its
      immunomodulatory effects by inhibiting lymphocyte proliferation and the
      expression of costimulatory molecules CD86, modulating Th1/Th2 cytokine
      expression levels, and enhancing the level of Treg cells. The final result of
      administration of artesunate was the decreased synthesis of anti-R97-116 IgG,
      IgG2a, and IgG2b antibodies. The treatment effect of artesunate was more obvious
      at dose of 10 mg/kg. These date suggest that artesunate might be a potential drug
      for the treatment of human myasthenia gravis (MG).

PMID- 30223937
TI  - HIF-1alpha-induced autophagy contributes to cisplatin resistance in ovarian
      cancer cells.
AB  - In this study, the viability and apoptosis of ovarian cancer cell line OVCAR-3
      were assessed using MTT and flow cytometry analysis. GFP-tagged LC3 plasmid
      transfection was utilized to demonstrate the occurrence of autophagy. The
      expression of HIF-1alpha, Beclin1, LC3 and beta-actin were determined with
      Western blot analysis. We found that hypoxia could inhibit cisplatin induced
      apoptosis in OVCAR-3 cells and enhance the chemoresistance to cisplatin.
      Furthermore, GFP-tagged LC3 plasmid transfection and western blot were used to
      demonstrate that hypoxia induced chemoresistance of OVCAR-3 cells to cisplatin is
      related to HIF-1alpha-induced autophagy. All these findings suggest that the
      cisplatin resistance of ovarian cancer cells is associated with HIF-1alpha
      induced autophagy.

PMID- 30223938
TI  - Attenuation of pro-inflammatory cytokines and oxidative stress by misoprostol in
      renal ischemia/reperfusion in rats.
AB  - The ischemia/reperfusion (I/R) process alters metabolic pathways, releasing
      reactive oxygen species and pro-inflammatory cytokines that cause tissue necrosis
      and activate cellular apoptotic pathways. Misoprostol (MSP) is a prostaglandin E1
      analog that has demonstrated a cytoprotective role in the I/R process. The study
      objective was to evaluate the effects of MSP on the regulation of pro
      inflammatory and oxidative stress mediators in an I/R-induced acute kidney injury
      rat model. Wistar rats were divided into 3 groups. Sham and I/R were given 1
      mL/day of physiological solution; MSP+I/R was given intragastric MSP (300 MUg/kg)
      for 3 days. For I/R and MSP+IR, the renal hilum was clamped for 45 min, followed
      by 15 h of reperfusion. Renal function tests, pro-inflammatory cytokines,
      mediators of oxidative stress, and histological analysis were evaluated. Pro
      inflammatory cytokine activity was significantly attenuated in the MSP+I/R group.
      However, there was no statistically significant difference between Sham and MSP.
      Regarding antioxidant activity, MSP+I/R showed a significant decrease in these
      mediators compared with Sham and I/R. Histologically, scarce medullary necrosis
      was observed with a preserved renal cortex in the MSP group.

PMID- 30223939
TI  - Anti-inflammatory effects of neferine on LPS-induced human endothelium via MAPK,
      and NF-kappabeta pathways.
AB  - This study aimed to evaluate the anti-inflammatory mechanism of neferine, a
      bisbenzylisoquinoline alkaloid, on the lipopolysaccharide (LPS)-induced
      inflammation in Human Umbilical Endothelial Cells (HUVECs) and pulmonary aorta
      cells. Production of pro-inflammatory cytokines and nitric oxide (NO) was
      determined using Griess reaction in human endothelial cells. The levels of
      inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen
      activated protein kinases (MAPKs) were analyzed using real time PCR and western
      blotting. Neferine significantly prevented the NO, TNF-alpha, COX-2, iNOS, IL-1B,
      and other inflammatory mediators formation in increasing dose as compared to LPS
      induced human endothelial cells. The expressions of NADPH oxidase subunits
      p22phox, p47phox, and gp91phox were increased in LPS-induced HUVECs but neferein
      was able to reverse the effect in a dose-dependent manner. The anti-inflammatory
      effects of neferine in LPS-induced endothelial cells are attributed through the
      modulation of MAPK and NF-kappabeta pathways. Collectively, these results suggest
      that neferine could be beneficial in the early treatment of atherosclerosis to
      prevent stroke and heart disease.

PMID- 30223940
TI  - Clinic-level factors associated with collaboration with community pharmacies in
      Japan.
AB  - The aim of this study was to clarify the clinic-level factors related to
      experiences of and attitudes toward collaboration with community pharmacies. We
      conducted a postal questionnaire survey of all clinics in Gifu, Japan, assessing
      the experiences and attitudes of representative clinical staff regarding the
      following activities in collaboration with community pharmacists: regional care
      meetings/service adjustment meetings, case study conferences, joint
      workshops/continuing education conferences, community services, information
      sharing through medical cooperation networks, and accompanying community
      pharmacists during home care. The factors significantly related to experiences of
      joint workshops/continuing education conferences included home care visits (odds
      ratio [OR] 2.39) and a 100 % out-of-hospital prescription ratio (OR 4.80). In
      contrast, only home care visits were significantly associated with consideration
      of information sharing through medical cooperation networks and accompanying
      community pharmacists during home care (OR 2.06 and 11.91, respectively).
      Finally, the factors significantly associated with considering implementing case
      study conferences and joint workshops/continuing education conferences included
      home care visits (OR 4.64 and 2.98, respectively) and a 100% out-of-hospital
      prescription ratio (OR 4.64 and 6.38). Overall, having more opportunities to
      communicate with community pharmacists and other healthcare professionals
      appeared to facilitate clinics' consideration of collaboration with community
      pharmacies, along with actual experiences.

PMID- 30223941
TI  - Sperm-mediated DNA lesions alter metabolite levels in spent embryo culture
      medium.
AB  - Paternal genetic alterations may affect embryo viability and reproductive
      outcomes. Currently it is unknown whether embryo metabolism is affected by sperm
      mediated abnormalities. Hence, using a mouse model, this study investigated the
      response to paternally transmitted DNA lesions on genetic integrity and
      metabolism in preimplantation embryos. Spent embryo culture media were analysed
      for metabolites by nuclear magnetic resonance spectroscopy and embryonic genetic
      integrity was determined by terminal deoxynucleotidyl transferase dUTP nick-end
      labelling (TUNEL) assay on embryonic Day 4.5 (E4.5). Metabolic signatures were
      compared between normally derived embryos (control) and embryos derived from
      spermatozoa carrying induced DNA lesions (SDL). SDL embryos showed a significant
      reduction in blastocyst formation on E3.5 and E4.5 (P < 0.0001) and had an
      approximately 2-fold increase in TUNEL-positive cells (P < 0.01). A cohort of SDL
      embryos showing delayed development on E4.5 had increased uptake of pyruvate (P <
      0.05) and released significantly less alanine (P < 0.05) to the medium compared
      with the corresponding control embryos. On the other hand, normally developed SDL
      embryos had a reduced (P < 0.001) pyruvate-to-alanine ratio compared with
      normally developed embryos from the control group. Hence, the difference in the
      metabolic behaviour of SDL embryos may be attributed to paternally transmitted
      DNA lesions in SDL embryos.

PMID- 30223942
TI  - Physiotherapy clinical education in Australia: an exploration of clinical
      educator characteristics, confidence and training requirements.
AB  - Objectives The aim of this study was to describe physiotherapists' involvement,
      confidence and training needs in the provision of student clinical education (CE)
      in Australia.Methods A valid and reliable cross-sectional online survey
      instrument was used to collect data from physiotherapists employed in public and
      private healthcare facilities in Australia. Survey questions included participant
      personal and professional characteristics, participation in CE-related continuing
      professional development (CPD) and confidence in components of CE.Results In all,
      170 (34%) physiotherapists (mean age 37 years; mean years clinical experience 13
      years) completed the survey. Most participants (68%) were currently involved in
      CE, over half (56%) had completed CE-related CPD and many (56%) reported a need
      for more CPD. Participants with no previous CE experience were less confident (P
      <= 0.05) in all components of CE. Participants with less clinical experience were
      less confident in managing challenging students (P = 0.003), multiple students (P
      = <0.001) and competing workplace and education duties (P = <0.001).Conclusions
      Physiotherapists with varying professional characteristics were involved in CE.
      Although many participants had attended CE-related CPD, many reported that more
      training was required. Future training for clinical educators should be tailored
      to participants' level of experience and focus on the components of CE in which
      they feel least confident.What is known about the topic? The ability of
      physiotherapists to confidently assume a clinical educator role may affect their
      willingness to be clinical educators in the future and the students' perceptions
      of clinical placement quality. CPD relating to CE may help prepare
      physiotherapists for the clinical educator role.What does this paper add? There
      is a lack of information regarding physiotherapists' involvement in CE,
      completion of CE-related CPD or perceived levels of confidence in various aspects
      of the clinical educator role, such as placement organisation, teaching,
      assessment and the provision of feedback. This study describes the involvement of
      physiotherapists in CE in Australia, including their demographic and professional
      characteristics, participation in CE-related CPD and confidence in various
      components of CE.What are the implications for practitioners? Several
      recommendations regarding future CE-related CPD have resulted from this study,
      including tailoring CPD to the needs of physiotherapists based on their level of
      clinical or CE experience, focusing CPD on the aspects of CE in which
      physiotherapists feel least confident and raising the awareness of and improving
      accessibility to CPD opportunities in this area.

PMID- 30223943
TI  - CRISPR knockouts reveal an endogenous role for ancient neuropeptides in
      regulating developmental timing in a sea anemone.
AB  - Neuropeptides are evolutionarily ancient peptide hormones of the nervous and
      neuroendocrine systems, and are thought to have regulated metamorphosis in early
      animal ancestors. In particular, the deeply conserved Wamide family of
      neuropeptides-shared across Bilateria (e.g. insects and worms) and its sister
      group Cnidaria (e.g. jellyfishes and corals)-has been implicated in mediating
      life-cycle transitions, yet their endogenous roles remain poorly understood. By
      using CRISPR-Cas9-mediated reverse genetics, we show that cnidarian Wamide
      referred to as GLWamide-regulates the timing of life cycle transition in the sea
      anemone cnidarian Nematostella vectensis. We find that mutant planula larvae
      lacking GLWamides transform into morphologically normal polyps at a rate slower
      than that of the wildtype control larvae. Treatment of GLWamide null mutant
      larvae with synthetic GLWamide peptides is sufficient to restore a normal rate of
      metamorphosis. These results demonstrate that GLWamide plays a dispensable,
      modulatory role in accelerating metamorphosis in a sea anemone.

PMID- 30223945
TI  - Special Issue: Neural basis of motivation and cognitive control.

PMID- 30223946
TI  - From the Editor's Desk...: October 2018.

PMID- 30223947
TI  - Subchondroplasty: Treatment of Bone Marrow Lesions in the Lower Extremity.
AB  - Bone marrow lesions are associated with pain, disease progression, and cartilage
      loss in inflammatory and noninflammatory conditions, and are related to
      mechanical loading and subchondral stress. Treatment, particularly in the foot
      and ankle, is challenging. In the subchondroplasty procedure, flowable,
      synthetic, calcium phosphate bone filler is injected into the defect region,
      improving subchondral bone integrity and allowing remodeling back into healthy
      cancellous bone. The procedure is a promising treatment option for bone marrow
      lesions, particularly in the foot and ankle. The benefits are a minimally
      invasive procedure with early return to weightbearing.

PMID- 30223948
TI  - Resorbable Polymer Pin Inserted with Ultrasound Activated BoneWelding Technique
      Compared with a Screw for Osteotomy Fixation in the Reverse L Bunion Correction.
AB  - Screw fixation of an osteotomy in the first metatarsal for bunion correction
      represents a compromise. The need to return to the operating room for removal
      exposes patients to added anesthesia risk, expense, time, and possible surgical
      complications. This article compares screw fixation with a novel new
      bioresorbable polymer pin that is inserted with an ultrasound activated
      BoneWelding technique to fixate a bunion correction using a reversed L osteotomy.
      This article reviews and discusses the present benefits of a time-tested
      osteotomy that, when fixated with this polymer and BoneWelding technique, offers
      new solutions for a compromised patient population.

PMID- 30223949
TI  - Minimally Invasive Bunion Correction.
AB  - Hallux valgus is a common condition that results in lateral deviation of the
      hallux and medial deviation of the metatarsal. When conservative management
      fails, surgical management is often necessary. More than 150 procedures have been
      described, and most recommend an open approach. More recently, a minimally
      invasive approach to bunion correction has gained popularity among surgeons. The
      authors have been performing a minimally invasive percutaneous method of bunion
      correction with positive outcomes. This article presents case examples and a
      systematic approach for correction of this common foot condition.

PMID- 30223944
TI  - Six domesticated PiggyBac transposases together carry out programmed DNA
      elimination in Paramecium.
AB  - The domestication of transposable elements has repeatedly occurred during
      evolution and domesticated transposases have often been implicated in programmed
      genome rearrangements, as remarkably illustrated in ciliates. In Paramecium,
      PiggyMac (Pgm), a domesticated PiggyBac transposase, carries out developmentally
      programmed DNA elimination, including the precise excision of tens of thousands
      of gene-interrupting germline Internal Eliminated Sequences (IESs). Here, we
      report the discovery of five groups of distant Pgm-like proteins (PgmLs), all
      able to interact with Pgm and essential for its nuclear localization and IES
      excision genome-wide. Unlike Pgm, PgmLs lack a conserved catalytic site,
      suggesting that they rather have an architectural function within a multi
      component excision complex embedding Pgm. PgmL depletion can increase erroneous
      targeting of residual Pgm-mediated DNA cleavage, indicating that PgmLs contribute
      to accurately position the complex on IES ends. DNA rearrangements in Paramecium
      constitute a rare example of a biological process jointly managed by six distinct
      domesticated transposases.

PMID- 30223950
TI  - 3D Printed Total Talar Replacement: A Promising Treatment Option for Advanced
      Arthritis, Avascular Osteonecrosis, and Osteomyelitis of the Ankle.
AB  - Advanced ankle arthritis, avascular osteonecrosis, and osteomyelitis of the ankle
      remain a surgical challenge in the foot and ankle arena with limited treatment
      options. Multiple medical comorbidities contribute to total loss of the talus.
      Collapse of the talar body as a complication of total ankle arthroplasty,
      talectomy in infection, and septic talus necrosis or severe bone defects caused
      by tumor resection may result in need for total talar replacement. Ankle
      arthrodesis and tibiocalcaneal fusion after talectomy can produce severe
      disability of the ankle and foot. Total ankle replacement is a viable option for
      treatment of end-stage ankle arthritis in appropriate patient populations.

PMID- 30223951
TI  - Treatment Strategies and Frame Configurations in the Management of Foot and Ankle
      Deformities.
AB  - To provide standardized nomenclature for various hexapod frame configurations for
      foot and ankle deformity correction, a unique classification of the hexapod
      external fixators was proposed. This classification is based on number of
      correction levels, secured anatomic blocks, and direction of the strut
      attachment. It allows the combination of all different foot and ankle frame
      assemblies into a few standard hexapod configurations, irrespective of which
      external fixator is used.

PMID- 30223952
TI  - Biomechanical Considerations in Foot and Ankle Circular External Fixation:
      Maintenance of Wire Tension.
AB  - Initial tensioning of the forefoot wires to 130 kg followed by simultaneous
      tensioning of the calcaneal wires to 90 kg and using the rigid double-row foot
      plate closed anteriorly via threaded rods produce maximum preservation of the
      initial wire tension during foot circular external fixation.

PMID- 30223953
TI  - Essentials of Deformity Planning.
AB  - Learning the essentials of deformity planning is the basis for the treatment of
      simple and complex deformities. Understanding the planes of deformity,
      radiographic correlation, and clinical correlations allows the surgeon to treat
      the condition with deeper knowledge of deformity, leading to improved deformity
      correction.

PMID- 30223954
TI  - Current Advancements in Ankle Arthrodiastasis.
AB  - Ankle arthrodiastasis offers an option for patients with end-stage primary or
      posttraumatic ankle osteoarthritis. The process allows for a joint salvage
      procedure as an alternative to arthrodesis or ankle implant arthroplasty. The
      distraction within the joint optimizes the intraarticular environment to permit
      equilibration of hydrostatic pressure, promoting subchondral morphoangiogenesis,
      and decreases subchondral sclerosis, thereby mitigating pain. This article
      highlights new advances and useful adjunctive procedures in this interesting
      approach to the management of ankle pain secondary to loss of functional joint
      surface.

PMID- 30223956
TI  - Lengthen, Alignment, and Beam Technique for Midfoot Charcot Neuroarthropathy.
AB  - Charcot neuroarthropathy is a disabling pathology in the foot and ankle. Midfoot
      Charcot is most common and results in progressive deformity. We describe a 2-step
      approach to surgical reconstruction, referred to as the lengthen, alignment, and
      beam technique. There is an initial surgery involving acute equinus correction
      through Achilles tendon lengthening and gradual correction with hexapod external
      fixation to align the deformity, followed by minimally invasive medial and
      lateral column beaming. This surgical protocol allows for adequate reduction of
      deformity. The second stage allows for rigid intramedullary fixation extending
      beyond the pathologic joints via a minimally invasive technique.

PMID- 30223955
TI  - The Gradual and Acute Correction of Equinus Using External Fixation.
AB  - Equinus is one of the most common deformities noted in foot and ankle
      biomechanics that, at times, if not identified and managed properly may lead to
      significant lower extremity pathology. With that being said, this deformity is
      also one that may be both underdiagnosed and undertreated. Treatment for equinus
      can range from conservative therapy to more aggressive surgical therapy. The
      purpose of this article is to review the clinical workup to properly identify the
      deformity and to explore the various treatment options for its timely management,
      which include gradual or acute correction of equinus using external fixation.

PMID- 30223957
TI  - Midfoot Charcot Reconstruction.
AB  - Midfoot Charcot joints are complex problems that are most commonly seen in
      patients with peripheral neuropathy secondary to diabetes. The goal of management
      is to prevent pedal collapse, which can lead to ulceration; infection; and in
      some cases, amputation. Principles of surgical management should be centered on
      respecting the soft tissue, obtaining correction, maintaining correction, and
      supplementing with orthobiologics to achieve healing. The authors present
      strategies, case examples, and tips and tricks to treat this complex condition
      with external and internal fixation.

PMID- 30223958
TI  - Innovations in Foot and Ankle Surgery.

PMID- 30223959
TI  - Back to the Future.

PMID- 30223960
TI  - Biology of Coagulation and Coagulopathy in Neurologic Surgery.
AB  - Hemostasis is a cell-based process that is regulated in a tissue-specific manner
      by the differential expression of procoagulant and anticoagulant factors on
      endothelial cells from different sites throughout the vasculature. The central
      nervous system, in particular, exhibits unique mechanisms of hemostatic
      regulation that favor increased activity of the tissue factor pathway. This
      results in an unusually high degree of protection against hemorrhage, at the
      potential expense of increased thrombotic risk. Unfortunately, standard
      laboratory assays, including the PT and aPTT, do not accurately reflect the
      complexity of hemostasis in vivo; therefore, they cannot predict the risk of
      bleeding or thrombosis.

PMID- 30223961
TI  - Evaluation of Coagulation in the Neurosurgery Patient.
AB  - Normal hemostasis provides for balanced interactions between the blood vessel
      wall, coagulation proteins, and platelets. After vascular injury, primary
      hemostasis and secondary hemostasis function in a coordinated fashion to stop
      bleeding. Standard coagulation tests have been shown in multiple studies to
      predict bleeding and mortality in neurosurgical patients. Emerging coagulation
      tests are useful point-of-care assays that guide transfusion therapy and diagnose
      patients with hyperfibrinolysis. This article provides an overview of hemostasis,
      a summary of standard coagulation testing and point-of-care tests, and a brief
      review of coagulation test usefulness in neurosurgery, focusing on studies in
      patients with traumatic brain injury.

PMID- 30223962
TI  - Genetics of Hypercoagulable and Hypocoagulable States.
AB  - Hemostasis is the normal process of blood coagulation in vivo to stop pathologic
      bleeding. Virchow triad includes venous stasis, hypercoagulability, and vascular
      injury. Natural anticoagulants include protein C, protein S, and antithrombin.
      Factor V Leiden is the most common inherited thrombophilia, followed by
      prothrombin gene mutation. All inherited thrombophilias are passed down in an
      autosomal dominant fashion. Patients harboring the antiphospholipid antibodies
      have an increased risk for thrombosis. von Willebrand disease is the most common
      inherited bleeding disorder; the pattern of inheritance is autosomal. Hemophilia
      A and B are the only hereditary bleeding disorders inherited in a sex-linked
      recessive pattern.

PMID- 30223963
TI  - Anticoagulants: Pharmacokinetics, Mechanisms of Action, and Indications.
AB  - Anticoagulant medications are used widely for a variety of medical and surgical
      diseases, disorders, and conditions associated with thrombosis and
      thromboembolism. This review highlights labeled indications, mechanisms of
      action, potential drug interactions, and specific pharmacokinetic characteristics
      of available anticoagulants as an essential foundation for guiding selection and
      management of therapies for patients undergoing neurosurgical procedures.

PMID- 30223964
TI  - Use of Antiplatelet Agents in the Neurosurgical Patient.
AB  - Antiplatelet agents used to treat neurovascular disease include aspirin; P2Y12
      receptor antagonists clopidogrel, prasugrel, and ticagrelor; ADP antagonist
      ticlopidine; phosphodiesterase inhibitor dipyridamole; and glycoprotein IIb/IIIa
      inhibitors abciximab, eptifibatide, and tirofiban. Numerous studies have been
      performed evaluating their efficacy in stroke, extracranial carotid artery
      disease and dissection, intracranial atherosclerotic disease, and moyamoya
      disease. The rapid technological advancements in endovascular neurosurgical
      devices have also made antiplatelet therapy a necessary part of treating
      intracranial aneurysms. This article presents the relevant data supporting the
      use of antiplatelet agents in vascular neurosurgery and recommendations based on
      the described studies.

PMID- 30223965
TI  - Common Conditions Requiring Long-Term Anticoagulation in Neurosurgical Patients.
AB  - Long-term anticoagulant therapy prevents thrombosis. Management of neurosurgical
      patients with conditions such as atrial fibrillation, mechanical heart valves,
      and other prothrombotic states necessitates application of a strategy to mitigate
      hemorrhagic complications of anticoagulation. Development of direct oral
      anticoagulants, which include the direct thrombin and factor X inhibitors, yields
      new considerations to be had, in particular, the introduction of reversal agents.
      This article reviews the more common chronic clinical entities that require the
      use of prolonged anticoagulant therapy with special consideration for
      neurosurgical patients. It also includes a discussion of established treatment
      strategies across available treatment options.

PMID- 30223966
TI  - Reversal of Systemic Anticoagulants and Antiplatelet Therapeutics.
AB  - Although antiplatelet medications and anticoagulants are necessary for numerous
      cardiac comorbidities, prevention of stroke, and treatment and prevention of
      venous thromboembolic events, they pose a significant treatment dilemma in
      neurosurgical patients, particularly in the setting of intracranial hemorrhage or
      prior to emergent neurosurgical procedures. For the majority of current
      anticoagulation and antiplatelet therapies, no direct reversal agents exist;
      however, there are numerous strategies that can be used to reverse or mitigate
      their antithrombotic properties. This review provides a comprehensive summary of
      the latest antiplatelet and anticoagulant therapies and the role of emergency
      reversal prior to emergent neurosurgical procedures.

PMID- 30223967
TI  - Intraoperative Blood and Coagulation Factor Replacement During Neurosurgery.
AB  - Intraoperative blood and coagulation factor transfusion is of particular
      importance to neurosurgeons. Maintaining the hematologic and coagulation
      parameters of the patient within normal limits during surgery is critical to
      facilitate normal hemostasis, reduce transfusion requirements, and prevent
      complications associated with excessive blood loss. In this article, the authors
      review topics relevant to intraoperative transfusion during neurosurgery,
      including laboratory studies and other diagnostic modalities available to help
      with decision making, blood components and coagulation factors currently
      available for transfusion, and indications for intraoperative transfusion during
      cranial and spinal neurosurgical procedures.

PMID- 30223968
TI  - Management of Intraoperative Coagulopathy.
AB  - Intraoperative bleeding can be minimized with optimal preoperative preparation
      but cannot be completely prevented. There are circumstances when patients need
      emergent operative intervention, and thorough hemostatic evaluation and
      preparation is not possible. In this review, the authors summarize the
      recommendations for rapid reversal of vitamin K antagonists and direct oral
      anticoagulants before procedures. The authors review the potential causes for
      intraoperative bleeding and the methods for rapid and accurate diagnosis. The
      authors summarize the current evidence for treatment options, including
      transfusion of platelets and coagulation factors and the use of topical agents,
      antidotes to direct-acting anticoagulants, antifibrinolytics, and desmopressin.

PMID- 30223969
TI  - Deep Vein Thrombosis Prophylaxis in the Neurosurgical Patient.
AB  - The optimal approach for deep vein thrombosis (DVT) prophylaxis in the
      neurosurgery patient is a challenge of balancing the reduction in incidence of
      DVT and pulmonary embolus (PE) without risking an increase in catastrophic
      hemorrhages. In this article, the authors review the current literature on DVT/PE
      prophylaxis in neurosurgery. Mechanical and pharmacologic DVT prophylaxis
      strategies are discussed in terms of their efficacy in reducing DVT/PE rates as
      well as safety in terms of catastrophic hemorrhages. The authors offer
      recommendations regarding the best approach given the current state of the
      literature.

PMID- 30223970
TI  - Postoperative Anticoagulation After Neurologic Surgery.
AB  - Management of anticoagulation and antiplatelet medications after neurosurgery can
      be complex, especially given that these patients have multiple medical
      comorbidities. In turn, neurosurgical patients are at high risk for the
      development of venous thromboembolism after surgery, so neurosurgeons must
      consider the use of pharmacologic prophylaxis. Developments in endovascular
      neurosurgery have produced therapies that require close management of
      antiplatelet medications to prevent postoperative complications. Any of these
      patient populations may need intrathecal access. This article highlights current
      strategies for managing these issues in the neurosurgical patient population.

PMID- 30223971
TI  - Management of Venous Sinus Thrombosis.
AB  - Cerebral venous sinus thrombosis (CVST) is a rare subtype of cerebrovascular
      disease representing 0.5% of strokes. The signs and symptoms of CVST are often
      nonspecific, and variable in duration, with the common results being delayed
      diagnosis and treatment. Increased awareness in the medical community and
      advancements in imaging modalities have produced faster diagnosis with improved
      patient outcomes. The preferred initial treatment is with a low molecular weight
      heparin. After the acute stage of CVST, treatment with a vitamin K antagonist
      (oral anticoagulant therapy) is recommended. Current evidence suggests that in
      the future, factor Xa inhibitor drugs may be used for long-term therapy.

PMID- 30223972
TI  - Management of Acute Ischemic Thrombosis.
AB  - Acute ischemic thrombosis in patients who have undergone neurosurgical procedures
      is a leading cause of mortality and long-term disability. Endovascular therapy
      has become an important treatment modality for acute ischemic thrombosis in these
      patients. Noninvasive imaging has dramatically changed the understanding of
      cerebral blood flow and the concepts of cerebrovascular reserve and salvageable
      penumbra. Increasingly, reliance on perfusion imaging to discern tissue viability
      and potential outcomes has become standard of care. With the advent of recent
      acute ischemic stroke trials, therapy for occlusive cerebrovascular disease is
      evolving, and understanding when to intervene is becoming paramount.

PMID- 30223973
TI  - Management of Intracranial Hemorrhage in the Anticoagulated Patient.
AB  - Antiplatelet and anticoagulant drugs (antithrombotic drugs) can cause or be
      associated with intracranial hemorrhage. Patients who take antithrombotic drugs
      are at higher risk for intracranial hemorrhage after trauma and are
      neurologically worse acutely compared with patients not on antithrombotic drugs.
      Treatment of patients on antithrombotic drugs who have intracranial hemorrhage
      includes reversal of anticoagulant drugs in almost all cases. This article is a
      synopsis of the data pertaining to intracranial hemorrhage and antithrombotic
      drugs and methods to diagnose the pharmacologic effects and to reverse the
      effects of these drugs in patients with traumatic or spontaneous intracranial
      hemorrhage.

PMID- 30223974
TI  - Coagulation and Hematology in Neurologic Surgery.

PMID- 30223975
TI  - A new era for tuberculosis?

PMID- 30223976
TI  - Missing in the middle: measuring a million deaths annually in children aged 5-14
      years.

PMID- 30223977
TI  - Safe mass drug administration for neglected tropical diseases.

PMID- 30223978
TI  - Typhoid fever outbreak with severe complications in Yucatan, Mexico.

PMID- 30223979
TI  - Tuberculosis control: recalling past insights.

PMID- 30223980
TI  - Presbyopia and the Sustainable Development Goals.

PMID- 30223981
TI  - Neglected risk factors of childhood morbidity and mortality caused by
      Cryptosporidium infection.

PMID- 30223982
TI  - Essentials of Global Health: a book for students, by students.

PMID- 30223983
TI  - The fifth most prevalent disease is being neglected by public health
      organisations.

PMID- 30223984
TI  - Global, regional, and national mortality trends in older children and young
      adolescents (5-14 years) from 1990 to 2016: an analysis of empirical data.
AB  - BACKGROUND: From 1990 to 2016, the mortality of children younger than 5 years
      decreased by more than half, and there are plentiful data regarding mortality in
      this age group through which we can track global progress in reducing the under-5
      mortality rate. By contrast, little is known on how the mortality risk among
      older children (5-9 years) and young adolescents (10-14 years) has changed in
      this time. We aimed to estimate levels and trends in mortality of children aged 5
      14 years in 195 countries from 1990 to 2016. METHODS: In this analysis of
      empirical data, we expanded the United Nations Inter-agency Group for Child
      Mortality Estimation database containing data on children younger than 5 years
      with 5530 data points regarding children aged 5-14 years. Mortality rates from
      1990 to 2016 were obtained from nationally representative birth histories, data
      on household deaths reported in population censuses, and nationwide systems of
      civil registration and vital statistics. These data were used in a Bayesian B
      spline bias-reduction model to generate smoothed trends with 90% uncertainty
      intervals, to determine the probability of a child aged 5 years dying before
      reaching age 15 years. FINDINGS: Globally, the probability of a child dying
      between the ages 5 years and 15 years was 7.5 deaths (90% uncertainty interval
      7.2-8.3) per 1000 children in 2016, which was less than a fifth of the risk of
      dying between birth and age 5 years, which was 41 deaths (39-44) per 1000
      children. The mortality risk in children aged 5-14 years decreased by 51% (46-54)
      between 1990 and 2016, despite not being specifically targeted by health
      interventions. The annual number of deaths in this age group decreased from 1.7
      million (1.7 million-1.8 million) to 1 million (0.9 million-1.1 million) in 1990
      2016. In 1990-2000, mortality rates in children aged 5-14 years decreased faster
      than among children aged 0-4 years. However, since 2000, mortality rates in
      children younger than 5 years have decreased faster than mortality rates in
      children aged 5-14 years. The annual rate of reduction in mortality among
      children younger than 5 years has been 4.0% (3.6-4.3) since 2000, versus 2.7%
      (2.3-3.0) in children aged 5-14 years. Older children and young adolescents in
      sub-Saharan Africa are disproportionately more likely to die than those in other
      regions; 55% (51-58) of deaths of children of this age occur in sub-Saharan
      Africa, despite having only 21% of the global population of children aged 5-14
      years. In 2016, 98% (98-99) of all deaths of children aged 5-14 years occurred in
      low-income and middle-income countries, and seven countries alone accounted for
      more than half of the total number of deaths of these children. INTERPRETATION:
      Increased efforts are required to accelerate reductions in mortality among older
      children and to ensure that they benefit from health policies and interventions
      as much as younger children. FUNDING: UN Children's Fund, Bill & Melinda Gates
      Foundation, United States Agency for International Development.

PMID- 30223985
TI  - Feasibility and safety of mass drug coadministration with azithromycin and
      ivermectin for the control of neglected tropical diseases: a single-arm
      intervention trial.
AB  - BACKGROUND: Mass drug administration has made a major contribution to the public
      health control of several important neglected tropical diseases. For settings
      with more than one endemic disease, combined mass drug administration has
      potential practical advantages compared with separate programmes but needs
      confirmation of feasibility and safety. We undertook a study of mass drug
      administration in the Solomon Islands for trachoma and scabies control using
      ivermectin and azithromycin, key drugs in the control of neglected tropical
      diseases worldwide. METHODS: The entire population of Choiseul province, Solomon
      Islands, was eligible to participate. An azithromycin-based mass drug
      administration regimen was offered in line with standard recommendations for
      trachoma elimination (oral azithromycin or topical tetracycline). An ivermectin
      based mass drug administration regimen was offered at the same time (oral
      ivermectin or topical permethrin), with a further dose 7-14 days later, using a
      modified version of a regimen demonstrated to be effective for scabies control.
      All participants underwent safety assessments 7-14 days later. Participants in
      ten randomly selected sentinel villages underwent a more detailed safety
      assessment. Routine health system reports of hospital or clinic admissions and
      deaths were also obtained to compare health outcomes in the 12 month period
      before and after the mass drug administration. FINDINGS: The study enrolled 26
      188 participants, 99.3% of the estimated resident population as determined at the
      2009 census. Of those enrolled, 25 717 (98.2%) received the trachoma regimen and
      25 819 (98.6%) received the first dose of the scabies regimen between Sept 1, and
      Oct 2, 2015. A second dose of the scabies regimen was received by 21 931 (83.7%)
      of participants. Adverse events, all mild and transient, were recorded in 571
      (2.6%) of the entire study population and 58 (4.1%) of participants in the ten
      sentinel villages. In the 12 months before and after the mass drug administration
      the numbers of hospital admissions (1530 vs 1602) and deaths (73 vs 83) were
      similar. In the month after the mass drug administration, 84 individuals were
      admitted to hospital and two died, compared with a monthly median of 116
      admissions (IQR 106-159) and six deaths (IQR 4-7) in the 12 months before and
      after the mass drug administration. INTERPRETATION: In the largest trial so far
      involving coadministration of regimens based on ivermectin and azithromycin, the
      combination was safe and feasible in a population of more than 26 000 people.
      Coadministration of mass drug administration based on these two drugs opens up
      new potential for the control of neglected tropical diseases. FUNDING:
      International Trachoma Initiative, Murdoch Children's Research Institute, Scobie
      and Claire Mackinnon Trust, Wellcome Trust.

PMID- 30223986
TI  - Evidence for Clinical Anaplasmosis and Borreliosis in Cats in Maine.
AB  - The objectives of this study were to use data from client-owned cats in an Ixodes
      scapularis endemic area to evaluate for clinical associations with diagnostic
      test results for Anaplasma phagocytophilum and Borrelia burgdorferi and to
      provide information from a group of cats with possible borreliosis as the cause
      of clinical manifestations of disease. All cases were evaluated at one clinic,
      medical records were evaluated, and sera from all cats were tested using one of
      two commercially available assays labeled for the use with dog sera (SNAP 4Dx or
      SNAP 4Dx Plus; IDEXX Laboratories, Westbrook, ME). Of the 159 cats evaluated, 42
      cats (26.4%) had clinical signs consistent with A. phagocytophilum or B.
      burgdorferi infection and 117 cats (73.6%) were apparently healthy. Antibodies
      against B. burgdorferi or A. phagocytophilum were detected in sera of 18.2% and
      6.3% of the 159 cats, respectively. Cats with clinical signs of disease were 4
      times more likely to have antibodies against one or both agents than healthy cats
      (95% confidence interval [CI] 1.7928-8.9246; P = .0007), cats allowed outdoors
      were 5 times more likely to have antibodies against one or both agents than cats
      housed exclusively indoors (95% CI 2.0196-12.4497; P = .0005), and cats of owners
      who purchased acaricides were more likely (odds ratio = .3977) to have antibodies
      against one or both agents than cats of owners who did not purchase acaricides
      (95% CI .1659-.9534; P = .0387). The cats in the case series were believed to
      have B. burgdorferi infection as the most likely cause of illness based on
      serological testing, select clinical information, and apparent response to
      administration of doxycycline. The results suggest that both A. phagocytophilum
      and B. burgdorferi are associated with clinical illness in cats. Owners of cats
      allowed outdoors should be diligent in the use of acaricides.

PMID- 30223988
TI  - Read All About It: Health Literacy and Veterinary Client Educational Materials.

PMID- 30223989
TI  - Patient and Population-Level Approaches to Persistent Critical Illness and
      Prolonged Intensive Care Unit Stays.
AB  - The differential diagnosis of prolonged intensive care unit (ICU) stays includes
      intrinsic patient and admitting diagnostic characteristics, occurrences during
      the course of critical illness, and system failures. Existing data suggest that
      the most common cause of prolonged ICU stay is the development of new cascading
      problems, which is now more related to ongoing critical illness than the original
      reason for ICU admission. Accepting the dynamism inherent in such a clinical
      course has implications for contemporary clinical care.

PMID- 30223987
TI  - Feline Herpesvirus 1 and Mycoplasma spp. Conventional PCR Assay Results From
      Conjunctival Samples From Cats in Shelters With Suspected Acute Ocular
      Infections.
AB  - Signs of ocular infections like discharge and conjunctivitis occur commonly in
      cats in shelters and feline herpesvirus 1 (FHV-1), Chlamydia felis, Mycoplasma
      spp, and feline calicivirus (FCV) are thought to be the most common causes. While
      molecular assays are available to amplify nucleic acids of each of these agents
      as single tests or in panels, additional information is needed concerning whether
      the assay results can be used to predict response to treatment. The objectives of
      this study were to report results for conventional polymerase chain reaction
      (PCR) assays that amplify nucleic acids of FHV-1, Mycoplasma spp., C. felis, and
      FCV from cats with signs of acute ocular and upper respiratory infections in an
      animal shelter and to determine whether the results are associated with treatment
      responses to topical administration of cidofovir (anti-FHV-1) or oxytetracycline
      (anti-Mycoplasma spp. and C. felis). Conjunctival samples were collected from
      both eyes of 60 cats with ocular signs of disease. Total deoxyribonucleic acid
      (DNA) and ribonucleic acid (RNA) were extracted from each sample and assayed for
      DNA of FHV-1, Mycoplasma spp., and C. felis and RNA of FCV by conventional PCR
      assays. Cats were randomized to be administered either oxytetracycline ointment
      or cidofovir drops in both eyes and a standardized ocular disease score system
      was used to determine a total ocular score for each cat prior to treatment on Day
      0 and on Day 7. Nucleic acids of one or more agents were amplified from one or
      both eyes from 39 of 60 cats (65%). FHV-1 DNA (21 cats), Mycoplasma spp. DNA (25
      cats) or FCV RNA (2 cats) were amplified most commonly. After treatment for 7
      days, 32 of 60 cats (53.3%) were considered improved with 27 of 32 cats (84.4%)
      having ocular scores of 0 (21 cats) or 1 (6 cats). When the results of the FHV-1
      PCR assay were compared to cidofovir treatment responses, the positive and
      negative predictive values of the assay were shown to be 29.4% and 60%,
      respectively. When the results of the Mycoplasma spp. PCR assay were compared to
      oxytetracycline treatment responses, the positive and negative predictive values
      of the assay were shown to be 40% and 38.5%, respectively. The predictive value
      of conventional PCR assay results for FHV-1 or Mycoplasma spp. DNA was low,
      suggesting that performing these tests to formulate a treatment protocol has
      minimal clinical utility in cats with suspected acute ocular infections.

PMID- 30223990
TI  - Preventing Chronic Critical Illness and Rehospitalization: A Focus on Sepsis.
AB  - An estimated 14 million patients survive sepsis hospitalization each year.
      However, survivors commonly experience new functional disability, cognitive
      impairment, and a high rate of further medical setbacks, including hospital
      readmission and late death. One in 5 older survivors has a potentially
      preventable hospital admission with in 90 days, most commonly for infection.
      Treatment should focus on preventing the common sequelae of critical illness
      during the initial hospitalization, tailoring medical care to minimize the risk
      for common and potentially preventable causes of hospital readmission, and
      promoting functional recovery.

PMID- 30223991
TI  - Measuring Outcomes After Critical Illness.
AB  - Outcomes after critical illness remain poorly understood. Conceptual models
      developed by other disciplines can serve as a framework by which to increase
      knowledge about outcomes after critical illness. This article reviews 3 models to
      understand the distinct but interrelated content of outcome domains, to review
      the components of functional status, and to describe how injuries and illnesses
      relate to disabilities and impairments afterward.

PMID- 30223992
TI  - Frailty and the Association Between Long-Term Recovery After Intensive Care Unit
      Admission.
AB  - Frailty is common, although infrequently screened for among patients admitted to
      intensive care. Frailty has been the focus of research in geriatric medicine;
      however, its epidemiology and interaction with critical illness have only
      recently been studied. Instruments to screen for and measure frailty require
      refinement in intensive care settings. Frail critically ill patients are at
      higher risk of poor outcomes. Frail survivors of critical illness are high users
      of health resources. Further research is needed to understand how frailty
      assessment can inform decision-making before and during an episode of critical
      illness and during an intensive care course for frail patients.

PMID- 30223993
TI  - The Pathophysiology of Neuromuscular Dysfunction in Critical Illness.
AB  - Disability after critical illness is heterogeneous and related to multiple
      morbidities. Muscle and nerve injury represent prevalent and important
      determinants of long-term disability. As the population ages and accrues a
      greater burden of comorbid illness and medical complexity, those patients
      admitted to an intensive care unit will be challenged in their recovery because
      of diminished organ reserve and variable tissue resiliency. This represents a
      significant burgeoning public health concern. This article presents a brief
      overview of the pathophysiology and the emerging basic science of neuromuscular
      dysfunction in critical illness.

PMID- 30223994
TI  - Early Mobilization in the Intensive Care Unit to Improve Long-Term Recovery.
AB  - This article outlines the effect of early mobilization on the long-term recovery
      of patients following critical illness. It investigates the safety of performing
      exercise in this environment, the differing types of rehabilitation that can be
      provided, and the gaps remaining in evidence around this area. It also attempts
      to assist clinicians in prescription of exercise in this cohort while informing
      all readers about the impact that mobilization can have for the outcomes of
      intensive care patients.

PMID- 30223995
TI  - Intensive Care Nutrition and Post-Intensive Care Recovery.
AB  - Intensive care unit (ICU)-acquired weakness frequently complicates critical
      illness, which prolongs intensive care dependency and causes long-term burden.
      Observational studies have suggested that prolonged underfeeding could aggravate
      ICU-acquired weakness and impair outcome. However, recent large randomized
      controlled trials have failed to show a benefit of early enhanced nutrition to
      critically ill patients. Moreover, early parenteral nutrition was even shown to
      increase ICU-acquired weakness and prolong organ failure and intensive care
      dependency, which may be explained by feeding-induced suppression of autophagy.
      Currently, the ideal timing of artificial nutrition for critically ill patients
      as well as the optimal dose and composition remain unclear.

PMID- 30223996
TI  - Sedation, Delirium, and Cognitive Function After Critical Illness.
AB  - Delirium has been consistently identified as a risk factor for critical illness
      brain injury, but ICU patients are exposed to a multitude of risk factors for
      delirium and it remains unclear which of these risk factors should be targeted to
      improve long-term cognitive outcomes. Because exposure to sedating medications
      which are frequently used to treat unwanted yet common symptoms during critical
      illness-is a risk factor for delirium that is directly controlled by clinicians,
      the relationship between sedation, delirium, and long-term cognition is of great
      interest to clinicians, researchers, and patients. This review describes
      theoretic relationships between sedation, delirium, and long-term cognition and
      reviews the evidence supporting these theoretic relationships.

PMID- 30223997
TI  - Psychiatric Morbidity After Critical Illness.
AB  - Critical illness survivors frequently have substantial psychiatric morbidity,
      including posttraumatic stress, depression, and anxiety symptoms. Prior
      psychiatric illness is a potent predictor of postcritical illness psychiatric
      morbidity. Early emotional distress and memories of frightening psychotic and
      nightmarish intensive care unit (ICU) experiences are risk factors for longer
      term psychiatric morbidity. ICU diaries may be effective in decreasing
      psychiatric morbidity after critical illness, though these and other
      interventions deserve further study.

PMID- 30223999
TI  - Preface: Complications During and After Critical Illness.

PMID- 30223998
TI  - Family and Support Networks Following Critical Illness.
AB  - Research highlights the psychosocial impact of critical illness on family who
      typically adopt a caregiver role to the survivor. We review evidence on informal
      caregiver psychosocial outcomes and interventional studies designed to improve
      them. We argue informal caregivers have distinct and complex needs that differ
      from patients. Interventional studies ought to be designed for this cohort with
      careful attention paid to the timing of interventions. We consider the influence
      of social isolation on recovery and discuss service improvement approaches to
      build social support networks to enhance recovery, where caregivers and survivors
      are involved in the design of aftercare programs.

PMID- 30224000
TI  - The Role of Patient Education in Arthritis Management: The Utility of Technology.
AB  - Technologies continue to shape the path of medical treatment. Orthopedic surgeons
      benefit from becoming more aware of how twenty-first century information
      technology (IT) can benefit patients. The percentage of orthopedic patients
      utilizing IT resources is increasing, and new IT tools are becoming utilized.
      These include disease-specific applications. This article highlights the
      opportunity for developing IT tools applicable to the growing population of
      patients with osteoarthritis (OA), and presents a potential solution that can
      facilitate the way OA education and treatment are delivered, and thereby maximize
      efficiency for the health care system, the physician, and the patient.

PMID- 30224001
TI  - Improving Total Joint Replacement with Continuous Quality Improvement Methods and
      Tools.
AB  - Faced with increasing pressure to reduce costs, hospitals must find new ways to
      eliminate waste while simultaneously maintaining the highest quality of care. For
      any institution, these can types of changes can be complex and burdensome. This
      article outlines several methods that have been successful in reducing costs
      while maintaining high quality and highlights feasible methodologies that can
      help health care providers implement new quality improvement protocols.

PMID- 30224002
TI  - Professional Formation of Physicians Focused on Improving Care: How Do We Get
      There?
AB  - As the Accreditation Council for Graduate Medical Education (ACGME) and National
      Academy of Medicine (NAM) increase emphasis on quality improvement (QI),
      continuing medical education must also adapt to meet these increasing demands. In
      fellowship programs and for attending physicians, QI initiatives exist but are
      more rare compared with initiatives during residency programs, and they are even
      more rare for orthopedic surgery residents, fellows, and attending physicians. A
      QI curriculum should be in place at all stages of continuing medical education,
      as they help meet the criteria of the ACGME and NAM and promote better clinical
      practice and minimize errors.

PMID- 30224003
TI  - Walk a Mile in the Leadership's Shoes: Why Focus on Quality Improvement?
AB  - Quality Improvement (QI) throughout health care in the United States continues to
      be of growing importance to both patients and providers. Leaders in health care
      including physicians, nurses, hospital administrators, and payors are all
      responsible for ensuring the continuation and growth of QI initiatives. This
      article will discuss various ways that healthcare leaders, with specific regard
      to orthopedic surgery, have utilized QI measures to provide better, more
      efficient, care to patients.

PMID- 30224005
TI  - The Role of Value-Based Implants in Orthopedic Trauma.
AB  - Health care costs in the United States continue to rise, and economic pressures
      influencing the care of the orthopedic trauma patient have never been greater.
      Value-based health care is vital to the survival of the current health care
      system, and the use of value-based implants is central to success. Value-based
      implants have similar clinical outcomes to conventional implants; however,
      multiple barriers exist. Despite biomechanical equivalence and significant cost
      savings, surgeons have difficultly changing implant use without financial
      incentive. The rise of physician-owned surgery centers, bundled payments, and
      gain sharing and comanagement agreements will likely drive this change.

PMID- 30224004
TI  - Osteolysis as it Pertains to Total Hip Arthroplasty.
AB  - Osteolysis is a long-term complication of total hip arthroplasty (THA). As the
      projected number of THAs performed annually increases, osteolysis will likely
      continue to occur. However, because of advancements in prosthesis design,
      metallurgy, and enhanced bearing surfaces, fewer revision THAs will be linked to
      osteolysis and aseptic loosening. Despite these improvements, no preventative
      therapies are currently available for the management of osteolysis other than
      removing and replacing the source of bearing wear.

PMID- 30224006
TI  - The Role of Business Education in the Orthopedic Curriculum.
AB  - The field of orthopedics is becoming increasingly complex as the demands for
      success are not merely clinical competence and good interpersonal skills. To
      achieve practice stability strategic planning, contract negotiation, health care
      law, practice management, health care economics, and personal finance are all
      needed skills. Unfortunately, most of these areas of professional growth require
      some basic background in business principles. This is an area that most recent
      residency graduates feel is neglected as a core educational competency. In these
      changing times, it is imperative that orthopedic residents and fellows obtain
      some formal business education.

PMID- 30224007
TI  - MRI Safety with Orthopedic Implants.
AB  - The literature within the last 10 years on MRI use in patients with orthopedic
      implants is reviewed. A literature search returned 15 relevant articles. Only 2
      discussed pediatric patients. Overall, significant displacement of implants was
      infrequent. Radiofrequency-induced heating of implants differed among the
      studies, but most reported increases of less than 1 degrees C. The authors
      conclude MRI is safe in patients with orthopedic implants because implant
      displacement and heating pose little risk to patients. A risk-to-benefit ratio is
      warranted, however, to assess the clinical utility and necessity of the study.
      Further research and individual assessment of implant properties and MRI-related
      interactions are warranted.

PMID- 30224008
TI  - Perioperative Safety: Keeping Our Children Safe in the Operating Room.
AB  - The entire operating room team is responsible for the safety of children in the
      operating room. As a leader in the operating room, the surgeon is impactful in
      ensuring that all team members are committed to providing this safe environment.
      This is achieved by the use of perioperative huddles or briefings, the use of
      appropriate surgical checklists, operating room standardization, surgeons
      proficient in the care they provide, and team members that embrace Just Culture.

PMID- 30224010
TI  - Quality, Safety, and Value in Pediatric Spine Surgery.
AB  - The article addresses patient safety topics in spine surgery, including
      infection, length of stay, instrumentation strategies, pedicle screw malposition,
      radiation exposure, and neurologic events. Quality, safety, and value are
      concepts that are practical, easy to understand, and can be implemented on any
      scale and may be matched to individual practices. Further, with quality
      improvement, there is a culture shift to openly share information, protocols, and
      strategies so that more patients can rapidly benefit.

PMID- 30224009
TI  - Standardization of Care of Common Pediatric Fractures.
AB  - Distal radius fractures are the most common site of fracture in the pediatric
      population. Supracondylar humerus fractures are the most common pediatric elbow
      fracture. Although there is abundant literature discussing treatment and outcomes
      of these fractures, there is only emerging literature specifically discussing the
      variation in care among surgeons. There is need for standardization of these
      types of injuries to optimize the quality, safety, and value for patients.
      Quality improvement methodology differs from traditional research and is meant to
      be shared and used to implement changes quickly. This article discusses basic
      quality improvement methodology.

PMID- 30224011
TI  - Cost, Value, and Patient Satisfaction in Carpal Tunnel Surgery.
AB  - The cost of carpal tunnel release (CTR) surgery can be decreased and patient
      satisfaction increased by a few relatively simple changes. Although cost
      estimates vary in the literature, most investigators agree that open CTR costs
      less than endoscopic CTR, and the clinic procedure room or ambulatory surgery
      center is cheaper than the ambulatory surgery center, which is less than the
      hospital. Patient satisfaction can be increased by making office visits more
      patient-centered and improving the quality of dialogue between the surgeon and
      patient.

PMID- 30224012
TI  - Practicing Cost-Conscious Shoulder Surgery.
AB  - Second only to the knee, the shoulder is the most commonly reported area of
      chronic joint pain. By practicing evidence-based methods for improved outcomes at
      lower costs, providers can increase both efficiency and margin, while patients
      experience better care and higher satisfaction. Current cost studies on shoulder
      care provide a base for improving evidence-based care and improving value.

PMID- 30224013
TI  - The Volume-Value Relationship in Shoulder Arthroplasty.
AB  - Improving value in shoulder arthroplasty has gained increasing importance as
      procedure volume increases. To enhance the value of shoulder arthroplasty, an
      improvement of outcomes or a decrease in associated costs must occur. With the
      recent shift to a value-based care delivery model, analysis of the effects of
      surgical volume presents an opportunity to improve outcomes and reduce costs in
      shoulder arthroplasty. There are multiple reports in the literature expanding on
      the relationship between increased surgeon and hospital procedure volume and
      increased value for shoulder arthroplasty, by way of improved outcomes or
      decreased cost. This article highlights these studies.

PMID- 30224014
TI  - Patient Safety: Driving After Foot and Ankle Surgery.
AB  - This article provides a review of the existing literature regarding driving
      limitations following lower extremity orthopedic surgery. Medicolegal
      requirements and insurance recommendations are often vague and subject to
      interpretation. Several studies have examined the impact of surgery and
      immobilization on brake reaction time. This study summarizes the findings of
      these studies. Additionally, the authors consider the impact of lower extremity
      amputations and peripheral vascular disease on driving. Literature regarding
      opioid use, obesity, sleep apnea, increasing age, and distraction is also
      reviewed. An improved understanding of these topics will enhance the orthopedic
      surgeon's ability to counsel patients and optimize their safety.

PMID- 30224015
TI  - Optimizing Outpatient Total Ankle Replacement from Clinic to Pain Management.
AB  - Outpatient total ankle arthroplasty is a potential significant source of cost
      savings. The ability to institute an effective outpatient total ankle program
      depends on appropriate patient selection, surgeon experience with total ankle
      replacement, addressing preoperative patient expectations, the involvement of an
      experienced multidisciplinary care team including experienced anesthesiologists,
      nurse navigators, recovery room nursing staff and physical therapists, and most
      importantly, such a program requires complete institutional logistical support.

PMID- 30224016
TI  - Quality, Value, and Patient Safety in Orthopedic Surgery.

PMID- 30224017
TI  - Rapamycin Supplementation May Ameliorate Erectile Function in Rats With
      Streptozotocin-Induced Type 1 Diabetes by Inducing Autophagy and Inhibiting
      Apoptosis, Endothelial Dysfunction, and Corporal Fibrosis.
AB  - INTRODUCTION: Erectile dysfunction (ED), which is common in patients with
      diabetes mellitus (DM), seriously affects quality of life. Previous studies on
      the treatment of DM-induced ED (DMED) involve autophagy, but the specific effect
      and mechanism of treatment are not yet clear. AIM: To investigate the effect and
      mechanism of rapamycin, an autophagy inducer, in ameliorating DMED. METHODS: 45
      male Sprague-Dawley rats (7 weeks old) were used in the experiment. 8 rats were
      randomly selected as the control group; the other rats were treated with
      streptozotocin to induce type 1 DM. After 10 weeks, an apomorphine test was used
      to confirm DMED. Rats with DMED were intraperitoneally injected with rapamycin or
      vehicle for 3 weeks. Rats in the control group were injected with saline.
      Erectile function in rats was measured by electrically stimulating the cavernous
      nerve. The penises were then harvested for histologic examinations, ribonucleic
      acid (RNA), and protein levels of related factors by immunohistochemistry,
      immunofluorescence, real-time polymerase chain reaction, enzyme-linked
      immunosorbent assay, and Western blot. MAIN OUTCOME MEASURE: Erectile function
      was evaluated by maximum intracavernous pressure and mean arterial pressure.
      Penile tissues were used to perform histologic examinations and to determine the
      RNA and protein levels. RESULTS: Erectile function, which was impaired in rats
      with DMED, was significantly ameliorated in the DMED + rapamycin group. The
      nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway was inhibited in
      the DMED group, and rapamycin significantly reduced this inhibition. The DMED
      group showed increased autophagy and apoptosis level compared with the non
      diabetic group, and rapamycin increased the autophagy level and decreased the
      apoptosis level in the penis. Penile fibrosis was more severe in the DMED group
      than in the control group and was partially but significantly improved in the
      DMED + rapamycin group compared with the DMED group. The adenosine monophosphate
      activated protein kinase (AMPK)/mammalian target of rapamycin kinase (mTOR) and
      PI3K/AKT/mTOR pathways were activated, and the mTOR (regulatory associated
      protein of mTOR, complex 1 [raptor])/p70 ribosomal protein S6 kinase (p70S6K)
      pathway was inhibited in the DMED group. Compared with DMED group, rapamycin led
      to lower AMPK/mTOR and AKT/mTOR pathways expression, a higher degree of mTOR
      (raptor)/p70S6K pathway inhibition, and no change in the mTORC2-related pathway.
      CLINICAL IMPLICATIONS: Rapamycin was effective in restoring erectile function in
      type 1 DMED models. STRENGTH AND LIMITATIONS: This study suggested for the first
      time that rapamycin, an autophagy inducer, is effective in restoring erectile
      function in rats with diabetes. However, the rat model might not represent the
      human condition. CONCLUSION: Rapamycin improved erectile function in rats with
      DMED, likely by promoting autophagy, inhibiting apoptosis and fibrotic activity,
      and ameliorating endothelial function. These findings provide evidence of a
      potential treatment option for DMED. Lin H, Wang T, Ruan Y, et al. Rapamycin
      supplementation may ameliorate erectile function in rats with streptozotocin
      induced type 1 diabetes by inducing autophagy and inhibiting apoptosis,
      endothelial dysfunction, and corporal fibrosis. J Sex Med 2018;15:1246-1259.

PMID- 30224018
TI  - Abnormal White Matter Microstructure in Lifelong Premature Ejaculation Patients
      Identified by Tract-Based Spatial Statistical Analysis.
AB  - INTRODUCTION: Several recent neuroimaging studies have identified functional and
      structural abnormalities in the cerebral cortex of lifelong premature ejaculation
      (LPE) patients, including task-related and resting-state brain function, and
      cortical thickness, although changes in white matter microstructure have not been
      reported. AIM: To assess the differences in white matter microstructure between
      LPE patients and healthy controls. METHODS: Diffusion tensor imaging (DTI) and
      tract-based spatial statistical analysis were used to detect differences in white
      matter microstructure between 32 LPE patients and 32 matched healthy controls. We
      also analyzed correlations of clinical indices with significant DTI-based
      features. MAIN OUTCOME MEASURES: DTI-based features (including fractional
      anisotropy [FA], mean diffusivity, axial diffusivity, and radial diffusivity)
      were assessed in LPE patients and controls, as well as the correlation of white
      matter changes in LPE patients with clinical data (including the premature
      ejaculation diagnostic tool score and the International Index of Erectile
      Function). RESULTS: LPE patients showed widespread increases in FA and axial
      diffusivity values compared with controls, including in the right posterior
      thalamic radiation, posterior corona radiata, bilateral posterior limb of the
      internal capsule, superior corona radiata, and external capsule. Further, FA in
      the right posterior thalamic radiation was positively correlated with the
      premature ejaculation diagnostic tool score in LPE patients. CLINICAL
      IMPLICATIONS: Changes of white matter microstructure may be an underlying marker
      for evaluating sensory conduction efficiency in LPE patients. STRENGTHS &
      LIMITATIONS: There are no previous studies examining white matter microstructure
      in LPE patients. The present study furthers our understanding of the etiology of
      LPE. Limitations include a cross-sectional study design without causal
      information, and no measurement of conduction efficiencies such as cortical
      somatosensory-evoked potential from the penis, or psychosocial factors.
      CONCLUSION: Our findings show potential microstructural white matter
      abnormalities related to LPE, suggesting that changes in fiber pathways
      connecting the cerebral cortex and the thalamus may play roles in the etiology of
      LPE. Gao M, Yang X, Liu L, et al. Abnormal White Matter Microstructure in
      Lifelong Premature Ejaculation Patients Identified by Tract-Based Spatial
      Statistical Analysis. J Sex Med 2018;15:1272-1279.

PMID- 30224019
TI  - A Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Utility of
      Tacrolimus (FK506) for the Prevention of Erectile Dysfunction Following Bilateral
      Nerve-Sparing Radical Prostatectomy.
AB  - INTRODUCTION: Radical prostatectomy (RP) is associated with erectile dysfunction,
      largely mediated through cavernous nerve injury. There are robust pre-clinical
      data supporting a potential role for neuromodulatory agents in this patient
      population. This study assessed tacrolimus in improving erectile function
      recovery rates after RP (ClinicalTrials.gov number, NCT00106392). AIM: To define
      the utility of oral tacrolimus in improving erectile function recovery after
      nerve sparing radical prostatectomy. METHODS: A randomized, double-blind trial
      compared tacrolimus 2-3 mg daily and placebo in men undergoing RP. Patients had
      localized prostate cancer and excellent baseline erectile function, underwent
      bilateral nerve-sparing RP, and were followed up for at least 18 months after RP.
      Patients received study drug for 27 weeks and completed the International Index
      of Erectile Function erectile function domain (EFD) questionnaire at baseline and
      serially after surgery. MAIN OUTCOME MEASURES: International Index of Erectile
      Function erectile function domain score. RESULTS: Data were available for 124
      patients (59 tacrolimus, 65 placebo); mean age was 54.6 +/- 6.2 years. No patient
      experienced permanent creatinine or potassium elevation. At baseline, mean EFD
      scores were 28.6 +/- 2.1 (tacrolimus group) and 29 +/- 1.5 (placebo group). By
      week 5, mean EFD scores had dropped to 8 +/- 9.4 (tacrolimus) and 9 +/- 10.7
      (placebo). At 18 months, mean EFD scores were 16.0 +/- 11.3 (tacrolimus) and 20.2
      +/- 9.0 (placebo) (P = .09). Tacrolimus failed to meet significance (hazard ratio
      = 0.83; P = .50), with no difference in: (i) percentage of patients achieving
      normal spontaneous erectile function (EFD score >=24), (ii) time to normalization
      of EFD score (>=24), (iii) percentage of patients capable of intercourse in
      response to phosphieserase type 5 inhibitor (PDE5i), and (iv) time to achieve
      response to PDE5i. CLINICAL IMPLICATIONS: Despite positive animal data, oral
      tacrolimus as used in this trial failed to improve erectile function after nerve
      sparing radical prostatectomy. STRENGTHS & LIMITATIONS: The study is limited by a
      high attrition rate. The strengths include a randomized, placebo controlled
      design, extensive patient monitoring, use of medication diaries and a validated
      instrument as the primary outcome measure. CONCLUSION: Despite supportive animal
      data, tacrolimus used in this fashion in the RP population failed to demonstrate
      any superiority over placebo. Mulhall JP, Klein EA, Slawin K, et al. A
      Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Utility of
      Tacrolimus (FK506) for the Prevention of Erectile Dysfunction Following Bilateral
      Nerve-Sparing Radical Prostatectomy. J Sex Med 2018;15:1293-1299.

PMID- 30224020
TI  - Deviance or Normalcy? The Relationship Among Paraphilic Thoughts and Behaviors,
      Hypersexuality, and Psychopathology in a Sample of University Students.
AB  - INTRODUCTION: The actual definitions of paraphilic thoughts or behaviors and
      hypersexuality are still a matter of debate in the scientific community, and few
      studies have evaluated their psychopathological correlates in non-clinical
      samples of both men and women. AIM: This study aimed at shedding light on the
      gender differences in terms of frequency of paraphilic fantasies and behaviors,
      and the relationship among paraphilias, hypersexuality, and general
      psychopathology. METHODS: A sample of 775 university students (243 men, 532
      women) was recruited from 6 Italian universities using questionnaires posted in
      social networks. Paraphilic behaviors, fantasies, and masturbation during these
      fantasies were evaluated, as well as hypersexuality, psychopathological
      correlates, self-perceived gender identity, and a history of adverse childhood
      conditions. MAIN OUTCOME MEASURES: Participants were assessed on the presence of
      paraphilic fantasies, behaviors, and masturbation related to paraphilic thoughts,
      and evaluated by means of the Symptom Checklist 90-Revised, the Hypersexual
      Disorder Screening Inventory, the International Index of Erectile Function, the
      Female Sexual Function Index, the Gender Identity/Gender Dysphoria Questionnaire,
      and the Childhood Experience of Care and Abuse Questionnaire. RESULTS: In the
      present survey, 50.6% of the men and 41.5% of the women reported at least 1
      behavior considered paraphilic. A gender difference in the prevalence of the main
      paraphilic interests and behaviors was observed, with men reporting a higher
      prevalence of voyeurism, exhibitionism, sadism, and frotteurism, and a higher
      prevalence of fetishism and masochism in women. Both general psychopathology and
      sexual dysfunctions were associated with hypersexuality, rather than with the
      content of sexual fantasies. Finally, an association between childhood
      adversities and hypersexuality was found in women but not in men. CLINICAL
      IMPLICATIONS: Understanding the psychopathological correlates of paraphilic
      fantasies/behaviors and hypersexuality may allow clinicians to develop specific
      psychological and pharmacological interventions. STRENGTHS & LIMITATIONS: This is
      one of the few studies assessing paraphilic phenomenology and psychopathological
      correlates of hypersexuality in a non-clinical sample of both men and women.
      CONCLUSION: The results seem to demonstrate that paraphilic thoughts and
      behaviors are not really a deviation from normalcy, rather they are quite
      widespread in the young population, and the distinction between healthy and
      pathological sexual interests may be better replaced by an all-encompassing
      approach considering ego-dystonic sexuality, hypersexuality, and their
      psychopathological correlates. Castellini G, Rellini AH, Appignanesi C, et al.
      Deviance or Normalcy? The Relationship Among Paraphilic Thoughts and Behaviors,
      Hypersexuality, and Psychopathology in a Sample of University Students. J Sex Med
      2018;15:1322-1335.

PMID- 30224021
TI  - Why Is Impaired Sexual Function Distressing to Men? Consequences of Impaired Male
      Sexual Function and Their Associations With Sexual Well-Being.
AB  - INTRODUCTION: According to theoretical models of sexual dysfunction, the complex
      association between male sexual function and subjective sexual well-being (ie,
      sexual satisfaction and distress) may be partially mediated by specific
      "consequences" of impaired function, but little research has assessed the
      frequency of specific consequences or their association with well-being. AIM: To
      pilot a scale assessing consequences of impaired male sexual function, and test
      whether specific consequences (eg, disruption of sexual activity, negative
      partner responses) mediated the association between sexual function and well
      being. METHODS: 166 men in sexually active heterosexual relationships completed
      self-report measures. A majority of men self-identified as experiencing impaired
      sexual function in the past month. MAIN OUTCOME MEASURE: Sexual Satisfaction
      Scale, International Index of Erectile Function, and Measure of Sexual
      Consequences. RESULTS: 17 specific consequences were reported with at least
      moderate frequency and were rated at least somewhat distressing. A factor
      analysis suggested 3 distinct categories of consequences: barrier to sex and
      pleasure, negative partner emotional responses, and impaired partner sexual
      function. These factors and the overall scale exhibited acceptable internal and
      test-retest reliability and each was significantly associated with multiple
      facets of sexual function and well-being. Frequency of sexual consequences
      significantly mediated the association between sexual function and well-being,
      with the strongest and most consistent indirect effects being found for the
      barrier to sex and pleasure factor. CLINICAL IMPLICATIONS: Consequences of
      impaired sexual function on one's sexual experiences may be an important
      maintaining factor of sexual dysfunction and reduction in these consequences may
      represent a mechanism of action for psychological treatments. STRENGTH AND
      LIMITATIONS: Strengths included a relatively large sample with a diverse range of
      sexual function and well-being, as well as modern statistical analyses to assess
      factor structure and mediation effects. Limitations included the use of self
      report scales with limited independent evidence of validity and reliability for
      use with male samples, as well as the cross-sectional methods that preclude
      strong conclusions regarding causal relationships. CONCLUSION: Sexual
      consequences represent potential maintaining factors of male sexual dysfunction
      and may represent key targets of cognitive behavioral treatments. Stephenson KR,
      Truong L, Shimazu L. Why is impaired sexual function distressing to men?
      Consequences of impaired male sexual function and their associations with sexual
      well-being. J Sex Med 2018;15:1336-1349.

PMID- 30224022
TI  - Changes in Adrenal Androgens During Puberty Suppression and Gender-Affirming
      Hormone Treatment in Adolescents With Gender Dysphoria.
AB  - INTRODUCTION: Gender-affirming hormone treatment is known to affect adrenal
      androgen levels in adult individuals with gender dysphoria (GD). This may be
      clinically relevant because the adrenal gland plays a critical role in many
      different metabolic processes. AIM: This study aims to assess the effects of
      gonadotropin-releasing hormone analogs (GnRHa) treatment and gender-affirming
      hormone treatment on adrenal androgen levels in adolescents with GD. METHODS: In
      this prospective study, dehydroepiandrosterone-sulfate (DHEAS) and
      androstenedione values were measured every 6 months during 2 years of GnRHa
      treatment only, and 2 years of GnRHa combined with gender-affirming hormone
      treatment (estradiol or testosterone) in 73 transgirls and 54 transboys. To
      determine trends in adrenal androgen levels a linear mixed model was used to
      approximate androgen levels. MAIN OUTCOME MEASURES: DHEAS and androstenedione
      levels were the main outcome measures. RESULTS: DHEAS levels rose in transboys
      during GnRHa treatment, which may represent the normal increase during
      adolescence. In transgirls no change in DHEAS levels during GnRHa treatment was
      found. Gender-affirming hormone treatment did not affect DHEAS levels in either
      sex. In transboys androstenedione levels decreased during the first year of GnRHa
      treatment, which may reflect reduced ovarian androstenedione synthesis, and rose
      during the first year of gender-affirming hormone treatment, possibly due to
      conversion of administered testosterone. In transgirls androstenedione levels did
      not change during either GnRHa or gender-affirming hormone treatment. CLINICAL
      IMPLICATIONS: No deleterious effects of treatment on adrenal androgen levels were
      found during approximately 4 years of follow-up. STRENGTHS & LIMITATIONS: This is
      one of the largest cohort of adolescents with GD, treated using a uniform
      protocol, with standardized follow-up. The lack of a control group is a
      limitation. CONCLUSION: The changes in androstenedione levels during GnRHa and
      gender-affirming hormone treatment in transboys may not be of adrenal origin. The
      absence of changes in androstenedione levels in transgirls or DHEAS levels in
      either sex during gender-affirming hormone treatment suggests that gender
      affirming hormone treatment does not significantly affect adrenal androgen
      production. Schagen SEE, Lustenhouwer P, Cohen-Kettenis PT, et al. Changes in
      Adrenal Androgens During Puberty Suppression and Gender-Affirming Hormone
      Treatment in Adolescents With Gender Dysphoria. J Sex Med 2018;15:1357-1363.

PMID- 30224023
TI  - Author Reply to Editorial Comment on "Novel Multimodal Analgesia Protocol
      Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis
      Patients".

PMID- 30224024
TI  - Editorial Commentary on "Novel Multimodal Analgesia Protocol Significantly
      Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients".

PMID- 30224025
TI  - Editorial Commentary: Does Desired Pregnancy During an Ovulatory Menstrual Cycle
      Hormonally Matter in the Man?

PMID- 30224026
TI  - A Brief Version of the Sexual Interest and Desire Inventory-Female With 4 Core
      Items.

PMID- 30224027
TI  - Quantitative peripheral muscle ultrasound in sepsis: Muscle area superior to
      thickness.
AB  - PURPOSE: The objective of this study is to describe the relationship between two
      quantitative muscle ultrasound measures, the rectus femoris cross-sectional area
      (RF-CSA) and quadriceps muscle thickness, with volitional measures of strength
      and function in critically ill patients with sepsis. MATERIALS AND METHODS: We
      performed a prospective study of patients admitted to a medical ICU with sepsis
      and shock or respiratory failure. We examined the association of two ultrasound
      measurements - the RF-CSA and quadriceps muscle thickness - with strength and
      function at day 7. Strength was determined using the Medical Research Council
      Score and function using Physical Function in the ICU Test, scored. RESULTS:
      Twenty-nine patients were enrolled; 19 patients had outcome testing performed.
      Over 7days, RF-CSA and thickness decreased by an average of 23.2% and 17.9%,
      respectively. The rate of change per day of RF-CSA displayed a moderate
      correlation with strength (rho 0.51, p-value 0.03) on day 7. Baseline and day 7
      RF-CSA did not show a significant correlation with either outcome. Quadriceps
      muscle thickness did not significantly correlate with either outcome.
      CONCLUSIONS: Muscle atrophy as detected by the rate of change in RF-CSA
      moderately correlated with strength one week after sepsis admission.

PMID- 30224029
TI  - 5-aminolevulinic acid photodynamic therapy for anal canal condyloma acuminatum: A
      series of 19 cases and literature review.
AB  - BACKGROUND: Anal canal condyloma acuminata are common, sexually transmitted
      lesions, most often caused by the human papillomavirus. The relatively high
      recurrence rate of anal canal condyloma acuminata can be attributed to the
      unsuccessful elimination of viruses in areas of subclinical and latent infection.
      This study aimed to observe and evaluate the effectiveness of 5-aminolevulinic
      acid-photodynamic therapy combined with monitoring of human papillomavirus load
      changes in patients with anal canal condyloma acuminata. METHODS: A total of 19
      patients with anal genital warts were recruited for this study. Firstly, visible
      warts around the anus were removed. Next, an anoscope examination was performed.
      Human papillomavirus detection, using real-time polymerase chain reaction assays,
      was performed before every cycle of treatment. Absorbent cotton rolls soaked with
      a concentration of 20% 5-aminolevulinic acid were inserted into the anus for 3 h.
      Finally, photodynamic therapy was applied to the lesions. Each patient required
      multiple PDT sessions to achieve complete response. RESULTS: All patients
      achieved complete clinical remission one week after the last session of
      treatment, and human papillomavirus loads decreased significantly. Six months
      follow-up after completion of therapy, none of the patients had recurrence.
      CONCLUSIONS: 5-aminolevulinic acid-photodynamic therapy is an effective and safe
      approach for anal canal condyloma acuminata. Dynamic human papillomavirus viral
      quantitative monitoring can aid in the evaluation of therapeutic effects and lead
      to better treatment outcomes.

PMID- 30224028
TI  - Adverse effects of long-term weight gain on microvascular endothelial function.
AB  - BACKGROUND: Endothelial dysfunction is the first stage of the atherosclerotic
      cascade, and independently associated with cardiovascular events. We evaluated
      the associations of longitudinal changes in weight, waist circumference, body fat
      percentage and lean mass index with changes in endothelial function. METHODS: 521
      community-based subjects who belonged to hypertensive sibships and had no history
      of myocardial infarction or stroke had their anthropometric measures and
      endothelial function assessed a mean of 8.5 years apart. Endothelial function was
      assessed with brachial artery ultrasound, yielding measures of flow-mediated
      dilation and reactive hyperemia. We used multivariable linear regression with
      generalised estimating equations to assess the associations of longitudinal
      changes (Delta) in anthropometric measures with Delta flow-mediated dilation and
      reactive hyperemia, adjusting for potential confounders. RESULTS: Mean+/-standard
      deviation age was 57.6+/-8.7years, 58% were women, and 72% were hypertensive.
      Most (84%) were overweight or obese at baseline. At end of follow-up, flow
      mediated dilation and reactive hyperemia increased by 1.9+/-7.6% and 51.2+/
      605.8% on average, respectively. In multivariable linear regression, changes in
      anthropometric measures were not associated with changes in flow-mediated
      dilation. However, Delta weight (beta+/-SE: -9.00+/-2.35), Delta waist
      circumference (-6.78+/-2.21) and Delta body fat percentage (-19.72+/-5.62,
      P<0.0001 for each) were inversely associated with Delta reactive hyperemia. Delta
      lean mass index was not associated with Delta reactive hyperemia. CONCLUSIONS:
      Long-term increases in weight, waist circumference and body fat percentage are
      associated with progressive worsening of microvascular endothelial function, but
      not conduit vessel endothelial function, in subjects without a history of
      cardiovascular events, independently of risk factors.

PMID- 30224030
TI  - Prognostic significance of left anterior fascicular block and its relation with
      coronary artery disease in old patients based on 570 autopsy cases.
AB  - BACKGROUND: Left Anterior Fascicular Block (LAFB) occurs frequently among the
      elderly, and have a correlation with coronary artery disease (CAD), yet
      controversies regarding its clinical significance still remain. METHODS: We
      carried on a retrospective study involving 92 LAFB and 478 non-LAFB patients, in
      which anatomic, clinical and electrocardiographic characteristics were compared.
      RESULTS: LAFB subjects had more pathological CAD (66.3% vs 54.6%, P = 0.039),
      myocardial infarction (MI) (53.3% vs 37.9%, P = 0.007) and myocarditis (5.4% vs
      1.7%, P = 0.043). Among the LAFB group, 58.1% of patients with CAD and 30.2% of
      patients with MI were clinically misdiagnosed, while 42.9% of patients with MI
      were clinically missed. Logistic regression showed CAD had no independent
      relevance with LAFB. LAFB subjects displayed heavier hearts [(451.1 +/- 101.3)g
      vs (407.1 +/- 102.3)g, P < 0.001], thicker left ventricular walls [(1.6 +/-
      0.4)cm vs (1.4 +/- 0.3)cm, P = 0.001]. Kaplan-Meier survival analysis indicated
      significant differences in long-term survival time (chi2 = 12.223, P < 0.001) and
      cardiac mortality (chi2 = 20.982, P < 0.001) between LAFB and non-LAFB group. Cox
      multivariate analysis demonstrated LAFB was an independent risk factor of all
      cause death (HR = 1.552, 95% CI = 1.208-1.994, P = 0.001) and cardiac death (HR =
      2.287, 95% CI = 1.545-3.386, P < 0.001). The major death cause of LAFB was
      cardiac death (46.7%), including more MI (28.3% vs 13.4%, P = 0.008), myocarditis
      (4.3% vs 1.0%, P = 0.042) and cardiac rupture (6.7% vs 1.9%, P = 0.022).
      CONCLUSIONS: LAFB subjects had more pathological CAD and MI, but LAFB was not an
      independent relevant factor of CAD. LAFB lowered the accuracy to clinically
      diagnose CAD. LAFB patients gained heavier hearts, thicker left ventricular
      walls, and suffered increased risk of death and cardiac death.

PMID- 30224032
TI  - Rise of first follow-up sodium in patients hospitalized with acute heart failure
      is associated with better outcomes.
AB  - INTRODUCTION: The prognostic effect of the direction of change in sodium (Na)
      level from admission to subsequent check in patients with acute heart failure
      (HF) has not been previously explored. METHODS: The ESCAPE trial data was
      utilized to study whether the rise of 1st follow-up Na (at day 3) relative to
      admission (among patients with admission hyponatremia) is associated with
      favorable outcomes. The study endpoints were all-cause rehospitalization and a
      composite of death, rehospitalization and cardiac transplant, both up to 6-month
      after discharge. RESULTS: Patients with rise of 1st follow-up Na (n = 43) had an
      average admission Na of 130.1 meq/L which increased to 134 meq/L at day 3 (P <
      0.001), while patients without rise of 1st follow up Na (n = 46) had an admission
      Na of 131 meq/L which decreased to 128.9 meq/L at day 3 (P < 0.001). There was an
      inverse association between the magnitude of change in Na level from admission to
      day 3 and the magnitude of change in blood urea nitrogen (BUN, r = -0.304, P =
      0.004), creatinine (r = -0.401, P < 0.001) and weight (r = -0.279, P = 0.011)
      during the same time frame. Among those 89 cases, 56 (63%) were rehospitalized
      and 70 (79%) experienced the composite endpoint. Patients without rise in 1st
      follow-up Na had higher frequency of rehospitalization (76.1% vs. 48.8%,
      univariate Odds ratio (OR) 1.778, 95% CI 1.174-2.693, P = 0.009) and composite
      endpoint (89.1% vs. 67.4%, univariate OR 1.779, 95% CI 1.208-2.619, P = 0.017),
      compared with those with Na rise. Cox regression analysis showed that rise in 1st
      follow-up Na was independently associated with reduced rehospitalization (Hazard
      ratio (HR) 0.429, 95% CI 0.191-0.960, P = 0.04) and the composite endpoint (HR
      0.430, 95% CI 0.201-0.920, P = 0.03) after covariate adjustment. CONCLUSION: Rise
      of first follow-up Na in patients with HF decompensation and hyponatremia on
      admission is associated with favorable intermediate-term outcomes.

PMID- 30224031
TI  - Prospective validation of prognostic and diagnostic syncope scores in the
      emergency department.
AB  - BACKGROUND: Various scores have been derived for the assessment of syncope
      patients in the emergency department (ED) but stay inconsistently validated. We
      aim to compare their performance to the one of a common, easy-to-use CHADS2
      score. METHODS: We prospectively enrolled patients >= 40 years old presenting
      with syncope to the ED in a multicenter study. Early clinical judgment (ECJ) of
      the treating ED-physician regarding the probability of cardiac syncope was
      quantified. Two independent physicians adjudicated the final diagnosis after 1
      year follow-up. Major cardiovascular events (MACE) and death were recorded during
      2 years of follow-up. Nine scores were compared by their area under the receiver
      operator characteristics curve (AUC) for death, MACE or the diagnosis of cardiac
      syncope. RESULTS: 1490 patients were available for score validation. The CHADS2
      score presented a higher or equally high accuracy for death in the long- and
      short-term follow-up than other syncope-specific risk scores. This score also
      performed well for the prediction of MACE in the long- and short-term evaluation
      and stratified patients with accuracy comparative to OESIL, one of the best
      performing syncope-specific risk score. All scores performed poorly for
      diagnosing cardiac syncope when compared to the ECJ. CONCLUSIONS: The CHADS2
      score performed comparably to more complicated syncope-specific risk scores in
      the prediction of death and MACE in ED syncope patients. While better tools
      incorporating biochemical and electrocardiographic markers are needed, this study
      suggests that the CHADS2-score is currently a good option to stratify risk in
      syncope patients in the ED. TRIAL REGISTRATION: NCT01548352.

PMID- 30224033
TI  - Metabolic substrate shift in human induced pluripotent stem cells during cardiac
      differentiation: Functional assessment using in vitro radionuclide uptake assay.
AB  - BACKGROUND: Recent developments in cellular reprogramming technology enable the
      production of virtually unlimited numbers of human induced pluripotent stem cell
      derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic
      hallmarks with endogenous cardiomyocytes, it remains a question as to what extent
      metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here
      we set out to functionally characterize the metabolic status of hiPSC-CM in vitro
      by employing a radionuclide tracer uptake assay. MATERIAL AND METHODS: Cardiac
      differentiation of hiPSC was induced using a combination of well-orchestrated
      extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling
      followed by WNT inhibition and lactate based cardiomyocyte enrichment. For
      characterization of metabolic substrates, dual tracer uptake studies were
      performed with 18F-2-fluoro-2-deoxy-d-glucose (18F-FDG) and 125I-beta-methyl
      iodophenyl-pentadecanoic acid (125I-BMIPP) as transport markers of glucose and
      fatty acids, respectively. RESULTS: After cardiac differentiation of hiPSCs, in
      vitro tracer uptake assays confirmed metabolic substrate shift from glucose to
      fatty acids that was comparable to those observed in native isolated human
      cardiomyocytes. Immunostaining further confirmed expression of fatty acid
      transport and binding proteins on hiPSC-CM. CONCLUSIONS: During in vitro cardiac
      maturation, we observed a metabolic shift to fatty acids, which are known as a
      main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential
      functional phenotype to investigate alteration of cardiac metabolism in cardiac
      diseases. Results also highlight the use of available clinical nuclear medicine
      tracers as functional assays in stem cell research for improved generation of
      autologous differentiated cells for numerous biomedical applications.

PMID- 30224034
TI  - Single-phase coronary artery CT angiography extracted from stress dynamic
      myocardial CT perfusion on third-generation dual-source CT: Validation by
      coronary angiography.
AB  - BACKGROUND: CT advances allow coronary arterial tree to be entirely covered
      during one CTP scan. Our aim was to investigate the potential value of single
      phase coronary CT angiography (SP-CCTA) extracted from stress dynamic myocardial
      CT perfusion (CTP) for coronary artery stenosis assessment. METHODS: Consecutive
      symptomatic patients were prospectively recruited and scanned with an ATP-stress
      dynamic myocardial CTP and routine CCTA protocol using third-generation DSCT.
      Noise reduction was applied to optimize image quality (IQ), the CTP phase with
      the best enhancement of the coronary arteries was selected as the SP-CCTA. IQ was
      assessed qualitatively. Using coronary angiography (CAG) as the reference
      standard, the diagnostic performance for stenosis detection was compared for SP
      CCTA and routine CCTA. RESULTS: 56 patients underwent the CTP and CCTA
      examination, among which 39 patients underwent CAG. The qualitative IQ scores of
      SP-CCTA were similar to that of routine CCTA (p > 0.05). On a per-segment basis,
      the sensitivity, specificity, positive predictive value, negative predictive
      value, diagnostic accuracy and area under the receiver-operating-characteristic
      curve results of SP-CCTA and routine CCTA for diagnosis of stenosis >=50%
      exhibited no significant difference (SP-CCTA: 78.1%, 94.9%, 77.4%, 95.1%, 91.6%
      and 0.935 vs. routine CCTA: 74.7%, 95.3%, 78.0%, 95.3%, 91.6% and 0.937; all p >
      0.05). The mean effective radiation dose of CTP and routine CCTA plus CTP were
      3.92 +/- 1.72 mSv and 5.98 +/- 2.01 mSv (p < 0.05), respectively. CONCLUSIONS:
      The IQ and diagnostic value of SP-CCTA was equivalent to routine CCTA on third
      generation DSCT. SP-CCTA images from CTP may potentially replace a separate
      routine CCTA, allowing the possibility of "one-stop" cardiac examination for high
      risk CAD patients who need myocardial ischemia assessment.

PMID- 30224035
TI  - Graves' disease and pregnancy.
AB  - This section deals with the specificities of managing Graves' disease during
      pregnancy. Graves' disease incurs risks of fetal, neonatal and maternal
      complications that are rare but may be severe: fetal hyper- or hypothyroidism,
      usually first showing as fetal goiter, neonatal dysthyroidism, premature birth
      and pre-eclampsia. Treatment during pregnancy is based on antithyroid drugs
      alone, without association to levothyroxine. An history of Graves' disease,
      whether treated radically or not, with persistent maternal anti-TSH-receptor
      antibodies must be well identified. Fetal monitoring should be initiated in a
      multidisciplinary framework that should be continued throughout pregnancy.
      Neonatal monitoring is also crucial if the mother still shows anti-TSH-receptor
      antibodies at end of pregnancy or underwent antithyroid treatment. The risk of
      recurrence of hyperthyroidism in the weeks following delivery requires maternal
      monitoring. The long-term neuropsychological progression of children of mothers
      with Graves' disease is poorly known.

PMID- 30224036
TI  - ?

PMID- 30224037
TI  - ?

PMID- 30224038
TI  - [Malnutrition in the elderly, screening and treatment].
AB  - Undernutrition is defined as an imbalance between the body's energy intake and
      requirements. It is present in 30 to 70% of hospitalised elderly people and its
      consequences are severe. Systematic screening and early treatment are an integral
      part of global geriatric care. The aetiological approach must be exhaustive
      (medico-psychosocial problems) and integrate difficulties related to the
      physiological ageing of the organism.

PMID- 30224039
TI  - [Nutritional requirements of the elderly].
AB  - The nutritional status of patients is based on knowledge of their specific needs
      and tools enabling them to be evaluated. The needs are qualitative and
      quantitative and must be adapted in certain situations such as the existence of
      an inflammatory syndrome. A systematic assessment of the nutritional status is an
      essential part of an elderly person's care in order to initiate preventive or
      corrective measures.

PMID- 30224040
TI  - [Swallowing disorders and the elderly in a geriatric care facility].
AB  - It is essential to fight against malnutrition and dehydration in elderly people
      in care facilities. They result in the deterioration of the general status, a
      risk of a fall, a risk of wounds, an increased risk of infection and mortality in
      geriatrics. In addition, swallowing disorders due to ageing increase the risk of
      food going down the wrong way. Those involved in the multidisciplinary care
      management pool their skills in support of the elderly person.

PMID- 30224041
TI  - [Food and nutrition liaison committees in healthcare facilities].
AB  - Since 2002, all healthcare facilities must have a food and nutrition liaison
      committee. The aim is to improve the management of food and nutrition related
      issues in hospital. The players concerned undertake a global and cross
      disciplinary approach to ensure better food, notably for elderly patients at risk
      of protein-energy malnutrition.

PMID- 30224042
TI  - [Centrifugal fruit and vegetable juicing, a resounding success].
AB  - It is essential to maintain a healthy diet adapted to every age of life, notably
      for the elderly. Indeed, several factors can harm this vital function. The
      installation of a fruit and vegetable centrifugal juicer in hospital, aside from
      its many benefits, was a resounding success with elderly people, their families
      and staff.

PMID- 30224043
TI  - [Discourse on life and Alzheimer's disease].
AB  - The discourse of a demented patient refers to an existential reality. It seeks to
      shape a meaning of life still shareable, to share a vision of oneself through the
      presence of the other. The conditions for facilitating expression and empathetic
      listening are discussed below.

PMID- 30224044
TI  - [Patients' expectations in a day hospital for frail elderly people].
AB  - The care management of frail elderly people must ensure that patients adhere to
      their personalised care and prevention plan. In order to optimise this adherence,
      it is essential to take into account the expectations of these aging population.
      This article presents the results of an analysis carried out by a nursing team
      regarding the expectations of patients in a day hospital for frail elderly
      people.

PMID- 30224045
TI  - [Playing to carry on living].
AB  - New technologies have a certain benefit for elderly people. By way of an example,
      the Wii games console not only favours an intergenerational bond but also the
      reconstruction of self-esteem. Rediscovering the pleasure of playing is essential
      for the body and mind of senior citizens.

PMID- 30224046
TI  - ?

PMID- 30224047
TI  - ?

PMID- 30224048
TI  - ?

PMID- 30224050
TI  - Water Distribution within Wild-Type NRas Protein and Q61 Mutants during
      Unrestrained QM/MM Dynamics.
AB  - Point mutations in p21ras are associated with ~30% of human tumors by disrupting
      its GTP hydrolysis cycle, which is critical to its molecular switch function in
      cellular signaling pathways. In this work, we investigate the impact of Gln 61
      substitutions in the structure of the p21N-ras active site and particularly focus
      on water reorganization around GTP, which appears to be crucial to evaluate
      favorable and unfavorable hydration sites for hydrolysis. The NRas-GTP complex is
      analyzed using a hybrid quantum mechanics/molecular mechanics approach, treating
      for the first time to our knowledge transient water molecules at the ab initio
      level and leading to results that account for the electrostatic coupling between
      the protein complex and the solvent. We show that for the wild-type protein,
      water molecules are found around the GTP gamma-phosphate group, forming an arch
      extended from residues 12 to 35. Two density peaks are observed, supporting
      previous results that suggest the presence of two water molecules in the active
      site, one in the vicinity of residue 35 and a second one stabilized by hydrogen
      bonds formed with nitrogen backbone atoms of residues 12 and 60. The structural
      changes observed in NRas Gln 61 mutants result in the drastic delocalization of
      water molecules that we discuss. In mutants Q61H and Q61K, for which water
      distribution is overlocalized next to residue 60, the second density peak
      supports the hypothesis of a second water molecule. We also conclude that Gly 60
      indirectly participates in GTP hydrolysis by correctly positioning transient
      water molecules in the protein complex and that Gln 61 has an indirect steric
      effect in stabilizing the preorganized catalytic site.

PMID- 30224049
TI  - Quantifying Platelet Margination in Diabetic Blood Flow.
AB  - Patients with type 2 diabetes mellitus (T2DM) develop thrombotic abnormalities
      strongly associated with cardiovascular diseases. In addition to the changes of
      numerous coagulation factors such as elevated levels of thrombin and fibrinogen,
      the abnormal rheological effects of red blood cells (RBCs) and platelets flowing
      in blood are crucial in platelet adhesion and thrombus formation in T2DM. An
      important process contributing to the latter is the platelet margination. We
      employ the dissipative particle dynamics method to seamlessly model cells,
      plasma, and vessel walls. We perform a systematic study on RBC and platelet
      transport in cylindrical vessels by considering different cell shapes, sizes, and
      RBC deformabilities in healthy and T2DM blood, as well as variable flowrates and
      hematocrit. In particular, we use cellular-level RBC and platelet models with
      parameters derived from patient-specific data and present a sensitivity study. We
      find T2DM RBCs, which are less deformable compared to normal RBCs, lower the
      transport of platelets toward the vessel walls, whereas platelets with higher
      mean volume (often observed in T2DM) lead to enhanced margination. Furthermore,
      increasing the flowrate or hematocrit enhances platelet margination. We also
      investigated the effect of platelet shape and observed a nonmonotonic variation
      with the highest near-wall concentration corresponding to platelets with a
      moderate aspect ratio of 0.38. We examine the role of white blood cells (WBCs),
      whose count is increased notably in T2DM patients. We find that WBC rolling or
      WBC adhesion tends to decrease platelet margination due to hydrodynamic effects.
      To the best of our knowledge, such simulations of blood including all blood cells
      have not been performed before, and our quantitative findings can help separate
      the effects of hydrodynamic interactions from adhesive interactions and
      potentially shed light on the associated pathological processes in T2DM such as
      increased inflammatory response, platelet activation and adhesion, and ultimately
      thrombus formation.

PMID- 30224052
TI  - Reminiscences on the "Classic" 1976 FRAP Article in Biophysical Journal.

PMID- 30224051
TI  - Actin Dynamics Couples Extracellular Signals to the Mobility and Molecular
      Stability of Telomeres.
AB  - Genome regulatory programs such as telomere functioning require extracellular
      signals to be transmitted from the microenvironment to the nucleus and chromatin.
      Although the cytoskeleton has been shown to directly transmit stresses, we show
      that the intrinsically dynamic nature of the actin cytoskeleton is important in
      relaying extracellular signals to telomeres. Interestingly, this mechanical
      pathway not only transmits physical stimuli but also chemical stimuli. The
      cytoskeletal network continuously reorganizes and applies dynamic forces on the
      nucleus and feeds into the regulation of telomere dynamics. We further found that
      distal telomeres are mechanically coupled in a length- and timescale-dependent
      manner and identified nesprin 2G as well as lamin A/C as being essential to
      regulate their translational dynamics. Finally, we demonstrated that such
      mechanotransduction events impinge on the binding dynamics of critical telomere
      binding proteins. Our results highlight an overarching physical pathway that
      regulates positional and molecular stability of telomeres.

PMID- 30224053
TI  - Intramolecular Diffusion in alpha-Synuclein: It Depends on How You Measure It.
AB  - Intramolecular protein diffusion, the motion of one part of the polypeptide chain
      relative to another part, is a fundamental aspect of protein folding and may
      modulate amyloidogenesis of disease-associated intrinsically disordered proteins.
      Much work has determined such diffusion coefficients using a variety of probes,
      but there has been an apparent discrepancy between measurements using long-range
      probes, such as fluorescence resonance energy transfer, and short-range probes,
      such as Trp-Cys quenching. In this work, we make both such measurements on the
      same protein, alpha-synuclein, and confirm that such discrepancy exists.
      Molecular dynamics simulations suggest that such differences result from a
      diffusion coefficient that depends on the spatial distance between probes.
      Diffusional estimates in good quantitative agreement with experiment are obtained
      by accounting for the distinct distance ranges probed by fluorescence resonance
      energy transfer and Trp-Cys quenching.

PMID- 30224055
TI  - Corrigendum to "Starved Escherichia coli preserve reducing power under nitric
      oxide stress" Biochemical and Biophysical Research Communications, Volume 476,
      Issue 115, July 2016, Pages 29-34.

PMID- 30224054
TI  - Molecular Determinants of Substrate Affinity and Enzyme Activity of a Cytochrome
      P450BM3 Variant.
AB  - Cytochrome P450BM3 catalyzes the hydroxylation and/or epoxidation of fatty acids,
      fatty amides, and alcohols. Protein engineering has produced P450BM3 variants
      capable of accepting drug molecules normally metabolized by human P450 enzymes.
      The enhanced substrate promiscuity has been attributed to the greater flexibility
      of the lid of the substrate channel. However, it is not well understood how
      structurally different and highly polar drug molecules can stably bind in the
      active site nor how the activity and coupling efficiency of the enzyme may be
      affected by the lack of enzyme-substrate complementarity. To address these
      important aspects of non-native small molecule binding, this study investigated
      the binding of drug molecules with different size, charge, polar surface area,
      and human P450 affinity on the promiscuous R47L/F87V/L188Q/E267V/F81I pentuple
      mutant of P450BM3. Binding free energy data and energy decomposition analysis
      showed that pentuple mutant P450BM3 stably binds (i.e., negative DeltaGb degrees
      ) a broad range of substrate and inhibitor types because dispersion interactions
      with active site residues overcome unfavorable repulsive and electrostatic
      effects. Molecular dynamics simulations revealed that 1) acidic substrates tend
      to disrupt the heme propionate A-K69 salt bridge, which may reduce heme oxidizing
      ability, and 2) the lack of complementarity leads to high substrate mobility and
      water density in the active site, which may lead to uncoupling. These factors
      must be considered in future developments of P450BM3 as a biocatalyst in the
      large-scale production of drug metabolites.

PMID- 30224056
TI  - Shikonin exerts anti-inflammatory effects in LPS-induced mastitis by inhibiting
      NF-kappaB signaling pathway.
AB  - Previous studies have shown that shikonin(SHI), the bioactive naphthoquinone
      constituent extracted from Chinese herb Lithospermum Erythrorhizon, possesses the
      potential to confront inflammation, and has little concerns towards drug residues
      comparing with antibiotics. While mastitis in dairy industry always trigger great
      harm to milk yields, effects of SHI on lipopolysaccharides (LPS)-induced mastitis
      should be measured. Here, we demonstrate anti-inflammatory effects of SHI on LPS
      challenged mastitis and elucidate the potential signaling pathway both in vivo
      and in vitro. As a result, SHI administration mice significantly suffered less
      impairment of mammary gland and less recruitment of neutrophils than LPS
      administration mice. SHI significantly suppressed the expression of p
      IkappaBalpha and p-p65, which are the critical proteins functioning in NF-kB
      signaling pathway. qPCR results indicate decreasing level of upstream pro
      inflammatory cytokines in tissues, such as TNF-alpha, IL-1beta, and IL-6. The
      results are corresponding with the results in vitro, suggesting the potential
      usage of SHI as a therapeutic medicine in mastitis.

PMID- 30224057
TI  - Atf3 induction is a therapeutic target for obesity and metabolic diseases.
AB  - Activating transcription factor 3 (Atf3) has been previously demonstrated to
      impact obesity and metabolism. However, a metabolic role of Atf3 in mice remains
      debatable. We investigated the role of Atf3 in mice and further investigated Atf3
      expression as a therapeutic target for obesity and metabolic diseases. Atf3
      knockout (KO) mice fed with a high fat diet (HFD) aggravated weight gain and
      impaired glucose metabolism compared to littermate control wild type (WT) mice.
      Atf3 KO aged mice fed with a chow diet (CD) for longer than 10 months also
      displayed increased body weight and fat mass compared to WT aged mice. We also
      assessed requirements of Atf3 in a phytochemical mediated anti-obese effect.
      Effect of sulfuretin, a previously known phytochemical Atf3 inducer, in
      counteracting weight gain and improving glucose tolerance was almost completely
      abolished in the absence of Atf3, indicating that Atf3 induction can be a
      molecular target for preventing obesity and metabolic diseases. We further
      identified other Atf3 small molecule inducers that exhibit inhibitory effects on
      lipid accumulation in adipocytes. These data highlight the role of Atf3 in
      obesity and further suggest the use of chemical Atf3 inducers for prevention of
      obesity and metabolic diseases.

PMID- 30224058
TI  - LINC01510 suppresses cell proliferation and invasion by inhibiting Wnt/beta
      catenin signaling in renal cell carcinoma.
AB  - The role of long non-coding RNA in Renal cell carcinoma (RCC) tumorigenesis and
      progression remains largely unknown. Here, we found that LINC01510 functions as a
      tumor suppressor in RCC tumorigenesis. We screened TCGA database and then found
      that LINC01510 is significantly down-regulated in malignant RCC tissues, and the
      lower expression of LINC01510 predicts poor prognosis. Moreover, the down
      regulated LINC01510 was further confirmed in our fresh tissues and cell lines.
      Biological functions assays shown that Ectopic expression of LINC01510 not only
      inhibits RCC cell proliferation both in vitro and in vivo, but also impairs cell
      invasion ability. Moreover, we found overexpression of LINC01510 inhibits the
      expression of CCND1 and CCNE1, as well as MMPs (MMP2, MMP7 and MMP9), and thus
      affecting RCC cell cycle and invasion. Meanwhile, Western blot assays revealed
      that the expression of beta-catenin is regulated by LINC01510; overexpression of
      beta-catenin could partly rescue the cell viability and invasion ability caused
      by ectopic expression of LINC01510. Taken together, we found that LINC01510
      regulates cell proliferation and invasion by modulating Wnt/beta-catenin
      signaling in RCC.

PMID- 30224059
TI  - Ca2+-dependent inhibition of branched-chain alpha-ketoacid dehydrogenase kinase
      by thiamine pyrophosphate.
AB  - Catabolism of the branched-chain amino acids (BCAAs: leucine, isoleucine, and
      valine) is regulated by the branched-chain alpha-ketoacid dehydrogenase (BCKDH)
      complex, which in turn is regulated by phosphorylation catalyzed by BCKDH kinase
      (BDK). Thiamine pyrophosphate (TPP) is required as a coenzyme for the E1
      component of the BCKDH complex and can also bring about activation of the complex
      by inhibiting BDK. The present study shows that free Ca2+ in the physiological
      range greatly increases the sensitivity of BDK to inhibition by TPP (IC50 of 2.5
      MUM in the presence of 1 MUM free Ca2+). This novel mechanism may be responsible
      for the stimulation of BCAA oxidation by conditions that increase mitochondrial
      free Ca2+ levels, e.g. in skeletal muscle during exercise.

PMID- 30224060
TI  - Upregulation of 24(R/S),25-epoxycholesterol and 27-hydroxycholesterol suppresses
      the proliferation and migration of gastric cancer cells.
AB  - Gastric cancer (GC) is one of the most common cancers and is the second-leading
      cause of cancer-associated morbidity worldwide. Oxysterols are oxidized
      derivatives of cholesterol that may be important in many biological processes,
      but the levels and roles of oxysterols in gastric tumours remain to be
      elucidated. The levels of cholesterol, oxysterols and sulfated oxysterols in
      human gastric tumour tissues, adjacent normal mucosal tissues, cancerous gastric
      juice and gastric juice obtained from healthy subjects were detected by LC-MS. It
      was found that the levels of 24(R/S),25-EC and 27HC in human gastric tumour
      tissues and cancerous gastric juice were significantly increased compared with
      those of adjacent normal mucosal tissues and gastric juice from healthy subjects.
      Compared with normal gastric mucosal tissue, the levels of sulfated 25
      hydroxycholesterol (25HC3S) and the ratio of 25HC3S/25HC were decreased in human
      gastric tumour tissues, which might be related to the dramatically decreased
      SULT2A1 expression in gastric tumour tissue. Both 24(R/S),25-EC and 27HC
      suppressed gastric cancer proliferation, which was not altered by LXRalpha-siRNA
      treatment. The suppression of cell proliferation induced by 27HC was attenuated
      by LXRbeta-siRNA, but the suppression of cell proliferation induced by 24(R/S),25
      EC was intensified by LXRbeta-siRNA. Both 24(R/S),25-EC and 27HC dramatically
      inhibited HGC-27 cell migration, which was attenuated by the co-transfection of
      cells with LXRalpha-siRNA and LXRbeta-siRNA, but not LXRalpha-siRNA or LXRbeta
      siRNA alone. In conclusion, the accumulated 24(R/S),25-EC and 27HC in human
      gastric tumour tissues might play important roles in gastric cancer development.

PMID- 30224061
TI  - Two different restriction-modification systems for degrading exogenous DNA in
      Paenibacillus polymyxa.
AB  - Accompanied by benefits from horizontally transferred genes, bacteria have to
      face the risk of the invasion of dangerous genes. Bacteria often use the
      restriction-modification (R-M) system, which is consisted of methyl transferase
      (MEase) and restrictase (REase), to protect self-DNA and defend against foreign
      DNA. Paenibacillus polymyxa, widely used as growth promoting rhizobacteria in
      agriculture, can also produce compounds of medical and industrial interests. It
      is unclear whether R-M systems exist in P. polymyxa. In this study, we used a
      shuttle plasmid with epigenetic modification from different bacteria to explore R
      M systems in P. polymyxa. We found that DNA which is methylated by DNA adenine
      methyltransferase (Dam) in E. coli was strongly restricted, indicating the
      presence of a Dam-methylation-dependent R-M system in P. polymyxa. Whereas, DNA
      from a dam-E. coli strain was also moderately restricted, indicating the presence
      of a Dam-methylation-independent R-M system. Degradation of plasmid DNA with Dam
      methylation by cell-free protein extract of P. polymyxa provides additional
      evidence for the presence of Dam-methylation-dependent R-M system. Taken
      together, our work showed that there are two different types of R-M system in P.
      polymyxa, providing a foundation for the study of innate immunity in P. polymyxa
      and for the development of genetic engineering tools in P. polymyxa.

PMID- 30224063
TI  - Leonurine hydrochloride promotes osteogenic differentiation and increases
      osteoblastic bone formation in ovariectomized mice by Wnt/beta-catenin pathway.
AB  - Leonurine hydrochloride (LH) is a synthetic chemical compound derived from
      leonurine that can be extracted from Leonurus sibiricus and possesses
      antioxidant, anti-apoptosis, and neuroprotective activities. In previous studies,
      LH has been demonstrated to attenuate osteoclast activity and prevent bone loss.
      However, it is unknown whether LH accelerates bone formation and promotes
      osteogenic differentiation. We systematically examined the effects of LH on
      ovariectomized-induced osteoporotic mice and the MC3T3-E1 osteoblastic cell line.
      The results revealed that LH enhanced differentiation of MC3T3-E1 cells, with a
      dose-dependent increase in alkaline phosphatase (ALP) activity. Moreover, LH
      upregulated osteogenesis-related gene expression, including osterix, alpha 1 type
      1 collagen, runt-related transcription factor 2 (Runx2) and ALP, as shown by
      quantitative reverse transcription-polymerase chain reaction analysis. At the
      same time, elevated expression of low-density lipoprotein receptor-related
      protein 5 and beta-catenin mRNA was detected in the Wnt/beta-catenin pathway. A
      western blot analysis revealed that LH dose-dependently increased the expression
      of Runx2 and beta-catenin, and promoted phosphorylation of glycogen synthase
      kinase-3beta in vitro. The in vivo results showed that administering LH (15
      mg/kg/d) for 8 weeks alleviated destruction of the trabecular microstructure
      caused by osteoporosis. LH increased the bone mineral density and trabecular
      number, decreased trabecular separation according to a micro-computed tomography
      scan. In addition, LH enhanced the expression of beta-catenin and Runx2 in vivo.
      In conclusion, LH promoted osteogenic differentiation and bone formation in vivo
      and in vitro, which alleviated osteoporosis through activation of the Wnt/beta
      catenin pathway.

PMID- 30224062
TI  - Stromal interaction molecule 1 is required for neonatal testicular development in
      mice.
AB  - Stromal interaction molecule 1 (STIM1) is a transmembrane endoplasmic reticulum
      protein, and it serves as a Ca2+ sensor and activator of store-operated Ca2+
      entry (SOCE). We have previously identified STIM1 in the proteome profile of mice
      neonatal testes, revealing STIM1 to be associated with neonatal testicular
      development. Here, to further explore the location and function of STIM1 in mice
      testes, we studied the effect of Stim1 gene knockdown on neonatal testicular
      development by testicular culture. Our results revealed that STIM1 was primarily
      located in Sertoli cells. Knockdown of Stim1 gene using morpholino in neonatal
      testis caused the mislocation of Sertoli cells and loss of germ cells, which were
      associated with the aberrant reactive oxygen species (ROS) activation, while
      inhibition of ROS could partly rescue the phenotypes caused by Stim1 gene
      knockdown. In conclusion, our study suggests that STIM1 can maintain neonatal
      testicular development by inhibiting ROS activation.

PMID- 30224064
TI  - Severe hypoxia increases expression of ATM and DNA-PKcs and it increases their
      activities through Src and AMPK signaling pathways.
AB  - BACKGROUND: Solid tumors often contain hypoxic regions because an abnormal and
      inefficient tumor vasculature is unable to supply sufficient oxygen. Tissue
      hypoxia is generally defined as a low oxygen concentration of less than 2%. It is
      well known that tumor cells under severe hypoxia, where oxygen concentration is
      less than 0.1%, show radioresistance. It has been reported that cells under
      severe hypoxia show different responses from those under mild hypoxia, where
      oxygen concentration is 0.5-2.0%. In the present study, we investigated the
      effects of severe hypoxia on expression and activities of ATM and DNA-dependent
      protein kinase catalytic subunit (DNA-PKcs), both of which regulate DNA double
      strand breaks (DSBs) repair and radiation sensitivity. Signaling pathways for
      increasing expression and activities of ATM and DNA-PKcs under severe hypoxia
      were also investigated. METHODS: SV40-transformed human fibroblast cell lines,
      LM217 and LM205, and normal human dermal fibroblasts (NHDF) were used. Cells were
      cultured at an oxygen concentration of less than 0.05% for 12 or 24 h. Activities
      and/or expression of ATM, DNA-PKcs, Src, Caveolin-1, EGFR, HIF-1alpha, PDK1, Akt,
      AMPKalpha, and mTOR were estimated by Western blot analyses. RESULTS: Severe
      hypoxia increased expression and activities of ATM, DNA-PKcs, Src, Caveolin-1,
      EGFR, PDK1, Akt, and AMPKalpha, and decreased expression and activity of mTOR. A
      specific Src inhibitor, PP2 suppressed activation of ATM, DNA-PKcs, Caveolin-1,
      EGFR, and Akt under severe hypoxia. Treatment with siRNA for AMPKalpha suppressed
      activation of ATM and DNA-PKcs and increase of ATM expression under severe
      hypoxia. CONCLUSION: Our data show that severe hypoxia increases activities of
      ATM and DNA-PKcs through Src and AMPK signaling pathways, and that activation of
      AMPK under hypoxia causes increase of ATM expression. Since ATM and DNA-PKcs play
      important roles in DSBs repair induced by ionizing radiation, those data provide
      novel insights on the molecular mechanism of the cellular radioresistance under
      severe hypoxia.

PMID- 30224065
TI  - ERp44 depletion exacerbates ER stress and aggravates diabetic nephropathy in
      db/db mice.
AB  - Diabetic nephropathy (DN) is a major complication of diabetes, and the
      dysfunction of endoplasmic reticulum (ER) plays an important role in its
      pathogenesis. ERp44, an ER resident chaperone protein, has been implicated in the
      modulation of ER stress, however, its role and mechanism in DN are not
      determined. Here, we show that ERp44 expression is upregulated in the glomeruli
      of db/db mice, a rodent model of type 2 diabetes. When ERp44 is depleted by in
      vivo shRNA-mediated knockdown, the features associated with DN including
      albuminuria level and glomerular basement membrane (GBM) thickness are
      aggravated, therefore suggesting a detrimental role of ERp44 depletion in DN
      progression. We further show that ERp44 depletion exacerbates ER stress in DN in
      db/db mice, and that attenuating ER stress with the chemical chaperone TUDCA
      remarkably diminishes the aggravated DN features caused by ERp44 depletion. These
      results suggest that the exacerbated ER stress is a critical factor for the
      detrimental effect of ERp44 depletion on DN progression in db/db mice. Thus, our
      study links the role of ERp44 in DN with ER stress regulation and may offer a
      potential therapeutic strategy to interfere DN progression.

PMID- 30224067
TI  - Effect of growth differentiation factor-15 secreted by human umbilical cord blood
      derived mesenchymal stem cells on amyloid beta levels in in vitro and in vivo
      models of Alzheimer's disease.
AB  - Alzheimer's disease (AD), which is the most common progressive neurodegenerative
      disease, causes learning and memory impairment. The pathological progress of AD
      can derive from imbalanced homeostasis of amyloid beta (Abeta) in the brain. In
      such cases, microglia play important roles in regulating the brain Abeta levels.
      In the present study, we found that human umbilical cord blood-derived
      mesenchymal stem cells (hUCB-MSCs) can increase, through paracrine action, the
      ability of microglial cells to clear Abeta. In order to identify the associated
      paracrine factors, a secretome of hUCB-MSCs co-cultured with Abeta-treated BV2
      microglial cells was analyzed using a human cytokine protein array. As a result,
      growth differentiation factor-15 (GDF-15) was identified as a predominant
      candidate, and its association with Abeta clearance by microglial cells was
      investigated in vitro and in a 5XFAD mouse model. When Abeta-treated BV2 cells
      were treated with exogenous recombinant GDF-15, the Abeta levels in the culture
      medium decreased. Moreover, GDF-15 injection in the brain parenchyma of 5XFAD
      mice also led to decrease in Abeta plaques. In contrast, co-culture of BV2 cells
      and hUCB-MSCs treated with GDF-15-specific siRNA did not influence the Abeta
      levels in the culture medium. To elucidate how these phenomena are related, we
      confirmed that GDF-15 specifically increases insulin-degrading enzyme (IDE)
      expression in microglial cells through TGFbeta receptor type II (TGFbetaRII),
      both in vitro and in vivo. These findings suggest that hUCB-MSCs promote the
      Abeta clearance ability of microglial cells through regulation of GDF-15
      secretion, thus elucidating a therapeutic mechanism for AD.

PMID- 30224066
TI  - NanoSIMS imaging reveals unexpected heterogeneity in nutrient uptake by brown
      adipocytes.
AB  - Heterogeneity in the metabolic properties of adipocytes in white adipose tissue
      has been well documented. We sought to investigate metabolic heterogeneity in
      adipocytes of brown adipose tissue (BAT), focusing on heterogeneity in nutrient
      uptake. To explore the possibility of metabolic heterogeneity in brown
      adipocytes, we used nanoscale secondary ion mass spectrometry (NanoSIMS) to
      quantify uptake of lipids in adipocytes interscapular BAT and perivascular
      adipose tissue (PVAT) after an intravenous injection of triglyceride-rich
      lipoproteins (TRLs) containing [2H]triglycerides (2H-TRLs). The uptake of
      deuterated lipids into brown adipocytes was quantified by NanoSIMS. We also
      examined 13C enrichment in brown adipocytes after administering [13C]glucose or
      13C-labeled mixed fatty acids by gastric gavage. The uptake of 2H-TRLs-derived
      lipids into brown adipocytes was heterogeneous, with 2H enrichment in adjacent
      adipocytes varying by more than fourfold. We also observed substantial
      heterogeneity in 13C enrichment in adjacent brown adipocytes after administering
      [13C]glucose or [13C]fatty acids by gastric gavage. The uptake of nutrients by
      adjacent brown adipocytes within a single depot is variable, suggesting that
      there is heterogeneity in the metabolic properties of brown adipocytes.

PMID- 30224068
TI  - Identifying maltreatment subgroups with patterns of maltreatment subtype and
      chronicity: A latent class analysis approach.
AB  - Maltreatment experiences are complex, and it is difficult to characterize the
      heterogeneity in types of maltreatment. Subtypes, such as emotional maltreatment,
      sexual abuse, physical abuse, and neglect commonly co-occur and may persist
      across development. Therefore, treating individual maltreatment subtypes as
      independently occurring is not representative of the nature of maltreatment as it
      occurs in children's lives. Latent class analysis (LCA) is employed herein to
      identify subgroups of maltreated children based on commonalities in maltreatment
      subtype and chronicity. In a sample of 674 low-income urban children, 51.6% of
      whom experienced officially documented maltreatment, our analyses identified four
      classes of children, with three distinct classes based on maltreatment subtypes
      and chronicity, and one group of children who did not experience maltreatment.
      The largest class of maltreated children identified was the chronic, multi
      subtype maltreatment class (57% of maltreated children); a second class was
      characterized by only neglect in a single developmental period (31% of maltreated
      children), and the smallest class was characterized by a single subtype of
      maltreatment (emotional maltreatment, physical, or sexual abuse) occurring in a
      single developmental period (12% of maltreated children). Characterization of
      these groups confirms the overlapping nature of maltreatment subtypes. There were
      notable differences between latent classes on child behavioral and socio
      emotional outcomes measured by child self-report and camp counselors report
      during a one-week summer camp. The largest differences were between the non
      maltreated class and the chronic maltreatment class. Children who experienced
      chronic, multi-subtype maltreatment showed higher levels of externalizing
      behavior, emotion dysregulation, depression, and anxiety.

PMID- 30224069
TI  - Disparities in peptic ulcer disease: A nationwide study.
AB  - BACKGROUND: While advances in diagnosis and treatment of peptic ulcer disease
      have led to a decrease in hospital admissions the socioeconomic distribution of
      these benefits is unknown. METHODS: We designed a retrospective cohort study
      using the National Inpatient Sample from 2012 to 2013 including all patients that
      were admitted for peptic ulcer disease. We compared the types of ulcer related
      complications, the rates of intervention and the outcomes based on race and
      insurance status. RESULTS: Of 42,046 patients admitted for peptic ulcer disease
      80.25% had an ulcer related complication. Black patients had the lowest rates of
      bleeding and highest rates of perforation and were less likely to undergo surgery
      for their complication but mortality was not different from white patients.
      Uninsured patients also had lower rates of bleeding and higher rates of
      perforation and they were at increased risk for death. CONCLUSIONS: Unlike other
      surgical conditions insurance status, not race, predicts mortality in peptic
      ulcer disease.

PMID- 30224070
TI  - The role of preoperative therapy prior to pancreatoduodenectomy for distal
      cholangiocarcinoma.
AB  - BACKGROUND: Although increasingly administered to patients with pancreatic ductal
      adenocarcinoma, the role of preoperative therapy for patients with distal
      cholangiocarcinoma is undefined. METHODS: All patients with distal
      cholangiocarcinoma who underwent pancreatoduodenectomy between 1999 and 2014 were
      retrospectively reviewed. Differences in clinicopathologic characteristics and
      overall survival (OS) were compared between patients who underwent surgery de
      novo and those who received preoperative therapy. RESULTS: Twenty-one patients
      (46.7%) received preoperative therapy and 24 (53.3%) did not. Five-year OS rates
      were not statistically significantly different between patients who received
      preoperative therapy and those who did not (46.6% vs 49.1%, p > 0.05). On
      multivariate cox proportional hazards analysis, lymph node positivity was the
      strongest predictor of OS (HR 4.68 (95%CI 1.52-14.42)). Whereas preoperative
      therapy was not associated with improved OS (HR 1.06 (95%CI 0.42-2.66)), the
      receipt of either pre- or post-operative therapy was (HR 0.40 (95%CI 0.16-1.00)).
      CONCLUSION: While these results do not support the routine administration of
      preoperative therapy to patients with distal cholangiocarcinoma, it may be an
      alternative treatment strategy appropriate for a subset of patients with high
      risk clinical or pathologic features.

PMID- 30224071
TI  - Resident-as-teacher programs in general surgery residency - A review of published
      curricula.
AB  - INTRODUCTION: The Liaison Committee on Medical Education (LCME) requires that
      residents are trained to fulfill their educational duties toward medical
      students. This study reviews the literature on resident-as-teacher programs
      (RATPs) aimed at surgical residents. METHODS: Literature search with MeSH terms
      internship, residency, general surgery, teaching, education, and curriculum was
      performed using PubMed, Embase, Web of Science, and ERIC. Curriculum components
      and how curricula's success was measured were extracted for each study. Quality
      was scored using the Medical Education Research Study Quality Instrument
      (MERSQI). RESULTS: For the seven relevant publications the average MERSQI score
      was 9.9 (range 6.5-13.5). The RATPs were either lecture based (4/7) or content
      was distributed electronically (3/7). Change in attitude toward teaching was the
      most frequently assessed outcome. Highly rated curricular components were
      individualized feedback and iterative reminders to make teaching part of
      practice. CONCLUSIONS: Few published RATPs in general surgery training exist. The
      literature suggests that pairing lectures with observation and feedback is
      successful. Distributing the content electronically is a feasible alternative to
      class-room based teaching in a busy surgical residency.

PMID- 30224072
TI  - Resident perceptions and evaluations of fellow-led and resident-led surgical
      services.
AB  - BACKGROUND: The impact of fellowship training on general surgery residency has
      remained challenging to assess. Surgical resident perceptions of fellow-led and
      resident-led surgical services have not been well described. METHODS:
      Retrospective cross-sectional data were collected from residents' service
      evaluations from 7/2014 through 7/2017. Surgical services were categorized as
      resident-led or fellow-led. 31 variables were evaluated and collapsed into 7
      factors including clinical experience, educational experiences, clinical staff,
      workload, feedback, treatment of residents, and overall rotation. RESULTS: Among
      all PGY levels, fellow-led surgical services were rated significantly higher (p <
      0.05) regarding clinical experience, clinical staff, treatment of residents, and
      overall rotation. PGY1-2 residents rated resident-led services significantly
      higher in the area of educational experiences, while PGY 3 residents rated
      resident-led services higher in the area of workload. However, PGY4-5 residents
      rated fellow-led services significantly higher in all 7 categories. Individual
      fellow-led services were rated significantly higher for various categories at
      different PGY levels. CONCLUSIONS: Surgical residents appear to value the
      educational experiences of fellow-led services. Each fellow-led service may
      ultimately provide unique educational opportunities and resources for different
      PGY levels.

PMID- 30224073
TI  - Preoperative goal setting and perioperative communication in an academic training
      institution: Where do we stand?
AB  - BACKGROUND: We collected data regarding specific aspects of perioperative
      surgical education within our institution's Section of Surgical Sciences as a
      needs assessment. METHODS: Categorical general surgery residents and attending
      surgeons were queried regarding their perceptions of resident preoperative
      planning and perioperative communication. RESULTS: The overall response rate was
      81%, with 35 resident and 54 faculty respondents. Residents reported selecting an
      operative learning objective a median of 50% (IQR 36-67) of the time, whereas
      attending surgeons perceived this to be the case a median of 26% (IQR 15-35) of
      the time (P < 0.001). The group reported median frequencies of 20% (IQR 9-31) for
      preoperative discussion of learning objectives, 12% (IQR 4-27) for preoperative
      discussion of competence and 27% (IQR 17-55) for postoperative debriefing.
      CONCLUSIONS: This study demonstrates deficits in resident goal setting and
      perioperative communication within our program, which are targets for future
      intervention. We share these results as a potential tool for other programs.

PMID- 30224074
TI  - The current State of the acute care surgery workforce: A boots on the ground
      perspective.
AB  - BACKGROUND: Acute care surgery (ACS) was proposed to address a general surgery
      workforce crisis; however, the ACS workforce composition is unknown. A national
      survey was conducted to determine the differences in the emergency general
      surgery (EGS) workforce between ACS and non-ACS hospitals. METHODS: The American
      Hospital Association (AHA) Annual Survey of Hospitals database was queried to
      identify acute care general hospitals. A hybrid mail/electronic survey was sent
      to 2811 acute care hospitals that met the inclusion criteria of hospitals that
      care for adult patients (>=18 years old) with an emergency room (ER), >= 1
      operating room (OR), and 24-h ER access. Hospitals were queried on whether they
      utilized an ACS model. The workforce composition among ACS and non-ACS hospitals
      was evaluated using X2 tests, t tests, and Wilcoxon rank-sum tests. RESULTS:
      Survey response was 60% (N = 1690). ACS hospitals had a higher proportion of
      emergency surgeons who were female (20% vs. 14%, p < 0.0001), newly-trained (17%
      vs 10%, p < 0.0001), critical care trained (78% vs. 31%, p < 0.0001), and who had
      an additional degree (35% vs. 13%, p < 0.0001). More ACS hospitals had 24/7 in
      house OR nursing staff (72% vs. 15%, p < 0.0001) and ancillary staff.
      CONCLUSIONS: ACS and non-ACS hospitals differ in their surgical workforce. It is
      clear that ACS hospitals have more human capital, which suggests that ACS
      hospitals may require more dedicated resources compared to non-ACS hospitals.

PMID- 30224075
TI  - Jejunostomy tubes: A solution in search of the problem.

PMID- 30224077
TI  - [Treatment of infantile hemangioma in Togo].

PMID- 30224076
TI  - Exosomes derived from bone marrow mesenchymal stem cells overexpressing microRNA
      25 protect spinal cords against transient ischemia.
AB  - OBJECTIVE: We investigated the neuroprotection of exosomes derived from bone
      marrow mesenchymal stem cells overexpressing microRNA-25 on ischemic spinal
      cords. METHODS: Cultured mesenchymal stem cells were transfected with lentivirus
      vectors containing pre-microRNA-25 or control vectors. Exosomes were isolated and
      harvested by centrifugation. Spinal cord ischemia was induced in rats by
      crossclamping the descending aorta just distal to the left subclavian artery for
      15 minutes. Exosomes from mesenchymal stem cells, mesenchymal stem cells
      transfected with control vector, or pre-microRNA-25 were administered by
      intrathecal injection before ischemia. Hind-limb motor function was assessed with
      the motor deficit index. Contents of interleukin-1beta, tumor necrosis factor
      alpha, malondialdehyde, and superoxide dismutase activity were measured using
      commercial kits. Expressions of NADPH oxidase 2, NADPH oxidase 4, and microRNA-25
      were detected by Western blot and quantitative reverse transcription polymerase
      chain reaction. Lumbar spinal cords were harvested for histologic examination.
      RESULTS: Transfection of pre-microRNA-25 significantly enhanced microRNA-25
      levels in mesenchymal stem cells and their exosomes (P < .001). All exosome
      pretreating groups exhibited lower levels of interleukin-1beta and tumor necrosis
      factor-alpha (P < .001), more intact motor neurons (P < .001), and lower motor
      deficit index scores (P < .005) than those of controls. Compared with exosomes,
      microRNA-25-enriched exosomes markedly enhanced microRNA-25 level (P < .001),
      inhibited NADPH oxidase 4 expression (P = .012), but not NADPH oxidase 2
      expression, decreased malondialdehyde content (P = .022), increased superoxide
      dismutase activity (P < .001) in spinal cords, and had additional neuroprotective
      effects as evidenced by lower motor deficit index scores (P < .005) and more
      survival neurons (P = .002). CONCLUSIONS: The neuroprotection of exosomes from
      mesenchymal stem cells on ischemic spinal cords can be enhanced by genetic
      modification of the exosomes to contain elevated microRNA-25.

PMID- 30224078
TI  - [Acne flare on isotretinoin: A pointer to diagnosis of hidradenitis suppurativa].
AB  - BACKGROUND: Isotretinoin is the most potent treatment for acne but paradoxical
      flares can occur. HS lesions of the face may be mistaken for acne. We report on 4
      patients in whom an "acne" flare on isotretinoin led to the correct diagnosis of
      HS. PATIENTS AND METHODS: Four young male patients aged 15 to 28 years were
      referred to us because of an acne flare on isotretinoin. Three of them had
      clinical features considered unusual in acne : involvement of the nape of the
      neck (2), retroauricular cysts (2), a rope-like pre-sternal lesion (1), a large
      bag-like sinus on the face (1), large deep depressed U-type scars on the back
      (3). Questioning revealed that all three had previously experienced several
      attacks of inflammatory nodules in the axillae and/or inguinal folds; they had
      not mentioned these lesions since they seemed so minor. The fourth patient had
      lesions typical of HS comprising nodules, sinus, rope-like hypertrophic scars on
      the face mistaken for acne, epidermal cysts on the scrotum and pubic
      folliculitis. Treatment with systemic antibiotics resulted in regression of
      lesions in all 4 patients. DISCUSSION: An acne flare on isotretinoin requires
      investigations with a view to potential diagnosis of HS. Patients presenting
      "acne" and atypical features such as involvement of the neck, large U scars and
      cord-like structures should be questioned about the presence of nodules in the
      axillae and groin since patients with mild HS may not spontaneously acknowledge
      such typical symptoms.

PMID- 30224079
TI  - Neutrophilic urticarial dermatosis: A review.
AB  - Neutrophilic urticarial dermatosis (NUD) is a rare form of dermatosis. In
      clinical terms, it consists of a chronic or recurrent eruption comprising
      slightly elevated, pink to reddish plaques or macules. The elementary lesion
      lasts 24 to 48hours and resolves without leaving any residual pigmentation. Extra
      cutaneous signs are common, particularly fever or arthralgia. At histopathology,
      the dermis contains dense neutrophilic interstitial infiltrate with
      leukocytoclasis, but without fibrinoid necrosis of vessel walls. NUD often occurs
      in a setting of underlying systemic disease. The most commonly associated
      diseases are adult-onset Still's disease, Schnitzler syndrome, lupus
      erythematosus and cryopyrin-associated periodic syndromes. Treatment of NUD
      depends on the clinical context. Dapsone and colchicine are often effective.

PMID- 30224080
TI  - [Immune checkpoint blockade in oncodermatology: An ongoing revolution].

PMID- 30224081
TI  - Advocacy for use of the modified Iowa Level of Assistance Scale for clinical use
      in patients after hip replacement: an observational study.
AB  - OBJECTIVES: To test the internal consistency and item difficulty of the modified
      Iowa Level of Assistance Scale (mILAS). DESIGN: Retrospective observational
      study. SETTING: Two orthopaedic wards of two general hospitals. PARTICIPANTS:
      Following elective primary unilateral total hip replacement surgery, all
      participants performed mILAS activities that were scored daily to assess their
      recovery of activities during hospitalisation. MAIN OUTCOME MEASURES: The
      internal consistency and the level of assistance needed by the patient (item
      difficulty) of the mILAS were calculated using data from Deventer Hospital,
      Deventer, the Netherlands (n=255). A cross-validation was performed using data
      from Nij Smellinghe Hospital, Drachten, the Netherlands (n=224). RESULTS: The
      internal consistency of the mILAS was acceptable on all three postoperative days
      (alpha=0.84 to 0.97). Cronbach's alpha and Rasch analysis revealed a misfit of
      stair climbing with the other items of the mILAS. The item difficulty of the
      mILAS items changed over the first two postoperative days. During the first three
      postoperative days, the sit to supine transfer was generally the most difficult
      item to achieve, and the sit to stand transfer was the least difficult item to
      achieve as rated by physiotherapists. The cross-validation analysis revealed
      similar results. CONCLUSIONS: The mILAS is a clinically sound measurement tool to
      assess the ability of patients to perform five functional tasks safely during
      hospitalisation. Stair climbing appears to be the easiest item to complete, and
      the sit to supine transfer is generally the most difficult after surgery.

PMID- 30224082
TI  - A new side-looking downhole magnetic resonance imaging tool.
AB  - In general, only the depth information can be acquired using the centralized
      downhole NMR tools. The radial profile information is equally important to the
      depth. Improving the pad tools, also called side-looking tools, is the
      appropriate direction for solving this problem. The side-looking downhole
      measurement can provide depth and radially resolved information of the reservoir.
      In this research a new side-looking tool which includes main magnets and pre
      polarized magnets has been designed and built. The pre-polarized magnets in both
      sides are used to adjust the homogeneity of magnetic field along the length
      direction of the instrument and polarize the samples when the tool is moving up
      and down along the borehole with a speed up to 500 m/h. A winding coil with
      several frequencies corresponding to different depths has been designed to match
      the static magnetic field. The sensitive region of this tool is about one-third
      of a hollow cylinder at every frequency which gives a side-looking image of the
      borehole wall. We have demonstrated that this new side-looking tool behaves well
      with an echo time short to 0.25 ms, which ensures the richness and accuracy of
      the measurements. Such a new side-looking tool is suitable for the detection of
      unconventional reservoirs.

PMID- 30224083
TI  - Effect of transversus abdominis release on core stability: Short-term results
      from a single institution.
AB  - INTRODUCTION: Transversus abdominis release is an increasingly used procedure in
      complex abdominal wall reconstruction. The transversus abdominis muscle is a
      primary stabilizer of the spine, yet little is known regarding the effect of
      transversus abdominis release on core stability, back pain, or hernia-specific
      quality of life. The purpose of our study was to investigate the effect of
      complex abdominal wall reconstruction using transversus abdominis release on
      patient quality of life and core stability function. METHODS: All patients
      undergoing complex abdominal wall reconstruction requiring transversus abdominis
      release from June 2016 through October 2016 at our institution were eligible for
      study inclusion. Back and hernia quality-of-life measures, including the Quebec
      Back Pain Scale and the Hernia Quality of Life Survey (HerQLes), in addition to
      patient core stability, as measured using the prone test and the Sahrmann Core
      Stability Test, were collected at the preoperative evaluation and at 6 months
      after surgery. Student's t test was used to determine the effect of complex
      abdominal wall reconstruction on quality of life and core stability. RESULTS:
      Twenty-one patients completed the preoperative and 6-month postoperative
      evaluations. Back pain scores significantly improved postoperatively overall and
      in each of the 6 subcategories measured using the Quebec Back Pain Scale (P =
      .001). There was also a statistically significant improvement in abdominal wall
      function as reflected by Hernia Quality of Life Survey scores (P < .001). There
      was no statistically significant difference in core stability as reflected in the
      average prone score (P = .6) or the Sahrmann Core Stability Test average score (P
      = .4). CONCLUSION: Abdominal wall reconstruction with transversus abdominis
      release leads to improved back pain and hernia quality of life and does not
      appear to negatively affect core stability in the short term.

PMID- 30224084
TI  - Ethical considerations in the use of Pernkopf's Atlas of Anatomy: A surgical case
      study.
AB  - The use of Eduard Pernkopf's anatomic atlas presents ethical challenges for
      modern surgery concerning the use of data resulting from abusive scientific work.
      In the 1980s and 1990s, historic investigations revealed that Pernkopf was an
      active National Socialist (Nazi) functionary at the University of Vienna and that
      among the bodies depicted in the atlas were those of Nazi victims. Since then,
      discussions persist concerning the ethicality of the continued use of the atlas,
      because some surgeons still rely on information from this anatomic resource for
      procedural planning. The ethical implications relevant to the use of this atlas
      in the care of surgical patients have not been discussed in detail. Based on a
      recapitulation of the main arguments from the historic controversy surrounding
      the use of Pernkopf's atlas, this study presents an actual patient case to
      illustrate some of the ethical considerations relevant to the decision of whether
      to use the atlas in surgery. This investigation aims to provide a historic and
      ethical framework for questions concerning the use of the Pernkopf atlas in the
      management of anatomically complex and difficult surgical cases, with special
      attention to implications for medical ethics drawn from Jewish law.

PMID- 30224085
TI  - Community bioirrigation potential (BIPc), an index to quantify the potential for
      solute exchange at the sediment-water interface.
AB  - BIOIRRIGATION: the animal-induced exchange of solutes between pore water and
      overlying water - is a key process in sediments with profound implications for
      biogeochemical processes such as nutrient cycling and organic matter regeneration
      at the sediment water interface. There is an urgent need to understand how a
      changing environment will affect the irrigation activity of macrofauna and vice
      versa. A shift in species composition (e.g. from deep burrowing species to
      smaller, more opportunistic and shallow burrowing species) will have large
      effects on bioirrigation and thus on ecosystem function (such as benthic pelagic
      coupling). Considering the difficulties to determine area-covering rates of
      bioirrigation (e.g. in terms tracer-based fluxes) and the complexity of
      interactions of multiple species in the community that prohibit a direct measure
      of bioirrigation attributable to each species, a mechanistically-based approach
      is needed to predict relative intensities of bioirrigation activity based on the
      fundamental functional traits. We propose a conceptual framework to develop an
      index of bioirrigation that takes into account the biological mechanisms of
      bioirrigation and provides a simplified, yet functionally based approach to
      quantify the bioirrigation potential of benthic communities. We developed the
      community bioirrigation potential (BIPc) that provides a biomass- and abundance
      weighted scoring system considering functional traits related to pore water and
      solute exchange. It may be used as a supplement to established methods to assess
      the function of marine soft sediments related bioirrigation. In analogy to the
      particle-related community bioturbation potential of Solan et al. (2004), context
      dependent organismal traits that affect ventilation and bioirrigation (feeding
      type, morphology of burrows, and burrowing depth) are combined with the data on
      abundance and biomass of the respective species. These are subsequently summed up
      to a community bioirrigation potential (BIPc). This review considers ecological
      traits relevant for bioirrigation and their classification into a bioirrigation
      index. Furthermore the necessary simplifications in the index (e.g. limiting its
      applicability to interfacial nutrient fluxes) are discussed. We also provide a
      working example from the southwestern Baltic Sea to illustrate the practical
      application of the index and a compilation of key species related to this area
      containing their classification into the considered bioirrigation traits.

PMID- 30224086
TI  - Forecast climate change conditions sustain growth and physiology but hamper
      reproduction in range-margin populations of a foundation rockweed species.
AB  - Intensifying environmental changes due to climate change affect marine species
      worldwide. Herein, we experimentally tested if the combination of forecasted
      warming and hyposalinity adversely affected growth, receptacle formation, and
      photosynthesis of three marginal populations of the brown alga Fucus from the
      northern Baltic Sea. Growth was not impaired by the projected consequences of
      climate change but genotypes varied in their responses, suggesting existence of
      genetic variation in phenotypic plasticity. Climate change further prevented
      receptacle formation, implying that Fucus fail to reproduce sexually.
      Photosynthesis was not affected by climate change but varied among populations.
      Our results show that Fucus populations photosynthesized, grew, and survived well
      under the projected climate change but their sexual reproduction ceased. This
      suggests that the marginal populations tested herein are resilient to future
      conditions but only if asexual reproduction enables them to proliferate.

PMID- 30224087
TI  - Phonological working memory in developmental stuttering: Potential insights from
      the neurobiology of language and cognition.
AB  - The current review examines how neurobiological models of language and cognition
      could shed light on the role of phonological working memory (PWM) in
      developmental stuttering (DS). Toward that aim, we review Baddeley's influential
      multicomponent model of PWM and evidence for load-dependent differences between
      children and adults who stutter and typically fluent speakers in nonword
      repetition and dual-task paradigms. We suggest that, while nonword repetition and
      dual-task findings implicate processes related to PWM, it is unclear from
      behavioral studies alone what mechanisms are involved. To address how PWM could
      be related to speech output in DS, a third section reviews neurobiological models
      of language proposing that PWM is an emergent property of cyclic sensory and
      motor buffers in the dorsal stream critical for speech production. We propose
      that anomalous sensorimotor timing could potentially interrupt both fluent speech
      in DS and the emergent properties of PWM. To further address the role of
      attention and executive function in PWM and DS, we also review neurobiological
      models proposing that prefrontal cortex (PFC) and basal ganglia (BG) function to
      facilitate working memory under distracting conditions and neuroimaging evidence
      implicating the PFC and BG in stuttering. Finally, we argue that cognitive
      behavioral differences in nonword repetition and dual-tasks are consistent with
      the involvement of neurocognitive networks related to executive function and
      sensorimotor integration in PWM. We suggest progress in understanding the
      relationship between stuttering and PWM may be accomplished using high-temporal
      resolution electromagnetic experimental approaches.

PMID- 30224088
TI  - Transcranial Doppler Ultrasonography Provides Insights into Neurovascular Changes
      in Children with Cerebral Malaria.
AB  - OBJECTIVE: To evaluate neurovascular changes in pediatric patients with cerebral
      malaria. STUDY DESIGN: African children with cerebral malaria were enrolled and
      underwent daily transcranial Doppler ultrasound (TCD) examinations through
      hospital day 8, discharge, or death. Neurologic outcomes were assessed 2 weeks
      after enrollment. RESULTS: In total, 160 children with cerebral malaria and 155
      comparison patients were included. In patients with cerebral malaria, TCD flow
      changes characterized as hyperemia were seen in 42 (26%), low flow in 46 (28%),
      microvascular obstruction in 35 (22%), cerebral vasospasm in 21 (13%), and
      isolated posterior hyperemia in 7 (4%). Most had a single neurovascular phenotype
      observed throughout participation. Among comparison patients, 76% had normal TCD
      findings (P < .001). Impaired autoregulation was present in 80% of cases
      (transient hyperemic response ratio 1.01 +/- 0.03) but improved through day 4
      (1.1 +/- 0.02, P = .014). Overall mortality was 24% (n = 39). Neurologic deficits
      were evident in 21% of survivors. Children meeting criteria for vasospasm were
      most likely to survive with sequelae, and children meeting criteria for low flow
      were most likely to die. Autoregulation was better in children with a normal
      neurologic outcome (1.09, 95% CI 1.06-1.12) than in others (0.98, 95% CI 0.95-1)
      (P <= .001). CONCLUSIONS: Several distinct changes in TCD measurements were
      identified in children with cerebral malaria that permitted phenotypic grouping.
      Groups had distinct associations with neurologic outcomes. Validation of
      pathogenic mechanisms associated with each phenotype may aid in developing TCD as
      a portable, easy-to-use tool to help guide targeted adjunctive therapy in
      cerebral malaria aimed at causative mechanisms of injury on an individual level.

PMID- 30224089
TI  - The Extended Genotype: Microbially Mediated Olfactory Communication.
AB  - Microbes are now known to influence inter- and intraspecific olfactory signaling
      systems. They do so by producing metabolites that function as odorants. A unique
      attribute of such odorants is that they arise as a product of microbial-host
      interactions. These interactions need not be mutualistic, and indeed can be
      antagonistic. We develop an integrated ecoevolutionary model to explore
      microbially mediated olfactory communication and a process model that illustrates
      the various ways that microbial products might contribute to odorants. This novel
      approach generates testable predictions, including that selection to incorporate
      microbial products should be a common feature of infochemicals that communicate
      identity but not those that communicate fitness or quality. Microbes extend an
      individual's genotype, but also enhance vulnerability to environmental change.

PMID- 30224090
TI  - 3-D physiomimetic extracellular matrix hydrogels provide a supportive
      microenvironment for rodent and human islet culture.
AB  - Organ-on-a-chip platforms serve as cost-efficient testbeds for screening
      pharmaceutical agents, mimicking natural physiology, and studying disease. In the
      field of diabetes, the development of an islet-on-a-chip platform would have
      broad implications in understanding disease pathology and discovering potential
      therapies. Islet microphysiological systems are limited, however, by their poor
      cell survival and function in culture. A key factor that has been implicated in
      this decline is the disruption of islet-matrix interactions following isolation.
      Herein, we sought to recapitulate the in vivo peri-islet niche using
      decellularized extracellular matrix (ECM) hydrogels. Sourcing from porcine
      bladder, lung, and pancreas tissues, 3-D ECM hydrogels were generated,
      characterized, and validated using both rodent and human pancreatic islets.
      Optimized decellularization protocols resulted in hydrogels with distinctive
      viscoelastic properties that correlated to their matrix composition. The in situ
      3-D encapsulation of human or rat islets within ECM hydrogels resulted in
      improved functional stability over standard culture conditions. Islet composition
      and morphology were also altered, with enhanced retention of islet-resident
      endothelial cells and the formation of cord-like structures or sprouts emerging
      from the islet spheroid. These supportive 3-D physiomimetic ECM hydrogels can be
      leveraged within microfluidic platforms for the long-term culture of islets.

PMID- 30224092
TI  - When does absence of evidence constitute evidence of absence?
AB  - Negative forensic evidence can be defined as the failure to find a trace after
      looking for it. Such evidence is often dismissed by referring to the aphorism
      "absence of evidence is not evidence of absence." However, this reasoning can be
      misleading in the context of forensic science. This commentary is designed to
      help forensic scientists understand the probative value of negative forensic
      evidence.

PMID- 30224093
TI  - [Multimodal imaging approach to an embolus in a central retinal artery
      occlusion].

PMID- 30224094
TI  - [Upside-down hypopyon].

PMID- 30224095
TI  - [Angioid streaks in a 33-year-old man with beta-Thalassemia].

PMID- 30224091
TI  - Development of the human prostate.
AB  - This paper provides a detailed compilation of human prostatic development that
      includes human fetal prostatic gross anatomy, histology, and ontogeny of selected
      epithelial and mesenchymal differentiation markers and signaling molecules
      throughout the stages of human prostatic development: (a) pre-bud urogenital
      sinus (UGS), (b) emergence of solid prostatic epithelial buds from urogenital
      sinus epithelium (UGE), (c) bud elongation and branching, (d) canalization of the
      solid epithelial cords, (e) differentiation of luminal and basal epithelial
      cells, and (f) secretory cytodifferentiation. Additionally, we describe the use
      of xenografts to assess the actions of androgens and estrogens on human fetal
      prostatic development. In this regard, we report a new model of de novo DHT
      induction of prostatic development from xenografts of human fetal female
      urethras, which emphasizes the utility of the xenograft approach for
      investigation of initiation of human prostatic development. These studies raise
      the possibility of molecular mechanistic studies on human prostatic development
      through the use of tissue recombinants composed of mutant mouse UGM combined with
      human fetal prostatic epithelium. Our compilation of human prostatic
      developmental processes is likely to advance our understanding of the
      pathogenesis of benign prostatic hyperplasia and prostate cancer as the
      neoformation of ductal-acinar architecture during normal development is shared
      during the pathogenesis of benign prostatic hyperplasia and prostate cancer.

PMID- 30224096
TI  - [Retinal detachment surgery: Evaluation of the anatomical success and functional
      outcomes in a consecutive series of patients operated between 2011 and 2014 at
      Nantes University Medical Center].
AB  - OBJECTIVE: Evaluate the anatomical and functional outcomes of retinal detachment
      (RD) surgery from January 2011 to November 2014. MATERIALS AND METHODS: We
      conducted a retrospective study of 182 eyes of 175 patients with a minimum follow
      up of 6 months, operated for RD at Nantes University Medical Center. It consists
      of 56 simple RDs and 126 complex RDs treated in first intention by Scleral
      Buckling (SB), vitrectomy or combined surgery. The analysis is based on anatomic
      reattachment at the end of a follow-up of at least 6 months after the first
      surgery and the progression of the best corrected visual acuity (BCVA). RESULTS:
      One hundred and seventy-two vitrectomies, 15 SB and 5 combined surgeries
      (vitrectomy+SB) were performed. The overall anatomical success rate after a
      single operation was 131 eyes (72 %). It increased to 163 eyes (90 %) at the end
      of the follow-up. Depending on the type of RD, anatomic success at 6 months after
      surgery was achieved for 47 simple RDs (84 %) and 84 complex RDs (67 %). At the
      end of the follow-up, after one or more operations, these rates increased to 53
      simple RDs (95 %) and 110 complex RDs (87 %). For all RDs with an anatomically
      successful result, we observed a visual improvement>=2 lines in 45 % of cases and
      a postoperative BCVA>=5/10 in 40 % of cases. CONCLUSION: This study confirms the
      evolution toward vitrectomy surgery for retinal detachment. It finds anatomical
      and functional results consistent with the literature, with a percentage of
      approximately 5 % of RDs still not reattached in spite of several operations.

PMID- 30224097
TI  - The first world swimming championships of roseobacters-Phylogenomic insights into
      an exceptional motility phenotype.
AB  - Many marine Alphaproteobacteria of the Roseobacter group show a characteristic
      swim-or-stick lifestyle, for which motility is a crucial trait. Three
      phylogenetically distinct flagellar gene clusters (FGCs) have been identified in
      Rhodobacteraceae that have been named fla1, fla2 and fla3 according to their
      relative abundance. In addition to the flagellar-dependent swimming and swarming
      motility, pilus-dependent twitching mediates bacterial locomotion. Furthermore,
      filament independent modes of motility, namely gliding and sliding, have been
      described for various microorganisms. However, no mode of motility other than
      swimming has so far been described for roseobacters. In the present study, we
      investigated motility, distribution of flagellar systems and the phylogeny of 120
      genome-sequenced Rhodobacteraceae. The phylogenetically broad taxon sampling that
      included 114 type strains revealed the presence of at least ten distinct clades
      that were statistically well supported. The investigation of the actual
      physiological capacity for swimming motility on soft agar plates showed that only
      about half of the 120 tested strains were motile under the tested conditions.
      Seven strains developed a conspicuous dendritic motility phenotype that was
      reminiscent of the swarming motility in Pseudomonas aeruginosa. The observed
      dendritic motility in two strains (i.e. Sulfitobacter pseudonitzschiae DSM 26842
      and Roseovarius pacificus DSM 29589) was particularly surprising because they did
      not harbor any genes of the FGC. Accordingly, it was concluded that this form of
      dendritic motility was independent of a flagellum. A comparative genomics
      approach allowed a remarkable number of pilus-related candidate genes to be
      identified for this novel type of motility in Rhodobacteraceae.

PMID- 30224098
TI  - [Bone epithelioid hemangioendotheliom].
AB  - INTRODUCTION: Epithelioid hemagioendothelioma (HHE) is a rare mesenchymal tumor
      of vascular origin and epithelial appearance, which develops like angiosarcoma to
      mimic endothelial cells. According to the literature, its prognosis is variable
      and remains unpredictable. CASE REPORT: We report a 72-year-old man who presented
      with an inflammatory pain in the left lower limb. Several osteolytic lesions
      involving the knee, the upper third of the tibia, the medial malleolus and the
      left calcaneus were identified. The diagnosis HHE was obtained by histological
      examination of a bone sample. The patient died after 5 months, despite taxol
      chemotherapy. CONCLUSION: No therapeutic behavior is standardized in this
      uncommon type of cancer.

PMID- 30224099
TI  - Mortality During Total Knee Periprosthetic Joint Infection.
AB  - BACKGROUND: Periprosthetic joint infections (PJIs) are fraught with multiple
      complications including poor patient-reported outcomes, disability, reinfection,
      disarticulation, and even death. We sought to perform a systematic review asking
      the question: (1) What is the mortality rate of a PJI of the knee undergoing 2
      stage revision for infection? (2) Has this rate improved over time? (3) How does
      this compare to a normal cohort of individuals? METHODS: We performed a database
      search in MEDLINE/EMBASE, PubMed, and all relevant reference studies using the
      following keywords: "periprosthetic joint infection," "mortality rates," "total
      knee arthroplasty," and "outcomes after two stage revision." Two hundred forty
      two relevant studies and citations were identified, and 14 studies were extracted
      and included in the review. RESULTS: A total of 20,719 patients underwent 2-stage
      revision for total knee PJI. Average age was 66 years. Mean mortality percentage
      reported was 14.4% (1.7%-34.0%) with average follow-up 3.8 years (0.25-9 years).
      One-year mortality rate was 4.33% (3.14%-5.51%) after total knee PJI with an
      increase of 3.13% per year mortality thereafter (r = 0.76 [0.49, 0.90], P <
      .001). Five-year mortality was 21.64%. When comparing the national age-adjusted
      mortality (Actuarial Life Table) and the reported 1-year mortality risk in this
      meta-analysis, the risk of death after total knee PJI is significantly increased,
      with an odds ratio of 3.05 (95% confidence interval, 2.69-3.44; P < .001).
      CONCLUSION: The mortality rate after 2-stage total knee revision for infection is
      very high. When counseling a patient regarding complications of this disease,
      death should be discussed.

PMID- 30224100
TI  - Septic Revision Total Knee Arthroplasty: Treatment of Metaphyseal Bone Defects
      Using Metaphyseal Sleeves.
AB  - BACKGROUND: Bone loss is a severe problem in septic revision total knee
      arthroplasty (RTKA). The use of porous coated metaphyseal sleeves is a promising
      treatment option for metaphyseal bone defects. The currently published midterm
      results remain limited and no study has been focused exclusively on septic cases.
      Our aim was to determine the implant survivorship (with special focus on
      osseointegration) and the clinical and radiological midterm outcome of
      metaphyseal sleeve fixation in septic RTKA surgery (minimum follow-up of 2
      years). METHODS: We performed a clinical and radiographic examination of 56
      patients with a history of prosthetic joint infection who underwent 2-stage RTKA
      with the use of porous coated metaphyseal sleeves. These examinations included
      evaluation of the American Knee Society Score, the Western Ontario and McMaster
      Universities Osteoarthritis Index, the Short Form (SF-36) Health survey as well
      as radiographic measurement to determine whether successful osseointegration had
      been achieved. RESULTS: Nine patients (16%) had to be re-revised at the time of
      follow-up (mean, 5.3 years; range, 2-11.2), all due to reinfection. We did not
      encounter any cases of aseptic loosening. The mean range of motion (92 degrees ,
      SD +/- 21 degrees ), subjective satisfaction score (7, SD +/- 2), American Knee
      Society Score (76, SD +/- 19), Western Ontario and McMaster Universities
      Osteoarthritis Index (70, SD +/- 20), SF-36 mental component summary (55, SD +/-
      14), and SF-36 physical component summary (35, SD +/- 9) have shown satisfying
      results. CONCLUSION: Metaphyseal sleeves have shown very promising midterm
      results regarding clinical scores, osseointegration, and aseptic loosening. Our
      results are the first analyzing exclusively septic indications and indicate that
      they are a reliable fixation option in all bone defect types in septic RTKA
      patients.

PMID- 30224101
TI  - Comparison of temporalis fascia and tragal cartilage grafts in type 1
      tympanoplasty in elderly patients.
AB  - OBJECTIVE: To investigate the success rates and hearing outcomes of temporalis
      fascia and tragal cartilage grafts used for type-1 tympanoplasty in the elderly
      (365 years) METHODS: The medical records of 73 elderly patients who underwent
      type-1 tympanoplasty at our center between January 2010 and June 2017 were
      retrospectively reviewed for age, gender, perforation side, presence of
      contralateral perforation, type and location of perforation, graft material
      types, preoperative and postoperative hearing levels, and length of follow-up.
      RESULTS: The graft success rate was 83.5% (61 patients) for the entire group,
      76.2% (32 patients) for the fascia group, and 93.5% (29 patients) for the
      cartilage group. The success rate for the cartilage group was significantly
      higher than that for the fascia group (P=0.048). The mean hearing gain was 12.5+/
      7.6 and 8.9+/-6.1dB in the fascia and cartilage groups, respectively, and
      postoperative ABG was 10 dB or better in 29 (69.0%) and 19 (61.3%) patients,
      respectively. The mean hearing gain was significantly higher in the fascia group
      than in the cartilage group (P=0.028), whereas the mean ABG was significantly
      higher in the cartilage group than in the fascia group (P=0.009). The functional
      success rates were similar in both groups (P=0.490). CONCLUSION: Tympanoplasty is
      a safe and effective procedure in elderly patients with a 83.5% of graft success
      rate. Tragal cartilage may be the first choice of graft material due to its high
      success rates. The functional outcomes did not show significant differences
      between the fascia and cartilage groups.

PMID- 30224102
TI  - Expression of thioredoxin and glutaredoxin in experimental hepatocellular
      carcinoma-Relevance for prognostic and diagnostic evaluation.
AB  - Hepatocellular carcinoma (HCC), represents more than 85% of liver cancers. The
      diagnosis of HCC may be delayed due to the absence of early, sensitive and
      specific biomarkers. This study was conducted to investigate whether the
      expression of thioredoxin (Trx) and glutaredoxin (Grx) is helpful for HCC
      diagnosis in an experimental model. Twenty male albino rats were equally divided
      into two groups (HCC and control). Hepatocarcinogenesis was performed by single
      intraperitoneal (i.p) injection of 200 mg/kg of diethylnitrosamine (DENA). Two
      weeks later, 0.05% of phenobarbital (PB) was supplied in the drinking water for
      other 14 weeks. HCC was diagnosed by measuring serum alpha-fetoprotein (AFP)
      level and histopathological examination. Our results found that hepatic indices
      alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin were
      elevated but decreased total protein level. Lipid peroxidation was elevated
      through increasing hepatic content of MDA with decreased antioxidant parameters
      like hepatic SOD, CAT activities and GSH. The current study also found that Trx
      and Grx tissue genes were overexpressed in HCC group significantly, compared to
      control group. This study substantiated that increased expression of these
      enzymes may be predictive of outcomes in HCC.

PMID- 30224104
TI  - Are We Ready to Use Constrained Optimization in Health Outcomes Research?

PMID- 30224103
TI  - Application of Constrained Optimization Methods in Health Services Research:
      Report 2 of the ISPOR Optimization Methods Emerging Good Practices Task Force.
AB  - BACKGROUND: Constrained optimization methods are already widely used in health
      care to solve problems that represent traditional applications of operations
      research methods, such as choosing the optimal location for new facilities or
      making the most efficient use of operating room capacity. OBJECTIVES: In this
      paper we illustrate the potential utility of these methods for finding optimal
      solutions to problems in health care delivery and policy. To do so, we selected
      three award-winning papers in health care delivery or policy development,
      reflecting a range of optimization algorithms. Two of the three papers are
      reviewed using the ISPOR Constrained Optimization Good Practice Checklist,
      adapted from the framework presented in the initial Optimization Task Force
      Report. The first case study illustrates application of linear programming to
      determine the optimal mix of screening and vaccination strategies for the
      prevention of cervical cancer. The second case illustrates application of the
      Markov Decision Process to find the optimal strategy for treating type 2 diabetes
      patients for hypercholesterolemia using statins. The third paper (described in
      Appendix 1) is used as an educational tool. The goal is to describe the
      characteristics of a radiation therapy optimization problem and then invite the
      reader to formulate the mathematical model for solving it. This example is
      particularly interesting because it lends itself to a range of possible models,
      including linear, nonlinear, and mixed-integer programming formulations. From the
      case studies presented, we hope the reader will develop an appreciation for the
      wide range of problem types that can be addressed with constrained optimization
      methods, as well as the variety of methods available. CONCLUSIONS: Constrained
      optimization methods are informative in providing insights to decision makers
      about optimal target solutions and the magnitude of the loss of benefit or
      increased costs associated with the ultimate clinical decision or policy choice.
      Failing to identify a mathematically superior or optimal solution represents a
      missed opportunity to improve economic efficiency in the delivery of care and
      clinical outcomes for patients. The ISPOR Optimization Methods Emerging Good
      Practices Task Force's first report provided an introduction to constrained
      optimization methods to solve important clinical and health policy problems. This
      report also outlined the relationship of constrained optimization methods
      relative to traditional health economic modeling, graphically illustrated a
      simple formulation, and identified some of the major variants of constrained
      optimization models, such as linear programming, dynamic programming, integer
      programming, and stochastic programming. The second report illustrates the
      application of constrained optimization methods in health care decision making
      using three case studies. The studies focus on determining optimal screening and
      vaccination strategies for cervical cancer, optimal statin start times for
      diabetes, and an educational case to invite the reader to formulate radiation
      therapy optimization problems. These illustrate a wide range of problem types
      that can be addressed with constrained optimization methods.

PMID- 30224105
TI  - Assessing the Value of Next-Generation Sequencing Technologies: An Introduction.

PMID- 30224107
TI  - Valuation of Health and Nonhealth Outcomes from Next-Generation Sequencing:
      Approaches, Challenges, and Solutions.
AB  - BACKGROUND: Next-generation sequencing (NGS) technologies have seen variable
      adoption in the clinic. This is partly due to a lack of clinical and economic
      studies, with the latter increasingly challenged to examine patient preferences
      for health and nonhealth outcomes (e.g., false-positive rate). OBJECTIVES: To
      conduct a structured review of studies valuing patients' preference-based utility
      for NGS outcomes, to highlight identified methodological challenges, and to
      consider how studies addressed identified challenges. METHODS: We searched
      MEDLINE (PubMed), Embase (Ovid), and Web of Science for published studies
      examining outcomes from health care decisions informed by NGS. We focused our
      search on direct elicitations of preference-based utility. We reviewed included
      studies and qualitatively grouped and summarized stated challenges and solutions
      by theme. RESULTS: Eleven studies were included. Most of them (n = 6) used
      discrete choice experiments to value utility. We categorized challenges into four
      themes: 1) valuing the full range of NGS outcomes, 2) accounting for accuracy and
      uncertainty surrounding effectiveness, 3) allowing for simultaneous multiple and
      cascading risks, and 4) incorporating downstream consequences. Studies found
      strong evidence of utility for NGS information, regardless of health improvement.
      Investigators addressed challenges by simplifying complex choices, by including
      health outcomes alongside nonhealth outcomes, and by using multiple elicitation
      techniques. CONCLUSIONS: The breadth and complexity of NGS-derived information
      makes the technology a unique and challenging application for utility valuation.
      Failing to account for the utility or disutility of NGS-related nonhealth
      outcomes may lead to overinvestment or underinvestment in NGS, and so there is a
      need for research addressing unresolved challenges.

PMID- 30224106
TI  - Methodological Issues in Assessing the Economic Value of Next-Generation
      Sequencing Tests: Many Challenges and Not Enough Solutions.
AB  - BACKGROUND: Clinical use of next-generation sequencing (NGS) tests has been
      increasing, but few studies have examined their economic value. Several studies
      have noted that there are methodological challenges to conducting economic
      evaluations of NGS tests. OBJECTIVE: Our objective was to examine key
      methodological challenges for conducting economic evaluations of NGS tests,
      prioritize these challenges for future research, and identify how studies have
      attempted solutions to address these challenges. METHODS: We identified
      challenges for economic evaluations of NGS tests using prior literature and
      expert judgment of the co-authors. We used a modified Delphi assessment to
      prioritize challenges, based on importance and probability of resolution. Using a
      structured literature review and article extraction we then assessed whether
      published economic evaluations had addressed these challenges. RESULTS: We
      identified 11 challenges for conducting economic evaluations of NGS tests. The
      experts identified three challenges as the top priorities for future research:
      complex model structure, timeframe, and type of analysis and comparators used. Of
      the 15 published studies included in our literature review, four studies
      described specific solutions relevant to five of the 11 identified challenges.
      CONCLUSIONS: Major methodological challenges to economic evaluations of NGS tests
      remain to be addressed. Our results can be used to guide future research and
      inform decision-makers on how to prioritize research on the economic assessment
      of NGS tests.

PMID- 30224108
TI  - Using "Big Data" in the Cost-Effectiveness Analysis of Next-Generation Sequencing
      Technologies: Challenges and Potential Solutions.
AB  - Next-generation sequencing (NGS) is considered to be a prominent example of "big
      data" because of the quantity and complexity of data it produces and because it
      presents an opportunity to use powerful information sources that could reduce
      clinical and health economic uncertainty at a patient level. One obstacle to
      translating NGS into routine health care has been a lack of clinical trials
      evaluating NGS technologies, which could be used to populate cost-effectiveness
      analyses (CEAs). A key question is whether big data can be used to partially
      support CEAs of NGS. This question has been brought into sharp focus with the
      creation of large national sequencing initiatives. In this article we summarize
      the main methodological and practical challenges of using big data as an input
      into CEAs of NGS. Our focus is on the challenges of using large observational
      datasets and cohort studies and linking these data to the genomic information
      obtained from NGS, as is being pursued in the conduct of large genomic sequencing
      initiatives. We propose potential solutions to these key challenges. We conclude
      that the use of genomic big data to support and inform CEAs of NGS technologies
      holds great promise. Nevertheless, health economists face substantial challenges
      when using these data and must be cognizant of them before big data can be
      confidently used to produce evidence on the cost-effectiveness of NGS.

PMID- 30224109
TI  - Cost Analyses of Genomic Sequencing: Lessons Learned from the MedSeq Project.
AB  - OBJECTIVE: To summarize lessons learned while analyzing the costs of integrating
      whole genome sequencing into the care of cardiology and primary care patients in
      the MedSeq Project by conducting the first randomized controlled trial of whole
      genome sequencing in general and specialty medicine. METHODS: Case study that
      describes key methodological and data challenges that were encountered or are
      likely to emerge in future work, describes the pros and cons of approaches
      considered by the study team, and summarizes the solutions that were implemented.
      RESULTS: Major methodological challenges included defining whole genome
      sequencing, structuring an appropriate comparator, measuring downstream costs,
      and examining clinical outcomes. Discussions about solutions addressed conceptual
      and practical issues that arose because of definitions and analyses around the
      cost of genomic sequencing in trial-based studies. CONCLUSIONS: The MedSeq
      Project provides an instructive example of how to conduct a cost analysis of
      whole genome sequencing that feasibly incorporates best practices while being
      sensitive to the varied applications and diversity of results it may produce.
      Findings provide guidance for researchers to consider when conducting or
      analyzing economic analyses of whole genome sequencing and other next-generation
      sequencing tests, particularly regarding costs.

PMID- 30224110
TI  - From the Past to the Present: Insurer Coverage Frameworks for Next-Generation
      Tumor Sequencing.
AB  - Next-generation sequencing promises major advancements in precision medicine but
      faces considerable challenges with insurance coverage. These challenges are
      especially important to address in oncology in which next-generation tumor
      sequencing (NGTS) holds a particular promise, guiding the use of life-saving or
      life-prolonging therapies. Payers' coverage decision making on NGTS is
      challenging because this revolutionary technology pushes the very boundaries of
      the underlying framework used in coverage decisions. Some experts have called for
      the adaptation of the coverage framework to make it better equipped for assessing
      NGTS. Medicare's recent decision to cover NGTS makes this topic particularly
      urgent to examine. In this article, we discussed the previously proposed
      approaches for adaptation of the NGTS coverage framework, highlighted their
      innovations, and outlined remaining gaps in their ability to assess the features
      of NGTS. We then compared the three approaches with Medicare's national coverage
      determination for NGTS and discussed its implications for US private payers as
      well as for other technologies and clinical areas. We focused on US payers
      because analyses of coverage approaches and policies in the large and complex US
      health care system may inform similar efforts in other countries. We concluded
      that further adaptation of the coverage framework will facilitate a better suited
      assessment of NGTS and future genomics innovations.

PMID- 30224111
TI  - Physicians' Decision Making on Adoption of New Technologies and Role of Coverage
      with Evidence Development: A Qualitative Study.
AB  - OBJECTIVES: To foster value-based pricing and coverage with evidence development
      in Germany, certain new diagnostic and treatment methods have been subject to a
      benefit assessment since 2016 to determine their reimbursement. Although this is
      a paradigm shift, the German approach is limited to some few specific
      technologies for which reimbursement is requested. As physicians encounter this
      regulatory instrument, the aim of the study was to understand physicians'
      decision making regarding the adoption of new medical technologies and to
      identify their perspectives on the evidence base and financing with additional
      reimbursement systems. METHODS: From April to August 2017, semistructured
      interviews with chief and senior physicians of vascular surgery and cardiology in
      inpatient care in Germany were conducted (N = 23). The interviews were carried
      out by one researcher in one-to-one appointments or via telephone. Data were
      analyzed inductively to identify factors and generate thematic categories using
      qualitative content analysis. RESULTS: We identified 52 factors in eight
      categories influencing physicians' adoption of new technologies. The evidence
      base for new technologies was criticized (e.g., lack of available studies).
      Physicians' knowledge of the regulation of market approval and innovation
      payments varied. They recommended the utilization of new technologies in certain
      specialist centers and the facilitation of observational studies. CONCLUSIONS:
      Physicians saw the need for the new approach and supported its aim. However, its
      design and implementation appeared to be questionable from their medical
      perspective. The provision of summarized information on the benefit of
      technologies might be a possibility to assist physicians' decision making.

PMID- 30224112
TI  - On the Value of the Umbilical Cord Blood Supply.
AB  - BACKGROUND: Several public cord blood banks are struggling financially, and the
      question remains as to whether additional allocations of funds to them are
      justified. OBJECTIVES: To estimate the social benefits of public cord blood bank
      inventory net of cord blood banks' operational costs. METHODS: We used publicly
      available data from the Health Resources and Service Administration on the number
      of annual cord blood transplants as well as the patient age distribution in 2010,
      and the survival estimates between 2008 and 2012 for the several diseases treated
      by cord blood transplantation. Data on aggregate annual costs to the cord blood
      industry for recruitment, processing, and storage were obtained from published
      work. We used estimated increases in life expectancy due to treatment using
      umbilical cord blood and value for life-years gained to estimate the social
      benefits of the public cord blood inventory annually. RESULTS: We found that the
      annual social benefits of between $500 million and $1.5 billion outweigh the
      current operational annual costs of running cord blood banks of $60 to $70
      million by a significant margin. CONCLUSIONS: We estimated that the annual social
      benefit of having a cord blood system far outweighs its costs, by more than an
      order of magnitude. Thus, the social benefits of maintaining the US public cord
      blood banking system at the present time far outweigh the costs of collecting,
      storing, and distributing cord blood. This suggests that there is a potential
      justification for government intervention to align social benefits and costs.
      Nevertheless, simple fixes may produce unintended consequences, and so a careful
      design for subsidies is needed.

PMID- 30224113
TI  - Cost Sharing of Disease-Modifying Treatments (DMTs) as Policy Lever to Improve
      DMTs' Access in Multiple Sclerosis.
AB  - OBJECTIVES: To understand the nonlinear relationship between out-of-pocket (OOP)
      payments and disease-modifying treatment (DMT) use and adherence, primarily to
      pinpoint the threshold at which the use of DMTs becomes price sensitive. METHODS:
      Individuals with more than two multiple sclerosis (MS) diagnoses (International
      Classification of Diseases, Ninth Revision code 340) were identified from the
      MarketScan database (2006-2009). Heterogeneity in treatment was normalized by
      calculating an annual OOP payment as the average OOP payment for purchasing a
      fixed basket of DMTs at the insurance plan level. A local linear regression with
      a model-based recursive partitioning algorithm was applied to explore the
      relationship between OOP and consequently lower DMT use and adherence as measured
      by days covered by DMT. RESULTS: We identified the inflection points in annual
      OOP payments as $442 for DMT use and $890 for DMT adherence. For patients with
      annual OOP payments of more than $442, a $100-increase in OOP payment was
      associated with a decline of 0.6% in DMT use; for annual OOP payments of more
      than $890, a $100-increase in OOP payment was associated with two fewer days of
      DMT treatments. CONCLUSIONS: Although the use of DMTs and DMT adherence appeared
      unassociated with OOP payment below $442 and $890, respectively, an excessive OOP
      payment was a barrier to DMT access. This information can inform maximum monthly
      and yearly payment caps when designing valued-based insurance plans.

PMID- 30224114
TI  - Minimally Important Difference of the EQ-5D-5L Index Score in Adults with Type 2
      Diabetes.
AB  - BACKGROUND: The EuroQol five-dimensional questionnaire (EQ-5D) is a generic
      preference-based measure of health-related quality of life, and several studies
      have made attempts to estimate the minimally important difference (MID) for the
      EQ-5D index score. OBJECTIVES: To estimate the MID of the five-level EQ-5D (EQ-5D
      5L) index score in a population-based sample of adults with type 2 diabetes and
      to explore whether the MID estimate varies by baseline index score and the
      direction of change in health status. METHODS: We used longitudinal survey data
      of adults with type 2 diabetes in Alberta, Canada. The EQ-5D-5L MID was estimated
      first by the instrument-defined approach, which used the difference between the
      baseline index scores and the index scores of simulated single-level transitions,
      and then by the anchor-based approach, which categorized 1-year changes in
      depressive symptoms, diabetes-related distress, as well as physical and mental
      health functioning into no change, small change, and large change groups, wherein
      the MID was estimated as the average change in index score of the small change
      group. RESULTS: Using the instrument-defined approach, MID estimates were 0.043,
      0.040, and 0.045, whereas anchor-based MID estimates were 0.042, 0.034, and 0.049
      for all change, improvement, and deterioration, respectively. Larger MID
      estimates were observed for lower baseline index scores and for deterioration in
      health status. CONCLUSIONS: MID estimates of the EQ-5D-5L index score were
      consistent between instrument-defined and anchor-based approaches and ranged
      between 0.03 and 0.05. Estimates varied by baseline index score and the direction
      of change, with similar results for patient subgroups.

PMID- 30224115
TI  - Development and Validation of an Algorithm for Identifying Patients with
      Hemophilia A in an Administrative Claims Database.
AB  - BACKGROUND: The accuracy with which hemophilia A can be identified in claims
      databases is unknown. OBJECTIVE: Develop and validate an algorithm using
      predictive modeling supported by machine learning to identify patients with
      hemophilia A in an administrative claims database. METHODS: We first created a
      screening algorithm using medical and pharmacy claims to identify potential
      hemophilia A patients in the US HealthCore Integrated Research Database between
      January 1, 2006 and April 30, 2015. Medical records for a random sample of
      patients were reviewed to confirm case status. In this validation sample, we used
      lasso logistic regression with cross-validation to select covariates in claims
      data and develop a predictive model to estimate the probability of being a
      confirmed hemophilia A case. RESULTS: The screening algorithm identified 2,252
      patients and we reviewed medical records for 400 of these patients. The screening
      algorithm had a positive predictive value (PPV) of 65%. The predictive model
      identified 18 predictors of being a hemophilia A case or noncase. The strongest
      predictors of case status included male sex, factor VIII therapy, office visits
      for hemophilia A, and hospitalizations for hemophilia A. The strongest predictors
      of noncase status included hospitalizations for reasons other than hemophilia A
      and factor VIIa therapy. A probability threshold of >=0.6 resulted in a PPV of
      94.7% (95% CI: 92.0-97.5) and sensitivity of 94.4% (95% CI: 91.5-97.2).
      CONCLUSIONS: We developed and validated an algorithm to identify hemophilia A
      cases in an administrative claims database with high sensitivity and high PPV.

PMID- 30224116
TI  - Evaluation of the Measurement Properties of Four Performance Outcome Measures in
      Patients with Elective Hip Replacements, Elective Knee Replacements, or Hip
      Fractures.
AB  - OBJECTIVES: To evaluate the measurement properties of four performance outcome
      (PerfO) measures (timed up and go, four-step stair climb, long stair climb, and
      repeated chair stand) in three patient populations(elective total hip replacement
      [eTHR], elective total knee replacement [eTKR], and hip fracture [HF]). METHODS:
      A cross-sectional and longitudinal design was used to assess the PerfO
      measurement properties using the US Food and Drug Administration guidance for
      industry around patient-reported outcome measures to support labeling claims.
      Patient-reported outcome measures and patient- and clinician-reported global
      concept items were completed along with four PerfO measures at visit 1 and two
      follow-up visits. Measurement properties assessed included reliability, construct
      validity, ability to detect change, and estimates of meaningful change. RESULTS:
      A total of 280 patients (100 eTHR, 105 eTKR, and 75 HF) were recruited, with most
      (n = 276) providing data at visit 1. Most of the patients were female (64%) and
      retired (64%), and had at least one comorbidity (91%). Inter-rater and test
      retest reliability ranged from good to excellent (0.73 <= intraclass correlation
      coefficient <= 0.95) for each PerfO measure. Known-groups validity was
      demonstrated for all PerfO measures, with those reporting less pain better
      physical functioning and those who did not use an assistive device having quicker
      mean completion times. Construct validity and ability to detect change were
      demonstrated and estimates of meaningful change derived. CONCLUSIONS: This study
      found the measurement properties of four PerfO measures in samples of patients
      with eTHR, eTKR, and HF to be supported for consideration of future use, and
      provided estimates for interpretation of change.

PMID- 30224117
TI  - Evaluating the Content Validity of Four Performance Outcome Measures in Patients
      with Elective Hip Replacements and Hip Fractures.
AB  - OBJECTIVES: To assess the content validity of performance outcome (PerfO)
      measures for use with patients undergoing hip fracture (HF) surgery and elective
      total hip replacement (eTHR). METHODS: This study was a substudy of a broader
      evaluation of measurement properties of PerfO measures. The PerfO measures
      assessed were timed up and go (TUG), four-step stair climb (4SC), long stair
      climb (LSC), and repeated chair stand (RCS). For this substudy, HF and eTHR
      participants were interviewed to evaluate the relevance and difficulty of each
      PerfO measure. Qualitative analysis was conducted on interview transcripts, and
      summaries of coded data were produced to assess saturation. RESULTS: All 18 HF
      participants related the PerfO measures (TUG, 4SC, and RSC) to activities they
      completed in daily life, with slight variations in some specific aspects. For the
      eight eTHR participants, the correspondence between the PerfO measures (TUG, 4SC,
      and LSC) and activities in daily life varied: all participants saw similarity in
      the movements for the TUG; most undertook short stair climbs in daily life, but
      most did not regularly undertake LSC in daily life. Nevertheless, all HF and eTHR
      participants reported that the PerfO measures were relevant and had a level of
      difficulty similar to daily activities. CONCLUSIONS: This study contributes novel
      methods that adapt US regulatory guidance for patient-reported outcome measures
      to the evaluation of PerfO measures. A structured approach was used to explore
      specific details of each measure and correspondence to everyday life. This study
      demonstrates how content validity of PerfO measures can be meaningfully assessed.

PMID- 30224119
TI  - CORRECTION.

PMID- 30224126
TI  - P 106 - Intra- and inter-operator reliability of a novel hand protocol during
      grip movement in healthy subjects.

PMID- 30224118
TI  - Quality-Adjusted Life-Years without Constant Proportionality.
AB  - BACKGROUND: A quality-adjusted life-year is a common unit of measurement in
      health valuation. Under its constant proportionality assumption, the value of a
      quality-adjusted life span is defined as the product of preference weight and
      life span. OBJECTIVES: To empirically identify an alternative functional
      relationship between life span and value by relaxing the constant proportionality
      assumption. METHODS: Using an online survey, 5367 respondents completed 30 to 40
      paired comparisons where each involved a choice between two health outcomes: one
      with a longer life span and health problems (five-level EuroQol five-dimensional
      questionnaire) and the other with a shorter life span and no problems (time trade
      off pair). Using 2670 pairs, a saturated model with indicator variables for 27
      life spans and 90 health problems of varying duration and severity was estimated
      by maximum likelihood. Its coefficients empirically illustrate the relationship
      between life span and value on a quality-adjusted life-year scale. RESULTS: The
      results reject constant proportionality (P < 0.01) and support the use of a power
      function to describe the relationship between life span and value, namely, value
      = preference weight * life spanbeta. The estimate of power (beta = 0.415; 95%
      confidence interval 0.41-0.42) appears to depend on whether life span was
      expressed in a temporal unit of days (0.403), weeks (0.509), months (0.541), or
      years (0.654). CONCLUSIONS: Raising life span to a power less than 1 implies
      decreasing marginal value of life span and greatly improved model fit, and
      confirms previous violations of proportionality. This power function may replace
      conventional assumptions in health valuation studies. Nevertheless, governmental
      agencies may favor a longer time horizon than that of the general population.

PMID- 30224127
TI  - PTR-MS and GC-MS as complementary techniques for analysis of volatiles: A
      tutorial review.
AB  - This tutorial review is a critical commentary on the combined use of two
      instrumental analytical techniques, namely GC-MS and PTR-MS. The first mention of
      such an analytical approach likely appeared after the year 2000 and despite many
      advantages, it has not been applied very often. Therefore, the aim of this
      article is to elaborate on the concept of their combined use and to provide a
      curse tutorial for those considering taking such an approach. The issue of
      complementarity was raised in a broad sense of this term. Special emphasis was
      placed on indicating the possibilities of complementary utilization of GC-MS and
      PTR-MS and presenting the advantages and disadvantages as well as the current
      application of these techniques when used together.

PMID- 30224128
TI  - Graphene oxide aggregate-assisted LDI-MS for the direct analysis of
      triacylglycerol in complex biological samples.
AB  - Knowledge of blood triacylglycerol (TAG) species is essential to clarify the
      physiological functions of individual TAG molecules and also to develop potential
      biomarkers for related diseases. Commonly, lipid samples prepared by organic
      liquid-liquid extraction contain complex components, thus cannot be directly
      characterized by mass spectrometry (MS) and often require an additional
      purification step. Here, we described a laser desorption ionization - mass
      spectrometry (LDI-MS) method that utilized aggregated graphene oxide (AGO) as
      both lipid extractant and MS matrix (AGOLDI-MS), to characterize and quantify
      plasma TAG species without the use of harmful solvent or complex separation step.
      We first designed and synthesized the AGO material with a multi-layered sheet
      structure, which could efficiently break up the structure of lipoproteins, and
      extract plasma TAGs as solid-phase extraction material. Furthermore, in AGOLDI-MS
      procedure, the AGO could directly act as matrix and selectively produce the MS
      signals of TAGs without the interferences of phospholipids, which was hardly
      achieved by using the routine LDI-MS method based on liquid-liquid extraction and
      small molecular matrix. We confirmed the suitability of AGOLDI-MS as
      characterization and quantitative tool for TAG species through studying the
      analysis performances in TAG standards and real plasma samples. To establish
      potential utility of our method, we characterized 42 human plasmas from healthy
      and hyperlipemic donators, indicating that the AGOLDI-MS could not only generate
      comparable quantitative results of total TAGs to current clinical technology, but
      also monitor the changes of TAG species between different sample groups. This
      approach could further characterize the compositions of the fatty acid moieties
      in even low abundant TAGs by the assistance of tandem MS-MS. This concise,
      specific, and high-throughput approach will facilitate the rapid and precise
      characterizations of plasma TAGs, and make the MS approach for TAGs more
      adaptable for clinical uses.

PMID- 30224129
TI  - Rapid detection of taste and odor compounds in water using the newly invented
      chemi-ionization technique coupled with time-of-flight mass spectrometry.
AB  - Taste and odor (T&O) compounds are widespread in water environments and have
      attracted considerable public attention. Nowadays, the standard detections of
      these chemicals rely mainly on off-line methods such as GC-MS or evaluation by
      trained analysts' senses. In this study, we report a method for the rapid
      detection of T&O compounds in water by exploiting a newly invented chemi
      ionization source, in combination with headspace vapor measurement at room
      temperature. The calibrated limits of detection (LODs) of 2-methylbutyraldehyde,
      methyl tert-butyl ether (MTBE), methyl methacrylate (MMA), 2-isobutyl-3
      methyoxypyrazine (IBMP), and 2-isopropyl-3-methoxypyrazine (IPMP) are in the
      range of 3.5-50.2 ng L-1, and the estimated LODs of 2-methylisoborneol (2-MIB)
      and geosmin (GSM) are 0.25 and 0.77 ng L-1, respectively. The calibration results
      reveal that the instrumental LODs for 2-methylbutyraldehyde, MTBE, MMA, beta
      cyclocitral, 2-MIB, and GSM are 1-2 orders of magnitude better than the odor
      thresholds of humans. The accuracy, precision, recovery, and linearity (R2) of
      the method are tested. Water samples from city tap water and three rivers in
      Beijing are assessed using this technique, and the typical T&O compositions are
      observed with concentrations ranging from 0.2 to 297 ng L-1. The new ultra
      sensitive rapid detection method shows comparable sensitivities to the existing
      off-line technique and displays great potential for real-time detection of T&O
      pollution in water environments.

PMID- 30224130
TI  - A full-automated magnetic particle-based chemiluminescence immunoassay for rapid
      detection of cortisol in milk.
AB  - A sensitive full-automated micromagnetic particles (MMPs) based competitive
      chemiluminescent immunoassay (CLIA) was developed to detect cortisol in milk.
      Polyclonal antibody (pAb) with good specificity against cortisol was produced.
      The antigen (cortisol-OVA) was labeled with acridinium ester (cortisol-OVA-AE) as
      signal tracer. During the detection, the free cortisol in sample will compete
      with cortisol-OVA-AE for binding to pAb. To capture pAb, MMPs conjugated with
      goat anti-rabbit IgG was added. The whole immunoassay process (exclude sample
      pretreatment) was performed by automatic chemiluminescence immunoassay
      instrument, which could consume less test time (within 40 min) and avoid error
      from manual operation. The method showed a good detection limit of 0.12 ng/mL, a
      broad linear range from 0.42 to 72.27 ng/mL for cortisol detection, negligible
      cross-reactivity with related analogues and satisfied recovery (84.3%-102.3%) for
      spiked milk samples test. Simultaneously, since the results of proposed method
      had no significant difference with those of LC-MS/MS, the proposed method was
      confirmed to have a potential applicability for rapidly monitoring cortisol in
      the food.

PMID- 30224131
TI  - A photoelectrochemical immunosensor based on gold nanoparticles/ZnAgInS
      quaternary quantum dots for the high-performance determination of hepatitis B
      virus surface antigen.
AB  - ZnAgInS quaternary quantum dots were prepared using glutathione as the capped
      reagent. Gold nanoparticles (GNPs) were integrated with ZnAgInS QDs to provide a
      GNPs/ZnAgInS QDs nanocomposite. The morphological image, component and crystal
      structure of GNPs/ZnAgInS QDs were characterized by transmission electron
      microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction
      (XRD). A glassy carbon electrode surface was coated with GNPs/ZnAgInS QDs
      nanocomposites to construct an interface for immobilizing the antibody of
      hepatitis B virus surface antigen (anti-HBsAg). By employing GNPs/ZnAgInS QDs as
      a photoactive element, a photoelectrochemical immunosensor for hepatitis B virus
      surface antigen (HBsAg) was developed. The results indicate that gold
      nanoparticles can dramatically enhance the photocurrent response of ZnAgInS QDs
      and thus improving the sensing performances of the immunosensor. The experimental
      conditions including incubation time, incubation temperature, and ascorbic acid
      concentration were optimized. The relative photocurrent decline [Ri = DeltaI/I0=
      (I0 - I)/I0] shows a linear relationship to the logarithm of HBsAg concentration
      [lg(c, ng mL-1)] in the range from 0.005 to 30 ng mL-1. A detection limit of 0.5
      pg mL-1 was obtained. The immunosensor shows excellent sensitivity, selectivity,
      stability and reproducibility. The HBsAg concentrations in clinical serum samples
      were also accurately determined with this new photoelectrochemical immunosensor.

PMID- 30224132
TI  - Highly-sensitive voltammetric detection of trinitrotoluene on reduced graphene
      oxide/carbon nanotube nanocomposite sensor.
AB  - This work presents the highly-sensitive detection of 2,4,6-trinitrotoluene (TNT)
      on reduced graphene oxide/multi-walled carbon nanotube (rGO/MWCNT) nanocomposite
      sensor. The formation of a thin film of this nanocomposite occurred at the
      cyclohexane/water immiscible interface of a mixture of MWCNT and rGO in the
      biphasic solution. The film was transferred to a boron-doped diamond (BDD)
      electrode for the square-wave voltammetric detection of TNT, which presented
      improved analytical characteristics in comparison with bare BDD and after
      modification with precursors. Electrochemical impedance spectroscopy also
      revealed the faster electron transfer for a redox probe on the nanocomposite
      modified surface. The synergistic properties of both carbon nanomaterials in the
      thin film modified surface resulted in a TNT sensor with a detection limit of
      0.019 MUmol L-1 within a wide linear range (0.5-1100 MUmol L-1), with superior
      performance in comparison with other electrochemical sensors produced with carbon
      nanomaterials. This new material provides great promises for the highly-sensitive
      detection of other nitroaromatic explosives as well as other analytes. Moreover,
      the interfacial method enables the production of homogeneous and stable films on
      large coated areas as well as the large-scale production of electrochemical
      sensors.

PMID- 30224133
TI  - Fabrication of ternary MoS2-polypyrrole-Pd nanotubes as peroxidase mimics with a
      synergistic effect and their sensitive colorimetric detection of l-cysteine.
AB  - Over the past few years, nanomaterials-based enzymatic mimics have attracted
      tremendous attention due to their excellent catalytic activity and environmental
      stability. In this work, ternary MoS2-polypyrrole (PPy)-Pd nanotubes have been
      prepared through a hydrothermal reaction and in situ redox polymerization process
      between pyrrole monomer and Na2PdCl4. The prepared MoS2-PPy-Pd nanotubes
      exhibited a higher peroxidase-like catalytic activity than individual MoS2, MoS2
      PPy, PPy-Pd and MoS2-Pd nanocomposites due to the synergistic catalytic effect
      between the three components. The catalytic kinetic of MoS2-PPy-Pd nanotubes
      follows Michaelis-Menten behaviors, exhibiting a good affinity to both 3,3',5,5'
      tetramethylbenzidine (TMB) and H2O2 substrates. On the basis of high peroxidase
      like catalytic efficiency of the MoS2-PPy-Pd nanotubes, a simple and convenient
      colorimetric strategy for the rapid and sensitive detection of l-cysteine with a
      detection limit of 0.08 MUM has been developed. In addition, a high selectivity
      towards the detection of l-cysteine is achieved. This work present an opportunity
      of the prepared ternary MoS2-PPy-Pd nanotubes for promising potential
      applications in biosensing, environmental monitoring, and medical diagnostics.

PMID- 30224134
TI  - Silicon nanodot-based aptasensor for fluorescence turn-on detection of mucin 1
      and targeted cancer cell imaging.
AB  - We report herein a new dual-color fluorescent aptasensor for detection of tumor
      marker mucin 1 (MUC1) and targeted imaging of MCF-7 cancer cells based on the
      specific interaction between MUC1 and its aptamer S2.2. The aptasensor was
      prepared by covalent attachment of the cyanine (Cy5)-tagged aptamer S2.2 to
      fluorescent silicon nanodot (SiND). The fluorescence of S2.2-Cy5 could be
      quenched by the SiND carrier in the absence of MUC1, and its fluorescence was
      restored in the presence of MUC1 due to structure switching of S2.2. This
      aptasensor exhibits specificity for MUC1-possitive MCF-7 cells rather than MUC1
      negative MCF-10A cells and Vero cells. The SiND plays multiple roles in this
      fluorescence assay, making the method easier compared with other approaches. The
      limit of detection and precision of this method for MUC1 was 1.52 nM and 3.6% (10
      nM, n = 7), respectively. The linear range was 3.33-250 nM, and the recoveries in
      spiked human serum were in the range of 87-108%. This is a simple, selective,
      sensitive and reliable method, which can well achieve not only quantitative
      analysis of tumor marker but also dual-color visualization of single cancer
      cells.

PMID- 30224135
TI  - A novel one- and two-photon fluorescent probe induced by light for selective
      imaging of Cys in living cells and tissues.
AB  - A novel one- and two-photon fluorescent probe based on a photoreaction was
      developed for the detection of cysteine (Cys). After it was reacted with Cys and
      illuminated by light, a strong turn-on fluorescence was observed at the
      excitation of 390 nm. The probe IC-2 was well tolerated at physiological pH
      conditions and exhibited a fast response rate to Cys within 10 min. Moreover, the
      probe IC-2 displayed high selectivity towards Cys among other amino acids and
      metal ions. Fluorescence response studies suggested that the limit of detection
      of IC-2 was calculated as 2.6 * 10-8 M. An MTT assay demonstrated that IC-2 had
      good cell permeability and low cytotoxicity to HepG2 cells. Notably, IC-2 was
      successfully applied in one- and two-photon fluorescence imaging for Cys in
      living cells and tissues.

PMID- 30224136
TI  - A novel and sensitive chemiluminescence immunoassay based on AuNCs@pepsin@luminol
      for simultaneous detection of tetrabromobisphenol A bis(2-hydroxyethyl) ether and
      tetrabromobisphenol A mono(hydroxyethyl) ether.
AB  - A novel chemiluminescence immunoassay based on luminol-modified gold nanoclusters
      (AuNCs@Peps@luminol) was developed for simultaneous detection of
      tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA-DHEE) and
      tetrabromobisphenol A mono(hydroxyethyl) ether (TBBPA-MHEE), an important
      derivative and byproduct of tetrabromobisphenol A (TBBPA), respectively. In the
      system, alkaline phosphatase (ALP) was labeled on the second antibody (Ab2) for
      signal amplification. When ALP-Ab2 was captured by antigen-primary antibody (Ab1)
      complex, disodium phenyl phosphate (PPNa) generated massive phenol under the
      catalysis of ALP, markedly inhibiting the chemiluminescence intensity of
      AuNCs@Peps@luminol. Under the optimized conditions, the calculated detection of
      limit (LOD, 90% inhibition) was 0.078 MUg/L for TBBPA-DHEE with a linear range of
      0.23-9.32 MUg/L, which was lower 9 times than that of conventional ELISA with the
      same antibody. In addition, our method showed satisfactory accuracy and precision
      (recoveries, 88.00-113.4%; CV, 2.75-8.14%), it can be applied to systematically
      investigate the concentration of the trace TBBPA-DHEE and TBBPA-MHEE in
      environmental and food samples.

PMID- 30224137
TI  - A highly sensitive peptide-based biosensor using NiCo2O4 nanosheets and g-C3N4
      nanocomposite to construct amplified strategy for trypsin detection.
AB  - Here, a simple electrochemical biosensor was proposed based on the specific
      recognition between trypsin and peptide. Initially, NiCo2O4-PAMAM nanocomposite
      was casted on the bare electrode to achieve the electrochemical signal
      amplification in 0.1 mM [Ru(NH3)6]3+ solution owing to the great electronic
      conductivity and high electrochemical activity induced by the special structure
      of NiCo2O4 nanosheets (Ni3+ cations in octachedral sites of the Co3O4).
      Subsequently, a declined electrochemical signal was obtained when g-C3N4 labeled
      peptide composites were anchored on the electrode. However, after trypsin was
      added into solution and incubated with the biosensor, the electrochemical signal
      was re-promoted. Therefore, the as-synthesized biosensor could realize the
      sensitive detection of trypsin by virtue of the specific recognition between
      trypsin and peptide. As a result, the developed peptide-based exhibited a linear
      range from 10-10 to 10-4 mg mL-1 with an ultralow detection limit of 10-10 mg mL
      1, providing sensitive analytical performance and acceptable application
      potential in clinical test and disease diagnosis due to its high stability,
      excellent selectivity, acceptable reproducibility and accurate signal output.

PMID- 30224138
TI  - Copper nanoclusters/polydopamine nanospheres based fluorescence aptasensor for
      protein kinase activity determination.
AB  - A fluorescence aptasensor was constructed for protein kinase (PKA) activity
      detection by utilizing copper nanoclusters (CuNCs) and polydopamine nanospheres
      (PDANS). Through the pi-pi stacking interactions between adenosine triphosphate
      (ATP) aptamer and PDANS, the ATP aptamer modified CuNCs (apt-CuNCs) were absorbed
      onto PDANS surface, thus the fluorescence of apt-CuNCs were quenched through
      fluorescence resonance energy transfer (FRET) from apt-CuNCs to PDANS. In the
      presence of ATP, ATP specifically bound to aptamer, causing the dissociation of
      apt-CuNCs from PDANS surface and restoring the fluorescence of apt-CuNCs.
      However, PKA translated ATP into adenosine diphosphate (ADP), and ADP had no
      competence to combine with ATP aptamer, thus, apt-CuNCs were released and
      absorbed onto the PDANS surface to cause the fluorescence quenching of apt-CuNCs
      again. Therefore, PKA activity was conveniently detected via the fluorescence
      signal change. Under the optimal conditions, PKA activity was detected in the
      range of 0.05-4.5 U mL-1 with a detection limit of 0.021 U mL-1. Furthermore, the
      feasibility of the aptasensor for kinase inhibitor screening was explored via
      assessment of kinase inhibitor H-89 as one model. This aptasensor was also
      performed for PKA activity determination in HepG2 cell lysates with satisfactory
      results.

PMID- 30224139
TI  - Red emission nitrogen, boron, sulfur co-doped carbon dots for "on-off-on"
      fluorescent mode detection of Ag+ ions and l-cysteine in complex biological
      fluids and living cells.
AB  - Herein, a simple and efficient fluorescent assay for Ag+ ions and l-cysteine (L
      Cys) in complex biological fluids and living cells was first developed based on
      the fluorescent "on-off-on" mode of red emission nitrogen, boron, sulfur co-doped
      carbon dots (NBS-CDs). Red emission NBS-CDs were prepared via one-step
      hydrothermal synthesis by using 3-aminobenzeneboronic acid and 2,5
      diaminobenzenesulfonic acid as precursors. Such NBS-CDs exhibited excellent
      optical properties and relatively high absolute fluorescent quantum yield
      compared with some reported NBS-CDs. Due to the strong quenching ability of Ag+
      ions on the fluorescence of NBS-CDs, red emission NBS-CDs were used for the
      determination of Ag+ ions with high sensitivity and excellent selectivity. The
      fluorescence of NBS-CDs was recovered after the interaction between Ag+ ions and
      L-Cys, which realized the specific determination of L-Cys in human urine samples
      and human plasma samples. The established NBS-CDs-based fluorescent "on-off-on"
      sensor offered a relatively low detection limits of 0.35 MUM for Ag+ ions and
      0.045 MUM for L-Cys based on three times signal-to-noise criteria. Notably, this
      strategy was applied for the visual detections of Ag+ ions and L-Cys in living
      human cancer cells (HeLa cells and MCF-7 cells). This method is simple, high
      sensitive, and excellent selectivity, which provided a new insight on the
      potential applications of NBS-CDs to develop the biosensor in clinical diagnosis
      and other biologically related areas.

PMID- 30224140
TI  - Functional preserving carbon dots-based fluorescent probe for mercury (II) ions
      sensing in herbal medicines via coordination and electron transfer.
AB  - Mercury ions (Hg2+) are one of the compulsory items in the quality control of
      herbal medicines for its serious toxicity to human health. Highly selective and
      sensitive Hg2+ detection, especially in complex real samples, is still
      challenging. In this work, Fluorescent (FL) carbon dots (CDs) with a core-shell
      structures composed of the crystalline core of stacked sp2-hybridized carbon
      layers and the shell of functional groups on the periphery of carbon layers are
      facilely prepared through a one-step hydrothermal synthetic route. They can
      specifically interact with Hg2+ in aqueous medium to form aggregates, during
      which coordination of carboxyl functional groups on the surface of CDs with Hg2+
      occurred, which facilitated electron transfer from the CDs to Hg2+. As a result,
      fluorescence of the CDs was quenched with a high efficiency, making the detection
      of Hg2+ highly sensitive with the limit of determination (LOD) of 2.2 nM
      (3sigma). With that, detection of Hg2+ in the complex compound herbal medicines
      samples with highly reproducible results has been successfully realized by using
      the as-prepared CDs, showing that fluorescent CDs-based probe may have great
      potential in the quality controls of heavy metals for pharmaceutical analysis.

PMID- 30224141
TI  - Synthesis and characterization of the thermally reduced graphene oxide in argon
      atmosphere, and its application to construct graphene paste electrode as a
      naptalam electrochemical sensor.
AB  - New insight into the preparation of sensitive carbon-based electrochemical
      electrode is provided by examining the properties of thermally reduced graphene
      oxide (TRGO). In this paper, TRGO was prepared by thermal reduction of graphene
      oxide (GO) in argon atmosphere, and characterized by Fourier transform infrared
      (FTIR) spectroscopy, transmission electron microscopy (TEM), selected area
      electron diffraction (SAED), and atomic force microscopy (AFM). Results showed
      that thermal reduction in argon was effective to remove oxygen-containing
      functional groups in GO, and graphene sheets were obtained. Furthermore, TRGO was
      used to prepare thermally reduced graphene oxide paste electrode (TRGOPE) which
      showed excellent conductivity and fast electron transfer kinetics confirmed by
      electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The
      electrode was applied to determination of the pesticide naptalam (Nap) in square
      wave voltammetric (SWV) mode. The corresponding current at approx. +1.0 V
      increased linearly with the Nap concentration within two linear dynamic ranges
      (LDR) of 0.1-1.0 MUmol L-1 (LDR1) and 1.0-10.0 MUmol L-1 (LDR2). The limits of
      detection (LOD) and quantification (LOQ) for Nap were calculated as 0.015 MUmol L
      1 and 0.051 MUmol L-1, respectively. In comparison to the carbon paste electrode
      (CPE) the results showed that the TRGOPE possesses advantages in terms of
      linearity, sensitivity and detectability.

PMID- 30224142
TI  - Comparison of different speciation techniques to measure Zn availability in
      hydroponic media.
AB  - Four analytical techniques are compared: AGNES (Absence of Gradients and
      Nernstian Equilibrium Stripping), LASV (Anodic Stripping Voltammetry with Linear
      stripping), DGT (Diffusive Gradients in Thin films) and PIM (Polymer Inclusion
      Membranes). These techniques have been designed to provide the free ion
      concentration or a labile fraction, complementarily contributing to an integrated
      description of speciation and availability. Their simultaneous application to the
      determination of free Zn concentrations or labile fluxes in seven solutions of a
      hydroponic medium reveals characteristics of each technique and correlations
      between their results. All dynamic results can be interpreted in terms of a
      general theoretical framework on fluxes. Indeed, in techniques under diffusion
      limited conditions in the sample, the flux can be split into the free
      contribution (linearly proportional to the free fraction), plus the contribution
      of the complexes (where mobility, lability and abundance of complexation are
      intertwined). A methodology to compute lability degrees is developed.
      Measurements with PIM devices confirm that diffusion in the sample solution is
      not rate limiting, so its flux is proportional to the free metal in the donor
      solution. A proportionality between the responses of any given two techniques is
      observed, which suggests that, for the low ligand-to-metal concentration ratios
      used in the present work, any of these techniques would correlate similarly with
      uptake, toxic or nutritional measurements.

PMID- 30224143
TI  - Nanoporous platinum electrode grown on anodic aluminum oxide membrane:
      Fabrication, characterization, electrocatalytic activity toward reactive oxygen
      and nitrogen species.
AB  - A new type of nanoelectrode, nanoporous platinum (NPt) electrode was prepared on
      aluminum oxide membrane by thermal evaporation deposition. The morphology,
      conductivity and electrocatalytic activity of NPt electrode were characterized
      and compared with those of nanofilm-Pt electrode through scanning electron
      microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic
      voltammetry (CV) techniques, respectively. SEM images showed that "nanocavities"
      observed in NPt electrode were actually 2-dimensional enclosures by linked
      nanoparticles. It was different from the conventional arrays of "nanocavities"
      formed on homogeneous metal films. EIS data indicated that NPt electrode
      possesses higher conductivity. Compared with that on nanofilm-Pt electrode (14.05
      Omega.cm2), the impedance spectrum on NPt electrode exhibits a semicircle portion
      with much smaller diameters (1.24 Omega.cm2 for NPt-100, 1.48 Omega.cm2 for NPt
      200). Meanwhile, the response sensitivity of NPt electrode to O2 is 0.85 mA cm-2,
      which is larger than that of nanofilm-Pt electrode (0.54 mA cm-2). The largest
      catalytic current for nitric oxide (NO) was obtained in buffer with pH value of
      9.4 while for Angeli's salt (AS) was obtained in buffer with pH value of 5.4.
      Additionally, electrocatalytic mechanisms of NPt electrode toward NO and AS were
      proposed, which indicating it depended on pH value of buffer solution.

PMID- 30224144
TI  - Enhanced catalytic capability of electroactive biofilm modified with different
      kinds of carbon nanotubes.
AB  - In this study two methods including coating carbon nanotubes (CNTs) layers on the
      electrode surface and adding CNTs-suspension during electrochemically active
      biofilms (EABs) growth were used, respectively, to develop CNTs hybrid EABs for
      enhancing electricity generation capability of EABs. EABs growth on the CNTs with
      functional groups of hydroxyl (CNTs-OH) or carboxyl (CNTs-COOH) and pristine CNTs
      without functionalization (P-CNTs) modified electrode was investigated. The
      maximum current densities of EABs growth on the P-CNTs, CNTs-OH and CNTs-COOH
      coated electrode were respective 1300 +/- 117, 1082 +/- 54 and 1124 +/- 78 MUA cm
      2, which were much higher than unmodified electrode (663 MUA cm-2). Meanwhile,
      EABs growth in doping CNTs-COOH or CNTs-OH suspensions system also produced twice
      higher current density than that on unmodified electrode. These results indicated
      that the current production of EABs can be significantly enhanced by coating P
      CNTs, CNTs-OH, CNTs-COOH layers on the electrode surface or doping CNTs-OH and
      CNTs-COOH suspension into EABs. Furthermore, morphology analysis of as-obtained
      EABs had also been studied. It was found that there was no significant difference
      of the morphological characteristic for EABs growth on different types CNTs
      coated electrode surface. By comparison, a nano-hybrid porous structure of CNTs
      and EABs was observed when CNTs-COOH or CNTs-OH suspension was added into the
      medium during EABs growth, which will be responsible for high current generation.

PMID- 30224145
TI  - A photoswitchable "host-guest" approach for the selective enrichment of
      dimethoate from olive oil.
AB  - This work describes the development of a new selective photocontrollable
      molecularly imprinted-based sorbent for the selective enrichment/pre
      concentration of dimethoate from spiked olive oil samples. To achieve this goal
      an improved molecularly imprinted strategy relying on the embedding of a
      functional monomer containing an azobenzene chromophore as light-responsive
      element, on the crosslinked tridimensional molecular imprinted network, has been
      assessed. To address the mechanisms underlying template recognition and
      uptake/release of the analyte from the functional imprinted material,
      computational studies using a quantum chemical approach, have been explored. This
      new functional sorbent provides a straightforward controllable uptake/release of
      the target template using light as the stimuli tool, which is highly advantageous
      due to light manipulation characteristics, such as superior clean, precision and
      remote controllable properties. In general, this work will contribute to the
      implementation of a photoswitchable analytical methodology that proves to be
      suitable for the selective isolation and further quantification of dimethoate
      from olive oil matrices at levels similar to the maximum residues limits imposed
      by the legislation. The limits of detection, calculated based on 3sigma, was 1.6
      mgL-1 and the limit of quantification, based on 10sigma, was 5.2 mgL-1. The
      implemented sample preparation shows high reproducibility and recoveries (93.3 +/
      0.4%).

PMID- 30224146
TI  - Dual-functional polymer-modified magnetic nanoparticles for isolation of
      lysozyme.
AB  - An artificial receptor approach for proteins capture and release was designed
      based on ionic-sensitive and thermo-sensitive functionalized polymers, which were
      modified onto the surface of magnetic nanoparticles. The dual-functional
      poly(styrene-sulfonate-N-isopropylacrylamide) (P(SS-NIPAm)) was synthesized via
      the free radical polymerization method and used as the artificial receptor with
      electrostatic, hydrophilic and hydrophobic properties. The affinity between the
      artificial receptor and lysozyme was investigated using high performance liquid
      chromatography. Arising from the strong and specific interactions between the
      negatively charged sulfonic acid groups of P(SS-NIPAm) and positively charged
      amino groups of the protein, the prepared artificial receptor exhibited
      outstanding affinity for lysozyme. Interestingly, due to the thermo-responsive
      and ionic strength-responsive features of the prepared P(SS-NIPAm), the capture
      and release process for lysozyme could be modulated by varying the environmental
      temperature and ionic strength. Further, the proposed artificial receptor based
      on P(SS-NIPAm) modification of magnetic nanoparticles surface was used for
      affinity capture of lysozyme in human serum with a recovery ranging from 89.9% to
      100.4%, paving a new way for synthesis of artificial receptors and showing great
      potential for recognition of target protein in real bio-samples.

PMID- 30224147
TI  - Automation of ionic liquid enhanced membrane bag-assisted-liquid-phase
      microextraction with liquid chromatography-tandem mass spectrometry for
      determination of glucocorticoids in water.
AB  - A novel fully automated liquid-phase microextraction (LPME) procedure making use
      of a conical polypropylene membrane bag to hold the solvent, coupled with ultra
      high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)
      with positive electrospray ionisation was developed to determine glucocorticoids
      (including cortisol, cortisone, dexamethasone, prednisone and prednisolone) in
      water. The solvent was a synergistic mixture of 10% v/v of ionic liquid, 1-butyl
      3-methylimidazolium methylsulfate in n-octanol. The use of ionic liquid as an
      additive enhanced the extraction performance due to the favourable ionic and
      hydrogen bonding interactions with the analytes. Different experimental
      parameters such as the types of organic solvent as supported liquid membrane and
      ionic liquid, various composition of ionic liquid, volume of extractant phase,
      agitation time and speed, temperature of extraction were investigated. Under the
      most favourable extraction conditions, enrichment factors of 49.4-83.1 were
      obtained for the target compounds with relative standard deviations of <10%. The
      intra-day repeatability of the method ranged from 4.23 to 6.42% and the inter-day
      reproducibility ranged from 6.87 to 9.20%. Good linearity 0.05-50 ng mL-1
      (prednisolone) and 0.1-50 ng mL-1 (all other analytes) with coefficients of
      determination of 0.991 or better, was obtained. The membrane bag-assisted-LPME
      UHPLC-MS/MS approach exhibited high sensitivity, linearity and repeatability for
      the extraction of the glucocorticoids and also offered an automated streamlined
      process, from the point where analytes were extracted, to the final analysis of
      the water samples. The method was employed to determine the concentration of
      these contaminants in the influent and effluent of a wastewater treatment plant.

PMID- 30224148
TI  - A rapid LC-MS method for qualitative and quantitative profiling of plant
      apocarotenoids.
AB  - Carotenoid cleavage products (apocarotenoids; APOs) exert important biological
      functions in light perception and as vitamin A source, signaling molecules,
      hormone precursors, pigments and volatiles. However, an analytical method that
      allows simultaneous profiling of these diverse compounds is still missing. We
      developed an efficient method to analyze APOs present in plant tissues, which is
      based on ultra-high performance liquid chromatographic separation and high
      resolution hybrid quadrupole-Orbitrap (Q-Orbitrap) mass spectrometry (MS). Our
      approach allowed unambiguous identification and quantification of volatile and
      non-volatile APOs in a single run. Modified sample preparation and optimized
      ultra-high performance liquid chromatography (UHPLC)-MS parameters permitted the
      measurement of APOs in Oryza sativa seedlings and Spinacia oleracea leaves,
      unraveling 20 endogenous APOs with chain lengths ranging from C10 to C30,
      confirmed by high-resolution MS, MS/MS data and using synthetic standards. Our
      experimentation demonstrates that the usage of methanol with 0.1% butylated
      hydroxytoluene facilitates the extraction of both short-chain and long-chain APOs
      from plant materials. In addition, our validated analytical method allows the
      quantitative analysis of APOs with a wide content range from 2.5 pg/mg to 10
      ng/mg dried weight. The adoption of the analytical protocol, as described in this
      study, realizes the measurement of volatile APOs by using a LC-MS method, hence,
      allowing informative and reliable profiling of APOs, which is important for
      determining the content of these compounds in food and crucial for understanding
      their function and metabolism in plants.

PMID- 30224150
TI  - Effectiveness and cost-effectiveness of early nutritional support via the
      parenteral versus the enteral route for critically ill adult patients.

PMID- 30224149
TI  - Evaluation of two-step liquid-liquid extraction protocol for untargeted metabolic
      profiling of serum samples to achieve broader metabolome coverage by UPLC-Q-TOF
      MS.
AB  - Untargeted metabolomics studies aim to extract a broad coverage of metabolites
      from biological samples, which largely depends on the sample preparation
      protocols used for metabolite extraction. The aim of this study was to evaluate a
      comprehensive sample pretreatment strategy using two-step liquid-liquid
      extraction to achieve broader metabolome coverage by ultra-high-performance
      liquid chromatography coupled with electrospray ionization time-of-flight mass
      spectrometry (UPLC-Q-TOF-MS). We compared four protocols: (A) methanol protein
      precipitation, (B) Ostro 96-well plates, (C) two-step extraction protocol of
      CHCL3-MeOH followed by MeOH-H2O, and (D) two-step extraction protocol of CH2CL2
      MeOH followed by MeOH-H2O. The number of extracted features, reproducibility and
      recovery were the major criteria for evaluation. Our results demonstrated that
      Protocols B, C and D, with approximately similar number of features, extracted
      more features than Protocol A. Protocols C and D appeared to have similar
      extraction reproducibility (low coefficient of variation < 30%) and Protocol D
      enabled an acceptable recovery of serum metabolites. The two-step extraction
      Protocol D (CH2CL2-MeOH followed by MeOH-H2O) resulted in the greatest
      improvement in metabolite coverage, satisfactory extraction reproducibility,
      acceptable recovery and environmental safety. The selected protocol was applied
      to an obesity metabolomics study to obtain different metabolites between
      participants with obesity and the controls, and to investigate complex metabolic
      alterations in obesity during a 2-h oral glucose-tolerance test. Our results
      suggested that this protocol was useful for analyzing serum metabolome changes in
      obese individuals in the fasting and postprandial state.

PMID- 30224151
TI  - Mid-bundle positioning of the femoral socket increases graft rupture in anatomic
      single bundle anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Anatomic anterior cruciate ligament (ACL) reconstructions are
      superior to non-anatomic graft placements with regard to controlling rotational
      laxity. Different techniques of anatomic single-bundle reconstruction exist. The
      femoral tunnel may be placed in a mid-bundle position (MB) or within the
      anteromedial bundle footprint (AM) with no definitive consensus as to the
      preferred position. Our institution, reflecting trends in surgical practice, has
      experience with both techniques. METHODS: Interrogation of our prospectively
      maintained database yielded all primary ACL reconstructions performed using the
      anatomic TransLateral single-bundle all-inside technique. A two year minimum
      follow-up was set. The failure rate of the MB and AM cohorts was compared as a
      primary outcome. Patient-reported outcomes across cohorts at several time-points
      were analysed as a secondary outcome. RESULTS: Two hundred and seventy-nine
      primary ACL reconstructions were identified at a median follow-up of 49 months.
      MB positioning was utilised in 113 cases (40.5%) and AM positioning in 166
      (59.5%). There were significantly more failures in the MB cohort (p = 0.029).
      Logistic regression revealed mid-bundle femoral positioning was associated with
      greater than fourfold increase in graft failure (odds ratio 4.14, p = 0.039).
      CONCLUSION: Data from this case series suggests that amongst anatomic single
      bundle ACL reconstructions, grafts with a mid-bundle femoral tunnel are more than
      four times more likely to fail versus those with a femoral tunnel placed four
      millimetres deeper within the anteromedial bundle footprint.

PMID- 30224153
TI  - Trends in peripheral stem/progenitor cell manipulation and clinical application.
AB  - Transplants using peripheral blood hemopoietic stem/progenitor (PBHS) cells are
      widely performed for the treatment of patients with hematologic disorders in
      routine practice and clinical trials. Although the process from mobilization to
      infusion of PBHS cells has been mostly established, optimal conditions for each
      process remain undetermined. Adverse reactions caused by PBHS cell infusions have
      not been systematically recorded. In transplants using PBHS cells, a number of
      problems still exist. In this section, the current status of and future
      perspectives regarding PBHS cells are described.

PMID- 30224152
TI  - Released washed platelet concentrates are effective and safe in patients with a
      history of transfusion reactions.
AB  - BACKGROUND: Plasma removal by washing is an effective approach to prevent
      transfusion reactions by platelet concentrates (PCs). Recently, washed PCs were
      released by the Japanese Red Cross Society (JRCS). MATERIALS AND METHODS: This
      retrospective multicenter study evaluated the efficacy and safety of released
      washed PCs (RWPCs) between September 2016 and January 2017 in Japan. The RWPCs
      were prepared by washing leukoreduced apheresis PCs with the platelet additive
      solution, BRS-A, using automated cell processors. RESULTS: Clinical data were
      obtained from 91 patients and 1210 RWPC transfusions at 50 institutions. The
      median number of RWPC transfusions per patient was 8 (range, 1-91). RWPCs were
      used in 94.5% of the patients with a history of recurrent or severe transfusion
      reactions for preventing such reactions. Responses of RWPCs were evaluated as
      complete response (91.6%), partial response (8.2%), no-change (0.2%), and
      progression (0%) and overall response was equal across subgroups divided by
      patients' profiles. The median corrected count increment (CCI) at 1 and 24 h post
      transfusion were 13.5 (range, 1.9-35.4) * 109/L and 3.5 (range, -13 to 53.6) *
      109/L, respectively, and median CCI at 24 h was 5.5 (range, -13 to 53.6) * 109/L
      in patients without risk factors associated with platelet transfusion
      refractoriness. Transfusion reactions to RWPCs were observed in only nine
      transfusions (0.7%), all of which were mild allergic reactions. CONCLUSION: This
      study demonstrated that RWPCs were effective and safe in patients with a history
      of transfusion reactions. Further prospective studies on efficacy together with
      cost-benefit analysis in RWPCs are needed.

PMID- 30224154
TI  - "Technophilia": A new risk factor for electronic cigarette use among early
      adolescents?
AB  - PURPOSE: Develop and validate a scale that measures Technophilia (positive
      orientation toward new technology) and use it to address orientation toward new
      technologies to explain e-cigarette trial and adoption, especially in relatively
      low risk adolescents. METHODS: Survey data were obtained from students of the
      three largest cities in Mexico (n = 8123). We developed eight questions involving
      access, use and pleasure from different electronic media to measure technophilia.
      Exploratory factor analysis (EFA) was conducted. Linear GEE models were used when
      regressing technophilia on covariates. When regressing e-cigarette and
      conventional cigarette trial and use, logistic GEE models were used. Finally, we
      used multinomial logistic regression to evaluate the associations between
      technophilia and e-cigarettes as the first tobacco product. RESULTS: Technophilia
      were correlated with theoretically-related variables. Unadjusted and adjusted
      models regressing e-cigarette trial and use indicated that students in the
      highest quartile for technophilia were more likely to have tried e-cigarettes
      compared with the lowest quartile (AORQ4 vs Q1 = 1.36, 95% CI 1.14-1.62).
      Technophilia was not independently associated with current e-cigarette use in
      adjusted models. Students with higher technophilia were more likely to have first
      tried e-cigarettes in both crude and adjusted models (AORQ4vQ1 = 1.66, 95% CI
      1.20-2.31; AORQ3vQ1 = 1.43, 95% CI 1.02-2.01). Technophilia did not have a
      statistically significant, independent association with first use of other
      tobacco products. CONCLUSION: This study suggests that technophilia is associated
      with trial of e-cigarettes among youth. The measure we developed appears useful
      for understanding why some youth are open to trying novel, technologically
      oriented ways to consume nicotine.

PMID- 30224155
TI  - Electronic nicotine delivery systems (e-cigarettes) as a smoking cessation aid: A
      survey among pharmacy staff in Queensland, Australia.
AB  - OBJECTIVES: This study examined views of pharmacy staff regarding the safety of e
      cigarettes compared to nicotine replacement therapies (NRTs) and conventional
      cigarettes, as well as views on their regulation in Australia. METHODS: We
      conducted a cross-sectional survey among pharmacy staff (64 pharmacists and 76
      pharmacy assistants) from the greater Brisbane region, Queensland, Australia. The
      self-administered questionnaire included closed- and open-ended questions that
      explores pharmacy staff perception on harms of e-cigarettes versus NRT and
      traditional cigarettes, knowledge of current e-cigarette regulations, views on
      how they should be regulated and information needs regarding e-cigarettes.
      Pearson's chi-square test was employed for computing differences between
      variables. A content analysis of responses to open-ended questions was also
      performed. RESULTS: Over 90% of pharmacy staff regarded e-cigarettes without
      nicotine and NRTs as less harmful than regular tobacco cigarettes. This reduced
      to 72% for e-cigarettes containing nicotine, with 24% of respondents believing
      they are equally as harmful as conventional cigarettes. Moreover, few respondents
      were confident about the short and long term safety of e-cigarettes containing
      nicotine (36% and 15% respectively) whereas pharmacy staff were more comfortable
      with the safety of NRTs for short (88%) and long term (35%) use. The majority of
      respondents believed that e-cigarettes with nicotine should be regulated as a
      medicine, either requiring a prescription (24%) or sold only by pharmacies (22%),
      though many believed that they should be regulated in the same way as regular
      tobacco cigarettes (27%). Some pharmacy staff (39%) reported having been asked
      about e-cigarettes by customers and 75% believed that their customers would be
      interested in using e-cigarettes as a smoking cessation aid. CONCLUSIONS: There
      is a need to provide evidence-based and customised education for pharmacists
      regarding e-cigarettes to help them guide their clients.

PMID- 30224156
TI  - Targeted Base Editing Systems Are Available for Plants.
AB  - Use of RNA-guided endonucleases for targeted genome editing is one of the most
      important breakthrough discoveries of the 21st century. Recent studies have
      described modifications of this precise base editing technique that open up a new
      dimension to plant genome editing.

PMID- 30224157
TI  - G-Quadruplexes: More Than Just a Kink in Microbial Genomes.
AB  - G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by
      guanine-rich DNA and RNA sequences. In this review we aim to provide an overview
      of the biological roles of G4s in microbial genomes with emphasis on recent
      discoveries. G4s are enriched and conserved in the regulatory regions of
      microbes, including bacteria, fungi, and viruses. Importantly, G4s in hepatitis B
      virus (HBV) and hepatitis C virus (HCV) genomes modulate genes crucial for virus
      replication. Recent studies on Epstein-Barr virus (EBV) shed light on the role of
      G4s within the microbial transcripts as cis-acting regulatory signals that
      modulate translation and facilitate immune evasion. Furthermore, G4s in microbial
      genomes have been linked to radioresistance, antigenic variation, recombination,
      and latency. G4s in microbial genomes represent novel therapeutic targets for
      antimicrobial therapy.

PMID- 30224158
TI  - Surgical treatments for tremors.
AB  - Stereotactic surgery is an increasingly popular option for disabling tremors
      whenever it is insufficiently improved by drug treatment. Surgical approaches are
      expanding. Thalamic deep brain stimulation is one of the most efficacious
      treatments. Its recent technological advances with adaptive stimulation and new
      electrodes configuration will allow a more physiological stimulation. However, a
      reappraisal of less invasive, new lesioning procedures is underway. Gamma Knife
      thalamotomy and magnetic resonance-guided focused ultrasounds encounter very few
      contraindications. Recent studies reported their efficacy on tremor control and
      safety profile. Besides the ventralis intermedius nucleus of the thalamus,
      alternative targets are also emerging. The effectiveness of surgical therapies on
      essential tremor and Parkinson's disease tremor is well established. For more
      uncommon tremors, preliminary studies are encouraging. All these surgical
      therapies can be proposed as treatment option for medically refractory tremors.

PMID- 30224159
TI  - Hyperdopaminergic behavioral spectrum in Parkinson's disease: A review.
AB  - Impulse control disorders (ICDs) and other related behaviors, such as punding and
      dopamine dysregulation syndrome, are frequent yet underrecognized non-motor
      complications of dopamine replacement therapy (DRT) in Parkinson's disease (PD);
      they can also have a major negative impact on quality of life. They result from
      complex interactions between a given individual's predispositions, non
      physiological dopaminergic stimulation and PD pathology. Also, sensitization of
      the mesocorticolimbic pathway, reflected by the psychotropic effects of
      dopaminergic treatment, plays a crucial role in the emergence of these addictive
      behaviors. While early detection of changes in behavior, less use of dopamine
      agonists (DA) that have a relative selectivity for mesocorticolimbic dopamine
      receptors, and fractionation of levodopa dosages to avoid non-physiological
      pulsatile stimulation of dopamine receptors are key strategies in the management
      of this hyperdopaminergic behavioral spectrum, other complementary approaches are
      also addressed in this review.

PMID- 30224160
TI  - How to get by with half a loop - An investigation of visual and auditory codes in
      a case of impaired phonological short-term memory (pSTM).
AB  - In the field of cognitive neuropsychology of phonological short-term memory
      (pSTM), a key debate surrounds the issue of how impairment on tasks deemed to tap
      this system imply a dissociable phonological input and output buffer system, with
      the implication that impairments can be fractionated across disruption to
      separate functional components (Nickels, Howard & Best, 1997). This study
      presents CT, a conduction aphasic who showed no impairment on basic auditory
      discrimination tasks, but had very poor nonword repetition. Clear-cut examples of
      such cases are very rare (see Jacquemot, Dupoux & Bachoud-Levi, 2007), and we
      interpret the case with reference to a pSTM model that includes input and output
      buffers. The dissociation between performance on auditory phonological tasks and
      visual phonological tasks we interpret as consistent with disruption to the link
      from input buffer to output buffer without concurrent damage to connections from
      output to input. Previous research has also shown that patients with impairments
      of pSTM can make visual confusions with orthographically presented items in tasks
      seeking to tap this mechanism (Warrington & Shallice, 1972), which might stem
      from having an incomplete pSTM loop. In light of this we examined whether CT's
      ability on tests of ISR was affected by visual orthographic similarity among list
      items, and this is indeed what we observed. On balance then, CT's overall profile
      is considered best interpreted with respect to a dual buffer pSTM model (e.g.,
      Vallar & Papagno, 2002).

PMID- 30224161
TI  - International Congress on Soldiers' Physical Performance 2017 (ICSPP2017) Special
      Issue.

PMID- 30224162
TI  - Transient posterior cerebral arteriopathy: An unusual case enterovirus-related.
AB  - Transient Cerebral Arteriopathy (TCA) is one of the main causes of childhood
      stroke. Here we present an unusual case of Arterial Ischemic Stroke (AIS) caused
      by a TCA of posterior flow and originally located in the right thalamus. The
      detection of enterovirus in the cerebrospinal fluid allowed us to suppose a
      probable post infectious etiology. The course of symptoms was self-limited and
      the child had a complete clinical recovery after five days. A new ischemic lesion
      on the antero-inferior paravermian region of the left cerebellum was revealed by
      a following brain Magnetic Resonance Imaging (MRI) three months later and these
      findings were reported by further brain MRI control performed after 15 months.
      Comparing follow up Magnetic Resonance Angiography (MRA) with previous High
      Resolution Vessel Wall Magnetic Resonance Imaging (HRMI), we found a vessel
      narrowing at the level of the Posterior Inferior Cerebellar Artery that might
      explain the arteriopathy process. In conclusion, clinical and radiological course
      allow us to speculate that this multifocal cerebral arteriopathy might be a
      transient lesion due to enterovirus infection. To our knowledge, there are only
      three articles describing TCA enterovirus-related, and brain MRA was performed in
      only one case; in addition, no one with the involvement of the posterior
      circulation.

PMID- 30224163
TI  - Editorial overview: Chemical biotechnology.

PMID- 30224165
TI  - The amounts of melanin pigment causing color differences between the vermilion
      and lip mucosa.

PMID- 30224166
TI  - Optimising exposure of the coronoid process during lengthening temporalis
      myoplasty for facial reanimation.

PMID- 30224164
TI  - Non-uniformity in the healthy patellar tendon is greater in males and similar in
      different age groups.
AB  - There is increasing evidence that tendons are heterogeneous and take advantage of
      structural mechanisms to enhance performance and reduce injury. Fascicle-sliding,
      for example, is used by energy-storing tendons to enable them to undergo large
      extensions while protecting the fascicles from damage. Reductions in fascicle
      sliding capacity may thus predispose certain populations to tendinopathy.
      Evidence from the Achilles tendon of significant superficial-to-deep non
      uniformity that is reduced with age supports this theory. Similar patellar tendon
      non-uniformity has been observed, but the effects of age and sex have yet to be
      assessed. Healthy adults (n = 50, 25M/25F) from a broad range of ages (23-80)
      were recruited and non-uniformity was quantified using ultrasound speckle
      tracking during passive knee extension. Significant superficial-to-deep non
      uniformity and proximal/distal variations were observed. No effect of age was
      found, but males exhibited significantly greater non-uniformity than females (p <
      0.05). The results contrast with previous findings in the Achilles tendon; in
      this study, tendons and tendon regions at high risk for tendinopathy (i.e. males
      and proximal regions, respectively) exhibited greater non-uniformity, whereas
      high-risk Achilles tendons (i.e. older adults) previously showed reduced non
      uniformity. This suggests that non-uniformity may be dominated by factors other
      than fascicle-sliding. Anatomically, the varied proximal attachment of the
      patellar tendon may influence non-uniformity, with quadriceps passive resistance
      limiting superficial tendon movement, thus linking flexibility, non-uniformity
      and injury risk. This study also provides evidence of a differential effect of
      aging on the patellar tendon compared with evidence from prior studies on other
      tendons necessitating further study to elucidate links between non-uniformity and
      injury.

PMID- 30224167
TI  - Autologous fat grafting after sarcoma surgery: Evaluation of oncological safety.
AB  - BACKGROUND: The regenerative effectiveness of lipoaspirate procedures relies on
      the presence of mesenchymal stem cells, but the stromal microenvironment and
      hormonal secretions of the adipose tissue may be involved in cancer growth. Only
      few oncological outcome studies of fat grafting at the surgical site of malignant
      neoplasms of mesenchymal origin are available; none of these studies examined a
      series of sarcoma cases. OBJECTIVES: We analyzed outcome in terms of local or
      distant spread and overall survival to investigate the oncological safety of fat
      grafting in patients with sarcoma. PATIENTS AND METHODS: Sixty consecutive
      patients who had undergone 143 fat grafting procedures after surgical resection
      of bone and soft tissue sarcomas of the head, trunk, and limbs with clear
      resection margins were enrolled from 2004 to 2015 in our tertiary care center. A
      multidisciplinary sarcoma team administered adjuvant therapies. Patients were
      recurrence free at fat grafting. RESULTS: The overall median follow-up was 7.5
      years. At follow-up after fat grafting (2.4 years), one patient had distant
      metastasis and two had local relapse. Kaplan-Meier analysis showed disease-free
      survival rate of 95.4% (CI: 89.1-100.0) at 24 months. The risk of local
      recurrence (LR) within 24 months was 4.6% (CI: 0.0-20.9). The probability of not
      having LR after fat grafting was >= 89.1%. CONCLUSION: We found no evidence of an
      increased cancer risk after fat grafting procedures in patients with sarcoma, but
      a stimulatory role of fat cannot be excluded for bone sarcomas based on the cases
      reported here, and further studies are therefore needed.

PMID- 30224168
TI  - Multimodality imaging of the anomalous origin of the right pulmonary artery from
      the ascending aorta in an adult (hemitruncus arteriosus).
AB  - Anomalous origin of the pulmonary artery branches is a rare phenomenon. We
      describe a case of an adult with anomalous origin of the right pulmonary artery
      (hemitruncus arteriosus) associated with patent ductus arteriosus. Non-invasive
      imaging studies played an important role in the diagnosis and follow-up.
      Angiography allowed to determine the severity of pulmonary hypertension. He
      underwent surgical closure of patent ductus arteriosus, redirection of right
      pulmonary artery and atrioseptostomy with decrease of the pulmonary pressure in
      the follow-up. A high index of clinical suspicion of this entity is required in
      adults with heart failure, recurrent hemoptysis and pulmonary hypertension,
      because it could go unnoticed.

PMID- 30224169
TI  - TRP channels as potential targets for antischistosomals.
AB  - Ion channels are membrane protein complexes that underlie electrical excitability
      in cells, allowing ions to diffuse through cell membranes in a regulated fashion.
      They are essential for normal functioning of the neuromusculature and other
      tissues. Ion channels are also validated targets for many current anthelmintics,
      yet the properties of only a small subset of ion channels in parasitic helminths
      have been explored in any detail. Transient receptor potential (TRP) channels
      comprise a widely diverse superfamily of ion channels with important roles in
      sensory signaling, regulation of ion homeostasis, organellar trafficking, and
      other functions. There are several subtypes of TRP channels, including TRPA1 and
      TRPV1 channels, both of which are involved in, among other functions, sensory,
      nociceptive, and inflammatory signaling in mammals. Several lines of evidence
      indicate that TRPA1-like channels in schistosomes exhibit pharmacological
      sensitivities that differ from their mammalian counterparts and that may signify
      unique physiological properties as well. Thus, in addition to responding to TRPA1
      modulators, schistosome TRPA1-like channels also respond to compounds that in
      other organisms modulate TRPV1 channels. Notably, TRPV channel genes are not
      found in schistosome genomes. Here, we review the evidence leading to these
      conclusions and examine potential implications. We also discuss recent results
      showing that praziquantel, the current drug of choice against schistosomiasis,
      selectively targets host TRP channels in addition to its likely primary targets
      in the parasite. The results we discuss add weight to the notion that schistosome
      TRP channels are worthy of investigation as candidate therapeutic targets.

PMID- 30224170
TI  - Angioscopic Evaluation During Balloon Pulmonary Angioplasty in Chronic
      Thromboembolic Pulmonary Hypertension.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a
      progressive disorder with a poor prognosis. Recently, balloon pulmonary
      angioplasty (BPA) has been reported to be an effective treatment for inoperable
      patients with CTEPH. However, this catheter-based treatment has potentially life
      threatening vascular complications. To improve the efficacy and safety of BPA, we
      assessed the morphological evaluation of organised thrombus and the vascular
      injury by BPA procedure. METHODS: In this study, we assessed the morphology of
      organised thrombi and the vascular injury observed by angioscopy during BPA in 28
      lesions from nine CTEPH patients. RESULTS: Angioscopy visualised various forms of
      organised thrombi such as 'Mesh', 'Slit', 'Flap' and 'Mass' and allowed for a
      detailed evaluation of organised thrombus that was difficult to do by
      conventional contrast angiography. In addition, after balloon dilation for BPA,
      angioscopy revealed a haemorrhage due to a vessel wall injury caused by wiring
      and/or ballooning. CONCLUSIONS: Assessment of organised thrombus and vascular
      injury by angioscopy might contribute to improving the treatment of the patients
      with CTEPH.

PMID- 30224171
TI  - Retinal Vascular Geometry and the Prevalence of Atrial Fibrillation and Heart
      Failure in a Clinic-Based Sample.
AB  - BACKGROUND: We aimed to examine the cross-sectional association between a range
      of retinal vascular geometric variables and the prevalence of atrial fibrillation
      (AF) and heart failure. METHODS: The Australian Heart Eye Study (AHES) surveyed
      1680 participants presenting to a tertiary referral hospital for the evaluation
      of potential coronary artery disease by coronary angiography. Retinal vascular
      geometric variables (tortuosity, branching, and fractal dimension) were measured
      from retinal photographs using a computer-assisted program (Singapore I Vessel
      Assessment). Atrial fibrillation was determined based on a combination of: self
      reported history of AF; self-reported use of rate-control and anti-arrhythmic
      medications; and/or screening electrocardiogram. Self-reported echocardiography
      confirmed heart failure was also documented. RESULTS: A total of 1169
      participants had complete information on retinal vascular geometric variables and
      AF and of these 104 (8.9%) had AF. Participants in the second tertile of fractal
      dimension (Df) compared to those in the highest tertile (reference group), had
      92% increased likelihood of having AF after multivariable adjustment. A threshold
      effect for Df was identified, and participants below versus those above a Df
      threshold value of 1.472, had greater odds of having AF: multivariable-adjusted
      OR 1.85 (95% CI 1.03-3.31). Measures of retinal tortuosity and branching were not
      associated with AF. Retinal vascular geometric variables were also not associated
      with prevalence of heart failure. CONCLUSIONS: A sparser retinal microvascular
      network (lower Df) was independently associated with greater likelihood of AF.
      Further studies are needed to investigate whether temporal changes to the retinal
      vascular geometry are predictive of AF in the longer term.

PMID- 30224172
TI  - Point Shear Wave Elastography for Grading Liver Fibrosis: Can the Number of
      Measurements Be Reduced?
AB  - The aim of this study was to assess whether the number of liver point shear wave
      elastography (pSWE) measurements could be reduced compared with the currently
      recommended 10 valid measurements. Three thousand four hundred one pSWE
      examinations in patients with liver disease were performed with 10 consecutive
      valid measurements in liver segment 8. Liver fibrosis grading using published
      cutoff values were compared retrospectively using the median of 10 versus the
      first 1-9 measurements with Kendall's tau coefficient. Overall and binary
      (clinically significant [>=F2] versus non-significant [F0/F1]) fibrosis grading
      highly correlated when using 5-9 versus 10 valid measurements (tau = 0.96/0.95, p
      < 0.001). With the use of 5 valid measurements, a change in binary grading was
      observed in 87 of 3401 (2.6%) exams and only when velocities measured between 1.1
      and 1.5 m/s. Therefore, using 5-9 valid measurements in pSWE of the liver results
      in a small portion of liver fibrosis grading misclassifications compared with use
      of 10 measurements and could help decrease scanning time, cost and discomfort in
      sonographers and patients.

PMID- 30224173
TI  - Generalized myoclonus after ingestion of aldicarb as suicide attempt.

PMID- 30224174
TI  - A people-centred health workforce in Europe: How to make it happen?

PMID- 30224175
TI  - Interspecies chimeric livers: A step closer to solving the problem of
      transplantable organ shortage?

PMID- 30224176
TI  - Mid-term follow-up after surgical treatment of fragility fractures of the pelvis.
AB  - INTRODUCTION: Early operative treatment of fragility fractures of the pelvis
      (FFP) has been suggested to reduce pain and allow for earlier mobilization. The
      aim of this study was to determine mortality and functional outcome after
      operative treatment. PATIENTS AND METHODS: Patients aged >=60 years (n = 60; mean
      age 79 years, 53 female) who had operative treatment of a FFP and a follow-up of
      at least 2 years were identified and mortality was assessed using a national
      social insurance database. Those who had survived were contacted by phone and a
      modified Majeed Score was obtained. RESULTS: At final follow up (62 months,
      range, 29-117), 32 patients (53.3%) had deceased. One-year-mortality rate was
      28.3% and 2-year mortality was 36.7%. Mortality was not linked to fracture type
      (p > .05). Complications during hospitalization occurred in 26/60 patients
      (43.3%). Patients with a bilateral FFP had a longer hospitalization (18 vs. 11
      days; p = .021). The mean modified Majeed score of surviving patients was 65
      points (85.5% of achievable maximum). CONCLUSION: Mortality and in-hospital
      complications remain high among patients with FFP even when treated operatively.
      A longer hospitalization can be expected in patients with posterior bilateral
      fractures.

PMID- 30224177
TI  - Validation of a monitoring matrix for patients with brain injuries.
AB  - BACKGROUND: Brain injury is a leading cause of death and disabilities worldwide.
      The severity of brain damage is of course related to the primary injury.
      Secondary brain insults are the most powerful determinants of outcome from severe
      head injury. To improve the outcome, it needs to be well detected to be
      controlled. The detection of these factors can be difficult among numerous data.
      The objective of this work was to validate a monitoring matrix to help this
      screening. We hypothesise that a monitoring matrix will improve the detection
      rate of factors linked to secondary brain injury (SBI). METHOD: We conducted a
      single-center prospective observational simulation study. We designed a
      monitoring matrix compiling all the brain insults, intracranial data (ICP, CCP,
      PtiO2) and systemic data (PaCO2, PaO2, temperature, natremia, hemoglobin). Each
      caregiver had to analyze the same simulated data with a standard monitoring sheet
      and with the monitoring matrix. We then compared the detection rate of SBI
      factors. RESULTS: 25 caregivers analyzed a total of 265 matrixes. The monitoring
      matrix had a sensitivity of 96.5% and a specificity of 99.9% versus 69.9% and
      67.8% respectively for the standard monitoring sheet. The detection rate was
      significantly higher with the monitoring matrix (96.5%) versus the standard
      monitoring sheet (69.9%), regardless of the caregiver's status. It is also
      improved among nurses, regardless of their seniority. CONCLUSION: The use of this
      monitoring matrix is simple and inexpensive. The monitoring matrix improves
      significantly the detection rate of factors linked to secondary brain injury. It
      also provides homogenization of the detection rate among the physicians and
      nurses regardless of their experience. Nurses becoming as qualified as
      physicians, allows earlier detection and therefore a faster treatment.

PMID- 30224178
TI  - The use of suture-tape and suture-wire in arthroscopic rotator cuff repair: A
      comparative biomechanics study.
AB  - BACKGROUND: Rotator cuff repair surgery aims to create a secure, pressurized
      tendon-bone footprint to permit re-establishment of the fibrovascular interface
      and tendon healing. Flat-braided suture-tape is an alternative suture material to
      traditional suture-wire that has potential to reproduce a larger repair construct
      contact area. The objective of this study was to compare contact pressure, area
      as well as the mechanical fatigue strength between suture-wire and suture-tape
      Suture-bridge repair constructs in an ovine model. METHODS: Sixty lamb
      infraspinatus tendons were harvested and randomly allocated to three- and four
      anchor Suture-bridge repairs performed using either suture-wire or suture-tape.
      Thirty-two specimens were cyclically loaded for 200 cycles in an Instron testing
      machine, while tendon gap formation was recorded using a high speed digital
      motion analysis system. Loading to failure was then performed to evaluate
      construct ultimate tensile strength and stiffness. The remaining 28 specimens
      were assessed for repair contact pressure and area using pressure-sensitive film.
      RESULTS: There was a significantly greater average tendon contact pressure (mean
      difference: 0.064 MPa, p = 0.04) and area (mean difference: 2.71 mm2, p = 0.03)
      in fiber-tape repair constructs compared to those in fiber-wire constructs for
      the three-anchor Suture-bridge configuration. The four-anchor suture-tape
      constructs had a significantly larger ultimate tensile strength than that of the
      four-anchor suture-wire constructs (mean difference: 56.4 N, p = 0.04). There
      were no significant differences in gap formation or stiffness between suture-tape
      and suture-wire constructs (p > 0.05). CONCLUSION: Suture-tape offers greater
      pressurised tendon-bone contact than suture-wire in three-anchor Suture-bridge
      repairs, while greater mechanical strength is achieved with the use of suture
      tape in four-anchor Suture-bridge constructs.

PMID- 30224179
TI  - A single institutional experience of combined carbon-ion radiotherapy and
      chemotherapy for unresectable locally advanced pancreatic cancer.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy and safety of carbon
      ion radiotherapy (C-ion RT) for unresectable locally advanced pancreatic cancer
      (LAPC). METHODS AND MATERIALS: Patients with LAPC treated with definitive C-ion
      RT between April 2014 and July 2017 were analyzed retrospectively. The prescribed
      dose was 55.2 Gy (relative biological effectiveness [RBE] weighted absorbed dose)
      in 12 fractions. Overall survival (OS), local control (LC), progression free
      survival (PFS), and toxicity were evaluated. RESULTS: Sixty-four patients were
      enrolled. All patients completed planned course of C-ion RT. The median follow-up
      time for survivors from the initiation of C-ion RT was 24.4 months (range, 5.1
      46.1 months). Median survival time was 25.1 months. Two-year OS, LC, and PFS were
      53% (95% confidence interval [CI], 39%-66%), 82% (95% CI, 66%-91%), and 23% (95%
      CI, 14%-36%), respectively. Four patients experienced acute grade 3 toxicities
      including 3 gastrointestinal (GI) toxicities. There was no grade 3 or more late
      toxicity. CONCLUSIONS: The clinical results of C-ion RT for LAPC at our
      institution were comparable to those of a recent multi-institutional analysis.

PMID- 30224180
TI  - Science of cryopreservation in reproductive medicine - Embryos and oocytes as
      exemplars.
AB  - The modern successes of reproductive medicine are based on the achievements in
      the fields of artificial fertilization and cryobiology over the last 50years.
      Cryopreservation of oocytes makes it possible to preserve their reproductive
      potential after surgical interventions, treatment of cancer, for delayed
      pregnancy and to use cells for donation. Cryopreservation of embryos allows not
      only to reduce the multiple pregnancies rate and to increase the cumulative
      pregnancy rate as a result of embryo transfer in the following favorable cycles
      of the patient, but is also a necessary procedure in case of genetic diagnosis or
      in the case of contraindications for embryo transfer in the stimulated cycle due
      to possible complications. However, the viability of cryopreserved oocytes and
      embryos depends on the degree of their cryo damage during the process of freeze
      warming. In this regard, it is very important to develop such freezing protocols
      that minimize the damages caused by the intra- and extracellular ice crystal
      formation, toxic effect of high concentrations of cryoprotectants and osmotic
      stresses. The effectiveness of cryopreservation of gametes and embryos is
      assessed on the basis of morphological, functional and genetic changes in the
      cells after warming. Special attention should be paid to the ethical issues of
      assisted reproductive technology, including cryobiotech technologies, which in
      many countries remain open and in need of settlement.

PMID- 30224181
TI  - Separating and Segregating the Human Mitochondrial Genome.
AB  - Cells contain thousands of copies of the mitochondrial genome. These genomes are
      distributed within the tubular mitochondrial network, which is itself spread
      across the cytosol of the cell. Mitochondrial DNA (mtDNA) replication occurs
      throughout the cell cycle and ensures that cells maintain a sufficient number of
      mtDNA copies. At replication termination the genomes must be resolved and
      segregated within the mitochondrial network. Defects in mtDNA replication and
      segregation are a cause of human mitochondrial disease associated with failure of
      cellular energy production. This review focuses upon recent developments on how
      mitochondrial genomes are physically separated at the end of DNA replication, and
      how these genomes are subsequently segregated and distributed around the
      mitochondrial network.

PMID- 30224182
TI  - Translation Links Nutrient Availability with Inflammation.
AB  - Translation plays a crucial role in shaping the proteome during adaptation to
      various types of stress. A recent study by Gameiro and Struhl identified an
      inflammatory response which comprises coordination of transcriptional and
      translational programs, and which appears to be required for recovery from
      nutrient deprivation.

PMID- 30224183
TI  - A short geriatric assessment tool for the older person with cancer in India
      Development and psychometric validation.
AB  - INTRODUCTION: With rise in incidence and prevalence of cancers in the ageing
      population, the need for an age sensitive comprehensive assessment measure has
      been felt. Comprehensive Geriatric Assessment (CGA) is often difficult to
      implement due to time and logistic constraints. A brief assessment tool
      encompassing the specific domains of the CGA would be a better way to assess
      older adults with cancer. These tools exist but have not necessarily been
      culturally adapted. The main aim of the study was to develop a culturally
      relevant short geriatric assessment tool and explore its psychometric properties.
      METHODOLOGY: An initial item pool was formed after review of the literature and
      study of the existing scales. This draft tool was then pre and pilot tested to
      finalize the items and check the feasibility of application. The final tool was
      validated by exploratory factor analysis on a sample of 100 older patients with
      cancer. RESULTS: After pre and pilot study on fifteen and thirty older patients
      with cancer respectively, this tool consisting of a total of 38 items spread over
      eight domains was developed and validated on a sample of 100 subjects. Due to co
      linearity, three items were deleted after exploratory factor analysis, bringing
      the final item number to35. The Cronbach's alpha was 0.93 and the intra-class
      correlation co-efficient (ICC) was 0.94. Thus, the final tool had 13 questions
      with sub-parts (35 items in total). The time taken to administer the tool was
      around 25 min. CONCLUSION: The tool developed is valid and reliable and can be
      used for the initial assessment and further care planning of older Indian
      patients with cancer.

PMID- 30224184
TI  - Predicting chemotherapy toxicity in older adults: Comparing the predictive value
      of the CARG Toxicity Score with oncologists' estimates of toxicity based on
      clinical judgement.
AB  - AIM: The Cancer and Aging Research Group's (CARG) Toxicity Score was designed to
      predict grade >=3 chemotherapy-related toxicity in adults aged >=65 yrs.
      commencing chemotherapy for a solid organ cancer. We aimed to evaluate the CARG
      Score and compare it to oncologists' estimates for predicting severe chemotherapy
      toxicity in older adults. METHODS: Patients aged >=65 yrs. starting chemotherapy
      for a solid organ cancer had their CARG Score (range 0-23) calculated. Their
      treating oncologist, blinded to these results, independently estimated each
      patient's risk of severe chemotherapy toxicity (0-100%). Toxicities were captured
      prospectively. The predictive value of the CARG Score and oncologists' estimates
      was estimated using logistic regression and in terms of Area Under the Receiver
      Operating Characteristic curve (AU-ROC). RESULTS: 126 patients from ten
      oncologists at two sites participated. The median age was 72 yrs. (range 65-84).
      The median CARG Score was 7 (range 0-17); the median oncologist estimate of risk
      was 30% (range 3-80%), and these measures were not correlated (r = -0.01). 64
      patients (52%) experienced grade >= 3 toxicity. Rates of severe toxicity in low-,
      intermediate-, and high-risk groups by CARG Score were 58%, 47%, and 58%
      respectively, and 63%, 44%, and 67% by oncologist estimate. Severe chemotherapy
      toxicity was not predicted by the CARG Score (OR 1.04, 95%CI 0.92-1.18, p = .54,
      AU-ROC 0.52), or oncologists' estimates (OR 1.00, 95%CI 0.98-1.02, p = .82, AU
      ROC 0.52). CONCLUSION: Neither the CARG Score, nor oncologists' estimates based
      on clinical judgement, predicted severe chemotherapy-related toxicity in our
      population of older adults with cancer. Methods to improve risk prediction are
      needed.

PMID- 30224185
TI  - Value of anterosuperior rotator cuff and labral tears at MRI for predicting long
      head of biceps tearing at arthroscopy.
AB  - AIM: To determine whether magnetic resonance imaging (MRI) signs of subscapularis
      (SBT), supraspinatus (SST), or superior labral tearing predict long head of
      biceps (LHB) tendon tearing at arthroscopy. MATERIALS AND METHODS: Subjects with
      MRI studies followed by arthroscopy were collected. Radiologists graded rotator
      cuff (RC) tendons and the superior labrum using three grade classifications and
      blinded to arthroscopy. Correlation between imaging variables and surgical
      outcome was expressed in terms of odds ratios and determined using a stepwise
      logistic regression model. RESULTS: Selection criteria identified 89
      participants. Statistically significant increase in odds of finding a partial LHB
      tendon tear at arthroscopy were noted for both MRI readers with any SBT tear
      (OR=4.1-5.6, p<0.0001 to 0.002), full-thickness SST (OR=8-20.4, p=0.002 to
      0.006), and combined SST-SBT tears (OR=5.1-7.6, p<0.0001 to 0.002) and relative
      to grade 0 MRI scores for those categories. Statistically significant increase in
      the odds of finding any LHB tendon tear at arthroscopy were noted for both MRI
      readers with any SBT tear (OR=9.6 to 14.6, p<0.0001), full-thickness SST (OR=9.0
      to 52.0, p<0.0001 to 0.0004) and combined SST-SBT tears (OR=8.2 to 15.1,
      p<0.0001) at MRI and relative to grade 0 MRI scores for these categories. No
      significant predictive effect was found for the labral categories. CONCLUSION:
      LHB tendons should be closely scrutinised if anterosuperior rotator cuff tears,
      and SBT tears in particular, are found on MRI.

PMID- 30224186
TI  - Chemoembolisation with polyvinyl alcohol for advanced hepatocellular carcinoma
      with portal vein tumour thrombosis and arterioportal shunts: efficacy and
      prognostic factors.
AB  - AIM: To evaluate the efficacy and to identify prognostic factors of polyvinyl
      alcohol (PVA) chemoembolisation for treating advanced hepatocellular carcinoma
      (HCC) with portal vein (PV) tumour thrombosis (PVTT) and arterioportal shunts.
      MATERIALS AND METHODS: The clinical data of 145 advanced HCC patients with PVTT
      and arterioportal shunts were collected. The patients were divided into two
      groups: group A, with main PV invasion, (n=56) and group B, with PV branch
      invasion, (n=89). Based on arterioportal shunt types, different particle sizes of
      PVA were used for chemoembolisation. The overall survival (OS), time to
      progression (TTP), and postoperative complications were analysed retrospectively.
      RESULTS: The median OS of all patients was 10.1 months. The median OS of group A
      and group B was 8.2 and 12.5 months, respectively (chi2=6.03, p=0.01). The
      overall 6-, 12-, and 18-month survival rates of groups A and B were 63.8%, 24.9%,
      and 6.3%, and 78.1%, 55.2%, and 23.7%, respectively. After embolisation, there
      were two cases of acute liver failure and three cases of upper gastrointestinal
      bleeding. Cox multivariate survival analysis revealed that main PVTT (HR [hazard
      ratio]=1.75, p=0.01), Child-Pugh B class (HR=1.99, p=0.003) and tumour burden
      >=50% (HR=3.25, p<0.001) were independent risk factors. A dose of oxaliplatin
      >100 mg (HR=0.48, p<0.001) was an independent protection factor. CONCLUSION:
      Treatment of advanced HCC with PVTT and arterioportal shunts by PVA
      chemoembolisation is safe and effective. The patients achieved a better prognosis
      with the dose of oxaliplatin >100 mg, while main PVTT, Child-Pugh B class, and
      tumour burden >=50% were poor prognostic indicators.

PMID- 30224187
TI  - Evaluation of posterior nutcracker phenomenon using multisection spiral CT.
AB  - AIM: To prospectively evaluate the epidemiological, anatomical classification,
      clinical importance, and radiological features of posterior nutcracker phenomenon
      (PNP) in patients examined with multisection spiral computed tomography (MSCT).
      MATERIAL AND METHODS: Patients who underwent abdominal enhanced MSCT from January
      2012 to July 2016 were evaluated retrospectively. Combined with the blood, normal
      biochemistry, and urine tests, patients were assessed retrospectively for renal
      vein diameter measurements, the compression ratio of blood vessels, gender
      differences, anatomical classification, percentage of proteinuria and haematuria,
      and clinical symptoms. RESULTS: The study included 6,225 consecutive patients,
      PNP was observed in 2.06% involving the CLRV in 1.22% and retro-aortic left renal
      vein in 0.84%. The proportion of posterior nutcracker syndrome (PNS) was lower in
      PNP (17.2%). There was no difference by sex and age in the prevalence of PNP
      (p>0.05). In patients with urological symptoms, the number of type II
      abnormalities was more frequent than type Ia and type Ib abnormalities.
      Meanwhile, the number of type II abnormalities was frequent than the other two
      types. There was a significant difference between PNS and asymptomatic PNP (aPNP)
      in all measured values (p<0.001), the ratio was >4, especially in type II
      abnormalities (ratio >5.0). CONCLUSIONS: PNP is a type of left renal vein
      entrapment. It is exceptionally rare and might be underdiagnosed. MSCT and
      measured values can be useful in diagnosis and recognition.

PMID- 30224188
TI  - Life-support tools for improving performance of the Surviving Sepsis Campaign
      Hour-1 bundle.

PMID- 30224189
TI  - Production of bio-hydrogen from dairy wastewater using pretreated landfill
      leachate sludge as an inoculum.
AB  - Bio-hydrogen production from wastewater using sludge as inoculum is a sustainable
      approach for energy production. This study investigated the influence of initial
      pH and temperature on bio-hydrogen production from dairy wastewater using
      pretreated landfill leachate sludge (LLS) as an inoculum. The maximum yield of
      113.2 +/- 2.9 mmol H2/g chemical oxygen demand (COD) (12.8 +/- 0.3 mmol H2/g
      carbohydrates) was obtained at initial pH 6 and 37  degrees C. The main products
      of volatile fatty acids were acetate and butyrate with the ratio of
      acetate:butyrate was 0.4. At optimum condition, Gibb's free energy was estimated
      at -40 kJ/mol, whereas the activation enthalpy and entropy were 65 kJ/mol and
      0.128 kJ/mol/l, respectively. These thermodynamic quantities suggest that bio
      hydrogen production from dairy wastewater using pretreated LLS as inoculum was
      effective and efficient. In addition, genomic and bioinformatics analyses were
      performed in this study.

PMID- 30224190
TI  - Anomalous cell migration triggers a switch to deviation from the undifferentiated
      state in colonies of human induced pluripotent stems on feeder layers.
AB  - Understanding the fundamental mechanisms that trigger deviation from the
      undifferentiated state of human induced pluripotent stem cells (hiPSCs) provides
      key strategies to maintain their undifferentiated state during cell expansion. We
      assessed deviation from the undifferentiated state in hiPSC colonies by measuring
      cell migration rates in colonies with deviation that were targeted by the end of
      culture, in a backward manner. Analyses of migration rates of single cells in
      colonies with deviation demonstrated that the distribution of migration rates at
      the region with occurrence of deviated cells had a broad or narrow range compared
      with those at the regions of undifferentiated cells. It was found that deviated
      cells in hiPSC colonies accidentally occurred consequent to the appearance of
      relatively fast or slow migrating cells at the peripheral or central region of
      colonies, reflecting disorders owing to cell migration anomalies in the hiPSC
      colony. Fluorescence microscopy for F-actin, paxillin, and E-cadherin clarified
      the localization of integrin-mediated and cadherin-mediated adhesions,
      introducing the concept that the occurrence and pattern of deviation in a colony
      were responsive to changes of cell migration in that colony. Furthermore, a major
      component of the nuclear lamina, laminA/C displayed a rim at the nuclear
      periphery in the regions with occurrence of deviated cells, concomitant with the
      actin cytoskeleton associated with integrin- and cadherin-mediated cell adhesion.
      These results showed that an anomaly of cell migration in hiPSC colonies led to
      the accidental appearance of deviated cells therein through alternation of the
      nuclear lamina and imbalance between cell-cell and cell-substrate interactions.

PMID- 30224191
TI  - More on the pacemaker ECG in severe hyperkalemia.

PMID- 30224192
TI  - Benefits and Risks of Therapeutic Cannabinoids for Neurologic Disorders.

PMID- 30224193
TI  - Pharmacokinetics of Single-dose Ertugliflozin in Patients With Hepatic
      Impairment.
AB  - PURPOSE: Ertugliflozin, an oral, highly selective inhibitor of the sodium-glucose
      cotransporter 2, is approved in the United States and the European Union for the
      treatment of adults with type 2 diabetes mellitus. Hepatic impairment may affect,
      to varying degrees, the absorption, metabolism, and excretion of drugs and may be
      associated with a lower plasma protein binding compared with that in healthy
      individuals. This study was conducted to assess the effect of hepatic impairment
      on the pharmacokinetic (PK), safety, and tolerability profiles of ertugliflozin
      after administration of a single, 15-mg oral dose. METHODS: This was a Phase I,
      open-label, single-dose study in healthy individuals (n = 8) and those with
      moderate hepatic impairment (n = 8). Eligible participants were men or women aged
      18 to 75years with a body mass index of 18.0 to 40.5 kg/m2. Healthy individuals
      had normal hepatic function; patients with hepatic impairment had a Child-Pugh
      score of 7 to 9 points (moderate hepatic impairment). Blood samples were
      collected before dosing and during 96hours after dosing for evaluation of PK
      parameters. Adverse events were monitored throughout the study. FINDINGS: The
      adjusted least squares geometric meanratios for total ertugliflozin AUC0-infinity
      and Cmax inpatients with moderate hepatic impairment comparedwith healthy
      individuals were 87.4% (90% CI, 68.1%-112.2%) and 78.7% (90% CI, 65.7%-94.2%),
      respectively. The AUC0-infinity and Cmax for unbound ertugliflozin were also
      similar between patients with moderate hepatic impairment and healthy
      individuals. Mean half-life estimates for ertugliflozin were similar (14.6vs 13.8
      hours) in patients with moderate hepatic impairment and healthy individuals. The
      number of participants with all-causality treatment-emergent adverse events was
      similar for both groups (2 of 8 patients with moderate hepatic impairment and 3
      of 8 healthy individuals). IMPLICATIONS: Moderate hepatic impairment had no
      clinically relevant effect on the PK and safety profiles of ertugliflozin. The
      results of this study support a recommendation for no dose adjustment of
      ertugliflozin in patients with mild or moderate hepatic impairment. Ertugliflozin
      was well tolerated when administered tohealthy individuals and patients with
      moderate hepatic impairment. ClinicalTrials.gov identifier: NCT02115347.

PMID- 30224194
TI  - Re: Henk G. van der Poel, Roderick C.N. van den Bergh, Erik Briers, et al. Focal
      Therapy in Primary Localised Prostate Cancer: The European Association of Urology
      Position in 2018. Eur Urol 2018;74:84-91.

PMID- 30224195
TI  - A Nomogram to Predict Significant Estimated Glomerular Filtration Rate Reduction
      After Robotic Partial Nephrectomy.
AB  - BACKGROUND: Decreased functional outcome after partial nephrectomy is associated
      with overall mortality. OBJECTIVE: To create a model that predicts >=25%
      reduction from baseline estimated glomerular filtration rate (eGFR) in patients
      undergoing robot-assisted partial nephrectomy (RAPN) and to investigate the role
      of acute kidney injury (AKI) in this patient population. DESIGN, SETTING, AND
      PARTICIPANTS: A total of 999 patients were identified from a multi-institutional
      database. Renal function was defined according to the Kidney Disease: Improving
      Global Outcomes (KDIGO) guidelines for chronic kidney disease (CKD). AKI was
      defined as >25% reduction in eGFR from pre-RAPN period to discharge. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram to predict significant eGFR
      reduction (>=25% from baseline) in the time-frame between 3 and 15mo after RAPN
      was built based on the coefficients of Cox survival function that ultimately
      included age, sex, Charlson comorbidity index, baseline eGFR, RENAL nephrometry
      score, AKI in patients with normal baseline renal function, and AKI on CKD. Such
      landmark analysis was chosen in order to account for eGFR fluctuations occurring
      within the first 3mo of RAPN. The proportional hazard assumption was evaluated
      through the Schonfeld test. Internal validation was performed using the leave-one
      out cross validation. Calibration was graphically investigated. The decision
      curve analysis (DCA) was used to evaluate the net clinical benefit. RESULTS AND
      LIMITATIONS: Median (interquartile range [IQR]) age at surgery was 61yr (51, 68).
      Overall, 146 patients experienced significant eGFR reduction; median follow-up
      for survivors was 12.4mo. The 15-mo probability of significant eGFR reduction was
      19%. All variables fitted into the model, including AKI in patients with normal
      renal function (hazard ratio [HR]: 4.51; 95% confidence interval [CI]: 3.12,
      6.60; p<0.001) and AKI on CKD (HR: 4.90; 95% CI: 2.17, 11.1; p<0.001), emerged as
      predictors of significant eGFR reduction (all p<=0.048) and were considered to
      build a nomogram. The internally validated c index was 73%. The model
      demonstrated excellent calibration and a net benefit at the DCA with
      probabilities >=4%. CONCLUSIONS: We developed a nomogram that accurately predicts
      significant eGFR reduction after RAPN. This model may serve as a tool for early
      identification of patients at high risk for significant renal function decline
      after surgery. PATIENT SUMMARY: We have developed a model for the prediction of
      renal function loss after partial nephrectomy for renal cancer.

PMID- 30224196
TI  - Reply to Jeffrey Graham, Omar Abdel-Rahman, Toni K. Choueiri, and Daniel Y.C.
      Heng's Letter to the Editor re: Fabio Conforti, Laura Pala, Vincenzo Bagnardi, et
      al. Cancer Immunotherapy Efficacy and Patients' Sex: A Systematic Review and Meta
      analysis. Lancet Oncol 2018;19:737-46: Outcomes of Metastatic Renal Cell
      Carcinoma by Gender: Contrasting Results from the International mRCC Database
      Consortium.

PMID- 30224197
TI  - "Real-world" Practice Makes Perfect: Ensuring the Active Component of Active
      Surveillance for Prostate Cancer.

PMID- 30224198
TI  - Child welfare system interventions on behalf of children and families:
      Highlighting the role of court appointed special advocates.
AB  - Nearly three-quarters of a million children are victims of abuse and neglect in
      the United States every year. This article describes the scope of the problem and
      explains how the child welfare system intervenes, including how cases are
      reported, how Child Protective Services (CPS) assesses the risk, how CPS
      determines when in-home services are appropriate or if a child should be removed
      from the home, how ongoing cases are managed, and the options for permanency for
      children in the system. The article also explains how the Family Court system
      operates as the decision-maker in child abuse and neglect cases and discusses the
      various models of legal representation provided to child victims, depending on
      the jurisdiction in which they live. The authors document how outcomes for child
      victims of abuse and neglect are greatly improved when their representation
      includes the appointment of a Court Appointed Special Advocate (CASA Volunteer)
      to advocate for their best interests. The history of the CASA model is outlined,
      and the structure of the current program, which includes over 76,000 volunteers
      in nearly 1000 local programs in 49 states, is described. This article explains
      the CASA methodology and how this intervention improves outcomes for abused and
      neglected children. The authors argue that greater public and private support
      would provide more local CASA agencies with the resources to recruit, train, and
      support more CASA Volunteers to help more child victims of abuse and neglect.

PMID- 30224199
TI  - Immunogenicity and safety of MF59-adjuvanted and full-dose unadjuvanted trivalent
      inactivated influenza vaccines among vaccine-naive children in a randomized
      clinical trial in rural Senegal.
AB  - INTRODUCTION: Effective, programmatically suitable influenza vaccines are needed
      for low-resource countries. MATERIALS AND METHODS: This phase II, placebo
      controlled, randomized safety and immunogenicity trial (NCT01819155) was
      conducted in Senegal using the 2012-2013 Northern Hemisphere trivalent influenza
      vaccine (TIV) formulation. Participants were allocated in a 2:2:1 ratio to
      receive TIV (full-dose for all age groups), adjuvanted TIV (aTIV), or placebo.
      Participants were stratified into age groups: 6-11, 12-35, and 36-71 months. All
      participants were vaccine-naive and received two doses of study vaccine 4 weeks
      apart. The two independent primary objectives were to estimate the immunogenicity
      of TIV and of aTIV as the proportion of children with a hemagglutination
      inhibition (HI) antibody titer of >=1:40 to each vaccine strain at 28 days post
      dose two. Safety was evaluated by solicited local and systemic reactions,
      unsolicited adverse events, and serious adverse events. RESULTS: 296 children
      received TIV, aTIV, or placebo, and 235 were included in the final analysis.
      After two doses, children aged 6-11, 12-35, and 36-71 months receiving TIV had HI
      titers >=1:40 against A/H1N1 (73.1%, 94.1%, and 97.0%), A/H3N2 (96.2%, 100.0%,
      and 100.0%), and B (80.8%, 97.1%, and 97.0%), respectively. After two doses, 100%
      children aged 6-11, 12-35, and 36-71 months receiving aTIV had >=1:40 titers
      against A/H1N1, A/H3N2, and B. After a single dose, the aTIV response was
      comparable to or greater than the TIV response for all vaccine strains. TIV and
      aTIV reactogenicity were similar, except for mild elevation in temperature (37.5
      38.4  degrees C) which occurred more frequently in aTIV than TIV after each
      vaccine dose. TIV and aTIV had similarly increased pain/tenderness at the
      injection site compared to placebo. CONCLUSIONS: Both aTIV and full-dose TIV were
      well-tolerated and immunogenic in children aged 6-71 months. These vaccines may
      play a role in programmatically suitable strategies to prevent influenza in low
      resource settings.

PMID- 30224200
TI  - Directed selection of amino acid changes in the influenza hemagglutinin and
      neuraminidase affecting protein antigenicity.
AB  - Influenza virus hemagglutinin (HA) and neuraminidase (NA) proteins elicit
      protective antibody responses and therefore, are used as targets for vaccination,
      especially the HA protein. However, these proteins are subject to antigenic
      drift, decreasing vaccine efficacy, and few to no studies have analyzed antigenic
      variability of these proteins by growing the viruses under immune pressure
      provided by human sera. In this work, we show that after growing different
      influenza virus strains under immune pressure, the selection of amino acid
      changes in the NA protein is much more limited than the selection in the HA
      protein, suggesting that the NA protein could remain more conserved under immune
      pressure. Interestingly, all the mutations in the HA and NA proteins affected
      protein antigenicity, and many of the selected amino acid changes were located at
      the same positions found in viruses circulating. These studies could help to
      inform HA and NA protein residues targeted by antibody responses after virus
      infection in humans and are very relevant to update the strains used for
      influenza virus vaccination each year and to improve the currently available
      vaccines.

PMID- 30224201
TI  - Potential for HPV vaccination and primary HPV screening to reduce cervical cancer
      disparities: Example from New Zealand.
AB  - BACKGROUND: Cervical cancer rates are over twice as high, and screening coverage
      is lower, in Maori women compared to other women in New Zealand, whereas uptake
      of HPV vaccine is higher in Maori females. We aimed to assess the impact of HPV
      vaccination and the proposed transition to 5-yearly primary HPV screening in
      Maori and other women in New Zealand, at current participation levels; and
      additionally to investigate which improvements to participation in Maori females
      (in vaccination, screening, or surveillance for screening-defined higher-risk
      women) would have the greatest impact on cervical cancer incidence/mortality.
      METHODS: An established model of HPV vaccination and cervical screening in New
      Zealand was adapted to fit observed ethnicity-specific data. Ethnicity-specific
      models were used to estimate the long-term impact of vaccination and screening
      (vaccination coverage 63% vs 47%; five-year screening coverage 68% vs 81% in
      Maori vs European/Other women, respectively). RESULTS: Shifting from cytology to
      HPV-based screening is predicted to reduce cervical cancer incidence by 17% (14%)
      in Maori (European/Other) women, respectively. The corresponding reductions due
      to vaccination and HPV-based screening combined were 58% (44%), but at current
      participation levels long-term incidence would remain almost twice as high in
      Maori women (6.1/100,000 compared to 3.1/100,00 in European/Other women). Among
      strategies we examined, the greatest impact came from high vaccine coverage and
      achieving higher attendance by Maori women under surveillance for screen-detected
      abnormalities. CONCLUSION: Relative reductions in cervical cancer due to
      vaccination and HPV-based screening are predicted to be greater in Maori than in
      European/Other women. While these interventions have the potential to
      substantially reduce between-group differences, cervical cancer incidence would
      remain higher in Maori women. These findings highlight the importance of multiple
      approaches and the potential influence of factors beyond HPV prevention.

PMID- 30224202
TI  - Guidelines for Clinical Target Volume Definition for Perineural Spread of Major
      Salivary Gland Cancers.
AB  - AIMS: Postoperative radiotherapy is the standard of care for resected major
      salivary cancers that are at risk of locoregional recurrence. Of the various
      histological subtypes, perineural invasion is most common in adenoidcystic
      carcinomas of the three major salivary glands - parotid, submandibular and
      sublingual. The clinical target volume (CTV) for these cases must include the
      relevant cranial nerve pathways at risk. A contouring atlas was devised for
      delineation of the CTV of the nerves supplying the major salivary glands.
      MATERIALS AND METHODS: Using standard anatomy texts and e-anatomy sources the
      nerves supplying the major salivary glands were identified. Subsequently the
      pathways of the nerves were drawn on an archived patient's planning computed
      tomography scan. RESULTS: The innervation of the major salivary glands has been
      identified and studied. Both bone and soft tissue CTVs have been delineated. A
      full set of images and CTVs of all the relevant transverse computed tomography
      slices has been archived, a number of which are printed in this article.
      CONCLUSIONS: Variation in CTV delineation is a recognised problem in a variety of
      anatomic sites. Guidelines and atlases can standardise practice and may improve
      the safety and efficacy of therapy. An atlas has been generated to guide
      clinicians in delineating the CTVs for perineural spread in major salivary gland
      cancers.

PMID- 30224203
TI  - Delivering Functional Imaging on the MRI-Linac: Current Challenges and Potential
      Solutions.
AB  - Magnetic resonance imaging (MRI) is a highly versatile imaging modality that can
      be used to measure features of the tumour microenvironment including cell death,
      proliferation, metabolism, angiogenesis, and hypoxia. Mapping and quantifying
      these pathophysiological features has the potential to alter the use of adaptive
      radiotherapy planning. Although these methods are available for use on diagnostic
      machines, several challenges exist for implementing these functional MRI methods
      on the MRI-linear accelerators (linacs). This review considers these challenges
      and potential solutions.

PMID- 30224204
TI  - The Road Map for Proton Therapy: Reply to Professor Karol Sikora.

PMID- 30224205
TI  - Assessing mercury contamination patterns of fish communities in the Laurentian
      Great Lakes: A Bayesian perspective.
AB  - We examine the spatio-temporal trends of mercury, a well-known global legacy
      contaminant, in eleven fish species across all of the Canadian Great Lakes. These
      particular fish species are selected based on their ecological, commercial, and
      recreational importance to the biodiversity and fishing industry of the Great
      Lakes. We present a two-pronged Bayesian methodological framework to rigorously
      assess mercury temporal trends across multiple fish species and locations. In the
      first part of our analysis, we develop dynamic linear models to delineate the
      total mercury levels and rates of change, while explicitly accounting for the
      covariance between fish length and mercury levels in fish tissues. We then use
      hierarchical modelling to evaluate the spatial variability of mercury
      contamination between nearshore and offshore locations, as well as to examine the
      hypothesis that invasive species have induced distinct shifts on fish mercury
      contamination trends. Our analysis suggests that the general pattern across the
      Great Lakes was that the elevated mercury concentrations during the 1970s had
      been subjected to a declining trend throughout the late 1980s/early 1990s,
      followed by a gradual stabilization after the late 1990s/early 2000s. The
      declining trend was more pronounced with top fish predators, whereas benthivorous
      fish species mainly underwent wax-and-wane cycles with a weaker evidence of a
      long-term declining trend. Historically contaminated regions, designated as Areas
      of Concern, and bays receiving riverine inputs are still characterized by mercury
      concentrations that can lead to consumption restrictions. Lake Erie displayed the
      lowest mercury levels across all the fish species examined. However, several
      species of commercial importance showed a reversing (increasing) trend in the
      2000s, although their current levels do not pose any major concerns for
      consumption advisories. These recent trend reversals can be linked with
      systematic shifts in energy trophodynamics along with the food web alterations
      induced from the introduction of non-native species, and the potentially
      significant fluxes from the atmosphere.

PMID- 30224206
TI  - Latissimus dorsi muscle transfer reduces external rotation deficit at the cost of
      internal rotation in reverse shoulder arthroplasty patients: a cohort study.
AB  - HYPOTHESIS: We hypothesized that treatment of rotator cuff arthropathy (RCA) with
      reverse shoulder arthroplasty (RSA) and an additional latissimus dorsi transfer
      (LDT) in patients with an active external rotation deficit (ERD) would restore
      external rotation (ER) with concomitant deterioration in internal rotation.
      METHODS: In our cohort study, 26 RCA patients with an active ERD (ie, positive
      lag sign and maximum active ER of 0 degrees ) underwent RSA between September
      2007 and February 2015; LDT was completed in 13 of these patients. In addition,
      88 control patients without ERD who underwent only RSA were identified. Clinical
      outcomes of strength, range of motion, Constant-Murley score, and Shoulder Pain
      and Disability Index score, as well as complications, were documented 6, 12, 24,
      and 60 months postoperatively. We made comparative analyses using statistical
      mixed models. RESULTS: The LDT procedure extended the surgical time by 26 minutes
      (P = .003). LDT patients had up to 22 degrees  better postoperative active ER
      than control patients (P < .001), although this was accompanied by an internal
      rotation deficit (77% vs 46% of control patients could not reach the lumbosacral
      region, P = .010). We calculated a 23% risk of local procedure-related
      complications for RSA patients with an active ERD and LDT. CONCLUSION: Patients
      with RCA and an active ERD seem to benefit from an LDT, although this is
      accompanied by the potential loss of internal rotation. This additional procedure
      is associated with an extended surgical time as well as a possible increase in
      the risk of a complication occurring.

PMID- 30224207
TI  - Outcomes of shoulder replacement in humeral head avascular necrosis.
AB  - BACKGROUND: This retrospective review evaluated 25 patients with 29 shoulders
      treated with arthroplasty for humeral head avascular necrosis (HHAVN) between
      2004 and 2015. We hypothesized that regardless of implant, radiographic stage, or
      etiology, patients would appreciate significant improvement in pain, range of
      motion, and shoulder functionality after surgical intervention. METHODS: Data
      were obtained by record review on all patients meeting inclusion criteria.
      Outcomes were evaluated using Simple Shoulder Test, Modified Constant Score,
      University of California Los Angeles Shoulder Rating Scale, and American Shoulder
      and Elbow Surgeons Standardized Shoulder Assessment Form. The data were assessed
      by all patients and subcategories (treatment, avascular necrosis stage, and
      underlying cause). RESULTS: At a mean follow-up of 3.9 years (range, 1-8.5
      years), all patients who underwent operative intervention for HHAVN showed
      statistically significant improvement in functionality measurements (P < .01).
      Patients who underwent total shoulder arthroplasty (TSA) noted higher median
      outcome scores and greater improvement in all scoring methods compared with their
      hemiarthroplasty counterparts. The high-stage disease shoulders showed similar
      trends over low-stage counterparts. The shoulders in the trauma causal group had
      the highest scores in 3 of 4 outcome measures and favorable change in all scoring
      methods. These differences were not statistically significant (P > .05). No
      revision arthroplasties were required. Minor complications (suture abscess and
      intraoperative calcar fracture requiring cabling) occurred in 2 TSA patients.
      CONCLUSIONS: Our outcomes demonstrate that in the short- to midterm follow-up,
      TSA or hemiarthroplasty is a safe and equally effective treatment for patients
      diagnosed with HHAVN regardless of etiology and radiographic staging.

PMID- 30224208
TI  - Long-term follow-up of corrective ulnar osteotomy for missed Monteggia fractures
      in children.
AB  - BACKGROUND: Pediatric Monteggia fractures are relatively rare and are commonly
      missed. Radial head subluxation can persist with long-term consequences if these
      fractures are left untreated. We evaluated the long-term treatment outcomes after
      open reduction with ulnar osteotomy for missed Monteggia fractures during
      childhood. MATERIALS AND METHODS: Fourteen children were included. Our objective
      was to assess the clinical and radiographic postoperative outcomes. We evaluated
      satisfaction by questionnaire. Open reduction of the radial head was performed,
      combined with an opening-wedge ulnar osteotomy. The mean interval between trauma
      and surgery was 26.9 months (range, 1-145 months). The mean length of follow-up
      was 132 months (range, 67-206 months). RESULTS: Only patients with a delay of
      more than 6 months complained of elbow tenderness. Clinical improvement (except
      for pronation) was obtained postoperatively, with significance found in the
      flexion-extension arc (P = .011). In addition, pronation loss (P = .044) and the
      flexion-extension arc (P = .041) improved significantly in patients with a
      surgical delay under 6 months compared with patients with a surgical delay of
      more than 6 months. Radiographically, there were 9 good and 5 fair results. We
      found a negative association between radiographic outcomes and both age at
      surgery and delay to surgery (P = .036 and P = .039, respectively). CONCLUSIONS:
      Good results can be obtained after open reduction with opening-wedge ulnar
      osteotomy. Lesser clinical and radiographic outcomes can be expected after a
      surgical delay of more than 6 months. Furthermore, the radiographic outcome seems
      better if the patient is younger than 6 years.

PMID- 30224209
TI  - [Interferon gamma release assay tests and HIV infection].

PMID- 30224210
TI  - [Interferon gamma release assay (IGRA) tests].

PMID- 30224211
TI  - [Steroids for community-acquired pneumonia: Should we go on searching or should
      we give up?]

PMID- 30224212
TI  - [Interferon gamma release assay tests in children less than 15 years old].

PMID- 30224213
TI  - [Tuberculosis contact tracing].

PMID- 30224214
TI  - [Interferon gamma release assay test in healthcare workers].

PMID- 30224215
TI  - [Practice recommendations for the use and interpretation of interferon gamma
      release assays in the diagnosis of latent and active tuberculosis].

PMID- 30224216
TI  - [Role of magnetic resonance imaging in preoperative assessement of hilar
      cholangiocarcinoma].
AB  - Magnetic resonance cholangiopancreatography is a non-invasive imaging, highly
      performant in detecting and locating biliary stenosis and in predicting its
      malignancy. The combination of two and three-dimensional MRI sequences is
      recommended to assess a biliary obstacle. Cholangiopathies are the main
      differential diagnosis of cholangiocarcinomas. In addition to bile duct
      abnormalities beyond the stenosis, the predictive signs of malignancy are:
      asymmetric irregular luminal narrowing (longer than 3mm and thicker than 13mm),
      abrupt discontinuation of stenosis, and enhancement superior to that of the
      adjacent hepatic parenchyma during arterial and portal acquisitions. Diffusion
      sequences improve the sensitivity of biliary stenosis detection. Moreover,
      restriction of diffusion is useful for distinguishing malignant from benign
      stenosis. Combining Magnetic resonance cholangiopancreatography, late LAVA and
      diffusion sequences improves the sensitivity of detection of a possible biliary
      extension without significant specificity. MRI with gadolinium chelate injection
      is efficient in assessing vascular extension of cholangiocarcinomas. However its
      accuracy remains lower than that of Ct-scan. To assess hepatic, lymphatic and
      peritoneal extensions of cholangiocarcinomas, it is fundamental to combine
      diffusion and dynamic MRI sequences.

PMID- 30224217
TI  - Laryngopharyngeal reflux in obstructive sleep apnoea patients: Literature review
      and meta-analysis.
AB  - PURPOSE: Laryngopharyngeal reflux (LPR) is a frequent condition in Obstructive
      Sleep Apnoea (OSA) patients and different studies have been published in the last
      years about this topic. A review of the published literature regarding LPR in OSA
      patients has been reported. A meta-analysis to evaluate the incidence of LPR in
      OSA patients and correlate LPR positivity with OSA patients' characteristics has
      been performed. METHODS: A comprehensive review of the English language
      literature about LPR in OSA patients was performed using the most important
      electronic databases (PubMed, EMBASE, the Cochrane Library etc.). A total of 10
      papers studying LPR in OSA were assessed and considered eligible for the meta
      analysis. RESULTS: The data analysis regarding 870 identified OSA patients showed
      that 394 patients were LPR +, while 476 were LPR-. The meta-analysis showed no
      statistical difference regarding the AHI value between LPR + patients and LPR-
      patients (p = 0,3). Mean BMI was more higher in LPR + patients than in the
      patients without LPR, showing a significant statistical difference (p = 0.001).
      CONCLUSION: Current international literature demonstrates a high incidence of LPR
      (45.2%) in OSA patients. The severity of AHI in OSA patients would not seem to
      correlate with the presence of laryngopharyngeal reflux. The OSA patients with
      LPR showed a higher BMI compared with LPR- patients.

PMID- 30224218
TI  - Anterior Canal benign paroxysmal positional Vertigo following surgical Management
      of superior canal dehiscence.
AB  - OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is a common post-surgical
      finding in patients managed for superior semicircular canal dehiscence (SSCD).
      The posterior semicircular canal has been reported as the involved canal in the
      majority of cases of post-surgical BPPV, with only two cases reported of lateral
      canal involvement. The objective of this report is to present a case in which an
      anterior semicircular canal BPPV response was identified in a patient following
      surgical management for SSCD. METHOD: This case report presents an adult with
      residual dizziness following surgical management of SSCD and vestibular
      rehabilitation therapy (VRT). During subsequent evaluation of vestibular
      function, a transient and torsional, down-beating nystagmus was provoked along
      with vertigo during Dix-Hallpike positioning to the right. This was consistent
      with BPPV affecting the left superior (anterior) semicircular canal. RESULTS: The
      patient was treated with a repositioning maneuver to manage anterior semicircular
      canal BPPV and no nystagmus response was recorded with post-repositioning Dix
      Hallpike test. Review of radiographic images, obtained prior to vestibular
      function testing, showed a hyperintensity in the area of the left anterior
      semicircular canal ampulla. It was felt this was likely a bone chip from the SSCD
      repair that was pushing against the ampulla with further mobile debris within the
      canal. CONCLUSION: It is reported that BPPV is a common complication in patients
      surgically managed for SSCD. Posterior semicircular canal BPPV is reported most
      often, with a couple of cases of lateral semicircular canal BPPV also reported.
      As far as we are aware, the current case represents the first report of anterior
      semicircular canal BPPV in this type of patient.

PMID- 30224219
TI  - Performance of the Bethesda system in the citopathological diagnosis of the
      thyroid nodule.

PMID- 30224220
TI  - Diffusion-weighted magnetic resonance imaging for the detection of thyroid
      cancer.
AB  - BACKGROUND: Nodular thyroid disease possesses the potential to harbor malignancy.
      Our aim was to evaluate the significance of cervical diffusion-weighted magnetic
      resonance imaging (DW-MRI) for the detection of malignant thyroid nodules.
      METHODS: Sixty-five thyroid nodules from 58 patients who had undergone surgery
      were evaluated. Preoperative parameters, demographic data, ultrasound findings,
      fine-needle aspiration biopsy results and apparent diffusion coefficient (ADC)
      values of the nodules at DW-MRI were compared with the results from postoperative
      pathology examinations. RESULTS: The "benign group" included 50 (76.9%) nodules,
      while 15 (23.1%) nodules constituted the "malignancy group". Minimum, maximum and
      mean ADC values of the nodules were significantly lower in the malignancy group
      (p < 0.05). The best cutoff value for the mean ADC value was 1.33 * 10-3 mm2/s,
      with a sensitivity of 66.67%, a specifity of 89.13%, a positive predictive value
      of 53.63% and a negative predictive value of 89.13%. A mean ADC value equal to or
      lower than 1.33 * 10-3 mm2/s was associated with 9 times higher risk of
      malignancy (odds ratio: 9.111, 95% confidence interval: 2.49-33.21). CONCLUSIONS:
      The ADC value detected by cervical DW-MRI can be considered a predictive
      parameter for the detection of thyroid cancer.

PMID- 30224221
TI  - Scenario-based simulation training as a method to increase nursing students'
      competence in demanding situations in dementia care. A mixed method study.
AB  - Dementia is a debilitating condition affecting personality, day-to-day activities
      and cognitive function, which in turn may hamper the patient's decision-making
      capacity. This challenges staff competence in ethics and legislation in order to
      enhance dignity through improved communication and avoid coercive treatment.
      Scenario-based simulation training can increase communication skills in demanding
      situations. This study aimed to explore if this also applies to nursing students
      within dementia care, and if nursing students improve their ethical reflection
      and ability to avoid the use of coercion. This was piloted in a concurrent mixed
      method design using focus groups, questionnaires and observations. Twelve
      students from the bachelor of nursing programme participated. The results showed
      that two training sessions increased the use of confidence-building approaches
      and the students became more aware of the importance of person-centred dementia
      care and the importance of knowing the patient's history, to gain the patient's
      trust. Furthermore, the students' knowledge regarding legislation concerning
      coercion increased, and they became more aware of own attitudes and documenting
      deviations from treatment. Scenario-based simulation training seems to be a
      useful approach for preparing nursing students to become more aware of demanding
      situations in dementia care and how to handle such situations.

PMID- 30224222
TI  - Parent's experiences of their child's withdrawal syndrome: a driver for
      reciprocal nurse-parent partnership in withdrawal assessment.
AB  - : Withdrawal assessment in critically ill children is complicated by the reliance
      on non-specific behaviours and compounded when the child's typical behaviours are
      unknown. The existing approach to withdrawal assessment assumes that nurses
      elicit the parents' view of the child's behaviours. OBJECTIVE AND RESEARCH
      METHODOLOGY: This qualitative study explored parents' perspectives of their
      child's withdrawal and preferences for involvement and participation in
      withdrawal assessment. Parents of eleven children were interviewed after their
      child had completed sedation weaning during recovery from critical illness. Data
      were analysed using thematic analysis. SETTING: A large children's hospital in
      the Northwest of England. FINDINGS: Parents experienced varying degrees of
      partnership in the context of withdrawal assessment and identified information
      deficits which contributed to their distress of parenting a child with withdrawal
      syndrome. Most parents were eager to participate in withdrawal assessment and
      reported instances where their knowledge enabled a personalised interpretation of
      their child's behaviours. Reflecting on the reciprocal nature of the information
      deficits resulted in the development of a model for nurse-parent collaboration in
      withdrawal assessment. CONCLUSION: Facilitating nurse-parent collaboration in
      withdrawal assessment may have reciprocal benefits by moderating parental stress
      and aiding the assessment and management of withdrawal syndrome.

PMID- 30224223
TI  - Clostridium colicanis bacteraemia in an asthmatic patient diagnosed as acute
      respiratory infection.

PMID- 30224224
TI  - Generosity and Duration of Medicaid Expansion Waivers and Access to Care.
AB  - INTRODUCTION: Prior to expansion of Medicaid under the Affordable Care Act, some
      states obtained Section 1115 waivers from the federal government that allowed
      them to expand eligibility for Medicaid to adult populations that were not
      covered previously. Expansion waivers in these states differed in their
      generosity and year of implementation, creating variation in coverage
      availability and program longevity across states. This study examined the
      association between generosity and duration of Medicaid expansion waivers and
      access to preventive services. METHODS: The 2012 Medical Expenditure Panel Survey
      data were used to estimate adjusted logistic models in 2016, comparing outcomes
      among low-income non-elderly adults living in generous (Medicaid eligibility
      threshold >=138% federal poverty level) and moderate (Medicaid eligibility
      threshold <138% federal poverty level) waiver states, relative to no-waiver
      states. RESULTS: Moderate and generous waivers were associated with statistically
      significant (p<0.001) increases in probabilities of having a usual source of care
      and a blood pressure check, relative to states without a waiver to expand. Low
      income individuals living in states with longer waiver durations had better
      access to healthcare services than a similar group living in comparison states.
      CONCLUSIONS: Not only is Medicaid waiver generosity associated with improving
      access to healthcare services, but the combination of generosity and longer
      duration of a waiver also intensifies the association. As states gain flexibility
      in designing their Medicaid programs, the healthcare benefits associated with
      both generosity and duration of waivers are important considerations for policy
      makers.

PMID- 30224225
TI  - Reassessing Urban Health Interventions: Back to the Future with Google Street
      View Time Machine.
AB  - INTRODUCTION: Validity of research linking built environments to health relies on
      the availability and reliability of data used to measure exposures. As cities
      transform, it is important to track when and where urban changes occur, to
      provide detailed information for urban health intervention research. This paper
      presents an online observation method of the implementation of traffic
      calmingfeatures using Google Street View Time Machine. The method is used to
      validate an existingadministrative database detailing the implementation of curb
      extensions and speed bumps. METHODS: Online observation of curb extensions and
      speed bumps was conducted for four boroughsin Montreal, Canada, in autumn 2016,
      and compared with administrative data documenting traffic-calming measures
      implemented between 2008 and 2014. All images available through the Time Machine
      function between 2007 and 2016 for 708 intervention sites were visualized online.
      Records in the administrative database were compared to real-world Google Street
      View observations and tested in terms of sensitivity, specificity, and positive
      predicted value. RESULTS: Google Street View Time Machine allowed the
      visualization of a median of seven different dates per street intersection and
      six dates per street segment. This made it possible to analyze built environment
      changes within 3,973 distinct time periods at 708 locations. Validation of the
      administrative data regarding presence of an intervention showed 99% (95% CI=97%,
      99%) sensitivity, 58% (95% CI=51%, 64%) specificity, and 77% (95% CI=73%, 81%)
      positive predictive value. CONCLUSIONS: Google Street View Time Machine allowed
      past (2007-2016) online documentation of microscale urban interventions-curb
      extensions and speed bumps. The proposed method offers a new way to document
      historic changes to the built environment, which will be useful for urban health
      intervention research.

PMID- 30224226
TI  - Response to Beriain.
AB  - Professor Beriain's criticism rests on a narrow conception of human dignity
      pertaining only to individuals within a society. The social relations and norms
      that underpin human dignity are treated as mere group interests that are
      secondary to the dignity of the individual. In our view, this is a false
      dichotomy.

PMID- 30224227
TI  - Biobutanol Production from Crystalline Cellulose through Consolidated
      Bioprocessing.
AB  - Biobutanol production directly from lignocellulose, known as consolidated
      bioprocessing (CBP), is expected to be much less expensive than a process where
      hydrolytic enzyme production, cellulose saccharification, and microbial
      fermentation are accomplished separately. However, few microbes possess both
      cellulolytic and solventogenic properties in nature. Current research aims to
      endow cellulolytic microorganisms with butanol-producing ability or to set up
      microbial consortia for CBP. This review comprehensively details current
      achievements attempting to confer butanol-generating ability, not only to
      cellulolytic Clostridium strains but also to microbial consortia, to address and
      overcome major challenges in butanol production from cellulose. Recent advances
      in improving cellulosome activities within cellulolytic Clostridium strains are
      also emphasized.

PMID- 30224228
TI  - What's new in the treatment of multidrug-resistant gram-negative infections?
AB  - Eradicating multi-drug resistant (MDR) organisms has been a major challenge in
      healthcare settings worldwide. Newly approved drugs and those currently in the
      pipeline may have a promising solution to this issue. The purposes of this review
      are to describe the various resistance mechanisms of Gram-negative bacteria and
      to provide a summary of the current literature available on the newer agents,
      such as ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and
      other emerging agents used for the treatment of MDR Gram-negative infections.
      Given that MDR organisms confer resistance to treatment by various methods,
      including enzymatic degradation, efflux pumps, and porin mutation, an
      understanding of mechanisms of bacterial resistance combined with information on
      newer antimicrobial agents against MDR Gram-negative bacteria will further assist
      clinicians in determining the best suitable therapy for the treatment of various
      complicated infections.

PMID- 30224229
TI  - Arthroscopy-assisted treatment of scaphoid and lunate cysts: Clinical evaluation
      of 7 cases.
AB  - Intraosseous cysts of the carpus are relatively common benign tumors. They are
      often discovered by chance and can cause wrist pain thereby requiring appropriate
      management. While conventional open surgical treatment leads to good results, it
      has certain disadvantages, the main one being postoperative stiffness.
      Arthroscopic treatment has been proposed as an alternative for lunate cysts. The
      present study consisted in evaluating the feasibility and outcomes of
      arthroscopic treatment for lunate and scaphoid cysts. The main objective was to
      evaluate the postoperative clinical outcomes at 3 and 18 months. The secondary
      objective was to evaluate the integration of a cancellous bone graft. We
      conducted a retrospective study of eight patients who underwent surgery between
      April 2010 and October 2016. Of these, four had a lunate cyst and four had a
      scaphoid cyst; all cysts had a dorsal operculum. Patients had disabling wrist
      pain that did not respond to conservative treatment. The diagnosis was confirmed
      by radiography and either a CT scan or an MRI. Curettage and cancellous grafts
      were performed under arthroscopic control. The technique was carried out
      successfully in all cases. One patient was lost to follow-up. At 18 months,
      postoperative pain was rated at 1.28 on a visual analog scale. The grip strength
      (measured with a Jamar dynanometer) was 77% when compared to the contralateral
      side. There was an improvement in joint range of motion, with an average wrist
      flexion of 67.5 degrees  compared to 48.3 degrees  preoperatively and an average
      wrist extension of 71.5 degrees  compared to 47.6 degrees  preoperatively. The
      Patient-Rated Wrist Evaluation (PRWE) score decreased from 69.7 to 12.7, which
      was a significant decrease. A good integration of the cancellous graft was
      confirmed at 6 months in all cases by CT scan or MRI. Curettage with a cancellous
      graft of lunate and scaphoid cysts under arthroscopic control is a technique that
      allows surgeons to obtain satisfactory clinical results with good integration of
      the graft.

PMID- 30224230
TI  - Subcutaneous rupture of the flexor hallucis longus tendon at the musculotendinous
      junction in a soccer player.

PMID- 30224231
TI  - Shared co-expression networks in frontal cortex of the normal aged brain and
      schizophrenia.
AB  - Previous studies on the brain of people with schizophrenia have identified
      structural changes and gene expression changes, suggesting that brain aging maybe
      accelerated in people with schizophrenia. To better characterize gene expression
      profiles in schizophrenia and in the aged population we constructed co-expression
      networks using RNA-Seq data from frontal cortex. The first data set analysed was
      from 62 subjects with schizophrenia and 51 unaffected controls ranging in age
      from 19 to 63 years. The second separate data set was from normal control
      individuals ranging in age from 29 to 106 years. In the first data set, we found
      two co-expression modules significantly associated with schizophrenia. One was a
      downregulated co-expression module enriched for neuron function related genes and
      the other was an upregulated immune/inflammation-related module. In the second
      data set of normal individuals, we found seven co-expression modules
      significantly correlated with age. A comparison of the co-expression modules from
      the two data sets revealed a significant consensus in nodes associated with
      schizophrenia and those associated with normal aging. The results indicate that a
      co-expression module related to neuronal function is downregulated and an
      immune/inflammation related co-expression module is upregulated, and associated
      with cells of the blood vessels, in both schizophrenia and in normal aging. This
      finding adds further support to the hypothesis that there may be accelerated
      brain aging in schizophrenia.

PMID- 30224232
TI  - Process-Specific Alliances (PSAs) in Cognitive Neuroscience.
AB  - Most cognitive neuroscience theories have focused on the functions of individual
      brain regions, but cognitive abilities depend also on functional interactions
      among multiple regions. Many recent studies on these interactions have examined
      large-scale, resting-state networks, but these networks are difficult to link to
      theories about specific cognitive processes. Cognitive theories are easier to
      link to the mini-networks we call process specific alliances (PSAs). A PSA is a
      small team of brain regions that rapidly assemble to mediate a cognitive process
      in response to task demands but quickly disassemble when the process is no longer
      needed. We compare PSAs to resting-state networks and to other connectivity
      based, task-related networks, and we characterize the advantages and
      disadvantages of each type of network.

PMID- 30224233
TI  - Being a Beast Machine: The Somatic Basis of Selfhood.
AB  - Modern psychology has long focused on the body as the basis of the self.
      Recently, predictive processing accounts of interoception (perception of the body
      'from within') have become influential in accounting for experiences of body
      ownership and emotion. Here, we describe embodied selfhood in terms of
      'instrumental interoceptive inference' that emphasises allostatic regulation and
      physiological integrity. We apply this approach to the distinctive phenomenology
      of embodied selfhood, accounting for its non-object-like character and subjective
      stability over time. Our perspective has implications for the development of
      selfhood and illuminates longstanding debates about relations between life and
      mind, implying, contrary to Descartes, that experiences of embodied selfhood
      arise because of, and not in spite of, our nature as 'beast machines'.

PMID- 30224234
TI  - Interactive effect of serum uric acid and total bilirubin for micro-vascular
      disease of type 2 diabetes in China.
AB  - AIMS: Serum uric acid (SUA) and bilirubin at high levels had both pro-oxidant and
      anti-oxidant properties. The present study aimed to examine additive interactions
      between SUA and total bilirubin (TBIL) for the risk of micro-vascular disease
      (MVD) in type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional survey of
      6713 inpatients with T2DM was conducted in 81 tertiary care hospitals in China.
      MVD was defined as having either prior diabetic retinopathy (DR) or diabetic
      nephropathy (DN). Binary logistic regression was used to estimate odds ratios of
      SUA and TBIL for MVD. Additive interaction was measured by three indices, i.e.,
      relative excess risk due to interaction, attributable proportion due to
      interaction and synergy index. RESULTS: Among 6713 inpatients, 408 (6.08%)
      suffered from MVD. SUA >= 283 MUmol/l (i.e., its media) was defined as high SUA,
      and TBIL <11.5 MUmol/l (n = 2290 or 34.11%) was defined as low TBIL. Overall, 621
      patients were exposed to co-presence of high SUA and low TBIL. The co-presence of
      both factors greatly increased the effect sizes from 1.03(95%CI: 0.72-1.46) (high
      SUA alone) or 0.70(95%CI: 0.48-1.05) (low TBIL alone) to 1.90 (95%CI: 1.26-2.87)
      for MVD in multivariable analysis. The additive interaction of both factors was
      significant for MVD in both univariable analysis and multivariable analysis.
      CONCLUSIONS: Co-presence of both high SUA and low TBIL indentified a group of
      patients at a markedly increased risk of MVD in high-risk Chinese patients with
      T2DM.

PMID- 30224235
TI  - Ecology of the cardiovascular system: Part II - A focus on non-air related
      pollutants.
AB  - An integrated exposomic view of the relation between environment and
      cardiovascular health should consider the effects of both air and non-air related
      environmental stressors. Cardiovascular impacts of ambient air temperature,
      indoor and outdoor air pollution were recently reviewed. We aim, in this second
      part, to address the cardiovascular effects of noise, food pollutants, radiation,
      and some other emerging environmental factors. Road traffic noise exposure is
      associated with increased risk of premature arteriosclerosis, coronary artery
      disease, and stroke. Numerous studies report an increased prevalence of
      hypertension in people exposed to noise, especially while sleeping. Sleep
      disturbances generated by nocturnal noise are followed by a neuroendocrine stress
      response. Some oxidative and inflammatory endothelial reactions are observed
      during experimental session of noise exposure. Moreover, throughout the
      alimentation, the cardiovascular system is exposed to persistent organic
      pollutants (POPs) as dioxins or pesticides, and plastic associated chemicals
      (PACs), such as bisphenol A. Epidemiological studies show positive associations
      of exposures to POPs and PACs with diabetes, arteriosclerosis and cardiovascular
      disease incidence. POPs and PACS share some abilities to interact with nuclear
      receptors activating different pathways leading to oxidative stress, insulin
      resistance and angiotensin potentiation. Regarding radiation, survivors of
      nuclear explosion have an excess risk of cardiovascular disease. Dose-effect
      relationships remain debated, but an increased cardiovascular risk at low dose of
      radiation exposure may be of concern. Some emerging environmental factors like
      electromagnetic fields, greenspace and light exposure may also require further
      attention. Non-air related environmental stressors also play an important role in
      the burden of cardiovascular disease. Specific methodologies should be developed
      to assess the interactions between air and non-air related pollutants.

PMID- 30224236
TI  - Silent myocardial infarction and risk of heart failure: Current evidence and gaps
      in knowledge.
AB  - Coronary heart disease (CHD) is the most common underlying risk factor for heart
      failure (HF); up to one-third of the patients who are hospitalized for HF each
      year in the United States have a history of myocardial infarction (MI). Although
      silent MI (SMI) could account for up to one-half of all MIs, only a few studies
      examined the relationship between SMI and risk of HF. These few studies agreed on
      their conclusions that SMI is associated with increased risk of HF. However,
      there was less agreement on the magnitude of risk and the sex differences in the
      association between SMI and HF, which is probably due to the heterogeneity in how
      these studies defined SMI. This report summarizes and discusses the current
      evidence linking SMI to HF, the impact of the methods by which SMI is defined on
      the reported relationship between SMI and HF, the potential mechanisms for such
      relationship, the implications of these findings, and the gaps in knowledge that
      need to be addressed.

PMID- 30224237
TI  - Incidence and diagnoses of disorders of sex development in proximal hypospadias.
AB  - BACKGROUND: Evidence-based guidelines on evaluation of boys with proximal
      hypospadias for the possibility of a disorder of sex development (DSD) have yet
      to be developed. We aimed to investigate the incidence and diagnoses of DSD in
      patients with proximal hypospadias. METHODS: We retrospectively reviewed the
      records of consecutive boys who underwent proximal hypospadias repairs from 2006
      to Sept 2017. Data collected included scrotal anomaly, testes
      position/palpability, micropenis, DSD investigations, and surgical techniques.
      RESULTS: 165 patients were eligible for the study. 14 (8.5%) were diagnosed to
      have DSD. The diagnoses were 46,XX testicular DSD [n = 1], 46,XY DSD [n = 7;
      partial gonadal dysgenesis (PGD) = 3; 5alpha-reductase type 2 deficiency = 3;
      17alpha-hydroxylase deficiency = 1], Sex Chromosome DSD [n = 6; 45,X/46,XY PGD =
      4; Klinefelter = 2]. 3/7 (43%) patients with PGD had gonadal germ cell neoplasms.
      Of the DSD patients, 6/14 (43%), 11/14 (79%) and 11/14 (79%) had
      undescended/impalpable testes, micropenis and penoscrotal transposition/bifid
      scrotum, respectively, significantly higher prevalence rates than those without
      DSD diagnosis (p-values <0.05). 10/14 (71.4%) DSD patients underwent 2-stage
      repair compared with 57/151 (37.7%) of others without DSD diagnosis (p = 0.01).
      CONCLUSIONS: Patients presenting with proximal hypospadias and one or more of the
      coexisting anomalies of micropenis, undescended/impalpable testes, and
      penoscrotal transposition/bifid scrotum should warrant DSD evaluation. Presence
      of bilaterally descended testes in scrotum does not preclude the possibility of
      DSD. LEVEL OF EVIDENCE: IV.

PMID- 30224239
TI  - Shiga toxin-glycosphingolipid interaction: Status quo of research with focus on
      primary human brain and kidney endothelial cells.
AB  - Shiga toxin (Stx)-mediated injury of the kidneys and the brain represent the
      major extraintestinal complications in humans upon infection by enterohemorrhagic
      Escherichia coli (EHEC). Damage of renal and cerebral endothelial cells is the
      key event in the pathogenesis of the life-threatening hemolytic uremic syndrome
      (HUS). Stxs are AB5 toxins and the B-pentamers of the two clinically important
      Stx subtypes Stx1a and Stx2a preferentially bind to the glycosphingolipid
      globotriaosylceramide (Gb3Cer, Galalpha4Galbeta4Glcbeta1Cer) and to less extent
      to globotetraosylceramide (Gb4Cer, GalNAcbeta3Galalpha4Galbeta4Glcbeta1), which
      are expected to reside in lipid rafts in the plasma membrane of the human
      endothelium. This review summarizes the current knowledge on the Stx
      glycosphingolipid receptors and their lipid membrane ensemble in primary human
      brain microvascular endothelial cells (pHBMECs) and primary human renal
      glomerular endothelial cells (pHRGECs). Increasing knowledge on the precise
      initial molecular mechanisms by which Stxs interact with cellular targets will
      help to develop specific therapeutics and/or preventive measures to combat EHEC
      caused diseases.

PMID- 30224240
TI  - Dignity (yet) again. A rejoinder to de Miguel and Sanz.

PMID- 30224238
TI  - Infants with esophageal atresia and right aortic arch: Characteristics and
      outcomes from the Midwest Pediatric Surgery Consortium.
AB  - PURPOSE: Right sided aortic arch (RAA) is a rare anatomic finding in infants with
      esophageal atresia with or without tracheoesophageal fistula (EA/TEF). In the
      presence of RAA, significant controversy exists regarding optimal side for
      thoracotomy in repair of the EA/TEF. The purpose of this study was to
      characterize the incidence, demographics, surgical approach, and outcomes of
      patients with RAA and EA/TEF. METHODS: A multi-institutional, IRB approved,
      retrospective cohort study of infants with EA/TEF treated at 11 children's
      hospitals in the United States over a 5-year period (2009 to 2014) was performed.
      All patients had a minimum of one-year follow-up. RESULTS: In a cohort of 396
      infants with esophageal atresia, 20 (5%) had RAA, with 18 having EA with a distal
      TEF and 2 with pure EA. Compared to infants with left sided arch (LAA), RAA
      infants had a lower median birth weight, (1.96 kg (IQR 1.54-2.65) vs. 2.57 kg
      (2.00-3.03), p = 0.01), earlier gestational age (34.5 weeks (IQR 32-37) vs. 37
      weeks (35-39), p = 0.01), and a higher incidence of congenital heart disease (90%
      vs. 32%, p < 0.0001). The most common cardiac lesions in the RAA group were
      ventricular septal defect (7), tetralogy of Fallot (7) and vascular ring (5).
      Seventeen infants with RAA underwent successful EA repair, 12 (71%) via right
      thoracotomy and 5 (29%) through left thoracotomy. Anastomotic strictures trended
      toward a difference in RAA patients undergoing right thoracotomy for primary
      repair of their EA/TEF compared to left thoracotomy (50% vs. 0%, p = 0.1). Side
      of thoracotomy in RAA patients undergoing EA/TEF repair was not significantly
      associated with mortality, anastomotic leak, recurrent laryngeal nerve injury,
      recurrent fistula, or esophageal dehiscence (all p > 0.29). CONCLUSION: RAA in
      infants with EA/TEF is rare with an incidence of 5%. Compared to infants with
      EA/TEF and LAA, infants with EA/TEF and RAA are more severely ill with lower
      birth weight and higher rates of prematurity and complex congenital heart
      disease. In neonates with RAA, surgical repair of the EA/TEF is technically
      feasible via thoracotomy from either chest. A higher incidence of anastomotic
      strictures may occur with a right-sided approach. LEVEL OF EVIDENCE: Level III.

PMID- 30224241
TI  - Assisted reproductive technology in Beijing, 2013-2015.
AB  - RESEARCH QUESTION: Why are comprehensive and detailed reports of local or
      national utilization outcomes of assisted reproductive technology (ART) lacking
      in China? DESIGN: Retrospective collection of data on intrauterine insemination
      (IUI) and IVF and intracytoplasmic sperm injection (ICSI) in Beijing, including
      all 12 registered institutions with cycles, started between 1 January 2013 and 31
      December 2015. RESULTS: Clinical pregnancy rates (CPR) per aspiration and fresh
      embryo transfer were 39.1% and 43.2% in 2013, 40.1% and 45.4% in 2014, and 37.8%
      and 44.5% in 2015; live birth rates (LBR) per aspiration and per fresh embryo
      transfer were 31.7% and 35.0%, 32.3% and 36.6%, and 30.3% and 35.6%,
      respectively. In frozen embryo transfer (FET) cycles, the CPR per thawed transfer
      was 43.4%, 47.2% and 46.2%, respectively, resulting in LBR of 34.3%, 37.4% and
      36.5%. The prevalence of multiple pregnancies was 28.0-31.3% for fresh embryo
      transfer, and 23.5-25.9% for FET. The LBR was 8.8-9.1% after IUI with husband or
      partner's semen (IUI-H), and 16.7-19.7% after IUI with donor semen (IUI-D). The
      birth defect rate among live born infants was 1.52%, 0.42% and 0% after IUI-H,
      1.05%, 0.39% and 0.66% after IUI-D, 0.71%, 0.56% and 0.46% after fresh embryo
      transfer, and 0.73%, 0.20% and 0.18% after FET in 2013, 2014 and 2015,
      respectively. CONCLUSIONS: In Beijing over 3 years, the number of IVF-ICSI cycles
      has increased and the number of IUI cycles has decreased; IVF-ICSI outcomes are
      better and safer. Further effort should be made to lower the multiple pregnancy
      rates. A Chinese nationwide ART registry should be promoted.

PMID- 30224242
TI  - Profiles for long non-coding RNAs in ovarian granulosa cells from women with PCOS
      with or without hyperandrogenism.
AB  - RESEARCH QUESTION: What is the expression pattern of long non-coding RNAs
      (lncRNA) in ovarian granulosa cells of women with polycystic ovary syndrome
      (PCOS) with or without hyperandrogenism? DESIGN: Microarray screening of lncRNA
      was conducted in ovarian granulosa cells collected from women with PCOS with
      hyperandrogenism (PCOS-T) or without hyperandrogenism (PCOS-N) and control
      participants, with four samples in each group. This was followed by hierarchy
      clustering, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway
      analyses. Several candidate lncRNA were randomly selected for quantitative
      polymerase chain reaction validation in another 54 patients. To predict the
      regulatory effect of lncRNA on hyperandrogenism, a co-expression network was
      plotted using differentially hexpressed lncRNA with statistical significance (>=
      twofold; P < 0.05) in PCOS-T compared with PCOS-N. RESULTS: A total of 3000 and
      1030 differentially expressed lncRNA (>= twofold change) were detected in PCOS-T
      compared with control and PCOS-N, respectively. A total of 1361 differentially
      expressed lncRNA were detected in PCOS-N compared with controls. Corticotropin
      releasing hormone binding protein is consistently the up-regulated lncRNA with
      the highest fold-change in PCOS-T compared with either control or PCOS-N. Gene
      ontology and pathway analysis showed that dysregulated lncRNA in PCOS-T have a
      regulatory role in mitochondrial function by interacting with transcription
      factors such as YY1 and SIX5. CONCLUSIONS: The expression patterns of lncRNA in
      women with PCOS were ascertained by microarray. Many lncRNA were differentially
      expressed in PCOS-T compared with PCOS-N, suggesting that they may play a key
      role in steroid genesis and metabolism.

PMID- 30224243
TI  - Social egg freezing: Who chooses and who uses?

PMID- 30224244
TI  - Effect of formalin fixation on pcr amplification of DNA isolated from healthy
      autopsy tissues.
AB  - The aim of this study is to investigate the effects of formalin fixation on the
      degradation of DNA molecules in five different healthy tissues exempted during
      the autopsy, as well as the selection of the method that is most suitable for the
      DNA isolation. Heart muscle, liver, brain, lung and kidney tissue obtained from
      the healthy people who suddenly died from a violent death were used. The parts of
      tissue were fixed in 10% phosphate-buffered formalin as well as in 4% unbuffered
      formalin at room temperature. Morphology of tissue was studied using H&E
      staining. The DNA was isolated 6 h, 1-7 days (every 24 h), 10, 14, 28 days and 2
      months after fixation using two different methods: extraction with phenol
      chloroform-isoamyl alcohol as well as with PureLink Genomic DNA Kit. Yield and
      purity of the DNA samples were measured spectrophotometrically at 260 nm and 280
      nm. The PCR amplifications of the glycerol-3-phosphate dehydrogenase 1 (GPD1, 150
      bp), beta actin (ACTB, 262 bp) and ribosomal protein L4 (RPL4, 407 bp) genes were
      performed to evaluate the degree of DNA fragmentation. The RPL4 gene was
      amplified up to 72 h, ACTB gene up to 14 days and GPD1 gene up to 28 days from
      tissue fixed in phosphate-buffered formalin using phenol-chloroform
      isoamylalcohol protocol for DNA isolation. Liver and kidney gave better results
      of PCR amplification, but statistical significance between tissues was not found.
      Preserving period, fixative and DNA extracting method are important factors for
      successful PCR amplification. The healthy tissue, fixed in phosphate-formalin up
      to 28 days, can be useful source in molecular studies. Tissues fixed in
      unbuffered formalin are suitable for molecular analysis up to 7 days.

PMID- 30224245
TI  - Cholecalciferol in ethanol-preferring rats muscle fibers increases the number and
      area of type II fibers.
AB  - The chronic use of ethanol causes neuropathy and atrophy of type II fibers and
      promotes vitamin D decrease. This study evaluated cholecalciferol effects on the
      deep fibular nerve and extensor digitorum longus (EDL) muscle using an UChB
      ethanol-preferring rats model. Blood analyses were carried out to measure levels
      of 25-hydroxycholecalciferol (25(OH)D), calcium (Ca2+), Phosphorus (P), and
      parathyroid hormone (PTH). It was used EDL muscle to evaluate oxidative stress.
      The deep fibular nerve and EDL muscle were used for morphologic and morphometric
      assessment. 25(OH)D plasma levels were higher in the supplemented group and no
      alterations were observed in other parameters including the oxidative stress
      evaluation. The G ratio remained constant which indicates nervous conduction
      normality. Cholecalciferol supplementation promoted an increase in the number and
      area of type II fibers and a decrease in the area of type I fibers. In the
      studied model, there was neither alcoholic myopathy nor neuropathy. The EDL
      muscle glycolytic patterns in the high-drinker UChB rats may be associated with
      the differential effects of cholecalciferol on metabolism and protein synthesis
      in skeletal muscle.

PMID- 30224246
TI  - A simple and efficient toolset for analysing mitochondrial trafficking in
      neuronal cells.
AB  - Mitochondria are crucial for cells, supplying up to 90% of the energy
      requirements for neurons. Their correct localisation is crucial and ensured by a
      transport system. Mitochondrial trafficking in neurons is particularly critical,
      because mitochondria must leave the soma and travel along the axon and dendritic
      network to facilitate neuronal function. Abnormal mitochondrial trafficking has
      been reported in several neurological disorders, therefore the ability to
      quantify and analyse mitochondrial trafficking is vital to improving our
      understanding of their pathogenesis. Commercial software currently lacks an
      automated approach for performing such quantitation. Here we demonstrate the
      development of the Mitochondrial Trafficking and Distribution (MiTrakD) analysis
      toolset, which consists of simple and free-to-use instructions for mitochondrial
      trafficking analysis using time-lapse microscopy. MiTrakD utilises existing Fiji
      (ImageJ) tools for semi-automated, fast and efficient analysis of mitochondrial
      trafficking and distribution, including velocity, abundance, localisation and
      distance travelled in neurons. We document MiTrakD's efficiency and accuracy by
      analysing mitochondrial trafficking using two-dimensional fluorescence images of
      cortical neurons of wild type mice after 6 days (DIV6), 10 days (DIV10) and 14
      days (DIV14) of in vitro incubation. Using MiTrakD we have demonstrated that
      neurons at all developmental stages exhibited the same percentage of mobile
      mitochondria, all of which travel in equidistance. Interestingly, the
      mitochondria in neurons at DIV10 were in greater abundance and were faster than
      those at DIV6 and DIV14. We can also conclude that MiTrakD is more efficient than
      manual analysis and is an accurate and reliable tool for performing mitochondrial
      trafficking analysis in neuronal cells.

PMID- 30224247
TI  - Colorectal peritoneal carcinomatosis: What is the future of HIPEC?

PMID- 30224248
TI  - Surgery in perforated pediatric intestinal lymphoma.
AB  - BACKGROUND: Perforation is the most common surgical complication in pediatric
      intestinal lymphoma. During operation, many surgical decisions are debatable.
      AIM: To assess the outcome of surgical management of perforated pediatric
      intestinal lymphoma. PATIENTS AND METHODS: This is a retrospective analysis of
      all pediatric patients (<18 years old) with intestinal lymphoma treated in our
      hospital between July 2007 and June 2017. Risk factors for perforation, type of
      management and outcome in cases of intestinal perforation were analyzed. RESULTS:
      The study included 240 patients with intestinal lymphoma. Perforation developed
      in 16 patients (6.7%) with a median age of 5.3 (range: 2.8-15.7) years. Most of
      the patients (92.5%) had Burkitt lymphoma. The ileum was the most common site of
      perforation (n = 10). Perforation occurred at presentation (n = 2), during
      induction (n = 10), during maintenance chemotherapy (n = 2), or at relapse (n =
      2). Primary resection anastomosis was done in 12 patients. The resected specimen
      showed a viable tumor in ten patients. Wound infection (25%) and dehiscence
      (12.5%) were the most common postoperative complications. The 5-year overall and
      event-free survivals of patients with perforation were 78.6% and 71.4%,
      respectively, compared with 85.5% and 81.2% in non-perforated patients; the
      difference was not significant (p = 0.374 and p = 0.270, respectively).
      CONCLUSION: Perforation is not an adverse prognostic factor for survival in
      pediatric intestinal lymphoma patients. Primary resection anastomosis seems to be
      a safe option if complete tumor resection is feasible.

PMID- 30224249
TI  - Reply to: Selective history of radioactive iodine in medicine: Inexactitudes no
      longer.

PMID- 30224250
TI  - Venoarterial Extracorporeal Membrane Oxygenation and Ventricular Assistance With
      Impella CP in an Amniotic Fluid Embolism.

PMID- 30224251
TI  - Role of CMR in Prognostic Stratification in Myocardial Infarction.

PMID- 30224252
TI  - Comment on "Mitochondrial oxidative stress, endothelial function and metabolic
      control in patients with type II diabetes and periodontitis: A randomized
      controlled clinical trial".

PMID- 30224253
TI  - Pulmonary vasodilator therapies are of no benefit in pulmonary hypertension due
      to left heart disease: A meta-analysis.
AB  - BACKGROUND: Pulmonary hypertension complicating left heart disease (PH-LHD) is
      the most common cause of PH. Off-label use of pulmonary arterial hypertension
      (PAH) medications for PH-LHD is prevalent, despite a lack of clinical data
      supporting their use. METHODS: A systematic review and meta-analysis was
      performed. Comprehensive search of all available literature to date identified
      ten randomised, placebo controlled trials comprising 439 treated
      (Phosphodiesterase 5 inhibitors: n = 206; guanylate cyclase stimulators: n = 132;
      endothelin receptor antagonists: n = 101) and 338 placebo patients. Random
      effects model was employed to assess outcomes in the treatment compared to the
      placebo control arm. RESULTS: The risks of all-cause mortality, cardiovascular
      mortality and worsening heart failure were numerically higher in the treated
      compared to the control group, although not statistically (all-cause mortality:
      RR = 1.97, 95% CI: 0.64-6.05, p = 0.24; cardiovascular mortality: RR = 2.01, 95%
      CI: 0.39-10.34, p = 0.4; worsening heart failure: RR = 1.23, 95% CI: 0.68-2.25, p
      = 0.49). Conversely, right heart hemodynamics improved numerically in the treated
      group, also without being significant (mean pulmonary artery pressure: MWD = 
      5.13 mm Hg, 95% CI: -13.2-2.9, p = 0.21; pulmonary vascular resistance: MWD = 
      0.87 WU, 95% CI: -1.75-0.1, p = 0.053). CONCLUSIONS: The current meta-analysis
      demonstrated that there is no current evidence to support the widespread use of
      PAH therapy in PH-LHD. On the basis of a numerically increased risk of clinical
      harm, these agents should not be prescribed in this setting, unless further
      evidence of benefit arises in the future.

PMID- 30224254
TI  - Early discharge and late onset conduction disturbances - A conflict of interest?

PMID- 30224255
TI  - Some thoughts about the predictive role of heart rate in takotsubo syndrome.

PMID- 30224256
TI  - Metal-on-metal hips and heart failure - Can we relax?

PMID- 30224257
TI  - Comparison of prescription rates and clinical outcomes in acute coronary syndrome
      patients who underwent percutaneous coronary intervention using different P2Y12
      inhibitors in a large observational study.
AB  - BACKGROUND: To compare the prescription rates, safety, and efficacy of
      contemporary P2Y12 inhibitors in acute coronary syndrome (ACS) patients following
      percutaneous coronary intervention (PCI). METHODS: From 9684 ACS patients who
      underwent PCI in a nationwide, real-world registry, we compared prescription
      rates, bleeding, and major adverse cardiac events (MACEs: cardiac death, nonfatal
      myocardial infarction, or stroke) according to ticagrelor, prasugrel, or
      clopidogrel use. RESULTS: The prescription rates of ticagrelor, prasugrel, and
      clopidogrel were 15.2%, 11.7%, and 73.0%, respectively. In-hospital bleeding
      occurred in 565 (5.8%) patients, with 108 (7.3%), 80 (7.9%), and 377 (5.3%)
      patients using ticagrelor, prasugrel, and clopidogrel, respectively, with
      significantly higher incidence in ticagrelor (p = 0.008) and prasugrel (p =
      0.026) users than in clopidogrel users. Ticagrelor and prasugrel were not
      different in terms of in-hospital bleeding (p = 0.159). MACEs occurred in 804
      patients (8.3%), with 82 (5.6%), 69 (6.1%), and 653 (9.2%) patients in
      ticagrelor, prasugrel, and clopidogrel, respectively (median follow-up, 468
      days). Ticagrelor (p = 0.001) and prasugrel (p = 0.001) were associated with
      fewer MACEs than clopidogrel; the difference between ticagrelor and prasugrel for
      fewer MACEs was nonsignificant (p = 0.235). CONCLUSIONS: In real-world ACS
      patients following PCI, ticagrelor and prasugrel were not prescribed at higher
      rates than clopidogrel, but were found to improve clinical outcomes, albeit they
      induced bleeding more frequently. No differences were observed in bleeding and
      outcomes in ticagrelor versus prasugrel.

PMID- 30224259
TI  - The wireless revolution and cardiorespiratory system monitoring.

PMID- 30224258
TI  - Depression and anxiety are associated with high health care utilization and
      mortality among adults with congenital heart disease.
AB  - BACKGROUND: The significance of depression/anxiety among ACHD patients in terms
      of health care utilization is unknown and data on the association with mortality
      are scarce. METHODS: Analyses comprised 8334 ACHD patients, age >= 18 years,
      insured by a large healthcare organization (2007-2011). Depression/anxiety were
      determined by diagnoses and treatments recorded in the organization database.
      Adjusted utilization relative rates (RRs) were estimated with negative binomial
      models and mortality hazard ratios (HRs) with the Cox proportional hazard model.
      RESULTS: ACHD patients with depression/anxiety (N = 2950, 35%) were more likely
      to be older (mean +/- SD: 54 +/- 17 vs. 45 +/- 18 years), women (61% vs. 45%),
      and have comorbidities than counterparts without depression/anxiety. Following
      multivariable adjustment, patients with depression/anxiety had more primary care
      and cardiology clinic visits, more emergency department visits and more
      hospitalizations. RRs (95% confidence interval) were: 1.31 (1.27-1.35); 1.07
      (1.01-1.13); 1.60 (1.46-1.77); and 1.18 (1.08-1.29) respectively, for diagnosis
      before the study period, and 1.36 (1.31-1.42); 1.22 (1.14-1.30); 1.43 (1.24-1.60)
      and 1.47 (1.33-1.64), respectively, for diagnosis during the study. Stratifying
      by age, the highest adjusted primary care and cardiology visit RRs were found
      among 18-24 years old patients and the lowest among patients >=65 years. Between
      2007 and 2017, 905 patients died. Depression/anxiety were associated with
      increased mortality risk with adjusted HRs: 1.10 (95% CI: 0.94-1.29) for past
      diagnosis and 1.40 (1.17-1.67) for study period depression/anxiety diagnosis.
      CONCLUSIONS: Depression/anxiety in ACHD patients is associated with increased
      health-care utilization and a higher risk of death. The efficacy of addressing
      patients' psychosocial needs in optimizing health-care utilization and improving
      prognosis needs further evaluation.

PMID- 30224260
TI  - Admission heart rate in the Takotsubo syndrome - An early marker of the severity
      of cardiac dysfunction and the risk of in-hospital complications.

PMID- 30224261
TI  - Effectiveness of CHA2DS2-VASc based decision support on stroke prevention in
      atrial fibrillation: A cluster randomised trial in general practice.
AB  - BACKGROUND: Guidelines on atrial fibrillation (AF) recommend the CHA2DS2-VASc
      rule for anticoagulant decision-making, but underuse exists. We studied the
      impact of an automated decision support on stroke prevention in patients with AF
      in a cluster randomised trial in general practice. METHODS: Intervention
      practices were provided with a CHA2DS2-VASc based anticoagulant treatment
      recommendation. Reference practices provided care as usual. The primary outcome
      was incidence of ischaemic stroke, transient ischaemic attack (TIA) and/or
      thromboembolism (TE). Secondary outcomes were bleeding and the proportion of
      patients on guideline recommended anticoagulant treatment. RESULTS: In total,
      1129 AF patients were included in the 19 intervention practices and 1226 AF
      patients in the 19 reference practices. The median age was 77 (interquartile
      range (IQR) 68-75) years, the median CHA2DS2-VASc score was 3.0 (IQR 2.0-5.0).
      Underuse of anticoagulants in patients with CHA2DS2-VASc score >= 2 was 6.6%.
      After a median follow-up of 2.7 years (IQR 2.3-3.0), the incidence rate per 100
      person-years of ischaemic stroke/TIA/TE was 1.96 in the intervention group and
      1.42 in the reference group (hazard ratio (HR) 1.3, 95% C.I. 0.8-2.1). No
      difference was observed in the rate of bleeding (0.79 versus 0.82), or in the
      underuse (7.2% versus 8.2%) or overuse (8.0% versus 7.9%) of anticoagulation.
      CONCLUSIONS: In this study in patients with AF in general practice, underuse of
      anticoagulants was relatively low. Providing practitioners with CHA2DS2-VASc
      based decision support did not result in a reduction in stroke incidence, affect
      bleeding risk or anticoagulant over- or underuse.

PMID- 30224262
TI  - UV-B strengthens antioxidant responses to drought in Nicotiana benthamiana leaves
      not only as supplementary irradiation but also as pre-treatment.
AB  - Potentials of UV-B (280-315 nm) radiation to alleviate effects of water deficit
      were studied using Nicotiana benthamiana plants in growth chambers. 10-days of
      limited watering resulted in 40% loss of soil water content as compared to well
      watered controls. This drought was applied in three different ways: (i) in
      itself, (ii) after 4-days exposure of 6.9 kJ m-2 d-1 biologically effective
      supplementary UV-B radiation as pre-treatment, or (iii) in parallel with 6.9 kJ m
      2 d-1 biologically effective supplementary UV-B. Responses were examined in two
      leaf groups: fully developed mature leaves (ML) and young leaves emerging during
      the 10-day treatment (YL). ML responded to UV-B or drought as single factor
      treatments with 7-14% loss of photochemical yield, while YL photochemistry was
      not decreased under the same conditions. The parallel two-factor treatment had no
      aggravating effect but alleviated drought-induced loss of leaf photochemistry in
      ML. Several positive single factor effects of drought or UV-B on antioxidants
      remained significant in the two-factor treatment both in ML and YL. Effects of
      the two factors applied in parallel were additive (equal to the sum of the
      effects caused by single factors separately) on total antioxidant capacities and
      singlet oxygen neutralizing; and synergistic (larger than the sum of single
      factor effects) on the flavonoid index in ML. A sequential application of UV-B
      and drought had additive positive effects on antioxidant capacity and flavonoid
      index of ML suggesting lasting effects of UV-B pre-treatment.

PMID- 30224263
TI  - Cross-cultural adaptation of the Amsterdam inventory for auditory disability and
      handicap to Brazilian Portuguese.
AB  - INTRODUCTION: Patient-reported outcome measures, inventory and or questionnaire,
      allow patients to present their perspective of the impact of their individual
      condition on a day-to-day basis, independent of the analysis of test results by
      the expert clinician. Outcome measures are recommended when there is evidence
      showing their reliability, validity and sensitivity. There are standardized
      patient-reported outcome measures for hearing in English language; however, other
      languages lack these instruments. OBJECTIVE: Adapt the Amsterdam inventory for
      auditory disability and handicap to Brazilian Portuguese and analyze its
      validation measures. METHODS: We conducted two studies. In Study 1, we translated
      and adapted the Amsterdam inventory for auditory disability and handicap to
      Brazilian Portuguese according to good practice guidelines; this included the pre
      test stage. In Study 2, we administered the Portuguese version to adults with and
      without hearing loss (n=31 and 18, respectively) and analyzed the measures of
      instrument validation, reliability, and reproducibility. Moreover, we calculated
      the correlation between pure tone thresholds and scores on the questionnaire.
      RESULTS: The results obtained in Study 1 demonstrated the feasibility of the
      translation process and the instrument's cultural adaptation, as well as its
      applicability, resulting in the Portuguese version of the Amsterdam inventory for
      auditory disability and handicap. In Study 2, the results revealed construct
      values for the questions and domains, as well as for the total reliable score.
      The intra-interviewer test-retest condition showed excellent reproducibility
      (ICC=0.97). Finally, there was a strong positive correlation (r=0.83) between the
      mean pure tone threshold and the hearing difficulties values, as measured by the
      instrument's scores. CONCLUSION: The English version of the Amsterdam inventory
      for auditory disability and handicap could be translated and adapted to Brazilian
      Portuguese. An analyses of the validation process yielded reliable, consistent,
      and stable results.

PMID- 30224264
TI  - Current Diagnostic Criteria for Testosterone Deficiency Are Inadequate.
AB  - Current methods for diagnosing testosterone deficiency are inadequate. It is time
      to rethink how we determine who is a candidate for treatment, with a goal of
      helping our patients. Free testosterone appears more accurate than total
      testosterone.

PMID- 30224265
TI  - The impact of orthokeratology lens wear on binocular vision and accommodation: A
      short-term prospective study.
AB  - PURPOSE: To investigate the effects of short-term orthokeratology (OK) on
      accommodation and binocular visual function in young adults. METHODS: Twenty-four
      myopes (18 to 38 years) were fitted with OK lenses in both eyes. Best corrected
      distance visual acuity (VA), subjective and objective refractions, corneal
      topography and a series of binocular vision tests were measured at baseline (BL)
      before lens wear and then repeated after 28 nights of OK. Data from 15 subjects
      who demonstrated successful OK lens fit are reported. RESULTS: Corneal flattening
      and hyperopic shifts in spherical equivalent refractive error (all p < 0.001)
      after 28 nights of OK indicated myopic correction. Improvement in best corrected
      distance VA was measured after OK (right eye p = 0.021; left eye p = 0.014).
      Although there was no significant change in mean distance and near phorias and
      stereoacuity scores after OK compared to BL, there was a significant reduction in
      standard deviation (SD) and range of data (distance p = 0.01; near p = 0.02;
      stereoacuity p < 0.001). While there appeared to be an improvement in distance
      accommodative facility after OK, this failed to reach statistical significance (p
      = 0.053). Furthermore, there was no change in AC/A gradients with +/-1 D and +/-2
      D lenses after OK compared to BL. CONCLUSIONS: Binocular vision remained
      unchanged after OK, although variability of phoria and stereoacuity measures
      reduced. This suggests that OK improves or maintains accommodative and binocular
      vision function in young adult myopes who achieve good vision with OK. Myopes
      with phorias outside normal ranges and/or poor distance accommodative facility
      may benefit most with OK, in binocular and accommodative function.

PMID- 30224266
TI  - The importance of preclinical diagnostics in Parkinson disease.
AB  - Given the increasing recognition that neurodegeneration begins decades before the
      appearance of motor symptoms of Parkinson disease (PD), recent attention has
      turned to methods of preclinical or prodromal diagnosis. Accurate preclinical
      diagnosis of individuals at high risk of developing manifest motor PD can improve
      clinical counseling as well as provide an enriched cohort for studies of possible
      disease-modifying therapies. In this review article, the authors synthesize the
      myriad clinical, radiographic, and biochemical signatures of preclinical PD, with
      an emphasis on biomarkers that may provide accurate population screening for the
      disease. As individual biomarkers have relatively lowsensitivity and specificity,
      any population-based approach to preclinical diagnosis will likely combine
      multiple biomarkers to improve both negative and positive predictive value.

PMID- 30224267
TI  - Dyspnea: An underestimated symptom in Parkinson's disease.
AB  - INTRODUCTION: Dyspnea is one of the least well-characterized non-motor symptoms
      (NMS) associated with Parkinson's disease (PD). OBJECTIVE: To determine the
      frequency of dyspnea in a large, single-center cohort of consecutive PD patients
      with no history of lung or heart disease, and to compare clinical features in
      dyspneic vs. non-dyspneic patients. METHODS: Patients with abnormal
      cardiovascular and pulmonary results in a clinical examination were excluded. A
      positive response to at least one question ("In the last month, have you suffered
      from breathlessness?" and "In the last month, have you had trouble breathing
      normally?") was considered to signify the experience of dyspnea. MDS-UPDRS,
      global cognitive performance, non-motor symptoms and quality of life were
      assessed. RESULTS: In the cohort of 153 non-demented PD patients (mean age +/-
      standard deviation: 63.9 +/- 7.4; mean disease duration: 9.2 +/- 6.1 years), the
      mean [95% confidence interval (CI)] frequency of dyspnea was 39.2% (31.5-47).
      After adjustment for disease severity, PD patients with dyspnea had a
      significantly higher Movement Disorders Society Unified Parkinson's Disease
      Rating Scale part I, II and IV scores, a higher HAD anxiety and depression scores
      and a significantly higher 8-item Parkinson's Disease Questionnaire. CONCLUSION:
      Dyspnea is a frequent NMS in PD. Its pathophysiology and prognostic value need
      more investigation.

PMID- 30224268
TI  - [ENT benign lesions and pseudo-tumors: Case No. 6].

PMID- 30224270
TI  - A proposal for prospective evaluation of elderly subjects with low Glasgow Coma
      Scale.

PMID- 30224269
TI  - Community-Based Outreach and Treatment for Underserved Older Adults With
      Clinically Significant Worry: A Randomized Controlled Trial.
AB  - OBJECTIVE: To determine whether Calmer Life (CL) improved worry, generalized
      anxiety disorder-related (GAD-related) symptoms, anxiety, depression, sleep,
      trauma-related symptoms, functional status, and quality of life better than
      Enhanced Community Care with Resource Counseling (ECC-RC) at 6 months and 9
      months. METHODS: A randomized, controlled, comparative-effectiveness study
      involving underserved, low-income, mostly minority neighborhoods in Houston,
      Texas, looked at individuals >=50 with significant worry and interest in
      psychosocial treatment. Interventions were CL, cognitive behavioral therapy with
      resource counseling, facilitation of communication with primary care providers
      about worry/anxiety, integration of religion/spirituality, person-centered skill
      content and delivery and nontraditional community providers, ECC-RC, and enhanced
      standard community-based information/ resource counseling addressing basic unmet
      and mental health needs. Primary outcomes were worry and GAD-related symptom
      severity. Secondary outcomes were anxiety, depression, sleep difficulties, trauma
      related symptoms, functional status, quality of life, service use and
      satisfaction. RESULTS: Similar, moderate improvements followed CL and ECC-RC on
      worry, GAD-related symptoms, anxiety, depression, sleep, trauma-related symptoms,
      and mental health quality of life at 6 and 9 months, but with symptoms at both
      times and higher satisfaction with CL at both. Fewer ECC-RC participants reported
      a hospital admission in the prior 3 months than those in CL at 6 and 9 months; at
      9 months, fewer reported a visit with a provider in the previous 3 months.
      CONCLUSION: Both interventions showed similar improvements at 6 and 9 months, but
      symptoms remained that might require care. Either intervention or a combination
      may be useful for low-income older adults with identified worry/anxiety.

PMID- 30224271
TI  - Silicone pneumonitis, diffuse alveolar hemorrhage and acute respiratory distress
      syndrome from gluteal silicone injections.
AB  - Fatal complications from illegal cosmetic injection of nonmedical-grade liquid
      silicone (polydimethylsiloxane) by unlicensed providers are becoming more common.
      Silicone embolization syndrome (SES) can rapidly progress to pneumonitis and
      diffuse alveolar hemorrhage. Prompt and aggressive management with high-dose
      steroids and lung-protective ventilation strategies to minimize acute respiratory
      distress syndrome (ARDS) can be lifesaving. We present the case of a patient
      presenting with abdominal pain and shortness of breath who quickly developed
      respiratory failure. The patient recently had received bilateral gluteal silicone
      injections from an unlicensed provider.

PMID- 30224272
TI  - Multimodal analgesia in crotalid snakebite envenomation: A novel use of femoral
      nerve block.
AB  - Snakebite envenomations occur throughout the United States, with most
      envenomations resulting from Crotalid bites. These envenomations can result in
      severe pain despite aggressive analgesia due to effects of venom toxins. We
      report a case in which we treated a 44- year-old man who sustained a Copperhead
      (Agkistrodon contortrix) bite to his left hallux with progressive local toxicity,
      including severe pain radiating into his upper leg, without evidence of
      compartment syndrome or coagulopathy. His pain was unresponsive to multiple doses
      of opioids. We performed a fascia iliaca compartment femoral nerve block under
      dynamic ultrasound guidance with 20 mL of 0.25% bupivacaine, which provided
      substantial pain relief in his upper leg. To our knowledge, this is a novel
      application of regional anesthesia with peripheral nerve block. We demonstrate
      fascia iliaca compartment femoral nerve block may be a safe, beneficial technique
      for emergency physicians to utilize in providing multimodal analgesia in Crotalid
      envenomation.

PMID- 30224274
TI  - Evaluation of a shared decision making educational program: The Ottawa Decision
      Support Tutorial.
AB  - OBJECTIVE: To evaluate the Ottawa Decision Support Tutorial (ODST), an open
      access shared decision making educational program. METHODS: We conducted a post
      test study. Eligible participants completed a knowledge test and/or acceptability
      survey after completing ODST version 1 (2007-2013), version 2 (2013-2015), or
      version 3 (2015-2017). We conducted descriptive analysis and compared outcomes
      across versions using log transformed linear regression (knowledge) and log
      binomial regression (acceptability). Content analysis explored verbatim
      suggestions to improve the ODST. RESULTS: Overall, 6604 users completed the
      knowledge test and 4276 completed the acceptability survey. The median knowledge
      test score was 8/10 (IQR = 7-9) with 68% of users achieving a passing grade of
      7.5/10. Users who completed version 2 had the highest median knowledge scores
      (version 1 = 7.9, version 2 = 8.5, version 3 = 8.0, p < 0.001) and pass rate
      (version 1 = 63%, version 2 = 73%, version 3 = 69%). Acceptability was high, with
      90% reporting a good or excellent overall impression. Few users suggested
      improvements (readability, presentation, audiovisual). CONCLUSIONS: Most users
      passed the ODST knowledge test and rated the tutorial as acceptable. We will use
      feedback to improve the ODST. PRACTICE IMPLICATIONS: The ODST is an inexpensive
      and widely accessible intervention that can be used to educate healthcare
      providers about SDM and decision support.

PMID- 30224273
TI  - Survival by Histologic Subtype of Malignant Pleural Mesothelioma and the Impact
      of Surgical Resection on Overall Survival.
AB  - INTRODUCTION: For the 3 histologic subtypes of malignant pleural mesothelioma
      (MPM)-epithelioid, sarcomatoid, and biphasic-the magnitude of benefit with
      surgical management remains underdefined. MATERIALS AND METHODS: The National
      Cancer Data Base was queried for newly diagnosed nonmetastatic MPM with known
      histology. Patients in each histologic group were dichotomized into those
      receiving gross macroscopic resection versus lack thereof/no surgery. Kaplan
      Meier analysis evaluated overall survival (OS) between cohorts; multivariable Cox
      proportional hazards modeling assessed factors associated with OS. After
      propensity matching, survival was evaluated for each histologic subtype with and
      without surgery. RESULTS: Overall, 4207 patients (68% epithelioid, 18%
      sarcomatoid, 13% biphasic) met the study criteria. Before propensity matching,
      patients with epithelioid disease experienced the highest median OS (14.4
      months), followed by biphasic (9.5 months) and sarcomatoid (5.3 months) disease;
      this also persisted after propensity matching (P < .001). After propensity
      matching, surgery was associated with significantly improved OS for epithelioid
      (20.9 vs. 14.7 months, P < .001) and biphasic (14.5 vs. 8.8 months, P = .013) but
      not sarcomatoid (11.2 vs. 6.5 months, P = .140) disease. On multivariable
      analysis, factors predictive of poorer OS included advanced age, male gender,
      uninsured status, urban residence, treatment at community centers, and T4/N2
      disease (all P < .05). Chemotherapy and surgery were independently associated
      with improved OS, as was histology (all P < .001). CONCLUSION: This large
      investigation evaluated surgical practice patterns and survival by histology for
      MPM and found that histology independently affects survival. Gross macroscopic
      resection is associated with significantly increased survival in epithelioid and
      biphasic, but not sarcomatoid, disease. However, the decision to perform surgery
      should continue to be individualized in light of available randomized data.

PMID- 30224275
TI  - Does silence speak louder than words? The impact of oncologists' emotion-oriented
      communication on analogue patients' information recall and emotional stress.
AB  - OBJECTIVE: The impact of two types of oncologists' emotion-oriented communication
      on participants' recall of medical information was investigated, and the
      potential mediation by a reduction in emotional stress. Additionally, moderation
      effects by personal characteristics were explored. METHODS: An oncologist's
      communication in response to a patient's emotional expressions was manipulated
      during a videotaped, scripted bad-news consultation. Three conditions were
      created: 1) standard communication, 2) emotion-oriented silence, and 3) emotion
      oriented speech. Participants (N = 217) were randomly allocated to one of the
      three conditions. Measurements included information recall (free recall and
      recognition), emotional stress (self-reported and physiological), and personal
      characteristics. RESULTS: Emotion-oriented silence (p = .002) and speech (p =
      .019) enhanced information recognition compared to standard communication. No
      differences in free recall were found. Emotional stress did not mediate these
      relations. Poorer functional health literacy predicted poorer recognition, but
      this was counteracted by emotion-oriented communication. CONCLUSIONS: By means of
      acknowledging, exploring, empathic and supportive statements, and attentive
      silence, the oncologist's communication resulted in better information
      recognition. How oncologists' communication impacts patients' information recall
      warrants further investigation, as this could not be explained by reducing
      emotional stress. PRACTICE IMPLICATIONS: These insights will help educators to
      validate the relevance of emotion-oriented strategies, and encourage oncologists
      to adopt them.

PMID- 30224276
TI  - Editorial on Advancing midwifery education.

PMID- 30224277
TI  - High-throughput gas chromatography-mass spectrometry analysis of pesticide
      residues in spices by using the enhanced matrix removal-lipid and the sample
      dilution approach.
AB  - Spices are known as difficult matrices that contain variable amounts of fats,
      piperine or many other matrix constituents. The increasing sensitivity of new GC
      MS/MS platforms opens new approaches to analyze pesticide residue in complex
      matrices such as spices, by sample dilution. The aim of this work is to develop
      and validate an effective multiresidue method for the analysis of pesticide
      residues in spices by GC-MS/MS. In this paper, we highlight the importance of
      reducing matrix interferences generated from co-extractive components of spices.
      Moreover, we emphasize the concern of obtaining clean extracts requiring less
      instrument maintenance. By evaluating the total ion chromatograms (TIC) on GC
      Orbitrap-MS of different extracts using various sorbents, QuEChERS citrate using
      EMR-Lipid sorbent resulted in the cleanest extract among Z-Sep, Primary secondary
      amine (PSA), Oasis(r) Prime HLB, and SupelcleanTM Ultra cartridges that consist
      of a top bed of PSA, C18 and GrashsphereTM 2031 and a bottom bed of Z-Sep. Later,
      the analyses were performed on a GC-QQQ-MS/MS, applying a 15 min runtime method
      covering 205 compounds. The samples were diluted 25 times before the injection
      bearing in mind that the instrumental LOQs reached (iLOQ) were 2 ng g-1 and the
      method LOQs (mLOQ) were 50 ng g-1. Good recoveries between 70 and 120% with RSDs
      lower than 20% were observed for 90% of the compounds in black pepper and for 83%
      of the compounds in cayenne pepper. To demonstrate the applicability of the
      proposed method, 50 real dried and non-dried spice samples were analyzed. The
      most detected pesticides were metalaxyl, chlorpyrifos, tebuconazole, ethion, and
      chinomethionate.

PMID- 30224278
TI  - Coupling a gamma-ray detector with asymmetrical flow field flow fractionation
      (AF4): Application to a drug-delivery system for alpha-therapy.
AB  - Alpha-particle-emitting radionuclides have been the subject of considerable
      investigation as cancer therapeutics, since they have the advantages of high
      potency and specificity. Among alpha-emitting radionuclides that are medically
      relevant and currently available, the lead-212/bismuth-212 radionuclide pair
      could constitute an in vivo generator. Considering its short half-life (T1/2 =
      60.6 min), 212Bi can only be delivered using labelled carrier molecules that
      would rapidly accumulate in the target tumor. To expand the range of
      applications, an interesting method is to use its longer half-life parent 212Pb
      (T1/2 = 10.6 h) that decays to 212Bi. The challenge consists in keeping 212Bi
      bound to the vector after the 212Pb decay. Preclinical and clinical studies have
      shown that a variety of vectors may be used to target alpha-emitting
      radionuclides to cancer cells. Nanoparticles, notably liposomes, allow combined
      targeting options, achieving high specific activities, easier combination of
      imaging and therapy and development of multimodality therapeutic agents (e.g.,
      radionuclide therapy plus chemotherapy). The aim of this work consists in
      assessing the in vitro stability of 212Pb/212Bi encapsulation in the liposomes.
      Indeed, the release of the radionuclide from the carrier molecules might causes
      toxicity to normal tissues. To reach this goal, Asymmetrical Flow Field-Flow
      Fractionation (AF4) coupled with a Multi-Angle Light Scattering detector (MALS)
      was used and coupling with a gamma (gamma) ray detector was developed. AF4-MALS
      gamma was shown to be a powerful tool for monitoring the liposome size together
      with the incorporation of the high energy alpha emitter. This was successfully
      extended to assess the stability of 212Bi-radiolabelled liposomes in serum
      showing that more than 85% of 212Pb/212Bi is retained after 24 h of incubation at
      37  degrees C.

PMID- 30224279
TI  - Development and validation of an ultra performance liquid chromatography
      quadrupole time of flight-mass spectrometry (in MSE mode) method for the
      quantitative determination of 20 antimicrobial residues in edible muscle tissue
      of European sea bass.
AB  - A UPLC-QTOF-MS method for the simultaneous determination of 20 veterinary drug
      residues and metabolites (tetracyclines, quinolones, sulfonamides and
      diaminopyrimidines) in edible muscle plus skin tissue of European sea bass
      (Dicentrarchus Labrax) was developed. For the identification of analytes a
      positive electrospray ionization quadropole time-of flight mass spectrometer
      operating in MSE mode (UPLC-QTOF-MSE) was used. MSE mode provides high
      chromatographic resolution and accurate mass measurements in both MS and MS/MS
      modes simultaneously in a single run. Separation was achieved on a UPLC BEH C18
      (50 mm * 2.1 mm, 1.7 MUm) column in a gradient elution program of 10 min.
      Examined antibiotics were isolated easily after a simple solid-liquid extraction
      procedure with acidic acetonitrile (0.1% v/v formic acid) and Na2EDTA 0.1 M.
      Recovery rates from muscle plus skin tissue ranged from 93.8% to 107.5% for all
      targeted compounds. The detection limits and the limits of quantification ranged
      from 2.22 to 15.00 MUg/kg, and from 6.67 to 45.46 MUg/kg, respectively. The
      developed method was validated in terms of selectivity, matrix effect, linearity,
      accuracy, precision, stability and sensitivity, CCalpha and CCbeta according to
      European Union Decision 2002/657/EC. The proposed method was applied for the
      analysis of contaminated fish samples after in feed administration of
      danofloxacin mesylate.

PMID- 30224280
TI  - Preparative enantioseparation of synephrine by conventional and pH-zone-refining
      counter-current chromatography.
AB  - Synephrine, a chiral adrenergic agonist, exists as R- (more active) and S
      enantiomers (less active) that are difficult to separate because of their
      alkalinity and high polarity. Herein, we show that although this
      enantioseparation can hardly be achieved by high-performance liquid
      chromatography, acceptable preparative separation can be realized using high
      speed counter-current chromatography (HSCCC) and pH-zone-refining counter-current
      chromatography (CCC) under optimal conditions. Specifically, 23.0 mg of S
      synephrine and 25.0 mg of R-synephrine were isolated from 60.0 mg of racemic
      synephrine by conventional HSCCC, while 70.0 mg of S-synephrine and 69.0 mg of R
      synephrine were obtained from 200.0 mg of racemic synephrine by pH-zone-refining
      CCC. The pH-zone-refining CCC was identified as the most efficient
      enantioseparation technique for synephrine and can be applied for the preparative
      enantioseparation of other beta-amino alcohols.

PMID- 30224281
TI  - Detection and quantification of trace airborne transfluthrin concentrations via
      air sampling and thermal desorption gas chromatography-mass spectrometry.
AB  - A rapid thermal desorption-gas chromatography-electron ionization-mass
      spectrometry (TD-GC-EI-MS) method for airborne transfluthrin detection is
      studied. Active air sampling of 9 L over 1 h at 23  degrees C through a Tenax(r)
      loaded tube resulted in efficient capture of airborne transfluthrin. Subsequent
      thermal desorption was employed to achieve an LOD of 2.6 ppqv (parts per
      quadrillion by volume). A minimum primary desorption temperature of 300  degrees
      C is necessary for optimal recovery of sample from the Tenax(r) adsorbent. The
      matrix effects of indoor air lead to an error of 10.9% and 10.5% recovery of
      sample (10 pg and 100 pg loaded tubes, respectively). The linear range was 74
      74,000 ppqv with a correlation coefficient of 0.9981. Active air sampling of a
      novel passive release device revealed a ~150 pg/L airborne concentration gradient
      over 1 m, providing spatial characterization of the device's performance. This
      efficient method allows for the remote collection of samples and rapid analysis
      of airborne transfluthrin from industrial applications, optimization studies of
      commercial products as well as domestic/household monitoring.

PMID- 30224282
TI  - Influence of silica functionalization by amino acids and peptides on the
      stationary phases zeta potential.
AB  - In this study, the zeta potentials of silica-based stationary phases with
      chemically bonded amino acids and peptides of different types (glycine, alanine,
      phenylalanine, leucine, and aspartic acid) and chain lengths (amino acid, di- and
      tripeptides) have been measured in water/acetonitrile and water/methanol
      solutions. The zeta potential changes with ionic strength of the mobile phase
      were tested using phosphate buffer. A series of home-made stationary phases were
      also studied in different pH conditions. In order to compare how the
      modifications based on the amino acids vary from the conventional packings, pure
      silica, silica modified with aminopropyl ligands, and octadecyl groups were also
      studied. The results show that the increase of the amino acid polarity and
      sequence length causes higher zeta potential values. The changing conditions from
      acidic to basic result in shifting the zeta potential values from positive to
      negative. Depending on the environment, different ionization states of the
      chemically bonded functionalities provide different charge distribution on the
      surface of the particles.

PMID- 30224283
TI  - Fast track SSTI management program based on a rapid molecular test (GeneXpert(r)
      MRSA/SA SSTI) and antimicrobial stewardship.
AB  - PURPOSE: This study examines the impacts of a skin and soft tissue infection
      (SSTI) management program involving a rapid diagnostic algorithm (Gram stain plus
      real-time PCR, GeneXpert(r) MRSA/SA SSTI) performed directly on clinical samples
      plus antimicrobial stewardship (AMS) counseling of the responsible physician.
      METHODS: Participants were 155 consecutive adult inpatients with SSTI and good
      quality clinical samples submitted to the microbiology laboratory from April 2016
      to January 2017. Results of the rapid test and AMS recommendations were phoned
      through to the responsible physician. The comparison group was a historical
      cohort. RESULTS: Most SSTI were surgical wound infections (41.3% vs 38.1% for the
      intervention and comparison groups respectively) followed by diabetic foot (14.2%
      and 18.1%), abscesses (13.5% both) and cellulitis (12.9% both). Isolated
      microorganisms were mostly Gram-negative bacilli (two-thirds), followed by
      Staphylococcus aureus (SA). The ratio methicillin-susceptible SA (MSSA) to
      methicillin-resistant SA (MRSA) was 4:1. Improvements in the intervention cohort
      were: DOT (22.0 vs. 24.3 days, p = 0.007), treatment duration per SSTI episode
      (14.1 vs. 15.0 days, p = 0.072), treatment cost (433.1 vs. 533.3 ?, p = 0.039),
      length of stay (18.6 vs 20.7 days, p = 0.031), related mortality (1 vs. 4
      patients, p = 0.022) and Clostridium difficile infection (CDI) (4 vs. 8 patients,
      p = 0.050). In 48 cases (31.4%) in the intervention group, advice was given to
      improve empiric antibiotic treatment. CONCLUSION: This type of program could help
      adjust antibiotic treatment when inappropriate, reducing antibiotic use and
      costs, length of stay, CDI and related mortality.

PMID- 30224284
TI  - Successful treatment of prediabetes in clinical practice using physiological
      assessment (STOP DIABETES).
AB  - BACKGROUND: Of the 84 million American adults with prediabetes, over 5 to 7
      years, about 28 million progress to type 2 diabetes. We aimed to assess whether a
      real-world, pathophysiology-based, therapeutic approach could prevent development
      of type 2 diabetes in high-risk individuals. METHODS: We did a retrospective
      observational study of people at increased risk of type 2 diabetes from a
      community practice in southern California, USA. Participants had an oral glucose
      tolerance test and were assigned a risk stratification on the basis of presence
      and severity of insulin resistance, impaired beta-cell function, and glycaemia
      (ie, 1-h plasma glucose concentration of more than 8.6 mmol/L during an oral
      glucose tolerance test). Treatment was recommended on the basis of risk:
      metformin, pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonist, and
      lifestyle therapy for participants at high risk of diabetes, and metformin,
      pioglitazone, and lifestyle therapy for those at intermediate risk. Individuals
      who refused pharmacological therapy were assigned to lifestyle therapy only.
      Participants were followed up every 6 months and oral glucose tolerance tests
      were repeated at 6 months and subsequently every 2 years or sooner. The primary
      outcome of our analysis was incidence of type 2 diabetes according to the
      American Diabetes Association criteria, within the study period (2009-16). This
      study is registered with ClinicalTrials.gov, number NCT03308773. FINDINGS:
      Between Jan 1, 2009 and Dec 31, 2016, we assessed 1769 people at increased risk
      of diabetes, of which 747 (42%) were identified at high or intermediate risk and
      were recommended pharmacological treatment. Of 422 participants analysed, 28 (7%)
      progressed to type 2 diabetes (seven [5%] of 141 participants who received
      metformin, pioglitazone, and lifestyle therapy, none [0%] of 81 who received
      metformin, pioglitazone, GLP-1 receptor agonist, and lifestyle therapy, and 21
      [11%] of 200 who received lifestyle therapy only) after mean follow-up of 32.09
      months (SEM 1.24). Compared with participants who received lifestyle therapy
      only, the adjusted hazard ratio for progression to type 2 diabetes was 0.29 (95%
      CI 0.11-0.78, p=0.0009) in participants who received metformin and pioglitazone,
      and 0.12 (95% CI 0.02-0.94, p=0.04) in participants who received metformin,
      pioglitazone, and GLP-1 receptor agonist. Improved beta-cell function was the
      strongest predictor of type 2 diabetes prevention. INTERPRETATION: Progression to
      type 2 diabetes in people at high risk of diabetes can be markedly reduced with
      interventions designed to correct underlying pathophysiological disturbances (ie,
      impaired insulin secretion and resistance) in a real-world setting. FUNDING:
      None.

PMID- 30224285
TI  - Real-world diabetes prevention: from theory to practice.

PMID- 30224286
TI  - Fluorescence Interference Contrast-enabled structures improve the microarrays
      performance.
AB  - Continuous improvements of the fluorescence-based sensitivity and specificity,
      required for high throughput screening, diagnostics, and molecular biology
      studies, are usually addressed by better readout systems, or better reporting
      elements. However, while Fluorescence Interference Contrast (FLIC), which
      modulates the fluorescence by materials-based parameters, has been used for
      decades to measure biomolecular interactions at nanometer-precision, e.g., for
      the study of molecular motors and membrane processes, it has been seldom used for
      high throughput or diagnostic microdevices. Moreover, the amplification of both
      the fluorescence signal, modulated by vertically-nano-calibrated structures, and
      the signal/background, modulated by laterally-micro-calibrated structures, has
      not been explored. To address this synergy, structures comprising optically
      transparent silicon oxide, tens of micrometers-wide and with thicknesses in the
      low hundreds of nanometers, which are able to promote the formation of standing
      waves if patterned on a reflective material, have been designed, fabricated and
      tested, for the use in DNA- and protein arrays. The light emitted by a
      fluorophore placed on top of the structures and reflected by a bottom mirror
      surface, e.g., silicon, platinum, is physically constrained to a region defined
      lithographically, both vertically and laterally, i.e., micro-pillars and -wells,
      resulting in an accurate identification and quantification of fluorescence. The
      signal/noise ratio on micro-/nano-structured substrates is comparable to that
      measured on planar substrates, but the physical confinement of the microarray
      spots results in a considerable increase of the intra-feature uniformity.

PMID- 30224287
TI  - Improved microfluidic platform for simultaneous multiple drug screening towards
      personalized treatment.
AB  - Development of new targeted therapies is a challenge in the battle against
      cancer. Although a variety of treatments is currently available, there is no
      technique for rapidly evaluating the response of cancer patients to the drug. In
      this work, a microfluidic platform for the real-time simultaneous analysis of the
      success rate of different nanoparticle based chemotherapeutic drugs is presented.
      Based on a previous planar chamber and a reported sensitivity enhancing strategy,
      linear and cross shape microstructures were integrated into the chamber dome of
      the microfluidic polydimethylsiloxane and glass platform in order to provide a
      higher fluid mixing and treatment-cell interaction. Several methotrexate (MTX)
      based treatments (free MTX, MTX loaded Lecithin-PVA nanoparticles, MTX loaded
      Lecithin-Tween 80 nanoparticles) as well as their respective controls (cell media
      and both blank nanoparticles) were recirculated through the microchamber over an
      osteosarcoma cell monolayer. These nanovehicles reduced cell population to less
      than 20% (LEC-PVA nanoparticles) and 2.3% (LEC-Tween nanoparticles),
      demonstrating that nanoparticles are a promising target therapy for cancer
      treatment. Moreover, microstructured platforms demonstrated a higher efficacy in
      the drug-screening process: due to the liquid folding a higher amount of
      nanoparticles was internalized by the cells and, therefore, results were observed
      faster. In fact, the time required to reduce cell viability to the half was
      nearly a 75% faster. Furthermore, this microfluidic platform offers the
      capability to test up to five different drugs simultaneously, making it a
      powerful tool to evaluate the effect of multiple drugs and determine the most
      effective and personalized treatment.

PMID- 30224288
TI  - Message to world leaders: we cannot end tuberculosis without addressing the
      social and economic burden of the disease.

PMID- 30224289
TI  - Hydrodynamic cavitation assisted degradation of persistent endocrine-disrupting
      organochlorine pesticide Dicofol: Optimization of operating parameters and
      investigations on the mechanism of intensification.
AB  - Dicofol, a recommended Stockholm convention persistent organic pollutants (POPs)
      candidate is well known for its endocrine disruptive properties and has been
      extensively used as an organochlorine pesticide worldwide. The hydrodynamic
      cavitation (HC) treatment of Dicofol in aqueous media induced by a liquid whistle
      hydrodynamic cavitaion reactor (LWHCR) has been investigated while considering
      important parameters such as inlet pressure, initial concentration of Dicofol,
      solution temperature, pH, addition of H2O2 and radical scavenger for the extent
      of degradation. The pseudo-first-order degradation rate constant (k) was
      determined to be 0.073 min-1 with a cavitational yield of 1.26 * 10-5 mg/J at
      optimum operating conditions and a complete removal of Dicofol was achieved
      within 1 h of treatment. Considering the removal rate and energy efficiency, the
      optimal inlet pressure was found to be 7 bar, resulting in a cavitation number of
      0.17. High performance liquid chromatography (HPLC) and Gas chromatography mass
      spectroscopy (GC-MS) analyses indicated a sharp decline in the concentration of
      Dicofol with treatment time and indicated the presence of degraded products. An
      85% total organic carbon (TOC) removal was achieved within 1 h of treatment time,
      demonstrating successful mineralization of Dicofol. The obtained results suggest
      that the degradation of Dicofol followed thermal decomposition and successive
      recombination reactions at bubble-vapor interface. Overall, the attempted
      hydrodynamic cavitation demonstrated successful and rapid removal of endocrine
      disruptive chemicals such as Dicofol and is expected to provide efficient
      solution for wastewater treatment.

PMID- 30224290
TI  - Sono-nano chemistry: A new era of synthesising polyhydroxylated carbon
      nanomaterials with hydroxyl groups and their industrial aspects.
AB  - The main objective of this review is to derive the salient features of previously
      developed ultrasound-assisted methods for hydroxylating graphene and
      Buckminsterfullerene (C60). The pros and cons associated to ultrasound-assisted
      synthesis of hydroxy-carbon nanomaterials in designing the strategical methods
      for the industrial bulk production are also discussed. A guideline on the
      statistical methods has also been considered to further provide the scopes
      towards the application of the previously reported methods. Irrespective of many
      useful methods that have been developed in order to functionalize C60 and
      graphene by diverse oxygenated functional groups e.g. epoxide, hydroxyl, carboxyl
      as well as metal/metal oxide via a combination of organic chemistry and
      sonochemistry, there is no report dealing exclusively on the application of
      ultrasonic cavitation particularly to synthesising polyhydroxylated carbon
      nanomaterials. On this context, this review emphasizes in investigating the
      critical aspects of sono-nanochemistry and the statistical approaches to optimize
      the variables in the sonochemical process towards a large-scale synthesis of
      polyhydroxylated graphene and C60.

PMID- 30224291
TI  - What to do when good-quality embryos repeatedly fail to implant.
AB  - Recurrent implantation failure (RIF) is very distressing for couples and
      frustrating for their clinicians who seek to find a solution. RIF is defined as
      the failure to achieve a clinical pregnancy following the transfer of at least
      four good-quality embryos in a minimum of three fresh or frozen cycles in a woman
      of age below 40 years. An agreed local protocol regarding how couples with RIF
      should be further investigated and managed should be in place. Ovarian function
      should be assessed by measuring antral follicle count, FSH, and AMH. Chromosomal
      testing of the couple is advised to exclude genetic abnormalities that may lead
      to RIF. Various uterine pathologies including fibroids, endometrial polyps,
      congenital anomalies, and intrauterine adhesions should be excluded by
      ultrasonography and hysteroscopy. Hydrosalpinges are a recognized cause of
      implantation failure and should be excluded by hysterosalpingogram, and if
      necessary, laparoscopy should be performed to confirm or refute the diagnosis.
      Consideration should be given to preimplantation genetic screening (PGS) and the
      adoption of a "freeze-all" protocol. Treatment offered should be evidence based,
      aimed at improving embryo quality or endometrial receptivity. Gamete donation or
      surrogacy may be necessary if there is no realistic chance of success with
      further IVF attempts.

PMID- 30224292
TI  - Progress and pitfalls in measuring HIV preexposure prophylaxis coverage in the
      United States.

PMID- 30224293
TI  - Personalized gene and cell therapy for Duchenne Muscular Dystrophy.
AB  - Dystrophinopathies are diseases caused by mutations in the Duchenne Muscular
      Dystrophy gene (DMD) encoding the dystrophin protein. Depending on the type of
      mutation, patients develop either the severe DMD or the milder Becker Muscular
      Dystrophy. Although substantial effort was made, the pathophysiology and
      variation in disease severity are still poorly understood. During the last two
      decades, relentless efforts were made to develop therapeutic strategies. Among
      these, gene therapy and cell replacement therapy appear very promising. These
      approaches are based on the replacement and/or repair of the mutated DMD gene or
      transcript at the molecular level, or at the cellular level via replacement of
      the damaged muscle cells. While highly successful in animal models, these
      therapies showed only modest efficacy in human clinical trials. More importantly,
      variable effects were observed in patients carrying the same mutation, suggesting
      that several factors (e.g., genetic modifiers, environmental factors) can affect
      treatment outcomes. In this review, we will describe recent advancements and new
      approaches of gene and cell therapies for dystrophinopathies that pave the way
      for a medicine "a la carte".

PMID- 30224294
TI  - Synthesis, convergence, and differences in the entangled histories of
      cytogenetics in medicine: A comparative study of Canada and Mexico.
AB  - Most historians of science and medicine agree that medical interest in genetics
      intensified after 1930, and interest in the relationship of radiation damage and
      genetics continued and expanded after World War II. Moreover, they maintain that
      the synthesis and convergence of human genetics and cytological techniques in
      European centers resulted in their dissemination to centers in the United States,
      resulting in a new field of expertise focused on medicine and clinical research,
      known as cytogenetics. In this article, we broaden the scope of the inquiry by
      showing how the early histories of cytogenetics in Canada and Mexico unfolded
      against strikingly different backgrounds in clinical research and the delivery of
      health care. We thus argue that the field of cytogenetics did not emerge in a
      straightforward manner and develop in the same way in all countries. The article
      provides a brief background to the history of human cytogenetics, and then
      outlines key developments related to the early adoption of cytogenetics in Canada
      and Mexico. Conclusions are then drawn using comparisons of the different ways in
      which local determinants affected adoption. We then propose directions for future
      study focused on the ways in which circuits of practices, collaborative research,
      and transfers of knowledge have shaped how cytogenetics has come to be organised
      in medicine around the world.

PMID- 30224295
TI  - A Pediatric Fruit and Vegetable Prescription Program Increases Food Security in
      Low-Income Households.
AB  - OBJECTIVE: To assess change in household food security associated with
      participation in a pediatric fruit/vegetable prescription program. METHODS: The
      researchers analyzed clinic-based, fruit/vegetable prescription program data for
      578 low-income families, collected in 2013-2015, and calculated changes in food
      security (summative score; high/low/very low; and individual US Department of
      Agriculture measures). RESULTS: Of participating households, 72% increased their
      summative score over the course of the program. In adjusted regression models,
      participants had higher change scores with 5 or 6 clinical visits, compared with
      1 or 2 visits (beta = .07; 95% confidence interval, 0.01-0.14), and college
      education of the primary caretaker, compared with less than college (beta = .05;
      95% confidence interval, 0.01-0.09). Select clinic sites (but neither visit nor
      redemption proportions) significantly contributed to change score variance. All
      US Department of Agriculture measures saw significant increases. CONCLUSIONS AND
      IMPLICATIONS: Fruit/vegetable prescription programs may help providers address
      patients' food insecurity. Further research using experimental designs and
      implementation science could build the case to incorporate programs into
      practice.

PMID- 30224296
TI  - Comparison between groove carcinoma and groove pancreatitis.
AB  - BACKGROUND/OBJECTIVES: The pancreatoduodenal groove (anatomical groove) is a
      potential space bordered by the head of the pancreas, duodenum, and common bile
      duct. Discerning between groove carcinoma (GC) and groove pancreatitis (GP) is
      often difficult, but clinically important. We retrospectively analyzed and
      compared the findings of computed tomography (CT), laboratory tests, and
      endoscopic ultrasound-fine needle aspiration (EUS-FNA) for GC and GP. METHODS: GC
      (n = 36) and GP (n = 44) patients at Asan Medical Center from January 1, 2000, to
      May 31, 2017 were retrospectively reviewed. MDCT findings, baseline
      characteristics, laboratory test results, and EUS and EUS-FNA findings of GC and
      GP patients were compared. RESULTS: CT showed no significant difference in groove
      enhancement between the groups. Mass-like lesions, cystic groove lesions, and
      calcification were observed in 86.1% and 15.9%, 38.9% and 75%, and 2.8% and 29.5%
      of GC and GP patients, respectively. Patients were tested for total bilirubin
      (GC: 2.0 vs. GP: 0.6 mg/dL), cancer antigen 19-9 (CA19-9) (GC: 76 vs. GP: 12.5
      U/mL), and carcinoembryonic antigen (GC: 2.4 vs. GP: 2 ng/mL). Three GP patients
      died, and one GP patient was diagnosed with GC. However, among 30 GC patients
      with at least 1-year follow-up, 20 died. In multivariate logistic regression,
      CA19-9, and mass-like lesion on multidetector CT (MDCT) were discriminating
      factors between GC and GP. Among 23 (10 GC, 13 GP) patients who underwent EUS
      FNA, the diagnostic sensitivity, specificity, positive predictive value, negative
      predictive value, accuracy of EUS-FNA were 90%, 100%, 100%, 92.86%, and 95.65%,
      respectively. CONCLUSIONS: Several MDCT and laboratory findings favor GC over GP.
      EUS-FNA should be considered in patients with elevated CA19-9 levels and mass
      like lesions on MDCT.

PMID- 30224297
TI  - Weight Loss in Adolescents After Bariatric Surgery: A Systematic Review.
AB  - INTRODUCTION: Bariatric surgery is a treatment option for the obese adolescent.
      There are three primary surgical procedures: the bypass, sleeve gastrectomy, and
      lap band. The most recent literature was reviewed to examine changes in weight,
      comorbidities, and complications after bariatric surgery in the adolescent.
      METHOD: A systematic search was performed to identify original research articles
      published in the United States between the years of 2000 and 2017 with patients
      between the ages of 11 and 21years that provided greater than 30 days of results.
      RESULTS: A total of 23 articles were identified. Weight loss, improvement in
      comorbidities, and complications after all procedures were reported. DISCUSSION:
      Outcomes were not reported in a standardized fashion, creating much difficulty in
      interpreting and comparing results. The sleeve gastrectomy is increasing in
      incidence, whereas the lap band is decreasing. Further research is needed to draw
      more definitive conclusions regarding long-term results in the adolescent
      undergoing bariatric surgery.

PMID- 30224298
TI  - CircBA9.3 supports the survival of leukaemic cells by up-regulating c-ABL1 or BCR
      ABL1 protein levels.
AB  - The unchecked tyrosine kinase activity of BCR-ABL1 contributes to the immortality
      of leukaemic cells. Therefore, this oncogene is a highly important therapeutic
      target for chronic myelogenous leukaemia (CML). Tyrosine kinase inhibitors (TKIs)
      are an excellent drug treatment for CML patients. However, there are still some
      patients who are not responsive to TKIs. We found that a novel circular RNA
      (circRNA), named circBA9.3, is derived from BCR-ABL1. CircBA9.3 can efficiently
      promote the proliferation and inhibit apoptosis of cancer cells. In addition,
      some patients with TKI resistance have elevated circBA9.3 expression, which is
      positively correlated with the level of BCR-ABL1. Furthermore, circBA9.3 is
      predominantly located in the cytoplasm and enhances c-ABL1 and BCR-ABL1
      oncoprotein expression. Thus, circBA9.3 is a molecule associated with increased
      tyrosine kinase activity that promotes resistance against TKI therapy. In this
      study, we provided a new potential target for the treatment of TKI-resistant CML
      patients.

PMID- 30224300
TI  - Attitudes toward 'Disorders of Sex Development' nomenclature among physicians,
      genetic counselors, and mental health clinicians.
AB  - INTRODUCTION: In 2006, nomenclature referencing atypical sex development (i.e.,
      'intersex') was updated, and the term disorder of sex development (DSD) was
      formally introduced. Clinicians, patients, and parents, however, have not
      universally accepted the new terminology, and some continue to use different
      nomenclature. This inconsistency in terminology can lead to confusion among
      clinicians and patients, affect clinician-patient relationships, and interfere
      with the recommended multidisciplinary model for DSD care. OBJECTIVE: This study
      sought to (1) evaluate frequency of use and comfort with specific DSD
      terminology, (2) assess why clinicians are not using specific terms, and (3)
      determine what terms are being heard within the medical community and by the
      public in a sample of physicians, genetic counselors, and licensed mental health
      clinicians. STUDY DESIGN: A Web-based survey assessing the use of DSD terminology
      was distributed to endocrinologists, urologists, genetic counselors, and mental
      health clinicians. The survey assessed frequency of use and comfort with specific
      terms, negative experiences related to specific nomenclature use, and the context
      in which terms are used (e.g. case conference, literature, patient/parents, and
      media). A qualitative analysis of open-ended responses was conducted to
      characterize reasons for avoiding specific terms. RESULTS: The survey was
      completed by 286 clinicians. There were significant differences between
      specialties in comfort and frequency of use of specific terms, and significant
      differences were based on clinician gender, patient volume, length of time in
      practice, and practice setting. The study results also showed a difference in the
      nomenclature used within the medical community versus the media. DISCUSSION:
      Study findings are consistent with previous research exploring medical
      professionals' use of the new term: disorder of sex development. However, there
      continues to be inconsistency in the uptake of this new terminology. Words that
      have been purposed in the literature to replace disorder, such as difference and
      variation, would be accepted by clinicians, and the word divergent would not.
      This study expands on the existing literature documenting high uptake of disorder
      of sex development nomenclature among medical professionals. In addition, this
      study demonstrates that the most common diagnostic terms used by the medical
      community are not the same terms being presented to the public by the media.
      CONCLUSION: Medical professionals have varying preferences for terminology use
      when describing DSD, which can affect patient care. These results can be used in
      the future to compare with what patients and advocates prefer to develop a more
      universally accepted approach to nomenclature.

PMID- 30224301
TI  - Onabotulinum toxin A in children with refractory idiopathic overactive bladder:
      medium-term outcomes.
AB  - INTRODUCTION: Botulinum toxin-A (BtA) has been used for refractory idiopathic
      overactive bladder (IOAB) in children. Data on the optimum dose success rates,
      duration of effect, complications and medium-term outcomes are limited. This
      study aims to analyse the authors' experience to provide medium-term results of
      BtA in symptomatic refractory patients. MATERIALS AND METHODS: Patients with
      refractory IOAB who were treated with BtA (Botox(r)) were retrospectively
      analysed. All patients had urodynamic study before treating with BtA. Group A had
      low-dose BtA (LDBtA) at 5 units/kg (maximum 150 units), and Group B had high-dose
      BtA (HDBtA) at 10 units/kg (maximum 300 Units). Post-BtA clinical response,
      functional bladder capacity (FBC) and postvoid residual (PVR) were assessed in
      addition to the duration of response. RESULTS: Thirty-nine patients, 11 male and
      28 female, were analysed. Forty-six percentage had symptom improvement (73% of
      males and 36% of females [P = 0.072, ns]). The difference in response rates
      between LDBtA and HDBtA was not statistically significant (P = 0.684). Increase
      in total bladder capacity (TBC) was greater in those given HDBtA (P <= 0.001),
      but the increase in FBC was not different between the groups, due to greater PVRs
      in the HDBtA group. Nine patients (23%) developed UTI; however, six of these
      patients suffered with UTI pre-BtA as well. Only three were asymptomatic after a
      single treatment with BtA. The remainder required further BtA or oral
      anticholinergic therapy. At a median follow-up of 35.4 months (interquartile
      range [IQR] 25.2-46.6), 12 (31%) were asymptomatic and off all therapy, 18 (46%)
      were still symptomatic despite therapy and 9 (23%) had their symptoms controlled
      on continuing treatment. DISCUSSION AND CONCLUSIONS: Botulinum toxin-A improves
      symptoms in 46% of children after the first injection in refractory IOAB.
      Although HDBtA resulted in greater increase in bladder capacity, it conferred no
      advantage in terms of success rate or duration of response. Five units/kg may be
      an optimum dose to use as a first treatment with the understanding that some
      patients will require a higher dose. And, there will be a cohort of patients who
      need a dose lower than 5 units/kg. A higher dose is more likely to lead to PVR
      leading to urine stasis and UTIs. The success of BtA only lasts until its effect
      wears off, and the majority of this cohort (36/39) required continuing treatment
      with repeat BtA or anticholinergic agents. However, it remains a useful option in
      patients who are intolerant or unresponsive to anticholinergic medication with
      symptomatic resolution in 30% at medium-term follow-up.

PMID- 30224299
TI  - Hepatic leptin receptor expression can partially compensate for IL-6Ralpha
      deficiency in DEN-induced hepatocellular carcinoma.
AB  - OBJECTIVE: The current obesity pandemic represents a major health burden, given
      that it predisposes to the development of numerous obesity-associated disorders.
      The obesity-derived adipokines not only impair systemic insulin action but also
      increase the incidence of hepatocellular carcinoma (HCC), a highly prevalent
      cancer with poor prognosis. Thus, worldwide incidences of HCC are expected to
      further increase, and defining the molecular as well as cellular mechanisms will
      allow for establishing new potential treatment options. The adipose tissue of
      obese individuals increases circulating leptin and interleukin-6 (IL-6) levels,
      which both share similar signaling capacities such as Signal Transducer and
      Activator of Transcription 3 (STAT3) and Phosphoinositide 3-kinase (PI3K)/Akt
      activation. While mouse models with deficient IL-6 signaling show an ameliorated
      but not absent Diethylnitrosamine (DEN)-induced HCC development, the morbid
      obesity in mice with mutant leptin signaling complicates the dissection of
      hepatic leptin receptor (LEPR) and IL-6 signaling in HCC development. Here we
      have investigated the function of compensating hepatic LEPR expression in HCC
      development of IL-6Ralpha-deficient mice. METHODS: We generated and characterized
      a mouse model of hepatic LEPR deficiency that was intercrossed with IL-6Ralpha
      deficient mice. Cohorts of single and double knockout mice were subjected to the
      DEN-HCC model to ascertain liver cancer development and characterize metabolic
      alterations. RESULTS: We demonstrate that both high-fat diet (HFD)-induced
      obesity and IL-6Ralpha deficiency induce hepatic Lepr expression. Consistently,
      double knockout mice show a further reduction in tumor burden in DEN-induced HCC
      when compared to control and single LepRL-KO/IL-6Ralpha knock out mice, whereas
      metabolism remained largely unaltered between the genotypes. CONCLUSIONS: Our
      findings reveal a compensatory role for hepatic LEPR in HCC development of IL
      6Ralpha-deficient mice and suggest hepatocyte-specific leptin signaling as
      promoter of HCC under obese conditions.

PMID- 30224302
TI  - Dietary quality influences body composition in overweight and obese pregnant
      women.
AB  - BACKGROUND & AIMS: Excessive adiposity and gestational weight gain (GWG) have
      been linked with maternal and offspring morbidity. We investigated the relation
      of maternal diet, physical activity and GWG on body composition in overweight and
      obese pregnant women. METHODS: Fat mass (FM) and fat free mass (FFM) of 110
      overweight and obese pregnant women were measured by air displacement
      plethysmography in early and late pregnancy (mean 13.5 and 35.3 gestational
      weeks). At the same time points, the quality of overall diet was assessed by
      validated index of diet quality (IDQ) questionnaire (score < 10/15 denotes poor
      dietary quality and score >= 10/15 denotes good dietary quality), nutrient
      intakes by 3-day food diaries, and physical activity by questionnaire. Weight
      gain between early and late pregnancy was compared to the gestational weight gain
      guidelines issued by Institute of Medicine. RESULTS: Of the women, 77% gained
      more weight than recommended; this was related to greater dietary fat consumption
      (80 +/- 21 g/day vs. 67 +/- 11 g/day, p = 0.010) and greater increase in FM (2.7
      +/- 3.0 kg vs. -1.0 +/- 2.4 kg, p < 0.001) compared to women with ideal GWG.
      Dietary protein intake (g) correlated positively with FFM at both time points
      (early pregnancy: r = 0.31, p < 0.002, late pregnancy: r = 0.39, p < 0.001).
      Women with higher dietary quality index score had more FFM, compared to women
      with lower dietary quality (early pregnancy FFM: 48.8 +/- 5.8 kg vs. 45.8 +/- 4.7
      kg, p = 0.004, late pregnancy FFM: 56.1 +/- 6.4 kg vs. 53.4 +/- 5.6 kg, p =
      0.025). No correlations were detected between total energy intake or physical
      activity and FM or FFM at early or late pregnancy. CONCLUSIONS: Body composition
      changes from early to late pregnancy were related to the amount of weight gained
      and overall dietary quality during pregnancy. Higher dietary quality and protein
      intake were associated with greater FFM, while dietary fat intake was related to
      excess weight gain. Identification of these dietary determinants of body
      composition and weight offers new targets for dietary counseling of pregnant
      women and thus potential for ensuing health benefits through reduced adiposity.

PMID- 30224303
TI  - A multicentre development and evaluation of a dietetic referral score for
      nutritional risk in sick infants.
AB  - BACKGROUND & AIMS: Unrecognized nutritional issues may delay recovery in
      hospitalized infants. It has been proposed that nutritional risk screening should
      be performed at hospital admission, but few tools include infants. The aim of
      this study was to develop and test a tool to identify sick infants in need of
      dietetic input. METHODS: Hospitalised infants were recruited from hospitals in
      the United Kingdom (UK), Greece and Iran. Weight, skinfold thickness and mid
      upper arm circumference (MUAC) were measured, with detailed dietetic assessment
      in the UK and Greece. Simple screening questions were used in the UK cohort to
      formulate a score (infant early nutrition warning score-iNEWS) which was then
      validated in the Greek and Iranian groups. RESULTS: After dietetic assessment, 20
      (9.6%) UK and 22 (22%) Greek infants were rated as needing dietetic input.
      Underweight, poor weight gain/loss and reduced intake were all independent
      predictors of perceived need for dietetic input in stepwise multivariate
      regression analysis. The score based on these items (iNEWS), had 84% sensitivity,
      91% specificity and 49% positive predictive value to predict need for dietetic
      input in the UK cohort. In the Greek cohort this was 86%, 78% and 53%
      respectively. In all three countries, infants with high iNEWS had significantly
      lower average skinfold thickness (between -1 and -1.8 SD, p < 0.0001) and MUAC
      (between -1.8 and -2 SD, p < 0.0001) than those at low risk. CONCLUSIONS: iNEWS,
      a simple nutritional risk tool, identifies most hospitalised infants who need
      dietetic input. CLINICAL TRIAL REGISTRATION:
      https://clinicaltrials.gov/ct2/show/NCT03323957.

PMID- 30224304
TI  - Association between phase angle from bioelectrical impedance analysis and level
      of physical activity: Systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the relationship between physical activity and phase
      angle. DESIGN: Systematic Review and Meta-analysis. DATA SOURCES: Electronic
      searches of MEDLINE (via PUBMED), EMBASE, Cochrane Central Register of Controlled
      Trials (CENTRAL, The Cochrane Library), SciELO, LILACS, SPORTDiscus, Scopus, and
      Web of Science from inception to December 10th, 2017. ELIGIBILITY CRITERIA FOR
      SELECTING STUDIES: The PICOS strategy was defined, in which "P" corresponded to
      participants of any age, sex or ethnicity, "I" indicated any type of physical
      activity program, "C" denoted lack of exercise or irregular physical activity,
      "O" corresponded to the phase angle obtained by bio-impedance, and "S" indicated
      longitudinal or cross-sectional studies. RESULTS: In cross-sectional studies the
      phase angle was higher among the active individuals (MD = 0.70; 95% CI: 0.48,
      0.92, P < 0.001), with low heterogeneity (I2 = 0%; P = 0.619). In longitudinal
      studies, the mean of the difference of phase angles from the baseline was
      significantly higher for the active group than the control group (MD = 0.30; 95%
      CI: 0.11, 0.49, P = 0.001), with low heterogeneity (I2 = 13%, P = 0.331). No
      evidence of publication bias was found and the overall risk of bias was moderate
      to high. SUMMARY/CONCLUSION: The positive association of physical activity with
      phase angle reinforces the importance of routinely including exercise in health
      care. We also identified the need for further studies to define with different
      types, intensities and frequencies of exercises should be conducted in order to
      find the best dose-effect relationship.

PMID- 30224305
TI  - Effects of dietary omega-3 fatty acids on bones of healthy mice.
AB  - BACKGROUND & AIMS: Altering the lipid component in diets may affect the incidence
      of metabolic bone disease in patients dependent on parenteral nutrition.
      Consumption of polyunsaturated fatty acids (PUFA) can impact bone health by
      modulating calcium metabolism, prostaglandin synthesis, lipid oxidation,
      osteoblast formation, and osteoclastogenesis. The aim of this study was to
      evaluate the dietary effects of PUFA on murine bone health. METHODS: Three-weeks
      old male (n = 30) and female (n = 30) C57BL/6J mice were randomized into one of
      three dietary groups. The diets differed only in fat composition: soybean oil
      (SOY), rich in omega-6 PUFA; docosahexaenoic acid alone (DHA), an omega-3 PUFA;
      and DHA with arachidonic acid, an omega-6 PUFA, at a 20:1 ratio (DHA/ARA). After
      9 weeks of dietary treatment, femurs were harvested for micro-computed
      tomographic analysis and mechanical testing via 3-point bending. Separate mice
      from each group were used solely for serial blood draws for measurement of
      biomarkers of bone formation and resorption. RESULTS: At the microstructural
      level, although some parameters in cortical bone reached differences that were
      statistically significant in female mice, these were too small to be considered
      biologically relevant. Similarly, trabecular bone parameters in male mice were
      statistically different in some dietary groups, although the biological
      interpretation of such subtle changes translate into a lack of effect in favor of
      any of the experimental diets. No differences were noted at the mechanical level
      and in blood-based biomarkers of bone metabolism across dietary groups within
      gender. CONCLUSIONS: Subtle differences were noted at the bones' microstructural
      level, however these are likely the result of random effects that do not
      translate into changes that are biologically relevant. Similarly, differences
      were not seen at the mechanical level, nor were they reflected in blood-based
      biomarkers of bone metabolism. Altogether, dietary consumption of PUFA do not
      seem to affect bone structure or metabolism in a healthy model of growing mice.

PMID- 30224306
TI  - Vitamin D status during pregnancy and in cord blood in a large prospective French
      cohort.
AB  - BACKGROUND & AIMS: Vitamin D status during pregnancy and in newborns has never
      been studied in France. This study aims at determining the vitamin D status
      during the first and third trimesters of pregnancy (T1, T3) and in cord blood
      (CB) in the middle-north of France. METHODS: We conducted a prospective cohort
      study in five French centers (latitude 47.22 to 48.86 degrees N). Serum 25(OH)
      vitamin D (25(OH)D) concentrations were measured using a radioimmunoassay during
      T1, T3 and in CB. According to the French guidelines, pregnant women received
      cholecalciferol, 100,000 IU, in the seventh month. RESULTS: Between April 2012
      and July 2014, 2832 women were included, of whom 2803 were analyzed (mean +/- SD
      age: 31.5 +/- 5.0 years; phototypes 5-6: 21.8%). Three and 88.6% of participants
      received supplementation during the month before inclusion and in the seventh
      month, respectively. At T1, T3, and CB, mean 25(OH)D concentrations were 21.9 +/-
      10.4, 31.8 +/- 11.5, and 17.0 +/- 7.2 ng/mL, respectively, and 25(OH)D was <20
      ng/mL in 46.5%, 14.0%, and 68.5%, respectively. At T1, body mass index >=25
      kg/m2, dark phototypes, sampling outside summer, and no supplementation before
      inclusion were independently associated with vitamin D insufficiency (25(OH)D <
      20 ng/mL). Women who received cholecalciferol supplementation in month 7 had
      higher 25(OH)D at T3 than non-supplemented women (32.5 +/- 11.4 versus 25.8 +/-
      11.4 ng/mL, p = <0.001) and marginally higher 25(OH)D in CB (17.2 +/- 7.2 versus
      15.5 +/- 7.1 ng/mL, p = 0.004). CONCLUSIONS: Despite the recommended
      supplementation, vitamin D insufficiency is frequent during pregnancy and in
      newborns in France.

PMID- 30224307
TI  - Laryngeal Web as a Possible Cause for Nonabsorption of Vocal Nodules in Boys
      After Puberty.
AB  - OBJECTIVES: Vocal nodules are frequent in children and tend to be reabsorbed
      after puberty, especially in boys. The aims of the present study were to analyze
      the progression of nodules in boys after puberty and to investigate the role of
      microweb in the persistence of these lesions. METHODS: Clinical and
      videolaryngoscopy evaluations were carried out in boys with vocal nodules treated
      between 2009 and 2016, followed up to the age of 17 years or until remission of
      symptoms and reabsorption of the nodules. Boys with vocal nodules who underwent
      regular vocal therapy are included in the study. The outcomes were remission of
      symptoms and of the nodular lesions. RESULTS: A total of 34 boys with vocal
      nodules were diagnosed, of which 21 completed follow-up. Mean age of the first
      evaluation was 9 years (5-11 years) and of end of treatment was 14 years (13-18
      years). Mean number of videolaryngoscopy per child was five. After adolescence
      there was complete remission of symptoms and of the lesions in 15 children
      (71.4%), partial remission in four (19.0%), and no remission of symptoms and of
      the lesions in two cases. In these two, videolaryngoscopy identified the presence
      of microweb and nodules. CONCLUSIONS: Favorable reabsorption of the vocal nodules
      after adolescence was observed in the majority of the boys who underwent voice
      therapy; however, in two cases there was no remission of symptoms and of the
      lesions. The unfavorable course can be attributed to anterior laryngeal
      microwebs.

PMID- 30224308
TI  - Safety and Immunogenicity of a Nonadjuvant Human Papillomavirus Type 6 Virus-like
      Particle Vaccine in Recurrent Respiratory Papillomatosis.
AB  - OBJECTIVES: To assess the safety and immunogenicity of a nonadjuvant human
      papillomavirus (HPV) type 6 L1 virus-like particle (VLP) vaccine in recurrent
      respiratory papillomatosis (RRP) in local Chinese patients. METHODS: Patients
      with RRP who had undergone surgical treatment before intramuscular administration
      of an escalating dose of HPV type 6 L1 VLPs (1, 5, and 25 ug at 4 weekly
      intervals) as part of their treatment were followed up for more than 10 years.
      Efficacy was assessed by detecting the vaccine-induced type-specific antibody
      titer, calculating the intersurgical interval, and observing recurrence or
      remission of papillomas after receiving the vaccine. RESULTS: Nonadjuvant HPV
      vaccine was generally well tolerated, with no serious vaccine-related adverse
      episodes. It induced seroconversion for each vaccine-related HPV type. At week 12
      (4 weeks after injecting 25 ug), the vaccine-induced type-specific antibody titer
      was significantly high. Analysis of all patients found a significant increase in
      the intersurgical interval and decrease in the scores. One patient (16.7%;
      female) experienced complete remission. Five patients (83.3%) (two males and
      three females) experienced partial remission. In total, complete or partial
      remission was achieved in six (100%) patients. CONCLUSIONS: Administration of
      nonadjuvant HPV type 6 L1 VLPs vaccine to RRP was generally well tolerated and
      highly immunogenic.

PMID- 30224309
TI  - Hearing Aid Use and Auditory Verbal Therapy Improve Voice Quality of Deaf
      Children.
AB  - BACKGROUND: Adequate phonation is self-regulated by auditory feedback. Children
      with bilateral profound hearing loss (PHL) lack this feedback resulting in
      abnormal voice. Adequate hearing aid use and auditory-verbal therapy (AVT) may
      improve voice quality in deaf children. OBJECTIVE: To study whether hearing aid
      use and AVT approach improve acoustic parameters of voice of children with
      bilateral PHL. MATERIALS AND METHODS: Nineteen children with bilateral PHL were
      studied. Age range 2-5 years (X = 53.04 months; SD = 9.54). All children were
      fitted with hearing aids according to auditory testing and they underwent a 1
      year auditory habilitation period using the AVT approach. Acoustic analysis of
      voice including F0, shimmer, and jitter was performed at the onset and at the end
      of the auditory habilitation period. Final acoustic data were compared to a
      matched control group of 19 children, age range 2-5 years (X = 52.85; SD = 9.74)
      with normal hearing. RESULTS: Mean fundamental frequency (F0) was significantly
      increased after AVT intervention. Shimmer and jitter significantly (P < 0.05)
      improved after the intervention period. However, despite the improvements, mean
      F0 at the end of the intervention period was still significantly (P < 0.05)
      decreased as compared to controls. Also, mean shimmer and jitter at the end of
      the habilitation period were still significantly (P < 0.05) higher as compared to
      controls. CONCLUSIONS: The results of this preliminary study suggest that hearing
      aid use and auditory habilitation with AVT approach improved acoustic voice
      parameters of children with PHL. However, acoustic parameters persisted abnormal
      as compared to matched normal hearing controls. AVT approach and regular hearing
      aid use seem to be safe and reliable clinical tools for improving voice quality
      of children with PFL.

PMID- 30224310
TI  - Survey of ticks in French Guiana.
AB  - In this study, we examine the current pattern of tick diversity and host use in
      French Guiana, South America, from 97 sampling localities encompassing peri
      urban, rural and natural habitats. We collected 3395 ticks, including 1485
      specimens from 45 vertebrate species (humans, domestic and wild animals) and 1910
      questing specimens from vegetation. Morphological examinations identified 22
      species belonging to six genera: Amblyomma (16 species), Rhipicephalus (two
      species), Ixodes (one species), Dermacentor (one species), Haemaphysalis (one
      species), Ornithodoros (one species). To facilitate future identification, we
      produced a bank of pictures of different stages for all these species. Taxonomic
      identification was then confirmed by molecular characterization of two
      mitochondrial genes, cytochrome c oxidase CO1 and 16S rDNA. Eleven of the 22
      reported species were collected on humans, six on domestic animals and 12 on wild
      animals. The most widespread tick species collected were A. cajennense sensu
      stricto and, to a lesser extent, A. oblongoguttatum; both of these species were
      frequently found on humans. We used these results to discuss the tick-associated
      risks for human and animal health in French Guiana.

PMID- 30224311
TI  - Safety of same-day discharge after percutaneous coronary intervention with
      orbital atherectomy.
AB  - BACKGROUND: Severely calcified lesions present many challenges to percutaneous
      coronary intervention (PCI). Orbital atherectomy (OA) aids vessel preparation and
      treatment of severely calcified coronary lesions. Same-day discharge (SDD) after
      PCI has numerous advantages including cost savings and improved patient
      satisfaction. The aim of this study is to evaluate the safety of SDD among
      patients treated with OA in a real-world setting. METHODS: This was a single
      center retrospective analysis of patients undergoing OA. In-hospital and 30-day
      outcomes were assessed for major adverse cardiac events (MACE), device-related
      events and hospital readmissions. RESULTS: There were 309 patients treated with
      OA of whom 94 had SDD (30.4%). Among SDD patients, there were no acute procedural
      complications and all patients were safely discharged on the day of the
      procedure. MACE at 30 days occurred in 1 patient (1.06%) due to major bleeding in
      the setting of a gastric arteriovenous malformation. There were 8 patients with
      unplanned 30-day readmissions (8.5%). CONCLUSION: SDD after OA in patients with
      heavily calcified lesions appears to be safe, with low rates of adverse events
      and readmissions in select patients. In patients with SDD treated with OA,
      unplanned readmission occurred at a similar rate to the statewide average 30-day
      PCI readmission rate. Larger studies are needed to confirm the safety of this
      treatment paradigm and the potential cost savings.

PMID- 30224314
TI  - Is bromelain an effective drug for the control of pain and inflammation
      associated with impacted third molar surgery? Systematic review and meta
      analysis.
AB  - The aim of this systematic review was to determine whether bromelain is an
      effective drug for the control of pain and inflammation associated with third
      molar surgery. Randomized, controlled clinical trials on the subject were
      identified through a systematic search of the literature using the
      PubMed/MEDLINE, Scopus, and Cochrane Library databases. This review was conducted
      in accordance with the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA). Two independent, blinded reviewers selected studies based on
      the inclusion criteria. Divergences of opinion were resolved by consensus. A meta
      analysis was performed for the outcomes pain and trismus and was based on the
      inverse variance method for continuous outcomes, considering the mean difference
      (MD) and corresponding 95% confidence interval (CI). A total of 186 articles were
      initially retrieved from the databases. After the different stages of the
      selection process, five articles reporting data for a total 252 patients remained
      and were included in the review. Bromelain proved to be effective at controlling
      postoperative pain at 48-72h after surgery (P=0.03; MD -0.89, 95% CI -1.70 to 
      0.09), but did not achieve a significant effect in comparison to the control
      group with regard to oedema or trismus.

PMID- 30224313
TI  - Radiomics signature of computed tomography imaging for prediction of survival and
      chemotherapeutic benefits in gastric cancer.
AB  - To develop and validate a radiomics signature for the prediction of gastric
      cancer (GC) survival and chemotherapeutic benefits. In this multicenter
      retrospective analysis, we analyzed the radiomics features of portal venous-phase
      computed tomography in 1591 consecutive patients. A radiomics signature was
      generated by using the Lasso-Cox regression model in 228 patients and validated
      in internal and external validation cohorts. Radiomics nomograms integrating the
      radiomics signature were constructed, demonstrating the incremental value of the
      radiomics signature to the traditional staging system for individualized survival
      estimation. The performance of the nomograms was assessed with respect to
      calibration, discrimination, and clinical usefulness. The radiomics signature
      consisted of 19 selected features and was significantly associated with DFS
      (disease-free survival) and OS (overall survival). Multivariate analysis
      demonstrated that the radiomics signature was an independent prognostic factor.
      Incorporating the radiomics signature into the radiomics-based nomograms resulted
      in better performance for the estimation of DFS and OS than the
      clinicopathological nomograms and TNM staging system, with improved accuracy of
      the classification of survival outcomes. Further analysis showed that stage II
      and III patients with higher radiomics scores exhibited a favorable response to
      chemotherapy. In conclusion, the newly developed radiomics signature is a
      powerful predictor of DFS and OS, and it may predict which patients with stage II
      and III GC benefit from chemotherapy.

PMID- 30224315
TI  - Long-term outcomes of combined endoscopic resection and chemoradiotherapy for
      esophageal squamous cell carcinoma with submucosal invasion. Author's reply.

PMID- 30224312
TI  - Small-molecule PROTACs: An emerging and promising approach for the development of
      targeted therapy drugs.
AB  - There are several challenges towards the development and clinical use of small
      molecule inhibitors, which are currently the main type of targeted therapies
      towards intracellular proteins. PROteolysis-TArgeting Chimeras (PROTACs) exploit
      the intracellular ubiquitin-proteasome system to selectively degrade target
      proteins. Recently, small-molecule PROTACs with high potency have been frequently
      reported. In this review, we summarize the emerging characteristics of small
      molecule PROTACs, such as inducing a rapid, profound and sustained degradation,
      inducing a robust inhibition of downstream signals, displaying enhanced target
      selectivity, and overcoming resistance to small molecule inhibitors. In tumor
      xenografts, small-molecule PROTACs can significantly attenuate tumor progression.
      In addition, we also introduce recent developments of the PROTAC technology such
      as homo-PROTACs. The outstanding advantages over traditional small-molecule drugs
      and the promising preclinical data suggest that small-molecule PROTAC technology
      has the potential to greatly promote the development of targeted therapy drugs.

PMID- 30224316
TI  - Association of non-alcoholic fatty liver disease with thyroid function: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common
      chronic liver diseases. The relationship of NAFLD with thyroid function
      parameters and hypothyroidism remains controversial. AIM: To clarify the effect
      of thyroid function parameters and hypothyroidism on the development of NAFLD and
      progression to nonalcoholic steatohepatitis (NASH). METHODS: PubMed, EMBASE, and
      Cochrane library databases were searched. Study quality was assessed. Weighted
      mean difference (WMD) and odds ratio (OR) with 95% confidence interval (CI) were
      calculated. RESULTS: Twenty six studies involving 61,548 participants were
      eligible, most of which were of high quality. NAFLD/NASH patients had
      significantly higher TSH levels than controls in adults (NAFLD versus health: WMD
      = 0.105, 95%CI = 0.012-0.197; NAFLD versus euthyroidism: WMD = 0.100, 95%CI =
      0.005-0.194; NASH versus NAFLD: WMD = 0.540, 95%CI = 0.136-0.944) and
      children/adolescents (NAFLD versus lean controls: WMD = 1.039, 95%CI = 0.104
      1.973; NAFLD versus overweight/obese controls: WMD = 0.485, 95%CI = 0.267-.703).
      Unclassified hypothyroidism was positively associated with the risk of NAFLD/NASH
      in adults (NAFLD versus health: OR = 1.605, 95%CI = 1.180-2.183; NASH versus
      NAFLD: OR = 2.317, 95%CI = 1.425-3.768) and children/adolescents (NAFLD versus
      overweight/obese controls: OR = 2.015, 95%CI = 1.246-3.258). However, the
      statistical results were inconsistent among the subgroup meta-analyses of
      subclinical and overt hypothyroidism. Association of NAFLD with FT3 and FT4
      levels was heterogeneous among population. CONCLUSION: TSH level may be an
      important risk factor for the development and progression of NAFLD, independent
      of thyroid hormones.

PMID- 30224317
TI  - Chronic use of statins and risk of post-ERCP acute pancreatitis (STARK): Study
      protocol for an international multicenter prospective cohort study.
AB  - BACKGROUND: Acute pancreatitis (AP) is the most common complication after
      endoscopic retrograde cholangiopancreatography (ERCP). Statins have been
      traditionally associated to an increased risk of AP, however, recent evidence
      suggests that statins may have a protective role against this disease. AIMS: Our
      primary aim is to investigate whether the use of statins has a protective effect
      against post-ERCP pancreatitis (PEP). Secondary outcomes are: to evaluate the
      effect of other drugs on the incidence of PEP; to ascertain the relationship
      between the use of statins and the severity of PEP; and to evaluate the effect of
      other risk and protective factors on the incidence of PEP. METHODS: STARK is an
      international multicenter prospective cohort study. Centers from Spain, Italy,
      Croatia, Finland and Sweden joined this study. The total sample size will include
      about 1016 patients, which was based on assuming a 5% incidence of PEP among non
      statin (NSt) users, a 1-3 ratio of statin (St) and NSt consumers respectively, a
      70% decrease in PEP among St consumers, an alpha-error of 0.05 and beta-error of
      0.20. All patients aged >=18 years scheduled for ERCP will be offered to enter
      the study. DISCUSSION: STARK study will ascertain whether statins, a safe, widely
      used and inexpensive drug, can modify the incidence of PEP.

PMID- 30224318
TI  - Long-term safety and tolerability of nintedanib in patients with idiopathic
      pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON.
AB  - BACKGROUND: The efficacy and safety of nintedanib, an intracellular tyrosine
      kinase inhibitor, in patients with idiopathic pulmonary fibrosis were assessed in
      two phase 3, placebo-controlled INPULSIS trials. Patients who completed the 52
      week treatment period in an INPULSIS trial could receive open-label nintedanib in
      the extension trial, INPULSIS-ON. We aimed to assess the long-term efficacy and
      safety of nintedanib in INPULSIS-ON. METHODS: Patients who completed the 52-week
      treatment period of INPULSIS, and the follow-up visit 4 weeks later, were
      eligible for INPULSIS-ON. The off-treatment period between INPULSIS and INPULSIS
      ON could be 4-12 weeks. Patients receiving nintedanib 150 mg twice daily or
      placebo at the end of an INPULSIS trial received nintedanib 150 mg twice daily in
      INPULSIS-ON. Patients receiving nintedanib 100 mg twice daily or placebo at the
      end of an INPULSIS trial could receive nintedanib 100 mg twice daily or 150 mg
      twice daily in INPULSIS-ON. Spirometric tests were done at baseline, at weeks 2,
      4, 6, 12, 24, 36, 48, and then every 16 weeks. The primary outcome of INPULSIS-ON
      was to characterise the long-term safety and tolerability of nintedanib in
      patients with idiopathic pulmonary fibrosis, and this was analysed in patients
      who received at least one dose of nintedanib in INPULSIS-ON. This study is
      registered with ClinicalTrials.gov, number NCT01619085, and with EudraCT, number
      2011-002766-21. FINDINGS: The first patient was enrolled into INPULSIS-ON in July
      2, 2012. Of 807 patients who completed the INPULSIS trials, 734 (91%) were
      treated in INPULSIS-ON. 430 (59%) patients had received nintedanib in INPULSIS
      and continued nintedanib in INPULSIS-ON, and 304 (41%) had received placebo in
      INPULSIS and initiated nintedanib in INPULSIS-ON. Median exposure time for
      patients treated with nintedanib in both the INPULSIS and INPULSIS-ON trials was
      44.7 months (range 11.9-68.3). The safety profile of nintedanib in INPULSIS-ON
      was consistent with that observed in INPULSIS. Diarrhoea was the most frequent
      adverse event in INPULSIS-ON (60.1 events per 100 patient exposure-years in
      patients who continued nintedanib, 71.2 events per 100 patient exposure-years in
      patients who initiated nintedanib). 20 (5%) of 430 patients who continued
      nintedanib and 31 (10%) of 304 patients who initiated nintedanib permanently
      discontinued nintedanib because of diarrhoea. The adverse event that most
      frequently led to permanent discontinuation of nintedanib was progression of
      idiopathic pulmonary fibrosis (51 [12%] patients continuing nintedanib and 43
      [14%] patients initiating nintedanib). The event rate of bleeding was 8.4 events
      per 100 patient exposure-years in patients who continued nintedanib and 6.7
      events per 100 patient exposure-years in patients who initiated nintedanib. The
      event rate of major adverse cardiovascular events was 3.6 events per 100 patient
      exposure-years in patients who continued nintedanib and 2.4 events per 100
      patient exposure-years in patients who initiated nintedanib. The event rate of
      myocardial infarction using the broad scope (ie, all possible cases) was 1.3
      events per 100 patient exposure-years in patients who continued nintedanib and
      0.7 events per 100 patient exposure-years in patients who initiated nintedanib.
      INTERPRETATION: These findings suggest that nintedanib has a manageable safety
      and tolerability profile over long-term use, with no new safety signals. Patients
      with idiopathic pulmonary fibrosis could use nintedanib over the long-term to
      slow disease progression. FUNDING: Boehringer Ingelheim.

PMID- 30224320
TI  - Roflumilast for eosinophilic chronic obstructive pulmonary disease?

PMID- 30224319
TI  - Anti-inflammatory effects of roflumilast in chronic obstructive pulmonary disease
      (ROBERT): a 16-week, randomised, placebo-controlled trial.
AB  - BACKGROUND: The clinical effects of roflumilast, a selective phosphodiesterase-4
      inhibitor, are well established, but little is known about the anti-inflammatory
      mechanisms underlying the drug's efficacy. The aim of the ROflumilast Biopsy
      European Research Trial (ROBERT) was to assess the anti-inflammatory effects of
      roflumilast on bronchial mucosal inflammation in patients with moderate-to-severe
      chronic obstructive pulmonary disease (COPD) and chronic bronchitis. METHODS:
      ROBERT was a randomised, double-blind, placebo-controlled trial done at 18 sites
      in five countries. Eligible patients were aged 40-80 years, had COPD, and had had
      a chronic productive cough for 3 months in each of the two previous years.
      Patients also had to have a post-bronchodilator predicted FEV1 30-80% and a post
      bronchodilator FEV1/forced vital capacity ratio of 70% or less. Patients entered
      a 6-week run-in period before being randomly assigned (1:1) via a computerised
      central randomisation system to roflumilast 500 MUg once daily or placebo for 16
      weeks, in addition to bronchodilator therapy (inhaled corticosteroids were not
      permitted). Randomisation was stratified by concomitant use of long-acting beta
      agonist. Both participants and investigators were masked to group assignment.
      Roflumilast and placebo were supplied as identical yellow, triangular tablets.
      Airway inflammation was assessed by quantification of inflammatory cells in
      bronchial biopsy samples and induced sputum samples. The primary endpoint was the
      change in the number of CD8 inflammatory cells in bronchial biopsy submucosa from
      randomisation to week 16 in the intention-to-treat population. Changes in cell
      counts of additional inflammatory markers, including eosinophils, were assessed
      as secondary endpoints. This trial is registered with ClinicalTrials.gov, number
      NCT01509677, and is closed to new participants, with follow-up completed.
      FINDINGS: Between Jan 4, 2012, and Feb 11, 2016, 158 patients were randomly
      assigned: 79 to the roflumilast group, and 79 to the placebo group. At week 16,
      the change in the number of CD8 cells in the bronchial submucosa did not differ
      significantly between the roflumilast and placebo groups (treatment ratio 1.03
      [95% CI 0.82-1.30]; p=0.79). However, compared with placebo, roflumilast was
      associated with a significant reduction in eosinophils in bronchial biopsy
      samples at week 16 (treatment ratio 0.53 [95% CI 0.34-0.82]; p=0.0046).
      Significant reductions in both absolute (p=0.0042) and differential (p=0.0086)
      eosinophil cell counts in induced sputum were also noted with roflumilast
      compared with placebo, but peripheral blood eosinophil counts were not
      significantly affected. We noted no other significant effects of roflumilast on
      bronchial mucosal inflammatory cells. The most common (ie, occurring in >5%
      patients) moderate adverse events were worsening of COPD (three [4%] patients in
      the roflumilast group vs seven [9%] in the placebo group), cough (six [8%] vs
      four [5%]), diarrhoea (four [5%] vs three [4%]), and nasopharyngitis (three [4%]
      vs five [6%]). Severe adverse events included worsening of COPD, which occurred
      in four (5%) patients in the roflumilast group and two (3%) in the placebo group.
      No deaths occurred during the study. Serious adverse events occurred in eight
      (10%) patients in the roflumilast group and five (6%) in the placebo group.
      INTERPRETATION: 16 weeks of treatment with roflumilast did not affect the number
      of CD8 cells in bronchial submucosa compared with placebo. However, we noted
      significant reductions in eosinophil cell counts in bronchial biopsy samples and
      induced sputum, generating the hypothesis that the effect of roflumilast in COPD
      could be mediated by an effect on lung eosinophils. FUNDING: Takeda and
      AstraZeneca.

PMID- 30224321
TI  - IPF diagnosis: flexibility is a virtue.

PMID- 30224323
TI  - Time to focus on paediatric critical care survivorship.

PMID- 30224324
TI  - Efficacy data in treatment extension studies of idiopathic pulmonary fibrosis:
      interpret with caution.

PMID- 30224327
TI  - Tuberculosis incidence in England hits 30-year low.

PMID- 30224326
TI  - Neuromuscular blocking agents and postoperative pulmonary complications.

PMID- 30224325
TI  - Long-term developmental effects of withholding parenteral nutrition for 1 week in
      the paediatric intensive care unit: a 2-year follow-up of the PEPaNIC
      international, randomised, controlled trial.
AB  - BACKGROUND: The paediatric early versus late parenteral nutrition in critical
      illness (PEPaNIC) multicentre, randomised, controlled trial showed that, compared
      with early parenteral nutrition, withholding supplemental parenteral nutrition
      for 1 week in the paediatric intensive care unit (PICU; late parenteral
      nutrition) reduced infections and accelerated recovery from critical illness in
      children. We aimed to investigate the long-term impact on physical and
      neurocognitive development of early versus late parenteral nutrition. METHODS: In
      this preplanned 2-year follow-up study, all patients included in the PEPaNIC
      trial (which was done in University Hospitals Leuven, Belgium; Erasmus Medical
      Centre-Sophia Children's Hospital, Rotterdam, Netherlands; and Stollery
      Children's Hospital, Edmonton, AB, Canada) were approached for possible
      assessment of physical and neurocognitive development compared with healthy
      children who were matched for age and sex, and who had never been admitted to a
      neonatal ICU or a PICU. Assessed outcomes comprised anthropometric data; health
      status; parent-reported or caregiver-reported executive functions and emotional
      and behavioural problems; and tests for intelligence, visual-motor integration,
      alertness, motor coordination, inhibitory control, cognitive flexibility, and
      memory. To address partial responses among the children tested, we did multiple
      data imputation by chained equations before univariable and multivariable linear
      and logistic regression analyses adjusted for risk factors. This trial is
      registered with ClinicalTrials.gov, number NCT01536275. FINDINGS: At the 2-year
      follow-up, 60 (8%) of 717 children who received late parenteral nutrition and 63
      (9%) of 723 children who received early parenteral nutrition had died (p=0.81).
      68 (9%) of 717 children who received late and 91 (13%) of 723 children who
      received early parenteral nutrition were too disabled for neurocognitive
      assessment (p=0.059), and 786 patients (395 assigned to late and 391 assigned to
      early parenteral nutrition) consented for testing. 786 patients and 405 healthy
      control children underwent long-term outcome testing between Aug 4, 2014, and Jan
      19, 2018, and were included in the imputation model for subsequent multivariable
      analyses. Late parenteral nutrition did not adversely affect anthropometric data,
      health status, or neurological functioning, and improved parent-reported or
      caregiver-reported executive functioning (late vs early parenteral nutrition beta
      estimate -2.258, 95% CI -4.012 to -0.504; p=0.011), more specifically inhibition
      (-3.422, -5.171 to -1.673; p=0.0001), working memory (-2.016, -3.761 to -0.270;
      p=0.023), and meta-cognition (-1.957, -3.694 to -0.220; p=0.027). Externalising
      behavioural problems (beta estimate -1.715, 95% CI -3.325 to -0.106; p=0.036) and
      visual-motor integration (0.468, 0.087 to 0.850; p=0.016) were also improved in
      the late parenteral nutrition group compared with the early parenteral nutrition
      group. After Bonferroni correction for multiple comparisons, the effect on
      inhibitory control remained significant (p=0.0001). INTERPRETATION: Withholding
      early parenteral nutrition for 1 week in the PICU did not negatively affect
      survival, anthropometrics, health status, and neurocognitive development, and
      improved inhibitory control 2 years after PICU admission. FUNDING: European
      Research Council Advanced Grant, Methusalem programme provided by the Flemish
      Government, Flemish Agency for Innovation by Science and Technology (IWT),
      Research Foundation Flanders (FWO), Sophia Children's Hospital Foundation (SSWO),
      Stichting Agis Zorginnovatie, Erasmus Trustfonds, and European Society for
      Parenteral and Enteral Nutrition (ESPEN) research grant.

PMID- 30224328
TI  - Elevated vWF Antigen Serum Levels Are Associated With Poor Prognosis, and
      Decreased Circulating ADAMTS-13 Antigen Levels Are Associated With Increased IgM
      Levels and Features of WM but not Increased vWF Levels in Patients With
      Symptomatic WM.
AB  - BACKGROUND: Waldenstrom's macroglobulinemia (WM) is a rare malignancy
      characterized by bone marrow infiltration by lymphoplasmacytic cells and the
      presence of a monoclonal IgM paraprotein. The interactions of lymphoplasmacytic
      cells with other cells in their microenvironment, including mast cells and
      endothelial cells, support their survival and proliferation and can induce
      resistance to therapy. von Willebrand factor (vWF) plays a key role in primary
      hemostasis but is also a marker of endothelial "stimulation." High levels of vWF
      have been associated with an adverse prognosis in patients with symptomatic WM
      and might reflect the interactions between lymphoplasmacytic cells and other
      cells of their microenvironment. MATERIALS AND METHODS: Considering vWF and
      ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1
      motif, member 13) as markers of endothelial dysfunction and activation, we
      evaluated the prognostic importance of vWF and ADAMTS-13 antigen levels in the
      serum of patients with previously untreated symptomatic WM to validate vWF as a
      possible prognostic marker for progression-free and overall survival. We also
      validated the measurement of vWF in the serum instead of citrated plasma and
      investigated the possible correlations of ADAMTS-13 antigen levels with disease
      characteristics. The analysis included 42 patients with symptomatic WM and 19
      matched healthy controls. RESULTS: The serum levels of vWF antigen provided
      significant prognostic information, and patients with levels >= 200 IU/dL had a
      very poor prognosis compared with patients with lower levels. The ADAMTS-13
      antigen levels were decreased in WM patients and correlated with the IgM levels,
      beta2-microglobulin, and extent of bone marrow infiltration. CONCLUSION: vWF
      levels measured in the serum could become an important prognostic marker in
      patients with WM and requires further investigation.

PMID- 30224329
TI  - Influence of Gender and Age on the Willingness to Reduce Nicotine Consumption
      Results of a Survey in Urological Cancer Patients (KRAUT Study).
AB  - PURPOSE: Our objective was to investigate whether patients with urologic tumors
      were aware of smoking as a risk factor for the development and progression of
      several urologic cancers and the extent of the medical education they had
      received. Another aim was to investigate whether gender or age influenced
      patients' willingness to change their smoking habits. MATERIALS AND METHODS:
      Patients with histologically malignant urologic tumors were enrolled in our
      questionnaire-based study from September 2013 to December 2014 in 2 urology
      departments. Patients were asked about their smoking habits and their general
      understanding of the relationship between smoking and the onset of cancer
      (urologic cancer and lung cancer). Also, the extent of information they had
      acquired from a physician was assessed. The descriptive and oncologic data of the
      patients were recorded. RESULTS: Of 258 enrolled patients, 186 (72.1%) had never
      had an informational discussion with a doctor about smoking and their urologic
      tumor disease. Of the 160 active and former smokers, only 45 (28.1%) were
      planning to stop or reduce smoking because of their tumor disease. The
      willingness to change smoking habits was greater for women, with a statistically
      significant difference (odds ratio, 5.59; P = .002). Younger patients aged <58
      years were also more willing to reduce or stop smoking. CONCLUSION: In our study,
      most patients with urologic cancer were unaware of smoking as the most probable
      cause of tumor development. The patients had not received proper counseling from
      doctors on smoking and the risk it poses for tumor progression. Efforts to
      balance compliance among the genders and age groups through risk-adapted
      counseling should be undertaken.

PMID- 30224331
TI  - Successful Lung Re-transplant in a Patient with Cepacia Syndrome due to
      Burkholderia ambifaria.
AB  - Chronic airway inflammation and infection drive morbidity and mortality among
      patients with cystic fibrosis (CF). While Haemophilus influenzae and
      Staphylococcus aureus predominate in children, the prevalence of Pseudomonas
      aeruginosa increases as patients age. Other bacteria, including species within
      the Burkholderia cepacia complex (Bcc), are also more prevalent among adults with
      CF. Species within the Bcc accelerate lung function decline and can trigger
      development of "cepacia syndrome," both before and after lung transplantation. As
      a result, some centers advise against lung transplantation for Bcc-infected
      patients; however, little is known about the relative virulence of uncommon Bcc
      species. We describe a successful lung re-transplant in a patient with CF,
      chronic Burkholderia ambifaria airway infection, and cepacia syndrome.

PMID- 30224330
TI  - Clinical Outcomes in Patients With Metastatic Papillary Renal-Cell Carcinoma: A
      Multi-Institutional Study in Japan.
AB  - BACKGROUND: Standard treatments have not been established in metastatic papillary
      renal-cell carcinoma (PRCC). We aimed to investigate treatment outcomes in
      patients with mPRCC. PATIENTS AND METHODS: This study included 51 patients who
      were diagnosed with PRCC at 14 institutions. Pathologic slides were reviewed by
      pathologists. The associations between clinical factors and overall survival (OS)
      were analyzed. RESULTS: Final pathologic diagnoses could be determined in 50
      patients. Thirty-five tumors were diagnosed as PRCC (type 2 PRCC, 91.4%), and 15
      were diagnosed as other histologic types. Targeted therapies (TTs) were provided
      to 25 mPRCC patients. Patients treated with TT survived significantly longer than
      those treated before the era of TT (median OS, 22.5 vs. 6.3 months; P = .0035).
      Median OS of patients who experienced stable disease for >= 9 months using single
      TT was 43.1 months. Patients treated with a tyrosine kinase inhibitor (TKI) as
      first-line TT survived longer after TT initiation than those treated with an mTOR
      inhibitor (median, 22.4 vs. 11.7 months; P = .2684). Patients treated with TKIs
      in both first- and second-line settings had significantly better survival after
      TT initiation than those treated with a TKI in one therapy line and an mTOR
      inhibitor in the other (31.4 vs. 12.9 months, P = .0172). Patients treated with a
      TKI as second-line TT survived significantly longer after second-line TT
      initiation than did those treated with an mTOR inhibitor (16.2 vs. 7.4 months, P
      = .0016). CONCLUSION: Prognoses of patients with mPRCC were improved by TT, and
      TKIs appeared to be the treatment of choice in both the first- and second-line
      settings.

PMID- 30224332
TI  - Repeated hot water and steam disinfection of Pari LC Plus(r) nebulizers alter
      nebulizer output.
AB  - Currently, cystic fibrosis patients require daily nebulized treatments to achieve
      optimal lung health. Growth of pathogenic bacteria in patient nebulizers is well
      known, and disinfection guidelines have been established. In this short
      communication, we sought to discover what effect, if any, repeated
      nebulization/disinfection cycles had on nebulizer output. We nebulized saline
      repeatedly after exposure to boiling water, steam, and alcohol disinfection
      methods. While alcohol disinfection did not affect nebulizer output, boiling
      water and steam significantly decreased nebulizer output from baseline, 74.1 +/-
      5.9% (p = 0.022) and steam 63.6 +/- 6.5% (p = 0.0048) after 60 cycles
      respectively. This decrease in nebulizer output could significantly increase the
      duration of nebulizer treatment time and negatively impact the burden of care on
      patients with cystic fibrosis.

PMID- 30224333
TI  - An mHealth App for Self-Management of Chronic Lower Back Pain (Limbr): Pilot
      Study.
AB  - BACKGROUND: Although mobile health (mHealth) interventions can help improve
      outcomes among patients with chronic lower back pain (CLBP), many available
      mHealth apps offer content that is not evidence based. Limbr was designed to
      enhance self-management of CLBP by packaging self-directed rehabilitation
      tutorial videos, visual self-report tools, remote health coach support, and
      activity tracking into a suite of mobile phone apps, including Your Activities of
      Daily Living, an image-based tool for quantifying pain-related disability.
      OBJECTIVE: The aim is to (1) describe patient engagement with the Limbr program,
      (2) describe patient-perceived utility of the Limbr program, and (3) assess the
      validity of the Your Activities of Daily Living module for quantifying functional
      status among patients with CLBP. METHODS: This was a single-arm trial utilizing a
      convenience sample of 93 adult patients with discogenic back pain who visited a
      single physiatrist from January 2016 to February 2017. Eligible patients were
      enrolled in 3-month physical therapy program and received the Limbr mobile phone
      app suite for iOS or Android. The program included three daily visual self
      reports to assess pain, activity level, and medication/coping mechanisms;
      rehabilitation video tutorials; passive activity-level measurement; and chat
      based health coaching. Patient characteristics, patient engagement, and perceived
      utility were analyzed descriptively. Associations between participant
      characteristics and program interaction were analyzed using multiple linear
      regression. Associations between Your Activities of Daily Living and Oswestry
      Disability Index (ODI) assessments were examined using Pearson correlation and
      hierarchical linear modeling. RESULTS: A total of 93 participants were enrolled;
      of these, 35 (38%) completed the program (age: mean 46, SD 16 years; female:
      22/35, 63%). More than half of completers finished assessments at least every 3
      days and 70% (19/27) used the rehabilitation component at least once a week.
      Among respondents to a Web-based feedback survey, 76% (16/21) found the daily
      notifications helped them remember to complete their exercises, 81% (17/21) found
      the system easy to use, and 62% (13/21) rated their overall experience good or
      excellent. Baseline Your Activities of Daily Living score was a significant
      predictor of baseline ODI score, with ODI increasing by 0.30 units for every 1
      unit increase in Your Activities of Daily Living (P<.001). Similarly,
      hierarchical linear modeling analysis indicated that Your Activities of Daily
      Living daily assessment scores were significant predictors of ODI scores over the
      course of the study (P=.01). CONCLUSIONS: Engagement among participants who
      completed the Limbr program was high, and program utility was rated positively by
      most respondents. Your Activities of Daily Living was significantly associated
      with ODI scores, supporting the validity of this novel tool. Future studies
      should assess the effect of Limbr on clinical outcomes, evaluate its use among a
      wider patient sample, and explore strategies for reducing attrition. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT03040310;
      https://clinicaltrials.gov/ct2/show/NCT03040310 (Archived by WebCite at
      http://www.webcitation.org/722mEvAiv).

PMID- 30224334
TI  - Use and the Users of a Patient Portal: Cross-Sectional Study.
AB  - BACKGROUND: Patient portals offer patients access to their medical information
      and tools to communicate with health care providers. It has been shown that
      patient portals have the potential to positively impact health outcomes and
      efficiency of health care. It is therefore important that health care
      organizations identify the patients who use or do not use the patient portal and
      explore the reasons in either case. The Unified Theory of Acceptance and Use of
      Technology (UTAUT) is a frequently used theory for explaining the use of
      information technology. It consists of the following constructs: performance
      expectancy, effort expectancy, social influence, facilitating conditions, and
      behavioral intention to use. OBJECTIVE: This study aimed to explore the
      prevalence of patient portal use and the characteristics of patients who use or
      do not use a patient portal. The main constructs of UTAUT, together with
      demographics and disease- and care-related characteristics, have been measured to
      explore the predictive factors of portal use. METHODS: A cross-sectional study
      was conducted in the outpatient departments for adult patients of a university
      hospital in the Netherlands. Following outcomes were included: self-reported
      portal use, characteristics of users such as demographics, disease- and care
      related data, eHealth literacy (modified score), and scores of UTAUT constructs.
      Descriptive analyses and univariate and multivariate logistic regression were
      also conducted. RESULTS: In the analysis, 439 adult patients were included.
      Furthermore, 32.1% (141/439) identified as being a user of the patient portal;
      31.2% (137/439) indicated as nonusers, but being aware of the existence of the
      portal; and 36.6% (161/439) as being nonusers not aware of the existence of the
      portal. In the entire study population, the factors of being chronically ill
      (odds ratio, OR 1.62, 95% CI 1.04-2.52) and eHealth literacy (modified score; OR
      1.12, 95% CI 1.07-1.18) best predicted portal use. In users and nonusers who were
      aware of the portal, UTAUT constructs were added to the multivariate logistic
      regression, with chronically ill and modified eHealth literacy sum score. Effort
      expectancy (OR 13.02, 95% CI 5.68-29.87) and performance expectancy (OR 2.84, 95%
      CI 1.65-4.90) are shown to significantly influence portal use in this group.
      CONCLUSIONS: Approximately one-third of the patients of a university hospital
      self-reported using the patient portal; most expressed satisfaction. At first
      sight, being chronically ill and higher scores on the modified eHealth literacy
      scale explained portal use. Adding UTAUT constructs to the model revealed that
      effort expectancy (ease of use and knowledge and skills related to portal use)
      and performance expectancy (perceived usefulness) influenced portal use.
      Interventions to improve awareness of the portal and eHealth literacy skills of
      patients and further integration of the patient portal in usual face-to-face care
      are needed to increase use and potential subsequent patient benefits.

PMID- 30224335
TI  - Text Messaging Interventions for Improvement in Physical Activity and Sedentary
      Behavior in Youth: Systematic Review.
AB  - BACKGROUND: The use of text messages (short message service, SMS) to change
      physical activity and sedentary behavior in youth is of interest due to the need
      for novel, more effective intervention approaches. Previous reviews have examined
      a variety of technology-based interventions and their impact on different health
      behaviors, but evidence regarding the impact of just SMS on physical activity and
      sedentary behavior is lacking. OBJECTIVE: The aim of this study was to assess the
      effectiveness and use of theory of SMS interventions for improving physical
      activity and sedentary behavior in youth. METHODS: Authors systematically
      searched electronic databases from March to November 2017. Citations were sifted
      using additional reviewers, and a qualitative synthesis of eligible studies was
      conducted using piloted data extraction forms. To be eligible for inclusion,
      studies had to be of a randomized controlled or quasi-experimental design,
      incorporate SMS, involve adolescents between the ages of 10 and 19 years, and
      assess at least one physical activity or sedentary behavior outcome. Risk of bias
      was assessed using the Cochrane Collaboration's Risk of Bias tool. RESULTS: A
      total of 13 studies reporting 11 interventions were included in the qualitative
      analysis. Studies included interventions that were conducted in schools, online,
      or face-to-face. Studies were of high heterogeneity with regard to study
      duration, participant characteristics, intervention content, and outcome
      measures. Findings were equivocal with regard to intervention effectiveness for
      physical activity and sedentary behavior. Overall, 7 interventions resulted in an
      improvement for physical activity and 6 for sedentary behavior. All studies were
      judged to be of high risk of bias for at least 1 item. CONCLUSIONS: Some studies
      in this review showed promising results for using SMS to improve physical
      activity and sedentary behavior in youth. High heterogeneity of design and
      outcome measures precluded data pooling and conclusions as to which specific
      intervention elements are linked to increased effectiveness cannot be drawn. The
      authors propose incorporating the following elements in future studies: specific
      focus on desired health behavior; mixed-methods design; include long-term follow
      up; include self-monitoring, goal setting, and feedback; combine SMS with a
      mobile app; and send 3 or more SMS text messages per week. More rigorous studies
      are needed to explore the relationship between intervention effectiveness and
      specific intervention components such as content and delivery.

PMID- 30224336
TI  - An Efficient Genome Editing Strategy To Generate Putative Null Mutants in
      Caenorhabditis elegans Using CRISPR/Cas9.
AB  - Null mutants are essential for analyzing gene function. Here, we describe a
      simple and efficient method to generate Caenorhabditis elegans null mutants using
      CRISPR/Cas9 and short single stranded DNA oligo repair templates to insert a
      universal 43-nucleotide-long knock-in cassette (STOP-IN) into the early exons of
      target genes. This STOP-IN cassette has stop codons in all three reading frames
      and leads to frameshifts, which will generate putative null mutations regardless
      of the reading frame of the insertion position in exons. The STOP-IN cassette
      also contains an exogenous Cas9 target site that allows further genome editing
      and provides a unique sequence that simplifies the identification of successful
      insertion events via PCR. As a proof of concept, we inserted the STOP-IN cassette
      at a Cas9 target site in aex-2 to generate new putative null alleles by injecting
      preassembled Cas9 ribonucleoprotein and a short synthetic single stranded DNA
      repair template containing the STOP-IN cassette and two ~35-nucleotide-long
      homology arms identical to the sequences flanking the Cas9 cut site. We showed
      that these new aex-2 alleles phenocopied an existing loss-of-function allele of
      aex-2 We further showed that the new aex-2 null alleles could be reverted back to
      the wild-type sequence by targeting the exogenous Cas9 cut site included in the
      STOP-IN cassette and providing a single stranded wild-type DNA repair oligo. We
      applied our STOP-IN method to generate new putative null mutants for 20
      additional genes, including three pharyngeal muscle-specific genes (clik-1, clik
      2, and clik-3), and reported a high insertion rate (46%) based on the animals we
      screened. We showed that null mutations of clik-2 cause recessive lethality with
      a severe pumping defect and clik-3 null mutants have a mild pumping defect, while
      clik-1 is dispensable for pumping. We expect that the knock-in method using the
      STOP-IN cassette will facilitate the generation of new null mutants to understand
      gene function in C. elegans and other genetic model organisms.

PMID- 30224338
TI  - To Cycle or Fight-CDK4/6 Inhibitors at the Crossroads of Anticancer Immunity.
AB  - Dysregulation of cell division resulting in aberrant cell proliferation is a key
      hallmark of cancer, making it a rational and important target for innovative
      anticancer drug development. Three selective cyclin-dependent kinases 4 and 6
      (CDK4/6) inhibitors are FDA and European Medicines Agency (EMA) approved for
      hormone receptor-positive/HER2-negative advanced breast cancer. A major emerging
      appreciation is that these inhibitors not only are cytostatic, but also play
      critical roles in the interaction between tumor cells and the host immune
      response. However, to trigger an effective immune response, lymphocytes must also
      proliferate. This review aims to assimilate our emerging understanding on the
      role of CDK4/6 inhibitors in cell-cycle control, as well as their biological
      effect on T cells and other key immune cells, and the confluence of preclinical
      evidence of augmentation of anticancer immunity by these drugs. We aim to provide
      a framework for understanding the role of the cell cycle in anticancer immunity,
      discussing ongoing clinical trials evaluating this concept and challenges for
      developing rational combinations with immunotherapy. Clin Cancer Res; 1-8.
      (c)2018 AACR.

PMID- 30224337
TI  - USP7 cooperates with NOTCH1 to drive the oncogenic transcriptional program in T
      cell leukemia.
AB  - PURPOSE: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease,
      affecting children and adults. Chemotherapy treatments show high response rates
      but have debilitating effects and carry risk of relapse. Previous work implicated
      NOTCH1 and other oncogenes. However, direct inhibition of these pathways affects
      healthy tissues and cancer alike. Our goal in this work has been to identify
      enzymes active in T-ALL whose activity could be targeted for therapeutic
      purposes. EXPERIMENTAL DESIGN: To identify and characterize new NOTCH1 druggable
      partners in T-ALL, we coupled studies of the NOTCH1 interactome to expression
      analysis and a series of functional analyses in cell lines, patient samples and
      xenograft models. RESULTS: We demonstrate that ubiquitin-specific protease 7
      (USP7) interacts with NOTCH1 and controls leukemia growth by stabilizing the
      levels of NOTCH1 and JMJD3 histone demethylase. USP7 is highly expressed in T-ALL
      and is transcriptionally regulated by NOTCH1. In turn, USP7 controls NOTCH1
      levels through deubiquitination. USP7 binds oncogenic targets and controls gene
      expression through stabilization of NOTCH1 and JMJD3 and ultimately H3K27me3
      changes. We also show that USP7 and NOTCH1 bind T-ALL superenhancers, and
      inhibition of USP7 leads to a decrease of the transcriptional levels of NOTCH1
      targets and significantly blocks T-ALL cell growth in vitro and in vivo.
      CONCLUSIONS: These results provide a new model for USP7 deubiquitinase activity
      through recruitment to oncogenic chromatin loci and regulation of both oncogenic
      transcription factors and chromatin marks to promote leukemia. Our studies also
      show that targeting USP7 inhibition could be a therapeutic strategy in aggressive
      leukemia.

PMID- 30224339
TI  - NOTCH1 Represses MCL-1 Levels in GSI-resistant T-ALL, Making them Susceptible to
      ABT-263.
AB  - Purpose: Effective targeted therapies are lacking for refractory and relapsed T
      cell acute lymphoblastic leukemia (T-ALL). Suppression of the NOTCH pathway using
      gamma-secretase inhibitors (GSI) is toxic and clinically not effective. The goal
      of this study was to identify alternative therapeutic strategies for T
      ALL.Experimental Design: We performed a comprehensive analysis of our high
      throughput drug screen across hundreds of human cell lines including 15 T-ALL
      models. We validated and further studied the top hit, navitoclax (ABT-263). We
      used multiple human T-ALL cell lines as well as primary patient samples, and
      performed both in vitro experiments and in vivo studies on patient-derived
      xenograft models.Results: We found that T-ALL are hypersensitive to navitoclax,
      an inhibitor of BCL2 family of antiapoptotic proteins. Importantly, GSI-resistant
      T-ALL are also susceptible to navitoclax. Sensitivity to navitoclax is due to low
      levels of MCL-1 in T-ALL. We identify an unsuspected regulation of mTORC1 by the
      NOTCH pathway, resulting in increased MCL-1 upon GSI treatment. Finally, we show
      that pharmacologic inhibition of mTORC1 lowers MCL-1 levels and further
      sensitizes cells to navitoclax in vitro and leads to tumor regressions in vivo
      Conclusions: Our results support the development of navitoclax, as single agent
      and in combination with mTOR inhibitors, as a new therapeutic strategy for T-ALL,
      including in the setting of GSI resistance. Clin Cancer Res; 1-13. (c)2018 AACR.

PMID- 30224340
TI  - Tracking Cell Transplants in Femoral Osteonecrosis with Magnetic Resonance
      Imaging: A Proof-of-Concept Study in Patients.
AB  - Purpose: Osteonecrosis is a devastating complication of high-dose corticosteroid
      therapy in patients with cancer. Core decompression for prevention of bone
      collapse has been recently combined with the delivery of autologous concentrated
      bone marrow aspirates. The purpose of our study was to develop an imaging test
      for the detection of transplanted bone marrow cells in osteonecrosis
      lesions.Experimental Design: In a prospective proof-of-concept clinical trial
      (NCT02893293), we performed serial MRI studies of nine hip joints of 7 patients
      with osteonecrosis before and after core decompression. Twenty-four to 48 hours
      prior to the surgery, we injected ferumoxytol nanoparticles intravenously to
      label cells in normal bone marrow with iron oxides. During the surgery, iron
      labeled bone marrow cells were aspirated from the iliac crest, concentrated, and
      then injected into the decompression track. Following surgery, patients received
      follow-up MRI up to 6 months after bone marrow cell transplantation.Results: Iron
      labeled cells could be detected in the access canal by a dark (negative) signal
      on T2-weighted MR images. T2* relaxation times of iron-labeled cell transplants
      were significantly lower compared with unlabeled cell transplants of control
      patients who were not injected with ferumoxytol (P = 0.02). Clinical outcomes of
      patients who received ferumoxytol-labeled or unlabeled cell transplants were not
      significantly different (P = 1), suggesting that the added ferumoxytol
      administration did not negatively affect bone repair.Conclusions: This
      immediately clinically applicable imaging test could become a powerful new tool
      to monitor the effect of therapeutic cells on bone repair outcomes after
      corticosteroid-induced osteonecrosis. Clin Cancer Res; 1-7. (c)2018 AACR.

PMID- 30224341
TI  - MAVERICC, a Randomized, Biomarker-stratified, Phase II Study of mFOLFOX6
      Bevacizumab versus FOLFIRI-Bevacizumab as First-line Chemotherapy in Metastatic
      Colorectal Cancer.
AB  - Purpose: MAVERICC compared the efficacy and safety of modified leucovorin/5
      fluorouracil/oxaliplatin plus bevacizumab (mFOLFOX6-BV) with leucovorin/5
      fluorouracil/irinotecan plus bevacizumab (FOLFIRI-BV) in patients with previously
      untreated metastatic colorectal cancer (mCRC).Experimental Design: MAVERICC was a
      global, randomized, open-label, phase II study. Primary objectives were to assess
      associations between (i) excision repair cross-complementing 1 (ERCC1) expression
      with progression-free survival (PFS), and (ii) plasma VEGF A (VEGF-A) with PFS in
      patients with previously untreated mCRC receiving mFOLFOX6-BV or FOLFIRI-BV.
      Before randomization, patients were stratified by tumoral ERCC1/beta-actin mRNA
      expression level and region.Results: Of 376 enrolled patients, 188 each received
      mFOLFOX6-BV and FOLFIRI-BV. PFS and overall survival (OS) were comparable between
      FOLFIRI-BV and mFOLFOX6-BV, with numerically higher PFS [HR = 0.79; 95% CI
      (confidence interval): 0.61-1.01; P = 0.06] and OS (HR = 0.76; 95% CI: 0.56-1.04;
      P = 0.09) observed for FOLFIRI-BV. In the high ERCC1 subgroup, PFS and OS were
      comparable between treatment groups (PFS, HR = 0.84; 95% CI: 0.56-1.26; P = 0.40;
      OS, HR = 0.80; 95% CI: 0.51-1.26; P = 0.33). Across treatment groups, high plasma
      VEGF-A levels (>5.1 pg/mL) were observed with shorter PFS (HR = 1.19; 95% CI:
      0.93-1.53; P = 0.17) and significantly shorter OS (HR = 1.64; 95% CI: 1.20-2.24;
      P < 0.01) versus low levels (<=5.1 pg/mL). Safety findings for FOLFIRI-BV or
      mFOLFOX6-BV were comparable with those reported previously.Conclusions: First
      line FOLFIRI-BV and mFOLFOX6-BV had comparable PFS and OS, similar to results in
      patients with high baseline tumor ERCC1 levels. There were no new safety signals
      with these bevacizumab-containing regimens. Clin Cancer Res; 1-8. (c)2018 AACR.

PMID- 30224342
TI  - Impact of BRAF Mutation Class on Disease Characteristics and Clinical Outcomes in
      BRAF-mutant Lung Cancer.
AB  - Purpose: BRAF mutations are divided into functional classes distinguished by
      signaling mechanism and kinase activity: V600-mutant kinase-activating monomers
      (class I), kinase-activating dimers (class II), and kinase-inactivating
      heterodimers (class III). The relationship between functional class and disease
      characteristics in BRAF-mutant non-small cell lung cancer (NSCLC) has not been
      fully explored.Experimental Design: We performed a retrospective analysis of BRAF
      mutant NSCLCs treated at 2 institutions from 2005 to 2017 to determine
      clinicopathologic characteristics, progression-free survival (PFS) on
      chemotherapy, and overall survival (OS).Results: We identified 236 patients with
      BRAF-mutant NSCLC (n = 107 class I, n = 75 class II, and n = 54 class III).
      Patients with class II or III mutations were more likely to have brain metastases
      (P <= 0.01) and RAS coalterations (P <= 0.001) than class I. Compared with class
      I, PFS on chemotherapy was shorter for class II (P = 0.069) and class III (P =
      0.034). OS was shorter for class II and III (class I, 40.1 months; class II, 13.9
      months; and class III, 15.6 months; I vs. II, P < 0.001; I vs. III, P = 0.023);
      however, this difference was driven by fewer extrathoracic metastases and higher
      use of targeted therapies in class I patients. When patients treated with
      targeted therapy and those with thoracic-only metastases were excluded, there was
      no difference in OS across the 3 classes.Conclusions: BRAF-mutant NSCLC is a
      heterogeneous disease that encompasses 3 distinct functional classes. Classes II
      and III have more aggressive clinical features leading to less favorable
      outcomes. The distinct biological characteristics of class II and III tumors
      suggest that class-specific therapies may be necessary to effectively target
      these molecular subsets. Clin Cancer Res; 1-8. (c)2018 AACR.

PMID- 30224343
TI  - The Anatomical Location Shapes the Immune Infiltrate in Tumors of Same Etiology
      and Affects Survival.
AB  - Purpose: The tumor immune microenvironment determines clinical outcome. Whether
      the original tissue in which a primary tumor develops influences this
      microenvironment is not well understood.Experimental Design: We applied high
      dimensional single-cell mass cytometry [Cytometry by Time-Of-Flight (CyTOF)]
      analysis and functional studies to analyze immune cell populations in human
      papillomavirus (HPV)-induced primary tumors of the cervix (cervical carcinoma)
      and oropharynx (oropharyngeal squamous cell carcinoma, OPSCC).Results: Despite
      the same etiology of these tumors, the composition and functionality of their
      lymphocytic infiltrate substantially differed. Cervical carcinoma displayed a 3
      fold lower CD4:CD8 ratio and contained more activated CD8+CD103+CD161+ effector T
      cells and less CD4+CD161+ effector memory T cells than OPSCC. CD161+ effector
      cells produced the highest cytokine levels among tumor-specific T cells.
      Differences in CD4+ T-cell infiltration between cervical carcinoma and OPSCC were
      reflected in the detection rate of intratumoral HPV-specific CD4+ T cells and in
      their impact on OPSCC and cervical carcinoma survival. The peripheral blood
      mononuclear cell composition of these patients, however, was similar.Conclusions:
      The tissue of origin significantly affects the overall shape of the immune
      infiltrate in primary tumors. Clin Cancer Res; 1-13. (c)2018 AACR.

PMID- 30224344
TI  - Divergent biological response to neoadjuvant chemotherapy in muscle-invasive
      bladder cancer.
AB  - PURPOSE: After cisplatin-based neoadjuvant chemotherapy (NAC) 60% of patients
      with muscle-invasive bladder cancer still have residual invasive disease at
      radical cystectomy (RC). The NAC-induced biological alterations in these
      cisplatin-resistant tumors remain largely unstudied. EXPERIMENTAL DESIGN: RC
      samples were available for gene expression analysis from 133 patients with
      residual invasive disease after cisplatin-based NAC, of whom 116 had matched pre
      NAC samples. Unsupervised consensus clustering (CC) was performed and the CC were
      investigated for their biological and clinical characteristics. H&E and
      immunohistochemistry on tissue microarrays were used to confirm tissue sampling
      and gene expression analysis. RESULTS: Established molecular subtyping models
      proved to be inconsistent in their classification of the post-NAC samples.
      Unsupervised consensus clustering revealed four distinct consensus clusters (CC).
      The CC1-Basal and CC2-Luminal subtypes expressed genes consistent with a basal
      and a luminal phenotype, respectively, and were similar to the corresponding
      established pre-treatment molecular subtypes. The CC3-Immune subtype had the
      highest immune activity, including T-cell infiltration and checkpoint molecule
      expression, but lacked both basal and luminal markers. The CC4-Scar-like subtype
      expressed genes associated with wound-healing/ scarring, although the proportion
      of tumor cell content in this subtype did not differ from the other subtypes.
      Patients with CC4-Scar-like tumors had the most favorable prognosis. CONCLUSION:
      This study expands our knowledge on muscle-invasive bladder cancer not responding
      to cisplatin by suggesting molecular subtypes to understand the biology of these
      tumors. Although these molecular subtypes imply consequences for adjuvant
      treatments, this ultimately needs to be tested in clinical trials.

PMID- 30224345
TI  - Epigenetic Therapy with Panobinostat Combined with Bicalutamide Rechallenge in
      Castration-Resistant Prostate Cancer.
AB  - Purpose: This study assesses the action of panobinostat, a histone deacetylase
      inhibitor (HDACI), in restoring sensitivity to bicalutamide in a castration
      resistant prostate cancer (CRPC) model and the efficacy and safety of the
      panobinostat/bicalutamide combination in CRPC patients resistant to second-line
      antiandrogen therapy (2ndLAARx).Patients and Methods: The CWR22PC xenograft and
      isogenic cell line were tested for drug interactions on tumor cell growth and on
      the androgen receptor (AR), AR-splice variant7, and AR targets. A phase I trial
      had a 3 * 3 panobinostat dose-escalation design. The phase II study randomized 55
      patients to panobinostat 40 mg (A arm) or 20 mg (B arm) triweekly *2 weeks with
      bicalutamide 50 mg/day in 3-week cycles. The primary endpoint was to determine
      the percentage of radiographic progression-free (rPF) patients at 36 weeks versus
      historic high-dose bicalutamide.Results: In the model, panobinostat/bicalutamide
      demonstrated synergistic antitumor effect while reducing AR activity. The dose
      limiting toxicity was not reached. The probability of remaining rPF exceeded
      protocol-specified 35% in the A arm and 47.5% and 38.5% in the B arm. The
      probabilities of remaining rPF were 47.5% in the A arm and 38.5% in the B arm,
      exceeding the protocol-specified threshold of 35%. A arm/B arm: adverse events
      (AE), 62%/19%; treatment stopped for AEs, 27.5%/11.5%; dose reduction required,
      41%/4%; principal A-arm grade >=3 AEs, thrombocytopenia (31%) and fatigue
      (14%).Conclusions: The 40 mg panobinostat/bicalutamide regimen increased rPF
      survival in CRPC patients resistant to 2ndLAARx. Panobinostat toxicity was
      tolerable with dose reductions. Epigenetic HDACI therapy reduces AR-mediated
      resistance to bicalutamide in CRPC models with clinical benefit in patients. The
      combination merits validation using a second-generation antiandrogen. Clin Cancer
      Res; 1-12. (c)2018 AACR.

PMID- 30224346
TI  - Urinary angiotensinogen predicts progressive chronic kidney disease after an
      episode of experimental acute kidney injury.
AB  - One of the major obstacles to prevent AKI-CKD transition is the lack of effective
      methods to follow and predict the ongoing kidney injury after an AKI episode. In
      the present study, we test the utility of urinary angiotensinogen (UAGT) for
      dynamically evaluating renal structural changes and predicting AKI-CKD
      progression by using both mild and severe bilateral renal ischemia/reperfusion
      injury mice. UAGT returns to pre-ischemic levels 14 days after mild AKI followed
      by kidney architecture restoration, whereas sustained increase in UAGT
      accompanies by ongoing renal fibrosis after severe AKI. UAGT at day 14-42
      correlates with renal fibrosis 84 days after AKI. For predicting fibrosis at day
      84, the area under receiver operating characteristics curve of UAGT at day 14 is
      0.81. Persistent elevation in UAGT correlates with sustained activation of
      intrarenal renin-angiotensin system (RAS) during AKI-CKD transition. Abrogating
      RAS activation post AKI markedly reduced renal fibrosis, with early RAS
      intervention (from 14 days after IRI) more beneficial than late intervention
      (from 42 days after IRI) in alleviating fibrosis. Importantly, UAGT decreases
      after RAS intervention, and its level at day 14-28 correlates with the extent of
      renal fibrosis at day 42 post RAS blockade. A pilot study conducted in patients
      with acute tubular necrosis finds that compared with those recovered, patients
      with AKI-CKD progression exhibits elevated UAGT during the 3-month follow-up
      after biopsy. Our study suggests that UAGT enables the dynamical monitoring of
      renal structural recovery after an AKI episode and may serve as an early
      predictor for AKI-CKD progression and treatment response.

PMID- 30224347
TI  - Gut Microbiota Differs in Composition and Functionality Between Children With
      Type 1 Diabetes and MODY2 and Healthy Control Subjects: A Case-Control Study.
AB  - OBJECTIVE: Type 1 diabetes is associated with compositional differences in gut
      microbiota. To date, no microbiome studies have been performed in maturity-onset
      diabetes of the young 2 (MODY2), a monogenic cause of diabetes. Gut microbiota of
      type 1 diabetes, MODY2, and healthy control subjects was compared. RESEARCH
      DESIGN AND METHODS: This was a case-control study in 15 children with type 1
      diabetes, 15 children with MODY2, and 13 healthy children. Metabolic control and
      potential factors modifying gut microbiota were controlled. Microbiome
      composition was determined by 16S rRNA pyrosequencing. RESULTS: Compared with
      healthy control subjects, type 1 diabetes was associated with a significantly
      lower microbiota diversity, a significantly higher relative abundance of
      Bacteroides, Ruminococcus, Veillonella, Blautia, and Streptococcus genera, and a
      lower relative abundance of Bifidobacterium, Roseburia, Faecalibacterium, and
      Lachnospira. Children with MODY2 showed a significantly higher Prevotella
      abundance and a lower Ruminococcus and Bacteroides abundance. Proinflammatory
      cytokines and lipopolysaccharides were increased in type 1 diabetes, and gut
      permeability (determined by zonulin levels) was significantly increased in type 1
      diabetes and MODY2. The PICRUSt analysis found an increment of genes related to
      lipid and amino acid metabolism, ABC transport, lipopolysaccharide biosynthesis,
      arachidonic acid metabolism, antigen processing and presentation, and chemokine
      signaling pathways in type 1 diabetes. CONCLUSIONS: Gut microbiota in type 1
      diabetes differs at taxonomic and functional levels not only in comparison with
      healthy subjects but fundamentally with regard to a model of nonautoimmune
      diabetes. Future longitudinal studies should be aimed at evaluating if the
      modulation of gut microbiota in patients with a high risk of type 1 diabetes
      could modify the natural history of this autoimmune disease.

PMID- 30224348
TI  - Glucose Management Indicator (GMI): A New Term for Estimating A1C From Continuous
      Glucose Monitoring.
AB  - While A1C is well established as an important risk marker for diabetes
      complications, with the increasing use of continuous glucose monitoring (CGM) to
      help facilitate safe and effective diabetes management, it is important to
      understand how CGM metrics, such as mean glucose, and A1C correlate. Estimated
      A1C (eA1C) is a measure converting the mean glucose from CGM or self-monitored
      blood glucose readings, using a formula derived from glucose readings from a
      population of individuals, into an estimate of a simultaneously measured
      laboratory A1C. Many patients and clinicians find the eA1C to be a helpful
      educational tool, but others are often confused or even frustrated if the eA1C
      and laboratory-measured A1C do not agree. In the U.S., the Food and Drug
      Administration determined that the nomenclature of eA1C needed to change. This
      led the authors to work toward a multipart solution to facilitate the retention
      of such a metric, which includes renaming the eA1C the glucose management
      indicator (GMI) and generating a new formula for converting CGM-derived mean
      glucose to GMI based on recent clinical trials using the most accurate CGM
      systems available. The final aspect of ensuring a smooth transition from the old
      eA1C to the new GMI is providing new CGM analyses and explanations to further
      understand how to interpret GMI and use it most effectively in clinical practice.
      This Perspective will address why a new name for eA1C was needed, why GMI was
      selected as the new name, how GMI is calculated, and how to understand and
      explain GMI if one chooses to use GMI as a tool in diabetes education or
      management.

PMID- 30224350
TI  - Osimertinib Treats CNS Metastases in NSCLC.
AB  - The EGFR inhibitor osimertinib may be an effective therapy for patients with
      untreated non-small cell lung cancer who have brain metastases. In a recent
      study, the drug extended median progression-free survival and increased objective
      response rates compared with the first-generation EGFR inhibitors gefitinib and
      erlotinib.

PMID- 30224349
TI  - A sequence-based, deep learning model accurately predicts RNA splicing
      branchpoints.
AB  - Experimental detection of RNA splicing branchpoints is difficult. To date, high
      confidence experimental annotations exist for 18% of 3' splice sites in the human
      genome. We develop a deep-learning-based branchpoint predictor, LaBranchoR, which
      predicts a correct branchpoint for at least 75% of 3' splice sites genome-wide.
      Detailed analysis of cases in which our predicted branchpoint deviates from
      experimental data suggests a correct branchpoint is predicted in over 90% of
      cases. We use our predicted branchpoints to identify a novel sequence element
      upstream of branchpoints consistent with extended U2 snRNA base-pairing, show an
      association between weak branchpoints and alternative splicing, and explore the
      effects of genetic variants on branchpoints. We provide genome-wide branchpoint
      annotations and in silico mutagenesis scores at
      http://bejerano.stanford.edu/labranchor.

PMID- 30224351
TI  - Severe hand-foot skin reaction and erythema multiforme-like lesions due to
      sorafenib.

PMID- 30224322
TI  - Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR):
      a multicentre, prospective observational study.
AB  - BACKGROUND: Results from retrospective studies suggest that use of neuromuscular
      blocking agents during general anaesthesia might be linked to postoperative
      pulmonary complications. We therefore aimed to assess whether the use of
      neuromuscular blocking agents is associated with postoperative pulmonary
      complications. METHODS: We did a multicentre, prospective observational cohort
      study. Patients were recruited from 211 hospitals in 28 European countries. We
      included patients (aged >=18 years) who received general anaesthesia for any in
      hospital procedure except cardiac surgery. Patient characteristics, surgical and
      anaesthetic details, and chart review at discharge were prospectively collected
      over 2 weeks. Additionally, each patient underwent postoperative physical
      examination within 3 days of surgery to check for adverse pulmonary events. The
      study outcome was the incidence of postoperative pulmonary complications from the
      end of surgery up to postoperative day 28. Logistic regression analyses were
      adjusted for surgical factors and patients' preoperative physical status,
      providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction
      (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513.
      FINDINGS: Between June 16, 2014, and April 29, 2015, data from 22 803 patients
      were collected. The use of neuromuscular blocking agents was associated with an
      increased incidence of postoperative pulmonary complications in patients who had
      undergone general anaesthesia (1658 [7.6%] of 21 694); ORadj 1.86, 95% CI 1.53
      2.26; ARRadj -4.4%, 95% CI -5.5 to -3.2). Only 2.3% of high-risk surgical
      patients and those with adverse respiratory profiles were anaesthetised without
      neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1.31,
      95% CI 1.15-1.49; ARRadj -2.6%, 95% CI -3.9 to -1.4) and the administration of
      reversal agents (1.23, 1.07-1.41; -1.9%, -3.2 to -0.7) were not associated with a
      decreased risk of postoperative pulmonary complications. Neither the choice of
      sugammadex instead of neostigmine for reversal (ORadj 1.03, 95% CI 0.85-1.25;
      ARRadj -0.3%, 95% CI -2.4 to 1.5) nor extubation at a train-of-four ratio of 0.9
      or more (1.03, 0.82-1.31; -0.4%, -3.5 to 2.2) was associated with better
      pulmonary outcomes. INTERPRETATION: We showed that the use of neuromuscular
      blocking drugs in general anaesthesia is associated with an increased risk of
      postoperative pulmonary complications. Anaesthetists must balance the potential
      benefits of neuromuscular blockade against the increased risk of postoperative
      pulmonary complications. FUNDING: European Society of Anaesthesiology.

PMID- 30224352
TI  - Over 1200 NHS staff have been disciplined for social media use.

PMID- 30224353
TI  - Characterization of Lhr-Core DNA helicase and manganese- dependent DNA nuclease
      components of a bacterial gene cluster encoding nucleic acid repair enzymes.
AB  - Lhr is a large superfamily 2 helicase present in mycobacteria and a moderate
      range of other bacterial taxa. A shorter version of Lhr, here referred to as Lhr
      Core, is distributed widely in bacteria, where it is often encoded in a gene
      cluster along with predicted binuclear metallo-phosphoesterase (MPE), ATP
      dependent DNA ligase, and metallo-beta-lactamase exonuclease enzymes. Here we
      characterized the Lhr-Core and MPE proteins from Pseudomonas putida We report
      that P. putida Lhr-Core is an ssDNA-dependent ATPase/dATPase (Km , 0.37 mm ATP; k
      cat, 3.3 s-1), an ATP-dependent 3'-to-5' single-stranded DNA translocase, and an
      ATP-dependent 3'-to-5' helicase. Lhr-Core unwinds 3'-tailed duplexes in which the
      loading/tracking strand is DNA and the displaced strand is either DNA or RNA. We
      found that P. putida MPE is a manganese-dependent phosphodiesterase that releases
      p-nitrophenol from bis-p-nitrophenyl phosphate (k cat, 212 s-1) and p-nitrophenyl
      5'-thymidylate (k cat, 34 s-1) but displays no detectable phosphomonoesterase
      activity against p-nitrophenyl phosphate. MPE is also a manganese-dependent DNA
      endonuclease that sequentially converts a closed-circle plasmid DNA to nicked
      circle and linear forms prior to degrading the linear DNA to produce
      progressively smaller fragments. The biochemical activities of MPE and a
      structure predicted in Phyre2 point to MPE as a new bacterial homolog of Mre11.
      Genetic linkage of a helicase and DNA nuclease with a ligase and a putative
      exonuclease (a predicted homolog of the SNM1/Apollo family of nucleases) suggests
      that these enzymes comprise or participate in a bacterial DNA repair pathway.

PMID- 30224354
TI  - Identification, functional characterization, and crystal structure determination
      of bacterial levoglucosan dehydrogenase.
AB  - Levoglucosan is the 1,6-anhydrosugar of d-glucose formed by pyrolysis of glucans
      and is found in the environment and industrial waste. Two types of microbial
      levoglucosan metabolic pathways are known. Although the eukaryotic pathway
      involving levoglucosan kinase has been well-studied, the bacterial pathway
      involving levoglucosan dehydrogenase (LGDH) has not been well-investigated. Here,
      we identified and cloned the lgdh gene from the bacterium Pseudarthrobacter
      phenanthrenivorans and characterized the recombinant protein. The enzyme
      exhibited high substrate specificity toward levoglucosan and NAD+ for the
      oxidative reaction and was confirmed to be LGDH. LGDH also showed weak activities
      (~4%) toward l-sorbose and 1,5-anhydro-d-glucitol. The reverse (reductive)
      reaction using 3-keto-levoglucosan and NADH exhibited significantly lower Km and
      higher k cat values than those of the forward reaction. The crystal structures of
      LGDH in the apo and complex forms with NADH, NADH + levoglucosan, and NADH + l
      sorbose revealed that LGDH has a typical fold of Gfo/Idh/MocA family proteins,
      similar to those of scyllo-inositol dehydrogenase, aldose-aldose oxidoreductase,
      1,5-anhydro-d-fructose reductase, and glucose-fructose oxidoreductase. The
      crystal structures also disclosed that the active site of LGDH is distinct from
      those of these enzymes. The LGDH active site extensively recognized the
      levoglucosan molecule with six hydrogen bonds, and the C3 atom of levoglucosan
      was closely located to the C4 atom of NADH nicotinamide. Our study is the first
      molecular characterization of LGDH, providing evidence for C3-specific oxidation
      and representing a starting point for future biotechnological use of LGDH and
      levoglucosan-metabolizing bacteria.

PMID- 30224355
TI  - Cox2p of yeast cytochrome oxidase assembles as a stand-alone subunit with the
      Cox1p and Cox3p modules.
AB  - Cytochrome oxidase (COX) is a hetero-oligomeric complex of the mitochondrial
      inner membrane that reduces molecular oxygen to water, a reaction coupled to
      proton transfer from the mitochondrial matrix to the intermembrane space. In the
      yeast Saccharomyces cerevisiae, COX is composed of 11-13 different polypeptide
      subunits. Here, using pulse labeling of mitochondrial gene products in isolated
      yeast mitochondria, combined with purification of tagged COX subunits and
      ancillary factors, we studied the Cox2p assembly intermediates. Analysis of
      radiolabeled Cox2p obtained in pulldown assays by native gel electrophoresis
      revealed the existence of several assembly intermediates, the largest of which
      had an estimated mass of 450-550 kDa. None of the other known subunits of COX
      were present in these Cox2p intermediates. This was also true for the several
      ancillary factors having still undefined functions in COX assembly. In agreement
      with earlier evidence, Cox18p and Cox20p, previously shown to be involved in
      processing and in membrane insertion of the Cox2p precursor, were found to be
      associated with the two largest Cox2p intermediates. A small fraction of the
      Cox2p module contained Sco1p and Coa6p, which have been implicated in metalation
      of the binuclear copper site on this subunit. Our results indicate that following
      its insertion into the mitochondrial inner membrane, Cox2p assembles as a stand
      alone protein with the compositionally more complex Cox1p and Cox3p modules.

PMID- 30224356
TI  - A DNA nick at Ku-blocked double-strand break ends serves as an entry site for
      exonuclease 1 (Exo1) or Sgs1-Dna2 in long-range DNA end resection.
AB  - The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is
      initiated by nucleolytic resection of the DNA break ends. The current model,
      being based primarily on genetic analyses in Saccharomyces cerevisiae and
      companion biochemical reconstitution studies, posits that end resection proceeds
      in two distinct stages. Specifically, the initiation of resection is mediated by
      the nuclease activity of the Mre11-Rad50-Xrs2 (MRX) complex in conjunction with
      its cofactor Sae2, and long-range resection is carried out by exonuclease 1
      (Exo1) or the Sgs1-Top3-Rmi1-Dna2 ensemble. Using fully reconstituted systems, we
      show here that DNA with ends occluded by the DNA end-joining factor Ku70-Ku80
      becomes a suitable substrate for long-range 5'-3' resection when a nick is
      introduced at a locale proximal to one of the Ku-bound DNA ends. We also show
      that Sgs1 can unwind duplex DNA harboring a nick, in a manner dependent on a
      species-specific interaction with the ssDNA-binding factor replication protein A
      (RPA). These biochemical systems and results will be valuable for guiding future
      endeavors directed at delineating the mechanistic intricacy of DNA end resection
      in eukaryotes.

PMID- 30224358
TI  - The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous
      OGT:UDP-GlcNAc glycosylation and proteolysis activities.
AB  - O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease
      activities. OGT thereby stably glycosylates serines and threonines of numerous
      proteins and, via a transient glutamate glycosylation, cleaves a single known
      substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host
      cell factor 1 (HCF-1). Here, we probed the relationship between these distinct
      glycosylation and proteolytic activities. For proteolysis, the HCF-1PRO repeat
      possesses an important extended threonine-rich region that is tightly bound by
      the OGT tetratricopeptide-repeat (TPR) region. We report that linkage of this HCF
      1PRO-repeat, threonine-rich region to heterologous substrate sequences also
      potentiates robust serine glycosylation with the otherwise poor R p-alphaS-UDP
      GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
      Furthermore, it potentiated proteolysis of a non-HCF-1PRO-repeat cleavage
      sequence, provided it contained an appropriately positioned glutamate residue.
      Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that
      proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation
      mechanisms can be circumvented independently, but not when disrupted together. In
      contrast, disruption of both proposed activation mechanisms even in combination
      did not inhibit OGT-mediated proteolysis. These results reveal a multiplicity of
      OGT glycosylation strategies, some leading to proteolysis, which could be targets
      of alternative molecular regulatory strategies.

PMID- 30224360
TI  - How Superantigens Bind MHC.

PMID- 30224357
TI  - Altered oligomeric states in pathogenic ALS2 variants associated with juvenile
      motor neuron diseases cause loss of ALS2-mediated endosomal function.
AB  - Familial amyotrophic lateral sclerosis type 2 (ALS2) is a juvenile autosomal
      recessive motor neuron disease caused by the mutations in the ALS2 gene. The ALS2
      gene product, ALS2/alsin, forms a homophilic oligomer and acts as a guanine
      nucleotide-exchange factor (GEF) for the small GTPase Rab5. This oligomerization
      is crucial for both Rab5 activation and ALS2-mediated endosome fusion and
      maturation in cells. Recently, we have shown that pathogenic missense ALS2
      mutants retaining the Rab5 GEF activity fail to properly localize to endosomes
      via Rac1-stimulated macropinocytosis. However, the molecular mechanisms
      underlying dysregulated distribution of ALS2 variants remain poorly understood.
      Therefore, we sought to clarify the relationship between intracellular
      localization and oligomeric states of pathogenic ALS2 variants. Upon Rac family
      small GTPase 1 (Rac1) activation, all mutants tested moved from the cytosol to
      membrane ruffles but not to macropinosomes and/or endosomes. Furthermore, most WT
      ALS2 complexes were tetramers. Importantly, the sizes of an ALS2 complex carrying
      missense mutations in the N terminus of the regulator of chromosome condensation
      1-like domain (RLD) or in-frame deletion in the pleckstrin homology domain were
      shifted toward higher molecular weight, whereas the C-terminal vacuolar protein
      sorting 9 (VPS9) domain missense mutant existed as a smaller dimeric or trimeric
      smaller form. Furthermore, in silico mutagenesis analyses using the RLD protein
      structure in conjunction with a cycloheximide chase assay in vitro disclosed that
      these missense mutations led to a decrease in protein stability. Collectively,
      disorganized higher structures of ALS2 variants might explain their impaired
      endosomal localization and the stability, leading to loss of the ALS2 function.

PMID- 30224359
TI  - Flow Cytometry: To Dump or Not To Dump.

PMID- 30224361
TI  - Pillars Article: Three-Dimensional Structure of a Human Class II
      Histocompatibility Molecule Complexed with Superantigen. Nature. 1994. 368: 711
      718.

PMID- 30224363
TI  - Ensuring Comprehensive Care and Support for Transgender and Gender-Diverse
      Children and Adolescents.
AB  - As a traditionally underserved population that faces numerous health disparities,
      youth who identify as transgender and gender diverse (TGD) and their families are
      increasingly presenting to pediatric providers for education, care, and
      referrals. The need for more formal training, standardized treatment, and
      research on safety and medical outcomes often leaves providers feeling ill
      equipped to support and care for patients that identify as TGD and families. In
      this policy statement, we review relevant concepts and challenges and provide
      suggestions for pediatric providers that are focused on promoting the health and
      positive development of youth that identify as TGD while eliminating
      discrimination and stigma.

PMID- 30224364
TI  - The Transition Journey: Time to Systematically Address Transition Planning to
      Adult Health Care.

PMID- 30224365
TI  - Infant Walker-Related Injuries in the United States.
AB  - OBJECTIVES: To investigate the epidemiologic characteristics of infant walker
      related injuries among children <15 months old who were treated in US emergency
      departments and to evaluate the effect of the 2010 federal mandatory safety
      standard on these injuries. METHODS: National Electronic Injury Surveillance
      System data from 1990 to 2014 were analyzed. RESULTS: An estimated 230 676
      children <15 months old were treated for infant walker-related injuries in US
      emergency departments from 1990 to 2014. Most of the children sustained head or
      neck injuries (90.6%) and 74.1% were injured by falling down the stairs in an
      infant walker. Among patients who were admitted to the hospital (4.5%), 37.8% had
      a skull fracture. From 1990 to 2003, overall infant walker-related injuries and
      injuries related to falling down the stairs decreased by 84.5% and 91.0%,
      respectively. The average annual number of injuries decreased by 22.7% (P = .019)
      during the 4-year period after the implementation of the federal mandatory safety
      standard compared with the 4-year period before the standard. CONCLUSIONS: Infant
      walker-related injuries decreased after the implementation of the federal
      mandatory safety standard in 2010. This decrease may, in part, be attributable to
      the standard as well as other factors, such as decreased infant walker use and
      fewer older infant walkers in homes. Despite the decline in injuries, infant
      walkers remain an important and preventable source of injury among young
      children, which supports the American Academy of Pediatrics' call for a ban on
      their manufacture and sale in the United States.

PMID- 30224362
TI  - Innate T Cells Govern Adipose Tissue Biology.
AB  - During the past 25 y, the immune system has appeared as a key regulator of
      adipose tissue biology and metabolic homeostasis. In lean animals, adipose
      resident leukocytes maintain an anti-inflammatory microenvironment that preserves
      the proper functioning of the tissue. In this review, we describe two populations
      of innate T cells enriched in adipose tissue, invariant NKT and gammadelta T
      cells, and how they serve overlapping and nonredundant roles in controlling
      adipose tissue functions. These cells interact with and expand anti-inflammatory
      regulatory T cells and M2 macrophages, thereby driving a metabolically beneficial
      tissue milieu. Surprisingly, we have found that adipose invariant NKT and
      gammadelta T cells also promote weight loss and heat production in a process
      called "nonshivering thermogenesis." The data surrounding these two cell types
      highlight their powerful ability to regulate not only other leukocytes, but also
      tissue-wide processes that affect an entire organism.

PMID- 30224366
TI  - Transition Planning Among US Youth With and Without Special Health Care Needs.
AB  - BACKGROUND: Researchers have shown that most youth with special health care needs
      (YSHCN) are not receiving guidance on planning for health care transition. This
      study examines current transition planning among US youth with and without
      special health care needs (SHCN). METHODS: The 2016 National Survey of Children's
      Health is nationally representative and includes 20 708 youth (12-17 years old).
      Parents and/or caregivers were asked if transition planning occurred, based on
      the following elements: (1) doctor or other health care provider (HCP) discussed
      the eventual shift to an HCP who cares for adults, (2) an HCP actively worked
      with youth to gain self-care skills or understand changes in health care at age
      18, and (3) youth had time alone with an HCP during the last preventive visit.
      Sociodemographic and health system characteristics were assessed for associations
      with transition planning. RESULTS: Nationally, 17% of YSHCN and 14% of youth
      without SHCN met the overall transition measure. Older age (15-17 years) was the
      only sociodemographic factor associated with meeting the overall transition
      measure and individual elements for YSHCN and youth without SHCN. Other
      sociodemographic characteristics associated with transition planning differed
      among the 2 populations. Receipt of care coordination and a written plan was
      associated with transition planning for YSHCN. CONCLUSIONS: This study reveals
      that few youth with and without SHCN receive transition planning support. It
      underscores the need for HCPs to work with youth independently and in
      collaboration with parents and/or caregivers throughout adolescence to gain self
      care skills and prepare for adult-focused care.

PMID- 30224367
TI  - Charles Bonnet syndrome - disturbing 'playthings of the brain'.

PMID- 30224368
TI  - Ultrasound avoidance by flying antlions (Myrmeleontidae).
AB  - The acoustic arms race between insectivorous bats and their invertebrate prey has
      led to the convergent evolution of ultrasound hearing in seven orders of
      nocturnal insects. Upon hearing the echolocation calls of an approaching bat,
      such insects take defensive action. Here, we document a previously unknown sense
      of ultrasound hearing and phonotactic flight behaviour in the neuropteran family
      Myrmeleontidae (antlions). The antlion Myrmeleon hyalinus was presented with
      sound pulses at ultrasonic frequencies used by echolocating bats and its response
      thresholds in tethered flight determined. Behaviours included abdominal twitches,
      wing flicks, brief pauses in flight and flight cessation. Such behaviours create
      erratic evasive flight manoeuvres in other eared insects, particularly mantids
      and lacewings. Antlions responded best to ultrasound between 60 and 80 kHz (75 dB
      peSPL at 80 kHz), showing response thresholds similar to those of the related
      lacewings (Neuroptera, Chrysopidae). Yet, at lower ultrasonic frequencies (20-50
      kHz), antlions were far less sensitive than lacewings. Based on calculated
      response distances, we conclude that antlions respond only after having been
      detected by bats rather than using early evasive flights. We argue that the high
      response threshold for low-frequency ultrasound is adaptive for an insect that is
      mainly active close to and within vegetation, because a behavioural response to
      the lower ultrasonic frequencies used by high-flying bats would result in evasive
      action in the absence of actual predation risk.

PMID- 30224369
TI  - An exercise-induced improvement in isolated skeletal muscle contractility does
      not affect the performance-enhancing benefit of 70 umol l-1 caffeine treatment.
AB  - This study aimed to examine the effects of exercise-induced increases in skeletal
      muscle contractile performance on isolated skeletal muscle caffeine sensitivity
      in mice. CD1 mice (n=28; 30 weeks old) either served as controls or underwent 8
      weeks of voluntary wheel running. Following the treatment intervention, whole
      soleus (SOL) or a section of the costal diaphragm (DIA) was isolated from each
      mouse and tested to determine the effect of 70 umol l-1 caffeine on work loop
      power output. Although caffeine elicited a significant increase in power of both
      the SOL and the DIA relative to levels in a non-caffeine-treated control, the
      effect was not different between the experimental groups, despite the muscles of
      the trained group producing significantly greater muscle power. There was no
      significant relationship between training volume or baseline work loop power and
      the caffeine response. These results indicate that an exercise-induced increase
      in muscle performance did not influence the performance-enhancing effects of
      caffeine.

PMID- 30224370
TI  - Dietary canthaxanthin reduces xanthophyll uptake and red coloration in adult red
      legged partridges.
AB  - Carotenoids give color to conspicuous animal signals that are often the product
      of sexual selection. Knowledge of the mechanisms involved in carotenoid-based
      signaling is critical to understanding how these traits evolve. However, these
      mechanisms remain only partially understood. Carotenoids are usually viewed as
      scarce dietary antioxidants whose allocation to ornaments may trade off against
      health. This trade-off would ensure its reliability as a signal of individual
      quality. In the case of red (keto)carotenoids, the literature suggests that some
      species may show constraints in their uptake. Canthaxanthin is one of the most
      common ketocarotenoids in red ornaments of animals. It is often commercially used
      as a dietary supplement to obtain redder birds (e.g. poultry). We increased the
      dietary canthaxanthin levels in captive red-legged partridges (Alectoris rufa).
      This species shows red non-feathered parts mostly pigmented by another common
      ketocarotenoid: astaxanthin. We studied the impact on the uptake of carotenoids
      and vitamins and, finally, on coloration. We also tested the potential protective
      effect of canthaxanthin when exposing birds to a free radical generator (diquat).
      Canthaxanthin did not apparently protect birds from oxidative stress, but
      interfered with the absorption of yellow carotenoids (lutein and zeaxanthin).
      Zeaxanthin is a precursor of astaxanthin in enzymatic pathways, and their levels
      in tissues and eggs were lower in canthaxanthin-supplied birds. This led to lower
      astaxanthin levels in ornaments and paler coloration. As far as we know, this is
      the first report of a carotenoid supplementation decreasing animal coloration.
      The results have implications for understanding carotenoid-based signaling
      evolution, but also for improving husbandry/experimental procedures.

PMID- 30224371
TI  - Electrical interactions between photoreceptors in the compound eye of Periplaneta
      americana.
AB  - The compound eye of Periplaneta americana contains two spectral classes of
      photoreceptors: narrow-band UV-sensitive and broad-band green-sensitive. In
      intracellular recordings, stimulation of green-sensitive photoreceptors with
      flashes of relatively bright UV/violet light produced anomalous delayed
      depolarization after the end of the normal light response, whereas stimulation of
      UV-sensitive photoreceptors with green light elicited biphasic responses
      characterized by initial transient hyperpolarization followed by prolonged
      delayed depolarization. To explore the basis for these findings, we used RNA
      interference to selectively suppress expression of the genes encoding green opsin
      (GO1), UV opsin (UVO) or both. The hyperpolarizing component in UV-sensitive
      photoreceptors was eliminated and the delayed depolarization was reduced after
      GO1 knockdown, suggesting that the hyperpolarization represents fast inhibitory
      interactions between green- and UV-sensitive photoreceptors. Green-sensitive
      photoreceptor responses of GO1 knockdowns to flashes of UV/violet were almost
      exclusively biphasic, whereas residual responses to green had normal kinetics.
      Knockdown of UVO reduced the responses of UV-sensitive photoreceptors but had
      minor effects on delayed depolarization in green-sensitive photoreceptors.
      Angular sensitivity analysis indicated that delayed depolarization of green
      sensitive photoreceptors by violet light originates from excitation of (an)other
      photoreceptor(s) in the same ommatidium. The angle at which the maximal delayed
      depolarization was observed in green-sensitive photoreceptors stimulated with
      violet light did not match the angle of the maximal transient depolarization. In
      contrast, no significant mismatch was observed for delayed depolarization
      elicited by green light. These results suggest that the cellular sources of the
      normal transient and additional delayed depolarization by violet light are
      separate and distinct.

PMID- 30224372
TI  - Active touch in sea otters: in-air and underwater texture discrimination
      thresholds and behavioral strategies for paws and vibrissae.
AB  - Sea otters (Enhydra lutris) are marine predators that forage on a wide array of
      cryptic, benthic invertebrates. Observational studies and anatomical
      investigations of the sea otter somatosensory cortex suggest that touch is an
      important sense for detecting and capturing prey. Sea otters have two well
      developed tactile structures: front paws and facial vibrissae. In this study, we
      use a two-alternative forced choice paradigm to investigate tactile sensitivity
      of a sea otter subject's paws and vibrissae, both in air and under water. We
      corroborate these measurements by testing human subjects with the same
      experimental paradigm. The sea otter showed good sensitivity with both tactile
      structures, but better paw sensitivity (Weber fraction, c=0.14) than vibrissal
      sensitivity (c=0.24). The sea otter's sensitivity was similar in air and under
      water for paw (cair=0.12, cwater=0.15) and for vibrissae (cair=0.24,
      cwater=0.25). Relative to the human subjects we tested, the sea otter achieved
      similar sensitivity when using her paw and responded approximately 30-fold faster
      regardless of difficulty level. Relative to non-human mammalian tactile
      specialists, the sea otter achieved similar or better sensitivity when using
      either her paw or vibrissae and responded 1.5- to 15-fold faster near threshold.
      Our findings suggest that sea otters have sensitive, rapid tactile processing
      capabilities. This functional test of anatomy-based hypotheses provides a
      mechanistic framework to interpret adaptations and behavioral strategies used by
      predators to detect and capture cryptic prey in aquatic habitats.

PMID- 30224373
TI  - Activation of B-1 cells promotes tumor cell killing in the peritoneal cavity.
AB  - Metastatic cancer involving spread to the peritoneal cavity is referred to as
      peritoneal carcinomatosis and has a very poor prognosis. Activating the anti
      tumor immune response in the characteristically immune-suppressive peritoneal
      environment presents a potential strategy to treat this disease. In this study,
      we show that a toll-like receptor (TLR) and C-type lectin receptor (CLR) agonist
      pairing of monophosphoryl lipid A (MPL) and trehalose-6,6'-dicorynomycolate
      (TDCM) effectively inhibits tumor growth and ascites development in a mouse model
      of aggressive mammary cancer-induced peritoneal carcinomatosis. MPL/TDCM
      treatment similarly inhibited peritoneal EL4 tumor growth and ascites
      development. These effects were not observed in mice lacking B cells or mice
      lacking CD19, which are deficient in B-1a cells, an innate-like B cell population
      enriched in the peritoneal cavity. Remarkably, adoptive transfer of B-1a cells,
      but not splenic B cells from WT mice restored MPL/TDCM-induced protection in mice
      with B cell defects. Treatment induced B-1 cells to rapidly produce high levels
      of natural IgM reactive against tumor-associated carbohydrate antigens.
      Consistent with this, we found significant deposition of IgM and C3 on peritoneal
      tumor cells as early as 5 days post-treatment. Mice unable to secrete IgM or
      complement component C4 were not protected by MPL/TDCM treatment, indicating
      tumor killing was mediated by activation of the classical complement pathway.
      Collectively, our findings reveal an unsuspected role for B-1 cell-produced
      natural IgM in providing protection against tumor growth in the peritoneal
      cavity, thereby highlighting potential opportunities to develop novel therapeutic
      strategies for the prevention and treatment of peritoneal metastases.

PMID- 30224374
TI  - Evaluation of Explant Responses to STING Ligands: Personalized Immunosurgical
      Therapy for Head and Neck Squamous Cell Carcinoma.
AB  - Surgeons have unique in situ access to tumors enabling them to apply
      immunotherapies to resection margins as a means to prevent local recurrence.
      Here, we developed a surgical approach to deliver stimulator of interferon genes
      (STING) ligands to the site of a purposeful partial tumor resection using a gel
      based biomaterial. In a range of head and neck squamous cell carcinoma (HNSCC)
      murine tumor models, we demonstrate that although control-treated tumors recur
      locally, tumors treated with STING-loaded biomaterials are cured. The mechanism
      of tumor control required activation of STING and induction of type I IFN in host
      cells, not cancer cells, and resulted in CD8 T-cell-mediated cure of residual
      cancer cells. In addition, we used a novel tumor explant assay to screen
      individual murine and human HNSCC tumor responses to therapies ex vivo We then
      utilized this information to personalize the biomaterial and immunotherapy
      applied to previously unresponsive tumors in mice. These data demonstrate that
      explant assays identify the diversity of tumor-specific responses to STING
      ligands and establish the utility of the explant assay to personalize
      immunotherapies according to the local response.Significance: Delivery of
      immunotherapy directly to resection sites via a gel-based biomaterial prevents
      locoregional recurrence of head and neck squamous cell carcinoma. Cancer Res;
      78(21); 6308-19. (c)2018 AACR.

PMID- 30224376
TI  - Glycoprotein nmb Is Exposed on the Surface of Dormant Breast Cancer Cells and
      Induces Stem Cell-like Properties.
AB  - Glycoprotein nmb (GPNMB) is a type I transmembrane protein that contributes to
      the initiation and malignant progression of breast cancer through induction of
      epithelial-mesenchymal transition (EMT). Although it is known that EMT is
      associated with not only cancer invasion but also acquisition of cancer stem cell
      (CSC) properties, the function of GPNMB in this acquisition of CSC properties has
      yet to be elucidated. To address this issue, we utilized a three-dimensional (3D)
      sphere culture method to examine the correlation between GPNMB and CSC properties
      in breast cancer cells. Three-dimensional sphere cultures induced higher
      expression of CSC genes and EMT-inducing transcription factor (EMT-TF) genes than
      the 2D monolayer cultures. Three-dimensional culture also induced cell surface
      expression of GPNMB on limited numbers of cells in the spheres, whereas the 2D
      cultures did not. Therefore, we isolated cell surface-GPNMBhigh and -GPNMBlow
      cells from the spheres. Cell surface-GPNMBhigh cells expressed high levels of CSC
      genes and EMT-TF genes, had significantly higher sphere-forming frequencies than
      the cell surface-GPNMBlow cells, and showed no detectable levels of proliferation
      marker genes. Similar results were obtained from transplanted breast tumors.
      Furthermore, wild-type GPNMB, but not mutant GPNMB (YF), which lacks tumorigenic
      activity, induced CSC-like properties in breast epithelial cells. These findings
      suggest that GPNMB is exposed on the surface of dormant breast cancer cells and
      its activity contributes to the acquisition of stem cell-like
      properties.Significance: These findings suggest that cell surface expression of
      GPNMB could serve as a marker and promising therapeutic target of breast cancer
      cells with stem cell-like properties. Cancer Res; 78(22); 6424-35. (c)2018 AACR.

PMID- 30224375
TI  - UBE2N Promotes Melanoma Growth via MEK/FRA1/SOX10 Signaling.
AB  - UBE2N is a K63-specific ubiquitin conjugase linked to various immune disorders
      and cancer. Here, we demonstrate that UBE2N and its partners UBE2V1 and UBE2V2
      are highly expressed in malignant melanoma. Silencing of UBE2N and its partners
      significantly decreased melanoma cell proliferation and subcutaneous tumor
      growth. This was accompanied by increased expression of E-cadherin, p16, and MC1R
      and decreased expression of melanoma malignancy markers including SOX10, Nestin,
      and ABCB5. Mass spectrometry-based phosphoproteomic analysis revealed that UBE2N
      loss resulted in distinct alterations to the signaling landscape: MEK/ERK
      signaling was impaired, FRA1 and SOX10 gene regulators were downregulated, and
      p53 and p16 tumor suppressors were upregulated. Similar to inhibition of UBE2N
      and MEK, silencing FRA1 decreased SOX10 expression and cell proliferation.
      Conversely, exogenous expression of active FRA1 increased pMEK and SOX10
      expression, and restored anchorage-independent cell growth of cells with UBE2N
      loss. Systemic delivery of NSC697923, a small-molecule inhibitor of UBE2N,
      significantly decreased melanoma xenograft growth. These data indicate that UBE2N
      is a novel regulator of the MEK/FRA1/SOX10 signaling cascade and is indispensable
      for malignant melanoma growth. Our findings establish the basis for targeting
      UBE2N as a potential treatment strategy for melanoma.Significance: These findings
      identify ubiquitin conjugase UBE2N and its variant partners as novel regulators
      of MAPK signaling and potential therapeutic targets in melanoma. Cancer Res;
      78(22); 6462-72. (c)2018 AACR.

PMID- 30224377
TI  - Therapeutically Active RIG-I Agonist Induces Immunogenic Tumor Cell Killing in
      Breast Cancers.
AB  - Cancer immunotherapies that remove checkpoint restraints on adaptive immunity are
      gaining clinical momentum but have not achieved widespread success in breast
      cancers, a tumor type considered poorly immunogenic and which harbors a decreased
      presence of tumor-infiltrating lymphocytes. Approaches that activate innate
      immunity in breast cancer cells and the tumor microenvironment are of increasing
      interest, based on their ability to induce immunogenic tumor cell death, type I
      IFNs, and lymphocyte-recruiting chemokines. In agreement with reports in other
      cancers, we observe loss, downregulation, or mutation of the innate viral
      nucleotide sensor retinoic acid-inducible gene I (RIG-I/DDX58) in only 1% of
      clinical breast cancers, suggesting potentially widespread applicability for
      therapeutic RIG-I agonists that activate innate immunity. This was tested using
      an engineered RIG-I agonist in a breast cancer cell panel representing each of
      three major clinical breast cancer subtypes. Treatment with RIG-I agonist
      resulted in upregulation and mitochondrial localization of RIG-I and activation
      of proinflammatory transcription factors STAT1 and NF-kappaB. RIG-I agonist
      triggered the extrinsic apoptosis pathway and pyroptosis, a highly immunogenic
      form of cell death in breast cancer cells. RIG-I agonist also induced expression
      of lymphocyte-recruiting chemokines and type I IFN, confirming that cell death
      and cytokine modulation occur in a tumor cell-intrinsic manner. Importantly, RIG
      I activation in breast tumors increased tumor lymphocytes and decreased tumor
      growth and metastasis. Overall, these findings demonstrate successful therapeutic
      delivery of a synthetic RIG-I agonist to induce tumor cell killing and to
      modulate the tumor microenvironment in vivo Significance: These findings describe
      the first in vivo delivery of RIG-I mimetics to tumors, demonstrating a potent
      immunogenic and therapeutic effect in the context of otherwise poorly immunogenic
      breast cancers. Cancer Res; 78(21); 6183-95. (c)2018 AACR.

PMID- 30224378
TI  - Response to comment by Guerra et al.
AB  - This is a response by the authors of the review article 'A review of the
      multifunctionality of angiopoietin-like 4 in eye disease' [Biosci. Rep. (2018)
      38, BSR20180557, https://doi.org/10.1042/BSR20180557] to the comment published in
      this issue by Guerra et al. [Biosci. Rep. (2018) 38, BSR20180557,
      https://doi.org/10.1042/BSR20181462].

PMID- 30224379
TI  - Probiotics combined with aminosalicylic acid affiliates remission of ulcerative
      colitis: A meta-analysis of randomized controlled trial.
AB  - We conducted a meta-analysis to evaluate the effect of probiotic combined with
      aminosalicylic on induction remission maintenance treatment of ulcerative
      colitis. We conducted systematic searches in several Chinses and English
      databases from inception to June 2018, screening randomized controlled trial
      about effect of probiotics combined with aminosalicylic acid on ulcerative
      colitis. The evaluation indicator was the rate of remission. The relative risk
      (RR) and 95% confidence interval (CI) were calculated. A total of twenty-seven
      studies with 1942 patients were included. The results indicated that the
      remission rate was significantly higher in the group using probiotics combined
      with aminosalicylic acid than that in the group using aminosalicylic acid alone
      (RR=1.40, 95%CI: 1.27-1.53, P =0.000). The subgroup analysis indicated that
      probiotics combined with aminosalicylic acid can significantly elevate the
      remission rate in both mild to moderate (RR=1.33, 95%CI: 1.16-1.54, P =0.000) and
      active stage (RR=1.40, 95%CI: 1.27-1.64, P =0.000) ulcerative colitis. In
      different number of bacterium, drug types, treatment period, the combination with
      probiotics can significantly increase the remission rate ulcerative colitis. The
      funnel plot shown slight publication bias. Probiotics in conjunction with
      aminosalicylic can obviously increase the clinical remission rate of activity
      ulcerative colitis than drug alone. There was no significant difference between
      combined with mesalazine and salicylazosulfapyridine.

PMID- 30224382
TI  - MicroRNA therapy for infected wounds.

PMID- 30224381
TI  - In vivo generation of human CD19-CAR T cells results in B-cell depletion and
      signs of cytokine release syndrome.
AB  - Chimeric antigen receptor (CAR) T cells brought substantial benefit to patients
      with B-cell malignancies. Notwithstanding, CAR T-cell manufacturing requires
      complex procedures impeding the broad supply chain. Here, we provide evidence
      that human CD19-CAR T cells can be generated directly in vivo using the
      lentiviral vector CD8-LV specifically targeting human CD8+ cells. Administration
      into mice xenografted with Raji lymphoma cells and human peripheral blood
      mononuclear cells led to CAR expression solely in CD8+ T cells and efficacious
      elimination of CD19+ B cells. Further, upon injection of CD8-LV into mice
      transplanted with human CD34+ cells, induction of CAR T cells and CD19+ B-cell
      depletion was observed in 7 out of 10 treated animals. Notably, three mice showed
      elevated levels of human cytokines in plasma. Tissue-invading CAR T cells and
      complete elimination of the B-lymphocyte-rich zones in spleen were indicative of
      a cytokine release syndrome. Our data demonstrate the feasibility of in vivo
      reprogramming of human CD8+ CAR T cells active against CD19+ cells, yet with
      similar adverse effects currently notorious in the clinical practice.

PMID- 30224380
TI  - Non-coding RNA in drug resistance of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) has been one of the most highly lethal cancers.
      The acquisition of drug resistance accounts for the majority of poor effects of
      chemotherapy in HCC. Non-coding RNAs (ncRNAs) including miRNAs, long ncRNAs
      (lncRNAs), and circular RNA (circRNA) have been well-documented to participate in
      cancer occurrence and progression. Recently, multiple studies have highlighted
      the key roles of ncRNAs in chemoresistance of HCC. In addition, accumulating
      evidence has demonstrated that they can serve as biomarkers in diagnosis,
      treatment, and prognosis of HCC. In this review, we first overviewed up-to-date
      findings regarding miRNA and lncRNA in drug resistance of HCC, then summarized
      specific mechanisms that they modulate chemoresistance of HCC, and finally
      discussed their potential clinical application in overcoming the obstacle of HCC
      chemoresistance in the future.

PMID- 30224383
TI  - The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease.
AB  - The beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) initiates the
      generation of amyloid-beta (Abeta), and the amyloid cascade leading to amyloid
      plaque deposition, neurodegeneration, and dementia in Alzheimer's disease (AD).
      Clinical failures of anti-Abeta therapies in dementia stages suggest that
      treatment has to start in the early, asymptomatic disease states. The BACE-1
      inhibitor CNP520 has a selectivity, pharmacodynamics, and distribution profile
      suitable for AD prevention studies. CNP520 reduced brain and cerebrospinal fluid
      (CSF) Abeta in rats and dogs, and Abeta plaque deposition in APP-transgenic mice.
      Animal toxicology studies of CNP520 demonstrated sufficient safety margins, with
      no signs of hair depigmentation, retina degeneration, liver toxicity, or
      cardiovascular effects. In healthy adults >= 60 years old, treatment with CNP520
      was safe and well tolerated and resulted in robust and dose-dependent Abeta
      reduction in the cerebrospinal fluid. Thus, long-term, pivotal studies with
      CNP520 have been initiated in the Generation Program.

PMID- 30224386
TI  - USP38 critically promotes asthmatic pathogenesis by stabilizing JunB protein.
AB  - Th2 immune response is critical for allergic asthma pathogenesis. Molecular
      mechanisms for regulating Th2 immunity are still not well understood. Here we
      report that the ubiquitin-specific protease USP38 is crucial for Th2-mediated
      allergic asthma. TCR stimulation up-regulated the USP38 level, and USP38 in turn
      mediated the protein stabilization of JunB, a transcription factor specific for
      Th2 development. Consequently, USP38 was specifically required for TCR-induced
      production of Th2 cytokines and Th2 development both in vitro and in vivo, and
      USP38-deficient mice were resistant to asthma pathogenesis induced by OVA or HDM.
      Mechanistically, USP38 directly associated with JunB, deubiquitinated Lys-48
      linked poly-ubiquitination of JunB, and consequently blocked TCR-induced JunB
      turnover. USP38 represents the first identified deubiquitinase specifically for
      Th2 immunity and the associated asthma.

PMID- 30224387
TI  - Relation between illness representation and self-reported degree-of-worry in
      patients calling out-of-hours services: a mixed-methods study in Copenhagen,
      Denmark.
AB  - OBJECTIVES: To examine the relation between patients' illness representations,
      presented in telephone consultation to out-of-hours (OOH) services, and self
      reported degree-of-worry (DOW), as a measure of self-evaluated urgency. If a
      clear relation is found, incorporating DOW during telephone triage could aid the
      triage process, potentially increasing patient safety. DESIGN: A convergent
      parallel mixed methods design with quantitative data; DOW and qualitative data
      from recorded telephone consultations. Thematic analysis of the qualitative data
      was used to explore the content of the quantitatively scaled DOW, using the
      Common-Sense Model of Self-Regulation (CSM). SETTING: A convenience sampling of
      calls to the OOH services in Copenhagen, Denmark, during 3 days was included in
      the study. PARTICIPANTS: Calls from adults (>=15 years of age) concerning somatic
      illness during the data collection period were eligible for inclusion. Calls made
      on behalf of another person, calls concerning perceived life-threatening illness
      or calls regarding logistical/practical problems were excluded, resulting in
      analysis of 180 calls. RESULTS: All five components of the CSM framework,
      regardless of DOW, were present in the data. All callers referred to identity and
      timeline and were least likely to refer to consequence (37%). Through qualitative
      analysis, themes were defined. Callers with a strong identity, illness duration
      of less than 24 hours, clear cause and solution for cure/control seemed to
      present a lower DOW. Callers with a medium identity, illness duration of more
      than 24 hours and a high consequence seemed to present a higher DOW. CONCLUSION:
      This study suggests a relation between a patient's illness representation and
      self-evaluation of urgency. Incorporating a patient's DOW during telephone triage
      could aid the triage process in determining urgency and type of healthcare
      needed, potentially increasing patient safety. Research on patient outcome after
      DOW-assisted triage is needed before implementation of the DOW scale is
      recommended.

PMID- 30224385
TI  - The regulation of cilium assembly and disassembly in development and disease.
AB  - The primary cilium is an antenna-like organelle assembled on most types of
      quiescent and differentiated mammalian cells. This immotile structure is
      essential for interpreting extracellular signals that regulate growth,
      development and homeostasis. As such, ciliary defects produce a spectrum of human
      diseases, termed ciliopathies, and deregulation of this important organelle also
      plays key roles during tumor formation and progression. Recent studies have begun
      to clarify the key mechanisms that regulate ciliary assembly and disassembly in
      both normal and tumor cells, highlighting new possibilities for therapeutic
      intervention. Here, we review these exciting new findings, discussing the
      molecular factors involved in cilium formation and removal, the intrinsic and
      extrinsic control of cilium assembly and disassembly, and the relevance of these
      processes to mammalian cell growth and disease.

PMID- 30224388
TI  - Incidence of unintended pregnancy among female sex workers in low-income and
      middle-income countries: a systematic review and meta-analysis.
AB  - OBJECTIVES: To determine the incidence of unintended pregnancy among female sex
      workers (FSWs) in low-income and middle-income countries (LMICs). DESIGN: We
      searched MEDLINE, PsychInfo, Embase and Popline for papers published in English
      between January 2000 and January 2016, and Web of Science and Proquest for
      conference abstracts. Meta-analysis was performed on the primary outcomes using
      random effects models, with subgroup analysis used to explore heterogeneity.
      PARTICIPANTS: Eligible studies targeted FSWs aged 15-49 years living or working
      in an LMIC. OUTCOME MEASURES: Studies were eligible if they provided data on one
      of two primary outcomes: incidence of unintended pregnancy and incidence of
      pregnancy where intention is undefined. Secondary outcomes were also extracted
      when they were reported in included studies: incidence of induced abortion;
      incidence of birth; and correlates/predictors of pregnancy or unintended
      pregnancy. RESULTS: Twenty-five eligible studies were identified from 3866
      articles. Methodological quality was low overall. Unintended pregnancy incidence
      showed high heterogeneity (I2>95%), ranging from 7.2 to 59.6 per 100 person-years
      across 10 studies. Study design and duration were found to account for
      heterogeneity. On subgroup analysis, the three cohort studies in which no
      intervention was introduced had a pooled incidence of 27.1 per 100 person-years
      (95% CI 24.4 to 29.8; I2=0%). Incidence of pregnancy (intention undefined) was
      also highly heterogeneous, ranging from 2.0 to 23.4 per 100 person-years (15
      studies). CONCLUSIONS: Of the many studies examining FSWs' sexual and
      reproductive health in LMICs, very few measured pregnancy and fewer assessed
      pregnancy intention. Incidence varied widely, likely due to differences in study
      design, duration and baseline population risk, but was high in most studies,
      representing a considerable concern for this key population. Evidence-based
      approaches that place greater importance on unintended pregnancy prevention need
      to be incorporated into existing sexual and reproductive health programmes for
      FSWs. PROSPERO REGISTRATION NUMBER: CRD42016029185.

PMID- 30224389
TI  - Study protocol for a cohort study of patients with advanced heart failure in
      Singapore.
AB  - INTRODUCTIO: Understanding the symptom and health expenditure burden among
      patients with advanced congestive heart failure (CHF) and their family caregivers
      is essential to reform policy and practice needed to provide quality care to
      these patients at affordable prices. The proposed cohort study titled Singapore
      Cohort of Patients with Advanced Heart Failure aims to describe trajectories of
      quality of life among patients and their primary informal caregivers, quantify
      healthcare utilisation and expenditures, assess changes in patient and caregiver
      awareness of and preferences for knowing diagnostic and prognostic information,
      awareness and utilisation of palliative care services, preferences for treatments
      and decision making, perceived quality of care, self-care, caregiver
      psychological distress and caregiver burden. METHODS: This cohort study will
      recruit 250 patients with New York Heart Association Classification class III and
      IV CHF from inpatient wards at two public tertiary healthcare institutions in
      Singapore. Patients and their primary informal caregiver are being surveyed every
      4 months until patients' death; caregivers are followed until 8 weeks postpatient
      death. Medical and billing records of patients are obtained and merged with
      patients' survey data. ETHICS AND DISSEMINATION: The study has been approved by
      an ethics board. Results from the study will be disseminated through publications
      and presentations targeting researchers, policy makers and clinicians interested
      in understanding and improving care for patients with advanced CHF. TRIAL
      REGISTRATION NUMBER: NCT03089034.

PMID- 30224390
TI  - Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute
      coronary syndromes (LILACS): protocol and study rationale for a randomised,
      double-blind, placebo-controlled, phase I/II clinical trial.
AB  - INTRODUCTION: Inflammation and dysregulated immune responses play a crucial role
      in atherosclerosis, underlying ischaemic heart disease (IHD) and acute coronary
      syndromes (ACSs). Immune responses are also major determinants of the
      postischaemic injury in myocardial infarction. Regulatory T cells
      (CD4+CD25+FOXP3+; Treg) induce immune tolerance and preserve immune homeostasis.
      Recent in vivo studies suggested that low-dose interleukin-2 (IL-2) can increase
      Treg cell numbers. Aldesleukin is a human recombinant form of IL-2 that has been
      used therapeutically in several autoimmune diseases. However, its safety and
      efficacy is unknown in the setting of coronary artery disease. METHOD AND
      ANALYSIS: Low-dose interleukin-2 in patients with stable ischaemic heart disease
      and acute coronary syndromes is a single-centre, first-in-class, dose-escalation,
      two-part clinical trial. Patients with stable IHD (part A) and ACS (part B) will
      be randomised to receive either IL-2 (aldesleukin; dose range 0.3-3*106 IU) or
      placebo once daily, given subcutaneously, for five consecutive days. Part A will
      have five dose levels with five patients in each group. Group 1 will receive a
      dose of 0.3*106 IU, while the dose for the remaining four groups will be
      determined on completion of the preceding group. Part B will have four dose
      levels with eight patients in each group. The dose of the first group will be
      based on part A. Doses for each of the subsequent three groups will similarly be
      determined after completion of the previous group. The primary endpoint is safety
      and tolerability of aldesleukin and to determine the dose that increases mean
      circulating Treg levels by at least 75%. ETHICS AND DISSEMINATION: The study
      received a favourable opinion by the Greater Manchester Central Research Ethics
      Committee, UK (17/NW/0012). The results of this study will be reported through
      peer-reviewed journals, conference presentations and an internal organisational
      report. TRIAL REGISTRATION NUMBER: NCT03113773; Pre-results.

PMID- 30224391
TI  - Group cognitive remediation therapy for adults with obesity prior to behavioural
      weight loss treatment: study protocol for a randomised controlled superiority
      study (CRT study).
AB  - INTRODUCTION: Individuals with obesity show deficits in executive functioning
      which have been implicated in decreased weight loss outcome. Preliminary evidence
      suggests that cognitive remediation therapy (CRT) improves executive functioning
      and weight loss in obesity. However, confirmatory support, especially for pre
      weight loss use, is lacking. The CRT study aims at determining the efficacy of
      CRT versus no treatment control in patients with obesity before entering
      behavioural weight loss (BWL) treatment. It is hypothesised that individuals who
      receive CRT will show better weight loss outcome, improved executive functioning,
      greater weight loss-related behavioural changes and higher attendance of BWL
      treatment, 6 and 12 months after cessation of CRT. METHODS AND ANALYSIS: In a
      single-centre, assessor-blinded, randomised, two-armed parallel-group superiority
      trial, 260 adults with body mass index >=35.0 kg/m2 are centrally randomised to 8
      week group-based CRT versus no treatment, before entering BWL treatment. Primary
      outcome is the amount of weight loss (%) at 6-month follow-up, compared with pre
      treatment, derived from measured body weight. Secondary outcomes include
      improvement in executive functioning post-treatment and in weight loss-related
      behaviour, mental and physical health, and attendance to BWL treatment at 6-month
      and 12-month follow-up. Maintenance of weight loss at 12-month follow-up will be
      determined. Mixed model analyses based on intent-to-treat will be used to compare
      the CRT and control groups with respect to differences in weight change between
      pre-treatment and 6-month follow-up. Similar models will be used for analysing 12
      month follow-up data and secondary outcomes. Further analyses will include
      additional covariates to identify predictors of treatment outcome. ETHICS AND
      DISSEMINATION: The study was approved by the Ethical Committee of the University
      of Leipzig (256-15-13072015, version 'Final 1.0 from 28 May 2015). The study
      results will be disseminated through peer-reviewed publications. TRIAL
      REGISTRATION NUMBER: DRKS00009333; Pre-results.

PMID- 30224392
TI  - Trends in mental health service utilisation in immigrant youth in Ontario,
      Canada, 1996-2012: a population-based longitudinal cohort study.
AB  - OBJECTIVE: To describe trends in mental health service use of youth by
      immigration status and characteristics. DESIGN: Population-based longitudinal
      cohort study from 1996 to 2012 using linked health and administrative datasets.
      SETTING: Ontario, Canada. PARTICIPANTS: Youth 10-24 years, living in Ontario,
      Canada. EXPOSURE: The main exposure was immigration status (recent immigrants vs
      long-term residents). Secondary exposures were region of origin and refugee
      status. MAIN OUTCOME MEASURE: Mental health hospitalisations, emergency
      department (ED) visits and outpatient visits within consecutive 3-year time
      periods. Poisson regression models estimated rate ratios (RR). RESULTS: Over 2.5
      million person years per period were included. Rates of recent immigrant mental
      health service utilisation were at least 40% lower than long-term residents
      (p<0.0001).Mental health hospitalisation and ED visit rates increased in long
      term residents (hospitalisations, RR 1.09 (95% CI 1.08 to 1.09); ED visits, RR
      1.15 (1.14 to 1.15)) and recent immigrants (hospitalisations RR 1.05 (1.03 to
      1.07); ED visits, RR 1.08 (1.05 to 1.11)). Mental health outpatient visit rates
      increased in long-term residents (RR 1.03 (1.03 to 1.03)) but declined in recent
      immigrant (RR 0.94 (0.93 to 0.95)). Comparable divergent trends in acute care and
      outpatient service use were observed among refugees and across most regions of
      origin. Recent immigrant acute care use was driven by longer-term refugees
      (hospitalisations RR 1.12 (1.03 to 1.21); ED visits RR 1.11 (1.02 to 1.20)).
      CONCLUSIONS: Mental health service utilisation was lower among recent immigrants
      than long-term residents. While acute care use is increasing at a faster rate
      among long-term residents than recent immigrants, the decrease in outpatient
      mental health visits in immigrants highlights a potential emerging disparity in
      access to preventative care.

PMID- 30224393
TI  - Quantity of opioids consumed following an emergency department visit for acute
      pain: a Canadian prospective cohort study.
AB  - OBJECTIVES: Prescription opioid diversion is a significant contributor to the
      opioid misuse epidemic. We examined the quantity of opioids consumed by emergency
      department (ED) discharged patients after treatment for an acute pain condition
      (musculoskeletal, fracture, renal colic, abdominal pain and other), and the
      percentage of unused opioids available for potential misuse. DESIGN: Prospective
      cohort study. SETTING: Tertiary care trauma centre academic hospital.
      PARTICIPANTS: A convenience sample of patients >=18 years who visited the ED for
      an acute pain condition (<=2 weeks) and were discharged with an opioid
      prescription. Patients completed a 14-day paper diary of daily pain medication
      use. To reduce lost to follow-up, participants also responded to standardised
      phone interview questions about their previous 14-day pain medication use.
      OUTCOMES: Quantity of morphine 5 mg tablets (or equivalent) prescribed, consumed
      and unused during a 14-day follow-up. Quantity of opioids to adequately supply
      80% of patients for 2 weeks and 95% of patients for the first 3 days was also
      calculated. RESULTS: Results for 627 patients were analysed (mean age +/-SD: 51+/
      16 years, 48% women). Patients consumed a median of seven tablets of morphine 5
      mg (32% of the total prescribed opioids). The quantity of opioids to adequately
      supply 80% of patients for 2 weeks was 20 tablets of morphine 5 mg for
      musculoskeletal pain, 30 for fracture, 15 for renal colic or abdominal pain and
      20 for other pain conditions. The quantity to adequately supply 95% of patients
      for the first 3 days was 15 tablets of morphine 5 mg. CONCLUSIONS: Patients
      discharged from the ED with an acute pain condition consumed a median of fewer
      than 10 tablets of morphine 5 mg (or equivalent). ED physicians should consider
      prescribing a smaller quantity of opioids and asking the pharmacist to dispense
      them in portions to minimise unused opioids. TRIAL REGISTRATION NUMBER:
      NCT02799004; Results.

PMID- 30224394
TI  - Management of sepsis in out-of-hours primary care: a retrospective study of
      patients admitted to the intensive care unit.
AB  - OBJECTIVES: Timely recognition and treatment of sepsis is essential to reduce
      mortality and morbidity. Acutely ill patients often consult a general
      practitioner (GP) as the first healthcare provider. During out-of-hours, GP
      cooperatives deliver this care in the Netherlands. The aim of this study is to
      explore the role of these GP cooperatives in the care for patients with sepsis.
      DESIGN: Retrospective study of patient records from both the hospital and the GP
      cooperative. SETTING: An intensive care unit (ICU) of a general hospital in the
      Netherlands, and the colocated GP cooperative serving 260 000 inhabitants.
      PARTICIPANTS: We used data from 263 patients who were admitted to the ICU due to
      community-acquired sepsis between January 2011 and December 2015. MAIN OUTCOME
      MEASURES: Contact with the GP cooperative within 72 hours prior to hospital
      admission, type of contact, delay from the contact until hospital arrival, GP
      diagnosis, initial vital signs and laboratory values, and hospital mortality.
      RESULTS: Of 263 patients admitted to the ICU, 127 (48.3%) had prior GP
      cooperative contacts. These contacts concerned home visits (59.1%), clinic
      consultations (18.1%), direct ambulance deployment (12.6%) or telephone advice
      (10.2%). Patients assessed by a GP were referred in 64% after the first contact.
      The median delay to hospital arrival was 1.7 hours. The GP had not suspected an
      infection in 43% of the patients. In this group, the in-hospital mortality rate
      was significantly higher compared with patients with suspected infections (41.9%
      vs 17.6%). Mortality difference remained significant after correction for
      confounders. CONCLUSION: GP cooperatives play an important role in prehospital
      management of sepsis and recognition of sepsis in this setting proved difficult.
      Efforts to improve management of sepsis in out-of-hours primary care should not
      be limited to patients with a suspected infection, but also include severely ill
      patients without clear signs of infection.

PMID- 30224395
TI  - Classifying atopic dermatitis: protocol for a systematic review of subtypes
      (phenotypes) and associated characteristics.
AB  - INTRODUCTION: Atopic dermatitis is a complex disease with differing clinical
      presentations. Many attempts have been made to identify uniform subtypes, or
      phenotypes, of atopic dermatitis in order to identify different aetiologies,
      improve diagnosis, estimate more accurate clinical prognoses, inform treatment
      andmanagement or predict treatment efficacy andeffectiveness. However, no
      consensus yet exists on exactly what defines these phenotypes or how many there
      are and whether they are genuine or statistical artefacts. This review aims to
      identify previously reported phenotypes of atopic dermatitis, the features used
      to define them and any characteristics or clinical outcomes significantly
      associated with them. METHODS AND ANALYSIS: We will search Ovid Embase, Ovid
      MEDLINE and Web of Science from inception to the latest available date at the
      time of the search for studies attempting to classify atopic dermatitis in humans
      using any cross-sectional or longitudinal epidemiological or interventional
      design. Primary outcomes are atopic dermatitis phenotypes, features used to
      define them and characteristics associated with them in subsequent analyses. A
      secondary outcome is the methodological approach used to derive them. Two
      reviewers will independently screen titles and abstracts for inclusion, extract
      data and assess study quality. We will present the results of this review
      descriptively and with frequencies where possible. ETHICS AND DISSEMINATION:
      Ethical approval is not required for this study as it is a systematic review. We
      will report results from this systematic review in a peer-reviewed journal. The
      main value of this study will be to inform further research. PROSPERO
      REGISTRATION NUMBER: CRD42018087500.

PMID- 30224396
TI  - Policy addressing suicidality in children and young people: a scoping review
      protocol.
AB  - INTRODUCTION: Suicide is one of the leading causes of death among children and
      young people globally and a major public health issue. Government policies
      determine how much recognised health issues are prioritised and set the context
      for investment, development and delivery of services. A review of policies
      concerning children and young people who are suicidal could shed light on the
      extent that this public health issue is prioritised and highlight examples of
      best practice in this area. There has never been a review to explore how policy
      worldwide addresses the specific needs of this vulnerable population. This review
      will map the key policy documents and identify their relevance to the review
      question: how does policy address the treatment and care of children and young
      people who experience suicidality? (international, national (UK) and local
      (Scotland)). METHODOLOGY: Employing scoping review methodological guidance a
      systematic and transparent approach will be taken. Preliminary searches will
      facilitate the identification of MeSh terms, subject headings, individual
      database and platform nuances. A full search strategy will be created to search
      five databases: CINAHL, PsychInfo, Medline, Web of Science and Cochrane.
      Government and other key agency websites (eg, WHO, Unicef) will be searched to
      identify policy documents. The reference lists of identified documents will be
      checked. A second reviewer will independently screen and cross validate eligible
      studies for final inclusion. A data extraction template will then be used to
      extract key information. We will report our findings using narrative synthesis
      and tabulate findings, by agreed key components. ETHICS AND DISSEMINATION:
      Ethical approval is not required to conduct a scoping review. We will disseminate
      the findings through a peer-reviewed publication and conference presentation.

PMID- 30224384
TI  - Modulation of three key innate immune pathways for the most common retinal
      degenerative diseases.
AB  - This review highlights the role of three key immune pathways in the
      pathophysiology of major retinal degenerative diseases including diabetic
      retinopathy, age-related macular degeneration, and rare retinal dystrophies. We
      first discuss the mechanisms how loss of retinal homeostasis evokes an unbalanced
      retinal immune reaction involving responses of local microglia and recruited
      macrophages, activity of the alternative complement system, and inflammasome
      assembly in the retinal pigment epithelium. Presenting these key mechanisms as
      complementary targets, we specifically emphasize the concept of immunomodulation
      as potential treatment strategy to prevent or delay vision loss. Promising
      molecules are ligands for phagocyte receptors, specific inhibitors of complement
      activation products, and inflammasome inhibitors. We comprehensively summarize
      the scientific evidence for this strategy from preclinical animal models, human
      ocular tissue analyses, and clinical trials evolving in the last few years.

PMID- 30224397
TI  - Haemoglobin A1c and hearing impairment: longitudinal analysis using a large
      occupational health check-up data of Japan.
AB  - OBJECTIVES: The aim of this study was to determine whether haemoglobin A1c
      (HbA1c) level is associated with the incidence of hearing impairment accounting
      for smoking status and diabetic condition at baseline. METHODS: Participants were
      131 689 men and 71 286 women aged 30-65 years and free of hearing impairment at
      baseline (2008) who attended Japanese occupational annual health check-ups from
      2008 to 2015. We defined low-frequency hearing impairment at a hearing threshold
      >30 dB at 1 kHz and high frequency at >40 dB at 4 kHz in the better ear in pure
      tone audiometric tests. HbA1c was categorised into seven categories. The
      association between HbA1c and hearing impairment was assessed using the Cox
      proportional hazards model. RESULTS: On 5 years mean follow-up, high HbA1c was
      associated with high-frequency hearing impairment. In non-smokers, HbA1c>=8.0%
      was associated with high-frequency hearing impairment, with a multivariable HR
      (95% CI) compared with HbA1c 5.0%-5.4% of 1.46 (1.10 to 1.94) in men and 2.15
      (1.13 to 4.10) in women. There was no significant association between HbA1c and
      hearing impairment in smokers. A J-shaped association between HbA1c and high
      frequency hearing impairment was observed for participants with diabetes at
      baseline. HbA1c was not associated with low-frequency hearing impairment among
      any participants. CONCLUSIONS: HbA1c >=8.0% of non-smokers and >=7.3% of
      participants with diabetes was associated with high-frequency hearing impairment.
      These findings indicate that appropriate glycaemic control may prevent diabetic
      related hearing impairment.

PMID- 30224399
TI  - Essential fracture and orthopaedic equipment lists in low resource settings:
      consensus derived by survey of experts in Africa.
AB  - INTRODUCTION: Low/middle-income countries (LMICs) have a growing need for trauma
      and orthopaedic (T&O) surgical interventions but lack surgical resources. Part of
      this is due to the high amount of road traffic accidents in LMICs. We aimed to
      develop recommendations for an essential list of equipment for three different
      levels of care providers. METHODS: The Delphi method was used to achieve
      consensus on essential and desirable T&O equipment for LMICs. Twenty experts with
      T&O experience from LMICs underwent two rounds of questionnaires. Feedback was
      given after each round of questionnaires. The first round of questionnaire
      consisted of 45 items graded on a Likert scale with the second round consisting
      of 50 items. We used an electronic questionnaire to collect our data for three
      different levels of care: non-operative-based provider, specialist provider with
      operative fracture care and tertiary provider with operative fracture care and
      orthopaedics. RESULTS: After two rounds of questionnaires, recommendations for
      each level of care in LMICs included 4 essential equipment items for non
      operative-based providers; 27 essential equipment items for specialist providers
      with operative fracture care and 46 essential equipment items for tertiary
      providers with operative fracture care and orthopaedic care. CONCLUSION: These
      recommendations can facilitate in planning of appropriate equipment required in
      an institution which in turn has the potential to improve the capacity and
      quality of T&O care in LMICs. The essential equipment lists provided here can
      help direct where funding for equipment should be targeted. Our recommendations
      can help with planning and organising national T&O care in LMICs to achieve
      appropriate capacity at all relevant levels of care.

PMID- 30224400
TI  - Presenting a strong and united front to tobacco industry interference : a content
      analysis of Australian newspaper coverage of tobacco plain packaging 2008-2014.
AB  - OBJECTIVES: In 2012, Australia was the first country in the world to introduce
      plain or standardised tobacco packaging, coupled with larger graphic health
      warnings. This policy was fiercely opposed by industry. Media coverage can be an
      influential contributor to public debate, and both public health advocates and
      industry sought media coverage for their positions. The aim of this study was to
      measure the print media coverage of Australian's plain packaging laws, from
      inception to roll-out, in major Australian newspapers. METHODS: This study
      monitored mainstream Australian print media (17 newspapers) coverage of the plain
      packaging policy debate and implementation, over a 7-year period from January
      2008 to December 2014. Articles (n=701) were coded for article type, opinion
      slant and topic(s). DESIGN: Content analysis. RESULTS: Coverage of plain
      packaging was low during preimplementation phase (2008-2009), increasing sharply
      in the lead into legislative processes and diminished substantially after
      implementation. Articles covered policy rationale, policy progress and industry
      arguments. Of the news articles, 96% were neutrally framed. Of the editorials,
      55% were supportive, 28% were opposing, 12% were neutral and 5% were mixed.
      CONCLUSIONS: Protracted political debate, reflected in the media, led to an
      implementation delay of plain packaging. While Australian media provided
      comprehensive coverage of industry arguments, news coverage was largely neutral,
      whereas editorials were mostly supportive or neutral of the policy. Countries
      seeking to implement plain packaging of tobacco should not be deterred by the
      volume of news coverage, but should actively promote the evidence for plain
      packaging in the media to counteract the arguments of the tobacco industry.

PMID- 30224401
TI  - Future projection of the physician workforce and its geographical equity in
      Japan: a cohort-component model.
AB  - INTRODUCTION: The geographical inequity of physicians is a serious problem in
      Japan. However, there is little evidence of inequity in the future geographical
      distribution of physicians, even though the future physician supply at the
      national level has been estimated. In addition, possible changes in the age and
      sex distribution of future physicians are unclear. Thus, the purpose of this
      study is to project the future geographical distribution of physicians and their
      demographics. METHODS: We used a cohort-component model with the following
      assumptions: basic population, future mortality rate, future new registration
      rate, and future in-migration and out-migration rates. We examined changes in the
      number of physicians from 2005 to 2035 in secondary medical areas (SMAs) in
      Japan. To clarify the trends by regional characteristics, SMAs were divided into
      four groups based on urban or rural status and initial physician supply
      (lower/higher). The number of physicians was calculated separately by sex and age
      strata. RESULTS: From 2005 to 2035, the absolute number of physicians aged 25-64
      will decline by 6.1% in rural areas with an initially lower physician supply, but
      it will increase by 37.0% in urban areas with an initially lower supply. The
      proportion of aged physicians will increase in all areas, especially in rural
      ones with an initially lower supply, where it will change from 14.4% to 31.3%.
      The inequity in the geographical distribution of physicians will expand despite
      an increase in the number of physicians in rural areas. CONCLUSIONS: We found
      that the geographical disparity of physicians will worsen from 2005 to 2035.
      Furthermore, physicians aged 25-64 will be more concentrated in urban areas, and
      physicians will age more rapidly in rural places than urban ones. The regional
      disparity in the physician supply will worsen in the future if new and drastic
      measures are not taken.

PMID- 30224402
TI  - Neurocognitive and mental health outcomes and association with quality of life
      among adults living with HIV: a cross-sectional focus on a low-literacy
      population from coastal Kenya.
AB  - OBJECTIVES: Our aim was to compare the neurocognitive performance and mental
      health outcome of adults living with HIV on antiretroviral therapy with that of
      community controls, all of low literacy. Furthermore, we also wanted to explore
      the relationship of these outcomes with quality of life among adults living with
      HIV. STUDY DESIGN: This was a descriptive cross-sectional study. SETTING: The
      study was conducted in Kilifi County, a region located at the Kenyan coast.
      PARTICIPANTS: The participants consisted of a consecutive sample of 84 adults
      living with HIV and 83 randomly selected community controls all with <=8 years of
      schooling. All participants were assessed for non-verbal intelligence, verbal
      working memory and executive functioning. The Major Depression Inventory and a
      quality of life measure (RAND SF-36) were also administered. RESULTS: Using
      analysis of covariance, we found no statistically significant group differences
      between adults living with HIV and community controls in all the neurocognitive
      tests except for a marginal difference in the non-verbal intelligence test (F (1,
      158)=3.83, p=0.05). However, depressive scores of adults living with HIV were
      significantly higher than those of controls (F (1, 158)=11.56, p<0.01). Also,
      quality of life scores of adults living with HIV were significantly lower than
      those of controls (F (1, 158)=4.62, p=0.03). For the HIV-infected group, results
      from multivariable linear regression analysis showed that increasing depressive
      scores were significantly associated with poorer quality of life (beta=-1.17, 95%
      CI -1.55 to -0.80; p<0.01). CONCLUSION: Our findings suggest that adults of low
      literacy levels living with HIV and on antiretroviral medication at the Kenyan
      coast do not have significant cognitive deficits compared with their uninfected
      counterparts. However, their mental health, compared with that of HIV-uninfected
      adults, remains poorer and their quality of life may deteriorate when HIV and
      depressive symptoms co-occur.

PMID- 30224398
TI  - Cohort profile: Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre
      research collaboration.
AB  - PURPOSE: The ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration aims
      to address clinically relevant questions about safety and outcomes of intravenous
      thrombolysis (IVT) and endovascular thrombectomy. The findings can provide
      observational information on treatment of patients derived from everyday clinical
      practice. PARTICIPANTS: TRISP is an open, investigator-driven collaborative
      research initiative of European stroke centres with expertise in treatment with
      revascularisation therapies and maintenance of hospital-based registries. All
      participating centres made a commitment to prospectively collect data on
      consecutive patients with stroke treated with IVT using standardised definitions
      of variables and outcomes, to assure accuracy and completeness of the data and to
      adapt their local databases to answer novel research questions. FINDINGS TO DATE:
      Currently, TRISP comprises 18 centres and registers >10 000 IVT-treated patients.
      Prior TRISP projects provided evidence on the safety and functional outcome in
      relevant subgroups of patients who were excluded, under-represented or not
      specifically addressed in randomised controlled trials (ie, pre-existing
      disability, cervical artery dissections, stroke mimics, prior statin use),
      demonstrated deficits in organisation of acute stroke care (ie, IVT during non
      working hours, effects of onset-to-door time on onset-to-needle time), evaluated
      the association between laboratory findings on outcome after IVT and served to
      develop risk estimation tools for prediction of haemorrhagic complications and
      functional outcome after IVT. FUTURE PLANS: Further TRISP projects to increase
      knowledge of the effect and safety of revascularisation therapies in acute stroke
      are ongoing. TRISP welcomes participation and project proposals of further
      centres fulfilling the outlined requirements. In the future, TRISP will be
      extended to include patients undergoing endovascular thrombectomy.

PMID- 30224403
TI  - Evaluating the effect of income support policies on social health inequalities
      (SHIs) at birth in Montreal and Brussels using a contextualised comparative
      approach and model family method: a study protocol.
AB  - INTRODUCTION: Assessing the effects of social policies on social health
      inequalities (SHIs) is a complex issue. Variations in social policy between
      countries or regions provide natural experiments in policy implementation to
      perform comparative research. Comparisons are most enlightening when: the object
      of the evaluation is well defined (types of policies, population groups); the
      context of policy is analysed (history, implementation); the impact of policy on
      household poverty is outlined in detail; the influence of various factors (other
      than poverty) on SHI is taken into consideration. METHODS AND ANALYSIS: This
      study aims to understand how income support policies (ISPs) in Brussels and
      Montreal influence the poverty level of households receiving social assistance,
      and how they are associated with SHI at birth. Two cases studies will be carried
      out from a comparative perspective. The analysis includes four stages : (1) The
      model family method will be used to compare ISPs and their impact on disposable
      income and poverty of households receiving social assistance in both regions. (2)
      Statistical analysis of administrative databases will enable the description and
      comparison of SHI in adverse pregnancy outcomes across the two regions. (3)
      Analysis of databases and documents will allow for description of various factors
      which are likely to interact with poverty and influence SHI at birth. (4) Based
      on the Diderichsen model, results from the previous stages will be used to
      formulate hypotheses about the mechanisms by which ISPs contribute to increasing
      or reducing SHI at birth in both regions. ETHICS AND DISSEMINATION: This research
      was approved by the Human Research Ethics Committee for Health research of
      Universite de Montreal. In Belgium, the access to linked databases was approved
      by the Commission for the Protection of Privacy. Databases de-identified
      according to Belgian and Canadian legislation will be used. Results will be
      disseminated in scientific publications and will be shared with policy makers and
      field actors through collaborations with local organisations in Brussels and
      Montreal.

PMID- 30224405
TI  - Curricula and methods for physician compassion training: protocol for a
      systematic review.
AB  - INTRODUCTION: Compassionate patient care has been associated with improved
      clinical outcomes for patients. However, current evidence suggests that
      healthcare is experiencing a compassion crisis, with physicians frequently
      overlooking opportunities to treat patients with compassion. Although there is
      evidence that compassionate care can be enhanced through training interventions,
      it is currently unclear what specific skills and behaviours ought to be taught
      and how best to transfer this information to the learner. The objectives of this
      systematic review are to collate the world's literature on compassion training to
      determine (1) the specific skills and behaviours that should be taught
      (curriculum), and (2) the methods of training that are most effective at
      improving compassionate patient care. METHODS AND ANALYSIS: We will perform a
      qualitative systematic review of studies aimed at improving compassionate patient
      care among physicians and physicians in training. We will comprehensively search
      CENTRAL, MEDLINE, EMBASE and CINAHL. Additional recommended techniques for
      systematic reviews of complex evidence will be performed including pursuing
      selected 'references of references', electronic citation tracking and consulting
      experts in the field. Two investigators will independently review all search
      results. After identification and inclusion of papers, we will use a standardised
      form for data extraction. We will use tables to describe the study populations,
      interventions tested (including specific skill/behaviours taught and training
      methods used), outcome measures and effects of interventions on outcome measures
      compared with control groups. Where appropriate, meta-analysis will be used for
      quantitative analysis of the data. ETHICS AND DISSEMINATION: The proposed
      systematic review does not require ethical approval since no individual patient
      level data will be collected. Results of this study will contribute to the
      understanding of compassion training and help inform the development of
      compassion training curricula. PROSPERO REGISTRATION NUMBER: CRD42018095040.

PMID- 30224404
TI  - Atrial fibrillation detection using single lead portable electrocardiographic
      monitoring: a systematic review and meta-analysis.
AB  - OBJECTIVES: Recent technology advances have allowed for heart rhythm monitoring
      using single-lead ECG monitoring devices, which can be used for early diagnosis
      of atrial fibrillation (AF). We sought to investigate the AF detection rate using
      portable ECG devices compared with Holter monitoring. SETTING, PARTICIPANTS AND
      OUTCOME MEASURES: We searched the Medline, Embase and Scopus databases (conducted
      on 8 May 2017) using search terms related to AF screening and included studies
      with adults aged >18 years using portable ECG devices or Holter monitoring for AF
      detection. We excluded studies using implantable loop recorders and pacemakers.
      Using a random-effects model we calculated the overall AF detection rate. Meta
      regression analysis was performed to explore potential sources for heterogeneity.
      Quality of reporting was assessed using the tool developed by Downs and Black.
      RESULTS: Portable ECG monitoring was used in 18 studies (n=117 436) and Holter
      monitoring was used in 36 studies (n=8498). The AF detection rate using portable
      ECG monitoring was 1.7% (95% CI 1.4 to 2.1), with significant heterogeneity
      between studies (p<0.001). There was a moderate linear relationship between total
      monitoring time and AF detection rate (r=0.65, p=0.003), and meta-regression
      identified total monitoring time (p=0.005) and body mass index (p=0.01) as
      potential contributors to heterogeneity. The detection rate (4.8%, 95% CI 3.6% to
      6.0%) in eight studies (n=10 199), which performed multiple ECG recordings was
      comparable to that with 24 hours Holter (4.6%, 95% CI 3.5% to 5.7%). Intermittent
      recordings for 19 min total produced similar AF detection to 24 hours Holter
      monitoring. CONCLUSION: Portable ECG devices may offer an efficient screening
      option for AF compared with 24 hours Holter monitoring. PROSPERO REGISTRATION
      NUMBER: CRD42017061021.

PMID- 30224406
TI  - Neonatal palliative care: a practical checklist approach.
AB  - OBJECTIVES: Following publication of detailed national neonatal palliative care
      guidance, practical regional guidance, in the form of multidisciplinary
      'checklists', was implemented aiming to improve the quality of neonatal
      palliative care. METHODS: Case note audit was used to examine the quality of
      locally delivered neonatal palliative care before and after regional guidance
      implementation. RESULTS: 27 patients were allocated to the 'before' cohort and 10
      to the 'after' cohort. Introduction of the checklists was apparently associated
      with improvements in domains of pain relief and comfort care, monitoring, fluids
      and nutrition, completion of diagnostics, treatment ceiling decisions,
      resuscitation status and discussion with parents. Other support for parents was
      poorly adhered to. CONCLUSION: Regional guidance improved some aspects of
      palliative care delivery though other areas remained suboptimal. Other
      strategies, for example, consultation with paediatric palliative care services,
      need to be considered to further improve the quality of palliative care delivered
      to babies with life-limiting illnesses.

PMID- 30224407
TI  - Implementing bedside rounds to improve patient-centred outcomes: a systematic
      review.
AB  - BACKGROUND: Bedside rounds (BR) have been proposed as an ideal method to promote
      patient-centred hospital care, but there is substantial variation in their
      implementation and effects. Our objectives were to describe the implementation of
      BR in hospital settings and determine their effect on patient-centred outcomes.
      METHODS: Data sources included Ovid MEDLINE, Ovid Embase, Scopus and Ovid
      Cochrane Central Registry of Clinical Trials from database inception through 28
      July 2017. We included experimental studies comparing BR to another form of
      rounds in a hospital-based setting (ie, medical/surgical unit, intensive care
      unit (ICU)) and reporting a quantitative patient-reported or objectively measured
      clinical outcome. We used random effects models to calculate pooled Cohen's d
      effect size estimates for the patient knowledge and patient experience outcome
      domains. RESULTS: Twenty-nine studies met inclusion criteria, including 20 from
      adult care (17 non-ICU, 3 ICU), and nine from paediatrics (5 non-ICU, 4 ICU), the
      majority of which (n=23) were conducted in the USA. Thirteen studies implemented
      BR with cointerventions as part of a 'bundle'. Studies most commonly reported
      outcomes in the domains of patient experience (n=24) and patient knowledge
      (n=10). We found a small, statistically significant improvement in patient
      experience with BR (summary Cohen's d=0.09, 95% CI 0.04 to 0.14, p<0.001,
      I2=56%), but no significant association between BR and patient knowledge (Cohen's
      d=0.21, 95% CI -0.004 to -0.43, p=0.054, I2=92%). Risk of bias was moderate to
      high, with methodological limitations most often relating to selective reporting,
      low adherence rates and missing data. CONCLUSIONS: BR have been implemented in a
      variety of hospital settings, often 'bundled' with cointerventions. However, BR
      have demonstrated limited effect on patient-centred outcomes.

PMID- 30224408
TI  - Composite measures of healthcare quality: sensible in theory, problematic in
      practice.

PMID- 30224409
TI  - New therapies to relieve pain: The search for more efficient and safer
      alternatives to opioid pain killers.

PMID- 30224413
TI  - Five minutes with . . . Sophie Walker of the Women's Equality Party.

PMID- 30224411
TI  - The dual role of the centrosome in organizing the microtubule network in
      interphase.
AB  - Here, we address the regulation of microtubule nucleation during interphase by
      genetically ablating one, or two, of three major mammalian gamma-TuRC-binding
      factors namely pericentrin, CDK5Rap2, and AKAP450. Unexpectedly, we find that
      while all of them participate in microtubule nucleation at the Golgi apparatus,
      they only modestly contribute at the centrosome where CEP192 has a more
      predominant function. We also show that inhibiting microtubule nucleation at the
      Golgi does not affect centrosomal activity, whereas manipulating the number of
      centrosomes with centrinone modifies microtubule nucleation activity of the Golgi
      apparatus. In centrosome-free cells, inhibition of Golgi-based microtubule
      nucleation triggers pericentrin-dependent formation of cytoplasmic-nucleating
      structures. Further depletion of pericentrin under these conditions leads to the
      generation of individual microtubules in a gamma-tubulin-dependent manner. In all
      cases, a conspicuous MT network forms. Strikingly, centrosome loss increases
      microtubule number independently of where they were growing from. Our results
      lead to an unexpected view of the interphase centrosome that would control
      microtubule network organization not only by nucleating microtubules, but also by
      modulating the activity of alternative microtubule-organizing centers.

PMID- 30224412
TI  - Netrin-1/DCC-mediated PLCgamma1 activation is required for axon guidance and
      brain structure development.
AB  - Coordinated expression of guidance molecules and their signal transduction are
      critical for correct brain wiring. Previous studies have shown that phospholipase
      C gamma1 (PLCgamma1), a signal transducer of receptor tyrosine kinases, plays a
      specific role in the regulation of neuronal cell morphology and motility in vitro
      However, several questions remain regarding the extracellular stimulus that
      triggers PLCgamma1 signaling and the exact role PLCgamma1 plays in nervous system
      development. Here, we demonstrate that PLCgamma1 mediates axonal guidance through
      a netrin-1/deleted in colorectal cancer (DCC) complex. Netrin-1/DCC activates
      PLCgamma1 through Src kinase to induce actin cytoskeleton rearrangement. Neuronal
      progenitor-specific knockout of Plcg1 in mice causes axon guidance defects in the
      dorsal part of the mesencephalon during embryogenesis. Adult Plcg1-deficient mice
      exhibit structural alterations in the corpus callosum, substantia innominata, and
      olfactory tubercle. These results suggest that PLCgamma1 plays an important role
      in the correct development of white matter structure by mediating netrin-1/DCC
      signaling.

PMID- 30224414
TI  - Convexity of the moment map image for torus actions on bm -symplectic manifolds.
AB  - We prove a convexity theorem for the image of the moment map of a Hamiltonian
      torus action on a bm -symplectic manifold.This article is part of the theme issue
      'Finite dimensional integrable systems: new trends and methods'.

PMID- 30224415
TI  - Singular fibres of the Gelfand-Cetlin system on ??(n).
AB  - In this paper, we show that every singular fibre of the Gelfand-Cetlin system on
      co-adjoint orbits of unitary groups is a smooth isotropic submanifold which is
      diffeomorphic to a two-stage quotient of a compact Lie group by free actions of
      two other compact Lie groups. In many cases, these singular fibres can be shown
      to be homogeneous spaces or even diffeomorphic to compact Lie groups. We also
      give a combinatorial formula for computing the dimensions of all singular fibres,
      and give a detailed description of these singular fibres in many cases, including
      the so-called (multi-)diamond singularities. These (multi-)diamond singular
      fibres are degenerate for the Gelfand-Cetlin system, but they are Lagrangian
      submanifolds diffeomorphic to direct products of special unitary groups and tori.
      Our methods of study are based on different ideas involving complex ellipsoids,
      Lie groupoids and also general ideas coming from the theory of singularities of
      integrable Hamiltonian systems.This article is part of the theme issue 'Finite
      dimensional integrable systems: new trends and methods'.

PMID- 30224416
TI  - Symplectic invariants for parabolic orbits and cusp singularities of integrable
      systems.
AB  - We discuss normal forms and symplectic invariants of parabolic orbits and
      cuspidal tori in integrable Hamiltonian systems with two degrees of freedom. Such
      singularities appear in many integrable systems in geometry and mathematical
      physics and can be considered as the simplest example of degenerate
      singularities. We also suggest some new techniques which apparently can be used
      for studying symplectic invariants of degenerate singularities of more general
      type.This article is part of the theme issue 'Finite dimensional integrable
      systems: new trends and methods'.

PMID- 30224417
TI  - Dynamics of constrained many body problems in constant curvature two-dimensional
      manifolds.
AB  - In this paper, we investigate systems of several point masses moving in constant
      curvature two-dimensional manifolds and subjected to certain holonomic
      constraints. We show that in certain cases these systems can be considered as
      rigid bodies in Euclidean and pseudo-Euclidean three-dimensional spaces with
      points which can move along a curve fixed in the body. We derive the equations of
      motion which are Hamiltonian with respect to a certain degenerated Poisson
      bracket. Moreover, we have found several integrable cases of described models.
      For one of them, we give the necessary and sufficient conditions for the
      integrability.This article is part of the theme issue 'Finite dimensional
      integrable systems: new trends and methods'.

PMID- 30224418
TI  - Asymptotic velocity for four celestial bodies.
AB  - Asymptotic velocity is defined as the Cesaro limit of velocity. As such, its
      existence has been proved for bounded interaction potentials. This is known to be
      wrong in celestial mechanics with four or more bodies. Here, we show for a class
      of pair potentials including the homogeneous ones of degree -alpha for alpha?(0,
      2), that asymptotic velocities exist for up to four bodies, dimension three or
      larger, for any energy and almost all initial conditions on the energy
      surface.This article is part of the theme issue 'Finite dimensional integrable
      systems: new trends and methods'.

PMID- 30224419
TI  - Relations in the cohomology ring of the moduli space of flat SO(2n + 1)
      connections on a Riemann surface.
AB  - We consider the moduli space of flat SO(2n + 1)-connections (up to gauge
      transformations) on a Riemann surface, with fixed holonomy around a marked point.
      There are natural line bundles over this moduli space; we construct geometric
      representatives for the Chern classes of these line bundles, and prove that the
      ring generated by these Chern classes vanishes below the dimension of the moduli
      space, generalizing a conjecture of Newstead.This article is part of the theme
      issue 'Finite dimensional integrable systems: new trends and methods'.

PMID- 30224410
TI  - Translation acrobatics: how cancer cells exploit alternate modes of translational
      initiation.
AB  - Recent work has brought to light many different mechanisms of translation
      initiation that function in cells in parallel to canonical cap-dependent
      initiation. This has important implications for cancer. Canonical cap-dependent
      translation initiation is inhibited by many stresses such as hypoxia, nutrient
      limitation, proteotoxic stress, or genotoxic stress. Since cancer cells are often
      exposed to these stresses, they rely on alternate modes of translation initiation
      for protein synthesis and cell growth. Cancer mutations are now being identified
      in components of the translation machinery and in cis-regulatory elements of
      mRNAs, which both control translation of cancer-relevant genes. In this review,
      we provide an overview on the various modes of non-canonical translation
      initiation, such as leaky scanning, translation re-initiation, ribosome shunting,
      IRES-dependent translation, and m6A-dependent translation, and then discuss the
      influence of stress on these different modes of translation. Finally, we present
      examples of how these modes of translation are dysregulated in cancer cells,
      allowing them to grow, to proliferate, and to survive, thereby highlighting the
      importance of translational control in cancer.

PMID- 30224421
TI  - Open problems, questions and challenges in finite- dimensional integrable
      systems.
AB  - The paper surveys open problems and questions related to different aspects of
      integrable systems with finitely many degrees of freedom. Many of the open
      problems were suggested by the participants of the conference 'Finite-dimensional
      Integrable Systems, FDIS 2017' held at CRM, Barcelona in July 2017.This article
      is part of the theme issue 'Finite dimensional integrable systems: new trends and
      methods'.

PMID- 30224420
TI  - The U(n) Gelfand-Zeitlin system as a tropical limit of Ginzburg-Weinstein
      diffeomorphisms.
AB  - In this paper, we show that the Ginzburg-Weinstein diffeomorphism [Formula: see
      text] of Alekseev & Meinrenken (Alekseev, Meinrenken 2007 J. Differential
      Geom.76, 1-34. (10.4310/jdg/1180135664)) admits a scaling tropical limit on an
      open dense subset of [Formula: see text] The target of the limit map is a product
      [Formula: see text], where [Formula: see text] is the interior of a cone, T is a
      torus, and [Formula: see text] carries an integrable system with natural action
      angle coordinates. The pull-back of these coordinates to [Formula: see text]
      recovers the Gelfand-Zeitlin integrable system of Guillemin & Sternberg
      (Guillemin, Sternberg 1983 J. Funct. Anal.52, 106-128. (10.1016/0022
      1236(83)90092-7)). As a by-product of our proof, we show that the Lagrangian tori
      of the Flaschka-Ratiu integrable system on the set of upper triangular matrices
      meet the set of totally positive matrices for sufficiently large action
      coordinates.This article is part of the theme issue 'Finite dimensional
      integrable systems: new trends and methods'.

PMID- 30224422
TI  - A survey on polynomial in momenta integrals for billiard problems.
AB  - In this paper, we give a short survey of recent results on the algebraic version
      of the Birkhoff conjecture for integrable billiards on surfaces of constant
      curvature. We also discuss integrable magnetic billiards. As a new application of
      the algebraic technique, we study the existence of polynomial integrals for the
      two-sided magnetic billiards introduced by Kozlov and Polikarpov.This article is
      part of the theme issue 'Finite dimensional integrable systems: new trends and
      methods'.

PMID- 30224423
TI  - On the integrability of Birkhoff billiards.
AB  - In this survey, we provide a concise introduction to convex billiards and
      describe some recent results, obtained by the authors and collaborators, on the
      classification of integrable billiards, namely the so-called Birkhoff
      conjecture.This article is part of the theme issue 'Finite dimensional integrable
      systems: new trends and methods'.

PMID- 30224424
TI  - Gender neutral vaccination against HPV.

PMID- 30224425
TI  - Children's healthcare nurses should receive education in discussing intimate
      partner violence with new mothers.

PMID- 30224426
TI  - Failure is not an option - mitochondrial genome segregation in trypanosomes.
AB  - Unlike most other model eukaryotes, Trypanosoma brucei and its relatives have a
      single mitochondrion with a single-unit mitochondrial genome that is termed
      kinetoplast DNA (kDNA). Replication of the kDNA is coordinated with the cell
      cycle. During binary mitochondrial fission and prior to cytokinesis, the
      replicated kDNA has to be faithfully segregated to the daughter organelles. This
      process depends on the tripartite attachment complex (TAC) that physically links
      the kDNA across the two mitochondrial membranes with the basal body of the
      flagellum. Thus, the TAC couples segregation of the replicated kDNA with
      segregation of the basal bodies of the old and the new flagellum. In this Review,
      we provide an overview of the role of the TAC in kDNA inheritance in T. brucei We
      focus on recent advances regarding the molecular composition of the TAC, and
      discuss how the TAC is assembled and how its subunits are targeted to their
      respective TAC subdomains. Finally, we will contrast the segregation of the
      single-unit kDNA in trypanosomes to mitochondrial genome inheritance in yeast and
      mammals, both of which have numerous mitochondria that each contain multiple
      genomes.

PMID- 30224427
TI  - Cell scientist to watch - Serge Mostowy.
AB  - Serge Mostowy earned his bachelor degree in physics and master degree in
      evolutionary biology from McGill University, Montreal, Canada, where he then
      continued for his PhD in microbiology and immunology (focusing on Mycobacterium
      tuberculosis complex genomics) at the McGill Centre for the Study of Host
      Resistance under the supervision of Marcel Behr. Serge moved to the Institute
      Pasteur, Paris, France, for post-doctoral work with Pascale Cossart on the cell
      biology of infection. In 2012, he established his own research group as a
      Wellcome Trust Research Career Development Fellow in the Department of Medicine
      at Imperial College and was awarded the Lister Institute of Preventative Medicine
      Research Prize in 2015. In 2018, Serge was appointed as Professor at the London
      School of Hygiene & Tropical Medicine. He is the recipient of a Wellcome Trust
      Senior Research Fellowship and a European Research Council Consolidator Grant.
      The Mostowy laboratory is working on molecular mechanisms underlying bacterial
      infection and the role of the cytoskeleton in cellular immunity.

PMID- 30224428
TI  - First Person - Patrick Cunningham.
AB  - First Person is a series of interviews with the first authors of a selection of
      papers published in Journal of Cell Science, helping early-career researchers
      promote themselves alongside their papers. Patrick Cunningham is the first author
      on 'Neurodegeneration and locomotor dysfunction in Drosophila scarlet mutants',
      published in Journal of Cell Science. Patrick is a PhD student in the lab of
      Daniel T. Babcock at Lehigh University, Bethlehem, PA, investigating the loss of
      dopaminergic neurons in Drosophila in a model for Parkinson's disease.

PMID- 30224429
TI  - Correction: Disruption of Rab8a and Rab11a causes formation of basolateral
      microvilli in neonatal enteropathy (doi: 10.1242/jcs.201897).

PMID- 30224431
TI  - Sorafenib and Carfilzomib Synergistically Inhibit the Proliferation, Survival,
      and Metastasis of Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common and deadly human
      cancers. The 5-year survival rate is very low. Unfortunately, there are few
      efficacious therapeutic options. Until recently, Sorafenib has been the only
      available systemic drug for advanced HCC. However, it has very limited survival
      benefits, and new therapies are urgently needed. In this study, we investigated
      the anti-HCC activity of carfilzomib, a second-generation, irreversible
      proteasome inhibitor, as a single agent and in combination with sorafenib. In
      vitro, we found that carfilzomib has moderate anticancer activity toward liver
      cancer cells, but strongly enhances the ability of sorafenib to suppress HCC cell
      growth, proliferation, migration, invasion, and survival. Remarkably, the drug
      combination exhibits even more potent antitumor activity when tested in animal
      tumor models. Mechanistically, the combined treatment activates caspase-dependent
      and endoplasmic reticulum stress/CHOP-mediated apoptotic pathways, and suppresses
      epithelial-mesenchymal transition. In conclusion, our results demonstrate that
      the combination of carfilzomib and sorafenib has synergistic antitumor activities
      against HCC, providing a potential therapeutic strategy to improve the mortality
      and morbidity of HCC patients.

PMID- 30224430
TI  - Targeting Peroxisome Proliferator-Activated Receptor gamma to Increase Estrogen
      Induced Apoptosis in Estrogen-Deprived Breast Cancer Cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is an important
      transcription factor that modulates lipid metabolism and inflammation. However,
      it remains unclear whether PPARgamma is involved in modulation of estrogen (E2)
      induced inflammation, thus affecting apoptosis of E2-deprived breast cancer
      cells, MCF-7:5C and MCF-7:2A. Here, we demonstrated that E2 treatment suppressed
      the function of PPARgamma in both cell lines, although the suppressive effect in
      MCF-7:2A cells was delayed owing to high PPARgamma expression. Activation of
      PPARgamma by a specific agonist, pioglitazone, selectively blocked the induction
      of TNFalpha expression by E2, but did not affect other adipose inflammatory
      genes, such as fatty acid desaturase 1 and IL6. This suppression of TNFalpha
      expression by pioglitazone was mainly mediated by transrepression of nuclear
      factor-kappaB (NF-kappaB) DNA-binding activity. A novel finding was that NF
      kappaB functions as an oxidative stress inducer in MCF-7:5C cells but an
      antioxidant in MCF-7:2A cells. Therefore, the NF-kappaB inhibitor JSH-23
      displayed effects equivalent to those of pioglitazone, with complete inhibition
      of apoptosis in MCF-7:5C cells, but it increased E2-induced apoptosis in MCF-7:2A
      cells. Depletion of PPARgamma by siRNA or the PPARgamma antagonist T0070907
      accelerated E2-induced apoptosis, with activation of NF-kappaB-dependent TNFalpha
      and oxidative stress. For the first time, we demonstrated that PPARgamma is a
      growth signal and has potential to modulate NF-kappaB activity and oxidative
      stress in E2-deprived breast cancer cell lines. All of these findings suggest
      that anti-PPARgamma therapy is a novel strategy to improve the therapeutic
      effects of E2-induced apoptosis in E2-deprived breast cancer.

PMID- 30224432
TI  - A Trihelix Family Transcription Factor Is Associated with Key Genes in Mixed
      Linkage Glucan Accumulation.
AB  - Mixed-linkage glucan (MLG) is a polysaccharide that is highly abundant in grass
      endosperm cell walls and present at lower amounts in other tissues. Cellulose
      synthase-like F (CSLF) and cellulose synthase-like H genes synthesize MLG, but it
      is unknown if other genes participate in the production and restructuring of MLG.
      Using Brachypodium distachyon transcriptional profiling data, we identified a B
      distachyon trihelix family transcription factor (BdTHX1) that is highly
      coexpressed with the B distachyon CSLF6 gene (BdCSLF6), which suggests that
      BdTHX1 is involved in the regulation of MLG biosynthesis. To determine the genes
      regulated by this transcription factor, we conducted chromatin
      immunoprecipitation sequencing (ChIP-seq) experiments using immature B distachyon
      seeds and an anti-BdTHX1 polyclonal antibody. The ChIP-seq experiment identified
      the second intron of BdCSLF6 as one of the most enriched sequences. The binding
      of BdTHX1 to the BdCSLF6 intron sequence was confirmed using electrophoretic
      mobility shift assays (EMSA). ChIP-seq also showed that a gene encoding a grass
      specific glycoside hydrolase family 16 endotransglucosylase/hydrolase (BdXTH8) is
      bound by BdTHX1, and the binding was confirmed by EMSA. Radiochemical
      transglucanase assays showed that BdXTH8 exhibits predominantly MLG:xyloglucan
      endotransglucosylase activity, a hetero-transglycosylation reaction, and can thus
      produce MLG-xyloglucan covalent bonds; it also has a lower xyloglucan:xyloglucan
      endotransglucosylase activity. B distachyon shoots regenerated from transformed
      calli overexpressing BdTHX1 showed an abnormal arrangement of vascular tissue and
      seedling-lethal phenotypes. These results indicate that the transcription factor
      BdTHX1 likely plays an important role in MLG biosynthesis and restructuring by
      regulating the expression of BdCSLF6 and BdXTH8.

PMID- 30224435
TI  - Making and breaking of an essential poison: the cyclases and phosphodiesterases
      that produce and degrade the essential second messenger cyclic di-AMP in
      bacteria.
AB  - Cyclic di-AMP is a second messenger nucleotide that is produced by many bacteria
      and some archaea. Recent work has shown that c-di-AMP is unique among the
      signaling nucleotides, as this molecule is in many bacteria both essential on one
      hand and toxic upon accumulation on the other. Moreover, in bacteria like
      Bacillus subtilis, c-di-AMP controls a biological process, potassium homeostasis,
      by binding both potassium transporters and riboswitch molecules in the mRNAs that
      encode the potassium transporters. In addition to the control of potassium
      homeostasis, c-di-AMP has been implicated in many cellular activities including
      DNA repair, cell wall homeostasis, osmotic adaptation, biofilm formation, central
      metabolism, and virulence. C-di-AMP is synthesized and degraded by diadenylate
      cyclases and phosphodiesterases, respectively. In the diadenylate cyclases, one
      type of catalytic domain, the DAC domain, is coupled to various other domains
      that control the localization, the protein-protein interactions, and the
      regulation of the enzymes. The phosphodiesterases have a catalytic core that
      consists either of a DHH/DHHA1 or of a HD domain. Recent findings on the
      occurrence, domain organization, activity control and structural features of
      diadenylate cyclases and phosphodiesterases are discussed in this review.

PMID- 30224436
TI  - Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion in
      Chlamydia trachomatis and Can Reverse Cassette-Induced Polar Effects.
AB  - As obligate intracellular bacteria, Chlamydia spp. have evolved numerous, likely
      intricate, mechanisms to create and maintain a privileged intracellular niche.
      Recent progress in elucidating and characterizing these processes has been
      bolstered by the development of techniques enabling basic genetic tractability.
      Florescence-reported allelic exchange mutagenesis (FRAEM) couples chromosomal
      gene deletion with the insertion of a selection cassette encoding antibiotic
      resistance and green fluorescent protein (GFP). Similar to other bacteria, many
      chlamydial genes exist within polycistronic operons, raising the possibility of
      polar effects mediated by insertion cassettes. Indeed, FRAEM-mediated deletion of
      Chlamydia trachomatis tmeA negatively impacts the expression of tmeB We have
      adapted FRAEM technology by employing a gfp-bla cassette flanked by loxP sites.
      Conditional expression of Cre recombinase in Chlamydia tmeA containing a floxed
      cassette resulted in deletion of the marker and restoration of tmeB
      expression.IMPORTANCE C. trachomatis infections represent a significant burden to
      human health. The ability to genetically manipulate Chlamydia spp. is overcoming
      historic confounding barriers that have impeded rapid progress in understanding
      overall chlamydial pathogenesis. The current state of genetic manipulation in
      Chlamydia spp. requires further development, including mechanisms to generate
      markerless gene disruption. We leveraged a stepwise Cre-lox approach to excise
      selection marker genes from a deleted gene locus. We found this process to be
      efficient, and the removal of extraneous elements resulted in the reversal of a
      negative polar effect on a downstream gene. This technique facilitates a more
      direct assessment of gene function and adds to the Chlamydia molecular toolbox by
      facilitating the deletion of genes within operons.

PMID- 30224433
TI  - Timing and Order of the Molecular Events Marking the Onset of Berry Ripening in
      Grapevine.
AB  - Grapevine (Vitis vinifera) is a model for the investigation of physiological and
      biochemical changes during the formation and ripening of nonclimacteric fleshy
      fruits. However, the order and complexity of the molecular events during fruit
      development remain poorly understood. To identify the key molecular events
      controlling berry formation and ripening, we created a highly detailed
      transcriptomic and metabolomic map of berry development, based on samples
      collected every week from fruit set to maturity in two grapevine genotypes for
      three consecutive years, resulting in 219 samples. Major transcriptomic changes
      were represented by coordinated waves of gene expression associated with early
      development, veraison (onset of ripening)/midripening, and late-ripening and were
      consistent across vintages. The two genotypes were clearly distinguished by
      metabolite profiles and transcriptional changes occurring primarily at the
      veraison/midripening phase. Coexpression analysis identified a core network of
      transcripts as well as variations in the within-module connections representing
      varietal differences. By focusing on transcriptome rearrangements close to
      veraison, we identified two rapid and successive shared transitions involving
      genes whose expression profiles precisely locate the timing of the molecular
      reprogramming of berry development. Functional analyses of two transcription
      factors, markers of the first transition, suggested that they participate in a
      hierarchical cascade of gene activation at the onset of ripening. This study
      defined the initial transcriptional events that mark and trigger the onset of
      ripening and the molecular network that characterizes the whole process of berry
      development, providing a framework to model fruit development and maturation in
      grapevine.

PMID- 30224437
TI  - Genomic Sequencing of High-Efficiency Transducing Streptococcal Bacteriophage
      A25: Consequences of Escape from Lysogeny.
AB  - Lytic bacteriophage A25, which infects Streptococcus pyogenes and several related
      species, has been used to better understand phage-microbe interactions due to its
      ability to mediate high-efficiency transduction. Most of these studies, however,
      are decades old and were conducted prior to the advent of next-generation
      sequencing and bioinformatics. The aim of our study was to gain a better
      understanding of the mechanism of high-efficiency transduction through analysis
      of the A25 genome. We show here that phage A25 is related to a family of genome
      prophages and became a lytic phage following escape from lysogeny. A lambdoid
      like residual lysogeny module consisting of an operator site with two promoters
      and a cro-like antirepressor gene was identified, but the genes for the cI-like
      repressor and integrase are missing. Additionally, the genetic organization of
      the A25 genome was found to be modular in nature and similar to that of many
      prophages of S. pyogenes as well as from other streptococcal species. A study of
      A25 homology to all annotated prophages within S. pyogenes revealed near identity
      within the remnant lysogeny module of the A25 phage genome to the corresponding
      regions in resident prophages of genome strains MGAS10270 (M2), MGAS315 (M3),
      MGAS10570 (M4), and STAB902 (M4). Host range studies of MGAS10270, MGAS315, and
      MGAS10750 demonstrated that these strains were resistant to A25 infection. The
      resistance mechanism of superinfection immunity was confirmed experimentally
      through complementation of the operator region and cI-like repressor from
      prophage MGAS10270.2 into susceptible strains SF370, CEM1Delta4
      (SF370DeltaSpyCIM1), and ATCC 12204, which rendered all three strains resistant
      to A25 infection. In silico prediction of packaging through homology analysis of
      the terminase large subunit from bacteriophages within the known packaging
      mechanism of Gram-positive bacteria as well as the evidence of terminally
      redundant and/or circularly permuted sequences suggested that A25 grouped with
      phages employing the less stringent pac-type packaging mechanisms, which likely
      explains the characteristic A25 high-efficiency transduction capabilities. Only a
      few examples of lytic phages appearing following loss of part or all of the
      lysogeny module have been reported previously, and the genetic mosaicism of A25
      suggests that this event may not have been a recent one. However, the discovery
      that this lytic bacteriophage shares some of the genetic pool of S. pyogenes
      prophages emphasizes the importance of genetic and biological characterization of
      bacteriophages when selecting phages for therapeutics or disinfectants, as phage
      phage and phage-microbe interactions can be complex, requiring more than just
      assessment of host range and carriage of toxoid or virulence genes.IMPORTANCE
      Bacteriophages (bacterial viruses) play an important role in the shaping of
      bacterial populations as well as the dissemination of bacterial genetic material
      to new strains, resulting in the spread of virulence factors and antibiotic
      resistance genes. This study identified the genetic origins of Streptococcus
      pyogenes phage A25 and uncovered the molecular mechanism employed to promote
      horizontal transfer of DNA by transduction to new strains of this bacterium as
      well as identified the basis for its host range.

PMID- 30224438
TI  - Surfing Motility: a Conserved yet Diverse Adaptation among Motile Bacteria.
AB  - Bacterial rapid surfing motility is a novel surface adaptation of Pseudomonas
      aeruginosa in the presence of the glycoprotein mucin. Here, we show that other
      Gram-negative motile bacterial species, including Escherichia coli, Salmonella
      enterica, Vibrio harveyi, Enterobacter cloacae, and Proteus mirabilis, also
      exhibit the physical characteristics of surfing on the surface of agar plates
      containing 0.4% mucin, where surfing motility was generally more rapid and less
      dependent on medium viscosity than was swimming motility. As previously observed
      in Pseudomonas aeruginosa, all surfing species exhibited some level of broad
      spectrum adaptive resistance, although the antibiotics to which they demonstrated
      surfing-mediated resistance differed. Surfing motility in P. aeruginosa was found
      to be dependent on the quorum-sensing systems of this organism; however, this
      aspect was not conserved in other tested bacterial species, including V. harveyi
      and S. enterica, as demonstrated by assaying specific quorum-sensing mutants.
      Thus, rapid surfing motility is a complex surface growth adaptation that is
      conserved in several motile bacteria, involves flagella, and leads to diverse
      broad-spectrum antibiotic resistance, but it is distinct in terms of dependence
      on quorum sensing.IMPORTANCE This study showed for the first time that surfing
      motility, a novel form of surface motility first discovered in Pseudomonas
      aeruginosa under artificial cystic fibrosis conditions, including the presence of
      high mucin content, is conserved in other motile bacterial species known to be
      mucosa-associated, including Escherichia coli, Salmonella enterica, and Proteus
      mirabilis Here, we demonstrated that key characteristics of surfing, including
      the ability to adapt to various viscous environments and multidrug adaptive
      resistance, are also conserved. Using mutagenesis assays, we also identified the
      importance of all three known quorum-sensing systems, Las, Rhl, and Pqs, in P.
      aeruginosa in regulating surfing motility, and we also observed a conserved
      dependence of surfing on flagella in certain species.

PMID- 30224440
TI  - Reducing injudicious use of liver function tests.

PMID- 30224439
TI  - Modulation of CrbS-dependent activation of the acetate switch in Vibrio cholerae.
AB  - Vibrio cholerae controls the pathogenicity of interactions with arthropod hosts
      via the activity of the CrbS/R two component system. This signaling pathway
      regulates the consumption of acetate, which in turn, alters the relative
      virulence of interactions with arthropods, including Drosophila melanogaster CrbS
      is a histidine kinase that links a transporter-like domain to its signaling
      apparatus via putative STAC and PAS domains. CrbS and its cognate response
      regulator are required for expression of acetyl-CoA synthetase (acs), which
      converts acetate to acetyl-CoA. We demonstrate that the STAC domain of CrbS is
      required for signaling in culture; without it, acs transcription is reduced in LB
      medium, and V. cholerae cannot grow on acetate minimal media. However, the strain
      remains virulent towards Drosophila and expresses acs similarly to wild-type
      during infection. This suggests that there exists a unique signal or
      environmental variable that modulates CrbS in the gastrointestinal tract of
      Drosophila. Secondly, we present evidence in support of CrbR, the response
      regulator that interacts with CrbS, binding directly to the acs promoter, and we
      identify a region of the promoter that CrbR may target. We further demonstrate
      that nutrient signals, together with the CRP-cAMP system, control acs
      transcription, but regulation may occur indirectly, as CRP-cAMP activates
      expression of the crbS and crbR genes. Lastly, we define the role of the Pta-AckA
      system in V. cholerae, and identify redundancy built into acetate excretion
      pathways in this pathogen.Importance CrbS is a member of a unique family of
      sensor histidine kinases, as its structure suggests that it may link signaling to
      transport of a molecule. However, mechanisms through which CrbS senses and
      communicates information about the outside world are unknown. In the
      Vibrionaceae, orthologs of CrbS regulate acetate metabolism, which can, in turn,
      affect interactions with host organisms. Here, we situate CrbS within a larger
      regulatory framework, demonstrating that crbS is regulated by nutrient sensing
      systems. Furthermore, CrbS domains may play varying roles in signaling during
      infection and growth in culture, suggesting a unique mechanism of host
      recognition. Lastly, we define the roles of additional pathways in acetate flux,
      as a foundation for further studies of this metabolic nexus point.

PMID- 30224441
TI  - Are household disinfectants microbially mediated obesogens?

PMID- 30224443
TI  - Brucella infection at cardiac pacemaker site in a patient who had consumed raw
      caribou meat in Northern Canada.

PMID- 30224444
TI  - Emphysematous liver abscess in a 58-year-old woman.

PMID- 30224442
TI  - Postnatal exposure to household disinfectants, infant gut microbiota and
      subsequent risk of overweight in children.
AB  - BACKGROUND: Emerging links between household cleaning products and childhood
      overweight may involve the gut microbiome. We determined mediating effects of
      infant gut microbiota on associations between home use of cleaning products and
      future overweight. METHODS: From the Canadian Healthy Infant Longitudinal
      Development (CHILD) birth cohort, we tested associations between maternal report
      of cleaning product use and overweight at age 3, and whether associations were
      mediated by microbial profiles of fecal samples in 3- to 4-month-old infants.
      RESULTS: Among 757 infants, the abundance of specific gut microbiota was
      associated with household cleaning with disinfectants and eco-friendly products
      in a dose-dependent manner. With more frequent use of disinfectants,
      Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of
      use: adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.08 to 3.45)
      while genus Haemophilus declined in abundance (highest v. lowest quintile of use:
      AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted
      with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74).
      Lachnospiraceae abundance significantly mediated associations of the top 30th
      centile of household disinfectant use with higher body mass index (BMI) z score
      (p = 0.02) and with increased odds of overweight or obesity (p = 0.04) at age 3.
      Use of eco-friendly products was associated with decreased odds of overweight or
      obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to
      0.86), with no significant mediation (p = 0.2). INTERPRETATION: Exposure to
      household disinfectants was associated with higher BMI at age 3, mediated by gut
      microbial composition at age 3-4 months. Although child overweight was less
      common in households that cleaned with eco-friendly products, the lack of
      mediation by infant gut microbiota suggests another pathway for this association.

PMID- 30224445
TI  - Canadian program directors lack data to select residency candidates.

PMID- 30224446
TI  - Principles for screening: Too few concerns for informed consent and shared
      decision-making?

PMID- 30224447
TI  - Incoming CMA president seeks balance for a divided medical profession.

PMID- 30224448
TI  - Doctors on their own when dealing with racism from patients.

PMID- 30224449
TI  - Saudi medical trainees may keep posts in Canada.

PMID- 30224450
TI  - Chance of a Hearing Aid.

PMID- 30224451
TI  - IL-33 promotes recovery from acute colitis by inducing miR-320 to stimulate
      epithelial restitution and repair.
AB  - Defective and/or delayed wound healing has been implicated in the pathogenesis of
      several chronic inflammatory disorders, including inflammatory bowel disease
      (IBD). The resolution of inflammation is particularly important in mucosal
      organs, such as the gut, where restoration of epithelial barrier function is
      critical to reestablish homeostasis with the interfacing microenvironment.
      Although IL-33 and its receptor ST2/ILRL1 are known to be increased and
      associated with IBD, studies using animal models of colitis to address the
      mechanism have yielded ambiguous results, suggesting both pathogenic and
      protective functions. Unlike those previously published studies, we focused on
      the functional role of IL-33/ST2 during an extended (2-wk) recovery period after
      initial challenge in dextran sodium sulfate (DSS)-induced colitic mice. Our
      results show that during acute, resolving colitis the normal function of
      endogenous IL-33 is protection, and the lack of either IL-33 or ST2 impedes the
      overall recovery process, while exogenous IL-33 administration during recovery
      dramatically accelerates epithelial restitution and repair, with concomitant
      improvement of colonic inflammation. Mechanistically, we show that IL-33
      stimulates the expression of a network of microRNAs (miRs) in the Caco2 colonic
      intestinal epithelial cell (IEC) line, especially miR-320, which is increased by
      >16-fold in IECs isolated from IL-33-treated vs. vehicle-treated DSS colitic
      mice. Finally, IL-33-dependent in vitro proliferation and wound closure of Caco-2
      IECs is significantly abrogated after specific inhibition of miR-320A. Together,
      our data indicate that during acute, resolving colitis, IL-33/ST2 plays a crucial
      role in gut mucosal healing by inducing epithelial-derived miR-320 that promotes
      epithelial repair/restitution and the resolution of inflammation.

PMID- 30224452
TI  - Hippocampal CA1 gamma power predicts the precision of spatial memory judgments.
AB  - The hippocampus plays a critical role in spatial memory. However, the exact
      neural mechanisms underlying high-fidelity spatial memory representations are
      unknown. We report findings from presurgical epilepsy patients with bilateral
      hippocampal depth electrodes performing an object-location memory task that
      provided a broad range of spatial memory precision. During encoding, patients
      were shown a series of objects along the circumference of an invisible circle. At
      test, the same objects were shown at the top of the circle (0 degrees ), and
      patients used a dial to move the object to its location shown during encoding.
      Angular error between the correct location and the indicated location was
      recorded as a continuous measure of performance. By registering pre- and
      postimplantation MRI scans, we were able to localize the electrodes to specific
      hippocampal subfields. We found a correlation between increased gamma power,
      thought to reflect local excitatory activity, and the precision of spatial memory
      retrieval in hippocampal CA1 electrodes. Additionally, we found a similar
      relationship between gamma power and memory precision in the dorsolateral
      prefrontal cortex and a directional relationship between activity in this region
      and in the CA1, suggesting that the dorsolateral prefrontal cortex is involved in
      postretrieval processing. These results indicate that local processing in
      hippocampal CA1 and dorsolateral prefrontal cortex supports high-fidelity spatial
      memory representations.

PMID- 30224453
TI  - Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner
      subunit Ada2.
AB  - The Gcn5 histone acetyltransferase (HAT) subunit of the SAGA transcriptional
      coactivator complex catalyzes acetylation of histone H3 and H2B N-terminal tails,
      posttranslational modifications associated with gene activation. Binding of the
      SAGA subunit partner Ada2 to Gcn5 activates Gcn5's intrinsically weak HAT
      activity on histone proteins, but the mechanism for this activation by the Ada2
      SANT domain has remained elusive. We have employed Fab antibody fragments as
      crystallization chaperones to determine crystal structures of a yeast Ada2/Gcn5
      complex. Our structural and biochemical results indicate that the Ada2 SANT
      domain does not activate Gcn5's activity by directly affecting histone peptide
      binding as previously proposed. Instead, the Ada2 SANT domain enhances Gcn5
      binding of the enzymatic cosubstrate acetyl-CoA. This finding suggests a
      mechanism for regulating chromatin modification enzyme activity: controlling
      binding of the modification cosubstrate instead of the histone substrate.

PMID- 30224454
TI  - Behavior of homing endonuclease gene drives targeting genes required for
      viability or female fertility with multiplexed guide RNAs.
AB  - A gene drive method of particular interest for population suppression utilizes
      homing endonuclease genes (HEGs), wherein a site-specific, nuclease-encoding
      cassette is copied, in the germline, into a target gene whose loss of function
      results in loss of viability or fertility in homozygous, but not heterozygous,
      progeny. Earlier work in Drosophila and mosquitoes utilized HEGs consisting of
      Cas9 and a single guide RNA (gRNA) that together target a specific gene for
      cleavage. Homing was observed, but resistant alleles immune to cleavage, while
      retaining wild-type gene function, were also created through nonhomologous end
      joining. Such alleles prevent drive and population suppression. Targeting a gene
      for cleavage at multiple positions has been suggested as a strategy to prevent
      the appearance of resistant alleles. To test this hypothesis, we generated two
      suppression HEGs in Drosophila melanogaster targeting genes required for
      embryonic viability or fertility, using a HEG consisting of CRISPR/Cas9 and gRNAs
      designed to cleave each gene at four positions. Rates of target locus cleavage
      were very high, and multiplexing of gRNAs prevented resistant allele formation.
      However, germline homing rates were modest, and the HEG cassette was unstable
      during homing events, resulting in frequent partial copying of HEGs that lacked
      gRNAs, a dominant marker gene, or Cas9. Finally, in drive experiments, the HEGs
      failed to spread due to the high fitness load induced in offspring as a result of
      maternal carryover of Cas9/gRNA complex activity. Alternative design principles
      are proposed that may mitigate these problems in future gene drive engineering.

PMID- 30224455
TI  - Effects of protein size, thermodynamic stability, and net charge on
      cotranslational folding on the ribosome.
AB  - During the last five decades, studies of protein folding in dilute buffer
      solutions have produced a rich picture of this complex process. In the cell,
      however, proteins can start to fold while still attached to the ribosome
      (cotranslational folding) and it is not yet clear how the ribosome affects the
      folding of protein domains of different sizes, thermodynamic stabilities, and net
      charges. Here, by using arrest peptides as force sensors and on-ribosome pulse
      proteolysis, we provide a comprehensive picture of how the distance from the
      peptidyl transferase center in the ribosome at which proteins fold correlates
      with protein size. Moreover, an analysis of a large collection of mutants of the
      Escherichia coli ribosomal protein S6 shows that the force exerted on the nascent
      chain by protein folding varies linearly with the thermodynamic stability of the
      folded state, and that the ribosome environment disfavors folding of domains of
      high net-negative charge.

PMID- 30224456
TI  - Collimated ultrabright gamma rays from electron wiggling along a petawatt laser
      irradiated wire in the QED regime.
AB  - Even though high-quality X- and gamma rays with photon energy below mega-electron
      volt (MeV) are available from large-scale X-ray free electron lasers and
      synchrotron radiation facilities, it remains a great challenge to generate bright
      gamma rays over 10 MeV. Recently, gamma rays with energies up to the MeV level
      were observed in Compton scattering experiments based on laser wakefield
      accelerators, but the yield efficiency was as low as [Formula: see text], owing
      to low charge of the electron beam. Here, we propose a scheme to efficiently
      generate gamma rays of hundreds of MeV from submicrometer wires irradiated by
      petawatt lasers, where electron accelerating and wiggling are achieved
      simultaneously. The wiggling is caused by the quasistatic electric and magnetic
      fields induced around the wire surface, and these are so high that even quantum
      electrodynamics (QED) effects become significant for gamma-ray generation,
      although the driving lasers are only at the petawatt level. Our full 3D
      simulations show that directional, ultrabright gamma rays are generated,
      containing [Formula: see text] photons between 5 and 500 MeV within a 10-fs
      duration. The brilliance, up to [Formula: see text] photons [Formula: see text]
      per 0.1% bandwidth at an average photon energy of 20 MeV, is second only to X-ray
      free electron lasers, while the photon energy is 3 orders of magnitude higher
      than the latter. In addition, the gamma ray yield efficiency approaches 10%-that
      is, 5 orders of magnitude higher than the Compton scattering based on laser
      wakefield accelerators. Such high-energy, ultrabright, femtosecond-duration gamma
      rays may find applications in nuclear photonics, radiotherapy, and laboratory
      astrophysics.

PMID- 30224457
TI  - IkappaBzeta is a key transcriptional regulator of IL-36-driven psoriasis-related
      gene expression in keratinocytes.
AB  - Proinflammatory cytokine signaling in keratinocytes plays a crucial role in the
      pathogenesis of psoriasis, a skin disease characterized by hyperproliferation and
      abnormal differentiation of keratinocytes and infiltration of inflammatory cells.
      Although IL-17A and TNFalpha are effective therapeutic targets in psoriasis, IL
      36 has recently emerged as a proinflammatory cytokine. However, little is known
      about IL-36 signaling and its downstream transcriptional responses. Here, we
      found that exposure of keratinocytes to IL-36 induced the expression of
      IkappaBzeta, an atypical IkappaB member and a specific transcriptional regulator
      of selective NF-kappaB target genes. Induction of IkappaBzeta by IL-36 was
      mediated by NF-kappaB and STAT3. In agreement, IL-36-mediated induction of
      IkappaBzeta was found to be required for the expression of various psoriasis
      related genes involved in inflammatory signaling, neutrophil chemotaxis, and
      leukocyte activation. Importantly, IkappaBzeta-knockout mice were protected
      against IL-36-mediated dermatitis, accompanied by reduced proinflammatory gene
      expression, decreased immune cell infiltration, and a lack of keratinocyte
      hyperproliferation. Moreover, expression of IkappaBzeta mRNA was highly up
      regulated in biopsies of psoriasis patients where it coincided with IL36G levels.
      Thus our results uncover an important role for IkappaBzeta in IL-36 signaling and
      validate IkappaBzeta as an attractive target for psoriasis therapy.

PMID- 30224458
TI  - Metal-free class Ie ribonucleotide reductase from pathogens initiates catalysis
      with a tyrosine-derived dihydroxyphenylalanine radical.
AB  - All cells obtain 2'-deoxyribonucleotides for DNA synthesis through the activity
      of a ribonucleotide reductase (RNR). The class I RNRs found in humans and
      pathogenic bacteria differ in (i) use of Fe(II), Mn(II), or both for activation
      of the dinuclear-metallocofactor subunit, beta; (ii) reaction of the reduced
      dimetal center with dioxygen or superoxide for this activation; (iii) requirement
      (or lack thereof) for a flavoprotein activase, NrdI, to provide the superoxide
      from O2; and (iv) use of either a stable tyrosyl radical or a high-valent dimetal
      cluster to initiate each turnover by oxidizing a cysteine residue in the alpha
      subunit to a radical (Cys*). The use of manganese by bacterial class I, subclass
      b-d RNRs, which contrasts with the exclusive use of iron by the eukaryotic Ia
      enzymes, appears to be a countermeasure of certain pathogens against iron
      deprivation imposed by their hosts. Here, we report a metal-free type of class I
      RNR (subclass e) from two human pathogens. The Cys* in its alpha subunit is
      generated by a stable, tyrosine-derived dihydroxyphenylalanine radical (DOPA*) in
      beta. The three-electron oxidation producing DOPA* occurs in Escherichia coli
      only if the beta is coexpressed with the NrdI activase encoded adjacently in the
      pathogen genome. The independence of this new RNR from transition metals, or the
      requirement for a single metal ion only transiently for activation, may afford
      the pathogens an even more potent countermeasure against transition metal
      directed innate immunity.

PMID- 30224459
TI  - A simple developmental model recapitulates complex insect wing venation patterns.
AB  - Insect wings are typically supported by thickened struts called veins. These
      veins form diverse geometric patterns across insects. For many insect species,
      even the left and right wings from the same individual have veins with unique
      topological arrangements, and little is known about how these patterns form. We
      present a large-scale quantitative study of the fingerprint-like "secondary
      veins." We compile a dataset of wings from 232 species and 17 families from the
      order Odonata (dragonflies and damselflies), a group with particularly elaborate
      vein patterns. We characterize the geometric arrangements of veins and develop a
      simple model of secondary vein patterning. We show that our model is capable of
      recapitulating the vein geometries of species from other, distantly related
      winged insect clades.

PMID- 30224460
TI  - cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and
      brain development.
AB  - Normal neural development is essential for the formation of neuronal networks and
      brain function. Cutaneous T cell lymphoma-associated antigen 5
      (cTAGE5)/meningioma expressed antigen 6 (MEA6) plays a critical role in the
      secretion of proteins. However, its roles in the transport of nonsecretory
      cellular components and in brain development remain unknown. Here, we show that
      cTAGE5/MEA6 is important for brain development and function. Conditional knockout
      of cTAGE5/MEA6 in the brain leads to severe defects in neural development,
      including deficits in dendrite outgrowth and branching, spine formation and
      maintenance, astrocyte activation, and abnormal behaviors. We reveal that loss of
      cTAGE5/MEA6 affects the interaction between the coat protein complex II (COPII)
      components, SAR1 and SEC23, leading to persistent activation of SAR1 and defects
      in COPII vesicle formation and transport from the endoplasmic reticulum to the
      Golgi, as well as disturbed trafficking of membrane components in neurons. These
      defects affect not only the transport of materials required for the development
      of dendrites and spines but also the signaling pathways required for neuronal
      development. Because mutations in cTAGE5/MEA6 have been found in patients with
      Fahr's disease, our study potentially also provides insight into the pathogenesis
      of this disorder.

PMID- 30224461
TI  - Effects of self-transcendence on neural responses to persuasive messages and
      health behavior change.
AB  - Self-transcendence refers to a shift in mindset from focusing on self-interests
      to the well-being of others. We offer an integrative neural model of self
      transcendence in the context of persuasive messaging by examining the mechanisms
      of self-transcendence in promoting receptivity to health messages and behavior
      change. Specifically, we posited that focusing on values and activities that
      transcend the self can allow people to see that their self-worth is not tied to a
      specific behavior in question, and in turn become more receptive to subsequent,
      otherwise threatening health information. To test whether inducing self
      transcendent mindsets before message delivery would help overcome defensiveness
      and increase receptivity, we used two priming tasks, affirmation and compassion,
      to elicit a transcendent mindset among 220 sedentary adults. As preregistered,
      those who completed a self-transcendence task before health message exposure,
      compared with controls, showed greater increases in objectively logged levels of
      physical activity throughout the following month. In the brain, self
      transcendence tasks up-regulated activity in a region of the ventromedial
      prefrontal cortex, chosen for its role in positive valuation and reward
      processing. During subsequent health message exposure, self-transcendence priming
      was associated with increased activity in subregions of the ventromedial
      prefrontal cortex, implicated in self-related processing and positive valuation,
      which predicted later decreases in sedentary behavior. The present findings
      suggest that having a positive self-transcendent mindset can increase behavior
      change, in part by increasing neural receptivity to health messaging.

PMID- 30224462
TI  - Leak potassium channels regulate sleep duration.
AB  - A primary goal of sleep research is to understand the molecular basis of sleep.
      Although some sleep/wake-promoting circuits and secreted substances have been
      identified, the detailed molecular mechanisms underlying the regulation of sleep
      duration have been elusive. Here, to address these mechanisms, we developed a
      simple computational model of a cortical neuron with five channels and a pump,
      which recapitulates the cortical electrophysiological characteristics of slow
      wave sleep (SWS) and wakefulness. Comprehensive bifurcation and detailed
      mathematical analyses predicted that leak K+ channels play a role in generating
      the electrophysiological characteristics of SWS, leading to a hypothesis that
      leak K+ channels play a role in the regulation of sleep duration. To test this
      hypothesis experimentally, we comprehensively generated and analyzed 14 KO mice,
      and found that impairment of the leak K+ channel (Kcnk9) decreased sleep
      duration. Based on these results, we hypothesize that leak K+ channels regulate
      sleep duration in mammals.

PMID- 30224463
TI  - Fibroblasts lacking nuclear lamins do not have nuclear blebs or protrusions but
      nevertheless have frequent nuclear membrane ruptures.
AB  - The nuclear lamina, an intermediate filament meshwork lining the inner nuclear
      membrane, is formed by the nuclear lamins (lamins A, C, B1, and B2). Defects or
      deficiencies in individual nuclear lamin proteins have been reported to elicit
      nuclear blebs (protrusions or outpouchings of the nuclear envelope) and increase
      susceptibility for nuclear membrane ruptures. It is unclear, however, how a
      complete absence of nuclear lamins would affect nuclear envelope morphology and
      nuclear membrane integrity (i.e., whether nuclear membrane blebs or protrusions
      would occur and, if not, whether cells would be susceptible to nuclear membrane
      ruptures). To address these issues, we generated mouse embryonic fibroblasts
      (MEFs) lacking all nuclear lamins. The nuclear lamin-deficient MEFs had irregular
      nuclear shapes but no nuclear blebs or protrusions. Despite a virtual absence of
      nuclear blebs, MEFs lacking nuclear lamins had frequent, prolonged, and
      occasionally nonhealing nuclear membrane ruptures. By transmission electron
      microscopy, the inner nuclear membrane in nuclear lamin-deficient MEFs have a
      "wavy" appearance, and there were discrete discontinuities in the inner and outer
      nuclear membranes. Nuclear membrane ruptures were accompanied by a large increase
      in DNA damage, as judged by gamma-H2AX foci. Mechanical stress increased both
      nuclear membrane ruptures and DNA damage, whereas minimizing transmission of
      cytoskeletal forces to the nucleus had the opposite effects.

PMID- 30224464
TI  - Repairable cascaded slide-lock system endows bird feathers with tear-resistance
      and superdurability.
AB  - Bird feathers have aroused tremendous attention for their superdurability against
      tears during long flights through wind and even bushes. Although feathers may
      inevitably be unzipped, the separated feather vanes can be repaired easily by
      bill stroking. However, the mechanism underlying bird feathers' superdurability
      against tears remains unclear. Here, we reveal that the superdurability of bird
      feathers arises from their repairable cascaded slide-lock system, which is
      composed of hooklets, a slide rail, and spines at the end of the slide rail as
      terminating structures. Microscopy with a micronano manipulating system and 3D X
      ray microscopy provided high-level visibility into the 3D fine structures and the
      entire unzipping process of feathers. The hooklets can slide along the slide rail
      reversibly when suffering external forces, and the sliding hooklet can be locked
      by the spine at the ends of barbules when larger pulling forces are applied and
      even slide farther away due to the unzipping of the interlocking structure with
      large deformation of the barbules. The elongation before separation of adjacent
      barbs can reach up to 270%, and the separation force can be maintained above 80%
      of the initial value even after 1,000 cycles of separating and repairing. These
      results prove that the cascaded slide-lock system ensures the superdurability of
      bird feathers against tears.

PMID- 30224465
TI  - Correction for Pereyaslavets et al., On the importance of accounting for nuclear
      quantum effects in ab initio calibrated force fields in biological simulations.

PMID- 30224466
TI  - Jackknife approach to the estimation of mutual information.
AB  - Quantifying the dependence between two random variables is a fundamental issue in
      data analysis, and thus many measures have been proposed. Recent studies have
      focused on the renowned mutual information (MI) [Reshef DN, et al. (2011) Science
      334:1518-1524]. However, "Unfortunately, reliably estimating mutual information
      from finite continuous data remains a significant and unresolved problem" [Kinney
      JB, Atwal GS (2014) Proc Natl Acad Sci USA 111:3354-3359]. In this paper, we
      examine the kernel estimation of MI and show that the bandwidths involved should
      be equalized. We consider a jackknife version of the kernel estimate with
      equalized bandwidth and allow the bandwidth to vary over an interval. We estimate
      the MI by the largest value among these kernel estimates and establish the
      associated theoretical underpinnings.

PMID- 30224467
TI  - Dedifferentiation of caudate functional connectivity and striatal dopamine
      transporter density predict memory change in normal aging.
AB  - Age-related changes in striatal function are potentially important for predicting
      declining memory performance over the adult life span. Here, we used fMRI to
      measure functional connectivity of caudate subfields with large-scale association
      networks and positron emission tomography to measure striatal dopamine
      transporter (DAT) density in 51 older adults (age 65-86 years) who received
      annual cognitive testing for up to 7 years (mean = 5.59, range 2-7 years).
      Analyses showed that cortical-caudate functional connectivity was less
      differentiated in older compared with younger adults (n = 63, age 18-32 years).
      Unlike in younger adults, the central lateral caudate was less strongly coupled
      with the frontal parietal control network in older adults. Older adults also
      showed less "decoupling" of the caudate from other networks, including areas of
      the default network (DN) and the hippocampal complex. Contrary to expectations,
      less decoupling between caudate and the DN was not associated with an age-related
      reduction of striatal DAT, suggesting that neurobiological changes in the cortex
      may drive dedifferentiation of cortical-caudate connectivity. Reduction of
      specificity in functional coupling between caudate and regions of the DN
      predicted memory decline over subsequent years at older ages. The age-related
      reduction in striatal DAT density also predicted memory decline, suggesting that
      a relation between striatal functions and memory decline in aging is
      multifaceted. Collectively, the study provides evidence highlighting the
      association of age-related differences in striatal function to memory decline in
      normal aging.

PMID- 30224469
TI  - Correction for Lanaspa et al., High salt intake causes leptin resistance and
      obesity in mice by stimulating endogenous fructose production and metabolism.

PMID- 30224468
TI  - Assimilation of formic acid and CO2 by engineered Escherichia coli equipped with
      reconstructed one-carbon assimilation pathways.
AB  - Gaseous one-carbon (C1) compounds or formic acid (FA) converted from CO2 can be
      an attractive raw material for bio-based chemicals. Here, we report the
      development of Escherichia coli strains assimilating FA and CO2 through the
      reconstructed tetrahydrofolate (THF) cycle and reverse glycine cleavage (gcv)
      pathway. The Methylobacterium extorquens formate-THF ligase, methenyl-THF
      cyclohydrolase, and methylene-THF dehydrogenase genes were expressed to allow FA
      assimilation. The gcv reaction was reversed by knocking out the repressor gene
      (gcvR) and overexpressing the gcvTHP genes. This engineered strain synthesized
      96% and 86% of proteinogenic glycine and serine, respectively, from FA and CO2 in
      a glucose-containing medium. Native serine deaminase converted serine to
      pyruvate, showing 4.5% of pyruvate-forming flux comes from FA and CO2 The
      pyruvate-forming flux from FA and CO2 could be increased to 14.9% by knocking out
      gcvR, pflB, and serA, chromosomally expressing gcvTHP under trc, and
      overexpressing the reconstructed THF cycle, gcvTHP, and lpd genes in one vector.
      To reduce glucose usage required for energy and redox generation, the Candida
      boidinii formate dehydrogenase (Fdh) gene was expressed. The resulting strain
      showed specific glucose, FA, and CO2 consumption rates of 370.2, 145.6, and 14.9
      mg?g dry cell weight (DCW)-1?h-1, respectively. The C1 assimilation pathway
      consumed 21.3 wt% of FA. Furthermore, cells sustained slight growth using only FA
      and CO2 after glucose depletion, suggesting that combined use of the C1
      assimilation pathway and C. boidinii Fdh will be useful for eventually developing
      a strain capable of utilizing FA and CO2 without an additional carbon source such
      as glucose.

PMID- 30224470
TI  - Regulatory gamma1 subunits defy symmetry in functional modulation of BK channels.
AB  - Structural symmetry is a hallmark of homomeric ion channels. Nonobligatory
      regulatory proteins can also critically define the precise functional role of
      such channels. For instance, the pore-forming subunit of the large conductance
      voltage and calcium-activated potassium (BK, Slo1, or KCa1.1) channels encoded by
      a single KCa1.1 gene assembles in a fourfold symmetric fashion. Functional
      diversity arises from two families of regulatory subunits, beta and gamma, which
      help define the range of voltages over which BK channels in a given cell are
      activated, thereby defining physiological roles. A BK channel can contain zero to
      four beta subunits per channel, with each beta subunit incrementally influencing
      channel gating behavior, consistent with symmetry expectations. In contrast, a
      gamma1 subunit (or single type of gamma1 subunit complex) produces a functionally
      all-or-none effect, but the underlying stoichiometry of gamma1 assembly and
      function remains unknown. Here we utilize two distinct and independent methods, a
      Forster resonance energy transfer-based optical approach and a functional
      reporter in single-channel recordings, to reveal that a BK channel can contain up
      to four gamma1 subunits, but a single gamma1 subunit suffices to induce the full
      gating shift. This requires that the asymmetric association of a single
      regulatory protein can act in a highly concerted fashion to allosterically
      influence conformational equilibria in an otherwise symmetric K+ channel.

PMID- 30224471
TI  - Structural mechanism of Myb-MuvB assembly.
AB  - The MuvB transcriptional regulatory complex, which controls cell-cycle-dependent
      gene expression, cooperates with B-Myb to activate genes required for the G2 and
      M phases of the cell cycle. We have identified the domain in B-Myb that is
      essential for the assembly of the Myb-MuvB (MMB) complex. We determined a crystal
      structure that reveals how this B-Myb domain binds MuvB through the adaptor
      protein LIN52 and the scaffold protein LIN9. The structure and biochemical
      analysis provide an understanding of how oncogenic B-Myb is recruited to regulate
      genes required for cell-cycle progression, and the MMB interface presents a
      potential therapeutic target to inhibit cancer cell proliferation.

PMID- 30224473
TI  - Correction for Schickinger et al., Tethered multifluorophore motion reveals
      equilibrium transition kinetics of single DNA double helices.

PMID- 30224472
TI  - Functional profiling of circulating tumor cells with an integrated vortex capture
      and single-cell protease activity assay.
AB  - Tumor cells are hypothesized to use proteolytic enzymes to facilitate invasion.
      Whether circulating tumor cells (CTCs) secrete these enzymes to aid metastasis is
      unknown. A quantitative and high-throughput approach to assay CTC secretion is
      needed to address this question. We developed an integrated microfluidic system
      that concentrates rare cancer cells >100,000-fold from 1 mL of whole blood into
      ~50,000 2-nL drops composed of assay reagents within 15 min. The system isolates
      CTCs by size, exchanges fluid around CTCs to remove contaminants, introduces a
      matrix metalloprotease (MMP) substrate, and encapsulates CTCs into microdroplets.
      We found CTCs from prostate cancer patients possessed above baseline levels of
      MMP activity (1.7- to 200-fold). Activity of CTCs was generally higher than
      leukocytes from the same patient (average CTC/leukocyte MMP activity ratio, 2.6
      +/- 1.5). Higher MMP activity of CTCs suggests active proteolytic processes that
      may facilitate invasion or immune evasion and be relevant phenotypic biomarkers
      enabling companion diagnostics for anti-MMP therapies.

PMID- 30224474
TI  - Human influences on the strength of phenotypic selection.
AB  - Human activities are driving rapid phenotypic change in many species, with
      harvesting considered to be a particularly potent evolutionary force. We
      hypothesized that faster evolutionary change in human-disturbed populations could
      be caused by a strengthening of phenotypic selection, for example, if human
      disturbances trigger maladaptation and/or increase the opportunity for selection.
      We tested this hypothesis by synthesizing 1,366 phenotypic selection coefficients
      from 37 species exposed to various anthropogenic disturbances, including harvest.
      We used a paired design that only included studies measuring selection on the
      same traits in both human-disturbed and control (not obviously human-disturbed
      "natural") populations. Surprisingly, this meta-analysis did not reveal stronger
      selection in human-disturbed environments; in fact, we even found some evidence
      that human disturbances might slightly reduce selection strength. The only clear
      exceptions were two fisheries showing very strong harvest selection. On closer
      inspection, we discovered that many disturbances weakened selection by increasing
      absolute fitness and by decreasing the opportunity for selection-thus explaining
      what initially seemed a counterintuitive result. We discuss how human
      disturbances can sometimes weaken rather than strengthen selection, and why
      measuring the total effect of disturbances on selection is exceedingly difficult.
      Despite these challenges, documenting human influences on selection can reveal
      disturbances with particularly strong effects (e.g., fishing), and thus better
      inform the management of populations exposed to these disturbances.

PMID- 30224476
TI  - Correction for Sharp et al., Psychological targeting.

PMID- 30224475
TI  - Converging evidence for functional and structural segregation within the left
      ventral occipitotemporal cortex in reading.
AB  - The ventral occipitotemporal cortex (vOTC) is crucial for recognizing visual
      patterns, and previous evidence suggests that there may be different subregions
      within the vOTC involved in the rapid identification of word forms. Here, we
      characterize vOTC reading circuitry using a multimodal approach combining
      functional, structural, and quantitative MRI and behavioral data. Two main word
      responsive vOTC areas emerged: a posterior area involved in visual feature
      extraction, structurally connected to the intraparietal sulcus via the vertical
      occipital fasciculus; and an anterior area involved in integrating information
      with other regions of the language network, structurally connected to the angular
      gyrus via the posterior arcuate fasciculus. Furthermore, functional activation in
      these vOTC regions predicted reading behavior outside of the scanner. Differences
      in the microarchitectonic properties of gray-matter cells in these segregated
      areas were also observed, in line with earlier cytoarchitectonic evidence. These
      findings advance our understanding of the vOTC circuitry by linking functional
      responses to anatomical structure, revealing the pathways of distinct reading
      related processes.

PMID- 30224477
TI  - Control of CCND1 ubiquitylation by the catalytic SAGA subunit USP22 is essential
      for cell cycle progression through G1 in cancer cells.
AB  - Overexpression of the deubiquitylase ubiquitin-specific peptidase 22 (USP22) is a
      marker of aggressive cancer phenotypes like metastasis, therapy resistance, and
      poor survival. Functionally, this overexpression of USP22 actively contributes to
      tumorigenesis, as USP22 depletion blocks cancer cell cycle progression in vitro,
      and inhibits tumor progression in animal models of lung, breast, bladder,
      ovarian, and liver cancer, among others. Current models suggest that USP22
      mediates these biological effects via its role in epigenetic regulation as a
      subunit of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional cofactor
      complex. Challenging the dogma, we report here a nontranscriptional role for
      USP22 via a direct effect on the core cell cycle machinery: that is, the
      deubiquitylation of the G1 cyclin D1 (CCND1). Deubiquitylation by USP22 protects
      CCND1 from proteasome-mediated degradation and occurs separately from the
      canonical phosphorylation/ubiquitylation mechanism previously shown to regulate
      CCND1 stability. We demonstrate that control of CCND1 is a key mechanism by which
      USP22 mediates its known role in cell cycle progression. Finally, USP22 and CCND1
      levels correlate in patient lung and colorectal cancer samples and our
      preclinical studies indicate that targeting USP22 in combination with CDK
      inhibitors may offer an approach for treating cancer patients whose tumors
      exhibit elevated CCND1.

PMID- 30224478
TI  - Snapshots of a modified nucleotide moving through the confines of a DNA
      polymerase.
AB  - DNA polymerases have evolved to process the four canonical nucleotides
      accurately. Nevertheless, these enzymes are also known to process modified
      nucleotides, which is the key to numerous core biotechnology applications.
      Processing of modified nucleotides includes incorporation of the modified
      nucleotide and postincorporation elongation to proceed with the synthesis of the
      nascent DNA strand. The structural basis for postincorporation elongation is
      currently unknown. We addressed this issue and successfully crystallized KlenTaq
      DNA polymerase in six closed ternary complexes containing the enzyme, the
      modified DNA substrate, and the incoming nucleotide. Each structure shows a high
      resolution snapshot of the elongation of a modified primer, where the
      modification "moves" from the 3'-primer terminus upstream to the sixth nucleotide
      in the primer strand. Combining these data with quantum mechanics/molecular
      mechanics calculations and biochemical studies elucidates how the enzyme and the
      modified substrate mutually modulate their conformations without compromising the
      enzyme's activity significantly. The study highlights the plasticity of the
      system as origin of the broad substrate properties of DNA polymerases and
      facilitates the design of improved systems.

PMID- 30224479
TI  - Targeted profiling of RNA translation reveals mTOR-4EBP1/2-independent
      translation regulation of mRNAs encoding ribosomal proteins.
AB  - The PI3K-Akt-mTOR signaling pathway is a master regulator of RNA translation.
      Pharmacological inhibition of this pathway preferentially and coordinately
      suppresses, in a 4EBP1/2-dependent manner, translation of mRNAs encoding
      ribosomal proteins. However, it is unclear whether mechanistic target of
      rapamycin (mTOR)-4EBP1/2 is the exclusive translation regulator of this group of
      genes, and furthermore, systematic searches for novel translation modulators have
      been immensely challenging because of difficulties in scaling existing RNA
      translation profiling assays. Here, we developed a rapid and highly scalable
      approach for gene-specific quantitation of RNA translation, termed Targeted
      Profiling of RNA Translation (TPRT). We applied this technique in a chemical
      screen for translation modulators, and identified numerous preclinical and
      clinical therapeutic compounds, with diverse nominal targets, that preferentially
      suppress translation of ribosomal proteins. Surprisingly, some of these compounds
      act in a manner that bypasses canonical regulation by mTOR-4EBP1/2. Instead,
      these compounds exert their translation effects in a manner that is dependent on
      GCN2-eIF2alpha, a central signaling axis within the integrated stress response.
      Furthermore, we were also able to identify metabolic perturbations that also
      suppress ribosomal protein translation in an mTOR-independent manner. Together,
      we describe a translation assay that is directly applicable to large-scale RNA
      translation studies, and that enabled us to identify a noncanonical, mTOR
      independent mode for translation regulation of ribosomal proteins.

PMID- 30224480
TI  - Self-organization into ferroelectric and antiferroelectric crystals via the
      interplay between particle shape and dipolar interaction.
AB  - Ferroelectricity and antiferroelectricity are widely seen in various types of
      condensed matter and are of technological significance not only due to their
      electrical switchability but also due to intriguing cross-coupling effects such
      as electro-mechanical and electro-caloric effects. The control of the two types
      of dipolar order has practically been made by changing the ionic radius of a
      constituent atom or externally applying strain for inorganic crystals and by
      changing the shape of a molecule for organic crystals. However, the basic
      physical principle behind such controllability involving crystal-lattice
      organization is still unknown. On the basis of a physical picture that a
      competition of dipolar order with another type of order is essential to
      understand this phenomenon, here we develop a simple model system composed of
      spheroid-like particles with a permanent dipole, which may capture an essence of
      this important structural transition in organic systems. In this model, we reveal
      that energetic frustration between the two types of anisotropic interactions,
      dipolar and steric interactions, is a key to control not only the phase
      transition but also the coupling between polarization and strain. Our finding
      provides a fundamental physical principle for self-organization to a crystal with
      desired dipolar order and realization of large electro-mechanical effects.

PMID- 30224481
TI  - Phospho-dependent recruitment of the yeast NuA4 acetyltransferase complex by MRX
      at DNA breaks regulates RPA dynamics during resection.
AB  - The KAT5 (Tip60/Esa1) histone acetyltransferase is part of NuA4, a large
      multifunctional complex highly conserved from yeast to mammals that targets
      lysines on H4 and H2A (X/Z) tails for acetylation. It is essential for cell
      viability, being a key regulator of gene expression, cell proliferation, and stem
      cell renewal and an important factor for genome stability. The NuA4 complex is
      directly recruited near DNA double-strand breaks (DSBs) to facilitate repair, in
      part through local chromatin modification and interplay with 53BP1 during the DNA
      damage response. While NuA4 is detected early after appearance of the lesion, its
      precise mechanism of recruitment remains to be defined. Here, we report a
      stepwise recruitment of yeast NuA4 to DSBs first by a DNA damage-induced
      phosphorylation-dependent interaction with the Xrs2 subunit of the Mre11-Rad50
      Xrs2 (MRX) complex bound to DNA ends. This is followed by a DNA resection
      dependent spreading of NuA4 on each side of the break along with the ssDNA
      binding replication protein A (RPA). Finally, we show that NuA4 can acetylate RPA
      and regulate the dynamics of its binding to DNA, hence targeting locally both
      histone and nonhistone proteins for lysine acetylation to coordinate repair.

PMID- 30224482
TI  - On the origin of the elusive first intermediate of CO2 electroreduction.
AB  - We resolve the long-standing controversy about the first step of the CO2
      electroreduction to fuels in aqueous electrolytes by providing direct
      spectroscopic evidence that the first intermediate of the CO2 conversion to
      formate on copper is a carboxylate anion *CO2 - coordinated to the surface
      through one of its C-O bonds. We identify this intermediate and gain insight into
      its formation, its chemical and electronic properties, as well as its dependence
      on the electrode potential by taking advantage of a cutting-edge methodology that
      includes operando surface-enhanced Raman scattering (SERS) empowered by isotope
      exchange and electrochemical Stark effects, reaction kinetics (Tafel) analysis,
      and density functional theory (DFT) simulations. The SERS spectra are measured on
      an operating Cu surface. These results advance the mechanistic understanding of
      CO2 electroreduction and its selectivity to carbon monoxide and formate.

PMID- 30224483
TI  - Crimping-induced structural gradients explain the lasting strength of poly l
      lactide bioresorbable vascular scaffolds during hydrolysis.
AB  - Biodegradable polymers open the way to treatment of heart disease using transient
      implants (bioresorbable vascular scaffolds, BVSs) that overcome the most serious
      complication associated with permanent metal stents-late stent thrombosis. Here,
      we address the long-standing paradox that the clinically approved BVS maintains
      its radial strength even after 9 mo of hydrolysis, which induces a ~40% decrease
      in the poly l-lactide molecular weight (Mn). X-ray microdiffraction evidence of
      nonuniform hydrolysis in the scaffold reveals that regions subjected to tensile
      stress during crimping develop a microstructure that provides strength and
      resists hydrolysis. These beneficial morphological changes occur where they are
      needed most-where stress is localized when a radial load is placed on the
      scaffold. We hypothesize that the observed decrease in Mn reflects the majority
      of the material, which is undeformed during crimping. Thus, the global measures
      of degradation may be decoupled from the localized, degradation-resistant regions
      that confer the ability to support the artery for the first several months after
      implantation.

PMID- 30224484
TI  - Erroneous ribosomal RNAs promote the generation of antisense ribosomal siRNA.
AB  - Ribosome biogenesis is a multistep process, during which mistakes can occur at
      any step of pre-rRNA processing, modification, and ribosome assembly.
      Misprocessed rRNAs are usually detected and degraded by surveillance machineries.
      Recently, we identified a class of antisense ribosomal siRNAs (risiRNAs) that
      down-regulate pre-rRNAs through the nuclear RNAi pathway. To further understand
      the biological roles of risiRNAs, we conducted both forward and reverse genetic
      screens to search for more suppressor of siRNA (susi) mutants. We isolated a
      number of genes that are broadly conserved from yeast to humans and are involved
      in pre-rRNA modification and processing. Among them, SUSI-2(ceRRP8) is homologous
      to human RRP8 and engages in m1A methylation of the 26S rRNA. C27F2.4(ceBUD23) is
      an m7G-methyltransferase of the 18S rRNA. E02H1.1(ceDIMT1L) is a predicted
      m6(2)Am6(2)A-methyltransferase of the 18S rRNA. Mutation of these genes led to a
      deficiency in modification of rRNAs and elicited accumulation of risiRNAs, which
      further triggered the cytoplasmic-to-nuclear and cytoplasmic-to-nucleolar
      translocations of the Argonaute protein NRDE-3. The rRNA processing deficiency
      also resulted in accumulation of risiRNAs. We also isolated SUSI-3(RIOK-1), which
      is similar to human RIOK1, that cleaves the 20S rRNA to 18S. We further utilized
      RNAi and CRISPR-Cas9 technologies to perform candidate-based reverse genetic
      screens and identified additional pre-rRNA processing factors that suppressed
      risiRNA production. Therefore, we concluded that erroneous rRNAs can trigger
      risiRNA generation and subsequently, turn on the nuclear RNAi-mediated gene
      silencing pathway to inhibit pre-rRNA expression, which may provide a quality
      control mechanism to maintain homeostasis of rRNAs.

PMID- 30224485
TI  - Transcriptional elongation factor Paf1 core complex adopts a spirally wrapped
      solenoidal topology.
AB  - The polymerase-associated factor 1 (Paf1) complex is a general transcription
      elongation factor of RNA polymerase II, which is composed of five core subunits,
      Paf1, Ctr9, Cdc73, Leo1, and Rtf1, and functions as a diverse platform that
      broadly affects gene expression genome-wide. In this study, we solved the 2.9-A
      crystal structure of the core region composed of the Ctr9-Paf1-Cdc73 ternary
      complex from a thermophilic fungi, which provides a structural perspective of the
      molecular details of the organization and interactions involving the Paf1
      subunits in the core complex. We find that Ctr9 is composed of 21
      tetratricopeptide repeat (TPR) motifs that wrap three circular turns in a right
      handed superhelical manner around the N-terminal region of an elongated single
      polypeptide-chain scaffold of Paf1. The Cdc73 fragment is positioned within the
      surface groove of Ctr9, where it contacts mainly with Ctr9 and minimally with
      Paf1. We also identified that the Paf1 complex preferentially binds single-strand
      containing DNAs. Our work provides structural insights into the overall
      architecture of the Paf1 complex and paves the road forward for understanding the
      molecular mechanisms of the Paf1 complex in transcriptional regulation.

PMID- 30224486
TI  - Reviving oncogenic addiction to MET bypassed by BRAF (G469A) mutation.
AB  - Cancer clonal evolution is based on accrual of driving genetic alterations that
      are expected to cooperate and progressively increase malignancy. Little is known
      on whether any genetic alteration can hinder the oncogenic function of a
      coexisting alteration, so that therapeutic targeting of the one can,
      paradoxically, revive the function of the other. We report the case of a driver
      oncogene (MET) that is not only bypassed, but also disabled by the mutation of a
      downstream transducer (BRAF), and reignited by inhibition of the latter. In a
      metastasis originated from a cancer of unknown primary (CUP), the MET oncogene
      was amplified eightfold, but unexpectedly, the kinase was dephosphorylated and
      inactive. As result, specific drugs targeting MET (JNJ-38877605) failed to
      inhibit growth of xenografts derived from the patient. In addition to MET
      amplification, the patient harbored, as sole proliferative driver, a mutation
      hyperactivating BRAF (G469A). Surprisingly, specific blockade of the BRAF pathway
      was equally ineffective, and it was accompanied by rephosphorylation of the
      amplified MET oncoprotein and by revived addiction to MET. Mechanistically, MET
      inactivation in the context of the BRAF-activating mutation is driven through a
      negative feedback loop involving inactivation of PP2A phosphatase, which in turn
      leads to phosphorylation on MET inhibitory Ser985. Disruption of this feedback
      loop allows PP2A reactivation, removing the inhibitory phosphorylation from
      Ser985 and thereby unleashing MET kinase activity. Evidence is provided for a
      mechanism of therapeutic resistance to single-oncoprotein targeting, based on
      reactivation of a genetic alteration functionally dormant in targeted cancer
      cells.

PMID- 30224487
TI  - Synchronization of energy consumption by human societies throughout the Holocene.
AB  - We conduct a global comparison of the consumption of energy by human populations
      throughout the Holocene and statistically quantify coincident changes in the
      consumption of energy over space and time-an ecological phenomenon known as
      synchrony. When populations synchronize, adverse changes in ecosystems and social
      systems may cascade from society to society. Thus, to develop policies that favor
      the sustained use of resources, we must understand the processes that cause the
      synchrony of human populations. To date, it is not clear whether human societies
      display long-term synchrony or, if they do, the potential causes. Our analysis
      begins to fill this knowledge gap by quantifying the long-term synchrony of human
      societies, and we hypothesize that the synchrony of human populations results
      from (i) the creation of social ties that couple populations over smaller scales
      and (ii) much larger scale, globally convergent trajectories of cultural
      evolution toward more energy-consuming political economies with higher carrying
      capacities. Our results suggest that the process of globalization is a natural
      consequence of evolutionary trajectories that increase the carrying capacities of
      human societies.

PMID- 30224488
TI  - Evolutionary journey of the retroviral restriction gene Fv1.
AB  - Both exogenous and endogenous retroviruses have long been studied in mice, and
      some of the earliest mouse studies focused on the heritability of genetic factors
      influencing permissivity and resistance to infection. The prototypic retroviral
      restriction factor, Fv1, is now understood to exhibit a degree of control across
      multiple retroviral genera and is highly diverse within Mus To better understand
      the age and evolutionary history of Fv1, a comprehensive survey of the Muroidea
      was conducted, allowing the progenitor integration to be dated to ~45 million
      years. Intact coding potential is visible beyond Mus, and sequence analysis
      reveals strong signatures of positive selection also within field mice, Apodemus
      Fv1's survival for such a period implies a recurring and shifting retroviral
      burden imparting the necessary selective pressures-an influence likely also
      common to analogous factors. Regions of Fv1 adapt cooperatively, highlighting its
      preference for repeated structures and suggesting that this functionally
      constrained aspect of the retroviral capsid lattice presents a common target in
      the evolution of intrinsic immunity.

PMID- 30224490
TI  - Correction for Loyer et al., Drosophila E-cadherin is required for the
      maintenance of ring canals anchoring to mechanically withstand tissue growth.

PMID- 30224489
TI  - Molecular mechanisms of the interhead coordination by interhead tension in
      cytoplasmic dyneins.
AB  - Cytoplasmic dyneins play a major role in retrograde cellular transport by moving
      vesicles and organelles along microtubule filaments. Dyneins are multidomain
      motor proteins with two heads that coordinate their motion via their interhead
      tension. Compared with the leading head, the trailing head has a higher
      detachment rate from microtubules, facilitating the movement. However, the
      molecular mechanism of such coordination is unknown. To elucidate this mechanism,
      we performed molecular dynamics simulations on a cytoplasmic dynein with a
      structure-based coarse-grained model that probes the effect of the interhead
      tension on the structure. The tension creates a torque that influences the head
      rotating about its stalk. The conformation of the stalk switches from the alpha
      registry to the beta registry during the rotation, weakening the binding affinity
      to microtubules. The directions of the tension and the torque of the leading head
      are opposite to those of the trailing head, breaking the structural symmetry
      between the heads. The leading head transitions less often to the beta registry
      than the trailing head. The former thus has a greater binding affinity to the
      microtubule than the latter. We measured the moment arm of the torque from a
      dynein structure in the simulations to develop a phenomenological model that
      captures the influence of the head rotating about its stalk on the differential
      detachment rates of the two heads. Our study provides a consistent molecular
      picture for interhead coordination via interhead tension.

PMID- 30224491
TI  - Why grit requires perseverance and passion to positively predict performance.
AB  - Prior studies linking grit-defined as perseverance and passion for long-term
      goals-to performance are beset by contradictory evidence. As a result,
      commentators have increasingly declared that grit has limited effects. We propose
      that this inconsistent evidence has occurred because prior research has
      emphasized perseverance and ignored, both theoretically and empirically, the
      critical role of passion, which we define as a strong feeling toward a personally
      important value/preference that motivates intentions and behaviors to express
      that value/preference. We suggest that combining the grit scale-which only
      captures perseverance-with a measure that assesses whether individuals attain
      desired levels of passion will predict performance. We first metaanalyzed 127
      studies (n = 45,485) that used the grit scale and assessed performance, and found
      that effect sizes are larger in studies where participants were more passionate
      for the performance domain. Second, in a survey of employees matched to
      supervisor-rated job performance (n = 422), we found that the combination of
      perseverance, measured through the grit scale, and passion attainment, measured
      through a new scale, predicted higher performance. A final study measured
      perseverance and passion attainment in a sample of students (n = 248) and linked
      these to their grade-point average (GPA), finding that the combination of
      perseverance and passion attainment predicted higher GPAs in part through
      increased immersion. The present results help resolve the mixed evidence of
      grit's relationship with performance by highlighting the important role that
      passion plays in predicting performance. By adequately measuring both
      perseverance and passion, the present research uncovers grit's true predictive
      power.

PMID- 30224492
TI  - Uneven balance of power between hypothalamic peptidergic neurons in the control
      of feeding.
AB  - Two classes of peptide-producing neurons in the arcuate nucleus (Arc) of the
      hypothalamus are known to exert opposing actions on feeding: the anorexigenic
      neurons that express proopiomelanocortin (POMC) and the orexigenic neurons that
      express agouti-related protein (AgRP) and neuropeptide Y (NPY). These neurons are
      thought to arise from a common embryonic progenitor, but our anatomical and
      functional understanding of the interplay of these two peptidergic systems that
      contribute to the control of feeding remains incomplete. The present study uses a
      combination of optogenetic stimulation with viral and transgenic approaches,
      coupled with neural activity mapping and brain transparency visualization to
      demonstrate the following: (i) selective activation of Arc POMC neurons inhibits
      food consumption rapidly in unsated animals; (ii) activation of Arc neurons
      arising from POMC-expressing progenitors, including POMC and a subset of AgRP
      neurons, triggers robust feeding behavior, even in the face of satiety signals
      from POMC neurons; (iii) the opposing effects on food intake are associated with
      distinct neuronal projection and activation patterns of adult hypothalamic POMC
      neurons versus Arc neurons derived from POMC-expressing lineages; and (iv) the
      increased food intake following the activation of orexigenic neurons derived from
      POMC-expressing progenitors engages an extensive neural network that involves the
      endogenous opioid system. Together, these findings shed further light on the
      dynamic balance between two peptidergic systems in the moment-to-moment
      regulation of feeding behavior.

PMID- 30224493
TI  - Metabolic regulation and glucose sensitivity of cortical radial glial cells.
AB  - The primary stem cells of the cerebral cortex are the radial glial cells (RGCs),
      and disturbances in their operation lead to myriad brain disorders in all mammals
      from mice to humans. Here, we found in mice that maternal gestational obesity and
      hyperglycemia can impair the maturation of RGC fibers and delay cortical
      neurogenesis. To investigate potential mechanisms, we used optogenetic live
      imaging approaches in embryonic cortical slices. We found that Ca2+ signaling
      regulates mitochondrial transport and is crucial for metabolic support in RGC
      fibers. Cyclic intracellular Ca2+ discharge from localized RGC fiber segments
      detains passing mitochondria and ensures their proper distribution and enrichment
      at specific sites such as endfeet. Impairment of mitochondrial function caused an
      acute loss of Ca2+ signaling, while hyperglycemia decreased Ca2+ activity and
      impaired mitochondrial transport, leading to degradation of the RGC scaffold. Our
      findings uncover a physiological mechanism indicating pathways by which
      gestational metabolic disturbances can interfere with brain development.

PMID- 30224494
TI  - Influenza hemagglutinin membrane anchor.
AB  - Viruses with membranes fuse them with cellular membranes, to transfer their
      genomes into cells at the beginning of infection. For Influenza virus, the
      membrane glycoprotein involved in fusion is the hemagglutinin (HA), the 3D
      structure of which is known from X-ray crystallographic studies. The soluble
      ectodomain fragments used in these studies lacked the "membrane anchor" portion
      of the molecule. Since this region has a role in membrane fusion, we have
      determined its structure by analyzing the intact, full-length molecule in a
      detergent micelle, using cryo-EM. We have also compared the structures of full
      length HA-detergent micelles with full-length HA-Fab complex detergent micelles,
      to describe an infectivity-neutralizing monoclonal Fab that binds near the
      ectodomain membrane anchor junction. We determine a high-resolution HA structure
      which compares favorably in detail with the structure of the ectodomain seen by X
      ray crystallography; we detect, clearly, all five carbohydrate side chains of HA;
      and we find that the ectodomain is joined to the membrane anchor by flexible,
      eight-residue-long, linkers. The linkers extend into the detergent micelle to
      join a central triple-helical structure that is a major component of the membrane
      anchor.

PMID- 30224495
TI  - Modified mevalonate pathway of the archaeon Aeropyrum pernix proceeds via trans
      anhydromevalonate 5-phosphate.
AB  - The modified mevalonate pathway is believed to be the upstream biosynthetic route
      for isoprenoids in general archaea. The partially identified pathway has been
      proposed to explain a mystery surrounding the lack of phosphomevalonate kinase
      and diphosphomevalonate decarboxylase by the discovery of a conserved enzyme,
      isopentenyl phosphate kinase. Phosphomevalonate decarboxylase was considered to
      be the missing link that would fill the vacancy in the pathway between mevalonate
      5-phosphate and isopentenyl phosphate. This enzyme was recently discovered from
      haloarchaea and certain Chroloflexi bacteria, but their enzymes are close
      homologs of diphosphomevalonate decarboxylase, which are absent in most archaea.
      In this study, we used comparative genomic analysis to find two enzymes from a
      hyperthermophilic archaeon, Aeropyrum pernix, that can replace phosphomevalonate
      decarboxylase. One enzyme, which has been annotated as putative aconitase,
      catalyzes the dehydration of mevalonate 5-phosphate to form a previously unknown
      intermediate, trans-anhydromevalonate 5-phosphate. Then, another enzyme belonging
      to the UbiD-decarboxylase family, which likely requires a UbiX-like partner,
      converts the intermediate into isopentenyl phosphate. Their activities were
      confirmed by in vitro assay with recombinant enzymes and were also detected in
      cell-free extract from A. pernix These data distinguish the modified mevalonate
      pathway of A. pernix and likely, of the majority of archaea from all known
      mevalonate pathways, such as the eukaryote-type classical pathway, the
      haloarchaea-type modified pathway, and another modified pathway recently
      discovered from Thermoplasma acidophilum.

PMID- 30224496
TI  - The PqsE and RhlR proteins are an autoinducer synthase-receptor pair that control
      virulence and biofilm development in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a leading cause of life-threatening nosocomial
      infections. Many virulence factors produced by P. aeruginosa are controlled by
      the cell-to-cell communication process called quorum sensing (QS). QS depends on
      the synthesis, release, and groupwide response to extracellular signaling
      molecules called autoinducers. P. aeruginosa possesses two canonical LuxI/R-type
      QS systems, LasI/R and RhlI/R, that produce and detect 3OC12-homoserine lactone
      and C4-homoserine lactone, respectively. Previously, we discovered that RhlR
      regulates both RhlI-dependent and RhlI-independent regulons, and we proposed that
      an alternative ligand functions together with RhlR to control the target genes in
      the absence of RhlI. Here, we report the identification of an enzyme, PqsE, which
      is the alternative-ligand synthase. Using biofilm analyses, reporter assays, site
      directed mutagenesis, protein biochemistry, and animal infection studies, we show
      that the PqsE-produced alternative ligand is the key autoinducer that promotes
      virulence gene expression. Thus, PqsE can be targeted for therapeutic
      intervention. Furthermore, this work shows that PqsE and RhlR function as a QS
      autoinducer synthase-receptor pair that drives group behaviors in P. aeruginosa.

PMID- 30224497
TI  - Endogenous rewards promote cooperation.
AB  - Sustaining cooperation in social dilemmas is a fundamental objective in the
      social and biological sciences. Although providing a punishment option to
      community members in the public goods game (PGG) has been shown to effectively
      promote cooperation, this has some serious disadvantages; these include
      destruction of a society's physical resources as well as its overall social
      capital. A more efficient approach may be to instead employ a reward mechanism.
      We propose an endogenous reward mechanism that taxes the gross income of each
      round's PGG play and assigns the amount to a fund; each player then decides how
      to distribute his or her share of the fund as rewards to other members of the
      community. Our mechanism successfully reverses the decay trend and achieves a
      high level of contribution with budget-balanced rewards that require no external
      funding, an important condition for practical implementation. Simulations based
      on type-specific estimations indicate that the payoff-based conditional
      cooperation model explains the observed treatment effects well.

PMID- 30224499
TI  - What's happening in Neurology(r)Genetics.

PMID- 30224500
TI  - Of the brain, by the brain, and for the brain.

PMID- 30224498
TI  - Potentiating KCC2 activity is sufficient to limit the onset and severity of
      seizures.
AB  - The type 2 K+/Cl- cotransporter (KCC2) allows neurons to maintain low
      intracellular levels of Cl-, a prerequisite for efficient synaptic inhibition.
      Reductions in KCC2 activity are evident in epilepsy; however, whether these
      deficits directly contribute to the underlying pathophysiology remains
      controversial. To address this issue, we created knock-in mice in which
      threonines 906 and 1007 within KCC2 have been mutated to alanines (KCC2
      T906A/T1007A), which prevents its phospho-dependent inactivation. The respective
      mice appeared normal and did not show any overt phenotypes, and basal neuronal
      excitability was unaffected. KCC2-T906A/T1007A mice exhibited increased basal
      neuronal Cl- extrusion, without altering total or plasma membrane accumulation of
      KCC2. Critically, activity-induced deficits in synaptic inhibition were reduced
      in the mutant mice. Consistent with this, enhanced KCC2 was sufficient to limit
      chemoconvulsant-induced epileptiform activity. Furthermore, this increase in KCC2
      function mitigated induction of aberrant high-frequency activity during seizures,
      highlighting depolarizing GABA as a key contributor to the pathological neuronal
      synchronization seen in epilepsy. Thus, our results demonstrate that potentiating
      KCC2 represents a therapeutic strategy to alleviate seizures.

PMID- 30224501
TI  - The utility of FDG-PET imaging in distinguishing PML-IRIS from PML in a patient
      treated with natalizumab.

PMID- 30224502
TI  - Journal Club: Florbetapir imaging in cerebral amyloid angiopathy-related
      hemorrhages.

PMID- 30224503
TI  - Editors' note: Pathologic Thr175 tau phosphorylation in CTE and CTE with ALS.

PMID- 30224504
TI  - Reader response: Pathologic Thr175 tau phosphorylation in CTE and CTE with ALS.

PMID- 30224505
TI  - Author response: Pathologic Thr175 tau phosphorylation in CTE and CTE with ALS.

PMID- 30224506
TI  - Editors' note: Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety
      findings.

PMID- 30224507
TI  - Reader response: Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety
      findings.

PMID- 30224508
TI  - Author response: Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety
      findings.

PMID- 30224509
TI  - Clinical Reasoning: Transient speech deficits in a patient with history of
      medulloblastoma.

PMID- 30224510
TI  - Teaching NeuroImages: Spinal intramedullary cysticercosis: The pseudotumoral
      form.

PMID- 30224511
TI  - Teaching Video NeuroImages: The signs of dystonic tremor: Tremulous
      "escanciador".

PMID- 30224512
TI  - Therapeutic Potential of Mesenchymal Cell-Derived miRNA-150-5p-Expressing
      Exosomes in Rheumatoid Arthritis Mediated by the Modulation of MMP14 and VEGF.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by
      synovial tissue inflammation and joint destruction associated with the activation
      of angiogenesis. Exosomes, which play a role in cell-to-cell communication as
      carriers of genetic information, transfer microRNAs (miRNAs or miRs) between
      cells and have been studied as delivery vehicles for therapeutic molecules. The
      aim of the current study was to investigate the therapeutic effect of mesenchymal
      stem cell (MSC)-derived miR-150-5p exosomes on joint destruction in RA. The
      expression and secretion of miR-150-5p, matrix metalloproteinase (MMP) 14, and
      vascular endothelial growth factor (VEGF) in RA patients and fibroblast-like
      synoviocytes (FLS) were examined by quantitative RT-PCR, ELISA, and Western
      blotting. Immunohistochemistry was used to assess angiogenesis. MSCs were
      transfected with an miR-150-5p expression plasmid, and MSC-derived exosomes were
      harvested. The effect of MSC-derived miR-150-5p exosomes (Exo-150) on MMP14 and
      VEGF expression was examined. The effects of Exo-150 on cell migration and
      invasion in cytokine-stimulated FLS from RA patients were examined by HUVEC tube
      formation and transwell assays. The effect of Exo-150 in vivo was examined in a
      collagen-induced arthritis mouse model. Exo-150 decreased migration and invasion
      in RA FLS and downregulated tube formation in HUVECs by targeting MMP14 and VEGF.
      Injection of Exo-150 reduced hind paw thickness and the clinical arthritic scores
      in collagen-induced arthritis mice. Exo-150 reduced joint destruction by
      inhibiting synoviocyte hyperplasia and angiogenesis. Exosomes facilitate the
      direct intracellular transfer of miRNAs between cells and represent a potential
      therapeutic strategy for RA.

PMID- 30224513
TI  - d-Glycero-beta-d-Manno-Heptose 1-Phosphate and d-Glycero-beta-d-Manno-Heptose 1,7
      Biphosphate Are Both Innate Immune Agonists.
AB  - d-Glycero-beta-d-manno-heptose 1,7-biphosphate (beta-HBP) is a novel microbial
      associated molecular pattern that triggers inflammation and thus has the
      potential to act as an immune modulator in many therapeutic contexts. To better
      understand the structure-activity relationship of this molecule, we chemically
      synthesized analogs of beta-HBP and tested their ability to induce canonical TIFA
      dependent inflammation in human embryonic kidney cells (HEK 293T) and colonic
      epithelial cells (HCT 116). Of the analogs tested, only d-glycero-beta-d-manno
      heptose 1-phosphate (beta-HMP) induced TIFA-dependent NF-kappaB activation and
      cytokine production in a manner similar to beta-HBP. This finding expands the
      spectrum of metabolites from the Gram-negative ADP-heptose biosynthesis pathway
      that can function as innate immune agonists and provides a more readily available
      agonist of the TIFA-dependent inflammatory pathway that can be easily produced by
      synthetic methods.

PMID- 30224514
TI  - IL-17A Attenuates IFN-lambda Expression by Inducing Suppressor of Cytokine
      Signaling Expression in Airway Epithelium.
AB  - IFN-lambda is a cytokine expressed in epithelial tissues and plays a central role
      in antiviral mucosal immune response. The expression of IFN-lambda in the airway
      is impaired in chronic airway diseases (e.g., asthma, chronic obstructive
      pulmonary disease), which renders patients susceptible to viral infection. IL-17A
      is associated with asthma and chronic obstructive pulmonary disease pathogenesis;
      however, IL-17A regulation of IFN-lambda expression remains unclear. The aim of
      the current study is to clarify IL-17A-mediated regulatory mechanisms of IFN
      lambda expression in human airway epithelial cells. In this study, we have shown
      that polyinosinic:polycytidylic acid (polyI:C) and influenza A virus (IAV)
      infection increased IFN-lambda expression at mRNA and protein levels in primary
      cultures of normal human bronchial epithelial cells, whereas IL-17A attenuated
      polyI:C- or IAV-induced IFN-lambda expression. IFN-lambda receptor 1 knockdown
      and a JAK inhibitor, ruxolitinib, attenuated polyI:C-induced IFN-lambda
      expression, confirming that a positive autocrine feedback loop, the IFN-lambda
      receptor-JAK-STAT pathway, was involved in IFN-lambda expression. In Western
      blotting analysis, we demonstrated that polyI:C and IAV infection induced STAT1
      phosphorylation in normal human bronchial epithelial cells, whereas IL-17A
      suppressed polyI:C- or IAV-mediated STAT1 phosphorylation. Furthermore, we found
      that cotreatment with IL-17A and polyI:C or IAV infection synergistically
      increased suppressor of cytokine signaling (SOCS)1 and SOCS3 expression. SOCS1
      small interfering RNA and SOCS3 small interfering RNA negated the inhibitory
      effect of IL-17A in polyI:C-induced IFN-lambda expression by restoring attenuated
      STAT1 phosphorylation. Taken together, these findings indicate that IL-17A
      attenuates virus-induced IFN-lambda expression by enhancing SOCS1 and SOCS3
      expression to inhibit autocrine signaling loops in human airway epithelial cells.

PMID- 30224515
TI  - Sixty seconds on . . . tokophobia.

PMID- 30224516
TI  - Native and Polyubiquitinated Forms of Dihydroceramide Desaturase Are
      Differentially Linked to Human Embryonic Kidney Cell Survival.
AB  - There is controversy concerning the role of dihydroceramide desaturase (Degs1) in
      regulating cell survival, with studies showing that it can both promote and
      protect against apoptosis. We have therefore investigated the molecular basis for
      these opposing roles of Degs1. Treatment of HEK293T cells with the sphingosine
      kinase inhibitor SKi [2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole] or
      fenretinide, but not the Degs1 inhibitor GT11 {N-[(1R,2S)-2-hydroxy-1
      hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octan-amide}, induced the
      polyubiquitination of Degs1 (M r = 40 to 140 kDa) via a mechanism involving
      oxidative stress, p38 mitogen-activated protein kinase (MAPK), and Mdm2 (E3
      ligase). The polyubiquitinated forms of Degs1 exhibit "gain of function" and
      activate prosurvival pathways, p38 MAPK, c-Jun N-terminal kinase (JNK), and X-box
      protein 1s (XBP-1s). In contrast, another sphingosine kinase inhibitor, ABC294640
      [3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide], at
      concentrations of 25 to 50 MUM failed to induce formation of the
      polyubiquitinated forms of Degs1. In contrast to SKi, ABC294640 (25 MUM) promotes
      apoptosis of HEK293T cells via a Degs1-dependent mechanism that is associated
      with increased de novo synthesis of ceramide. These findings are the first to
      demonstrate that the polyubiquitination of Degs1 appears to change its function
      from proapoptotic to prosurvival. Thus, polyubiquitination of Degs1 might provide
      an explanation for the reported opposing functions of this enzyme in cell
      survival/apoptosis.

PMID- 30224517
TI  - APOBEC3H Subcellular Localization Determinants Define Zipcode for Targeting HIV-1
      for Restriction.
AB  - APOBEC enzymes are DNA cytosine deaminases that normally serve as virus
      restriction factors, but several members, including APOBEC3H, also contribute to
      cancer mutagenesis. Despite their importance in multiple fields, little is known
      about cellular processes that regulate these DNA mutating enzymes. We show that
      APOBEC3H exists in two distinct subcellular compartments, cytoplasm and
      nucleolus, and that the structural determinants for each mechanism are
      genetically separable. First, native and fluorescently tagged APOBEC3Hs localize
      to these two compartments in multiple cell types. Second, a series of genetic,
      pharmacologic, and cell biological studies demonstrate active cytoplasmic and
      nucleolar retention mechanisms, whereas nuclear import and export occur through
      passive diffusion. Third, APOBEC3H cytoplasmic retention determinants relocalize
      APOBEC3A from a passive cell-wide state to the cytosol and, additionally, endow
      potent HIV-1 restriction activity. These results indicate that APOBEC3H has a
      structural zipcode for subcellular localization and selecting viral substrates
      for restriction.

PMID- 30224518
TI  - Deficiency of the Endocytic Protein Hip1 Leads to Decreased Gdpd3 Expression, Low
      Phosphocholine, and Kypholordosis.
AB  - Deficiency of huntingtin-interacting protein 1 (Hip1) results in degenerative
      phenotypes. Here we generated a Hip1 deficiency allele where a floxed
      transcriptional stop cassette and a human HIP1 cDNA were knocked into intron 1 of
      the mouse Hip1 locus. CMV-Cre-mediated germ line excision of the stop cassette
      resulted in expression of HIP1 and rescue of the Hip1 knockout phenotype. Mx1-Cre
      mediated excision led to HIP1 expression in spleen, kidney and liver, and also
      rescued the phenotype. In contrast, hGFAP-Cre-mediated, brain-specific HIP1
      expression did not rescue the phenotype. Metabolomics and microarrays of several
      Hip1 knockout tissues identified low phosphocholine (PC) levels and low
      glycerophosphodiester phosphodiesterase domain containing 3 (Gdpd3) gene
      expression. Since Gdpd3 has lysophospholipase D activity that results in the
      formation of choline, a precursor of PC, Gdpd3 downregulation could lead to the
      low PC levels. To test whether Gdpd3 contributes to the Hip1 deficiency
      phenotype, we generated Gdpd3 knockout mice. Double knockout of Gdpd3 and Hip1
      worsened the Hip1 phenotype. This suggests that Gdpd3 compensates for Hip1 loss.
      More-detailed knowledge of how Hip1 deficiency leads to low PC will improve our
      understanding of HIP1 in choline metabolism in normal and disease states.

PMID- 30224519
TI  - Human DnaJB6 Antiamyloid Chaperone Protects Yeast from Polyglutamine Toxicity
      Separately from Spatial Segregation of Aggregates.
AB  - Polyglutamine (polyQ) aggregates are associated with pathology in protein-folding
      diseases and with toxicity in the yeast Saccharomyces cerevisiae Protection from
      polyQ toxicity in yeast by human DnaJB6 coincides with sequestration of
      aggregates. Gathering of misfolded proteins into deposition sites by protein
      quality control (PQC) factors has led to the view that PQC processes protect
      cells by spatially segregating toxic aggregates. Whether DnaJB6 depends on this
      machinery to sequester polyQ aggregates, if this sequestration is needed for
      DnaJB6 to protect cells, and the identity of the deposition site are unknown.
      Here, we found DnaJB6-driven deposits share characteristics with perivacuolar
      insoluble protein deposition sites (IPODs). Binding of DnaJB6 to aggregates was
      necessary, but not enough, for detoxification. Focal formation required a DnaJB6
      Hsp70 interaction and actin, polyQ could be detoxified without sequestration, and
      segregation of aggregates alone was not protective. Our findings suggest DnaJB6
      binds to smaller polyQ aggregates to block their toxicity. Assembly and
      segregation of detoxified aggregates are driven by an Hsp70- and actin-dependent
      process. Our findings show sequestration of aggregates is not the primary
      mechanism by which DnaJB6 suppresses toxicity and raise questions regarding how
      and when misfolded proteins are detoxified during spatial segregation.

PMID- 30224520
TI  - Induction of hepatic metabolic functions by a novel variant of hepatocyte nuclear
      factor 4gamma.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) is a critical factor for hepatocyte
      differentiation. HNF4alpha expression is decreased in hepatocellular carcinoma
      (HCC), which suggests a role in repression of hepatocyte dedifferentiation. In
      the present study, hepatic expression of HNF4gamma was increased in liver
      specific Hnf4a-null mice. The increased HNF4gamma contained two variants, a known
      short variant, designated HNF4gamma1, and a novel long variant, designated
      HNF4gamma2. HNF4G2 mRNA was highly expressed in small intestine, and the
      transactivation potential of HNF4gamma2 was the strongest among these variants,
      but the potential of HNF4gamma1 was the lowest. Co-transfection experiments
      revealed that HNF4gamma1 repressed HNF4alpha- and HNF4gamma2-dependent
      transactivation while HNF4gamma2 promoted the HNF4alpha-dependent
      transactivation. HNF4gamma1 and HNF4gamma2 were able to bind to the HNF4alpha
      binding sites with similar affinity as HNF4alpha. Furthermore, HNF4gamma2, but
      not HNF4gamma1, robustly induced expression of typical HNF4alpha target genes to
      a greater degree than did HNF4alpha. Additionally, HNF4gamma2 suppressed
      proliferation of hepatoma cells as well as HNF4alpha and HNF4gamma1, and
      HNF4gamma2 induced critical hepatic functions such as glucose and urea
      production, and CYP1A2 activity stronger than did HNF4alpha and HNF4gamma1. These
      results indicate that HNF4gamma2 has potential for redifferentiation of HCC and
      thus may be explored as a target for HCC therapy.

PMID- 30224521
TI  - Expression of the Alternative Oxidase Influences Jun N-Terminal Kinase Signaling
      and Cell Migration.
AB  - Downregulation of Jun N-terminal kinase (JNK) signaling inhibits cell migration
      in diverse model systems. In Drosophila pupal development, attenuated JNK
      signaling in the thoracic dorsal epithelium leads to defective midline closure,
      resulting in cleft thorax. Here we report that concomitant expression of the
      Ciona intestinalis alternative oxidase (AOX) was able to compensate for JNK
      pathway downregulation, substantially correcting the cleft thorax phenotype. AOX
      expression also promoted wound-healing behavior and single-cell migration in
      immortalized mouse embryonic fibroblasts (iMEFs), counteracting the effect of JNK
      pathway inhibition. However, AOX was not able to rescue developmental phenotypes
      resulting from knockdown of the AP-1 transcription factor, the canonical target
      of JNK, nor its targets and had no effect on AP-1-dependent transcription. The
      migration of AOX-expressing iMEFs in the wound-healing assay was differentially
      stimulated by antimycin A, which redirects respiratory electron flow through AOX,
      altering the balance between mitochondrial ATP and heat production. Since other
      treatments affecting mitochondrial ATP did not stimulate wound healing, we
      propose increased mitochondrial heat production as the most likely primary
      mechanism of action of AOX in promoting cell migration in these various contexts.

PMID- 30224524
TI  - Low In Vitro Antifungal Activity of Tavaborole against Yeasts and Molds from
      Onychomycosis.
AB  - The in vitro activity of tavaborole, an FDA-approved antifungal drug, was
      compared to that of four antifungal agents against 170 clinical fungal isolates
      originating from patients with onychomycosis. Tavaborole had low activity against
      all isolates compared to itraconazole, terbinafine, and fluconazole, the
      principal choices for treatment of onychomycosis. Thus, it appears that
      tavaborole is not a candidate for the treatment of onychomycosis due to Candida
      species, Aspergillus species, and dermatophytes.

PMID- 30224525
TI  - Comparison of the Drug-Drug Interaction Potential of Daptomycin in Combination
      with Rifampin in Healthy Adult Volunteers.
AB  - We evaluated the effects of rifampin coadministration and MDR1 single nucleotide
      polymorphisms on the disposition of daptomycin in twelve healthy adults. There
      were no significant changes from baseline in the clearance (0.53 versus 0.55
      liters/h, P = 1.00), volume of distribution (7.0 versus 7.2 liter, P = 0.62), or
      half-life (9.7 versus 9.6 h, P = 0.89) of daptomycin after exposure to rifampin.
      The tested MDR1 polymorphisms were not associated with significant differences in
      daptomycin disposition.

PMID- 30224526
TI  - Intrahepatic Administration of Liposomal Amphotericin B (Ambisome) for the
      Management of a Liver Abscess from Candida albicans in a Preterm Infant.
AB  - Hepatic fungal abscesses are rare in the neonatal period and often constitute a
      severe complication of the catheterization of the umbilical vessels. Such life
      threatening lesions are observed more frequently in preterm than in other newborn
      infants and the optimal treatment remains uncertain. We present the case of a
      preterm neonate, who developed an intrahepatic lesion due to parenteral
      extravasation, successively contaminated by Candida albicans Despite the maximal
      pharmacological therapies, the treatment that led to the definitive resolution of
      the abscess was the placement of surgical drainage followed by the direct
      intralesional administration of liposomal amphotericin B (Ambisome), never
      described in neonates in the literature, which turned out to be a safe and
      effective approach.

PMID- 30224527
TI  - Synergistic Antimicrobial Activity of Colistin in Combination with Rifampin and
      Azithromycin against Escherichia coli Producing MCR-1.
AB  - The lack of available antibiotics is a global public health problem due to the
      emergence of antimicrobial resistance. Effective therapeutic regimens are
      urgently needed against Escherichia coli strains that produce the colistin
      resistance gene mcr-1 and to inhibit the emergence of resistance. In this study,
      we assessed the antimicrobial activity of a series of concentrations of colistin
      based combinations with rifampin and/or azithromycin against three strains of
      Escherichia coli, including colistin-resistant isolate MZ1501R, isolate HE1704R
      that produces MCR-1, and colistin-susceptible isolate MZ1509S Experiments were
      conducted with a medium inoculum of ~107 CFU/ml over 48 h. Subsequently, the in
      vivo therapeutic effect was investigated using a neutropenic mouse thigh
      infection model. Almost all monotherapies showed unsatisfactory antibacterial
      activity against E. coli isolates producing MCR-1. In contrast, colistin in
      combination with rifampin or azithromycin resulted in an obvious decrease in the
      bacterial burden albeit with regrowth. More obviously, synergistic antimicrobial
      activity of colistin-based triple-combination therapy with rifampin and
      azithromycin was observed, resulting in a rapid and exhaustive antibacterial
      effect. In vivo treatments confirmed these findings, where mean decreases of 0.38
      to 0.90 log10 CFU and 1.27 to 1.78 log10 CFU were noted after 24 h and 48 h of
      treatment, respectively, against colistin-resistant E. coli strains when 5 mg/kg
      of body weight of colistin was combined with rifampin and azithromycin. Colistin
      based combinations with rifampin and azithromycin provide a more active
      therapeutic regimen than monotherapy or colistin-based double combinations
      against E. coli producing MCR-1.

PMID- 30224528
TI  - Identification and Characterization of IncA/C Conjugative, bla NDM-1-Bearing
      Plasmid in Vibrio alginolyticus of Food Origin.

PMID- 30224529
TI  - A Randomized Study of the Single-Dose Safety, Pharmacokinetics, and Food Effect
      of Chinfloxacin and Its Effect on Thorough QT/QTc Interval in Healthy Chinese
      Volunteers.
AB  - Chinfloxacin hydrochloride is a novel tricyclic fluorinated quinolone in
      development for treatment of conventional and biothreat infections. This first-in
      human randomized study in Chinese healthy subjects was divided into 5 parts. Part
      A was a single-ascending-dose study to assess safety and tolerability of
      chinfloxacin. The single-dose pharmacokinetic study, a food effect study, and a
      multiple-dose pharmacokinetics study were conducted in parts B, C, and D,
      respectively. Part E was a randomized, placebo-controlled and positive-control
      single-dose, crossover study to evaluate the effect of chinfloxacin on thorough
      electrocardiographic QT/corrected QT (QTc) interval. The results suggest that
      single and multiple oral administrations of chinfloxacin were well tolerated. The
      observed adverse events (AEs) were dizziness, nausea, weakness, photosensitive
      dermatitis, and increased frequency of defecation. All AEs were mild and were
      resolved spontaneously without any treatment. The time to peak plasma
      concentration (T max and C max, respectively) was about 2 h, and the half-life
      was 14 to 16 h. Food slightly affected the drug's rate and extent of absorption,
      increasing the T max from 1.60 to 2.59 h and reducing the C max by 13.6% and area
      under the concentration-time curve by 8.95%. Chinfloxacin at 400 mg had no effect
      on prolongation of QT/QTc intervals. Although 600 mg chinfloxacin had a mild
      effect on the prolongation of the QT/QTc interval, the effect was less pronounced
      than that of the positive control, 400 mg moxifloxacin. The pharmacokinetics and
      safety profiles of chinfloxacin in healthy Chinese volunteers support its once
      daily dosing in future clinical investigations. (This study has been registered
      at www.ChiCTR.org.cn under identifiers ChiCTR-TRC-10001619 for parts A to D and
      ChiCTR1800015906 for part E.).

PMID- 30224530
TI  - Gametocytes from K13 Propeller Mutant Plasmodium falciparum Clinical Isolates
      Demonstrate Reduced Susceptibility to Dihydroartemisinin in the Male Gamete
      Exflagellation Inhibition Assay.
AB  - Mutations in the kelch propeller domain (K13 propeller) of Plasmodium falciparum
      parasites from Southeast Asia are associated with reduced susceptibility to
      artemisinin. We exposed in vitro-cultured stage V gametocytes from Cambodian K13
      propeller mutant parasites to dihydroartemisinin and evaluated the inhibition of
      male gamete formation in an in vitro exflagellation inhibition assay (EIA).
      Gametocytes with the R539T and C580Y K13 propeller alleles were less susceptible
      to dihydroartemisinin and had significantly higher 50% inhibitory concentrations
      (IC50s) than did gametocytes with wild-type alleles.

PMID- 30224531
TI  - Identification of Compounds Targeting Hepatitis B Virus Core Protein Dimerization
      through a Split Luciferase Complementation Assay.
AB  - The capsid of the hepatitis B virus is an attractive antiviral target for
      developing therapies against chronic hepatitis B infection. Currently available
      core protein allosteric modulators (CpAMs) mainly affect one of the two major
      types of protein-protein interactions involved in the process of capsid assembly,
      namely, the interaction between the core dimers. Compounds targeting the
      interaction between two core monomers have not been rigorously screened due to
      the lack of screening models. We report here a cell-based assay in which the
      formation of core dimers is indicated by split luciferase complementation (SLC).
      Making use of this model, 2 compounds, Arbidol (umifenovir) and 20-deoxyingenol,
      were identified from a library containing 672 compounds as core dimerization
      regulators. Arbidol and 20-deoxyingenol inhibit the hepatitis B virus (HBV) DNA
      replication in vitro by decreasing and increasing the formation of core dimer and
      capsid, respectively. Our results provided a proof of concept for the cell model
      to be used to screen new agents targeting the step of core dimer and capsid
      formation.

PMID- 30224532
TI  - Synthesis, Biological Evaluation, and Molecular Modeling Studies of Chiral
      Chloroquine Analogues as Antimalarial Agents.
AB  - In a focused exploration, we designed, synthesized, and biologically evaluated
      chiral conjugated new chloroquine (CQ) analogues with substituted piperazines as
      antimalarial agents. In vitro as well as in vivo studies revealed that compound
      7c showed potent activity (in vitro 50% inhibitory concentration, 56.98 nM for
      strain 3D7 and 97.76 nM for strain K1; selectivity index in vivo [up to at a dose
      of 12.5 mg/kg of body weight], 3,510) as a new lead antimalarial agent. Other
      compounds (compounds 6b, 6d, 7d, 7h, 8c, 8d, 9a, and 9c) also showed moderate
      activity against a CQ-sensitive strain (3D7) and superior activity against a CQ
      resistant strain (K1) of Plasmodium falciparum Furthermore, we carried out
      docking and three-dimensional quantitative structure-activity relationship (3D
      QSAR) studies of all in-house data sets (168 molecules) of chiral CQ analogues to
      explain the structure-activity relationships (SAR). Our new findings specify the
      significance of the H-bond interaction with the side chain of heme for biological
      activity. In addition, the 3D-QSAR study against the 3D7 strain indicated the
      favorable and unfavorable sites of CQ analogues for incorporating steric,
      hydrophobic, and electropositive groups to improve the antimalarial activity.

PMID- 30224533
TI  - Double-Blind, Randomized, Placebo-Controlled Phase II Dose-Finding Study To
      Evaluate High-Dose Rifampin for Tuberculous Meningitis.
AB  - High doses of rifampin may help patients with tuberculous meningitis (TBM) to
      survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin
      doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as
      previously studied) are warranted to maximize treatment response. In a double
      blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM
      patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20,
      and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days. The
      endpoints included pharmacokinetic measures, adverse events, and survival. A
      double and triple dose of oral rifampin led to 3- and 5-fold higher geometric
      mean total exposures in plasma in the critical early days (2 +/- 1) of treatment
      (area under the concentration-time curve from 0 to 24 h [AUC0-24], 53.5 mg .
      h/liter versus 170.6 mg . h/liter and 293.5 mg . h/liter, respectively; P <
      0.001), with proportional increases in cerebrospinal fluid (CSF) concentrations
      and without an increase in the incidence of grade 3 or 4 adverse events. The 6
      month mortality was 7/20 (35%), 9/20 (45%), and 3/20 (15%) in the 10-, 20-, and
      30-mg/kg groups, respectively (P = 0.12). A tripling of the standard dose caused
      a large increase in rifampin exposure in plasma and CSF and was safe. The
      survival benefit with this dose should now be evaluated in a larger phase III
      clinical trial. (This study has been registered at ClinicalTrials.gov under
      identifier NCT02169882.).

PMID- 30224534
TI  - Comparative Epidemiology of Vancomycin-Resistant Enterococci Colonization in an
      Acute-Care Hospital and Its Affiliated Intermediate- and Long-Term Care
      Facilities in Singapore.
AB  - Vancomycin-resistant enterococci (VRE) are an important cause of nosocomial
      infections in acute-care hospitals (ACHs), intermediate-care facilities (ITCFs),
      and long-term care facilities (LTCFs). This study contemporaneously compared the
      epidemiology and risk factors for VRE colonization in different care settings in
      a health care network. We conducted a serial cross-sectional study in a 1,700-bed
      ACH and its six closely affiliated ITCFs and LTCFs in June and July of 2014 to
      2016. Rectal swab or stool specimens were cultured for VRE. Multivariable
      logistic regression was used to assess for independent risk factors associated
      with VRE colonization. Of 5,357 participants, 523 (9.8%) were VRE colonized. VRE
      prevalence was higher in ACHs (14.2%) than in ITCFs (7.6%) and LTCFs (0.8%).
      Common risk factors between ACHs and ITCFs included prior VRE carriage, a longer
      duration of antibiotic therapy, surgery in the preceding 90 days, and the
      presence of a skin ulcer. Independent risk factors specific to ACH-admitted
      patients were prior methicillin-resistant Staphylococcus aureus carriage, a
      higher number of beds per room, prior proton pump inhibitor use, and a length of
      stay of >14 days. For ITCFs, a length of stay of >14 days was inversely
      associated with VRE colonization. Similarities and differences in risk factors
      for VRE colonization were observed between health care settings. VRE prevention
      efforts should target the respective high-risk patients.

PMID- 30224535
TI  - Antimicrobial Susceptibility of Pseudomonas aeruginosa to Ceftazidime-Avibactam,
      Ceftolozane-Tazobactam, Piperacillin-Tazobactam, and Meropenem Stratified by U.S.
      Census Divisions: Results from the 2017 INFORM Program.
AB  - Pseudomonas aeruginosa isolates (n = 1,909) were collected from 70 U.S. medical
      centers, and their susceptibilities were tested using the broth microdilution
      method. Ceftazidime-avibactam (MIC50/MIC90, 2/8 mg/liter) and ceftolozane
      tazobactam (MIC50/MIC90, 0.5/2 mg/liter) were the most active (i.e., had the
      highest susceptibility rates) compounds after colistin, with national
      susceptibility rates of 96.9% and 97.5%, respectively. Overall, piperacillin
      tazobactam (MIC50/MIC90, 4/128 mg/liter) and meropenem (MIC50/MIC90, 0.5/16
      mg/liter) were active against 77.5% and 76.0% of the isolates, respectively.
      Susceptibility variations across census divisions were documented for many
      antimicrobials.

PMID- 30224536
TI  - Identification of Retinoic Acid Receptor Agonists as Potent Hepatitis B Virus
      Inhibitors via a Drug Repurposing Screen.
AB  - Currently available therapies for chronic hepatitis B virus (HBV) infection can
      efficiently reduce viremia but induce hepatitis B surface antigen (HBsAg) loss in
      very few patients; also, these therapies do not greatly affect the viral
      covalently closed circular DNA (cccDNA). To discover new agents with
      complementary anti-HBV effects, we performed a drug repurposing screen of 1,018
      Food and Drug Administration (FDA)-approved compounds using HBV-infected primary
      human hepatocytes (PHH). Several compounds belonging to the family of retinoic
      acid receptor (RAR) agonists were identified that reduced HBsAg levels in a dose
      dependent manner without significant cytotoxicity. Among them, tazarotene
      exhibited the most potent anti-HBV effect, with a half-maximal inhibitory
      concentration (IC50) for HBsAg of less than 30 nM in PHH. The inhibitory effect
      was also observed in HBV-infected differentiated HepaRG (dHepaRG) models, but not
      in HepG2.215 cells, and HBV genotypes A to D were similarly inhibited. Tazarotene
      was further demonstrated to repress HBV cccDNA transcription, as determined by
      the levels of HBV cccDNA and RNAs and the activation of HBV promoters. Moreover,
      RNA sequence analysis showed that tazarotene did not induce an interferon
      response but altered the expression of a number of genes associated with RAR and
      metabolic pathways. Inhibition of RARbeta, but not RARalpha, by a specific
      antagonist significantly attenuated the anti-HBV activity of tazarotene,
      suggesting that tazarotene inhibits HBV in part through RARbeta. Finally, a
      synergistic effect of tazarotene and entecavir on HBV DNA levels was observed.
      Therefore, RAR agonists as represented by tazarotene were identified as potential
      novel anti-HBV agents.

PMID- 30224537
TI  - Beyond Penicillin: Rapid Desensitization for Specific Flucloxacillin
      Hypersensitivity.
AB  - Beta-lactam therapy for severe staphylococcal infections is associated with
      superior outcomes, compared to non-beta-lactam therapy. For patients with
      immediate hypersensitivity to beta-lactams, desensitization has been widely
      employed to allow beta-lactam therapy, but published protocols for
      antistaphylococcal beta-lactams such as flucloxacillin are lacking. Here, we
      report a case and describe the desensitization protocol successfully used for a
      patient with isolated flucloxacillin immediate hypersensitivity, for whom a
      penicillin desensitization protocol would likely have resulted in an adverse drug
      reaction.

PMID- 30224538
TI  - Implications of the EUCAST Trailing Phenomenon in Candida tropicalis for the In
      Vivo Susceptibility in Invertebrate and Murine Models.
AB  - Candida tropicalis isolates often display reduced but persistent growth
      (trailing) over a broad fluconazole concentration range during EUCAST
      susceptibility testing. Whereas weak trailing (<25% of the positive growth
      control) is common and found not to impair fluconazole efficacy, we investigated
      if more pronounced trailing impacted treatment efficacy. Fluconazole efficacy
      against two weakly (<=25% growth), two moderately (26% to 50% growth), and one
      heavily (>70% growth) trailing resistant isolate and one resistant (100% growth)
      isolate were investigated in vitro and in vivo (in a Galleria mellonella survival
      model and two nonlethal murine models). CDR1 expression levels and ERG11
      sequences were characterized. The survival in fluconazole-treated G. mellonella
      was inversely correlated with the degree of trailing (71% to 9% survival in
      treatment groups). In mice, resistant and heavily trailing isolates responded
      poorly to fluconazole treatment. CDR1 expression was significantly higher in
      trailing and resistant isolates than in wild-type isolates (1.4-fold to 10-fold
      higher). All isolates exhibited ERG11 wild-type alleles. Heavily trailing
      isolates were less responsive to fluconazole in all in vivo models, indicating an
      impact on fluconazole efficacy. CDR1 upregulation may have contributed to the
      observed differences. Moderately trailing isolates responded less well to
      fluconazole in larvae only. This confirms clinical data suggesting fluconazole is
      effective against infections with such isolates in less severely ill patients and
      supports the current 50% growth endpoint for susceptibility testing. However, it
      is still unclear if the gradual loss of efficacy observed for moderately trailing
      isolates in the larva model may be a reason for concern in selected vulnerable
      patient populations.

PMID- 30224539
TI  - Lung-Enriched Mutations in the p53 Tumor Suppressor: A Paradigm for Tissue
      Specific Gain of Oncogenic Function.
AB  - Lung cancer, the leading cause of cancer-related mortality in the United States,
      occurs primarily due to prolonged exposure to an array of carcinogenic compounds
      in cigarette smoke. These carcinogens create bulky DNA adducts, inducing
      alterations including missense mutations in the tumor suppressor gene TP53 TP53
      is the most commonly mutated gene in many human cancers, and a specific set of
      these variants are enriched in lung cancer (at amino acid residues V157, R158,
      and A159). This perspective postulates that lung-enriched mutations can be
      explained, in part, by biological selection for oncogenic gain-of-function (GOF)
      mutant p53 alleles at V157, R158, and A159. This hypothesis explaining tissue
      specific TP53 mutations is further supported by mouse model studies of the
      canonical TP53 hotspots showing that tumor spectra and GOF activities are altered
      with mutation type. Therefore, although smoking-related lung cancer unequivocally
      arises due to the mutagenic environment induced by tobacco carcinogens, this
      perspective provides a rationale for the preferential selection of lung-enriched
      V157, R158, and A159 mutant p53. Mol Cancer Res; 1-7. (c)2018 AACR.

PMID- 30224540
TI  - A Novel Approach for Image-Guided 131I Therapy of Pancreatic Ductal
      Adenocarcinoma Using Mesenchymal Stem Cell-Mediated NIS Gene Delivery.
AB  - The sodium iodide symporter (SLC5A5/NIS) as theranostic gene would allow for non
      invasive imaging of functional NIS expression and therapeutic radioiodine
      application. Genetically engineered mesenchymal stem cells (MSC), based on their
      tumor-homing abilities, show great promise as tumor-selective NIS gene delivery
      vehicles for non-thyroidal tumors. As a next step towards clinical application,
      tumor specificity and efficacy of MSCs were investigated in an advanced
      genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC).
      Syngeneic murine MSCs were stably transfected with a NIS-expressing plasmid
      driven by the CMV-promoter (NIS-MSC). In vivo 123I-scintigraphy and 124I-PET
      revealed significant perchlorate-sensitive NIS-mediated radioiodide accumulation
      in PDAC after systemic injection of NIS-MSCs. Active MSC recruitment into the
      tumor stroma was confirmed using NIS immunohistochemistry (IHC). A therapeutic
      strategy, consisting of three cycles of systemic MSC-mediated NIS delivery,
      followed by 131I application, resulted in a significant delay and reduction in
      tumor growth as compared to controls. Furthermore, IHC analysis of alpha-SMA and
      Ki67 revealed differences in the amount and behavior of activated fibroblasts in
      tumors of mice injected with NIS-MSCs as compared with saline-treated mice. Taken
      together, MSCs as NIS gene delivery vehicles in this advanced endogenous PDAC
      mouse model demonstrated high stromal targeting of NIS by selective recruitment
      of NIS-MSCs after systemic application resulting in an impressive 131I
      therapeutic effect.Implications: These data expand the prospect of MSC-mediated
      radioiodine imaging-guided therapy of pancreatic cancer using the sodium iodide
      symporter as a theranostic gene in a clinical setting. Mol Cancer Res; 1-11.
      (c)2018 AACR.

PMID- 30224541
TI  - p53 Function is Compromised by Inhibitor 2 of Phosphatase 2A in Sonic Hedgehog
      Medulloblastoma.
AB  - Medulloblastomas, the most common malignant pediatric brain tumors, have been
      genetically defined into four subclasses, namely WNT-activated, Sonic Hedgehog
      (SHH)-activated, Group 3, and Group 4. Approximately 30% of medulloblastomas have
      aberrant SHH signaling and thus are referred to as SHH-activated medulloblastoma.
      The tumor suppressor gene TP53 has been recently recognized as a prognostic
      marker for patients with SHH-activated medulloblastoma; patients with mutant TP53
      have a significantly worse outcome than those with wild-type TP53. It remains
      unknown whether p53 activity is impaired in SHH-activated, wild-type TP53
      medulloblastoma, which is about 80% of the SHH-activated medulloblastomas.
      Utilizing the homozygous NeuroD2:SmoA1 mouse model with wild-type Trp53, which
      recapitulates human SHH-activated medulloblastoma, it was discovered that the
      endogenous Inhibitor 2 of Protein Phosphatase 2A (SET/I2PP2A) suppresses p53
      function by promoting accumulation of phospho-MDM2 (S166), an active form of MDM2
      that negatively regulates p53. Knockdown of I2PP2A in SmoA1 primary
      medulloblastoma cells reduced viability and proliferation in a p53-dependent
      manner, indicating the oncogenic role of I2PP2A. Importantly, this mechanism is
      conserved in the human medulloblastoma cell line ONS76 with wild-type TP53. Taken
      together, these findings indicate that p53 activity is inhibited by I2PP2A
      upstream of PP2A in SHH-activated and TP53-wildtype
      medulloblastomas.Implications: This study suggests that I2PP2A represents a novel
      therapeutic option and its targeting could improve the effectiveness of current
      therapeutic regimens for SHH-activated or other subclasses of medulloblastoma
      with wild-type TP53. Mol Cancer Res; 1-13. (c)2018 AACR.

PMID- 30224542
TI  - Establishment and Genetic Landscape of Precancer Cell Model Systems from the Head
      and Neck Mucosal Lining.
AB  - Head and neck squamous cell carcinomas (HNSCC) develop in fields of genetically
      altered cells. These fields are often dysplastic and a subset can be recognized
      as (erythro)leukoplakia, but most are macroscopically invisible. There is a lack
      of adequate treatment options to eradicate these fields, whereas they underlie
      the development of primary tumors as well as part of the local relapses.
      Unfortunately, there are almost no representative cellular models available to
      identify suitable treatment options. To this end, clinical biopsy specimens (n =
      98) were cultured from normal appearing mucosa of the surgical margins of
      patients with primary HNSCCs (n = 32) to generate precancer cell culture models.
      This collection was extended with six previously established precancer cell
      cultures. Genetic analysis was performed on cultures with an extended life span
      (>=20 population doublings), the previously established cultures, and some
      randomly selected cultures. In total, cancer-associated changes were detected in
      18 out of 34 (53%) cultures analyzed, which appeared to be independent of life
      span. A variety of genetic changes were identified, including somatic mutations
      as well as chromosomal copy-number aberrations (CNA). Loss of CDKN2A/p16Ink4A and
      mutations in TP53/p53 were most prominent. Remarkably, in some of these precancer
      cell cultures only chromosomal CNAs were detected, and none of the frequently
      occurring driver mutations.Implications: The precancer cell cultures,
      characterized herein, form a representative collection of field models that can
      be exploited to identify and validate new therapeutic strategies to prevent
      primary HNSCCs and local relapses. Mol Cancer Res; 1-11. (c)2018 AACR.

PMID- 30224543
TI  - The Role of Alcohol-induced Golgi Fragmentation for Androgen Receptor Signaling
      in Prostate Cancer.
AB  - Multiple epidemiologic observations and meta-analysis clearly indicate the link
      between alcohol abuse and the incidence and progression of prostate cancer;
      however, the mechanism remains enigmatic. Recently, it was found that ethanol
      (EtOH) induces disorganization of the Golgi complex caused by impaired function
      of the largest Golgi matrix protein, giantin (GOLGB1), which, in turn, alters the
      Golgi docking of resident Golgi proteins. Here, it is determined that in normal
      prostate cells, histone deacetylase 6 (HDAC6), the known regulator of androgen
      receptor (AR) signaling, localizes in the cytoplasm and nucleus, while its
      kinase, glycogen synthase kinase beta (GSK3beta), primarily resides in the Golgi.
      Progression of prostate cancer is accompanied by Golgi scattering, translocation
      of GSK3beta from the Golgi to the cytoplasm, and the cytoplasmic shift in HDAC6
      localization. Alcohol dehydrogenase-generated metabolites induces Golgi
      disorganization in androgen-responsive LNCaP and 22Rv1 cells, facilitates tumor
      growth in a mouse xenograft model and activates anchorage-independent
      proliferation, migration, and cell adhesion. EtOH-treated cells demonstrate
      reduced giantin and subsequent cytoplasmic GSK3beta; this phenomenon was
      validated in giantin-depleted cells. Redistribution of GSK3beta to the cytoplasm
      results in phosphorylation of HDAC6 and its retention in the cytoplasm, which, in
      turn, stimulates deacetylation of HSP90, AR import into the nucleus, and
      secretion of prostate-specific antigen (PSA). Finally, the relationship between
      Golgi morphology, HDAC6 cytoplasmic content, and clinicopathologic features was
      assessed in human prostate cancer patient specimens with and without a history of
      alcohol dependence.Implications: This study demonstrates the importance of
      alcohol-induced Golgi fragmentation in the activation of AR-mediated
      proliferation. Mol Cancer Res; 1-13. (c)2018 AACR.

PMID- 30224544
TI  - Targeting the MIF/CXCR7/AKT Signaling Pathway in Castration-Resistant Prostate
      Cancer.
AB  - Although androgen deprivation therapy (ADT) is an effective treatment for
      metastatic prostate cancer, incurable castration-resistant prostate cancer (CRPC)
      inevitably develops. Importantly, androgen receptor (AR) continues to be critical
      for prostate cancer growth and progression after ADT. One of the underlying
      molecular mechanisms is derepression of AR-repressed genes involved in cell cycle
      and proliferation after ADT. Here, the data demonstrate that C-X-C chemokine
      receptor type 7 (CXCR7), a seven-transmembrane G-protein-coupled chemokine
      receptor, is an AR-repressed gene and is upregulated after ADT. AR directly
      regulates CXCR7 using clustered regularly interspaced short palindromic
      repeats/CRISPR-associated protein 9 (CRISPR/Cas9) gene editing. Macrophage
      migration inhibitory factor (MIF) was identified as a ligand for CXCR7, which
      induces expression of cell-cycle genes through activating AKT signaling pathway.
      Previous studies have been focused on chemokine CXCL12 and its receptor CXCR4 in
      mediating metastasis of various cancer types, including prostate cancer. The
      critical roles of CXCL12/CXCR4 axis in the interaction between cancer cells and
      their microenvironment render it a promising therapeutic target in cancer
      treatment. The data suggest that the MIF/CXCR7/AKT pathway drives CRPC growth and
      metastasis independent of the CXCL12/CXCR4 axis. Furthermore, CXCR7 blockade in
      combination with anti-androgen enzalutamide inhibits CRPC tumor growth and
      potentially prevents metastasis. Notably, both MIF and CXCR7 are overexpressed in
      CRPC patient specimens and therefore are attractive therapeutic targets for these
      patients.Implications: This work suggests that CXCR7 plays more important roles
      than CXCR4 in CRPC progression; thus, targeting CXCR7 in combination with anti
      androgen is a promising therapeutic approach for metastatic CRPC. Mol Cancer Res;
      1-14. (c)2018 AACR.

PMID- 30224545
TI  - The Aged Microenvironment Influences the Tumorigenic Potential of Malignant
      Prostate Epithelial Cells.
AB  - The incidence of prostate cancer is directly linked to age, but age-associated
      changes that facilitate prostate cancer development and progression are poorly
      understood. This study investigated age-related changes in the prostate
      microenvironment for their influence on prostate cancer behavior. Prostate cancer
      cells implanted orthotopically into the prostate demonstrated accelerated tumor
      growth in aged compared with young mice. Metastatic lesions following intravenous
      injection were also more numerous in aged mice. Tumors from young and aged mice
      showed no significant differences concerning their proliferation index,
      apoptosis, or angiogenesis. However, analysis of tumor-infiltrating immune cells
      by IHC and RNA sequencing (RNA-seq) revealed elevated numbers of macrophages in
      prostates from aged mice, which are quickly polarized towards a phenotype
      resembling protumorigenic tumor-associated macrophages upon tumor cell
      engraftment. Older patients with prostate cancer (>60 years old) in The Cancer
      Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset displayed higher
      expression of macrophage markers (CD163 and VSIG4) which associated with higher
      rates of biochemical relapse. Remodeling of the collagenous extracellular matrix
      (ECM) was associated with prostate cancer growth and invasion in the aged
      microenvironment. Moreover, the collagen matrix extracted from aged mice enhanced
      the invasiveness and proliferation of prostate cancer cells in vitro Together,
      these results demonstrate that the aged prostatic microenvironment can regulate
      the growth and metastasis of malignant prostate cells, highlighting the role of
      resident macrophages and their polarization towards a protumorigenic phenotype,
      along with remodeling of the ECM.Implications: These findings demonstrate the
      importance of age-associated tumor microenvironment alterations in regulating key
      aspects of prostate cancer progression. Mol Cancer Res; 1-11. (c)2018 AACR.

PMID- 30224546
TI  - Advancing into the details of pulmonary haemodynamics during exercise.

PMID- 30224547
TI  - Differences in inflammatory profiles between ALS and FTD.

PMID- 30224548
TI  - Pain and the immune system: emerging concepts of IgG-mediated autoimmune pain and
      immunotherapies.
AB  - The immune system has long been recognised important in pain regulation through
      inflammatory cytokine modulation of peripheral nociceptive fibres. Recently,
      cytokine interactions in brain and spinal cord glia as well as dorsal root
      ganglia satellite glia have been identified important- in pain modulation. The
      result of these interactions is central and peripheral sensitisation of
      nociceptive processing. Additionally, new insights and the term 'autoimmune pain'
      have emerged through discovery of specific IgGs targeting the extracellular
      domains of antigens at nodal and synaptic structures, causing pain directly
      without inflammation by enhancing neuronal excitability. Other discovered IgGs
      heighten pain indirectly by T-cell-mediated inflammation or destruction of
      targets within the nociceptive pathways. Notable identified IgGs in pain include
      those against the components of channels and receptors involved in inhibitory or
      excitatory somatosensory synapses or their pathways: nodal and paranodal proteins
      (LGI1, CASPR1, CASPR2); glutamate detection (AMPA-R); GABA regulation and release
      (GAD65, amphiphysin); glycine receptors (GLY-R); water channels (AQP4). These
      disorders have other neurological manifestations of central/peripheral
      hyperexcitabability including seizures, encephalopathy, myoclonus, tremor and
      spasticity, with immunotherapy responsiveness. Other pain disorders, like complex
      regional pain disorder, have been associated with IgGs against beta2-adrenergic
      receptor, muscarinic-2 receptors, AChR-nicotinic ganglionic alpha-3 receptors and
      calcium channels (N and P/Q types), but less consistently with immune treatment
      response. Here, we outline how the immune system contributes to development and
      regulation of pain, review specific IgG-mediated pain disorders and summarise
      recent development in therapy approaches. Biological agents to treat pain (anti
      calcitonin gene-related peptide and anti-nerve growth factor) are also discussed.

PMID- 30224549
TI  - Different neuroinflammatory profile in amyotrophic lateral sclerosis and
      frontotemporal dementia is linked to the clinical phase.
AB  - OBJECTIVE: To investigate the role of neuroinflammation in asymptomatic and
      symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
      mutation carriers. METHODS: The neuroinflammatory markers chitotriosidase 1
      (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in
      cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic
      ALS/FTD mutation carriers, sporadic cases and controls by ELISA. RESULTS: CSF
      levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation
      carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas
      GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower
      CHIT1 concentrations in CSF (-80%) whereas this polymorphism had no influence on
      disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed
      (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and
      gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood
      concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30,
      GFAP, r=0.39). Blood concentrations of these three markers were not significantly
      altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05).
      CONCLUSION: Our data indicate that neuroinflammation is linked to the symptomatic
      phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS
      and FTD are characterised by a different neuroinflammatory profile, which might
      be one driver of the diverse presentations of the ALS/FTD syndrome.

PMID- 30224550
TI  - Does moderate alcohol consumption really have health benefits?

PMID- 30224551
TI  - Heterogeneity in FoxP3- and GARP/LAP-Expressing T Regulatory Cells in an HLA
      Class II Transgenic Murine Model of Necrotizing Soft Tissue Infections by Group A
      Streptococcus.
AB  - Invasive group A streptococcus (GAS) infections include necrotizing soft tissue
      infections (NSTI) and streptococcal toxic shock syndrome (STSS). We have
      previously shown that host HLA class II allelic variations determine the risk for
      necrotizing fasciitis (NF), a dominant subgroup of NSTI, and STSS by modulating
      responses to GAS superantigens (SAgs). SAgs are pivotal mediators of uncontrolled
      T-cell activation, triggering a proinflammatory cytokine storm in the host. FoxP3
      expressing CD4+ CD25+ T regulatory cells (Tregs) comprise phenotypically and
      functionally heterogeneous subsets with a profound ability to suppress
      inflammatory responses. Specifically, activated Tregs, which express glycoprotein
      A repetitions predominant (GARP) and display latent transforming growth factor
      beta1 (TGF-beta1) complexes (latency-associated peptide [LAP]), exhibit strong
      immunosuppressive functions. The significance of Tregs that may participate in
      suppressing inflammatory responses during NSTI is unknown. Here, we
      phenotypically characterized FoxP3/GARP/LAP-expressing Tregs in GAS-infected or
      SAg (SmeZ)-stimulated splenocytes from transgenic (tg) mice expressing human HLA
      II DRB1*15 (DR15 allele associated with nonsevere NF/STSS-protective responses)
      or DRB1*0402/DQB1*0302 (DR4/DQ8 alleles associated with neutral risk for combined
      NF/STSS). We demonstrated both in vivo and in vitro that the neutral-risk allele
      upregulates expression of CD4+ CD25+ activated effector T cells, with a
      significantly lower frequency of Foxp3+/GARP+ LAP- but higher frequency of Foxp3-
      LAP+ Tregs than seen with the protective allele. Additional in vitro studies
      revealed that the presentation of SmeZ by the neutral-risk allele significantly
      increases proliferation and expression of effector cytokines gamma interferon
      (IFN-gamma) and interleukin-2 (IL-2) and upregulates CD4+ CD25+ T cell receptors
      (TCRs) carrying specific Vbeta 11 chain (TCRVbeta11+) T cells and Th1
      transcription factor Tbx21 mRNA levels. Our data suggest that neutral-risk
      alleles may drive Th1 differentiation while attenuating the induction of Tregs
      associated with suppressive function.

PMID- 30224552
TI  - Preexisting Simian Immunodeficiency Virus Infection Increases Susceptibility to
      Tuberculosis in Mauritian Cynomolgus Macaques.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading cause of
      death among human immunodeficiency virus (HIV)-positive patients. The precise
      mechanisms by which HIV impairs host resistance to a subsequent M. tuberculosis
      infection are unknown. We modeled this coinfection in Mauritian cynomolgus
      macaques (MCM) using simian immunodeficiency virus (SIV) as an HIV surrogate. We
      infected seven MCM with SIVmac239 intrarectally and 6 months later coinfected
      them via bronchoscope with ~10 CFU of M. tuberculosis Another eight MCM were
      infected with M. tuberculosis alone. TB progression was monitored by clinical
      parameters, by culturing bacilli in gastric and bronchoalveolar lavages, and by
      serial [18F]fluorodeoxyglucose (FDG) positron emission tomography/computed
      tomography (PET/CT) imaging. The eight MCM infected with M. tuberculosis alone
      displayed dichotomous susceptibility to TB, with four animals reaching humane
      endpoint within 13 weeks and four animals surviving >19 weeks after M.
      tuberculosis infection. In stark contrast, all seven SIV+ animals exhibited
      rapidly progressive TB following coinfection and all reached humane endpoint by
      13 weeks. Serial PET/CT imaging confirmed dichotomous outcomes in MCM infected
      with M. tuberculosis alone and marked susceptibility to TB in all SIV+ MCM.
      Notably, imaging revealed a significant increase in TB granulomas between 4 and 8
      weeks after M. tuberculosis infection in SIV+ but not in SIV-naive MCM and
      implies that SIV impairs the ability of animals to contain M. tuberculosis
      dissemination. At necropsy, animals with preexisting SIV infection had more
      overall pathology, increased bacterial loads, and a trend towards more
      extrapulmonary disease than animals infected with M. tuberculosis alone. We thus
      developed a tractable MCM model in which to study SIV-M. tuberculosis coinfection
      and demonstrate that preexisting SIV dramatically diminishes the ability to
      control M. tuberculosis coinfection.

PMID- 30224553
TI  - Ceftriaxone Administration Disrupts Intestinal Homeostasis, Mediating
      Noninflammatory Proliferation and Dissemination of Commensal Enterococci.
AB  - Enterococci are Gram-positive commensals of the mammalian intestinal tract and
      harbor intrinsic resistance to broad-spectrum cephalosporins. Disruption of
      colonization resistance in humans by antibiotics allows enterococci to
      proliferate in the gut and cause disseminated infections. In this study, we used
      Enterococcus faecalis (EF)-colonized mice to study the dynamics of enterococci,
      commensal microbiota, and the host in response to systemic ceftriaxone
      administration. We found that the mouse model recapitulates intestinal
      proliferation and dissemination of enterococci seen in humans. Employing a
      ceftriaxone-sensitive strain of enterococci (E. faecalis JL308), we showed that
      increased intestinal abundance is critical for the systemic dissemination of
      enterococci. Investigation of the impact of ceftriaxone on the mucosal barrier
      defenses and integrity suggested that translocation of enterococci across the
      intestinal mucosa was not associated with intestinal pathology or increased
      permeability. Ceftriaxone-induced alteration of intestinal microbial composition
      was associated with transient increase in the abundance of multiple bacterial
      operational taxonomic units (OTUs) in addition to enterococci, for example,
      lactobacilli, which also disseminated to the extraintestinal organs.
      Collectively, these results emphasize that ceftriaxone-induced disruption of
      colonization resistance and alteration of mucosal homeostasis facilitate
      increased intestinal abundance of a limited number of commensals along with
      enterococci, allowing their translocation and systemic dissemination in a healthy
      host.

PMID- 30224554
TI  - Effect of CS preexposure on the conditioned ejaculatory preference of the male
      rat: behavioral analyses and neural correlates.
AB  - Early experiences with sexual reward play a pivotal role in the formation of
      sexual behavior and partner preference. Associations of salient partner cues, or
      even neutral cues on a partner, with sexual reward states are a product of
      Pavlovian learning. However, the extent to which first experiences that associate
      a neutral stimulus with no immediate consequence, and how that association may
      affect subsequent associability after being paired with a sexual reward state
      after copulation to ejaculation, remains unclear. To address this question,
      sexually naive males were preexposed over one or five trials to almond scented
      gauze pads prior to training during which half of the males were trained 10 times
      with scented receptive females, and the other half with unscented receptive
      females. A final test of partner preference was conducted in a large open field
      containing two sexually receptive females, one scented and the other unscented.
      Males developed a conditioned ejaculatory preference for the type of female they
      were trained with, except when they were preexposed five times to the odor and
      then trained with females bearing the same odor, indicating a significant CS
      preexposure effect. One CS preexposure was not sufficient to inhibit subsequent
      conditioning. Exposure to the scent before perfusion for inmunohistochemistry,
      revealed different patterns of brain activation in brain areas previously
      associated with the development of partner preference, like the medial preoptic
      area, ventral tegmental area, nucleus accumbens, basolateral amygdala, among
      others, depending on group membership. Thus, CS preexposure results in a
      subsequent impairment of the association that links the odor cue to sexual reward
      and preference. This highlights the impact of the first sexual experiences in
      future partner preference.

PMID- 30224555
TI  - First sexual experiences determine the development of conditioned ejaculatory
      preference in male rats.
AB  - We have shown previously that male rats develop a conditioned ejaculatory
      preference (CEP) for females scented with a neutral odor like almond or lemon
      that is paired with the male's post-ejaculatory reward state during their first
      and subsequent early sexual experiences. However, preexposing males to the
      neutral odor alone prior to its pairing with sexual reward results in latent
      inhibition. Here, we examined the phenomenon of unconditioned stimulus (US)
      preexposure, in which male rats were preexposed to the ejaculatory reward state
      either one or five times with scented (ScF) versus unscented (UnScF) females
      prior to multiple ejaculatory trials with females in the opposite condition
      (e.g., ScF preexposure received 10 subsequent ejaculatory trials with UnScF,
      whereas UnScF preexposure received 10 subsequent ejaculatory trials with ScF). As
      before, mate and partner preference was evaluated in an open field where each
      male had access to two females, one ScF and the other UnScF. Males that underwent
      five trials of preexposure did not display a CEP for either female. Conversely,
      males preexposed once to a ScF, and later trained with UnScF developed a
      preference for the latter, whereas males preexposed once to the UnScF, and then
      trained with ScF did not show a preference for any of the females. Subsequent
      exposure to the odor cue alone revealed different patterns of brain activation in
      areas related to sexual behavior that depended on the animal's group membership.
      Altogether, these findings demonstrate the pivotal role of first sexual
      experiences in the establishment of future sexual partner preference in the male
      rat, and suggest an innate preference for estrous odors over neutral odors that
      can become conditioned subsequently as predictors of sexual reward.

PMID- 30224556
TI  - Developmental changes in plasticity, synaptic, glia, and connectivity protein
      levels in rat medial prefrontal cortex.
AB  - The medial prefrontal cortex (mPFC) plays a critical role in complex brain
      functions including decision-making, integration of emotional, and cognitive
      aspects in memory processing and memory consolidation. Because relatively little
      is known about the molecular mechanisms underlying its development, we quantified
      rat mPFC basal expression levels of sets of plasticity, synaptic, glia, and
      connectivity proteins at different developmental ages. Specifically, we compared
      the mPFC of rats at postnatal day 17 (PN17), when they are still unable to
      express long-term contextual and spatial memories, to rat mPFC at PN24, when they
      have acquired the ability of long-term memory expression and finally to the mPFC
      of adult rats. We found that, with increased age, there are remarkable and
      significant decreases in markers of cell activation and significant increases in
      proteins that mark synaptogenesis and synapse maturation. Furthermore, we found
      significant changes in structural markers over the ages, suggesting that
      structural connectivity of the mPFC increases over time. Finally, the substantial
      biological difference in mPFC at different ages suggest caution in extrapolating
      conclusions from brain plasticity studies conducted at different developmental
      stages.

PMID- 30224558
TI  - Sign-tracking is an expectancy-mediated behavior that relies on prediction error
      mechanisms.
AB  - When discrete localizable stimuli are used during appetitive Pavlovian
      conditioning, "sign-tracking" and "goal-tracking" responses emerge. Sign-tracking
      is observed when conditioned responding is directed toward the CS, whereas goal
      tracking manifests as responding directed to the site of expected reward
      delivery. These behaviors seem to rely on distinct, though overlapping neural
      circuitries, and, possibly, distinct psychological processes as well, and are
      thought to be related to addiction vulnerability. One currently popular view is
      that sign-tracking reflects an incentive motivational process, whereas goal
      tracking reflects the influence of more top-down cognitive processes. To test
      these ideas, we used illness-induced outcome-devaluation and Kamin blocking
      procedures to determine whether these behaviors rely on similar or distinct
      underlying associative mechanisms. In Experiments 1 and 2 we showed that outcome
      devaluation reduced sign-tracking responses, demonstrating that sign-tracking is
      controlled by reward expectancies. We also observed that post-CS goal-tracking in
      these animals is also devaluation sensitive. To test whether these two types of
      behaviors rely on similar or different prediction error mechanisms, we next
      tested whether Kamin blocking effects could be observed across these two classes
      of behaviors. In Experiment 3 we asked if sign-tracking to a lever CS could block
      the development of goal-tracking to a tone CS; whereas in Experiment 4, we
      examined whether goal-tracking to a tone CS could block sign-tracking to a lever
      CS. In both experiments blocking effects were observed suggesting that both sign-
      and goal-tracking emerge via a common prediction error mechanism. Collectively,
      the studies reported here suggest that the psychological mechanisms mediating
      sign- and goal-tracking are more similar than is commonly acknowledged.

PMID- 30224559
TI  - Cochrane director's expulsion results in four board members resigning.

PMID- 30224557
TI  - Effects of corticosterone on mild auditory fear conditioning and extinction; role
      of sex and training paradigm.
AB  - Multiple lines of evidence suggest that glucocorticoid hormones enhance memory
      consolidation of fearful events. However, most of these studies involve male
      individuals. Since anxiety, fear, and fear-associated disorders present
      differently in male and female subjects we investigated in mice whether male and
      female mice perform differently in a mild, auditory fear conditioning task and
      tested the modulatory role of glucocorticoid hormones. Using an auditory fear
      conditioning paradigm with different footshock intensities (0.1, 0.2, and 0.4 mA)
      and frequencies (1* or 3*), we find that intraperitoneal injections with
      corticosterone (2 mg/kg) immediately after training, altered freezing behavior
      when repeated footshocks were applied, and that the direction of the effects were
      opposite in male and female mice. Effects were independent of footshock
      intensity. In male mice, corticosterone consistently increased freezing behavior
      in response to the tone, whereas in female mice, corticosterone reduced freezing
      behavior 24 h after training. These effects were not related to the phase of the
      oestrous cycle. In addition, corticosterone enhanced extinction learning for all
      tones, in both male and female mice. These results emphasize that glucocorticoid
      hormones influence memory consolidation and retrieval, and underscore sex
      specific effects of glucocorticoid hormones in modulating conditioned fear
      responses.

PMID- 30224560
TI  - From Spokane to McCall.

PMID- 30224561
TI  - Developments to monitor the exhalome in organ failure in critically ill patients
      a look into the future.
AB  - Critically ill patients typically need some kind of functional organ support or
      replacement. Cardiopulmonary and renal replacement therapies are well established
      measures in intensive care units. However, there are also inherent risks
      associated with these treatments. The appropriate and timely commencement,
      maintenance and termination of organ replacement procedures currently use weak
      surrogates as decision support in clinical practice. A more reasonable
      application of extracorporeal organ support can be expected to potentially lower
      adverse events and save costs in healthcare systems, if a precise online
      monitoring was available. The analysis of the exhalome offers great opportunities
      to detect circulatory, pulmonary, and renal failure in critically ill patients.
      Volatile organic compounds and exhalation patterns are associated with a series
      of metabolic disorders and may be key to indicate the appropriate time point for
      initiation, maintenance and termination of organ support technologies. It may
      thus be expected that mortality, infection risk, replacement therapy days, and
      medical costs of intensive care treatment may possibly be reduced using exhalome
      analysis for control of organ replacement therapies in the distant future.

PMID- 30224562
TI  - The effects of a single or double GnRH dose on pregnancy survival in high
      producing dairy cows carrying singletons or twins.
AB  - Pregnancy loss during the late embryonic and early fetal periods influences dairy
      herd economy. The objectives of this study were to (1) investigate the effects of
      a single or double GnRH dose administered at the time of pregnancy diagnosis (28
      34 days post-AI) on the pregnancy survival of cows in their third lactation or
      further carrying live singletons or unilateral twins, and (2) examine the impacts
      of GnRH treatment on subsequent twin reduction in twin pregnancies. Cows carrying
      singletons (n = 1,054) or unilateral twins (n = 379) were assigned at the time of
      pregnancy diagnosis to the following groups: control (no treatment), GnRH (100
      MUg GnRH), and 2GnRH (200 MUg GnRH). Pregnancy loss was recorded in 180 of the
      1,433 cows (12.6%) at 58-64 days post-AI. Based on the odds ratios, there was a
      significant (P < 0.0001) interaction between the treatment group and twin
      pregnancy. This interaction implies that control cows carrying twins were 3.2
      times more likely to suffer pregnancy loss than the other cows, whereas the GnRH
      and 2GnRH treatment groups cows carrying singletons or twins had pregnancy loss
      rates similar to the control cows carrying singletons. Twin reduction was
      observed in 35 twin pregnancies (9.2%). Cows in the GnRH and 2 GnRH groups were
      seven times more likely to show twin reduction than control cows. Our results
      indicate that GnRH administered at the time of pregnancy diagnosis had no
      beneficial effects in cows carrying singletons. In contrast, for twin
      pregnancies, the treatment increased the rate of pregnancy survival and was
      accompanied by an increase in the twin reduction rate.

PMID- 30224563
TI  - Evaluation of Photocatalytic Abilities by Variation of Conductivity and Dimethyl
      Sulfoxide: Photocatalytically Active TiO2-coated Wire Mesh Prepared via a Double
      layer Coating Method.

PMID- 30224564
TI  - A Liquid-core Liquid-cladding Optical Waveguide Based on Thermal Gradients across
      Laminar Flow of Water in Capillary Tubing.

PMID- 30224565
TI  - Screening of Extractant for the Determination of Active Sludge Trehalose in
      Sewage Treatment.

PMID- 30224566
TI  - A simultaneous detection of phosphoproteins and total proteins in SDS-PAGE using
      Calcon.

PMID- 30224567
TI  - Volume of Space within Cation-Exchange Resins Determined by Penetration of
      Inorganic Salt Solutions.

PMID- 30224568
TI  - An Ionic Liquid-based Microextraction Method for Ultra-High Preconcentration of
      Paraquat Traces in Water Samples Prior to HPLC Determination.

PMID- 30224569
TI  - Nanoparticle-based point of care immunoassays for in vitro biomedical
      diagnostics.

PMID- 30224570
TI  - Bioresorbable Vascular Scaffolds: Is the Light Fading at the End of the Tunnel?

PMID- 30224571
TI  - Trifecta vs. Magna for Aortic Valve Replacement - Differences in Clinical Outcome
      and Valve Hemodynamics.
AB  - BACKGROUND: The number of surgical aortic valve replacements using bioprosthetic
      valves is increasing, and newer bioprosthetic valves may offer clinical
      advantages in Japanese patients, who generally require smaller replacement valves
      than Western patients. In this study we retrospectively evaluated the Trifecta
      and Magna valves to compare clinical outcomes and hemodynamics in a group of
      Japanese patients. Methods and Results: Data were retrospectively collected for
      103 patients receiving a Trifecta valve and 356 patients receiving a Magna valve
      between June 2008 and 2017. Adverse events, outcomes, and valve hemodynamics were
      evaluated. There were no significant differences in early or late outcomes
      between the Trifecta and Magna groups. In the early postoperative period, mean
      (+/-SD) pressure gradient (9.0+/-3.1 vs. 13.8+/-4.8 mmHg; P<0.01) and effective
      orifice area (1.68+/-0.46 vs. 1.46+/-0.40 m2; P<0.01) were significantly better
      for Trifecta, but the differences decreased over time. In particular, the
      interaction between time and valve type (Trifecta or Magna) was significantly
      different for mean pressure gradient between the 2 groups (P<0.01). Left
      ventricular mass regressed substantially in both groups, with no significant
      difference between them. There were no significant differences for severe patient
      prosthesis mismatch. CONCLUSIONS: Postoperative outcomes were similar for both
      valves. An early hemodynamic advantage for the Trifecta valve lasted to
      approximately 1 year postoperatively but did not persist.

PMID- 30224572
TI  - Bioresorbable Vascular Scaffolds: Is the Light Fading at the End of the Tunnel? -
      Reply.

PMID- 30224573
TI  - Identification of novel haplotypes and interpretation of gene flow of
      mitochondrial DNA control region of Eurasian otter (Lutra lutra) for the
      effective conservation.
AB  - The number and distribution of Eurasian otters have declined during twentieth
      century due to human activity and water pollution. The global conservation status
      of Eurasian otter is presently 'Near Threatened (NT)' and strictly protected by
      being listed on the international legislation and conventions. A number of
      studies using the mitochondrial DNA (mtDNA) control region (CR) have been
      conducted in order to effectively apply conservation and reintroduction programs,
      especially in Europe. However, aside from Europe, there have been few studies
      concerning genetic diversity and phylogeny of Eurasian otters. Therefore, in this
      study, we sequenced partial mtDNA CR sequences (232 bp) from five South Korean
      Eurasian otters and analyzed 27 otters originating from parts of northeast Asia
      (South Korea, China, Japan and Russia (Sakhalin)), and Europe. Out of 232 bp
      partial mtDNA CR sequences, 13 polymorphic sites (5.6%) were identified and 4
      novel mtDNA CR haplotypes (Lut16-19) were discovered from 12 Eurasian otters
      originating from northeast Asian region. In this study, a comprehensive analysis
      of genetic diversity and population structure of Eurasian otter between Europe
      and northeast Asia continents were conducted. Of these, different past
      demographic histories in Pleistocene period might have largely impacted the
      genetic structure of each population differently. In addition, low degree of gene
      flow, isolation by distance (IBD) pattern from geographically wide distanced
      dataset and analysis of molecular variance (AMOVA) also represented distinct
      genetic characteristics of Eurasian otter between Europe and northeast Asia.

PMID- 30224574
TI  - Biotic and abiotic substrates for enhancing Acinetobacter baumannii biofilm
      formation: New approach using extracellular matrix and slanted coverslip
      technique.
AB  - Acinetobacter baumannii has been well recognized as a problematic human pathogen
      and several reports has shown the incidence of multidrug and pandrug-resistant A.
      baumannii strains in infirmary infections. A. baumannii grows only on an air
      liquid interface and does not form a contiguous biofilm. Extracellular matrices
      (ECM) and slanted glass coverslips are (SGC) used as biofilm substrates and
      biofilms have been investigated by SEM, confocal and crystal violet staining. ECM
      has shown enhanced biofilm formation under dynamic conditions rather than static
      conditions. SGC biofilm yield assay has shown higher levels of continuous layers
      and packed thicker biofilm formation with glass coverslip inserts, up to 1.7 to 3
      times higher biofilm formation, than when compared with no glass coverslip
      inserts. A media immersed ECM study revealed that biofilm grown on extracellular
      matrixes formed thread-like pili structures, and that these structures had
      contact with the ECM and also showed excellent cell-to-cell interaction. In
      summary, A. baumannii showed higher biofilm formation capacities with ECM, while
      the prominent results were directly related with the biofilm formation capacity
      of A. baumannii. For the initial step of biofilm formation, adherence is an
      important factor and, consequently, strains with a comparatively high capability
      to adhere to extracellular matrices and slanted glass coverslips provide a new
      method of enhanced biofilm growth for in vitro assays. ECM can be used as a
      substrate for immersed biofilm formation studies and the SGC method for air
      liquid interface exposed biofilm formation studies, and these substrates can
      provide better biofilm growth and easy handling for in vitro adherence and
      biofilm assays.

PMID- 30224575
TI  - Assessment of fish iridoviruses using a novel cell line GS-1, derived from the
      spleen of orange-spotted grouper Epinephelus coioides (Hamilton) and susceptible
      to ranavirus and megalocytivirus.
AB  - A new cell line (GS-1) was developed from the spleen tissue of the orange-spotted
      grouper, Epinephelus coioides applied for viral infection studies of fish
      ranavirus and megalocytivirus. The cells proficiently multiplied in Leibovitz's L
      15 medium supplemented with 10% fetal bovine serum at temperatures between 20
      degrees C and 32 degrees C. Morphologically, the cell line comprised fibroblast
      like cells, and this was confirmed by immunostaining with vimentin, fibronectin,
      and desmin antibodies. The optimal temperature for grouper iridovirus (GIV) and
      infectious spleen and kidney necrosis virus (ISKNV) proliferation in GS-1 cells
      was 25 degrees C, and the highest titer of GIV was 108.4 TCID50/ml, and the
      highest titer of ISKNV was 105.2 TCID50/ml. Electron micrographs showed that the
      mean diameter of GIV virions was 180-220 nm, which was larger than ISKNV virions
      (160-200 nm). Negatively stained GIV particles possessed an envelope structure
      that was assembled by the three-layered structure with an inner electron-dense
      core surrounded by a lighter coat (mean diameter, 27 +/- 3 nm). The highest GIV
      induced mortality of groupers occurred at 25 degrees C, whereas the highest ISKNV
      induced mortality occurred at 30 degrees C. In summary, GS-1 cell line is a
      valuable tool for isolating and investigating fish ranavirus and megalocytivirus
      in the same host system.

PMID- 30224576
TI  - Actinomyces denticolens as a causative agent of actinomycosis in animals.
AB  - The name "Actinomyces suis" was applied to each actinomycete isolate from swine
      actinomycosis by Grasser in 1962 and Franke in 1973. Nevertheless, this specific
      species was not included in the "Approved List of Bacterial Name" due to absence
      of the type cultures. Therefore, "Actinomyces suis" based on the description of
      Franke 1973 has been considered as "species incertae sedis". We isolated a number
      of Actinomyces strains from swine. The representative strains of them was
      designated as Chiba 101 that was closely similar to the description in
      "Actinomyces suis" reported by Franke in 1973. Interestingly, it was found that
      the biological characteristics of these strains were also very similar to those
      of Actinomyces denticolens. Furthermore, the average nucleotide identity (ANI)
      value between strain Chiba 101 and the type-strain of Actinomyces denticolens
      (=DSM 20671T) was found to be 99.95%. Sequences of the housekeeping genes and 16S
      rRNA gene showed 100% homology. These results strongly suggested that
      "Actinomyces suis" Franke 1973 is the same species as Actinomyces denticolens.
      Since actinomycosis caused by Actinomyces denticolens have been demonstrated in
      horses recently, it is necessary to recognize that Actinomyces denticolens is the
      pathogenic actinomycetes in broader range of animals.

PMID- 30224578
TI  - Historical Changes in Histological Diagnosis of Lung Cancer.
AB  - BACKGROUND: Histological classification of lung cancer is essential for
      investigations of carcinogenesis and treatment selection. We examined the
      temporal changes of lung cancer histological subtypes. METHODS: Lung cancer cases
      diagnosed in the Life Span Study cohort between 1958 and 1999 were collected from
      tumor registries (TR), mainly consisting of population-based cancer registries. A
      total of 1,025 cases were histologically reviewed according to the World Health
      Organization 2004 Classification by a panel of pathologists (PP). Sensitivity and
      specificity of diagnoses in TR were calculated, assuming that the diagnosis by PP
      was the gold standard. RESULTS: Sensitivity and specificity were 0.91 and 0.92
      for adenocarcinoma (AD), respectively, and 0.92 and 0.94, respectively, for
      squamous cell carcinoma (SQ). They were similar for AD and SQ throughout the
      observation period. For small cell carcinoma (SM), sensitivity was low until
      about 1980 (0.47 in 1958-1969, and 0.61 in 1970-1979) and then became higher
      thereafter (0.98 in 1980-1989, and 0.95 in 1990-1999), whereas specificity was
      high during the whole period (range 0.99 to 1.00). Among 45 cases that were not
      reported as SM in TR but diagnosed as SM by PP, 16 cases were recorded as
      undifferentiated carcinoma in TR. CONCLUSION: Diagnosis of AD and SQ of lung
      cancer were generally consistent between TR records and PP review, but SMs tended
      to be coded as other histological types until the 1970s.

PMID- 30224577
TI  - Pathogenesis of the attenuated foot-and-mouth disease virus O/JPN/2000 in
      experimentally infected pigs.
AB  - We examined the pathogenesis of the attenuated foot-and-mouth disease virus
      (FMDV) O/JPN/2000 in pigs. The virus used in this study was passaged three times
      in primary bovine kidney (BK) cells and once in baby hamster kidney-21 (BHK-21)
      cells after isolation. A plaque assay demonstrated that this virus exhibited the
      small plaque (SP) phenotype. There was no clinical or histological evidence of
      vesicular lesions in pigs intraorally inoculated with 106 50% tissue culture
      infectious dose (TCID50)/ml of the SP virus (SPV) of FMDV O/JPN/2000. Although
      fever was detected from 2 or 3 days post inoculation (dpi), there was no other
      prominent clinical sign up to 6 dpi. Virus shedding from saliva and nasal swab
      samples was not observed in any pigs inoculated with the SPV of FMDV O/JPN/2000.
      In the foot, mild lamellar degeneration of prickle cells in the upper layer of
      the stratum spinosum was histologically observed without development into
      vesicular or necrotic lesions. Immunohistochemical virus antigen- and terminal
      deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL)-positive
      reactions observed in the foot at 1 dpi seemed to disappear after 3 and 6 dpi.
      Our findings suggest that the SPV of FMDV O/JPN/2000 had low pathogenicity
      against pigs by intraoral inoculation.

PMID- 30224579
TI  - Psychiatric Admissions and Length of Stay During Fiscal Years 2014 and 2015 in
      Japan: A Retrospective Cohort Study Using a Nationwide Claims Database.
AB  - BACKGROUND: A better understanding of resource use of new psychiatric admissions
      is important for healthcare providers and policymakers to improve psychiatric
      care. This study aims to describe the pattern of new psychiatric admissions and
      length of stay in Japan. METHODS: A retrospective cohort study was conducted
      using data from the National Database of Health Insurance Claims and Specific
      Health Checkups of Japan (NDB). All patients newly admitted to psychiatric wards
      from April 2014 through March 2016 were included and followed up until discharge
      to the community. RESULTS: Our sample included 605,982 admissions from 1,621
      hospitals over 2 years. The average monthly number of admissions was 25,024 in
      fiscal year 2014 and 25,475 in fiscal year 2015. There was a seasonal trend in
      the number of admissions, with a peak in summer (in July). The discharge rates
      within 90 days and 360 days were 64.1% and 85.7%, respectively, and varied by
      type of hospital fee and by hospital. For example, the range of hospital-level
      discharge rate within 90 days in psychiatric emergency units was 46.0-75.3% in
      the 1st (lowest) quintile, while it was 83.6-96.0% in the 5th (highest) quintile.
      The prefecture-level indicators in the NDB and the 630 survey had correlations of
      >0.70. CONCLUSIONS: Our study provides fundamental information on resource use of
      new psychiatric admissions in Japan. Although using the NDB has substantial
      benefits in monitoring resource use, the results should be interpreted with some
      caution owing to methodological issues inherent in the database.

PMID- 30224580
TI  - The relative association of collective efficacy in school and neighborhood
      contexts with adolescent alcohol use.
AB  - BACKGROUND: It is unclear that either neighborhood collective efficacy or school
      collective efficacy can be associated with adolescent alcohol use. This study
      aimed to examine the relative contributions of collective efficacy both in school
      and in the neighborhood contexts to alcohol use among Japanese adolescents.
      METHODS: A cross-sectional study was conducted in public high schools across
      Okinawa and Ibaraki Prefectures in Japan in 2016. The study participants
      consisted of 3,291 students in grades 10 through 12 cross-nested in 51 schools
      and 107 neighborhoods. Alcohol use was measured by current alcohol drinking, that
      is self-reported drinking on at least one day in the past 30 days. Collective
      efficacy was measured by scales of social cohesion and informal social control in
      school and the neighborhood. Contextual-level collective efficacy was measured by
      aggregated school-level and neighborhood-level individual responses,
      respectively. We used non-hierarchical multilevel models to fit the cross-nested
      data. RESULTS: Significant variation in alcohol use was shown between schools,
      but not between neighborhoods. After adjusting for covariates, school collective
      efficacy at individual- and contextual-levels were protectively associated with
      alcohol drinking (Odds Ratio [OR] for the increase of one standard deviation from
      the mean 0.72, 95% Confidence Interval [CI], 0.63-0.82; OR 0.61, 95% CI, 0.49
      0.75), whereas neighborhood collective efficacy at individual- and contextual
      levels were not associated with alcohol consumption. CONCLUSION: The school-level
      associations with adolescent alcohol use may have the greater impact than the
      neighborhood-level associations. Adolescent drinking prevention efforts should
      include enhancing school collective efficacy.

PMID- 30224581
TI  - Long-term Trends in Prevalence of Neural Tube Defects in Japan.

PMID- 30224582
TI  - Spontaneous virilization around puberty in NR5A1-related 46,XY sex reversal:
      additional case and a literature review.
AB  - A heterozygous NR5A1 mutation is one of the most frequent causes of 46,XY DSD
      (disorders of sex development). We here reported a NR5A1-related 46,XY DSD
      patient, who first received endocrinological attention at 10 years of age for
      clitoromegaly. The patient had been reared as a girl, and no signs of
      virilization had been detected before. On examination, her clitoris was 35 mm
      long and 10 mm wide, with Tanner 3 degrees  pubic hair. Urogenital sinus and
      labial fusion was absent, while her uterus was found to be severely hypoplastic.
      Her basal testosterone level was 94.8 ng/dL, suggesting the presence of
      functioning Leydig cells. Gonadal histology revealed bilateral dysplastic testes
      consisting of mostly Sertoli cell-only tubules and Leydig cell hyperplasia. Novel
      heterozygous Arg313Leu substitution in NR5A1 was identified in the patient.
      Literature search confirmed twelve other cases of this scenario, namely, severe
      under-virilization in utero followed by spontaneous virilization around puberty
      in NR5A1-related 46,XY DSD. Of interest, Leydig cell hyperplasia was documented
      in 6 out of 9 patients for whom testicular histology was available. To keep in
      mind about the possible restoration of Leydig cell function around puberty, even
      in patients without discernible in utero androgen effect, may be of clinical
      significance, because it will give a great impact on the judgement about sex
      assignment.

PMID- 30224583
TI  - The development of a public health nurses precepting experiential learning scale.
AB  - Objectives The Japanese government has supported public health nurses' systematic
      career development and preceptors' learning. Previous studies on precepting
      public health nurses indicated the value of precepting for career development.
      However, assessment scales for preceptor learning were not found. The purpose of
      this study was to develop the "PHN Precepting Experiential Learning Scale" (PHN
      PELS) based on Kolb's experiential learning theory.Methods This study included
      three phases of questionnaire development. First, the preliminary qualitative
      pilot study resulted in the PHN-PELS. The second pilot study was a questionnaire
      survey, returned by 52 (54.2%) public health nurses (PHNs) who had examined the
      validity and modified the items. Finally, a nation-wide questionnaire survey was
      conducted for PHNs who precepted novice PHNs in public health units from 2012 to
      2016.Results Of the 868 questionnaires mailed to 86 public health units, 438
      (59.4%) were returned with 378 (43.5%) valid responses. PHN-PELS has 20 items
      forming four sub-scales, with confirmed content validity, construct validity, and
      reliability (alpha>.7). Sub-scales were: "Role Performance of Fostering Novice
      PHN," "Self-development as a PHN," "Sharing to Foster Novice PHN," and "Improving
      Career Development Environment."Conclusion Scale development of the PHN-PELS
      resulted in four sub-scales with 20 items; its validity and reliability were
      supported. The PHN-PELS measures experiential learning in precepting novice PHNs,
      therefore, its usability is recommended for preceptors to evaluate their
      experiential learning and for preceptor training program in selecting sub-scales
      as appropriate.

PMID- 30224584
TI  - [Effects of Brief Cognitive Behavioral Therapy for insomnia on sleep and usage of
      hypnotics among community-dwelling older adults: Randomized controlled trial].
AB  - Objectives Chronic insomnia is common in late adulthood. A non-pharmacological
      approach should take priority in the treatment of insomnia for the elderly. Many
      studies have shown the efficacy of Cognitive Behavioral Therapy for Insomnia (CBT
      I) for elderly diagnosed with insomnia. However the effect of CBT-I on mild
      insomnia among older adults in community settings has not been ascertained. We
      conducted a randomized controlled trial to evaluate the effectiveness of a brief
      CBT-I delivered by nurses, which is feasible in community settings, to improve
      sleep quality and decrease the dose of hypnotics use for older adults.Methods
      Participants aged 60 years and over were enrolled in this study. The participants
      in the intervention group were administrated the brief CBT-I consisting of a
      group session (60 min) and an individual session (30 min). The primary outcomes
      were the score differences in the Pittsburgh Sleep Quality Index (PSQI) and
      Insomnia Severity Index (ISI). The secondary outcomes were the change in the
      proportion of people diagnosed with insomnia and the dose of hypnotics used. The
      follow-up period was 3 months.Results The score on PSQI in the intervention group
      (n=41) significantly decreased compared to the control group (n=38). The effect
      size (Cohen's d) was 0.56 (95% Confidence interval [CI], 0.07 to 1.05). The score
      on ISI also decreased significantly and Cohen's d was 0.77 (95%CI, 0.27 to 1.26).
      According to subgroup analysis, Number Needed to Treat (NNT) for improvement of
      insomnia was 2.8 (95%CI, 1.5-17.2) and NNT for decreasing of dose of hypnotics
      use was 2.8 (95%CI, 1.5-45.1).Conclusion The present results have demonstrated
      that the brief CBT-I significantly improved subjective evaluation of sleep
      quality and insomnia symptoms among the elderly. In addition, the brief CBT-I
      decreased the usage of hypnotics. Further studies are needed in terms of the
      procedure and the effects of brief CBT-I for older adults living in a community.

PMID- 30224585
TI  - [Establishment of disaster health management programs by public health centers in
      Japan with the introduction of the Disaster Health Emergency Assistance Team].

PMID- 30224586
TI  - [Factors related to eating behaviors in early childhood: Relationships between
      autistic tendency, sensory characteristics, and childcare environment].
AB  - Objective The objective of this study was to examine the influence of
      environmental factors on eating behaviors of children.Method The participants
      were the caregivers of 1,678 children attending nursery schools or kindergartens
      in two different cities of a prefecture. We distributed several self-administered
      questionnaires to the caregivers in conjunction with collaborating organizations.
      The participants returned the questionnaires either to collection boxes placed at
      the collaborating organizations facilities or by mailing them. The questionnaires
      included assessment of the child's basic attributes, caregiver assessments of
      eating behaviors, the Social Responsiveness Scale (SRS) measure of autistic
      traits, the Japanese Sensory Inventory-Revised (JSI-R), and the Index of Child
      Care Environment (ICCE). We conducted a chi-square (chi2) test, Fisher's exact
      test, and a multiple regression analysis.Results We received responses from 843
      participants (response rate=50.4%), and of those, 583 were considered valid
      (34.7%). The mean number of problematic eating behaviors for each child as
      perceived by the caregivers was 2.43+/-2.26. In general, caregivers thought that
      about 40% of the children had an unbalanced diet and about 30% had a problem of
      "not being able to sit still." The multiple regression analysis showed that the
      number of problematic eating behaviors was significantly and positively affected
      by the SRS T-score total (beta=0.188, P<0.001), sense of taste (beta=0.319,
      P<0.001) and auditory sense (beta=0.168, P<0.001) in JSI-R. A positive
      relationship was found between the environmental factors of human stimulation
      (beta=0.096, P=0.010) and social support (beta=0.085, P=0.022). A negative
      relationship was found between sense of smell (beta=-0.108, P=0.013), number of
      siblings (beta=-0.100, P=0.005), age (beta=-0.077, P=0.029), and sex (beta=
      0.091, P=0.010).Conclusion Our study results showed that having an unbalanced
      diet and "not being able to sit still" were typical features of eating behaviors.
      The number of problematic eating behaviors was associated with personal factors
      such as autistic tendency and sensory characteristics, and also with
      environmental factors, such as human stimulation and social support. Our findings
      show the importance of evaluating all relevant factors when dietary guidance is
      provided in the treatment of problematic eating behaviors.

PMID- 30224587
TI  - Myocardial Rupture Due to Metastasis of Urothelial Carcinoma.

PMID- 30224588
TI  - Angiographic Appearance of Patent Saphenous Vein Graft 32 Years After Coronary
      Artery Bypass Grafting.

PMID- 30224589
TI  - Peripheral Signs of Infective Endocarditis.

PMID- 30224590
TI  - Concomitance of Polymorphisms in Glutathione Transferase Omega Genes Is
      Associated with Risk of Clear Cell Renal Cell Carcinoma.
AB  - Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes, play
      an important role in the onset and progression of renal cell carcinoma (RCC).
      However, novel GST omega class (GSTO), consisting of GSTO1-1 and GSTO2-2
      isoenzymes, has not been studied in RCC yet. Two coding single nucleotide
      polymorphisms (SNPs) supposedly affect their functions: GSTO1*C419A (rs4925)
      causing alanine to aspartate substitution (*A140D) and GSTO2*A424G (rs156697)
      causing asparagine to aspartate substitution (*N142D), and have been associated
      with several neurodegenerative diseases and cancers. Functional relevance of yet
      another GSTO2 polymorphism, identified at the 5' untranslated (5'UTR) gene region
      (GSTO2*A183G, rs2297235), has not been clearly discerned so far. Therefore, we
      aimed to assess the effect of specific GSTO1 and GSTO2 gene variants,
      independently and in interaction with established risk factors (smoking, obesity
      and hypertension) on the risk for the most aggressive RCC subtype, the clear cell
      RCC (ccRCC). Genotyping was performed in 239 ccRCC patients and 350 matched
      controls, while plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a
      biomarker of oxidative DNA damage, were determined by ELISA. As a result,
      combined effect of all three variant genotypes exhibited almost 3-fold risk of
      RCC development. Additionally, this association was confirmed at the haplotype
      level [variant GSTO1*A/GSTO2*G (rs156697)/GSTO2*G (rs2297235) haplotype],
      suggesting a potential role of those variants in propensity to RCC. Regarding the
      gene-environment interactions, variant GSTO2*G (rs156697) homozygous smokers are
      at higher ccRCC risk. Association in terms of oxidative DNA damage was found for
      GSTO2 polymorphism in 5'UTR and 8-OHdG. In conclusion, the concomitance of GSTO
      polymorphisms may influence ccRCC risk.

PMID- 30224591
TI  - Green synthesis and inhibitory effects against oral pathogens of silver
      nanoparticles mediated by rice extracts.
AB  - Rice is staple food for people in many countries for centuries. It is therefore
      considered as safe and environmental friendly material for pharmaceutical
      formulations. In the present study, aqueous extracts of three different parts of
      rice grain; rice bran (RB), rice husk (RH), and rice germ (RG) were compared for
      their use as reducing agents in synthesis of silver nanoparticles (AgNPs). AgNPs
      from those three different parts of rice, RB-AgNPs, RH-AgNPs, and RG-AgNPs,
      respectively showed different reducing activity, which the highest capacity was
      RB. RG-AgNPs and RB-AgNPs showed the maximum absorption of AgNPs at 440 nm
      whereas that of RH-AgNPs was at 480 nm. FTIR spectra of all AgNPs indicated the
      presence of different functional groups from rice attached to the nanoparticles
      and these groups prevented the particle agglomeration. Size analysis using
      dynamic light scattering revealed that RB-AgNPs was the smallest particles (346.4
      +/- 36.8 nm) and possessed the highest negative zeta potential. Antimicrobial
      test showed that the AgNPs obtained from green synthesis mediated by rice
      extracts have great antimicrobial activity against Streptococcus mutans, the
      severe oral pathogenic bacteria causing dental caries. These results suggest that
      aqueous extracts of RB, RH, and RG have potential to be used as reducing agents
      in synthesis of silver nanoparticles.

PMID- 30224592
TI  - Caesalpinia sappan: A promising natural source of antimicrobial agent for
      inhibition of cariogenic bacteria.
AB  - From the previous findings, the ethanolic fractionated extract of Caesalpinia
      sappan (F-EtOH) has high activity against Streptococcus mutans, the most severe
      cariogenic bacteria. The present study was aimed to isolate and identify the
      active compound of F-EtOH and compare its inhibitory activity against the biofilm
      of S. mutans as well as the cytotoxicity to oral fibroblast cells with F-EtOH.
      Compound isolation was done by column chromatography. The active compound was
      identified using liquid chromatography-mass spectrometry with electrospray
      ionization and nuclear magnetic resonance spectroscopy. It was found that the
      major compound of F-EtOH is brazilin. F-EtOH and brazilin were compared for
      inhibitory potential on the biofilms of three strains of S. mutans. The results
      exhibited that both F-EtOH and brazilin had potential on inhibiting biofilm
      formation and eradicating the preformed biofilms and their activity was dose
      dependent. F-EtOH showed significantly less toxic to normal periodontal ligament
      fibroblast than brazilin. At low concentration of 1- and 2-MBC, F-EtOH showed
      higher effective than brazilin. The results of our study suggest that the
      antibacterial activity of F-EtOH is according to the synergistic effects of the
      existing compounds including brazilin in F-EtOH.

PMID- 30224593
TI  - Effect of rice variety and modification on antioxidant and anti-inflammatory
      activities.
AB  - The effects of variety and modification of rice on its antioxidant and anti
      inflammatory activities were investigated. White rice varieties; Jasmine (JM) and
      Saohai (SH), and pigmented rice varieties; Doisket (DS) and Homnil (HN) were
      used. The modified rice samples were obtained from chemical modification using
      etherification reaction. The activities of the modified rice samples were
      compared with the ethanol extracts of the raw rice at the same rice
      concentration. Antioxidant activity was measured by the free radical scavenging
      activity tests and ferric reducing power assay. Results indicated that the
      ethanol extracts of raw rice had higher antioxidant activity than the modified
      rice. Among the raw rice tested, the pigmented rice showed higher antioxidant
      activity than white rice. Trolox equivalent antioxidant capacity values from free
      radical scavenging activity test were revealed that 50% ethanol extracts of HN
      and DS possessed the highest antioxidant activity. Ferric reducing power assay
      showed that 50% ethanol extracts of DS had the highest antioxidant activity. The
      anti-inflammatory activity was evaluated in vitro using a lipopolysaccharide
      stimulated RAW264.7 macrophage cell model with enzyme-linked immunosorbent assay.
      Absolute ethanol extracts of HN reduced interleukin-6 secretion whereas that of
      DS suppressed interleukin-6 and tumor necrosis factor -alpha secretion. These
      results indicate that variety of rice, chemical modification, and extracting
      solvent were the factors that play an important role on antioxidant and anti
      inflammatory activity. This study supports the potential use of the pigmented
      rice, especially DS, as a promising choice of a natural source because of its
      antioxidant and anti-inflammatory activities.

PMID- 30224594
TI  - Fungal-derived xenobiotic exhibits antibacterial and antibiofilm activity against
      Staphylococcus aureus.
AB  - Staphylococcus aureus is an opportunistic pathogen, responsible for superficial
      and invasive infections both in nosocomial and community-acquired settings. The
      incidences of infection have become more problematic attributable to emerging
      drug resistance and biofilm formation. These challenges suggest the need for new
      antimicrobial agents against S. aureus. In present work, we purified a fungal
      xenobiotic (FI3) which elicits a potent antimicrobial activity against a list of
      tested microbes including methicillin sensitive (MSSA) and methicillin resistance
      (MRSA) S. aureus. The cell growth of MSSA and MRSA were completely ceased with
      the 1* minimum inhibitory concentration (MIC); 32 ug/mL and 128 ug/mL,
      respectively. The cell viability severely decreased within 90 min, due to
      disturbance of membrane homeostasis. This bactericidal effect was enhanced at
      lower pH (pH 4) with a speculation to retain positive charge. The FI3 potently
      disrupts biofilm adherence at 64 ug/mL and found to be a safe with no toxic
      effect on mammalian tissue. FI3 also leads to increase the potency of tested
      antibiotics. Taken together, we established that FI3 has a potent antimicrobial
      activity against tested microbes and safer to human tissue. It may be proven a
      leading molecule for the treatment of bacterial infections.

PMID- 30224595
TI  - Constipation in the elderly in a Japanese long-term medical facility: An
      ultrasonographic investigation.
AB  - This study aims to assess the fecal retention in elderly patients using colonic
      ultrasonography (US) in Japanese long-term care facility and determine the
      correlation between nutrition management methods and the fecal retention by US.
      This cross-sectional, single-center study was conducted in a long-term care
      facility in Japan. Patients with chronic constipation fulfilled the Rome III
      criteria for the diagnosis of functional constipation. US was performed on
      constipation patients with 4-day fecal retention before starting the standard
      management of constipation. After patients had defecated, nurses checked the
      outside of feces using King's Stool Chart and Bristol Stool Chart. All of 32
      patients underwent the management of suppository laxative, the daily life
      independence level in grade C. In all cases, the King's Stool Chart did not
      detect > 200 g of fecal matter; the Bristol Stool Chart revealed type 5-7 in
      56.2% of patients. The total parenteral nutrition and tube feeding did not
      completely detect type 1-2 in 0%. While the fecal retention groups comprised
      15.6%, the non-fecal retention groups comprised 84.4%. The total parenteral
      nutrition did not completely detect the fecal retention in 0%. In the non-fecal
      retention groups, the King's Stool Chart indicated < 100 g in 81.8%, and the
      Bristol Stool Chart indicated type 5-7 in 100%. In conclusion, fecal properties
      of elderly constipation patients with the long-term parenteral nutrition should
      be assessed in follow-up examination by US, which is possible for personalized
      medical care by US, to avoid the administered regular management of constipation.

PMID- 30224596
TI  - Whole body vibration exercise in the management of cancer therapy-related
      morbidities: A systematic review.
AB  - The purpose of this systematic review was to investigate the effects of whole
      body vibration (WBV) exercise in the management of cancer therapy-related
      morbidities. The PubMED and PEDro databases were used to access publications
      published in English about the use of whole body vibration (WBV) exercises in
      cancer patients until February 22nd 2017. The studies included were classified
      according to the level of evidence (LE) by the National Health and Medical
      Research Council Hierarchy of evidence and the methodological quality (MQ) by the
      PEDro scale. The four included studies (2 of them with "high" LE-II and MQ) were
      performed in patients with different types of cancer (i.e. breast, lung,
      prostate, solid or hematological), treated with WBV exercise to counteract the
      cancer therapy-related morbidities. The variables evaluated were muscle activity,
      subjective rate of perceived exertion, exercise capacity, muscle strength,
      quality of life, resting urinary incontinence and severity of peripheral
      neuropathy. Although WBV exercise appears to be a potential treatment procedure
      of cancer therapy-related morbidities, further additional studies are required to
      determine specific and tailored protocols to be used in the different stages of
      the disease.

PMID- 30224597
TI  - Criteria for the selection of switch OTC drugs based on patient benefits,
      efficacy, and safety [II]: Comparing the physicochemical and pharmaceutical
      properties of brand-name and switch OTC terbinafine hydrochloride cream.
AB  - The physicochemical properties (pH, yield value, and squeeze force) of a drug for
      dermatomycosis, a terbinafine hydrochloride-containing cream (a brand-name
      product), and 12 over-the-counter drugs (OTCs) were measured and compared to
      ascertain the characteristics of each product. The pH of the brand-name product,
      Lamisil, was 4.1, and that of the OTC products ranged from 4.2 to 7.6; Lamisil
      Plus (7.6) had a significantly higher pH. Moreover, the yield value for Lamisil,
      as an index of cream ductility, was 128 dyn/cm2, and that for the OTC products
      ranged from 110 to 887 dyn/cm2. In particular, the OTC products Damalin (887
      dyn/cm2), Barriact (512 dyn/cm2), and Exiv Deep (663 dyn/cm2) had a significantly
      higher yield value. In addition, the squeeze force was measured by attaching a
      HapLog(r) to the thumb and second finger. The squeeze force for Lamisil was 12.9
      N, and that for the OTC products ranged from 1.8 to 14.6 N. The OTC product
      Bilumon (1.8 N) had a significantly lower squeeze force. These results indicated
      that there were marked differences in the pharmaceutical properties of brand-name
      and OTC products. External preparations are characterized by their feel during
      use. Based on the current results, the pharmaceutical characteristics of drugs
      resulted in differences in their feel during use, suggesting that products
      appropriate for individual patients can be recommended.

PMID- 30224599
TI  - Erratum for "Anesthetic activity of plant essential oils on Cyprinus carpio (koi
      carp)" (Drug Discoveries & Therapeutics. 2018; 12(1):21-30.).
AB  - It has come to the authors' attention that their article entitled "Anesthetic
      activity of plant essential oils on Cyprinus carpio (koi carp)" (Drug Discoveries
      & Therapeutics. 2018; 12(1):21-30.) included an error in Table 2. The corrected
      Table 2 is printed below.

PMID- 30224598
TI  - Atypical cases of filariasis from a non-endemic area.
AB  - Filariasis can present in many different ways and pose significant dilemma to the
      clinician. We report four atypical cases of filariasis which presented as
      abdominal mass, cervical lymph node enlargement, fever in pregnancy and
      nosocomial febrile illness respectively. All the four cases were treated
      successfully with oral antifilarial agents. It is essential to be aware of such
      atypical presentations of filariasis so that prompt therapy can be initiated.

PMID- 30224600
TI  - The application of cellulose acetate replication sheets in enamel wear
      investigations.
AB  - Surface replication is a nondestructive evaluation technique applied in examining
      surfaces' cracks/wear. This is quite valuable when the surface of interest cannot
      be further manipulated by cutting or polishing to fit directly under a
      microscope. Replication by acetate sheets is one of the techniques applied in
      industrial, metallographic and anthropological wear/examination. Enamel is the
      outermost protective layer of human teeth and is subjected to mechanical stresses
      due to the masticatory function; thus, wear is inevitable in human teeth. This
      relatively inert hard tissue has been reported to possess some properties of both
      metals and glasses due to its unique delicate microstructure. This study
      investigated the applicability of replication sheets in registering wear induced
      features on human enamel surfaces. The sheets replicated wear features
      successfully with compatibility to use with multiple microscopes. Acetate sheets
      have a potential in enamel wear replication.

PMID- 30224601
TI  - Effects of silicate-based composite material on the proliferation and
      mineralization behaviors of human dental pulp cells: An in vitro assessment.
AB  - The objective of this study was to investigate the effects of a silicate-based
      composite material on proliferation and mineralization of human dental pulp cells
      (hDPCs), which was compared with those of calcium hydroxide (Ca(OH)2, CH) and
      tricalcium silicate (Ca3SiO5, C3S). HDPCs were cultured with CH, C3S and
      tricalcium silicate/dicalcium silicate (Ca3SiO5/Ca2SiO4, C3S/C2S) composites
      extract. The CCK-8 assay showed that the composite material stimulated the
      proliferation of hDPCs. The odontogenic marker genes and DSPP protein expression
      were more significantly up-regulated by the C3S/C2S composite material compared
      with pure CH and C3S. HDPCs cultured with composite material extract exert
      stronger ALP activity and alizarin red S staining. C3S/C2S composite material was
      advantageous over pure C3S by showing enhanced ability to stimulate the
      proliferation and odontogenic differentiation of hDPCs, suggesting that the
      C3S/C2S composite materials possess desirable biocompatibility and bioactivity,
      and might be a new type of pulp-capping agent and dentin alternative materials.

PMID- 30224602
TI  - Three-dimensional finite element analysis of the stability of mini-implants close
      to the roots of adjacent teeth upon application of bite force.
AB  - To investigate the cause of mandibular implant loss, we evaluated the stress
      distribution in the bone under bite force when the miniimplant was near the root
      using three-dimensional finite element analysis. Our analysis involved four
      finite element models with different distances between the implant and adjacent
      tooth root and three loading conditions. With loading of the tooth only or both
      the tooth and implant, the peak stress within the bone around the implant neck,
      displacement, and stress surrounding the bone near the root increased as the
      distance between the implant and root decreased. However, with separate loading
      of the implant, the stress did not correlate with the distance between the
      implant and root. Application of bite force increases stress within bones
      surrounding mini-implants near the roots of adjacent teeth and may threaten
      implant stability, but simple orthodontic loading has little effect on the stress
      distribution at the mini-implant-bone interface.

PMID- 30224603
TI  - Effects of silver diammine fluoride on bond strength of adhesives to sound
      dentin.
AB  - This study evaluated bonding of adhesives to dentin treated with silver diammine
      fluoride (SDF). Micro-shear bond strength (MSBS) to sound human dentin was
      investigated for 3 adhesive systems: Clearfil SE bond 2 (CSE), and Scotchbond
      Universal in self-etching (SBU) and phosphoric acid-etching (SBT) modes,
      following 4 different SDF application protocols (n=10); Control: treated with
      deionized water. P1: SDF applied for 10-s, no rinse. P2: SDF applied for 10-s,
      rinsed off after 1-min. P3: superficial dentin polished off after 24-h following
      P1. MSBS data were obtained after 24-h water storage at 37 degrees C. SDF
      significantly affected MSBS to dentin depending on the SDF protocol and adhesive
      system. Rinsing SDF off improved bond strength but superficial refreshing of
      SDFtreated dentin prior to bonding showed the highest bond strength. The two-step
      self-etch adhesive (CSE) and the universal adhesive in acid-etching mode (SBT)
      showed better performance than universal adhesive (SBU) alone on SDF treated
      dentin.

PMID- 30224604
TI  - Five-axis laser milling system that realizes more accurate zirconia CAD/CAM
      crowns by direct milling from fully sintered blocks.
AB  - Directly milling zirconia computer-aided design (CAD)/computer-aided
      manufacturing (CAM) crowns from fully sintered zirconia blocks using a five-axis
      laser milling system, compared with three-axis milling and full sintering by
      heating milled semi-sintered crowns, was investigated. The mechanical
      characteristics of zirconia specimens were similar across groups. The order of
      the marginal gap was three-axis>conventional (lingual thickness of 1.5 mm>0.5
      mm)>five-axis group (close to zero). The marginal shape was almost perfectly
      circular in all groups. The internal corner shape and gap were almost perfect for
      the five-axis milled crown but not for conventional and three-axis crowns. The
      roundness of the marginal and internal shapes was almost perfect in the five-axis
      milling group but not for the three-axis and conventional groups. These small
      distortions result in large marginal gaps. Results of the present study suggest
      the superiority of the five-axis milling system in creating a zirconia
      prosthesis.

PMID- 30224605
TI  - Spontaneous Isolated Superior Mesenteric Artery Dissection Requiring Emergent
      Surgery.
AB  - A 52-year-old man with a history of hypertension was referred to our hospital due
      to persistent abdominal pain. Abdominal palpation revealed remarkable rigidity
      and rebound tenderness all over the abdomen. Enhanced computed tomography
      demonstrated the superior mesenteric artery (SMA) dissection with a complete
      obstruction at the middle part of the SMA. Intraoperative findings showed
      significant necrosis in the most small intestine and surgical resection was
      performed. Emergent operation is warranted once abdominal pain becomes
      uncontrollable or intestinal necrosis is suspected. Physicians should pay careful
      attention to patients' symptoms and repeatedly perfume physical examinations.

PMID- 30224606
TI  - Lipoprotein Sub-Fractions by Ion-Mobility Analysis and Its Association with
      Subclinical Coronary Atherosclerosis in High-Risk Individuals.
AB  - AIMS: There is limited knowledge about the association of lipoprotein particles
      and markers of coronary atherosclerosis such as coronary artery calcification
      (CAC) in relatively young high-risk persons. This study examines the association
      of lipoprotein subfractions and CAC in high cardiometabolic risk individuals.
      METHODS: The study presents analysis from baseline data of a randomized trial
      targeted at high-risk workers. Employees of Baptist Health South Florida with
      metabolic syndrome or diabetes were recruited. At baseline, all 182 participants
      had lipoprotein subfraction analysis using the ion mobility technique and
      participants above 35 years (N=170) had CAC test done. Principal components (PC)
      were computed for the combination of lipoprotein subclasses. Multiple
      bootstrapped regression analyses (BSA) were conducted to assess the relationship
      between lipoprotein subfractions and CAC. RESULTS: The study population (N=170)
      was largely female (84%) with a mean age of 58 years. Three PCs accounted for 88%
      variation in the sample. PC2, with main contributions from VLDL particles in the
      positive direction and large LDL particles in the negative direction was
      associated with a 22% increase in CAC odds (P value <0.05 in 100% of BSA). PC3,
      with main contributions from HDL lipoprotein particles in the positive direction
      and small/medium LDL and large IDL particles in the negative direction, was
      associated with a 9% reduction in CAC odds (P<0.05 in 88% of BSA). PC1, which had
      approximately even contributions from HDL, LDL, IDL and VLDL lipoprotein
      subfractions in the positive direction, was not associated with CAC. CONCLUSION:
      In a relatively young but high-risk population, a lipoprotein profile
      predominated by triglyceride-rich lipoproteins was associated with increased risk
      of CAC, while one predominated by HDL lipoproteins offered modest protection.
      Lipoprotein sub-fraction analysis may help to further discriminate patients who
      require more intensive cardiovascular work-up and treatment.

PMID- 30224607
TI  - Mechanism and Management of Cancer Chemotherapy-Induced Atherosclerosis.
AB  - The advent of new chemotherapeutic and immunotherapeutic treatments has markedly
      improved outcomes in patients with cancer. However, increasing numbers of elderly
      patients with cancer and prolonged periods of treatment have made the management
      of cardiovascular complications and treatment-induced cardiotoxicity an important
      concern, and onco-cardiology has received increasing attention. The number of
      patients with cardiotoxicity, particularly atherosclerotic lesions, and the usage
      of angiogenesis inhibitors have increased, making the involvement of onco
      cardiologists essential for effective disease management. A paradigm shift in
      immunotherapy was caused by the development of immune checkpoint inhibitors.
      Because vascular endothelial growth factors (VEGF) in the cancer microenvironment
      and cancer immune function are interrelated angiogenesis inhibitors will most
      likely play an increasingly important role in combined immunotherapy. To ensure
      the optimal long-term diagnosis and long-term treatment of cancer and the
      effective management of treatment-related atherosclerotic diseases, the long-term
      continuous participation of onco-cardiologists is essential.

PMID- 30224608
TI  - The effect of diet control on puberty onset and immunoreactivity of kisspeptin
      and neurokinin B in female rats.
AB  - Early onset puberty and irregular estrous cycles occur more frequently in rats
      which are fed a high-fat diet. Kisspeptin is an essential factor for the
      regulation of sexual maturation and is co-expressed with neurokinin B in neurons
      in the hypothalamic arcuate nucleus. However, the effects of a diet change on
      kisspeptin neuronal signaling are not well-understood. Therefore, in this study,
      we examined the immunoreactivity pattern of the kisspeptin/kiss1-receptor
      (KISS1R) and neurokinin B/neurokinin3-receptor (R). Pups born to high-fat diet
      rats were exposed to a high-fat diet until the onset of puberty. From puberty,
      the offspring originally exposed to a high-fat diet were fed a normal diet up to
      85 postnatal days (PND 85). We examined kisspeptin/Kiss1-receptor and neurokinin
      B/neurokinin3-receptor immunoreactivity (IR) in the arcuate nucleus of the pups.
      The onset of puberty in the high-fat group was significantly earlier than the
      control group. At the onset of puberty, the densities of kisspeptin and
      neurokinin B IR cells were significantly higher in the high-fat diet group than
      in the control group; however, the densities of KISS1 and neurokinin 3-receptor
      IR cells did not differ between the two groups. At PND 85, the density of
      kisspeptin and neurokinin B IR cells did not differ between control and high fat
      group. The density of densities of KISS1 and neurokinin 3-receptor IR cells also
      did not differ between groups at this stage. These data suggest that a high-fat
      diet can influence puberty onset and the immunoreactivity of kisspeptin and
      neurokinin B. These effects can be modified by dietary control.

PMID- 30224609
TI  - Three-dimensional Analysis and Evaluation in Orthognathic Surgical Cases with
      Facial Asymmetry.
AB  - Two-dimensional cephalometric analysis is commonly used in planning and
      evaluating the outcome of orthognathic surgery. It is difficult to arrive at an
      accurate evaluation with this method, however, as the jaw bones overlap in
      profile. Therefore, the purpose of this study was to use 3-dimensional (3-D)
      orthognathic treatment planning software for measurement of distances and angles
      to evaluate change in dentofacial morphology and stability after orthognathic
      surgery in patients with jaw deformity and facial asymmetry. Computed tomography
      with SimPlant O&O(r) (Materialize Dental, Belgium) was used to obtain data at
      before surgery (T1) and at 1 month (T2) and 1-2 years postoperatively (T3).
      Reference points, reference planes, and evaluation items were set to measure
      angles and distances. The average values at T1, T2, and T3 and the standard
      deviations were obtained. The analyses of change in distance and angle between T1
      and T2 in both the maxilla and mandible revealed that the amount of postoperative
      deviation and change was greatest in the mandible (p<0.05). These findings showed
      a correlation between postoperative change in position of the chin and symmetry.
      Only a minimal amount of change was observed between T2 and T3 in both the
      maxilla and mandible. The results also revealed a correlation between positional
      change in both the proximal and distal bone segments and stability. It was found
      to be possible to determine change in horizontal, vertical, and
      anterior/posterior angle in both the maxilla and mandible by such 3-D analysis.
      The results suggest that the chin is the most appropriate facial element for
      evaluation of symmetry after orthognathic surgery.

PMID- 30224610
TI  - Evaluation of Factors Associated with Tongue Coating Status in Elderly with Care
      Needs.
AB  - The tongue surface in older people requiring nursing care is often coated with a
      layer believed to comprise, keratinized products of degeneration, food residue,
      bacteria, and leukocytes attached to the tongue papillae. Which factors affect
      the status of this tongue coating remain to be elucidated, however. The purpose
      of this study was to evaluate factors related to tongue coating status in older
      people requiring nursing care. The study participants comprised 41 individuals
      admitted to special nursing homes for the elderly. After undergoing tooth
      brushing and tongue cleaning by the facility staff, the participants were
      required to refrain from oral cleaning until evaluation of tongue coating status,
      which was performed just after lunch. The moisture level of the tongue surface
      was measured and total number of oral microbes determined. Food type, care level,
      and sex were determined by a questionnaire given by the attending nurses.
      Correlations between the tongue coating status and various factors were analyzed
      using Spearman's rank correlation coefficient. The participants were divided into
      2 groups according to the median value of the tongue coating status. Factors
      related to tongue coating were analyzed using binomial logistic regression
      analysis (alpha=0.05). Tongue coating status showed a significant correlation
      with the total number of oral microbes on the tongue surface (rS=0.449, p=0.003),
      type of food (rS=0.388, p=0.012), and care level (rS=-0.308, p=0.050). Logistic
      regression analysis revealed that the food type of the side dish significantly
      affected tongue coating status. These results showed a correlation between tongue
      coating status and type of food of the side dish in older people requiring
      nursing care.

PMID- 30224611
TI  - Development of Jaw and Deciduous Teeth in Japanese Children -Comparing Size of
      Crown and Alveolar Area between Today and 40 Years Ago.
AB  - The purpose of the present study was to investigate change in the size of the jaw
      and deciduous teeth in Japanese children over the past 40 years by performing
      measurements on plaster models of the dental arch obtained from children born
      between 2007 and 2009 (2000s group) and children born between 1968 and 1974 (70s)
      group. A total of 61 children were enrolled in the 2000s group, comprising 25
      boys (average age, 4 years 5 months) and 36 girls (average age, 4 years 4
      months), and 93 children in the 70s group, comprising 45 boys (4 years 6 months)
      and 48 girls (4 years 4 months). The mesiodistal width of the crown, dental arch
      width, dental arch length, dental arch height, and available arch length in these
      groups were measured using a 3D measurement system and the sums of the
      mesiodistal width of the crown and tooth size-arch length discrepancies
      calculated. The results of the two groups were statistically compared and the
      following conclusions reached: the size of deciduous teeth has not changed
      statistically over the last 40 years; the size of the dental arch has decreased
      in boys (p<0.01), while remaining approximately the same in girls; and the tooth
      size-arch length discrepancy has decreased, especially in boys (p<0.01). These
      results indicate that the interdental spaces of the deciduous dentition have
      decreased, increasing the risk of crowding in Japanese children.

PMID- 30224612
TI  - Growth of Palate in Unilateral Cleft Lip and Palate Patients Undergoing Two-stage
      Palatoplasty and Orthodontic Treatment.
AB  - The purpose of this study was to investigate the long-term effects of two-stage
      palatoplasty on the morphology of the maxillary alveolar arch and occlusion using
      plaster models of the maxilla and mandible obtained from patients with unilateral
      complete cleft lip and palate who also underwent orthodontic treatment. A total
      of 20 patients undergoing two-stage palatoplasty by Perko's method (Group T) were
      enrolled. Plaster models of the maxilla and mandible were obtained from each
      patient at Time 1, on commencement of orthodontic treatment in the mixed
      dentition period; at Time 2, on that of orthodontic treatment in the permanent
      dentition period; and at Time 3, on completion of active orthodontic treatment.
      Analysis of occlusion and morphological analysis were performed using a 3
      dimensional measuring system. The results were compared with 15 patients who
      underwent one-stage palatoplasty by the push-back method using a mucoperiosteal
      flap (Group P). Alveolar morphology and the relationship between the maxilla and
      mandible were satisfactory in Group T. The palates in Group T were deeper and
      larger than those in Group P. Alveolar collapse in Group T was milder, and
      impairment of the alveolar morphology less notable than in Group P, as surgical
      invasion to the anterior alveolar region was avoided during the palatal growth
      period. These results suggest that two-stage palatoplasty is advantageous for jaw
      development.

PMID- 30224613
TI  - Verruciform Xanthoma with Equivocal Exfoliative Cytological Diagnosis.
AB  - Verruciform xanthoma (VX), a papillary or wart-like lesion of the mucosa, is
      histopathologically characterized by papillary projection of the epithelium and
      an aggregation of foam cells in the lamina propria. Here, we describe a case of
      VX in the posterior mandibular gingiva, initially suspected to be a benign lesion
      based on clinical findings and cytology prior to an excisional biopsy. The
      patient was a 62-year-old man who had visited a local dentist approximately 1
      year earlier, presenting with a white lesion in the left posterior mandibular
      gingiva that resisted removal by scraping. The lesion was left untreated as there
      were no subjective symptoms. Thereafter, the surface of the lesion roughened and
      the patient was referred to our department for a comprehensive examination. A
      circumscribed, granular mass, 15-mm in diameter, with a red and white surface was
      observed in the left posterior mandibular buccal gingiva. Exfoliative cytology
      was performed. The diagnosis was a class III lesion. Excisional biopsy was
      performed under local anesthesia. Histopathological examination led to a
      diagnosis of VX. At 1 year postoperatively, the patient is making satisfactory
      progress without recurrence. Verruciform xanthoma is difficult to diagnose
      preoperatively, and is commonly resected under a clinical diagnosis of papilloma
      or benign tumor. A benign lesion was also initially suspected in the present case
      and cytological analysis performed to confirm absence of malignancy. The lesion
      could not be diagnosed as VX preoperatively. Verruciform xanthoma can be over
      diagnosed based solely on cytological examination because it often involves
      cellular atypia reflecting its characteristic extension of rete pegs and
      keratinization of surface cells, indicating the need for care in arriving at a
      definitive diagnosis.

PMID- 30224614
TI  - Implant-supported Prostheses in Patient with Sjogren's Syndrome: Clinical Report
      with 3-year Follow-up.
AB  - Sjogren's syndrome (SS), an autoimmune disorder, affects the exocrine glands,
      including the lacrimal and salivary glands. It is characterized by symptoms of
      dry eye and dry mouth. As secretion of saliva decreases, patients with SS
      experience rampant caries, pain in the oral mucosa, inflammation and hardening of
      the salivary glands, abnormal taste, dysphagia, and loss of teeth earlier than
      healthy individuals. A removable partial denture is often used as a prosthesis
      after tooth loss. Compromised salivary lubrication, however, can produce
      traumatic ulceration of the mucosa, making use of a removable prosthesis in SS
      patients painful. In such cases, a dental implant is likely to be requested as an
      alternative. This report describes dental implant treatment in an SS patient, a
      50-year-old woman who presented with the chief complaint of masticatory
      dysfunction and pain due to a removable partial denture. Eight implants were
      placed in the maxillary and mandibular first molar tooth and second molar tooth
      regions. Following a 4-month non-loading period, second-stage surgery and
      provisional restoration with a screwretained implant temporary crown were
      performed. Screw-retained superstructures were fitted by means of a customized
      titanium abutment and zirconia crown as the final restoration. No complications,
      including inflammation of peri-implant soft tissue or resorption of peri-implant
      bone, were observed at 3 years following placement of the superstructures.

PMID- 30224615
TI  - Atypical MRI and Histopathological Findings in Dermoid Cyst.
AB  - On images, a dermoid cyst is often described as resembling a "sack of marbles" or
      "marbles in a bag". Typically, it comprises an inhomogeneity filled with multiple
      nodules in a fluid matrix on both computed tomography and magnetic resonance
      imaging (MRI). How it appears, however, will vary depending on its histological
      contents, which may cause confusion in arriving at a diagnosis. This report
      describes a dermoid cyst in the floor of the mouth of a 55 year-old woman that
      showed an atypical internal appearance on MRI. Most of the lesion showed
      homogeneous high signal intensity on T1 - and T2-weighted images, suggesting that
      it was derived from fat. A small area within the mass, however, showed moderate
      signal intensity almost equal to that of muscle on T1-weighted images and high
      signal intensity on fat-suppressed T2-weighted images. Given the location of the
      lesion, a dermoid cyst was one possible diagnosis. A lipoma or lipoma variants
      were also considered, however, based on signal intensity. Histopathological
      section of the excised specimen revealed a dermoid cyst with sebaceous glands in
      its walls and keratin in its cavity. Dermoid cysts show variation in their
      internal structures and contents. Since MRI can reflect such histological
      variation, signal intensity requires careful interpretation.

PMID- 30224616
TI  - Two-year Survey of Trends at Food Introduction Booth at Suidobashi Hospital of
      Tokyo Dental College.
AB  - A working group established at Tokyo Dental College Suidobashi Hospital
      considered how to manage patients experiencing difficulties with food intake
      during the process of dental treatment. This resulted in the opening of an in
      hospital booth dedicated to providing advice on such problems. A survey was
      performed to determine the number of patients utilizing this facility and the
      department which they were attending with the aim of investigating factors
      involved in eating-related problems. The results revealed that patients were
      being referred to the booth from the departments of dental prosthetics,
      conservative dentistry, oral and maxillofacial surgery (by both dentists and
      dietitians), oral implantation, and orthodontics. Patients were provided with
      information on the booth by their dentist or dietician, either by means of
      introductory materials or verbally. These patients were requested to complete a
      questionnaire, with informed consent, over a 2-year period. The participants were
      classified according to age and original dental problem on attending this
      hospital and the results analyzed. The inability to eat hard foodstuffs,
      difficulty in chewing, inability to open the mouth, insufficient nutrition,
      unbalanced nutrition, intraoral pain, and difficulty in swallowing were all
      identified as problems related to eating. A total of 1,948, 413 visitors had
      received introductory materials, while 156 had learned of the facility verbally.
      Looking at department as a factor, the inability to eat hard foodstuffs and
      difficulty chewing occupied a large percentage of the reported problems for all
      departments. Taken together, these results revealed that many patients
      experienced difficulties in eating during the process of treatment. This
      indicates that it is necessary to give the appropriate eating instructions to
      each patient according to their specific needs and stage of dental treatment.

PMID- 30224617
TI  - Preparation of 1L-myo-Inositol 1-Phosphate as a Substrate of Phosphatidylinositol
      Phosphate Synthase.
AB  - Novel drugs possessing a mechanism of action specific to pathogenic mycobacteria,
      including Mycobacterium tuberculosis, are needed. In 2010, we discovered that the
      biosynthetic pathway of phosphatidylinositol, which is a membrane phospholipid,
      differs between humans and mycobacteria. The key enzyme responsible for this
      difference is phosphatidylinositol phosphate (PIP) synthase, which is present
      only in a few bacteria belonging to the phylum Actinobacteria. Discovering
      compounds that inhibit the activity of this enzyme will lead to the development
      of new drugs specific to pathogenic mycobacteria. Measuring PIP synthase activity
      requires the isotope-labeled substrate 1l-myo-inositol 1-phosphate (1l-Ino-1P).
      Because this substrate is not commercially available, we synthesized it from
      [14C] glucose 6-phosphate ([14C] Glc-6P), using a crude enzyme solution isolated
      from the methanoarchaeon 1l-Ino-1P synthase. The activity of 1l-Ino-1P synthase
      in the crude enzyme mixture was low, and quantitative analysis of the synthesized
      1l-Ino-1P was inaccurate due to impurities present in the crude enzyme mixture.
      In the present study, we describe a method for synthesizing 1l-Ino-1P using a
      solution containing recombinant 1l-Ino-1P synthase derived from the
      hyperthermophilic archaeon Aeropyrum pernix. In addition, we elucidate the
      conditions leading to the almost complete conversion of Glc-6P into 1l-Ino-1P
      using this enzyme. Quantitation of the synthesized 1l -Ino-1P was performed by
      colorimetry and gas liquid chromatography. Further, we confirmed that isotope
      labeled 1l-Ino-1P, which is difficult to quantitate by gas liquid chromatography,
      can be accurately quantified by colorimetry. We also confirmed that 1d-inositol 1
      phosphate cannot be a substrate for PIP synthase.

PMID- 30224618
TI  - Health Management of Workers with Presenteeism is a New Challenge in Occupational
      Health.
AB  - There has been a growing interest in presenteeism in recent years in both the
      occupational health and management fields. However, the term "presenteeism" was
      introduced in Japan relatively recently, and only limited knowledge on the
      subject has since been accumulated. This review will outline the current
      knowledge on presenteeism and discuss the significance of addressing presenteeism
      in occupational health in Japan. A common definition of presenteeism is the state
      that showing up at the office while having health problems, and some have added a
      decline in productivity. Several methods have been proposed to convert a degree
      of presenteeism into monetary value in terms of a health economics perspective,
      but there is no consistent method. A new approach is needed to evaluate and
      support workers who are experiencing presenteeism.

PMID- 30224619
TI  - A Pediatric Case of Graves' Hyperthyroidism with Associated Glucose Intolerance
      Detected by a Urine Glucose Screening Program at School.
AB  - We report here a 13-year-old female with Graves' disease, whose diagnostic clue
      was glycosuria, which was detected by a urine glucose screening program at
      school. She had had mild general malaise, and a physical examination revealed a
      slightly enlarged thyroid gland. Hyperthyroidism (thyroid-stimulating hormone
      (TSH) < 0.01 MUU/ml, free triiodothyronine (fT3) 23.57 pg/ml, free thyroxine
      (fT4) 3.38 ng/dl) and anti-thyroid autoantibodies (TRAb 43.6%) were detected in
      laboratory tests, and her plasma glucose at 120 minutes was 142 mg/dl in a 75 g
      oral glucose tolerance test. She was diagnosed as having borderline diabetes.
      These findings revealed a diagnosis of Graves' hyperthyroidism with associated
      impaired glucose tolerance. Although it is reported that many adults with
      hyperthyroidism develop disorders of glucose metabolism, pediatric patients
      rarely have complications of glucose intolerance or diabetes mellitus, and there
      are no previous reports of Graves' disease diagnosed by a urine glucose screening
      program at school. This case suggests a possibility of abnormalities in glucose
      metabolism even in pediatric cases of Graves' disease. To avoid overlooking the
      diagnosis of glucose intolerance associated with hyperthyroidism, a careful
      medical interview and examination should be performed even if the clinical
      features are mild.

PMID- 30224620
TI  - Thoracoscopic Lung Lobectomy for a Lung Cancer Patient with Situs Inversus
      Totalis.
AB  - Situs inversus totalis is a rare clinical condition that represents a complete
      mirror image of the normal arrangement of the thoracic and abdominal viscera.
      There are very few reported cases of lung cancer patients with situs inversus
      totalis, but this condition requires particular care during surgery. A 61-year
      old woman presented to our hospital with an abnormal shadow on chest radiography.
      Computed tomography revealed a 25*12 mm solitary pulmonary nodule in the left
      upper lobe (S2) and a complete mirror image of the normal organ arrangement,
      which findings met the criteria of situs inversus totalis. Preoperative
      examination revealed left upper lobe lung cancer (c-T1bN0M0 Stage IA), and
      surgery was planned for diagnosis and treatment. Before the surgery, three
      dimensional CT images were reconstructed for a precise evaluation of the
      pulmonary vessels and bronchi. The nodule was microscopically diagnosed as
      adenocarcinoma from a frozen section obtained by wedge resection. We performed a
      left upper lobectomy with lymph node dissection using video-assisted thoracic
      surgery. The aortic arch was absent from the left thoracic cavity and the left
      lung was well lobulated into three lobes. Although it revealed a mirror image of
      the usual arrangement, we could accomplished in the usual procedure and process.
      Careful preoperative anatomical evaluation and perioperative handling are
      essential for the prevention of intraoperative injuries and complications in
      patients with situs inversus totalis.

PMID- 30224621
TI  - [On English Multiple Discourse-Related Movement].
AB  - In light of the cartographic Complementizer Phrase (CP) analysis, in which two
      computationally requisite functional projections (i.e., Force Phrase: ForceP and
      Finite Phrase: FinP) sandwich two optional discourse-related projections (i.e.,
      Topic Phrase: TopP and Focus Phrase: FocP) in the clause-peripheral domain, it is
      theoretically reasonable to postulate the former as phase, a basic computational
      unit assumed in recent minimalist syntactic theory. We call this hybrid-type of
      syntactic analysis Phase-based CP Cartographic Analysis. Using this, we
      investigate multiple discourse-related movement (MDM) phenomena in English,
      including Topicalization, Focalization and Wh-movement at the clausal periphery.
      Our approach can appropriately capture the grammaticality regarding word order,
      which is derived from the combination of these clause-peripheral movements.

PMID- 30224622
TI  - [Evaluation of Clinical Features and Growth Hormone Deficiency in Short Children
      Born Small For Gestational Age].
AB  - Growth hormone (GH) therapy for short children born small for gestational age
      (SGA) has been approved in Japan. It is important to evaluate GH secretion
      ability before the initiation of GH therapy because there are some differences in
      dose and medical expenses between short children born SGA and GH deficiency
      (GHD). This study was designed to elucidate the incidence of GHD and to find a
      useful marker for detecting it in short SGA children. We retrospectively reviewed
      medical records to analyze the clinical features of short children born SGA and
      with GHD who had started GH therapy before the age of 6 in the University
      Hospital of Occupational and Environmental Health and Kyushu Rousai Hospital.
      Nine of 22 SGA subjects (41%) had GHD. There were no significant differences
      between two groups of short SGA children (GHD, non-GHD) in the median of height
      and serum insulin-like growth factors (IGF)-1 levels at birth or at the start of
      GH therapy. The probability of GHD was higher if the height standard deviation
      scores (SD) of the SGA children were lower than -3.2 (odds ratio, 11.6; 95%
      confidence interval, 1.52 - 89.1, P = 0.013). This study showed that there is an
      approximately 40% incidence of GHD in short SGA children needing GH treatment. We
      should do GH stimulation tests for short SGA children whose height SD is lower
      than -3 to determine the appropriate GH therapy.

PMID- 30224623
TI  - [A Case of Carcinoma Showing Thymus-Like Differentiation (CASTLE) of the
      Thyroid].
AB  - The case presented herein was a 70-year-old woman who had no compliant, but had a
      mass in the lower part of the right lobe of the thyroid detected by ultrasound
      (US). The US image of the tumor, measuring 13 mm in diameter, showed a low and
      heterogeneous internal echo level with calcification and an irregular margin. The
      tumor appeared to extend to the adjacent sternothyroid muscle, and cervical lymph
      node swelling was detected in a computer tomography (CT) image, but no metastatic
      lesion was found by positron emission tomography (PET)-CT. In a fine needle
      aspiration cytology of the tumor, papillary thyroid carcinoma was suggested
      because of the atypical epithelial cells having some changes other than
      intranuclear inclusion bodies. A subtotal thyroidectomy and central neck lymph
      node dissection were performed. The excised tumor was histologically composed of
      irregular nests or sheets of atypical squamoid epithelial cells with some ductal
      structures that leached to the sternothyroid muscle and involved the right lower
      parathyroid gland. Carcinoma showing thymus-like differentiation (CASTLE) was
      diagnosed histopathologically and immunohistochemically with the following
      immunohistochemical results: Cluster of differentiation 5 (CD5) (+), tumor
      protein p63 (p63) (+), KIT proto-oncogene receptor tyrosine kinase (c-KIT(CD117))
      (+), thyroglobulin (-), and thyroid transcription factor-1 (TTF-1) (-). CASTLE is
      a rare carcinoma of the thyroid that architecturally resembles thymic epithelial
      tumors. Many CASTLE patients have been misdiagnosed as other carcinomas, such as
      anaplastic carcinoma, poorly differentiated carcinoma or squamous cell carcinoma
      of the thyroid. Immunohistochemical examination, including CD5 played an
      important role in the final diagnosis of CASTLE, although the distinction from
      diagnosis as squamous cell carcinoma or mucoepidermoid carcinoma in Hematoxylin
      Eosin staining was challenging in our case. Nodal metastasis and perithyroidal
      tumor extension of CASTLE can predict its worse prognosis. Thus, at least careful
      follow-up studies are mandatory in cases of CASTLE.

PMID- 30224624
TI  - [Current Status and Issues of the Pre-Clinical Training OSCE in Acute Care
      Nursing Education].
AB  - Enabling students to acquire practical skills that can be utilized after
      graduation has become an agenda for basic nursing education since the start of
      Japan's "super-aging society" and the sophistication of modern medical treatment.
      Nursing schools are attempting to introduce the Objective Structured Clinical
      Examination (OSCE) in an attempt to integrate this important agenda. OSCE has
      been implemented at our school of nursing since 2014 in the first semester for
      third year students as a part of the integrated course for clinical training. E
      learning has been utilized to help students study for the examination, and,
      according to students' subjective evaluations, a certain level of effect has been
      confirmed. However, as we have new agendas for each school year, adjustments need
      to be made every year. We have made 3 adjustments so far since 2017. In this
      paper we report on our implementation of the OSCE in the year 2014, evaluations
      and adjustments to the OSCE in 2014 from the perspectives of 1) learning support,
      2) evaluation methods, and 3) the application of the OSCE.

PMID- 30224625
TI  - [Announcement of the 36th Annual Meeting of the UOEH Association of Health
      Sciences].

PMID- 30224626
TI  - Anticancer Activity of Phloretin Against Human Gastric Cancer Cell Lines Involves
      Apoptosis, Cell Cycle Arrest, and Inhibition of Cell Invasion and JNK Signalling
      Pathway.
AB  - BACKGROUND Gastric cancer is one of most commonly diagnosed cancers and causes
      significant mortality worldwide. In this study, the antiproliferative and
      anticancer effects of Phloretin were evaluated against gastric cancer cell lines.
      MATERIAL AND METHODS MTT assay was used to assess the proliferation rate of
      gastric cancer cells. DAPI and annexin V/PI were used for detection of apoptotic
      cell death. Cell invasion was investigated by Transwell assays and the expression
      of the proteins was estimated by immunoblotting. RESULTS The results revealed
      that Phloretin exerts anticancer effects on all the gastric cancer cell lines
      used in this study. However, the anticancer effects were more significant
      (p<0.05) on the AGS cell line. Further, the effect of Phloretin on the viability
      of normal GES-1 cells was minimal. Apoptosis assays showed that Phloretin
      triggers apoptotic cell death in AGS gastric cancer cells. Phloretin could also
      cause the arrest of the AGS gastric cancer cells in the G2/M phase of the cell
      cycle and suppress their ability to migrate. Western blotting analysis revealed
      that Phloretin significantly decreased the expression of p-JNK and p-38. However,
      comparatively lower effects were observed on the expression of JNK and P38.
      CONCLUSIONS We showed that Phloretin is an important molecule for the treatment
      of gastric cancer.

PMID- 30224627
TI  - Strategies to Improve Patient Engagement in Young Kidney Transplant Recipients: A
      Review.
AB  - Young adult and adolescent kidney transplant recipients have shorter graft
      survival than older and younger recipients. Although multifactorial, the tendency
      toward premature graft loss in young kidney transplant recipients has often been
      attributed to medication nonadherence and the transition from pediatric to adult
      care. Multiple interventions for medication nonadherence in kidney transplant
      recipients have been studied. Potential preventative interventions include pre
      transplant screening, transition and young adult clinics, technologies such as
      reminders or mobile applications, and simplification of the post-transplant
      medication regimen. There are also recent advances in monitoring interventions
      for nonadherence in transplant recipients, including electronic monitoring
      devices such as wireless pill bottles and the Ingestible Sensor System, which
      incorporates ingestible microsensors into medications. Treatment interventions
      for medication nonadherence include cognitive behavioral programs, behavioral
      contracts, and screening and treatment for depression. Several of the
      interventions reviewed are currently available to providers caring for young
      kidney transplant recipients, without any complex programmatic changes. Further
      research in all of these areas would be of great value.

PMID- 30224628
TI  - Emergence of Ventricular Septal Rupture During Primary Coronary Intervention for
      Myocardial Infarction Manifested as Unexpected Coronary Blood Flow Disturbance.
AB  - BACKGROUND As primary percutaneous coronary intervention (PCI) has been commonly
      performed for acute myocardial infarction (AMI), we rarely encounter ventricular
      septal rupture (VSR), which is one of the mechanical complications of AMI.
      However, the associated mortality rate is still very high unless treated
      appropriately. CASE REPORT We encountered a very rare case of VSR that was
      considered to have occurred during primary PCI for AMI. The manifestation of
      sudden coronary flow disturbance may correspond with the emergence of VSR. We
      introduced a veno-arterial extracorporeal membrane oxygenation (ECMO) system for
      sudden hemodynamic instability. As a result, the existence of VSR under the
      operation of the ECMO system led to unusual hemodynamics in the heart, but the
      vital signs were stabilized by ECMO. VSR was surgically treated and the patient
      fully recovered without any neurological or physical sequelae. CONCLUSIONS
      Although we now encounter markedly fewer mechanical complications of AMI in this
      era of primary PCI, we should always be conscious of its possibility in the acute
      phase of myocardial infarction.

PMID- 30224630
TI  - Author Correction: Eya3 partners with PP2A to induce c-Myc stabilization and
      tumor progression.
AB  - In the original version of this Article, the title of the legend to Fig. 7
      incorrectly read 'Knockdown of B55alpha increases breast cancer metastasis'
      instead of 'Knockdown of B55alpha decreases breast cancer metastasis'. This has
      now been corrected in both the PDF and HTML versions of the Article.

PMID- 30224629
TI  - Recurrent WNT pathway alterations are frequent in relapsed small cell lung
      cancer.
AB  - Nearly all patients with small cell lung cancer (SCLC) eventually relapse with
      chemoresistant disease. The molecular mechanisms driving chemoresistance in SCLC
      remain un-characterized. Here, we describe whole-exome sequencing of paired SCLC
      tumor samples procured at diagnosis and relapse from 12 patients, and unpaired
      relapse samples from 18 additional patients. Multiple somatic copy number
      alterations, including gains in ABCC1 and deletions in MYCL, MSH2, and MSH6, are
      identifiable in relapsed samples. Relapse samples also exhibit recurrent
      mutations and loss of heterozygosity in regulators of WNT signaling, including
      CHD8 and APC. Analysis of RNA-sequencing data shows enrichment for an ASCL1-low
      expression subtype and WNT activation in relapse samples. Activation of WNT
      signaling in chemosensitive human SCLC cell lines through APC knockdown induces
      chemoresistance. Additionally, in vitro-derived chemoresistant cell lines
      demonstrate increased WNT activity. Overall, our results suggest WNT signaling
      activation as a mechanism of chemoresistance in relapsed SCLC.

PMID- 30224631
TI  - Low fasting plasma glucose level as a predictor of new-onset diabetes mellitus on
      a large cohort from a Japanese general population.
AB  - Although fasting plasma glucose levels <70 mg/dL are associated with a high
      incidence of cardiovascular disease (CVD), whether there is any risk of new-onset
      diabetes mellitus owing to fasting plasma glucose at this range has not been
      clarified. We measured the odds ratio (OR) of new-onset diabetes mellitus
      relative to fasting plasma glucose levels at various ranges in a nation-wide
      Japanese population with and without CVD history. Of 186,749 participants without
      diabetes in 2008, 171,408 had no history of CVD, while 15,341 did. Participants
      were classified into 8 categories according to their fasting plasma glucose
      levels. Unadjusted and multivariable-adjusted logistic regression models were
      used to measure the OR of new-onset diabetes mellitus in the 3-year follow up. In
      all participants, multivariable-adjusted OR increased when fasting plasma glucose
      levels were <70 mg/dL or 90-125 mg/dL. Participants without CVD showed increased
      OR when glucose levels were <70 mg/dL or 90-125 mg/dL. Participants with a
      history of CVD showed increased OR with glucose levels of 95-125 mg/dL. The risk
      of new-onset diabetes mellitus is higher when fasting glucose levels are <70
      mg/dL, indicating that the paradox of fasting glucose seeks a new risk
      stratification for new-onset diabetes mellitus.

PMID- 30224632
TI  - Multilayer homogeneous dielectric filler for electromagnetic invisibility.
AB  - In recent years, invisibility has become a research area of increasing interest
      due to the advances in material engineering. It may be possible to achieve
      invisibility through cloaking devices by coating the body using one or more
      layers of materials with the proper electromagnetic properties. By using
      techniques associated to plasmonic cloaking it is maybe possible to obtain also
      invisibility for small objects with several layers of homogeneous materials
      working from inside the object. We demonstrate numerically that it is, therefore,
      possible to achieve invisibility through an inner system based on scattering
      cancellation techniques.

PMID- 30224633
TI  - Human-like smelling of a rose scent using an olfactory receptor nanodisc-based
      bioelectronic nose.
AB  - We report a strategy for the human-like smelling of a rose scent utilizing
      olfactory receptor nanodisc (ND)-based bioelectronic nose devices. In this
      strategy, a floating electrode (FE)-based carbon nanotube (CNT) field effect
      transistor (FET) was functionalized with human olfactory receptor 1A2 (hOR1A2)
      embedded NDs (hOR1A2NDs). The hOR1A2NDs responded to rose scent molecules
      specifically, which were monitored electrically using the underlying CNT-FET.
      This strategy allowed us to quantitatively assess the contents of geraniol and
      citronellol, the main components of a rose scent, as low as 1 fM and 10 fM,
      respectively. In addition, it enabled us to selectively discriminate a specific
      rose odorant from other odorants. Significantly, we also demonstrated that the
      responses of hOR1A2NDs to a rose scent could be strongly enhanced by enhancer
      materials like a human nose. Furthermore, the method provided a means to
      quantitatively evaluate rose scent components in real samples such as rose oil.
      Since our method allows one to quantitatively evaluate general rose scent
      ingredients just like a human nose, it could be a powerful strategy for versatile
      basic research and various applications such as fragrance development.

PMID- 30224634
TI  - Asymmetric-Fluidic-Reservoirs Induced High Rectification Nanofluidic Diode.
AB  - We demonstrate a novel nanofluidic diode that produces rectification factors in
      excess of 1000. The nanofluidic diode consists of ion permselective nanopores
      that connect two reservoirs of different diameters- a micropore reservoir and a
      macropore reservoir. On the application of +100 V to the micropore, a low OFF
      state current is observed. The OFF state is caused by formation of the ion
      depleted zone in the micropore because the anions are prevented from entering the
      nanopores from the micropore and the cations are depleted in this region to
      maintain charge neutrality. On the application of -100 V, we observe a high ON
      state current. The ON state is caused by formation of the ion enriched zone in
      the microchannel because the anions cannot pass through the nanopores and
      accumulate in the microchannel. To maintain charge neutrality the cations also
      become enriched in the microchannel. The ratio of ON state current to the OFF
      state current gives the rectification of current. Here, plasma oxidation is used
      to achieve a nanopore with a large wall surface charge density of sigman = -55
      mC/m2 which yields a rectification of current on the order of 3500 that is nearly
      two orders of magnitude higher than those reported thus far. In contrast to the
      other nanofluidic diodes, this nanofluidic diode does not introduce asymmetry to
      the nanopore, but asymmetry is produced by having the nanopores join a micropore
      and a macropore. Introduction of asymmetry into the fluidic reservoirs which the
      nanopores connect is quite simple. Hence, the nanofluidic diode is easy to scale
      up to industrial level.

PMID- 30224635
TI  - Oxidative DNA damage induced by ROS-modulating agents with the ability to target
      DNA: A comparison of the biological characteristics of citrus pectin and apple
      pectin.
AB  - DNA targeting anticancer agents have been very successful in clinic, especially,
      when used in combinatorial therapy. But unfortunately, they often exhibit high
      levels of toxicity towards normal cells. Hence, much effort has been put into
      finding agents with more selectivity, and less toxicity. Pectins are natural
      polysaccharides, and beneficial nutritional fibers that have attracted attentions
      due to their antitumor properties. However, their molecular targets, and
      mechanism of action are widely unknown. Here, we have reported that citrus pectin
      (CP) and apple pectin (AP) selectively suppress viability in MDA-MB-231, MCF-7
      and T47D human Breast cancer cells, while non-toxic to L929 normal cells. Upon
      CP, and AP treatments, cancer cells' ROS content increased rapidly, and led to
      the collapse of the mitochondrial transmembrane potential which functions
      upstream of the caspase-dependent apoptosis. CP and AP treated cancer cells were
      also arrested at the S and G1 or G2/M phases of the cell cycle, respectively.
      Furthermore, mRNA expression of Galectin-3 (a multi-functional lectin involved in
      cell adhesion, cell cycle, and apoptosis) reduced in both CP and AP treated
      cells. Growth inhibition of MDA-MB-231 cells by CP, and AP was concomitant with
      DNA damage (oxidation, and strand breaks). In this context, in an effort to
      clarify the mechanism of action, we showed that CP, and AP are able to interact
      with DNA. The strength and mode of DNA binding were established by spectroscopy
      techniques. We demonstrated that CP, and AP bind to dsDNA by intercalation, and
      groove binding/partial intercalation, respectively. In conclusion, our findings
      suggest that CP, and AP induce apoptosis in MDA-MB-231 cells by increasing the
      release of ROS, which may be related to the mitochondrial apoptosis pathway, and
      direct interactions with DNA. Our data indicate that these compounds may be
      potentially useful in cancer treatment.

PMID- 30224636
TI  - CUDC-907 displays potent antitumor activity against human pancreatic
      adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c
      Myc expression.
AB  - Pancreatic adenocarcinoma is a highly malignant cancer that often involves a
      deregulation of c-Myc. It has been shown that c-Myc plays a pivotal role in the
      regulation of a variety of physiological processes and is involved in early
      neoplastic development, resulting in poor progression. Hence, suppression of c
      Myc overexpression is a potential strategy for pancreatic cancer therapy. CUDC
      907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and
      histone deacetylase (HDAC). It has shown potential efficiency in patients with
      lymphoma, multiple myeloma, or thyroid cancer, as well as in solid tumors with c
      Myc alterations, but the evidence is lacking for how CUDC-907 regulates c-Myc. In
      this study, we investigated the effect of CUDC-907 on human pancreatic cancer
      cells in vitro and in vivo. Our results showed that CUDC-907 potently inhibited
      the proliferation of 9 pancreatic cancer cell lines in vitro with IC50 values
      ranging from 6.7 to 54.5 nM. Furthermore, we revealed the antitumor mechanism of
      CUDC-907 in Aspc-1, PANC-1, and Capan-1 pancreatic cancer cells: it suppressed
      the HDAC6 subunit, thus downregulating c-Myc protein levels, which was a mode of
      action distinct from the existing mechanisms. Consistently, the extraordinary
      antitumor activity of CUDC-907 accompanied by downregulation of c-Myc and Ki67
      expression in tumor tissue was observed in a human pancreatic cancer Aspc-1
      xenograft nude mouse model in vivo. Our results suggest that CUDC-907 can be a
      valuable therapeutic option for treating pancreatic adenocarcinoma.

PMID- 30224637
TI  - Selective dopamine D3 receptor antagonist YQA14 inhibits morphine-induced
      behavioral sensitization in wild type, but not in dopamine D3 receptor knockout
      mice.
AB  - Increasing preclinical evidence demonstrates that dopamine D3 receptor (D3R)
      antagonists are a potential option for the treatment of drug addiction. The
      reinstatement of the addiction can be triggered by environmental stimuli that
      acquire motivational salience through repeated associations with the drug's
      effects. YQA14 is a novel D3R antagonist that has exhibited pharmacotherapeutic
      efficacy in reducing cocaine and amphetamine reward and relapse to drug seeking
      in mice. In this study we investigated the effects of YQA14 on morphine-induced
      context-specific locomotor sensitization in mice. We showed that repeated
      injection of YQA14 (6.25-25 mg/kg every day ip) prior to morphine (10 mg/kg every
      day sc) not only inhibited the acquisition, but also significantly attenuated the
      expression of morphine-induced locomotor sensitization. Furthermore, in the
      expression phase, one single injection of YQA14 (6.25-25 mg/kg, ip) dose
      dependently inhibited the expression of morphine-induced behavioral
      sensitization. Moreover, YQA14 inhibited the expression of morphine-induced
      behavioral sensitization in wild mice (WT), but not in D3R knockout (D3R-/-) mice
      in the expression phase. In addition, D3R-/- mice also displayed the reduction in
      the expression phase compared with WT mice. In summary, this study demonstrates
      that blockade or knockout of the D3R inhibits morphine-induced behavior
      sensitization, suggesting that D3R plays an important role in the pathogenesis
      and etiology of morphine addiction, and it might be a potential target for
      clinical management of opioid addiction.

PMID- 30224638
TI  - The clinical relevance of necroinflammation-highlighting the importance of acute
      kidney injury and the adrenal glands.
AB  - Necroinflammation is defined as the inflammatory response to necrotic cell death.
      Different necrotic cell death pathways exhibit different immune reponses, despite
      a comparable level of intracellular content release (referred to as damage
      associated molecular patterns or DAMPs). In addition to DAMP release, which is
      inevitably associated with necrotic cell death, the active production of pro/anti
      inflammatory cytokines characterizes certain necrotic pathways. Necroptosis,
      ferroptosis and pyroptosis, therefore, are immunogenic to a different extent. In
      this review, we discuss the clinical relevance of necroinflammation highlighting
      potential human serum markers. We focus on the role of the adrenal glands and the
      lungs as central organs affected by systemic and/or local DAMP release and
      underline their role in intensive care medicine. In addition, data from models of
      acute kidney injury (AKI) and kidney transplantation have significantly shaped
      the field of necroinflammation and may be helpful for the understanding of the
      potential role of dialysis and plasma exchange to treat ongoing necroinflammation
      upon intensive care unit (ICU) conditions. In conclusion, we are only beginning
      to understand the importance of necroinflammation in diseases and
      transplantation, including xenotransplantation. However, given the existing
      efforts to develop inhibitors of necrotic cell death (ferrostatins, necrostatins,
      etc), we consider it likely that interference with necroinflammation reaches
      clinical routine in the near future.

PMID- 30224639
TI  - Autophagy-independent induction of LC3B through oxidative stress reveals its non
      canonical role in anoikis of ovarian cancer cells.
AB  - Cancer cells display abnormal redox metabolism. Autophagy, anoikis and reactive
      oxygen species (ROS) play a regulatory role during metastasis. LC3 is a well
      known essential molecule for autophagy. Therefore, we wanted to explore the
      molecular interplay between autophagy, anoikis, and ROS in relation to LC3B. We
      observed enhanced LC3B level along with increased expression of p62 and
      modulation of other autophagy-related molecules (Atg 3, 5, 7, 12, 16L1 and
      Beclin1) by inducing oxidative-stress in ovarian cancer cells using a ROS
      producing pro-oxidant molecule. Surprisingly, enhanced LC3B was unable to induce
      autophagosome formation rather promoted anoikis. ROS-induced inhibition of
      autophagosome-formation is possibly due to the instability of autophagy
      initiator, ULK1 complex. Moreover, such upregulation of LC3B via ROS enhanced
      several apoptotic molecules. Silencing LC3B reduced these apoptotic molecules and
      increased when overexpressed, suggesting its role in apoptosis. Furthermore, LC3B
      dependent apoptosis was decreased by inhibiting ROS, indicating a possible link
      between ROS, LC3B, and apoptosis. Additionally, ROS-induced enhanced LC3B
      promoted detachment-induced cell death (anoikis). This was further reflected by
      reduced cell adhesion molecules (integrin-beta3 and focal adhesion kinase) and
      mesenchymal markers (snail and slug). Our in vitro experimental data was further
      confirmed in primary tumors developed in syngeneic mice, which also showed ROS
      mediated LC3B enhancement along with reduced autophagosomes, integrin-beta3 and
      focal adhesion kinase ultimately leading to the decreased tumor mass.
      Additionally, primary cells from high-grade serous carcinoma patient's ascites
      exhibited LC3B enhancement and autophagy inhibition through ROS which provided a
      clinical relevance of our study. Taken together, this is the first evidence for a
      non-canonical role of LC3B in promoting anoikis in contrast to autophagy and may,
      therefore, consider as a potential therapeutic target molecule in ovarian cancer.
      Taken together, autophagy-inhibition may be an alternative approach to induce
      apoptosis/anoikis in cancer.

PMID- 30224640
TI  - Evidence for dynamic kagome ice.
AB  - The search for two-dimensional quantum spin liquids, exotic magnetic states
      remaining disordered down to zero temperature, has been a great challenge in
      frustrated magnetism over the last few decades. Recently, evidence for
      fractionalized excitations, called spinons, emerging from these states has been
      observed in kagome and triangular antiferromagnets. In contrast, quantum
      ferromagnetic spin liquids in two dimensions, namely quantum kagome ices, have
      been less investigated, yet their classical counterparts exhibit amazing
      properties, magnetic monopole crystals as well as magnetic fragmentation. Here,
      we show that applying a magnetic field to the pyrochlore oxide Nd2Zr2O7, which
      has been shown to develop three-dimensional quantum magnetic fragmentation in
      zero field, results in a dimensional reduction, creating a dynamic kagome ice
      state: the spin excitation spectrum determined by neutron scattering encompasses
      a flat mode with a six arm shape akin to the kagome ice structure factor, from
      which dispersive branches emerge.

PMID- 30224641
TI  - Shape transformable bifurcated stents.
AB  - Non-invasive delivery of artificial implants, stents or devices in patients is
      vital for rapid and successful recovery. Unfortunately, because the delivery
      passage is often narrower than the size of the delivered object, a compromise
      between the shape that is effective at the targeted location and a thin form that
      allows smooth unobstructed travel to the destination is needed. We address this
      problem through two key technologies: 3D printing and shape memory polymers
      (SMPs). 3D printing can produce patient-customizable objects, and SMPs can change
      their initially formed shape to the final desired shape through external
      stimulation. Using these two technologies, we examine the design and fabrication
      of bifurcated stents. This study presents a mock-up where blood vessels are
      fabricated using moulded silicon, which supports the effectiveness of the
      proposed method. The experimental results reveal that a bifurcated stent with a
      kirigami structure can smoothly travel inside a vessel without being obstructed
      by branched parts. We believe that this work can improve the success rate of
      stent insertion operations in medicine.

PMID- 30224642
TI  - Kondo-like transport and magnetic field effect of charge carrier fluctuations in
      granular aluminum oxide thin films.
AB  - Granular aluminum oxide is an attractive material for superconducting quantum
      electronics. However, its low-temperature normal state transport properties are
      still not fully understood, while they could be related to the unconventional
      phenomenon of the superconductivity in this material. In order to obtain useful
      information on this aspect, a detailed study of charge carrier fluctuations has
      been performed in granular aluminum oxide films. The results of electric noise
      measurements indicate the presence of a Kondo-type spin-flip scattering mechanism
      for the conducting electrons in the normal state, at low temperatures. Moreover,
      the magnetic field dependence of the noise amplitude suggests that interface
      magnetic moments are the main source of fluctuations. The identification of the
      nature of fluctuation processes is a mandatory requirement for the improvement of
      quality and performance of quantum devices.

PMID- 30224643
TI  - Promoter capture Hi-C-based identification of recurrent noncoding mutations in
      colorectal cancer.
AB  - Efforts are being directed to systematically analyze the non-coding regions of
      the genome for cancer-driving mutations1-6. cis-regulatory elements (CREs)
      represent a highly enriched subset of the non-coding regions of the genome in
      which to search for such mutations. Here we use high-throughput chromosome
      conformation capture techniques (Hi-C) for 19,023 promoter fragments to catalog
      the regulatory landscape of colorectal cancer in cell lines, mapping CREs and
      integrating these with whole-genome sequence and expression data from The Cancer
      Genome Atlas7,8. We identify a recurrently mutated CRE interacting with the ETV1
      promoter affecting gene expression. ETV1 expression influences cell viability and
      is associated with patient survival. We further refine our understanding of the
      regulatory effects of copy-number variations, showing that RASL11A is targeted by
      a previously identified enhancer amplification1. This study reveals new insights
      into the complex genetic alterations driving tumor development, providing a
      paradigm for employing chromosome conformation capture to decipher non-coding
      CREs relevant to cancer biology.

PMID- 30224644
TI  - Mutational processes shape the landscape of TP53 mutations in human cancer.
AB  - Unlike most tumor suppressor genes, the most common genetic alterations in tumor
      protein p53 (TP53) are missense mutations1,2. Mutant p53 protein is often
      abundantly expressed in cancers and specific allelic variants exhibit dominant
      negative or gain-of-function activities in experimental models3-8. To gain a
      systematic view of p53 function, we interrogated loss-of-function screens
      conducted in hundreds of human cancer cell lines and performed TP53 saturation
      mutagenesis screens in an isogenic pair of TP53 wild-type and null cell lines. We
      found that loss or dominant-negative inhibition of wild-type p53 function
      reliably enhanced cellular fitness. By integrating these data with the Catalog of
      Somatic Mutations in Cancer (COSMIC) mutational signatures database9,10, we
      developed a statistical model that describes the TP53 mutational spectrum as a
      function of the baseline probability of acquiring each mutation and the fitness
      advantage conferred by attenuation of p53 activity. Collectively, these
      observations show that widely-acting and tissue-specific mutational processes
      combine with phenotypic selection to dictate the frequencies of recurrent TP53
      mutations.

PMID- 30224645
TI  - Genomic history of the Sardinian population.
AB  - The population of the Mediterranean island of Sardinia has made important
      contributions to genome-wide association studies of complex disease traits and,
      based on ancient DNA studies of mainland Europe, Sardinia is hypothesized to be a
      unique refuge for early Neolithic ancestry. To provide new insights on the
      genetic history of this flagship population, we analyzed 3,514 whole-genome
      sequenced individuals from Sardinia. Sardinian samples show elevated levels of
      shared ancestry with Basque individuals, especially samples from the more
      historically isolated regions of Sardinia. Our analysis also uniquely illuminates
      how levels of genetic similarity with mainland ancient DNA samples varies subtly
      across the island. Together, our results indicate that within-island substructure
      and sex-biased processes have substantially impacted the genetic history of
      Sardinia. These results give new insight into the demography of ancestral
      Sardinians and help further the understanding of sharing of disease risk alleles
      between Sardinia and mainland populations.

PMID- 30224646
TI  - Functional classification of long non-coding RNAs by k-mer content.
AB  - The functions of most long non-coding RNAs (lncRNAs) are unknown. In contrast to
      proteins, lncRNAs with similar functions often lack linear sequence homology;
      thus, the identification of function in one lncRNA rarely informs the
      identification of function in others. We developed a sequence comparison method
      to deconstruct linear sequence relationships in lncRNAs and evaluate similarity
      based on the abundance of short motifs called k-mers. We found that lncRNAs of
      related function often had similar k-mer profiles despite lacking linear
      homology, and that k-mer profiles correlated with protein binding to lncRNAs and
      with their subcellular localization. Using a novel assay to quantify Xist-like
      regulatory potential, we directly demonstrated that evolutionarily unrelated
      lncRNAs can encode similar function through different spatial arrangements of
      related sequence motifs. K-mer-based classification is a powerful approach to
      detect recurrent relationships between sequence and function in lncRNAs.

PMID- 30224647
TI  - De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone
      H4 lysine 16 acetylation.
AB  - The etiological spectrum of ultra-rare developmental disorders remains to be
      fully defined. Chromatin regulatory mechanisms maintain cellular identity and
      function, where misregulation may lead to developmental defects. Here, we report
      pathogenic variations in MSL3, which encodes a member of the chromatin-associated
      male-specific lethal (MSL) complex responsible for bulk histone H4 lysine 16
      acetylation (H4K16ac) in flies and mammals. These variants cause an X-linked
      syndrome affecting both sexes. Clinical features of the syndrome include global
      developmental delay, progressive gait disturbance, and recognizable facial
      dysmorphism. MSL3 mutations affect MSL complex assembly and activity, accompanied
      by a pronounced loss of H4K16ac levels in vivo. Patient-derived cells display
      global transcriptome alterations of pathways involved in morphogenesis and cell
      migration. Finally, we use histone deacetylase inhibitors to rebalance
      acetylation levels, alleviating some of the molecular and cellular phenotypes of
      patient cells. Taken together, we characterize a syndrome that allowed us to
      decipher the developmental importance of MSL3 in humans.

PMID- 30224648
TI  - Reply to 'Mutations in RECQL are not associated with breast cancer risk in an
      Australian population'.

PMID- 30224649
TI  - Fine-mapping and functional studies highlight potential causal variants for
      rheumatoid arthritis and type 1 diabetes.
AB  - To define potentially causal variants for autoimmune disease, we fine-mapped1,2
      76 rheumatoid arthritis (11,475 cases, 15,870 controls)3 and type 1 diabetes loci
      (9,334 cases, 11,111 controls)4. After sequencing 799 1-kilobase regulatory
      (H3K4me3) regions within these loci in 568 individuals, we observed accurate
      imputation for 89% of common variants. We defined credible sets of <=5 causal
      variants at 5 rheumatoid arthritis and 10 type 1 diabetes loci. We identified
      potentially causal missense variants at DNASE1L3, PTPN22, SH2B3, and TYK2, and
      noncoding variants at MEG3, CD28-CTLA4, and IL2RA. We also identified potential
      candidate causal variants at SIRPG and TNFAIP3. Using functional assays, we
      confirmed allele-specific protein binding and differential enhancer activity for
      three variants: the CD28-CTLA4 rs117701653 SNP, MEG3 rs34552516 indel, and
      TNFAIP3 rs35926684 indel.

PMID- 30224650
TI  - Promoter bivalency favors an open chromatin architecture in embryonic stem cells.
AB  - In embryonic stem cells (ESCs), developmental gene promoters are characterized by
      their bivalent chromatin state, with simultaneous modification by MLL2 and
      Polycomb complexes. Although essential for embryogenesis, bivalency is
      functionally not well understood. Here, we show that MLL2 plays a central role in
      ESC genome organization. We generate a catalog of bona fide bivalent genes in
      ESCs and demonstrate that loss of MLL2 leads to increased Polycomb occupancy.
      Consequently, promoters lose accessibility, long-range interactions are
      redistributed, and ESCs fail to differentiate. We pose that bivalency balances
      accessibility and long-range connectivity of promoters, allowing developmental
      gene expression to be properly modulated.

PMID- 30224651
TI  - Mutations in RECQL are not associated with breast cancer risk in an Australian
      population.

PMID- 30224652
TI  - Publisher Correction: The sea lamprey germline genome provides insights into
      programmed genome rearrangement and vertebrate evolution.
AB  - When published, this article did not initially appear open access. This error has
      been corrected, and the open access status of the paper is noted in all versions
      of the paper. Additionally, affiliation 16 denoting equal contribution was
      missing from author Robb Krumlauf in the PDF originally published. This error has
      also been corrected.

PMID- 30224654
TI  - A zeolitic vanadotungstate family with structural diversity and ultrahigh
      porosity for catalysis.
AB  - Design of the structure and composition of crystalline microporous inorganic
      oxides is of great importance in catalysis. Developing new zeolites is one
      approach towards this design because of the tunable pore system and high thermal
      stability. Zeolites are limited to main group elements, which limits their
      applications in redox catalysis. Another promising choice is zeolitic transition
      metal oxides providing both porosity and redox activity, thereby further
      expanding the diversity of porous materials. However, the examples of zeolitic
      transition metal oxides are rare. Here, we report a new class of zeolitic
      vanadotungstates with tunable frameworks exhibiting a large porosity and redox
      activity. The assembly of [W4O16]8- units with VO2+ forms two isomeric porous
      frameworks. Owing to the complex redox properties and open porosity, the
      vanadotungstates efficiently catalyse the selective reduction of NO by NH3. This
      finding provides an opportunity for design and synthesis of inorganic
      multifunctional materials for future catalytic applications.

PMID- 30224655
TI  - A key function for microtubule-associated-protein 6 in activity-dependent
      stabilisation of actin filaments in dendritic spines.
AB  - Emerging evidence indicates that microtubule-associated proteins (MAPs) are
      implicated in synaptic function; in particular, mice deficient for MAP6 exhibit
      striking deficits in plasticity and cognition. How MAP6 connects to plasticity
      mechanisms is unclear. Here, we address the possible role of this protein in
      dendritic spines. We find that in MAP6-deficient cortical and hippocampal
      neurons, maintenance of mature spines is impaired, and can be restored by
      expressing a stretch of the MAP6 sequence called Mc modules. Mc modules directly
      bind actin filaments and mediate activity-dependent stabilisation of F-actin in
      dendritic spines, a key event of synaptic plasticity. In vitro, Mc modules
      enhance actin filament nucleation and promote the formation of stable, highly
      ordered filament bundles. Activity-induced phosphorylation of MAP6 likely
      controls its transfer to the spine cytoskeleton. These results provide a
      molecular explanation for the role of MAP6 in cognition, enlightening the
      connection between cytoskeletal dysfunction, synaptic impairment and
      neuropsychiatric illnesses.

PMID- 30224656
TI  - Hotspots of soil organic carbon storage revealed by laboratory hyperspectral
      imaging.
AB  - Subsoil organic carbon (OC) is generally lower in content and more heterogeneous
      than topsoil OC, rendering it difficult to detect significant differences in
      subsoil OC storage. We tested the application of laboratory hyperspectral imaging
      with a variety of machine learning approaches to predict OC distribution in
      undisturbed soil cores. Using a bias-corrected random forest we were able to
      reproduce the OC distribution in the soil cores with very good to excellent model
      goodness-of-fit, enabling us to map the spatial distribution of OC in the soil
      cores at very high resolution (~53 * 53 um). Despite a large increase in variance
      and reduction in OC content with increasing depth, the high resolution of the
      images enabled statistically powerful analysis in spatial distribution of OC in
      the soil cores. In contrast to the relatively homogeneous distribution of OC in
      the plough horizon, the subsoil was characterized by distinct regions of OC
      enrichment and depletion, including biopores which contained ~2-10 times higher
      SOC contents than the soil matrix in close proximity. Laboratory hyperspectral
      imaging enables powerful, fine-scale investigations of the vertical distribution
      of soil OC as well as hotspots of OC storage in undisturbed samples, overcoming
      limitations of traditional soil sampling campaigns.

PMID- 30224657
TI  - Ultrawide Bandwidth Electromagnetic Wave Absorbers Composed of Double-Layer
      Frequency Selective Surfaces with Different Patterns.
AB  - A novel design for an ultra-wide bandwidth and thin microwave absorber is
      introduced utilizing two frequency selective surfaces (FSSs) with different
      patterns of resonating frequencies. The circuit parameters, inductance and
      capacitance, of the three types of FSS (square loop, cross, square patch) were
      determined using an equivalent circuit and strip wire conductor model. The square
      loop FSS indicates a low frequency resonance (10 GHz) due to its high inductance
      and capacitance. On the other hand, the square patch of small inductance reveals
      a high resonating frequency (36 GHz). By optimizing the combination of the two
      FSSs, an ultra-wide absorption bandwidth (6.3-40.0 GHz for -10 dB reflection
      loss) was designed with a small total thickness of 5.5 mm, which is close to the
      theoretical limit. The free space measurement result with a test sample prepared
      by the screen printing method was in good agreement with the simulation result
      and verified the validity of the proposed design method. For these periodic array
      structures, however, the grating lobes were observed above the high frequency
      limit, and it needs to be emphasized that the further control of the unit cell
      periodicity is important, particularly for large oblique incidence angles.

PMID- 30224658
TI  - The population genomics of yellowfin tuna (Thunnus albacares) at global
      geographic scale challenges current stock delineation.
AB  - Yellowfin tuna, Thunnus albacares, is one of the most important seafood
      commodities in the world. Despite its great biological and economic importance,
      conflicting evidence arises from classical genetic and tagging studies concerning
      the yellowfin tuna population structure at local and global oceanic scales.
      Access to more powerful and cost effective genetic tools would represent the
      first step towards resolving the population structure of yellowfin tuna across
      its distribution range. Using a panel of 939 neutral Single Nucleotide
      Polymorphisms (SNPs), and the most comprehensive data set of yellowfin samples
      available so far, we found genetic differentiation among the Atlantic, Indian and
      Pacific oceans. The genetic stock structure analysis carried out with 33 outlier
      SNPs, putatively under selection, identified discrete populations within the
      Pacific Ocean and, for the first time, also within the Atlantic Ocean. Stock
      assessment approaches that consider genetic differences at neutral and adaptive
      genomic loci should be routinely implemented to check the status of the yellowfin
      tuna, prevent illegal trade, and develop more sustainable management measures.

PMID- 30224659
TI  - Optimization of cell-laden bioinks for 3D bioprinting and efficient infection
      with influenza A virus.
AB  - Bioprinting is a new technology, which arranges cells with high spatial
      resolution, but its potential to create models for viral infection studies has
      not yet been fully realized. The present study describes the optimization of a
      bioink composition for extrusion printing. The bioinks were biophysically
      characterized by rheological and electron micrographic measurements. Hydrogels
      consisting of alginate, gelatin and Matrigel were used to provide a scaffold for
      a 3D arrangement of human alveolar A549 cells. A blend containing 20% Matrigel
      provided the optimal conditions for spatial distribution and viability of the
      printed cells. Infection of the 3D model with a seasonal influenza A strain
      resulted in widespread distribution of the virus and a clustered infection
      pattern that is also observed in the natural lung but not in two-dimensional (2D)
      cell culture, which demonstrates the advantage of 3D printed constructs over
      conventional culture conditions. The bioink supported viral replication and
      proinflammatory interferon release of the infected cells. We consider our
      strategy to be paradigmatic for the generation of humanized 3D tissue models by
      bioprinting to study infections and develop new antiviral strategies.

PMID- 30224660
TI  - Method for high frequency tracking and sub-nm sample stabilization in single
      molecule fluorescence microscopy.
AB  - While fluorescence microscopes and atomic force microscopes are widely used to
      visualize, track, and manipulate single biomolecules, the resolution of these
      methods is limited by sample drift. To minimize drift, active feedback methods
      have recently been used to stabilize single molecule microscopes on the sub
      nanometer scale. However, these methods require high intensity lasers which
      limits their application in single molecule fluorescence measurements.
      Furthermore, these feedback methods do not track user-defined regions of the
      sample, but rather monitor the relative displacement of an unknown point on a
      fiducial marker, which limits their use in biological force measurements. To
      overcome these limitations, we have developed a novel method to image, track and
      stabilize a sample using low laser intensities. We demonstrate the capabilities
      of our approach by tracking a user-chosen point on a fiducial marker at 8.6 kHz
      and stabilizing it with sub-nanometer resolution. We further showcase the
      application of our method in single molecule fluorescence microscopy by imaging
      and stabilizing individual fluorescently-tagged streptavidin proteins under
      biologically relevant conditions. We anticipate that our method can be easily
      used to improve the resolution of a wide range of single molecule fluorescence
      microscopy and integrated force-fluorescence applications.

PMID- 30224661
TI  - A Golgi UDP-GlcNAc transporter delivers substrates for N-linked glycans and
      sphingolipids.
AB  - Glycosylation requires activated glycosyl donors in the form of nucleotide sugars
      to drive processes such as post-translational protein modifications and
      glycolipid and polysaccharide biosynthesis. Most of these reactions occur in the
      Golgi, requiring cytosolic-derived nucleotide sugars, which need to be actively
      transferred into the Golgi lumen by nucleotide sugar transporters. We identified
      a Golgi-localized nucleotide sugar transporter from Arabidopsis thaliana with
      affinity for UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) and assigned it UDP-GlcNAc
      transporter 1 (UGNT1). Profiles of N-glycopeptides revealed that plants carrying
      the ugnt1 loss-of-function allele are virtually devoid of complex and hybrid N
      glycans. Instead, the N-glycopeptide population from these alleles exhibited high
      mannose structures, representing structures prior to the addition of the first
      GlcNAc in the Golgi. Concomitantly, sphingolipid profiling revealed that the
      biosynthesis of GlcNAc-containing glycosyl inositol phosphorylceramides (GIPCs)
      is also reliant on this transporter. By contrast, plants carrying the loss-of
      function alleles affecting ROCK1, which has been reported to transport UDP-GlcNAc
      and UDP-N-acetylgalactosamine, exhibit no changes in N-glycan or GIPC profiles.
      Our findings reveal that plants contain a single UDP-GlcNAc transporter that
      delivers an essential substrate for the maturation of N-glycans and the GIPC
      class of sphingolipids.

PMID- 30224653
TI  - Genetic analysis of over 1 million people identifies 535 new loci associated with
      blood pressure traits.
AB  - High blood pressure is a highly heritable and modifiable risk factor for
      cardiovascular disease. We report the largest genetic association study of blood
      pressure traits (systolic, diastolic and pulse pressure) to date in over 1
      million people of European ancestry. We identify 535 novel blood pressure loci
      that not only offer new biological insights into blood pressure regulation but
      also highlight shared genetic architecture between blood pressure and lifestyle
      exposures. Our findings identify new biological pathways for blood pressure
      regulation with potential for improved cardiovascular disease prevention in the
      future.

PMID- 30224662
TI  - FRIGIDA establishes a local chromosomal environment for FLOWERING LOCUS C mRNA
      production.
AB  - FRIGIDA (FRI) upregulates the expression of the potent floral repressor FLOWERING
      LOCUS C (FLC) to confer the winter-annual growth habit in Arabidopsis thaliana:
      accelerated transition to flowering after prolonged cold exposure
      (vernalization). Here, we show that FRI, histone acetyltransferases, the histone
      methyltransferase COMPASS-like and other chromatin modifiers are part of a FRI
      containing supercomplex enriched in a region around the FLC transcription start
      site (TSS) to promote its expression. Several FRI partners are also enriched in a
      3' region flanking FLC and, together with FRI, they function to increase the
      frequency of physical association of the region around TSS with the 3' region and
      promote the expression of both sense FLC and antisense non-coding RNAs. Our
      results show that the FRI supercomplex establishes a local chromosomal
      environment at FLC with active chromatin modifications and topology to promote
      transcriptional activation, fast elongation and efficient pre-messenger RNA
      splicing, leading to a high-level production of FLC mRNAs.

PMID- 30224663
TI  - A path to a biennial life history.

PMID- 30224664
TI  - Rapid Shifts of Peak Flowering Phenology in 12 Species under the Effects of
      Extreme Climate Events in Macao.
AB  - Plant phenology is sensitive to climate change; the timing of flowering has
      served as a visible indicator of plant phenology in numerous studies. The present
      study used phenological records from a manual monitoring program to characterize
      the flowering phenology of 12 species in Guia Hill, Macao. The mean peak
      flowering dates (PFDs) of these species ranged from March to September, 41.7% of
      which occurred in May. The earliest or latest PFDs of nine species occurred in
      2013, a year with extremely heavy rain events in early spring. In addition, we
      found that, in the 5-year period, the monthly mean temperature or monthly
      precipitation in two periods, specifically 1) during November to December of the
      previous year and 2) during 0-2 months before the PFDs of each species, were
      significantly correlated with the PFD of eight species. The result showed that,
      even though complex species-specific responses to the characteristics of climate
      widely exist, most species in the present study responded to shifts in climate
      shifts in these two periods. In addition, some species were extraordinarily
      sensitive to extreme climate events. Precipitation was more effective in altering
      flowering date than temperature, especially among the late-flowering species in
      Guia Hill, Macao.

PMID- 30224665
TI  - MicroRNAs delivery into human cells grown on 3D-printed PLA scaffolds coated with
      a novel fluorescent PAMAM dendrimer for biomedical applications.
AB  - Many advanced synthetic, natural, degradable or non-degradable materials have
      been employed to create scaffolds for cell culture for biomedical or tissue
      engineering applications. One of the most versatile material is poly-lactide
      (PLA), commonly used as 3D printing filament. Manufacturing of multifunctional
      scaffolds with improved cell growth proliferation and able to deliver
      oligonucleotides represents an innovative strategy for controlled and localized
      gene modulation that hold great promise and could increase the number of
      applications in biomedicine. Here we report for the first time the synthesis of a
      novel Rhodamine derivative of a poly-amidoamine dendrimer (G = 5) able to
      transfect cells and to be monitored by confocal microscopy that we also employed
      to coat a 3D-printed PLA scaffold. The coating do not modify the oligonucleotide
      binding ability, toxicity or transfection properties of the scaffold that is able
      to increase cell proliferation and deliver miRNA mimics (i.e., pre-mir-503) into
      human cells. Although further experiments are required to optimize the
      dendrimer/miRNA ratio and improve transfection efficiency, we demonstrated the
      effectiveness of this promising and innovative 3D-printed transfection system to
      transfer miRNAs into human cells for future biomedical applications.

PMID- 30224666
TI  - Accurate Risk Assessment of Patients with Pathologic T3aN0M0 Renal Cell
      Carcinoma.
AB  - To develop a more precise risk-stratification system by investigating the
      prognostic impact of tumor growth within fatty tissues surrounding the kidney
      and/or renal vein. We conducted a retrospective review of the medical records of
      211 patients with a pathologic diagnosis of T3aN0M0RCC among 4,483 renal cell
      carcinoma (RCC) patients from February 1988 to December 2015 according to the
      number of T3a pathologies-extrarenal fat invasion (EFI) and/or renal venous
      invasion (RVI). During a mean follow-up duration of 38.8 months, the patients
      with both pathologies (EFI + RVI) had lower recurrence free survival (RFS) rate
      than those with only a single pathology (p = 0.001). Using multivariable Cox
      regression analysis, the presence of both factors was shown to be an independent
      predictor of RFS (HR = 1.964, p = 0.032); cancer specific survival rate was not
      different among patients with EFI and/or RVI. Patients with pathologic T3aN0M0
      RCC presenting with both EFI and RVI were at an increased risk of recurrence
      following nephrectomy. Therefore, pathologic T3a RCC could be sub-divided into
      those with favorable and unfavorable disease according to presence of EFI and/or
      RVI pathologies.

PMID- 30224667
TI  - MiR-423-5p in brain metastasis: potential role in diagnostics and molecular
      biology.
AB  - During the last several years, a growing number of studies have shown that
      microRNAs (miRNAs) participate in cancer metastasis. Brain metastasis (BM) is a
      frequent complication of lung adenocarcinoma (LAD), and the incidence of locally
      advanced LAD with BM can be as high as 30-50%. This study was performed to
      identify the miRNA expression patterns of LAD with BM and to determine the
      biological role that miRNAs play in tumorigenesis. To this end, we conducted
      microarray and quantitative PCR analyses to evaluate BM-related miRNAs
      independently validated from a total of 155 patients with LAD. A series of in
      vivo and in vitro assays were also conducted to verify the impact of miRNAs on
      BM. We found significantly increased expression of miR-423-5p, and BM was
      predicted in non-small cell lung cancer when compared to LAD without BM. We next
      examined the function of miR-423-5p and discovered that it significantly promoted
      colony formation, cell motility, migration, and invasion in vitro. We
      computationally and experimentally confirmed that metastasis suppressor 1 (MTSS1)
      was a direct miR-423-5p target. Through a combination of image, histological, and
      molecular analyses, we found that miR-423-5p overexpression significantly
      increased tumor burden, local invasion, and distant BM. The level of MTSS1
      expression was inversely correlated with miR-423-5p upregulation in the LAD
      specimens and was associated with survival of patients with BM. MiR-423-5p
      promoted BM in LAD and inhibited MTSS1 expression. Together, these results show
      that MiR-423-5p has the potential to be a marker of BM and/or a therapeutic
      target in LAD.

PMID- 30224668
TI  - Comparison of Significant Carotid Stenosis for Nasopharyngeal Carcinoma between
      Intensity-Modulated Radiotherapy and Conventional Two-Dimensional Radiotherapy.
AB  - Radiotherapy (RT) serves as the most efficient treatment for nasopharyngeal
      carcinoma (NPC) and can cause carotid stenosis. This work compared the incidence
      of significant carotid stenosis between intensity-modulated radiotherapy (IMRT)
      and two-dimensional conventional radiotherapy (2D-RT) for NPC and explored the
      risk factors. We retrospectively reviewed 233 cases with NPC who underwent
      carotid ultrasound post IMRT or 2D-RT from 2006 to 2015. The incidence of
      significant stenosis after RT was 19.3%. Significant stenosis was identified in
      20 (14.6%) of 137 patients treated with IMRT and 25 (26.0%) of 96 patients with
      2D-RT, respectively (p = 0.035). Multivariate logistic analysis indicated age
      (odds ratio = 1.054, 95% CI = 1.011-1.099, p = 0.014), radiation technique (IMRT)
      (odds ratio = 0.471, 95%CI = 0.241-0.919, p = 0.027) and time interval (odds
      ratio = 1.068, 95%CI = 1.033-1.105, p = 0.001) as independent predictors for
      significant carotid stenosis. Our study suggests that IMRT was associated with
      decreased incidence of significant carotid stenosis versus 2D-RT for NPC.
      Prevention and carotid ultrasound should be considered for older NPC survivors
      with longer interval from RT, especially those treated with 2D-RT.

PMID- 30224669
TI  - Three-dimensional X-ray diffraction imaging of dislocations in polycrystalline
      metals under tensile loading.
AB  - The nucleation and propagation of dislocations is an ubiquitous process that
      accompanies the plastic deformation of materials. Consequently, following the
      first visualization of dislocations over 50 years ago with the advent of the
      first transmission electron microscopes, significant effort has been invested in
      tailoring material response through defect engineering and control. To accomplish
      this more effectively, the ability to identify and characterize defect structure
      and strain following external stimulus is vital. Here, using X-ray Bragg coherent
      diffraction imaging, we describe the first direct 3D X-ray imaging of the strain
      field surrounding a line defect within a grain of free-standing nanocrystalline
      material following tensile loading. By integrating the observed 3D structure into
      an atomistic model, we show that the measured strain field corresponds to a screw
      dislocation.

PMID- 30224670
TI  - A(TR) checkpoint for S/G2 transition.

PMID- 30224671
TI  - Template-free 2D particle fusion in localization microscopy.
AB  - Methods that fuse multiple localization microscopy images of a single structure
      can improve signal-to-noise ratio and resolution, but they generally suffer from
      template bias or sensitivity to registration errors. We present a template-free
      particle-fusion approach based on an all-to-all registration that provides
      robustness against individual misregistrations and underlabeling. We achieved 3.3
      nm Fourier ring correlation (FRC) image resolution by fusing 383 DNA origami
      nanostructures with 80% labeling density, and 5.0-nm resolution for structures
      with 30% labeling density.

PMID- 30224672
TI  - Label-free prediction of three-dimensional fluorescence images from transmitted
      light microscopy.
AB  - Understanding cells as integrated systems is central to modern biology. Although
      fluorescence microscopy can resolve subcellular structure in living cells, it is
      expensive, is slow, and can damage cells. We present a label-free method for
      predicting three-dimensional fluorescence directly from transmitted-light images
      and demonstrate that it can be used to generate multi-structure, integrated
      images. The method can also predict immunofluorescence (IF) from electron
      micrograph (EM) inputs, extending the potential applications.

PMID- 30224673
TI  - Inferring single-trial neural population dynamics using sequential auto-encoders.
AB  - Neuroscience is experiencing a revolution in which simultaneous recording of
      thousands of neurons is revealing population dynamics that are not apparent from
      single-neuron responses. This structure is typically extracted from data averaged
      across many trials, but deeper understanding requires studying phenomena detected
      in single trials, which is challenging due to incomplete sampling of the neural
      population, trial-to-trial variability, and fluctuations in action potential
      timing. We introduce latent factor analysis via dynamical systems, a deep
      learning method to infer latent dynamics from single-trial neural spiking data.
      When applied to a variety of macaque and human motor cortical datasets, latent
      factor analysis via dynamical systems accurately predicts observed behavioral
      variables, extracts precise firing rate estimates of neural dynamics on single
      trials, infers perturbations to those dynamics that correlate with behavioral
      choices, and combines data from non-overlapping recording sessions spanning
      months to improve inference of underlying dynamics.

PMID- 30224674
TI  - A new Eocene anagalid (Mammalia: Euarchontoglires) from Mongolia and its
      implications for the group's phylogeny and dispersal.
AB  - Anagalidae are extinct primitive Euarchontoglires from Asia, regarded as
      relatively closely related to basal Glires. So far, the group has been reported
      only from China and stratigraphically spans from the early Paleocene to the
      latest Eocene/earliest Oligocene. Anagalids are characterized by a relatively
      full dental formula featuring slightly enlarged semi-procumbent incisors,
      prominent canines, and tall cheek teeth with usually heavily worn crowns,
      indicative of an abrasive diet. Here we report a new genus and species from the
      late Eocene Ergilin Dzo Formation in southern Mongolia. The first non-Chinese
      anagalid is also the northernmost record of the family. Zofiagale ergilinensis
      gen. and sp.nov. is remarkable for its relatively small size (comparable only to
      the Paleocene genera Huaiyangale and Stenanagale), lack of P1, and molariform
      teeth showing almost no wear, suggesting a different diet than most Anagalidae.
      Furthermore, its molars display a strong buccal cingulum, a character in
      anagalids shared only with Wanogale. Our phylogenetic analysis of representatives
      of all anagalid genera based on 82 dental characters places Anagale and
      Anaptogale as the most basal lineages and clusters Zofiagale gen. nov. together
      with Qipania and Hsiuannania. These results suggest three independent northward
      dispersal events within the family in the late Eocene.

PMID- 30224675
TI  - Dominance of cropland reduces the pollen deposition from bumble bees.
AB  - Intensive agricultural landscapes can be hostile for bees due to a lack of floral
      and nesting resources, and due to management-related stress such as pesticide use
      and soil tillage. This threatens the pollination services that bees deliver to
      insect-pollinated crops. We studied the effects of farming intensity (organic vs.
      conventional, number of insecticide applications) and availability of semi
      natural habitats at the field and landscape scale on pollinator visits and pollen
      delivery to pumpkin in Germany. We found that wild bumble bees were the key
      pollinators of pumpkin in terms of pollen delivery, despite fivefold higher
      visitation frequency of honey bees. Critically, we observed that the area of
      cropland had stronger effects on bees' pollen deposition than the area of
      seminatural habitats. Specifically, a 10% increase of the proportion of cropland
      reduced pollen delivery by 7%. Pumpkin provides a striking example for a key role
      of wild pollinators in crop pollination even at high numerical dominance of honey
      bees. In addition, our findings suggest that habitat conversion to agricultural
      land is a driver of deteriorating pollination. This underlines the importance to
      maintain sufficient areas of non-crop habitats in agricultural landscapes.

PMID- 30224676
TI  - Neural Signatures of the Configural Superiority Effect and Fundamental Emergent
      Features in Human Vision.
AB  - The concepts of grouping, emergence, and superadditivity (when a whole is
      qualitatively different from the sum of its parts) are critical in Gestalt
      psychology and essential to properly understand the information processing
      mechanisms underlying visual perception. However, very little is known about the
      neural processes behind these phenomena (particularly in terms of their
      generality vs. specificity and their time-course). Here, we used the configural
      superiority effect as a way to define "emergence" and "emergent features"
      operationally, employing an approach that can isolate different emergent features
      and compare them on a common scale. By assessing well-established event related
      potentials in a HD-EEG system, we found that the critical processes behind
      configural superiority and superadditive Gestalt phenomena are present in the
      window between 100 and 200 ms after stimulus onset and that these effects seem to
      be driven by specific attentional selection mechanisms. Also, some emergent
      features seem to be differentially processed in different brain hemispheres.
      These results shed new light on the issues of the generality vs. specificity of
      the neural correlates of different Gestalt principles, the hemispheric
      asymmetries in the processing of hierarchical image structure and the role of the
      N1 ERP component in reflecting feature selective mechanisms.

PMID- 30224677
TI  - Epitopes identified in GAPDH from Clostridium difficile recognized as common
      antigens with potential autoimmunizing properties.
AB  - Clostridium difficile (CD) infections are a growing threat due to the strain
      resistance to antibiotic treatment and the emergence of hypervirulent strains.
      One solution to this problem is the search for new vaccine antigens, preferably
      surface-localized that will be recognized by antibodies at an early stage of
      colonization. The purpose of the study was to assess the usefulness of novel
      immunoreactive surface proteins (epitopes) as potential vaccine antigens. Such
      approach might be tough to pursue since pathogens have acquired strategies to
      subvert adaptive immune response to produce humoral response against non
      essential proteins for their survival. In this study CD surface proteins were
      isolated, immunoreactive proteins identified and mapped to select potential
      epitopes. The results of the study exclude the use of CD glyceraldehyde 3
      phosphate dehydrogenase as a vaccine antigen, especially as a whole protein.
      Sequences P9 (201AAGNIVPNTTGAAKAI218) and P10 (224KGKLDGAAQRVPVVTG241) recognized
      by patients sera are conserved and widespread among CD strains. They show cross
      reactivity with sera of people suffering from other bacterial infections and are
      recognized by sera of autoimmune disease patients. Our study documents that
      special care in analyzing the sequence of new epitope should be taken to avoid
      side effects prior to consider it as a vaccine antigen.

PMID- 30224678
TI  - The multi-level and multi-dimensional quantum wavelet packet transforms.
AB  - The classical wavelet packet transform has been widely applied in the information
      processing field. It implies that the quantum wavelet packet transform (QWPT) can
      play an important role in quantum information processing. In this paper, we
      design quantum circuits of a generalized tensor product (GTP) and a perfect
      shuffle permutation (PSP). Next, we propose multi-level and multi-dimensional
      (1D, 2D and 3D) QWPTs, including a Haar QWPT (HQWPT), a D4 QWPT (DQWPT) based on
      the periodization extension and their inverse transforms for the first time, and
      prove the correctness based on the GTP and PSP. Furthermore, we analyze the
      quantum costs and the time complexities of our proposed QWPTs and obtain precise
      results. The time complexities of HQWPTs is at most 6 on 2n elements, which
      illustrates high-efficiency of the proposed QWPTs. Simulation experiments
      demonstrate that the proposed QWPTs are correct and effective.

PMID- 30224679
TI  - High niche diversity in Mesozoic pollinating lacewings.
AB  - Niche diversity of pollinating insects plays a vital role in maintaining extant
      terrestrial ecosystems. A key dimension of pollination niches refers to the
      insect proboscis length that commonly matches the floral tube length. Here we
      describe new kalligrammatid lacewings (an iconic Mesozoic pollinating insect
      lineage) from late Cretaceous Burmese amber and Mesozoic sediments in China.
      Kalligrammatids display complex configurations of elongate mouthpart elements
      consisting of well-developed maxillae, labium and their palps. The mouthpart
      lengths vary among species, from 0.6 to 18.0 mm, suggesting corresponding
      variability in the floral tube lengths of Mesozoic plants. With the
      diversification of pollinating habits, the kalligrammatids presented highly
      divergent traits related to chemical communication and defence mechanisms.
      Together with other Mesozoic long-proboscid insects, these fossils not only
      reveal the high niche diversity of Mesozoic pollinating insects but also
      highlight the diversity of Mesozoic pollinator-dependent plants prior to the rise
      of angiosperms.

PMID- 30224680
TI  - Large diurnal bottom temperature oscillations around the Saint Pierre and
      Miquelon archipelago.
AB  - Here, we report large, near-daily oscillations of near-bottom temperatures, with
      ranges of up to 11.5  degrees C at depths of 30-60 m in September 2011 around the
      Saint Pierre and Miquelon archipelago (south-eastern Canada). These oscillations
      were detected on velocity and temperature profiles from moorings in Miquelon Bay
      and on an array of near-bottom temperature sensors around the archipelago. The
      oscillations coincided with the seasonal stratification period. In addition to
      their remarkable range, they exhibited a near-diurnal period centred on the O1
      tidal component (~26 h), contrasting with the dominant semi-diurnal sea-level
      periodicity in the area. They appear to be the manifestation of an internal wave,
      triggered by the diurnal surface tide and trapped by the bathymetric
      configuration of the area. We argue that the archipelago is nearly resonant for
      island-trapped waves at near-diurnal frequencies. Our data demonstrate that these
      coastal-trapped waves propagate clockwise around the archipelago in roughly two
      days, and thus approximate an azimuthal, mode 2 pattern. Simplified calculations
      show that cross-shore motions are bottom-amplified. In addition, bottom friction
      acts to rotate the axes of the diurnal tidal current ellipses with depth, and
      this combination of effects explains the large range of observed bottom
      temperature oscillations.

PMID- 30224681
TI  - Development of a novel Hsp90 inhibitor NCT-50 as a potential anticancer agent for
      the treatment of non-small cell lung cancer.
AB  - Despite the development of advanced therapeutic regimens such as molecular
      targeted therapy and immunotherapy, the 5-year survival of patients with lung
      cancer is still less than 20%, suggesting the need to develop additional
      treatment strategies. The molecular chaperone heat shock protein 90 (Hsp90) plays
      important roles in the maturation of oncogenic proteins and thus has been
      considered as an anticancer therapeutic target. Here we show the efficacy and
      biological mechanism of a Hsp90 inhibitor NCT-50, a novobiocin-deguelin analog
      hybridizing the pharmacophores of these known Hsp90 inhibitors. NCT-50 exhibited
      significant inhibitory effects on the viability and colony formation of non-small
      cell lung cancer (NSCLC) cells and those carrying resistance to chemotherapy. In
      contrast, NCT-50 showed minimal effects on the viability of normal cells. NCT-50
      induced apoptosis in NSCLC cells, inhibited the expression and activity of
      several Hsp90 clients including hypoxia-inducible factor (HIF)-1alpha, and
      suppressed pro-angiogenic effects of NSCLC cells. Further biochemical and in
      silico studies revealed that NCT-50 downregulated Hsp90 function by interacting
      with the C-terminal ATP-binding pocket of Hsp90, leading to decrease in the
      interaction with Hsp90 client proteins. These results suggest the potential of
      NCT-50 as an anticancer Hsp90 inhibitor.

PMID- 30224682
TI  - Rotavirus-Induced Early Activation of the RhoA/ROCK/MLC Signaling Pathway
      Mediates the Disruption of Tight Junctions in Polarized MDCK Cells.
AB  - Intestinal epithelial tight junctions (TJ) are a major barrier restricting the
      entry of various harmful factors including pathogens; however, they also
      represent an important entry portal for pathogens. Although the rotavirus-induced
      early disruption of TJ integrity and targeting of TJ proteins as coreceptors are
      well-defined, the precise molecular mechanisms involved remain unknown. In the
      present study, infection of polarized MDCK cells with the species A rotavirus
      (RVA) strains human DS-1 and bovine NCDV induced a redistribution of TJ proteins
      into the cytoplasm, a reversible decrease in transepithelial resistance, and an
      increase in paracellular permeability. RhoA/ROCK/MLC signaling was identified as
      activated at an early stage of infection, while inhibition of this pathway
      prevented the rotavirus-induced early disruption of TJ integrity and alteration
      of TJ protein distribution. Activation of pMYPT, PKC, or MLCK, which are known to
      participate in TJ dissociation, was not observed in MDCK cells infected with
      either rotavirus strain. Our data demonstrated that binding of RVA virions or
      cogent VP8* proteins to cellular receptors activates RhoA/ROCK/MLC signaling,
      which alters TJ protein distribution and disrupts TJ integrity via contraction of
      the perijunctional actomyosin ring, facilitating virion access to coreceptors and
      entry into cells.

PMID- 30224683
TI  - Assembly of Plasmonic and Magnetic Nanoparticles with Fluorescent Silica Shell
      Layer for Tri-functional SERS-Magnetic-Fluorescence Probes and Its
      Bioapplications.
AB  - In this study, we report on the fabrication of multilayered tri-functional
      magnetic-SERS-fluorescence nanoprobes (MF-SERS particles) containing clustered
      superparamagnetic Fe3O4 nanoparticles (NPs), silver NPs, and a fluorescent silica
      layer. The MF-SERS particles exhibited strong SERS signals from the silver NPs as
      well as both superparamagnetism and fluorescence. MF-SERS particles were uptaken
      by cells, allowing successful separation using an external magnetic field. SERS
      and fluorescence signals could be detected from the NP-containing cells, and CD44
      antibody-conjugated MF-SERS particles selectively targeted MDA-MB-231 cells.
      Based on these properties, MF-SERS particles proved to be a useful nanoprobe for
      multiplex detection and separation of cancer cells.

PMID- 30224684
TI  - Spontaneous doping of the basal plane of MoS2 single layers through oxygen
      substitution under ambient conditions.
AB  - The chemical inertness of the defect-free basal plane confers environmental
      stability to MoS2 single layers, but it also limits their chemical versatility
      and catalytic activity. The stability of pristine MoS2 basal plane against
      oxidation under ambient conditions is a widely accepted assumption however, here
      we report single-atom-level structural investigations that reveal that oxygen
      atoms spontaneously incorporate into the basal plane of MoS2 single layers during
      ambient exposure. The use of scanning tunnelling microscopy reveals a slow oxygen
      substitution reaction, during which individual sulfur atoms are replaced one by
      one by oxygen, giving rise to solid-solution-type 2D MoS2-xOx crystals. Oxygen
      substitution sites present all over the basal plane act as single-atom reaction
      centres, substantially increasing the catalytic activity of the entire MoS2 basal
      plane for the electrochemical H2 evolution reaction.

PMID- 30224685
TI  - Carbohydrate stabilization extends the kinetic limits of chemical polysaccharide
      depolymerization.
AB  - Polysaccharide depolymerization is an essential step for valorizing
      lignocellulosic biomass. In inexpensive systems such as pure water or dilute acid
      mixtures, carbohydrate monomer degradation rates exceed hemicellulose-and
      especially cellulose-depolymerization rates at most easily accessible
      temperatures, limiting sugar yields. Here, we use a reversible stabilization of
      xylose and glucose by acetal formation with formaldehyde to alter this kinetic
      paradigm, preventing sugar dehydration to furans and their subsequent
      degradation. During a harsh organosolv pretreatment in the presence of
      formaldehyde, over 90% of xylan in beech wood was recovered as diformylxylose
      (compared to 16% xylose recovery without formaldehyde). The subsequent
      depolymerization of cellulose led to carbohydrate yields over 70% and a final
      concentration of ~5 wt%, whereas the same conditions without formaldehyde gave a
      yield of 28%. This stabilization strategy pushes back the longstanding kinetic
      limits of polysaccharide depolymerization and enables the recovery of biomass
      derived carbohydrates in high yields and concentrations.

PMID- 30224687
TI  - PUP up the volume.

PMID- 30224686
TI  - Thiophene and its sulfur inhibit indenoindenodibenzothiophene diradicals from low
      energy lying thermal triplets.
AB  - Many qualitative structure-property correlations between diradical character and
      emerging molecular properties are known. For example, the increase of diradical
      character further decreases the singlet-triplet energy gap. Here we show that
      inclusion of thiophenes within a quinoidal polycyclic hydrocarbon imparts
      appreciable diradical character yet retains the large singlet-triplet energy gap,
      a phenomenon that has no precedent in the literature. The low aromatic character
      of thiophene and its electron-rich nature are the key properties leading to these
      unique findings. A new indenoindenodibenzothiophene scaffold has been prepared
      and fully characterized by several spectroscopies, magnetic measurements, solid
      state X-ray and state-of-the-art quantum chemical calculations, all corroborating
      this unique dichotomy between the diradical input and the emerging magnetic
      properties. New structure-property relationships such as these are not only
      extremely important in the field of diradical chemistry and organic electronics,
      but also provide new insights into the versatility of pi-electron chemical
      bonding.

PMID- 30224688
TI  - Cost-benefit analysis.

PMID- 30224689
TI  - Fatal chemoattraction.

PMID- 30224690
TI  - Diversifying bases.

PMID- 30224691
TI  - A new target for thalidomide.

PMID- 30224692
TI  - The substrate lends a hand.

PMID- 30224693
TI  - Flipping out the peptide.

PMID- 30224694
TI  - Post-translational site-selective protein backbone alpha-deuteration.
AB  - Isotopic replacement has long-proven applications in small molecules. However,
      applications in proteins are largely limited to biosynthetic strategies or
      exchangeable (for example, N-H/D) labile sites only. The development of
      postbiosynthetic, C-1H -> C-2H/D replacement in proteins could enable probing of
      mechanisms, among other uses. Here we describe a chemical method for selective
      protein alpha-carbon deuteration (proceeding from Cys to dehydroalanine (Dha) to
      deutero-Cys) allowing overall 1H->2H/D exchange at a nonexchangeable backbone
      site. It is used here to probe mechanisms of reactions used in protein
      bioconjugation. This analysis suggests, together with quantum mechanical
      calculations, stepwise deprotonations via on-protein carbanions and unexpected
      sulfonium ylides in the conversion of Cys to Dha, consistent with a 'carba-Swern'
      mechanism. The ready application on existing, intact protein constructs (without
      specialized culture or genetic methods) suggests this C-D labeling strategy as a
      possible tool in protein mechanism, structure, biotechnology and medicine.

PMID- 30224695
TI  - T cell receptor cross-reactivity expanded by dramatic peptide-MHC adaptability.
AB  - T cell receptor cross-reactivity allows a fixed T cell repertoire to respond to a
      much larger universe of potential antigens. Recent work has emphasized the
      importance of peptide structural and chemical homology, as opposed to sequence
      similarity, in T cell receptor cross-reactivity. Surprisingly, though, T cell
      receptors can also cross-react between ligands with little physiochemical
      commonalities. Studying the clinically relevant receptor DMF5, we demonstrate
      that cross-recognition of such divergent antigens can occur through mechanisms
      that involve heretofore unanticipated rearrangements in the peptide and
      presenting MHC protein, including binding-induced peptide register shifts and
      extensions from MHC peptide binding grooves. Moreover, cross-reactivity can
      proceed even when such dramatic rearrangements do not translate into structural
      or chemical molecular mimicry. Beyond demonstrating new principles of T cell
      receptor cross-reactivity, our results have implications for efforts to predict
      and control T cell specificity and cross-reactivity and highlight challenges
      associated with predicting T cell reactivities.

PMID- 30224696
TI  - Polyoxometalate-based microcrystal arrays patterned on air-grid superwettable
      surface.
AB  - Surface patterning of polyoxometalates (POMs) is an important step to gain
      functional materials and devices. However, some special requirements such as
      complex operation steps or strict synthesis environment greatly limit their
      further applications. Herein, we have employed a simple and universal strategy
      for patterning POM-based microcrystal arrays on air-grid superwettable surfaces.
      The size and distribution of POM crystals were precisely adjusted by varying the
      pillar parameter of superwettable surface and concentration of POM mother liquid.
      We envision that this POM patterning method may bring valuable insights for
      designing POM-based functional materials and devices.

PMID- 30224697
TI  - Chaperonin 60 sustains osteoblast autophagy and counteracts glucocorticoid
      aggravation of osteoporosis by chaperoning RPTOR.
AB  - Glucocorticoid excess medication interrupts osteoblast homeostasis and
      exacerbates bone mass and microstructure loss ramping up the pathogenesis of
      osteoporotic disorders. Heat shock protein 60 (HSP60) is found to maintain
      protein function within cellular microenvironment upon encountering detrimental
      stress. In this study, we revealed that supraphysiological dexamethasone
      decreased HSP60 expression along with deregulated autophagy in osteoblasts
      cultures. This chaperonin is required to sustain autophagic markers Atg4, and
      Atg12 expression, LC3-II conversion, and autophagic puncta formation, and
      alleviated the glucocorticoid-induced loss of osteogenic gene expression and
      mineralized matrix accumulation. Regulator-associated protein of mTOR complex 1
      (RPTOR) existed in HSP60 immunoprecipitate contributing to the HSP60-promoted
      autophagy and osteogenesis because knocking down RPTOR impaired autophagic influx
      and osteogenic activity. HSP60 shielded from RPTOR dysfunction by reducing the
      glucocorticoid-induced RPTOR de-phosphorylation, aggregation, and ubiquitination.
      In vivo, forced RPTOR expression attenuated the methylprednisolone-induced loss
      of osteoblast autophagy, bone mass, and trabecular microstructure in mice. HSP60
      transgenic mice displayed increased cortical bone, mineral acquisition, and
      osteoblast proliferation along with higher osteogenesis of bone marrow
      mesenchymal cells than those of wild-type mice. HSP60 overexpression retained
      RPTOR signaling, sustained osteoblast autophagy, and compromised the severity of
      glucocorticoid-induced bone loss and sparse trabecular histopathology. Taken
      together, HSP60 is essential to maintain osteoblast autophagy, which facilitates
      mineralized matrix production. It fends off glucocorticoid-induced osteoblast
      apoptosis and bone loss by stabilizing RPTOR action to autophagy. This study
      offers a new insight into the mechanistic by which chaperonin protects against
      the glucocorticoid-induced osteoblast dysfunction and bone loss.

PMID- 30224698
TI  - The shape of watersheds.
AB  - Since the 1950s river networks have been intensely researched in geosciences and
      hydrology. This led to the definition of scaling laws that described the
      organisation of landscapes under fluvial incision and were later explored by
      statistical physics and fractal mathematics. The emblematic Hack's Law proposes a
      power-law relationship between watershed area and main stream length. Though
      extensively documented, a wide range of values is still reported for Hack's
      parameters. Some authors associate this dispersion to local geologic and climatic
      conditions. Here based on the analysis of large sets of river basins in various
      climatic and geological settings, we confirm the geometric similarity of river
      networks. We demonstrate that basin shape is mostly related to Hack's coefficient
      and not to the exponent, independently of external forcing such as lithology and
      pluviometry.

PMID- 30224699
TI  - Propofol inhibits parthanatos via ROS-ER-calcium-mitochondria signal pathway in
      vivo and vitro.
AB  - Parthanatos is a new form of programmed cell death. It has been recognized to be
      critical in cerebral ischemia-reperfusion injury, and reactive oxygen species
      (ROS) can induce parthanatos. Recent studies found that propofol, a widely used
      intravenous anesthetic agent, has an inhibitory effect on ROS and has
      neuroprotective in many neurological diseases. However, the functional roles and
      mechanisms of propofol in parthanatos remain unclear. Here, we discovered that
      the ROS-ER-calcium-mitochondria signal pathway mediated parthanatos and the
      significance of propofol in parthanatos. Next, we found that ROS overproduction
      would cause endoplasmic reticulum (ER) calcium release, leading to mitochondria
      depolarization with the loss of mitochondrial membrane potential. Mitochondria
      depolarization caused mitochondria to release more ROS, which, in turn,
      contributed to parthanatos. Also, we found that propofol inhibited parthanatos
      through impeding ROS overproduction, calcium release from ER, and mitochondrial
      depolarization in parthanatos. Importantly, our results indicated that propofol
      protected cerebral ischemia-reperfusion via parthanatos suppression, amelioration
      of mitochondria, and ER swelling. Our findings provide new insights into the
      mechanisms of how ER and mitochondria contribute to parthanatos. Furthermore, our
      studies elucidated that propofol has a vital role in parthanatos prevention in
      vivo and in vitro, and propofol can be a promising therapeutic approach for nerve
      injury patients.

PMID- 30224700
TI  - A spin torque meter with magnetic facet domains.
AB  - Current-induced magnetic domain wall (DW) motion is an important operating
      principle of spintronic devices. Injected current generates spin torques (STs) on
      the DWs in two ways. One is the spin transfer from magnetic domains to the walls
      by the current flowing in the magnet. Current flow in attached heavy metals also
      generates another ST because of the spin-Hall effect. Both phenomena explain the
      wall motions well; therefore, their respective contribution is an important
      issue. Here, we show the simultaneous measurement of both torques by using
      magnetic facet domains that form mountain-shaped domains with straight walls.
      When the STs and the external magnetic field push the walls in opposite
      directions, the walls should have equilibrium angles to create balanced states.
      Such angles can be modulated by an additional in-plane magnetic field. Angle
      measurements distinguish the STs because each torque has a distinct mechanism
      related to the DW structure.

PMID- 30224701
TI  - Energy cost of entanglement extraction in complex quantum systems.
AB  - What is the energy cost of extracting entanglement from complex quantum systems?
      Operationally, we may wish to actually extract entanglement. Conceptually, we may
      wish to physically understand the entanglement distribution as a function of
      energy. This is important, especially for quantum field theory vacua, which are
      extremely entangled. Here we build a theory to understand the energy cost of
      entanglement extraction. First, we consider a toy model, and then we define the
      entanglement temperature, relating energy cost to extracted entanglement. Next,
      we give a physical argument quantifying the energy cost of entanglement
      extraction in some quantum field vacua. There the energy cost depends on the
      spatial dimension: in one dimension, for example, it grows exponentially with
      extracted entanglement. Next, we provide approaches to bound the energy cost of
      extracting entanglement more generally. Finally, we look at spin chain models
      numerically to calculate the entanglement temperature using matrix product
      states.

PMID- 30224702
TI  - The complex underpinnings of genetic background effects.
AB  - Genetic interactions between mutations and standing polymorphisms can cause
      mutations to show distinct phenotypic effects in different individuals. To
      characterize the genetic architecture of these so-called background effects, we
      genotype 1411 wild-type and mutant yeast cross progeny and measure their growth
      in 10 environments. Using these data, we map 1086 interactions between
      segregating loci and 7 different gene knockouts. Each knockout exhibits between
      73 and 543 interactions, with 89% of all interactions involving higher-order
      epistasis between a knockout and multiple loci. Identified loci interact with as
      few as one knockout and as many as all seven knockouts. In mutants, loci
      interacting with fewer and more knockouts tend to show enhanced and reduced
      phenotypic effects, respectively. Cross-environment analysis reveals that most
      interactions between the knockouts and segregating loci also involve the
      environment. These results illustrate the complicated interactions between
      mutations, standing polymorphisms, and the environment that cause background
      effects.

PMID- 30224703
TI  - Publisher Correction: Melting conditions in the modern Tibetan crust since the
      Miocene.
AB  - The original PDF version of this Article contained an error in which Fig. 3 and
      its legend were omitted and Equations 5 and 6 contained errors.This has been
      corrected in the PDF version of the Article. The HTML version was correct from
      the time of publication.

PMID- 30224704
TI  - Preconditioning the uterine unfolded protein response maintains non-apoptotic
      Caspase 3-dependent quiescence during pregnancy.
AB  - The prevention of apoptotic caspase 3 activation through biological
      preconditioning, mediated through the modulation of the unfolded protein response
      has been demonstrated to ameliorate multiple pathophysiologies. The maintenance
      of non-apoptotic caspase 3 activity by the unfolded protein response within the
      pregnant uterus has previously been proven to be critical in inhibiting uterine
      myocyte contractility during pregnancy. Here we report that the pregnant uterus
      utilizes an unfolded protein response-preconditioning paradigm to conserve
      myometrial caspase 3 in a non-apoptotic state in order to effectively inhibit
      uterine contractility thereby preventing the onset of preterm labor. In the
      absence of appropriate endogenous preconditioning during pregnancy, uterine
      caspase 3 is transformed from a non-apoptotic to an apoptotic phenotype.
      Apoptotic caspase 3 activation results in the precocious triggering of local
      uterine inflammatory signaling and prostaglandin production, consequently
      resulting in an increased incidence of preterm birth. These findings represent a
      paradigm shift in our understanding of how preconditioning promotes the
      maintenance of uterine non-apoptotic caspase 3 action during pregnancy preventing
      the onset of premature uterine contraction and therefore defining the timing of
      the onset of labor.

PMID- 30224705
TI  - Anterior-posterior gradient of plasticity in primate prefrontal cortex.
AB  - The functional organization of the primate prefrontal cortex has been a matter of
      debate with some models speculating dorso-ventral and rostro-caudal
      specialization while others suggesting that information is represented
      dynamically by virtue of plasticity across the entire prefrontal cortex. To
      address functional properties and capacity for plasticity, we recorded from
      different prefrontal sub-regions and analyzed changes in responses following
      training in a spatial working memory task. This training induces more pronounced
      changes in anterior prefrontal regions, including increased firing rate during
      the delay period, selectivity, reliability, information for stimuli,
      representation of whether a test stimulus matched the remembered cue or not, and
      variability and correlation between neurons. Similar results are obtained for
      discrete subdivisions or when treating position along the anterior-posterior axis
      as a continuous variable. Our results reveal that anterior aspects of the lateral
      prefrontal cortex of non-human primates possess greater plasticity based on task
      demands.

PMID- 30224706
TI  - sox9b is required in cardiomyocytes for cardiac morphogenesis and function.
AB  - The high mobility group transcription factor SOX9 is expressed in stem cells,
      progenitor cells, and differentiated cell-types in developing and mature organs.
      Exposure to a variety of toxicants including dioxin, di(2-ethylhexyl) phthalate,
      6:2 chlorinated polyfluorinated ether sulfonate, and chlorpyrifos results in the
      downregulation of tetrapod Sox9 and/or zebrafish sox9b. Disruption of Sox9/sox9b
      function through environmental exposures or genetic mutations produce a wide
      range of phenotypes and adversely affect organ development and health. We
      generated a dominant-negative sox9b (dnsox9b) to inhibit sox9b target gene
      expression and used the Gal4/UAS system to drive dnsox9b specifically in
      cardiomyocytes. Cardiomyocyte-specific inhibition of sox9b function resulted in a
      decrease in ventricular cardiomyocytes, an increase in atrial cardiomyocytes,
      hypoplastic endothelial cushions, and impaired epicardial development, ultimately
      culminating in heart failure. Cardiomyocyte-specific dnsox9b expression
      significantly reduced end diastolic volume, which corresponded with a decrease in
      stroke volume, ejection fraction, and cardiac output. Further analysis of
      isolated cardiac tissue by RT-qPCR revealed cardiomyocyte-specific inhibition of
      sox9b function significantly decreased the expression of the critical cardiac
      development genes nkx2.5, nkx2.7, and myl7, as well as c-fos, an immediate early
      gene necessary for cardiomyocyte progenitor differentiation. Together our studies
      indicate sox9b transcriptional regulation is necessary for cardiomyocyte
      development and function.

PMID- 30224707
TI  - A plant Bro1 domain protein BRAF regulates multivesicular body biogenesis and
      membrane protein homeostasis.
AB  - Plant development, defense, and many physiological processes rely on the
      endosomal sorting complex required for transport (ESCRT) machinery to control the
      homeostasis of membrane proteins by selective vacuolar degradation. Although
      ESCRT core components are conserved among higher eukaryotes, the regulators that
      control the function of the ESCRT machinery remain elusive. We recently
      identified a plant-specific ESCRT component, FREE1, that is essential for
      multivesicular body/prevacuolar compartment (MVB/PVC) biogenesis and vacuolar
      sorting of membrane proteins. Here we identify a plant-specific Bro1-domain
      protein BRAF, which regulates FREE1 recruitment to the MVB/PVC membrane by
      competitively binding to the ESCRT-I component Vps23. Altogether, we have
      successfully identified a role for BRAF, whose function as a unique evolutionary
      ESCRT regulator in orchestrating intraluminal vesicle formation in MVB/PVCs and
      the sorting of membrane proteins for degradation in plants makes it an important
      regulatory mechanism underlying the ESCRT machinery in higher eukaryotes.

PMID- 30224708
TI  - Grading facial expression is a sensitive means to detect grimace differences in
      orofacial pain in a rat model.
AB  - Although pre-clinical models of pain are useful for defining relationships
      between biological mechanisms and pain, common methods testing peripheral
      sensitivity do not translate to the human pain experience. Facial grimace scales
      evaluate affective pain levels in rodent models by capturing and scoring
      spontaneous facial expression. But, the Rat Grimace Scale (RGS) has not assessed
      the common disorder of temporomandibular joint (TMJ) pain. A rat model of TMJ
      pain induced by jaw loading (1 hr/day for 7 days) was used to investigate the
      time course of RGS scores and compare them between different loading magnitudes
      with distinct peripheral sensitivity profiles (0N-no sensitivity, 2N-acute
      sensitivity, 3.5N-persistent sensitivity). In the 3.5N group, RGS is elevated
      over baseline during the loading period and one day after loading and is
      correlated with peripheral sensitivity (rho = -0.48, p = 0.002). However, RGS is
      not elevated later when that group exhibits peripheral sensitivity and moderate
      TMJ condylar cartilage degeneration. Acutely, RGS is elevated in the 3.5N loading
      group over the other loading groups (p < 0.001). These findings suggest that RGS
      is an effective tool for detecting spontaneous TMJ pain and that spontaneous pain
      is detectable in rats that develop persistent TMJ sensitivity, but not in rats
      with acute resolving sensitivity.

PMID- 30224709
TI  - Establishment of stable iPS-derived human neural stem cell lines suitable for
      cell therapies.
AB  - Establishing specific cell lineages from human induced pluripotent stem cells
      (hiPSCs) is vital for cell therapy approaches in regenerative medicine,
      particularly for neurodegenerative disorders. While neural precursors have been
      induced from hiPSCs, the establishment of hiPSC-derived human neural stem cells
      (hiNSCs), with characteristics that match foetal hNSCs and abide by cGMP
      standards, thus allowing clinical applications, has not been described. We
      generated hiNSCs by a virus-free technique, whose properties recapitulate those
      of the clinical-grade hNSCs successfully used in an Amyotrophic Lateral Sclerosis
      (ALS) phase I clinical trial. Ex vivo, hiNSCs critically depend on exogenous
      mitogens for stable self-renewal and amplification and spontaneously
      differentiate into astrocytes, oligodendrocytes and neurons upon their removal.
      In the brain of immunodeficient mice, hiNSCs engraft and differentiate into
      neurons and glia, without tumour formation. These findings now warrant the
      establishment of clinical-grade, autologous and continuous hiNSC lines for
      clinical trials in neurological diseases such as Huntington's, Parkinson's and
      Alzheimer's, among others.

PMID- 30224710
TI  - Attentional Guidance from Multiple Working Memory Representations: Evidence from
      Eye Movements.
AB  - Recent studies have shown that the representation of an item in visual working
      memory (VWM) can bias the deployment of attention to stimuli in the visual scene
      possessing the same features. When multiple item representations are
      simultaneously held in VWM, whether these representations, especially those held
      in a non-prioritized or accessory status, are able to bias attention, is still
      controversial. In the present study we adopted an eye tracking technique to shed
      light on this issue. In particular, we implemented a manipulation aimed at
      prioritizing one of the VWM representation to an active status, and tested
      whether attention could be guided by both the prioritized and the accessory
      representations when they reappeared as distractors in a visual search task.
      Notably, in Experiment 1, an analysis of first fixation proportion (FFP) revealed
      that both the prioritized and the accessory representations were able to capture
      attention suggesting a significant attentional guidance effect. However, such
      effect was not present in manual response times (RT). Most critically, in
      Experiment 2, we used a more robust experimental design controlling for different
      factors that might have played a role in shaping these findings. The results
      showed evidence for attentional guidance from the accessory representation in
      both manual RTs and FFPs. Interestingly, FFPs showed a stronger attentional bias
      for the prioritized representation than for the accessory representation across
      experiments. The overall findings suggest that multiple VWM representations, even
      the accessory representation, can simultaneously interact with visual attention.

PMID- 30224711
TI  - Concyclic CH-pi arrays for single-axis rotations of a bowl in a tube.
AB  - The hydrogen bond is undoubtedly one of the most important non-covalent
      interactions. Among the several types of the hydrogen bonds, the CH-pi
      interaction is a relatively new notion that is being recognised in chemistry and
      biology. Although the CH-pi hydrogen bond and conventional hydrogen bonds share
      common features such as directionality, this weak interaction has played a
      secondary role in molecular recognition. In this study, we have devised a host
      guest complex that is assembled solely by the CH-pi hydrogen bonds. Multivalent
      interactions of a bowl-shaped hydrocarbon with its peripheral hydrogen atoms are
      made possible via CH-pi hydrogen bonds by adopting a tubular hydrocarbon as a
      host for their enthalpy-driven complexation. Concyclic arrays of weak hydrogen
      bonds further allow dynamic rotational motions of the guest in the host. Solid
      state analysis with crystallographic and spectroscopic methods reveal a single
      axis rotation of the bowl in the tube.

PMID- 30224712
TI  - Neuropeptide Initiated Mast Cell Activation by Transcutaneous Electrical Acupoint
      Stimulation of Acupoint LI4 in Rats.
AB  - Transcutaneous electrical acupoint stimulation (TEAS) has been consistently used
      clinically for its ease of operation, non-invasiveness and painlessness, in
      contrast to the characteristics of inserted needles. However, the mechanism
      remains unknown. The aim of this study was to investigate the local response of
      TEAS at Hegu acupoint (LI4). Immunohistochemistry was used to measure the
      expression of tryptase-positive mast cells, neuropeptides of the calcitonin gene
      related peptide (CGRP) and substance P (SP) in LI4. Mast cells were also labelled
      with serotonin (5-HT), neurokinin-1 receptor (NK-1R) and toluidine blue. The
      results showed that cutaneous CGRP and SP immune-positive (CGRP-IP or SP-IP)
      nerve fibres in LI4 were more highly expressed. There were high degrees of mast
      cell aggregation and degranulation with release of 5-HT near the CGRP-IP or SP-IP
      nerve fibres and blood vessels after TEAS. The degranulation of mast cells (MCs)
      was accompanied by expression of NK-1R after TEAS. Either mast cell membrane
      stabilizer (Disodium cromoglycate) or NK-1R antagonist (RP 67580) diminished the
      accumulation and degranulation of MCs induced by TEAS. Taken together, the
      findings demonstrated that TEAS induced sensory nerve fibres to express CGRP and
      SP, which then bound to the NK-1R on MCs, after which MCs degranulated and
      released 5-HT, resulting in TEAS-initiated acupuncture-like signals.

PMID- 30224713
TI  - An incoherent feed-forward loop switches the Arabidopsis clock rapidly between
      two hysteretic states.
AB  - In higher plants (e.g., Arabidopsis thaliana), the core structure of the
      circadian clock is mostly governed by a repression process with very few direct
      activators. With a series of simplified models, we studied the underlying
      mechanism and found that the Arabidopsis clock consists of type-2 incoherent feed
      forward loops (IFFLs), one of them creating a pulse-like expression in PRR9/7.
      The double-negative feedback loop between CCA1/LHY and PRR5/TOC1 generates a
      bistable, hysteretic behavior in the Arabidopsis circadian clock. We found that
      the IFFL involving PRR9/7 breaks the bistability and moves the system forward
      with a rapid pulse in the daytime, and the evening complex (EC) breaks it in the
      evening. With this illustration, we can intuitively explain the behavior of the
      clock under mutant conditions. Thus, our results provide new insights into the
      underlying network structures of the Arabidopsis core oscillator.

PMID- 30224714
TI  - Mesocosm experiments reveal the impact of mosquito control measures on malaria
      vector life history and population dynamics.
AB  - The impact of control measures on mosquito vector fitness and demography is
      usually estimated from bioassays or indirect variables in the field. Whilst
      indicative, neither approach is sufficient to quantify the potentially complex
      response of mosquito populations to combined interventions. Here, large
      replicated mesocosms were used to measure the population-level response of the
      malaria vector Anopheles arabiensis to long-lasting insecticidal nets (LLINs)
      when used in isolation, or combined with insecticidal eave louvers (EL), or
      treatment of cattle with the endectocide Ivermectin (IM). State-space models
      (SSM) were fit to these experimental data, revealing that LLIN introduction
      reduced adult mosquito survival by 91% but allowed population persistence. ELs
      provided no additional benefit, but IM reduced mosquito fecundity by 59% and
      nearly eliminated all populations when combined with LLINs. This highlights the
      value of IM for integrated vector control, and mesocosm population experiments
      combined with SSM for identifying optimal combinations for vector population
      elimination.

PMID- 30224716
TI  - Attenuation of melanogenesis by Nymphaea nouchali (Burm. f) flower extract
      through the regulation of cAMP/CREB/MAPKs/MITF and proteasomal degradation of
      tyrosinase.
AB  - Medicinal plants have been used to treat diseases from time immemorial. We aimed
      to examine the efficacy of the ethyl acetate fraction of Nymphaea nouchali flower
      extract (NNFE) against melanogenesis process, and the underlying mechanisms in
      vitro and in vivo. Paper spray ionisation mass spectroscopy and (+) mode
      electrospray ionisation revealed the presence of seven flavonoids, two spermidine
      alkaloids, 3,4,8,9,10-pentahydroxy-dibenzo[b,d]pyran-6-one, and shoyuflavone C in
      NNFE. NNFE (100 ug/mL) significantly inhibited the monophenolase and diphenolase
      activities of mushroom tyrosinase at 94.90 +/- 0.003% and 93.034 +/- 0.003%,
      respectively. NNFE significantly suppressed cellular tyrosinase activity and
      melanin synthesis in vitro in melan-a cells and in vivo in HRM2 hairless mice.
      Furthermore, NNFE inhibited tyrosinase (TYR), tyrosinase-related protein (TYRP)
      1, TYRP-2, and microphthalmia-associated transcription factor (MITF) expression,
      thereby blocking melanin synthesis. In particular, NNFE suppressed cAMP
      production with subsequent downregulation of CREB phosphorylation. Additionally,
      it stimulated MAP kinase phosphorylation (p38, JNK, and ERK1/2) and the
      proteasomal debasement pathway, leading to degradation of tyrosinase and MITF and
      the suppression of melanin production. Moreover, selective inhibitors of ERK1/2,
      JNK, and p38 attenuated NNFE inhibitory effects on melanogenesis, and MG-132 (a
      proteasome inhibitor) prevented the NNFE-induced decline in tyrosinase protein
      levels. In conclusion, these findings indicate that NNFE is a potential therapy
      for hyperpigmentation.

PMID- 30224715
TI  - Ring synthetic chromosome V SCRaMbLE.
AB  - Structural variations (SVs) exert important functional impacts on biological
      phenotypic diversity. Here we show a ring synthetic yeast chromosome V
      (ring_synV) can be used to continuously generate complex genomic variations and
      improve the production of prodeoxyviolacein (PDV) by applying Synthetic
      Chromosome Recombination and Modification by LoxP-mediated Evolution (SCRaMbLE)
      in haploid yeast cells. The SCRaMbLE of ring_synV generates aneuploid yeast
      strains with increased PDV productivity, and we identify aneuploid chromosome I,
      III, VI, XII, XIII, and ring_synV. The neochromosome of SCRaMbLEd ring_synV
      generated more unbalanced forms of variations, including duplication, insertions,
      and balanced forms of translocations and inversions than its linear form.
      Furthermore, of the 29 novel SVs detected, 11 prompted the PDV biosynthesis; and
      the deletion of uncharacterized gene YER182W is related to the improvement of the
      PDV. Overall, the SCRaMbLEing ring_synV embraces the evolution of the genome by
      modifying the chromosome number, structure, and organization, identifying targets
      for phenotypic comprehension.

PMID- 30224717
TI  - Copper-to-copper direct bonding on highly (111)-oriented nanotwinned copper in no
      vacuum ambient.
AB  - A vacuum-free Cu-to-Cu direct bonding by using (111)-oriented and nanotwinned Cu
      has been achieved. A fast bonding process occurs in 5 min under a temperature
      gradient between 450 and 100  degrees C. It is verified by grain growth across
      the bonded interface. To investigate the grain growth behavior, further annealing
      in the temperature gradient, as well as in a reversed temperature gradient, was
      performed. They showed similar recrystallization behavior with de-twinning. To
      analyze the de-twinning, we recall the classic model of annealing twin formation
      by Fullman and Fisher as comparison. Our case is opposite to the model of Fullman
      and Fisher. A mechanism of direct bonding by surface diffusion creep is proposed.

PMID- 30224718
TI  - Idelalisib promotes Bim-dependent apoptosis through AKT/FoxO3a in hepatocellular
      carcinoma.
AB  - Idelalisib, a selective PI3Kdelta inhibitor, has been approved by the FDA for
      chronic lymphocytic leukemia/small lymphocytic lymphoma treatment and for
      follicular lymphoma treatment when combined with rituximab. However, the
      mechanisms of effective action of idelalisib in hepatocellular carcinoma (HCC)
      remain unclear. In the current study, we aimed to investigate how idelalisib
      inhibits the growth of HCC cells and enhances the effects of other
      chemotherapeutic drugs. Our results show that idelalisib treatment promotes Bim
      induction in HCC via the FoxO3a pathway following PI3K/AKT inactivation.
      Moreover, our results show that Bim is required for idelalisib-mediated apoptosis
      in HCC. Idelalisib also synergizes with sorafenib or doxorubicin to induce
      significant apoptosis in HCC, and Bim is also necessary for the induction of
      apoptosis by cotreatment. Furthermore, a xenograft experiment reveals that the
      Bim deficiency abolishes apoptosis and antitumor effects of idelalisib in vivo.
      In summary, our results indicate a key role of Bim in mediating the antitumor
      effects of idelalisib in HCC. Our results also support the clinical significance
      of the drug.

PMID- 30224719
TI  - Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma
      due to cell cycle regulation and cellular stress.
AB  - Encoded by EEF1A1, the eukaryotic translation elongation factor eEF1alpha1
      strongly promotes the heat shock response, which protects cancer cells from
      proteotoxic stress, following for instance oxidative stress, hypoxia or
      aneuploidy. Unexpectedly, therefore, we find that EEF1A1 mRNA levels are reduced
      in virtually all breast cancers, in particular in ductal carcinomas. Univariate
      and multivariate analyses indicate that EEF1A1 mRNA underexpression independently
      predicts poor patient prognosis for estrogen receptor-positive (ER+) cancers.
      EEF1A1 mRNA levels are lowest in the most invasive, lymph node-positive, advanced
      stage and postmenopausal tumors. In sharp contrast, immunohistochemistry on 100
      ductal breast carcinomas revealed that at the protein level eEF1alpha1 is
      ubiquitously overexpressed, especially in ER+ , progesterone receptor-positive
      and lymph node-negative tumors. Explaining this paradox, we find that EEF1A1 mRNA
      levels in breast carcinomas are low due to EEF1A1 allelic copy number loss, found
      in 27% of tumors, and cell cycle-specific expression, because mRNA levels are
      high in G1 and low in proliferating cells. This also links estrogen-induced cell
      proliferation to clinical observations. In contrast, high eEF1alpha1 protein
      levels protect tumor cells from stress-induced cell death. These observations
      suggest that, by obviating EEF1A1 transcription, cancer cells can rapidly induce
      the heat shock response following proteotoxic stress, and survive.

PMID- 30224721
TI  - Author Correction: Snail collaborates with EGR-1 and SP-1 to directly activate
      transcription of MMP 9 and ZEB1.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30224720
TI  - Ginseng oligopeptides protect against irradiation-induced immune dysfunction and
      intestinal injury.
AB  - Intestinal injury and immune dysfunction are commonly encountered after
      irradiation therapy. While the curative abilities of ginseng root have been
      reported in prior studies, there is little known regarding its role in
      immunoregulation of intestinal repairability in cancer patients treated with
      irradiation. Our current study aims to closely examine the protective effects of
      ginseng-derived small molecule oligopeptides (Panax ginseng C. A. Mey.) (GOP)
      against irradiation-induced immune dysfunction and subsequent intestinal injury,
      using in vitro and in vivo models. Expectedly, irradiation treatment resulted in
      increased intestinal permeability along with mucosal injury in both Caco-2 cells
      and mice, probably due to disruption of the intestinal epithelial barrier,
      leading to high plasma lipopolysaccharide (LPS) and pro-inflammatory cytokines
      levels. However, when the cells were treated with GOP, this led to diminished
      concentration of plasma LPS and cytokines (IL-1 and TNF-alpha), suggesting its
      dampening effect on inflammatory and oxidative stress, and potential role in
      restoring normal baseline intestinal permeability. Moreover, the Caco-2 cells
      treated with GOP showed high trans-epithelial electrical resistance (TEER) and
      low FITC-dextran paracellular permeability when compared to the control group.
      This could be explained by the higher levels of tight junction proteins (ZO-1 and
      Occludin) expression along with reduced expression of the apoptosis-related
      proteins (Bax and Caspase-3) noticed in the GOP-treated cells, highlighting its
      role in preserving intestinal permeability, through prevention of their
      degradation while maintaining normal levels of expression. Further confirmatory
      in vivo data showed that GOP-treated mice exhibited high concentrations of
      lymphocytes (CD3+, CD4+, CD8+) in the intestine, to rescue the irradiation
      induced damage and restore baseline intestinal integrity. Therefore, we propose
      that GOP can be used as an adjuvant therapy to attenuate irradiation-induced
      immune dysfunction and intestinal injury in cancer patients.

PMID- 30224722
TI  - Identification of a molecular locus for normalizing dysregulated GABA release
      from interneurons in the Fragile X brain.
AB  - Principal neurons encode information by varying their firing rate and patterns
      precisely fine-tuned through GABAergic interneurons. Dysregulation of inhibition
      can lead to neuropsychiatric disorders, yet little is known about the molecular
      basis underlying inhibitory control. Here, we find that excessive GABA release
      from basket cells (BCs) attenuates the firing frequency of Purkinje neurons (PNs)
      in the cerebellum of Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mice, a
      model of Fragile X Syndrome (FXS) with abrogated expression of the Fragile X
      Mental Retardation Protein (FMRP). This over-inhibition originates from increased
      excitability and Ca2+ transients in the presynaptic terminals, where Kv1.2
      potassium channels are downregulated. By paired patch-clamp recordings, we
      further demonstrate that acutely introducing an N-terminal fragment of FMRP into
      BCs normalizes GABA release in the Fmr1-KO synapses. Conversely, direct injection
      of an inhibitory FMRP antibody into BCs, or membrane depolarization of BCs,
      enhances GABA release in the wild type synapses, leading to abnormal inhibitory
      transmission comparable to the Fmr1-KO neurons. We discover that the N-terminus
      of FMRP directly binds to a phosphorylated serine motif on the C-terminus of
      Kv1.2; and that loss of this interaction in BCs exaggerates GABA release,
      compromising the firing activity of PNs and thus the output from the cerebellar
      circuitry. An allosteric Kv1.2 agonist, docosahexaenoic acid, rectifies the
      dysregulated inhibition in vitro as well as acoustic startle reflex and social
      interaction in vivo of the Fmr1-KO mice. Our results unravel a novel molecular
      locus for targeted intervention of FXS and perhaps autism.

PMID- 30224723
TI  - Spatio-temporal characteristics of population responses evoked by
      microstimulation in the barrel cortex.
AB  - Intra-cortical microstimulation (ICMS) is a widely used technique to artificially
      stimulate cortical tissue. This method revealed functional maps and provided
      causal links between neuronal activity and cognitive, sensory or motor functions.
      The effects of ICMS on neural activity depend on stimulation parameters. Past
      studies investigated the effects of stimulation frequency mainly at the
      behavioral or motor level. Therefore the direct effect of frequency stimulation
      on the evoked spatio-temporal patterns of cortical activity is largely unknown.
      To study this question we used voltage-sensitive dye imaging to measure the
      population response in the barrel cortex of anesthetized rats evoked by high
      frequency stimulation (HFS), a lower frequency stimulation (LFS) of the same
      duration or a single pulse stimulation. We found that single pulse and short
      trains of ICMS induced cortical activity extending over few mm. HFS evoked a
      lower population response during the sustained response and showed a smaller
      activation across time and space compared with LFS. Finally the evoked population
      response started near the electrode site and spread horizontally at a propagation
      velocity in accordance with horizontal connections. In summary, HFS was less
      effective in cortical activation compared to LFS although HFS had 5 fold more
      energy than LFS.

PMID- 30224725
TI  - Neogene fluvial landscape evolution in the hyperarid core of the Atacama Desert.
AB  - Dating of extensive alluvial fan surfaces and fluvial features in the hyperarid
      core of the Atacama Desert, Chile, using cosmogenic nuclides provides unrivalled
      insights about the onset and variability of aridity. The predominantly hyperarid
      conditions help to preserve the traces of episodic climatic and/or slow tectonic
      change. Utilizing single clast exposure dating with cosmogenic 10Be and 21Ne, we
      determine the termination of episodes of enhanced fluvial erosion and deposition
      occurring at ~19, ~14, ~9.5 Ma; large scale fluvial modification of the landscape
      had ceased by ~2-3 Ma. The presence of clasts that record pre-Miocene exposure
      ages (~28 Ma and ~34 Ma) require stagnant landscape development during the
      Oligocene. Our data implies an early onset of (hyper-) aridity in the core region
      of the Atacama Desert, interrupted by wetter but probably still arid periods. The
      apparent conflict with interpretation that favour a later onset of (hyper-)
      aridity can be reconciled when the climatic gradients within the Atacama Desert
      are considered.

PMID- 30224724
TI  - 14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a
      hydrophobic surface.
AB  - Pseudomonas are a common cause of hospital-acquired infections that may be
      lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend
      on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide
      binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought
      to be crucial for their activation. However, crystal structures of the 14-3
      3beta:ExoS and -ExoT complexes presented here reveal an extensive hydrophobic
      interface that is sufficient for complex formation and toxin activation. We show
      that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the
      amphipathic binding motif is active when co-expressed with 14-3-3. Moreover,
      swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates
      a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we
      show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this
      indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains
      by chaperoning their hydrophobic surfaces independently of the amphipathic C
      terminal segment.

PMID- 30224727
TI  - Tissue 'melting' sculpts embryo.

PMID- 30224726
TI  - Kidney-resident macrophages promote a proangiogenic environment in the normal and
      chronically ischemic mouse kidney.
AB  - Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by
      microvascular damage. Macrophages are implicated in repair and injury, but the
      specific populations responsible for these divergent roles have not been
      identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three
      transcriptionally unique populations. Using fate-mapping and parabiosis studies,
      we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while
      CD11chiMphi, CD11cloMphi are monocyte-derived macrophages. In a murine model of
      RAS, KRM self-renewed, while CD11chiMphi and CD11cloMphi increased significantly,
      which was associated with loss of peritubular capillaries. Replacing the native
      KRM with monocyte-derived KRM using liposomal clodronate and bone marrow
      transplantation followed by RAS, amplified loss of peritubular capillaries. To
      further elucidate the nature of interactions between KRM and peritubular
      endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from
      Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with
      significant enrichment in reparative pathways, like angiogenesis and wound
      healing. In culture, KRM increased proliferation of renal peritubular endothelial
      cells implying direct pro-angiogenic properties. Human homologs of KRM identified
      as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS
      patients compared to healthy human kidneys, and inversely correlated to kidney
      function. Thus, KRM may play protective roles in stenotic kidney injury through
      expansion and upregulation of pro-angiogenic pathways.

PMID- 30224728
TI  - T cells engineered to home in on brain cancer.

PMID- 30224729
TI  - Bird forecasting by radar.

PMID- 30224730
TI  - Protein structures guide the design of a much-needed tool for neuroscience.

PMID- 30224731
TI  - Reducing neuronal inhibition restores locomotion in paralysed mice.

PMID- 30224733
TI  - Immobilizing Laccase on Different Species Wood Biochar to Remove the Chlorinated
      Biphenyl in Wastewater.
AB  - Biochars produced from two different wood species over a microwave assisted
      pyrolysis process were used as novel and green-based supports for immobilizing
      enzyme, laccase in particular. The results obtained from FT-IR, SEM and BET
      measurements indicated that Maple biochar with honeycomb structure has higher
      surface area and pore volume than Spruce biochar; and there exist O-H, C-H, C=O
      and C=C groups in biochars for potential chemical modification. The best laccase
      immobilization conditions identified from an orthogonal experiment were pH = 3,
      laccase concentration 16 g/L and contact time 8 h. Under such conditions, the
      high immobilization yield (64.2%) and amount (11.14 mg/g) of laccase on Maple
      biochar were achieved, leading to the significantly improved thermal stability of
      laccase. Moreover, the immobilized laccase is reusable and enhanced the enzymatic
      degradation of 4-hydroxy-3,5-dichlorobiphenyl (71.4% yield), thus creating a
      promising and novel type of adsorbent in the removal of polychlorinated biphenyls
      from wastewater.

PMID- 30224732
TI  - Immobilization stress-induced Escherichia coli causes anxiety by inducing NF
      kappaB activation through gut microbiota disturbance.
AB  - The present study aimed to understand the crosstalk between anxiety and gut
      microbiota. Exposure of mice to immobilization stress (IS) led to anxiety-like
      behaviors, increased corticosterone and tumor necrosis factor-alpha levels in the
      blood, increased nuclear factor (NF)-kappaB activation and microglia/monocyte
      populations in the hippocampus, and suppressed brain-derived neurotrophic factor
      (BDNF) expression in the hippocampus. Furthermore, IS exposure increased NF
      kappaB activation and monocyte population in the colon and increased
      Proteobacteria and Escherichia coli populations in the gut microbiota and fecal
      and blood lipopolysaccharide (LPS) levels while decreasing the lactobacilli
      population. Oral administration of the fecal microbiota of mice treated with IS
      (FIS) or E. coli led to the increased NF-kappaB activation and monocyte
      population in the colon. These treatments increased blood corticosterone and LPS
      levels and anxiety-like behaviors, decreased BDNF expression, and induced NF
      kappaB activation and microglia/monocyte populations in the hippocampus.
      Intraperitoneal injection of LPS purified from E. coli also led to anxiety and
      colitis in mice. Oral administration of commensal lactobacilli, particularly
      Lactobacillus johnsonii, attenuated IS- or E. coli-induced colitis and anxiety
      like behaviors and biomarkers. These findings suggest that exposure to stressors
      can increase Proteobacteria populations and fecal LPS levels and cause
      gastrointestinal inflammation, resulting in the deterioration of anxiety through
      NF-kappaB activation. However, the amelioration of gastrointestinal inflammation
      by treatment with probiotics including L. johnsonii can alleviate anxiety.

PMID- 30224734
TI  - Highly tunable repetition-rate multiplication of mode-locked lasers using all
      fibre harmonic injection locking.
AB  - Higher repetition-rate optical pulse trains have been desired for various
      applications such as high-bit-rate optical communication, photonic analogue-to
      digital conversion, and multi-photon imaging. Generation of multi GHz and higher
      repetition-rate optical pulse trains directly from mode-locked oscillators is
      often challenging. As an alternative, harmonic injection locking can be applied
      for extra-cavity repetition-rate multiplication (RRM). Here we have investigated
      the operation conditions and achievable performances of all-fibre, highly tunable
      harmonic injection locking-based pulse RRM. We show that, with slight tuning of
      slave laser length, highly tunable RRM is possible from a multiplication factor
      of 2 to >100. The resulting maximum SMSR is 41 dB when multiplied by a factor of
      two. We further characterize the noise properties of the multiplied signal in
      terms of phase noise and relative intensity noise. The resulting absolute rms
      timing jitter of the multiplied signal is in the range of 20 fs to 60 fs (10 kHz
      1MHz) for different multiplication factors. With its high tunability, simple and
      robust all-fibre implementation, and low excess noise, the demonstrated RRM
      system may find diverse applications in microwave photonics, optical
      communications, photonic analogue-to-digital conversion, and clock distribution
      networks.

PMID- 30224735
TI  - A specific, promoter-independent activity of T7 RNA polymerase suggests a general
      model for DNA/RNA editing in single subunit RNA Polymerases.
AB  - Insertional RNA editing has been observed and characterized in mitochondria of
      myxomycetes. The single subunit mitochondrial RNA polymerase adds nontemplated
      nucleotides co-transcriptionally to produce functional tRNA, rRNA and mRNAs with
      full genetic information. Addition of nontemplated nucleotides to the 3' ends of
      RNAs have been observed in polymerases related to the mitochondrial RNA
      polymerase. This activity has been observed with T7 RNA polymerase (T7 RNAP), the
      well characterized prototype of the single subunit polymerases, as a nonspecific
      addition of nucleotides to the 3' end of T7 RNAP transcripts in vitro. Here we
      show that this novel activity is an editing activity that can add specific
      ribonucleotides to 3' ends of RNA or DNA when oligonucleotides, able to form
      intramolecular or intermolecular hairpin loops with recessed 3' ends, are added
      to T7 RNA polymerase in the presence of at least one ribonucleotide triphosphate.
      Specific ribonucleotides are added to the recessed 3' ends through Watson-Crick
      base pairing with the non-base paired nucleotide adjacent to the 3' end.
      Optimization of this activity is obtained through alteration of the lengths of
      the 5'-extension, hairpin loop, and hairpin duplex. These properties define a T7
      RNAP activity different from either transcriptional elongation or initiation.

PMID- 30224736
TI  - Structural basis of the filamin A actin-binding domain interaction with F-actin.
AB  - Actin-cross-linking proteins assemble actin filaments into higher-order
      structures essential for orchestrating cell shape, adhesion, and motility.
      Missense mutations in the tandem calponin homology domains of their actin-binding
      domains (ABDs) underlie numerous genetic diseases, but a molecular understanding
      of these pathologies is hampered by the lack of high-resolution structures of any
      actin-cross-linking protein bound to F-actin. Here, taking advantage of a high
      affinity, disease-associated mutant of the human filamin A (FLNa) ABD, we combine
      cryo-electron microscopy and functional studies to reveal at near-atomic
      resolution how the first calponin homology domain (CH1) and residues immediately
      N-terminal to it engage actin. We further show that reorientation of CH2 relative
      to CH1 is required to avoid clashes with actin and to expose F-actin-binding
      residues on CH1. Our data explain localization of disease-associated loss-of
      function mutations to FLNaCH1 and gain-of-function mutations to the regulatory
      FLNaCH2. Sequence conservation argues that this provides a general model for ABD
      F-actin binding.

PMID- 30224737
TI  - Engineered Human Contractile Myofiber Sheets as a Platform for Studies of
      Skeletal Muscle Physiology.
AB  - Skeletal muscle physiology and the mechanisms of muscle diseases can be
      effectively studied by an in-vitro tissue model produced by muscle tissue
      engineering. Engineered human cell-based tissues are required more than ever
      because of the advantages they bring as tissue models in research studies. This
      study reports on a production method of a human skeletal myofiber sheet that
      demonstrates biomimetic properties including the aligned structure of myofibers,
      basement membrane-like structure of the extracellular matrix, and unidirectional
      contractile ability. The contractile ability and drug responsibility shown in
      this study indicate that this engineered muscle tissue has potential as a human
      cell-based tissue model for clinically relevant in-vitro studies in muscle
      physiology and drug discovery. Moreover, this engineered tissue can be used to
      better understand the relationships between mechanical stress and myogenesis,
      including muscle growth and regeneration. In this study, periodic exercise
      induced by continuous electrical pulse stimulation enhanced the contractile
      ability of the engineered myofibers and the secretion of interleukin-6 (IL-6) and
      vascular endothelial growth factor (VEGF) from the exercising myofibers. Since
      the physiology of skeletal muscle is directly related to mechanical stress, these
      features point to application as a tissue model and platform for future
      biological studies of skeletal muscle including muscle metabolism, muscle atrophy
      and muscle regeneration.

PMID- 30224738
TI  - Comparative Investigations of Social Context-Dependent Dominance in Captive
      Chimpanzees (Pan troglodytes) and Wild Tibetan Macaques (Macaca thibetana).
AB  - Theoretical definitions of dominance, how dominance is structured and organized
      in nature, and how dominance is measured have varied as investigators seek to
      classify and organize social systems in gregarious species. Given the variability
      in behavioral measures and statistical methods used to derive dominance rankings,
      we conducted a comparative analysis of dominance using existing statistical
      techniques to analyze dominance ranks, social context-dependent dominance
      structures, the reliability of statistical analyses, and rank predictability of
      dominance structures on other social behaviors. We investigated these topics
      using behavioral data from captive chimpanzees (Pan troglodytes) and wild Tibetan
      macaques (Macaca thibetana). We used a combination of all-occurrence, focal
      animal, and instantaneous scan sampling to collect social, agonistic, and
      associative data from both species. We analyzed our data to derive dominance
      ranks, test rank reliability, and assess cross-context predictability using
      various statistical analyses. Our results indicate context-dependent dominance
      and individual social roles in the captive chimpanzee group, one broadly defined
      dominance structure in the Tibetan macaque group, and high within-context
      analysis reliability but little cross-context predictability. Overall, we suggest
      this approach is preferable over investigations of dominance where only a few
      behavioral metrics and statistical analyses are utilized with little
      consideration of rank reliability or cross-context predictability.

PMID- 30224739
TI  - Hierarchical Aerographite 3D flexible networks hybridized by InP
      micro/nanostructures for strain sensor applications.
AB  - In the present work, we report on development of three-dimensional flexible
      architectures consisting of an extremely porous three-dimensional Aerographite
      (AG) backbone decorated by InP micro/nanocrystallites grown by a single step
      hydride vapor phase epitaxy process. The systematic investigation of the hybrid
      materials by scanning electron microscopy demonstrates a rather uniform spatial
      distribution of InP crystallites without agglomeration on the surface of
      Aerographite microtubular structures. X-ray diffraction, transmission electron
      microscopy and Raman scattering analysis demonstrate that InP crystallites grown
      on bare Aerographite are of zincblende structure, while a preliminary
      functionalization of the Aerographite backbone with Au nanodots promotes the
      formation of crystalline In2O3 nanowires as well as gold-indium oxide core-shell
      nanostructures. The electromechanical properties of the hybrid AG-InP composite
      material are shown to be better than those of previously reported bare AG and AG
      GaN networks. Robustness, elastic behavior and excellent translation of the
      mechanical deformation to variations in electrical conductivity highlight the
      prospects of AG-InP applications in tactile/strain sensors and other device
      structures related to flexible electronics.

PMID- 30224740
TI  - Multidirectional digital scanned light-sheet microscopy enables uniform
      fluorescence excitation and contrast-enhanced imaging.
AB  - Light-sheet fluorescence microscopy (LSFM) has emerged as a powerful method for
      rapid and optically efficient 3D microscopy. Initial LSFM designs utilized a
      static sheet of light, termed selective plane illumination microscopy (SPIM),
      which exhibited shadowing artifacts and deteriorated contrast due to light
      scattering. These issues have been addressed, in part, by multidirectional
      selective plane illumination microscopy (mSPIM), in which rotation of the light
      sheet is used to mitigate shadowing artifacts, and digital scanned light-sheet
      microscopy (DSLM), in which confocal line detection is used to reject scattered
      light. Here we present a simple and passive multidirectional digital scanned
      light-sheet microscopy (mDSLM) architecture that combines the benefits of mSPIM
      and DSLM. By utilizing an elliptical Gaussian beam with increased angular
      diversity in the imaging plane, mDSLM provides mitigation of shadowing artifacts
      and contrast-enhanced imaging of fluorescently labeled samples.

PMID- 30224741
TI  - Effect of inoculated and uninoculated aeration pretreatment on nutrients and
      phytotoxicity of anaerobic digestion effluent.
AB  - This study investigates the influence of inoculated and uninoculated aeration
      pretreatment on nutrients and phytotoxicity of anaerobic digestion (AD) effluent.
      Swine manure AD effluent was inoculated with activated and anaerobic sludge,
      respectively. Our results show that aeration with the addition of activated
      sludge could reduce the phytotoxicity of AD effluent. Compared to the control
      treatment without any sludge addition, the addition of activated sludge resulted
      in a more significant reduction in the AD effluent salinity, NH4+ content, and
      organic matter (indicated by the chemical oxygen demand) when AD effluent was
      aerated for less than 8 hours. As a result, a much higher seed germination index
      (GI) was observed for the treatment with activated sludge addition, particularly
      when aerated for 4-5 hours, contributing the gas/water ratio of 20:1-30:1. On the
      other hand, no significant differences in the nutrient contents and GI value were
      observed for the control treatment and that with the addition of anaerobic
      sludge. Results from this study shed light on optimizing the management of AD
      effluent for agricultural application.

PMID- 30224743
TI  - How morphological development can guide evolution.
AB  - Organisms result from adaptive processes interacting across different time
      scales. One such interaction is that between development and evolution. Models
      have shown that development sweeps over several traits in a single agent,
      sometimes exposing promising static traits. Subsequent evolution can then
      canalize these rare traits. Thus, development can, under the right conditions,
      increase evolvability. Here, we report on a previously unknown phenomenon when
      embodied agents are allowed to develop and evolve: Evolution discovers body plans
      robust to control changes, these body plans become genetically assimilated, yet
      controllers for these agents are not assimilated. This allows evolution to
      continue climbing fitness gradients by tinkering with the developmental programs
      for controllers within these permissive body plans. This exposes a previously
      unknown detail about the Baldwin effect: instead of all useful traits becoming
      genetically assimilated, only traits that render the agent robust to changes in
      other traits become assimilated. We refer to this as differential canalization.
      This finding also has implications for the evolutionary design of artificial and
      embodied agents such as robots: robots robust to internal changes in their
      controllers may also be robust to external changes in their environment, such as
      transferal from simulation to reality or deployment in novel environments.

PMID- 30224742
TI  - Divergent action of fluoxetine in zebrafish according to responsivity to novelty.
AB  - Here we show that the novel object recognition test can discriminate between high
      (HRN, neophobic) and low (LRN, neophilic) novelty responders in zebrafish
      populations. Especially when we observe the latency to the first entry in the
      novel object zone, zebrafish did not maintain these behavioral phenotypes in
      sequential tests and only the HRN group returned to their initial responsive
      behavior when exposed to fluoxetine. Our results have important implications for
      behavioral data analysis since such behavioral differences can potentially
      increase individual response variability and interfere with the outcomes obtained
      from various behavioral tasks. Our data reinforce the validity of personality
      determination in zebrafish since we show clear differences in behavior in
      response to fluoxetine.

PMID- 30224744
TI  - Large-scale mass wasting on small volcanic islands revealed by the study of
      Flores Island (Azores).
AB  - Small intra-plate volcanic islands (total height above seafloor <2500 m) have
      been considered gravitationally stable. Topographic, stratigraphic, structural
      and new K/Ar data show that the small island of Flores (Azores) is strongly
      asymmetric and made up of nested volcanic successions. Along the northwestern
      coastline, ca. 1.2 Ma lava flows are in lateral contact with a younger volcanic
      unit (ca. 0.7 Ma), reflecting the existence of a steep lateral discontinuity.
      From the general dip of the lava flows, their age and the arcuate geometry of the
      contact, we infer a major landslide that removed the western flank of the older
      volcano. Further inland, E-dipping lava flows at the summit of the island are ca.
      1.3 Ma, suggesting another landslide structure that displaced the whole western
      half of the former volcanic edifice. Available offshore data show a large
      hummocky field west of Flores, here interpreted as voluminous debris-avalanche
      deposits. Unlike the eastern and central Azores islands, Flores sits on a
      relatively stable tectonic setting. Therefore, we propose that small-size
      volcanic islands can be sufficiently gravitationally unstable to experience
      recurrent episodes of large-scale mass wasting triggered by mechanisms other than
      tectonic earthquakes and thus represent an under-evaluated potential source of
      hazard and, therefore, risk.

PMID- 30224745
TI  - Structural robustness of mammalian transcription factor networks reveals
      plasticity across development.
AB  - Network biology aims to understand cell behavior through the analysis of
      underlying complex biomolecular networks. Inference of condition-specific
      interaction networks from epigenomic data enables the characterization of the
      structural plasticity that regulatory networks can acquire in different tissues
      of the same organism. From this perspective, uncovering specific patterns of
      variation by comparing network structure among tissues could provide insights
      into systems-level mechanisms underlying cell behavior. Following this idea, here
      we propose an empirical framework to analyze mammalian tissue-specific networks,
      focusing on characterizing and contrasting their structure and behavior in
      response to perturbations. We structurally represent the state of the cell/tissue
      by condition specific transcription factor networks generated using DNase-seq
      chromatin accessibility data, and we profile their systems behavior in terms of
      the structural robustness against random and directed perturbations. Using this
      framework, we unveil the structural heterogeneity existing among tissues at
      different levels of differentiation. We uncover a novel and conserved systems
      property of regulatory networks underlying embryonic stem cells (ESCs): in
      contrast to terminally differentiated tissues, the promiscuous regulatory
      connectivity of ESCs produces a globally homogeneous network resulting in
      increased structural robustness. We show that this property is associated with a
      more permissive, less restrictive chromatin accesibility state in ESCs. Possible
      biological consequences of this property are discussed.

PMID- 30224746
TI  - Sensation, movement and learning in the absence of barrel cortex.
AB  - For many of our senses, the role of the cerebral cortex in detecting stimuli is
      controversial1-17. Here we examine the effects of both acute and chronic
      inactivation of the primary somatosensory cortex in mice trained to move their
      large facial whiskers to detect an object by touch and respond with a lever to
      obtain a water reward. Using transgenic mice, we expressed inhibitory opsins in
      excitatory cortical neurons. Transient optogenetic inactivation of the primary
      somatosensory cortex, as well as permanent lesions, initially produced both
      movement and sensory deficits that impaired detection behaviour, demonstrating
      the link between sensory and motor systems during active sensing. Unexpectedly,
      lesioned mice had recovered full behavioural capabilities by the subsequent
      session. This rapid recovery was experience-dependent, and early re-exposure to
      the task after lesioning facilitated recovery. Furthermore, ablation of the
      primary somatosensory cortex before learning did not affect task acquisition.
      This combined optogenetic and lesion approach suggests that manipulations of the
      sensory cortex may be only temporarily disruptive to other brain structures that
      are themselves capable of coordinating multiple, arbitrary movements with
      sensation. Thus, the somatosensory cortex may be dispensable for active detection
      of objects in the environment.

PMID- 30224747
TI  - Time-asymmetric loop around an exceptional point over the full optical
      communications band.
AB  - Topological operations around exceptional points1-8-time-varying system
      configurations associated with non-Hermitian singularities-have been proposed as
      a robust approach to achieving far-reaching open-system dynamics, as demonstrated
      in highly dissipative microwave transmission3 and cryogenic optomechanical
      oscillator4 experiments. In stark contrast to conventional systems based on
      closed-system Hermitian dynamics, environmental interferences at exceptional
      points are dynamically engaged with their internal coupling properties to create
      rotational stimuli in fictitious-parameter domains, resulting in chiral systems
      that exhibit various anomalous physical phenomena9-16. To achieve new wave
      properties and concomitant device architectures to control them, realizations of
      such systems in application-abundant technological areas, including
      communications and signal processing systems, are the next step. However, it is
      currently unclear whether non-Hermitian interaction schemes can be configured in
      robust technological platforms for further device engineering. Here we
      experimentally demonstrate a robust silicon photonic structure with photonic
      modes that transmit through time-asymmetric loops around an exceptional point in
      the optical domain. The proposed structure consists of two coupled silicon
      channel waveguides and a slab-waveguide leakage-radiation sink that precisely
      control the required non-Hermitian Hamiltonian experienced by the photonic modes.
      The fabricated devices generate time-asymmetric light transmission over an
      extremely broad spectral band covering the entire optical telecommunications
      window (wavelengths between 1.26 and 1.675 micrometres). Thus, we take a step
      towards broadband on-chip optical devices based on non-Hermitian topological
      dynamics by using a semiconductor platform with controllable optoelectronic
      properties, and towards several potential practical applications, such as on-chip
      optical isolators and non-reciprocal mode converters. Our results further suggest
      the technological relevance of non-Hermitian wave dynamics in various other
      branches of physics, such as acoustics, condensed-matter physics and quantum
      mechanics.

PMID- 30224748
TI  - The role of miniaturization in the evolution of the mammalian jaw and middle ear.
AB  - The evolution of the mammalian jaw is one of the most important innovations in
      vertebrate history, and underpins the exceptional radiation and diversification
      of mammals over the last 220 million years1,2. In particular, the transformation
      of the mandible into a single tooth-bearing bone and the emergence of a novel jaw
      joint-while incorporating some of the ancestral jaw bones into the mammalian
      middle ear-is often cited as a classic example of the repurposing of
      morphological structures3,4. Although it is remarkably well-documented in the
      fossil record, the evolution of the mammalian jaw still poses the paradox of how
      the bones of the ancestral jaw joint could function both as a joint hinge for
      powerful load-bearing mastication and as a mandibular middle ear that was
      delicate enough for hearing. Here we use digital reconstructions, computational
      modelling and biomechanical analyses to demonstrate that the miniaturization of
      the early mammalian jaw was the primary driver for the transformation of the jaw
      joint. We show that there is no evidence for a concurrent reduction in jaw-joint
      stress and increase in bite force in key non-mammaliaform taxa in the cynodont
      mammaliaform transition, as previously thought5-8. Although a shift in the
      recruitment of the jaw musculature occurred during the evolution of modern
      mammals, the optimization of mandibular function to increase bite force while
      reducing joint loads did not occur until after the emergence of the neomorphic
      mammalian jaw joint. This suggests that miniaturization provided a selective
      regime for the evolution of the mammalian jaw joint, followed by the integration
      of the postdentary bones into the mammalian middle ear.

PMID- 30224749
TI  - Structure of the membrane-assembled retromer coat determined by cryo-electron
      tomography.
AB  - Eukaryotic cells traffic proteins and lipids between different compartments using
      protein-coated vesicles and tubules. The retromer complex is required to generate
      cargo-selective tubulovesicular carriers from endosomal membranes1-3. Conserved
      in eukaryotes, retromer controls the cellular localization and homeostasis of
      hundreds of transmembrane proteins, and its disruption is associated with major
      neurodegenerative disorders4-7. How retromer is assembled and how it is recruited
      to form coated tubules is not known. Here we describe the structure of the
      retromer complex (Vps26-Vps29-Vps35) assembled on membrane tubules with the
      bin/amphiphysin/rvs-domain-containing sorting nexin protein Vps5, using cryo
      electron tomography and subtomogram averaging. This reveals a membrane-associated
      Vps5 array, from which arches of retromer extend away from the membrane surface.
      Vps35 forms the 'legs' of these arches, and Vps29 resides at the apex where it is
      free to interact with regulatory factors. The bases of the arches connect to each
      other and to Vps5 through Vps26, and the presence of the same arches on coated
      tubules within cells confirms their functional importance. Vps5 binds to Vps26 at
      a position analogous to the previously described cargo- and Snx3-binding site,
      which suggests the existence of distinct retromer-sorting nexin assemblies. The
      structure provides insight into the architecture of the coat and its mechanism of
      assembly, and suggests that retromer promotes tubule formation by directing the
      distribution of sorting nexin proteins on the membrane surface while providing a
      scaffold for regulatory-protein interactions.

PMID- 30224750
TI  - Addendum: Voxel-based, brain-wide association study of aberrant functional
      connectivity in schizophrenia implicates thalamocortical circuitry.

PMID- 30224751
TI  - Novel Clade C-I Clostridium difficile strains escape diagnostic tests, differ in
      pathogenicity potential and carry toxins on extrachromosomal elements.
AB  - The population structure of Clostridium difficile currently comprises eight major
      genomic clades. For the highly divergent C-I clade, only two toxigenic strains
      have been reported, which lack the tcdA and tcdC genes and carry a complete locus
      for the binary toxin (CDT) next to an atypical TcdB monotoxin pathogenicity locus
      (PaLoc). As part of a routine surveillance of C. difficile in stool samples from
      diarrheic human patients, we discovered three isolates that consistently gave
      negative results in a PCR-based screening for tcdC. Through phenotypic assays,
      whole-genome sequencing, experiments in cell cultures, and infection biomodels we
      show that these three isolates (i) escape common laboratory diagnostic
      procedures, (ii) represent new ribotypes, PFGE-types, and sequence types within
      the Clade C-I, (iii) carry chromosomal or plasmidal TcdBs that induce classical
      or variant cytopathic effects (CPE), and (iv) cause different levels of
      cytotoxicity and hamster mortality rates. These results show that new strains of
      C. difficile can be detected by more refined techniques and raise questions on
      the origin, evolution, and distribution of the toxin loci of C. difficile and the
      mechanisms by which this emerging pathogen causes disease.

PMID- 30224752
TI  - A Supramolecular Approach for Enhanced Antibacterial Activity and Extended Shelf
      life of Fluoroquinolone Drugs with Cucurbit[7]uril.
AB  - The host-guest interactions of a third-generation fluoroquinone, danofloxacin
      (DOFL), with the macrocyclic host cucurbit[7]uril (CB7) have been investigated at
      different pH values (~3.5, 7.5, and 10). The photophysical properties have been
      positively affected, that is, the fluorescence yield and lifetime increased, as
      well as the photostability of DOFL improved in the presence of CB7. The
      antibacterial activity of DOFL is enhanced in the presence of CB7, as tested
      against four pathogenic bacteria; highest activity has been found towards B.
      cereus and E. coli, and lower activity towards S. aureus and S. typhi. The
      antibacterial activity of two additional second-generation fluoroquinones, i.e.,
      norfloxacin and ofloxacin, has also been investigated in the absence as well as
      the presence of CB7 and compared with that of DOFL. In case of all drugs, the
      minimum inhibitory concentration (MIC) was reduced 3-5 fold in the presence of
      CB7. The extended shelf-life (antibacterial activity over time) of the
      fluoroquinone drugs in the presence of CB7, irrespective of four types of
      bacteria, can be attributed to the enhanced photostability of their CB7
      complexes, which can act as better antibiotics with a longer expiry date than
      uncomplexed DOFL.

PMID- 30224753
TI  - Computational measurement of tumor immune microenvironment in gastric
      adenocarcinomas.
AB  - The use of four groups of tumor immune microenvironments (TME) based on PD-L1 and
      tumor-infiltrating T lymphocytes (TIL) is a reliable biomarker for anti-PD-1/PD
      L1 inhibitor therapy. We classified the TME in 241 gastric cancers which were
      subdivided according to 40 EBV+, 76 microsatellite instability-high (MSI-H), and
      125 EBV-/microsatellite-stable (MSS) subtypes by quantitative image analysis
      (QIA) and correlated the results with mRNA expression levels. The mean PD-L1
      ratio and CD8 ratio in EBV+, MSI-H, and EBV-/MSS GCs were significantly different
      (P < 0.006). The PD-L1 ratio and CD8 ratio obtained by QIA correlated well with
      the RNA levels of PD-L1 (r = 0.63) and CD8 (r = 0.67), respectively. The TME were
      type I (PD-L1H/CD8H) in 45, type II (PD-L1L/CD8L) in 106, type III (PD-L1H/CD8L)
      in 8, and type IV (PD-L1L/CD8H) in 82 cases. The type I TME was significantly
      associated with high TIL (P = 3.0E-11) and EBV+ status (P = 8.55E-08). In
      conclusion, QIA results correlated well with the mRNA expression levels and
      classified TME of gastric cancers.

PMID- 30224754
TI  - Correlation of body mass index with serum DDTs predicts lower risk of breast
      cancer before the age of 50: prospective evidence in the Child Health and
      Development Studies.
AB  - Many suspected breast cancer risk factors, including the pesticide
      dichlorodiphenyltrichloroethane (DDT) and its metabolite
      dichlorodiphenyldichloroethylene (DDE), are stored in fat where they could
      influence carcinogenesis. We tested the hypothesis that the relationship of DDT
      and DDE (DDTs) with adiposity is modified by disposition to develop breast
      cancer. We predicted that concentrations of serum DDTs would be inversely
      correlated with body mass index (BMI) during active exposure when DDTs move into
      the larger fat pool. We described this correlation at an average of 17 years
      before breast cancer was diagnosed, in a prospective nested case-control study in
      the Child Health and Development Studies. Women entered the study during
      pregnancy from 1959 to 1966 when DDT was in active use. In total, 133 breast
      cancer cases were diagnosed under the age of 50 as of 1998. Mean time to
      diagnosis was 17 years. In total, 133 controls were matched to cases on birth
      year. We observed the expected inverse correlation of serum DDTs with BMI only in
      women who remained cancer-free and not in women who ultimately developed breast
      cancer (p for interaction < 0.05). Findings suggest that vulnerability to breast
      cancer before the age of 50 may be associated with an uncoupling of the inverse
      correlation between BMI and serum DDTs. Investigation into mechanisms may
      eventually reveal early biomarkers of breast cancer risk.

PMID- 30224756
TI  - BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric
      brain tumors.
AB  - Pediatric brain tumors are highly associated with epileptic seizures1. However,
      their epileptogenic mechanisms remain unclear. Here, we show that the oncogenic
      BRAF somatic mutation p.Val600Glu (V600E) in developing neurons underlies
      intrinsic epileptogenicity in ganglioglioma, one of the leading causes of
      intractable epilepsy2. To do so, we developed a mouse model harboring the
      BRAFV600E somatic mutation during early brain development to reflect the most
      frequent mutation, as well as the origin and timing thereof. Therein, the
      BRAFV600E mutation arising in progenitor cells during brain development led to
      the acquisition of intrinsic epileptogenic properties in neuronal lineage cells,
      whereas tumorigenic properties were attributed to high proliferation of glial
      lineage cells. RNA sequencing analysis of patient brain tissues with the mutation
      revealed that BRAFV600E-induced epileptogenesis is mediated by RE1-silencing
      transcription factor (REST), which is a regulator of ion channels and
      neurotransmitter receptors associated with epilepsy. Moreover, we found that
      seizures in mice were significantly alleviated by an FDA-approved BRAFV600E
      inhibitor, vemurafenib, as well as various genetic inhibitions of Rest.
      Accordingly, this study provides direct evidence of a BRAF somatic mutation
      contributing to the intrinsic epileptogenicity in pediatric brain tumors and
      suggests that BRAF and REST could be treatment targets for intractable epilepsy.

PMID- 30224755
TI  - Neural stem cells deriving from chick embryonic hindbrain recapitulate hindbrain
      development in culture.
AB  - Neural stem cells (NSCs) are self-renewing multipotent cells that line the neural
      tube and generate all the nervous system. Understanding NSC biology is
      fundamental for neurodevelopmental research and therapy. Many studies emphasized
      the need to culture NSCs, which are typically purified from mammalian
      embryonic/adult brains. These sources are somewhat limited in terms of quantity,
      availability and animal ethical guidelines. Therefore, new sources are needed.
      The chick is a powerful system for experimental embryology which contributed
      enormously to neurodevelopmental concepts. Its accessibility, genetic/molecular
      manipulations, and homology to other vertebrates, makes it valuable for
      developmental biology research. Recently, we identified a population of NSCs in
      the chick hindbrain. It resides in rhombomere-boundaries, expresses Sox2 and
      generates progenitors and neurons. Here, we investigated whether these cells can
      recapitulate hindbrain development in culture. By developing approaches to
      propagate and image cells, manipulate their growth-conditions and separate them
      into subpopulations, we demonstrate the ordered formation of multipotent and self
      renewing neurospheres that maintain regional identity and display differential
      stem/differentiation/proliferation properties. Live imaging revealed new cellular
      dynamics in the culture. Collectively, these NSC cultures reproduce major aspects
      of hindbrain development in-vitro, proposing the chick as a model for culturing
      hindbrain-NSCs that can be directly applied to other neural-tube domains and
      species.

PMID- 30224757
TI  - Classification and mutation prediction from non-small cell lung cancer
      histopathology images using deep learning.
AB  - Visual inspection of histopathology slides is one of the main methods used by
      pathologists to assess the stage, type and subtype of lung tumors. Adenocarcinoma
      (LUAD) and squamous cell carcinoma (LUSC) are the most prevalent subtypes of lung
      cancer, and their distinction requires visual inspection by an experienced
      pathologist. In this study, we trained a deep convolutional neural network
      (inception v3) on whole-slide images obtained from The Cancer Genome Atlas to
      accurately and automatically classify them into LUAD, LUSC or normal lung tissue.
      The performance of our method is comparable to that of pathologists, with an
      average area under the curve (AUC) of 0.97. Our model was validated on
      independent datasets of frozen tissues, formalin-fixed paraffin-embedded tissues
      and biopsies. Furthermore, we trained the network to predict the ten most
      commonly mutated genes in LUAD. We found that six of them-STK11, EGFR, FAT1,
      SETBP1, KRAS and TP53-can be predicted from pathology images, with AUCs from
      0.733 to 0.856 as measured on a held-out population. These findings suggest that
      deep-learning models can assist pathologists in the detection of cancer subtype
      or gene mutations. Our approach can be applied to any cancer type, and the code
      is available at https://github.com/ncoudray/DeepPATH .

PMID- 30224759
TI  - LncGata6 maintains stemness of intestinal stem cells and promotes intestinal
      tumorigenesis.
AB  - The intestinal epithelium harbours remarkable self-renewal capacity that is
      driven by Lgr5+ intestinal stem cells (ISCs) at the crypt base. However, the
      molecular mechanism controlling Lgr5+ ISC stemness is incompletely understood. We
      show that a Gata6 long noncoding RNA (lncGata6) is highly expressed in ISCs.
      LncGata6 knockout or conditional knockout in ISCs impairs the stemness of ISCs
      and epithelial regeneration. Mechanistically, lncGata6 recruits the NURF complex
      onto the Ehf promoter to induce its transcription, which promotes the expression
      of Lgr4/5 to enhance Wnt signalling activation. Moreover, the human orthologue
      lncGATA6 is highly expressed in the cancer stem cells of colorectal cancer and
      promotes tumour initiation and progression. Antisense oligonucleotides against
      lncGATA6 exhibit strong therapeutic efficacy on colorectal cancer. Thus,
      targeting lncGATA6 will have potential clinical applications in colorectal cancer
      treatment as an ideal therapeutic target.

PMID- 30224758
TI  - Transcriptional addiction in cancer cells is mediated by YAP/TAZ through BRD4.
AB  - Cancer cells rely on dysregulated gene expression. This establishes specific
      transcriptional addictions that may be therapeutically exploited. Yet, the
      mechanisms that are ultimately responsible for these addictions are poorly
      understood. Here, we investigated the transcriptional dependencies of transformed
      cells to the transcription factors YAP and TAZ. YAP/TAZ physically engage the
      general coactivator bromodomain-containing protein 4 (BRD4), dictating the genome
      wide association of BRD4 to chromatin. YAP/TAZ flag a large set of enhancers with
      super-enhancer-like functional properties. YAP/TAZ-bound enhancers mediate the
      recruitment of BRD4 and RNA polymerase II at YAP/TAZ-regulated promoters,
      boosting the expression of a host of growth-regulating genes. Treatment with
      small-molecule inhibitors of BRD4 blunts YAP/TAZ pro-tumorigenic activity in
      several cell or tissue contexts, causes the regression of pre-established,
      YAP/TAZ-addicted neoplastic lesions and reverts drug resistance. This work sheds
      light on essential mediators, mechanisms and genome-wide regulatory elements that
      are responsible for transcriptional addiction in cancer and lays the groundwork
      for a rational use of BET inhibitors according to YAP/TAZ biology.

PMID- 30224760
TI  - Single particle trajectories reveal active endoplasmic reticulum luminal flow.
AB  - The endoplasmic reticulum (ER), a network of membranous sheets and pipes,
      supports functions encompassing biogenesis of secretory proteins and delivery of
      functional solutes throughout the cell1,2. Molecular mobility through the ER
      network enables these functionalities, but diffusion alone is not sufficient to
      explain luminal transport across supramicrometre distances. Understanding the ER
      structure-function relationship is critical in light of mutations in ER
      morphology-regulating proteins that give rise to neurodegenerative disorders3,4.
      Here, super-resolution microscopy and analysis of single particle trajectories of
      ER luminal proteins revealed that the topological organization of the ER
      correlates with distinct trafficking modes of its luminal content: with a
      dominant diffusive component in tubular junctions and a fast flow component in
      tubules. Particle trajectory orientations resolved over time revealed an
      alternating current of the ER contents, while fast ER super-resolution identified
      energy-dependent tubule contraction events at specific points as a plausible
      mechanism for generating active ER luminal flow. The discovery of active flow in
      the ER has implications for timely ER content distribution throughout the cell,
      particularly important for cells with extensive ER-containing projections such as
      neurons.

PMID- 30224761
TI  - Life, death and autophagy.
AB  - Autophagy influences cell survival through maintenance of cell bioenergetics and
      clearance of protein aggregates and damaged organelles. Several lines of evidence
      indicate that autophagy is a multifaceted regulator of cell death, but
      controversy exists over whether autophagy alone can drive cell death under
      physiologically relevant circumstances. Here, we review the role of autophagy in
      cell death and examine how autophagy interfaces with other forms of cell death
      including apoptosis and necrosis.

PMID- 30224762
TI  - Metabolic control of ferroptosis in cancer.

PMID- 30224763
TI  - Silencing of quinolinic acid phosphoribosyl transferase (QPT) gene for enhanced
      production of scopolamine in hairy root culture of Duboisia leichhardtii.
AB  - Scopolamine is a pharmaceutically important tropane alkaloid which is used
      therapeutically in the form of an anesthetic and antispasmodic drug. The present
      study demonstrates enhanced scopolamine production from transgenic hairy root
      clones of Duboisia leichhardtii wherein the expression of quinolinate
      phosphoribosyl transferase (QPT) gene was silenced using the QPT-RNAi construct
      under the control of CaMV 35 S promoter. The RNAi hairy roots clones viz. P4, P7,
      P8, and P12 showed the enhanced synthesis of scopolamine with significant
      inhibition of nicotine biosynthesis. Optimization of culture duration in
      combination with methyl jasmonate elicitor in different concentrations (50 uM-200
      uM) was carried out. Maximum synthesis of scopolamine had obtained from HR clones
      P7 (8.84 +/- 0.117 mg/gm) on the 30th day of cultivation. Conspicuously,
      elicitation with wound-associated hormone methyl jasmonate enhanced the yield of
      scopolamine 2.2 fold (19.344 +/- 0.275 mg/gm) compared to the culture lacking the
      elicitor. The transgenic hairy roots cultures established with RNAi mediated
      silencing of quinolinate phosphoribosyl transferase gene provides an alternative
      approach to increase the yield of scopolamine in fulfilling the demand of this
      secondary metabolite.

PMID- 30224764
TI  - Effective Radiative Properties of Tilted Metallic Nanorod Arrays Considering
      Polarization Coupling.
AB  - With the advent of new nanomanufacturing techniques has come the rise of the
      field of nanophotonics and an increased need to determine optical properties of
      novel structures. Commercial software packages are able to estimate the behavior,
      but require large resources and heavy computational time. By combining coordinate
      transforms and Effective Medium Theory (EMT), an effective relative permittivity
      tensor is defined and further exploited to calculate the polarization-coupled
      Fresnel coefficients through Maxwell's equations. A uniaxial simplification is
      made to show the case of tilted nanorod arrays. To demonstrate the flexibility of
      this system, the interfacial reflectance has been calculated for both s- and p
      polarizations as well as the coupled case with the volume filling fractions of f
      = 0.10 and 0.30 for silver (Ag) and titanium (Ti) nanorods, and a scenario of a
      Ag nanorod array with polymethyl methacrylate (PMMA) as the surrounding medium.
      The exact results computed by the finite-difference time-domain method justify
      the validity of EMT with polarization coupling taken into account. The effects of
      incidence angle and azimuthal angle on reflectance are also discussed. The
      relatively simple nature of this approach allows for fast estimations of the
      optical properties of various nanostructures.

PMID- 30224765
TI  - Impact of timing of surgery in elderly hip fracture patients: a systematic review
      and meta-analysis.
AB  - We aimed to assess the impact of timing of surgery in elderly patients with acute
      hip fracture on morbidity and mortality. We systematically searched MEDLINE, the
      Cochrane Library, Embase, PubMed, and trial registries from 01/1997 to 05/2017,
      as well as reference lists of relevant reviews, archives of orthopaedic
      conferences, and contacted experts. Eligible studies had to be randomised
      controlled trials (RCTs) or prospective cohort studies, including patients 60
      years or older with acute hip fracture. Two authors independently assessed study
      eligibility, abstracted data, and critically appraised study quality. We
      conducted meta-analyses using the generic inverse variance model. We included 28
      prospective observational studies reporting data of 31,242 patients. Patients
      operated on within 48 hours had a 20% lower risk of dying within 12 months (risk
      ratio (RR) 0.80, 95% confidence interval (CI) 0.66-0.97). No statistical
      significant different mortality risk was observed when comparing patients
      operated on within or after 24 hours (RR 0.82, 95% CI 0.67-1.01). Adjusted data
      demonstrated fewer complications (8% vs. 17%) in patients who had early surgery,
      and increasing risk for pressure ulcers with increased time of delay in another
      study. Early hip surgery within 48 hours was associated with lower mortality risk
      and fewer perioperative complications.

PMID- 30224766
TI  - Multi-terrane structure controls the contrasting lithospheric evolution beneath
      the western and central-eastern Tibetan plateau.
AB  - The Tibetan plateau is manifested by contrasting along-strike lithospheric
      structures, but its formation mechanism and the relationship with the
      heterogeneous multi-terrane configuration is a challenging problem. Here we
      conduct systematic numerical modeling to explore the roles of width, density, and
      rheological properties of the multiple terranes in the lithospheric evolution of
      the Tibetan plateau, which reveals two distinct collision modes. In Mode-I, the
      lithospheric mantles of both the strong and weak terranes in the Tibetan plate
      are completely detached, followed by the underthrusting of Indian lithosphere
      beneath the whole plateau. Alternatively, Mode-II is characterized by full
      detachment of the weak terranes, but (partial) residue of the strong terranes
      during collision. These two contrasting modes, broadly consistent with the
      lithospheric structures of western and central-eastern Tibetan plateau,
      respectively, are strongly dependent on the along-strike variation of the width
      of the strong Lhasa-Qiangtang terranes.

PMID- 30224767
TI  - Maternal and environmental risk factors for neonatal AKI and its long-term
      consequences.
AB  - Acute kidney injury (AKI) is a common and life-threatening complication in
      critically ill neonates. Gestational risk factors for AKI include premature
      birth, intrauterine growth restriction and low birthweight, which are associated
      with poor nephron development and are often the consequence of pre-gestational
      and gestational factors, such as poor nutritional status. Our understanding of
      how to best optimize renal development and prevent AKI is in its infancy;
      however, the identification of pre-gestational and gestational factors that
      increase the risk of adverse neonatal outcomes and the implementation of
      interventions, such as improving nutritional status early in pregnancy, have the
      potential to optimize fetal growth and reduce the risk of preterm birth, thereby
      improving kidney health. The overall risk of AKI among critically ill and
      premature neonates is exacerbated postnatally as these infants are often exposed
      to dehydration, septic shock and potentially nephrotoxic medications. Strategies
      to improve outcomes - for example, through careful evaluation of nephrotoxic
      drugs - may reduce the incidence of AKI and its consequences among this
      population. Management strategies and updated technology that will support
      neonates with AKI are greatly needed. Extremely premature infants and those who
      survive an episode of AKI should be screened for chronic kidney disease until
      early adulthood. Here, we provide an overview of our current understanding of
      neonatal AKI, focusing on its relationship to preterm birth and growth
      restriction. We describe factors that prevent optimal nephrogenesis during
      pregnancy and provide a framework for future explorations designed to maximize
      outcomes in this vulnerable population.

PMID- 30224768
TI  - Serotonin receptor type 1B constitutes a therapeutic target for MDS and CMML.
AB  - Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are
      chronic myeloid clonal neoplasms. To date, the only potentially curative therapy
      for these disorders remains allogeneic hematopoietic progenitor cell
      transplantation (HCT), although patient eligibility is limited due to high
      morbimortality associated with this procedure coupled with advanced age of most
      patients. Dopamine receptors (DRs) and serotonin receptors type 1 (HTR1s) were
      identified as cancer stem cell therapeutic targets in acute myeloid leukemia.
      Given their close pathophysiologic relationship, expression of HTR1s and DRs was
      interrogated in MDS and CMML. Both receptors were differentially expressed in
      patient samples compared to healthy donors. Treatment with HTR1B antagonists
      reduced cell viability. HTR1 antagonists showed a synergistic cytotoxic effect
      with currently approved hypomethylating agents in AML cells. Our results suggest
      that HTR1B constitutes a novel therapeutic target for MDS and CMML. Due to its
      druggability, the clinical development of new regimens based on this target is
      promising.

PMID- 30224770
TI  - T cells home in on brain cancer.

PMID- 30224769
TI  - Enhanced Sensitivity of Patient-Derived Pediatric High-Grade Brain Tumor
      Xenografts to Oncolytic HSV-1 Virotherapy Correlates with Nectin-1 Expression.
AB  - Pediatric high-grade brain tumors and adult glioblastoma are associated with
      significant morbidity and mortality. Oncolytic herpes simplex virus-1 (oHSV) is a
      promising approach to target brain tumors; oHSV G207 and M032 (encodes human
      interleukin-12) are currently in phase I clinical trials in children with
      malignant supratentorial brain tumors and adults with glioblastoma, respectively.
      We sought to compare the sensitivity of patient-derived pediatric malignant brain
      tumor and adult glioblastoma xenografts to these clinically-relevant oHSV. In so
      doing we found that pediatric brain tumors were more sensitive to the viruses and
      expressed significantly more nectin-1 (CD111) than adult glioblastoma. Pediatric
      embryonal and glial tumors were 74-fold and 14-fold more sensitive to M002 and 16
      fold and 6-fold more sensitive to G207 than adult glioblastoma, respectively. Of
      note, pediatric embryonal tumors were more sensitive than glial tumors.
      Differences in sensitivity may be due in part to nectin-1 expression, which
      predicted responses to the viruses. Treatment with oHSV resulted in prolonged
      survival in both pediatric and adult intracranial patient-dervied tumor xenograft
      models. Our results suggest that pediatric brain tumors are ideal targets for
      oHSV and that brain tumor expression of nectin-1 may be a useful biomarker to
      predict patient response to oHSV.

PMID- 30224771
TI  - Epidemiology of Childhood Onset Essential Hypertension.
AB  - The knowledge of epidemiology of a disease is paramount in identifying preventive
      measures. Currently there is a paucity of literature on the epidemiologic
      determinants of childhood onset essential hypertension (EH). We evaluated
      children with EH, ascertained in a rigorous manner, in a large multiethnic
      population in a tertiary pediatric hypertension clinic. We enrolled children with
      and without EH and obtained data by in-person interview of their parents and by
      direct anthropometric measurements including blood pressures. A total of 148
      children (76 hypertension probands, 72 control probands, and males 53%, mean age
      12.2 +/- 4.3 years) were enrolled. Of these 148 children, 51 pairs were matched
      1:1 on ethnicity, gender and age (+/-2.5 years). In this study we evaluated the
      demographics, genetic predisposition and a variety of exposures including,
      socioeconomic, perinatal, lifestyle and environmental, between cases and
      controls. All measures were similar between cases and controls other than a
      significantly higher BMI (p = 0.01) and rates of obesity (p = 0.03), and a
      difference of near-significance in any family history of EH (p = 0.05) higher in
      cases compared to controls. The odds of obesity was 3.5 times higher among cases
      than controls. In this study, we evaluated a variety of prenatal and postnatal
      exposures that could potentially contributed to the EH phenotype in childhood.
      The findings of the study elucidate the epidemiology of EH in children and two
      important associated risk factors, any family history of hypertension and a
      higher body weight.

PMID- 30224772
TI  - Effects of soiling on photovoltaic (PV) modules in the Atacama Desert.
AB  - Soiling by dry deposition affects the power output of photovoltaic (PV) modules,
      especially under dry and arid conditions that favor natural atmospheric aerosols
      (wind-blown dust). In this paper, we report on measurements of the soiling effect
      on the energy yield of grid-connected crystalline silicon PV modules deployed in
      five cities across a north-south transect of approximately 1300 km in the Atacama
      Desert ranging from latitude 18 degrees S to latitude 30 degrees S. Energy losses
      were assessed by comparing side-by-side outputs of four co-planar PV modules. Two
      of the PV modules of the array were kept clean as a control, while we allowed the
      other two to naturally accumulate soiling for 12 months (from January 2017 to
      January 2018). We found that the combination of high deposition rates and
      infrequent rainfalls led to annual energy losses that peaked at 39% in the
      northern coastal part of the desert. In contrast, annual energy losses of 3% or
      less were measured at relatively high-altitude sites and also at locations in the
      southern part of the desert. For comparison, soiling-induced annual energy losses
      of about 7% were measured in Santiago, Chile (33 degrees S), a major city with
      higher rainfall frequency but where urban pollution plays a significant role.

PMID- 30224773
TI  - Interface morphology effect on the spin mixing conductance of Pt/Fe3O4 bilayers.
AB  - Non-magnetic (NM) metals with strong spin-orbit coupling have been recently
      explored as a probe of interface magnetism on ferromagnetic insulators (FMI) by
      means of the spin Hall magnetoresistance (SMR) effect. In NM/FMI
      heterostructures, increasing the spin mixing conductance (SMC) at the interface
      comes as an important step towards devices with maximized SMR. Here we report on
      the study of SMR in Pt/Fe3O4 bilayers at cryogenic temperature, and identify a
      strong dependence of the determined real part of the complex SMC on the interface
      roughness. We tune the roughness of the Pt/Fe3O4 interface by controlling the
      growth conditions of the Fe3O4 films, namely by varying the thickness, growth
      technique, and post-annealing processes. Field-dependent and angular-dependent
      magnetoresistance measurements sustain the clear observation of SMR. The
      determined real part of the complex SMC of the Pt/Fe3O4 bilayers ranges from 4.96
      * 1014 Omega-1 m-2 to 7.16 * 1014 Omega-1 m-2 and increases with the roughness of
      the Fe3O4 underlayer. We demonstrate experimentally that the interface
      morphology, acting as an effective interlayer potential, leads to an enhancement
      of the spin mixing conductance.

PMID- 30224775
TI  - 18F-Fluciclovine-PET-CT LOCATEs recurrence.

PMID- 30224774
TI  - Adolescent cannabinoid exposure induces irritability-like behavior and cocaine
      cross-sensitization without affecting the escalation of cocaine self
      administration in adulthood.
AB  - Cannabis use is typically initiated during adolescence and is a significant risk
      factor for the development of cocaine use in adulthood. However, no preclinical
      studies have examined the effects of adolescent cannabinoid exposure on cocaine
      dependence in adulthood using the escalation model of cocaine self-administration
      and the assessment of negative emotional states. In the present study, we found
      that exposure to the cannabinoid receptor agonist WIN55,212-2 (WIN) in
      adolescence produced irritability-like behavior and psychomotor cross
      sensitization to cocaine in adolescence. In adulthood, rats were allowed to self
      administer cocaine. The acquisition of cocaine self-administration was lower in
      rats with adolescent WIN exposure compared with controls. However, both WIN
      exposed and control rats escalated their cocaine intake at the same rate, had
      similar responding under a progressive-ratio schedule of reinforcement, and had
      similar psychomotor responses to cocaine. Interestingly, the increase in
      irritability-like behavior that was previously observed in adolescence after WIN
      exposure persisted into adulthood. Whether the persisting increase in
      irritability-like behavior after WIN exposure has translational relevance remains
      to be studied. In summary, these results suggest that psychoactive cannabinoid
      exposure during adolescence is unlikely to have a major effect on the escalation
      of cocaine intake or the development of compulsive-like responding per se in
      adulthood in a rat model of cocaine self-administration. However, whether the
      persisting irritability-like behavior may predispose an individual to mood
      related impairments in adulthood or predict such impairments warrants further
      investigation.

PMID- 30224776
TI  - CXCR4-HIF-1alpha interaction drives metastasis.

PMID- 30224777
TI  - Interfocal genomic heterogeneity uncovered.

PMID- 30224778
TI  - Immunogenomic landscape of dMMR tumours.

PMID- 30224779
TI  - Super-resolution ultrasound imaging method for microvasculature in vivo with a
      high temporal accuracy.
AB  - Traditional ultrasound imaging techniques are limited in spatial resolution to
      visualize angiogenic vasa vasorum that is considered as an important marker for
      atherosclerotic plaque progression and vulnerability. The recently introduced
      super-resolution imaging technique based on microbubble center localization has
      shown potential to achieve unprecedented high spatial resolution beyond the
      acoustic diffraction limit. However, a major drawback of the current super
      resolution imaging approach is low temporal resolution because it requires a
      large number of imaging frames. In this study, a new imaging sequence and signal
      processing approach for super-resolution ultrasound imaging are presented to
      improve temporal resolution by employing deconvolution and spatio-temporal
      interframe-correlation based data acquisition. In vivo feasibility of the
      developed technology is demonstrated and evaluated in imaging vasa vasorum in the
      rabbit atherosclerosis model. The proposed method not only identifies a tiny
      vessel with a diameter of 41 MUm, 5 times higher spatial resolution than the
      acoustic diffraction limit at 7.7 MHz, but also significantly improves temporal
      resolution that allows for imaging vessels over cardiac motion.

PMID- 30224780
TI  - Spatial separation of catches in highly mixed fisheries.
AB  - Mixed fisheries are the dominant type of fishery worldwide. Overexploitation in
      mixed fisheries occurs when catches continue for available quota species while
      low quota species are discarded. As EU fisheries management moves to count all
      fish caught against quota (the "landing obligation"), the challenge is to catch
      available quota within new constraints, else lose productivity. A mechanism for
      decoupling exploitation of species caught together is spatial targeting, which
      remains challenging due to complex fishery and population dynamics. How far
      spatial targeting can go to practically separate species is often unknown and
      anecdotal. We develop a dimension-reduction framework based on joint dynamic
      species distribution modelling to understand how spatial community and fishery
      dynamics interact to determine species and size composition. In application to
      the highly mixed fisheries of the Celtic Sea, clear common spatial patterns
      emerge for three distinct assemblages. While distribution varies interannually,
      the same species are consistently found in higher densities together, with more
      subtle differences within assemblages, where spatial separation may not be
      practically possible. We highlight the importance of dimension reduction
      techniques to focus management discussion on axes of maximal separation and
      identify spatiotemporal modelling as a scientific necessity to address the
      challenges of managing mixed fisheries.

PMID- 30224781
TI  - The 40Ar/39Ar dating of quartz: new insights into the metallogenic chronology of
      the Jinchang gold deposit and its geological significance.
AB  - The Jinchang gold deposit has been extensively studied, but precise dates for its
      formation are debated. Native gold mainly occurs as inclusions within pyrite and
      quartz. In this study, we analysed quartz crystals coeval with gold precipitation
      from two different types of mineralization using the ArgusVI multi-collector
      noble gas mass spectrometer by the stepwise crushing technique to resolve the
      timing and genesis of gold mineralization. 40Ar/39Ar dating of quartz samples
      (J12Q) from breccia ore yields a plateau age of 109.87 +/- 0.86 Ma, and an
      inverse isochron age of 109.87 +/- 0.88 Ma. Quartz samples (J18Q) from vein ore
      yields a slightly younger plateau age of 107.76 +/- 0.85 Ma, with an inverse
      isochron age of 107.76 +/- 0.92 Ma. These dates place the ore-forming age of the
      Jinchang gold deposit at 107~110 Ma, much younger than previously published
      radiometric ages, suggesting the gold mineralization is spatio-temporally
      associated with the granite porphyry. The formation of the Jinchang gold deposit
      is consistent with the regional late Mesozoic porphyry-epithermal gold
      mineralization event in the Yanbian-Dongning area. Finally, our study shows that
      40Ar/39Ar of quartz can be used as a powerful tool to date the formation ages of
      hydrothermal ore deposits.

PMID- 30224782
TI  - 4pi-periodic Andreev bound states in a Dirac semimetal.
AB  - Although signatures of superconductivity in Dirac semimetals have been reported,
      for instance by applying pressure or using point contacts, our understanding of
      the topological aspects of Dirac semimetal superconductivity is still developing.
      Here, we utilize nanoscale phase-sensitive junction technology to induce
      superconductivity in the Dirac semimetal Bi1-xSbx. Our radiofrequency irradiation
      experiments then reveal a significant contribution of 4pi-periodic Andreev bound
      states to the supercurrent in Nb-Bi0.97Sb0.03-Nb Josephson junctions. The
      conditions for a substantial 4pi contribution to the supercurrent are favourable
      because of the Dirac cone's very broad transmission resonances and a measurement
      frequency faster than the quasiparticle poisoning rate. In addition, we show that
      a magnetic field applied in the plane of the junction allows tuning of the
      Josephson junctions from 0 to pi regimes. Our results open the technologically
      appealing avenue of employing the topological bulk properties of Dirac semimetals
      for topological superconductivity research and topological quantum computer
      development.

PMID- 30224783
TI  - Fluid-enhanced surface diffusion controls intraparticle phase transformations.
AB  - Phase transformations driven by compositional change require mass flux across a
      phase boundary. In some anisotropic solids, however, the phase boundary moves
      along a non-conductive crystallographic direction. One such material is LiXFePO4,
      an electrode for lithium-ion batteries. With poor bulk ionic transport along the
      direction of phase separation, it is unclear how lithium migrates during phase
      transformations. Here, we show that lithium migrates along the solid/liquid
      interface without leaving the particle, whereby charge carriers do not cross the
      double layer. X-ray diffraction and microscopy experiments as well as ab initio
      molecular dynamics simulations show that organic solvent and water molecules
      promote this surface ion diffusion, effectively rendering LiXFePO4 a three
      dimensional lithium-ion conductor. Phase-field simulations capture the effects of
      surface diffusion on phase transformation. Lowering surface diffusivity is
      crucial towards supressing phase separation. This work establishes fluid-enhanced
      surface diffusion as a key dial for tuning phase transformation in anisotropic
      solids.

PMID- 30224784
TI  - A missing step is a key step.

PMID- 30224785
TI  - The mechanism of the ultrafast crystal growth of pure metals from their melts.
AB  - Pure metals can have ultrafast growth rates from their melts, such as a crystal
      of pure nickel that grows at a rate reaching 70 m s-1. These extraordinary growth
      rates suggest that metallic crystals might provide the next generation of phase
      change materials. The huge crystal growth rates of metals are the consequence of
      kinetics without activated control, in sharp contrast to the prediction of the
      'classic' theory of crystal growth. While the existence of barrierless growth
      kinetics is now well established in atomic melts, the physical explanation for
      the absence of an activation barrier to ordering remains unclear. It is something
      of a paradox that diffusion in the liquid metal is governed by thermal activation
      while the movement of the same atoms organizing into a crystal is not. Here we
      use computer simulations of crystallization in pure metals to explicitly resolve
      the origin of the barrierless growth kinetics.

PMID- 30224786
TI  - ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian
      failure.
AB  - PURPOSE: Primary ovarian insufficiency (POI) is a frequent disorder that affects
      ~1% of women under 40 years of age. POI, which is characterized by the premature
      depletion of ovarian follicles and elevated plasma levels of follicle-stimulating
      hormone (FSH), leads to infertility. Although various etiological factors have
      been described, including chromosomal abnormalities and gene variants, most cases
      remain idiopathic. The aim of the present study was to identify and validate
      functionally new sequence variants in ATG (autophagy-related genes) leading to
      POI. METHODS: We have reanalyzed, in silico, the exome sequencing data from a
      previously reported work performed in 69 unrelated POI women. Functional
      experiments using a classical hallmark of autophagy, the microtubule-associated
      protein 1 light chain 3beta (LC3), were then used to link these genes to this
      lysosomal degradation pathway. RESULTS: We venture a functional link between ATG7
      and ATG9A variants and POI. We demonstrated that variant ATG7 and ATG9A led to a
      decrease in autophagosome biosynthesis and consequently to an impairment of
      autophagy, a key biological process implicated in the preservation of the
      primordial follicles forming the ovarian reserve. CONCLUSION: Our results unveil
      that impaired autophagy is a novel pathophysiological mechanism involved in human
      POI.

PMID- 30224787
TI  - Tailoring of low grade coal to fluorescent nanocarbon structures and their
      potential as a glucose sensor.
AB  - Lignite is an abundantly utilized feedstock for the facile synthesis of
      fluorescent carbon dots and carbon nanomaterials. Its value is appreciated as an
      energy source for combustion for long time. Herein we report a novel top-down
      strategy to synthesis lignite based fluorescent nano carbon structures by
      combined acidic oxidation and chemical reflux. The nanocarbon crystallites in
      lignite are converted to oxygenated nano carbon dots and graphene sheets. They
      exhibited stable fluorescence property in the visible region depending on their
      size, functionalities and defects which were highly stable in all the pH
      conditions. These nanocarbon structures are an effective probe for fluorescent
      sensing of label-free and selective detection of glucose ions with detection
      limit as low as 0.125 mM, promising real-world sensor applications. These
      findings establish a scalable method for the production of fluorescent carbon
      based glucose sensor from lignite.

PMID- 30224788
TI  - A new approach to obtain pure and active proteins from Lactococcus lactis protein
      aggregates.
AB  - The production of pure and soluble proteins is a complex, protein-dependent and
      time-consuming process, in particular for those prone-to-aggregate and/or
      difficult-to-purify. Although Escherichia coli is widely used for protein
      production, recombinant products must be co-purified through costly processes to
      remove lipopolysaccharide (LPS) and minimize adverse effects in the target
      organism. Interestingly, Lactococcus lactis, which does not contain LPS, could be
      a promising alternative for the production of relevant proteins. However, to
      date, there is no universal strategy to produce and purify any recombinant
      protein, being still a protein-specific process. In this context and considering
      that L. lactis is also able to form functional protein aggregates under
      overproduction conditions, we explored the use of these aggregates as an
      alternative source of soluble proteins. In this study, we developed a widely
      applicable and economically affordable protocol to extract functional proteins
      from these nanoclusters. For that, two model proteins were used: mammary serum
      amyloid A3 (M-SAA3) and metalloproteinase 9 (MMP-9), a difficult-to-purify and a
      prone-to-aggregate protein, respectively. The results show that it is possible to
      obtain highly pure, soluble, LPS-free and active recombinant proteins from L.
      lactis aggregates through a cost-effective and simple protocol with special
      relevance for difficult-to-purify or highly aggregated proteins.

PMID- 30224789
TI  - Origin of extremely large magnetoresistance in the candidate type-II Weyl
      semimetal MoTe2-x.
AB  - The recent observation of extremely large magnetoresistance (MR) in the
      transition-metal dichalcogenide MoTe2 has attracted considerable interest due to
      its potential technological applications as well as its relationship with novel
      electronic states predicted for a candidate type-II Weyl semimetal. In order to
      understand the origin of the MR, the electronic structure of MoTe2-x (x = 0.08)
      is systematically tuned by application of pressure and probed via its Hall and
      longitudinal conductivities. With increasing pressure, a monoclinic-to
      orthorhombic (1 T' to Td) structural phase transition temperature (T*) gradually
      decreases from 210 K at 1 bar to 58 K at 1.1 GPa, and there is no anomaly
      associated with the phase transition at 1.4 GPa, indicating that a T = 0 K
      quantum phase transition occurs at a critical pressure (Pc) between 1.1 and 1.4
      GPa. The large MR observed at 1 bar is suppressed with increasing pressure and is
      almost saturated at 100% for P > Pc. The dependence on magnetic field of the Hall
      and longitudinal conductivities of MoTe2-x shows that a pair of electron and hole
      bands are important in the low-pressure Td phase, while another pair of electron
      and hole bands are additionally required in the high-pressure 1 T' phase. The MR
      peaks at a characteristic hole-to-electron concentration ratio (nc) and is
      sharply suppressed when the ratio deviates from nc within the Td phase. These
      results establish the comprehensive temperature-pressure phase diagram of MoTe2-x
      and underscore that its MR originates from balanced electron-hole carrier
      concentrations.

PMID- 30224790
TI  - Hydrogen spillover through Matryoshka-type (ZIFs@)n-1ZIFs nanocubes.
AB  - Hydrogen spillover phenomenon is well-documented in hydrogenation catalysis but
      still highly disputed in hydrogen storage. Until now, the existence of hydrogen
      spillover through metal-organic frameworks (MOFs) remains a topic of ongoing
      debate and how far the split hydrogen atoms diffuse in such materials is unknown.
      Herein we provide experimental evidence of the occurrence of hydrogen spillover
      in microporous MOFs at elevated temperatures, and the penetration depths of
      atomic hydrogen were measured quantitatively. We have made Matryoshka-type
      (ZIFs@)n-1ZIFs (where ZIFs = ZIF-8 or ZIF-67) nanocubes, together with Pt
      nanoparticles loaded on their external surfaces to produce atomic hydrogen.
      Within the (ZIFs@)n-1ZIFs, the ZIF-8 shell served as a ruler to measure the
      travelling distance of H atoms while the ZIF-67 core as a terminator of H atoms.
      In addition to the hydrogenolysis at normal pressure, CO2 hydrogenation can also
      trace the migration of H atoms over the ZIF-8 at high pressure.

PMID- 30224791
TI  - Habitual tool use innovated by free-living New Zealand kea.
AB  - The emergence of flexible tool use is rare in the animal kingdom and thought to
      be largely constrained by either cognitive ability or ecological factors. That
      mostly birds with a high level of intelligence innovate tool use in captivity is
      consistent with the former hypothesis. We report here the first documented case
      of habitual tool use innovated in the wild by a bird species only known to have
      used tools in captivity. Trap-boxes containing food-bait and snap-trap(s) were
      installed in the remote Murchison Mountains, New Zealand, from 2002 to catch
      introduced stoats. Kea tampered with the trap-boxes in various ways. Over
      approximately 2.5 years, sticks were found inserted into at least 227 different
      trap-boxes that were up to 27 km apart. Video footage confirmed that the stick
      insertion was kea tool use. Trap-boxes are unlikely to have provided the only
      possibility for kea tool use in their habitat given their extractive foraging and
      skilled object manipulation. We argue that they instead greatly facilitated the
      opportunity for tool use, thus increasing the chance that kea would invent the
      behaviour. The innovation of tool use by kea in response to facilitation provides
      rare field support for the cognitive constraints hypothesis.

PMID- 30224792
TI  - Magnetic domain walls as broadband spin wave and elastic magnetisation wave
      emitters.
AB  - We report on the direct observation of spin wave and elastic wave emission from
      magnetic domain walls in ferromagnetic thin films. Driven by alternating
      homogeneous magnetic fields the magnetic domain walls act as coherent
      magnetisation wave sources. Directional and low damped elastic waves below and
      above the ferromagnetic resonance are excited. The wave vector of the
      magnetoelastically induced acoustic waves is tuned by varying the excitation
      frequency. The occurrence of elastic wave emission is proved by a combination of
      micromagnetic and mechanical finite element simulations. Domain wall emitted
      magnetostatic surface spin waves occur at higher frequencies, which
      characteristics are confirmed by micromagnetic simulations. The distinct modes of
      magnetisation wave excitation from micromagnetic objects are a general physical
      phenomenon relevant for dynamic magnetisation processes in structured magnetic
      films. Magnetic domain walls can act as reconfigurable antennas for spin wave and
      elastic wave generation. The wave orientation can be controlled separately via
      the domain wall orientation for elastic waves and via magnetization orientation
      for magnetostatic surface spin waves.

PMID- 30224793
TI  - Model organism data evolving in support of translational medicine.
AB  - Model organism databases (MODs) have been collecting and integrating biomedical
      research data for 30 years and were designed to meet specific needs of each model
      organism research community. The contributions of model organism research to
      understanding biological systems would be hard to overstate. Modern molecular
      biology methods and cost reductions in nucleotide sequencing have opened avenues
      for direct application of model organism research to elucidating mechanisms of
      human diseases. Thus, the mandate for model organism research and databases has
      now grown to include facilitating use of these data in translational
      applications. Challenges in meeting this opportunity include the distribution of
      research data across many databases and websites, a lack of data format standards
      for some data types, and sustainability of scale and cost for genomic database
      resources like MODs. The issues of widely distributed data and application of
      data standards are some of the challenges addressed by FAIR (Findable,
      Accessible, Interoperable, and Re-usable) data principles. The Alliance of Genome
      Resources is now moving to address these challenges by bringing together expertly
      curated research data from fly, mouse, rat, worm, yeast, zebrafish, and the Gene
      Ontology consortium. Centralized multi-species data access, integration, and
      format standardization will lower the data utilization barrier in comparative
      genomics and translational applications and will provide a framework in which
      sustainable scale and cost can be addressed. This article presents a brief
      historical perspective on how the Alliance model organisms are complementary and
      how they have already contributed to understanding the etiology of human
      diseases. In addition, we discuss four challenges for using data from MODs in
      translational applications and how the Alliance is working to address them, in
      part by applying FAIR data principles. Ultimately, combined data from these
      animal models are more powerful than the sum of the parts.

PMID- 30224794
TI  - Mechanically controlled quantum interference in graphene break junctions.
AB  - The ability to detect and distinguish quantum interference signatures is
      important for both fundamental research and for the realization of devices such
      as electron resonators1, interferometers2 and interference-based spin filters3.
      Consistent with the principles of subwavelength optics, the wave nature of
      electrons can give rise to various types of interference effects4, such as Fabry
      Perot resonances5, Fano resonances6 and the Aharonov-Bohm effect7. Quantum
      interference conductance oscillations8 have, indeed, been predicted for multiwall
      carbon nanotube shuttles and telescopes, and arise from atomic-scale
      displacements between the inner and outer tubes9,10. Previous theoretical work on
      graphene bilayers indicates that these systems may display similar interference
      features as a function of the relative position of the two sheets11,12.
      Experimental verification is, however, still lacking. Graphene nanoconstrictions
      represent an ideal model system to study quantum transport phenomena13-15 due to
      the electronic coherence16 and the transverse confinement of the carriers17.
      Here, we demonstrate the fabrication of bowtie-shaped nanoconstrictions with
      mechanically controlled break junctions made from a single layer of graphene.
      Their electrical conductance displays pronounced oscillations at room
      temperature, with amplitudes that modulate over an order of magnitude as a
      function of subnanometre displacements. Surprisingly, the oscillations exhibit a
      period larger than the graphene lattice constant. Charge-transport calculations
      show that the periodicity originates from a combination of the quantum
      interference and lattice commensuration effects of two graphene layers that slide
      across each other. Our results provide direct experimental observation of a Fabry
      Perot-like interference of electron waves that are partially reflected and/or
      transmitted at the edges of the graphene bilayer overlap region.

PMID- 30224795
TI  - Fast current-driven domain walls and small skyrmions in a compensated
      ferrimagnet.
AB  - Spintronics is a research field that aims to understand and control spins on the
      nanoscale and should enable next-generation data storage and manipulation. One
      technological and scientific key challenge is to stabilize small spin textures
      and to move them efficiently with high velocities. For a long time, research
      focused on ferromagnetic materials, but ferromagnets show fundamental limits for
      speed and size. Here, we circumvent these limits using compensated ferrimagnets.
      Using ferrimagnetic Pt/Gd44Co56/TaOx films with a sizeable Dzyaloshinskii-Moriya
      interaction, we realize a current-driven domain wall motion with a speed of 1.3
      km s-1 near the angular momentum compensation temperature (TA) and room
      temperature-stable skyrmions with minimum diameters close to 10 nm near the
      magnetic compensation temperature (TM). Both the size and dynamics of the
      ferrimagnet are in excellent agreement with a simplified effective ferromagnet
      theory. Our work shows that high-speed, high-density spintronics devices based on
      current-driven spin textures can be realized using materials in which TA and TM
      are close together.

PMID- 30224796
TI  - Energy consumption in chemical fuel-driven self-assembly.
AB  - Nature extensively exploits high-energy transient self-assembly structures that
      are able to perform work through a dissipative process. Often, self-assembly
      relies on the use of molecules as fuel that is consumed to drive
      thermodynamically unfavourable reactions away from equilibrium. Implementing this
      kind of non-equilibrium self-assembly process in synthetic systems is bound to
      profoundly impact the fields of chemistry, materials science and synthetic
      biology, leading to innovative dissipative structures able to convert and store
      chemical energy. Yet, despite increasing efforts, the basic principles underlying
      chemical fuel-driven dissipative self-assembly are often overlooked, generating
      confusion around the meaning and definition of scientific terms, which does not
      favour progress in the field. The scope of this Perspective is to bring closer
      together current experimental approaches and conceptual frameworks. From our
      analysis it also emerges that chemically fuelled dissipative processes may have
      played a crucial role in evolutionary processes.

PMID- 30224797
TI  - Regional Differences in mRNA and lncRNA Expression Profiles in Non-Failing Human
      Atria and Ventricles.
AB  - The four chambers of the human heart play distinct roles in the maintenance of
      normal cardiac function, and are differentially affected by inherited/acquired
      cardiovascular disease. To probe the molecular determinants of these functional
      differences, we examined mRNA and lncRNA expression profiles in the left (LA) and
      right (RA) atria, the left (LV) and right (RV) ventricles, and the
      interventricular septum (IVS) of non-failing human hearts (N = 8). Analysis of
      paired atrial and ventricular samples (n = 40) identified 5,747 mRNAs and 2,794
      lncRNAs that were differentially (>1.5 fold; FDR < 0.05) expressed. The largest
      differences were observed in comparisons between the atrial (RA/LA) and
      ventricular (RV/LV/IVS) samples. In every case (e.g., LA vs LV, LA vs RV, etc.),
      >2,300 mRNAs and >1,200 lncRNAs, corresponding to 17-28% of the total
      transcripts, were differentially expressed. Heterogeneities in mRNA/lncRNA
      expression profiles in the LA and RA, as well as in the LV, RV and IVS, were also
      revealed, although the numbers of differentially expressed transcripts were
      substantially smaller. Gender differences in mRNA and lncRNA expression profiles
      were also evident in non-failing human atria and ventricles. Gene ontology
      classification of differentially expressed gene sets revealed chamber-specific
      enrichment of numerous signaling pathways.

PMID- 30224798
TI  - Structural basis of the arbitrium peptide-AimR communication system in the phage
      lysis-lysogeny decision.
AB  - A bacteriophage can replicate and release virions from a host cell in the lytic
      cycle or switch to a lysogenic process in which the phage integrates itself into
      the host genome as a prophage. In Bacillus cells, some types of phages employ the
      arbitrium communication system, which contains an arbitrium hexapeptide, the
      cellular receptor AimR and the lysogenic negative regulator AimX. This system
      controls the decision between the lytic and lysogenic cycles. However, both the
      mechanism of molecular recognition between the arbitrium peptide and AimR and how
      downstream gene expression is regulated remain unknown. Here, we report crystal
      structures for AimR from the SPbeta phage in the apo form and the arbitrium
      peptide-bound form at 2.20 A and 1.92 A, respectively. With or without the
      peptide, AimR dimerizes through the C-terminal capping helix. AimR assembles a
      superhelical fold and accommodates the peptide encircled by its tetratricopeptide
      repeats, which is reminiscent of RRNPP family members from the quorum-sensing
      system. In the absence of the arbitrium peptide, AimR targets the upstream
      sequence of the aimX gene; its DNA binding activity is prevented following
      peptide binding. In summary, our findings provide a structural basis for peptide
      recognition in the phage lysis-lysogeny decision communication system.

PMID- 30224799
TI  - Salmonella stimulates pro-inflammatory signalling through p21-activated kinases
      bypassing innate immune receptors.
AB  - Microbial infections are most often countered by inflammatory responses that are
      initiated through the recognition of conserved microbial products by innate
      immune receptors and result in pathogen expulsion1-6. However, inflammation can
      also lead to pathology. Tissues such as the intestinal epithelium, which are
      exposed to microbial products, are therefore subject to stringent negative
      regulatory mechanisms to prevent signalling through innate immune receptors6-11.
      This presents a challenge to the enteric pathogen Salmonella Typhimurium, which
      requires intestinal inflammation to compete against the resident microbiota and
      to acquire the nutrients and electron acceptors that sustain its
      replication12,13. We show here that S. Typhimurium stimulates pro-inflammatory
      signalling by a unique mechanism initiated by effector proteins that are
      delivered by its type III protein secretion system. These effectors activate
      Cdc42 and the p21-activated kinase 1 (PAK1) leading to the recruitment of TNF
      receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase
      kinase 7 (TAK1), and the stimulation of nuclear factor kappa-light-chain-enhancer
      of activated B cells (NF-kappaB) inflammatory signalling. The removal of Cdc42,
      PAK1, TRAF6 or TAK1 prevented S. Typhimurium from stimulating NF-kappaB
      signalling in cultured cells. In addition, oral administration of a highly
      specific PAK inhibitor blocked Salmonella-induced intestinal inflammation and
      bacterial replication in the mouse intestine, although it resulted in a
      significant increase in the bacterial loads in systemic tissues. Thus, S.
      Typhimurium stimulates inflammatory signalling in the intestinal tract by
      engaging critical downstream signalling components of innate immune receptors.
      These findings illustrate the unique balance that emerges from host-pathogen co
      evolution, in that pathogen-initiated responses that help pathogen replication
      are also important to prevent pathogen spread to deeper tissues.

PMID- 30224800
TI  - Mini viral RNAs act as innate immune agonists during influenza virus infection.
AB  - The molecular processes that determine the outcome of influenza virus infection
      in humans are multifactorial and involve a complex interplay between host, viral
      and bacterial factors1. However, it is generally accepted that a strong innate
      immune dysregulation known as 'cytokine storm' contributes to the pathology of
      infections with the 1918 H1N1 pandemic or the highly pathogenic avian influenza
      viruses of the H5N1 subtype2-4. The RNA sensor retinoic acid-inducible gene I
      (RIG-I) plays an important role in sensing viral infection and initiating a
      signalling cascade that leads to interferon expression5. Here, we show that short
      aberrant RNAs (mini viral RNAs (mvRNAs)), produced by the viral RNA polymerase
      during the replication of the viral RNA genome, bind to and activate RIG-I and
      lead to the expression of interferon-beta. We find that erroneous polymerase
      activity, dysregulation of viral RNA replication or the presence of avian
      specific amino acids underlie mvRNA generation and cytokine expression in
      mammalian cells. By deep sequencing RNA samples from the lungs of ferrets
      infected with influenza viruses, we show that mvRNAs are generated during
      infection in vivo. We propose that mvRNAs act as the main agonists of RIG-I
      during influenza virus infection.

PMID- 30224801
TI  - A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks
      flavivirus replication.
AB  - The endoplasmic reticulum (ER) is an architecturally diverse organelle that
      serves as a membrane source for the replication of multiple viruses.
      Flaviviruses, including yellow fever virus, West Nile virus, dengue virus and
      Zika virus, induce unique single-membrane ER invaginations that house the viral
      replication machinery1. Whether this virus-induced ER remodelling is vulnerable
      to antiviral pathways is unknown. Here, we show that flavivirus replication at
      the ER is targeted by the interferon (IFN) response. Through genome-scale CRISPR
      screening, we uncovered an antiviral mechanism mediated by a functional gene
      pairing between IFI6 (encoding IFN-alpha-inducible protein 6), an IFN-stimulated
      gene cloned over 30 years ago2, and HSPA5, which encodes the ER-resident heat
      shock protein 70 chaperone BiP. We reveal that IFI6 is an ER-localized integral
      membrane effector that is stabilized through interactions with BiP.
      Mechanistically, IFI6 prophylactically protects uninfected cells by preventing
      the formation of virus-induced ER membrane invaginations. Notably, IFI6 has
      little effect on other mammalian RNA viruses, including the related Flaviviridae
      family member hepatitis C virus, which replicates in double-membrane vesicles
      that protrude outwards from the ER. These findings support a model in which the
      IFN response is armed with a membrane-targeted effector that discriminately
      blocks the establishment of virus-specific ER microenvironments that are required
      for replication.

PMID- 30224803
TI  - Neural implementation of Bayesian inference in a sensorimotor behavior.
AB  - Actions are guided by a Bayesian-like interaction between priors based on
      experience and current sensory evidence. Here we unveil a complete neural
      implementation of Bayesian-like behavior, including adaptation of a prior. We
      recorded the spiking of single neurons in the smooth eye-movement region of the
      frontal eye fields (FEFSEM), a region that is causally involved in smooth-pursuit
      eye movements. Monkeys tracked moving targets in contexts that set different
      priors for target speed. Before the onset of target motion, preparatory activity
      encodes and adapts in parallel with the behavioral adaptation of the prior.
      During the initiation of pursuit, FEFSEM output encodes a maximum a posteriori
      estimate of target speed based on a reliability-weighted combination of the prior
      and sensory evidence. FEFSEM responses during pursuit are sufficient both to
      adapt a prior that may be stored in FEFSEM and, through known downstream
      pathways, to cause Bayesian-like behavior in pursuit.

PMID- 30224802
TI  - Mycobacterium tuberculosis carrying a rifampicin drug resistance mutation
      reprograms macrophage metabolism through cell wall lipid changes.
AB  - Tuberculosis is a significant global health threat, with one-third of the world's
      population infected with its causative agent Mycobacterium tuberculosis (Mtb).
      The emergence of multidrug-resistant (MDR) Mtb that is resistant to the frontline
      anti-tubercular drugs rifampicin and isoniazid forces treatment with toxic second
      line drugs. Currently, ~4% of new and ~21% of previously treated tuberculosis
      cases are either rifampicin-drug-resistant or MDR Mtb infections1. The specific
      molecular host-pathogen interactions mediating the rapid worldwide spread of MDR
      Mtb strains remain poorly understood. W-Beijing Mtb strains are highly prevalent
      throughout the world and associated with increased drug resistance2. In the early
      1990s, closely related MDR W-Beijing Mtb strains (W strains) were identified in
      large institutional outbreaks in New York City and caused high mortality rates3.
      The production of interleukin-1beta (IL-1beta) by macrophages coincides with the
      shift towards aerobic glycolysis, a metabolic process that mediates protection
      against drug-susceptible Mtb4. Here, using a collection of MDR W-Mtb strains, we
      demonstrate that the overexpression of Mtb cell wall lipids, phthiocerol
      dimycocerosates, bypasses the interleukin 1 receptor, type I (IL-1R1) signalling
      pathway, instead driving the induction of interferon-beta (IFN-beta) to reprogram
      macrophage metabolism. Importantly, Mtb carrying a drug resistance-conferring
      single nucleotide polymorphism in rpoB (H445Y)5 can modulate host macrophage
      metabolic reprogramming. These findings transform our mechanistic understanding
      of how emerging MDR Mtb strains may acquire drug resistance single nucleotide
      polymorphisms, thereby altering Mtb surface lipid expression and modulating host
      macrophage metabolic reprogramming.

PMID- 30224804
TI  - Restoring wild-type-like CA1 network dynamics and behavior during adulthood in a
      mouse model of schizophrenia.
AB  - Schizophrenia is a severely debilitating neurodevelopmental disorder.
      Establishing a causal link between circuit dysfunction and particular behavioral
      traits that are relevant to schizophrenia is crucial to shed new light on the
      mechanisms underlying the pathology. We studied an animal model of the human
      22q11 deletion syndrome, the mutation that represents the highest genetic risk of
      developing schizophrenia. We observed a desynchronization of hippocampal neuronal
      assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing
      parvalbumin interneuron excitability with pharmacological or chemogenetic
      approaches was sufficient to restore wild-type-like CA1 network dynamics and
      hippocampal-dependent behavior during adulthood. In conclusion, our data provide
      insights into the network dysfunction underlying schizophrenia and highlight the
      use of reverse engineering to restore physiological and behavioral phenotypes in
      an animal model of neurodevelopmental disorder.

PMID- 30224805
TI  - Coordinated cerebellar climbing fiber activity signals learned sensorimotor
      predictions.
AB  - The prevailing model of cerebellar learning states that climbing fibers (CFs) are
      both driven by, and serve to correct, erroneous motor output. However, this model
      is grounded largely in studies of behaviors that utilize hardwired neural
      pathways to link sensory input to motor output. To test whether this model
      applies to more flexible learning regimes that require arbitrary sensorimotor
      associations, we developed a cerebellar-dependent motor learning task that is
      compatible with both mesoscale and single-dendrite-resolution calcium imaging in
      mice. We found that CFs were preferentially driven by and more time-locked to
      correctly executed movements and other task parameters that predict reward
      outcome, exhibiting widespread correlated activity in parasagittal processing
      zones that was governed by these predictions. Together, our data suggest that
      such CF activity patterns are well-suited to drive learning by providing
      predictive instructional input that is consistent with an unsigned reinforcement
      learning signal but does not rely exclusively on motor errors.

PMID- 30224806
TI  - Social subjective value in the primate midbrain.

PMID- 30224807
TI  - Social reward monitoring and valuation in the macaque brain.
AB  - Behaviors are influenced by rewards to both oneself and others, but the neurons
      and neural connections that monitor and evaluate rewards in social contexts are
      unknown. To address this issue, we devised a social Pavlovian conditioning
      procedure for pairs of monkeys. Despite being constant in amount and probability,
      the subjective value of forthcoming self-rewards, as indexed by licking and
      choice behaviors, decreased as partner-reward probability increased. This value
      modulation was absent when the conspecific partner was replaced by a physical
      object. Medial prefrontal cortex neurons selectively monitored self-reward and
      partner-reward information, whereas midbrain dopaminergic neurons integrated this
      information into a subjective value. Recordings of local field potentials
      revealed that responses to reward-predictive stimuli in medial prefrontal cortex
      started before those in dopaminergic midbrain nuclei and that neural information
      flowed predominantly in a medial prefrontal cortex-to-midbrain direction. These
      findings delineate a dedicated pathway for subjective reward evaluation in social
      environments.

PMID- 30224809
TI  - Inhibitory connectivity defines the realm of excitatory plasticity.
AB  - Recent experiments demonstrate substantial volatility of excitatory connectivity
      in the absence of any learning. This challenges the hypothesis that stable
      synaptic connections are necessary for long-term maintenance of acquired
      information. Here we measure ongoing synaptic volatility and use theoretical
      modeling to study its consequences on cortical dynamics. We show that in the
      balanced cortex, patterns of neural activity are primarily determined by
      inhibitory connectivity, despite the fact that most synapses and neurons are
      excitatory. Similarly, we show that the inhibitory network is more effective in
      storing memory patterns than the excitatory one. As a result, network activity is
      robust to ongoing volatility of excitatory synapses, as long as this volatility
      does not disrupt the balance between excitation and inhibition. We thus
      hypothesize that inhibitory connectivity, rather than excitatory, controls the
      maintenance and loss of information over long periods of time in the volatile
      cortex.

PMID- 30224808
TI  - Enhancers active in dopamine neurons are a primary link between genetic variation
      and neuropsychiatric disease.
AB  - Enhancers function as DNA logic gates and may control specialized functions of
      billions of neurons. Here we show a tailored program of noncoding genome elements
      active in situ in physiologically distinct dopamine neurons of the human brain.
      We found 71,022 transcribed noncoding elements, many of which were consistent
      with active enhancers and with regulatory mechanisms in zebrafish and mouse
      brains. Genetic variants associated with schizophrenia, addiction, and
      Parkinson's disease were enriched in these elements. Expression quantitative
      trait locus analysis revealed that Parkinson's disease-associated variants on
      chromosome 17q21 cis-regulate the expression of an enhancer RNA in dopamine
      neurons. This study shows that enhancers in dopamine neurons link genetic
      variation to neuropsychiatric traits.

PMID- 30224810
TI  - CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic
      vasculature.
AB  - Neuroinflammatory diseases, such as multiple sclerosis, are characterized by
      invasion of the brain by autoreactive T cells. The mechanism for how T cells
      acquire their encephalitogenic phenotype and trigger disease remains, however,
      unclear. The existence of lymphatic vessels in the meninges indicates a relevant
      link between the CNS and peripheral immune system, perhaps affecting
      autoimmunity. Here we demonstrate that meningeal lymphatics fulfill two critical
      criteria: they assist in the drainage of cerebrospinal fluid components and
      enable immune cells to enter draining lymph nodes in a CCR7-dependent manner.
      Unlike other tissues, meningeal lymphatic endothelial cells do not undergo
      expansion during inflammation, and they express a unique transcriptional
      signature. Notably, the ablation of meningeal lymphatics diminishes pathology and
      reduces the inflammatory response of brain-reactive T cells during an animal
      model of multiple sclerosis. Our findings demonstrate that meningeal lymphatics
      govern inflammatory processes and immune surveillance of the CNS and pose a
      valuable target for therapeutic intervention.

PMID- 30224812
TI  - Extra Strain Rates in an unsteady spilling breaking wave.
AB  - We analyze the extra strain rates that characterize a curved, thin mixing layer
      induced at an unsteady spilling breaker. We focus on the flow curvature, which
      induces some extra rates of strain that should be accounted for in algebraic-type
      turbulence closures. The comparison between the analytical formulation proposed
      by Brocchini and co-workers for a single-phase turbulent thin layer of fluid and
      the data, obtained from a Particle Image Velocimetry (PIV) dedicated experimental
      program, reveals that the order of magnitude of the extra rates of strain induced
      by the streamline curvature, is comparable with that of the simple shear. This
      differs from what observed for the geometric curvature terms and from what occurs
      at hydraulic jumps, typically used to model steady breakers.

PMID- 30224811
TI  - Differential regulation of chloride homeostasis and GABAergic transmission in the
      thalamus.
AB  - The thalamus is important for sensory integration with the ventrobasal thalamus
      (VB) as relay controlled by GABAergic projections from the nucleus reticularis
      thalami (NRT). Depending on the [Cl-]i primarily set by cation-chloride
      cotransporters, GABA is inhibitory or excitatory. There is evidence that VB and
      NRT differ in terms of GABA action, with classical hyperpolarization in VB due to
      the expression of the Cl- extruder KCC2 and depolarizing/excitatory GABA action
      in the NRT, where KCC2 expression is low and Cl- accumulation by the Cl- inward
      transporter NKCC1 has been postulated. However, data on NKCC1 expression and
      functional analysis of both transporters are missing. We show that KCC2-mediated
      Cl- extrusion set the [Cl-]i in VB, while NKCC1 did not contribute substantially
      to Cl- accumulation and depolarizing GABA action in the NRT. The finding that
      NKCC1 did not play a major role in NRT neurons is of high relevance for ongoing
      studies on the therapeutic use of NKCC1 inhibitors trying to compensate for a
      disease-induced up-regulation of NKCC1 that has been described for various brain
      regions and disease states like epilepsy and chronic pain. These data suggest
      that NKCC1 inhibitors might have no major effect on healthy NRT neurons due to
      limited NKCC1 function.

PMID- 30224813
TI  - Anisotropic Multi-channel Collagen Gel (MCCG) Guides the Growth Direction of the
      Neurite-like Processes of PC12 Cells.
AB  - Hydrogels made of various materials using a variety of methods have been
      extensively studied for use in tissue engineering, and collagen is one of the
      most common material used for its biocompatibility due to it being a major
      component of the extracellular matrix (ECM). Furthermore, the alignment of
      collagen fibres has been shown to direct the growth of neurites, an important
      criterion for engineering nervous tissues. The Multi-channel Collagen Gel (MCCG)
      has collagen fibres aligned circumferentially around the channel structures of
      the gel, and we predicted that the MCCG could guide the growth direction of
      neurites. In this study, we showed that the growth pathway of the neurite-like
      processes of PC12 cells were guided in MCCG but not in normal collagen gel (COL).
      The gelation of collagen gels are known to be affected by ionic concentrations,
      and hence we also investigated the effects of different concentrations of NaCl on
      the properties of MCCG. We found that, despite differences in channel density,
      spacing between channels, and degree of collagen fibre alignment, all MCCGs had
      similar guiding properties on the growth of neurites. Therefore, we believe that
      anisotropic MCCG could be a useful biomaterial for neural tissue engineering in
      the future.

PMID- 30224815
TI  - High ecological complexity in benthic Ediacaran communities.
AB  - A long-running debate over the affinities of the Neoproterozoic 'Ediacara biota'
      has led to contrasting interpretations of Ediacaran ecosystem complexity. A
      'simple' model assumes that most, if not all, Ediacaran organisms shared similar
      basic ecologies. A contrasting 'complex' model suggests that the Ediacara biota
      more likely represent organisms from a variety of different positions on the
      eukaryotic tree and thus occupied a wide range of different ecologies. We perform
      a quantitative test of Ediacaran ecosystem complexity using rank abundance
      distributions (RADs). We show that the Ediacara biota formed complex-type
      communities throughout much of their stratigraphic range and thus likely
      comprised species that competed for different resources and/or created niche for
      others ('ecosystem engineers'). One possible explanation for this pattern rests
      in the recent inference of multiple metazoan-style feeding modes among the
      Ediacara biota; in this scenario, different Ediacaran groups/clades were engaged
      in different methods of nutrient collection and thus competed for different
      resources. This result illustrates that the Ediacara biota may not have been as
      bizarre as it is sometimes suggested, and provides an ecological link with the
      animal-dominated benthic ecosystems of the Palaeozoic era.

PMID- 30224814
TI  - Towards global data products of Essential Biodiversity Variables on species
      traits.
AB  - Essential Biodiversity Variables (EBVs) allow observation and reporting of global
      biodiversity change, but a detailed framework for the empirical derivation of
      specific EBVs has yet to be developed. Here, we re-examine and refine the
      previous candidate set of species traits EBVs and show how traits related to
      phenology, morphology, reproduction, physiology and movement can contribute to
      EBV operationalization. The selected EBVs express intra-specific trait variation
      and allow monitoring of how organisms respond to global change. We evaluate the
      societal relevance of species traits EBVs for policy targets and demonstrate how
      open, interoperable and machine-readable trait data enable the building of EBV
      data products. We outline collection methods, meta(data) standardization,
      reproducible workflows, semantic tools and licence requirements for producing
      species traits EBVs. An operationalization is critical for assessing progress
      towards biodiversity conservation and sustainable development goals and has wide
      implications for data-intensive science in ecology, biogeography, conservation
      and Earth observation.

PMID- 30224816
TI  - A bacterial epidemic in wild plants.

PMID- 30224817
TI  - Seasonal abundance and survival of North America's migratory avifauna determined
      by weather radar.
AB  - Avian migration is one of Earth's largest processes of biomass transport,
      involving billions of birds. We estimated continental biomass flows of nocturnal
      avian migrants across the contiguous United States using a network of 143 weather
      radars. We show that, relative to biomass leaving in autumn, proportionally more
      biomass returned in spring across the southern United States than across the
      northern United States. Neotropical migrants apparently achieved higher survival
      during the combined migration and non-breeding period, despite an average three-
      to fourfold longer migration distance, compared with a more northern assemblage
      of mostly temperate-wintering migrants. Additional mortality expected with longer
      migration distances was probably offset by high survival in the (sub)tropics.
      Nearctic-Neotropical migrants relying on a 'higher survivorship' life-history
      strategy may be particularly sensitive to variations in survival on the
      overwintering grounds, highlighting the need to identify and conserve important
      non-breeding habitats.

PMID- 30224818
TI  - It takes a village.

PMID- 30224819
TI  - NK cell receptor NKG2D sets activation threshold for the NCR1 receptor early in
      NK cell development.
AB  - The activation of natural killer (NK) cells depends on a change in the balance of
      signals from inhibitory and activating receptors. The activation threshold values
      of NK cells are thought to be set by engagement of inhibitory receptors during
      development. Here, we found that the activating receptor NKG2D specifically set
      the activation threshold for the activating receptor NCR1 through a process that
      required the adaptor DAP12. As a result, NKGD2-deficient (Klrk1-/-) mice
      controlled tumors and cytomegalovirus infection better than wild-type controls
      through the NCR1-induced production of the cytokine IFN-gamma. Expression of
      NKG2D before the immature NK cell stage increased expression of the adaptor
      CD3zeta. Reduced expression of CD3zeta in Klrk1-/- mice was associated with
      enhanced signal transduction through NCR1, and CD3zeta deficiency resulted in
      hyper-responsiveness to stimulation via NCR1. Thus, an activating receptor
      developmentally set the activity of another activating receptor on NK cells and
      determined NK cell reactivity to cellular threats.

PMID- 30224820
TI  - MicroRNA says no to mass production.

PMID- 30224821
TI  - The effect of cellular context on miR-155-mediated gene regulation in four major
      immune cell types.
AB  - Numerous microRNAs and their target mRNAs are coexpressed across diverse cell
      types. However, it is unknown whether they are regulated in a manner independent
      of or dependent on cellular context. Here, we explored transcriptome-wide
      targeting and gene regulation by miR-155, whose activation-induced expression
      plays important roles in innate and adaptive immunity. Through mapping of miR-155
      targets through differential iCLIP, mRNA quantification with RNA-seq, and 3'
      untranslated region (UTR)-usage analysis with poly(A)-seq in macrophages,
      dendritic cells, and T and B lymphocytes either sufficient or deficient in
      activated miR-155, we identified numerous targets differentially bound by miR
      155. Whereas alternative cleavage and polyadenylation (ApA) contributed to
      differential miR-155 binding to some transcripts, in most cases, identical 3'-UTR
      isoforms were differentially regulated across cell types, thus suggesting ApA
      independent and cellular-context-dependent miR-155-mediated gene regulation. Our
      study provides comprehensive maps of miR-155 regulatory networks and offers a
      valuable resource for dissecting context-dependent and context-independent miRNA
      mediated gene regulation in key immune cell types.

PMID- 30224822
TI  - NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation
      induced cell death.
AB  - Activation-induced cell death (AICD) of T lymphocytes can be exploited by cancers
      to escape immunological destruction. We demonstrated that tumor-specific
      cytotoxic T lymphocytes (CTLs) and type 1 helper T (TH1) cells, rather than type
      2 helper T cells and regulatory T cells, were sensitive to AICD in breast and
      lung cancer microenvironments. NKILA, an NF-kappaB-interacting long noncoding RNA
      (lncRNA), regulates T cell sensitivity to AICD by inhibiting NF-kappaB activity.
      Mechanistically, calcium influx in stimulated T cells via T cell-receptor
      signaling activates calmodulin, thereby removing deacetylase from the NKILA
      promoter and enhancing STAT1-mediated transcription. Administering CTLs with
      NKILA knockdown effectively inhibited growth of breast cancer patient-derived
      xenografts in mice by increasing CTL infiltration. Clinically, NKILA
      overexpression in tumor-specific CTLs and TH1 cells correlated with their
      apoptosis and shorter patient survival. Our findings underscore the importance of
      lncRNAs in determining tumor-mediated T cell AICD and suggest that engineering
      lncRNAs in adoptively transferred T cells might provide a novel antitumor
      immunotherapy.

PMID- 30224823
TI  - Effects of aging on timing of hibernation and reproduction.
AB  - Small hibernators are long-lived for their size because seasonal dormancy greatly
      reduces predation risk. Thus, within a year, hibernators switch between states of
      contrasting mortality risk (active season versus hibernation), making them
      interesting species for testing the predictions of life-history theory.
      Accordingly, we hypothesized that, with advancing age and hence diminishing
      reproductive potential, hibernators should increasingly accept the higher
      predation risk associated with activity to increase the likelihood of current
      reproductive success. For edible dormice (Glis glis) we show that age strongly
      affects hibernation/activity patterns, and that this occurs via two pathways: (i)
      with increasing age, dormice are more likely to reproduce, which delays the onset
      of hibernation, and (ii) age directly advances emergence from hibernation in
      spring. We conclude that hibernation has to be viewed not merely as an energy
      saving strategy under harsh climatic conditions, but as an age-affected life
      history trait that is flexibly used to maximize fitness.

PMID- 30224824
TI  - Detection and characterisation of multiple herpesviruses in free-living Western
      European hedgehogs (Erinaceus europaeus).
AB  - Sporadic cases of herpesvirus-associated disease have been reported in the
      Western European hedgehog (Erinaceus europaeus), but there has been little
      surveillance for, nor any sequence characterisation of, herpesviruses in this
      species to date. A nested pan-herpesvirus polymerase chain reaction (PCR)
      targeting a region of the DNA polymerase gene was used to test 129 Western
      European hedgehogs from across Great Britain, 2011-2016; 59 (46%) of which were
      PCR-positive. In addition, samples from two previously published cases of fatal
      herpesvirus infection in E. europaeus, from Sweden and Switzerland, were positive
      using this PCR. No statistically significant relationship was detected between
      PCR result and sex, age class, year or season for the British hedgehogs tested.
      In most PCR-positive animals (19/22) from which liver and brain were tested
      separately, both were PCR-positive. Sanger sequencing of amplicons from 59
      British hedgehogs revealed at least two novel viruses within the
      Gammaherpesvirinae. Thirteen of these hedgehogs had liver and brain tissues
      screened for microscopic abnormalities, of which one had non-suppurative
      meningoencephalitis, but neither intranuclear inclusion bodies nor herpesvirus
      virions (on electron microscopical examination) were identified. Sequencing of
      the whole DNA polymerase gene confirmed two genetically different Human
      alphaherpesvirus 1 viruses in the Swedish and Swiss hedgehogs.

PMID- 30224825
TI  - Effects of Unusual Gate Current on the Electrical Properties of Oxide Thin-Film
      Transistors.
AB  - The wide research and development on oxide thin-film transistors (TFTs) have led
      to considerable changes in mainstream technology in various electronic
      applications. Up to now, much research has been focusing on enhancing the
      performance of oxide TFTs and simplifying fabricating process. At the stage of
      research and development in the oxide TFT, unexpectedly high gate current
      phenomena have been continuously reported by several groups, but the origins have
      not been yet studied in detail. The unusual gate current interferes with the
      conductance of the oxide TFT, which makes it difficult to interpret the
      performance of the TFT. Here we present the origin and control factors of the
      unconventional gate currents flow in the oxide TFT. The gate current is due to
      the conduction of electrons through trap sites in insulators, and the current is
      sophisticatedly controlled by the structural factors of TFT. Furthermore, the
      gate current flows only in one direction due to the charge state of the oxide
      semiconductor at the interface with the insulator. We also demonstrate that the
      vertical current path functions as a diode unit can protect the TFT from
      unintended gate electrostatic shock.

PMID- 30224826
TI  - Brcal Defective Breast Cancer Cells Induce in vitro Transformation of Cancer
      Associated Fibroblasts (CAFs) to Metastasis Associated Fibroblasts (MAF).
AB  - It is known that Cancer Associated Fibroblast (CAFs) from the primary tumor site
      can accompany cancer cells to a secondary site during the process of metastasis.
      We hypothesize that these CAFs could be transformed to an altered cell type,
      which can be called as Metastasis Associated Fibroblasts (MAF) in turn can
      support, and convoy cancer cells for metastasis. There are no published reports
      that have characterized and distinguished CAFs from MAF. It is well established
      that some of the cancer cells within the tumor mass accumulate novel mutations
      prior to metastasis. Hence, we speculated that mutations in the tumor suppressor
      gene, BRCA1, which is already reported to induce metastasis via abnormal
      expression of Ezrin, Radixin and Moesin (ERM), could generate MAF. In the present
      study, we demonstrate for the first time that CAFs isolated from primary breast
      cancer tissues when co-cultured with BRCA1 mutated HCC1937 cells transform CAFs
      to MAF in vitro. As expected, MAF augmented proliferation, migration and invasion
      along with over-expression of epithelial mesenchymal transition (EMT) markers,
      Ezrin and CCL5, thereby facilitating metastasis. Therefore, we inhibited Ezrin
      and CCL5 in vitro in MAF and observed that the migration and invasion abilities
      of these cells were attenuated. This highlights the intriguing possibilities of
      combination therapy using MAF inhibitors as anti-metastatic agents along with
      anticancer drugs, to control the metastatic spread from primary tumor site.

PMID- 30224827
TI  - Robust ferromagnetism in hydrogenated graphene mediated by spin-polarized
      pseudospin.
AB  - The origin of the ferromagnetism in metal-free graphitic materials has been a
      decade-old puzzle. The possibility of long-range magnetic order in graphene has
      been recently questioned by the experimental findings that point defects in
      graphene, such as fluorine adatoms and vacancies, lead to defect-induced
      paramagnetism but no magnetic ordering down to 2 K. It remains controversial
      whether collective magnetic order in graphene can emerge from point defects at
      finite temperatures. This work provides a new framework for understanding the
      ferromagnetism in hydrogenated graphene, highlighting the key contribution of the
      spin-polarized pseudospin as a "mediator" of long-range magnetic interactions in
      graphene. Using first-principles calculations of hydrogenated graphene, we found
      that the unique 'zero-energy' position of H-induced quasilocalized states enables
      notable spin polarization of the graphene's sublattice pseudospin. The pseudospin
      mediated magnetic interactions between the H-induced magnetic moments stabilize
      the two-dimensional ferromagnetic ordering with Curie temperatures of Tc = nH *
      34,000 K for the atom percentage nH of H adatoms. These findings show that atomic
      scale control of hydrogen adsorption on graphene can give rise to a robust
      magnetic order.

PMID- 30224828
TI  - Personality Profiles Are Associated with Functional Brain Networks Related to
      Cognition and Emotion.
AB  - Personality factors as defined by the "five-factor model" are some of the most
      investigated characteristics that underlie various types of complex behavior.
      These are, however, often investigated as isolated traits that are conceptually
      independent, yet empirically are typically strongly related to each other. We
      apply Independent Component Analysis to these personality factors as measured by
      the NEO-FFI in 471 healthy subjects from the Human Connectome Project to
      investigate independent personality profiles that incorporate all five original
      factors. Subsequently we examine how these profiles are related to patterns of
      resting-state brain activity in specific networks-of-interest related to
      cognition and emotion. We find that a personality profile of contrasting openness
      and agreeableness is associated with engagement of a subcortical-medial
      prefrontal network and the dorsolateral prefrontal cortex. Likewise, a profile of
      contrasting extraversion and conscientiousness is associated with activity in the
      precuneus. This study shows a novel approach to investigating personality and how
      it is related to patterns of activity in the resting brain.

PMID- 30224830
TI  - Telemedicine for HF management.

PMID- 30224829
TI  - The E3 ubiquitin ligase Trim13 regulates Nur77 stability via casein kinase
      2alpha.
AB  - Nur77 is a member of the NR4A subfamily of nuclear receptors and has been shown
      to regulate various biological processes such as apoptosis and inflammation.
      Here, we show that Nur77 ubiquitination is mediated by the tripartite motif 13
      (Trim13), a RING-type E3 ubiquitin ligase. The interaction between Nur77 and
      Trim13 was confirmed by co-immunoprecipitation. Moreover, we found that Lys539 in
      Nur77 ubiquitination is targeted for Trim13, which leads to Nur77 degradation.
      The Trim13-mediated ubiquitination of Nur77 was optimal in the presence of the E2
      enzyme UbcH5. Importantly, in addition to Trim13-mediated ubiquitination, the
      stability of Nur77 was also regulated by casein kinase 2alpha (CK2alpha).
      Pharmacological inhibition of CK2 markedly increased Nur77 levels, whereas
      overexpression of CK2alpha, but not its inactive mutant, dramatically decreased
      Nur77 levels by promoting Nur77 ubiquitination. CK2alpha phosphorylated Ser154 in
      Nur77 and thereby regulated Nur77 protein levels by promoting its ubiquitin
      mediated degradation. Importantly, we also show that degradation of Nur77 is
      involved in TNFalpha-mediated IL-6 production via CK2alpha and Trim13. Taken
      together, these results suggest that the sequential phosphorylation and
      ubiquitination of Nur77 controls its degradation, and provide a therapeutic
      approach for regulating Nur77 activity through the CK2alpha-Trim13 axis as a
      mechanism to control the inflammatory response.

PMID- 30224831
TI  - Inflammation, protection, and the problems of translation.

PMID- 30224832
TI  - An Exploration of the Spatiotemporal and Demographic Patterns of Ebola Virus
      Disease Epidemic in West Africa Using Open Access Data Sources.
AB  - The purpose of this study was to investigate the utility of exploratory
      analytical techniques using publically available data in informing interventions
      in case of infectious diseases outbreaks. More exactly spatiotemporal and
      multivariate methods were used to characterize the dynamics of the Ebola Virus
      Disease (EVD) epidemic in West Africa, and propose plausible relationships with
      demographic/social risk factors. The analysis showed that there was significant
      spatial, temporal, and spatiotemporal dependence in the evolution of the disease.
      For the first part of the epidemic, the cases were highly clustered in a few
      administrative units, in the proximity of the point of origin of the outbreak,
      possibly offering the opportunity to stop the spread of the disease. Later in the
      epidemic, high clusters were observed, but only in Liberia and Sierra Leone.
      Although not definitely factors of risk, in the setting in which the epidemic
      arose, our analysis suggests infrastructure, access to and use of health
      services, and connectivity possibly accelerated and magnified the spread of EVD.
      Also, the spatial, temporal, and spatiotemporal patterns of epidemic can be
      clearly shown - with evident application in the early stages of management of
      epidemics. In particular, we found that the spatial-temporal analytic tool
      SaTScan may be used effectively during the evolution of an epidemic to identify
      areas for targeted intervention. In the case of EVD epidemic in West Africa,
      better data and integration local knowledge and customs may have been more useful
      to recognize the proper response.

PMID- 30224833
TI  - Water productivity of rainfed maize and wheat: A local to global perspective.
AB  - Water productivity (WP) is a robust benchmark for crop production in relation to
      available water supply across spatial scales. Quantifying water-limited potential
      (WPw) and actual on-farm (WPa) WP to estimate WP gaps is an essential first step
      to identify the most sensitive factors influencing production capacity with
      limited water supply. This study combines local weather, soil, and agronomic
      data, and crop modeling in a spatial framework to determine WPw and WPa at local
      and regional levels for rainfed cropping systems in 17 (maize) and 18 (wheat)
      major grain-producing countries representing a wide range of cropping systems,
      from intensive, high-yield maize in north America and wheat in west Europe to low
      input, low-yield maize systems in sub-Saharan Africa and south Asia. WP was
      calculated as the quotient of either water-limited yield potential or actual
      yield, and simulated crop evapotranspiration. Estimated WPw upper limits compared
      well with maximum WP reported for field-grown crops. However, there was large WPw
      variation across regions with different climate and soil (CV = 29% for maize and
      27% for wheat), which cautions against the use of generic WPw benchmarks and
      highlights the need for region-specific WPw. Differences in simulated evaporative
      demand, crop evapotranspiration after flowering, soil evaporation, and intensity
      of water stress around flowering collectively explained two thirds of the
      variation in WPw. Average WP gaps were 13 (maize) and 10 (wheat) kg ha-1 mm-1,
      equivalent to about half of their respective WPw. We found that non-water related
      factors (i.e., management deficiencies, biotic and abiotic stresses, and their
      interactions) constrained yield more than water supply in ca. half of the
      regions. These findings highlight the opportunity to produce more food with same
      amount of water, provided limiting factors other than water supply can be
      identified and alleviated with improved management practices. Our study provides
      a consistent protocol for estimating WP at local to regional scale, which can be
      used to understand WP gaps and their mitigation.

PMID- 30224834
TI  - Scientific Misconduct: A Global Concern.
AB  - In today's world, evil appears to be all pervading. Medical publication is no
      exception. Scientific misconduct in medical writing is slowly becoming a global
      concern, especially over the last few decades. While the occurrence of such
      events is certainly rare, every researcher and reader should be aware of this
      entity. The researcher should ensure that no inadvertent error is construed as
      misconduct, and should take every effort to guard against it, and the reader
      should have a critical eye for the same. This article looks into various aspects
      of scientific misconduct and encourages awareness regarding the same.

PMID- 30224835
TI  - Effect of Orlistat Versus Metformin in Various Aspects of Polycystic Ovarian
      Syndrome: A Systematic Review of Randomized Control Trials.
AB  - Background: Polycystic ovarian syndrome (PCOS), a commonly prevalent
      endocrinopathy among reproductive age group women, is most often associated with
      obesity. Increased insulin resistance appears to be the central pathophysiologic
      mechanism responsible for various complications of PCOS. This makes 'weight loss'
      as the first-line treatment approach in PCOS. So various trials have tried to
      compare metformin (an insulin-sensitizing agent) and orlistat (an anti-obesity
      drug) aiming to achieve weight loss and hence higher ovulation rate for the group
      of obese PCOS patients. Keeping an eye on all these background facts, we designed
      this systematic review and metaanalysis to compare the effects of metformin and
      orlistat on various aspects of PCOS and to pick the better among the two drugs.
      Materials and Methods: This is a systemic review of randomized control trials
      that studied the effectiveness of orlistat versus metformin in terms of
      improvement in ovulation rate, weight loss, lipid profile, etc. Systematic
      literature search over the period January 2000-December 2016 was performed in the
      following electronic databases: Medline, embase, google scholar, pubmed and The
      Cochrane Library and only randomized controlled clinical trials were included in
      our study. All authors carefully went through all sources of information
      independently. Results: According to this study, weight loss, testosterone level
      after 4 weeks of treatment, total serum cholesterol and triglyceride level showed
      significant fall in orlistat-treated group. Conclusion: Our review shows that
      orlistat is a more effective drug than metformin and should be the preferred drug
      in obese PCOS in combination with weight loss.

PMID- 30224836
TI  - Difficult Deliveries in Cesarean Section.
AB  - Cesarean section rate has been on the rise. It is commonly perceived as a simple
      and safe alternative to difficult vaginal birth. However, there are situations
      during C section where delivery of fetus may be difficult. This can cause
      maternal and fetal complications. To avoid such mishaps, anticipation of
      potential difficulties and planning in advance can be fruitful. This amounts to
      mobilization of a good team of anesthetist, assistant and skilled neonatologist.
      Proper technical skills are needed not only to use the equipment but to deal with
      such situations for safe delivery of the fetus. The training in technical skills
      can be imparted through drill protocols under C section skills. This way, one
      should try and accomplish safe atraumatic fetal delivery.

PMID- 30224837
TI  - Role of Ultrasonographic Placental Thickness in Prediction of Fetal Outcome: A
      Prospective Indian Study.
AB  - Background Information: Placenta is the connecting organ between the mother and
      the fetus. It supplies oxygen and all the necessary elements for the growth and
      development of the fetus. In normal pregnancy, the growth of the placenta remains
      concordant with the growth of the fetus. The sonographic assessment of placenta
      can give information about the nutritional status of the fetus. It is known that
      normal placental thickness approximately equals gestational age. It is
      historically documented that placental weight is one-fifth of the fetal weight
      and abnormally thin or thick placenta is associated with increased incidence of
      perinatal morbidity and mortality. However, there are very few studies
      correlating placental thickness with Neonatal outcome. Objectives: To correlate
      ultrasonographic placental thickness at 32 and 36 weeks pregnancy with neonatal
      outcome. To propose placental thickness as a simple test for prediction of
      neonatal outcome. Methods: Placental thickness at 32 and 36 weeks was measured by
      ultrasound, in 130 pregnant mothers with confirmed dates and uncomplicated
      singleton pregnancy. Placental thickness was categorized as normal (10th-95th
      percentile), thin (<10th percentile) and thick (>95th percentile) at each stage
      and was correlated with birth weight and neonatal outcome. Results: Neonatal
      outcome was good in women with normal placental thickness (10th-95th percentile)
      at 32 and 36 weeks and was compromised in women with thin (<10th percentile) and
      thick (>95th percentile) placentae. Conclusion: Placental thickness at 32 and 36
      weeks corresponds well with gestational age and is a good prognostic factor in
      assessing neonatal outcome. Therefore, placental thickness should be measured in
      addition to biometric parameters in antenatal women undergoing ultrasound.

PMID- 30224838
TI  - Efficacy of Antiviral Therapy in HBsAg-Positive Pregnant Women to Reduce Mother
      to-Infant Transmission of Hepatitis B Virus.
AB  - Background and Objectives: Hepatitis B is a major health concern in Asia. Chronic
      hepatitis B virus (HBV) infection may cause hepatic cirrhosis and liver cancer.
      HBV is transmitted horizontally through blood and blood products and vertically
      from mother to infant. Perinatal infection is the main route of transmission in
      regions with high prevalence of hepatitis B surface antigen (HbsAg) carriage, and
      perinatal transmission leads to high rates of chronic infection. Therefore, it is
      important to prevent mother-to-child transmission (MTCT) of HBV1. The present
      study aims at comparing the use of antivirals (lamivudine vs tenofovir) in
      reducing MTCT. Materials and Methods: A total of 60 HbsAg-positive pregnant women
      were enrolled in the prospective study to test the efficacy of antiviral
      (lamivudine vs tenofovir-category B drug) to reduce mother-to-child transmission
      and monitor hepatitis B viral status in infant. HbsAg-positive pregnant women
      aged 18-43 years at gestational age between 28 and 32 weeks were followed up.
      They were tested for HBsAg, liver function test and HBeAg. In whom HbeAg was
      positive, HBV viral load was tested. Sixty patients with high viral load (>6 log
      copies/ml) were recruited in the study. Alternate patients were randomized into
      two groups. Group A comprised 31 subjects treated with lamivudine 100 mg daily
      starting from 28 to 32 weeks of gestation (third trimester) and continued to 1
      month after delivery. Group B comprised 29 pregnant women who were treated with
      tenofovir 300 mg daily from 28 to 32 weeks of gestation and continued to 1 month
      post-partum. The newborn babies were given HBIG within 24 h after delivery and
      HBV vaccines at 0, 1 and 6 months. HBsAg infectivity was tested in the infant at
      1 year after birth. Results: Antivirals, lamivudine/tenofovir treatment in HBV
      carrier mothers from 28 weeks of gestation along with active and passive
      immunization of new born may interrupt MTCT of HBV efficiently. Tenofovir,
      category B drug, is more effective in preventing transmission of HBV infection to
      infants (p = 0.004).

PMID- 30224839
TI  - New Evidence to Support Antibiotic Prophylaxis in Meconium-Stained Amniotic Fluid
      in Low-Risk Women in Labor a Prospective Cohort Study.
AB  - Purpose of study: To assess the maternal and perinatal complications associated
      with meconium-stained amniotic fluid (MSAF) in low-risk women in labor. Methods:
      This prospective cohort study was conducted at CMC Hospital, Vellore, India. Two
      hundred low-risk women who had artificial or spontaneous rupture of membranes
      after admission with MSAF were included in the study. Two hundred similar women
      with clear liquor were taken as controls. The primary outcomes considered were
      the incidence of chorioamnionitis and endomyometritis in the mothers. The
      secondary outcomes included postpartum hemorrhage and retained placenta in the
      mothers and respiratory distress, meconium aspiration, sepsis, and NICU admission
      in the newborn. Statistical analysis was done using Fischer exact test. Odds
      ratio, 95% confidence interval, and P value were estimated. Results: Compared to
      controls, those with MSAF had significantly higher rates of chorioamnionitis (2
      vs. 8%, P = 0.006) and endomyometritis (3 vs. 9.5% P = 0.007). Among the
      secondary end points, only neonatal respiratory distress (8.5 vs. 1.5%; P =
      0.001) and meconium aspiration (4 vs. 0%; P = 0.007) were found to be
      significantly increased in the meconium group. Conclusion: Statistically
      significant increased incidence of chorioamnionitis and endomyometritis in women
      with MSAF in labor established in our study strongly supports the use of
      prophylactic antibiotics in these women to prevent immediate and long-term
      consequences.

PMID- 30224840
TI  - Prenatal Diagnosis of Choroid Plexus Cyst: What Next?
AB  - Introduction and Objective: Fetal choroid plexus cysts (CPC) are often detected
      on prenatal ultrasounds and pose a need to formulate protocol for management and
      counseling. Methodology: A total of 1024 unselected cases between gestational
      ages 11 and 20 weeks were sonologically screened for CPC in 1-year period. On
      ultrasound, CPC are seen as sonolucent spaces in the echogenic choroid plexus of
      lateral ventricles of brain measuring at least 2-3 mm in diameter. Those
      diagnosed with CPC were subjected to thorough anomaly scan. Prenatal karyotype
      was offered in cases of associated anomalies. Results: The incidence of CPC is 1%
      (10/1024) in this study. Associated anomalies were found in 20% (2/10) of cases,
      which were offered invasive testing for fetal karyotype. All the cases with
      isolated CPC had good outcome. Conclusions: Isolated CPC with low-risk
      biochemical screening for aneuploidies are now considered normal variants rather
      than a pathology, need no invasive testing and carry a good prognosis. CPC
      associated with other anomalies warrant invasive testing and are more likely to
      be associated with Trisomy 18.

PMID- 30224841
TI  - Umbilical Coiling Index Assessment During Routine Fetal Anatomic Survey: A
      Screening Tool for Fetuses at Risk.
AB  - Background: The umbilical cord is the lifeline of the foetus as it supplies
      water, nutrients, and oxygen. Protection of these blood vessels is needed and
      provided by Wharton's Jelly, amniotic fluid and the helical pattern, or coiling,
      of the umbilical cord vessels. Aim: To establish the relationship between
      antenatal umbilical cord coiling index (aUCI) measured at 18-20 weeks along with
      level II USG and adverse perinatal outcomes. Methods: A cross-sectional study was
      conducted on 408 antenatal women, enrolled at the time of fetal anatomic survey,
      and their cord coiling index (aUCI) was measured, and its association with
      perinatal outcomes was observed. Umbilical coiling index was classified as
      Hypocoiled if UCI <10th percentile, hypercoiled >90th percentile, normocoiled
      between 10th and 90th percentile. Results: 408 antenatal women were enrolled for
      the study. Mean aUCI was 0.43 +/- 0.30 (normocoiled group), 0.18 +/- 0.4
      (hypocoiled), and 0.53 +/- 0.05 (hypercoiled group). The average gestational age
      at delivery in hypocoiled group was 36.8 +/- 2.34 weeks, and it was shorter than
      38.3 +/- 1.82 weeks of the normocoiled group and 38.9 +/- 1.72 weeks of the
      hypercoiled group. Mean birth weight observed was 2055 +/- 744 (hypocoiled
      group), 3049 +/- 564 (hypercoiled), and 3102 +/- 564 (normocoiled) p < 0.001.
      Preterm births 52 (59%) and low birth weight 76 (69%) were significantly
      associated with hypocoiling. Conclusion: Abnormal umbilical cord coiling index,
      detected at the fetal ultrasound anatomic survey in the second trimester (18-20
      weeks), can be used potentially as a screening or as a predictive tool for
      adverse antenatal or perinatal events.

PMID- 30224842
TI  - Comparison of Efficacy and Safety of Intravenous Labetalol Versus Hydralazine for
      Management of Severe Hypertension in Pregnancy.
AB  - Background: There is no consensus about the better intravenous drug between
      Hydralazine and Labetalol to control hypertension in cases of severe hypertension
      in pregnancy. Both drugs have their own advantages and disadvantages. Methods:
      This is a prospective randomized controlled trial comparing the efficacy and
      safety of intravenous Labetalol versus Hydralazine for management of severe
      hypertension in pregnancy. A total of 152 eligible subjects were randomised in
      two groups consisting 76 subjects each by envelope method. Both the groups were
      comparable with respect to systolic, diastolic and mean arterial blood pressure
      at admission. One group received Labetalol and the other Hydralazine. The number
      of drug doses, the time taken to achieve target blood pressure and side-effects
      were noted. Results: With a single dose, Labetalol (81.5%) was able to achieve
      target blood pressure in a significantly higher number of cases as compared to
      Hydralazine (69.5%). Labetalol could help in achieving the target blood pressure
      faster than Hydralazine. The incidence of maternal adverse effects was comparable
      between the groups. Fetal outcome was comparable in both groups. Conclusion:
      Hydralazine and Labetalol both were found to be equally efficacious in reducing
      blood pressure in cases of severe hypertension in pregnancy. Labetalol achieved
      the target blood pressure faster than Hydralazine. The adverse effects of both
      the drugs were comparable.

PMID- 30224843
TI  - Role of Aspirin in High Pulsatility Index of Uterine Artery: A Consort Study.
AB  - Background: Preeclampsia is a heterogeneous disorder prevalent in 3-10% of
      pregnant women globally. The etiology is multifactorial. There is a initial stage
      of endothelial dysfunction and placental ischemia (Stage 1); this leads to
      maternal syndrome of hypertension, edema, and proteinuria (Stage 2). Drugs acting
      on immunomodulatory, anti-inflammatory, antioxidant and proresolving pathways can
      minimize the complications of preeclampsia. The therapeutic effect of aspirin is
      based on acetyl group and salicylate group. Both components have independent
      therapeutic effects on anti-inflammatory pathway and proresolving pathway. Aims
      and Objectives: This study was designed to assess the effectiveness and safety of
      aspirin in prevention and treatment of symptoms and complications of preeclampsia
      in women at high risk of preeclampsia. Methods: This is a prospective
      experimental study to evaluate the effectiveness of aspirin versus placebo in the
      prevention of maternal syndrome of preeclampsia in women with high risk of
      preeclampsia (G1 = 97, G2 = 92). Patients with age >= 34, chronic hypertension,
      multiple pregnancies, gestational diabetes, and high pulsatility index of uterine
      artery were enrolled between 12 and 20 weeks of gestation and prescribed 75 mg
      aspirin daily till 34 weeks of gestation. Control group was not prescribed
      aspirin. Observations and Results: There was a reduction in relative risk of
      preeclampsia in aspirin group as compared with control group. There was no
      significant increase in the number of cases of abruption placenta, preterm
      delivery, neonatal intraventricular hemorrhage, patent ductus arteriosus, and
      postpartum hemorrhage following aspirin therapy. Conclusion: In patients with
      high mean pulsatility index of uterine arteries, low dose aspirin can be a useful
      intervention. Uterine artery Doppler is a simple and noninvasive test which can
      be used safely for the prediction of preeclampsia. Aspirin is safe, economical,
      and easily available commercially.

PMID- 30224844
TI  - Vitamin D Status in Mothers and Their Newborns and Its Association with Pregnancy
      Outcomes: Experience from a Tertiary Care Center in Northern India.
AB  - Objective: Study was planned to know vitamin D status in mothers and their
      newborns and effect of vitamin D deficiency on pregnancy outcome. Study design:
      Two hundred consecutive pregnant women with singleton pregnancy admitted to the
      labor ward of a tertiary care center were recruited for the study. Maternal and
      cord blood samples were taken and analyzed for 25(OH) D level. Maternal and fetal
      outcomes were studied. Results: High prevalence of hypovitaminosis D was found
      among pregnant women. Eighty-six percentage had vitamin D deficiency, 9.5% had
      insufficiency, and only 4.5% had sufficient vitamin D level. Women with
      preeclampsia had statistically significant vitamin D deficiency and insufficiency
      as compared to patients who had normal blood pressure levels (p = 0.04). Cesarean
      section rate was significantly higher in patients with vitamin D deficiency and
      insufficiency compared to sufficient group (p = 0.004). Cord blood 25(OH) D
      levels strongly correlated with maternal serum 25 (OH) D levels (p = 0.001,
      correlation coefficient r = 0.84). Conclusions: This study showed a very high
      prevalence of hypovitaminosis D among pregnant women and excellent correlation
      between maternal and fetal 25(OH) D levels. Hypovitaminosis D was associated with
      preeclampsia, increased Cesarean rate, and low birth weight babies.

PMID- 30224845
TI  - Outcome of Pregnancy with Hemoglobinopathy in a Tertiary Care Center.
AB  - Purpose: The objective was to observe the characteristics among pregnant patients
      with a diagnosed hemoglobinopathy and to study the obstetric and medical
      morbidity patterns during the antenatal and the perinatal periods in this group
      of patients. Methods: A prospective observational study was conducted in a
      tertiary care center. Results: Sixty patients were studied in 11 months.
      Primigravidae (43.3%) formed the highest percentage of patients. beta Thalassemia
      trait was the most common hemoglobinopathy, seen in 81.66% of study subjects. The
      hemoglobin value ranged from 5.7 to 13.0, with an average of 9.2 g/dl. Thyroid
      problems were the most common associated medical disorder. Though IUGR and
      placenta previa were common, there were no major obstetric problems. There were
      57 live births and 1 fresh stillbirth. Two patients had spontaneous abortion for
      which uterine curettage was done. LSCS was the most common obstetric outcome.
      Patients with sickle-cell disease required more blood transfusion than those with
      beta-thalassemia trait. There were 2 maternal mortalities, and both the patients
      were the diagnosed cases of sickle-cell disease. Conclusions: While the perinatal
      outcomes among women with sickle-cell disease are poor, the outcomes in pregnant
      patients with beta-thalassemia trait were not a cause of major concern.

PMID- 30224846
TI  - How Adequate are Macro- and Micronutrient Intake in Pregnant Women with Diabetes
      Mellitus? A Study from South India.
AB  - Background: Diabetes is the most common condition in pregnancy with a worldwide
      prevalence of 16.9%. Aim: To determine the adequacy of the nutrient intake of
      pregnant women with diabetes mellitus. Methods: This is a cross-sectional study
      of 85 pregnant women who met the diagnostic inclusion criteria for diabetes
      mellitus (gestational and pre-gestational diabetes mellitus) and who were being
      managed at the outpatient clinic of a tertiary care teaching hospital. Their
      demography, clinical characteristics (from updated medical records),
      anthropometric measures (using standard procedures), nutrient intake and meal
      pattern (obtained using 24 h recall, food frequency and their log diaries) were
      collected. Results: The mean age of the group was 29.9 + 4.5 years, 54% were in
      the second trimester of pregnancy with a mean glycosylated haemoglobin level of
      6.3 + 1.4%. The mean BMI indicated that 47% of them were in the obese grade 1
      category. Insulin was used in one-third of the population. The overall
      macronutrient and micronutrient intakes of the population were below the
      recommended daily allowances for Indians (60-70% of RDA). There was a deficit in
      the intake of calories, fibre, proteins, iron, calcium, carotene, folic acid,
      thiamine, riboflavin and niacin. Between the two groups, the pre-GDM women had a
      significantly better nutrient intake and this could be attributed to a greater
      exposure to nutrition counselling that they have received during the earlier part
      of their diabetes care. Conclusion: The gestational period should be viewed as a
      window of opportunity to modify dietary patterns and introduce healthy lifestyle
      practices for the woman and her family.

PMID- 30224847
TI  - Sequential Versus Concurrent Use of Vaginal Misoprostol Plus Foley Catheter for
      Induction of Labor: A Randomized Clinical Trial.
AB  - Background: To compare between the sequential and concurrent use of vaginal
      misoprostol plus Foley catheter for labor induction. Methods: This single-center,
      non-blinded randomized study was conducted at the department of Obstetrics and
      Gynecology, Faculty of medicine, Zagazig University. A total of 160 women with
      full term singleton pregnancy, cephalic presentation and bishop score <= 6 were
      randomized for labor induction with either concurrent or sequential use of
      vaginal misoprostol plus Foley catheter (80 cases in each group). The primary
      outcome measured was induction-to-delivery interval and secondary outcomes
      mesaured were vaginal delivery within 24 h, number of doses needed to induce
      labor, need of oxytocin for augmentation of labor, cesarean section rate,
      maternal or neonatal complications. Results: The mean induction-to-delivery
      interval was 22.33 +/- 13.28 h versus 18.45 +/- 14.34 h (p = 0.041) in sequential
      and concurrent group, respectively. The percentage of women who completed vaginal
      delivery within 24 h was 51% versus 61% (p = 0.046) in sequential and concurrent
      group, respectively. Other maternal and neonatal outcomes were similar in both
      groups. Conclusion: Concurrent use of vaginal misoprostol plus Foley catheter for
      labor induction was associated with shorter induction-to delivery interval
      compared to sequential use, and it increases the rate of vaginal delivery in the
      first 24 h.

PMID- 30224848
TI  - A Case of Recurrent First Trimester Miscarriages Due to Inherited Multifactorial
      Thrombophilia in an Otherwise Asymptomatic Patient: A Clinical Dilemma.

PMID- 30224849
TI  - Nimotuzumab in the Management of Recurrent Endometrial Carcinoma: A Case Report.

PMID- 30224850
TI  - In-Bag Contained Power Morcellation Technique.

PMID- 30224851
TI  - Intrapartum Hypomagnesemic Tetany: A Manifestation of an Ignored Element.

PMID- 30224852
TI  - Long leg splinting for pediatric femur fractures.
AB  - Background: Pediatric femur fractures are frequently encountered injuries
      frequently treated with spica casting. Spica casting may, however, be expensive
      and burdensome to patients. A possible alternative is a long leg splint. Methods:
      Patients aged 6 months to 5 years old who were treated for a femoral shaft
      fracture with a long leg splint extending above the waist were matched with a
      patient treated with a spica cast. Results: At the time of healing, the alignment
      in the spica cast group was only significantly better than the alignment of the
      splint group with respect to coronal angulation.

PMID- 30224853
TI  - Finite element analysis of the foot: Stress and displacement shielding.
AB  - The foot is at the base of the antigravity control system (postural or
      equilibrium system) that allows the man to assume the upright posture and to move
      in the space. This podalic cohesion is achieved by the capsulo-ligamentous and
      aponeurotic formations to which are added the muscular formations with functions
      of "active ligaments" and postural. A three-dimensional (3D) finite element model
      of human foot was developed using the real foot skeleton and soft tissue
      geometry, obtained from the 3D reconstruction of MR images. The plantar fascia
      and the other main ligaments were simulated using truss elements connected with
      the bony surfaces. Bony parts and ligaments were encapsulated into a skin of soft
      tissues, imposing a linear elastic behavior of material in the first case and the
      hyperelastic law in the second. The model was tested by applying a load of 350 N
      on the top of the talus and the reaction force applied on the Achilles tendon
      equal to 175 N acting, and putting it in contact with a rigid wall. The results
      evidence that the most stressed areas, localized around the calcaneus following a
      trajectory that includes the cuboid and spreading into metatarsals and first
      phalanges. The foot is a "spatial" structure perfectly designed to absorb and
      displace the forces, brought back to the infinite planes of the space.

PMID- 30224854
TI  - Loop and knot security of a novel arthroscopic sliding-locking knot using high
      strength sutures.
AB  - Objective: We evaluated the loop and knot security of a novel arthroscopic knot,
      the Wiese knot, using different types of sutures. Methods: The Wiese knot was
      tied using four different brands of braided sutures (Ethibond, Orthocord,
      FiberWire, and UltraBraid) with and without a series of three reversing half
      hitches (RHAPs) and tested for loop and knot security. Results: Orthocord
      provided the greatest amount of loop security. FiberWire delivered the highest
      knot security. UltraBraid had the greatest ultimate force. Three half-hitches
      increased the maximal load to clinical failure. Conclusion: The biomechanical
      characteristics of the Wiese knot are affected by suture material qualities.

PMID- 30224855
TI  - Association of MTHFR and TNF-alpha genes polymorphisms with susceptibility to
      Legg-Calve-Perthes disease in Iranian children: A case-control study.
AB  - Objective: The aim of this study was to assess the association of MTHFR and TNF
      alpha genes polymorphisms with Legg-Calve-Perthes' disease (LCPD) risk in the
      Iranian children. Methods: A total of 45 children with LCPD and 55 healthy
      controls were recruited to the study. Genotyping was performed via the RFLP-PCR
      method and genetic risk was calculated by odds ratio (OR) with its corresponding
      95% confidence interval (CI). Results & conclusion: Our case-control study failed
      to determine any association of MTHFR (677C > T and 1298A > C) and TNF-alpha (
      308G > A and -238G > A) polymorphisms with LCPD risk. More studies with larger
      sample size are warranted to validate our findings.

PMID- 30224856
TI  - Correlation of intra-operative hamstring autograft size with pre-operative
      anthropometric and MRI measurements.
AB  - The purpose of this study was to compare various pre-operative methods of
      estimating intra-operative hamstring autograft size. A retrospective review was
      completed on 74 patients who had an anterior cruciate ligament reconstruction
      performed using a quadruple-looped hamstring autograft from July 2007-April 2015
      at a single institution. A positive correlation was observed between intra
      operative graft size and pre-operative imaging using two methods of MRI
      measurements. Correlation existed between hamstring size and patient height and
      weight, but not age or BMI. Thus, pre-operative MRI and anthropometric
      measurements can be used to estimate intra-operative hamstring graft size.

PMID- 30224857
TI  - Restoration of center of rotation and balance of THR.
AB  - Improvements in early hip arthroplasties focused on surgical techniques with
      subsequent studies emphasizing restoration of the hip center of rotation for
      longevity of the implant. Current literature suggests femoral stem anteversion of
      10-20 degrees , cup anteversion of 20-25 degrees  and a combined anteversion of
      25-40 degrees  in males, 30-45 degrees  in females. Inclination goal appears to
      be 45 degrees  precisely to balance between impingement & dislocation versus edge
      loading & accelerated wear. Restoration of the acetabular center of rotation will
      improve joint reactive forces and reduce wear. Here we describe techniques to
      achieve a well balanced total hip with restoration of the center of rotation.

PMID- 30224858
TI  - Strongly localized magnetic reconnection by the super-Alfvenic shear flow.
AB  - We demonstrate that the dragging of the magnetic field by the super-Alfvenic
      shear flows out of the reconnection plane can strongly localize the reconnection
      x-line in collisionless pair plasmas, reversing the current direction at the x
      line. Reconnection with this new morphology, which is impossible in resistive
      magnetohydrodynamics, is enabled by the particle inertia. Surprisingly, the quasi
      steady reconnection rate remains of order 0.1 even though the aspect ratio of the
      local x-line geometry is larger than unity, which completely excludes the role of
      tearing physics. We explain this by examining the transport of the reconnected
      magnetic flux and the opening angle ma de by the upstream magnetic field,
      concluding that the reconnection rate is still limited by the constraint imposed
      at the inflow region. Based on these findings, we propose that this often
      observed fast rate value of order 0.1 itself, in general, is an upper bound value
      determined by the upstream constraint, independent of the localization mechanism
      and dissipation therein.

PMID- 30224859
TI  - Prevalence of Sexually Transmitted Infections among Married Women in Rural Nepal.
AB  - Introduction: We have previously determined the prevalence of human
      papillomavirus (HPV) infection among women in rural Nepal. In the current study,
      we also wanted to examine the prevalence of and risk factors for other sexually
      transmitted infections (STIs) in the same population. Methods: Population-based
      study of nonpregnant women >= 15 years who were married or had a history of
      marriage in the past, residing in five rural villages in Nepal. Data on
      sociodemographic characteristics, reproductive history, and genitourinary
      symptoms were collected, and a gynecological examination was conducted. Cervical
      samples were analyzed by real-time PCR for Neisseria gonorrhoeae, Chlamydia
      trachomatis, and Trichomonas vaginalis and HPV, and a serum sample was analyzed
      for syphilis, hepatitis B virus (HBV) and HIV infection by serology. Results: Of
      2416 eligible women, 62% participated. Trichomoniasis, Chlamydia trachomatis
      infection, HPV and HBV infection, and syphilis were detected in 5.4%, 0.8%,
      14.3%, 0.3%, and 0.2% of the women. None had gonorrhea or HIV infection. Of those
      with genitourinary symptoms, 6.3% had a curable STI. Vaginal discharge classified
      as abnormal by gynecological examination, but not self-reported discharge, was
      significantly associated with laboratory diagnosis of a curable STI. Risk factors
      for trichomoniasis were reproductive age and high cast/ethnicity. Due to low
      prevalence, risk factors for other STIs could not be disclosed. Conclusion: We
      observed high prevalence of HPV infection followed by trichomoniasis, while other
      STIs were rare among women in rural Nepal. There was no association between
      genitourinary symptoms and laboratory-confirmed STIs.

PMID- 30224860
TI  - An Introduction to the Mathematical Modeling in the Study of Cancer Systems
      Biology.
AB  - Background: Frequently occurring in cancer are the aberrant alterations of
      regulatory onco-metabolites, various oncogenes/epigenetic stochasticity, and
      suppressor genes, as well as the deficient mismatch repair mechanism, chronic
      inflammation, or those deviations belonging to the other cancer characteristics.
      How these aberrations that evolve overtime determine the global phenotype of
      malignant tumors remains to be completely understood. Dynamic analysis may have
      potential to reveal the mechanism of carcinogenesis and can offer new therapeutic
      intervention. Aims: We introduce simplified mathematical tools to model serial
      quantitative data of cancer biomarkers. We also highlight an introductory
      overview of mathematical tools and models as they apply from the viewpoint of
      known cancer features. Methods: Mathematical modeling of potentially actionable
      genomic products and how they proceed overtime during tumorigenesis are explored.
      This report is intended to be instinctive without being overly technical.
      Results: To date, many mathematical models of the common features of cancer have
      been developed. However, the dynamic of integrated heterogeneous processes and
      their cross talks related to carcinogenesis remains to be resolved. Conclusions:
      In cancer research, outlining mathematical modeling of experimentally obtained
      data snapshots of molecular species may provide insights into a better
      understanding of the multiple biochemical circuits. Recent discoveries have
      provided support for the existence of complex cancer progression in dynamics that
      span from a simple 1-dimensional deterministic system to a stochastic (ie,
      probabilistic) or to an oscillatory and multistable networks. Further research in
      mathematical modeling of cancer progression, based on the evolving molecular
      kinetics (time series), could inform a specific and a predictive behavior about
      the global systems biology of vulnerable tumor cells in their earlier stages of
      oncogenesis. On this footing, new preventive measures and anticancer therapy
      could then be constructed.

PMID- 30224861
TI  - Drug-Induced Interstitial Lung Disease from a Misdiagnosed Infection.

PMID- 30224862
TI  - Autonomic Symptoms and Allodynia in Migraine.

PMID- 30224863
TI  - Electrophysiological Subtypes and Prognostic Factors of Childhood Guillain-Barre
      Syndrome.
AB  - Introduction: We assessed the clinical, epidemiologic, electrophysiological and
      prognostic characteristics of childhood Guillain-Barre Syndrome admitted to 13
      pediatric neurology centers in Turkey. Method: Using a standard data recording
      form age, sex, duration of symptoms, distribution of weakness at onset, cranial
      nerve involvement, cerebrospinal fluid findings, electrophysiological findings,
      duration of hospitalization, requirement of ventilation, treatment and clinical
      evaluation scale at onset, discharge and 1, 3, 6, and 12 months after discharge
      were recorded. Results: Among the 236 children with a median age of 6.8 years
      there was a male to female ratio of 1.3. Based on the electrophysiological
      features; 84 patients were classified as acute inflammatory demyelinating
      polyrediculoneuropathy (AIDP), 61 as acute motor axonal neuropathy (AMAN), 21 as
      acute motor-sensory axonal neuropathy (AMSAN). The incidence of cranial nerve
      involvement was 16%, and was related to lower clinical scores at discharge and 6
      months after discharge. Clinical scale scores between axonal and demyelinating
      subgroups did not show statistically significant difference except for admission
      (p<0.05). Conclusion: Electrophysiological subtypes are not important in
      prognosis in our series. However, duration of weakness, duration of
      hospitalization and ventilation requirement can affect prognosis negatively.

PMID- 30224864
TI  - Comparison of Language Features, Autism Spectrum Symptoms in Children Diagnosed
      with Autism Spectrum Disorder, Developmental Language Delay, and Healthy
      Controls.
AB  - Introduction: Language and communication is very important in social, emotional,
      and cognitive development of children. Delay in language is the first complaint
      for children diagnosed with autism spectrum disorder (ASD) or developmental
      language delay (DLD). In this study it is aimed to evaluate and compare language
      profiles and autistic symptoms between children diagnosed with ASD, DLD, and
      healthy controls. Method: Twenty-six children who are diagnosed with ASD, 43
      children who are diagnosed with DLD, and 47 healthy controls are included to
      study; and all children are in the age of 48-72 months. Test of Early Language
      Development was used to evaluate language profiles, and autism spectrum symptoms
      were evaluated with social communication questionnaire (SCQ). Results: The
      sociodemographic features of groups were similar. The statistical significant
      differences were found in all language subscales and subscales of SCQ among three
      groups. Both children who were diagnosed with ASD and DLD had more autism
      spectrum symptoms when compared to controls. Discussion: In present study, it is
      indicated that developmental language trajectories are different in ASD and DLD
      group. Children, who are diagnosed with ASD, have more receptive language
      difficulties while children, who are diagnosed with DLD, have more language
      difficulties in expressive language area. The finding, children who are diagnosed
      with DLD have more autistic symptoms, shows that autistic symptoms are related
      with language development, and it is very important to give preference to
      language education in the treatment.

PMID- 30224865
TI  - The Relation of Circulating Levels of Leptin with Cognition in Patients with
      Alzheimer's Disease.
AB  - Introduction: To investigate the relation of circulating levels of leptin with
      cognition in Alzheimer's disease (AD) patients. Methods: Thirty patients meeting
      the clinical diagnostic criteria for AD, and twenty-five healthy controls were
      enrolled into the study. At baseline, all patients underwent standing height,
      weight measurements, and waist circumference (in centimeters) using a standard
      scale. Body mass index (BMI) was then calculated as weight (in kilograms). A
      single 5-ml fasting blood sample was obtained from each patient. All subjects
      were evaluated by Turkish version of Mini Mental State Examination (MMSE),
      Clinical Dementia Rating (CDR) and Global Deterioration Scale (GDS). Results: The
      mean age of patients and controls were 72.33+/-10.11 and 67.20+/-8.95,
      respectively. There was not any significant difference between age of the
      patients and the controls (p=0.054). Both patient and control groups consisted of
      mostly women (60% and 56% respectively). The mean waist circumferences (WC) of
      patients and controls were 95.46+/-10.87 and 97.76+/-10.07, respectively and was
      not statistically different (p=0.424). The mean serum leptin levels in patients
      and controls were 5.49+/-4.06 ng/dL 5.71+/-4.45 ng/dL, respectively. Leptin
      levels were not statistically different between patients and controls (p=0.84).
      The mean MMSE scores of AD patients and controls were 17+/-6.54 and 27.32+/-2.15
      respectively, and AD patients had significantly lower MMSE scores than the
      controls (p=0.000). The mean BMI of patients and controls were 25.72+/-3.98 and
      27.92+/-3.08 respectively. The BMI of controls were higher than patients and
      there was statistically significant difference between two groups (p=0.029). In
      the patient group, there were no correlations between leptin levels and age
      (p=0.067), BMI (p=0.098), WC (p=0.113), MMSE (p=0.203), CDR (p=0.519) and GDS
      (p=0.587). Similarly in control group leptin levels were not correlated with BMI
      (p=0.718), WC (p=0.755) and MMSE (p=0.859). Conclusion: In the present study, we
      could not find any relation between blood leptin levels and cognition in AD
      patients.

PMID- 30224866
TI  - Investigation of Copy Number Variation by arrayCGH in Turkish Children and
      Adolescents Diagnosed with Autism Spectrum Disorders.
AB  - Aim: The development of whole-genome screening methodologies for the detection of
      copy number variations (CNVs), such as array-based comparative genomic
      hybridization (aCHG), provides a much higher resolution than karyotyping leading
      to the identification of novel microdeletion and microduplication syndromes often
      associated with an autism spectrum disease (ASD) phenotype. The aim of the study
      was to determine CNVs of patients with ASD by using array-based comparative
      genomic hybridization. Methods: Fifty-three patients diagnosed with ASD between
      20.01.2014 and 14.01.2015 were included in the study. Chromosome analysis of the
      patients was performed from peripheral blood cultures and analysed as normal. All
      patients were evaluated with P064C1 and P096A2 MLPA probes in terms of 16 mental
      retardation related syndromes. For aCGH method, SurePrint G3 Human microarrays
      8x60K were used with genomic DNA isolated from peripheral blood. Results:
      According to results of 53 patients who were included in and performed with
      arrayCGH, 8 (15%) patients had CNVs classified as pathogenic or variant of
      unknown significance (VOUS) in the study. We detected a pathogenic NRXN1 gene
      partial CNV deletion (2p16.3) in two patients. Also we identified a 900 kb
      duplication of 4p15.31 including SLIT2 gene, and a 245 kb duplication of 15q11.2
      including PWRN1 gene in one patient. Our other findings are considered to be a
      variant of unknown significance (VOUS). Conclusion: The results of the study
      support the literature knowledge, where the copy number variations that cannot be
      detected with conventional cytogenetics methods in terms of size may happen in
      patients with ASD.

PMID- 30224867
TI  - Cranial Autonomic Features in Migraine and Migrainous Features in Cluster
      Headache.
AB  - Introduction: Limited data about the importance of cranial autonomic features of
      migraines and migrainous features of cluster headaches are available. Methods: We
      enrolled 2955 patients with migraine and 93 patients with cluster headache. We
      explored the autonomic features, including ptosis, lacrimation, rhinorrhea,
      facial swelling, conjunctival injection, and pupil changes. The presence of
      migrainous features, such as nausea, vomiting, photophobia, and phonophobia, in
      cluster headache patients were noted. Results: Migraine patients with underlying
      autonomic symptoms (MwuAS) and those without differed significantly.
      Unilaterality, periocular localization of headaches provoked by starvation, and
      history of abdominal pain significantly increased the risk of MwuAS. The
      parameters with the highest sensitivity (94.38%) and specificity (99.89%) for the
      diagnosis of MwuAS were lacrimation, facial swelling, and conjunctival injection.
      Conclusion: Migraine and cluster headache are considered two different entities
      with different pathophysiologies. The assessment of autonomic symptoms is
      essential, and specialists must consider such an overlap in clinical practice in
      order to obtain accurate prevalence rates. In particular, lacrimation,
      conjunctival injection, and facial swelling are widely experienced by
      migraineurs.

PMID- 30224868
TI  - Motives and Consequences of Online Game Addiction: A Scale Development Study.
AB  - Introduction: We aimed to develop the Online Game Addiction Scale (OGAS) and
      examine its properties. Methods: Three hundred and twenty-seven secondary school
      students (92% males and 8% females) participated in this study. A draft scale
      that included 69 items was used for assessing its validity and reliability. The
      exploratory factor analysis was used for assessing construct validity, and
      Cronbach's alpha coefficient, Spearman-Brown split-half reliability, and test
      retest reliability were used for assessing reliability. Results: After performing
      the exploratory analyses, a three-factor structure comprising 21 items was
      obtained, which explained the 59% of variance. The factor loads of the items
      ranged from 0.606 to 0.876. Reliability analyses revealed that Cronbach's alpha
      coefficients ranged from 0.83 to 0.91, coefficients of the Spearman-Brown split
      half reliability ranged from 0.88 to 0.94, and outcomes of the test-retest
      reliability ranged from 0.71 to 0.94. Conclusion: Our results revealed that OGAS
      is a valid and reliable tool that has adequate psychometric properties.

PMID- 30224869
TI  - Efficacy of Diet Restriction on Migraines.
AB  - Introduction: Migraine is a common type of headache, but its pathogenesis is
      still not fully understood. Triggering factors may vary in migraine patients with
      a particular importance of certain food intake. In this study, the efficacy of
      limiting certain migraine- triggering foods in the prevention of migraine attacks
      was investigated. Methods: Patients diagnosed with migraine without aura
      according to the International Classification of Headaches were enrolled. Fifty
      migraine patients stating that migraine attack started after the intake of
      certain foods were evaluated. The patients were randomly divided into 2 groups.
      The migraine-triggering foods identified by the patients were excluded from the
      diet in both groups 1 (n=25) and 2 (n=25). Monthly attack frequency, attack
      duration, and attack severity (using the visual analogue scale) were recorded
      before starting the diet restriction and 2 months after the diet restriction.
      Diet restriction was relaxed in group 1 after the second month and continued in
      group 2. In the fourth month, the monthly attack frequency, attack duration, and
      attack severity (using the visual analogue scale) were determined in both groups.
      Results: A total of 50 patients comprising 9 males and 41 females were evaluated
      in this study. In both the groups, in the second month after diet implementation,
      monthly attack frequency, attack duration, and attack severity were found to have
      decreased to a statistically significant extent compared to those in the period
      before diet implementation [group 1 (p=0.011, p=0.041, and p=0.003, respectively)
      and group 2 (p=0.015, p=0.037, and p=0.003, respectively)]. In the evaluation in
      the fourth month, it was observed that this significant decrease was maintained
      only in group 2. Conclusion: The results of the study reveal that if migraine
      triggering foods are identified by migraine patients, restricting their intake
      can be an effective and reliable method to reduce migraine attacks.

PMID- 30224870
TI  - The validity and Reliability of the Turkish Version of Drug Attitude Inventory
      10.
AB  - Introduction: Compliance with drug treatment is an important issue in
      schizophrenia for which many scales have been devised. Turkish version of the
      Drug Attitude Inventory is frequently employed due to ease of use and high
      predictive value, although it is not as accurate as blood level testing.To
      determine the validity and reliability of the Turkish version of the Drug
      Attitude Inventory-10. Methods: Eighty-two schizophrenia patients were included
      in the study. Subjects were evaluated using Drug Attitude Inventory-10, a
      Sociodemographic Data Form, Positive and Negative Symptom Scale PANNS, Social
      Functioning Scale, and Quality of Life Scale for schizophrenia patients. Results:
      Reliability analysis revealed Cronbach's alpha coefficient for internal
      consistency to be 0.798 and item-total item correlation coefficients to be
      between 0.420 and 0.647. Test-retest correlation coefficient (r) was 0.809.
      Construct validity analysis revealed a tri-factorial construct which accounts for
      62.68% of variance. Good conformity to single factor construct was found with
      confirmatory factor analysis. Conclusion: Turkish version of the Drug Attitude
      Inventory-10 is valid and reliable for evaluation of schizophrenia patients which
      makes it suitable for research and clinical settings.

PMID- 30224871
TI  - Validity and Reliability of the Turkish Version of the Questionnaire for the
      Assessment of Dysphagia in Multiple Sclerosis.
AB  - Introduction: The aim of this study was to investigate the validity and
      reliability of the Turkish version of the Questionnaire for the Assessment of
      DYsphagia in MUltiple Sclerosis (DYMUS) that has been developed for evaluating
      dysphagia in patients with multiple sclerosis. Methods: This methodological study
      was conducted in the neurology clinic and outpatient department of a training
      hospital between March 15 and September 15, 2015. The study included 117 patients
      aged 18 years and over who had a definite diagnosis of multiple sclerosis, could
      communicate in Turkish, and volunteered to be included. Data were collected using
      a descriptive information form, the DYMUS, and the Eating Assessment Tool (EAT
      10). The scale was translated and back translated to determine the language
      validity, and a specialist was consulted to make sure the content was valid. We
      used the EAT-10 and Kurtzke's Expanded Disability Status Scale (EDSS)
      concurrently to test the criterion-related validity. The test-retest procedure
      was used at 1-week intervals for 37 patients in this study. Descriptive
      statistics, factor analysis, Kappa analysis, reliability analysis, and
      correlation analysis were used to analyze the data. Results: Factor analysis
      revealed that the scale was bifactorial, and this was consistent with its
      original form. There were positive and statistically significant relationships
      between the DYMUS and EAT-10 (r=0.90, p<0.001) and the mean EDSS scores (r=0.49,
      p<0.001). The internal consistency of the total scale was high (Cronbach's alpha
      coefficient= 0.91). The Cronbach's alpha coefficients pertaining to dysphagia for
      solids and liquids were determined to be 0.88 and 0.83, respectively. The total
      scale and subscales demonstrated a high test-retest reliability (r=0.79-0.95,
      p<0.001). Conclusion: In this study, the Turkish version of the DYMUS was found
      to be a valid and reliable tool for evaluating dysphagia in patients with
      multiple sclerosis.

PMID- 30224872
TI  - Turkish Adaptation of the Social Media Disorder Scale in Adolescents.
AB  - Introduction: The aim of this study is to determine the reliability and validity
      of the Turkish form of Social Media Disorder Scale (SMDS) in adolescents which is
      developed using the diagnostic criteria of DSM-V Internet Gaming Disorder.
      Methods: Validity and reliability analysis of SMDS was conducted through four
      different sample of 553 adolescents who use social media every day for the past 1
      year, and have at least one social media account. Results: The construct validity
      of SMDS was examined with Exploratory Factor Analysis (EFA), and Confirmatory
      Factor Analysis (CFA). After EFA, it was seen that the items of SMDS grouped
      under 1 factor which eigenvalue is above 1. This one factored structure explains
      about half of the total variance. One factored structure obtained from EFA was
      tested with CFA in two different samples. After CFA, it was shown that one
      factored SMDS model has good cohesion values in each two samples. Concurrent
      validity of the SMDS have been examined period of the use of social media, social
      media account number, self-discipline, impulsivity, positive affect, negative
      affect and social connectedness. At the result of the analysis, it was found that
      SMDS is positive correlated with duration of the use of social media, social
      media account number, negative emotions and impulsivity; negative correlated with
      self-discipline, social connectedness, and positive emotions. The reliability of
      SMDS was examined with test-retest method and Cronbach's alpha internal
      consistency reliability coefficient in three different samples. Analysis showed
      that Cronbach's alpha internal consistency reliability coefficients and test
      retest reliability coefficient were found to be adequate. SMDS item analysis was
      carried out in three different samples. It was found that corrected item-total
      correlation coefficients of the SMDS items are in the range of accepted values in
      the literature t-test results for 27% sub-super group item comparisons are
      significant for all items in each three samples. Conclusion: According to the
      results of EFA, CFA, criterion-related validity, reliability analysis, and item
      analysis of SMDS, the Turkish form of SMDS is a valid and reliable instrument.

PMID- 30224873
TI  - DSM-5 Level 2 Sleep Disorders Scale Validity and Reliability of Turkish Form
      (Form for Children Aged 11-17 Years and Parent Form for Children Aged 6-17
      Years).
AB  - Introduction: This study aimed to assess the validity and reliability of Turkish
      version of DSM-5 Level 2 Sleep Disorders Scale. Method: The scale was prepared by
      translation and back translation of DSM-5 Level 2 Sleep Disorders Scale. Study
      groups consisted of a clinical sample that contained cases that had sleep related
      problems and treated in a child and adolescent psychiatry unit and also a
      community sample. In the assessment process, child and parent forms of DSM-5
      Level 2 Sleep Disorders Scale and also Children's Sleep Habits Questionnaire
      Turkish version (CSHQ) and Pittsburgh Sleep Quality Index (PSQI) were used. As
      for reliability analyses, internal consistency coefficient and item-total score
      correlation analysis, test-retest reliability; and for validity analyses,
      explanatory factor analysis and for concurrent validity, correlation analyses
      with Children's Sleep Habits Questionnaire-Turkish version (CSHQ) and Pittsburgh
      Sleep Quality Index (PSQI) were made. Results: In reliability analyses,
      Cronbach's alpha internal consistency coefficient values were found to be very
      highly reliable regarding child and parent forms. Item-total score correlation
      coefficients were high for child form while medium and high for parent form;
      indicating a statistical significance. As for construct validity, two factors
      were maintained that would count for 74.1% of the variance in child form and
      66.9% of the variance in parent form. It was seen that positive and negative
      statements weighed on two different factors. As for concurrent validity, child
      and parent form of the scale showed significant correlation with Children's Sleep
      Habits Questionnaire-Turkish version (CSHQ) and Pittsburgh Sleep Quality Index
      (PSQI). Conclusion: It was found that Turkish version of DSM-5 Level 2 Sleep
      Disorders Scale could be utilized as a valid and reliable tool both in clinical
      practice and for research purposes.

PMID- 30224874
TI  - The Effects of the Addiction Programme of Probation on Treatment Motivation,
      Abstinence and Quality of Life: a Comparative Study with Motivational
      Interviewing and Individual Intervention.
AB  - Introduction: The aim of this study is to evaluate the effectiveness of Addiction
      Programme of Probation (APP) created by the Substance Abuse Treatment Commission
      of Ministry of Health. Methods: The sample was consisted of probationers who were
      referred to Ege University by probation offices in February 2010. Literate
      probationers aged above 18, who fulfilled the SCID-I criteria for substance
      dependence, or had positive urine sample for illegal drugs were included. The
      probationers were allocated respectively to three treatment groups: APP (n=28);
      Motivational Interviewing (MI; n=30); Individual Intervention (II; n=30). The
      effectiveness of the treatment modalities was assessed by the State Anxiety
      Inventory; the WHO Quality of Life-Brief form; the Treatment Motivation
      Questionnaire. Visual analogue and Likert-type scales were used to assess the
      sense of the importance and the readiness of quitting drugs also the levels of
      craving. Urine toxicological analyses were performed fortnightly. Results: The
      APP increased the readiness of quitting drugs. The MI increased both the sense of
      importance and readiness of quitting drugs, decreased the frequency and severity
      of craving. The II improved the mental and physical health, increased the
      confidence in treatment also readiness of quitting drugs. Additionally, II
      decreased the level of anxiety, the severity, frequency and duration of craving.
      There was a significant decrease in positive urine samples of all groups.
      Conclusion: Because of changing only "the level of being ready to quit substance
      abuse", APP is considered as an inadequate program compared with MI and II.

PMID- 30224875
TI  - The Turkish Version of Pain Assessment in Advanced Dementia (PAINAD) Scale.
AB  - Introduction: This study was conducted to test the reliability and validity of
      the Turkish version of the "Pain Assessment In Advanced Dementia (PAINAD) Scale".
      Methods: One hundred and six older adults with advanced dementia (AD) were
      recruited in the study. Detailed medical history and demographic data of the
      participants were recorded. Initially, the Turkish version of PAINAD (PAINAD-TR),
      which was prepared by means of "back-translation", was applied. Along with this
      scale, Mini Mental State Examination, Clinical Dementia Rating scale, and Visual
      Analog Scale were also used. Results: The Cronbach's alpha coefficient was 0.82
      and 0.85 for the test and re-test, respectively. For the test-retest reliability
      of the PAINAD-TR scale, values of the intraclass correlation coefficient (ICC)
      and 95% confidence interval (CI) were 0.812 and 0.763-0.850 respectively.
      According to the results of a factor analysis carried out on the scale, a 2
      domain structure was proved. Conclusion: The PAINAD-TR scale can be used for the
      assessment and management of pain in non-communicative older adults with AD.

PMID- 30224876
TI  - A SOD2 Polymorphism is Associated with Abnormal Quantitative Sensory Testing in
      Type 2 Diabetic Patients.
AB  - Introduction: Diabetes mellitus (DM) affects peripheral nerves inducing diabetic
      polyneuropathy (DPN). Mitochondrial dysfunction and oxidative stress are
      potential causes of DPN. Methods: Nerve conduction studies were performed in 20
      type 2 DM patients (11 with DPN) and 15 healthy controls. Perception threshold
      values of cold, warm and vibration were measured by quantitative sensory testing.
      Variants of a superoxide dismutase 2 (SOD2) gene single nucleotide polymorphism
      (SNP) (rs5746136) were determined by polymerase chain reaction (PCR) and
      following NexteraXT DNA Library. Results: DPN patients showed significantly
      increased threshold values. DM patients without DPN and healthy controls showed
      comparable values. TT variant of the SOD2 SNP was more prevalent in DM and DPN
      patients. DM patients with the TT variant displayed increased perception
      threshold values. Conclusions: Quantitative sensory testing is not superior to
      standard nerve conduction studies in DPN. Carriers of SOD2 SNP manifested
      increased sensory threshold levels which is important in further corroborating
      the link between oxidative stress and DPN.

PMID- 30224878
TI  - Fabry Disease Diagnosis in a Young Stroke Patient: A Case Report.

PMID- 30224879
TI  - The real life data of ranibizumab use among the diabetic macular edema patients
      in Turkey: Documenting the improvement with clinical optimization during three
      consecutive years.
AB  - Purpose: To report the 12 month real life outcomes of ranibizumab treated
      diabetic macular edema (DME) patients. Methods: Treatment naive DME patients
      treated with ranibizumab were included. Patients were divided into three groups
      according to their hospital admittance years (2013, 2014, and 2015) and were
      compared in regards to the treatment outcomes. Results: The mean visual acuity
      change from baseline to month 12 was not statistically significant in 2013 at
      month 12. The mean BCVA change from baseline to month 12 was statistically better
      at month 12 in 2014 and 2015. There was a statistically significant difference
      among the three groups in regards to both mean visit and injection numbers. The
      mean visit number in 2013 and 2014 were both lower than 2015. The mean injection
      number in 2013 was lower than both 2014 and 2015. Conclusions: It is effortful to
      obey the strict follow-up criteria of prospective studies in DME patients on a
      PRN regimen. However, optimizing the clinical processes of patient management may
      lead to improved clinical outcomes in real life.

PMID- 30224877
TI  - Suggested Biomarkers for Major Depressive Disorder.
AB  - Currently, the diagnosis of major depressive disorder (MDD) mainly relies on
      clinical examination and subjective evaluation of depressive symptoms. There is
      no non-invasive, quantitative test available today for the diagnosis of MDD. In
      MDD, exploration of biomarkers will be helpful in diagnosing the disorder as well
      as in choosing a treatment, and predicting the treatment response. In this
      article, it is aimed to review the findings of suggested biomarkers such as
      growth factors, cytokines and other inflammatory markers, oxidative stress
      markers, endocrine markers, energy balance hormones, genetic and epigenetic
      features, and neuroimaging in MDD and to evaluate how these findings contribute
      to the pathophysiology of MDD, the prediction of treatment response, severity of
      the disorder, and identification of subtypes. Among these, the findings related
      to the brain-derived neurotrophic factor, the hypothalamo-pituitary-adrenal axis,
      cytokines, and neuroimaging may be strong candidates for being biomarkers MDD,
      and may provide critical information in understanding biological etiology of
      depression. Although the findings are not sufficient yet, we think that the
      results of epigenetic studies will also provide very important contributions to
      the biomarker research in MDD. The availability of biomarkers in MDD will be an
      advancement that will facilitate the diagnosis of the disorder, treatment choices
      in the early stages, and prediction of the course of the disorder.

PMID- 30224881
TI  - Intra-correlations between cataract density based on Scheimpflug image,
      phacodynamics, surgery duration, and endothelial cell loss after
      phacoemulsification.
AB  - Purpose: To assess intra-correlations between lens density based-on Scheimpflug
      Imaging System, power used during surgery, surgery duration, and endothelial cell
      loss in eyes with nuclear cataract. Setting: Department of Ophthalmology, King
      Fahd Hospital of the University, Alkhobar, Saudi Arabia. Design: Prospective
      cross-sectional observational study. Methods and material: The objective lens
      density and endothelial cell density were measured using the Scheimpflug system
      and specular microscopy, respectively. Intra-operatively, all phacodynamic
      parameters and duration of the surgery were documented. Results: This study of 62
      patients (71 eyes) with a mean age of 58.56 +/- 10.4 years. The mean Scheimpflug
      measured lens density was 13.93 +/- 3.27. The mean phacodynamic parameters,
      namely, power, ultrasound time, and elliptical motion were 13.63 +/- 6.38, 1.27
      +/- 1.12, and 50.56 +/- 50.06, respectively. There were a positive linear
      correlations between the Scheimpflug-measured lens density and phacodynamic
      parameters, power (AVG %), ultrasound time, and elliptical motion (r = 0.501, r =
      0.620, and r = 0.641, respectively; all P < .001), amount of endothelial loss (r
      = 0.445, P < .001), and surgery duration (r = 0.346; P < .01). Phacodynamic
      parameters were positively correlated with degree of endothelial loss (P < .01).
      The length of the surgery failed to show any correlation with damage happened to
      the endothelium (r = 0.210, P > .05). Conclusion: A positive correlations were
      observed between Scheimpflug-measured lens density with phacodynamic parameters,
      surgery duration, and endothelial loss. A strong correlation was observed between
      the degree of endothelial cell loss and phacodynamic parameters but not with the
      length of the procedure.

PMID- 30224880
TI  - Vitrectomy combined with posterior-segment Ahmed valve implant: A case series
      study.
AB  - Purpose: To analyze the surgical outcomes and complication rates in a group of
      patients with refractory glaucoma who underwent simultaneous pars plana
      vitrectomy (PPV) and PC7 or PC8 Ahmed glaucoma valve (AGV) implantation. Methods:
      Retrospective case series study of 10 eyes in 9 patients with secondary glaucoma,
      refractory to other treatment, who underwent 23G-PPV and implantation of PC7 or
      PC8 AGV between 2012 and 2014. Study variables were postoperative BCVA, IOP and
      the number of glaucoma medications, which were evaluated preoperatively and at 1
      day, 1 week and 1, 3, 6, and 12 months after the surgical intervention. Absolute
      success was defined as IOP less than 21 mmHg in the absence of any medication and
      qualified success if medication was needed to control IOP under 21 mmHg. Results:
      The average follow-up was 10.2 +/- 2.89 months. Postoperative IOP levels
      decreased in all cases in comparison with preoperative values (p < 0.05).
      Absolute success rate was 60%, reaching 100% in terms of qualified success.
      Kaplan-Meier survival analysis showed 60% absolute success at 12 months. Changes
      in postoperative BCVA were not statistically significant in comparison with
      preoperative data. Early postoperative complications were athalamia, hyphema, and
      retinal detachment; late complications were pars plana clip extrusion and cystic
      bleb. Conclusions: PC7 and PC8 Ahmed valve implantation via pars plana is a safe
      and useful option in patients with secondary refractory glaucoma who are either
      candidates for PPV or have been previously vitrectomized.

PMID- 30224882
TI  - Measurement of anterior segment parameters in Saudi adults with myopia.
AB  - Purpose: To measure anterior segment parameters of the eye in myopic Saudi
      population using Pentacam. Method: This is retrospective cross-sectional study.
      Subjects were divided into three groups: low, moderate and high myopia groups.
      Anterior segment parameters including: central corneal thickness (CCT), thinnest
      corneal thickness (TCT), apex corneal thickness (Apex CT), corneal volume (CV),
      anterior chamber depth (ACD), anterior chamber volume (ACV) and corneal
      astigmatism (CA) were measured by Pentacam. Results: A total of 504 eyes of 252
      Saudi subjects with myopia were included in this study. The mean age +/- standard
      deviation (SD) of subjects was 28.73 +/- 6.18 years. The mean CCT, TCT, Apex CT,
      CV, ACD, ACV and CA for all myopic subjects were 557.21 +/- 29.36, 554.09 +/-
      29.28, 556.10 +/- 37.06, 61.30 +/- 3.23 MUm, 3.31 +/- 0.27 mm, 211.15 +/- 34.22
      mm3 and 0.89 +/- 0.52 D, respectively. No significant differences (P > 0.05) were
      found between right and left eyes in all anterior segment parameters of all
      myopic eyes. However, a significant difference (P < 0.05) was found in ACD
      between low (3.27 +/- 0.26 mm) and moderate (3.35 +/- 0.30 mm) myopic groups.
      Within low myopia group, significant differences (P < 0.05) were found in ACD,
      ACV and CA between different genders. Anterior chamber depth and ACV values were
      lower in females while CA was lower in males. In addition, significant positive
      correlation was found between ACV and ACD in all myopic groups. Conclusion: This
      study provided valuable measurements of the anterior segments parameters of the
      eye in myopic Saudi population. These parameters could be useful for ophthalmic
      practitioners in the clinic.

PMID- 30224883
TI  - The use of one muscle recession for horizontal strabismus.
AB  - Purpose: To evaluate the outcomes of one muscle recession for horizontal comitant
      strabismus at a major referral hospital in the Middle East. Method: Retrospective
      charts review of postoperative outcomes of 90 patients who had undergone one
      muscle recession for small to moderate angle esotropia or exotropia. Data were
      collected for age, vision, amblyopia, previous surgery or botulinum toxin
      injection, preoperative deviation, amount and type of one muscle surgery, and
      postoperative deviation at the initial and last (six months or more)
      postoperative visit. Successful alignment was defined as +/-10 prism diopters
      (PD) of orthophoria. Results: Sixty patients underwent medial rectus recession
      and 30 patients underwent lateral rectus recession. The average preoperative and
      last follow up deviation -respectively- was 24 +/- 6.1 PD (15-35) PD and 14.62 +/
      8.91 PD in the medial rectus recession group and 21.3 +/- 5.1 PD (12-30) and
      12.60 +/- 8.74 in the lateral rectus recession group. The final success rates
      were 63.3% in both groups. Conclusion: Single muscle strabismus surgery to
      correct horizontal strabismus had a variable outcome. Larger recession may help
      in achieving better outcomes. Properly designed prospective studies may help in
      identifying the factors affecting the outcomes of single muscle strabismus
      surgeries.

PMID- 30224884
TI  - Does the addition of hyaluronidase improve the quality of peribulbar anesthesia
      in cataract surgery? - A randomized double blinded study.
AB  - Purpose: To determine the necessity of hyaluronidase as an anesthetic adjuvant
      for peribulbar anesthesia during cataract surgery and to assess differences in
      anesthetic outcomes in the absence of hyaluronidase. Methods: In this double
      blinded randomized study, 202 patients reporting for surgery for senile cataract
      in their first eye under regional ocular anesthesia without pre-existing extra
      ocular movement restriction were randomly divided into 2 groups: Group 1 -
      anesthesia without hyaluronidase, Group 2 - anesthesia with 50 IU/ml
      Hyaluronidase. Peribulbar block with 5 ml of anesthetic mixture of 2% lignocaine
      with 1:200000 adrenaline and 0.5% bupivacaine with or without hyaluronidase was
      performed with 3 ml deposited in the infero-medial quadrant and 2 ml in the
      supero-medial quadrant followed by ocular massage. Surgeons' score for akinesia,
      patients' score for analgesia, augmentation of block if any and extra ocular
      movements on first post-operative day were compared between the groups. Results:
      There was no statistically significant difference between the two groups in
      akinesia (p = 0.22, 0.68 and 0.98), analgesia (p = 0.44 and 0.09) or requirement
      of anesthetic augmentation (p = 0.3). Extraocular movement restriction was not
      noted in any patient. Onset of akinesia and analgesia was earlier in Group 2 (p =
      0.004 and p = 0.005 respectively). Conclusions: Hyaluronidase is not an essential
      adjuvant for peribulbar block for cataract surgeries. Appropriate deposition of a
      smaller volume of anesthetic agent and adequate ocular massage provide adequate
      and safe anesthesia.

PMID- 30224885
TI  - Assessment of visual function and Vision-related Quality of Life in female
      contact lens wearers with Dry Eye Syndrome.
AB  - Purpose: To assess visual function and Vision-related Quality of Life (VRQOL) in
      female contact lens wearers with Dry Eye Syndrome in Riyadh city, Saudi Arabia.
      Methods: This was a cross sectional study. Saudi Females subjects with and
      without DES (contact lens wearer [CLW] and Non-contact lens wearers [NCLW]) aged
      between 16 and 35 years were included in this study. Subjects were recruited from
      female campus at King Saud University (KSU), Riyadh, KSA. Measurements include
      corneal topography, visual acuity (VA), autorefraction, contrast sensitivity
      (CS), Schirmer's test and Tear breakup test (TBUT) were performed on all
      subjects. In addition, corneal thickness was measured using Pentacam HR to
      compare between the total corneal thickness (TCT) in DES and Non-DES groups.
      Contact Lens Impact on Quality of Life (CLIQ) Questionnaire was used to assess
      VRQOL. Visual functions and VRQOL were compared between groups (contact lens (CL)
      and NCLW) using SPSS program version 23 (SPSS Inc, Chicago, Illinois, USA).
      Results: A total of 100 subjects with DES (n = 44 including 25 CLW and 19 NCLW),
      and non-DES (n = 56 including 17 CLW and 39 NCLW) were included in this study.
      The mean age of participants with DES was 21.39 years and was 20.96 years of
      participants Non-DES. There were no significant different in VA, CS, and TCT
      between subjects DES and Non-DES (P > 0.05), which indicates that dryness have no
      effect on the visual function and TCT. Contact lens wearers had higher score on
      convince, economic and psychological items than NCLW. Within CL group, subjects
      with DES had higher score on convince and psychological items. Similarly, within
      DES group, subjects who wore CL had higher score on convince and psychological
      items. Conclusion: This study provides evidence that dryness may has no effect on
      visual function in both CLW and NCLW. Psychological and convenience domains of
      VRQOL were negatively affect in Saudi female patients with DES specially who wear
      CL.

PMID- 30224886
TI  - Efficacy and safety of using topical cyclosporine A for treatment of moderate to
      severe dry eye disease.
AB  - Objective: To investigate and evaluate the efficacy and safety of topical
      cyclosporine A for treatment of moderate to severe dry eye disease. Materials and
      methods: This is a prospective study of patients with moderate to severe dry eye
      syndrome were recruited. All cases were selected from patients attending the
      ophthalmic outpatient clinic of Research institute of ophthalmology. Eligible
      patients were at least 21 years of age with a confirmed diagnosis of
      keratoconjunctivitis sicca with or without Sjogren's syndrome refractory to
      conventional management.The medication used in this study were unit dose vials of
      unpreserved cyclosporine A 0.05% used twice daily.The protocol was composed of a
      2-week washout phase, a 12-week treatment phase, and a 4-week post treatment
      phase. Patients were evaluated at weeks 4, 8, 12 during the treatment phase.
      During these visits patients were evaluated for changes from base line in
      Schirmer test, rose Bengal staining, superficial punctuate erosions, BUT,
      impression cytology, symptoms of ocular discomfort and visual acuity. After
      completion of the treatment phase, patients were also evaluated at post treatment
      week 4, during this visit patients were assessed for Schirmer test, rose Bengal
      staining, superficial punctuate erosion, BUT, impression cytology, symptoms of
      ocular discomfort and visual acuity. Results: Thirty two cases in the mean age of
      47 (12.9), range [20-67] years; four (13%) male and 28 (87%) female were
      recruited in the current study. Out of them, 12 (38%) cases had Sjogren syndrome.
      Visual acuity improved significantly (p = 0.012), BUT (p < 0.0001) for both eyes,
      Schirmer measurements (p < 0.0001 and p = 0.029 for OD and OS, respectively).
      Conclusions: Cyclosporine A ophthalmic emulsion 0.05% has been demonstrated to be
      effective and safe in human clinical trials. It reduces signs and symptoms of dry
      eye disease, with the fact that its effect continued to occur significantly
      within the treatment periods as well as improvement of ocular condition kept on,
      actually more slowly towards stability, despite the drug has already stopped.

PMID- 30224887
TI  - Practical guidelines for screening and treatment of retinopathy of prematurity in
      Saudi Arabia.
AB  - Retinopathy of Prematurity (ROP) is one of the leading causes of bilateral
      blindness in childhood. Early detection and effective treatment can prevent
      blindness. Efficient and timely screening examination of the retina by an
      experienced ophthalmologist who deals with preterm neonates with ROP is the
      mainstay in the management of this disease. All neonatologists and pediatricians
      who care for these at-risk preterm neonates should also be aware of this timing.
      This practical guideline intends to provide guidance to ophthalmologists,
      neonatologists and allied health care professionals in Saudi Arabia on current
      indications for screening and management of retinopathy of prematurity to prevent
      or minimize subsequent complications. This practical guideline was led by the
      National Eye Health Program (NEHP) and Neonatology Services Improvement Program
      at Ministry of Health (MOH), furthermore it has been solicited and endorsed from
      both Saudi Ophthalmological Society (SOS) and Saudi Neonatology Society (SNS).

PMID- 30224888
TI  - Water related ocular diseases.
AB  - A number of ocular diseases can be attributed to contaminated water and we have
      coined a term "Water-related ocular diseases (WRODs)" to denote this wide
      spectrum of conditions. WRODs are directly related to human contact with water
      and can occur through toxic, allergic, inflammatory or infective mechanisms. The
      non-infective causes can include chemicals used to clean swimming pools, oil
      spills and water-sport related injuries. Similarly, a number of infective
      organisms causing ocular diseases are transmitted through water. Since, these
      conditions can occasionally prove devastating, a review was done with the
      following aims: (i) To study the epidemiology of WRODs (ii) To assess the
      clinical presentation and current management of WRODs (iii) To highlight the
      future challenges and possible solutions to these problems. The online search was
      conducted utilizing search engines such as PubMed, Google Scholar, ClinicalKey
      and the Virtual Library of the Ministry of Health, Malaysia for relevant terms
      such as water-borne, swimming pool and eye infections.

PMID- 30224889
TI  - Combined cilioretinal artery and hemi-retinal vein occlusion in Sturge Weber
      syndrome: Expanding the clinical spectrum.
AB  - A 9-year-old boy with the diagnosis of Sturge-Weber Syndrome, and port-wine stain
      involving the right side of the face, presented with acute visual loss of the
      right eye. Examination revealed a high intraocular pressure and a combined
      cilioretinal artery and inferior hemi-retinal vein occlusion in the right eye.
      Systemic work-up was negative. After controlling the intraocular pressure,
      gradual improvement of vision was noticed with simultaneous disappearance of
      signs of vascular occlusion.

PMID- 30224890
TI  - Non-axial proptosis secondary to pneumosinus dilatans of the maxillary sinus.
AB  - Pneumosinus Dilatans (PD) is a rare condition characterized by abnormal
      enlargement of one or more paranasal sinuses that can lead to different
      functional and cosmetic presentations. Here we report right non-axial proptosis
      in a 47-year-old female secondary to pneumosinus dilatans of the maxillary sinus
      with superior bowing of the orbital floor.

PMID- 30224891
TI  - A clinical case of Zellweger syndrome in a patient with a previous history of
      ocular medulloepithelioma.
AB  - Peroxisomal biogenesis disorders (PBDs) are autosomal recessive diseases caused
      by mutations in one of the 14 PEX genes described in the scientific literature.
      All of these syndromes may be associated with different mutations in the PEX
      genes, the most frequent being PEX1 for patients with Zellweger syndrome (ZS). In
      this paper, we present the case of a patient with a peculiar clinical history:
      evisceration of the left eye (LE) at 4 years of age because of a benign ocular
      teratoid medulloepithelioma and a progressive loss of visual acuity (VA) in the
      right eye (RE) beginning at 9 years of age, leading to the diagnosis of ZS. In
      addition, the patient presented a mutation in the PEX14 gene that has not been
      previously described in the literature. This case broadens the spectrum of
      clinical expression in ZS patients because of not only the presence of a benign
      ocular teratoid medulloepithelioma at 4 years of age but also the late clinical
      expression of ZS (at 9 years of age).

PMID- 30224892
TI  - A healthy infant with bloody tears: Case report and mini-review of the
      literature.
AB  - A 4-month old healthy infant was brought by her parents to the emergency
      department with bloody tears of three days duration. There was also intermittent
      yellowish discharge since birth and a history of flu-like symptoms a week prior
      to presentation. Extensive investigations revealed no infection or other possible
      etiologies. The patient was treated with antibiotic eye drops and her condition
      resolved within a three-four days. In the literature, 15 cases with haemolacria
      of undermined source were reviewed; the median age of onset (12 years), bilateral
      involvement and female gender were more commonly encountered, and the most common
      associated illnesses were headache and epistaxis. The condition is self-limiting
      and spontaneous resolution is seen in majority of cases. Idiopathic haemolacria
      is a rare condition that can be presumed in patients presenting with bloody tears
      when all work-up turns to be negative. The condition is self-limiting with
      spontaneous resolution.

PMID- 30224893
TI  - Ophthalmomyiasis externa: A case report from Alkharj, Saudi Arabia.
AB  - Ophthalmomyiasis is an infestation of mammalian eyes with larvae or maggots of
      certain flies. Oestrus ovis is the most common cause of human myiasis. This
      article reports a case of ophthalmomyiasis externa caused by Oestrus ovis (sheep
      nasal botfly) in a young healthy male, living in Al Kharj, Kingdom of Saudi
      Arabia. Patient presented with acute symptoms in left eye in April, mimicking as
      unilateral conjunctivitis/keratitis/external ocular foreign body/uveitis. Prompt
      diagnosis and mechanical removal of five live larvae from conjunctival fornices
      of the left eye under topical anaesthesia and cyclopentolate 1% eyedrops, not
      only relieved patient's severe symptoms in a single day but also prevented rare
      yet sight threatening complications.

PMID- 30224894
TI  - Acute lacrimal gland swelling with intracranial extension and without any
      neurological features - A rare case report.
AB  - We report a case of young adult female with swelling in the superolateral aspect
      of left orbit for two weeks which was diagnosed as tubercular dacryoadenitis with
      intracranial extension without any neurological features. Tubercular
      dacryoadenitis is very rare but still makes an important differential diagnosis
      of lacrimal gland swellings especially in endemic areas like India. Few cases of
      tubercular dacryoadenitis have been reported in the past; but not a single case
      with intracranial extension in young adults with short history and without
      neurological symptoms. Although radiological investigations are routinely done in
      orbital lesions, it is advisable do so even in acute cases to look for
      intracranial extension before the appearance of neurological features. Tubercular
      dacryoadenitis though rare, should be kept as a differential diagnosis of acute
      or chronic lacrimal gland swellings in endemic areas.

PMID- 30224895
TI  - Displacement of crystalline lens into the sub-conjunctival space following
      periocular anesthesia.
AB  - A 65-year-old female presented with loss of vision and a mass in her right eye
      after periocular anaesthesia for cataract surgery in a camp. She was found to
      have a nasal subconjunctival mass, which was confirmed to contain the crystalline
      lens after surgical exploration, along with a superior perilimbal suspected
      scleral rupture. There was accompanying vitreous haemorrhage, retinal detachment
      and subretinal haemorrhage that was managed by pars plana vitrectomy. Post
      operatively, she achieved a best corrected visual acuity of 20/80 that was
      maintained till 6 months follow up. Globe rupture and subconjunctival lens
      extrusion in the setting of inadvertent globe penetration during periocular
      anesthesia is a rare complication. In the absence of medical records pertaining
      to the primary event, this clinical presentation posed a diagnostic challenge.
      Timely and appropriate management led to an acceptable visual and anatomical
      outcome in this unfortunate and devastating scenario.

PMID- 30224896
TI  - Fungal endophthalmitis in a case of granulomatosis with polyangitis.
AB  - A 70-year-old immuno-compromised man, due to multiple comorbidities, particularly
      granulomatosis with polyangitis (GPA) and its related treatment, presented with
      generalized weakness, odynophagia and loss of taste sensation. After a complete
      evaluation, a diagnosis of right frontal lobe brain abscess was made. The patient
      then developed headache and sudden painful loss of vision in the right eye.
      Clinical examination revealed anterior chamber cells and flare, vitreous haze and
      cells, and hemorrhagic chorioretinitis with severe vasculitis in the right eye.
      Culture from the drained pus of the frontal brain abscess came positive for
      Aspergillus fumigatus. Incidental echocardiogram showed large vegetation in the
      mitral valve. Pars plana vitrectomy was done and a specimen was sent for culture
      that came positive for Aspergillus fumigatus. Although all the necessary medical
      and surgical interventions were timely carried out in the affected right eye, the
      patient's vision worsened due to retinal damage.

PMID- 30224897
TI  - Circumpunctal nevus.

PMID- 30224898
TI  - Erratum to "Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II
      Induced Cardiac Hypertrophy in Mice".
AB  - [This corrects the article DOI: 10.1155/2017/5635929.].

PMID- 30224899
TI  - Icaritin Provokes Serum Thrombopoietin and Downregulates Thrombopoietin/MPL of
      the Bone Marrow in a Mouse Model of Immune Thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is a common acquired autoimmune disease, and
      thrombopoietin (TPO) is an important cytokine that regulates the production of
      megakaryocytes and platelets. We have identified a biologically active component,
      icaritin, from a Chinese herba epimedii extract. Icaritin promotes platelet
      production and regulates T cell polarization, but its mechanism is not clear. In
      this study, the BALB/c mouse model of ITP was established by injection of an
      antiplatelet antibody every other day for seven total times. The antiplatelet
      sera were derived from guinea pigs immunized with the platelets of BALB/c mice.
      Mice with ITP were treated with icaritin at low, moderate, or high doses of 4.73,
      9.45, and 18.90 mg/kg, respectively, for fourteen consecutive days. The present
      study shows that icaritin can significantly increase peripheral blood platelet
      counts and thrombocytocrit, increase the TPO level in serum, attenuate
      splenomegaly, and reduce the abnormal proliferation of megakaryocytes in the
      spleen and bone marrow. Icaritin can also downregulate the expression of bone
      marrow TPO, myeloproliferative leukemia virus oncogene (MPL), and p-Stat3. Our
      results suggest that icaritin can significantly improve the health of mice with
      ITP via possible downregulation of p-Stat3 expression in the JAK2/Stat3
      phosphorylation signaling pathway and regulation of bone marrow TPO/MPL
      metabolism.

PMID- 30224901
TI  - Synchronous prostate and rectal cancer, a case report.
AB  - The incidence of multiple primary neoplasms has been increasing over the years.
      Within this group, the coexistence of primary prostate cancer and primary
      colorectal cancer is one of the most frequent. The objective of this case report
      is to present the case of a 76-year-old male patient who presented the diagnosis
      of prostate cancer and synchronous rectal cancer. To this end, his clinical
      history in the oncological service of the Hospital Militar Central del Peru
      (tertiary hospital) has been reviewed.

PMID- 30224900
TI  - Role of Histamine in Modulating the Immune Response and Inflammation.
AB  - Inflammatory mediators, including cytokines, histamine, bradykinin,
      prostaglandins, and leukotrienes, impact the immune system, usually as
      proinflammatory factors. Other mediators act as regulatory components to
      establish homeostasis after injury or prevent the inflammatory process.
      Histamine, a biogenic vasoactive amine, causes symptoms such as allergies and has
      a pleiotropic effect that is dependent on its interaction with its four histamine
      receptors. In this review, we discuss the dualistic effects of histamine: how
      histamine affects inflammation of the immune system through the activation of
      intracellular pathways that induce the production of inflammatory mediators and
      cytokines in different immune cells and how histamine exerts regulatory functions
      in innate and adaptive immune responses. We also evaluate the interactions
      between these effects.

PMID- 30224902
TI  - Physicochemical and Microbiological Quality of Dietetic Functional Mixed Cerrado
      Fruit Jam during Storage.
AB  - The objective of the research was to evaluate changes of dietetic functional
      mixed cerrado fruit jam (marolo, sweet passion fruit, and soursop) processed in a
      vacuum pot and stored for 180 days in BODs at 25 degrees C and 35 degrees C. The
      parameters evaluated were pH, soluble solids (SS), titratable acidity (TA), total
      sugars (TS), total carotenoids (TC), total phenolics (TP), vitamin C, antioxidant
      activity (DPPH), and microbiological analysis. There was a significant effect of
      storage time on pH, SS, TA, TC, TS, and TP. Vitamin C and DPPH showed an effect
      for the temperature x storage time interaction. Statistical models are not
      adjusted for pH and SS, presenting an average of 4.15 and 61%, respectively.
      Carotenoids decreased up to105 days; total sugars increased up to 105 days. The
      TP, vitamin C, and DPPH, at the temperatures evaluated, showed a decrease up to
      105 days. Yeasts and filamentous fungi were not detected.

PMID- 30224903
TI  - Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications.
AB  - Molecular imaging is an emerging strategy for in vivo visualization of cancer
      over time based on biological mechanisms of disease activity. Optical imaging
      methods offer a number of advantages for real-time cancer detection, particularly
      in the epithelium of hollow organs and ducts, by using a broad spectral range of
      light that spans from visible to near-infrared. Targeted ligands are being
      developed for improved molecular specificity. These platforms include small
      molecule, peptide, affibody, activatable probes, lectin, and antibody.
      Fluorescence labeling is used to provide high image contrast. This emerging
      methodology is clinically useful for early cancer detection by identifying and
      localizing suspicious lesions that may not otherwise be seen and serves as a
      guide for tissue biopsy and surgical resection. Visualizing molecular expression
      patterns may also be useful to determine the best choice of therapy and to
      monitor efficacy. A number of these imaging agents are overcoming key challenges
      for clinical translation and are being validated in vivo for a wide range of
      human cancers.

PMID- 30224904
TI  - MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management.
AB  - Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest
      cancers for which optimal diagnostic tools are still greatly needed.
      Identification of PDAC-specific molecular markers would be extremely useful to
      improve disease diagnosis and follow-up. MT1-MMP has long been involved in
      pancreatic cancer, especially in tumour invasion and metastasis. In this study,
      we aim to ascertain the suitability of MT1-MMP as a biomarker for positron
      emission tomography (PET) imaging. Two probes were assessed and compared for this
      purpose, an MT1-MMP-specific binding peptide (MT1-AF7p) and a specific antibody
      (LEM2/15), labelled, respectively, with 68Ga and with 89Zr. PET imaging with both
      probes was conducted in patient-derived xenograft (PDX), subcutaneous and
      orthotopic, PDAC mouse models, and in a cancer cell line (CAPAN-2)-derived
      xenograft (CDX) model. Both radiolabelled tracers were successful in identifying,
      by means of PET imaging techniques, tumour tissues expressing MT1-MMP although
      they did so at different uptake levels. The 89Zr-DFO-LEM2/15 probe showed greater
      specific activity compared to the 68Ga-labelled peptide. The mean value of tumour
      uptake for the 89Zr-DFO-LEM2/15 probe (5.67 +/- 1.11%ID/g, n=28) was 25-30 times
      higher than that of the 68Ga-DOTA-AF7p ones. Tumour/blood ratios (1.13 +/- 0.51
      and 1.44 +/- 0.43 at 5 and 7 days of 89Zr-DFO-LEM2/15 after injection) were
      higher than those estimated for 68Ga-DOTA-AF7p probes (of approximately
      tumour/blood ratio = 0.5 at 90 min after injection). Our findings strongly point
      out that (i) the in vivo detection of MT1-MMP by PET imaging is a promising
      strategy for PDAC diagnosis and (ii) labelled LEM2/15 antibody is a better
      candidate than MT1-AF7p for PDAC detection.

PMID- 30224905
TI  - 7-Isopenthenyloxycoumarin, Arctigenin, and Hesperidin Modify Myeloid Cell
      Leukemia Type-1 (Mcl-1) Gene Expression by Hormesis in K562 Cell Line.
AB  - Hormesis is a new concept in dose-response relationship. Despite of traditional
      dose-response curves, there is a low-dose stimulation and a high-dose inhibition
      in this case. Hormesis effect in apoptosis induction/inhibition by natural
      compounds is reported previously. Here, we searched this effect for myeloid cell
      leukemia type-1 (Mcl-1) gene expression by phytochemicals 7
      isopenthenyloxycoumarin (7-IP), arctigenin (Arg), and hesperidin (Hsp). For this
      purpose, first we tested the cytotoxicity of various doses of these compounds
      against K562 leukemia cell lines for different times by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide method. After that we explored the effect of
      various doses of these phytochemicals on Mcl-1 gene expression for different
      times by real-time polymerase chain reaction method. We found that these
      phytochemicals have cytotoxicity against K562 cell line. Hesperidin is the most
      cytotoxic agent. We also found that these natural compounds have hormetic effect
      on Mcl-1 gene expression. The hormetic model in Mcl-1 gene expression is
      overcompensation stimulation. This phenomenon is reported for the first time. We
      conclude that 7-IP, Arg, and Hsp are cytotoxic against K562 cancerous cells and
      induce/inhibit Mcl-1 gene expression by hormesis dose-response relationship.

PMID- 30224906
TI  - An Outbreak of Scombroid Fish Poisoning Associated with Consumption of Yellowtail
      Fish in Seoul, Korea.
AB  - Background: In November 2016, an outbreak of scombroid fish poisoning occurred
      among elementary school students in Seoul, Korea. An epidemiological
      investigation was conducted to identify the cause and source of the illness.
      Methods: A case-control study was conducted among school members who had eaten
      lunch in the school. The histamine level in the suspect food item (yellowtail
      steak) was measured. Results: Fifty-five (5.4%) of 1,017 school members who
      consumed fish for lunch fell ill. The principal symptoms were flushing (100%) and
      headache (72.7%); the median incubation period was 40 minutes. All had consumed
      yellowtail steak (odds ratio, 9.24; 95% confidence interval, 1.22-69.91).
      Leftover steak had an elevated histamine level (293 mg/kg), higher than the
      allowed 200 mg/kg. Conclusion: An outbreak of scombroid fish poisoning was
      confirmed; this is the first such report in Korea. Detailed food safety
      guidelines must be established.

PMID- 30224907
TI  - Clinical Usefulness of Unenhanced Computed Tomography in Patients with Acute
      Pyelonephritis.
AB  - Background: Unenhanced computed tomography (UCT) may be useful for evaluating
      acute pyelonephritis; however, no study has compared UCT with enhanced computed
      tomography (ECT) as a diagnostic tool. We evaluated a clinical usefulness of UCT
      versus ECT in acute pyelonephritis (APN). Methods: We reviewed the clinical and
      radiological data from 183 APN-suspected patients who underwent UCT and ECT
      simultaneously at emergency room (ER) over a two-year period. Demographic,
      clinical parameters and computed tomography (CT) parameters of 149 patients were
      compared. Results: The average patient age was 61.2 (+/- 10) years: 31 patients
      were men. Ninety-nine (66.4%) patients showed stones (18.7%), perinephric
      infiltration (56%), swelling (21%), and hydronephrosis (6.7%) on UCT. Seventeen
      patients (11.4%) had an atypical clinical course, requiring additional tests for
      accurate diagnosis. In 7 patients UCT and ECT results did not differ; in 10
      patients, the diagnosis changed on ECT. On ECT, 112/149 (75.2%) patients had
      stones (16.7%), perinephric infiltrations (57%), swelling (21%), and
      hydronephrosis (6.7%); 62.5% showed parenchymal involvement: 34 (22.8%) patients
      had no abnormal ECT findings. APN CT findings are similar on stone, perinephric
      infiltration, swelling and hydronephrosis on both CTs. Twelve patients (8.0%) had
      an abnormal ECT finding, i.e., low-grade (1 and 2) parenchymal involvement. Six
      (4%) patients developed contrast-induced acute kidney injury within 2 days after
      ECT. Conclusion: We demonstrate that UCT is not inferior to ECT as an initial
      tool for evaluating APN for screening nephrolithiasis and hydronephrosis without
      the risk of contrast-induced acute kidney injury (CIAKI). However, patients with
      an atypical clinical course may still need ECT.

PMID- 30224908
TI  - Long-term Outcomes of Endoscopic Anti-reflux Surgery in Pediatric Patients with
      Vesicoureteral Reflux: Urinary Tract Infection, Renal Scarring, and Predictive
      Factors for Success.
AB  - Background: To report the long-term outcomes of endoscopic surgery (ES) in
      pediatric patients with vesicoureteral reflux in terms of success rate, urinary
      tract infection, and renal function. Methods: We retrospectively reviewed the
      records of 73 pediatric patients (110 ureters) who underwent ES for
      vesicoureteral reflux. Ultrasonography was performed 1, 3, and 12 months
      postoperatively. Voiding cystourethrography was performed 3 months
      postoperatively and repeated after 1 year if vesicoureteral reflux persisted.
      Success was defined as the absence of reflux at the first voiding
      cystourethrography. Renal scans were performed at least 12 months
      postoperatively. Renal function deterioration was defined as a new scar or a
      greater than 5% decrease in function. Results: The median follow-up duration was
      24 (12-118) months. The overall success was 65.6%, while it was 78.9%, 87.0%,
      62.5%, 37.5%, 66.7% for grades I, II, III, IV, and V, respectively. In
      multivariate analyses, significant predictive factors for success were
      vesicoureteral reflux grade (odds ratio [OR], 0.28; P < 0.001) and mound
      detection at the first postoperative ultrasonography (OR, 13.53; P < 0.001).
      Renal function deterioration was found in 8 (15.3%) ureters and was less common
      in those with successful surgeries than in those with failures (9.5% vs. 40.0%; P
      = 0.035). No significant predictive factor for renal function deterioration or
      urinary tract infection was found. Conclusion: Successful short-term outcomes of
      ES are expected in low-grade vesicoureteral reflux, especially when a mound is
      detected by postoperative ultrasonography. However, unpredictable long-term renal
      deterioration warrants continued follow-up.

PMID- 30224909
TI  - Effect of Ambient Light Exposure on Ocular Fatigue during Sleep.
AB  - Background: To investigate the influence of nocturnal ambient light on visual
      function and ocular fatigue. Methods: Sixty healthy subjects (30 men and 30
      women) aged 19 through 29 years with no history of ocular disease were recruited.
      All subjects spent 3 consecutive nights in the sleep laboratory. During the first
      and second nights, the subjects were not exposed to light during sleep, but
      during the third night, they were exposed to ambient light, measuring 5 or 10 lux
      at the eye level, which was randomly allocated with 30 subjects each. The visual
      function and ocular fatigue were assessed at 7 a.m. on the 3rd and 4th mornings,
      using best-corrected visual acuity, refractive error, conjunctival hyperemia,
      tear break-up time, maximal blinking interval, ocular surface temperature, and
      subjective symptoms reported on a questionnaire. Results: Three men and three
      women subjects failed to complete the study (4 in the 5 lux; 2 from the 10 lux).
      For the entire 54 subjects, tear break-up time and maximal blinking interval
      decreased (P = 0.015; 0.010, respectively), and nasal and temporal conjunctival
      hyperemia increased significantly after sleep under any ambient light (P < 0.001;
      0.021, respectively). Eye tiredness and soreness also increased (P = 0.004;
      0.024, respectively). After sleep under 5 lux light, only nasal conjunctival
      hyperemia increased significantly (P = 0.008). After sleep under 10 lux light,
      nasal and temporal conjunctival hyperemia, eye tiredness, soreness, difficulty in
      focusing, and ocular discomfort increased significantly (P < 0.05). Conclusion:
      Nocturnal ambient light exposure increases ocular fatigue. Avoiding ambient light
      during sleep could be recommended to prevent ocular fatigue.

PMID- 30224910
TI  - Corrigendum: Alexithymia and Autism Spectrum Disorder: A Complex Relationship.
AB  - [This corrects the article DOI: 10.3389/fpsyg.2018.01196.].

PMID- 30224911
TI  - Corrigendum: Clinical Characteristics and Predictors of Outcome for Onconeural
      Antibody-Associated Disorders: A Retrospective Analysis.
AB  - [This corrects the article DOI: 10.3389/fneur.2017.00584.].

PMID- 30224912
TI  - Corrigendum: An In vitro Study of Bio-Control and Plant Growth Promotion
      Potential of Salicaceae Endophytes.
AB  - [This corrects the article DOI: 10.3389/fmicb.2017.00386.].

PMID- 30224913
TI  - Handwritten Bangla Character Recognition Using the State-of-the-Art Deep
      Convolutional Neural Networks.
AB  - In spite of advances in object recognition technology, handwritten Bangla
      character recognition (HBCR) remains largely unsolved due to the presence of many
      ambiguous handwritten characters and excessively cursive Bangla handwritings.
      Even many advanced existing methods do not lead to satisfactory performance in
      practice that related to HBCR. In this paper, a set of the state-of-the-art deep
      convolutional neural networks (DCNNs) is discussed and their performance on the
      application of HBCR is systematically evaluated. The main advantage of DCNN
      approaches is that they can extract discriminative features from raw data and
      represent them with a high degree of invariance to object distortions. The
      experimental results show the superior performance of DCNN models compared with
      the other popular object recognition approaches, which implies DCNN can be a good
      candidate for building an automatic HBCR system for practical applications.

PMID- 30224914
TI  - Calculation and Analysis of Microstate Related to Variation in Executed and
      Imagined Movement of Force of Hand Clenching.
AB  - Objective: In order to investigate electroencephalogram (EEG) instantaneous
      activity states related to executed and imagined movement of force of hand
      clenching (grip force: 4 kg, 10 kg, and 16 kg), we utilized a microstate analysis
      in which the spatial topographic map of EEG behaves in a certain number of
      discrete and stable global brain states. Approach: Twenty subjects participated
      in EEG collection; the global field power of EEG and its local maximum were
      calculated and then clustered using cross validation and statistics; the 4
      parameters of each microstate (duration, occurrence, time coverage, and
      amplitude) were calculated from the clustering results and statistically analyzed
      by analysis of variance (ANOVA); finally, the relationship between the microstate
      and frequency band was analyzed. Main Results: The experimental results showed
      that all microstates related to executed and imagined grip force tasks were
      clustered into 3 microstate classes (A, B, and C); these microstates generally
      transitioned from A to B and then from B to C. With the increase of the target
      value of executed and imagined grip force, the duration and time coverage of
      microstate B gradually decreased, while these parameters of microstate C
      gradually increased. The occurrence times of microstate B and C related to
      executed grip force were significantly more than those related to imagined grip
      force; furthermore, the amplitudes of these 3 microstates related to executed
      grip force were significantly greater than those related to imagined grip force.
      The correlation coefficients between the microstates and the frequency bands
      indicated that the microstates were correlated to mu rhythm and beta frequency
      bands, which are consistent with event-related desynchronization/synchronization
      (ERD/ERS) phenomena of sensorimotor rhythm. Significance: It is expected that
      this microstate analysis may be used as a new method for observing EEG
      instantaneous activity patterns related to variation in executed and imagined
      grip force and also for extracting EEG features related to these tasks. This
      study may lay a foundation for the application of executed and imagined grip
      force training for rehabilitation of hand movement disorders in patients with
      stroke in the future.

PMID- 30224916
TI  - Thrombocytosis as a Marker for Postoperative Complications in Colorectal Surgery.
AB  - Background: Blood platelet measurement is a widely available and inexpensive test
      that is performed routinely. Platelets are thought to act by inducing
      inflammation and play a role in clotting and antimicrobial defence. A
      postoperative rise in the platelet count (thrombocytosis) is often dismissed as
      an incidental finding, but there is growing evidence to suggest that it may act
      as an indicator to underlying pathology. It correlates with significant pyogenic
      infections as well as multiple malignancies. In addition to this, recent research
      indicates that thrombocytosis may be a useful prognostic indicator for
      postoperative outcomes in patients with malignancies. In patients undergoing
      surgery for gastric cancer, a combination of platelet count and neutrophil-to
      lymphocyte (NLR) ratio collected preoperatively was shown to correlate with
      postoperative survival. Objective: To evaluate whether there is a positive
      correlation between pre- and postoperative thrombocytosis and the risk of
      complications following colorectal surgery. Methods: This was a retrospective
      observational study based in Morriston Hospital, Swansea. Patients undergoing
      elective colorectal surgery for an 18-month period between 2014 and 2016 were
      included. Data on patient demographics, pre- and postoperative platelet count,
      the first date at which the highest platelet count was recorded, length of stay,
      type of operation, and postoperative complications using the Clavien-Dindo
      classification was obtained from the theatre booking software (TOMS) and Welsh
      Clinical Portal. Pearson's chi-square test was used for the analysis of the
      categorical variables. Results: Of the 201 patients studied, 75 (37%) had
      postoperative thrombocytosis (platelets >= 500 * 109/L, range 501-1136), 120
      (59%) had postoperative normocytosis (platelets < 500 * 109/L, range 107-499),
      and 6 (2.9%) patients were excluded due to insufficient data. Peak platelet level
      was seen at a median of 8 days postoperatively but ranged from days 1 to 49. In
      patients with thrombocytosis, the mean time to peak platelet count was 9.5 days
      and ranged 1 to 49 days. 101/195 (52%) patients had a Clavien-Dindo III/V
      postoperative complication: 63% patients with postoperative normocytosis and 24%
      with postoperative thrombocytosis. In the thrombocytosis group, 16/75 (21%) were
      found to have postoperative pelvic collections compared to 1/120 (0.8%) of the
      normocytic patients. The total percentage of medical complications (44% versus
      20%, p = 0.006) and surgical complications (64% versus 15.8%, p = 0.0001) was
      higher in the thrombocytosis group compared to the normocytosis group.
      Conclusion: In this retrospective study, thrombocytosis was shown to have a
      positive correlation with postoperative medical and surgical complications. An
      elevated platelet count in the postoperative period should alert the clinician to
      a developing complication. We recommend that further studies with a larger sample
      size would test the specific associations with individual complications.

PMID- 30224915
TI  - Superior Mesenteric Artery Syndrome: Clinical, Endoscopic, and Radiological
      Findings.
AB  - Background: The superior mesenteric artery (SMA) syndrome is a rare entity
      presenting with upper gastrointestinal tract obstruction and weight loss. Studies
      to determine the optimal methods of diagnosis and treatment are required. Aims
      and Methods: This study aims at analyzing the clinical presentation, diagnosis,
      and management of SMA syndrome. Ten cases of SMA syndrome out of 2074
      esophagogastroduodenoscopies were suspected. A contrast-enhanced computed
      tomography (CECT) scan was performed to confirm the diagnosis. After, a
      gastroenterologist and a nutritionist personalized the therapy. Furthermore, we
      compared the demographical, clinical, endoscopic, and radiological parameters of
      these cases with a control group consisting of 10 cases out of 2380 EGDS of
      initially suspected (but not radiologically confirmed) SMA over a follow-up 2
      year period (2015-2016). Results: The prevalence of SMA syndrome was 0.005%.
      Median age and body mass index were 23.5 years and 21.5 kg/m2, respectively.
      Symptoms developed between 6 and 24 months. Median aortomesenteric angle and
      aorta-SMA distance were 22 and 6 mm, respectively. All patients improved on
      conservative treatment. In our series, a marked (>5 kg) weight loss (p = 0.006)
      and a long-standing presentation (more than six months in 80% of patients) (p =
      0.002) are significantly related to a diagnosis of confirmed SMA syndrome at CECT
      after an endoscopic suspicion. A "resembling postprandial distress syndrome
      dyspepsia" presentation may be helpful to the endoscopist in suspecting a latent
      SMA syndrome (p = 0.02). The narrowing of both the aortomesenteric angle (p =
      0.001) and the aortomesenteric distance (p < 0.001) was significantly associated
      with the diagnosis of SMA after an endoscopic suspicion; however, the narrowing
      of the aortomesenteric distance seemed to be more accurate, rather than the
      narrowing of the aortomesenteric angle. Conclusion: SMA syndrome represents a
      diagnostic and therapeutic challenge. Our results show the following findings:
      the importance of the endoscopic suspicion of SMA syndrome; the preponderance of
      a long-standing and chronic onset; a female preponderance; the importance of the
      nutritional counseling for the treatment; no need of surgical intervention; and
      better diagnostic accuracy of the narrowing of the aorta-SMA distance. Larger
      prospective studies are needed to clarify the best diagnosis and management of
      the SMA syndrome.

PMID- 30224917
TI  - Physical Activity Scale for the Elderly: Translation, Cultural Adaptation, and
      Validation of the Italian Version.
AB  - Objective: The aim of the study was to translate and culturally adapt the
      Physical Activity Scale for the Elderly into Italian (PASE-I) and to evaluate its
      psychometric properties in the Italian older adults healthy population. Methods:
      For translation and cultural adaptation, the "Translation and Cultural Adaptation
      of Patient-Reported Outcomes Measures" guidelines have been followed.
      Participants included healthy individuals between 55 and 75 years old. The
      reliability and validity were assessed following the "Consensus-Based Standards
      for the Selection of Health Status Measurement Instruments" checklist. To
      evaluate internal consistency and test-retest reliability, Cronbach's alpha and
      Intraclass Correlation Coefficient (ICC) were, respectively, calculated. The Berg
      Balance Score (BBS) and the PASE-I were administered together, and Pearson's
      correlation coefficient was calculated for validity. Results: All the PASE-I
      items were identical or similar to the original version. The scale was
      administered twice within a week to 94 Italian healthy older people. The mean
      PASE-I score in this study was 159+/-77.88. Cronbach's alpha was 0.815 (p < 0.01)
      and ICC was 0.977 (p < 0.01). The correlation with the BBS was 0.817 (p < 0.01).
      Conclusions: The PASE-I showed positive results for reliability and validity.
      This scale will be of great use to clinicians and researchers in evaluating and
      managing physical activities in the Italian older adults population.

PMID- 30224918
TI  - Interplay between Body Size Measures and Thyroid Cancer Aggressiveness: A
      Retrospective Analysis.
AB  - Considering controversial data about the relationship between body size and
      prognosis of differentiated thyroid cancer (DTC), the current study aimed to
      assess the influence of body weight, body mass index (BMI), and body surface area
      (BSA) on DTC. We conducted a retrospective analysis of patients' records from the
      Thyroid Cancer Unit, assessing body size measures, clinical and laboratory
      prognostic factors, and disease evolution. 337 patients, aged 45.95 +/- 13.04
      years old, with BMI of 27.87 +/- 5.13 kg/m2 and BSA of 1.74 +/- 0.18 m2 were
      enrolled. After 9.5 +/- 6.9 years of follow-up, 87.29% of patients were disease
      free and 12.71% had persistent disease; no patient had deceased. Patients aged
      <45 years old with extrathyroidal invasion tumor had greater baseline body weight
      and BSA than those without extrathyroidal invasion (median 79.5 kg versus 67 kg
      and 1.85 m2 versus 1.74 m2). Women with poorly differentiated tumor and patients
      aged >=45 years old with distant metastasis presented greater weight loss during
      follow-up compared to patients without such characteristics (median -2 kg versus
      +1.5 kg and -3 kg versus +1 kg, respectively). The relationship between body size
      and DTC evolution was not observed. In conclusion, higher weight and BSA were
      associated with a greater chance of extrathyroidal tumor invasion in younger
      patients. Specific subgroups of patients with aggressive disease presented higher
      weight loss. Young patients with higher BSA should be carefully treated due to
      possible worse prognosis related to increased incidence of extrathyroid invasion.
      Findings related to tumor aggressiveness and weight loss in specific groups
      deserve further mechanistic studies.

PMID- 30224919
TI  - Cardiovascular Risk and Metabolic Syndrome Characteristics in Patients with
      Nonfunctional Pituitary Macroadenoma.
AB  - Context: An elevated incidence of type 2 diabetes and cardiovascular disease
      (CVD) has been reported in patients with nonfunctional pituitary macroadenoma
      (NFPMA). There is no information about metabolic syndrome and cardiovascular risk
      in patients with NFPMA in our population. Objective: Analyze the metabolic
      syndrome (MetS) components and estimate cardiovascular risk in patients with
      NFPMA. Design and Setting: Retrospective study, at the tertiary care center.
      Patients and Methods: 71 patients with NFPMA treated according to a
      preestablished multimodal protocol. Main Outcome Measures: Prevalence of
      diabetes, hypertension, high cholesterol, obesity, and cardiovascular risk and
      its relationship with the clinical and biochemical characteristics. Results: The
      prevalence of diabetes, hypertension, high cholesterol, and obesity at diagnosis
      was 30%, 27%, 48%, and 85% and did not change upon the last visit. The prevalence
      of MetS changes from 54 to 48% (p = 0.001). NFPMA patients showed a significant
      increase risk for high total cholesterol (SMR 1.68, 95% CI 1.28-2.17, p = 0.001)
      and diabetes (SMR 3.19, 95% CI 2.19-4.49, p = 0.01). According to Globorisk, the
      male gender was an evidence of high CVD before (81% versus 18%, p = 0.01) and
      after (72% versus 28%, p = 0.01) multimodal treatment. Conclusion: A high
      prevalence of cardiovascular and metabolic disease and a high cardiovascular risk
      were evidenced in patients with NFPMA, especially in men. Risk factors such as
      the personal history of hypertension and dyslipidemia could explain the
      foregoing, so the control and treatment of metabolic parameters and
      cardiovascular risk should be an integral part of the follow-up of these
      patients.

PMID- 30224920
TI  - Willingness to Work and the Working Environment of Japanese Dental Hygienists.
AB  - Japanese dental hygienists' employment rate is low. The environment factors and
      daily job contents that contribute to willingness to work of Japanese dental
      hygienists and their structures were investigated. A cross-sectional survey was
      conducted using a self-administered postal questionnaire distributed for one
      thousand and twenty-three members of Japan Dental Hygienist Association
      registered in Iwate prefecture affiliation. Three items concerning willingness to
      work, satisfaction for the 9 items about working environment, anxiety for work,
      and 106 daily job contents were used for analysis. Structural equation modeling,
      decision analysis, and correspondence analysis were carried out. The present
      study found that working environment such as interpersonal relationship was more
      important than social environment such as salary for the regular employee of
      Japanese dental hygienist working at private dental office. However, salary was
      only the determinant for the dental hygienist who strongly disliked their work.
      And daily job contents affected the willingness to work. Especially, jobs
      concerned with prosthodontic treatments were of major concern. Improving the
      working environment and avoiding assignment of tasks that require lower level of
      skill may improve dental hygienists' willingness to work and may assist to
      improve the employment rate of dental hygienist in Japan.

PMID- 30224921
TI  - Detection, Characterization, and Clinical Application of Mesenchymal Stem Cells
      in Periodontal Ligament Tissue.
AB  - Mesenchymal stem cells (MSCs) are a kind of somatic stem cells that exert a
      potential to differentiate into multiple cell types and undergo robust clonal
      self-renewal; therefore, they are considered as a highly promising stem cell
      population for tissue engineering. MSCs are identified in various adult organs
      including dental tissues. Periodontal ligament (PDL) is a highly specialized
      connective tissue that surrounds the tooth root. PDL also contains MSC
      population, and many researchers have isolated them and performed their detailed
      characterization. Here, we review the current understanding of the features and
      functions of MSC population in PDL tissues and discuss their possibility for the
      application of PDL regeneration.

PMID- 30224922
TI  - Current Strategies to Generate Human Mesenchymal Stem Cells In Vitro.
AB  - Mesenchymal stem cells (MSCs) are heterogeneous multipotent stem cells that are
      involved in the development of mesenchyme-derived evolving structures and organs
      during ontogeny. In the adult organism, reservoirs of MSCs can be found in almost
      all tissues where MSCs contribute to the maintenance of organ integrity. The use
      of these different MSCs for cell-based therapies has been extensively studied
      over the past years, which highlights the use of MSCs as a promising option for
      the treatment of various diseases including autoimmune and cardiovascular
      disorders. However, the proportion of MSCs contained in primary isolates of adult
      tissue biopsies is rather low and, thus, vigorous ex vivo expansion is needed
      especially for therapies that may require extensive and repetitive cell
      substitution. Therefore, more easily and accessible sources of MSCs are needed.
      This review summarizes the current knowledge of the different strategies to
      generate human MSCs in vitro as an alternative method for their applications in
      regenerative therapy.

PMID- 30224923
TI  - Potential Effect of Exosomes Derived from Cancer Stem Cells and MSCs on
      Progression of DEN-Induced HCC in Rats.
AB  - Cross talk, mediated by exosomes, between normal stem cells and cancer stem cells
      (CSCs) in the tumor microenvironment has been given less attention so far. In
      addition, no publications are available in the literature that address the in
      vivo impact of exosomes derived from CSCs and mesenchymal stem cells (MSCs) on
      progression of long-term hepatocellular carcinoma (HCC). Herein, we hypothesized
      that transfer of exosomes among the cells in the HCC microenvironment could
      either induce or inhibit tumor growth and metastasis depending on their source.
      To check this hypothesis, we investigated the effect of exosomes coming from two
      different stem cell populations, hepatic CSCs and bone marrow (BM) MSCs, on
      progression of long-term DEN-induced HCC in rats and the involved underlying
      mechanisms. CSCs-exosomes induced a significant increase in liver relative weight
      and serum levels of cancer markers (AFP and GGT) and liver enzymes (ALT, AST, and
      ALP), intensive immunostaining for the HCC marker GST-P, and an increased number
      and area of tumor nodules as compared to HCC rats injected by PBS. CSCs-exosomes
      also decreased apoptosis (marked by downregulation of Bax and p53 and
      upregulation of Bcl2, and increased immunostaining of PCNA), increased
      angiogenetic activity (revealed by upregulation of VEGF), enhanced metastasis and
      invasiveness (indicated by upregulation of P13K and ERK proteins and their
      downstream target MMP9 and downregulation of TIMP1), and induced epithelial
      mesenchymal transition (marked by increased serum and hepatic level of TGFbeta1
      mRNA and protein). Notably, CSCs-exosomes also elevated HCC exosomal microRNA
      (miR) 21, exosomal long noncoding (lnc) RNA Tuc339, lncHEIH, and the HCC
      lncHOTAIR and decreased liver miR122 and HCC miRs (miR148a, miR16, and miR125b).
      All these cellular, functional, and molecular changes were reversed following
      injection of BM-MSCs-exosomes. However, both CSCs- and MSCs-exosomes failed to
      change the elevated oxidative stress or the inhibited antioxidant activities
      induced by HCC. Collectively, our results revealed a tumor stimulatory effect
      (induction of tumor growth, progression, and metastasis) for exosomes derived
      from CSCs and an inhibitory effect for exosomes derived from MSCs. These results
      provide valuable insight on the effect of CSCs- and MSCs-exosomes on HCC growth
      and progression in vivo, which may be helpful to understand the mechanism of HCC
      development.

PMID- 30224924
TI  - Water, Sanitation, and Hygiene Service Availability at Rural Health Care
      Facilities in Southwestern Uganda.
AB  - There is a paucity of information on the state of water, sanitation, and hygiene
      (WASH) at health care facilities in Uganda. A survey on WASH service availability
      was conducted at 50 health care facilities across 4 districts of rural
      southwestern Uganda between September and November 2015. The main water points at
      the majority (94%) of the health care facilities were improved sources, while
      improved toilets were available at 96% of the health care facilities visited.
      Hospitals had the poorest toilet to patient ratio (1 : 63). Only 38% of the
      health care facilities had hand washing facilities at the toilets. The lack of
      hand washing facilities was most prominent at the level IV health centre toilets
      (71%). Hand washing facilities were available at other points within most (76%)
      of the health care facilities. However, both water and soap were present at only
      24% of these health care facilities. The poor toilet to patient/caregiver ratios
      particularly in the high volume health care facilities calls for the provision of
      cheaper options for improved sanitation in these settings. Priority should also
      be given to the sustainable provision of hygiene amenities such as soap for hand
      washing particularly the high patient volume health care facilities, in this case
      the level IV health centres and hospitals.

PMID- 30224925
TI  - SYKT Alleviates Doxorubicin-Induced Cardiotoxicity via Modulating ROS-Mediated
      p53 and MAPK Signal Pathways.
AB  - Backgrounds. Doxorubicin (DOX) is an effective therapeutic drug for malignant
      tumors; however, its clinical applications were limited by its side effects,
      especially the cardiotoxicity caused by ROS-mediated p53 and MAPK signal
      pathways' activation-induced cell apoptosis. Sanyang Xuedai mixture (SYKT) has
      been reported as an antioxidant agent and attenuated DOX-induced cardiotoxicity
      by targeting ROS-mediated apoptosis, but the mechanisms are still not fully
      delineated. Objective. This study aimed at investigating whether SYKT alleviated
      DOX-induced cardiotoxicity by inhibiting ROS-mediated apoptosis and elucidating
      the role of ROS-mediated p53 and MAPK signal pathways' activation in this
      process. Materials and Methods. Identification, separation, and culture of mouse
      primary cardiomyocytes. Cells were treated with DOX (1 MUM), SYKT (30 mg/mL), or
      SYKT coupled with DOX. The p53 inhibitor Pifithrin-alpha (PFT-alpha), p38/MAPK
      inhibitor SB203583 (SB), and JNK inhibitor SP600125 (SP) were used as positive
      control. Western blot was employed to detected p53 and p38 as well as JNK
      expressions and the activation and translocation of Bax and cytochrome C. Flow
      cytometer (FCM) was used to detect the mitochondrial membrane potential and cell
      apoptosis. Results. After separation and culture, 95% of cells showed positive
      cTnI expression, which indicated that mouse primary cardiomyocytes were
      successfully identified in our research. DOX activated p53 and MAPK signal
      pathways in a time-dependent manner, which were inactivated by being cotreated
      with SYKT, PFT-alpha, or SB, respectively. DOX significantly decreased Bax and
      increased cytochrome c expressions in the cytoplasm, whereas Bax was upregulated
      and cytochrome c was downregulated in the mitochondria, which were reversed by
      SYKT treatment. Besides, DOX reduced mitochondria membrane potential (MMP) in
      cardiomyocytes compared to the control group; SYKT recovered its MMP and
      attenuated DOX-induced cardiomyocyte injury. Of note, DOX increased the
      expression levels of cleaved caspase-3 as well as poly ADP-ribose polymerase
      (PARP) and promoted cell apoptosis, which were also reversed by SYKT treatment.
      Discussion and Conclusions. Our results indicated that SYKT alleviated DOX
      induced cardiotoxicity by inhibiting p53 and MAPK signal pathways' activation
      mediated apoptosis, and it might serve as a potential therapeutic agent for DOX
      induced cardiotoxicity.

PMID- 30224926
TI  - Clinical Evaluation of Herbal Medicine (ICH-012) in Treating Acute Cerebral
      Haemorrhage: Safety and Efficacy from 6- to 72-Hour Time Window (CRRICHTrial-II).
AB  - Background: Hypertensive intracerebral haemorrhage (HICH), which is characterized
      by rapid change, high morbidity, and mortality, is extremely dangerous. Both
      medical and surgical treatments lack definitive evidence and remain
      controversial. A prospective RCT that we have conducted has shown that the usage
      of the herbal medicine ICH-012 within 6 h of the event may increase the risk of
      haematoma enlargement and gastrointestinal bleeding. However, the volume of
      haematoma remains stable after 6 h. Thus, we will increase the time window to the
      period from 6 to 72 h after onset to evaluate the safety and efficacy of ICH-012
      treating ICH (ClinicalTrial.gov ID: NCT03354026). Methods/Design: The CRRICHTrial
      II study, a prospective, double-blinded, controlled, multicentre RCT, includes
      three groups: A, B, and C. Group A patients were treated with 8 herbal medicines
      (with 2 herbal medicines of Hirudo and Tabanus as well as 6 other combined herbal
      medicines of Group B) and Group C were placebo. Patients should meet all the
      inclusion criteria: age between 18 and 80 and diagnosis of HICH by brain CT scan
      between 6 and 72 h from the onset. The CT scan will be taken at four critical
      time points: baseline, between 6 and 72h, 24h after onset, and between 10 and 14
      days after onset. The drug intervention lasts 10 days, and there is a follow-up
      visit taken after 90 days. The haematoma enlargement after 24 h onset as
      demonstrated by CT is the primary outcome. Discussion: A large amount of data
      from high-quality RCTs is needed for the extensive clinical application of herbal
      medicine. The CRRICHTrial-II will evaluate the safety and effectiveness of ICH
      012 in a safer time window between 6 and 72 h and investigate the possible
      mechanisms of action and direction of herbal medicine in the haematoma growth
      after HICH. Trial registration at ClinicalTrial.gov, ID: NCT03354026, is
      registered on 23rd Nov. 2017.

PMID- 30224927
TI  - Bushen-Yizhi Formula Alleviates Neuroinflammation via Inhibiting NLRP3
      Inflammasome Activation in a Mouse Model of Parkinson's Disease.
AB  - Parkinson's disease (PD), the second most common neurodegenerative disease, is
      characterized by the progressive loss of dopaminergic neurons in the substantia
      nigra. Although the molecular mechanisms underlying dopaminergic neuronal
      degeneration in PD remain unclear, neuroinflammation is considered as the vital
      mediator in the pathogenesis and progression of PD. Bushen-Yizhi Formula (BSYZ),
      a traditional Chinese medicine, has been demonstrated to exert
      antineuroinflammation in our previous studies. However, it remains unclear
      whether BSYZ is effective for PD. Here, we sought to assess the neuroprotective
      effects and explore the underlying mechanisms of BSYZ in a 1-methyl-4-phenyl-1,
      2, 3, 6-tetrahydropyridine- (MPTP-) induced mouse model of PD. Our results
      indicate that BSYZ significantly alleviates the motor impairments and
      dopaminergic neuron degeneration of MPTP-treated mice. Furthermore, BSYZ
      remarkably attenuates microglia activation, inhibits NLPR3 activation, and
      decreases the levels of inflammatory cytokines in MPTP-induced mouse brain. Also,
      BSYZ inhibits NLRP3 activation and interleukin-1beta production of the 1-methyl-4
      phenyl-pyridinium (MPP+) stimulated BV-2 microglia cells. Taken together, our
      results indicate that BSYZ alleviates MPTP-induced neuroinflammation probably via
      inhibiting NLRP3 inflammasome activation in microglia. Collectively, BSYZ may be
      a potential therapeutic agent for PD and the related neurodegeneration diseases.

PMID- 30224928
TI  - Adjuvant Therapy Using Mistletoe Containing Drugs Boosts the T-Cell-Mediated
      Killing of Glioma Cells and Prolongs the Survival of Glioma Bearing Mice.
AB  - Viscum album L. extracts (VE) are applied as complementary cancer therapeutics
      for more than one century. Extracts contain several compounds like mistletoe
      lectins (ML) 1-3 and viscotoxins, but also several minor ingredients. Since ML-1
      has been described as one of the main active components harboring antitumor
      activity, purified native or recombinant ML-1 has been also used in clinical
      trials in the last years. The present study examined and compared the
      immunoboosting effects of three ML-1 containing drugs (the extract ISCADOR Qu,
      the recombinant ML-1 Aviscumine, and purified native ML-1) in the context of the
      T-cell mediated killing of glioma cells. Additionally we examined the possible
      underlying T-cell stimulating mechanisms. Using cocultures of immune and glioma
      cells, a PCR-based microarray, quantitative RT-PCR, and an antibody-based array
      to measure cytokines in blood serum, immunosupporting effects were determined. A
      highly aggressive, orthotopic, immunocompetent syngeneic mouse glioma model was
      used to determine the survival of mice treated with ISCADOR Qu alone or in
      combination with tumor irradiation and temozolomide (TMZ). Treatment of
      glioblastoma (GBM) cells with ISCADOR Qu that contains a high ML concentration,
      but also viscotoxins and other compounds, as well as with Aviscumine or native ML
      1, enhanced the expansion of cancer cell-specific T-cells as well as T-cell
      mediated tumor cell lysis, but to a different degree. In GBM cells all three ML-1
      containing preparations modulated the expression of immune response associated
      genes. In vivo, subcutaneous ISCADOR Qu injections at increasing concentration
      induced cytokine release in immunocompetent VM/Dk-mice. Finally, ISCADOR Qu, if
      applied in combination with tumor irradiation and TMZ, further prolonged the
      survival of glioma mice. Our findings indicate that ML-1 containing drugs enhance
      anti-GBM immune responses and work in synergy with radiochemotherapy. Therefore,
      adjuvant mistletoe therapy should be considered as an auspicious treatment option
      for glioma patients.

PMID- 30224929
TI  - Difference between Right and Left Facial Surface Electromyography in Healthy
      People.
AB  - Introduction: The study was to see whether there were differences in values of
      facial surface electromyography in subjects of good heath by muscles, age, and
      sex. Methods: It draws ratio between lower value and higher value (R-LV/HV) and
      asymmetry index (AI), based on root mean square (RMS) from measurement of facial
      surface electromyography (sEMG) in 154 people of healthy people (male:female =
      70:84) aging between more than 20 and less than 70. Results: For R-LV/HV, it
      averages 81.70+/-14.60% on frontalis muscle, 73.74+/-19.12% on zygomaticus
      muscle, and 79.72+/-14.77% on orbicularis oris muscle. With analysis of the AI
      average was 10.87+/-10.14% on frontalis muscle, 16.71+/-14.79% on zygomaticus
      muscle, and 12.10+/-10.05% on orbicularis oris muscle. Both values were
      statistically significant in three parts of muscles as shown. Both of R-LV/HV and
      AI show no statistically significant difference on age and sex (p>0.05).
      Conclusions: It could provide basic data for the future diagnosis of facial nerve
      palsy patients by measuring facial sEMG values for healthy people.

PMID- 30224930
TI  - Safety and Efficacy of Ferula asafoetida in Functional Dyspepsia: A Randomized,
      Double-Blinded, Placebo-Controlled Study.
AB  - Despite the availability of various synthetic drugs for the treatment of
      functional dyspepsia (FD), the side effects and their cost have always created a
      great interest in the search for novel natural alternatives for the management of
      gut disorders. The present contribution reports the safety and efficacy of the
      kitchen spice asafoetida (Ferula asafoetida) in FD for the first time. In the
      double-blinded, placebo-controlled study, 43 subjects diagnosed to have moderate
      to severe discomforts of nonulcer FD were randomized to receive hard-shell
      capsules (250 mg * 2/day) of either placebo (n=22) or a food-grade formulation of
      asafoetida (Asafin) (n=21) for 30 days. When evaluated by a set of validated
      indexing tools (GSRS, GDSS, and NDI), almost 81% in the Asafin group showed
      significant (p < 0.01) improvement in the overall score and quality of life as
      compared to the placebo. At the end of the study, 66% of subjects in the Asafin
      group remained symptoms-free. Although the symptoms score improved significantly
      in both the groups (from -5.67 to -25.29 in Asafin group versus -1.55 to -6.0 in
      the placebo; p <= 0.001), the relative percentage of subjects in the Asafin group
      with more than 80% reduction in various symptoms were: bloating (58%), appetite
      (69%), postprandial fullness (74%) motion sickness (75%), and digestion (77%) as
      compared to less than 10% nonspecific improvement in the placebo group. All the
      subjects remained safe with no adverse events or variations in haematological and
      biochemical parameters. The study was registered at http://ctri.nic.in/
      (CTRI/2018/ 01/011149).

PMID- 30224932
TI  - "Diabetes and Metabolism Disorders Medicinal Plants: A Glance at the Past and a
      Look to the Future 2018": Antihyperglycemic Activity of Hamelia patens Jacq.
      Extracts.
AB  - Diabetes is one the world's most widespread diseases, affecting over 327 million
      people and causing about 300,000 deaths annually. Despite great advances in
      prevention and therapy, existing treatments for this disorder have serious side
      effects. Plants used in traditional medicine represent a valuable source in the
      search for new medicinal compounds. Hamelia patens Jacq. has been used for
      treating diabetes and, so far, no reports have been made on the in vivo
      antihyperglycemic activity of this plant. The present study on H. patens aimed to
      test the antihyperglycemic effect of repeated administrations of the crude and
      fractional methanolic extracts (CME and FME, respectively) on rats with
      hyperglycemia induced by streptozotocin. After 10 administrations (20 days), each
      extract had lowered blood glucose to a normal level. The extracts produced
      effects similar to metformin. Of the five compounds identified by chromatographic
      analysis of the extracts, epicatechin and chlorogenic acid demonstrated
      antihyperglycemic effect. The antioxidant activity of the extracts was evidenced
      by their IC50 values (51.7 and 50.7 MUg/mL, respectively). The LD50>=2000 mg/Kg
      suggests low toxicity for both CME and FME. Thus, considering that the
      antihyperglycemic and antioxidant effects of metformin and extracts from H.
      patens were comparable, the latter may be efficacious for treating diabetes.

PMID- 30224931
TI  - Investigation of Lake Heviz Mineral Water Balneotherapy and Heviz Mud Treatment
      in Murine Osteoarthritis and Rheumatoid Arthritis Models.
AB  - Arthritic diseases are the most frequent causes of chronic pain and disability.
      Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial
      inflammation and progressive structural joint damage. Osteoarthritis is a
      degenerative process of the articular cartilage associated with hypertrophic
      changes in the bone. The aim of the present study was to investigate the anti
      inflammatory and analgesic effects of Heviz thermal water and mud in monosodium
      iodoacetate- (MIA-) (25 mg/ml, 20 MUl i.a.) induced osteoarthritis and Complete
      Freund's adjuvant- (CFA-) (1 mg/ml, 50-50 MUl s.c) induced rheumatoid arthritis
      murine models. The mechanonociceptive threshold of female NMRI mice (n=6- 8 mice/
      group) was measured by aesthesiometry, and paw volume was monitored with
      plethysmometry, knee joint diameter with digital micrometer, and dynamic weight
      bearing on the hind limbs with a Bioseb instrument. Periarticular bone
      destruction was assessed by SkyScan 1176 in vivo micro-CT. Inflammatory cytokines
      were detected by ELISA in plasma samples. Treatments (30 min, every working day)
      with tap water, sand, and a combined therapy of tap water and sand served as
      controls. Heviz medicinal water and combined treatment with water and mud
      significantly decreased the mechanical hyperalgesia and knee oedema in MIA
      induced osteoarthritis model. However, balneotherapy did not influence mechanical
      hyperalgesia, weight bearing, or oedema formation induced by CFA. Neither
      medicinal water nor mud treatment ameliorated deep structural damage of the bones
      or the joints in the animal models. On the basis of the present findings, we
      conclude that balneotherapy is an effective complementary treatment to reduce the
      pain sensation and swelling in degenerative joint diseases such as
      osteoarthritis. Our experimental data are in agreement with the previous human
      studies that also confirmed antinociceptive and anti-inflammatory effects of
      thermal water and Heviz mud treatments.

PMID- 30224933
TI  - Protective Effects of Liu Wei Di Huang Wan on the Liver, Orbitofrontal Cortex
      Nissl Bodies, and Neurites in MSG+PH-Induced Liver Regeneration Rat Model.
AB  - Introduction. To examine the protective effects of Liu Wei Di Huang Wan formula
      (LWDH) on liver and orbitofrontal cortex (OFC) injuries in monosodium glutamate
      (MSG) and partial hepatectomy (PH) rat model. Methods. Neonatal Wistar rats were
      given MSG or saline on postnatal days 2, 4, 6, 8, and 10. The rats were caged
      into five groups and treated accordingly at six weeks old as follows: Saline
      group, Saline+PH group, MSG group, MSG+PH group, and LWDH group (MSG+PH+LWDH).
      The PH was performed during week 8 by excision of the left and median hepatic
      lobes (occupying about 68% of whole liver).On day 8 after the PH, the rats were
      subjected to an inner OFT before being sacrificed. The liver and OFC were stained
      using H&E, ORO, or Nissl staining. The expression of neurotrophic factors (beta
      NGF, BDNF) was examined in the OFC lysates by ELISA. Serum levels of cytokines
      (IL-1beta, VEGF) were examined using the Bio-Plex suspension array. Results. LWDH
      increased the total distance traveled by the animals (p<0.05), and LWDH improved
      the integrity of the Nissl bodies in the OFC (mean area of the Nissl bodies,
      p<0.01; mean diameter, p<0.05; mean density, p<0.05; and IOD, p<0.01). There were
      less white area in the liver (p>0.05) and decreased hepatic steatosis (p<0.01) in
      LWDH group. LWDH administration decreased the expression of serum levels of IL
      1beta (p>0.05), while it increased VEGF (p>0.05) expression. LWDH administration
      increased the expression of BDNF (p>0.05) and beta-NGF (p>0.05) in the OFC, all
      as compared to the MSG+PH group. Conclusion. LWDH partly protected the animals
      from depressive-like behaviors in the MSG+PH-induced liver regeneration neonatal
      rat model. LWDH alleviated hepatic injury and steatosis and, furthermore,
      protected the Nissl body integrity and the growth of neurites.

PMID- 30224935
TI  - Skin Disease Recognition Method Based on Image Color and Texture Features.
AB  - Skin diseases have a serious impact on people's life and health. Current research
      proposes an efficient approach to identify singular type of skin diseases. It is
      necessary to develop automatic methods in order to increase the accuracy of
      diagnosis for multitype skin diseases. In this paper, three type skin diseases
      such as herpes, dermatitis, and psoriasis skin disease could be identified by a
      new recognition method. Initially, skin images were preprocessed to remove noise
      and irrelevant background by filtering and transformation. Then the method of
      grey-level co-occurrence matrix (GLCM) was introduced to segment images of skin
      disease. The texture and color features of different skin disease images could be
      obtained accurately. Finally, by using the support vector machine (SVM)
      classification method, three types of skin diseases were identified. The
      experimental results demonstrate the effectiveness and feasibility of the
      proposed method.

PMID- 30224934
TI  - Sirt1/Foxo Axis Plays a Crucial Role in the Mechanisms of Therapeutic Effects of
      Erzhi Pill in Ovariectomized Rats.
AB  - Background. Erzhi pill (EZP), a traditional Chinese herbal formula, has been
      widely used to treat postmenopausal osteoporosis (PMOP) in China. However, its
      molecular mechanisms remain unclear. The aim of the present study is to
      investigate the antiosteoporotic effect of EZP on an ovariectomized rat model of
      PMOP. We performed the biomarkers of bone metabolism disorder, bone morphology,
      bone mineral density (BMD), and bone biomechanics to confirm the successful
      establishment of the PMOP model. We then investigated the expression of
      biomarkers related to the Sirt1/Foxo axis. We also examined microRNA-132 (miR
      132), a regulator in the Sirtuin1 (Sirt1) expression. The bone metabolism
      disorder, bone morphology, BMD, and bone biomechanics in ovariectomized rats were
      improved by EZP administration. The antiosteoporotic effect of EZP was confirmed.
      We also found that the expressions of Sirt1, Runx2, Foxo1, and Foxo3a were
      downregulated in ovariectomized rats, while being then upregulated by EZP
      administration. And the expression of PPAR-gamma and miR-132 was upregulated in
      ovariectomized rats and then downregulated by EZP administration. These results
      provided evidence that Sirt1/Foxo axis related mechanism may play a crucial role
      in the therapeutic effects of EZP, indicating that Sirt1/Foxo axis can be
      considered as a potential therapeutic target for PMOP in the future.

PMID- 30224936
TI  - Genomic Subtypes of GISTs for Stratifying Patient Response to Sunitinib following
      Imatinib Resistance: A Pooled Analysis and Systematic Review.
AB  - Objectives: Sunitinib (a second-line chemotherapeutic agent that inhibits
      multiple kinases, including KIT and PDGFR) is widely used in imatinib-resistant
      patients with gastrointestinal stromal tumors (GISTs). However, diverse responses
      to sunitinib have been observed in the clinic. We aimed to evaluate whether the
      different GIST genotypes could be used to stratify patient response to sunitinib.
      Methods: We searched the PubMed, Embase, and Cochrane databases and included
      English-language literature published up to August 31, 2017. Inclusion criteria
      were GIST patients with KIT exon 9, KIT exon 11, or PDGFRA mutations and those
      without KIT/PDGFRA mutations (termed the wild-type genotype) who were receiving
      sunitinib within a clinical trial, and the efficacy evaluation was clinical
      benefit rate (CBR), median progression-free survival (PFS), and overall survival
      (OS). Odds ratios (ORs) for CBR and hazard ratios (HRs) for PFS and OS with 95%
      confidence intervals (CIs) in sunitinib-treated GIST patients with different
      genotypes were compared. Results: Seven studies totaling 531 patients were
      included. Patients with KIT mutations showed an improved CBR to sunitinib
      compared to those with PDGFRA mutations. In particular, those with the KIT exon 9
      or 11 mutation showed improved CBR over those with PDGFRA mutation. Moreover,
      GIST patients with the KIT exon 9 mutation showed improved CBR over those with
      the KIT exon 11 mutation. Patients without KIT/PDGFRA mutations (wild-type
      genotype) showed better CBR than those with PDGFRA mutations. Conclusion: GIST
      genotypes may be useful for stratifying patient response to sunitinib after
      imatinib resistance.

PMID- 30224937
TI  - A Novel Technique of Spectral Discrimination of Variants of Sickle Cell Anemia.
AB  - Sickle cell anemia (SCA) is an inherited blood disorder with worldwide incidence
      of 15%; out of this, it is found in up to 20% in countries like Kingdom of Saudi
      Arabia and Bahrain. The standard conventional method of detection is complete
      blood count (CBC) followed by hemoglobin electrophoresis or high-performance
      liquid chromatography (HPLC) or both. In this context, spectral detection of
      variants of sickle cell anemia (SCA) is an innovative technique, which when made
      accurate and reliable could be an effective alternative, since the
      instrumentation is compact (5 kg) and hence portable. This makes mass screening
      even in remote villages possible. In this paper, we give the essential aspects of
      fluorescent spectral features of sickle cell trait (SCT), sickle cell disease
      (SCD), beta (beta) thalassemia trait (BTT) + SCD, and beta (beta) thalassemia
      disease (BTD) + SCD. All the above four major variants could be discriminated
      among themselves and also from the normal control blood sample. All these
      analyses could be carried out with 5 ml of blood, in a time period of 10 minutes.
      The results of this paper give strong support for an alternative method, a
      spectral technique, for molecular-level diagnosis of sickle cell anemia and other
      closely related blood disorders.

PMID- 30224938
TI  - Visfatin Serum Levels Predict Mortality in Critically Ill Patients.
AB  - The adipokine visfatin, also termed pre-B-cell colony-enhancing factor (PBEF), is
      mainly derived from adipose tissue but has been implicated in the regulation of
      innate immune responses. We hypothesized that visfatin could be a potential
      circulating biomarker in critical illness and sepsis. We therefore measured serum
      levels of visfatin in a cohort of 229 critically ill medical patients upon
      admission to the intensive care unit (ICU). In comparison to 53 healthy controls,
      visfatin levels were significantly elevated in medical ICU patients, especially
      in patients with sepsis. Visfatin serum concentrations were strongly associated
      with disease severity and organ failure but did not differ between patients with
      or without obesity or type 2 diabetes. Visfatin levels correlated with biomarkers
      of renal failure, liver dysfunction, and other adipokines (e.g., resistin,
      leptin, and adiponectin) in critically ill patients. High visfatin levels at ICU
      admission indicated an increased mortality, both at the ICU and during long-term
      follow-up of approximately two years. Our data therefore demonstrate that
      circulating visfatin is a valuable biomarker for risk and prognosis assessment in
      critically ill patients. Furthermore, visfatin seems to be involved in the
      pathogenesis of excessive systemic inflammation, supporting further research on
      visfatin as a therapeutic target.

PMID- 30224939
TI  - Coagulation Factor Plasma Levels Following Administration of a 4-Factor
      Prothrombin Complex Concentrate for Rapid Vitamin K Antagonist Reversal in
      Japanese Patients.
AB  - Background: Four-factor prothrombin complex concentrates (4F-PCCs) have been
      approved for urgent vitamin K antagonist reversal in Western countries for many
      years. Ethnicity and genetic variations between populations may influence the
      pharmacokinetic profile of 4F-PCC treatments. Objective: To report plasma levels
      of vitamin K-dependent coagulation factors and proteins C and S in Japanese
      patients following administration of a 4F-PCC approved recently in Japan.
      Methods: This was a subanalysis of a prospective, open-label, Phase IIIb study in
      Japanese patients requiring rapid vitamin K antagonist reversal owing to major
      bleeding (n = 6) or need for urgent surgery (n = 5). International normalized
      ratio and plasma levels of factors II, VII, IX, and X, and proteins C and S were
      measured before PCC infusion and at specific time points for the next 24 hours.
      Adverse events and serious adverse events were recorded up to Day 14 and 45,
      respectively. Results: Rapid increases in plasma concentrations 30 minutes
      following 4F-PCC infusion were seen for all factors and proteins C and S, with
      median concentrations compared with baseline increasing by >=100% and 70% in the
      bleeding and surgical groups, respectively. A concurrent decrease in
      international normalized ratio was observed. Plasma levels for each factor and
      protein remained within physiologic levels throughout the assessment period. No
      relationship between thromboembolic events and elevated plasma levels was
      identified. Conclusions: Administration of 4F-PCC in Japanese patients receiving
      vitamin K antagonist anticoagulation therapy resulted in rapid and sustained
      increases in plasma levels and was well tolerated, indicating that this treatment
      is effective for the urgent reversal of vitamin K antagonist therapy in this
      population.

PMID- 30224940
TI  - Clinical Utility of Rapid Pathogen Identification for Detecting the Causative
      Organisms in Sepsis: A Single-Center Study in Korea.
AB  - Purpose: The aim of this pre- and postintervention cohort study was evaluating
      how effectively rapid pathogen identification with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) detected
      the causative organisms in sepsis. Methods: All consecutive adult patients who
      had bacteremia within 72 h of intensive care unit admission and met >=2 quick
      Sequential Organ Failure Assessment criteria at intensive care unit admission
      were analyzed. The patients whose microorganisms were identified via MALDI-TOF MS
      between March 2014 and February 2016 formed the postintervention group. The
      patients whose microorganisms were identified by using conventional methods
      between March 2011 and February 2013 formed the preintervention group. Results:
      The postintervention group (n=58) had a shorter mean time from blood draw to
      receiving the antimicrobial susceptibility results than the preintervention group
      (n=40) (90.2 +/- 32.1 vs. 108.7 +/- 43.1 h; p=0.02). The postintervention group
      was also more likely to have received active antimicrobial therapy by the time
      the susceptibility report became available (77% vs. 47%; p=0.005). Its 28-day
      mortality was also lower (40% vs. 70%; p=0.003). Univariate analysis showed that
      identification via MALDI-TOF MS (odds ratio, 0.28; 95% confidence interval, 0.12
      0.66; p=0.004) and active therapy (odds ratio, 0.38; 95% confidence interval,
      0.16-0.95; p=0.04) were associated with lower 28-day mortality. Conclusion: Rapid
      microorganism identification via MALDI-TOF MS followed by appropriate
      antimicrobial therapy may improve the clinical outcomes of patients with sepsis.

PMID- 30224941
TI  - Catheter-Associated Urinary Tract Infection and Obstinate Biofilm Producers.
AB  - Background: Biofilms, or colonies of uropathogen growing on the surface of
      indwelling medical devices, can inflict obstinate or recurring infection, thought
      provoking antimicrobial therapy. Methods: This prospective analysis included 105
      urine samples from catheterized patients receiving intensive care. Ensuing
      phenotypic identification, antibiotic sensitivity test was performed by modified
      Kirby-Bauer disc diffusion method following CLSI guidelines; MDR isolates were
      identified according to the combined guidelines of the European Centre for
      Disease Prevention and Control (ECDC) and the Centers for Disease Control and
      Prevention (CDC). Biofilm-forming uropathogens were detected by the tissue
      culture plate (TCA) method. Results: The predominant uropathogen in catheter
      associated UTIs (CAUTIs) was Escherichia coli 57%, followed by Klebsiella
      pneumonia 15%, Pseudomonas aeruginosa 12%, Staphylococcus aureus 8%, Enterobacter
      spp. 3%, Enterococcus faecalis, Acinetobacter spp., and Proteus mirabilis 1.5%,
      of which 46% isolates were biofilm producers. Prime biofilm producers were
      Escherichia coli 33%, followed by Klebsiella pneumoniae 30%, Pseudomonas
      aeruginosa 20%, Staphylococcus aureus 10%, Acinetobacter, and Enterobacter 3.33%.
      Multidrug resistance associated with biofilm producers were greater than biofilm
      nonproducers. The Gram-negative biofilm producers found 96.15%, 80.76%, 73.07%,
      53.84%, 53.84%, 46.15%, 19.23%, and 11.5% resistant to amoxyclave, ceftazidime,
      tetracycline, gentamicin, meropenem, nitrofurantoin, amikacin, imipenem, and
      fosfomycin, respectively. Gram-positive biofilm producers, however, were found
      100% resistant to tetracycline, cloxacillin, and amoxyclave: 66.67% resistant to
      ampicillin while 33.33% resistant to gentamicin, ciprofloxacin, and
      nitrofurantoin. Conclusion: High antimicrobial resistance was observed in biofilm
      producers than non-biofilm producers. Of recommended antimicrobial therapies for
      CAUTIs, ampicillin and amoxicillin-clavulanate were the least active antibiotics,
      whereas piperacillin/tazobactam and imipenem were found as the most effectual for
      gram-negative biofilm producer. Likewise, amoxicillin-clavulanate and
      tetracycline were the least active antibiotics, whereas vancomycin, fosfomycin,
      piperacillin-tazobactam, and meropenem were found as the most effective
      antibiotic for Gram-positive biofilm producer. In the limelight, the activity
      fosfomycin was commendable against both Gram-positive and Gram-negative biofilm
      producers.

PMID- 30224942
TI  - Sexual Risk, Behavior, and HIV Testing and Status among Male and Transgender
      Women Sex Workers and their Clients in Lima, Peru.
AB  - Objectives -: To determine the socio-demographics, sexual practices, and HIV
      prevalence of male sex workers (MSWs), transwomen sex workers (TSWs), and their
      male clients in Lima, Peru. Methods -: Following ethnographic mapping of sex work
      venues, we revisited randomly selected venues to survey MSWs, TSWs and their
      clients. Results -: MSWs and TSW clients are more educated than MSW clients and
      TSWs. Only 50% of TSW clients have received HIV testing. Self-reported HIV
      positivity is highest among MSW clients and TSWs. Conclusion -: Notable
      differences exist between MSWs and TSWs and their clients that can affect the
      health of these groups and warrant intervention.

PMID- 30224943
TI  - KERNEL-PENALIZED REGRESSION FOR ANALYSIS OF MICROBIOME DATA.
AB  - The analysis of human microbiome data is often based on dimension-reduced
      graphical displays and clusterings derived from vectors of microbial abundances
      in each sample. Common to these ordination methods is the use of biologically
      motivated definitions of similarity. Principal coordinate analysis, in
      particular, is often performed using ecologically defined distances, allowing
      analyses to incorporate context-dependent, non-Euclidean structure. In this
      paper, we go beyond dimension-reduced ordination methods and describe a framework
      of high-dimensional regression models that extends these distance-based methods.
      In particular, we use kernel-based methods to show how to incorporate a variety
      of extrinsic information, such as phylogeny, into penalized regression models
      that estimate taxonspecific associations with a phenotype or clinical outcome.
      Further, we show how this regression framework can be used to address the
      compositional nature of multivariate predictors comprised of relative abundances;
      that is, vectors whose entries sum to a constant. We illustrate this approach
      with several simulations using data from two recent studies on gut and vaginal
      microbiomes. We conclude with an application to our own data, where we also
      incorporate a significance test for the estimated coefficients that represent
      associations between microbial abundance and a percent fat.

PMID- 30224944
TI  - SS-31 Provides Neuroprotection by Reversing Mitochondrial Dysfunction after
      Traumatic Brain Injury.
AB  - SS-31, a novel mitochondria-targeted peptide, has been proven to provide
      neuroprotection in a variety of neurological diseases. Its role as a
      mitochondrial reactive oxygen species (ROS) scavenger and the underlying
      pathophysiological mechanisms in traumatic brain injury (TBI) are still not well
      understood. The aim of the designed study was to investigate the potential
      neuroprotective effects of SS-31 and fulfill our understanding of the process of
      the mitochondrial change in the modified Marmarou weight-drop model of TBI. Mice
      were randomly divided into sham, TBI, TBI + vehicle, and TBI + SS-31 groups in
      this study. Peptide SS-31 (5 mg/kg) or vehicle was intraperitoneally
      administrated 30 min after TBI with brain samples harvested 24 h later for
      further analysis. SS-31 treatment significantly reversed mitochondrial
      dysfunction and ameliorated secondary brain injury caused by TBI. SS-31 can
      directly decrease the ROS content, restore the activity of superoxide dismutase
      (SOD), and decrease the level of malondialdehyde (MDA) and the release of
      cytochrome c, thus attenuating neurological deficits, brain water content, DNA
      damage, and neural apoptosis. Moreover, SS-31 restored the expression of SIRT1
      and upregulated the nuclear translocation of PGC-1alpha, which were proved by
      Western blot and immunohistochemistry. Taken together, these data demonstrate
      that SS-31 improves the mitochondrial function and provides neuroprotection in
      mice after TBI potentially through enhanced mitochondrial rebiogenesis. The
      present study gives us an implication for further clinical research.

PMID- 30224945
TI  - miR-146a Attenuates Sepsis-Induced Myocardial Dysfunction by Suppressing IRAK1
      and TRAF6 via Targeting ErbB4 Expression.
AB  - Myocardial dysfunction is a major manifestation of sepsis and closely associated
      with the increased mortality. MicroRNA-146 is one of the most important microRNAs
      identified as a potent negative regulator in innate immune and inflammatory
      responses induced by lipopolysaccharide (LPS). We aimed to identify the role and
      potential regulatory mechanism of miR-146a in sepsis-induced cardiac dysfunction
      with the induction of ErbB4 signaling. H9C2 cells were treated with LPS to induce
      sepsis, and miR-146a overexpression significantly increased the cell viability,
      reduced the apoptosis and ROS level, and attenuated the release of
      proinflammatory cytokines including TNF-alpha and IL-1beta. Levels of ErbB4, p-NF
      kappaB, NF-kappaB, TRAF6, IRAK1, caspase 3, Bcl-2, and Bax were measured by
      Western blot. The overexpression of miR-146a significantly increased the ErbB4
      expression, decreased the expression of TRAF6, IRAK1, caspase 3, and the
      phosphorylation level of NF-kappaB, and also increased the Bcl-2/Bax ratio,
      suggesting the inhibition of inflammation and apoptosis. The protective effects
      were all abolished by the use of siErbB4. In conclusion, our results demonstrated
      that the overexpression of miR-146a mitigates myocardial injury by negatively
      regulating NF-kappaB activation and inflammatory cytokine production via
      targeting ErbB4 in LPS-induced sepsis.

PMID- 30224946
TI  - Chronic Exposure to Sodium Fluoride Triggers Oxidative Biochemistry Misbalance in
      Mice: Effects on Peripheral Blood Circulation.
AB  - The excessive fluoride (F) exposure is associated with damage to cellular
      processes of different tissue types, due to changes in enzymatic metabolism and
      breakdown of redox balance. However, few studies evaluate doses of F compatible
      with human consumption. Thus, this study evaluated the effects of chronic
      exposure to sodium fluoride (NaF) on peripheral blood of mice from the evaluation
      of biochemical parameters. The animals were divided into three groups (n = 10)
      and received three concentrations of NaF in the drinking water for 60 days: 0
      mg/L F, 10 mg/L F, and 50 mg/L F. The blood was then collected for trolox
      equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances
      (TBARS), concentrations of nitric oxide (NO), superoxide dismutase (SOD),
      catalase (CAT), and reduced glutathione (GSH). The results showed that doses of
      10 mg/L F and 50 mg/L F were able to increase TBARS concentration and decrease NO
      levels and CAT activity in the blood, but there was no statistical difference for
      SOD levels. The 50 mg/L F group showed an increase in TEAC levels and a decrease
      in the GSH content when compared to the control group. In this way, oxidative
      changes in blood from chronic exposure to F, especially at the highest dose,
      indicate that F may be a toxic agent and, therefore, the long-term exposure to
      excessive doses should be avoided.

PMID- 30026923
TI  - Real world evidence (RWE) - a disruptive innovation or the quiet evolution of
      medical evidence generation?
AB  - Stakeholders in healthcare are increasingly turning to real world evidence (RWE)
      to inform their decisions, alongside evidence from randomized controlled trials.
      RWE is generated by analysing data gathered from routine clinical practice, and
      can be used across the product lifecycle, providing insights into areas including
      disease epidemiology, treatment effectiveness and safety, and health economic
      value and impact. Recently, the US Food and Drug Administration and the European
      Medicines Agency have stated their ambition for greater use of RWE to support
      applications for new indications, and are now consulting with their stakeholders
      to formalize standards and expected methods for generating RWE. Pharmaceutical
      companies are responding to the increasing demands for RWE by developing
      standards and processes for each stage of the evidence generation pathway. Some
      conventions are already in place for assuring quality, whereas other processes
      are specific to the research question and data sources available. As evidence
      generation increasingly becomes a core role of medical affairs divisions in large
      pharmaceutical companies, standards of rigour will continue to evolve and
      improve. Senior pharmaceutical leaders can drive this change by making RWE a core
      element of their corporate strategy, providing top-level direction on how their
      respective companies should approach RWE for maximum quality. Here, we describe
      the current and future areas of RWE application within the pharmaceutical
      industry, necessary access to data to generate RWE, and the challenges in
      communicating RWE. Supporting and building on viewpoints from industry and
      publicly funded research, our perspective is that at each stage of RWE
      generation, quality will be critical to the impact that RWE has on healthcare
      decision-makers; not only where RWE is an established and evolving tool, but also
      in new areas that have the potential to disrupt and to improve drug development
      pathways.

PMID- 30224948
TI  - Unicameral bone cysts: Current concepts.
AB  - Unicameral bone cysts (UBC) or simple/solitary bone cysts are benign fluid filled
      cavities that enlarge over time, resulting in thinning of the bone. Usually these
      cysts are reported in the metaphyseal areas of long bones with open physes. 85%
      of UBCs occur almost exclusively in children and adolescents. UBCs are more
      aggressive in the first decade of life and correspondingly the recurrence rate
      for these patients is four times that for adolescents. The proximal humerus and
      femur account for almost 90% of these cases. UBCs are classified as active when
      they are within 1 cm of the physis and latent as they progress to a diaphyseal
      location. Differential diagnoses for UBC include aneurysmal bone cyst, fibrous
      dysplasia, enchondroma, and intraosseous ganglia. By the time of skeletal
      maturity most UBCs tend to resolve. Nonoperative treatment may be a viable option
      for many patients with small or symptomatic lesions. Interventions include
      steroid injection, open curettage and bone grafting, decompression and
      percutaneous injection of marrow or graft substitutes.

PMID- 30224949
TI  - Single-incision laparoscopic preperitoneal mesh repair of supra-pubic incisional
      hernia: A case report.
AB  - Introduction: Repair of supra-pubic incisional hernia is still challenging
      because of the highest pressure at the lower abdominal wall in the erect
      position. Recently, laparoscopic preperitoneal mesh repair has been gradually
      reported. Case presentation: A 77-year-old woman underwent single-incision
      laparoscopic preperitoneal mesh repair under a diagnosis of a supra-pubic
      incisional hernia, measuring 7 * 4 cm. A single, 2.5-cm, intraumbilical incision
      was made, followed by creation of the preperitoneal space. Then, the posterior
      rectus sheath and peritoneum were opened, and laparoscopic exploration was
      performed. After dissection of the supra-pubic hernia content, the tube for
      degassing the abdominal cavity was inserted into the abdominal cavity, and the
      peritoneum and the posterior sheath were closed. The preperitoneal space was
      dissected gradually, and circular dissection of the hernia sac was performed. The
      proximal sac (peritoneum) was sutured continuously. A 15 * 10 cm mesh was placed
      in the preperitoneal space and fixed securely with absorbable tacks at the pubic
      bone, Cooper's ligament, and the rectus abdominis muscle, respectively. After
      degassing the preperitoneal space, a second laparoscopic exploration was
      performed to confirm the secure suture of the peritoneum and no injury of the
      abdominal organs. At 4-month follow-up, the patient remained well with no signs
      of recurrence. Discussion: Single-incision laparoscopic preperitoneal mesh repair
      could minimize the recurrence of supra-umbilical incisional hernia and
      perioperative complications. Conclusion: Single-incision laparoscopic
      preperitoneal mesh repair, offering good cosmetic results, might be useful for
      repair of supra-pubic incisional hernia.

PMID- 30224950
TI  - Safety and tolerability of intrathecal liposomal amphotericin B (AmBisome) for
      cryptococcal meningitis: a retrospective study in HIV-infected patients.
AB  - Background: While mortality of HIV-related cryptococcal meningitis (CM) in
      developed countries is relatively low, in developing countries over half of
      patients die within 10 weeks. Current recommended therapies are often not
      suitable for resource-poor settings, and new shorter regimens are urgently
      needed. Intrathecal administration of liposomal amphotericin B (lAmB) has shown
      promising results in animal models. However, the safety and tolerability of
      intrathecal lAmB in humans are not well known. Methods: In this retrospective
      observational study, we report the tolerability and safety of intrathecal lAmB in
      patients with CM from an HIV cohort study in India. Results: In all, 18 patients
      were included in the analysis. Six were female and the median age was 40 years
      [interquartile range (IQR): 35-45]. The median CD4 count was 42 cells/ul (IQR: 19
      127). Compared with a historical control group, the hazard ratio for mortality
      was 0.59 (95% confidence interval: 0.26-1.29). Two patients complained of
      transient lumbar pain in single occasion. One patient had a skin reaction to
      chlorhexidine, which was used as skin disinfectant. After initial improvement,
      one patient requested to stop lumbar punctures for the last 2 days of treatment.
      Conclusion: Intrathecal lAmB was safe and well tolerated in HIV-infected patients
      with CM.

PMID- 30224951
TI  - Optimal duration for continuation of statin therapy in bacteremic patients.
AB  - Background: Evidence suggests statins may improve survival in patients with
      bloodstream infections. However, there is no consensus on optimal timing and
      duration of exposure. Objectives: To quantify statin therapy duration associated
      with decreased mortality in bacteremic statin users. Methods: We conducted a case
      control study using OptumClinformaticsTM with matched Premier hospital data (1
      October 2009-31 March 2013). Cases who died during the hospitalization were
      matched 1:1 to survivors on disease risk scores (DRSs). Post-admission statin
      therapy duration was evaluated in patients with at least 90 days of pre-admission
      continuous statin use. Classification and regression tree (CART) analysis was
      conducted to identify the optimal duration of statin continuation which provided
      the lowest inpatient mortality. Logistic regression was used to calculate the
      odds of mortality. Results: We included 58 DRS matched pairs of cases and
      controls: 47 patients (41%) continued statin therapy during the hospital
      admission, 15 (32%) cases and 32 (68%) controls. The CART analysis partitioned
      the continuation of statin therapy at ?2 days, representing lower mortality for
      patients who continued statins for 2 days or more and higher mortality for
      patients who did not continue or remained on statins for only 1 day. Inpatient
      mortality was 76% lower among those with at least 2 days of continued statin use
      (odds ratio 0.24, 95% confidence interval 0.11-0.55). Conclusion: Among matched
      cases and controls with at least 90 days of baseline statin use prior to the
      admission, the continuation of statins for at least 2 days after admission
      demonstrated a survival benefit among bacteremic patients.

PMID- 30224952
TI  - Fanconi syndrome due to tenofovir disoproxil fumarate reversed by switching to
      tenofovir alafenamide fumarate in an HIV-infected patient.
AB  - A case of tenofovir-induced Fanconi syndrome in a patient receiving
      antiretroviral therapy for HIV infection, with resolution of the related
      electrolyte abnormalities upon switch from tenofovir disoproxil fumarate to
      tenofovir alafenamide fumarate, is reported. Tenofovir alafenamide fumarate, a
      novel prodrug of tenofovir containing significantly lower doses of tenofovir than
      tenofovir disoproxil fumarate, has been associated with a favourable renal
      profile compared to tenofovir disoproxil fumarate. Generally, the rare
      complication of tenofovir disoproxil fumarate-induced Fanconi syndrome is managed
      by cessation of tenofovir. There are limited reports of the impact of a switch
      strategy from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate,
      which may be necessary in patients unable to discontinue tenofovir.

PMID- 30224953
TI  - Incidental peritoneal tuberculosis: surgeon's dilemma in endemic regions.
AB  - Background: Peritoneal tuberculosis has varying clinical manifestations. The
      study was conducted to highlight the entity of incidental peritoneal
      tuberculosis. Diagnostic and therapeutic dilemma is likely to occur on detection
      of unexpected peritoneal nodules. Materials and methodology: Incidental
      peritoneal tuberculosis was defined as peritoneal tuberculosis (peritoneal
      tubercles or ascites) detected intraoperatively in patients undergoing surgical
      exploration for other indications with no preoperative suspicion of abdominal
      tuberculosis or active tubercular lesions anywhere in the body. Retrospective
      analysis of patients operated in our department from June 2016 to November 2017
      was performed. Results: Of the 409 patients operated, 5 patients (1.2%) had
      incidental peritoneal tuberculosis. The primary indication of surgery was
      laparoscopic cholecystectomy in three, restoration of bowel continuity in one and
      laparoscopic appendectomy in one. Two patients had remote history of
      antitubercular therapy for pulmonary and nodal tuberculosis, respectively. The
      three patients planned for laparoscopic cholecystectomy had their procedures
      deferred on suspicion of peritoneal carcinomatosis. Subsequently, all the three
      underwent cholecystectomy after completion of antitubercular treatment. None of
      the resected specimen (gallbladder/appendix/colon) had evidence of tuberculosis
      (acid fast bacilli positive or caseating granuloma). Antitubercular treatment for
      6 months was completed in all the patients with active peritoneal disease.
      Conclusion: Incidental peritoneal tuberculosis represents an uncommon form of
      peritoneal tuberculosis. Absence of prior tuberculosis does not preclude the
      diagnosis of peritoneal tuberculosis. In an endemic region of tuberculosis,
      surgeons must be aware of the entity on encountering such finding. Frozen section
      can help in guiding appropriate management.

PMID- 30224954
TI  - Atomic level three-dimensional structure of individual particles with XFELs.
AB  - Progress in single-particle three-dimensional imaging is discussed, with advances
      in both data-collection and data-handling techniques described.

PMID- 30224955
TI  - De novo protein structure determination by heavy-atom soaking in lipidic cubic
      phase and SIRAS phasing using serial synchrotron crystallography.
AB  - During the past few years, serial crystallography methods have undergone
      continuous development and serial data collection has become well established at
      high-intensity synchrotron-radiation beamlines and XFEL radiation sources.
      However, the application of experimental phasing to serial crystallography data
      has remained a challenging task owing to the inherent inaccuracy of the
      diffraction data. Here, a particularly gentle method for incorporating heavy
      atoms into micrometre-sized crystals utilizing lipidic cubic phase (LCP) as a
      carrier medium is reported. Soaking in LCP prior to data collection offers a new,
      efficient and gentle approach for preparing heavy-atom-derivative crystals
      directly before diffraction data collection using serial crystallography methods.
      This approach supports effective phasing by utilizing a reasonably low number of
      diffraction patterns. Using synchrotron radiation and exploiting the anomalous
      scattering signal of mercury for single isomorphous replacement with anomalous
      scattering (SIRAS) phasing resulted in high-quality electron-density maps that
      were sufficient for building a complete structural model of proteinase K at 1.9 A
      resolution using automatic model-building tools.

PMID- 30224956
TI  - Considerations for three-dimensional image reconstruction from experimental data
      in coherent diffractive imaging.
AB  - Diffraction before destruction using X-ray free-electron lasers (XFELs) has the
      potential to determine radiation-damage-free structures without the need for
      crystallization. This article presents the three-dimensional reconstruction of
      the Melbournevirus from single-particle X-ray diffraction patterns collected at
      the LINAC Coherent Light Source (LCLS) as well as reconstructions from simulated
      data exploring the consequences of different kinds of experimental sources of
      noise. The reconstruction from experimental data suffers from a strong artifact
      in the center of the particle. This could be reproduced with simulated data by
      adding experimental background to the diffraction patterns. In those simulations,
      the relative density of the artifact increases linearly with background strength.
      This suggests that the artifact originates from the Fourier transform of the
      relatively flat background, concentrating all power in a central feature of
      limited extent. We support these findings by significantly reducing the artifact
      through background removal before the phase-retrieval step. Large amounts of
      blurring in the diffraction patterns were also found to introduce diffuse
      artifacts, which could easily be mistaken as biologically relevant features.
      Other sources of noise such as sample heterogeneity and variation of pulse energy
      did not significantly degrade the quality of the reconstructions. Larger data
      volumes, made possible by the recent inauguration of high repetition-rate XFELs,
      allow for increased signal-to-background ratio and provide a way to minimize
      these artifacts. The anticipated development of three-dimensional Fourier-volume
      assembly algorithms which are background aware is an alternative and
      complementary solution, which maximizes the use of data.

PMID- 30224957
TI  - Do the basic crystal chemistry principles agree with a plethora of recent quantum
      chemistry data?
AB  - The main descriptors of chemical bonding such as bond order (BO) and electron
      density at the bond critical point, rhoc, are customarily used to understand the
      crystal and electronic structure of materials, as well as to predict their
      reactivity and stability. They can be obtained in the framework of crystal
      chemistry and quantum chemistry approaches, which are mostly applied as
      alternatives to each other. This paper verifies the convergence of the two
      approaches by analyzing a plethora of quantum chemistry data available in the
      literature. The exponential correlation between the electron descriptors [BO ij
      and rhoc(ij)] and the length of chemical bonds, Rij , which is basic in crystal
      chemistry, was confirmed for 72 atom pairs, regardless of the nature of their
      interactions (ionic/covalent, metal-metal, etc.). The difference between the BO
      ij  (Rij ) correlations obtained in this work and those accepted in crystal
      chemistry for the same atomic pairs does not exceed the dispersion of quantum
      chemistry data, confirming the qualitative validity of the BO conservation
      principle. Various examples are presented to show that knowledge of the
      exponential parameters ensures a surprisingly simple determination of two basic
      electron descriptors in any complex compound with known interatomic distances. In
      particular, the BO analysis for 20 Re6-cluster complexes illustrates the BO
      conservation for systems with delocalized electrons. Despite the significant
      transfer of electron density from the Re-Re to the Re-ligand bonds, the total
      number of Re valence electrons used in bonding remains close to the formal value
      of seven electrons.

PMID- 30224958
TI  - Solving protein structure from sparse serial microcrystal diffraction data at a
      storage-ring synchrotron source.
AB  - In recent years, the success of serial femtosecond crystallography and the
      paucity of beamtime at X-ray free-electron lasers have motivated the development
      of serial microcrystallography experiments at storage-ring synchrotron sources.
      However, especially at storage-ring sources, if a crystal is too small it will
      have suffered significant radiation damage before diffracting a sufficient number
      of X-rays into Bragg peaks for peak-indexing software to determine the crystal
      orientation. As a consequence, the data frames of small crystals often cannot be
      indexed and are discarded. Introduced here is a method based on the expand
      maximize-compress (EMC) algorithm to solve protein structures, specifically from
      data frames for which indexing methods fail because too few X-rays are diffracted
      into Bragg peaks. The method is demonstrated on a real serial
      microcrystallography data set whose signals are too weak to be indexed by
      conventional methods. In spite of the daunting background scatter from the sample
      delivery medium, it was still possible to solve the protein structure at 2.1 A
      resolution. The ability of the EMC algorithm to analyze weak data frames will
      help to reduce sample consumption. It will also allow serial microcrystallography
      to be performed with crystals that are otherwise too small to be feasibly
      analyzed at storage-ring sources.

PMID- 30224959
TI  - Double role of metalloporphyrins in catalytic bioinspired supramolecular metal
      organic frameworks (SMOFs).
AB  - Heterogeneous catalysts are of great interest in many industrial processes for
      environmental reasons and, during recent years, a great effort has been devoted
      to obtain metal-organic frameworks (MOFs) with improved catalytic behaviour. Few
      supramolecular metal-organic frameworks (SMOFs) are stable under ambient
      conditions and those with anchored catalysts exhibit favourable properties.
      However, this paper presents an innovative approach that consists of using metal
      nodes as both structural synthons and catalysts. Regarding the latter,
      metalloporphyrins are suitable candidates to play both roles simultaneously. In
      fact, there are a number of papers that report coordination compounds based on
      metalloporphyrins exhibiting these features. Thus, the aim of this bioinspired
      work was to obtain stable SMOFs (at room temperature) based on metallo-porphyrins
      and explore their catalytic activity. This work reports the environmentally
      friendly microwave-assisted synthesis and characterization of the compound
      [H(bipy)]2[(MnTPPS)(H2O)2].2bipy.14H2O (TPPS = meso-tetra-phenyl-porphine
      4,4',4'',4'''-tetra-sulfonic acid and bipy = 4,4'-bi-pyridine). This compound is
      the first example of an MnTPPS-based SMOF, as far as we are aware, and has been
      structurally and thermally characterized through single-crystal X-ray
      diffraction, IR spectroscopy, thermogravimetry and transmission electron
      microscopy. Additionally, this work explores not only the catalytic activity of
      this compound but also of the compounds MU-O-[FeTCPP]2.16DMF and
      [CoTPPS0.5(bipy)(H2O)2].6H2O. The structural features of these supra-molecular
      materials, with accessible networks and high thermal stability, are responsible
      for their excellent behaviour as heterogeneous catalysts for different oxidation,
      condensation (aldol and Knoevenagel) and one-pot cascade reactions.

PMID- 30224960
TI  - Controlled usage of H/D exchange to circumvent concomitant polymorphs of ROY.
AB  - The hypothesis that H/D exchange affects the structural formation of organic
      compounds in the solid state is supported by a deeper understanding of the
      altering polymorphism of ROY (a substance striking for its high number of
      polymorphic forms) through deuteration. Therefore, ROY was deuterated at its
      amine function, which leads to a seemingly small yet effective modification of
      the hydrogen-bond strength. In contrast to the crystallization of the non
      deuterated ROY in methanol or ethanol, which leads to the simultaneous formation
      of two forms (OP and Y polymorphs), so-called concomitant polymorphs, the
      crystallization of d1-ROY leads to the selective formation of the Y polymorph
      exclusively. The preferred aggregation behavior of the Y form of d1-ROY is
      assigned to the weakening of an intramolecular hydrogen bond and a consequently
      strengthened intermolecular hydrogen bond after deuteration.

PMID- 30224962
TI  - Homology-based loop modeling yields more complete crystallographic protein
      structures.
AB  - Inherent protein flexibility, poor or low-resolution diffraction data or poorly
      defined electron-density maps often inhibit the building of complete structural
      models during X-ray structure determination. However, recent advances in
      crystallographic refinement and model building often allow completion of
      previously missing parts. This paper presents algorithms that identify regions
      missing in a certain model but present in homologous structures in the Protein
      Data Bank (PDB), and 'graft' these regions of interest. These new regions are
      refined and validated in a fully automated procedure. Including these
      developments in the PDB-REDO pipeline has enabled the building of 24 962 missing
      loops in the PDB. The models and the automated procedures are publicly available
      through the PDB-REDO databank and webserver. More complete protein structure
      models enable a higher quality public archive but also a better understanding of
      protein function, better comparison between homologous structures and more
      complete data mining in structural bioinformatics projects.

PMID- 30224961
TI  - Rapid sample delivery for megahertz serial crystallography at X-ray FELs.
AB  - Liquid microjets are a common means of delivering protein crystals to the focus
      of X-ray free-electron lasers (FELs) for serial femtosecond crystallography
      measurements. The high X-ray intensity in the focus initiates an explosion of the
      microjet and sample. With the advent of X-ray FELs with megahertz rates, the
      typical velocities of these jets must be increased significantly in order to
      replenish the damaged material in time for the subsequent measurement with the
      next X-ray pulse. This work reports the results of a megahertz serial diffraction
      experiment at the FLASH FEL facility using 4.3 nm radiation. The operation of gas
      dynamic nozzles that produce liquid microjets with velocities greater than 80 m s
      1 was demonstrated. Furthermore, this article provides optical images of X-ray
      induced explosions together with Bragg diffraction from protein microcrystals
      exposed to trains of X-ray pulses repeating at rates of up to 4.5 MHz. The
      results indicate the feasibility for megahertz serial crystallography
      measurements with hard X-rays and give guidance for the design of such
      experiments.

PMID- 30224963
TI  - The hydrocarbon-bearing clathrasil chibaite and its host-guest structure at low
      temperature.
AB  - The natural sII-type clathrasil chibaite [chemical formula SiO2.(M12,M16), where
      Mx denotes a guest mol-ecule] was investigated using single-crystal X-ray
      diffraction and Raman spectroscopy in the temperature range from 273 to 83 K. The
      O atoms of the structure at room temperature, which globally conforms to space
      group [V = 7348.9 (17) A3, a = 19.4420 (15) A], have anomalous anisotropic
      displacement parameters indicating a static or dynamic disorder. With decreasing
      temperature, the crystal structure shows a continuous symmetry-lowering
      transformation accompanied by twinning. The intensities of weak superstructure
      reflections increase as temperature decreases. A monoclinic twinned
      superstructure was derived at 100 K [A2/n, V = 7251.0 (17) A3, a' = 23.7054 (2),
      b' = 13.6861 (11), c' = 23.7051 (2) A, beta' = 109.47 degrees ]. The
      transformation matrix from the cubic to the monoclinic system is ai ' = (1/2 1
      1/2 / 1/2 0 -1/2 / 1/2 -1 1/2). The A2/n host framework has Si-O bond lengths and
      Si-O-Si angles that are much closer to known values for stable silicate-framework
      structures compared with the averaged model. As suggested from band splitting
      observed in the Raman spectra, the [512]-type cages (one crystallographically
      unique in , four different in A2/n) entrap the hydro-carbon species (CH4, C2H6,
      C3H8, i-C4H10). The [51264]-type cage was found to be unique in both structure
      types. It contains the larger hydro-carbon mol-ecules C2H6, C3H8 and i-C4H10.

PMID- 30224964
TI  - Twist and turn: a revised structural view on the unpaired bubble of class II CPD
      photolyase in complex with damaged DNA.
AB  - Cyclobutane pyrimidine dimer (CPD) photolyases harness the energy of blue light
      to repair UV-induced DNA CPDs. Upon binding, CPD photolyases cause the
      photodamage to flip out of the duplex DNA and into the catalytic site of the
      enzyme. This process, called base-flipping, induces a kink in the DNA, as well as
      an unpaired bubble, which are stabilized by a network of protein-nucleic acid
      interactions. Previously, several co-crystal structures have been reported in
      which the binding mode of CPD photolyases has been studied in detail. However, in
      all cases the internucleoside linkage of the photodamage site was a chemically
      synthesized formacetal analogue and not the natural phosphodiester. Here, the
      first crystal structure and conformational analysis via molecular-dynamics
      simulations of a class II CPD photolyase in complex with photodamaged DNA that
      contains a natural cyclobutane pyrimidine dimer with an intra-lesion
      phosphodiester linkage are presented. It is concluded that a highly conserved
      bubble-intruding region (BIR) mediates stabilization of the open form of CPD DNA
      when complexed with class II CPD photolyases.

PMID- 30224966
TI  - Bond orders for intermolecular interactions in crystals: charge transfer,
      ionicity and the effect on intramolecular bonds.
AB  - The question of whether intermolecular interactions in crystals originate from
      localized atom?atom interactions or as a result of holistic molecule?molecule
      close packing is a matter of continuing debate. In this context, the newly
      introduced Roby-Gould bond indices are reported for intermolecular 'sigma-hole'
      interactions, such as halogen bonding and chalcogen bonding, and compared with
      those for hydrogen bonds. A series of 97 crystal systems exhibiting these
      interaction motifs obtained from the Cambridge Structural Database (CSD) has been
      analysed. In contrast with conventional bond-order estimations, the new method
      separately estimates the ionic and covalent bond indices for atom?atom and
      molecule?molecule bond orders, which shed light on the nature of these
      interactions. A consistent trend in charge transfer from halogen/chalcogen bond
      acceptor to bond-donor groups has been found in these intermolecular interaction
      regions via Hirshfeld atomic partitioning of the electron populations. These
      results, along with the 'conservation of bond orders' tested in the interaction
      regions, establish the significant role of localized atom?atom interactions in
      the formation of these intermolecular binding motifs.

PMID- 30224965
TI  - Structural basis for light control of cell development revealed by crystal
      structures of a myxobacterial phytochrome.
AB  - Phytochromes are red-light photoreceptors that were first characterized in
      plants, with homologs in photosynthetic and non-photosynthetic bacteria known as
      bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert
      between two states denoted Pr and Pfr with distinct absorption spectra in the red
      and far-red. They have recently been engineered as enzymatic photoswitches for
      fluorescent-marker applications in non-invasive tissue imaging of mammals. This
      article presents cryo- and room-temperature crystal structures of the unusual
      phytochrome from the non-photosynthetic myxo-bacterium Stigmatella aurantiaca
      (SaBphP1) and reveals its role in the fruiting-body formation of this
      photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the
      chromophore-binding domain that stabilizes the Pr state in the classical BphPs.
      Instead it contains a threonine (Thr), a feature that is restricted to several
      myxobacterial phytochromes and is not evolutionarily understood. SaBphP1
      structures of the chromophore binding domain (CBD) and the complete photosensory
      core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the
      molecular mechanism of the Pr/Pfr transition associated with the physiological
      response of this myxobacterium to red light. Specifically, key structural
      differences in the CBD and PCM between the wild-type and the Thr-to-His mutant
      involve essential chromophore contacts with proximal amino acids, and point to
      how the photosignal is transduced through the rest of the protein, impacting the
      essential enzymatic activity in the photomorphogenic response of this
      myxobacterium.

PMID- 30224967
TI  - Exploring the simultaneous sigma-hole/pi-hole bonding characteristics of a Br?pi
      interaction in an ebselen derivative via experimental and theoretical electron
      density analysis.
AB  - In this study, the nature and characteristics of a short Br?pi interaction
      observed in an ebselen derivative, 2-(2-bromophenyl)benzo[d][1,2]selenazol-3(2H)
      one, has been explored. The electronic nature of this Br?pi interaction was
      investigated via high-resolution X-ray diffraction and periodic density
      functional theory calculations using atoms-in-molecules (AIM) analysis. This
      study unravels the simultaneous presence of sigma-hole and pi-hole bonding
      characteristics in the same interaction. The dual characteristics of this unique
      Br?pi interaction are further established via molecular electrostatic potentials
      (MESPs) and natural bond orbitals (NBOs).

PMID- 30224968
TI  - Comments on 'Hydrogen bonds in crystalline d-alanine: diffraction and
      spectroscopic evidence for differences between enantiomers'.
AB  - The recent paper by Belo, Pereira, Freire, Argyriou, Eckert & Bordallo [(2018 ?),
      IUCrJ, 5, 6-12] reports observations that may lead one to think of very strong
      and visible consequences of the parity-violation energy difference between
      enantiomers of a molecule, namely alanine. If proved, this claim would have an
      enormous impact for research in structural chemistry. However, alternative, more
      realistic, explanations of their experiments have not been ruled out by the
      authors. Moreover, the theoretical calculations carried out to support the
      hypothesis are unable to differentiate between enantiomers (molecules or
      crystals). Therefore, the conclusions drawn by Belo et al. (2018 ?) are deemed
      inappropriate as the data presented do not contain sufficient information to
      reach such a conclusion.

PMID- 30224969
TI  - Male infertility: the intracellular bacterial hypothesis.
AB  - Infertility is a disease that affects one in seven couples. As male infertility
      affects approximately 30% of these couples with an unknown cause in half the
      cases, it represents a major public health concern. The classic treatment of male
      infertility involves intrauterine insemination, with modest outcome, and in vitro
      fertilization with intracytoplasmic sperm injection, which is known to be
      invasive and expensive, without treating the specific cause of infertility. Male
      fertility is mainly evaluated through a semen assessment where abnormal
      parameters such as concentration and motility can be associated with a decreased
      chance of conception. Infectious processes represent plausible candidates for
      male infertility. Chlamydia trachomatis is well known to cause female infertility
      through tubal damage but its role in male infertility remains controversial. The
      link between ureaplasmas/mycoplasmas and male infertility is also debatable. The
      potential negative impact of these bacteria on male fertility might not only
      involve semen parameters but also, as with C. trachomatis, include important
      physiological mechanisms such as fertilization processes that are not routinely
      assessed during infertility investigation. Basic research is important to help
      determine the exact effect of these bacteria on male fertility to develop
      targeted treatment and go beyond in vitro fertilization with intracytoplasmic
      sperm injection.

PMID- 30224970
TI  - Utility of CHROMagar mSuperCARBA for surveillance cultures of carbapenemase
      producing Enterobacteriaceae.
AB  - Culture of carbapenemase-producing Enterobacteriaceae (CPE) as part of active
      surveillance is one of the most useful strategies for successful infection
      control programmes. Our objective was to compare the recently introduced
      CHROMagar mSuperCARBA agar for CPE detection in surveillance cultures from
      perineal swabs with the US Centers for Disease Control and Prevention method. Our
      results showed that this agar is a useful and affordable alternative (sensitivity
      93.05%, specificity 96.21%, diagnostic accuracy 95.2%) to detect CPE in hospital
      settings.

PMID- 30224971
TI  - Evaluation of visual triage for screening of Middle East respiratory syndrome
      coronavirus patients.
AB  - The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in
      September 2012 in Saudi Arabia had attracted the attention of the global health
      community. In 2017 the Saudi Ministry of Health released a visual triage system
      with scoring to alert healthcare workers in emergency departments (EDs) and
      haemodialysis units for the possibility of occurrence of MERS-CoV infection. We
      performed a retrospective analysis of this visual score to determine its
      sensitivity and specificity. The study included all cases from 2014 to 2017 in a
      MERS-CoV referral centre in Riyadh, Saudi Arabia. During the study period there
      were a total of 2435 suspected MERS cases. Of these, 1823 (75%) tested negative
      and the remaining 25% tested positive for MERS-CoV by PCR assay. The application
      of the visual triage score found a similar percentage of MERS-CoV and non-MERS
      CoV patients, with each score from 0 to 11. The percentage of patients with a
      cutoff score of >=4 was 75% in patients with MERS-CoV infection and 85% in
      patients without MERS-CoV infection (p 0.0001). The sensitivity and specificity
      of this cutoff score for MERS-CoV infection were 74.1% and 18.6%, respectively.
      The sensitivity and specificity of the scoring system were low, and further
      refinement of the score is needed for better prediction of MERS-CoV infection.

PMID- 30224972
TI  - First report of colistin resistance among carbapenem-resistant Acinetobacter
      baumannii isolates recovered from hospitalized patients in Egypt.
AB  - Acinetobacter baumannii is an opportunistic pathogen that poses an increasing
      threat in the health-care community. Colistin is one of the promising options for
      treatment of multidrug-resistant A. baumannii. The current study investigated the
      emergence of colistin resistance among carbapenem-resistant strains of A.
      baumannii in Egypt. It involved identification of clinically recovered A.
      baumannii isolates using the VITEK-2 system, and screening of their antimicrobial
      susceptibilities using broth microdilution techniques. Characterizations of
      carbapenemase and 16S rRNA methyltransferase genes were performed using PCR.
      Colistin-resistance determinants were characterized by sequencing. Carbapenem
      resistant A. baumannii isolates (n = 40) showed resistance to amoxicillin
      clavulanic acid, cefotaxime, gentamicin and amikacin. Most isolates revealed
      resistance to ciprofloxacin (95%; n = 38) and co-trimoxazole (92.5%; n = 37).
      Resistance to tobramycin and doxycycline was 80% (n = 32) and 62.5% (n = 25),
      respectively. Only two A. baumannii isolates demonstrated colistin resistance.
      Carbapenemase activity was tested by modified Hodge test and 78% of isolates were
      positive. All isolates carried blaOXA-51-like genes whereas bla-OXA-23 was
      detected in 80% (n = 32) of isolates. Among 16S rRNA methylase genes, armA was
      detected in 22.5% (n = 9) of the isolates. Analyses of lpxA, lpxC, lpxD and
      pmrCAB genetic sequences suggest that colistin resistance could be attributed to
      mutations in pmrCAB genes. Alarmingly, colistin resistance was associated with
      high levels of resistance to other antimicrobials. The current findings represent
      a serious health-care problem capable of restraining future therapeutic options.

PMID- 30224973
TI  - Incidence Rate of Post-Kidney Transplant Infection: A Retrospective Cohort Study
      Examining Infection Rates at a Large Canadian Multicenter Tertiary-Care Facility.
AB  - Background: Reducing post-operative infections among kidney transplant patients
      is critical to improve long-term outcomes. With shifting disease demographics and
      implementation of new transplantation protocols, frequent evaluation of infection
      rate and type is necessary. Objective: Our objectives were to assess the
      incidence and types of post-operative infections in kidney transplant recipients
      at a large tertiary-care facility and determine sample sizes needed for future
      intervention trials. Design: Retrospective cohort study. Setting: The Ottawa
      Hospital, Ottawa, Ontario. Patients: Adult kidney transplant patients, N = 142.
      Measurements: Demographic data, transplant protocol, infections up to 2 years
      following transplantation. Methods: Infections within 2 years following
      transplantation in all kidney transplant recipients between January 2011 and
      December 2012 were reviewed. Sample sizes were determined using all-cause
      infection rates and infection-free survival data. Results: Of 142 patients, 44
      (31.0%) had at least one infection. The incidence of infection was 36.2 per 100
      patient-years by 2 years post-transplant. A total of 32 (22.5%) patients had 56
      infection-related hospitalizations with 73.2% occurring in the first year. In the
      first 2 years, urinary tract infections had the highest incidence (18.1 per 100
      patient-years) followed by skin (3.9 per 100 patient-years), cytomegalovirus (3.9
      per 100 patient-years), and bacteremia (3.9 per 100 patient-years). Results
      indicate that 206 patients per study arm would be needed to show a 30% reduction
      in the 2-year incidence of infection post-transplantation. Limitations: Infection
      rates may be slightly underestimated due to the relatively short 2-year follow
      up; however, the highest infection-risk period was captured within this time
      frame. Conclusions: Infections post-kidney transplant are still common,
      particularly urinary tract infections. They are associated with significant
      morbidity and hospitalization. Given the feasible sample sizes calculated in this
      study, intervention trials are indicated to further reduce infection rates within
      the first 2 years post-kidney transplantation.

PMID- 30224974
TI  - Implicit and explicit influences of religious cognition on Dictator Game
      transfers.
AB  - Does religion promote prosocial behaviour? Despite numerous publications that
      seem to answer this question affirmatively, divergent results from recent meta
      analyses and pre-registered replication efforts suggest that the issue is not yet
      settled. Uncertainty lingers around (i) whether the effects of religious
      cognition on prosocial behaviour were obtained through implicit cognitive
      processes, explicit cognitive processes or both and (ii) whether religious
      cognition increases generosity only among people disinclined to share with
      anonymous strangers. Here, we report two experiments designed to address these
      concerns. In Experiment 1, we sought to replicate Shariff and Norenzayan's
      demonstration of the effects of implicit religious priming on Dictator Game
      transfers to anonymous strangers; unlike Shariff and Norenzayan, however, we used
      an online environment where anonymity was virtually assured. In Experiment 2, we
      introduced a 'taking' option to allow greater expression of baseline selfishness.
      In both experiments, we sought to activate religious cognition implicitly and
      explicitly, and we investigated the possibility that religious priming depends on
      the extent to which subjects view God as a punishing, authoritarian figure.
      Results indicated that in both experiments, religious subjects transferred more
      money on average than did non-religious subjects. Bayesian analyses supported the
      null hypothesis that implicit religious priming did not increase Dictator Game
      transfers in either experiment, even among religious subjects. Collectively, the
      two experiments furnished support for a small but reliable effect of explicit
      priming, though among religious subjects only. Neither experiment supported the
      hypothesis that the effect of religious priming depends on viewing God as a
      punishing figure. Finally, in a meta-analysis of relevant studies, we found that
      the overall effect of implicit religious priming on Dictator Game transfers was
      small and did not statistically differ from zero.

PMID- 30224975
TI  - Identification and quantification of spinochromes in body compartments of
      Echinometra mathaei's coloured types.
AB  - Sea urchin pigmentation is mainly due to polyhydroxy-1,4-naphthoquinones called
      spinochromes. If their molecular structures are well known in test and spines of
      many species, their abundance and distribution in other body compartments remain
      unstudied. The aim of this study is to analyse the pigment composition in four
      body compartments (test/spines, digestive system, gonads and coelomic fluid) of
      four coloured types of the sea urchin Echinometra mathaei. Qualitative and
      quantitative measurements by mass spectrometry highlight the existence of 13
      different pigments; among which are five isomers of known spinochromes as well as
      three potentially new ones. The composition comparison shows the largest
      spinochrome diversity in 'test/spines' body compartments. The spinochrome
      concentrations vary from 48 to 1279 mg kg-1 of dried body compartment. It is the
      highest in the digestive system, although it is also important in the organic
      fraction of the 'test/spines' body compartment. This observation may be explained
      by higher exposures of some body compartments to external environments and by the
      protective role fulfilled by spinochromes against microorganisms, ultraviolet
      radiation and reactive oxygen species. The 'black' type-the most common coloured
      type in coral reefs-has the highest concentration of spinochromes indicating
      their importance in Echinoids' fitness by acting as a protective agent.

PMID- 30224976
TI  - Behaviourally mediated predation avoidance in penguin prey: in situ evidence from
      animal-borne camera loggers.
AB  - Predator dietary studies often assume that diet is reflective of the diversity
      and relative abundance of their prey. This interpretation ignores species
      specific behavioural adaptations in prey that could influence prey capture. Here,
      we develop and describe a scalable biologging protocol, using animal-borne camera
      loggers, to elucidate the factors influencing prey capture by a seabird, the
      gentoo penguin (Pygoscelis papua). From the video evidence, we show, to our
      knowledge for the first time, that aggressive behavioural defence mechanisms by
      prey can deter prey capture by a seabird. Furthermore, we provide evidence
      demonstrating that these birds, which were observed hunting solitarily, target
      prey when they are most discernible. Specifically, birds targeted prey primarily
      while ascending and when prey were not tightly clustered. In conclusion, we show
      that prey behaviour can significantly influence trophic coupling in marine
      systems because despite prey being present, it is not always targeted. Thus,
      these predator-prey relationships should be accounted for in studies using marine
      top predators as samplers of mid- to lower trophic-level species.

PMID- 30224977
TI  - Marsupial chromosome DNA content and genome size assessed from flow karyotypes:
      invariable low autosomal GC content.
AB  - Extensive chromosome homologies revealed by cross-species chromosome painting
      between marsupials have suggested a high level of genome conservation during
      evolution. Surprisingly, it has been reported that marsupial genome sizes vary by
      more than 1.2 Gb between species. We have shown previously that individual
      chromosome sizes and GC content can be measured in flow karyotypes, and have
      applied this method to compare four marsupial species. Chromosome sizes and GC
      content were calculated for the grey short-tailed opossum (2n = 18), tammar
      wallaby (2n = 16), Tasmanian devil (2n = 14) and fat-tailed dunnart (2n = 14),
      resulting in genome sizes of 3.41, 3.31, 3.17 and 3.25 Gb, respectively. The
      findings under the same conditions allow a comparison between the four species,
      indicating that the genomes of these four species are 1-8% larger than human. We
      show that marsupial genomes are characterized by a low GC content invariable
      between autosomes and distinct from the higher GC content of the marsupial *
      chromosome.

PMID- 30224979
TI  - Synthesis of citric acid-modified resins and their adsorption properties towards
      metal ions.
AB  - Types of resins anchored on citric acid were synthesized and identified. The
      citric acid-modified resins PS-CA, PS-O-CA and PS-N-CA were synthesized by
      anchoring citric acid on PS-Cl, PS-OH and PS-NH2, respectively. The PS-CA, PS-O
      CA and PS-N-CA were used to adsorb Fe3+, Al3+, Cu2+, Pb2+, Cd2+ and Hg2+. The
      influences of pH, adsorption time and metal ion concentration on the adsorption
      capacities of the resins were investigated. After optimization, PS-CA was a good
      adsorbent to Fe3+, Cu2+, Pb2+ and Cd2+ with qm values of 143.9 mg g-1, 77.4 mg g
      1, 18.9 mg g-1 and 119.9 mg g-1, respectively. PS-N-CA was a good adsorbent to
      Al3+ and Hg2+ with qm values of 176.6 mg g-1 and 114.9 mg g-1, respectively. The
      adsorption kinetics and adsorption isotherm experiments indicated that the pseudo
      first-order rate equation was more appropriate for characterizing the kinetic
      data and the Langmuir model was more suitable for fitting the equilibrium data.
      The reusability of the citric acid-modified resins was also evaluated and these
      resins exhibited considerable reusability.

PMID- 30224978
TI  - A mathematical understanding of how cytoplasmic dynein walks on microtubules.
AB  - Cytoplasmic dynein 1 (hereafter referred to simply as dynein) is a dimeric motor
      protein that walks and transports intracellular cargos towards the minus end of
      microtubules. In this article, we formulate, based on physical principles, a
      mechanical model to describe the stepping behaviour of cytoplasmic dynein walking
      on microtubules from the cell membrane towards the nucleus. Unlike previous
      studies on physical models of this nature, we base our formulation on the whole
      structure of dynein to include the temporal dynamics of the individual subunits
      such as the cargo (for example, an endosome, vesicle or bead), two rings of six
      ATPase domains associated with diverse cellular activities (AAA+ rings) and the
      microtubule-binding domains which allow dynein to bind to microtubules. This
      mathematical framework allows us to examine experimental observations on dynein
      across a wide range of different species, as well as being able to make
      predictions on the temporal behaviour of the individual components of dynein not
      currently experimentally measured. Furthermore, we extend the model framework to
      include backward stepping, variable step size and dwelling. The power of our
      model is in its predictive nature; first it reflects recent experimental
      observations that dynein walks on microtubules using a weakly coordinated
      stepping pattern with predominantly not passing steps. Second, the model predicts
      that interhead coordination in the ATP cycle of cytoplasmic dynein is important
      in order to obtain the alternating stepping patterns and long run lengths seen in
      experiments.

PMID- 30224981
TI  - Quantifying layer similarity in multiplex networks: a systematic study.
AB  - Computing layer similarities is an important way of characterizing multiplex
      networks because various static properties and dynamic processes depend on the
      relationships between layers. We provide a taxonomy and experimental evaluation
      of approaches to compare layers in multiplex networks. Our taxonomy includes,
      systematizes and extends existing approaches, and is complemented by a set of
      practical guidelines on how to apply them.

PMID- 30224980
TI  - The multiple roles of beta-diversity help untangle community assembly processes
      affecting recovery of temperate rocky shores.
AB  - Metacommunity theory highlights the potential of beta-diversity as a useful link
      to empirical research, especially in diverse systems where species exhibit a
      range of stage-dependent dispersal characteristics. To investigate the importance
      of different components and scales of beta-diversity in community assembly, we
      conducted a large-scale disturbance experiment and compared relative recovery
      across multiple sites and among plots within sites on the rocky shore. Six sites
      were spread along 80 km of coastline and, at each site, five plots were
      established, matching disturbed and undisturbed quadrats. Recovery was not
      complete at any of the sites after 1 year for either epibenthos (mostly composed
      of macroalgae and, locally, mussels) or infauna. Significant differences in
      recovery among sites were observed for epibenthos but not for infauna, suggesting
      that different community assembly processes were operating. This was supported by
      epibenthos in the recovering plots having higher species turnover than in
      undisturbed sediment, and recovery well predicted by local diversity, while
      infaunal recovery was strongly influenced by the epibenthic community's habitat
      complexity. However, infaunal community recovery did not simply track formation
      of habitat by recovering epibenthos, but appeared to be overlain by within-site
      and among-site aspects of infaunal beta-diversity. These results suggest that
      documenting changes in the large plants and animals alone will be a poor
      surrogate for rocky shore community assembly processes. No role for ecological
      connectivity (negative effect of among-site beta-diversity) in driving recovery
      was observed, suggesting a low risk of effects from multiple disturbances
      propagating along the coast, but a limited resilience at the site scale to large
      scale disturbances such as landslides or oil spills.

PMID- 30224982
TI  - The contribution of nano-zinc to alleviate salinity stress on cotton plants.
AB  - To investigate the effect of nano-zinc fertilizer on growth, yield and mineral
      status of cotton plants grown under salt stress, a pot experiment was set up in
      the greenhouse of the National Research Centre. The treatments were as follows:
      (I) diluted seawater: 10% (S1), 20% (S2) and tap water as a control (S0), (II)
      100 ppm (NZn1), 200 ppm (NZn2) nano-zinc and distilled water as a control (NZn0).
      Irrigation with 10 and 20% seawater decreased dry weight (DW) of leaves by 11.53
      and 43.22%, while decreases in bolls were 15.50 and 71.65%, respectively. Except
      for root DW and top/root ratio, the measured growth parameters were increased as
      nano-zinc concentration increased. As for the interaction between treatments, the
      highest DW of stem, leaves and bolls resulted from the addition of NZn2 under
      normal condition, followed by NZn2 x S1 and the next was NZn2 x S2. The foliar
      application of 200 ppm nano-Zn led to mitigating the adverse effect of salinity
      and confirmed that diluted seawater could be used in the irrigation of cotton
      plant. However, phosphorus fertilizer should be added with nano-Zn application to
      avoid P/Zn imbalance. Some elements' status and their ratios were recorded.

PMID- 30224983
TI  - Polarized Ukraine 2014: opinion and territorial split demonstrated with the
      bounded confidence XY model, parametrized by Twitter data.
AB  - Multiple countries have recently experienced extreme political polarization,
      which, in some cases, led to escalation of hate crime, violence and political
      instability. Besides the much discussed presidential elections in the USA and
      France, Britain's Brexit vote and Turkish constitutional referendum showed signs
      of extreme polarization. Among the countries affected, Ukraine faced some of the
      gravest consequences. In an attempt to understand the mechanisms of these
      phenomena, we here combine social media analysis with agent-based modelling of
      opinion dynamics, targeting Ukraine's crisis of 2014. We use Twitter data to
      quantify changes in the opinion divide and parametrize an extended bounded
      confidence XY model, which provides a spatio-temporal description of the
      polarization dynamics. We demonstrate that the level of emotional intensity is a
      major driving force for polarization that can lead to a spontaneous onset of
      collective behaviour at a certain degree of homophily and conformity. We find
      that the critical level of emotional intensity corresponds to a polarization
      transition, marked by a sudden increase in the degree of involvement and in the
      opinion bimodality.

PMID- 30224985
TI  - Characterization of biocarbon generated by high- and low-temperature pyrolysis of
      soy hulls and coffee chaff: for polymer composite applications.
AB  - The physical properties of biocarbon vary widely with the biomass used, and the
      temperature and duration of pyrolysis. This study identifies the effects of
      feedstock characteristics and pyrolysis conditions on the production of biocarbon
      and the corresponding properties for industrial applications. For coffee chaff
      and soy hulls, ash content and carbon content increased with pyrolysis
      temperature and duration. Ash content increased thermal conductivity and specific
      heat, and decreased electrical conductivity. Change in surface area with
      pyrolysis conditions was dependent on type of feedstock. Increased surface area
      corresponded with increased thermal and electrical conductivity. Increased carbon
      content corresponded with increased graphitization and thermal stability and
      decreased surface functionality. Properties of soy hull biocarbons were found to
      be similar to the properties of other biocarbons with industrial applications
      such as incorporation into polymer composites.

PMID- 30224984
TI  - Fluorimetric detection of reserpine in mouse serum through online post-column
      electrochemical derivatization.
AB  - A novel method combining high-performance liquid chromatography with online post
      column electrochemical derivatization and fluorescence detection was established
      for the detection of reserpine in mouse serum. Reserpine separation was conducted
      using a C18 column with 5 mM H3PO4 and acetonitrile (55/45, v/v) as eluent.
      Reserpine was then electro-oxidized into a strongly fluorescent compound using an
      electrolytic cell device. Detection parameters, such as potential and
      fluorescence wavelength, were optimized. The linearity of the proposed method
      ranged from 0.01 to 5.0 mg l-1 with a correlation coefficient of 0.9997. The
      limit of qualification (S/N = 10) and limit of detection (S/N = 3) were 9.7 and
      2.9 ug l-1, respectively. Resperine recoveries from spiked blank and drug-treated
      mouse serum samples ranged from 92.0 to 115%.

PMID- 30224986
TI  - An experimental study on coflow diffusion combustion in a pellet-packed bed with
      different bed lengths.
AB  - In experimental investigations on axial symmetry, over-ventilated CH4/air
      diffusion combustion in a packed bed is executed to study the height, shape and
      stability of the flame. The combustor is a quartz tube packed with alumina
      pellets in which a cylindrical fuel stream is surrounded by a coflow air nozzle.
      The results show that the bed length and pellet diameter have a significant
      influence on the flame properties. In general, the flame above the pellet surface
      has axial symmetry, and its shape and colour are similar to those of a
      conventional diffusion flame when the bed length is smaller. The colour of the
      flame front varies with the bed length. The changed colour indicates an increased
      flame front temperature and that the combustion regime above the bed surface may
      change from non-premixed combustion to partially premixed combustion or even
      premixed combustion owing to the mix and dispersion effect in the packed bed. In
      addition, multiple flame behaviours, such as an inclined flame front, isolated
      reaction zone and oscillatory motion followed by a pulsating sound with a few
      hertz in a packed bed, are observed experimentally. The possible reasons for
      these phenomena are discussed.

PMID- 30224987
TI  - Enhanced in vitro biocompatibility and osteogenesis of titanium substrates
      immobilized with dopamine-assisted superparamagnetic Fe3O4 nanoparticles for
      hBMSCs.
AB  - Titanium (Ti) is an ideal bone substitute due to its superior bio-compatibility
      and remarkable corrosion resistance. However, in order to improve the
      osteoconduction and osteoinduction capacities in clinical applications, different
      kinds of surface modifications are typically applied to Ti alloys. In this study,
      we fabricated a tightly attached polydopamine-assisted Fe3O4 nanoparticle coating
      on Ti with magnetic properties, aiming to improve the osteogenesis of the Ti
      substrates. The PDA-assisted Fe3O4 nanoparticle coatings were characterized by
      scanning electron microscopy, energy dispersive spectroscopy, atomic force
      microscopy and water contact angle measurements. The cell attachment and
      proliferation rate of the human bone mesenchymal stem cells (hBMSCs) on the Ti
      surface significantly improved with the Fe3O4/PDA coating when compared with the
      pure Ti without a coating. Furthermore, the results of in vitro alkaline
      phosphatase (ALP) activity at 7 and 14 days and alizarin red S staining at 14
      days showed that the Fe3O4/PDA coating on Ti promoted the osteogenic
      differentiation of hBMSCs. Moreover, hBMSCs co-cultured with the Fe3O4/PDA-coated
      Ti for approximately 14 days also exhibited a significantly higher mRNA
      expression level of ALP, osteocalcin and runt-related transcription factor-2
      (RUNX2). Our in vitro results revealed that the present PDA-assisted Fe3O4
      nanoparticle surface coating is an innovative method for Ti surface modification
      and shows great potential for clinical applications.

PMID- 30224988
TI  - A three-dimensionally preserved lobopodian from the Herefordshire (Silurian)
      Lagerstatte, UK.
AB  - The Herefordshire (Silurian) Lagerstatte (approx. 430 Myr BP) has yielded, among
      many exceptionally preserved invertebrates, a wide range of new genera belonging
      to crown-group Panarthropoda. Here, we increase this panarthropod diversity with
      the lobopodian Thanahita distos, a new total-group panarthropod genus and
      species. This new lobopodian preserves at least nine paired, long, slender
      appendages, the anterior two in the head region and the posterior seven
      representing trunk lobopods. The body ends in a short post-appendicular
      extension. Some of the trunk lobopods bear two claws, others a single claw. The
      body is covered by paired, tuft-like papillae. Thanahita distos joins only seven
      other known three-dimensionally preserved lobopodian or onychophoran (velvet
      worm) fossil specimens and is the first lobopodian to be formally described from
      the Silurian. Phylogenetic analysis recovered it, together with all described
      Hallucigenia species, in a sister-clade to crown-group panarthropods. Its
      placement in a redefined Hallucigeniidae, an iconic Cambrian clade, indicates the
      survival of this clade to Silurian times.

PMID- 30224989
TI  - A liver health hui: hepatitis C knowledge and associated risk factors in New
      Zealand gang members and their families.
AB  - Hepatitis C virus (HCV) and B virus (HBV) infections are highly prevalent, with a
      high percentage of undiagnosed cases. Knowledge of HCV and its modes of
      transmission are essential for disease prevention and management. We studied a
      high-risk New Zealand gang population on viral hepatitis prevalence, their level
      of knowledge and the liver health risk factors in a community setting.
      Participants completed demographic, risk factor and knowledge questionnaires in
      three health meetings in New Zealand. Participants' blood samples were tested for
      HBV, HCV, biochemical indicators of liver disease. Liver fibrosis levels were
      assessed using a Fibroscan(r) device. We studied 52 adult Mongrel Mob members,
      affiliates and whanau (extended family) throughout New Zealand. We identified no
      HCV and two HBV cases, confirmed high-risk factor levels and poor associated
      knowledge, with a significant association between lack of knowledge and presence
      of specific risk factors. We successfully conducted a community-focused, high
      risk, hard-to-reach gang population study, and found a link between lack of
      knowledge and risk factors for HCV infection. This study provided first-of-its
      kind data on viral hepatitis in a gang population and demonstrated the need for
      educational screening programmes to aid early HCV detection, prevention and
      treatment.

PMID- 30224991
TI  - Characterizations and morphology of sodium tungstate particles.
AB  - A solid-state reaction technique was used to synthesize polycrystalline Na2WO4.
      Preliminary X-ray studies revealed that the compound has a cubic structure at
      room temperature. The formation of the compound has been confirmed by X-ray
      powder diffraction studies and Raman spectroscopy. Electrical and dielectric
      properties of the compound have been studied using complex impedance spectroscopy
      in the frequency range 209 Hz-1 MHz and temperature range 586-679 K. The
      impedance data were modellized by an equivalent circuit consisting of series of a
      combination of grains and grains boundary. We use complex electrical modulus M*
      at various temperatures to analyse dielectric data. The modulus plots are
      characterized by the presence of two relaxation peaks thermally activated. The
      morphologies and the average particle size of the resultant sodium tungstate
      sample were demonstrated by atomic force microscopy, scanning electron microscopy
      and transmission electron microscopy. The thicknesses and optical constants of
      the sample have been calculated using ellipsometric measurements in the range of
      200-22 000 nm by means of new amorphous dispersion formula which is the objective
      of the present work. The results were obtained for Na2WO4 particles from
      experimental (EXP) and measured (FIT) data showed an excellent agreement. In
      addition, the energy gap of the Na2WO4 sample has been determined using
      ellipsometry and confirmed by spectrophotometry measurements.

PMID- 30224990
TI  - How does human motor cortex regulate vocal pitch in singers?
AB  - Vocal pitch is used as an important communicative device by humans, as found in
      the melodic dimension of both speech and song. Vocal pitch is determined by the
      degree of tension in the vocal folds of the larynx, which itself is influenced by
      complex and nonlinear interactions among the laryngeal muscles. The relationship
      between these muscles and vocal pitch has been described by a mathematical model
      in the form of a set of 'control rules'. We searched for the biological
      implementation of these control rules in the larynx motor cortex of the human
      brain. We scanned choral singers with functional magnetic resonance imaging as
      they produced discrete pitches at four different levels across their vocal range.
      While the locations of the larynx motor activations varied across singers, the
      activation peaks for the four pitch levels were highly consistent within each
      individual singer. This result was corroborated using multi-voxel pattern
      analysis, which demonstrated an absence of patterned activations differentiating
      any pairing of pitch levels. The complex and nonlinear relationships between the
      multiple laryngeal muscles that control vocal pitch may obscure the neural
      encoding of vocal pitch in the brain.

PMID- 30224992
TI  - Seasonal characteristics of phosphorus sorption by sediments from plain lakes
      with different trophic statuses.
AB  - Phosphorus (P) sorption in sediments plays a significant role in trophic status
      of a lake. This study investigated the characteristics of P sorption in sediments
      from three lakes with different trophic statuses (moderately eutrophic, lightly
      eutrophic and moderately trophic) through kinetic, batch equilibrium and
      thermodynamic experiments. Results show that pseudo-second-order kinetics best
      describe P sorption in sediments from the three lakes. Fitting by modified
      Langmuir and Freundlich isotherms indicates that the moderately trophic lake
      sediment has higher sorption capacity (maximum of 0.848 mg g-1 at 35 degrees C)
      than the sediments of the other two lakes at different temperatures (5, 15, 25
      and 35 degrees C). Thermodynamic results indicate that the processes of P
      sorption of the three sediments are spontaneous, entropy-driven and endothermic
      reactions. The risk of P release in sediments was analysed according to the
      calculated results of isotherms combined with the change in P fraction. Sediments
      from the moderately eutrophic lake act as a source in summer. The lightly
      eutrophic and moderately trophic lakes act as sources in spring and winter, and a
      pool in summer and autumn, respectively. Furthermore, the amounts of reductant
      soluble P, calcium-bound P and iron-bound P are significantly related to the
      sorption capacity of sediments from the three lakes (p < 0.05). The different
      sediments have different P release risk, and P fraction in sediment is one of the
      significant factors of P sorption.

PMID- 30224993
TI  - Room-temperature excitonic emission with a phonon replica from graphene
      nanosheets deposited on Ni-nanocrystallites/Si-nanoporous pillar array.
AB  - Graphene nanosheets (GNSs) were grown on a Si nanoporous pillar array (Si-NPA)
      via chemical vapour deposition, using a thin layer of pre-deposited Ni
      nanocrystallites as catalyst. GNSs were determined to be of high quality and good
      dispersivity, with a typical diameter size of 15 * 8 nm. Light absorption
      measurements showed that GNSs had an absorption band edge at 3.3 eV. They also
      showed sharp and regular excitonic emitting peaks in the ultraviolet and visible
      region (2.06-3.6 eV). Moreover, phonon replicas with long-term stability appeared
      with the excitonic peaks at room temperature. Temperature-dependent
      photoluminescence from the GNSs revealed that the excitonic emission derived from
      free and bound excitonic recombination. A physical model based on band energy
      theory was constructed to analyse the carrier transport of GNSs. The Ni
      nanocrystallites on Si-NPA, which acted as a metal-enhanced fluorescence
      substrate, were supposed to accelerate the excitonic recombination of GNSs and
      enhanced the measured emission intensity. Results of this study would be valuable
      in determining the luminescence mechanism of GNSs and could be applied in real
      world optoelectronic devices.

PMID- 30224994
TI  - Perceptions of newsworthiness are contaminated by a political usefulness bias.
AB  - Are people's perceptions of the newsworthiness of events biased by a tendency to
      rate as more important any news story that seems likely to lead others to share
      their own political attitudes? To assess this, we created six pairs of
      hypothetical news stories, each describing an event that seemed likely to
      encourage people to adopt attitudes on the opposite side of a particular
      controversial issue (e.g. affirmative action and gay marriage). In total, 569
      subjects were asked to evaluate the importance of these stories 'to the
      readership of a general-circulation newspaper', disregarding how interesting they
      happened to find the event. Subjects later indicated their own personal attitudes
      to the underlying political issues. Predicted crossover interactions were
      confirmed for all six issues. All the interactions took the form of subjects
      rating stories offering 'ammunition' for their own side of the controversial
      issue as possessing greater intrinsic news importance.

PMID- 30224995
TI  - Generalized Erdos numbers for network analysis.
AB  - The identification of relationships in complex networks is critical in a variety
      of scientific contexts. This includes the identification of globally central
      nodes and analysing the importance of pairwise relationships between nodes. In
      this paper, we consider the concept of topological proximity (or 'closeness')
      between nodes in a weighted network using the generalized Erdos numbers (GENs).
      This measure satisfies a number of desirable properties for networks with nodes
      that share a finite resource. These include: (i) real-valuedness, (ii) non
      locality and (iii) asymmetry. We show that they can be used to define a
      personalized measure of the importance of nodes in a network with a natural
      interpretation that leads to new methods to measure centrality. We show that the
      square of the leading eigenvector of an importance matrix defined using the GENs
      is strongly correlated with well-known measures such as PageRank, and define a
      personalized measure of centrality that is also well correlated with other
      existing measures. The utility of this measure of topological proximity is
      demonstrated by showing the asymmetries in both the dynamics of random walks and
      the mean infection time in epidemic spreading are better predicted by the
      topological definition of closeness provided by the GENs than they are by other
      measures.

PMID- 30224996
TI  - A method for deducing neck mobility in plesiosaurs, using the exceptionally
      preserved Nichollssaura borealis.
AB  - The elongate-necked aquatic plesiosaurs existed for 135 Myr during the Mesozoic.
      The function of this elongate neck is a point of debate. Using computed
      tomography and three-dimensional (3D) modelling, the range of motion (ROM) of the
      plesiosaur Nichollssaura borealis neck was assessed. To quantify the ROM, the
      intervertebral mobility was measured along the cervical vertebral column. This
      was done by manipulating the 3D models in the lateral and dorsoventral directions
      during two trials. The first assessed the mean intervertebral ROM between pairs
      of cervical vertebrae along the entire column, and the second assessed ROM with
      reduced intervertebral spaces. The results suggest that there may be preference
      for lateral neck movements in N. borealis, which could correspond to an
      ecological function related to prey capture. This study demonstrates that 3D
      modelling is an effective tool for assessing function morphology for structures
      where no good modern analogue exists.

PMID- 30224997
TI  - Effects of sodium roasting on the leaching rate of boron-bearing tailings and its
      mechanism analysis.
AB  - The study reported was intended to improve the leaching rate of boron-bearing
      tailings, using a method of sodium roasting that uses boron-bearing tailings as
      the raw material and Na2CO3 as the sodium agent. The effects of the roasting
      temperature and Na2CO3 amount on the leaching rate of boron-bearing tailings are
      mainly evaluated. The morphology and composition of the samples after sodium
      roasting are analysed by scanning electron microscopy and X-ray diffraction. The
      results show that sodium roasting can significantly improve the leaching rate of
      boron-bearing tailings. Under the optimal conditions where roasting temperature
      is 950 degrees C, Na2CO3 amount is five times the theoretical amount and roasting
      time is 2 h, the leaching rate of boron-bearing tailings is up to 86.78%. Based
      on the analysis of the characterization results and the mechanism analysis of the
      sodium roasting process, the main reason for the increase of leaching rate is the
      reaction between Na2O produced by the decomposition of Na2CO3 and the boron in
      boron-bearing tailings resulting in soluble sodium borate. The results provide a
      scientific basis for the efficient comprehensive use of boron-bearing tailings.

PMID- 30224998
TI  - Characteristics of biochar pellets from corn straw under different pyrolysis
      temperatures.
AB  - Biomass resources have the potential to produce clean-energy. However, their
      physico-chemical properties are inferior to those of coal, and thus, biomass
      resources are not regarded as ideal feedstock for industrial application. In the
      present study, the pyrolysis of corn (maize) straw pellets was performed under
      different temperatures (400, 450, 500, 550 and 600 degrees C) at a 10 degrees C
      min-1 heating rate and 30 min residence time, and the characteristics of biochar
      pellets were carefully investigated, particularly their elemental composition,
      hydrophobicity and mechanical resistance. Fourier transform infrared, proximate
      analysis and scanning electron microscopy were performed. Results indicated that
      the mass and energy yields of the biochar pellets decreased from 35.46 to 28.65%
      and from 50.17 to 45.52%, respectively, at increased temperature. Meanwhile, the
      higher heating value of the biochar pellets increased from 15.45 MJ kg-1 in the
      raw materials to 21.86 and 24.55 MJ kg-1 in the biochar produced at 400 and 600
      degrees C, respectively. In addition, biochar pellets showed good hydrophobicity,
      which benefited their storage and transportation, though mechanical resistance
      decreased. The pellets had compact structures, regular shapes and weakened or no
      functional groups in contrast with raw pellets, and these properties played
      important roles in the improvements.

PMID- 30224999
TI  - The SNARC effect is associated with worse mathematical intelligence and poorer
      time estimation.
AB  - Interactions between the ways we process space, numbers and time may arise from
      shared and innate generic magnitude representations. Alternatively or
      concurrently, such interactions could be due to the use of physical magnitudes,
      like spatial extent, as metaphors for more abstract ones, like number and
      duration. That numbers might be spatially represented along a mental number line
      is suggested by the SNARC effect: faster left-side responses to small single
      digits, like 1 or 2, and faster right-side responses to large ones, like 8 or 9.
      Previously, we found that time estimation predicts mathematical intelligence and
      speculated that it may predict spatial ability too. Here, addressing this issue,
      we test-on a relatively large sample of adults and entirely within subjects-the
      relationships between (a) time: proficiency at producing and evaluating durations
      shorter than one second, (b) space: the ability to mentally rotate objects, (c)
      numbers: mathematical reasoning skills, and (d) space-number associations: the
      SNARC effect. Better time estimation was linked to greater mathematical
      intelligence and better spatial skills. Strikingly, however, stronger
      associations between space and numbers predicted worse mathematical intelligence
      and poorer time estimation.

PMID- 30225000
TI  - Loss of miR-143 and miR-145 in condyloma acuminatum promotes cellular
      proliferation and inhibits apoptosis by targeting NRAS.
AB  - The expression profile of miRNAs and their function in condyloma acuminatum (CA)
      remains unknown. In this study, we aimed to detect the effects of miR-143 and miR
      145, the most downregulated in CA samples using high-throughput sequencing, on
      cell proliferation and apoptosis, to determine a novel therapeutic target for CA
      recurrence. RT-qPCR was used to validate the lower expression of miR-143 and miR
      145 in a larger size of CA samples, and the expression of NRAS in CA samples was
      significantly higher than self-controls as determined by western blotting assay.
      Luciferase assay was performed to confirm that miR-143 or miR-145 targeted NRAS
      directly. Transduction of LV-pre-miR-143 or LV-pre-miR-145 to human papilloma
      virus (HPV)-infected SiHa cells led to reduced proliferation, greater apoptosis
      and inhibition of expression of NRAS, PI3 K p110alpha and p-AKT. However,
      knockout of miR-143 or miR-145 in human epidermal keratinocytes by delivery of
      CRISPR/CAS9-gRNA for target miRNAs protected cells from apoptosis and upregulated
      expression of target genes as described above. MiR-143 and miR-145 sensitized
      cells to nutlin-3a, a p53 activator and MDM2 antagonist, while their loss
      protected cells from the stress of nutlin-3a. Furthermore, siRNA targeting NRAS
      showed similar effects on proliferation and apoptosis as miR-143 or miR-145.
      Taken together, our results suggest that loss of miR-143 or miR-145 in CA
      protects HPV-infected cells from apoptosis induced by environmental stress, in
      addition to promoting cellular proliferation and inhibiting apoptosis by
      targeting NRAS/PI3 K/ATK. Restoration of miR-143 or miR-145 might provide an
      applicable and novel approach to block the recurrence and progression of CA.

PMID- 30225001
TI  - Compressor map regression modelling based on partial least squares.
AB  - In this work, two kinds of partial least squares modelling methods are applied to
      predict a compressor map: one uses a power function polynomial as the basis
      function (PLSO), and the other uses a trigonometric function polynomial (PLSN).
      To demonstrate the potential capabilities of PLSO and PLSN for a typical
      interpolated prediction and an extrapolated prediction, they are compared with
      two other classical data-driven modelling methods, namely the look-up table and
      artificial neural network (ANN). PLSO and PLSN are also compared with each other.
      The results show that PLSO and PLSN have a better prediction performance than the
      look-up table and the ANN, especially for the extrapolated prediction. The
      computational time is also decreased sharply. Compared with PLSO, PLSN is
      characterized by a higher prediction accuracy and shorter computational time than
      PLSO. It is expected that PLSN could save computational time and also improve the
      accuracy of a thermodynamic model of a diesel engine.

PMID- 30225002
TI  - Factors affecting N-nitrosodimethylamine formation from poly(diallyldimethyl
      ammonium chloride) degradation during chloramination.
AB  - Poly(diallyldimethylammonium chloride) (polyDADMAC) has been shown to be an
      important precursor of the probable human carcinogen N-nitrosodimethylamine
      (NDMA) when in contact with chloramine. In this study, we conducted an orthogonal
      experiment design to evaluate the effects of pH values, ammonia, bromide, natural
      organic matter (NOM) and monochloramine dosages on the formation of NDMA from
      polyDADMAC during chloramination. Meanwhile, single-factor experiments of pH,
      bromide and NOM prove the results of orthogonal experiment. The results supported
      that pH was the most critical factor affecting NDMA formation from polyDADMAC
      during chloramination, and the highest NDMA formation from polyDADMAC occurred at
      pH near 7 due to released DMA from polyDADMAC degradation and the critical
      importance of low concentrations of dichloramine in water. In the presence of
      excess bromide, the NDMA formation was enhanced significantly at all different pH
      values owing to bromochloramine, which has higher electronegativity of the
      brominated nitrogen atom than monochloramine or dichloramine. The NDMA formation
      from polyDADMAC in the presence of NOM was 41.7% lower than NDMA formation in the
      absence of NOM. The overwhelming majority of NDMA formation from polyDADMAC under
      simulated conditions was lower than the current advisory levels (i.e. 9 ng l-1 in
      Ontario, 10 ng l-1 in California).

PMID- 30225004
TI  - Scalable funding of Bitcoin micropayment channel networks.
AB  - The Bitcoin network has scalability problems. To increase its transaction rate
      and speed, micropayment channel networks have been proposed; however, these
      require to lock funds into specific channels. Moreover, the available space in
      the blockchain does not allow scaling to a worldwide payment system. We propose a
      new layer that sits in between the blockchain and the payment channels. The new
      layer addresses the scalability problem by enabling trustless off-blockchain
      channel funding. It consists of shared accounts of groups of nodes that flexibly
      create one-to-one channels for the payment network. The new system allows rapid
      changes of the allocation of funds to channels and reduces the cost of opening
      new channels. Instead of one blockchain transaction per channel, each user only
      needs one transaction to enter a group of nodes-within the group the user can
      create arbitrarily many channels. For a group of 20 users with 100 intra-group
      channels, the cost of the blockchain transactions is reduced by 90% compared to
      100 regular micropayment channels opened on the blockchain. This can be increased
      further to 96% if Bitcoin introduces Schnorr signatures with signature
      aggregation.

PMID- 30225003
TI  - Assessment of tea garden soils at An'xi County in southeast China reveals a mild
      threat from contamination of potentially harmful elements.
AB  - An extensive study of the spatial distribution characteristics of potentially
      harmful elements (PHEs) in tea (Camellia sinensis (L.) O. Kuntze) garden soils
      and ecological risk assessment at An'xi County, the birthplace of oolong tea in
      China, was implemented. A total of 78 soil samples were examined to determine the
      concentration of five PHEs (As, Cd, Cr, Hg and Pb), soil organic matter and pH by
      using geostatistical approaches combined with geographical information system
      analysis. All PHEs presented in the study area were slightly higher than their
      background values for provincial and national standards except Cr. Moreover,
      ecological risk assessment of PHEs in the tea garden soils at An'xi County was
      performed by means of the Hakanson method. The average ecological potential risk
      index (Er) of the five PHEs followed a descending order of Cd > Hg > Pb > As >
      Cr, and suggested a moderate ecological risk in the study area.

PMID- 30225005
TI  - Designing efficient hybrid strategies for information spreading in scale-free
      networks.
AB  - Designing a spreading strategy is one of the critical issues strongly affecting
      spreading efficiency in complex networks. In this paper, to improve the
      efficiency of information spreading in scale-free networks, we propose four
      hybrid strategies by combining two basic strategies, i.e. (i) the LS (in which
      information is preferentially spread from the large-degree vertices to the small
      degree ones), and (ii) the SL (in which information is preferentially spread from
      the small-degree vertices to the large-degree ones). The objective in combining
      the two basic LS and SL strategies is to fully exploit the advantages of both
      strategies. To evaluate the spreading efficiency of the proposed four hybrid
      strategies, we first propose an information spreading model. Then, we introduce
      the details of the proposed hybrid strategies that are formulated by combining LS
      and SL. Third, we build a set of scale-free network structures by differently
      configuring the relevant parameters. In addition, finally, we conduct various
      Monte Carlo experiments to examine the spreading efficiency of the proposed
      hybrid strategies in different scale-free network structures. Experimental
      results indicate that the proposed hybrid strategies are effective and efficient
      for spreading information in scale-free networks.

PMID- 30225006
TI  - 5'-(CGA) n sequence-assisted pH-controlled assembly of supramolecular DNA
      nanostructure.
AB  - Herein, the DNA strands containing 5'-(CGA) n and consecutive guanines are used
      to construct supramolecular DNA nanostructures that are size-controlled by pH
      values. Additionally, the introduction of thymine linkers within DNA
      nanostructures is necessary to maintain the stability of long-sized
      nanostructures. This work also demonstrates a method for accurately building DNA
      nanostructures.

PMID- 30225007
TI  - Two types of social grooming methods depending on the trade-off between the
      number and strength of social relationships.
AB  - Humans use various social bonding methods known as social grooming, e.g. face to
      face communication, greetings, phone and social networking sites (SNS). SNS have
      drastically decreased time and distance constraints of social grooming. In this
      paper, I show that two types of social grooming (elaborate social grooming and
      lightweight social grooming) were discovered in a model constructed by 13
      communication datasets including face to face, SNS and Chacma baboons. The
      separation of social grooming methods is caused by a difference in the trade-off
      between the number and strength of social relationships. The trade-off of
      elaborate social grooming is weaker than the trade-off of lightweight social
      grooming. On the other hand, the time and effort of elaborate methods are higher
      than those of lightweight methods. Additionally, my model connects social
      grooming behaviour and social relationship forms with these trade-offs. By
      analysing the model, I show that individuals tend to use elaborate social
      grooming to reinforce a few close relationships (e.g. face to face and Chacma
      baboons). By contrast, people tend to use lightweight social grooming to maintain
      many weak relationships (e.g. SNS). Humans with lightweight methods who live in
      significantly complex societies use various types of social grooming to
      effectively construct social relationships.

PMID- 30225008
TI  - Inhibition mechanism of Ca2+, Mg2+ and Fe3+ in fine cassiterite flotation using
      octanohydroxamic acid.
AB  - The existence of metal ions should not be ignored in both hydrometallurgy and
      flotation. In this study, the effects of Ca2+, Mg2+ and Fe3+ on the flotation
      performance of cassiterite using octanohydroxamic acid (OHA) as the collector
      were investigated by micro-flotation tests, X-ray photoelectron spectroscopy
      (XPS), Fourier transform infrared (FTIR) spectroscopy, contact angle, zeta (zeta)
      potential measurements and atomic force microscopy (AFM) imaging. The results of
      the flotation and contact angle experiments showed that the addition of Ca2+,
      Mg2+ and Fe3+ significantly decreased both the recovery and contact angle of
      cassiterite with pH ranged from 6.0 to 12.0 in the presence of OHA collector.
      zeta-Potential measurements, solution chemistry analysis and FTIR measurements
      indicated that the flotation recovery of the cassiterite declined due to the
      CaOH+, MgOH+ and Fe(OH)3 sites on the cassiterite surface. XPS results indicated
      that the chemisorption of OHA and calcium ions on the cassiterite surface finally
      changed its chemical properties. The AFM images also revealed that new species
      Fe(OH)3 of Fe3+ formed and adsorbed on the cassiterite surface at pH 9.0. The
      adsorption of Fe(OH)3 reduced the adsorption of OHA on the cassiterite surface,
      thus the hydrophobicity of cassiterite was deteriorated.

PMID- 30225009
TI  - Decorating gold nanostars with multiwalled carbon nanotubes for photothermal
      therapy.
AB  - Gold nanoparticles and carbon nanotubes have attracted substantial attention in
      recent years for their potential applications in photothermal therapy (PTT) as an
      emerging breakthrough in cancer treatment. Herein, a hybrid nanomaterial of gold
      nanostars/multiwalled carbon nanotubes (MWCNTs) was synthesized by two-step
      reduction via the control of several synthetic conditions such as the reducing
      agent, pH value, concentration and ratio of reagents. The material shows good
      biocompatibility and high photothermal conversion efficiency, demonstrating its
      applicability in PTT. The lack of surfactant in the synthesis process made the
      hybrid nanomaterial cell-friendly, with no effects on viability in vitro. The
      MWCNT/gold nanostars hybrid nanomaterial presented 12.4% higher photothermal
      efficiency than gold nanostars alone and showed a 2.4-fold increase over gold
      nanospheres based on a heating test under 808 nm laser irradiation. Moreover, the
      MWCNTs/gold nanostars at low concentration (0.32 nM) exhibited remarkably
      improved photothermal cancer cell-killing efficacy, which may be attributed to
      the surface plasmon resonance absorption of the gold nanostars and the combined
      effects of enhanced coupling between the MWCNTs and gold nanostars. Collectively,
      these results demonstrate that the MWCNTs/gold nanostars developed herein show
      prominent photothermal value, and thus may serve as a novel photothermal agent
      for cancer therapy.

PMID- 30225010
TI  - A Brucke-Bartley effect for contrast.
AB  - Accurate derivation of the psychophysical (a.k.a. transducer) function from just
      notable differences requires accurate knowledge of the relationship between the
      mean and variance of apparent intensities. Alternatively, a psychophysical
      function can be derived from estimates of the average between easily
      discriminable intensities. Such estimates are unlikely to be biased by the
      aforementioned variance, but they are notoriously variable and may stem from
      decisional processes that are more cognitive than sensory. In this paper, to
      minimize cognitive pollution, we used amplitude-modulated contrast. As the
      spatial or temporal (carrier) frequency increased, estimates of average intensity
      became less variable across observers, converging on values that were closer to
      mean power (i.e. contrast2) than mean contrast. Simply put, apparent contrast
      increases when physical contrast flickers. This result is analogous to Brucke's
      finding that brightness increases when luminance flickers. It implies an
      expansive transduction of contrast in the same way that Brucke's finding implies
      an expansive transduction of luminance.

PMID- 30225011
TI  - Improved mould resistance and antibacterial activity of bamboo coated with
      ZnO/graphene.
AB  - Bamboo is susceptible to mould and attack by fungi because of its high content of
      starch and sugar. To make bamboo-based outdoor materials, a new type of bamboo
      timber with improved mould resistance and antibacterial activity, coated with
      reduced graphene oxide and nanocrystal ZnO (abbreviated as RGO@ZnOBT), was
      fabricated by a two-step dip-dry and hydrothermal process. A possible synthesis
      mechanism for RGO@ZnOBT was investigated by X-ray diffraction, scanning electron
      microscopy, transmission electron microscope, energy-dispersal X-ray analysis, X
      ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy.
      According to the China standard test method, the Aspergillus niger mould
      resistance of RGO@ZnOBT is grade 2, whereas the Trichoderma viride and
      Penicillium citrinum mould resistance of RGO@ZnOBT is grade 0, both of which are
      better than the grade 4 of original bamboo timber. The Escherichia coli
      resistance test showed that the antibacterial circle of RGO@ZnOBT is 3 mm, which
      is significantly higher than that of original bamboo timber (0 mm). The
      antibacterial activity of treated bamboo is significantly improved compared with
      that of untreated bamboo.

PMID- 30225012
TI  - NiS submicron cubes with efficient electrocatalytic activity as the counter
      electrode of dye-sensitized solar cells.
AB  - In this work, nickel sulfide (NiS) submicron cubes, synthesized by an easy
      hydrothermal method, were investigated as an efficient electrocatalytic material
      of dye-sensitized solar cells (DSSCs), to our knowledge, for the first time. Part
      of the NiS submicron cubes were grown together in a hydrothermal procedure and
      formed the connected submicron cube cluster. The NiS submicron cubes (with a
      diameter of 300-800 nm) showed excellent electrocatalytic activity and presented
      superior photovoltaic performance when it was used as an electrocatalytic
      material for the counter electrode (CE) of DSSCs. The CE composed of the NiS
      submicron cubes could achieve a photovoltaic efficiency of 6.4%, showing their
      superior performance compared with the typical Pt electrode (which with the
      corresponding conversion efficiency was 5.3% at the same condition). The low-cost
      NiS submicron cube electrode could be a competitive candidate to replace the
      traditional Pt electrode in DSSCs. The simple composition procedure of NiS
      submicron cubes could enable the low-cost mass production of an efficient NiS
      submicron cube electrode to be easily accomplished.

PMID- 30225013
TI  - Context-dependent variability in blue whale acoustic behaviour.
AB  - Acoustic communication is an important aspect of reproductive, foraging and
      social behaviours for many marine species. Northeast Pacific blue whales
      (Balaenoptera musculus) produce three different call types-A, B and D calls. All
      may be produced as singular calls, but A and B calls also occur in phrases to
      form songs. To evaluate the behavioural context of singular call and phrase
      production in blue whales, the acoustic and dive profile data from tags deployed
      on individuals off southern California were assessed using generalized estimating
      equations. Only 22% of all deployments contained sounds attributed to the tagged
      animal. A larger proportion of tagged animals were female (47%) than male (13%),
      with 40% of unknown sex. Fifty per cent of tags deployed on males contained
      sounds attributed to the tagged whale, while only a few (5%) deployed on females
      did. Most calls were produced at shallow depths (less than 30 m). Repetitive
      phrasing (singing) and production of singular calls were most common during
      shallow, non-lunging dives, with the latter also common during surface behaviour.
      Higher sound production rates occurred during autumn than summer and they varied
      with time-of-day: singular call rates were higher at dawn and dusk, while phrase
      production rates were highest at dusk and night.

PMID- 30225014
TI  - Flight behaviour of malaria mosquitoes around odour-baited traps: capture and
      escape dynamics.
AB  - Host-seeking mosquitoes rely on a range of sensory cues to find and approach
      blood hosts, as well as to avoid host detection. By using odour blends and visual
      cues that attract anthropophilic mosquitoes, odour-baited traps have been
      developed to monitor and control human pathogen-transmitting vectors. Although
      long-range attraction of such traps has already been studied thoroughly, close
      range response of mosquitoes to these traps has been largely ignored. Here, we
      studied the flight behaviour of female malaria mosquitoes (Anopheles coluzzii) in
      the immediate vicinity of a commercially available odour-baited trap, positioned
      in a hanging and standing orientation. By analysing more than 2500 three
      dimensional flight tracks, we elucidated how mosquitoes reacted to the trap, and
      how this led to capture. The measured flight dynamics revealed two distinct
      stereotypical behaviours: (i) mosquitoes that approached a trap tended to
      simultaneously fly downward towards the ground; (ii) mosquitoes that came close
      to a trap changed their flight direction by rapidly accelerating upward. The
      combination of these behaviours led to strikingly different flight patterns and
      capture dynamics, resulting in contrasting short-range attractiveness and capture
      mechanism of the oppositely oriented traps. These new insights may help in
      improving odour-baited traps, and consequently their contribution in global
      vector control strategies.

PMID- 30225016
TI  - Geomorphological evidence of large vertebrates interacting with the seafloor at
      abyssal depths in a region designated for deep-sea mining.
AB  - Exploration licences for seafloor mineral deposits have been granted across large
      areas of the world's oceans, with the abyssal Pacific Ocean being the primary
      target for polymetallic nodules-a potentially valuable source of minerals. These
      nodule-bearing areas support a large diversity of deep-sea life and although
      studies have begun to characterize the benthic fauna within the region, the
      ecological interactions between large bathypelagic vertebrates of the open ocean
      and the abyssal seafloor remain largely unknown. Here we report seafloor
      geomorphological alterations observed by an autonomous underwater vehicle that
      suggest large vertebrates could have interacted with the seafloor to a maximum
      depth of 4258 m in the recent geological past. Patterns of disturbance on the
      seafloor are broadly comparable to those recorded in other regions of the world's
      oceans attributed to beaked whales. These observations have important
      implications for baseline ecological assessments and the environmental management
      of potential future mining activities within this region of the Pacific.

PMID- 30225015
TI  - How wide is the cone of direct gaze?
AB  - The cone of direct gaze refers to the range of gaze deviations an observer
      accepts as looking directly at them. Previous experiments have calculated the
      width of the cone of direct gaze using the gaze deviations actually presented to
      the observer, however, there is considerable evidence that observers actually
      perceive gaze to be systematically more deviated than actually presented. Here,
      we examine the width of the cone of direct gaze in units of perceived gaze
      deviation. In doing so, we are able to disambiguate differences in width both
      within and between observers that are due to differences in their perception of
      gaze and due to differences in what observers consider to be looking at them. We
      suggest that this line of inquiry can offer further insight into the perception
      of gaze direction, and how this perception may differ in clinical populations.

PMID- 30225017
TI  - Towards open data blockchain analytics: a Bitcoin perspective.
AB  - Bitcoin is the first implementation of a technology that has become known as a
      'public permissionless' blockchain. Such systems allow public read/write access
      to an append-only blockchain database without the need for any mediating central
      authority. Instead, they guarantee access, security and protocol conformity
      through an elegant combination of cryptographic assurances and game theoretic
      economic incentives. Not until the advent of the Bitcoin blockchain has such a
      trusted, transparent, comprehensive and granular dataset of digital economic
      behaviours been available for public network analysis. In this article, by
      translating the cumbersome binary data structure of the Bitcoin blockchain into a
      high fidelity graph model, we demonstrate through various analyses the often
      overlooked social and econometric benefits of employing such a novel open data
      architecture. Specifically, we show: (i) how repeated patterns of transaction
      behaviours can be revealed to link user activity across the blockchain; (ii) how
      newly mined bitcoin can be associated to demonstrate individual accumulations of
      wealth; (iii) through application of the naive quantity theory of money that
      Bitcoin's disinflationary properties can be revealed and measured; and (iv) how
      the user community can develop coordinated defences against repeated denial of
      service attacks on the network. Such public analyses of this open data are
      exemplary benefits unavailable to the closed data models of the 'private
      permissioned' distributed ledger architectures currently dominating enterprise
      level blockchain development owing to existing issues of scalability,
      confidentiality and governance.

PMID- 30225018
TI  - Waterborne polyurethane as a carbon coating for micrometre-sized silicon-based
      lithium-ion battery anode material.
AB  - Waterborne polyurethane (WPU) is first used as a carbon-coating source for
      micrometre-sized silicon. The remaining nitrogen (N) and oxygen (O) heteroatoms
      during pyrolysis of the WPU interact with the surface oxide on the silicon (Si)
      particles via hydrogen bonding (Si-OH?N and Si-OH?O). The N and O atoms involved
      in the carbon network can interact with the lithium ions, which is conducive to
      lithium-ion insertion. A satisfactory performance of the Si@N, O-doped carbon
      (Si@CNO) anode is gained at 25 and 55 degrees C. The Si@CNO anode shows stable
      cycling performance (capacity retention of 70.0% over 100 cycles at 25 degrees C
      and 60.3% over 90 cycles at 55 degrees C with a current density of 500 mA g-1)
      and a superior rate capacity of 864.1 mA h g-1 at 1000 mA g-1 (25 degrees C). The
      improved electrochemical performance of the Si@CNO electrode is attributed to the
      enhanced electrical conductivity and structural stability.

PMID- 30225019
TI  - Resistance is futile: lack of predator switching and a preference for native prey
      predict the success of an invasive prey species.
AB  - Invasive species continue to severely impact biodiversity, yet predicting the
      success or failure of introduced species has remained elusive. In particular, the
      relationship between community invasibility and native species diversity remains
      obscure. Here, we apply two traditional ecological concepts that inform prey
      population stability and hence invasibility. We first show that the native
      predatory crustacean Gammarus duebeni celticus exhibited similar type II
      (destabilizing) functional responses (FRs) towards native mayfly prey and
      invasive amphipod prey, when these prey species were presented separately.
      However, when the two prey species were presented simultaneously, the predator
      did not exhibit prey switching, instead consuming disproportionately more native
      prey than expected from the relative abundance of native and invasive species.
      These consumptive propensities foster reductions of native prey, while
      simultaneously limiting biotic resistance against the invasive species by the
      native predator. Since our theoretical considerations and laboratory results
      match known field invasion patterns, we advocate the increased consideration of
      FR and prey switching studies to understand and predict the success of invasive
      species.

PMID- 30225020
TI  - Advancing risk assessment: mechanistic dose-response modelling of Listeria
      monocytogenes infection in human populations.
AB  - The utility of characterizing the effects of strain variation and
      individual/subgroup susceptibility on dose-response outcomes has motivated the
      search for new approaches beyond the popular use of the exponential dose-response
      model for listeriosis. While descriptive models can account for such variation,
      they have limited power to extrapolate beyond the details of particular
      outbreaks. By contrast, this study exhibits dose-response relationships from a
      mechanistic basis, quantifying key biological factors involved in pathogen-host
      dynamics. An efficient computational algorithm and geometric interpretation of
      the infection pathway are developed to connect dose-response relationships with
      the underlying bistable dynamics of the model. Relying on in vitro experiments as
      well as outbreak data, we estimate plausible parameters for the human context.
      Despite the presence of uncertainty in such parameters, sensitivity analysis
      reveals that the host response is most influenced by the pathogen-immune system
      interaction. In particular, we show how variation in this interaction across a
      subgroup of the population dictates the shape of dose-response curves. Finally,
      in terms of future experimentation, our model results provide guidelines and
      highlight vital aspects of the interplay between immune cells and particular
      strains of Listeria monocytogenes that should be examined.

PMID- 30225021
TI  - Revisiting behaviour of monometallic catalysts in chemical vapour deposition
      synthesis of single-walled carbon nanotubes.
AB  - A catalyst is essential for the controlled synthesis of single-walled carbon
      nanotubes (SWNTs) by chemical vapour deposition (CVD). However, it is difficult
      to observe these nanosized particles in their original forms and in a statistical
      manner, which has resulted in a vague understanding of the behaviours of these
      particles. We present a technique to solve this long-standing issue. The key is
      to have an MEMS fabricated suspended SiO2 layer, which is thick enough to support
      catalyst deposition and nanotube growth but thin enough to allow electron beams
      to transit. On a 20 nm SiO2 film, we confirm that catalyst can be observed at an
      atomic resolution, and the catalyst-SWNT junctions can also be routinely
      observed. As a demonstration of this technique, we revisited the behaviour of
      monometallic catalysts through a systematic investigation of the size, chemical
      state and crystal structure of particles before and after high-temperature CVD.
      The active catalyst is found to follow a tangential growth mode, while the
      inactive catalyst is divided into three mechanisms: size growth, metal loss and
      inappropriate precipitation. The latter two mechanisms were not possible to
      observe by previous techniques.

PMID- 30225022
TI  - Vertical stress and stability of interburden over an abandoned pillar working
      before upward mining: a case study.
AB  - Upward mining of the residual coal seam over an abandoned pillar working is one
      of the effective measures to alleviate the contradiction between limited
      resources and increased consumption. Interburden stability over an abandoned
      pillar working plays a significant role in guaranteeing the safety of upward
      mining; however, it has not yet been extensively studied and understood. In this
      study, the vertical stress of the interburden over an abandoned pillar working
      was first investigated. The mechanical model of the interburden was established
      and the damage conditions were analysed. Then, the stability of the interburden
      over 38502 abandoned workings in Baijiazhuang coal mine was determined by
      mechanical analysis and field monitoring. The results show that: (i) Vertical
      stress of the interburden over abandoned mining zones is clearly lower than the
      initial stress, indicating the existence of a de-stressed effect. Moreover,
      vertical stress of the interburden over residual coal pillars is greater than the
      initial stress, which is the evidence of a stress concentration effect. (ii) The
      interburden over an abandoned pillar working should be regarded as an elastic
      rectangular plate supported by generalized Kelvin bodies in mechanical modelling.
      (iii) The interburden over abandoned mining zones may experience two damage
      stages. In the first stage, initial plastic damage appears at the central region
      of interburden. In the second stage, the plastic damage evolves from the central
      point to the surrounding areas. (iv) The mechanical analysis and field monitoring
      both indicate the initial damage occurred at the central region over 38502
      abandoned workings in Baijiazhuang coal mine before upward mining. Related rock
      control measures should be implemented in that region to guarantee the safe
      mining of the residual coal seam.

PMID- 30225023
TI  - Electrokinetic remediation of heavy metals from municipal solid waste
      incineration fly ash pretreated by nitric acid.
AB  - Municipal solid waste incineration (MSWI) fly ash has a high concentration of
      heavy metals (HMs) which are hazardous to the environment. Moreover, it has high
      pH and buffering capacity which hinders the removal of HMs. Another constraining
      factor is the considerable fraction of HMs which exist in oxidizable and
      reducible states. The acid pretreatment of MSWI fly ash is a key solution to this
      problem. Therefore, the current experiment is carried out to evaluate the effect
      of acid pretreatment of MSWI fly ash and reaction/proposed time on the removal
      efficiency of HMs through an electrokinetic experiment. The leaching experiment
      results show that acid pretreatment has increased the desorption/release of heavy
      metal ions (Pb2+, Cd2+, Cu2+ and Zn2+). It enhances the migration of HM ions in
      electrolytic cells which get precipitated at the cathode, thereby increasing the
      removal efficiency of HMs in the electrokinetic experiment. Moreover, it is found
      that prolonged proposed time (12 d) has significant effect on the removal
      efficiency of HMs. Finally, it is concluded that acid pretreatment and prolonged
      proposed time have enhanced the removal electrokinetic remediation of HMs which
      is carried out via three processes, i.e. desorption (enhanced by acidification),
      migration and precipitation.

PMID- 30225024
TI  - Scalable population-level modelling of biological cells incorporating mechanics
      and kinetics in continuous time.
AB  - The processes taking place inside the living cell are now understood to the point
      where predictive computational models can be used to gain detailed understanding
      of important biological phenomena. A key challenge is to extrapolate this
      detailed knowledge of the individual cell to be able to explain at the population
      level how cells interact and respond with each other and their environment. In
      particular, the goal is to understand how organisms develop, maintain and repair
      functional tissues and organs. In this paper, we propose a novel computational
      framework for modelling populations of interacting cells. Our framework
      incorporates mechanistic, constitutive descriptions of biomechanical properties
      of the cell population, and uses a coarse-graining approach to derive individual
      rate laws that enable propagation of the population through time. Thanks to its
      multiscale nature, the resulting simulation algorithm is extremely scalable and
      highly efficient. As highlighted in our computational examples, the framework is
      also very flexible and may straightforwardly be coupled with continuous-time
      descriptions of biochemical signalling within, and between, individual cells.

PMID- 30225025
TI  - The impact of experimental design choices on parameter inference for models of
      growing cell colonies.
AB  - To better understand development, repair and disease progression, it is useful to
      quantify the behaviour of proliferative and motile cell populations as they grow
      and expand to fill their local environment. Inferring parameters associated with
      mechanistic models of cell colony growth using quantitative data collected from
      carefully designed experiments provides a natural means to elucidate the relative
      contributions of various processes to the growth of the colony. In this work, we
      explore how experimental design impacts our ability to infer parameters for
      simple models of the growth of proliferative and motile cell populations. We
      adopt a Bayesian approach, which allows us to characterize the uncertainty
      associated with estimates of the model parameters. Our results suggest that
      experimental designs that incorporate initial spatial heterogeneities in cell
      positions facilitate parameter inference without the requirement of cell
      tracking, while designs that involve uniform initial placement of cells require
      cell tracking for accurate parameter inference. As cell tracking is an
      experimental bottleneck in many studies of this type, our recommendations for
      experimental design provide for significant potential time and cost savings in
      the analysis of cell colony growth.

PMID- 30225026
TI  - Searching for the bottom of the ego well: failure to uncover ego depletion in
      Many Labs 3.
AB  - According to a popular model of self-control, willpower depends on a limited
      resource that can be depleted when we perform a task demanding self-control. This
      theory has been put to the test in hundreds of experiments showing that
      completing a task that demands high self-control usually hinders performance in
      any secondary task that subsequently taxes self-control. Over the last 5 years,
      the reliability of the empirical evidence supporting this model has been
      questioned. In the present study, we reanalysed data from a large-scale study
      Many Labs 3-to test whether performing a depleting task has any effect on a
      secondary task that also relies on self-control. Although we used a large sample
      of more than 2000 participants for our analyses, we did not find any significant
      evidence of ego depletion: persistence on an anagram-solving task (a typical
      measure of self-control) was not affected by previous completion of a Stroop task
      (a typical depleting task in this literature). Our results suggest that either
      ego depletion is not a real effect or, alternatively, persistence in anagram
      solving may not be an optimal measure to test it.

PMID- 30225027
TI  - Mine safety assessment based on basic event importance: grey relational analysis
      and bow tie model.
AB  - Safety assessments are a crucial first step in preventing coal and gas outburst
      accidents. The main purpose of this study was to create a new accident prevention
      technique using a novel safety assessment method based on fault tree basic event
      importance, grey relational analysis and the bow tie model. The innovation of the
      proposed method lies in generating the composite importance of a basic event from
      the fundamental importance via grey relational analysis; bow tie analysis serves
      to reveal the most critical basic event. First, the minimal cut sets and minimal
      path sets of a coal and gas outburst accident are determined by fault tree
      analysis. The role of minimal cut and path sets is determined and the coal and
      gas outburst occurrence frequency is calculated accordingly. Second, the
      structure, probability, critical and Fussell-Vesely importance ranked basic
      events differently due to different aspects of the basic events as investigated.
      We establish a composite importance to represent single basic events and achieved
      new ranking results by grey relational analysis. Third, the critical basic event
      low permeability coefficient is analysed via bow tie model and safety measures
      are defined which prevent the dangerous consequences of a low permeability
      coefficient. An actual coal and gas outburst accident is used as a case study to
      test the feasibility and effectiveness of the proposed method.

PMID- 30225029
TI  - Proof of Kernel Work: a democratic low-energy consensus for distributed access
      control protocols.
AB  - We adjust the Proof of Work (PoW) consensus mechanism used in Bitcoin and
      Ethereum so that we can build on its strength while also addressing, in part,
      some of its perceived weaknesses. Notably, our work is motivated by the high
      energy consumption for mining PoW, and we want to restrict the use of PoW to a
      configurable, expected size of nodes, as a function of the local blockchain
      state. The approach we develop for this rests on three pillars: (i) Proof of
      Kernel Work (PoKW), a means of dynamically reducing the set of nodes that can
      participate in the solving of PoW puzzles such that an adversary cannot increase
      his attack surface because of such a reduction; (ii) Practical Adaptation of
      Existing Technology, a realization of this PoW reduction through an adaptation of
      existing blockchain and enterprise technology stacks; and (iii) Machine Learning
      for Adaptive System Resiliency, the use of techniques from artificial
      intelligence to make our approach adaptive to system, network and attack
      dynamics. We develop here, in detail, the first pillar and illustrate the second
      pillar through a real use case, a pilot project done with Porsche on controlling
      permissions to vehicle and data log accesses. We also discuss pertinent attack
      vectors for PoKW consensus and their mitigation. Moreover, we sketch how our
      approach may lead to more democratic PoKW-based blockchain systems for public
      networks that may inherit the resilience of blockchains based on PoW.

PMID- 30225028
TI  - Algorithmically probable mutations reproduce aspects of evolution, such as
      convergence rate, genetic memory and modularity.
AB  - Natural selection explains how life has evolved over millions of years from more
      primitive forms. The speed at which this happens, however, has sometimes defied
      formal explanations when based on random (uniformly distributed) mutations. Here,
      we investigate the application of a simplicity bias based on a natural but
      algorithmic distribution of mutations (no recombination) in various examples,
      particularly binary matrices, in order to compare evolutionary convergence rates.
      Results both on synthetic and on small biological examples indicate an
      accelerated rate when mutations are not statistically uniform but algorithmically
      uniform. We show that algorithmic distributions can evolve modularity and genetic
      memory by preservation of structures when they first occur sometimes leading to
      an accelerated production of diversity but also to population extinctions,
      possibly explaining naturally occurring phenomena such as diversity explosions
      (e.g. the Cambrian) and massive extinctions (e.g. the End Triassic) whose causes
      are currently a cause for debate. The natural approach introduced here appears to
      be a better approximation to biological evolution than models based exclusively
      upon random uniform mutations, and it also approaches a formal version of open
      ended evolution based on previous formal results. These results validate some
      suggestions in the direction that computation may be an equally important driver
      of evolution. We also show that inducing the method on problems of optimization,
      such as genetic algorithms, has the potential to accelerate convergence of
      artificial evolutionary algorithms.

PMID- 30225030
TI  - A dwarf walrus from the Miocene of Baja California Sur, Mexico.
AB  - Here, we describe the odobenid Nanodobenus arandai gen. et sp. nov., based on a
      nearly complete left mandible from the mid to late Miocene Tortugas Formation in
      Baja California Sur. Nanodobenus is distinguished among odobenids by displaying a
      unique combination of plesiomorphic and derived characters, such as narrow
      mandibular symphysis, well-developed genial tuberosity, bilobed canine and p2
      roots, bulbous post-canine teeth with the paraconid, protoconid and hypoconid,
      and smooth lingual cingula. Moreover, it is characterized by its small adult body
      length, which is estimated at about 1.65 m. Throughout the Miocene-Pliocene
      odobenids are characterized by an increase in body size, especially after the
      extinction of desmatophocids in the late Miocene. The small size of Nanodobenus
      departs from this trend, demonstrating that there was greater size disparity
      among odobenids in the mid-late Miocene than previously thought. It is
      hypothesized that Nanodobenus occupied a niche that was later on occupied by
      similar-sized otariids, such as Thalassoleon mexicanus, which occurs
      sympatrically with large odobenids in the overlying Almejas Formation.

PMID- 30225031
TI  - Social and endocrine correlates of immune function in meerkats: implications for
      the immunocompetence handicap hypothesis.
AB  - Social status can mediate effects on the immune system, with profound
      consequences for individual health; nevertheless, most investigators of status
      related disparities in free-ranging animals have used faecal parasite burdens to
      proxy immune function in the males of male-dominant species. We instead use
      direct measures of innate immune function (complement and natural antibodies) to
      examine status-related immunocompetence in both sexes of a female-dominant
      species. The meerkat is a unique model for such a study because it is a
      cooperatively breeding species in which status-related differences are extreme,
      evident in reproductive skew, morphology, behaviour, communication and
      physiology, including that dominant females naturally express the greatest total
      androgen (androstenedione plus testosterone) concentrations. We found that,
      relative to subordinates, dominant animals had reduced serum bacteria-killing
      abilities; also, relative to subordinate females, dominant females had reduced
      haemolytic complement activities. Irrespective of an individual's sex or social
      status, androstenedione concentrations (but not body condition, age or
      reproductive activity) negatively predicted concurrent immunocompetence. Thus,
      dominant meerkats of both sexes are immunocompromised. Moreover, in female
      meerkats, androstenedione perhaps acting directly or via local conversion, may
      exert a double-edged effect of promoting dominance and reproductive success at
      the cost of increased parasitism and reduced immune function. Given the prominent
      signalling of dominance in female meerkats, these findings may relate to the
      immunocompetence handicap hypothesis (ICHH); however, our data would suggest that
      the endocrine mechanism underlying the ICHH need not be mediated solely by
      testosterone and might explain trade-offs in females, as well as in males.

PMID- 30225032
TI  - Data availability, reusability, and analytic reproducibility: evaluating the
      impact of a mandatory open data policy at the journal Cognition.
AB  - Access to data is a critical feature of an efficient, progressive and ultimately
      self-correcting scientific ecosystem. But the extent to which in-principle
      benefits of data sharing are realized in practice is unclear. Crucially, it is
      largely unknown whether published findings can be reproduced by repeating
      reported analyses upon shared data ('analytic reproducibility'). To investigate
      this, we conducted an observational evaluation of a mandatory open data policy
      introduced at the journal Cognition. Interrupted time-series analyses indicated a
      substantial post-policy increase in data available statements (104/417, 25% pre
      policy to 136/174, 78% post-policy), although not all data appeared reusable
      (23/104, 22% pre-policy to 85/136, 62%, post-policy). For 35 of the articles
      determined to have reusable data, we attempted to reproduce 1324 target values.
      Ultimately, 64 values could not be reproduced within a 10% margin of error. For
      22 articles all target values were reproduced, but 11 of these required author
      assistance. For 13 articles at least one value could not be reproduced despite
      author assistance. Importantly, there were no clear indications that original
      conclusions were seriously impacted. Mandatory open data policies can increase
      the frequency and quality of data sharing. However, suboptimal data curation,
      unclear analysis specification and reporting errors can impede analytic
      reproducibility, undermining the utility of data sharing and the credibility of
      scientific findings.

PMID- 30225033
TI  - The shark-tuna dichotomy: why tuna lay tiny eggs but sharks produce large
      offspring.
AB  - Teleosts such as tunas and billfish lay millions of tiny eggs weighing on the
      order of 0.001 g, whereas chondrichthyes such as sharks and rays produce a few
      eggs or live offspring weighing about 2% of adult body mass, as much as 10 000 g
      in some species. Why are the strategies so extreme, and why are intermediate ones
      absent? Building on previous work, we show quantitatively how offspring size
      reflects the relationship between growth and death rates. We construct fitness
      contours as functions of offspring size and number, and show how these can be
      derived from juvenile growth and survivorship curves. Convex contours,
      corresponding to Pearl Type 1 and 2 survivorship curves, select for extremes,
      either miniscule or large offspring; concave contours select for offspring of
      intermediate size. Of particular interest are what we call critical straight-line
      fitness contours, corresponding to log-linear Pearl Type 3 survivorship curves,
      which separate regimes that select for opposite optimal offspring sizes.

PMID- 30225034
TI  - Influences of transversely isotropic rheology and translational diffusion on the
      stability of active suspensions.
AB  - Suspensions of self-motile, elongated particles are a topic of significant
      current interest, exemplifying a form of 'active matter'. Examples include self
      propelling bacteria, algae and sperm, and artificial swimmers. Ericksen's model
      of a transversely isotropic fluid (Ericksen 1960 Colloid Polym. Sci.173, 117-122
      (doi:10.1007/bf01502416)) treats suspensions of non-motile particles as a
      continuum with an evolving preferred direction; this model describes fibrous
      materials as diverse as extracellular matrix, textile tufts and plant cell walls.
      Director-dependent effects are incorporated through a modified stress tensor with
      four viscosity-like parameters. By making fundamental connections with recent
      models for active suspensions, we propose a modification to Ericksen's model,
      mainly the inclusion of self-motility; this can be considered the simplest
      description of an oriented suspension including transversely isotropic effects.
      Motivated by the fact that transversely isotropic fluids exhibit modified flow
      stability, we conduct a linear stability analysis of two distinct cases, aligned
      and isotropic suspensions of elongated active particles. Novel aspects include
      the anisotropic rheology and translational diffusion. In general, anisotropic
      effects increase the instability of small perturbations, while translational
      diffusion stabilizes a range of wave-directions and, in some cases, a finite
      range of wavenumbers, thus emphasizing that both anisotropy and translational
      diffusion can have important effects in these systems.

PMID- 30225035
TI  - tarsal-less is expressed as a gap gene but has no gap gene phenotype in the moth
      midge Clogmia albipunctata.
AB  - Gap genes are involved in segment determination during early development of the
      vinegar fly Drosophila melanogaster and other dipteran insects (flies, midges and
      mosquitoes). They are expressed in overlapping domains along the antero-posterior
      (A-P) axis of the blastoderm embryo. While gap domains cover the entire length of
      the A-P axis in Drosophila, there is a region in the blastoderm of the moth midge
      Clogmia albipunctata, which lacks canonical gap gene expression. Is a non
      canonical gap gene functioning in this area? Here, we characterize tarsal-less
      (tal) in C. albipunctata. The homologue of tal in the flour beetle Tribolium
      castaneum (called milles-pattes, mlpt) is a bona fide gap gene. We find that Ca
      tal is expressed in the region previously reported as lacking gap gene
      expression. Using RNA interference, we study the interaction of Ca-tal with gap
      genes. We show that Ca-tal is regulated by gap genes, but only has a very subtle
      effect on tailless (Ca-tll), while not affecting other gap genes at all.
      Moreover, cuticle phenotypes of Ca-tal depleted embryos do not show any gap
      phenotype. We conclude that Ca-tal is expressed and regulated like a gap gene,
      but does not function as a gap gene in C. albipunctata.

PMID- 30225036
TI  - Species' ecological functionality alters the outcome of fish stocking success
      predicted by a food-web model.
AB  - Fish stocking is used worldwide in conservation and management, but its effects
      on food-web dynamics and ecosystem stability are poorly known. To better
      understand these effects and predict the outcomes of stocking, we used an
      empirically validated network model of a well-studied lake ecosystem. We simulate
      two stocking scenarios with two native fish species valuable for fishing. In the
      first scenario, we stock planktivorous fish (whitefish) larvae in the ecosystem.
      This leads to a 1% increase in adult whitefish biomasses and decreases the
      biomasses of the top predator (perch). In the second scenario, we also stock
      perch larvae in the ecosystem. This decreases the planktivorous whitefish and the
      oldest top predator age class biomasses, and destabilizes the ecosystem. Our
      results demonstrate that the effects of stocking depend on the species' position
      in the food web and thus cannot be assessed without considering interacting
      species. We further show that stocking can lead to undesired outcomes from both
      management and conservation perspectives. The gains of stocking can remain minor
      and have adverse effects on the entire ecosystem.

PMID- 30225037
TI  - Are generalists more innovative than specialists? A comparison of innovative
      abilities in two wild sympatric mouse lemur species.
AB  - The propensity to flexibly innovate behavioural variants might advantage animals
      when dealing with novel or modified ecological or social challenges.
      Interspecific innovative abilities can be predicted by the degree of ecological
      generalism and intraspecific variation is predicted by personality traits. To
      examine the effects of these factors on innovation, we compared problem-solving
      abilities in the generalist grey mouse lemurs (Microcebus murinus) and the more
      specialized Madame Berthe's mouse lemurs (Microcebus berthae) in western
      Madagascar. We examined personality traits by testing 54 individuals in open
      field and novel object tests, and we assessed problem-solving abilities by
      presenting an artificial feeding-box that could be opened by three different
      techniques. The first two techniques presented novel problems and the third
      technique a modified problem to the more complex second novel problem. In both
      species, motivation, early success and better inhibitory control characterized
      innovators and predicted superior problem-solving performance. Although both
      species performed equally well in finding a solution to the novel problems, the
      specialist species was more efficient in finding a novel solution to a familiar
      problem. Since the ecological specialist also exhibited more inhibitory control
      in this task than the generalist, we propose that specialists may dispose of more
      efficient problem-solving behaviour.

PMID- 30225038
TI  - Goats prefer positive human emotional facial expressions.
AB  - Domestication has shaped the physiology and the behaviour of animals to better
      adapt to human environments. Therefore, human facial expressions may be highly
      informative for animals domesticated for working closely with people, such as
      dogs and horses. However, it is not known whether other animals, and particularly
      those domesticated primarily for production, such as goats, are capable of
      perceiving human emotional cues. In this study, we investigated whether goats can
      distinguish human facial expressions when simultaneously shown two images of an
      unfamiliar human with different emotional valences (positive/happy or
      negative/angry). Both images were vertically attached to a wall on one side of a
      test arena, 1.3 m apart, and goats were released from the opposite side of the
      arena (distance of 4.0 m) and were free to explore and interact with the stimuli
      during the trials. Each of four test trials lasted 30 s. Overall, we found that
      goats preferred to interact first with happy faces, meaning that they are
      sensitive to human facial emotional cues. Goats interacted first, more often and
      for longer duration with positive faces when they were positioned on the right
      side. However, no preference was found when the positive faces were placed on the
      left side. We show that animals domesticated for production can discriminate
      human facial expressions with different emotional valences and prefer to interact
      with positive ones. Therefore, the impact of domestication on animal cognitive
      abilities may be more far-reaching than previously assumed.

PMID- 30225039
TI  - Comparisons of reproductive function and fatty acid fillet quality between
      triploid and diploid farm Atlantic salmon (Salmo salar).
AB  - Triploidy could prevent escaped farm salmon breeding in the wild, while also
      improving nutrient quality within farmed fillets. Despite these potential
      advantages, triploid Atlantic salmon have not been widely used in aquaculture,
      and their reproductive function has yet to be fully evaluated. Here, we compare
      reproductive function and fillet composition between triploid and diploid farm
      salmon under standard aquaculture rearing conditions. We show that female
      triploids are sterile and do not develop gonads. By contrast, males produce large
      numbers of motile spermatozoa capable of fertilizing wild salmon eggs. However,
      compared with diploids, reproductive development and survival rates of eggs
      fertilized by triploid males were significantly reduced, with less than 1% of
      eggs sired by triploid males reaching late-eyed stages of development. Analyses
      of fillets showed that total lipid and fatty acid quantities were significantly
      lower in triploid than in diploid Atlantic salmon fillets. However, when fatty
      acids were normalized to total lipid content, triploid fillets had significantly
      higher relative levels of important omega-3 long-chain polyunsaturated fatty
      acids. Our results show that: (i) escaped triploid farm salmon are very unlikely
      to reproduce in the wild and (ii) if able to match diploid fillet lipid content,
      triploid farm salmon could achieve better fillet quality in terms of essential
      fatty acids.

PMID- 30225040
TI  - A giant dapediid from the Late Triassic of Switzerland and insights into
      neopterygian phylogeny.
AB  - A new Triassic neopterygian is described on the basis of a large three
      dimensional neurocranium from the Rhaetian (Late Triassic) of the Kossen
      Formation (Schesaplana, Grisons, Switzerland). CT scanning reveals neurocranial
      features similar to Dapedium, suggesting that this new genus, Scopulipiscis
      saxciput gen. et sp. nov., was deep-bodied and potentially durophagous, although
      no associated dental material is known. An expanded phylogenetic analysis of
      actinopterygians resolves Dapediidae as a clade (inclusive of Tetragonolepis),
      although fails to recover any characters supporting the monophyly of the genus
      Dapedium. Dapediids are resolved as stem holosteans, filling a conspicuous gap in
      early neopterygian relationships. Pycnodonts, previously suggested as either stem
      teleosts or the sister group to dapediids, are resolved as a clade on the
      neopterygian stem. Similarities between the new taxon described here and Dapedium
      provide insights into morphological disparity within early members of the group
      suggesting that the ecological expansion of dapediids originated prior to the End
      Triassic extinction-as well as contributing to a growing understanding of
      endocranial anatomy in Palaeozoic and Early Mesozoic actinopterygians.

PMID- 30225041
TI  - Is the eye-movement field confused about fixations and saccades? A survey among
      124 researchers.
AB  - Eye movements have been extensively studied in a wide range of research fields.
      While new methods such as mobile eye tracking and eye tracking in
      virtual/augmented realities are emerging quickly, the eye-movement terminology
      has scarcely been revised. We assert that this may cause confusion about two of
      the main concepts: fixations and saccades. In this study, we assessed the
      definitions of fixations and saccades held in the eye-movement field, by
      surveying 124 eye-movement researchers. These eye-movement researchers held a
      variety of definitions of fixations and saccades, of which the breadth seems even
      wider than what is reported in the literature. Moreover, these definitions did
      not seem to be related to researcher background or experience. We urge
      researchers to make their definitions more explicit by specifying all the
      relevant components of the eye movement under investigation: (i) the oculomotor
      component: e.g. whether the eye moves slow or fast; (ii) the functional
      component: what purposes does the eye movement (or lack thereof) serve; (iii) the
      coordinate system used: relative to what does the eye move; (iv) the
      computational definition: how is the event represented in the eye-tracker signal.
      This should enable eye-movement researchers from different fields to have a
      discussion without misunderstandings.

PMID- 30225042
TI  - A lateral flow immunochromatographic strip test for rapid detection of hexoestrol
      in fish samples.
AB  - A lateral flow immunochromatographic strip test was developed for rapid and
      sensitive on-site detection of hexoestrol (HES) residues in fish samples with
      colloidal gold labelling of the anti-HES monoclonal antibody. The strip is
      composed of a sample pad, a conjugate reagent pad, an absorbent pad and a test
      membrane containing a control line and a test line. The sensitivity (half
      inhibitory concentration, IC50) of the strip in the detection of fish extract
      samples was confirmed to be 1.86 ug kg-1, and the limit of detection value was
      0.62 ug kg-1. For intra-assay and inter-assay reproducibility, recoveries of HES
      spiked samples ranged from 86.3% to 92.3% and 85.8% to 93.4%, coefficients of
      variation were 2.91-4.64% and 4.24-5.17%, respectively. High-performance liquid
      chromatography was employed to confirm the performance of the strip. The strip
      test takes less than 10 min, and thus provides a repaid method for on-site
      detection of HES residues.

PMID- 30225043
TI  - Enhanced cycle stability of a NiCo2S4 nanostructured electrode for
      supercapacitors fabricated by the alternate-dip-coating method.
AB  - Nanostructured nickel cobalt sulfide (NiCo2S4) electrodes are successfully
      fabricated using a simple alternate-dip-coating method. The process involves
      dipping a TiO2 nanoparticles-covered substrate in a nickel/cobalt precursor
      solution and sulfur precursor solution alternately at room temperature. The
      fabricated bimetallic sulfide electrode exhibits a synergetic improvement
      compensating for the disadvantages of the two single metal sulfide electrodes,
      i.e. the poor cycle stability of the nickel sulfide electrode and the low
      specific capacitance (Csp) of the cobalt sulfide electrode. The two capacitive
      properties are optimized by adjusting the ratio of nickel and cobalt
      concentrations in the metal precursor solution, reaching a Csp of 516 F g-1 at a
      current density of 1 mA cm-2, with its retention being 99.9% even after 2000
      galvanostatic charge-discharge cycles.

PMID- 30225044
TI  - Synthesis of zinc oxide nanorods or nanotubes on one side of a microcantilever.
AB  - Cantilevers are really promising sensitive sensors despite their small surface.
      In order to increase this surface and consequently their sensitivity, we
      nanostructured them with zinc oxide (ZnO) nanorods or nanotubes having a diameter
      of approximately 100 nm and a length of 1 um. The nanostructure growth was first
      optimized on a silicon wafer and then transferred to the cantilevers. The ZnO
      nanorods were grown in an autoclave. The centre of the nanorods was dissolved in
      order to obtain nanotubes. The dissolution conditions were optimized in order to
      have the longest etching depth. After 1.25 h in a dissolution solution containing
      0.75 wt% of NH3(aq) and 0.75 wt% of cetyltrimethyl ammonium bromide, the longest
      etching depth was obtained. After the transfer of the syntheses to the
      cantilevers, nanorods/nanotubes grew on both sides of the cantilever, which
      prevents the reflection of the laser allowing the resonance frequency
      measurement. A masking procedure was developed in order to avoid the growth on
      one face of the cantilever of zinc oxide nanostructures. As far as the authors
      are concerned, for the first time, zinc oxide nanotubes were synthesized on only
      one face of cantilevers with optical readout.

PMID- 30225045
TI  - Water, water everywhere: environmental DNA can unlock population structure in
      elusive marine species.
AB  - Determining management units for natural populations is critical for effective
      conservation and management. However, collecting the requisite tissue samples for
      population genetic analyses remains the primary limiting factor for a number of
      marine species. The harbour porpoise (Phocoena phocoena), one of the smallest
      cetaceans in the Northern Hemisphere, is a primary example. These elusive, highly
      mobile small animals confound traditional approaches of collecting tissue samples
      for genetic analyses, yet their nearshore habitat makes them highly vulnerable to
      fisheries by-catch and the effects of habitat degradation. By exploiting the
      naturally shed cellular material in seawater and the power of next-generation
      sequencing, we develop a novel approach for generating population-specific
      mitochondrial sequence data from environmental DNA (eDNA) using surface seawater
      samples. Indications of significant genetic differentiation within a currently
      recognized management stock highlights the need for dedicated eDNA sampling
      throughout the population's range in southeast Alaska. This indirect sampling
      tactic for characterizing stock structure of small and endangered marine mammals
      has the potential to revolutionize population assessment for otherwise
      inaccessible marine taxa.

PMID- 30225047
TI  - The contributions of ankle, knee and hip joint work to individual leg work change
      during uphill and downhill walking over a range of speeds.
AB  - The muscles surrounding the ankle, knee and hip joints provide 42, 16 and 42%,
      respectively, of the total leg positive power required to walk on level ground at
      various speeds. However, each joint's contribution to leg work when walking
      up/downhill at a range of speeds is not known. Determining each biological
      joint's contribution to leg work over a range of speeds and slopes can inform the
      design of biomimetic assistive devices (i.e. prostheses). Twenty healthy adults
      walked 1.00, 1.25 and 1.50 m s-1 on 0 degrees , +/-3 degrees , +/-6 degrees  and
      +/-9 degrees  while we collected kinematic and kinetic data. We calculated
      sagittal plane joint work and individual leg work over the entire stance phase.
      The ratio of ankle joint to total individual leg positive work (summed ankle,
      knee and hip joint work) did not change (0.42) with speed or slope, but the ratio
      of ankle joint to individual leg negative work was 0.38 at -9 degrees , 0.42 at 0
      degrees  and 0.27 at +9 degrees  across all speeds. The ratio of ankle joint to
      total individual leg negative work was 0.41 at 1.00 m s-1 and 0.32 at 1.50 m s-1
      across all slopes. The ratio of knee joint to total individual positive leg work
      (0.22) did not change with speed or slope. The ratio of knee joint to total
      individual leg negative work was 0.39 at 1.00 m s-1 and 0.45 at 1.50 m s-1 across
      all slopes. The ratio of hip joint to total individual leg positive work did not
      change with speed but was 0.34 at -9 degrees , 0.33 at 0 degrees  and 0.37 at +9
      degrees  across all speeds. The ratio of hip joint to total individual leg
      negative work was 0.21 at 1.00 m s-1, and 0.24 at 1.50 m s-1 across all slopes
      and 0.17 at -9 degrees , 0.19 at 0 degrees  and 0.29 at +9 degrees  across all
      speeds. The ankle significantly contributes to walking on slopes and this
      contribution changes during sloped compared with level-ground walking, thus
      assistive devices that provide biomimetic ankle function must adapt to
      accommodate walking at different speeds and slopes; whereas assistive biomimetic
      devices for the knee only need to adapt at different speeds.

PMID- 30225046
TI  - Global demographic history of human populations inferred from whole mitochondrial
      genomes.
AB  - The Neolithic transition has led to marked increases in census population sizes
      across the world, as recorded by a rich archaeological record. However, previous
      attempts to detect such changes using genetic markers, especially mitochondrial
      DNA (mtDNA), have mostly been unsuccessful. We use complete mtDNA genomes from
      over 1700 individuals, from the 1000 Genomes Project Phase 3, to explore changes
      in populations sizes in five populations for each of four major geographical
      regions, using a sophisticated coalescent-based Bayesian method (extended
      Bayesian skyline plots) and mutation rates calibrated with ancient DNA. Despite
      the power and sophistication of our analysis, we fail to find size changes that
      correspond to the Neolithic transitions of the study populations. However, we do
      detect a number of size changes, which tend to be replicated in most populations
      within each region. These changes are mostly much older than the Neolithic
      transition and could reflect either population expansion or changes in population
      structure. Given the amount of migration and population mixing that occurred
      after these ancient signals were generated, we caution that modern populations
      will often carry ghost signals of demographic events that occurred far away from
      their current location.

PMID- 30225048
TI  - Novel magnetic resonance technique for characterizing mesoscale structure of
      trabecular bone.
AB  - Osteoporosis, characterized by increased fracture risk and bone fragility,
      impacts millions of adults worldwide, but effective, non-invasive and easily
      accessible diagnostic tests of the disease remain elusive. We present a magnetic
      resonance (MR) technique that overcomes the motion limitations of traditional MR
      imaging to acquire high-resolution frequency-domain data to characterize the
      texture of biological tissues. This technique does not involve obtaining full two
      dimensional or three-dimensional images, but can probe scales down to the order
      of 40 MUm and in particular uncover structural information in trabecular bone.
      Using micro-computed tomography data of vertebral trabecular bone, we
      computationally validate this MR technique by simulating MR measurements of a
      'ratio metric' determined from a few k-space values corresponding to trabecular
      thickness and spacing. We train a support vector machine classifier on ratio
      metric values determined from healthy and simulated osteoporotic bone data, which
      we use to accurately classify osteoporotic bone.

PMID- 30225049
TI  - Preparation and characterization of fast-curing powder epoxy adhesive at middle
      temperature.
AB  - At present, the disadvantage of powder epoxy adhesive is the limited application
      area. In order to widen the application range of powder epoxy adhesive from heat
      resistant substrates (such as metals) to heat-sensitive substrates (such as
      plastic products, cardboard and wood), it is necessary to decrease the curing
      temperature. In this article, a series of fast-curing powder epoxy adhesives were
      prepared by the melt blending method with bisphenol A epoxy resin (E-20),
      hexamethylenetetramine (HMTA) as a curing agent and 2-methylimidazole (2-MI) as
      an accelerant. The structure and properties of the E-20/HMTA/2-MI systems were
      characterized by Fourier transform infrared, thermogravimetric analysis, dynamic
      mechanical analyser and differential scanning calorimetry (DSC). 2-MI added into
      the E-20/HMTA systems can simultaneously enhance toughness, tensile strength,
      glass transition temperature (Tg) and thermal stability in comparison with the E
      20/HMTA systems. The best mechanical properties were obtained at 100/8/0.6 weight
      ratio of the E-20/HMTA/2-MI systems. DSC experiments revealed that the exothermic
      peak of the E-20/HMTA/2-MI system was about 55 degrees C lower than that of the E
      20/HMTA system. The activation energy of the cure reaction was determined by both
      Kissinger's and Ozawa's methods at any heating rates. The activation energy and
      pre-exponential factor were about 100.3 kJ mol-1 and 3.57 * 1011 s-1,
      respectively. According to the KAS method, the curing time of the E-20/HMTA/2-MI
      systems was predicted by evaluating the relationship between temperature and
      curing time.

PMID- 30225050
TI  - Experimentally induced social threat increases paranoid thinking.
AB  - The ability to attribute intentions to others is a hallmark of human social
      cognition but is altered in paranoia. Paranoia is the most common positive
      symptom of psychosis but is also present to varying degrees in the general
      population. Epidemiological models suggest that psychosis risk is associated with
      low social rank and minority status, but the causal effects of status and group
      affiliation on paranoid thinking remain unclear. We examined whether relative
      social status and perceived group affiliation, respectively, affect live paranoid
      thinking using two large-N (N = 2030), pre-registered experiments. Interacting
      with someone from a higher social rank or a political out-group led to an
      increase in paranoid attributions of harmful intent for ambiguous actions. Pre
      existing paranoia predicted a general increase in harmful intent attribution, but
      there was no interaction with either type of social threat: highly paranoid
      people showed the same magnitude of increase as non-paranoid people, although
      from a higher baseline. We conclude social threat in the form of low social
      status and out-group status affects paranoid attributions, but ongoing paranoia
      represents a lowered threshold for detecting social threat rather than an
      impaired reactivity to it.

PMID- 30225051
TI  - Structural and temporal patterns of the first global trading market.
AB  - Little is known about the structural patterns and dynamics of the first global
      trading market (FGTM), which emerged during the sixteenth century as a result of
      the Iberian expansion, let alone how it compares to today's global financial
      markets. Here we build a representative network of the FGTM using information
      contained in 8725 (handwritten) Bills of Exchange from that time-which were
      (human) interpreted and digitalized into an online database. We show that the
      resulting temporal network exhibits a hierarchical, highly clustered and
      disassortative structure, with a power-law dependence on the connectivity that
      remains remarkably robust throughout the entire period investigated. Temporal
      analysis shows that, despite major turnovers in the number and nature of the
      links-suggesting fast adaptation in response to the geopolitical and financial
      turmoil experienced at the time-the overall characteristics of the FGTM remain
      robust and virtually unchanged. The methodology developed here demonstrates the
      possibility of building and analysing complex trading and finance networks
      originating from pre-statistical eras, enabling us to highlight the striking
      similarities between the structural patterns of financial networks separated by
      centuries in time.

PMID- 30225052
TI  - New insight into the adsorption behaviour of effluent organic matter on organic
      inorganic ultrafiltration membranes: a combined QCM-D and AFM study.
AB  - Adsorption of organic matter on membranes plays a major role in determining the
      fouling behaviour of membranes. This study investigated effluent organic matter
      (EfOM) adsorption behaviour onto poly(vinylidene fluoride) (PVDF) membrane
      blended with SiO2 nanoparticles using quartz crystal microbalance with
      dissipation monitoring (QCM-D) and atomic force microscopy (AFM). The QCM-D
      results suggested that low adsorption of EfOM and an EfOM layer with a non-rigid
      and open structure was formed on SiO2-terminated membrane surfaces.
      Conformational assessment showed that EfOM undergoes adsorption via two steps:
      (i) in the initial stage, a rapid adsorption of EfOM accumulated onto the
      membrane; (ii) the change in dissipation was still occurring when the adsorption
      frequency reached balance, and the layer tended towards a more rearranged or
      organized secondary structure upon adsorption onto the more hydrophilic surface.
      For the AFM force test, when a self-made EfOM-coated probe approached the
      membrane, a 'jump-in' was observed for the hydrophobic membrane after repulsion
      at a small distance, while only repulsive forces were observed for PVDF/SiO2
      membranes. This study demonstrated that the PVDF/SiO2 membrane changed the entire
      filtration process, forming a 'soft' open conformation in the foulant layer.

PMID- 30225053
TI  - Catalytic combustion of isopropanol over Co-ZSM-5 zeolite membrane catalysts in
      structured fixed-bed reactor.
AB  - Catalytic combustion of isopropanol in the structured fixed-bed reactor was
      investigated over Co-ZSM-5 zeolite membrane catalysts. Firstly, ZSM-5 zeolite
      membrane catalysts with different Si/Al ratios were coated onto the surface of
      stainless steel fibres via secondary growth method and wet lay-up paper-making
      method. Then, cobalt oxides were loaded onto the zeolite membranes by
      impregnation method. The performance of catalytic combustion of isopropanol was
      conducted over the prepared zeolite membrane catalysts, and the experimental
      results showed that the catalyst with infinite Si/Al ratio has the highest
      catalytic activity for the combustion with the lowest T90 of isopropanol (285
      degrees C). Finally, the effects of bed structure, feed concentration, gas hourly
      space velocity and reaction temperature on the catalytic performance were
      investigated to analyse the kinetics of isopropanol over the catalyst with
      infinite Si/Al ratio in the structured fixed-bed reactor. The results showed that
      the longer residence time could cause higher reaction contact efficiency of
      isopropanol combustion. T90 of isopropanol can be dramatically decreased by 105
      degrees C in the fixed-bed reactor packed with Co-ZSM-5 zeolite membrane
      catalysts, compared to the fixed-bed reactor packed with granular catalyst.

PMID- 30225054
TI  - Simulation of the nodal flow of mutant embryos with a small number of cilia:
      comparison of mechanosensing and vesicle transport hypotheses.
AB  - Left-right (L-R) asymmetry in the body plan is determined by nodal flow in
      vertebrate embryos. Shinohara et al. (Shinohara K et al. 2012 Nat. Commun.3, 622
      (doi:10.1038/ncomms1624)) used Dpcd and Rfx3 mutant mouse embryos and showed that
      only a few cilia were sufficient to achieve L-R asymmetry. However, the mechanism
      underlying the breaking of symmetry by such weak ciliary flow is unclear. Flow
      mediated signals associated with the L-R asymmetric organogenesis have not been
      clarified, and two different hypotheses-vesicle transport and mechanosensing-are
      now debated in the research field of developmental biology. In this study, we
      developed a computational model of the node system reported by Shinohara et al.
      and examined the feasibilities of the two hypotheses with a small number of
      cilia. With the small number of rotating cilia, flow was induced locally and
      global strong flow was not observed in the node. Particles were then effectively
      transported only when they were close to the cilia, and particle transport was
      strongly dependent on the ciliary positions. Although the maximum wall shear rate
      was also influenced by ciliary position, the mean wall shear rate at the
      perinodal wall increased monotonically with the number of cilia. We also
      investigated the membrane tension of immotile cilia, which is relevant to the
      regulation of mechanotransduction. The results indicated that tension of about
      0.1 MUN m-1 was exerted at the base even when the fluid shear rate was applied at
      about 0.1 s-1. The area of high tension was also localized at the upstream side,
      and negative tension appeared at the downstream side. Such localization may be
      useful to sense the flow direction at the periphery, as time-averaged
      anticlockwise circulation was induced in the node by rotation of a few cilia. Our
      numerical results support the mechanosensing hypothesis, and we expect that our
      study will stimulate further experimental investigations of mechanotransduction
      in the near future.

PMID- 30225056
TI  - The reproductive strategy in a Chloris virgata population in response to
      precipitation regimes.
AB  - Resource availability influences plant growth and reproduction. Here, a
      controlled experiment was conducted in order to evaluate the adaptation response
      of Chloris virgata to different precipitation conditions, and to further predict
      the reproductive strategy in a population of C. virgata under different
      precipitation regimes. Three regimes (low, typical and high) of water addition
      were used to simulate current precipitation patterns. In total 20 individuals for
      each treatment were analysed to compare tiller number, spike traits, seed traits,
      the relationship between seed size and seed number, and so on. In addition, the
      effects of different precipitation regimes on offspring vigour of C. virgata were
      also studied. Results indicated that tiller number, spike number, seed yield and
      seed number were unchanged under different water addition regimes, while seed
      size was about 0.5 mg at typical and high precipitation levels and was higher
      than that in the low precipitation level. The higher seed mass per spike and
      spike mass both occurred at typical and high precipitation levels. Significant
      positive correlations between seed mass and non-seed mass in C. virgata in
      response to precipitation regimes were largely allometric (size dependent), as
      was a significant negative correlation between seed size and seed number at low
      precipitation. The highest germination rates and seedling weights both occurred
      at typical and high precipitation levels. These findings showed that different
      precipitation regimes affected reproductive strategy of C. virgata. Chloris
      virgata will not benefit from low precipitation, while typical and high
      precipitation will improve seed traits and offspring vigour of this species.

PMID- 30225055
TI  - Imaging carbon nanostructures' reactivity: a complementary strategy to define
      chemical structure.
AB  - In the search for the integration of carbon nanostructures in composite and
      functional materials, covalent organic reactions are successfully performed. This
      approach resulted in the construction of tailored chemical interfaces
      facilitating incorporation of nanocarbons. By a combination of different
      characterization techniques, such as high-resolution X-ray photo-spectroscopy,
      thermogravimetric analysis, Raman spectroscopy, UV-vis-nIR, and fluorescence
      spectroscopies, it is possible to identify and quantify the functional moieties
      covalently attached to the carbon frame. However, the determination of the
      structural conformation of functionalized nanostructures remains a difficult
      task. In this work, we present a straightforward methodology to visualize by
      transmission electron microscopy the functional moieties covalently attached to
      the carbon network in carbon nanotubes and graphene. The identification of the
      functionalities occurs in colloidal dispersions by using gold nanoparticles
      (AuNPs) as discriminating markers by molecular recognition or by the direct
      growth of AuNPs on the oxygenated moieties. This methodology, in combination with
      other characterization analysis, is expected to improve the design of
      hierarchical interfaces by the spatial localization of the functionalities
      responsible for colloidal stabilization in solvents with different polarities,
      different from their homogeneous incorporation into different matrices.

PMID- 30225057
TI  - Solution properties and aggregating structures for a fluorine-containing
      polymeric surfactant with a poly(ethylene oxide) macro-monomer.
AB  - A polymeric surfactant (PFSA) was synthesized by the aqueous free-radical
      copolymerization using acrylamide, sodium 2-acrylamido-2-methylpropane sulfonate,
      allyl-capped octylphenoxy poly(ethylene oxide) (PEO) with the polymerization
      degree of 20 (AOP) and 1H,1H,2H,2H-perfluoro-1-decyl p-vinylbenzyl ether (VF).
      PFSA exhibited both the good surface and interfacial activities and the
      thickening behaviour. It could be used in enhanced oil recovery to increase both
      sweep and oil displacement efficiencies. The critical micelle concentration (CMC)
      of PFSA was 0.1 g l-1 in aqueous solution. The spherical micelles with the
      diameter of 100 nm were formed at CMC, and numerous compact worm-shaped micelles
      were observed above CMC. The interfacial tension was 0.027 mN m-1 for the 0.1 g l
      1 PFSA solution containing 5 g l-1 NaCl and 0.209 g l-1 SDBS. The PFSA solutions
      still showed low interfacial tensions at high NaCl concentrations and
      temperatures, respectively, because of the incorporation of both VF and AOP
      containing long PEO.

PMID- 30225058
TI  - Incorporation of reduced graphene oxide into faceted flower-like {001} TiO2 for
      enhanced photocatalytic activity.
AB  - Anatase TiO2 with {001} facets is much more active than that with {101} facets,
      which has been verified via experiments and theoretical calculations. Graphene
      has garnered much attention since it was initially synthesized, due to its unique
      properties. In this study, reduced graphene oxide (RGO)/{001} faceted TiO2
      composites were fabricated via a solvothermal method. The composites were
      characterized by scanning electron microscopy, transmission electron microscopy,
      X-ray diffraction, X-ray photoelectron spectrophotometry, photoluminescence and
      Raman analysis. The results revealed that the graphene oxide was reduced during
      the preparation process of the {001} faceted TiO2, and combined with the surface
      of {001} TiO2. The photocatalytic activities of the composites were evaluated
      through the degradation of basic violet, under both white light (lambda > 390 nm)
      and visible light (lambda = 420 nm) irradiation. The results indicated that the
      photocatalytic activities of the {001} faceted TiO2 were significantly improved
      following the incorporation of RGO, particularly under visible light irradiation.
      Theoretical calculations showed that the band structure of the {001} faceted TiO2
      was modified via graphene hybridization, where the separation of photoinduced
      electron-hole pairs was promoted; thus, the photocatalytic activity was enhanced.

PMID- 30225059
TI  - Soluble hexamethyl-substituted subphthalocyanine as a dopant-free hole transport
      material for planar perovskite solar cells.
AB  - Boron subphthalocyanine (SubPc) has special physical and chemical properties,
      originating from its non-centrosymmetric, near-planar taper structure and large
      conjugated system; it can act as an alternative to the small molecule hole
      transporting material 2,2',7,7'-tetrakis-(N,N-di-p-methoxyphenylamine)-9,9'
      spirobifluorene in perovskite solar cells (PSCs). To achieve a higher solubility
      in common organic solvents and a more suitable highest occupied molecular orbital
      energy level that aligns with the valence band of the perovskite material, a
      SubPc molecule with a hexamethyl substitution at its peripheral position (Me6
      SubPc) was successfully designed and synthesized in a one-step method. Completely
      solution processed PSCs were fabricated with only a small hysteresis, a power
      conversion efficiency of 6.96% and Voc of 0.986 V.

PMID- 30225060
TI  - Molecular dynamics simulation of aluminum nitride deposition: temperature and N :
      Al ratio effects.
AB  - Heteroepitaxial growth of aluminum nitride (AIN) has been explored by
      experiments, but the corresponding growth mechanism is still unrevealed. Here, we
      use molecular dynamics simulations to study effects of temperature and N : Al
      flux ratio on deposited AlN. When the temperature increases from 1000 K to 2000 K
      with an N : Al flux ratio of 2.0, the growth rate of the AlN film decreases. The
      crystallinity of the deposited AlN is distinctly improved as the temperature
      increases from 1000 K to 1800 K and it becomes saturated between 1800 K and 2000
      K. The crystallinity of the deposited film at 1800 K increases with an increase
      in the N : Al flux ratio from 0.8 to 2.4, and this degraded a little at an N : Al
      flux ratio of 2.8. In addition, stoichiometry is closely related to crystallinity
      of deposited films. Film with good crystallinity is connected with a near 50% N
      fraction. Furthermore, the average mean biaxial stress and mean normal stress at
      1800 K with N : Al flux ratios of 2.0, 2.4 and 2.8 are calculated, indicating
      that the deposited film with lowest stress has the best crystal quality and the
      defects appear where stresses occur.

PMID- 30225061
TI  - Development of coating formulation with silica-titania core-shell nanoparticles
      against pathogenic fungus.
AB  - In the present study, we developed an antifungal coating formulation using
      silica, titania and silica-titania core-shell nanoparticles individually. The
      idea behind the synthesis of core-shell nanoparticles was to use the mechanical
      strength of silica and the antimicrobial property of TiO2 together. These
      nanoparticles were characterized by dynamic light scattering, transmission
      electron microscopy, scanning electron microscopy, EDX, FTIR and X-ray
      diffraction. Silica nanoparticles of 92 nm were prepared by the sol-gel process,
      while TiO2 nanoparticles and nano-core-shells were prepared through the
      peptization process with a size of 77 and 144 nm separately. The antifungal
      effect of the prepared nanoparticles was observed in potato dextrose agar media
      using the concentration of nanoparticles at 1 wt%. These nanoparticles were
      incorporated in two types of binder, polyurethane and polyacrylic, with the same
      concentration of nanoparticles. Coatings were applied on tiles, dried and tested
      against pathogenic fungus, and fungus growth reduction was observed up to 7-10
      days. Coatings developed with TiO2 nanoparticles have shown good growth reduction
      of pathogenic fungus, but coatings formulated with silica-titania core-shell
      nanoparticles killed the fungus fusarium completely and have shown around 90%
      growth reduction for acremonium species also.

PMID- 30225062
TI  - An experimental study of deformation and fracture characteristics of shale with
      pore-water pressure and under triaxial cyclic loading.
AB  - The deformation and fracture characteristics of shale in the Changning-Xingwen
      region were experimentally studied under triaxial cyclic loading with a
      controlled pore-water pressure. An RLW-2000M microcomputer-controlled coal-rock
      rheometer was used in the State key Laboratory of coal mine disaster dynamics and
      control in Chongqing University. These experimental results have indicated the
      following. (i) The shale softened after being saturated with water, while its
      failure strength decreased with the increase of axial strain. (ii) A complete
      cyclic loading-unloading process can be divided into four stages under the
      coupling action of axial cyclic loading and pore-water pressure; namely the slow
      or accelerated increasing of strain in the loading stage, and the slow or
      accelerated decreasing of strain in the unloading stage. (iii) The axial plastic
      deformation characteristics were similar when pore-water pressures were set to 2,
      6 and 10 MPa. Nevertheless, the shale softened ostensibly and fatigue damage
      occurred during the circulation process when the pore-water pressure was set to
      14 MPa. (iv) It has been observed that the mean strain and strain amplitude under
      axial cyclic are positively correlated with pore-water pressure, while the
      elastic modulus is negatively correlated with pore-water pressure. As the cycle
      progresses, the trends in these parameters vary, which indicates that the
      deformation and elastic characteristics of shale are controlled by pore-water
      pressure and cyclic loading conditions. (v) Evidenced via triaxial compression
      tests, it was predominantly shear failure that occurred in the shale specimens.
      In addition, axial cyclic loading caused the shale to generate complex secondary
      fractures, resulting in the specimens cracking along the bedding plane due to the
      effect of pore-water pressure. This study provides valuable insight into the
      understanding of the deformation and failure mechanisms of shale under
      complicated stress conditions.

PMID- 30225063
TI  - Comparison of chemical composition in the buds of Aralia elata from different
      geographical origins of China.
AB  - Aralia elata buds contain many nutrients and have a pleasant taste with a unique
      flavour. Previous studies mainly focused on triterpene saponins in the root bark
      of this species, but little information existed concerning other chemical
      components, especially in the buds. To better understand the nutritional value of
      A. elata, we compared total flavonoids, total saponins, phenolic compounds and
      mineral element contents in the buds of A. elata collected from eight different
      geographical regions (S1: Benxi; S2: Linjiang; S3: Pingwu; S4: Enshi; S5:
      Changbaishan; S6: Shangzhi; S7: Xiaoxinganling and S8: Harbin) in China. The
      results showed that the basic composition in the buds presented a wide variation,
      with ash (8.76-10.35%), crude fibre (5.38-11.07%), polysaccharides (33.85-46.79
      mg g-1), total flavonoid content (TFC, 4.06-48.63 mg g-1) and total saponins
      (13.62-27.85 mg g-1). UPLC combined with the LC-MS/MS method was used for the
      phenolic compounds analysis, and 11 phenolic compounds were identified and
      quantified in the eight samples. The total phenolic content in Enshi (S4) was
      significantly higher than others, and quercetin was the predominant phenolic
      compound in this sample. We used ICP-OES to identify and quantify nine mineral
      elements in the buds. The Fe and Cu contents in S5 were much higher than that of
      others. We obtained maximum Mg, Mn, Co and Ni contents in S4, and found rich Zn
      content in S7. Moreover, the maximum estimated quantities of Ca and Sr were found
      in S8. This study indicated that the chemical composition in the buds of A. elata
      was obviously affected by geographical origin. Our results provided an essential
      theoretical basis of quality evaluation of A. elata buds in the food production
      field.

PMID- 30225064
TI  - Zebrafish aggression on the sub-second time scale: evidence for mutual motor
      coordination and multi-functional attack manoeuvres.
AB  - Most animals fight by repeating complex stereotypic behaviours, yet the internal
      structure of these behaviours has rarely been dissected in detail. We
      characterized the internal structure of fighting behaviours by developing a
      machine learning pipeline that measures and classifies the behaviour of
      individual unmarked animals on a sub-second time scale. This allowed us to
      quantify several previously hidden features of zebrafish fighting strategies. We
      found strong correlations between the velocity of the attacker and the defender,
      indicating a dynamic matching of approach and avoidance efforts. While velocity
      matching was ubiquitous, the spatial dynamics of attacks showed phase-specific
      differences. Contest-phase attacks were characterized by a paradoxical sideways
      attraction of the retreating animal towards the attacker, suggesting that the
      defender combines avoidance manoeuvres with display-like manoeuvres. Post
      resolution attacks lacked display-like features and the defender was avoidance
      focused. From the perspective of the winner, game-theory modelling further
      suggested that highly energetically costly post-resolution attacks occurred
      because the winner was trying to increase its relative dominance over the loser.
      Overall, the rich structure of zebrafish motor coordination during fighting
      indicates a greater complexity and layering of strategies than has previously
      been recognized.

PMID- 30225065
TI  - Strain energy analysis of floor heave in longwall gateroads.
AB  - Floor heave in longwall gateroads is a severe issue that affects mining safety
      and efficiency. Researchers, however, have limited understanding on the floor
      heave mechanism because the deformation of post-failure rocks in the floor was
      seldom considered previously. In this study, we developed a theoretical model
      using the strain energy theory to investigate the post-failure deformation of
      rocks. This model was validated before being implemented into a numerical
      modelling package, FLAC3D, for floor heave analysis. Based on a case study of a
      longwall entry employing a stiff-yield pillar configuration, we observe that
      massive floor heave occurs at the entry rib that takes less loads (yield pillar)
      and eventually propagates towards the other rib bearing a significant amount of
      loads (stiff pillar). This observation sheds light on the floor heave mechanism
      in longwall gateroads and has major implications for coal mine ground control.

PMID- 30225066
TI  - New MRI contrast agents based on silicon nanotubes loaded with superparamagnetic
      iron oxide nanoparticles.
AB  - This article describes the preparation and fundamental properties of a new
      possible material as a magnetic resonance imaging contrast agent based on the
      incorporation of preformed iron oxide (Fe3O4) nanocrystals into hollow silicon
      nanotubes (Si NTs). Specifically, superparamagnetic Fe3O4 nanoparticles of two
      different average sizes (5 nm and 8 nm) were loaded into Si NTs of two different
      shell thicknesses (40 nm and 70 nm). To achieve proper aqueous solubility, the
      NTs were functionalized with an outer polyethylene glycol-diacid (600) moiety via
      an aminopropyl linkage. Relaxometry parameters r1 and r2 were measured, with the
      corresponding r2/r1 ratios in phosphate buffered saline confirming the expected
      negative contrast agent behaviour for these materials. For a given nanocrystal
      size, the observed r2 values are found to be inversely proportional to NT wall
      thickness, thereby demonstrating the role of nanostructured silicon template on
      associated relaxometry properties.

PMID- 30225067
TI  - Identification of 16,25-O-diacetyl-cucurbitane F and 25-O-acetyl-23,24
      dihydrocucurbitacin F as novel anti-cancer chemicals.
AB  - Seven new cucurbitane glucosides, hemslepensides J-P (1-7), and two known
      compounds, 16,25-O-diacetyl-cucurbitane F (8) and 25-O-acetyl-23,24
      dihydrocucurbitacin F (9), were isolated from the tubers of Hemsleya
      pengxianensis var. jinfushanensis. The structures of 1-7 were elucidated using
      infrared absorption spectroscopy, nuclear magnetic resonance spectroscopy and
      high-resolution electrospray ionization mass spectrometry. The treatment of HT29
      cells, human colon cancer cells, with compounds 8 and 9 inhibited cell
      proliferation. Further study demonstrated that compounds 8 and 9 induced F-actin
      aggregation, G2/M phase cell cycle arrest and cell apoptosis in HT29 cells. In
      summary, the present study enriched the chemical composition research of H.
      pengxianensis, and suggested that the compounds 8/9 treatment may be a
      potentially useful therapeutic option for colon cancer.

PMID- 30225069
TI  - Fabrication of the heterojunction catalyst BiVO4/P25 and its visible-light
      photocatalytic activities.
AB  - A heterojunction catalyst, BiVO4/P25, was successfully fabricated using a one
      step hydrothermal method. The prepared composite was characterized using XRD,
      XPS, Raman, FT-IR, UV-vis, SEM, HRTEM and PL. The HRTEM pictures revealed that
      the heterostructured composite was composed of BiVO4 and P25, and from the
      pictures of SEM we could see the P25 nanoparticles assembling on the surface of
      flower-shaped BiVO4 nanostructures. The XPS spectra showed that the prepared
      catalyst consisted of Bi, V, O, Ti and C. The photocatalytic activity of
      BiVO4/P25 was evaluated by degraded methyl blue (MB) and tetracycline under
      visible light illumination (lambda > 420 nm), and the results showed that
      BiVO4/P25 composite has a better photocatalytic performance compared with pure
      BiVO4 and the most active c-BiVO4/P25 sample showed enough catalytic stability
      after three successive reuses for MB photodegradation. The enhanced
      photocatalytic performance could mainly be attributed to the better optical
      absorption ability and good absorption ability of organic contaminants.

PMID- 30225068
TI  - Telomeres as integrative markers of exposure to stress and adversity: a
      systematic review and meta-analysis.
AB  - Telomeres have been proposed as a biomarker that integrates the impacts of
      different kinds of stress and adversity into a common currency. There has as yet
      been no overall comparison of how different classes of exposure associate with
      telomeres. We present a meta-analysis of the literature relating telomere
      measures to stresses and adversities in humans. The analysed dataset contained
      543 associations from 138 studies involving 402 116 people. Overall, there was a
      weak association between telomere variables and exposures (greater adversity,
      shorter telomeres: r = -0.15, 95% CI -0.18 to -0.11). This was not driven by any
      one type of exposure, because significant associations were found separately for
      physical diseases, environmental hazards, nutrition, psychiatric illness,
      smoking, physical activity, psychosocial and socioeconomic exposures.
      Methodological features of the studies did not explain any substantial proportion
      of the heterogeneity in association strength. There was, however, evidence
      consistent with publication bias, with unexpectedly strong negative associations
      reported by studies with small samples. Restricting analysis to sample sizes
      greater than 100 attenuated the overall association substantially (r = -0.09, 95%
      CI -0.13 to -0.05). Most studies were underpowered to detect the typical
      association magnitude. The literature is dominated by cross-sectional and
      correlational studies which makes causal interpretation problematic.

PMID- 30225071
TI  - Subjective wet perception assessment of fabrics with different drying time.
AB  - Wet perception involves a complex neurobiological mechanism and it is a crucial
      factor affecting the wear comfort in daily life. A subjective wet perception
      assessment was conducted against wetted fabrics. The assessment method was set to
      demonstrate the sensation felt by the wearer in recovery period after light
      activities, and assumes that there is no further sweat secretion. Twenty
      participants participated in the assessment. Participants were presented with
      fabrics dried with different duration for simulating garments dry during recovery
      period. A new fabric driver was built to simulate body movements during wear. The
      driver drove specimens and reference fabrics on participants' forearms. The two
      arm configuration of the fabric driver helps to enhance the reliability of
      assessment results. The participants were asked to give wetness rating on each
      sample in ratio scale. We conclude that log10 of subjective wetness rating has
      linear relationship with drying time of fabric (DToF) and amount of water in
      fabric. A novel wetness factor (WF) is developed to quantify the effects of wet
      perception and exposure time induced by a drying fabric. WF is the area under
      curve of wetness rating against DToF. A smaller WF indicates that a user suffers
      less from wet sensation.

PMID- 30225070
TI  - Effects of azo dye on simultaneous biological removal of azo dye and nutrients in
      wastewater.
AB  - The potential disrupting effects of Azo dye on wastewater nutrients removal
      deserved more analysis. In this study, 15 days exposure experiments were
      conducted with alizarin yellow R (AYR) as a model dye to determine whether the
      dye caused adverse effects on biological removal of both the dye and nutrients in
      acclimated anaerobic-aerobic-anoxic sequencing batch reactors. The results showed
      that the AYR removal efficiency was, respectively, 85.7% and 66.8% at AYR
      concentrations of 50 and 200 mg l-1, while higher AYR inlet (400 mg l-1) might
      inactivate sludge. Lower removal of AYR at 200 mg l-1 of AYR was due to the
      insufficient support of electron donors in the anaerobic process. However, the
      decolorized by-products p-phenylenediamine and 5-aminosalicylic were completely
      decomposed in the following aerobic stage at both 50 and 200 mg l-1 of AYR
      concentrations. Compared with the absence of AYR, the presence of 200 mg l-1 of
      AYR decreased the total nitrogen removal efficiency from 82.4 to 41.1%, and
      chemical oxygen demand (COD) removal efficiency initially decreased to 68.1% and
      then returned to around 83.4% in the long-term exposure time. It was also found
      that the inhibition of AYR, nitrogen and COD removal induced by a higher
      concentration of AYR was due to the increased intracellular reactive oxygen
      species production, which caused the rise of oxidation-reduction potential value
      and decreased ammonia monooxygenase and nitrite oxidoreductase activities.

PMID- 30225072
TI  - Porous poly-l-lactide-co-E-caprolactone scaffold: a novel biomaterial for vaginal
      tissue engineering.
AB  - The surgical reconstruction of functional neovagina is challenging and
      susceptible to complications. Therefore, developing tissue engineering-based
      treatment methods for vaginal defects is important. Our aim was to develop and
      test a novel supercritical carbon dioxide foamed poly-l-lactide-co-E-caprolactone
      (scPLCL) scaffold for vaginal reconstruction. The scaffolds were manufactured and
      characterized for porosity (65 +/- 4%), pore size (350 +/- 150 um) and elastic
      modulus (2.8 +/- 0.4 MPa). Vaginal epithelial (EC) and stromal cells (SC) were
      isolated, expanded and characterized with flow cytometry. Finally, cells were
      cultured with scPLCL scaffolds in separate and/or co-cultures. Their attachment,
      viability, proliferation and phenotype were analysed. Both cell types strongly
      expressed cell surface markers CD44, CD73 and CD166. Strong expression of CD326
      was detected with ECs and CD90 and CD105 with SCs. Both ECs and SCs attached and
      maintained viability on scPLCL. Further, scPLCL supported the proliferation of
      especially ECs, which also maintained epithelial phenotype (cytokeratin
      expression) during 14-day assessment period. Interestingly, ECs expressed
      uroplakin (UP) Ia, UPIb and UPIII markers; further, UPIa and UPIII expression was
      significantly higher on ECs cultured on scPLCL than on cell culture plastic. In
      conclusion, the scPLCL is potential scaffold for vaginal tissue engineering and
      the results of this study further illustrate the excellent biocompatibility of
      PLCL.

PMID- 30225073
TI  - Castor oil: a suitable green source of capping agent for nanoparticle syntheses
      and facile surface functionalization.
AB  - Castor oil (CO) is an inedible vegetable oil (VO) that has been employed
      extensively as a bioresource material for the synthesis of biodegradable
      polymers, cosmetics, lubricants, biofuels, coatings and adhesives. It is used in
      medicine, pharmaceuticals and biorefineries, due to its versatile chemistry.
      However, there has been less focus on CO as an alternative to toxic and expensive
      solvents, and capping/stabilizing agents routinely used in nanoparticle
      syntheses. It provides a richer chemistry than edible VOs as a solvent for green
      syntheses of nanoparticles. CO, being the only rich source of ricinoleic acid
      (RA), has been used as a solvent, co-solvent, stabilizing agent and polyol for
      the formation of polymer-nanoparticle composites. RA is a suitable alternative to
      oleic acid used as a capping and/or stabilizing agent. Unlike oleic acid, it
      provides a facile route to the functionalization of surfaces of nanoparticles and
      the coating of nanoparticles with polymers. For applications requiring more polar
      organic solvents, RA is more preferred than oleic acid. In this review, we
      discuss the production, chemical and physical properties, triglyceride and fatty
      acid (FA) compositions and applications of CO, focusing on the use of CO and RA
      as well as other VOs and FAs in syntheses of nanoparticles and surface
      functionalization.

PMID- 30225075
TI  - Assessing the accumulated stickiness magnitude from fabric-skin friction: effect
      of wetness level of various fabrics.
AB  - Increasing skin wetness tends to increase fabric-skin adhesion and friction,
      resulting in wear discomfort or skin injuries. Here, the magnitude estimation
      approach was used to assess the stickiness sensation perceived in fabrics. Seven
      fabric types were wetted by putting onto wet 'skin' surface and dried for
      different durations to achieve different wetness levels, simulating wearing
      conditions during the recovery period after sweating. Results showed that the
      relationship between magnitude estimates of stickiness and amount of water
      present in fabric demonstrated a power function. The exponents and constant from
      power regression show the growth rate of stickiness sensation with moisture
      intensity and the perceived stickiness under fixed stimulus intensity,
      respectively. A novel parameter, accumulated stickiness magnitude (ASM),
      describing how much discomfort a wetted fabric offered throughout the drying
      period, was developed. Thin cotton fabrics (fabric W01 and W03), having higher
      saturation level after contacting with wetted skin surface, arouse stronger
      stickiness feeling and their ASM is remarkably higher. The difference in
      stickiness estimates is due to the difference in chemical composition and surface
      geometry. This study suggests us the way to predict perceived stickiness in
      fabrics with different wetness levels which is useful for applications like
      sportswear, intimate apparel or healthcare products.

PMID- 30225074
TI  - On the relationship between maxillary molar root shape and jaw kinematics in
      Australopithecus africanus and Paranthropus robustus.
AB  - Plio-Pleistocene hominins from South Africa remain poorly understood. Here, we
      focus on how Australopithecus africanus and Paranthropus robustus exploited and
      in part-partitioned their environment. Specifically, we explore the extent to
      which first maxillary molar roots (M1) are oriented and thus, by proxy, estimate
      the direction of loads habitually exerted on the chewing surface. Landmark-based
      shape analysis of M1 root reconstructions of 26 South African hominins and three
      East African Paranthropus boisei suggest that A. africanus may have been able to
      dissipate the widest range of laterally directed loads. Paranthropus robustus and
      P. boisei, despite having overlapping morphologies, differ in aspects of root
      shape/size, dento-cranial morphologies, microwear textures and C4 food
      consumption. Hence, while Paranthropus monophyly cannot be excluded, equivalence
      of dietary niche can. The South African hominins occupied distinct ecological
      niches, whereby P. robustus appears uniquely adapted to dissipate antero
      posteriorly directed loads.

PMID- 30225076
TI  - Convenient fabrication of conjugated polymer semiconductor nanotubes and their
      application in organic electronics.
AB  - Organic heterojunction is indispensable in organic electronic devices, such as
      organic solar cells, organic light-emitting diodes and so on. Fabrication of core
      shell nanostructure provides a feasible and novel way to prepare organic
      heterojunction, which is beneficial for miniaturization and integration of
      organic electronic devices. Fabrication of nanotubes which constitute the core
      shell structure in large quantity is the key for the realization of application.
      In this work, a simple and convenient method to prepare nanotubes using
      conjugated copolymer of perylene diimide and dithienothiophene (P(PDI-DTT)) was
      demonstrated. The relationship between preparation conditions (solvent
      atmosphere, solution concentration and pore diameter of templates) and morphology
      of nanostructure was studied systematically. P(PDI-DTT) nanotubes could be
      fabricated in regular shape and large quantity by preparing the solution with
      appropriate concentration and placing anodic aluminium oxide template with
      nanopore diameter of 200 nm in the solvent atmosphere. The tubular structure was
      confirmed by scanning electron microscopy. P(PDI-DTT) nanotubes exhibited
      electron mobility of 0.02 cm2 V-1 s-1 in field-effect transistors under ambient
      condition. Light-emitting nanostructures were successfully fabricated by
      incorporating tetraphenylethylene into polymer nanotubes.

PMID- 30225077
TI  - Mesoporous silica microparticles gated with a bulky azo derivative for the
      controlled release of dyes/drugs in colon.
AB  - Mesoporous silica microparticles were prepared, loaded with the dye safranin O (M
      Saf) or with the drug budesonide (M-Bud) and capped by the grafting of a bulky
      azo derivative. Cargo release from M-Saf at different pH values (mimicking those
      found in the gastrointestinal tract) in the absence or presence of sodium
      dithionite (a reducing agent mimicking azoreductase enzyme present in the colon)
      was tested. Negligible safranin O release was observed at pH 6.8 and 4.5, whereas
      a moderate delivery at pH 1.2 was noted and attributed to the hydrolysis of the
      urea bond that linked the azo derivative onto the external surface of the
      inorganic scaffold. Moreover, a marked release was observed when sodium
      dithionite was present and was ascribed to the rupture of the azo bond in the
      molecular gate. Budesonide release from M-Bud in the presence of sodium
      dithionite was also assessed by ultraviolet-visible spectroscopy and high
      performance liquid chromatography measurements. In addition, preliminary in vivo
      experiments with M-Saf carried out in mice indicated that the chemical integrity
      of the microparticles remained unaltered in the stomach and the small intestine,
      and safranin O seemed to be released in the colon.

PMID- 30225078
TI  - Increasing photoperiod stimulates the initiation of spring migratory behaviour
      and physiology in a facultative migrant, the pine siskin.
AB  - The transition to a migratory state involves coordinated changes in physiology
      and behaviour. In species with regular, predictable (obligate) migrations,
      increasing day length triggers the expression of a spring migratory state and
      androgens play an important role in stimulating its development. By contrast, we
      know little about the environmental cues and endocrine mechanisms that regulate
      migration in species with less predictable (facultative) migrations. Here, we
      tested whether photoperiod stimulates a migratory state in a facultative nomadic
      migrant, the pine siskin (Spinus pinus). We exposed wintering birds to either a
      naturally increasing or short-day photoperiod and measured physiological and
      behavioural changes indicative of a migratory state. We also examined changes in
      circulating hormones that may play a role in the migratory transition. Natural
      day, but not short-day, birds displayed physiological preparations for migration,
      including increases in fat deposition, and showed increased levels of migratory
      restlessness. We found no evidence for a role of corticosterone in the migratory
      transition, but testosterone may be important. This study is the first
      experimental test of the role of photoperiod in regulating facultative migration
      and demonstrates that the predictive cue used by many obligate migrants to time
      spring migration is also important in a facultative migrant.

PMID- 30225079
TI  - Fixation of CO2 along with bromopyridines on a silver electrode.
AB  - Resulting from the drastic increase of atmospheric CO2 concentration day by day,
      global warming has become a serious environmental issue nowadays. The fixation of
      CO2 to obtain desirable, economically competitive chemicals has recently received
      considerable attention. This work investigates the fixation of CO2 along with
      three bromopyridines via a facile electrochemical method using a silver cathode
      to synthesize picolinic acids, which are important industrial and fine chemicals.
      Cyclic voltammetry is employed to investigate the cyclic voltammetric behaviour
      of bromopyridines. In addition, systematic study is conducted to study the
      relationships between the picolinic acids' yield and the electrolysis conditions
      and intrinsic parameters. The results show that the target picolinic acids'
      yields are strongly dependent on various conditions such as solvent, supporting
      electrolyte, current density, cathode material, charge passed, temperature and
      the nature of the substrates. Moreover, in the studied electrode materials such
      as Ag, Ni, Ti, Pt and GC, electrolysis and cyclic voltammetry show that Ag has a
      good electrocatalytic effect on the reduction and carboxylation of bromopyridine.
      This facile electrochemical route for fixation of CO2 provides an indispensable
      reference for the conversion and utilization of CO2 under mild conditions.

PMID- 30225080
TI  - Genetics of a de novo origin of undifferentiated multicellularity.
AB  - The evolution of multicellularity was a major transition in evolution and set the
      stage for unprecedented increases in complexity, especially in land plants and
      animals. Here, we explore the genetics underlying a de novo origin of
      multicellularity in a microbial evolution experiment carried out on the green
      alga Chlamydomonas reinhardtii. We show that large-scale changes in gene
      expression underlie the transition to a multicellular life cycle. Among these,
      changes to genes involved in cell cycle and reproductive processes were
      overrepresented, as were changes to C. reinhardtii-specific and volvocine
      specific genes. These results suggest that the genetic basis for the experimental
      evolution of multicellularity in C. reinhardtii has both lineage-specific and
      shared features, and that the shared features have more in common with C.
      reinhardtii's relatives among the volvocine algae than with other multicellular
      green algae or land plants.

PMID- 30225081
TI  - Kinship influences sperm whale social organization within, but generally not
      among, social units.
AB  - Sperm whales have a multi-level social structure based upon long-term,
      cooperative social units. What role kinship plays in structuring this society is
      poorly understood. We combined extensive association data (518 days, during 2005
      2016) and genetic data (18 microsatellites and 346 bp mitochondrial DNA (mtDNA)
      control region sequences) for 65 individuals from 12 social units from the
      Eastern Caribbean to examine patterns of kinship and social behaviour. Social
      units were clearly matrilineally based, evidenced by greater relatedness within
      social units (mean r = 0.14) than between them (mean r = 0.00) and uniform mtDNA
      haplotypes within social units. Additionally, most individuals (82.5%) had a
      first-degree relative in their social unit, while we found no first-degree
      relatives between social units. Generally and within social units, individuals
      associated more with their closer relatives (matrix correlations: 0.18-0.25).
      However, excepting a highly related pair of social units that merged over the
      study period, associations between social units were not correlated with kinship
      (p > 0.1). These results are the first to robustly demonstrate kinship's
      contribution to social unit composition and association preferences, though they
      also reveal variability in association preferences that is unexplained by
      kinship. Comparisons with other matrilineal species highlight the range of
      possible matrilineal societies and how they can vary between and even within
      species.

PMID- 30225082
TI  - The auxiliary region method: a hybrid method for coupling PDE- and Brownian-based
      dynamics for reaction-diffusion systems.
AB  - Reaction-diffusion systems are used to represent many biological and physical
      phenomena. They model the random motion of particles (diffusion) and interactions
      between them (reactions). Such systems can be modelled at multiple scales with
      varying degrees of accuracy and computational efficiency. When representing
      genuinely multiscale phenomena, fine-scale models can be prohibitively expensive,
      whereas coarser models, although cheaper, often lack sufficient detail to
      accurately represent the phenomenon at hand. Spatial hybrid methods couple two or
      more of these representations in order to improve efficiency without compromising
      accuracy. In this paper, we present a novel spatial hybrid method, which we call
      the auxiliary region method (ARM), which couples PDE- and Brownian-based
      representations of reaction-diffusion systems. Numerical PDE solutions on one
      side of an interface are coupled to Brownian-based dynamics on the other side
      using compartment-based 'auxiliary regions'. We demonstrate that the hybrid
      method is able to simulate reaction-diffusion dynamics for a number of different
      test problems with high accuracy. Furthermore, we undertake error analysis on the
      ARM which demonstrates that it is robust to changes in the free parameters in the
      model, where previous coupling algorithms are not. In particular, we envisage
      that the method will be applicable for a wide range of spatial multi-scales
      problems including filopodial dynamics, intracellular signalling, embryogenesis
      and travelling wave phenomena.

PMID- 30225083
TI  - beta-Cyclodextrin conjugated bifunctional isocyanate linker polymer for enhanced
      removal of 2,4-dinitrophenol from environmental waters.
AB  - In this work, we reported the synthesis, characterization and adsorption study of
      two beta-cyclodextrin (betaCD) cross-linked polymers using aromatic linker 2,4
      toluene diisocyanate (2,4-TDI) and aliphatic linker 1,6-hexamethylene
      diisocyanate (1,6-HDI) to form insoluble betaCD-TDI and betaCD-HDI. The
      adsorption of 2,4-dinitrophenol (DNP) on both polymers as an adsorbent was
      studied in batch adsorption experiments. Both polymers were well characterized
      using various tools that include Fourier transform infrared spectroscopy,
      thermogravimetric analysis, Brunauer-Emmett-Teller analysis and scanning electron
      microscopy, and the results obtained were compared with the native betaCD. The
      adsorption isotherm of 2,4-DNP onto polymers was studied. It showed that the
      Freundlich isotherm is a better fit for betaCD-TDI, while the Langmuir isotherm
      is a better fit for betaCD-HMDI. The pseudo-second-order kinetic model
      represented the adsorption process for both of the polymers. The thermodynamic
      study showed that betaCD-TDI polymer was more favourable towards 2,4-DNP when
      compared with betaCD-HDI polymer. Under optimized conditions, both betaCD
      polymers were successfully applied on various environmental water samples for the
      removal of 2,4-DNP. betaCD-TDI polymer showed enhanced sorption capacity and
      higher removal efficiency (greater than 80%) than betaCD-HDI (greater than 70%)
      towards 2,4-DNP. The mechanism involved was discussed, and the effects of cross
      linkers on betaCD open up new perspectives for the removal of toxic contaminants
      from a body of water.

PMID- 30225084
TI  - Wet chemical synthesis of nanocrystalline hydroxyapatite flakes: effect of pH and
      sintering temperature on structural and morphological properties.
AB  - Wet chemical synthesis of hydroxyapatite (HAp) nanostructures was carried out
      with different solution pH values (9, 10 and 11) and sintering temperatures (300
      degrees C, 500 degrees C, 700 degrees C and 900 degrees C). The effects of pH and
      sintering temperature on the structural and morphological properties of
      nanocrystalline HAp powders were presented. Fourier transform infrared
      spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy
      (SEM) analysis were performed to obtain the crystalline structure, chemical
      composition, morphology and particle size of the HAp powders. The TEM analysis is
      used in order to observe the rod- and flake-like HAp structures. XRD confirms the
      presence of both HAp hexagonal and monetite phases, although the monetite phase
      was less abundant in the resultant powders. Increase in pH reduced the monetite
      phase and enhanced Ca/P ratio from 1.7 to 1.83. Additionally, an increment in
      sintering temperature increased the crystallite size from 20 to 56 nm. The SEM
      analysis revealed the formation of semi-spherical and flake-like HAp structures
      with preferential flake morphology. An increase in pH and sintering temperature
      resulted in the growth and coalescence of crystals resulting in a porous capsular
      morphology. The FTIR analysis confirmed the reduction of carbonate stretching
      modes with an increase in pH and H-O-H antisymmetric stretching mode is
      eliminated for powders sintered at 900 degrees C confirming the formation of
      stable and porous HAp powders.

PMID- 30225085
TI  - Morphological variation under domestication: how variable are chickens?
AB  - The process of domestication has long fascinated evolutionary biologists,
      yielding insights into the rapidity with which selection can alter behaviour and
      morphology. Previous studies on dogs, cattle and pigeons have demonstrated that
      domesticated forms show greater magnitudes of morphological variation than their
      wild ancestors. Here, we quantify variation in skull morphology, modularity and
      integration in chickens and compare those to the wild fowl using three
      dimensional geometric morphometrics and multivariate statistics. Similar to other
      domesticated species, chickens exhibit a greater magnitude of variation in shape
      compared with their ancestors. The most variable part of the chicken skull is the
      cranial vault, being formed by dermal and neural crest-derived bones, its form
      possibly related to brain shape variation in chickens, especially in crested
      breeds. Neural crest-derived portions of the skull exhibit a higher amount of
      variation. Further, we find that the chicken skull is strongly integrated,
      confirming previous studies in birds, in contrast to the presence of modularity
      and decreased integration in mammals.

PMID- 30225086
TI  - Habitual stone-tool-aided extractive foraging in white-faced capuchins, Cebus
      capucinus.
AB  - Habitual reliance on tool use is a marked behavioural difference between wild
      robust (genus Sapajus) and gracile (genus Cebus) capuchin monkeys. Despite being
      well studied and having a rich repertoire of social and extractive foraging
      traditions, Cebus sp. rarely use tools and have never been observed using stone
      tools. By contrast, habitual tool use by Sapajus is widespread. We review theory
      and discuss factors which might explain these differences in patterns of tool use
      between Cebus and Sapajus. We then report the first case of habitual stone tool
      use in a gracile capuchin: a population of white-faced capuchins (Cebus capucinus
      imitator) in Coiba National Park, Panama who habitually rely on hammerstone and
      anvil tool use to access structurally protected food items in coastal areas
      including Terminalia catappa seeds, hermit crabs, marine snails, terrestrial
      crabs and other items. This behaviour has persisted on one island in Coiba
      National Park since at least 2004. From 1 year of camera trapping, we found that
      stone tool use is strongly male-biased. Of the 205 camera trap days where tool
      use was recorded, adult females were never observed to use stone tools, although
      they were frequently recorded at the sites and engaged in scrounging behaviour.
      Stone tool use occurs year-round in this population; over half of all
      identifiable individuals were observed participating. At the most active tool use
      site, 83.2% of days where capuchins were sighted corresponded with tool use.
      Capuchins inhabiting the Coiba archipelago are highly terrestrial, under
      decreased predation pressure and potentially experience resource limitation
      compared to mainland populations-three conditions considered important for the
      evolution of stone tool use. White-faced capuchin tool use in Coiba National Park
      thus offers unique opportunities to explore the ecological drivers and
      evolutionary underpinnings of stone tool use in a comparative within- and between
      species context.

PMID- 30225087
TI  - Using a robotic fish to investigate individual differences in social
      responsiveness in the guppy.
AB  - Responding towards the actions of others is one of the most important behavioural
      traits whenever animals of the same species interact. Mutual influences among
      interacting individuals may modulate the social responsiveness seen and thus make
      it often difficult to study the level and individual variation in responsiveness.
      Here, open-loop biomimetic robots that provide standardized, non-interactive
      social cues can be a useful tool. These robots are not affected by the live
      animal's actions but are assumed to still represent valuable and biologically
      relevant social cues. As this assumption is crucial for the use of biomimetic
      robots in behavioural studies, we hypothesized (i) that meaningful social
      interactions can be assumed if live animals maintain individual differences in
      responsiveness when interacting with both a biomimetic robot and a live partner.
      Furthermore, to study the level of individual variation in social responsiveness,
      we hypothesized (ii) that individual differences should be maintained over the
      course of multiple tests with the robot. We investigated the response of live
      guppies (Poecilia reticulata) when allowed to interact either with a biomimetic
      open-loop-controlled fish robot-'Robofish'-or with a live companion. Furthermore,
      we investigated the responses of live guppies when tested three times with
      Robofish. We found that responses of live guppies towards Robofish were weaker
      compared with those of a live companion, most likely as a result of the non
      interactive open-loop behaviour of Robofish. Guppies, however, were consistent in
      their individual responses between a live companion and Robofish, and similar
      individual differences in response towards Robofish were maintained over repeated
      testing even though habituation to the test environment was detectable.
      Biomimetic robots like Robofish are therefore a useful tool for the study of
      social responsiveness in guppies and possibly other small fish species.

PMID- 30225088
TI  - Parasites and politics: why cross-cultural studies must control for relatedness,
      proximity and covariation.
AB  - A growing number of studies seek to identify predictors of broad-scale patterns
      in human cultural diversity, but three sources of non-independence in human
      cultural variables can bias the results of cross-cultural studies. First, related
      cultures tend to have many traits in common, regardless of whether those traits
      are functionally linked. Second, societies in geographical proximity will share
      many aspects of culture, environment and demography. Third, many cultural traits
      covary, leading to spurious relationships between traits. Here, we demonstrate
      tractable methods for dealing with all three sources of bias. We use cross
      cultural analyses of proposed associations between human cultural traits and
      parasite load to illustrate the potential problems of failing to correct for
      these three forms of statistical non-independence. Associations between parasite
      stress and sociosexuality, authoritarianism, democracy and language diversity are
      weak or absent once relatedness and proximity are taken into account, and
      parasite load has no more power to explain variation in traditionalism,
      religiosity and collectivism than other measures of biodiversity, climate or
      population size do. Without correction for statistical non-independence and
      covariation in cross-cultural analyses, we risk misinterpreting associations
      between culture and environment.

PMID- 30225089
TI  - Effects of amendments on heavy metal immobilization and uptake by Rhizoma
      chuanxiong on copper and cadmium contaminated soil.
AB  - An improved method was applied for remediating cadmium and copper co-contaminated
      soil and reducing the metal concentration in Rhizoma chuanxiong. Pot experiments
      were conducted with six amendments (composed with bentonite, phosphate, humic
      acid, biochar, sepiolite powder, etc.). The results showed that soil pH,
      biological activities (soil enzymatic activities and microbial counts) and R.
      chuanxiong biomass were greatly improved with the addition of amendments in all
      treatments, especially in T3 and T6. Also, amendments effectively decreased the
      concentration of malondialdehyde and H2O2 in R. chuanxiong. In the T3 treatment,
      the bio-available Cd and Cu in soil were significantly decreased by 0.53 and 0.41
      mg kg-1, respectively. Meanwhile, the amendment in T3 reduced Cd and Cu
      accumulation in R. chuanxiong about 45.83 and 39.37%, respectively, compared to
      T0. Moreover, the Fourier transform infrared spectroscopy spectra showed the
      surface functional groups of every amendment. To conclude, this study offers an
      effective and environmental method to reduce metal accumulation in R. chuanxiong
      on heavy metal co-contaminated soil.

PMID- 30225090
TI  - Editorial for 'New talent' collection: introducing New Talent in chemistry and
      material science.
AB  - We introduce 14 articles published as part of the 'New talent' special collection
      of invited articles to showcase some of the exciting work being funded by the
      Royal Society. As Royal Society University Research Fellows or Dorothy Hodgkin
      Fellowship holders, the contributors to this collection are rising stars in their
      areas of research. This collection also illustrates the close collaboration
      between Royal Society Open Science and the Royal Society of Chemistry. The
      collection spans the range of the chemical and material sciences, reflecting the
      breadth of research areas receiving Royal Society grant support.

PMID- 30225092
TI  - Correction to: 'Fluctuations in annual climatic extremes are associated with
      reproductive variation in resident mountain chickadees'.
AB  - [This corrects the article DOI: 10.1098/rsos.171604.].

PMID- 30225091
TI  - Correction to: 'The effect of alkali-soluble lignin on purified core cellulase
      and hemicellulase activities during hydrolysis of extractive ammonia-pretreated
      lignocellulosic biomass'.
AB  - [This corrects the article DOI: 10.1098/rsos.171529.].

PMID- 30225093
TI  - Correction to: 'Intercomparison of photogrammetry software for three-dimensional
      vegetation modelling'.
AB  - [This corrects the article DOI: 10.1098/rsos.172192.].

PMID- 30225094
TI  - Self-esteem, study skills, self-concept, social support, psychological distress,
      and coping mechanism effects on test anxiety and academic performance.
AB  - The purpose of this article is to assess the association of test anxiety and
      academic performance with study skills, coping mechanism, self-concept, self
      esteem, and psychological distress among university and high school students. A
      series of validated measures were administered to 284 Kosovar students, most of
      whom were in college (60.3%). Being in college and social support resulted as
      protective factors for test anxiety. Better study skills, self-concept, and
      psychological distress were indicative of higher test anxiety. Higher levels of
      self-esteem were associated with higher student success. Practical implications
      and research future directions have also been discussed.

PMID- 30225096
TI  - X-ray structure analysis of symmetrically substituted 1,1'-diformyl-ruthenocene.
AB  - 1,1'-Di-formyl-ruthenocene, [Ru(C6H5O)2], crystallizes in the ortho-rhom-bic
      system in the P212121 space group at room temperature. There are two
      crystallographically independent mol-ecules in the asymmetric unit. The cyclo
      penta-dienyl rings have eclipsed configuration. The mol-ecules self-assemble in a
      two-dimensional structure by C-H?O and C-H?pi inter-actions with cisoid relative
      orientations of the two formyl groups. The crystal studied was refined as an
      inversion twin.

PMID- 30225095
TI  - A mixed methods exploratory study of women's relationships with and uses of
      fertility tracking apps.
AB  - Digital self-tracking is rising, including tracking of menstrual cycles by women
      using fertility tracking apps (FTAs). However, little is known about users'
      experiences of FTAs and their relationships with them. The aim of this study was
      to explore women's uses of and relationships with FTAs. This exploratory study
      employed a mixed methods approach, involving the collection and analysis of an
      online survey and follow-up interviews. Qualitative analysis of survey and
      interview data informed hypothesis development. Online surveys yielded 241
      responses and 11 follow-up interviews were conducted. Just over a third of women
      surveyed had experience of using FTAs (89/241) and follow-up interviews were
      conducted with a proportion of respondents (11/241). Four main motivations to use
      FTAs were identified: (a) to observe cycle (72%); (b) to conceive (34%); (c) to
      inform fertility treatment (12%); and (d) as contraception (4%). Analysis of the
      free-text survey questions and interviews using grounded theory methodology
      highlighted four themes underpinning women's relationships with FTAs: (a) medical
      grounding; (b) health trackers versus non-trackers; (c) design; and (d) social
      and ethical aspects. Participants who used other health apps were more likely to
      use FTAs (p = 0.001). Respondents who used contraception were less likely to use
      FTAs compared with respondents who did not use contraception (p = 0.002). FTA
      usage also decreases (p = 0.001) as age increases. There was no association
      between FTA usage and menstrual status (p = 0.259). This research emphasises the
      differing motivations for FTA use. Future research should further explore the
      diverse relationships between different subgroups of women and FTAs.

PMID- 30225097
TI  - Coordination complexes of chromium(0) with a series of 1,3-diphenyl-6-aryl
      fulvenes.
AB  - The synthesis and structural properties of a series of chromium tricarbonyl
      'piano-stool' complexes bearing substituted penta-fulvene ligands were studied.
      The complexes, tricarbon-yl(1,3,6-tri-phenyl-fulvene)chromium(0) benz-ene
      hemisolvate, [Cr(C24H18)(CO)3].0.5C6H6 (I), tricarbon-yl[1,3-di-phen-yl-6-(3
      vinyl-phen-yl)fulvene]chromium(0), [Cr(C26H20)(CO)3] (II), and tricarbon-yl[1,3
      diphenyl-6-(pyren-1-yl)fulvene]chromium(0), [Cr(C34H22)(CO)3] (III), each have a
      distorted octa-hedral geometry, with the fulvene coordinated in a pi-eta2:pi
      eta2:pi-eta2 fashion. Significant deviation of the exocyclic fulvene double bond
      from the cyclo-penta-diene plane accompanies coordination. Evidence of non
      covalent pi-pi inter-actions was observed in both (I) and (III), with centroid-to
      centroid distances ranging from 3.330 (8) to 3.494 (8) A.

PMID- 30225098
TI  - 4-(4-Acetyl-5-methyl-1H-1,2,3-triazol-1-yl)benzo-nitrile: crystal structure and
      Hirshfeld surface analysis.
AB  - The title compound, C12H10N4O, comprises a central 1,2,3-triazole ring (r.m.s.
      deviation = 0.0030 A) flanked by N-bound 4-cyano-phenyl and C-bound acetyl
      groups, which make dihedral angles of 54.64 (5) and 6.8 (3) degrees  with the
      five-membered ring, indicating a twisted mol-ecule. In the crystal, the three
      dimensional architecture is sustained by carbonyl-C=O?pi(triazo-yl), cyano
      C=N?pi(triazo-yl) (these inter-actions are shown to be attractive based on non
      covalent inter-action plots) and pi-pi stacking inter-actions [inter-centroid
      separation = 3.9242 (9) A]. An analysis of the Hirshfeld surface shows the
      important contributions made by H?H (35.9%) and N?H (26.2%) contacts to the
      overall surface, as well as notable contributions by O?H (9.9%), C?H (8.7%), C?C
      (7.3%) and C?N (7.2%) contacts.

PMID- 30225100
TI  - Crystal structure and luminescent properties of bis-[2,6-dimethyl-3-(pyridin-2-yl
      kappaN)pyridin-4-yl-kappaC4](2,2,6,6-tetra-methylhepta-ne-3,5-dionato
      kappa2O,O')iridium(III) ethyl acetate monosolvate.
AB  - In the solvated title compound, [Ir(C12H11N2)2(C11H19O2)].CH3CO2C2H5, the IrIII
      ion adopts a distorted octa-hedral coordination environment resulting from its
      coordination by two C,N-chelating 2,6-dimethyl-3-(pyridin-2-yl)pyridin-4-yl
      ligands and one O,O'-chelating 2,2,6,6-tetra-methylhepta-ne-3,5-dionate ligand.
      The C,N-chelating ligands are perpendicular to each other [dihedral angle between
      the least-squares planes = 87.86 (5) degrees ] and are arranged in a cis-C,C' and
      trans-N,N' fashion. In the crystal, pairwise C-H?pi inter-actions between
      inversion-related IrIII complexes are present, forming a dimeric structure. The
      title complex shows bright bluish-green emission with good quantum efficiency in
      solution at room temperature.

PMID- 30225099
TI  - Crystal structure and Hirshfeld surface analysis of (2E)-3-(2,4-di-chloro-phen
      yl)-1-(2,5-di-chloro-thio-phen-3-yl)prop-2-en-1-one.
AB  - The mol-ecular structure of the title compound, C13H6Cl4OS, consists of a 2,5-di
      chloro-thio-phene ring and a 2,4-di-chloro-phenyl ring linked via a prop-2-en-1
      one spacer. The dihedral angle between the 2,5-di-chloro-thio-phene ring and the
      2,4-di-chloro-phenyl ring is 12.24 (15) degrees . The mol-ecule has an E
      configuration about the C=C bond and the carbonyl group is syn with respect to
      the C=C bond. The mol-ecular conformation is stabilized by intra-molecular C-H?Cl
      contacts, producing S(6) and S(5) ring motifs. In the crystal, the mol-ecules are
      linked along the a-axis direction through face-to-face pi-stacking between the
      thio-phene rings and the benzene rings of the mol-ecules in zigzag sheets lying
      parallel to the bc plane along the c axis. The inter-molecular inter-actions in
      the crystal packing were further analysed using Hirshfield surface analysis,
      which indicates that the most significant contacts are Cl?H/ H?Cl (20.8%),
      followed by Cl?Cl (18.7%), C?C (11.9%), Cl?S/S?Cl (10.9%), H?H (10.1%), C?H/H?C
      (9.3%) and O?H/H?O (7.6%).

PMID- 30225101
TI  - Hirshfeld surface analysis and crystal structure of 7-meth-oxy-5-methyl-2-phenyl
      11,12-di-hydro-5,11-methano-1,2,4-triazolo[1,5-c][1,3,5]benzoxadiazo-cine.
AB  - The title compound, C19H18N4O2, crystallizes with two independent mol-ecules in
      the asymmetric unit. The triazole ring is inclined to the benzene rings by 9.63
      (13) and 87.37 (12) degrees  in one mol-ecule, and by 4.46 (13) and 86.15 (11)
      degrees  in the other. In the crystal, classical N-H?N hydrogen bonds, weak C-H?O
      hydrogen bonds and weak C-H?pi inter-actions link the mol-ecules into a three
      dimensional supra-molecular network. Hirshfeld surface analysis and two
      dimensional fingerprint plots were used to investigate the inter-molecular inter
      actions present in the crystal, indicating that the most important contributions
      for the crystal packing are from H?H (51.4%), H?C/C?H (26.7%), H?O/O?H (8.9%) and
      H?N/N?H (8%) inter-actions.

PMID- 30225102
TI  - Crystal structure of tebipenem pivoxil.
AB  - The mol-ecular structure of the first orally active carbapenem anti-bacterial
      agent, tebipenem pivoxil (systematic name: (2,2-di-methyl-propano-yloxy)methyl
      (4R,5S,6S)-3-{[1-(4,5-di-hydro-1,3-thia-zol-2-yl)azetidin-3-yl]sulfanyl}-6-[(1R)
      1-hy-droxy-eth-yl]-4-methyl-7-oxo-1-aza-bicyclo-[3.2.0]hept-2-ene-2-carboxyl
      ate), C22H31N3O6S2, has been determined and the configurations of the four chiral
      centers validated. The title compound crystallizes in the triclinic space group
      P1 with one mol-ecule in the unit cell. Three out of the four rings adopt planar
      conformations while the thia-zolinyl ring adopts an enveloped conformation. In
      the crystal, O-H?N hydrogen bonds link the mol-ecules into chains along [10].

PMID- 30225103
TI  - The structure of 9-(3-bromo-6-chloro-2-hy-droxy-phen-yl)-10-(2-hy-droxy-ethyl)
      3,6-diphenyl-3,4,5,6,7,9-hexa-hydro-2H-acridine-1,8-dione.
AB  - In the structure of the title compound C33H29BrClNO4, (I), the hexa-hydro-2H
      acridine ring system has a hy-droxy-ethyl substituent on the N atom and a 3-bromo
      6-chloro-2-hy-droxy-phenyl substituent on the central C atom at the 9-position.
      An unusual feature of the mol-ecule is that the substituents at the 3- and 5
      positions of the outer cyclo-hexenone rings are phenyl rings rather than the more
      common dimethyl substituents. C atoms on both of the cyclo-hexenone rings are
      disordered over two sites. In the crystal structure, O-H?O, C-H?O and C
      H?pi(ring) hydrogen bonds combine with an Br-O and unusual C-Br?pi(ring) halogen
      bonds to generate a three dimensional network with mol-ecules stacked along the a
      axis direction.

PMID- 30225104
TI  - A new structural model for NiFe hydrogenases: an unsaturated analogue of a
      classic hydrogenase model leads to more enzyme-like Ni-Fe distance and inter
      planar fold.
AB  - The complex cation in the title compound, (carbonyl-1kappaC)(1eta5-penta-methyl
      cyclo-penta-dien-yl)(MU-2,3,9,10-tetra-methyl-1,4,8,11-tetra-thia-undeca-2,9
      diene-1,11-diido-1kappa2S,S''':2kappa4S,S',S'',S''')ironnickel(Fe-Ni) hexa-fluoro
      phosphate, [FeNi(C10H15)(C11H18S4)(CO)]PF6 or [Ni(L')FeCp*(CO)]PF6, is composed
      of the nickel complex fragment [Ni(L')] coordinated as a metalloligand (using S1
      and S4) to the [FeCp*(CO)]+ fragment, where (L')2- is [S-C(Me)=C(Me)-S-(CH2)3-S
      C(Me)=C(Me)-S]2- and where Cp*- is cyclo-C5(Me)5- (penta-methyl-cyclo-penta-dien
      yl). The ratio of hexa-fluoro-phosphate anion per complex cation is 1:1. The
      structure at 150 K has ortho-rhom-bic (Pbcn) symmetry. The atoms of the complex
      cation are located on general positions (multiplicity = 8), whereas there are two
      independent hexa-fluoro-phosphate anions, each located on a twofold axis (Wyckoff
      position 4c; multiplicity = 4). The structure of the new dimetallic cation
      [Ni(L')FeCp*(CO)]+ can be described as containing a three-legged piano-stool
      environment for iron [Cp*Fe(CO)'S2'] and an approximately square-planar 'S4'
      environment for Ni. The NiS2Fe diamond-shaped substructure is notably folded at
      the S-S hinge: the angle between the NiS2 plane and the FeS2 plane normals is
      64.85 (6) degrees . Largely because of this fold, the nickel-iron distance is
      relatively short, at 2.9195 (8) A. The structural data for the complex cation,
      which contains a new unsaturated 'S4' ligand (two C=C double bonds), provide an
      inter-esting comparison with the known NiFe hydrogenase models containing a
      saturated 'S4'-ligand analogue having the same number of carbon atoms in the
      ligand backbone, namely with the structures of [Ni(L)FeCp(CO)]+ (as the PF6-
      salt, CH2Cl2 solvate) and [Ni(L)FeCp*(CO)]+ (as the PF6- salt), where (L)2- is [S
      CH2-CH2-S-(CH2)3-S-CH2-CH2-S]2- and Cp- is cyclo-penta-dienyl. The saturated
      analogues [Ni(L)FeCp(CO)]+ and [Ni(L)FeCp*(CO)]+ have similar Ni-Fe distances:
      3.1727 (6), 3.1529 (7) A (two independent mol-ecules in the unit cell) and 3.111
      (5) A, respectively, for the two complexes, whereas [Ni(L')FeCp*(CO)]+ described
      here stands out with a much shorter Ni-Fe distance [2.9196 (8) A]. Also,
      [Ni(L)FeCp(CO)]+ and [Ni(L)FeCp*(CO)]+ show inter-planar fold angles that are
      similar between the two: 39.56 (5), 41.99 (5) (independent mol-ecules in the unit
      cell) and 47.22 (9)  degrees , respectively, whereas [Ni(L')FeCp*(CO)]+ possesses
      a much more pronounced fold [64.85 (6) degrees ]. Given that larger fold angles
      and shorter Ni-Fe distances are considered to be structurally closer to the
      enzyme, unsaturation in an 'S4'-ligand of the type (S-C2-S-C3-S-C2-S)2- seems to
      increase structural resemblance to the enzyme for structural models of the type
      [Ni('S4')FeCp R (CO)]+ (Cp R = Cp or Cp*).

PMID- 30225105
TI  - Crystal structure of fac-bis-[bis-(pyridin-2-yl)methan-amine]-iron(II) 1,1,3,3
      tetra-cyano-2-(di-cyano-methyl-idene)propane-1,3-diide, [Fe(dipa)2](tcpd).
AB  - In the title compound, [Fe(C11H11N3)2](C10N6), the FeII cation is coordinated by
      two bis(pyridin-2-yl)methanamine (dipa) ligands and has crystallographic twofold
      symmetry. There are deviations from ideal octa-hedral geometry due to the steric
      requirements of the ligands. The polynitrile 1,1,3,3-tetra-cyano-2-(di-cyano
      methylid-ene)propane-1,3-diide (tcpd2-) dianion is disordered about an inversion
      center and is not coordinated to the Fe atom. The anion is not planar but has a
      propeller shape. In the crystal, weak N-H?N inter-actions between the amine H
      atoms of the dipa ligands and two nitrile groups of the anion form an alternating
      chain of cations and anions related by the C-centering of the unit cell.

PMID- 30225106
TI  - Hexa-aqua-zinc(II) dinitrate bis-[5-(pyridinium-3-yl)tetra-zol-1-ide].
AB  - Hexa-aqua-zinc(II) dinitrate 5-(pyridinium-3-yl)tetra-zol-1-ide,
      [Zn(H2O)6](NO3)2.2C6H5N5, crystallizes in the space group P . The asymmetric unit
      contains one zwitterionic 5-(pyridinium-3-yl)tetra-zol-1-ide mol-ecule, one NO3-
      anion and one half of a [Zn(H2O)6]2+ cation ( symmetry). The pyridinium and tetra
      zolide rings in the zwitterion are nearly coplanar, with a dihedral angle of 5.4
      (2) degrees . Several O-H?N and N-H?O hydrogen-bonding inter-actions exist
      between the [Zn(H2O)6]2+ cation and the N atoms of the tetra-zolide ring, and
      between the nitrate anions and the N-H groups of the pyridinium ring,
      respectively, giving rise to a three-dimensional network. The 5-(pyridinium-3
      yl)tetra-zol-1-ide mol-ecules show parallel-displaced pi-pi stacking inter
      actions; the centroid-centroid distance between adjacent tetra-zolide rings is
      3.6298 (6) A and that between the pyridinium and tetra-zolide rings is 3.6120 (5)
      A.

PMID- 30225107
TI  - Crystal structure of [MU-1kappa2C1,C4:2(1,2,3,4-eta)-1,2,3,4-tetra-phenyl-buta
      1,3-diene-1,4-di-yl]bis-(tri-carbonyl-osmium)(Os-Os).
AB  - In the title complex C34H20O6Os2 or (MU-eta4-C4Ph4)Os2(CO)6, one Os atom is part
      of a metalla-cyclo-penta-diene ring, while the second Os atom is pi-bonded to the
      organic portion of this ring. The distance of 2.7494 (2) A between the two Os
      atoms is typical of an Os-Os single bond. Three carbonyl ligands are attached to
      each Os atom and these six carbonyls adopt an eclipsed conformation. There are no
      bridging or semibridging CO groups. Two carbonyl ligands and all four phenyl
      groups are disordered over two slightly different positions for which each atom
      in the minor components is displaced less than 1 A from the corresponding atom in
      the major components. The refined occupancies of the major com-ponents of the
      carbonyl ligands are 0.568 (16) and 0.625 (13), while those for the phenyl rings
      are 0.50 (3), 0.510 (12), 0.519 (18), and 0.568 (12).

PMID- 30225108
TI  - Crystal structure and Hirshfeld surface analysis of methyl 4-[(E)-2-(5-bromo-2
      meth-oxy-benzyl-idene)hydrazin-yl]-3-nitro-benzoate.
AB  - The title compound, C16H14BrN3O5, is a novel halogen (Br) substituted hydrazine
      derivative. The hydrazine derivatives were the group of compounds with the
      general structure, R1R2C=NNH2 (Uppal et al., 2011 ?), with the central RC=NNH2
      moiety bridging two different groups on both sides. An all-trans configuration of
      the backbone (RC=NNH2) results in an extended mol-ecular conformation. The
      dihedral angle between the 5-bromo-2-meth-oxy-phenyl ring and the nitrophenyl
      ring is 4.4 (3) degrees . Intra-molecular N-H?O inter-actions form S(6) graph-set
      motifs, while C-H?O and C-H?N inter-actions form S(5) graph-set motifs. Symmetry
      related mol-ecules are linked by C-H?O inter-molecular inter-actions forming an
      R21(10) graph-set motif. There are nearly face-to-face directional specific pi-pi
      stacking inter-actions between the centroids of the nitrophenyl ring and the
      benzene ring of the 5-bromo-2-meth-oxy group [centroid-centroid distance = 3.6121
      (5) A and slippage = 1.115 A], which also contributes to the mol-ecular packing.
      The Hirshfeld surface analysis was performed in order to visualize, explore and
      qu-antify the inter-molecular inter-actions in the crystal lattice of the title
      compound.

PMID- 30225109
TI  - Two new Rb-Ga arsenates: RbGa(HAsO4)2 and RbGa2As(HAsO4)6.
AB  - The crystal structures of hydro-thermally synthesized (T = 493 K, 7-9 d) rubidium
      gallium bis-[hydrogenarsenate(V)], RbGa(HAsO4)2, and rubidium digallium
      arsenic(V) hexa-[hydrogenarsenate(V)], RbGa2As(HAsO4)6, were solved by single
      crystal X-ray diffraction. Both compounds have tetra-hedral-octa-hedral framework
      topologies. The M+ cations are located in channels of the respective framework.
      RbGa(HAsO4)2 crystallizes in the RbFe(HPO4)2 structure type (Rc), while
      RbGa2As(HAsO4)6 adopts the structure type of RbAl2As(HAsO4)6 (Rc), which
      represents a modification of the RbFe(HPO4)2 structure type. In this
      modification, one third of the M3+O6 octa-hedra are replaced by AsO6 octa-hedra,
      and two thirds of the voids in the structure, which are usually filled by M+
      cations, remain empty to achieve charge balance.

PMID- 30225110
TI  - Crystal structure and redox potentials of the tppz-bridged {RuCl(bpy)}+ dimer.
AB  - We report the structural and electrochemical characterization of the binuclear
      complex [MU-(C24H16N6){RuCl(C10H8N2)}2](PF6)2, which contains the bis-tridentate
      bridging ligand 2,3,5,6-tetra-kis-(pyridin-2-yl)pyrazine (tppz), the monodentate
      ligand Cl-, and the bidentate ligand 2,2'-bi-pyridine (bpy) {systematic name: MU
      2,3,5,6-tetra-kis-(pyridin-2-yl)pyrazine-bis-[(2,2'-bi-pyridine)-chlorido-ru
      thenium(II)] bis-(hexa-fluorido-phosphate)}. The complete
      [(bpy)(Cl)Ru(tppz)Ru(Cl)(bpy)]2+ dication is generated by crystallographic
      twofold symmetry; the tppz bridging ligand has a significantly twisted
      conformation, with an average angle of 42.4 degrees  between the mean planes of
      adjacent pyridyl rings. The metal-coordinated chloride ligands are in a trans
      configuration relative to each other across the {Ru(tppz)Ru} unit. The RuII ion
      exhibits a distorted octa-hedral geometry due to the restricted bite angle [160.6
      (3) degrees ] of the tppz ligand. For bpy, the bond lengths of the Ru-N bonds are
      2.053 (8) and 2.090 (8) A, with the shorter bond being opposite to Ru-Cl. For the
      tridentate tppz, the Ru-N distances involving the outer N atoms trans to each
      other are 2.069 (8) and 2.072 (9) A, whereas the Ru-N bond involving the central
      N atom has the much shorter length of 1.939 (7) A as a result of the geometric
      constraints and stronger pi-acceptor ability of the pyrazine-centered bridge. The
      Ru-Cl distance is 2.407 (3) A and the intra-molecular distance between Ru centers
      is 6.579 (4) A. In the crystal, weak C-H?Cl and C-H?F inter-actions consolidate
      the packing.

PMID- 30225111
TI  - N-(6-Meth-oxy-pyridin-2-yl)-1-(pyridin-2-ylmeth-yl)-1H-pyrazole-3-carboxamide:
      crystal structure and Hirshfeld surface analysis.
AB  - The title compound, C16H15N5O2, adopts the shape of the letter L with the
      dihedral angle between the outer pyridyl rings being 78.37 (5) degrees ; the
      dihedral angles between the central pyrazolyl ring (r.m.s. deviation = 0.0023 A)
      and the methyl-ene-bound pyridyl and methyoxypyridyl rings are 77.68 (5) and 7.84
      (10) degrees , respectively. Intra-molecular amide-N-H?N(pyrazol-yl) and pyridyl
      C-H?O(amide) inter-actions are evident and these preclude the participation of
      the amide-N-H and O atoms in inter-molecular inter-actions. The most notable
      feature of the mol-ecular packing is the formation of linear supra-molecular
      chains aligned along the b-axis direction mediated by weak carbonyl
      C=O?pi(triazol-yl) inter-actions. An analysis of the calculated Hirshfeld
      surfaces point to the importance of H?H (46.4%), C?H (22.4%), O?H (11.9%) and N?H
      (11.1%) contacts in the crystal.

PMID- 30225112
TI  - Crystal structure of a homoleptic zinc(II) complex based on bis-(3,5-diiso-propyl
      pyrazol-1-yl)acetate.
AB  - Deprotonation of the methyl-ene group in bis-(3,5-diiso-propyl-pyrazol-1
      yl)methane with nBuLi and reaction with carbon dioxide yields lithium bis-(3,5
      diiso-propyl-pyrazol-1-yl)acetate (1). Treatment of 1 with ZnCl2 results in the
      com-pound bis-[bis-(3,5-diiso-propyl-pyrazol-1-yl)acetato]-zinc(II),
      [Zn(C20H31N4O2)2] (2), whose structure has monoclinic (P21/c) symmetry. The ZnII
      ion resides on an inversion center and is coordinated by two bis-(3,5-diiso
      propyl-pyrazol-1-yl)acetate (bdippza) ligands. Each ligand facially coordinates
      the zinc center via kappa3N,N',O coordination modes to form a distorted octa
      hedral complex with four pyrazole N atoms in the basal plane and two carboxyl-ate
      O atoms in the axial sites.

PMID- 30225113
TI  - Synthesis, crystal structure and Hirshfeld surface analysis of a 1D coordination
      polymer catena-poly[[di-aqua-bis-(nicotinamide-kappaN1)nickel(II)]-MU-fumarato
      kappa2O1:O4].
AB  - The reaction of NiCl2 with fumaric acid and nicotinamide in basic solution
      produces the title polymeric complex, [Ni(C4H2O4)(C6H6N2O)2(H2O)2] n . The NiII
      cation, located on an inversion centre, is coordinated by two O atoms of the
      fumarate dianions, two N atoms from nicotinamide ligands and two water mol-ecules
      in a distorted octa-hedral fashion. In the crystal, the fumarate dianions bridge
      the NiII cations, forming polymeric chains propagating along the [101] direction;
      the polymeric chains are further linked by O-H?O, N-H?O and C-H?O hydrogen bonds,
      forming a three-dimensional supra-molecular architecture. Hirshfeld surface
      analyses and two-dimensional fingerprint plots were used to analyse the inter
      molecular inter-actions present in the crystal, indicating that the most
      important contributions for the crystal packing are from H?O/O?H (35.9%), H?H
      (31.7%) and C?C (10.4%) inter-actions.

PMID- 30225114
TI  - Isomorphous diethyl 1-(4-chloro-benz-yl)-4-(4-chloro-phen-yl)-2,2-dioxo
      3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thia-zine-1,3-di-carboxyl-ate and
      its 1-(4-methyl-benz-yl)-4-(4-methyl-phen-yl)-substituted analogue obeying the
      chloro-methyl exchange rule.
AB  - Accurate studies on the effect of substituents on the crystal packing are
      essential for understanding the inter-molecular inter-actions and thus paving the
      way to crystal structure prediction. The crystal structures of diethyl 1-(4
      chloro-benz-yl)-4-(4-chloro-phen-yl)-2,2-dioxo-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo
      [2,1-c][1,4]thiazine-1,3-di-carboxyl-ate, C26H29Cl2NO6S, (I), and its isomorphous
      pair diethyl 1-(4-methyl-benz-yl)-4-(4-methyl-phen-yl)-2,2-dioxo-3,4,6,7,8,8a
      hexa-hydro-1H-pyrrolo-[2,1-c][1,4]thia-zine-1,3-di-carboxyl-ate, C28H35NO6S,
      (II), are described. The mol-ecular aggregation patterns appear to be strikingly
      similar despite changes in the substituents, with a Cl atom in (I) being replaced
      by a methyl group in (II). Inspite of the chemical modifications, the structures
      of (I) and (I) are isomorphous, isostructural and found to obey the chlorine
      methyl exchange rule. Both the structures feature C-H?O hydrogen bonding.
      However, a distinguishing feature between (I) and (II) is observed in the
      conformation of the pyrrole rings where the twist occurs on different C-N bonds.
      Hirshfeld analysis of both structures is presented and discussed.

PMID- 30225115
TI  - Crystal structure of 2,3'-bi-pyridine-2',6'-dicarbo-nitrile.
AB  - The title compound, C12H6N4, crystallizes with four independent mol-ecules (A, B,
      C and D) in the asymmetric unit. The dihedral angles between the two pyridine
      rings in each mol-ecule are 25.25 (8) degrees  in A, 5.51 (9) degrees  in B,
      11.11 (9) degrees  in C and 16.24 (8) degrees  in D. In the crystal, mol-ecules A
      and B are linked by C-H?N hydrogen bonds to form layers extending parallel to the
      ab plane, while mol-ecules C and D are linked by C-H?N hydrogen bonds forming -C
      D-C-D- chains propagating along the b-axis direction. The layers and the chains
      are stacked alternately along the c axis through offset pi-pi and C=N?pi [N-to
      pyridine-centroid distance = 3.882 (2) A] inter-actions, resulting in the
      formation of a supra-molecular framework.

PMID- 30225116
TI  - A structural study of 2,4-di-methyl-aniline derivatives.
AB  - Crystallographic studies of nitro-gen-containing small mol-ecules aid in the
      elucidation of their structure-activity relationships and modes of aggregation.
      In this study, two previously synthesized mol-ecules are crystallographically
      characterized for the first time. Reaction of 2,4-di-methyl-aniline with N-bromo
      succinimide affords the ortho-brominated derivative 2-bromo-4,6-di-methyl-aniline
      (1; C8H10BrN), which sublimates in vacuo to afford crystals featuring hydrogen
      bonded chains as well as Type I halogen-halogen inter-actions. Conversely, alkyl
      ation of two equivalents of 2,4-di-methyl-aniline with 1,2-di-bromo-ethane
      affords a separable mixture of N,N'-bis-(2,4-di-methyl-phen-yl)piperazine (2;
      C20H26N2), which was crystallographically characterized, as well as N,N'-bis-(2,4
      di-methyl-phen-yl)ethyl-enedi-amine (3).

PMID- 30225117
TI  - One-pot synthesis of (1RS,21SR)-diethyl 2-[23-amino-22-eth-oxy-carbonyl-8,11,14
      trioxa-25-aza-tetra-cyclo-[19.3.1.02,7.015,20]penta-cosa-2,4,6,15(20),16,18,22
      heptaen-25-yl]but-2-endioate.
AB  - The title compound, C30H34N2O9 (4), is a product of the Michael reaction of aza
      crown ether with dimethyl acetyl-enedi-carboxyl-ate modified by an addition of
      NH3 (aq.) at 298 K. The aza-14-crown-4-ether ring adopts a bowl conformation. The
      dihedral angle between the planes of the benzene rings fused to the aza-14-crown
      4-ether moiety is 8.65 (5) degrees . The tetra-hydro-pyridine ring has a boat
      conformation. The mol-ecular conformation is supported by one N-H?O and two C-H?O
      intra-molecular hydrogen bonds. Both heterocyclic and amino N atoms have
      essentially planar configurations (sums of the bond angles are 359.35 and 358.00
      degrees ). Compound 4 crystallizes as a racemate consisting of enanti-omeric
      pairs of the 1R,21S diastereomer. In the crystal, mol-ecules of 4 are connected
      by N-H?O hydrogen bonds, forming chains along [100]. According to the PASS
      program (computer prediction of biological activities), compound 4 may exhibit
      anti-allergic (72% probability) and anti-asthmatic (67%) activity, as well as be
      a membrane permeability inhibitor (65%).

PMID- 30225118
TI  - Crystal structure of (methanol-kappaO)[5,10,15,20-tetra-kis-(2-amino-phen
      yl)porphyrinato-kappa4N]zinc(II)-chloro-form-methanol (1/1/1).
AB  - In the crystal structure of the title compound,
      [Zn(C44H32N8)(CH3OH)].CHCl3.CH3OH, the ZnII cation is coordinated by four
      porphyrin N and one methanol O atom within a slightly distorted square-pyramidal
      environment and is shifted out of the porphyrin plane towards the direction of
      the methanol mol-ecule. The methyl group of the coordinating methanol mol-ecule
      is disordered over two sets of sites. The porphyrin backbone is nearly planar and
      the phenyl rings are almost perpendicular to the porphyrin plane. As is typical
      for picket-fence porphyrins, all four ortho substituents of the meso-phenyl
      groups (here the amino groups) are facing to the same side of the porphyrin mol
      ecule. In the crystal structure, two neighbouring porphyrin complexes form
      centrosymmetric dimers that are connected via O-H?N hydrogen bonding. With the
      aid of additional N-H?N and C-H?N hydrogen bonding, these dimers are stacked into
      columns parallel to [010] that are finally arranged into layers parallel to
      (001). Between these layers channels are formed where chloro-form solvent mol
      ecules are located that are connected to the porphyrin complexes by weak C-H?Cl
      hydrogen bonding. There are additional cavities in the structure where some small
      residual electron density is found, indicating the presence of disordered
      methanol mol-ecules, but a reasonable model could not be refined. Therefore the
      contribution of the electron density associated with the methanol solvent mol
      ecule was removed with the SQUEEZE procedure [Spek (2015 ?). Acta Cryst. C71, 9
      18] in PLATON. Nevertheless, the given chemical formula and other crystal data
      take into account the methanol solvent mol-ecule.

PMID- 30225119
TI  - Crystal structure and Hirshfeld surface analysis of (E)-5-phenyl-3-[(pyridin-4-yl
      methyl-idene)amino]-thia-zolidin-2-iminium bromide monohydrate.
AB  - In the cation of the title salt, C15H15N4S+.Br-.H2O, the central thia-zolidine
      ring adopts an envelope conformation with puckering parameters Q(2) = 0.279 (4) A
      and phi(2) = 222.5 (9) degrees . The mean plane of the thia-zolidine ring makes
      dihedral angles of 12.4 (2) and 66.8 (3) degrees  with the pyridine and phenyl
      rings, respectively. The pyridine ring in the title mol-ecule is essentially
      planar (r.m.s deviation = 0.005 A). In the crystal, the cations, anions and water
      mol-ecules are linked into a three-dimensional network, which forms cross layers
      parallel to the (120) and (20) planes via O-H?Br, N-H?Br and N-H?N hydrogen
      bonds. C-H?pi inter-actions also help in the stabilization of the mol-ecular
      packing. Hirshfeld surface analysis and 2D (two-dimensional) fingerprint plots
      indicate that the most important contributions to the crystal packing are from
      H?H (35.5%), C?H/H?C (23.9%), Br?H/H?Br (16.4%), N?H/H?N (10.6%) and S?H/H?S
      (7.9%) inter-actions.

PMID- 30225120
TI  - Bis(3-carbamoylpyridin-1-ium) phosphite mono-hydrate.
AB  - Two of the constituent mol-ecules in the title structure, 2C6H7N2O+.HPO32-.H2O,
      i.e. the phosphite anion and the water mol-ecule, are situated on a symmetry
      plane. The mol-ecules are held together by moderate N-H?O and O-H?N, and weak O
      H?O and C-H?Ocarbon-yl hydrogen bonds in which the amide and secondary amine
      groups, and the water molecules are involved. The structural features are usual,
      among them the H atom bonded to the P atom avoids hydrogen bonding.

PMID- 30225121
TI  - Mol-ecular and crystal structure of methyl 4-methyl-2,2-dioxo-1H-2lambda6,1-benzo
      thia-zine-3-carboxyl-ate.
AB  - The title compound, C11H11NO4S, possesses weak analgesic properties and is a
      source compound for the synthesis of highly active analgesic and anti
      inflammatory compounds. The benzo-thia-zine ring adopts a conformation
      intermediate between twist-boat and sofa. The ester substituent is turned towards
      the endocyclic double bond because of steric repulsion. In the crystal, the mol
      ecules form columns along the [001] direction, bound by N-H?O hydrogen bonds and
      stacking inter-actions.

PMID- 30225122
TI  - Crystal structure and theoretical studies of two pi-conjugated fused-ring
      chalcones: (E)-1-(anthra-cen-9-yl)-3-(9-ethyl-9H-carbazol-3-yl)prop-2-en-1-one
      and (E)-1-(anthracen-9-yl)-3-[4-(9H-carbazol-9-yl)phen-yl]prop-2-en-1-one.
AB  - The title chalcones, C31H23NO and C35H23NO, were synthesized via Claisen-Schmidt
      condensation reactions. Both structures were solved and refined using single
      crystal X-ray diffraction data and optimized at the ground state using the
      density functional theory (DFT) method with the B3LYP/6-311++G(d,p) level. In the
      crystals, pi-pi inter-ations and weak C-H?O and C-H?pi inter-actions are
      observed. The effect of these inter-molecular inter-actions in the solid state
      can be seen by the difference between the experimental and theoretical optimized
      geometrical parameters. The structures have also been characterized by UV-Vis
      spectroscopy. The smallest energy gaps of 2.86 and 2.96 eV enhance the nonlinear
      responses of such mol-ecular systems. Hirshfeld surface analyses and 2D (two
      dimensional) fingerprint plots were used to qu-antify the inter-molecular inter
      actions present in the crystal, indicating that these are the most important
      contribution to the crystal packing.

PMID- 30225123
TI  - Crystal structure and Hirshfeld surface analysis of the 1:3 adduct of tetra-aqua
      trinitrato-neodymium(III) with 3-amino-1,2,4-triazine.
AB  - In the title compound, [Nd(NO3)3(H2O)4].3C3H4N4, neodymium is ten-coordinate with
      a distorted bicapped square-anti-prismatic geometry formed from six O atoms from
      three nitrate ions and four O atoms from four coordinated water mol-ecules. The
      structure also contains neutral 3-amino-1,2,4-triazine mol-ecules which are not
      coordinated to the central metal atom. The coordinated water mol-ecules and
      nitrate ions of adjacent complexes are linked by O-H?O hydrogen bonds to form
      cyclic R22(8) ring motifs, which in turn are further connected via hydrogen bonds
      to generate a sheet-like structure. The triazine mol-ecules are involved in a
      number of hydrogen-bonding inter-actions: N-H?N and O-H?N inter-actions to form
      R33(9) motifs and N-H?N inter-actions to link the organic mol-ecules into chains.
      Weak C-H?O hydrogen bonds also occur between triazine mol-ecules and coordinated
      nitrate atoms. All these inter-molecular contacts contribute to the stabilization
      of the three-dimensional supra-molecular framework. Hirshfeld surface analysis
      shows that N?H/H?N and H?H inter-actions account for 42.9 and 20.6% of the
      surface, respectively.

PMID- 30225124
TI  - Crystal structure of sodium (1S)-d-mannit-1-yl-sulfonate.
AB  - The title salt, Na+.C6H13O9S- [systematic name: sodium (1S,2S,3S,4R,5R)
      1,2,3,4,5,6-hexa-hydroxy-hexane-1-sulfonate], is formed by reaction of d-mannose
      with sodium bis-ulfite (sodium hydrogen sulfite) in water. The anion has an open
      chain structure with the S atom and the C atoms of the carbohydrate chain forming
      an essentially planar zigzag chain in which the absolute values of the torsion
      angles lie between 173.6 (2) and 179.9 (3) degrees . The sodium cations are penta
      -coordinated by O atoms, with one link to a carbohydrate O atom and four to O
      atoms of sulfonate residues in separate anions, thus creating a three-dimensional
      network. The carbohydrate anions are arranged in a head (-SO3-) to head (-SO3-)
      arrangement, thereby forming two parallel sheets linked through coordination to
      sodium ions, with each sheet containing inter-molecular hydrogen bonds between
      the anionic residues. Unusually, the double sheets are not connected to
      neighbouring sets of double sheets, either by ion coordination or inter-molecular
      hydrogen bonding.

PMID- 30225125
TI  - Crystal structure of 2-hy-droxy-3-(prop-2-yn-1-yl)naphthalene-1,4-dione.
AB  - The naphtho-quinone unit of the title compound, C13H8O3, is essentially planar,
      with an r.m.s. deviation of 0.013 A for the non-H atoms. The essentially linear
      propargyl group is tilted by ca 113 degrees  relative to the naphtho-quinone
      plane. In the crystal, mol-ecules are linked via a pair of O-H?O hydrogen bonds,
      forming an inversion dimer. The dimers are further linked via pairs of C-H?O
      hydrogen bonds into a tape structure along [20]. No pi-pi stacking is observed in
      the present case as it could be expected for naphtho-quinone derivatives.

PMID- 30225126
TI  - Crystal structures of the hexa-fluorido-phosphate salts of the isomeric 2-, 3-
      and 4-cyano-1-methyl-pyridinium cations and determination of solid-state inter
      action energies.
AB  - The synthesis and crystal structures of the isomeric mol-ecular salts 2-, 3- and
      4-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, C7H7N2+.PF6-, are reported.
      In 2-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, C-H?F hydrogen bonds form
      chains extending along the c-axis direction, which are associated through C-H?F
      hydrogen bonds and P-F?pi(ring) inter-actions into stepped layers. For 3-cyano-1
      methyl-pyridinium hexa-fluorido-phosphate, corrugated sheets parallel to [001]
      are generated by C-H?F hydrogen bonds and P-F?pi(ring) inter-actions. The sheets
      are weakly associated by a weak inter-action of the cyano group with the six
      membered ring of the cation. In 4-cyano-1-methyl-pyridinium hexa-fluorido
      phosphate, C-H?F hydrogen bonds form a more open three-dimensional network in
      which stacks of cations and of anions are aligned with the b-axis direction.
      Dispersion-corrected density functional theory (DFT-D) calculations were carried
      out in order to elucidate some of the energetic aspects of the solid-state
      structures. The results indicate that the distribution of charge within a mol
      ecular ionic cation can play a large role in determining the strength of a cation
      anion inter-action within a crystal structure. Crystals of 2-cyano-1-methyl
      pyridinium hexa-fluorido-phosphate are twinned by a 180 degrees  rotation about
      the c* axis. The anion in 3-cyano-1-methyl-pyridinium hexa-fluorido-phosphate is
      rotationally disordered by 38.2 (1) degrees  in an 0.848 (3):0.152 (3) ratio.

PMID- 30225127
TI  - Crystal structures of chiral 2-[bis-(2-chloro-eth-yl)amino]-1,3,2-oxaza-phospho
      lidin-2-one derivatives for the absolute configuration at phospho-rus.
AB  - 'Nitro-gen mustard' bis-(2-chloro-eth-yl)amine derivatives (2R,4S,5R)- and
      (2S,4S,5R)-2-[bis-(2-chloro-eth-yl)amino]-3,4-dimethyl-5-phenyl-1,3,2-oxaza-phos
      pho-lidin-2-one (2a and 2b, respectively), C14H21Cl2N2O2P, and (2R,4R)- and
      (2S,4R)-2-[bis-(2-chloro-eth-yl)amino]-4-isobutyl-1,3,2-oxaza-phospho-lidin-2-one
      (3a and 3b, respectively), C10H21Cl2N2O2P, were synthesized as a mixture of
      diastereomers through a 1:1 reaction of enanti-omerically pure chiral amino
      alcohols with bis-(2-chloro-eth-yl)phospho-ramidic dichloride. Flash column
      chromatography yielded diastereomerically pure products, as supported by 31P NMR.
      The crystal structures of 2b and 3b were obtained to determine their absolute
      configuration at phospho-rus, and 31P NMR chemical shift trends are proposed
      based on the spatial relationship of the bis-(2-chloro-eth-yl)amine moiety and
      the chiral substituent of the amino alcohol. Oxaza-phospho-lidinones were
      observed to have a more downfield 31P NMR chemical shift when the aforementioned
      substituents are in a syn configuration and vice versa for when they are anti.

PMID- 30225128
TI  - Crystal structure of 3-(tri-phenyl-phosphoranyl-idene)-2,5-di-hydro-furan-2,5
      dione tetra-hydro-furan monosolvate.
AB  - The title pseudo-polymorph of 3-(tri-phenyl-phospho-ranyl-idene)-2,5-di-hydro
      furan-2,5-dione crystallizes with a tetra-hydro-furan solvent mol-ecule, viz.
      C22H17O3P.C4H8O. The succinic anhydride ring is approximately planar (r.m.s.
      deviation = 0.032 A). The tetra-hydro-furan mol-ecule is disordered over two
      orientations about a pseudo-twofold axis with refined occupancy ratio 0.718
      (4):0.282 (4). In the crystal, C-H?O hydrogen bonds link mol-ecules of the di
      hydro-furan-2,5-dione derivative into chains parallel to the b axis and arranged
      into layers stacked along [100] alternating with hydrogen-bonded tetra-hydro
      furan layers.

PMID- 30225129
TI  - Structural characterization and DFT study of bis-{(S)-2-[(2-hy-droxy-benz
      yl)amino]-3-(4-hy-droxy-phen-yl)propano-ato-kappa2N,O}(1,10-phenanthroline
      kappa2N,N')cadmium(II) tetra-hydrate.
AB  - In the title compound, [Cd(C16H16O3)2(C12H8N2)].4H2O, the Cd ion lies on a
      twofold rotation axis and is chelated by two monodeprotonated residues of the l
      tyrosine-derived ligand (S)-2-[(2-hy-droxy-benz-yl)amino]-3-(4-hy-droxy-phen
      yl)propanoic acid (L) in a kappa2N,O amino acid chelating mode, exhibiting an
      (N,N')-trans disposition, and by 1,10-phenanthroline in a kappa2N,N' mode. The
      latter ligand is also located about the twofold rotation axis that bisects the
      central six-members ring. The phenolic groups remain protonated and non
      coordinating and take part as acceptors in the intra-molecular hydrogen bonds
      with the amino groups of the acido ligands. The Cd ion is six-coordinated in a
      distorted octa-hedral environment. In the crystal, O-H?O hydrogen bonds result in
      the formation of three-dimensional network structures. The title complex has also
      been characterized by IR and 1H NMR spectroscopy and DFT studies. The crystal
      studied was refined as an inversion twin.

PMID- 30225130
TI  - A resonance-assisted intra-molecular hydrogen bond in compounds containing 2-hy
      droxy-3,5-di-nitro-benzoic acid and its various deprotonated forms:
      redetermination of several related structures.
AB  - A large number of structural determinations of compounds containing 2-hy-droxy
      3,5-di-nitro-benzoic acid (I) and its various deprotonated forms, 2-hy-droxy-3,5
      di-nitro-benzoate (II) or 2-carb-oxy-4,6-di-nitro-phenolate (III), are biased.
      The reason for the bias follows from incorrectly applied constraints or
      restraints on the bridging hydrogen, which is involved in the intra-molecular
      hydrogen bond between the neighbouring carb-oxy-lic/carboxyl-ate and oxo/hy-droxy
      groups. This hydrogen bond belongs to the category of resonance-assisted hydrogen
      bonds. The present article suggests corrections for the following structure
      determinations that have been published in Acta Crystallographica: DUJZAK,
      JEVNAA, LUDFUL, NUQVEB, QIQJAD, SAFGUD, SEDKET, TIYZIM, TUJPEV, VABZIJ, WADXOR,
      YAXPOE [refcodes are taken from the Cambridge Structural Database [CSD; Groom et
      al. (2016 ?). Acta Cryst. B72, 171-179]. The structural features of the title mol
      ecules in all the retrieved structures, together with structures that contain 3,5
      di-nitro-2-oxidobenzoate (IV), are discussed. Attention is paid to the
      localization of the above-mentioned bridging hydrogen, which can be situated
      closer to the O atom of the carboxyl-ate/carb-oxy-lic group or that of the hy
      droxy/oxo group. In some cases, it is disordered between the two O atoms. The
      position of the bridging hydrogen seems to be dependent on the pKa (base)
      although with exceptions. A stronger basicity enhances the probability of the
      presence of a phenolate (III). The present article examines the problem of the
      refinement of such a bridging hydrogen as well as that of the hydrogen atoms
      involved in the hy-droxy and primary and secondary amine groups. It appears that
      the best model, in many cases, is obtained by fixing the hydrogen-atom position
      found in the difference electron-density map while refining its isotropic
      displacement parameter.

PMID- 30225131
TI  - Na1.85Mg1.85In1.15(PO4)3 and Ag1.69Mg1.69In1.31(PO4)3 with alluaudite-type
      structures.
AB  - Single crystals of two new phosphates, sodium magnesium indium(III) tris
      (orthophosphate) and silver magnesium indium(III) tris-(orthophosphate), were
      obtained from solid-state reactions. The two phosphates are isotypic and exhibit
      alluaudite-type structures. They are characterized by a cationic disorder of the
      Mg and In sites and a partial occupation of the Na and Ag sites, respectively.
      The structure of both phosphates is made up of chains of edge-sharing [(Mg,In)O6]
      octa-hedra extending parallel to [10]. Adjacent chains are linked by PO4 tetra
      hedra to form a three-dimensional framework delimiting two types of channels
      parallel to [001] in which the monovalent cations are situated. The coordination
      numbers of the Na+ cations are 6 and 8, and for both Ag+ cations 6. The
      corresponding coordination spheres are considerably distorted.

PMID- 30225132
TI  - Inversion dimers dominate the crystal packing in the structure of trimethyl
      citrate (trimethyl 2-hy-droxy-propane-1,2,3-tri-carboxyl-ate).
AB  - Trimethyl citrate, C9H14O7 (systematic name: trimethyl 2-hy-droxy-propane-1,2,3
      tri-carboxyl-ate), 2, was prepared by the esterification of citric acid and
      methanol in the presence of thionyl chloride at 273 K. The bond lengths and
      angles in 2 compare closely with those observed in citric acid. The C-C bonds
      adjacent to the terminal carboxyl groups are significantly shorter than those
      around the central C atom. The central carboxyl-ate group and the hy-droxy group
      occur in the normal planar arrangement with an r.m.s. deviation of 0.0171 A from
      the mean plane involving all six atoms in the central unit. The crystal structure
      is almost completely dominated by the formation of inversion dimers through an O
      H?O hydrogen bond, together with an extensive array of weaker C-H?O contacts.
      These generate a three-dimensional network structure with mol-ecules stacked
      along the c-axis direction.

PMID- 30225133
TI  - Crystal structure of Ti8Bi9O0.25 containing inter-stitial oxygen atoms.
AB  - Single crystals of Ti8Bi9O0.25, titanium bis-muth oxide (8/9/0.25), were obtained
      from a sample prepared by heating a mixture of Ti, TiO2 and Bi powders in an Ar
      atmosphere. Single-crystal X-ray analysis revealed that the introduction of O
      atoms into the structure of Ti8Bi9 retains the space-group type P4/nmm. The
      oxygen site is located within a Ti4 tetra-hedron (point group symmetry m2) that
      is vacant in the Ti8Bi9 crystal structure. The occupancy of this site is 0.25
      (4), and the O-Ti distance is 1.8824 (11) A.

PMID- 30225134
TI  - Crystal structure of the [(1,3-dimesityl-1H-imidazol-3-ium-2-yl)methano
      lato]copper(II) chloride dimer: insertion of formaldehyde into a copper-carbene
      bond.
AB  - The crystal structure of bis-[MU-(1,3-dimesityl-1H-imidazol-3-ium-2-yl)methano
      lato-kappa2O:O]bis-[di-chlorido-copper(II)], [Cu2Cl4(C22H26N2O)2], is reported.
      The complex is assumed to have formed via the insertion of formaldehyde into the
      copper-carbon bond in an N-heterocyclic carbene complex of copper(I) chloride.
      The structure of the binuclear mol-ecule possesses a crystallographic-ally
      centrosymmetric Cu2O2 central core with the O atoms bridging between the CuII
      atoms and thus Z' = 0.5. The copper centres are further ligated by two chloride
      ligands, resulting in the CuII atoms residing in a distorted square-planar
      environment. The Cu-O bond lengths are shorter than those previously reported in
      structures with the same central Cu2O2 motif. The complex displays C-H?Cl inter
      actions involving the H atoms of the heterocycle backbone and the chloride
      ligands of a neighbouring mol-ecule.

PMID- 30225135
TI  - Crystal structure of (S)-1-O-tert-butyl-diphenyl-silylglycerol: eight chiral mol
      ecules in a triclinic cell.
AB  - The asymmetric unit of the title compound {systematic name: 3-[(tert-butyl
      diphenyl-sil-yl)-oxy]propane-1,2-diol, C19H26O3Si}, contains eight chiral mol
      ecules (Z' = 8). These mol-ecules are connected via a complex system of hydrogen
      bonds into an infinite assembly along the [100] axis; hydro-phobic tert-butyl and
      phenyl groups form an external coating of the assembly. These assemblies are
      packed by weak inter-molecular inter-actions in a peculiar formation resembling a
      'header bond' masonry brick wall. Disorder of flexible fragments increases with
      temperature but the same crystal structure exists from 120 to 220 K (and most
      probably to the melting point at 334 K).

PMID- 30225136
TI  - Crystal structure of tetra-kis-(MU2-(E)-2,4-di-bromo-6-{[2-(pyridin-2-yl)eth
      yl]imino-meth-yl}phen-olato)trizinc bis-(perchlorate) aceto-nitrile disolvate.
AB  - The title compound, [Zn3(C14H11Br2N2O)4](ClO4)2.2CH3CN, crystallizes as a
      symmetrical trinuclear cation with all three metal atoms being located on a
      twofold rotation axis. It contains a tetra-hedral ZnII atom that bridges two six
      coordinate ZnII atoms. The complex contains N- and O-donor atoms of four
      tridentate 2,4-di-bromo-6-{[2-(pyridin-2-yl)eth-yl]imino-meth-yl}phenolate
      ligands. The ratio of ZnII atoms to ligands is 3:4. The two terminal ZnII cations
      adopt distorted octa-hedral geometries and the central ZnII cation adopts a
      distorted tetra-hedral geometry. In the cation there are pi-pi inter-actions
      between the di-bromo-phenyl rings, as well as halogen-bonding inter-actions
      between the di-bromo-phenyl rings in the cation, which stabilize its
      conformation. In addition, there are C-H?O inter-actions between the anions and
      both the cations and solvent mol-ecules as well as C-H?N inter-actions between
      the cation and solvent mol-ecules. These inter-species inter-actions link the
      cations, anions and solvent mol-ecules into a complex three-dimensional array.

PMID- 30225137
TI  - Crystal structure of bis-(pivaloyl-hydroxamato-kappa2O,O')copper(II).
AB  - Reaction of copper(II) nitrate with pivaloyl-hydroxamic acid yielded the title
      compound, [Cu(pivHA)2] (where pivHA- is pivaloyl hydroxamate, C5H10NO2). The
      centrosymmetric mononuclear complex consists of a CuII ion, which is located on a
      center of inversion, with two coordinated pivaloyl hydroxamate monoanions. The
      CuII ion has a square-planar coordination environment consisting of four O atoms 
      two carbonyl O atoms and two hydroxamate O atoms from two hydroxamate pivHA-
      ligands. The pivHA- anions are coordinated to copper(II) in a trans-mode, forming
      two five-membered O,O'-chelate rings.

PMID- 30225138
TI  - Inhibitory Activity and Docking Analysis of Antimalarial Agents from Stemona sp.
      toward Ferredoxin-NADP+ Reductase from Malaria Parasites.
AB  - Ferredoxin-NADP+ reductases (FNRs, EC 1.18.1.2) were found in the plastids of
      Plasmodium and have been considered as a target for the development of new
      antimalarial agents. Croomine, epi-croomine, tuberostemonine, javastemonine A,
      and isoprotostemonine are isolated alkaloids from the roots of Stemona sp. and
      their inhibitory effect on FNRs from Plasmodium falciparum (PfFNR) was
      investigated. Croomine showed the highest level of inhibition (33.9%) of electron
      transfer from PfFNR to PfFd, while tuberstemonine displayed the highest level of
      inhibition (55.4%) of diaphorase activity of PfFNR. Docking analysis represented
      that croomine is located at the middle position of PfFNR and PfFd. Croomine from
      S. tuberosa appeared to have potential as an antimalarial agent.

PMID- 30225139
TI  - Evaluation of Reliability and Validity of Three Common Dry Eye Questionnaires in
      Chinese.
AB  - Purpose: To investigate the psychometric properties of three commonly used dry
      eye questionnaires including McMonnies Questionnaire (MQ), the Ocular Surface
      Disease Index (OSDI), and the Salisbury Eye Evaluation Questionnaire (SEEQ) in
      Chinese. Methods: This prospective cross-sectional study was conducted at the Eye
      Hospital of Wenzhou Medical University. Ninety-eight participants completed three
      questionnaires in a random order. Ophthalmic examinations including tear break-up
      time, corneal fluorescein staining score, and Schirmer I test were performed.
      Reliability, validity, and accuracy were assessed for three questionnaires.
      Results: There were 35 mild-to-moderate dry eye patients, 14 severe dry eye
      patients, and 49 non-dry eye patients. The Cronbach alpha of MQ, OSDI, and SEEQ
      was 0.54, 0.74, and 0.76, respectively, and the intraclass correlation
      coefficients were 0.91, 0.90, and 0.94, respectively. There were significant
      differences (P < 0.05) in MQ and OSDI scores among different groups, but there
      were no statistically significant differences between the mild-to-moderate group
      and the severe group in terms of SEEQ scores. With cutoff values for abnormal MQ
      of 15, OSDI of 27.2, and SEED of 1, respectively, good dry eye diagnostic
      accuracies were obtained. Conclusions: The three questionnaires showed fair
      accuracy in the diagnosis of dry eye. The cutoff values of OSDI changed when
      applied to Chinese people.

PMID- 30225140
TI  - Emergency Laparotomy in the Critically Ill: Futility at the Bedside.
AB  - Background: Critically ill patients are often evaluated for an intra-abdominal
      catastrophe. In the absence of a preoperative diagnosis, abdominal exploration
      may be offered despite desperate circumstances. We hypothesize that (1) abdominal
      exploration for such patients is associated with a high mortality and (2)
      commonly obtained physiologic measures at laparotomy anticipate mortality.
      Methods: All acute care surgery (ACS) patients undergoing emergency laparotomy at
      a quaternary referral center during a 3-year period were reviewed. Inclusion was
      defined by emergency laparotomy in the operating room (OR) in a patient with an
      American Society of Anesthesiologists (ASA) score >=4 or bedside laparotomy in
      the ICU (BSL). Mortality was the primary endpoint and was stratified by
      demographics, admitting service, surgical findings, and physiology. Comparisons
      between OR and BSL were by Fisher's exact and Mann-Whitney tests. Results: 144
      patients underwent emergency laparotomy (45 BSL vs. 99 OR). Overall mortality was
      55.6% (77.8% BSL vs. 45.5% OR; p < 0.001). Mortality by admitting service was
      cardiac 71.4% (n=42), medical 70% (n=30), ACS 42% (n=50), and other 36.4% (n=22)
      services. Preoperative lactate levels were higher in nonsurvivors (2.7 vs. 8.5
      mmol/L, p < 0.001), as was vasopressor use (62.5% vs. 97.5%, p < 0.001), acute
      kidney injury (51.6% vs. 72.5%, p < 0.01), leukocytosis (53.1% vs. 71.3%, p <
      0.04), and anemia (45.3% vs. 71.3%, p < 0.01). The presence of any identifiable
      abdominal pathology established a 90% mortality rate. Conclusions: The need for
      BSL portends an extremely high mortality rate and is likely useful in
      preintervention counselling. Emergency OR laparotomy leads to mortality in nearly
      half of such patients and is anticipatable based on concurrent abnormal
      physiology.

PMID- 30225141
TI  - Strangulated Hernia Can Be a Risk Factor of Seroma following Laparoscopic
      Transabdominal Preperitoneal Repair.
AB  - Purposes: Seroma is a postoperative complication following laparoscopic
      transabdominal preperitoneal repair (TAPP) for inguinal hernioplasty. Seroma
      naturally resolves in most cases, but it can lead to an increased amount of
      visits to the outpatient clinic and can result in anxiety of the patient. Local
      inflammation of the inguinal area is etiology of seroma formation. Strangulated
      hernia involves severe inguinal pain and can lead to severe inflammation and
      subsequent seroma. There have been no reports demonstrating the links of seroma
      and strangulated hernia. This study aimed to retrospectively evaluate the risk of
      seroma after TAPP and to identify the association between strangulated hernia and
      seroma. Methods: We treated 300 inguinal hernias by TAPP between 2013 and 2016 at
      Kurashiki Central Hospital. We used the Chi-square test. Factors significant in
      each association were further examined using multiple subsequent logistic
      regressions. Results: A total of 222 hernias were eligible for analysis. The
      incidence of seroma was 11% (n=25). There were nine cases of strangulated
      hernias, and three (33%) resulted in seroma. The ratio of strangulated hernia of
      seroma group is significantly high (p<0.03). Multiple subsequent logistic
      regressions showed that strangulated hernia was associated with a significantly
      increased risk for seroma formation (p = 0.023; OR 6.564; 95% CI 1.29-33.3).
      Conclusion: This study shows that strangulated hernia can be a risk factor in
      seroma formation. This risk should be incorporated into a management plan of TAPP
      for strangulated hernia, with careful consideration of patients' concerns.

PMID- 30225142
TI  - Patient-Reported and Performance Outcomes Significantly Improved in Elderly
      Patients with Vestibular Impairment following Rehabilitation: A Retrospective
      Study.
AB  - Objective: To describe the results of a vestibular rehabilitation (VR) program in
      the timed up and go (TUG), gait speed (GS), and dizziness handicap inventory
      (DHI) scores for elderly vestibular patients in a developing country. Methods:
      Descriptive study with retrospective data collected from the clinical records of
      vestibular patients. The following information was recorded: sex, age, type of
      vestibular disorder, DHI score, and performance in TUG and GS, before and after
      participation in a VR program taking place from January 1 to August 30, 2017. The
      VR program consisted of 10 twice weekly sessions in the clinic and daily
      exercises at the patient's home. We used Student's t-test for paired and
      Wilcoxon's test according to the data distribution. The level of significance was
      5%. Results: Data from 57 patients (49 females; 78 +/- 5.8 years old) were used.
      There were statistically significant differences in TUG (12.52 versus 11.56), GS
      (0.81 versus 0.90 m/s), DHI total handicap (46 versus 24), physical (14 versus
      8), emotional (14 versus 6), and functional (18 versus 12) domains. Conclusion:
      The functional outcome measures reported, including TUG, gait speed, and DHI,
      reflect statistically significant improvements in elderly patients after
      vestibular rehabilitation; the DHI improvements are clinically relevant.

PMID- 30225145
TI  - The Impact of Whole Body Vibration Therapy on Spasticity and Disability of the
      Patients with Poststroke Hemiplegia.
AB  - Objective: To determine if whole body vibration therapy (WBV) effectively
      improves functional outcome in patients with poststroke hemiplegia. Materials and
      Methods: In this single-blind RCT, WBV group (n = 10) had 40 hz frequency/4 mm
      amplitude vibration during 5 minutes/session, 3 days a week, for a duration of 4
      weeks. The control group (n = 11) had no vibration therapy for the same duration
      while standing on the same platform. Patients in both of the groups did 15
      minutes of stretching and active range of motion exercises before the
      intervention. Outcome measures were Modified Ashworth Scale (MAS), Functional
      Independence Measurement (FIM), and Timed 10-Meter Walk Test (10 mWT). Results:
      Only 10 mWT improved at the 1st week (p = 0.002), 1st month (p < 0.001), and 3rd
      month (p < 0.001) in favor of the intervention group. There was positive
      correlation also between 10 mWT and ankle spasticity (p < 0.001, r = 0.931).
      Conclusion: This study suggests that WBV therapy may be a complementary therapy
      in gait rehabilitation and functional outcome of the patients with calf muscle
      spasticity.

PMID- 30225144
TI  - Left Right Judgement Task and Sensory, Motor, and Cognitive Assessment in
      Participants with Wrist/Hand Pain.
AB  - The Left Right Judgement Task (LRJT) involves determining if an image of the body
      part is of the left or right side. The LRJT has been utilized as part of
      rehabilitation treatment programs for persons with pain associated with
      musculoskeletal injuries and conditions. Although studies often attribute changes
      and improvement in LRJT performance to an altered body schema, imaging studies
      suggest that the LRJT implicates other cortical regions. We hypothesized that
      cognitive factors would be related to LRJT performance of hands and feet and that
      sensory, motor, and pain related factors would be related to LRJT in the affected
      hand of participants with wrist/hand pain. In an observational cross-sectional
      study, sixty-one participants with wrist/hand pain participated in a study
      assessing motor imagery ability, cognitive (Stroop test), sensory (Two-Point
      Orientation Discrimination, pressure pain thresholds), motor (grip strength,
      Purdue Pegboard Test), and pain related measures (West Haven Yale
      Multidimensional Pain Inventory) as well as disability (Disability of the Arm,
      Shoulder and Hand). Multiple linear regression found Stroop test time and motor
      imagery ability to be related to LRJT performance. Tactile acuity, motor
      performance, participation in general activities, and the taking of pain
      medications were predictors of LRJT accuracy in the affected hand. Participants
      who took pain medications performed poorly in both LRJT accuracy (p=0.001) and
      reaction time of the affected hand (p=0.009). These participants had poorer
      cognitive (p=0.013) and motor function (p=0.002), and higher pain severity scores
      (p=0.010). The results suggest that the LRJT is a complex mental task that
      involves cognitive, sensory, motor, and behavioural processes. Differences
      between persons with and without pain and improvement in LRJT performance may be
      attributed to any of these factors and should be considered in rehabilitation
      research and practice utilizing this task.

PMID- 30225143
TI  - Dilating Vascular Diseases: Pathophysiology and Clinical Aspects.
AB  - Atherosclerotic disease of the vessels is a significant problem affecting
      mortality and morbidity all over the world. However, dilatation of the vessels
      either in the arterial system or in the venous territory is another vessel
      disease. Varicocele, pelvic, and peripheral varicose veins and hemorrhoids are
      aneurysms of the venous vascular regions and have been defined as dilating venous
      disease, recently. Coronary artery ectasia, intracranial aneurysm, and abdominal
      aortic aneurysm are examples of arterial dilating vascular diseases. Mostly, they
      have been defined as variants of atherosclerosis. Although there are some
      similarities in terms of pathogenesis, they are distinct from atherosclerotic
      disease of the vessels. In addition, pathophysiological and histological
      similarities and clinical coexistence of these diseases have been demonstrated
      both in the arterial and in the venous system. This situation underlies the
      thought that dilatation of the vessels in any vascular territory should be
      considered as a systemic vessel wall disease rather than being a local disease of
      any vessel. These patients should be evaluated for other dilating vascular
      diseases in a systematic manner.

PMID- 30225146
TI  - Preoperative Fasting Guidelines in Children: Should They Be Revised?
AB  - Children presenting with ingestion of foreign bodies need gastroscopy as a
      primary management modality. A controversy lies regarding guidelines for
      preoperative fasting among children with low risk of aspiration and
      intraoperative complications. This case report represents cases of children who
      ingested foreign bodies and underwent fasting at different times preoperatively.
      With mounting evidence questioning the benefits of long durations of fasting in
      decreasing the risk of aspiration and with studies showing that fasting for more
      than 2 hours after ingestion of clear fluid does not significantly alter gastric
      pH or volume, these incidental findings raise the question of whether it is safe
      to keep children NPO, for a shorter duration before the administration of
      anesthesia. In addition, this report shows that current guidelines are in need of
      revision.

PMID- 30225147
TI  - Bevacizumab: A Rare Cause of Nonischemic Cardiomyopathy.
AB  - Left ventricular dysfunction is a rare side effect of bevacizumab occurring in 2
      4% of cases. We report the case of a 68-year-old woman who presented to the
      emergency department (ED) with sudden onset of shortness of breath, orthopnea,
      and paroxysmal nocturnal dyspnea. She was tachypneic and in respiratory distress.
      Physical examination revealed jugular venous distention, diffuse expiratory
      wheeze, and bipedal edema. She had been started on bevacizumab for the treatment
      of hereditary hemorrhagic telangiectasia 1 month prior to presentation.
      Laboratory tests revealed BNP of 1697 pg/ml with slightly elevated troponin 0.05
      ng/ml. Chest X-ray showed interstitial edema with cardiomegaly, and transthoracic
      echocardiogram showed ejection fraction of 30% with global hypokinesia. Left
      heart catheterization revealed widely patent coronary arteries. Flash pulmonary
      edema secondary to acute left ventricular dysfunction in this case was attributed
      to recent treatment with bevacizumab after ruling out other possible etiologies.
      This case highlights the importance of early recognition of this rare but
      potentially reversible side effect of bevacizumab to prevent long-term sequelae.

PMID- 30225148
TI  - Coronary Artery Ectasia Presenting as a Non-ST Elevation Myocardial Infarction in
      a Young Adult: Case Presentation and Literature Review.
AB  - While acute coronary syndromes most commonly occur secondary to unstable
      atherosclerotic plaque, coronary aneurysms, also known as coronary artery ectasia
      (CAE), represent a less common etiology. Whereas coronary atherosclerosis
      accounts for about 50% of CAE, the remaining 50% are either congenital or
      secondary to a host of inflammatory and connective tissue disorders, with
      Kawasaki disease being a well-known association. Patients with CAE have worse
      outcomes than the general population regardless of the presence of associated
      atherosclerotic coronary artery disease. We report the case of a young male
      presenting with chest pain, a right bundle branch block on electrocardiography,
      an elevated troponin level, and a regional wall motion abnormality on
      echocardiography who is found to have diffuse coronary artery ectasia on coronary
      angiography and is managed medically with dual antiplatelet therapy.

PMID- 30225149
TI  - Purpura Fulminans and Septic Shock due to Capnocytophaga Canimorsus after Dog
      Bite: A Case Report and Review of the Literature.
AB  - Primary infection by Capnocytophaga canimorsus after dog bite is rare but may be
      difficult to identify and rapidly lethal. We describe a case of fatal septic
      shock with fulminant purpura occurred in a patient without specific risk factor
      two days after an irrelevant dog bite. The patient was brought to hospital
      because of altered mental status, fever, and abdominal pain. In a few hours
      patient became hypoxic and cyanotic. The patient became extremely hypotensive
      with shock refractory to an aggressive fluid resuscitation (40 ml/kg
      crystalloids). She received vasoactive drugs, antibiotic therapy, and blood
      purification treatment, but cardiac arrest unresponsive to resuscitation
      maneuvers occurred. Case description and literature review demonstrated that,
      also in patients without specific risk factors, signs of infection after dog bite
      should be never underestimated and should be treated with a prompt antibiotic
      therapy initiation even before occurrence of organ dysfunction.

PMID- 30225150
TI  - Positive Seatbelt Sign with Avulsed Leiomyoma following Motor Vehicle Accident
      Leading to Hemoperitoneum.
AB  - A positive seatbelt sign following a motor vehicle accident is associated with an
      increased risk of intra-abdominal injury and hemoperitoneum. Injury to the uterus
      in reproductive-age women can also occur. In this report, we describe a 29-year
      old nulligravida female who presented to the emergency room following a motor
      vehicle accident at freeway speeds. A positive seatbelt sign was noted, and a
      focused assessment with sonography for trauma revealed hemoperitoneum with an
      incidental finding of uterine leiomyomata. Upon exploratory laparotomy, a free
      floating intraperitoneal mass was identified as an avulsed uterine leiomyoma. A
      uterine laceration containing a subserosal leiomyoma was also identified. The
      gynecological team was consulted, and a myomectomy of the subserosal leiomyoma
      followed by a closure of the uterine laceration was performed. The patient was
      transfused with a total of three units of packed red blood cells and two units of
      fresh frozen plasma. The postoperative course was without major complication. A
      positive seatbelt sign and hemoperitoneum in a reproductive-age woman with
      leiomyomata should increase the clinical suspicion for uterine injury and
      decrease the threshold for obtaining a gynecological consultation.

PMID- 30225151
TI  - When the Benign Pneumatosis Intestinalis Becomes No Longer Benign: A Rare Case of
      Bowel Perforation in a Patient with Systemic Sclerosis.
AB  - Systemic sclerosis is a multisystem disease featured with autoimmunity and organ
      fibrosis. Although gastrointestinal (GI) tract involvement is common in patients
      with systemic sclerosis, colonic perforation is extremely rare. Benign
      pneumatosis intestinalis, a phenomenon more frequently seen in rheumatologic
      conditions, makes the diagnosis of colonic perforation even more challenging. We
      report a unique case of colonic perforation in a patient with chronic systemic
      sclerosis. This patient initially presented with mild abdominal pain and
      hematemesis. Urgent upper endoscopy was unremarkable and radiology showed stable
      pneumatosis intestinalis. Due to worsening abdominal pain, laparotomy exploration
      was performed and colonic perforation with transmural ischemic necrosis was
      found.

PMID- 30225152
TI  - Venetoclax in Combination with Decitabine for Relapsed T-Cell Acute Lymphoblastic
      Leukemia after Allogeneic Hematopoietic Cell Transplant.
AB  - Long-term disease-free survival in adults with T-cell acute lymphoblastic
      leukemia (T-ALL) remains poor, particularly after relapse, with few available
      salvage options. Preclinical data suggest that inhibition of the antiapoptotic
      protein BCL-2 (B-cell lymphoma 2) either alone or in combination with other
      agents, may be a unique therapeutic approach for the treatment of T-ALL. We
      present a case of a young male with T-ALL, relapsed after allogeneic
      hematopoietic stem cell transplant, who achieved a second complete remission
      following salvage therapy with combined venetoclax and decitabine. Assessment of
      measurable residual disease by next generation sequencing showed no evidence of
      residual disease of a sensitivity of 1 * 10-6. While the combination of
      venetoclax and hypomethylating agents has shown promise in the treatment of
      relapsed/refractory AML, and to our knowledge, this is the first report of this
      combination demonstrating clinical activity in relapsed/refractory T-ALL.

PMID- 30225153
TI  - Anti-CD20 Treatment of Autoimmune Hemolytic Anemia Refractory to Corticosteroids
      and Azathioprine: A Pediatric Case Report and Mini Review.
AB  - Autoimmune hemolytic anemia (AIHA) is a relatively uncommon hematological entity
      in children and sometimes is characterized by a severe course requiring more than
      one line course therapy. Treatment decisions depend on the severity and
      chronicity of the anemia and the characteristics of the autoantibodies.
      Immunosuppression with corticosteroids is the first-line treatment, especially in
      warm-reactive AIHA. Refractory cases are treated with immunosuppressive drugs,
      cytotoxic agents, androgens, or splenectomy, with various side effects and
      questionable efficacy. Another second-line option is rituximab, an anti-CD20
      monoclonal antibody, which has been used as an off-label agent with encouraging
      results from small limited studies or case reports. Herein, we add our experience
      on the safety and clinical efficacy of rituximab by presenting the case of a boy
      with warm-type AIHA resistant to corticosteroids and azathioprine, successfully
      treated with rituximab. We also offer a review of the relevant literature.

PMID- 30225155
TI  - Second Trimester Cervical Ectopic Pregnancy and Hemorrhage: A Case Report and
      Review of the Literature.
AB  - Cervical ectopic pregnancies are a rare occurrence in the United States. Here we
      present the interdisciplinary and conservative management approach to a cervical
      ectopic at an advanced gestational age. In addition, we review the surgical
      management of hemorrhage from cervical ectopic pregnancies, which is often
      catastrophic and life-threatening.

PMID- 30225154
TI  - Meningococcal Pneumonia in a Young Healthy Male.
AB  - A 23-year-old male presented to the emergency department with one-day history of
      right-sided pleuritic chest pain, haemoptysis, and fever. In the emergency
      department, the blood pressure was 140/60 mmHg, heart rate 89/min, body
      temperature 40 degrees C, respiratory rates 20 breaths/min, and oxygen saturation
      98% in room air. Physical examination revealed rales and bronchial breathing in
      the right infrascapular region. Laboratory analysis showed raised white blood
      cell counts and elevated inflammation markers. Chest X-ray showed right lower
      lobe consolidation. Intravenous(IV) ceftriaxone and doxycycline were started for
      the management of community-acquired pneumonia as per the local guideline. Later,
      on admission, blood culture was positive for Neisseria meningitidis (N.
      meningitidis). Ceftriaxone was continued for 4 days, and the patient was
      discharged while being on oral amoxicillin (1 gm TDS) for another 3 days. He
      remained well during the outpatient follow-up.

PMID- 30225156
TI  - Tocilizumab for the Treatment of Mevalonate Kinase Deficiency.
AB  - Mevalonate kinase deficiency (MKD) is a severe autoinflammatory disease caused by
      recessive mutations in MVK resulting in reduced function of the enzyme mevalonate
      kinase, involved in the cholesterol/isoprenoid pathway. MKD presents with
      periodic episodes of severe systemic inflammation, poor quality of life, and life
      threatening sequelae if inadequately treated. We report the case of a 12-year-old
      girl with MKD and severe autoinflammation that was resistant to IL-1 and TNF
      alpha blockade. In view of this, she commenced intravenous tocilizumab (8 mg/kg
      every 2 weeks), a humanised monoclonal antibody targeting the IL-6 receptor (IL
      6R) that binds to membrane and soluble IL-6R, inhibiting IL-6-mediated signaling.
      She reported immediate cessation of fever and marked improvement in her energy
      levels following the first infusion; after the fifth dose, she was in complete
      clinical and serological remission, now sustained for 24 months. This is one of
      the first reported cases of a child with MKD treated successfully with
      tocilizumab and adds to the very limited experience of this treatment for MKD. IL
      6 blockade could therefore be an important addition to the armamentarium for the
      treatment of this rare monogenic autoinflammatory disease.

PMID- 30225157
TI  - Gender Norms, Violence in Childhood, and Men's Coercive Control in Marriage: A
      Multilevel Analysis of Young Men in Bangladesh.
AB  - Objective: Coercive control in marriage is common in patriarchal settings, but
      multilevel determinants are understudied. Method: Using a probability sample of
      570 junior men (married, 18-34 years) from the Bangladesh survey of the 2011 UN
      Multi-Country Study of Men and Violence, we examined how exposure to violence in
      childhood and community-level gender norms were related to men's attitudes about
      gender equity and use of controlling behavior. We tested whether community-level
      gender norms moderated the relationship between men's exposure to violence in
      childhood and our outcomes. Results: According to results from multilevel Poisson
      regression models, as community gender norms become more equitable by 1 standard
      deviation, a junior married man's expected rate of controlling behavior is lower
      by 0.11, and his rate of agreement with gender equitable attitudes is higher by
      0.27. More gender-equitable community norms were negatively related to a junior
      married man's use of controlling behavior. Childhood exposure to violence was not
      associated with use of controlling behavior. There was a significant cross-level
      interaction such that exposure to violence had a stronger negative impact on
      men's gender equitable attitudes in communities with lower overall gender equity
      than those with higher overall gender equity. The corresponding cross-level
      interaction effect was not significant for the controlling behavior outcome.
      Conclusions: More equitable community gender norms may encourage more gender
      equitable attitudes and discourage use of controlling behavior among junior men,
      suggesting that interventions to change community gender norms may reduce
      coercive control of women in marriage.

PMID- 30225158
TI  - Translational Retinal Research and Therapies.
AB  - The following review summarizes the state of the art in representative aspects of
      gene therapy/translational medicine and evolves from a symposium held at the
      School of Veterinary Medicine, University of Pennsylvania on November 16, 2017
      honoring Dr. Gustavo Aguirre, recipient of ARVO's 2017 Proctor Medal. Focusing on
      the retina, speakers highlighted current work on moving therapies for inherited
      retinal degenerative diseases from the laboratory bench to the clinic.

PMID- 30225159
TI  - TNFRSF10C methylation is a new epigenetic biomarker for colorectal cancer.
AB  - Background: Abnormal methylation of TNFRSF10C was found to be associated with
      different types of cancers, excluding colorectal cancer (CRC). In this paper, the
      performance of TNFRSF10C methylation in CRC was studied in two stages. Method:
      The discovery stage was involved with 38 pairs of CRC tumor and paired adjacent
      non-tumor tissues, and 69 pairs of CRC tumor and paired adjacent non-tumor
      tissues were used for the validation stage. Quantitative methylation specific PCR
      (qMSP) method and percentage of methylated reference (PMR) were used to test and
      represent the methylation level of TNFRSF10C, respectively. A dual-luciferase
      reporter gene experiment was conducted to evaluate the promoter activity of
      TNFRSF10C fragment. Results: A significant association of TNFRSF10C promoter
      hypermethylation with CRC was found and validated (discovery stage: 24.67 +/-
      7.52 vs. 3.36 +/- 0.89; P = 0.003; validation stage: 31.21 +/- 12.48 vs. 4.52 +/-
      1.47; P = 0.0005). Subsequent analyses of TCGA data among 46 pairs of CRC samples
      further confirmed our findings (cg23965061: P = 4E - 6; cg14015044: P = 1E - 7).
      Dual-luciferase reporter gene assay revealed that TNFRSF10C fragment was able to
      significantly promote gene expression (Fold change = 2.375, P = 0.013). Our data
      confirmed that TNFRSF10C promoter hypermethylation can predict shorter overall
      survival of CRC patients (P = 0.032). Additionally, bioinformatics analyses
      indicated that TNFRSF10C hypermethylation was significantly associated with lower
      TNFRSF10C expression. Conclusion: Our work suggested that TNFRSF10C
      hypermethylation was significantly associated with the risk of CRC.

PMID- 30225160
TI  - Multielement analysis of plant extracts with potential use in the treatment of
      peptic ulcers by synchrotron radiation total reflection X-ray fluorescence.
AB  - Some plants popularly employed for the treatment of peptic ulcers have proved to
      be attractive sources of new drugs. Despite extensive research, the
      pharmacological and toxicological potentials of these plants are not fully
      understood. In this context, the aim of this work was to analyze the
      multielemental composition of the methanolic extracts of three of those plants,
      Alchornea glandulosa (AG), Davilla elliptica (DE) and Davilla nitida (DN), with
      the intention of contributing to the understanding of the mechanisms of action of
      these extracts. For this purpose, we used the analytical technique of total
      reflection X-ray fluorescence (TXRF) by synchrotron radiation at the Brazilian
      Synchrotron Light Source (LNLS/CNPEM). It was possible to determine the
      concentrations of the elements: P, S, Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, Rb
      and Br in all of the samples. Selenium (Se) was detected only in the DN extract.
      An inverse relationship between the concentrations of elements with proven
      effectiveness and the gastroprotective activity of extracts considering induction
      protocols with ethanol and non-steroidal anti-inflammatory drugs (NSAIDs) was
      obtained. This data suggests that the function of the extract is not only
      associated with providing the elements for restoring the gastric mucosa but that
      it also promotes the displacement of these elements from other parts of the
      mucosa to the damaged area. Correlations between the concentrations of the
      elements were also obtained. In the DE extract, which is the most effective
      extract for both induction protocols, the obtained correlations were above 70%
      among almost all of the elements, and no anticorrelations were found. For the
      other two extracts, in the less effective extract (AG) anticorrelations above 70%
      were predominantly found. Meanwhile, in the DN extract, a few high
      anticorrelations were found, which may explain its intermediate stage of
      effectiveness.

PMID- 30225161
TI  - Trust and distrust in information systems at the workplace.
AB  - Digitalization of work processes is advancing, and this is increasingly supported
      by complex information systems (IS). However, whether such systems are used by
      employees largely depends on users' trust in these IS. Because there are few
      systematic studies on this topic, this research provides an initial exploration
      and validation of preconditions for trust in work-related IS. In Study 1, N = 30
      professionals were asked to describe occupational incidents in which they had
      highly trusted or distrusted an IS. Content analysis of 111 critical incidents
      described in the in-depth interviews led to 12 predictors of trust and distrust
      in IS, which partly correspond to the structure of the established IS success
      model (Delone & McLean, 2003) but also exceed this structure. The resulting
      integrative model of trust in IS at work was validated in Study 2 using an online
      questionnaire with N = 179 professionals. Based on regression analyses,
      reliability (system quality) and credibility (information quality) of IS were
      identified as the most important predictors for both trust and distrust in IS at
      work. Contrasting analyses revealed diverging qualities of trust and distrust in
      IS : whereas well-being and performance were rated higher in trust events,
      experienced strain was rated higher in distrust events. Together, this study
      offers a first comprehensive model of trust in IS at work based on systematic
      empirical research. In addition to implications for theory advancement, we
      suggest practical implications for how to support trust and to avoid distrust in
      IS at work.

PMID- 30225162
TI  - Antiviral therapy effectively improves liver hemodynamics as evidenced by serum
      biomarker and contrast-enhanced ultrasound examinations in patients with
      hepatitis B cirrhosis.
AB  - Background and Aims: To prospectively evaluate the effects of antiviral therapy
      on liver hemodynamics in patients with hepatitis B cirrhosis. Methods: Seventy
      consecutive eligible HBV-related cirrhotic inpatients were enrolled in the
      prospective study. Fifty-two received different nucleoside analogs monotherapy
      and 18 denied antiviral therapy. Their liver biochemistry profiles and HBV-DNA
      were measured at the baseline and every 3 months. Peripheral blood vWF and
      sCD163, as well as liver ultrasound Doppler parameters including portal vein
      diameter (PVD), portal vein velocity (PVV), portal vein congestion index (PV-CI),
      hepatic vein damping index (HV-DI), hepatic arterial arrival time (HAAT), hepatic
      vein arrival time (HVAT) and intrahepatic cycle time (HV-HA), were measured at
      the baseline and the follow-up periods. Results: In the antiviral group, all
      patients achieved complete virologic and liver biochemical responses after 3
      month antiviral treatment. Furthermore, the response states were maintained till
      the follow-up endpoint. However, in the non-antiviral group, HBV DNA replication
      resulted in higher levels of ALT and AST compared to the baseline values (P <
      0.05). In the antiviral group, PVD, PV-CI, HV-DI, vWF-Ag and sCD163 were all
      significantly reduced than the baseline values (P < 0.05), and PVV was
      significantly increased than the baseline value (P < 0.05). Conclusions:
      Antiviral therapy could effectively suppress hepatocyte inflammation and
      alleviate the dysfunction of intrahepatic vascular endothelial and hepatic
      macrophages, which might improve hepatic hemodynamic function in HBV-related
      cirrhosis.

PMID- 30225163
TI  - The ability of magnetic field sensors to monitor feeding in three domestic
      herbivores.
AB  - The rate at which animals ingest food is a fundamental part of animal ecology
      although it is rarely quantified, with recently-developed animal-attached tags
      providing a potentially viable approach. However, to date, these methods lack
      clarity in differentiating various eating behaviours, such as 'chewing' from
      'biting'. The aims of this study were to examine the use of inter-mandibular
      angle sensors (IMASENs), to quantify grazing behaviour in herbivores including
      cattle (Bos taurus), sheep (Ovis aries) and pygmy goats (Capra aegagrus hircus)
      eating different foodstuffs. Specifically, we aimed to: (1) quantify jaw
      movements of each species and determine differences between biting and chewing;
      (2) assess whether different food types can be discerned from jaw movements; and
      (3) determine whether species-specific differences in jaw movements can be
      detected. Subjects were filmed while consuming concentrate, hay, grass and browse
      to allow comparison of observed and IMASEN-recorded jaw movements. This study
      shows that IMASENs can accurately detect jaw movements of feeding herbivores,
      and, based on the rate of jaw movements, can classify biting (taking new material
      into the mouth) from chewing (masticating material already in the mouth). The
      biting behaviours associated with concentrate pellets could be identified easily
      as these occurred at the fastest rate for all species. However, the rates of
      chewing different food items were more difficult to discern from one another.
      Comparison of chew:bite ratios of the various food types eaten by each species
      showed no differences. Species differences could be identified using bite and
      chew rates. Cattle consistently displayed slower bite and chew rates to sheep and
      pygmy goats when feeding, while sheep and pygmy goats showed similar bite and
      chew rates when feeding on concentrate pellets. Species-specific differences in
      chew:bite ratios were not identified. Magnetometry has the potential to record
      quantitative aspects of foraging such as the feeding duration, food handling time
      and food type. This is of major importance for researchers interested in both
      captive (e.g., agricultural productivity) and wild animal foraging dynamics as it
      can provide quantitative data with minimal observer interference.

PMID- 30225164
TI  - The impact of chemerin or chemokine-like receptor 1 loss on the mouse gut
      microbiome.
AB  - Chemerin is an adipocyte derived signalling molecule (adipokine) that serves as a
      ligand activator of Chemokine-like receptor 1(CMKLR1). Chemerin/CMKLR1 signalling
      is well established to regulate fundamental processes in metabolism and
      inflammation. The composition and function of gut microbiota has also been shown
      to impact the development of metabolic and inflammatory diseases such as obesity,
      diabetes and inflammatory bowel disease. In this study, we assessed the
      microbiome composition of fecal samples isolated from wildtype, chemerin, or
      CMKLR1 knockout mice using Illumina-based sequencing. Moreover, the knockout mice
      and respective wildtype mice used in this study were housed at different
      universities allowing us to compare facility-dependent effects on microbiome
      composition. While there was no difference in alpha diversity within samples when
      compared by either facility or genotype, we observed a dramatic difference in the
      presence and abundance of numerous taxa between facilities. There were minor
      differences in bacterial abundance between wildtype and chemerin knockout mice,
      but significantly more differences in taxa abundance between wildtype and CMKLR1
      knockout mice. Specifically, CMKLR1 knockout mice exhibited decreased abundance
      of Akkermansia and Prevotella, which correlated with body weight in CMKLR1
      knockout, but not wildtype mice. This is the first study to investigate a linkage
      between chemerin/CMKLR1 signaling and microbiome composition. The results of our
      study suggest that chemerin/CMKLR1 signaling influences metabolic processes
      through effects on the gut microbiome. Furthermore, the dramatic difference in
      microbiome composition between facilities might contribute to discrepancies in
      the metabolic phenotype of CMKLR1 knockout mice reported by independent groups.
      Considered altogether, these findings establish a foundation for future studies
      to investigate the relationship between chemerin signaling and the gut microbiome
      on the development and progression of metabolic and inflammatory disease.

PMID- 30225165
TI  - Deep divergence of Red-crowned Ant Tanager (Habia rubica: Cardinalidae), a
      multilocus phylogenetic analysis with emphasis in Mesoamerica.
AB  - Many neotropical species have a complex history of diversification as a result of
      the influence of geographical, ecological, climatic, and geological factors that
      determine the distribution of populations within a lineage. Phylogeography
      identifies such populations, determines their geographic distributions, and
      quantifies the degree of genetic divergence. In this work we explored the genetic
      structure of Habia rubica populations, a polytypic taxon with 17 subspecies
      described, in order to obtain hypotheses about their evolutionary history and
      processes of diversification. We undertook multilocus analyses using sequences of
      five molecular markers (ND2, ACOI-I9, MUSK, FGB-I5 and ODC), and sampling from
      across the species' distribution range, an area encompassing from Central Mexico
      throughout much of South America. With these data, we obtained a robust
      phylogenetic hypothesis, a species delimitation analysis, and estimates of
      divergence times for these lineages. The phylogenetic hypothesis of concatenated
      molecular markers shows that H. rubica can be divided in three main clades: the
      first includes Mexican Pacific coast populations, the second is formed by
      population from east of Mexico to Panama and the third comprises the South
      American populations. Within these clades we recognize seven principal
      phylogroups whose limits have a clear correspondence with important geographical
      discontinuities including the Isthmus of Tehuantepec in southern Mexico, the
      Talamanca Cordillera, and the Isthmus of Panama in North America. In South
      America, we observed a marked separation of two phylogroups that include the
      populations that inhabit mesic forests in western and central South America
      (Amazon Forest) and those inhabiting the seasonal forest from the eastern and
      northern regions of the South America (Atlantic Forest). These areas are
      separated by an intervening dry vegetation "diagonal" (Chaco, Cerrado and
      Caatinga). The geographic and genetic structure of these phylogroups describes a
      history of diversification more active and complex in the northern distribution
      of this species, producing at least seven well-supported lineages that could be
      considered species.

PMID- 30225166
TI  - An overview report on the application of heteropoly acids on supporting materials
      in the photocatalytic degradation of organic pollutants from aqueous solutions.
AB  - Organic pollutants contaminate water resources and the environment when
      discharged into water streams. Also, the presence of these materials in
      incompletely treated or untreated wastewater leads to serious environmental
      hazards. The hydroxyl radicals and holes are regarded as the most oxidant species
      in the degradation of organic pollutants using the studied composites. The
      results of this review show that heteropoly acids on supporting materials could
      be considered as appropriate photocatalysts in the removal of organic pollutant
      from aqueous solutions.

PMID- 30225167
TI  - Effects of macroalgae loss in an Antarctic marine food web: applying extinction
      thresholds to food web studies.
AB  - Antarctica is seriously affected by climate change, particularly at the Western
      Antarctic Peninsula (WAP) where a rapid regional warming is observed. Potter Cove
      is a WAP fjord at Shetland Islands that constitutes a biodiversity hotspot where
      over the last years, Potter Cove annual air temperatures averages increased by
      0.66  degrees C, coastal glaciers declined, and suspended particulate matter
      increased due to ice melting. Macroalgae are the main energy source for all
      consumers and detritivores of Potter Cove. Some effects of climate change favor
      pioneer macroalgae species that exploit new ice-free areas and can also decline
      rates of photosynthesis and intensify competition between species due to the
      increase of suspended particulate matter. In this study, we evaluated possible
      consequences of climate change at Potter Cove food web by simulating the
      extinction of macroalgae and detritus using a topological approach with
      thresholds of extinction. Thresholds represent the minimum number of incoming
      links necessary for species' survival. When we simulated the extinctions of
      macroalgae species at random, a threshold of extinction beyond 50% was necessary
      to obtain a significant number of secondary extinctions, while with a 75%
      threshold a real collapse of the food web occurred. Our results indicate that
      Potter Cove food web is relative robust to macroalgae extinction. This is
      dramatically different from what has been found in other food webs, where the
      reduction of 10% in prey intake caused a disproportionate increase of secondary
      extinctions. Robustness of the Potter Cove food web was mediated by omnivory and
      redundancy, which had an important relevance in this food web. When we eliminated
      larger-biomass species more secondary extinctions occurred, a similar response
      was observed when more connected species were deleted, yet there was no
      correlation between species of larger-biomass and high-degree. This similarity
      could be explained because both criteria involved key species that produced an
      emerging effect on the food web. In this way, large-biomass and high-degree
      species could be acting as source for species with few trophic interactions or
      low redundancy. Based on this work, we expect the Potter Cove food web to be
      robust to changes in macroalgae species caused by climate change until a high
      threshold of stress is reached, and then negative effects are expected to spread
      through the entire food web leading to its collapse.

PMID- 30225168
TI  - Autonomic dysfunction and white matter microstructural changes in drug-naive
      patients with Parkinson's disease.
AB  - Background: Autonomic dysfunction (AD) is one of the non-motor features of
      Parkinson's disease (PD). Some symptoms tend to occur in the early stages of PD.
      AD also has a great impact on patient's quality of life. In this study, we aimed
      to discover the association between AD (Scales for Outcomes in Parkinson's
      disease-Autonomic, SCOPA-AUT) and microstructural changes in white matter tracts
      in drug-naive early PD patients to elucidate the central effects of autonomic
      nervous system impairments. Method: In total, this study included 85 subjects
      with PD recruited from the Parkinson's Progression Markers Initiative (PPMI)
      database. Among the 85 PD patients, 38 were in Hoehn & Yahr stage 1 (HY1PD) and
      47 were in stage 2 (HY2PD). Diffusion magnetic resonance imaging (DMRI) data were
      reconstructed in the MNI space using q-space diffeomorphic reconstruction to
      obtain the spin distribution function. The spin distribution function (SDF)
      values were used in DMRI connectometry analysis. We investigated through
      diffusion MRI connectometry the structural correlates of white matter tracts with
      SCOPA-AUT subscores and total score. Results: Connectometry analysis also
      revealed positive association with white matter density in bilateral
      corticospinal tract in HY1PD patients and negative association in genu of corpus
      callosum (CC) and, bilateral cingulum in both groups. In addition, there were
      associations between gastrointestinal, sexual, thermoregulatory and urinary items
      and structural brain connectivity in PD. Conclusion: Our study reveals positive
      correlation, suggesting neural compensations in early PD. Cingulum and CC tracts
      have well-known roles in PD pathology, compatible with our findings that bring
      new insights to specific areas of AD and its role in central nervous system (CNS)
      neurodegeneration, paving the way for using prodromal makers in the diagnosis and
      treatment of PD.

PMID- 30225169
TI  - Interaction of guidance types and the Need for Cognitive Closure in wiki-based
      learning.
AB  - One purpose of wikis is the collaborative generation of content. During creation
      processes, controversies between authors emerge that they discuss on the
      article's talk page. Research suggests that controversies based on opposing
      points of view and contradictory evidence can be fruitful to trigger individual
      elaboration processes. However, previous research also showed that many wikis are
      not necessarily suited to identify relevant discussion contents and thus users
      need additional support as guidance. In an experimental laboratory study (N =
      181) on wiki talk pages, we investigated two guidance measures in conjunction
      with the need for cognitive closure: (1) visual markers to highlight controversy
      status (implicit guidance) and (2) a collaboration script that directs users
      towards discussions (explicit guidance). Effects on wiki processes and learning
      outcomes were analysed. The results show that both guidance types can affect user
      behaviours, but in interaction with the individual Need for Cognitive Closure
      there were no meaningful effects. With respect to learning outcomes, we found an
      anticipated pattern for the interaction of the Need for Cognitive Closure with
      both guidance principles. The data provides support for differences in the
      learning success depending on the provided guidance type and the individual Need
      for Cognitive Closure.

PMID- 30225170
TI  - Balanced and positively worded personality short-forms: Mini-IPIP validity and
      cross-cultural invariance.
AB  - Background: The Mini-IPIP scales (Donellan et al., 2006) are possibly one of the
      most commonly used short inventories for measuring the Big Five Factors of
      personality. In this study, we aimed to investigate the psychometric properties
      of two Mini-IPIP Spanish short forms, one balanced and one positively wording
      (PW). Method: Two samples, one from native Spanish speakers and another from
      native English speakers, made up a total of 940 participants in this study. The
      short forms were translated and adapted based on international guidelines.
      Reliability (internal and composite) and validity analyses (construct ESEM,
      concurrent, predictive and cross-cultural invariance through multi-group
      factorial models) were performed. Results: For both the balanced scale and the PW
      one, modeling a method factor was not relevant. The reliability and validity
      indices of both forms were according to theory and prior studies' findings: (a)
      personality factors were medium-high related to affective factors; (b)
      personality factors were less related to life satisfaction than affective
      factors; (c) life satisfaction was medium-high related to affective factors; (d)
      neuroticism appeared mainly related to all criteria variables; and (e) an
      acceptable level of invariance was achieved with regard to the English version.
      Discussion: This study contributes to research on personality assessment by
      providing the first evidence regarding the psychometric properties of a PW short
      measure. These results suggest that PW short scales of personality used after
      data screening techniques may be appropriate for future studies (e.g., cross
      cultural, content validity).

PMID- 30225171
TI  - Children are not like other loads: a cross-cultural perspective on the influence
      of burdens and companionship on human walking.
AB  - A major portion of humans' activity-based energy expenditure is taken up by
      locomotion, particularly walking. Walking behaviors have energetic outcomes and
      as such can be important windows into how populations and groups adjust to
      different environmental and task constraints. While sex differences in the speed
      of paired walkers have been established by others, the dynamics of how walkers
      adjust their speed in more varied groups and in groups containing children
      remains unexplored. Furthermore, little ecological data exists to illustrate the
      relationships between walking speed and child-carrying. Here, we aim to determine
      how culture impacts the effects of group composition and infant-carrying on
      walking speed. Because the determinants of group dynamics and parental investment
      are partially cultural, we examine walking behavior in the Northwestern United
      States and in Central Uganda. Using an observational method, we recorded the
      speed, load carriage, and group composition of pedestrians in a single
      naturalistic urban environment within each country. Our data suggest that
      children are treated fundamentally differently than other loads or the presence
      of walking partners, and that major speed adjustments are child-dependent. Our
      data furthermore indicate that Ugandans walk more slowly in groups than when
      alone, while Americans walk more quickly in groups. Clear distinctions between
      the groups make large generalizations about walking behavior difficult, and
      highlight the importance of culturally specific contexts.

PMID- 30225172
TI  - A close relative of the Amazon river dolphin in marine deposits: a new Iniidae
      from the late Miocene of Angola.
AB  - Background: A few odontocetes (echolocating toothed cetaceans) have been able to
      independently colonize freshwater ecosystems. Although some extant species of
      delphinids (true dolphins) and phocoenids (porpoises) at least occasionally
      migrate upstream of large river systems, they have close relatives in fully
      marine regions. This contrasts with the three odontocete families only containing
      extant species with a strictly freshwater habitat (Iniidae in South America, the
      recently extinct Lipotidae in China, and Platanistidae in southeast Asia). Among
      those, the fossil record of Iniidae includes taxa from freshwater deposits of
      South America, partly overlapping geographically with the extant Amazon river
      dolphin Inia geoffrensis, whereas a few marine species from the Americas were
      only tentatively referred to the family, leaving the transition from a marine to
      freshwater environment poorly understood. Methods: Based on a partial odontocete
      skeleton including the cranium, discovered in late Miocene (Tortonian-Messinian)
      marine deposits near the estuary of the Cuanza River, Angola, we describe a new
      large iniid genus and species. The new taxon is compared to other extinct and
      extant iniids, and its phylogenetic relationships with the latter are
      investigated through cladistic analysis. Results and Discussion: The new genus
      and species Kwanzacetus khoisani shares a series of morphological features with
      Inia geoffrensis, including the combination of a frontal boss with nasals being
      lower on the anterior wall of the vertex, the laterally directed postorbital
      process of the frontal, the anteroposterior thickening of the nuchal crest, and
      robust teeth with wrinkled enamel. As confirmed (although with a low support)
      with the phylogenetic analysis, this makes the new taxon the closest relative of
      I. geoffrensis found in marine deposits. The geographic provenance of K.
      khoisani, on the eastern coast of South Atlantic, suggests that the transition
      from the marine environment to a freshwater, Amazonian habitat may have occurred
      on the Atlantic side of South America. This new record further increases the
      inioid diversity during the late Miocene, a time interval confirmed here as the
      heyday for this superfamily. Finally, this first description of a Neogene
      cetacean from inland deposits of western sub-Saharan Africa reveals the potential
      of this large coastal area for deciphering key steps of the evolutionary history
      of modern cetaceans in the South Atlantic.

PMID- 30225173
TI  - Differential expression of NF-kappaB heterodimer RelA/p50 in human urothelial
      carcinoma.
AB  - Background: Urothelial carcinoma (UC) is the fifth most common malignancy that
      accounts for 5% of all cancers. Diagnostic markers that predict UC progressions
      are inadequate. NF-kappaB contributes towards disease progression upon
      constitutive activation in many solid tumors. The nuclear localization of NF
      kappaB indicates increased transcriptional activity while cytoplasmic
      localization indicates the inactive protein repository that can be utilized
      readily by a malignant cell. This study delineates the nuclear and cytoplasmic
      differential expression of NF-kappaB heterodimers in UC progression. Methods: The
      involvement of the NF-kappaB proteins in UC was analyzed in silico using
      cytoscape. The expression of NF-kappaB heterodimers was analyzed by
      immunohistochemistry. Results: PINA4MS app in cytoscape revealed over expression
      of RelA and suppression of NF-kappaB1 (p50 precursor) in UC whereas the
      expression of NF-kappaB target proteins remained unhindered. Immunohistochemical
      localization showed nuclear RelA/p50 in low grade UC whereas in high grade only
      RelA expression was observed. Conversely, cytoplasmic expression of RelA/p50
      remained extensive across high and low grade UC tissues (p < 0.005). RelA nuclear
      and cytoplasmic expression (p < 0.005) was directly proportional to the disease
      progression. In our study, some of the high-grade UC tissues with squamous
      differentiation and muscle invasion had extensive nuclear p50 localization. The
      phenomenon of RelA/p50 expression seen increased in low-grade UC than high grade
      UC might be due to their interaction with other members of NF-kappaB family of
      proteins. Thus, NF-kappaB RelA/p50 differential expression may play a unique role
      in UC pathogenesis and can serve as a biomarker for diagnosis.

PMID- 30225174
TI  - Cytokine and microRNA levels during different periods of paradoxical sleep
      deprivation and sleep recovery in rats.
AB  - Background: Sleep has a fundamental role in the regulation of homeostasis. The
      aim of this study was to assess the effect of different periods of paradoxical
      sleep deprivation (PSD) and recovery on serum levels of cytokines and miRNAs
      related to inflammatory responses. Methods: Male Wistar rats were submitted to a
      PSD of 24, 96, or 192 h, or of 192 h followed by 20 days of recovery (192 h
      PSD+R). The concentrations of corticosterone, cytokines (IL-6, TNF, IL-10,
      Adiponectin) and miRNAs (miR-146a, miR-155, miR-223, miR-16, miR-126, miR-21) in
      serum were evaluated. Results: At PSD 24 h a significant increase of IL-6 and
      decrease of IL-10 were observed. At PSD 96h adiponectin increased. At 192 h of
      PSD IL-6 increased significantly again, accompanied by a threefold increase of IL
      10 and an increase of serum corticosterone. After 20 days of recovery (192 h
      PSD+R) corticosterone, IL-6 and TNF levels increased significantly, while IL-10
      decreased also significantly. Regarding the miRNAs at 24 h of PSD serum miR-146a,
      miR-155, miR-223, and miR-16 levels all increased. At 96 h of PSD miR-223
      decreased. At 192 h of PSD decreases in miR-16 and miR-126 were observed. After
      recovery serum miR-21 increased and miR-16 decreased. Conclusion: PSD induces a
      dynamic response likely reflecting the induced cellular stress and manifested as
      variating hormonal and inflammatory responses. Sleep deprivation disturbed
      corticosterone, cytokine and miRNA levels in serum related to the duration of
      sleep deprivation, as short-term PSD produced effects similar to those of an
      acute inflammatory response and long-term PSD induced long-lasting disturbances
      of biological mediators.

PMID- 30225175
TI  - An integrative and citizen science based approach to the rediscovery and
      redescription of the only known high-altitude endemic Pill Millipede, Glomeris
      aurita Koch (Diplopoda, Glomerida).
AB  - The pill millipede species Glomeris aurita Koch, 1847 remained of relative
      unknown origin and appearance until its recent rediscovery in samples from the
      Bergamasque Alps, northern Italy. In order to provide an integrative
      redescription and accurate identification of the high-altitude microendemic G.
      aurita, COI barcode sequences from three individuals coming from two different
      localities were obtained. These sequences are compared with those of the syntopic
      endemic G. oblongoguttata Verhoeff, 1894, the widespread black morph of G. romana
      Verhoeff, 1900, as well as several widespread species including G. marginata
      Villers, 1789, G. connexa Koch, 1847, and G. klugii Brandt, 1833, which have rare
      colour morphs that exhibit some similarity to G. aurita. To rule-out any identity
      confusion of G. aurita with other high-altitude or little-known Italian Glomeris,
      specimens of G. transalpina Koch, 1836, G. oropensis Verhoeff, 1934, and G.
      primordialis Verhoeff, 1932 were also added to the dataset. Altogether, 24
      sequences were compared. Morphologically, the specimens of G. aurita were studied
      utilizing scanning electron microscopy as well as non-invasive micro-CT
      technology. The distribution of both Bergamasque endemics, G. aurita and G.
      oblongoguttata, could be mapped and compared utilizing samples from the Museo
      civico di Scienze Naturali di Bergamo, as well as photographic evidence from an
      Italian naturalist forum. G. aurita has a very short active period and is the
      first known pill millipede species restricted to mountain tops and cold places,
      possibly representing a Nunatak survivor.

PMID- 30225176
TI  - Assessment of the bacterial community structure in shallow and deep sediments of
      the Perdido Fold Belt region in the Gulf of Mexico.
AB  - The Mexican region of the Perdido Fold Belt (PFB), in northwestern Gulf of Mexico
      (GoM), is a geological province with important oil reservoirs that will be
      subjected to forthcoming oil exploration and extraction activities. To date,
      little is known about the native microbial communities of this region, and how
      these change relative to water depth. In this study we assessed the bacterial
      community structure of surficial sediments by high-throughput sequencing of the
      16S rRNA gene at 11 sites in the PFB, along a water column depth gradient from 20
      to 3,700 m, including five shallow (20-600 m) and six deep (2,800-3,700 m)
      samples. The results indicated that OTUs richness and diversity were higher for
      shallow sites (OTUs = 2,888.2 +/- 567.88; H' = 9.6 +/- 0.85) than for deep sites
      (OTUs = 1,884.7 +/- 464.2; H' = 7.74 +/- 1.02). Nonmetric multidimensional
      scaling (NMDS) ordination revealed that shallow microbial communities grouped
      separately from deep samples. Additionally, the shallow sites plotted further
      from each other on the NMDS whereas samples from the deeper sites (abyssal
      plains) plotted much more closely to each other. These differences were related
      to depth, redox potential, sulfur concentration, and grain size (lime and clay),
      based on the environmental variables fitted with the axis of the NMDS ordination.
      In addition, differential abundance analysis identified 147 OTUs with significant
      fold changes among the zones (107 from shallow and 40 from deep sites), which
      constituted 10 to 40% of the total relative abundances of the microbial
      communities. The most abundant OTUs with significant fold changes in shallow
      samples corresponded to Kordiimonadales, Rhodospirillales, Desulfobacterales
      (Desulfococcus), Syntrophobacterales and Nitrospirales (GOUTA 19, BD2-6, LCP-6),
      whilst Chromatiales, Oceanospirillales (Amphritea, Alcanivorax), Methylococcales,
      Flavobacteriales, Alteromonadales (Shewanella, ZD0117) and Rhodobacterales were
      the better represented taxa in deep samples. Several of the OTUs detected in both
      deep and shallow sites have been previously related to hydrocarbons consumption.
      Thus, this metabolism seems to be well represented in the studied sites, and it
      could abate future hydrocarbon contamination in this ecosystem. The results
      presented herein, along with biological and physicochemical data, constitute an
      available reference for further monitoring of the bacterial communities in this
      economically important region in the GoM.

PMID- 30225177
TI  - Explanation of observational data engenders a causal belief about smoking and
      cancer.
AB  - Most researchers do not deliberately claim causal results in an observational
      study. But do we lead our readers to draw a causal conclusion unintentionally by
      explaining why significant correlations and relationships may exist? Here we
      perform a randomized controlled experiment in a massive open online course run in
      2013 that teaches data analysis concepts to test the hypothesis that explaining
      an analysis will lead readers to interpret an inferential analysis as causal. We
      test this hypothesis with a single example of an observational study on the
      relationship between smoking and cancer. We show that adding an explanation to
      the description of an inferential analysis leads to a 15.2% increase in readers
      interpreting the analysis as causal (95% confidence interval for difference in
      two proportions: 12.8%-17.5%). We then replicate this finding in a second large
      scale massive open online course. Nearly every scientific study, regardless of
      the study design, includes an explanation for observed effects. Our results
      suggest that these explanations may be misleading to the audience of these data
      analyses and that qualification of explanations could be a useful avenue of
      exploration in future research to counteract the problem. Our results invite many
      opportunities for further research to broaden the scope of these findings beyond
      the single smoking-cancer example examined here.

PMID- 30225178
TI  - Mass fluctuation in breeding females, males, and helpers of the Florida scrub-jay
      Aphelocoma coerulescens.
AB  - Much evidence suggests that birds actively regulate their body mass reserves
      relative to their energy needs. Energy requirements during reproduction may
      differ in relation to sex-specific behavioural roles or, in the case of
      cooperative breeders, breeders relative to helpers. We measured body mass of free
      living Florida scrub-jays throughout the nesting season by training them to land
      on an electronic balance. Jays exhibited a pattern of diurnal linear mass gain,
      from morning to afternoon. Day-to-day mass fluctuations, defined as the
      difference between mass on two consecutive days, were small (>80% were within 2
      g, less than 3% of the mass of an adult bird) for all classes of jays: female
      breeders, male breeders and prebreeding helpers. The jays, which live in
      subtropical south-central Florida, did not exhibit changes in day-to-day mass
      fluctuation relative to weather or climate variables or calendar date. Day-to-day
      mass fluctuations influenced mass fluctuation between the following third and
      fourth days. These changes were usually compensatory, indicating that jays are
      able to regulate their body mass on a short-term basis, despite strong
      differences in their roles in reproduction. During reproduction, jays have a
      relatively predictable and abundant food supply, thus the appropriate strategy
      may be to maintain a stable body mass that balances some energy reserves against
      maintaining a low body mass for efficient flight, as required during
      reproduction.

PMID- 30225179
TI  - Molecular typing and profiling of topoisomerase mutations causing resistance to
      ciprofloxacin and levofloxacin in Elizabethkingia species.
AB  - Objectives: Several Elizabethkingia species often exhibit extensive antibiotic
      resistance, causing infections associated with severe morbidity and high
      mortality rates worldwide. In this study, we determined fluoroquinolone
      susceptibility profiles of clinical Elizabethkingia spp. isolates and
      investigated the resistance mechanisms. Methods: In 2017-2018, 131
      Elizabethkingia spp. isolates were recovered from specimens collected at tertiary
      care centers in northern Taiwan. Initial species identification using the Vitek
      MS system and subsequent verification by 16S rRNA sequencing confirmed the
      presence of Elizabethkingia anophelis (n = 111), E. miricola (n = 11), and E.
      meningoseptica (n = 9). Fluoroquinolone susceptibility was determined using the
      microbroth dilution method, and fluoroquinolone resistance genes were analyzed by
      sequencing. Results: Among Elizabethkingia spp. isolates, 91% and 77% were
      resistant to ciprofloxacin and levofloxacin, respectively. The most prevalent
      alterations were two single mutations in GyrA, Ser83Ile, and Ser83Arg, detected
      in 76% of the isolates exhibiting fluoroquinolone MIC between 8 and 128 MUg/ml.
      Another GyrA single mutation, Asp87Asn, was identified in two quinolone-resistant
      E. miricola strains. None of the isolates had alterations in GyrB, ParC, or ParE.
      We developed a high-resolution melting assay for rapid identification of the
      prevalent gyrA gene mutations. The genetic relationship between the isolates was
      evaluated by random amplified polymorphic DNA PCR that yielded diverse
      pulsotypes, indicating the absence of any temporal or spatial overlap among the
      patients during hospitalization. Conclusion: Our analysis of fluoroquinolone
      resistant Elizabethkingia spp. isolates provides information for further research
      on the variations of the resistance mechanism and potential clinical guidance for
      infection management.

PMID- 30225180
TI  - Maxent estimation of aquatic Escherichia coli stream impairment.
AB  - Background: The leading cause of surface water impairment in United States'
      rivers and streams is pathogen contamination. Although use of fecal indicators
      has reduced human health risk, current approaches to identify and reduce exposure
      can be improved. One important knowledge gap within exposure assessment is
      characterization of complex fate and transport processes of fecal pollution.
      Novel modeling processes can inform watershed decision-making to improve exposure
      assessment. Methods: We used the ecological model, Maxent, and the fecal
      indicator bacterium Escherichia coli to identify environmental factors associated
      with surface water impairment. Samples were collected August, November, February,
      and May for 8 years on Sinking Creek in Northeast Tennessee and analyzed for 10
      water quality parameters and E. coli concentrations. Univariate and multivariate
      models estimated probability of impairment given the water quality parameters.
      Model performance was assessed using area under the receiving operating
      characteristic (AUC) and prediction accuracy, defined as the model's ability to
      predict both true positives (impairment) and true negatives (compliance).
      Univariate models generated action values, or environmental thresholds, to
      indicate potential E. coli impairment based on a single parameter. Multivariate
      models predicted probability of impairment given a suite of environmental
      variables, and jack-knife sensitivity analysis removed unresponsive variables to
      elicit a set of the most responsive parameters. Results: Water temperature
      univariate models performed best as indicated by AUC, but alkalinity models were
      the most accurate at correctly classifying impairment. Sensitivity analysis
      revealed that models were most sensitive to removal of specific conductance.
      Other sensitive variables included water temperature, dissolved oxygen,
      discharge, and NO3. The removal of dissolved oxygen improved model performance
      based on testing AUC, justifying development of two optimized multivariate
      models; a 5-variable model including all sensitive parameters, and a 4-variable
      model that excluded dissolved oxygen. Discussion: Results suggest that E. coli
      impairment in Sinking Creek is influenced by seasonality and agricultural run
      off, stressing the need for multi-month sampling along a stream continuum.
      Although discharge was not predictive of E. coli impairment alone, its
      interactive effect stresses the importance of both flow dependent and independent
      processes associated with E. coli impairment. This research also highlights the
      interactions between nutrient and fecal pollution, a key consideration for
      watersheds with multiple synergistic impairments. Although one indicator cannot
      mimic theplethora of existing pathogens in water, incorporating modeling can fine
      tune an indicator's utility, providing information concerning fate, transport,
      and source of fecal pollution while prioritizing resources and increasing
      confidence in decision making.

PMID- 30225182
TI  - Atypical Intraepidermal Melanocytic Proliferation Masked by a Tattoo:
      Implications for Tattoo Artists and Public Health Campaigns.
AB  - Tattoos have become increasingly popular worldwide. While tattoos carry a minimal
      risk of complications, previous reports have located malignant melanoma hidden
      within tattoos. We present a case of an atypical intraepidermal melanocytic
      proliferation masked by a large tattoo in a 39-year-old Caucasian male. Tattooed
      skin can be difficult to examine, particularly when the tattoos are dark,
      pigmented, and extensive. We demonstrate that a careful examination of tattooed
      skin leads to the early detection of atypical melanocytic proliferations. We
      present an extensive review of literature related to the relationship between
      tattoos and skin cancer, as well as public health recommendations for tattoo
      artists and individuals seeking to obtain tattoos. We urge a vigilant examination
      of tattooed skin and encourage collaboration between dermatologists and tattoo
      artists in promoting the detection of suspicious lesions prior and following
      tattooing.

PMID- 30225181
TI  - Distraction of cyclists: how does it influence their risky behaviors and traffic
      crashes?
AB  - Background: Undisputedly, traffic crashes constitute a public health concern
      whose impact and importance have been increasing during the past few decades.
      Specifically, road safety data have systematically shown how cyclists are highly
      vulnerable to suffering traffic crashes and severe injuries derived from them.
      Furthermore, although the empirical evidence is still very limited in this
      regard, in addition to other human factors involved in cycling crashes,
      distractions while cycling appear to be a major contributor to the road risk of
      cyclists. Objectives: The main objectives of this study were, first, to explore
      the prevalence and trends of cycling distractions within an international sample
      of bike users, and second, to determine the influence of such distractions on
      road crashes suffered by cyclists, simultaneously considering the explanatory
      role of risky behaviors (errors and traffic violations) as potentially mediating
      variables between cycling distractions and traffic crashes. Methods: For this
      cross-sectional study, we analyzed the data obtained from 1,064 cyclists-61.2%
      male and 38.8% female-from 20 different countries, who answered an on-line
      questionnaire on cycling-related features, habits, behaviors and accidents.
      Results: The prevalence of different cycling distractions oscillated between
      34.7% and 83.6%. The most common distractions were those related to the behavior
      of other users, physical elements of the road, weather conditions and phone
      calls. Age trends and differences were also found, thus establishing a positive
      association between age and distractibility during cycling. Furthermore, the
      effect of distractions on traffic crashes of cyclists was significant when tested
      together with age, risk perception and risky behaviors on the road. Conclusion:
      The results of this study support the hypotheses that distractions have a major
      prevalence among bike users, and that they play a significant role in the
      prediction of the traffic crash rates of cyclists, through the mediation of risky
      behaviors.

PMID- 30225183
TI  - A Case Report in Hemorrhagic Stroke: A Complex Disease Process and Requirement
      for a Multimodal Treatment Approach.
AB  - Intracerebral hemorrhage (ICH) with or without intraventricular hemorrhage (IVH)
      is a highly morbid disease process due to the mass effect and secondary injury
      that occurs upon the surrounding brain. Historically, surgical evacuation has
      failed to demonstrate improved outcomes in comparison to standard medical therapy
      likely due to the significant brain trauma when accessing the clot. Recent
      minimally invasive techniques have proposed a way to improve outcomes by reducing
      this injury. We report here a 62-year-old male with ICH and IVH with acute
      neurological deterioration due to hydrocephalus was found to have no improvement
      following external ventricular drainage. A repeat non-contrasted computed
      tomography (CT) head was obtained which demonstrated the worsening mass effect
      from peri-hematoma edema. Surgical intervention was employed that uses a variety
      of techniques (endoscopic and exoscopic visualization, stereotactic trans-sulcal
      approach and side cutting aspiration, and intraventricular thrombolytic therapy)
      to reduce cerebral trauma while effectively removing both ICH and IVH. The
      surgical intervention reduces the mass effect and associated secondary injury,
      lessens the likelihood of shunt placement and length of stay, and improves long
      term morbidity. We conclude that the effectiveness of surgical management of ICH
      could potentially be improved by employing a multifaceted approach to address the
      different characteristics of the hemorrhagic stroke.

PMID- 30225184
TI  - Traumatic Stress Epigenetics.
AB  - Purpose of Review: Traumatic stress has profound impacts on many domains of life,
      yet the mechanisms that confer risk for or resilience to the development of
      traumatic stress-related psychopathologies are still very much under
      investigation. The current review highlights recent developments in the field of
      traumatic stress epigenetics in humans. Recent Findings: Recent results reveal
      traumatic stress-related epigenetic dysregulation in neural, endocrine, and
      immune system genes and associated networks. Emerging work combining imaging with
      epigenetic measures holds promise for addressing the correspondence between
      peripheral and central effects of traumatic stress. A growing literature is also
      documenting the transgenerational effects of prenatal stress exposures in humans.
      Summary: Moving forward, increasing focus on epigenetic marks of traumatic stress
      in CNS tissue will create a clearer picture of the relevance of peripheral
      measures; PTSD brain banks will help in this regard. Similarly, leveraging
      multigenerational birth cohort data will do much to clarify the extent of
      transgenerational epigenetic effects of traumatic stress. Greater efforts should
      be made towards developing prospective studies with longitudinal design.

PMID- 30225185
TI  - DNA Repair Gene XRCC1 and XPD Polymorphisms and Gastric Cancer Risk: A Case
      Control Study Outcome from Kashmir, India.
AB  - Coding polymorphisms in several DNA repair genes have been reported to affect the
      DNA repair capacity and are associated with genetic susceptibility to many human
      cancers, including gastric cancer. An understanding of these DNA repair gene
      polymorphisms might assess not only the risk of humans exposed to environmental
      carcinogens but also their responses to different therapeutical approaches, which
      target the DNA repair pathway. In the present study, polymorphic variants of two
      DNA repair genes, XRCC1 Arg399Gln and XPD Lys751Gln, were chosen to be studied in
      association with gastric cancer susceptibility in the Kashmiri population. A
      total of 180 confirmed cases of gastric cancer (GC) and 200 hospital-based
      controls from Government Shri Maharaja Hari Singh Hospital, Srinagar, were
      included in the study. The genotyping for XRCC1 and XPD genes was carried out by
      polymerase chain reaction-restriction fragment length polymorphism. We found that
      tobacco smoking is strongly associated with GC risk (OR = 25.65; 95% CI: 5.49
      119.7). However, we did not find any association of polymorphism of XRCC1
      Arg399Gln (OR = 1.56; 95% CI: 0.32-7.82) and XPD Lys751Gln (OR = 0.46; CI: 0.10
      2.19) with GC risk in the study population. The combination of genotypes and
      gender stratification of XRCC1 and XPD genotypic frequency did not change the
      results. Consumption of large volumes of salt tea was also not associated with
      gastric cancer risk. Polymorphic variants of XRCC1 Arg399Gln and XPD Lys751Gln
      are not associated with the risk of gastric cancer in the Kashmiri population.
      However, replicative studies with larger sample size are needed to substantiate
      the findings.

PMID- 30225186
TI  - Post-traumatic fatal disseminated Apophysomyces elegans infection.
AB  - Mucorales infections typically occur in immunocompromised hosts. We describe a
      case of disseminated post-traumatic Apophysomyces elegans in an immunocompetent
      patient status-post soil inoculation. Fungi introduced at a deep arm laceration
      leads to neurovascular invasion and dissemination prior to amputation and
      systemic treatment. We specify strict post-traumatic wound surveillance protocol
      and roles of novel tissue tests to improve time to diagnosis and prognosis of
      frequently fatal post-traumatic Mucorales infections.

PMID- 30225187
TI  - MCM3 and Ki67 proliferation markers in odontogenic cysts and ameloblastoma.
AB  - Background: MCM3 is a marker of proliferation that has been used as a diagnostic
      or prognostic marker in many pathologic lesions. Purpose: The purpose of this
      study is to investigate the proliferative activity of dentigerous cysts,
      odontogenic keratocyst and ameloblastoma using minichromosome maintenance 3
      (MCM3) and compare it with Ki-67 proliferation marker. Methods: In this cross
      sectional study, 40 cases including 11 cases of dentigerous cyst, 14 odontogenic
      keratocyst, and 15 ameloblastoma were included. Immunohistochemical expression of
      MCM3 and Ki-67 were investigated and compared statistically using ANOVA, Chi
      square, Tukey and Spearman's correlation tests. Results: All subjects were
      positive for Ki-67 and MCM3. There was a significant difference in MCM3 and Ki-67
      expression among all groups. Compared to Ki-67, MCM3 exhibited a higher level of
      expression. Ameloblastoma and odontogenic keratocyst revealed higher expression
      rate of both markers in comparison to dentigerous cysts. Conclusion: The results
      showed MCM3 and Ki67 expression in the most common odontogenic cysts and tumors,
      especially more aggressive lesions. MCM3 might have a role in pathogenesis of
      these lesions and could be a reliable marker for assessing proliferation
      activity.

PMID- 30225188
TI  - Spontaneous mediastinitis with multiple esophageal abscess in the esophagus.
AB  - Acute mediastinitis (AM) is a rare and deadly disease without appropriate
      treatment. It is usually due to invasive medical procedures, being uncommon the
      spontaneous onset. We report a case of 49-year-old patient whose starting
      symptoms were dyspnea and oppressive epigastric pain.

PMID- 30225189
TI  - Recurrent alveolar hemorrhage: How do you treat that which you cannot see?
AB  - Diffuse alveolar hemorrhage (DAH) is a rare and life-threatening event which is
      characterized by bleeding into the alveolar spaces of the lung. Etiology of DAH
      can be broadly divided into immune and non-immune mediated disease. In the
      absence of infection or malignancy, an immunological workup is required to find
      the cause of alveolar bleed. Rarely, there is a failure to establish a definitive
      etiology in patients with DAH. In those scenarios, patients who do not respond to
      steroids, plasmapheresis should be considered as a rescue treatment to prevent
      catastrophic outcomes. Herein, we present a unique case of a 48-year-old male
      admitted with DAH of unknown etiology completely recovered after empirical
      plasmapheresis.

PMID- 30225190
TI  - Metastatic pulmonary melanoma complicated with erythroderma and recurrent sepsis.
AB  - Erythroderma is occasionally associated with lung cancer. Here we report a 69
      year-old male who has history of melanoma from 8 years ago presented with
      erythroderma associated with skin, soft tissue and pulmonary infection. CT chest
      showed a single enlarging right upper lobe lung nodule. Biopsy showed evidence of
      adenocarcinoma, and eventually proven to be metastatic melanoma. The patient
      improved after antibiotics and antifungal treatment. To our knowledge, this is
      the first case of melanoma metastasis presented as erythroderma as paraneoplastic
      syndrome.

PMID- 30225191
TI  - Extracellular matrix fistula plug for repair of bronchopleural fistula.
AB  - Introduction: Bronchopleural fistula (BPF) is a feared complication of pulmonary
      resection. Fistula plugs (FP) have been described as an adequate treatment in
      anorectal disease. We describe our early experience placing an FP in the
      treatment of BPF. Materials and methods: We retrospectively reviewed 5 patients
      for whom a FP was placed for BPF at our institution. Demographic data, initial
      perioperative information, method and technique of FP placement, and success is
      reported. Results: Five patients (4 male, 1 female) with a median age of 63 years
      (range, 57-76 years) underwent 6 FP placements for BPF. Two patients were post
      pneumonectomy and 3 patients post-lobectomy. The median time to presentation
      following surgery was 118 days (range 22-218). Upon bronchoscopic or operative re
      evaluation, 3 patients had successful cessation of their air leak at 0, 1 and 4
      days. Two of three patients subsequently underwent a thoracic muscle flap
      placement to augment healing. One patient had a persistent air leak despite 2
      separate FP placements. The air leak stopped with endobronchial valves (EBV)
      which were deployed proximal to the FP, 9 days after placement of the FP. Another
      patient had a successful muscle flap placed 80 days after FP placement. There
      were no complications associated with the FP. Three of five patients were deemed
      successfully treated with FP placement alone. Conclusion: In patients with a
      postoperative BPF and pleural window, placement of a FP had a modest success rate
      and can be considered as a treatment modality option for BPF.

PMID- 30225192
TI  - Renal infiltration presenting as acute kidney injury in Hodgkin lymphoma - A case
      report and review of the literature.
AB  - Renal involvement in Hodgkin lymphoma (HL) is rare, although extralymphatic
      disease is usually found. Acute kidney injury is a recognized presentation of non
      Hodgkin lymphoma, with bilateral kidney involvement, promptly requiring specific
      treatment. Regarding to HL, this manifestation is extremely rare and lacks
      pathologic description and management experiences. Herein, we describe a case of
      HL with atypical presentation as well as its management, current evaluation by
      PET-scan and histologic findings. This case report highlights clinical
      presentation and a successful experience on managing these cases. Moreover, it is
      important to drive biologic insights for understanding of kidney infiltration
      mechanism in HL.

PMID- 30225193
TI  - An unexpected diversity of trypanosomatids in fecal samples of great apes.
AB  - Charismatic great apes have been used widely and effectively as flagship species
      in conservation campaigns for decades. These iconic representatives of their
      ecosystems could also play a role as reservoirs of several zoonotic diseases.
      Recently it was demonstrated that African great apes can host Leishmania
      parasites (Kinetoplastea: Trypanosomatidae). Given that this finding raised a
      strong negative reaction from leishmania experts and the subsequent discussion
      did not lead to a clear resolution, we decided to analyze wild gorilla (Gorilla
      gorilla gorilla) and chimpanzee (Pan troglodytes troglodytes) fecal samples
      collected from the same area in Cameroon as in the original study. Fecal samples,
      used to circumvent the difficulties and ethics involved in obtaining blood
      samples from endangered wild apes, were screened by three different PCR assays
      for detection of Leishmania DNA. We did not detect any leishmania parasites in
      analyzed feces; however, sequencing of SSU rRNA revealed an unexpected diversity
      of free-living bodonids (Kinetoplastea: Bodonidae) and parasitic trypanosomatids
      (Kinetoplastea: Trypanosomatidae) other than Leishmania. A single detected
      Phytomonas species, found in chimpanzee feces, most likely originated from animal
      plant food. On the other hand, the presence of four free-living bodonid species
      and four parasitic insect monoxenous trypanosomatid, including two possible new
      species of the genus Herpetomonas, could be explained as ex post contamination of
      feces either from the environment or from flies (Diptera: Brachycera).

PMID- 30225195
TI  - Whole exome sequencing may be insufficient to cover the causality spectrum of
      rhabdomyolysis.

PMID- 30225194
TI  - Simultaneous ultra-high frequency photoacoustic microscopy and photoacoustic
      radiometry of zebrafish larvae in vivo.
AB  - With their optically transparent appearance, zebrafish larvae are readily imaged
      with optical-resolution photoacoustic (PA) microscopy (OR-PAM). Previous OR-PAM
      studies have mapped endogenous chromophores (e.g. melanin and hemoglobin) within
      larvae; however, anatomical features cannot be imaged with OR-PAM alone due to
      insufficient optical absorption. We have previously reported on the photoacoustic
      radiometry (PAR) technique, which can be used simultaneously with OR-PAM to
      generate images dependent upon the optical attenuation properties of a sample.
      Here we demonstrate application of the duplex PAR/PA technique for label-free
      imaging of the anatomy and vasculature of zebrafish larvae in vivo at 200 and 400
      MHz ultrasound detection frequencies. We then use the technique to assess the
      effects of anti-angiogenic drugs on the development of the larval vasculature.
      Our results demonstrate the effectiveness of simultaneous PAR/PA for acquiring
      anatomical images of optically transparent samples in vivo, and its potential
      applications in assessing drug efficacy and embryonic development.

PMID- 30225196
TI  - Coenzyme Q10 deficiency due to a COQ4 gene defect causes childhood-onset
      spinocerebellar ataxia and stroke-like episodes.

PMID- 30225198
TI  - Elevated CPK levels after hydrazine inhalation exposure in an F16 aircraft
      technician.
AB  - Hydrazine is a hazardous material that is commonly used in the pharmaceutical
      industry, as well as in rocket and jet fuels, including the emergency power unit
      of F-16 model jets. We present four ground crew technicians who were exposed to
      hydrazine for less than one minute, due to a voltage fall in an F-16 jet.
      Physical examinations were normal and none of the technicians were symptomatic
      for toxicity. One of the technicians had abnormal blood chemistry levels for
      liver and muscle enzymes: serum glutamic-oxaloacetic transaminase(SGOT)-321U/L,
      serum glutamate-pyruvate transaminase (SGPT)-123U/L, and creatine phosphokinase
      (CPK) 3300U/L. The CPK level peaked during hospitalization to 20960U/L at 36 h
      after the exposure, and subsequently declined. Upon release from the hospital, 48
      h after the exposure, the CPK level -was 9429U/L. In repeated tests one week and
      one year after exposure, liver function and CPK levels were normal. We conclude
      that evaluation of blood tests is important, in addition to a physical
      examination, in asymptomatic persons following exposure to even short term highly
      elevated levels of hydrazine.

PMID- 30225197
TI  - The therapeutics effects and toxic risk of Heracleum persicum Desf. extract on
      streptozotocin-induced diabetic rats.
AB  - There is an increasing interest against to fight of diabetes by using
      hypoglycemic plants in the world. The public thinks that Heracleum persicum (HP)
      has antidiabetic effect local consumer in Turkey. As far as our literature
      survey, no studies have been reported so far on antidiabetic effects and toxic
      risk potential of the HP lyophilized extract supplementation used in this study.
      The aim of this study, for the first time, was to investigate the therapeutic
      effects of diabetic complications, antioxidant properties and toxic risk
      potential of HP against experimentaly streptozotocin (STZ) induced diabetes in
      rats, which were evaluated by measuring the level of serum biomarker releated
      diabetes complications changes such glucose, insulin, c-peptide, lipid profile
      (LP), hepatic and renal damage biomarkers (HRDB), glucosylated hemoglobin
      (HbA1c), antioxidant defense system constituents (ADSCs), malondialdehyde (MDA)
      content measured in erythrocyte, brain, kidney and liver tissues, and alpha
      glucosidase activitiy of small intestine. The plant aqueous extract was allowed
      to freeze-dried under a vacuum at -54  degrees C to obtain a fine lyophilized
      extract. The study was performed on STZ-induced diabetic rats (45 mg/kg, body
      weight (bw), intraperitonally) designed as normal control (NC), diabetic control
      (DC), diabetes + acarbose (DAC) (20 mg/kg, bw), diabetes + HP (100 mg/kg, bw)
      (DH1), diabetes + HP (200 mg/kg, bw) (DH2) and diabetes + HP (400 mg/kg, bw)
      (DH3)] groups. The experimental process lasted 21 days. According to results; the
      levels of blood glucose (BG), glucosylated hemoglobin (HbA1c) and malondialdehyde
      (MDA) of DC group increased significantly (p<0.05) compared to NC group, whereas
      these parameters of the groups treated with oral administrations of HP plant
      lyophilized extract were observed significant (p<0.05) declines compared to DC.
      The biochemical analyses showed a considerable decrease in insulin and c-peptide
      levels and the fluctuated ADSCs in the DC group as compared to control group,
      whereas the extract supplementations diet restored the diabetic complications
      parameters towards to the NC. On the other hands, liver damage serum enzymes as
      serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels
      were incressed significantly (p<0.05) in the plant extract supplementations
      groups as compared to NC and DC groups. It was concluded that while the extracts
      of HP have had therapeutic effects on some complications caused by diabetes, but
      might be caused hepatocyte damage changes as the transport functions and membrane
      permeability of these cells, thus causing enzymes to leak.

PMID- 30225199
TI  - Pregnancy in a woman with recurrent immunoglobulin a nephropathy: A case report.
AB  - Immunoglobulin A nephropathy (IgAN) is the most common form of primary
      glomerulonephritis and is increasingly encountered in pregnancy. The obstetric
      and renal outcomes of pregnancy are controversial, however. Women with IgAN are
      at higher risk of hypertension, preeclampsia and foetal loss; the prognosis is
      worse for those who have advanced chronic kidney disease and proteinuria. Here we
      report the case of a 32-year-old nulliparous woman with chronic hypertension who
      conceived during an active phase of her IgAN, which had been diagnosed 8 years
      earlier. Antihypertensive therapies and a low-protein diet were key to her
      reaching 34 weeks' gestation with acceptable kidney function. Rupture of
      membranes occurred at 34 weeks 3 days' gestation and a healthy boy was delivered
      the next day. This report aims to provide clinicians with useful information for
      the management of patients with IgAN during pregnancy.

PMID- 30225200
TI  - Delayed systemic allergic dermatitis following Essure insert: A case report.
AB  - Hypersensitivity reaction to the nickel component of the Essure contraceptive
      micro-insert (Essure) is extremely rare. We present a case of a 41-year-old woman
      who reported a delayed systemic allergic reaction to the Essure. This is the
      fourth such case to be reported in the literature. Four years after Essure
      insertion, the patient developed systemic contact dermatitis secondary to the
      nickel component. The Essure was suspected as the cause after a positive allergy
      patch test result for nickel. An initial laparoscopic bilateral salpingectomy did
      not improve her symptoms (likely due to retained microfilament), but a subsequent
      hysterectomy resulted in complete resolution of symptoms. Nickel allergy is a
      rare but serious complication of the Essure and practitioners should be cognisant
      of its role in hypersensitivity reactions.

PMID- 30225201
TI  - Hydrosalpinx with acute abdominal pain during the third trimester of pregnancy: A
      case report.
AB  - Background: Acute abdomen in pregnancy is a unique clinical challenge. We report
      a rare case of hydrosalpinx presenting as acute abdomen in the third trimester of
      pregnancy in the absence of infection and hormonal treatment. Case: A 38-year-old
      Caucasian woman (gravida 4, para 3), at an estimated 29 weeks of a spontaneous
      singleton pregnancy, presented to the emergency department with severe abdominal
      pain in the right lower quadrant, which had been present for three days. Magnetic
      resonance imaging (MRI) demonstrated a right-sided hydrosalpinx. It was
      successfully treated with conservative treatment and the patient delivered
      vaginally at term without complication. Conclusion: Hydrosalpinx should be
      considered as one of the differential diagnoses for acute abdomen during
      pregnancy. A multidisciplinary approach is recommended, with a careful work-up,
      due to the risks to both fetus and mother.

PMID- 30225202
TI  - Ovarian necrosis due to S. pyogenes septic thrombophlebitis: A case report.
AB  - The incidence of systemic infection attributed to group A streptococci (GAS) is
      increasing, mainly in postpartum women. Such infections require multidisciplinary
      management and prompt treatment, but an atypical presentation can delay
      diagnosis. We report the case of a 24-year-old woman admitted to the emergency
      department for evaluation. She had acute abdominal pain and fever 18 h after
      insertion of a levonorgestrel intrauterine device (IUD). She had a normal vaginal
      delivery 45 days earlier, and no other significant medical background. In a few
      hours the symptoms worsened, with rapid progression towards multiorgan failure.
      Differential diagnoses of late ovarian thrombophlebitis and ovarian torsion were
      considered. Laparoscopic surgery revealed the absence of ovarian torsion. The
      microbiologic culture of the IUD showed colonization by GAS. The sudden onset of
      shock-like symptoms in a postpartum woman with rapid progression towards
      multiorgan failure should prompt consideration of a diagnosis of GAS infection,
      so that appropriate treatment can be initiated to avoid the possible fatal
      consequences of this aggressive infection.

PMID- 30225204
TI  - Aberration correction for low voltage optimized transmission electron microscopy.
AB  - Further development of low voltage electron microscopy leads to an aberration
      correction of the device in order to improve its spatial resolution. The
      integration of a corrector to a desktop transmission electron microscope with
      exclusively low-voltage design seems to be a challenging task. The benefits and
      potential of the Rose hexapole corrector implemented to such a system are
      critically considered in this paper. The feasibility of miniaturized corrector
      suitable for desktop LVEM is especially discussed, including the aspect of
      corrector contribution to chromatic aberration that appears to be crucial.
      Optimal corrector parameters and resolution limits of such a system are proposed.
      *Improved spatial resolution*Spherical aberration correction*Permanent magnet
      transfer lenses.

PMID- 30225205
TI  - Performance evaluation of friction stir welding using machine learning
      approaches.
AB  - The aim of the present study is to evaluate the potential of sophisticated
      machine learning methodologies, i.e. Gaussian process (GPR) regression, support
      vector machining (SVM), and multi-linear regression (MLR) for ultimate tensile
      strength (UTS) of friction stir welded joint. Three regression models are
      developed on the above methodologies. These models are projected to study the
      incongruity between the experimental and predicted outcomes and preferred the
      preeminent model according to their evaluation parameter performances. Out of 25
      readings, 19 readings are selected for training models whereas remaining is used
      for testing models. Input process parameters consist of rotational speed (rpm),
      and feed rate (mm/min) whereas UTS is considered as output. Two kernel functions
      i.e. Pearson VII (PUK) and radial based kernel function (RBF) are used with both
      GPR and SVM regression. It is concluded that the GPR approach works better than
      SVM and MLR techniques. Therefore, GPR approach is used successfully for
      predicting the UTS of FS welded joint.

PMID- 30225203
TI  - Efficient enrichment cloning of TAL effector genes from Xanthomonas.
AB  - Many plant-pathogenic xanthomonads use a type III secretion system to translocate
      Transcription Activator-Like (TAL) effectors into eukaryotic host cells where
      they act as transcription factors. Target genes are induced upon binding of a TAL
      effector to double-stranded DNA in a sequence-specific manner. DNA binding is
      governed by a highly repetitive protein domain, which consists of an array of
      nearly identical repeats of ca. 102 base pairs. Many species and pathovars of
      Xanthomonas, including pathogens of rice, cereals, cassava, citrus and cotton,
      encode multiple TAL effectors in their genomes. Some of the TAL effectors have
      been shown to act as key pathogenicity factors, which induce the expression of
      susceptibility genes to the benefit of the pathogen. However, due to the
      repetitive character and the presence of multiple gene copies, high-throughput
      cloning of TAL effector genes remains a challenge. In order to isolate complete
      TAL effector gene repertoires, we developed an enrichment cloning strategy based
      on *genome-informed in silico optimization of restriction digestions,*selective
      restriction digestion of genomic DNA, and*size fractionation of DNA fragments.
      Our rapid, cheap and powerful method allows efficient cloning of TAL effector
      genes from xanthomonads, as demonstrated for two rice-pathogenic strains of
      Xanthomonas oryzae from Africa.

PMID- 30225206
TI  - Adapting open-source drone autopilots for real-time iceberg observations.
AB  - Drone autopilots are naturally suited for real-time iceberg tracking as they
      measure position and orientation (pitch, roll, and heading) and they transmit
      these data to a ground station. We powered an ArduPilot Mega (APM) 2.6 with a 5V
      11 Ah lithium ion battery (a smartphone power bank), placed the APM and battery
      in a waterproof sportsman's box, and tossed the box and its contents by hand onto
      an 80 m-long iceberg from an 8 m boat. The data stream could be viewed on a
      laptop, which greatly enhanced safety while collecting
      conductivity/temperature/depth (CTD) profiles from the small boat in the
      iceberg's vicinity. The 10 s position data allowed us to compute the distance of
      each CTD profile to the iceberg, which is necessary to determine if a given CTD
      profile was collected within the iceberg's meltwater plume. The APM position data
      greatly reduced position uncertainty when compared to 5 min position data
      obtained from a Spot Trace unit. The APM functioned for over 10 h without
      depleting the battery. We describe the specific hardware used and the software
      settings necessary to use the APM as a real-time iceberg tracker. Furthermore,
      the methods described here apply to all Ardupilot-compatible autopilots. Given
      the low cost ($90) and ease of use, drone autopilots like the APM should be
      included as another tool for studying iceberg motion and for enhancing safety of
      marine operations. *Commercial off-the-shelf iceberg trackers are typically
      configured to record positions over relatively long intervals (months to years)
      and are not well-suited for short-term (hours to few days), high-frequency
      monitoring*Drone autopilots are cheap and provide high-frequency (>1 Hz) and real
      time information about iceberg drift and orientation*Drone autopilots and ground
      control software can be easily adapted to studies of iceberg-ocean interactions
      and operational iceberg management.

PMID- 30225208
TI  - Preface: lung cancer in never smokers.

PMID- 30225207
TI  - Isolation by Miniaturized Culture Chip of an Antarctic bacterium Aequorivita sp.
      with antimicrobial and anthelmintic activity.
AB  - Microbes are prolific sources of bioactive molecules; however, the cultivability
      issue has severely hampered access to microbial diversity. Novel secondary
      metabolites from as-yet-unknown or atypical microorganisms from extreme
      environments have realistic potential to lead to new drugs with benefits for
      human health. Here, we used a novel approach that mimics the natural environment
      by using a Miniaturized Culture Chip allowing the isolation of several bacterial
      strains from Antarctic shallow water sediments under near natural conditions. A
      Gram-negative Antarctic bacterium belonging to the genus Aequorivita was
      subjected to further analyses. The Aequorivita sp. genome was sequenced and a
      bioinformatic approach was applied to identify biosynthetic gene clusters. The
      extract of the Aequorivita sp. showed antimicrobial and anthelmintic activity
      towards Multidrug resistant bacteria and the nematode Caenorhabditis elegans.
      This is the first multi-approach study exploring the genomics and
      biotechnological potential of the genus Aequorivita that is a promising candidate
      for pharmaceutical applications.

PMID- 30225209
TI  - A quantitative method for assessing smoke associated molecular damage in lung
      cancers.
AB  - Background: While tobacco exposure is the cause of the vast majority of lung
      cancers, an important percentage arise in lifetime never smokers. Documenting the
      precise extent of tobacco induced molecular changes may be of importance. Also,
      the contribution of environmental tobacco smoke (ETS) is difficult to assess.
      Methods: We developed and validated a quantitative method to assess the extent of
      tobacco related molecular damage by combing the most characteristic changes
      associated with tobacco smoke, the tumor mutation burden (TMB) and type of
      molecular changes present in lung cancers. Using maximum entropy (MaxEnt) as a
      classifier, we developed a F score. F score values >0 were considered to show
      evidence of tobacco related molecular damage, while values <=0 were considered to
      lack evidence of tobacco related molecular damage. Compared to the stated patient
      tobacco exposure histories, the F scores had sensitivity, specificity and
      accuracy values of 85-87%. Using this method, we analyzed public data sets of
      lung adenocarcinoma (LUAD), lung squamous cell (LUSC) and small cell lung cancer
      (SCLC). Results: Less than 10% of LUSCs and SCLCs had negative F scores, while
      27% to 35% of LUADs had positive scores. The F score showed a highly significant
      downward trend when LUADs were subdivided into the following categories: ever,
      reformed <=15 years, reformed >15 years and never smokers. Most of the examined
      bronchial carcinoids (a lung cancer type not associated with smoke exposure) had
      negative F scores. In addition, most LUADs with EGFR mutations had negative F
      scores, while almost all with KRAS mutations had positive scores. Conclusions: We
      have established and validated a quantitative assay that will be of use in
      assessing the presence and degree of smoke associated molecular damage in lung
      cancers arising in ever and never smokers.

PMID- 30225210
TI  - Lung cancer in never smokers-the East Asian experience.
AB  - Approximately one third of all lung cancer patients in East Asia are never
      smokers. Furthermore, the proportion of lung cancer in never smokers (LCINS) has
      been increasing over time. Never-smokers are more often diagnosed with
      adenocarcinoma in East Asia, a subtype largely defined by oncogenic drivers. In
      this subgroup of patients, as high as 90% of patients have been found to harbor
      well-known oncogenic mutations and can be successfully managed with targeted
      therapies inhibiting specific oncogenic mutant kinases. EGFR tyrosine kinase
      inhibitor (EGFR-TKI) treatment has been the most important targeted therapy in
      lung adenocarcinoma from East Asian never-smokers as approximately 70% of these
      patients have the opportunity to receive EGFR-TKI treatment. Lung squamous cell
      carcinoma (SQCC) and small cell lung cancer (SCLC) are two common histologic
      types of smoking-related non-small cell lung cancer (NSCLC). The proportion of
      never-smokers with SQCC and SCLC in East Asian patients seems to be higher than
      that in Caucasian patients. Recent studies also suggest that lung SQCC and SCLC
      in never-smokers may be distinct subtypes. Therefore, better understanding of the
      biologic characteristics of these subtypes of patients may provide new insights
      for the treatment. In this review, we will provide an overview of East Asian
      experience in the treatment of advanced, never-smoking lung cancer, focusing on
      etiologic factors in the development of LCINS, targeted therapy for never-smokers
      with adenocarcinoma, distinct characteristics of never-smokers with lung SQCC and
      SCLC, and the role of immunotherapy in never-smokers with NSCLC.

PMID- 30225212
TI  - Ground-glass nodules of the lung in never-smokers and smokers: clinical and
      genetic insights.
AB  - Pulmonary ground-glass nodules (GGNs) are hazy radiological findings on computed
      tomography (CT). GGNs are detected more often in never-smokers. Retrospective and
      prospective studies have revealed that approximately 20% of pure GGNs and 40% of
      part-solid GGNs gradually grow or increase their solid components, whereas others
      remain stable for years. Most persistent or growing GGNs are lung adenocarcinomas
      or their preinvasive lesions. To distinguish GGNs with growth from those without
      growth, GGNs should be followed for at least 5 years. Lesion size and smoking
      history are predictors of GGN growth. Genetic analyses of resected GGNs have
      suggested that EGFR mutations are also predictors for growth but a subset of KRAS
      or BRAF-mutated GGNs may undergo spontaneous regression because the frequencies
      of KRAS or BRAF mutations decrease with the advance of pathological invasiveness.
      Although lobectomy is the standard surgical procedure for lung cancer, limited
      surgery such as wedge resection or segmentectomy for lung cancers <=2 cm with
      consolidation/tumor ratio <=0.25 can be a viable alternative based on the recent
      clinical trial. Further genetic analyses and clinical trials can contribute to
      elucidation of the biological aspects of preinvasive adenocarcinoma and the
      development of less invasive management strategies for patients with GGNs.

PMID- 30225211
TI  - Autochthonous murine models for the study of smoker and never-smoker associated
      lung cancers.
AB  - Lung cancer accounts for the greatest number of cancer deaths in the world.
      Tobacco smoke-associated cancers constitute the majority of lung cancer cases but
      never-smoker cancers comprise a significant and increasing fraction of cases.
      Recent genomic and transcriptomic sequencing efforts of lung cancers have
      revealed distinct sets of genetic aberrations of smoker and never-smoker lung
      cancers that implicate disparate biology and therapeutic strategies.
      Autochthonous mouse models have contributed greatly to our understanding of lung
      cancer biology and identified novel therapeutic targets and strategies in the era
      of targeted therapy. With the emergence of immuno-oncology, mouse models may
      continue to serve as valuable platforms for novel biological insights and
      therapeutic strategies. Here, we will review the variety of available
      autochthonous mouse models of lung cancer, their relation to human smoker and
      never-smoker lung cancers, and their application to immuno-oncology and immune
      checkpoint blockade that is revolutionizing lung cancer therapy.

PMID- 30225214
TI  - In vivo biodistribution of topical low molecular weight heparin-taurocholate in a
      neovascularized mouse cornea.
AB  - AIM: To investigate the ocular biodistribution and clearance of topically
      administered 7-taurocholic acid conjugated low-molecular weight heparin (LHT7) in
      a neovascularized mouse cornea using an in vivo optical imaging system. METHODS:
      A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal
      neovascularization (CoNV) was induced in the inferior cornea (IC) of each animal
      by penetrating the stroma with two interrupted sutures. The development of CoNV
      was verified after one week and the area of each neovascularized region was
      measured. A near-infrared fluorescent probe of 20 umol/L Cy5.5 labeled LHT7 (LHT7
      Cy5.5) in 0.02 mL solution was topically instilled onto the cornea in the
      experimental group (n=5). Free-Cy5.5 of 20 umol/L in 0.02 mL was instilled in the
      control group (n=5). In vivo optical images were obtained before instillation and
      5min, 2, 4, and 6h after instillation. The intensities were separately measured
      at the superior cornea (SC) and the IC. RESULTS: The mean CoNV areas were 1.97+/
      0.17 mm2 and 1.92+/-0.96 mm2 in the experimental and control groups, respectively
      (P=0.832). The SC remained normal in all 10 subject animals. The IC intensity of
      the LHT7-Cy5.5 was greater than the SC intensity at 5min (P=0.038), 2h (P=0.041),
      and 4h (P=0.041) after application. The IC intensity fell to less than half of
      its initial value (42.9%+/-8.6%) at 6h in the experimental group. In the control
      mice, here were no significant differences in the free-Cy5.5 intensity between
      the IC and SC. CONCLUSION: Topically administered LHT7 shows a high
      biodistribution in CoNV areas for 4h and should be reapplied accordingly to
      maintain its effects. In vivo optical imaging can be a useful tool for evaluating
      the ocular biodistribution of a drug in an animal model.

PMID- 30225213
TI  - Inherited lung cancer syndromes targeting never smokers.
AB  - Lung cancer is the leading cause of cancer death worldwide. Most of lung cancers
      develop sporadically and thus inherited lung cancers are rare. Several reports
      show that germline mutations in the kinase domain of epidermal growth factor
      receptor (EGFR) such as R776G, R776H, T790M, V843I and P848L, predispose to
      develop lung cancer. Most lung cancer cases with germline EGFR T790M mutations
      had secondary EGFR somatic mutations. Never smokers with germline EGFR T790M
      mutations develop lung cancer more frequently than ever smokers. In addition,
      germline EGFR T790M mutations favored female gender. Therefore, germline EGFR
      T790M mutations result in a unique inherited lung cancer syndrome targeting never
      smokers. The authors previously reported a Japanese familial lung cancer pedigree
      with germline mutations in the transmembrane domain of human epidermal growth
      factor receptor 2 (HER2). The female proband and her mother in this pedigree, who
      were light or never smokers, developed multiple lung adenocarcinomas, and had
      germline HER2 G660D mutations. They had no EGFR somatic mutations or other genes
      known to cause lung cancers. Although we know only one pedigree with germline
      HER2 mutations, these mutations may also cause inherited lung cancers targeting
      female never smokers. Based on our in vitro analyses, we administered HER2
      inhibitor afatinib to the proband and achieved partial response. These lung
      cancers arising from germline mutations of receptor tyrosine kinases such as EGFR
      and HER2 may have different features from those with sporadic mutations.

PMID- 30225215
TI  - Cell death and survival following manual and femtosecond laser-assisted
      capsulotomy in age-related cataract.
AB  - AIM: To study molecular and morphological changes in lens epithelial cells
      following femtosecond laser-assisted and manually performed continuous
      curvilinear capsulotomy (CCC) in order to get information about these methods
      regarding their potential role in the induction of development of secondary
      cataract. METHODS: Anterior lens capsules (ALC) were removed from 40 patients
      with age-related cataract by manual CCC and by femtosecond laser-assisted
      capsulotomy (FLAC). Samples removed by manual CCC were assorted in group 1, FLAC
      samples were classified in group 2. Morphology of lens epithelial cells was
      examined with light and electron microscopes. Following capsulotomy, expressions
      of p53, Bcl-2 and cyclin D1 genes were analyzed with reverse transcriptase
      polymerase chain reaction. Immunohistochemistry was used to detect the pro
      apoptotic p53 in the epithelial cells. RESULTS: Light and electron microscopic
      examination showed that ALC of group 1 contained more degenerating cells
      following manual CCC than after FLAC. The expression level of p53 was higher
      after manual than laser-assisted surgery. Immunocytochemistry indicated
      significantly higher number of cells containing p53 protein in the manual CCC
      group than following FLAC. Bcl-2 and cyclin D1 gene expression levels were
      slightly lower following manual CCC than after FLAC, but the difference was not
      significant. CONCLUSION: Manually removed ALC shows slightly, but not
      significantly larger damage due to the mechanical stretching and pulling of the
      capsule than those removed using FLAC.

PMID- 30225216
TI  - Effects of LY294002 on the function of retinal endothelial cell in vitro.
AB  - AIM: To study the effects of LY294002 [phosphatidylinositol 3-kinase (PI3K)
      inhibitor] on the function and mechanisms of retinal endothelial cells (RECs) in
      vitro. METHODS: RECs were randomly divided into control group and LY294002
      treatment group. RECs in the control group were placed the incubator for hypoxic
      exposure in vitro. RECs in the LY294002 treatment group were pretreated with
      LY294002 (40 umol/L) under hypoxic condition. The expression of matrix
      metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), and
      apoptosis and proliferation of RECs were evaluated with Western blot, real-time
      reverse transcription-polymerase chain reaction (RT-PCR), and flow cytometric
      analysis, correspondently. RESULTS: Compared with the control group, treating the
      RECs with LY294002 was able to remarkably inhibit cell proliferation rates
      (t1d=2.13, t2d=2.65, t3d=2.36, t4d=2.06, all P<0.05). Flow cytometric analysis
      indicated that a moderate increase in apoptosis in the LY294002 treatment group
      compared to the control group (t=2.51, P<0.05). The expression of MMP-2, MMP-9
      and VEGF were downregulated in the LY294002 treatment group by Western blot and
      real-time RT-PCR (all P<0.05). CONCLUSION: LY294002 regulates the function of
      RECs by reducing the expression of MMP-2, MMP-9, and VEGF in vitro. LY294002 may
      provide an effective method for preventing pathological angiogenesis.

PMID- 30225217
TI  - Influence of polymorphisms in VEGF, ACE, TNF and GST genes on the susceptibility
      to retinopathy of prematurity among Chinese infants.
AB  - AIM: To investigate common polymorphisms in VEGF, ACE, TNF and GST genes with
      retinopathy of prematurity (ROP) risk among Chinese infants. METHODS: Nine
      polymorphisms in the above genes were genotyped on 724 advanced cases of ROP and
      878 prematurely-born infants of low birth weight who were without any
      ophthalmologic disease. The frequencies of the polymorphisms were compared
      between cases and controls to identify the association present, if any. RESULTS:
      Of the nine polymorphisms, only two showed significant associations: ACE
      insertion deletion (ID) polymorphism (P=0.031) and TNF -308G/A polymorphism
      (P<0.001). The former was associated with a reduced ROP risk [ID genotype,
      adjusted OR (aOR): 0.603, 95%CI: 0.427-0.893, P=0.034; DD genotype, aOR: 0.468,
      95%CI: 0.229-0.626, P=0.002], while the latter showed an increased risk (GA
      genotype, aOR: 1.956, 95%CI: 1.396-2.465, P<0.001; AA genotype, aOR: 2.809,
      95%CI: 1.802-4.484, P<0.001). The association was also noted at the allele level
      (ACE D allele aOR: 0.698, 95%CI: 0.294-0.883, P<0.001; TNF -308A allele aOR:
      1.776, 95%CI: 1.446-2.561, P<0.001). CONCLUSION: The ACE ID polymorphism can
      protect against ROP development while the TNF -308G/A can increase the risk of
      the disease among Chinese infants.

PMID- 30225218
TI  - Frequency of IL-10-producing regulatory B cells associated with disease activity
      in thyroid-associated orbitopathy.
AB  - AIM: To investigate the association between IL-10-producing regulatory B (B10)
      cells and the clinical features of thyroid-associated orbitopathy (TAO). METHODS:
      A total of 30 patients with TAO were recruited at Zhongshan Ophthalmic Center
      from May 2015 to December 2015. Peripheral blood mononuclear cells (PBMCs) were
      separated from blood samples of 30 TAO patients and 16 healthy controls and
      stimulated with CD40 ligand and CpG for 48h. The frequency of IL-10+ B cells was
      examined by flow cytometry and the correlation between the frequency of IL-10+ B
      cells and clinical features of TAO was analyzed by SPSS. RESULTS: The frequency
      of IL-10+ B cells among CD19+ B cells in TAO patients was significantly lower
      than in healthy controls (TAO: 4.66%+/-1.88% vs healthy control: 6.82%+/-2.40%,
      P<0.01). The frequency of IL-10+ B cells showed a positive correlation with
      disease activity of TAO measured by Clinical Activity Score (CAS) (r=0.50,
      P<0.01), and became higher in TAO patients with family history of Graves' disease
      (GD) (P=0.04). CONCLUSION: The decrease of the frequency of IL-10+ B cells in TAO
      patients indicates the deficiency of B10 cells in TAO, and the positive
      association with disease activity suggests its important role in TAO inflammation
      regulation.

PMID- 30225219
TI  - Expression of multidrug-resistance associated proteins in human retinoblastoma
      treated by primary enucleation.
AB  - AIM: To reveal the expression of multidrug-resistance associated proteins:
      glutathione-S-transferase pi (GSTpi), P-glycoprotein (P-gp) and vault protein
      lung resistance protein (LRP) in retinoblastoma (RB) without any conservative
      treatment before primary enucleation and to correlate this expression with
      histopathological tumor features. METHODS: A total of 42 specimens of RB
      undergone primary enucleation were selected for the research. Sections from the
      formalin-fixed, paraffin-embedded specimens were stained with HE and
      immunohistochemistry to detect the expression of GSTpi, P-gp and LRP. RESULTS:
      GSTpi was expressed in 39/42 (92.86%) RBs and in 9/9 (100%) well-differentiated
      RBs. P-gp/GSTpi was found in 30 (71.42%) of 42 RBs. Totally 9 (21.43%) tumors
      were well differentiated and 33 (78.57%) were poorly differentiated. Totally 15
      (35.71%) eyes had optic nerve (ON) tumor invasion, 36 (85.71%) had choroidal
      tumor invasion, and 14 (33.33%) had simultaneous choroidal and ON invasion. There
      was no statistically significant relationship between P-gp, GSTpi, LRP positivity
      and the degree of ocular layer tumor invasion and ON tumor invasion (P>0.05).
      CONCLUSION: RB intrinsically expresses GSTpi, P-gp and LRP. GSTpi expression is
      positive in 100% well-differentiation ones, so in which way it is correlated with
      differentiation. But the other two proteins expressions are not related to tumor
      differentiation and to the degree of tumor invasion. GSTpi may be a new target of
      chemotherapy in RB.

PMID- 30225220
TI  - Pterygial body epithelium domination of pterygial proliferation with TCF4 as a
      potential key factor.
AB  - AIM: To characterize the proliferative capacity of pterygial epithelium in
      different regions (head, neck and body) of pterygium and explore the function of
      transcription factor 4 (TCF4) in pterygium proliferation. METHODS: Thirty
      pterygium tissues and 10 normal conjunctival tissues were obtained from Zhongshan
      Ophthalmic Center (ZOC) and Guangdong Eye Bank, respectively. Proliferative
      capacity of head, neck and body in pterygial epithelium was measured using clonal
      analysis, fold growth analysis and expression profile of proliferative markers
      revealed by immunofluorescent staining and real-time PCR. The expression of TCF4
      was highlighted by double immunofluorescent staining with other proliferation
      related markers such as proliferating cell nuclear antigen (PCNA) and ATP-binding
      cassette sub-family G member 2 (ABCG2). RESULTS: The proliferative potential of
      pterygial epithelium was higher than that of normal conjunctival epithelium. High
      expression levels of proliferative markers (P63alpha, PCNA and ABCG2) in
      pterygial body epithelium were observed in immunofluorescent staining and real
      time PCR (P<0.05). Also, epithelial cells isolated from pterygial body
      demonstrated higher proliferative capacity in clonal analysis and fold growth
      analysis, than those isolated from the head and neck regions. The TCF4 expression
      in pterygial epithelium was similar to other proliferative markers (P63alpha,
      PCNA and ABCG2), as higher in pterygial body than head and neck. Moreover, TCF4
      showed coexpression with other proliferation-related markers (PCNA and ABCG2) in
      the double immunofluorescent staining experiment. CONCLUSION: The proliferative
      capacity in pterygial body epithelium is prominent than the head and neck
      regions, and upregulated TCF4 may be associated with enhanced proliferation in
      the pterygium.

PMID- 30225221
TI  - Establishment of an acute extraocular muscle injury model in cats.
AB  - AIM: To describe an acute extraocular muscle injury model in cats. METHODS:
      Seventy-two cats were randomly divided into 6 groups (12 cats per group). Cats'
      left lateral recti were clamped using a surgical needle holder with a clamping
      strength of 2 (Groups A and D), 4 (Groups B and E) and 6 kg (Groups C and F). The
      right lateral recti were treated as controls. On the 4th and 7th days,
      hematoxylin eosin (HE) staining, immunohistochemical staining for proliferating
      cell nuclear antigen (PCNA), muscle force measurements and ocular alignment
      changes were performed to evaluate the extent of injuries. RESULTS: The
      morphological changes were graded as mild, moderate or severe by HE staining in
      all experiment groups. PCNA immunohistochemical staining indicated repairment of
      muscle fibers in the damaged area. On the 4th and 7th days after clamping, the
      injured lateral muscle exhibited an elevated threshold for electric stimulation.
      The muscle forces among groups 2, 4 and 6 kg injury at 4d (Groups A, B and C)
      were statistically significant (P<0.05), but no significant differences were
      noted among groups 2, 4 and 6 kg injury at 7d (Groups D, E and F) (P>0.05),
      respectively. In addition, medial deviation in ocular alignment was also present
      to various degrees in all groups. CONCLUSION: A cat model of acute extraocular
      muscle injury can be established by rectus clamping. Different clamping strengths
      can make different degrees of muscle injury. This model may help the future study
      in the acute extraocular muscle injury.

PMID- 30225222
TI  - Biomarker identification of thyroid associated ophthalmopathy using microarray
      data.
AB  - AIM: To uncover the underlying pathogenesis of thyroid associated ophthalmopathy
      (TAO) and explore potential biomarkers of this disease. METHODS: The expression
      profile GSE9340, which was downloaded from Gene Expression Omnibus database,
      included 18 specimens from 10 TAO patients and 8 hyperthyroidism patients without
      ophthalmopathy. The platform was HumanRef-8 v2 Expression BeadChip. Raw data were
      normalized using preprocess. Core package and the differentially expressed genes
      (DEGs) were identified based on t-test with limma package of R. Functional
      enrichment analyses were performed recruiting the DAVID tool. Based on STRING
      database, a protein-protein interaction (PPI) network was constructed, from which
      a module was extracted. The functional enrichment for genes in the module was
      performed by the BinGO plugin. RESULTS: In total, 861 DEGs (433 up-regulated and
      428 down-regulated) between TAO patients and hyperthyroidism patients without
      ophthalmopathy were identified. Crucial nodes in the PPI network included TPX2,
      CDCA5, PRC1, KIF23 and MKI67, which were also remarkable in the module and all
      enriched in cell cycle process. Additionally, MKI67 was highly correlated with
      TAO. Besides, the DEGs of GTF2F1, SMC3, USF1 and ZNF263 were predicted as
      transcription factors (TFs). CONCLUSION: Several crucial genes are identified
      such as TPX2, CDCA5, PRC1 and KIF23, which all might play significant roles in
      TAO via the regulation of cell cycle process. Regulatory relationships between
      TPX2 and CDCA5 as well as between PRC1 and KIF23 may exist. Additionally, MKI67
      may be a potent biomarker of TAO, and SMC3 and ZNF263 may exert their roles as
      TFs in TAO progression.

PMID- 30225223
TI  - The inflammation influence on corneal surface after frontalis suspension surgery.
AB  - AIM: To study the influence of frontalis muscle flap suspension on ocular surface
      by analyzing the clinical features and inflammatory cytokines. METHODS: A
      prospective, observational case series. Thirty-one eyes of 25 patients with
      severe congenital blepharoptosis who underwent frontalis muscle flap suspension
      surgery with at least 6mo of follow-up were included in the study. The main
      outcome measures were margin reflex distance 1 (MRD1), degree of lagophthalmos,
      ocular surface disease index (OSDI), fluorescein staining (Fl), tear break-up
      time (BUT), Schirmer I test, and inflammatory cytokine assay. RESULTS: The
      degrees of lagophthalmos significantly increased after surgery. The OSDI scores
      significantly increased 1wk postoperatively and then decreased 4wk after
      operation. The Fl scores reflected corneal epithelial defects in sixteen patients
      at early stage postoperatively. The BUT and Schirmer I test values remained
      stable and did not show change compared to those before surgery. The inflammatory
      cytokines in conjunctival epithelial cells (including IL-1beta, IL-6, IL-8, TNF
      alpha, and IL-17A) significantly increased 1wk after the surgery (P<0.001), then
      returned to the normal level at 24wk postoperatively. The levels of inflammatory
      cytokine IL-1beta, IL-6, IL-8, TNF-alpha, and IL-17A elevated significantly and
      were positively correlated with OSDI and Fl scores. CONCLUSION: Frontalis muscle
      flap suspension surgery results in lagophthalmos in early period of post
      operation and relieved after months. The elevation of inflammatory cytokines
      level may participate in the occurrence of corneal epithelial defects at the
      early postoperative stage.

PMID- 30225224
TI  - Lipid layer thickness and tear meniscus height measurements for the differential
      diagnosis of evaporative dry eye subtypes.
AB  - AIM: To explore a new diagnostic index for differentiating the evaporative dry
      eye (EDE) subtypes by analysis of their respective clinical characteristics.
      METHODS: A cross-sectional study of 139 patients (139 eyes) with EDE who were
      enrolled and classified as obstructive meibomian gland dysfunction (MGD) (n=81)
      and non-obstructive MGD (n=58) EDE. All patients completed a Standard Patient
      Evaluation of Eye Dryness (SPEED) questionnaire and were evaluated for average
      lipid layer thickness (LLT), tear meniscus height measurements (TMH), tear break
      up time (TBUT), ocular surface staining score, Schirmer I test (SIT), lid margin
      abnormalities, and meibomian gland function and morphology. RESULTS: Age, average
      LLT, TMH, scores of lid margin abnormalities, meibum quality, meibomian gland
      loss (MGL) (all P<=0.001), and TBUT (P=0.03) were all significantly different
      between obstructive MGD EDE patients and non-obstructive MGD EDE patients.
      Average LLT in obstructive MGD EDE was correlated with meibomian expressibility
      (r=-0.541, P<=0.001), lid margin abnormalities were marginally not significant
      (r=0.197, P=0.077), and TMH was correlated with MGL (total MGL: r=0.552,
      P<=0.001; upper MGL: r=0.438, P<=0.001; lower MGL: r=0.407, P<=0.001). Average
      LLT in non-obstructive MGD EDE, was correlated with meibomian expressibility and
      Oxford staining (r=-0.396, P=0.002; r=-0.461, P<=0.001). The efficiency of
      combining average LLT and TMH was optimal, with a sensitivity of 80.2% and a
      specificity of 74.1%. Obstructive MGD EDE patients had an average LLT>=69 nm and
      TMH>=0.25 mm, while non-obstructive MGD EDE patients had an average LLT<69 nm and
      TMH<0.25 mm. CONCLUSION: Obstructive MGD EDE and non-obstructive MGD EDE have
      significantly different clinical characteristics. Combining average LLT and TMH
      measurements enhanced their reliability for differentiating these two subtypes
      and provided guidance for offering more precise treatments for EDE subtypes.

PMID- 30225225
TI  - Eye reflux: an ocular extraesophageal manifestation of gastric reflux.
AB  - AIM: To suspect laryngopharyngeal reflux (LPR) in patients with ocular surface
      disease (OSD). METHODS: The present study evaluated a group of subjects with OSD
      assessing the Ocular Surface Disease Index (OSDI) and the Reflux Symptom Index
      (RSI) to detect patients with suspected LPR and define a possible relationship
      between tests. RESULTS: Two hundred and ninety subjects (175 females, mean age:
      60.41+/-15.68y) were consecutively visited at ophthalmologist offices. One
      hundred and one (34%) patients had pathological RSI (>13) and consequently a
      suspected LPR. CONCLUSION: The current study shows that suspected LPR may be
      common (34%) in patients with OSD and a suspected LPR may be considered in OSD
      patients when RSI score is >13 and OSDI score is >42.

PMID- 30225226
TI  - Investigation of possible risk factors in the development of seasonal allergic
      conjunctivitis.
AB  - AIM: To analyze the possible risk factors in the development of seasonal allergic
      conjunctivitis (SAC) through an evaluation of skin allergy tests and data
      obtained from questionnaires. METHODS: The study included a total of 75 SAC
      patients and 71 control subjects without SAC diagnosis who were admitted to the
      Abant Izzet Baysal University Medical Faculty Ophthalmology Clinic between March
      2016 and December 2016. Skin prick tests were performed for all participants.
      Serum levels of total IgE and 25-OH vitamin D were also measured. In the tear,
      total IgE levels were measured. Moreover, possible risk factors for the onset of
      SAC (smoking, paracetamol exposure, vitamin D supplementation and environmental
      factors etc.) were examined for all patients by both prenatal and postnatal
      aspects. RESULTS: The patients with SAC were found to have a history of maternal
      paracetamol exposure during the prenatal period. Likewise, in the same patient
      group, the duration of postnatal vitamin D supplementation was shorter (P<0.001).
      However, no significant correlation was found between SAC and maternal antibiotic
      exposure, maternal smoking, the mode of delivery and birth weight, as well as
      presence of pets. Moreover, patients with SAC were more likely to have asthma,
      allergic rhinitis and oral allergy syndrome. We have also found that SAC
      patients' mothers and siblings were more likely to have allergic conjunctivitis.
      Likewise, their fathers were more likely to have allergic rhinitis. CONCLUSION:
      Prenatal maternal paracetamol exposure and shorter duration of vitamin D
      supplementation in the postnatal period may play a role in development of SAC.
      Therefore prevention of unnecessary gestational paracetamol intake and vitamin D
      supplementation during infancy could potentially reduce the onset and development
      of SAC.

PMID- 30225228
TI  - Multimodal imaging in acute retinal ischemia: spectral domain OCT, OCT
      angiography and fundus autofluorescence.
AB  - AIM: To describe retinal findings of various imaging modalities in acute retinal
      ischemia. METHODS: Fluorescein angiography (FA), spectral domain optical
      coherence tomography (SD-OCT), OCT-angiography (OCT-A) and fundus
      autofluorescence (FAF) images of 13 patients (mean age 64y, range 28-86y) with
      acute retinal ischemia were evaluated. Six suffered from branch arterial
      occlusion, 2 had a central retinal artery occlusion, 2 had a combined
      arteriovenous occlusions, 1 patient had a retrobulbar arterial compression by an
      orbital haemangioma and 2 patients showed an ocular ischemic syndrome. RESULTS:
      All patients showed increased reflectivity and thickening of the ischemic retinal
      tissue. In 10 out of 13 patients SD-OCT revealed an additional highly reflective
      band located within or above the outer plexiform layer. Morphological
      characteristics were a decreasing intensity with distance from the fovea,
      partially segmental occurrence and manifestation limited in time. OCT-A showed a
      loss of flow signal in the superficial and deep capillary plexus at the affected
      areas. Reduced flow signal was detected underneath the regions with retinal
      edema. FAF showed areas of altered signal intensity at the posterior pole. The
      regions of decreased FAF signal corresponded to peri-venous regions. CONCLUSION:
      Multimodal imaging modalities in retinal ischemia yield characteristic findings
      and valuable diagnostic information. Conventional OCT identifies
      hyperreflectivity and thickening and a mid-retinal hyperreflective band is
      frequently observed. OCT-A examination reveals demarcation of the ischemic
      retinal area on the vascular level. FAF shows decreased fluorescence signal in
      areas of retinal edema often corresponding to peri-venous regions.

PMID- 30225227
TI  - GSTM1-null and GSTT1-active genotypes as risk determinants of primary open angle
      glaucoma among smokers.
AB  - AIM: To evaluate glutathione transferase theta 1 and mu 1 (GSTT1 and GSTM1)
      polymorphisms as determinants of primary open angle glaucoma (POAG) risk,
      independently or in combination with cigarette smoking, hypertension and diabetes
      mellitus. METHODS: A case-control study with 102 POAG patients and 202 age and
      gender-matched controls was carried out. Multiplex-polymerase chain reaction
      method was used for the analysis of GSTM1 and GSTT1 polymorphisms. The
      differences between two groups were tested by the t-test or chi2 test. Logistic
      regression analysis was used for assessing the risk for disease development.
      RESULTS: The presence of GSTM1-null genotype did not contribute independently
      towards the risk of POAG. However, individuals with GSTT1-active genotype were at
      almost two-fold increased risk to develop glaucoma (P=0.044) which increased up
      to 4.36 when combined with GSTM1-null carriers (P=0.024). When glutathione
      transferase (GST) genotypes were analyzed in association with cigarette smoking,
      hypertension and diabetes, only carriers of GSTT1-active genotype had
      significantly increased risk of POAG development in comparison with GSTT1-null
      genotype individuals with no history of smoking, hypertension and diabetes,
      respectively (OR=3.52, P=0.003; OR=10.02, P<0.001; OR=4.53, P=0.002). CONCLUSION:
      The results obtained indicate that both GSTM1-null and GSTT1-active genotypes are
      associated with increased POAG risk among smokers, suggesting potential gene
      environment interaction in glaucoma development.

PMID- 30225229
TI  - Bimodal imaging of proliferative diabetic retinopathy vascular features using
      swept source optical coherence tomography angiography.
AB  - AIM: To categorize neovessels morphology and to detect response to anti
      angiogenic therapy by using structural and angiographic modes of swept source
      optical coherence tomography (SS-OCT). METHODS: Thirty-two eyes with neovessels
      at disc (NVD) and neovessels elsewhere (NVE) - as diagnosed by fluorescein
      angiography- were included. Cross sectional OCT images of disc and macular
      regions were registered to enface OCT angiography (OCTA), B-scan blood flow over
      lay and density maps. Three eyes received anti-angiogenic treatment. RESULTS: Pin
      point registration of cross-sectional OCT and OCTA images differentiated active
      NVD with vascular elements from fibrous or equivalent fibrovascular elements. En
      face images delineated NVE as vascular tufts or area of filling while cross
      sectional images differentiated NVE from microvascular intraretinal abnormality
      (IRMA). All cases were associated with enlargement of foveal avascular zone and
      or areas of capillary non perfusion. Regressed NVD appeared as ghost vessel or
      pruned vascular loops after injection. CONCLUSION: Structural and angiographic
      modes of SS-OCT can detect, characterize and categorize the pattern of wide
      spectrum of neovessels based on blood flow data and density maps. It is
      potentially useful to detect ischemic changes in the vascular bed and regression
      of NVD after therapeutic regimens providing substitute for invasive techniques.

PMID- 30225230
TI  - Comparison of one and three initial monthly intravitreal ranibizumab injection in
      patients with macular edema secondary to branch retinal vein occlusion.
AB  - AIM: To compare three initial monthly intravitreal ranibizumab (IVR) injections
      followed by pro re nata (PRN) dosing with one initial monthly IVR injections
      followed by PRN dosing for macular edema (ME) secondary to branch retinal vein
      occlusion (BRVO). METHODS: Forty-two eyes of 42 patients who had IVR injections
      for BRVO were retrospectively studied. Eighteen eyes received 1 initial IVR
      injection (1+PRN group) and 24 eyes received 3 monthly IVR injections (3+PRN). At
      1, 3, 6 and 12mo; spectral-domain optical coherence tomography (SD-OCT) was
      performed. Central macular thickness (CMT), the integrity of the external
      limiting membrane (ELM), the presence of subretinal fluid, cyst size, the
      presence of inner segment/outer segment (IS/OS) defect were determined. RESULTS:
      At baseline the mean CMT was 521.3+/-153.2 um in the 3+PRN group while it was
      438.1+/-162.4 um in 1+PRN group. At the final visit, mean CMT was 278.3+/-87.8 um
      in the 3+PRN group and 285.2+/-74.2 um in the 1+PRN group (P=0.079). The changes
      in CMT over the entire study period were also comparable in both groups (243+/
      160 um in the 3+PRN group, and 152.9+/-175.3 um in the 1+PRN group; P=0.090). At
      baseline, best-corrected visual acuity (BCVA) was 0.92+/-0.60 logarithm of the
      minimal angle of resolution (logMAR) in the 3+PRN group, while it was 0.72+/-0.46
      logMAR in the 1+PRN group. Final BCVA was 0.42+/-0.55 logMAR in the 3+PRN group
      and 0.38+/-0.50 logMAR in the 1+PRN group (P=0.979). Additionally, the BCVA
      changes from baseline to final visit were not significantly different (-0.50+/
      0.45 logMAR in the 3+PRN group, and -0.33+/-0.39 logMAR in the 1+PRN group;
      P=0.255). CONCLUSION: No significant differences in the anatomical or functional
      results are found between 3+PRN and 1+PRN regimens in the patients receiving
      ranibizumab for ME secondary to BRVO. Intact IS/OS and baseline BCVA are good
      predictor of the visual gain, while baseline CMT is a good predictor of the
      anatomical gain.

PMID- 30225231
TI  - A clinicopathological study on IgG4-related ophthalmic disease.
AB  - AIM: To investigate clinicopathological features of immunoglobulin G4-related
      ophthalmic disease (IgG4-ROD), and analyze the recurrence rates following
      systemic corticosteroid administration. METHODS: We retrospectively searched
      clinical features, laboratory and histological findings based on the medical
      records of 21 patients with IgG4-ROD. All the patients examined in this study
      underwent surgical resection in the ocular adnexal lesions and underwent
      histological evaluation. This study further investigated clinical and
      histopathological features of 15 patients who received systemic corticosteroid
      after the resection. RESULTS: The mean age of the patients consisting of 7 males
      (33%) and 14 females (67%) was 61y. Fourteen patients were diagnosed as
      definitive, and 2 and 5 patients were probable and possible IgG4-ROD,
      respectively. Eyelid swelling was an initial symptom in 11 patients (52%) who did
      not show systemic involvements at a diagnosis. Fifteen patients received systemic
      corticosteroid administration, and all showed remission of inflammation. Among
      them, 10 patients did not recur, whereas 5 patients (33%) recurred during
      tapering. There were no significant difference between patients with or without
      recurrence in clinicopathological features. CONCLUSION: In this study, female
      patients are more predominant in IgG4-ROD. While inflammation recurs in one-third
      of patients, this study do not identify factors associated with recurrence after
      systemic corticosteroid administration.

PMID- 30225232
TI  - Trends and characteristics of congenital ectopia lentis in China.
AB  - AIM: To elucidate the trends and characteristics of congenital ectopia lentis
      (CEL) in southern China. METHODS: CEL patients from China admitted to Zhongshan
      Ophthalmic Center (ZOC) from January 2006 to December 2015 were recruited in our
      study. Residence, gender, hospitalization time, age at surgery, and the presence
      of other ocular abnormalities and system disease were statistically analyzed in
      different subgroups. RESULTS: Four hundred and thirty-seven hospitalizations (306
      in-patients) diagnosed with CEL from a total of 283 308 hospitalizations were
      identified, which accounted for 0.15% of the total in-patients. Of the identified
      CEL in-patients, the total ratio of boys to girls was 2.22:1. Based on a subgroup
      analysis according to age, patients aged 12-18 years old constituted the highest
      proportion (31.70%) of all hospitalized CEL patients, and those 0-3 year old
      constituted the lowest proportion (8.82%) of the total number. The number of CEL
      increased from 18 to 72 and the hospital based prevalence increased from 8.60% to
      18.10% from 2006 to 2015, and the average age at surgery decreased from 9 years
      old in 2006 to 7.6 years old in 2015. CONCLUSION: The results reveal upward
      trends in both the number of CEL hospitalizations and hospital based prevalence
      of CEL in this 10-year study period, but a reduction in the age at surgery, which
      may reflect the increase of public awareness of children's eye care in China.

PMID- 30225233
TI  - Research progress on the role of connective tissue growth factor in fibrosis of
      diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is one of the most important types of diabetic
      microangiopathy, which is a specific change of fundus lesions and is one of the
      most serious complications of diabetes. When DR develops to proliferative DR, the
      main factors of decreasing vision, and even blindness, include retinal detachment
      and vitreous hemorrhage caused by contraction of blood vessels by fiber membrane.
      Recent studies reported that the formation of fiber vascular membrane is closely
      related to retinal fibrosis. The connective tissue growth factor (CTGF) is a
      cytokine that is closely related to DR fibrosis. However, its mechanism is poorly
      understood. This paper summarizes the recent studies about CTGF on DR fibrosis
      for a comprehensive understanding of the role and mechanism of CTGF in PDR.

PMID- 30225234
TI  - Application of artificial intelligence in ophthalmology.
AB  - Artificial intelligence is a general term that means to accomplish a task mainly
      by a computer, with the least human beings participation, and it is widely
      accepted as the invention of robots. With the development of this new technology,
      artificial intelligence has been one of the most influential information
      technology revolutions. We searched these English-language studies relative to
      ophthalmology published on PubMed and Springer databases. The application of
      artificial intelligence in ophthalmology mainly concentrates on the diseases with
      a high incidence, such as diabetic retinopathy, age-related macular degeneration,
      glaucoma, retinopathy of prematurity, age-related or congenital cataract and few
      with retinal vein occlusion. According to the above studies, we conclude that the
      sensitivity of detection and accuracy for proliferative diabetic retinopathy
      ranged from 75% to 91.7%, for non-proliferative diabetic retinopathy ranged from
      75% to 94.7%, for age-related macular degeneration it ranged from 75% to 100%,
      for retinopathy of prematurity ranged over 95%, for retinal vein occlusion just
      one study reported ranged over 97%, for glaucoma ranged 63.7% to 93.1%, and for
      cataract it achieved a more than 70% similarity against clinical grading.

PMID- 30225235
TI  - A novel NF1 frame-shift mutation c.703_704delTA in a Chinese pedigree with
      neurofibromatosis type 1.
AB  - We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of
      neurofibromatosis type 1 (NF1). Three members of this family were NF1 patients
      presenting with different clinical phenotypes and the others were asymptomatic.
      Exons of NF1 were amplified by polymerase chain reaction, sequenced, compared
      with a reference database. One novel NF1 frame-shift mutation c.703_704delTA,
      which resulted in a premature stop signal at codon 720 and the synthesis of
      truncated, was revealed. This mutation segregated with the NF1 members is likely
      responsible for the pathogenesis of NF1 in the family.

PMID- 30225236
TI  - Retinal detachment in a boy with Gaucher disease.

PMID- 30225237
TI  - Chronic ocular GVHD: limbal and conjunctival stem cell allografts from the same
      hematopoietic stem cell donor.

PMID- 30225238
TI  - Ocular syphilis: resurgence of an old disease in modern Malaysian society.

PMID- 30225239
TI  - The role of M-health applications in the fight against Alzheimer's: current and
      future directions.
AB  - Background: Alzheimer's disease has become a very significant problem in the
      current era that is very likely to worsen due to increasing life expectancy. The
      enormous potential of smart mobile devices has attracted researchers and medical
      practitioners alike to develop and provide M-health solutions for Alzheimer's. In
      this paper, we explore, analyze and investigate the works that have attempted to
      develop M-health applications for Alzheimer's over the last 10 years in order to
      highlight current and future directions, which it is hoped will assist medical
      practitioners and researchers to provide more solutions for fighting Alzheimer's.
      Methods: A systematic review approach was used in this study. Google Scholar is
      considered for searching the published papers for academic mobile applications
      and Google PlayStore is considered for non-academic mobile applications. More
      than 900 titles of various papers were reviewed. The selection of the papers was
      dictated by a set of inclusion and exclusion criteria. Results: Current
      directions are identified by presenting the services and functions that are
      provided by M-health applications for Alzheimer's patients and the technologies
      that are used to do so. Current services are classified into four groups and the
      future directions for each of these groups are presented. Conclusions: Numerous M
      health applications that fight against Alzheimer's have been surveyed and
      analyzed by using scientific methodology in which inclusion and exclusion
      criteria have been used. Based on this analysis, we were able to present the
      current research foci and define potential future research directions.

PMID- 30225240
TI  - Step-by-Step: a new WHO digital mental health intervention for depression.
AB  - The World Health Organization is developing a range of interventions, including
      technology supported interventions, to help address the mental health treatment
      gap, particularly in low and middle-income countries. One of these, Step-by-Step,
      is a guided, technology supported, intervention for depression. It provides
      psychoeducation and training in behavioural activation through an illustrated
      narrative with additional therapeutic techniques such as stress management (slow
      breathing), identifying strengths, positive self-talk, increasing social support
      and relapse prevention. Step-by-Step has been designed so that it can be adapted
      for use in settings with different cultural contexts and resource availability
      and to be meaningful in communities affected by adversity. This paper describes
      the process of developing Step-by-Step and highlights particular design features
      aimed at increasing feasibility of implementation in a wide variety of settings.

PMID- 30225241
TI  - The impact of net neutrality on digital health.

PMID- 30225242
TI  - Prevalence and Associated Factors of Depression among Orphan Adolescents in Addis
      Ababa, Ethiopia.
AB  - Background: Orphan adolescents are a special group of people who are generally
      deprived and prone to develop psychiatric disorder even if reared in a well-run
      institution. Objective: To assess the prevalence and associated factors of
      depression among orphan adolescents living in Addis Ababa orphan centers, Addis
      Ababa, Ethiopia. Method: A cross-sectional study was conducted in 2016 among 453
      orphan adolescents in Ethiopia. All orphan adolescents who were living in the
      selected orphan centers were included in the study. The data was collected by
      interviewing the orphan adolescents at the orphan center by using a structured
      questionnaire. Kocher adolescent depression scale and MSPSS scale were used to
      measure orphan level of depression and their perceived social support. After
      appropriate coding, the collected data had been entered into EPI info version 7
      and it was exported to SPSS version 20 for further analysis. The OR with 95% CI
      was used to measure association and p value < 0.05 was used as statistically
      significant value in multivariable binary logistic regressions. Result: The
      overall prevalence of depression among the orphan adolescents was found to be
      36.4%. The majority of the respondents, 302 (66.7%), were within the age range of
      15-19 years. Perceived social support (OR 5.86; 95% CI 3.47, 9.91), community
      discrimination (OR 2.68; 95% CI 1.58, 4.56), length of stay (OR 1.90; 95% CI
      1.08, 3.35), age of entrance (OR 2.21; 95% CI 1.32, 3.69), and presence of
      visitors (OR 3.62; 95% CI 2.06, 6.37) were the main variables associated with
      depression. Conclusion: The prevalence of depression among orphan adolescents was
      found to be high. Low level of social support, higher length of stay, community
      discrimination, the presence of visitors, and younger age of entrance were
      statistically significant variables to develop depression.

PMID- 30225243
TI  - Epidemiology of Depression and Associated Factors among Asthma Patients in Addis
      Ababa, Ethiopia.
AB  - Background: Depression in asthma patients can cause worsening of respiratory
      symptoms. Addressing mental illness in those with asthma improves asthma
      outcomes. This study aimed to assess the epidemiology of depression and
      associated factors among asthma patients attending government hospitals in
      Ethiopia. Methods: Institutional based cross-sectional study was conducted on
      patients with asthma at three governmental hospitals of Addis Ababa from June to
      July 2017. Patient health questionnaire (PHQ-9) depression scale was used to
      assess prevalence of depression among asthmatic patients. The data were entered
      and analyzed using SPSS version 20 statistical software. Binary logistic
      regression analysis was conducted to identify associated factors for depression.
      To indicate the strength of association, odds ratios (OR) and 95% confidence
      intervals (95% CI) were used. Result: A total of 405 participants were enrolled
      in the study giving an overall response rate of 96%. The respondents had mean age
      of 54.46 and standard deviation (SD) of 10.01 years. About 273 (67.4%) were
      females. The prevalence of depression among asthma patients was 85 (21%). The
      odds of developing depression among single asthma patients were increased by 1.63
      with 95% CI [1. 8, 3.493]. Depression among asthma patients who had comorbid
      cardiac illness was 6.2 times higher than those who do not have at CI [1.145,
      24.109]. The prevalence of depression among uncontrolled asthma patients was 8
      times higher than those with well-controlled asthma at CI [1.114, 19.025].
      Conclusion: One-fifth of asthmatic patients were experiencing depression.
      Uncontrolled asthma, comorbid cardiac illness, and single patients were important
      predictors of depression among asthmatic patients. Proper control of asthmatic
      attack and cardiac illnesses is very important to reduce the burden of
      depression.

PMID- 30225244
TI  - Transcriptome Analysis of Rainbow Trout (Oncorhynchus mykiss) Eggs Subjected to
      the High Hydrostatic Pressure Treatment.
AB  - High hydrostatic pressure (HHP) causes depolymerization of the spindle
      microtubules. HHP applied to fish eggs prevents extrusion of the second polar
      body and inhibits the first cell cleavage, and it is used to produce triploids
      and diploid gynogenetic and androgenetic individuals. HHP has been also found to
      affect biomolecules including nucleic acids, and it may be presumed that HHP
      administered to the rainbow trout (Oncorhynchus mykiss) eggs disturbs cytoplasmic
      maternal RNA indispensable for the early embryogenesis. To verify this
      assumption, quality and quantity of RNA extracted from the rainbow trout eggs
      subjected to the high hydrostatic pressure shock were analyzed. Provided results
      exhibited that maternal transcriptome was resistant to a three-minute exposure to
      65.5 MPa of HHP treatment. Some trend showing increase of the RNA integrity was
      observed in the HHP-treated eggs; however, the difference was not statistically
      significant. Alterations in the expression profiles in the rainbow trout eggs
      subjected to HHP were also negligible. Greater differences in the maternal gene
      expression were observed between eggs from different clutches than between HHP
      treated and untreated eggs from the same clutch. It may be assumed that exposure
      to HHP shock was too short to modify significantly maternal transcripts in the
      rainbow trout eggs.

PMID- 30225245
TI  - Antioxidant and Anticancer Roles of a Novel Strain of Bacillus anthracis Isolated
      from Vermicompost Prepared from Paper Mill Sludge.
AB  - Mass production of vermicompost using suitable species of earthworms and
      selecting target organic waste materials has appeared to be a great development
      in the realm of biotechnological research for the sustainable eco-management.
      Although, for the bioconversion of organic wastes to vermicompost, suitable
      earthworm species play major roles, a hoard of bacterial assemblages by virtue of
      production of different enzymes facilitate the process of vermicomposting. The
      present study has documented the roles of vermicompost associated bacteria in
      combating, preventing, and controlling of cancer so as to open a new vista not
      only in the field of vermitechnology but also on biomedical research. Earthworms'
      associated bacterial metabolic products having their unique physicochemical
      excellence have gained importance due to their roles as a facilitator of
      apoptosis (programed cell death in a MCF-7 cell line). The antioxidant and
      anticancer activities of ethyl acetate extracts' of vermicompost associated
      bacterium Bacillus anthracis were undertaken by antioxidant assay which revealed
      maximum DPPH radical scavenging effect (75.79 +/- 5.41%) of the extracts' at 9 00
      MUg ml-1. Furthermore, the crude extracts obtained from the same bacteria were
      found to decrease the activity of SOD (superoxide dismutase) with the increase in
      doses. MTT assay showed potent cytotoxic activity against human breast
      adenocarcinoma cells (MCF-7) with the IC50 value of 46.64 +/- 0.79 MUg ml-1. It
      was further confirmed through Hoechst 33258 staining of nuclear fragmentation
      assay and DNA fragmentation analysis. Western blotting test has confirmed a
      downregulation of Akt upon application of crude extracts. Increase of SOD
      activity along with decrease of Akt level reflects that the mode of action is
      entirely PI-3K dependent. This study tends to indicate that B. anthracis isolated
      from vermicompost could be potentially explored for the development of new
      therapeutic agents, especially against cancer.

PMID- 30225246
TI  - Antibacterial Activity of Chalcone and Dihydrochalcone Compounds from Uvaria
      chamae Roots against Multidrug-Resistant Bacteria.
AB  - This study presents antimicrobial properties of Uvaria chamae roots, commonly
      used for the treatment of various infections in south Benin. Their constituents
      were extracted and then fractionated in order to isolate the active ingredients.
      Antimicrobial susceptibility tests were performed against several multidrug
      resistant bacteria using the Mueller Hilton well agar diffusion method. Results
      showed that ethanol extracts were highly active against Gram-positive cocci. This
      activity was more extensive than that measured from conventional broad-spectrum
      antibiotics. Indeed, vancomycin-resistant enterococcus (VRE) and methicillin
      resistant Staphylococcus aureus (MRSA) strains were all sensitive to this root
      extract. The aim of this study was to link the antimicrobial activity of the root
      to chemical structures. The ion mobility mass spectrometry analysis revealed for
      the first time the presence of ten chalcone and dihydrochalcone structures
      responsible for the antimicrobial activity of Uvaria chamae ethanol extracts. Two
      structures were described here for the first time in these roots. These findings
      confirm and justify the medical properties of these roots used as a traditional
      medicine.

PMID- 30225248
TI  - Musculoskeletal Disorders: Prevalence and Associated Factors among District
      Hospital Nurses in Haiphong, Vietnam.
AB  - Background: Musculoskeletal disorders (MSDs) are a major occupational health
      problematic among healthcare workers, and the prevalence is especially high among
      nurses. In high income countries, the prevention of MSDs is an occupational
      health priority. But in Vietnam, there is no data available among health
      professionals. Objectives: To determine the prevalence and associated factors of
      musculoskeletal disorders among district hospital nurses in Haiphong city.
      Material and Methods: A cross-sectional study was conducted on 1179 nurses
      working in 15 district hospitals using the Standardized Nordic Questionnaire.
      Results: A very high prevalence of MSDs in the past 12 months (74.7%) and during
      the last 7 days (41.1%), with the two most common sites being the low back
      (44.4%) and neck (44.1%), was found; 37.8% complained that MSDs symptoms limit
      their work. When analyzing factors related to MSDs, the results showed that women
      were 2.1 times more likely to develop MSDs than men; people with a previous
      history of MSDs were more likely to develop MSDs symptoms in the past 12 months
      than those with no history (OR = 7.1); nurses with symptoms of psychological
      distress and frequent absenteeism in the workplace had a higher prevalence of
      MSDs compared to the rest (p<0.001). Conclusions: Due to the high prevalence of
      MSDs among nurses in district hospitals in Haiphong, preventive actions are
      needed to improve the working conditions and to raise the awareness of nurses
      about MSDs prevention.

PMID- 30225247
TI  - Protective Effects of Benzoic Acid, Bacillus Coagulans, and Oregano Oil on
      Intestinal Injury Caused by Enterotoxigenic Escherichia coli in Weaned Piglets.
AB  - The use of antibiotics as growth promoters in feed has been fully or partially
      banned in several countries. The objective of this study was to investigate the
      effects of benzoic acid (A), bacillus coagulans (B) and oregano oil (O) combined
      supplementation on growth performance and intestinal barrier in piglets
      challenged with enterotoxigenic Escherichia coli (ETEC). Thirty piglets were
      randomly assigned to 6 treatments: (1) nonchallenged control (CON); (2) ETEC
      challenged control (ETEC); (3) antibiotics + ETEC (AT); (4) A + B + ETEC (AB);
      (5) A + O + ETEC (AO); (6) A + B + O + ETEC (ABO). On day 22, piglets were orally
      challenged with ETEC or saline. The trial lasted 26 days. Dietary AO and ABO
      inhibited the reduction of growth performance and the elevation of diarrhoea
      incidence in piglets induced by ETEC (P<0.05). AB, AO, and ABO prevented the
      elevation of serum TNF-alpha and LPS concentrations in piglets induced by ETEC
      (P<0.05). ABO alleviated the elevation of TNF-alpha and IL-1beta concentrations
      and the reduction of sIgA level in jejunal mucosa induced by ETEC (P<0.05).
      Furthermore, ABO upregulated mRNA expressions of Claudin-1 and Mucin2 (P<0.05),
      downregulated mRNA abundances of TLR4 and NOD2 signaling pathways related genes
      in jejunal mucosa (P<0.05), and improved the microbiota in jejunal and cecal
      digesta (P<0.05) compared with ETEC group. These results indicated that benzoic
      acid, bacillus coagulans, and oregano oil combined supplementation could improve
      growth performance and alleviate diarrhoea of piglets challenged with ETEC via
      improving intestinal mucosal barrier integrity, which was possibly associated
      with the improvement of intestinal microbiota and immune status. The combination
      of 3000 g/t benzoic acid + 400 g/t bacillus coagulans + 400 g/t oregano oil
      showed better effects than other treatments in improving growth performance and
      intestinal health of piglets, which could be used as a viable substitute for
      antibiotic.

PMID- 30225249
TI  - An Investigation on the Therapeutic Effect of Thymosin beta4 and Its Expression
      Levels in Streptozotocin-Induced Diabetic Mice.
AB  - Thymosin beta4 (Tbeta4) treatment was known to show the potential therapeutic
      effects on diabetic complications. This study was performed to determine if
      Tbeta4 expression is changed in both serum and tissues under diabetic conditions
      and can be a serum biomarker. Type 1 diabetic mice were induced in C57/BL6J mice
      by intraperitoneal injection of streptozotocin (STZ) at a dose of 50 mg/kg body
      weight. The mice were sacrificed at 16 weeks after STZ injection. Tissues and
      plasmas were obtained to determine the expression levels of Tbeta4 using ELISA,
      real time RT-PCR, and immunohistochemistry. The average serum glucose level was
      increased to approximately 400 mg/dL beginning 2 weeks after the five injections
      of STZ and lasting for at least 13 weeks until sacrifice. The plasma and tissue
      levels of Tbeta4 in the age-matched control mice were not significantly different
      from those of the diabetic mice. In conclusion, the Tbeta4 expression level in
      the plasmas and tissues of diabetic mice was not affected by diabetic conditions.
      It indirectly suggests that the therapeutic effect of Tbeta4 on diabetic
      complications is due to its regenerative effects on damaged tissue but not to the
      changed expression level of Tbeta4 in plasma and tissues of diabetes.

PMID- 30225250
TI  - Odontogenic Abscess-Related Emergency Hospital Admissions: A Retrospective Data
      Analysis of 120 Children and Young People Requiring Surgical Drainage.
AB  - Introduction: Even today, despite medical progress and intensive health
      education, odontogenic infections leading to surgical intervention and
      hospitalization are common in children and young people. The aim of this study
      was to give a detailed overview of clinical and economic data on children and
      young people treated and hospitalized due to an odontogenic abscess at a tertiary
      university hospital. Methods: A single-center retrospective analysis of patients
      under the age of 18 years who were hospitalized and surgically treated under
      local or general anesthesia for an odontogenic abscess during a period of 24
      months was performed. Results: A total of 120 patients (77 males; 43 females)
      within the observation period of 2 years were included. The mean age was 6.3
      years (ranging from 1 to 17 years). The most frequent diagnosis was a canine
      fossa abscess (n = 52; 43.3%) and the left primary maxillary first molar could be
      identified as the most frequent source of infection. The average length of
      hospital stay was 1.82 days (ranging from 0 to 8 days). The duration was
      significantly correlated with the kind of abscess diagnosed (p < 0.001) and the
      duration of the surgical intervention in patients who were treated under general
      anesthesia (rho = 0.259, p = 0.005). A statistically significant relationship was
      observed between the kind of abscess and cost (p < 0.001). Conclusion: The length
      of hospital stay was significantly correlated with the kind of abscess diagnosed.
      The left primary maxillary first molar could be identified as the most frequent
      source of infection. A statistically significant relationship was observed
      between the kind of abscess and cost.

PMID- 30225251
TI  - Actinomyces and Alimentary Tract Diseases: A Review of Its Biological Functions
      and Pathology.
AB  - Actinomyces are nonmotile, filamentous, Gram-positive bacteria that cause
      actinomycosis in immunodeficiency patients. Although the prognosis of
      actinomycosis is good, the diagnosis of actinomycosis is quite difficult. Recent
      studies on actinomycosis have shown that Actinomyces play an important role in
      various biological and clinical processes, such as the formation of dental plaque
      and the degradation of organics in the gastrointestinal tract. Here, the
      distribution of Actinomyces in the digestive tract, and different biological
      effects of actinomycosis, and its clinical association with inflammatory diseases
      are discussed. Furthermore, an overview of the most commonly used treatment
      methods and drugs used to treat Actinomyces infected alimentary canal diseases is
      presented.

PMID- 30225252
TI  - Assessment of the Use and Status of New Drug Information Centers in a Developing
      Country, Ethiopia: The Case of Public University Hospital Drug Information
      Centers.
AB  - Introduction: Drug information center (DIC), in most cases, is part and parcel of
      pharmacy service established as a unit that deals with offering recent, balanced,
      truthful facts about drugs to the public, patients, and health care
      professionals. Objective: To assess the query receiving and response trends by
      the drug information centers (DICs) found in main university affiliated teaching
      health care institutes in Ethiopia. Settings: The drug information centers
      located in Mekelle, Gondar, Jimma, Tikur Anbessa Specialized University
      Hospitals, and St. Peter Public Hospital, Ethiopia. Methods: It employed
      analytical, descriptive (cross-sectional), and retrospective methods. The study
      was performed from June to August, 2015. All the available documented data were
      gathered with the help of checklist and questionnaire (self-administered).
      Results: A total of 439 queries submitted to the DICs during their active service
      period were included in this study of which 407 were found to be suitable for
      this assessment. The highest inquiries had come from public hospitals (60 %) from
      health care workers (95.1 %), out of which pharmacists were the highest (63.57 %)
      submitters, followed by health care students (12.7 %). The major purposes of
      query submission were to improve treatment outcome of patients (33.9 %) and then
      to update the knowledge (25.1 %) although 39.3 % of the queries did not document
      it. The most common requests concern drug interaction (19.7 %) followed by
      therapeutic use (17.8 %) and the major pharmacological group is about
      antimicrobials (23.3 %) followed by antihypertensives (11.4 %). Web sites (31.4
      %) were the most highly used references followed by Micromedex (19.0 %).
      Conclusion: The assessment of the DICs had shown that it is feasible to establish
      and develop DIC services in a developing country setting, Ethiopia. The study
      found that most of the common queries deal with drug interaction, therapeutic
      use, and general product information (most commonly about antimicrobials).

PMID- 30225253
TI  - Osteoporosis and Jaw Abnormalities in Panoramic Radiography of Chronic Liver
      Failure Patients.
AB  - Introduction: Patients with chronic liver failure (CLF) are faced with many
      complications, because this organ is involved in various metabolic activities.
      Hepatic osteodystrophy is one of the major health issues encountered by this
      group of patients. The current study evaluated osteoporosis and bone changes in
      oral panoramic radiographies of cirrhotic patients. Materials and Methods: In
      this study, 138 panoramic views of CLF patients, candidates for liver transplant
      (65 females, 73 males, aged 19-68 years) referred to Shiraz University Dental
      Clinic (Shiraz, Iran) for pretransplant oral examination, were evaluated. Also
      138 healthy individuals (69 females, 69 males, aged 18-70 years) referred to the
      same clinic were examined. Abnormalities such as osteoporosis, pathologic
      radiolucencies, pathologic calcifications, tonsilloliths, condylar degeneration,
      and other findings in the alveolar bones were recorded. Results: Osteoporosis was
      a common finding in CLF patients (p<0.001), and the probability of detecting low
      bone density in the panoramic view was 20.37 times higher among patients than
      healthy subjects. The probability of detecting pathologic jaw radiolucencies was
      8.92 times higher in the case group than in the controls (p<0.001). Other bone
      abnormalities such as condylar degeneration and idiopathic osteosclerosis were
      also more prevalent in CLF patients compared to healthy subjects (p<0.001).
      Conclusion: Cirrhotic patients are prone to osteoporosis of the alveolar bones.
      Also, pathologic jaw radiolucencies as a result of oral infections are more
      prevalent in this group of patients. Routine oral panoramic views are acceptable
      and cost-effective radiographies for use in detecting such abnormalities in the
      alveolar bones as well as overall dental health. These findings also support the
      importance of dental health examinations prior to liver transplantation to reduce
      the risk of organ rejection.

PMID- 30225254
TI  - Synthesis and Evaluation of Biological Activity of New Arylphosphoramidates.
AB  - The synthesis of new substituted arylphosphoramidates is performed in two steps
      through phosphorylation of the corresponding alcohols followed by aminolysis. The
      formation of the desired phosphoramidates depends on the subsequent addition of
      the two alcohols with the amine being added at the last step. The products were
      obtained in 58-95% yields. They were characterized mainly by multinuclear (1H,
      13C, 31P, and 19F) NMR and IR spectroscopy. In addition, the antimicrobial and
      antiacetylcholinesterase activities were evaluated. The results showed
      acetylcholinesterase activity by some compounds, whilst no significant inhibitory
      effect against the tested bacterial strains has been recorded.

PMID- 30225255
TI  - Knowledge, Attitudes, and Hygienic Practices of Boiled Hypocotyls (Borassus
      aethiopum Mart) Vended in the Streets of Cotonou City and Its Outskirts, Benin.
AB  - In Benin, the boiled hypocotyl (Borassus aethiopum Mart) is one of the most
      common street foods consumed for its therapeutic properties. However, the
      knowledge, attitudes, and practices of boiled hypocotyl food sellers are poorly
      known despite the high contamination potential of these street foods. This study
      aimed to determine the knowledge, attitudes, and practices of boiled hypocotyls
      food vendors in the streets of Cotonou and its outskirts. The approach used
      concerned the process of good hygiene and production. Face-to-face interviews of
      300 hypocotyls vendors and producers from Cotonou, Seme, Ouidah, and Abomey
      Calavi were conducted. Concurrently, 200 samples of boiled hypocotyl were
      collected among study vendors. Results showed that all of the interviewed
      population (100%) of this activity are women. They are generally illiterate and
      75% of them have never been to school. Additionally, 76.7% of street boiled
      hypocotyls sellers interviewed were mobile. The microbial profile of the boiled
      hypocotyls showed the lack of control and poor understanding of hygiene rules.
      The processes management also revealed two diagrams processes. The conditions in
      which hypocotyls vendors operate are largely unacceptable from a food safety
      point of view and an effort should be made to provide them with adequate
      infrastructure including potable water. In view of the socioeconomic impact of
      hypocotyl activities in Benin and their role in the unexpected arrival of food
      borne diseases, vendors should be regularly trained in order to prevent outbreaks
      of food-borne illnesses.

PMID- 30225256
TI  - Association between Polymorphisms of Antioxidant Gene (MnSOD, CAT, and GPx1) and
      Risk of Coronary Artery Disease.
AB  - Objective: Reactive oxygen species (ROS) been cited as one of the major causes of
      atherosclerosis and coronary artery disease which are possible agents inducing
      DNA damage. Manganese superoxide dismutase (MnSOD), catalase (CAT), and
      glutathione peroxidase-1 (GPx1) have evolved to address primary defense against
      free radical mediated damage in mitochondria. The aim of this study was to
      delineate the association of MnSOD, CAT, and GPx1 polymorphisms and risk of CAD
      in Taiwan. Methods: We conducted a case-control study with 657 participants
      recruited at a medical center. All subjects were evaluated by noninvasive stress
      test and then quantitative coronary angiography to confirm the diagnosis of CAD.
      447 CAD cases were defined as >50% stenosis of coronary artery and 210 controls
      were stenosed below 50%. Polymorphisms of MnSOD (Val16Ala), CAT (C-262T), and
      GPx1 (Pro198Leu) genes were determined by polymerase chain reaction methods.
      Multivariate logistic regression model was used to calculate the odds ratios
      (ORs) and 95% confidence intervals (CIs). Results: The MnSOD Val/Ala+Ala/Ala
      genotype was significantly associated with an increased risk of CAD compared to
      the Val/Val genotype (OR = 1.86, 95% CI = 1.15-3.01). This polymorphism was also
      associated with the severity of CAD of single and two vessel diseases. The
      corresponding ORs were 2.31 (95% CI = 1.32-4.03) and 1.92 (95% CI = 1.02-3.61),
      respectively. Among cigarette smokers, the harmful genetic effect of MnSOD Ala
      allele on CAD risk was much higher (OR = 2.23, 95% CI = 1.02-4.88). However, the
      interaction between MnSOD genotype and cigarette smoking on CAD risk was not
      significant. No significant association between CAT and GPx1 polymorphisms and
      CAD risk was observed. Conclusion: Our results suggest that MnSOD polymorphism is
      an independent risk factor for susceptibility to CAD in the Chinese population.

PMID- 30225257
TI  - Evolution and Expression Divergence of E2 Gene Family under Multiple Abiotic and
      Phytohormones Stresses in Brassica rapa.
AB  - To understand ubiquitination mechanism, E2s (ubiquitin conjugating enzymes) have
      crucial part as they play a major role in regulating many biological processes in
      plants. Meanwhile, Brassica rapa is an important leafy vegetable crop and
      therefore its characterization along with the expression pattern of E2s under
      various stresses is imperative. In this study, a total of 83 genes were
      identified in B. rapa and were classified into four different classes based on
      domain information. Here, we analyzed phylogenetic relationships, collinear
      correlation, gene duplication, interacting network, and expression patterns of E2
      genes in B. rapa. Furthermore, RT-PCR analysis for 8 multiple abiotic and hormone
      treatments (namely, ABA, GA, JA, BR, PEG, NaCl, and heat and cold stress)
      illustrated striking expression pattern under one or more treatments, speculating
      that these might be stress-responsive genes. The cis-elements and interaction
      network analyses implicate valuable clues of important function of E2 genes in
      development and multiple stress responses in B. rapa. This study will further
      facilitate functional analysis of E2s for improving stress resistance mechanism
      in B. rapa.

PMID- 30225258
TI  - Antibiotics Resistance Genes Screening and Comparative Genomics Analysis of
      Commensal Escherichia coli Isolated from Poultry Farms between China and Sudan.
AB  - Escherichia coli (E. coli) strains, from the gut of animals and humans, harbor
      wide range of drug resistance genes. A comparative study is conducted on the
      intestinal E. coli from fecal samples of healthy chicken from China and Sudan in
      order to monitor the antimicrobial sensitivity pattern. A number of 250 E. coli
      isolates from chicken farms, including 120 from China and 130 from Sudan, were
      isolated and identified. All isolates were subjected to susceptibility tests
      against 10 antibiotics and the distribution of antibiotic resistant genes was
      confirmed by PCR amplification, involving genes such as ampC, tetA, pKD13, acrA,
      ermA, ermB, ermC, tetB, mphA, aadA14, aadA1, aac3-1, and aac3- III. Many isolates
      were found to exhibit resistance against more than one antibiotic. However, the
      Chinese isolates showed more antibiotics resistance and resistance genes compared
      to the Sudanese isolates. For better understanding of the multidrug resistance
      factors, we conducted whole genome analyses of E. coli D107 isolated from China,
      which revealed that the genome possesses multiple resistance genes including
      tetracycline, erythromycin, and kanamycin. Furthermore, E. coli D4 isolate from
      Sudan was more sensitive to antibiotics such as erythromycin, tetracycline, and
      gentamicin. After analysis by RAST and MAUVE, the two strains showed 89% average
      nucleotide identity. However, the genomes mostly differed at the number of
      antibiotics-related genes, as the genome of D107 revealed a considerable number
      of antibiotics resistance genes such as ermA and mphD which were found to be
      absent in D4 genome. These outcomes provided confirmation that the poultry farms
      environment in different countries (China and Sudan) may serve as a potential
      reservoir of antimicrobial resistance genes and also indicated the evolutionary
      differences of strains in terms of resistant genes expression.

PMID- 30225259
TI  - All-Trans Retinoic Acid Enhances Matrix Metalloproteinase 2 Expression and
      Secretion in Human Myeloid Leukemia THP-1 Cells.
AB  - All-trans retinoic acid (ATRA) is an effective drug for the induction therapy of
      acute promyelocytic leukemia. However, the treatment is associated with adverse
      events such as retinoic acid syndrome (RAS) in some patients, whose histologic
      characteristics included organ infiltration by leukemic cells. Matrix
      metalloproteinase 2 (MMP-2) is often upregulated in tumor cells and plays a role
      in tumor cell migration and invasion by degrading the extracellular matrix. In
      this study, we examined the possible modulatory effects of ATRA on MMP-2
      expression and secretion in human myeloid leukemia cell line THP-1. The cells
      were treated with various concentrations of ATRA, and MMP-2 expression and
      secretion were examined. MMP-2 expression and secretion started to increase with
      ATRA concentration as low as 0.1 nM and gradually increased thereafter. Agonists
      of retinoic acid receptor (RAR) or retinoid X receptor (RXR) alone could enhance
      MMP-2 secretion, and RAR or RXR antagonists alone could reverse ATRA-induced MMP
      2 secretion. ATRA increased intracellular calcium ion levels, and a calcium
      channel blocker inhibited ATRA-induced MMP-2 secretion. Dexamethasone suppressed
      ATRA-induced MMP-2 secretion. Our results suggest that ATRA enhances MMP-2
      expression and secretion in human myeloid leukemia THP-1 cells in a calcium ion
      dependent manner through RAR/RXR signaling pathways, and this enhanced expression
      and secretion may be associated with the possible mechanisms of RAS.

PMID- 30225260
TI  - Metronomic Chemotherapy with Vinorelbine Produces Clinical Benefit and Low
      Toxicity in Frail Elderly Patients Affected by Advanced Non-Small Cell Lung
      Cancer.
AB  - Background: Lung cancer is the leading cause of death worldwide. The treatment
      choice for advanced stage of lung cancer may depend on histotype, performance
      status (PS), age, and comorbidities. In the present study, we focused on the
      effect of metronomic vinorelbine treatment in elderly patients with advanced
      unresectable non-small cell lung cancer (NSCLC). Methods: From January 2016 to
      December 2016, 44 patients affected by non-small cell lung cancer referred to our
      oncology day hospital were progressively analyzed. The patients were treated with
      oral vinorelbine 30 mg x 3/wk or 40 mg x 3/wk meaning one day on and one day off.
      The patients were older than 60, stage IIIB or IV, ECOG PS >= 1, and have at
      least one important comorbidity (renal, hepatic, or cardiovascular disease). The
      schedule was based on ECOG-PS and comorbidities. The primary endpoint was
      progression-free survival (PFS). PFS was used to compare patients based on
      different scheduled dosage (30 or 40 mg x3/weekly) and age (more or less than 75
      years old) as exploratory analysis. We also evaluated as secondary endpoint
      toxicity according to Common Toxicity Criteria Version 2.0. Results: Vinorelbine
      showed a good safety profile at different doses taken orally and was effective in
      controlling cancer progression. The median overall survival (OS) was 12 months.
      The disease control rate (DCR) achieved 63%. The median PFS was 9 months. A
      significant difference in PFS was detected comparing patients aged below with
      those over 75, and the HR value was 0.72 (p<0.05). Not significant was the
      difference between groups with different schedules. Conclusions: This study
      confirmed the safety profile of metronomic vinorelbine and its applicability for
      patients unfit for standard chemotherapies and adds the possibility of
      considering this type of schedule not only for very elderly patients.

PMID- 30225261
TI  - Dynamic Three-Dimensional Contrast-Enhanced Ultrasound to Predict Therapeutic
      Response of Radiofrequency Ablation in Hepatocellular Carcinoma: Preliminary
      Findings.
AB  - Background & Aims: To investigate the value of dynamic three-dimensional contrast
      enhanced ultrasound (3D-CEUS) in the assessment of therapeutic response of
      hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA).
      Methods: Forty-two patients (31 men and 11 women; mean age (52.1 +/- 13.1 years))
      with 42 clinical diagnosed HCC lesions (size range 14-48 mm; mean size 28.4 +/-
      9.9 mm) treated by RFA were included. All patients underwent two-dimensional
      contrast-enhanced ultrasound (2D-CEUS) and 3D-CEUS 1 month after treatment. Two
      radiologists assessed the absence (complete response, CR) or presence (residual
      tumor, RT) of any arterially hyperenhancing nodules within or along the margin of
      the treated HCC lesions. Complete response on magnetic resonance (MR) imaging
      acted as standard of reference (SOR). Results: After RFA treatment, 3D-CEUS was
      successfully conducted in 34 HCC lesions. CR was observed on both 2D-CEUS and 3D
      CEUS in 25/42 (59.5%) HCC and RT in 6/42 (14.3%) HCC lesions. In 3/42 (7.1%) HCC
      lesion, RT was documented by SOR and 3D-CEUS, but it was not appreciable at 2D
      CEUS. In 3/42 (7.1%) HCC lesion, the presence of peripheral RT was suspected by
      both 2D-CEUS and 3D-CEUS, but it was not confirmed by SOR. No statistically
      significant difference between 2D-CEUS and 3D-CEUS in depicting either CR or RT
      was found (P = 0.25). Combined with dynamic 3D-CEUS, the diagnostic accuracy was
      improved from 85.7% to 92.9%. Conclusions: 3D-CEUS might be helpful in better
      diagnostic performance in the assessment of therapeutic response of HCC treated
      after RFA.

PMID- 30225262
TI  - Usefulness of Cryoprobe in Office Hysteroscopy for Removal of Polyps and Myomas.
AB  - Hysteroscopy is a gold standard in 21st-century gynaecology for both diagnosis
      and treatment procedures of intrauterine pathologies. Miniaturisation of the
      equipment and better techniques of performing this procedure allowed it to become
      the gold standard. Nevertheless, hysteroscopy has its limitations, which is the
      size of the endometrial polyps or submucous myomas. We have invented a new device
      for the 5Fr working channel hysteroscopes for possessing and resecting
      intrauterine structures: the cryoprobe. The retrospective cryobiopsy study
      presented here was conducted at the Department of Gynaecology and Oncological
      Gynaecology, Military Institute of Medicine in Warsaw, Poland, from October 2017
      to January 2018. Its purpose was to assess the usefulness of the new device in
      office hysteroscopy for the removal of polyps and myomas with a diameter over 10
      mm. Thirteen patients with an initial diagnosis of an endometrial polyp or
      submucous myoma were enrolled in the trial. All procedures took place in day
      surgery settings, with a total resection of the pathological intrauterine
      structure, without complications. The application of the cryoprobe may enhance
      the usefulness of office hysteroscopy, without extending the procedure. The
      cryoprobe efficiency is still under research in a bigger group.

PMID- 30225263
TI  - Exhaled Nitric Oxide and Exhaled Breath Temperature as Potential Biomarkers in
      Patients with Pulmonary Hypertension.
AB  - Background: Pulmonary hypertension (PH) is a progressive fatal disease thus,
      noninvasive prognostic tools are needed to follow these patients. The aim of our
      study was to evaluate fractional exhaled nitric oxide (FeNO) and exhaled breath
      temperature (EBT) values in patients with PH from different causes and to
      correlate them with respiratory functional data. Methods: Twenty-four PH patients
      underwent spirometry, carbon monoxide diffusion (DLCO) test, transthoracic
      echocardiography, right-heart catheterization, and FeNO and EBT measurements.
      Results: We studied 3 groups according to the type of PH: 10 patients with
      pulmonary arterial hypertension (PAH) (group A), 11 patients with PH due to
      chronic obstructive pulmonary disease (COPD) (group B), and 3 patients with PH
      associated with left heart disease (group C). Mean FeNO values tend to be higher
      in group B (15.0 +/- 9.3ppb) compared with other groups (respectively, 9.9 +/-
      5.7 and 8.5 +/- 5.2 ppb in groups A and C; p = 0.271) but no statistical
      significance has been reached. Mean values of alveolar NO concentration (CANO)
      were higher in groups A and B compared to group C (respectively, 16.9 +/- 12.6;
      13.9 +/- 6.8; and 6.7 +/- 2.0 ppb) (p = 0.045). EBT mean values were
      significantly lower in group C when compared with other groups (group C: 29.0 +-
      1.3 degrees C, groups A and B: 30.9 +/- 1.3 and 31.2 +/- 1.2 degrees C,
      respectively: p = 0.041). EBT levels were inversely correlated to mean pulmonary
      artery pressure (PAPm) levels (Spearman coefficient -0.481; p = 0.017).
      Conclusions: eNO, CANO, and EBT have been evaluated in three groups of PH
      patients. Interestingly EBT reduction was correlated with PAPm increase, whereas
      FeNO was higher in COPD patients and CANO in PAH and COPD groups. Further studies
      are needed to clarify EBT, FeNO, and CANO roles as biomarkers in the monitoring
      of patients with PH.

PMID- 30225266
TI  - Three-Dimensional Motion Analysis of the 2nd Cervical Spinous Process at End
      Range Cervical Rotation in Different Scapular Positions Using 3D Digitizer.
AB  - Objective: The study used a 3D digitizer to determine three-dimensional motion
      analysis of the 2nd cervical (C2) spinous process at end range cervical rotation
      with the scapula in different positions. Methods: 30 healthy adults participated
      in this study. Different scapula positions were adopted bilaterally and
      positioned passively at normal resting, depression, adduction, and abduction.
      Under each scapula position, bilateral end range cervical rotation and
      displacement of the C2 spinous process were analyzed by a 3D digitizer. Results:
      Displacement of the C2 spinous process relative to the occiput was significantly
      correlated with range of cervical rotation under all scapular positions (p<0.05).
      However, there were no significant differences between end range cervical
      rotation and displacement of the C2 spinous process relative to the occiput in
      any scapular position. Conclusion: These results suggest that measurement of
      upper cervical mobility using the 3D digitizer is a reliable method that holds
      promise in the evaluation of people with cervical spine disorders.

PMID- 30225265
TI  - RAGE and TLRs as Key Targets for Antiatherosclerotic Therapy.
AB  - Receptor for advanced glycation end-products (RAGE) and toll-like receptors
      (TLRs) are the key factors indicating a danger to the organism. They recognize
      the microbial origin pathogen-associated molecular patterns (PAMPs) or damage
      associated molecular patterns (DAMPs). The primary response induced by PAMPs or
      DAMPs is inflammation. Excessive stimulation of the innate immune system occurs
      in arterial wall with the participation of effector cells. Persistent adaptive
      responses can also cause tissue damage and disease. However, inflammation
      mediated by the molecules innate responses is an important way in which the
      adaptive immune system protects us from infection. The specific detection of
      PAMPs and DAMPs by host receptors drives a cascade of signaling that converges at
      nuclear factor-kappaB (NF-kappaB) and interferon regulatory factors (IRFs) and
      induces the secretion of proinflammatory cytokines, type I interferon (IFN), and
      chemokines, which promote direct killing of the pathogen. Therefore, signaling of
      these receptors' pathways also appear to present new avenue for the modulation of
      inflammatory responses and to serve as potential novel therapeutic targets for
      antiatherosclerotic therapy.

PMID- 30225264
TI  - Complement System and Age-Related Macular Degeneration: Implications of Gene
      Environment Interaction for Preventive and Personalized Medicine.
AB  - Age-related macular degeneration (AMD) is the most common cause of visual loss in
      developed countries, with a significant economic and social burden on public
      health. Although genome-wide and gene-candidate studies have been enabled to
      identify genetic variants in the complement system associated with AMD
      pathogenesis, the effect of gene-environment interaction is still under debate.
      In this review we provide an overview of the role of complement system and its
      genetic variants in AMD, summarizing the consequences of the interaction between
      genetic and environmental risk factors on AMD onset, progression, and therapeutic
      response. Finally, we discuss the perspectives of current evidence in the field
      of genomics driven personalized medicine and public health.

PMID- 30225267
TI  - Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the
      Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats.
AB  - Rosiglitazone is an agonist of peroxisome proliferator-activated receptor- (PPAR
      ) gamma that is principally associated with insulin action. The exact mechanisms
      underlying its insulin-sensitizing action are still not fully elucidated. It is
      well known that adiponectin mostly secreted in adipose tissue is an insulin
      sensitizer. Here, we found that treatment of Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats with rosiglitazone (3 mg/kg, once daily, by oral gavage for 33
      weeks) attenuated the increase in fasting plasma insulin concentrations and the
      index of the homeostasis model assessment of insulin resistance along with the
      age growth and glucose concentrations during an oral glucose tolerance test. In
      addition, the increase in plasma alanine aminotransferase activity,
      concentrations of fasting plasma nonesterified fatty acids and triglyceride, and
      hepatic triglyceride content was also suppressed. The hepatic protein expression
      profile revealed that rosiglitazone increased the downregulated total protein
      expression of insulin receptor substrate 1 (IRS-1) and IRS-2. Furthermore, the
      treatment suppressed the upregulated phosphorylation of IRS-1 at Ser307 and IRS-2
      at Ser731. The results indicate that rosiglitazone ameliorates hepatic and
      systemic insulin resistance, hepatic inflammation, and fatty liver.
      Mechanistically, rosiglitazone suppressed hepatic protein overexpression of both
      phosphorylated nuclear factor- (NF-) kappaBp65 and inhibitory-kappaB kinase
      alpha/beta, a transcription factor that primarily regulates chronic inflammatory
      responses and the upstream NF-kappaB signal transduction cascades which are
      necessary for activating NF-kappaB, respectively. More importantly, rosiglitazone
      attenuated the decreases in adipose adiponectin mRNA level, plasma adiponectin
      concentrations, and hepatic protein expression of adiponectin receptor-1 and
      receptor-2. Thus, we can draw the conclusion that rosiglitazone elicits an
      adiponectin-mediated insulin-sensitizing action at the adipose tissue-liver axis
      in obese rats. Our findings may provide new insights into the mechanisms of
      action of rosiglitazone.

PMID- 30225268
TI  - Effect of a Nurse-Led Diabetes Self-Management Education Program on Glycosylated
      Hemoglobin among Adults with Type 2 Diabetes.
AB  - In recent years, great emphasis has been placed on the role of nonpharmacological
      self-management in the care of patients with diabetes. Studies have reported that
      nurses, compared to other healthcare professionals, are more likely to promote
      preventive healthcare seeking behaviors. The aim of this study was to investigate
      the effectiveness of a nurse-led diabetes self-management education on
      glycosylated hemoglobin. A two-arm parallel-group randomized controlled trial
      with the blinded outcome assessors was designed. One hundred forty-two adults
      with type 2 diabetes were randomized to receive either usual diabetes care
      (control group) or usual care plus a nurse-led diabetes self-management education
      (intervention group). Duration of the intervention was 12 weeks. The primary
      outcome was glycosylated hemoglobin (HbA1c values). Secondary outcomes were
      changes in blood pressure, body weight, lipid profiles, self-efficacy (efficacy
      expectation and outcome expectation), self-management behaviors, quality of life,
      social support, and depression. Outcome measures were assessed at baseline and at
      12-week and 24-week postrandomizations. Patients in the intervention group showed
      significant improvement in HbA1c, blood pressure, body weight, efficacy
      expectation, outcome expectation, and diabetes self-management behaviors. The
      beneficial effect of a nurse-led intervention continued to accrue beyond the end
      of the trial resulting in sustained improvements in clinical, lifestyle, and
      psychosocial outcomes. This trial is registered with IRCT2016062528627N1.

PMID- 30225269
TI  - Perceptions on Diet and Dietary Modifications during Postpartum Period Aiming at
      Attenuating Progression of GDM to DM: A Qualitative Study of Mothers and Health
      Care Workers.
AB  - Background: Gestational diabetes mellitus (GDM) is a global concern. GDM mothers
      have a 7-fold relative risk of developing type 2 diabetes mellitus (T2DM) in
      their later life. User-friendly and culturally acceptable dietary interventions
      can minimize this risk. Therefore, this study aims at exploring the perceptions
      of GDM mothers and health care workers regarding factors that influence
      postpartum dietary practices aimed at attenuating the trajectory from GDM to DM.
      Methods: The study was conducted in selected MOH areas in three districts of Sri
      Lanka. Six focus group discussions were conducted with thirty mothers with a
      history of GDM and six in-depth interviews with six health care workers. The
      phenomenon of interest was to obtain inputs of two stakeholder groups on healthy
      food habits of GDM mothers during the postpartum period. Framework analysis was
      used to analyse the data. Data were coded using the analytical framework,
      abstracted from transcripts, and summarized verbatim in Microsoft Excel in a
      matrix comprised of one row per participant and one column per code. Finally, the
      matrix was reviewed intensely and themes were generated. Results: Overall, seven
      themes emerged from both cases: (1) myths and traditions specific to the
      postpartum period, (2) lack of motivation, (3) time pressure, (4) financial
      barriers, (5) negligence of mothers and families, (6) lack of awareness regarding
      GDM and its postpartum dietary recommendations, and (7) cultural barriers.
      Conclusions: This study provides an insight into the existing knowledge, common
      practices, and attitudes regarding food habits among postpartum mothers with a
      history of GDM. Since the postpartum period is unique, identifying barriers is
      crucial when introducing dietary modification protocols in order to prevent or
      attenuate the progression of GDM to T2DM in these mothers. The knowledge gained
      will be used to introduce feasible, scientifically sound, and culturally
      acceptable postpartum dietary recommendations for GDM mothers.

PMID- 30225271
TI  - miR-125a Suppresses TrxR1 Expression and Is Involved in H2O2-Induced Oxidative
      Stress in Endothelial Cells.
AB  - Thioredoxin reductase (TrxR), an antioxidant enzyme dependent on nicotinamide
      adenine dinucleotide phosphate, plays a vital role in defense against oxidative
      stress. However, the role of microRNAs targeting TrxR under oxidative stress has
      not yet been determined. In this study, we tested the involvement of miRNA
      mediated posttranscriptional regulation in H2O2-induced TrxR1 expression in
      endothelial cells. Dual luciferase assay combined with expression analysis
      confirmed that miR-125a suppressed TrxR1 expression by targeting its 3'-UTR.
      Furthermore, H2O2 induced TrxR1 expression partly through downregulation of miR
      125a. These findings indicate that miRNA-mediated posttranscriptional mechanism
      is involved in H2O2-induced TrxR1 expression in endothelial cells, suggesting an
      important role of miRNAs in the response to oxidative stress.

PMID- 30225272
TI  - A Magnetic Resonance Imaging-Based Staging System for Osteochondritis Dissecans
      of the Elbow: A Validation Study Against the International Cartilage Repair
      Society Classification.
AB  - Background: Evaluations of the stability of osteochondritis dissecans (OCD)
      lesions of the elbow using magnetic resonance imaging (MRI) have resulted in
      reports with variable accuracy. Therefore, the International Cartilage Repair
      Society (ICRS) classification remains the gold standard to determine OCD lesion
      stability. Because OCD commonly occurs in pediatric patients, a noninvasive
      method comparable with the ICRS classification is desired. Hypothesis/Purpose:
      Based on the previous literature, the capitellum of unstable OCD lesions has an
      irregular outline on MRI because of displacement or dislocation of the lesion via
      synovial fluid inflow. Therefore, we defined a 4-stage classification, similar to
      the ICRS classification, which focused on the outline of the capitellum and
      articular cartilage status on MRI without subchondral bone information. The
      purpose of this study was to validate this MRI-based staging system against the
      ICRS classification and to verify its accuracy in diagnosing unstable OCD lesions
      of the elbow. Study Design: Cohort study (diagnosis); Level of evidence, 2.
      Methods: A total of 81 patients with OCD of the elbow who were surgically treated
      were evaluated. The MRI-based stages were as follows: stage 1, normal-shaped
      capitellum and articular cartilage without signal intensity change; stage 2,
      normal-shaped capitellum and articular cartilage with signal intensity change;
      stage 3, irregular-shaped capitellum and discontinuity of the articular
      cartilage; and stage 4, dislocated lesion with an articular cartilage defect.
      Agreement between the MRI and ICRS classifications was evaluated, and the
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) for lesion instability were determined. The intraclass
      correlation coefficient (ICC) for intrarater and interrater reliability of the
      MRI-based staging system was calculated. Results: Agreement between the MRI-based
      staging system and the ICRS classification was 88.9%, with a sensitivity of
      98.4%, specificity of 84.2%, PPV of 95.3%, and NPV of 94.1% for diagnosing an
      unstable lesion. The ICC was high for both intrarater (0.925) and interrater
      (0.915-0.939) reliability. Conclusion: The MRI-based staging system corresponded
      well with the ICRS classification, providing an accurate preoperative assessment
      of OCD lesions of the elbow, even with minimal subchondral bone information.

PMID- 30225273
TI  - Association of Trauma Alert Response Charges With Volume and Hospital Ownership
      Type in Florida.
AB  - Objective: The purpose was to analyze the association of trauma volume and
      hospital trauma center (TC) ownership type with trauma alert (TA) response
      charges, which are billed for activation of the trauma team to the emergency
      department (ED). Methods: All Florida ED and inpatients who were billed a TA
      charge from 2012 to 2014 were included (62 974 observations). Multiple linear
      regression, controlling for patient and hospital factors, was used to identify
      associations between TA charges and trauma volume and hospital ownership type.
      Severity elasticity of trauma response charges was calculated by ownership type.
      Results: Trauma volume had a significant, inverse relationship with TA charges.
      For-profit (FP) hospitals had significantly higher TA charges and government
      owned hospitals had significantly lower TA charges relative to private not-for
      profits. For-profit trauma response charges were inelastic to severity, that is,
      charges did not change with changes in severity. Conclusion: Higher TA charges
      were associated with lower patient volumes, as well as at FP TCs. Further, only
      FP TCs used alert charges that were not associated with injury severity. Adding
      new TCs that reduce volume at existing TCs is expected to increase TA charges,
      especially if they are FP TCs.

PMID- 30225270
TI  - New Insights in the Pathogenesis of HPV Infection and the Associated Carcinogenic
      Processes: The Role of Chronic Inflammation and Oxidative Stress.
AB  - Human papillomavirus (HPV) is a small double-stranded DNA virus with tropism for
      epithelial cells. To this date, over 150 genotypes are known and are classified
      into two major groups, low-risk and high-risk strains, depending on the ability
      of the virus to induce malignant transformation. The host's immunity plays a
      central role in the course of the infection; therefore, it may not be clinically
      manifest or may produce various benign or malignant lesions. The pathogenic
      mechanisms are complex and incompletely elucidated. Recent research suggests the
      role of chronic inflammation and oxidative stress (OS) in the pathogenesis of HPV
      infection and the associated carcinogenic processes. Chronic inflammation induces
      OS, which in turn promotes the perpetuation of the inflammatory process resulting
      in the release of numerous molecules which cause cell damage. Reactive oxygen
      species exert a harmful effect on proteins, lipids, and nucleic acids. Viral
      oncogenes E5, E6, and E7 are involved in the development of chronic inflammation
      through various mechanisms. In addition, HPV may interfere with redox homeostasis
      of host cells, inducing OS which may be involved in the persistence of the
      infection and play a certain role in viral integration and promotion of
      carcinogenesis. Knowledge regarding the interplay between chronic inflammation
      and OS in the pathogenesis of HPV infection and HPV-induced carcinogenesis has
      important consequences on the development of new therapeutic strategies.

PMID- 30225274
TI  - Feasibility of aortic valve planimetry at 7 T ultrahigh field MRI: Comparison to
      aortic valve MRI at 3 T and 1.5 T.
AB  - Introduction: This study examined the feasibility of aortic valve planimetry at 7
      T ultrahigh field MRI in intraindividual comparison to 3 T and 1.5 T MRI.
      Material and methods: Aortic valves of eleven healthy volunteers (mean age, 26.4
      years) were examined on a 7 T, 3 T, and 1.5 T MR system using FLASH and TrueFISP
      sequences. Two experienced radiologists evaluated overall image quality, the
      presence of artefacts, tissue contrast ratios, identifiability, and image details
      of the aortic valve opening area (AVOA). Furthermore, AVOA was quantified twice
      by reader 1 and once by reader 2. Correlation analysis between artefact severity
      and employed magnetic field strength was performed by modified Fisher's exact
      test. Paired t-test was used to analyse for AVOA differences, and Bland-Altman
      plots were used to analyse AVOA intra-rater and inter-rater variability. Results:
      Aortic valve imaging at 7 T, 3 T, and 1.5 T with using FLASH was less hampered by
      artefacts than TrueFISP imaging at 3 T and 1.5 T. Tissue contrast and image
      details were rated best at 7 T. AVOA was measured slightly smaller at 7 T
      compared to 3 T (TrueFISP, p-value = 0.057; FLASH, p-value = 0.016) and 1.5 T
      (TrueFISP, p-value = 0.029; FLASH, p-value = 0.018). Intra-rater and inter-rater
      variability of AVOA tended to be slightly smaller at 7 T than at 3 T and 1.5 T.
      Conclusion: Aortic valve planimetry at 7 T ultrahigh field MRI is technically
      feasible and in healthy volunteers offers an improved tissue contrast and a
      slightly better reproducibility than MR planimetry at 1.5 T and 3 T.

PMID- 30225275
TI  - Data of de novo assembly of the leaf transcriptome in Aegle marmelos.
AB  - Aegle marmelos (Indian Bael) is an important plant from the religious and
      medicinal point of view. Many medicinal compounds are identified from its leaves
      that rendered its use in traditional as well as modern medical system. Still, it
      is quite overlooked from the transcriptome viewpoint. This article provides
      information about the transcriptomic data which is the first ever report about
      this plant. The data is accessible via NCBI BioProject (id PRJNA433585).

PMID- 30225276
TI  - Au courant computation of the PDB to audit diffraction anisotropy of soluble and
      membrane proteins.
AB  - This data article makes available the informed computation of the whole Protein
      Data Bank (PDB) to investigate diffraction anisotropy on a large scale and to
      perform statistics. This data has been investigated in detail in "X-ray
      diffraction reveals the intrinsic difference in the physical properties of
      membrane and soluble proteins" [1]. Diffraction anisotropy is traditionally
      associated with absence of contacts in-between macromolecules within the crystals
      in a given direction of space. There are however many case that do not follow
      this empirical rule. To investigate and sort out this discrepancy, we computed
      diffraction anisotropy for every entry of the PDB, and put them in context of
      relevant metrics to compare X-ray diffraction in reciprocal space to the crystal
      packing in real space. These metrics were either extracted from PDB files when
      available (resolution, space groups, cell parameters, solvent content), or
      calculated using standard procedures (anisotropy, crystal contacts, presence of
      ligands). More specifically, we separated entries to compare soluble vs membrane
      proteins, and further separated the later in subcategories according to their
      insertion in the membrane, function, or type of crystallization (Type I vs Type
      II crystal packing). This informed database is being made available to
      investigators in the raw and curated formats that can be re-used for further
      downstream studies. This dataset is useful to test ideas and to ascertain
      hypothesis based on statistical analysis.

PMID- 30225277
TI  - Dataset on community structure of macro invertebrate fauna in Ubogo river, Udu
      LGA, Delta State, Nigeria.
AB  - The datasets contained in this article are based on a baseline study on the
      selected physicochemical parameters and macro-benthic invertebrates' community of
      Egini, and Ubogo Rivers in Delta State for a period of six months: February -
      July, 2010, within in six stations shared equally among the two rivers using the
      three communities they flow through as guide and water samples collected on
      monthly basis from these stations. The objectives include determination of the
      spatial variations and background concentrations of the selected physicochemical
      parameters, species composition and abundance of the macro-benthic invertebrates.
      Sixteen physicochemical parameters were analyzed in the water. Air and water
      temperature and current velocity were determined in-situ; the rest
      physicochemical parameters were determined adopting standard methods. Dusting
      method was adopted in sampling the macro-benthic invertebrates.

PMID- 30225278
TI  - Data regarding talent management practices and innovation performance of academic
      staff in a technology-driven private university.
AB  - The article presented an integrated data on talent management practices and
      innovation performance of academic staff in a technology-driven private
      university in Nigeria. The study adopted a quantitative approach with a survey
      research design to establish the major determinants of talent management
      practices. The population of this study included academic staff and the use of
      questionnaire was adopted to elicit from the study population. Data was analysed
      with the use of structural equation modelling and the field data set is made
      widely accessible to enable critical or a more comprehensive investigation. The
      findings identified talent development and retention strategies as predictors for
      facilitating innovation performance in the sample University. It was recommended
      that management of the sampled university will consistently need to adopt
      reliable range of strategies to attract and retain people for excellence
      performance.

PMID- 30225279
TI  - A collection of the etiological theories, characteristics, and
      observations/phenomena of peptic ulcers in existing data.
AB  - In this article, we compiled 13 etiological theories, 15 characteristics, and 81
      observations/phenomena of peptic ulcers, reported in reproducible, peer-reviewed
      studies from the literature, to reflect the historical evolution of studies on
      peptic ulcers and to provide a multidisciplinary view of this disease. This data
      was collected during the systematic review of topics on peptic ulcers including
      genetics, etiology, epidemiology, psychology, anatomy, neurology, bacteriology,
      pathology, and clinical statistics. The data curated herein was extracted via
      application of recently published basic theories and methodologies.

PMID- 30225280
TI  - Data on modeling of nexus between entrepreneurs' commitment and business
      performance in a developing country.
AB  - This article presents data that examined the modeling of nexus between
      entrepreneurs' commitment and business performance in a developing country. 315
      copies of questionnaire were retrieved from 400 copies that were administered to
      Nigerian Association of Small Scale Industrialists (NASSI) Southwest chapters
      which comprised of six states. In addition to descriptive analysis of part of the
      data, correlation and regression analysis were used to present the data through
      structural equation model (SEM). The SEM path analysis shows the estimates of the
      interconnectedness of the major constructs in the data.

PMID- 30225281
TI  - Identification of potential biomarkers of head and neck squamous cell carcinoma
      using iTRAQ based quantitative proteomic approach.
AB  - Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers
      in India. Despite improvements in treatment strategy, the survival rates of HNSCC
      patients remain poor. Thus, it is necessary to identify biomarkers that can be
      used for early detection of disease. In this study, we employed iTRAQ-based
      quantitative mass spectrometry analysis to identify dysregulated proteins from a
      panel of head and neck squamous cell carcinoma (HNSCC) cell lines. We identified
      2468 proteins, of which 496 proteins were found to be dysregulated in at least
      two out of three HNSCC cell lines compared to immortalized normal oral
      keratinocytes. We detected increased expression of replication protein A1 (RPA1)
      and heat shock protein family H (Hsp110) member 1 (HSPH1), in HNSCC cell lines
      compared to control. The differentially expressed proteins were further validated
      using parallel reaction monitoring (PRM) and western blot analysis in HNSCC cell
      lines. Immunohistochemistry-based validation using HNSCC tissue microarrays
      revealed overexpression of RPA1 and HSPH1 in 15.7% and 32.2% of the tested cases,
      respectively. Our study illustrates quantitative proteomics as a robust approach
      for identification of potential HNSCC biomarkers. The proteomic data has been
      submitted to ProteomeXchange Consortium
      (http://www.proteomecentral.proteomexchange.org) via the PRIDE public data
      repository accessible using the data identifier - PXD009241.

PMID- 30225282
TI  - Zoning of air quality index (PM10 and PM2.5) by Arc-GIS for Khorramabad city,
      Iran.
AB  - Nowadays in many countries, air pollution is one of the major issues affecting
      human health. Among the various air pollutants particulate matters are mainly
      present in ambient air pollution. The purpose of this study was to measure the
      concentration of particulate matter (PM) (namely PM2.5 and PM10) and to conduct
      zoning via GIS software in Khorramabad city (Summer - 2017). According to the
      findings, the average concentrations of PM2.5 in July, August and September were
      100.1, 116.3, and 199.8 MUg/m3, respectively. Furthermore, the average
      concentrations of PM10 in July, August and September were 199.8, 215.7, and 190.8
      MUg/m3, respectively. The findings of this study also indicated that due to
      continuous dust storms,particularly in recent years, the air pollution status in
      Khorramabad was not suitable that can adversely affect public health.

PMID- 30225283
TI  - Data on subjective recollection effects reflected in large-scale functional
      connectivity patterns in postpartum women.
AB  - Functional neuroimaging data was collected while postpartum women and age-matched
      control women performed the Remember/Know judgment task in the functional
      magnetic resonance imaging scanner. This data provides information about
      functional connectivity patterns across the subjective recollection networks that
      were informative in differentiating the postpartum women from control women.
      Classification performances based on machine learning algorithms and descriptions
      of functional connectivity patterns that derived the peak classification accuracy
      are reported in this article. All other results from our study have been reported
      in Nah et al. (2018) [1].

PMID- 30225284
TI  - Fusarium graminearum1H NMR metabolomics.
AB  - Raw 1H NMR spectra of Fusarium graminearum hyphae can be found at the website of
      the pesticide metabolomics group (PMG) of the Agricultural University of Athens
      at the address: http://www.aua.gr/pesticide
      metabolomicsgroup/Resources/Fusarium_graminearum_NMR_spectra.html, accession
      number PMG-01-17. The data set support the research article "Implication of
      Fusarium graminearum Primary Metabolism in its Resistance to Benzimidazole
      Fungicides as revealed by 1H NMR Metabolomics" [1].

PMID- 30225285
TI  - Data on empirical investigation of direct and indirect effect of personality
      traits on entrepreneurs' commitment of SMEs.
AB  - This data article presented the effect of the Big Five Personality traits on
      entrepreneurs' commitment. 400 copies of questionnaire were administered to
      practicing entrepreneurs whom were members of a business guild in their annual
      end of year meeting and award day. 369 copies were duly filled and returned for
      use. Using statistic package for social science (SPSS 20) and Amos 22,
      correlation and regression analysis were used to find out the relationship
      between the two constructs and the strength of the relationship respectively. The
      Amos path diagram revealed the standardized estimates of the regression
      coefficient.

PMID- 30225286
TI  - UMONS-TAICHI: A multimodal motion capture dataset of expertise in Taijiquan
      gestures.
AB  - In this article, we present a large 3D motion capture dataset of Taijiquan
      martial art gestures (n = 2200 samples) that includes 13 classes (relative to
      Taijiquan techniques) executed by 12 participants of various skill levels.
      Participants levels were ranked by three experts on a scale of [0-10]. The
      dataset was captured using two motion capture systems simultaneously: 1)
      Qualisys, a sophisticated optical motion capture system of 11 cameras that tracks
      68 retroreflective markers at 179 Hz, and 2) Microsoft Kinect V2, a low-cost
      markerless time-of-flight depth sensor that tracks 25 locations of a person's
      skeleton at 30 Hz. Data from both systems were synchronized manually. Qualisys
      data were manually corrected, and then processed to complete any missing data.
      Data were also manually annotated for segmentation. Both segmented and
      unsegmented data are provided in this dataset. This article details the recording
      protocol as well as the processing and annotation procedures. The data were
      initially recorded for gesture recognition and skill evaluation, but they are
      also suited for research on synthesis, segmentation, multi-sensor data comparison
      and fusion, sports science or more general research on human science or motion
      capture. A preliminary analysis has been conducted by Tits et al. (2017) [1] on a
      part of the dataset to extract morphology-independent motion features for skill
      evaluation. Results of this analysis are presented in their communication:
      "Morphology Independent Feature Engineering in Motion Capture Database for
      Gesture Evaluation" (10.1145/3077981.3078037) [1]. Data are available for
      research purpose (license CC BY-NC-SA 4.0), at https://github.com/numediart/UMONS
      TAICHI.

PMID- 30225287
TI  - Data on assessment of physical, chemical and biological characteristics of
      effluent from wastewater treatment in Torbat Heydarieh, Iran.
AB  - Data on the chemical, physical and biological of effluent from wastewater
      treatment are provided in table format in the current article. Samples were taken
      in Peak Flows at effluent Treatment Plants. Sampling and tests were conducted
      according to the standards methods. The collected data were analyzed by SPSS
      software and excel program. Nickel metal showed higher amounts than the standards
      required for irrigation agricultural land. Data could be useful from
      environmental and agricultural sciences to those concerned about heavy metals,
      Alkalinity, EC, COD, BOD5 and Microbial concentrations threats.

PMID- 30225288
TI  - Data article on institutional framework and business survivals of informal
      entrepreneurs in electronics market, Southwest, Nigeria.
AB  - The article presented data on how institutional framework has provided
      opportunities for the survival of informal entrepreneurs. In other words, data
      were gathered based on how the informal entrepreneurs in the electronics market
      were able to manipulate or avoid law enforcement officials thereby leading to
      sustainable business performance. Emphasis was laid on four southwestern states
      in Nigeria to determine the survivals of informal business. Data were gathered
      based on descriptive survey research design. The population of this study
      included all informal entrepreneurs in some selected electronics markets. Mean
      score and standard deviation were used as statistical tools for data
      presentation. The field data set is made widely accessible to enable critical or
      a more comprehensive investigation.

PMID- 30225289
TI  - Estimated hemodynamic response function parameters obtained from resting state
      BOLD fMRI signals in subjects with autism spectrum disorder and matched healthy
      subjects.
AB  - In Functional magnetic resonance imaging (fMRI), the blood oxygen level dependent
      (BOLD) signal is modeled as a convolution of the hemodynamic response function
      (HRF) and the unmeasured latent neural signal. Although most cortical and
      subcortical brain regions share the canonical shape of the HRF, the temporal
      structure of HRFs are variable across brain regions and subjects. This
      variability is induced by both neural and non-neural factors. The variability
      between subjects can be examined by three parameters that characterize the HRF:
      response height (RH), time-to-peak (TTP) and full-width at half-max (FWHM). This
      data provides three HRF parameters at every voxel, obtained from Autism Spectrum
      Disorder (ASD) patients (N = 531), and matched healthy controls (N = 571). Since
      ongoing studies suggest that non-standard populations have important differences
      in their HRFs when compared with healthy control, this data set is valuable in
      studying variability of HRF in ASD group and inferring the underlying pathology
      that also affects the HRF. It also has implications for fMRI analyses like
      resting-sate connectivity analysis.

PMID- 30225290
TI  - Description of long-term monitoring of farmland biodiversity in a LTSER.
AB  - Understanding the response of biodiversity to management, land use and climate
      change is a major challenge in farmland to halt the decline of biodiversity.
      Farmlands shelter a wide variety of taxa, which vary in their life cycle and
      habitat niches. Consequently, monitoring biodiversity from sessile annual plants
      to migratory birds requires dedicated protocols. In this article, we describe the
      protocols applied in a long-term research platform, the LTSER Zone Atelier
      "Plaine & Val de Sevre" (for a full description see Bretagnolle et al. (2018)
      [1]). We present the data in the form of the description of monitoring protocols,
      which has evolved through time for arable weeds, grassland plants, ground
      beetles, spiders, grasshoppers, wild bees, hoverflies, butterflies, small
      mammals, and farmland birds (passerines, owls and various flagship species).

PMID- 30225291
TI  - Adsorption of organic pollutants from real refinery wastewater on prepared cross
      linked starch by epichlorohydrin.
AB  - The presented data shows how cornstarch can be modified to a material that can
      effectively remove organics pollutants from a real wastewater. A low-cost
      adsorbent obtained from cornstarch by the crosslinking with epichlorohydrin. The
      prepared crossed linked starch (CLS) adsorbent characterized by X-ray
      diffraction, zeta potential, Fourier-transform infrared spectroscopy, atomic
      force microscopy, scanning electron microscopy, and Brunauer-Emmett-Teller
      surface area. The effects of initial chemical oxygen demand of the real
      wastewater, temperature and time of the adsorption of the organics on the
      prepared CLS were analyzed. The removal of the highest organics concentration was
      89.85%. Langmuir and Freundlich isotherm models have been applied to investigate
      the adsorption equilibrium. The maximum adsorption capacity of the organics
      pollutants on the prepared CLS was 256.41 mg/g. Thermodynamic parameters show
      that the adsorption process of organics on CLS is more favorable at low
      temperature.

PMID- 30225292
TI  - Data set of the toxic effects of divaricatic acid depside on Biomphalaria
      glabrata and Schistosoma mansoni cercariae.
AB  - In this study, the molluscicidal and antiparasitic activities of divaricatic acid
      was evaluated, targeting the mollusc Biomphalaria glabrata and cercariae of the
      helminth Schistosoma mansoni. Divaricatic acid showed high toxicity against both
      adult snails (5.5 MUg/mL) and embryos (20 MUg/mL after 6 h of exposure). Similar
      activity was observed in S. mansoni cercariae after only a short exposure time.
      The divaricatic acid proved to be a promising substance for the control of the
      snail B. glabrata, an intermediate host of schistosomiasis, as well as the
      cercariae of the pathogen.

PMID- 30225293
TI  - Life cycle inventories of waste management processes.
AB  - To allow for an up-to-date and geographically specific life cycle assessment,
      updated and regionally specific life cycle inventories are crucial. This data
      article present up-to-date life cycle inventories of several collection, sorting
      and recycling processes of municipal solid waste fractions for life cycle
      assessments of waste management systems. In total, 190 life cycle inventories for
      processes within municipal solid waste management were either newly developed or
      adapted from existing datasets. The data for 51 recycling processes has been
      collected to update existing processes or create new process models. Two modules
      for biogenic processes were taken from literature and 10 processes were modeled
      based on the existing ecoinvent processes with minor adjustments [1]. The
      substitution of 36 materials from recycling processes was modeled. In addition,
      the thermal treatment of 12 waste fractions was modeled within 84 life cycle
      inventories compromising the thermal waste treatment and the recovery and
      recycling of recovered fractions from fly and bottom ash. The assumptions and the
      modelling of the waste treatment processes are described. All life cycle
      inventory datasets which were newly created, updated or modified compared to the
      original dataset are described and provided as Excel table. The data are
      associated with the research article "Modular Life Cycle Assessment of Municipal
      Solid Waste Management" [2].

PMID- 30225294
TI  - Unicode-8 based linguistics data set of annotated Sindhi text.
AB  - Sindhi Unicode-8 based linguistics data set is multi-class and multi-featured
      data set. It is developed to solve the natural languages processing (NLP) and
      linguistics problems of Sindhi language. The data set presents information on
      grammatical and morphological structure of Sindhi language text as well as
      sentiment polarity of Sindhi lexicons. Therefore, data set may be used for
      information retrieving, machine translation, lexicon analysis, language modeling
      analysis, grammatical and morphological analysis, Semantic and sentiment
      analysis.

PMID- 30225295
TI  - Data on anti-corrosion characteristics of eco-friendly inhibitive extract on the
      hot corrosion degradation trend of A6063 aluminum alloy in 1.0 M HCl solution.
AB  - The study of Lasienthera africanum as corrosion inhibitor for A6063 grade
      aluminum alloy in 1.0 M HCl acid solution using weight loss method of corrosion
      study was investigated at 30  degrees C and 40  degrees C to check its
      degradation trend at high varying temperature application. The results revealed
      that L. africanum in 1.0 M acidic environment decreased the corrosion rate at
      various concentrations considered. Inhibitor efficiency (IE) as high as 98.7 and
      94.9% both at 30  degrees C and 40  degrees C respectively, was observed.

PMID- 30225296
TI  - Data on chemical composition of soil and water in the semiarid wetland of Las
      Tablas de Damiel National Park (Spain) during a drought period.
AB  - Las Tablas de Daimiel National Park (TDNP) is a Ramsar Mediterranean wetland area
      designated as Biosphere Reserve by Unesco. The whole system dried out during a
      long drought period in the past decade (2006-2009) and a smouldering peat fire
      took place in 2009. The physical and chemical properties of sediments were
      significantly disturbed by the fire. To date, the ecological system has not fully
      recovered from the impact. We present a raw data collection of the chemical
      composition of soil, groundwater and surface water sampled over four consecutive
      years in 2006-2010. The data include major and minor anions and cations,
      nutrients and heavy metals. Sampling points were located inside and outside TDNP
      both upstream as well as downstream. The information provided can be used to
      analyse the medium and long term impact of drought and smouldering fire to the
      TDNP environment. It is also a baseline for hydro-ecological modelling of the
      impact of climate change in arid and semiarid wetlands to develop adaptive
      management strategies.

PMID- 30225297
TI  - Data on trend changes of drinking groundwater resources quality in Sabzevar city
      (A case study).
AB  - The data of this study was conducted to evaluate the groundwater quality trend
      changes in Sabzevar (Iran, Khorasan Razavi) during one decade (2006-2016). The
      Mean +/- SD of electrical conductivity (as umhos/cm), total hardness (as calcium
      carbonate, mg/l) and total dissolved solid in the first and end year of the study
      were 605.45 +/- 194.69 and 695.22 +/- 288.52, 198.77 +/- 56.83 and 214.45 +/-
      84.73, 350.25 +/- 106.81 and 486.44 +/- 183.52 respectively. At the end of the
      results were compared with WHO (World Health Organization) guideline and Iranian
      drinking water standard (No. 1053). The results show that all of the evaluated
      parameters were less than the WHO guideline and the Iranian drinking water
      standard, only the TH (Total Hardness) was higher than the standard range. On the
      basis of Pearson correlation coefficient, the ascending trend of some parameters
      concentration with time was significant at the level of 95% of confidence limits
      (alpha <= 0.05).

PMID- 30225298
TI  - Whole-genome sequence data and analysis of a Staphylococcus aureus strain
      SJTUF_J27 isolated from seaweed.
AB  - The complete genome sequence data of S. aureus SJTUF_J27 isolated from seaweed in
      China is reported here. The size of the genome is 2.8 Mbp with 32.9% G + C
      content, consisting of 2614 coding sequences and 77 RNAs. A number of virulence
      factors, including antimicrobial resistance genes (fluoroquinolone, beta-lactams,
      fosfomycin, mupirocin, trimethoprim, and aminocoumarin) and the egc enterotoxin
      cluster, were found in the genome. In addition, the genes encoding metal-binding
      proteins and associated heavy metal resistance were identified. Phylogenetic data
      analysis, based upon genome-wide single nucleotide polymorphisms (SNPs), and
      comparative genomic evaluation with BLAST Ring Image Generator (BRIG) were
      performed for SJTUF_J27 and four S. aureus strains isolated from food. The
      completed genome data was deposited in NCBI's GenBank under the accession number
      CP019117, https://www.ncbi.nlm.nih.gov/nuccore/CP019117.

PMID- 30225299
TI  - Hydrocortisone 21-hemisuccinate did not prevent exogenous GAPDH-induced apoptosis
      in human neuroblastoma cells.
AB  - These data are related to our paper "GAPDH-targeted therapy - a new approach for
      secondary damage after traumatic brain injury on rats" (Lazarev et al., In
      press), in which we explore the role of exogenous GAPDH in traumatic brain injury
      induced neuron death, and the therapeutic application of small molecules that
      bind to the enzyme. The current article demonstrates the induction of apoptosis
      by exogenous GAPDH and the effectiveness of the hydrocortisone derivative for
      suppressing the pathogenic action of the enzyme.

PMID- 30225300
TI  - Data on the alizarin red S adsorption from aqueous solutions on PAC, treated PAC,
      and PAC/gamma~Fe2O3.
AB  - Three types of adsorbents of powdered activated carbon (PAC), treated PAC, and
      PAC/gamma ~ Fe2O3 nanocomposite were used. The adsorption experiments were
      performed in batch conditions. pHZPC of PAC/gamma ~ Fe2O3 was 6.7. As a result,
      at lower than pHZPC, acidic pH, the adsorption of alizarin red S on PAC/gamma ~
      Fe2O3 was favourable. The maximum of alizarin red S adsorption of PAC, treated
      PAC, and PAC/gamma ~ Fe2O3 was 24.5 mg/g, 57.8 mg/g, and 112.56 mg/g,
      respectively. The models of Langmuir and pseudo-first-order were a fit model to
      describe the adsorption isotherm and the Kinetic, respectively. The PAC/gamma ~
      Fe2O3 is a promising class of the adsorbents in the adsorption of various dyes
      from textile effluents.

PMID- 30225301
TI  - Proteomics dataset containing proteins that obscure identification of TOPLESS
      interactors in Arabidopsis.
AB  - Here we report proteins identified after conducting Tandem Affinity Purification
      (TAP) of the TOPLESS (TPL) corepressor from Arabidopsis. We generated transgenic
      plants harboring TPL fused to the GS-TAG, "Boosting tandem affinity purification
      of plant protein complexes" (Van Leene et al., 2008) [1]. Four independent
      biological replicates of a selected TPL-GS-TAG line were grown simultaneously,
      crosslinked with formaldehyde, and proteins were isolated from whole plant tissue
      via TAP. Purified proteins were treated with trypsin, and the peptides were
      analyzed via mass spectrometry. Datasets are hosted in the MassIVE public
      repository (reference number: MSV000082477,
      https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=f16255fb7080426a9fe1926b4d3d
      862). The data in this article has not been published elsewhere and is original
      to this work.

PMID- 30225302
TI  - Dataset on phytochemical screening, FTIR and GC-MS characterisation of
      Azadirachta indica and Cymbopogon citratus as reducing and stabilising agents for
      nanoparticles synthesis.
AB  - The dataset for this article contains phytochemical and FTIR data for three
      different extracts from two indigenous medicinal plants obtained from Ogun State,
      Southwest Nigeria and the GC-MS characterisation data for their ethanolic
      extracts. To obtain this data, the leaves of Azadirachta indica and Cymbopogon
      citratus were collected from the premises of Covenant University, Nigeria. The
      plants were dried, pulverized and extracted with ethanol, distilled water and
      ethanol:water (50:50), before phytochemical screening (qualitative and
      quantitative), FTIR and GC-MS analyses were carried out. The dataset provides
      insight into the presence of bioactive phyto-constituents such as polyphenols and
      tannins as potential precursors for green-based nanoparticle synthesis.

PMID- 30225303
TI  - Data on the fluorescence quenching analysis of BSA induced by pyrene and/or 1
      hydroxypyrene in binary and ternary systems.
AB  - This article present data related to the publication entitled "Interactions of
      pyrene and/or 1-hydroxypyrene with bovine serum albumin based on EEM-PARAFAC
      combined with molecular docking" (Zhang et al., 2018) [1]. The excitation
      emission matrix (EEM) fluorescence spectral parameters of pyrene, 1
      hydroxypyrene, bovine serum albumin (BSA), and their mixtures were presented in
      this article. Combined EEM - parallel factor analysis with fluorescence quenching
      analysis, some data related to the binding affinity of pyrene and/or 1
      hydroxypyrene with BSA in the binary and ternary systems were obtained.

PMID- 30225304
TI  - Data on the synthesis and characterization of two novel polydentate ligands
      possessing unsymmetrical NH-urea fragment.
AB  - The data represent the synthesis and structural characterization of two novel
      polydentate ligands possessing unsymmetrical NH-urea fragment: an open-chain
      substituted aromatic compound with unsymmetrical urea and secondary amine units
      (S1) and fused aryloxazinone with unsymmetrical urea fragment (S2). The data
      include the analyzed NMR spectra, turbo-spray mass spectra, melting points and Rf
      values. 1D and 2D NMR spectra are given in the article. The efficiency of the
      ligands as synergists in the isolation and separation of lantanoid ions is
      reported in rerence. [1].

PMID- 30225306
TI  - Dataset on investigating the effect of sunflower based biodiesel on the rheology
      of Nigeria waxy crude oil.
AB  - This paper presents information about the data obtained from the experimental
      research showing the effect of sunflower based biodiesel on rheological
      properties of Nigeria waxy crude oil. The information reported in the dataset
      depicts 0.1-0.7% dosing concentration of sunflower based biodiesel might be
      required for viscosity reduction of Nigeria waxy crude oil at operational
      temperatures ranging from 10  degrees C (at low temperature region) to 60 
      degrees C (at mid temperature region). It has also demonstrated that biodiesel
      derived from sunflower is technically viable to decrease the viscosity of Nigeria
      waxy crude oil appreciably, hence revealing its potential capacity to enhancing
      flow of the oil in pipeline and wellbore system.

PMID- 30225305
TI  - Contemporaneous data on the prevalence of Human Respiratory Syncytial Virus
      infection in people with acute respiratory tract infections in Africa (2000
      2017).
AB  - Availability of accurate data on the burden of the Human Respiratory Syncytial
      Virus (HRSV) can help to implement better strategies to curb this burden in
      Africa continent among people with acute respiratory tract infections (ARTI). We
      summarize here available contemporaneous data published from January 1, 2000 to
      August 31, 2017 on the prevalence of HSRV infection among people with ARTI in the
      continent.

PMID- 30225307
TI  - Data on soil physicochemical properties and chemical composition of rainfall and
      of throughfall and stemflow generated by Turkey oak trees (Quercus cerris L.) in
      acid and sub-alkaline soils.
AB  - We report data on the physicochemical properties of soils collected in two
      adjacent areas, one acid and one sub-alkaline, both developed on sequential beds
      of Plio-pleistocene marine sediments, and on the chemical composition of
      ecological solutions (rainfall, throughfall and stemflow) separately collected in
      the two areas. Throughfall and stemflow were generated by Turkey oak trees
      (Quercus cerris L.), which was the dominant tree species in both study areas.
      These data are related to the original article "Soil affects throughfall and
      stemflow under Turkey oak (Quercus cerris L.)" (Corti et al., 2019) [1].

PMID- 30225308
TI  - Kinetic and modeling data on phenol removal by Iron-modified Scoria Powder (FSP)
      from aqueous solutions.
AB  - Phenol present in industrial effluents is a toxicant matter which causes
      pollution of environments aqueous. In this work, scoria was modified by iron in
      order to increasing of adsorbent efficiency and effective removing of phenol.
      Effects of independent variables including pH, adsorbents dosage, contact time
      and adsorbate concentration on removing of phenol were studied by response
      surface methodology (RSM) based on the central composite designs (CCD). The
      characterization of raw scoria powder (RSP) and Iron-modified Scoria Powder (FSP)
      was determined via Fourier transform infrared spectroscopy (FTIR), X-ray
      diffraction (XRD), scanning electron microscopy (SEM) and Energy-dispersive X-ray
      spectroscopy (EDS). The obtained data showed modification by iron caused the
      growth of new crystalline of iron oxide on the surface of FSP. Evaluated data by
      RSM indicated the all variables especially pH are effective in removing of phenol
      (P-value < 0.001) and optimum condition was obtained at pH = 5, phenol
      concentration = 50 mg/l, adsorbent dosage = 1 g/l and contact time = 100 min to
      the value of 94.99% with desirability of 0.939. Results revealed that data were
      fitted by Langmuir isotherm (R2 = 0.9938) and pseudo second order kinetic (R2 =
      0.9976). It was found that iron causes increasing the site active of scoria and
      let to significant removal of phenol.

PMID- 30225309
TI  - Factors influencing SMEs CloudERP adoption: A test with generalized linear model
      and artificial neural network.
AB  - This article present data concerning the factors influencing small and medium
      sized enterprises (SMEs) intention to use/adopt CloudERP system in Jordan.
      Generalized Linear Modeling (GLM) and Artificial Neural Network (ANN) modeling
      techniques in R version 1.0.136 were used to analyze data obtained from 394 SMEs.
      Computer self-efficacy, organizational support, perceived usefulness, perceived
      ease of use, facilitating conditions, security and relative advantage have
      significant influence on the intention to use/adoption CloudERP systems. The
      survey data-set is made publicly available to amplify further inquiry.

PMID- 30225310
TI  - Differential expression analysis of transcriptome data of Trypanosoma brucei RBP6
      induction in procyclics leading to infectious metacyclics and bloodstream forms
      in vitro.
AB  - We used an in vitro system based on the inducible expression of the RNA binding
      protein 6 (RBP6) to monitor transcriptome changes during the differentiation of
      Trypanosoma brucei from non-infectious procyclics to infectious metacyclics and
      from metacyclics to bloodstream forms. This data file describes the
      bioinformatics analysis of 20 distinct RNA-Seq samples, with four biological
      replicates each, highlighting differential transcript abundance. Additional
      functional annotation analysis using Gene Ontology is also presented. Complete
      raw data files were deposited at the NCBI Sequence Read Archive - SRA at
      http://www.ncbi.nlm.nih.gov/Traces/sra/sra.cgi with accession numbers: SRP153824,
      SRP153562, and SRP152737.

PMID- 30225311
TI  - Data on the UV filtering and radical scavenging capacity of the bitter masking
      flavanone Eriodictyol.
AB  - A computational analysis of UV filtering and radical scavenging capacity of a
      flavanone, Eriodictyol has been performed under DFT-B3LYP/6-31+ G (d, p).
      Eriodictyol is nontoxic and nonirritant bitter masker used in wine and can be
      used for photo protection due to its potential UV filtering and radical
      scavenging capacity. The compound has an absorbance in the UV-A and UV-B region
      of electromagnetic spectrum, it can be used as a potential UV filter in sunscreen
      lotions and other cosmetic products. Eriodictyol is a potent antioxidant than the
      most commonly studied Quercetin. The most active site in the compound is 3'
      position and is confirmed by NPA, NBO and pKa value analysis. The BDE values
      follow the order 3'<4'<7<5. The major transitions in the UV-visible spectrum of
      Eriodictyol are between HOMO and HOMO-1 with LUMO level and are well explained by
      NBO-NLMO tool in G09.

PMID- 30225312
TI  - Data on perceived excessive workload on faculty members' commitment.
AB  - For this article, the survey data on the effect of perceived excessive workload
      on faculty members' commitment was presented. This data was gathered from an
      academic environment using the full time faculty members of Covenant University.
      The descriptive research design method was employed. The initial sample size used
      for the analysis was 228 faculty members but only 189 copies of questionnaire
      were returned. Statistical package for social sciences (SPSS) was used for the
      coding of the data. The validity and reliability of the research instrument were
      carried out using Cronbach Alpha. Descriptive analysis was used for the
      presentation of the data. This data is made publicly available to assist further
      study in the area of workload and employees commitment.

PMID- 30225313
TI  - Data on the pre-MDA and post MDA interventions for Schistosoma mansoni and
      Schistosoma haematobium in a co-endemic focus in Uganda: 1951-2011.
AB  - The dataset for this article contains Urinary and Intestinal Schistosomiasis from
      Lango region, northern Uganda which is the only known co-endemic region for
      S.mansoni and S.haematobium. Reported in the data, is the retrospective data
      review for historical information before interventions were implemented before
      2003 and after interventions were implemented in 2003 by the national control
      program. In 2007 and 2011, parasitological surveys were conducted in the region
      to validate Schistosomiasis trends following World Health Organization (WHO)
      guidelines for surveys. In addition, malacological surveys were undertaken in
      2007 to assess local transmission potential. The dataset can provide an insight
      into the health implications of Schistosomiasis control in co-endemic focus in
      Uganda, "The epidemiology of schistosomiasis in Lango region Uganda 60 years
      after Schwetz 1951: Can schistosomiasis be eliminated through mass drug
      administration without other supportive control measures?" (Adriko et al., 2018)
      [10].

PMID- 30225314
TI  - Data on organochlorine concentration levels in soil of lowland paddy field,
      Kelantan, Malaysia.
AB  - The main goal of this research work is to measure the concentration levels of
      organochlorine residue in soil. The potential health risk of this pollutant on
      human was also determined. 10 samples were taken from a lowland paddy field
      situated in Kelantan, Malaysia. Physical parameters namely soil pH, organic
      carbon content, water content and particle size were identified to evaluate the
      quality of soil from the agriculture site. Soxhlet extraction and florisil clean
      up process were applied to isolate 10 targeted organochlorine compounds prior to
      the final determination using a gas chromatography-electron capture detector.
      Soil from the lowland has characteristics such as slightly acidic, low organic
      carbon content, high water content and texture dominated by the sandy type.
      Concentration levels of six detected organochlorine pesticides were calculated in
      ug/kg. Hazard quotient value in all samples was less than the acceptable risk
      level HQ <= 1, thus reflecting the status of soil in the subjected area as
      unlikely to pose any adverse health effects.

PMID- 30225315
TI  - Data on the main working conditions with influence on the development of hearing
      loss amongst the occupational population in Spain.
AB  - Obtaining reliable and objective data on certain working conditions is necessary
      to analyse the causes and variables that can influence the development of hearing
      loss amongst the working population. Objective occupational data have been
      collected from a heterogeneous sample of 1418 workers in Spain, see "How activity
      type, time on the job and noise level on the job affect the hearing of the
      working population. Using Bayesian networks to predict the development of
      hipoacusia" (Barrero et al., 2018) [1]. Among the main factors analysed are the
      noise levels to which these workers are exposed, measured at their respective
      workstations, and the assessment of their hearing status, evaluated by
      audiometric medical tests. These factors provide information to predict the
      development of hypoacusia.

PMID- 30225316
TI  - End-member compounds of a 4-sublattice model of multicomponent BCC solid
      solutions.
AB  - The article presents ab initio calculated properties (total energies, lattice
      parameters, and elastic properties) for the complete set of 1540 end-member
      compounds within a 4-sublattice model of Fe-based solid solutions. The compounds
      are symmetry-distinct cases of integral site occupancy for superstructure Y
      (space group #227, type LiMgPdSn) chosen to represent the ordered arrangements of
      solvent atoms (Fe), solute atoms (Fe, Mg, Al, Si, P, S, Mn, Ni, Cu), and
      vacancies (Va) on the sites of a body-centered cubic lattice. The model is
      employed in the research article "Ab-initio based search for late blooming phase
      compositions in iron alloys" (Hosseinzadeh et al., 2018) [1].

PMID- 30225317
TI  - Blue light triggered generation of reactive oxygen species from silica coated
      Gd3Al5O12:Ce3+ nanoparticles loaded with rose Bengal.
AB  - This data article provide results of the studies conducted to develop a
      mesoporous silica coated Gd2.98Ce0.02Al5O12 nanoparticles loaded with a
      photosensitizer dye rose Bengal (RB) system (GAG@mSiO2@RB) capable of producing
      reactive oxygen species (ROS) upon exposure to blue light. The data reported here
      is related with Jain et al. (2018) [1]. It contains histogram of particle size
      distribution, cathodoluminescence (CL), photoluminescence spectra and there
      spectral overlap with the absorption spectra of RB, a graph showing the loading
      percentage of RB at different concentrations. Moreover, the data indicating ROS
      generation evaluated using 1,2-diphenylisobenzofuran (DPBF) assay and the
      viability of MDA-MB-231 cells upon exposure with different concentration of
      GAG@mSiO2 nanoparticles, upon exposure with blue light is also included in the
      data.

PMID- 30225318
TI  - Data related to the sinter structure analysis of titanium structures fabricated
      via binder jetting additive manufacturing.
AB  - The adoption of metal binder jetting additive manufacturing (AM) for functional
      parts relies on a deep understanding between the materials, the design aspects,
      the additive manufacturing process and sintering. This work focuses on the
      relationship between sintering theory and process outcomes. The data included in
      this article provides additional supporting information on the authors' recent
      publication (Wheat et al., 2018 [1]) on the sinter structure analysis of
      commercially pure titanium parts manufactured using powder bed binder jetting
      additive manufacturing. For this work, commercially pure titanium was deployed to
      study the effect of powder size distributions on green and sintered part
      qualities (bulk density, relative density, particle size, pore size, sinter neck
      size). This manuscript includes the overall computed tomography visualization
      methods and results for the green and sintered samples using uni- and bi-modal
      powders. Moreover, the effective particle and pore size for the different batches
      of powder are presented.

PMID- 30225319
TI  - Data on performance prediction for cloud service selection.
AB  - This paper contains data on Performance Prediction for Cloud Service Selection.
      To measure the performance metrics of any system you need to analyze the features
      that affect these performance, these features are called " workload parameters".
      The data described here is collected from the KSA Ministry of Finance that
      contains 28,147 instances from 13 cloud nodes. It was recorded during the period
      from March 1, 2016, to February 20, 2017, in continuous time slots. In this
      article we selected 9 workload parameters: Number of Jobs in a Minute, Number of
      Jobs in 5 min, Number of Jobs in 15 min, Memory Capacity, Disk Capacity,: Number
      of CPU Cores, CPU Speed per Core, Average Receive for Network Bandwidth in Kbps
      and Average Transmit for Network Bandwidth in Kbps. Moreover, we selected 3
      performance metrics: Memory utilization, CPU utilization and response time in
      milliseconds. This data article is related to the research article titled "An
      Automated Performance Prediction Model for Cloud Service Selection from Smart
      Data" (Al-Faifi et al., 2018) [1].

PMID- 30225320
TI  - Qualitative analysis of acid washed black cumin seeds for decolorization of water
      through removal of highly intense dye methylene blue.
AB  - Dyes in water change the colour, taste and odour of water, are highly visible,
      and can be toxic and cancerous for the coloured water consumption human beings.
      Basic dyes particularly, methylene blue, MB has high colour intensity, shows
      intense colour even at low concentration, and are very toxic due to their complex
      structure. Instead of adsorption, removal of MB from water using various
      traditional treatment methods is costly and less effective. The use of
      bioadsorbent provides easy and low cost technique for removal of MB. For
      searching the adequate technique of dye removal, adsorption efficiency and
      mechanism of bioadsorbent can be analyzed. To this, MB removal efficiency of
      seeds of medicinal plant, black cumin seeds were analyzed. The data are supplied
      in the article.

PMID- 30225321
TI  - Dataset on the role of endoglin expression on melanin production in murine
      melanoma and on the influence of melanin on optical imaging.
AB  - The underlying data demonstrates that the expression of endoglin in murine
      melanoma cells influences melanin production in the cells. Also, the data shows
      that melanin production is further increased when the cells are subcutaneously
      implanted in mice models and that the high melanin production prevents detection
      of the cells by fluorescence imaging. The processed data presented herein is
      related to a research article by Tansi et al. (2018) entitled "Endoglin based in
      vivo near-infrared fluorescence imaging of tumor models in mice using activatable
      liposomes".

PMID- 30225322
TI  - Data on the epidemiology, diagnosis, and treatment of patients with pneumothorax.
AB  - This data was acquired using a cross-sectional design in which medical records of
      patients admitted at Arya and Razi Hospitals of Rasht from 2006 to 2015 were
      examined. The patients' demographic data, history of smoking and opium,
      underlying disease, clinical symptoms at admission, the utilized diagnostic
      method, duration of hospitalization, findings of chest CT scan, type of
      pneumothorax, and therapeutic technique were collected through a questionnaire.
      The collected data were encoded and analyzed using SPSS 21.0. Smoking rate was
      measured in the primary and secondary spontaneous pneumothorax groups and
      acquired pneumothorax group. The most frequent underlying disease in the patients
      with secondary spontaneous pneumothorax (SSP) was COPD that was observed in 41
      patients (51.25%). The frequency of bleb was measured in the three groups. Out of
      38 patients (15.01%) with recurrence of pneumothorax, 68.42% had PSP type. Chest
      tube was the most frequently used therapeutic technique, which was utilized
      92.88% out of 235 patients.

PMID- 30225323
TI  - Order type dataset analysis for fiducial markers.
AB  - Order Type (OT) describes a point set avoiding the use of metric information. We
      show that OT is a descriptor which is invariant to Euclidean geometric
      transformations, change of scale and perspective projection. In this paper we
      provide the data related to the application of Order Type with sets of 5, 6, 7,
      and 8 points to build fiducial markers. The OT is represented through a lambda 
      matrix. We provide the set of points which are suitable to solve directly the
      point matching, because these have a unique associated lambda -matrix. We provide
      maximal perturbation data for all set of points, maximal perturbation is the
      radius of the circle, centered in each point in the set, inside which each point
      can be moved without changing its associated OT. Also we provide the scripts to
      validate the use of OT in fiducial markers.

PMID- 30225324
TI  - Main crustal seismic sources in El Salvador.
AB  - We present a map and a data set containing information about intra-plate seismic
      sources in El Salvador. These are the results of the field campaigns and data
      analysis carried out by the research group of Planetary Geodinamics, Active
      Tectonics and Related Risks from Complutense University of Madrid during the last
      12 years. We include two maps, the first map contains 1405 fault traces with
      evidences of Quaternary activity derived form morphometric, paleoseismological
      and geomorphological analysis together with field data mapping carried in El
      Salvador. The second map is a synthesis of the 29 intra-plate seismic sources
      selected from the quaternary faults map. The geometry of these sources was
      simplified and we also include a table where some available data of the proposed
      sources are included, such as their name, orientation, length and slip-rate. For
      further interpretation and discussion of these sources see (Alonso-Henar et al.,
      2018) [1, doi.org/10.1016/j.enggeo.2018.06.015].

PMID- 30225325
TI  - Chemical synthesis of lipophilic methylene blue analogues which increase
      mitochondrial biogenesis and frataxin levels.
AB  - As part of an ongoing program to develop potential therapeutic agents for the
      treatment of the neurodegenerative disease Friedreich's ataxia (FRDA), we have
      prepared a number of lipophilic methylene blue analogues. Some of these compounds
      significantly increase mitochondrial biogenesis and frataxin levels in cultured
      Friedreich's ataxia cells [1]. This data article describes the chemical synthesis
      and full physicochemical characterization of the new analogues.

PMID- 30225326
TI  - Data on the environmental exposure to lead in Iran.
AB  - The data was obtained to present the environmental and occupational exposure to
      lead in Iranian populations based on the published articles. To acquire the data,
      online resources including Google Scholar, Magiran, SID, Iranmedex, PubMed, and
      Science Direct were searched and 104 articles were found out of which 70 that
      focused on the level of lead in blood, urine, milk, and hair of different Iranian
      populations were selected. Since the results of the studies were not homogenous,
      it was not possible to carry out a meta-analysis. The average blood lead level
      (BLL) among workers, ordinary people, patients with specific diseases, addicts,
      and pregnant women, women in labor, infants, and children are presented in this
      article. The average BLL was compared to the standards.

PMID- 30225327
TI  - Performance output data and configurations of stencil compilers experiments run
      through PROVA!
AB  - The data in this article are related to the research article titled "Reproducible
      Stencil Compiler Benchmarks Using PROVA!". Stencil kernels have been implemented
      using a naive OpenMP (OpenMP Architecture Review Board, 2016) [1] parallelization
      and then using the stencil compilers PATUS (Christen et al., 2011) [2] and
      (Bondhugula et al., 2008) PLUTO [3]. Performance experiments have been run on
      different architectures, by using PROVA! (Guerrera et al., 2017) [4], a
      distributed workflow and system management tool to conduct reproducible research
      in computational sciences. Information like version of the compiler, compilation
      flags, configurations, experiment parameters and raw results are fundamental
      contextual information for the reproducibility of an experiment. All this
      information is automatically stored by PROVA! and, for the experiments presented
      in this paper, are available at https://github.com/sguera/FGCS17.

PMID- 30225328
TI  - Effect of layer thickness and annealing temperature on the electrocatalytic
      activity of CNT/Pt counter electrode for triiodide reduction.
AB  - The data presented in this article are related to the research article entitled
      "Balance between the charge transfer resistance and diffusion impedance in a
      CNT/Pt counter electrode for highly efficient liquid-junction photovoltaic
      devices" (Dao and Choi, 2018) [1]. This article presents the effect of annealing
      temperature and thickness of CNT/Pt film on the electrocatalytic activity of
      CNT/Pt counter electrode for triiodide reduction. For this purpose, we firstly
      fabricated CNT/Pt paste with different amount of CNT/Pt. The CNT/Pt film is then
      fabricated by doctor blade method.

PMID- 30225329
TI  - Data on investigating the quantitative and qualitative status of effluent in a
      petrochemical complex in Iran.
AB  - The aim of this data was investigating the quantity and quality of the produced
      effluent by different petrochemical industry units in Iran and comparison of
      effluent with the present standards. In the present data, 5 effluent channel of
      the complex with interval of 12 h (in two shifts) were sampled and 28 physical
      and chemical parameters were analyzed according to the standard methods. These
      parameters are pH, Temperature, DO, Conductivity, Color, TDS, TSS, TP, PO43-,
      Oil, BOD5, COD, Turbidity, TKN, Fe, Ca2+, Mg2+, Cl-, SO42-, Si4+, CO32-, HCO3,
      NO2-, NO3-, NH3, Na, K+, Mn2+. Then, the average of each parameter was obtained
      for each channel, and finally, values of these parameters were compared with the
      standard set by Iranian Environmental Protection Agency for discharge to surface
      water resources. Gathered Data showed that many of these parameters, including
      Oil, BOD5, COD, Turbidity, PO43-, SO42-, TSS, in effluent of industrials are
      higher than the permitted amount. Therefore, regarding discharge of the to the
      surface water (seawater) and in accordance with Environment Protection Agency
      standards for effluent disposal, it should be purified to about 90% prior to
      discharge. Due to high concentration of solutes in petrochemical wastewater, it
      is not possible to use it for agricultural purpose. In this data, due to ethical
      considerations, we did not mention the name of petrochemical complex.

PMID- 30225330
TI  - Widespread hyperpigmented rash present for 1 year.

PMID- 30225331
TI  - Unilateral reticulated patch localized to the anterior thigh.

PMID- 30225332
TI  - Diffuse pruritic papules.

PMID- 30225333
TI  - Case of pulmonary benign metastasizing leiomyoma from synchronous uterine
      leiomyoma in a postmenopausal woman.
AB  - Benign metastasizing leiomyoma (BML) is a rare tumor comprising histologically
      benign smooth muscle cells and exhibits the same histological findings as a
      uterine myoma although in an extra-uterine location. Most BMLs occur several
      years after surgery for uterine myoma in women of reproductive age. Here, we
      report a case of pulmonary BML in a 54-year-old postmenopausal woman with no
      previous history of myomectomy or hysterectomy. The patient presented with a
      rapid increase in abdominal girth over the past 3 months and a cough lasting for
      2 months. Chest computed tomography (CT) revealed multiple pulmonary nodules,
      ranging in diameter from a few millimeters to 1.5 cm. Abdominal CT revealed a
      well-defined heterogeneous hypervascular uterine mass measuring 25 cm at the
      widest diameter. In addition to the uterine mass, imaging studies identified no
      other origin of the metastatic lung nodules. Total abdominal hysterectomy and
      bilateral salpingo-oophorectomy were performed followed by video-assisted
      thoracoscopy. The histological findings of the lungs and uterus suggested myoma.
      The patient remains asymptomatic and disease-free at 7 years after surgery
      without adjuvant treatment.

PMID- 30225334
TI  - Sebaceous carcinoma arising within an ovarian mature cystic teratoma: A case
      report with discussion of clinical management and genetic evaluation.
AB  - Sebaceous carcinomas are rare tumors, with the majority of described cases
      occurring within the eyelid. To date, there are nine documented reports of
      sebaceous carcinoma arising within a mature cystic teratoma of the ovary.
      Although the majority of cases originate from idiopathic mutations, there exists
      a strong association between this rare tumor and hereditary syndromes of DNA
      mismatch repair deficiency, such as Lynch syndrome and the lesser-known Muir
      Torre syndrome. Here we present the case of a 67 year-old woman with a
      longstanding history of a small left ovarian cyst with sonographic features of an
      ovarian dermoid. After nine years, the left adnexal mass was noted to have
      enlarged, and she underwent a laparoscopic bilateral salpingo-oophorectomy. The
      final pathology was reported as sebaceous carcinoma arising within a mature
      cystic teratoma. The patient underwent subsequent surgical staging and has been
      followed for eight months without evidence of disease. This report includes a
      review of the current literature, as well as a brief discussion of the clinical
      management of women with sebaceous carcinoma arising within a mature teratoma.
      Additionally, we comment on the broader, hereditary significance of a diagnosis
      of sebaceous carcinoma, and use this case to demonstrate the thorough histologic
      and genetic evaluation that is recommended for patients diagnosed with this rare
      tumor.

PMID- 30225335
TI  - Building the case for housing policy: Understanding public beliefs about housing
      affordability as a key social determinant of health.
AB  - Background: The current housing crisis in the U.S. requires the consideration and
      promotion of policies that improve the circumstances of severe housing cost
      burdens. Building public awareness of the health impacts associated with housing
      affordability may be a key prerequisite for policy change. Methods: Quantitative
      and qualitative data from a national survey were used to investigate public
      understandings about housing affordability as a key driver of health.
      Quantitative and qualitative findings were integrated to test whether any
      relationships existed between respondents' considerations and concerns about
      housing affordability and their perceptions about housing affordability as a
      social determinant of health. Findings: These data support four key findings.
      First, understandings of the relationship between affordable housing and health
      are partisan and income-based driven, with Republicans and high-income
      respondents less likely to acknowledge the effects of housing affordability on
      health. Second, varied frames of communication about the relationship between
      housing affordability and health may produce significantly different reactions
      among political and income subgroups.Third, while there is considerable agreement
      that housing affordability promotes health when using forced-choice measures,
      connections between affordable housing and health are not readily volunteered.
      Finally, the themes of personal responsibility and stability and security
      significantly resonate with Republicans and high-income earners. Conclusions:
      Contextualizing the issue of housing affordability within various domains in ways
      that effectively resonate with the American public and policymakers and across
      political and income spectra, is highly imperative.

PMID- 30225336
TI  - Socioeconomic variables explain rural disparities in US mortality rates:
      Implications for rural health research and policy.
AB  - Objectives: Rural disparities in age-adjusted mortality are growing in the United
      States. While socioeconomic variables have been found to explain significant
      variation in life expectancy across US counties, previous research has not
      examined the role of socioeconomic variables in explaining rural mortality
      disparities. The purpose of this study was to quantify the rural mortality
      disparity after controlling for socioeconomic variables. Methods: Recursive
      partitioning, or tree regression, was used to fit models predicting premature
      mortality across counties in the United States, adjusted for age, median income,
      and percent in poverty in 4 time periods (from 2004 to 2012) with and without
      inclusion of an urban-rural variable. Results: We found median income and percent
      in poverty explained about 50% of the variation in age-adjusted premature
      mortality rates across US counties in each of the four time periods. After
      controlling for these socioeconomic variables, rural mortality disparities
      largely disappeared, explaining less than 2% of the variance in premature
      mortality. Conclusions: Addressing poverty and other socioeconomic issues should
      be a priority to improve health in rural communities. Interventions designed to
      target social determinants of health in rural areas are needed to address the
      growing rural mortality disparity that is largely explained by measures of
      poverty and income. Researchers examining rural health disparities should
      routinely include socioeconomic variables in their analyses.

PMID- 30225337
TI  - Inequalities in mental health and well-being in a time of austerity: Follow-up
      findings from the Stockton-on-Tees cohort study.
AB  - In response to the 2007/8 financial crisis and the subsequent 'Great Recession',
      the UK government pursued a policy of austerity, characterised by public spending
      cuts and reductions in working-age welfare benefits. This paper reports on a case
      study of the effects of this policy on local inequalities in mental health and
      wellbeing in the local authority of Stockton-on-Tees in the North East of
      England, an area with very high spatial and socio-economic inequalities. Follow
      up findings from a prospective cohort study of the gap in mental health and
      wellbeing between the most and least deprived neighbourhoods of Stockton-on-Tees
      is presented. It is the first quantitative study to use primary data to
      intensively and longitudinally explore local inequalities in mental health and
      wellbeing during austerity and it also examines any changes in the underpinning
      social and behavioural determinants of health. Using a stratified random sampling
      technique, the data was analysed using linear mixed effects model (LMM) that
      explored any changes in the gap in mental health and wellbeing between people
      from the most and least deprived areas, alongside any changes in the material,
      psychosocial and behavioural determinants. The main findings are that the
      significant gap in mental health between the two areas remained constant over the
      18-month study period, whilst there were no changes in the underlying
      determinants. These results may reflect our relatively short follow-up period or
      the fact that the cohort sample were older than the general population and
      pensioners in the UK have largely been protected from austerity. The study
      therefore potentially provides further empirical evidence to support assertions
      that social safety nets matter - particularly in times of economic upheaval.

PMID- 30225338
TI  - Patterns, prevalence and determinants of environmental tobacco smoke exposure
      among adults in Bangladesh.
AB  - Background: Exposure to environmental tobacco smoke (ETS) has been suggested as a
      risk factor for various health problems. Thus, this study examines the patterns
      and predictors of ETS exposure among adults at home, workplace and public places.
      Methods: The dataset covered a nationally representative sample of 9629
      respondents extracted from the Global Adult Tobacco Survey. Diamond-shaped
      equiponderant graphs were used to exhibit the prevalence of ETS. In Logistic
      regressions, ETS exposure at home, workplace and public places were used as
      response variables. Demographic and socioeconomic variables, health knowledge
      about ETS, attitude towards ETS, perception of smoking restrictions were
      considered as predictors. Results: Adults in higher age groups and females were
      less exposed to ETS. Better education, high wealth status, better health
      knowledge on ETS, practice of no smoking at home, and support smoking
      restrictions were significantly associated with lower ETS exposure at home. Those
      residing in rural areas and living with many people together were more likely to
      be exposed to ETS at home. In contrast with home and workplace exposure, adults
      with higher education, better wealth status, good knowledge on ETS, and support
      smoking restrictions experienced a high level of exposure at public places.
      Interestingly, results suggest that those with high levels of ETS exposure at
      home and workplace had lower exposure to ETS in public places. Conclusions: ETS
      control should not be overlooked in public health policy. Protection from ETS at
      home is particularly important, given its impact on the attitude towards and
      awareness about ETS exposure at all places.

PMID- 30225340
TI  - Antiarrhythmic drugs for atrial fibrillation: Imminent impulses are emerging.
AB  - Rhythm and rate strategies are considered equivalent for the management of atrial
      fibrillation (AF). Moreover, both strategies are intended for improving symptoms
      and quality of life. Despite the clinical availability of several antiarrhythmic
      drugs (AAD) the alternatives for the patient with comorbidities are significantly
      fewer because of the concern regarding many adverse effects, including
      proarrhythmias. The impetuous development of AF ablation gave rise to a false
      impression that AAD are a second line therapy. All these statements reflect, in
      fact, the weakness of the classical paradigm and classification regarding AAD and
      the gap between the current knowledge of AF mechanism and determinants and the
      "classical" AAD non-discriminatory action. A new paradigm in development of
      effective and safe AAD is based on modern knowledge of vulnerable parameters
      involved in the genesis and perpetuation of AF. New AAD will target specific
      triggers of AF and ion currents which are expressed preferentially in
      fibrillatory atrium. Such targets will include repolarizing currents and
      channels, as ultrarapid potassium current, two pore potassium current, the
      acetylcholine-gated potassium current, small-conductance calcium-dependent
      potassium channels, but, also, molecular targets involved in intracellular
      calcium kinetics, as Ca2+-calmodulin-dependent protein kinase, ryanodine
      receptors and non-coding miRNA. New mechanistic discoveries link AF to
      inflammation and modern anti-cytokine drugs. There is still a long way to win
      between basic research and clinical practice, but, without any doubt,
      antiarrhythmic drug therapy will remain and develop as a cornerstone therapy for
      AF not in conflict, but complementary and alternative to interventional therapy.

PMID- 30225341
TI  - Motivation Modulates Brain Networks in Response to Faces Varying in Race and
      Status: A Multivariate Approach 3.
AB  - Previous behavioral and neuroimaging work indicates that individuals who are
      externally motivated to respond without racial prejudice tend not to
      spontaneously regulate their prejudice and prefer to focus on nonracial
      attributes when evaluating others. This fMRI multivariate analysis used partial
      least squares analysis to examine the distributed neural processing of race and a
      relevant but ostensibly nonracial attribute (i.e., socioeconomic status) as a
      function of the perceiver's external motivation. Sixty-one white male
      participants (Homo sapiens) privately formed impressions of black and white male
      faces ascribed with high or low status. Across all conditions, greater external
      motivation was associated with reduced coactivation of brain regions believed to
      support emotion regulation (rostral anterior cingulate cortex), introspection
      (middle cingulate), and social cognition (temporal pole, medial prefrontal
      cortex). The reduced involvement of this network irrespective of target race and
      status suggests that external motivation is related to the participant's overall
      approach to impression formation in an interracial context. The findings
      highlight the importance of examining network coactivation in understanding the
      role of external motivation in impression formation, among other interracial
      social processes.

PMID- 30225342
TI  - Visual Temporal Contrast Sensitivity in the Behaving Mouse Shares Fundamental
      Properties with Human Psychophysics.
AB  - The mammalian visual system has a remarkable capacity to detect differences in
      contrast across time, which is known as temporal contrast sensitivity (TCS).
      Details of the underlying neural mechanisms are rapidly emerging as a result of a
      series of elegant electrophysiological studies performed largely with the mouse
      as an experimental model. However, rigorous psychophysical methods are necessary
      to pair the electrophysiology with temporal visual behavior in mouse. The
      optomotor response is frequently used as a proxy for retinal temporal processing
      in rodents. However, subcortical reflexive pathways drive the optomotor response
      rather than cortical decision-making areas. To address this problem, we have
      developed an operant behavior assay that measures TCS in behaving mice. Mice were
      trained to perform a forced-choice visual task and were tested daily on their
      ability to distinguish flickering from nonflickering overhead lights. Correct
      responses (Hit and Correct Rejections) were rewarded. Contrast, temporal
      frequency, and mean illumination of the flicker were the independent variables.
      We validated and applied the theory of signal detection to estimate the
      discriminability factor (d'), a measure of performance that is independent of
      response bias and motivation. The empirical contrast threshold was defined as the
      contrast necessary to elicit d' = 1 and TCS as the inverse of the contrast
      threshold. With this approach, we established in the mouse a model of human
      vision that shares fundamental properties of human temporal psychophysics such as
      Weber adaptation in response to low temporal frequency flicker and illumination
      dependent increases in critical flicker frequency as predicted by the Ferry
      Porter law.

PMID- 30225339
TI  - Minimotifs dysfunction is pervasive in neurodegenerative disorders.
AB  - Minimotifs are modular contiguous peptide sequences in proteins that are
      important for posttranslational modifications, binding to other molecules, and
      trafficking to specific subcellular compartments. Some molecular functions of
      proteins in cellular pathways can be predicted from minimotif consensus sequences
      identified through experimentation. While a role for minimotifs in regulating
      signal transduction and gene regulation during disease pathogenesis (such as
      infectious diseases and cancer) is established, the therapeutic use of minimotif
      mimetic drugs is limited. In this review, we discuss a general theme identifying
      a pervasive role of minimotifs in the pathomechanism of neurodegenerative
      diseases. Beyond their longstanding history in the genetics of familial
      neurodegeneration, minimotifs are also major players in neurotoxic protein
      aggregation, aberrant protein trafficking, and epigenetic regulation.
      Generalizing the importance of minimotifs in neurodegenerative diseases offers a
      new perspective for the future study of neurodegenerative mechanisms and the
      investigation of new therapeutics.

PMID- 30225344
TI  - Tetrode Recording from the Hippocampus of Behaving Mice Coupled with Four-Point
      Irradiation Closed-Loop Optogenetics: A Technique to Study the Contribution of
      Hippocampal SWR Events to Learning.
AB  - With the advent of optogenetics, it became possible to change the activity of a
      targeted population of neurons in a temporally controlled manner. To combine the
      advantages of 60-channel in vivo tetrode recording and laser-based optogenetics,
      we have developed a closed-loop recording system that allows for the actual
      electrophysiological signal to be used as a trigger for the laser light mediating
      the optogenetic intervention. We have optimized the weight, size, and shape of
      the corresponding implant to make it compatible with the size, force, and
      movements of a behaving mouse, and we have shown that the system can efficiently
      block sharp wave ripple (SWR) events using those events themselves as a trigger.
      To demonstrate the full potential of the optogenetic recording system we present
      a pilot study addressing the contribution of SWR events to learning in a complex
      behavioral task.

PMID- 30225343
TI  - Larval Zebrafish Lateral Line as a Model for Acoustic Trauma.
AB  - Excessive noise exposure damages sensory hair cells, leading to permanent hearing
      loss. Zebrafish are a highly tractable model that have advanced our understanding
      of drug-induced hair cell death, yet no comparable model exists for noise
      exposure research. We demonstrate the utility of zebrafish as model to increase
      understanding of hair cell damage from acoustic trauma and develop protective
      therapies. We created an acoustic trauma system using underwater cavitation to
      stimulate lateral line hair cells. We found that acoustic stimulation resulted in
      exposure time- and intensity-dependent lateral line and saccular hair cell damage
      that is maximal at 48-72 h post-trauma. The number of TUNEL+ lateral line hair
      cells increased 72 h post-exposure, whereas no increase was observed in TUNEL+
      supporting cells, demonstrating that acoustic stimulation causes hair cell
      specific damage. Lateral line hair cells damaged by acoustic stimulation
      regenerate within 3 d, consistent with prior regeneration studies utilizing
      ototoxic drugs. Acoustic stimulation-induced hair cell damage is attenuated by
      pharmacological inhibition of protein synthesis or caspase activation, suggesting
      a requirement for translation and activation of apoptotic signaling cascades.
      Surviving hair cells exposed to acoustic stimulation showed signs of
      synaptopathy, consistent with mammalian studies. Finally, we demonstrate the
      feasibility of this platform to identify compounds that prevent acoustic trauma
      by screening a small redox library for protective compounds. Our data suggest
      that acoustic stimulation results in lateral line hair cell damage consistent
      with acoustic trauma research in mammals, providing a highly tractable model for
      high-throughput genetic and drug discovery studies.

PMID- 30225345
TI  - Sodium Channel-Dependent and -Independent Mechanisms Underlying Axonal
      Afterdepolarization at Mouse Hippocampal Mossy Fibers.
AB  - Action potentials propagating along axons are often followed by prolonged
      afterdepolarization (ADP) lasting for several tens of milliseconds. Axonal ADP is
      thought to be an important factor in modulating the fidelity of spike propagation
      during repetitive firings. However, the mechanism as well as the functional
      significance of axonal ADP remain unclear, partly due to inaccessibility to small
      structures of axon for direct electrophysiological recordings. Here, we examined
      the ionic and electrical mechanisms underlying axonal ADP using whole-bouton
      recording from mossy fiber terminals in mice hippocampal slices. ADP following
      axonal action potentials was strongly enhanced by focal application of
      veratridine, an inhibitor of Na+ channel inactivation. In contrast, tetrodotoxin
      (TTX) partly suppressed ADP, suggesting that a Na+ channel-dependent component is
      involved in axonal ADP. The remaining TTX-resistant Na+ channel-independent
      component represents slow capacitive discharge reflecting the shape and
      electrical properties of the axonal membrane. We also addressed the functional
      impact of axonal ADP on presynaptic function. In paired-pulse stimuli, we found
      that axonal ADP minimally affected the peak height of subsequent action
      potentials, although the rising phase of action potentials was slightly slowed,
      possibly due to steady-state inactivation of Na+ channels by prolonged
      depolarization. Voltage clamp analysis of Ca2+ current elicited by action
      potential waveform commands revealed that axonal ADP assists short-term
      facilitation of Ca2+ entry into the presynaptic terminals. Taken together, these
      data show that axonal ADP maintains reliable firing during repetitive stimuli and
      plays important roles in the fine-tuning of short-term plasticity of transmitter
      release by modulating Ca2+ entry into presynaptic terminals.

PMID- 30225347
TI  - Differential Involvement of Kinase Activity of Ca2+/Calmodulin-Dependent Protein
      Kinase IIalpha in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase
      Dead Knock-In Mouse.
AB  - Ca2+/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) is a key mediator
      of activity-dependent neuronal modifications and has been implicated in the
      molecular mechanisms of learning and memory. Indeed, several types of CaMKIIalpha
      knock-in (KI) and knock-out (KO) mice revealed impairments in hippocampal
      synaptic plasticity and behavioral learning. On the other hand, a similar role
      for CaMKIIalpha has been implicated in amygdala-dependent memory, but detailed
      analyses have not much been performed yet. To better understand its involvement
      in amygdala-dependent memory as compared to hippocampus-dependent memory, here we
      performed biochemical analyses and behavioral memory tests using the kinase-dead
      CaMKIIalpha (K42R)-KI mouse. In the Morris water maze tasks, homozygous mutants
      performed well in the visible platform trials, while they failed to form spatial
      memory in the hippocampus-dependent hidden platform trials. In fear conditioning,
      these mice were impaired but showed a certain level of amygdala-dependent cued
      fear memory, which lasted four weeks, while they showed virtually no hippocampus
      dependent context discrimination. Neither stronger stimulation nor repetitive
      stimulation compensated for their memory deficits. The differential outcome of
      hippocampus- and amygdala-dependent memory in the mutant mouse was not due to
      differential expression of CaMKIIalpha between the hippocampus and the amygdala,
      because biochemical analyses revealed that both kinase activity and protein
      levels of CaMKII were indistinguishable between the two brain regions. These
      results indicate that kinase activity of CaMKIIalpha is indispensable for
      hippocampus-dependent memory, but not necessarily for amygdala-dependent memory.
      There may be a secondary, CaMKIIalpha activity-independent pathway, in addition
      to the CaMKIIalpha activity-dependent pathway, in the acquisition of amygdala
      dependent memory.

PMID- 30225346
TI  - Immediate-Early Promoter-Driven Transgenic Reporter System for Neuroethological
      Research in a Hemimetabolous Insect.
AB  - Genes expressed in response to increased neuronal activity are widely used as
      activity markers in recent behavioral neuroscience. In the present study, we
      established transgenic reporter system for whole-brain activity mapping in the
      two-spotted cricket Gryllus bimaculatus, a hemimetabolous insect used in
      neuroethology and behavioral ecology. In the cricket brain, a homolog of early
      growth response-1 (Gryllus egr-B) was rapidly induced as an immediate-early gene
      (IEG) in response to neuronal hyperexcitability. The upstream genomic fragment of
      Gryllus egr-B contains potential binding sites for transcription factors
      regulated by various intracellular signaling pathways, as well as core promoter
      elements conserved across insect/crustacean egr-B homologs. Using the upstream
      genomic fragment of Gryllus egr-B, we established an IEG promoter-driven
      transgenic reporter system in the cricket. In the brain of transgenic crickets,
      the reporter gene (a nuclear-targeted destabilized EYFP) was induced in response
      to neuronal hyperexcitability. Inducible expression of reporter protein was
      detected in almost all neurons after neuronal hyperexcitability. Using our novel
      reporter system, we successfully detected neuronal activation evoked by feeding
      in the cricket brain. Our IEG promoter-driven activity reporting system allows us
      to visualize behaviorally relevant neural circuits at cellular resolution in the
      cricket brain.

PMID- 30225348
TI  - Spike-Conducting Integrate-and-Fire Model.
AB  - Modeling is a useful tool for investigating various biophysical characteristics
      of neurons. Recent simulation studies of propagating action potentials (spike
      conduction) along axons include the investigation of neuronal activity evoked by
      electrical stimulation from implantable prosthetic devices. In contrast to point
      neuron simulations, where a large variety of models are readily available,
      Hodgkin-Huxley-type conductance-based models have been almost the only option for
      simulating axonal spike conduction, as simpler models cannot faithfully replicate
      the waveforms of propagating spikes. Since the amount of available physiological
      data, especially in humans, is usually limited, calibration, and justification of
      the large number of parameters of a complex model is generally difficult. In
      addition, not all simulation studies of axons require detailed descriptions of
      nonlinear ionic dynamics. In this study, we construct a simple model of spike
      generation and conduction based on the exponential integrate-and-fire model,
      which can simulate the rapid growth of the membrane potential at spike
      initiation. In terms of the number of parameters and equations, this model is
      much more compact than conventional models, but can still reliably simulate spike
      conduction along myelinated and unmyelinated axons that are stimulated
      intracellularly or extracellularly. Our simulations of auditory nerve fibers with
      this new model suggest that, because of the difference in intrinsic membrane
      properties, the axonal spike conduction of high-frequency nerve fibers is faster
      than that of low-frequency fibers. The simple model developed in this study can
      serve as a computationally efficient alternative to more complex models for
      future studies, including simulations of neuroprosthetic devices.

PMID- 30225349
TI  - State-Dependent Modification of Sensory Sensitivity via Modulation of
      Backpropagating Action Potentials.
AB  - Neuromodulators play a critical role in sensorimotor processing via various
      actions, including pre- and postsynaptic signal modulation and direct modulation
      of signal encoding in peripheral dendrites. Here, we present a new mechanism that
      allows state-dependent modulation of signal encoding in sensory dendrites by
      neuromodulatory projection neurons. We studied the impact of antidromic action
      potentials (APs) on stimulus encoding using the anterior gastric receptor (AGR)
      neuron in the heavily modulated crustacean stomatogastric ganglion (STG). We
      found that ectopic AP initiation in AGR's axon trunk is under direct
      neuromodulatory control by the inferior ventricular (IV) neurons, a pair of
      descending projection neurons. IV neuron activation elicited a long-lasting
      decrease in AGR ectopic activity. This modulation was specific to the site of AP
      initiation and could be mimicked by focal application of the IV neuron co
      transmitter histamine. IV neuron actions were diminished after blocking H2
      receptors in AGR's axon trunk, suggesting a direct axonal modulation. This local
      modulation did not affect the propagation dynamics of en passant APs. However,
      decreases in ectopic AP frequency prolonged sensory bursts elicited distantly
      near AGR's dendrites. This frequency-dependent effect was mediated via the
      reduction of antidromic APs, and the diminishment of backpropagation into the
      sensory dendrites. Computational models suggest that invading antidromic APs
      interact with local ionic conductances, the rate constants of which determine the
      sign and strength of the frequency-dependent change in sensory sensitivity.
      Antidromic APs therefore provide descending projection neurons with a means to
      influence sensory encoding without affecting AP propagation or stimulus
      transduction.

PMID- 30225350
TI  - Prospective Analysis of the Effects of Maternal Immune Activation on Rat
      Cytokines during Pregnancy and Behavior of the Male Offspring Relevant to
      Schizophrenia.
AB  - Influenza during pregnancy is associated with the development of psychopathology
      in the offspring. We sought to determine whether maternal cytokines produced
      following administration of viral mimetic polyinosinic-polycytidylic acid
      (polyI:C) to pregnant rats were predictive of behavioral abnormalities in the
      adult offspring. Timed-pregnant Sprague Dawley rats received a single intravenous
      injection of 4-mg/kg polyI:C or saline on gestational day (GD)15. Blood was
      collected 3 h later for serum analysis of cytokine levels with ELISA. Male
      offspring were tested in a battery of behavioral tests during adulthood and
      behavior was correlated with maternal cytokine levels. Maternal serum levels of
      CXCL1 and interleukin (IL)-6, but not tumor necrosis factor (TNF)-alpha or CXCL2,
      were elevated in polyI:C-treated dams. PolyI:C-treated dams experienced post
      treatment weight loss and polyI:C pups were smaller than controls at postnatal
      day (PND)1. Various behavior alterations were seen in the polyI:C-treated
      offspring. Male polyI:C offspring had enhanced MK-801-induced locomotion, and
      reduced sociability. PolyI:C offspring failed to display crossmodal and visual
      memory, and oddity preference was also impaired. Set-shifting, assessed with a
      lever-based operant conditioning task, was facilitated while touchscreen-based
      reversal learning was impaired. Correlations were found between maternal serum
      concentrations of CXCL1, acute maternal temperature and body weight changes,
      neonatal pup mass, and odd object discrimination and social behavior. Overall,
      while the offspring of polyI:C-treated rats displayed behavior abnormalities,
      maternal serum cytokines were not related to the long-term behavior changes in
      the offspring. Maternal sickness effects and neonatal pup size may be better
      indicators of later effects of maternal inflammation in the offspring.

PMID- 30225351
TI  - Deciphering the Contribution of Oriens-Lacunosum/Moleculare (OLM) Cells to
      Intrinsic theta Rhythms Using Biophysical Local Field Potential (LFP) Models.
AB  - Oscillations in local field potentials (LFPs) are prevalent and contribute to
      brain function. An understanding of the cellular correlates and pathways
      affecting LFPs is needed, but many overlapping pathways in vivo make this
      difficult to achieve. A prevalent LFP rhythm in the hippocampus associated with
      memory processing and spatial navigation is the theta (3-12 Hz) oscillation.
      theta rhythms emerge intrinsically in an in vitro whole hippocampus preparation
      and this reduced preparation makes it possible to assess the contribution of
      different cell types to LFP generation. We focus on oriens-lacunosum/moleculare
      (OLM) cells as a major class of interneurons in the hippocampus. OLM cells can
      influence pyramidal (PYR) cells through two distinct pathways: by direct
      inhibition of PYR cell distal dendrites, and by indirect disinhibition of PYR
      cell proximal dendrites. We use previous inhibitory network models and build
      biophysical LFP models using volume conductor theory. We examine the effect of
      OLM cells to ongoing intrinsic LFP theta rhythms by directly comparing our model
      LFP features with experiment. We find that OLM cell inputs regulate the
      robustness of LFP responses without affecting their average power and that this
      robust response depends on coactivation of distal inhibition and basal
      excitation. We use our models to estimate the spatial extent of the region
      generating LFP theta rhythms, leading us to predict that about 22,000 PYR cells
      participate in intrinsic theta generation. Besides obtaining an understanding of
      OLM cell contributions to intrinsic LFP theta rhythms, our work can help decipher
      cellular correlates of in vivo LFPs.

PMID- 30225352
TI  - Discharge and Role of Acetylcholine Pontomesencephalic Neurons in Cortical
      Activity and Sleep-Wake States Examined by Optogenetics and Juxtacellular
      Recording in Mice.
AB  - Acetylcholine (ACh) neurons in the pontomesencephalic tegmentum (PMT) are thought
      to play an important role in promoting cortical activation with waking (W) and
      paradoxical sleep [PS; or rapid eye movement (REM)], but have yet to be proven to
      do so by selective stimulation and simultaneous recording of identified ACh
      neurons. Here, we employed optogenetics combined with juxtacellular recording and
      labeling of neurons in transgenic (TG) mice expressing ChR2 in choline
      acetyltransferase (ChAT)-synthesizing neurons. We established in vitro then in
      vivo in anesthetized (A) and unanesthetized (UA), head-fixed mice that
      photostimulation elicited a spike with short latency in neurons which could be
      identified by immunohistochemical staining as ACh neurons within the laterodorsal
      (LDT)/sublaterodorsal (SubLDT) and pedunculopontine tegmental (PPT) nuclei.
      Continuous light pulse stimulation during sleep evoked tonic spiking by ACh
      neurons that elicited a shift from irregular slow wave activity to rhythmic theta
      and enhanced gamma activity on the cortex without behavioral arousal. With theta
      frequency rhythmic light pulse stimulation, ACh neurons discharged in bursts that
      occurred in synchrony with evoked cortical theta. During natural sleep-wake
      states, they were virtually silent during slow wave sleep (SWS), discharged in
      bursts during PS and discharged tonically during W. Yet, their bursting during PS
      was not rhythmic or synchronized with cortical theta but associated with phasic
      whisker movements. We conclude that ACh PMT neurons promote theta and gamma
      cortical activity during W and PS by their tonic or phasic discharge through
      release of ACh onto local neurons within the PMT and/or more distant targets in
      the hypothalamus and thalamus.

PMID- 30225353
TI  - The Nogo Receptor Ligand LGI1 Regulates Synapse Number and Synaptic Activity in
      Hippocampal and Cortical Neurons.
AB  - Leucine-rich glioma-inactivated protein 1 (LGI1) is a secreted neuronal protein
      and a Nogo receptor 1 (NgR1) ligand. Mutations in LGI1 in humans causes autosomal
      dominant lateral temporal lobe epilepsy and homozygous deletion of LGI1 in mice
      results in severe epileptic seizures that cause early postnatal death. NgR1 plays
      an important role in the development of CNS synapses and circuitry by limiting
      plasticity in the adult cortex via the activation of RhoA. These relationships
      and functions prompted us to examine the effect of LGI1 on synapse formation in
      vitro and in vivo. We report that application of LGI1 increases synaptic density
      in neuronal culture and that LGI1 null hippocampus has fewer dendritic mushroom
      spines than in wild-type (WT) littermates. Further, our electrophysiological
      investigations demonstrate that LGI1 null hippocampal neurons possess fewer and
      weaker synapses. RhoA activity is significantly increased in cortical cultures
      derived from LGI1 null mice and using a reconstituted system; we show directly
      that LGI1 antagonizes NgR1-tumor necrosis factor receptor orphan Y (TROY)
      signaling. Our data suggests that LGI1 enhances synapse formation in cortical and
      hippocampal neurons by reducing NgR1 signaling.

PMID- 30225354
TI  - Ser46-Phosphorylated MARCKS Is a Marker of Neurite Degeneration at the Pre
      aggregation Stage in PD/DLB Pathology.
AB  - Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS)
      reflects neurite degeneration at the early stage of Alzheimer's disease (AD),
      before extracellular Abeta aggregates are histologically detectable. Here, we
      demonstrate that similar changes in MARCKS occur in Parkinson's disease (PD) and
      dementia with Lewy bodies (DLB) pathologies in both mouse models and human
      patients. The increase in the level of pSer46-MARCKS began before alpha-synuclein
      aggregate formation, at a time when human alpha-Syn-BAC-Tg/GBA-hetero-KO mice
      exhibited no symptoms, and was sustained during aging, consistent with the
      pattern in human postmortem brains. The results strongly imply a common mechanism
      of pre-aggregation neurite degeneration in AD and PD/DLB pathologies.

PMID- 30225355
TI  - Two Sides of the Same Coin: Distinct Sub-Bands in the alpha Rhythm Reflect
      Facilitation and Suppression Mechanisms during Auditory Anticipatory Attention.
AB  - Anticipatory attention results in enhanced response to task-relevant stimulus,
      and reduced processing of unattended input, suggesting the deployment of distinct
      facilitatory and suppressive mechanisms. alpha Oscillations are a suitable
      candidate for supporting these mechanisms. We aimed to examine the role of alpha
      oscillations, with a special focus on peak frequencies, in facilitatory and
      suppressive mechanisms during auditory anticipation, within the auditory and
      visual regions. Magnetoencephalographic (MEG) data were collected from fourteen
      healthy young human adults (eight female) performing an auditory task in which
      spatial attention to sounds was manipulated by visual cues, either informative or
      not of the target side. By incorporating uninformative cues, we could delineate
      facilitating and suppressive mechanisms. During anticipation of a visually-cued
      auditory target, we observed a decrease in alpha power around 9 Hz in the
      auditory cortices; and an increase around 13 Hz in the visual regions. Only this
      power increase in high alpha significantly correlated with behavior. Importantly,
      within the right auditory cortex, we showed a larger increase in high alpha power
      when attending an ipsilateral sound; and a stronger decrease in low alpha power
      when attending a contralateral sound. In summary, we found facilitatory and
      suppressive attentional mechanisms with distinct timing in task-relevant and task
      irrelevant brain areas, differentially correlated to behavior and supported by
      distinct alpha sub-bands. We provide new insight into the role of the alpha peak
      frequency by showing that anticipatory attention is supported by distinct
      facilitatory and suppressive mechanisms, mediated in different low and high sub
      bands of the alpha rhythm, respectively.

PMID- 30225356
TI  - Early Targeting of L-Selectin on Leukocytes Promotes Recovery after Spinal Cord
      Injury, Implicating Novel Mechanisms of Pathogenesis.
AB  - L-selectin, a lectin-like receptor on all leukocyte classes, functions in
      adhesive and signaling roles in the recruitment of myeloid cells from the blood
      to sites of inflammation. Here, we consider L-selectin as a determinant of
      neurological recovery in a murine model of spinal cord injury (SCI). Spinal cord
      injured, L-selectin knock-out (KO) mice (male) showed improved long-term recovery
      with greater white matter sparing relative to wild-type (WT) mice and reduced
      oxidative stress in the injured cord at 72 h post-SCI. There was a partial and
      transient reduction in accumulation of neutrophils in the injured spinal cords of
      KOs at 24 h post-injury. To complement these findings with KO mice, we sought a
      pharmacologic means for lowering L-selectin levels. We found that diclofenac, a
      nonsteroidal anti-inflammatory drug (NSAID), induced the shedding of L-selectin
      from the cell surface of myeloid subsets, specifically neutrophils and non
      classical monocytes, in the blood and the injured spinal cord. Diclofenac
      administration to injured WT mice enhanced neurological recovery to a level
      comparable to that of KOs but did not improve recovery in KOs. While diclofenac
      treatment had no effect on myeloid cell accumulation, there was a reduction in
      oxidative stress at 72 h post-SCI. These findings implicate L-selectin in
      secondary pathogenesis beyond a role in leukocyte recruitment and raise the
      possibility of repurposing diclofenac for the treatment of SCI.

PMID- 30225357
TI  - A Brain without Brakes: Reduced Inhibition Is Associated with Enhanced but
      Dysregulated Plasticity in the Aged Rat Auditory Cortex.
AB  - During early developmental windows known as critical periods (CPs) of plasticity,
      passive alterations in the quality and quantity of sensory inputs are sufficient
      to induce profound and long-lasting distortions in cortical sensory
      representations. With CP closure, those representations are stabilized, a process
      requiring the maturation of inhibitory networks and the maintenance of sufficient
      GABAergic tone in the cortex. In humans and rodents, however, cortical inhibition
      progressively decreases with advancing age, raising the possibility that the
      regulation of plasticity could be altered in older individuals. Here we tested
      the hypothesis that aging results in a destabilization of sensory representations
      and maladaptive dysregulated plasticity in the rat primary auditory cortex (A1).
      Consistent with this idea, we found that passive tone exposure is sufficient to
      distort frequency tuning in the A1 of older but not younger adult rats. However,
      we also found that these passive distortions decayed rapidly, indicating an
      ongoing instability of A1 tuning in the aging cortex. These changes were
      associated with a decrease in GABA neurotransmitter concentration and a reduction
      in parvalbumin and perineuronal net expression in the cortex. Finally, we show
      that artificially increasing GABA tone in the aging A1 is sufficient to restore
      representational stability and improve the retention of learning.

PMID- 30225358
TI  - Human Rapid Eye Movement Sleep Shows Local Increases in Low-Frequency
      Oscillations and Global Decreases in High-Frequency Oscillations Compared to
      Resting Wakefulness.
AB  - It is often assumed that during rapid eye movement (REM) sleep the cerebral
      cortex homogenously shows electroencephalogram (EEG) activity highly similar to
      wakefulness. However, to date no studies have compared neural oscillatory
      activity in human REM sleep to resting wakefulness with high spatial sampling. In
      the current study, we evaluated high-resolution topographical changes in neural
      oscillatory power between both early and late naturalistic REM sleep and resting
      wakefulness in adult humans. All-night recordings with 256-channel high-density
      EEG (hd-EEG) were collected in healthy volunteers (N = 12). Topographic analysis
      revealed that, compared to wake, both the first and last cycle of REM sleep were
      associated with increased low-frequency oscillations in local central and
      occipital regions. In contrast, high-frequency activity in both alpha and beta
      bands (8-20 Hz) was globally decreased during both early and late REM sleep
      cycles compared to wakefulness. No significant differences in topographic power
      in any frequency band were observed between REM sleep cycles occurring early and
      late in the night. We replicated these findings in an independent dataset (N =
      33). Together, our findings show that human REM sleep shows consistent
      topographical changes in oscillatory power across both early and late sleep
      cycles compared to resting wakefulness.

PMID- 30225359
TI  - Myelination of Axons Corresponds with Faster Transmission Speed in the Prefrontal
      Cortex of Developing Male Rats.
AB  - Myelination of prefrontal circuits during adolescence is thought to lead to
      enhanced cognitive processing and improved behavioral control. However, while
      standard neuroimaging techniques commonly used in human and animal studies can
      measure large white matter bundles and residual conduction speed, they cannot
      directly measure myelination of individual axons or how fast electrical signals
      travel along these axons. Here we focused on a specific population of prefrontal
      axons to directly measure conduction velocity and myelin microstructure in
      developing male rats. An in vitro electrophysiological approach enabled us to
      isolate monosynaptic projections from the anterior branches of the corpus
      callosum (corpus callosum-forceps minor, CCFM) to the anterior cingulate
      subregion of the medial prefrontal cortex (Cg1) and to measure the speed and
      direction of action potentials propagating along these axons. We found that a
      large number of axons projecting from the CCFM to neurons in Layer V of Cg1 are
      ensheathed with myelin between pre-adolescence [postnatal day (PD)15] and mid
      adolescence (PD43). This robust increase in axonal myelination is accompanied by
      a near doubling of transmission speed. As there was no age difference in the
      diameter of these axons, myelin is likely the driving force behind faster
      transmission of electrical signals in older animals. These developmental changes
      in axonal microstructure and physiology may extend to other axonal populations as
      well, and could underlie some of the improvements in cognitive processing between
      childhood and adolescence.

PMID- 30225360
TI  - AhR Deletion Promotes Aberrant Morphogenesis and Synaptic Activity of Adult
      Generated Granule Neurons and Impairs Hippocampus-Dependent Memory.
AB  - Newborn granule cells are continuously produced in the subgranular zone of
      dentate gyrus throughout life. Once these cells mature, they integrate into pre
      existing circuits modulating hippocampus-dependent memory. Subsequently,
      mechanisms controlling generation and maturation of newborn cells are essential
      for proper hippocampal function. Therefore, we have studied the role of aryl
      hydrocarbon receptor (AhR), a ligand-activated bHLH-PAS transcription factor, in
      hippocampus-dependent memory and granule neuronal morphology and function using
      genetic loss-of-function approaches based on constitutive and inducible-nestin
      AhR-/- mice. The results presented here show that the impaired hippocampus
      dependent memory in AhR absence is not due to its effects on neurogenesis but to
      aberrant dendritic arborization and an increased spine density, albeit with a
      lower number of mature mushrooms spines in newborn granule cells, a finding that
      is associated with an immature electrophysiological phenotype. Together, our data
      strongly suggest that AhR plays a pivotal role in the regulation of hippocampal
      function, by controlling hippocampal granule neuron morphology and synaptic
      maturation.

PMID- 30225361
TI  - Parallel Arousal Pathways in the Lateral Hypothalamus.
AB  - Until recently, hypocretin (Hcrt) neurons were the only known wake-promoting
      neuronal population in the lateral hypothalamus (LH), but subpopulations of
      inhibitory neurons in this area and glutamatergic neurons in the nearby
      supramammillary nucleus (SuM) have recently been found that also promote
      wakefulness. We performed chemogenetic excitation of LH neurons in mice and
      observed increased wakefulness that lasted more than 4 h without unusual behavior
      or EEG anomalies. The increased wakefulness was similar in the presence or
      absence of the dual orexin receptor blocker almorexant (ALM). Analysis of hM3Dq
      transfection and c-FOS expression in LH inhibitory neurons and in the SuM failed
      to confirm that the increased wakefulness was due to these wake-promoting
      populations, although this possibility cannot be completely excluded. To evaluate
      the relationship to the Hcrt system, we repeated the study in Orexin-tTA mice in
      the presence or absence of dietary doxycycline (DOX), which enabled us to
      manipulate the percentage of Hcrt neurons that expressed hM3Dq. In DOX-fed mice,
      18% of Hcrt neurons as well as many other LH neurons expressed hM3Dq; these mice
      showed a profound increase in wake after hM3Dq activation even in the presence of
      ALM. In mice switched to normal chow, 62% of Hcrt neurons expressed hM3Dq along
      with other LH cells; chemogenetic activation produced even more sustained arousal
      which could be reduced to previous levels by ALM treatment. Together, these
      results indicate an LH neuron population that promotes wakefulness through an
      Hcrt-independent pathway that can act synergistically with the Hcrt system to
      prolong arousal.

PMID- 30225362
TI  - Evidence against the Detectability of a Hippocampal Place Code Using Functional
      Magnetic Resonance Imaging.
AB  - Individual hippocampal neurons selectively increase their firing rates in
      specific spatial locations. As a population, these neurons provide a decodable
      representation of space that is robust against changes to sensory- and path
      related cues. This neural code is sparse and distributed, theoretically rendering
      it undetectable with population recording methods such as functional magnetic
      resonance imaging (fMRI). Existing studies nonetheless report decoding spatial
      codes in the human hippocampus using such techniques. Here we present results
      from a virtual navigation experiment in humans in which we eliminated visual- and
      path-related confounds and statistical limitations present in existing studies,
      ensuring that any positive decoding results would represent a voxel-place code.
      Consistent with theoretical arguments derived from electrophysiological data and
      contrary to existing fMRI studies, our results show that although participants
      were fully oriented during the navigation task, there was no statistical evidence
      for a place code.

PMID- 30225363
TI  - Neural Pattern Classification Tracks Transfer-Appropriate Processing in Episodic
      Memory.
AB  - The transfer-appropriate processing (TAP) account holds that episodic memory
      depends on the overlap between encoding and retrieval processing. In the current
      study, we employed multivariate pattern analysis (MVPA) of electroencephalography
      to examine the relevance of spontaneously engaged visual processing during
      encoding for later retrieval. Human participants encoded word-picture
      associations, where the picture could be a famous face, a landmark, or an object.
      At test, we manipulated the retrieval demands by asking participants to retrieve
      either visual or verbal information about the pictures. MVPA revealed
      classification between picture categories during early perceptual stages of
      encoding (~170 ms). Importantly, these visual category-specific neural patterns
      were predictive of later episodic remembering, but the direction of the
      relationship was contingent on the particular retrieval demand of the memory
      task: a benefit for the visual and a cost for the verbal. A reinstatement of the
      category-specific neural patterns established during encoding was observed during
      retrieval, and again the relationship with behavior varied with retrieval
      demands. Reactivation of visual representations during retrieval was associated
      with better memory in the visual task, but with lower performance in the verbal
      task. Our findings support and extend the TAP account by demonstrating that
      processing of particular aspects during memory formation can also have
      detrimental effects on later episodic remembering when other aspects of the event
      are called-for and shed new light on encoding and retrieval interactions in
      episodic memory.

PMID- 30225364
TI  - Disordered skyrmion phase stabilized by magnetic frustration in a chiral magnet.
AB  - Magnetic skyrmions are vortex-like topological spin textures often observed to
      form a triangular-lattice skyrmion crystal in structurally chiral magnets with
      the Dzyaloshinskii-Moriya interaction. Recently, beta-Mn structure-type Co-Zn-Mn
      alloys were identified as a new class of chiral magnet to host such skyrmion
      crystal phases, while beta-Mn itself is known as hosting an elemental
      geometrically frustrated spin liquid. We report the intermediate composition
      system Co7Zn7Mn6 to be a unique host of two disconnected, thermal-equilibrium
      topological skyrmion phases; one is a conventional skyrmion crystal phase
      stabilized by thermal fluctuations and restricted to exist just below the
      magnetic transition temperature Tc, and the other is a novel three-dimensionally
      disordered skyrmion phase that is stable well below Tc. The stability of this new
      disordered skyrmion phase is due to a cooperative interplay between the chiral
      magnetism with the Dzyaloshinskii-Moriya interaction and the frustrated magnetism
      inherent to beta-Mn.

PMID- 30225365
TI  - Quantum interference of topological states of light.
AB  - Topological insulators are materials that have a gapped bulk energy spectrum but
      contain protected in-gap states appearing at their surface. These states exhibit
      remarkable properties such as unidirectional propagation and robustness to noise
      that offer an opportunity to improve the performance and scalability of quantum
      technologies. For quantum applications, it is essential that the topological
      states are indistinguishable. We report high-visibility quantum interference of
      single-photon topological states in an integrated photonic circuit. Two
      topological boundary states, initially at opposite edges of a coupled waveguide
      array, are brought into proximity, where they interfere and undergo a
      beamsplitter operation. We observe Hong-Ou-Mandel interference with 93.1 +/- 2.8%
      visibility, a hallmark nonclassical effect that is at the heart of linear optics
      based quantum computation. Our work shows that it is feasible to generate and
      control highly indistinguishable single-photon topological states, opening
      pathways to enhanced photonic quantum technology with topological properties, and
      to study quantum effects in topological materials.

PMID- 30225366
TI  - High electrical conductivity and carrier mobility in oCVD PEDOT thin films by
      engineered crystallization and acid treatment.
AB  - Air-stable, lightweight, and electrically conductive polymers are highly desired
      as the electrodes for next-generation electronic devices. However, the low
      electrical conductivity and low carrier mobility of polymers are the key
      bottlenecks that limit their adoption. We demonstrate that the key to addressing
      these limitations is to molecularly engineer the crystallization and morphology
      of polymers. We use oxidative chemical vapor deposition (oCVD) and hydrobromic
      acid treatment as an effective tool to achieve such engineering for conducting
      polymer poly(3,4-ethylenedioxythiophene) (PEDOT). We demonstrate PEDOT thin films
      with a record-high electrical conductivity of 6259 S/cm and a remarkably high
      carrier mobility of 18.45 cm2 V-1 s-1 by inducing a crystallite-configuration
      transition using oCVD. Subsequent theoretical modeling reveals a metallic nature
      and an effective reduction of the carrier transport energy barrier between
      crystallized domains in these thin films. To validate this metallic nature, we
      successfully fabricate PEDOT-Si Schottky diode arrays operating at 13.56 MHz for
      radio frequency identification (RFID) readers, demonstrating wafer-scale
      fabrication compatible with conventional complementary metal-oxide semiconductor
      (CMOS) technology. The oCVD PEDOT thin films with ultrahigh electrical
      conductivity and high carrier mobility show great promise for novel high-speed
      organic electronics with low energy consumption and better charge carrier
      transport.

PMID- 30225367
TI  - Programmable wettability on photocontrolled graphene film.
AB  - Surface materials with specific wettability play important roles in a wide
      variety of areas from science to industry. We present a novel paraffin-infused
      porous graphene film (PIPGF) with programmable wettability. Because of graphene's
      photothermal property, the paraffin in the PIPGF was in transition between liquid
      and solid in response to near-infrared (NIR) light irradiation. Thus, we imparted
      the film with a dynamic and reversible transition between a slippery and a rough
      surface as the remotely tunable wettability. In addition, with the integration of
      NIR masks, the paraffin could melt at corresponding patterns on the PIPGF, which
      formed special flow pathways for the slipping droplets. Therefore, the PIPGF
      could provide programmable wettability pathways for the spatiotemporal droplet
      manipulation by flexibly changing the NIR masks. We demonstrated these
      programmable wettability pathways to not only simplify liquid handling in the
      microplates and droplet microarrays technology but also to provide distinctly
      microfluidic microreactors for different purposes, such as practical blood
      grouping diagnosis. These features indicated that the photocontrollable PIPGF
      would be amenable to a variety of applications, such as microfluidic systems,
      laboratory-on-a-chip settings, and droplet manipulations.

PMID- 30225368
TI  - Mechanically active materials in three-dimensional mesostructures.
AB  - Complex, three-dimensional (3D) mesostructures that incorporate advanced,
      mechanically active materials are of broad, growing interest for their potential
      use in many emerging systems. The technology implications range from precision
      sensing microelectromechanical systems, to tissue scaffolds that exploit the
      principles of mechanobiology, to mechanical energy harvesters that support broad
      bandwidth operation. The work presented here introduces strategies in guided
      assembly and heterogeneous materials integration as routes to complex, 3D
      microscale mechanical frameworks that incorporate multiple, independently
      addressable piezoelectric thin-film actuators for vibratory excitation and
      precise control. The approach combines transfer printing as a scheme for
      materials integration with structural buckling as a means for 2D-to-3D geometric
      transformation, for designs that range from simple, symmetric layouts to complex,
      hierarchical configurations, on planar or curvilinear surfaces. Systematic
      experimental and computational studies reveal the underlying characteristics and
      capabilities, including selective excitation of targeted vibrational modes for
      simultaneous measurements of viscosity and density of surrounding fluids. The
      results serve as the foundations for unusual classes of mechanically active 3D
      mesostructures with unique functions relevant to biosensing, mechanobiology,
      energy harvesting, and others.

PMID- 30225369
TI  - Electronic structures and unusually robust bandgap in an ultrahigh-mobility
      layered oxide semiconductor, Bi2O2Se.
AB  - Semiconductors are essential materials that affect our everyday life in the
      modern world. Two-dimensional semiconductors with high mobility and moderate
      bandgap are particularly attractive today because of their potential application
      in fast, low-power, and ultrasmall/thin electronic devices. We investigate the
      electronic structures of a new layered air-stable oxide semiconductor, Bi2O2Se,
      with ultrahigh mobility (~2.8 * 105 cm2/V?s at 2.0 K) and moderate bandgap (~0.8
      eV). Combining angle-resolved photoemission spectroscopy and scanning tunneling
      microscopy, we mapped out the complete band structures of Bi2O2Se with key
      parameters (for example, effective mass, Fermi velocity, and bandgap). The
      unusual spatial uniformity of the bandgap without undesired in-gap states on the
      sample surface with up to ~50% defects makes Bi2O2Se an ideal semiconductor for
      future electronic applications. In addition, the structural compatibility between
      Bi2O2Se and interesting perovskite oxides (for example, cuprate high-transition
      temperature superconductors and commonly used substrate material SrTiO3) further
      makes heterostructures between Bi2O2Se and these oxides possible platforms for
      realizing novel physical phenomena, such as topological superconductivity,
      Josephson junction field-effect transistor, new superconducting optoelectronics,
      and novel lasers.

PMID- 30225370
TI  - A cascade of phase transitions in an orbitally mixed half-filled Landau level.
AB  - Half-filled Landau levels host an emergent Fermi liquid that displays instability
      toward pairing, culminating in a gapped even-denominator fractional quantum Hall
      ground state. While this pairing may be probed by tuning the polarization of
      carriers in competing orbital and spin degrees of freedom, sufficiently high
      quality platforms offering such tunability remain few. We explore the ground
      states at filling factor nu = 5/2 in ZnO-based two-dimensional electron systems
      through a forced intersection of opposing spin branches of Landau levels taking
      quantum numbers N = 1 and 0. We reveal a cascade of phases with distinct
      magnetotransport features including a gapped phase polarized in the N = 1 level
      and a compressible phase in N = 0, along with an unexpected Fermi liquid, a
      second gapped, and a strongly anisotropic nematic-like phase at intermediate
      polarizations when the levels are near degeneracy. The phase diagram is produced
      by analyzing the proximity of the intersecting levels and highlights the
      excellent reproducibility and controllability that ZnO offers for exploring
      exotic fractionalized electronic phases.

PMID- 30225371
TI  - Visible light-gated reconfigurable rotary actuation of electric nanomotors.
AB  - Highly efficient and widely applicable working mechanisms that allow
      nanomaterials and devices to respond to external stimuli with controlled
      mechanical motions could make far-reaching impact to reconfigurable, adaptive,
      and robotic nanodevices. We report an innovative mechanism that allows multifold
      reconfiguration of mechanical rotation of semiconductor nanoentities in electric
      (E) fields by visible light stimulation. When illuminated by light in the visible
      to-infrared regime, the rotation speed of semiconductor Si nanowires in E-fields
      can instantly increase, decrease, and even reverse the orientation, depending on
      the intensity of the applied light and the AC E-field frequency. This multifold
      rotational reconfiguration is highly efficient, instant, and facile. Switching
      between different modes can be simply controlled by the light intensity at an AC
      frequency. We carry out experiments, theoretical analysis, and simulations to
      understand the underlying principle, which can be attributed to the optically
      tunable polarization of Si nanowires in an aqueous suspension and an external E
      field. Finally, leveraging this newly discovered effect, we successfully
      differentiate semiconductor and metallic nanoentities in a noncontact and
      nondestructive manner. This research could inspire a new class of reconfigurable
      nanoelectromechanical and nanorobotic devices for optical sensing, communication,
      molecule release, detection, nanoparticle separation, and microfluidic
      automation.

PMID- 30225372
TI  - Correction for the Research Article: "Tailoring optical metamaterials to tune the
      atom-surface Casimir-Polder interaction" by E. A. Chan, S. A. Aljunid, G. Adamo,
      A. Laliotis, M. Ducloy, and D. Wilkowski.
AB  - [This corrects the article DOI: 10.1126/sciadv.aao4223.].

PMID- 30225375
TI  - Effects of climate change on water resources in the upper Blue Nile Basin of
      Ethiopia.
AB  - Drawing on hydrology, rainfall, and climatic data from the past 25 years, this
      article investigates the effects of climate change on water resources in the
      transnational Blue Nile Basin (BNB). The primary focus is on determining the long
      term temporal and seasonal changes in the flows of the Blue Nile in Ethiopia at
      the border to Sudan. This is important because the Blue Nile is the main
      tributary to the Nile river, the lifeline of both Sudan and Egypt. Therefore, to
      begin with long-term trends in hydrological time series were detected by means of
      both parametric and nonparametric techniques. The Soil and Water Assessment Tool
      (SWAT) model was calibrated using several sub-basins and new high-resolution land
      use and soil maps. Future climate change impacts were projected using data from
      the Climate Forecast System Reanalysis (CFSR) of the National Centers for
      Environmental Predictions based on three different climate change scenarios from
      the Coupled Model Intercomparison Project (CMIP3). Projected time series were
      analysed for changes in rainfall and streamflow trends. Climate change scenario
      modelling suggested that the precipitation will increase from 7% to 48% and that
      streamflow from the BNB could increase by 21% to 97%. The results provide a basis
      for evaluating future impacts of climate change on the upper Blue Nile River
      (Abay River). This is the main river basin contributing to the Nile and a source
      of water for millions of people in Sudan and Egypt, downstream from Ethiopia.
      Three models (CCCMA, CNRM, MRI) were applied in this research, within two future
      time periods (2046-2064 and 2081-2099) and one scenario (A1B). The Abay Basin was
      divided into seven sub-basins, six of which were used as inlets to the lowest
      basin at the border to Sudan. The above-mentioned results show that under current
      climate change scenarios there is a strong seasonal shift to be expected from the
      present main rainfall season (June to September) to an earlier onset from January
      to May with less pronounced peaks but longer duration of the rainfall season.
      This has direct consequences on the streamflow of the Blue Nile, which is
      connected to the rainfall season and therefore has direct effects on the people
      living in the sphere of influence of the Nile River.

PMID- 30225373
TI  - Comprehensive Functional Analysis of the Enterococcus faecalis Core Genome Using
      an Ordered, Sequence-Defined Collection of Insertional Mutations in Strain OG1RF.
AB  - Enterococcus faecalis is a common commensal bacterium in animal gastrointestinal
      (GI) tracts and a leading cause of opportunistic infections of humans in the
      modern health care setting. E. faecalis OG1RF is a plasmid-free strain that
      contains few mobile elements yet retains the robust survival characteristics,
      intrinsic antibiotic resistance, and virulence traits characteristic of most E.
      faecalis genotypes. To facilitate interrogation of the core enterococcal genetic
      determinants for competitive fitness in the GI tract, biofilm formation,
      intrinsic antimicrobial resistance, and survival in the environment, we generated
      an arrayed, sequence-defined set of chromosomal transposon insertions in OG1RF.
      We used an orthogonal pooling strategy in conjunction with Illumina sequencing to
      identify a set of mutants with unique, single Himar-based transposon insertions.
      The mutants contained insertions in 1,926 of 2,651 (72.6%) annotated open reading
      frames and in the majority of hypothetical protein-encoding genes and intergenic
      regions greater than 100 bp in length, which could encode small RNAs. As proof of
      principle of the usefulness of this arrayed transposon library, we created a
      minimal input pool containing 6,829 mutants chosen for maximal genomic coverage
      and used an approach that we term SMarT (sequence-defined mariner technology)
      transposon sequencing (TnSeq) to identify numerous genetic determinants of bile
      resistance in E. faecalis OG1RF. These included several genes previously
      associated with bile acid resistance as well as new loci. Our arrayed library
      allows functional screening of a large percentage of the genome with a relatively
      small number of mutants, reducing potential effects of bottlenecking, and enables
      immediate recovery of mutants following competitions. IMPORTANCE The robust
      ability of Enterococcus faecalis to survive outside the host and to spread via
      oral-fecal transmission and its high degree of intrinsic and acquired
      antimicrobial resistance all complicate the treatment of hospital-acquired
      enterococcal infections. The conserved E. faecalis core genome serves as an
      important genetic scaffold for evolution of this bacterium in the modern health
      care setting and also provides interesting vaccine and drug targets. We used an
      innovative pooling/sequencing strategy to map a large collection of arrayed
      transposon insertions in E. faecalis OG1RF and generated an arrayed library of
      defined mutants covering approximately 70% of the OG1RF genome. Then, we
      performed high-throughput transposon sequencing experiments using this library to
      determine core genomic determinants of bile resistance in OG1RF. This collection
      is a valuable resource for comprehensive, functional enterococcal genomics using
      both traditional and high-throughput approaches and enables immediate recovery of
      mutants of interest.

PMID- 30225376
TI  - Comparing causal techniques for rainfall variability analysis using causality
      algorithms in Iran.
AB  - Causal analysis (CA) is a strong quantitative approach whose mechanisms have
      climatic predictions. In this study, we studied the patterns of causality (PC) on
      the effect of rainfall (ER) using climatic series collected from 170 stations for
      the period 1975-2014 in Iran. Next, we predicted the causal relationships of
      climatic variables using causal models, including first-generation techniques
      (FGT), second-generation techniques (SGT), third-generation techniques (TGT), and
      causal hybrid techniques (CHT). Then, we estimated the causal models using
      partial squares algorithms (PSA), mechanical equations modeling algorithms (MEMA)
      such as exploratory and confirmatory methods, and spatial variability methods
      such as geostatistics and spatial statistical methods. Finally, we evaluated the
      quality of the methods using the goodness of fit indices, including absolute fit
      indices (AFI), comparative fit indices (CFI), and parsimonious fit indices (PFI).
      The results showed that CHT algorithm more suitably predicted the climatic
      spatiotemporal effect variability (SEV) by extracting direct, indirect, and total
      effects of climatic variables. Based on the CHT algorithm, the highest and lowest
      effect values were observed in total effects of winter rainfall (0.98) and summer
      rainfall variables (0.1), respectively. The SEV ranged from 0.8 to 0.98 for the
      winter rainfall total effects of CHT in Iran. Using CHT, most of the predicted
      SEV, particularly the rainfall series, displayed SEV varying from 80% to 98% of
      the winter rainfall total effects to the annual rainfall in Iran. Similarly,
      based on the CHT, the highest and lowest SEV values were in western, eastern, and
      southern regions and in central regions, respectively. In addition, the SEV
      varied within the range of 0.6-0.74 (varying from 60% to 74% for the autumn
      rainfall total effects of the annual rainfall in Iran) for the autumn rainfall
      total effects in Iran. Finally, the SEV of this type of analytical pattern as
      well as designated subject of CA applications in the atmospheric science and
      environmental science are discussed.

PMID- 30225374
TI  - Coordinated Hibernation of Transcriptional and Translational Apparatus during
      Growth Transition of Escherichia coli to Stationary Phase.
AB  - In the process of Escherichia coli K-12 growth from exponential phase to
      stationary, marked alteration takes place in the pattern of overall genome
      expression through modulation of both parts of the transcriptional and
      translational apparatus. In transcription, the sigma subunit with promoter
      recognition properties is replaced from the growth-related factor RpoD by the
      stationary-phase-specific factor RpoS. The unused RpoD is stored by binding with
      the anti-sigma factor Rsd. In translation, the functional 70S ribosome is
      converted to inactive 100S dimers through binding with the ribosome modulation
      factor (RMF). Up to the present time, the regulatory mechanisms of expression of
      these two critical proteins, Rsd and RMF, have remained totally unsolved. In this
      study, attempts were made to identify the whole set of transcription factors
      involved in transcription regulation of the rsd and rmf genes using the newly
      developed promoter-specific transcription factor (PS-TF) screening system. In the
      first screening, 74 candidate TFs with binding activity to both of the rsd and
      rmf promoters were selected from a total of 194 purified TFs. After 6 cycles of
      screening, we selected 5 stress response TFs, ArcA, McbR, RcdA, SdiA, and SlyA,
      for detailed analysis in vitro and in vivo of their regulatory roles. Results
      indicated that both rsd and rmf promoters are repressed by ArcA and activated by
      McbR, RcdA, SdiA, and SlyA. We propose the involvement of a number of TFs in
      simultaneous and coordinated regulation of the transcriptional and translational
      apparatus. By using genomic SELEX (gSELEX) screening, each of the five TFs was
      found to regulate not only the rsd and rmf genes but also a variety of genes for
      growth and survival. IMPORTANCE During the growth transition of E. coli from
      exponential phase to stationary, the genome expression pattern is altered
      markedly. For this alteration, the transcription apparatus is altered by binding
      of anti-sigma factor Rsd to the RpoD sigma factor for sigma factor replacement,
      while the translation machinery is modulated by binding of RMF to 70S ribosome to
      form inactive ribosome dimer. Using the PS-TF screening system, a number of TFs
      were found to bind to both the rsd and rmf promoters, of which the regulatory
      roles of 5 representative TFs (one repressor ArcA and the four activators McbR,
      RcdA, SdiA, and SlyA) were analyzed in detail. The results altogether indicated
      the involvement of a common set of TFs, each sensing a specific environmental
      condition, in coordinated hibernation of the transcriptional and translational
      apparatus for adaptation and survival under stress conditions.

PMID- 30225377
TI  - A possible mechanism of horseback riding on dynamic trunk alignment.
AB  - The study aimed to clarify the regularity of the motions of horse's back, rider's
      pelvis and spine associated with improvement of rider's dynamic trunk alignment.
      The study used a crossover design, with exercise using the horseback riding
      simulator (simulator hereafter) as the control condition. The experiments were
      conducted at Tokyo University of Agriculture Bio-therapy Center. The sample
      consisted of 20 healthy volunteers age 20-23 years. Participants performed 15-min
      sessions of horseback riding with a Hokkaido Pony and exercise using the
      simulator in experiments separated by >=2 weeks. Surface electromyography (EMG)
      after horseback riding revealed decreased activity in the erector spinae.
      Exploratory data analysis of acceleration and angular velocity inferred
      associations between acceleration (Rider's neck/longitudinal axis [Y hereafter])
      and angular velocity (Horse saddle/Y) as well as angular velocity (Rider's
      pelvis/Y) and angular velocity (Horse saddle/Y). Acceleration (Rider's neck/Y)
      tended to be associated with angular velocity (Rider's pelvis/Y). Surface EMG
      following exercise revealed decreased activity in the rectus abdominis and
      erector spinae after the simulator exercise. Horseback riding improved the
      rider's dynamic trunk alignment with a clear underlying mechanism, which was not
      observed with the simulator.

PMID- 30225378
TI  - Surgical considerations of marijuana use in elective procedures.
AB  - Background: Marijuana consumption is estimated as upwards of 9.5% of the U.S.
      adult population. Nevertheless, few trials exist on potential implications for
      surgical outcomes amongst users. Methods: A current literature review explored
      marijuana's effects to answer: (I) How is marijuana use screened for in clinical
      and pre-operative settings? (II) What are potential surgical complications of
      marijuana use? (III) How should surgeons handle patient marijuana use regarding
      elective surgery? (IV) Are marijuana's effects the same or different from those
      of tobacco? Results: In acute settings, marijuana's effects peaked at
      approximately 1 hour post initiation, lasting 2-4 hours. Marijuana increased
      cardiac workload, myocardial infarctions and strokes in young, chronic users.
      Cannabis caused similar pulmonary complications to those of a tobacco smoker.
      Marijuana caused airway obstruction and increased anesthetic dosages needed to
      place laryngeal airways. Use within 72 hours of general anesthesia was advised
      against. In vitro and in vivo studies were contradictory regarding prothrombic or
      antithrombotic effects. Conclusions: Marijuana use is problematic to surgeons,
      left without evidence-based approaches. In emergency settings, marijuana use may
      be unavoidable. However, further research would provide much needed information
      to guide elective procedures.

PMID- 30225379
TI  - Peripheral blood monocytes show increased osteoclast differentiation potential
      compared to bone marrow monocytes.
AB  - Bone marrow (BM) and peripheral blood (PB) derived mononuclear cells are
      precursors of in vitro osteoclast differentiation. However, few studies have
      compared the phenotypic and functional properties of osteoclasts generated from
      these sources and the effects of different growth factors on osteoclastogenesis.
      Both cell types differentiated into functional osteoclasts, but culturing the
      cells with or without transforming growth factor beta (TGF-beta) and
      dexamethasone revealed differences in their osteoclastogenic capacity. When
      receptor activator for nuclear factor kappaB ligand (RANKL) and macrophage colony
      stimulating factor (M-CSF) were used for differentiation, we did not observe
      differences in bone resorption activity or expression of osteoclastogenic genes
      calcitonin receptor (CR) and nuclear factor of activated T-cells (NFATc1) between
      the osteoclasts formed from the two sources. Addition of TGF-beta and
      dexamethasone led to higher number of nuclei in multinuclear cells and increased
      expression of tartrate resistant acid phosphatase (TRACP) 5a and 5b, CR and
      NFATc1 in PB- derived osteoclasts depicting the higher osteoclastogenic potential
      and responsiveness to TGF-beta and dexamethasone in PB monocytes. These results
      conclude that the choice of the osteoclast precursor source as well as the choice
      of osteoclastogenic growth factors are essential matters in determining the
      phenotypic characteristics of heterogeneous osteoclast populations.

PMID- 30225380
TI  - Extracellular matrix supports healing of transected rabbit Achilles tendon.
AB  - Extracellular matrix (ECM) has been intensively used in cardio surgery. The main
      goal of this research was to determine if Achilles tendon healing could be
      promoted by applying extracellular matrix scaffold (CorMatrix(r), USA). Sixteen
      (n = 16) New Zealand white mature rabbits (Oryctolagus cuniculus) were randomly
      allocated into two groups. Following complete surgical transection, rabbits in
      group A (ECM applied) (n = 8) had their Achilles tendons reconstructed using
      both, nylon suture and extracellular matrix scaffold, whereas in group B (without
      ECM) the tendons were reconstructed using nylon suture only. After four weeks,
      the rabbits were euthanized and tendon samples harvested and stained with
      hematoxylin eosin, Mallory, and Gomory and subsequently histologically analyzed
      according to modified Bonnar scale. Group B had significantly stronger
      inflammatory response, including abundant cell infiltration and
      neovascularization. In group A collagen fibers were predominantly found, whereas
      in group B reticular fibers were more abundant. Extracellular matrix scaffold has
      been found to have the real potential for promoting tendon healing through
      accelerating collagen formation, which is crucial for restoring biomechanical
      properties of a tendon, decreasing peritendineous adhesion formation, and
      reducing inflammatory edema and subsequently pain.

PMID- 30225381
TI  - Optimized dispersion quality of aqueous carbon nanotube colloids as a function of
      sonochemical yield and surfactant/CNT ratio.
AB  - In this paper, we propose and verify a theoretical model of the development of
      dispersion quality of aqueous carbon nanotube (CNT) colloid as a function of
      sonochemical yield of the sonication process. Four different surfactants; Triton
      X-100, Pluronic F-127, CTAB and SDS were studied. From these four SDS had the
      lowest dispersion performance which was surprising. Optical dispersion quality
      results fits well with proposed theoretical model.

PMID- 30225382
TI  - Next-generation and further transgenerational effects of bisphenol A on zebrafish
      reproductive tissues.
AB  - Next-generation effects and further transgenerational effects of an endocrine
      disruptor, bisphenol A (BPA), were investigated in zebrafish. The effects of BPA
      treatment through dietary administration in male and female zebrafish on
      reproductive factors, such as gonadal activity, fertility, hatching rate and
      malformation in subsequent generations, were examined through the third filial
      (F3) generation. BPA treatment of initial generation (F0) not only caused
      retraction of the ovaries and testes but also lowered the survival rate and
      increased the rate of malformation of the offspring. Although the overall
      phenotypes of the surviving first filial (F1) generation offspring of treated
      fish initially appeared to be normal, we found abnormalities in their
      reproductive tissues after they matured to adulthood. Although the juveniles were
      fed a normal diet, the ovaries of 40% of the F1 generation fish remained small
      and did not develop vitellogenic oocytes. Moreover, sterile male fish appeared at
      a higher percentage (48%) than control (10%). Adverse transgenerational effects
      on the fecundity of the second filial (F2) and F3 generation fish were also
      observed. In each generation, survival rate of embryos were significantly low and
      abnormal embryos were appeared in offspring from BPA treated ancestral. These
      results demonstrate that the effects of BPA are transferred to subsequent
      generations not only through oocytes but also through sperm.

PMID- 30225384
TI  - New insights on liver carcinogenesis.

PMID- 30225383
TI  - Laparoscopic distal pancreatectomy: better than open?
AB  - Distal pancreatectomy is well suited to the laparoscopic approach. Laparoscopic
      distal pancreatectomy (LDP) provides the same postoperative recovery advantages
      reputed to minimal access surgery. However, there have been fears as to the
      safety of LDP in terms of life-threatening intra-operative events and post
      operative complications, adequate carcinological outcomes as compared to
      traditional (open) distal pancreatectomy (ODP) when performed for cancer, as well
      as to whether the laparoscopic approach is well adapted to the variety of
      diseases that may affect the pancreas (ranging from trauma to benign or malignant
      disease) and whether the minimal access approach is well adapted to perform
      pancreatic surgery safely in the obese, the elderly or the frail. In this review
      of the literature, we sought to determine whether LDP was as safe, provided the
      same oncological outcomes and was applicable to all diseases involving the body
      and tail of the pancreas, and to particular patient characteristics, compared to
      the traditional open approach. Last we looked at cost issues. We concluded that
      this review of the literature allowed to state that laparoscopic distal
      pancreatectomy is feasible and safe for a wide range of diseases, both benign and
      malignant. Morbidity, mortality, and probably, also, carcinological outcomes are
      comparable to open surgery. The overall costs are similar but the advantages of
      minimal access surgery make it the preferred approach, once the surgical
      expertise is acquired and present.

PMID- 30225385
TI  - Left hepatectomy in a patient with a Fontan circulation.
AB  - Patients with a Fontan circulation face the long term risk of cardiac cirrhosis
      and the subsequent development of hepatocellular carcinoma (HCC). A hepatectomy
      operation imposes significant risk on such patients as the Fontan circulation can
      be severely compromised. Here we present a 24-year-old woman post-Fontan
      operation who successfully underwent a left hepatectomy, and discuss the
      anaesthetic and surgical management.

PMID- 30225386
TI  - Pharmaconutrition administration on outcomes of elective oncological surgery for
      gastrointestinal malignancies: is timing everything?-a review of published meta
      analyses until the end of 2016.
AB  - The last 25 years have seen an increasing number of publications attesting the
      benefits of pharmaconutrition in the management of patients undergoing elective
      oncological gastrointestinal surgery. A number of randomized controlled trials
      and meta-analyses suggest the use of pharmaconutrition in this group of patients
      produces superior outcomes to standard nutritional formulations in terms of
      postoperative infective complications, anastomotic breakdown and length of
      hospital stay. The use of pharmaconutrition products, therefore, has gained
      increasing acceptance for use in elective gastrointestinal oncological surgical
      populations and been incorporated into practice guidelines. However, there
      remains doubts as to the robustness of such data supporting these recommendation.
      This is because studies reporting improved outcomes with pharmaconutrition (I)
      frequently compare this intervention with non-equivalent control groups; (II) do
      not report on the actual nutritional provision received by study participants;
      (III) overlook the potential impact of industry funding on research conducted and
      (IV) do not adopt a multi-disciplinary approach to the research undertaken. For
      these reasons, a critical re-appraisal of the use and recommendations of
      pharmaconutrition in this group of patients is urgently warranted to resolve some
      of the above mentioned issues. The aim of this review was to analyse meta
      analyses published until the end of 2016 in this area to highlight the strengths
      and weakness of the present research and prioritize certain areas which will
      benefit from future research.

PMID- 30225387
TI  - Current treatment strategies in pediatric gastrointestinal stromal cell tumor.
AB  - Gastrointestinal stromal tumors (GIST) are exceedingly rare tumors in the
      pediatric population. As a result, many clinicians either may never see this
      diagnosis or will encounter it only a few times throughout their careers.
      Additionally, the more we discover about this disease, it becomes evident that it
      represents a distinct clinical entity from adult GIST. Many of the treatments and
      strategies used to combat the adult tumor are either ineffective or may be
      harmful to the pediatric population with this disease. The unique tumor biology
      found in pediatric GIST necessitates unique approaches and treatment strategies
      in order to achieve the best clinical outcome. This review aims to discuss the
      most recent data available on the different therapeutic modalities utilized in
      cases of Pediatric GIST.

PMID- 30225388
TI  - Pediatric gastrointestinal stromal tumors-a review of diagnostic modalities.
AB  - Gastrointestinal stromal tumors are exceedingly rare tumors in the pediatric
      population, as a result many clinicians either may never see this diagnosis or
      will encounter it only a few times throughout their careers. It is imperative in
      the pediatric population to follow appropriate steps to ensure a swift diagnosis
      and referral to specialized centers that are equipped with the multidisciplinary
      teams accustomed to treating rare diseases. This review aims to discuss the most
      recent data available on the diagnostic modalities utilized in cases of suspected
      Pediatric GIST.

PMID- 30225389
TI  - Revisiting the prognostic relevance of muscle mass among non-metastatic
      colorectal cancer.

PMID- 30225390
TI  - A systematic review and meta-analysis of treatment for hepatorenal syndrome with
      traditional Chinese medicine.
AB  - Background: Hepatorenal syndrome (HRS) is a life-threatening complication of end
      stage liver diseases. It has been reported that traditional Chinese medicine
      (TCM) may improve liver function, delay disease progression, alleviate symptoms,
      and improve quality of life in HRS patients. The study aims to systematically
      review the efficacy of TCM for the treatment of HRS. Methods: Publications were
      searched electronically from China National Knowledge Infrastructure (CNKI),
      Wanfang, VIP, PubMed, and EMBASE databases. Odds ratio (OR) and standardized mean
      difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity
      was assessed. The Cochrane Collaboration's tool was used to assess the risk of
      bias. Results: Fourteen randomized controlled trials involving 788 patients with
      HRS were included. Random generation sequence was reported in only two studies.
      Blinding was not used in any study. Compared to conventional treatment without
      TCM, TCM led to a significant survival benefit during hospitalization (OR: 0.18;
      95% CI: 0.08-0.39; P<0.0001), a significantly higher complete response (OR: 3.20;
      95% CI: 2.06-4.97; P<0.00001), and a significantly lower no response (OR: 0.20;
      95% CI: 0.14-0.30; P<0.00001). Partial response was not significantly different
      between the two groups (OR: 1.39; 95% CI: 0.90-2.15; P=0.14). Regardless of TCM,
      blood urea nitrogen and abdominal circumference were significantly decreased, and
      urine volume was significantly increased after treatment. Compared to
      conventional treatment without TCM, TCM led to a significantly lower serum
      creatinine, blood urea nitrogen, bilirubin, plasma ammonia, and abdominal
      circumference and significantly higher urine volume after treatment. There was
      significant heterogeneity. Conclusions: TCM might have a better survival and a
      higher complete response in patients with HRS. However, the quality of published
      studies was unsatisfactory.

PMID- 30225392
TI  - A feasibility study prior to an international multicentre paediatric study to
      assess pharmacokinetic/pharmacodynamic sampling and sample preparation
      procedures, logistics and bioanalysis.
AB  - Background: Variability in pre-analytical procedures such as blood sampling,
      sample preparation and transport can substantially influence bioanalytical
      results and subsequently impair reliability of data gathered during clinical
      trials. Especially in vulnerable populations, all efforts should be made to
      facilitate high-quality data extraction excluding unnecessary or repeated
      intervention. Methods: The EU-funded LENA project (Labeling of Enalapril from
      Neonates up to Adolescents) included a feasibility study in its preparatory
      procedures prior to first-in-child studies. Derived from a regular study visit,
      it encompassed all procedures, from sampling of two study-specific drugs and four
      sensitive humoral parameters to bioanalysis, to evaluate the quality of obtained
      samples and applicability of logistical and bioanalytical procedures. Drug
      administration to healthy adults was circumvented by pre-spiking the blood
      collection tubes with a drug solution. Five clinical sites were evaluated.
      Results: Clinical teams' preparedness and applicability of required sampling
      procedures was investigated in 18 volunteers, on-site. 97% of collected
      pharmacokinetic (PK) samples and 93% of samples for humoral parameters were
      obtained eligibly. Results met expectations, though one team had to be re-trained
      and performed a re-run. Planned procedures for sampling, sample preparation,
      transport and analysis were found to be suitable for being applied within
      paediatric trials. Conclusion: The concept of the presented feasibility study
      that simultaneously assesses PK/PD sampling, sample preparation, logistics and
      bioanalysis proved to be a promising tool for trial preparation. It revealed
      improperly installed processes and bottlenecks that required adjustments prior to
      start of recruitment. It facilitated high-quality conduct from the first moment
      of paediatric pivotal studies.

PMID- 30225391
TI  - Treatment of trauma related anger in operation enduring freedom, operation Iraqi
      freedom, and operation New Dawn veterans: Rationale and study protocol.
AB  - Background: Problems with anger and aggression are highly prevalent in Veterans
      of multiple war eras, including the most recent conflicts in Afghanistan
      (Operation Enduring Freedom; OEF) and Iraq (Operation Iraqi Freedom; OIF). The
      consequences of these problems, such as increased rates of divorce, domestic
      violence, occupational instability, arrests and incarceration, are often
      devastating. Despite the seriousness of these problems, relatively little is
      known about effective treatments for anger in Veterans. Method and design: This
      paper describes the rationale and study protocol of a randomized controlled trial
      comparing an adapted cognitive behavioral intervention (CBI) with an active
      control condition (supportive intervention, SI) for the treatment of anger
      problems in OEF/OIF Veterans. The sample includes 92 OEF/OIF Veterans, randomized
      to CBI or SI. Both treatments include 12 weekly, 75-min individual sessions.
      Participants are assessed at baseline, after sessions 4 and 8, at post-treatment,
      and at 3 and 6 months post-treatment. Primary outcomes are reduction in anger and
      aggression; secondary outcomes are improved functioning and quality of life. We
      hypothesize that CBI will be associated with significantly more improvement than
      SI on primary and secondary measures. Discussion: Findings from this study will
      help to address the gap in evidence for effective treatments for anger in
      Veterans. The use of an active control condition will provide a stringent test of
      the effects of CBI beyond that of common factors of psychotherapy such as
      therapeutic relationship, mobilization of hope, and support. Findings have the
      potential to improve treatment outcomes for Veterans struggling with post
      deployment anger problems.

PMID- 30225393
TI  - Overall success rate of a safe and efficacious drug: Results using six phase 1
      designs, each followed by standard phase 2 and 3 designs.
AB  - To evaluate the overall success rate of a new drug, phase 1, 2, and 3 trials were
      simulated using eight toxicity and two non-decreasing efficacy profiles. Six
      phase 1 designs including the standard 3 + 3, CCD, BOIN, mTPI, mTPI-2, and CRM
      were considered with standard phase 2 and 3 designs. Based on our results, phase
      1 design recommendations are provided when data informing the general shape of
      the dose-toxicity curve exist. If a large jump in toxicity between dose levels is
      expected, the standard 3 + 3 design is recommended; it more often recognized when
      the MTD was exceeded and had the highest overall success rates. If gradually
      increasing toxicity is expected, a nonstandard design other than the CRM is
      recommended. Nonstandard designs were more aggressive in dosing and MTD
      estimation than the standard 3 + 3 and had higher overall success rates, but the
      CRM was too aggressive and most frequently overestimated the true MTD. If fairly
      constant, safe toxicity is expected across dose levels, the BOIN or CRM designs
      are recommended; they escalated to the highest dose most frequently with superior
      overall success rates. Without data informing the shape of the dose-toxicity
      curve, nonstandard phase 1 designs with a modified excessive toxicity rule more
      easily eliminating unsafe dose levels are recommended. With this modification,
      MTD overestimation error decreased and overall success rates were similar or
      higher with nonstandard designs. Among nonstandard designs, the modified CCD and
      BOIN perform well and are as transparent and simple to implement as the standard
      3 + 3 design.

PMID- 30225395
TI  - Mayo Clinic Proceedings: Having a Family at Age 92!

PMID- 30225396
TI  - The Challenging Conundrum of Diagnosing and Managing Clostridium difficile
      Infection.

PMID- 30225394
TI  - Resting-state functional brain connectivity best predicts the personality
      dimension of openness to experience.
AB  - Personality neuroscience aims to find associations between brain measures and
      personality traits. Findings to date have been severely limited by a number of
      factors, including small sample size and omission of out-of-sample prediction. We
      capitalized on the recent availability of a large database, together with the
      emergence of specific criteria for best practices in neuroimaging studies of
      individual differences. We analyzed resting-state functional magnetic resonance
      imaging data from 884 young healthy adults in the Human Connectome Project (HCP)
      database. We attempted to predict personality traits from the "Big Five", as
      assessed with the NEO-FFI test, using individual functional connectivity
      matrices. After regressing out potential confounds (such as age, sex, handedness
      and fluid intelligence), we used a cross-validated framework, together with test
      retest replication (across two sessions of resting-state fMRI for each subject),
      to quantify how well the neuroimaging data could predict each of the five
      personality factors. We tested three different (published) denoising strategies
      for the fMRI data, two inter-subject alignment and brain parcellation schemes,
      and three different linear models for prediction. As measurement noise is known
      to moderate statistical relationships, we performed final prediction analyses
      using average connectivity across both imaging sessions (1 h of data), with the
      analysis pipeline that yielded the highest predictability overall. Across all
      results (test/retest; 3 denoising strategies; 2 alignment schemes; 3 models),
      Openness to experience emerged as the only reliably predicted personality factor.
      Using the full hour of resting-state data and the best pipeline, we could predict
      Openness to experience (NEOFAC_O: r=0.24, R2=0.024) almost as well as we could
      predict the score on a 24-item intelligence test (PMAT24_A_CR: r=0.26, R2=0.044).
      Other factors (Extraversion, Neuroticism, Agreeableness and Conscientiousness)
      yielded weaker predictions across results that were not statistically significant
      under permutation testing. We also derived two superordinate personality factors
      ("alpha" and "beta") from a principal components analysis of the NEO-FFI factor
      scores, thereby reducing noise and enhancing the precision of these measures of
      personality. We could account for 5% of the variance in the beta superordinate
      factor (r=0.27, R2=0.050), which loads highly on Openness to experience. We
      conclude with a discussion of the potential for predicting personality from
      neuroimaging data and make specific recommendations for the field.

PMID- 30225397
TI  - Practical Strategies for Assessing Patient Physical Activity Levels in Primary
      Care.

PMID- 30225398
TI  - Nonexercise Estimated Cardiorespiratory Fitness and Mortality Due to All Causes
      and Cardiovascular Disease: The NHANES III Study.
AB  - Objective: To investigate associations of estimated cardiorespiratory fitness
      (eCRF) and all-cause and cardiovascular disease (CVD) mortality in a
      representative US population. Participants and Methods: A total of 12,834
      participants, aged 20 to 86 years at baseline, were included in the Third
      National Health and Nutrition Examination Survey. They were followed up from
      October 18, 1988, through December 31, 2011, for all-cause and CVD death.
      Cardiorespiratory fitness was estimated from a nonexercise algorithm and further
      grouped into tertiles. Cox proportional hazards models were used to calculate
      hazard ratios (HRs) and 95% CIs. Results: A total of 3439 deaths (999 due to CVD)
      occurred during median follow-up of 19.2 years. After adjusting for
      race/ethnicity, education, age, hypertension, diabetes, hypercholesterolemia,
      baseline CVD, and cancer status, each metabolic equivalent increase of eCRF was
      associated with an 18% (range, 15%-21%) lower risk of all-cause mortality and a
      19% (range, 15%-24%) lower risk of CVD mortality in men and a 24% (range, 20%
      28%) lower risk of all-cause mortality and a 24% (18%-30%) lower risk of CVD
      mortality in women. Compared with the lower eCRF group, the HRs (95% CIs) of the
      middle and upper groups were 0.72 (0.61-0.85) and 0.56 (0.47-0.67) for all-cause
      mortality and 0.76 (0.57-1.01) and 0.48 (0.34-0.66) for CVD mortality in men; and
      0.80 (0.66-0.97) and 0.49 (0.40-0.60) for all-cause mortality and 0.84 (0.60
      1.17) and 0.46 (0.33-0.66) for CVD mortality in women (trend P<.001 for all).
      Conclusion: High eCRF was associated with lower risk of all-cause and CVD
      mortality in a national representative population. The eCRF method has great
      potential for initial clinical risk stratification and mortality prediction.

PMID- 30225399
TI  - National Trends in the Incidence, Management, and Outcomes of Heart Failure
      Complications in Patients Hospitalized for ST-Segment Elevation Myocardial
      Infarction.
AB  - Objective: To analyze contemporary trends in the incidence, management, and
      clinical outcomes of heart failure (HF) complications in patients hospitalized
      for ST-segment elevation myocardial infarction (STEMI) in the United States.
      Patients and Methods: Using the 2003 through 2010 Nationwide Inpatient Sample
      databases, all patients with STEMI who were 18 years and older with acute HF were
      identified. Overall trends in the incidence of HF, coronary intervention, and in
      hospital mortality were analyzed. Results: Of 1,990,002 hospitalizations with a
      primary diagnosis of STEMI, 471,525 (23.7%) had HF complication (decreasing from
      25.4% [95% CI, 25.3%-25.6%] in 2003 to 20.7% [95% CI, 20.5%-20.8%]) in 2010 (P
      trend<.001). The incidence of cardiogenic shock in patients with HF-complicated
      STEMI increased from 13.9% (95% CI, 13.6%-14.1%) to 22.6% (95% CI, 22.2%-23.0%)
      during this period (P trend<.001). From 2003 through 2010, the use of diagnostic
      coronary angiography and percutaneous coronary intervention increased in patients
      with HF-complicated STEMI from 44.3% to 62.1% and from 25.0% to 48.1%,
      respectively. In-hospital mortality decreased significantly in patients with HF
      complicated STEMI (from 18.1% to 15.1%) and in subgroups of those with (from
      42.4% to 29.9%) and without (from 14.1% to 10.8%) cardiogenic shock (all P
      trend<.001). The adjusted odds ratio (AOR) (per year) of death was 0.992 (95% CI,
      0.988-0.997; P<.001), which changed significantly after additional adjustment for
      coronary intervention (AOR [per year], 1.012; 95% CI, 1.008-1.017; P<.001).
      Conclusion: The incidence and in-hospital mortality of HF-complicated STEMI has
      decreased significantly during recent times along with increased use of
      percutaneous coronary intervention and diagnostic coronary angiography.

PMID- 30225400
TI  - Acute Alcoholic Hepatitis: Natural History and Predictors of Mortality Using a
      Multicenter Prospective Study.
AB  - Objective: To examine the natural history of acute alcoholic hepatitis (AH) and
      identify predictors of mortality for AH using data from a prospective multicenter
      observational study. Participants and Methods: We analyzed data from 164 patients
      with AH and 131 heavy-drinking controls with no liver disease. Participants
      underwent clinical/laboratory assessment at baseline and 6 and 12 months after
      enrollment. Multivariable analyses were conducted to identify variables
      associated with mortality and examine the association between coffee drinking and
      risk of AH. Results: Thirty-six patients with AH died during follow-up, with
      estimated 30-day, 90-day, 180-day, and 1-year survival of 0.91 (95% CI, 0.87
      0.96), 0.85 (95% CI, 0.80-0.91), 0.80 (95% CI, 0.74-0.87), and 0.75 (95% CI, 0.68
      0.83), respectively. In the multivariable analysis, higher serum bilirubin level
      (hazard ratio [HR]=1.059; 95% CI, 1.022-1.089), lower hemoglobin level (HR=1.263;
      95% CI, 1.012-1.575), and lower platelet count (HR=1.006; 95% CI, 1.001-1.012)
      were independently associated with mortality in AH. Compared with controls, fewer
      patients with AH regularly consumed coffee (20% vs 44%; P<.001), and this
      association between regular coffee drinking and lower risk of AH persisted after
      controlling for relevant covariates (odds ratio=0.26; 95% CI, 0.15-0.46). Time
      dependent receiver operating characteristic curve analysis revealed that Model
      for End-Stage Liver Disease; Maddrey Discriminant Function; age, serum bilirubin,
      international normalized ratio, and serum creatinine; and Child-Pugh scores all
      provided similar discrimination performance at 30 days (area under the curve=0.73
      0.77). Conclusion: Alcoholic hepatitis remains highly fatal, with 1-year
      mortality of 25%. Regular coffee consumption was associated with lower risk of AH
      in heavy drinkers.

PMID- 30225401
TI  - Experience and Outcomes at a Specialized Clostridium difficile Clinical Practice.
AB  - Objective: To report our experience with and outcomes among patients referred to
      a specialized Clostridium difficile clinical practice. Patients and Methods: We
      retrospectively identified consecutive patients referred for Clostridium
      difficile infection (CDI) management from January 1, 2013, through May 30, 2015.
      Data were collected for demographic characteristics, CDI history, final
      diagnoses, and management. Results: Overall, 211 patients (median age, 65 years;
      66.4% women) were included. The most common indications for referral were
      recurrent CDI in 199 patients (94.3%), first CDI episode in 5 patients (2.4%),
      and chronic diarrhea in 7 patients (3.3%). After evaluation, the diagnoses were
      recurrent CDI in 127 patients (60.2%), resolved CDI in 36 patients (17.1%), first
      episode CDI in 5 patients (2.4%), and non-CDI in 43 patients (20.4%). The most
      common non-CDI diagnoses were postinfection irritable bowel syndrome (PI-IBS) in
      32 patients (15.2% overall), inflammatory bowel disease (n=3), small intestinal
      bacterial overgrowth (n=2), microscopic colitis (n=1), and asymptomatic C
      difficile colonization (n=2). Two patients had diabetic gastroparesis and food
      intolerances, and 1 had chronic constipation with overflow diarrhea. Of 127
      patients with recurrent CDI, 30 (23.6%) received antibiotics; of these 30, 12 had
      antibiotic treatment failure and received fecal microbiota transplantation (FMT)
      for recurrent CDI. Among 97 patients (76.4%) who underwent FMT, 85 (87.6%) were
      cured after the first FMT, 5 were cured after the second FMT, and 7 were treated
      with antibiotics for FMT failure, with resolution of symptoms. Conclusion: A
      substantial proportion of patients referred for CDI subsequently received
      alternative diagnoses; PI-IBS was the most common. Patients being referred for
      recurrent CDI should be evaluated carefully for alternative diagnoses.

PMID- 30225402
TI  - Normalization of Testosterone Levels After Testosterone Replacement Therapy Is
      Not Associated With Reduced Myocardial Infarction in Smokers.
AB  - Objective: To examine the effect of cigarette smoking (CS) status and total
      testosterone (TT) levels after testosterone replacement therapy (TRT) on all
      cause mortality, myocardial infarction (MI), and stroke in male smokers and
      nonsmokers without history of MI and stroke. Participants and Methods: Data from
      18,055 males with known CS status and low TT levels who received TRT at the
      Veterans Health Administration between December 1, 1999, and May 31, 2014, were
      grouped into (1) current smokers with normalized TT, (2) current smokers with
      nonnormalized TT, (3) nonsmokers with normalized TT, and (4) nonsmokers with
      nonnormalized TT. Combined effect of CS status and TT level normalization after
      TRT on all-cause mortality, MI, and stroke was compared using propensity score
      weighted Cox proportional hazard models. Results: Normalization of serum TT
      levels in nonsmokers was associated with a significant decrease in all-cause
      mortality (hazard ratio [HR]=0.526; 95% CI, 0.477-0.581; P<.001) and MI
      (HR=0.717; 95% CI, 0.522-0.986; P<.001). Among current smokers, normalization of
      serum TT levels was associated with a significant decrease in only all-cause
      mortality (HR=0.563; 95% CI, 0.488-0.649; P<.001) without benefit in MI
      (HR=1.096; 95% CI, 0.698-1.720; P=.69). Importantly, compared with nonsmokers
      with normalized TT, all-cause mortality (HR=1.242; 95% CI, 1.104-1.396; P<.001),
      MI (HR=1.706; 95% CI, 1.242-2.342; P=.001), and stroke (HR=1.590; 95% CI, 1.013
      2.495; P=.04) were significantly higher in current smokers with normalized TT.
      Conclusion: We conclude that active CS may negate the protective effect of
      testosterone level normalization on all-cause mortality and MI after TRT.

PMID- 30225403
TI  - Combined Association of Cardiorespiratory Fitness and Body Fatness With
      Cardiometabolic Risk Factors in Older Norwegian Adults: The Generation 100 Study.
AB  - Objective: To investigate the independent and combined associations of fitness
      and fatness with cardiometabolic risk factors in older Norwegian women and men.
      Patients and Methods: We conducted a cross-sectional study of 505 women and 417
      men aged 70 to 77 years enrolled in the Generation 100 study in Norway. Fitness
      was assessed as peak oxygen uptake and fatness as high body mass index (BMI; >=25
      kg/m2), waist circumference (WC) of 88 cm or greater for women and 102 cm or
      greater for men, and percent body fat (%BF) of 35% or greater and 25% or greater
      for women and men, respectively. High cardiometabolic risk was defined as the
      presence of 2 or more of the following risk factors: elevated triglyceride level,
      reduced high-density lipoprotein cholesterol concentration, elevated blood
      pressure, and elevated fasting glucose level or pharmacological treatment of
      these conditions. Results: Receiver operating characteristic curve analyses
      identified fitness levels of less than 25.7 and less than 30.7 mL/kg per minute
      in women and men, respectively, as critical thresholds for having high
      cardiometabolic risk. Individuals with levels below these thresholds had an
      adjusted odds ratio of 2.77 (95% CI, 2.09-3.66) for having high cardiometabolic
      risk, while high BMI, WC, and %BF had odds ratios (95% CIs) of 3.58 (2.69-4.77),
      3.06 (2.29-4.10), and 3.26 (2.47-4.30), respectively. In our combined analyses,
      being lean did not attenuate the cardiometabolic risk associated with low
      fitness, and combinations of low fitness and/or high BMI, WC, or %BF cumulatively
      increased cardiometabolic risk. Conclusion: Low fitness and indication of fatness
      were independently and cumulatively associated with poor cardiometabolic health.
      Our results emphasize the importance of including both physical fitness and body
      fatness in the assessment of cardiometabolic risk and health promotion efforts in
      older adults.

PMID- 30225404
TI  - Pretravel Health Preparation of International Travelers: Results From the Boston
      Area Travel Medicine Network.
AB  - Objective: To inform future interventions for advising travelers. Patients and
      Methods: We prospectively collected data on travelers seen at the Boston Area
      Travel Medicine Network, a Boston area research collaboration of 5 travel
      medicine clinics. Data from 15,440 travelers were collected from March 1, 2008,
      through July 31, 2010. We compared traveler and trip characteristics and
      differences in demographic characteristics and travel plans across the 5 clinics,
      including an analysis of pretravel preparations for certain high-risk
      destinations. Results: More than half of the 15,440 travelers were female (8730
      [56.5]), and 72.4% (10,528 of 14,545) were white; the median age was 34 years,
      and 29.4% of travelers (3077 of 10,483) were seen less than 2 weeks before their
      departure date. Substantial variation in racial background, purpose of travel,
      and destination risk existed across the 5 clinics. For example, the proportion of
      travelers visiting friends and relatives ranged from 7.6% (184 of 2436) to 39.0%
      (1029 of 2639) (18.7% [2876 of 15,360] overall), and the percentage of travelers
      to areas with malaria risk ranged from 23.7% (333 of 1403) to 52.0% (1306 of
      2512). Although most clinics were likely to have prescribed certain vaccines for
      high-risk destinations (eg, yellow fever for Ghana travel), there was wide
      variability in influenza vaccine use for China travel. Conclusion: Substantial
      differences in clinic populations can occur within a single metropolitan area,
      highlighting why individual physicians and travel clinics need to understand the
      specific needs of the travelers they serve in addition to general travel
      medicine.

PMID- 30225405
TI  - Effect of Antimicrobial Stewardship Program Guidance on the Management of
      Uncomplicated Skin and Soft Tissue Infections in Hospitalized Adults.
AB  - Objective: To assess the effect of an antimicrobial stewardship program (ASP)
      bundled initiative on the appropriate use of antibiotics for uncomplicated skin
      and soft tissue infections (uSSTIs) at 2 academic medical centers in Pittsburgh,
      Pennsylvania. Patients and Methods: A retrospective preintervention and
      postintervention study was conducted to compare management of patients admitted
      with uSSTIs before and after the implementation of the bundled initiative. The
      preintervention period was from August 1, 2014, through March 31, 2015, and the
      postintervention period was from August 1, 2015, through March 31, 2016. Results:
      A total of 160 patients were included in the preintervention cohort, and 163 were
      included in the postintervention cohort. Compared with the preintervention group,
      the mean duration of therapy decreased (12.5 days vs 8.8 days; P<.001) and an
      appropriate duration of less than 10 days increased in more patients (20.6% [33
      of 160] vs 68.7% [112 of 163]; P<.001) in the postintervention period. Fewer
      patients were exposed to antimicrobials with extended gram-negative (44.4% [71 of
      160] vs 9.2% [15 of 163]; P<.001), anaerobic (39.4% [63 of 160] vs 9.8% [16 of
      163]; P<.001), and antipseudomonal (16.3% [26 of 160] vs 1.8% [3 of 163]; P<.001)
      coverage. The mean length of stay decreased from 3.6 to 2.2 days (P<.001) without
      an increase in 30-day readmissions (6.3% [10 of 160] vs 4.9% [8 of 163]; P=.64).
      The ASP made recommendations for 125 patients, and 96% were accepted. Conclusion:
      Implementation of an ASP-bundled approach aimed at optimizing antibiotic therapy
      in the management of uSSTIs led to shorter durations of narrow-spectrum therapy
      as well as shorter hospital length of stay without adversely affecting hospital
      readmissions.

PMID- 30225406
TI  - Automated Diabetes Case Identification Using Electronic Health Record Data at a
      Tertiary Care Facility.
AB  - Objective: To develop and validate a phenotyping algorithm for the identification
      of patients with type 1 and type 2 diabetes mellitus (DM) preoperatively using
      routinely available clinical data from electronic health records. Patients and
      Methods: We used first-order logic rules (if-then-else rules) to imply the
      presence or absence of DM types 1 and 2. The "if" clause of each rule is a
      conjunction of logical and, or predicates that provides evidence toward or
      against the presence of DM. The rule includes International Classification of
      Diseases, Ninth Revision, Clinical Modification diagnostic codes, outpatient
      prescription information, laboratory values, and positive annotation of DM in
      patients' clinical notes. This study was conducted from March 2, 2015, through
      February 10, 2016. The performance of our rule-based approach and similar
      approaches proposed by other institutions was evaluated with a reference standard
      created by an expert reviewer and implemented for routine clinical care at an
      academic medical center. Results: A total of 4208 surgical patients (mean age, 52
      years; males, 48%) were analyzed to develop the phenotyping algorithm. Expert
      review identified 685 patients (16.28% of the full cohort) as having DM. Our
      proposed method identified 684 patients (16.25%) as having DM. The algorithm
      performed well-99.70% sensitivity, 99.97% specificity-and compared favorably with
      previous approaches. Conclusion: Among patients undergoing surgery, determination
      of DM can be made with high accuracy using simple, computationally efficient
      rules. Knowledge of patients' DM status before surgery may alter physicians' care
      plan and reduce postsurgical complications. Nevertheless, future efforts are
      necessary to determine the effect of first-order logic rules on clinical
      processes and patient outcomes.

PMID- 30225407
TI  - A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation
      Sequencing-Based Circulating Tumor DNA Profiling Exhibits Excellent Response to
      Crizotinib.
AB  - The ALK gene fusion has been identified as a new driver gene in non-small cell
      lung cancer (NSCLC). It includes the EML4-ALK rearrangement as a recurring event
      that renders the tumor sensitive to ALK tyrosine kinase inhibitor crizotinib. In
      addition, several other fusion partners to ALK kinase domain (eg, TFG, KLC1, and
      KIF5B) have been identified in NSCLC. However, clinical data relevant to response
      in lung cancer harboring these rare ALK translocations are not fully available. A
      nonsmoking Chinese male originally diagnosed with "stage Ib lung adenocarcinoma"
      showed metastases in regional lymph nodes, pleura, and bone 1 year after surgery.
      The patient refused invasive tissue biopsy, and chemotherapy was administrated,
      which failed as a first- and second-line treatment. We then identified a rare
      fusion gene of ALK and Striatin (STRN) using next-generation sequencing (NGS)
      based circulating tumor DNA (ctDNA) analysis. The NGS of the patient's originally
      paraffin-embedded surgical tumor samples also indicated the fusion. Reverse
      transcription-polymerase chain reaction and Sanger sequencing further confirmed
      the results. The STRN-ALK involves the fusion of exon 3 of STRN retaining a
      coiled-coil domain to exon 20 of ALK containing a kinase domain. The patient was
      treated with crizotinib and showed excellent clinical, radiographic, and
      molecular response. Repetitive dynamic ctDNA analysis revealed that the fraction
      of molecular alterations in plasma was closely associated with response to
      crizotinib treatment. This is the first clinical evidence involving advanced
      NSCLC due to a rare STRN-ALK fusion and has been effectively treated with
      crizotinib.

PMID- 30225408
TI  - Science of Health Care Delivery: An Innovation in Undergraduate Medical Education
      to Meet Society's Needs.
AB  - The purpose of this special article is to describe a new, 4-year Science of
      Health Care Delivery curriculum at Mayo Clinic School of Medicine, including
      curricular content and structure, methods for instruction, partnership with
      Arizona State University, and implementation challenges. This curriculum is
      intended to ensure that graduating medical students enter residency prepared to
      train and eventually practice within person-centered, community- and population
      oriented, science-driven, collaborative care teams delivering high-value care. A
      Science of Health Care Delivery curriculum in undergraduate medical education is
      necessary to successfully prepare physicians so as to ensure the best clinical
      outcomes and patient experience of care, at the lowest cost.

PMID- 30225410
TI  - Development of an Interdisciplinary Pediatric Pain Rehabilitation Program: The
      First 1000 Consecutive Patients.
AB  - Objective: To describe the development of a clinically and financially successful
      interdisciplinary pediatric pain rehabilitation program at a large tertiary
      academic medical center and present demographic and clinical information on the
      first 1000 patients. Patients and Methods: All patients who were consecutively
      admitted to this program between October 1, 2008, and March 31, 2015 were
      included in this review. The patients ranged in age from 9 to 24 years. The
      program is a 3-week, hospital-based outpatient treatment program that requires
      substantial parental involvement. At admission and discharge, patients completed
      the Center for Epidemiologic Studies of Depression Scale for Children, the
      Functional Disability Inventory, and the Pain Catastrophizing Scale for Children.
      Opioid use was also assessed. Results: At admission, patients reported
      substantial pain-associated disability and depressive symptoms; they had elevated
      pain catastrophizing scores, and 16% were taking opioids. Primary sites/types of
      pain included head, abdomen, and generalized. Functional disability scores
      decreased significantly, from 27 to 9 after the program (P<.001). Depression
      scale scores improved from 27 to 14 (P<.001). Pain catastrophizing scores
      decreased significantly, from 26 to 14 (P<.001), at discharge from the program.
      All but 4 patients successfully tapered off of all opioid use by the conclusion
      of the program. Conclusion: Participation in a multidisciplinary pediatric pain
      rehabilitation program can be successful, with significant decreases in
      disability, depression symptoms, and pain catastrophizing, as well as
      discontinuation of opioid use.

PMID- 30225409
TI  - A Multifaceted Organizational Physician Assessment Program: Validity Evidence and
      Implications for the Use of Performance Data.
AB  - Objective: To provide validity evidence for a multifaceted organizational program
      for assessing physician performance and evaluate the practical and psychometric
      consequences of 2 approaches to scoring (mean vs top box scores). Participants
      and Methods: Participants included physicians with a predominantly outpatient
      practice in general internal medicine (n=95), neurology (n=99), and psychiatry
      (n=39) at Mayo Clinic from January 1, 2013, through December 31, 2014. Study
      measures included hire year, patient complaint and compliment rates, note-signing
      timeliness, cost per episode of care, and Likert-scaled surveys from patients,
      learners, and colleagues (scored using mean ratings and top box percentages).
      Results: Physicians had a mean +/- SD of 0.32+/-1.78 complaints and 0.12+/-0.76
      compliments per 100 outpatient visits. Most notes were signed on time (mean +/-
      SD, 96%+/-6.6%). Mean +/- SD cost was 0.56+/-0.59 SDs above the institutional
      average. Mean +/- SD scores were 3.77+/-0.25 on 4-point and 4.06+/-0.31 to 4.94+/
      0.08 on 5-point Likert-scaled surveys. Mean +/- SD top box scores ranged from
      18.6%+/-16.8% to 90.7%+/-10.5%. Learner survey scores were positively associated
      with patient survey scores (r=0.26; P=.003) and negatively associated with years
      in practice (r=-0.20; P=.02). Conclusion: This study provides validity evidence
      for 7 assessments commonly used by medical centers to measure physician
      performance and reports that top box scores amplify differences among high
      performing physicians. These findings inform the most appropriate uses of
      physician performance data and provide practical guidance to organizations
      seeking to implement similar assessment programs or use existing performance data
      in more meaningful ways.

PMID- 30225411
TI  - Influence of Referral to a Combined Diabetology and Nephrology Clinic on Renal
      Functional Trends and Metabolic Parameters in Adults With Diabetic Kidney
      Disease.
AB  - Objective: To examine the impact of a diabetes renal clinic (DRC) on renal
      functional and metabolic indices in adults who have diabetes mellitus (DM) and
      chronic kidney disease (CKD). Patients and Methods: All patients evaluated at a
      DRC in a single tertiary referral center from January 1, 2008, to December 31,
      2012, were identified. Serial renal and metabolic indices from January 1, 2004,
      to December 31, 2014, were recorded, and trends over time were analyzed by linear
      mixed-effects models. Results: A total of 200 patients who had DM and CKD were
      identified and subdivided into 3 categories based on presumptive CKD etiology: 43
      (21.5%) with type 1 DM (T1D) only, 127 (63.5%) with type 2 DM (T2D) only, and 30
      (15.0%) with DM and an additional CKD etiology. Average annual absolute (mL/min
      per body surface area per year) and percentage (%/year) changes, respectively, in
      Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration
      rate before vs after first DRC attendance were: -1.59 vs -3.10 (P=.31) and -1.22
      vs -9.39 (P=.06) for T1D; -5.64 vs -3.07 (P=.004) and -10.88 vs -9.94 (P=.70) for
      T2D; and -6.50 vs +0.91 (P<.001) and -13.28 vs -2.29 (P=.001) for DM with an
      additional CKD etiology. Glycemic control worsened in those who had T2D, whereas
      trends in total cholesterol levels improved in those who had T1D. Conclusion:
      After first DRC attendance, the absolute rate of estimated glomerular filtration
      rate decline remained similar for those who had T1D, but it slowed for those who
      had T2D or DM with additional CKD etiology. Thus, benefits of combined
      diabetology and nephrology consultation may vary for different diabetic
      subpopulations.

PMID- 30225412
TI  - Monoclonal Gammopathy of Undetermined Significance: Follow-up Patterns in the
      United States and Concordance With Clinical Practice Guidelines.
AB  - Objective: To determine follow-up practice patterns of US patients with
      monoclonal gammopathy of undetermined significance (MGUS) and their concordance
      with 4 clinical practice guidelines. Patients and Methods: In a retrospective
      analysis of adult patients using the OptumLabs Data Warehouse database, we
      identified those who had an incident diagnosis of MGUS from January 1, 2006,
      through December 31, 2013, no history or subsequent diagnosis of
      lymphoplasmacytic malignancy, and at least 2 years of follow-up. Results: A total
      of 11,676 patients with MGUS were included in the study. During the first 2 years
      after MGUS diagnosis, the distribution of patients by mean interval between
      visits was as follows: less than 6 months, 12.7%; every 6 to 12 months, 25.2%;
      every 13 to 24 months, 17.7%; and longer than 24 months, 44.4%. A higher
      proportion of patients were followed up at intervals of less than 13 months over
      time, from 32.7% to 41.1% (P<.001). Patients 60 years or older were more likely
      to be followed up at intervals of less than 13 months; those from the Northeast
      or younger than 50 years were more likely to be followed up at intervals longer
      than 24 months compared with their counterparts (P<.001). More than half of the
      patients 80 years or older were followed up at intervals of less than 6 months
      (12.3%), 6 to 12 months (27.8%), or 13 to 24 months (18.2%). Only approximately
      half of the patients (41.1%-58.8%) with MGUS diagnosed in 2013 were concordant
      with any of the 4 clinical guidelines. Conclusion: The MGUS follow-up practice
      patterns varied geographically and demographically and were frequently discordant
      with guideline recommendations. A large proportion of patients with limited life
      expectancy had frequent follow-up visits.

PMID- 30225413
TI  - An Assessment of the AdenoPlus Point-of-Care Test for Diagnosing Adenoviral
      Conjunctivitis and Its Effect on Antibiotic Stewardship.
AB  - Objective: To determine the sensitivity and specificity of the AdenoPlus test
      compared with real-time polymerase chain reaction (PCR) and to determine whether
      there was a reduction in antibiotic prescriptions with the use of AdenoPlus
      compared with the previous year. Patients and Methods: A total of 125 patients
      with suspected infectious conjunctivitis were accrued from June 4, 2015, through
      September 27, 2015. Forty-six participants from the prospective cohort completed
      both AdenoPlus and PCR testing. Two hundred fifty age-matched individuals were in
      the retrospective cohort. Results: There was a significant reduction in the
      percentage of patients who received an antibiotic ophthalmic prescription in the
      prospective cohort vs the retrospective cohort (32% vs 45%; chi2P=.01). AdenoPlus
      test sensitivity was 50% (5 of 10) and specificity was 92% (33 of 36) compared
      with real-time PCR testing. Conclusion: The AdenoPlus test has high specificity
      for diagnosing adenoviral conjunctivitis but lower sensitivity than has been
      previously published. These data suggest that negative AdenoPlus results should
      be confirmed by real-time PCR owing to the low overall sensitivity of AdenoPlus
      observed.

PMID- 30225414
TI  - Injection Pharyngoplasty With a Hyaluronic Acid and Dextranomer Copolymer to
      Treat Velopharyngeal Insufficiency in Adults.
AB  - Objective: To describe the treatment of adult velopharyngeal insufficiency (VPI)
      with injection of a hyaluronic acid and dextranomer copolymer (Dx/HA). Patients
      and Methods: This was a retrospective case series of 25 consecutively treated
      adults with VPI who underwent Dx/HA injection pharyngoplasty in a
      multidisciplinary clinic from January 1, 2011, to December 31, 2014. Data
      recorded included etiology of VPI, perceptual analysis of resonance, nasalance
      scores, and estimation of velopharyngeal gap characteristics on video
      nasendoscopy before and after the intervention. Statistical comparisons were made
      using a 2-tailed Wilcoxon signed rank test and the Kruskal-Wallis test. Results:
      Patients had VPI due to a neurologic etiology, due to a benign anatomic etiology,
      or acquired after treatment for a head and neck malignancy. Injections were
      performed with local anesthesia, monitored anesthesia care, or general
      anesthesia. There were statistically significant improvements in speech
      resonance, nasalance, and velopharyngeal gap size after treatment. Patients with
      neurologic or benign anatomic etiologies of their VPI had more significant
      improvement than those with VPI after treatment of malignancy. Nineteen of the 25
      patients required only 1 injection to achieve their final result. Conclusion:
      Injection pharyngoplasty with a readily available Dx/HA is an effective treatment
      for VPI that allows for titration to complete velopharyngeal closure under local
      anesthesia or light sedation. It is most effective in patients with nonmalignant
      etiologies of VPI and in those with good lateral wall motion. Complications
      experienced were postoperative neck pain and occult retropharyngeal fluid
      collection, highlighting the importance of follow-up.

PMID- 30225415
TI  - Cell-Based Therapy for Myocardial Dysfunction After Fontan Operation in
      Hypoplastic Left Heart Syndrome.
AB  - Myocardial dysfunction after Fontan palliation for univentricular congenital
      heart disease is a challenging clinical problem. The medical treatment has a
      limited impact, with cardiac transplant being the ultimate management step. Cell
      based therapies are evolving as a new treatment for heart failure. Phase 1
      clinical trials using regenerative therapeutic strategies in congenital heart
      disease are ongoing. We report the first case of autologous bone marrow-derived
      mononuclear cell administration for ventricular dysfunction, 23 years after
      Fontan operation in a patient with hypoplastic left heart syndrome. The cells
      were delivered into the coronary circulation by cardiac catheterization.
      Ventricular size decreased and several parameters reflecting ventricular function
      improved, with maximum change noted 3 months after cell delivery. Such
      regenerative therapeutic options may help in delaying and preventing cardiac
      transplant.

PMID- 30225416
TI  - Brachial Plexus Neuritis Associated With Anti-Programmed Cell Death-1 Antibodies:
      Report of 2 Cases.
AB  - Recently, guidelines have been outlined for management of immune-related adverse
      events occurring with immune checkpoint inhibitors in cancer, irrespective of
      affected organ systems. Increasingly, these complications have been recognized as
      including diverse neuromuscular presentations, such as demyelinating and axonal
      length-dependent peripheral neuropathies, vasculitic neuropathy, myasthenia
      gravis, and myopathy. We present 2 cases of brachial plexopathy developing on
      anti-programmed cell death-1 checkpoint inhibitor therapies (pembrolizumab,
      nivolumab). Both cases had stereotypic lower-trunk brachial plexus-predominant
      onsets, and other clinical features distinguishing them from Parsonage-Turner
      syndrome (ie, idiopathic plexitis). Each case responded to withholding of anti
      programmed cell death-1 therapy, along with initiation of high-dose
      methylprednisiolone therapy. However, both patients worsened when being weaned
      from corticosteroids. Discussed are the complexities in the decision to add a
      second-line immunosuppressant drug, such as infliximab, when dealing with
      neuritis attacks, for which improvement may be prolonged, given the inherent slow
      recovery seen with axonal injury. Integrated care with oncology and neurology is
      emphasized as best practice for affected patients.

PMID- 30225417
TI  - Achalasia in a Patient Undergoing Hematologic Stem Cell Transplant After Exposure
      to Tacrolimus.
AB  - Calcineurin inhibitors (CNIs) are effective agents used for prevention of graft
      vs-host disease after allogeneic hematopoietic stem cell transplant or for organ
      rejection in solid-organ transplant. However, CNIs have a wide range of adverse
      effects that may necessitate changing to another CNI or immunosuppressive agent.
      We report a case of acute myeloid leukemia in which achalasia developed after
      exposure to tacrolimus, as revealed by esophagram results. The patient's symptoms
      and signs were ameliorated after a change to cyclosporine. This case is the first
      in the literature to reveal achalasia associated with tacrolimus. Achalasia
      should be part of a differential diagnosis of upper gastrointestinal symptoms in
      patients undergoing transplant, and changing to another CNI may be a useful
      therapeutic intervention.

PMID- 30225418
TI  - A Worksite Wellness Intervention: Improving Happiness, Life Satisfaction, and
      Gratitude in Health Care Workers.
AB  - Objective: To assess the effect of a 12-week Stress Management and Resilience
      Training (SMART) program on happiness, life satisfaction, gratitude, mindfulness,
      spirituality, and stress in health care workers. Participants and Methods:
      Participants were members of an employee wellness center at an academic health
      care center. Participants were enrolled as cohorts of 12 to 18 individuals and
      received the intervention at an employee wellness center from February 19, 2013,
      to February 27, 2017. The study was designed as a prospective, nonrandomized,
      single-arm clinical trial that included a 3-month in-person SMART program
      (defined as the intervention), with an additional 3-month postintervention follow
      up period (6 months total). Outcomes were assessed at baseline (T0), end of
      intervention (T3), and after the postintervention follow-up period (T6) and
      included Subjective Happiness Survey, Satisfaction with Life Scale, Gratitude
      Scale, Mindful Attention Awareness Scale, Functional Assessment of Chronic
      Illness Therapy - Spiritual Well-Being, and Perceived Stress Scale. Results: Of
      the 110 participants who enrolled and provided consent, 98 participants (89%)
      completed the T0 and T3 assessments and 85 participants (77%) completed the T0,
      T3, and T6 assessments. On comparing the T0 and T6 responses, we observed
      statistically significant improvements (P<.001) in all the domains studied:
      subjective happiness (baseline average, 4.6; T6 average, 5.5; average difference,
      0.9; 95% CI, 0.6-1.0), life satisfaction (baseline average, 22.8; T6 average,
      27.5; average difference, 4.7; 95% CI, 3.6-5.9); gratitude (baseline average,
      35.8; T6 average, 39.3; average difference, 3.5; 95% CI, 2.6-4.5), mindfulness
      (baseline average, 3.5; T6 average, 4.2; average difference, 0.7; 95% CI, 0.6
      0.9), Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being
      (baseline average, 29.9; T6 average, 37.4; average difference, 7.5; 95% CI, 6.0
      9.2), and percentage of people reporting high stress (baseline, 97.6%; T6,
      67.1%). Similar results were observed when comparing the T0 and T3 responses.
      Conclusion: In health care workers, training in the SMART program was associated
      with statistically significant improvements in happiness, satisfaction with life,
      gratitude, mindfulness, spirituality, and stress (P<.001). Given the importance
      of stress in the workplace, larger randomized trials and broader dissemination of
      the program in health care workers is warranted.

PMID- 30225419
TI  - Family Help With Medication Management: A Predictive Marker for Early
      Readmission.
AB  - Objectives: To identify aspects of medication management that are associated with
      a greater risk of hospital readmission. Patients and Methods: We conducted a
      prospective cohort study, with a thorough medication history and reconciliation
      performed at admission and discharge. Patients 18 years or older (N=258) were
      prospectively enrolled on admission to a cardiology service at a tertiary care
      hospital from September 1, 2011, through July 31, 2012. All patients received
      their hospital and outpatient care within our institution, which minimized loss
      to follow-up. Readmission rates within 30 days and 6 months after discharge were
      recorded and used to investigate associations with specific characteristics
      related to medication regimen and management. Nominal logistic fit tests were
      used to establish associations with risk factors. Results: A higher risk of
      readmission within 30 days after discharge was seen with heart failure diagnosis
      (P=.003) and with increased severity of comorbid conditions based on Charlson
      score (P=.02). Patients whose family managed their medications entirely had a
      higher risk of readmission at 30 days (odds ratio, 2.92; 95% CI, 1.25-5.6; P=.01)
      and at 6 months (odds ratio, 3.54; 95% CI, 1.70-7.65; P<.001). These findings
      were independent of the presence of heart failure. Conclusion: Patients requiring
      family member support with medication management should be considered at
      increased risk for readmission. Increased focus on these patients at discharge
      may help decrease readmissions.

PMID- 30225420
TI  - Improving Blood Pressure Management and Disease Severity Documentation in
      Patients With Acute Intracerebral Hemorrhage.
AB  - Objective: To ensure prime blood pressure management and intracerebral hemorrhage
      (ICH) score documentation within 6 hours of arrival and/or before any
      intervention in patients admitted to Mayo Clinic Hospital with acute ICH.
      Patients and Methods: A quality improvement initiative was conducted between
      September 29, 2015, and May 30, 2017, following the Define-Measure-Analyze
      Improve-Control methodology. Our prespecified goals for the first 8 months
      postintervention were that at least 80% of patients with ICH will have systolic
      blood pressure (SBP) control as per guideline-based recommendations (SBP <=140 mm
      Hg) and at least 80% will have ICH score documented within 6 hours postadmission.
      Neurovascular stakeholders' feedback was included in the process development.
      Practice gaps and their leading causes were identified and served rational
      interventions' planning. Education and admission order-set modifications were
      chosen as intervention methods. Results: At 4 (first measurement, n=13) and 8
      months (second measurement, n=15) postintervention, 92.3% and 100% of patients
      with ICH, respectively, reached the target SBP, compared with 50% in the
      preintervention group (comparison group, n=26); 84.6% and 85.7% of the patient
      population had the ICH score documented at the first and second outcome
      measurement, respectively, compared with 42.3% in the preintervention group.
      Stakeholders reported good satisfaction with the novel applications.
      Sustainability plans and future directions were established. Conclusion:
      Effective education methods enhance the introduction of guideline-based clinical
      practices. This quality improvement project has the potential to impact patient
      outcomes, staff efficiency, and stroke centers' maintenance of certification and
      quality care recognition. This initiative warrants implementation at hospitals
      across all Mayo Clinic campuses and nationwide.

PMID- 30225421
TI  - Influence of Initial Provider on Health Care Utilization in Patients Seeking Care
      for Neck Pain.
AB  - Objective: To examine patients seeking care for neck pain to determine
      associations between the type of provider initially consulted and 1-year health
      care utilization. Patients and Methods: A retrospective cohort of 1702 patients
      (69.25% women, average age, 45.32+/-14.75 years) with a new episode of neck pain
      who consulted a primary care provider, physical therapist (PT), chiropractor
      (DC), or specialist from January 1, 2012, to June 30, 2013, was analyzed.
      Descriptive statistics were calculated for each group, and subsequent 1-year
      health care utilization of imaging, opioids, surgery, and injections was compared
      between groups. Results: Compared with initial primary care provider
      consultation, patients consulting with a DC or PT had decreased odds of being
      prescribed opioids within 1 year from the index visit (DC: adjusted odds ratio
      [aOR], 0.54; 95% CI, 0.39-0.76; PT: aOR, 0.59; 95% CI, 0.44-0.78). Patients
      consulting with a DC additionally demonstrated decreased odds of advanced imaging
      (aOR, 0.43; 95% CI, 0.15-0.76) and injections (aOR, 0.34; 95% CI, 0.19-0.56).
      Initiating care with a specialist or PT increased the odds of advanced imaging
      (specialist: aOR, 2.96; 95% CI, 2.01-4.38; PT: aOR, 1.57; 95% CI, 1.01-2.46), but
      only initiating care with a specialist increased the odds of injections (aOR,
      3.21; 95% CI, 2.31-4.47). Conclusion: Initially consulting with a
      nonpharmacological provider may decrease opioid exposure (PT and DC) over the
      next year and also decrease advanced imaging and injections (DC only). These data
      provide an initial indication of how following recent practice guidelines may
      influence health care utilization in patients with a new episode of neck pain.

PMID- 30225422
TI  - Overall Cost Comparison of Gastrointestinal Endoscopic Procedures With
      Endoscopist- or Anesthesia-Supported Sedation by Activity-Based Costing
      Techniques.
AB  - Objective: Endoscopic/colonoscopic procedures are either done with
      gastroenterologist-administered conscious sedation or with anesthesia
      administered sedation with propofol. There are potential benefits to anesthesia
      administered sedation, but the concern has been the associated increased cost.
      Methods: To perform this study, we used the time-derived activity-based costing
      (TDABC) technique to accurately assess the true cost of gastrointestinal
      procedures done with gastroenterologist-administered conscious sedation vs
      anesthesia-administered sedation in 2 areas of our practice that use
      predominantly conscious sedation or anesthesia-administered sedation. This type
      of study has never been reported using such an integrated approach. This study
      was performed on 2 different days in June 2015. Results: The true cost associated
      with anesthesia-administered sedation in our practice was associated with only 9%
      to 24% greater cost when the TDABC technique was applied. Conclusion:
      Gastrointestinal procedures with anesthesia-administered sedation are not as
      costly when all factors are considered. Using novel approaches to cost
      measurement, such as the TDABC, allows a total cost measurement approach across
      an episode of care that existing cost measurements in health care are incapable
      of.

PMID- 30225423
TI  - Venous Thromboembolism Prophylaxis: Inadequate and Overprophylaxis When Comparing
      Perceived Versus Calculated Risk.
AB  - Guidelines for venous thromboembolism (VTE) prophylaxis recommend appropriate
      risk stratification using risk estimation models as high risk or low risk
      followed by initiation of chemical or mechanical prophylaxis, respectively. We
      explored adherence to guidelines on the basis of the documentation of VTE
      prophylaxis. A retrospective medical record review of 437 consecutive adult
      patients (>=18 years) admitted to general medical wards under medicine service
      between January 1, 2015, and March 1, 2015, was performed. The primary outcome
      was appropriateness of risk stratification using the Padua Prediction Score.
      Secondary outcomes were appropriateness of type of prophylaxis (chemical vs
      mechanical) and cost-benefit analysis. We observed appropriate stratification
      based on the documented risk (compared with the calculated risk) in 54.9% of the
      patients (40.8% with low risk vs 72.1% with high risk; P<.001). Overall, 182 of
      240 low-risk patients received unnecessary chemical prophylaxis, whereas 23 of
      197 high-risk patients without contraindications for chemical prophylaxis
      received mechanical or no prophylaxis. No clinical VTE events were noted in the
      patients inappropriately assigned to mechanical or no prophylaxis. Also, 67.3% of
      patients with both low documented and low calculated risk and 74.5% of patients
      with low documented and high calculated risk received chemical prophylaxis,
      consistent with a tendency toward overtreatment. A total of 4068 annualized
      patient-days ($77,652/y) of inappropriate chemical prophylaxis were administered.
      In conclusion, estimation of the risk of VTE based on clinical impression was not
      congruent with the risk calculated using risk prediction models and was
      associated with a tendency toward overtreatment. These data support the inclusion
      of VTE risk calculators in electronic health record systems.

PMID- 30225424
TI  - Demographic Patterns Associated With Compliance in Pain Contract Patients: A
      Residency Clinic Experience.

PMID- 30225425
TI  - Beyond Solo Interventions: Working Toward Medication Optimization.

PMID- 30225426
TI  - Effect of Postdismissal Pharmacist Visits for Patients Using High-Risk
      Medications.
AB  - Objective: To determine whether a pharmacist visit after hospital dismissal for
      patients taking at least 1 medication that places patients at high risk for
      emergent hospital admissions (termed high-risk medication) would decrease the
      risk of hospital readmission at 30 days compared with usual care. Patients and
      Methods: This was a retrospective study at a tertiary care center conducted from
      July 26, 2013, through April 1, 2016. We reviewed outcomes among patients who did
      or did not have a post-hospital dismissal pharmacist visit immediately before a
      clinician visit. We included patients who were at least 18 years old and were
      taking at least 10 total medications at hospital dismissal, 1 or more of which
      were high-risk medications. A Cox proportional hazards model was used to compare
      the risk of 30-day readmission between the groups. Results: The study cohort
      included 502 patients in each group (pharmacist + clinician group and clinician
      only group). After adjusting for differences in background demographic
      characteristics, patients in the pharmacist + clinician group were significantly
      less likely to be readmitted to the hospital within 30 days postdismissal
      compared with the clinician-only group (hazard ratio, 0.49; 95% CI, 0.35-0.69;
      P<.001). Conclusion: Patients seen by a pharmacist immediately before a clinician
      visit after hospital dismissal had a lower risk of readmission than patients who
      had a clinician-only visit. Patients taking high-risk medications for hospital
      admissions are ideal candidates for pharmacist involvement.

PMID- 30225427
TI  - Adolescent Perinatal Outcomes in South West Sydney, Australia.
AB  - Objective: To compare perinatal outcomes, blood pressures throughout pregnancy,
      rates of hypertensive disorders of pregnancy, preeclampsia, gestational diabetes
      mellitus, and immediate obstetric outcomes in adolescents younger than 20 years
      at delivery and those in the 20- to 34-year age group. Patients and Methods:
      Questionnaires were administered to pregnant women at Campbelltown and Liverpool
      hospitals within South West Sydney, Australia, as part of a broader study of
      sleep-disordered breathing in pregnancy between February 1, 2009, and February
      28, 2013. Data collected included demographic data, blood pressure readings,
      pregnancy complications, delivery type, and neonatal outcomes. Adolescents were
      compared with older women using Student t tests and chi2 statistics. Results: A
      total of 103 adolescents were compared with 2291 women aged 20 to 34 years.
      Adolescents were more likely to be primiparous, had longer average gestations,
      and had lower pre-pregnancy body mass index. Adolescents had lower rates of
      cesarean section delivery and gestational diabetes mellitus. There was no
      significant difference in smoking rates, perinatal mortality rate, small for
      gestational age, intrauterine growth restriction, Apgar score of less than 7 at 5
      minutes, admission to special care nursery, or hypertensive disorder of pregnancy
      rates. Adolescents had lower booking systolic and diastolic blood pressures, and
      their highest antenatal systolic blood pressures were lower. Conclusion:
      Adolescents have birth outcomes to similar to those of their older counterparts.
      Adolescents had lower booking blood pressures. This may have implications for the
      screening and diagnosis of hypertensive disorders of pregnancy in adolescents.

PMID- 30225428
TI  - Epidemiologic Factors, Clinical Presentation, Causes, and Outcomes of Liver
      Abscess: A 35-Year Olmsted County Study.
AB  - Objective: To report the changing incidence, clinical presentation, microbiologic
      spectrum, and outcomes of pyogenic liver abscess (PLA) in Olmsted County,
      Minnesota, over the past 35 years. Patients and Methods: The Rochester
      Epidemiology Project was used to identify residents with PLA from January 1,
      1980, through December 31, 2014. The study included all patients older than 18
      years, with the diagnosis of PLA confirmed through radiographic review and
      microbiologic cultures. Results: In total, 72 patients received a diagnosis of
      PLA from 1980 through 2014. The age-adjusted incidence for men was 3.92 cases per
      100,000 person-years (95% CI, 2.76-5.09 cases per 100,000 person-years) compared
      with 1.87 cases per 100,000 person-years (95% CI, 1.15-2.59 cases per 100,000
      person-years) for women. Incidence was higher in the period from January 1, 2001,
      through December 31, 2014, than in the period from January 1, 1980, through
      December 31, 2000, for women (incidence rate ratio [IRR], 3.8; 95% CI, 1.43
      10.09; P=.007) but not for men (IRR, 0.99; 95% CI, 0.55-1.76; P=.96). Fifteen
      additional patients had postintervention PLA (1980-2000: n=3 of 29 [10.3%] vs
      2001-2015: n=12 of 58 [20.6%]). A significant association was seen between age-
      and sex-adjusted incidence rates of PLA and year of diagnosis (per year since
      1980: IRR, 1.04; 95% CI, 1.02-1.07; P<.001) after including postintervention PLA.
      Streptococcus milleri was the most common organism identified (52.5%). Organisms
      with multidrug resistance were more common in the period from 2001 through 2014
      than in the period from 1980 through 2000 (51% vs 14%; P=.005). The overall
      mortality rate of PLA was 16.8% (95% CI, 7.6%-25.0%) at 6 months. Conclusion: The
      incidence of PLA is increasing, probably because of increase in frequency of
      hepatobiliary interventions and organisms with multidrug resistance.

PMID- 30225429
TI  - Safety of Sedation for Patients Undergoing Bone Marrow Biopsy and Aspiration
      While Febrile.
AB  - Objective: To determine the risks and outcomes of providing sedation to febrile
      patients scheduled for bone marrow aspiration or biopsy procedures. Patients and
      Methods: During the 4-year period from January 1, 2013, through December 31,
      2016, data from the periprocedural courses of 12,134 consecutive patients in an
      outpatient procedure center at a large tertiary medical center were collected
      retrospectively and analyzed to determine whether febrile patients undergoing
      bone marrow aspiration and/or biopsy with propofol sedation present a unique
      patient safety risk. Results: Eighty-four patients (0.7%) had preprocedural
      temperatures of greater than or equal to 38.3 degrees C. Of these, 6 required
      unanticipated hospital admission for sustained hypoxemia and symptoms suggesting
      pneumonia. All 6 of these patients had a productive cough and room air oxygen
      saturations of less than 92% before their procedures. These 6 patients were
      diagnosed during their hospitalizations with either confirmed or presumed
      community-acquired pneumonia. All recovered without pulmonary sequelae. Only 2 of
      the other 78 febrile patients required unanticipated hospital admission, for both
      general weakness and dehydration. Conclusion: Our findings suggest that patients
      who are febrile and who also have productive coughs and oxyhemoglobin saturations
      by pulse oximetry of less than 92% would be best served with outpatient
      evaluation of their pulmonary symptoms before undergoing their elective bone
      marrow aspiration procedures. In contrast, febrile patients without pulmonary
      symptoms fare well.

PMID- 30225430
TI  - Clinical, Biochemical, and Radiological Characteristics of a Single-Center
      Retrospective Cohort of 705 Large Adrenal Tumors.
AB  - Objective: To characterize large adrenal tumors (>=4 cm in diameter) and to
      identify features associated with malignancy. Patients and Methods: We
      investigated the clinical, biochemical, and imaging characteristics in a large
      retrospective single-center cohort of patients with adrenal tumors of 4 cm or
      more in diameter during the period of January 1, 2000, through December 31, 2014.
      Results: Of 4085 patients with adrenal tumors, 705 (17%) had adrenal masses
      measuring 4 cm or more in diameter; of these, 373 (53%) were women, with a median
      age of 59 years (range, 18-91 years) and median tumor size of 5.2 cm (range, 4.0
      24.4 cm). Underlying diagnoses were adrenocortical adenomas (n=216 [31%]),
      pheochromocytomas (n=158 [22%]), other benign adrenal tumors (n=116 [16%]),
      adrenocortical carcinomas (n=88 [13%]), and other malignant tumors (n=127 [18%]).
      Compared with benign tumors, malignant tumors were less frequently diagnosed
      incidentally (45.5% vs 86.7%), were larger (7 cm [range, 4-24.4 cm] vs 5 cm
      [range, 4-20 cm]), and had higher unenhanced computed tomographic (CT)
      attenuation (34.5 Hounsfield units [HU] [range, 14.1-75.5 HU] vs 11.5 HU [range, 
      110 to 71.3 HU]; P<.001). On multivariate analysis, older age at diagnosis, male
      sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT
      attenuation were all found to be statistically significant predictors of
      malignancy. Conclusion: The prevalence of malignancy in patients with adrenal
      tumors of 4 cm or more in diameter was 31%. Older age, male sex, nonincidental
      mode of discovery, larger tumor size, and higher unenhanced CT attenuation were
      associated with an increased risk for malignancy. Clinical context should guide
      management in patients with adrenal tumors of 4 cm or more in diameter.

PMID- 30225431
TI  - Stereotactic Body Radiotherapy for Medically Inoperable Stage I-II Non-Small Cell
      Lung Cancer: The Mayo Clinic Experience.
AB  - Objective: To examine disease control and survival after stereotactic body
      radiotherapy (SBRT) for medically inoperable, early-stage non-small cell lung
      cancer (NSCLC) and determine associations of pretreatment 18F-fluorodeoxyglucose
      positron emission tomography (FDG-PET) maximum standardized uptake values
      (SUVmax), biologically effective dose, and mediastinal staging with disease
      control and survival outcomes. Patients and Methods: We retrospectively reviewed
      the cases of consecutive patients with FDG-PET-staged, medically inoperable NSCLC
      treated with SBRT at our institution between January 1, 2008, and August 4, 2014.
      Cumulative incidences of recurrence were estimated, accounting for the competing
      risk of death. Associations of SUVmax, biologically effective dose, and
      mediastinal staging with outcomes were evaluated using Cox proportional hazards
      regression models. Results: Among 282 patients, 2-year cumulative incidences of
      recurrence were 4.9% (95% CI, 2.6%-8.3%) for local, 9.8% (95% CI, 6.3%-14.2%) for
      nodal, 10.8% (95% CI, 7.0%-15.5%) for ipsilateral lung, 6.0% (3.3%-9.8%) for
      contralateral lung, 9.7% (95% CI, 6.3%-14.0%) for distant recurrence, and 26.1%
      (95% CI, 20.4%-32.0%) for any recurrence. The 2-year overall survival was 70.4%
      (95% CI, 64.5%-76.8%), and the 2-year disease-free survival was 51.2% (95% CI,
      44.9%-58.5%). Risk of any recurrence was significantly higher for patients with
      higher SUVmax (hazard ratio [per each doubling], 1.29 [95% CI, 1.05-1.59];
      P=.02). A similar association with SUVmax was observed when considering the
      composite outcome of any recurrence or death (hazard ratio, 1.23 [95% CI, 1.05
      1.44]; P=.01). The SUVmax was not significantly associated with other outcomes
      (P>=0.69). Two-year cumulative incidences of local recurrence for patients
      receiving 48 Gy in 4 fractions, 54 Gy in 3 fractions, or 50 Gy in 5 fractions
      were 1.7% (95% CI, 0.3%-5.6%), 3.7% (95% CI, 0.7%-11.4%), and 15.3% (95% CI, 5.9%
      28.9%), respectively (P=.02); this difference was independent of lesion size
      (P=.02). Conclusion: Disease control was excellent for patients who received SBRT
      for early-stage NSCLC, and this series represents the largest single-institution
      experience from the United States on SBRT for early-stage inoperable NSCLC.
      Higher pretreatment FDG-PET SUVmax was associated with increased risk of any
      recurrence, and the 50 Gy in 5 fractions dose prescription was associated with
      increased risk of local recurrence.

PMID- 30225432
TI  - Use of an Electronic Medical Record to Track Adherence to the Mediterranean Diet
      in a US Neurology Clinical Practice.
AB  - Objective: We describe our experience with routinely capturing and analyzing
      Mediterranean diet data via structured clinical documentation support tools built
      into the electronic medical record and describe adherence to the Mediterranean
      diet in patients at risk for either stroke or dementia in a US neurology clinical
      practice. Patients and Methods: The Mediterranean diet is associated with a
      reduced risk of stroke and dementia. The Department of Neurology at NorthShore
      University HealthSystem routinely evaluates patients at initial and annual
      outpatient visits using structured clinical documentation support (SCDS) tools
      built into the electronic medical record (EMR). For patient evaluations in our
      Vascular Neurology and Brain Health subspecialty clinics, SCDS tools in the EMR
      include the validated 14-item questionnaire for Mediterranean diet adherence
      (PREvencion con DIeta MEDiterranea [PREDIMED]) that autoscores, auto-interprets,
      writes to the progress note, and electronically captures data. Our study
      population includes patients seen at these clinics from July 1, 2015, through
      November 29, 2017. Results: At their initial office visit, 25.5% (95/373) of
      Brain Health patients scored 10 or more points ("strongly adherent") on the
      PREDIMED (median, 8; range, 0-14) whereas 6.7% (55/829) of Vascular Neurology
      patients achieved a score of 10 or more points (median, 6; range, 0-12). By
      contrast, 34.7% (2586/7447) of individuals in the original PREDIMED cohort were
      strongly adherent to the Mediterranean diet. Conclusion: PREDIMED scores can be
      electronically captured to tailor nutrition interventions by assessing baseline
      adherence at the time of their initial neurology clinic visit. Patients in our
      Midwestern US clinics were weakly adherent to the Mediterranean diet. This
      suggests a major opportunity for nutrition intervention and education in US
      neurology clinical practices, toward preserving and improving brain health.

PMID- 30225433
TI  - Fostering Choice Awareness for Shared Decision Making: A Secondary Analysis of
      Video-Recorded Clinical Encounters.
AB  - Objective: To assess the extent to which (1) clinicians, using or not using
      conversation aids, foster choice awareness during clinical encounters and (2)
      fostering choice awareness, with or without conversation aids, is associated with
      greater patient involvement in shared decision making (SDM). Patients and
      Methods: We randomly selected 100 video-recorded encounters, stratified by topic
      and study arm, from a database of 10 clinical trials of SDM interventions in 7
      clinical contexts: low-risk acute chest pain, stable angina, diabetes,
      depression, osteoporosis, and Graves disease. Reviewers, unaware of our
      hypothesis, coded recordings with the OPTION-12 scale to quantify the extent to
      which clinicians involved patients in decision making (SDM, 0-100 score). Blinded
      to OPTION-12 scale scores, we used a self-developed coding scale to code whether
      and how choice awareness was fostered. Results: Clinicians fostered choice
      awareness in 53 of 100 encounters. Fostering choice awareness was associated with
      a higher OPTION-12 scale score (adjusted [for using vs not using a conversation
      aid] predicted mean difference, 20; 95% CI, 11-29). Using a conversation aid was
      associated with a higher, nonsignificant chance of fostering choice awareness
      (N=31 of 50 [62%] vs N=22 of 50 [44%]; adjusted [for trial] P=.34) and with a
      higher OPTION-12 scale score, although adjusting for fostering choice awareness
      mitigated this effect (adjusted predicted mean difference 5.8; 95% CI, -1.3
      12.8). Conclusion: Fostering choice awareness is linked to a better execution of
      other SDM steps, such as informing patients or discussing preferences, even when
      SDM tools are not available or not used.

PMID- 30225434
TI  - Complement Regulatory Genetic Mutations in the Setting of Autoimmune Thrombotic
      Thrombocytopenic Purpura: A Case Series.
AB  - Objective: To explore the benefits of adding eculizumab for the treatment of
      refractory autoimmune thrombotic thrombocytopenic purpura (iTTP) with complement
      dysregulation. Patients and Methods: From January 1, 2014, through July 1, 2017,
      we identified patients with iTTP defined by ADAMTS13 (disintegrin and
      metalloproteinase with a thrombospondin type 1 motif, member 13) levels less than
      5% and the presence of ADAMTS13 inhibitor. Patients who progressed after
      receiving standard of care management for iTTP were subjected to a comprehensive
      evaluation to look for evidence of complement activation. Herein, we share our
      single-institute experience regarding the clinical course and treatment algorithm
      for 3 patients with refractory iTTP. Results: All the patients had clinical
      deterioration despite treatment with plasma exchange, corticosteroids, rituximab,
      and vincristine, which prompted us to look for evidence of complement activation
      and associated genetic mutations. Complement-related genetic aberrations were
      present in all 3 patients, who had had different degrees of complement
      activation. The first 2 patients did not benefit from eculizumab when treatment
      was started before complete clearance of inhibitors to ADAMTS13. However, they
      had durable remissions when eculizumab was introduced after clearance of ADAMTS13
      inhibitors. The third patient started eculizumab therapy after inhibitor levels
      were undetectable. Conclusion: We found eculizumab therapy to be effective in all
      3 patients. However, its efficacy was prominent only after clearance of
      antibodies against ADAMTS13 via therapeutic plasma exchange.

PMID- 30225435
TI  - Association of Immune-Mediated Cerebellitis With Immune Checkpoint Inhibitor
      Therapy.
AB  - Immune-mediated encephalitis related to immune checkpoint inhibitor therapy is a
      rare but increasingly described condition that can cause significant morbidity.
      There are several reported cases in the literature but no previously described
      cases of immune-mediated cerebellitis. We describe a case of acute cerebellitis
      that developed in a 20-year-old man with primary refractory Hodgkin lymphoma
      being treated with the immune checkpoint inhibitor nivolumab. After exposure to 3
      cycles of nivolumab, the patient had acute onset of headache, ataxia, nausea, and
      vomiting, with imaging findings of cerebellar edema, early tonsillar herniation,
      and early hydrocephalus. Immune-mediated cerebellar encephalitis was suspected
      and high-dose dexamethasone therapy (8 mg every 6 hours) was initiated. Within 4
      days of dexamethasone therapy, his symptoms greatly improved with near-complete
      resolution of symptoms after a 4-week taper. Differential diagnosis of his
      condition included viral cerebellitis and paraneoplastic cerebellar degeneration.
      In cerebellar encephalitis suspected to be due to immune checkpoint inhibitor
      therapy, prompt recognition and early initiation of high-dose corticosteroids is
      essential for symptom resolution and treatment success, including the prevention
      of hydrocephalus and tonsillar herniation. Currently, there are no evidence-based
      guidelines to guide the initial dose, type, or duration of corticosteroids.
      Further investigation is needed in the pathogenesis and treatment of cerebellar
      encephalitis related to immune checkpoint inhibitor therapy to effectively treat
      this rare, disabling condition.

PMID- 30225436
TI  - Targeting Physician Burnout Through Emotional Intelligence, Self-Care Techniques,
      and Leadership Skills Training: A Qualitative Study.

PMID- 30225437
TI  - Ethical Issues in Contemporary Clinical Genetics.
AB  - As genetic sequencing capabilities become more powerful and costs decline, the
      reach of genomics is expanding beyond research laboratories to the wards,
      outpatient clinics, and, with the marketing of direct-to-consumer testing
      services, patients' homes. Increasingly, patients receiving various diagnoses
      from cancer to cardiomyopathy-can reasonably expect to have conversations with
      their providers about indications for genetic testing. In this dynamic context, a
      grasp of the ethical principles and history underlying clinical genetics will
      provide clinicians with the tools to guide their practice and help patients
      navigate complex medical-psychosocial terrain. This article provides an overview
      of the salient ethical concerns pertaining to clinical genetics. The subject is
      approached with an emphasis on clinical practice, but consideration is also given
      to research. The review is organized around the temporal and informational
      sequence of issues commonly arising during the course of pretesting, testing, and
      posttesting phases of patient care. Drawing from medical, legal, and historical
      perspectives, this review covers the following topics: (1) informed consent, (2)
      return of results, and (3) privacy and confidentiality, and intends to equip
      readers with an appropriate foundation to apply ethical principles to genetic
      testing paradigms with an understanding of the contextual landscape against which
      these situations occur.

PMID- 30225438
TI  - Consensus-Based Treatment Approaches for Managing Concerning Behaviors in
      Patients on Long-term Opioid Therapy for Chronic Pain: Case-Based Applications.
AB  - Guidelines recommend careful monitoring of patients on long-term opioid therapy
      for chronic pain to assess for concerning medication-taking behaviors that may
      signal opioid misuse or the presence of a substance use disorder. However,
      specific management strategies to guide providers if concerning medication-taking
      behaviors emerge are lacking. Therefore, we recruited a Delphi panel-42 experts
      in chronic pain and opioid prescribing-to develop consensus-based treatment
      approaches to guide management of the 6 most common and concerning behaviors
      identified: missing prescriber appointments, taking opioids for symptoms other
      than pain, using more opioid medication than prescribed, asking for an increase
      in opioid dose, aggressive behavior, and alcohol and other substance use. The
      results of that process are published as a separate study. The purpose of the
      present study was to present clinical cases in which concerning medication-taking
      behaviors arise in the course of long-term opioid therapy and demonstrate for
      readers how the Delphi panel's consensus-based approaches could be applied.

PMID- 30225439
TI  - Integrated Care: A Disruptive Innovation for Extending Psychiatric Expertise to
      Primary Care Practices.

PMID- 30225440
TI  - A Clinical Decision Support Tool for Familial Hypercholesterolemia Based on
      Physician Input.
AB  - Objective: To develop clinical decision support (CDS) for familial
      hypercholesterolemia (FH), based on physician input obtained by a mixed methods
      approach. Introduction: Awareness, detection, and control of FH-a relatively
      common genetic disorder-is low. Clinical decision support could address knowledge
      gaps and provide point-of-care guidance for the management of FH. Methods: A 16
      question survey that assessed familiarity with FH and sought input on potential
      content of the CDS tool was emailed to 1161 clinicians including 208
      cardiologists. In addition, 4 physician focus groups were held to gather input on
      the structure and form of the CDS tool. This study took place between September
      12, 2016, and January 16, 2017. Results: The response rate to the survey was
      18.1%. Clinicians were overwhelmingly (97.6%) in favor of a CDS tool that assists
      in managing patients with FH at the point of care and this was confirmed in the
      focus group discussions. Key themes emerged during the focus groups including
      providers' knowledge and understanding of FH, facilitators and barriers to
      implementing a CDS tool, and suggestions for its design and content. Conclusion:
      Clinicians were supportive of development of a CDS tool to assist with the
      evaluation and treatment of FH and provided feedback related to the design and
      implementation of such a tool.

PMID- 30225441
TI  - Impact of Doximity Residency Navigator on Graduate Medical Education Recruitment.
AB  - Objective: To assess residency applicants' use and perceptions of Doximity
      Residency Navigator (DRN) and to analyze the impact of Doximity reputation
      rankings on application, interview acceptance, and match list ranking decisions.
      Participants and Methods: We developed and distributed a survey seeking feedback
      from residency applicants to describe their use of DRN during the 2017 residency
      recruitment and match process. The dates of the study were March 1, 2017, through
      May 8, 2017. Results: We received responses from 2152 of 12,617 applicants (17%)
      across 24 graduate medical education programs. Sixty-two percent of respondents
      (n=1339) used DRN during the residency application, interview, and match list
      process. Doximity reputation rankings were noted to be valuable or very valuable
      to 78% of respondents (958 of 1233). Overall, 79% of respondents (977 of 1241)
      reported that Doximity reputation rankings influenced their application,
      interview acceptance, or match list ranking decisions. When asked about the
      accuracy of Doximity reputation rankings, 56% of respondents (699 of 1240)
      believed that rankings were slightly accurate or not accurate. The most commonly
      used resources to research potential residency programs were residency program
      websites, American Medical Association resources, and DRN. Conclusion: Most
      survey respondents used DRN during the application, interview, and match ranking
      process. Doximity reputation rankings were found to be the most valuable resource
      in DRN, although more than 50% of responders had doubts about the accuracy of
      reputation rankings.

PMID- 30225443
TI  - At the Intersection of Patient Experience Data, Outcomes Research, and Practice:
      Analysis of HCAHPS Scores in Neurology Patients.
AB  - Objective: To assess variation in patient-reported experience in inpatient
      neurology patients. Patients and Methods: We retrospectively identified 1045
      patients 18 years and older admitted to a neurology service and discharged from
      January 1, 2013, through September 30, 2016, who completed Hospital Consumer
      Assessment of Healthcare Providers and Systems (HCAHPS) surveys. Multivariable
      logistic regression evaluated the associations of patient factors with HCAHPS
      measures. Key driver analysis identified associations between HCAHPS measures and
      the Global score (combination of 0-10 hospital rating and likelihood to
      recommend). Multivariable logistic regression compared HCAHPS scores between
      neurology patients and those admitted to a neurosurgery (n=2190) or internal
      medicine (n=3401) service during the same period. Results: Among patients
      admitted to a neurology service, overall (summary) scores did not vary
      significantly by diagnosis after adjustment for age, education, and overall
      health, but patients with neurologic diagnoses other than stroke, epilepsy, and
      neurodegenerative disease were more likely to report lower Pain Management scores
      compared with patients with cancer. Key driver analysis showed Care Transition
      scores as drivers of the Global score. After adjustment, general internal
      medicine service patients were more likely to report low Summary scores and
      neurosurgery service patients were significantly less likely to report low
      Summary scores compared with neurology service patients. Conclusion: Efforts to
      improve how neurology patients experience their care should be aimed at targeting
      patients' perceptions of pain management, and improving care transitions is an
      important first-priority target for improvement. This analysis may help other
      institutions improve hospital rating, value-based payments, and patient-centered
      outcomes.

PMID- 30225442
TI  - Reducing Door-to-Reperfusion Time for Mechanical Thrombectomy With a Multitiered
      Notification System for Acute Ischemic Stroke.
AB  - Objective: To reduce door-to-angiographic reperfusion (DTR) time to 120 minutes
      for patients presenting with acute ischemic stroke attributed to anterior
      circulation large-vessel occlusion amenable to endovascular mechanical
      thrombectomy. Patients and Methods: Patients treated with mechanical thrombectomy
      before (April 10, 2015, through April 11, 2016) and after (April 12, 2016,
      through May 10, 2017) implementation of a multitiered notification system were
      studied. Lean process mapping was used to assess inefficiencies with
      multidisciplinary triage. A 3-tiered paging platform, which rapidly alerts
      essential personnel of the acute ischemic stroke team at advancing decision
      points, was introduced. Results: Sixty-two patients were analyzed before and
      after implementation (34 vs 28, respectively). Following intervention, DTR time
      was reduced by 43 minutes (mean DTR, 170 minutes vs 127 minutes; P=.02). At 90
      day follow up, 5 of the 28 patients in the postintervention cohort (19%) had
      excellent neurologic outcomes, defined as a modified Rankin Scale score of 0,
      compared to 0 of 34 (0%) in the preintervention cohort (P=.89). Reductions were
      also seen in the length of stay on the neurocritical care service (mean, 6 vs 3
      days; P=.006), and total hospital charges for combined groups (mean, $100,083 vs
      $161,458; P<.001). Conclusion: The multitiered notification system was a feasible
      solution for improving DTR within our institution, resulting in reductions of
      overall DTR time, neurocritical care service length of stay, and total hospital
      charges.

PMID- 30225444
TI  - The Vascular-Renal Connection in Patients Hospitalized With Hypertensive Crisis:
      A Population-Based Study.
AB  - Objective: To determine the risks of acute kidney injury development and long
      term clinical outcomes of patients with hypertensive crisis. Patients and
      Methods: This was a population study of Olmsted County residents with
      hypertensive crisis between January 1, 2000, and December 31, 2008, with follow
      up until June 30, 2016. Results: The results demonstrated that those with
      underlying chronic kidney disease upon admission for hypertensive crisis, defined
      as a systolic blood pressure above 180 mm Hg or diastolic blood pressure above
      120 mm Hg, were more likely to develop acute kidney injury during hospitalization
      (odds ratio, 6.04; 95% CI, 1-26; P=.02). Hospitalization length of stay was
      increased when patients developed acute kidney injury during hypertensive crisis
      hospitalization (7.6+/-9 vs 3.4+/-4 days; P=.04). Furthermore, those who
      developed acute kidney injury had increased cardiac rehospitalization frequency
      over 10 years (87% vs 46%; P=.009). These results suggest that those with poor
      renal reserve are more likely to have further acute kidney damage in the setting
      of hypertensive crisis, likely due to decreased renal perfusion and neurohormonal
      dysregulation. Conclusion: In patients hospitalized for hypertensive crisis,
      chronic renal insufficiency was a risk factor associated with acute kidney injury
      development during hospitalization. Those who developed acute kidney injury had
      longer hospitalizations with increased rehospitalization frequency. Future
      studies are warranted to further investigate whether the preservation of renal
      function will improve clinical outcomes in hospitalized patients with
      hypertensive crisis.

PMID- 30225445
TI  - Cardiorespiratory Fitness Is Inversely Associated With Clustering of Metabolic
      Syndrome Risk Factors: The Ball State Adult Fitness Program Longitudinal
      Lifestyle Study.
AB  - Objective: The focus of this study was the association between the metabolic
      syndrome (MetSyn) and cardiorespiratory fitness (CRF) defined as maximal oxygen
      uptake (VO2max). Although previous research has shown a relationship between
      MetSyn and CRF, most studies are based on less objective measures of CRF and
      different cardiometabolic risk factor thresholds from earlier guidelines.
      Participants and Methods: The metabolic markers included in the present study
      were central obesity, elevated plasma triglycerides, elevated fasting high
      density lipoprotein cholesterol, impaired fasting plasma glucose, hypertension,
      or pharmacologic treatment for diagnosed hypertension, hypertriglyceridemia, low
      high-density lipoprotein cholesterol, or diabetes. A cohort of 3636 adults (1629
      women, 2007 men; mean +/- SD age, 44.7+/-12.3 years) completed CRF and metabolic
      risk factor assessment between January 1, 1971, and November 1, 2016. The CRF was
      defined as a measured VO2max from a cardiopulmonary exercise test on a treadmill,
      with a respiratory exchange ratio value of 1.0 or more. Results: Prevalence of
      MetSyn (>=3 factors) was 26% (n=953) in the cohort, with men having a greater
      likelihood for MetSyn compared with women (P<.001). The difference in VO2max
      between those individuals with MetSyn and those without was approximately 2.3
      (2.0-2.5) metabolic equivalents. Logistic regression analyses showed a
      significant inverse and graded association between quartiles of CRF and MetSyn
      for the group overall (P<.001), with odds ratios (95% CI) using the lowest
      fitness group as the referent group of 0.67 (0.55-0.81), 0.41 (0.34-0.51), and
      0.10 (0.07-0.14) for VO2max (P<.001). The sex-specific odds ratios were 0.25
      (0.18-0.34), 0.05 (0.02-0.10), and 0.02 (0.01-0.09) for women and 0.43 (0.31
      0.59), 0.19 (0.14-0.27), and 0.03 (0.02-0.05) for men (P<.001). Conclusion: These
      results with current risk factor thresholds and a large number of women
      demonstrate that low VO2max is associated with MetSyn.

PMID- 30225447
TI  - Comorbidities, Fragility, and Quality of Life in Heart Failure Patients With
      Midrange Ejection Fraction.
AB  - Objective: To assess the effects of comorbidities, fragility, and quality of life
      (QOL) on long-term prognosis in ambulatory patients with heart failure (HF) with
      midrange left ventricular ejection fraction (HFmrEF), an unexplored area.
      Patients and Methods: Consecutive patients prospectively evaluated at an HF
      clinic between August 1, 2001, and December 31, 2015, were retrospectively
      analyzed on the basis of left ventricular ejection fraction category. We compared
      patients with HFmrEF (n=185) to those with reduced (HFrEF; n=1058) and preserved
      (HFpEF; n=162) ejection fraction. Fragility was defined as 1 or more abnormal
      evaluations on 4 standardized geriatric scales (Barthel Index, Older Americans
      Resources and Services scale, Pfeiffer Test, and abbreviated-Geriatric Depression
      Scale). The QOL was assessed with the Minnesota Living with Heart Failure
      Questionnaire. A comorbidity score (0-7) was constructed. All-cause death, HF
      related hospitalization, and the composite end point of both were assessed.
      Results: Comorbidities and QOL scores were similar in HFmrEF (2.41+/-1.5 and
      30.1+/-18.3, respectively) and HFrEF (2.30+/-1.4 and 30.8+/-18.5, respectively)
      and were higher in HFpEF (3.02+/-1.5, P<.001, and 36.5+/-20.7, P=.003,
      respectively). No statistically significant differences in fragility between
      HFmrEF (48.6%) and HFrEF (41.9%) (P=.09) nor HFpEF (54.3%) (P=.29) were found. In
      univariate analysis, the association of comorbidities, QOL, and fragility with
      the 3 end points was higher for HFmrEF than for HFrEF and HFpEF. In multivariate
      analysis, comorbidities were independently associated with the 3 end points
      (P<=.001), and fragility was independently associated with all-cause death and
      the composite end point (P<.001) in HFmrEF. Conclusion: Comorbidities and
      fragility are independent predictors of outcomes in ambulatory patients with
      HFmrHF and should be considered in the routine clinical assessment of HFmrEF.

PMID- 30225448
TI  - Acute Benefits After Liposomal Bupivacaine Abdominal Wall Blockade for Living
      Liver Donation: A Retrospective Review.
AB  - Objective: To investigate whether the addition of liposomal bupivacaine abdominal
      wall blocks to a multimodal analgesic regimen improves postoperative numeric
      rating scale pain scores and reduces opioid consumption in patients undergoing
      living liver donation. Patients and Methods: We conducted a single-center,
      retrospective review of patients who underwent living liver donation from January
      1, 2011, through February 19, 2016, and received multimodal analgesia with (block
      group) or without (control group) abdominal wall blockade. The block solution
      consisted of liposomal bupivacaine (266 mg) mixed with 30 mL of 0.25%
      bupivacaine. Both groups received intrathecal hydromorphone. Main outcome
      measures were pain scores, opioid requirements, time to full diet, and bowel
      activity. Results: Postoperative day 0 pain scores were significantly better in
      the block group (n=29) than in the control group (n=48) (2.4 vs 3.5; P=.002) but
      were not significantly different on subsequent days. Opioid requirements were
      significantly decreased for the block group in the postanesthesia care unit (0 vs
      9 mg oral morphine equivalents; P=.002) and on postoperative day 0 (7 vs 18 mg
      oral morphine equivalents; P=.004). Median (interquartile range) time to full
      diet was 23 hours (14-30 hours) in the block group and 38 hours (24-53 hours) in
      the control group (P=.001); time to bowel activity was also shorter in the block
      group (45 hours [38-73 hours] vs 67 hours [51-77 hours]; P=.01). Conclusion:
      Abdominal wall blockade with liposomal bupivacaine after donor hepatectomy
      provides an effective method of postoperative pain control and decreases time to
      full diet and bowel activity.

PMID- 30225449
TI  - Joint Corticosteroid Injection Associated With Increased Influenza Risk.
AB  - Aging and immunocompromising conditions or medications may reduce influenza
      vaccine effectiveness. The high-dose vaccine has been used to improve vaccine
      response in patients 65 years and older. Because of systemic immunosuppressive
      effects, oral corticosteroids may reduce vaccine effectiveness; however, despite
      over half a century of use, no data are available regarding the effect of joint
      and bursa corticosteroid injection on influenza vaccine effectiveness. The aim of
      this retrospective study was to determine whether joint corticosteroid injection
      was associated with reduced influenza vaccine effectiveness. During the 5
      influenza seasons between August 1, 2012, and March 31, 2017, a total of 15,068
      major joint corticosteroid injections were given to patients residing in Olmsted
      County, Minnesota. Vaccinated patients receiving a major joint corticosteroid
      injection (n=4804) were at increased risk (relative risk, 1.52; 95% CI, 1.20
      1.93) for developing influenza compared with vaccinated control patients. Women
      younger than 65 years were at the highest risk, suggesting that perhaps the high
      dose vaccine should be considered for this group to enhance protection when
      possible.

PMID- 30225446
TI  - Association of Cardiac Structure and Function With Neurocognition in
      Hispanics/Latinos: The Echocardiographic Study of Latinos.
AB  - Objective: To study the associations of comprehensive measures of cardiac
      structure and function with multidimensional neurocognitive measures. Patients
      and Methods: The Echocardiographic Study of Latinos is a population-based cohort
      of Hispanic/Latino adults older than 45 years enrolled from October 1, 2011,
      through June 30, 2014. Neurocognitive measures included Word Fluency (WF), Brief
      Spanish English Verbal Learning Test (B-SEVLT), and Digit Symbol Substitution
      Test. The B-SEVLT included B-SEVLT-recall and B-SEVLT-sum. Echocardiographic
      measures included cardiac structure, systolic and diastolic function, and
      myocardial strain. Multivariable regression models were fit using survey
      statistics and sampling probabilities. Results: A total of 1794 participants
      (mean age, 56+/-0.5 years; 56% women) were included in the analysis. In the
      adjusted model, higher left ventricular mass index was associated with lower B
      SEVLT-sum and Digit Symbol Substitution Test scores. Left ventricular systolic
      dysfunction was associated with lower WF scores. Abnormal left ventricular
      geometry was associated with lower B-SEVLT-sum scores. Higher relative wall
      thickness was associated with B-SEVLT-recall and B-SEVLT-sum scores. Mitral
      annular relaxation velocities were associated with lower B-SEVLT-recall, B-SEVLT
      sum, and WF scores. Higher mitral inflow to annular early diastolic velocity
      ratio was associated with lower B-SEVLT-recall and B-SEVLT-sum scores. Diastolic
      dysfunction was associated with lower B-SEVLT-sum scores. Finally, lower global
      longitudinal strain was associated with lower WF scores. Conclusion: Alterations
      in cardiac structure, systolic and diastolic function, and myocardial strain were
      associated with worse neurocognitive function. Further study is needed to
      determine the mechanisms (ie, impairment of cerebral flow and silent brain
      infarctions) mediating these heart-brain associations.

PMID- 30225450
TI  - Flow-Mediated Slowing as a Methodological Alternative to the Conventional Echo
      Tracking Flow-Mediated Dilation Technique for the Evaluation of Endothelial
      Function: A Preliminary Report.
AB  - The Moens-Korteweg equation predicts changes in pulse wave velocity (PWV) after
      changes in arterial radius; therefore, an increase in arterial radius, as seen in
      a reactive hyperemia (RH) condition, should slow PWV over a given arterial
      segment. If this assumption is true, then the deceleration of PWV over the
      brachial artery (flow-mediated slowing [FMS]) should be an equivalent signal of
      endothelial function during a conventional RH flow-mediated dilation (FMD)
      procedure. Our aim was to compare FMS with FMD after RH in healthy individuals as
      part of a study that seeks to evaluate the clinical usefulness of FMS as a
      noninvasive approach to characterize endothelial function. This cross-sectional
      study included 25 healthy participants (18 women [72%]) with a mean +/- SD age of
      21.12+/-0.73 years. The FMD and FMS were simultaneously measured. A significant
      correlation was observed between both measures of FMS (absolute difference and
      percentage variation) and echo FMD: R=-0.42 (P=.04) and r=0.46 (P=.02),
      respectively. The FMS was shown to depend on the baseline brachial diameter, with
      smaller variations depicted for smaller baseline brachial diameters. It seems to
      be a promising and feasible method for measuring changes after RH, although
      further studies are needed to evaluate how this correlation holds in different
      clinical conditions and to demonstrate its clinical usefulness.

PMID- 30225451
TI  - From Taking First Steps to Hitting Our Stride.

PMID- 30225452
TI  - Improving Nonclinical and Clinical-Support Services: Lessons From Oncology.
AB  - Nonclinical and clinical-support personnel serve patients on the front lines of
      care. Their service interactions have a powerful influence on how patients
      perceive their entire care experience, including the all-important interactions
      with clinical staff. Ignoring this reality means squandering opportunities to
      start patients out on the right foot at each care visit. Medical practices can
      improve the overall care they provide by focusing on nonclinical and clinical
      support services in 5 crucial ways: (1) creating strong first impressions at
      every care visit by prioritizing superb front-desk service; (2) thoroughly
      vetting prospective hires to ensure that their values and demeanor align with the
      organization's; (3) preparing hired staff to deliver excellent service with a
      commitment to ongoing training and education at all staff levels; (4) minimizing
      needless delays in service delivery that can overburden patients and their
      families in profound ways; and (5) prioritizing the services that patients
      consider to be most important. We show how cancer care illustrates these
      principles, which are relevant across medical contexts. Without nonclinical and
      clinical-support staff who set the right tone for care at every service
      touchpoint, even the best clinical services cannot be truly optimal.

PMID- 30225453
TI  - Preparation for and Implementation of Shared Medical Appointments to Improve Self
      Management, Knowledge, and Care Quality Among Patients With Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia in adults and is
      associated with an increased risk of stroke, heart failure, and death. Therapy
      for this pervasive arrhythmia is complex, involving multiple options that chiefly
      manage symptoms and prevent stroke. Current therapeutic strategies are also of
      limited efficacy, and can present potentially life-threatening side effects
      and/or complications. Emerging research suggests that the burden of AF can be
      reduced by improving patient understanding of the arrhythmia and teaching
      patients to adopt and maintain lifestyle and behavior changes. Shared medical
      appointments (SMAs) have been successfully used to deliver education and develop
      patient coping and disease management skills for patients with complex needs, but
      there is a paucity of studies examining the use of SMAs for managing AF.
      Moreover, few studies have examined strategies for implementing SMAs into routine
      clinical care. We detail our approach for (1) adapting a patient-centered SMA
      curriculum; (2) designing an evaluation comparing SMAs to routine care on patient
      outcomes; and (3) implementing SMAs into routine clinical practice. We conclude
      that evaluation and implementation of SMAs into routine clinical practice
      requires considerable planning and continuous engagement from committed key
      stakeholders, including patients, family members, schedulers, clinical staff,
      nurse educators, administrators, and billing specialists.

PMID- 30225454
TI  - Offshore Pharmaceutical Trials: Evidence, Economics, and Ethics.

PMID- 30225455
TI  - Feasibility of an International Remote Simulation Training Program in Critical
      Care Delivery: A Pilot Study.
AB  - Objective: To determine the feasibility and effectiveness of a video-enabled
      remote simulation training program to teach a systematic, standardized approach
      to the evaluation and management of the critically ill patients as part of an
      international quality improvement intervention. Patients and Methods: In this
      pilot "train-the-trainer" prospective cohort study, we provided a remote
      simulation-based educational program for practicing clinicians from intensive
      care units involved in an international quality improvement project
      (www.icertain.org). Between February 21, 2014, and August 6, 2015, participants
      completed a self-guided online curriculum and participated in structured
      simulation training using web conference software with recording capabilities.
      The performance was assessed using a matched pair analysis at baseline and using
      standardized scenarios and a validated assessment tool postintervention.
      Participants rated their satisfaction with the training experience and confidence
      in implementing these skills in clinical practice. Results: Eighteen local
      champions from 8 hospitals in 7 countries in Asia, Europe, and South and Central
      America completed the educational program. Learners exhibited significant
      improvements in cumulative critical task performance during simulated critical
      care scenarios with training (60.3%-81.8%; P=.002). Most clinicians (94%)
      reported that they felt well prepared to manage the common critical care
      scenarios after training. These local champions have subsequently delivered this
      educational program to more than 800 international clinicians over a 4-year
      period. Conclusion: Insufficient training is a major barrier to the delivery of
      cost-effective critical care in many areas of the world. Video-enabled remote
      simulation training is a low-cost, feasible, and effective method to disseminate
      clinical skills to critical care practitioners in diverse international settings.

PMID- 30225456
TI  - Outpatient Dismissal With a Responsible Adult Compared With Structured Solo
      Dismissal: A Retrospective Case-Control Comparison of Safety Outcomes.
AB  - Objective: To test the hypothesis that patients dismissed alone in a sedation
      dismissal process (SDP) have no greater risk of adverse outcome compared with
      those who were dismissed with a responsible adult. Patients and Methods: We
      compared 2441 SDP patients undergoing 2703 procedures with 4923 unique control
      patients who underwent 5133 procedures between June 1, 2012, and March 31, 2017.
      Results: The rate of unplanned readmission related to the procedure was 0.11%
      (n=9), and there was no difference between SDP (0.07%) and controls (0.14%).
      Similarly, there was no difference in complication rates between SDP patients and
      controls when restricting to "all causes" unplanned readmissions within 24 hours
      and unplanned readmissions related to procedure. Conclusion: With proper
      preparation, short-acting anesthetic/sedation medications, and sound clinical
      judgment, the presence of a responsible adult escort is not associated with
      reduced risk following discharge after ambulatory anesthesia. This practice may
      lessen the hardships reported by patients in needing to obtain an escort and the
      inconveniences and delays experienced by ambulatory procedural facilities when
      patients arrive without a designated escort.

PMID- 30225457
TI  - Bone Marrow Biopsy Operator Experience and Impact on Aspirate, Biopsy, and
      Ancillary Testing Quality.
AB  - Objective: To assess the relationship between bone marrow (BM) biopsy operator
      experience and both specimen quality and ancillary testing utilization. Patients
      and Methods: We evaluated all referred and in-house (IH) BM biopsy specimens
      obtained over a contiguous 6-week period from April 3, 2017, to May 19, 2017. The
      BM specimens were assessed for the length of interpretable marrow, and aspirates
      were assessed for the presence of spicules. Subgroup comparisons included IH BM
      obtained by a trained team of nurses within our institution, patients clinically
      referred (CR) to our institution with outside-obtained BM specimens, and outside
      pathologist-referred (PR) consultation cases. Ancillary study usage was compared
      between the first 100 cases of each group. Results: A total of 1191 BM specimens
      were analyzed, including 600 IH, 288 CR, and 303 PR cases with biopsies and/or
      aspirates. The average interpretable biopsy lengths of IH, CR, and PR cases were
      16.0 mm, 10.0 mm, and 7.0 mm, respectively (P<.001). World Health Organization
      recommended length of 15 mm or more was achieved in 61.4%, 26.6%, and 19.1%,
      respectively (P<.001). Of the aspirates analyzed among IH, CR, and PR cases, 93%,
      71.3%, and 73.5% contained spicules, respectively (P<.001). Use of
      immunohistochemistry, flow cytometry, karyotype, and fluorescence in situ
      hybridization was higher in CR and PR cases than in IH cases (all P<.05). The IH,
      CR, and PR cases used on average 1.5, 2.8, and 4.8 immunohistochemistry stains
      per case (P<.001). Conclusion: Having a dedicated team of BM biopsy operators is
      likely one factor contributing to improved BM biopsy quality and a reduced need
      for ancillary testing.

PMID- 30225458
TI  - Risk Factors Associated With Health Care Utilization and Costs of Patients
      Undergoing Lower Extremity Joint Replacement.
AB  - Background: The Comprehensive Care for Joint Replacement program implemented by
      the Centers for Medicare and Medicaid Services did not incorporate risk
      adjustment for lower extremity joint replacement (LEJR). Lack of adjustment
      places hospitals at financial risk and creates incentives for adverse patient
      selection. Objective: To identify patient-level risk factors associated with
      health care utilization and costs of patients undergoing LEJR. Methods: A
      comprehensive search of research databases from January 1, 1990, through January
      31, 2016, was conducted. The databases included Ovid MEDLINE In-Process & Other
      Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register
      of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and SCOPUS
      and is reported according to the PRISMA (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses) statement. The search identified 2020 studies.
      Eligible studies focused on primary unilateral and bilateral LEJR. Independent
      reviewers determined study eligibility and extracted utilization and cost data.
      Results: Seventy-nine of 330 studies (24%) were included and were abstracted for
      analysis. Comorbidities, age, disease severity, and obesity were associated with
      increased costs. Increased number of comorbidities and age, presence of specific
      comorbidities, lower socioeconomic status, and female sex had evidence of
      increased length of stay. We found no significant association between indication
      for surgery and the likelihood of readmission. Conclusion: Developing a risk
      adjustment model for LEJR that incorporates clinical variables may serve to
      reduce the likelihood of adverse patient selection and enhance appropriate
      reimbursement aligned with procedural complexity.

PMID- 30225459
TI  - Lipid Profiles in Out-of-Hospital Sudden Unexpected Death.
AB  - Objective: To determine the association between serum lipid measurements and the
      occurrence of out-of-hospital sudden unexpected death (OHSUD). Patients and
      Methods: We compared 139 OHSUD cases (43 female patients [30.9%]) and 968
      controls (539 female patients [55.7%]) from Wake County, North Carolina, from
      March 1, 2013, through February 28, 2015. Individuals were included if they were
      aged 18 to 64 years and had lipid measurements in the 5 years before their death
      (cases) or the most recent health care encounter (controls). Covariates were
      abstracted from medical records for all subjects, and those with triglyceride
      (TG) levels greater than 400 mg/dL (to convert to mmol/L, multiply by 0.0259)
      were excluded for low-density lipoprotein (LDL)-related analyses. Results: By
      linear regression using age- and sex-adjusted models, cases of OHSUD had lower
      adjusted mean total cholesterol (170.3+/-52.2 mg/dL vs 188.9+/-39.7 mg/dL;
      P<.001), LDL cholesterol (90.9+/-39.6 mg/dL vs 109.6+/-35.2 mg/dL; P<.001), and
      non-high-density lipoprotein (HDL) (121.6+/-49.8 mg/dL vs 134.3+/-39.6 mg/dL;
      P<.001) levels and a higher adjusted TG/HDL-C ratio (4.7+/-7 vs 3+/-2.7; P<.001)
      than did controls. By logistic regression using age- and sex-adjusted models, the
      odds of OHSUD were elevated per unit increase in TG/HDL-C ratio (1.08; 95% CI,
      1.03-1.12). Conclusion: Out-of-hospital sudden unexpected death cases had more
      favorable levels of total cholesterol, LDL cholesterol, and non-HDL, possibly
      indicating a lack of association between traditional lipid cardiovascular risk
      factors and sudden unexpected death. A comparatively elevated TG/HDL-C ratio in
      cases may corroborate an evolving hypothesis of how vasoactive and prothrombotic
      remnant-like lipoprotein particles contribute to sudden unexpected death.

PMID- 30225460
TI  - Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome:
      Etiopathogenically Driven Analysis.
AB  - Objective: To characterize the etiologies and clinical features at diagnosis of
      patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these
      baseline features with survival using an etiopathogenically guided multivariable
      model. Patients and Methods: The Spanish Group of Autoimmune Diseases HLH Study
      Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed
      in internal medicine departments between January 3, 2013, and October 28, 2017.
      Results: The cohort consisted of 151 patients (91 men; mean age, 51.4 years).
      After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time
      to-event analyses for death identified a worse survival curve for patients with
      neoplasia (P<.001), mixed microbiological infections (P=.02), and more than 1
      infection (P=.01) and glucocorticoid monotherapy (P=.02). According to univariate
      analyses, platelets of less than 100,000/mm3 (hazard ratio [HR], 3.39; 95% CI,
      1.37-8.40), leukopenia (HR, 1.81; 95% CI, 1.01-3.23), severe hyponatremia (HR,
      1.61; 95% CI, 1.02-2.54), disseminated intravascular coagulation (HR, 1.87; 95%
      CI, 1.05-3.34), bacterial infection (HR, 1.99; 95% CI, 1.09-3.63), mixed
      microbiological infections (HR, 3.42; 95% CI, 1.38-8.46), and 2 or more
      infectious triggers (HR, 2.95; 95% CI, 1.43-6.08) were significantly associated
      with death. In contrast, peripheral adenopathies (HR, 0.63; 95% CI, 0.40-0.98)
      and the immunosuppressive drug/intravenous immunoglobulin/biological therapies
      (HR, 0.44; 95% CI, 0.20-0.96) were protective against all-cause mortality.
      Multivariable Cox proportional hazards regression analysis identified 2 or more
      infectious triggers (HR, 3.14; 95% CI, 1.28-7.68) as the only variable
      independently associated with death. Conclusion: The mortality rate of adult
      patients diagnosed with HLH exceeds 50%. Infection with more than 1
      microbiological agent was the only independent variable associated with mortality
      irrespective of the underlying disease, epidemiological profile, clinical
      presentation, and therapeutic management.

PMID- 30225461
TI  - Utility of Left Ventricular Ejection Fraction Measurements Before the
      Administration of Doxorubicin-Based Chemotherapy in Patients With Diffuse Large B
      Cell Lymphoma.
AB  - Objective: To determine the utility of routine measurements of left ventricular
      ejection fraction (LVEF) before the administration of doxorubicin-based
      chemotherapy (DOX) in patients with diffuse large B-cell lymphoma (DLBCL).
      Patients and Methods: We investigated the frequency of LVEF measurements before
      the initiation of therapy in 291 patients with DLBCL at our institution from
      January 1, 2001, through December 31, 2013, and reviewed whether LVEF varied in
      patients with an underlying risk of cardiac disease (CD), the relationship
      between LVEF and subsequent DLBCL treatment, and congestive heart failure (CHF)
      occurrence in DOX-treated patients. Results: Left ventricular ejection fraction
      was measured in 258 patients before the administration of chemotherapy and was
      not associated with underlying CHF risk (P=.94). Left ventricular ejection
      fraction was normal in 243 patients (94%) and low in 15 patients. Doxorubicin
      based chemotherapy was administered to 206 patients with normal LVEF (85%) vs 8
      patients with low LVEF (53%) (P=.006). However, when previous CD was factored
      out, LVEF did not influence subsequent treatment decisions (P=.51). Congestive
      heart failure occurred in 18 patients, and the risk was similar in patients
      treated with and without DOX. For all patients who had LVEF measured, CHF
      incidence did not differ between patients who received DOX and those who did not
      (P>.99). Moreover, there was no difference in CHF incidence after receiving DOX
      between those who had normal and low LVEF results (P=.45). Conclusion: The
      decision to administer DOX was influenced by LVEF status only when previous CD
      was factored out. Furthermore, CHF incidence posttreatment did not differ between
      patients who did and did not receive DOX. These preliminary findings challenge
      the practice of performing cardiac screening before DOX for patients with DLBCL.

PMID- 30225462
TI  - Flick-Spin Methodology for Improving Cannulation Success in Tortuous and Valve
      Rich Peripheral Veins.
AB  - Peripheral veins often contain tortuosities and valves that hinder the effective
      passage of intravenous catheters to the full extent of catheter length. This
      report describes a methodology termed flick-spin that has proven efficacious for
      venous catheter passage in tortuous and valve-rich peripheral veins. The method
      relies on (1) applying longitudinal tension to the vessel in an attempt to
      straighten it, (2) rotating or spinning the catheter along its longitudinal axis,
      and (3) flicking the skin or visible vein just beyond the catheter tip, all
      during catheter advancement. Additionally, lateral pressure may also be applied
      to the vessel-ie, proximal to the catheter tip and during catheter advancement-to
      fine-tune catheter tip direction. The report contains multiple illustrations to
      communicate the anatomic, physiologic, and technical underpinnings of the
      technique, as well as instructions for troubleshooting common problems.

PMID- 30225463
TI  - Adult Intestinal Botulism: A Rare Presentation in an Immunocompromised Patient
      With Short Bowel Syndrome.
AB  - The cholinergic heat-labile neurotoxin produced by Clostridium species is
      primarily responsible for the clinical manifestations of botulism. The classic
      phenotypic presentation of botulism consists of subacute descending flaccid
      paralysis with intact sensory function. Traditionally, it is classified into 3
      main forms (foodborne, wound-related, and infantile) on the basis of primary site
      of toxin entry into the human nervous system. Toxemia is the common
      pathophysiology in all forms of botulism. Adult intestinal toxemia botulism is an
      extremely rare form of the disease with pathogenesis similar to that of infant
      type botulism. Symptomatic adults usually have an anatomic abnormality in the
      gastrointestinal tract leading to changes in normal gut flora. The current case
      is an addition to the growing literature on this unusual clinical variant of
      botulism.

PMID- 30225464
TI  - Successful Renal Outcome in Membranoproliferative Glomerulonephritis Following
      Treatment of the Underlying Subtle Clone: A Case Report.
AB  - Membranoproliferative glomerulonephritis (MPGN) secondary to a monoclonal
      gammopathy is a rare glomerular disease and is defined as a monoclonal gammopathy
      of renal significance. The disease is characterized by glomerular monotypic
      immunoglobulin deposits and specific changes on light microscopy and electron
      microscopy. Immunochemistry is required to establish monoclonality, and electron
      microscopy helps to characterize the deposits ultrastructurally. Investigation
      for the underlying monoclonal protein should be done. We report a case of MPGN
      secondary to monoclonal gammopathy of renal significance that responded to
      treatment of the underlying clone with chemotherapy, resulting in improvement in
      renal function. Patients with MPGN and immunoglobulin deposition should be
      evaluated for a monoclonal protein to guide the management strategy.

PMID- 30225465
TI  - Dabrafenib and Trametinib Treatment for Erdheim-Chester Disease With Brain Stem
      Involvement.
AB  - Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis
      characterized by infiltration of organs by CD68+ and CD1a- lipid-laden
      histiocytes, including the central nervous system in more than a third of
      patients. Molecular analysis of ECD samples has demonstrated the prevalence of
      BRAF V600E mutations as high as 54%. Recently, vemurafenib became the only Food
      and Drug Administration-approved treatment for patients with ECD who carry the
      BRAF V600E mutation. However, dabrafenib has been suggested to have greater brain
      distribution. We describe a 44-year-old female patient treated from August of
      2015 through November 2017. She presented with a 2-year history of light
      headedness, fatigue, and vertigo. She was moderately dysmetric, diffusely
      hyperreflexic, and dysarthric in the bilateral upper and lower extremities. Her
      gait was wide-based. She had dysarthria and nystagmus on horizontal gaze
      bilaterally. Magnetic resonance imaging showed an extensive area of increased
      T2/fluid-attenuated inversion recovery signal in the brain stem, enhancement in
      the pons and midbrain, and thickening of the pituitary stalk. Positron emission
      tomography/computed tomography (PET/CT) and whole-body technetium Tc99m bone
      scintigraphy showed intense symmetrical radiotracer uptake in the distal femur
      and tibia bilaterally, which was biopsied. Immunohistochemistry was negative for
      BRAF V600E, but genomic sequencing revealed the mutation. The patient received
      combination therapy with dabrafenib and trametinib. Her nystagmus, dysarthria,
      dysmetria, and gait improved remarkably. Subsequent PET/CT and magnetic resonance
      imaging showed complete resolution of all radiographic evidence of disease. In
      this case report, we demonstrate the success of a combination therapy with
      dabrafenib and trametinib.

PMID- 30225466
TI  - Chemical Modification of CRISPR gRNAs Eliminate type I Interferon Responses in
      Human Peripheral Blood Mononuclear Cells.
AB  - Objectives: CRISPR/Cas9 is currently the primary tool used for genome editing in
      mammalian cells. To cleave and alter genomic DNA, both the Cas9 nuclease and a
      guide RNA (gRNA) must be present in the nucleus. One preferred method of
      introducing these reagents is direct transfection of a recombinant Cas9 protein
      complexed with a synthetic gRNA as a ribonucleoprotein (RNP) complex. It is well
      established from prior work in RNA interference that synthetic RNAs can induce a
      type I interferon (IFN) response that can limit the application of such methods
      both in vitro and in vivo. While the immunological properties of short siRNAs are
      well understood, little is known about the immune recognition of longer CRISPR
      gRNAs. The objective of our in vitro study was to investigate how the composition
      of the gRNA influences its recognition by human immune cells. Methods: The study
      was performed in vitro in human peripheral blood mononuclear cells (PBMCs). The
      PBMCs from healthy donor volunteers were treated with gRNA for 24 h, and the
      levels of type I IFNs in culture supernatants were measured by a multiplex enzyme
      linked immunosorbent chemiluminescent assay. Prior to the analysis in PBMCs, the
      physicochemical parameters and functionality of all nucleic acid constructs were
      confirmed by electrospray-ionization mass spectrometry and CRISPR/Cas9 gene
      editing assessment in HEK293-Cas9 cells, respectively. Results: We found that
      unmodified synthetic CRISPR gRNAs triggered a strong IFN response in PBMC
      cultures in vitro that could be prevented with chemical modification. Likewise,
      in vitro-transcribed single-guide RNAs (sgRNAs) also triggered a strong IFN
      response that could only be partially suppressed by phosphatase removal of the 5'
      triphosphate group. However, the process by which the gRNA is prepared (i.e.,
      chemically synthesized as a two-part crRNA:tracrRNA complex or in vitro
      transcribed as an sgRNA) does not directly influence the immune response to an
      unmodified gRNA. When experiments were performed in the HEK293 cells, only in
      vitro-transcribed sgRNA containing 5'-triphosphate induced IFN secretion.
      Conclusion: The results of our structure-activity relationship study, therefore,
      suggest that chemical modifications commonly used to reduce the immunostimulation
      of traditional RNA therapeutics can also be used as effective tools to eliminate
      undesirable IFN responses to gRNAs.

PMID- 30225467
TI  - Tackling problem nonlinearities & delays via asymmetric, state-dependent
      objective costs in MPC of an artificial pancreas.
AB  - The design of a Model Predictive Control (MPC) law for an Artificial Pancreas
      (AP) that automatically delivers insulin to people with type 1 diabetes mellitus
      is considered. An MPC law was recently proposed that exploits the simplicity of
      linear dynamical models, but is in two ways a 'nonlinear' departure of standard
      linear MPC, while circumnavigating the complexity of cumbersome, fully nonlinear
      MPC approaches. The first of two issues focused on is the nonlinearity of the
      control problem, and it is demonstrated how this can be tackled via asymmetric
      objective functions. The second issue is controller induced hypoglycemia
      resulting from the large delay in actuation and sensing. The proposed MPC
      strategy employs an asymmetric, state-dependent objective function that leads to
      a nonlinear optimization problem. The result is an AP controller with
      significantly elevated safety and comparable control performance. The
      contribution of this paper is a detailed in-silico analysis of the proposed
      control law, and a clinical demonstration of the benefits of asymmetric objective
      functions.

PMID- 30225468
TI  - A graphene quantum dot-based multifunctional two-photon nanoprobe for the
      detection and imaging of intracellular glutathione and enhanced photodynamic
      therapy.
AB  - A multifunctional nanosystem, which integrates biosensing, bioimaging, and
      therapeutic functions into a single nanoprobe, is of great significance for
      biosensing and biomedicine. Near-infrared (NIR) graphene quantum dots (GQDs) have
      emerged as an attractive bioimaging and therapy tool for exploring biological
      events because they can provide deep imaging penetration and low fluorescence
      background and produce 1O2 for PDT. Here, we reported a GQD-based multifunctional
      two-photon nanoprobe for intracellular tumor-related glutathione (GSH) detection
      and enhanced photodynamic therapy by reducing GSH levels in cancer cells. By
      taking the excellent quenching property of MnO2 nanosheets and the reduction
      ability of GSH, a GQD@MnO2 nanoprobe was developed through adsorption of MnO2
      nanosheets onto the surface of GQDs for sensing intracellular tumor-related GSH.
      The nanoprobe shows a highly sensitive response to GSH in aqueous solutions with
      a detection limit of 83 nM. It also exhibits a high selectivity toward GSH
      relative to other biomolecules and electrolytes. In addition, once endocytosed,
      the MnO2 nanosheets are reduced by intracellular GSH, simultaneously releasing
      GQDs and decreasing the level of GSH for highly efficient PDT.

PMID- 30225469
TI  - Quantitative temporal interrogation in 3D of bioengineered human cartilage using
      multimodal label-free imaging.
AB  - The unique properties of skeletal stem cells have attracted significant attention
      in the development of strategies for skeletal regeneration. However, there
      remains a crucial unmet need to develop quantitative tools to elucidate skeletal
      cell development and monitor the formation of regenerated tissues using non
      destructive techniques in 3D. Label-free methods such as coherent anti-Stokes
      Raman scattering (CARS), second harmonic generation (SHG) and two-photon excited
      auto-fluorescence (TPEAF) microscopy are minimally invasive, non-destructive, and
      present new powerful alternatives to conventional imaging techniques. Here we
      report a combination of these techniques in a single multimodal system for the
      temporal assessment of cartilage formation by human skeletal cells. The
      evaluation of bioengineered cartilage, with a new parameter measuring the amount
      of collagen per cell, collagen fibre structure and chondrocyte distribution, was
      performed using the 3D non-destructive platform. Such 3D label-free temporal
      quantification paves the way for tracking skeletal cell development in real-time
      and offers a paradigm shift in tissue engineering and regenerative medicine
      applications.

PMID- 30225470
TI  - Simultaneous hetero-atom doping and foreign-thiolate exchange on the Au25(SR)18
      nanocluster.
AB  - Atomically precise tuning of the structures of nanoclusters (NCs for short) is
      exciting and critical for tailoring the properties, capturing the structure
      property correlations, and strengthening the applications of these NCs. Metal
      exchange and ligand-exchange are two universal methods used to modify the NCs at
      the atomic level. In this work, simultaneous hetero-atom doping and hetero
      thiolate exchange are processed on the Au25 template by doping the Au25(SR)18 NC
      with Ag-SR' complexes (where SR and SR' represent different ligands), and these
      procedures are monitored by matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) and UV-vis spectrometry. Additionally, to obtain
      functional alloy NCs, Ag-SPhNH2 and Ag-SPhCOOH are used to dope the parent Au25(S
      C2H4Ph)18, which successfully functionalizes the capped ligands and alloys the
      metallic kernel at the same time. Our work will hopefully shed light on the
      preparation of alloy NCs with intriguing functions.

PMID- 30225471
TI  - On-line coupling between capillary electrophoresis and microscale thermophoresis
      (CE-MST); the proof-of-concept.
AB  - We demonstrate that microscale thermophoresis can be easily coupled with
      capillary electrophoresis in an on-line flow system (CE-MST), offering new
      potential possibilities. It takes advantage of sample separation and
      miniaturization prior to thermo-optical/MST analysis. No instrument modification
      is required. The future perspective is discussed.

PMID- 30225472
TI  - Expansion enhanced nanoscopy.
AB  - The advance of optical super-resolution fluorescence microscopy has
      revolutionized our vision of the subcellular world. Further improvement in the
      spatial resolution is of great significance for structural and functional
      investigations. The recently developed expansion microscopy (ExM), which achieves
      sub-diffraction imaging via physical expansion of the sample, provides a great
      opportunity for further resolution enhancement of existing optical super
      resolution techniques. However, although such combination seems apparent, several
      technical obstacles, especially the dramatic loss of fluorescence signal during
      ExM sample preparation, have hampered this goal. In this work, aiming at this
      challenge, we have developed new strategies to retain and increase the
      fluorescence of the expanded sample. With the new labeling methods, we have
      successfully made the labeling density of expanded samples sufficing the Nyquist
      sampling criteria for optical super-resolution imaging, such as stimulated
      emission depletion microscopy (STED) and super-resolution optical fluctuation
      imaging (SOFI). The newly developed expansion nanoscopic imaging (ExN)
      approaches, i.e. ExSTED and ExSOFI, demonstrated up to 4-fold resolution
      enhancement compared to standard STED and SOFI, providing a simple and effective
      way to realize high resolution imaging both at the cellular and tissue level.

PMID- 30225473
TI  - Correction: Determination of ferric ions using surface-enhanced Raman scattering
      based on desferrioxamine-functionalized silver nanoparticles.
AB  - Correction for 'Determination of ferric ions using surface-enhanced Raman
      scattering based on desferrioxamine-functionalized silver nanoparticles' by Fei
      Yan et al., Chem. Commun., 2013, 49, 7962-7964.

PMID- 30225474
TI  - A comprehensive approach providing a new synthetic route for bimetallic
      electrocatalysts via isoPOMs [M/Rh(Cp*)4W8O32] (M = Rh (1) and Ir (2)).
AB  - Polyoxometalates (POMs) are highly versatile materials if paired with various
      conducting supports. We here present a new prospective approach for obtaining
      advanced electrocatalytic systems via POMs (1 and 2) nanostructured on Ni foam
      (NF) to give bimetallic nanohybrid composite materials M0.4Ni0.6/WO3 (M = Rh (3)
      or Ir (4)). By this pathway, two rare isopolyoctatungstate-based organometallic
      clusters [Hx(MCp*)4W8O32].yH2O (in 1, M = Rh, x = 8, y = 23; in 2, M = Ir, x = 4,
      y = 17.33) have been synthesized via one-pot reactions using [Cp*MCl2]2 (Cp* =
      pentamethylcyclopentadienyl, M = Rh or Ir) and Na2WO4.2H2O in basic conditions.
      Compounds 1 and 2 were successfully nanostructured on the surface of commercially
      available NF and were thermally reduced to M0.4Ni0.6/WO3 (M = Rh (3) or Ir (4))
      after annealing at 400  degrees C for 8 h in a 15% H2/N2 atmosphere. Electrodes
      modified with the POMs 3 and 4 exhibited remarkable HER activities in a 1 M KOH
      solution and achieved a current density of 10 mA cm-2 at low overpotentials of
      about 67 and 35 mV versus RHE, with Tafel slopes of 56 and 34 mV dec-1,
      respectively.

PMID- 30225475
TI  - Confocal Raman microscopy combined with optical clearing for identification of
      inks in multicolored tattooed skin in vivo.
AB  - Raman measurements applied on freshly tattooed porcine skin ex vivo showed a
      possibility of obtaining the ink pigment related information in the skin. Based
      on these results, confocal Raman microscopy was used to identify the tattoo ink
      pigments of different colors in multicolored tattooed human skin in vivo. The
      Raman signatures of tattoo ink pigments were unique. Therefore, it could be shown
      that the applied method is successful for the identification of the tattoo ink
      pigments in human skin in vivo down to depths of approx. 50 MUm, which is
      sufficient to screen the entire epidermis and the top of the papillary dermis
      area on the forearm and leg skin sites. Additional application of the optical
      clearing technique in vivo by topical application of glycerol, combined with tape
      stripping removal of the uppermost stratum corneum layers and defatting allows
      the extension of depths of investigation in tattooed skin down to approx. 400
      MUm, i.e. to cover the entire papillary dermis and a large part of the reticular
      dermis. Thus, the tattoo ink pigments were identified in vivo and depth
      dependently in human tattooed skin confirming their presence in the papillary and
      reticular dermis. The proposed non-invasive in vivo Raman screening combined with
      optical clearing for identifying the tattoo pigments in the dermis can be an
      important task preceding a laser-based tattoo removal procedure and for
      determining the optimal laser parameters.

PMID- 30225476
TI  - Single atom detachment from Cu clusters, and diffusion and trapping on CeO2(111):
      implications in Ostwald ripening and atomic redispersion.
AB  - Ostwald ripening is a key mechanism for sintering of highly dispersed metal
      nanoparticles in supported catalysts. However, our microscopic understanding of
      such processes is still primitive. In this work, the atomistic mechanism of the
      Ostwald ripening of Cu on CeO2(111) is examined via density functional theory
      calculations. In particular, the detachment of a single Cu atom from ceria
      supported Cun (n = 2-10, 12, 14, 16, 18, and 20) clusters and trapping on the
      CeO2(111) surface is investigated in the absence and presence of CO adsorption.
      It is shown that the adsorption of CO on Cu reduces its detachment energy, which
      helps in the formation of single atom species on CeO2(111). In addition, the Cu1
      CO species is found to diffuse on the CeO2(111) surface with a much lower barrier
      than a Cu atom. These observations suggest an efficient mechanism for the Ostwald
      ripening of Cu clusters supported on ceria in the presence of CO. It is further
      predicted that the Cu1-CO species can eventually migrate to a step site on ceria,
      generating a stable single-atom motif with a relatively larger binding energy.
      Finally, the single Cu atom catalyst is shown to possess high activity for the
      oxygen reduction reaction.

PMID- 30225477
TI  - Surface enhanced resonance Raman spectroscopy (SERRS) for probing through plastic
      and tissue barriers using a handheld spectrometer.
AB  - The ability to probe through barriers and tissue non-invasively is an urgent
      unmet need in both the security and biomedical imaging fields. Surface enhanced
      Raman spectroscopy (SERS) has been shown to yield superior enhancement in signal
      over conventional Raman techniques. Furthermore, by utilising a resonant Raman
      reporter to produce surface enhanced resonance Raman spectroscopy (SERRS), even
      greater enhancement in chemical signal can be generated. Here we show the benefit
      of using red-shifted chalcogenpyrylium based Raman reporters for probing through
      large thicknesses of plastic and tissue barriers using a conventional Raman
      instrument. In addition, the benefit of using a resonant Raman reporter for
      superior levels of through barrier detection is demonstrated, and we aim to show
      the advantage of using resonant nanotags in combination with conventional Raman
      spectroscopy to probe through plastic and tissue barriers. Raman signals were
      collected from SERRS active nanotags through plastic thicknesses of up to 20 mm,
      as well as the detection of the same SERRS nanotags through up to 10 mm of tissue
      sections using a handheld conventional Raman spectrometer. The ability to detect
      SERRS-active nanotags taken up into ex vivo tumour models known as multicellular
      tumour spheroids (MTS), through depths of 5 mm of tissue is also shown. The
      advantages of applying multivariate analysis for through barrier detection when
      discriminating analytes with similar spectral features as the barrier is also
      clearly demonstrated. To the best of our knowledge, this is the first report of
      the assessment of the maximum level of through barrier detection using a
      conventional handheld Raman instrument for SERS applications as well as
      demonstration of the power of resonant nanotags for probing through barriers
      using conventional Raman spectroscopy.

PMID- 30225478
TI  - Impact of the water-compatible periphery on the dynamic and structural properties
      of benzene-1,3,5-tricarboxamide based amphiphiles.
AB  - The consequences of using saccharides versus tetra(ethyleneglycol) chains as
      water-compatible moieties on the morphology and dynamics of supramolecular
      polymers in aqueous solutions are investigated. The saccharides form many H-bonds
      with other saccharides within the polymer and with water, increasing the
      hydration of the fiber and changing its dynamics.

PMID- 30225479
TI  - Cobalt complexes of the chelating dicarboxylate ligand "esp": a paddlewheel-type
      dimer and a heptanuclear coordination cluster.
AB  - The coordination chemistry of Co(ii) with the chelating dicarboxylate ligand esp
      (esp = alpha,alpha,alpha',alpha'-tetramethyl-1,3-benzenedipropionate) is
      explored. We report here the bimetallic paddlewheel-type dimer, Co2(esp)2(EtOH)2
      (1), and a bowl-shaped, heptanuclear coordination cluster,
      Co7(OH)4(Hesp)2(esp)4(MeCN)2.4MeCN (2). Crystal structures of both complexes are
      reported as well as their magnetic properties, which indicate antiferromagnetic
      interactions among the Co(ii) ions.

PMID- 30225480
TI  - Universality in size-driven evolution towards bulk polarizability of metals.
AB  - The properties and characteristics of materials on the subnano/nano scale are
      very different from those of their bulk counterparts. The evolution of materials
      properties with size is the holy grail of nanoscience. An intriguing question
      then is: Can one predict what type of material (metal, semiconductor or
      insulator) an unidentified element will be, when in bulk quantities, solely from
      the properties it exhibits over a limited range of the subnano/nano size-regime?
      We demonstrate here that for nominally metallic elements (i.e., elements that are
      metals in bulk quantities) the answer to this question is "yes", and the very
      identity of the element also can be established. Most importantly, we show that
      the phenomenon of size-induced transition to metallicity, as gauged by
      polarizability, is characterized by features and trends that are universal for
      all metals. Combining numerical simulation data with an analytical model we
      introduce a universal constant and derive equations that express the universality
      explicitly.

PMID- 30225481
TI  - Glycodendron-rhenium complexes as luminescent probes for lectin sensing.
AB  - The design, synthesis and characterization of novel glycoconjugate luminescent
      probes based on dinuclear rhenium(i) complexes are reported. A multivalent
      platform bearing different carbohydrate moieties (Glc, Gal and Man) was used to
      target carbohydrate-binding proteins (lectins), exploiting the unique
      photophysical characteristics of a Re(i) luminophore for protein sensing. Our
      results show that these glycoconjugates, non-luminescent in aqueous medium, are
      able to specifically bind different lectins (ConA and PNA) with a consequent
      enhancement of emission intensity. These findings suggest the use of Re(i)-based
      glycoconjugates as switch-on luminescent probe tools in biological applications.

PMID- 30225482
TI  - Gas-phase ozonolysis of furans, methylfurans, and dimethylfurans in the
      atmosphere.
AB  - Furan and its methyl substituents, as promising alternative and renewable fuels
      and feedstock in the chemical industry, could be emitted to the atmosphere in a
      large scale and be degraded there by their reactions with OH, O3, NO3, Cl, etc.
      In this study, we investigate the mechanism of gas-phase ozonolysis of furans
      using quantum chemistry and kinetic calculations. The predicted rate coefficients
      agree well with the available experimental values for furan, 3-methylfuran (3
      MF), and 2,5-dimethylfuran (2,5-DMF), suggesting that their removal by ozonolysis
      could be comparable to their removal by OH radicals in the atmosphere,
      particularly for methylfurans. Rate coefficients for the ozonolysis of
      furaldehydes were also calculated. The ozonolysis of furans follows the Criegee
      mechanism by forming primary ozonides (POZs). RRKM-ME calculations show that the
      decomposition of the POZs is dominated by the formation of beta-unsaturated
      Criegee intermediates (CIs as [double bond splayed left]C[double bond, length as
      m-dash]CR-CHOO or [double bond splayed left]C[double bond, length as m-dash]CR
      C(OO)CH3, R = H or CH3). These CIs, formed with high excitation up to 250-280 kJ
      mol-1, would isomerize promptly to dioxirane and dioxolene products or dissociate
      promptly to a vinoxy-type radical and an OH radical. The dioxolenes would further
      isomerize to ether products containing another two carbonyl groups or one
      carbonyl group and one epoxide group, e.g., HC(O)OC(O)CH2CHO and HC(O)O-[CHOCH]
      CHO in furan. Formation of OH radicals is expected for furans with alkyl
      substitution at 3-/4-positions such as 3-MF and 2,3-DMF. The predicted fractional
      yield of 0.31 for OH radicals in the ozonolysis of 3-MF agrees well with the
      previous experimental values of 0.59 (with an uncertainty factor of ca. 1.5).

PMID- 30225483
TI  - Diflunisal-adjoined cobalt(iii)-polypyridyl complexes as anti-cancer stem cell
      agents.
AB  - We report a novel series of cobalt(iii)-polypridyl complexes, 4-6, that can
      selectively release diflunisal, a nonsteroidal anti-inflammatory drug, under
      reducing conditions. Remarkably, the 1,10-phenanthroline-bearing complex 5
      displays selective potency towards hard-to-kill cancer stem cells (CSCs) (IC50 =
      2.1 +/- 0.1 MUM) over bulk cancer (IC50 = 3.9 +/- 0.2 MUM) and normal cells (IC50
      = 21.2 +/- 1.3 MUM). This complex induces CSC apoptosis by DNA damage and
      cyclooxygenase-2 inhibition.

PMID- 30225484
TI  - Non-nuclear attractors in small charged lithium clusters, Limq (m = 2-5, q = +/
      1), with QTAIM and the Ehrenfest force partitioning.
AB  - In this investigation we explore the function and existence of the non-nuclear
      attractor (NNA) for a series of small charged lithium clusters Limq (m = 2-5, q =
      +/-1) using QTAIM and the Ehrenfest force F(r) partitioning schemes. The NNAs
      were found to be present in all of the Limq (m = 2-5, q = +/-1) clusters for
      QTAIM, in contrast none were found for F(r). We discovered that the anionic and
      cationic lithium dimers are limiting cases for minimal and maximal impact of the
      NNA related to the relative sparseness of total charge density rho(r)
      distributions respectively. Evidence is found that the NNA in the anionic dimer
      is in the process of being annihilated by two neighboring BCPs. We provide a
      measure of the size of the NNA and find for Limq (m = 2-5, q = +/-1) that larger
      NNAs correlate with increased Li-Li separations. The NNA was determined to be a
      persistent feature by varying the Li separations for the cationic and anionic
      dimers. Very large Li separations failed to induce an NNA in the F(r) anionic
      dimer and therefore we conclude that F(r) is unable to detect NNAs. The
      metallicity xi(rb) was also used to measure the sparseness of the distribution of
      rho(r) and significant metallic character, on the basis of xi(rb) > 1, was
      present for QTAIM but not for F(r), providing further evidence that F(r) cannot
      detect NNAs. Advantages of the use of Ehrenfest force F(r) partitioning scheme
      are discussed that include the design of nano-devices through tuning of the
      Ehrenfest potential VF(b) by the application of external forces such as a
      constant electric or strain field.

PMID- 30225485
TI  - Identification of the maze in the conformational landscape of fenchol.
AB  - The rotational spectrum of the bicyclic molecule fenchol (C10H18O, 1,3,3
      trimethylbicyclo[2.2.1]heptan-2-ol) - a biogenic volatile organic compound - was
      recorded in the gas phase using an impulse Fourier transform microwave
      spectrometer coupled to a supersonic jet expansion over the 2-20 GHz range.
      Quantum chemical calculations were performed to characterize the conformational
      landscape of the two diastereoisomers, endo-fenchol and exo-fenchol, with respect
      to the orientation of the hydroxyl group. The three most stable structures for
      each diastereoisomer were optimized at the MP2/6-311++G(2df,p) level of theory.
      Two of them were found to be very close in energy. Molecular parameters obtained
      from the analysis of observed signals led to the observation of one conformer per
      diastereoisomer. For the endo-fenchol molecule the rs geometry associated with
      the hydroxyl group was obtained, from the observation and analysis of the
      rotational spectra associated with the deuterated hydroxyl group. The nuclear
      quadrupolar hyperfine signature was identified. The hydroxyl group was found to
      be oriented into the direction of the methyl groups attached to C3, for the more
      stable conformer of endo-fenchol. For exo-fenchol, it is oriented into the methyl
      group attached to C1.

PMID- 30225486
TI  - Influence of the substituent on the phosphine ligand in novel rhenium(i)
      aldehydes. Synthesis, computational studies and first insights into the
      antiproliferative activity.
AB  - Cyrhetrenyl aldehyde derivatives [(eta5-C5H4CHO)Re(CO)2PR3] with R = methyl (Me,
      2a), phenyl (Ph, 2b), and cyclohexyl (Cy, 2c) were synthesized by a photochemical
      reaction from the starting material [(eta5-C5H4CHO)Re(CO)3] (1) and the
      corresponding phosphines. The complexes were fully characterized by FT-IR, 1H,
      13C and 31P NMR spectroscopy, elemental analysis and mass spectrometry. The
      molecular structures of 2a-c have also been determined. Electronic structure
      calculations by TD-DFT and electrochemical studies are in sound agreement with
      the effect of the substitution of one carbonyl group by a phosphine ligand.
      Additionally, the antiproliferative activity of complexes 1 and 2a-c was studied
      on the human cancer cell lines HT-29 and PT-45 using an MTT assay. Out of all new
      compounds, only the triphenylphosphine derivative 2b exhibited pronounced
      cytotoxic effects on both cell lines, being ca. 1.5 times more potent than
      cisplatin.

PMID- 30225487
TI  - Real-time characterization of uptake kinetics of glioblastoma vs. astrocytes in
      2D cell culture using microelectrode array.
AB  - Extracellular measurement of uptake/release kinetics and associated concentration
      dependencies provides mechanistic insight into the underlying biochemical
      processes. Due to the recognized importance of preserving the natural diffusion
      processes within the local microenvironment, measurement approaches which provide
      uptake rate and local surface concentration of adherent cells in static media are
      needed. This paper reports a microelectrode array device and a methodology to
      measure uptake kinetics as a function of cell surface concentration in adherent
      2D cell cultures in static fluids. The microelectrode array simultaneously
      measures local concentrations at five positions near the cell surface in order to
      map the time-dependent concentration profile which in turn enables determination
      of surface concentrations and uptake rates, via extrapolation to the cell plane.
      Hydrogen peroxide uptake by human astrocytes (normal) and glioblastoma multiforme
      (GBM43, cancer) was quantified for initial concentrations of 20 to 500 MUM over
      time intervals of 4000 s. For both cell types, the overall uptake rate versus
      surface concentration relationships exhibited non-linear kinetics, well-described
      by a combination of linear and Michaelis-Menten mechanisms and in agreement with
      the literature. The GBM43 cells showed a higher uptake rate over the full range
      of concentrations, primarily due to a larger linear component. Diffusion-reaction
      models using the non-linear parameters and standard first-order relationships are
      compared. In comparison to results from typical volumetric measurements, the
      ability to extract both uptake rate and surface concentration in static media
      provides kinetic parameters that are better suited for developing reaction
      diffusion models to adequately describe behavior in more complex culture/tissue
      geometries. The results also highlight the need for characterization of the
      uptake rate over a wider range of cell surface concentrations in order to
      evaluate the potential therapeutic role of hydrogen peroxide in cancerous cells.

PMID- 30225488
TI  - First-principles calculations of the electronic properties of SiC-based bilayer
      and trilayer heterostructures.
AB  - Recently, van der Waals (vdW) two-dimensional heterostructures have attracted
      great attention. The combination structures demonstrate unique properties that
      individual layers do not possess, which foretell promising future applications.
      Here, we investigate the structural and electronic properties of SiC/graphene,
      SiC/MoS2, and graphene/SiC/MoS2 vdW heterostructures using first-principles
      calculations. The SiC/graphene interface forms a p-type Schottky contact, which
      can be turned into an n-type Schottky contact by applying an external electric
      field. Moreover, a transition from a Schottky to an Ohmic contact at the
      interface can be triggered by varying the interlayer distance or applying an
      external electric field. The SiC/MoS2 interface forms a type-II heterostructure,
      in which the recombination of photoexcited charges will be greatly suppressed.
      The transition from type-II to type-III band alignment can be realized in the
      SiC/MoS2 heterostructure by applying a biaxial strain. This heterostructure also
      shows excellent optical absorption abilities in the visible and far-infrared
      range, which merits its application as a photocatalyst. The trilayer
      heterostructure exhibits a tunable Schottky barrier with different stacking
      patterns and the assembled graphene could act as a protective encapsulating layer
      on SiC/MoS2. The results show that graphene and MoS2 can tune and improve the
      electronic performance of SiC and demonstrate the promising application of SiC
      based heterostructures for nanoelectronics and nanophotonics.

PMID- 30225489
TI  - Correction: A combined stretching-tilting mechanism produces negative, zero and
      positive linear thermal expansion in a semi-flexible Cd(ii)-MOF.
AB  - Correction for 'A combined stretching-tilting mechanism produces negative, zero
      and positive linear thermal expansion in a semi-flexible Cd(ii)-MOF' by Prem Lama
      et al., Chem. Commun., 2014, 50, 6464-6467.

PMID- 30225490
TI  - Impact of nanoparticles on amyloid peptide and protein aggregation: a review with
      a focus on gold nanoparticles.
AB  - Society is increasingly exposed to nanoparticles as they are ubiquitous in nature
      and introduced as man-made air pollutants and as functional ingredients in
      cosmetic products as well as in nanomedicine. Nanoparticles differ in size, shape
      and material properties. In addition to their intended function, the side effects
      on biochemical processes in organisms remain unclear. Nanoparticles can
      significantly influence the nucleation and aggregation process of peptides. The
      development of several neurodegenerative diseases, such as Alzheimer's disease,
      is related to the aggregation of peptides into amyloid fibrils. However, there is
      no comprehensive or universal mechanism to predict or explain apparent
      acceleration or inhibition of these aggregation processes. In this work, selected
      studies and possible mechanisms for amyloid peptide nucleation and aggregation,
      in the presence of nanoparticles, are highlighted. These studies are discussed in
      the context of recent data from our group on the role of gold nanoparticles in
      amyloid peptide aggregation using experimental methods and large-scale molecular
      dynamics simulations. A complex interplay of the surface properties of the
      nanoparticles, the properties of the peptides, as well as the resulting forces
      between both the nanoparticles and the peptides, appear to determine whether
      amyloid peptide aggregation is influenced, catalysed or inhibited by the presence
      of nanoparticles.

PMID- 30225491
TI  - Is the formation of N-heterocyclic carbenes (NHCs) a feasible mechanism for the
      distillation of imidazolium ionic liquids?
AB  - We describe the synthesis of two tetrachloroindate ionic liquids used as probes
      to study the involvement of NHCs (N-heterocyclic carbenes) in the distillation of
      imidazolium derivatives. Atmospheric-pressure chemical ionization mass
      spectrometry (APCI-MS), electrospray ionization mass spectrometry (ESI-MS),
      atmospheric-pressure thermal desorption ion mass spectrometry (APTDI-MS) and
      laser-induced acoustic desorption (LIAD) were used to depict the possibility of
      the involvement of NHCs during the distillation process. Each type of imidazolium
      derivative showed a particular mechanism of distillation, pointing firmly to the
      dependence of both the cation and the anion natures to distil as ion pairs or
      NHCs. Ionic liquid 1-n-butyl-3-methylimidazolium tetrachloroindate (1a) exhibited
      a preference to distil as ion pairs, whereas 3,3'-(ethane-1,2-diyl)bis(1
      methyimidazolium)bis-tetrachloroindate (1b) may react with the Lewis acid anion,
      affording a bidentate NHC complex to distil. Thermodynamics, quantum theory of
      atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses of the ionic
      liquid 1a were also conducted and helped understand the preference for ion pairs
      instead of NHCs. The performed theoretical calculations did not forwent the
      possibility of NHC formation; however, they clearly indicated the high stability
      of the anions (Lewis acids in nature) and also indicated that the possible
      reaction between NHC and the anion is not favoured. The calculated thermodynamic
      values were in accordance with the features observed by MS and indicated ion
      pairs as the feasible species for the distillation of imidazolium-based ionic
      liquids.

PMID- 30225492
TI  - Cp*Co(iii)-Catalyzed oxidative [5+2] annulation: regioselective synthesis of 2
      aminobenzoxepines via C-H/O-H functionalization of 2-vinylphenols with ynamides.
AB  - A Cp*Co(iii)-catalyzed [5+2] C-H annulation reaction of 2-vinylphenols with
      ynamides was developed. The reaction led to the efficient synthesis of valuable 2
      aminobenzoxepines in high regioselectivity. Mild reaction conditions, good
      functional group tolerance, and moderate to good yields were observed. The
      synthetic utility was demonstrated by a gram-scale synthesis and further
      transformations of the products. Preliminary mechanistic studies were conducted,
      and a possible catalytic cycle was proposed.

PMID- 30225493
TI  - Transition-metal-free multinitrogenation of amides by C-C bond cleavage: a new
      approach to tetrazoles.
AB  - A metal-free brand-new one-pot multinitrogenation of amides for the chemo- and
      regioselective synthesis of 1,5-disubstituted tetrazoles has been developed. By
      means of electrophilic amide activation, and further C-C bond cleavage and
      rearrangement, a diverse set of functionalized 1,5-DST derivatives were
      selectively constructed under mild conditions. As showcased in the mechanisms,
      the chemoselectivity is easily switched by the selection of the starting
      materials in the reaction.

PMID- 30225494
TI  - A simple fluorescence biosensing strategy for ultrasensitive detection of the BCR
      ABL1 fusion gene based on a DNA machine and multiple primer-like rolling circle
      amplification.
AB  - A one-step, rapid fluorescence biosensing method has been developed for
      ultrasensitive detection of the BCR-ABL1 fusion gene based on a
      polymerase/nicking endonuclease DNA machine and multiple primer-like rolling
      circle amplification (RCA). In the strategy, the BCR-ABL1 fusion gene can be
      specifically identified by using a dual probe to form a three-way junction
      structure (3-WJ). Then the 3-WJ based DNA machine is driven by polymerase and
      nicking endonuclease to generate a large number of triggers, initiating a
      downstream RCA reaction. The introduction of two nicking endonuclease recognition
      sites into a circular DNA template makes RCA occur in a multiple primer-like
      manner, achieving exponential growth of the signal. Benefiting from the cascade
      amplification, the developed method generates a wide linear response from 10 fM
      to 1 nM with a low detection limit of 5.52 fM. In addition, the one-step
      operation allows the assay to be completed within 60 min and acceptable recovery
      is obtained in complex samples. These merits endow the biosensing strategy with
      certain potential for the clinical diagnosis and scientific research of the BCR
      ABL1 fusion gene.

PMID- 30225495
TI  - Dimericursones A and B: two unprecedented hexacyclic dimeric diterpenoids from
      the root barks of Jatropha curcas.
AB  - Dimericursones A and B (1 and 2), two unprecedented hexacyclic dimeric
      diterpenoids, were obtained from the root barks of Jatropha curcas. Their
      structures were elucidated by extensive spectroscopic analysis, electronic
      circular dichroism calculations, and single-crystal X-ray diffraction.
      Dimericursone B (2) showed significant inhibition on nitric oxide production of
      lipopolysaccharide-induced RAW264.7 macrophages with IC50 values of 5.65 MUM.

PMID- 30225496
TI  - High frequency acoustic permeabilisation of drugs through tissue for localised
      mucosal delivery.
AB  - The majority of infectious diseases enter the body through mucosal membranes that
      line the ocular, nasal, oral, vaginal and rectal surfaces. As infections can be
      effectively prevented by instigating a local immune response in the immunocyte
      rich regions of the mucosa, an efficacious route of vaccine administration is to
      directly target their delivery to these surfaces. It is nevertheless challenging
      to provide sufficient driving force to penetrate both the mucus lining as well as
      the epithelial barrier of the mucosal surfaces, which are designed to effectively
      keep foreign entities out, but not excessively such that the therapeutic agent
      penetrates deeper into the vascularised submucosal regions where they are mostly
      taken up by the systemic circulation, thus resulting in a far weaker immune
      response. In this work, we demonstrate the possibility of controllably localising
      and hence maximising the delivery of both small and large molecule model
      therapeutic agents in the mucosa of a porcine buccal model using high frequency
      acoustics. Unlike their low (kHz order) frequency bulk ultrasonic counterpart,
      these high frequency (>10 MHz) surface waves do not generate cavitation, which
      leads to large molecular penetration depths beyond the 100 MUm order thick
      mucosal layer, and which has been known to cause considerable cellular/tissue
      damage and hence scarring. Through system parameters such as the acoustic
      irradiation frequency, power and exposure duration, we show that it is possible
      to tune the penetration depth such that over 95% of the delivered drug are
      localised within the mucosal layer, whilst preserving their structural integrity.

PMID- 30225497
TI  - Rapid screening of anti-tumor metastasis drugs targeting integrin macrophage
      antigen-1 using immobilized cell capillary electrophoresis.
AB  - In this research a method called immobilized cell capillary electrophoresis
      (ICCE) was established under approximately physiological conditions for rapid
      screening of anti-tumor metastasis drugs targeting integrin macrophage antigen-1
      (MAC-1). In this method, separation and purification of the target receptors on
      cell membranes was unnecessary, thus, maintaining their natural conformation and
      bioactivity. MAC-1-, CD11b-, or CD18-overexpressing HEK293 cells (human embryonic
      kidney) were cultured and immobilized on the inner wall of capillaries as
      stationary phase, and their interactions with lactosyl derivative Gu-4 (positive
      control)/dimethylsulfoxide (DMSO; negative control) were studied using ICCE.
      Using this method, 29 phenylethanoid glycosides from Cistanches Herba were
      screened, and the binding kinetic parameters (K, ka, kd, and k') of active
      compounds were calculated, and the specific subunits of MAC-1 were determined.
      Then, molecular docking studies were performed to discover the direct interaction
      sites between active compounds and MAC-1, and the order of Glide-calculated
      Emodel value obtained from the molecular docking study is consistent with that of
      the binding constants obtained using ICCE. Finally, pharmaceutical efficacy
      assays in vitro and in vivo were carried out to show that the anti-tumor
      metastasis activity of the active compound had better pharmaceutical efficacy and
      lower toxic side effects. The method was verified to be valid and practical for
      further use, and it is expected that it will be transferred to capillary array
      electrophoresis for use in high-throughput drug screening.

PMID- 30225498
TI  - Nitrate-induced and in situ electrochemical activation synthesis of oxygen
      deficiencies-rich nickel/nickel (oxy)hydroxide hybrid films for enhanced
      electrocatalytic water splitting.
AB  - Hydrogen produced by electrochemical water splitting offers a hopeful and
      renewable solution for addressing the global energy crisis; however, development
      of highly efficient non-noble-metal electrocatalysts remains a big challenge.
      Herein, we report a facile strategy to fabricate oxygen deficiencies-rich
      nickel/nickel (oxy)hydroxide hybrid films as efficient electrocatalysts for water
      splitting by in situ oxygen evolution reaction (OER) activation. Under OER
      conditions, the originally deposited Ni films from the ethaline-based deep
      eutectic solvent (DES) undergo a structural rearrangement with a phase
      transformation in the oxidation state from Ni(ii) to Ni(iii) at the surface. The
      change is coupled with an increase in oxygen deficiencies and a pronounced
      defective precursor is induced by the addition of nitrate ions, providing
      structural disordering and boosting the intrinsic activity of the catalyst, which
      strongly enhances the water splitting performance.

PMID- 30225499
TI  - Validation of a quantitative PCR based detection system for indoor mold exposure
      assessment in bioaerosols.
AB  - Determination and assessment of airborne fungal particles is complex and results
      of different sampling and analytical strategies are hard to compare due to
      limitations of each of the techniques. Here, an indoor mold detection system
      based on quantitative polymerase chain reaction (qPCR) is described and validated
      for its reliability and stability to identify airborne fungal particles
      collected. Data obtained from testing the system with fungal DNA, spore
      suspensions and bioaerosols indicated a need for spiking and normalization of
      measurements due to material loss and assay specific bias. Considering the loss
      of material during sample processing, detection limits defined for suspensions of
      Tritirachium oryzae spores were roughly 18 spores per sample. Detection of fungal
      spore mixtures nebulized under controlled conditions in a bioaerosol chamber
      showed generally 2-3 times higher normalized values measured with the molecular
      system compared to cultivation. Data obtained from a mold infested indoor
      sampling site and its corresponding outdoor reference measurement showed good
      correlations between qPCR and high-throughput sequencing (rho = 0.83, p < 0.01),
      if Cladosporium species were excluded. Taking necessary data normalization into
      account, the described qPCR detection system shows great potential to complement
      commonly used culture based approaches with the aim to improve the precision of
      indoor mold assessments. In contrast to already available qPCR assays that detect
      certain molds on a species level, this system covers a broad range of relevant
      fungal communities, serving as a promising alternative to high-throughput
      sequencing to identify indoor molds.

PMID- 30225500
TI  - Coupling FeSe2 with CoSe: an effective strategy to create stable and efficient
      electrocatalysts for water oxidation.
AB  - A novel CoSe/FeSe2 nanohybrid electrocatalyst was prepared by a simple one-step
      hydrothermal method. Owing to the unique interface structure, abundant internal
      defects, good hydrophilia and electrical coupling effects between different
      components, the hybrid shows enhanced oxygen evolution reaction (OER)
      performances, better than those of the individual CoSe and FeSe2.

PMID- 30225501
TI  - Barium-catalyzed C-OH/P-H dehydrative cross-coupling for C-P bond construction.
AB  - A barium-catalyzed C-OH/P-H dehydrative cross-coupling protocol for the
      construction of C-P bonds was developed. This reaction was performed in an
      environmentally benign manner with water as the only by-product. A variety of
      allylic phosphorus compounds can be isolated in good to excellent yields.

PMID- 30225502
TI  - Construction of NIR luminescent polynuclear lanthanide-based nanoclusters with
      sensing properties towards metal ions.
AB  - Two types of 4- and 9-metal lanthanide-based nanoclusters [Ln2Zn2(L1)2(OAc)6] (Ln
      = Yb (1) and Er (2)) and [Yb9L2(L3)2(OAc)15(OH)8(H2O)2(DMF)] (3) were constructed
      using two Schiff base ligands that have long backbones with two and three phenyl
      groups. The molecular sizes of 1-2 and 3 are about 7 * 10 * 23 A and 11 * 17 * 22
      A, respectively. These clusters exhibit typical NIR luminescence of lanthanide
      ions. Interestingly, 3 exhibits luminescent sensing of metal ions and exhibits
      high sensitivities towards Cd2+ and Co2+ ions at the ppm level.

PMID- 30225503
TI  - Icariin and icaritin recover UVB-induced photoaging by stimulating Nrf2/ARE and
      reducing AP-1 and NF-kappaB signaling pathways: a comparative study on UVB
      irradiated human keratinocytes.
AB  - Icariin (ICA) and icaritin (ICT) exhibit many pharmacological functions including
      anti-osteoporosis, anti-cardiovascular, and anti-cancer activities; however,
      there are few comprehensive studies that track the detailed effects on UVB
      induced photoaging. The recovery effects of ICA and ICT were investigated in UVB
      irradiated human keratinocytes (HaCaTs). The results indicated that ICT and ICA
      showed strong radical scavenging activity, and the reactive oxygen species (ROS)
      scavenging activity of ICT was superior. UVB-induced matrix metalloproteinase-1
      (MMP-1) expression was blocked by ICA via the inhibition of mitogen-activated
      protein kinase/activator protein 1 (MAPK/AP-1), which directly reduced
      extracellular matrix (ECM) degradation. ICT activated nuclear factor erythroid 2
      related factor 2 (Nrf2) to improve the anti-oxidative stress capacity and
      suppress nuclear factor-kappaB (NF-kappaB) activation, decreasing vascular
      endothelial growth factor (VEGF) protein, and inflammatory cytokines induced ECM
      degrading enzyme secretion. Moreover, ICT was more advantageous to improve
      transforming growth factor beta 1 (TGF-beta1) and procollagen type I expression
      than ICA, promoting the synthesis of collagen. Therefore, ICA and ICT have
      potential to treat UVB-induced oxidative stress, inflammation and photoaging, and
      will be posited as a novel strategy to alleviate photodamage.

PMID- 30225504
TI  - Pyrazolone: a powerful synthon for asymmetric diverse derivatizations.
AB  - As a powerful synthon, pyrazolone has widely been exploited for the construction
      of various chiral pyrazoles/pyrazolones which hold great potential in the
      development of pharmaceutical chemistry, coordination chemistry and functional
      materials. Benefited from the diversity and multiple active sites of the starting
      materials, such as 4-nonsubstituted/4-monosubstituted pyrazolones and alpha,beta
      unsaturated pyrazolones, large numbers of strategies for the asymmetric synthesis
      of various pyrazoles/pyrazolones have been developed successfully in the past few
      years. This feature article summarizes these excellent research studies since
      2015, including some efforts by our group. Based on the structural feature of the
      final products, this feature article is divided into four sections, including the
      catalytic asymmetric synthesis of 4-monosubstituted, 4-disubstituted, fused and
      spiro pyrazoles/pyrazolones. Schematic illustrations are given for some
      representative examples in each section.

PMID- 30225505
TI  - PbTeGeO6: polar rosiaite-type germanate featuring a two dimensional layered
      structure.
AB  - Polar rosiaite-type germanate PbTeGeO6 (PTGO) was grown from TeO2 flux. It
      exhibits a two dimensional layered structure composed of [TeGeO6]2- sheets with
      Pb2+ separation between the sheets. The second harmonic generation intensity of
      the title compound is about 1.5 times that of KH2PO4. The first principles
      calculation was performed to investigate its electronic structure, refractive
      indices and nonlinear optical properties.

PMID- 30225506
TI  - Synthesis of alpha-amino ketones through aminations of umpoled enolates.
AB  - An efficient synthesis of alpha-amino ketones is developed using the umpolung
      strategy. Umpoled enolates such as N-alkenoxypyridinium salts react smoothly with
      diverse amines to give alpha-amino ketones via an SN2' pathway. This umpolung
      strategy overcomes the drawbacks of traditional methods such as the need for
      prefunctionalized ketone derivatives. Our method also offers good chemical yields
      and high functional group tolerance.

PMID- 30225507
TI  - Highly sensitive detection of exosomes by SERS using gold nanostar@Raman
      reporter@nanoshell structures modified with a bivalent cholesterol-labeled DNA
      anchor.
AB  - Exosomes, as important signal transmitters, play a key role in intercellular
      communication, especially in cancer metastasis. There is considerable evidence
      that exosomes can be used as an indicator of cancer. However, convenient and
      sensitive methods for detecting exosomes are still technically challenging. Here,
      we present a convenient and highly sensitive surface-enhanced Raman scattering
      (SERS) based method by combining immunoaffinity, SERS nanoprobes, and portable
      Raman devices for specific isolation and accurate quantification of exosomes. To
      construct the SERS-based biosensor, the surfaces of gold nanostar@4
      mercaptobenzoic acid@nanoshell structures (AuNS@4-MBA@Au) are modified with a
      bivalent cholesterol (B-Chol)-labeled DNA anchor to prepare SERS nanoprobes.
      Exosomes are specifically captured by immunomagnetic beads, and then SERS
      nanoprobes are fixed on the surface of exosomes by hydrophobic interactions
      between cholesterol and lipid membranes, thus forming a sandwich-type
      immunocomplex. The immunocomplex can be magnetically captured and produce
      enhanced SERS signals. In the absence of exosomes, the sandwich-type
      immunocomplex cannot be formed, and thus negligible SERS signals are detected.
      The degree of immunocomplex assembly and the corresponding SERS signals are
      positively correlated with the exosome concentration over a wide linear range of
      40 to 4 * 107 particles per MUL and the limit of detection is as low as 27
      particles per MUL. Consequently, a sensitive and simple strategy for detection of
      exosomes is successfully constructed. We believe that our biosensor has
      considerable potential as a convenient and highly sensitive quantification tool
      to detect exosomes in biological samples.

PMID- 30225508
TI  - Biomimetic water channels: general discussion.

PMID- 30225509
TI  - Towards organogenesis and morphogenesis in vitro: harnessing engineered
      microenvironment and autonomous behaviors of pluripotent stem cells.
AB  - Recently, researchers have been attempting to control pluripotent stem cell fate
      or generate self-organized tissues from stem cells. Advances in bioengineering
      enable generation of organotypic structures, which capture the cellular
      components, spatial cell organization and even some functions of tissues or
      organs in development. However, only a few engineering tools have been utilized
      to regulate the formation and organization of spatially complex tissues derived
      from stem cells. Here, we provide a review of recent progress in the culture of
      organotypic structures in vitro, focusing on how microengineering approaches
      including geometric confinement, extracellular matrix (ECM) property modulation,
      spatially controlled biochemical factors, and external forces, can be utilized to
      generate organotypic structures. Moreover, we will discuss potential technologies
      that can be applied to further control both soluble and insoluble factors
      spatiotemporally in vitro. In summary, advanced engineered approaches have a
      great promise in generating miniaturized tissues and organs in a reproducible
      fashion, facilitating the cellular and molecular understanding of embryogenesis
      and morphogenesis processes.

PMID- 30225510
TI  - A gold isocyanide complex with a pendant carboxy group: orthogonal molecular
      arrangements and hypsochromically shifted luminescent mechanochromism.
AB  - The epistatic double hydrogen bonds that arise from the presence of a pendant
      carboxy group in a gold isocyanide complex result in strong aurophilic
      interactions in a magenta-emitting polymorph. This is due to the lack of the
      typically antiparallel dimer arrangements, which often prevent the formation of
      strong aurophilic interactions. Furthermore, this polymorph shows
      hypsochromically shifted luminescence mechanochromism.

PMID- 30225511
TI  - Synthesis of difluoromethylated enynes by the reaction of alpha
      (trifluoromethyl)styrenes with terminal alkynes.
AB  - A novel and efficient method for the synthesis of difluoromethylated enynes by
      the reaction of alpha-(trifluoromethyl)styrenes with terminal alkynes with the
      assistance of NaOtBu was described. The mechanism of the reaction might involve
      the SN2' reaction of alpha-(trifluoromethyl)styrenes and a subsequent 1,3-H
      shift. Isomerization (E -> Z) of 1-difluoromethyl-1,3-enynes in the presence of
      ZrCl4 was also developed.

PMID- 30225512
TI  - Aggregation-induced near-infrared emitting platinum(ii) terpyridyl complex:
      cellular characterisation and lysosome-specific localisation.
AB  - A novel near-infrared luminogen (TPE/TPY-Pt-PA/PEG) based on the terpyridyl
      Pt(ii) complex with a tetraphenylethene periphery is synthesised and
      characterised. It displays aggregation-induced emission with the formation of
      self-assembled nanostructures. The nanoparticles fabricated with TPE/TPY-Pt
      PA/PEG show excellent biocompatibility with high specificity to lysosomes in HeLa
      cells.

PMID- 30225513
TI  - Self-reported health problems and prioritized goals in community-dwelling
      individuals with spinal cord injury in Sweden.
AB  - OBJECTIVE: To explore self-reported health problems and functional goals in
      community-dwelling individuals with spinal cord injury in Sweden. DESIGN: Cross
      sectional descriptive study that used a survey designed by an experienced peer
      mentor with spinal cord injury. SUBJECTS: Community-dwelling individuals with
      spinal cord injury from Sweden. METHODS: The survey was distributed online by the
      community peer-based organization RG Active Rehabilitation. RESULTS: A total of
      203 individuals (55% males, 90% acquired spinal cord injury) from all regions in
      Sweden completed the survey. Of these, 33% reported living with > 2 unbearable
      physical or psychological problems. While some problems (e.g. problems related to
      bladder and balance) were consistently ranked to be common across all years since
      injury and type of spinal cord injury, distribution of some other unbearable
      problems (e.g. type of pain, excessive weight) varied between subgroups. Years
      since injury, level of acquired spinal cord injury and sex, but not age-group or
      type of spinal cord injury, explained some of the variation in the goals.
      CONCLUSION: The high proportion of reported "unbearable" problems point to the
      stronger need for systematic, comprehensive, life-long, multi-disciplinary follow
      up for people with spinal cord injury. The high rate of goals related to
      improving strength and fitness across all participants independently of their
      characteristics highlight the important role of community organizations that
      offer such lifetime services.

PMID- 30225514
TI  - Environmental barriers, functioning and quality of life in 2008 Wenchuan
      earthquake victims with spinal cord injury eight years after the disaster: A
      cross-sectional study.
AB  - OBJECTIVE: To examine environmental barriers, func-tioning, and quality of life
      in Wenchuan earthquake survivors with spinal cord injury. DESIGN: Cross-sectional
      study. SUBJECTS: Thirty-two adult Wenchuan earthquake survivors with spinal cord
      injury. METHODS: Data were collected on environmental factors with the Nottwil
      Environmental Factors Inventory Short Form (NEFI-SF), physical and mental
      functioning with the 36-item Short-Form Health Survey (SF-36), and quality of
      life with the World Health Organization Quality of Life-BREF (WHOQOL-BREF).
      Descriptive analysis of environmental barriers and comparisons of SF-36 and
      WHOQOL-BREF domain scores with normative data were performed. Variations in
      outcomes across demographic and lesion characteristics were examined using Mann
      Whitney U test. Associations of NEFI-SF with SF-36 and WHOQOL-BREF domain scores
      were explored using Spearman's correlation. RESULTS: Wenchuan earthquake
      survivors with spinal cord injury were affected by a large number of
      environmental barriers. Their functioning and quality of life were considerably
      reduced in comparison with respective reference populations. Neither
      environmental barriers nor functioning or quality of life varied systematically
      by demographic and lesion characteristics. Increased numbers of perceived
      environmental barriers were strongly associated with decreased scores across SF
      36 and WHOQOL-BREF sub-domains. CONCLUSION: Wenchuan earthquake survivors with
      SCI faced a considerable number of environmental barriers and showed decreased
      functioning and quality of life. Environmental barriers were strongly related to
      functioning and quality of life.

PMID- 30225515
TI  - [Geriatric assessment in urology].
AB  - The geriatric patient is characterized by his age, multimorbidity, and
      multimedication. This results in a particular vulnerability, which requires
      "geriatric" methods, also in urology. Modern urology is dominated by prescriptive
      laboratory values, imaging features, or histologic results. However, this does
      not comply with the requirements of the geriatric patient, with his functional
      deficits, abilities, capabilities, and skills. In this context, screening methods
      provide the possibility to identify such patients. Reliable and valid precisely
      targeted assessments make it possible to detect these functional deficits. Basic
      assessments analyze typical problem areas of geriatric patients, such as
      mobility, autonomy, urinary incontinence, activities of daily life, cognition,
      and others. Additional assessments are used in cases of special issues such as
      depression or malnutrition.

PMID- 30225516
TI  - Central Nervous System Tuberculosis : Etiology, Clinical Manifestations and
      Neuroradiological Features.
AB  - PURPOSE: As a result of multilateral migration and globalization in times of
      humanitarian crises, western countries face a possible increase in the incidence
      of central nervous system tuberculosis (CNS TB). The diagnosis of CNS TB is
      challenging and often delayed due to the manifold and often non-specific
      presentation of the disease. The aim of this review is to analyze and summarize
      imaging features and correlated clinical findings of CNS TB. METHODS: The
      different manifestations of CNS TB are explained and illustrated by
      characteristic neuroradiological as well as neuropathological findings. An
      overview on diagnostic and therapeutic approaches is provided. For clarity,
      tables summarizing the lesion patterns, differential diagnoses and diagnostic
      hints are added. RESULTS: The CNS TB can be manifested (1) diffuse as tuberculous
      meningitis (TBM), (2) localized as tuberculoma or (3) tuberculous abscess or (4)
      in extradural and intradural spinal infections. Information on clinical
      presentation, underlying pathology and the distinguishing features is
      demonstrated. The TBM is further described, which may lead to cranial nerve
      palsy, hydrocephalus and infarction due to associated arteritis of the basal
      perforators. The differential diagnoses are vast and include other infections,
      such as bacterial, viral or fungal meningoencephalitis, malignant causes or
      systemic inflammation with CNS. Complicating factors of diagnosis and treatment
      are HIV coinfection, multi-drug resistance and TB-associated immune
      reconstitution inflammatory syndrome (IRIS). CONCLUSIONS: Neurologists and (neuro
      )radiologists should be familiar with the neuroradiological presentation and the
      clinical course of CNS TB to ensure timely diagnosis and treatment.

PMID- 30225517
TI  - Evolutionarily conserved coding properties favour the neuronal representation of
      heterospecific signals of a sympatric katydid species.
AB  - To function as a mechanism in premating isolation, the divergent and species
      specific calling songs of acoustic insects must be reliably processed by the
      afferent auditory pathway of receivers. Here, we analysed the responses of
      interneurons in a katydid species that uses long-lasting acoustic trills and
      compared these with previously reported data for homologous interneurons of a
      sympatric species that uses short chirps as acoustic signals. Some interneurons
      of the trilling species respond exclusively to the heterospecific chirp due to
      selective, low-frequency tuning and "novelty detection". These properties have
      been considered as evolutionary adaptations in the sensory system of the chirper,
      which allow it to detect signals effectively during the simultaneous calling of
      the sympatric sibling species. We propose that these two mechanisms, shared by
      the interneurons of both species, did not evolve in the chirper to guarantee its
      ability to detect the chirp under masking conditions. Instead we suggest that
      chirpers evolved an additional, 2-kHz component in their song and exploited pre
      existing neuronal properties for detecting their song under masking noise. The
      failure of some interneurons to respond to the conspecific song in trillers does
      not prevent intraspecific communication, as other interneurons respond to the
      trill.

PMID- 30225518
TI  - Response of rainbow trout's (Oncorhynchus mykiss) hypothalamus to glucose and
      oleate assessed through transcription factors BSX, ChREBP, CREB, and FoxO1.
AB  - We aimed to obtain information regarding mechanisms that link glucose- and fatty
      acid-sensing systems to expression of neuropeptides that regulate food intake in
      the fish brain. We assessed the relative expression and protein levels of the
      transcription factors BSX, ChREBP, FoxO1, and CREB in the hypothalamus of rainbow
      trout (Oncorhynchus mykiss) treated for 6 h with either glucose or oleate in vivo
      (intra-cerebroventricular treatment with 1 ul 100 g- 1 body weight of 40 ug
      glucose or 1 umol oleate) or in vitro (incubation with 4-8 mM glucose or 100-500
      uM oleate). BSX levels decreased after oleate treatment for mRNA (10% in vitro
      and 47% in vivo) and protein (25%), while minor changes occurred after glucose
      treatment. CREB values generally decreased after glucose or oleate treatment for
      mRNA (50% in vivo) as well as the phosphorylation status of protein (80%). Foxo1
      mRNA levels increased in vivo with glucose (129%) and decreased in vivo with
      oleate (60%), and protein phosphorylation status increased with glucose (in vivo)
      and oleate. mRNA values of chrebpalpha decreased in response to glucose and
      oleate, while protein levels decreased with oleate and increased with glucose.
      The results support the association of several transcription factors with
      metabolic control of food intake in fish.

PMID- 30225519
TI  - The fecal virome of red-crowned cranes.
AB  - The red-crowned crane is one of the rarest crane species, and its population is
      decreasing due to loss of habitat, poisoning, and infections. Using a viral
      metagenomics approach, we analyzed the virome of feces from wild and captive red
      crowned cranes, which were pooled separately. Vertebrate viruses belonging to the
      families Picornaviridae, Parvoviridae, Circoviridae, and Caliciviridae were
      detected. Among the members of the family Picornaviridae, we found three that
      appear to represent new genera. Six nearly complete genomes from members of the
      family Parvoviridae were also obtained, including four new members of the
      proposed genus "Chapparvovirus", and two members of the genus Aveparvovirus. Six
      small circular DNA genomes were also characterized. One nearly complete genome
      showing a low level of sequence identity to caliciviruses was also characterized.
      Numerous viruses believed to infect insects, plants, and crustaceans were also
      identified, which were probably derived from the diet of red-crowned cranes. This
      study increases our understanding of the enteric virome of red-crowned cranes and
      provides a baseline for comparison to those of other birds or following disease
      outbreaks.

PMID- 30225520
TI  - Spatial distribution of orally administered viral fusolin protein in the insect
      midgut and possible synergism between fusolin and digestive proteases to disrupt
      the midgut peritrophic matrix.
AB  - Oral inoculation of entomopoxvirus spindles, microstructures composed of fusolin
      protein, causes disruption of the peritrophic matrix (PM), a physical barrier
      against microbe infection, in the insect midgut. Although the atomic structure of
      fusolin has been determined, little has been directly elucidated of the mechanism
      of disruption of the PM. In the present study, we first performed an
      immunohistochemical examination to determine whether fusolin acts on the PM
      directly or indirectly in the midgut of Bombyx mori larvae that were inoculated
      with spindles of Anomala cuprea entomopoxvirus. This revealed that the PM, rather
      than the midgut cells, was the attachment site for fusolin. Fusolin broadly
      attached to the PM from the anterior to the posterior region, both to its
      ectoperitrophic and endoperitrophic surfaces and within the PM. These results
      likely explain why the whole of the PM is rapidly disintegrated. Second, we
      administered protease inhibitors mixed with spindles and observed decreased
      midgut protease activity and reduced disruption of the PM. This suggests that
      midgut protease(s) is also positively involved in PM disruption. Based on the
      present results, we propose an overall mechanism for the disruption of the PM by
      administration of fusolin.

PMID- 30225521
TI  - Molecular characterization of a novel citrivirus from citrus using next
      generation sequencing.
AB  - A novel positive-strand RNA virus infecting citrus with the tentative name
      "citrus leaf blotch virus 2" (CLBV-2), was identified in the present work. The
      complete genome sequence of CLBV-2 comprises 8,697 nucleotides (nt) excluding a
      poly(A) tail and three open reading frames (ORFs), showing the highest nucleotide
      sequence identity with the Actinidia strain (JN983456) of citrus leaf blotch
      virus (CLBV). The putative movement protein (ORF2), coat protein (ORF3), and 3'
      untranslated region (UTR) shared high sequence similarity with those of the
      extant CLBV isolates. In contrast, only low sequence similarity was observed in
      the 5' UTR and putative replicase polyprotein (ORF1) regions. The distant
      phylogenetic relationship between CLBV-2 and CLBV was deduced based on whole
      genome nucleotide and whole-ORF1 amino acid sequence comparisons. Sequence
      comparisons suggest that CLBV-2 acquired an ORF2-ORF3-3' UTR region homologous to
      CLBV by recombination with of an unknown citrivirus. In view of the fact that
      this genomic recombination event appears to have occurred between members of
      different species in the genus Citrivirus, we propose that CLBV-2 should be
      considered a member of a distinct species.

PMID- 30225522
TI  - Intranasal immunization of guinea pig with trivalent influenza antigen adjuvanted
      by Cyclamen europaeum tubers extract.
AB  - Cyclamen europaeum tubers extract (CTE) with concentration commonly used for
      human rhinosinusitis treatment was tested as mucosal adjuvant in experimental
      intranasal immunization of guinea pigs with concentrated commercially available
      influenza trivalent vaccine and subsequent infection with influenza strain
      A/California/04/2009 H1N1pdm. Dual intranasal immunization with vaccine compound
      consisting of 7.5 ug of each hemagglutinin and 500 ug of CTE in 50 ul induced
      reciprocal GMT on day 21 after immunization 40 (5-640) against H1N1pdm; 43.20 (5
      1280) against H3N2; 10.80 (5-80) against influenza B. Animals with HI titers 1/80
      against cell-derived antigen were completely protected against challenge with
      A/California/04/2009 H1N1pdm09.

PMID- 30225526
TI  - [Wishes of nursing home residents for their dying].
AB  - BACKGROUND: Institutions of inpatient geriatric care are dependent on specific
      and practicable concepts for the terminal care of old people, because residential
      and nursing homes are places for the last phase of life. OBJECTIVE: The objective
      of this study was to identify the wishes of residents for their dying who live in
      a residential or nursing home. METHOD: The analysis was based on 10 semi
      structured expert interviews with residential and nursing home residents. The
      interviews were evaluated using the method of qualitative summarizing content
      analysis. Based on the grounded theory a procedure was selected in which data
      were collected, prepared and evaluated in parallel. RESULTS AND DISCUSSION:
      Residents expressed, inter alia, the following wishes: not to receive life
      prolonging measures, not to have pain, not to be in need of care or bedridden, to
      receive affection while dying and to find forgiveness and reconciliation as well
      as to die peacefully in the residential and/or nursing home. In addition, there
      were a variety of wishes, which, due to their diversity make a unified approach
      to the palliative care of older people in residential and/or nursing homes
      impractical. The study showed that residents are thinking about dying and/or
      death, have desires for their dying and are also willing to talk about it. The
      recording and the translation of these wishes and also the response to the
      residents' fears can be achieved by the implementation of a palliative culture
      and the training of employees.

PMID- 30225524
TI  - The impact of maternal gestational weight gain on cardiometabolic risk factors in
      children.
AB  - AIMS/HYPOTHESIS: Accumulating evidence suggests an impact of gestational weight
      gain (GWG) on pregnancy outcomes; however, data on cardiometabolic risk factors
      later in life have not been comprehensively studied. This study aimed to evaluate
      the relationship between GWG and cardiometabolic risk in offspring aged 7 years.
      METHODS: We included a total of 905 mother-child pairs who enrolled in the follow
      up visit of the multicentre Hyperglycemia and Adverse Pregnancy Outcome study, at
      the Hong Kong Centre. Women were classified as having gained weight below, within
      or exceeding the 2009 Institute of Medicine (IOM) guidelines. A standardised GWG
      according to pre-pregnancy BMI categories was calculated to explore for any
      quadratic relationship. RESULTS: Independent of pre-pregnancy BMI, gestational
      hyperglycaemia and other confounders, women who gained more weight than the IOM
      recommendations had offspring with a larger body size and increased odds of
      adiposity, hypertension and insulin resistance (range of p values of all the
      traits: 4.6 * 10-9 < p < 0.0390) than women who were within the recommended range
      of weight gain during pregnancy. Meanwhile, women who gained less weight than
      outlined in the recommendations had offspring with increased risks of
      hypertension and insulin resistance, compared with those who gained weight within
      the recommended range (7.9 * 10-3 < p < 0.0477). Quadratic relationships for
      diastolic blood pressure, AUC for insulin, pancreatic beta cell function and
      insulin sensitivity index were confirmed in the analysis of standardised GWG (1.4
      * 10-3 < pquadratic < 0.0282). Further adjustment for current BMI noticeably
      attenuated the observed associations. CONCLUSIONS/INTERPRETATION: Both excessive
      and inadequate GWG have independent and significant impacts on childhood
      adiposity, hypertension and insulin resistance. Our findings support the notion
      that adverse intrauterine exposures are associated with persistent
      cardiometabolic risk in the offspring.

PMID- 30225527
TI  - [Journal Club].

PMID- 30225523
TI  - Streptococcal toxic shock syndrome in the intensive care unit.
AB  - The streptococcal toxic shock syndrome is a severe complication associated with
      invasive infections by group A streptococci. In spite of medical progresses in
      the care of patients with septic shock during the last decades, this condition
      has remained associated with a high mortality. Early recognition and
      multidisciplinary management are key to the care of patients with streptococcal
      toxic shock syndrome, with intensive and appropriate intensive support of failing
      organs, rapid diagnosis of infectious source(s), and surgical management. The
      epidemiology and risk factors for streptococcal toxic shock syndrome remain to be
      better studied, including the possible causal role of exposure to nonsteroidal
      anti-inflammatory drugs. In this review article, the authors review the current
      knowledge of streptococcal toxic shock syndrome and discuss the pathophysiology
      as well as its supportive and specific treatment.

PMID- 30225528
TI  - The association between the degree of nausea in pregnancy and subsequent
      posttraumatic stress.
AB  - Hyperemesis gravidarum (HG) is a pregnancy condition characterised by severe
      nausea and vomiting during early pregnancy. The experience of HG is for many
      women a traumatic event. Few studies have investigated a possible association
      between HG and birth-related posttraumatic stress. The objective of the current
      study was to assess whether HG increases the risk of birth-related posttraumatic
      stress symptoms (PTSS). This was a population-based pregnancy cohort study using
      data from the Akershus Birth Cohort Study (ABC study). A linear mixed model was
      used to estimate the association between the degree of nausea (no nausea (n =
      574), mild nausea (n = 813), severe nausea (n = 522) and HG (hospitalised due to
      nausea, n = 20)) and PTSS score at 8 weeks and 2 years after birth. At 8 weeks
      postpartum, women with HG had higher PTSS scores compared to women with no nausea
      (p = 0.008), women with mild nausea (p = 0.019) and women with severe nausea (p =
      0.027). After 2 years, women with HG had higher PTSS scores compared to women
      with no nausea (p = 0.038). Women with HG had higher PTSS scores following
      childbirth compared to women with less pronounced symptoms or no nausea at all.
      After 2 years, women with HG still had higher PTSS scores compared to women with
      no nausea. Although the overall differences in PTSS scores were small, the
      results may still be of clinical relevance.

PMID- 30225529
TI  - Prophylactic SSRI treatment for women suffering from mood and anxiety symptoms
      undergoing in vitro fertilization-a prospective placebo-controlled study.
AB  - To explore the mood protective effect of prophylactic SSRI treatment on women
      undergoing IVF suffering from moderate affective and anxiety symptoms. In a
      randomized double blind, placebo-controlled, parallel design study, 41 women
      diagnosed with an Adjustment Disorder, who were undergoing IVF treatments, were
      randomized into two groups; a study group (n = 22) administered escitalopram 10
      mg/day, and a control group (n = 19) administered placebo for a total of 8 weeks
      before and during the IVF treatment cycle. Patients were assessed at the onset of
      drug treatment and at embryo transfer. The main outcome measure was the
      difference in mean score severity rating of depression and anxiety symptoms on
      the CES-D and Zung questionnaires between groups at the time of embryo transfer.
      Secondary outcome measures included the MHI rating subscales addressing aspects
      of psychological distress and coping. At the day of embryo transfer (6 weeks of
      drug treatment), the CES-D average score for the treatment group was 6.40 (6.71)
      and 27.47 (4.29) on the Zung Self-Rating Anxiety Scale, while the placebo group
      scored an average of 15.83 (8.69) and 33.17 (6.95) receptively. These findings
      were significant (p = .004, p = .015 receptively) and were endorsed by the
      scoring on the MHI questionnaire subscales. Short-term treatment with SSRI may
      serve as a prophylactic treatment against the perpetuation and possible worsening
      of depressive and anxiety symptoms in women undergoing IVF treatments. Further
      studies concerning pharmacological interventions in larger samples and studies
      addressing screening for psychological stress indicators in this population are
      warranted.

PMID- 30225530
TI  - Administration of plasma-derived coagulation factor VIII during the perioperative
      period of mastectomy for breast cancer with acquired von Willebrand syndrome.
AB  - BACKGROUND: Acquired von Willebrand syndrome (aVWS) is a rare bleeding disorder
      with laboratory findings similar to those of congenital von Willebrand disease
      (VWD). Patients with aVWS may require prophylactic treatment to prevent excessive
      bleeding following surgery. To our knowledge, to date, there have been no reports
      on perioperative management for breast cancer patients with aVWS. CASE
      PRESENTATION: A 60-year-old woman with breast cancer was diagnosed with aVWS due
      to polycythemia vera. Pre-operative laboratory testing showed a high platelet
      count and low von Willebrand factor (VWF) activity. The VWF activity did not
      improve despite an attempt to suppress platelet count with hydroxyurea.
      Therefore, we decided to perioperatively supplement with plasma-derived factor
      VIII (FVIII) containing von Willebrand factor (FVIII/VWF concentrates) to perform
      curative surgery for breast cancer safely. Consequently, the patient did not
      develop hemorrhage during/after surgery and was discharged on postoperative day
      7, as planned, without problems. CONCLUSIONS: For a patient with aVWS, which
      carries a high risk of hemorrhage during the perioperative period, initiation of
      appropriate management like supplementation of FVIII/VWF concentrates might
      enable safe curative surgery for breast cancer, and collaboration with the
      hematology department is critical.

PMID- 30225531
TI  - Consolidated bioprocessing of lignocellulosic biomass to itaconic acid by
      metabolically engineering Neurospora crassa.
AB  - Neurospora crassa is a filamentous fungus potent in secreting cellulase and
      degrading lignocellulosic materials. Here, heterologous cis-aconitic acid
      decarboxylase was expressed in N. crassa to synthesize itaconic acid which is a
      high potential platform chemical with applications as an alternative for
      petroleum-based products. The present study demonstrated that itaconic acid can
      be produced directly from cellulose and other lignocellulosic materials by the
      engineered strain, with the highest production of 20.414 +/- 0.674 mg/L. The
      multivariate data analysis methods were used in the parameter analysis of the
      conversion process. It was found by the hot map analysis that itaconic acid
      production can promote the secretion of cellulase in N. crassa. Principal
      component analysis suggested that itaconic acid production was closely related to
      the concentration of the glucose degraded from lignocelluloses, indicating that
      the secretion of cellulase is key to the direct conversion of cellulose to
      itaconic acid in the engineered N. crassa. This work demonstrates that N. crassa
      could be considered as a new platform in the application of cellulose conversion
      to itaconic acid.

PMID- 30225533
TI  - Left atrial appendage-beyond being a thrombus-spreading tiger.

PMID- 30225532
TI  - [Navigated liver surgery : Current state and importance in the future].
AB  - The preoperative computer-assisted resection planning is the basis for every
      navigation. Thanks to modern algorithms, the prerequisites have been created to
      carry out a virtual resection planning and a risk analysis. Thus, individual
      segment resections can be precisely planned in any conceivable combination. The
      transfer of planning information and resection suggestions to the operating
      theater is still problematic. The so-called stereotactic liver navigation
      supports the exact intraoperative implementation of the planned resection
      strategy and provides the surgeon with real-time three-dimensional information on
      resection margins and critical structures during the resection. This is made
      possible by a surgical navigation system that measures the position of surgical
      instruments and then presents them together with the preoperative surgical
      planning data. Although surgical navigation systems have been indispensable in
      neurosurgery and spinal surgery for many years, these procedures have not yet
      become established as standard in liver surgery. This is mainly due to the
      technical challenge of navigating a moving organ. As the liver is constantly
      moving and deforming during surgery due to respiration and surgical manipulation,
      the surgical navigation system must be able to measure these alterations in order
      to adapt the preoperative navigation data to the current situation. Despite these
      advances, further developments are required until navigated liver resection
      enters clinical routine; however, it is already clear that laparoscopic liver
      surgery and robotic surgery will benefit most from navigation technology.

PMID- 30225534
TI  - Protein phosphatases of Saccharomyces cerevisiae.
AB  - The phosphorylation status of a protein is highly regulated and is determined by
      the opposing activities of protein kinases and protein phosphatases within the
      cell. While much is known about the protein kinases found in Saccharomyces
      cerevisiae, the protein phosphatases are much less characterized. Of the 127
      protein kinases in yeast, over 90% are in the same evolutionary lineage. In
      contrast, protein phosphatases are fewer in number (only 43 have been identified
      in yeast) and comprise multiple, distinct evolutionary lineages. Here we review
      the protein phosphatase families of yeast with regard to structure, catalytic
      mechanism, regulation, and signal transduction participation.

PMID- 30225535
TI  - Contact Dermatitis in Atopic Dermatitis Children-Past, Present, and Future.
AB  - Allergic contact dermatitis (ACD) used to be considered a rarity in children, but
      recently has been estimated to effect 4.4 million children in the USA alone, with
      a notable rise in investigative research in the field of pediatric ACD.
      Researchers have shown that patch testing is safe and effective in afflicted
      children and that those with atopic dermatitis (AD) have similar sensitization
      rates, although they have a higher sensitization to certain allergens, thought to
      be related to the inflammatory (IL-4) milieu. Patch testing assessment guidelines
      in children include five key considerations: if a patient's dermatitis worsens,
      changes distribution, fails to improve with topical therapy, or immediately
      rebounds after removal of topical treatments; if a patient has a particular
      distribution of dermatitis; if a working patient has hand eczema that fails to
      improve with therapy; if the patient has AD that started in adolescence or
      adulthood with definitely no history of childhood eczema; and importantly, if a
      patient has severe or widespread atopic dermatitis that will require
      immunosuppressive systemic medication.

PMID- 30225536
TI  - Validation and cross-cultural adaptation of the Korean version of the Core
      Outcome Measures Index in patients with degenerative lumbar disease.
AB  - PURPOSE: To translate and cross-culturally adapt the Core Outcome Measures Index
      (COMI) into the Korean language and to test the psychometric properties of the
      Korean COMI in patients with degenerative lumbar spine diseases. METHODS: A cross
      cultural adaptation of the COMI into Korean was carried out using established
      guidelines. A total of 117 patients with lumbar spinal diseases were recruited
      from the spinal center of a tertiary care teaching institution and completed a
      baseline questionnaire including the newly translated COMI, the visual analog
      scale for back pain and for leg pain, the Oswestry Disability Index (ODI), and
      the EuroQOL-5 dimensions (EQ-5D). Within 2 weeks after the first assessment, 83
      (71%) completed a second COMI questionnaire and a transition question (no change,
      slight change, moderate change, a lot of change) by phone to assess
      reproducibility. RESULTS: COMI summary scores displayed 1.7% floor effects and no
      ceiling effect. For construct validity, each COMI item and COMI summary score
      well correlated with its corresponding reference questionnaire. Therefore, the
      predefined hypotheses for the construct validities of each COMI item (rho > 0.4
      with the corresponding questionnaire) and the COMI summary score (rho > 0.6 with
      both ODI and EQ-5D) were confirmed. Intraclass correlation coefficients of each
      COMI item and summary score ranged from 0.93 to 0.98. Therefore, the hypothesis
      for reliability (ICC > 0.8) was confirmed. CONCLUSIONS: The present study
      highlights that the Korean version of the COMI is a reliable and valid outcome
      tool for use in Korean-speaking patients with degenerative lumbar spinal disease.
      These slides can be retrieved under Electronic Supplementary Material.

PMID- 30225537
TI  - The Association Between Training Load and Performance in Team Sports: A
      Systematic Review.
AB  - BACKGROUND: Adequate training loads promote favorable physical and physiological
      adaptations, reduce the likelihood of illness and injury, and, therefore,
      increase the possibility of success during competition. OBJECTIVES: Our objective
      was to systematically examine the association between training load and
      performance outcomes in team sports. METHODS: We systematically searched the
      PubMed, SPORTDiscus, and PsycINFO databases for original research published
      before July 2018. The search included terms relevant to training load,
      performance, and team sports. Articles were screened using pre-defined selection
      criteria, and methodological quality was assessed independently by two authors
      before data were extracted by the lead author. RESULTS: The electronic search
      yielded 5848 articles, 2373 of which were duplicates. A further 17 articles were
      retrieved from additional sources. In total, 26 articles met the inclusion
      criteria for this review, with quality scores ranging from 6 to 10 out of 11.
      Training exposure was more strongly associated with aerobic performance than
      other external training load measures. High-intensity activity (>= 90% of maximum
      heart rate) was strongly associated with aerobic performance. The individualized
      training impulse model was strongly associated with aerobic performance, whereas
      various other training impulse models and perceptual training load measures
      showed weak associations with aerobic performance. There were no clear
      associations between training load and neuromuscular variables or game-related
      statistics. CONCLUSION: We found no consistent associations between external
      training load measures and performance. High-intensity internal training load
      appears to be the most prominent indicator of aerobic performance.

PMID- 30225538
TI  - A novel Rice QTL qOPW11 Associated with Panicle Weight Affects Panicle and Plant
      Architecture.
AB  - BACKGROUND: The improvement of rice yield is a crucial global issue, but
      evaluating yield requires substantial efforts. Rice yield comprises the following
      indices: panicle number (PN), grain number per panicle (GN), 1000-grain weight,
      and percentage of ripened grain. To simplify measurements, we analyzed one
      panicle weight (OPW) as a simplified yield index that integrates GN, grain
      weight, and percentage of ripened grain, and verified its suitability as a proxy
      for GN and grain weight in particular. RESULTS: Quantitative trait locus (QTL)
      analysis using 190 recombinant inbred lines derived from Koshihikari (large
      panicle and small grain) and Yamadanishiki (small panicle and large grain),
      japonica cultivars detected three QTLs on chromosomes 5 (qOPW5), 7 (qOPW7) and 11
      (qOPW11). Of these, qOPW5 and qOPW11 were detected over two years. qOPW5 and
      qOPW7 increased OPW, and qOPW11 decreased it at Yamadanishiki alleles. A
      chromosome segment substitution line (CSSL) with a genomic segment from
      Yamadanishiki substituted in the Koshihikari genetic background harboring qOPW5
      increased grain weight. qOPW11 had the largest genetic effect of QTLs, which was
      validated using a CSSL. Substitution mapping using four CSSLs revealed that
      qOPW11 was located in the range of 1.46 Mb on chromosome 11. The CSSL harboring
      qOPW11 decreased primary and secondary branch numbers, culm length, and panicle
      length, and increased PN. CONCLUSIONS: In this study, three QTLs associated with
      OPW were detected. The CSSL with the novel and largest QTL, qOPW11, differed in
      some traits associated with both panicle and plant architecture, indicating
      different functions for the meristem in the vegetative versus the reproductive
      stages. qOPW5 coincided with an identified QTL for grain width and grain weight,
      suggesting that qOPW5 was affected by rice grain size. OPW can be considered a
      useful trait for efficient detection of QTLs associated with rice yield.

PMID- 30225539
TI  - Presence and activity of HPV in primary lung cancer.
AB  - PURPOSE: Evaluate the presence of human papillomavirus (HPV) in biopsies of
      Brazilian patients with lung cancer and also the expression of the E6 and E7
      oncoproteins. HPV is widely known as an important condition for cervical cancer
      although evidence today shows it is associated with several other types of cancer
      and may also be involved in lung cancer development. However, there are some
      divergences regarding the presence and activity of HPV in lung carcinogenesis.
      METHODS: The detection of HPV was performed by PCR, followed by genotype and
      immunohistochemical evaluation of E6 and E7 HPV type specific, from 63 patients.
      RESULTS: HPV was found to be present in 33 of the 63 samples, and types 16 and 18
      were detected with frequencies of 81% (27/33) and 19% (6/33), respectively. About
      the presence of the virus in different histological types of tumors, HPV was
      detected in squamous cell carcinoma (39.39%), followed by adenocarcinoma (33.33%)
      and small cell carcinoma (18.18%) and large cell carcinoma (9.1%). The presence
      of the E6 (antibody anti-HPV 16 and anti-HPV 18) and E7 (antibody anti-HPV 16 and
      anti-HPV 18) oncoproteins was detected by immunohistochemical stain technique in
      28/33 samples and 25/33 samples, respectively. CONCLUSIONS: Our results suggest
      that the lung tumor patients have high prevalence of HPV and the virus is not
      only present but also active in tumor cells. Therefore, the HPV is probably
      playing a role in lung carcinogenesis.

PMID- 30225540
TI  - Circulating microRNA-99 family as liquid biopsy marker in pancreatic
      adenocarcinoma.
AB  - PURPOSE: Recently, we identified the microRNA-99 family as unfavorable prognostic
      factor in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this
      study is to evaluate its value as circulating biomarker for PDAC. METHODS: Tissue
      and corresponding preoperative blood samples of 181 patients with PDAC UICC
      Stages I-IV (n = 90), intraductal papillary mucinous neoplasm (IPMN, n = 11),
      chronic pancreatitis (n = 40), pancreatic cystadenoma (n = 20), and age-matched
      healthy blood serum controls (n = 20) were collected between 2014 and 2017
      prospectively. Expression of microRNA-21 as confirmatory marker and the microRNA
      99 family, consisting of microRNA-99a, -99b, and -100, was analyzed by qRT-PCR.
      Target analysis of insulin-like growth factor 1 receptor (IGF1R) was performed
      using tissue array immunohistochemistry and Western blotting. RESULTS: Expression
      of microRNA-99 family members was significantly increased in macrodissected tumor
      tissue and corresponding blood serum samples (p < 0.05) of patients with PDAC of
      all stages. Correspondingly, its target protein IGF1R was upregulated (p < 0.001)
      in carcinoma tissue. Circulating and tissue-related microRNA-100 could well
      discriminate PDAC from healthy samples with area under the receiver operating
      characteristic (ROC) curve (AUC) values of 0.81 and 0.85, respectively. Low
      expression of circulating microRNA-100 was associated with significantly improved
      overall survival (p = 0.004) and recurrence-free survival (p = 0.03) in
      multivariate analyses. Circulating microRNA-21 was overexpressed in PDAC with
      fair discrimination between PDAC and healthy controls (AUC = 0.71) and decreased
      overall survival (p = 0.046) and recurrence-free survival (p = 0.03) in PDAC
      patients. CONCLUSIONS: Multivariate survival and ROC analyses identified
      circulating microRNA-100 as potential diagnostic and prognostic marker in PDAC
      patients.

PMID- 30225542
TI  - Simulation of schoolyard's microclimate and human thermal comfort under
      Mediterranean climate conditions: effects of trees and green structures.
AB  - The present study explores the effects on microclimate parameters and on heat
      stress conditions of the bioclimatic redevelopment of an urban schoolyard based
      mainly on inserting shading canopies and replacing hard surfaces with green
      cover. This included the use of the recent version of the microclimate model ENVI
      met (V4), first validated using experimental data and then later applied to
      different case studies in schoolgrounds of Volos, a coastal city in central
      Greece under Mediterranean type climate. The simulation of the existing yard
      condition showed that the values of the biometorological index PET
      (physiologically equivalent temperature, in  degrees C), were within the range of
      the thermal sensation class of extreme heat stress (> 41  degrees C) from early
      morning, while at midday 80.5% of the yard area was within the range of the above
      class. With the implementation of the redesign proposal, 69.9% of the yard area
      was improved by two or three PET scale classes, helping to improve the
      microclimate in 82% of the total area of the courtyard. Tree canopies reduced the
      direct incident radiation more than 90%, reduced Tmrt and PET index up to 31 
      degrees C and 19  degrees C, respectively, and the surface ground temperatures of
      wet grass and hard surfaces more than 20  degrees C and 14  degrees C,
      respectively.

PMID- 30225541
TI  - MicroRNA-338-5p plays a tumor suppressor role in glioma through inhibition of the
      MAPK-signaling pathway by binding to FOXD1.
AB  - PURPOSE: MicroRNAs (miRs) play an important role in many cancers and can affect
      cancer cell behavior, including glioma. This study aims at investigating the
      effects of miR-338-5p on the senescence, migration, invasion, and apoptosis of
      glioma cells via MAPK-signaling pathway by binding to FOXD1. METHODS: Gene
      expression microarray analysis was performed to screen differentially expressed
      miRNAs associated with glioma. Glioma tissues and adjacent tissues were
      collected. siRNA, mimic, and inhibitor were introduced for investigating the
      tumor suppressor role of miR-338-5p in glioma. Proliferation, migration,
      invasion, senescence, cell-cycle distribution, and apoptosis after transfection
      were detected by MTT assay, scratch test, Transwell assay, beta-galactosidase
      staining, and flow cytometry, respectively. RESULTS: FOXD1 was identified as the
      up-regulated gene in glioma based on microarray data of GSE65626. FOXD1 was the
      target gene of miR-338-5p. Glioma tissues had increased expression of FOXD1, MEK
      2, ERK-1, DAF, PCNA, and Bcl-2, and decreased expression of miR-338-5p and Bax.
      In cell experiments, after transfected with overexpressed miR-338-5p, higher
      expression of miR-338-5p, Bax, CD133, ZEB1, SOX2, SNAI1, and MMP2, but lower
      expression of FOXD1, MEK-2, ERK-1, Bcl-2, DAF, and PCNA were found accompanied
      with weaker proliferation, migration and invasion as well as stemness abilities
      but stronger senescence and higher apoptosis rate. CONCLUSION: We found that
      overexpression of miR-338-5p suppresses glioma cell proliferation, migration, and
      invasion and accelerates its senescence and apoptosis by decreasing FOXD1
      expression via inhibition of activation of MAPK-signaling pathway.

PMID- 30225543
TI  - Actinomycetospora callitridis sp. nov., an endophytic actinobacterium isolated
      from the surface-sterilised root of an Australian native pine tree.
AB  - An endophytic actinobacterium, strain CAP 335T, was isolated from a root sample
      of a native pine tree growing on the Bedford Park campus of Flinders University,
      Adelaide, South Australia. The result of a polyphasic study showed that this
      strain was identified as a new member of the genus Actinomycetospora. This strain
      was observed to be a Gram stain-positive, aerobic actinobacterium with well
      developed substrate mycelia and to form short chains of spores. Actinomycetospora
      chibensis TT04-21T and Actinomycetospora straminea IY07-55T were found to be
      close phylogenetic neighbours, each sharing 99.1% 16S rRNA gene similarity.
      Chemotaxonomic data including major fatty acids, cell wall components and major
      menaquinones confirmed the affiliation of strain CAP 335T to the genus
      Actinomycetospora. The phylogenetic analysis, physiological and biochemical
      studies and DNA-DNA hybridization, allowed the genotypic and phenotypic
      differentiation of strain CAP 335T and the closely related species with valid
      names. The name proposed for the new species is Actinomycetospora callitridis sp.
      nov. The type strain is CAP 335T (= DSM 101857T = NRRL B-65350T).

PMID- 30225544
TI  - Streptomyces desertarenae sp. nov., a novel actinobacterium isolated from a
      desert sample.
AB  - A Streptomyces isolate, designated strain SYSU D8023T, was isolated from a desert
      sand sample collected from Gurbantunggut desert, China. The characterisation of
      the isolate was achieved using a polyphasic taxonomic approach. The isolate was
      found to be Gram-positive and aerobic. The strain was found to be able to grow at
      14-50  degrees C, pH 6.0-9.0 and in the presence of up to 7% (w/v) NaCl. Strain
      SYSU D8023T contains LL-diaminopimelic acid as a cell wall diamino acid. The
      polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, an
      unidentified glycolipid and an unidentified phospholipid. MK-9(H6) and MK-9(H8)
      were detected as the respiratory quinones, and anteiso-C15:0, iso-C16:0 and
      anteiso-C17:0 as the predominant fatty acids. Pairwise comparison of the 16S rRNA
      gene sequences indicated that strain SYSU D8023T has a sequence identity of 97.9%
      to Streptomyces barkulensis RC 1831T. The DNA G + C content of strain SYSU D8023T
      was determined to be 70.1 mol%. Based on the analyses of the phenotypic,
      genotypic and phylogenetic characteristics, strain SYSU D8023T was concluded to
      represent a novel species of the genus Streptomyces, for which the name
      Streptomyces desertarenae sp. nov. is proposed. The type strain of the species is
      SYSU D8023T (= CGMCC 4.7455T = KCTC 49023T).

PMID- 30225545
TI  - Expression and characterisation of a pH and salt tolerant, thermostable and
      xylose tolerant recombinant GH43 beta-xylosidase from Thermobifida halotolerans
      YIM 90462T for promoting hemicellulose degradation.
AB  - A gene encoding a beta-xylosidase (designated as Thxyl43A) was cloned from strain
      Thermobifida halotolerans YIM 90462T. The open reading frame of this gene encodes
      550 amino acid residues. The gene was over-expressed in Escherichia coli and the
      recombinant protein was purified. The monomeric Thxyl43A protein presented a
      molecular mass of 61.5 kDa. When p-nitrophenyl-beta-d-xylopyranoside was used as
      the substrate, recombinant Thxyl43A exhibited optimal activity at 55  degrees C
      and pH 4.0 to 7.0, being thermostable by maintaining 47% of its activity after 30
      h incubation at 55  degrees C. The recombinant enzyme retained more than 80%
      residual activity after incubation at pH range of 4.0 to 12.0 for 24 h,
      respectively, which indicated notable thermostability and pH stability of
      Thxyl43A. Moreover, Thxyl43A displayed high catalytic activity (> 60%) in
      presence of 5-35% NaCl (w/v) or 1-20% ionic liquid (w/v) or 1-50 mM xylose. These
      properties suggest that Thxyl43A has potential for promoting hemicellulose
      degradation and other industrial applications.

PMID- 30225546
TI  - Differentiating Disease Flare From Infection: A Common Problem in Rheumatology.
      Do 18F-FDG PET/CT Scans and Novel Biomarkers Hold The Answer?
AB  - PURPOSE OF REVIEW: Fever is common within rheumatology but it is often
      challenging to identify its source. To do so correctly is paramount in patients
      with an underlying inflammatory condition receiving immunosuppressive therapy.
      This review article looks at the available evidence and merits of both 18F-fluoro
      deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)
      scans and new proposed biomarkers in determining the cause of fever within
      rheumatology. RECENT FINDINGS: 18F-FDG PET/CT scans are already an established
      tool in the detection and diagnosis of malignancy and are emerging for use in
      fever of unknown origin. More recently, they have been used to identify
      rheumatological causes of fever such as large vessel vasculitis and adult-onset
      Still's disease. Within these conditions, biomarkers such as procalcitonin and
      presepsin may help to differentiate endogenous from exogenous pyrogens. 18F-FDG
      PET/CT scanning shows promise in locating the source of pyrogens and may be
      superior to other conventional forms of imaging. As evidence and test
      availability increases, its use is likely to become commonplace in the diagnostic
      work-up of fever. Once a source is located, selected biomarkers may be used to
      confirm a cause.

PMID- 30225548
TI  - But where did the centromeres go in the chicken genome models?
AB  - The chicken genome was the third vertebrate to be sequenced. To date, its
      sequence and feature annotations are used as the reference for avian models in
      genome sequencing projects developed on birds and other Sauropsida species, and
      in genetic studies of domesticated birds of economic and evolutionary biology
      interest. Therefore, an accurate description of this genome model is important to
      a wide number of scientists. Here, we review the location and features of a very
      basic element, the centromeres of chromosomes in the galGal5 genome model.
      Centromeres are elements that are not determined by their DNA sequence but by
      their epigenetic status, in particular by the accumulation of the histone-like
      protein CENP-A. Comparison of data from several public sources (primarily marker
      probes flanking centromeres using fluorescent in situ hybridization done on giant
      lampbrush chromosomes and CENP-A ChIP-seq datasets) with galGal5 annotations
      revealed that centromeres are likely inappropriately mapped in 9 of the 16
      galGal5 chromosome models in which they are described. Analysis of karyology data
      confirmed that the location of the main CENP-A peaks in chromosomes is the best
      means of locating the centromeres in 25 galGal5 chromosome models, the majority
      of which (16) are fully sequenced and assembled. This data re-analysis reaffirms
      that several sources of information should be examined to produce accurate genome
      annotations, particularly for basic structures such as centromeres that are
      epigenetically determined.

PMID- 30225547
TI  - Pharmacotherapy of premature ejaculation: a systematic review and network meta
      analysis.
AB  - PURPOSE: The purpose of the study was to conduct a systematic evaluation of the
      different general prescribed drugs for premature ejaculation (PE). METHODS: A
      systematic literature search of MEDLINE, Cochrane Central Register of Controlled
      Trials, and Web of Science for Systematic Reviews was performed on 1 March 2018.
      Intravaginal ejaculation latency time (IELT) was the main outcome. Analysis was
      performed under multivariate random-effects network model and efficacies of drugs
      were ranked with surface under the cumulative ranking (SUCRA) probabilities.
      RESULTS: A total of 48 studies were reviewed and 40 of them were further enrolled
      into network meta-analysis. The majority of RCTs were of unclear methodological
      quality. Pooled evidence suggested that topical anaesthetic creams (TAs),
      tramadol, selective serotonin reuptake inhibitors (SSRIs), and phosphodiesterase
      type 5 inhibitors (PDE5is) are more effective at prolonging IELT comparing with
      placebo. TAs (90%) on demand (OD) and PDE5is plus SSRI (89.8%) had the highest
      SUCRA, which meant the most probable to be the most effective intervention.
      CONCLUSIONS: We recommend the initial use of dapoxetine 30 mg OD for PE because
      it has been tested in largest and better designed clinical trials rather than it
      is more effective than the other drugs studied. TAs and tramadol 50 mg OD can be
      used as a viable alternative to oral treatment with SSRIs. PDE5is combined with
      SSRIs are more effective than SSRIs monotherapy but are also associated with more
      side effects. PDE5is OD can be recommended to PE patients with ED.

PMID- 30225550
TI  - A Nationwide Safety Analysis of Discharge on the First Postoperative Day After
      Bariatric Surgery in Selected Patients.
AB  - BACKGROUND: Enhanced recovery after surgery has led to early recovery and shorter
      hospital stay after laparoscopic Roux-en-Y gastric bypass (LRYGB) and
      laparoscopic sleeve gastrectomy (LSG). This study aims to assess feasibility and
      outcomes of postoperative day (POD) 1 discharge after LRYGB and LSG from the
      Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program
      (MBSAQIP) 2015 dataset. METHODS: Patients who underwent elective LRYGB and LSG
      and were discharged on POD 1 and 2 were extracted from the MBSAQIP dataset. A 1:1
      propensity score matching was performed between cases with POD 1 vs POD 2
      discharge, and the 30-day outcomes of the cohorts were compared. RESULTS: A total
      of 80,464 patients met the study criteria: 8862 LRYGB and 31,370 LSG cases, which
      were discharged on POD 1, and matched 1:1 with those discharged on POD 2. Within
      the LRYGB cohort, patients discharged on POD 2 had higher all-cause morbidity
      (7.5% vs 6.1%; p < 0.001) and 30-day re-intervention (2.0% vs 1.5%; p = 0.004) in
      comparison with patients discharged on POD 1. There were no statistical
      differences with respect to serious morbidity (0.5% vs 0.4%; p = 0.15), 30-day
      readmission (4.9% vs 4.5%; p = 0.2), and 30-day reoperation (1.3% vs 1.2%; p =
      0.7). Within the LSG cohort, patients discharged on POD 2 had higher all-cause
      morbidity (4.2% vs 3.4%; p < 0.001), serious morbidity (0.4% vs 0.3%; p < 0.001),
      30-day re-intervention (1.0% vs 0.6%; p < 0.001), and 30-day readmission (2.9% vs
      2.5%; p = 0.002) in comparison with patients discharged on POD 1. CONCLUSIONS:
      Early discharge on POD 1 may be safe in a selective group of bariatric patients
      without significant comorbidities.

PMID- 30225549
TI  - Independent and Combined Effects of Chronic HIV-Infection and Tobacco Smoking on
      Brain Microstructure.
AB  - HIV-infected individuals (HIV+) have 2-3 times higher prevalence of tobacco
      smoking than the general U.S. population. This study aims to evaluate the
      independent and combined effects of tobacco-smoking and HIV-infection on brain
      microstructure and cognition using a 2 * 2 design. 21 HIV + Smokers, 25 HIV +
      Nonsmokers, 25 Seronegative (SN)-Smokers and 23 SN-Nonsmokers were evaluated
      using diffusion tensor imaging. Fractional anisotropy (FA), mean (MD), radial
      (RD) and axial (AD) diffusivity were assessed in 8 major cerebral fiber tracts
      and 5 subcortical regions. Cognitive performance in 7 neurocognitive domains was
      also assessed. Compared to SN, HIV+ had higher AD in genu of corpus callosum
      (GCC, p = 0.002). Smokers also had higher diffusivities in GCC, splenium of
      corpus callosum (SCC), anterior corona radiata (ACR), sagittal stratum (SS) and
      superior fronto-occipital fasciculus (SFO), than Nonsmokers (p-values<0.001
      0.003). Tobacco-Smoking and HIV-infection showed synergistic effects on AD_SS (p
      = 0.002) and RD_SFO (p = 0.02), but opposite effects in FA_putamen (p = 0.024).
      Additive effects from HIV+ and Tobacco-Smoking were observed in 9 other white
      matter tracts, with highest diffusivities and lowest FA in HIV + Smokers. Higher
      diffusivities in the GCC, SCC, ACR and SS predicted poorer cognitive performance
      across all participants (p <= 0.001). Higher AD_GCC also predicted slower Speed
      of information processing and poorer Fluency and Attention only in HIV + Smokers
      (p = 0.001-0.003). Chronic tobacco smoking and HIV-infection appear to have
      additive and synergistic adverse effects on brain diffusivities, suggesting
      greater neuroinflammation, which may contribute to poorer cognition. Therefore,
      chronic tobacco-smoking may be a risk factor for HIV-associated neurocognitive
      disorders. Graphical Abstract ?.

PMID- 30225552
TI  - Acetazolamide Mitigates Intracranial Pressure Spikes Without Affecting Functional
      Outcome After Experimental Hemorrhagic Stroke.
AB  - Increased intracranial pressure (ICP) after stroke can lead to poor outcome and
      death. Novel treatments to combat ICP rises are needed. The carbonic anhydrase
      inhibitor acetazolamide diminishes cerebrospinal fluid (CSF) production, reduces
      ICP in healthy animals, and is beneficial for idiopathic intracranial
      hypertension patients. We tested whether acetazolamide mitigates ICP elevations
      by presumably decreasing CSF volume after collagenase-induced striatal hemorrhage
      in rats. We confirmed that acetazolamide did not adversely affect hematoma
      formation in this model or physiological variables, such as temperature. Then, we
      assessed the effects of acetazolamide on ICP. Lastly, we tested the effects of
      acetazolamide on behavioral and histological outcome. Acetazolamide reduced the
      magnitude and occurrence of short-timescale ICP spikes, assessed as
      disproportionate increases in ICP (sudden ICP increases > 10 mmHg), 1-min peak
      ICP, and the magnitude of spikes > 20 mmHg. However, mean ICP was unaffected. In
      addition, acetazolamide reduced ICP variability, reflecting improved intracranial
      compliance. Compliance measures were strongly correlated with high peak and mean
      ICP, whereas ipsilateral hemisphere water content was not correlated with ICP.
      Despite effects on ICP, acetazolamide did not improve behavioral function or
      affect lesion size. In summary, we show that intracerebral hemorrhage creates an
      impaired compliance state within the cranial space that can result in large,
      transient ICP spikes. Acetazolamide ameliorates intracranial compliance and
      mitigates ICP spikes, but does not improve functional outcome, at least for
      moderate-severity ICH in rats.

PMID- 30225551
TI  - Apolipoprotein E Exerts a Whole-Brain Protective Property by Promoting M1?
      Microglia Quiescence After Experimental Subarachnoid Hemorrhage in Mice.
AB  - Subarachnoid hemorrhage (SAH) is a neurologically destructive stroke in which
      early brain injury (EBI) plays a pivotal role in poor patient outcomes. Expanding
      upon our previous work, multiple techniques and methods were used in this
      preclinical study to further elucidate the mechanisms underlying the beneficial
      effects of apolipoprotein E (ApoE) against EBI after SAH in murine apolipoprotein
      E gene-knockout mice (Apoe-/-, KO) and wild-type mice (WT) on a C57BL/6J
      background. We reported that Apoe deficiency resulted in a more extensive EBI at
      48 h after SAH in mice demonstrated by MRI scanning and immunohistochemical
      staining and exhibited more extensive white matter injury and neuronal apoptosis
      than WT mice. These changes were associated with an increase in NADPH oxidase 2
      (NOX2) expression, an important regulator of both oxidative stress and
      inflammatory cytokines. Furthermore, immunohistochemical analysis revealed that
      NOX2 was abundantly expressed in activated M1 microglia. The JAK2/STAT3 signaling
      pathway, an upstream regulator of NOX2, was increased in WT mice and activated to
      an even greater extent in Apoe-/- mice; whereas, the JAK2-specific inhibitor,
      AG490, reduced NOX2 expression, oxidative stress, and inflammation in Apoe
      deficient mice. Also, apoE-mimetic peptide COG1410 suppressed the JAK2/STAT3
      signaling pathway and significantly reduced M1 microglia activation with
      subsequent attenuation of oxidative stress and inflammation after SAH. Taken
      together, apoE and apoE-mimetic peptide have whole-brain protective effects that
      may reduce EBI after SAH via M1 microglial quiescence through the attenuation of
      the JAK2/STAT3/NOX2 signaling pathway axis.

PMID- 30225553
TI  - Improving the performance of eye trackers with limited spatial accuracy and low
      sampling rates for reading analysis by heuristic fixation-to-word mapping.
AB  - The recent growth in low-cost eye-tracking systems makes it feasible to
      incorporate real-time measurement and analysis of eye position data into
      activities such as learning to read. It also enables field studies of reading
      behavior in the classroom and other learning environments. We present a study of
      the data quality provided by two remote eye trackers, one being a low-sampling
      rate, low-cost system. Then we present two algorithms for mapping fixations
      derived from the data to the words being read. One is for immediate (or real
      time) mapping of fixations to words and the other for deferred (or post hoc)
      mapping. Following this, an evaluation study is reported. Both studies were
      carried out in the classroom of a Finnish elementary school with students who
      were second graders. This study shows very high success rates in automatically
      mapping fixations to the lines of text being read when the mapping is deferred.
      The success rates for immediate mapping are comparable with those obtained in
      earlier studies, although here the data is collected some 10 min after initial
      calibration of low-sample (30 Hz) remote eye trackers, rather than a laboratory
      setting using high-sampling-rate trackers. The results provide a solid basis for
      developing systems for use in classrooms and other learning environments that can
      provide immediate automatic support with reading, and share data between a group
      of learners and the teacher of that group. This makes possible new approaches to
      the learning of reading and comprehension skills.

PMID- 30225554
TI  - Robotic-arm assisted total knee arthroplasty has a learning curve of seven cases
      for integration into the surgical workflow but no learning curve effect for
      accuracy of implant positioning.
AB  - PURPOSE: The primary objective of this study was to determine the surgical team's
      learning curve for robotic-arm assisted TKA through assessments of operative
      times, surgical team comfort levels, accuracy of implant positioning, limb
      alignment, and postoperative complications. Secondary objectives were to compare
      accuracy of implant positioning and limb alignment in conventional jig-based TKA
      versus robotic-arm assisted TKA. METHODS: This prospective cohort study included
      60 consecutive conventional jig-based TKAs followed by 60 consecutive robotic-arm
      assisted TKAs performed by a single surgeon. Independent observers recorded
      surrogate markers of the learning curve including operative times, stress levels
      amongst the surgical team using the state-trait anxiety inventory (STAI)
      questionnaire, accuracy of implant positioning, limb alignment, and complications
      within 30 days of surgery. Cumulative summation (CUSUM) analyses were used to
      assess learning curves for operative time and STAI scores in robotic TKA.
      RESULTS: Robotic-arm assisted TKA was associated with a learning curve of seven
      cases for operative times (p = 0.01) and surgical team anxiety levels (p = 0.02).
      Cumulative robotic experience did not affect accuracy of implant positioning
      (n.s.) limb alignment (n.s.) posterior condylar offset ratio (n.s.) posterior
      tibial slope (n.s.) and joint line restoration (n.s.). Robotic TKA improved
      accuracy of implant positioning (p < 0.001) and limb alignment (p < 0.001) with
      no additional risk of postoperative complications compared to conventional manual
      TKA. CONCLUSION: Implementation of robotic-arm assisted TKA led to increased
      operative times and heightened levels of anxiety amongst the surgical team for
      the initial seven cases but there was no learning curve for achieving the planned
      implant positioning. Robotic-arm assisted TKA improved accuracy of implant
      positioning and limb alignment compared to conventional jig-based TKA. The
      findings of this study will enable clinicians and healthcare professionals to
      better understand the impact of implementing robotic TKA on the surgical
      workflow, assist the safe integration of this procedure into surgical practice,
      and facilitate theatre planning and scheduling of operative cases during the
      learning phase. LEVEL OF EVIDENCE: II.

PMID- 30225555
TI  - Resource use and clinical outcomes in blunt thoracic injury: a 10-year trauma
      registry comparison between southern Finland and Germany.
AB  - PURPOSE: Serious thoracic injuries are associated with high mortality, morbidity,
      and costs. We compared patient populations, treatment, and survival of serious
      thoracic injuries in southern Finland and Germany. METHODS: Mortality, patient
      characteristics and treatment modalities were compared over time (2006-2015) in
      all patients with Abbreviated Injury Scale (AIS) thorax >= 3, Injury Severity
      Score (ISS) > 15, age > 15 years, blunt trauma mechanism, and treatment in
      Intensive Care Unit (ICU) in Level 1 hospitals included in the Helsinki Trauma
      Registry (HTR) and the TraumaRegister DGU(r) (TR-DGU). RESULTS: We included 934
      patients from HTR and 25 448 patients from TR-DGU. Pre-hospital differences were
      seen between HTR and TR-DGU; transportation in the presence of a physician in 61%
      vs. 97%, helicopter use in 2% vs. 42%, intubation in 31% vs. 55%, and
      thoracostomy in 6% vs. 10% of cases, respectively. The mean hospital length of
      stay (LOS) and ICU LOS was shorter in HTR vs. TR-DGU (13 vs. 25 days and 9 vs. 12
      days, respectively). Our main outcome measure, standardised mortality ratio, was
      not statistically significantly different [1.01, 95% confidence interval (CI)
      0.84-1.18; HTR and 0.97, 95% CI 0.94-1.00; TR-DGU]. CONCLUSIONS: Major
      differences were seen in pre-hospital resources and use of pre-hospital
      intubation and thoracostomy. In Germany, pre-hospital intubation, tube
      thoracostomy, and on-scene physicians were more prevalent, while patients stayed
      longer in ICU and in hospital compared to Finland. Despite these differences in
      resources and treatment modalities, the standardised mortality of these patients
      was not statistically different.

PMID- 30225556
TI  - Picomolar concentrations of oligomeric alpha-synuclein sensitizes TLR4 to play an
      initiating role in Parkinson's disease pathogenesis.
AB  - Despite the wealth of genomic and transcriptomic data in Parkinson's disease
      (PD), the initial molecular events are unknown. Using LD score regression
      analysis, we show significant enrichment in PD heritability within regulatory
      sites for LPS-activated monocytes and that TLR4 expression is highest within
      human substantia nigra, the most affected brain region, suggesting a role for
      TLR4 inflammatory responses. We then performed extended incubation of cells with
      physiological concentrations of small alpha-synuclein oligomers observing the
      development of a TLR4-dependent sensitized inflammatory response with time,
      including TNF-alpha production. ROS and cell death in primary neuronal cultures
      were significantly reduced by TLR4 antagonists revealing that an indirect
      inflammatory mechanism involving cytokines produced by glial cells makes a major
      contribution to neuronal death. Prolonged exposure to low levels of alpha
      synuclein oligomers sensitizes TLR4 responsiveness in astrocytes and microglial,
      explaining how they become pro-inflammatory, and may be an early causative event
      in PD.

PMID- 30225557
TI  - The cost incurred by victims of bullying from a societal perspective: estimates
      based on a German online survey of adolescents.
AB  - Being a victim of bullying is linked to various social, emotional and behavioral
      problems potentially leading to a reduced quality of life. Furthermore, victims
      of bullying may cause extensive costs for society, for example by an above
      average need for healthcare services. The present study was designed to quantify
      the costs and the loss of quality of life attributable to bullying by comparing
      victims with a control group of non-bullied students. A cross-sectional sample of
      1293 adolescents (mean age 14.07, SD = 1.36) and their parents reported on
      bullying victimization, quality of life (adolescents' self-report), and annual
      direct (medical and non-medical) as well as indirect costs (parents' self-report)
      from a societal perspective (all expressed in ?, year 2014 and 2015). For
      frequent (20.6% of our sample; costs: ?8461.80 p.a.) but not occasional (13.3%;
      costs: ?2850.06) bullying, victimization was associated with significantly higher
      costs compared to non-bullied adolescents (costs: ?3138.00; annual difference
      between frequently bullied students and controls: ?5323.01 p.a.; p = 0.008). Cost
      drivers included increased direct medical costs, but mostly indirect costs caused
      by productivity losses of the parents. Self-reported quality of life of frequent
      victims was considerably reduced (T = - 10.96; p < 0.001); also occasional
      bullying showed significantly reduced values in global quality of life (T = -
      5.73; p < 0.001). The present findings demonstrate that frequent bullying is
      associated with substantial cost to society and reduced quality of life of
      victims. This observation underscores the need for effective school-based
      bullying prevention and suggests a high potential of effective programs to be
      cost effective as well.

PMID- 30225558
TI  - Survival rate, causes of death, and risk factors in systemic sclerosis: a large
      cohort study.
AB  - To investigate the clinical pattern, survival rate, causes of death and risk
      factors in a large cohort of Chinese Han patients with systemic sclerosis (SSc).
      Inpatients treated from 2002 to 2014 were included in this study. Patients were
      classified into diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and
      SSc-overlap syndrome groups. Data were analyzed using Chi-squared tests, Kaplan
      Meier curves, log-rank tests, and Cox proportional hazards modeling. Among a
      total of 201 patients, dcSSc (50.2%) was the major subtype, followed by lcSSc
      (30.3%) and SSc-overlap (19.4%). Interstitial lung disease (ILD, 148/201, 74%)
      was the most frequent organ involvement. The overall survival rates were 98% and
      95% at 5 and 10 years, respectively. The overall standard mortality ratio (SMR)
      was 2.22. The most common cause of death was ILD combined with infection (8/16,
      50%), followed by kidney failure (2/16, 12.5%). On crude analysis, pulmonary
      hypertension, ILD, cardiac involvements, renal involvements, and digital ischemia
      were associated with poor prognosis. On multivariate analysis, pericardial
      effusion (p = 0.000) and digital ischemia (p = 0.016) were independent prognostic
      factors of death. The mortality rate of patients with SSc is mildly increased in
      comparison with the general population. ILD is the most common systemic
      involvement and the principal cause of death in SSc. Pericardial effusion and
      digital ischemia are independent factors associated with death.

PMID- 30225559
TI  - Serum interleukin-37 level and interleukin-37 gene polymorphism in patients with
      Behcet disease.
AB  - Behcet's disease (BD) is a chronic inflammatory disease. The etiopathogenesis of
      BD is not well understood and several cytokines and genetic factors have been
      investigated. Interleukin (IL)-37, which a member of IL-1 family is an anti
      inflammatory cytokine. The aim of the study was to analyze serum IL-37 level and
      IL-37 gene polymorphisms to assess its possible role in BD. Two hundred twenty
      three patients with BD and 80 healthy controls (HC) were enrolled. Serum IL-37
      level was measured using an enzyme-linked immunosorbent assay (ELISA). Deoksiribo
      Nucleic acids (DNA) were extracted using a genomic DNA isolation kit. Single
      nucleotide polymorphism (SNP) of IL-37 gene (rs3811047) was performed using
      polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP)
      methods. Serum IL-37 level was not significantly different in BD and HC (p >
      0.05). Serum IL-37 level was not associated with the disease activity (p > 0.05).
      However, its level was higher in mucocutaneous involvement compared with systemic
      involvement (p = 0.002) and HC (p = 0.005). IL-37 gene polymorphisms were similar
      in BD and HC (p > 0.05). IL-37 may play a role in the etiopathogenesis of BD by
      contributing to manifestation with more moderate clinical symptoms.

PMID- 30225560
TI  - Coronary Renal Shunt with Splenectomy (CRSS) for Selective Variceal
      Decompression.
AB  - BACKGROUND: Distal splenorenal shunt and coronary caval shunt are commonly used
      for selective decompression of esophagogastric varices, but they may not solve
      severe hypersplenism and their application may be hampered by the presence of
      splenic venous thrombosis or a left gastric vein (LGV) situated deeply behind the
      pancreas. On the other hand, some patients have an LGV entering the splenic vein
      (SV). We tried to work out a new selective shunt for this group of patients.
      METHODS: Sixteen patients with severe hypersplenism and esophagogastric varices
      received coronary renal shunt using the SV following splenectomy. After
      splenectomy, the proximal portion of the SV and the LGV was isolated from the
      pancreas. The isolated SV was divided at a point 3-5 cm left to its junction with
      the LGV. The proximal orifice was anastomosed to the left renal vein, and the
      distal orifice was ligated. A clip was applied to the SV for occlusion between
      the portal vein and LGV. The right gastric and gastroepiploic vessels were
      divided to block backflow from the portal vein and to reduce the arterial inflow
      of the varices. RESULTS: No operative mortality or procedure-related
      complications occurred. Postoperative computed tomography and endoscopy showed
      that all the shunts were patent and that the varices had been obliterated or
      markedly alleviated. In the 6-36 months' follow-up period, no recurrent variceal
      hemorrhage or encephalopathy occurred. CONCLUSION: Coronary renal shunt combined
      with splenectomy can achieve the goal of selective decompression of
      esophagogastric varices. It would become an alternative means of selective
      variceal decompression for patients whose LGV enters the SV.

PMID- 30225561
TI  - Risk Factors for Late-Onset Gastrointestinal Hemorrhage After
      Pancreatoduodenectomy for Pancreatic Cancer.
AB  - BACKGROUND: Late-onset gastrointestinal hemorrhage after pancreatoduodenectomy
      (PD) occasionally occurs repeatedly or leads to a serious condition. This
      retrospective study aimed to clarify its frequency and pathogenesis. METHODS: A
      total of 147 consecutive patients who underwent PD for pancreatic cancer between
      2006 and 2014 were evaluated. Patients were divided into two groups according to
      the occurrence of late-onset gastrointestinal hemorrhage on postoperative day 100
      or later. Furthermore, recurrence and portal vein (PV) hemodynamics were
      thoroughly reevaluated by computed tomography. RESULTS: Eleven patients
      experienced late-onset gastrointestinal hemorrhage. The bleeding sites were
      gastrojejunostomy in four patients, choledochojejunostomy in two, transverse
      colic marginal vein in one, and unknown in four. The median occurrence time of
      late-onset gastrointestinal hemorrhage was 13.3 months after PD. PV occlusion
      (63.6 vs. 8.9%; p < 0.001), no patency of PV-splenic vein (SPV) confluence (54.5
      vs. 12.7%; p = 0.002), and SPV ligation (36.4 vs. 9.6%; p = 0.025) were found to
      be significant risk factors for late-onset gastrointestinal hemorrhage. Among 11
      patients who experienced late-onset gastrointestinal hemorrhage, 7 had PV
      occlusion and 6 had local recurrence. CONCLUSIONS: Our data suggested for the
      first time that both oncologic and non-oncologic factors might contribute to late
      onset gastrointestinal hemorrhage after PD for pancreatic cancer. Furthermore, PV
      occlusion, no PV-SPV patency, and SPV ligation were found to be significant risk
      factors for late-onset gastrointestinal hemorrhage. Therefore, to prevent late
      onset gastrointestinal hemorrhage, we must consider various approaches to
      maintain the patency of the PV and SPV.

PMID- 30225562
TI  - Invited Commentary to Static Prognostic Factors and Appropriate Surgical Designs
      of Patients with MTC: The 2nd Report of a Single-Institution Study in Japan.

PMID- 30225564
TI  - Appropriateness of Subadventitial Resection for Invasion of the Carotid Artery by
      Papillary Thyroid Carcinoma.
AB  - BACKGROUND: Selection of surgical treatment for patients with papillary thyroid
      carcinoma (PTC) that includes great vessel invasion is challenging. We
      investigated the efficacy of tumor excision, with regard to safety of the
      surgical procedure and prognosis among patients with PTC invasion of the carotid
      or vertebral artery. METHODS: This study is a retrospective review of patients
      who underwent surgical excision for PTC at our institution, between 1981 and
      2010, with 49 patients treated for carotid artery invasion and nine for vertebral
      artery invasion. RESULTS: Twenty patients with carotid artery invasion receiving
      initial treatment underwent subadventitial resection. Among 29 relapsing patients
      with carotid artery invasion, subadventitial resection was performed in 27 and en
      block resection and reconstruction in the other two. In patients with carotid
      artery invasion, locoregional recurrence was identified in 14 patients, with the
      recurrence specific to the carotid artery in one case and distant recurrence in
      15. The 10-year disease-specific survival rate was shorter among relapsing
      patients (21.7%) than among those receiving an initial treatment (69.3%). At 8
      years after surgery, however, the survival rates were comparable between the two
      groups. Of the nine patients with vertebral artery invasion, two received initial
      treatment, with either preservation or reconstruction of the vertebral artery.
      The other six cases were tumor recurrences, treated by tumor and vertebral artery
      resection. Vertebral artery invasion was associated with carotid artery invasion
      in five patients and subclavian artery invasion in four. CONCLUSIONS: Carotid
      artery invasion by PTC did not extend beyond the adventitia of the artery in the
      majority of patients. Most patients with vertebral artery invasion required tumor
      excision with vertebral artery resection.

PMID- 30225563
TI  - The Impact of Prior Laparotomy and Intra-abdominal Adhesions on Bowel and
      Mesenteric Injury Following Blunt Abdominal Trauma.
AB  - BACKGROUND: Early recognition of bowel and mesenteric injury following blunt
      abdominal trauma remains difficult. We hypothesized that patients with intra
      abdominal adhesions from prior laparotomy would be subjected to visceral sheering
      deceleration forces and increased risk for bowel and mesenteric injury following
      blunt abdominal trauma. METHODS: We performed a multicenter retrospective cohort
      analysis of 267 consecutive adult trauma patients who underwent operative
      exploration following moderate-critical (abdominal injury score 2-5) blunt
      abdominal trauma, comparing patients with prior laparotomy (n = 31) to patients
      with no prior laparotomy (n = 236). Multivariable regression was performed to
      identify predictors of bowel or mesenteric injury. RESULTS: There were no
      significant differences between groups for injury severity scores or findings on
      abdominal ultrasound, diagnostic peritoneal aspirate/lavage, pelvic radiography,
      or preoperative CT scan. The prior laparotomy cohort had greater incidence of
      full thickness bowel injury (26 vs. 9%, p = 0.010) and mesenteric injury (61 vs.
      31%, p = 0.001). The proportion of bowel and mesenteric injuries occurring at the
      ligament of Treitz or ileocecal region was greater in the no prior laparotomy
      group (52 vs. 25%, p = 0.003). Prior laparotomy was an independent predictor of
      bowel or mesenteric injury (OR 5.1, 95% CI 1.6-16.8) along with prior abdominal
      inflammation and free fluid without solid organ injury (model AUC: 0.81, 95% CI
      0.74-0.88). CONCLUSIONS: Patients with a prior laparotomy are at increased risk
      for bowel and mesenteric injury following blunt abdominal trauma. The
      distribution of bowel and mesenteric injuries among patients with no prior
      laparotomy favors embryologic transition points tethering free intraperitoneal
      structures to the retroperitoneum.

PMID- 30225565
TI  - Arthroscopic excision of wrist ganglions: does trans-cystic or cystic-sparing
      portal technique affect clinical outcomes?
AB  - INTRODUCTION: The preliminary results of arthroscopic wrist ganglionectomy were
      contradictory. The approach used for the arthroscopic excision of wrist ganglions
      may play an important role. We analyzed two surgical approaches for arthroscopic
      excision of wrist ganglions. MATERIALS AND METHODS: Between April 2009 and
      October 2014, 49 patients with wrist ganglions who underwent arthroscopic
      excision in our institute were retrospectively classified into two treatment
      groups, namely the trans-cystic portal technique (TCP) and cyst-sparing portal
      technique (CSP). The visual analog scale (VAS), Mayo wrist scores, and
      disabilities of the arm, shoulder, and hand (DASH) scores were measured for
      clinical assessment. Recurrence, residual pain, and complications were evaluated
      at follow-up. RESULTS: No significant differences were found between the groups
      in terms of demographic data, and preoperative clinical assessment, as well as
      with regard to postoperative VAS score (p = 0.898), Mayo wrist score (p = 0.526),
      DASH score (p = 0.870), recurrence (p = 0.491), residual pain (p = 0.690), and
      complications (p = 0.352). Recurrence was found in 2 of the 47 patients and they
      were both in the CSP group. At the final follow-up, residual pain was found in
      four patients in the TCP group and three in the CSP group. CONCLUSIONS: For
      performing arthroscopic resection of wrist ganglions, both techniques are safe
      regarding the complication rates. In recurrence rate, no significant difference
      was found between the two groups, but no recurrence was observed when the TCP
      technique was used.

PMID- 30225566
TI  - Cochlear implant device activation after 7 days in cochlear implant recipients.
AB  - INTRODUCTION: Cochlear implantation (CI) has become widely accepted as a safe and
      effective treatment in the clinically routine for patients, who suffer from
      severe to profound sensorineural hearing loss. The general recommendation for
      speech processor activation was 4 weeks after cochlear implantation. The aim of
      the study was to investigate whether cochlear implantation activation is possible
      7-day postoperation. METHODS: A total of 54 patients undergoing CI surgery were
      recruited to participate in this study. Participants were divided into 2 groups:
      an early-fit group (n = 34) whose devices were activated 7 days after surgery and
      standard-fit group (n = 20) whose devices were activated after 4 weeks post
      surgery. Measures of impedance and maximum comfortable loudness (MCL) levels were
      used to compare differences across the two groups. Data were measured at the
      initial stimulation session and also at 4 weeks after the initial stimulation
      session. Impedance values of intraoperative tests were also measured. Aided
      hearing threshold was measured 4 weeks after initial activation for both groups.
      RESULTS: No adverse events were reported post-operatively. These differences in
      impedance were observed across the two groups in the first mapping session but
      not in the intraoperative tests and follow-up session for each channel. There
      were no statistically significant differences between MCL in initial stimulation
      session and follow-up session between the two groups. There was no significant
      difference in aided hearing threshold postoperatively between the two groups.
      CONCLUSION: The results in the current study demonstrated that the early
      activation at 7-day post cochlear implantation did not impact the healing process
      of the incision site or the evolution of the impedance and stimulation levels.
      That early activation of the CI is safe and feasible.

PMID- 30225567
TI  - Outcome of compartment resection of locally advanced oral cancers extending to
      infratemporal fossa: a tertiary rural hospital experience.
AB  - Locally advanced oral cancers extending to infratemporal fossa (ITF) are a
      challenge to head and neck surgeons. These tumors are classified as T4b whenever
      the masticator space (MS), pterygoid muscles (PM), and pterygoid plates (PP) are
      involved according to AJCC classification. Until recently, these tumors were
      considered inoperable and treated only with palliative intent. However, a few
      studies in the last decade showed that many of these tumors could be resected
      with a reasonably favorable prognosis by compartment resection of ITF,
      particularly when the tumor was below sigmoid notch of mandible. A few studies
      attempted to downstage these tumors by neo-adjuvant chemotherapy before
      attempting resection. Oral Squamous cell carcinoma has a high prevalence in South
      India. Majority of these patients are females addicted to tobacco quid chewing
      and present with locally advanced disease. In this retrospective analysis, we
      evaluated the outcome of treatment of oral squamous cell carcinoma extending to
      ITF and staged T4b in 52 patients. All patients underwent Composite resection
      including compartment resection of ITF followed by adjuvant treatment. 20
      patients had received neo-adjuvant chemotherapy. Pectoralis major myocutaneous
      flap was the mainstay of reconstruction. After mean follow-up of 2 years, 31
      patients are alive and disease free. 14 patients had local recurrence in ITF and
      2 patients had recurred in cervical nodes. 8 patients died due to disease and 6
      are on palliative care. Neo-adjuvant chemotherapy did not benefit the outcome.
      Close margins of resection, extra nodal spread from lymph nodes and supra notch
      and involvement of posterior part of ITF were factors which predisposed to
      recurrence.

PMID- 30225568
TI  - Aptamer based electrochemiluminescent determination of bisphenol A by using
      carboxylated graphitic carbon nitride.
AB  - An electrochemiluminescence (ECL) based assay is described for the determination
      of the endocrine disruptor bisphenol A (BPA). The method is based on the use of
      carboxylated graphitic carbon nitride (C-g-C3N4) carrying an immobilized aptamer
      against BPA. In the presence of BPA, the ECL signal decreases due to ECL energy
      transfer from excited-state C-g-C3N4 to the BPA oxidation product. Under the
      optimal conditions, ECL intensity increases linearly in the 0.1 pM to 1 nM BPA
      concentration range. The detection limit is as low as 30 fM. The assay has
      excellent sensitivity, outstanding stability and high selectivity. It was applied
      to the determination of BPA in spiked water samples. Graphical abstract Aptamer
      modified carboxylated graphitic carbon nitride was synthesized and applied in an
      electrochemiluminescence-based aptasensor for bisphenol A.

PMID- 30225569
TI  - Backbone and side chain NMR assignments for the ribosome binding factor A (RbfA)
      from Staphylococcus aureus.
AB  - Ribosome binding factor A (RbfA) is a 14.9 kDa adaptive protein of cold shock,
      which is important for bacterial growth at low temperatures. RbfA can bind to the
      free 30S ribosomal subunit and interacts with the 5'-terminal helix (helix I) of
      16S rRNA. RbfA is important for the efficient processing of 16S rRNA and for the
      maturation (assembly) of 30S ribosomal subunits. Here we report backbone and side
      chains 1H, 13C and 15N chemical shift assignments of RbfA from Staphylococcus
      aureus. Analysis of the backbone chemical shifts by TALOS+ suggests that RbfA
      contains four alpha-helixes and three beta-strands with alpha1-beta1-beta2-alpha2
      alpha3-beta3-alpha4 topology. Secondary structure of RbfA have KH-domain fold
      topology with betaalphaalphabeta subunit which is characterized by a helix-kink
      helix motif in which the GxxG sequence is replaced by a conserved AxG sequence,
      where an Ala residue at position 70 forming an interhelical kink. The solution of
      the structure of this protein factor and its complex with the ribosome by NMR
      spectroscopy, X-ray diffraction analysis and cryo-electron microscopy will allow
      further development of highly selective substances for slowing or completely
      stopping the translation of the pathogenic bacterium S. aureus, which will
      interfere with the synthesis and isolation of its pathogenicity factors.

PMID- 30225570
TI  - Dimensions of sedentary behavior and objective cognitive functioning in breast
      cancer survivors.
AB  - PURPOSE: To examine associations between dimensions of sedentary behavior and
      cognitive function in breast cancer survivors. METHODS: Sedentary behavior
      variables were measured using thigh-worn activPALs, and included total daily
      sitting time, time in long sitting bouts, sit-to-stand transitions, and standing
      time. Cognitive function was assessed using the NIH Toolbox Cognitive Domain.
      Separate multivariable linear regression models were used to examine associations
      between sedentary behavior variables with the cognitive domain scores of
      attention, executive functioning, episodic memory, working memory, and
      information processing speed. RESULTS: Thirty breast cancer survivors with a mean
      age of 62.2 (SD = 7.8) years who were 2.6 (SD = 1.1) years since diagnosis
      completed study assessments. In multivariable linear regression models, more time
      spent standing was associated with faster information processing (b: 5.78; p =
      0.03), and more time spent in long sitting bouts was associated with worse
      executive function (b: -2.82; p = 0.02), after adjustment for covariates. No
      other sedentary behavior variables were statistically significantly associated
      with the cognitive domains examined in this study. CONCLUSIONS: Two important
      sedentary constructs that are amenable to intervention, including time in
      prolonged sitting bouts and standing time, may be associated with cognitive
      function in breast cancer survivors. More research is needed to determine whether
      modifying these dimensions of sedentary behavior will improve cognitive function
      in women with a history of breast cancer, or prevent it from declining in breast
      cancer patients.

PMID- 30225571
TI  - The risk factors for depression in cancer patients undergoing chemotherapy: a
      systematic review.
AB  - PURPOSE: This systematic review aims to identify the risk factors for depression
      in cancer patients undergoing chemotherapy. METHODS: Eight electronic databases
      were searched from inception of the databases established until August 2017.
      References for the included studies were retrieved by manual searching. The
      quality of the eligible studies was appraised by two persons using the 11-item
      checklist of the Agency for Healthcare Research and Quality (AHRQ). RESULTS:
      Among 5988 potentially relevant articles, 43 studies were eligible, with 17
      studies of high quality and 25 studies of moderate quality. A total of 65 factors
      were extracted, including sociodemographic characteristics (n = 20),
      physiological condition (n = 20), disease and treatment (n = 12), and
      psychosocial factors (n = 13). Only social support, anxiety, perceived stress,
      and self-efficacy were found to be consistently associated with depression in
      cancer patients. There is not enough evidence to support the link between the
      other 61 factors and depression in cancer patients undergoing chemotherapy.
      CONCLUSIONS: This review suggests that the development of depression programs
      should take social support, anxiety, perceived stress, and self-efficacy into
      account. More original studies with rigorous design are necessary to further
      confirm those 61 inconclusive risk factors for depression in cancer patients
      receiving chemotherapy.

PMID- 30225572
TI  - Establishing an integrative oncology service in the Australian healthcare setting
      the Chris O'Brien Lifehouse Hospital experience.
AB  - Comprehensive cancer centres are on the rise as patients seek a more holistic
      approach to maintaining their wellbeing when living with a cancer diagnosis. Many
      cancer centres worldwide now incorporate a selection of evidence-based
      complementary therapies and qualified therapists into their offerings. The Chris
      O'Brien Lifehouse, a comprehensive cancer centre in Sydney, Australia, provides
      integrative oncology services including acupuncture, massage, reflexology,
      dietetics and exercise physiology for individual patients, along with group
      programmes, and an integrative and supportive care medical specialist. The
      purpose of this paper is to reflect on one model of integrative oncology service
      and approach to integration and team and service development.

PMID- 30225573
TI  - Social correlates of mental health in gastrointestinal cancer patients and their
      family caregivers: Exploring the role of loneliness.
AB  - PURPOSE: The present study examined the degree to which loneliness mediated the
      influence of negative (social constraints) and positive (emotional support)
      relationship qualities on the global mental health of advanced gastrointestinal
      (GI) cancer patients and their family caregivers. METHODS: Fifty patient
      caregiver dyads completed measures assessing social constraints (e.g., avoidance,
      criticism) from the other dyad members, emotional support from others,
      loneliness, and global mental health. Structural equation modeling was used to
      examine individual models, and Actor-Partner Interdependence Mediation Modeling
      was used to examine dyadic associations. RESULTS: Individual path analyses for
      patients and caregivers demonstrated that emotional support had a significant
      indirect effect on mental health through loneliness (Bs = 0.32 and 0.30,
      respectively), but no associations were found between social constraints and
      mental health. In dyadic analyses, participants' loneliness and mental health
      were not significantly related to their partner's emotional support, loneliness,
      or mental health (Bs = - 0.18 to 0.18). CONCLUSIONS: Findings suggest that for
      advanced GI cancer patients and caregivers, emotional support from others
      alleviates feelings of loneliness, which may lead to better mental health.
      However, the benefits of emotional support appear to be primarily intrapersonal
      rather than interpersonal in nature. Additionally, participants endorsed low
      levels of social constraints, which might explain their lack of relation to
      loneliness and mental health. Continued examination of interdependence in social
      processes between cancer patients and caregivers will inform intervention
      development.

PMID- 30225574
TI  - A low literacy targeted talking book about radiation therapy for cancer:
      development and acceptability.
AB  - PURPOSE: To develop a low literacy talking book (written book with accompanying
      audio-recording) about radiation therapy and explore its acceptability with
      patients and caregivers. METHOD: The talking book was developed iteratively using
      low literacy design principles and a multidisciplinary committee comprising
      consumers and experts in radiation oncology, nursing, behavioural sciences, and
      linguistics. It contained illustrations, photos, and information on: treatment
      planning, daily treatment, side effects, psychosocial health, and a glossary of
      medical terms. Semi-structured interviews were conducted with patients who self
      reported low functional health literacy and caregivers to explore their views on
      the resource. Thematic analysis using a framework approach informed the analysis.
      RESULTS: Participants were very satisfied with the content, illustrations, and
      language in the resource. Most were unfamiliar with the term 'talking book', but
      liked the option of different media (text and audio). The resource was seen as
      facilitating communication with the cancer care team by prompting question-asking
      and equipping patients and their families with knowledge to communicate
      confidently. CONCLUSIONS: The low literacy talking book was well accepted by
      patients and their caregivers. The next step is to examine the effect of the
      resource on patients' knowledge, anxiety, concerns, and communication with the
      cancer care team.

PMID- 30225575
TI  - A missed opportunity? Cannabis legalization and reparations in Canada.
AB  - As Canada moves towards the legalization of cannabis, the Cannabis Act itself
      remains void of any complementary social justice measures. Decades of
      criminalization for the possession, production, and sale of cannabis will remain
      unscathed under this ostensibly new approach, leaving intact laws that have
      disproportionately and prejudicially impacted Indigenous people and people of
      colour. This includes the overpolicing and criminalization of these communities,
      furthering criminal justice disparities, and the lack of meaningful initiatives
      to aid communities of colour and Indigenous communities in participating in the
      legal cannabis industry. Despite the continuing impacts, the Government of Canada
      has made no commitment to tandem initiatives that address the issues of
      reparation for those who have been most heavily targeted under cannabis
      prohibition. Public health implications are discussed.

PMID- 30225576
TI  - Workplace exposure to asbestos and the risk of kidney cancer in Canadian men.
AB  - OBJECTIVE: Previous studies considered the role of occupational causes in kidney
      cancer but were limited by small sample sizes and imprecise exposure assessment.
      This study examined the relationship between occupational exposure to asbestos
      and the risk of kidney cancer across a range of jobs in a large, population-based
      case-control study in Canada. METHODS: Data were from the case-control component
      of the National Enhanced Cancer Surveillance System, a study conducted between
      1994 and 1997 in eight Canadian provinces. Male kidney cancer cases,
      histologically confirmed, and controls completed questionnaires on socio
      demographics, anthropometry, diet, smoking, secondhand smoke exposure, and
      physical activity. Occupational histories were also collected, including each job
      held for at least 1 year since the age of 18. Occupational hygienists, blinded to
      case status, assigned exposure to asbestos, considering intensity, frequency, and
      probability of exposure (each 3-point scales). Logistic regression was used to
      estimate the odds of kidney cancer in exposed participants (defined using three
      metrics) compared to those without asbestos exposure. RESULTS: There were 712
      cases and 2454 controls in these analyses. Ever-exposure to asbestos was
      associated with 20% increased odds of kidney cancer compared to unexposed workers
      (OR 1.2, 95% confidence interval 1.0-1.4 when including possibly exposed
      workers). A small increase in risk was observed with cumulative exposure, while
      increasing intensity of exposure was related to increased odds of kidney cancer.
      CONCLUSIONS: This study found some evidence for an association between
      occupational exposure to asbestos and kidney cancer. Higher intensity of exposure
      to asbestos had the strongest relationship with kidney cancer risk.

PMID- 30225577
TI  - Endovascular treatment of ruptured intracranial aneurysms in elderly patients:
      clinical features and treatment outcome.
AB  - Management of ruptured intracranial aneurysm in elderly patients is still a major
      challenge in the treatment of cerebrovascular disease. This study aimed to
      evaluate safety and efficacy profiles of ruptured intracranial aneurysms in
      elderly patients treated with endovascular techniques (EVTs). We conducted a
      retrospective case review of 53 consecutive elderly patients with ruptured
      intracranial aneurysms treated by EVT between the year 2011 and 2016. The
      patients' angiographic outcomes, clinical outcomes, and procedure-related
      complications were reviewed retrospectively. Univariate and multivariate logistic
      analysis were applied to determine the risk factors of aneurysm recurrence and
      clinical prognosis. In 29 (54.7%) patients, the treatment was attempted with
      coiling alone. The vascular remodeled technique was applied in 24 (45.3%)
      patients. At a median angiographic follow-up of 9 months, 35 (67.3%) aneurysms
      showed stable, 9 (17.3%) were improvement, and 8 (15.4%) were recurrent.
      According to the multivariate analysis, the size of the aneurysm was
      independently associated with increased risk of aneurysm recurrence (odds ratio,
      1.92; 95% confidence interval, 1.181-2.211; p = 0.006). High Hunt-Hess grade at
      admission was an independent predictor of poor functional outcome in the
      multivariate analysis (odds ratio, 5.93; 95% confidence interval, 1.878-33.63; p
      = 0.008). In 8 (15.1%) patients, it resulted in procedure-related complications.
      EVT of ruptured intracranial aneurysms in elderly patients is safe, effective,
      and have low recurrent rate. Recurrence after EVT for ruptured aneurysms is
      common in cases of large-size aneurysms. The overall clinical outcome was worst
      in patients presented with high Hunt-Hess grade.

PMID- 30225578
TI  - Disability Determination Under Social Security: Increasing Rates of Approval.
AB  - Supplemental security income (SSI), is the lifeline for our patients living in
      the community. Absent disability benefits most of our patients are homeless. Many
      will be hungry, poorly clothed, and have only rudimentary health care. The
      disability determination system will approve disability for < 30% of those adults
      making an initial application. The rate of actual disability is much higher. A
      large cohort (n = 251) of likely disability applicants had comprehensive
      diagnostic evaluations. These evaluations revealed extensive co-occurring
      psychiatric symptoms and features, particularly obsessive-compulsive features.
      Recognition and appreciation of the burden of co-occurring conditions leads to a
      robust increase in approval rates. Administrative or structural features of the
      disability determination system also depress allowance rates.

PMID- 30225579
TI  - Artery of Percheron territory infarct due to bilateral carotid artery dissection:
      when anterior circulation supplies the posterior one.

PMID- 30225580
TI  - Core Semantic Links or Lexical Associations: Assessing the Nature of Responses in
      Word Association Tasks.
AB  - The processes tapped by the widely-used word association (WA) paradigm remain a
      matter of debate: while some authors consider them as driven by lexical co
      occurrences, others emphasize the role of meaning-based connections. To test
      these contrastive hypotheses, we analyzed responses in a WA task in terms of
      their normative defining features (those describing the object denoted by the cue
      word). Results indicate that 72.5% of the responses had medium-to-high
      coincidence with such defining semantic features. Moreover, 75.51% of responses
      had medium-to-high values of Relevance (a measure of the importance of the
      feature for construing a given concept). Furthermore, most responses (62.7%)
      referred to elements of the situation in which the concept usually appears,
      followed by sensory properties (e.g., color) of the denoted object (27.86%).
      These results suggest that the processes behind WA tasks involve a reactivation
      of the cue item's semantic properties, particularly those most relevant to its
      core meaning.

PMID- 30225581
TI  - Evaluation of serum level of substance P and tissue distribution of NK-1 receptor
      in endometrial cancer.
AB  - Substance P (SP), a neuropeptide belonging to the tachykinin family, exerts
      different biological activities mainly through neurokinin-1 receptor (NK1R). The
      role of SP/NK1R system in tumoral growth and spread is reported in several
      cancers. We aimed to evaluate the serum SP concentration and NK1R tissue
      distribution in endometrial cancer, and to study the relationship between these
      factors with tumor size, lymph node involvement, disease stage and cancer grade.
      Recruiting 22 patients with endometrial cancer and 21 patients with leiomyoma as
      the control group, serum SP concentration was measured using an ELISA method, and
      NK1R tissue distributions were immunohistochemically analyzed. Serum SP
      concentration in patients was significantly higher than the control group (p
      value = 0.005). The expression level of NK1R in tumoral tissue was more than
      normal tissue (p-value < 0.001). The NK1R expression had a significant
      relationship with lymph node involvement (p-value = 0.005) and disease stage (p
      value = 0.017). The NK1R expression was higher in more advanced and less
      differentiated tumors. SP/NK1R system seems to play a role in tumor growth and
      development in endometrial cancer. As well, the NK1R expression increased in
      endometrial cancer, and may be considered as a prognostic factor; but further
      studies are needed in this field.

PMID- 30225582
TI  - Copy number profiling of Oncotype DX genes reveals association with survival of
      breast cancer patients.
AB  - Copy number variations (CNVs) are key contributors in breast cancer initiation
      and progression. However, to date, no CNV-based gene signature is developed for
      breast cancer. 21-gene Oncotype DX, a clinically validated signature, was
      identified using only RNA expression data in breast cancer patients. In this
      study, we evaluated whether CNVs of Oncotype DX genes can be used to predict the
      prognosis of breast cancer patients. Transcriptomic data of 547 and genomic data
      of 816 of breast cancer patients were downloaded from The Cancer Genome Atlas
      database. To establish the prognostic relevance between the CNVs of Oncotype DX
      genes and clinicopathological features, statistical analysis including Pearson
      Correlation, Fisher-exact, Chi square, Kaplan-Meier survival and Cox regression
      analyses were performed. 86% genes showed positive CNV-expression correlation.
      CNVs in 52% and 47.6% genes showed association with ER+ and PR+ status,
      respectively. 71% of the genes (including ERBB2, CTSV, CD68, GRB7, MKI67, MMP1,
      PGR, RPLP0, TFRC, BAG1, BCL2, BIRC5, FLNB, GSTM1 and SCUBE2) showed association
      with poor overall survival. 14% of the genes (including CTSV, RPLP0 and BIRC5)
      genes showed association with disease free survival. Cox regression analysis
      revealed ESR1, metastasis and node stage as independent prognostic factors for
      overall survival of breast cancer patients. The results suggested that CNV-based
      assay of Oncotype DX genes can be used to predict the survival of breast cancer
      patients. In future, identifying new gene signatures for better breast cancer
      prognosis using CNV level information will be worth investigating.

PMID- 30225583
TI  - Development of a novel anti-HER2 scFv by ribosome display and in silico
      evaluation of its 3D structure and interaction with HER2, alone and after fusion
      to LAMP2B.
AB  - HER2 is a member of epidermal factor receptor (EGFR) family which is
      overexpressed in breast cancer, ovarian cancer and gastric cancer. Development of
      new binders for cancer cell surface receptors and expressing them at the surface
      of exosomes would be a great approach in targeted cancer therapy. We found a high
      affinity scFv against HER2 using ribosome display with the approach of applying
      it as a targeting moiety at the surface of exosomes by fusion to lysosomal
      associated membrane protein 2B (LAMP2B). We also provide some structural
      information about the ribosome display selected scFv (scFv HFS2) through modeling
      the 3D structure of scFv HFS2 using RosettaAntibody and docked it at the
      extracellular domain of HER2. We also evaluated the structure of scFv HFS2 and
      its binding to HER2 after fusion to LAMP2B. Our results showed no significant
      change in 3D structure of scFv HFS2 when fused to LAMP2B (RMSD 1.3) and
      interaction analysis represented that scFv HFS2 binds HER2 domain III before and
      after fusion to LAMP2B. Although binding domain of scFv HFS2 on HER2 was the same
      at both state, residues involved in their interactions showed significant
      differences as it was probably due to the spatial hindrance of scFv HFS2 when
      fused to LAMP2B through a short linker and it should be considered before
      proceeding to experiment.

PMID- 30225584
TI  - Expression and characterisation of a thermophilic endo-1,4-beta-glucanase from
      Sulfolobus shibatae of potential industrial application.
AB  - An endo-1,4-beta-D-glucanase gene was cloned from the thermophilic archaea
      Sulfolobus shibatae and expressed in E. coli. The recombinant enzyme was purified
      by heat denaturation and affinity chromatography prior to characterisation. The
      purified recombinant enzyme exhibited maximum activity at 95-100  degrees C and
      displayed a broad pH profile with over 91% of its maximum activity observed at pH
      3-5. Upon assessment of enzyme thermal stability, full activity was observed
      after 1 h incubation at 75, 80 and 85  degrees C while 98%, 90% and 84% of
      original activity was detected after 2 h at 75, 80 and 85  degrees C,
      respectively. Maximum activity was observed on barley beta-glucan and lichenan
      and the purified enzyme also hydrolysed CMC and xylan. Endoglucanase activity was
      confirmed by viscometric assay with a rapid decrease in substrate viscosity
      observed immediately upon incubation with barley beta-glucan or CMC. The crude
      enzyme released reducing sugars from acid-pretreated straw at 75-85  degrees C.
      The thermophilic nature and biochemical properties of the enzyme indicate its
      potential suitability in industrial applications undertaken at high temperature,
      such as the production of second-generation bioethanol from lignocellulosic
      feedstocks and in the brewing industry. This is the first known report of an
      endoglucanase from S. shibatae.

PMID- 30225586
TI  - Common Infections May Lead to Alzheimer's Disease.

PMID- 30225585
TI  - Mechanisms for establishment of the placental glucocorticoid barrier, a guard for
      life.
AB  - The fetus is shielded from the adverse effects of excessive maternal
      glucocorticoids by 11beta-HSD2, an enzyme which is expressed in the syncytial
      layer of the placental villi and is capable of converting biologically active
      cortisol into inactive cortisone. Impairment of this placental glucocorticoid
      barrier is associated with fetal intrauterine growth restriction (IUGR) and
      development of chronic diseases in later life. Ontogeny studies show that the
      expression of 11beta-HSD2 is initiated at a very early stage after conception and
      increases with gestational age but declines around term. The promoter for
      HSD11B2, the gene encoding 11beta-HSD2, has a highly GC-rich core. However, the
      pattern of methylation on HSD11B2 may have already been set up in the blastocyst
      when the trophoblast identity is committed. Instead, hCG-initiated signals appear
      to be responsible for the upsurge of 11beta-HSD2 expression during trophoblast
      syncytialization. By activating the cAMP/PKA pathway, hCG not only alters the
      modification of histones but also increases the expression of Sp1 which activates
      the transcription of HSD11B2. Adverse conditions such as stress, hypoxia and
      nutritional restriction can cause IUGR of the fetus. It appears that different
      causes of IUGR may attenuate HSD11B2 expression differentially in the placenta.
      While stress and nutritional restriction may reduce HSD11B2 expression by
      increasing its methylation, hypoxia may decrease HSD11B2 expression via
      alternative mechanisms rather than by methylation. Herein, we summarize the
      advances in the study of mechanisms underlying the establishment of the placental
      glucocorticoid barrier and the attenuation of this barrier by adverse conditions
      during pregnancy.

PMID- 30225587
TI  - One-Stage Combined Postbariatric Surgery: A Series of 248 Procedures in 55 Cases.
AB  - INTRODUCTION: Combined and/or multistage operations often are needed in
      postbariatric surgery. AIM: With this retrospective study of a series of 55
      cases, we aim to determine the effectiveness and safety of one-stage combined
      postbariatric surgery. MATERIALS AND METHODS: A total of 248 postbariatric
      procedures were performed in one session (except one-staged gynecomastia case) in
      55 patients. The procedures included face and neck lifting, upper and lower trunk
      lifting, gluteal fat injection, mammoplasty, gynecomastia correction,
      abdominoplasty, and thigh and arm lifting. Sagged tissues of the trunk and
      extremities were removed by avulsing after tumescent liposuction. Liposuction was
      performed also on the neighboring tissues. Multilayer repair from superficial
      fascia to the skin was carried out after meticulous hemostasis and suction drain
      insertion. RESULTS: At least two plastic surgeons and two assistants entered the
      operations; operation time never exceeded 4.5 h except in one, and blood
      transfusion was needed only in one case. All patients were discharged from the
      hospital after 1 or 2 nights. Postoperative problems included infection (3.64% of
      the patients), delayed wound healing after seroma formation (32.73%), abnormal
      scar formation (1.82%), and demanded scar revision and revisionary liposuction by
      10 patients (18.18%). CONCLUSION: Combined postbariatric operations are very
      effective and the likelihood of serious complications could be decreased
      significantly when performed under certain conditions. The tumescent
      dermolipectomy method is a very useful method for these cases. LEVEL OF EVIDENCE
      IV: This journal requires that authors assign a level of evidence to each
      article. For a full description of these Evidence-Based Medicine ratings, please
      refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 30225588
TI  - Medial patellofemoral ligament reconstruction fails to correct mild patella alta
      in cases of patellofemoral instability-a case-control study.
AB  - PURPOSE: Medial patellofemoral ligament reconstruction (MPFL-R) is the gold
      standard in patella soft tissue surgery for patellofemoral instability. Although
      claimed, recent reports indicate that MPFL-R may fail to distalize the patella in
      mild cases of patella alta. The present study is a retrospective case-control
      study to compare radiographic patella height between MPFL-R and historical
      Insall's proximal realignment (IPR) pre- and post-operatively with respect to
      distalization and assess redislocation rates at a mid-term follow-up. METHODS:
      Sixty-four patients were age/sex matched (1:1), yielding 32 patients for group 1
      MPFL-R (cases) and 32 patients for group 2 IPR (controls). Insall-Salvati,
      Blackburne-Peel and Caton-Deschamps indices were analyzed for differences pre-
      and post-operatively. An additional inter-rater reliability analysis was
      performed by means of intra-class correlation (ICC). Redislocation rates were
      considered as treatment failures in this study. RESULTS: ICC was excellent for
      all three patella indices. MPFL-R failed to show significant differences if
      compared to IPR with respect to distalization in mild stages of patella alta.
      Moreover, redislocation rates significantly favored MPFL-R (3.1%) over IPR
      (12.5%; p < 0.0001). CONCLUSIONS: MPFL-R has become a popular option to restore
      native patellofemoral biomechanics after ligament rupture. However, the
      procedure's potential to correct concomitant patella alta should not be
      overestimated and indications considered carefully.

PMID- 30225589
TI  - Comparison between posterior sacral plate stabilization versus minimally invasive
      transiliac-transsacral lag-screw fixation in fractures of sacrum: a single-centre
      experience.
AB  - PURPOSE: The sacrum is a mechanical nucleus working as the base for the spinal
      column, as well as the keystone of the pelvic ring. Thus, injuries of the sacrum
      can lead to biomechanical instability and nerve conduction abnormality. METHODS:
      The common classification is the Denis classification, but these fractures are
      often part of a lesion of the posterior pelvic ring and therefore the Tile
      classification is very useful. The goals of operative intervention are to reduce
      fracture fragments, protect neurological structures, and provide adequate
      stability for early mobilization. RESULTS: The stabilization of these injuries
      can be difficult even in a patient with adequate bone stock and concomitant
      medical comorbidities. The posterior-ring tension-band metallic plate and
      sacroiliac joint screw are two commonly used methods for posterior internal
      fixation of the pelvis. CONCLUSIONS: In this study, we evaluate the differences,
      in the treatment of sacral fractures, between the two techniques, revising the
      literature and our experience.

PMID- 30225591
TI  - Avoidance-endurance fast screening (AE-FS) : Content and predictive validity of a
      9-item screening instrument for patients with unspecific subacute low back pain.

PMID- 30225590
TI  - [Parental responses to children's pain : Analysis of the parental responses to
      their child's pain in the German general population].
AB  - BACKGROUND: Parental reactions to their child's pain can comprise cognitive
      affective and behavioral responses. Dysfunctional responses like parental
      catastrophizing may lead to an aggravation of the child's pain. OBJECTIVES: Aims
      of the online-based study were (1) to psychometrically evaluate existing
      questionnaires into cognitive-affective (Pain Catastrophizing Scale for Parents;
      PCS-P) and behavioral responses (Inventar zum schmerzbezogenen Elternverhalten;
      ISEV-E) within a sample of 105 healthy parents, and (2) to compare their
      responses to existing (inter)national clinical samples and to the reactions of 80
      parents with self-reported chronic pain from the general population. METHODS: The
      assessment of parental pain-related reactions was online-based. RESULTS: While
      the factor structure of the ISEV-E could not be replicated, the three factors of
      the PCS-P could be replicated. Parental catastrophizing of the healthy parents
      was lower compared to clinical samples. Healthy parents did not differ from
      parents with chronic pain from the general population. CONCLUSION: The results
      offer a basis to grade parental catastrophizing, so that risk-groups can be
      identified.

PMID- 30225592
TI  - Reentry as an Origin for Rotors.
AB  - The aim of the study is to understand in depth the meaning of "reentry", and to
      decipher if and how it can lead to malfunctions of the heart and possibly of the
      brain. A simple model is used to reveal the mechanism by which a single pulse of
      action potential rotating around a ring of excitable medium, the latter
      simulating a reentry circuit, can generate spirals (single and/or double) when
      the pulse can emerge from and develop outside the ring. Two mechanisms of spiral
      generation are demonstrated: (1) a mechanism in which a source of single spirals
      is created at the contact with the core soon after the pulse freeing action,
      their chirality being due to the sense of the preceding pulse rotation.
      Interestingly, these spirals, adhering to the core, become "double-spiral
      patterns" while leaving behind the seeds of the new single spirals. (2) A second
      possible mechanism, similar to the known "arms encountering methods", in which a
      double spiral (a figure of eight) is repeatedly created on the other side of the
      core. Similar procedures are assumed to occur in the heart, leading to
      tachycardia and fibrillation and possibly in the brain leading to epilepsy. The
      exact processes of the hitherto assumed spiral generations by reentry were
      established. The novel deep understanding of the mechanisms involved in these
      processes can lead to new methods of treating heart fibrillation (e.g., by
      judicial ablation).

PMID- 30225593
TI  - Data-Driven Method for Efficient Characterization of Rare Event Probabilities in
      Biochemical Systems.
AB  - As mathematical models and computational tools become more sophisticated and
      powerful to accurately depict system dynamics, numerical methods that were
      previously considered computationally impractical started being utilized for
      large-scale simulations. Methods that characterize a rare event in biochemical
      systems are part of such phenomenon, as many of them are computationally
      expensive and require high-performance computing. In this paper, we introduce an
      enhanced version of the doubly weighted stochastic simulation algorithm (dwSSA)
      (Daigle et al. in J Chem Phys 134:044110, 2011), called dwSSA[Formula: see text],
      that significantly improves the speed of convergence to the rare event of
      interest when the conventional multilevel cross-entropy method in dwSSA is either
      unable to converge or converges very slowly. This achievement is enabled by a
      novel polynomial leaping method that uses past data to detect slow convergence
      and attempts to push the system toward the rare event. We demonstrate the
      performance of dwSSA[Formula: see text] on two systems-a susceptible-infectious
      recovered-susceptible disease dynamics model and a yeast polarization model-and
      compare its computational efficiency to that of dwSSA.

PMID- 30225594
TI  - Dimensions of Group-Based Phylogenetic Mixtures.
AB  - Mixtures of group-based Markov models of evolution correspond to joins of toric
      varieties. In this paper, we establish a large number of cases for which these
      phylogenetic join varieties realize their expected dimension, meaning that they
      are nondefective. Nondefectiveness is not only interesting from a geometric point
      of-view, but has been used to establish combinatorial identifiability for several
      classes of phylogenetic mixture models. Our focus is on group-based models where
      the equivalence classes of identified parameters are orbits of a subgroup of the
      automorphism group of the abelian group defining the model. In particular, we
      show that for these group-based models, the variety corresponding to the mixture
      of r trees with n leaves is nondefective when [Formula: see text]. We also give
      improved bounds for claw trees and give computational evidence that 2-tree and 3
      tree mixtures are nondefective for small n.

PMID- 30225595
TI  - [Tobacco control in Germany and worldwide].
AB  - In Germany, several tobacco control policies have been implemented since 2002.
      These include tobacco tax increases, restrictions on sale and advertising, smoke
      free legislation, and health warnings on tobacco products. All of those
      contributed to the emerging trend towards nonsmoking - especially among youth and
      young adults - as well as to the impressive decline of cigarette sales from 145.1
      billion cigarettes in 2002 to 75.8 billion in 2017. Despite this, still 13% of
      all deaths are attributable to smoking in Germany.Other countries are acting in a
      more committed manner and are implementing much stronger tobacco control policies
      than Germany. Germany is the only EU country that doesn't yet have a billboard
      ban on tobacco advertising, the smoke-free legislation is weak due to exceptions,
      and for more than ten years the tobacco tax has not been markedly increased.
      Globally, more than 30 countries have implemented at the highest possible level
      four of the six most important tobacco control policies as defined by the World
      Health Organization - Germany has implemented only two policies. Therefore, on an
      international scale, Germany is clearly lagging behind in tobacco control and on
      the European Tobacco Control Scale it is ranked second last. A more committed and
      compelling approach towards tobacco control is required in Germany to reach a
      position in terms of protecting the population from the devastating health
      hazards of smoking, which would be appropriate for a leading industrial nation.

PMID- 30225596
TI  - [Hepatitis C virus seroprevalence and dependency on country of origin of refugees
      in Rhineland-Palatinate, Germany in 2015].
AB  - BACKGROUND: Hepatitis C, a liver disease transmitted by the hepatitis C virus
      (HCV), can result in liver cirrhosis and hepatocellular carcinoma (HCC).
      According to WHO estimates for 2015, approximately 71 million people worldwide
      are chronically infected with HCV, representing 1% of the world population.
      Worldwide migration movements lead to immigration from HCV high- to low
      prevalence countries. There are, however, no published data available on HCV
      seroprevalence and its correlation with the country of origin in current
      unselected larger refugee populations (>1000 people) having entered
      Europe/Germany. OBJECTIVES: Documentation and evaluation of hepatitis C
      seroprevalence and its correlation with the country of origin of refugees in
      Rhineland-Palatinate/Germany in 2015. METHODS: As part of routine diagnostics
      during the initial medical examination, 12,880 refugees in Rhineland-Palatinate
      were screened for HCV antibodies in 2015. The data have been analyzed
      retrospectively and anonymously. RESULTS: The collective comprising 12,880
      refugees showed a HCV seroprevalence of 1.5%. This is higher than the HCV
      prevalence of the general German population (0.5%). In particular, a correlation
      between HCV seroprevalence and the country of origin could be demonstrated.
      CONCLUSIONS: To reach the 2030 HCV-elimination target of the WHO, national and
      international recommendations to screen refugees/migrants from HCV high
      prevalence countries for HCV should be emphasized. The chronically infected
      should be treated in accordance with HCV-guidelines. National, easily accessible
      information on HCV high-prevalence countries is required by attending physicians.

PMID- 30225597
TI  - Current Aura Without Headache.
AB  - PURPOSE OF REVIEW: This review evaluates and explains our current understanding
      of a rare subtype of migraine, typical aura without headache, also known as
      migraine aura without headache or acephalgic migraine. RECENT FINDINGS: Typical
      aura without headache is a known entity within the spectrum of migraine. Its
      pathophysiology is suggested to be similar to classic migraines, with cortical
      spreading depression leading to aura formation but without an associated
      headache. No clinical trials have been performed to evaluate treatment options,
      but case reports suggest that most patients will respond to the traditional
      treatments for migraine with aura. Bilateral greater occipital nerve blocks may
      be helpful in aborting migraine with prolonged aura. Transcranial magnetic
      stimulation has shown efficacy in aborting attacks of migraine with aura but has
      not been specifically tested in isolated aura. Typical aura without headache
      occurs exclusively in 4% patients with migraine, and may take place at some point
      in 38% of patients with migraine with aura. Typical aura without headache
      commonly presents with visual aura without headache, brainstem aura without
      headache, and can also develop later in life, known as late-onset migraine
      accompaniment.

PMID- 30225598
TI  - Unitization mitigates interference by intrinsic negative emotion in familiarity
      and recollection of associative memory: Electrophysiological evidence.
AB  - Emotion exerts varied influences on memory. While task-relevant item memory is
      often enhanced by emotion, associative memory is generally impaired. Unitization
      is known to improve associative memory, but its effects and mechanisms in
      protecting associative memory from emotional interference are rather obscure. The
      current study investigated associative memory by employing experimental
      manipulation of unitization (vs. nonunitization) encoding strategy and stimulus
      emotion (neutral, intrinsic negative, and extrinsic negative), combined with
      event-related potential (ERP) signatures of familiarity (FN400 old/new effects)
      and recollection (parietal late positive component/LPC old/new effects) in memory
      recognition. Both behavioral and ERP indices of associative recognition from the
      nonunitization group confirmed emotional interference in associative memory.
      Importantly, it was primarily intrinsic (vs. extrinsic) emotion that impeded
      associative memory. Unitization encoding improved memory performance in general,
      accompanied by enhanced recollection process and induction of familiarity
      process, which is typically not involved in associative memory recognition and
      was indeed absent in the nonunitization group. Importantly, unitization helped to
      preserve behavioral performance (specifically, response speed though not
      recognition strength) from interference by intrinsic emotion while largely
      reversed the detriment of intrinsic emotion on ERP indices of familiarity and
      recollection processes. Interestingly, a synergy between intrinsic emotion and
      unitization encoding was observed, which could underpin the facilitation of
      familiarity process in associative recognition of emotional pairs. Overall,
      current findings highlight interference by intrinsic emotion in associative
      memory, which is nonetheless responsive to mitigation by unitization encoding.

PMID- 30225599
TI  - Neural and behavioral effects of regulating emotional responses to errors during
      an implicit racial bias task.
AB  - Affect regulation plays a key role in several theories of racial bias reduction.
      Here, we tested whether engaging in emotion regulation strategies while
      performing an implicit racial bias task (Weapons Identification Task; WIT) would
      alter neural and behavioral manifestations of bias. Participants either
      suppressed or reappraised in a positive light the distress associated with making
      errors during the WIT, while an electroencephalogram (EEG) was recorded. We
      hypothesized that engaging in emotion regulation strategies would reduce the
      distress associated with making errors indicative of bias, resulting in smaller
      error-related negativity (ERN) amplitude during errors and increased expression
      of racial bias. Results of within-subjects comparisons (Experiment 1) generally
      supported these predictions. However, when emotion regulation strategies were
      manipulated between subjects (Experiment 2) there was no effect of suppression or
      reappraisal on bias expression. Across both experiments, engaging in emotion
      regulation led to larger ERNs for errors occurring on Black- relative to White
      primed trials. In addition, a number of significant order effects were observed,
      indicating important differences in the effects of engaging in emotion regulation
      strategies when those strategies are attempted in participants' first versus
      second block of trials. No such order effects were evident when a second trial
      block was completed with no emotion regulation instructions. Findings are
      discussed in terms of the need for greater specificity in experimental tests of
      emotion regulation on error processing and cognitive performance.

PMID- 30225600
TI  - Combining non-contrast and dual-energy CT improves diagnosis of early gout.
AB  - OBJECTIVES: To determine the incremental value of non-contrast CT (NCCT) on dual
      energy CT (DECT) in symptomatic first metatarsophalangeal (MTP) joints in early
      gout. METHODS: One hundred and fifteen painful joints were consecutively enrolled
      and gout was diagnosed based on the 2015 EULAR/ACR criteria and/or
      arthrocentesis. Two readers independently evaluated DECT alone and combined NCCT
      and DECT (NCCT+DECT) based on four semiquantitative scales. Sensitivities and
      specificities were compared using McNemar's test. AUC was compared. RESULTS: Of
      the 115 joints, 72 were defined as an early gout group and 43 as a gout-negative
      group after exclusion. The sensitivity and specificity for the early gout group
      on DECT alone were as followed: reader 1 - 52.8% and 100.0% and reader 2 - 51.4%
      and 100.0%. NCCT+DECT results were as follows: reader 1 - 79.2% and 93.0% and
      reader 2 - 79.2% and 95.3%. AUC was significantly higher in NCCT+DECT compared to
      that in DECT alone for the early gout group (0.888 vs. 0.774 for reader 1, p =
      0.0004; 0.896 vs. 0.816 for reader 2, p = 0.0142). The false-negative cases on
      DECT occurred more frequently with the first-onset gout, and tended to be
      affected by a longer duration of symptoms in the post-hoc analysis. CONCLUSION:
      The combined analysis of NCCT and DECT improves diagnostic capabilities in
      symptomatic early gout involving the first MTP joint. KEY POINTS: * MSU crystal
      depositions in early gout may be seen on non-contrast CT, while still being
      undetectable by DECT. * Combining non-contrast CT and DECT improves detection of
      early gout. * False negatives of DECT are more common than previously reported in
      cases of first-onset gout.

PMID- 30225602
TI  - Autophagy therapeutics: preclinical basis and initial clinical studies.
AB  - Autophagy captures and degrades intracellular components such as proteins and
      organelles to sustain metabolism and homeostasis. Rapidly accumulating attention
      is being paid to the role of autophagy in the development of cancer, which makes
      autophagy attractive tools and targets for novel therapeutic approaches.
      Functional studies have confirmed that autophagy dysregulation is causal in many
      cases of cancer, with autophagy acting as tumor suppressors or tumor promoters,
      and autophagy inhibitor or promoter has shown promise in preclinical studies. The
      autophagy-targeted therapeutics using chloroquine/hydroxychloroquine have reached
      clinical development for treating cancer, but these drugs are actually not
      efficient probably because of a reduced penetration within the tumor. In this
      review, we first discuss the discoveries related to dual function of autophagy in
      cancer. Then, we provide an overview of preclinical studies and clinical trials
      involved in the development of autophagy therapeutics and finally discuss the
      future of such therapies.

PMID- 30225601
TI  - Outcomes after neoadjuvant treatment with gemcitabine and erlotinib followed by
      gemcitabine-erlotinib and radiotherapy for resectable pancreatic cancer (GEMCAD
      10-03 trial).
AB  - BACKGROUND: Neoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC)
      patients has shown promising results in non-randomized trials. This is a multi
      institutional phase II trial of NAT in resectable PDAC patients. METHODS:
      Patients with confirmed resectable PDAC after agreement by two expert
      radiologists were eligible. Patients received three cycles of GEM (1000
      mg/m2/week) plus daily erlotinib (ERL) (100 mg/day). After re-staging, patients
      without progressive disease underwent 5 weeks of therapy with GEM (300
      mg/m2/week), ERL 100 mg/day and concomitant radiotherapy (45 Gy). Efficacy was
      assessed using tumor regression grade (TRG) and resection margin status. Using a
      single-arm Simon's design, considering the therapy not useful if R0 < 40% and
      useful if the R0 > 70% (alpha 5%, beta 10%), 24 patients needed to be recruited.
      This trial was registered at ClinicalTrials.gov, number NCT01389440. RESULTS:
      Twenty-five patients were enrolled. Adverse effects of NAT were mainly mild
      gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1%
      among the resected patients. Median overall survival (OS) and disease-free
      survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1),
      respectively. R0 resection patients had better median OS, compared with patients
      with R1 resection or not resected (65.5 months vs. 15.5 months, p = 0.01). N0
      rate among the resected patients was 63.1%, and showed a longer median OS (65.5
      vs. 15.2 months, p = 0.009). CONCLUSION: The results of this study confirm
      promising oncologic results with NAT for patients with resectable PDAC.
      Therefore, the present trial supports the development of phase II randomized
      trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.

PMID- 30225603
TI  - Ileal interposition coupled with duodenal diverted sleeve gastrectomy versus
      standard medical treatment in type 2 diabetes mellitus obese patients: long-term
      results of a case-control study.
AB  - BACKGROUND: Randomized controlled trials have demonstrated that bariatric surgery
      is effective in obtaining remission of type 2 diabetes mellitus (T2DM) in obese
      patients, yet no data exist in the literature from prospective studies with ileal
      interposition with duodenal diversion sleeve gastrectomy (II-DD-SG). The aim of
      this case-control study is to investigate if II-DD-SG is superior to medical
      treatment in T2DM obese patients. METHODS: Thirty obese patients (BMI > 30)
      affected by T2DM were recruited for surgery (II-DD-SG) between 2008 and 2011 and
      were matched with an equal control group which received standard medical
      treatment. Anthropometric measures, glucose metabolism, cardiovascular risk
      factors were determined baseline and during follow-up. The primary end point was
      T2DM remission; reduction of body weight, BMI, and cardiovascular risk factors
      were secondary end-points. RESULTS: Shortly after II-DD-SG, normalization of
      glucose plasma levels and glycated hemoglobin was observed followed by a
      significant decrease in body weight and BMI. At one-year follow-up, insulin
      resistance strongly declined as did insulin plasma levels. Complete remission was
      observed in 26 patients (86%); 2 (6.6%) had partial remission, and two (6.6%)
      were still diabetic. After 5 years, 17 of 25 patients on follow-up (68%) showed
      complete remission of T2DM and 56% had remission of cardiovascular risk factors.
      Only two patients receiving medical treatment showed complete remission of T2DM
      (p < 0.0001 versus II-DD-SG). No significant changes of anthropometric parameters
      and lipid metabolism were recorded. CONCLUSIONS: II-DD-SG is an effective
      surgical procedure, able to induce complete and prolonged remission of T2DM in
      obese patients as opposed to medical treatment.

PMID- 30225604
TI  - Robot-assisted versus laparoscopic Roux-en-Y gastric bypass and sleeve
      gastrectomy: a propensity score-matched comparative analysis using the 2015-2016
      MBSAQIP database.
AB  - BACKGROUND: Robotic-assisted bariatric surgery is part of the armamentarium in
      many bariatric centers. However, limited data correlate the robotic benefits to
      with clinical outcomes. This study compares 30-day outcomes between robotic
      assisted and laparoscopic procedures for Roux-en-Y gastric bypass (RYGB) and
      sleeve gastrectomy (SG). METHODS: Using the 2015-2016 Metabolic and Bariatric
      Surgery Accreditation and Quality Improvement Program (MBSAQIP) database,
      patients between18- and 65-year-old were included. To adjust for potential
      confounders, 1:1 propensity-score matching (PSM) was performed using 22
      preoperative characteristics. Second PSM analysis was performed adding operative
      time and conversion rate. RESULTS: 269,923 patients underwent SG (n = 190,494) or
      RYGB (n = 79,429). The operative time was significantly longer in the Robotic
      assisted compared to laparoscopic approach either for SG (102.58 +/- 46 vs. 73.38
      +/- 36; P < 0.001) or for RYGB (158.29 +/- 65 vs. 120.17 +/- 56; P < 0.001). In
      the SG cohort (12,877 matched cases), the robotic approach showed significant
      reduction of postoperative bleeding (0.16% vs. 0.43%; P < 0.001) and strictures
      (0.19% vs. 0.33%; P = 0.04) with similar results in the other 30-day outcomes in
      both analyses. Similarly, for the RYGB cohort (5780 matched cases), the robotic
      approach showed significantly fewer requirements for blood transfusions (0.64%
      vs. 1.16%; P = 0.004) with no statistically different results for the other's
      outcomes. Conversely, when adding operative time and conversion rate to the PSM
      analysis, the robotic platform showed significantly shorter length of stay (2.12
      +/- 1.9 vs. 2.30 +/- 3.1 days; P < 0.001), reduction of anastomotic leak (0.52%
      vs. 0.92%; P = 0.01), renal complications (0.16% vs. 0.38%; P = 0.004), and
      venous thromboembolism (0.24% vs. 0.52%; P = 0.02). CONCLUSIONS: Our findings
      show that postoperative bleeding and blood transfusion are significantly reduced
      with the robotic platform, and after correcting for all factors including
      operative time, the robotic-assisted approach is associated with better
      postoperative outcomes especially for RYGB.

PMID- 30225605
TI  - High cardiovascular risk patients benefit more from bariatric surgery than low
      cardiovascular risk patients.
AB  - INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) and Framingham risk
      scores (FRS) are used to calculate 10-year risk of coronary death, nonfatal
      myocardial infarction, or fatal/nonfatal stroke. Our goal is to evaluate the
      association between preoperative cardiovascular risk and weight loss. METHODS: We
      retrospectively reviewed bariatric surgeries from 2010 to 2016. Patients who met
      criteria for calculating 10-year ASCVD score and FRS were included. Data
      collected included baseline demographics, perioperative parameters, and
      postoperative outcomes at 12 months. Simple linear regression and multiple linear
      regression models were applied to test influence of individual or multiple
      factors of interest on 12-month weight loss outcomes. RESULTS: Of 1330 bariatric
      patients studied, 360 patients met criteria for ASCVD and FRS calculation. Sleeve
      gastrectomy (LSG) was the most prevalent surgery 63.05%, followed by Roux-en-Y
      gastric bypass (LRYGB) 20.55%, revision procedures 11.9%, and adjustable gastric
      banding (LAGB) 4.4%. Initial BMI was 42.71 +/- 7.85 kg/m2 for females and 42.72k
      +/- 7.42 kg/m2 for males, with a 12-month percentage of estimated BMI loss
      (%EBMIL) of 66.51% in females and 60.29% in males. Preoperative 10-year ASCVD
      score was higher in males than females with a 34.73% relative risk reduction
      (RRR) in males and 35.3% RRR in females at 12-month follow-up. Regarding FRS,
      preoperative risk was 33.13 +/- 21.1% in males and 15.71 +/- 14.52% in females,
      with an RRR of 25.8% in males and 32.2% in females. Univariate analysis of
      preoperative FRS and %EBMIL showed that for every percentage unit increase in the
      patient's preoperative FRS, %EBMIL decreases 0.31 percentile unit (P < 0.001).
      Furthermore, preoperative ASCVD score is also significantly associated with
      %EMBIL-for every percentage unit increase in preoperative ASCVD score, %EBMIL
      decreases 0.42 percentile credits. CONCLUSION: Study results suggest ASCVD and
      FRS are equally reduced after bariatric surgery, especially after LSG and LRYGB.
      Moreover, preoperative FRS and ASCVD risk score showed an inversely proportional
      relationship with %EBMIL loss at 12 months.

PMID- 30225606
TI  - Evaluating competency in video-assisted thoracoscopic surgery (VATS) lobectomy
      performance using a novel assessment tool and virtual reality simulation.
AB  - BACKGROUND: Competency-based training has gained ground in surgical training and
      with it assessment tools to ensure that training objectives are met. Very few
      assessment tools are available for evaluating performance in thoracoscopic
      procedures. Video recordings would provide the possibility of blinded assessment
      and limited rater bias. This study aimed to provide validity evidence for a newly
      developed and dedicated tool for assessing competency in Video-Assisted
      Thoracoscopic Surgery (VATS) lobectomy. METHODS: Participants with varying
      experience with VATS lobectomy were included from different countries. Video
      recordings from participants' performance of a VATS right upper lobe lobectomy on
      a virtual reality simulator were rated by three raters using a modified version
      of a newly developed VATS lobectomy assessment tool (the VATSAT) and analyzed in
      relation to the unitary framework (content, response process, internal structure,
      relation to other variables, and consequences of testing). RESULTS: Fifty-three
      participants performed two consecutive simulated VATS lobectomies on the virtual
      reality simulator, leaving a total of 106 videos. Content established in
      previously published studies. Response process Standardized data collection was
      ensured by using an instructional element, uniform data collection, a special
      rating program, and automatic generation of the results to a database. Raters
      were carefully instructed in using the VATSAT, and tryout ratings were carried
      out. Internal structure Inter-rater reliability was calculated as intra-class
      correlation coefficients, to 0.91 for average measures (p < 0.001). Test/re-test
      reliability was calculated as Pearson's r of 0.70 (p < 0.001). G-coefficient was
      calculated to be 0.79 with two procedures and three raters. By performing D
      theory was found that either three procedures rated by two raters or five
      procedures rated by one rater were enough to reach an acceptable G-coefficient of
      >= 0.8. Relation to other variables Significant differences between groups were
      found (p < 0.001). The participants' VATS lobectomy experience correlated
      significantly to their VATSAT score (p = 0.016). Consequences of testing The
      pass/fail score was found to be 14.9 points by the contrasting groups' method,
      leaving five false positive (29%) and six false negatives (43%). CONCLUSION:
      Validity evidence was provided for the VATSAT according to the unitary framework.
      The VATSAT provides supervisors and assessors with a procedure-specific
      assessment tool for evaluating VATS lobectomy performance and aids with the
      decision of when the trainee is ready for unsupervised performance.

PMID- 30225608
TI  - Platelet-rich plasma vs. steroid injections for hamstring injury-is there really
      a choice?
AB  - OBJECTIVE: To assess the effectiveness of pain relief in patients with grade 2
      proximal hamstring injury, treated with platelet-rich plasma (PRP) or
      corticosteroid injection, by using the primary outcome of visual analog scale
      (VAS) at 1 week and 4 weeks of follow-up. MATERIALS AND METHODS: A single
      institution retrospective study was performed for image-guided PRP or steroid
      injections between 12/1/2015 and 10/30/2017 for proximal hamstring injuries. VAS
      was measured at 1 week and 4 weeks post-injection via telephone interviews and
      the pain response was recorded into two groups (negative/no change vs. positive).
      A comparison of pain responses between PRP and steroid was conducted by
      generalized estimating equation. RESULTS: Among 56 patients, 32 received PRP and
      24 received steroid injections with ages from 13 to 75 years old. At 1 week post
      injection follow-up, 23 patients (71.9%) from the PRP group and 11 patients
      (45.8%) from the steroid group showed positive response. After controlling for
      age, pre-procedure pain level, and gender, the positive response rate in the PRP
      group was higher than the steroid group (aOR: 4.04, 95% CI: 1.04-15.63, p value =
      0.04). At 4 weeks post-injection, 23 patients (71.9%) from the PRP group and 13
      patients (54.2%) from the steroid group showed positive response with no
      statistical significance (aOR: 2.48, 95% CI: 0.63-9.79, p value = 0.19).
      CONCLUSIONS: The PRP group had shown more favorable response compared to steroid
      group at 1 week post-injection, which suggests that PRP therapy can be considered
      as a conservative treatment choice for grade 2 proximal hamstring injuries with
      better short-term pain relief based on limited pilot data.

PMID- 30225607
TI  - A pilot study assessing T1-weighted muscle MRI in amyotrophic lateral sclerosis
      (ALS).
AB  - The authors set out to study the role of T1-weighted muscle MRI in the diagnostic
      phase of ALS, comparing images from ten patients and nine age-matched healthy
      controls (HCs). All subjects underwent MRI of 68 muscles in the hands, paraspinal
      regions and lower limbs; the images were semi-quantitatively scored. Atrophy was
      more frequent in muscles of ALS patients than HCs (p < 0.0001); fatty
      infiltration was particularly marked in iliopsoas (p = 0.046), anterior (p =
      0.020) and posterior (p = 0.047) calf muscles in patients. A trend towards
      agreement was found between MRI and clinic-EMG data for the first dorsal
      interosseous, paraspinal, and tibial anterior muscles. Muscle T1-weighted MRI can
      distinguish ALS patients from HCs for specific regions (i.e., legs). MRI
      abnormalities could be found in pauci-symptomatic spinal muscles in bulbar-onset
      patients. Muscle MRI may be a useful diagnostic tool in ALS, in particular for
      muscles difficult to investigate using clinical-EMG methods.

PMID- 30225609
TI  - The role of contrast-enhanced computed tomography to detect renal stones.
AB  - PURPOSE: To investigate the detectability of renal stones in corticomedullary and
      nephrographic phases on contrast-enhanced computed tomography (CT). METHODS: All
      consecutive patients between January 2012 and February 2016 undergoing CT of the
      kidneys according to our department's standard four-phase protocol and having at
      least one stone in the NC-phase (NCP) were included. Fifty patients with
      altogether 136 stones were eligible. Two radiologists in consensus evaluated the
      NCP from each examination and documented the number, location, and size of
      stones. Three abdominal radiologists blinded to the findings of the NCP reviewed
      independently the corticomedullary and nephrographic phases on two different
      occasions. They reported the number and location of stones in each kidney. For
      the inter-observer agreement the intra-class correlation coefficient (ICC) was
      estimated. The detection rate of renal stones was calculated for the three
      radiologists and compared between the two contrast-enhanced phases and the
      results were analyzed with concern to the size of the stones. RESULTS: The ICC
      was 0.86. There was no statistically significant difference between
      corticomedullary and nephrographic phases (p = 0.94). The detection rate for
      stones measuring 3-5 mm was 82-88% and 98% for stones >= 6 mm. CONCLUSION: The
      detectability of renal stones >= 6 mm on contrast-enhanced CT is extremely high.
      This means that stones with a higher risk of not passing spontaneously can be
      safely diagnosed.

PMID- 30225610
TI  - Efficacy of perfusion CT in differentiating of pancreatic ductal adenocarcinoma
      from mass-forming chronic pancreatitis and characterization of isoattenuating
      pancreatic lesions.
AB  - PURPOSE: Multidetector computed tomography (MDCT) is routinely used in the
      diagnosis of pancreatic ductal adenocarcinoma (PDAC), but it may be inadequate in
      some cases, especially mass-forming chronic pancreatitis (MFCP) and
      isoattenuating pancreatic lesions. Perfusion CT (pCT) may help resolve this
      problem. The aim of this study was to evaluate whether pCT could help
      differentiating PDAC from MFCP and in characterization of isoattenuating
      pancreatic lesions. MATERIALS AND METHODS: This prospective study included 89
      cases of pancreatic lesions detected by MDCT and further analyzed with pCT. Sixty
      one cases with final pathological diagnosis PDAC and 12 cases with MFCP were
      included from the study. Blood volume (BV), blood flow (BF), mean transit time
      (MTT), and permeability surface area product (PS) maps were obtained. Perfusion
      values obtained from the lesions and normal parenchyma were compared. RESULTS:
      Compared with normal parenchyma, BV, BF, PS were lower and MTT was longer in PDAC
      and MFCP (p < 0.05). Compared with MFCP, BV, BF, PS were lower and MTT was longer
      in PDAC (p < 0.001). Compared with normal parenchyma, BV, BF, PS were lower and
      MTT was longer in isoattenuating lesions, (p < 0.001). Cutoff values of 7.60
      mL/100 mL, 64.43 mL/100 mL/min, 28.08 mL/100 mL/min for BV, BF, PS, respectively,
      provided 100% sensitivity and specificity and 7.47 s for MTT provided 98.3%
      sensitivity, 80% specificity for distinguishing PDAC from MFCP. CONCLUSION: pCT
      is a useful technology that can be helpful in overcoming the limitations of
      routine MDCT in diagnosing PDAC and characterization of isoattenuating lesions.

PMID- 30225611
TI  - Renal solitary fibrous tumor/hemangiopericytoma: computed tomography findings and
      clinicopathologic features.
AB  - PURPOSE: To retrospectively characterize the clinical, pathological, and computed
      tomography (CT) findings of renal solitary fibrous tumor/hemangiopericytoma
      (rSFT/HPC). METHODS: Twelve patients with rSFT/HPCs were enrolled. The CT
      findings and clinicopathological features were retrospectively reviewed. RESULTS:
      This study included six male and six female patients (median age: 47; age range:
      20-82 years). Eight benign (grade I) and four malignant (grade III) rSFT/HPCs
      were identified. Of the 12 lesions, 10 were in the renal sinus near the renal
      pelvis, while two replaced the whole kidney. Five lesions were well-defined, five
      were partially ill-defined, and two were ill-defined. Mild (5/12) and
      intermediate (1/12) hydronephrosis was observed. On the unenhanced CT images, ten
      tumors showed slightly higher density when compared to the normal renal
      parenchyma, and two masses were isodense to hypodense. After intravenous contrast
      medium injection, three enhancement patterns were observed, including "prolonged
      enhancement" (PE) (6/12), "gradual enhancement" (4/12), and "early washout"
      (2/12). A central fibrous scar was found in five patients. Compared to the grade
      I lesions, the grade III rSFT/HPC lesions tended to be larger (maximal diameter >
      10 cm) and more heterogeneous with a higher incidence of the PE pattern.
      CONCLUSIONS: We have shown that rSFT/HPCs usually arise from the renal sinus, and
      present as lobulated, slightly hyperdense, gradually enhancing soft tissue
      masses. CT findings, including large size, heterogeneity, and the PE pattern, may
      assist in the pre-operative identification of malignant grade III rSFT/HPCs.

PMID- 30225612
TI  - Thymus-specific serine protease, a protease that shapes the CD4 T cell
      repertoire.
AB  - The lifespan of T cells is determined by continuous interactions of their T cell
      receptors (TCR) with self-peptide-MHC (self-pMHC) complexes presented by
      different subsets of antigen-presenting cells (APC). In the thymus, developing
      thymocytes are positively selected through recognition of self-pMHC presented by
      cortical thymic epithelial cells (cTEC). They are subsequently negatively
      selected by medullary thymic epithelial cells (mTEC) or thymic dendritic cells
      (DC) presenting self-pMHC complexes. In the periphery, the homeostasis of mature
      T cells is likewise controlled by the interaction of their TCR with self-pMHC
      complexes presented by lymph node stromal cells while they may be tolerized by DC
      presenting tissue-derived self-antigens. To perform these tasks, the different
      subsets of APC are equipped with distinct combination of antigen processing
      enzymes and consequently present specific repertoire of self-peptides. Here, we
      discuss one such antigen processing enzyme, the thymus-specific serine protease
      (TSSP), which is predominantly expressed by thymic stromal cells. In thymic DC
      and TEC, TSSP edits the repertoire of peptide presented by class II molecules and
      thus shapes the CD4 T cell repertoire.

PMID- 30225614
TI  - Comment on "Characterization of circulating leukocytes and correlation of
      leukocyte subsets with metabolic parameters 1 and 5 years after diabetes
      diagnosis".

PMID- 30225613
TI  - How Heart Rate Should Be Controlled in Patients with Atherosclerosis and Heart
      Failure.
AB  - PURPOSE OF REVIEW: Resting heart rate is an independent risk factor for all-cause
      and cardiovascular mortality in patients with heart failure. The main objectives
      are to discuss the prognosis of heart rate, its association with coronary
      atherosclerosis, and the modalities of control of the heart rate in sinus rhythm
      and in the rhythm of atrial fibrillation in patients with chronic heart failure.
      RECENT FINDINGS: As a therapeutic option for control heart rate, medications such
      as beta-blockers, digoxin, and finally ivabradine have been studied. Non
      dihydropyridine calcium channel blockers are contraindicated in patients with
      heart failure and reduced ejection fraction. The influence of the magnitude of
      heart rate reduction and beta-blocker dose on morbidity and mortality will be
      discussed. Regarding the patients with heart failure and atrial fibrillation,
      there are different findings in heart rate control with the use of a beta
      blocker. Patients eligible for ivabradine have clinical benefits and increased
      ejection fraction. Vagal nerve stimulation has low efficacy for the control of
      heart rate. Complementary therapies such as tai chi and yoga showed no effect on
      heart rate. In this review, we discuss the main therapeutic options for the
      control of heart rate in patients with atherosclerosis and heart failure. More
      research is needed to examine the effects of therapeutic options for heart rate
      control in different population types, as well as their effects on clinical
      outcomes and impact on morbidity and mortality.

PMID- 30225615
TI  - Long-term exposures to ethion and endotoxin cause lung inflammation and induce
      genotoxicity in mice.
AB  - Ethion, an organophosphorus pesticide, is used worldwide and has potential for
      toxicity and inflammation. There are very limited data on the pulmonary and
      genotoxic effects of ethion especially when the exposure is combined with
      lipopolysaccharide. Therefore, we used a mouse model to test the hypothesis that
      prolonged exposure to ethion alone or in conjunction with lipopolysaccharide
      (LPS) will cause lung inflammation and genotoxicity in a mouse model. Swiss
      albino (n = 30) were divided into a control (n = 10) and two treatment groups (n
      = 10; each group). The treatment groups were orally administered ethion (4 or 2
      mg/kg/animal/day; n = 10 each) dissolved in corn oil for 90 days. After 90 days
      of exposure, five animals from each of the groups were challenged with 80 MUg
      Escherichia coli lipopolysaccharide (LPS) intranasally and the remaining five
      animals with normal saline solution via the same route. Ethion at both dosages
      induced lung inflammation as indicated by increased (p < 0.05) perivascular and
      peribronchial accumulation of inflammatory cells along with thickening of the
      alveolar septal wall. Ethion at 4 mg/kg altered (p < 0.05) the mRNA and protein
      expression of TLR-9 and IL-1beta in the lungs and induced genotoxicity in blood
      cells as determined by single cell gel electrophoresis (Comet assay). Further,
      both dosages of ethion in combination with E. coli LPS caused genotoxicity and
      increased (p < 0.05) pulmonary expression of TLR-4, TLR-9 and IL-1beta. The data
      taken together suggest ethion induces lung inflammation and interaction between
      ethion and LPS increases genotoxicity in blood cells.

PMID- 30225617
TI  - Extension of mandatory health insurance to informal sector workers in Togo.
AB  - BACKGROUND: About 90.4% of Togolese workers operate in the informal sector and
      account for between 20 and 30% of Togo's Gross Domestic Product. Despite their
      importance in the Togolese economy, informal sector workers (ISW) do not have a
      health insurance scheme. This paper aims to estimate the willingness-to-pay (WTP)
      of ISW in order to have access to Mandatory Health Insurance (MHI), and to
      analyze the main determinants of WTP. METHODS: This study used data from the
      Community-Based Monitoring System (CBMS) project implemented in 2015 by the
      Partnership for Economic Policy (PEP). It focusses on 4,296 ISW (2,374 in urban
      areas and 1,922 in rural areas, respectively). The contingent valuation method
      was used to determine the WTP for the MHI while the Tobit model is used to
      analyze its determinants. RESULTS AND DISCUSSION: Findings indicate that about
      92% of ISW agreed to have access to MHI, like for formal sector workers. Overall,
      ISW are willing to pay 2,569 FCFA (USD 4.7) per month. ISW in the poorest
      quintiles are willing to allocate a higher proportion of their income (15%) to
      the premium than the richest quintiles (2.5%). Generally, women are more
      interested in MHI than men, although men are willing to pay higher premiums
      (3,168.9 FCFA or USD 5.8) than women (2,077 FCFA or USD 3.8). Women's lower WTP
      can be explained by their low levels of education and income, and a lack of
      employment opportunities compared to men. The gender of the head of the
      household, the size of the household and the education and income levels are the
      main determinants of WTP. CONCLUSION: We conclude that it is possible to extend
      MHI to ISW as long as their premiums are subsidized. The annual subsidy is
      estimated at 4.1% of the state current general budget or 96% of the health sector
      budget. In setting the premium, policy makers should take into account the MHI
      benefits package, subsidies from the government, and information about the WTP.
      It is important to emphasize that resource mobilization and management, as well
      as health services delivery, would be effective only in a context of improved
      governance.

PMID- 30225616
TI  - Translational molecular imaging in exocrine pancreatic cancer.
AB  - Effective treatment for pancreatic cancer remains challenging, particularly the
      treatment of pancreatic ductal adenocarcinoma (PDAC), which makes up more than
      95% of all pancreatic cancers. Late diagnosis and failure of chemotherapy and
      radiotherapy are all too common, and many patients die soon after diagnosis.
      Here, we make the case for the increased use of molecular imaging in PDAC
      preclinical research and in patient management.

PMID- 30225618
TI  - T-Wave Indices and Atherosclerosis.
AB  - Tpeak-Tend interval, the time difference between the peak and the end of the T
      wave, reflects the degree of dispersion of repolarization. Its prolongation has
      been associated with higher risks of developing ventricular arrhythmias and
      sudden cardiac death in different pro-arrhythmic conditions such as Brugada and
      long QT syndromes. In this review, we will provide a comprehensive overview on
      how Tpeak-Tend is altered in different atherosclerotic conditions such as
      hypertension, stable coronary artery disease, acute coronary obstruction, and
      coronary slow flow as well as inflammatory diseases affecting the arterial tree.
      We will explore its relationship with arterial function and dysfunction,
      ventricular remodeling, and arrhythmic and mortality outcomes. The published
      literature shows that patients with coronary atherosclerosis, whether in the form
      of stable coronary artery disease, chronic total occlusion, slow flow, or acute
      coronary obstruction, have prolonged Tpeak-Tend intervals and Tpeak-Tend/QT
      ratios. These can be used to predict the occurrence of ventricular arrhythmias
      and sudden cardiac death. They also correlate with the extent and severity of
      arterial stenosis and structural remodeling of the ventricles as well as arterial
      function and dysfunction. Finally, they can be normalized following
      revascularization and may therefore be used as a surrogate measure of treatment
      success.

PMID- 30225619
TI  - Young age at diagnosis is associated with worse prognosis in the Luminal A breast
      cancer subtype: a retrospective institutional cohort study.
AB  - PURPOSE: Although age is a recognized independent prognostic risk factor, its
      relative importance among molecular subtypes of Breast cancer (BCA) is not well
      documented. The aim of this study was to evaluate the prognostic role of age at
      diagnosis among different immunohistochemical subtypes of BCA. METHODS: We
      conducted a retrospective study of women with invasive BCA undergoing surgery at
      the Johns Hopkins Hospital, excluding patients presenting with stage IV breast
      cancer. Patients were stratified into three age groups: <= 40, 41-60, and > 60
      years, and multivariable analysis was performed using Cox regression. We also
      identified differentially expressed genes (DEG) between age groups among BCA
      subtypes in the public TCGA dataset. Finally, we identified key driver genes
      within the DEGs using a weighted gene co-expression network analysis. RESULTS:
      Luminal A breast cancer patients had significantly lower 5 year disease-free
      survival (DFS) and distant metastasis-free survival (DMFS) in the <= 40 year age
      group compared to the 41-60 year age group, while the other molecular subtypes
      showed no significant association of DFS or DMFS with age. Age was a stronger
      outcome predictor than tumor grade or proliferative index in Luminal A BCA
      patients, but not other subtypes. BCA TCGA gene expression data were divided into
      two groups (<= 40 years, > 40 years). We identified 374 DEGs in the Luminal A BCA
      subset, which were enriched in seven pathways and two modules of co-expressed
      genes. No age group-specific DEGs were identified in non-Luminal A subtypes.
      CONCLUSIONS: Age at diagnosis may be an important prognostic factor in Luminal A
      BCA.

PMID- 30225620
TI  - Prognosis in patients diagnosed with loco-regional failure of breast cancer: 34
      years longitudinal data from the Stockholm-Gotland cancer registry.
AB  - RATIONALE: Survival after loco-regional failure (LRF) of breast cancer was
      investigated at the population level. METHODS: Using the Stockholm cancer
      registry, 2698 patients diagnosed with LRF between 1980 and 2014 were identified
      and divided into three cohorts by year of LRF diagnosis. Post-relapse event-free
      survival (EFS) and overall survival (OS) were analyzed separately in local and
      loco-regional relapses and compared across the cohorts by Kaplan-Meier method.
      Relative survival was estimated and Poisson regression models, adjusted for
      clinically relevant prognostic factors, were fitted for excess mortality ratio
      calculation. Age-related survival trends were also explored. RESULTS: Among 1922
      patients diagnosed with local relapse, 1032 (54%) EFS events and 931 (48%) deaths
      were registered. A significant improvement in EFS (p < 0.001) and OS (p < 0.001)
      was demonstrated in tumors that recurred locally in the years 1990-1999 and 2000
      2014 compared with 1980-1989, regardless of age at relapse (<= 60 years; > 60
      years). In women with loco-regional relapse, 557 out of 776 (72%) experienced a
      post-relapse event and 522 (67%) died. Significantly longer EFS and OS were seen
      over time in the whole group (p < 0.001 and p = 0.003, respectively) and in
      younger (p < 0.001; p < 0.001) but not in older women (p = 0.55; p = 0.80).
      Relative survival was consistent with OS and a statistically significant decrease
      in mortality after loco-regional recurrence over time was seen only in women aged
      <= 60 years. CONCLUSIONS: Survival after loco-regional failure of breast cancer
      has improved over time, especially in younger women.

PMID- 30225622
TI  - A hybrid data envelopment analysis and game theory model for performance
      measurement in healthcare.
AB  - Performance measurement plays an important role in the successful design and
      reform of regional healthcare management systems. In this study, we propose a
      hybrid data envelopment analysis (DEA) and game theory model for measuring the
      performance and productivity in the healthcare centers. The input and output
      variables associated with the efficiency of the healthcare centers are identified
      by reviewing the relevant literature, and then used in conjunction with the
      internal organizational data. The selected indicators and collected data are then
      weighted and prioritized with the help of experts in the field. A case study is
      presented to demonstrate the applicability and efficacy of the proposed model.
      The results reveal useful information and insights on the efficiency levels of
      the regional healthcare centers in the case study.

PMID- 30225621
TI  - Micro-computed tomography enables rapid surgical margin assessment during breast
      conserving surgery (BCS): correlation of whole BCS micro-CT readings to final
      histopathology.
AB  - BACKGROUND: Roughly 23% of breast conserving surgery (BCS) patients undergo a
      second re-excision procedure due to pathologically positive surgical margins. We
      investigated the feasibility and potential value of micro-Computed Tomography
      (micro-CT) as a surgical margin guidance tool during BCS. METHODS: A cohort of 32
      BCS specimens was prospectively imaged with a pre-clinical micro-CT system upon
      arrival in the surgical pathology laboratory. Reconstructed micro-CT scans were
      evaluated retrospectively by an experienced breast radiologist, who provided
      binary determinations whether lesions extended to the specimen margin. These
      readings were then compared to the final pathological diagnosis and to 2D
      specimen radiography readings. RESULTS: Of the 32 specimens imaged, 28 had
      malignant and four had benign pathological diagnoses. Overall five (four
      malignant, one benign) of the 32 specimens had lesion tissue extending to the
      margin. For all 32 specimens, micro-CT reconstructions were calculated (< 4 min.
      acquisition + reconstruction time) and each specimen was volumetrically analyzed
      by a radiologist. Of the 28 malignant specimen readings, 18 matched the final
      pathological diagnosis [64%, 95 CI (47%-81%)], with a negative predictive value
      of 89% [95 CI (74%-96%)]. Micro-CT readings revealed changes in the tumor
      location and margin status as compared to single-projection radiography readings.
      CONCLUSIONS: Micro-CT scanning of BCS specimens enabled margin status assessment
      over the entirety of the surgical surface in a clinically relevant time frame,
      provided additional spatial information over single-projection radiography, and
      may be a potentially useful BCS guidance tool.

PMID- 30225623
TI  - Correction to: ECDC definitions and methods for the surveillance of healthcare
      associated infections in intensive care units.
AB  - The article ECDC definitions and methods for the surveillance of healthcare
      associated infections in intensive care units.

PMID- 30225624
TI  - Correction to: White paper: statement on conflicts of interest.
AB  - The original version of this article unfortunately contained a mistake.

PMID- 30225625
TI  - Correction to: Iron metabolism in diabetes-induced Alzheimer's disease: a focus
      on insulin resistance in the brain.
AB  - Due to a technical error, the copyright line of the above mentioned article was
      incorrect. The original publication has been corrected.

PMID- 30225626
TI  - Suicide Prevention is Everyone's Business.
AB  - ?.

PMID- 30225628
TI  - Sleep quality in survivors of critical illness: practical shortcomings resolved.

PMID- 30225629
TI  - The amounts and contributions of total drinking fluids and water from food to
      total water intake of young adults in Baoding, China.
AB  - PURPOSE: To investigate the amounts and contributions of total drinking fluids
      and water from food to total water intake (TWI), to explore the drinking pattern,
      and to compare the amount of TWI with the recommendations of China and EFSA among
      young adults. METHODS: A cross-sectional study was implemented with 159 young
      adults aged 18-23 years from Hebei, China. Total drinking fluids and water from
      food were assessed by 7-day 24-h fluid intake questionnaire and the duplicate
      portion method, respectively. Differences between groups stratified according to
      the distribution of TWI were compared using one-way ANOVA and Kruskal-Wallis H
      test. General linear models were used to identify the variations in TWI due to
      total drinking fluids and water from food. RESULTS: In total, 156 subjects (80
      males and 76 females) completed the study. Approximately 80.1% of them did not
      meet the TWI recommended by China, while 50.0% did not meet that recommended by
      the EFSA. Participants with higher TWI had greater amounts of total drinking
      fluids, water rom food and water than their counterparts with lower TWI. The
      regression between total drinking fluids and TWI was R2 = 0.8526 (P < 0.05) and
      that between water from food and TWI was R2 = 0.4650 (P < 0.05). CONCLUSIONS: A
      large proportion of young adults have insufficient TWI. Participants with lower
      TWI would not compensate with water from food. The variances in TWI among
      participants were mainly due to differences in total drinking fluids. There is an
      urgent need to improve the fluids intake behaviors of young adults.

PMID- 30225630
TI  - Substitution of red meat with poultry or fish and risk of type 2 diabetes: a
      Danish cohort study.
AB  - PURPOSE: We examined associations between substitution of red meat (total,
      processed and unprocessed, low fat and high fat) with poultry or fish and
      substitution of processed red meat with unprocessed red meat and the risk of type
      2 diabetes. METHODS: A cohort of 53,163 participants from the Danish Diet, Cancer
      and Health study were followed for incident type 2 diabetes (6879 cases; median
      follow-up time 15.4 years). Diet was assessed by a validated 192-item food
      frequency questionnaire at baseline. Adjusted Cox proportional hazard models were
      used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for type 2
      diabetes associated with specified food substitutions of 150 g/week. RESULTS:
      Replacing total red meat with fish was associated with a lower risk of type 2
      diabetes [HR 0.96 (95% CI 0.94, 0.99)] as was replacement of processed red meat
      with poultry or fish [HR poultry 0.96 (95% CI 0.93, 0.99)]; HR fish 0.94 [(95% CI
      0.91, 0.97)]. Replacing low fat red meat or high fat red meat with fish was
      associated with a lower risk of type 2 diabetes whereas similar substitutions,
      with poultry, were not. Replacing processed red meat with unprocessed red meat
      was also associated with a lower risk of type 2 diabetes [HR 0.96 (95% CI 0.93,
      0.99)]. CONCLUSIONS: Replacing processed red meat with poultry, replacing total
      or processed red meat with fish, and replacing processed red meat with
      unprocessed red meat were all associated with a lower risk of type 2 diabetes.

PMID- 30225631
TI  - Commentary on: Urinary symptoms are associated with certain urinary microbes in
      urogynecologic surgical patients.

PMID- 30225632
TI  - Correction to: Meningomyeloradiculitis following yellow fever 17D vaccination: a
      case report.
AB  - There was an error in the original article. In the last paragraph of the Case
      Report section, the sentence "One month later, two plasma exchanges were followed
      by only slight improvements in upper-limb motor function (Fig. 1)." should have
      been "One month later, four plasma exchanges were followed.

PMID- 30225627
TI  - Targeting the Muscle-Bone Unit: Filling Two Needs with One Deed in the Treatment
      of Duchenne Muscular Dystrophy.
AB  - PURPOSE OF REVIEW: In Duchenne muscular dystrophy (DMD), the progressive skeletal
      and cardiac muscle dysfunction and degeneration is accompanied by low bone
      mineral density and bone fragility. Glucocorticoids, which remain the standard of
      care for patients with DMD, increase the risk of developing osteoporosis. The
      scope of this review emphasizes the mutual cohesion and common signaling pathways
      between bone and skeletal muscle in DMD. RECENT FINDINGS: The muscle-bone
      interactions involve bone-derived osteokines, muscle-derived myokines, and dual
      origin cytokines that trigger common signaling pathways leading to fibrosis,
      inflammation, or protein synthesis/degradation. In particular, the triad
      RANK/RANKL/OPG including receptor activator of NF-kB (RANK), its ligand (RANKL),
      along with osteoprotegerin (OPG), regulates bone matrix modeling and remodeling
      pathways and contributes to muscle pathophysiology in DMD. This review discusses
      the importance of the muscle-bone unit in DMD and covers recent research aimed at
      determining the muscle-bone interactions that may eventually lead to the
      development of multifunctional and effective drugs for treating muscle and bone
      disorders regardless of the underlying genetic mutations in DMD.

PMID- 30225633
TI  - [The TraumaRegister DGU(r) dataset, its development over 25 years and advances in
      the care of severely injured patients].
AB  - BACKGROUND: Since the publication in 1993, the dataset and documentation form of
      the TraumaRegister DGU(r) (TR-DGU) have continuously evolved. On the occasion of
      the 25th anniversary the authors have analyzed this evolution in order to reflect
      it in the light of medical progress in the treatment of the severely injured.
      MATERIAL AND METHODS: Enrolled in the study were 5 reference data entry sheets
      from the years 1993, 1996, 2002, 2009 and 2016. Every piece of information (item)
      queried therein was entered into the study database, was categorized by topic and
      counted for further analysis. RESULTS: The arrangement of the 4-page data entry
      form has remained practically unchanged since 1993 and includes an average of 212
      items. A total of 491 items were identified of which 64 were present throughout
      every dataset. Based on the average extent of the form this equals a proportion
      of approximately 30%. The dataset actually shows much more consistency than this
      number suggests because many changes can be traced back to a smarter design of
      the data entry form. Most items fell into the categories "results/diagnosis" (143
      items/29.1%), "coagulation" (104/21.2%) and "surgical approach" (40/8.1%). Many
      items serve as raw data for the calculation of prognostic risk scores, such as
      the trauma and injury severity score (TRISS), the revised injury severity
      classification II (RISC II) and the trauma associated severe hemorrhage (TASH)
      score. Currently, nine scores can be calculated from the dataset. CONCLUSION: The
      members of the working group TraumaRegister all actively participate in the
      treatment of severely injured patients. For 25 years this group has managed to
      unify the latest medical developments and well-established parameters within the
      TR-DGU dataset at a relatively constant degree of effort for documentation.
      Practice in place of theory is the driving force behind this development that
      serves quality assurance and research in the treatment of severely injured
      patients.

PMID- 30225634
TI  - Individual screening strategy for pediatric celiac disease.

PMID- 30225635
TI  - What can we learn from unaccompanied refugee adolescents' perspectives on mental
      health care in exile?
AB  - Unaccompanied refugee adolescents who have fled war and persecution often have
      poor mental health. Yet, little is known about their own perspectives on what can
      relieve their mental health problems. The aim was to explore unaccompanied
      refugee adolescents' perspectives on healing and the mental healthcare offered to
      them when resettled. The study was based on methodical triangulation of
      participant observation in a Danish municipal institution for unaccompanied
      refugee minors, semi-structured individual interviews with experts, social
      workers and male refugee minors and a focus group interview with refugee minors.
      Results show that the refugee adolescents associated traditional conversational
      therapy with discussing negative and stigmatising aspects of their past and
      carrying risks of re-traumatisation. Instead, alternative activities were
      proposed, through which resources could be accumulated and they could be met
      without stereotype.Conclusion: To enhance the complex mental health needs of
      unaccompanied minors' mental healthcare, the perspective of the refugee
      adolescents should be taken into account. This calls for a holistic approach to
      mental healthcare in their daily lives, where they are met in a non-stigmatising
      manner in which their unique capabilities are the main focus. Moreover, a
      trusting relationship constitutes the fundament to support good mental health
      among refugee adolescents. What is Known: * Unaccompanied refugee adolescents are
      at risk of poor mental health outcomes, e.g., depression, anxiety, PTSD and
      psychosocial stress. * Stigma, lack of social support, stressful life events and
      lack of intercultural competency among mental health professionals are barriers
      to good mental health. What is New: * There is a need for informal and tailored
      health promotion initiatives in the refugee adolescents' everyday lives. * To
      treat the refugee adolescents as equal human beings through curiosity and
      receptiveness to their resources is important in order to build trust and address
      stigma.

PMID- 30225636
TI  - Assessment of clinical outcome of children with sepsis outside the intensive care
      unit.
AB  - In 2016, in order to identify adult patients with sepsis who are likely to have
      poor outcomes, the Third International Consensus Definitions Task Force
      introduced a new bedside index, called the quick Sepsis-related Organ Failure
      Assessment (qSOFA) score. However, these new criteria have not been validated in
      the pediatric population. In this study, we sought to assess the qSOFA score for
      children with sepsis, who are being treated outside the pediatric intensive care
      units. The qSOFA criteria were revised and applied to a study population of 89
      pediatric patients with sepsis, admitted in a pediatric tertiary referral center
      from 2006 to 2016. The analysis of prognostic performance of qSOFA score for the
      prediction of severe sepsis showed a sensitivity of 46% (95% CI, 27-67%), a
      specificity of 74% (95% CI, 62-85%), a positive predictive value of 43% (95% CI,
      34-52%), and a negative predictive value of 77% (95% CI, 71-82%). The area under
      ROC curve for qSOFA score >= 2 was 0.602 (95% CI 0.492-0.705).Conclusion: The
      qSOFA score showed a low accuracy to identify children in the pediatric ward at
      risk for severe sepsis. Clinical tools are needed to facilitate the diagnosis of
      impending organ dysfunction in pediatric infection outside of the ICU. What is
      Known: * One of the major challenges for clinicians is to identify and recognize
      children with sepsis and impending organ dysfunction, in the emergency and in the
      pediatric department. * In 2016, members of the Sepsis-3 task force proposed
      qSOFA, an empirically derived score using simple clinical criteria, to assist
      clinicians in identifying adult patients with sepsis at risk for poor outcome.
      What is New: * qSOFA demonstrated insufficient clinical value to be recommended
      as a screening tool for pediatric sepsis outside ICU. * D-dimer level and blood
      glucose may be useful biomarkers to identify children at risk for severe sepsis.

PMID- 30225638
TI  - Fluoride induces apoptosis and autophagy through the IL-17 signaling pathway in
      mice hepatocytes.
AB  - Previous studies have reported that excessive fluoride exposure induced liver
      damage. However, the underlying mechanism of fluoride-induced hepatic toxicity is
      still unclear. Hence, this study was aimed to evaluate the fluoride-induced
      apoptosis, autophagy, and IL-17 signaling pathway-related genes to explore the
      possible mechanisms of NaF-induced liver injury in mice. For this, 48 male mice
      were allotted randomly to four groups, treated with deionized water, 25, 50, 100
      mg/L NaF for 150 days continuously. Our results suggested that treatment with NaF
      decreased the PAS staining-positive area, with a concomitant increase in liver
      score, and serum ALT and AST levels which indicated that NaF induced the liver
      injury. In addition, the qRT-PCR, immunohistochemistry, and western blotting
      results indicated that NaF exposure activated IL-17 signaling, apoptosis, and
      autophagy pathways. In summary, these results suggested that NaF induced
      apoptosis and autophagy in liver by activating the IL-17 signaling pathway,
      eventually leading to impaired liver function.

PMID- 30225637
TI  - 3,3'-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat
      cortical neurons via a CREB-dependent mechanism.
AB  - PCB 11 (3,3'-dichlorobiphenyl), a contemporary congener produced as a byproduct
      of current pigment production processes, has recently emerged as a prevalent
      worldwide pollutant. We recently demonstrated that exposure to PCB 11 increases
      dendritic arborization in vitro, but the mechanism(s) mediating this effect
      remain unknown. To address this data gap, primary cortical neuron-glia co
      cultures derived from neonatal Sprague-Dawley rats were exposed for 48 h to
      either vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM
      in the absence or presence of pharmacologic antagonists of established molecular
      targets of higher chlorinated PCBs. Reporter cell lines were used to test
      activity of PCB 11 at the aryl hydrocarbon receptor (AhR) and thyroid hormone
      receptor (THR). PCB 11 lacked activity at the AhR and THR, and antagonism of
      these receptors had no effect on the dendrite-promoting activity of PCB 11.
      Pharmacologic antagonism of various calcium channels or treatment with
      antioxidants also did not alter PCB 11-induced dendritic arborization. In
      contrast, pharmacologic blockade or shRNA knockdown of cAMP response element
      binding protein (CREB) significantly decreased dendritic growth in PCB 11-exposed
      cultures, suggesting PCB 11 promotes dendritic growth via CREB-mediated
      mechanisms. Since CREB signaling is crucial for normal neurodevelopment, and
      perturbations of CREB signaling have been associated with neurodevelopmental
      disorders, our findings suggest that this contemporary pollutant poses a threat
      to the developing brain, particularly in individuals with heritable mutations
      that promote CREB signaling.

PMID- 30225639
TI  - Arsenic induces autophagy in developmental mouse cerebral cortex and hippocampus
      by inhibiting PI3K/Akt/mTOR signaling pathway: involvement of blood-brain
      barrier's tight junction proteins.
AB  - For the past decade, there has been an increased concern about the health risks
      from arsenic (As) exposure, because of its neurotoxic effects on the developing
      brain. The exact mechanism underlying As-induced neurotoxicity during sensitive
      periods of brain development remains unclear, especially the role of blood-brain
      barrier's (BBB) tight junction (TJ) proteins during As-induced neurotoxicity.
      Here, we highlight the involvement of TJ proteins in As-induced autophagy in
      cerebral cortex and hippocampus during developmental periods [postnatal day (PND)
      21, 28, 35 and 42]. Here, the administration of arsenic trioxide (As2O3) at doses
      of 0.15 mg or 1.5 mg or 15 mg As2O3/L in drinking water from gestational to
      lactational and continued to the pups till PND42 resulted in a significant
      decrease in the mRNA expression levels of TJ proteins (Occludin, Claudin, ZO-1
      and ZO-2) and Occludin protein expression level. In addition, As exposure
      significantly decreased PI3K, Akt, mTOR, and p62 with a concomitant increase in
      Beclin1, LC3I, LC3II, Atg5 and Atg12. Moreover, As exposure also significantly
      downregulated the protein expression levels of mTOR with a concomitant
      upregulation of Beclin 1, LC3 and Atg12 in all the developmental age points.
      However, no significant alterations were observed in low and medium dose-exposed
      groups of PND42. Histopathological analysis in As-exposed mice revealed decreased
      number of pyramidal neurons in hippocampus; and neurons with degenerating axons,
      shrinkage of cells, remarkable vacuolar degeneration in cytoplasm, karyolysis and
      pyknosis in cerebral cortex. Ultrastructural analysis by transmission electron
      microscopy revealed the occurrence of autophagosomes and vacuolated axons in the
      cerebral cortex and hippocampus of the mice exposed to high dose As at PND21 and
      42. The severities of changes were found to more persist in the cerebral cortex
      than in the hippocampus of As-exposed mice. Finally, we conclude that the leaky
      BBB in cerebral cortex and hippocampus may facilitate the transfer of As and
      induces autophagy by inhibiting PI3K/Akt/mTOR signaling pathway in an age
      dependent manner, i.e., among the four different developmental age points, PND21
      animals were found to be more vulnerable to the As-induced neurotoxicity than the
      other three age points.

PMID- 30225640
TI  - Determination of the Pharmacokinetics and Tissue Distribution of Methyl 3,4
      Dihydroxybenzoate (MDHB) in Mice Using Liquid Chromatography-Tandem Mass
      Spectrometry.
AB  - BACKGROUND AND OBJECTIVES: Methyl 3,4-dihydroxybenzoate (MDHB) has the potential
      to prevent neurodegenerative diseases (NDDs). The present work aims to reveal the
      pharmacokinetics and tissue distribution characteristics of MDHB. METHODS: The
      pharmacokinetics and tissue distribution of MDHB were analyzed using LC-MS/MS
      after a single intragastric administration (50 to 450 mg/kg) in mice, and samples
      were collected from five animals at specific time points. RESULTS:
      Pharmacokinetic parameters of MDHB following intragastric administrations were:
      the time to peak concentration (Tmax) ranged from 0.033 to 0.07 h, the peak
      concentration (Cmax) ranged from 12,379.158 to 109798.712 MUg/l, the elimination
      half-life (t1/2z) ranged from 0.153 to 1.291 h, the area under the curve (AUC0
      infinity) ranged from 640.654 to 20,241.081 MUg/l * h, the mean residence time
      (MRT0-infinity) ranged from 0.071 to 0.206 h, the apparent volume of distribution
      (Vz/F) ranged from 17.538 to 45.244 l/kg, and the systemic clearance (Clz/F)
      ranged from 22.541 to 80.807 l/h/kg. The oral bioavailability of MDHB was 23%.
      The maximum MDHB content was detected in the stomach, and the minimum content was
      observed in the testes; the peak content in the brain was 15,666.93 ng/g.
      CONCLUSIONS: The pharmacokinetic characteristics of MDHB include fast absorption,
      high systemic clearance, a short half-life and an oral bioavailability of 23%.
      Additionally, MDHB permeates the blood-brain barrier (BBB) and is rapidly
      distributed to all organs. The identification of the pharmacokinetics of MDHB
      following its oral administration will contribute to further preclinical and
      clinical studies of its effects.

PMID- 30225641
TI  - Fine mapping Ruv2, a new rust resistance gene in cowpea (Vigna unguiculata), to a
      193-kb region enriched with NBS-type genes.
AB  - KEY MESSAGE: A new rust resistance gene Ruv2 was fine-mapped in cowpea to a 193
      kb region on chromosome 2, which harboured 23 predicted gene models enriched with
      NBS-type genes. ZN016 is a landrace vegetable cowpea highly resistant to rust.
      Two previous studies using mixed-spores inoculation suggested different modes of
      inheritance of rust resistance in ZN016. In this study, we initially developed a
      detached leaf assay with a purified single-rust isolate (Auv-LS). Using this
      approach, we assessed the inheritance of rust resistance in a recombinant inbred
      line (RIL) population and an F2 population, both derived from the cross of
      "ZN016" and the susceptible cultivar "Zhijiang282." A single dominant gene mode
      against Auv-LS was revealed in both populations. QTL mapping showed that this
      gene was coincident with the Ruv2 locus on LG7, one of the three resistance QTLs
      previously mapped based on mixed-spores inoculation data. Therefore, Ruv2 was
      considered as specifically against the rust isolate Auv-LS. Through an analysis
      of the RIL recombinants at Ruv2, we fine-mapped the gene to an ~ 0.45-cM interval
      between SNP markers 2_09656 and 2_00973, which corresponded to an ~ 193-kb region
      on chromosome 2 that harboured 23 predicted gene models enriched with NBS-type
      genes. Re-sequencing of the two parents revealed polymorphisms in four genes
      predictively to cause substantial protein structural changes, rendering them
      valuable candidate genes for future validation. Cross-species syntenic analysis
      indicated that Ruv2 may represent a novel rust resistance gene in food legumes. A
      cleaved amplified polymorphic sequences marker tightly linked to Ruv2 was
      developed to facilitate breeding. This work establishes a basis for map-based
      cloning of Ruv2 and breeding for rust resistance in cowpea and other legume
      crops.

PMID- 30225642
TI  - Identification of novel recessive gene xa44(t) conferring resistance to bacterial
      blight races in rice by QTL linkage analysis using an SNP chip.
AB  - KEY MESSAGE: Using QTL analysis and fine mapping, the novel recessive gene
      xa44(t) conferring resistance to BB was identified and the expression level of
      the gene was confirmed through qRT-PCR analysis. Bacterial blight (BB) disease
      caused by Xanthomonas oryzae pv. oryzae (Xoo) is a major factor causing rice
      yield loss in most rice-cultivating countries, especially in Asia. The deployment
      of cultivars with resistance to BB is the most effective method to control the
      disease. However, the evolution of new Xoo or pathotypes altered by single-gene
      dependent mutations often results in breakdown of resistance. Thus, efforts to
      identify novel R-genes with sustainable BB resistance are urgently needed. In
      this study, we identified three quantitative trait loci (QTLs) on chromosomes 1,
      4, and 11, from an F2 population of 493 individuals derived from a cross between
      IR73571-3B-11-3-K3 and Ilpum using a 7K SNP chip. Of these QTLs, one major QTL,
      qBB_11, on chromosome 11 explained 61.58% of the total phenotypic variance in the
      population, with an LOD value of 113.59, based on SNPs 11964077 and 11985463. The
      single major R-gene, with recessive gene action, was designated xa44(t) and was
      narrowed down to a 120-kb segment flanked within 28.00 Mbp to 28.12 Mbp. Of nine
      ORFs present in the target region, two ORFs revealed significantly different
      expression levels of the candidate genes. These candidate genes (Os11g0690066 and
      Os11g0690466) are described as "serine/threonine protein kinase domain containing
      protein" and "hypothetical protein," respectively. The results will be useful to
      further understand BB resistance mechanisms and provide new sources of
      resistance, together with DNA markers for MAS breeding to improve BB resistance
      in rice.

PMID- 30225643
TI  - The western Mediterranean region provided the founder population of domesticated
      narrow-leafed lupin.
AB  - KEY MESSAGE: This study revealed that the western Mediterranean provided the
      founder population for domesticated narrow-leafed lupin and that genetic
      diversity decreased significantly during narrow-leafed lupin domestication. The
      evolutionary history of plants during domestication profoundly shaped the genome
      structure and genetic diversity of today's crops. Advances in next-generation
      sequencing technologies allow unprecedented opportunities to understand genome
      evolution in minor crops, which constitute the majority of plant domestications.
      A diverse set of 231 wild and domesticated narrow-leafed lupin (Lupinus
      angustifolius L.) accessions were subjected to genotyping-by-sequencing using
      diversity arrays technology. Phylogenetic, genome-wide divergence and linkage
      disequilibrium analyses were applied to identify the founder population of
      domesticated narrow-leafed lupin and the genome-wide effect of domestication on
      its genome. We found wild western Mediterranean population as the founder of
      domesticated narrow-leafed lupin. Domestication was associated with an almost
      threefold reduction in genome diversity in domesticated accessions compared to
      their wild relatives. Selective sweep analysis identified no significant
      footprints of selection around domestication loci. A genome-wide association
      study identified single nucleotide polymorphism markers associated with pod
      dehiscence. This new understanding of the genomic consequences of narrow-leafed
      lupin domestication along with molecular marker tools developed here will assist
      plant breeders more effectively access wild genetic diversity for crop
      improvement.

PMID- 30225644
TI  - Low molecular weight glutenin subunit gene composition at Glu-D3 loci of Aegilops
      tauschii and common wheat and a further view of wheat evolution.
AB  - KEY MESSAGE: A comprehensive comparison of LMW-GS genes between Ae. tauschii and
      its progeny common wheat. Low molecular weight glutenin subunits (LMW-GSs) are
      determinant of wheat flour processing quality. However, the LMW-GS gene
      composition in Aegilops tauschii, the wheat D genome progenitor, has not been
      comprehensively elucidated and the impact of allohexaploidization on the Glu-D3
      locus remains elusive. In this work, using the LMW-GS gene molecular marker
      system and the full-length gene-cloning method, LMW-GS genes at the Glu-D3 loci
      of 218 Ae. tauschii and 173 common wheat (Triticum aestivum L.) were
      characterized. Each Ae. tauschii contained 11 LMW-GS genes, and the whole
      collection was divided into 25 haplotypes (AeH01-AeH25). The Glu-D3 locus in
      common wheat lacked the LMW-GS genes D3-417, D3-507 and D3-552, but shared eight
      genes of identical open reading frame (ORF) sequences when compared to that of
      Ae. tauschii. Therefore, the allohexaploidization induces deletions, but exerts
      no influence on LMW-GS gene coding sequences at the Glu-D3 locus. 92.17% Ae.
      tauschii had 7-9 LMW-GSs, more than the six subunits in common wheat. The
      haplotypes AeH16, AeH20 and AeH23 of Ae. tauschii ssp. strangulate distributed in
      southeastern Caspian Iran were the main putative D genome donor of common wheat.
      These results facilitate the utilization of the Ae. tauschii glutenin gene
      resources and the understanding of wheat evolution.

PMID- 30225645
TI  - Imaging findings of sterile pyogenic arthritis, pyoderma gangrenosum and acne
      (PAPA) syndrome: differential diagnosis and review of the literature.
AB  - Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is a rare
      autosomal-dominant autoinflammatory disease of incomplete penetrance and variable
      expression. PAPA syndrome is the result of a mutation in the proline serine
      threonine phosphatase-interacting protein 1 (PSTPIP1/CD2BP1) gene located on
      chromosome 15, which results in an abnormal overproduction of the pro
      inflammatory cytokine interleukin-1beta (IL-1). This syndrome clinically
      manifests as early onset of recurrent episodes of acute aseptic inflammation of
      the joints, generally occurring in the first two decades of life, followed by
      manifestation of characteristic skin lesions in the third decade, after an
      obvious decline in the joint symptoms. Although uncommon, the potential clinical
      implications of PAPA syndrome warrant an appropriate diagnosis in a timely
      fashion.

PMID- 30225646
TI  - [White papules on forehead, cheeks and retroauricular area].

PMID- 30225647
TI  - Transgenic mice with a tandem duplication of the Necdin gene overexpress Necdin.
AB  - Necdin (Ndn) transgenic (Tg) mice were generated with a bacterial artificial
      chromosome (BAC) clone. Droplet digital PCR (ddPCR) and inverse PCR methods
      revealed that the transgene consisted of four fragments with a total length of
      171 kb. Two of these fragments were tandem tail-to-tail duplicates of 77 kb and
      37 kb that both contained a Ndn gene. The transgene was inserted in chromosome
      15qD1. Ndn is a paternally expressed imprinted gene; however, the total
      expression level of Ndn in hemizygous Tg mice was approximately twofold higher
      than that in wild-type mice. ddPCR assays with locked nucleic acid (LNA) TaqMan
      probes revealed that transgenic Ndn expression was almost equal to endogenous Ndn
      expression, despite there being two copies of the Ndn gene in the transgene,
      indicating an interaction between the transcriptional regulation of endogenous
      Ndn and the transgene. ddPCR assays with LNA TaqMan probes were also applied for
      imprinting analysis to confirm exclusive paternal expression in tissues with low
      Ndn expression. This is the first report of a Tg mouse with a tandem duplication
      of a Ndn transgene and Ndn overexpression, which will be useful for the in vivo
      study of Ndn overexpression and for rescue experiments of the neonatal lethality
      seen in the Ndn knockout mouse.

PMID- 30225648
TI  - Lessons learnt from the Tasmanian devil facial tumour regarding immune function
      in cancer.
AB  - Genetic and genomic technologies have facilitated a greater understanding of the
      Tasmanian devil immune system and the origins, evolution and spread of devil
      facial tumour disease (DFTD). DFTD is a contagious cancer that has caused
      significant declines in devil populations across Tasmania. Immune responses to
      DFTD are rarely detected, allowing the cancer to pass between individuals and
      proliferate unimpeded. Early immunosenscence in devils appears to decrease anti
      tumour immunity in older animals compared to younger animals, which may increase
      susceptibility to DFTD and explain high DFTD prevalence in this age group. Devils
      also have extremely low major histocompatibility complex (MHC) diversity, and
      multiple alleles are shared with the tumour, lowering histocompatibility barriers
      which may have contributed to DFTD evolution. DFTD actively evades immune attack
      by down-regulating cell-surface MHC I molecules, making it effectively invisible
      to the immune system. Altered MHC I profiles should activate natural killer (NK)
      cell anti-tumour responses, but these are absent in DFTD infection. Recent
      immunisation and immunotherapy using modified DFTD cells has induced an anti-DFTD
      immune response and regression of DFTD in some devils. Knowledge gained from
      immune responses to a transmissible cancer in devils will ultimately reveal
      useful insights into immunity to cancer in humans and other species.

PMID- 30225650
TI  - Gender differences and lung cancer risk in occupational chefs: analyzing more
      than 350,000 chefs in Taiwan, 1984-2011.
AB  - OBJECTIVES: Cooking oil fumes (COFs) contain many carcinogens. We investigated
      the association between COFs and incidence risk of any cancer and lung cancer in
      chefs. METHODS: We identified Chinese food chefs and non-Chinese food chefs from
      Taiwan's national database of certified chefs in 1984-2007. Of them, 379,275 had
      not been diagnosed as having any cancer before chef certification. We followed
      them in Taiwan's Cancer Registry Database (1979-2010) and Taiwan's National Death
      Statistics Database (1985-2011) for any newly diagnosed cancer or lung cancer.
      RESULTS: 378,126 and 379,215 chefs were included for risk analysis of cancer and
      lung cancer, respectively. 6099 chefs developed cancer and 339 developed lung
      cancer over the follow-up periods of 4,183,550 and 4,220,163 person-years,
      respectively. Compared to non-Chinese food chefs, the adjusted IRR of cancer for
      Chinese food chefs was 1.69 (95% CI 1.51-1.89). For lung cancer, the risk was
      significantly higher among Chinese food chefs who had been certified for more
      than 5 years (adjusted IRR 2.12, 95% CI 1.32-3.40). This increased risk was
      pronounced in female chefs (adjusted IRR 4.73, 95% CI 1.74-12.86). CONCLUSIONS:
      Chinese food chefs had an increased risk of cancer and lung cancer, particularly
      in females.

PMID- 30225649
TI  - Using Human Plasma as an Assay Medium in Caco-2 Studies Improves Mass Balance for
      Lipophilic Compounds.
AB  - PURPOSE: To examine the utility of human plasma as an assay medium in Caco-2
      permeability studies to overcome poor mass balance and inadequate sink conditions
      frequently encountered with lipophilic compounds. METHODS: Caco-2 permeability
      was assessed for reference compounds with known transport mechanisms using either
      pH 7.4 buffer or human plasma as the assay medium in both the apical and
      basolateral chambers. When using plasma, Papp values were corrected for the
      unbound fraction in the donor chamber. The utility of the approach was assessed
      by measuring the permeability of selected antimalarial compounds using the two
      assay media. RESULTS: Caco-2 cell monolayer integrity and P-gp transporter
      function were unaffected by the presence of human plasma in the donor and
      acceptor chambers. For many of the reference compounds having good mass balance
      with buffer as the medium, higher Papp values were observed with plasma, likely
      due to improved acceptor sink conditions. The lipophilic antimalarial compounds
      exhibited low mass balance with buffer, however the use of plasma markedly
      improved mass balance allowing the determination of more reliable Papp values.
      CONCLUSIONS: The results support the utility of human plasma as an alternate Caco
      2 assay medium to improve mass balance and permeability measurements for
      lipophilic compounds.

PMID- 30225651
TI  - Low-Grade Serous Ovarian Cancer: Current Treatment Paradigms and Future
      Directions.
AB  - OPINION STATEMENT: Low-grade serous ovarian cancer (LGSOC) is a rare subtype of
      ovarian cancer, accounting for approximately 10% of cases of serous ovarian
      cancer. Patients typically present at a younger age have a protracted clinical
      course with survival for those with recurrent disease nearing 10 years, and have
      a high prevalence of somatic (tumor-specific) mutations affecting the mitogen
      activated protein kinase (MAPK) pathway. Initial treatment of patients with stage
      IC-IV disease is similar to that of high-grade serous ovarian cancer with surgery
      and platinum/taxane-based chemotherapy. Selected patients may benefit from
      hormonal maintenance therapy following chemotherapy, in particular those with
      evidence of residual disease at completion of therapy. In the recurrent setting,
      the highest response rates to chemotherapy have been noted in those patients
      receiving chemotherapy in combination with bevacizumab. While hormonal therapies
      may offer disease stabilization with relatively low toxicity, objective response
      rates remain low. The use of targeted therapies such as MEK inhibitors remains an
      active area of investigation and those patients with MAPK pathway alterations may
      derive the greatest benefit from these agents.

PMID- 30225652
TI  - Facile One-Pot Synthesis of Polydopamine Carbon Dots for Photothermal Therapy.
AB  - Carbon dots (CDs) are a member of fluorescent carbon nanomaterials that are
      widely applied in bioimaging, photothermal therapy (PTT), and biosensors for its
      tunable fluorescence, photothermal conversion property, and excellent
      biocompatibility. Surface passivation and doping especially the doping of N atoms
      are critical factors to enhance the fluorescent intensity of CDs. Until now, a
      variety of nitrogen-rich molecules has been applied for the surface passivation
      of CDs such as L-Dopa, amino acids, and polyethylenimine (PEI). Herein, we report
      the synthesis of fluorescent polydopamine (PDA)-passivated carbon dots (CD-PDA)
      via one-pot microwave-assisted pyrolysis within 5 min, dramatically simplifying
      the reaction process compared with the hydrothermal treatment reported before.
      DLS, FT-IR, UV-Vis, and fluorescence spectroscopy were used to confirm the
      components of CD-PDA and to illuminate the mechanism of its tunable
      photoluminescence (PL). Due to the doping of N atoms by PDA, quantum yield (QY)
      of the CD-PDA was measured at 5%, which was nearly triple the original CDs
      without adding PDA. Yield of CD-PDA was about 1.5 times of the CDs on account of
      the enhancement of nucleation site for the carbon dot formation with the phenolic
      group provided by PDA. Meanwhile, photothermal conversion efficiency of the CD
      PDA was determined to be 35% because of the excellent NIR light-thermal
      conversion property of PDA. Overall, we provided an extremely efficient approach
      to fabricate the fluorescent N-doped CD-PDA with stable photothermal conversion
      efficiency and excellent biocompatibility. More importantly, the passivation of
      PDA enabled the CD-PDA synthesized in our research compatible for further
      modification through Michael addition or Schiff base reaction.

PMID- 30225653
TI  - Correction to: Psychometric performance of the Romanian version of the SarQoL(r),
      a health-related quality of life questionnaire for sarcopenia.
AB  - The name and surname of the authors have been inverted. The correct order would
      be like this: Andrea Ildiko Gasparik, Gabriela Mihai, Charlotte Beaudart, Olivier
      Bruyere, Raluca-Monica Pop, Jean-Yves Reginster, Ionela Maria Pascanu.

PMID- 30225654
TI  - The type of stoma matters-morbidity in patients with obstructing colorectal
      cancer.
AB  - PURPOSE: A loop colostomy may reduce the risk of severe intraabdominal
      complications in patients with obstructing colorectal cancer compared to an end
      colostomy. The aim of this study was to relate complications to the type of
      stoma, and a secondary aim was to evaluate whether the type of colostomy had an
      impact on time until oncological/surgical treatment. METHODS: All patients who
      underwent surgery and received a deviating colostomy due to obstructing
      colorectal cancer between January 2011 and December 2015 in five Swedish
      hospitals in Region Vastra Gotaland were included (n = 289). Patient charts were
      reviewed retrospectively. Patients alive in the end of 2016 were contacted and
      were sent a questionnaire including questions about stoma function and health
      related quality of life. RESULTS: Some 289 patients were included; 147 received
      an end colostomy and 140 a loop colostomy. Two patients were excluded from the
      analysis due to missing data. There was no difference in complications at 90 days
      between the two groups, 44% (end colostomy) and 54% (loop colostomy) (odds ratio:
      0.83 (95% CI: 0.49; 1.41). Time to start of treatment was similar in both groups.
      Patients with a loop colostomy had significantly higher stoma-related morbidity
      with retraction, prolapse, leakage and bandaging problems. No differences in
      quality of life were found. CONCLUSION: The hypothesis that a loop colostomy
      reduced complications could not be confirmed. An end colostomy should be the
      first choice in these patients particularly in patients who will have their
      colostomy for the remainder of their life to reduce stoma-related symptoms.

PMID- 30225656
TI  - Health-related quality of life in patients with alveolar echinococcosis: a cross
      sectional study.
AB  - PURPOSE: The Alveolar echinococcosis (AE) is a rare zoonosis caused by the
      parasite Echinococcus multilocularis. To date, nothing is known about the health
      related quality of life (HRQoL) in patients with AE. The aim of the study was to
      evaluate the HRQoL in patients with AE in comparison of the healthy population.
      METHODS: We used the 36-Item Short Form Health Survey (SF-36) questionnaire to
      evaluate the HRQoL. The SF-36 scales have a range of 0-100 (0 represents the
      worst and 100 the most favourable state of health). SAS Version 9.2 was used for
      the statistical analysis of AE-cases (n = 30) and the healthy control group (n =
      35). RESULTS: The analysis showed that the HRQoL in people with AE is reduced in
      comparison with the control population. The study group consisted of 15 (50.0%)
      men and 15 (50.0%) women; the control group of 16 (45.7%) men and 19 (54.3%)
      women. The mean age was 55.73 +/- 16.65 years, while that of the control group
      was 54.57 +/- 15.34 years. The physical quality of life in patients with AE
      (45.21 +/- 11.42) was not significantly less than that of the control group
      (50.54 +/- 10.52); p = 0.0568. Nevertheless, AE-patients show lower SF-36 scores
      for the physical quality of life. For the mental quality of life, patients with
      AE had a significantly lower score (45.46 +/- 10.57) than the control group
      (51.57 +/- 9.04); p = 0.0154. CONCLUSIONS: The HRQoL in people with AE is reduced
      in comparison with a control population. Assessment of the physical and mental
      quality of life in patients with AE may help to evaluate the patient outcome.

PMID- 30225655
TI  - Correction to: Minimum Quality Threshold in Pre-Clinical Sepsis Studies
      (MQTiPSS): an international expert consensus initiative for improvement of animal
      modeling in sepsis.
AB  - The original version of this article unfortunately contained mistakes.

PMID- 30225657
TI  - A novel Sudan Black B-based analogue revives lipofuscin as a biomarker for in
      vivo senescence.

PMID- 30225658
TI  - Assessment of nail unit structures by ultrasound in patients with psoriatic
      arthritis and their correlations with disease activity indices: a case-control
      study.
AB  - Ultrasound (USG) of nail was performed to assess, (1) morphological alterations
      of nail plates in psoriatic arthritis (PsA) patients, (2) differences of nail
      unit parameters [nail bed thickness (NBT), nail matrix thickness (NMT) and nail
      plate distance (NPD)] in PsA patients from healthy controls (3) correlation of
      nail unit parameters with PsA disease activity indices. Total of 895 fingernails
      (448 nails of 45 PsA patients and 447 of 45 controls) were evaluated by USG.
      Psoriasis Area and Severity Index (PASI), Disease Activity in Psoriatic Arthritis
      (DAPSA), and Nail Psoriasis Severity Index (NAPSI) were calculated in PsA
      patients. Nail unit parameters were compared between two study groups.
      Correlation study was done between nail unit parameters and disease activity
      indices. All PsA patients showed ultrasound evidence of nail plate changes
      (87.95% of the total fingernails and 75.34% of the clinically normal nails).
      Loosening of the ventral nail plate border was most common (51.79%). Mean NBT
      (PsA: 0.19 +/- 0.035 cm, control: 0.17 +/- 0.018 cm, p = 0.003) and mean NMT
      (PsA: 0.32 +/- 0.041 cm, control: 0.28 +/- 0.031 cm, p = < 0.0001) were
      significantly increased in the PsA patients. Moderately positive correlation was
      observed between NAPSI score and mean NMT (Spearman r = 0.411, 95% confidence
      interval: 0.125-0.634, p = 0.005). USG evidence of nail plate alterations was
      frequent among PsA patients, even in clinically normal nails. Increased mean nail
      bed and matrix thickness were noted in PsA patients. Mean NMT had a moderately
      positive correlation with NAPSI score.

PMID- 30225660
TI  - Preclinical studies of stress, extinction, and prefrontal cortex: intriguing
      leads and pressing questions.
AB  - BACKGROUND: Stress is associated with cognitive and emotional dysfunction, and
      increases risk for a variety of psychological disorders, including depression and
      posttraumatic stress disorder. Prefrontal cortex is critical for executive
      function and emotion regulation, is a target for stress hormones, and is
      implicated in many stress-influenced psychological disorders. Extinction of
      conditioned fear provides an excellent model system for examining how stress
      induced changes in corticolimbic structure and function are related to stress
      induced changes in neural function and behavior, as the neural circuitry
      underlying this behavior is well characterized. OBJECTIVES: This review examines
      how acute and chronic stress influences extinction and describes how stress
      alters the structure and function of the medial prefrontal cortex, a potential
      neural substrate for these effects. In addition, we identify important unanswered
      questions about how stress-induced change in prefrontal cortex may mediate
      extinction deficits and avenues for future research. KEY FINDINGS: A substantial
      body of work demonstrates deficits in extinction after either acute or chronic
      stress. A separate and substantial literature demonstrates stress-induced
      neuronal remodeling in medial prefrontal cortex, along with several key
      neurohormonal contributors to this remodeling, and there is substantial overlap
      in prefrontal mechanisms underlying extinction and the mechanisms implicated in
      stress-induced dysfunction of-and neuronal remodeling in-medial prefrontal
      cortex. However, data directly examining the contribution of changes in
      prefrontal structure and function to stress-induced extinction deficits is
      currently lacking. CONCLUSIONS: Understanding how stress influences extinction
      and its neural substrates as well as individual differences in this effect will
      elucidate potential avenues for novel interventions for stress-sensitive
      disorders characterized by deficits in extinction.

PMID- 30225659
TI  - Effect of cannabidiolic acid and ?9-tetrahydrocannabinol on carrageenan-induced
      hyperalgesia and edema in a rodent model of inflammatory pain.
AB  - RATIONALE: Cannabidiol (CBD), a non-intoxicating component of cannabis, or the
      psychoactive Delta9-tetrahydrocannabiol (THC), shows anti-hyperalgesia and anti
      inflammatory properties. OBJECTIVES: The present study evaluates the anti
      inflammatory and anti-hyperalgesia effects of CBD's potent acidic precursor,
      cannabidiolic acid (CBDA), in a rodent model of carrageenan-induced acute
      inflammation in the rat hind paw, when administered systemically
      (intraperitoneal, i.p.) or orally before and/or after carrageenan. In addition,
      we assess the effects of oral administration of THC or CBDA, their mechanism of
      action, and the efficacy of combined ineffective doses of THC and CBDA in this
      model. Finally, we compare the efficacy of CBD and CBDA. RESULTS: CBDA given i.p.
      60 min prior to carrageenan (but not 60 min after carrageenan) produced dose
      dependent anti-hyperalgesia and anti-inflammatory effects. In addition, THC or
      CBDA given by oral gavage 60 min prior to carrageenan produced anti-hyperalgesia
      effects, and THC reduced inflammation. The anti-hyperalgesia effects of THC were
      blocked by SR141716 (a cannabinoid 1 receptor antagonist), while CBDA's effects
      were blocked by AMG9810 (a transient receptor potential cation channel subfamily
      V member 1 antagonist). In comparison to CBDA, an equivalent low dose of CBD did
      not reduce hyperalgesia, suggesting that CBDA is more potent than CBD for this
      indication. Interestingly, when ineffective doses of CBDA or THC alone were
      combined, this combination produced an anti-hyperalgesia effect and reduced
      inflammation. CONCLUSION: CBDA or THC alone, as well as very low doses of
      combined CBDA and THC, has anti-inflammatory and anti-hyperalgesia effects in
      this animal model of acute inflammation.

PMID- 30225661
TI  - Adverse oncological outcome of surgical site infection after liver resection for
      colorectal liver metastases.
AB  - PURPOSES: Postoperative complications are associated with poor overall and cancer
      specific survival after resection of various types of cancer, including primary
      colorectal cancer. However, the oncological impact of surgical site infection
      (SSI) after liver resection for colorectal liver metastases (CLM) is unclear. The
      aim of this study was to investigate the oncological impact of SSI after liver
      resection for CLM. METHODS: We reviewed data from 367 consecutive patients
      treated by curative liver resection for CLM between 1994 and 2015. Patients who
      underwent simultaneous resection of colorectal cancer and synchronous liver
      metastases (n = 86) were excluded from the analysis. Short- and long-term
      outcomes were analyzed. RESULTS: SSI developed in 18 (6.4%) of the 281 patients
      in the analytic cohort (SSI group). The remaining 93.6% (n = 263) did not suffer
      this complication (no-SSI group). The operative duration was significantly longer
      in the SSI group than in the No-SSI group (p = 0.002). The overall survival rates
      5 years after liver resection for CLM were 33.3% in the SSI group vs. 50.7% in
      the No-SSI group (p = 0.043). Multivariate analysis indicated that a liver tumor
      size >= 5 cm, R1 resection, and SSI were independently associated with overall
      survival after liver resection. CONCLUSIONS: SSI after liver resection for CLM is
      associated with adverse oncological outcomes.

PMID- 30225662
TI  - Boon or Burden: The Effect of Implementing Evidence-Based Practices on Teachers'
      Emotional Exhaustion.
AB  - This study examined the association between (1) beginning-of-the-year emotional
      exhaustion and use of three evidence-based practices (EBP) for children with
      autism spectrum disorder; and (2) use of these EBP and end-of-year emotional
      exhaustion among 46 kindergarden to 2nd grade autism support teachers
      participating in a randomized trial. Emotional exhaustion was measured at the end
      and beginning of the school year using a subscale of the Maslach Burnout
      Inventory. Fidelity was measured using monthly observations, coded by research
      assistants trained to reliability. Correlations were used to examine unadjusted
      associations and ordinary least squares regression was used to examine
      associations adjusted for beginning-of-year burnout, years teaching, and average
      change in student cognitive functioning. Emotional exhaustion at the beginning of
      the year was not associated with EBP use. Greater fidelity to each EBP was
      associated with lower end-of-year emotional exhaustion (coefficients ranging from
      - .34 to - 1.13, all p's < .05). Results indicate that helping teachers implement
      EBP with greater fidelity may help reduce burnout, a substantial challenge in the
      field.

PMID- 30225663
TI  - 1H NMR spectroscopy in the presence of Mosher acid to rapidly determine the
      enantiomeric composition of amino acid benzyl esters, chirons susceptible to easy
      racemization.
AB  - Amino acid benzyl esters are very useful chiral synthons, whose enantiomeric
      purity needs to be carefully verified because of their susceptibility to easy
      racemization. Alternative to chiral HPLC, 1H NMR in the presence of a chiral
      solvating agent (CSA) can allow a more rapid and acceptably accurate
      determination of the enantiomeric composition, if explicit spectral non
      equivalence of one or more protons of the analyte enantiomers is found. Here, we
      have studied the enantiodiscrimination of 13 amino acid benzyl esters by 1H NMR
      in the presence of (R)-Mosher acid and in different solvents proving that, for 5
      of them (Ala, Pro, Glu, Met, Ser), efficient enantiodifferentiation can be
      achieved and <= 98% enatiomeric excesses accurately determined. Generally, as
      expectable, the best enantiodifferentiated proton was that on the amino acid
      stereogenic alpha-carbon, but also the spectral non-equivalence of methyl protons
      and of protons on the beta-carbon and on the benzylic carbon could be exploited
      to distinguish the two enantiomers and to quantify the minor one. Structural
      feature favoring the amino acid ester enantiodiscrimination by the CSA seems to
      be low sterical hindrance at the amino acid beta-carbon.

PMID- 30225664
TI  - Taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma
      cells through PTEN/Akt pathways in vitro.
AB  - Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck malignancy
      with a high incidence in southern China. Previous studies have confirmed that
      taurine shows an anti-cancer effect on a variety of human tumors by inhibiting
      cell proliferation and inducing apoptosis. However, the underlying molecular
      mechanism of its anti-cancer effect on NPC is not well understood. To clarify
      these anti-cancer mechanisms, we performed cell viability and colony formation
      assays. Apoptotic cells were quantified by flow cytometry. The expression levels
      of apoptosis-related proteins were evaluated by Western blot. The results showed
      that taurine markedly inhibited cell proliferation in NPC cells, but only
      slightly in an immortalized normal nasopharyngeal cell line. Taurine suppressed
      colony formation and induced apoptosis of NPC cell lines in a dose-dependent
      manner. Furthermore, taurine increased the active form of caspase-9/3 in a dose
      dependent manner. Taurine down-regulated the anti-apoptotic protein Bcl-xL and up
      regulated the pro-apoptotic protein Bax and GRP78, a major endoplasmic reticulum
      (ER) chaperone. These results suggest the involvement of mitochondrial and ER
      stress signaling in apoptosis. In addition, taurine increased the levels of PTEN
      (phosphatase and tensin homolog deleted on chromosome 10) and p53, and reduced
      phosphorylated Akt (protein kinase B). In conclusion, taurine may inhibit cell
      proliferation and induce apoptosis in NPC through PTEN activation with
      concomitant Akt inactivation.

PMID- 30225666
TI  - Memetic Search Optimization Along with Genetic Scale Recurrent Neural Network for
      Predictive Rate of Implant Treatment.
AB  - Implant treatment is one of the most important surgical processes in teeth which
      reduces the difficulties in teeth by providing the interface between bone and
      jaw. The established implant treatment used to support the denture, bridge and
      teeth crown. Even though it supports many dental related activities, the
      successive measure of implant treatment is fail to manage because it fully
      depends on the patient's personal activities and health condition of mouth
      tissues. So, the successive rate of implant treatment process is identified by
      applying the memetic search optimization along with Genetic scale recurrent
      neural network method. The introduced method analyzes the patient characteristics
      which helps to recognize the successive and failure rate of implant treatment
      process. The quality of the implant treatment of using simulation results in
      terms of sensitivity, specificity and accuracy metrics.

PMID- 30225667
TI  - Open versus closed reduction and K-wire fixation for displaced supracondylar
      fracture of the humerus in children.
AB  - Supracondylar fracture of the humerus is a common displaced type childhood
      fracture that is treated by two methods. To compare open and closed methods of
      reduction with 2 cross k-wire fixation, a retrospective comparative study of 66
      paediatric patients with type III supracondylar fracture of the humerus, who were
      treated in two different hospitals utilizing two different protocols, was
      conducted. Group 1 was treated with open reduction and 2 cross k-wire fixation,
      and group 2 received the closed reduction and k-wire fixation protocol.
      Functional and cosmetic assessments were conducted utilizing the Flynn et al.
      outcome criteria. The test population consisted of 25 female (37.9%) and 41 male
      (62.1%) patients. There were 43 fractures (65.2%) in the right elbow and 23
      fractures (34.8%) in the left. Group 2 (81.81%) stayed less than 4 days in the
      hospital, while 69.7% of group 1 stayed more than 5 days. Statistically, there
      were no significant differences (P > 0.05) between patients of both groups
      regarding the Flynn et al. criteria. Closed reduction technique was preferred
      because it required less hospitalization time and resulted in almost no visible
      surgical scars.

PMID- 30225665
TI  - Effect of prolonged inspiratory time on gas exchange during robot-assisted
      laparoscopic urologic surgery.
AB  - BACKGROUND: Gas exchange disturbance may develop during urologic robotic
      laparoscopic surgery with the patient in a steep Trendelenburg position. This
      study investigated whether prolonged inspiratory time could mitigate gas exchange
      disturbances including hypercapnia. METHODS: In this randomized cross-over trial,
      32 patients scheduled for robot-assisted urologic surgery were randomized to
      receive an inspiratory to expiratory time ratio (I:E) of 1:1 for the first hour
      of pneumoperitoneum followed by 1:2 for last period of surgery (group A, n = 17)
      or I:E of 1:2 followed by 1:1 (group B, n = 15). Arterial blood gas analysis,
      airway pressure and hemodynamic variables were assessed at four time points (T1:
      10 min after induction of general anesthesia, T2: 1 h after the initiation of
      pneumoperitoneum, T3: 1 h after T2 and T4: at skin closure). The carry over
      effect of initial I:E was also evaluated over the next hour through arterial
      blood gas analysis. RESULTS: There was a significant decrease in partial pressure
      of oxygen in arterial blood (PaO2) for both groups at T2 and T3 compared to T1
      but in group B the PaO2 at T4 was not decreased from the baseline. Partial
      pressure of carbon dioxide in arterial blood (PaCO2) increased with I:E of 1:2
      but did not significantly increase with I:E of 1:1; however, there were no
      differences in PaO2 and PaCO2 between the groups. CONCLUSION: Decreased
      oxygenation by pneumoperitoneum was improved and PaCO2 did not increase after 1 h
      of I:E of 1:1; however, the effect of equal ratio ventilation longer than 1 h
      remains to be determined. There was no carryover effect of the two different I:E
      ratios.

PMID- 30225668
TI  - A useful combination for the treatment of patellofemoral chondral lesions:
      realignment procedure plus mesenchymal stem cell-retrospective analysis and
      clinical results at 48 months of follow-up.
AB  - INTRODUCTION: Osteochondral lesions of the patellofemoral joint (OLPFJ) are
      defects of the cartilage surface and subchondral bone, which often require
      surgical treatment. Reparative treatments have shown some limitations in the long
      term follow-up. The one-step bone marrow-derived cells transplantation (BMDCT)
      achieved good to excellent results in the treatment of osteochondral lesions of
      the femoral condyles. The aim of this study was to report the 48-month clinical
      and radiological results among 28 patients with OLPFJ treated with the one-step
      BMDCT technique associated with the anteromedialization tibial tuberosity (AMTT).
      MATERIALS AND METHODS: Twenty-eight patients from 2010 to 2013 with OLPFJ
      underwent the BMDCT with the one-step technique associated with the AMTT.
      Clinical evaluation was performed at 6, 12, 18, 24, 36 and 48 months after
      surgery using the Kujala PF scale, the IKDC score and the Tegner activity scale.
      Eighteen lesions were located on patella and ten lesions on trochlea. RESULTS:
      The preoperative Kujala score improved from 68.2 +/- 4.7 to 87.2 +/- 1.2 at the
      mean final follow-up, while the IKDC subjective score improved from 55.1 +/- 6.2
      to 92.13 +/- 5.5. Tegner scale showed an increase from 1.7 +/- 1.3 preoperatively
      to 5.3 +/- 2.7 at the final follow-up. MRI analysis at 24-month follow-up showed
      an overall good filling of the lesions. DISCUSSION AND CONCLUSIONS: The one-step
      BMDCT associated with the AMTT permitted good clinical results durable over time
      with a high rate of patients' satisfaction. These results confirm the validity of
      the one-step technique also in patellofemoral joint.

PMID- 30225669
TI  - A retrospective analysis of the periprocedural management of oral anticoagulants
      in patients undergoing interventional radiology procedures.
AB  - Limited evidence is available to guide periprocedural management of oral
      anticoagulants in the setting of interventional radiology (IR) procedures. For
      direct oral anticoagulants, therapy interruption (TI) is based on medication half
      life and procedural bleeding risk. Periprocedural management of warfarin includes
      INR monitoring, and possible bridging with parenteral anticoagulants. It is
      unknown if these recommendations apply to IR procedures. To evaluate bleeding
      complications and thromboembolic events following periprocedural management of
      the factor Xa (FXa) inhibitors or warfarin in patients undergoing IR procedures.
      We performed a retrospective, observational study at NYU Langone Health (NYULH)
      of all adult patients who underwent an IR procedure from January 2015 to July
      2017 and were receiving apixaban, rivaroxaban, or warfarin. Patients who were
      pregnant or who had a mechanical heart valve were excluded. At NYULH, TI is not
      required for FXa inhibitors, and an INR < 3 is recommended for patients on
      warfarin undergoing low risk procedures. For moderate/high risk procedures, TI
      for 48 h or 72 h with reduced renal function, is recommended for FXa inhibitors,
      and an INR < 1.5 is recommended for patients on warfarin. We evaluated 350 IR
      procedures, with a total of 174 low bleeding risk and 176 moderate/high bleeding
      risk. The 30-day major bleeding rate was 0.9%, clinically relevant non-major
      bleeding rate was 3%, minor bleeding rate was 1% and thromboembolic event rate
      was 1%. The periprocedural oral anticoagulation management strategy at NYULH
      appears safe given the low 30-day incidence of bleeding and thromboembolic
      events.

PMID- 30225670
TI  - Hyperoxia toxicity in septic shock patients according to the Sepsis-3 criteria: a
      post hoc analysis of the HYPER2S trial.
AB  - BACKGROUND: Criteria for the Sepsis-3 definition of septic shock include
      vasopressor treatment to maintain a mean arterial pressure > 65 mmHg and a
      lactate concentration > 2 mmol/L. The impact of hyperoxia in patients with septic
      shock using these criteria is unknown. METHODS: A post hoc analysis was performed
      of the HYPER2S trial assessing hyperoxia versus normoxia in septic patients
      requiring vasopressor therapy, in whom a plasma lactate value was available at
      study inclusion. Mortality was compared between patients fulfilling the Sepsis-3
      septic shock criteria and patients requiring vasopressors for hypotension only
      (i.e., with lactate <= 2 mmol/L). RESULTS: Of the 434 patients enrolled, 397 had
      available data for lactate at inclusion. 230 had lactate > 2 mmol/L and 167 <= 2
      mmol/L. Among patients with lactate > 2 mmol/L, 108 and 122 were "hyperoxia"- and
      "normoxia"-treated, respectively. Patients with lactate > 2 mmol/L had
      significantly less COPD more cirrhosis and required surgery more frequently. They
      also had higher illness severity (SOFA 10.6 +/- 2.8 vs. 9.5 +/- 2.5, p = 0.0001),
      required more renal replacement therapy (RRT), and received vasopressor and
      mechanical ventilation for longer time. Mortality rate at day 28 was higher in
      the "hyperoxia"-treated patients with lactate > 2 mmol/L as compared to
      "normoxia"-treated patients (57.4% vs. 44.3%, p = 0.054), despite similar RRT
      requirements as well as vasopressor and mechanical ventilation-free days. A
      multivariate analysis showed an independent association between hyperoxia and
      mortality at day 28 and 90. In patients with lactate <= 2 mmol/L, hyperoxia had
      no effect on mortality nor on other outcomes. CONCLUSIONS: Our results suggest
      that hyperoxia may be associated with a higher mortality rate in patients with
      septic shock using the Sepsis-3 criteria, but not in patients with hypotension
      alone.

PMID- 30225671
TI  - Classification of fruit trichomes in cucumber and effects of plant hormones on
      type II fruit trichome development.
AB  - MAIN CONCLUSION: Cucumber fruit trichomes could be classified into eight types;
      all of them are multicellular with complex and different developmental processes
      as compared with unicellular trichomes in other plants. The fruit trichomes or
      fruit spines of cucumber, Cucumis sativus L., are highly specialized structures
      originating from epidermal cells with diverse morphology, which grow
      perpendicular to the fruit surface. To understand the underlying molecular
      mechanisms of fruit trichome development, in this study, we conducted
      morphological characterization and classification of cucumber fruit trichomes and
      their developmental processes. We examined the fruit trichomes among 200 cucumber
      varieties, which could be classified into eight morphologically distinct types (I
      VIII). Investigation of the organogenesis of the eight types of trichomes
      revealed two main developmental patterns. The development of glandular trichomes
      had multiple stages including initiation and expansion of the trichome precursor
      cell protuberating out of the epidermal surface, followed by periclinal
      bipartition to two cells (top and bottom) which later formed the head region and
      the stalk, respectively, through subsequent cell divisions. The non-glandular
      trichome development started with the expansion of the precursor cell
      perpendicularly to the epidermal plane followed by cell periclinal division to
      form a stalk comprising of some rectangle cells and a pointed apex cell. The base
      cell then started anticlinal bipartition to two cells, which then underwent many
      cell divisions to form a multicellular spherical structure. In addition,
      phytohormones as environmental cues were closely related to trichome development.
      We found that GA and BAP were capable of increasing trichome number per fruit
      with distinct effects under different concentrations.

PMID- 30225672
TI  - The interaction between AtMT2b and AtVDAC3 affects the mitochondrial membrane
      potential and reactive oxygen species generation under NaCl stress in
      Arabidopsis.
AB  - MAIN CONCLUSION: AtMT2b interacts with AtVDAC3 in mitochondria in Arabidopsis.
      The overexpression of the AtMT2b and AtVDAC3 T-DNA insertion mutant confers
      tolerance to NaCl stress in Arabidopsis. Both AtMT2b and AtVDAC3 are involved in
      the regulation of the mitochondrial membrane potential (MMP) and reactive oxygen
      species (ROS) under NaCl stress. Metallothioneins (MTs) are small, cysteine rich,
      metal-binding proteins that perform multiple functions, such as heavy metal
      detoxification and reactive oxygen species (ROS) scavenging. MTs have been
      reported to be involved in mitochondrial function in mammals. However, whether a
      direct relationship exists between MTs and mitochondrial proteins remains
      unclear. In the present study, we used yeast two-hybrid and bimolecular
      fluorescence complementation assays to demonstrate that AtMT2b, which is a type 2
      MT in Arabidopsis, interacts with the outer mitochondrial membrane voltage
      dependent anion channel AtVDAC3. AtMT2b bound AtVDAC3, leading to its co
      localization in mitochondria. AtMT2b transgenic seedlings exhibited increased
      tolerance to salt stress, and the atvdac3 mutant showed a similar phenotype. The
      mitochondrial membrane potential (MMP) was maintained, and ROS generation was
      reduced following AtMT2b overexpression and AtVDAC3 knockout under NaCl stress.
      Both AtMT2b and AtVDAC3 were shown to be involved in MMP regulation and ROS
      production under NaCl stress but showed opposite effects. We conclude that AtMT2b
      might negatively interact with AtVDAC3 in mitochondria, and both proteins are
      involved in the regulation of MMP and ROS under NaCl stress.

PMID- 30225673
TI  - Complete genome sequence of a novel sea otterpox virus.
AB  - Members of the Poxviridae family are large, double-stranded DNA viruses that
      replicate in the cytoplasm of their host cells. The subfamily Chordopoxvirinae
      contains viruses that infect a wide range of vertebrates including marine mammals
      within the Balaenidae, Delphinidae, Mustelidae, Odobenidae, Otariidae, Phocidae,
      and Phocoenidae families. Recently, a novel poxvirus was found in a northern sea
      otter pup (Enhydra lutris kenyoni) that stranded in Alaska in 2009. The
      phylogenetic relationships of marine mammal poxviruses are not well established
      because of the lack of complete genome sequences. The current study sequenced the
      entire sea otterpox virus Enhydra lutris kenyoni (SOPV-ELK) genome using an
      Illumina MiSeq sequencer. The SOPV-ELK genome is the smallest poxvirus genome
      known at 127,879 bp, is 68.7% A+T content, is predicted to encode 132 proteins,
      and has 2546 bp inverted terminal repeats at each end. Genetic and phylogenetic
      analyses based on the concatenated amino acid sequences of 7 chorodopoxvirus core
      genes revealed the SOPV-ELK is 52.5-74.1% divergent from other known
      chordopoxviruses and is most similar to pteropoxvirus from Australia (PTPV-Aus).
      SOPV-ELK represents a new chordopoxvirus species and may belong to a novel genus.
      SOPV-ELK encodes eight unique genes. While the function of six predicted genes
      remains unknown, two genes appear to function as novel immune-modulators. SOPV
      ELK-003 appears to encode a novel interleukin-18 binding protein (IL-18 BP),
      based on limited sequence and structural similarity to other poxviral IL-18 BPs.
      SOPV-ELK-035 appears to encode a novel tumor necrosis factor receptor-like (TNFR)
      protein that may be associated with the depression of the host's antiviral
      response. Additionally, SOPV-ELK-036 encodes a tumor necrosis factor-like
      apoptosis-inducing ligand (TRAIL) protein that has previously only been found in
      PTPV-Aus. The SOPV-ELK genome is the first mustelid poxvirus and only the second
      poxvirus from a marine mammal to be fully sequenced. Sequencing of the SOPV-ELK
      genome is an important step in unraveling the position of marine mammal
      poxviruses within the larger Poxviridae phylogenetic tree and provides the
      necessary sequence to develop molecular tools for future diagnostics and
      epidemiological studies.

PMID- 30225674
TI  - Bone mineral density in osteoporotic patients with pyogenic vertebral
      osteomyelitis: effect of early versus late treatment for osteoporosis.
AB  - : Patients with pyogenic vertebral osteomyelitis (PVO) are at greater risk of
      bone loss. However, treatment guidelines for bone loss have been lacking. Early
      bisphosphonate treatment within 6 weeks after PVO diagnosis was significantly
      associated with superior outcome in femoral BMD at 2-year follow-up, compared to
      that with late treatment. INTRODUCTION: Due to absence of concern and proper
      guidelines, management of bone loss or osteoporosis in PVO is often neglected or
      delayed. A retrospective cohort study was planned to investigate differences in
      bone mineral density (BMD) in PVO patients with osteoporosis according to the
      timing of osteoporosis treatment. METHODS: The PVO cohort consisted of 192
      patients with osteoporosis who visited our institution between January 2003 and
      March 2015 and received bisphosphonate treatment for osteoporosis. According to
      the interval between PVO diagnosis and initiation of bisphosphonate, the patients
      were divided into three groups: group A (within 6 weeks after PVO diagnosis),
      group B (between 6 weeks and 3 months after diagnosis), and group C (more than 3
      months after PVO diagnosis). RESULTS: The percent increase in total femoral BMD
      in group A was significantly larger than that in group B at 2-year follow-up (p =
      0.036). Similarly, the percent increase in trochanteric (p = 0.008) and total
      femoral (p = 0009) BMD in group A was significantly larger than that in group C
      at 2-year follow-up. Even after multivariate adjustment, total femoral BMD
      changes were significantly associated with the treatment group. Group B (odds
      ratio = 2.824, p = 0.013) and group C (odds ratio = 3.591, p = 0.001) were more
      significantly associated with total femoral BMD decreases at 2-year follow-up
      compared with group A. CONCLUSIONS: Early bisphosphonate treatment within 6 weeks
      after PVO diagnosis (group A) was significantly associated with superior outcome
      in femoral BMD at 2-year follow-up, compared to that with late treatment (groups
      B and C).

PMID- 30225676
TI  - Imaging and Endovascular Treatment of Bleeding Pelvic Fractures: Review Article.
AB  - Pelvic fractures are potentially life-threatening injuries with high mortality
      rates, mainly due to intractable pelvic arterial bleeding. However, concomitant
      injuries are frequent and may also be the cause of significant blood loss. As
      treatment varies depending on location and type of hemorrhage, timely imaging is
      of critical importance. Contrast-enhanced CT offers fast and detailed information
      on location and type of bleeding. Angiography with embolization for pelvic
      fracture hemorrhage, particularly when performed early, has shown high success
      rates as well as low complication rates and is currently accepted as the first
      method of bleeding control in pelvic fracture-related arterial hemorrhage. In the
      current review imaging workup, patient selection, technique, results and
      complications of pelvic embolization are described.

PMID- 30225675
TI  - SMART (SiMulAtion and ReconsTruction) PET: an efficient PET simulation
      reconstruction tool.
AB  - BACKGROUND: Positron-emission tomography (PET) simulators are frequently used for
      development and performance evaluation of segmentation methods or quantitative
      uptake metrics. To date, most PET simulation tools are based on Monte Carlo
      simulations, which are computationally demanding. Other analytical simulation
      tools lack the implementation of time of flight (TOF) or resolution modelling
      (RM). In this study, a fast and easy-to-use PET simulation-reconstruction
      package, SiMulAtion and ReconsTruction (SMART)-PET, is developed and validated,
      which includes both TOF and RM. SMART-PET, its documentation and instructions to
      calibrate the tool to a specific PET/CT system are available on Zenodo. SMART-PET
      allows the fast generation of 3D PET images. As input, it requires one image
      representing the activity distribution and one representing the corresponding CT
      image/attenuation map. It allows the user to adjust different parameters, such as
      reconstruction settings (TOF/RM), noise level or scan duration. Furthermore, a
      random spatial shift can be included, representing patient repositioning. To
      evaluate the tool, simulated images were compared with real scan data of the NEMA
      NU 2 image quality phantom. The scan was acquired as a 60-min list-mode scan and
      reconstructed with and without TOF and/or RM. For every reconstruction setting,
      ten statistically equivalent images, representing 30, 60, 120 and 300 s scan
      duration, were generated. Simulated and real-scan data were compared regarding
      coefficient of variation in the phantom background and activity recovery
      coefficients (RCs) of the spheres. Furthermore, standard deviation images of each
      of the ten statistically equivalent images were compared. RESULTS: SMART-PET
      produces images comparable to actual phantom data. The image characteristics of
      simulated and real PET images varied in similar ways as function of
      reconstruction protocols and noise levels. The change in image noise with
      variation of simulated TOF settings followed the theoretically expected
      behaviour. RC as function of sphere size agreed within 0.3-11% between simulated
      and actual phantom data. CONCLUSIONS: SMART-PET allows for rapid and easy
      simulation of PET data. The user can change various acquisition and
      reconstruction settings (including RM and TOF) and noise levels. The images
      obtained show similar image characteristics as those seen in actual phantom data.

PMID- 30225677
TI  - Immunostimulatory activity of low-molecular-weight hyaluronan on dendritic cells
      stimulated with Aggregatibacter actinomycetemcomitans or Porphyromonas
      gingivalis.
AB  - OBJECTIVES: Periodontitis is a chronic inflammatory disease characterized by
      tooth-supporting tissue destruction, which is elicited by the host's immune
      response triggered against periodonto-pathogen bacteria. During periodontal
      tissue destruction, extracellular matrix components are metabolized and
      fragmented. Some extracellular matrix component-derived fragments, such as low
      molecular-weight hyaluronan (LMW-HA), have potent immunogenic potential, playing
      a role as damage-associated molecular patterns (DAMPs) during activation of
      immune cells. Dendritic cells (DCs) play a central role in the host's immune
      response displayed during periodontitis; thus, this study aimed to analyze
      whether LMW-HA has an immunostimulatory activity on DCs when stimulated with
      periodonto-pathogen bacteria. MATERIALS AND METHODS: LMW-HA-treated and non
      treated DCs were stimulated with Aggregatibacter actinomycetemcomitans or
      Porphyromonas gingivalis and the mRNA expression for cytokines tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1beta (IL-1B), interleukin-6 (IL-6), and
      interleukin-23 (IL-23A) was quantified by RT-qPCR. In addition, transcription
      factors interferon regulatory factor 4 (IRF4), interferon regulatory factor 8
      (IRF8), neurogenic locus notch homolog protein 2 (NOTCH2), and basic leucine
      zipper ATF-like transcription factor 3 (BATF3), involved in DC activation, were
      analyzed. RESULTS: Higher expression levels of TNF-alpha, IL-1B, IL-6, and IL-23A
      were detected in LMW-HA-treated DCs after bacterial infection, as compared with
      non-treated DCs. When LMW-HA-treated DCs were infected with A.
      actinomycetemcomitans, higher levels of IRF4, NOTCH2, and BATF3 were detected
      compared with non-treated cells; whereas against P. gingivalis infection,
      increased levels of IRF4 and NOTCH2 were detected. CONCLUSION: LMW-HA plays an
      immunostimulatory role on the immune response triggered by DCs during infection
      with A. actinomycetemcomitans or P. gingivalis. CLINICAL RELEVANCE: Detection of
      extracellular matrix component-derived fragments produced during periodontal
      tissue destruction, such as LMW-HA, could explain at least partly unsuccessful
      periodontal treatment and the chronicity of the disease.

PMID- 30225678
TI  - A prospective multicenter evaluation of immediately functionalized tapered
      conical connection implants for single restorations in maxillary anterior and
      premolar sites: 3-year results.
AB  - OBJECTIVES: This multicenter prospective clinical trial investigated immediately
      provisionalized, anodized, conical connection, tapered implants with platform
      shifting in maxillary anterior and premolar sites. MATERIALS AND METHODS:
      Patients requiring single-tooth implant-supported restorations in maxillary
      anterior and premolar sites were enrolled. Implants were immediately
      provisionalized and evaluated at insertion, 6 months, and annually thereafter.
      Outcome measures were marginal bone level change (DeltaMBL), cumulative survival
      rate (CSR), and success rate, soft-tissue parameters, and oral health impact
      profile (OHIP). DeltaMBL and Pink Esthetic Score were analyzed using Wilcoxon
      signed-rank tests. CSR was calculated using life table analysis. Other soft
      tissue parameters were analyzed using sign tests. RESULTS: Of 94 enrolled
      patients (99 implants), 84 (88 implants) attended the 3-year follow-up. After an
      initial bone loss between implant insertion and 6 months (- 0.92 +/- 1.23 mm),
      bone levels stabilized from 6 months to 3 years (0.13 +/- 0.94 mm) with no
      significant change. The 3-year CSR was 98.9%, and the cumulative success rate was
      96.9%. Papilla index scores of 2 or 3 were observed at 88.6% of sites at the 3
      year visit compared with 32.8% at implant insertion. Improvements were observed
      for all other outcomes, including bleeding on probing, esthetics, plaque, and
      OHIP. CONCLUSIONS: This restorative protocol was associated with high primary
      stability, patient satisfaction, stable bone levels, and an overall improvement
      of the soft tissue outcomes over a 3-year period. CLINICAL RELEVANCE: The
      presented treatment is a viable option for single-tooth restorations of maxillary
      anterior teeth and premolars with successful short- to mid-long-term clinical
      outcomes.

PMID- 30225679
TI  - Dentinal tubule penetration of AH Plus, BC Sealer and a novel tricalcium silicate
      sealer: a confocal laser scanning microscopy study.
AB  - OBJECTIVES: The aim of this in vitro study was to assess the dentinal tubule
      penetration of three different sealers, AH Plus, BC Sealer and a novel tricalcium
      silicate sealer (NTS). MATERIALS AND METHODS: Ninety-six human maxillary central
      incisors were divided into three experimental groups (n = 32) and were filled
      with gutta-percha using a single-cone technique in conjunction with one of the
      three sealers: AH Plus, BC Sealer or NTS. The roots in each group were cross
      sectioned at 1 and 5 mm from the root apex, and the surfaces were examined under
      confocal laser scanning microscopy (CLSM). The sealer penetration depths were
      measured at their maximum depths and at four circumferential depths (12, 3, 6 and
      9 o'clock) and were evaluated using ImageJ software (ImageJ, NIH). RESULTS: The
      maximum and mean penetration depths were significantly higher at 5 mm compared to
      1 mm from the apex in the AH Plus (p < 0.001), BC Sealer (p < 0.001) and NTS
      groups (p < 0.001). No significant difference was observed between the groups at
      1 mm for both parameters. The maximum and mean penetration depths were
      significantly lower at 5 mm for AH Plus compared with the other two groups (p =
      0.012). CONCLUSIONS: Within the study limitations, the BC Sealer and NTS
      demonstrated better tubule penetration results than the AH Plus sealer. CLINICAL
      RELEVANCE: Although no study has confirmed a relationship between the penetration
      depth of root canal sealers and the prevention of apical periodontitis, dentinal
      tubule sealer penetration may improve obturation quality.

PMID- 30225680
TI  - Oral exfoliative cytology and corrosion of metal piercings. Tissue implications.
AB  - OBJECTIVES: A group of adolescents with oral piercings was studied to determine
      the presence of metallic particles in cells exfoliated from the mucosa
      surrounding their metal oral piercings and the association between such particles
      and the metal jewelry, and to evaluate subsequent tissue implications. MATERIALS
      AND METHODS: Sixteen teenage patients who had tongue and/or lip piercings were
      included. The clinical features of the oral mucosa and lip skin were evaluated.
      Exfoliative cytology was performed in the area surrounding the piercing. The
      surface of used and unused jewelry was studied by scanning electron microscopy
      and energy dispersive X-ray analysis. RESULTS: Hyperplastic, leukoedematous, and
      lichenoid lesions were observed in the mucosa, as well as lesions associated with
      metallosis of the lip skin. Cytological smears showed the presence of particles
      inside the epithelial cells; the particles were found to contain aluminum,
      tungsten, and molybdenum. In one case requiring surgical removal of the piercing,
      histological examination of the tissue associated with the piece of jewelry
      showed the presence particles containing aluminum, iron, and tin inside
      multinucleated giant cells. Although surface finish defects were observed on both
      unused and used piercing jewelry, they were more evident on the used pieces.
      CONCLUSIONS: Ion particles are released from the metal piercings and could have
      been adjuvant factors in the development of the observed lesions. Cells
      exfoliated from the oral mucosa surrounding metal piercings may serve as
      bioindicators of corrosion processes. CLINICAL RELEVANCE: We propose the use of
      exfoliative cytology to monitor corrosion processes and for routine clinical
      follow up.

PMID- 30225681
TI  - Sensitivity limits of biosensors used for the detection of metals in drinking
      water.
AB  - Even when present in very low concentrations, certain metal ions can have
      significant health impacts depending on their concentration when present in
      drinking water. In an effort to detect and identify trace amounts of such metals,
      environmental monitoring has created a demand for new and improved methods that
      have ever-increasing sensitivities and selectivity. This paper reviews the
      sensitivities of over 100 recently published biosensors using various analytical
      techniques such as fluorescence, voltammetry, inductively coupled plasma
      techniques, spectrophotometry and visual colorimetric detection that display
      selectivity for copper, cadmium, lead, mercury and/or aluminium in aqueous
      solutions.

PMID- 30225682
TI  - Feasibility of biventricular volume and function assessment using first-pass
      gated 15O-water PET.
AB  - BACKGROUND: We investigated the feasibility of left ventricular (LV) and right
      ventricular (RV) volume and function estimation using a first-pass gated 15O
      water PET. This prospective study included 19 patients addressed for myocardial
      perfusion reserve assessment using 15O-water PET. PET data were acquired at rest
      and after regadenoson stress, and gated first-pass images were reconstructed over
      the time range corresponding to tracer first-pass through the cardiac cavities
      and post-processed using TomPool software; LV and RV were segmented using a semi
      automated 4D immersion algorithm. LV volumes were computed using a count-based
      model and a fixed threshold at 30% of the maximal activity. RV volumes were
      computed using a geometrical model and an adjustable threshold that was set so as
      to fit LV and RV stroke volumes. Ejection curves were fitted using a deformable
      reference curve model. LV results were compared to those obtained using 99mTc
      sestamibi gated myocardial SPECT in terms of end-diastolic volume (EDV), end
      systolic volume (ESV), stroke volume (SV), and ejection fraction (EF). RESULTS:
      There was an excellent concordance between rest and stress PET in terms of EDV
      and ESV (Lin's coefficient ~ 0.85-0.90), SV (~ 0.80), and EF (~ 0.75) for both
      ventricles. Correlation with myocardial SPECT was high for LV EDV (Pearson's R =
      0.89, p < 0.001) and ESV (R = 0.87, p < 0.001) and satisfying for LV SV (R =
      0.67, p < 0.001) and EF (R = 0.67, p < 0.001). Minimal LV ESV overestimation (+ 4
      mL, p = 0.03) and EF underestimation (- 4%, p = 0.01) were observed using PET.
      CONCLUSIONS: Biventricular volume and function assessment are achievable using
      the first-pass PET, and LV parameters correlate well with those derived from
      gated myocardial SPECT.

PMID- 30225684
TI  - Is an obstetrician/gynecologist a worker, artist, or scholar? Anxiety of an old
      professor.

PMID- 30225683
TI  - Chrysin attenuates interstitial fibrosis and improves cardiac function in a rat
      model of acute myocardial infarction.
AB  - Interstitial fibrosis after acute myocardial infarction (MI) leads to cardiac
      structural remodeling and dysfunction. The peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma) agonist chrysin has been shown to protect injured
      myocardium through suppression of oxidative stress and inflammation. This study
      was designed to investigate the effect and mechanism of chrysin on myocardial
      fibrosis. A rat MI model was created by ligating the left coronary artery. The
      rats with MI were treated with chrysin (40 mg/kg/day) or 0.5%
      carboxymethylcellulose sodium by intragastric administration for 4 weeks after
      operation. The effect of chrysin on cardiac fibroblasts (CFs) were also assessed
      in vitro. Echocardiography showed that cardiac function was significantly
      improved after chrysin treatment. Chrysin reduced the levels of MDA and SOD and
      GSH-Px in myocardial tissue. Chrysin attenuated the interstitial and perivascular
      fibrosis and the expression of collagenlin the peri-infarcted zone and remarkably
      decreased the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Chrysin up
      regulated PPAR-gamma and inhibited the nuclear factor-kappa B (NF-kappaB) pathway
      by suppressing inhibitor kappa B kinase beta phosphorylation.
      Immunohistochemistry analysis and PCR detected downregulated expression of AP-1
      after chrysin treatment. Chrysin also markedly reduced the increased alpha-SMA,
      typeland type III collagen expression of CFs mediated by AngII in vitro. In
      conclusion, chrysin has an antifibrosis cardioprotective effect on the infarct
      peripheral zone after MI. The underlined mechanism may be the up-regulation of
      PPAR-gamma and inhibition of the NF-kappaB and AP1 pathway.

PMID- 30225685
TI  - A prospective cohort study on the prediction of the diagnosis-to-delivery time in
      preeclamptic pregnancies: should the sFlt-1/PlGF ratio be added to routine
      evaluations?
AB  - PURPOSE: To analyze the clinical and laboratory factors that potentially affect
      the diagnosis-to-delivery time in preeclamptic pregnancies. METHODS: In this
      cross-sectional study, we followed 24 early onset preeclampsia (E-PE) and 26 late
      onset preeclampsia (L-PE) cases. Maternal serum samples were obtained at the time
      of diagnosis and stored at - 80  degrees C until ELISA analysis for soluble fms
      like tyrosine kinase-1 (SFlt-1) and placental growth factor (PlGF) levels.
      RESULTS: The median follow-up duration was 68 (1-339) h in the E-PE group and 330
      (7-1344) h in the L-PE group. Maternal mean arterial pressure (MAP) at
      hospitalization was the strongest variable, and the sFlt-1/PlGF ratio added
      significantly to the Cox regression model. In the E-PE cases, the median sFlt
      1/PlGF ratio was significantly higher in the subgroup with a follow-up duration >
      48 h than in the subgroup of cases with a follow-up duration <= 48 h (5109 vs.
      2080; p = 0.038), and none of the seven cases with an sFlt-1/PlGF ratio >= 75th
      percentile delivered during the first 48 h. Neither the 24-h proteinuria nor the
      gestational age at diagnosis added to the predictive power of the MAP at
      hospitalization. CONCLUSION: Incorporation of the sFlt-1/PlGF ratio to the
      routine evaluation of preeclamptic pregnancies may help in the prediction of
      progression and management planning.

PMID- 30225686
TI  - Validation of a quantitative system for real-time measurement of postpartum blood
      loss.
AB  - PURPOSE: Reliable real-time estimation of blood loss is crucial for the prompt
      management of postpartum hemorrhage (PPH), which is one of the major obstetric
      complications worldwide. Our study aims at the validation of feasibility and
      precision of measured blood loss (MBL) with a quantitative real-time measurement
      system during (1) vaginal delivery and (2) cesarean section by comparison with a
      hemoglobin-based formula for blood loss as an objective control. This is the
      first study to include a reasonable number of patients in an everyday clinical
      setting. METHODS: 921 patients were prospectively enrolled into this study
      (vaginal delivery: n = 461, cesarean delivery: n = 460) at a tertiary care
      hospital in Switzerland. Blood loss was measured by quantitative fluid collection
      bags. "Calculated blood loss" (CBL) was determined by modified Brecher's formula
      based on the drop of hemoglobin after delivery. MBL based on our measurement
      system was compared to CBL by correlation analysis and stratified by the mode of
      delivery. RESULTS: During vaginal delivery, MBL as determined by our quantitative
      measurement system highly correlated with CBL (p < 0.001, r = 0.683). This was
      also true for patients with cesarean deliveries (p < 0.001, r = 0.402), however,
      in a less linear amount. In women with cesarean deliveries, objectively low blood
      loss tended to be rather overestimated, while objectively high blood loss was
      more likely underestimated. CONCLUSIONS: The technique of real-time measurement
      of postpartum blood loss after vaginal delivery as presented in this study is
      practicable, reliable and strongly correlated with the actual blood loss and,
      therefore, poses an actual improvement in the management of PPH.

PMID- 30225687
TI  - Is vaginal progesterone treatment associated with the development of gestational
      diabetes? A retrospective case-control study.
AB  - PURPOSE: To determine the incidence of gestational diabetes mellitus (GDM) in
      pregnant women who received vaginal progesterone due to short cervical length or
      to prevent recurrent preterm birth. METHODS: In this retrospective study, we
      included 190 women with singleton pregnancies at risk for preterm birth who
      received vaginal natural progesterone (200 mg daily between gestational weeks 16
      + 0 and 36 + 0) for a minimum of 4 weeks and delivered > 28 weeks. The control
      group consisted of 242 age- and body mass index (BMI)-matched patients without
      progesterone administration. Data were acquired from a database containing
      prospectively collected information. Patients with pre-existing diabetes, and
      conception after in vitro fertilisation procedure were excluded. RESULTS: The
      incidence of GDM did not differ significantly between the progesterone-treated
      and the control group (14.7% vs. 16.9%, respectively; p = 0.597). In a binary
      regression model, patients with higher pre-pregnancy BMI (OR 1.1; p = 0.006), and
      those with a family history of diabetes had a higher risk for GDM development (OR
      1.8; p = 0.040), whereas vaginal progesterone treatment had no significant
      influence (p = 0.580). CONCLUSION: The use of vaginal progesterone for the
      prevention of recurrent preterm delivery and in women with a short cervix does
      not seem to be associated with an increased risk of GDM.

PMID- 30225688
TI  - Accumulation, translocation, and assessment of heavy metals in the soil-rice
      systems near a mine-impacted region.
AB  - Paddy rice is considered as a main source for human exposure to heavy metal
      contamination due to its efficient accumulation of heavy metals especially when
      cultivated in contaminated fields. In the current study, rice grains, straws,
      roots, and rhizosphere paddy soils were collected from Changsha, a non-ferrous
      mine-impacted area in China. Heavy metals including Cr, Mn, Fe, Co, Ni, Cu, Zn,
      As, Cd, Ba, and Pb in the samples were determined using ICP-MS. The heavy metal
      concentrations were found in the ascending order of grain < straw < root < paddy
      soil except As and Cd. Rice root is a main organ to retain As and Cd through
      chelation and adsorption. The translocation behaviors of the heavy metals in the
      soil-rice system were investigated through bioaccumulation factor (BF) and
      translocation factor (TF). Similar variation tendencies to decrease BFp-r
      (translocation from paddy soil to root) and TFs-g (translocation from straw to
      grain) associated with TFr-s (translocation from root to straw) increasing were
      observed for most of the heavy metals due to heavy metal detoxification and
      stress tolerance in rice. The potential adverse effects caused by long-term
      exposure to heavy metals from rice consumption were evaluated via the target
      hazard quotient. The results indicated potential health risk to human from
      exposure to Mn, As, and Cd.

PMID- 30225689
TI  - The TiO2 (B) nano-belts with excellent performance prepared via alkaline stirring
      hydrothermal method and its application to remove 17alpha-ethynylestradiol.
AB  - In this work, TiO2 (B) nano-belts were synthesized by hydrothermal method under
      stirring, and static conditions and preparation conditions were optimized. The
      prepared materials were characterized by scanning electron microscopy (SEM), high
      resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD),
      photoluminescence spectroscopy (PL), and N2 adsorption/desorption measurement.
      The photocatalytic performance was evaluated by removing synthetic estrogen
      17alpha-ethynylestradiol (EE2), which is the most potent endocrine-disrupting
      chemical. The results show that the TiO2 nano-belt possesses pure metastable
      monoclinic TiO2 (B) and has uniform nano-belt shape with 80~120-nm diameters and
      62.904 m2 g-1 of specific surface area. Under the best optimal preparation
      conditions (0.5 g P25, 20 mL 10 mol L-1 NaOH, hydrothermal temperature 180 
      degrees C for 18 h under stirring, 400  degrees C calcination for 2 h), the TiO2
      (B) has better catalytic activity with 100.00% removal rate towards 3 mg L-1 EE2
      in 120 min. The removal rates of EE2 over catalyst which was prepared under
      static condition and P25 are 74.66% and 70.71%, respectively. The photocatalytic
      degradation rate constant of TiO2 (B) prepared under stirring condition (0.0379
      min-1) is 4.51 times and 8.42 times than those of TiO2 prepared under static
      condition (0.0084 min-1) and P25 (0.0045 min-1). The excellent photocatalytic
      activity is mainly ascribed to longer one-dimensional nano-belt structure and
      effective suppression of photo-produced electron-hole.

PMID- 30225690
TI  - Assessing temporal-spatial land use simulation effects with CLUE-S and Markov-CA
      models in Beijing.
AB  - In order to solve the problem of extensive land use in rural residential areas
      and promote the construction of a new socialist countryside and farmland
      protection, it is important to graspe the temporal and spatial evolution of rural
      settlements. In this study, with Beijing as an example, the efficiencies of CLUE
      S and Markov-CA models in simulating spatial temporal evolution of rural
      residential areas are analyzed. With 14 driving factors chosen, the land uses in
      Beijing in 2000 and 2005 are simulated and predicted using the two models. Grid
      size of 220 m * 220 m is used. The accuracies and Kappa coefficients of the
      simulation and prediction results are analyzed and the following conclusions are
      made. The core part of CLUE-S model is logistic regression, which grants it
      obvious advantage in capturing the trends of land use changes with more discrete
      distributions. Meanwhile, Markov-CA model takes neighborhood into consideration,
      making it relatively more advantageous in simulating and predicting changes of
      land uses with the character of nearest-neighbor diffusion. However, among
      various land uses, only urban land use has this character, the correct prediction
      rates of the CLUE-S model in 2000 and 2005 were 60.99% and 81.35%, respectively,
      while the accuracy of the Markov-CA model prediction was 51.33% and 73.68%, and
      it is the main reason that CLUE-S model returns better simulation and prediction
      results of rural residential areas for both 2000 and 2005 than Markov-CA model.

PMID- 30225691
TI  - Rice single cropping or ratooning agro-system: which one is more environment
      friendly?
AB  - Sustainable development of food production depends on damping the environmental
      impacts of agricultural production. The aim of this study was to investigate the
      environmental performance of rice production in single crop and ratooning (main
      rice + ratoon crop) agro-systems through life cycle assessment (LCA) methodology
      in Guilan province, Northern Iran, in 2015. The flooding irrigation regime was
      the dominant irrigation method for single cropping system and main crop rising in
      ratooning agro-system. The data were gathered through a face to face interview
      with 215 single crop and 115 ratoon breeder paddy farmers. The environmental
      risks were determined in six impact categories including global warming,
      terrestrial eutrophication, acidification, and depletion of fossil fuels,
      phosphate, and potash resources. The functional unit (FU) was set as 100 kg
      protein. Results indicated that the CO2, N2O, and CH4 emissions of the rice
      ratooning agro-system (661.44, 1.96, and 5.42 kg 100 kg-1 protein) were less than
      the corresponding values in the rice single cropping agro-system (1341.63, 2.88,
      and 9.20 kg 100 kg-1 protein, respectively). Among all the environmental impact
      categories, the terrestrial eutrophication had the widest negative environmental
      effect followed by depletion of phosphate resources in single cropping agro
      system with weighted indices of 0.51 and 0.41, respectively. Moreover, the
      terrestrial eutrophication had the largest negative environmental effect followed
      by acidification in rice ratooning agro-system with weighted indices of 0.48 and
      0.29, respectively. Overall, the results highlighted that the rice ratooning ago
      system is more environmentally beneficial than the single cropping system,
      particularly in terms of depletion of fossil fuels, global warming, and depletion
      of phosphate and potash resources categories. This priority may be improved
      through adopting proper management of agronomic practices for main and ratoon
      rice in ratooning agro-system. Graphical abstract ?.

PMID- 30225692
TI  - Analysis of soil risk characteristics by comprehensive assessment in an
      industrial area of China.
AB  - Soil pollution in industrial areas poses a major challenge for China's
      environmental protection. In this study, comprehensive assessment methodologies
      for soil risk in industrial areas were developed. The comprehensive assessment
      covered ecological and human health risks of soil pollution, as well as
      vulnerability of different types of risk receptors. Comprehensive ecological risk
      assessment integrated potential ecological risk assessment and landscape
      vulnerability assessment. Comprehensive social risk assessment specialized human
      health risk assessment by introducing spatial distribution of population. A
      typical industrial area in China was studied, and the quantitative and spatial
      assessments of the comprehensive soil risk were presented. The results showed
      that the spatial distribution of soil comprehensive ecological and social risks
      differed. High-risk areas of soil comprehensive ecological risk in the study area
      were mainly farmlands and nature reserves. Inhabited areas and industrial zones
      were less affected by comprehensive ecological risk of soil. By contrast, the
      spatial distribution of soil comprehensive social risk and human activities
      showed a clear trend of convergence. Vulnerability assessment of the risk
      receptors provided a suitable complement to the risk assessment of soil
      pollution.

PMID- 30225693
TI  - Exertional heat illness: knowledge and behavior among construction workers.
AB  - Construction workers are considered one of the most vulnerable health group
      workers. Exertional heat illness (EHI) is a well-recognized health hazard that
      causes significant sickness and death. The purpose of this study was to assess
      construction workers' environment and hydration status and to evaluate the effect
      of health education program on workers. An interventional study was conducted on
      89 construction workers in Port Said City. Assessments of workplace environment
      and workers' hydration status were done by using workplace evaluation checklist,
      wet-bulb globe temperature, urine specific gravity, and urine color chart. A pre
      post-test design was used in the evaluation of workers' knowledge and behavior
      regarding EHI. A health education program was conducted to improve workers'
      knowledge and behavior; then, evaluation was done after 1 month. The most
      reported symptoms of heat illness were sweating (100.0%), dizziness (98.0%), and
      muscle pain (82.0%). Most workers showed signs of minimal dehydration (78.7%).
      There was a significant improvement in workers' knowledge about EHI and
      behavioral action for prevention after health education. Construction workers are
      at high risk of exposure to EHI which raised the attention to provide educational
      programs which can guide workers to follow healthy behaviors and prevent EHI.

PMID- 30225695
TI  - Effects of Exposure of Animals to Oxygen Atmosphere at Low Pressure on Lipid
      Peroxidation and Antioxidant Defense.
AB  - Relatively short-term (2.5 or 5 h) exposure of Wistar rats to oxygen atmosphere
      at moderate pressure (1.10-1.15 atm) resulted in an increase in LPO level and
      reduction of antioxidant activity in the blood serum. An increase in
      malondialdehyde concentration 1 day after termination of the exposure was
      followed by a decrease in the inhibiting activity of free radical oxidation of
      liposomal phospholipids induced by Fe(II) ions (100 MUm). Malondialdehyde
      concentration increased by 1.29 times already after 2.5-h exposure and did not
      changed when the duration of the exposure to oxygen atmosphere was prolonged to 5
      h. These data confirm the necessity of using substances potentiating antioxidant
      defense of the body during exposure to normobaric oxygenation.

PMID- 30225694
TI  - Pro-inflammatory effects of extracted urban fine particulate matter on human
      bronchial epithelial cells BEAS-2B.
AB  - Atmospheric particulate matter (PM) constitutes the major part of urban air
      pollution and is a heterogeneous mixture of solid and liquid particles of
      different origin, size, and chemistry. Human exposure to PM in urban areas poses
      considerable and significant adverse effects on the respiratory system and human
      health in general. Major contributors to PM content are combustion-related
      sources such as diesel vehicles, household, and industrial heating. PM is
      composed of thousands of different high molecular weight organic compounds,
      including poly-aromatic hydrocarbons (PAHs). The aim of this study was to clarify
      the cytotoxic effects of the extract of actual urban PM1 with high benzo[a]pyrene
      (BaP) content collected in Eastern European mid-sized city during winter heating
      season on human bronchial epithelial cells (BEAS-2B). Decreased cell viability,
      alteration of cell layer integrity, increased apoptosis, and oxidative stress
      were observed during the 3-day exposure to the PM extract. In addition, following
      PM exposure pro-inflammatory cytokine expression was upregulated at gene and
      protein levels. Morphology and motility changes, i.e., decreased cells' ability
      to cover scratch area, were also documented. We report here that the extract of
      urban PM1 may induce bronchial epithelium changes and render it pro-inflammatory
      and compromised within 3 days.

PMID- 30225696
TI  - Role of beta Cell Precursors in the Regeneration of Insulin-Producing Pancreatic
      beta Cells under the Influence of Glucagon-Like Peptide 1.
AB  - The effects of the pegylated form of glucagon-like peptide 1 (pegGLP-1) on
      oligopotent beta cell precursors (CD45-TER119-CD133+CD49flow) in the pancreas
      were studied in C57Bl/6 mice. Under conditions of streptozotocin-induced type 1
      diabetes mellitus, intraperitoneal injection of pegGLP1 increased the content of
      beta cell precursors and dithizone-stained cells in the pancreas. beta Cell
      precursors of mice with diabetes demonstrated high self-maintenance potential. In
      contrast to pegGLP-1, native GLP-1 did not affect beta cell precursors in
      diabetic animals. Treatment of a culture of beta cell precursors from mice with
      diabetes induced the yield of dithizone-stained mononuclears. In conditioned
      mediums of dithizone-positive cells obtained as a result of differentiation of
      beta cell precursors from mice with diabetes, insulin was detected after
      administration of pegGLP-1 (10-7 M) and glucose (3 mmol/liter); the level of
      insulin increased with increasing glucose concentration (to 20 mmol/liter). The
      in vitro effect of pegGLP-1 did not differ from the effect of GLP-1 (10-7 M).

PMID- 30225697
TI  - Antidiabetic Activity of Afobazole in Wistar Rats.
AB  - Using the streptozotocin model of type 2 diabetes mellitus in Wistar rats, we
      compared antidiabetic activity of anxiolytic Afobazole with that of metformin.
      Afobazole in a dose of 10 mg/kg reduced streptozotocin-induced hyperglycemia and
      polyphagia and prevented accumulation of malonic dialdehyde, being not inferior
      to metformin in a dose of 300 mg/kg, and was even more effective than metformin
      in body weight recovery, elimination of polydipsia, and preservation of these
      effects after treatment withdrawal.

PMID- 30225698
TI  - Specific Features of Depolarization of the Left and Right Atria in Rats with
      Alcoholic Cardiomyopathy.
AB  - Using a translation model of alcoholic cardiomyopathy in rats we showed the
      presence of an additional abnormal excitation focus in the area of the pulmonary
      vein lacunae in the left atrium and enhanced heterogeneity of the atrium
      depolarization pattern. These changes can determine electric instability of the
      myocardium and induce malignant heart rhythm disturbances including, sudden
      cardiac death.

PMID- 30225699
TI  - On the Mechanism of the Cardioprotective Action of sigma1 Receptor Agonist
      Anxiolytic Fabomotizole Hydrochloride (Afobazole).
AB  - Original translational rat model of chronic heart failure provoked by
      experimental anterior transmural myocardium infarction was employed to examine
      the preventive action of anxiolytic Afobazole (15 mg/kg/day administered
      intraperitoneally during the first 15 days after coronary occlusion) on the
      development of the heart failure assessed in 3 months after infarction. Afobazole
      prevented the development of pathologic remodeling of the myocardium, maintained
      its inotropic function, and decreased the plasma level of brain natriuretic
      peptide known as a biochemical marker of chronic heart failure. In the
      myocardium, Afobazole down-regulated overexpression of the genes induced in
      chronic heart failure and assessed by corresponding RNA levels, which code
      angiotensin (AT1A-R), vasopressin (V1A-R), and glucocorticoid (GR) receptors as
      well as Epac2 protein. The revealed biochemical changes are consistent with the
      data on cardioprotective action of Afobazole.

PMID- 30225700
TI  - Role of JAK/STAT3 Signaling in Functional Stimulation of Mesenchymal Progenitor
      Cells with Alkaloid Songorine.
AB  - JAK/STAT signaling pathway was examined comparatively during realization of
      growth potential of mesenchymal progenitor cells stimulated with diterpene
      alkaloid songorine or fibroblast growth factor. The stimulating role of JAKs and
      STAT3 on the mitotic activity and differentiation of progenitor cells cultured
      with songorine was revealed. Under these conditions, the study demonstrated
      suppression of fibroblast colony formation against the background of reduced
      number of actively proliferating CFU-fibroblasts and a drop of differentiation
      index of progenitor cells induced by pan-JAKs and STAT3 inhibitors. The observed
      changes were in almost complete agreement with the character of functional
      reactions of the progenitor elements in response to blockade of JAKs and STAT3
      with fibroblast growth factor. In addition, blockade of JAKs with this factor
      enhanced the differentiation rate of the progenitor cells.

PMID- 30225701
TI  - Peculiar Effects of Electromagnetic Millimeter Waves on Tumor Development in
      BALB/c Mice.
AB  - The study examined the effects of millimeter electromagnetic waves at a frequency
      of 130 GHz corresponding to the molecular absorption and radiation spectra of NO
      and O2 with the total exposition time of 6 h on tumor morphogenesis in 3- and 6
      month-old tumor-prone BALB/c mice of both sexes. In experimental mice exposed to
      electromagnetic radiation, the development of cancer process was slowed down
      throughout the observation period; moreover, no macroscopic signs of the tumors
      were revealed. However, in contrast to control mice, experimental animals
      demonstrated the formation of pathological reactions reflected by hepatic
      biochemical indices accompanied by the development of dystrophic and
      microcirculatory alterations in the liver tissue.

PMID- 30225702
TI  - Analysis of the Association of TNF -238G>A Gene Polymorphism with the Risk of
      Rheumatoid Arthritis Development in Russian Population in the Republic of
      Karelia.
AB  - We studied association of the TNF gene -238G>A polymorphism (rs361525) with the
      risk of rheumatoid arthritis development in the Russian population living in the
      Republic of Karelia. The influence of rs361525 on the development of rheumatoid
      arthritis was revealed: genetic predisposition to this disease is associated with
      the presence of GG genotype. The effect of the genotype on the polymorphic locus
      of -238G>A on TNF mRNA content was revealed. Increased content of transcripts of
      this gene is associated with the presence of A allele.

PMID- 30225703
TI  - Glycolysis Inhibitors Monoiodoacetate and 2-Deoxyglucose as Antitumor Agents:
      Experimental Study on Lewis Lung Carcinoma Model.
AB  - Antitumor effects of glycolysis inhibitors monoiodoacetate and 2-deoxyglucose
      were studied on Lewis lung carcinoma model. Monoiodoacetate exhibited antitumor
      and antimetastatic activities, being not inferior of methotrexate (reference
      drug); however, the preparation also demonstrated high systemic toxicity. 2
      Deoxyglucose exhibited only antitumor effect, while its antimetastatic activity
      did not differ from the result in the group without treatment.

PMID- 30225704
TI  - Changes in the Structure and Cell Composition of Human Carinal Lymph Nodes during
      Aging.
AB  - Changes in the structure and cell composition of carinal lymph nodes were studied
      in humans during aging. Replacement of node parenchyma with fibrous connective
      tissue progressing with age was demonstrated. The medullary matter significantly
      prevailed over the cortical substance. The lymph nodes in the cortical substance
      were small and had no light centers; the concentration of mature CD20+ B cells
      was high; the paracortical area was fragmented and thinned and contained no CD4+
      T helpers. Ki-67+ cells were absent in all structural components of the lymph
      nodes reflecting exhaustion of lymphopoietic function, which was determined by
      the replacement of the reticular tissue of the microenvironment with the
      connective tissue and by the absence of CD4+ T cells regulating cellular and
      humoral immunity. The disintegration of the reticular stroma in the sinus system
      that acts as a biological filter impairs the function of lymph purification.

PMID- 30225705
TI  - Blood Serum Levels of Proinflammatory Cytokines (IL-1beta, IL-6, TNFalpha, IL-8,
      IL-12p70, and IFNgamma) in Patients with Uterine Myoma.
AB  - We analyzed cytokine profile in blood serum of patients with uterine myoma and
      revealed significantly reduced level of IFNgamma and a tendency towards a
      decrease in the levels of IL-1beta and TNFalpha; the levels of IL-6, IL-8, and IL
      12p70 did not differ from those in healthy women. The drop in the concentrations
      of factors responsible for inflammation and angiogenesis in tissues are
      unfavorable for proliferation and differentiation of the uterine tissues.

PMID- 30225706
TI  - Mechanisms of Specific Embryonic Effects of Nitrogen Oxide.
AB  - The study of NO metabolism in chicken embryos showed that the intensity of
      oxidation of both endogenous and exogenous for the embryo NO donors to nitrate is
      determined by the presence or state of NO targets, rather than donor
      concentration. The mechanism of this oxidation and its physiological role are
      discussed. It was also shown that oxidation product nitrate is actively
      eliminated from the amnionic sac.

PMID- 30225707
TI  - Protective Effect of Dexamethasone on Lipopolysaccharide-Induced Inhibition of
      Contractile Function of Isolated Lymphatic Vessels and Nodes.
AB  - LPS has an inhibitory effect on contractile activity of bovine mesenteric
      lymphatic vessels and nodes and causes a pronounced decrease in the tone and
      phase contractions. The selective inhibitor of inducible NO synthase, 1400W, and
      cyclooxygenase-2 selective inhibitor, dynastat, significantly attenuated the
      inhibitory effect of LPS. Dexamethasone interferes with the inhibitory effect of
      LPS on bovine lymphatic vessels and nodes. It was concluded that LPS stimulates
      expression of inducible NO synthase and cyclooxygenase-2 in endothelial and
      smooth muscle cells of lymphatic vessels and nodes. Dexamethasone has a
      pronounced protective effect on the contractile function of lymphatic vessels and
      nodes affected by LPS and suppresses the expression of inducible NO synthase and
      cyclooxygenase-2.

PMID- 30225709
TI  - Effect of Neuropeptide Y on Action Potential Generation in Working Cardiomyocytes
      of the Right Atrium in Rat Heart.
AB  - We studied the effect of neuropeptide Y in concentrations of 10-8-10-6 M on
      electrical activity of adult rat right atrial cardiomyocytes with preserved
      spontaneous activity. Neuropeptide Y was found to modulate the amplitude-time
      parameters of action potential: in concentrations of 10-7 and 10-6 M it reduced
      the membrane potential, increased the amplitude of action potential and duration
      of the repolarization phase, and reduced the frequency of action potential
      generation. In concentration of 10-6 M, neuropeptide Y produced stronger effect
      on the analyzed parameters, while in concentration of 10-8 M it produced no
      significant changes.

PMID- 30225708
TI  - Epac Proteins and Calmodulin as Possible Arrhythmogenesis Trigger in Alcoholic
      Cardiomyopathy.
AB  - The expression of Epac proteins (exchange protein directly activated by cAMP) and
      calmodulin (CaM) was assessed by the content of the corresponding mRNA in biopsy
      specimens of cardiac atrium, left ventricle, and thoracic aorta of rats with
      alcoholic cardiomyopathy. In the myocardium, overexpression of Epac1, Eras2, and
      SaM mRNA was found. The content of Epac2 mRNA in the left ventricle was elevated
      by 2.9 times (p=0.000001), in the left atrium by 3.2 times (p=0.00001), in the
      right atrium by 3 times (p=0.00001). In contrast to the myocardial tissue, the
      content of CaM mRNA in the thoracic aorta was not increased, but showed a
      tendency to decrease, when compared to the control values, while the level of
      Epac1 and Epac2 mRNA was increased. The assumption is made that regulatory
      proteins Epac and CaM can play a key role in arrhythmogenesis development under
      conditions of alcoholic cardiomyopathy.

PMID- 30225710
TI  - Anti-Ischemic Activity of n-Tyrozol under Conditions of Repeated Transient
      Myocardial Ischemia in Rats.
AB  - We studied anti-ischemic activity of n-tyrozol under conditions of repeated
      transient myocardial ischemia in rats caused by repeated (5*3 min) occlusion of
      the left coronary artery. n-Tyrozol administered intraperitoneally in a dose of
      20 mg/kg daily over 4 days before the ischemia modeling (the last injection 15
      min prior to the start of the experiment) produced a clear-cut anti-ischemic
      effect: it reduced ST elevation and promoted more complete recovery of ECG during
      reperfusion. During reperfusion periods, n-tyrozol significantly decreased the
      risk of ventricular fibrillation and shortened the duration of tachyarrhythmia
      episodes (ventricular tachycardia and fibrillation).

PMID- 30225712
TI  - Wavelet Analysis of Electrocardiograms.
AB  - Some electrocardiograms, e.g. electrocardiograms recorded in patients with atrial
      fibrillation, myocardial infarction, or receiving some medications, contain waves
      of small amplitude. Despite low amplitude, these waves can significantly affect
      correct identification of the pathological process and diagnosis. The approach
      proposed by us allows studying these small waves using the wavelet analysis by
      constructing the corresponding wavelet image of ECG using special software. Two
      examples of construction of wavelet images of ECG in atrial fibrillation and
      myocardial infarction are presented.

PMID- 30225711
TI  - Development of Low-Molecular Weight Collagen Peptide Complex with
      Glycosaminoglycan Components.
AB  - Enzymatic hydrolysis of biopolymers of the cartilage tissue was studied for
      obtaining a complex of type II collagen peptides and glycosaminoglycan
      oligosaccharides. Hydrothermal hydrolysis in a high pressure homogenizer followed
      by enzymatic hydrolysis of the cartilage tissue biopolymers with proteolytic
      enzyme preparation Karipazim yielded a complex of collagen peptides and
      glycosaminoglycan oligosaccharides with molecular weights of 240-720 Da. Low
      molecular weight of the components increases their bioavailability. Entering into
      the cells (chondrocytes), low-molecular-weight peptides, disaccharides, and
      oligosaccharides as structural elements of the matrix can participate in the
      formation of fibrils of collagen and proteoglycans. Exogenous substances
      replenish deficient components of the matrix and/or their concentrations, affect
      the formation and strengthen the cartilage tissue. Thus, using cattle and porcine
      hyaline cartilages, we prepared a complex of biopolymers with lower molecular
      weights in comparison with previously developed nutraceuticals.

PMID- 30225713
TI  - Binding of Glyprolines to L-Arginine Inverts Its Analgesic and Antiagressogenic
      Effects.
AB  - We studied the effects of intraperitoneal administration of L-arginine in doses
      of 5, 15, and 50 MUg/kg and peptides in doses containing equimolar amount of this
      amino acid on aggressive-defensive behavior of rats (footshock model). The
      peptides were synthesized by binding of Pro-Gly-Pro sequence to one or both ends
      of the L-arginine molecule. The analgesic and antiagressogenic effects of L
      arginine and opposite effects of arginine-containing peptides (except Pro-Gly-Pro
      tripeptide) were demonstrated. The combination of arginine with glyprolines
      yielded peptides with intrinsic regulatory properties. This expands the
      possibilities of synthesis of drugs for correction of pain and aggression caused
      by pain.

PMID- 30225714
TI  - Effect of Atropine on Adrenergic Responsiveness of Erythrocyte and Heart Rhythm
      Variability in Outbred Rats with Stimulation of the Central Neurotransmitter
      Systems.
AB  - Single injection of muscarinic cholinoceptor blocker atropine (1 mg/kg) to
      outbred male rats reduced beta-adrenergic responsiveness of erythrocytes (by 2.2
      times) and the content of epinephrine granules on erythrocytes (by 1.5 times),
      significantly increased HR and rigidity of the heart rhythm, and manifold
      decreased the power of all spectral components of heart rhythm variability.
      Stimulation of the central neurotransmitter systems increased beta-adrenergic
      responsiveness of erythrocytes (by 15-26%), decreased the number of epinephrine
      granules on erythrocytes (by 25-40%), and increased HR and cardiac rhythm
      intensity. These changes were most pronounced after stimulation of the
      serotoninergic system. Administration of atropine against the background of
      activation of central neurotransmitter systems did not decrease beta-adrenergic
      responsiveness of erythrocytes (this parameter remained at a stably high level
      and even increased during stimulation of the dopaminergic system), but decreased
      the number of epinephrine granules on erythrocytes, increased HR, and
      dramatically decreased the power of all components of heart rhythm variability
      spectrum. The response to atropine was maximum against the background of
      noradrenergic system activation and less pronounced during stimulation of the
      serotoninergic system. Thus, substances that are complementary to cholinergic
      receptors modulated adrenergic effect on the properties of red blood cells,
      which, in turn, can modulate the adrenergic influences on the heart rhythm via
      the humoral channel of regulation. Stimulation of central neurotransmitter
      systems that potentiates the growth of visceral adrenergic responsiveness weakens
      the cholinergic modulation of the adrenergic influences, especially with respect
      to erythrocyte responsiveness. Hence, changes in the neurotransmitter metabolism
      in the body can lead to coupled modulation of reception and reactivity to
      adrenergic- and choline-like regulatory factors at the level of erythrocyte
      membranes, which can be important for regulation of heart rhythm.

PMID- 30225715
TI  - Effects of Semax on the Default Mode Network of the Brain.
AB  - The effects of nootropic drug Semax on the neuronal network of the brain were
      studied by the resting state functional magnetic-resonance imaging (resting state
      fMRI). The study was carried out on two groups of healthy volunteers (11 men and
      13 women aged 43.9+/-9.5 years). Resting state fMRI was carried out 3 times:
      directly before and 5 and 20 min after intranasal 1% Semax (14 subjects) or
      placebo (10 subjects). The topography of the resting state default mode network
      was studied. A greater volume of the default mode network rostral (medial frontal
      cortex) subcomponent was detected in the Semax group in comparison with controls.
      Resting state fMRI confirmed Semax effects on the neuronal network of the brain
      and demonstrated topography of these effects.

PMID- 30225716
TI  - Cardioprotective Activity of 2,6-Diisobornyl-4-Methylphenol in Acute Myocardial
      Ischemia/Reperfusion in Rats.
AB  - We studied the cardioprotective effect of 2,6-diisobornyl-4-methylphenol under
      conditions of myocardial ischemia/reperfusion in rats. Daily administration of
      2,6-diisobornyl-4-methylphenol (100 mg/kg intragastrically) over 3 days before
      and 5 days after modeling of myocardial ischemia/reperfusion prevented the
      increase in the infarction area by almost 2 times in comparison with the control
      by day 5 after recirculation. The type and severity of pathological changes in
      ECG parameters reflecting necrotic changes in the myocardium under the action of
      the compound significantly decreased by day 35 of the experiment. Animal survival
      rate during the first 24 h after ischemia/reperfusion modeling in the
      experimental group was by 29% higher than in the control group.

PMID- 30225717
TI  - Expression of microRNA Potentially Regulated by AhR and CAR in Malignant Tumors
      of the Endometrium.
AB  - We studied microRNA whose expression can be regulated by carcinogenic compounds.
      Bioinformatic analysis has detected microRNA potentially regulated by xenosensor
      receptors AhR (miR-28, miR-30c, miR-30e, miR-139, and miR-153) and CAR (miR-29c,
      miR-31, miR-185, miR-625, and miR-652). Published data indicate that these
      microRNAs are oncosuppressors, except miR-31 that can act as an oncogene. The
      expression of these microRNAs in malignant tumors of the endometrium was studied.
      The expression of the majority of the studied microRNAs, except miR-652, was 2-3
      fold below the normal, which confirms their oncosuppressor function and indicates
      their involvement in the endometrial carcinogenesis and hence, allows considering
      them as potential markers of the disease.

PMID- 30225718
TI  - Isoprenaline Impairs Contractile Function of Ventricular Myocardium in Common
      Frog (Rana temporaria).
AB  - The contractile function of the heart was studied in adult frogs Rana temporaria
      under the influence of a toxic dose of isoprenaline under conditions of natural
      sinoatrial rhythm and during heart pacing. The dynamics of ventricular pressure
      was recorded with a Prucka MacLab 2000 instrument via a catheter introduced into
      the ventricle through the ventricular wall. Reduced (p<0.05) parameters of the
      pump function (HR, maximum ventricular systolic pressure, isovolumic indices
      dP/dtmax and dP/dtmin) and lengthening of QRS complex and QT interval on ECG
      attested to impairment of contractile function and electrical processes after
      exposure to isoprenaline. Electrical stimulation of the right atrium improved
      myocardial contractility and ECG parameters after the administration of
      isoprenaline.

PMID- 30225719
TI  - Redox-Dependent Expression of Genes Encoding NADPH Oxidase 5 and the Key
      Antioxidant Enzymes during Formation of Drug Resistance of Tumor Cells to
      Cisplatin.
AB  - Expression of genes that plays a significant role in the control of cellular
      redox homeostasis was studied during the development of drug resistance of human
      ovarian adenocarcinoma SKOV-3 cells to cisplatin. It was found that the
      development of drug resistance was accompanied by enhanced expression of the
      genes encoding the key antioxidant enzymes (SOD2, CAT, GPX1, and HO-1) and
      transcription factor Nrf2, as well as reduced expression of the gene encoding
      NOX5 isoform of NADPH oxidase. The results testify to redox-dependent development
      of the adaptive antioxidant response as an important process in the mechanism of
      formation of resistance to cisplatin.

PMID- 30225720
TI  - Status of the Microcirculatory Network as a Factor of Prognosis and Evaluation of
      Therapeutic Efficiency in Prostate Cancer Treated by High-Intensity Focused
      Ultrasound in Combination with Androgen Deprivation.
AB  - Immunohistochemical and morphometric analysis of the microcirculatory bed in the
      tumor and non-tumor parenchyma of the prostate was carried out with the use of
      endothelial cell marker CD34 in patients treated by high-intensity focused
      ultrasound (HIFU). The numerical density of microvessels in the adenocarcinoma
      focus did not correlate with the degree of its differentiation, while high values
      of this parameter were associated with lower incidence of local progression after
      HIFU. Effective HIFU ablation led to progressive fibrosis and significant
      reduction of the microcirculatory bed in zones of intact non-tumor glands in
      control samples; an inverse relationship between the degree of reduction of the
      microcirculatory bed and the probability of relapse was revealed. The use of HIFU
      in combination with androgen deprivation was associated with a decrease in
      numerical density of microvessels in zones of tumor and non-tumor parenchyma in
      patients with relapses.

PMID- 30225722
TI  - Effective dose of remifentanil for intubation in children.

PMID- 30225721
TI  - Required cefazolin concentration to maximize diagnostic accuracy of the basophil
      activation test for cefazolin-induced anaphylaxis.
AB  - PURPOSE: Identifying the causative agent of perioperative anaphylaxis is key to
      preventing its recurrence. Besides skin testing, the basophil activation test
      (BAT) is increasingly being accepted as an additional and reliable method.
      Cefazolin seems to be a major cause of perioperative anaphylaxis. However, few
      studies have described use of the BAT for cefazolin-induced anaphylaxis. In this
      study, we aimed to determine the optimum cefazolin concentration required in the
      BAT for an accurate diagnosis. METHODS: Seven patients who presented with
      immediate hypersensitivity to cefazolin and 21 control subjects were studied. We
      conducted skin tests and performed BATs using both CD203c and CD63 as markers of
      activated basophils. We measured the ratio of activated basophils after
      stimulation with serial dilutions of cefazolin and investigated the cefazolin
      concentration that resulted in better sensitivity and specificity. RESULTS: All
      patients demonstrated positive reactions to cefazolin, while all control subjects
      showed negative reactions on skin tests. The net percentage of both CD203c- and
      CD63-labeled activated basophils was greater when higher concentrations of
      cefazolin than previously reported were used. In control subjects, however, the
      number of activated basophils by cefazolin stimulation was negligible regardless
      of its concentration. In the case of CD203c, the sensitivity was 86% with a
      cefazolin concentration of 3 mg/ml, while in the case of CD63, the sensitivity
      was 100% with a cefazolin concentration of 10 mg/ml. CONCLUSION: Using a higher
      concentration of cefazolin than previously reported for the BAT might increase
      the accuracy of diagnosis of cefazolin-induced anaphylaxis.

PMID- 30225723
TI  - Effects of resveratrol on regulation on UCP2 and cardiac function in diabetic
      rats.
AB  - Mitochondrial dysfunction is essential in the development and prognosis of
      diabetic cardiomyopathy (DCM). Resveratrol (RES) is thought as a mitochondrial
      protector. In this study, we hypothesized that RES may ameliorate mitochondrial
      function and consequently improve cardiac function in diabetic rats, and
      uncoupling protein 2 (UCP2) was involved in the protective effects of RES on DCM.
      Thirty rats were divided into three groups: normal control, DCM, and DCM+RES
      groups. DCM was induced by high-fat diet and streptozotocin (STZ) intraperitoneal
      injection, the rats in DCM+RES group received RES gavage for 16 weeks. RES
      improved the insulin resistance, and reduced the level of triglyceride,
      cholesterol, and low density lipoprotein cholesterol (LDLc) in DCM rats (all P <
      0.05). Echocardiographic and hemodynamic studies revealed that RES treatment
      reversed the impaired diastolic and systolic cardiac function in DCM rats.
      Meanwhile, RES improved myocardial structural disorder and fibrosis, reserved
      mitochondrial membrane potential level (P < 0.05), and suppressed myocardial
      apoptosis in DCM rats (P < 0.05). Myocardial mitochondrial respiratory enzyme
      activities were improved by RES treatment in DCM rats (P < 0.05), accompanied
      with attenuated reactive oxygen species (ROS) generation (P < 0.05). The
      expression of UCP2 was further increased by RES treatment both in the myocardium
      of DCM rats (P < 0.05) and in the H9c2 cardiomyocytes incubated with high-glucose
      (P < 0.05). The protective effects of RES on high glucose-induced ROS generation,
      MPTP opening, Cyto c release, and cell apoptosis were all blunted by inhibiting
      the expression of UCP2 (all P < 0.05). In conclusion, RES treatment improved
      cardiac function and inhibited cardiomyocyte apoptosis, involving in ameliorating
      mitochondrial function in diabetic rats. UCP2 mediated the protective effects of
      RES on diabetic hearts.

PMID- 30225724
TI  - SAMPL6 host-guest challenge: binding free energies via a multistep approach.
AB  - In this effort in the SAMPL6 host-guest binding challenge, a combination of
      molecular dynamics and quantum mechanical methods were used to blindly predict
      the host-guest binding free energies of a series of cucurbit[8]uril (CB8), octa
      acid (OA), and tetramethyl octa-acid (TEMOA) hosts bound to various guest
      molecules in aqueous solution. Poses for host-guest systems were generated via
      molecular dynamics (MD) simulations and clustering analyses. The binding free
      energies for the structures obtained via cluster analyses of MD trajectories were
      calculated using the MMPBSA method and density functional theory (DFT) with the
      inclusion of Grimme's dispersion correction, an implicit solvation model to model
      the aqueous solution, and the resolution-of-the-identity (RI) approximation
      (MMPBSA, RI-B3PW91-D3, and RI-B3PW91, respectively). Among these three methods
      tested, the results for OA and TEMOA systems showed MMPBSA and RI-B3PW91-D3
      methods can be used to qualitatively rank binding energies of small molecules
      with an overbinding by 7 and 37 kcal/mol respectively, and RI-B3PW91 gave the
      poorest quality results, indicating the importance of dispersion correction for
      the binding free energy calculations. Due to the complexity of the CB8 systems,
      all of the methods tested show poor correlation with the experimental results.
      Other quantum mechanical approaches used for the calculation of binding free
      energies included DFT without the RI approximation, utilizing truncated basis
      sets to reduce the computational cost (memory, disk space, CPU time), and a
      corrected dielectric constant to account for ionic strength within the implicit
      solvation model.

PMID- 30225725
TI  - Generalization after ocular onset in myasthenia gravis: a case series in Germany.
AB  - BACKGROUND AND PURPOSE: Approximately, 50% of myasthenia gravis (MG) patients
      initially present with purely ocular symptoms. Of these, about 60% will develop
      secondary generalized MG, typically within 2 years. Risk factors for secondary
      generalization are still controversial. In this study, we reviewed clinical
      parameters, thymic pathologies and medical treatments of MG patients with purely
      ocular symptoms at onset to investigate risk factors for secondary
      generalization. METHODS: In this monocentric retrospective study, we reviewed
      consecutive patients who underwent robotic thymectomy between January 2003 and
      October 2017 in Charite Universitaetsmedizin Berlin. We used univariate and
      multivariate Cox proportional hazards regression models to identify factors
      associated with secondary generalization. Survival curves were plotted using
      Kaplan-Meier method and log-rank tests were performed to analyze the association
      between corticosteroids use and secondary generalization in subgroups defined by
      anti-AChR antibody status and thymic pathology. RESULTS: One hundred and eighty
      of 572 MG patients who underwent robotic thymectomy were eligible for inclusion,
      of whom 110 (61.1%) developed a secondary generalized MG over a mean follow-up
      time of 23.6 months. The presence of a thymoma (HR 1.659, 95% CI (1.52-2.617), P
      = 0.029) was the only risk factor for secondary generalization in our series.
      Treating with corticosteroids was associated with a lower conversion rate in
      ocular myasthenia patients with thymic hyperplasia (n = 55, P = 0.028), but not
      with other thymic pathologies including thymoma and normal or atrophic thymus.
      CONCLUSIONS: The conversion rate in ocular myasthenia was high in our series,
      predicted by the presence of a thymoma. Our findings suggest that corticosteroids
      can prevent secondary generalization in ocular myasthenia patients with thymic
      hyperplasia, which requires further research.

PMID- 30225727
TI  - OFELIA: Prevalence of Osteoporosis in Fragility Fracture Patients.
AB  - Worldwide, a care gap has been recognized between presenting with a fracture and
      prevention of the next fracture. Fracture Liaison Service is the most cost
      effective method to close this gap, but its implementation is sparse in the
      Nordic countries. To assess the need for a fracture prevention program, the
      primary aim of this study was to estimate the prevalence of osteoporosis in
      patients treated for fragility fractures at Aarhus University Hospital, Denmark.
      Secondary aims were to identify clinical risk factors associated with
      osteoporosis and the up-take of anti-osteoporosis treatment. The study was
      conducted as a cross-sectional study and patients aged 18+ years were
      consecutively identified over a 12 months period. Of 1164 identified patients,
      832 were included and 794 (70% women, 66% aged >= 50 years) patients completed
      the study. Bone mineral density was measured by DXA and information about
      clinical risk factors were obtained. The overall prevalence of osteoporosis in
      this cohort was 14.9%, increasing to 20.3% in patients >= 50 years (22.9% in
      women, 9.6% in men). In addition to age above 50 years, female sex, low BMI, and
      early menopause were significantly associated with osteoporosis. At 3-years
      follow-up in patients diagnosed with osteoporosis, 95% of patients who initiated
      anti-osteoporosis treatment after their fracture were still adherent to
      treatment. Given that osteoporosis was demonstrated in one in five fragility
      fracture patients above 50 years, OFELIA stresses the need for implementation of
      a program aiming at securing appropriate investigation and treatment of
      osteoporosis in patients presenting a fragility fracture.

PMID- 30225726
TI  - Surgical strategy for an adult patient with a catecholamine-producing
      ganglioneuroblastoma and a cerebral aneurysm: a case report.
AB  - BACKGROUND: Ganglioneuroblastomas, particularly those that produce catecholamine,
      are extremely rare in adults. Here, we report an interesting surgical case of an
      adult patient with a catecholamine-producing ganglioneuroblastomas in her adrenal
      gland, suspected to be a pheochromocytoma, and with a cerebral aneurysm. CASE
      PRESENTATION: The patient was a 73-year-old woman under treatment for
      hypertension. During a health check-up, a cystic retroperitoneal tumor was
      incidentally found in the superior pole of her right kidney. Her blood adrenaline
      level was slightly elevated, and her urinary adrenaline, noradrenaline, and
      dopamine levels were above the upper reference limits. In addition, 24-h urinary
      excretion of metanephrine, normetanephrine, and vanillylmandelic acid were all
      increased. 123I-Meta-iodobenzylguanidine scintigraphy showed an abnormal
      accumulation of the marker in the cyst wall. She was, therefore, diagnosed with a
      pheochromocytoma and scheduled for tumor resection. However, preoperatively, 8-mm
      diameter cerebral aneurysm was incidentally found in her basilar artery. This
      required careful preoperative discussion. The aneurysm was difficult to approach
      and treat, and based on its position, shape, and size, the risk of rupture was
      low. Because hypertension is a major risk factor for aneurysmal rupture, we
      decided to proceed with the tumor resection. A lumbar catheter was placed to
      monitor the cerebral aneurysm for intraoperative rupture, and her transcranial
      motor-evoked potential and somatosensory-evoked potentials were monitored to
      track her intraoperative neurological function. During surgery, we carefully
      monitored fluctuations in blood pressure and resected the tumor with minimal
      mobilization. Postoperatively, head computed tomography confirmed that there was
      no sign of rupture. Histopathologically, the tumor was diagnosed as a
      catecholamine-producing ganglioneuroblastoma. The postoperative course was good,
      and the patient's blood pressure improved. CONCLUSIONS: Careful perioperative
      management is needed for a patient with both a catecholamine-producing tumor and
      cerebral aneurysm.

PMID- 30225728
TI  - Environmental impact assessment of uranium exploration and development on
      indigenous land in Labrador (Canada): a community-driven initiative.
AB  - There is hardly any study on environmental impacts of uranium exploration and
      mining development prior to actual mining activities. Rather, the majority of the
      literature addresses the environmental impacts of either ongoing or
      decommissioned mines. The objective of the study was to measure the possible
      radioactive contamination (total uranium and lead) in the local ecosystem
      surrounding an abandoned uranium development site on indigenous land in Labrador
      (Canada). Water (brook and ponds), soil/sediments (brook and ponds), plants
      (growing along the brook and pond shores), and local fish (trout) and clams from
      bays were collected from mine development site, downstream, and control sites.
      Uranium and lead mobilization in the local environment appears to be slightly
      enhanced near the proposed mining site, but rapidly drops downstream. Developing
      a low-cost, community-based environmental health monitoring tool is an ideal
      strategy for generating baseline information and further follow-up.

PMID- 30225729
TI  - Occurrence and fate of PPCPs in typical drinking water treatment plants in China.
AB  - In this study, the occurrence and removal of twenty-nine pharmaceuticals and
      personal care products (PPCPs) in two water treatment plants (WTPs) in China were
      investigated. WTP1 employed ozonation and granular active carbon (GAC) filtration
      after coagulation and sedimentation, while WTP2 applied anthracite and GAC
      filtration instead. In the influent, six and four selected PPCPs with total
      concentrations of 554.97 and 12.94 ng/L were detected in WTP1 and WTP2,
      respectively (in October), among which, sulfamethoxazole and erythromycin were
      detected with highest concentrations due to their widely used as both human and
      veterinary medicines. PPCPs removal varied significantly among compounds and
      treatment units. In general, coagulation, filtration and single GAC units worked
      inefficiently and removed the detected PPCPs by less than 50%, as they were not
      hydrophobic. Ozonation was capable to eliminate a majority of PPCPs by more than
      90%, which, however, presented limited mineralization and generated a certain
      amount of degradation by-products. To seek the improvement of PPCPs removal by
      coagulation and flocculation, the feasibility of adding hydrogen peroxide (H2O2)
      into the coagulation process (Fe2+ or Fe3+) to trigger the Fenton reaction was
      investigated. Results indicated that only under acidic condition, Fe2+ combined
      H2O2 efficiently removed PPCPs, while Fe3+/H2O2 also showed some removal capacity
      compared to coagulation process only. It will be impractical to employ this
      process under neutral pH. But when acidic wastewater is involved, this process
      may have its potential application.

PMID- 30225730
TI  - Analysis of groundwater variation in the Jinci Spring area, Shanxi Province
      (China), under the influence of human activity.
AB  - Jinci Spring is one of the most famous karst spring in Northern China and is the
      main drinking and irrigation water source of Taiyuan city, Shanxi Province. It
      has special significance in terms of humanities and water resources. Because of
      the continuous over-exploitation of groundwater, the water level of groundwater
      has been decreased significantly. The flow of Jinci Spring has decreased year by
      year since the 1970s, and in 1994 it cut off completely. The flow cutoff has
      brought huge losses to the local economy and negatively impacted the ecological
      environment. From the hydrogeological conditions of Jinci Spring area to study,
      the dynamic change in karst groundwater level will provide a basis for the
      protection and rational exploitation of karst water in the spring area. The
      previous research on Jinci Spring area was limited to the spring flow and water
      level changes, lack of analysis to the overall spring area and the decay process
      of spring flow. This paper takes the overall spring area as research object.
      According to groundwater level data over 1961-2012, the period is divided into
      two phases of decline and recovery. Human activities in the region and
      corresponding groundwater evolution at various stages were systematically
      analyzed, and the reservoir capacity was calculated for each period of decline.
      The results show that the average reservoir capacity decreased from 920 (1954
      1960) to 116 (1961-1977) to 31 (1978-1994) million m3. The important effect of
      "Water Resumption" project on groundwater in the area during the remediation
      period was also analyzed. In the light of observed increases in groundwater level
      during this stage, the project has a notably positive effect.

PMID- 30225731
TI  - Evaluation of the diagnostic ratios of adamantanes for identifying seriously
      weathered spilled oils from simulated experiment and actual oil spills.
AB  - The composition and physical properties of spilled oil have great changes during
      the seriously weathering process. It brings great difficulties to the source
      identification of oil spill. So the stable and trustworthy diagnostic ratios
      (DRs) for accurate identification of severely weathered spilled oils are very
      important. The explosion of Sinopec pipeline happened on November 22, 2013 at
      Qingdao, China. Local beaches at Jiaozhou Bay were polluted by spilled oils. We
      have collected original spilled oil samples from an area free from human
      interference near the oil leakage point after the accident. Synchronized with
      actual beach weathering, laboratory experiments were conducted to simulate oil
      weathering for 360 days by using the collected original spilled oil samples.
      Based on t test and the repeatability limit method, 50 diagnostic ratios (DRs) of
      adamantanes were screened. Four DRs, namely 1,3-dimethyladamantane/total
      dimethyladamantane, 1-methyladamantane/(1-methyladamantane + 1,3
      dimethyladamantane), dialkyl diamantane/total diamantane, and
      diamantane/(diamantane + dialkyl diamantane), have maintained remarkable
      stability during the simulated weathering experiments and field weathering
      process. These stable ratios can retain the characteristics of oil source during
      weathering. They are very beneficial to improve the accuracy of identifying the
      source of severely weathered oil and can be used as an effective supplement to
      existing index system for source identification.

PMID- 30225732
TI  - LILBID and nESI: Different Native Mass Spectrometry Techniques as Tools in
      Structural Biology.
AB  - Native mass spectrometry is applied for the investigation of proteins and protein
      complexes worldwide. The challenge in native mass spectrometry is maintaining the
      features of the proteins of interest, such as oligomeric state, bound ligands, or
      the conformation of the protein complex, during transfer from solution to gas
      phase. This is an essential prerequisite to allow conclusions about the solution
      state protein complex, based on the gas phase measurements. Therefore, soft
      ionization techniques are required. Widely used for the analysis of protein
      complexes are nanoelectro spray ionization (nESI) mass spectrometers. A newer
      ionization method is laser induced liquid bead ion desorption (LILBID), which is
      based on the release of protein complexes from solution phase via infrared (IR)
      laser desorption. We use both methods in our lab, depending on the requirements
      of the biological system we are interested in. Here we benchmark the performance
      of our LILBID mass spectrometer in comparison to a nESI instrument, regarding
      sample conditions, buffer and additive tolerances, dissociation mechanism and
      applicability towards soluble and membrane protein complexes. Graphical Abstract
      ?.

PMID- 30225734
TI  - Concomitant cardiac and cerebral takotsubo syndrome requires specific management.

PMID- 30225733
TI  - A pregnancy test strip for detection of pathogenic bacteria by using concanavalin
      A-human chorionic gonadotropin-Cu3(PO4)2 hybrid nanoflowers, magnetic separation,
      and smartphone readout.
AB  - Pregnancy test strips are widely used in daily life. A commercial pregnancy test
      strip was modified to obtain a point-of-care device for the detection of
      pathogenic bacteria. Hybrid nanoflowers were prepared from concanavalin A, human
      chorionic gonadotropin, and Cu3(PO4)2 via a one-pot method. They were used as
      signaling probes in an off-the-shelf pregnancy test strip. This modified lateral
      flow immunoassay can detect Escherichia coli O157:H7 with a detection limit of 4
      CFU.mL-1, and Salmonella typhimurium with a detection limit of 3 CFU.mL-1.
      Conceivably, the method has high potential as a portable and cost-effective tool
      for rapid determination of a wide range of analytes, especially in resource
      constrained settings. Graphical abstract Hybrid nanoflower loaded human chorionic
      gonadotropin (hCG) and concanavalin A (hCG - nanoflowers) were synthesized via a
      one-pot method and used as signal labels with commercial commercial-off-the-shelf
      pregnancy test strips to detect pathogenic bacteria targets, thus yielding an
      easily smartphone readout signal.

PMID- 30225735
TI  - Sustained onabotulinumtoxinA therapeutic benefits in patients with chronic
      migraine over 3 years of treatment.
AB  - BACKGROUND: Evidence on whether the therapeutic effect and good safety profile of
      onabotulinumtoxinA (Botox(r)) in chronic migraine (CM) patients is maintained
      over long term treatment is still limited. We herein aimed at assessing whether
      there is a sustained benefit and good safety with repeated onabotulinumtoxinA
      sessions in CM over more than three years of treatment. METHODS: We prospectively
      enrolled 65 CM patients, who were classified as responders after three sessions
      of onabotulinumtoxinA and were eligible to further continue treatment. Data
      documenting longitudinal changes from the trimester after the third
      onabotulinumtoxinA administration (T1) to the trimester after completing two
      years of treatment (T2) and eventually to the trimester after completing three
      years of treatment (T3) in (i) mean number of monthly headache days (ii) migraine
      severity as expressed by the mean number of days with peak headache intensity of
      > 4/10, and (iii) mean number of days with use of any acute headache medication,
      were prospectively collected from patients' headache diaries. RESULTS: A total of
      56 (86.1%) of 65 patients achieved to attain onabotulinumtoxinA over three years.
      At T3, a significant reduction in mean monthly headache days was evident,
      compared to T1 (3.4 +/- 1.7 vs 7.2 +/- 3.8; P < 0.001) with diminished mean
      number of monthly days with peak headache intensity of more than 4/10 and a
      significant change in days using acute headache medications per month between T1
      and T3 (2.8 +/- 1.3 vs 4.7 +/- 3.2; P < 0.001). Significant changes were also
      noticed in all efficacy variables from T2 to T3. Therapy was safe and well
      tolerated with low rates of adverse events or drop-outs. CONCLUSION: The long 
      term treatment with onabotulinumtoxinA proved effective, safe and well tolerated
      over three years. Our findings support the strategy to consistently deliver
      sessions of use of onabotulinumtoxinAlpha over long time in CM patients (Trial
      registration NTC03606356, registered retrospectively, 28 July 2018).

PMID- 30225737
TI  - Fluorescence Sensing Behavior for the Detection of Alcoholic Strength and Water
      Based on Two Novel Metallic Complex Edifices.
AB  - Alcoholic strength is a fundamental variable in industry production and its
      determination is crucial in technological developments. This study offers a novel
      strategy for fluorescent sensing of alcoholic content based on a terbium
      coordination complex. In pure water, the emissive compound displays blue
      luminescence. However, the addition of ethanol into the aqueous solution has
      induced the recovery of terbium green emissions. In another case, the achieved
      Eu(III)-phenanthroline complex shows high sensitivity to solvent polarity and the
      detection of trace amount of water can be realized through an "on-off" change
      with a low detection limit of 32.4 ppm.

PMID- 30225736
TI  - Wavelength-Selective Fluorescence of a Model Transmembrane Peptide: Constrained
      Dynamics of Interfacial Tryptophan Anchors.
AB  - WALPs are prototypical, alpha-helical transmembrane peptides that represent a
      consensus sequence for transmembrane segments of integral membrane proteins and
      serve as excellent models for exploring peptide-lipid interactions and
      hydrophobic mismatch in membranes. Importantly, the WALP peptides are in direct
      contact with the lipids. They consist of a central stretch of alternating
      hydrophobic alanine and leucine residues capped at both ends by tryptophans. In
      this work, we employ wavelength-selective fluorescence approaches to explore the
      intrinsic fluorescence of tryptophan residues in WALP23 in 1-palmitoyl-2-oleoyl
      sn-glycero-3-phosphocholine (POPC) membranes. Our results show that the four
      tryptophan residues in WALP23 exhibit an average red edge excitation shift (REES)
      of 6 nm, implying their localization at the membrane interface, characterized by
      a restricted microenvironment. This result is supported by fluorescence
      anisotropy and lifetime measurements as a function of wavelength displayed by
      WALP23 tryptophans in POPC membranes. These results provide a new approach based
      on intrinsic fluorescence of interfacial tryptophans to address protein-lipid
      interaction and hydrophobic mismatch.

PMID- 30225738
TI  - Single cell immunodetection of Escherichia coli O157:H7 on an indium-tin-oxide
      electrode by using an electrochemical label with an organic-inorganic
      nanostructure.
AB  - A rapid and highly sensitive method is described for the detection of
      enterohemorrhagic Escherichia coli O157:H7. An organic-inorganic nanostructure in
      which numerous gold nanoparticles (AuNPs) are enclosed with polyaniline (PANI)
      was utilized as an electrochemical label. The nanostructure showed (a) strong
      light scattering intensity due to the coupling effect of the surface plasmon
      resonance based on the presence of AuNPs, and (b) high electrochemical response
      due to the redox activity of PANI. To achieve selectivity, antibody against E.
      coli O157:H7 was immobilized on the surface of the nanostructure. The method
      exploits the combination of strong adsorption of bacterial cells onto the indium
      tin-oxide (ITO) glass electrode without any special processing and specific
      binding of the nanostructured label to E. coli O157:H7. This enables the
      electrochemical detection of a single cell on the ITO electrode. The
      electrochemical response to E. coli O157:H7 was 30-fold higher than that to other
      types of bacteria. This procedure can be applied to the determination of E. coli
      O157:H7 even in the presence of other bacteria. Graphical abstract Schematic of a
      voltammetric immunoassay for Escherichia coli O157:H7 by using a nanocomposite
      consisting of gold nanoparticles and polyaniline on an ITO electrode.

PMID- 30225739
TI  - Impact of reflux esophagitis on the esophageal function before and after
      laparoscopic fundoplication.
AB  - BACKGROUND: High-resolution manometry (HRM), which is breakthrough testing
      equipment to evaluate esophageal motor function, was developed in Europe and
      United State and has garnered attention. Moreover, multichannel intraluminal
      impedance pH (MII-pH) testing has allowed us to grasp all liquid/gas reflux
      including not only acid but also non-acid reflux. We examined the impact of the
      presence of reflux esophagitis (RE) on esophageal motor function before and after
      laparoscopic fundoplication. MATERIALS AND METHODS: The subjects included 100
      patients (male: 63 patients, mean age: 54.1 +/- 15.8) among 145 patients who
      underwent laparoscopic fundoplication for GERD associated diseases during a 4
      year period from October 2012 to September 2016, excluding 6 patients who
      underwent further surgery, 32 patients on whom HRM was not performed, 3 patients
      who had technical errors during testing, and 4 patients for whom the status of RE
      was unknown. Regarding HRM, Mano Scan from Given Imaging Ltd. was used, and for
      the analysis, Mano View version 3.0 from the same company was used, after which
      data was calculated based on the Chicago Classification advocated by Pandolfino
      et al. Moreover, for the MII-pH testing, Sleuth manufactured by Sandhill
      Scientific. Inc. was used and automatic analysis was conducted by a computer.
      Postoperative assessments were conducted 3 months following surgery for all. Data
      was described in the median value and inter-quartile range, with a statistically
      significant difference defined as p < 0.05 by Chi square, Mann-Whitney, and
      Wilcoxon tests. RESULTS: RE+ group (Los Angeles classification A:B:C:D =
      7:9:16:12 patients) included 44 patients (44%), of older age compared to the RE-
      group (62 vs. 50 years, p = 0.012) and a higher Body Mass Index value (24.0 vs.
      22.5, p = 0.045); however, no differences were observed in terms of gender and
      duration of symptoms. In the preoperative findings on MII-pH, the RE+ group
      demonstrated significantly longer acid reflux time (4.7 vs. 1.3%, p = 0.005),
      while in the HRM findings, the RE- group demonstrated a significantly longer
      abdominal esophagus (0 vs. 0.4 cm, p = 0.049) and maintained esophageal body
      motor function (DCI: 1054 vs. 1407 mmHg s cm, p = 0.021, Intact peristalsis
      ratio: 90 vs. 100%, p = 0.037). As to the comparison of the treatment effect
      before and after laparoscopic fundoplication (Toupet fundoplication for all),
      significant improvements were observed in both groups in various parameters
      regarding reflux including acid reflux time, total number of liquid reflux
      episodes and total number of reflux episodes. Moreover, for both groups, the
      total length of the lower esophageal sphincter (LES) (RE+ group: 2.7 vs. 3.2 cm,
      p = 0.001, RE- group: 3.0 vs. 3.4 cm, p = 0.003) and the total length of the
      abdominal esophagus (RE+ group: 0 vs. 1.6 cm, p < 0.001, RE- group: 0 vs. 1.8 cm,
      p = 0.001) were significantly extended following surgery; however, no change was
      observed in DCI before and after surgery. CONCLUSIONS: Regardless of the presence
      of RE, cardiac function and LES function were improved following laparoscopic
      Toupet fundoplication, but no changes were observed in esophageal body motor
      function.

PMID- 30225740
TI  - Hyponatremia in patients with esophageal cancer treated with chemotherapy
      including cisplatin.
AB  - BACKGROUND: Little is known about hyponatremia in patients with esophageal cancer
      treated with cisplatin-based chemotherapy. The aim of this study was to analyze
      the risk factors for hyponatremia and its effect on outcomes in patients with
      esophageal cancer treated with chemotherapy including cisplatin. METHODS: We
      retrospectively analyzed the records of 137 patients with esophageal cancer who
      received chemotherapy including cisplatin for the first time between January 2011
      and December 2014. RESULTS: Hyponatremia (Na < 135 mEq/L) was seen in 77 patients
      (59%), of whom 29 had Grade 3 (120 <= Na < 130 mEq/L) or Grade 4 (Na < 120 mEq/L)
      hyponatremia. We divided patients into the hyponatremia group (patients with Na <
      130 mEq/L) and the control group (patients with Na >= 130 mEq/L), and compared
      the results between the two groups. Three patients (2%) were diagnosed with the
      syndrome of inappropriate secretion of antidiuretic hormone. The serum sodium
      level before starting chemotherapy was significantly lower and white blood cell
      count was significantly higher in the hyponatremia group. Appetite loss was seen
      significantly more often in the hyponatremia group as the chemotherapy-related
      adverse effect. There was no significant difference in overall survival between
      the two groups. CONCLUSIONS: Hyponatremia is a common adverse effect induced by
      cisplatin. Caution should be exercised with patients with a low sodium level
      before starting chemotherapy. Hyponatremia can be associated with other
      chemotherapy-related adverse effects, and it should therefore be treated
      correctly.

PMID- 30225741
TI  - Surgical results of laparoscopic Toupet fundoplication for gastroesophageal
      reflux disease with special reference to recurrence.
AB  - BACKGROUND: Surgical results of GERD have mainly been reported from the Western
      countries, with a few reports found in Japan. We examined the surgical results of
      laparoscopic Toupet fundoplication and clarify the characteristics of recurrent
      cases. METHODS: The subjects included 375 patients who underwent laparoscopic
      Toupet fundoplication from June 1997 to December 2016 as the initial surgery.
      Patient characteristics, pathophysiology, and surgical results were examined. In
      addition, we compared the patient characteristics and pathophysiology of
      recurrent cases in comparison with non-recurrent cases. RESULTS: Age 59 (43-70)
      and male 211 (56.3%). The operation time was 141 min (113-180) and intraoperative
      complications were found to have onset in 13 subjects (3.5%). Dysphagia after
      surgery was found in 18 cases (4.8%). The A factor (the degree of hiatal hernia),
      P factor (the degree of esophagitis), and pH < 4 holding time significantly
      improved after surgery compared with prior to surgery (p < 0.001 for all), while
      the LES lengths and abdominal LES lengths were extended (p < 0.001 for each).
      Recurrence was found in 48 patients (15.1%) among the 318 patients for whom we
      could confirm the presence or absence of recurrence. The A factor, P factor, and
      pH < 4 holding time prior to surgery were, respectively, higher in the recurrence
      group (p = 0.031, p < 0.001, p < 0.001). CONCLUSIONS: Laparoscopic Toupet
      fundoplication for GERD could be performed safely, with a response rate as good
      as 85%. Compared with non-recurrent cases, preoperative clinical conditions such
      as esophageal hiatal hernia, reflux esophagitis, and acid reflux time were all
      advanced in recurrent cases.

PMID- 30225742
TI  - Involved-field chemoradiotherapy for postoperative solitary lymph node recurrence
      of esophageal cancer.
AB  - BACKGROUND: For patients with postoperative lymph node (LN) recurrent esophageal
      cancer, the appropriate irradiation field in chemoradiotherapy (CRT) remains
      controversial. We assessed the clinical outcomes and prognostic factors related
      to involved-field CRT for postoperative solitary LN recurrence of esophageal
      squamous cell carcinoma (ESCC). METHODS: We retrospectively evaluated 21 patients
      who had received curative resection, with LN recurrence of ESCC. Patients
      received CRT using 5-fluorouracil plus cisplatin or docetaxel, prescribed at 60
      Gy in 30 fractions. We evaluated the pattern of failure, toxicities, survivals,
      and prognostic factors. We defined elective nodal failure (ENF) as recurrence in
      a regional LN without involved-field failure. RESULTS: The median follow-up
      duration was 32 months (range, 4-106 months). Nine patients experienced failure-4
      (19%) within involved-field and 5 (24%) with distant metastasis. No patients had
      ENF. We observed no severe toxicities. The 2-year overall survival (OS) rate was
      78%. In the univariate analysis of OS, two factors, the maximal diameter of the
      metastatic LN < 25 mm and the absence of serum p53 antibodies (s-p53-Abs), were
      associated with a significantly better prognosis (p = 0.025 and p = 0.01,
      respectively). CONCLUSIONS: Involved-field CRT for postoperative solitary LN
      recurrence of ESCC did not cause ENF and was without severe toxicities. Two
      factors, a length of the metastatic LN < 25 mm and the absence of s-p53-Abs may
      improve the treatment outcome. Involved-field CRT is a treatment option worthy of
      consideration for postoperative solitary LN recurrence of ESCC.

PMID- 30225743
TI  - Lateral thermal spread and recurrent laryngeal nerve paralysis after minimally
      invasive esophagectomy in bipolar vessel sealing and ultrasonic energy devices: a
      comparative study.
AB  - BACKGROUND: This study aimed to compare the extent of lateral thermal spread of
      surrounding tissues after the use of advanced bipolar and ultrasonic coagulation
      and shearing devices. Association between recurrent laryngeal nerve paralysis
      (RLNP) and such devices was assessed in patients who underwent minimally invasive
      esophagectomy (MIE). METHODS: LigaSureTM (LS) and SonicisionTM (SONIC) were used.
      In ex vivo experiments using the porcine muscle, blade temperature and tissue
      temperature were measured using a thermometer after the activation of both
      devices. For the clinical assessment, 46 consecutive patients who received MIE
      were retrospectively assessed. RESULTS: The temperature generated at the blade of
      both devices increased with the activation time. The blade temperature of LS was
      significantly lower than that of SONIC (P < 0.001). The blade temperature of
      SONIC exceeded 100  degrees C after 3-s activation. The temperature of
      surrounding tissues after a single activation of the devices decreased with the
      tissue distance from activation blade. The temperatures of tissues at 1 and 2 mm
      away from the blade side of LS were significantly lower than those of SONIC (P =
      0.001 and P < 0.001, respectively). The temperature of tissue 2 mm away from the
      blade side of LS increased 6.4  degrees C from the baseline temperature.
      Furthermore, the incidence of RLNP in the LS group was lower than that in the
      SONIC group (P = 0.044). CONCLUSION: This study highlights the necessity of
      spatial and temporal recognition of the thermal spread of coagulation and
      shearing devices to reduce the thermal injuries following MIE.

PMID- 30225744
TI  - Association of level of anastomosis and anastomotic leak after esophagectomy in
      anterior mediastinal reconstruction.
AB  - AIM: The purpose of this study was to investigate modifiable predisposing factors
      associated with anastomotic leak in the anterior mediastinal (AM) reconstruction
      route. METHODS: We reviewed the data on 154 patients who underwent esophagectomy
      and gastric tube reconstruction using the AM route between 2008 and 2016. The
      data included computed tomography (CT) scans with sagittal reconstruction of the
      thoracic section. The level of the esophagogastric anastomosis (LEA) and
      pretracheal distance (PTD) was measured from sagittal reconstructed CT images.
      Vascularization of the gastric tube was evaluated by postoperative endoscopy.
      Variables associated with anastomotic leak were determined using univariate and
      multivariate analyses. RESULTS: Anastomotic leak developed in 13 patients (8%).
      The cut-off level at which the anastomosis was less likely to develop a leak, as
      determined by Chi-square tests, was 1.5 cm for LEA and 1.3 cm for PTD. On
      univariate analysis, the factors that were significantly associated with the risk
      of anastomotic leak included diabetes, hand-sewn anastomosis, the LEA >= 1.5 cm,
      and severe mucosal degeneration. On multivariate analysis, diabetes (OR 4.7, 95%
      CI 1.29-17.2), LEA >= 1.5 cm (OR 20.1, 95% CI 3.15-128), and severe mucosal
      degeneration (OR 7.2, 95% CI 1.42-36.8) were found to be statistically
      significant independent risk factors. CONCLUSION: Use of the AM route to place
      the cervical anastomosis within 1.5 cm above the suprasternal notch might avoid
      excessive pressure on the gastric tube from the surrounding structures, resulting
      in a reduction in the risk of an anastomotic leak.

PMID- 30225745
TI  - The effect of an elemental diet on oral mucositis of esophageal cancer patients
      treated with DCF chemotherapy: a multi-center prospective feasibility study (EPOC
      study).
AB  - PURPOSE: Oral mucositis (OM) is one of the most uncomfortable adverse events
      experienced by cancer patients undergoing chemotherapy. Previous reports have
      revealed that the oral administration of an elemental diet (ED) may prevent OM.
      However, the incidence of OM has not been accurately determined by specialized
      diagnostic methods and the effects of an ED on OM remain unclear. We investigated
      the dose that could feasibly be administered and its effects with regard to the
      suppression of OM in esophageal cancer patients undergoing chemotherapy. METHODS:
      We performed a prospective multi-center feasibility study of the administration
      of an ED (160 g/day) with 2 cycles of docetaxel/cisplatin/5-FU (DCF)
      chemotherapy. We assessed compliance to the ED for 49 days and the incidence of
      OM according to the amount of the ED that was orally administered. The incidence
      of OM was graded by a dental specialist who was experienced in dental oncology
      using a central OM review system. RESULTS: Fourteen of 20 patients (70%) were
      able to complete the orally administered ED (160 g/day) during the course of
      chemotherapy. Three patients (15%) could not take the ED orally for 9, 14, and 21
      days, respectively, while 1 patient (5%) took the ED orally at an average dose of
      80 g/day for 35 days. The remaining 2 patients (10%) could not take the 80 g/day
      dose for 11 and 12 days, respectively. The incidence of grade >= 2 OM in the ED
      completion group (15.4%, 2 of 13 patients) was significantly lower than that in
      the non-completion group (66.7%, 4 of 6 patients) (p = 0.046). CONCLUSIONS: An ED
      might be a one of the test treatment to reduce the incidence of OM in esophageal
      cancer patients treated with DCF and should be evaluated in further randomized
      study. CLINICAL TRIAL: The date of submission: Dec 08th, 2017.

PMID- 30225746
TI  - The effect of short-course gentamicin therapy on kidney function in patients with
      bacteraemia-a retrospective cohort study.
AB  - The nephrotoxic potential of aminoglycosides is primarily correlated to the
      duration of therapy. However, there are discrepancies between previous studies
      regarding the effect of short course treatment. The aim of this study was to
      compare renal function, renal recovery and mortality in a large cohort of
      patients with bacteraemia, who were empirically treated with regimens with and
      without a short course (<= 3 days) of once daily dosing of gentamicin. This was a
      retrospective propensity score-matched cohort study based on all patients with
      bacteraemia in a Danish hospital in the period 2010-2013. We included 702
      patients who received gentamicin, and 702 who did not receive gentamicin. To
      determine the impact of gentamicin on renal function, we used a modified version
      of the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for acute
      kidney injury (AKI), and the resulting data were analyzed by logistic regression.
      We used Cox regression analysis to compare the adjusted mortality rates between
      the two groups. According to the KDIGO criteria, we found no significant
      difference in the occurrence of AKI between the two groups (odds ratio (OR) 0.90
      (95% CI 0.68-1.20)). We found that recovery of renal function was similar in the
      two groups, OR 1.00 (95% CI 0.63-1.60). The hazard ratio for 90-day all-cause
      mortality was 1.02 (95% CI 0.84-1.25). Short-course empirical gentamicin
      treatment of patients with bacteraemia was not associated with an increased
      incidence of AKI nor all-cause mortality in this study, and we observed similar
      reversibility of renal function.

PMID- 30225748
TI  - Understanding the Role of ApoE Fragments in Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is one of the most devastating neurodegenerative
      diseases. It has been known for decades that the APOE E4 allele is the most
      significant genetic risk factor for late-onset AD and yet its precise role in the
      disease remains unclear. The APOE gene encodes apolipoprotein E (apoE), a 35 kDa
      glycoprotein highly expressed in the brain. There are three different isoforms:
      apoE3 is the most common allele in the population, whilst apoE2 decreases, and
      apoE4 increases AD risk. ApoE has numerous functions that affect neuronal and non
      neuronal cells, thus how it contributes to disease onset and progression is hotly
      debated. The apoE4 isoform has been linked to the accumulation of both of the
      major pathological hallmarks of AD, amyloid plaques containing amyloid beta
      peptides, and neurofibrillary tangles containing hyperphosphorylated tau protein,
      as well as other hallmarks of the disease, including inflammation and oxidative
      stress. Numerous studies have shown that apoE undergoes fragmentation in the
      human brain, and that the fragmentation pattern varies between isoforms. It was
      previously shown that apoE4 has neurotoxic functions, however recent data has
      also identified a neuroprotective role for the apoE N-terminal 25 kDa fragment,
      which is more prevalent in apoE3 individuals. The ability of the apoE 25 kDa
      fragment to promote neurite outgrowth was recently demonstrated and this suggests
      there is a potential loss of neuroprotection in apoE4 individuals in addition to
      the previously described gain of toxic function for specific apoE4 fragments.
      Here we review the enzymes proposed to be responsible for apoE fragmentation, the
      specific functions of different apoE fragments and their possible links with AD.

PMID- 30225749
TI  - The improved energy metabolism and blood oxygen-carrying capacity for pufferfish,
      Takifugu fasciatus, against acute hypoxia under the regulation of oxygen sensors.
AB  - Hypoxia frequently occurs in aquatic ecosystem, which is influenced by salinity,
      water temperature, weather, and surface water runoff. In order to shed further
      light on the evolutionary and adaptive mechanisms in fish under hypoxic
      condition, the impact of acute hypoxia (1.63 +/- 0.2 mg/L) and reoxygenation (7.0
      +/- 0.3 mg/L) on oxygen sensors, energy metabolism, and hematological indices was
      evaluated in Takifugu fasciatus. Data from transcriptional level analysis show
      that the expressions of genes related to oxygen sensors (HIF-1alpha, PHD2, and
      VHL) were upregulated in the brain and liver under hypoxia and recovered under
      reoxygenation. The upregulation of GLUT2, VEGF-A, and EPO in conjugation with
      VEGF-A protein and hematological indices conferred the rapid adjustments of
      cellular glucose uptake and blood oxygen-carrying capacities in pufferfish.
      Higher levels of glycolysis-related mRNAs (HK, PGK1, and PGAM2), HK activity, and
      proteins (PGK1 and PGAM2) were detected in the brain and liver under hypoxic
      condition compared with control. Interestingly, the expression of MDH1 at the
      mRNA, enzyme activity, and protein levels was significantly increased in the
      brain at 0 or 2 h and in the liver at 8 h under hypoxic condition. In addition,
      although the enzyme activity and mRNA expression of LDH in the brain were not
      significantly changed, a persistent upregulation was observed in the liver during
      hypoxia exposure. This study demonstrated that pufferfish could counterpoise the
      energetic demands and hematological functional properties evoked by oxygen
      sensors after hypoxia. Our findings provided new insights into the molecular
      regulatory mechanism of hypoxia in pufferfish.

PMID- 30225747
TI  - Intercistronic expression elements (IEE) from the chloroplast of Chlamydomonas
      reinhardtii can be used for the expression of foreign genes in synthetic operons.
AB  - KEY MESSAGE: Two intercistronic regions were identified as functional
      intercistronic expression elements (IEE) for the simultaneous expression of aphA
      6 and gfp in a synthetic operon in the chloroplast of C. reinhardtii.
      Chlamydomonas reinhardtii, a biflagellate photosynthetic microalga, has been
      widely used in basic and applied science. Already three decades ago,
      Chlamydomonas had its chloroplast genome transformed and to this day constitutes
      the only alga routinely used in transplastomic technology. Despite the fact that
      over a 100 foreign genes have been expressed from the chloroplast genome, little
      has been done to address the challenge of expressing multiple genes in the form
      of operons, a development that is needed and crucial to push forward metabolic
      engineering and synthetic biology in this organism. Here, we studied five
      intercistronic regions and investigated if they can be used as intercistronic
      expression elements (IEE) in synthetic operons to drive the expression of foreign
      genes in the chloroplast of C. reinhardtii. The intercistronic regions were those
      from the psbB-psbT, psbN-psbH, psaC-petL, petL-trnN and tscA-chlN chloroplast
      operons, and the foreign genes were the aminoglycoside 3'-phosphotransferase
      (aphA-6), which confers resistance to kanamycin, and the green fluorescent
      protein gene (gfp). While all the intercistronic regions yielded lines that were
      resistant to kanamycin, only two (obtained with intercistronic regions from psbN
      psbH and tscA-chlN) were identified as functional IEEs, yielding lines in which
      the second cistron (gfp) was translated and generated GFP. The IEEs we have
      identified could be useful for the stacking of genes for metabolic engineering or
      synthetic biology circuits in the chloroplast of C. reinhardtii.

PMID- 30225750
TI  - Glucose-6-phosphate dehydrogenase in blunt snout bream Megalobrama amblycephala:
      molecular characterization, tissue distribution, and the responsiveness to
      dietary carbohydrate levels.
AB  - This study aimed to characterize the full-length cDNA of glucose-6-phosphate
      dehydrogenase (G6PD) from Megalobrama amblycephala with its responses to dietary
      carbohydrate levels characterized. The cDNA obtained covered 2768 bp with an open
      reading frame of 1572 bp. Sequence alignment and phylogenetic analysis revealed a
      high degree of conservation (77-97%) among most fish and other higher
      vertebrates. The highest transcription of G6PD was observed in kidney followed by
      liver, whereas relatively low abundance was detected in eye. Then, the
      transcriptions and activities of G6PD as well as lipid contents were determined
      in the liver, muscle, and the adipose tissue of fish fed two dietary carbohydrate
      levels (30 and 42%) for 12 weeks. Hepatic transcriptions of fatty acid synthetase
      (FAS), acetyl-CoA carboxylase alpha (ACCalpha), sterol regulatory element-binding
      protein-1 (SREBP1), and peroxisome proliferator-activated receptor gamma
      (PPARgamma) were also measured to corroborate the lipogenesis derived from
      carbohydrates. The G6PD expressions and activities in both liver and the adipose
      tissue as well as the lipid contents in whole-body, liver, and the adipose tissue
      all increased significantly after high-carbohydrate feeding. Hepatic
      transcriptions of FAS, ACCalpha, SREBP1, and PPARgamma were also up-regulated
      remarkably by the intake of a high-carbohydrate diet. These results indicated
      that the G6PD of M. amblycephala shared a high similarity with that of other
      vertebrates. Its expressions and activities in tissues were both highly inducible
      by high-carbohydrate feeding, as also held true for the transcriptions of other
      enzymes and/or transcription factors involved in lipogenesis, evidencing an
      enhanced lipogenesis by high dietary carbohydrate levels.

PMID- 30225751
TI  - Molecular characterization and expression profiles of insulin-like growth factors
      in yellowtail kingfish (Seriola lalandi) during embryonic development.
AB  - In this study, to understand the role of the insulin-like growth factor (IGF)
      system in the regulation of early development in yellowtail kingfish (YTK,
      Seriola lalandi), an economically important marine fish species with a high
      potential for aquaculture, we first cloned the full-length cDNAs for igf1 and
      igf2 from the liver. YTK igf1 cDNA was 1946 base pairs (bp) in length with an
      open reading frame (ORF) of 558 bp encoding preproIGF1 of 185 amino acids (aa).
      The preproIGF1 consisted of 44 aa for the signal peptide, 68 aa for the mature
      peptide comprising B, C, A, and D domains, and 73 aa for the E domain. YTK igf2
      cDNA had an ORF of 648 bp that encoded a total of 215 aa spanning the signal
      peptide (47 aa), the mature peptide (70 aa), and the E domain (98 aa). At the
      protein level, both YTK IGF1 and IGF2 exhibited high sequence identities with
      their corresponding fish counterparts, respectively. Subsequently, quantitative
      RT-PCR analysis indicated that the highest level of igf1 mRNA expression was
      recorded in the gonad and liver, while the igf2 mRNA expression was most abundant
      in the gill and liver. In addition, both igf1 and igf2 were detected in all
      stages of embryonic development and exhibited different gene expression patterns,
      supporting that IGF1 and IGF2 could be functional and play important roles during
      YTK embryogenesis. Overall, this initial study of IGF1 and IGF2 provides an
      insight into the endocrine mechanism involved in the early development of
      yellowtail kingfish.

PMID- 30225752
TI  - Efficient immortalization of cells derived from critically endangered Tsushima
      leopard cat (Prionailurus bengalensis euptilurus) with expression of mutant CDK4,
      Cyclin D1, and telomerase reverse transcriptase.
AB  - Tsushima leopard cat is the subspecies of Amur cats, and it is classified as the
      most highest class of critically endangered animals. Although the protection
      activity is highly recognized, the number of animals is decreasing due to the
      human activity and invasion of domestic cats and infectious disease. In this
      study, we succeeded primary culture of normal fibroblasts derived from the
      Tsushima leopard cat (Prionailurus bengalensis euptilurus). Furthermore, we
      introduced the human derived mutant Cyclin Dependent Kinase 4, Cyclin D1, and
      telomere reverse transcriptase. We showed that the expression of these three
      genes efficiently immortalized cells derived from Tsushima leopard cat.
      Furthermore, we showed that the chromosome pattern of the established cells is
      identical with the original one. These data indicate that our method of
      immortalization is useful to establish cell lines from critically endangered
      cats, which potentially contributes to the re-generation of critically endangered
      animals from cultured cell with reproductive technique, such as somatic cloning.

PMID- 30225753
TI  - Slipknot small bowel obstruction.

PMID- 30225754
TI  - Preoperative surgical planning based on cadaver simulation and 3D imaging for a
      retrorectal tumour: description and video demonstration.

PMID- 30225755
TI  - Combined transanal minimally invasive surgery (TAMIS) and retroperitoneal
      laparoscopy for resection of lymph node recurrence of ovarian cancer.

PMID- 30225756
TI  - Concentration of Micro- and Macro-Elements in Green and Roasted Coffee: Influence
      of Roasting Degree and Risk Assessment for the Consumers.
AB  - The aim of the present study was to determine concentrations of 15 macro- and
      micro-elements in 10 commercially available plantation Arabica coffee brands. The
      elemental concentration was studied in 50 samples of green and roasted coffee
      beans of various roasting degrees and their infusions. There were four different
      roasting degrees: City + (C+), Full city (FC), Full city ++ (FC++), and Dark (D).
      The attention was given to the impact of the roasting process on the elemental
      composition. Statistically significant differences were found between the green
      coffee beans and the different roasting degrees in both macro- and micro
      elements. The results showed that roasting degrees affected the concentration of
      elements in resulting infusions. Dietary intakes for macro- and micro-elements
      based on RDA and PTWI (in the case of Al) were calculated. Based on the RDA
      values for macro- and micro-elements, it can be concluded that coffee infusions
      are not an important source of elements in nutrition. In the case of Al,
      consumption of coffee was considered non-hazardous based on the PTWI value.

PMID- 30225757
TI  - Carcinogenic and Non-carcinogenic Risk Assessment of Heavy Metals in Groundwater
      Wells in Neyshabur Plain, Iran.
AB  - The present work reports the As, Cr, Cu, Pb, Zn, and Fe concentrations of
      drinking water samples in Neyshabur Plain, Iran. This study aimed also to
      ascertain the potential consumers' health risk of heavy metal intake. Heavy metal
      concentrations were analyzed by inductively coupled plasma optical emission
      spectrometry. The highest and lowest average values in the analyzed water samples
      were observed for Fe (9.78 +/- 5.61 MUg/L) and As (1.30 +/- 2.99 MUg/L),
      respectively. These values were well below the limits recommended by the World
      Health Organization and the Iranian national standard. Heavy metal pollution
      index and heavy metal evaluation index were used to evaluate drinking water
      quality. The risk index was calculated by chronic daily intake and hazard
      quotient according to the United States Environmental Protection Agency approach.
      Heavy metal pollution index in all the samples was less than 100, indicating that
      it is a low-level heavy metal. The total risk of all heavy metals in the urban
      environment varied from 40.164 * 10-7 to 174.8 * 10-7. In this research, the
      maximum average of risk belonged to lead and copper with the respective values of
      60.10 * 10-7and 33.99 * 10-7 from the selected wells. However, considering the
      toxic effect of some elements, including Pb and As, in the chronic exposure of
      consumers, we suggest a continuous evaluation and monitoring of drinking water
      resources.

PMID- 30225758
TI  - Pharmacokinetic Modeling of Targeted Ultrasound Contrast Agents for Quantitative
      Assessment of Anti-Angiogenic Therapy: a Longitudinal Case-Control Study in Colon
      Cancer.
AB  - PURPOSE: To evaluate quantitative and semi-quantitative ultrasound molecular
      imaging (USMI) for antiangiogenic therapy monitoring in human colon cancer
      xenografts in mice. PROCEDURES: Colon cancer was established in 17 mice by
      injection of LS174T (Nr = 9) or CT26 (Nn = 8) cancer cells to simulate clinical
      responders and non-responders, respectively. Antiangiogenic treatment
      (bevacizumab; Nrt = Nnt = 5) or control treatment (saline; Nrc = 4, Nnc = 3) was
      administered at days 0, 3, and 7. Three-dimensional USMI was performed by
      injection at days 0, 1, 3, 7, and 10 of microbubbles targeted to the vascular
      endothelial growth factor receptor 2 (VEGFR2). Microbubble binding rate (kb),
      estimated by first-pass binding model fitting, and semi-quantitative parameters
      late enhancement (LE) and differential targeted enhancement (dTE) were compared
      at each day to evaluate their ability to assess and predict the response to
      therapy. Correlation analysis with the ex-vivo immunohistological quantification
      of VEGFR2 expression and the percentage blood vessel area was also performed.
      RESULTS: Significant changes in the USMI parameters during treatment were
      observed only in the responders treated with bevacizumab (p-value < 0.05).
      Prediction of the response to therapy as early as 1 day after treatment was
      achieved by the quantitative parameter kb (p-value < 0.01), earlier than possible
      by tumor volume quantification. USMI parameters could significantly distinguish
      between clinical responders and non-responders (p-value << 0.01) and correlated
      well with the ex-vivo quantification of VEGFR2 expression and the percentage
      blood vessels area (p-value << 0.01). CONCLUSION: USMI (semi)quantitative
      parameters provide earlier assessment of the response to therapy compared to
      tumor volume, permit early prediction of non-responders, and correlate well with
      ex-vivo angiogenesis biomarkers.

PMID- 30225759
TI  - Adenine Nucleotide Translocase 2 as an Enzyme Related to [18F] FDG Accumulation
      in Various Cancers.
AB  - PURPOSE: Although glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) are known
      as major proteins involved in the molecular mechanisms for accumulating 2-deoxy-2
      [18F]fluoro-D-glucose ([18F]FDG) in cancer cells, sometimes, [18F] FDG
      accumulation cannot be explained by the expression of these two proteins. We
      investigated the involvement of adenine nucleotide translocase 2 (ANT2), which
      catalyzes ADP/ATP exchange at the mitochondrial inner membrane, in [18F] FDG
      accumulation. PROCEDURES: ANT2 expression was evaluated in various cancer cell
      lines and human cancer tissues (microarrays) using western blot and
      immunohistochemical (IHC) staining, respectively. The expression levels of ANT2
      were compared to [18F] FDG accumulation and pathologic findings, including
      differentiation grade. Additionally, we modulated ANT2 expression levels using
      ANT2 siRNA and an ANT2 expression vector in cancer cells and murine xenografted
      tumors. RESULTS: [18F] FDG accumulation correlated with ANT2 expression in
      various cancer cell lines; this was not explained by GLUT1 and/or HK2 expression.
      At both the cell and tissue levels, ANT2 expression was high in less
      differentiated or more malignant type of cancers. [18F] FDG accumulation changed
      according to the modulation of the ANT2 expression level. CONCLUSION: In various
      cancer cells and tissues, the expression levels of ANT2 explained [18F] FDG
      accumulation better than those of GLUT1 and HK2. ANT2 can be used as a marker of
      dedifferentiated pathology and aggressiveness of cancer.

PMID- 30225760
TI  - Correlation of Tumor Perfusion Between Carbon-13 Imaging with Hyperpolarized
      Pyruvate and Dynamic Susceptibility Contrast MRI in Pre-Clinical Model of
      Glioblastoma.
AB  - PURPOSE: The purpose of this study was to compare C-13 imaging parameters with
      hyperpolarized [1-13C]pyruvate with conventional gadolinium (Gd)-based perfusion
      weighted imaging using an orthotopic xenograft model of human glioblastoma
      multiforme (GBM). PROCEDURES: C-13 3D magnetic resonance spectroscopic imaging
      (MRSI) data were obtained from 14 tumor-bearing rats after the injection of
      hyperpolarized [1-13C]pyruvate at a 3T scanner. Dynamic susceptibility contrast
      (DSC) perfusion-weighted MR images were obtained following intravenous
      administration of Gd-DTPA. Normalized lactate, pyruvate, total carbon, and
      lactate to pyruvate ratio from C-13 MRSI data were compared with normalized peak
      height and percent recovery of DeltaR2* curve from the DSC images in the voxels
      containing tumor using a Pearson's linear correlation. RESULTS: Normalized peak
      height from DSC imaging showed substantial correlations with normalized lactate
      (r = 0.6, p = 0.02) and total carbon (r = 0.6, p = 0.02) from hyperpolarized C-13
      MRSI data. CONCLUSIONS: Since the peak height in the DeltaR2* curve from DSC data
      is related to the extent of blood volume, these hyperpolarized C-13 imaging
      parameters may be used to assess blood volume in rodent intracranial xenograft
      models of GBM.

PMID- 30225761
TI  - Prognostic Value of Early Evaluation of Left Ventricular Dyssynchrony After
      Myocardial Infarction.
AB  - PURPOSE: Dispersion in the contraction of the normally coordinate ventricular
      system, referred to as left ventricular (LV) dyssynchrony, is constantly observed
      at different grades of severity after myocardial infarction (MI). We aimed to
      investigate the prognostic value of early dyssynchrony in adverse cardiac events
      after MI in a rat model using the quantified gated single photon emission
      tomography (SPECT; QGS) software. PROCEDURES: After thoracotomy, the left
      coronary arteries of 16 rats were occluded and reperfused. SPECT was performed
      with [99m Tc]methoxyisobutylisonitrile 3 days, 1 week, 2 weeks, 4 weeks, and 8
      weeks after MI. The phase analysis parameters including mean phase standard
      deviation (PSD), bandwidth (BW), entropy, and LV function were analyzed by the
      QGS software. A receiver operating characteristic curve was used to explore the
      predictors for cardiac death and severe cardiac failure (ejection fraction [EF] <
      35 %). A Kaplan-Meier event-free survival analysis, univariate, and multivariate
      Cox proportional hazards regression analyses were conducted. RESULTS: Four rats
      had died, whereas another four rats presented with severe heart failure. LV end
      diastolic volume was increased during follow-up, but no significant changes were
      noted in the other parameters. The prognosis of rats with lower EF and higher end
      diastolic and end-systolic volumes (ESV), PSD, BW, and entropy at 3 days after MI
      was poor. Adverse cardiac events were associated with lower EF (relative risk
      [RR] 13.1, 95 % confidence Interval [CI]: 2.1-259.9, P = 0.003), higher ESV (RR
      6.4, CI 1.4-45.9, P = 0.01), and higher entropy (RR 4.3, 95 % CI: 1.0-21.8, P =
      0.04) by univariate analysis. Multivariate analysis showed that lower EF was the
      most powerful independent predictor of adverse cardiac events (RR 16.0, CI 1.1
      429.2, P = 0.03). CONCLUSIONS: Severe early dyssynchrony evaluated by QGS after
      MI could predict cardiac events in the rat model in the same way as other cardiac
      function parameters including EF and ESV. The early assessment of dyssynchrony
      after MI may provide helpful information for the prediction of cardiac events in
      the future.

PMID- 30225762
TI  - The Effect of Religious Psychotherapy Emphasizing the Importance of Prayers on
      Mental Health and Pain in Cancer Patients.
AB  - The religious aspect is the most important aspect of the human nature that helps
      the human achieve the meaning and purpose of life as well as playing a very
      important role in the health of patients. This study aimed to determine the
      effect of religious psychotherapy emphasizing the importance of prayers on mental
      health and pain in cancer patients. This study is a clinical trial that was
      conducted in 2017 in Yasuj, Iran. According to the purpose of the study, the
      patients were randomly assigned into two experimental and control groups. Prayers
      15 and 23 of the SahifehSajjadiyeh book were read at the beginning of the
      treatment sessions, and the patients were asked to pay attention to the meaning
      of prayer. The data were analyzed using SPSS 16 software. Before implementing the
      intervention, the mean and standard deviation of mental health score of the
      patients in the experimental and control groups were equal to 16.40 (2.21) and
      16.56 (1.56). But after implementing the intervention, the mean and standard
      deviation of mental health score were equal to 11.24 (2.93) and 16.82 (1.83)
      which illustrates a significant statistical increase. Implementing the supportive
      spiritual intervention has been tested to enhance the mental health and reduce
      the pain of patients in the experimental group. Regarding this improvement, it is
      suggested a religious intervention be implemented to increase these patients'
      health in a participatory way.

PMID- 30225763
TI  - The rs2228570 Variant of the Vitamin D Receptor Gene is Associated with Essential
      Tremor.

PMID- 30225765
TI  - Parkinson's Disease Risk Variant rs1109303 Regulates the Expression of INPP5K and
      CRK in Human Brain.

PMID- 30225764
TI  - Cortical Inflammation is Increased in a DSS-Induced Colitis Mouse Model.
AB  - While inflammatory bowel disease (IBD) might be a risk factor in the development
      of brain dysfunctions, the underlying mechanisms are largely unknown. Here, mice
      were treated with 5% dextran sodium sulfate (DSS) in drinking water and
      sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation
      of the IL-6 and TNF-alpha levels in cortical tissue. However, the endotoxin
      concentration in plasma and brain of mice with DSS-induced colitis showed a
      rising trend, but with no significant difference. We also found significant
      activation of microglial cells and reduction in occludin and claudin-5 expression
      in the brain tissue after DSS-induced colitis. These results suggested that DSS
      induced colitis increases systemic inflammation which then results in cortical
      inflammation via up-regulation of serum cytokines. Here, we provide new
      information on the impact of colitis on the outcomes of cortical inflammation.

PMID- 30225766
TI  - The Art of Observation and the Observation of Art: Zadig in the Twenty-first
      Century.
AB  - Astute observation is a fundamental component of the art of medicine. Yet most
      schools and residencies offer little formal teaching of this skill, with some
      outsourcing the entire subject matter to art museums and instructors. Curiously,
      it was nineteenth century medicine that may have provided the conceptual
      framework for what is now known as Visual Thinking Strategy, the technique used
      by many art-based programs in order to teach observation. We suggest that the
      time is ripe for medicine to regain ownership of the teaching of this skill, not
      only because it may enhance clinical care but also because only the eyes of a
      skilled physician can best interpret crucial medical details. To this end, we
      shall revisit both the method of Zadig, which William Osler practiced and taught
      to his students, and its application to the observation of art first pioneered by
      the Italian physician Giovanni Morelli. As an example of this skill, we shall use
      focused observation to decode a fifteenth century portrait that hangs at the
      Philadelphia Museum of Art, thus turning a seemingly non-descript Renaissance
      painting into a treasure trove of personal, social, and medical information.

PMID- 30225767
TI  - General Internists in Pursuit of Diagnostic Excellence.

PMID- 30225768
TI  - Diagnosis and Management of Genetic Iron Overload Disorders.
AB  - Iron overload disorders lead to excess iron deposition in the body, which can
      occur as a result of genetic or secondary causes. Genetic iron overload, referred
      to as hereditary hemochromatosis, may present as a common autosomal recessive
      mutation or as one of several uncommon mutations. Secondary iron overload may
      result from frequent blood transfusions, exogenous iron intake, or certain
      hematological diseases such as dyserythropoietic syndrome or chronic hemolytic
      anemia. Iron overload may be asymptomatic, or may present with significant
      diseases of the liver, heart, endocrine glands, joints, or other organs. If
      treated appropriately prior to end-organ damage, life expectancy has been shown
      to be similar compared to matched populations. Alongside clinical assessment,
      diagnostic studies involve blood tests, imaging, and in some cases liver biopsy.
      The mainstay of therapy is periodic phlebotomy, although oral chelation is an
      option for selected patients.

PMID- 30225769
TI  - Identifying Latent Subgroups of High-Risk Patients Using Risk Score Trajectories.
AB  - OBJECTIVE: Many healthcare systems employ population-based risk scores to
      prospectively identify patients at high risk of poor outcomes, but it is unclear
      whether single point-in-time scores adequately represent future risk. We sought
      to identify and characterize latent subgroups of high-risk patients based on risk
      score trajectories. STUDY DESIGN: Observational study of 7289 patients discharged
      from Veterans Health Administration (VA) hospitals during a 1-week period in
      November 2012 and categorized in the top 5th percentile of risk for
      hospitalization. METHODS: Using VA administrative data, we calculated weekly risk
      scores using the validated Care Assessment Needs model, reflecting the predicted
      probability of hospitalization. We applied the non-parametric k-means algorithm
      to identify latent subgroups of patients based on the trajectory of patients'
      hospitalization probability over a 2-year period. We then compared baseline
      sociodemographic characteristics, comorbidities, health service use, and social
      instability markers between identified latent subgroups. RESULTS: The best
      fitting model identified two subgroups: moderately high and persistently high
      risk. The moderately high subgroup included 65% of patients and was characterized
      by moderate subgroup-level hospitalization probability decreasing from 0.22 to
      0.10 between weeks 1 and 66, then remaining constant through the study end. The
      persistently high subgroup, comprising the remaining 35% of patients, had a
      subgroup-level probability increasing from 0.38 to 0.41 between weeks 1 and 52,
      and declining to 0.30 at study end. Persistently high-risk patients were older,
      had higher prevalence of social instability and comorbidities, and used more
      health services. CONCLUSIONS: On average, one third of patients initially
      identified as high risk stayed at very high risk over a 2-year follow-up period,
      while risk for the other two thirds decreased to a moderately high level. This
      suggests that multiple approaches may be needed to address high-risk patient
      needs longitudinally or intermittently.

PMID- 30225770
TI  - [Renal functional diagnostics using magnetic resonance imaging].
AB  - Due to progress in the development of sequences and techniques magnetic resonance
      imaging (MRI) methods, such as functional MR urography (fMRU), arterial spin
      labeling (ASL), diffusion-weighted imaging (DWI), diffusion tension imaging (DTI)
      and blood oxygen level dependent MRI (BOLD-MRI) have become available for renal
      functional evaluation. In recent years research of these imaging techniques has
      demonstrated that they provide valid functional data with respect to renal
      perfusion, oxygenation and interstitial diffusion as well as glomerular
      filtration and the extent of an obstructive uropathy. Many pathophysiological
      renal processes, e. g. in transplanted kidneys, in the setting of chronic kidney
      disease and in the diagnostics of renal tumors, can therefore be fully evaluated.
      The fMRU, which enables a reliable assessment of renal function combined with
      high-resolution morphological evaluation of the kidneys and the entire urinary
      tract, has already become an inherent component in the clinical setting, at least
      in specialized pediatric radiology centers. To establish the new imaging methods
      in the clinical routine, further technical improvements and large-scale
      prospective clinical studies are necessary to validate the determined functional
      parameters, to generate standard protocols and to unify and facilitate data post
      processing.

PMID- 30225771
TI  - [What do orthopedic and trauma surgeons expect from radiologists when
      interpreting imaging of the elbow?]
AB  - CLINICAL ISSUE: The elbow is a complex joint with a multitude of acute and
      chronic pathologies. In addition to the clinical examination, radiological
      diagnostics play a decisive role in the further therapeutic management.
      DIAGNOSTIC WORK-UP/PERFORMANCE: While acute traumatic injuries often present with
      obvious structural changes and the need for rapid treatment decisions, chronic
      processes can present with less evident alterations. Especially in these cases
      there is a need for clear communication between the treating physician and the
      radiologist with respect to managing optimal imaging as the basis for a certain
      diagnosis and therefore optimal treatment. Basic prerequisites on both sides are
      detailed knowledge of all elbow pathologies, classifications and the spectrum of
      radiological diagnostic imaging. ACHIEVEMENTS/PRACTICAL RECOMMENDATIONS: From the
      point of view of orthopedic surgeons the radiologist is responsible for the
      correct performance and interpretation of the necessary imaging procedures. The
      aim of this article is to give an overview of important aspects in the imaging of
      typical orthopedic/traumatic pathologies.

PMID- 30225772
TI  - Toward standardization of valve-sparing root replacement and annuloplasty.
AB  - INTRODUCTION: The current guidelines for surgical intervention of aortic
      regurgitation were developed by assuming aortic valve replacement. However, when
      aortic valve repair is considered, earlier intervention may provide more durable
      repair. Standardization of the procedures may be required to achieve stable
      outcomes. The possibility of standardization of valve-sparing root replacement
      (VSRR) and annuloplasty will be discussed. METHODS AND RESULTS: The differences
      between the two VSRRs have decreased with technical modifications, reimplantation
      using a graft with sinuses, and remodeling with annuloplasty. The minor
      differences are the maintenance of root distensibility, less root dissection,
      shorter procedure time, and higher risk of bleeding in the latter. Stable
      outcomes may be expected by choosing the appropriate graft size according to the
      root dimensions in the former. In the latter, postoperative commissure height
      depends on the skill of the surgeon, which can be resolved using a graft with
      sinuses. There is still controversy regarding the equal arrangement of the
      commissure heights and angle, but it has been accepted in clinical use provided
      that postoperative effective heights of each cusp are set equally. External
      suture annuloplasty maintains the advantages of remodeling because it requires
      less root dissection and a shorter procedure time. It can accurately predict
      postoperative annulus diameter. External ring annuloplasty can stabilize the
      basal ring exactly, but it is time-consuming and postoperative annulus diameter
      cannot be predicted accurately. CONCLUSIONS: Standardization of VSRR may be
      feasible, and VSRR is expected to be more widely adopted, which will improve the
      guidelines.

PMID- 30225773
TI  - Prognosis and treatment outcomes of central neurocytomas: clinical interrogation
      based on a single center experience.
AB  - INTRODUCTION: Central neurocytoma (CN) is a very rare neuronal neoplasm. The
      clinical implications of the potential prognostic factors for these lesions,
      including tumor atypia, have therefore not been clarified. METHODS: Forty CN
      patients were enrolled and reclassified as typical or atypical in accordance with
      an MIB-1 labeling index (LI) of above and below 2%. RESULTS: We classified our
      retrospective study cohort as 21 (52.5%) typical and 19 (47.5%) atypical CN
      cases. No significant differences were found in terms of sex, mean age, mean
      tumor size or tumor location between these groups. Recurrences occurred in 2
      (9.5%) typical and 6 (33.3%) atypical cases. The typical CN 2-,3- and 5-year PFS
      rates were 100%, 100%, 92.3%, and those for the atypical group were 93.8%, 78.1%,
      65.1%, respectively (p = 0.02). The PFS rates did not statistically differ by
      treatment modality (gross total resection alone, subtotal resection (STR) alone
      and STR plus radiation therapy (RT) or radiosurgery (RS)) either in the whole
      cohort (p = 0.75) or in the typical CN and atypical CN subgroups (p = 0.45 and
      0.98, respectively). An atypical histology was the only prognostic indicator of
      recurrence by univariate analysis (hazard ratio: 5.40, p = 0.04). CONCLUSIONS: An
      atypical lesion (MIB-LI > 2%) is an important prognostic indicator in CN. The
      clinical implications of the extent of resection for CN patients are still
      debatable. The use of STR plus RT or RS may be a viable treatment strategy for CN
      but different therapeutic and follow-up approaches for atypical CN will be
      needed.

PMID- 30225774
TI  - Sprouty2-a Novel Therapeutic Target in the Nervous System?
AB  - Clinical trials applying growth factors to alleviate symptoms of patients with
      neurological disorders have largely been unsuccessful in the past. As an
      alternative approach, growth factor receptors or components of their signal
      transduction machinery may be targeted directly. In recent years, the search for
      intracellular signaling integrator downstream of receptor tyrosine kinases
      provided valuable novel substrates. Among them are the Sprouty proteins which
      mainly act as inhibitors of growth factor-dependent neuronal and glial signaling
      pathways. In this review, we summarize the role of Sprouties in the lesioned
      central and peripheral nervous system with particular reference to Sprouty2 that
      is upregulated in various experimental models of neuronal degeneration and
      regeneration. Increased synthesis under pathological conditions makes Sprouty2 an
      attractive pharmacological target to enhance intracellular signaling activities,
      notably the ERK pathway, in affected neurons or activated astrocytes.
      Interestingly, high Sprouty2 levels are also found in malignant glioma cells. We
      recently demonstrated that abrogating Sprouty2 function strongly inhibits
      intracranial tumor growth and leads to significantly prolonged survival of
      glioblastoma bearing mice by induction of ERK-dependent DNA replication stress.
      On the contrary, knockdown of Sprouty proteins increases proliferation of
      activated astrocytes and, consequently, reduces secondary brain damage in
      neuronal lesion models such as kainic acid-induced epilepsy or endothelin-induced
      ischemia. Furthermore, downregulation of Sprouty2 improves nerve regeneration in
      the lesioned peripheral nervous system. Taken together, targeting Sprouties as
      intracellular inhibitors of the ERK pathway holds great promise for the treatment
      of various neurological disorders including gliomas. Since the protein lacks
      enzymatic activities, it will be difficult to develop chemical compounds capable
      to directly and specifically modulate Sprouty functions. However, interfering
      with Sprouty expression by gene therapy or siRNA treatment provides a realistic
      approach to evaluate the therapeutic potential of indirectly stimulating ERK
      activities in neurological disease.

PMID- 30225775
TI  - Fragile X and APP: a Decade in Review, a Vision for the Future.
AB  - Fragile X syndrome (FXS) is a devastating developmental disability that has
      profound effects on cognition, behavior, and seizure susceptibility. There are
      currently no treatments that target the underlying cause of the disorder, and
      recent clinical trials have been unsuccessful. In 2007, seminal work demonstrated
      that amyloid-beta protein precursor (APP) is dysregulated in Fmr1KO mice through
      a metabotropic glutamate receptor 5 (mGluR5)-dependent pathway. These findings
      raise the hypotheses that: (1) APP and/or APP metabolites are potential
      therapeutic targets as well as biomarkers for FXS and (2) mGluR5 inhibitors may
      be beneficial in the treatment of Alzheimer's disease. Herein, advances in the
      field over the past decade that have reproduced and greatly expanded upon these
      original findings are reviewed, and required experimentation to validate APP
      metabolites as potential disease biomarkers as well as therapeutic targets for
      FXS are discussed.

PMID- 30225776
TI  - Amyloid beta Peptide Compromises Neural Stem Cell Fate by Irreversibly Disturbing
      Mitochondrial Oxidative State and Blocking Mitochondrial Biogenesis and Dynamics.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease and is
      characterized by the accumulation of amyloid beta peptide (Abeta). Although most
      AD mouse models present a decline in neurogenesis, they express mutated genes
      which regulate neurogenesis per se and are not present in most AD patients, thus
      masking the real impact of Abeta on adult neurogenesis. Mitochondrion, a well
      known target of Abeta in neurons, is a main regulator of neural stem cell (NSC)
      fate. Here, we aimed to investigate the impact of Abeta on NSC mitochondria and
      cell fate decisions, namely whether and how Abeta affects neurogenesis. NSC fate
      and mitochondrial parameters, including biogenesis, dynamics, and oxidative
      stress, were evaluated. Our results showed that Abeta impaired NSC viability and
      proliferation and indirectly blocked neurogenic differentiation, by disrupting
      mitochondrial signaling of self-renewing NSCs. Importantly, Abeta decreased ATP
      levels, generated oxidative stress, and affected the radical scavenger system
      through SOD2 and SIRT3. Abeta also reduced mtDNA and mitochondrial biogenesis
      proteins, such as Tfam, PGC-1alpha, and NRF1, and inhibited activation of PGC
      1alpha-positive regulator CREB. Moreover, Abeta triggered mitochondrial
      fragmentation in self-renewing NSCs and reduced mitochondrial fusion proteins,
      such as Mfn2 and ERRalpha. Notably, Abeta compromised NSC commitment and survival
      by irreversibly impairing mitochondria and thwarting any neurogenic rescue
      through mitochondrial biogenesis, dynamics, or radical scavenger system.
      Altogether, this study brings new perspective to rethink the molecular targets
      relevant for endogenous NSC-based strategies in AD.

PMID- 30225778
TI  - Evaluation of Nasal Inlet Ports Having Simplified Geometry for the Pharmacopeial
      Assessment of Mass Fraction of Dose Likely to Penetrate Beyond the Nasopharynx: a
      Preliminary Investigation.
AB  - Nasal cavity breakthrough to the airways of the lungs is associated with nasally
      inhaled droplets whose size is smaller than ca. 10 MUm aerodynamic diameter that
      behave as an aerosol rather than a spray in terms of their transport. The purpose
      of the present laboratory-based study was to evaluate a nasal product quality
      control procedure involving a new inlet for the quantification of mass of such
      droplets emitted by commercially available aqueous nasal spray pump products by
      cascade impactor. This inlet is more representative of the adult nasal vestibule
      in terms of entry angle for the spray as well as internal volume for plume
      expansion. Sampling was also undertaken via a spherical 1-L glass expansion
      vessel as inlet, previously established for quantification of these aerosol
      droplets. The selected solution- and suspension-formulated products containing
      azelastine and fluticasone propionate respectively were shown to contain < 1% of
      the total spray mass per actuation associated with droplets < 14.1 MUm
      aerodynamic diameter. These measurements were consistent with laser diffraction
      based measurements of the entire droplet size distribution. Comparable measures
      of aerosol droplet mass fraction were obtained when the spray was sampled by the
      cascade impactor method using either the 1-L glass expansion chamber or the new
      metal inlet as entry for the spray produced by either product evaluated. We
      conclude that the metal inlet has the potential to be adopted as a suitable
      induction port in the assessment of nasal product quality, where currently no
      standardized inlet exists.

PMID- 30225779
TI  - Development and Characterization of Novel Medicated Nanofiber for the Treatment
      of Periodontitis.
AB  - Periodontitis is a common microbial infection that involves pocket formation due
      to the destruction of periodontal ligament. The present work is oriented to
      provide a holistic approach for the treatment of periodontitis comprising
      localized delivery of nanometric hydroxyapatite as a reinforcing filler and
      silver-metronidazole as periodontal pocket disinfectant adjunct to current
      periodontal therapy because of its broad-spectrum antimicrobial activity and low
      systemic toxicity. In the present work, electrospinning technique was used to
      prepare medicated nanofiber enriched with antibacterial-hydroxyapatite layers for
      dental application. The optimized formulation was characterized by SEM, FTIR,
      DSC, XRD, etc. Safety assessment and therapeutic potential of optimized
      formulation was evaluated in both in vitro and in vivo animal models. The newly
      synthesized complex (silver-metronidazole) exhibited higher antibacterial
      activity against the selected strain over the referenced silver and
      metronidazole. Results of in vitro studies suggested good compatibility of the
      metal complex with the polymer matrix. The drug release behavior from optimized
      formulation shows constant in vitro release behavior. Both in vitro and in vivo
      studies show broad-spectrum antimicrobial activity of the metal complex and
      demonstrate the potential of biomimetic nano-hydroxyapatite for filling
      periodontal defects. All these observations indicated that the above formulation
      could play a useful role in the treatment of periodontitis. Graphical Abstract ?.

PMID- 30225780
TI  - The influence of thought probes on performance: Does the mind wander more if you
      ask it?
AB  - Mind-wandering has emerged in the past decade as a popular topic in many areas of
      psychological research. Numerous studies have demonstrated the potential costs
      and benefits of mind-wandering in relation to ongoing task performance, along
      with more recent work examining the nature of different types of mind-wandering.
      A common method of measuring mind-wandering in laboratory research is to embed
      self-report thought probes at random intervals within an ongoing task. However, a
      critical issue to determine is whether or not the presence of the thought probes
      fundamentally alters how an individual typically performs on the task. In the
      current study, N = 149 participants completed a sustained attention to response
      task (SART) with and without the presence of mind-wandering thought probes. In
      addition, participants completed operation and symmetry span measures of working
      memory capacity, as several studies have examined the relationship between
      individual differences in working memory capacity and mind-wandering using
      thought probes on the SART. The results indicate that SART performance does not
      differ whether thought probes are included or not. Individuals higher in working
      memory capacity produced better SART performance in the conditions with and
      without thought probes. In addition, individuals in working memory capacity were
      negatively correlated with mind-wandering frequency. The results indicate that
      thought probe measurement is a non-reactive method to measure mind-wandering in
      attention and inhibition tasks.

PMID- 30225777
TI  - Potential Role of Selective Serotonin Reuptake Inhibitors in Improving Functional
      Outcome after Stroke.
AB  - The great advances in acute stroke treatment during the last decades have changed
      life after stroke considerably. However, the use of intravenous thrombolysis and
      endovascular thrombectomy is limited by a relatively narrow time window or
      contraindications for treatment. Further, patients receiving acute reperfusion
      therapies may still have cognitive and emotional complications due to underlying
      brain infarcts even though physical problems may almost disappear. Consequently,
      stroke is still a frequent cause of adult disability and death worldwide, and an
      effort to identify additional treatments to enhance recovery, preferably also
      feasible in the time after the acute phase, is warranted. Albeit several drugs
      and treatment modalities have been studied for their potential to enhance
      recovery after stroke, no treatment has unambiguously proven to potentiate the
      rehabilitation process. A promising candidate for pharmacological treatment is
      selective serotonin reuptake inhibitors (SSRIs), a group of commonly used
      antidepressants that may also possess neuro-regenerative properties. The current
      paper reviews the evidence for SSRIs as potential enhancers of stroke recovery
      and discusses the potential mechanisms behind the effects reported and the
      implications for the management of patients post-stoke, including potential
      adverse events and drug-drug interactions.

PMID- 30225781
TI  - Down-regulation of lncTCF7 inhibits cell migration and invasion in colorectal
      cancer via inhibiting TCF7 expression.
AB  - The prognosis of colorectal cancer (CRC) is still very poor, owing to the high
      incidence of metastasis. Long noncoding RNA TCF7 (lncTCF7) has been shown to play
      critical roles in human CRC development and progression, but the molecular
      mechanisms of lncTCF7 in CRC are still unknown. This study aimed to explore the
      functions and molecular mechanisms of lncTCF7 on the migration and invasion of
      CRC cells. Notably, lncTCF7 was highly expressed in CRC cell lines relative to
      normal colonic epithelial cells. LncTCF7 knockdown significantly inhibited
      migration and invasion of CRC cells. In addition, TCF7 was highly expressed in
      CRC cell lines relative to that in normal colonic epithelial cells and its
      expression was significantly decreased in CRC cells transfected with si-lncTCF7.
      RNA immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter
      assays showed that LncTCF7 recruits BAF170 to activate the TCF7 promoter and
      regulate TCF7 expression. TCF7 overexpression could promote migration and
      invasion in CRC cells transfected with si-lncTCF7, which reversed the effect of
      lncTCF7 on the migration and invasion of CRC cells. In conclusion, our data
      indicate that the downregulation of lncTCF7 significantly inhibits migration and
      invasion of CRC cells by inhibiting TCF7 expression, suggesting that lncTCF7 may
      be a potential target for CRC therapy.

PMID- 30225782
TI  - Is the Film Unbreakable Really About PTSD with Dissociation?

PMID- 30225783
TI  - Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated
      with Ipilimumab.
AB  - Ipilimumab was the first immunotherapy approved for metastatic melanoma in
      decades and is currently registered as a second-line treatment. However, new
      immunotherapies, in combination with ipilimumab, offer even better clinical
      outcomes for patients compared with single-agent treatments, at the expense of
      improved toxicity. The aim of this study was to evaluate the feasibility of
      ipilimumab outside the clinical trials and to identify survival predictors for
      treatment benefit. Data were collected on 47 advanced melanoma patients treated
      with ipilimumab between 2010 and 2015 at a single center. Association of clinical
      characteristics (including primary tumor characteristics), serum lactate
      dehydrogenase (LDH), erythrocyte sedimentation rate, absolute eosinophil,
      lymphocyte, and neutrophil count, neutrophil/lymphocyte and eosinophil/lymphocyte
      ratio with toxicity and clinical outcome were assessed using univariate and
      multivariate analysis. Median progression-free survival at a median follow-up of
      10 months was 2.7 months and median overall survival was 9.8 months. Objective
      response was observed in 17% of patients and the disease control rate at week 24
      was 40%. The 1- and 2-year survival rates documented were 40 and 28%,
      respectively. Significant association between high LDH level (>1.5* upper limit
      of normal) and decreased overall survival was demonstrated in uni- and
      multivariate analysis (hazard ratio [HR]: 3.554, 95% CI: 1.225-10.306, p =
      0.019). Neither biomarkers nor clinical outcome were associated with toxicity.
      Using baseline serum LDH to identify patients most likely to benefit from
      ipilimumab therapy could serve as a simple and inexpensive biomarker of clinical
      outcome.

PMID- 30225784
TI  - The Clinicopathological and Molecular Associations of PD-L1 Expression in Non
      small Cell Lung Cancer: Analysis of a Series of 10,005 Cases Tested with the 22C3
      Assay.
AB  - PD-L1 expression testing is mandatory prior to pembrolizumab prescription in non
      small cell lung cancer. Our service offers PD-L1 testing using the PD-L1 IHC 22C3
      pharmDx assay, in parallel with EGFR, ALK, ROS1 and (in some cases) KRAS testing.
      We correlate PD-L1 expression in 10,005 tumours with patient age and sex, with
      tumour histological subtypes, with the sampling modality and type of tissue, and
      with the presence of other molecular alterations. PD-L1 expression testing was
      performed using the aforementioned assay; tumour proportion scores (TPS) of 1 and
      50% were taken as cut-offs for low and high positivity, respectively. EGFR
      testing was performed using the cobas(r) EGFR Mutation Test v2. ALK testing was
      performed using the VENTANA ALK (D5F3) CDx Assay. KRAS testing was performed
      using pyrosequencing. TPS <1% was seen in 44.4% of tumours, 1-49% in 25.0% and >=
      50% in 30.6%. We identified no significant relationship with age. Female patients
      were slightly more likely to express PD-L1. Poorly-differentiated tumour
      histology and ALK translocation were significantly associated with PD-L1
      expression. Rare EGFR mutations tended to be associated with PD-L1 expression.
      Pleural and nodal metastases were more likely to express PD-L1 than primary
      tumours, but biopsy and cytological specimens did not show different PD-L1
      expression rates. Our data show that the means of acquiring a tumour sample
      (biopsy versus cytology) does not have a significant impact on PD-L1 expression.
      However, we found that certain metastatic sites were associated with
      significantly higher expression rates, which has substantial implications for
      selection of tissue for testing.

PMID- 30225785
TI  - EGG DWPack: System for Multi-Channel Electrogastrographic Signals Recording and
      Analysis.
AB  - Electrogastrography (EGG) is a non-invasive examination method for investigating
      the myolectrical activity of a stomach. Nowadays, abdominal surface
      electrogastrography is the one of methods of stomach examination that is used for
      diagnosing patients with chronic intractable nausea, vomiting and gastroparesis.
      The electrogastrographic signals are recorded by using cutaneous electrodes
      placed on the stomach surface. EGG DWPack system is a highly developed and easy
      to use software package for four channel electrogastrography recording and
      analysis. The part of the software for analysis is a MATLAB based software and
      requires the specific ASCII format of the EGG data. The analyzed EGG signals
      could be conditioned with the wide range of sampling frequency and various
      resolutions of analog to digital conversion. Additionally, if the EGG data
      fulfills certain conditions associated with sampling frequency, the software can
      be used to study the basic parameters of heart rate variability (HRV)
      simultaneously with the EGG parameters. The software includes different digital
      filters for the EGG signal extraction and tools for artifacts exclusion. The
      software computes the majority of EGG parameters which are commonly used in a
      clinical practice. The EGG analysis can be made for several adjustable analysis
      settings and various methods, and it can optimize the analysis methods for
      different preferences or requirements. The analysis result can be saved in a MAT
      file, and exported to MS Excel and ASCII files. Validation of the software was
      performed using synthetic and real EGG signals. This paper contains, as an
      example of use, an analysis of four synthetic, and fourteen human 4-channel EGG
      data recording with water, yogurt and a solid meal stimulation. The mean values
      of the dominant frequency for fast, and postprandial stage were found to be
      2.96+/-0.21 cpm (cycle per minute), and 3.05+/-0.33 cpm, respectively. The values
      established in the validation process are consistent with typical human
      physiological values. In addition, the results were compared to outcomes from
      commercial system. The results of validation have proved that EGG DWPack software
      produces reliable outcomes. The software is available for free of charge for
      Windows operating system for the all possible non commercial use.

PMID- 30225786
TI  - The effect of three exercise approaches on health-related quality of life, and
      factors associated with its improvement in chronic whiplash-associated disorders:
      analysis of a randomized controlled trial.
AB  - PURPOSE: The aim was to evaluate whether neck-specific exercise, with (NSEB) or
      without (NSE) a behavioural approach, improves health-related quality of life
      (HRQoL) compared to physical activity prescription (PPA) in chronic whiplash
      associated disorders (WAD) grades 2 and 3. A secondary aim was to identify
      factors associated with HRQoL and HRQoL improvement following exercise
      interventions. METHODS: This is a secondary analysis of a multicentre randomized
      clinical trial. Participants (n = 216) with chronic WAD grades 2 and 3 were
      randomized to 12 weeks of PPA or physiotherapist-led NSE or NSEB. The EQ-5D 3L/EQ
      VAS and SF-36v2 physical (PCS) and mental (MCS) component summaries were
      collected together with several neck-related and psychosocial outcomes at
      baseline, after 3, 6 and 12 months, and were analysed with linear mixed models
      (all time points) and multivariate linear regressions (baseline, 6 months).
      RESULTS: NSE/NSEB resulted in better outcomes than PPA (EQ-VAS and SF-36 PCS,
      both groups, p < 0.01) but not in a higher EQ-5D score. Improvement over time was
      seen in EQ-5D/EQ-VAS for the NSEB group (p < 0.01), and for NSE/NSEB as measured
      with the PCS (p < 0.01). Factors associated with baseline HRQoL and change to 6
      months in HRQoL (R2 = 0.38-0.59) were both neck-related and psychosocial (e.g.
      depression, work ability). CONCLUSION: Neck-specific exercise, particularly with
      a behavioural approach, may have a more positive impact on HRQoL than physical
      activity prescription in chronic WAD grades 2 and 3. HRQoL is however complex,
      and other factors also need to be considered. Factors associated with HRQL and
      improvements in HRQoL following exercise are multidimensional. TRIAL REGISTRATION
      NUMBER: ClinicalTrials.gov, No. NCT01528579.

PMID- 30225787
TI  - Health state utility values measured using the EuroQol 5-dimensions questionnaire
      in adults with chronic hepatitis C: a systematic literature review and meta
      analysis.
AB  - PURPOSE: Chronic hepatitis C infection and its treatment can considerably affect
      patients' health-related quality-of-life (HRQoL). This study aimed to identify
      and summarise the current evidence base for health state utility values (HSUVs)
      in patients with chronic hepatitis C infection, generated using the EuroQol 5
      dimensions (EQ-5D) questionnaire. METHODS: MEDLINE, Embase, the Cochrane Library
      and EconLit were searched from database inception through 31 August 2017.
      Eligible studies reported HSUVs elicited using the EQ-5D questionnaire in adults
      with chronic hepatitis C infection. Study quality and risk of bias were assessed.
      RESULTS: Of 1480 records identified, 26 studies were included. The most commonly
      defined health states described different stages of chronic hepatitis C infection
      and specific liver-related disease states, including METAVIR score, compensated
      and decompensated cirrhosis, hepatocellular carcinoma and liver transplantation.
      Patients with higher METAVIR scores tended to have lower EQ-5D scores compared to
      patients with lower METAVIR scores. Patients that achieved sustained virologic
      responses tended to have higher EQ-5D scores compared to those that did not. A
      meta-analysis conducted on three studies confirmed that patients with
      decompensated cirrhosis have significantly lower HSUVs than patients with
      compensated cirrhosis [mean difference - 0.11 (95% CI - 0.19 to - 0.04)],
      implying worse HRQoL. However, there was not sufficient evidence to compare how
      different treatments for chronic hepatitis C infection affect EQ-5D scores.
      CONCLUSIONS: This study provides a summary of EQ-5D HSUVs for patients with
      chronic hepatitis C infection, and demonstrates that clinically important disease
      stages associated with treatment decisions are associated with differences in
      HRQoL.

PMID- 30225788
TI  - Validity of the EQ-5D-5L and EQ-5D-3L in patients with Crohn's disease.
AB  - PURPOSE: The EuroQol five-dimension questionnaire (EQ-5D) is the most commonly
      used instrument to obtain utility values for cost-effectiveness analyses of
      treatments for Crohn's disease (CD). We aimed to compare the measurement
      properties of the two adult versions of EQ-5D (EQ-5D-3L and EQ-5D-5L) in patients
      with CD. METHODS: Between 2016 and 2017, a multicentre cross-sectional survey was
      carried out. Consecutive outpatients with CD completed the 3L, 5L and EQ visual
      analogue scale (VAS). Disease severity was graded by the Crohn's Disease Activity
      Index (CDAI) and Perianal Disease Activity Index (PDAI). The 3L and 5L were
      compared in terms of feasibility, agreement, ceiling effect, redistribution
      properties, discriminatory power, convergent and known-groups validity. RESULTS:
      Two-hundred and six patients (54.9% male, mean age 35 +/- 11 years) participated
      in the survey. For 3L, 25 unique health states were observed versus 59 for the
      5L. The overall ceiling effect decreased from 29.6% (3L) to 25.5% (5L). Absolute
      discriminatory power improved (mean Shannon index 0.84 vs. 1.18). The 3L
      correlated stronger with EQ VAS and CDAI scores, whereas the 5L with PDAI. The 5L
      demonstrated a better known-groups validity on the basis of age, perianal
      fistulas, extraintestinal manifestations and disability. CONCLUSIONS: This is the
      first study to report the impact of CD on quality of life using the EQ-5D-5L
      questionnaire. The 5L seems to perform better than 3L in terms of feasibility,
      ceiling effect, discriminatory power and known-groups validity. Understanding the
      differences in psychometrics between the 3L and 5L is essential as they have
      substantial implications for financial decision-making about CD treatments.

PMID- 30225789
TI  - Ketogenic Diets for Adult Neurological Disorders.
AB  - The current review highlights the evidence supporting the use of ketogenic diet
      therapies in the management of a growing number of neurological disorders in
      adults. An overview of the scientific literature supporting posited mechanisms of
      therapeutic efficacy is presented including effects on neurotransmission,
      oxidative stress, and neuro-inflammation. The clinical evidence supporting
      ketogenic diet use in the management of adult epilepsy, malignant glioma,
      Alzheimer's disease, migraine headache, motor neuron disease, and other
      neurologic disorders is highlighted and reviewed. Lastly, common adverse effects
      of ketogenic therapy in adults, including gastrointestinal symptoms, weight loss,
      and transient dyslipidemia are discussed.

PMID- 30225790
TI  - Inhibition of miR-155 Limits Neuroinflammation and Improves Functional Recovery
      After Experimental Traumatic Brain Injury in Mice.
AB  - Micro-RNAs (miRs) are short, noncoding RNAs that negatively regulate gene
      expression at the post-transcriptional level and have been implicated in the
      pathophysiology of secondary damage after traumatic brain injury (TBI). Among
      miRs linked to inflammation, miR-155 has been implicated as a pro-inflammatory
      factor in a variety of organ systems. We examined the expression profile of miR
      155, following experimental TBI (controlled cortical impact) in adult male
      C57Bl/6 mice, as well as the effects of acute or delayed administration of a miR
      155 antagomir on post-traumatic neuroinflammatory responses and neurological
      recovery. Trauma robustly increased miR-155 expression in the injured cortex over
      7 days. Similar TBI-induced miR-155 expression changes were also found in
      microglia/macrophages isolated from the injured cortex at 7 days post-injury. A
      miR-155 hairpin inhibitor (antagomir; 0.5 nmol), administered
      intracerebroventricularly (ICV) immediately after injury, attenuated
      neuroinflammatory markers at both 1 day and 7 days post-injury and reduced
      impairments in spatial working memory. Delayed ICV infusion of the miR-155
      antagomir (0.5 nmol/day), beginning 24 h post-injury and continuing for 6 days,
      attenuated neuroinflammatory markers at 7 days post-injury and improved motor,
      but not cognitive, function through 28 days. The latter treatment limited NADPH
      oxidase 2 expression changes in microglia/macrophages in the injured cortex and
      reduced cortical lesion volume. In summary, TBI causes a robust and persistent
      neuroinflammatory response that is associated with increased miR-155 expression
      in microglia/macrophages, and miR-155 inhibition reduces post-traumatic
      neuroinflammatory responses and improves neurological recovery. Thus, miR-155 may
      be a therapeutic target for TBI-related neuroinflammation.

PMID- 30225791
TI  - Evaluation of 3K3A-Activated Protein C to Treat Neonatal Hypoxic Ischemic Brain
      Injury in the Spiny Mouse.
AB  - Neonatal hypoxic ischemic encephalopathy (HIE) resulting from intrapartum
      asphyxia is a global problem that causes severe disabilities and up to 1 million
      deaths annually. A variant form of activated protein C, 3K3A-APC, has
      cytoprotective properties that attenuate brain injury in models of adult stroke.
      In this study, we compared the ability of 3K3A-APC and APC (wild-type (wt)) to
      attenuate neonatal brain injury, using the spiny mouse (Acomys cahirinus) model
      of intrapartum asphyxia. Pups were delivered at 38 days of gestation (term = 39
      days), with an intrapartum hypoxic insult of 7.5 min (intrapartum asphyxia
      cohort), or immediate removal from the uterus (control cohort). After 1 h, pups
      received a subcutaneous injection of 3K3A-APC or wild-type APC (wtAPC) at 7
      mg/kg, or vehicle (saline). At 24 h of age, pups were killed and brain tissue was
      collected for measurement of inflammation and cell death using RT-qPCR and
      histopathology. Intrapartum asphyxia increased weight loss, inflammation, and
      apoptosis/necrosis in the newborn brain. 3K3A-APC administration maintained body
      weight and ameliorated an asphyxia-induced increase of TGFbeta1 messenger RNA
      expression in the cerebral cortex, immune cell aggregation in the corpus
      callosum, and cell death in the deep gray matter and hippocampus. In the cortex,
      3K3A-APC appeared to exacerbate the immune response to the hypoxic ischemic
      insult. While wtAPC reduced cell death in the corpus callosum and hippocampus
      following intrapartum asphyxia, it increased markers of neuro-inflammation and
      cell death in control pups. These findings suggest 3K3A-APC administration may be
      a useful therapy to reduce cell death and neonatal brain injury associated with
      HIE.

PMID- 30225792
TI  - Cholecystectomy Vs. Cholecystostomy for the Management of Acute Cholecystitis in
      Elderly Patients.
AB  - BACKGROUND: Data comparing outcomes following cholecystectomy and cholecystostomy
      tube placement (CTP) in elderly patients are lacking. We aimed to compare the
      post-procedural outcomes between cholecystectomy and CTP in elderly patients with
      acute cholecystitis. METHODS: We performed a retrospective, population-based
      analysis using the National Inpatient Sample for the period 2000-2014. Patients
      >= 65 years old admitted with a primary diagnosis of acute cholecystitis and who
      underwent either cholecystectomy or CTP during their hospitalization were
      included. Multivariable linear and logistic regression models were used to
      analyze post-procedural complications, mortality, length of stay, and total
      charges. The effect of procedure type on patient outcomes, stratified by
      acalculous and calculous cholecystitis, was also performed. RESULTS: A total of
      200,915 patients were included, of which 7516 underwent CTP and 193,399 underwent
      cholecystectomy. The median age of patients undergoing CTP and cholecystectomy
      was 80 (IQR 73-87) and 75 (IQR 70-81), respectively. Patients undergoing CTP were
      more likely to have post-procedural infection (OR 2.25; 95% CI 2.07, 2.45),
      bleeding (OR 1.28; 95% CI 1.19, 1.37), and inpatient mortality (OR 9.27; 95% CI
      7.95, 10.81). On average, CTP patients stayed 1.25 days longer (95% CI 1.14,
      1.37) in hospital after the procedure. The benefits of cholecystectomy were
      consistent in patients with acalculous and calculous cholecystitis. CONCLUSIONS:
      Elderly patients with both acalculous and calculous acute cholecystitis managed
      with CTP have higher incidences of post-procedural morbidity and mortality, and
      longer post-procedure length of hospital stay, as compared to cholecystectomy.
      Unless prohibitive surgical risks exist, elderly patients with acute
      cholecystitis should undergo cholecystectomy.

PMID- 30225793
TI  - Prognostic Value of the Number of Lymph Nodes Examined in Patients with Node
      Negative Gastric Cancer.
AB  - BACKGROUND: Our aim was to evaluate the prognostic value of the number of lymph
      nodes examined (eLNs) in patients with node-negative gastric cancer (GC) and
      further to adjust the American Joint Committee on Cancer (AJCC) 8th staging
      system based on the number of eLNs. METHODS: Node-negative GC patients diagnosed
      during 1988-2015 from the Surveillance, Epidemiology, and End Results (SEER)
      database were included. On the basis of a primary cohort of 4159 node-negative GC
      patients, we built the adjusted AJCC 8th staging system, which was then
      internally validated by a bootstrap method, and externally validated with an
      independent cohort of 5565 node-negative GC patients. RESULTS: The median number
      of eLNs was 10. For the training set, the optimal eLNs thresholds were determined
      to be 9 for node-negative GC patients. The adjusted AJCC 8th staging system for
      node-negative GC patients based on the number of eLNs had a significantly higher
      Harrell's concordance index than the initial AJCC 8th staging system (C-index,
      0.635 versus 0.616; P < 0.001). Thus, the adjusted AJCC 8th staging system had
      superior prognostic stratification. Similar results were found in the validation
      set. CONCLUSIONS: For node-negative GC patients in the United States, the
      adjusted AJCC 8th staging system based on the number of eLNs predicted survival
      more accurately and discriminatively.

PMID- 30225795
TI  - CT Scan Findings Can Predict the Safety of Delayed Appendectomy for Acute
      Appendicitis.
AB  - BACKGROUND: The relationship between duration of in-hospital waiting time and
      outcomes from appendectomy in patients with suspected appendicitis remains
      equivocal. The aim of this study was to investigate the influence of in-hospital
      waiting time on perforation rates and clinical outcomes in patients with
      suspected appendicitis who underwent appendectomy. METHODS: A retrospective
      review of 5956 patients who underwent appendectomy at a single institution from
      January 2008 to December 2016 was performed. Patients were separated into two
      groups based on the duration from hospital arrival to surgery: patients with an
      in-hospital waiting time <= 12 h (no-delay group; n = 5287) and those with an in
      hospital waiting time > 12 h (delayed group; n = 669). One-to-one propensity
      score matching (n = 421 per group) was performed to compare perforation rates and
      postoperative outcomes between the groups. RESULTS: After propensity score
      matching, an in-hospital waiting time > 12 h was not associated with increased
      rates of perforation and significant complications, such as wound infection and
      abscess. However, in the matched cohorts and in the patients whose initial CT
      scans suggested perforated appendicitis, the delayed group had a higher risk of
      developing postoperative ileus (OR 9.18, 95% CI 1.16-72.74, p = 0.021; OR 2.17,
      95% CI 1.03-4.59, p = 0.048, respectively) and longer postoperative length of
      hospital stay (87.38 vs. 79.07 h, p = 0.008; 161.61 vs. 130.87 h, p < 0.001,
      respectively) than the no-delay group. CONCLUSIONS: Our results indicate that a >
      12-h in-hospital waiting time to surgery for appendicitis presents very little
      risk to the patient. However, the surgeon needs to carefully weigh the "safety"
      of a delay to surgery for appendicitis in patients whose initial CT scans
      suggested perforated appendicitis.

PMID- 30225794
TI  - Major Complications Independently Increase Long-Term Mortality After
      Pancreatoduodenectomy for Cancer.
AB  - BACKGROUND: Postoperative major morbidity has been associated with worse survival
      gastrointestinal tumors. This association remains controversial in pancreatic
      cancer (PC). We analyzed whether major complications after surgical resection
      affect long-term survival. METHODS: Records of all PC patients resected from 2007
      to 2015 were reviewed. Major morbidity was defined as any grade-3 or higher 30
      day complications, per the Clavien-Dindo Classification. Patients who died within
      90 days after surgery were excluded from survival analysis. RESULTS: Of 616
      patients, 81.7% underwent pancreatoduodenectomy (PD) and 18.3% distal
      pancreatectomy (DP). Major complications occurred in 19.1% after PD and 15.9%
      after DP. In patients who survived > 90 days, the likelihood of receiving
      adjuvant treatment was 43.9% if major complications had occurred, vs. 68.5% if
      not (p < 0.001), and those who received it started the treatment median 10 days
      later compared with uncomplicated patients (median 60 days (50-72) vs. 50 days
      (41-61), p = 0.001). By univariate analysis, in addition to the conventional
      pathology-related prognostic determinants and the receipt of adjuvant treatment,
      major complications worsened long-term survival after PD (median OS 26 months vs.
      15, p = 0.008). A difference was also seen after DP, but it did not reach
      statistical significance, likely related to the small sample size (median OS 33
      months vs. 18, p = 0.189). At multivariate analysis for PD, major postoperative
      complications remained independently associated with worse survival [HR 1.37,
      95%CI (1.01-1.86)]. CONCLUSIONS: Major surgical complications after
      pancreaticoduodenectomy are associated with worse long-term survival in
      pancreatic cancer. This effect is independent of the receipt of adjuvant
      treatment.

PMID- 30225796
TI  - Patient Co-Morbidity and Functional Status Influence the Occurrence of Hospital
      Acquired Conditions More Strongly than Hospital Factors.
AB  - BACKGROUND: Never events (NE) and hospital-acquired conditions (HAC) are used by
      Medicare/Medicaid Services to define hospital performance measures that dictate
      payments/penalties. Pre-op patient comorbidity may significantly influence HAC
      development. METHODS: We studied 8,118,615 patients from the NIS database (2002
      2012) who underwent upper/lower gastrointestinal and/or hepatopancreatobiliary
      procedures. Multivariate analysis, using logistic regression, was used to
      identify HAC and NE risk factors. RESULTS: A total of 63,762 (0.8%) HAC events
      and 1645 (0.02%) NE were reported. A total of 99.9% of NE were retained foreign
      body. Most frequent HAC were: pressure ulcer stage III/IV (36.7%), poor glycemic
      control (26.9%), vascular catheter-associated infection (20.3%), and catheter
      associated urinary tract infection (13.7%). Factors correlating with HAC
      included: open surgical approach (AOR: 1.25, P < 0.01), high-risk patients with
      significant comorbidity [severe loss function pre-op (AOR: 6.65, P < 0.01),
      diabetes with complications (AOR: 2.40, P < 0.01), paraplegia (AOR: 3.14, P <
      0.01), metastatic cancer (AOR: 1.30, P < 0.01), age > 70 (AOR: 1.09, P < 0.01)],
      hospital factors [small vs. large (AOR: 1.07, P < 0.01), non-teaching vs teaching
      (AOR: 1.10, P < 0.01), private profit vs. non-profit/governmental (AOR: 1.20, P <
      0.01)], severe preoperative mortality risk (AOR: 3.48, P < 0.01), and non
      elective admission (AOR: 1.38, P < 0.01). HAC were associated with increased:
      hospitalization length (21 vs 7 days, P < 0.01), hospital charges ($164,803 vs
      $54,858, P < 0.01), and mortality (8 vs 3%, AOR: 1.14, P < 0.01). CONCLUSION: HAC
      incidence was highest among patients with severe comorbid conditions. While
      small, non-teaching, and for-profit hospitals had increased HAC, the strongest
      HAC risks were non-modifiable patient factors (preoperative loss function,
      diabetes, paraplegia, advanced age, etc.). This data questions the validity of
      using HAC as hospital performance measures, since hospitals caring for these
      complex patients would be unduly penalized. CMS should consider patient
      comorbidity as a crucial factor influencing HAC development.

PMID- 30225797
TI  - Characterization of the glucosyltransferase activity of Legionella pneumophila
      effector SetA.
AB  - Legionella pneumophila glucosyltransferase SetA, which is introduced into target
      cells by a type IV secretion system, affects the intracellular traffic of host
      cells. Here, we characterized the enzyme activity of the Legionella effector. We
      report that Asp118 and Arg121 of SetA are essential for glucohydrolase and
      glucotransferase activities. Exchange of Trp36 to alanine reduced the enzyme
      activity of SetA. All three amino acids were crucial for the cytotoxic effects of
      SetA in yeast. We observed that phosphatidylinositol-3-phosphate (PI3P) increased
      the glucosyltransferase activity of SetA severalfold, while the glucohydrolase
      activity was not affected. In the presence of PI3P, we observed the glucosylation
      of actin, vimentin and the chaperonin CCT5 in the cytosolic fraction of target
      cells. Studies on the functional consequences of glucosylation of skeletal muscle
      alpha-actin in vitro revealed inhibition of actin polymerization by
      glucosylation.

PMID- 30225798
TI  - The increase of stage, grading, and metastases in patients undergoing radical
      prostatectomy during the last decade.
AB  - PURPOSE: To investigate changes in clinical data and pathological features of
      prostatectomy specimens of prostate cancer (PCa) patients in a large tertiary
      care center over the last 12 years as potential consequence of reduced acceptance
      of prostate-specific antigen (PSA)-based screening and implementation of active
      surveillance as a therapeutic option in PCa. METHODS: We retrospectively
      identified all patients with PCa who underwent radical prostatectomy at our
      institution between 2004 and 2016 from our clinical database. We reviewed
      clinical and pathological data including patient age, PSA level, number of
      positive cores and Gleason score in prostate biopsy, and pathologic N- and T
      stage, and Gleason score in radical prostatectomy specimen. RESULTS: Data of 5497
      consecutive patients were analyzed. Median PSA increased from 7 (IQR 4.8-10.5) to
      9 ng/ml (IQR 5.8-16.1; p < 0.001), and median number of positive biopsy cores
      increased from 3 (IQR 2-5) to 5 (IQR 3-7; p < 0.001). The proportion of patients
      with Gleason score >= 7 in biopsy and prostatectomy specimens increased from 40
      to 78% and 49 to 89% (p < 0.001), respectively. The rate of locally advanced (>=
      pT3a) and lymph node-positive tumors increased from 28 to 43% and 5 to 16% (p <
      0.001), respectively. CONCLUSIONS: We observed a significant change in clinical
      and pathological findings in our prostatectomy series with a significantly higher
      proportion of aggressive and locally advanced PCa in recent years. These findings
      may be related to a reduced acceptance of PSA-based screening and the use of
      active surveillance as management strategy and have significant impact on daily
      patient care.

PMID- 30225799
TI  - Impaired sleep is associated with low testosterone in US adult males: results
      from the National Health and Nutrition Examination Survey.
AB  - PURPOSE: Testosterone deficiency has been linked to several adverse health
      outcomes and recent data have suggested that abnormal sleep quality may result in
      lower testosterone levels. We assessed the effect of self-reported sleep patterns
      on serum testosterone while controlling for co-morbidities, and baseline
      demographics. MATERIALS AND METHODS: Using data collected from the 2011-2012
      National Health and Nutrition Examination Survey (NHANES), we extracted serum
      total testosterone level, sleep duration, demographic, and co-morbidities for men
      aged 16 years and older. Univariate and multivariate linear regression was used
      to estimate the association of number of hours slept, co-morbidities, and
      demographics with serum testosterone. RESULTS: Among the 9756 individuals in the
      NHANES dataset, 2295 (23.5%) were males 16 years and older with a median
      (interquartile range) age of 46 years (29-62) who also had serum testosterone
      levels drawn. Median serum testosterone level was 377 ng/dL (IQR: 279-492 ng/dL).
      Median number of hours slept was 7 h (IQR: 6-8 h). On multivariate linear
      regression, we found serum testosterone decreased by 0.49 ng/dL per year of age
      (p = 0.04), 5.85 ng/dL per hour loss of sleep (p < 0.01) and 6.18 ng/dL per unit
      of body mass index (BMI) increase (p < 0.01). CONCLUSIONS: Among men aged 16-80
      in the United States, we found increasing age, impaired sleep and elevated BMI is
      associated with low testosterone. It is important, therefore, that evaluation and
      treatment of reduced serum testosterone should also include improving sleep
      duration in combination with weight management.

PMID- 30225800
TI  - Long-term results of ProACT primary and repeat implantation for treatment of
      stress urinary incontinence in men.
AB  - INTRODUCTION: Urinary incontinence in men after radical prostatectomy affects
      strongly quality of life. If conservative treatment fails, surgical treatment
      consists of implantable devices. If the requirement of manual dexterity in the
      artificial sphincter is to be avoided, the ProACT system offers a readjustable
      system, which shows good continence, but also high revision rates. Aim of our
      single-centre, single-surgeon study was to evaluate the success and revision
      rates of ProACT over long-term follow-up and if repeat ProACT implantation after
      failure would be a reasonable strategy. MATERIALS AND METHODS: In May 2017,
      follow-up of all patients who underwent ProACT implantation between 2003 and 2013
      was obtained. Parameters were numbers of pads used, filling volume of balloons,
      and patient-reported satisfaction. Furthermore, revisions were noted. RESULTS:
      Between 2003 and 2013, 134 patients were implanted a ProACT system. Median age
      was 71 years; median follow-up was 118 months. 112 implantations were successful
      (82.6%) and the number of pads used decreased significantly (p < 0.005). 63
      patients were revised and 49 were successful (77.8%). No differences in success
      rate, pads used, or filling volume were seen (all p > 0.8). In a second revision,
      again, no differences in success rate or pads used were noted (all p > 0.7).
      Patients' personal satisfaction was high despite the high revision rate.
      CONCLUSION: In the hands of an experienced surgeon, ProACT is a safe and
      effective therapy for post-prostatectomy incontinence especially if mayor surgery
      is to be avoided. Revision rates are high, but the results of ProACT
      reimplantation are comparable to the results after the first implantation.

PMID- 30225803
TI  - J-shaped curve for cardiovascular mortality: systolic or diastolic blood
      pressure?
AB  - Aggressive reduction of blood pressure (BP) may increase cardiovascular events
      (the J-curve phenomenon) in certain populations. There is a high number of
      available studies of antihypertensive treatment that provide strong evidence for
      J-shaped relationships between both diastolic and systolic BP and main
      cardiovascular outcomes. Nonetheless, most available studies were observational,
      and randomized trials might not have or lost their statistical power in post-hoc
      analysis. Contrariwise, most of prospective trial to demonstrate the benefits of
      intensive blood pressure control were inconclusive. Therefore, further studies
      are still necessary in order to clarify this issue.

PMID- 30225801
TI  - Mapping fine-scale anatomy of gray matter, white matter, and trigeminal-root
      region applying spherical deconvolution to high-resolution 7-T diffusion MRI.
AB  - OBJECTIVES: We assessed the use of high-resolution ultra-high-field diffusion
      magnetic resonance imaging (dMRI) to determine neuronal fiber orientation density
      functions (fODFs) throughout the human brain, including gray matter (GM), white
      matter (WM), and small intertwined structures in the cerebellopontine region.
      MATERIALS AND METHODS: We acquired 7-T whole-brain dMRI data of 23 volunteers
      with 1.4-mm isotropic resolution; fODFs were estimated using constrained
      spherical deconvolution. RESULTS: High-resolution fODFs enabled a detailed view
      of the intravoxel distributions of fiber populations in the whole brain. In the
      brainstem region, the fODF of the extra- and intrapontine parts of the trigeminus
      could be resolved. Intrapontine trigeminal fiber populations were crossed in a
      network-like fashion by fiber populations of the surrounding cerebellopontine
      tracts. In cortical GM, additional evidence was found that in parts of primary
      somatosensory cortex, fODFs seem to be oriented less perpendicular to the
      cortical surface than in GM of motor, premotor, and secondary somatosensory
      cortices. CONCLUSION: With 7-T MRI being introduced into clinical routine, high
      resolution dMRI and derived measures such as fODFs can serve to characterize fine
      scale anatomic structures as a prerequisite to detecting pathologies in GM and
      small or intertwined WM tracts.

PMID- 30225802
TI  - Urine volume as a predicting factor for furosemide clearance during continuous
      infusion in AKI septic shock patients on hemodiafiltration.
AB  - BACKGROUND: This study assessed the contribution of intracorporeal (IC) and
      extracorporeal clearance (EC) of furosemide in patients with septic acute kidney
      injury (AKI), and the relationship between plasma concentrations and urine
      volume. METHODS: Prospective cohort observational study of 15 patients with
      septic AKI undergoing continuous veno-venous hemodiafiltration (CVVHDF) divided
      according to urine volume (< 500 ml/12 h, Oliguria group, n = 5; > 500 ml/12 h,
      Diuresis group, n = 10) during continuous infusion of furosemide (120 mg/12 h) at
      steady-state condition. Plasma and effluent furosemide concentrations were
      determined by high-performance liquid chromatography (HPLC)-mass spectrometry
      every 12 h for 48 h. RESULTS: Furosemide plasma concentrations and total body
      clearance (TBC) were 6.14 mg/l and 22.1 ml/min for the Oliguria group, and 2.63
      mg/l and 54.4 ml/min for the Diuresis group, respectively (p < 0.05). When urine
      volume was < 500 ml/24 h, the furosemide plasma concentrations peaked at the
      potentially toxic value of 13.0 mg/l. Furosemide EC was not relevant for the
      Diuresis group, but it represented 18% of TBC for the Oliguria group. Furosemide
      plasma concentrations correlated positively with dose infusion for both groups (r
      = 0.728 and 0.685, p < 0.05), and negatively with urine volume only for the
      Diuresis (r = - 0.578, p < 0.01) but not for the Oliguria group (r = - 0.089, p =
      0.715). CONCLUSIONS: For patients with urine volume > 500 ml/12 h continuous
      infusion of furosemide up to 480 mg/24 h leads to increasing urine volume, which
      can predict furosemide plasma levels within its safety range. When the urine
      volume is lower, the furosemide plasma levels are increased beyond any further
      diuretic efficacy.

PMID- 30225804
TI  - Rapid screening for cognitive deficits in attention deficit and hyperactivity
      disorders with the screen for cognitive impairment in psychiatry.
AB  - Cognitive impairments constitute a core feature of attention deficit and
      hyperactivity disorders (ADHD), but are infrequently assessed in the clinical
      setting. We have previously demonstrated the ability of an objective cognitive
      battery, the Screen for Cognitive Impairment in Psychiatry (SCIP), to
      differentiate adult ADHD patients from healthy controls in five cognitive
      domains. Here, we further characterize these subtle cognitive deficits by
      conducting additional univariate analyses on our ADHD dataset to assess the
      contributions of various demographic characteristics on SCIP performance and to
      determine correlations between SCIP scores and scores on other measures
      evaluating illness severity, perceived cognitive deficits, and overall
      functioning. Age and years of education were moderately associated with
      performance on the SCIP and/or its subscales in our ADHD cohort. The SCIP global
      index score was moderately correlated with clinician-rated measures of illness
      severity and weakly associated with clinician-rated overall functional status.
      Intriguingly, overall SCIP performance was only weakly associated with patient
      self-reported measures of cognitive functioning. Of practical importance, small
      to-moderate associations were consistently observed between performances on two
      subscales of the SCIP and the other measures evaluating illness severity, overall
      functioning, and patient self-reported cognitive functioning (the working memory
      and visuomotor tracking subscales). Thus, these data demonstrate that the SCIP,
      particularly the working memory and visuomotor tracking subscales, is sensitive
      enough to detect cognitive deficits in adult patients with ADHD, and that these
      deficits are correlated with functional impairments. Furthermore, these data
      highlight the importance of integrating both objective and subjective evaluations
      of cognition in adult ADHD.

PMID- 30225805
TI  - The impact of successful learning of self-regulation on reward processing in
      children with ADHD using fMRI.
AB  - Neurofeedback (NF) is a non-pharmacological treatment for attention
      deficit/hyperactivity disorder (ADHD) that is targeting self-regulation, is
      efficacious when standard protocols are used and induces partly specific
      neurophysiological changes in the inhibitory network. However, its effects on
      reward processing, which is also considered an important aspect of ADHD and has
      been linked to neurophysiological deficits, remain unknown. Children with ADHD (N
      = 15, mean age 11.8, SD 1.52) were randomly assigned to either slow cortical
      potential NF (n = 8) or EMG biofeedback control training (n = 7) and received 20
      sessions of training under comparable conditions. Learning was defined as the
      slope of successful training runs across all transfer sessions. Whole brain
      analysis, region-of-interest analysis of anticipatory ventral striatal (VS)
      activation, and analysis of behavioral data were performed. Clinically, the NF
      group improved more than the EMG group. Whole brain analysis indicated increased
      activation in the left superior frontal gyrus in the control group only, and in
      medial prefrontal cortex and dorsolateral prefrontal gyrus (DLPFC) after
      treatment across all groups. Only successful learners of self-regulation (n = 8)
      showed increased left inferior frontal gyrus and DLPFC activation after
      treatment. Left VS activation was increased after treatment and showed a
      significant time*medication-status interaction. Specific treatment effects were
      found in left frontal regions for the control treatment and successful learners.
      Also, unmedicated participants, irrespective of treatment type or successful
      learning, showed treatment-induced improvement in reward processing. The results
      suggest no prominent specific effect of NF on reward processing. However,
      cautious interpretation is warranted due to the small sample.

PMID- 30225806
TI  - Searching images and the meaning of alarm calls.
AB  - The snake alarm call of Japanese tits prompts nesting adults to search for and
      mob the reptile until it is driven away. From playback experiments, Suzuki (2018)
      has inferred that the call provides an associative cue, evoking a searching image
      of the salient visual features of the predator-a novel approach to exploring
      visual attention and vocal communication in the wild.

PMID- 30225807
TI  - Novel flexibility of social learning in dog puppies.
AB  - Social learning has a large impact on fitness by reducing the costs and dangers
      associated with independent learning but little research has been conducted to
      investigate the ontogeny or individual development of this type of learning.
      Recent research indicated that puppies demonstrate social learning to both
      conspecific and human demonstrators, but were also more likely to learn better
      from an unfamiliar conspecific compared to their mother.

PMID- 30225808
TI  - Minimally invasive aortic valve replacement through a right anterolateral mini
      thoracotomy for the treatment of octogenarians with aortic valve stenosis.
AB  - Because of concerns about the high risk of perioperative complications, the
      feasibility of minimally invasive aortic valve replacement (MIAVR) for elderly
      patients remains controversial. Here, we review our results of MIAVR in
      octogenarians with aortic valve stenosis (AS). Between October 2012 and December
      2017, 110 patients with AS underwent MIAVR via a right anterolateral mini
      thoracotomy; 41 patients were octogenarian (Group O). The perioperative outcomes
      of these patients were compared with those of the 69 patients who were less than
      80 years of age (Group Y). A preoperative contrast-enhanced computed tomography
      (CT) scan was performed in all patients to guide the patient selection and aid
      the decision regarding cannulation sites. Among all cases of isolated aortic
      valve replacement, MIAVR accounted for 47% cases during this study period. The
      mean age of Group O was 83.6 +/- 2.9 years, with a maximum age of 89. In Group O,
      there were no in-hospital deaths or morbidity, including stroke. The rate of
      blood transfusion was significantly higher in Group O than in Group Y (P = 0.01).
      However, there was no significant difference in ventilation time, the length of
      intensive care unit stay, the length of hospital stay, or in the rates of
      cumulative survival and freedom from valve-related complications. With careful
      patient selection and a perfusion strategy based on preoperative CT scan,
      equivalent outcomes of MIAVR were even achieved in octogenarians.

PMID- 30225809
TI  - Pulmonary arterial compliance is a useful predictor of pulmonary vascular disease
      in congenital heart disease.
AB  - Histopathological assessment of the pulmonary arteries is crucial to determine
      the surgical indications in patients with congenital heart disease (CHD) and
      intractable pulmonary vascular disease (PVD). We aimed to clarify whether
      pulmonary hemodynamic parameters can predict PVD in patients with CHD and
      pulmonary arterial hypertension (PAH) We performed histopathological evaluations
      of lung specimens and cardiac catheterizations in 27 patients with CHD-PAH. We
      divided these patients into the patients with and without PVD, and compared
      pulmonary hemodynamic parameters including pulmonary arterial compliance (Cp)
      between two groups. Age at lung biopsy was 4 (2-7) months. There were 16 patients
      with trisomy 21. Cardiac diagnosis included ventricular septal defect in 16,
      atrial septal defect in 5, atrioventricular septal defect in 4, and others in 2.
      There were 11 patients with histopathologically proven PVD (Heath-Edwards
      classification grade >= 3 in 5; the index of PVD >= 1.1 in 3; extremely thickened
      media in 6; hypoplasia of the pulmonary arteries in 3). Cp in the patients with
      PVD was significantly lower than that in patients without PVD (0.99 [0.74-1.42]
      vs 1.56 [1.45-1.88], p = 0.0047), although there was no significant difference in
      the ratio of systemic to pulmonary blood flow, pulmonary arterial pressure, and
      resistance between two groups. A Cp cutoff value of < 1.22 ml/mmHg m2 as a
      predictor of PVD yielded a sensitivity and a specificity of 93% and 64%,
      respectively. Pulmonary arterial compliance can be a predictor of PVD among
      patients with CHD-PAH.

PMID- 30225810
TI  - Impact of aneurysm shape on morbidity after clipping of unruptured intracranial
      aneurysms.
AB  - BACKGROUND: Complex aneurysm shape is a predominant risk factor for aneurysm
      rupture but its impact on clinical outcome after clipping remains unclear. The
      objective of the present study was to compare complications and morbidity after
      clipping of unruptured single-sac aneurysms (SSAs) and aneurysms with multiple
      sacs (MSAs). METHODS: A retrospective, single-center study was conducted for
      patients that were treated between 2010 and 2018. We analyzed surgical
      parameters, treatment-related complications, and morbidity, defined as any
      increase in the modified Rankin scale at 3-month follow-up. RESULTS: We
      identified 101 patients (mean age: 52.9 +/- 10.5 years) that underwent clipping
      for 57 SSAs and 44 MSAs. The two groups were comparable regarding aneurysm size
      and neck width. Clipping of MSAs was associated with a longer operation time (p =
      0.008) and increased use of intraoperative indocyanine green (p = 0.016) than
      SSAs. Complications occurred more often in the MSA group (29.5%) than in the SSA
      group (14.0%; p = 0.057). Morbidity was significantly higher in the MSA group
      (20.5%) than in the SSA group (3.5%, p = 0.009). In the univariate analysis, the
      odds of morbidity were 7.1 times greater for MSAs than for SSAs (95% CI 1.4
      34.7). CONCLUSIONS: Morbidity after microsurgical clipping is significantly
      increased in MSAs as compared to SSAs. This may be attributed to a more difficult
      clip placement with stronger manipulation of the aneurysm dome and the
      surrounding brain tissue.

PMID- 30225811
TI  - Multidisciplinary approach in the treatment of spinal dural arteriovenous fistula
      results of endovascular and surgical treatment.
AB  - BACKGROUND: The results of treatment for spinal dural arteriovenous fistula
      (SDAVF) have been controversial. The goal of this study was to compare results of
      endovascular and surgical treatments to contribute to determining an optimal
      treatment strategy. METHODS: A retrospective analysis of the set of 24 SDAVF
      patients (11 in the endovascular and 13 in the surgical group) was performed. The
      clinical effect (using the modified Rankin scale [mRS]), the radicality, and the
      number of clinical recurrences as well as the impact of age, the level of
      impairment, and the duration of symptoms before the treatment were evaluated.
      RESULTS: The average age was 60.1 +/- 8.4 years. The median duration of symptoms
      before establishing a diagnosis was 12 (1-70) months. Clinical improvement was
      reported in 11 out of 24 (45.8%) patients (36.4% following embolization and 53.8%
      following surgery, p = 0.444). Radical performance was achieved in 47.4% of
      endovascular versus 92.9% of surgical procedures (p = 0.009). Clinical recurrence
      was reported in 35.3% of patients in the endovascular group, whereas no clinical
      recurrence was reported in the surgical group (p = 0.0133). The graphical
      residuum after 1 surgery out of 14 (7.1%) was cured early during the control
      angiography. Clinical improvement was reported 42.1% of patients with mRS <= 3
      versus 60% of patients with mRS >= 4 and, in 57.1% of patients aged >= 60 versus
      in 30% of patients < 60 years (p > 0.05 in both cases). The impact of the
      duration of symptoms on the clinical results was not statistically significant.
      CONCLUSIONS: The surgical treatment of SDAVF appeared to be a more efficient
      method in terms of the clinical effect, radicality, and lower recurrence rate in
      comparison with the endovascular treatment. No statistically significant
      dependence of the clinical result on age, deficit burden, or symptom duration was
      found.

PMID- 30225812
TI  - Distinct UV-A or UV-B irradiation induces protochlorophyllide photoreduction and
      bleaching in dark-grown pea (Pisum sativum L.) epicotyls.
AB  - The effects of distinct UV-A and UV-B radiations were studied on etiolated pea
      (Pisum sativum L.) epicotyls. Emission spectra of the native protochlorophyll and
      protochlorophyllide forms were measured when epicotyls were excited with 360 or
      300 nm light. The UV-A (360 nm) excited mainly the non-enzyme-bound monomers of
      protochlorophyll and protochlorophyllide and the UV-B (300 nm) excited
      preferentially the flash-photoactive protochlorophyllide complexes. These latter
      complexes converted into short- and long-wavelength chlorophyllide forms at 10-s
      illumination with both wavelength irradiations. As the spectral changes were very
      small, the effects of longer illumination periods were studied. Room temperature
      fluorescence emission spectra were measured from the same epicotyl spots before
      and after irradiation with various wavelengths between 280 and 360 nm for 15 min
      and the "illuminated" minus "dark" difference spectra were calculated. Both the
      UV-A and the UV-B irradiations caused photoreduction of protochlorophyllide into
      chlorophyllide. At 10 umol photons m-2 s-1, the photoreduction rates were
      similar, however, at 60 umol photons m-2 s-1, the UV-B irradiation was more
      effective in inducing chlorophyllide formation than the UV-A. The action spectra
      of protochlorophyllide plus protochlorophyll loss and chlorophyllide production
      showed that the radiation around 290 nm was the most effective in provoking
      protochlorophyllide photoreduction and the UV light above 320 nm caused strong
      bleaching. These results show that the effect of the UV radiation should be
      considered when discussing the protochlorophyllide-chlorophyllide photoreduction
      during germination and as a part of the regeneration of the photosynthetic
      apparatus proceeding in the daily run of photosynthesis.

PMID- 30225813
TI  - Lectin-binding and dissociation/reconstitution studies on the trichocysts of the
      dinoflagellate Oxyrrhis marina.
AB  - Trichocyst-enriched fractions were isolated from the dinoflagellate Oxyrrhis
      marina and subjected to protein staining and lectin-binding studies, to
      dissociation experiments using heat, and to solubilization/reconstitution
      experiments using 6 M guanidine hydrochloride. The trichocysts could be stained
      by Alcian Blue and became labeled by the lectin Concanavalin A, but not by wheat
      germ agglutinin. The trichocysts did not dissociate when the fractions were
      heated for 5 min at 40 or 50  degrees C. Heating at 60  degrees C resulted in the
      dissociation of trichocysts into irregular filamentous structures. These
      filaments were still present when the fractions were incubated for 5 min at
      temperatures of 70 and 80  degrees C. Reassembly was not achieved by subsequent
      cooling steps. The disintegration of trichocysts was also achieved in 6 M
      guanidine hydrochloride, and reassembly into filamentous structures, similar to
      those obtained by heat, occurred after dialysis against distilled water. Electron
      microscopy revealed that the filaments created either by heat or using guanidine
      hydrochloride by far did not resemble native trichocysts. They were much thinner
      (5-7 nm in width), missed the characteristic striation of electron-dense and 
      transparent lines along the longitudinal axes, and showed much more bending.
      Furthermore, they tend to merge to thicker shapeless structures and blob-like
      aggregates. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed
      that fractions enriched either in trichocysts or in reconstituted filamentous
      structures obtained in the guanidine hydrochloride solubilization experiments
      were dominated by proteins with relative molecular weights in the range of
      approximately 15 to 29 kDa. Minor amounts of larger proteins were also detected.
      Tryptic in gel digestion followed by mass spectrometry confirmed the presence of
      almost the same set of proteins within the both, the trichocyst-enriched
      fractions, and the fractions of filaments reconstituted thereafter. These
      proteins were previously proposed to represent the matrix polypeptides of the
      trichocysts of Oxyrrhis marina (Rhiel et al., Protoplasma 255: 217-230, 2018).

PMID- 30225815
TI  - Optimizing cardiac sarcoid imaging with FDG PET: Lessons from studies of
      physiologic regulation of myocardial fuel substrate utilization.

PMID- 30225814
TI  - Performance of closed-loop resuscitation of haemorrhagic shock with fluid alone
      or in combination with norepinephrine: an experimental study.
AB  - BACKGROUND: Closed-loop resuscitation can improve personalization of care,
      decrease workload and bring expert knowledge in isolated areas. We have developed
      a new device to control the administration of fluid or simultaneous co
      administration of fluid and norepinephrine using arterial pressure. METHOD: We
      evaluated the performance of our prototype in a rodent model of haemorrhagic
      shock. After haemorrhagic shock, rats were randomized to five experimental
      groups: three were resuscitated with fluid and two with co-administration of
      fluid and norepinephrine. Among groups resuscitated with fluid, one was
      resuscitated by a physician and two were resuscitated according to two different
      closed-loop algorithms. Among groups resuscitated with fluid and norepinephrine,
      one was resuscitated by a physician and the other one by the closed-loop device.
      The precision of arterial pressure during the resuscitation period was assessed
      using rising time, time passed in the target area and performance error
      calculations. RESULTS: Groups resuscitated with fluid had similar performances
      and passed as much time in the target area of 80-90 mmHg as the manual group
      [manual: 76.8% (67.9-78.2), closed-loop: 64.6% (45.7-72.9) and 80.9% (59.1
      85.3)]. Rats resuscitated with fluid and norepinephrine using closed-loop passed
      similar time in target area than manual group [closed-loop: 74.4% (58.4-84.5) vs.
      manual: 60.1% (46.1-72.4)] but had shorter rising time to reach target area [160
      s (106-187) vs. 434 s (254-1081)] than those resuscitated by a physician. Rats
      resuscitated with co-administration of fluid and norepinephrine required less
      fluid and had less hemodilution than rats resuscitated with fluid alone. Lactate
      decrease was similar between groups resuscitated with fluid alone and fluid with
      norepinephrine. CONCLUSIONS: This study assessed extensively the performances of
      several algorithms for closed-loop resuscitation of haemorrhagic shock with fluid
      alone and with co-administration of fluid and norepinephrine. The performance of
      the closed-loop algorithms tested was similar to physician-guided treatment with
      considerable saving of work for the caregiver. Arterial pressure closed-loop
      guided algorithms can be extended to combined administration of fluid and
      norepinephrine.

PMID- 30225816
TI  - Staged testing as a solution to the challenges of testing lower risk patients.

PMID- 30225817
TI  - HIV treatment outcomes among formerly incarcerated transitions clinic patients in
      a high prevalence setting.
AB  - BACKGROUND: Incarceration disproportionately affects people living with HIV/AIDS.
      When people are released from jail or prison, they face multiple barriers to HIV
      care, and those who do engage in care may have suboptimal HIV treatment outcomes.
      A limited number of studies have investigated HIV treatment outcomes among people
      who have been released from incarceration. METHODS: We conducted a retrospective
      cohort study comparing HIV viral load (VL) suppression and retention in care 12
      months after entry into care among patients of a post-incarceration Transitions
      Clinic (TC) and a comparison group who received HIV care in the same community.
      Of 138 participants, 38 TC patients were matched to 100 non-TC controls based on
      age, race/ethnicity, gender, and date of HIV care entry. RESULTS: There was no
      significant difference in clinical study outcomes between TC and non-TC patients:
      63% vs. 67% (p = 0.67) were retained in care and 54% vs. 63% (p = 0.33) had
      suppressed VL at 12 months. After adjusting for substance use disorder and viral
      load suppression at the start of treatment, the odds ratio of TC patients' 12
      month retention was 0.60 (95% CI 0.25-1.49) and VL suppression was 0.44 (95% CI
      0.16-1.23) compared with non-TC patients. CONCLUSIONS: Our findings show HIV care
      outcomes for patients at a post-incarceration Transitions Clinic that are similar
      to those of community-based comparison patients. The transitions clinic model,
      which provides medical, behavioral health, and supportive services to formerly
      incarcerated people, may be an effective model of care for this population;
      however, more scholarship is needed to quantify the components most effective in
      supporting retention in care and viral load suppression.

PMID- 30225818
TI  - Unusual microbiological presentations in polymicrobial post-operative
      endophthalmitis and their clinical correlations.
AB  - PURPOSE: To report the clinical course, microbiological spectrum and visual
      outcomes of three cases of post-operative endophthalmitis caused by unusual
      combination of micro-organisms. METHODS: Retrospective review of medical charts
      at a tertiary eye care centre over a period of 1 year, of subjects with post
      operative endophthalmitis and more than one microbiological isolate. RESULTS: We
      report 3 cases with unusual combination of microorganisms. In case 1, two
      organisms (Burkholderia cepacia and Aeromonas veronii, from the vitreous cavity
      and capsular bag, respectively) with an identical antibiotic sensitivity pattern
      were found, while in case 2, the organisms (Streptococcus pneumoniae and
      Sphingomonas paucimobilis, from cornea and vitreous cavity, respectively)
      isolated had different sensitivity patterns. In case 3, two different strains of
      the same organism (Enterococcus faecalis) were found. Cases 1 and 2 achieved good
      anatomical and visual outcomes, while in case 3, vision remained poor despite a
      good anatomical outcome. CONCLUSION: Unusual combinations of organisms in post
      operative endophthalmitis can introduce unique clinical characteristics and
      should specifically be considered in atypical clinical presentations, poor
      response to standard therapy and unusual recurrence patterns.

PMID- 30225819
TI  - Magnetic-activated cell sorting is not completely effective at reducing sperm DNA
      fragmentation.
AB  - PURPOSE: To determine whether there is a homogeneous reduction of sperm DNA
      fragmentation (SDF) in sperm samples recovered from the MACS procedure, compared
      to spermatozoa in the initial ejaculate (NEAT) and those retained in the column.
      METHODS: This study investigated the relative change in sperm DNA quality (SDF)
      of neat ejaculates (10 idiopathic infertile and 10 normozoospermic patients) to
      subpopulations of spermatozoa that had passed through the column (MACS-) and
      those retained (MACS+) by the annexin-V conjugated microbeads. RESULTS: While the
      MACS protocol was capable of reducing the mean proportion of SDF (59.2%; P =
      0.000) and sperm with highly degraded DNA (SDD; 65.7%, P = 0.000) in all
      patients, the reduction was not homogeneous across the patient cohort. A
      significant positive correlation (r = 0.772, P = 0.000) was apparent between the
      level of SDF in the NEAT ejaculate and the efficacy of SDF reduction observed in
      the MACS- fraction. CONCLUSION: MACS is capable of reducing the proportion of
      SDF, especially spermatozoa with a highly degraded DNA molecule. However, this
      reduction did not preclude the presence of a small subpopulation of spermatozoa
      with damaged DNA in the MACS- fraction. The MACS protocol was two- to threefold
      more efficient when the SDF in NEAT ejaculate was equal to or greater than 30%.
      In 4 of 20 individuals, the level of SDF after MACS resulted in semen for ICSI
      with a higher or non-significant reduction when compared to SDF observed in the
      NEAT ejaculate.

PMID- 30225820
TI  - IL-1beta predicts IVF outcome: a prospective study.
AB  - PURPOSE: Retrospective cohort studies have shown a relationship between maternal
      serum interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1Ra)
      levels and in vitro fertilization (IVF) cycle outcome. The objective of this
      investigation was to explore the correlation between serum IL-1beta and/or IL-1Ra
      levels obtained prospectively and IVF outcomes. METHODS: Sera from 205 women were
      collected just prior to initiation of their IVF cycle, at the time of human
      chorionic gonadotropin administration, day 24 of IVF cycle, day 28, and day 35.
      Sera were analyzed for IL-1beta and IL-1Ra using commercially available ELISA
      kits. Cycle outcomes were followed prospectively. Data were analyzed using
      Friedman analysis of variance by ranks and chi-square analysis. RESULTS: Among
      women with a viable pregnancy, IL-1beta serum levels increased over time for
      those that proceeded to deliver or had an ongoing pregnancy. There was no
      increase in serum levels for those with subsequent pregnancy loss. Of the women
      that had an embryo transfer, detectable IL-1beta levels at the start of the cycle
      were associated with successful IVF outcome (p = 0.027). Of women with a positive
      pregnancy test, undetectable IL-1beta at the start of the cycle were associated
      with subsequent pregnancy loss (p = 0.046). For all IL1-Ra serum analysis, there
      were no significant results. CONCLUSIONS: The increasing levels of IL-1beta over
      time are consistent with the known role of the IL-1 cytokine family in
      implantation and pregnancy. Additionally, we confirm in a prospective
      investigation the positive relationship between detectable serum IL-1beta at the
      start of IVF cycle and outcome.

PMID- 30225822
TI  - Response to Lewis A: Reconciling the Case of Jahi Mcmath.

PMID- 30225821
TI  - Static Magnetic Field (SMF) as a Regulator of Stem Cell Fate - New Perspectives
      in Regenerative Medicine Arising from an Underestimated Tool.
AB  - Tissue engineering and stem cell-based therapies are one of the most rapidly
      developing fields in medical sciences. Therefore, much attention has been paid to
      the development of new drug-delivery systems characterized by low cytotoxicity,
      high efficiency and controlled release. One of the possible strategies to achieve
      these goals is the application of magnetic field and/or magnetic nanoparticles,
      which have been shown to exert a wide range of effects on cellular metabolism.
      Static magnetic field (SMF) has been commonly used in medicine as a tool to
      increase wound healing, bone regeneration and as a component of magnetic
      resonance technique. However, recent data shed light on deeper mechanism of SMF
      action on physiological properties of different cell populations, including stem
      cells. In the present review, we focused on SMF effects on stem cell biology and
      its possible application as a tool for controlled drug delivery. We also
      highlighted the perspectives, in which SMF can be used in future therapies in
      tissue engineering due to its easy application and a wide range of possible
      effects on cells and organisms.

PMID- 30225823
TI  - Re-evaluating the Weekend Effect on SAH: A Nationwide Analysis of the Association
      Between Mortality and Weekend Admission.
AB  - OBJECTIVE: Multiple studies have shown worse outcomes in patients admitted for
      medical and surgical conditions on the weekend. However, past literature
      analyzing this "weekend effect" on subarachnoid hemorrhage (SAH) found no
      significant increase in mortality. This study utilizes more recent data to re
      evaluate the association between weekend admission and mortality of patients
      hospitalized for SAH. METHODS: This retrospective cohort study queried the SAH
      patients in the Nationwide Inpatient Sample (NIS) database who were discharged
      from 2006 through 2014 during the weekend. RESULTS: Of the 54,703 admissions for
      SAH identified during the study period, 14,821 (27.1%) occurred over the weekend.
      Patients admitted over the weekend had a mean age of 59.2 years and were most
      likely to be female (59.6%), to be white (62.9%), located in the south region of
      the USA (40.1%), and be admitted to a teaching hospital (74.4%). When compared
      directly to weekday admissions, patients admitted over the weekend had higher
      odds of in-hospital mortality (odds ratio 1.07; confidence interval 95%, 1.02
      1.12). There was no significant difference shown in the rate patients get
      surgical clipping versus endovascular coiling (p = 0.28) or the amount of time
      between admission to procedure for clipping (p = 0.473) or coiling (p = 0.255) on
      the weekend versus a weekday. CONCLUSION: Based on our findings, the likelihood
      of the in-hospital mortality was higher for patients admitted over the weekend.
      However, the characteristics of the study, primarily observational, prevent us
      arriving at an accurate conclusion about why this occurs; hence, we believe it is
      an important starting point to consider for future research.

PMID- 30225824
TI  - Limitations in and Solutions for Improving the Functionality of Picture Archiving
      and Communication System: an Exploratory Study of PACS Professionals'
      Perspectives.
AB  - Picture Archiving and Communication System (PACS) technology is evolving leading
      to improvements in the PACS functionality. However, the needs and expectations of
      PACS users are increasing to cope with the rising demands for improving the
      workflow and enhancing efficiency in healthcare. The aim was to study the
      limitations in the current generation of PACS and solutions for improving PACS
      functionality. This was a longitudinal online observational study of the
      perspectives of PACS professionals accessed through four online discussion groups
      on PACS using the LinkedIn network. In this exploratory study, the methodology
      involved a thematic analysis of qualitative data comprising 250 online
      posts/comments made by 124 unique PACS professionals collected between January
      2014 and December 2015. Participants were mostly male (n = 119, 96%) from the
      North America (n = 88, 71%). Key themes on limitations in the current generation
      of PACS were image transmission problems, network and hardware issues,
      difficulties in changing specific settings, issues in hardcoded Digital Imaging
      and Communication in Medicine attributes, and problems in implementing open
      source PACS. Main themes on solutions for improving PACS functionality were the
      integration of multisite PACS, multimedia for PACS, web-based PACS, medical image
      viewer, open source PACS, PACS on mobile phones, vendor neutral archives for
      PACS, speech recognition and integration in PACS, PACS backup and recovery, and
      connecting PACS with other hospital systems. Despite ongoing technological
      developments, the current generation of PACS has limitations that affect PACS
      functionality leading to unmet needs and requirements of PACS users, which could
      impact workflow and efficiency in healthcare.

PMID- 30225825
TI  - The prevalence of underweight and overweight/obesity and its correlates among
      adults in Laos: a cross-sectional national population-based survey, 2013.
AB  - PURPOSE: The study aimed to assess the prevalence of underweight and overweight
      or obesity and their sociodemographic, lifestyle, and health factors in a
      national adult population in Lao People's Democratic Republic (PDR) (Laos).
      METHODS: A national cross-sectional study based on a stratified cluster random
      sampling was conducted in 2013. The total sample included 2531 individuals 18-64
      years, (females = 59.3%; mean age 38.7 years, SD = 12.8) from Laos. Questionnaire
      interview, blood pressure and anthropometric measurements, and biochemistry tests
      were conducted. Multinomial logistic regression was utilized to determine the
      association between sociodemographic, lifestyle and health status factors, and
      underweight and overweight or obesity relative to normal weight. RESULTS: Using
      Asian criteria for body mass index (BMI) classification, 9.7% of the population
      was underweight (BMI < 18.5, kg/m2), 47.5% had normal weight (BMI 18.5-22.9
      kg/m2), 17.5% overweight (23.0-24.9 kg/m2), 19.6% class I obesity (BMI 25.0-29.9
      kg/m2), and 5.6% class II obesity (BMI >= 30.0 kg/m2) (or 42.8% overweight, class
      I or class II obesity). In adjusted multinomial logistic regression, female sex
      (adjusted relative risk ratio-ARRR 0.67, confidence interval-CI 0.45, 0.99),
      current tobacco use (ARRR 1.57, CI 1.02, 2.41), and having no hypertension (ARRR
      0.50, CI 0.26, 0.97) were associated with underweight, and middle and older age
      (ARRR 1.79, CI 1.41, 2.25), being Lao-Tai (ARRR 1.37, CI 1.06, 1.76), urban
      residence (ARRR 1.62, CI 1.20, 2.17), having meals outside home (ARRR 1.36, CI
      1.04, 1.77), no current tobacco use (ARRR 0.57, CI 0.34, 0.59), low physical
      activity (ARRR 1.39, CI 1.01, 1.92), having hypertension (ARRR 2.52, CI 1.94,
      3.26), and dyslipidaemia (ARRR 1.56, CI 1.21, 2.00) were associated with
      overweight or obesity. CONCLUSION: A dual burden of both adult underweight and
      overweight or obesity was found in Laos. Sociodemographic, lifestyle, and health
      status risk factors were identified for underweight and overweight or obesity,
      which can help in guiding public health programmes to address both these
      conditions. LEVEL OF EVIDENCE: Level V, descriptive cross-sectional survey.

PMID- 30225826
TI  - Preclinical markers of atherosclerosis in acromegaly: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: Multiple studies investigated preclinical markers of peripheral
      vascular damage in acromegaly (ACRO) reporting discordant results. The aim of
      this study was to run a meta-analysis to examine whether intima media thickness
      (IMT), flow mediated dilation (FMD) and arterial pulse wave velocity (PWV) are
      affected in acromegalic patients and to assess the impact of effective treatment
      of growth hormone excess on these outcomes. STUDY SELECTION: Twenty-seven studies
      comparing ACRO vs control (CON) populations and active (ACT) vs inactive (INACT)
      ACRO were included in the meta-analysis. DATA SYNTHESIS: ACRO compared to CON
      have higher IMT (ES = 0.83, 95% C.I. 0.35-1.30), p = 0.001, impaired FMD (ES = -
      1.59, 95% C.I. - 2.33 to - 0.85, p < 0.0001) and higher PWV (ES = 0.76 95% C.I.
      0.37-1.16, p = 0.0001). When patients with ACT vs INACT disease were considered
      IMT was higher (ES = 0.43, 95% C.I. 0.02-0.84, p = 0.041) and FMD was impaired
      (ES = - 0.66, 95% C.I. - 1.28 to 0.04, p = 0.038) in ACT patients. Meta
      regression analysis of studies comparing IMT in ACT vs INACT acromegalic patients
      showed a significant and inverse association between the effect size and the
      percent of hypertensive (p = 0.025) and diabetic (p = 0.041) patients.
      CONCLUSIONS: IMT, FMD and arterial stiffness are impaired in acromegaly showing
      that these patients may be at increased risk of atherosclerosis. In patients with
      active disease these preclinical markers of atherosclerosis are worse compared to
      patients with inactive disease but the role of diabetes and hypertension is
      prevailing on growth hormone excess.

PMID- 30225827
TI  - Correction to: Effects of a combined exercise plus diet program on
      cardiorespiratory fitness of breast cancer patients.
AB  - In the original publication of this article, Table 1 was published incorrectly.
      The correct Table 1 is given in the following page.

PMID- 30225830
TI  - Whole mouse brain structural connectomics using magnetic resonance histology.
AB  - Diffusion tensor histology holds great promise for quantitative characterization
      of structural connectivity in mouse models of neurological and psychiatric
      conditions. There has been extensive study in both the clinical and preclinical
      domains on the complex tradeoffs between the spatial resolution, the number of
      samples in diffusion q-space, scan time, and the reliability of the resultant
      data. We describe here a method for accelerating the acquisition of diffusion MRI
      data to support quantitative connectivity measurements in the whole mouse brain
      using compressed sensing (CS). The use of CS allows substantial increase in
      spatial resolution and/or reduction in scan time. Compared to the fully sampled
      results at the same scan time, the subtle anatomical details of the brain, such
      as cortical layers, dentate gyrus, and cerebellum, were better visualized using
      CS due to the higher spatial resolution. Compared to the fully sampled results at
      the same spatial resolution, the scalar diffusion metrics, including fractional
      anisotropy (FA) and mean diffusivity (MD), showed consistently low error across
      the whole brain (< 6.0%) even with 8.0 times acceleration. The node properties of
      connectivity (strength, cluster coefficient, eigenvector centrality, and local
      efficiency) demonstrated correlation of better than 95.0% between accelerated and
      fully sampled connectomes. The acceleration will enable routine application of
      this technology to a wide range of mouse models of neurologic diseases.

PMID- 30225832
TI  - Tumor Cell Content and RNA Integrity of Surgical Tissues from Different Types of
      Tumors and Its Correlation with Ex Vivo and In Vivo Ischemia.
AB  - BACKGROUND: Tissues from tumor patients are important resources for promoting
      cancer research, and therefore many biobanks have been established to collect
      tumor tissues; however, the quality of tumor tissues after surgical resection has
      not been well documented. METHODS: A total of 896 cases of tissues from 12 types
      of tumors were chosen for this study. First, histopathological examination was
      conducted to evaluate the tumor cell content; second, microchip electrophoresis
      was used to determine the RNA integrity number (RIN) in 466 cases of tissues with
      a tumor cell content >= 75%; and, finally, a correlation test was used to analyze
      the effect of ischemia on RNA integrity in 384 cases of tissues with a recorded
      ischemia time. RESULTS: Tumor tissues from 12 different organs had different
      tumor cell contents and RNA integrity. The liver had the highest percentage
      (69.7%) of tissue samples with a tumor cell content >= 75%, and the highest
      percentage (96%) of samples with an RIN >= 7. RNA integrity was not correlated
      with limited ex vivo ischemia time (5-60 min) in any of the 12 types of tumors.
      In contrast, a significant correlation with in vivo ischemia time was observed in
      several types of tumors. CONCLUSIONS: Not every sample of excised tumor tissue
      has a sufficient amount of tumor cells and enough RNA integrity. In vivo ischemia
      has a more significant influence on RNA integrity, and tumor tissues have
      different tolerances to pre-analytical variables. Those conducting translational
      research should pay attention to pre-analytical variables when collecting and
      utilizing tumor tissues.

PMID- 30225833
TI  - Oncological Outcomes of Nipple-Sparing Mastectomy: A Single-Center Experience of
      1989 Patients.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly used in women with
      breast cancer who are not eligible for conservative surgery, but extensive
      outcome data are lacking and indications have not been established. OBJECTIVE:
      The aim of this study was to assess the oncological outcomes of NSM in a large
      series of patients with invasive or in situ breast cancer treated at a single
      center. METHODS: We analyzed 1989 consecutive women who had an NSM in 2003-2011,
      for invasive (1711 patients) or in situ cancer (278 patients) at the European
      Institute of Oncology, Italy, and followed-up to December 2016. Endpoints were
      local recurrences, recurrences in the nipple-areola complex (NAC), NAC necrosis,
      and overall survival (OS). RESULTS: After a median follow-up of 94 months
      (interquartile range 70-117), 91/1711 (5.3%) patients with invasive cancer had
      local recurrence (4.8% invasive disease, 0.5% in situ disease), and 11/278 (4.0%)
      patients with in situ disease had local recurrence (1.8% invasive disease, 2.2%
      in situ disease). Thirty-six (1.8%) patients had NAC recurrence, 9 with in situ
      disease (4 invasive and 5 in situ recurrences), and 27 with invasive disease (18
      invasive and 9 in situ recurrences). NAC loss for necrosis occurred in 66 (3.3%)
      patients. There were 131 (6.6%) deaths, 109 (5.5%) as a result of breast cancer.
      OS at 5 years was 96.1% in women with invasive cancer and 99.2% in women with in
      situ disease. CONCLUSIONS: The findings in this large series, with a median
      follow-up of nearly 8 years, indicate that NSM is oncologically safe for selected
      patients. The rate of NAC loss was acceptably low.

PMID- 30225834
TI  - Changes in the Evaluation and Management of Adrenocortical Carcinoma.

PMID- 30225831
TI  - Genetic Basis of Delayed Hypersensitivity Reactions to Drugs in Jewish and Arab
      Populations.
AB  - Genetic variation can affect drug pharmacokinetics and pharmacodynamics and
      contribute to variability between individuals in response to medications.
      Specifically, differences in allele frequencies among individuals and ethnic
      groups have been associated with variation in their propensity to develop drug
      hypersensitivity reactions (HSRs). This article reviews the current knowledge on
      the genetic background of HSRs and its relevance to Jewish and Arab populations.
      The focus is on human leukocyte antigen (HLA) alleles and haplotypes as
      predictive markers of HSRs ("immunopharmacogenetics"), but other genes and
      alleles are described as well. Also discussed is the translation of the
      pharmacogenetic information to practice recommendations.

PMID- 30225835
TI  - Clinical Implications of Extensive Lymph Node Metastases for Resected Pancreatic
      Cancer.
AB  - BACKGROUND: Outcomes of patients with resected pancreatic ductal adenocarcinoma
      (PDA) and extensive lymph node metastases have not been fully characterized.
      METHODS: A total of 637 patients underwent resection for pancreatic ductal
      adenocarcinoma (PDA) between 2002 and 2014 at the Thomas Jefferson University.
      Positive lymph node count (LNC) and positive lymph node ratio (LNR) were analyzed
      as predictors of cancer-specific outcomes, with a focus on outcomes of patients
      with extensive lymph node burden. RESULTS: Resected patients with regional lymph
      node metastases had a median survival of 17.1 months (n = 425, 70%) compared with
      25.5 months (n = 185, 30%) for patients without lymph node spread (N0) (hazard
      ratio [HR] = 1.9, p < 0.001). Overall survival decremented with increased lymph
      node spread, but plateaued for LNC >= 4 (HR 2.4 vs. N0, p < 0.001) and LNR >= 0.4
      (HR 2.2, p < 0.001). Compared with historical cohorts with macroscopic metastatic
      disease, as opposed to microscopic, superior long-term survival was achieved in
      patients with extensive lymph node metastases (LNC >= 4); 24- and 36-month
      survivals were 25% (vs. 16%, p < 0.001) and 12% (vs. 6%, p < 0.001),
      respectively. Extensive lymph node burden was associated with increased baseline
      postoperative serum CA 19-9 (p = 0.044) and systemic recurrence (p < 0.001).
      CONCLUSIONS: The prognostic impact of extensive lymph node spread after resection
      for PDA plateaus above a specific threshold (LNC >= 4 or LNR >= 0.4), supporting
      the new 8th edition AJCC criteria for N2 disease. Clinically, lymph node spread
      above this threshold seems to correlate with occult systemic disease (elevated
      postoperative CA 19-9 and systemic pattern of failure).

PMID- 30225836
TI  - Frozen Section to Detect Empty Nodes and Improve the Accuracy of the Sentinel
      Lymph Node Biopsy in Endometrial Cancer.

PMID- 30225837
TI  - Contemporary Epstein Criteria with Biopsy-Naive Multiparametric Magnetic
      Resonance Imaging to Prevent Incorrect Assignment to Active Surveillance in the
      PI-RADS Version 2.0 Era.
AB  - PURPOSE: The aim of this study is to evaluate the effectiveness of
      multiparametric magnetic resonance imaging (mp-MRI) in prostate cancer (PCa)
      patients with biopsy Gleason score <= 6 who may otherwise be assigned to active
      surveillance (AS). PATIENTS AND METHODS: This was a retrospective study of 90
      patients who underwent transrectal systematic biopsy for prostate cancer with
      Gleason score <= 6 without neoadjuvant therapy, with radical prostatectomy (RP)
      conducted between September 2009 and March 2018. All patients underwent prebiopsy
      mp-MRI. The prostate imaging reporting and data system (PI-RADS) version 2.0
      score was evaluated. The correlation between imaging results and pathological
      findings was analyzed. We established models based on Epstein criteria with or
      without PI-RADS score and evaluated their ability for screening of potential PCa
      AS candidates. RESULTS: Among 90 patients, 60 (66.7%) had upgrade (Gleason >= 7),
      30 (33.3%) had extraprostatic extension, and 9 (10%) had seminal vesicle invasion
      on RP specimens. The rate of unfavorable disease was 67.8% (61 of 90). On
      multivariate analysis, independent risk factors for unfavorable disease were
      prostate-specific antigen density and PI-RADS score. The model based on Epstein
      criteria with PI-RADS score showed improved integrated discrimination improvement
      index and was superior to the classical Epstein criteria on decision curve
      analysis for screening potential prostate cancer AS candidates. CONCLUSIONS:
      Multiparametric MRI with PIRADS 2.0 provides useful supplementary information to
      Epstein criteria, and may prevent incorrect assignment to active surveillance.

PMID- 30225839
TI  - ?

PMID- 30225838
TI  - Prognostic Value of Preoperative Nutritional and Immunological Factors in
      Patients with Pancreatic Ductal Adenocarcinoma.
AB  - BACKGROUND: Preoperative nutritional and immunological patient factors have been
      found to be associated with prognostic outcomes of malignant tumors; however, the
      clinical significance of these factors in pancreatic ductal adenocarcinoma (PDAC)
      remains controversial. OBJECTIVE: The aim of this study was to evaluate the
      prognostic value of nutritional and immunological factors in predicting survival
      of patients with PDAC. METHODS: Retrospective studies of 329 patients who
      underwent surgical resection for PDAC and 95 patients who underwent palliative
      surgery were separately conducted to investigate the prognostic impact of tumor
      related factors and patient-related factors, including Glasgow Prognostic Score
      (GPS), modified GPS, Prognostic Nutritional Index (PNI), neutrophil/lymphocyte
      ratio (NLR), platelet/lymphocyte ratio, and lymphocyte/monocyte ratio. RESULTS:
      In multivariate analysis for patients with surgical resection for PDAC, PNI was
      an independent factor for overall survival (OS) and disease-free survival. The
      median OS of patients with PNI <= 45 was significantly shorter than that of
      patients with PNI > 45 (17.5 and 36.2 months, respectively; p < 0.001). In
      multivariate analysis for patients undergoing palliative surgery for PDAC, only
      NLR was an independent prognosis factor. The median OS of patients with NLR > 5
      was significantly shorter than that of patients with NLR <= 5 (2.7 and 8.9
      months, respectively; p < 0.001). CONCLUSIONS: PNI in patients with surgical
      resection and NLR in patients with palliative surgery for PDAC may be useful
      prognostic factors.

PMID- 30225840
TI  - Response to "Clinical Factors and Rate of Cough During Angiotensin-Converting
      Enzyme Inhibitor Treatment".

PMID- 30225841
TI  - Full: Ontogenesis and development of the nonhuman primate pulvinar.
AB  - Recent evidence demonstrates that the pulvinar nuclei play a critical role in
      shaping the connectivity and function of the multiple cortical areas they
      connect. Surprisingly, however, little is known about the development of this
      area, the largest corpus of the thalamic nuclei, which go on to occupy 40% of the
      adult thalamus in the human. It was proposed that the nonhuman primate and the
      human pulvinar develop according to very different processes, with a greatly
      reduced neurogenic period in nonhuman primate compared to human and divergent
      origins. In the marmoset monkey, we demonstrate that neurons populating the
      pulvinar are generated throughout gestation, suggesting that this aspect of
      development is more similar to the human than first predicted. While we were able
      to confirm the diencephalic source of pulvinar neurons, we provide new evidence
      contesting the presence of an additional niche in the telencephalon. Finally, our
      study defines new molecular markers that will simplify future investigations in
      the development and evolution of the pulvinar.

PMID- 30225842
TI  - A comparison of mosquito densities, weather and infection rates of Aedes aegypti
      during the first epidemics of Chikungunya (2014) and Zika (2016) in areas with
      and without vector control in Puerto Rico.
AB  - In Puerto Rico, the first records of the transmission of Chikungunya (CHIKV) and
      Zika (ZIKV) viruses were confirmed in May 2014 and December 2015, respectively.
      Transmission of CHIKV peaked in September 2014, whereas that of ZIKV peaked in
      August 2016. The emergence of these mosquito-transmitted arboviruses in the
      context of a lack of human population immunity allowed observations of whether
      the outbreaks were associated with Aedes aegypti (Diptera: Culicidae) densities
      and weather. Mosquito density was monitored weekly in four communities using
      sentinel autocidal gravid ovitraps (AGO traps) during 2016 in order to provide
      data to be compared with the findings of a previous study carried out during the
      2014 CHIKV epidemic. Findings in two communities protected against Ae. aegypti
      using mass AGO trapping (three traps per house in most houses) were compared with
      those in two nearby communities without vector control. Mosquito pools were
      collected to detect viral RNA of ZIKV, CHIKV and dengue virus. In areas without
      vector control, mosquito densities and rates of ZIKV detection in 2016 were
      significantly higher, similarly to those observed for CHIKV in 2014. The density
      of Ae. aegypti in treated sites was less than two females/trap/week, which is
      similar to the putative adult female threshold for CHIKV transmission. No
      significant differences in mosquito density or infection rates with ZIKV and
      CHIKV at the same sites between years were observed. Although 2016 was
      significantly wetter, mosquito densities were similar.

PMID- 30225843
TI  - Switching from ticagrelor to clopidogrel in patients with ST-segment elevation
      myocardial infarction undergoing successful percutaneous coronary intervention in
      real-world China: Occurrences, reasons, and long-term clinical outcomes.
AB  - BACKGROUND: Although switching between ticagrelor and clopidogrel is common in
      clinical practice, the efficacy and safety of this de-escalation remain
      controversial. HYPOTHESIS: We assessed the occurrences, reasons, and outcomes of
      switching from ticagrelor to clopidogrel in patients with ST-segment elevation
      myocardial infarction (STEMI) undergoing successful primary percutaneous coronary
      intervention (PCI). METHODS: A total of 653 patients with STEMI were randomly
      assigned to receive loading dose of ticagrelor or clopidogrel before PCI and then
      received maintenance dose, respectively, for 12 months follow-up. The primary
      outcome was major adverse cardiac events (MACE), including cardiovascular death,
      nonfatal myocardial infarction, and stroke. The secondary outcome included
      unexpected rehospitalization for angina, coronary revascularization, and stent
      thrombosis. The safety outcome was bleeding described by the Bleeding Academic
      Research Consortium (BARC) criteria. RESULTS: A total of 602 participants
      completed the study. The rate of switching from ticagrelor to clopidogrel was
      48.6% and the main reason was financial burden. The rate of secondary ischemic
      events in the de-escalation group was higher than that in the ticagrelor group
      (15.1% vs 5.6%, P = 0.008), but lower than that in the clopidogrel group (15.1%
      vs 24.6%, P = 0.03), while there were no significant differences in MACE among
      the three groups (P = 0.16). De-escalation, ticagrelor, and clopidogrel did not
      cause significant differences in the rates of major bleeding among the three
      groups (BARC >= 2, P = 0.34). CONCLUSION: Switching from ticagrelor to
      clopidogrel is very common in patients with STEMI in China. De-escalation might
      be safe but associated with high risk of ischemic events as compared to
      ticagrelor.

PMID- 30225844
TI  - Feasibility of desensitizing children highly allergic to peanut by high-dose oral
      immunotherapy.
AB  - BACKGROUND: There are limited data on the feasibility, efficacy and safety of
      high-dose oral immunotherapy (OIT) in children highly allergic to peanuts.
      OBJECTIVE: In children highly allergic to peanut, we primarily aimed to determine
      the feasibility of reaching the maximum maintenance dose (MMD) of 5000 mg peanut
      protein or, alternatively, a lower individual maintenance dose (IMD), by OIT up
      dosing. Secondarily, we aimed to identify adverse events (AEs) and determine
      factors associated with reaching a maintenance dose. METHODS: The TAKE-AWAY
      peanut OIT trial enrolled 77 children 5-15 years old, with a positive oral peanut
      challenge. Fifty-seven were randomized to OIT with biweekly dose step-up until
      reaching MMD or IMD and 20 to observation only. Demographic and biological
      characteristics, AEs, medication and protocol deviations were explored for
      associations with reaching maintenance dose. RESULTS: All children had
      anaphylaxis defined by objective symptoms in minimum two organ systems during
      baseline challenge. The MMD was reached by 21.1%, while 54.4% reached an IMD of
      median (minimum, maximum) 2700 (250, 4000) mg peanut protein, whereas 24.5%
      discontinued OIT. During up-dosing, 19.4% experienced anaphylaxis. Not reaching
      the MMD was caused by distaste for peanuts (66.7%), unacceptable AEs (26.7%) and
      social reasons (6.7%). Increased peanut s-IgG4 /s-IgE ratio (OR [95% CI]: 1.02
      [1.00, 1.04]) was associated with reaching MMD. CONCLUSION: Although 75.5% of
      children with peanut anaphylaxis reached a maintenance dose of 0.25-5 g, only
      21.1% reached the MMD. Distaste for peanuts and AEs, including high risk of
      anaphylaxis, limited the feasibility of reaching MMD.

PMID- 30225845
TI  - Left atrial voltage mapping using a new impedance-based algorithm in patients
      with paroxysmal atrial fibrillation.
AB  - AIMS: Atrial fibrosis is associated with the pathogenesis and progression of
      atrial fibrillation (AF). We sought to evaluate the extent of left atrial (LA)
      scarring in patients with paroxysmal AF (PAF) undergoing catheter ablation using
      a new impedance-based algorithm. METHODS: We prospectively enrolled 73
      consecutive patients (43 males, 58 years) with PAF who underwent pulmonary vein
      antral isolation. We first performed high-density bipolar voltage mapping during
      sinus rhythm using Tissue Proximity Indicator (TPI), one of the features of the
      ConfiDense mapping module integrated in the electroanatomic mapping system. A
      dense LA shell was created initially without TPI (mean points 2,411) and
      subsequently activating TPI (mean points 1,167). Each point was classified
      according to the peak-to-peak bipolar voltage electrogram based on two criteria
      (criterion A: healthy >0.8 mV, border zone: 0.4-0.8 mV, scarred: <0.4 mV;
      criterion B: healthy: >0.5 mV, border zone: 0.25-0.5 mV, scarred: <0.25 mV).
      RESULTS: LA voltage analysis represented significantly smaller scarred areas when
      mapping was performed with TPI-ON compared with TPI-OFF in both voltage criteria
      (average LA voltage area: 3.02 +/- 5.28 cm2 vs 9.15 +/- 13.11 cm2 vs in criterion
      A and 1.19 +/- 2.54 cm2 vs 5.61 +/- 9.56 cm2 in criterion B). A statistically
      significant voltage difference was observed in all segments of the left atrium
      between the two mapping protocols, particularly on the inferior wall. CONCLUSION:
      A more specific delineation of LA fibrosis may be produced using the TPI feature
      of the ConfiDense mapping module, through elimination of false-positive annotated
      mapping points due to low contact.

PMID- 30225846
TI  - Differentiating factitious psychological presentations from malingering:
      Implications for forensic practice.
AB  - Practitioners and researchers have long been challenged with identifying
      deceptive response styles in forensic contexts, particularly when differentiating
      malingering from factitious presentations. The origins and the development of
      factitious disorders as a diagnostic classification are discussed, as well as the
      many challenges and limitations present with the current diagnostic
      conceptualization. As an alternative to a formal diagnosis, forensic
      practitioners may choose to consider most factitious psychological presentations
      (FPPs) as a dimensional construct that are classified like malingering as a V
      code. Building on Rogers' central motivations for malingering, the current
      article provides four explanatory models for FPPs; three of these parallel
      malingering (pathogenic, criminological, and adaptational) but differ in their
      central features. In addition, the nurturance model stresses how patients with
      FPPs attempt to use their relationship with treating professionals to fulfill
      their unmet psychological needs. Relying on these models, practical guidelines
      are recommended for evaluating FPPs in a forensic context.

PMID- 30225847
TI  - Is it time to reconsider the classic neurological examination?

PMID- 30225848
TI  - Quantitative assessment of heavy metal effects on sperm function using computer
      aided sperm analysis and cytotoxicity assays.
AB  - One known environmental risk factor impacting on human reproduction is heavy
      metal pollution. Although some metals (e.g., Cu, Se and Zn) have protective
      effects on the male reproductive system in low doses, heavy metals can accumulate
      to toxic levels and result in poor semen quality and decreased sperm function. We
      investigated the effect of CuSO4 and CdCl2 (10, 50, 100 and 250 ug/ml or 500
      ug/ml) on human sperm motility and vitality by using computer-aided sperm
      analysis (CASA) and two cytotoxicity assays (WST-1 and XTT). Several sperm
      motility parameters were significantly reduced after 5 hr of exposure to the
      highest concentrations of CuSO4 (250 ug/ml) and CdCl2 (500 ug/ml). The WST-1
      assay also revealed significantly lower absorbance values for 50, 100 and 250
      ug/ml CuSO4 and for 500 ug/ml CdCl2 ; however, no significant effect was seen
      with XTT. The calculated average IC50 value was 50.31+/-  4.34 ug/ml for CuSO4
      and 392.32  +/-76.79 ug/ml for CdCl2 . The effects of these metals were confirmed
      with MgCl2 , a positive control. This study provides threshold concentrations for
      the harmful effect of CuSO4 and CdCl2 on human spermatozoa and recommends the use
      of WST-1 as vitality assay in future in vitro studies.

PMID- 30225849
TI  - Defining the balance point between conservation and development.
AB  - In the face of the current global ecological crisis and the threats it poses to
      human survival and security, the fundamental solution is to resolve the deep
      contradiction between conservation and economic development. We considered the 3
      key and basic questions of why to protect, how much to protect, and where to
      protect natural areas. Human survival depends on functioning ecosystems and the
      ecosystem services they provide. In this regard, conserving core biodiversity
      conservation priority areas (BCPAs) can provide maximum conservation benefit. The
      goals of protected area (PA) systems globally and nationally must be clearly
      defined so as to sustain the survival and development of people and to coordinate
      and balance other objectives with this goal at the center. There is an urgent
      need to study, calculate, and define the extent of the natural world to ensure
      the well-being of people. We call this area over which natural areas of land and
      sea extend across the world or a country nature proportion (N%). Especially, a
      minimum area that ensures human survival should be protected, and we suggest that
      this area should cover core BCPAs so that it can achieve the maximum conservation
      benefit. These recommendations could be applied at global or national levels. The
      Chinese government proposes "developing a protected-area system composed mainly
      of national parks," and it has unified the administration of PAs into a central
      management authority. At this key time in the reform of the PA system, should
      this proposal be adopted, conservation will garner the greatest social consensus
      and support, and planning at the national level for BCPA coverage will be
      improved. We believe these recommendations are critical for China and other
      countries and extremely important for the world because they will pave the way
      toward a balance between nature conservation and human development as the
      projected human population reaches 10 billion by 2050.

PMID- 30225850
TI  - Effect of dietary supplementation with Yarrowia lipolytica or Saccharomyces
      cerevisiae yeast and probiotic additives on growth performance, basic nutrients
      digestibility and biochemical blood profile in piglets.
AB  - The objective of the study was to compare the efficiency of dietary
      supplementation of two species of yeast, Yarrowia lipolytica (YL) and
      Saccharomyces cerevisiae (SC), with or without the addition of a probiotic, on
      growth performance, basic nutrients digestibility and blood profile in piglets.
      The experiment was conducted on 360 weaned piglets (180 barrows and 180 gilts).
      Each treatment comprised 60 piglets. The piglets (27-day-old) were assigned to
      the following dietary treatments: (a) basal control (C) diet, (b) C diet +
      probiotic (Bacillus licheniformis and Bacillus subtilis-2 * 109  CFU/kg of feed),
      (c) C diet + 3% Y. lipolytica (YL-2 * 1010  CFU/g), (d) C diet + 3%YL +
      probiotic, (e) C diet + 3% S. cerevisiae (SC-3 * 1010  CFU/g) and (f) C diet + 3%
      SC + probiotic. Blood for analysis was collected from a total of 36 piglets at
      the end of the experiment, that is, 56 days after weaning. During the entire
      experiment, significantly greater weight gain was observed in the piglets
      receiving YL. The addition of the probiotic supplement and SC yeast reduced the
      daily feed intake during day 16-56 and from day 0 to 56 of the experiment. A
      better feed conversion ratio (FCR) during day 0-56 of the experiment was noted
      after addition of the probiotic and yeast. The use of YL yeast in diets for
      piglets had a more beneficial effect on weight gain and FCR than SC. Moreover,
      the addition of YL modulates lipid metabolism in piglets, as indicated by the
      reduced levels of TCH, LDL and TG and increased level of HDL in the plasma. The
      combined use of either YL or SC with a probiotic is not recommended in piglet
      rearing, as it does not substantially improve growth performance and health in
      comparison with yeast alone.

PMID- 30225851
TI  - Do interventions containing risk messages increase risk appraisal and the
      subsequent vaccination intentions and uptake? - A systematic review and meta
      analysis.
AB  - PURPOSE: There is good evidence that for many behaviours, increasing risk
      appraisal can lead to a change in behaviour, heightened when efficacy appraisals
      are also increased. The present systematic review addressed whether interventions
      presenting a risk message increase risk appraisal and an increase in vaccination
      intentions and uptake. METHOD: A systematic search identified randomized
      controlled trials of interventions presenting a risk message and measuring risk
      appraisal and intentions and uptake post-intervention. Random-effects meta
      analyses investigated the size of the effect that interventions had on
      vaccination risk appraisal and on vaccination behaviour or intention to
      vaccinate, and the size of the relationship between vaccination risk appraisal
      and vaccination intentions and uptake. RESULTS: Eighteen studies were included
      and 16 meta-analysed. Interventions overall had small significant effects on risk
      appraisal (d = 0.161, p = .047) and perceptions of susceptibility (d = 0.195, p =
      .025), but no effect on perceptions of severity (d = -0.036, p = .828).
      Interventions showed no effect on intention to vaccinate (d = 0.138, p = .195)
      and no effect on vaccination behaviour (d = 0.043, p = .826). Interventions
      typically did not include many behaviour change techniques (BCTs), with the most
      common BCT unique to intervention conditions being 'Information about Health
      Consequences'. Few of the included studies attempted to, or successfully
      increased, efficacy appraisals. CONCLUSIONS: Overall, there is a lack of good
      quality primary studies, and existing interventions are suboptimal. The inclusion
      of additional BCTs, including those to target efficacy appraisals, could increase
      intervention effectiveness. The protocol (CRD42015029365) is available from
      http://www.crd.york.ac.uk/PROSPERO/. Statement of contribution What is already
      known on this subject? Previous research indicates that an increase in risk
      appraisal is associated with increased uptake in health-related behaviours.
      Research suggests that interventions increasing risk appraisal have a greater
      effect on intention when elements of efficacy appraisals are simultaneously
      increased. What does this study add? This is the first systematic review to
      examine the effect of interventions on risk appraisal and vaccination uptake
      using only experimental studies. Limitations of the interventions themselves, and
      those caused by study methods and reporting, mean that the potential value of
      this type of review is lost. Instead, its value is in shining a light on the
      paucity of experimental studies in this area, and the quality of methods and
      reporting used. Future experimental studies should examine interventions that
      focus exclusively on increasing risk and efficacy appraisal compared to controls,
      use conditional measures of risk, and improve reporting to enable both more
      accurate coding of intervention content and more accurate assessments of study
      bias.

PMID- 30225852
TI  - Lime powder regimen supplement alleviates urinary metabolic abnormalities in
      urolithiasis patients.
AB  - BACKGROUND: Urolithiasis has high recurrent rate after surgical removal within 3
      years. Potassium citrate compound is used to prevent stone recurrence but it has
      intolerable gastrointestinal adverse effects. We conducted a phase 2 clinical
      study of lime power regimen (LPR), a limeade-based supplement containing
      potassium and citrate for 6-month period of treatment, to evaluate its effects on
      biochemical and clinical aspects of recurrent urolithiasis. METHODS: Seventy-four
      urolithiasis patients were randomly allocated to receive either LPR or placebo
      for 6 months in a double blinded manner. Plasma and 24-hour urine samples were
      collected to measure urinary pH, mineral excretion and total antioxidant status
      (U-TAS), plasma for creatinine and plasma protein carbonyl, and stone for
      elemental analysis at the initiation and end-of-treatment (6 month). Adverse
      effects were recorded. RESULTS: Administration of LPR significantly increased
      urinary pH, citrate and potassium excretion. Urinary levels of calcium and
      oxalate, and plasma protein carbonyl content were reduced, while U-TAS was
      elevated by LPR treatment. Urinary supersaturation was decreased and urinary
      protein excretion was ameliorated in LPR-treated patients. Gastrointestinal
      adverse effects were rarely. None of the participants developed stone recurrence
      for the duration of the trial. CONCLUSIONS: LPR is a potential drug to correct
      urinary metabolic disorders associated with urolithiasis in high risk stone
      recurrent patients. A phase 3 clinical trial is underway to validate anti-stone
      recurrence property of LPR in long-term treatment. This article is protected by
      copyright. All rights reserved.

PMID- 30225853
TI  - Inflammasome activation during spontaneous preterm labor with intra-amniotic
      infection or sterile intra-amniotic inflammation.
AB  - PROBLEM: The inflammasome is implicated in the mechanisms that lead to
      spontaneous preterm labor (PTL). However, whether there is inflammasome
      activation in the amniotic cavity of women with PTL and intra-amniotic infection
      (IAI) or sterile intra-amniotic inflammation (SIAI) is unknown. METHOD OF STUDY:
      Amniotic fluid samples were collected from women with PTL who delivered at term
      (n = 31) or preterm without IAI or SIAI (n = 35), with SIAI (n = 27), or with IAI
      (n = 17). As a readout of inflammasome activation, extracellular ASC (apoptosis
      associated speck-like protein containing a CARD) was measured in amniotic fluid
      by ELISA and the expression of ASC, caspase-1, and interleukin (IL)-1beta was
      detected in the chorioamniotic membranes by multiplex immunofluorescence. Acute
      inflammatory responses in amniotic fluid and the placenta were also evaluated.
      RESULTS: (a) Amniotic fluid concentrations of ASC and IL-6 were higher in women
      with PTL and IAI or SIAI than in those who delivered preterm or at term without
      intra-amniotic inflammation; (b) amniotic fluid concentrations of ASC and IL-6
      were lower in women with PTL and SIAI than in those with IAI; (c) there was a
      significant nonlinear correlation between ASC and IL-6 amniotic fluid
      concentrations; (d) the expression of inflammasome-related proteins (ASC, caspase
      1, and IL-1beta) in the chorioamniotic membranes was increased in women with PTL
      and IAI or SIAI than in those who delivered preterm or at term without intra
      amniotic inflammation; (e) inflammasome activation in the chorioamniotic
      membranes was weaker in women with PTL and SIAI than in those with IAI; (f) women
      with PTL and IAI had elevated amniotic fluid white blood cell counts compared to
      those without this clinical condition; and (g) severe acute placental
      inflammatory lesions were observed in women with PTL and IAI and in a subset of
      women with PTL and SIAI. CONCLUSION: Inflammasome activation occurs in the
      settings of intra-amniotic infection and sterile intra-amniotic inflammation
      during spontaneous preterm labor.

PMID- 30225854
TI  - Origin and phylogenetic relationships of [4Fe-4S]-containing O2 sensors of
      bacteria.
AB  - The advent of environmental O2 about 2.5 billion years ago forced microbes to
      metabolically adapt and to develop mechanisms for O2 sensing. Sensing of O2 by
      [4Fe-4S]2+ to [2Fe-2S]2+ cluster conversion represents an ancient mechanism that
      is used by FNREc (Escherichia coli), FNRBs (Bacillus subtilis), NreBSa
      (Staphylococcus aureus) and WhiB3Mt (Mycobacterium tuberculosis). The
      phylogenetic relationship of these sensors was investigated. FNREc homologues are
      restricted to the proteobacteria and a few representatives from other phyla.
      Homologues of FNRBs and NreBSa are located within the bacilli, of WhiB3 within
      the actinobacteria. Archaea contain no homologues. The data reveal no similarity
      between the FNREc , FNRBs , NreBSa and WhiB3 sensor families on the sequence and
      structural levels. These O2 sensor families arose independently in phyla that
      were already present at the time O2 appeared, their members were subsequently
      distributed by lateral gene transfer. The chemistry of [4Fe-4S] and [2Fe-2S]
      cluster formation and interconversion appears to be shared by the sensor protein
      families. The type of signal output is, however, family specific. The homologues
      of FNREc and NreBSa vary with regard to the number of Cys residues that
      coordinate the cluster. It is suggested that the variants derive from lateral
      gene transfer and gained other functions.

PMID- 30225855
TI  - The Diverse Reactivity of Disilenes Toward Isocyanides.
AB  - The addition of 2,6-dimethylphenyl isocyanide and t-butyl isocyanide to
      tetramesityldisilene was examined. In both cases, the initially formed product is
      an iminodisilirane; however, the iminodisiliranes are unstable under the reaction
      conditions and react with a second equivalent of the isocyanide to give either a
      3-silaazetidine or a novel bicyclic double enamine, respectively. Taken together
      with the previous examples in the literature, the results demonstrate that subtle
      differences in the steric bulk of the disilene or the electronic effects of the
      isocyanide can lead to dramatic differences in the reaction pathway.

PMID- 30225856
TI  - Aortoduodenal syndrome: a rare cause of duodenal obstruction in a patient with
      previous aortic aneurysm repair.

PMID- 30225858
TI  - Stabilizing n-Type Cubic GeSe by Entropy-Driven Alloying of AgBiSe2 : Ultralow
      Thermal Conductivity and Promising Thermoelectric Performance.
AB  - The realization of n-type Ge chalcogenides is elusive owing to intrinsic Ge
      vacancies that make them p-type semiconductors. GeSe crystallizes into a layered
      orthorhombic structure similar to SnSe at ambient conditions. The high-symmetry
      cubic phase of GeSe is predicted to be stabilized by applying 7 GPa external
      pressure or by enhancing the entropy by increasing to temperature to 920 K.
      Stabilization of the n-type cubic phase of GeSe at ambient conditions was
      achieved by alloying with AgBiSe2 (30-50 mol %), enhancing the entropy through
      solid solution mixing. The interplay of positive and negative chemical pressure
      anomalously changes the band gap of GeSe with increasing the AgBiSe2
      concentration. The band gap of n-type cubic (GeSe)1-x (AgBiSe2 )x (0.30<=x<=0.50)
      has a value in the 0.3-0.4 eV range, which is significantly lower than
      orthorhombic GeSe (1.1 eV). Cubic (GeSe)1-x (AgBiSe2 )x exhibits an ultralow
      lattice thermal conductivity (kappaL ~0.43 W m-1  K-1 ) in the 300-723 K range.
      The low kappaL is attributed to significant phonon scattering by entropy-driven
      enhanced solid-solution point defects.

PMID- 30225857
TI  - Development of the Dementia Assessment Sheet for Community-based Integrated Care
      System 8-items, a short version of the Dementia Assessment Sheet for Community
      based Integrated Care System 21-items, for the assessment of cognitive and daily
      functions.
AB  - AIM: The present study aimed to: (i) examine the reliability and validity of the
      Dementia Assessment Sheet for Community-based Integrated Care System 21-items for
      classifying patients to the appropriate categories for glycemic targets in older
      patients; and (ii) develop a short version of the tool and examine its
      reliability and validity. METHODS: A total of 410 older individuals were
      recruited for this multicenter cross-sectional study. We classified them into
      three categories used for determining the glycemic target in older patients in
      Japan based on cognitive functions and activities of daily living. Exploratory
      factor analyses were used to select the eight items of the shorter version. The
      reliability and validity of the assessment tools were assessed using Cronbach's
      alpha coefficients and receiver operating characteristic analyses, respectively.
      RESULTS: The Dementia Assessment Sheet for Community-based Integrated Care System
      21-items had three latent factors: cognitive function, instrumental activities of
      daily living and basic activities of daily living. The Dementia Assessment Sheet
      for Community-based Integrated Care System 8-items was developed based on each
      factor load quantity and was confirmed to have a strong correlation with the
      original version (r = 0.965, P < 0.001). Both tools significantly discriminated
      older adults belonging to category I from those belonging to category II or III,
      and category III from category I or II. CONCLUSIONS: Both tools had sufficient
      internal consistency and validity to classify older patients into the categories
      for determining the glycemic target in this population based on cognitive and
      daily functions. Geriatr Gerontol Int 2018; 18: 1458-1462.

PMID- 30225859
TI  - Dietary energy density is associated with body mass index-for-age in Mexican
      adolescents.
AB  - Dietary energy density (DED) has been widely considered a risk factor for weight
      gain. In adolescents, however, the evidence is inconclusive, and in Mexico, the
      ways in which DED is associated with overweight and obesity are unknown. Our
      study analysed the association of DED with overweight or obesity (OW-O) in
      Mexican adolescents included in the National Health and Nutrition Survey 2012
      (ENSANUT 2012). We analysed the data from a 7-day Food Frequency Questionnaire
      administered to 2,203 Mexican adolescents aged 12-19 years. DED was calculated
      excluding all beverages. Plausible and implausible reporters were identified
      based on the relationship between the reported energy intake and the estimated
      energy requirement. The association of DED with body mass index (BMI)-for-age and
      OW-O was analysed using multivariate statistical models restricted to plausible
      reporters. The combined prevalence of overweight and obesity was 35.4% in the
      complete sample and 27.8% in the sample of plausible reporters. Mean DED was 177
      kcal/100 g, with higher DED in the north of the country. The proportion of
      plausible reporters was 38.5%. We found a positive association between high DED
      and the BMI-for-age z-score (beta = 0.347; 95% CI [0.101, 0.594]; P = 0.006),
      controlling for sociodemographic and dietary variables, but no significant
      association with OW-O. It is necessary to consider the DED in the design and
      implementation of strategies to reduce energy density in the diets of young
      Mexicans.

PMID- 30225860
TI  - In vivo dynamic thermal imaging of skin radiofrequency treatment.
AB  - In recent years, popularity of radiofrequency (RF) has increased significantly.
      They are characterized by a low risk of complications and relatively high
      effectiveness. RF use high-frequency currents causing oscillating motion of ions
      resulting in temperature rise stimulating skin regeneration processes. The aim of
      this work was the thermographic evaluation of the skin exposed to RF of different
      intensity. The dynamic thermal imaging was used to study the temperature of the
      skin exposed to RF. The research was carried out in two locations with different
      adipose tissue content: abdomen (ROI1) and forearm (ROI2). In the ROI1 area, RF
      was applied at nominal power range from 250 to 1750 W, while in ROI2 area: from
      250 to 1000 W. The obtained thermographic data were fitted to exponential
      functions. A clear dependence of obtained thermokinetic parameters with the
      anatomical location of exposure to RF was demonstrated. Thicker layer of adipose
      tissue directly under the skin resulted in obtaining higher maximum temperatures
      of the skin surface during the procedure (maximum obtained temperature equaled
      40.8 degrees C). The temperature of the skin under the head of the device does
      not translate to subjective patient experiences. In anatomic locations filled
      with less adipose tissue mass, tolerance to RF is much lower. The dynamics of
      skin temperature changes, after the RF treatment, can be described by means of a
      single exponential function where the key parameter is the time constant t1
      defining the dynamics of skin temperature changes. The depth of the RF influence
      is slightly correlated with the RF power.

PMID- 30225861
TI  - Implementation and operation of incident learning across a newly-created health
      system.
AB  - PURPOSE: The purpose of this work is to describe our experience launching an
      expanded incident learning system for patient safety and quality that takes into
      account aspects beyond therapeutic dose delivery, specifically imaging/simulation
      incidents, medical care incidents, and operational issues. METHODS: Our ILS was
      designed for a newly created health system comprised of a midsized academic
      hospital and two smaller community hospitals. The main design goal was to create
      a highly sensitive system to capture as much information throughout the
      department as possible. Reports were classified according to incidents and near
      misses involving therapeutic radiation, imaging/simulation, and patient care (not
      involving radiation), unsafe conditions, operational issues, and
      accolades/suggestions. Reports were analyzed according to impact on various steps
      in the process of care. Actions made in response to reports were assessed and
      characterized by intervention reliability. RESULTS: A total of 1125 reports were
      submitted in the first 23 months. For all three departments, therapeutic
      radiation incidents and near misses consisted of less than one-third of all
      reports submitted. For the midsized academic department, operational issues and
      unsafe conditions comprised the largest percentage of reports (70%). Although the
      majority of reports impacted steps related to the technical aspects of treatment
      (simulation, planning, and treatment delivery), 20% impacted other steps such as
      scheduling or clinic visits. More than 160 actions were performed in response to
      reports. Of these actions, 63 were quality improvement interventions to improve
      practices, while 97 were learning actions for raising awareness. CONCLUSIONS: We
      have developed an ILS that identifies issues related to the entire process of
      care delivery in radiation oncology, as evidenced by frequent and varied reported
      events. By identifying a broad spectrum of issues in a department, opportunities
      for improvement can be identified.

PMID- 30225862
TI  - Committing the primordial germ cell: An updated molecular perspective.
AB  - The germ line is a crucial cell lineage that is distinct from somatic cells, and
      solely responsible for the trans-generational transmission of hereditary
      information in metazoan sexual reproduction. Primordial germ cells (PGCs)-the
      precursors to functional germ cells-are among the first cell types to be
      allocated in embryonic development, and this lineage commitment is a critical
      event in partitioning germ line and somatic tissues. Classically, mammalian PGC
      development has been largely informed by investigations on mouse embryos and
      embryonic stem cells. Recent findings from corresponding nonrodent systems,
      however, have indicated that murine PGC specification may not be fully
      archetypal. In this review, we outline the current understanding of molecular
      mechanisms in PGC specification, emphasizing key transcriptional events, and
      focus on salient differences between early human and mouse PGC commitment. Beyond
      these latest findings, we also contemplate the future outlook of inquiries in
      this field, highlighting the importance of comprehensively understanding early
      fate decisions that underlie the segregation of this unique lineage. This article
      is categorized under: Developmental Biology > Stem Cell Biology and Regeneration
      Biological Mechanisms > Cell Fates Physiology > Mammalian Physiology in Health
      and Disease.

PMID- 30225863
TI  - Improved discrimination between normal-tension and primary open-angle glaucoma
      with advanced vascular examinations - the Leuven Eye Study.
AB  - PURPOSE: Vascular factors have been suggested to influence the development and
      progression of glaucoma. They are thought to be especially relevant for normal
      tension glaucoma (NTG) patients. We aim to investigate which vascular factors,
      including advanced vascular examinations, better describe patients with NTG
      comparing to those with primary open-angle glaucoma (POAG). METHODS: The Leuven
      Eye Study database (182 NTG and 202 POAG patients; similar structural and
      functional damage) was used to compute three multivariate logistic regression
      models: a conventional model (conventional parameters only, including vascular
      related self-reported phenomena, such as migraine or peripheral vasospasm); an
      advanced vascular model (advanced vascular parameters only: colour Doppler
      imaging (CDI), retinal oximetry, ocular pulse amplitude and choroidal thickness);
      and a global model, in which both types of parameters were allowed. Receiver
      operating characteristic (ROC) curves and corresponding areas under the curve
      (AUC) were calculated and compared between models. RESULTS: Patients with NTG had
      a higher resistive index and lower early systolic acceleration (ESA) in their
      retrobulbar vessels and a smaller arteriovenous retinal oxygen saturation
      difference. The global model (AUC 0.743) showed a significantly better
      discriminative ability when compared to either the conventional (AUC 0.687, p =
      0.049) or the advanced vascular (AUC 0.677, p = 0.005) models. Also, the
      conventional and the advanced vascular models showed a similar discriminative
      ability (p = 0.823). CONCLUSION: Patients with NTG have more signs of vascular
      dysfunction. Clinical conventional parameters, such as asking simple vascular
      related questions, combined with advanced vascular examinations provide
      information to better understand the value that non-IOP-related factors play in
      NTG.

PMID- 30225864
TI  - Left atrium function and deformation in very preterm infants with and without
      volume load.
AB  - BACKGROUND: Left atrium (LA) function can be assessed by volumetric measurements,
      conventional and tissue Doppler, and more recently, deformation imaging using two
      dimensional speckle tracking echocardiography (2DSTE). 2DSTE allows for
      measurement of volume and deformation and can quantify the contribution of the
      reservoir, conduit, and contraction phase. A common cause for LA dysfunction in
      very preterm infants is volume overload with a patent ductus arteriosus (PDA).
      The aim of this study was to explore the feasibility and reliability of LA 2DSTE
      in preterm infants, and describe LA function with and without PDA volume load.
      METHODS: We prospectively recruited preterm infants <30 weeks of gestation
      referred for assessment of a possible PDA. A cardiac ultrasound was performed at
      day 3 and in week 4 of life and analyzed using conventional techniques and 2DSTE.
      RESULTS: Forty-eight infants (32 with PDA) were included. LA 2DSTE analysis was
      feasible in 96% of measurements with good reliability of strain and volume
      parameters. Strain rate was less reliable. Poorer LA contraction and reservoir
      function was associated with larger LA volume index, higher inflow over the
      mitral valve at early diastole, higher EA ratio, and higher Ee' ratio. Poorer
      conduit function was associated with higher Ee' ratio. A larger PDA diameter was
      found to be an independent contributor to deteriorating LA contraction and
      reservoir function. CONCLUSION: LA 2DSTE analysis is feasible in preterm infants
      and provides detailed information on atrium mechanics. Further studies are needed
      to explore the clinical value of these new parameters in this population.

PMID- 30225865
TI  - Establishing Surrogate Kidney Endpoints for Lupus Nephritis Clinical Trials:
      Development and Validation of a Novel Approach to Predict Future Kidney Outcomes.
AB  - OBJECTIVE: Endpoints currently used in lupus nephritis (LN) clinical trials lack
      uniformity and questionably reflect long-term kidney survival. The objective of
      this investigation was to identify short-term endpoints that predict long-term
      kidney outcomes for use in clinical trials. METHODS: A database of 944 LN
      patients was assembled from 3 clinical trials and 12 longitudinal cohorts.
      Variables from the first 12 months of treatment after diagnosis of active LN
      (prediction period) were assessed as potential predictors of long-term outcomes
      in a 36 month follow-up period. The long-term outcomes examined were new or
      progressive chronic kidney disease (CKD), severe kidney injury (SKI), and the
      need for permanent renal replacement therapy (RRT). Hazard Index Tools (HITs) to
      predict risk for each outcome were derived using multivariable analysis with Cox
      proportional hazards regression. RESULTS: Among 550 eligible subjects 54 CKD, 55
      SKI and 22 RRT events occurred. Variables in the final CKD HIT were prediction
      period CKD status, 12-month proteinuria and12-month serum creatinine (SCr). The
      SKI HIT included prediction period CKD status, ISN Class, 12-month proteinuria,
      12-month SCr, race and an interaction between ISN Class and 12-month proteinuria.
      The RRT HIT included age at diagnosis, 12-month proteinuria and 12-month SCr.
      Each HIT validated well internally (c-indices 0.84-0.92) and in an independent LN
      cohort (c-indices 0.83-0.92). CONCLUSION: HITs, derived from short-term kidney
      responses to treatment correlate with long-term kidney outcomes, and now must be
      validated as surrogate endpoints for LN clinical trials. This article is
      protected by copyright. All rights reserved.

PMID- 30225866
TI  - Direct mechanical characterization of prostate tissue-a systematic review.
AB  - BACKGROUND: Direct mechanical characterization of tissue is the application of
      engineering techniques to biological tissue to ascertain stiffness or elasticity,
      which can change in response to disease states. A number of papers have been
      published on the application of these techniques to prostate tissue with a range
      of results reported. There is a marked variability in the results depending on
      testing techniques and disease state of the prostate tissue. We aimed to clarify
      the utility of direct mechanical characterization of prostate tissue in
      identifying disease states. METHODS: A systematic review of the published
      literature regarding direct mechanical characterization of prostate tissue was
      undertaking according to PRISMA guidelines. RESULTS: A variety of testing methods
      have been used, including compression, indentation, and tensile testing, as well
      as some indirect testing techniques, such as shear-wave elastography. There is
      strong evidence of significant stiffness differences between cancerous and non
      cancerous prostate tissue, as well as correlations with prostate cancer stage.
      There is a correlation with increasing prostate stiffness and increasing lower
      urinary tract symptoms in patients with benign prostate hyperplasia. There is a
      wide variation in the testing methods and protocols used in the literature making
      direct comparison between papers difficult. Most studies utilise ex-vivo or
      cadaveric tissue, while none incorporate in vivo testing. CONCLUSION: Direct
      mechanical assessment of prostate tissue permits a better understanding of the
      pathological and physiological changes that are occurring within the tissue.
      Further work is needed to include prospective and in vivo data to aid medical
      device design and investigate non-surgical methods of managing prostate disease.

PMID- 30225867
TI  - Circumaortic double left innominate vein: Two novel echocardiographic diagnostic
      clues for a tricky diagnosis.
AB  - We report a 7-year-old boy with unilateral choanal atresia who was referred for
      cardiac consultation before surgery. On echocardiography, the heart was normal
      except the presence of a double-circle appearance and a V-shaped structure on the
      suprasternal notch view. Cardiac computed tomography (CT) angiography confirmed
      the diagnosis of the double left innominate vein (DLIV). DLIV is a rare systemic
      venous anomaly, which often produces diagnostic confusion on echocardiography.
      Correct diagnosis is essential before performing any invasive procedure through
      this vein. Co-existence of the two echocardiographic signs of the double-circle
      appearance and the V sign confirms this tricky diagnosis.

PMID- 30225868
TI  - Successful implementation of immediate postpartum intrauterine contraception
      services in Edinburgh and framework for wider dissemination.
AB  - Provision of immediate postpartum intrauterine device (PPIUD) insertion within
      maternity settings can overcome many of the barriers faced by women in accessing
      this method after childbirth. Uptake of PPIUD can help reduce the risk of a
      subsequent unintended pregnancy and improve spacing between births. PPIUD
      insertion is not yet routinely available in the UK and evidence to support the
      practical implementation of the service in this setting is lacking. Shared
      learning and experience of providers may assist in the wider availability of
      PPIUD. A routine PPIUD service has been successfully established within a public
      maternity setting in Edinburgh (UK) and this article utilizes an implementation
      framework to discuss the approach.

PMID- 30225869
TI  - Planning and implementation of a FIGO postpartum intrauterine device initiative
      in six countries.
AB  - OBJECTIVE: To describe the process of planning and implementing a program of
      counselling and delivery of postpartum intrauterine devices (PPIUD) in 48
      hospitals across six countries in Africa and Asia. METHODS: The process of
      planning the FIGO PPIUD initiative, selection of countries and hospitals, model
      of implementation, and lessons for the future are described. RESULTS: Country
      level and hospital-based leadership were essential and training-the-trainer
      models were successful. There was a need for consistency of competency standards
      allowing for national variations. As the project progressed, additional steps
      were necessary for steady implementation of the initiative, specifically:
      establishment of a project steering committee and a data safety monitoring
      committee, audits of structure and process, and regular feedback of each center's
      performance to stimulate maintenance and enhancement of activities. Postnatal
      follow-up was challenging in many countries with fragmented maternity systems.
      CONCLUSION: The importance of professional leadership and commitment backed by
      robust data for monitoring and feedback are essential for success.

PMID- 30225870
TI  - Four years of the FIGO postpartum intrauterine device initiative in Sri Lanka:
      Pilot initiative to national policy.
AB  - OBJECTIVE: To analyze the difficulties and challenges arising from introduction
      of postpartum intrauterine device (PPIUD) services into the Sri Lankan health
      system. METHODS: Phase I of a FIGO PPIUD initiative was implemented in 2013 in
      six hospitals; phase II began in 12 hospitals in 2015. During this period, 915
      Medical Officers were trained in PPIUD insertion and 5370 personnel were trained
      in PPIUD counseling. Women were followed up at 4-6 weeks after insertion.
      RESULTS: A total of 184 433 women (62.4% of hospital deliveries) were interviewed
      about PPIUD as a method of contraception. Of those interviewed, 116 159 (63.0%)
      received counseling on PPIUD and 11 339 (6.1%) consented to PPIUD insertion. Of
      consenting women, 9346 (82.4%) had a PPIUD inserted. There were no significant
      complications reported at insertion. Expulsion rates were 2.9% and removal rates
      were 4.1%. CONCLUSION: PPIUD as a method of contraception was successfully
      introduced into the 18 participating hospitals. Given the success of this pilot
      intervention and the safety profile demonstrated, PPIUD was added to the national
      family planning program in 2017.

PMID- 30225871
TI  - Impact of contraceptive counselling training among counsellors participating in
      the FIGO postpartum intrauterine device initiative in Bangladesh.
AB  - OBJECTIVE: To evaluate the impact of structured training given to dedicated
      family planning counsellors on postpartum intrauterine device (PPIUD) services
      across six tertiary hospitals in Bangladesh. METHODS: Family planning counsellors
      underwent structured training on postpartum family planning, PPIUD in particular,
      over a four-day period. Impact of training was evaluated by comparing PPIUD
      counselling rates, consent rates, insertion rates, and removal rates five months
      before and five months after the training, using data from women delivering in
      the participating facilities. RESULTS: A total of 27 622 women were included in
      this analysis: 11 263 (40.8%) before the training intervention and 16 359 (59.2%)
      after it. There was an increase in the proportion of women who were counselled
      (from 75.3% to 83.8%, P<0.001), and a small decrease in the proportion of women
      agreeing to have a PPIUD inserted following counselling (13.7% vs 12.9%, P=0.03).
      Overall insertion rate was similar before and after training (9.5% vs 9.8%,
      P=0.42), while removal rate reduced from 2.8% to 1.8% (P=0.41). CONCLUSION:
      Structured training had no impact on overall PPIUD insertion rate. However, it
      did impact numbers of women receiving counselling, perceived quality of the
      counselling received, and overall removal rates.

PMID- 30225872
TI  - Institutionalization of postpartum intrauterine devices.

PMID- 30225873
TI  - FIGO postpartum intrauterine device initiative: Complication rates across six
      countries.
AB  - OBJECTIVE: To record and analyze complication rates following postpartum
      intrauterine device (PPIUD) insertion in 48 hospitals in six countries: Sri
      Lanka, India, Nepal, Bangladesh, Tanzania, and Kenya. METHODS: Healthcare
      providers were trained in counselling and insertion of PPIUD via a training-the
      trainer model. Data were collected on methodology, timing, cadre of staff
      providing care, and number of insertions. Data on complications were collected at
      6-week follow-up. Statistical analysis was performed to elucidate factors
      associated with increased expulsion and absence of threads. RESULTS: From May
      2014 to September 2017, 36 766 PPIUDs were inserted: 53% vaginal and 47% at
      cesarean delivery; 74% were inserted by doctors. Follow-up was attended by 52%.
      Expulsion and removal rates were 2.5% and 3.6%, respectively. Threads were not
      visible in 29%. Expulsion was less likely after cesarean insertion (aOR 0.33; 95%
      CI, 0.26-0.41), following vaginal insertion at between 10 minutes and 48 hours
      (aOR 0.59; 95% CI, 0.42-0.83), and when insertion was performed by a nurse (aOR
      0.33; 95% CI, 0.22-0.50). CONCLUSION: PPIUD has low complication rates and can be
      safely inserted by a variety of trained health staff. Given the immediate benefit
      of the one-stop approach, governments should urgently consider adopting this
      model.

PMID- 30225875
TI  - Clinical outcomes of postpartum intrauterine devices inserted by midwives in
      Tanzania.
AB  - OBJECTIVE: To assess the rate of complications following immediate postpartum
      insertion of intrauterine devices (IUDs) by trained midwives in Tanzania.
      METHODS: A prospective cohort study of women who underwent immediate postpartum
      IUD (PPIUD) insertions provided by midwives between December 31, 2016 and October
      15, 2017. Midwives received standardized training via the FIGO initiative. Women
      who returned 6 weeks after delivery were evaluated for complications. Outcomes of
      interest were uterine infection, IUD expulsion, medical removal of IUD, and
      method discontinuation. RESULTS: There were 40 470 deliveries, 2347 (5.8%) PPIUD
      insertions, and 1013 (43.2%) women with a PPIUD who returned for a follow-up
      visit in the program-affiliated clinics. Midwives were providers in 596 (58.8%)
      of these follow-up cases and clinicians in 417 (41.2%) cases. All PPIUD
      insertions by midwives were transvaginal and among them 43 (7.2%) had PPIUD
      related complications by the end of sixth week. These complications included 16
      (2.7%) cases of uterine infection, 14 (2.3%) IUD expulsions, 26 (4.4%) IUD
      removals, and 33 (5.5%) with overall method discontinuation. Only one case had
      uterine infection severe enough to warrant hospitalization. CONCLUSION: PPIUD
      insertion by trained midwives in Tanzania compares favorably with results
      reported from other settings.

PMID- 30225874
TI  - Institutionalizing postpartum family planning and postpartum intrauterine device
      services in Nepal: Role of training and mentorship.
AB  - OBJECTIVE: To explore the perceptions of key stakeholders on different modalities
      of training and mentoring activities for healthcare providers of postpartum
      family planning and postpartum intrauterine devices (PPFP/PPIUD). METHODS: In
      this qualitative study, data were collected from 40 participants in December 2017
      via focus group discussions (FGD) and in-depth interviews (IDI) in three
      hospitals implementing PPFP/PPIUD services and government line agencies in Nepal.
      Data were analyzed through content analysis and grouped into themes and
      categories. RESULTS: The majority of participants reported that PPFP/PPIUD
      training and mentoring was useful and contributed to their professional
      development. Most found that on-the-job training (OJT) was more effective than
      group-based training (GBT). CONCLUSION: Training and mentoring activities were
      perceived to be useful by health providers and OJT was the approach preferred by
      the majority. Further studies are necessary to explore the existing challenges
      and long-term effects of each modality of training and mentoring on health
      providers' competency and attitudes and on the uptake of PPIUD by postpartum
      mothers.

PMID- 30225876
TI  - Factors influencing the likelihood of acceptance of postpartum intrauterine
      devices across four countries: India, Nepal, Sri Lanka, and Tanzania.
AB  - OBJECTIVE: To examine the factors that positively influenced the likelihood of
      accepting provision of postpartum intrauterine devices (PPIUDs) across four
      countries: Sri Lanka, Nepal, Tanzania, and India. METHODS: Healthcare providers
      were trained across 24 facilities in counselling and insertion of PPIUDs as part
      of a large multicountry study. Women delivered were asked to take part in a 15
      minute face-to-face structured interview conducted by in-country data collection
      officers prior to discharge. Univariate analysis was performed to investigate
      factors associated with acceptance. RESULTS: From January 2016 to November 2017,
      6477 health providers were trained, 239 033 deliveries occurred, and 219 242
      interviews were conducted. Of those interviewed, 68% were counselled on family
      planning and 56% on PPIUD, with 20% consenting to PPIUD. Multiple counselling
      sessions was the only factor resulting in higher consent rates (OR 1.30-1.39)
      across all countries. Odds ratios for women's age, parity, and cadre of provider
      counselling varied between countries. CONCLUSION: Consent for contraception,
      specifically PPIUD, is such a culturally specific topic and generalization across
      countries is not possible. When planning contraceptive policy changes, it is
      important to have an understanding of the sociocultural factors at play.

PMID- 30225877
TI  - The impact of using nurses to perform postpartum intrauterine device insertions
      in Kalyani Hospital, India.
AB  - In the postpartum period women are vulnerable to unintended pregnancy, which may
      lead to legal or illegal abortion and impact on maternal and neonatal morbidity
      and mortality. Although several postpartum family planning options are available,
      lack of access to and availability of family planning services and trained staff
      pose serious challenges. Peripheral centers may not have a doctor; however, they
      will have nursing staff that can be trained to offer family planning counselling
      and services. The present study demonstrates how task sharing with nurses to
      provide postpartum intrauterine device (PPIUD) services worked to give women a
      convenient and safe contraceptive method. PPIUD insertion provides women the
      additional advantage of leaving hospital with appropriate long-term contraception
      after institutional delivery, and also decreases the costs borne by patients and
      the government. This approach also impacts maternal and newborn health by
      avoiding unwanted pregnancy.

PMID- 30225878
TI  - The frailty syndrome and outcomes in the TOPCAT trial.
AB  - AIMS: The impact of frailty on outcomes in randomized heart failure with
      preserved ejection fraction (HFpEF) trials has not been previously reported. This
      analysis sought to characterize frailty in a large contemporary HFpEF clinical
      trial cohort and to evaluate its impact on patient relevant outcomes. METHODS AND
      RESULTS: Using data from the Treatment of Preserved Cardiac Function Heart
      Failure with an Aldosterone Antagonist (TOPCAT) trial, a frailty index (FI) was
      constructed at baseline using 39 clinical, laboratory, and self-reported
      variables. The relationship between frailty and outcomes and the role of frailty
      in modulating the benefits of spironolactone were examined in a subset of 1767
      TOPCAT patients. For the cohort as a whole (mean age 71.5 years, 49% female), the
      mean FI at baseline was 0.37 +/- 0.11. Four frailty classes were defined ranging
      from FI < 0.3 to FI >= 0.5. Overall, 94% of subjects were considered frail
      (defined as a FI > 0.21). Mean age was lowest for the most frail class (69 +/- 9
      years for Class 4; 73 +/- 10 years for Class 1; P < 0.001). Body mass index,
      systolic blood pressure, and pulse pressure all increased as FI increased. Both
      primary and secondary outcomes increased as frailty severity increased. There was
      no interaction between frailty class and treatment effect of spironolactone.
      CONCLUSIONS: Frailty was very common in TOPCAT HFpEF participants. Greater
      frailty was associated with a higher risk of cardiovascular outcomes and
      mortality. The benefit of spironolactone on outcomes in TOPCAT was not attenuated
      by frailty class.

PMID- 30225879
TI  - Simplified apical four-chamber view evaluation of relative apical sparing of
      longitudinal strain in diagnosing AL amyloid cardiomyopathy.
AB  - AIM OF THE STUDY: To assess the diagnostic utility of a simplified approach to
      relative apical sparing of longitudinal strain (RAS LS) using only an apical four
      chamber view (A4C) in patients with AL amyloid cardiomyopathy (ALAC). METHODS: We
      retrospectively evaluated echocardiographic recordings of 20 patients with ALAC,
      20 patients with Fabry disease-related cardiomyopathy (FD), and 20 patients with
      concentric hypertensive left ventricular hypertrophy (HLVH) matched for mean LV
      mean thickness. Peak segmental LS values of the interventricular septum and
      lateral LV wall were measured in the A4C using two-dimensional speckle-tracking
      echocardiography. RAS LS was calculated as average apical LS/(average basal LS +
      average midventricular LS). RESULTS: Relative apical sparing of longitudinal
      strain values in patients with ALAC (1.23 +/- 0.64) were significantly higher
      than those in FD patients (0.75 +/- 0.19, P < 0.05) as well as in individuals
      with HLVH (0.75 +/- 0.23, P < 0.05), but with a significant overlap. The optimal
      RAS LS value differentiating ALAC from FD and HLVH with 70% sensitivity and 75%
      specificity was 0.88 (AUC 0.79). In multivariate modeling, RAS LS was
      significantly additive to traditional predictors of ALAC (low QRS voltage and
      pseudoinfarct ECG patterns, pericardial effusion, E/e' ratio, E-wave deceleration
      time; P < 0.05 for all models). CONCLUSIONS: Simplified RAS LS evaluation
      represents an attractive approach for diagnostics of ALAC. However, because of
      considerable overlap with other disorders with hypertrophic phenotype, the
      analysis of RAS LS in the A4C should be combined with other traditional
      echocardiographic and ECG predictors in differentiating ALAC from other forms of
      concentric LV wall thickening.

PMID- 30225880
TI  - Delivering remote monitoring data to patients with implantable cardioverter
      defibrillators: Does medium matter?
AB  - BACKGROUND: This study presents findings on the impact of providing patients with
      their implantable device data on patients' satisfaction, engagement, healthcare
      utilization, and provider's perceptions of this practice. Remote monitoring of
      implantable cardioverter defibrillators (ICDs) improves patient care through
      timely delivery of ICD data to the clinic. However, patients usually do not
      receive their ICD data. Providers are concerned that messaging patients with
      their device data could increase clinical workload. METHODS: To evaluate the
      impact of sharing ICD data summary through the patient portal, 128 patients were
      randomized into two groups. Group A and B received their data through the patient
      portal and postal mail, respectively. Data were collected through surveys and
      medical record reviews. Forty-eight providers also completed a survey. RESULTS:
      At the end of the study, at least two-thirds of patients were satisfied with the
      amount of information received through the electronic or paper ICD data summary.
      Additionally, providing patients with their device data did not increase ICD
      specific clinical workload (e.g., calls or messages to provider). While providers
      did not foresee the provision of ICD data to patients as decreasing or improving
      clinical workload, they did see potential value in it for patients. CONCLUSIONS:
      Providing patients with their ICD data (through paper or electronic means) might
      have the potential to improve patient satisfaction and enhance shared-decision
      making without adversely impacting clinical workload.

PMID- 30225881
TI  - Increased residual cardiovascular risk in patients with diabetes and high versus
      normal triglycerides despite statin-controlled LDL cholesterol.
AB  - AIM: To determine whether high triglycerides (TG) in the presence of statin
      controlled LDL-C influence the risk of cardiovascular disease (CVD) among
      patients with diabetes in real-world clinical practice. MATERIALS AND METHODS: We
      identified adults with diabetes from the Southern California and Pacific
      Northwest regions of Kaiser Permanente. We included patients undergoing statin
      therapy with LDL-C from 40-100 mg/dL who were not undergoing other lipid-lowering
      therapies and had a prior diagnosis of atherosclerotic CVD or at least one other
      CVD risk factor. We grouped patients into high TG (200-499 mg/dL; n = 5542) or
      normal TG (<150 mg/dL, n = 22 411) from January 2010 through December 2016 to
      compare incidence rates and rate ratios of first non-fatal myocardial infarction
      (MI), non-fatal stroke, unstable angina and coronary revascularization. We
      adjusted multivariable analyses for age, sex, race/ethnicity, smoking status,
      blood pressure, HbA1c, serum creatinine, presence of ischaemic heart disease and
      study site. RESULTS: Adjusted rate ratios for the four outcomes were all
      statistically significantly different. The incidence rate for non-fatal MI was
      30% higher in the high TG group (rate ratio, 1.30; 95% CI, 1.08-1.58; P = 0.006).
      The rate was 23% higher for non-fatal stroke (1.23, 1.01-1.49, P = 0.037), 21%
      higher for coronary revascularization (rate ratio, 1.21; 95% CI, 1.02-1.43; P =
      0.027) and was, non-significantly, 33% higher for unstable angina (rate ratio,
      1.33; 95% CI, 0.87-2.03; P = 0.185). CONCLUSIONS: Despite statin-controlled LDL-C
      levels, CV events were greater among patients with diabetes and high TG levels.
      Because we controlled for cardiometabolic risk factors, it is likely that the
      difference in TG levels contributed to the excess risk observed in patients with
      high TGs.

PMID- 30225882
TI  - Rationale and design of the phase 2b clinical trials to study the effects of the
      partial adenosine A1-receptor agonist neladenoson bialanate in patients with
      chronic heart failure with reduced (PANTHEON) and preserved (PANACHE) ejection
      fraction.
AB  - Despite major advances in the treatment of chronic heart failure (HF) with
      reduced ejection fraction (HFrEF), morbidity and mortality associated with the
      condition remain high, suggesting the need for additional treatment options,
      particularly haemodynamically neutral treatments that do not alter blood
      pressure, heart rate, or renal function. HF with preserved ejection fraction
      (HFpEF) is also associated with high morbidity and mortality and adequate
      treatment options are limited; thus there is a critical unmet need for the
      development of novel therapies for HFpEF. Chronic HFrEF and HFpEF are both
      systemic disorders that affect not only the heart but several other tissues and
      organs including skeletal muscle, leading to exercise intolerance and dyspnoea.
      Partial adenosine A1-receptor agonists represent a novel potential therapy for HF
      regardless of underlying ejection fraction given their minimal effect on heart
      rate and blood pressure, and preclinical data demonstrate several possible
      beneficial mechanisms, including improved mitochondrial function and sarcoplasmic
      reticulum Ca2+ -ATPase (SERCA2a) activity, enhanced energy substrate utilization,
      reverse ventricular remodelling, and anti-ischemic, cardioprotective properties.
      However, data on this class of drugs in humans are scarce, and the optimal dose
      of the partial adenosine A1 receptor, neladenoson bialanate, has not been
      defined. Here we describe the design and rationale of two randomized, double
      blind, placebo-controlled, parallel-group, dose-finding phase 2b trials, PANTHEON
      (HFrEF) and PANACHE (HFpEF), that will advance our understanding of the potential
      benefit and optimal dose of neladenoson bialanate and provide critical
      information for the planning of future phase 3 trials.

PMID- 30225883
TI  - Resistance mechanism of the oncogenic beta3-alphaC deletion mutation in BRAF
      kinase to dabrafenib and vemurafenib revealed by molecular dynamics simulations
      and binding free energy calculations.
AB  - BRAF kinase is an essential target for anti-cancer drug development. Emergence of
      the beta3-alphaC loop deletion mutation (DeltaNVTAP) in BRAF kinase frequently
      occurred in human cancers seriously compromises the therapeutic efficacy of some
      BRAF kinase inhibitors, such as dabrafenib and vemurafenib. However, the
      mechanism of this resistance is still not well understood. In this study, the
      influence of the beta3-alphaC deletion mutation on the binding profiles of three
      BRAF kinase inhibitors (AZ628, dabrafenib, and vemurafenib) with BRAFV600E or
      BRAFDeltaNVTAP was explored by conventional molecular dynamics (MD) simulations
      and binding free energy calculations. The simulation results indicated that the
      beta3-alphaC deletion mutation enhances the flexibility of the alphaC helix and
      alters their conformations, which amplify the conformational entropy change (
      TDeltaS) and weaken the interactions between the inhibitors and BRAF. The further
      per-residue binding free energy decomposition analysis revealed that the
      DeltaNVTAP mutation changed the contributions of a few key residues to the
      bindings of dabrafenib or vemurafenib, such as L57, L66, W83, C84, F135, G145,
      and F147, but did not have obvious impact on the contributions of these residues
      to AZ628. Our results provide valuable clues to understand the mechanisms of drug
      resistance conferred by the beta3-alphaC deletion mutation.

PMID- 30225884
TI  - The epicardial adipose inflammatory triad: coronary atherosclerosis, atrial
      fibrillation, and heart failure with a preserved ejection fraction.

PMID- 30225885
TI  - Body uneasiness is associated with food addiction symptoms: A cross-sectional
      study.
AB  - The main aim of the present study was to investigate the association between food
      addiction (FA) symptoms and body uneasiness in a nonclinical sample, while
      controlling for potential confounding variables. Participants (N = 395; 123 men)
      were administered self-report measures assessing FA, binge eating severity, body
      uneasiness, depressive symptoms, emotion dysregulation and socio-demographic
      variables. Body uneasiness was independently associated with FA symptoms
      (standardized beta coefficients ranging between 0.41 [p < 0.001] and 0.22 [p <
      0.001]), even when controlling for the presence of other variables. This finding
      suggests that body uneasiness may be a crucial symptom in the development and/or
      maintenance of FA symptoms.

PMID- 30225886
TI  - Relationship Between Leptin Level, Inflammation, and Volume Status in Maintenance
      Hemodialysis Patients.
AB  - Maintenance hemodialysis (HD) patients often experience fluctuations of volume
      status. Although hypervolemia possibly induces systemic inflammation, the
      relationship between volume status and leptin has not yet been well defined. The
      aims of this study were to determine the levels of leptin, C-reactive protein
      (CRP), and ferritin in relation to volume status and to assess the relationship
      between leptin and volume and inflammatory status in chronic HD patients. This
      prospective study included 93 HD patients divided, based on evaluation using the
      body composition monitor, into normovolemic and hypervolemic groups
      (overhydration/extracellular water [OH/ECW] <= 15% and OH/ECW > 15%,
      respectively). The levels of leptin and inflammatory markers (CRP, ferritin) were
      determined during a mid-week dialysis session in all patients. There were more
      hypervolemic patients after 12 months of follow up than at baseline (41% vs.
      38%). Hypervolemic patients had significantly lower leptin levels (11.42 +/-
      19.24 ng/mL vs. 34.53 +/- 40.32 ng/mL at baseline and 13.41 +/- 22.04 ng/mL vs.
      41.54 +/- 21.78 ng/mL at 12 months), longer time on dialysis, and poorer
      nutritional status than normovolemic patients. Inflammation was present
      regardless of the volume status, but hypervolemic patients had significantly
      higher CRP and ferritin than normovolemic patients. A statistically significant
      reverse correlation was found between leptin level, hyperhydration index, and
      OH/ECW. No significant correlation was found between leptin and inflammatory
      markers CRP and ferritin.

PMID- 30225887
TI  - Extracorporeal membrane oxygenation retrieval factors and survival to intensive
      care unit discharge.
AB  - OBJECTIVE: Audit of extracorporeal membrane oxygenation (ECMO) retrieval service
      operating in Victoria, Australia, regarding retrieval factors and patient
      survival to intensive care unit (ICU) discharge. METHODS: Retrospective cohort
      analysis of Adult Retrieval Victoria ECMO retrievals with subsequent ICU
      admission (n = 88) from January 2014 to December 2017. RESULTS: Complications
      occurring during veno-arterial ECMO transfer have significant association with
      decreased survival to ICU discharge (P = 0.012). Mortality for veno-arterial ECMO
      patients was greater than veno-venous ECMO patients. CONCLUSION: Retrieval ECMO
      achieves similar survival outcomes to in-house ECMO. The demonstrated
      relationship of adverse events during retrieval phase to subsequent mortality in
      ICU highlights the need for optimised case management and retrieval processes.

PMID- 30225888
TI  - The relationship between the claustrum and endopiriform nucleus: A perspective
      towards consensus on cross-species homology.
AB  - With the emergence of interest in studying the claustrum, a recent special issue
      of the Journal of Comparative Neurology dedicated to the claustrum (Volume 525,
      Issue 6, pp. 1313-1513) brought to light questions concerning the relationship
      between the claustrum (CLA) and a region immediately ventral known as the
      endopiriform nucleus (En). These structures have been identified as separate
      entities in rodents but appear as a single continuous structure in primates.
      During the recent Society for Claustrum Research meeting, a panel of experts
      presented data pertaining to the relationship of these regions and held a
      discussion on whether the CLA and En should be considered (a) separate unrelated
      structures, (b) separate nuclei within the same formation, or (c) subregions of a
      continuous structure. This review article summarizes that discussion, presenting
      comparisons of the cytoarchitecture, neurochemical profiles, genetic markers, and
      anatomical connectivity of the CLA and En across several mammalian species. In
      rodents, we conclude that the CLA and the dorsal endopiriform nucleus (DEn) are
      subregions of a larger complex, which likely performs analogous computations and
      exert similar effects on their respective cortical targets (e.g., sensorimotor
      versus limbic). Moving forward, we recommend that the field retain the
      nomenclature currently employed for this region but should continue to examine
      the delineation of these structures across different species. Using thorough
      descriptions of a variety of anatomical features, this review offers a clear
      definition of the CLA and En in rodents, which provides a framework for
      identifying homologous structures in primates.

PMID- 30225889
TI  - Paraoxonase 1 (PON1) attenuates sperm hyperactivity and spontaneous acrosome
      reaction.
AB  - BACKGROUND: Sperm capacitation is essential for proper fertilization and is
      associated with increased sperm hyperactivity (HA) and acrosome reaction (AR).
      For successful fertilization, AR timing is critical; accordingly, early
      spontaneous AR may not facilitate fertilization. Paraoxonase 1 (PON1) possesses
      antioxidant properties which affect sperm capacitation. The association between
      PON1, semen parameters, and capacitation is not fully understood. OBJECTIVE: To
      study PON1 activity in relation to human sperm hyperactivity and AR. MATERIALS
      AND METHODS: Semen samples were collected, and parameters were determined
      (volume, concentration, total sperm count, percentage total motility, and
      percentage normal morphology) according to World Health Organization (WHO)
      guidelines. AR and hyperactivity were evaluated using FITC-PSA, staining, and
      computer-aided sperm analysis (CASA). PON1 activity was assessed using
      arylesterase activity assay. RESULTS: Purified PON1 inhibited both sperm
      hyperactivity and AR in a dose-dependent manner. Native semen PON1 activity was
      positively associated with higher sperm concentration and negatively associated
      with spontaneous acrosome reaction (sAR). DISCUSSION AND CONCLUSION: PON1 may
      have a positive effect on fertility via its ability to prevent early spontaneous
      sperm capacitation and AR before reaching the female genital tract.

PMID- 30225890
TI  - Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of
      evolocumab between Caucasian and Asian populations.
AB  - AIMS: To evaluate the potential ethnic differences in the pharmacokinetics (PK)
      and pharmacodynamics (PD) of evolocumab in Caucasian and Asian populations using
      population PK/PD modelling analysis. METHODS: Data from different ethnic groups
      in 5 Phase I clinical trials, including two American studies, one Japanese study
      and two Chinese studies, were chosen for model building and evaluation. A target
      mediated drug disposition model together with an indirect response model best
      captured evolocumab binding and the removal of unbound proprotein convertase
      subtilisin/kexin type 9 (PCSK9) as well as a reduction in circulating low-density
      lipoprotein cholesterol (LDL-C). Ethnicity and other related factors (body
      weight, target expression level etc.) were analysed as potential covariates.
      RESULTS: The estimated linear clearance and volume of evolocumab were 0.24 l day
      1 and 2.75 l, respectively, which was consistent with the previous modelling
      results from the American trials. The time course of the LDL-C reduction was
      described by an indirect response model with the elimination rate of LDL-C being
      modulated by unbound PCSK9. The concentration of unbound PCSK9 associated with
      the half-maximal inhibition of LDL-C elimination was 1.28 nmol l-1 . Both the PK
      and PD characteristics were consistent between the Caucasian and Asian
      populations. CONCLUSION: The target-mediated drug disposition model successfully
      described the PK and PD characteristics of evolocumab, and this analysis found no
      significant differences in the PK/PD relationship for its LDL-C lowering effects
      between Caucasians and Asians.

PMID- 30225891
TI  - Reply: Surprisingly low incidence of left ventricular thrombosis in anterior ST
      segment elevation myocardial infarction.

PMID- 30225892
TI  - Interaction of Dasabuvir With Clopidogrel: Did Predictions by Physiologically
      Based Pharmacokinetics Modeling Pass the Test?

PMID- 30225893
TI  - Effects of the short-term exposure to ambient air pollution on atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is an important arrhythmia associated with
      cardiovascular morbidity and mortality. This study is focused on exploring the
      potential relationship between short-term air pollution exposure and occurrence
      of AF. METHODS: A case-crossover design was used to investigate the effect of
      pollutants on AF occurrence among 100 patients from 2013 to 2014. The air
      pollutants included ambient particulate matter less than 2.5 MUm in aerodynamic
      diameter (PM2.5 ), particulate matter less than 10 MUm in aerodynamic diameter
      (PM10 ), nitrogen dioxide (NO2 ), sulfur dioxide (SO2 ), carbon monoxide (CO),
      and ozone (O3 ). Participants with cardiac implantable electronic devices
      implanted were followed-up to December 31, 2014. RESULTS: A 10 MUg/m3 increase of
      PM2.5 and PM10 was associated with 3.8% (95% confidence interval [CI]: 1.4-6.2)
      and 2.7% (95% CI: 0.6-4.8) increase in the risk of AF occurrence, respectively.
      No statistically significant association was noted with SO2 , NO2 , CO, and O3 .
      CONCLUSIONS: Short-term exposure to particular matter, both PM2.5 and PM10 , is
      associated with an increased risk of AF. This further demonstrates the urgency
      for air quality monitoring and control in geographical area with intense
      pollution.

PMID- 30225894
TI  - Strategies Towards Capturing Nitrogenase Substrates and Intermediates via
      Controlled Alteration of Electron Fluxes.
AB  - Nitrogenase utilizes an ATP-dependent reductase to deliver electrons to its
      catalytic component to enable two important reactions: the reduction of N2 to NH4
      + , and the reduction of CO to hydrocarbons. The two nitrogenase-based reactions
      parallel the industrial Haber-Bosch and Fischer-Tropsch processes, yet they occur
      under ambient conditions. As such, understanding the enzymatic mechanism of
      nitrogenase is crucial for the future development of biomimetic strategies for
      energy-efficient production of valuable chemical commodities. Mechanistic
      investigations of nitrogenase has long been hampered by the difficulty to trap
      substrates and intermediates relevant to the nitrogenase reactions. Recently, we
      have successfully captured CO on the Azotobacter vinelandii V-nitrogenase via two
      approaches that alter the electron fluxes in a controlled manner: one approach
      utilizes an artificial electron donor to trap CO on the catalytic component of V
      nitrogenase in the resting state; whereas the other employs a mismatched
      reductase component to reduce the electron flux through the system and
      consequently accumulate CO on the catalytic component of V-nitrogenase. Here we
      summarize the major outcome of these recent studies, which not only clarified the
      catalytic relevance of the one-CO (lo-CO) and multi-CO (hi-CO) bound states of
      nitrogenase, but also pointed to a potential competition between N2 and CO for
      binding to the same pair of reactive Fe sites across the sulfur belt of the
      cofactor. Together, these results highlight the utility of these strategies in
      poising the cofactor at a well-defined state for substrate- or intermediate
      trapping via controlled alteration of electron fluxes, which could prove
      beneficial for further elucidation of the mechanistic details of nitrogenase
      catalyzed reactions.

PMID- 30225895
TI  - Sexual dysfunction and phobic anxiety in breast cancer survivors.

PMID- 30225896
TI  - Tolerability of iobitridol in patients with non-immediate hypersensitivity
      reactions to iodinated contrast media.

PMID- 30225897
TI  - The genetics of phenotypic plasticity. XVI. Interactions among traits and the
      flow of information.
AB  - Although the environment varies, adaptive trait plasticity is uncommon, which can
      be due to either costs or limitations. Currently there is little evidence for
      costs of plasticity; limitations are a more promising explanation, including
      information reliability. A possible cause for a decrease in information
      reliability is the channeling of environmental information through one trait that
      then affects the phenotype of a second trait, the information path. Using an
      individual-based simulation model, I explored the ways in which configurations of
      trait interactions and patterns of environmental variation in space and time
      affect the evolution of phenotypic plasticity. I found that genotypes and
      phenotypes evolved to shorten and simplify the information path from the
      environment to fitness. A shortened path was characterized by a decrease in the
      amount of plasticity for traits that had a less direct connection between the
      environment of development and fitness. A simplified path was characterized by a
      decrease in the amount of plasticity for traits that had multiple paths between
      the environment and their phenotype. These results suggest that an eighth
      proposition be added to the theory of the evolution of phenotypic plasticity:
      Trait plasticity will evolve to minimize the information path between the
      environment and fitness.

PMID- 30225898
TI  - Association of electroconvulsive therapy with psychiatric readmissions in
      Singapore tertiary mood disorder unit.

PMID- 30225899
TI  - Chalcogen Bonding: An Overview.
AB  - In the last few decades, "unusual" noncovalent interactions like anion-pi and
      halogen bonding have emerged as interesting alternatives to the ubiquitous
      hydrogen bonding in many research areas. This is also true, to a somewhat lesser
      extent, for chalcogen bonding, the noncovalent interaction involving Lewis acidic
      chalcogen centers. Herein, we aim to provide an overview on the use of chalcogen
      bonding in crystal engineering and in solution, with a focus on the recent
      developments concerning intermolecular chalcogen bonding in solution-phase
      applications. In the solid phase, chalcogen bonding has been used for the
      construction of nano-sized structures and the self-assembly of sophisticated self
      complementary arrays. In solution, until very recently applications mostly
      focused on intramolecular interactions which stabilized the conformation of
      intermediates or reagents. In the last few years, intermolecular chalcogen
      bonding has increasingly also been exploited in solution, most notably in anion
      recognition and transport as well as in organic synthesis and organocatalysis.

PMID- 30225900
TI  - Positive effect of progesterone on motility and velocity of fresh, vitrified
      without permeable cryoprotectants and frozen with permeable cryoprotectants human
      spermatozoa.
AB  - Steroid hormone progesterone has been found to play an important role in the
      migration of spermatozoa through the reproductive tract, as well as to induce
      hyperactive motility and increase sperm velocity. The aim of this study was to
      examine whether progesterone could induce beneficial effects in vitrified and
      slow-frozen spermatozoa. During the research process, 50 semen samples were
      divided into three treatment groups; noncryopreserved, slow-freezing and
      vitrification. After thawing and an incubation period of 2 hr to induce
      capacitation, semen samples from each treatment group were treated with 50 nM, 25
      nM progesterone and a control solution for 30 min. Thereafter, the sperm
      suspensions were examined manually to assess the proportion of viable and motile
      spermatozoa, as well as using the CASA to evaluate the velocity parameters. The
      results indicated a higher proportion of progressively motile spermatozoa in
      vitrified teratozoospermic samples and improved velocity parameters in slow
      frozen normozoospermic and teratozoospermic samples. The main conclusion of this
      research was that the used progesterone concentration of 50 nM was sufficient to
      significantly improve the motility of vitrified teratozoospermic samples and
      velocity parameters of cryopreserved sperm samples. The present findings might
      have important implications in determining ways of improving the current low
      rates of motility in cryopreserved spermatozoa.

PMID- 30225901
TI  - Sudden cardiac arrest in end-stage renal disease patients on dialysis: A
      nationwide study.
AB  - BACKGROUND: Sudden cardiac arrest (SCA) is frequently encountered in end-stage
      renal disease (ESRD) patients on dialysis. There is a dearth of national data on
      SCA-associated outcomes in this specific patient population. The aim of the
      present study is to study these parameters from a nationally representative US
      population. METHODS: Data were extracted from National Inpatient Sample database
      from October 2005 to December 2014. All patients with clinical encounter of
      dialysis during the study period were enrolled. Patients who underwent SCA,
      ventricular fibrillation, ventricular tachycardia, and ventricular flutter were
      then identified by applying relevant International Classification of Diseases,
      Ninth Revision, Clinical Modification codes. Patients with acute kidney injury
      and prior renal transplant were excluded. Propensity matching was done to balance
      covariates among study groups. Logistic regression analysis was done to assess
      for predictors of SCA-associated mortality in ESRD patients on dialysis. RESULTS:
      A total of 1 147 760 patients were included in the final analyses. Patients who
      suffered SCA were older when compared to the non-SCA cohort and had a higher
      burden of comorbidities. About half (52.10%) of ESRD patients who suffered SCA
      died. Advanced age, metabolic acidosis, and cardiogenic shock were independently
      associated with reduced survival after SCA. New implantable cardioverter
      defibrillator implantation continues to be low in this patient population at
      discharge. CONCLUSION: SCA in settings of ESRD on dialysis carries high mortality
      and frequent morbidity. Further research in therapeutic interventions that could
      prevent SCA in this vulnerable population is utmost needed.

PMID- 30225902
TI  - Peripheral apelin mediates stress-induced alterations in gastrointestinal motor
      functions depending on the nutritional status.
AB  - Exposure to stress induces gastrointestinal (GI) dysmotility. In rodents, acute
      restraint stress (ARS) inhibits gastric emptying (GE) and intestinal transit (IT)
      via central and peripheral corticotropin-releasing factor (CRF)-mediated
      pathways. Peripherally administered apelin-13 was shown to inhibit GI motor
      functions; moreover, stress-induced upregulation of gastric apelin content was
      demonstrated in rats suggesting that peripheral apelin may mediate stress-induced
      alterations in GI motility. We investigated the role of endogenous peripheral
      apelin in stress-induced GI dysfunction. GE, IT and gastro-duodenal fasting
      motility were measured in non-stressed (NS), CRF-injected and ARS-loaded rats.
      CRF and apelin receptor antagonists astressin or F13A was administered before ARS
      or peripheral CRF injection. Apelin and APJ receptor expressions were determined
      using immunohistochemistry and quantified by qRT-PCR. Double immunofluorescence
      was performed for enteric neuronal apelin. GE and IT were delayed by CRF and ARS.
      ARS-induced changes were attenuated by F13A, whereas astressin was ineffective.
      CRF-induced alterations in GE and IT were restored completely by astressin, while
      they were diminished by F13A. Antral phase III-like contractions were disturbed
      following ARS which were preserved by preadministration of astressin, but not
      F13A. CRF impaired gastric and duodenal fasting contractions, while these changes
      were not altered by F13A. ARS increased apelin expression in stomach and
      duodenum. Apelin immunoreactivity was detected in mucosa, smooth muscles and
      myenteric plexi, whereas dense APJ receptor expression was observed within tunica
      muscularis. APJ receptor was downregulated in rats fasted overnight. These
      results suggest that enteric apelin acts as an inhibitor stress mediator in the
      postprandial state.

PMID- 30225903
TI  - Comparison of novel dual mode vs conventional single pass of a 1450-nm diode
      laser in the treatment of acne vulgaris for Korean patients: A 20-week
      prospective, randomized, split-face study.
AB  - BACKGROUND: Although a 1450-nm diode laser has been shown to be effective for
      acne, the conventional high-energy stamp-only regimen is often associated with
      pain and hyperpigmentation, especially for dark-skinned individuals. AIMS: To
      evaluate whether the novel dual regimen has clinical advantages for acne
      treatments compared with conventional regimen in Asian patients. PATIENTS AND
      METHODS: Twenty-four Korean patients with facial acne were treated with a 1450-nm
      diode laser through a 20-week, randomized, split-face study. The patients were
      treated with three consecutive sessions at 4-week intervals. One half of the face
      received a dual regimen consisting of low-fluence stamping mode (5-6 J/cm2 ) for
      inflammatory acne lesions only, followed by 4-5 passes of moving mode for the
      full face. The other side received a single-pass treatment of conventional high
      fluence stamp mode (14-15 J/cm2 ). Evaluations for acne, sebum secretion
      measurements, and safety profiles were performed. RESULTS: At the final 12-week
      follow-up evaluations, the dual-mode side demonstrated better improvements in
      both inflammatory and noninflammatory lesion counts, acne severity assessments,
      and reduction in sebum secretion compared with stamp-only side. Subjective
      satisfaction for the improvement for acne, seborrhea, and texture correlated well
      with objective assessments. In addition, degrees of pain and treatment-related
      side effects were remarkably decreased in the novel dual mode. CONCLUSION: This
      novel dual regimen of the 1450-nm laser demonstrated improved efficacies for acne
      and seborrhea with satisfactory safety profiles. Therefore, this regimen would be
      a viable option for acne treatments either as monotherapy or as combination
      therapy.

PMID- 30225904
TI  - Thirty-day hospital readmission rate amongst older adults correlates with an
      increased number of medications, but not with Beers medications.
AB  - AIM: We sought to explore the relationship between the number of medications at
      hospital discharge and 30-day rehospitalization in older adults aged >65 years.
      METHODS: This was a multicenter cohort study to determine whether an increased
      number of medications was associated with 30-day rehospitalization in patients
      aged >65 years. We explored the relationship between rehospitalization and other
      risk factors. Data were collected from a large health system in the New York
      metropolitan area from September 2011 to January 2013. The primary outcome was 30
      day hospital readmission from the index hospitalization. RESULTS: Patients had a
      mean +/- SD age of 78 +/- 9 years; 55% were women. The average length of stay
      after discharge from the hospital was 6 days. An increased number of medications
      was significantly associated with unplanned 30-day hospital readmission (P <
      0.05). For each medication, the risk of rehospitalization increased by 4% (OR
      1.04, 95% CI 1.03, 1.05). Patients discharged to rehabilitation centers were 32%
      more likely to be readmitted than patients discharged home (OR 1.39, 95% CI 1.27
      1.51). Other risk factors significantly associated with 30-day rehospitalization
      were: cancer, intensive care unit, chronic heart failure, renal diseases and
      peripheral vascular diseases. Hypertension was negatively associated with 30-day
      unplanned rehospitalization (OR 0.88, 95% CI 0.82-0.95). No significant
      association between the number of Beers medications and 30-day rehospitalization
      was observed, after controlling for the number of medications and other
      covariates. CONCLUSIONS: The number of discharge medications was significantly
      associated with 30-day hospital readmission among older adult patients. Important
      risk factors for 30-day rehospitalization were discharge location, cancer,
      intensive care unit, chronic heart failure, renal diseases and peripheral
      vascular diseases. Geriatr Gerontol Int 2018; 18: 1513-1518.

PMID- 30225905
TI  - Frequency of mood and anxiety fluctuations in Parkinson's disease patients with
      motor fluctuations: A systematic review.
AB  - After 5 years of treatment with levodopa, approximately 40% to 50% of patients
      with Parkinson's disease (PD) develop motor complications such as dyskinesias or
      motor fluctuations. These are often accompanied by nonmotor fluctuations, such as
      fluctuations in mood symptoms. The aim of this systematic review is to assess the
      frequency of such mood fluctuations in PD patients with motor fluctuations and to
      explore the association between these mood fluctuations and motor fluctuations.
      We performed a systematic literature search in PubMed, Medline, and the Cochrane
      Library. This search yielded 10 studies, of which 9 were included after quality
      assessment. The frequency of anxiety fluctuations in PD patients with motor
      fluctuations ranged from 3.1% to 67.7% with a weighted mean of 35.4%. The
      frequency of fluctuations in depressive symptoms ranged from 2.1% to 71.4%, with
      a weighted mean of 34.9%. The frequency of fluctuations in symptoms of panic
      ranged from 3.1% to 54.5%, with a weighted mean of 37.1%. Symptoms of anxiety and
      depression are mostly present in the "off" state. We conclude that mood
      fluctuations occur frequently in PD patients with motor fluctuations. The
      methodology used to assess mood fluctuation varies widely and there is a lack of
      a generally accepted assessment procedure for fluctuating symptoms. Research
      would benefit from a more uniform approach to assessment of nonmotor
      fluctuations. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 30225906
TI  - Expression analysis of limb element markers during mouse embryonic development.
AB  - BACKGROUND: While data regarding expression of limb element and tissue markers
      during normal mouse limb development exist, few studies show expression patterns
      in upper and lower limbs throughout key limb development stages. A comparison to
      normal developmental events is essential when analyzing development of the limb
      in mutant mice models. RESULTS: Expression patterns of the joint marker Gdf5,
      tendon and ligament marker Scleraxis, early muscle marker MyoD1, and blood vessel
      marker Cadherin5 (Cdh5) are presented during the most active phases of embryonic
      mouse limb patterning. Anti-neurofilament staining of developing nerves in the
      fore- and hindlimbs and cartilage formation and progression also are described.
      CONCLUSIONS: This study demonstrates and describes a range of key morphological
      markers and methods that together can be used to assess normal and abnormal limb
      development. Developmental Dynamics 247:1217-1226, 2018. (c) 2018 The Authors.
      Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American
      Association of Anatomists.

PMID- 30225907
TI  - Transcatheter aortic valve replacement: The year in review 2017.
AB  - This article is a continuation of our previously published annual reviews of
      transcatheter aortic valve replacement (TAVR). In 2017, TAVR further established
      a foothold in the management of intermediate risk patients with the publication
      of SURTAVI trial. Randomized trials also addressed the use of cerebral protection
      during TAVR and single versus dual antiplatelet therapy after TAVR. Newer
      generation valve systems continued to be studied for their efficacy and safety.
      This paper summarizes the major studies published in 2017.

PMID- 30225908
TI  - Adolescent pregnancy at antiretroviral therapy (ART) initiation: a critical
      barrier to retention on ART.
AB  - INTRODUCTION: Adolescence and pregnancy are potential risk factors for loss to
      follow-up (LTFU) while on antiretroviral therapy (ART). We compared adolescent
      and adult LTFU after ART initiation to quantify the impact of age, pregnancy, and
      site-level factors on LTFU. METHODS: We used routine clinical data for patients
      initiating ART as young adolescents (YA; 10 to 14 years), older adolescents (OA;
      15 to 19 years) and adults (>=20 years) from 2000 to 2014 at 52 health facilities
      affiliated with the International epidemiology Databases to Evaluate AIDS (IeDEA)
      East Africa collaboration. We estimated cumulative incidence (95% confidence
      interval, CI) of LTFU (no clinic visit for >=6 months after ART initiation) and
      identified patient and site-level correlates of LTFU, using multivariable Cox
      proportional hazards models for all patients as well as individual age groups.
      RESULTS: A total of 138,387 patients initiated ART, including 2496 YA, 2955 OA
      and 132,936 adults. Of these, 55%, 78% and 66%, respectively, were female and
      0.7% of YA, 22.3% of OA and 8.3% of adults were pregnant at ART initiation.
      Cumulative incidence of LTFU at five years was 26.6% (24.6 to 28.6) among YA,
      44.1% (41.8 to 46.3) among OA and 29.3% (29.1 to 29.6) among adults. Overall,
      compared to adults, the adjusted hazard ratio, aHR, (95% CI) of LTFU for OA was
      1.54 (1.41 to 1.68) and 0.77 (0.69 to 0.86) for YA. Compared to males, pregnant
      females had higher hazard of LTFU, aHR 1.20 (1.14 to 1.27), and nonpregnant women
      had lower hazard aHR 0.90 (0.88 to 0.93). LTFU hazard among the OA was primarily
      driven by both pregnant and nonpregnant females, aHR 2.42 (1.98 to 2.95) and 1.51
      (1.27 to 1.80), respectively, compared to men. The LTFU hazard ratio varied by
      IeDEA program. Site-level factors associated with overall lower LTFU hazard
      included receiving care in tertiary versus primary-care clinics aHR 0.61 (0.56 to
      0.67), integrated adult and adolescent services and food ration provision aHR
      0.93 (0.89 to 0.97) versus nonintegrated clinics with food ration provision,
      having patient support groups aHR 0.77 (0.66 to 0.90) and group adherence
      counselling aHR 0.61 (0.57 to 0.67). CONCLUSIONS: Older adolescents experienced
      higher risk of LTFU compared to YA and adults. Interventions to prevent LTFU
      among older adolescents are critically needed, particularly for female and/or
      pregnant adolescents.

PMID- 30225909
TI  - Cathode Material Determines Product Selectivity for Electrochemical C-H
      Functionalization of Biaryl Ketoximes.
AB  - The synthesis of polycyclic N-heteroaromatic compounds and their corresponding N
      oxides has been developed through electrochemical C-H functionalization of biaryl
      ketoximes. The oxime substrates undergo dehydrogenative cyclization when a Pt
      cathode is used, resulting in unprecedented access to a wide range of N
      heteroaromatic N-oxides. The products of the electrosynthesis are switched to the
      deoxygenated N-heteroaromatics by employing a Pb cathode through sequential anode
      promoted dehydrogenative cyclization and cathodic cleavage of the N-O bond in the
      initially formed N-oxide.

PMID- 30225910
TI  - Deletion of exons encoding carboxypeptidase domain of Nna1 results in Purkinje
      cell degeneration (pcd) phenotype.
AB  - Purkinje cell degeneration (pcd) was first identified in a spontaneous mouse
      mutant showing cerebellar ataxia. In addition to cerebellar Purkinje cells (PCs),
      retinal photoreceptors, mitral cells in the olfactory bulb, and a discrete
      subpopulation of thalamic neurons also degenerate in the mutant brains. The gene
      responsible for the pcd mutant is Nna1, also known as ATP/GTP binding protein 1
      or cytosolic carboxypeptidase-like 1, which encodes a zinc carboxypeptidase
      protein. To investigate pathogenesis of the pcd mutation in detail, we generated
      a conditional Nna1 allele targeting the carboxypeptidase domain at C-terminus.
      After Cre recombination and heterozygous crossing, we generated Nna1 knockout
      (KO) mice and found that the Nna1 KO mice began to show cerebellar ataxia at
      postnatal day 20 (P20). Most PCs degenerated until 4-week-old, except lobule X.
      Activated microglia and astrocytes were also observed in the Nna1 KO cerebellum.
      In the mutant brain, the Nna1 mRNA level was dramatically reduced, suggesting
      that nonsense-mediated mRNA decay occurs in it. Since the Nna1 protein acts as a
      de-glutamatase on the C-terminus of alpha-tubulin and beta-tubulin, increased
      polyglutamylated tubulin was detected in the Nna1 KO cerebellum. In addition, the
      endoplasmic reticulum stress marker, C/EBP homologous protein (CHOP), was up
      regulated in the mutant PCs. We report the generation of a functional Nna1
      conditional allele and possible mechanisms of PC death in the Nna1 KO in the
      cerebellum. OPEN PRACTICES: This article has received a badge for *Open
      Materials* because it provided all relevant information to reproduce the study in
      the manuscript. The complete Open Science Disclosure form for this article can be
      found at the end of the article. More information about the Open Practices badges
      can be found at https://cos.io/our-services/open-science-badges/.

PMID- 30225911
TI  - Risk of suicide attempts among colorectal cancer patients: A nationwide
      population-based matched cohort study.
AB  - OBJECTIVE: Patients with colorectal cancer (CRC) have been found to have a higher
      risk of suicide in limited-number studies. However, data on the actual incidence
      rate of suicide remain scarce. METHODS: Using Taiwan's National Health Insurance
      Research Database, we examined whether patients with CRC in Taiwan are at
      increased risk of suicide attempts. In this retrospective matched cohort study,
      data of 96 470 cases of CRC during 1 January 2000 to 31 December 2010 were
      collected. The control group was derived from general population by frequency
      matching 2 individuals without CRC for each individual with CRC by year of CRC
      diagnosis, age, and sex. The suicide risk in the CRC group compared with the
      control group was determined through Cox proportional hazard regression. We also
      compared the Kaplan-Meier analyses to competing risk cumulative incidence curves
      using the Aalen-Johansen estimator. RESULTS: A statistically significant 103%
      higher risk of suicide was observed in the CRC group compared with the control
      group (adjusted hazard ratio: 2.03; 95% confidence ratio: 1.60-2.56). Additional
      stratified analyses revealed a significantly elevated risk across almost all
      demographic groups but limited to rectum location, short follow-up time (<5
      years), and without comorbidity. CONCLUSIONS: Our study suggested that patients
      with CRC in Taiwan have an elevated risk of suicide. Oncologists should pay
      attention to these patients and should consider referring them for psychological
      consultation to prevent suicide.

PMID- 30225913
TI  - Neuropeptide Y and orexin immunoreactivity in the sparrow brain coincide with
      seasonal changes in energy balance and steroids.
AB  - The transition between the breeding and nonbreeding states is often marked by a
      shift in energy balance. Despite this well-known shift in energy balance, little
      work has explored seasonal differences in the orexigenic neuropeptides that
      regulate food intake in wild animals. Here we tested the hypothesis that free
      living male song sparrows (Melospiza melodia) show seasonal changes in energetic
      state, circulating steroids, and both neuropeptide Y (NPY) and orexin (OX)
      immunoreactivity. Nonbreeding song sparrows had more fat and muscle, as well as a
      ketone and triglyceride profile suggesting a greater reliance on lipid reserves.
      Breeding birds had higher plasma androgens; however, nonbreeding birds did
      maintain androgen precursors in circulation. Nonbreeding birds had more NPY
      immunoreactivity, specifically in three brain regions: lateral septum, bed
      nucleus of the stria terminalis, and ventral tegmental area. Furthermore,
      nonbreeding birds had more OX immunoreactivity in multiple brain regions. Taken
      together, the data indicate that a natural shift in energy balance is associated
      with changes in NPY and OX in a region-specific manner.

PMID- 30225912
TI  - Somatotopic organization of central arbors from nociceptive afferents develops
      independently of their intact peripheral target innervation.
AB  - Functionally important regions of sensory maps are overrepresented in the sensory
      pathways and cortex, but the underlying developmental mechanisms are not clear.
      In the spinal cord dorsal horn (DH), we recently showed that paw innervating
      Mrgprd+ nonpeptidergic nociceptors display distinctive central arbor morphologies
      that well correlate with increased synapse transmission efficiency and heightened
      sensitivity of distal limb skin. Given that peripheral and central arbor
      formation of Mrgprd+ neurons co-occurs around the time of birth, we tested
      whether peripheral cues from different skin areas and/or postnatal reorganization
      mechanisms could instruct this somatotopic difference among central arbors. We
      found that, while terminal outgrowth/refinement occurs during early postnatal
      development in both the skin and the DH, postnatal refinement of central
      terminals precedes that of peripheral terminals. Furthermore, we used single-cell
      ablation of Ret to genetically disrupt epidermal innervation of Mrgprd+ neurons
      and revealed that the somatotopic difference among their central arbors was
      unaffected by this manipulation. Finally, we saw that region-specific Mrgprd+
      central terminal arbors are present from the earliest postnatal stages, before
      skin terminals are evident. In summary, we find that region-specific organization
      of Mrgprd+ neuron central arbors is present shortly after initial central
      terminal formation, which likely develops independently of peripheral target
      innervation. Our data suggest that either cell-intrinsic and/or DH prepatterning
      mechanisms are likely to establish this somatotopic difference.

PMID- 30225914
TI  - Interfacial Sulfur Functionalization Anchoring SnO2 and CH3 NH3 PbI3 for Enhanced
      Stability and Trap Passivation in Perovskite Solar Cells.
AB  - Trap states at the interface or in bulk perovskite materials critically influence
      perovskite solar cells performance and long-term stability. Here, a strategy for
      efficiently passivating charge traps and mitigating interfacial recombination by
      SnO2 surface sulfur functionalization is reported, which utilizes xanthate
      decomposition on the SnO2 surface at low temperature. The results show that
      functionalized sulfur atoms can coordinate with under-coordinated Pb2+ ions near
      the interface. After device fabrication under more than 60 % humidity in ambient
      air, the efficiency of methylammonium lead iodide (MAPbI3 ) perovskite solar
      cells based on sulfur-functionalized SnO2 increased from 16.56 % to 18.41 % with
      suppressed hysteresis, which resulted from the accelerated interfacial charge
      transport kinetics and decreased traps in bulk perovskite by interfacial sulfur
      functionalization. Additionally, thermally stimulated current studies show the
      decreased trap density in the shallow trap area after interfacial sulfur
      functionalization. The interfacial sulfur functionalized solar cells without
      sealing also exhibited considerable retardation of solar cell degradation with
      only 10 % degradation after 70 days air storage. This work demonstrates a facile
      sulfur functionalization strategy by using xanthate decomposition on SnO2
      surfaces to obtain highly efficient perovskite solar cells.

PMID- 30225915
TI  - Patient-reported outcomes of breast reconstruction in older women: Audit of a
      large metropolitan public/private practice in Sydney, Australia.
AB  - OBJECTIVE: Older age is associated with lower rates of breast reconstruction (BR)
      for women requiring mastectomy. This study compared patient-reported outcomes
      between women aged 60 years and older who had received mastectomy and BR with
      those who received no BR (NBR). METHODS: About 135 women aged 60 or over treated
      between 2009 and 2016 with mastectomy only (N = 87) or mastectomy with BR (N =
      48) for primary breast cancer completed patient-reported outcome measures using a
      set of validated questionnaires. Reasons for choosing or declining BR were also
      explored using a set of nonvalidated questionnaires. RESULTS: Patients who
      received BR were generally younger (P = <0.001) and reported greater satisfaction
      with their bodies (P = 0.048) than NBR patients. Patients with autologous
      reconstruction reported greater satisfaction with their breasts than implant
      based reconstruction patients. Both BR and NBR patients reported good quality of
      life, low pain scores, good body image, and low levels of decisional regret.
      CONCLUSIONS: These data do not identify any quality of life-related reasons to
      not offer clinically fit, well-informed older women the option of BR.

PMID- 30225916
TI  - All-Cause and Cause-Specific Mortality Trends of End-Stage Renal Disease due to
      Lupus Nephritis from 1995 to 2014.
AB  - BACKGROUND/OBJECTIVE: The premature mortality among patients with end-stage renal
      disease due to lupus nephritis (LN-ESRD) persisted in the U.S. between 1995 and
      2006. We extended the analysis until 2014 for the latest trend and also examined
      key cause-specific mortality trends. METHODS: Using the national registry of ESRD
      patients, we identified all patients with incident LN-ESRD between January 1,
      1995 and December 31, 2014, divided into four five-year cohorts by calendar year
      of ESRD onset (1995-1999, 2000-2004, 2005-2009, 2010-2014). We assessed mortality
      rates within each cohort. We examined temporal trends in all-cause mortality and
      cause-specific mortality, adjusting for covariates. RESULTS: We identified 20,974
      individuals with incident LN-ESRD between 1995-2014. The mortality rate per 100
      patient-years declined from 11.1 (95% CI 10.4-11.8) in 1995-1999 to 6.7 (95% CI
      6.2-7.2) in 2010-2014 (p trend <0.01). Adjusted mortality hazard ratios in 2010
      2014, compared with 1995-1999 were 0.68 (95% CI 0.58-0.78) for white patients,
      0.67 (95% CI 0.57-0.78) for African Americans, and 0.51 (95% CI 0.38-0.69) for
      Hispanics. Deaths due to cardiovascular disease (CVD) and infection declined by
      44% and 63%, respectively, from 1995-1999 to 2010-2014 (both p trend <0.01).
      CONCLUSION: Between 1995 and 2014, there was a considerable reduction in all
      cause mortality among white, African American, and Hispanic patients in recent
      years, with reduced risk of death due to CVD and infections. Collectively, these
      trends provide an important benchmark of improving care in this high-risk
      population. This article is protected by copyright. All rights reserved.

PMID- 30225917
TI  - Predictors of responses to clinic-based childhood obesity care.
AB  - BACKGROUND/OBJECTIVE: Lifestyle modification is the therapy of choice for
      childhood obesity, yet the response rate is variable and may be affected by
      genetic factors. We aimed to investigate predictors of poor response to lifestyle
      modification obesity treatment in children. METHODS: A prospective cohort study
      of 434 youths (64.5% females) between 4 and 20 years of age undergoing a standard
      care of lifestyle modification obesity management for 35.9 +/- 20.8 months at
      Yale Childhood Obesity Clinic, USA. The primary outcome was a "poor response,"
      defined as the quintile with the largest increase in BMI Z-score over time. The
      secondary outcome was the endpoint BMI Z-score. Covariates investigated were sex,
      baseline pubertal status and degree of obesity, race, biochemical profile, and
      family history of overweight. A subsample (n = 214) had FTO genotyping (SNP
      rs8050136) tested. RESULTS: Males (hazard ratio [HR] = 5.35, 95% confidence
      interval [CI] [3.32-8.61], P < 0.0001) and pubertal adolescents (HR = 2.78, [1.40
      5.50], P = 0.003) compared to prepubertal children were more prone to respond
      poorly. Baseline degree of obesity was associated with relative protection from
      responding poorly (HR per BMI Z-score unit = 0.32, [0.17-0.61], P = 0.0006).
      Carriers of the FTO obesity-predisposing allele (AA genotype) were protected from
      responding poorly compared to non-carriers (CC genotype) (HR = 0.33, [0.12-0.88],
      P = 0.028). CONCLUSIONS: Boys and pubertal adolescents are more prone to respond
      poorly to standard obesity care while those with greater baseline degree of
      obesity and carriers of the FTO obesity-predisposing allele are not.

PMID- 30225918
TI  - Surprisingly low incidence of left ventricular thrombosis in anterior ST-segment
      elevation myocardial infarction.

PMID- 30225919
TI  - Modeling semicontinuous longitudinal data with order constraints.
AB  - Semicontinuous longitudinal data are characterized by within-subjects repeated
      measurements that either indicate absence of abnormality or reflect different
      amount of abnormality. Joint models for semicontinuous longitudinal data have
      been increasingly receiving attention in the literature. Such models permit
      flexible characterization of covariates-outcome associations. Order-restricted
      statistical inference has been well established in the literature but has not yet
      been applied to joint models for semicontinuous longitudinal data. We incorporate
      general order-restricted inference into the general joint models for
      semicontinuous longitudinal data previously proposed. We develop computational
      methods to address general order restrictions. Through simulations and a real
      data example, we demonstrate the advantages of order-restricted inference in
      terms of increased power in hypothesis testing and increased precision in
      parameter estimation.

PMID- 30225920
TI  - Application of kriging models for a drug combination experiment on lung cancer.
AB  - Combinatorial drugs have been widely applied in disease treatment, especially
      chemotherapy for cancer, due to its improved efficacy and reduced toxicity
      compared with individual drugs. The study of combinatorial drugs requires
      efficient experimental designs and proper follow-up statistical modeling
      techniques. Linear and nonlinear models are often used in the response surface
      modeling for such experiments. We propose the use of kriging models to better
      depict the response surfaces of combinatorial drugs. We illustrate our method via
      a drug combination experiment on lung cancer and further show how proper
      experimental designs can reduce the necessary run size. We demonstrate that only
      27 runs are needed to predict all 512 runs in the original experiment and achieve
      better precision than existing analyses.

PMID- 30225921
TI  - Enantioselective Lewis Acid Catalyzed ortho Photocycloaddition of Olefins to
      Phenanthrene-9-carboxaldehydes.
AB  - Visible-light irradiation (lambda=457 nm) enabled the enantioselective ortho
      photocycloaddition of olefins to phenanthrene-9-carboxaldehydes (15 examples, 46
      93 % yield, 82-98 % ee). A chiral oxazaborolidine Lewis acid (20 mol %) was
      employed as the catalyst. It operates by coordination to the aldehyde inducing a
      bathochromic absorption shift beyond the npi* absorption of the uncomplexed
      aldehyde. At long wavelengths the Lewis acid complex is exclusively excited;
      within the complex, one enantiotopic face of the aromatic aldehyde is efficiently
      shielded. Lewis acid coordination also alters the type selectivity and the simple
      diastereoselectivity of the photocycloaddition.

PMID- 30225922
TI  - Comparative quantitative clinical, neuroimaging, and functional profiles in
      children with acute flaccid myelitis at acute and convalescent stages of disease.
AB  - AIM: To quantify characteristics in acute flaccid myelitis (AFM) at acute and
      convalescent stages. METHOD: This was a retrospective case series of children
      with AFM evaluated at a single institution in the USA (2014-2017). Acute
      inflammatory/ischemic myelopathies were excluded. Neurological assessments and
      segmental quantitative analysis of signal abnormalities on magnetic resonance
      imaging (MRI) of the brain and spinal cord were performed. RESULTS: Sixteen
      patients (11 males, five females) were evaluated. Median age at onset was 4 years
      (interquartile range [IQR] 3-6y). All had parainfectious acute-onset limb
      weakness, lower motor neuron examination, and spinal fluid pleocytosis. On acute
      spinal cord MRI, longitudinally extensive T2 hyperintensities were identified
      throughout the spinal cord mostly within grey matter; five out of 12 patients had
      dorsal brainstem T2 hyperintensities. At a median of 2 months follow-up (IQR 2
      3mo), spinal cord MRI improved in seven out of nine patients although focal T2
      hyperintensities persisted in cervical and lumbar grey matter. At a median follow
      up of 4 months (IQR 2-6mo), Medical Research Council sum score rose from a median
      of 29 to 32; distal muscle groups improved more than proximal ones; four out of
      16 patients were ventilator-dependent; and two out of 16 patients were
      quadriplegic. INTERPRETATION: While patients may show marked improvement on
      neuroimaging from acute to convalescent stages, the majority of children with AFM
      have limited motor recovery and continued disability. Clinicians should consider
      the timing of clinical and neuroimaging exams when assessing diagnosis and
      prognosis. WHAT THIS PAPER ADDS: During the 2014 to 2017 acute flaccid myelitis
      outbreak in the USA, clinical recovery was better in distal than proximal muscle
      groups. Lumbar spinal cord showed more residual abnormalities at convalescence.

PMID- 30225923
TI  - Development of simulation combining a physical heart model and three-dimensional
      system for electrophysiology training.
AB  - BACKGROUND: A new three-dimensional heart anatomical simulator (3D HAS) has been
      created combining a physical heart model with an electroanatomic mapping (EAM)
      system. The aim of this study is to describe the development and the validation
      process of this device. METHODS: We developed the 3D HAS combining a physical
      heart model with an EAM system. This simulator was then validated by 10
      electrophysiologists, subdivided in two groups based on their experience in
      electrophysiology procedures. The performance of the experts was compared to the
      one of the novices in achieving three different tasks: fluoroless reconstruction
      of the right atrium, coronary sinus cannulation, and deployment of a linear
      ablation lesion in the cavotricuspid isthmus. For each operator, a score was
      calculated based on objective parameter for each task and for the overall
      performance. RESULTS: The 3D HAS was located in an environment that allowed use
      of the main features of the EAM system including contact force sensing. No
      technical issue was encountered during the validation process. The experts'
      performance was significantly better than the one of the novices both overall (P
      = 0.009) and in each task (right atrium reconstruction, P = 0.016; coronary sinus
      cannulation, P = 0.008; ablation lesion, P = 0.03). CONCLUSIONS: The 3D HAS is
      reliable and allows use of the main features of an EAM system in the right
      atrium. The ability to discriminate different levels of experience suggests that
      this simulator is enough realistic and could be useful for electrophysiology
      training.

PMID- 30225925
TI  - Double-Helical Nanostructures with Controllable Handedness in Bulk Diblock
      Copolymers.
AB  - Double-helical nanostructures with controllable handedness in bulk materials is
      of high interest in science and technology for the design and fabrication of new
      materials, in particular metamaterials, which mimic their natural homologues or
      even show superior properties. Herein, we report the fabrication of double
      helical structures with controlled handedness through the self-assembly of an
      achiral diblock copolymer doped with d- and l-tartaric acid (TA). The helices
      showed clear handedness dependence on the chirality of the TA. The chiral
      arrangement of different achiral tectonic units, such as nanoparticles and
      organic molecules, was confirmed using this helical structure as a template. The
      double-helical structure will provide new knowledge for understanding the
      function of helices, and will enable the application of these systems as
      chiroptical materials.

PMID- 30225924
TI  - Effects of socioeconomic status on clinical outcomes with ventricular assist
      devices.
AB  - BACKGROUND: Lower socioeconomic status (SES) is a known risk factor for worse
      outcomes after major cardiovascular interventions. Furthermore, individuals with
      lower SES face barriers to evaluation for advanced heart failure therapies,
      including ventricular assist device (VAD) implantation. HYPOTHESIS: Examination
      of the effects of individual determinants of SES on VAD outcomes will show
      similar survival benefit in patients with lower compared with higher SES.
      METHODS: All VAD implants at the University of Florida from January 2008 to
      December 2015 were reviewed. Patient-level determinants of SES included place of
      residence, education level, marital status, insurance status, and financial
      resources stratified by percent federal poverty level. Survival or
      transplantation at 1 year, 30-day readmission, implant length of stay (LOS), and
      an aggregate of VAD-related complications were assessed in univariate fashion and
      multivariable regression modeling. RESULTS: A total of 111 patients were included
      (mean age at the time of implant 57.6 years, 82.8% men). More than half received
      destination therapy. At 1 year, 78.3% were alive on device support or had
      undergone successful transplantation. There were no differences in survival, 30
      day readmission, or aggregate VAD complications by the SES category. Although
      patients with lower levels of education had longer LOS in univariate analysis, on
      multivariable ordinal regression modeling, this relationship was no longer seen.
      CONCLUSIONS: Patients with lower SES receive the same survival benefit from VAD
      implantation and are not more likely to have 30-day readmissions, complications
      of device support, or prolonged implant LOS. Therefore, VAD implantation should
      not be withheld based on these parameters alone.

PMID- 30225926
TI  - Procedural management of rhinophyma: A comprehensive review.
AB  - BACKGROUND: Rhinophyma is a cosmetically deforming disease characterized by
      nodular overgrowth of the lower 2/3 of the nose and is considered the end stage
      of acne rosacea. AIMS: Review the spectrum of procedural techniques for treatment
      of rhinophyma with a focus on the advantages and disadvantages of each modality.
      METHODS: A comprehensive literature search was conducted using the search terms
      "rhinophyma," "treatment," and "surgery" in PubMed. Case reports, case series,
      and small retrospective trials using procedural techniques for management of
      rhinophyma were included for review. Animal studies, non-English articles, and
      reports of medical treatment of rhinophyma were excluded. RESULTS: There are
      currently no prospective, randomized controlled studies evaluating procedural
      management of rhinophyma. The most commonly employed treatments include scalpel
      excision, resection with heated knives, dermabrasion, electrosurgery and lasers,
      specifically carbon dioxide (CO2 ) and erbium:yttrium-aluminum-garnet (Er:YAG).
      The main complication associated with complete excision of rhinophymatous tissue
      is excessive scarring. To correct for this adverse effect, partial or tangential
      excision with preservation of underlying adnexal structures is now the accepted
      technique, irrespective of the chosen modality. CONCLUSION: There is no accepted
      gold standard for management of rhinophyma, and each modality succeeds in
      maintaining hemostasis, reducing scarring and achieving satisfactory cosmesis to
      different degrees. There is a conflicting data on the theoretical risk of
      recurrence with partial excision due to incomplete removal of tissue. Further
      studies evaluating this risk and alternate methods of prevention are required.

PMID- 30225928
TI  - Comparative Effectiveness of Combination Therapy with Statins and Angiotensin
      Converting Enzyme Inhibitors versus Angiotensin II Receptor Blockers in Patients
      with Coronary Heart Disease: A Nationwide Population-Based Cohort Study in Korea.
AB  - STUDY OBJECTIVE: Patients with coronary heart disease (CHD) frequently use the
      combination of a statin and renin-angiotensin-aldosterone system (RAAS) blocker,
      an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor
      blocker (ARB), to control lipid levels and blood pressure, respectively, and the
      use of ARBs is increasing in Korean patients. Few studies are available, however,
      that have compared combination therapy with statin-ACEIs versus statin-ARBs. The
      objective of this study was to evaluate whether ARBs are associated with a
      reduced risk of major adverse cardiovascular and cerebrovascular events (MACCEs)
      compared with ACEIs when used in combination with statins in patients with
      established CHD. DESIGN: Population-based retrospective cohort study. DATA
      SOURCE: Korean National Health Insurance Service-National Sample Cohort database.
      PATIENTS: A total of 6577 adults who started statin-RAAS blocker combination
      therapy (1870 in the statin-ACEI cohort and 4707 in the statin-ARB cohort) after
      being diagnosed with CHD between January 2003 and December 2013 were included. Of
      these, 3676 propensity score-matched patients (1838 in the statin-ACEI cohort and
      1838 in the statin-ARB cohort) were included in the final analyses. MEASUREMENTS
      AND MAIN RESULTS: The primary outcome was MACCE (major adverse cardiovascular and
      cerebrovascular events), a composite of cardiovascular mortality, nonfatal
      myocardial infarction (MI), ischemic stroke, and revascularization. Incidences
      and incidence rates of MACCE were calculated to estimate the differences between
      the two cohorts. Hazard ratios (HRs) and 95% confidence intervals (CIs) were
      estimated by using a Cox proportional hazard model. The incidence of MACCE was
      19.9% and 14.7%, and incidence rates were 11.7 and 8.1 per 100 person-years in
      the statin-ACEI and statin-ARB cohorts, respectively. The risk of MACCE was
      significantly lower in the statin-ARB cohort (adjusted HR 0.69, 95% CI 0.59
      0.81). CONCLUSION: A MACCE was less likely to occur in patients who received a
      statin-ARB than in those who received a statin-ACEI. Similar trends were seen in
      cardiovascular mortality and the occurrence of recurrent MI but not stroke. The
      availability of statin-ARB fixed-dose combinations may have contributed to the
      improved outcomes in the statin-ARB cohort by reducing pill burden and improving
      medication adherence. Further research is warranted to validate our findings and
      to address whether a particular statin-ARB combination is more effective than
      other combinations.

PMID- 30225927
TI  - Sexually transmitted infections and HIV RNA levels in blood and anogenital
      compartments among Thai men who have sex with men before and after antiretroviral
      therapy: implication for Treatment as Prevention programme.
AB  - INTRODUCTION: Sexually transmitted infections (STIs) are common among HIV
      positive men who have sex with men (MSM). There have been concerns that
      undiagnosed and untreated STIs could undermine efforts to use antiretroviral
      therapy (ART) for prevention due to genital secretion infectiousness. We
      evaluated the correlation between STIs and HIV RNA in anogenital compartments
      among HIV-positive MSM before and after ART. METHODS: MSM participants newly
      diagnosed with HIV were offered ART regardless of CD4 count during November 2012
      to November 2015. Syphilis serology, oropharyngeal swab, rectal swab, urine
      collection for gonorrhoea and chlamydia nucleic acid amplification testing, and
      HIV RNA measurement in blood, semen and rectal samples were performed at
      baseline, 12 and 24 months thereafter. RESULTS: Of 143 HIV-positive MSM, 16.1%
      had syphilis, 23.1% had gonorrhoea and 32.8% had chlamydia at baseline.
      Participants with STIs at baseline had higher median HIV RNA levels in blood
      plasma (p = 0.053), seminal plasma (p = 0.01) and rectal secretions (p = 0.002)
      than those without STIs. Multivariate models identified HIV RNA 100,000 to
      500,000 (OR 6.74, 95% CI 2.24 to 20.28, p = 0.001) and >500,000 (OR 9.39, 95% CI
      1.08 to 81.72, p = 0.04) copies/mL in blood, CD4 count <350 cells/mm3 (OR 4.20,
      95% CI 1.05 to 16.70, p = 0.04) and having any STIs (OR 2.62, 95% CI 1.01 to 6.80
      p = 0.047) to be associated with detectable (>40 copies/mL) seminal plasma HIV
      RNA. Having chlamydia at any sites (OR 3.17, 95% CI 1.07 to 9.44, p = 0.04) was
      associated with detectable rectal HIV RNA. Incidences of syphilis, gonorrhoea and
      chlamydia were 13.4, 16.4 and 18.1 per 100 person-years respectively. Nine
      participants had detectable HIV RNA (five in blood, one in semen, two in rectal
      samples and one in both blood and rectal samples) at 12 and/or 24 months after
      ART. CONCLUSIONS: STIs were extremely common among HIV-positive MSM prior to and
      after ART. ART effectively reduced HIV RNA in all compartments. The correlation
      between STIs and anogenital HIV RNA, especially prior to ART and likely until
      complete HIV RNA suppression from ART is achieved, points to the importance of
      integrating asymptomatic STIs screening into Treatment as Prevention programme
      for MSM.

PMID- 30225930
TI  - The digital human forearm and hand.
AB  - How changes in anatomy affect joint biomechanics can be studied using
      musculoskeletal modelling, making it a valuable tool to explore joint function in
      healthy and pathological joints. However, gathering the anatomical, geometrical
      and physiological data necessary to create a model can be challenging. Very few
      integrated datasets exist and even less raw data is openly available to create
      new models. Therefore, the goal of the present study is to create an integrated
      digital forearm and make the raw data available via an open-access database. An
      un-embalmed cadaveric arm was digitized using 7T MRI and CT scans. 3D geometrical
      models of bones, cartilage, muscle and muscle pathways were created. After MRI
      and CT scanning, physiological muscle parameters (e.g. muscle volume, mass,
      length, pennation angle, physiological cross-sectional area, tendon length) were
      obtained via detailed dissection. After dissection, muscle biopsies were fixated
      and confocal microscopy was used to visualize and measure sarcomere lengths. This
      study provides an integrated anatomical dataset on which complete and accurate
      musculoskeletal models of the hand can be based. By creating a 3D digital human
      forearm, including all relevant anatomical parameters, a more realistic
      musculoskeletal model can be created. Furthermore, open access to the anatomical
      dataset makes it possible for other researchers to use these data in the
      development of a musculoskeletal model of the hand.

PMID- 30225929
TI  - Effects of radiofrequency on adipose tissue: A systematic review with meta
      analysis.
AB  - BACKGROUND: Equipment that acts in the reduction in adipose tissue are becoming
      widely investigated. One of the resources that begin to gain recognition is
      radiofrequency. PURPOSE: To verify the existence of scientific evidence and the
      methodological quality of the articles on the effects of radiofrequency in the
      reduction in adipose tissue. METHODOLOGY: Systematic review with meta-analysis on
      the effects of radiofrequency on adipose tissue. The research was carried out
      using several databases and including experimental studies only in humans. The
      evaluation of the methodological quality of the articles was done based on the
      PEDro Scale. RESULTS: Twelve articles related with adipose tissue and cellulitis
      were included. There was a great variability of protocols, and the methodological
      quality was generally low and the methods most used for the evaluation of results
      were anthropometry, photography, and histopathology. Clinical results suggest a
      positive effect of radiofrequency on the reduction in adipose tissue, proving an
      increase in adipocyte lipolysis. After statistical analysis, it was verified that
      the anthropometry presented questionable results. CONCLUSION: The clinical
      results of the studies point to the positive effects of radiofrequency on the
      reduction in adipose tissue; however, the low methodological make this topic
      still debatable, requiring more controlled studies.

PMID- 30225931
TI  - Comparison of a novel predictor of venous thromboembolic complications in
      inflammatory bowel disease with current predictors.
AB  - BACKGROUND AND AIM: Venous thromboembolism (VTE) is a common complication of
      inflammatory bowel disease (IBD). The aim of the present study was to identify
      predictors of VTE in hospitalized patients with IBD. METHODS: Patients with IBD
      who were hospitalized from February 2015 to March 2016 at the Chiba University
      Hospital were included. VTE was detected using enhanced computed tomography, and
      VTE onset within 2 months after admission was assessed. Predictors of VTE onset
      were investigated with clinical factors during hospitalization. Availability of
      the Caprini risk assessment model and Padua prediction score at the time of
      admission was also assessed. RESULTS: Seventy-two patients with IBD were
      hospitalized, and central venous catheters were placed in 43 of the 72 patients.
      During the observation period, VTE occurred in six patients (8.3%); however, none
      died as a result of the condition. Cox proportional hazards regression analysis
      identified D-dimer values on admission as a risk factor that was highly
      associated with VTE onset (hazard ratio = 1.590; 95% confidence interval, 1.132
      2.233; P = 0.007) and significantly predicted the occurrence of VTE using the
      receiver operating characteristic curve (P = 0.005, area under the curve =
      0.893). However, Caprini risk assessment model and Padua prediction scores were
      not useful tools for predicting VTE onset in patients with IBD. CONCLUSION: In
      hospitalized patients with IBD, D-dimer values were highly associated with VTE
      onset. Therefore, measurement of D-dimer values on admission is critical for the
      management of thromboembolic complications in patients with IBD.

PMID- 30225932
TI  - Root and canal morphology of maxillary premolar teeth in an Egyptian
      subpopulation using two classification systems: a cone beam computed tomography
      study.
AB  - AIM: To investigate the number of roots and root canal configurations using two
      coding systems and the root canal diverging and merging levels in extracted
      maxillary premolars in an Egyptian subpopulation using cone beam computed
      tomography (CBCT). METHODOLOGY: A total of 700 maxillary premolars were examined
      using CBCT in an Egyptian subpopulation. The number of roots was identified, and
      root canal configurations were classified according to Vertucci's classification
      and a new system for classifying root and canal morphology. In addition, the
      position where roots bifurcated and the levels where canals merged or diverged
      were identified. Fisher's exact test and independent t-test were used for
      statistical analysis, and the level of significance was set at 0.05 (P = 0.05).
      RESULTS: More than half of maxillary first premolars were double-rooted, and the
      majority of maxillary second premolars were single-rooted (P < 0.001). Most of
      the double-rooted samples had bifurcations in the middle of the root. According
      to the Vertucci classification, canal configuration type IV was the most common
      in both first and second maxillary premolars. According to the new system, the
      code 2 FP B1 P1 was the most common for maxillary first premolars, whilst 2 SP B1
      P1 , 1 SP2 and 1 SP2-1 codes were the most common for maxillary second premolars.
      The three-canalled morphology in double- and three-rooted maxillary premolars had
      considerable variations. Root canal merging and diverging levels were comparable
      in both tooth types. CONCLUSION: Maxillary premolars in this Egyptian
      subpopulation had a wide range of root and canal anatomical variations.
      Clinicians should be aware of where canals merge and diverge to facilitate the
      treatment of all canals. The new system for classifying canal morphology
      describes the root and canal configurations in a more accurate and practical
      manner compared to the Vertucci classification.

PMID- 30225933
TI  - Severity in polycystic liver disease is associated with aetiology and female
      gender: Results of the International PLD Registry.
AB  - BACKGROUND & AIMS: Polycystic liver disease (PLD) occurs in two genetic
      disorders, autosomal-dominant polycystic kidney disease (ADPKD) and autosomal
      dominant polycystic liver disease (ADPLD). The aim of this study is to compare
      disease severity between ADPKD and ADPLD by determining the association between
      diagnosis and height-adjusted total liver volume (hTLV). METHODS: We performed a
      cross-sectional analysis with hTLV as endpoint. Patients were identified from the
      International PLD Registry (>10 liver cysts) and included in our analysis when
      PLD diagnosis was made prior to September 2017, hTLV was available before volume
      reducing therapy (measured on computed tomography or magnetic resonance imaging)
      and when patients were tertiary referred. Data from the registry were retrieved
      for age, diagnosis (ADPKD or ADPLD), gender, height and hTLV. RESULTS: A total of
      360 patients (ADPKD n = 241; ADPLD n = 119) met our inclusion criteria. Female
      ADPKD patients had larger hTLV compared with ADPLD (P = 0.008). In a multivariate
      regression analysis, ADPKD and lower age at index CT were independently
      associated with larger hTLV in females, whereas in males a higher age was
      associated with larger hTLV. Young females (<=51 years) had larger liver volumes
      compared with older females (>51 years) in ADPKD. CONCLUSION: Aetiology is
      presented as a new risk factor associated with PLD severity. Young females with
      ADPKD represent a subgroup of PLD patients with the most severe phenotype
      expressed in hTLV.

PMID- 30225934
TI  - Improving the efficiency of individually randomized clinical trials by staggering
      the introduction of the intervention.
AB  - In cluster randomized trials, the introduction of the intervention can be
      staggered in different clusters, leading to a stepped wedge design. This strategy
      can lead to gains in efficiency, which might also translate to the context of
      individually randomized trials, though this has been relatively unexplored. Here,
      we present one illustrative example. We consider trials in which participants
      start in a control condition such as routine care and can cross over at any stage
      to the active intervention. We make the assumption that the effect of the
      intervention is the same however long the delay before a participant crosses over
      to the intervention condition. We consider designs for a trial with three
      repeated assessments, including a baseline, and show that a three-sequence design
      with staggered introduction of the intervention in two of the sequences estimates
      the treatment effect after one period more efficiently than a parallel groups
      design.

PMID- 30225935
TI  - Using metabarcoding to compare the suitability of two blood-feeding leech species
      for sampling mammalian diversity in North Borneo.
AB  - The application of high-throughput sequencing (HTS) for metabarcoding of mixed
      samples offers new opportunities in conservation biology. Recently, the
      successful detection of prey DNA from the guts of leeches has raised the
      possibility that these, and other blood-feeding invertebrates, might serve as
      useful samplers of mammals. Yet little is known about whether sympatric leech
      species differ in their feeding preferences, and whether this has a bearing on
      their relative suitability for monitoring local mammalian diversity. To address
      these questions, we collected spatially matched samples of two congeneric leech
      species Haemadipsa picta and Haemadipsa sumatrana from lowland rainforest in
      Borneo. For each species, we pooled ~500 leeches into batches of 10 individuals,
      performed PCR to target a section of the mammalian 16S rRNA locus and undertook
      sequencing of amplicon libraries using an Illumina MiSeq. In total, we identified
      sequences from 14 mammalian genera, spanning nine families and five orders. We
      found greater numbers of detections, and higher diversity of OTUs, in H. picta
      compared with H. sumatrana, with rodents only present in the former leech
      species. However, comparison of samples from across the landscape revealed no
      significant difference in mammal community composition between the leech species.
      We therefore suggest that H. picta is the more suitable iDNA sampler in this
      degraded Bornean forest. We conclude that the choice of invertebrate sampler can
      influence the detectability of different mammal groups and that this should be
      accounted for when designing iDNA studies.

PMID- 30225936
TI  - Reactivity of Selenocystine and Tellurocystine: Structure and Antioxidant
      Activity of the Derivatives.
AB  - l-Selenocystine (5) and l-tellurocystine (6) have been prepared and the
      reactivity of these amino acids, i.e., oxidation of 5 and 6, has been performed
      at various pH values. Hydrogen peroxide was used as an oxidant and it was treated
      with 5 and 6 in excess in acidic and basic media. Compound 5, upon oxidation,
      afforded SeIV and SeVI products. Selenocysteic acid [HO3 SeCH2 CH(NH2 )COOH] 9, a
      novel SeVI compound, was isolated and characterised by single-crystal X-ray
      diffraction studies. In contrast, l-tellurocystine, upon oxidation with H2 O2 ,
      afforded TeII and TeIV products. Zwitterionic organotellurolate(IV), [TeCl3 CH2
      CH(NH3 )COOH] 13, was isolated and characterised by NMR and IR spectroscopy, mass
      spectrometry and elemental analysis. Compound 13 crystallizes in an orthorhombic
      space group. l-Tellurocystine, when reduced with NaBH4 , produced the desired
      tellurolate intermediate, which was trapped with bromoacetic acid. Furthermore, l
      and d-tellurocysteine derivatives, [(RTeCH2 CH(NH2 )COOH) R=phenyl, substituted
      phenyl and naphthyl (24-39)] were synthesised and evaluated for their glutathione
      peroxidase (GPx)-like activities. The results show that l-tellurocysteine
      derivatives have higher activity than their D-tellurocysteine analogues. DFT
      calculations for l-tellurocysteine derivatives provided information about the
      bond lengths and bond angles. This study reveals that the introduction of
      naphthyl substituents (35-38) leads to twisted conformation of the amino acid
      derivatives.

PMID- 30225937
TI  - Effects of six types of aspirin combination medications for treatment of acute
      cerebral infarction in China: A network meta-analysis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Previous studies have shown that various aspirin
      combinations might be beneficial for the treatment of acute cerebral infarction
      (ACI). The aim of this study was to evaluate the efficacy of six aspirin
      combinations in the treatment of ACI using network meta-analysis (NMA). The
      performance of these combinations is then ranked according to results of this
      analysis. METHODS: Multiple databases were consulted to find randomized
      controlled trials (RCT) of six different aspirin combinations for the treatment
      of ACI. NMA was conducted on the data using stata (13.0) software. The odds ratio
      (OR) was calculated. The studies included in this paper were divided into a
      control group (aspirin alone) and an observation group (one of six aspirin
      combinations). RESULTS: A total of 103 eligible RCTs were identified. A total of
      13 317 cases were included in the study, and the results showed that the six
      types of aspirin combinations (aspirin with atorvastatin, ozagrel sodium, low
      molecular weight heparin [LMWH], clopidogrel, cilostazol and ginkgo damo) were
      all significantly superior (P < 0.05) to aspirin alone. The combination of
      aspirin with LMWH had the highest probability of being the most clinically
      efficacious intervention, with a surface under the cumulative ranking (SUCRA)
      curve of 79.1. The combination of aspirin with ozagrel sodium was the worst, with
      a SUCRA value of 29.7. WHAT IS NEW AND CONCLUSION: A combination of aspirin with
      LMWH is the best option among the six aspirin combinations considered for the
      treatment of ACI. The combination of aspirin with ozagrel sodium was ranked the
      last.

PMID- 30225939
TI  - BIOSEPARATIONS - 2018.

PMID- 30225938
TI  - Changes in mitral annular velocities after cardioversion of atrial fibrillation.
AB  - AIMS: The early diastolic mitral annular velocity (e') and mitral E/e' criteria
      for clinically evaluating diastolic dysfunction in patients with atrial
      fibrillation (AF) are almost the same as in patients with sinus rhythm. In this
      study, we aimed to investigate whether e' is useful to assess diastolic function
      in AF patients. METHODS: Thirty patients who underwent successful electric
      cardioversion (EC) due to persistent AF and who maintained sinus rhythm for 1
      month after EC were enrolled in this study. Transthoracic echocardiography was
      performed on all patients before and 1 month after EC. Standard diastolic
      parameters, the global longitudinal strain (GLS), and left ventricular (LV) twist
      were measured. RESULTS: Conventional Doppler parameters measured before EC were
      not significantly different from 1 month after EC. However, the lateral and
      septal e' were significantly decreased 1 month after EC (from 12.8 +/- 2.5 to 9.8
      +/- 2.3 cm/s and from 9.5 +/- 1.9 to 7.1 +/- 1.5 cm/s, respectively, P < 0.001).
      Likewise, the lateral and septal E/e' were also significantly increased 1 month
      after EC (P < 0.001). The GLS was significantly improved from -15.9 +/- 2.2% to 
      19.4 +/- 2.4% after EC (P < 0.001), as was the LV twist (from 5.8 +/- 1.7 degrees
      to 9.1 +/- 2.4 degrees , P < 0.001). CONCLUSION: We demonstrated that e' was
      significantly higher in AF compared with during sinus rhythm in the same
      patients. Thus, in AF patients, diastolic dysfunction should be suspected even
      when e' values are normal.

PMID- 30225941
TI  - Role of corneal nerves in ocular surface homeostasis and disease.
AB  - Corneal nerves are key components of the physiological system that controls
      ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic
      branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from
      the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory
      for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing
      temperature, chemical and mechanical stimuli, and pain, whereas, branches of the
      facial nerve (cranial nerve VII) contain motor nerves that control blinking and
      autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate
      tear production and secretion via feedback loops between the ocular surface,
      lacrimal glands and brain. Disruption of these nerves with interruption of neural
      feedback loops between the ocular surface and lacrimal glands can lead to corneal
      diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK).
      Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain
      controlling nervous centres may lead to neuropathic pain. Recently, medications
      that specifically target regeneration of corneal nerves have started to become
      available - and considering the high prevalence of diseases associated with
      corneal nerve dysfunction, these agents promise to fulfil a hitherto important
      unmet need. In this review, we explore the physiology of corneal nerves, the
      pathology of corneal nerve diseases and how these relate to neuropathic pain, NK
      and DED. We also discuss what novel treatments may be useful against diseases
      involving corneal nerves.

PMID- 30225942
TI  - Ring chromosome 6 in a child with anterior segment dysgenesis and review of its
      overlap with other FOXC1 deletion phenotypes.
AB  - Here, we report a patient with ring chromosome 6 [r(6)], associated with anterior
      segment dysgenesis (ASD) and other anomalies. The phenotype was due to a 1880 kb
      microdeletion at 6p25.3 identified by whole-genome array analysis, and was mainly
      attributable to a FOXC1 haploinsufficiency. Currently 37 patients with r(6) have
      been reported. We found that facial dysmorphism, ASD, heart anomalies, brain
      anomalies, and hearing loss are constant features only in severe cases of r(6),
      mainly related to hemizygosity of FOXC1. Thus, overlaps with other FOXC1 related
      phenotypes, such as the 6p25 deletion syndrome, Axenfeld-Rieger syndrome type 3,
      and ASD type 3. Contrarily, those patients whose r(6) does not disrupt FOXC1,
      have mild or moderate phenotypes and do not exhibit ASD.

PMID- 30225943
TI  - A modified DNA barcode approach to define trophic interactions between native and
      exotic pentatomids and their parasitoids.
AB  - The establishment of invasive Halyomorpha halys (Stal) outside of its native
      range may impact native species assemblages, including other pentatomids and
      their scelionid parasitoids. This has generated interest in defining species
      diversity and host-parasitoid associations in this system to better understand
      the impact of invasive alien species on trophic interactions in invaded regions.
      Information on scelionid-pentatomid associations in natural habitats is lacking,
      and species-level identification of these associations can be tenuous using
      rearing and dissection techniques. Naturally occurring pentatomid eggs were
      collected in areas where H. halys has established in Canada and were analysed
      using a modified DNA barcoding approach to define species-level trophic
      interactions. Identification was possible for >90% of egg masses. Eleven
      pentatomid and five scelionid species were identified, and trophic links were
      established. Approximately 70% of egg masses were parasitized; parasitism and
      parasitoid species composition were described for each species. Telenomus podisi
      Ashmead was the dominant parasitoid and was detected in all host species.
      Trissolcus euschisti Ashmead was detected in several host species, but was
      significantly more prevalent in Chinavia hilaris (Say) and Brochymena
      quadripustulata (Fabricius). Trissolcus brochymenae Ashmead and Tr. thyantae
      Ashmead were recorded sporadically. Parasitism of H. halys was 55%, and this
      species was significantly less likely to be parasitized than native pentatomids.
      The scelionid species composition of H. halys consisted of Te. podisi, Tr.
      euschisti and Tr. thyantae. Although these species cannot develop in fresh H.
      halys eggs, we demonstrate that parasitoids attempt to exploit this host under
      field conditions.

PMID- 30225944
TI  - Feasibility of using a leadless patch monitor in community cohort studies: The
      Multi-ethnic Study of Atherosclerosis.

PMID- 30225945
TI  - How bacterioplankton community can go with cascade damming in the highly
      regulated Lancang-Mekong River Basin.
AB  - Rivers make vital contributions to the transport of water, sediment and nutrients
      from terrestrial to marine ecosystems. However, many large rivers worldwide are
      suffering from dam regulation. Increasing attention has been paid to
      bacterioplankton communities since they are highly responsive to river
      alterations and may influence biogeochemical processes. Here, a comprehensive
      study was conducted in the highly regulated Lancang-Mekong River Basin to address
      the question of how bacterioplankton communities respond to cascade damming. The
      results showed that dam constructions increased nutrient concentrations and
      threatened water quality in cascade reservoirs. Bacterioplankton cell abundance
      was reduced by damming, and alpha-diversity was inhibited in cascade reservoirs.
      Fortunately, however, river ecosystems were resilient after the remarkable
      disturbance caused by damming. Moreover, bacterioplankton community composition
      was significantly altered by cascade dams, including a shift in the dominant
      phylum from r-strategists to k-strategists. Meanwhile, according to GeoChip
      analysis, the functional composition of bacterioplankton was less affected than
      taxonomic composition. In addition, geographic and environmental features both
      followed a distance-decay relationship with community and functional composition,
      but the local environment condition was the dominant driver in the Lancang River.
      Therefore, the impoundments of cascade dams had significant impacts on
      bacterioplankton communities and more attention should be paid to the potential
      ecological consequences of river regulation.

PMID- 30225946
TI  - Retention on ART and predictors of disengagement from care in several alternative
      community-centred ART refill models in rural Swaziland.
AB  - INTRODUCTION: A broad range of community-centred care models for patients stable
      on anti-retroviral therapy (ART) have been proposed by the World Health
      Organization to better respond to patient needs and alleviate pressure on health
      systems caused by rapidly growing patient numbers. Where available, often a
      single alternative care model is offered in addition to routine clinical care. We
      operationalized several community-centred ART delivery care models in one public
      sector setting. Here, we compare retention in care and on ART and identify
      predictors of disengagement with care. METHODS: Patients on ART were enrolled
      into three community-centred ART delivery care models in the rural Shiselweni
      region (Swaziland), from 02/2015 to 09/2016: Community ART Groups (CAGs),
      comprehensive outreach care and treatment clubs. We used Kaplan-Meier estimates
      to describe crude retention in care model and retention on ART (including
      patients who returned to clinical care). Multivariate Cox proportional hazard
      models were used to determine factors associated with all-cause attrition from
      care model and disengagement with ART. RESULTS: A total of 918 patients were
      enrolled. CAGs had the most participants with 531 (57.8%). Median age was 44.7
      years (IQR 36.3 to 54.4), 71.8% of patients were female, and 62.6% fulfilled
      eligibility criteria for community ART. The 12-month retention in ART was 93.7%
      overall; it was similar between model types (p = 0.52). A considerable proportion
      of patients returned from community ART to clinical care, resulting in lower 12
      months retention in care model (82.2% overall); retention in care model was
      lowest in CAGs at 70.4%, compared with 86.3% in outreach and 90.4% in treatment
      clubs (p < 0.001). In multivariate Cox regression models, patients in CAGs had a
      higher risk of disengaging from care model (aHR 3.15, 95% CI 2.01 to 4.95, p <
      0.001) compared with treatment clubs. We found, however, no difference in
      attrition in ART between alternative model types. CONCLUSIONS: Concurrent
      implementation of three alternative community-centred ART models in the same
      region was feasible. Although a considerable proportion of patients returned back
      to clinical care, overall ART retention was high and should encourage programme
      managers to offer community-centred care models adapted to their specific
      setting.

PMID- 30225947
TI  - Public health nurses' experiences of using interpreters when meeting with Arabic
      speaking first-time mothers.
AB  - OBJECTIVES: The aim of this study was to investigate public health nurses'
      experiences of using interpreters when meeting with Arabic-speaking first-time
      mothers. DESIGN AND SAMPLE: An inductive qualitative design was used. Individual
      interviews were conducted with Swedish public health nurses (n = 11) with
      experience of working in child health care with interpreters when meeting with
      Arabic-speaking first-time mothers. MEASURES: Data were analyzed using
      qualitative content analysis. RESULTS: The analysis of the interviews resulted in
      one overarching theme: Having to accept and learn to incorporate interpreters
      when meeting with Arabic-speaking first-time mothers. Three subthemes were
      identified: (a) enabling an understanding of the situation of the mothers; (b)
      contributing to a trustful relationship; and (c) creating disturbing elements in
      the dialogue. CONCLUSIONS: Using interpreters optimized the conversation between
      the public health nurse and the Arab-speaking first-time mother; however, the
      complexity of using interpreters was also apparent.

PMID- 30225948
TI  - beta2-adrenoreceptor medications and risk of Parkinson disease.
AB  - OBJECTIVE: A recent study observed a 2-fold greater risk of Parkinson disease
      (PD) in relation to the beta2-adrenoreceptor antagonist propranolol and a
      markedly lower risk of PD for the beta2-adrenoreceptor agonist salbutamol. We
      examined whether confounding by clinical indication for these medications, that
      is, tremor and smoking-related pulmonary conditions, explained these
      associations. METHODS: In a large, population-based case-control study of United
      States Medicare beneficiaries in 2009 with diagnosis codes, procedure codes, and
      prescription data (48,295 incident PD cases, 52,324 controls), we examined the
      risk of PD in relation to use of selected beta antagonists (propranolol,
      carvedilol, metoprolol), the beta2 agonist salbutamol, and other medications used
      for the same clinical indications (primidone, inhaled corticosteroids). We
      adjusted for demographics, smoking, and overall use of medical care. We then
      examined the effect of also adjusting for clinical indication and applying
      medication exposure lagging. RESULTS: Propranolol appeared to increase PD risk
      (odds ratio [OR] = 3.62, 95% confidence interval [CI] = 3.31-3.96). When we
      adjusted for tremor or abnormal involuntary movement prior to the PD
      diagnosis/reference date and lagged propranolol exposure, the association was
      0.97 (95% CI = 0.80-1.18). Primidone, also used for tremor, was similarly
      sensitive to this adjustment and lagging. beta Antagonists not indicated for
      tremor appeared to reduce PD risk (carvedilol: OR = 0.77, 95% CI = 0.73-0.81;
      metoprolol: OR = 0.94, 95% CI = 0.91-0.97) and were insensitive to adjustment for
      indications and lagging. Neither salbutamol nor inhaled corticosteroids were
      consistently associated with PD risk. INTERPRETATION: beta2-adrenoreceptor
      agonists and antagonists do not appear to alter PD risk. Ann Neurol 2018;84:691
      701.

PMID- 30225950
TI  - Muscling up to improve heart failure prognosis.

PMID- 30225949
TI  - Serum S100A8/A9 and S100A12 Levels in Children with Polyarticular Forms of
      Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinical Inactive
      Disease During and Flare after Discontinuation of Anti-TNF Therapy.
AB  - OBJECTIVE: To determine the relationship between serum S100A8/A9 and S100A12 and
      the maintenance of clinical inactive disease (CID) in patients with polyarticular
      forms of juvenile idiopathic arthritis (PF-JIA) while on anti-tumor necrosis
      factor therapy (anti-TNF) and disease flare following withdrawal of anti-TNF.
      METHODS: In this prospective, multicenter study, 137 patients with PF-JIA were
      enrolled while in CID on anti-TNF. Patients were observed for the initial 6
      months. Those who maintained CID had anti-TNF withdrawn and were followed for 8
      months to assess for flare. Serum S100 levels were measured at baseline and when
      anti-TNF was withdrawn. Rank correlation, Mann-Whitney test, Kruskal-Wallis test,
      receiver-operating-characteristic (ROC) curve and Kaplan-Meier survival analysis
      were used to assess the relationship between S100 levels and maintenance of CID
      and disease flare. RESULTS: Twenty-four out of 130 (18%) evaluable patients lost
      CID while on anti-TNF, and 39 of 106 (37%) evaluable patients flared following
      anti-TNF withdrawal. S100A8/A9 and S100A12 levels were elevated in up to 45% of
      patients. In the ROC analysis, S100 levels did not predict maintenance of CID and
      disease flare. Elevated S100A8/A9 levels did not predict disease flare within 30,
      60, 90 days or 8 months following anti-TNF withdrawal, and S100A12 had modest
      predictive ability for flare within 30, 60, and 90 days. S100A12 levels at time
      of withdrawal and time to disease flare was inversely correlated (r=-0.36).
      CONCLUSION: Serum S100 levels did not predict maintenance of CID or disease
      flare, with S100A12 levels only moderately correlating inversely with time to
      disease flare. This article is protected by copyright. All rights reserved.

PMID- 30225951
TI  - Targeting dipeptidyl peptidase 8 genes inhibits proliferation, migration and
      invasion by inhibition of cyclin D1 and MMP2MMP9 signal pathway in cervical
      cancer.
AB  - BACKGROUND: DPP8 is a member of the dipeptidyl peptidase IV family, which belongs
      to the S9b protease subfamily. It regulates cell proliferation, apoptosis,
      migration and invasion during cancer progression. METHODS: To investigate the
      role of DPP8 in cervical cancer, we examined DPP8 levels in cervical cancer
      tissues and cells. The localization of DPP8 was determined by immunofluorescence
      staining. Subsequently, SiHa and HeLa cells were treated with small interfering
      RNA (siRNA)-DPP8. We used cell cycle analysis, an 5-ethyl-2'-deoxyuridine assay
      proliferation assay and a cellular apoptosis assay to determine the effect of
      DPP8 on the proliferation and apoptosis of cervical cancer cells. We used a
      Transwell assay to assess the number of transfection cancer cells migrating
      through the matrix. A real-time polymerase chain reaction and western blot
      analysis were used to analyze the expression of related proteins and to determine
      the phenotype caused by the depletion or overexpression of DPP8 in cervical
      cancer cells. RESULTS: We observed that DPP8 was highly expressed in cervical
      cancer tissues and cells. DPP8 expression was observed in the cytosol and in the
      perinuclear area, as well as in the nuclei of cervical cancer cells. Notably,
      when cells were treated with siRNA-DPP8, the expression of BAX increased, and the
      expression of cyclin D1, Bcl-2, MMP2 and MMP9 was downregulated. In cervical
      cancer cell lines, silencing the expression of DPP8 not only suppressed the
      proliferation, migration and invasion of the cervical cancer cells, but also
      promoted cervical cancer cell apoptosis. CONCLUSIONS: The data obtained in the
      present study reveal that DPP8 promotes the progression of cervical cancer.

PMID- 30225952
TI  - Psoriasiform skin eruption in a patient receiving certolizumab-pegol for
      ankylosing spondylitis: Report of a case and review of the literature.
AB  - Certolizumab-pegol is the first and only pegylated TNF-alpha antagonist approved
      in the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis
      and ankylosing spondylitis. We herein present a case of certolizumab-pegol
      induced generalized psoriasiform eruption in a patient with ankylosing
      spondylitis. The diagnosis was based on typical clinical and histopathological
      findings and further confirmed with Naranjo Adverse Drug Reaction Probability
      Scale which revealed a total score of nine supporting a definite causal
      relationship between the drug and skin eruption. As an important finding, a
      significant improvement of the generalized plaque lesions was achieved upon a
      therapy including high-potency topical corticosteroid and oral antihistamine
      without discontinuation of certolizumab-pegol. Moreover, we also present a
      literature review of the previously published cases with certolizumab-pegol
      induced psoriasiform eruption. Since all of these cases had Crohn's disease or
      rheumatoid arthritis as the underlying disease, this is the first case report of
      certolizumab-pegol induced psoriasiform eruption in a patient with ankylosing
      spondylitis, to the best of our knowledge.

PMID- 30225953
TI  - Hemolytic anemia potentially associated with aripiprazole.

PMID- 30225954
TI  - Evidence for Genetic Contribution to Variation in Post-Traumatic Osteoarthritis
      in Mice.
AB  - OBJECTIVE: Recombinant inbred (RI) mouse strains generated from a LG/J and SM/J
      intercross offer a unique resource to study complex genetic traits such as
      osteoarthritis (OA). We determined the susceptibility of 14 strains to various
      phenotypes characteristic of post-traumatic OA (PTOA). We hypothesize that
      phenotypic variability is associated with genetic variability. METHODS: 10-week
      old male mice underwent destabilization of the medial meniscus (DMM) to induce
      PTOA. Mice were sacrificed at 8-week post-surgery and knee joints were processed
      for histology to score cartilage degeneration and synovitis. Micro-CT was used to
      analyze trabecular bone parameters including subchondral bone plate thickness and
      synovial ectopic calcification. Gene expression in the knees was assessed by
      QuantiGene Plex assay. RESULTS: Broad-sense heritability ranged from 0.18-0.58
      suggesting that the surgical responses are moderately heritable. LGXSM-33, LGXSM
      5, LGXSM-46, and SM/J were highly susceptible to OA while LGXSM-131b, LGXSM-163,
      LGXSM-35, LGXSM-128a, and LG/J were relatively OA resistant. Our study allows,
      for the first time, the measurement of genetic correlations of phenotypes that
      are characteristic of PTOA: cartilage degeneration was significantly positively
      associated with synovitis (r = 0.83-0.91) and subchondral bone plate thickness
      was negatively correlated with ectopic calcification (r = -0.59). Moreover, we
      show that 40 of the 78 genes tested were significantly correlated with various
      (OA) phenotypes. Unlike the OA phenotypes, there was no evidence for genetic
      variation in differences in gene expression levels in DMM and SHAM knees.
      CONCLUSION: For these mouse strains, various characteristics of PTOA varied with
      genetic composition demonstrating a genetic basis for PTOA susceptibility. The
      heritability of PTOA was established. Phenotypes exhibited various degrees of
      correlations: (1) cartilage degeneration is positively correlated with synovitis,
      but (2) not with the formation of ectopic calcification. Further investigation of
      the regions of genome containing genes implicated in OA and expression data will
      be useful for studying mechanisms of OA and identifying therapeutic targets. This
      article is protected by copyright. All rights reserved.

PMID- 30225955
TI  - Transitional status and modifiable risk of frailty in Japanese older adults: A
      prospective cohort study.
AB  - AIM: The purpose of the present study was to identify risk factors for physical
      frailty and to understand the transitional status of frailty. METHODS: The
      participants were 4676 older adults in the National Center for Geriatrics and
      Gerontology - Study of Geriatric Syndromes. Physical frailty status was
      classified as robust, pre-frail and frail at baseline and 4-year follow up (mean
      follow up 47.9 +/- 1.8 months). Data for demographic variables, medical
      conditions, fall, depressive symptoms and cognitive function were also collected.
      Multiple imputation was used to reduce selection bias and loss of information.
      RESULTS: Progression occurred from a robust to frail status in 52 participants
      (2.6%) and from pre-frailty to frailty in 281 participants (12.0%). Mortality
      increased with frailty status at baseline: robust 46 (2.3%), pre-frail 112 (4.8%)
      and frail 54 (15.6%). In logistic regression analysis, age (OR 1.10, 95% CI 1.06
      1.13), sex (men; OR 0.67, 95% CI 0.46-0.95), body mass index (OR 1.06, 95% CI
      1.01-1.12]), fall (OR 1.92, 95% CI 1.31-2.81), Geriatric Depression Scale (OR
      1.15, 95% CI 1.08-1.22), Mini-Mental State Examination (OR 0.87, 95% CI 0.82
      0.93) and education (OR 0.91, 95% CI 0.85-0.98), were related with new incident
      frailty. Among participants in the pre-frail class at baseline, exhaustion (OR
      3.24, 95% CI 1.97-5.34), physical inactivity (OR 3.09, 95% CI 1.94-4.93), lower
      muscle strength (OR 3.77, 95% CI 2.35-6.03) and lower mobility (OR 2.54, 95% CI
      1.57-4.10) were related to progression to frailty (all P < 0.05). CONCLUSIONS:
      The results of the present prospective study provide key information on the
      transitional status of frailty and the risk factors for progression to frailty. A
      further study is required to determine the pathophysiological changes that
      underlie the transition to frailty. Geriatr Gerontol Int 2018; 18: 1562-1566.

PMID- 30225956
TI  - Is mild asymptomatic left ventricular systolic dysfunction always predictive of
      adverse events in high-risk populations? Insights from the DAVID-Berg study.
AB  - BACKGROUND: Mild asymptomatic left ventricular systolic dysfunction (ALVSD) may
      be associated with incident heart failure (HF). However, this gray zone group
      needs incremental risk refinement. We hypothesized that diastolic dysfunction
      (DD) may refine HF and death risk prediction in mild ALVSD. METHODS AND RESULTS:
      Among 4047 subjects aged >=55/<=80 years followed by 10 general practitioners in
      northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic
      outpatients at increased risk for HF. Baseline evaluation included clinical
      visit, N-terminal pro B-type natriuretic peptide, and echocardiogram. Based on
      left ventricular ejection fraction (LVEF) and DD, subjects were classified as:
      control group (normal LVEF, n = 459, 76%), mild ALVSD (LVEF >=40%/<53%) without
      DD (n = 89, 15%) and with DD (n = 54, 9%). Subjects with LVEF <40% or without
      full echocardiographic data were excluded from the analysis (n = 21). Mean age of
      the population was 69 +/-7 years, 56% were men, mostly hypertensive, mean LVEF
      was 61%. During a median follow-up of 5.7 years, 88 subjects (15%) experienced
      HF/death events (59 HF events and 29 deaths). Compared to the control group, mild
      ALVSD was associated with a higher risk of incident HF/death (hazard ratio 1.80,
      95% confidence interval 1.10-2.93, adjusted P = 0.019) according to the Cox
      proportional hazards model. However, this higher risk was present only in
      subjects with combined DD (P = 0.005) and not in those without it (P = 0.30).
      Results were consistent even considering the individual components of the primary
      outcome. CONCLUSION: In a high-risk population, an echocardiographic exam is
      normally performed to assess systolic dysfunction. Our data underline the
      importance of also relying on DD to risk stratify mild ALVSD. Mild ALVSD might be
      a predictor of adverse events mainly in subjects with combined DD, though further
      studies are needed to confirm these results.

PMID- 30225957
TI  - Prospective cohort trial to confirm the efficacy of no-touch radio frequency
      ablation.
AB  - BACKGROUND AND AIM: The aim of the present prospective study was to evaluate
      tumor recurrence (intrasubsegmental recurrence-free survival and local tumor
      recurrence-free survival) and hepatic functional reserve following no-touch
      ablation. METHODS: The prospective cohort study protocols were approved by the
      institutional ethics committee. All patients provided written, informed consent.
      Between January 2014 and September 2016, 231 patients with 277 hepatocellular
      carcinoma nodules were prospectively enrolled. An internally cooled bipolar
      electrode was used for no-touch ablation, while a monopolar electrode was used
      for direct puncture ablation. The intrasubsegmental recurrence-free survival rate
      was the primary end-point. The secondary outcomes were the local recurrence-free
      survival rate, the disease-free survival rate, and the changes in the Child-Pugh
      score. RESULTS: No-touch ablation resulted in significantly higher cumulative
      intrasubsegmental tumor recurrence-free survival rates than direct puncture
      ablation (98.0% vs 87.1% at 1 year, 96.9% vs 76.8% at 2 years, and 91.0% vs 68.3%
      at 3 years, P < 0.001). The no-touch group also showed significantly better local
      recurrence-free survival and disease-free survival. Even when only primary cases
      were analyzed, the same results were obtained. To adjust for differences in the
      background characteristics, inverse probability of treatment weighting adjustment
      was performed. Only intrasubsegmental tumor recurrence-free survival was
      significantly better in the no-touch group (hazard ratio [HR], 0.08; 95%
      confidence interval [CI], 0.02-0.20, P < 0.001); there was no difference in local
      tumor recurrence-free survival (HR, 0.36; 95% CI, 0.10-1.02, P = 0.071).
      CONCLUSIONS: No-touch ablation appears to be an ideal method for the prevention
      of intrahepatic dissemination.

PMID- 30225958
TI  - Characterising the Subsite Specificity of Urokinase-Type Plasminogen Activator
      and Tissue-Type Plasminogen Activator using a Sequence-Defined Peptide Aldehyde
      Library.
AB  - Urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator
      (tPA) are two serine proteases that contribute to initiating fibrinolysis by
      activating plasminogen. uPA is also an important tumour-associated protease due
      to its role in extracellular matrix remodelling. Overexpression of uPA has been
      identified in several different cancers and uPA inhibition has been reported as a
      promising therapeutic strategy. Although several peptide-based uPA inhibitors
      have been developed, the extent to which uPA tolerates different tetrapeptide
      sequences that span the P1-P4 positions remains to be thoroughly explored. In
      this study, we screened a sequence-defined peptide aldehyde library against uPA
      and tPA. Preferred sequences from the library screen yielded potent inhibitors
      for uPA, led by Ac-GTAR-H (Ki =18 nm), but not for tPA. Additionally, synthetic
      peptide substrates corresponding to preferred inhibitor sequences were cleaved
      with high catalytic efficiency by uPA but not by tPA. These findings provide new
      insights into the binding specificity of uPA and tPA and the relative activity of
      tetrapeptide inhibitors and substrates against these enzymes.

PMID- 30225959
TI  - Advanced heart failure: Trans-Atlantic perspectives on the Heart Failure
      Association of the European Society of Cardiology position statement.

PMID- 30225960
TI  - Prevalence and sociodemographic factors associated with depression among
      hospitalized patients with head and neck cancer-Results from a national study.
AB  - OBJECTIVE: Depression is a significant problem for patients with head and neck
      cancer (HNC). This study explored the prevalence of and sociodemographic and
      clinical factors associated with depression, among patients with HNC. METHODS: We
      performed a retrospective analysis of 71 541 cases of HNC using a national
      dataset, the Nationwide Inpatient Sample, from 2008 to 2013. Weighted,
      multivariate logistic regression analysis estimated association between
      sociodemographic/clinical factors and tumor anatomical site with diagnosis of a
      major depressive disorder. RESULTS: Overall prevalence of major depressive
      disorder in HNC was 9.3%; highest prevalence was found in patients with laryngeal
      cancer (28.5%). Compared with laryngeal cancer, there were lower odds of
      depression among patients with oral cavity cancer (adjusted odds ratio [aOR] =
      0.90; 95% CI, 0.84-0.97) and other anatomic sites (aOR = 0.87; 95% CI, 0.81
      0.94), except oropharyngeal cancer (aOR = 1.00; 95% CI, 0.93-1.08). For every
      unit increase in comorbidities, odds of depression increased by 20% (aOR = 1.20;
      95% CI, 1.19-1.23). Sociodemographic factors associated with increased odds of
      depression included being female (aOR = 1.77; 95% CI, 1.68-1.87), white (aOR =
      1.75; 95% CI, 1.59-1.92), and having Medicaid (aOR = 1.09; 95% CI, 1.01-1.19) or
      Medicare insurance (aOR = 1.19; 95% CI, 1.10-1.27). CONCLUSIONS: Depression odds
      vary depending on HNC anatomic site, and one in four patients with laryngeal
      cancer may be depressed. Since depression is prevalent in this survivor cohort,
      it is important that psychosocial assessment and intervention are integrated into
      mainstream clinical care for patients with HNC.

PMID- 30225961
TI  - Combined effects of four major geriatric syndromes on adverse outcomes based on
      Korean National Health Insurance claims data.
AB  - AIM: Geriatric syndromes are common among older individuals, and can affect their
      health and quality of life. The present study aimed to determine if combinations
      of geriatric syndromes affected adverse outcomes among older Koreans. METHODS:
      Korean national health insurance data were collected for a cohort of 5 058 720
      individuals who were aged >=65 years in 2008. The same data source was used to
      follow these individuals until 2015. Diagnostic codes were used to assess four
      major geriatric syndromes (delirium, fall-related fractures, incontinence and
      pressure ulcers) and adverse outcomes (mortality and nursing home
      institutionalization). RESULTS: The prevalence of geriatric syndromes was 0.3%
      for delirium, 3.49% for fall-related fractures, 1.08% for incontinence and 0.82%
      for pressure ulcers. All four geriatric syndromes were associated with increased
      risks of institutionalization (adjusted hazard ratio [aHR] 2.18, 95% CI 2.08-2.17
      for delirium; aHR 1.59, 95% CI 1.58-1.60 for fall-related fractures; aHR 1.43,
      95% CI 1.41-1.44 for incontinence; and aHR 2.51, 95% CI 2.47-2.55 for pressure
      ulcers) and increased risks of mortality (aHR 2.13, 95% CI 2.08-2.17 for
      delirium; aHR 1.41, 95% CI 1.40-1.42 for fall-related fractures; aHR 1.09, 95% CI
      1.07-1.10 for incontinence; and aHR 3.23, 95% CI 3.20-3.27 for pressure ulcers).
      The aHR for institutionalization were 1.64 (95% CI 1.63-1.65) for one geriatric
      syndrome, 2.40 (95% CI 2.35-2.44) for two coexisting geriatric syndromes and 2.56
      (95% CI 2.35-2.74) for three coexisting geriatric syndromes. The aHR for
      mortality were 1.52 (95% CI 1.51-1.53) for one geriatric syndrome, 2.36 (95% CI
      2.32-2.40) for two coexisting geriatric syndromes and 2.90 (95% CI 2.72-3.09) for
      three coexisting geriatric syndromes. CONCLUSIONS: Delirium, fall-related
      fractures, incontinence and pressure ulcers were associated with increased risks
      of institutionalization and mortality. The magnitude of these risks increased
      with increasing numbers of coexisting geriatric syndromes. Geriatr Gerontol Int
      2018; 18: 1463-1468.

PMID- 30225962
TI  - Nanopore-Based, Rapid Characterization of Individual Amyloid Particles in
      Solution: Concepts, Challenges, and Prospects.
AB  - Aggregates of misfolded proteins are associated with several devastating
      neurodegenerative diseases. These so-called amyloids are therefore explored as
      biomarkers for the diagnosis of dementia and other disorders, as well as for
      monitoring disease progression and assessment of the efficacy of therapeutic
      interventions. Quantification and characterization of amyloids as biomarkers is
      particularly demanding because the same amyloid-forming protein can exist in
      different states of assembly, ranging from nanometer-sized monomers to micrometer
      long fibrils that interchange dynamically both in vivo and in samples from body
      fluids ex vivo. Soluble oligomeric amyloid aggregates, in particular, are
      associated with neurotoxic effects, and their molecular organization, size, and
      shape appear to determine their toxicity. This concept article proposes that the
      emerging field of nanopore-based analytics on a single molecule and single
      aggregate level holds the potential to account for the heterogeneity of amyloid
      samples and to characterize these particles-rapidly, label-free, and in aqueous
      solution-with regard to their size, shape, and abundance. The article describes
      the concept of nanopore-based resistive pulse sensing, reviews previous work in
      amyloid analysis, and discusses limitations and challenges that will need to be
      overcome to realize the full potential of amyloid characterization on a single
      particle level.

PMID- 30225963
TI  - Commentary on Kertesz & Gordon (2018): Don't abandon opioid prescription control
      efforts, reform them.

PMID- 30225964
TI  - Empagliflozin reduces myocardial ketone utilization while preserving glucose
      utilization in diabetic hypertensive heart disease: A hyperpolarized 13 C
      magnetic resonance spectroscopy study.
AB  - AIM: To investigate the effects of the sodium-glucose co-transporter-2 inhibitor
      empagliflozin on myocardial ketone body utilization in diabetic, obese rats with
      spontaneously hypertensive heart failure (SHHF), after 6 months of treatment.
      MATERIALS AND METHODS: Myocardial ketone body utilization was measured in vivo
      real time using a novel ketone probe (hyperpolarized [3-13 C]acetoacetate) and
      magnetic resonance spectroscopy (MRS). Myocardial glucose utilization and cardiac
      function were also determined in vivo using hyperpolarized [1-13 C]pyruvate MRS
      and magnetic resonance imaging (MRI), respectively. Myocardial fatty acid uptake
      and liver ketogenesis were assessed via protein expression. RESULTS: At baseline,
      myocardial ketone and glucose utilization were both higher in SHHF compared with
      control rats. Six months of empagliflozin treatment in SHHF rats was associated
      with less obesity, lower blood pressure, reduced blood glucose and insulin
      levels, and increased fasting blood beta-hydroxybutyrate levels, as expected.
      Contrary to the hypothesis, myocardial ketone body utilization was lower in
      empagliflozin-treated SHHF rats, while glucose utilization and cardiac function
      were unaltered and hepatic congestion was reduced, compared with vehicle-treated
      SHHF rats. CONCLUSIONS: In diabetic hypertensive heart disease, empagliflozin
      reduces afterload without altering myocardial function and glucose utilization in
      the face of falling blood glucose levels, but does not enhance myocardial ketone
      utilization despite increased circulating levels.

PMID- 30225965
TI  - Global prevalence and disease burden of vitamin D deficiency: a roadmap for
      action in low- and middle-income countries.
AB  - Vitamin D is an essential nutrient for bone health and may influence the risks of
      respiratory illness, adverse pregnancy outcomes, and chronic diseases of
      adulthood. Because many countries have a relatively low supply of foods rich in
      vitamin D and inadequate exposure to natural ultraviolet B (UVB) radiation from
      sunlight, an important proportion of the global population is at risk of vitamin
      D deficiency. There is general agreement that the minimum serum/plasma 25
      hydroxyvitamin D concentration (25(OH)D) that protects against vitamin D
      deficiency-related bone disease is approximately 30 nmol/L; therefore, this
      threshold is suitable to define vitamin D deficiency in population surveys.
      However, efforts to assess the vitamin D status of populations in low- and middle
      income countries have been hampered by limited availability of population
      representative 25(OH)D data, particularly among population subgroups most
      vulnerable to the skeletal and potential extraskeletal consequences of low
      vitamin D status, namely exclusively breastfed infants, children, adolescents,
      pregnant and lactating women, and the elderly. In the absence of 25(OH)D data,
      identification of communities that would benefit from public health interventions
      to improve vitamin D status may require proxy indicators of the population risk
      of vitamin D deficiency, such as the prevalence of rickets or metrics of usual
      UVB exposure. If a high prevalence of vitamin D deficiency is identified (>20%
      prevalence of 25(OH)D < 30 nmol/L) or the risk for vitamin D deficiency is
      determined to be high based on proxy indicators (e.g., prevalence of rickets
      >1%), food fortification and/or targeted vitamin D supplementation policies can
      be implemented to reduce the burden of vitamin D deficiency-related conditions in
      vulnerable populations.

PMID- 30225966
TI  - Evidence-based physiotherapy clinical practice in the public health-care service
      in Ecuador.
AB  - OBJECTIVE: The aim of the study was to determine if evidence-based physiotherapy
      (EBP) was being applied in the public physiotherapy and physical rehabilitation
      departments in Ecuador, Zone 3. METHODS: A cross-sectional study was developed
      applying the "Evidence-Based Practice: Beliefs, Attitudes, Knowledge, and
      Behaviors of Physical Therapists" questionnaire, designed by Jette et al. and
      validated in Spanish by Guerra et al. to 67 physiotherapists working in the
      public service in the provinces of Chimborazo, Cotopaxi, Pastaza, and Tungurahua.
      RESULTS: Of the physiotherapists, 65.67% fully agree in being necessary to
      implement EBP in their clinical setting; however, 44.78% identified EBP as highly
      time demanding. Insufficient time (95.52%), lack of information resources
      (53.73%), and absence of support among co-workers (50.75%) were reported as the
      main barriers that prevent physiotherapists from practicing EBP. CONCLUSIONS:
      Physiotherapists showed a positive attitude and interest towards EBP, although
      there is unawareness on how to accomplish EBP on daily basis in addition to
      little specific training during preprofessional studies in relation to scientific
      research.

PMID- 30225967
TI  - Mineralocorticoid antagonism enhances brown adipose tissue function in humans: A
      randomized placebo-controlled cross-over study.
AB  - AIM: To investigate whether mineralocorticoid (MC) antagonism enhances brown
      adipose tissue (BAT) function in humans. MATERIALS AND METHODS: In a randomized
      double-blind, cross-over designed trial, 10 healthy adults (two men, eight women)
      underwent 2 weeks of spironolactone (100 mg/d) treatment and placebo, with an
      intervening 2-week wash-out period. BAT function was assessed in response to
      cooling and to a mixed meal. Metabolic activity was measured by fluoro
      deoxyglucose (FDG) uptake (maximal standardized uptake value, SUVmax ) using PET
      CT. Thermogenic activity was measured by skin temperatures overlying
      supraclavicular (SCL) BAT depots using infrared thermography. Postprandial
      metabolism was measured by energy production rate (EPR) and lipid synthesis using
      indirect calorimetry. RESULTS: During cooling, BAT metabolic activity (SUV 6.30
      +/- 2.16 vs 3.98 +/- 1.34; P < 0.05) and volume (54.9 +/- 22.8 vs 21.6 +/- 11.8
      cm3 ; P < 0.05) were significantly higher, and mean SCL temperature decreased by
      a smaller degree (-0.3 degrees C degrees +/- 0.2 degrees C vs -0.9 degrees C +/-
      0.2 degrees C; P = 0.05) with spironolactone treatment. A mixed meal increased
      SCL temperature and EPR. The postprandial rise in SCL temperature (+0.4 degrees C
      +/- 0.1 degrees C vs +0.1 degrees C +/- 0.1 degrees C; P < 0.05) but not in EPR
      was greater during spironolactone treatment. Postprandial lipid synthesis
      occurred in three participants with placebo but in none with spironolactone
      treatment (P = 0.06). CONCLUSION: MC antagonism enhanced human BAT function in
      response to cooling and to a meal during which lipid synthesis was suppressed. As
      postprandial EPR comprises energy dissipated as heat and energy required to store
      nutrients, the reduction in lipid synthesis during MC antagonism is a probable
      consequence of concurrent stimulation of BAT thermogenesis. The shift in energy
      usage from storage to heat dissipation indicates that MC antagonists may have
      therapeutic benefit for obesity.

PMID- 30225968
TI  - IEPA 11th International Conference on Early Intervention in Mental Health 
      "Prevention and Early Intervention: Broadening the Scope" Boston, Massachusetts,
      USA, 7-10 October 2018.

PMID- 30225970
TI  - Pain location and widespread pain in youth with orthopedic conditions:
      Methodological and statistical issues on reliability analysis.
AB  - We were interested to read the recent paper by Foxen-Craft E and colleagues
      published online in Jul 2018 in the Eur J Pain. (Foxen et al., 2018). The authors
      aimed to explore the reliability and validity of a pain body map among youth with
      orthopedic conditions before surgery. Youth ages 10-17 years completed the body
      map and other self-reported outcomes at their preoperative clinic visit and at
      their day of surgery. Percent agreement and Kappa statistics were used to examine
      the discrepancy of children's pain location reports between baseline and second
      assessments This article is protected by copyright. All rights reserved.

PMID- 30225969
TI  - Fast Magic-Angle Spinning 19 F NMR Spectroscopy of HIV-1 Capsid Protein
      Assemblies.
AB  - 19 F NMR spectroscopy is an attractive and growing area of research with broad
      applications in biochemistry, chemical biology, medicinal chemistry, and
      materials science. We have explored fast magic angle spinning (MAS) 19 F solid
      state NMR spectroscopy in assemblies of HIV-1 capsid protein. Tryptophan residues
      with fluorine substitution at the 5-position of the indole ring were used as the
      reporters. The 19 F chemical shifts for the five tryptophan residues are
      distinct, reflecting differences in their local environment. Spin-diffusion and
      radio-frequency-driven-recoupling experiments were performed at MAS frequencies
      of 35 kHz and 40-60 kHz, respectively. Fast MAS frequencies of 40-60 kHz are
      essential for consistently establishing 19 F-19 F correlations, yielding
      interatomic distances of the order of 20 A. Our results demonstrate the potential
      of fast MAS 19 F NMR spectroscopy for structural analysis in large biological
      assemblies.

PMID- 30225971
TI  - Ultrasound elastography is useful to distinguish acute and chronic deep vein
      thrombosis.
AB  - Essentials Ultrasound elastography uses tissue deformation to assess the relative
      quantification of its elasticity. Compression and duplex ultrasonography may be
      unable to correctly determine the thrombus age. Ultrasound elastography may be
      useful to distinguish between acute and chronic deep vein thrombosis. The exact
      determination of the thrombus age could have both therapeutic and prognostic
      implications. BACKGROUND: Background Ultrasound elastography (UE) imaging is a
      novel sonographic technique that is commonly employed for relative quantification
      of tissue elasticity. Its applicability to venous thromboembolic events has not
      yet been fully established; in particular, it is unclear whether this technique
      may be useful in determining the age of deep vein thrombosis (DVT). Thus, the aim
      of this study was to assess the role of UE in distinguishing acute from chronic
      DVT. Methods Consecutive patients with a first unprovoked acute and chronic (3
      months old) DVT of the lower limbs were analyzed. Patients with recurrent DVT or
      with a suspected recurrence were excluded. The mean elasticity index (EI) values
      of acute and chronic popliteal and femoral vein thrombosis were compared. The
      accuracy of the EI in distinguishing acute from chronic DVT was also assessed by
      measuring the sensitivity, specificity, positive and negative predictive values,
      and likelihood ratios. Results One-hundred and forty-nine patients (mean age 63.9
      years, standard deviation 13.6; 73 males) with acute and chronic DVT were
      included. The mean EI of acute femoral DVT was higher than that of chronic
      femoral DVT (5.09 versus 2.46), and the mean EI of acute popliteal DVT was higher
      than that of chronic popliteal DVT (4.96 versus 2.48). An EI value of > 4
      resulted in a sensitivity of 98.9% (95% confidence interval [CI] 93.3-99.9), a
      specificity of 99.1% (95% CI 94.8-99.9), a positive predictive value of 91.1%
      (95% CI 77.9-97.1), a negative predictive value of 98.6% (95% CI 91.3-99.9), a
      positive likelihood ratio of 13.23 (95% CI 93-653) and a negative likelihood
      ratio of 0.001 (95% CI 0.008-0.05) for acute DVT. Conclusions UE appears to be a
      promising technique for distinguishing between acute and chronic DVT. Larger
      prospective studies are warranted to confirm our preliminary findings.

PMID- 30225972
TI  - ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management
      of monogenic diabetes in children and adolescents.

PMID- 30225974
TI  - Pd-catalyzed Oxidative Cross-coupling of Alkyl Chromium(0) Fischer Carbene
      Complexes with Organoboronic Acids.
AB  - Alkyl chromium(0) carbene complexes have been explored as the cross-coupling
      partners in the palladium-catalyzed reaction with aryl or alkenyl boronic acids.
      This coupling reaction displays the versatile reactivities of alkyl chromium(0)
      carbenes under palladium catalysis. Mechanistically, this transformation is
      proposed to involve deprotonation of the alkyl chromium carbene substrate to
      generate a vinyl chromium anion intermediate that undergoes transmetalation to
      organopalladium species and reductive elimination.

PMID- 30225973
TI  - Insight into selective mechanism of class of I-BRD9 inhibitors toward BRD9 based
      on molecular dynamics simulations.
AB  - Recently, bromodomain-containing protein 9 (BRD9), 7 (BRD7), and 4 (BRD4) have
      been potential targets of anticancer drug design. Molecular dynamic simulations
      followed by molecular mechanics Poisson-Boltzmann surface area calculation were
      performed to study the selective mechanism of I-BRD9 inhibitor H1B and its
      derivatives N1D, TVU, and 5V2 toward BRD9 and BRD4. The rank of our calculated
      binding free energies agrees with that of the experimental data. The results show
      that binding free energy of H1B to BRD7 is slightly lower than that of H1B to
      BRD9, and all four inhibitors bind more tightly to BRD9 than to BRD4.
      Decomposition of binding free energies into individual residues implies that
      Ile164 and Asn211 in BRD7 and Ile53 and Asn100 in BRD9 play a significant role in
      the selectivity of H1B toward BRD7 and BRD9. Besides, several key residues Phe44,
      Ile53, Asn100, Thr104 in BRD9 and Pro82, Lys91, Asn140, Asp144 in BRD4 that are
      located in the ZA-loop and BC-loop provide significant contributions to binding
      selectivity of inhibitors to BRD9 and BRD4. This study is expected to provide
      important theoretical guidance for rational designs of highly selective
      inhibitors targeting BRD9 and BRD4.

PMID- 30225975
TI  - Intrahepatic recurrence of single nodular hepatocellular carcinoma after surgical
      resection: an analysis by segmental distribution.
AB  - BACKGROUND: Intrahepatic recurrence is the major cause of management failure
      after surgical resection of hepatocellular carcinoma (HCC). In the present study,
      we analysed intrahepatic recurrence by HCC distribution using Couinaud's liver
      segments. METHODS: Recurrence proximity levels were defined with respect to
      primary tumour locations from Level LR (locoregional) to Level IV. Initial and
      recurrent tumours were compared with segmental distribution of their locations,
      and recurrence proximity levels were compared with initial tumour locations and
      disease-free survival. RESULTS: Eighty-five (58.2%) of 146 patients with single
      nodular HCC experienced intrahepatic recurrence after surgical resection with a
      mean disease-free survival of 20.8 +/- 21.1 months. Segmental distributions of
      initial and recurrent tumour locations were not significantly different (P >
      0.05), and both were similar to the normal segmental volume distribution except
      segments S5, S6 and S8. Recurrences in proximity levels LR to IV were 11.1%,
      34.9%, 25.4%, 21.4%, and 7.1%, respectively, and this distribution agreed well
      with theoretical proximity level distribution (P > 0.05). Disease-free survivals
      for different recurrence levels were not different (P = 0.530). CONCLUSION:
      Intrahepatic recurrences after surgical resection of single nodular HCC occurred
      evenly in the remnant liver, and the timing was independent of the proximity
      between initial and recurrent tumours. Prevention was found to be proportional to
      the amount of liver segments removed. Surgical plans should take this into
      consideration.

PMID- 30225976
TI  - Safety and efficacy of a novel high-intensity focused electromagnetic technology
      device for noninvasive abdominal body shaping.
AB  - BACKGROUND: Thermal fat reduction technologies are leading the market for
      nonsurgical abdominal contouring. However, they are ideal principally for
      patients with fat bulges. OBJECTIVES: Our study investigates the effects of a
      novel nonthermal technology affecting the abdominal musculature and subcutaneous
      adipose tissue. MATERIALS AND METHODS: A total of 22 patients (avg. BMI 23.8 kg m
      2 ) underwent 4 treatments on abdomen with high-intensity focused electromagnetic
      (HIFEM) field device. Treatments took 30 minutes and were spaced apart by 2-3
      days. Photographs, weight, and waist measurements were taken at the baseline,
      after the last treatment, and at month 3 follow-up. Patient satisfaction was
      noted. Photographs were evaluated by blinded evaluators. RESULTS: The study
      protocol was completed by 19 patients. At month 3, the average waist size
      reduction was 4.37 +/- 2.63 cm (P < 0.01). The evaluators identified the before
      image from the 3-month image 89.47% of the time. About 91% of patients reported
      their abdominal appearance improved, and 92% stated they are satisfied with
      treatment results at month 3. No adverse events occurred. CONCLUSION: Observed
      waist size reduction and aesthetic improvement appear to be a combination of fat
      reduction and increased muscle definition of abdominal wall. In lower BMI
      patients, the increased abdominal muscle definition was largely responsible for
      the improvement. This novel energy device provides an additional tool for body
      contouring with primary application for lower and medium BMI patients.

PMID- 30225977
TI  - The novel HLA-DRB3*02:02:11 allele identified in an Italian individual.
AB  - HLA-DRB3*02:02:11 differs from HLA-DRB3*02:02:01:01 by a single synonymous
      substitution in exon 3'.

PMID- 30225978
TI  - Efficacy and safety of short-term dual antiplatelet therapy (<=6 months) after
      percutaneous coronary intervention for acute coronary syndrome: A systematic
      review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Patients who undergo percutaneous coronary intervention (PCI) for
      acute coronary syndrome (ACS) are at increased risk for subsequent ischemic
      events. HYPOTHESIS: Short-term dual antiplatelet therapy (DAPT) (<=6 months) is
      inferior to standard or long-term DAPT in patients who undergo PCI for ACS
      events. METHODS: We conducted a systematic review and meta-analysis of randomized
      controlled trials that compared short-term (<=6 months) to long-term (>=12
      months) DAPT after PCI for ACS. We searched MEDLINE, EMBASE, SCOPUS, and the
      Cochrane Central Register of Controlled Trials database. RESULTS: Ten randomized
      controlled trials, including a total of 12 696 patients, met our inclusion
      criteria. For short-term DAPT, duration of therapy ranged from 3 to 6 months,
      while long-term DAPT ranged from 12 to 24 months. The majority of studies used
      clopidogrel and second-generation drug-eluting stents. No statistically
      significant difference was found between short-term and long-term DAPT with
      regard to myocardial infarction (odds ratio 1.21; 95% confidence interval 0.94
      1.57; P = 0.14), stent thrombosis (odds ratio 1.54; 95% confidence interval 1.00
      2.38; P = 0.052), or major bleeding events (odds ratio 0.74; 95% confidence
      interval 0.49-1.11; P = 0.14). There was no significant difference in all-cause
      mortality, cardiac death, or net adverse cardiac and cerebrovascular events.
      CONCLUSIONS: Our meta-analysis demonstrated that short-term DAPT (<6 months)
      after PCI for ACS was not associated with increased risk of myocardial infarction
      or stent thrombosis when compared to long-term DAPT.

PMID- 30225979
TI  - Interactions between the ACT Domains and Catalytic Subunits of Acetohydroxyacid
      Synthases (AHASs) from Different Species.
AB  - Acetohydroxyacid synthase (AHAS), which catalyzes the first step in the
      biosynthesis of branched-chain amino acids, is a target of several types of
      potent herbicides and antimicrobials. AHAS contains the catalytic subunit (CS)
      and the regulatory subunit (RS). The AHAS RS is usually composed of ACT domains
      and C-terminal domains. Herein, it is reported that the ACT domain of AHAS RS
      from different species could efficiently activate its respective CS. Moreover,
      the universal cross-activation between the CSs and the ACT domains of RSs across
      species has been discovered. Based on these biochemical and structural analyses,
      a molecular basis for the universal ACT-triggered CS activation is proposed,
      which would help to design broad-spectrum herbicides by targeting the interaction
      interface between CS and ACT from different species.

PMID- 30225980
TI  - Three-dimensional electron microscopy techniques for unravelling mitochondrial
      dysfunction in heart failure and identification of new pharmacological targets.
AB  - A hallmark of heart failure is mitochondrial dysfunction leading to a
      bioenergetics imbalance in the myocardium. Consequently, there is much interest
      in targeting mitochondrial abnormalities to attenuate the pathogenesis of heart
      failure. This review discusses (i) how electron microscopy (EM) techniques have
      been fundamental for the current understanding of mitochondrial structure
      function, (ii) the paradigm shift in resolutions now achievable by 3-D EM
      techniques due to the introduction of direct detection devices and phase plate
      technology, and (iii) the application of EM for unravelling mitochondrial
      pathological remodelling in heart failure. We further consider the tremendous
      potential of multi-scale EM techniques for the development of therapeutics,
      structure-based ligand design and for delineating how a drug elicits
      nanostructural effects at the molecular, organelle and cellular levels. In
      conclusion, 3-D EM techniques have entered a new era of structural biology and
      are poised to play a pivotal role in discovering new therapies targeting
      mitochondria for treating heart failure.

PMID- 30225981
TI  - 'Ripple' effect on infant zBMI trajectory of an internet-based weight loss
      program for low-income postpartum women.
AB  - BACKGROUND: Weight loss interventions can have positive 'ripple' effects on
      untreated partners in the home, but ripple effects on infants are unknown.
      OBJECTIVE: To examine whether a 12-month internet-based weight loss intervention
      for postpartum mothers had a positive ripple effect on participants' infants.
      METHODS: A 12-month cluster randomized, assessor-blind, clinical trial enrolling
      371 postpartum women at 12 Women, Infants, Children clinics in CA. Clinics were
      randomized to standard Women, Infants, Children or an internet-based weight loss
      intervention for mothers. RESULTS: A total of 333 of the 371 (89.8%) mothers
      assented for infant participation. Infants were 5.3 +/- 3.2 months; 75.9% were
      Hispanic and 64% were breastfeeding. Infant retention was 272/333 (82.7%) at 6
      months post enrollment and 251/333 (75.3%) at 12 months post enrollment. In
      intent-to-treat analysis, a significant interaction between group and time was
      observed (p = 0.008) with the offspring of intervention mothers exhibiting lower
      zBMI change from study entry through 6 months (0.23 [CI, 0.03, 0.44] vs. 0.65
      [0.50, 0.79] zBMI change, respectively; p = 0.001) but was not significant
      through 12 months (p = 0.16). Regardless of group, maternal reports at the final
      assessment indicated that infants (aged =17.2 +/- 3.4 months) consumed sweetened
      beverages (0.93 +/- 1.5/week), juice (2.0 +/- 1.4/day), 'junk food' (7.8 +/-
      5.4/week) and fast food (2/month), and 46.7% of the infants had a TV in their
      bedroom. CONCLUSIONS: An internet-based weight loss program for low-income,
      postpartum mothers had a positive 'ripple' effect on the zBMI of infants in the
      home during the first 6 months of treatment.

PMID- 30225982
TI  - Intake, sources, and determinants of free sugars intake in Australian children
      aged 12-14 months.
AB  - The consumption of free sugars is directly associated with adiposity and dental
      caries in early childhood; however, intake data in the first 2 years of life are
      limited. This cross-sectional analysis aims to identify major food sources of
      free sugars for Australian children aged 12-14 months and investigate factors
      associated with meeting the World Health Organisation (WHO) Guideline for sugars
      intake. Three days of nonconsecutive dietary data were collected via a 24-hr
      recall and 2-day food record for 828 participants. Usual intake of energy, total
      sugars, and free sugars were estimated, along with food group contributions to
      free sugars. Multiple logistic regression analysis was used to investigate
      factors associated with exceeding the WHO conservative recommendation that <5% of
      energy should come from free sugars. Mean free sugars intake was 8.8 (SD 7.7, IQR
      3.7-11.6) g/day, contributing 3.6% (SD 2.8, IQR 1.6-4.8) of energy. Only 2.4% of
      participants exceeded the WHO recommendation that <10% of energy should come from
      free sugars, with 22.8% of participants exceeding the <5% recommendation.
      Children from households with greater socio-economic disadvantage (IRSAD <5, OR =
      1.94) and in the lowest income bracket (OR = 2.10) were more likely to have
      intakes >=5% of energy. Major food sources of free sugars were commercial infant
      foods (26.6%), cereal-based products (19.7%), namely, sweet biscuits (8.3%) and
      cakes (7.6%), followed by yoghurt (9.6%), and fruit and vegetable beverages
      (7.4%). These findings highlight the substantial contribution of infant foods to
      free sugars intakes and provide further evidence that dietary intakes are
      influenced by social determinants.

PMID- 30225983
TI  - Gastrointestinal: Endoscopic findings of monomorphic epitheliotropic intestinal T
      cell lymphoma.

PMID- 30225984
TI  - Activity-dependent central nervous system myelination throughout life.
AB  - Myelin, the multilayered membrane surrounding many axons in the nervous system,
      increases the speed by which electrical signals travel along axons and
      facilitates neuronal communication between distant regions of the nervous system.
      However, how neuronal signals influence the myelinating process in the CNS is
      still largely unclear. Recent studies have significantly advanced this
      understanding, identifying important roles for neuronal activity in controlling
      oligodendrocyte development and their capacity of producing myelin in both
      developing and mature CNS. Here, we review these recent advances, and discuss
      potential mechanisms underpinning activity-dependent myelination and how
      remyelination may be stimulated via manipulating axonal activity, raising new
      questions for future research.

PMID- 30225985
TI  - Efficacy of Botulinum Toxin A for Treating Cramps in Diabetic Neuropathy.
AB  - OBJECTIVE: Muscle cramps occur in >50% of diabetic patients and reduce the
      quality of life. No effective treatment is available. We evaluated the clinical
      effectiveness of botulinum toxin A (BTX-A) injections for treating cramps in
      diabetic patients with neuropathy. METHODS: This single-center, double-blind,
      placebo-controlled perspective study investigated the efficacy and safety of BTX
      A intramuscular injection for treating calf or foot cramps refractory to common
      pharmacological drugs. Fifty diabetic patients with peripheral neuropathy and
      cramps were randomly assigned to 2 matched groups. BTX-A (100 or 30 units) or
      saline was injected on each side into the gastrocnemius or the small flexor foot
      muscles. Changes in pain intensity (primary outcome) and cramp frequency were
      evaluated over the course of 20 weeks after BTX-A administration. Cramp
      interference in daily life and the electrophysiological cramp threshold frequency
      were also measured. The treatment was repeated 5 months after first injection in
      19 responders. RESULTS: All outcome measures improved significantly after BTX-A
      compared with placebo. The changes with respect to baseline were already
      significant after 1 week and persisted up to week 14. Only 5 of 25 (20%) patients
      were nonresponders (<50% decrease of the primary outcome). The responses to a
      second BTX-A injection provided results similar to the first administration. Mild
      pain at the injection site (4/25 cases) was the only adverse event, and it
      disappeared within 2 to 3 days. INTERPRETATION: Local BTX-A infiltration is an
      efficacious and safe procedure for obtaining a sustained amelioration of muscle
      cramps associated with diabetic neuropathy. Ann Neurol 2018;84:682-690.

PMID- 30225986
TI  - Impaired histaminergic neurotransmission in children with narcolepsy type 1.
AB  - OBJECTIVE: Narcolepsy is a sleep disorder characterized in humans by excessive
      daytime sleepiness and cataplexy. Greater than fifty percent of narcoleptic
      patients have an onset of symptoms prior to the age of 18. Current general
      agreement considers the loss of hypothalamic hypocretin (orexin) neurons as the
      direct cause of narcolepsy notably cataplexy. To assess whether brain histamine
      (HA) is also involved, we quantified the cerebrospinal fluid (CSF) levels of HA
      and tele-methylhistamine (t-MeHA), the direct metabolite of HA between children
      with orexin-deficient narcolepsy type 1 (NT1) and controls. METHODS: We included
      24 children with NT1 (12.3 +/- 3.6 years, 11 boys, 83% cataplexy, 100% HLA
      DQB1*06:02) and 21 control children (11.2 +/- 4.2 years, 10 boys). CSF HA and t
      MeHA were measured in all subjects using a highly sensitive liquid
      chromatographic-electrospray/tandem mass spectrometric assay. CSF hypocretin-1
      values were determined in the narcoleptic patients. RESULTS: Compared with the
      controls, NT1 children had higher CSF HA levels (771 vs 234 pmol/L, P < 0.001),
      lower t-MeHA levels (879 vs 1924 pmol/L, P < 0.001), and lower t-MeHA/HA ratios
      (1.1 vs 8.2, P < 0.001). NT1 patients had higher BMI z-scores (2.7 +/- 1.6 vs 1.0
      +/- 2.3, P = 0.006) and were more often obese (58% vs 29%, P = 0.05) than the
      controls. Multivariable analyses including age, gender, and BMI z-score showed a
      significant decrease in CSF HA levels when the BMI z-score increased in patients
      (P = 0.007) but not in the controls. No association was found between CSF HA, t
      MeHA, disease duration, age at disease onset, the presence of cataplexy, lumbar
      puncture timing, and CSF hypocretin levels. CONCLUSIONS: Narcolepsy type 1
      children had a higher CSF HA level together with a lower t-MeHA level leading to
      a significant decrease in the t-MeHA/HA ratios. These results suggest a decreased
      HA turnover and an impairment of histaminergic neurotransmission in narcoleptic
      children and support the use of a histaminergic therapy in the treatment against
      narcolepsy.

PMID- 30225987
TI  - Photocatalytic Performance of H6 P2 W18 O62 /TiO2 Nanocomposite Encapsulated into
      Beta Zeolite under UV Irradiation in the Degradation of Methyl Orange.
AB  - In this work, neat and supported H6 P2 W18 O62 into nanocage of beta-zeolite were
      synthesized. However, H6 P2 W18 O62 into nanocage of beta-zeolite was synthesized
      via template synthesis method. In addition, TiO2 was supported on H6 P2 W18 O62
      /beta zeolite by impregnation method. The obtained materials were characterized
      by XRD, FT-IR, UV-Vis, FESEM and EDS techniques. Also, W and Ti contents of the
      catalyst were determined by ICP and EDS technique. The results reveal that the
      photocatalyst performance depends on catalyst loading, pH effect, and methyl
      orange concentration. Photocatalytic degradation of methyl orange follows a
      pseudo-first order kinetic. The chemical oxygen demand (COD) experimental proved
      mineralization of methyl orange. Another reason for degradation and
      mineralization of methyl orange is the absence of hydrazine at the end of
      reaction which is one of the photodecolorization products. The plausible
      mechanism for photodegradation of MO was proposed.

PMID- 30225988
TI  - Effects of combined treatment with blood flow restriction and low-intensity
      electrical stimulation on diabetes mellitus-associated muscle atrophy in rats.
AB  - BACKGROUND: Diabetes mellitus (DM) results in decreased muscle mass and harmful
      complications. Blood flow restriction (Bfr) and electrical stimulation (ES)
      increase muscle protein synthesis. We hypothesized that combined Bfr and low
      intensity ES may be more effective in preventing diabetes-associated muscle
      atrophy by inhibiting the downregulation of protein synthesis-related pathways.
      In this study, the effects of combined Bfr and low-intensity ES on diabetes
      associated muscle atrophy were investigated by evaluating advanced glycation end
      products (AGEs) and receptor for AGEs (RAGE) in rats. METHODS: Twenty-four Goto
      Kakizaki (GK) rats were randomly divided into four treatment groups: sedentary
      DM, DM + Bfr (pressure cuffs placed around the thigh), DM + ES, and DM + Bfr +
      ES. Six Wistar rats were used as an age-matched control. Levels of AGEs and the
      expression of RAGE, extracellular signal-regulated kinase (ERK), and ribosomal
      protein S6 (rpS6) were determined in plantaris muscles. RESULTS: Diabetes
      resulted in a loss of muscle mass and upregulation of AGEs and RAGE in the
      plantaris muscle compared with the control group. Treatment with Bfr and ES alone
      failed to attenuate diabetes-associated loss of muscle mass, and could not
      prevent the upregulation of AGEs. However, the combination of Bfr and ES
      prevented the diabetes-associated decrease in muscle mass and upregulation of
      AGEs. In addition, the combination treatment prevented diabetes-associated
      decreases in the expression of phosphorylated rpS6. CONCLUSIONS: Combination
      treatment with Bfr and ES may prevent diabetes-associated muscle atrophy by
      upregulating inhibition of AGEs, which leads to the activation of protein
      synthesis.

PMID- 30225989
TI  - A systematic review of cognitive behavioural therapy for anxiety in adults with
      intellectual disabilities.
AB  - BACKGROUND: Anxiety disorders have high prevalence in people with intellectual
      disabilities. In populations without intellectual disabilities, cognitive
      behavioural therapy is a first line psychological therapy for these
      presentations. There is no existing review of the range of methods and outcomes
      from intervention studies in this area. METHOD: A systematic review was carried
      out following guidance in the Cochrane handbook for systematic reviews of
      interventions. RESULTS: Nineteen studies were identified. The majority of reports
      were descriptive case studies; the most frequently described presentations were
      non-specific anxiety disorders and post-traumatic stress disorder; the most
      frequently described cognitive techniques were psycho-education and interventions
      directly aimed at thoughts and beliefs and most studies reported positive
      outcomes, although the better controlled studies tended to report less
      comprehensive impacts. CONCLUSIONS: A range of presentations have been described
      although the area is still at a primarily descriptive stage. We discuss
      intervention structures and approaches that require further research.

PMID- 30225991
TI  - HLA-A, -B, -DRB1, -DQA1, and -DQB1 profile in a population from southern Brazil.
AB  - The aim of this study was to determine the allele and haplotype frequencies of
      HLA-A, -B, -DRB1, and -DQB1 in a self-declared White population from the north
      and northwestern state of Parana, southern Brazil, and compare the data with
      populations worldwide. The genotyping was performed with a group of 641
      individuals, based on PCR-SSO and -SSP methods, and allele and haplotype
      frequencies were estimated. Comparisons with European, African, Asian, and
      Amerindian populations were performed. The most frequent allelic groups, alleles
      and haplotypes were: HLA-A*02, HLA-B*35, HLA-DRB1*07:01, HLA-DQB1*03:01, and HLA
      A*01/B*08/DRB1*03:01. The results reinforced a predominance of a European
      composition in the self-declared White population from the north and northwestern
      Parana.

PMID- 30225992
TI  - Three Multicenter, Randomized, Double-Blind, Placebo-Controlled Studies
      Evaluating the Efficacy and Safety of Ustekinumab in Axial Spondyloarthritis.
AB  - OBJECTIVES: The efficacy and safety of ustekinumab were evaluated in 3
      randomized, placebo-controlled studies in patients with axial spondyloarthritis
      (axSpA). The first 2 studies included patients with radiographic axSpA (Study 1
      [anti-tumor necrosis factor (TNF)-naive]; Study 2 [anti-TNF refractory]), and
      Study 3 patients had non-radiographic axSpA. METHODS: In all 3 studies, patients
      were randomly assigned (1:1:1) to receive subcutaneous ustekinumab 45mg or 90mg
      or placebo up to 24 weeks, after which placebo-treated patients were rerandomized
      to receive ustekinumab 45mg or 90mg. The primary endpoint in Studies 1 and 2 was
      40% improvement on Assessment of SpondyloArthritis international Society
      (ASAS40); for Study 3, it was 20% ASAS improvement (ASAS20). Other disease
      activity and safety measures were also evaluated. A Week 24 analysis of Study 1
      was pre-planned to determine continuation of Studies 2 and 3. RESULTS: For Study
      1, primary and major secondary endpoints were not met, and the study was
      discontinued. As a result, Studies 2 and 3 were prematurely discontinued before
      they were fully enrolled. For all 3 studies, neither ustekinumab dose group
      demonstrated clinically meaningful improvement over placebo on key efficacy
      endpoints. The proportion of patients experiencing adverse events in the
      ustekinumab groups was consistent with those in previous studies. CONCLUSIONS: In
      these 3 placebo-controlled trials, efficacy of ustekinumab in the treatment of
      axSpA was not demonstrated. The safety profile was consistent with that of
      studies in other indications. This article is protected by copyright. All rights
      reserved.

PMID- 30225990
TI  - Sex-related differences in left ventricular diastolic function and arterial
      elastance during admission in patients with heart failure with preserved ejection
      fraction: The PURSUIT HFpEF study.
AB  - BACKGROUND: We previously reported that an index of afterload-related left
      ventricular diastolic function, operant diastolic elastance (Ed)/effective
      arterial elastance (Ea) = E/e'/(0.9 * systolic blood pressure), was significantly
      higher in elderly hypertensive women. We aimed to determine sex-related
      differences in the E/e'-related indices for left ventricular diastolic function
      and their related factors during admission in patients with heart failure with
      preserved ejection fraction (HFpEF). HYPOTHESIS: Elderly HFpEF women exhibit
      severe left ventricular diastolic dysfunction associated with different left
      atrioventricular volume ratio. METHODS: We divided 267 patients with HFpEF
      (men/women, 116/151) into two groups by age (>=75 years, n = 212; <75 years, n =
      55). We examined the alterations of E/e', E/e'/stroke volume index = Ed, and
      Ed/Ea, and cardiac structure during admission. RESULTS: Ed and Ea were
      significantly higher in women than in men, at admission, especially in patients
      >=75 years. Before discharge, not only Ed and Ea but also Ed/Ea was significantly
      higher in women than in men, especially in patients >=75 years. Elderly female
      patients had larger left atrial than left ventricular volume. CONCLUSIONS: Higher
      afterload-related left ventricular diastolic elastance, Ed/Ea, in association
      with higher arterial elastance, Ea, accompanied by left atrioventricular volume
      mismatch was observed in elderly HFpEF women.

PMID- 30225993
TI  - Identification of the novel HLA-DPA1*01:03:01:12 allele in a Saudi individual.
AB  - HLA-DPA1*01:03:01:12 differs from HLA-DPA1*01:03:01:01 by a single nucleotide
      substitution (G -> C) at position 4239.

PMID- 30225994
TI  - Automatic detection of significant areas for functional data with directional
      error control.
AB  - In this paper, we propose a large-scale multiple testing procedure to find the
      significant sub-areas between two samples of curves automatically. The procedure
      is optimal in that it controls the directional false discovery rate at any
      specified level on a continuum asymptotically. By introducing a nonparametric
      Gaussian process regression model for the two-sided multiple test, the procedure
      is computationally inexpensive. It can cope with problems with multidimensional
      covariates and accommodate different sampling designs across the samples. We
      further propose the significant curve/surface, giving an insight on dynamic
      significant differences between two curves. Simulation studies demonstrate that
      the proposed procedure enjoys superior performance with strong power and good
      directional error control. The procedure is also illustrated with the application
      to two executive function studies in hemiplegia.

PMID- 30225995
TI  - Fe-based Metallic Glasses in Functional Catalytic Applications.
AB  - With an intrinsically disordered atomic structure and a widely tunable atomic
      constituent, metallic glasses (MGs) have been extensively studied as promising
      catalysts in different catalytic fields. Particularly, Fe-based MGs with high
      catalytic activity, relatively low material cost, and environmental friendly
      compatibility also emerge as advanced catalysts. This review systematically
      discusses the recent advances of Fe-based MGs in catalytic applications,
      including wastewater remediation based on reductive degradation by multicomponent
      Fe-based MGs, oxidative degradation by introduction of advanced oxidation
      processes (AOPs) and nanocrystallization applied in Fe-based MGs up to date, and
      renewable energy conversion, with purposes of revealing Fe-based MG catalysts in
      the further improvement of catalytic performance and exploiting their promising
      catalytic abilities in a widely catalytic field.

PMID- 30225996
TI  - Full manuscript title: Early subungual melanoma: A diagnostic and treatment
      challenge.

PMID- 30225997
TI  - Novel bioactive peptides demonstrating anti-dengue virus activity isolated from
      the Asian medicinal plant Acacia Catechu.
AB  - The therapeutic activities of food-derived bioactive proteins and peptides are
      attracting increased attention within the research community. Medicinal plants
      used in traditional medicines are an excellent source of bioactive proteins and
      peptides, especially those traditionally prepared by water extraction for use as
      tea or food supplement. In this study, novel bioactive peptides were isolated
      from enzymatic digests of 33 Thai medicinal plants. The inhibitory activity of
      each against dengue virus (DENV) infection was investigated. Of 33 plants,
      peptides from Acacia catechu extract demonstrated the most pronounced anti-DENV
      activity. Half maximal inhibitory concentration of 0.18 MUg/ml effectively
      inhibited DENV foci formation. Treatment with 1.25 MUg/ml crude peptide extract
      could reduce virus production less than 100-fold with no observable cell
      toxicity. Peptide sequences were determined by high-performance liquid
      chromatography and liquid chromatography-tandem mass spectrometry. Two bioactive
      peptides isolated from Acacia catechu inhibited DENV foci formation >90% at the
      concentration of 50 MUM; therefore, they are recommended for further
      investigation as antiviral peptides against DENV infection.

PMID- 30225998
TI  - Multi-year net ecosystem carbon balance of a restored peatland reveals a return
      to carbon sink.
AB  - Peatlands after drainage and extraction are large sources of carbon (C) to the
      atmosphere. Restoration, through re-wetting and revegetation, aims to return the
      C sink function by re-establishing conditions similar to that of an undrained
      peatland. However, the time needed to re-establish C sequestration is not well
      constrained due to the lack of multi-year measurements. We measured over 3 years
      the net ecosystem exchange of CO2 (NEE), methane ( <mml:math
      xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>F</mml:mi>
      <mml:msub><mml:mi>CH</mml:mi> <mml:mn>4</mml:mn></mml:msub> </mml:msub>
      </mml:math> ), and dissolved organic carbon (DOC) at a restored post-extraction
      peatland (RES) in southeast Canada (restored 14 years prior to the start of the
      study) and compared our observations to the C balance of an intact reference
      peatland (REF) that has a long-term continuous flux record and is in the same
      climate zone. Small but significant differences in winter respiration driven by
      temperature were mainly responsible for differences in cumulative NEE between
      years. Low growing season inter-annual variability was linked to constancy of the
      initial spring water table position, controlled by the blocked drainage ditches
      and the presence of water storage structures (bunds and pools). Half-hour
      <mml:math
      xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>F</mml:mi>
      <mml:msub><mml:mi>CH</mml:mi> <mml:mn>4</mml:mn></mml:msub> </mml:msub>
      </mml:math> at RES was small except when Typha latifolia-invaded drainage ditches
      were in the tower footprint; this effect at the ecosystem level was small as
      ditches represent a minor fraction of RES. The restored peatland was an annual
      sink for CO2 (-90 +/- 18 g C m-2  year-1 ), a source of CH4 (4.4 +/- 0.2 g C m-2 
      year-1 ), and a source of DOC (6.9 +/- 2.2 g C m-2  year-1 ), resulting in mean
      net ecosystem uptake of 78 +/- 17 g C m-2  year-1 . Annual NEE at RES was most
      similar to wetter, more productive years at REF. Integrating structures to
      increase water retention, alongside re-establishing key species, have been
      effective at re-establishing the net C sink rate to that of an intact peatland.

PMID- 30225999
TI  - Predictive value of angiogenic proteins in patients with metastatic melanoma
      treated with bevacizumab monotherapy.
AB  - The incidence of malignant melanoma is rising worldwide and survival for
      metastatic disease is still poor. Recently, new treatment options have become
      available. Still, predictive biomarkers are needed to optimise treatment for this
      patient group. In this study, we investigated the predictive value of 60
      angiogenic factors in patients with metastatic melanoma treated with the anti
      vascular endothelial growth factor A antibody bevacizumab. Thirty-five patients
      were included in a clinical phase II trial and baseline serum samples were
      analysed by multiplex protein array. High-serum concentration of Activin A was
      significantly associated with objective response (OR) to treatment (p = 0.014).
      Candidate proteins that indicated a borderline association with treatment
      response were further investigated by immunohistochemistry. Strong expression of
      Activin A, interleukin-1beta, and urokinase-type plasminogen activator receptor
      in metastases was significantly associated with OR (p = 0.011, p = 0.003, and p =
      0.007, respectively), as well as with markers of activated angiogenesis, such as
      higher number of proliferating vessels and the presence of glomeruloid
      microvascular proliferations. Our findings indicate that these proteins may be
      potential predictive markers for treatment with bevacizumab monotherapy.

PMID- 30226000
TI  - Quantifying the lumbar spine movements of surgeons during surgical lists in a
      teaching hospital.
AB  - BACKGROUND: Low back pain (LBP) is a common occupational musculoskeletal
      complaint among health professionals. No research has quantified lumbar movement
      patterns in the surgical workplace, identifying 'at risk' behaviours with
      objective measures. This project aimed to identify lumbar movement patterns and
      change in LBP of surgeons and surgical trainees during a surgical list. METHODS:
      Surgeons or surgical trainees were recruited in a tertiary metropolitan hospital.
      Low back movements were quantified in real time via a monitoring system. This
      measured three-dimensional movement, velocity, acceleration and orientation to
      gravity during a typical theatre session. Pre- and post-surgery LBP, or low back
      injury measures of functional disability were quantified using the Oswestry
      disability index. Mean (standard deviation) and median (interquartile range) low
      back movement patterns were described. A Wilcoxon signed-rank test determined
      differences in LBP recorded from beginning to end of recording periods. RESULTS:
      Participants (n = 28) recorded data for a mean (standard deviation) of 6.1 (2.2)
      h. On average, 27.7 lumbar flexion events were recorded per monitoring session,
      with flexion movements held for >30 s an average of 5.6 times. Many of the
      flexion events were considered low range (between 20 degrees  and 40 degrees )
      with an average of 19.1 events per session. Orthopaedic trainees recorded the
      highest average of lumbar and sustained lumbar flexions per hour (4.13 times).
      LBP significantly increased over the work day (z = -2.53, P = 0.012). CONCLUSION:
      This study provides a base for the understanding of low back movement patterns
      during surgery. This data may be useful in helping surgeons to identify their
      'high risk' movements and prevent low back symptoms.

PMID- 30226001
TI  - Nickel Oxide/Graphene Composites: Synthesis and Applications.
AB  - Nickel oxide (NiO) has emerged as one of the most promising transition-metal
      oxides (TMOs) for electrochemical capacitors, batteries, catalysis, and
      electrochromic films, owing to its cost-effectiveness, abundance, and well
      defined electrochemical properties. Recent studies have identified that mixing
      NiO with graphene or graphene derivatives results in novel composites with
      synergistic effects and superior electrochemical performance. This review
      summarizes the latest advances in composites of NiO with graphene or graphene
      derivatives. The synthetic strategies, morphologies, and electrochemical
      performance of these composites are introduced, as well as their electrochemical
      applications in supercapacitors, batteries, sensors, catalysis, and so forth.
      Finally, tentative conclusions and assessments regarding the opportunities and
      challenges for the future development of these composites and other TMOs/graphene
      or graphene-derived composites are presented.

PMID- 30226004
TI  - High BMI: A New Determinant of Impaired Rubella Immunity During Pregnancy?

PMID- 30226002
TI  - Adipose Tissue Dysfunction Occurs Independently of Obesity in Adipocyte-Specific
      Oncostatin Receptor Knockout Mice.
AB  - OBJECTIVE: This study examined the phenotypic effects of adipocyte-specific
      oncostatin M receptor (OSMR) loss in chow-fed mice. METHODS: Chow-fed adipocyte
      specific OSMR knockout (FKO) mice and littermate OSMRfl/fl controls were studied.
      Tissue weights, insulin sensitivity, adipokine production, and stromal cell
      immunophenotypes were assessed in epididymal fat (eWAT); serum adipokine
      production was also assessed. In vitro, adipocytes were treated with oncostatin
      M, and adipokine gene expression was assessed. RESULTS: Body weights, fasting
      blood glucose levels, and eWAT weights did not differ between genotypes. However,
      the eWAT of OSMRFKO mice was modestly less responsive to insulin stimulation than
      that of OSMRfl/fl mice. Notably, significant increases in adipokines, including C
      reactive protein, lipocalin 2, intercellular adhesion molecule-1, and insulinlike
      growth factor binding protein 6, were observed in the eWAT of OSMRFKO mice. In
      addition, significant increases in fetuin A and intercellular adhesion molecule-1
      were detected in OSMRFKO serum. Flow cytometry revealed a significant increase in
      leukocyte number and modest, but not statistically significant, increases in B
      cells and T cells in the eWAT of OSMRFKO mice. CONCLUSIONS: The chow-fed OSMRFKO
      mice exhibited adipose tissue dysfunction and increased proinflammatory adipokine
      production. These results suggest that intact adipocyte oncostatin M-OSMR
      signaling is necessary for adipose tissue immune cell homeostasis.

PMID- 30226005
TI  - The War Diet Squad.

PMID- 30226003
TI  - Associations of Maternal Diabetes During Pregnancy with Overweight in Offspring:
      Results from the Prospective TEDDY Study.
AB  - OBJECTIVE: This study aimed to determine the relationship between different forms
      of, and potential pathways between, maternal diabetes and childhood obesity at
      different ages. METHODS: Prospective cohort data from The Environmental
      Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324
      children examined from 0.25 to 6 years of age, were analyzed. Cross-sectional and
      longitudinal analyses taking into account potential confounders and effect
      modifiers such as maternal prepregnancy BMI and birth weight z scores were
      performed. RESULTS: Offspring of mothers with gestational diabetes mellitus (GDM)
      or type 1 diabetes mellitus (T1DM) showed a higher BMI standard deviation score
      and increased risk for overweight and obesity at 5.5 years of age than offspring
      of mothers without diabetes. While these associations could be substantially
      explained by maternal prepregnancy BMI in offspring of mothers with GDM,
      significant associations disappeared after adjustment for birth weight z scores
      in offspring of T1DM mothers. Furthermore, overweight risk became stronger with
      increasing age in offspring of mothers with diabetes compared with offspring of
      mothers without diabetes. CONCLUSIONS: Maternal diabetes is associated with
      increased risk of offspring overweight, and the association appears to get
      stronger as children grow older. Indeed, intrauterine exposure to maternal T1DM
      may predispose children to later obesity through increased birth weight, while
      maternal BMI is more important in children exposed to GDM.

PMID- 30226006
TI  - Pooled Findings from the LIFE-Moms Randomized Trials: Where Do We Go from Here?

PMID- 30226007
TI  - Night Shift Work Before and During Pregnancy and Offspring Weight Outcomes
      Through Adolescence.
AB  - OBJECTIVE: This study aimed to investigate associations between maternal history
      of rotating night shift nursing work before pregnancy and number of night shifts
      worked during pregnancy with offspring weight outcomes from early life through
      adolescence. METHODS: More than 4,000 children, enrolled in the second phase of
      the Growing Up Today Study between 2004 and 2013, and their mothers participating
      in the Nurses' Health Study II were included in our analyses. RESULTS: Children
      of women with and without a history of rotating night shift work before pregnancy
      were similar in birth weight and body size at age 5. However, for mothers with
      night shift work before pregnancy, their children had a modestly elevated risk of
      having overweight or obesity (relative risk = 1.11; 95% CI: 1.02-1.21), which was
      stronger for persistently having overweight or obesity during adolescence and
      early adulthood. Longer duration of rotating night shift work was not associated
      with any of these weight outcomes. Weight outcomes of children of women with
      versus without night shift work during pregnancy were similar, regardless of
      frequency of night shifts worked during pregnancy (all P > 0.09). CONCLUSIONS:
      Overall, nurses' night shift work before or during pregnancy did not affect
      offspring weight outcomes. Future larger studies should explore these
      associations in more detail.

PMID- 30226008
TI  - Maternal High-Fat Diet Effects on Adaptations to Metabolic Challenges in Male and
      Female Juvenile Nonhuman Primates.
AB  - OBJECTIVE: This study aimed to determine whether maternal high-fat diet (HFD)
      consumption in nonhuman primates alters the ability of offspring to adapt
      metabolically to nutrient and caloric challenges. METHODS: Offspring from
      Japanese macaque dams fed either a control (CTR) diet or HFD were weaned onto a
      CTR diet creating two groups: maternal HFD (mHFD, n = 18) and maternal CTR (mCTR)
      diet (n = 12). Male and female offspring were exposed to a 5-day 30% calorie
      restriction and to a 35-day HFD challenge (HFDC), at 16 and 24 months of age,
      respectively. Caloric intake, body weight, and energy expenditure were measured.
      RESULTS: Offspring from both groups showed similar body weight, food intake, and
      metabolic adaptations to a 5-day calorie restriction. mHFD offspring demonstrated
      increased food intake and early weight gain in response to a 35-day HFDC;
      however, group differences in weight dissipated during the challenge. Unlike mCTR
      animals, the mHFD group had a significant increase in fasting insulin after acute
      HFD exposure. CONCLUSIONS: The current findings indicate that offspring exposed
      to an mHFD show metabolic adaptations to calorie restriction that are largely
      similar to those of offspring exposed to a mCTR diet but show delayed adaptation
      upon exposure to an acute HFDC.

PMID- 30226009
TI  - Effects of Self-Conditioning Techniques (Self-Hypnosis) in Promoting Weight Loss
      in Patients with Severe Obesity: A Randomized Controlled Trial.
AB  - OBJECTIVE: The usefulness of the rapid-induction techniques of hypnosis as an
      adjunctive weight-loss treatment has not been defined. This randomized controlled
      trial evaluated whether self-conditioning techniques (self-hypnosis) added to
      lifestyle interventions contributed to weight loss (primary outcome), changes in
      metabolic and inflammatory variables, and quality of life (QoL) improvement
      (secondary outcomes) in severe obesity. METHODS: Individuals (with BMI = 35-50
      kg/m2 ) without organic or psychiatric comorbidity were randomly assigned to the
      intervention (n = 60) or control arm (n = 60). All received exercise and
      behavioral recommendations and individualized diets. The intervention consisted
      of three hypnosis sessions, during which self-hypnosis was taught to increase
      self-control before eating. Diet, exercise, satiety, QoL, anthropometric
      measurements, and blood variables were collected and measured at enrollment and
      at 1 year (trial end). RESULTS: A similar weight loss was observed in the
      intervention (-6.5 kg) and control (-5.6 kg) arms (beta = -0.45; 95% CI: -3.78 to
      2.88; P = 0.79). However, habitual hypnosis users lost more weight (-9.6 kg; beta
      = -10.2; 95% CI: -14.2 to -6.18; P < 0.001) and greatly reduced their caloric
      intake (-682.5 kcal; beta = -643.6; 95% CI: -1064.0 to -223.2; P = 0.005) in
      linear regression models. At trial end, the intervention arm showed lower C
      reactive protein values (beta = -2.55; 95% CI: -3.80 to -1.31; P < 0.001), higher
      satiety (beta = 19.2; 95% CI: 7.71-30.6; P = 0.001), and better QoL (beta = 0.09;
      95% CI: 0.02-0.16; P = 0.01). CONCLUSIONS: Self-hypnosis was not associated with
      differences in weight change but was associated with improved satiety, QoL, and
      inflammation. Indeed, habitual hypnosis users showed a greater weight loss.

PMID- 30226011
TI  - Weight-Related Terms Differentially Affect Self-Efficacy and Perception of
      Obesity.
AB  - OBJECTIVE: Little work has explored the effect of weight-related terms on
      treatment initiation; only one study has investigated weight-related terms and
      the psychological constructs associated with treatment uptake. The present study
      examines the effects of four common weight-related terms on treatment initiation
      and the moderating effect of weight bias internalization. METHODS: Adult
      participants with overweight and obesity (n = 436) were recruited online and
      asked to read three vignettes describing clinical encounters; the weight-related
      term (i.e., "weight," "BMI," "obesity," or "fat") was varied randomly.
      Participants then reported self-efficacy, cognitive and emotional illness beliefs
      about obesity (i.e., illness perception), and interest in a weight loss program.
      RESULTS: The term "obesity" resulted in the greatest self-efficacy and perceived
      control over obesity. "Fat" resulted in the least illness coherence (i.e.,
      understanding of obesity). Weight bias internalization did not moderate the
      effect of term on self-efficacy, nor did it moderate illness perception. No
      differences in weight loss program enrollment were observed. CONCLUSIONS: Use of
      the term "obesity" may promote patients' perceived control and self-efficacy. Use
      of "fat" should be avoided. Results suggest that, despite patient and clinician
      preference for euphemistic weight terms, use of clinical language such as
      "obesity" may perform better in provider intervention.

PMID- 30226010
TI  - Obesity in Adolescence Predicts Lower Educational Attainment and Income in
      Adulthood: The Project EAT Longitudinal Study.
AB  - OBJECTIVE: Prospective associations between obesity in adolescence and adult
      socioeconomic outcomes, and potential mediators, were examined in a contemporary
      cohort. METHODS: Longitudinal data collected in 1998 to 1999 (Project EAT-I) and
      2015 to 2016 (EAT-IV) were analyzed for 1,796 participants who provided data at
      both time points. Adolescents (mean age = 14.8 years) self-reported demographic
      and psychosocial variables (EAT-I) and follow-up outcomes (EAT-IV). Body weight
      and height were directly measured. Bachelor's degree or more education, income >=
      US $50,000, and partnered status at follow-up were examined by baseline obesity
      (>95th BMI percentile) using logistic regression. Self-esteem, depression, and
      weight-related teasing were examined as mediators using multivariate probit
      regressions. All analyses were adjusted for race, baseline age, and parent
      socioeconomic status. RESULTS: Girls with obesity were significantly less likely
      to have achieved a bachelor's degree (OR 0.32, 95% CI [0.18, 0.58]; P < 0.001),
      earn >= $50,000 annually (OR 0.57, 95% CI [0.33, 0.99]; P < 0.04), or be
      partnered (OR 0.45, 95% CI [0.27, 0.75]; P < 0.002) in adulthood. No associations
      were observed among boys. Among girls, depression mediated 8.5% and 23.6% of the
      association between adolescent obesity and adult education and income,
      respectively. CONCLUSIONS: Adolescent girls with obesity have lower educational
      attainment and income and are less likely to be partnered in later adulthood.
      Depression may partly mediate the associations.

PMID- 30226012
TI  - The Mediating Role of Sleep Quality and Quantity in the Link Between Food
      Insecurity and Obesity Across Race and Ethnicity.
AB  - OBJECTIVE: The objective of the study was to examine the mediating role of sleep
      quality and quantity in the relationship between food insecurity and obesity
      across races/ethnicities. METHODS: Bivariate negative binomial regression and
      multinomial logistic regression were used to examine direct associations between
      food insecurity and sleep quality and quantity among non-Hispanic Native Hawaiian
      and other Pacific Islanders (NHPI) relative to non-Hispanic White, Black, Asian,
      and Hispanic individuals with obesity. The potential outcomes approach and
      adjusted Wald test were used to explore the mediating role of sleep quality and
      quantity and the moderating role of race/ethnicity, respectively. RESULTS: Among
      adults with obesity, the study found a positive and direct relationship between
      food insecurity and trouble falling asleep in each racial/ethnic group. Trouble
      staying asleep was associated with food insecurity in each racial/ethnic group,
      except in the Asian group. Positive and direct associations were observed between
      food insecurity and short/very short sleep. A positive and direct relationship
      was found between food insecurity and having obesity in each racial/ethnic group,
      except in the Black group. Sleep quality and sleep quantity partially mediated
      the relationship between food insecurity and obesity in non-Hispanic NHPI, White,
      Asian, and Hispanic individuals. Race/ethnicity moderated the indirect effects of
      food insecurity on sleep quality and quantity. CONCLUSIONS: Food security and
      sleep hygiene should be an integral part of the fight against obesity.

PMID- 30226013
TI  - RADseq data reveal ancient, but not pervasive, introgression between Californian
      tree and scrub oak species (Quercus sect. Quercus: Fagaceae).
AB  - A long-term debate in evolutionary biology is the extent to which reproductive
      isolation is a necessary element of speciation. Hybridizing plants in general are
      cited as evidence against this notion, and oaks specifically have been used as
      the classic example of species maintenance without reproductive isolation. Here,
      we use thousands of SNPs generated by RAD sequencing to describe the phylogeny of
      a set of sympatric white oak species in California and then test whether these
      species exhibit pervasive interspecific gene exchange. Using RAD sequencing, we
      first constructed a phylogeny of ten oak species found in California. Our
      phylogeny revealed that seven scrub oak taxa occur within one clade that diverged
      from a common ancestor with Q. lobata, that they comprise two subclades, and they
      are not monophyletic but include the widespread tree oak Q. douglasii. Next, we
      searched for genomic patterns of allele sharing consistent with gene flow between
      long-divergent tree oaks with scrub oaks. Specifically, we utilized the D
      statistic as well as model-based inference to compare the signature of shared
      alleles between two focal tree species (Q. lobata and Q. engelmannii) with
      multiple scrub species within the two subclades. We found that introgression is
      not equally pervasive between sympatric tree and scrub oak species. Instead, gene
      flow commonly occurs from scrub oaks to recently sympatric Q. engelmannii, but
      less so from scrub oaks to long-sympatric Q. lobata. This case study illustrates
      the influence of ancient introgression and impact of reproductive isolating
      mechanisms in preventing indiscriminate interspecific gene exchange.

PMID- 30226014
TI  - Peripheral blood toll-like receptor 4 correlates response to candida
      immunotherapy of warts.
AB  - Human papilloma virus infection may be self-limiting; however, some cases may
      spread. There are no factors predicting the prognosis of such infections. The
      present study aimed to evaluate the significance of TLR4 expression in predicting
      the response of warts to candida immunotherapy. A total of 60 patients with
      different types of warts were included in the present study. A total volume of 2
      ml venous blood was collected and real-time polymerase chain reaction was used to
      determine expression of TLR4. Patients were subjected to intralesional injection
      of Candida antigen into the largest wart at 2-week intervals until complete
      clearance or for a maximum of six sessions. Of the total 58 patients available
      for analysis of study results, 44 patients (75.9%) showed complete resolution
      with better response in younger ages. The TLR4 expression in patients with
      complete and partial response was significantly higher than that in patients who
      had no response (p = .006). Among our patients, 48.3% showed no side effects,
      44.8% showed local reactions, and 6.9% showed systemic side effects. Only four
      patients showed recurrence after 6 months. Using receiver operating
      characteristic curve analysis, at cutoff of expression level >12 is accompanied
      by 100% specificity of TLR4 in predicting treatment response to candida
      immunotherapy. Candida immunotherapy is an effective warts treatment, especially
      in young patients. Higher PMBC TLR4 levels can predict response to candida
      immunotherapy.

PMID- 30226015
TI  - Scarce case of giant coronary artery aneurysm combined with huge pseudoaneurysm
      causing cardiac tamponade.

PMID- 30226016
TI  - High prevalence of comorbid autoimmune diseases in adults with type 1 diabetes
      from the HealthFacts database.
AB  - BACKGROUND: Patients with type 1 diabetes (T1D) are at risk for other autoimmune
      diseases (ie, polyautoimmunity). The prevalence and risk factors of this
      phenomenon have been underreported in adults and ethnic minorities, and data are
      lacking regarding non-endocrine autoimmune diseases. METHODS: Study population
      data were gathered from HealthFacts, a deidentified patient database compiled
      from electronic medical records systems in the US. Patients with an International
      Classification of Diseases diagnosis code specifying T1D were included in the
      study, whereas those with a diagnosis of type 2 diabetes were excluded. RESULTS:
      The cross-sectional study cohort comprised 158 865 adults with T1D (mean [+/-SD]
      age 51.4 +/- 18.9 years, 52.5% female). The most common autoimmune diseases were
      thyroid disease (20.1%), systemic rheumatic diseases (3.4%), rheumatoid arthritis
      specifically (2.0%), and gastrointestinal autoimmune diseases (1.4%). Most of the
      autoimmune diseases were more common in women (eg hypothyroidism,
      hyperthyroidism, celiac disease, rheumatoid arthritis, lupus, and Sjogren
      syndrome). Caucasians were more likely than other ethnicities to have an
      additional autoimmune disease. The prevalence of autoimmune diseases increased
      with increasing age, significantly in women, such that 38.5% of women over 80
      years of age had an additional autoimmune disease, compared with 17.9% of women
      aged <=29 years. CONCLUSIONS: Additional autoimmunity represents a significant
      comorbidity in patients with T1D. Autoimmune diseases are more common in
      Caucasians and in women, and increase with age. Clinicians treating patients with
      T1D should be aware of the risk factors for additional autoimmune diseases.

PMID- 30226017
TI  - Detection of an HLA-B*58 variant, HLA-B*58:19, by sequence-based typing in a
      Taiwanese individual.
AB  - One nucleotide substitution at codon 152 of HLA-B*58:01:01:01 results in a novel
      allele, HLA-B*58:19.

PMID- 30226019
TI  - Acute-on-chronic liver failure exists in patients with hepatitis B virus-related
      decompensated cirrhosis.
AB  - OBJECTIVE: This research sought to verify whether acute-on-chronic liver failure
      (ACLF) develops in hepatitis B virus (HBV)-related cirrhotic patients with
      previous decompensation and to identify the similarity between assumed ACLF
      patients and those with ACLF that developed from compensated cirrhosis. METHODS:
      Patients with HBV-related cirrhosis were retrospectively screened and divided
      into the cirrhotic patients with first acute decompensation (AD) group and those
      with previous decompensation. Patients' characteristics, changes in laboratory
      results during hospitalization such as serum levels of total bilirubin (TB),
      creatinine (Cr) and white blood cell (WBC) counts, the Model for End-Stage Liver
      Disease (MELD) score and the 28-day and 1-year mortality rates were compared.
      RESULTS: Altogether 890 patients were enrolled and divided into the compensated
      cirrhotic group with first AD (n = 400; 157 of whom diagnosed as ACLF within 28
      days after admission according to the European Association for the Study of the
      Liver-Chronic Liver Failure [EASL-CLIF] criteria) and those with previous
      decompensation (n = 490; of whom 143 met the ACLF criteria [assumed ACLF]). There
      was no significant difference in 28-day mortality between the assumed ACLF group
      with previous decompensation and ACLF group with first AD. The WBC count, TB and
      Cr levels, international normalized ratio and MELD score exhibited similar
      variations in both groups at days 1, 7 and 28; however, these values in both ACLF
      groups significantly differed from the non-ACLF group. CONCLUSION: HBV-related
      cirrhotic patients with previous decompensation who met the ACLF criteria had
      similar characteristic to ACLF patients with first AD.

PMID- 30226020
TI  - Two novel HLA-B alleles, HLA-B*53:01:17 and -B*58:83, found in patients from
      Guinea-Bissau.
AB  - Novel HLA-B alleles HLA-B*53:01:17 and HLA-B*58:83 are described in two patients
      from Guinea-Bissau.

PMID- 30226021
TI  - Response to "Interaction of Dasabuvir With Clopidogrel: Did Predictions by
      Physiologically Based Pharmacokinetics Modeling Pass the Test?"

PMID- 30226022
TI  - "Boom, Headshot!": Violent first-person shooter (FPS) video games that reward
      headshots train individuals to aim for the head when shooting a realistic
      firearm.
AB  - When shooting a gun at a human target, firearms training instructors teach
      individuals to shoot for the upper torso because it is the largest lethal target
      on the human body. In contrast, violent first-person shooter (FPS) video games
      reward players for headshots. The head is the smallest lethal target, and
      requires careful aim to hit. In this experiment, participants were randomly
      assigned to play a violent FPS game with humanoid targets that rewarded
      headshots, a nonviolent shooting game that punished hits to bull's-eye targets
      with faces, or a nonviolent non-shooting game. After gameplay, participants shot
      16 "bullets" from a realistic gun at a life-sized human-shaped mannequin.
      Participants were told to hit the mannequin with as many bullets as possible, but
      they were not told where to aim. Consistent with operant conditioning theory,
      participants who played a violent FPS game that rewarded headshots had the most
      hits to the mannequin's head. Participants whose favorite video games were
      violent shooting games also had the most hits to the mannequin's head. These
      findings suggest that FPS games that reward headshots can influence people to aim
      for the head with a realistic gun after the game is turned off, even though the
      head is a much smaller target to hit and they are much less likely to hit another
      body part if they miss. FPS games are often used to train soldiers and police
      officers, but these findings suggest that such games might train individuals to
      hit the wrong part of the body.

PMID- 30226023
TI  - Gastric emptying in children with type 1 diabetes mellitus: A pilot study.
AB  - AIM: Delayed gastric emptying (GE) has been demonstrated in adults with type 1
      diabetes mellitus (T1DM). Little is known about GE in children with T1DM. Most
      methods to measure GE are invasive, that is, scintigraphy, or are only indirectly
      related to GE, that is, electrogastrography. Carbon-13 breath testing is a non
      invasive, very low-risk procedure that accurately correlates with GE time. This
      was a pilot study to determine the feasibility of using carbon-13 breath testing
      to measure GE in children with T1DM and healthy controls. METHODS: Cases were
      recruited from children aged 7-15 years presenting to the paediatric diabetic
      clinic at Christchurch Hospital. Controls were peers of the cases. Children with
      known gastrointestinal disease were excluded. After an overnight fast, each child
      ate a standardised pancake labelled with carbon-13 sodium octanoate. Samples of
      breath were collected over a 4-h period. Samples were analysed by mass
      spectrometry. GE half time (GET1/2 ) and GE coefficients (GEC) were calculated by
      linear regression to obtain a measure of GE. RESULTS: A total of 19 cases and 15
      age- and gender-matched controls underwent testing. The mean GEC in the cases was
      3.19 (+/-0.38) and 2.90 (+/-0.29) in controls (P = 0.03), with an effect size =
      0.86. Mean GET1/2 in the cases was 99 (52.1) min and 103 (27.5) in controls (P =
      0.8), with an effect size = 0.1. CONCLUSION: The study generated results
      suggesting that a larger study will be worthwhile to investigate the relationship
      between GE and T1DM.

PMID- 30226024
TI  - ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and
      classification of diabetes in children and adolescents.

PMID- 30226025
TI  - Histological findings correlated with clinical outcomes in telangiectasia treated
      with ohmic thermolysis and 940 nm laser.
AB  - BACKGROUND: Heat modalities are commonly used as either primary or adjunctive
      treatment for telangiectasia. Minimal information is available as to the nature
      of injury to the vessel and surrounding tissue. METHOD: A total of 135 patients
      were treated over a 2-year period using ohmic thermolysis (45), 940 nm laser
      (50), and 940 nm laser with sclerotherapy (40). After treatment, 1 mm biopsies
      were done in selected patients in each group. Clinical correlation was studied in
      each group by observing vessel response at 4-6 weeks postprocedure. RESULTS:
      Ohmic thermolysis produces electrodessication of the squamous epithelium,
      reticular dermis, and fusion of the target vessel. 940 nm laser results include
      squamous epithelial damage, subcutaneous water blister, collagen denaturation,
      and vessel endothelial cell loss with thrombus at point of maximal impact. The
      addition of sclerotherapy at time of laser potentiates vessel damage. There was
      no long-term skin sequelae after treatment when each device is used at
      recommended settings and on appropriate vessel size. CONCLUSION: Each device
      causes damage to the squamous epithelium and papillary reticular dermis that is
      transient. Ohmic thermolysis provides vessel clearance of >90% in telangiectasias
      <0.5 mm. 940 nm laser effectiveness is <70% for vessel clearance, but improves to
      >90% when sclerotherapy is performed at time of treatment.

PMID- 30226027
TI  - Molecular and functional insights into gonadotropin hormone receptor dimerization
      and oligomerization.
AB  - The gonadotropin hormones, follicle stimulating hormone and luteinizing hormone,
      are essential for reproduction. They work in concert to control multiple aspects
      of gonadal function to ultimately produce meiotically competent and fertilizable
      gametes, provide the optimal endometrial environment and support for implantation
      and maintain pregnancy via progesterone production throughout the first trimester
      of pregnancy. These complex and multidimensional functions are mediated via the
      gonadotropin hormone receptors, luteinizing hormone receptor and follicle
      stimulating hormone receptor, Class A G protein-coupled receptors (GPCR), which
      couple to multiple G protein-dependent and independent signal pathways to control
      these physiological processes. Over the last two decades, a plethora of
      experimental evidence has shown that GPCRs can associate to form dimers and
      oligomers. This association provides a means of mediating the diverse functional
      requirements of a single receptor subtype and for the gonadotropin hormone
      receptors, has been shown to alter the pharmacology and signal activation profile
      of these receptors. This review will detail the historical and current evidence
      detailing the formation of gonadotropin hormone receptor homomers and heteromers.
      We will discuss the functional insights gained from in vitro and in vivo studies,
      and the potential impact in modulating reproductive health and disease.

PMID- 30226028
TI  - New insights into maternity care design and delivery: editorial commentary.

PMID- 30226026
TI  - New mitochondrial primers for metabarcoding of insects, designed and evaluated
      using in silico methods.
AB  - Insect metabarcoding has been mainly based on PCR amplification of short
      fragments within the "barcoding region" of the gene cytochrome oxidase I (COI).
      However, because of the variability of this gene, it has been difficult to design
      good universal PCR primers. Most primers used today are associated with gaps in
      the taxonomic coverage or amplification biases that make the results less
      reliable and impede the detection of species that are present in the sample. We
      identify new primers for insect metabarcoding using computational approaches
      (ecoprimers and degeprime) applied to the most comprehensive reference databases
      of mitochondrial genomes of Hexapoda assembled to date. New primers are evaluated
      in silico against previously published primers in terms of taxonomic coverage and
      resolution of the corresponding amplicons. For the latter criterion, we propose a
      new index, exclusive taxonomic resolution, which is a more biologically
      meaningful measure than the standard index used today. Our results show that the
      best markers are found in the ribosomal RNA genes (12S and 16S); they resolve
      about 90% of the genetically distinct species in the reference database. Some
      markers in protein-coding genes provide similar performance but only at much
      higher levels of primer degeneracy. Combining two of the best individual markers
      improves the effective taxonomic resolution with up to 10%. The resolution is
      strongly dependent on insect taxon: COI primers detect 40% of Hymenoptera, while
      12S primers detect 12% of Collembola. Our results indicate that amplicon-based
      metabarcoding of insect samples can be improved by choosing other primers than
      those commonly used today.

PMID- 30226029
TI  - Deferred stenting for acute myocardial infarction of late admission.

PMID- 30226030
TI  - A novel approach to quantification of aortic valve calcifications in patients
      undergoing transcatheter aortic valve implantation.
AB  - BACKGROUND: Precise calcium evaluation in the aortic complex may be complicated.
      We aimed to assess the usefulness of a novel semi-automatic algorithm for multi
      slice computed tomography-derived (MSCT) quantitative estimation of aortic valve
      calcifications (AVC) in patients with severe aortic stenosis (AS) undergoing
      transcatheter aortic valve implantation (TAVI). METHODS: Ten patients with severe
      AS who underwent TAVI with Edwards Sapien S3 26 mm prosthesis and had a pre
      procedural MSCT scan were included. Data on baseline characteristics, procedural
      and long-term outcomes were collected prospectively. Pre-procedural MSCT data was
      used for AVC evaluation with 3D modeling (calcium volume, thickness, area,
      density, and distribution) in a dedicated program. RESULTS: Mean calcium
      thickness was 4.6 (3.6-5.8) mm. Median calcium are was 333.6 (274.7- 386.7) mm2.
      We found a significant correlation between larger maximal calcium layer thickness
      and PVL occurrence after TAVI (p=0.039). The radial representation of the calcium
      distribution allowed to divide aortic valve into 3 zones and to compare each zone
      to parallel zone on TTE images. In zones with PVL >=2 mean AVC was higher than in
      zones with PVL <2 (7354.6+/-4020.4 pixels vs. 4325.1+/-1790.6 pixels; p=0.018).
      Based on ROC analysis, the optimal cut-off value of AVC to predict PVL >=2 was
      >6506 pixels with 57.1% sensitivity and 90.5% specificity (AUC 0.762 (95%CI 0.564
      to 0.901), p=0.029). CONCLUSIONS: Multiplane AVC quantitative evaluation provided
      details on total calcium amount, pattern and distribution in aortic valve.
      Established AVC parameters allowed better visualization of an operating area and
      prediction of PVL after TAVI.

PMID- 30226031
TI  - Degeneration of prosthesis after transcatheter aortic valve implantation.
AB  - With the expanding indication of transcatheter aortic valve implantation (TAVI)
      to younger, lower risk population, transcatheter aortic valve (TAV) long-term
      durability is becoming an emerging issue to face with. Recently, the
      standardization of structural valve deterioration (SVD) definition by a join
      committee of the European Association of Percutaneous Cardiovascular
      Interventions (EAPCI), the European Society of Cardiology (ESC) and the European
      Association for Cardio-Thoracic Surgery (EACTS) has permitted to evaluate for the
      first time the rates of TAV durability with comparable endpoint. A few studies
      reporting on structural valve dysfunction (SVD) after TAVI up to 8 years using
      this standardized criteria have found very low rates of valve deterioration, thus
      supporting the adoption of TAVI treatment even for younger patients. For patients
      showing SVD at follow-ups, the VIVID (Valve-in-Valve International Data) group
      recently proposed an algorithm for their management. Re-do TAVI seems to be a
      safer and valid alternative to re-do surgery for symptomatic patients. This
      article review will go through the current evidence of TAV durability, describing
      the types of failure and strategies of treatment.

PMID- 30226032
TI  - Interaction study between antiplatelet agents, anticoagulants, diabetic therapy
      and a novel delivery form of quercetin.
AB  - BACKGROUND: In this pilot non-interference clinical study we evaluated possible
      interactions between Quercetin Phytosome(r), an innovative delivery form of
      quercetin, and antiplatelet agents, anticoagulants, and anti-diabetic therapy in
      otherwise healthy subjects. METHODS: Interaction with antiplatelet therapy was
      assessed through the bleeding time (BT) test in 30 patients treated with
      acetylsalicylic acid, ticlopidine or clopidogrel before and after 10 days of
      supplementation with Quercetin Phytosome(r). Interaction with anticoagulants, was
      evaluated by measuring the International Normalized Ratio (INR) in 20 patients
      using warfarin or dabigatran before and after 20 days of supplementation with
      Quercetin Phytosome(r). Lastly, glycaemia and glycated hemoglobin were measured
      in 12 diabetic patients treated with metformin and restricted diet before and
      after 20 days of supplementation with Quercetin Phytosome(r). RESULTS: After 10
      days of supplementation no significant difference was observed in mean BT in
      patients treated with acetylsalicylic acid, ticlopidine or clopidogrel at
      standard dosages. Similarly, after 20 days of supplementation, the INR level
      among patients assuming warfarin or dabigatran was not statistically different
      from baseline. Lastly, no statistically significant difference in mean levels of
      glycaemia and glycated haemoglobin was reported before and after 20 days of
      complementary administration of Quercetin Phytosome(r) in diabetic patients
      treated with metformin and restricted diet. CONCLUSIONS: Quercetin Phytosome(r)
      does not alter the antiplatelet activity of the most common antiplatelet agents,
      has no impact on the INR values in stable patients treated with warfarin or
      dabigatran, and does not influence the metabolic control of diabetic patient
      treated with metformin.

PMID- 30226033
TI  - Prospective registry on cerebral oximetry-guided transcarotid TAVI in patients
      with moderate-high risk aortic stenosis.
AB  - AIM OF STUDY: The aim of the study was to assess safety TAVI procedure through
      the common carotid artery in high-vascular-risk patients. METHODS: The approach
      was selected by a multidisciplinary (cardiologists and cardiac surgeons) heart
      team after analyzing preoperative coronary angiography, TTE and MSCT of the
      peripheral arteries. Patients with the following conditions were qualified to the
      transcarotid access: severe PAD (stenotic, heavily calcified), tortuous or small
      diameter < 6 mm iliofemoral arteries, descending and abdominal aortic disease.
      RESULTS: Ten TC TAVI procedures were performed in our hospital from September
      2017 to May 2018. There were no in-hospital deaths or strokes. The procedural
      success rate defined as the implantation of the valve with no coronary
      obstruction and less than moderate paravalvular leak was 100%. Parameters of
      regional cerebral oximetry were symmetrical on the left and right side in all
      cases and only during rapid ventricular pacing transiently decreased below the
      value of 50%. Postoperative cerebrovascular complications and myocardial
      infarctions were not observed. Statistically significant reduction of the
      echocardiographic parameters (PGmax and PGmean, Vmax) were observed. Mild
      paravalvular leaks occurred in 4 patients. Additionally, the heart failure
      symptoms diminished after the procedure from a median class III to class II. In
      the 3-month follow-up, mortality is 10% (unknown cause of death of one patient).
      The mean NYHA class of the other patients is II. Echocardiographic parameters are
      comparable to postoperative day 4. CONCLUSIONS: The pilot registry showed the
      safety of transcarotid approach in patients with the anatomy precluding the
      transfemoral approach.

PMID- 30226034
TI  - Thinking outside the box; off-label use of the Bispectral Index (BIS) within
      context and limitations for conditions other than depth of anesthesia. Light and
      shadow of the BIS.
AB  - Numerous articles appeared in literature using Brain Function Monitors (BFM) such
      as the bispectral index (BIS) to assess cerebral cognitive conditions not related
      to depth of anesthesia. The BIS cannot be considered a "true" reflection of the
      electroencephalography (EEG) signal nor an independent measure of brain function.
      The BIS algorithm was retrospectively derived from EEG changes with incremental
      doses of gamma-amino butyric acid (GABA)ergic anesthetic agents while measuring 3
      descriptors. In many instances we are confronted with BIS values that do not
      concur with clinically judged anesthetic state arising from an underlying
      alteration of the patients' own EEG. Because the BIS is an EEG derived parameter;
      conditions that can "alter" the raw EEG signal would subsequently change the BIS
      to reflect other unrelated EEG events of patient-dependent pathophysiologic
      perturbations. Could we use the BIS monitor outside the scope of the operating
      room to "grade" other EEG conditions? Actually the answer to that seems to be a
      "very cautious" yes. Because the BIS is a rather appealing scale from 100 to 0,
      it is tempting to find numerical cut-off values for conditions that are already
      clinically graded like West Haven hepatic encephalopathy. Having said that I
      strongly argue against going as far as using BIS in critical care unit (CCU)
      setting, there are too much heterogeneity and many disease states in the CCU
      patients, other than sedatives /hypnotics, that would strongly influence BIS
      values, in effect rendering the BIS not only useless most of the time but can
      also be misleading.

PMID- 30226035
TI  - Incidence of difficult airway in thoracic anesthesia practice.

PMID- 30226036
TI  - The challenge of advance care planning: the new Italian law.

PMID- 30226037
TI  - Myocardial injury after non cardiac surgery: troponin assay is not enough... We
      need perioperative bearings.

PMID- 30226038
TI  - Combining Linker Design and Linker-Exchange Strategies for the Synthesis of a
      Stable Large-Pore Zr-Based Metal-Organic Framework.
AB  - A Zr(IV)-based metal-organic framework (MOF), termed reo-MOF-1
      [Zr6O8(H2O)8(SNDC)4], composed of 4-sulfonaphthalene-2,6-dicarboxylate (HSNDC2-)
      linkers and Zr6O8(H2O)8(CO2)8 clusters was synthesized by solvothermal synthesis.
      Structural analysis revealed that reo-MOF-1 adopts the reo topology highlighted
      with large cuboctahedral cages (23 A). This structure is similar to that found in
      DUT-52 (fcu topology), however, reo-MOF-1 lacks the body-centered packing of the
      12-connected Zr6O4(OH)4(CO2)12 clusters, which is attributed to the subtle, but
      crucial influence in the bulkiness of functional groups on the linkers. The
      control experiments, where the ratio of H3SNDC/naphthalene-2,6-dicarboxylate
      linkers was varied, also support our finding that the bulky functionalities play
      a key role for defect-controlled synthesis. The reo-MOF-1A framework was obtained
      by linker exchange to yield a chemically and thermally stable material despite
      its large pores. Remarkably, reo-MOF-1A exhibits permanent porosity (Brunauer
      Emmett-Teller and Langmuir surface areas of 2104 and 2203 m2 g-1, respectively).
      Owing to these remarkable structural features, reo-MOF-1A significantly enhances
      the yield in Bronsted acid-catalyzed reactions.

PMID- 30226039
TI  - CeO x-Decorated NiFe-Layered Double Hydroxide for Efficient Alkaline Hydrogen
      Evolution by Oxygen Vacancy Engineering.
AB  - As a promising bifunctional electrocatalyst for water splitting, NiFe-layered
      double hydroxide (NiFe LDH) demonstrates an excellent activity toward oxygen
      evolution reaction (OER) in alkaline solution. However, its hydrogen evolution
      reaction (HER) activity is challenged owing to the poor electronic conductivity
      and insufficient electrochemical active sites. Therefore, a three-dimensional
      self-supporting metal hydroxide/oxide electrode with abundant oxygen vacancies is
      prepared by electrodepositing CeO x nanoparticles on NiFe LDH nanosheets.
      According to the density functional theory calculations and experimental studies,
      the oxygen vacancies at the NiFe LDH/CeO x interface can be introduced
      successfully because of the positive charges accumulation resulting from the
      local electron potential difference between NiFe LDH and CeO x. The oxygen
      vacancies accelerate the electron/ion migration rates, facilitate the charge
      transfer, and increase the electrochemical active sites, which give rise to an
      efficient activity toward HER in alkaline solution. Furthermore, NF@NiFe LDH/CeO
      x needs a lower potential of 1.51 V to drive a current density of 10 mA cm-2 in
      overall water splitting and demonstrates a superior performance compared with the
      benchmark Pt/C and RuO2, which is indicated to be a promising bifunctional
      electrode catalyst.

PMID- 30226040
TI  - Recyclable Amphiphilic Metal Nanoparticle Colloid Enabled Atmospheric Oxidation
      of Alcohols.
AB  - Developing amphiphilic colloid catalysts is essentially important for realizing
      environmentally benign biphasic catalysis under atmospheric conditions. Herein, a
      linear structured plant polyphenol was employed as an amphiphilic stabilizer for
      preparing a series of amphiphilic Pd nanoparticles (PdNPs) colloids. For the as
      prepared PdNPs colloids, the phenolic hydroxyls of plant polyphenols were
      responsible for the stabilization of PdNPs, whereas the rigid aromatic scaffold
      of plant polyphenols effectively suppressed the PdNPs from aggregation by
      providing a high steric effect. Thanks to the coexistence of hydrophilic phenolic
      hydroxyls and hydrophobic aromatic rings, the plant polyphenols induced tunable
      amphiphilic properties into the PdNPs, allowing an easier wetting of PdNPs with
      the substrate molecules. By tuning the content of plant polyphenols in the
      colloid, the particle size (3.17-4.73 nm) and the dispersity of the PdNPs were
      facilely controlled. When applied for atmospheric oxidation of insoluble alcohols
      in water by air, the amphiphilic PdNPs preferentially absorbed the alcohol
      substrates to create a relatively high-substrate-concentration microenvironment,
      which improved the mass transfer in the biphasic catalysis, allowing the
      proceeding of low-temperature (50  degrees C) atmospheric oxidation of diverse
      alcohols with high catalytic conversion, including aliphatic alcohols, cyclic
      aliphatic alcohols, and aromatic alcohols. Furthermore, the amphiphilic PdNPs
      colloid also exhibited excellent reusability with a conversion yield high up to
      97.96% in the fifth cycle. In contrast, the control catalysts of
      poly(vinylpyrrolidone)- and poly(ethylene glycol)-stabilized PdNPs were
      completely inactivated in the fifth cycle. As a consequence, our findings
      provided a new route for developing an environmentally benign aqueous colloid
      catalyst that is both highly active and recyclable for mild biphasic oxidation
      reaction systems.

PMID- 30226041
TI  - Lipid Conversion by Cell-Free Synthesized Phospholipid Methyltransferase Opi3 in
      Defined Nanodisc Membranes Supports an in Trans Mechanism.
AB  - Biomembranes composed of lipids and proteins play central roles in physiological
      processes, and the precise balance between different lipid species is crucial for
      maintaining membrane function. One pathway for the biosynthesis of the abundant
      lipid phosphatidylcholine in eukaryotes involves a membrane-integrated
      phospholipid methyltransferase named Opi3 in yeast. A still unanswered question
      is whether Opi3 can catalyze phosphatidylcholine synthesis in trans, at membrane
      contact sites. While evidence for this activity was obtained from studies with
      complex in vitro-reconstituted systems based on endoplasmic reticulum membranes,
      isolated and purified Opi3 could not be analyzed. We present new insights into
      Opi3 activity by characterizing the in vitro-synthesized enzyme in defined
      hydrophobic environments. Saccharomyces cerevisiae Opi3 was cell-free synthesized
      and either solubilized in detergent micelles or co-translationally inserted into
      preformed nanodisc membranes of different lipid compositions. While detergent
      solubilized Opi3 was inactive, the enzyme inserted into nanodisc membranes showed
      activity and stayed monomeric as revealed by native mass spectrometry. The
      methylation of its lipid substrate dioleoylphosphatidylmonomethylethanolamine to
      phosphatidylcholine was monitored by one-dimensional 31P nuclear magnetic
      resonance. Phosphatidylcholine formation was observed not only in nanodiscs
      containing inserted Opi3 but also in nanodiscs devoid of the enzyme containing
      the lipid substrate. This result gives a clear indication for in trans catalysis
      by Opi3; i.e., it acts on the substrate in juxtaposed membranes, while in cis
      lipid conversion may also contribute. Our established system for the
      characterization of pure Opi3 in defined lipid environments may be applicable to
      other lipid biosynthetic enzymes and help in understanding the subcellular
      organization of lipid synthesis.

PMID- 30226042
TI  - High-Performance Nanowire Hydrogen Sensors by Exploiting the Synergistic Effect
      of Pd Nanoparticles and Metal-Organic Framework Membranes.
AB  - Herein, we report the fabrication of hydrogen gas sensors with enhanced
      sensitivity and excellent selectivity. The sensor device is based on the
      strategic combination of ZnO nanowires (NWs) decorated with palladium
      nanoparticles (Pd NPs) and a molecular sieve metal-organic framework (MOF)
      nanomembrane (ZIF-8). The Pd NPs permit the sensors to reach maximal signal
      responses, whereas the ZIF-8 overcoat enables for an excellent selectivity. Three
      steps were employed for the fabrication: (i) coating of a miniaturized sensor
      with vapor-grown ZnO NWs, (ii) decoration of these NWs with Pd NPs by atomic
      layer deposition, and (iii) partial solvothermal conversion of the tuned NWs
      surface to ZIF-8 nanomembrane. The microstructure and composition investigations
      of the ZIF-8/Pd/ZnO nanostructured materials confirmed the presence of both
      metallic Pd NPs and uniform ZIF-8 thin membrane layer. The integration of these
      nanomaterials within a miniaturized sensor device enabled the assessment of their
      performance for H2 detection at concentrations as low as 10 ppm in the presence
      of various gases such as C6H6, C7H8, C2H5OH, and CH3COCH3. Remarkably high
      response signals of 3.2, 4.7, and 6.7 ( Ra/ Rg) have been measured for H2
      detection at only 10, 30, and 50 ppm, whereas no noticeable response toward other
      tested gases was detected, thus confirming the excellent H2 selectivity obtained
      with such a sensor design. The results obtained showed that the performance of
      gas sensors toward H2 gas can be greatly increased by both the addition of Pd NPs
      and the use of ZIF-8 coating, acting as a molecular sieve membrane. Furthermore,
      the presented strategy could be extended toward the sensing of other species by a
      judicious choice of both the metallic NPs and MOF materials with tuned properties
      for specific molecule detection, thus opening a new avenue for the preparation of
      highly selective sensing devices.

PMID- 30226043
TI  - Electrosynthesis of Well-Defined Metal-Organic Framework Films and the Carbon
      Nanotube Network Derived from Them toward Electrocatalytic Applications.
AB  - An efficient and controllable method to synthesize continuous metal-organic
      framework (MOF) films is highly desired. Herein, we demonstrate a facile and
      universal electrochemical method to synthesize homogeneous and uniform zeolitic
      imidazolate framework (ZIF, a typical class of MOF family) films on various
      macroconductive substrates (e.g., conductive glass, Ni foam and carbon cloth) as
      well as nanostructured substrates (one-dimensional nanorod array, two-dimensional
      nanowall array, and three-dimensional nanoframework). Particularly, the MOF film
      can be easily transformed into hierarchical ordered carbon nanotube networks,
      which display multifunctional electrocatalytic performances, such as excellent
      activity and good long-term stability in overall water splitting and oxygen
      reduction. It is worth mentioning that this is the first reported work for
      electrosynthesis of ZIF films on various conductive substrates, illustrating the
      great potential of the fast and economical method for constructing functional and
      integrated films or electrodes toward energy-related applications.

PMID- 30226044
TI  - Achieving Huge Thermal Conductance of Metallic Nitride on Graphene Through
      Enhanced Elastic and Inelastic Phonon Transmission.
AB  - Low thermal conductance of metal contacts is one of the main challenges in the
      thermal management of nanoscale devices of graphene and other two-dimensional
      (2D) materials. Previous attempts to search for metal contacts with high thermal
      conductance yielded limited success because of the incomplete understanding of
      the origins of low thermal conductance. In this paper, we carefully study the
      intrinsic thermal conductance of metal/graphene/metal interfaces to identify the
      heat transport mechanisms across graphene interfaces. We find that unlike
      metal/diamond interfaces, the intrinsic thermal conductance of most graphene
      interfaces (except Ti and TiN x) is only ~50% of the phonon radiation limit,
      suggesting that heat is carried across graphene interfaces mainly through the
      elastic transmission of phonons. We thus propose a convenient approach to
      substantially enhance the phononic heat transport across metal contacts on
      graphene, by better matching the energy of phonons in metals and graphene, for
      example, using metallic nitrides. We test the idea with TiN x with phonon
      frequencies of up to 1.2 * 1014 rad/s, 39% of the highest phonon frequencies in
      graphene of 3.1 * 1014 rad/s. Interestingly, we obtain a huge thermal conductance
      of 270 MW m-2 K-1 for the TiN x/graphene interface, which is ~140% of the phonon
      radiation limit. Thus, the huge thermal conductance cannot be fully explained by
      enhanced elastic phonon transport alone, but may be partially attributed to
      inelastic phonon transport across the TiN x/graphene interface. Our work provides
      guidance for the search for good metal contacts on 2D materials and devices.

PMID- 30226045
TI  - Standing Enokitake-like Nanowire Films for Highly Stretchable Elastronics.
AB  - Stretchable electronics may enable electronic components to be part of our organs
      ideal for future wearable/implantable biodiagnostic systems. One of key
      challenges is failure of the soft/rigid material interface due to mismatching
      Young's moduli, which limits stretchability and durability of current systems.
      Here, we show that standing enokitake-like gold-nanowire-based films chemically
      bonded to an elastomer can be stretched up to 900% and are highly durable, with
      >93% conductivity recovery even after 2000 stretching/releasing cycles to 800%
      strain. Both experimental and modeling reveal that this superior elastic property
      originates from standing enokitake-like nanowire film structures. The closely
      packed nanoparticle layer sticks to the top of the nanowires, which easily cracks
      under strain, whereas the bottom part of the nanowires is compliant with
      substrate deformation. This leads to tiny V-shaped cracks with a maintained
      electron transport pathway rather than large U-shaped cracks that are frequently
      observed for conventional metal films. We further show that our standing nanowire
      films can serve as current collectors in supercapacitors and second skin-like
      smart masks for facial expression detection.

PMID- 30226046
TI  - One-Step Synthesis of Nonspherical Organosilica Particles with Tunable
      Morphology.
AB  - A one-step sol-gel method was developed to synthesize nonspherical organosilica
      particles with tunable morphology. The morphology of organosilica particles can
      be tuned from spherical to golf ball-like or bowl-like through varying the molar
      ratio of tetraethoxysilane (TEOS) to vinyltrimethoxysilane (VTMS) in the
      precursors. The morphology and interior structure of the organosilica particles
      were observed by scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM), respectively. The effect of ammonia concentration on the
      morphology of organosilica particles was investigated. The growth process of golf
      ball-like and bowl-like particles was tracked by SEM in detail, and the formation
      mechanism of nonspherical organosilica particles was also proposed.

PMID- 30226047
TI  - Evaluating the Cell Membrane Penetration Potential of Lipid-Soluble Compounds
      Using Supported Phospholipid Bilayers.
AB  - Supported phospholipid bilayers (SPBs) are promising models for studying the
      passive penetration of lipid-soluble compounds into cells and cell membranes. A
      widely used tool to characterize molecular SPB interactions is the quartz crystal
      microbalance with dissipation monitoring (QCM-D). As QCM-D provides access to the
      mass density of supported membranes, it is well-suited to examine surface
      adsorption and membrane disruption phenomena. In the present study, we report on
      a novel approach to characterize SPB interactions with low molecular weight lipid
      soluble substances. SPBs were formed on a silica-coated QCM-D crystal, exposed to
      various phenolic compounds (vanillin, gallic acid, and protocatechualdehyde), and
      subjected to linear temperature variation. While the exposure of the SPBs to the
      phenolic compounds did not result in detectable mass density changes, we observed
      noticeable alterations in their gel-fluid phase transitions. It was found that
      QCM-D can detect small variations in a SPB's main transition temperature (?1 
      degrees C) and further resolve compound-specific lipid interactions. The acoustic
      sensing technique thus offers great potential for the use of supported membranes
      as stable and versatile model systems to study the transport of lipid-soluble
      substances into phospholipid bilayers and to assess their interactions therein.

PMID- 30226048
TI  - Steps Control the Dissociation of CO2 on Cu(100).
AB  - CO2 reduction reactions, which provide one route to limit the emission of this
      greenhouse gas, are commonly performed over Cu-based catalysts. Here, we use
      ambient pressure X-ray photoelectron spectroscopy together with density
      functional theory to obtain an atomistic understanding of the dissociative
      adsorption of CO2 on Cu(100). We find that the process is dominated by the
      presence of steps, which promote both a lowering of the dissociation barrier and
      an efficient separation between adsorbed O and CO, reducing the probability for
      recombination. The identification of steps as sites for efficient CO2
      dissociation provides an understanding that can be used in the design of future
      CO2 reduction catalysts.

PMID- 30226049
TI  - Cyanidin-3-O-beta-glucoside, a Natural Polyphenol, Exerts Proapoptotic Effects on
      Activated Platelets and Enhances Megakaryocytic Proplatelet Formation.
AB  - This study investigated whether the anthocyanin cyanidin-3-O-beta-glucoside (Cy-3
      g) could affect platelet apoptosis and proplatelet formation in vitro. Thrombin
      stimulated or resting human platelets and Meg-01 megakaryocytes were incubated
      with Cy-3-g (0, 0.5, 5, or 50 MUM). We found that the percentage of the platelet
      mitochondrial membrane potential treated with 5 and 50 MUM Cy-3-g was
      significantly higher than control (15.50% +/- 3.24% and 29.77% +/- 4.06% versus
      2.76% +/- 1.33%, respectively; P < 0.05). Treatment with 5 and 50 MUM Cy-3-g
      significantly increased phosphatidylserine exposure compared with control (40.56%
      +/- 10.53% and 76.62% +/- 8.28% versus 15.43% +/- 3.93%, respectively; P < 0.05).
      Moreover, Cy-3-g significantly increased the expression of Bax, Bak, and
      cytochrome c while markedly decreasing Bcl-xL and Bcl-2 expression as well as
      stimulating caspase-3, caspase-9, caspase-8, Bid, and gelsolin cleavage in
      thrombin-activated platelets in a dose-dependent manner ( P < 0.05). However, no
      significant differences were observed in the apoptosis of resting platelets when
      treated with Cy-3-g ( P > 0.05). Furthermore, Cy-3-g significantly ( P < 0.05)
      enhanced cell viability (50 MUM versus control, 1.34 +/- 0.01 versus 0.35 +/-
      0.02), the number of colony-forming unit-megakaryocytes (50 MUM versus control,
      38 +/- 3 versus 8 +/- 3), CD41 expression (50 MUM versus control, 96.80% +/-
      2.55% versus 25.57% +/- 2.86%), DNA ploidy (16N) (50 MUM versus control, 19.73%
      +/- 2.34% versus 4.42% +/- 1.96%), and proplatelet formation (50 MUM versus
      control, 27.5% +/- 3.77% versus 7.67% +/- 2.25%) in Meg-01 cells. In conclusion,
      Cy-3-g promotes activated platelet apoptosis and enhances megakaryocyte
      proliferation, differentiation, and proplatelet formation in vitro.

PMID- 30226050
TI  - SnS2 Quantum Dots as New Emitters with Strong Electrochemiluminescence for
      Ultrasensitive Antibody Detection.
AB  - Herein, we designed an electrochemiluminescence (ECL) biosensor with SnS2 quantum
      dots (SnS2 QDs) as novel emitters for the ultrasensitive assay of cytomegalovirus
      pp65 antibody (anti-CMV pp65) via smart circular peptide-DNA nanomachine
      amplification. First, the novel ECL biosensing platform was constructed by self
      assembly of water-soluble, nontoxic, and earth-abundant SnS2 QDs on the 3D
      hierarchical silver nanoflowers (Ag NFs) surface, where the Ag NFs, as coreaction
      accelerator in the ECL ternary (SnS2 QDs/S2O82-/Ag NFs) system, could efficiently
      boost the ECL intensity of SnS2 QDs. Furthermore, we designed a specific nucleic
      acid sequence labeled antigenic peptide to act as multifunctionalized capture
      probe (CP), which could specifically recognize the target antibody assisting with
      two auxiliary DNA strands via the proximity hybridization of DNA motifs to form a
      smart circular peptide-DNA nanomachine. Then, with the aid of nuclease, the
      resultant circular peptide-DNA nanomachine could initiate the subsequent cascade
      recycling amplification to output massive DNA products as mimic target (MT). As a
      result, the proposed ECL biosensor for anti-CMV pp65 detection exhibited high
      sensitivity with a wide linear range from 1 fM to 100 nM and a low detection
      limit (0.33 fM). Importantly, this work not only first utilized SnS2 QDs as
      promising ECL emitters for biosensing platform construction but also opened an
      efficient way for highly sensitive and selective detection of antibody in disease
      diagnosis and clinical analysis.

PMID- 30226051
TI  - First Food-Derived Peptide Inhibitor of the Protein-Protein Interaction between
      Gain-of-Function PCSK9D374Y and the Low-Density Lipoprotein Receptor.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in cholesterol
      homeostasis, because it induces the low-density lipoprotein receptor (LDLR)
      degradation. This protein may carry some positive or negative mutations:
      PCSK9D374Y is one of the most dangerous gain-of-function mutations. This paper
      reports the identification of the first food-derived peptide able to inhibit the
      protein-protein interaction (PPI) between PCSK9D374Y and LDLR. In fact, T9
      (GQEQSHQDEGVIVR), an absorbable peptide deriving from lupin beta-conglutin, is
      able to impair the PPI between PCSK9D374Y and the LDLR, with an IC50 value equal
      to 285.6 +/- 2.46 MUM. The consequence of this inhibition is an increase of the
      protein level of the LDLR located on hepatic cell membranes up to 74.3 +/- 4.4%
      and the restoration of the functional capability of HepG2 cells to uptake
      extracellular low-density lipoprotein up to 83.1 +/- 1.6%. Finally, the putative
      binding mode of T9 to the LDLR binding site located on PCSK9D374Y was postulated
      by in silico tools.

PMID- 30226052
TI  - Helical Hole State in Multiple Conduction Modes in Ge/Si Core/Shell Nanowire.
AB  - Helical states, a prerequisite for the engineering of Majorana zero modes in
      solid-state systems, have recently been reported in the conduction band of III-V
      nanowires (NWs) subject to strong Rashba spin-orbit interaction. We report the
      observation of re-entrant conductance features consistent with the presence of
      helical hole states in multiple conduction modes of a Ge/Si core/shell NW. The
      Ge/Si system has several potential advantages over electron systems such as
      longer spin coherence time due to weaker coupling to nuclear spins and the
      possibility of isotope-purified materials for nuclear spin-free devices. We
      derive the Lande g factor of 3.6 from magneto-transport measurements, comparable
      to theoretical predictions and significantly larger when compared with that in
      strongly confined quantum dots. The spin-orbit energy is evaluated as ~2.1 meV,
      on par with values in III-V NWs, showing good agreement with previous theoretical
      predictions and weak antilocalization measurements.

PMID- 30226053
TI  - Superconductivity in Potassium-Intercalated T d-WTe2.
AB  - To realize a topological superconductor is one of the most attracting topics
      because of its great potential in quantum computation. In this study, we
      successfully intercalate potassium (K) into the van der Waals gap of type II Weyl
      semimetal WTe2 and discover the superconducting state in K xWTe2 through both
      electrical transport and scanning tunneling spectroscopy measurements. The
      superconductivity exhibits an evident anisotropic behavior. Moreover, we also
      uncover the coexistence of superconductivity and the positive magnetoresistance
      state. Structural analysis substantiates the negligible lattice expansion induced
      by the intercalation, therefore suggesting K-intercalated WTe2 still hosts the
      topological nontrivial state. These results indicate that the K-intercalated WTe2
      may be a promising candidate to explore the topological superconductor.

PMID- 30226054
TI  - Updated Global and Oceanic Mercury Budgets for the United Nations Global Mercury
      Assessment 2018.
AB  - In support of international efforts to reduce mercury (Hg) exposure in humans and
      wildlife, this paper reviews the literature concerning global Hg emissions,
      cycling and fate, and presents revised global and oceanic Hg budgets for the 2018
      United Nations Global Mercury Assessment. We assessed two competing scenarios
      about the impacts of 16th - late 19th century New World silver (Ag) mining, which
      may be the largest human source of atmospheric Hg in history. Consideration of Ag
      ore geochemistry, historical documents on Hg use, and comparison of the scenarios
      against atmospheric Hg patterns in environmental archives, strongly support a
      "low mining emission" scenario. Building upon this scenario and other published
      work, the revised global budget estimates human activities including recycled
      legacy emissions have increased current atmospheric Hg concentrations by about
      450% above natural levels (prevailing before 1450 AD). Current anthropogenic
      emissions to air are 2.5 +/- 0.5 kt/y. The increase in atmospheric Hg
      concentrations has driven a ~ 300% average increase in deposition, and a 230%
      increase in surface marine waters. Deeper marine waters show increases of only 12
      25%. The overall increase in Hg in surface organic soils (~15%) is small due to
      the large mass of natural Hg already present from rock weathering, but this
      figure varies regionally. Specific research recommendations are made to reduce
      uncertainties, particularly through improved understanding of fundamental
      processes of the Hg cycle, and continued improvements in emissions inventories
      from large natural and anthropogenic sources.

PMID- 30226055
TI  - Carbon Nanotube Chemical Sensors.
AB  - Carbon nanotubes (CNTs) promise to advance a number of real-world technologies.
      Of these applications, they are particularly attractive for uses in chemical
      sensors for environmental and health monitoring. However, chemical sensors based
      on CNTs are often lacking in selectivity, and the elucidation of their sensing
      mechanisms remains challenging. This review is a comprehensive description of the
      parameters that give rise to the sensing capabilities of CNT-based sensors and
      the application of CNT-based devices in chemical sensing. This review begins with
      the discussion of the sensing mechanisms in CNT-based devices, the chemical
      methods of CNT functionalization, architectures of sensors, performance
      parameters, and theoretical models used to describe CNT sensors. It then
      discusses the expansive applications of CNT-based sensors to multiple areas
      including environmental monitoring, food and agriculture applications, biological
      sensors, and national security. The discussion of each analyte focuses on the
      strategies used to impart selectivity and the molecular interactions between the
      selector and the analyte. Finally, the review concludes with a brief outlook over
      future developments in the field of chemical sensors and their prospects for
      commercialization.

PMID- 30226056
TI  - Walnut ( Juglans regia) Peptides Reverse Sleep Deprivation-Induced Memory
      Impairment in Rat via Alleviating Oxidative Stress.
AB  - The aim of this study was to determine the neuroprotective effects of walnut
      protein hydrolysates (WPH) against memory deficits induced by sleep deprivation
      (SD) in rat and further to identify and characterize the potent neuroprotective
      peptides against glutamate-induced apoptosis in PC12 cells. Results showed that a
      remarkable amelioration effect on behavioral performance in Morris water maze
      test was observed for WPH and its low molecular weight fraction WPHL, especially
      for WPHL. Additionally, a reduction of antioxidant defense (catalase, glutathione
      peroxidase (GSH-px), and superoxide dismutase (SOD)) and an increase of
      malondialdehyde content induced by SD were normalized in brain of rat after oral
      administration of WPH and WPHL. Then three neuroprotective peptides including
      GGW, VYY, and LLPF were identified from WPHL, which could protect PC12 cells
      against glutamate-induced apoptosis with relative cell viability of 78.29 +/-
      3.09%, 80.65 +/- 1.74%, and 83.97 +/- 3.06%, respectively, versus glutamate group
      48.61 +/- 3.99%. The possible mechanism underlying their protective effects of
      GGW and VYY could be related to their strong radical scavenging activity as well
      as their ability to reduce reactive oxygen species production and the depletion
      of SOD and GSH-px in PC12 cells. Notably, the marked neuroprotective effects of
      LLPF, which did not show obvious free-radical scavenging activity in vitro, could
      be attributed to its strong effects on inhibiting Ca2+ influx and mitochondrial
      membrane potential collapse. Additionally, all these peptides could regulate the
      expression of apoptosis-related proteins (Bax and Bcl-2). Therefore, walnut
      peptides might be regarded as the potential nutraceuticals against
      neurodegenerative disorders associated with memory deficits.

PMID- 30226057
TI  - Direct Evidence: Enhanced C2H6 and C2H4 Adsorption and Separation Performances by
      Introducing Open Nitrogen-Donor Sites in a MOF.
AB  - To comparably analyze the influence of a porous environment on the gas adsorption
      in MOFs, based on an imidazole-decorated MOF, {[Zn(imtp)].DMA.1.5H2O} n (1-im,
      H2imtp = 2-(imidazol-1-yl) terephthalic acid), an analogue MOF, {[Zn(tztp)].DMA}
      n (1-tz, H2tztp = 2-(1 H-1,2,4-triazol-1-yl) terephthalic acid) has been
      synthesized by replacing imidazole with triazole motifs. The two MOFs are
      isostructural frameworks containing 1D channels; however, they possess different
      porous wall environments. The open nitrogen-decorated channels in 1-tz lead to
      significantly enhanced C2H6 (76.5 cm3 g-1) and C2H4 (73.1 cm3 g-1) uptakes at 298
      K and 1 atm, which are 5 times of the adsorption amounts of C2H6 and C2H4 in 1-im
      that is the absence of exposed N atoms in the channels. Furthermore, the
      activated 1-tz also reveals higher adsorption selectivities for C2H6 and C2H4
      over CH4. The different sorption properties were further uncovered by theoretical
      simulations.

PMID- 30226058
TI  - 2-Azaadamantane N-oxyl (AZADO)/Cu Catalysis Enables Chemoselective Aerobic
      Oxidation of Alcohols Containing Electron-Rich Divalent Sulfur Functionalities.
AB  - The chemoselective oxidation of alcohols containing electron-rich sulfur
      functionalities (e.g., 1,3-dithianes and sulfides) into their corresponding
      carbonyl compounds with the sulfur groups can sometimes be a demanding task in
      modern organic chemistry. A reliable method for this transformation, which
      features azaadamantane-type nitroxyl radical/copper catalysis using ambient air
      as the terminal oxidant is reported. The superiority of the developed method was
      demonstrated by comparing it with various conventional alcohol oxidation methods.

PMID- 30226059
TI  - A Ferrocene-Based NH-Free Phosphine-Oxazoline Ligand for Iridium-Catalyzed
      Asymmetric Hydrogenation of Ketones.
AB  - A new type of ferrocene-based phosphine-oxazoline ligand has been prepared over a
      few simple steps. An iridium complex of this ligand is air stable and exhibits
      excellent performance for the asymmetric hydrogenation of simple ketones (up to
      98% yield, up to 99% ee, and 20 000 S/C). Exo-alpha,beta-unsaturated cyclic
      ketones could be regiospecifically hydrogenated to give chiral allylic alcohols
      with good results. This study indicates that P,N-ligands can also efficiently
      promote Ir-catalyzed asymmetric hydrogenation without NH-hydrogen-bonding
      assistance.

PMID- 30226061
TI  - Bunte Salt CH2FSSO3Na: An Efficient and Odorless Reagent for
      Monofluoromethylthiolation.
AB  - A practical and efficient monofluoromethylthiolation that employs the typical
      Bunte salt, sodium S-(fluoromethyl) sulfurothioate, as the sulfur source is
      described. This reagent reacts readily with a variety of aryl amines and aryl
      thiols. The high tolerance of functional groups demonstrates the potential of
      this reaction. In addition, this method is suitable for the late-stage
      monofluoromethylthiolation of complex bioactive molecules.

PMID- 30226062
TI  - Oxidative stress in Alzheimer disease as a target for therapy.
AB  - In the recent time, neurodegenerative disorders like Alzheimer disease were
      recognized for their significant role in the current healthcare because of their
      growing incidence and costs for health insurance systems. Effective therapy is
      missing and even etiology of the diseases like Alzheimer disease is not deeply
      known. In the case of Alzheimer disease, it is probable that oxidative stress is
      at least a factor involved in the disease. Nevertheless, the current literature
      is controversial and ambiguous in this matter. This review is focused on mapping
      the role of oxidative stress as well as on a consideration that oxidative stress
      represents the pathway at which a therapeutic strategy can be aimed. This paper
      provides a survey of contemporary literature on oxidative stress in Alzheimer
      disease and discusses the opportunities for establishing a therapy based on
      interfering the stress (Fig. 5, Ref. 117).

PMID- 30226060
TI  - Selective O-Cyclization of N-Methoxy Aryl Amides with CH2Br2 or 1,2-DCE via
      Palladium-Catalyzed C-H Activation.
AB  - A selective O-cyclization of N-methoxy aryl amides with CH2Br2 or 1,2-DCE (1,2
      dichloroethane) via palladium-catalyzed C-H activation has been described. New
      C(sp3)-O and C(sp2)-C(sp3) bonds are forged simultaneously with the assistance of
      an N-methoxy amide group, and good functional group tolerance in substrates is
      observed. Preliminary mechanistic investigations show that the process may
      involve a five-membered palladacycle intermediate.

PMID- 30226063
TI  - The relationship between vitamin D level and organ-specific autoimmune disorders
      in newly diagnosed type I diabetes mellitus.
AB  - INTRODUCTION: The purpose of our study is to determine vitamin D levels in
      patients with newly diagnosed type 1 DM, and assess the association of type 1 DM
      with organ-specific autoimmune disorders, as well as their association with
      vitamin D. MATERIAL AND METHODS: We included a total of 160 patients, of whom 50
      were newly diagnosed with type 1 DM (group I), 50 were formerly diagnosed with
      type 1 DM (group II), and 60 were healthy controls (group III). RESULTS: The mean
      level of 25(OH)D was 14.6 ng/dL in group I, 12.1 ng/dL in group II, and 16.1
      ng/dL in group III. In all diabetic patients, the 25(OH)D levels were lower than
      those of controls. The 25(OH)D median level was 11.4 ng/ml in all cases included
      into the study with ATD. In subjects without ATD, the latter level was 15.3
      ng/ml. The difference was found to be statistically significant. CONCLUSIONS: In
      this study, the vitamin D level was lower in (i) type 1 diabetic patients when
      compared with healthy subjects, (ii) all cases included to study with ATD when
      compared with patients without ATD, (iii) all APA-positive type 1 diabetic
      patients with ATD when compared with none (iv) APA-positive newly diagnosed type
      1 diabetics when compared with those APA-negative (Tab. 7, Fig. 1, Ref. 30).

PMID- 30226064
TI  - Neural derivation of human dental pulp stem cells via neurosphere technique.
AB  - INTRODUCTION: Human dental pulp stem cells (hDPSCs) are multipotent stem cells
      providing an autologous noninvasive cell source. The study evaluates the
      neurogenic potential of hDPSCs using neural growth factor inducers and
      neurosphere technique. METHODS: The hDPSCs were differentiated into neurons using
      neural induction medium containing retinoic acid (RA). Neuroprogenitor cells were
      evaluated for nestin and NF68 using immunocytochemistry. The mature neuron
      markers, MAP-2 and beta-tubulin, were investigated at the end stage of induction
      phase. RESULTS: The neuroprogenitor differentiation was confirmed by
      immunostaining for nestin and NF68 markers. The differentiated neurons were
      positive for specific neuron markers, namely for MAP-2 and beta-tubulin. The
      results indicated that the neural differentiation medium and neurosphere
      technique improve the generation of neuroprogenitor cells as well as mature
      neurons via exhibiting specific neural markers, namely nestin, NF68, MAP-2 and
      beta-tubulin. CONCLUSION: Our findings highlight the differentiation capacity of
      hDPSCs via neurosphere technique in the presence of neural inducers for
      mesenchymal stem cells. It is suggested that the neural differentiation potential
      of hDPSCs can be exploited as a source of stem cells for therapy of
      neurodegenerative diseases (Fig. 5, Ref. 20).

PMID- 30226065
TI  - Biodegradable versus titanium plates and screws for paediatric facial skeleton
      fractures.
AB  - OBJECTIVE: The use of biodegradable materials represents a new option in the
      treatment of paediatric facial skeleton fractures. The benefits of a resorbable
      system include reductions in time for long-term stability, diminished
      immobilisation period, and elimination of painful procedures for implant removal.
      The resorption of the material did not influence bone repair and growth.
      Bioresorbable plates and screws get completely excreted through physiological
      routes. MATERIAL AND METHODS: The age of the patients ranges from that of pre
      schoolers till 18 years. The mean age of boys and girls was 12.18 (range 4-18
      years) and 13.59 (range 5-18 years), respectively. RESULTS: During the ten-year
      period, 168 children and adolescents, 136 boys and 32 girls, were treated. The
      conservative treatment was performed in 67 patients (39.9 %). Open surgical
      reduction was performed in 101 patients (60.1 %). Bioresorbable plates were
      applied in 44 patients (43.6 % of surgically treated). CONCLUSION: The
      implementation of biodegradable osteosynthetic materials is optimal for the
      treatment of fractures of the middle third of the facial skeleton, lower part of
      the upper third of the facial skeleton, mandibular body and parasymphysis (Tab.
      3, Fig. 3, Ref. 31).

PMID- 30226066
TI  - Who needs a permanent pacemaker after transcatheter aortic valve implantation?
AB  - INTRODUCTION: We aimed to identify predictive factors for pacemaker requirement
      and determine the rate of pacemaker dependency in a single centre patient group.
      METHODS AND REULTS: Out of 116 patients, who underwent transcatheter aortic valve
      implantation at our institution. Absence of atrial fibrillation at time of
      procedure, pulmonary hypertension, obesity and severity of aortic valve stenosis
      were predictive for the need of permanent pacemaker implantation after
      transcatheter aortic valve implantation. CONCLUSION: Only persisting
      periprocedural and early-onset complete heart block were permanent and resulted
      in patients' pacemaker dependency. Definite predictors of persistence of
      conduction impairment are yet to be identified. We can predict only pacemaker
      dependency, but the real need of pacing in our risky patients with softer
      indications for permanent pacemaker after transcatheter aortic valve implantation
      cannot be clearly identified, essential in context of improving quality of their
      lives in avoiding symptomatic bradycardia, which can be intermittent, especially
      in such a group of elderly patients often with fragile and degenerate conduction
      system (Tab. 5, Ref. 34).

PMID- 30226067
TI  - Relationship of epicardial fat tissue thickness with oxidant biomarkers in
      chronic kidney disease.
AB  - INTRODUCTION AND OBJECTIVE: IMA and MPO are elevated in serum in case of end
      stage renal disease. Epicardial fat tissue thickness has been considered an
      indicator for cardiovascular diseases recently. The present study was aimed to
      examine the relationship of epicardial fat tissue thickness (EFTT) with IMA and
      MPO levels in patients with CKD. MATERIALS AND METHODS: Predialysis CKD patients
      admitted to the Nephrology outpatient clinic, patients on haemodialysis and
      healthy volunteers were included, 111 patients were in the study. EFTT
      measurement was performed with the transthoracic view using an ECHO device.
      RESULTS: The analysis conducted among the groups in terms of IMA, MPO levels, and
      EFTT revealed a statistically significant difference (p < 0.001). It was
      determined to be the lowest in the healthy volunteers, slightly increased in the
      pre-dialysis group whereas it was quite high in the haemodialysis group.
      According to the correlation test performed, we observed that IMA, MPO levels,
      and EFTT were found to be highly correlated to progression of CKD. CONCLUSION: We
      believe that we have introduced three novel follow-up parameters, such as: IMA,
      MPO, EFTT to literature for the follow-up of CKD. As the levels of IMA MPO and
      EFTT increase, the severity of CKD increases (Tab. 4, Fig. 1, Ref. 25).

PMID- 30226068
TI  - Determination of candidate genes involved in schizophrenia using the whole-exome
      sequencing.
AB  - OBJECTIVES: We used the whole-exome sequencing to evaluate several genes
      suspected of being involved in the pathogenesis of schizophrenia. METHODS: The
      study sample was composed of two families. In the first family, two siblings had
      schizophrenia, and the parents were healthy. In the second family, two siblings
      had schizophrenia, while the other sibling and the parents did not. RESULTS:
      Indels were detected in some genes, including SPON1, GRIA3, SMAD5, PCLO, KMT2C,
      SRD5A2, SEMA3B, NCOR2, GPHB5, FAM174B, CLTCL1, and TMEM216. The insertion of
      three nucleotides (TGA) was detected in the sequence of the PCLO gene. The
      mutation resulted in the insertion of aspartic acid (Asp, D) in the amino acid
      sequence of the PCLO protein. Indels detected in SPON1, GRIA3, SMAD5, KMT2C,
      SRD5A2, SEMA3B, GPHB5, CLTCL1, and TMEM216 were shown to be frameshifting.
      Bioinformatics analysis showed that the indels in SPON1, GRIA3, SMAD5, KMT2C,
      SRD5A2, SEMA3B, NCOR2, GPHB5, FAM174B, CLTCL1, and TMEM216 had a damaging effect,
      while the indel in PCLO had a non-damaging effect on protein function.
      CONCLUSION: To the best of our knowledge, no previous studies have examined the
      relationship between the pathogenesis of schizophrenia and the gene mutations
      identified in this study (Tab. 1, Ref, 42).

PMID- 30226069
TI  - Results of long term testosterone replacement therapy in men with abdominal
      obesity, erectile dysfunction and testosterone deficiency.
AB  - INTRODUCTION: In this article, the authors evaluate subjective and objective
      results of long testosterone replacement therapy (TRT) and possible risk.
      METHODS: In a single center study, the authors treated 69 men with testosterone
      deficiency syndrome (TDS). The average age was 57.84 years and the follow-up
      period was 94.62 months. All men had at beginning a complete urological and
      internal examination. All the men were treated with three-month i.m. injections
      of 1000 mg testosterone undecanoate. The men were regularly checked according to
      the EAU guidelines. RESULTS: All of the men on treatment felt much better. Weight
      and waist circumference during monitoring showed a mild improvement. Excellent
      results were on red blood cells. Glucose, HDL cholesterol, triglycerides had
      stable values. PSA slightly increased and testosterone was within the normal
      range. In two men during treatment, we found a prostate cancer (low risk). Bone
      mineral density (BMD) of lumbar spine revealed a significant improvement.
      CONCLUSION: TRT had multiple positive effect on affected men with TDS. Our long
      term results showed a long mild improvement during the time. Authors concluded
      that long term treatment had multiple benefit for affected men (Fig. 11, Ref.
      13).

PMID- 30226070
TI  - Modulatory effect of 900 MHz radiation on biochemical and reproductive parameters
      in rats.
AB  - In the present study, the effect of 900 MHz radiation exposure on blood
      biochemical and reproductive parameters was evaluated in adolescent rats. Male
      albino Wistar rats (8-10 weeks of age) were exposed to 900 MHz radiation
      (1hr/day, power density - 146.60 uW/cm2) from a mobile phone for 28 days. On 29th
      day the animals were euthanized and malondialdehyde (MDA), total antioxidants
      (TA) levels and Glutathione-S transferase (GST) activity were studied in the
      blood. Reproductive parameters such as total sperm count, percentage of non
      motile sperms, and sperm morphology were determined. Testes sections were stained
      with H(et)E staining and their cellular integrity was evaluated. Caspase-3
      activity in the testes was also determined. MDA concentration was increased but
      TA levels and GST activity were not found to be different in 900 MHz group
      compared to controls. Sperm motility was found to be slightly reduced in 900 MHz
      group. Percentage of abnormal sperm was significantly elevated in 900 MHz group.
      Additionally, loss of germ cells particularly spermatocytes and spermatids was
      found in the testes of 900 MHz group. Testes caspase-3 activity was slightly
      elevated in 900 MHz exposed rats. Chronic 900 MHz exposure induced oxidative
      damage in the blood and lead to alterations in reproductive parameters in rats
      (Fig. 4, Ref. 33).

PMID- 30226071
TI  - The effect of exposure to 1800 MHz radiofrequency radiation on epidermal growth
      factor, caspase-3, Hsp27 and p38MAPK gene expressions in the rat eye.
AB  - OBJECTIVE: Radiofrequency electromagnetic fields (RF-EMF) may induce DNA damage
      and oxidative stress in human lens epithelial cells (LECs). We aimed to
      investigate the expression levels of heat shock protein 27 (Hsp27), p38 mitogen
      activated protein kinase (p38MAPK), epidermal growth factor receptor (EGFR) and
      caspase-3 gene expression levels in rat eye that was exposed to 1800 MHz RF-EMF.
      METHODS: Thirty-seven female Wistar albino rats were divided into three groups.
      The rats in the study group (n = 9) were exposed to 1800 MHz RF-EMF at an
      electric field 6.8 +/- 0.1 V/m and 0.06 W/kg specific absorption rate (SAR) for 2
      hours per day for eight weeks. Sham group (n = 9) was kept under similar
      conditions as the exposed group without exposure to RF-EMF. The rats in all three
      groups were sacrificed and their eyes were removed. Hsp27, p38MAPK, EGFR, caspase
      3 gene expression levels were investigated in detail with real-time polymerase
      chain reactions (Real-Time PCR). RESULTS: caspase-3 and p38MAPK gene expression
      were significantly upregulated in the ocular tissues following exposure to RF-EMF
      (p < 0.05). CONCLUSION: According to our findings, eye cells recognize EMF as a
      stress factor, and in response, activate caspase-3 and p38MAPK gene expressions.
      These results confirm that RF-EMF can cause cellular damage in rat ocular cells
      (Tab. 2, Fig. 3, Ref. 37).

PMID- 30226072
TI  - Effect of carvacrol on IL-6/STAT3 pathway after partial hepatectomy in rat liver.
AB  - BACKGROUND: Carvacrol is a component in the essential oil of Lamiaceae family.
      Beside its antihepatotoxic and hepatoprotective properties it is known to be a
      contribution to liver regeneration. OBJECTIVES: This study aimed to investigate
      the effects of carvacrol in rat liver regeneration after 70 % partial hepatectomy
      (PHx) through interleukin-6 (IL-6)/signal transducer and activator of
      transcription 3 (STAT3) and mitogen-activated protein kinases (MAPK) pathways.
      METHODS: In our study six groups were formed from 3-month old Wistar albino male
      rats. Group I and II were Sham operated; Group III and IV received 1 mL 0.9 %
      NaCl; and Group V and VI were the groups that were treated with 73 mg/kg
      carvacrol. Group III, IV, V, and VI animals underwent 68-70 % PHx. Dissection was
      performed 24 and 48 after surgical procedure. Serum Alanine transaminase (ALT)
      levels were determined. The liver regeneration rate (RR) was calculated.
      Histopathological analysis was performed by Hematoxylin(et)Eosin staining and the
      proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemical
      staining in liver samples. In the liver, certain genes expressions in IL-6/STAT3
      and MAPK pathways with RT-PCR analysis and protein expression with Western blot
      analysis were measured. CONCLUSION: Carvacrol showed a positive effect on
      hepatocyte proliferation and liver regeneration 24 and 48 hours after PHx (Tab.
      1, Fig. 7, Ref. 39).

PMID- 30226073
TI  - The effects on peripheral nerve damage of the application of local and systemic
      erythropoietin.
AB  - OBJECTIVE: To investigate the histopathological and biochemical effects of
      topical and systemic administrations of erythropoietin (EPO) on crush and
      transection type peripheral nerve injuries in an experimental rat model. METHODS:
      128 male Wistar-Albino rats were allocated to 8 groups according to the route of
      administration of EPO (local/systemic) and type of peripheral nerve injury
      (crush/transection). groups were compared with respect to histopathological
      examination and number of axons as well as levels of IL-1beta, IL-6, and IL-10.
      RESULTS: Groups receiving EPO either locally or intraperitoneally revealed less
      scar tissue formation index, lower number of inflammatory cells, reduced number
      of perineural fibroblasts and increased number of axons (p < 0.001 for all).
      Levels of IL-1beta and IL-6 were lower and IL-10 levels were higher in groups
      receiving EPO locally or intraperitoneally (p < 0.001). CONCLUSION: Iatrogenic
      nerve injury has remained an area with few therapeutic options. Our results
      indicated that local and systemic applications of EPO might have a promising
      potential therapeutic agent for crush or transection type of peripheral nerve
      injuries. Dose, route of administration and indications should be elucidated in
      further prospective, randomized, controlled trials (Tab. 3, Fig. 4, Ref. 32).

PMID- 30226074
TI  - Quality of life, demoralization syndrome and health-related lifestyle in cardiac
      transplant recipients - a longitudinal study in Taiwan.
AB  - BACKGROUND: Quality of life is an outcome indicator after health care treatment,
      and the factors that affect quality of life change over time after heart
      transplantation. As such, quality of life as related to heart transplantation
      warrants further investigation. AIMS: The purposes of this study were to compare
      different post-transplant times of cardiac transplant recipients in terms of
      their quality of life, demoralization syndrome and health-related lifestyle and
      to identify the predictors of quality of life in Taiwan. METHODS: This
      longitudinal study, which used convenience sampling, was conducted in one medical
      center. Participants were divided into three groups (1, 2 and 3) based on post
      transplant time. Four questionnaires, that is, demographic, quality of life,
      including a physical and mental component summary (PCS and MCS), demoralization
      and health-related lifestyle, were used to collect data at baseline and at three,
      six and 12 months. Hierarchical regression was used to identify the predictors of
      quality of life. RESULTS: There were 99 participants, who were divided into three
      groups: Group 1 ( n = 31), Group 2 ( n = 29) and Group 3 ( n = 39). The majority
      of participants were male, with a mean age of 53.68 years. In each group, fewer
      than half had good quality of life, and one-third had demoralization syndrome.
      Demoralization syndrome combined with post-transplant time, age, use of
      mechanical circulatory support during hospitalization and stress status accounted
      for 35.2% of PCS for all participants. Further, demoralization syndrome combined
      with age and religion accounted for 40.3% of MCS for all participants.
      CONCLUSIONS: The results indicated that quality of life, demoralization syndrome
      and health-related lifestyle were correlated over time. Demoralization was an
      independent predictor of quality of life.

PMID- 30226076
TI  - Surface Chemistry of Oil-Filled Organic Nanoparticle Coated Papers Analyzed Using
      Micro-Raman Mapping.
AB  - Raman spectroscopy and micro-Raman mapping have been used to study the
      distribution of different chemical components at the surface of coated papers.
      The paper coatings contain organic nanoparticles with a structure of poly(styrene
      co-maleimide) and encapsulated vegetable oils. Raman spectroscopy is able to
      differentiate between various types of oil, i.e., polyunsaturated,
      monounsaturated, or saturated, and indicates that the degree of imidization and
      reactivity of the oil (amount of free oil) complement each other. The surface
      mapping over large areas (5 * 5 mm2) illustrates good homogeneity of the coating
      layer and even surface coverage. The imide and oil are homogeneously distributed
      within the coating itself without a tendency for agglomeration. The covered areas
      of imide and oil mostly overlap for polyunsaturated oils, while larger amounts of
      oil occur outside the imide zones for monounsaturated and saturated oils. The
      latter indicates that the oil is partly "free" within the coating and acts as a
      continuous binder phase. The surface mapping over smaller areas (1 * 1 mm2) shows
      the coating and cellulose covered areas are complementary. The surface maps
      confirm that interaction between the coating and paper substrate happens through
      hydrogen bonding. Heterogeneities in the coating are due to the presence of
      remaining ammonolyzed maleic anhydride precursors forming amic acid moieties. The
      organic phase, oil phase, and cellulose substrate can also be differentiated by
      principal component analysis of the surface maps.

PMID- 30226075
TI  - A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of
      the Proteins Secreted by Human Adipose-Derived Mesenchymal Stem Cells.
AB  - Liquid chromatography using a tandem mass spectrometer (LC-MS/MS) is a method of
      proteomic analysis. A shotgun analysis by LC-MS/MS comprehensively identifies
      proteins from tissues and cells with high resolution. The hepatic function of
      mice with acute hepatitis following the intraperitoneal administration of CCL4
      was improved by the tail vein administration of the culture conditional medium
      (CM) of human mesenchymal stem cells from adipose tissue (hMSC-AT). In this
      study, a secreted protein expression analysis of hMSC-AT was performed using LC
      MS/MS; 128 proteins were identified. LC-MS/MS showed that 106 new functional
      proteins and 22 proteins (FINC, PAI1, POSTN, PGS2, TIMP1, AMPN, CFAH, VIME, PEDF,
      SPRC, LEG1, ITGBL, ENOA, CSPG2, CLUS, IBP4, IBP7, PGS1, IBP2, STC2, CTHR1, CD9)
      were previously reported in hMSC-AT-CMs. In addition, various proteins associated
      with growth (SAP, SEM7A, PTK7); immune system processes (CO1A2, CO1A1, CATB,
      TSP1, GAS6, PTX3, C1 S, SEM7A, G3P, PXDN, SRCRL, CD248, SPON2, ENPP2, CD109,
      CFAB, CATL1, MFAP5, MIF, CXCL5, ADAM9, CATK); and reproduction (MMP2, CATB,
      FBLN1, SAP, MFGM, GDN, CYTC) were identified in hMSC-AT-CMs. These results
      indicate that a comprehensive expression analysis of proteins by LC-MS/MS is
      useful for investigating new factors associated with cellular components,
      biological processes, and molecular functions.

PMID- 30226077
TI  - Synthetic cannabinoids in biological specimens: a review of current analytical
      methods and sample preparation techniques.
AB  - Synthetic cannabinoids are a new class of chemical drugs capable of modifying
      human behavior. These products do not contain cannabis, but produce similar
      effects after consumption. The fact that they are easily accessed, and are many
      times considered to be harmless, justifies their widespread use among young
      people. This fact, together with the difficulty in their detection by routine
      drug tests, makes it extremely important to develop new procedures able to detect
      and monitor their consumption. The aim of this work is to perform a critical
      review regarding the human biological samples that can be used for the
      determination of synthetic cannabinoids, paying special attention to analytical
      methods and sample preparation techniques. The reviewed articles deal with the
      determination of synthetic cannabinoids in the context of forensic and
      toxicological analysis.

PMID- 30226078
TI  - An exploration of self-compassion and self-criticism in the context of personal
      recovery from borderline personality disorder.
AB  - OBJECTIVES: A lack of compassion for oneself, or harsh self-criticism, is
      associated with a range of psychiatric disorders including borderline personality
      disorder (BPD). Personal recovery in the context of a mental illness such as BPD
      involves building a life that is subjectively meaningful and satisfying. Limited
      self-compassion or harsh self-criticism may be an impediment to recovery from
      BPD. The association between self-compassion and recovery and self- criticism and
      recovery were examined. METHOD: Nineteen individuals diagnosed with BPD completed
      the Neff Self-Compassion Scale, the Forms of Self-Criticising/Attacking and Self
      Reassuring Scale and the Recovery Assessment Scale at a single time point.
      RESULTS: There was a strong positive correlation between self-compassion and
      recovery ( r = 0.75) and a strong negative correlation ( rho = -0.67) between
      self- criticism and recovery. CONCLUSIONS: Although preliminary in nature, these
      results suggest the importance of fostering self-compassion and working to
      address self-criticism within clinical interventions supporting recovery from
      BPD.

PMID- 30226079
TI  - Using Technology to Conduct Focus Groups With a Hard-to-Reach Population: A
      Methodological Approach Concerning Male Victims of Partner Abuse in Four English
      Speaking Countries.
AB  - Research shows that the experiences of male victims of partner abuse (PA) are
      often denied by the public and the professionals who are charged to support PA
      victims. Recruiting female victims for research on PA victimization is relatively
      easy because there are existing structures to serve this group of victims. Thus,
      male victims are considered a hard-to-reach (HTR) population, and studying them
      can be difficult. This article focuses on the use of technology to collect
      qualitative data from male PA victims in an international study focusing on male
      victims. The researchers used their own professional networks to recruit and
      screen a convenience sample of male victims of female-to-male PA, in four
      different English-speaking countries: Australia, Canada, England, and the United
      States. Four web-based, video-enabled, focus groups were held for each country
      for a total of 12 groups and 41 male participants. This article addresses
      recruitment methods, the use of technology in data collection, protecting the
      confidentiality of male victims, methods for informed consent, and lessons
      learned to facilitate future research.

PMID- 30226080
TI  - Basement membrane and stroke.
AB  - Located at the interface of the circulation system and the CNS, the basement
      membrane (BM) is well positioned to regulate blood-brain barrier (BBB) integrity.
      Given the important roles of BBB in the development and progression of various
      neurological disorders, the BM has been hypothesized to contribute to the
      pathogenesis of these diseases. After stroke, a cerebrovascular disease caused by
      rupture (hemorrhagic) or occlusion (ischemic) of cerebral blood vessels, the BM
      undergoes constant remodeling to modulate disease progression. Although an
      association between BM dissolution and stroke is observed, how each individual BM
      component changes after stroke and how these components contribute to stroke
      pathogenesis are mostly unclear. In this review, I first briefly introduce the
      composition of the BM in the brain. Next, the functions of the BM and its major
      components in BBB maintenance under homeostatic conditions are summarized.
      Furthermore, the roles of the BM and its major components in the pathogenesis of
      hemorrhagic and ischemic stroke are discussed. Last, unsolved questions and
      potential future directions are described. This review aims to provide a
      comprehensive reference for future studies, stimulate the formation of new ideas,
      and promote the generation of new genetic tools in the field of BM/stroke
      research.

PMID- 30226081
TI  - Measurement of splenic stiffness by 2D-shear wave elastography in patients with
      extrahepatic portal vein obstruction.
AB  - OBJECTIVE:: To assess the accuracy of splenic stiffness (SS) measured by 2D-shear
      wave elastography (SWE) for predicting variceal bleeding in the patients with
      extrahepatic portal vein obstruction (EHPVO). METHODS:: 52 patients with EHPVO
      (mean age: 22.29 years; 26 each males and females) were included in the study
      after obtaining approval from the institute ethics committee. All patients
      initially underwent upper gastrointestinal endoscopy followed by ultrasonography,
      including 2D-SWE on the Aixplorer Supersonic Imagine scanner. The SS was measured
      through the anterior abdominal wall and an average of three measurements was
      taken. The SS was then compared with clinical symptoms, variceal grade, and other
      ultrasonography (USG) parameters. USG parameters were also compared with variceal
      grade. RESULTS:: The mean SS was 44.92 +/- 12.35 kPa. There was no significant
      difference in the mean SS of patients with high grade varices (44.30 kPa; n = 25)
      from those with low grade varices (46.91 kPa; n = 20). The ROC analysis showed a
      poor area under the curve of 0.477 for the prediction of high grade varices by
      the SS. The SS did not show any significant correlation with other
      ultrasonography parameters except splenic size, with which there was a weak but
      significant correlation. The measurement of SS by 2D-SWE was reliable and
      Cronbach's alpha was 0.905. CONCLUSION:: The SS measured by 2D-SWE is not an
      accurate predictor of variceal grade and thus bleeding in patients of EHPVO.
      ADVANCES IN KNOWLEDGE:: EHPVO is a vascular pathology with most patients showing
      splenomegaly and preserved liver function. Although, elastography of spleen has
      been shown to be useful in patients with cirrhosis for predicting portal
      hypertension, it does not seem to be helpful in patients with EHPVO.

PMID- 30226082
TI  - Superior Performance in Prone in Infants With Congenital Heart Disease Predicts
      an Earlier Onset of Walking.
AB  - Infants with congenital heart disease are at risk of impaired neurodevelopment,
      which frequently manifests as motor delay during their first years of life. This
      delay is multifactorial in origin and environmental factors, such as a limited
      experience in prone, may play a role. In this study, we evaluated the motor
      development of a prospective cohort of 71 infants (37 males) with congenital
      heart disease at 4 months of age using the Alberta Infant Motor Scales (AIMS). We
      used regression analyses to determine whether the 4-month AIMS scores predict the
      ability to walk by 18 months. The influence of demographic and clinical variables
      was also assessed. Fifty-one infants (71.8%) were able to maintain the prone prop
      position (AIMS score of >=3 in prone) at 4 months. Of those, 47 (92.2%) were able
      to walk by 18 months compared to only 12/20 (60%) of those who did not maintain
      the position. Higher AIMS scores were predictive of a greater likelihood of
      walking by 18 months ( P < .001), with the scores in prone having a higher
      predictive ability compared to those in other positions (Exp(B) 15.2 vs 4.0).
      Shorter hospital stays and female gender were also associated with an earlier
      onset of walking. In conclusion, our study demonstrates that early ventral
      performance in infants with congenital heart disease impacts the age of
      acquisition of walking and could be used to guide referral to rehabilitation.

PMID- 30226083
TI  - Specificity versus selectivity: twin aims of aptasensors in bioanalysis.

PMID- 30226085
TI  - HIV-Related Knowledge in PLHIV: Issues to Consider in the Indian Context-A Reply
      to Banagi Yathiraj et al.

PMID- 30226084
TI  - An improved LC-MS/MS method for simultaneous evaluation of CYP2C9, CYP2C19,
      CYP2D6 and CYP3A4 activity.
AB  - AIM: To develop an LC-MS/MS assay to quantitate well-tolerated substrates;
      midazolam (CYP3A), omeprazole (CYP2C19), dextromethorphan (CYP2D6), losartan
      (CYP2C9) and their respective metabolites' concentrations in plasma samples.
      PATIENTS & METHODS: A solid-phase extraction method was optimized to extract
      analytes of interest simultaneously from human plasma samples. The assay analyzed
      plasma samples collected from patients who received equal or lower than
      therapeutic doses of CYP substrates. RESULTS: This assay was validated based on
      the European Medicines Agency guideline for bioanalytical method validation and
      was sensitive, linear, accurate and precise with acceptable recovery and matrix
      effects. CONCLUSION: Small sample volume and dose of cytochrome P450 substrates,
      short-run time, using stable isotope internal standards and being cost effective
      are the major advantages of the assay.

PMID- 30226086
TI  - EBF recommendation on practical management of critical reagents for PK ligand
      binding assays.
AB  - Critical reagents play a crucial role in ligand-binding assays; the robustness
      and reliability of an assay is defined by the quality and long-term availability
      of these reagents. However, neither regulatory guidelines nor relevant scientific
      papers provide clear directions for set-up, life cycle management and, more
      importantly, the acceptance criteria required for the testing of the critical
      reagents for pharmacokinetic, biomarker and immunogenicity assays. The ambiguity
      from current guidelines can be a challenge for the bioanalytical community.
      Members of the European Bioanalysis Forum community undertook a more pragmatic
      approach on how to assess the impact of critical reagents. In this paper, a
      review and corresponding gap analysis of the current guidelines and relevant
      papers will be provided as well as decision trees proposed for lot-to-lot changes
      of critical reagents for pharmacokinetic assays.

PMID- 30226087
TI  - No interaction between rivastigmine and citalopram on memory and novelty
      processing in healthy human volunteers.
AB  - BACKGROUND: Animal literature suggests an interaction between acetylcholine and
      serotonin on cognitive functions. AIMS: The aim of the current study was to
      assess whether both neurotransmitters interact during memory and novelty
      processing in humans. METHODS: We tested the interaction between acetylcholine
      and serotonin on cognitive functions in healthy volunteers by means of treatment
      with rivastigmine and citalopram, respectively. RESULTS: The main result of the
      study showed that during the verbal learning task participants significantly
      recalled fewer words after citalopram treatment than after rivastigmine or
      placebo during both the immediate and delayed recall tasks. Rivastigmine was not
      able to reverse the impairing effect of citalopram. CONCLUSIONS: This finding is
      in line with previous studies in which we manipulated acetylcholine and serotonin
      in different manners. Taken together, these studies in humans do not support the
      notion from animal studies that these two neurotransmitters interact on cognitive
      functions.

PMID- 30226088
TI  - The Differential Role of Narcissism in the Relations Between Childhood Sexual
      Abuse, Dissociation, and Self-Harm.
AB  - Childhood sexual abuse (CSA) is considered a risk factor for self-harm behaviors.
      According to the anti-dissociation model of self-harm, the relation between CSA
      and self-harm is mediated by dissociation. However, inconclusive evidence
      supporting this model suggests that this association may be moderated by
      vulnerability factors. Grandiose and vulnerable narcissism represent distinct
      patterns of behaviors intended to deal with unmet needs of recognition. The aim
      of the study was to examine a model in which the relation between CSA and self
      harm is mediated by dissociation, and the relation between dissociation and self
      harm is moderated by grandiose narcissism and vulnerable narcissism. A battery of
      self-reported questionnaires including the Childhood Trauma Questionnaire,
      Dissociative Experiences Scale, Deliberate Self-Harm Inventory, and Brief
      Pathological Narcissism Inventory were filled out by 766 college/university
      students. Results indicated that self-harm was related to CSA through the
      mediation of dissociation. Moreover, the analyses yielded significant
      interactions of both vulnerable and grandiose narcissism with dissociation in
      predicting self-harm; the relation between dissociation and self-harm was
      significant among individuals with high levels of vulnerable narcissism, as well
      as among individuals with low levels of grandiose narcissism. These findings
      support the anti-dissociation model of self-harm. The findings also highlight the
      complex and ambiguous role of narcissism in the long-term adjustment of CSA
      survivors.

PMID- 30226089
TI  - Targeting the CD47-SIRPalpha signaling axis: current studies on B-cell lymphoma
      immunotherapy.
AB  - The function of the immune system in cancer initiation and progression has been
      widely examined. Notably, immunotherapy has become a promising approach for
      cancer treatment. CD47, a member of the immunoglobulin superfamily, plays an
      important role in the immune regulation of cancer by binding to SIRPalpha.
      Multiple studies have detected high CD47 expression on the surface of tumor
      cells, which indicates poor prognosis. Treatments that block the interaction of
      CD47 and SIRPalpha significantly suppress tumor growth and metastasis through
      diverse mechanisms, such as phagocytosis, antibody-dependent cellular
      cytotoxicity, and apoptosis. Recently, several studies have reported increased
      CD47 expression on different types of lymphoma cells, indicating that the CD47
      SIRPalpha pathway can be used as a therapeutic target in lymphoma. This review
      focuses on the role of CD47-SIRPalpha in B-cell lymphoma and discusses promising
      therapeutic strategies targeting the CD47-SIRPalpha axis, which yield insights
      into the immunotherapy of B-cell lymphoma.

PMID- 30226090
TI  - Response Rates of Medical Providers to Internet Surveys Regarding Their Adoption
      of Preexposure Prophylaxis for HIV: Methodological Implications.
AB  - In 2016 to 2017, we surveyed primary care providers (PCPs) in upper Manhattan and
      the South Bronx, New York, on their knowledge, attitudes, and practices
      surrounding preexposure prophylaxis (PrEP) for HIV. Despite efforts to promote
      survey response, we were only able to obtain a meager response rate, limiting our
      ability to interpret results. In this short communication, we examine our
      survey's methodology, as well as the methods used by other similar studies, in
      order to suggest how certain strategies appear to influence PCP response to PrEP
      surveys. Administering the survey in a variety of modes, sampling from a
      professional organization's listserv, promoting the survey topic's relevance to
      potential participants, and offering monetary incentives to each survey
      respondent all appear to be promising strategies for increasing response rates in
      PrEP provider surveys.

PMID- 30226091
TI  - Paraneoplastic Phenomena in a Patient With Locally Destructive and Metastatic
      Renal Cell Carcinoma.
AB  - Renal cell carcinoma (RCC) accounts for approximately 80% of all primary renal
      neoplasms in United States causing approximately 65 000 new cases of RCC and 14
      000 deaths each year. Symptoms of RCC typically include weight loss and night
      sweats but may also feature paraneoplastic phenomena in advanced stages as well
      as flank pain, gross hematuria, scrotal varicocele, inferior vena cava pathology,
      and a palpable abdominal mass. In this article, we present the course of a
      patient with advanced RCC, from initial presentation through workup and to
      eventual diagnosis. The case features late-onset symptoms, extensive
      paraneoplastic phenomena, and significant physical examination findings. We also
      review the literature available on RCC and critically analyze inefficiencies of
      the workup retrospectively.

PMID- 30226092
TI  - Compassion Satisfaction to Combat Work-Related Burnout, Vicarious Trauma, and
      Secondary Traumatic Stress.
AB  - Helping professionals play an essential role in the recovery of victims of
      trauma. However, research has demonstrated that, as a result of their work,
      helping professionals' indirect exposure to clients' trauma increases the
      likelihood of experiencing negative psychological responses, including vicarious
      trauma (VT), secondary traumatic stress (STS), and burnout. The present study
      examined the concurrent validity between the STS subscale on the Professional
      Quality of Life (ProQoL) scale and the Secondary Traumatic Stress Scale (STSS).
      Furthermore, the relationships between compassion satisfaction (CS) and burnout
      were investigated. Participants were recruited using a comprehensive web search
      of agencies across the United States that employed victim advocates, a subtype of
      helping professionals that are understudied. A list of possible agencies ( N =
      75) was generated, and each agency was sent an email about the study. In total,
      132 victim advocates provided data for these analyses. Findings revealed positive
      correlations between the STS subscale on the ProQoL and the STSS. In addition, a
      negative correlation was found between burnout and CS. Two-level hierarchical
      multiple regression analyses demonstrated that burnout accounted for 47.3% of the
      variance in STS, and CS contributed an additional 3.9%. Furthermore, burnout
      accounted 45.8% of the variance in VT, whereas CS contributed an additional 0.6%,
      indicating that burnout is a strong predictor of VT and STS, but CS may serve as
      a protective factor against experiencing both. Prevention and intervention
      efforts should target reducing burnout to combat these psychological sequelae and
      increasing CS.

PMID- 30226093
TI  - Transparency in scientific publication: time for a new negotiated settlement?

PMID- 30226095
TI  - Claude Bernard, statistics and comparative trials.

PMID- 30226097
TI  - Winston Churchill's cerebrovascular disease: small vessels with big implications.

PMID- 30226098
TI  - Understanding career barriers for women in surgery.

PMID- 30226100
TI  - The Promise of Electronic Health Records to Promote Shared Decision Making: A
      Narrative Review and a Look Ahead.
AB  - BACKGROUND: Shared decision making (SDM) involves the sharing of best available
      evidence between patients and providers in the face of difficult decisions. We
      examine outcomes that occur when electronic health records (EHRs) are
      purposefully used with the goal of improving SDM and detail which EHR functions
      can benefit SDM. METHODS: A systematic search of PubMed yielded 1369 articles.
      Studies were included only if they used EHR interventions to support SDM and
      included results that showed impact on SDM. Articles were excluded if they did
      not measure the impact of the intervention on SDM or did not discuss how SDM had
      been supported by the EHR. RESULTS: Five studies demonstrated improved clinical
      outcomes, positive lifestyle behavior changes, more deliberation from patients
      regarding use of imaging, and less decisional conflict about medication use among
      patients with use of EHRs aiding SDM. DISCUSSION: Few EHRs have integrated SDM,
      and even fewer evaluations of these exist. EHRs have potential in supporting
      providers during all steps of SDM. The promise of EHRs to support SDM has yet to
      be fully exploited.

PMID- 30226101
TI  - Mapping the EORTC-QLQ-C30 to the EQ-5D-3L: An Assessment of Existing and Newly
      Developed Algorithms.
AB  - OBJECTIVES: To assess the external validity of mapping algorithms for predicting
      EQ-5D-3L utility values from EORTC QLQ-C30 responses not previously validated and
      to assess whether statistical models not previously applied are better suited for
      mapping the EORTC QLQ-C30 to the EQ-5D-3L. METHODS: In total, 3866 observations
      for 1719 patients from a longitudinal study (Cancer 2015) were used to validate
      existing algorithms. Predictive accuracy was compared to previously validated
      algorithms using root mean squared error, mean absolute error across the EQ-5D-3L
      range, and for 10 tumor-type specific samples as well as using differences
      between estimated quality-adjusted life years. Thirteen new algorithms were
      estimated using a subset of the Cancer 2015 data (3203 observations for 1419
      patients) applying various linear, response mapping, beta, and mixture models.
      Validation was performed using 2 data sets composed of patients with varying
      disease severity not used in the estimation and all available algorithms ranked
      on their performance. RESULTS: None of the 5 existing algorithms offer an
      improvement in predictive accuracy over preferred algorithms from previous
      validation studies. Of the newly estimated algorithms, a 2-part beta model
      performed the best across the validation criteria and in data sets composed of
      patients with different levels of disease severity. Validation results did,
      however, vary widely between the 2 data sets, and the most accurate algorithm
      appears to depend on health state severity as the distribution of observed EQ-5D
      3L values varies. Linear models performed better for patients in relatively good
      health, whereas beta, mixture, and response mapping models performed better for
      patients in worse health. CONCLUSION: The most appropriate mapping algorithm to
      apply in practice may depend on the disease severity of the patient sample whose
      utility values are being predicted.

PMID- 30226102
TI  - Risk and Resilience Factors for Psychobehavioral Symptom Trajectories Among Child
      Welfare-Involved Youth.
AB  - The primary aim of the study was to investigate the development of
      psychobehavioral symptoms (internalizing, externalizing, and posttraumatic stress
      [PTS]) of child welfare-involved adolescents over a 3-year period and to identify
      predictors of the trajectories. Using three waves of data from the National
      Survey of Child and Adolescent Well-Being (NSCAW-II), latent growth curve
      modeling was conducted on a sample of 350 adolescents who were between 11 and 13
      years of age at baseline. Findings indicated that adolescents' internalizing
      symptoms decreased over time, whereas externalizing symptoms remained stable over
      time. PTS symptoms decreased over time in girls, but not boys. Physical abuse
      predicted higher levels of externalizing behaviors and sexual abuse predicted a
      slower decrease in PTS symptoms. Greater child prosocial skills and higher
      quality of caregiver-child relationship were associated with lower initial levels
      of externalizing symptoms. In addition, a higher quality caregiver-child
      relationship and greater satisfaction with peer relationships were associated
      with lower initial levels of internalizing and PTS symptoms. Findings suggest
      that intervention strategies should consider gender, maltreatment type, and
      interpersonal and social skills to effectively prevent the development of
      psychobehavioral symptoms among child welfare-involved youth.

PMID- 30226103
TI  - Deciphering the paradoxical incidence of cancer in schizophrenia.
AB  - OBJECTIVES:: The incidence of cancer in schizophrenia has been an area of
      controversy. The current article aims to provide a commentary outlining the
      contradictory findings of incidence of cancer in schizophrenia as well as discuss
      the available theories linking cancer with schizophrenia and address the
      methodological issues of the studies which could lead to the discrepant findings.
      METHOD:: A literature search was carried out primarily using the electronic
      database of MEDLINE through PubMed using the search terms 'cancer' and
      'schizophrenia'. Google Scholar was used to supplement the search. RESULTS:: The
      findings were inconclusive, with studies documenting increased, decreased as well
      as no risk of cancer in patients with schizophrenia, compared with the general
      population. Several methodological limitations exist with regard to measures of
      assessment, sample size and selection bias. CONCLUSIONS:: The association between
      cancer and schizophrenia remains controversial. Genetic as well as environmental
      theories exist explaining the paradoxical incidence of cancer in schizophrenia.
      The methodological factors could contribute to the discrepant findings.

PMID- 30226104
TI  - Obtaining consent for non-psychiatric treatment of persons detained under mental
      health legislation in Australia and New Zealand: is there cross-jurisdictional
      consistency?
AB  - OBJECTIVE: It is increasingly recognised that persons with mental illness
      experience physical health issues at greater rates than the general population
      and that there are significant barriers to accessing appropriate treatment. One
      less obvious barrier to appropriate care may be the law. This review examines the
      legal regimes within Australia and New Zealand that regulate consent for medical
      and surgical treatment for persons detained under mental health legislation. The
      review begins with a brief overview of concepts of consent and capacity then
      examines the law with regards to consent for non-psychiatric treatment for
      persons detained in psychiatric facilities. The complexity and cross
      jurisdictional consistency is considered and potential future directions and
      possibilities for reform are discussed. CONCLUSION: Examination of the different
      laws regarding consent for medical or surgical treatment for persons admitted to
      psychiatric facilities are complex and demonstrate lack of consistency across
      jurisdictions. Reform in this area might be considered to achieve greater
      consistency and clarity for both health professionals and consumers.

PMID- 30226105
TI  - Do police-mental health co-responder programmes reduce emergency department
      presentations or simply delay the inevitable?
AB  - OBJECTIVE: The aim of this study was to assess the outcomes for people following
      intervention by a police-mental health co-responder team. METHOD: Individuals
      seen by the co-responder team were followed for 2 weeks to monitor subsequent
      emergency department presentations and inpatient admissions. RESULTS: Of the 122
      people who had direct contact with the co-responder team, 82 (67.2%) remained at
      their residence, 35 (28.7%) were transported to the emergency department (ED) and
      5 (4.1%) were taken into custody by police. The 82 people who remained at home
      following initial assessment were followed-up for 2 weeks. During this time 10
      (12.2%) presented to ED and 3 of these (3.7%) were subsequently admitted to
      hospital. CONCLUSIONS: Interventions provided through the co-responder team were
      capable not only of resolving the immediate crisis for the majority of people,
      but were also likely to divert people away from ED and inpatient treatment in the
      immediate term.

PMID- 30226106
TI  - A pilot study examining the profile of older people on clozapine.
AB  - OBJECTIVE:: The primary aim was to comprehensively describe the characteristics
      of a cohort of older people taking clozapine. METHOD:: Participants aged ? 60 had
      a geriatric assessment including full medical, medication and social history.
      Standardized screening tools for cognition, function, comorbidity and
      antipsychotic side effects were administered and descriptive statistics utilized.
      RESULTS:: Thirteen patients were eligible to participate and 10 were assessed.
      The mean age was 69 years. The mean clozapine dose was 309 mg/day and mean
      duration of use was 10 years. All participants had executive dysfunction, and
      half had cognitive impairment. The mean number of co-morbid conditions was five.
      Seven people met the criteria for polypharmacy. Eight people experienced moderate
      severe antipsychotic-related side-effects. The majority demonstrated impaired
      physical functioning. CONCLUSIONS:: This cohort of older people taking clozapine
      experienced considerable morbidity, functional and cognitive impairment. We
      suggest routine screening of cognition and function in clozapine patients aged ?
      60 years. Those screening positive should be considered for further assessment by
      Older Person's Mental Health Services and/or a Geriatric Medicine service.

PMID- 30226107
TI  - The tryptophan derivative 6-formylindolo[3,2-b]carbazole, FICZ, a dynamic
      mediator of endogenous aryl hydrocarbon receptor signaling, balances cell growth
      and differentiation.
AB  - The aryl hydrocarbon receptor (AHR) is not essential to survival, but does act as
      a key regulator of many normal physiological events. The role of this receptor in
      toxicological processes has been studied extensively, primarily employing the
      high-affinity ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However,
      regulation of physiological responses by endogenous AHR ligands remains to be
      elucidated. Here, we review developments in this field, with a focus on 6
      formylindolo[3,2-b]carbazole (FICZ), the endogenous ligand with the highest
      affinity to the receptor reported to date. The binding of FICZ to different
      isoforms of the AHR seems to be evolutionarily well conserved and there is a
      feedback loop that controls AHR activity through metabolic degradation of FICZ
      via the highly inducible cytochrome P450 1A1. Several investigations provide
      strong evidence that FICZ plays a critical role in normal physiological processes
      and can ameliorate immune diseases with remarkable efficiency. Low levels of FICZ
      are pro-inflammatory, providing resistance to pathogenic bacteria, stimulating
      the anti-tumor functions, and promoting the differentiation of cancer cells by
      repressing genes in cancer stem cells. In contrast, at high concentrations FICZ
      behaves in a manner similar to TCDD, exhibiting toxicity toward fish and bird
      embryos, immune suppression, and activation of cancer progression. The findings
      are indicative of a dual role for endogenously activated AHR in barrier tissues,
      aiding clearance of infections and suppressing immunity to terminate a vicious
      cycle that might otherwise lead to disease. There is not much support for the AHR
      ligand-specific immune responses proposed, the differences between FICZ and TCDD
      in this context appear to be explained by the rapid metabolism of FICZ.

PMID- 30226108
TI  - A tale of two demyelinating diseases and Zika virus.

PMID- 30226109
TI  - Naturally occurring change in Multiple Sclerosis Walking Scale-12 scores over
      time in multiple sclerosis.
AB  - AIM: This study examined the trajectory and pattern of naturally occurring change
      in perceived walking impairment over a 30-month period in relapsing-remitting
      multiple sclerosis (RRMS). PATIENTS & METHODS: Two hundred and sixty-nine persons
      with RRMS completed the 12-item Multiple Sclerosis Walking Scale (MSWS-12) every
      6 months over a 30-month period. Data were analyzed using latent growth curve
      modeling and latent class growth curve modeling. RESULTS: Latent growth curve
      modeling demonstrated that a linear trajectory adequately described the group
      level pattern of change in MSWS-12 scores over time. Latent class growth curve
      modeling supported a three-class model for describing the heterogeneity of
      changes in MSWS-12 scores over time. CONCLUSION: Walking impairment does change
      over time in RRMS, and this can be described by three patterns of change
      trajectories that differed based on initial status of walking impairment.

PMID- 30226110
TI  - Drug-Induced Sleep Computed Tomography-Directed Upper Airway Surgery for
      Obstructive Sleep Apnea: A Pilot Study.
AB  - Objective A surgical response to upper airway (UA) surgery for obstructive sleep
      apnea (OSA) depends on adequate correction of collapsible sites in the UA. This
      pilot study aimed to examine the surgical response to UA surgery directed by drug
      induced sleep computed tomography (DI-SCT) for OSA. Study Design Prospective case
      series. Setting Tertiary referral center. Subjects and Methods This study
      recruited 29 OSA patients (median age, 41 years; median body mass index, 26.9
      kg/m2) who underwent single-stage DI-SCT-directed UA surgery between October 2012
      and September 2014. DI-SCT was performed with propofol for light sedation with a
      bispectral monitor before and after UA surgery. Nonresponders were defined as
      those with a reduction in apnea-hypopnea index <50% after 6 months following UA
      surgery. Results DI-SCT showed that 28 (97%) patients had collapses at multiple
      sites, all of whom underwent multilevel UA surgery accordingly. The apnea
      hypopnea index decreased from 53.6 to 26.8 ( P < .001). There were 18 (62%)
      nonresponders and 11 (38%) responders. Multiple-site collapses could not predict
      surgical response ( P > .99). The nonresponders had significant improvements in
      velopharyngeal, oropharyngeal lateral wall, and tongue collapses (all P < .05),
      whereas the responders had significant improvements in velopharyngeal and
      oropharyngeal lateral wall collapses (both P <= .05). Conclusion Despite
      multilevel OSA surgery, residual UA obstruction in nonresponders likely occurs
      due to multiple mechanisms. DI-SCT may help to elucidate the reasons for a
      nonresponse.

PMID- 30226111
TI  - The role of optical coherence tomography and infrared oculography in assessing
      the visual pathway and CNS in multiple sclerosis.
AB  - In this review, a current overview is provided of how optical coherence
      tomography and infrared oculography can aid in assessing the visual system and
      CNS in multiple sclerosis (MS). Both afferent and efferent visual disorders are
      common in MS and visual complaints can have a tremendous impact on daily
      functioning. Optical coherence tomography and infrared oculography can detect and
      quantify visual disorders with high accuracy, but could also serve as
      quantitative markers for inflammation, neurodegeneration and network changes
      including cognitive decline in MS patients. The assessment of the efferent and
      afferent visual pathways is relevant for monitoring and predicting the disease
      course, but is also potentially valuable as an outcome measure in therapeutic
      trials.

PMID- 30226112
TI  - A Comparative Effectiveness Trial of Depression Collaborative Care: Subanalysis
      of Comorbid Anxiety.
AB  - The purpose of this exploratory subanalysis was to compare the effects of two
      depression quality improvement approaches on clinical outcomes and service
      utilization for individuals with comorbid depression/anxiety. This study used
      data from Community Partners in Care (CPIC), a cluster-randomized comparative
      effectiveness trial ( N = 1,018; depression = 360; comorbid depression/anxiety =
      658). Each intervention arm received the same quality improvement materials, plus
      either technical support (Resources for Services, RS) or support for
      collaborative implementation planning (Community Engagement and Planning, CEP).
      For the comorbid depression/anxiety subgroup, the collaborative planning arm was
      superior at improving mental health-related quality of life and mental wellness,
      as well as decreasing behavioral hospitalizations and homelessness risk at 6
      months. The effects were not significant at 12 months. A collaborative planning
      process versus technical support for depression quality improvement can have
      short-term effects on mental wellness and social determinants of health among
      those with comorbid depression/anxiety.

PMID- 30226113
TI  - Targeted next-generation sequencing of 50 cancer-related genes in Japanese
      patients with oral squamous cell carcinoma.
AB  - Somatic mutation analysis is a standard of practice for human cancers to identify
      therapeutic sensitization and resistance mutations. We performed a multigene
      sequencing screen to explore mutational hotspots in cancer-related genes using a
      semiconductor-based sequencer. DNA from oral squamous cell carcinoma samples was
      used as a template to amplify 207 regions from 50 cancer-related genes. Of the 80
      oral squamous cell carcinoma specimens from Japanese patients, including formalin
      fixed paraffin-embedded samples, 56 specimens presented at least one somatic
      mutation among the 50 investigated genes, and 17 of these samples showed multiple
      gene somatic mutations. TP53 was the most commonly mutated gene (50.0%), followed
      by CDKN2A (16.3%), PIK3CA (7.5%), HRAS (5.0%), MET (2.5%), and STK11 (2.5%). In
      total, 32 cases (40.0%) were human papillomavirus positive and they were
      significantly less likely to have a TP53, mutation than human papillomavirus
      negative oral squamous cell carcinomas (8/32, 25.0% vs 32/48, 66.7%, p =
      0.00026). We also detected copy number variations, in which segments of the
      genome could be duplicated or deleted from the sequencing data. We detected the
      tumor-specific TP53 mutation in the plasma cell-free DNA from two oral squamous
      cell carcinoma patients, and after surgery, the test for these mutations became
      negative. Our approach facilitates the simultaneous high-throughput detection of
      somatic mutations and copy number variations in oral squamous cell carcinoma
      samples.

PMID- 30226114
TI  - Effect of Pseuderanthemum palatiferum (Nees) Radlk fresh leaf ethanolic extract
      on human breast cancer MDA-MB-231 regulated cell death.
AB  - Leaf extracts of Pseuderanthemum palatiferum (Nees) Radlk were investigated for
      their effects on human breast cancer MDA-MB-231 cell growth inhibition.
      Pseuderanthemum palatiferum (Nees) Radlk extracts were prepared using fresh or
      dried leaves and extracted by either water or 95% ethanol, respectively. Fresh
      leaf ethanolic extract was the most toxic to MDA-MB-231 cells measured by 3-(4,5
      dimethyl)-2,5-diphenyl tetrazolium bromide assay. Fresh leaf ethanolic extract
      treated MDA-MB-231 cell death was stained with propidium iodide and examined
      under fluorescence microscopy. Cell death was confirmed by annexin V-fluorescein
      isothiocyanate/propidium iodide and propidium iodide-stained cells employing flow
      cytometry. The mitochondrial transmembrane potential was disrupted in fresh leaf
      ethanolic extract-treated MDA-MB-231 cells and the percentage of cells with
      reduced mitochondrial transmembrane potential increased according to
      concentrations. Mitochondrial transmembrane potential-driven regulated cell
      deaths were in the form of both apoptosis and necrosis. Oxidative stress probe,
      2',7'-dichlorodihydrofluorescein diacetate, was used to indicate the redox
      status. Dichlorofluorescein level was significantly lower at high fresh leaf
      ethanolic extract concentrations. Total phenolic contents were found in all
      Pseuderanthemum palatiferum (Nees) Radlk extracts, whereas Ca2+ level in the
      cytosol increased, indicating Ca2+ overload and endoplasmic reticulum stress
      involvement with the activation of caspase-3, -8, and -9. In conclusion, fresh
      leaf ethanolic extract induced human breast cancer MDA-MB-231 programmed cell
      death via endoplasmic reticulum and oxidative stress by activating both extrinsic
      and intrinsic signaling pathways.

PMID- 30226115
TI  - Zika virus found in brain tissue of a multiple sclerosis patient undergoing an
      acute disseminated encephalomyelitis-like episode.
AB  - BACKGROUND: A range of different neurological manifestations has been reported in
      fetuses and adults after Zika virus (ZIKV) infection. OBJECTIVE: We describe a
      detection of the ZIKV in the brain tissue from a multiple sclerosis (MS) patient
      with acute disseminated encephalomyelitis (ADEM)-like event in Rio de Janeiro,
      Brazil. METHODS: Biological samples collected during the hospitalization were
      tested by serology and molecular diagnostic for various infectious agents.
      Histopathological analysis was performed using the anti-flavivirus group 4G2
      monoclonal antibody, anti-ZIKV non-structural 1 (NS1) monoclonal antibody, and
      anti-CD4, CD8, and CD11b antibodies. RESULTS: Anti-ZIKV IgM and IgG antibodies
      were positive in the serum and urine. A brain biopsy showed ZIKV protein in brain
      cells and T CD8 infiltration in brain tissue. CONCLUSION: Our data describe the
      coexistence of a recent central nervous system (CNS) ZIKV infection accompanied
      by a severe ADEM-like syndrome outcome in a patient with clinical history of MS.
      A de novo immune response concomitant with ZIKV infection might be involved in
      the mechanism of the ADEM-like syndrome and response to immunotherapy. The
      present report reinforces the importance of providing the differential diagnosis
      of acute episodes of MS exacerbation in an environment prone to ZIKV expression.

PMID- 30226116
TI  - Variability of vestibular aqueduct measurements among axial, single-oblique and
      double-oblique computed tomography images.
AB  - OBJECTIVE: To investigate the morphology and dimensions of the vestibular
      aqueduct on axial, single-oblique and double-oblique computed tomography images.
      METHODS: The computed tomography temporal bone scans of 112 patients were
      retrospectively evaluated. Midpoint and opercular measurements were performed
      using axial, single-oblique and double-oblique images. Morphometric analyses were
      also conducted. The vestibular aqueduct sizes on axial, single-oblique and double
      oblique images were compared. RESULTS: At the midpoint, the mean (+/- standard
      deviation) vestibular aqueduct measured 0.61 +/- 0.23 mm, 0.74 +/- 0.27 mm and
      0.82 +/- 0.38 mm on axial, single-oblique and double-oblique images,
      respectively; at the operculum, the vestibular aqueduct measured 0.91 +/- 0.30
      mm, 1.11 +/- 0.45 mm and 1.66 +/- 1.07 mm on the respective images. The co
      efficients of variation of the vestibular aqueduct measured at the midpoint were
      37.4 per cent, 36.5 per cent and 47.5 per cent on axial, single-oblique and
      double-oblique images, respectively; at the operculum, the measurements were 33.0
      per cent, 40.5 per cent and 64.5 per cent. Regarding morphology, the vestibular
      aqueduct was fissured (33.5 per cent), tubular (64.3 per cent) or invisible (2.2
      per cent). CONCLUSION: The morphology and dimensions of the vestibular aqueduct
      were highly variable among axial, single-oblique and double-oblique images.

PMID- 30226117
TI  - Trajectories of psychiatric diagnoses and medication usage in youth with 22q11.2
      deletion syndrome: a 9-year longitudinal study.
AB  - BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with
      high rates of psychiatric disorders, including schizophrenia in up to 30% of
      individuals with the syndrome. Despite this, we know relatively little about
      trajectories and predictors of persistence of psychiatric disorders from middle
      childhood to early adulthood. Accordingly, we followed youth over four
      timepoints, every 3 years, to assess long-term trajectories of attention-deficit
      hyperactivity disorder (ADHD), anxiety, mood, and psychosis-spectrum disorders
      (PSDs), as well as medication usage. METHODS: Eighty-seven youth with 22q11DS and
      65 controls between the ages of 9 and 15 years at the first timepoint (T1; mean
      age 11.88 +/- 2.1) were followed for 9 years (mean age of 21.22 +/- 2.01 years at
      T4). Baseline cognitive, clinical, and familial predictors of persistence were
      identified for each class of psychiatric disorders. RESULTS: Baseline age and
      parent-rated hyperactivity scores predicted ADHD persistence [area under curve
      (AUC) = 0.81]. The presence of family conflict predicted persistence of anxiety
      disorders (ADs) whereas parent ratings of child internalizing symptoms predicted
      persistence of both anxiety and mood disorders (MDs) (AUC = 0.84 and 0.83,
      respectively). Baseline prodromal symptoms predicted persistent and emergent PSDs
      (AUC = 0.83). Parent-reported use of anti-depressants/anxiolytics increased
      significantly from T1 to T4. CONCLUSIONS: Psychiatric, behavioral, and cognitive
      functioning during late childhood and early adolescence successfully predicted
      children with 22q11DS who were at highest risk for persistent psychiatric illness
      in young adulthood. These findings emphasize the critical importance of early
      assessments and interventions in youth with 22q11DS.

PMID- 30226118
TI  - Eye protection for preventing transmission of respiratory viral infections to
      healthcare workers.

PMID- 30226119
TI  - Antibiotic prescribing for acute respiratory infections in New York City: A model
      for collaboration.
AB  - OBJECTIVE: To assess the status of antibiotic prescribing in the ambulatory
      setting for adult patients with acute respiratory infections (ARIs) and to
      identify opportunities and barriers for outpatient antibiotic stewardship
      programs (ASPs). DESIGN: Mixed methods including point prevalence using chart
      reviews, surveys, and collaborative learning. SETTING: Hospital-owned clinics in
      the New York City area.Participants/PatientsIn total, 31 hospital-owned clinics
      from 9 hospitals and health systems participated in the study to assess ARI
      prescribing practices for patients >18 years old.InterventionsEach clinic
      performed a survey of current stewardship practices, retrospective chart reviews
      of prescribing in 30 randomly selected ARI patients from October 2015 to March
      2016, and surveys of provider characteristics and knowledge. Clinics participated
      in collaborative learning with peers and experts in antibiotic stewardship and
      collected data from June 2016 to August 2016. Sites received data reports by
      individual clinic, aggregated by hospital, and were compared among participating
      clinics. RESULTS: Few sites had outpatient stewardship activities. The
      retrospective review of 1,004 ARI patients revealed that 37.3% of ARI patients
      received antibiotics, with significant variation in prescribing practices among
      sites (17.4%-71.0%; P<.001). Macrolides were the most commonly prescribed
      antibiotics. Most of the 302 respondents recognized the need for tools to assist
      in prescribing. CONCLUSIONS: This collaborative study establishes a baseline
      assessment of the status of outpatient ASPs in New York City. It provides
      hospitals, health systems, and individual clinics with specific data to inform
      their development of stewardship interventions targeting ARIs.

PMID- 30226120
TI  - The British Rhinological Society multidisciplinary consensus recommendations on
      the hospital management of epistaxis - ERRATUM.

PMID- 30226121
TI  - Prescribers' knowledge, attitudes and perceptions about blood culturing practices
      for adult hospitalized patients: a call for action.

PMID- 30226123
TI  - QUALITY AND USE OF FREE SMOKING CESSATION APPS FOR SMARTPHONES.
AB  - OBJECTIVES: Smartphone Apps are one of the tools available to support patients
      who wish to quit smoking. Content analysis studies have indicated multiple
      deficiencies within these Apps including minimal use of evidence-based research
      and Nicotine Dependence Treatment Provider (NDTP) in App development. The aim of
      this study was to determine quality and features of smoking cessation Apps
      available on Android(r) and iOS(r) platforms. METHODS: The first fifty free
      smoking cessation Apps available for download using the search term smoking
      cessation on Google Play Store and Apple App Store were chosen. Each of these
      Apps was analyzed and categorized based on ratings, target audience age,
      language, and a variety of tracking functionalities noted on the Apps.
      Indications and suggestions regarding either the use of NDTP or evidence-based
      behavior change protocols were noted. RESULTS: There were no significant
      differences in the features of smoking cessation Apps on Android and iOS. Only 15
      percent of all Apps analyzed on both platforms indicated some involvement of NDTP
      and there was no difference between the two platforms. More than 50 percent of
      Apps studied were downloaded over half a million times and the average user
      rating was 3.89/5.00 for Android and 3.72/5.00 for iOS with no significant
      difference. CONCLUSIONS: Most smoking cessation Apps in both platforms offer
      basic tracking functionalities with limited motivational tips. Only a handful of
      Apps have moved beyond this role and while their development is applaudable much
      innovation remains.

PMID- 30226122
TI  - Epidemiology and risk factors for recurrent Staphylococcus aureus colonization
      following active surveillance and decolonization in the NICU.
AB  - OBJECTIVES: To examine neonatal risk factors associated with recurrent
      Staphylococcus aureus colonization and to determine the genetic relatedness of S.
      aureus strains cultured from neonates before and after decolonization.Study
      designSingle-center retrospective cohort study of neonates admitted to the
      neonatal intensive care unit (NICU) from April 2013 to December 2015, during
      which weekly nasal cultures from hospitalized NICU patients were routinely
      obtained for S. aureus surveillance. SETTING: Johns Hopkins Hospital's 45-bed
      level IV NICU in Baltimore, Maryland. METHODS: Demographics and clinical data
      were collected on all neonates admitted to the NICU with S. aureus nasal
      colonization who underwent mupirocin-based decolonization during the study
      period. A decolonized neonate was defined as a neonate with >=1 negative culture
      after intranasal mupirocin treatment. Pulsed-field gel electrophoresis was used
      for strain typing. RESULTS: Of 2,060 infants screened for S. aureus, 271 (13%)
      were colonized, and 203 of these 271 (75%) received intranasal mupirocin. Of
      those treated, 162 (80%) had follow-up surveillance cultures, and 63 of these 162
      infants (39%) developed recurrent colonization after treatment. The S. aureus
      strains were often genetically similar before and after decolonization. The
      presence of an endotracheal tube or nasal cannula/mask was associated with an
      increased risk of recurrent S. aureus colonization (hazard ratio [HR], 2.65; 95%
      confidence interval [CI], 1.19-5.90; and HR, 2.21; 95% CI, 1.02-4.75,
      respectively). CONCLUSION: Strains identified before and after decolonization
      were often genetically similar, and the presence of invasive respiratory devices
      increased the risk of recurrent S. aureus nasal colonization in neonates. To
      improve decolonization efficacy, alternative strategies may be needed.

PMID- 30226124
TI  - Effectiveness of ultraviolet disinfection in reducing hospital-acquired
      Clostridium difficile and vancomycin-resistant Enterococcus on a bone marrow
      transplant unit.
AB  - OBJECTIVE: To determine the effectiveness of ultraviolet (UV) environmental
      disinfection system on rates of hospital-acquired vancomycin-resistant
      enterococcus (VRE) and Clostridium difficile. DESIGN: Using active surveillance
      and an interrupted time-series design, hospital-acquired acquisition of VRE and
      C. difficile on a bone marrow transplant (BMT) unit were examined before and
      after implementation of terminal disinfection with UV on all rooms regardless of
      isolation status of patients. The main outcomes were hospital-based acquisition
      measured through (1) active surveillance: admission, weekly, and discharge
      screening for VRE and toxigenic C. difficile (TCD) and (2) clinical surveillance:
      incidence of VRE and CDI on the unit. SETTING: Bone marrow transplant unit at a
      tertiary-care cancer center.ParticipantsStem cell transplant (SCT)
      recipients.InterventionTerminal disinfection of all rooms with UV regardless of
      isolation status of patients. RESULTS: During the 20-month study period, 579
      patients had 704 admissions to the BMT unit, and 2,160 surveillance tests were
      performed. No change in level or trend in the incidence of VRE (trend incidence
      rate ratio [IRR], 0.96; 95% confidence interval [CI], 0.81-1.14; level IRR, 1.34;
      95% CI, 0.37-1.18) or C. difficile (trend IRR, 1.08; 95% CI, 0.89-1.31; level
      IRR, 0.51; 95% CI, 0.13-2.11) was observed after the intervention. CONCLUSIONS:
      Utilization of UV disinfection to supplement routine terminal cleaning of rooms
      was not effective in reducing hospital-acquired VRE and C. difficile among SCT
      recipients.

PMID- 30226125
TI  - Comparison of cognitive functions between first-episode schizophrenia patients,
      their unaffected siblings and individuals at clinical high-risk for psychosis.
AB  - BACKGROUND: Cognitive impairment is a core feature of schizophrenia and has been
      observed in both familial (FHR) and clinical high-risk (CHR) samples.
      Nonetheless, there is a paucity of research directly contrasting cognitive
      profiles in these two high-risk states and first-episode schizophrenia. This
      study aimed to compare cognitive functions in patients with first-episode
      schizophrenia-spectrum disorder (FES), their unaffected siblings (FHR), CHR
      individuals and healthy controls. METHOD: A standardized battery of cognitive
      assessments was administered to 69 FES patients, 71 help-seeking CHR individuals
      without family history of psychotic disorder, 50 FHR participants and 68
      controls. FES and CHR participants were recruited from territory-wide early
      intervention service for psychosis in Hong Kong. CHR status was ascertained using
      Comprehensive Assessment of At-Risk Mental State. RESULTS: Among four groups, FES
      patients displayed the largest global cognitive impairment and had medium-to
      large deficits across all cognitive tests relative to controls. CHR and FHR
      participants significantly underperformed in most cognitive tests than controls.
      Among various cognitive tests, digit symbol coding demonstrated the greatest
      magnitude of impairment in FES and CHR groups compared with controls. No
      significant difference between two high-risk groups was observed in global
      cognition and all individual cognitive tests except digit symbol coding which
      showed greater deficits in CHR than in FHR participants. CONCLUSION: Clinical and
      familial risk groups experienced largely comparable cognitive impairment that was
      intermediate between FES and controls. Digit symbol coding may have the greatest
      discriminant capacity in distinguishing FES and CHR from healthy controls, and
      between two high-risk samples.

PMID- 30226126
TI  - Clostridium difficile colonization among patients with clinically significant
      diarrhea and no identifiable cause of diarrhea.
AB  - OBJECTIVE: To determine the prevalence of Clostridium difficile colonization
      among patients who meet the 2017 IDSA/SHEA C. difficile infection (CDI) Clinical
      Guideline Update criteria for the preferred patient population for C. difficile
      testing. DESIGN: Retrospective cohort. SETTING: Tertiary-care hospital in St.
      Louis, Missouri.PatientsPatients whose diarrheal stool samples were submitted to
      the hospital's clinical microbiology laboratory for C. difficile testing (toxin
      EIA) from August 2014 to September 2016.InterventionsElectronic and manual chart
      review were used to determine whether patients tested for C. difficile toxin had
      clinically significant diarrhea and/or any alternate cause for diarrhea.
      Toxigenic C. difficile culture was performed on all stool specimens from patients
      with clinically significant diarrhea and no known alternate cause for their
      diarrhea. RESULTS: A total of 8,931 patients with stool specimens submitted were
      evaluated: 570 stool specimens were EIA positive (+) and 8,361 stool specimens
      were EIA negative (-). Among the EIA+stool specimens, 107 (19% of total) were
      deemed eligible for culture. Among the EIA- stool specimens, 515 (6%) were
      eligible for culture. One EIA+stool specimen (1%) was toxigenic culture negative.
      Among the EIA- stool specimens that underwent culture, toxigenic C. difficile was
      isolated from 63 (12%). CONCLUSIONS: Most patients tested for C. difficile do not
      have clinically significant diarrhea and/or potential alternate causes for
      diarrhea. The prevalence of toxigenic C. difficile colonization among EIA-
      patients who met the IDSA/SHEA CDI guideline criteria for preferred patient
      population for C. difficile testing was 12%.

PMID- 30226127
TI  - Supporting the bereaved in greatest need: We can do better.

PMID- 30226128
TI  - Prolonged antimicrobial prophylaxis following cardiac device procedures increases
      preventable harm: insights from the VA CART program.
AB  - BACKGROUND: The rate of cardiovascular implantable electronic device (CIED)
      infection is increasing coincident with an increase in the number of device
      procedures. Preprocedural antimicrobial prophylaxis reduces CIED infections;
      however, there is no evidence that prolonged postprocedural antimicrobials
      additionally reduce risk. Thus, we sought to quantify the harms associated with
      this approach. OBJECTIVE: To measure the association between Clostridium
      difficile infection (CDI), acute kidney injury (AKI) and receipt of prolonged
      postprocedural antimicrobials. METHODS: CIED procedures entered into the VA
      Clinical Assessment Reporting and Tracking Electrophysiology (CART-EP) database
      during fiscal years 2008-2016 were included. The primary outcome was 90-day
      incidence of CDI and the secondary outcome was the 7-day incidence of AKI. The
      primary exposure measure was duration of postprocedural antimicrobial therapy.
      Associations were measured using Cox-proportional hazards and binomial
      regression. RESULTS: Prolonged postprocedural antimicrobial therapy was
      identified following 3,331 of 6,497 CIED procedures (51.3%), and the median
      duration of prophylaxis was 5 days. Prolonged postprocedural antimicrobial use
      was associated with increased risk of CDI (hazard ratio [HR], 2.90; 95%
      confidence interval [CI], 1.54-5.46). Of the 27 patients who developed CDI, 11
      subsequently died. Postprocedural antimicrobial use with >=2 antimicrobials was
      associated with an increased risk of AKI (OR, 4.16; 95% CI, 2.50-6.90). The
      impact was particularly significant when one of the dual agents prescribed was
      vancomycin (adjusted OR, 8.41; 95% CI, 5.53-12.79). CONCLUSIONS: Prolonged
      antimicrobial prophylaxis following CIED procedures increases preventable harm;
      this practice should be discouraged in procedural settings such as the cardiac
      electrophysiology laboratory.

PMID- 30226129
TI  - Transfer of pathogens to and from patients, healthcare providers and medical
      devices during care activity - a systematic review and meta-analysis-CORRIGENDUM.

PMID- 30226130
TI  - Highly Accurate Chimeric Proteins for the Serological Diagnosis of Chronic Chagas
      Disease: A Latent Class Analysis.
AB  - The existence of an imperfect reference standard presents complications when
      evaluating the unbiased performance of novel diagnostic techniques. This is
      especially true in the absence of a gold standard, as is the case in chronic
      Chagas disease (CD) diagnosis. To circumvent this constraint, we elected to use
      latent class analysis (LCA). Previously, our group demonstrated the high
      performance of four Trypanosoma cruzi-chimeric proteins (Molecular Biology
      Institute of Parana [IBMP]-8.1, -8.2, -8.3, and -8.4) for CD diagnosis using
      several distinct immunoassays. Although commercial tests had previously been
      established as a reference standard, the diagnostic performance of these chimeric
      antigens could present bias because these tests fail to produce 100% accurate
      results. Thus, we used LCA to assess the performance of these IBMP chimeric
      antigens in chronic CD diagnosis. Using the LCA model as a gold standard,
      sensitivity and specificity values ranged from 93.5% to 99.4% and 99.6% to 100%,
      respectively. The accuracy values were 96.2% for IBMP-8.2, approximately 98% for
      IBMP-8.1 and IBMP-8.3, and nearly 100% for IBMP-8.4. For IBMP-8.1 and IBMP-8.2,
      higher positive predictive values were associated with increases in hypothetical
      prevalence. Similarly, higher hypothetical prevalence resulted in lower negative
      predictive values for IBMP-8.1, IBMP-8.2, and IBMP-8.3. In addition, samples with
      serodiscordant results from commercial serological tests were analyzed using LCA.
      Molecular Biology Institute of Parana -8.1 demonstrated potential for use in
      confirmatory testing with regard to samples with inconsistent results. Moreover,
      our findings further confirmed the remarkable performance of the IBMP-8.4 antigen
      to diagnose chronic CD in both endemic and non-endemic areas.

PMID- 30226132
TI  - Development and Evaluation of a Multiplex Quantitative Real-Time Polymerase Chain
      Reaction for Hookworm Species in Human Stool.
AB  - Hookworm disease caused by Necator americanus, Ancylostoma duodenale, and
      Ancylostoma ceylanicum affects half a billion people worldwide. The prevalence
      and intensity of infection of individual hookworm species are vital for assessing
      morbidity and generating targeted intervention programs for their control. The
      present study aims to evaluate a multiplex real-time quantitative PCR (qPCR)
      assay to determine the prevalence and egg intensity of all three hookworm species
      and compare this with standard microscopy and published genus-based conventional
      and real-time multiplex qPCRs. Performance of the diagnostic assays was evaluated
      using DNA extracted from 192 fecal samples collected as part of a soil
      transmitted helminth (STH) survey in northern Cambodia. The prevalence of
      hookworms as detected by the multiplex hookworm qPCR of 84/192 (43.8%) was
      significantly higher than that using microscopy of 49/192 (25.5%). The hookworm
      multiplex qPCR showed very good agreement for the detection of both N. americanus
      (Kappa 0.943) and Ancylostoma spp. (Kappa 0.936) with a multiplex STH qPCR. A
      strong and moderate quantitative correlation between cycle threshold and eggs per
      gram (EPG) feces was obtained for the hookworm qPCR for seeded DNA egg extracts
      (R 2 >= 0.9004) and naturally egg-infected individuals (R 2 = 0.6848),
      respectively. The newly developed hookworm quantitative multiplex qPCR has the
      potential for application in anthelmintic efficacy trials and for monitoring the
      success of mass deworming programs targeting individual species of anthroponotic
      and zoonotic hookworms.

PMID- 30226131
TI  - Influenza-Like Illness in Travelers to the Developing World.
AB  - Travelers to developing regions are at risk for development of influenza-like
      illness (ILI). Little is known of traveler and trip characteristics associated
      with the development of ILI. TravMil is a prospective observational study,
      enrolling subjects presenting to six military travel clinics or predeployment
      screening sites. We analyzed pre- and post-travel surveys from travelers visiting
      regions outside of the continental United States, Western or Northern Europe,
      Canada, Australia, or New Zealand between January 2010 and March 2016. Influenza
      like illness was defined as a self-reported fever associated with either sore
      throat or cough. Trip and traveler characteristics were analyzed to determine
      risk factors for the development of ILI. Two thousand nine hundred and thirty-two
      trips were recorded (55% male, median age 45 years, 69% white, 51% on vacation,
      median travel duration 17 days). The 2,337 trips included the number of self
      reported influenza vaccinations in the preceding 5 years (median 5). Eleven
      percent of the trips were complicated by an ILI lasting a median of 5 days; 70%
      and 17% of these reported upper and lower respiratory tract infection,
      respectively, and 12% reported both. On multivariate analysis, increased risk of
      ILI was associated with female gender (odds ratio [OR]: 1.60 [confidence interval
      (CI): 1.25-2.05], P < 0.01), age (years) (OR: 1.01 [CI: 1.01-1.02], P < 0.01);
      and duration of travel (days) (OR: 1.01 [CI: 1.00-1.01], P < 0.01). Influenza
      like illness is common in travelers, regardless of traveler characteristics,
      purpose of travel, destination, or season of year. Female gender, older age, and
      longer duration of travel were associated with an increased risk of ILI.
      Additional tools and strategies are needed to prevent ILI in international
      travelers.

PMID- 30226133
TI  - Management and Follow-up Practices of Children with Unclassified Fever in Rural
      Ethiopia: Experiences of Health Extension Workers and Caregivers.
AB  - Different health-care management guidelines by the World Health Organization
      exist to help health workers in resource-limited settings treat patients.
      However, for children with unclassified fever and no danger signs, management
      guidelines are less clear and follow-up recommendations differ. Both a "universal
      follow-up" for all children, irrespective of health status, and a "conditional
      follow-up" only for children whose fever persists are recommended in different
      guidelines. It is unclear how feasible and acceptable these two different follow
      up guidelines are among community health workers and caregivers of the sick
      child. This qualitative study was conducted in Ethiopia and was nested within a
      cluster-randomized controlled trial (cRCT). It aimed to determine health
      extension workers' (HEWs') and caregivers' experiences of the management of
      febrile children and their perceptions of universal versus conditional follow-up
      recommendations. Seventeen HEWs and 20 caregivers were interviewed. The
      interviews revealed that HEWs' understanding of how to handle an unclassified
      fever diagnosis increased with the implementation of the cRCT in both study arms
      (universal versus conditional follow-up). This enabled HEWs to withhold medicines
      from children with this condition and avoid referral to health centers. Both
      follow-up recommendations had perceived advantages, while the universal follow-up
      provided an opportunity to see the child's health progress, the conditional
      follow-up advice allowed saving time and costs. The findings suggest that
      improved awareness of the unclassified fever condition can make HEWs feel more
      comfortable in managing these febrile children themselves and omitting
      unnecessary medication. Future community-level management guidelines should
      provide clearer instructions on managing fever where no malaria, pneumonia,
      diarrhea, or danger signs are present.

PMID- 30226134
TI  - Predicting Mortality for Adolescent and Adult Patients with Fever in Resource
      Limited Settings.
AB  - Febrile illnesses are a major cause of mortality in sub-Saharan Africa. Early
      identification of patients at increased risk of death may avert adverse outcomes.
      We aimed to independently evaluate the performance of the Modified Early Warning
      Score, quick Sequential Organ Failure Assessment (qSOFA) score, and Integrated
      Management of Adolescent and Adult Illness (IMAI) emergency signs and severity
      criteria to predict in-hospital mortality among a prospective cohort of febrile
      patients in Tanzania. We evaluated 419 patients aged >= 10 years in the period
      2007-2008. Of the 44 patients who died, 31 (70.5%) were human immunodeficiency
      virus (HIV) infected. On univariate analysis, in-hospital mortality was
      associated with HIV infection, oxygen saturation < 90%, respiratory distress,
      Glasgow Coma Scale < 15, neck stiffness, unconsciousness, convulsions, hemoglobin
      < 9 g/dL, absence of a systemic syndrome, and neurologic syndrome. A qSOFA score
      >= 2, the presence of at least one, two, or three IMAI emergency signs, and IMAI
      severe respiratory distress syndrome without shock were significantly associated
      with in-hospital mortality. The criterion "presence of at least one IMAI
      emergency sign" showed a good diagnostic accuracy, as highlighted by the high
      sensitivity, low negative likelihood ratio, and wide area under the receiver
      operating characteristics curve. The remaining scores showed a poor performance
      in predicting fatal outcomes in our study population. Further studies are needed
      to validate our findings and to derive early warning scores that have good
      clinical performance in settings throughout sub-Saharan Africa.

PMID- 30226135
TI  - Trends in C-Reactive Protein, D-Dimer, and Fibrinogen during Therapy for HIV
      Associated Multidrug-Resistant Tuberculosis.
AB  - HIV-positive adults on treatment for multi drug-resistant tuberculosis (MDR-TB)
      experience high mortality. Biomarkers of HIV/MDR-TB treatment response may enable
      earlier treatment modifications that improve outcomes. To determine whether
      changes in C-reactive protein (CRP), D-dimer, and fibrinogen were associated with
      treatment outcome among those with HIV/MDR-TB coinfection, we studied 20 HIV
      positive participants for the first 16 weeks of MDR-TB therapy. Serum CRP,
      fibrinogen, and D-dimer were measured at baseline and serially while on
      treatment. At baseline, all biomarkers were elevated above normal levels, with
      median CRP 86.15 mg/L (interquartile range [IQR] 29.25-149.32), D-dimer 0.85
      ug/mL (IQR 0.34-1.80), and fibrinogen 4.11 g/L (IQR 3.75-6.31). C-reactive
      protein decreased significantly within 10 days of treatment initiation and
      fibrinogen within 28 days; D-dimer did not change significantly. Five (25%)
      participants died after a median of 32 days. Older age (median age of 38y among
      survivors and 54y among deceased, P = 0.008) and higher baseline fibrinogen (3.86
      g/L among survivors and 6.37 g/L among deceased, P = 0.02) were significantly
      associated with death. After adjusting for other measured variables, higher CRP
      concentrations at the beginning of each measurement interval were significantly
      associated with a higher risk of death during that interval. Trends in fibrinogen
      and CRP may be useful for evaluating early response to treatment among
      individuals with HIV/MDR-TB coinfection.

PMID- 30226136
TI  - Socioeconomic Factors Associated with Fasciola hepatica Infection Among Children
      from 26 Communities of the Cusco Region of Peru.
AB  - Fasciola hepatica is the most widely distributed trematode-affecting humans. The
      Andes Mountains are highly endemic for fascioliasis. We report results of a cross
      sectional study evaluating the epidemiology of Fasciola among children in 26
      agricultural communities in the Cusco region of Peru. Children 3 to 16 years old
      were enrolled in preschools and schools. Blood from participants was tested for
      complete blood counts, transaminases, and Fasciola antibodies. Stool samples were
      tested for Fasciola and other parasites. A total of 2,515 children were included
      in the analysis and the mean age was 9.6 years (+/-3.6). Ten percent (253) of the
      children had at least one positive test for Fasciola, 6% had chronic infection,
      and 0.4% acute infection. The rest of the subjects had only antibodies against
      Fasciola. The prevalence of infection varied from 0% to 20% between communities.
      Children with evidence of Fasciola exposure were older, lived at higher
      altitudes, and had a lower socioeconomic status than children without infection.
      The logistic regression analysis showed that children from Ancahuasi district,
      older children, and children with higher measures of poverty were more likely to
      have Fasciola exposure. Fascioliasis is common in the Cusco region and associated
      with poverty. However, the distribution varies markedly between communities.

PMID- 30226138
TI  - Baseline Characterization of Dengue Epidemiology in Yogyakarta City, Indonesia,
      before a Randomized Controlled Trial of Wolbachia for Arboviral Disease Control.
AB  - Dengue is endemic in Indonesia. Here, we describe the epidemiology of dengue in
      the city of Yogyakarta, Central Java, as a prelude to implementation of a cluster
      randomized trial of Wolbachia for the biocontrol of arboviral transmission.
      Surveillance records from 2006 to 2016 demonstrate seasonal oscillations of
      dengue incidence with varying magnitude. Two lines of evidence demonstrate a high
      force of infection; the hospitalized case burden of patients diagnosed with
      dengue hemorrhagic fever or dengue shock syndrome over the last decade consisted
      predominantly of children/adolescents, and a serosurvey of 314 healthy children
      aged 1-10 years found 68% possessed dengue virus-neutralizing antibodies.
      Finally, a mobility survey indicated children aged 1-10 years, and particularly 1
      5 year-olds, spent most of their daytime hours at home. These findings inform the
      design of clinical trials to measure the impact of novel vector control methods
      such as Wolbachia introgression into Aedes aegypti mosquitoes, by providing
      baseline data on disease incidence and identifying subpopulations for recruitment
      into prospective studies of dengue virus infection and disease. The mobility
      survey findings indicate that in cluster trials of interventions applied at the
      community level, young children can reasonably be expected to spend most of their
      exposure time, in epidemiological terms, within the treatment arm to which they
      were randomized.

PMID- 30226137
TI  - Seroepidemiology of Burkholderia pseudomallei, Etiologic Agent of Melioidosis, in
      the Ouest and Sud-Est Departments of Haiti.
AB  - Burkholderia pseudomallei, the etiological agent of melioidosis, has been
      hypothesized to be endemic throughout the Caribbean, including the impoverished
      nation of Haiti. However, because of the protean clinical manifestations,
      presence of asymptomatic infections, and limited medical diagnostic capacity, the
      identification of active melioidosis cases remains challenging. A
      seroepidemiological study was conducted using a novel enzyme-linked immunosorbent
      assay (ELISA) to detect antibodies toward B. pseudomallei in the native
      population. The performance of an indirect ELISA with purified lipopolysaccharide
      (LPS) from B. pseudomallei was evaluated using serum collected from rhesus
      macaques exposed to aerosolized B. pseudomallei. After optimization, serum
      collected from asymptomatic population members (n = 756) was screened for
      polyvalent (immunoglobulin M [IgM]/ immunoglobulin G [IgG]/ immunoglobulin A) and
      monoclonal (IgG or IgM) immunoglobulins against B. pseudomallei LPS. The
      population seroprevalence was 11.5% (95% confidence interval [CI]: 9.2, 13.8) for
      polyvalent immunoglobulins, 9.8% (95% CI: 7.7, 11.9) for IgG, and 1.7% (95% CI:
      0.8, 2.6%) for IgM. The seroprevalence was not significantly different by gender
      (P = 0.16), but increased significantly (P < 0.001) with age, yielding an
      estimated annual seroconversion rate of 1.05% (95% CI: 0.81, 1.3). The detection
      of both recent (IgM+) and previous (IgG+) exposure to B. pseudomallei provides
      serological evidence that melioidosis is endemic in Haiti.

PMID- 30226139
TI  - A Collaborative Multidisciplinary and Without-Walls Research Curriculum in Global
      Health.
AB  - Longitudinal and collaborative global health research curricula to train a well
      versed global health corps through skills building in assessment and evaluation
      are lacking. A without-walls research curriculum was offered to medical and
      public health students between 2007 and 2015. Mentored cross-disciplinary
      research projects were developed and implemented in partnership with communities.
      A multilevel mixed methods design, including semi-structured interviews, post
      curriculum surveys, presentations, publications, postgraduation metrics, and
      feedback from project sites, evaluated educational outcomes. Students (N = 25;
      aged 27 +/- 1.9 years; 90.5% female) participated in the studies in 12 countries,
      resulting in 26 national-level presentations and 24 peer-reviewed publications,
      including per student average and range of Institutional Review Board submission
      (0.95; 0-3), poster presentation (0.85; 0-3), oral presentation (0.65; 0-2), and
      peer-reviewed submission (1.05; 0-4). On average, the studies (40% mixed methods)
      lasted 2 years. Analyses and manuscript writing were the most challenging; data
      collection and presentations were the most rewarding. Majority of the
      participants strongly agreed with achieving skills in community engagement,
      interviewing techniques, research design and implementation, research
      dissemination, and career development. Interview themes included expectations and
      learning goals, effective mentorship, impact on career goals, and ethical
      learning. Mentorship qualities were accessibility, real-time problem solving,
      research expertise, advocate, and balancing guidance with independence. Project
      sites' feedback was overwhelmingly positive regarding the projects' impact.
      Postgraduation participants hold positions in humanitarian organizations,
      research programs serving the underserved, and primary care residencies,
      fellowships, and faculty. This experience illustrates the feasibility and
      effectiveness of mentored global health research and underlines the crucial link
      between community collaboration and scholarship for effective global health
      practice.

PMID- 30226140
TI  - Correlates of Late Presentation to HIV care in a South Indian Cohort.
AB  - Late presentation to healthcare by HIV infected patients' is common in India
      despite access to free combination antiretroviral therapy (cART). We assessed
      risk factors for late presentation among patients with a recent HIV diagnosis in
      an academic university-based antiretroviral treatment center. This retrospective
      study included 474 recently diagnosed HIV-infected patients registered for cART
      between 2012 and 2013. Subjects with CD4+ T-lymphocyte (CD4) count <= 350
      cells/MUL or with an AIDS defining event were defined as late presenters (LP) and
      patients with CD4 count <= 200 cells/MUL or with an AIDS defining event were
      defined as LP with advanced HIV disease (LPAD). Multivariable logistic regression
      analysis was used to investigate factors associated with late presentation. Of
      the 474 patients, 356 (75.1%) were LP. Of these, 299 (83.99%) were LPAD and 57
      (16.01%) LP were AIDS-free. Median CD4 count among LP was 134 cells/MUL
      (interquartile range 72.25-219). Mean age of LP was 42.50 +/- 8.88 years; 256
      (71.9%) were males. Increasing age (> 51 years; Adjusted odds ratio [aOR] 4.19; P
      = 0.014) and rural residence (aOR 3.19; P = < 0.001) were independently
      associated with late presentation. HIV-positive housewives (aOR 0.34; P = 0.027),
      HIV-positive individuals with negative partners (aOR 0.48; P = 0.006), and
      partners with unknown HIV status (aOR 0.43; P = 0.007) were less likely to
      present late compared with positive partners of people living with HIV/AIDS
      (PLWHA). Most patients were LP despite free access to cART. Rural population and
      older PLWHA should be targeted while implementing HIV care. There is a need to
      strengthen the HIV care cascade by linking PLWHA to cART immediately after
      diagnosis.

PMID- 30226141
TI  - Surveillance for Flaviviruses Near the Mexico-U.S. Border: Co-circulation of
      Dengue Virus Serotypes 1, 2, and 3 and West Nile Virus in Tamaulipas, Northern
      Mexico, 2014-2016.
AB  - A clinical, serological, and molecular investigation was performed to determine
      the presence of dengue virus (DENV) and other flaviviruses among residents of the
      city of Reynosa, Tamaulipas, on the Mexico-U.S. border in 2014-2016. The sample
      population consisted of 2,355 patients with suspected dengue, in addition to 346
      asymptomatic individuals recruited during a household-based epidemiological
      investigation designed to identify flavivirus seroconversions. Sera were
      collected from patients with suspected dengue in the acute phase of illness and
      from asymptomatic individuals at enrollment and every 5-7 months for 19 months.
      Sera from suspected dengue patients were tested for DENV antigen by enzyme-linked
      immunosorbent assay (ELISA), and select antigen-positive sera were further tested
      using a serotype-specific, quantitative reverse transcription-polymerase chain
      reaction. Sera from the household cohort were tested for flavivirus-reactive
      antibodies by immunoglobulin (Ig) M and IgG ELISAs using DENV antigen. A total of
      418 (17.7%) patients with suspected dengue had laboratory-confirmed DENV
      infections, including 82 patients who were positive for DENV RNA. The most
      frequently detected serotype was DENV-1 (61 patients), followed by DENV-2 (16
      patients) and DENV-3 (five patients). A total of 217 (62.7%) asymptomatic
      individuals had flavivirus-reactive antibodies at enrollment, and nine flavivirus
      naive individuals seroconverted. Sera from a subset of dengue patients and
      household participants, including all those who seroconverted, were further
      tested by plaque reduction neutralization test, resulting in the detection of
      antibodies to DENV-1, DENV-2, and West Nile virus. In summary, we provide
      evidence for the co-circulation of multiple flaviviruses in Reynosa, Tamaulipas,
      on the Mexico-U.S. border.

PMID- 30226142
TI  - Case Report: Ivermectin and Albendazole Plasma Concentrations in a Patient with
      Disseminated Strongyloidiasis on Extracorporeal Membrane Oxygenation and
      Continuous Renal Replacement Therapy.
AB  - Disseminated strongyloidiasis is often fatal, despite treatment with oral
      albendazole and parenteral ivermectin (IVM). Here, we report elevated plasma IVM
      and albendazole sulfoxide concentrations in the context of extracorporeal
      membrane oxygenation and continuous renal replacement therapy in a patient with
      disseminated strongyloidiasis treated with subcutaneous IVM and nasogastric
      albenzadole. Despite elevated drug plasma concentrations, live filariform larvae
      were detected in endotracheal aspirates after 2 weeks of treatment.

PMID- 30226143
TI  - Seroprevalence and Symptomatic Attack Rate of Chikungunya Virus Infection, United
      States Virgin Islands, 2014-2015.
AB  - When introduced into a naive population, chikungunya virus generally spreads
      rapidly, causing large outbreaks of fever and severe polyarthralgia. We randomly
      selected households in the U.S. Virgin Islands (USVI) to estimate seroprevalence
      and symptomatic attack rate for chikungunya virus infection at approximately 1
      year following the introduction of the virus. Eligible household members were
      administered a questionnaire and tested for chikungunya virus antibodies.
      Estimated proportions were calibrated to age and gender of the population. We
      enrolled 509 participants. The weighted infection rate was 31% (95% confidence
      interval [CI]: 26-36%). Among those with evidence of chikungunya virus infection,
      72% (95% CI: 65-80%) reported symptomatic illness and 31% (95% CI: 23-38%)
      reported joint pain at least once per week approximately 1 year following the
      introduction of the virus to USVI. Comparing rates from infected and noninfected
      study participants, 70% (95% CI: 62-79%) of fever and polyarthralgia and 23% (95%
      CI: 9-37%) of continuing joint pain in patients infected with chikungunya virus
      were due to their infection. Overall, an estimated 43% (95% CI: 33-52%) of the
      febrile illness and polyarthralgia in the USVI population during the outbreak was
      attributable to chikungunya virus and only 12% (95% CI: 7-17%) of longer term
      joint pains were attributed to chikungunya virus. Although the rates of
      infection, symptomatic disease, and longer term joint symptoms identified in USVI
      are similar to other outbreaks of the disease, a lower proportion of acute fever
      and joint pain was found to be attributable to chikungunya virus.

PMID- 30226144
TI  - Molecular Detection of Bartonella bacilliformis in Lutzomyia maranonensis in
      Cajamarca, Peru: A New Potential Vector of Carrion's Disease in Peru?
AB  - Carrion's disease is a neglected, vector-borne illness that affects Colombia,
      Ecuador, and especially Peru. The phlebotomine sand flies Lutzomyia verrucarum
      and Lutzomyia peruensis are the main illness vectors described, although other
      species may be implicated in endemic areas such as some northern Peruvian
      regions, in which Carrion's disease vector has not been established. The aim of
      this study was to evaluate the presence of Bartonella bacilliformis DNA in
      Lutzomyia maranonensis from Cajamarca, northern Peru. This sand fly has not been
      defined as a vector yet. Centers for Disease Control and Prevention light traps
      were used to collect adult phlebotomine sand flies from 2007 to 2008 in the
      Cajamarca department. Female specimens were identified using morphological keys
      and were grouped into pools of five sand flies, taking into account district and
      sampling site (intradomicile or peridomicile). DNA was extracted, and then
      conventional and real-time polymerase chain reaction (RT-PCR) were performed to
      detect B. bacilliformis and subsequently confirmed by sequencing. A total of 383
      specimens of L. maranonensis species were analyzed. Two of 76 pools were positive
      for B. bacilliformis by sequencing; all positives pools were from Querocotillo
      district. In addition, Mesorhizobium spp. were identified in two pools of sand
      flies, which is an alpha-proteobacteria phylogenetically very close to B.
      bacilliformis. This study presents molecular evidence that suggests L.
      maranonensis is naturally infected by B. bacilliformis in the Cajamarca
      department. Further research should determine if L. maranonensis is a vector and
      could transmit B. bacilliformis.

PMID- 30226145
TI  - Gametocyte Carriage, Antimalarial Use, and Drug Resistance in Cambodia, 2008
      2014.
AB  - Gametocytes are the malaria parasite stages responsible for transmission from
      humans to mosquitoes. Gametocytemia often follows drug treatment, especially as
      therapies start to fail. We examined Plasmodium falciparum gametocyte carriage
      and drug resistance profiles among 824 persons with uncomplicated malaria in
      Cambodia to determine whether prevalent drug resistance and antimalarial use has
      led to a concentration of drug-resistant parasites among gametocyte carriers.
      Although report of prior antimalarial use increased from 2008 to 2014, the
      prevalence of study participants presenting with microscopic gametocyte carriage
      declined. Gametocytemia was more common in those reporting antimalarial use
      within the past year, and prior antimalarial use was correlated with higher IC50s
      to piperaquine and mefloquine, as well as to increased pfmdr1 copy number.
      However, there was no association between microscopic gametocyte carriage and
      parasite drug resistance. Thus, we found no evidence that the infectious
      reservoir, marked by those carrying gametocytes, is enriched with drug-resistant
      parasites.

PMID- 30226146
TI  - Socially Awkward Abroad: A Call for Social Media Policies in Residencies that
      Offer Global Health Electives.
AB  - Both social media use and the popularity of global health electives (GHEs) have
      increased in recent years. Social media use during GHE is commonplace and has
      benefits, yet sharers may not consider the ramifications of these posts,
      including privacy violations. Social media policies-which have become more common
      in residency programs-may aid in providing clear expectations to trainees abroad.
      The authors aimed to determine the prevalence of social media policies among
      pediatric residency programs that offer GHE. The authors used a cross-sectional
      survey design in which educators at pediatric residency programs that offer GHE
      were surveyed using REDCap(r). For all quantitative data, proportions of
      responses were calculated and analyzed using Microsoft Excel 2013(r). The authors
      analyzed qualitative data using a conventional content analysis approach. The
      survey was sent to 74 educators; 39 (53%) responses were received. Most (62%; n =
      24) of the pediatric residency programs that offer GHE reported that their
      institution had a social media policy. About one-third (34%; n = 13) of
      respondents stated that their programs had social media guidelines that pertained
      specifically to GHE and fewer indicated that social media guidelines were
      included in their programs' GHE predeparture curricula (32%; n = 12). This study
      found that most of the residency programs surveyed had social media guidelines,
      but few had guidelines applicable or specific to GHE. Informed by this study and
      a literature review, the authors propose template language for a social media
      guideline with considerations for social media use in the context of GHE.

PMID- 30226147
TI  - Case Report: Bothrops lanceolatus Snakebite Surgical Management-Relevance of
      Fasciotomy.
AB  - Bothrops lanceolatus is an endemic Crotalidae species in Martinique, where
      approximately 30 cases of envenoming are managed yearly. Envenoming
      characteristics from Bothrops species include local tissue damage, systemic
      bleeding, and hemodynamic alterations. We hereby report a case of severe
      envenomation following B. lanceolatus snakebite to the right calf. Severe local
      manifestations developed progressively up to the lower limb despite adequate
      antivenom therapy. Systemic manifestations of venom also occurred, resulting in
      intensive care therapy. Surgery exploration revealed soft tissue necrosis,
      friability of the deep fascia, and myonecrosis. The patient needed multiple
      debridement procedures and fasciotomy of all leg compartments and anterior
      compartment of the thigh. Diagnosis of necrotizing fasciitis was confirmed by
      positive Aeromonas hydrophila blood cultures. This clinical case illustrates that
      major soft tissue infection, including necrotizing fasciitis may occur after
      snakebite. Abnormal coagulation tests should not delay surgical management, as
      severe envenoming is a life-threatening condition.

PMID- 30226148
TI  - Onchocerciasis-Associated Epilepsy with Head Nodding Seizures-Nodding Syndrome: A
      Case Series of 15 Patients from Western Uganda, 1994.
AB  - Nodding syndrome (NS) is an encephalopathy characterized by the core symptom of
      epileptic head nodding seizures, affecting children at the age between 3 and 18
      years in distinct areas of tropical Africa. A consistent correlation with
      onchocerciasis was found, but so far, the causation of NS has not been fully
      clarified. With a systematic analysis of features of a cohort of epilepsy
      patients examined in the Itwara onchocerciasis focus of western Uganda in 1994,
      we provide evidence that NS actually occurred in this area at this time, and we
      demonstrate a correlation between prevalence of NS and that of onchocerciasis in
      different villages. Following the elimination of onchocerciasis by community
      directed treatment with ivermectin and ground larviciding, our data provide a
      baseline to examine the question whether NS will disappear once its putative
      cause has been removed.

PMID- 30226149
TI  - To End TB, First-Ever High-Level Meeting on Tuberculosis Must Address Stigma.
AB  - World leaders gather to consolidate their commitment to ending tuberculosis (TB).
      Vital to the success of renewed efforts is an overdue recognition of the
      pervasive and pernicious influence of TB stigma. TB stigma is sustained in
      structures, policies, traditions, and norms. Innovative modifications to
      infection control, drug dispensing, and surveillance practices are required to
      increase demand for TB screening and effective therapeutic alliances among those
      diagnosed. The authors argue that reducing TB stigma requires a scientific and
      inclusive process, with prominent roles for TB survivors and a willingness to
      integrate and learn from other stigmatized conditions.

PMID- 30226150
TI  - Case Report: A Common Source Outbreak of Anisakidosis in the United States and
      Postexposure Prophylaxis of Family Collaterals.
AB  - We present a case of intussusception with complete small bowel obstruction caused
      by intestinal anisakidosis requiring surgical resection. A 30-year-old man
      presented with acute onset of severe abdominal pain 3 days after eating home
      cured salmon gravlax. Despite surgery, the patient developed recurrent abdominal
      pain on two occasions with evidence of continued inflammation proximal to the
      surgical anastomosis. He was then treated with albendazole and prednisone, and
      symptoms improved. A decision was made to prophylactically treat two asymptomatic
      family members who also consumed home-cured gravlax with albendazole, resulting
      in one individual passing an intact Anisakis worm in her stool. We suggest that
      albendazole therapy could be considered as a therapy for continued symptoms of
      anisakidosis and postexposure prophylaxis of Anisakis larvae ingestion from a
      common source.

PMID- 30226151
TI  - Environmental Determinants of Hemorrhagic Fever with Renal Syndrome in High-Risk
      Counties in China: A Time Series Analysis (2002-2012).
AB  - The transmission pattern of hemorrhagic fever with renal syndrome (HFRS) is
      associated with environmental conditions, including meteorological factors and
      land-cover. In the present study, the association between HFRS and environmental
      factors (including maximum temperature, relative humidity, rainfall, and
      normalized difference vegetation index) were explored in two typical counties in
      Northeast and two counties in Northwest China with severe HFRS outbreaks by using
      seasonal autoregressive integrated moving average model with exogenous variables
      (SARIMAX). The results showed that rainfall with 3- to 4-month lag was closely
      associated with HFRS in the two counties in Northeast China, whereas relative
      humidity with 1- or 5-month lag significantly impacts HFRS transmission in the
      two counties in Northwest China. Moreover, the SARIMAX models exhibit accurate
      forecasting ability of HFRS cases. Our findings provide scientific support for
      local HFRS monitoring and control, and the development of a HFRS early warning
      system.

PMID- 30226152
TI  - Impact of Chronic Kidney Disease on Chikungunya Virus Infection Clinical
      Manifestations and Outcome: Highlights during an Outbreak in Northeastern Brazil.
AB  - The northeastern region of Brazil has faced in the last 2 years the largest
      outbreak of chikungunya virus (CHIKV) infection in its history. There are still
      few studies on kidney involvement in CHIKV. The aim of this study is to describe
      the impact of chronic kidney disease (CKD) on CHIKV clinical manifestations and
      outcome. This is a cross-sectional study conducted in the State of Ceara,
      northeastern Brazil, including all registered cases of CHIKV infection in the
      period from January 2016 to December 2017. Clinical manifestations were collected
      from the notification reports from official data bank from the State Secretary of
      Health of Ceara: National System of Diseases Notification and Laboratory Manager.
      A total of 182,731 cases were notified. Patients' mean age was 32.4 +/- 14.6
      years, and 62.2% were female. The most common clinical manifestations were fever
      (88.6%), headache (72.9%), intense arthralgia (69.5%), and myalgia (65.6%).
      Hospital admission was required for 3,080 cases (3.3%), and death occurred in 383
      cases (0.2%). Chronic kidney disease was reported in 691 cases (0.3%). Patients
      with CKD had a higher frequency of almost all clinical manifestations, including
      fever, myalgia, exanthema, vomiting, nausea, back pain, conjunctivitis,
      arthritis, severe arthralgia, petechiae, and retro-orbital pain. They also had a
      significantly higher frequency of diabetes, hematological disorders, liver
      diseases, hypertension, peptic ulcer disease, and autoimmune diseases. Mortality
      was significantly higher among CKD patients than patients without CKD (3.0%
      versus 0.2%, P < 0.0001).

PMID- 30226153
TI  - Praziquantel Resistance in the Zoonotic Cestode Dipylidium caninum.
AB  - Dipylidium caninum is a cosmopolitan cestode infecting dogs, cats, and humans.
      Praziquantel is a highly effective cestocidal drug and resistance in adult
      cestodes has not been reported. From 2016 to 2018, a population of dogs with
      cestode infections that could not be eliminated despite multiple treatments with
      praziquantel or epsiprantel was identified. Cases of D. caninum were clinically
      resistant to praziquantel and could not be resolved despite increasing the dose,
      frequency, and duration of treatment. Resistant isolates were identified and
      characterized by sequencing the 28S, 12S, and voltage-gated calcium channel beta
      subunit genes. Cases were only resolved following treatment with nitroscanate or
      a compounded pyrantel/praziquantel/oxantel product. Clinicians should be aware of
      this alarming development as treatment options for cestodes are limited in both
      human and veterinary medicine.

PMID- 30226154
TI  - Tuberculosis Treatment Monitoring by Video Directly Observed Therapy in 5 Health
      Districts, California, USA.
AB  - We assessed video directly observed therapy (VDOT) for monitoring tuberculosis
      treatment in 5 health districts in California, USA, to compare adherence between
      174 patients using VDOT and 159 patients using in-person directly observed
      therapy (DOT). Multivariable linear regression analyses identified participant
      reported sociodemographics, risk behaviors, and treatment experience associated
      with adherence. Median participant age was 44 (range 18-87) years; 61% of
      participants were male. Median fraction of expected doses observed (FEDO) among
      VDOT participants was higher (93.0% [interquartile range (IQR) 83.4%-97.1%]) than
      among patients receiving DOT (66.4% [IQR 55.1%-89.3%]). Most participants (96%)
      would recommend VDOT to others; 90% preferred VDOT over DOT. Lower FEDO was
      independently associated with US or Mexico birth, shorter VDOT duration, finding
      VDOT difficult, frequently taking medications while away from home, and having
      video-recording problems (p<0.05). VDOT cost 32% (range 6%-46%) less than DOT.
      VDOT was feasible, acceptable, and achieved high adherence at lower cost than
      DOT.

PMID- 30226155
TI  - Candida auris in Healthcare Facilities, New York, USA, 2013-2017.
AB  - Candida auris is an emerging yeast that causes healthcare-associated infections.
      It can be misidentified by laboratories and often is resistant to antifungal
      medications. We describe an outbreak of C. auris infections in healthcare
      facilities in New York City, New York, USA. The investigation included laboratory
      surveillance, record reviews, site visits, contact tracing with cultures, and
      environmental sampling. We identified 51 clinical case-patients and 61 screening
      case-patients. Epidemiologic links indicated a large, interconnected web of
      affected healthcare facilities throughout New York City. Of the 51 clinical case
      patients, 23 (45%) died within 90 days and isolates were resistant to fluconazole
      for 50 (98%). Of screening cultures performed for 572 persons (1,136 total
      cultures), results were C. auris positive for 61 (11%) persons. Environmental
      cultures were positive for samples from 15 of 20 facilities. Colonization was
      frequently identified during contact investigations; environmental contamination
      was also common.

PMID- 30226156
TI  - Human Pegivirus in Patients with Encephalitis of Unclear Etiology, Poland.
AB  - Human pegivirus (HPgV), previously called hepatitis G virus or GB virus C, is a
      lymphotropic virus with undefined pathology. Because many viruses from the family
      Flaviviridae, to which HPgV belongs, are neurotropic, we studied whether HPgV
      could infect the central nervous system. We tested serum and cerebrospinal fluid
      samples from 96 patients with a diagnosis of encephalitis for a variety of
      pathogens by molecular methods and serology; we also tested for autoantibodies
      against neuronal antigens. We found HPgV in serum and cerebrospinal fluid from 3
      patients who had encephalitis of unclear origin; that is, all the markers that
      had been tested were negative. Single-strand confirmation polymorphism and next
      generation sequencing analysis revealed differences between the serum and
      cerebrospinal fluid-derived viral sequences, which is compatible with the
      presence of a separate HPgV compartment in the central nervous system. It is
      unclear whether HPgV was directly responsible for encephalitis in these patients.

PMID- 30226157
TI  - Molecular Evolution, Diversity, and Adaptation of Influenza A(H7N9) Viruses in
      China.
AB  - The substantial increase in prevalence and emergence of antigenically divergent
      or highly pathogenic influenza A(H7N9) viruses during 2016-17 raises concerns
      about the epizootic potential of these viruses. We investigated the evolution and
      adaptation of H7N9 viruses by analyzing available data and newly generated virus
      sequences isolated in Guangdong Province, China, during 2015-2017. Phylogenetic
      analyses showed that circulating H7N9 viruses belong to distinct lineages with
      differing spatial distributions. Hemagglutination inhibition assays performed on
      serum samples from patients infected with these viruses identified 3 antigenic
      clusters for 16 strains of different virus lineages. We used ancestral sequence
      reconstruction to identify parallel amino acid changes on multiple separate
      lineages. We inferred that mutations in hemagglutinin occur primarily at sites
      involved in receptor recognition or antigenicity. Our results indicate that
      highly pathogenic strains likely emerged from viruses circulating in eastern
      Guangdong Province during March 2016 and are associated with a high rate of
      adaptive molecular evolution.

PMID- 30226158
TI  - Multilocus Sequence Typing of Mycoplasma pneumoniae, Japan, 2002-2016.
AB  - In Japan, Mycoplasma pneumoniae resistance to macrolides is high. To compare
      sequence types (STs) of susceptible and resistant isolates, we performed
      multilocus sequence typing for 417 isolates obtained in Japan during 2002-2016.
      The most prevalent ST overall was ST3, for macrolide-resistant was ST19, and for
      macrolide-susceptible were ST14 and ST7.

PMID- 30226159
TI  - Evaluation of Effectiveness of a Community-Based Intervention for Control of
      Dengue Virus Vector, Ouagadougou, Burkina Faso.
AB  - We evaluated the effectiveness of a community-based intervention for dengue
      vector control in Ouagadougou, the capital city of Burkina Faso. Households in
      the intervention (n = 287) and control (n = 289) neighborhoods were randomly
      sampled and the outcomes collected before the intervention (October 2015) and
      after the intervention (October 2016). The intervention reduced residents'
      exposure to dengue vector bites (vector saliva biomarker difference -0.08 [95% CI
      -0.11 to -0.04]). The pupae index declined in the intervention neighborhood (from
      162.14 to 99.03) and increased in the control neighborhood (from 218.72 to
      255.67). Residents in the intervention neighborhood were less likely to associate
      dengue with malaria (risk ratio 0.70 [95% CI 0.58-0.84]) and had increased
      knowledge about dengue symptoms (risk ratio 1.44 [95% CI 1.22-1.69]). Our study
      showed that well-planned, evidence/community-based interventions that control
      exposure to dengue vectors are feasible and effective in urban settings in Africa
      that have limited resources.

PMID- 30226160
TI  - Evaluation of Nowcasting for Detecting and Predicting Local Influenza Epidemics,
      Sweden, 2009-2014.
AB  - The growing availability of big data in healthcare and public health opens
      possibilities for infectious disease control in local settings. We prospectively
      evaluated a method for integrated local detection and prediction (nowcasting) of
      influenza epidemics over 5 years, using the total population in Ostergotland
      County, Sweden. We used routine health information system data on influenza
      diagnosis cases and syndromic telenursing data for July 2009-June 2014 to
      evaluate epidemic detection, peak-timing prediction, and peak-intensity
      prediction. Detection performance was satisfactory throughout the period, except
      for the 2011-12 influenza A(H3N2) season, which followed a season with influenza
      B and pandemic influenza A(H1N1)pdm09 virus activity. Peak-timing prediction
      performance was satisfactory for the 4 influenza seasons but not the pandemic.
      Peak-intensity levels were correctly categorized for the pandemic and 2 of 4
      influenza seasons. We recommend using versions of this method modified with
      regard to local use context for further evaluations using standard methods.

PMID- 30226161
TI  - Influenza Transmission Dynamics in Urban Households, Managua, Nicaragua, 2012
      2014.
AB  - During August 2012-November 2014, we conducted a case ascertainment study to
      investigate household transmission of influenza virus in Managua, Nicaragua. We
      collected up to 5 respiratory swab samples from each of 536 household contacts of
      133 influenza virus-infected persons and assessed for evidence of influenza virus
      transmission. The overall risk for influenza virus infection of household
      contacts was 15.7% (95% CI 12.7%-19.0%). Oseltamivir treatment of index patients
      did not appear to reduce household transmission. The mean serial interval for
      within-household transmission was 3.1 (95% CI 1.6-8.4) days. We found the
      transmissibility of influenza B virus to be higher than that of influenza A virus
      among children. Compared with households with <4 household contacts, those with
      >4 household contacts appeared to have a reduced risk for infection. Further
      research is needed to model household influenza virus transmission and design
      interventions for these settings.

PMID- 30226162
TI  - Rapid Increase in Carriage Rates of Enterobacteriaceae Producing Extended
      Spectrum beta-Lactamases in Healthy Preschool Children, Sweden.
AB  - By collecting and analyzing diapers, we identified a >6-fold increase in carriage
      of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae for
      healthy preschool children in Sweden (p<0.0001). For 6 of the 50 participating
      preschools, the carriage rate was >40%. We analyzed samples from 334 children and
      found 56 containing >1 ESBL producer. The prevalence in the study population
      increased from 2.6% in 2010 to 16.8% in 2016 (p<0.0001), and for 6 of the 50
      participating preschools, the carriage rate was >40%. Furthermore, 58% of the
      ESBL producers were multidrug resistant, and transmission of ESBL-producing and
      non-ESBL-producing strains was observed at several of the preschools. Toddlers
      appear to be major carriers of ESBL producers in Sweden.

PMID- 30226163
TI  - Cronobacter spp. in Common Breast Milk Substitutes, Bogota, Colombia.
AB  - In Bogota, Colombia, a large number of babies are fed with breast milk
      substitutes made from corn and plantain starch. We found 34.3% of tested samples
      to be contaminated with Cronobacter spp.; C. sakazakii was the most recovered
      species. Our findings underscore the risk for contamination of breast milk
      substitutes.

PMID- 30226164
TI  - Zika Virus Infection during Pregnancy and Effects on Early Childhood Development,
      French Polynesia, 2013-2016.
AB  - Congenital Zika virus syndrome consists of a large spectrum of neurologic
      abnormalities seen in infants infected with Zika virus in utero. However, little
      is known about the effects of Zika virus intrauterine infection on the
      neurocognitive development of children born without birth defects. Using a case
      control study design, we investigated the temporal association of a cluster of
      congenital defects with Zika virus infection. In a nested study, we also assessed
      the early childhood development of children recruited in the initial study as
      controls who were born without known birth defects,. We found evidence for an
      association of congenital defects with both maternal Zika virus seropositivity
      (time of infection unknown) and symptomatic Zika virus infection during
      pregnancy. Although the early childhood development assessment found no excess
      burden of developmental delay associated with maternal Zika virus infection,
      larger, longer-term studies are needed.

PMID- 30226165
TI  - Two Community Clusters of Legionnaires' Disease Directly Linked to a Biologic
      Wastewater Treatment Plant, the Netherlands.
AB  - A biologic wastewater treatment plant was identified as a common source for 2
      consecutive Legionnaires' disease clusters in the Netherlands in 2016 and 2017.
      Sequence typing and transmission modeling indicated direct and long-distance
      transmission of Legionella, indicating this source type should also be
      investigated in sporadic Legionnaires' disease cases.

PMID- 30226166
TI  - Acute Encephalitis with Atypical Presentation of Rubella in Family Cluster,
      India.
AB  - We report 3 atypical rubella cases in a family cluster in India. The index case
      patient showed only mild febrile illness, whereas the other 2 patients showed
      acute encephalitis and died of the disease. We confirmed rubella in the index and
      third cases using next-generation sequencing and IgM.

PMID- 30226167
TI  - Transmission Dynamics of Highly Pathogenic Avian Influenza Virus A(H5Nx) Clade
      2.3.4.4, North America, 2014-2015.
AB  - Eurasia highly pathogenic avian influenza virus (HPAIV) H5 clade 2.3.4.4 emerged
      in North America at the end of 2014 and caused outbreaks affecting >50 million
      poultry in the United States before eradication in June 2015. We investigated the
      underlying ecologic and epidemiologic processes associated with this viral spread
      by performing a comparative genomic study using 268 full-length genome sequences
      and data from outbreak investigations. Reassortant HPAIV H5N2 circulated in wild
      birds along the Pacific flyway before several spillover events transmitting the
      virus to poultry farms. Our analysis suggests that >3 separate introductions of
      HPAIV H5N2 into Midwest states occurred during March-June 2015; transmission to
      Midwest poultry farms from Pacific wild birds occurred ~1.7-2.4 months before
      detection. Once established in poultry, the virus rapidly spread between turkey
      and chicken farms in neighboring states. Enhanced biosecurity is required to
      prevent the introduction and dissemination of HPAIV across the poultry industry.

PMID- 30226168
TI  - External Quality Assessment for Zika Virus Molecular Diagnostic Testing, Brazil.

PMID- 30226169
TI  - Severe Respiratory Illness Outbreak Associated with Human Coronavirus NL63 in a
      Long-Term Care Facility.
AB  - We describe an outbreak of severe respiratory illness associated with human
      coronavirus NL63 in a long-term care facility in Louisiana in November 2017. Six
      of 20 case-patients were hospitalized with pneumonia, and 3 of 20 died.
      Clinicians should consider human coronavirus NL63 for patients in similar
      settings with respiratory disease.

PMID- 30226170
TI  - Mycobacterium caprae Infection in Captive Borneo Elephant, Japan.
AB  - In 2016, disseminated tuberculosis caused by Mycobacterium caprae was diagnosed
      in a captive Borneo elephant in Japan. The bacterium was initially identified
      from clinical isolates. An isolate collected during a relapse showed isoniazid
      monoresistance and a codon 315 katG mutation.

PMID- 30226171
TI  - Effectiveness of Whole, Inactivated, Low Pathogenicity Influenza A(H7N9) Vaccine
      against Antigenically Distinct, Highly Pathogenic H7N9 Virus.
AB  - The recent emergence of highly pathogenic influenza A(H7N9) variants poses a
      great risk to humans. We show that ferrets vaccinated with low pathogenicity H7N9
      virus vaccine do not develop severe symptoms after infection with an
      antigenically distinct, highly pathogenic H7N9 virus. These results demonstrate
      the protective benefits of this H7N9 vaccine.

PMID- 30226172
TI  - Emerging Enteroviruses Causing Hand, Foot and Mouth Disease, China, 2010-2016.
AB  - Coxsackievirus A6 emerged as one of the predominant causative agents of hand,
      foot and mouth disease epidemics in many provinces of China in 2013 and 2015.
      This virus strain accounted for 25.9% of mild and 15.2% of severe cases in 2013
      and 25.8% of mild and 16.9% of severe cases in 2015.

PMID- 30226173
TI  - Psychrobacter sanguinis Wound Infection Associated with Marine Environment
      Exposure, Washington, USA.
AB  - We report a 26-year-old man with Psychrobacter sanguinis cellulitis of a wound
      sustained during ocean fishing in Washington, USA, in 2017. Psychrobacter spp.
      are opportunistic pathogens found in a wide range of environments. Clinicians
      should be aware of Psychrobacter spp. and perform 16S rRNA sequencing if this
      pathogen is suspected.

PMID- 30226174
TI  - Simple Estimates for Local Prevalence of Latent Tuberculosis Infection, United
      States, 2011-2015.
AB  - We used tuberculosis genotyping results to derive estimates of prevalence of
      latent tuberculosis infection in the United States. We estimated <1% prevalence
      in 1,981 US counties, 1%-<3% in 785 counties, and >3% in 377 counties. This
      method for estimating prevalence could be applied in any jurisdiction with an
      established tuberculosis surveillance system.

PMID- 30226175
TI  - Influenza C Virus in Cattle with Respiratory Disease, United States, 2016-2018.
AB  - We identified influenza C virus (ICV) in samples from US cattle with bovine
      respiratory disease through real-time PCR testing and sequencing. Bovine ICV
      isolates had high nucleotide identities (~98%) with each other and were closely
      related to human ICV strains (~95%). Further research is needed to determine
      bovine ICV's zoonotic potential.

PMID- 30226176
TI  - Genetic Diversity and Antimicrobial Drug Resistance of Serotype VI Group B
      Streptococcus, Canada.
AB  - Two genetically dissimilar sequence type 1 clades dominate the serotype VI group
      B Streptococcus population of strains causing invasive disease in Canada.
      Isolates of this rare serotype, recovered mainly from adult patients, were all
      susceptible to penicillin and vancomycin. However, we observed resistance to
      erythromycin and clindamycin.

PMID- 30226177
TI  - Non-cyp51A Azole-Resistant Aspergillus fumigatus Isolates with Mutation in HMG
      CoA Reductase.
AB  - The recent increase in azole-resistant Aspergillus fumigatus is a global concern.
      Identifying the mutations that confer azole resistance is essential for
      developing novel methods for prompt diagnosis and effective drug treatment. We
      screened A. fumigatus clinical isolates for novel mutations conferring azole
      resistance. We compared the genomic sequences of susceptible and resistant
      isolates without mutations in cyp51A (non-cyp51A) and found mutations in hmg1 and
      erg6 involved in ergosterol biosynthesis. We also found the novel mutations in
      these genes in azole-resistant isolates with different genetic backgrounds. The
      resistant isolates with mutations in hmg1 showed increased intracellular
      ergosterol levels compared with susceptible isolates. This finding supports the
      concept that the ergosterol level is a determinant for resistance to any class of
      azoles. Multiple isolates with increased resistance to azole possessed a mutation
      in hmg1, indicating that this mutation is widely present in non-cyp51A azole
      resistant A. fumigatus.

PMID- 30226178
TI  - Revisiting Influenza Vaccination Exemption.
AB  - Serious adverse events after immunizations are rare. We review the case of a man
      who, 50 years earlier, experienced a serious adverse neurologic event 2 weeks
      after receiving influenza vaccine. He had received no subsequent seasonal
      influenza vaccinations, but after the risks and benefits were considered, he was
      vaccinated without adverse event that season.

PMID- 30226179
TI  - Invasive Pneumococcal Disease in Refugee Children, Germany.
AB  - Refugee children in Germany are not routinely given a pneumococcal conjugate
      vaccine. Cases of invasive pneumococcal disease (IPD) in 21 refugee children were
      compared with those in 405 Germany-born children for 3 pneumococcal seasons.
      Refugee children had significantly higher odds of vaccine-type IPD and multidrug
      resistant IPD than did Germany-born children.

PMID- 30226180
TI  - Clinical Isolation and Identification of Haematospirillum jordaniae.
AB  - A clinical case study involving a man (35-49 years of age) with wounds to his
      lower right extremity. An isolate was sent to the Delaware Public Health
      Laboratory for confirmatory testing by genetic analysis of the 16S gene. Testing
      identified the isolate as a novel genus and species, Haematospirillum jordaniae.

PMID- 30226181
TI  - New Reassortant Clade 2.3.4.4b Avian Influenza A(H5N6) Virus in Wild Birds, South
      Korea, 2017-18.
AB  - We isolated new reassortant avian influenza A(H5N6) viruses from feces of wild
      waterfowl in South Korea during 2017-18. Phylogenetic analysis suggested that
      reassortment occurred between clade 2.3.4.4b H5N8 and Eurasian low pathogenicity
      avian influenza viruses circulating in wild birds. Dissemination to South Korea
      during the 2017 fall migratory season followed.

PMID- 30226182
TI  - Community-Acquired Staphylococcus argenteus Sequence Type 2250 Bone and Joint
      Infection, France, 2017.
AB  - We report a rare case of Staphylococcus argenteus bone and joint infection in a 9
      year-old boy in France. His finger arthritis was complicated by osteitis 5 weeks
      later, which resulted in a secondary intervention. This case indicates the
      virulence of S. argenteus, an emerging pathogen whose clinical effects are poorly
      described.

PMID- 30226183
TI  - Molecular Typing and Antifungal Susceptibility of Candida viswanathii, India.
AB  - We report invasive candidiasis caused by Candida viswanathii over 2 time periods
      during 2013-2015 in a tertiary care hospital in Chandigarh, India. Molecular
      typing revealed multiple clusters of the isolates. We detected high MICs for
      fluconazole in the second time period.

PMID- 30226184
TI  - Rapid Spread of Pneumococcal Nonvaccine Serotype 7C Previously Associated with
      Vaccine Serotype 19F, England and Wales.
AB  - We observed a sudden and rapid increase in rare invasive pneumococcal disease
      serotype 7C, from an annual average of 3 cases during 2000-01 through 2015-16 to
      29 cases in 2016-17. The increase was caused almost entirely by clonal expansion
      of sequence type 177, previously associated with vaccine serotype 19F.

PMID- 30226185
TI  - Introduction of Eurasian-Origin Influenza A(H8N4) Virus into North America by
      Migratory Birds.
AB  - We identified a Eurasian-origin influenza A(H8N4) virus in North America by
      sampling wild birds in western Alaska, USA. Evidence for repeated introductions
      of influenza A viruses into North America by migratory birds suggests that
      intercontinental dispersal might not be exceedingly rare and that our
      understanding of viral establishment is incomplete.

PMID- 30226186
TI  - Fatal Cronobacter sakazakii Sequence Type 494 Meningitis in a Newborn, Brazil.
AB  - We describe a case of infection with Cronobacter sakazakii sequence type 494
      causing bacteremia and meningitis in a hospitalized late premature infant in
      Brazil. We conducted microbiological analyses on samples of powdered infant
      formula from the same batch as formula ingested by the infant but could not
      identify the source of contamination.

PMID- 30226187
TI  - Mapping Histoplasma capsulatum Exposure, United States.
AB  - Maps of Histoplasma capsulatum infection prevalence were created 50 years ago;
      since then, the environment, climate, and anthropogenic land use have changed
      drastically. Recent outbreaks of acute disease in Montana and Nebraska, USA,
      suggest shifts in geographic distribution, necessitating updated prevalence maps.
      To create a weighted overlay geographic suitability model for Histoplasma, we
      used a geographic information system to combine satellite imagery integrating
      land cover use (70%), distance to water (20%), and soil pH (10%). We used
      logistic regression modeling to compare our map with state-level histoplasmosis
      incidence data from a 5% sample from the Centers for Medicare and Medicaid
      Services. When compared with the state-based Centers data, the predictive
      accuracy of the suitability score-predicted states with high and mid-to-high
      histoplasmosis incidence was moderate. Preferred soil environments for
      Histoplasma have migrated into the upper Missouri River basin. Suitability score
      mapping may be applicable to other geographically specific infectious vectors.

PMID- 30226188
TI  - Frequent Genetic Mismatch between Vaccine Strains and Circulating Seasonal
      Influenza Viruses, Hong Kong, China, 1996-2012.
AB  - The World Health Organization selects influenza vaccine compositions biannually
      to cater to peaks in temperate regions. In tropical and subtropical regions,
      where influenza seasonality varies and epidemics can occur year-round, the choice
      of vaccine remains uncertain. Our 17-year molecular epidemiologic survey showed
      that most influenza A(H3N2) (9/11) and B (6/7) vaccine strains had circulated in
      East Asia >1 year before inclusion into vaccines. Northern Hemisphere vaccine
      strains and circulating strains in East Asia were closely matched in 7 (20.6%) of
      34 seasons for H3N2 and 5 (14.7%) of 34 seasons for B. Southern Hemisphere
      vaccines also had a low probability of matching (H3N2, 14.7%; B, 11.1%). Strain
      drift among seasons was common (H3N2, 41.2%; B, 35.3%), and biannual vaccination
      strategy (Northern Hemisphere vaccines in November followed by Southern
      Hemisphere vaccines in May) did not improve matching. East Asia is an important
      contributor to influenza surveillance but often has mismatch between vaccine and
      contemporarily circulating strains.

PMID- 30226189
TI  - Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins.
AB  - Human gut Bacteroides use surface-exposed lipoproteins to bind and metabolize
      complex polysaccharides. Although vitamins and other nutrients are also essential
      for commensal fitness, much less is known about how commensal bacteria compete
      with each other or the host for these critical resources. Unlike in Escherichia
      coli, transport loci for vitamin B12 (cobalamin) and other corrinoids in human
      gut Bacteroides are replete with conserved genes encoding proteins whose
      functions are unknown. Here we report that one of these proteins, BtuG, is a
      surface-exposed lipoprotein that is essential for efficient B12 transport in B.
      thetaiotaomicron. BtuG binds B12 with femtomolar affinity and can remove B12 from
      intrinsic factor, a critical B12 transport protein in humans. Our studies suggest
      that Bacteroides use surface-exposed lipoproteins not only for capturing
      polysaccharides, but also to acquire key vitamins in the gut.

PMID- 30226191
TI  - Galectin-3 aggravates experimental polymicrobial sepsis by impairing neutrophil
      recruitment to the infectious focus.
AB  - Sepsis is an overwhelming systemic inflammation resulting from an uncontrolled
      infection that causes extensive tissue damage, organ dysfunction and eventually
      death. A growing body of evidence indicates that impaired neutrophil migration to
      the site of infection is associated with poor outcome in sepsis. Here we show
      that galectin-3 (Gal-3), an endogenous glycan-binding protein, plays a critical
      role in sepsis outcome. We found that serum Gal-3 concentration increased in
      patients with septic shock and mice undergoing sepsis induced by cecal ligation
      and puncture (CLP). Mice deficient in Gal-3 (Gal-3 KO) are more resistant to
      sepsis induced by CLP, showing lower levels of biochemical markers and neutrophil
      infiltration for organ injury/dysfunction than those observed in wild-type mice
      (WT). Furthermore, Gal-3 KO mice show an increased number of neutrophils in the
      primary focus of infection and reduced bacterial loads in the peritoneal cavity,
      blood, and lungs. Mechanistically, blood neutrophils from septic mice show higher
      levels of surface-bound Gal-3 than neutrophils from naive mice. The deficiency of
      Gal-3 was associated with increased rolling and adhesion of these cells in
      mesenteric venules. Our results indicate that Gal-3, secreted during sepsis,
      inhibits neutrophil migration into the infectious focus, which promotes the
      bacterial spread and worsens the outcome of sepsis.

PMID- 30226190
TI  - Experimental evaluation of the importance of colonization history in early-life
      gut microbiota assembly.
AB  - The factors that govern assembly of the gut microbiota are insufficiently
      understood. Here, we test the hypothesis that inter-individual microbiota
      variation can arise solely from differences in the order and timing by which the
      gut is colonized early in life. Experiments in which mice were inoculated in
      sequence either with two complex seed communities or a cocktail of four bacterial
      strains and a seed community revealed that colonization order influenced both the
      outcome of community assembly and the ecological success of individual
      colonizers. Historical contingency and priority effects also occurred in Rag1-/-
      mice, suggesting that the adaptive immune system is not a major contributor to
      these processes. In conclusion, this study established a measurable effect of
      colonization history on gut microbiota assembly in a model in which host and
      environmental factors were strictly controlled, illuminating a potential cause
      for the high levels of unexplained individuality in host-associated microbial
      communities.

PMID- 30226192
TI  - How I do in front of an hemolytic anemia of unknown etiology?
AB  - The most frequent causes of hemolytic anemias are immune or infectious diseases,
      drug induced hemolysis, thrombotic microangiopathies, hereditary spherocytosis,
      glucose-6-phosphate dehydrogenase or pyruvate kinase deficiencies, thalassemia's
      and sickle cell disease. Sometimes no cause is found because a rarer etiology is
      involved. The goal of this review is to remember some unfrequent constitutional
      or acquired causes and to point out difficulties to avoid wrong interpretations
      of analysis results.

PMID- 30226194
TI  - Evaluation of the effect of hemolysis, bilirubin, lipemy, glucosis and natrium on
      mean concentration of hemoglobin (XN 2000(r) Sysmex(r)).
AB  - We evaluated the effect of haemolysis, bilirubin, lipemia, hyperglycemia and
      natremia on mean corpuscular haemoglobin concentration (MCHC) measured by XN
      2000(r) (Sysmex(r)). Our evaluation had shown than correction is necessary for
      haemolysis and lipemia but not for icterus. There were not possible to reproduce
      variation of MCHC with hyperglycemia or variation of natremia. Blood smears show
      red blood cells abnormalities.

PMID- 30226193
TI  - Development of digital PCR molecular tests for clinical practice: principles,
      practical implementation and recommendations.
AB  - Digital PCR (dPCR) is a 3rd generation technology that complements traditional
      end-point PCR and real-time PCR. It was developed to overcome certain limitations
      of conventional amplification techniques, in particular for the detection of
      small amounts of nucleic acids and/or rare variants. This technology is in a full
      swing because of its high sensitivity and major applications in various domains
      such as oncology, transplantation or non-invasive prenatal testing. Consequently,
      PCRd also has great interest in many areas of medical biology, particularly for
      clinical applications aiming at detecting and quantifying specific genetic or
      epigenetic alterations of nucleic acids, even with specimens containing very low
      concentration of the nucleic acids of interest (e.g. liquid biopsies). However,
      this technique requires a good training of users and compliance with certain
      precautions. A lack in such a knowledge can lead to many errors in the conduct of
      the experiment and the interpretation of the results. In this review, we present
      the context in which this technology has emerged by describing in particular its
      principle and the main factors that can influence the quality of the analysis.
      Then, we propose a number of practical recommendations for the implementation of
      a test based on dPCR in clinical laboratories with an eye on quality
      requirements.

PMID- 30226195
TI  - Which are the significance of low level of glycated hemoglobin A1c?
AB  - Glycated hemoglobin A1c (HbA1c) reflects the mean blood glucose over the lifespan
      of red blood cells and has become a valuable tool both for diagnosis and
      monitoring of diabetes. Nevertheless, some factors may under-estimate the HbA1c
      value, compromising its application. The aim of this retrospective study was to
      evaluate the incidence rate of HbA1c lower than 4% and to identify some clinical
      and biological factors that can potentially reduce the HbA1c level. Between
      January 1st 2015 and October 1st 2017, we selected 17 patients with a HbA1c level
      lower than 4% that were measured in our laboratory of biochemistry at the
      university medical center of Caen. From the medical records, we identified
      medical conditions, treatments and biological parameters that could potentially
      explain a decrease of HbA1c level. Meanwhile the measurement of HbA1c, 8/16
      patients had hemoglobin level lower than 100 g/L and 5/6 presented with
      reticulocytosis (>100 G/L). Ten patients over 17 suffered from hepatopathy
      (cirrhosis from various etiologies) with abnormal liver blood tests for 12
      patients. Two patients showed hemolytic anemia and another one was investigated
      for hypoglycemia due to congenital hyperinsulinism. Finally, 3 patients were
      treated with drugs known to lower HbA1c levels. True hypoglycemia periods but
      also other circumstances which are known to alter erythrocytes lifespan or the
      glycation process may decrease HbA1c level. Such biological result should be
      critically interpreted and alternative biological markers should be considered.

PMID- 30226196
TI  - Evaluation of the capillary assay of C-reactive protein (CRP) through the lenght
      of consultation in pediatric emergencies and its economic impact.
AB  - Fever is a frequent reason for consultation in pediatric emergency departments
      and raises the question of biological and radiological examinations. Rapidly
      obtaining the result of C-reactive protein (CRP) level is essential in front of
      the steady increase of the number of visits. We carried out a prospective study
      within the pediatric emergency department of the University Hospital of Clermont
      Ferrand from January to April 2017, in order to evaluate the interest of the
      capillary CRP in point of care (POCT). In two periods, 68 patients (28 controls
      without and 40 cases with capillary CRP assayed on a Afinion(r) AS100) with naked
      fever greater than 48 hours were included. After a study of the analytical
      performances of Afinion(r) and a verification of the homogeneity and the
      comparability of the two groups on clinical criteria (age, sex, duration of the
      fever, antibiotics treatment) and biological (values of CRP), the interest of the
      CRP in POCT was evaluated. In the POCT group, a significant drop in the median of
      the emergency room consultation time (60 (IQR 33-125) versus 180 (IQR 158-208)
      minutes), the number of biological acts by patient (1 (IQR 1-3) versus 7 (IQR 3
      8)), the global cost of biological and radiological examinations per patient (5.4
      (IQR 5.4-32.6) versus 153.8 (IQR 46.9-180.4) euros), and the cost of reagents
      spent by the laboratory per patient (5.2 (IQR 5.2-6.4) versus 33.2 (IQR 2.3-34.2)
      euros). Thus, in the context of a clinical-biological partnership, the use of CRP
      in POCT present a practical and an economic interest.

PMID- 30226197
TI  - IgM Myeloma: case report and literature review.
AB  - The presence of serum monoclonal IgM is often associated with the diagnosis of
      Waldenstrom macroglobulinemia (WM) or other chronic lymphoproliferative
      disorders. IgM myeloma is a rare entity (0.5%). We report the case of an IgM
      myeloma complicated by systemic amyloidosis AL, with an impure nephrotic syndrome
      and a factor FX deficiency.

PMID- 30226198
TI  - 7e symposium " Biologie d'urgence et gaz du sang ".

PMID- 30226199
TI  - Pediatric Mercury Intoxication Mimicking Pheochromocytoma

PMID- 30226200
TI  - Switchable inteins for conditional protein splicing.
AB  - Synthetic biologists aim at engineering controllable biological parts such as
      DNA, RNA and proteins in order to steer biological activities using external
      inputs. Proteins can be controlled in several ways, for instance by regulating
      the expression of their encoding genes with small molecules or light. However,
      post-translationally modifying pre-existing proteins to regulate their function
      or localization leads to faster responses. Conditional splicing of internal
      protein domains, termed inteins, is an attractive methodology for this purpose.
      Here we discuss methods to control intein activity with a focus on those
      compatible with applications in living cells.

PMID- 30226201
TI  - A versatile perfusion bioreactor and endothelializable photo cross-linked tubes
      of gelatin methacryloyl as promising tools in tissue engineering.
AB  - Size and function of bioartificial tissue models are still limited due to the
      lack of blood vessels and dynamic perfusion for nutrient supply. In this study,
      we evaluated the use of cytocompatible methacryl-modified gelatin for the
      fabrication of a hydrogel-based tube by dip-coating and subsequent photo
      initiated cross-linking. The wall thickness of the tubes and the diameter were
      tuned by the degree of gelatin methacryl-modification and the number of dipping
      cycles. The dipping temperature of the gelatin solution was adjusted to achieve
      low viscous fluids of approximately 0.1 Pa s and was different for gelatin
      derivatives with different modification degrees. A versatile perfusion bioreactor
      for the supply of surrounding tissue models was developed, which can be adapted
      to several geometries and sizes of blood-vessel mimicking tubes. The manufactured
      bendable gelatin tubes were permeable for water and dissolved substances, like
      Nile Blue and serum albumin. As a proof of concept, human fibroblasts in a three
      dimensional collagen tissue model were successfully supplied with nutrients via
      the central gelatin tube under dynamic conditions for 2 days. Moreover, the tubes
      could be used as scaffolds to build-up a functional and viable endothelial layer.
      Hence, the presented tools can contribute to solving current challenges in tissue
      engineering.

PMID- 30226202
TI  - Evaluation of serum alkaline phosphatase measurement through the 4-year trueness
      verification program in China.
AB  - Background Alkaline phosphatase (ALP) is critical for various diseases. The
      International Federation of Clinical Chemistry and Laboratory Medicine had
      recommended the new reference procedure in 2011, but many manufacturers did not
      trace results to the higher procedure. Since 2012, the National Center for
      Clinical Laboratories (NCCL) in China has organized the trueness verification
      program (TV) with commutable materials. The present study summarizes the 4-year
      TV program to give an overview of the measurement standardization for ALP
      results. Methods Commutable serum-based materials with different concentrations
      were prepared and sent to participating laboratories. The target values were
      assigned by the reference lab network. Results The analytical performance was
      evaluated according to three indexes: trueness (bias), imprecision (CV) and
      accuracy (total error [TE]). The number of participating laboratories increased
      from 115 in 2012 to 287 in 2016. The pass rates of precision for homogeneous and
      heterogeneous systems were all above 85% over the 4 years; however, the pass
      rates of bias were much lower (<50%). Among the homogeneous systems, Roche
      Cobas/Modular had an obvious negative bias, whereas the mean positive bias for
      Beckman AU was prominent. As to the heterogeneous systems, the pass rates of bias
      for Sichuan Maccura (57.1%-78.6%) were higher than Roche Cobas/Modular (4.4%
      33.9%) and Beckman AU (35.7%-64.8%). Conclusions The PT/EQA program with
      commutable materials can be used to assess the trueness against target values
      assigned by reference procedures. For ALP, homogeneous systems did not perform
      better than heterogeneous systems. The bias for ALP performance was notable and
      was the main obstacle to its standardization in China.

PMID- 30226203
TI  - Is there a classical role for the clinical laboratory in digital health?
AB  - The classical role of the clinical laboratory, seen as the central place where
      the samples converge and from where the results are distributed, will be
      challenged by the development of digital health, the application of information
      technology (big data) and genomics to health care. When the development of
      disruptive new technologies will allow the production of accurate results outside
      the laboratory, its role will dramatically change. However, several factors are
      slowing down these evolutions. The quality of the existing data is relatively
      poor: lack of standardization of results, different units, different reference
      intervals, etc. The lab-on-a-chip technology is still relatively far from broad
      range application and the costs are higher than the traditional methods. There is
      the need for regulations of direct to consumer approaches that are posing big
      ethical problems. In the future, the clinical laboratory will maintain part of
      the "classical" role in the areas of research education and services. The large
      production will continue, favored by consolidation and reduction of the number of
      laboratories. The specialists of laboratory medicine have the task of
      collaborating with the national scientific societies and with the industry for
      improving harmonization of all the production phases, thus allowing the
      production of meaningful big data. Clinical laboratories have the role of
      implementing translational medicine. The new point-of-care (POC) technologies
      still need validation, the clinical laboratory is the place to do it. The
      advisory role toward clinicians and patients has to be improved, and a role in
      validating laboratory data interpretation apps and in controlling and supervising
      the functionality and the quality of the POC devices has to be developed.

PMID- 30226204
TI  - A comparison of complete blood count reference intervals in healthy elderly vs.
      younger Korean adults: a large population study.
AB  - Background The use of laboratory reference intervals based on younger populations
      is of questionable validity in older populations. We established reference
      intervals for 16 complete blood count (CBC) parameters in healthy elderly Koreans
      aged >=60 years and compared them to those of individuals aged 20-59 years.
      Methods Among 64,532 individuals (39,609 men and 24,923 women) aged >=20 years
      who underwent medical checkups, 8151 healthy subjects (12.6%, 5270 men and 2881
      women, including 675 and 511, respectively, who were >=60 years of age) were
      enrolled based on stringent criteria including laboratory, imaging and endoscopy
      results; previous medical history; and medication history. CBC parameters were
      measured using an Advia2120i instrument. Results Overall, healthy individuals
      aged >=60 years did not require separate reference intervals from those aged <60
      years except for red cell distribution width (RDW) and mean corpuscular
      hemoglobin (MCH) in women. However, subjects aged >=60 years still required sex
      specific reference intervals for red blood cell count, hemoglobin, hematocrit,
      MCH, monocytes and eosinophils. Separate reference intervals were required for
      MCH, eosinophils and basophils for certain age subgroups of men aged >=60 years,
      and for MCH and RDW in certain age subgroups of women aged >=60 years, compared
      to counterparts <60 years of age. Conclusions Healthy elderly Koreans can use the
      same reference intervals as younger populations. Thus, abnormal CBC results may
      not necessarily be attributable to physiologic changes but possible underlying
      diseases that should be investigated.

PMID- 30226205
TI  - Association of fibroblast growth factor 21 plasma levels with neonatal sepsis:
      preliminary results.

PMID- 30226206
TI  - Seasonality of month of birth in children and adolescents with autoimmune
      thyroiditis: a continuing conundrum.
AB  - Background The aim of this study was to analyze the seasonal birth month pattern
      in young patients with autoimmune thyroiditis and compare it with youth controls.
      Methods Medical records of a total of 298 children and adolescents of Greek
      origin, with a diagnosis of Hashimoto thyroiditis (HT) before the age of 21 years
      that were born from 1987 to 2010 were retrospectively reviewed. In addition, 298
      consecutive subjects that were born from 1988 to 2012 and evaluated in a tertiary
      unit for any reason, served as controls, provided that they had no personal or
      family history of thyroid or any other autoimmune disease. Results Significant
      differences were found between children and adolescents with HT and healthy
      controls in the yearly pattern of month of birth distribution (p=0.029). During
      month-by-month analysis, it was shown that the highest and lowest predispositions
      to HT were among those born in spring (March) (odds ratio [OR] 2.34, p=0.005),
      and autumn (November) (OR 0.49, p=0.035), respectively. A binary logistic
      regression model also revealed that season of birth and sex were the only factors
      that remained related to HT disease, even after adjustment for confounding
      factors such as year of birth and age (p<0.001, Nagelkerke r-square 0.151).
      Conclusions This study suggests that the effect of certain seasonal factors
      during fetal development, reflected by the seasonal differences in birth pattern,
      in children and adolescents with autoimmune thyroiditis could contribute to long
      term programming of an autoimmune response against the thyroid gland. Further
      studies are needed to demonstrate a clear cause and effect relationship between
      month of birth and HT.

PMID- 30226207
TI  - A case of Graves' disease associated with membranoproliferative
      glomerulonephritis and leukocytoclastic vasculitis.
AB  - Background The association of hyperthyroidism with renal disease is very rare and
      the importance of timely clinical recognition cannot be overemphasized. Case
      presentation An 11-year-old girl presented with gastrointestinal symptoms while
      hypertension, edema and abdominal pain were noticed on clinical examination.
      Laboratory investigation revealed: hemoglobin 9.4 (11.5-15.5) g/dL, total white
      cell count 16 (4.5-12)*109/L, platelets 247 (150-450)*109/L, C-reactive protein
      (CRP) 31.8 (<5) mg/L, blood urea nitrogen (BUN) 126 (13-43) mg/dL, creatinine
      0.98 (0.53-0.79) mg/dL, albumin 25 (35-52) g/dL, complement factor C3 0.7 (0.9
      1.8) g/L, complement factor C4 0.1 (0.1-0.4) g/L, tri-iodothyronine 6.5 (2.5-5.2)
      pg/mL, free thyroxine 2.4 (1-1.7) ng/dL, thyroid stimulating hormone (TSH) <0.02
      (0.5-4.3) mU/L. Urinalysis showed nephrotic range proteinuria. Renal function
      deteriorated necessitating hemodialysis (HD). A renal biopsy revealed an immune
      complex-mediated membranoproliferative glomerulonephritis (MPGN). Elevated
      thyroid hormones and suppressed TSH levels with elevated thyroperoxidase
      antibodies and thyroid stimulating immunoglobulins confirmed the diagnosis of
      Graves' disease. Corticosteroids were commenced and eventually thiamazole was
      added with gradual improvement of renal function, cessation of HD and discharge
      from the hospital. Conclusions Graves' disease complicated by MPGN is extremely
      rare, but can cause life-threatening complications.

PMID- 30226208
TI  - Adipocyte aquaporin 7 (AQP7) expression in lean children and children with
      obesity. Possible involvement in molecular mechanisms of childhood obesity.
AB  - Background Aquaporin 7 (AQP7), a water/glycerol transporting protein, regulates
      adipocyte glycerol efflux and influences lipid and glucose homeostasis. Altered
      AQP7 expression in adults leads to impaired glycerol dynamics, adipocyte
      hypertrophy and it predisposes them to obesity and diabetes. To assess its
      possible involvement in childhood obesity, this study investigated the expression
      of adipocyte AQP7 in cultured adipocytes of children. Methods Primary in vitro
      differentiated adipocyte cultures were developed from surgical biopsies of
      subcutaneous abdominal adipose tissue from 61 (46 prepubertal, 15 pubertal) lean
      children (body mass index [BMI] <85%) and 41 (22 prepubertal, 19 pubertal)
      children with obesity (BMI >95%). AQP7 expression was studied by reverse
      transcription polymerase chain reaction and Western immunoblotting and insulin by
      enzyme-linked immunosorbent assay. Results AQP7 messenger RNA (mRNA) was
      increased in the younger obese prepubertal (YOP) children but decreased in the
      obese adolescents (OA) (p=0.014) who also had increased insulin and homeostatic
      model assessment - insulin resistance (HOMA-IR). Lean pubertal (LP) children and
      YOP had increased 41 kDa AQP7 protein expression (p=0.001 and p=0.005,
      respectively). The OA who expressed 34 kDa AQP7 had lower triglyceride (TG)
      levels than those who did not express it (p=0.013). In the lean children, TG were
      negatively correlated with 34 kDa AQP7 (p=0.033). Conclusions The lower AQP7 mRNA
      expression in the OA may reflect a predisposition to adipocyte hypertrophy and
      metabolic dysfunction, as in the adults, whereas the YOP may be protected from
      this. The increased 41 kDa AQP7 protein expression in the LP may reflect the
      increased energy requirements of puberty for glycerol while in the YOP it may
      also be protective against the development of adipocyte hypertrophy.

PMID- 30226209
TI  - Vision impairment after traumatic brain injury: present knowledge and future
      directions.
AB  - Traumatic brain injury (TBI) is a major cause of mortality and morbidity in the
      USA as well as in the world. As a result of TBI, the visual system is also
      affected often causing complete or partial visual loss, which in turn affects the
      quality of life. It may also lead to ocular motor dysfunction, defective
      accommodation, and impaired visual perception. As a part of the therapeutic
      strategy, early rehabilitative optometric intervention is important. Orthoptic
      therapy, medication, stem cell therapy, motor and attention trainings are the
      available treatment options. Gene therapy is one of the most promising emerging
      strategies. Use of state-of-the-art nanomedicine approaches to deliver drug(s)
      and/or gene(s) might enhance the therapeutic efficacy of the present and future
      modalities. More research is needed in these fields to improve the outcome of
      this debilitating condition. This review focuses on different visual pathologies
      caused by TBI, advances in pre-clinical and clinical research, and available
      treatment options.

PMID- 30226210
TI  - Identifying pain in children with CHARGE syndrome.
AB  - Background and aims The objective was to conduct the first investigation to
      identify the frequency and intensity of pain experiences for individuals with
      CHARGE syndrome and to review the use of two established non-vocal pain
      assessments with children with CHARGE, the NCCPC-R (Non-Communicating Children's
      Pain Checklist-Revised) and the PPP (Pediatrics Pain Profile). Methods Parents of
      children with CHARGE were enrolled. Participants completed a pain questionnaire
      and the NCCPC-R and PPP twice, once for a baseline measure and second during a
      painful experience for their child. Results A moderate negative correlation
      between the mean intensity of pain and the mean duration of pain among
      individuals with CHARGE was found, rho=-0.34. There was a tendency for intensity
      of pain to increase for sources of pain that were of shorter duration. The NCCPC
      R and PPP were found to identify pain when compared to baseline performance (no
      pain) with a large effect, d=1.3. For the NCCPC-R, the difference between these
      ratings was significant beyond the 0.05 level, t (40)=8.15, p=0.000, 95% CI
      [16.93, 28.10]. Similarly, for the PPP, the mean pain ratings were significantly
      greater than the mean ratings for no pain, with significance beyond the 0.05
      level, t (51)=9.59, p=0.000, CI 95% [11.74, 17.96]. Conclusions Evidence exists
      that children with CHARGE experience pain. While the NCCPC-R and PPP were found
      to identify pain; future research should consider the development of a pain
      assessment individualized to pain behaviors present in CHARGE syndrome, given
      this population's unique expression of pain.

PMID- 30226211
TI  - The preanalytical phase in the era of high-throughput genetic testing. What the
      future holds.

PMID- 30226212
TI  - Estimation of blood and bone marrow doses of thyroid carcinoma patients treated
      with 131I through gamma spectrometry.
AB  - 131I therapy is the treatment for patients with differentiated thyroid carcinoma
      (DTC) to ablate remnant thyroid tissue after surgery. The aim of this study was
      to estimate the absorbed doses to the blood and bone marrow of patients with DTC
      using gamma spectrometry. The evaluation of the absorbed dose in blood and bone
      marrow is a good indicator of a patient's response and its radiological
      protection. The average of low activities administered (AAAL) to ten patients was
      3.20 GBq and the average of high activities administered (AAAH) to eight patients
      was 4.95 GBq. The blood and bone marrow doses were determined according to
      Lassmann et al 2008, performing successive measurements of activity in blood
      samples and whole body. Blood samples of 2 ml were taken during the first 48 h;
      the first one was extracted 2 h after the administration of the capsule and the
      following ones were taken every 12 h. The whole-body measurements were made at
      regular intervals of time throughout the patient's isolation period using a
      mobile gamma spectrometry system located inside the isolation room of the Dr
      Hernan Henriquez Aravena Hospital. The average residence times in blood and whole
      body were (6.9 +/- 1.7) * 10-4 h ml-1 and (23.2 +/- 4.5) h, respectively. The
      average doses in blood and bone marrow of patients with AAAL were (0.33 +/- 0.09)
      Gy and (0.63 +/- 0.18) Gy, respectively, and with AAAH were (0.48 +/- 0.06) Gy
      and (0.87 +/- 0.19) Gy, respectively. In all studied patients, the bone marrow
      doses were less than 2 Gy. The results were compared with the previously
      published values, finding some differences between the residence times and
      significant differences in the doses, which show the need to compare the
      different methodologies.

PMID- 30226213
TI  - Geometric effect on quantum anomalous Hall states in magnetic topological
      insulators.
AB  - An intriguing observation on the quantum anomalous Hall effect (QAHE) in magnetic
      topological insulators (MTIs) is the dissipative edge states, where quantized
      Hall resistance is accompanied by nonzero longitudinal resistance. We numerically
      investigate this dissipative behavior of QAHE in MTIs with a three-dimensional
      tight-binding model and non-equilibrium Green's function formalism. It is found
      that, in clean samples, the geometric mismatch between the detecting electrodes
      and the MTI sample leads to additional scattering in the central Hall bar, which
      is similar to the effect of splitting gates in the traditional Hall effect. As a
      result, while the Hall resistance remains quantized, the longitudinal resistance
      deviates from zero due to such additional scattering. It is also shown that
      external magnetic fields as well as disorder scattering can suppress the
      dissipation of the longitudinal resistance. These results are in good agreement
      with previous experimental observations and provide insight on the fabrication of
      QAHE devices.

PMID- 30226214
TI  - Evaluation of robot-assisted MRI-guided prostate biopsy: needle path analysis
      during clinical trials.
AB  - While the interaction between a needle and the surrounding tissue is known to
      cause a significant targeting error in prostate biopsy leading to false-negative
      results, few studies have demonstrated how it impacts in the actual procedure. We
      performed a pilot study on robot-assisted MRI-guided prostate biopsy with an
      emphasis on the in-depth analysis of the needle-tissue interaction in vivo. The
      data were acquired during in-bore transperineal prostate biopsies in patients
      using a 4 degrees-of-freedom (DoF) MRI-compatible robot. The anatomical
      structures in the pelvic area and the needle path were reconstructed from MR
      images, and quantitatively analyzed. We analyzed each structure individually and
      also proposed a mathematical model to investigate the influence of those
      structures in the targeting error using the mixed-model regression. The median
      targeting error in 188 insertions (27 patients) was 6.3 mm. Both the individual
      anatomical structure analysis and the mixed-model analysis showed that the
      deviation resulted from the contact between the needle and the skin as the main
      source of error. On contrary, needle bending inside the tissue (expressed as
      needle curvature) did not vary among insertions with targeting errors above and
      below the average. The analysis indicated that insertions crossing the
      bulbospongiosus presented a targeting error lower than the average. The mixed
      model analysis demonstrated that the distance between the needle guide and the
      patient skin, the deviation at the entry point, and the path length inside the
      pelvic diaphragm had a statistically significant contribution to the targeting
      error (p  <  0.05). Our results indicate that the errors associated with the
      elastic contact between the needle and the skin were more prominent than the
      needle bending along the insertion. Our findings will help to improve the
      preoperative planning of transperineal prostate biopsies.

PMID- 30226215
TI  - Magnetic impurity in topological nodal loop semimetals.
AB  - We investigate the Kondo effect of a spin-1/2 magnetic impurity in a topological
      nodal loop semimetal, in which band touchings form a nodal loop. The Fermi
      surface of a nodal loop semimetal is a torus or a drum-like structure, which is
      determined by chemical potential. When the chemical potential MU lies at the
      nodal loop ([Formula: see text]), the magnetic impurity and the conduction
      electrons form bound states only if their coupling exceeds a critical value. As
      the chemical potential is tuned away from the nodal loop, the Fermi surface
      becomes a torus or drum-like structure and the impurity and the host material
      always favor a bound state due to the finite density of state. Due to the
      anisotropic dispersion relationship in the energy band, the spatial spin-spin
      correlations [Formula: see text]([Formula: see text]) are of power-law decay with
      the decay rates proportional to [Formula: see text] and [Formula: see text] in
      different directions, respectively. The product [Formula: see text] and [Formula:
      see text] oscillates in coordinate space and the period is enhanced gradually as
      the Fermi surface evolves from a torus surface into a drum-like structure.

PMID- 30226216
TI  - Thrust force characterization of free-swimming soft robotic jellyfish.
AB  - Five unique soft robotic jellyfish were manufactured with eight pneumatic network
      tentacle actuators extending radially from their centers. These jellyfish robots
      were able to freely swim untethered in the ocean, to steer from side to side, and
      to swim through orifices more narrow than the nominal diameter of the jellyfish.
      Each of the five jellyfish robots were manufactured with a different composition
      of body and tentacle actuator Shore hardness. A three-factor study was performed
      with these five jellyfish robots to determine the impact that actuator material
      Shore hardness, actuation frequency, and tentacle stroke actuation amplitude had
      upon the measured thrust force. It was found that all three of these factors
      significantly impacted mean thrust force generation, which peaked with a half
      stroke actuation amplitude at a frequency of 0.8 Hz.

PMID- 30226217
TI  - G protein-coupled receptor kinase 2 inhibition improves erectile function through
      amelioration of endothelial dysfunction and oxidative stress in a rat model of
      type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) is a common cause of erectile dysfunction (ED).
      It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2)
      overexpression contributes to diabetic endothelial dysfunction and oxidative
      stress, which also underlies ED in T2DM. We hypothesized that GRK2 overexpressed
      and attenuated endothelial function of the cavernosal tissue in a rat model of
      T2DM. T2DM rats were established by feeding with a high-fat diet (HFD) for 2
      weeks and then administering two intraperitoneal (IP) injections of a low dose of
      streptozotocin (STZ), followed by continuous feeding with a HFD for 6 weeks. GRK2
      was inhibited by IP injection of paroxetine, a selective GRK2 inhibitor, after
      STZ injection. Insulin challenge tests, intracavernous pressure (ICP), GRK2
      expression, the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS)
      pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit
      gp91phox, nitric oxide (NO), reactive oxygen species (ROS) production, and
      apoptosis in cavernosal tissue were examined. Less response to insulin injection
      was observed in T2DM rats 2 weeks after HFD. Markedly increased GRK2 expression,
      along with impaired Akt/eNOS pathway, reduced NO production, increased gp91phox
      expression and ROS generation, increased apoptosis and impaired erectile function
      were found in T2DM rats. Inhibition of GRK2 with paroxetine ameliorated Akt/eNOS
      signaling, restored NO production, downregulated NADPH oxidase, subsequently
      inhibited ROS generation and apoptosis, and ultimately preserved erectile
      function. These results indicated that GRK2 upregulation may be an important
      mechanism underlying T2DM ED, and GRK2 inhibition may be a potential therapeutic
      strategy for T2DM ED.

PMID- 30226218
TI  - Protein supplementation intake for bodybuilding and resistance training may
      impact sperm quality of subfertile men undergoing fertility treatment: a pilot
      study.

PMID- 30226219
TI  - Natural Transmission of b2/b3 Subdeletion or Duplication to Expanded Y Chromosome
      Microdeletions.
AB  - BACKGROUND Y chromosome microdeletions are usually de novo mutations, but in
      several cases, transmission from fertile fathers to infertile sons has been
      reported. MATERIAL AND METHODS We report 3 cases of infertile patients who
      inherited expanded Y chromosome microdeletions from their fathers, who carried
      b2/b3 subdeletion or duplication. The karyotype was analyzed using G-banding.
      High-throughput sequencing was used to detect AZF region microdeletions. RESULTS
      Cytogenetic analysis showed a normal karyotype 46,XY in patient 1 (P1), patient 2
      (P2), and their fathers (F1 and F2). Patient 3 (P3) and his father (F3) presented
      a karyotype of 46,XY,Yqh-. High-throughput sequencing for the AZF disclosed an
      identical b2/b3 subdeletion in the F1 and F2. P1 had an AZFc deletion that
      accounted for 3.5 Mb, and P2 had an AZFa+b+c microdeletion that accounted for
      10.5 Mb. F3 had a b2/b3 duplication of 1.8Mb, but P3 had an AZFb+c deletion of
      6.2 Mb. CONCLUSIONS Our findings suggest that b2/b3 partial deletion or
      duplication can lead to structural instability in the Y chromosome and be a risk
      factor of complete deletion of AZFc or more expanded deletion during
      transmission.

PMID- 30226220
TI  - Response to comment on 'Hydrogen bonds in crystalline d-alanine: diffraction and
      spectroscopic evidence for differences between enantiomers'.
AB  - A response is given to comments by Burgi & Macchi [IUCrJ (2018), 5, 654-657]
      about Belo et al. [IUCrJ (2018), 5, 6-12.].

PMID- 30226223
TI  - Synthesis and properties of isoindigo and benzo[1,2-b:4,5-b']bis[b]benzothiophene
      oligomers.
AB  - A well-defined series of long and soluble isoindigo thienoacene oligomers have
      been synthesized from a novel electron deficient building block: benzo[1,2-b:4,5
      b']bis[b]benzothiophene bislactams. Extension of the pi-conjugated systems
      facilitates control of the optical, electronic and device characteristics.

PMID- 30226229
TI  - Quantum tunneling dynamical behaviour on weakly bound complexes: the case of a
      CO2-N2 dimer.
AB  - Quantum tunneling is a common fundamental quantum mechanical phenomenon. The
      dynamics induced by this effect is closely connected to the shape of the
      potentials. Here we treat the CO2-N2 van der Waals complex dynamics using a first
      principles treatment where nuclear motions and nuclear spins are fully
      considered. This dimer is found to exhibit complex spectral and dynamical
      features that cannot be accounted for using standard experimental and theoretical
      models. We shed light on some aspects of its quantum tunneling dynamics that
      remained unexplained since its first evidence 85 years ago. CO2-N2 represents
      also an important prototype for studying the systematic (as in NH3) lifting of
      degeneracy due to tunneling effects and large amplitude motions. Vibrational
      memory and quantum localization effects are evidenced. Plural potential wells
      separated by potential barriers are commonly found for polyatomic organic and
      inorganic molecules (e.g., cis-trans isomerization and enol-keto tautomerism).
      The present findings are useful for understanding the complex quantum effects
      that may occur there.

PMID- 30226230
TI  - Effect of nano-pillared surfaces with an arrangement density gradient on droplet
      coalescence dynamics.
AB  - The ability to predict and control the coalescence of droplets is of great
      importance for both industrial and technological applications, including 3D
      printing, micro-cladding, and self-assembly. Here, a textured surface decorated
      with nano-pillared arrays was designed and its arrangement density (f) was found
      to significantly affect the coalescence dynamics of droplets through changing
      their wettability. A large arrangement density f of the nano-pillared arrays
      would induce a Cassie wetting state for droplets, which supports the coalescence
      process. But when decreasing f to a value that produces a Wenzel wetting state,
      the coalescence is heavily impeded by the nano-pillars. However, a very small
      arrangement density f is also favorable for coalescence because the pinning
      effect resulting from the nano-pillars becomes ignored. More importantly, special
      substrates were well designed by nano-pillars with a density gradient in order to
      control the coalescence dynamics for some potential applications. This work helps
      to shed light on the coalescence dynamics of droplets on a microtextured surface
      modified with different arranged nano-pillars and thereby provides guidance on
      how to control their behaviors.

PMID- 30226231
TI  - Suppressing charge recombination in small-molecule ternary organic solar cells by
      modulating donor-acceptor interfacial arrangements.
AB  - The ternary blending strategy has been a widely used method to achieve high
      performance in organic photovoltaics. However, the impact of the third component
      on the donor-acceptor interface geometries is still unclear, especially with
      regard to the microscopic structures in the mixed regions. In this study, we have
      investigated the donor-acceptor molecular packing structures in the mixed region
      as well as the exciton dissociation and charge recombination properties in all
      small-molecule ternary solar cells based on the new DR3TBDTT:DR3TBDTT-E:PC71BM
      system by means of molecular dynamics simulations combined with electronic
      structure calculations. The simulated results reveal that the incorporation of
      10% DR3TBDTT-E in the ternary blend can lead to a decrease in the probability of
      finding PC71BM close to the central electron-donating benzodithiophene moiety,
      and thus this can reduce the binding energy of the lowest charge-transfer state
      and the electronic coupling of charge recombination. However, with a further
      increase of the doping ratio, PC71BM aggregation becomes weak, which is harmful
      to electron transport. Therefore, superior performance can be only obtained with
      a proper amount of the third component for ternary blend solar cells.

PMID- 30226232
TI  - Mid-infrared absorption of trapped electrons in titanium(iv) oxide particles
      using a photoacoustic FTIR technique.
AB  - Mid-infrared absorption of titanium(iv) oxide (TiO2) under ultraviolet (UV)
      irradiation was studied by Fourier transform infrared spectroscopy using a
      photoacoustic (PA) technique. UV irradiation induced an upward shift of the PA
      spectra, which is due to the trivalent titanium (Ti3+) species produced by
      electron accumulation. The PA spectra under UV irradiation mainly depend on the
      crystal structure, indicating that the energy levels of Ti3+ are largely
      determined by crystal structures.

PMID- 30226234
TI  - Narrowing the gap between experimental and computational determination of methyl
      group dynamics in proteins.
AB  - Nuclear magnetic resonance (NMR) spin relaxation has become the mainstay
      technique to sample protein dynamics at atomic resolution, expanding its
      repertoire from backbone 15N to side-chain 2H probes. At the same time, molecular
      dynamics (MD) simulations have become increasingly powerful to study protein
      dynamics due to steady improvements of physical models, algorithms, and
      computational power. Good agreement between generalized Lipari-Szabo order
      parameters derived from experiment and MD simulation has been observed for the
      backbone dynamics of a number of proteins. However, the agreement for the more
      dynamic side-chains, as probed by methyl group relaxation, was much worse. Here,
      we use T4 lysozyme (T4L), a protein with moderate tumbling anisotropy, to
      showcase a number of improvements that reduce this gap by a combined evaluation
      of NMR relaxation experiments and MD simulations. By applying a protein force
      field with accurate methyl group rotation barriers in combination with a
      solvation model that yields correct protein rotational diffusion times, we find
      that properly accounting for anisotropic protein tumbling is an important factor
      to improve the match between NMR and MD in terms of methyl axis order parameters,
      spectral densities, and relaxation rates. The best agreement with the
      experimentally measured relaxation rates is obtained by a posteriori fitting the
      appropriate internal time correlation functions, truncated by anisotropic overall
      tumbling. In addition, MD simulations led us to account for a hitherto unrealized
      artifact in deuterium relaxation experiments arising from strong coupling for
      leucine residues in uniformly 13C-enriched proteins. For T4L, the improved
      analysis reduced the RMSD between MD and NMR derived methyl axis order parameters
      from 0.19 to 0.11. At the level of the spectral density functions, the
      improvements allow us to extract the most accurate parameters that describe
      protein side-chain dynamics. Further improvement is challenging not only due to
      force field and sampling limitations in MD, but also due to inherent limitations
      of the Lipari-Szabo model to capture complex dynamics.

PMID- 30226235
TI  - Electrical property and Schottky behavior of a flexible Schiff-base compound: X
      ray structure and stabilization of 1D water chain.
AB  - The flexible Schiff-base compound 2,2'-((1,4-phenylenebis
      (methylene))bis(sulfanediyl))bis(N-(pyridin-4-ylmethylene)aniline) (1; pbbpa) has
      been synthesized by a two-step synthetic procedure and characterized by elemental
      analysis, infrared (IR) spectroscopy, powder X-ray diffraction (PXRD) pattern and
      single crystal X-ray diffraction (SCXRD) technique. The compound exhibits
      electrical conductivity in the semiconducting region, as revealed by band gap
      calculation and further confirmed by density functional theory (DFT)
      computations. Interestingly, the compound formed a Schottky interface with
      aluminum (Al) metal, which is supported by the impedance spectroscopy (IS)-based
      network analysis. Besides, SCXRD of compound 1 reveals the formation of a one
      dimensional (1D) water chain encapsulated by the hydrogen bonded supramolecular
      network.

PMID- 30226238
TI  - Two-photon chiro-optical properties of gold Au25 nanoclusters.
AB  - Atomically-precise chiral gold nanoclusters hold promise for an accurate
      manipulation of chiro-optical properties, both in linear and nonlinear optics
      regimes. Here, we present the determination of two-photon linear-circular
      dichroism and two-photon circular dichroism (TPCD) of Au25[(Capt)18]- (where Capt
      is captopril). TPCD is found to be two orders of magnitude higher than one-photon
      circular dichroism.

PMID- 30226239
TI  - Surface plasmon modes of nanomesh-on-mirror nanocavities prepared by nanosphere
      lithography.
AB  - Metal-insulator-metal (MIM) structures show great potential for numerous photonic
      applications due to their ability to confine light energy to volumes with deeply
      sub-wavelength dimensions. Here, MIM structures comprising hexagonal gold
      nanohole arrays were prepared by nanosphere lithography. Angle-resolved UV-vis
      NIR spectroscopy revealed a series of narrow, dispersive and non-dispersive
      modes, which were attributed to the excitation of surface plasmon polariton (SPP)
      modes. Applying finite-difference time-domain (FDTD) simulations and analytical
      diffraction phase-matching theory all resonances can be ascribed to only two SPP
      modes traveling at the outer gold surface and in the gap layer sandwiched between
      two metal films. Metamaterial resonances, as reported in the literature for
      similar structures, are not needed to fully explain the reflectance spectra.
      Bragg scattering of the symmetric gap SPP mode results in a gap resonance, which
      is insensitive to the angle of incidence over a broad angular range. The spectral
      position of this flat band can be controlled by tuning the grating period of the
      nanohole array as well as the thickness and the refractive index of the
      dielectric gap.

PMID- 30226240
TI  - Targeting myeloid regulators by paclitaxel-loaded enzymatically degradable
      nanocups.
AB  - Tumor microenvironment is characterized by immunosuppressive mechanisms
      associated with the accumulation of immune regulatory cells - myeloid-derived
      suppressor cells (MDSC). Therapeutic depletion of MDSC has been associated with
      inhibition of tumor growth and therefore represents an attractive approach to
      cancer immunotherapy. MDSC in cancer are characterized by enhanced enzymatic
      capacity to generate reactive oxygen and nitrogen species (RONS) which have been
      shown to effectively degrade carbonaceous materials. We prepared enzymatically
      openable nitrogen-doped carbon nanotube cups (NCNC) corked with gold
      nanoparticles and loaded with paclitaxel as a therapeutic cargo. Loading and
      release of paclitaxel was confirmed through electron microscopy, Raman
      spectroscopy and LC-MS analysis. Under the assumption that RONS generated by
      MDSCs can be utilized as a dual targeting and oxidative degradation mechanism for
      NCNC, here we report that systemic administration of paclitaxel loaded NCNC
      delivers paclitaxel to circulating and lymphoid tissue MDSC resulting in the
      inhibition of growth of tumors (B16 melanoma cells inoculated into C57BL/6 mice)
      in vivo. Tumor growth inhibition was associated with decreased MDSC accumulation
      quantified by flow cytometry that correlated with bio-distribution of gold-corked
      NCNC resolved by ICP-MS detection of residual gold in mouse tissue. Thus, we
      developed a novel immunotherapeutic approach based on unique nanodelivery
      vehicles, which can be loaded with therapeutic agents that are released
      specifically in MDSC via NCNC selective enzymatic "opening" affecting change in
      the tumor microenvironment.

PMID- 30226241
TI  - A chemiresistive sensor array from conductive polymer nanowires fabricated by
      nanoscale soft lithography.
AB  - One-dimensional organic nanostructures are essential building blocks for high
      performance gas sensors. Constructing an e-nose type sensor array is the current
      golden standard in developing portable systems for the detection of gas mixtures.
      However, facile fabrication of nanoscale sensor arrays is still challenging due
      to the high cost of the conventional nanofabrication techniques. In this work, we
      fabricate a chemiresistive gas sensor array composed of well-ordered sub-100 nm
      wide conducting polymer nanowires using cost-effective nanoscale soft
      lithography. Poly(3,4-ethylene-dioxythiophene)-poly(styrene sulfonate)
      (PEDOT:PSS) nanowires functionalized with different self-assembled monolayers
      (SAMs) are capable of identifying volatile organic compounds (VOCs) at a low
      concentration range. The side chains and functional groups of the SAMs introduce
      different sensitivities and selectivities to the targeted analytes. The distinct
      response pattern of each chemical is subjected to pattern recognition protocols,
      which leads to a clear separation towards ten VOCs, including ketones, alcohols,
      alkanes, aromatics and amines. These results of the chemiresistive gas sensor
      array demonstrate that nanoscale soft lithography is a reliable approach for
      fabricating nanoscale devices and has the potential of mass producibility.

PMID- 30226242
TI  - Self-sensitization induced upconversion of Er3+ in core-shell nanoparticles.
AB  - A mechanistic study of upconversion from lanthanides is of great importance for
      the fundamental research of upconversion materials and their diverse frontier
      applications. However, the most efficient upconversion of lanthanides is still
      obtained in a commonly used sensitizer-activator coupled system. Here we report a
      mechanistic investigation on the upconversion of Er3+ through self-sensitization
      which is applicable for 808, 980 and 1530 nm excitations. It is found that the
      cooperative energy transfer upconversion followed by cross-relaxation occurring
      among Er3+ ions plays a critical role in producing and enhancing the red
      upconversion for the samples with high dopant concentrations (e.g., >20 mol%).
      The red upconversion color can be further purified and enhanced by mediating the
      upconversion dynamics through introducing the lanthanides of Ho3+, Tm3+ and Yb3+,
      which can effectively contribute to the population in the red emitting state.
      Moreover, the energy migration in the Er-sublattice was also found to be a
      possible origin for quenching upconversion, which was proved and effectively
      suppressed by designing a tri-layered nanostructure where the distribution of
      Er3+ is spatially controllable. Our results gain access into the insight of
      upconversion dynamics in self-sensitization induced upconversion which would help
      the search for other new kinds of upconversion materials.

PMID- 30226243
TI  - A bottom-up process of self-formation of highly conductive titanium oxide (TiO)
      nanowires on reduced SrTiO3.
AB  - Reduced titanium oxide structures are regarded as promising materials for various
      catalytic and optoelectronic applications. There is thus an urgent need for
      developing methods of controllable formation of crystalline nanostructures with
      tunable oxygen nonstoichiometry. We introduce the Extremely Low Oxygen Partial
      Pressure (ELOP) method, employing an oxygen getter in close vicinity to an oxide
      during thermal reduction under vacuum, as an effective bottom-up method for the
      production of nanowires arranged in a nanoscale metallic network on a SrTiO3
      perovskite surface. We demonstrate that the TiO nanowires crystallize in a highly
      ordered cubic phase, where single nanowires are aligned along the main
      crystallographic directions of the SrTiO3 substrate. The dimensions of the
      nanostructures are easily tunable from single nanometers up to the mesoscopic
      range by varying the temperature of reduction. The interface between TiO and
      SrTiO3 (metal and insulator) was found to be atomically sharp providing the
      unique possibility of the investigation of electronic states, especially since
      the high conductivity of the TiO nanostructures is maintained after room
      temperature oxidation. According to the growth model we propose, TiO nanowire
      formation is possible due to the incongruent sublimation of strontium and
      crystallographic shearing, triggered by the extremely low oxygen partial pressure
      (ELOP). The controlled formation of conductive nanowires on a perovskite surface
      holds technological potential for implementation in memristive devices, organic
      electronics, or for catalytic applications, and provides insight into the
      mechanism of nanoscale phase transformations in metal oxides. We believe that the
      ELOP mechanism of suboxide formation is suitable for the formation of reduced
      suboxides on other perovskite oxides and for the broader class of transition
      metal oxides.

PMID- 30226245
TI  - Accurate and sensitive single-cell-level detection of copy number variations by
      micro-channel multiple displacement amplification (MUcMDA).
AB  - Whole genome amplification (WGA) has laid the foundation for investigating
      complex genomic alteration with single-cell or even single-molecule resolution.
      Coupled with sequencing-based copy number variation (CNV) analysis, it promotes
      understanding of the nature of commonly existing genetic heterogeneity by
      constructing the sequencing profiles for every single cell. However, prevailing
      methods only provide insights into limited aspects due to their intrinsic
      technical challenges. Their output data, as a result, fails to render
      comprehensive information (which is) concerned. Here, we describe the CNV
      detection analysis based on micro-channel multiple displacement amplification
      (MUcMDA), a protocol able to provide optimized amplification uniformity while
      inheriting the advantages of MDA chemistry. We demonstrate the analysis of both
      the normal diploid YH-1 cell line and the aneuploid K562 cancer cell line. In the
      detection of simulated CNVs ranging from 300 kb to 2 Mb, MUcMDA can respectively
      increase the detection rates of copy number loss and gain by 28.8% and 40.2% on
      average, using only 0.2* sequencing data. When detecting the inherent CNVs in
      tumor cells, the resolution of CNV recognition can be improved to 250 kb.
      Starting from either superabundant template copies or minute single-cell-level
      input, this easily accessible approach is capable of providing quantitatively
      reliable coverage as well as more robust GC-content regression for CNV detection.

PMID- 30226246
TI  - "Transformed" Fe3S4 tetragonal nanosheets: a high-efficiency and body-clearable
      agent for magnetic resonance imaging guided photothermal and chemodynamic
      synergistic therapy.
AB  - To retain the agents in tumors for cancer diagnosis and therapy, and then to
      remove them from the body, are key for the clinical applications of ideal
      inorganic theranostic agents. To meet these needs, we have developed a
      transformed theranostic platform, employing PVP coated Fe3S4 tetragonal
      nanosheets (TNSs), which could effectively accumulate in the tumor under magnetic
      targeting, whilst gradually transforming to small particles (~5 nm) over three
      weeks. These were then effectively excreted from the body in normal physiological
      conditions after exerting their therapeutic effect. The aqueous dispersion of PVP
      coated Fe3S4 TNSs had an intense near-infrared absorption, excellent photothermal
      conversion efficiency (64.3%) and great T2 weighted magnetic resonance imaging
      properties (71.3 mM-1 S-1). In addition, Fe3S4 TNSs could realize a synergistic
      photothermal therapy (PTT)/chemodynamic therapy (CDT), because the localized heat
      produced by PTT from the defect-rich structure could enhance the Fenton process
      by utilizing the overproduced H2O2 in the tumor microenvironment, and in return,
      the produced OH could inhibit tumor growth and recurrence after PPT. We thus
      developed a high-efficiency inorganic theranostic platform which was effectively
      cleared from the body. This will open up a new avenue for the design of inorganic
      agents for clinical applications in the future.

PMID- 30226247
TI  - Homodimerization driven self-assembly of glycoluril molecular clips with
      covalently immobilized poly(epsilon-caprolactone).
AB  - We present an unexpected self-assembly of a glycoluril clip-poly(epsilon
      caprolactone) conjugate in chloroform. The conjugate forms homodimer aggregates
      due to supramolecular interactions between glycoluril moieties, which was
      confirmed with MALDI-TOF-ms and 1H NMR. TEM revealed the formation of
      multilayered nanosized prism-shaped objects resembling tree bark in nature.

PMID- 30226248
TI  - Energy conversion at nanointerfaces: general discussion.

PMID- 30226250
TI  - Phosphine oxide-based tricarbonylrhenium(i) complexes from phosphine/phosphine
      oxide and dihydroxybenzoquinones.
AB  - Neutral phosphine oxide (P[double bond, length as m-dash]O) donor-based
      organometallic complexes [{Re(CO)3O[double bond, length as m-dash]PCy3}{MU
      DHBQ}{Re(CO)3O[double bond, length as m-dash]PCy3}] (1), [{Re(CO)3O[double bond,
      length as m-dash]PPh3}{MU-DHBQ}{Re(CO)3O[double bond, length as m-dash]PPh3}]
      (2), [{Re(CO)3O[double bond, length as m-dash]PCy3}{MU-THQ}{Re(CO)3O[double bond,
      length as m-dash]PCy3}] (3), [{Re(CO)3O[double bond, length as m-dash]PPh3}{MU
      THQ}{Re(CO)3O[double bond, length as m-dash]PPh3}] (4), [{Re(CO)3O[double bond,
      length as m-dash]PCy3}{MU-CA}{Re(CO)3O[double bond, length as m-dash]PCy3}] (5),
      and [{Re(CO)3O[double bond, length as m-dash]PPh3}{MU-CA}{Re(CO)3O[double bond,
      length as m-dash]PPh3}] (6) were assembled from phosphine/phosphine oxide, a
      dihydroxybenzoquinone donor and Re2(CO)10via a one-pot solvothermal approach. The
      soft phosphine donor was transformed into a hard phosphine oxide donor during the
      formation of 1, 3, 4, 5, and 6. The complexes 1-6 were air and moisture stable
      and were soluble in polar organic solvents. The complexes were characterized by
      elemental analysis, FT-IR, and NMR spectroscopic methods. The molecular
      structures of 1, 2, 4, and 6 were analyzed by single-crystal X-ray diffraction
      analysis. The UV-Visible absorption studies indicated that 1-6 in THF display
      strong visible light absorption in the range of ~350-700 nm.

PMID- 30226251
TI  - Syntheses of the plant auxin conjugate 2-O-(indole-3-acetyl)-myo-inositol IAInos.
AB  - The plant hormone conjugate 2-O-(indole-3-acetyl)-myo-inositol (IAInos) has been
      selectively prepared for the first time by two routes from myo-inositol. One of
      the syntheses depended upon the construction of the 3-indoleacetyl group by a
      Fischer indole synthesis on an unreactive axial hydroxyl group, while the other
      via a direct acylation of the equatorially orientated hydroxy group created by
      conformational constraint of the cyclohexane ring. The latter synthesis produced
      IAInos in 5 steps and 29% overall yield.

PMID- 30226252
TI  - The role of mechanical force on the kinetics and dynamics of electrochemical
      redox reactions on graphene.
AB  - Electrochemical reactions are a critical class of processes strongly influenced
      by atomic scale effects, where the relationships between local chemical
      composition, stress, strain, and reactivity are not well understood. Here we
      investigate the relationship between applied stress and reaction rates for the
      oxygen evolution reaction on multi-layered graphene using conductive atomic force
      microscopy. During the reaction, oxygen groups accumulate on the surface and the
      oxygenation rate increases with applied load. The results also show that the rate
      is not uniform across the surface, where local edges and defects are more
      reactive than the basal plane. The results presented here are interpreted in the
      context of transition state theory, where applied load over the reaction
      coordinate linearly modifies the energy landscape. This work motivates the
      general efficacy of atomic force microscopy as a tool to study relationships
      between local mechanical surface effects and electrochemical reactivity.

PMID- 30226253
TI  - Metal-organic framework derived leaf-like CoSNC nanocomposites for supercapacitor
      electrodes.
AB  - The designed construction of micro-/nano-structures and multi-composites on
      electrodes showed a promising prospect to improve electrochemical properties in
      supercapacitors. Herein, a facile carbonizing strategy was adopted for
      fabricating leaf-like CoSNC nanocomposites, which possess both the sheet
      structure and multi-composites of well-dispersed CoS2 nanoparticles in N-doped
      carbon frameworks. First, the leaf-like nanocomposites with high aspect ratios
      effectively shortened the ion/electron transmission paths and exposed more
      faradaic redox sites. Second, the N-doped carbon frameworks could stabilize the
      electrode structure during charge/discharge processes. Third, the well-dispersed
      CoS2 nanoparticles could also enhance the electrochemical kinetics. Hence, leaf
      like CoSNC nanocomposites as electrode materials exhibited high specific
      capacitance, good rate capacity and cycling stability.

PMID- 30226254
TI  - OPGs: promising anode materials with high specific capacity and rate capability
      for Li/Na ion batteries.
AB  - Two-dimensional (2D) nanostructures with high specific capacity and high rate
      capability have attracted extensive attention due to their promising applications
      as anode materials for rechargeable ion batteries. In this study, we have
      employed density functional theory calculations to explore the electrochemical
      properties of Li and Na atoms, adsorption and diffusion on 2D carbon nanosheets
      named Octagon-Pentagon-Graphenes (OPGs). Two types of OPGs are considered, i.e.
      OPG_L and OPG_Z, and were found to be stable with much lower binding energies
      than that of graphdiyne. Both the nanosheets can combine Li/Na atoms strongly and
      easily. In the OPG_L, low energy barriers of 0.292 and 0.265 eV are obtained for
      the diffusion of Li and Na atoms, while in the OPG_Z, these barriers are much
      smaller. At room temperature, the diffusion rate of a Li atom on the OPGs is
      estimated to be at least 10 times faster than that on graphene. An ultrahigh
      Li/Na storage capacity of 2230 mA h g-1 can be achieved in both the OPG_L and
      OPG_Z, which is about 6 times larger than the 372 mAh g-1 of graphene. During the
      whole processes of Li/Na ion insertion, the OPGs exhibit a low average operating
      voltage and good metallic properties. Our results suggest that high specific
      capacity and rate capability could be expected in OPG-based Li/Na ion batteries.

PMID- 30226255
TI  - Supported lipid bilayers with encapsulated quantum dots (QDs) via liposome
      fusion: effect of QD size on bilayer formation and structure.
AB  - Understanding interactions between functional nanoparticles and lipid bilayers is
      important to many emerging biomedical and bioanalytical applications. In this
      paper, we report incorporation of hydrophobic cadmium sulphide quantum dots (CdS
      QDs) into mixed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) liposomes, and into
      their supported bilayers (SLBs). The QDs were found embedded in the hydrophobic
      regions of the liposomes and the supported bilayers, which retained the QD
      fluorescent properties. In particular, we studied the effect of the QD size (2.7
      5.4 nm in diameter) on the formation kinetics and structure of the supported
      POPC/POPE bilayers, monitored in situ using quartz crystal microbalance with
      dissipation monitoring (QCM-D), as the liposomes ruptured onto the substrate. The
      morphology of the obtained QD-lipid hybrid bilayers was studied using atomic
      force microscopy (AFM), and their structure by synchrotron X-ray reflectivity
      (XRR). It was shown that the incorporation of hydrophobic QDs promoted bilayer
      formation on the PEI cushion, evident from the rupture and fusion of the QD
      endowed liposomes at a lower surface coverage compared to the liposomes without
      QDs. Furthermore, the degree of disruption in the supported bilayer structure
      caused by the QDs was found to be correlated with the QD size. Our results
      provide mechanistic insights into the kinetics of the rupturing and formation
      process of QD-endowed supported lipid bilayers via liposome fusion on polymer
      cushions.

PMID- 30226256
TI  - Catalytic enantioselective one-pot approach to cis- and trans-2,3-diaryl
      substituted 1,5-benzothiazepines.
AB  - The first enantioselective catalytic approach to cis- and trans-2,3-diaryl
      substituted 1,5-benzothiazepines has been conveniently developed in a one-pot
      fashion, starting from alpha,beta-unsaturated acyl pyrazoles and 2
      aminothiophenol. The organocatalytic two-step sulfa-Michael/lactamization
      sequence is promoted by a readily available bifunctional thiourea and p
      toluenesulfonic acid, respectively. The protocol enables access to both N
      unprotected cis- and trans-diastereoisomers in moderate to satisfactory overall
      yields (up to 84%) and good to excellent ee values (up to 99%). Mechanistic
      investigations helped to shed light on the regio- and stereoselective outcome of
      the process.

PMID- 30226257
TI  - Molecular reorganization in bulk bottlebrush polymers: direct observation via
      nanoscale imaging.
AB  - Bottlebrush polymers are important for a variety of applications ranging from
      drug delivery to electronics. The functional flexibility of the branched
      sidechains has unique assembly properties when compared to linear block polymer
      systems. However, reports of direct observation of molecular reorganization have
      been sparse. This information is necessary to enhance the understanding of the
      structure-property relationships in these systems and yield a rational design
      approach for novel polymeric materials. In this work, we report direct
      visualization of bottlebrush molecular organization and the formation of nematic
      type ordering in an amorphous polymer bottlebrush system, captured with plasma
      etching and helium ion microscopy. By observing the unperturbed structure of this
      material at high resolution and quantifying image features, we were able to
      qualitatively link experimental results with structures predicted by coarse
      grained molecular dynamics simulations. The direct visualization and computation
      workflow developed in this work can be applied to a broad variety of polymers
      with different architectures, linking imaging results with other, independent
      channels of information for better understanding and control of these classes of
      materials.

PMID- 30226258
TI  - Robust Buchwald-Hartwig amination enabled by ball-milling.
AB  - An operationally simple mechanochemical method for the Pd catalysed Buchwald
      Hartwig amination of arylhalides with secondary amines has been developed using a
      Pd PEPPSI catalyst system. The system is demonstrated on 30 substrates and
      applied in the context of a target synthesis. Furthermore, the performance of the
      reaction under aerobic conditions has been probed under traditional solution and
      mechanochemical conditions, the observations are discussed herein.

PMID- 30226259
TI  - Tailoring the nonlinear optical performance of two-dimensional MoS2 nanofilms via
      defect engineering.
AB  - Defect engineering plays a key role in determining the catalytic and optical
      properties of two-dimensional (2D) materials such as molybdenum disulfide (MoS2)
      in their practical applications in optical and photonic devices. Here, we report
      a direct strategy for the fabrication of wafer-scale 2D MoS2 nanofilms with
      tunable sulfur (S) vacancies and crystallinity by a modified solvothermal method
      via a polyelectrolyte-assisted annealing process. Our results demonstrate that
      the S vacancies in MoS2 nanofilms can induce saturable absorption (SA) in MoS2 by
      introducing new energy bands within the band gap of MoS2, and the crystallinity
      has a significant effect on the two-photon absorption (TPA) coefficient of MoS2
      nanofilms. The SA responses in MoS2 will gradually dominate the nonlinear optical
      (NLO) behavior of MoS2 with a lower saturable intensity along with increasing the
      S vacancies. The TPA coefficient of the MoS2 nanofilms with increased
      crystallinity is improved to (4.3 +/- 0.5) * 102 cm GW-1 on increasing the
      crystallinity of MoS2 films, over four times larger than that of their
      counterpart with relatively low crystallinity. Additionally, the damage threshold
      of MoS2 nanofilms after polyelectrolyte-assisted annealing treatment is greatly
      improved to ~74.1 GW cm-2 compared to ~32.6 GW cm-2 of their counterpart with few
      S vacancies and relatively low crystallinity, due to the increased crystallinity
      and partial oxidation of MoS2. This work sheds light on how the defects tailor
      the nonlinear optical properties of 2D MoS2 nanofilms and affords an effective
      strategy for defect engineering via a polyelectrolyte-assisted annealing process,
      which can be applied to other 2D transition metal dichalcogenides.

PMID- 30226260
TI  - Exciton and phonon dynamics in highly aligned 7-atom wide armchair graphene
      nanoribbons as seen by time-resolved spontaneous Raman scattering.
AB  - The opening of a band gap in graphene nanoribbons induces novel optical and
      electronic properties, strongly enhancing their application potential in
      nanoscale devices. Knowledge of the optical excitations and associated relaxation
      dynamics are essential for developing and optimizing device designs and
      functionality. Here we report on the optical excitations and associated
      relaxation dynamics in surface aligned 7-atom wide armchair graphene nanoribbons
      as seen by time-resolved spontaneous Stokes and anti-Stokes Raman scattering
      spectroscopy. On the anti-Stokes side we observe an optically induced increase of
      the scattering intensity of the Raman active optical phonons which we assign to
      changes in the optical phonon populations. The optical phonon population decays
      with a lifetime of ~2 ps, indicating an efficient optical-acoustic phonon cooling
      mechanism. On the Stokes side we observe a substantial decrease of the phonon
      peak intensities which we relate to the dynamics of the optically induced exciton
      population. The exciton population shows a multi-exponential relaxation on the
      hundreds of ps time scale and is independent of the excitation intensity,
      indicating that exciton-exciton annihilation processes are not important and the
      exsistence of dark and trapped exciton states. Our results shed light on the
      optically induced phonon and exciton dynamics in surface aligned armchair
      graphene nanoribbons and demonstrate that time-resolved spontaneous Raman
      scattering spectroscopy is a powerful method for exploring quasi-particle
      dynamics in low dimensional materials.

PMID- 30226263
TI  - X-ray structure and magnetic and fluorescence characteristics of new Cu(ii)
      complexes with Schiff bases derived from 2-(2-aminoethyl)pyridine and 2-hydroxy-1
      naphthaldehyde; morphology and fluorescence of their thin films.
AB  - Cu(ii) complexes with tridentate Schiff bases derived from 2-(2
      aminoethyl)pyridine and 2-hydroxy-1-naphthaldehyde and COO-, Cl- and NO3- as
      ligands were obtained and characterized by crystal and molecular, spectroscopic
      (UV-Vis, fluorescence, IR, and EPR), magnetic and thermal methods. The X-ray
      crystal structure analysis revealed a distorted square planar geometry for
      [Cu(ii)(PEMN)CH3COO]CHCl3, 1, and [Cu(ii)(PEMN)Cl], 2, and a distorted square
      pyramidal geometry for [Cu(ii)(PEMN)NO3], 3, corresponding to the values of EPR g
      matrix diagonal components. The copper(ii) complexes exhibited fluorescence in
      solution in the range of 370-410 nm. Thin layers of the studied copper(ii)
      complexes were deposited on Si(111) by a spin coating method and studied by
      scanning electron microscopy (SEM/EDS), atomic force microscopy (AFM) and
      fluorescence spectroscopy. For copper(ii) layers (2/Si), the most intense
      fluorescence band from an intraligand and a d-d transition between 490 and 550 nm
      was observed.

PMID- 30226264
TI  - Changes in spatio-temporal localization of tripeptidyl peptidase II (TPPII) in
      murine colon adenocarcinoma cells during aggresome formation: a microscopy study
      based on a novel fluorescent proteasome inhibitor.
AB  - Extralysosomal proteolysis is a multistep process involving the Ubiquitin-
      Proteasome System (UPS) and supplementary peptidases. Tripeptidyl peptidase II
      (TPPII) is the most extensively characterized enzyme, supplementing and sometimes
      substituting for proteasomal functions. In response to proteasome inhibition,
      polyubiquitinated proteins acting as proteasome substrates aggregate with
      proteasomes and form aggresomes. Several proteasome inhibitors are used as anti
      cancer drugs. Thus, in our study, we used a novel fluorescent-tagged proteasome
      inhibitor BSc2118 to induce aggresome formation in C26 murine colon
      adenocarcinoma cells. It allowed us to obtain effective, inhibitor-based,
      proteasome staining in vivo. This method has been validated by standard post
      fixed indirect immunostaining and also allowed co-immunodetection of TPPII and
      polyubiquitinated proteins under laser scanning confocal microscopy. We found
      that in the absence of the inhibitor, TPPII is diffusely dispersed within the
      cytoplasm of C26 cells. The proteasome and ubiquitin-rich perinuclear region
      failed to display enhanced TPPII staining. However, when proteasome function was
      impaired by the inhibitor, TPPII associated more closely with both the proteasome
      and polyubiquitinated proteins via TPPII recruitment to the perinuclear region
      and subsequently into emerging aggresomal structures. Furthermore, we have
      demonstrated the dynamic recruitment of TPPII into the developing aggresome:
      TPPII in the early aggresome was dispersed within the central part but
      subsequently aggregated on the surface of this structure. In the mature aggresome
      of C26 cells TPPII formed a spherical mantle, which surrounded the round core
      containing proteasomes and polyubiquitinated proteins. Our morphological data
      indicate that TPPII displays spatial localization with proteasomes especially
      upon proteasome inhibition in aggresomes of C26 cells.

PMID- 30226265
TI  - Potential of recovered proteins from invasive green crabs (Carcinus maenas) as a
      functional food ingredient.
AB  - BACKGROUND: Invasive green crabs contain high-quality proteins that have
      potential as functional ingredients in formulated foods. This study evaluated the
      functional properties and compositional characteristics of green crab proteins
      recovered by isoelectric solubilization/precipitation (ISP). RESULTS:
      Mechanically separated green crab mince (control) was solubilized at pH 2 (PP2)
      and pH 10 (PP10), then proteins were precipitated at pH 5.5 and subsequently
      dried. Yield of recovered protein powder was approximately 1.5 times higher for
      PP2 than for PP10. Compared with the control (230 g kg-1 ), ash content was
      reduced in PP2 (54 g kg-1 ) and PP10 (23 g kg-1 ) samples. PP2 contained
      predominantly large-molecular-weight proteins, while small-molecular-weight
      proteins were distributed in PP10. With regard to functional properties, at pH 7
      and 8, solubility of PP10 was significantly higher than that of PP2. At pH 7.5,
      PP10 exhibited significantly higher emulsifying activity (1482 m2  g-1 ) than PP2
      (858 m2  g-1 ) and the control (958 m2  g-1 ). PP2 showed statistically higher
      gelation activity and had higher L* value than PP10 and the control. CONCLUSION:
      The results indicate that recovered green crab proteins have functional
      properties potentially useful for formulated foods, and that these functional
      properties can be modified by the solubilization pH during the recovery process.
      (c) 2018 Society of Chemical Industry.

PMID- 30226266
TI  - Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes
      lipophagy and chemosensitivity in gynecologic cancers.
AB  - Metabolic alterations are increasingly recognized as important novel anti-cancer
      targets. Among several regulators of metabolic alterations, fructose 2,6
      bisphosphate (F2,6BP) is a critical glycolytic regulator. Inhibition of the
      active form of PFKFB3ser461 using a novel inhibitor, PFK158 resulted in reduced
      glucose uptake, ATP production, lactate release as well as induction of apoptosis
      in gynecologic cancer cells. Moreover, we found that PFK158 synergizes with
      carboplatin (CBPt) and paclitaxel (PTX) in the chemoresistant cell lines, C13 and
      HeyA8MDR but not in their chemosensitive counterparts, OV2008 and HeyA8,
      respectively. We determined that PFK158-induced autophagic flux leads to
      lipophagy resulting in the downregulation of cPLA2, a lipid droplet (LD)
      associated protein. Immunofluorescence and co-immunoprecipitation revealed
      colocalization of p62/SQSTM1 with cPLA2 in HeyA8MDR cells uncovering a novel
      pathway for the breakdown of LDs promoted by PFK158. Interestingly, treating the
      cells with the autophagic inhibitor bafilomycin A reversed the PFK158-mediated
      synergy and lipophagy in chemoresistant cells. Finally, in a highly metastatic
      PTX-resistant in vivo ovarian mouse model, a combination of PFK158 with CBPt
      significantly reduced tumor weight and ascites and reduced LDs in tumor tissue as
      seen by immunofluorescence and transmission electron microscopy compared to
      untreated mice. Since the majority of cancer patients will eventually recur and
      develop chemoresistance, our results suggest that PFK158 in combination with
      standard chemotherapy may have a direct clinical role in the treatment of
      recurrent cancer.

PMID- 30226267
TI  - Biological films adhering to the oral soft tissues: Structure, composition, and
      potential impact on taste perception.
AB  - : The role of free-flowing saliva in taste perception is increasingly recognized,
      but saliva is also present in the mouth as films intimately associated to soft or
      hard tissues. On mucosal surfaces, particularly on the tongue, the structure and
      composition of such films (including its microbial constitutive part) may play a
      particular role in the sense of taste due to their proximity with the taste
      anatomical structures. This review compiles the current knowledge on the
      structure of biological films adhering to oral mucosae and on their biochemical
      and microbiological composition, before presenting possible implications for
      taste perception. PRACTICAL APPLICATIONS: The understanding of the role of oral
      biological films on taste perception may provide new avenues of research and
      development for the industry or academia interested broadly in chemosensation.

PMID- 30226268
TI  - Preparation, characterization and physicochemical properties of novel low
      phosphorus egg yolk protein.
AB  - BACKGROUND: In order to supply adequate dietary protein for chronic kidney
      disease (CKD) patients while simultaneously controlling phosphorus intake, a
      novel method was developed for the preparation of low-phosphorus egg yolk protein
      (LPYP) using alkaline protease auxiliary dephosphorization. In addition, the
      physicochemical properties of LPYP were studied. RESULTS: In comparison with raw
      egg yolk protein (RYP) and defatted egg yolk protein (DFYP), LPYP was found to
      exhibit differences in amino acid (AA) composition, protein secondary structure,
      surface hydrophobicity, solubility and emulsion stability. It was observed that
      dephosphorization improved the AA composition, soluble protein content and
      dissolution stability of egg yolk protein. In addition, phosphate groups were
      found to impose a critical influence on the emulsion stability and particle size
      distribution. The final phosphorus to protein mass ratio (P/Pro) of LPYP was
      5.64, which met the requirements of a protein diet for CKD patients. The FAO/WHO
      mode closeness and stability coefficient were 0.958 and 98.62% respectively.
      CONCLUSION: LPYP can be effectively obtained by alkaline protease hydrolysis and
      subsequent alkali dephosphorization. The prepared LPYP can be considered to be a
      type of safe and suitable protein resource for CKD patients. (c) 2018 Society of
      Chemical Industry.

PMID- 30226269
TI  - Systematic identification of lincRNA-based prognostic biomarkers by integrating
      lincRNA expression and copy number variation in lung adenocarcinoma.
AB  - Copy number alterations (CNAs) of lincRNAs act as one of important mechanisms in
      disrupting lincRNA expression which may play critical roles during tumorigenesis
      in lung adenocarcinoma (LUAD). The copy number alterations of lincRNAs can mark
      the spectrum of cancer progression and may serve as biomarkers for prognosis in
      LUAD, however it is rarely studied. We analyzed RNASeq data for 488 LUAD patients
      from TCGA portal and 58 healthy subjects to identify prognostic lincRNAs
      predictive of patient survival. Computational analysis entailing integration of
      expression and copy number alteration data revealed five prognostic lincRNAs:
      RBPMS-AS1, TDRKH-AS1, LINC00578, RP11-470M17.2 and LINC00941. The copy number
      alterations in the LINC00578 and RP11-470M17.2 genes were positively associated
      with the longer overall survival of LUAD patients. The CNA in LINC00941 was
      negatively associated with the longer overall survival. Copy number amplification
      significantly correlated with increased expression of TDRKH-AS1, which regulates
      telomere organization and EZH2-mediated epigenetic silencing of CDKN1A, CDKN1B
      and IL24. Decreased survival of LUAD patients was associated with high LINC00941
      expression. The LINC00941 regulates the PI3K-AKT signaling pathway, focal
      adhesion by influencing potential targets, such as KRAS proto-oncogene GTPase and
      VEGFC. These lincRNA-based prognostic biomarkers may destroy important cancer
      related biological processes contributing to LUAD prognosis. In summary, we
      demonstrate the prognostic potential of four differentially expressed lincRNAs
      with copy number alterations (RBPMS-AS1, TDRKH-AS1, LINC00578 and RP11-470M17.2)
      that are positively associated with longer overall survival of LUAD patients. One
      differentially expressed lincRNA LINC00941 with copy number alterations was
      negatively associated with longer overall survival of LUAD patients. This article
      is protected by copyright. All rights reserved.

PMID- 30226270
TI  - Hidden state models improve state-dependent diversification approaches, including
      biogeographical models.
AB  - The state-dependent speciation and extinction (SSE) models have recently been
      criticized due to their high rates of "false positive" results. Many researchers
      have advocated avoiding SSE models in favor of other "nonparametric" or
      "semiparametric" approaches. The hidden Markov modeling (HMM) approach provides a
      partial solution to the issues of model adequacy detected with SSE models. The
      inclusion of "hidden states" can account for rate heterogeneity observed in
      empirical phylogenies and allows for reliable detection of state-dependent
      diversification or diversification shifts independent of the trait of interest.
      However, the adoption of HMM has been hampered by the interpretational challenges
      of what exactly a "hidden state" represents, which we clarify herein. We show
      that HMMs in combination with a model-averaging approach naturally account for
      hidden traits when examining the meaningful impact of a suspected "driver" of
      diversification. We also extend the HMM to the geographic state-dependent
      speciation and extinction (GeoSSE) model. We test the efficacy of our "GeoHiSSE"
      extension with both simulations and an empirical dataset. On the whole, we show
      that hidden states are a general framework that can distinguish heterogeneous
      effects of diversification attributed to a focal character.

PMID- 30226271
TI  - The role of multimodal treatment in Crohn's disease patients with perianal
      fistula: a multicentre retrospective cohort study.
AB  - BACKGROUND: Treatment paradigms for Crohn's disease with perianal fistulae (CD
      pAF) are evolving. AIMS: To study the impact of multimodality treatment in CD-pAF
      on recurrence rates and the need for re-interventions and to identify predictive
      factors for these outcomes. METHODS: This was a multinational multicentre
      retrospective cohort study. Multimodality approach was defined as using a
      combination of medical treatments (anti-TNFs +/- immunomodulators +/-
      antibiotics) along with surgical approach (examination under anaesthesia (EUA) +/
      seton drainage) at diagnosis of CD-pAF. Univariable and multivariable analyses
      were performed for variables indicative of the need for reintervention. RESULTS:
      A total of 253 patients were included. 65% of patients received multimodality
      approach. Multimodality treatment resulted in complete fistula healing in 52% of
      patients. Re-intervention was needed in 27% of patients with simple and in 40.3%
      of those with complex fistula. On multivariable analysis multimodality treatment
      (OR: 0.35, 95% CI: 0.17-0.57, P = 0.001), seton removal (OR: 0.090, 95% CI: 0.027
      0.30, P = 0.0001, therapy with infliximab (OR: 0.19, 95% CI: 0.06-0.64, P =
      0.007), and therapy with adalimumab (OR: 0.12, "95% CI: 0.026-0.56, P = 0.007)
      were predictive of avoiding repeat surgery. Proctitis (OR: 3.76, 95% CI: 1.09
      12.96, P = 0.03) was predictive of the need for radical surgery (proctectomy,
      diverting stoma) while multimodality treatment reduced the need for radical
      surgery (OR: 0.21, 95% CI: 0.05-0.81, P = 0.02). CONCLUSIONS: Multimodality
      treatment, anti-TNFs use, and removal of setons after multimodality treatment can
      result in improved outcomes in CD patients with perianal fistulae and reduce the
      need for repeat surgery and radical surgery.

PMID- 30226272
TI  - Curcumin analogs: their roles in pancreatic cancer growth and metastasis.
AB  - Curcumin is a polyphenolic constituent of turmeric that is known to have various
      molecular effects in preclinical models, leading to prevention and anti-cancer
      properties. In clinical trials, curcumin has failed to demonstrate activity
      against pancreatic cancer possibly due to its low bioavailability and potency.
      Using the curcumin molecular model, our group and others have synthesized several
      analogs with better bioavailability and higher potency in pancreatic cancer in
      vitro and xenograft models. This mini review summarizes some of the known
      molecular effects of curcumin analogs and their potential role as novel
      therapeutics for pancreatic cancer. This article is protected by copyright. All
      rights reserved.

PMID- 30226273
TI  - The chemical profiling of fatty acids during the brewing process.
AB  - BACKGROUND: Although fatty acids have a beneficial effect on yeast growth during
      fermentation, their effect on foam and sensory stability of beer is negative. In
      general, long-chain fatty acids originate from raw materials, whereas short-chain
      acids are produced by yeast during fermentation. If the concentration of short
      chain fatty acids, especially isovaleric and butyric acid, overreaches a sensory
      threshold, then an unpleasant aroma, such as cheesy or sweaty feet, can be formed
      in beer. RESULTS: The distribution of fatty acids, from the preparation of sweet
      wort to the final beer, was studied using chemometric evaluation. Differences
      were observed between the decoction and infusion system using four barley
      varieties. Attention was paid to the behavior of short-chain fatty acids, namely
      isovaleric acid. The concentration of isovaleric acid in commercial beers brewed
      in infusion and decoction systems was approximately 1.4 and 1.0 mg L-1 ,
      respectively. The same trend was observed in experimental samples (1.3 and 0.5 mg
      L-1 , respectively). This phenomenon was confirmed experimentally; based on the
      results, this possibly explains why, during the fermentation, isovaleric acid is
      coupled with the redox state of yeast cell, which is given by the wort
      composition (i.e. by the mashing process). CONCLUSION: The formation of
      isovaleric acid is not only caused by microbiology infection or by oxidized hops,
      but also is influenced by the mashing process. (c) 2018 Society of Chemical
      Industry.

PMID- 30226275
TI  - The quality of platelet concentrates related to corrected count increment:
      linking in vitro to in vivo.

PMID- 30226274
TI  - Inequity of care provision and outcome disparity in autoimmune hepatitis in the
      United Kingdom.
AB  - BACKGROUND: Treatment paradigms in autoimmune hepatitis (AIH) have remained
      largely unchanged for decades. Studies report <=20% of patients have sub-optimal
      treatment response with most requiring long-term therapy. AIM: The United Kingdom
      Autoimmune Hepatitis (UK-AIH) study was established to evaluate current treatment
      practice and outcomes, determine the unmet needs of patients, and develop and
      implement improved treatment approaches. METHODS: The United Kingdom Autoimmune
      Hepatitis study is a cross-sectional cohort study examining secondary care
      management of prevalent adult patients with a clinical diagnosis of autoimmune
      hepatitis. Enrolment began in March 2014. Prevalent cases were defined as having
      been diagnosed and treated for >1 year. Demographic data, biochemistry, treatment
      history and response, and care location were collected. RESULTS: In total, 1249
      patients were recruited; 635 were cared for in transplant units and 614 in non
      transplant centres (81% female with median age at diagnosis 50 years). Overall,
      29 treatment regimens were reported and biochemical remission rate was 59%.
      Remission rates were significantly higher in transplant compared to non
      transplant centres (62 vs 55%, P = 0.028). 55% have ongoing corticosteroid
      exposure; 9% are receiving prednisolone monotherapy. Those aged <=20 years at
      diagnosis were more likely to develop cirrhosis and place of care was associated
      with an aggressive disease phenotype. CONCLUSIONS: There are significant
      discrepancies in the care received by patients with autoimmune hepatitis in the
      UK. A high proportion remains on corticosteroids and there is significant
      treatment variability. Patients receiving care in transplant centres were more
      likely to achieve and maintain remission. Overall poor remission rates suggest
      that there are significant unmet therapeutic needs for patients with autoimmune
      hepatitis.

PMID- 30226276
TI  - Ras association domain family 1 isoform A suppresses colonic tumor cell growth
      through p21WAF1 activation in a p53-dependent manner.
AB  - BACKGROUND AND AIM: Despite the frequent loss of Ras association domain family 1
      isoform A (RASSF1A) expression in various cancers, the precise mechanism
      underlying its tumor-suppressive effect is not fully understood. To elucidate the
      growth-inhibitory role for RASSF1A in colorectal tumorigenesis, this study
      investigated the RASSF1A regulation of the p53-p21WAF1 pathway. METHODS: Ras
      association domain family 1 isoform A effect on cellular growth was tested in
      three human colon cancer cell lines by flow cytometry, cell counting, and [3 H]
      thymidine incorporation assay. HCT116 p53+/+ and p53-/- isogenic sublines were
      utilized to determine the p53 dependence of RASSF1A effect on p21WAF1 .
      Cycloheximide chase experiment and immunoprecipitation assay were carried out to
      define RASSF1A effect on p53 stability and mouse double minute 2 (MDM2) homolog
      ubiquitination. RESULTS: Ras association domain family 1 isoform A expression
      inhibits colonic cell proliferation by preventing the G1 to S phase transition of
      the cell cycle. The RASSF1A-induced G1 cell cycle arrest is accompanied by the
      increase in the level of p21WAF1 mRNA expression. The p21WAF -inducing activity
      of RASSF1A was substantially higher in HCT116 p53+/+ cell compared with isogenic
      p53-/- cells. The cycloheximide chase assay revealed that RASSF1A expression
      leads to p53 stabilization and MDM2 homolog degradation. Using p53-/- and p21WAF1
      /- subline cells, this study finally validated a crucial role of the p53-p21WAF1
      axis in RASSF1A-mediated growth inhibition. CONCLUSIONS: RASSF1A suppresses
      colonic tumor growth through the activation of the p53-p21WAF1 pathway. This
      finding supports that RASSF1A could be a valuable marker for the assessment of
      colorectal cancer development and progression.

PMID- 30226277
TI  - NaCl stress on physio-biochemical metabolism and antioxidant capacity in
      germinated hulless barley (Hordeum vulgare L.).
AB  - BACKGROUND: Hulless barley generally grows in barren fields, where soil
      salinization is serious. However, only a few studies have been carried out
      investigating germinated hulless barley under salt stress. In the present study,
      the effect of NaCl stress on the physio-biochemical metabolism and antioxidant
      capacity of germinated hulless barley was investigated. RESULTS: NaCl stress
      inhibited seedling growth and caused oxidative damage, although it enhanced the
      accumulation of phenolic compounds and antioxidant capacity. The highest contents
      of total phenolic and main phenolic acids (vanillic acid, p-coumaric acid,
      ferulic acid and sinapic acid) were found with 60 mmol L-1 NaCl treatment,
      whereas 120 mmol L-1 NaCl inhibited the synthesis of phenolic components. Gene
      expression of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase
      (C4H), 4-coumarate coenzyme A ligase (4CL), p-coumaric acid 3-hdroxylase (C3H)
      and caffeic acid/5-hydroxyferulic acid O-methyltransferase (COMT), which
      participated in the synthesis of phenolic compounds, was up-regulated by NaCl
      stress, as were the enzyme activities of PAL, C4H and 4CL. NaCl treatment also
      enhanced the antioxidant enzyme activities of germinated hulless barley.
      CONCLUSION: NaCl stress inhibited seedlings growth and caused oxidative damage.
      Simultaneously, the antioxidant system of germinated hulless barley was enhanced.
      The results of the present study provide a theoretical basis with respect to the
      growth of hulless barley under salt stress. (c) 2018 Society of Chemical
      Industry.

PMID- 30226278
TI  - Ethical issues in research on substance-dependent parents: The risk of implicit
      normative judgements by researchers.
AB  - When doing research among vulnerable populations, researchers are obliged to
      protect their subjects from harm. We will argue that traditional ethical
      guidelines are not sufficient to do this, since they mainly focus on direct harms
      that can occur: for example, issues around informed consent, fair recruitment and
      risk/harm analysis. However, research also entails indirect harms that remain
      largely unnoticed by research ethical committees and the research community.
      Indirect harms do not occur during data collection, but in the analysis of the
      data, and how the data is presented to the scientific and wider societal
      community. Highly stigmatized research subjects, like substance-dependent
      parents, are especially at risk of encountering indirect harm, because the
      prejudice against them is so persistent. In this paper we discuss two forms of
      indirect harm. First, researchers have to be aware how their results will be
      preceived by society. Even when subjects are presented in an objective way,
      further, out of porportion stigmatization can occur. Researchers sometimes try to
      counteract this by whitewashing their results, at the risk of downplaying their
      respondents' problems. The second risk researchers face is that their own
      normative judgements influence how they question such parents, report results and
      interpret statements. Researchers' own normative judgements may influence the way
      they present their subjects. This article reviews a broad range of research that
      exhibits such indirect harms, discussing how and why indirect harms occur and
      formulating corresponding recommendations on how to prevent them.

PMID- 30226279
TI  - Dual-Carbon-Confined Fe7 S8 Anodes with Enhanced Electrochemical Catalytic
      Conversion Process for Ultralong Lithium Storage.
AB  - Although the electrochemical catalytic conversion process is effective in
      increasing the reversible capacity of lithium-ion batteries, the low contact
      efficiency between metal catalyst and substrate and pulverization of the solid
      electrolyte interface (SEI) film without protection are not beneficial for the
      electrochemical reactions. Herein, Fe7 S8 nanoparticles are confined by both
      reduced graphene oxide (RGO) and in-situ-formed amorphous carbon (C) to form dual
      carbon-confined Fe7 S8 as a lithium-ion anode. The dual-carbon-confined structure
      provides a confined space to prevent pulverization of the SEI film and increases
      the local concentration of intermediate phases, which could be
      electrocatalytically decomposed by Fe nanoparticles formed in situ to increase
      the reversibility of the electrochemical reactions and gain high reversible
      capacity. In addition, the dual-carbon-confined structure ensures fast transfer
      of electrons and boosts transport of lithium ions due to the highly conductive
      dual-carbon shell. Thus, the Fe7 S8 /C/RGO anode delivers an excellent rate
      performance and long cycling stability. At current densities of 2000 and 5000 mA
      g-1 , the reversible capacities are 520 mA h g-1 over 1500 cycles and 294 mA h g
      1 over 2000 cycles, respectively.

PMID- 30226280
TI  - Suffering at the end of life.
AB  - In the end-of-life context, alleviation of the suffering of a distressed patient
      is usually seen as a, if not the, central goal for the medical personnel treating
      her. Yet it has also been argued that suffering should be seen as a part of good
      dying. More precisely, it has been maintained that alleviating a dying patient's
      suffering can make her unable to take care of practical end-of-life matters,
      deprive her of an opportunity to ask questions about and find meaning in and for
      her existence, and detach her from reality. In this article, I argue that the
      aims referred to either do not support suffering or are better served by
      alleviating it. When the aims would be equally well served by enduring suffering
      and relieving it, the latter appears to be the preferable option, given that the
      distress a patient experiences has no positive intrinsic value. Indeed, as the
      suffering can be very distressing, it may not be worth bearing even if that was
      the best way to achieve the aims: the distress can sometimes be bad enough to
      outbalance the worth of achieving the goals. Having considered an objection to
      the effect that a patient can have a self-regarding moral duty to endure the
      distress she faces at the end of life, I conclude that the burden of proof is on
      the side of those who maintain that the suffering experienced at the end of life
      ought to be endured as a part of dying well.

PMID- 30226281
TI  - The effect of an ex vivo boosted immune cell therapy on canine atopic dermatitis:
      an open, uncontrolled pilot study.
AB  - BACKGROUND: Canine atopic dermatitis (cAD) is associated with an imbalance
      between multiple T lymphocytes and cytokines. Ex vivo boosted immune cell (EBIC)
      therapy is the sequential administration of ex vivo cultured and activated
      lymphocytes to patients to improve immune function. OBJECTIVE: This pilot study
      aimed to assess the safety of EBIC therapy and demonstrate its efficacy as a
      novel treatment for cAD. ANIMALS: Ten dogs with AD. METHODS AND MATERIALS: The
      phenotypes of the immune cells before and after ex vivo culture were analysed by
      flow cytometry. EBICs (1.0-5.0 * 108 cells/animal) were administered to dogs
      every two weeks, with a total of six injections. The cAD extent and severity
      index (CADESI)-03 and pruritus scores were calculated to evaluate the efficacy of
      EBIC therapy for cAD. For safety assessment, regular blood examination was
      conducted, and any adverse events recorded. The serum levels of interleukin (IL)
      4, IL-10, IL-31 and interferon-gamma (IFN-gamma) were evaluated. RESULTS: The
      cells expanded by an average of 57.52-fold and the proportions of CD8+ cells and
      IFN-gamma-producing cells significantly increased after ex vivo culture.
      Sequential EBIC therapy improved CADESI-03, and pruritus scores significantly.
      After stopping treatment the improvement rates increased for the CADESI score and
      were maintained for the pruritus score. There were no significant changes in
      cytokine levels. No significant adverse events were observed. CONCLUSIONS AND
      CLINICAL SIGNIFICANCE: EBIC therapy is a safe and efficient treatment for cAD.
      This therapy could correct the immunological imbalance in dogs with AD by
      infusing activated T lymphocytes.

PMID- 30226282
TI  - A simple 1 H NMR based assay of total capsaicinoid levels in Capsicum using
      signal suppression in non-deuterated solvent.
AB  - BACKGROUND: The heat of Capsicum fruits is routinely assayed using high
      performance liquid chromatography (HPLC) to determine capsaicin (CA) and
      dihydrocapsaicin (DHC) levels. The assay can be time consuming, with each HPLC
      run typically lasting 10 min. Nuclear magnetic resonance (NMR) is eminently
      suitable for quantification of fruit extracts, although it has been largely
      ignored for quantitative chilli analysis. The present study describes a novel
      approach using solvent suppression in protic solvent (i.e. non-deuterated) to
      quantify total capsaicinoid levels in chilli extracts. RESULTS: Using solvent
      suppression techniques and maleic acid as an internal standard, capsaicinoid
      content in a series of accurately weighed standard samples was determined over a
      range between 40 and 720 ppm (0.13-2.35 mmolar) with high accuracy and precision.
      The measurement was linear over the entire range. This method was subsequently
      used with ten authentic Capsicum samples (seven chinense, two annuum and one
      baccatum) and showed an excellent correlation with the HPLC data. CONCLUSION: The
      results of the present study confirm that NMR in non-deuterated solvent can
      provide a rapid and robust assessment of the pungency of capsicum fruits. (c)
      2018 Society of Chemical Industry.

PMID- 30226283
TI  - Regulatory T-cells: receptors, repertoires and roles in disease.
AB  - In the 20-or-so years that immunologists have spent describing the mechanisms and
      functions of regulatory T-cells, a very great deal has been learnt: a T-cell
      subset once described for the generic ability to harness autoimmunity in vivo or
      diminish T-cell proliferation in vitro is now appreciated to act on a plethora of
      cellular pathways using a diverse array of mechanisms. Recent studies have shed
      new light on basic and applied aspects of Treg function, including T-cell
      receptor usage, specialist functions of tissue-resident Tregs, and the
      therapeutic consequences of tuning Treg function up or down for applications in
      autoimmunity or cancer, respectively.

PMID- 30226284
TI  - The value of work: Addressing the future of work through the lens of solidarity.
AB  - Designing the future of work is crucial to the health and well-being of people
      and societies. Experts predict that developments such as the advancement of
      digital technologies, automation, and the movement of manufacturing jobs to low
      wage countries will lead to major transformations in the labour market, and some
      foresee significant job losses. Due to the close relationship between employment
      and health, major job losses would have significant negative impacts on the
      health and well-being of individuals and societies. Job losses would also pose a
      major challenge to solidaristic support within societies because they would
      negatively affect the recognition of similarities among people, which is vital
      for solidaristic practice and institutions. To prevent these negative effects, a
      fundamental redesign of the relationship between work and income is necessary.
      And for this project to succeed, we need to reconsider of the value of work.
      Building on definitions of flourishing people and societies, we argue that the
      value of work should not be determined by the labour market, but according to its
      importance for society. Using a solidarity-based framework we argue that such a
      re-valuation of work will help to ensure social cohesion and increase reciprocity
      in our societies. It will serve as a foundation upon which we can reconfigure the
      relationship between work and income without risking the loss of social cohesion
      and solidarity.

PMID- 30226285
TI  - High-density characterization of a localized reentry circuit occurred after AF
      ablation.
AB  - We present the case of a localized reentry circuit that developed 24 h after
      radiofrequency ablation of atrial fibrillation (AF). The circuit was of interest
      because it overlapped with sites of previous defragmentation during AF. The
      circuit presented a small funnel that measured only 1.4 mm at its narrowest
      segment. Fractionated signals, which codify for slow conduction zones,
      corresponded to the isthmus site. Ablation at this site interrupted the atrial
      tachycardia.

PMID- 30226286
TI  - Treatment data and technical process challenges for practical big data efforts in
      radiation oncology.
AB  - The term Big Data has come to encompass a number of concepts and uses within
      medicine. This paper lays out the relevance and application of large collections
      of data in the radiation oncology community. We describe the potential importance
      and uses in clinical practice. The important concepts are then described and how
      they have been or could be implemented are discussed. Impediments to progress in
      the collection and use of sufficient quantities of data are also described.
      Finally, recommendations for how the community can move forward to achieve the
      potential of big data in radiation oncology are provided.

PMID- 30226287
TI  - Low-dose daily aspirin reduces topical minoxidil efficacy in androgenetic
      alopecia patients.
AB  - Topical minoxidil is the only US FDA approved OTC drug for the treatment of
      androgenetic alopecia (AGA). Minoxidil is a pro-drug converted into its active
      form, minoxidil sulfate, by the sulfotransferase enzymes in the outer root sheath
      of hair follicles. Previously, we demonstrated that sulfotransferase activity in
      hair follicles predicts response to topical minoxidil in the treatment of AGA. In
      the human liver, sulfotransferase activity is significantly inhibited by
      salicylic acid. Low-dose OTC aspirin (75-81 mg), a derivative of salicylic acid,
      is used by millions of people daily for the prevention of coronary heart disease
      and cancer. It is not known whether oral aspirin inhibits sulfotransferase
      activity in hair follicles, potentially affecting minoxidil response in AGA
      patients. In the present study, we determined the follicular sulfotransferase
      enzymatic activity following 14 days of oral aspirin administration. In our
      cohort of 24 subjects, 50% were initially predicted to be responders to
      minoxidil. However, following 14 days of aspirin administration, only 27% of the
      subjects were predicted to respond to topical minoxidil. To the best of our
      knowledge, this is the first study to report the effect of low-dose daily aspirin
      use on the efficacy of topical minoxidil.

PMID- 30226288
TI  - An Update on Patents Covering Agents That Interfere with the Cancer Glycolytic
      Cascade.
AB  - Many tumors exhibit altered metabolic characteristics relative to normal and
      healthy tissues. Their metabolic profile highlights a strong prevalence of
      glycolysis over oxidative phosphorylation, regardless of their exposure to
      different oxygen levels (the Warburg effect). This condition originates from a
      set of gene regulations, consisting of the overexpression of some enzymes or
      transporters involved in the glycolytic pathway. Therefore, these effectors may
      constitute appealing targets for the implementation of selective therapeutic
      interventions against cancer. Recently, significant progress has been made in the
      discovery of molecules that act at various levels of the glycolytic pathway of
      tumor cells. So far, some of the most widely explored targets of the glycolytic
      cascade are represented by glucose transporters, hexokinase, 6
      phosphofructokinase, enolase, pyruvate kinase, lactate dehydrogenase, and
      monocarboxylate transporters. The purpose of this minireview is to provide an
      update on some of the most recently patented bioactive molecules that are able to
      interfere with cancer glycolysis, and on their use in specific combination
      therapies.

PMID- 30226289
TI  - A Self-Folding Polymer Film Based on Swelling Metal-Organic Frameworks.
AB  - Herein, we exploit the well-known swelling behaviour of metal-organic frameworks
      (MOFs) to create a self-folding polymer film. Namely, we show that incorporating
      crystals of the flexible MOF MIL-88A into a polyvinylidene difluoride (PVDF)
      matrix affords a polymer composite film that undergoes reversible shape
      transformations upon exposure to polar solvents and vapours. Since the self
      folding properties of this film correlate directly with the swelling properties
      of the MIL-88A crystals, it selectively bends to certain solvents and its degree
      of folding can be controlled by controlling the relative humidity. Moreover, it
      shows a shape-memory effect at relative humidity values from 60 % to 90 %. As
      proof of concept, we demonstrate that these composite films can lift cargo and
      can be used to assemble 3D structures from 2D patterns. Our strategy is a
      straightforward method for designing autonomous soft materials with folding
      properties that can be tuned by judicious choice of the constituent flexible MOF.

PMID- 30226290
TI  - Striatal presynaptic dopaminergic dysfunction in gambling disorder: A 123 I-FP
      CIT SPECT study.
AB  - Although the involvement of dopamine in gambling disorder (GD) has long been
      hypothesized, its precise role remains unclear. The action of dopamine in the
      synapses is regulated by the dopamine transporter (DAT). We hereinafter present
      significant differences between a sample of 15 treatment-seeking GD subjects and
      17 healthy controls in terms of striatal DAT availability, and we explore its
      association with reward-based decision making. We performed 123 I-FP-CIT Single
      photon emission computed tomography (SPECT) and correlated DAT binding ratios in
      the bilateral caudate and putamen with gambling symptoms (G-SAS, PG-YBOCS) and
      behaviors, as well as other psychometric variables (anhedonia and impulsivity).
      Gambling disorder (GD) subjects were also administered a computerized version of
      the Iowa gambling task (IGT) to assess reward-based decision making. We found
      reduced DAT availability in GD subjects compared with healthy controls (-13.30%
      in right caudate, -11.11% in right putamen, -11.44% in left caudate, and -11.46%
      in the left putamen). We also found that striatal DAT availability was inversely
      correlated with days spent gambling and IGT performance in GD subjects. These
      results provide evidence for a presynaptic dopaminergic dysfunction in striatal
      regions of GD subjects. Functional DAT down-regulation possibly sustains the
      transition towards compulsive gambling addiction, characterized both by
      hyperdopaminergic and hypodopaminergic states in the context of a sensitized
      dopaminergic system.

PMID- 30226291
TI  - Towards a better recording of microtubule cytoskeletal spatial organization and
      dynamics in plant cells.
AB  - Numerous fluorescent marker lines are currently available to visualize
      microtubule (MT) architecture and dynamics in living plant cells, such as markers
      expressing p35S::GFP-MBD or p35S::GFP-TUB6. However, these MT marker lines
      display obvious defects that affect plant growth or produce unstable fluorescent
      signals. Here, a series of new marker lines were developed, including the
      pTUB6::VisGreen-TUB6-expressing line in which TUB6 is under the control of its
      endogenous regulatory elements and eGFP is replaced with VisGreen, a brighter
      fluorescent protein. Moreover, two different markers were combined into one
      expression vector and developed two dual-marker lines. These marker lines produce
      bright, stable fluorescent signals in various tissues, and greatly shorten the
      screening process for generating dual-marker lines. These new marker lines
      provide a novel resource for MT research.

PMID- 30226292
TI  - Fluid-structure interaction simulations of venous valves: A monolithic ALE method
      for large structural displacements.
AB  - Venous valves are bicuspidal valves that ensure that blood in veins only flows
      back to the heart. To prevent retrograde blood flow, the two intraluminal
      leaflets meet in the center of the vein and occlude the vessel. In fluid
      structure interaction (FSI) simulations of venous valves, the large structural
      displacements may lead to mesh deteriorations and entanglements, causing
      instabilities of the solver and, consequently, the numerical solution to diverge.
      In this paper, we propose an arbitrary Lagrangian-Eulerian (ALE) scheme for FSI
      simulations designed to solve these instabilities. A monolithic formulation for
      the FSI problem is considered, and due to the complexity of the operators, the
      exact Jacobian matrix is evaluated using automatic differentiation. The method
      relies on the introduction of a staggered in time velocity to improve stability,
      and on fictitious springs to model the contact force of the valve leaflets.
      Because the large structural displacements may compromise the quality of the
      fluid mesh as well, a smoother fluid displacement, obtained with the introduction
      of a scaling factor that measures the distance of a fluid element from the valve
      leaflet tip, guarantees that there are no mesh entanglements in the fluid domain.
      To further improve stability, a streamline upwind Petrov-Galerkin (SUPG) method
      is employed. The proposed ALE scheme is applied to a two-dimensional (2D) model
      of a venous valve. The presented simulations show that the proposed method deals
      well with the large structural displacements of the problem, allowing a
      reconstruction of the valve behavior in both the opening and closing phase.

PMID- 30226293
TI  - Changes in growth, anaemia, and iron deficiency among children aged 6-23 months
      in two districts in Nepal that were part of the post-pilot scale-up of an
      integrated infant and young child feeding and micronutrient powder intervention.
AB  - There is limited research on integrated infant and young child feeding (IYCF) and
      micronutrient powders (MNPs) programmes operating at scale, despite widespread
      implementation. This study uses cross-sectional baseline (n = 2,542) and endline
      (n = 2,578) surveys representative of children 6-23 months in two districts in
      Nepal that were part of a post-pilot scale-up of a IYCF-MNP programme.
      Multivariable log-binomial regression models were used to estimate prevalence
      ratios (PRs) for stunting (length-for-age z-score <-2), wasting (weight-for
      length z-score <-2), underweight (weight-for-age z-score <-2), anaemia (altitude
      adjusted haemoglobin <110 MUg/L), moderate or severe anaemia (altitude-adjusted
      haemoglobin <100 g/L), iron deficiency (inflammation-adjusted ferritin <12
      MUg/L), and iron deficiency anaemia (iron deficiency + anaemia [IDA]) at endline
      versus baseline and also to compare children in the endline survey based on
      frequency of mothers' interactions with female community health volunteers
      (FCHVs; >1* per month or monthly vs. <1* per month) and MNP coverage (1 or >=2
      distributions vs. none among children 12-23 months). Endline children were
      significantly less likely to be stunted than baseline children in both districts
      (multivariable-adjusted PR [95% CI]: 0.77 [0.69, 0.85], P < 0.001 and 0.82 [0.75,
      0.91], P < 0.001 in Kapilvastu and Achham, respectively); however, only Achham
      had significantly lower prevalences of underweight, moderate/severe anaemia, iron
      deficiency, and IDA at endline. At endline, 53.5% and 71.4% of children had tried
      MNP in Kapilvastu and Achham districts, respectively, consuming an average of 24
      sachets from the last distribution. Frequent maternal-FCHV interactions were
      associated with a reduced risk of stunting and underweight at endline, whereas
      repeat MNP coverage was associated with reduced risk of anaemia and IDA. Future
      research using experimental designs should verify the potential of integrated
      IYCF-MNP programmes to improve children's nutritional status.

PMID- 30226294
TI  - A novel approach to the diagnosis and treatment of hemoptysis in infants: A case
      series.
AB  - INTRODUCTION: Hemoptysis in children is an uncommon presenting symptom but can be
      life-threatening if massive. Cardiac catheterization and coil embolization of
      aorto-pulmonary collateral vessels (APCs) is uncommon in pediatric hemoptysis
      patients without congenital heart disease. METHODS: We present a series of seven
      infants (<=12 months of age) with hemoptysis, all of whom underwent cardiac
      catheterization to look for and intervene upon APCs, if found. Only those
      patients who underwent both bronchoscopy as well as cardiac catheterization from
      January 1995 to January 2015 were included in this retrospective review. RESULTS:
      Seven patients met inclusion criteria, and three had a history of recurrent
      hemoptysis. The mean age was 3 months. Four had evidence of bleeding on
      bronchoscopy. All seven had respiratory distress which necessitated ICU
      admission; five required mechanical ventilation. Cardiac catheterization showed
      significant APCs (>2 mm) in six of the seven studied patients, all of which were
      coil embolized. One patient had no significant APCs and therefore, no
      embolization. All patients had complete resolution with no recurrences during the
      10-20-year outpatient follow-up period. Chest CT scans were not helpful in
      delineating the site or etiology of bleeding in any patient. CONCLUSIONS: APCs
      should be considered as a differential diagnosis for pulmonary hemorrhage in
      infants after more common causes have been ruled out.

PMID- 30226295
TI  - Inhaler screw-up: A real world cystic fibrosis (CF) case.
AB  - A 40-year-old male with Cystic Fibrosis developed a sudden onset choking, cough,
      dyspnea and hemoptysis after using his inhaler. He presented to A&E. CT scan
      located a foreign body in his right bronchus intermedius (RBI). Rigid
      bronchoscopy was performed and removed a plastic rawl plug with screw from his
      RBI. He made a rapid recovery. On questioning he mentioned he had stored his
      inhaler uncapped in the same pocket he had this screw which he found at work.
      Small objects can lodge in inhalers due to their design/mouthpiece uncapping.
      This can result in endobronchial foreign body aspiration. This case highlights
      the importance of replacing inhaler cap when not in use.

PMID- 30226296
TI  - Titration and optimization trial for the initiation of insulin glargine 100 U/mL
      in patients with inadequately controlled type 2 diabetes on oral antidiabetic
      drugs.
AB  - For patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic
      control, addition of basal insulin is recommended, but titration and optimization
      of basal insulin therapy in primary care is not well understood. We conducted an
      observational trial in 2470 patients with T2DM who initiated insulin glargine 100
      U/L (Gla-100) on top of oral antidiabetic drugs. Physicians were free to choose
      either a "Davies," "Fritsche" or "individual" titration algorithm. We found that
      fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) levels were
      effectively reduced by Gla-100; 65.9% of patients achieved the primary endpoint
      (FBG <=6.1 mmol/L (110 mg/dL) or an individual HbA1c target). There were no
      significant differences in efficacy and safety between the algorithms used. The
      mean FBG decreased by 3.2 mmol/L (59 mg/dL) over 12 months, while the mean HbA1c
      decreased by 15.3 mmol/mol (1.4%)%. From a starting dose of 11.7 U/d, the Gla-100
      dosage was 22.8 U/d at 12 months, with similar values in each group. Rates of
      hypoglycaemia were low and did not differ by titration algorithm. We conclude
      that Gla-100 was effective at reducing FBG and HbA1c, independent of the
      titration algorithm, but observed that algorithms were inconsistently applied in
      clinical practice.

PMID- 30226297
TI  - TaZIM-A1 negatively regulates flowering time in common wheat (Triticum aestivum
      L.).
AB  - Flowering time is a critical determinant of regional adaptation for crops and has
      strong effects on crop yields. Here, we report that TaZIM-A1, an atypical GATA
      like transcription factor, is a negative regulator of flowering in wheat. TaZIM
      A1 possessed weak transcriptional repression activity, with its CCT domain
      functioning as the major inhibitory region. TaZIM-A1 expression exhibited a
      typical circadian oscillation pattern under various light regimes. Overexpression
      of TaZIM-A1 caused a delay in flowering time and a decrease in thousand-kernel
      weight (TKW) in wheat under long-day conditions. Moreover, TaZIM-A1 directly
      bound to the promoters of TaCO-1 and TaFT-1 and downregulated their expression.
      Sequence analysis of a collection of common wheat cultivars identified three and
      two haplotypes for TaZIM-A1 and TaZIM-B1, respectively. Association analysis
      revealed that TaZIM-A1-HapI/-HapIII and TaZIM-B1-HapI have undergone strong
      positive selection during modern wheat breeding, likely due to their association
      with earlier heading and higher TKW. Diagnostic markers were developed for these
      haplotypes that can be used for wheat cultivar improvement, via marker-assisted
      breeding.

PMID- 30226298
TI  - Worsening of diabetic retinopathy with rapid improvement in systemic glucose
      control: A review.
AB  - Worsening of diabetic retinopathy (DR) is associated with the initiation of
      effective treatment of glycaemia in some patients with diabetes. It has been
      associated with risk factors such as poor blood-glucose control and hypertension,
      and it manifests prior to the long-term benefits of optimizing glycaemic control.
      The majority of evidence supports an association of large and rapid reductions in
      blood-glucose levels with early worsening of DR. Despite a general awareness of
      early worsening within the diabetes community, mechanisms to explain the
      phenomenon remain speculative. We provide an overview of early worsening of DR
      and its pathophysiology based on current data. We describe the phenomenon in
      various settings, including in patients receiving insulin- or non-insulin-based
      treatments, in those undergoing bariatric surgery, and in pregnant women. We
      discuss various mechanisms and theories that have been suggested to explain this
      paradoxical phenomenon, and we summarize the implications of these in clinical
      practice.

PMID- 30226299
TI  - Influence of Physical Exercise on the Dialytic Adequacy Parameters of Patients on
      Hemodialysis.
AB  - It has been suggested that physical exercise in chronic hemodialysis could
      improve dialysis dose and reduce postdialysis rebound. A randomized controlled
      trial was performed to compare a group of patients doing physical exercise during
      the first 2 h of hemodialysis sessions and another group doing physical exercise
      at home. The descriptive variables, dialysis doses measured by KtV, and rebounds
      (urea, creatinine, potassium, phosphorus), were recorded. For 69 patients: the
      mean KtV was 1.84; the 30-min rebound of creatinine was 32.37%, urea 24.39%,
      potassium 15.31%, and phosphorus 51.29%. For each patient, the basal measurement
      was compared with those determined when performing physical exercise; no
      statistically significant differences were observed between the changes
      determined to dose and rebound in the group with hemodialysis exercise compared
      to those of the home exercise group. In conclusion, performing physical exercise
      during the first 2 hours of hemodialysis sessions neither lowered postdialysis
      molecules rebound nor improved dialysis dose.

PMID- 30226300
TI  - Individualized Cool Dialysate as an Effective Therapy for Intradialytic
      Hypotension and Hemodialysis Patients' Perception.
AB  - Intradialytic hypotension (IDH) is the most common dialytic complication.
      Recurrent episodes of ischemia secondary to hemodynamic instability are
      associated with cardiomyopathy, increased risk of thrombosis of arteriovenous
      fistula, decreased quality of life, and increased mortality. Cool dialysate may
      be an effective approach to reducing intradialytic hypotension by promoting
      peripheral vasoconstriction. Most studies to date are small and do not employ
      individualized cool dialysates (ICD). The study consisted of standard and cool
      phases, with patients as their own controls. During the standard phase,
      participants underwent hemodialysis (HD) at their usual dialysate temperature at
      37 degrees C for six consecutive hemodialysis sessions. In the cool phase, the
      dialysate temperature was set at the core baseline temperature -0.5 degrees C for
      six more sessions. We compared hemodynamic parameters during the standard and
      cool phases. A total of 93 participants were included. The number of IDH episodes
      during the standard and cool phases were 3.3 +/- 2.8 and 2.0 +/- 2.2 per patient
      respectively (P < 0.001). Other hemodynamic parameters including lowest
      intradialytic mean arterial pressure were significantly increased with ICD. We
      found that there was a high baseline rate of feeling cold among all participants
      and it increased after the implementation of ICD; however, the dropout rate was
      approximately 5%. ICD is an effective tool to decrease the frequency of IDH in
      the HD population and we provide a pragmatic, real-world approach to implement
      this technique.

PMID- 30226301
TI  - Obstructive sleep apnoea and cholesterol: Independence in context.

PMID- 30226302
TI  - A Tailored Bifunctional Electrocatalyst: Boosting Oxygen Reduction/Evolution
      Catalysis via Electron Transfer Between N-Doped Graphene and Perovskite Oxides.
AB  - Fabricating perovskite oxide/carbon material composite catalysts is a widely
      accepted strategy to enhance oxygen reduction reaction/oxygen evolution reaction
      (ORR and OER) catalytic activities. Herein, synthesized, porous, perovskite-type
      Sm0.5 Sr0.5 CoO3-delta hollow nanofibers (SSC-HF) are hybridized with cross
      linked, 3D, N-doped graphene (3DNG). This rationally designed hybrid catalyst,
      SSC-HF-3DNG (SSC-HG), exhibits a remarkable enhancement in ORR/OER activity in
      alkaline media. The synergistic effects between SSC and 3DNG during their ORR and
      OER processes are firstly revealed by density functional theory calculations. It
      suggests that electron transport from 3DNG to O2 and SSC increases the activity
      of electrocatalytic reactions (ORR and OER) by activating O2 , increasing the
      covalent bonding of lattice oxygen. This electron transfer-accelerated catalysis
      behavior in SSC-HG will provide design guidelines for composites of perovskite
      and carbon with bifunctional catalysts.

PMID- 30226303
TI  - [Risk assessment indexes for shellfish poisoning outbreak caused by red tide].
AB  - OBJECTIVE: To establish the indexes and weights of risk assessment of shellfish
      poisoning outbreak caused by red tide. METHODS: The risk assessment indexes were
      developed with the methods of literature review, brainstorm and expert
      consultation, and the weights of indexes were calculated by the method of
      analytic hierarchy process. The established indexes contained the risk
      possibility, impacts of public health, population vulnerability and resilience.
      The relative risk indexes(integrated risk indexes) of different shellfish
      poisoning were computed by combining hierarchy process and TOPSIS methods.
      Moreover, the weights of indexes were further used to generate absolute risk
      values by multiplying indexes. RESULTS: Four primary indexes and 17 secondary
      indexes were identified for risk assessment of shellfish poisoning outbreak. Of
      17 secondary indexes, the knowing rate of shellfish poisoning, medical
      accessibility, the number of people being affected, laboratory testing capacity
      and the habits of eating seafood of local residents had relatively large weights
      (0.0876, 0.0840, 0.0716, 0.0703 and 0.0644, respectively), which accounted for
      nearly 38% of the total weight. All consistency ratio (CR) were less than 0.1.
      The index system was applied in Cangnan county of Zhejiang province. The results
      showed the relative risk indexes of paralytic shellfish poisoning (PSP),
      diarrhetic shellfish poisoning (DSP), neurotoxic shellfish poisoning (NSP) and
      amnesic shellfish poisoning (ASP) were 0.4526, 0.7116, 0.1657 and 0.2884, and the
      absolute risk values were 0.2542, 0.2668, 0.1907 and 0.2184, respectively. The
      risk orders of the 4 kinds of shellfish poisoning sorted by relative risk indexes
      and absolute risk values were consistent. CONCLUSIONS: The indexes and weights of
      risk assessment of shellfish poisoning outbreak caused by red tide are
      established, which can provide scientific advice for prevention and control of
      shellfish poisoning outbreak.

PMID- 30226304
TI  - [Establishment and application of public health risk assessment indexes for flood
      disaster].
AB  - OBJECTIVE: To establish a public health risk assessment indexes for flood
      disaster. METHODS: Delphi method and expert consultation were used to establish
      the public health risk assessment index system and scoring criteria, and the
      analytic hierarchy process (AHP) method was used to obtain the weight of the
      indexes. Then, the established index system was applied to evaluate the public
      health risk of the flood disaster in Anhui province, 2016. RESULTS: A public
      health risk assessment system consisting of 5 categories and 17 indexes was
      constructed. The assessment result of the flood disaster in Anhui province of
      2016 showed that the public health risk score was 0.26, suggesting that "the
      health emergency measures were effective, and the public health risks were
      effectively controlled". CONCLUSIONS: The established indexes can effectively
      assess the health risk of flood disaster and also can provide the reference for
      other disaster assessment.

PMID- 30226305
TI  - [Risk assessment for emergency events of infectious disease in outlying areas of
      large-scale activities].
AB  - OBJECTIVE: To identify and assess the potential public health risks of emergency
      events of infectious disease in the surrounding areas of Hangzhou during the 11th
      G20 summit, and to assess their impacts on the G20 summit. METHODS: The
      surrounding cities of Hangzhou included Ningbo, Wenzhou, Jiaxing, Huzhou,
      Shaoxing, Jinhua, Quzhou, Zhoushan, Taizhou and Lishui. Background information on
      infectious diseases in Zhejiang province was collected, and the brainstorming and
      expert consultation methods were used to identify the risks. The local risks and
      the impact of local risks on the G20 summit were assessed. RESULTS: The criteria
      for public health risk was first established. Through the assessments,a total of
      27 kinds of infectious diseases in 4 types of public health risks were
      identified. The impact of these risks on Hangzhou G20 summit was divided into 1
      item of high-risk, 12 items of medium risk and 14 items of low risk.According to
      the results of risk assessment, the recommendations for risk management of
      respiratory infectious diseases, intestinal infectious diseases, imported
      infectious diseases like Middle East respiratory syndrome and other infectious
      diseases were made. With risk management, Middle East respiratory syndrome was
      not occurred during the G20 summit, and the epidemic situation of other
      infectious diseases with middle or low risks was almost the same with that of
      past years. CONCLUSIONS: sThe public health risks of Hangzhou G20 summit from
      sudden infectious diseases in outlying areas are mainly medium and low risks. The
      recommendations on risk management provide a basis for reducing the adverse
      consequences of public health risks in the event of an outbreak of infectious
      diseases, avoiding the impact of various risk factors in the outlying areas on
      G20 summit.

PMID- 30226306
TI  - [Semi-quantitative risk assessment of human infection with H7N9 avian influenza
      epidemic in Zhejiang province].
AB  - OBJECTIVE: To assess the risk of local outbreaks of H7N9 avian influenza
      infection in Zhejiang province and to explore the semi-quantitative assessment
      method for public health risks in emergency. METHODS: Risk index system of human
      infection with H7N9 avian influenza caused by local transmission were reviewed.
      The weights of indexes were calculated by analytic hierarchy process, which was
      combined with the TOPSIS method to calculate the risk comprehensive index.
      RESULTS: Four primary indexes and 23 secondary indexes were identified for risk
      assessment in local outbreaks of H7N9 avian influenza infection. The weights
      ranked on the top five were:morbidity (0.0972), closure measures (0.0718),
      sterilization measures (0.0673), fatality rate (0.0651), and epidemic spread
      (0.0616). The comprehensive index of the risk of local outbreaks of H7N9 avian
      influenza ranged from high to low were Hangzhou (0.5910), Shaoxing (0.5711),
      Jiaxing (0.5199), Taizhou (0.5198), Huzhou (0.4662), Ningbo (0.3828), Wenzhou
      (0.3719), Jinhua (0.3392), Lishui (0.2727), Quzhou (0.2001) and Zhoushan
      (0.0508). CONCLUSIONS: A semi-quantitative method has been established in this
      study, which provides scientific basis for prevention and control of H7N9 avian
      influenza epidemic in Zhejiang province.

PMID- 30226307
TI  - [Establishing assessment indexes for emergency response capability of disease
      control and prevention institutions].
AB  - OBJECTIVE: To establish an emergency response capability assessment indexes for
      disease control and prevention institutions. METHODS: Health emergency response
      capability assessment indexes of Shanghai Centers for Disease Control and
      Prevention(CDCs) was drafted based upon documentary analysis, expert consultation
      and focus group discussion according to duties and features of emergency work of
      CDCs. The assessment indexes were determined by applying Delphi method (18
      experts), and the weights of indexes were determined using analytic hierarchy
      process and proportional distribution method. And then the established index
      system was used to assess the emergency response capability of CDCs in Shanghai.
      RESULTS: Two rounds of expert consultations were conducted. Kendall's coefficient
      of concordance was 0.420 and 0.495 at the first and second round of expert
      consultations respectively. After two rounds of consultations, the expert
      authority score was above 0.7. There were 7 primary indexes, 24 secondary indexes
      and 84 third-level indexes. The seven primary indexes included emergency
      management system, emergency response team, surveillance and early-warning
      ability, emergency response capacity, emergent supply capability, communication
      and cooperation, scientific research and exchange, with systematic weights of
      0.2123, 0.1754, 0.1334, 0.1916, 0.1281, 0.0962 and 0.0630,respectively. According
      to the investigation, Shanghai Municipal Center for Disease Control and
      Prevention ranked first in the total score of emergency response capability
      evaluation. CONCLUSIONS: The indexes identified in this study have good
      reliability and feasibility, and can be used in assessment of emergency response
      capability in disease prevention and control institutions.

PMID- 30226308
TI  - [Association of UCP2 rs659366 polymorphisms with the outcomes of patients after
      surgery for colorectal cancer].
AB  - OBJECTIVE: To explore the association between UCP2 rs659366 polymorphisms and the
      outcomes of patients after surgery for colorectal cancer. METHODS: The study was
      conducted among a cohort of 501 patients with primary colorectal cancer who had
      surgery in Sichuan Cancer Hospital during March 2010 and July 2013. The outcomes
      of the patients were followed up. The polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method was applied to detect UPC2
      rs659366 genotypes. The log-rank test was performed to analyze the effects of
      clinical features on patients' outcomes. The correlation between UCP2 rs659366
      polymorphisms and the outcomes of patients was analyzed using the Cox
      proportional hazard model. RESULTS: In this study, the median of follow-up time
      was 44.23(0.13-78.53)months, and 101 out of 501 (20.2%) patients failed to follow
      up. The log-rank test showed the tumor site, TNM stage, vascular invasion,
      perineural invasion and the preoperative carcino-embryonic antigen(CEA) level
      were significantly associated with the outcome of colorectal cancer (P<0.05 or
      P<0.01). The overall survival rate of patients with AA, GA and GG genotypes were
      62.7%, 69.9% and 75.5%, respectively. Multivariate analysis according to Cox
      proportional hazard model taking the GG genotype as the reference indicated that
      the AA genotype increased risks for survival of patients (HR=1.823); under the
      dominant genetic model taking GG genotype as reference, GA+AA genotypes increased
      risks for the poorer outcomes of patients (HR=1.498); the addictive genetic model
      showed that allele A increased the hazard for the poorer outcomes (HR=1.787).
      CONCLUSIONS: The UCP2 rs659366 polymorphisms are significantly associated with
      the outcome of patients with colorectal cancer.

PMID- 30226309
TI  - [Trajectory modeling for estimating the trend of human papillomavirus infection
      status among men who have sex with men].
AB  - OBJECTIVE: To investigate whether trajectory model can be used to explore the
      trend of anal human papillomavirus (HPV) infection status among HIV-negative men
      who have sex with men (MSM). METHODS: HIV-negative MSM were recruited by using
      the "snowball" method from 1st September 2016 to 30th September 2017 in Urumqi.
      The subjects were followed-up every six months since enrollment. The cell samples
      in anal canal were collected and the 37-type HPV test kits were used for
      identification and classification of HPV infection at both baseline and follow-up
      visits. Taking the cumulative number of different types of HPV as the dependent
      variable and follow-up visits as the independent variable, the trajectory model
      was established for the study subjects who completed baseline, 6 months and 12
      months follow-up. The model was used to simulate the trend of HPV infection
      status when the subjects were divided into 1, 2, 3 and 4 subgroups. Bayesian
      information criterion (BIC), log Bayes factor and average posterior probability
      (AvePP) were used to evaluate the fitting effect. RESULTS: A total of 400 HIV
      negative MSM were recruited at baseline and 187 subjects completed baseline and
      two follow-ups. The fitting effect attained best when the variation trend was
      divided into two subgroups. The first subgroup accounted for 54.5%(102/187) of
      the total, and the curve of change in HPV infection was decreasing; the second
      subgroup accounted for 45.5%(85/187) of the total, and the curve of change in HPV
      infection was increasing. CONCLUSIONS: Trajectory model can effectively
      distinguish the trend of HPV infection status in HIV-negative MSM to identify the
      high-risk group of HPV infection.

PMID- 30226310
TI  - [Parents' antibiotic use for children in Ningbo: knowledge, behaviors and
      influencing factors].
AB  - OBJECTIVE: To survey the knowledge and behaviors of antibiotic use for children
      among parents in Ningbo and to explore the influencing factors. METHODS: One
      kindergarten and one primary school were randomly selected in Yinzhou and Beilun
      District of Ningbo using stratified random cluster sampling method, respectively.
      A survey on the knowledge and behaviors of antibiotics use for children was
      conducted with a self-designed questionnaire among parents of children aged 2 to
      14 years in the sampled kindergarten and school. RESULTS: The scores of
      antibiotic use knowledge were 0-4 in 36.6%(1028/2806) of parents. In the past
      month, 56.6%(556/983) of parents self-medicated their children, including
      20.3%(113/556) medicated with antibiotics. In the past year, 48.5%(1361/2806) of
      parents stored antibiotics for children at home. Multivariate logistic regression
      analysis showed that mother, and parents with city residence, higher education
      level, higher household income, medical background, male children and younger
      children had higher antibiotic use knowledge scores(P<0.05 or P<0.01); parents
      with city residence, higher education level and medical background were more
      likely to store antibiotics at home (all P<0.01); parents with city residence and
      those store antibiotics at home were more likely to self-medicate their children
      with antibiotics (P<0.05 or P<0.01). CONCLUSIONS: sPoor knowledge and massive
      antibiotic missuse for children among parents are of great concern in Ningbo.
      Tailored health education programs are needed to improve the knowledge and
      behaviors of rational antibiotic use among parents and reduce storage of
      antibiotics at home.

PMID- 30226311
TI  - [A community-based survey on risk factors of type 2 diabetic kidney disease in
      Ningbo, China].
AB  - OBJECTIVE: To investigate the prevalence and risk factors of diabetic nephropathy
      in Ningbo Yinzhou district. METHODS: Nephropathy screening was conducted among
      patients with type 2 diabetes mellitus (T2DM) registered in Ningbo Yinzhou
      district. Demographic information, clinical examination information, diabetes
      complications and behavioral risk factors of enrolled patients were collected.
      Logistic regression model was used to identify possible risk factors for the
      occurrence of diabetic nephropathy. RESULTS: Among 10 604 T2DM patients included
      in this study, there were 3744 cases of diabetic nephropathy(35.31%). Univariate
      analysis showed that gender, age, education level, diabetes duration, glycemic
      control, hypertension, stroke, smoking and waist circumference were associated
      with diabetic nephropathy (P<0.05 or P<0.01). Multivariate logistic regression
      analysis showed that male, elders, long diabetes duration, hypertension and
      smoking were independent risk factors of diabetic nephropathy (P<0.05 or P<0.01).
      CONCLUSIONS: sDiabetic nephropathy is of high prevalence in T2DM patients. Male
      patients, elders, and those with long diabetes duration, hypertension and smoking
      habits are more likely to have diabetic nephropathy.

PMID- 30226312
TI  - [Influencing factors for high level measles antibodies among 6-15 year-old
      children in Zhejiang province].
AB  - OBJECTIVE: To determine measles antibody levels and influencing factors among
      children aged 6 to 15 years in Zhejiang province. METHODS: Blood samples were
      collected from 2069 children aged 6 to 15 years in Changxing county (Huzhou) and
      Liandu district (Lishui) of Zhejiang province. Serum level of measles IgG
      antibody was measured using ELISA, and 800 mIU/mL was applied as the cut-off
      point of high antibody level. Chi-square or trend Chi-square test was used to
      analyze difference in positive rates of high antibody level among children with
      different characters, and the factors related to high antibody level in the
      vaccinated children were analyzed using multivariate logistic regression.
      RESULTS: Among 2069 subjects, positive rate of high measles antibody level was
      36.06% (746/2069). Multivariate logistic regression showed that the high measles
      antibody level was significantly associated with age of children and the age of
      first measles vaccine inoculation. The positive rate of high measles antibody
      level decreased with age(OR=0.866, 95%CI:0.830-0.904, P<0.01), and the positive
      rate in children whose first vaccination at >= 12 months of age was higher than
      those whose first vaccination at 8 months of age(OR=0.633, 95%CI:0.498-0.805,
      P<0.01). CONCLUSIONS: In order to obtain high measles antibody level and to
      maintain high levels of population immune barrier, it is suggested that first
      dose of vaccination can be appropriately delayed in low epidemic areas, and elder
      children should have timely catch-up vaccination.

PMID- 30226313
TI  - [Screening efficiencies of obstructive sleep apnea screening scales in patients
      with acute ischemic stroke].
AB  - OBJECTIVE: To evaluate the application of various obstructive sleep apnea (OSA)
      screening scales in patients with acute ischemic stroke. METHODS: One hundred and
      two patients with acute ischemic stroke were enrolled continuously during July
      2016 and March 2017 from Sir Run Run Shaw Hospital, Zhejiang University School of
      Medicine. All patients were assessed by the same physician with various OSA
      screening scales, including Epworth scale, Berlin questionnaire, STOP-Bang
      questionnaire, SOS scale, four-variable scale and its modified version.
      Polysomnography was performed in Sleeping Disorder Center on each patient.
      According to the apnea-hypopnea index (AHI) acquired from polysomnography,
      patients were divided into moderate-severe OSA group (AHI >= 15, n=58) and normal
      mild OSA group (AHI<15, n=44). The efficiencies of the scales in identification
      of patients with moderate or severe OSA were analyzed and compared. RESULTS: The
      ROC curves showed that the four-variable scale and its modified version had
      higher area under curve (0.806 and 0.807, both P<0.01) for diagnosis of moderate
      severe OSA, and the cut-off values for Epworth scale, Berlin questionnaire, STOP
      Bang questionnaire, SOS scale, four-variable scale and its modified version were
      9, 2, 4, 15, 11, 10, respectively. The sensitivities, specificities, positive and
      negative predictive values of four-variable scale and its modified version in
      diagnosis of moderate-severe OSA were higher than those of other scales.
      CONCLUSIONS: Compared with Epworth scale, Berlin questionnaire, STOP-Bang
      questionnaire and SOS scale, the four-variable scale and its modified version are
      more effective in screening of OSA for patients with acute ischemic stroke.

PMID- 30226314
TI  - [Isoliquiritigenin can inhibit migration and invasion of human glioma stem cells
      by down-regulating matrix metalloproteinases].
AB  - OBJECTIVE: To investigate the effects of isoliquiritigenin on the migration and
      invasion of human glioma stem cells and the underlying mechanism. METHODS: The
      stem cell markers CD133 and Nestin in SHG44 human glioma stem cells were examined
      with immunofluorescence microscopy. The migration and invasion ability of glioma
      stem cells was determined by transwell method. The mRNA and protein expression of
      matrix metalloproteinase (MMP)-2 and MMP-9 were detected by real-time RT-PCR and
      Western blot, respectively. RESULTS: CD133 and Nestin were positive in SHG44
      cells. The number of migrated cells in SHG44 cells treated with 20 and 80 MUmol/L
      isoliquiritigenin for 48 h were significantly lower than that in control group
      (76+/-5 and 42+/-4 vs. 85+/-6, all P<0.01), and the number of migrated cells in
      80 MUmol/L isoliquiritigenin group was lower than that in 20 MUmol/L
      isoliquiritigenin group (P<0.01). The numbers of cells crossing through membrane
      in 20 and 80 MUmol/L isoliquiritigenin groups were 190+/-13 and 130+/-9,
      respectively, which were significantly lower than that in control group (230+/
      14, all P<0.01), and the number of crossed cells in the 80 MUmol/L
      isoliquiritigenin group was lower than that in 20 MUmol/L isoliquiritigenin group
      (P<0.01). The mRNA and protein expression levels of MMP-2 and MMP-9 were
      decreased compared with control group (P<0.05 or P<0.01), and the expression
      levels in 80 MUmol/L isoliquiritigenin group were lower than those in 20 MUmol/L
      isoliquiritigenin group (P<0.05 or P<0.01). CONCLUSIONS: Isoliquiritigenin
      exhibits antitumor effects on glioma stem cells by inhibiting cell migration and
      invasion, which may be related to the down-regulation of MMP-2 and MMP-9.

PMID- 30226315
TI  - [Identification of key pathways and drug repurposing for anaplastic thyroid
      carcinoma by integrated bioinformatics analysis].
AB  - OBJECTIVE: To identify hub genes and key pathways associated with anaplastic
      thyroid carcinoma (ATC), and to explore possible intervention strategy. METHODS:
      The differentially expressed genes (DEGs) in ATC were identified by Gene
      Expression Omnibus (GEO) combined with using R language; the pathway enrichment
      of DEGs were performed by using Kyoto Encyclopedia of Genes and Genomes (KEGG)
      and Gene Ontology (GO). The protein-protein interaction (PPI) network of DEGs was
      constructed by STRING database and visualized by Cytoscape. Furthermore, the hub
      genes and key nodes were calculated by MCODE. Finally, the drug repurposing was
      performed by L1000CDS2. RESULTS: A total of 2087 DEGs were identified. The DEGs
      were clustered based on functions and pathways with significant enrichment
      analysis, among which PI3K-Akt signaling pathway, p53 signaling pathway,
      inflammatory response, extracellular matrix organization were significantly
      upregulated. The PPI network was constructed and the most significant three
      modules and nine genes were filtered. Twenty-two potential compounds were
      repurposed for ATC treatment. CONCLUSIONS: Using integrated bioinformatics
      analysis, we have identified hub genes and key pathways in ATC, and provide novel
      strategy for the treatment of ATC.

PMID- 30226316
TI  - [Multiple risk factors prediction models for high risk population of colorectal
      cancer].
AB  - Colorectal cancer is caused by the interaction of genetic and environment
      factors. Domestic and foreign scholars have attempted to develop several
      colorectal cancer risk prediction models, in order to identity risk factors, to
      screen for high risk population and evaluate the risk of developing colorectal
      cancer, so as to provide personalized screening protocols for individuals with
      different risk, and eventually reduce the incidence and mortality rate of
      colorectal cancer. Currently, the common colorectal cancer risk prediction models
      were mainly developed based on case-control study and cohort study. Models
      developed in European and American regions and Asia (excluding China) only
      include common risk factors, while Chinese models also include hereditary factors
      on the bases of common risk factors. However, the development and verification of
      each model are mainly based on local population, whether it can be applied for
      other population need to be determined. This article reviews the development,
      validation and evaluation of the risk prediction models, in order to provide a
      basis for developing more precise risk prediction models for colorectal cancer.

PMID- 30226317
TI  - [Effect of spinal cord stimulation on myocardial ischemia/infarction].
AB  - Fatal arrhythmias, heart failure, and sudden cardiac death after myocardial
      ischemia/infarction are serious threats to human health. In recent years, studies
      have shown that spinal cord stimulation (SCS) can balance autonomic activity,
      inhibit myocardial structural remodeling, improve blood flow to ischemic
      myocardium, effectively reduce the incidence of arrhythmia, heart failure and
      sudden cardiac death after myocardial ischemia/infarction, but its specific
      mechanism has not yet been fully elucidated. The effect of SCS on cardiac
      function may be achieved by inhibiting neural remodeling, or by ameliorating
      structural remodeling and electrical remodeling. This article reviews the
      progress on the role and mechanism of SCS in myocardial ischemia/infarction.

PMID- 30226318
TI  - [Regulatory role of autophagy in development of pulmonary artery hypertension].
AB  - Pulmonary arterial hypertension (PAH) is a multi-etiological chronic disease
      characterized by a progressive elevation in pulmonary resistance and vascular
      remodeling. Its pathogenesis is complicated. Recently, emerging researches
      suggest that autophagy, as a self-protection mechanism maintaining the
      intracellular environment homeostasis in eukaryotes, participate in the
      occurrence and development of various types of PAH. Autophagy can regulate the
      survival, apoptosis of pulmonary vascular wall cells and secretion of vasoactive
      substances and inflammatory cytokines, thus influencing pulmonary vascular
      homeostasis. Some drugs based on regulating autophagy activity can effectively
      improve the prognosis of PAH. In this article, the regulatory role of autophagy
      on the development of pulmonary hypertension is reviewed to provide insight into
      PAH and its treatment.

PMID- 30226319
TI  - [Focus on pediatric rheumatic and immune diseases].

PMID- 30226320
TI  - [Research progress on phenotype and genotype of hyperphenylalaninemia].
AB  - Hyperphenylalaninemia(HPA), an autosomal recessive disease, is the most common
      inborn error of amino acid metabolism, caused by the deficiency of phenylalanine
      hydroxylase(PAH) or tetrahydrobiopterin(BH4) which induced by mutations of genes.
      The accumulation of the clinical database and genetic information will enhance
      the development of novel personalized medicine and to provide more accurate and
      timely diagnostic and therapeutic approaches for HPA. This paper summarizes the
      correlations between HPA metabolism and PAH, BH4, pathogenic genes and their
      distributions in HPA, as well as the phenotypes and genotypes of HPA, so as to
      provide reference for personalized medicine for HPA.

PMID- 30226321
TI  - [Research progress on genetic and epigenetic mechanisms in congenital heart
      disease].
AB  - Congenital heart disease (CHD) is a type of birth defects due to the abnormal
      development of heart and blood vessels during embryonic stage. Studies indicate
      that the etiology of CHD is complicated. Genetic and epigenetic mechanisms
      including chromosomal abnormalities, gene mutations, nucleic acid modifications,
      non-coding RNAs may play important roles in CHD. At present, genetic mechanisms
      such as chromosome abnormality and gene mutation have been widely used in the
      diagnosis and treatment of clinical diseases. However, the application of genetic
      and epigenetic modification in diagnosis and treatment of CHD still need further
      research. This paper reviews the relationship between chromosomal abnormality,
      gene mutation, copy number variation, epigenetic modification and the occurrence
      of CHD, which may provide a basis for further exploring the early diagnosis and
      individualized therapy of CHD.

PMID- 30226322
TI  - [Research progress on transcription factors and signal pathways involved in
      congenital esophageal atresia].
AB  - Congenital esophageal atresia is one of the serious birth defects. Identifying
      the etiology and mechanism of esophageal development can provide clues for the
      effective prevention and treatment of congenital esophageal atresia. Recent
      studies have shown that a variety of transcription factors and signaling pathways
      (including Wnt signaling pathway, bone morphogenetic protein signaling pathway,
      SHH signaling pathway, vascular endothelial growth factor signaling pathway) are
      involved in esophageal proliferation, differentiation and other processes,
      promoting the normal development of esophagus. Understanding the regulatory
      mechanisms during the normal development of esophagus can give reference for the
      prevention and treatment of congenital esophageal atresia. This article reviews
      the research progress on related transcription factors and signaling pathways in
      esophageal development.

PMID- 30226323
TI  - [Efficacy of percutaneous atrial septal defect closure guided by transesophageal
      echocardiography in children].
AB  - OBJECTIVE: To compare the efficacy of percutaneous atrial septal defect (ASD)
      closure guided by transesophageal echocardiography (TEE) or guided by fluoroscopy
      in pediatric patients. METHODS: Medical records of patients who underwent
      percutaneous ASD closure in the Children's Hospital, Zhejiang University School
      of Medicine from January 2017 to March 2018 were reviewed. There were 120
      patients whose procedures were guided by TEE (TEE group), and 125 patients who
      had their procedures guided by fluoroscopy (fluoroscopy group). The performance
      of surgery, efficacy and postoperative complications were compared between two
      groups. RESULTS: Percutaneous ASD closure was successful in all patients. The
      operation time was shorter in the TEE group than that in fluoroscopy group[(20+/
      14) min vs. (29+/-11) min, t=-7.939, P<0.05]. The size of the defect was larger
      in the TEE group than that of fluoroscopy group[(11+/-4) mm vs. (9+/-4) mm,
      t=2.512, P<0.05], but there was no significant difference in the sizes of
      occluder and occluder sheath between two groups (all P>0.05). No residual shunt,
      occluder shedding or displacement, severe arrhythmia or pericardial effusion were
      observed in either group. The incidence rates of fever, cough and diarrhea were
      not statistically different between two groups (all P>0.05). CONCLUSIONS: There
      was no significant difference in the outcome of percutaneous ASD closure guided
      by TEE or by fluoroscopy, but the procedure guided by TEE may reduce the
      operation time and can evaluate the size of ASD more accurately without involving
      radiation exposure, contrast agents use and large digital subtraction equipment.

PMID- 30226324
TI  - [Echocardiography in diagnosis of pediatric pulmonary artery sling].
AB  - OBJECTIVE: To evaluate the application of echocardiography in diagnosis of
      pediatric pulmonary artery sling. METHODS: Twenty-five children diagnosed as
      pulmonary artery sling in the Children's Hospital, Zhejiang University School of
      Medicine from July 2012 to August 2017, and 50 healthy children(control group)
      were enrolled in the study. Echocardiography was performed in all subjects. The
      origins of the left pulmonary artery(LPA) and right pulmonary artery(RPA) were
      observed; the internal diameters of LPA, RPA and main pulmonary artery(MPA) were
      measured; and the ratios of LPA/MPA and RPA/MPA were calculated. The value of
      RPA/MPA and LPA/MPA in diagnosing pulmonary artery sling was evaluated by ROC
      curve. RESULTS: Echocardiography showed that the internal diameters of RPA were
      increased in all patients; while the LPA and blood flow signals in common
      pulmonary arterial bifurcation were not found in 24 cases, in whom the MPA was
      directly extended to the RPA, and the LPA was from the massive RPA. The
      ultrasound of one special case showed that there was no distinct bifurcation of
      MPA; the MPA walked to the right and then to the left with no change in the
      internal diameter. There were significant differences in RPA/MPA(0.50+/-0.05 vs.
      0.71+/-0.15, t=7.06, P<0.01) and LPA/MPA(0.52+/-0.05 vs. 0.39+/-0.09, t=6.94,
      P<0.01) between controls and the patients. ROC curve analysis showed that the AUC
      of RPA/MPA and LPA/MPA in diagnosis of pulmonary artery sling were 0.90 and 0.89,
      respectively. When taking 0.60 as the cutoff value, the sensitivity, specificity,
      positive predictive value, negative predictive value and accuracy of RPA/MPA in
      diagnosis of pulmonary artery sling were 79%, 100%, 100%, 91% and 93%,
      respectively. When taking 0.43 as the cutoff value, the sensitivity, specificity,
      positive predictive value, negative predictive value and accuracy of LPA/MPA in
      diagnosis of pulmonary artery sling were 71%, 96%, 89%, 87% and 88%,
      respectively. CONCLUSIONS: s Echocardiography can effectively diagnose pediatric
      pulmonary artery sling. The RPA/MPA ratio of 0.60 and the LPA/MPA ratio of 0.43
      can be used as cutoff values for diagnosis.

PMID- 30226325
TI  - [Experience in treatment of complex congenital intestinal atresia in children].
AB  - OBJECTIVE: To summarize experience in the treatment of complex congenital
      intestinal atresia in children, so as to investigate the key points and effect of
      the operation. METHODS: Medical notes of 49 children with complex intestinal
      atresia treated between January 2012 and January 2018 were reviewed. The
      information of age, sex, age at operation, full-term or premature, birth weight,
      clinical manifestation, auxiliary examination, preliminary diagnosis, treatment
      process, discharge diagnosis, pathological results and prognosis of patients were
      analyzed. RESULTS: All patients underwent surgical treatment, including 42 cases
      with laparotomy (85.7%) and 7 with laparoscopic surgery (14.3%); 1 case
      undergoing laparoscopic surgery was converted to laparotomy due to meconium
      peritonitis. The mean operation time was (147+/-43) min (70-270 min); the mean
      fasting time after surgery was (8+/-3) d (4-16 d); the mean parenteral nutrition
      time was (12+/-6) d (3-30 d). Eleven cases were discharged against medical after
      operation and lost to follow-up. Among rest 38 children, 1 child (2.6%) received
      intestinal resection and ostomy five days after operation due to gastrointestinal
      perforation; 1 child (2.6%) received conservative treatment one month later due
      to adhered intestinal obstruction and left hospital with cure; 1 child (2.6%)
      received enterodialysis and ileostomy eight days after operation due to
      anastomotic leak, and received the operation for the closure of fistula after
      three months; 4 children had complications including fluid and electrolyte
      disorders, anemia, hypoproteinemia and so on, and recovered after conservative
      treatments. Postoperative follow-up showed that 1 child with duodenal atresia had
      lower body weight at 6 month after operation, but the body weight returned to
      normal when the child was one year old; 1 child with preterm labor of 32 weeks
      was treated with enteral nutrition, and gradually restored the normal diet after
      6 months. Growth retardation was not observed in other children. CONCLUSIONS:
      With active treatment and reservation of normal bowel tube as much as possible
      during the operation, the prognosis of children with complex intestinal atresia
      is usually favorable.

PMID- 30226326
TI  - [Transumbilical single-site laparoscopic surgery for congenital duodenal
      obstruction in neonates].
AB  - OBJECTIVE: To evaluate the efficacy and safety of transumbilical single-site
      laparoscopic surgery for congenital duodenal obstruction (CDO) in neonates.
      METHODS: A retrospective analysis of clinical data of 15 patients with CDO
      undergoing transumbilical single-site laparoscopic treatment during November 2017
      and January 2018 (single-site group), and 20 patients with CDO undergoing
      conventional three-hole laparoscopic treatment during August 2017 and October
      2017 (three-hole group) was performed. All patients were from the Children's
      Hospital, Zhejiang University School of Medicine. The operation time, time of
      initial feeding, time of adequate feeding, length of hospital stay after
      operation and postoperative complications were compared between two groups.
      RESULTS: The operations were completed in all patients. No patient converted to
      laparotomy, and no massive hemorrhage was observed during operation. The
      operation time of single-site group was (90+/-10) min for patients with duodenal
      diamond-shaped anastomosis and (81+/-15) min for patients with Ladd operation,
      while those of three-hole group were (85+/-9) min and (72+/-11) min,
      respectively. Postoperative initial feeding time of single-site group was (5.0+/
      1.0) d, and that of the three-hole group was (4.8+/-0.8) d. The adequate feeding
      time was (9.0+/-1.2) d in the single-site group, and (9.3+/-0.8) d in the three
      hole group. The length of hospital stay after operation was (11.2+/-2.5) d in the
      single-site group, and (11.5+/-2.8) d in the three-hole group. There was no
      significant difference in operation time, postoperative initial feeding time,
      adequate feeding time and length of hospital stay after operation between two
      groups (all P>0.05). CONCLUSIONS: Transumbilical single-site laparoscopic surgery
      for CDO in neonates is safe and effective, and the postoperative abdominal scar
      is more hidden.

PMID- 30226327
TI  - [Application of thoracoscopic surgery in repairing esophageal atresia type III
      with tracheoesophageal fistula in neonates].
AB  - OBJECTIVE: To compare the efficacy of thoracoscopic surgery versus thoracotomy in
      repairing esophageal atresia type III with tracheoesophageal fistula (EA/TEF) in
      neonates. METHODS: A retrospective analysis was conducted in 97 neonates who
      underwent EA/TEF repair between January 2012 and December 2017 in the Affiliated
      Children's Hospital of Nanjing Medical University, including 75 patients
      receiving thoracotomy and 22 patients receiving thoracoscopic surgery. The
      perioperative data and the incidence of early postoperative complications were
      compared between two groups. RESULTS: The operations were completed in all
      patients. One child (4.5%) in thoracoscopic surgery group was converted to
      thoracotomy with modified Livaditis procedure due to the long distance of two
      blind ends (>4 cm) and thinner distal end. The operation time was longer in
      thoracoscopic surgery group[(143+/-48) min vs. (120+/-40) min, P<0.05], but the
      postoperative ventilation time was shorter[(55+/-22) h vs. (65+/-19) h, P<0.05]
      and the first oral feeding was earlier in thoracoscopic surgery group[(3.2+/-1.1)
      d vs (3.9+/-1.3) d, P<0.05]. No statistical difference was observed in the ratio
      of red blood cell transfusion, length of hospital stay and drainage tube
      indwelling time between two groups (all P>0.05). The incidence of lung
      complications in thoracotomy group was higher than that in thoracoscopic surgery
      group (20.0% vs. 9.1%, P<0.01), while there were no significant differences in
      the incidence of other postoperative complications between two groups. There was
      no death in thoracoscopic surgery group, while 2 patients died in thoracotomy
      group. CONCLUSIONS: Thoracoscopic repair is a preferred surgical procedure for
      EA/TEF in neonates.

PMID- 30226328
TI  - [Endoscopic lobectomy for 47 children with pulmonary sequestration].
AB  - OBJECTIVE: To evaluate the feasibility of endoscopic lobectomy for pulmonary
      sequestration in children. METHODS: Clinical data of 47 children with pulmonary
      sequestration treated with endoscopic lobectomy from April 2015 to November 2017
      were reviewed. According to the operation date, 19 children received operation
      from April 2015 to December 2016 were early group, and 23 children received
      operation from January 2017 to November 2017 were late group (5 children with
      lesions inside diaphragm were excluded). The operation time, intraoperative blood
      loss, retention time of drainage tube, length of hospital stay and incidence of
      complications were compared between two groups. RESULTS: Among 47 children,
      endoscopic lobectomy was successfully completed in 45 children, and the rest 2
      children were converted to thoracotomy. No death was observed. The operation time
      in late group was shorter than that in the early group (P<0.05), and the
      intraoperative blood loss of the late group was less than that of early group
      (P<0.05); while there were no significant differences in retention time of
      drainage tube and length of hospital stay between two groups (both P>0.05).
      Postoperative complications occurred in 14 children, including 4 cases of
      pneumothorax, 8 cases of pleural effusion, 1 case of pulmonary infection, and 1
      case of diaphragmatic hernia. The incidence rates of postoperative complications
      in late group and early group were 17.4% (4/23) and 42.1% (8/19), and the
      difference was not statistically significant(P>0.05). During the follow-up (2-26
      months), no relapse and thoracic collapes were observed, and CT examination found
      that the remaining lungs were well compensated in all children. CONCLUSIONS: The
      endoscopic lobectomy is effective and safe with less trauma and bleeding, which
      is recommended for treatment of pulmonary sequestration in children.

PMID- 30226329
TI  - [Complications after laparoscopic Ladd operation for intestinal malrotation in
      neonates].
AB  - OBJECTIVE: To analyze complications after laparoscopic Ladd operation for
      intestinal malrotation, related causes and possible solutions. METHODS: Clinical
      data of 81 neonates who underwent laparoscopic Ladd operations for intestinal
      malrotation in the Children's Hospital, Zhejiang University School of Medicine
      between January 2015 and January 2018 were reviewed. The abdominal complications
      and findings during operation and reoperation were analyzed. RESULTS: Operations
      were successfully completed in all patients, and there was no patient converted
      to open surgery. The annular pancreas in 6 cases and duodenal diaphragm in 4
      cases were confirmed during the operation. The recurrent volvulus developed in 3
      patients (3.7%), of whom 2 cases were confirmed to have midgut necrosis during
      open surgery 1 week and 3 months after laparoscopic Ladd operation, and both
      finally died; 1 case was corrected by second laparoscopic operation. Cecal
      perforation occurred in 1 patient (1.2%), which was caused by intensive high
      frequency coagulation of the appendiceal stump. One patient (1.2%) developed
      chylous ascites and improved after conservative treatment. Adhesive small bowel
      obstruction was observed in 3 cases (3.7%), and all relieved after conservative
      treatment. CONCLUSIONS: Laparoscopic Ladd operation for intestinal malrotation in
      neonates was effective, and the incidence of abdominal complications may be
      minimized by experienced skills and strict perioperative management.

PMID- 30226330
TI  - [Thoracoscopic repair of congenital diaphragmatic hernia in neonates: a report of
      47 cases].
AB  - OBJECTIVE: To review the application of thoracoscopic repair for treatment of
      congenital diaphragmatic hernia in neonates, so as to improve the cure rate.
      METHODS: Clinical data of 47 neonates with congenital diaphragmatic hernia
      receiving thoracoscopic repair from June 2012 to June 2017 were reviewed. The
      admission age, gestational age, birth weight, timing of diagnosis, hernia
      location, clinical manifestation, surgical timing, surgical method, operation
      time, postoperative mechanical ventilation time of patients were analyzed.
      RESULTS: There were 42 cases of left diaphragmatic hernia and 5 cases of right
      diaphragmatic hernia. Thirteen cases were diagnosed prenatally. Primary
      diaphragmatic repair was successfully accomplished under thoracoscope in 45
      neonates without perioperative complications, while 2 patients were converted to
      open surgery. The average operation time was (63+/-13) min (42-150 min), the
      average blood loss was (3.0+/-1.7) mL (1.0-9.0 mL), and the average postoperative
      mechanical ventilation time was (3.9+/-1.4) d (2.0-11.0 d). Two patients died and
      the treatment was withdrawn in 3 patients with an overall cure rate of 89.4%
      (42/47). CONCLUSIONS: Thoracoscopic repair is effective and can be used as first
      choice treatment of diaphragmatic hernia in neonates.

PMID- 30226331
TI  - [Application of cameral-type three-dimensional scan in assessment of funnel
      chest].
AB  - OBJECTIVE: To evaluate the application of cameral-type three-dimensional (3D)
      scan in the assessment of funnel chest. METHODS: Eighty children with funnel
      chest were collected from the Children's Hospital, Zhejiang University School of
      Medicine during June 2016 and December 2017. All patients underwent routine CT
      scan. In the same selected mediastinal window, the lowest point of the depression
      to the front of the spine was the anteroposterior diameter (A1), and the maximum
      left to right diameter was B1 (which was perpendicular to A1). The ratio B1/A1
      was calculated to get CT Haller index (CT-HI). In the same period, the chest wall
      scan was performed by EinScan-Pro 3D scanner, and the image was analyzed by
      GeoMedic image software. On the plane of the most concave point of the sternum,
      the distance from the lowest point of the skin to the back skin was the
      anteroposterior diameter (A2), the maximum plane diameter was measured on the
      same plane (B2), and the ratio B2/A2 was the 3D-Haller index (3D-HI). Pearson
      correlation analysis was used to analyze the consistency of the two measurements.
      Kappa test was used to analyze the consistency of surgical indication based on
      cutoff value of CT-HI and 3D-HI. RESULTS: All children were able to cooperate
      with CT and 3D chest wall surface scan. The mean value of CT-HI was 3.82+/-0.96,
      and that of 3D-HI was 1.82+/-0.23. Pearson correlation analysis showed that the
      correlation coefficient between CT-HI and 3D-HI was 0.823 (P<0.01). When CT-HI >
      3.2 and 3D-HI > 1.7 were set as cutoff values for indication of operation, the
      sensitivity and specificity of 3D-HI were 90.48% and 100.0%, respectively. 3D-HI
      was well consistent with CT-HI in surgical indication (Kappa=0.801). CONCLUSIONS:
      s 3D scan can be used to assess the funnel chest in children, and 3D-HI>1.7 can
      be used as the cutoff value for surgical indication.

PMID- 30226332
TI  - [Identification of Rostellularia procumbens (L.) Nees].
AB  - OBJECTIVE: To identify the commonly used Chinese traditional herb Rostellularia
      procumbens (L.) Nees. METHODS: The appearance, morphological features and
      microscopic characteristics were adopted to identify Rostellularia procumbens
      (L.) Nees. RESULTS: Rostellularia procumbens (L.) Nees is an annual herb with
      typical spike, but without involucre bracts under inflorescence. The corolla
      appears 2 labiate lips and 2 stamens. The capsularfruit consists of 4 seeds. The
      stems of the herbs are six-ribbed and cylindrical with the lavender node.The
      oblong leaves with full margin are wrinkled and bent.The herbs are tasteless. The
      pollen grains is long-oval shaped with 2-colposate, and the pollen exine presents
      with concentrated echinate sculpture. Stomata is diacytic type with non-glandular
      hairs, and mostly consists of 3-5 cells. Glandular scales are more common and
      composed of 4 cells with intumescent and oblate head. There are numerous long
      elliptical or clavate calcium carbonate crystals (cystolith) in the stems and
      leaves, with papillary protruding. CONCLUSIONS: The appearance, morphological
      features and microscopic characteristics can be used for the quality
      identification of Rostellularia procumbens (L.) Nees.

PMID- 30226333
TI  - [Microscopic and molecular identification of pine needles].
AB  - OBJECTIVE: To identify pine needles from different plant origins by microscopic
      and molecular approaches. METHODS: The characteristics of pine needles of Pinus
      massoniana Lamb., Pinus thunbergii Parl. and Pinus armandii Franch. were
      investigated via plant morphology and microscopic characteristics. ITS2 and rbcL
      were analyzed with PCR amplification and bi-directional sequencing. MEGA 6.0 was
      used to calculate the intra-and inter-specific Kimura-2-Parameter (K2P)
      distances, and the phylogenetic tree was constructed by using the neighbor
      joining (NJ) method. RESULTS: There were significant differences in the number
      and length of pine needles, number of vascular bundles, distribution of stomatal
      lines, number and distribution of resin channels among three kinds of pine
      needles. The lengths of ITS2 sequences of Pinus massoniana Lamb., Pinus
      thunbergii Parl. and Pinus armandii Franch. were 470, 469 and 470 bp,
      respectively. The lengths of rbcL sequences in three kinds of pine needles were
      553 bp. The intraspecific variation rates of ITS2 sequences in Pinus massoniana
      Lamb., Pinus thunbergii Parl. and Pinus armandii Franch. were 0%, 0.2%, and 2.8%,
      respectively; and the intraspecific variation rates of rbcL sequences were 0%,
      2.4%, and 1.1%, respectively. There was no significant barcoding gap in
      intraspecific and interspecific genetic distances of ITS2 sequences. The
      intraspecific and interspecific distances of rbcL sequences were clearly
      separated in the barcoding gap test. The NJ tree based on rbcL showed that the
      three pine needles clustered into three separate groups, indicating that rbcL DNA
      marker could distinguish the Pinus massoniana Lamb., Pinus thunbergii Parl.,
      Pinus armandii Franch. and its close relative species. CONCLUSIONS: s The three
      types of pine needles can be distinguished accurately and rapidly by microscopic
      and molecular identification. The study provides methodology and experimental
      basis for the quality evaluation and classification of pine needles.

PMID- 30226334
TI  - [Molecular and cell biological mechanism of olfactory adaptation in
      Caenorhabditis elegans].
AB  - Olfactory adaptation is an important physiological function of animals, which can
      protect their own neurons from overstimulation, and be better to deal with all
      kinds of stimuli in the surrounding environment. In this article, we discuss the
      neuronal basis of olfactory adaptation in Caenorhabditis elegans. Up to now,
      several intracellular regulatory factors have been discovered to be associated
      with olfactory adaptation in Caenorhabditis elegans, including cyclic guanosine
      monophosphate (cGMP) signaling in the olfactory neurons AWC, OSM-9 in transient
      receptor potential vanilloid (TRPV) channel, arrestin ARR-1, diglyceride (DAG)
      pathway in G protein signaling pathways, etc. However, the neural circuits of the
      olfactory adaptation remains largely unknown. This paper reviews molecular and
      cell biological mechanism of olfactory adaptation in Caenorhabditis elegans, so
      as to provide reference for studies on olfactory sensation in advanced animals.

PMID- 30226335
TI  - [Choice of total knee arthroplasty: posterior cruciate ligament preserved or
      not].
AB  - Total knee arthroplasty is an effective method for the treatment of end-stage
      knee osteoarthrosis, which can effectively relieve joint pain and reconstruct the
      integrity of the joint. Whether the posterior cruciate ligament should be
      preserved during surgery or not, which is still in dispute. In recent years,
      posterior cruciate-retaining and substituting total knee prostheses are both
      applied in clinical practice. Both domestic and international studies have shown
      that there are no significant difference in patient satisfaction, knee flexion,
      survival rate of the prosthesis and the main clinical manifestations between two
      prostheses. However, posterior cruciate-retaining total knee prosthesis is more
      consistent with the normal physiology and biomechanics of the human body. The
      gait is more balanced and proprioceptive when walking up and down the stairs, but
      when the joints are buckling, the femur is abnormal to move back to the tibia,
      resulting in abnormal motion. While posterior cruciate-substituting total knee
      prosthesis can correct severe deformity of the knee, and keep better balance
      between flexion and extension of the knee joint, but there is a potential
      complication of patellar clunk syndrome. Therefore, under the same conditions,
      the younger patients may prefer to chose posterior cruciate-retaining total knee
      prosthesis, while elder patients may prefer to chose posterior cruciate
      substituting total knee prosthesis. This paper reviews the function of posterior
      cruciate ligament, as well as the advantages and disadvantages of two prostheses,
      so as to provide some references for clinic.

PMID- 30226336
TI  - [Research progress on exosomes in diagnosis and treatment of cardiovascular
      diseases].
AB  - Exosome is a specific subset of vesicles from intracellular origin vesicles
      containing varies of microRNAs, mRNAs, proteins and lipids. It has been
      demonstrated that contents of exosomes could be altered due to different
      physiological and pathological stress, which could be used as clinical biomarker
      to reveal the disease state. In addition, according to previous studies, exosomes
      could exert protective roles for cardiovascular diseases such as atherosclerosis,
      myocardial infarction and ischemia/reperfusion injury, etc. The aim of this
      review is to summarize current research progress on exosomes, related
      implications in diagnosis and treatment of cardiovascular diseases and
      corresponding mechanisms.

PMID- 30226337
TI  - A review of the non-equivalent control group post-test-only design.
AB  - BACKGROUND: Quantitative research designs are broadly classified as either
      experimental or quasi-experimental. The main distinguishing feature of the quasi
      experiment is the manipulation of the independent variable without randomisation.
      When randomisation or use of a control group is unfeasible, a researcher can
      choose from a range of quasi-experimental designs. AIM: To present the features
      of the quasi-experimental 'non-equivalent control group post-test-only' design,
      which aims to demonstrate causality between an intervention and an outcome.
      DISCUSSION: This paper provides an overview of the non-equivalent control group
      post-test-only design in terms of its design features, applications and
      statistical analysis, as well as its advantages and disadvantages. CONCLUSION:
      The non-equivalent control group post-test-only design can be used in natural
      settings, where randomisation cannot be conducted for ethical or practical
      reasons. Although the design is less complex than some other designs, with low
      error propagation, it is vulnerable to threats to internal validity.

PMID- 30226338
TI  - Investigating ward nurses' responses to deteriorating patients.
AB  - : Deteriorating patients often present with suboptimal vital signs. If these are
      not recognised by healthcare staff, the patient's condition can deteriorate
      further, potentially leading to serious complications and even death. Despite
      efforts to improve ward nurses' recognition of, and responses to, deteriorating
      patients, this aspect of care has been found to be suboptimal. AIM: To identify
      factors that influence ward nurses' responses to deteriorating patients. METHOD:
      A literature review was undertaken, based on the research question 'What factors
      influence the trigger component of ward-based registered nurses' afferent
      response to deteriorating patients?' Several electronic databases were searched
      electronically to identify relevant articles, alongside hand-searching. Inclusion
      and exclusion criteria were set to determine which articles should be included in
      the literature review. FINDINGS: Nine studies were identified for inclusion in
      the literature review. Four main themes that influenced ward nurses' responses to
      deteriorating patients emerged: communication, diurnal and weekend variation,
      knowledge and attitudes, and nurse staffing levels. CONCLUSION: Effective
      communication was identified as an important factor in improving ward nurses'
      responses to deteriorating patients, as was improved knowledge of 'do not attempt
      cardiopulmonary resuscitation' (DNACPR) orders. It was also identified that
      increased ward nurse numbers improved responses to deteriorating patients, as did
      increased availability of senior healthcare staff, which enabled junior staff to
      escalate care.

PMID- 30226339
TI  - Comparing low-dose bupivacaine with epidural volume extension to standard
      bupivacaine dosing for short obstetric procedures: a prospective, randomized
      study.
AB  - BACKGROUND: Intrathecal bupivacaine's long duration of action can unnecessarily
      increase the time to meet post-anesthesia care unit (PACU) discharge criteria for
      patients undergoing short obstetric procedures. We sought to use a technique
      known as epidural volume extension (EVE) to determine if we could provide an
      adequate surgical block while significantly decreasing the time required to meet
      PACU discharge criteria for patients undergoing short obstetric procedures.
      METHODS: Fifty participants were randomized into two groups. The control group
      received a 10 mg of 0.5% isobaric bupivacaine plus 15 MUg of fentanyl injection
      in the intrathecal space via a combined spinal-epidural technique. The EVE group
      received a 5 mg of 0.5% isobaric bupivacaine plus 15 MUg of fentanyl injection in
      the intrathecal space followed immediately by a 10 ml injection of sterile saline
      through the epidural needle for the EVE. RESULTS: Data were analyzed on 45 of the
      50 patients. Time to meet PACU discharge criteria was significantly reduced in
      the EVE group when compared to the control group (50 vs. 135 minutes, p<0.001).
      The EVE group had a faster time to complete motor recovery when compared to the
      control group (66 vs. 181 minutes, p<0.001). Peak block height was similar in
      both groups at the time of surgery start (T5 vs. T5, p= 0.44). CONCLUSIONS: The
      use of low-dose isobaric bupivacaine in combination with 10 ml of saline EVE
      allows for faster motor recovery and time to meet PACU discharge criteria in
      patients undergoing short obstetric procedures.

PMID- 30226340
TI  - Comparative effectiveness of pharmacologic interventions to prevent shivering
      after surgery: a network meta-analysis.
AB  - INTRODUCTION: Although many drugs have been studied to prevent postoperative
      shivering, their comparative effectiveness is unknown. We attempted to assess the
      comparative effectiveness of the pharmacologic strategies to prevent shivering
      after surgery including intravenous (IV) and intrathecal (IT) meperidine, IV and
      IT dexmedetomidine, IV and IT clonidine, nefopam, tramadol, ketamine, and
      serotonin receptor antagonists. EVIDENCE ACQUISITION: We implemented a
      frequentist network meta-analysis of randomised trials. Random effect model was
      selected according to deviance information criteria. The incidence of moderate or
      severe shivering and the overall incidence of postoperative shivering were
      compared in all patients and subgroups of general and spinal anaesthesia.
      EVIDENCE SYNTHESIS: Seventy trials with 6,062 participants were included. All
      interventions except clonidine IT and dexmedetomidine IT significantly decreased
      the incidence of moderate or severe shivering. All interventions except clonidine
      IT significantly decreased the overall incidence of shivering. Nefopam IV was
      ranked best regarding both the incidence of moderate or severe shivering (odds
      ratio [OR] 0.04, 95% confidence interval [CI] 0.04-0.25, SUCRA 86.2, moderate
      quality-evidence), and the overall incidence of shivering (OR 0.07, 95% CI 0.03
      to 0.15, SUCRA 85.7, moderate quality-evidence), which was consistent in the
      subgroups of anaesthesia. CONCLUSIONS: Nefopam was ranked best regarding both
      severity and incidence of postoperative shivering. In addition to nefopam,
      tramadol, meperidine IV and IT, and dexmedetomidine IV were ranked high. However,
      there was significant heterogeneity regarding the individual drug regimen and
      surgery type, precluding firm conclusion. Further randomized trials are required
      to compare the efficacy of the drugs with high rank.

PMID- 30226341
TI  - Evaluation of an active decision support system for hemodynamic optimization
      during elective major vascular surgery.
AB  - BACKGROUND: Active decision support systems implementing goal directed therapy
      may be an approach to reduce disparities in outcome between different health care
      providers. We assessed feasibility of and adherence to an active decision support
      system (ADSS) comprising fluids, vasopressors, and dobutamine to optimize
      hemodynamics during high-risk vascular surgery. METHODS: In this prospective
      observational trial a closed-loop goal-directed therapy protocol, employing the
      minimally-invasive LiDCOrapid device, was used to actively provide advice to the
      anesthesiologist during surgery. All given suggestions and all interventions were
      recorded. Every intervention without or against the given advice had to be
      justified. The primary outcome parameters were the number of interventions done
      according to the ADSS and its duration of use. Reasons for non- compliance served
      to describe its limitations. RESULTS: The active decision support system was
      employed in 32 patients during 137 hours. Median (IQR) use of the ADSS as
      percentage of surgery time was 100% (94% - 100%) with 743 interventions being
      executed. 634 interventions were done according to ADSS proposals. Reasons to act
      against or without advice were: hemodynamic instability (6%), foreseeing a
      surgical event (2%), medical reasons (2%), awaiting hemodynamic improvement (1%)
      and orders by senior physician or surgeons (1%). In five patients the
      anesthesiologist decided to modify intervention thresholds of the underlying
      protocol. CONCLUSIONS: High rates of compliance underline clinical acceptability
      and feasibility of this ADSS during vascular surgery. It may therefore facilitate
      the work of anesthesiologists and reduce disparities in patient outcomes due to
      different healthcare providers. Particularly, rapidly developing hemodynamic
      perturbances as well as co-factors the ADSS as of now does not anticipate are
      current limitations. These findings may serve to further improve this stand-alone
      real-time ADSS.

PMID- 30226342
TI  - Intraoperative dexmedetomidine attenuates stress responses in patients undergoing
      major spine surgery.
AB  - BACKGROUND: Surgical stress induces stress hormone release and sympathetic
      hyperactivation, resulting in hemodynamic instability. Dexmedetomidine has
      sympatholytic and hemodynamic stabilizing effects. We investigated whether
      dexmedetomidine could attenuate stress responses in major spine surgery. METHODS:
      In this prospective randomized study, 52 patients undergoing spine fusion surgery
      were randomized to placebo (n=26) or to dexmedetomidine (n=26) groups.
      Dexmedetomidine at a rate of 0.4 MUg/kg/h or saline was infused, starting
      immediately after anesthetic induction and continuing until the end of surgery.
      Anesthesia was performed using desflurane and remifentanil in both groups. Serum
      levels of cortisol, epinephrine, norepinephrine, and interleukin-6 were assessed
      before surgery (T1), at the surgical incision (T2), at the bone procedure (T3),
      and 1 hour after surgery (T4). The hemodynamic variables and the autonomic
      nervous system balance evaluated with heartrate variability were assessed at the
      same time points. RESULTS: Epinephrine and norepinephrine levels were higher over
      time in the control than in the dexmedetomidine group (P=0.001 and <0.001,
      respectively). The changes in cortisol, interleukin-6, and hemodynamics were
      similar between the groups. In the heart rate variability analysis, high
      frequency decreased and low-frequency and low-frequency/high- frequency ratio
      increased during surgery in the control group, whereas they were maintained at
      the baseline level in the dexmedetomidine group. The changes in high-frequency,
      low- frequency, and the low-frequency/high-frequency ratio over time differed
      between the groups (P=0.009, 0.024, and 0.011, respectively). CONCLUSIONS:
      Intraoperative dexmedetomidine administration reduced stress hormone release and
      maintained the balance of the autonomic nervous system. Dexmedetomidine could
      attenuate surgical stress response without untoward hemodynamic adverse events.

PMID- 30226343
TI  - Cardiac output monitoring during liver transplantation: which tool to choose?

PMID- 30226344
TI  - Organ donation after neurological or circulatory death? Two is better than one.

PMID- 30226345
TI  - Stroke volume variation and intraoperative bleeding during functional endoscopic
      sinus surgery.

PMID- 30226346
TI  - Predicting extubation success: instrumental assessment, clinical tests and cave
      diving.

PMID- 30226347
TI  - Kansas and Medicaid: New Evidence on Potential Expansion and Work Requirements.
AB  - Issue: Kansas remains one of 17 states that have not expanded Medicaid. In 2017,
      the Kansas legislature voted to expand Medicaid, but former Governor Sam
      Brownback vetoed the measure. Goal: To examine evidence on health care coverage
      and access among low-income Kansans and to review the potential impact of
      expanding Medicaid with the possible addition of a work requirement as a
      condition of eligibility. Methods: Findings from a telephone survey of 1,000 low
      income nonelderly adults in Kansas were compared with data on low-income adults
      in Ohio and Indiana, both of which expanded Medicaid. Findings and Conclusions:
      The uninsured rate among low-income Kansans ages 19 to 64 is 20 percent,
      significantly higher than rates in Ohio and Indiana. Low-income Kansans also
      reported comparatively more frequent delays in care because of cost, greater
      difficulty affording medical bills, and worse health care quality. Survey data
      show Medicaid expansion is favored by 77 percent of low-income Kansans, and state
      policymakers have expressed interest in using a Section 1115 waiver for
      expansion, which would include a work requirement. Our data suggest such a
      provision would likely have little impact on employment in Kansas, where most
      potential Medicaid enrollees are disabled or already employed.

PMID- 30226348
TI  - Net Worth, Asset Transfers, and Income Exclusions for Needs-Based Benefits. Final
      rule.
AB  - The Department of Veterans Affairs (VA) amends its regulations governing
      veterans' eligibility for VA pensions and other needs-based benefit programs. The
      amended regulations establish new requirements for evaluating net worth and asset
      transfers for pensions and identify which medical expenses may be deducted from
      countable income for VA's needs-based benefit programs. The amendments help to
      ensure the integrity of VA's needs-based benefit programs and the consistent
      adjudication of pension and parents' dependency and indemnity compensation
      claims. Lastly, the amendments effectuate: Statutory changes for pension
      beneficiaries who receive Medicaid-covered nursing home care; a statutory income
      exclusion for disabled veterans; and longstanding statutory income exclusions for
      all VA needs-based benefits.

PMID- 30226349
TI  - Pure or Primary neuritic Leprosy (PNL).

PMID- 30226350
TI  - A critical appraisal on pure neuritic leprosy from India after achieving WHO
      global target of leprosy elimination.
AB  - Background: Clinical data on pure-neuritic leprosy (PNL) is limited. Objective:
      To study the clinical and epidemiological features of PNL in the leprosy post
      elimination era. Methods: This was a retrospective analysis of the clinic records
      of leprosy patients from January 2006 to June 2013. Data regarding age, sex,
      disease duration, presenting complaints, nerves affected, complications and
      treatment received were extracted from PNL cases. Results: Among 906 registered
      leprosy cases, 48 (5.3%) were found to have PNL. The mean age was 36.9 +/- 16.2
      years and predominantly males were affected (85.4%). The mean delay between onset
      of symptoms and diagnosis was 2.1 +/- 2.2 years. Multiple nerves were affected in
      36 patients (75%) and 12 (25%) had only onenerve involved. Visible deformities at
      presentation were noted in 32 (66.7%) patients. Forty patients (83.3%) were
      treated with multi drug therapy-multibacillary (MDTMB) regimen and three (6.25%)
      were treated with MDT-paucibacillary regimen. Twenty-one patients (43.8%) were
      considered positive responders to treatment. There was no correlation between the
      duration of NFI and treatment outcome. Conclusion: PNL continues to occur in the
      post-elimination era. Grade 2 deformities are common in PNL compared to other
      leprosy patients because of delayed diagnosis and treatment. Distinct diagnosis
      and treatment guidelines andsensitisation of health care workers and physicians
      to the occurrence of PNL is the need of the day.

PMID- 30226351
TI  - High resolution sonographic examination: a newer technique to study ulnar nerve
      neuropathy in leprosy.
AB  - Objectives: A prospective case control study was conducted to calculate normal
      dimensions of ulnar nerve and study the size, echotexture and morphologic
      alterations in ulnar nerve in patients with leprosy. Methods: The study group
      included 48 patients diagnosed with leprosy on basis of clinical, bacteriologic
      and/or histopathologic evaluation. Sonographic measurements were taken at 3
      levels around elbow. The morphology and vascularity were also studied. Control
      group consisted of 60 clinically normal ulnar nerves, on whichultrasound was
      performed to calculate normal parameters. 96 Ulnar nerves were independently
      evaluated clinically and on ultrasound. The mean cross sectional area and
      diameters (both antero-posterior and mediolateral) of controls at all three
      levels were calculated. The normal sonographic dimensions of ulnar nerve were
      calculated based on Mean +/- 2SE and beyond the upper limit of normal was
      considered enlargedon ultrasound. Statistical analysis was done using SSPS
      version 17.0. Results: The dimensions of ulnar nerve were significantly larger in
      leprosy group for all levels (P value , 0.001). Sonographic abnormalities
      included hypoechoic areas (61.45%), loss of fascicular pattern (same 61.45%) and
      focal hyperechoic areas (48.95%). 37.5% of nerves (6 out of 16) with clinical
      evidence of reaction showed endoneural vascularity. Conclusions: We conclude that
      by detecting enlargement and/or morphologicalterations of ulnar nerve, sonography
      can objectively determine involvement ofulnar neuropathy in leprosy.

PMID- 30226352
TI  - Spatial distribution of leprosy in Nigeria.
AB  - Background: Despite achieving the WHO elimination target of less than 1/10,000
      population in 1998 at the national level, there are still pockets of relative
      high endemicity of leprosy in Nigeria. This study used spatial analytic
      techniques to determine the spatial distribution of leprosy in Nigeria. Methods:
      The study is an ecological study of secondary data of new leprosy cases reported
      to the National TB and Leprosy Control Programme (NTBLCP) in Nigeria, 2010-2014.
      The 36 states and Federal Capital Territory were used as the unit of geographical
      analysis. The global Moran's I and Local Moran's I (LISA) test wereused to
      measure spatial autocorrelation and significant levels were taken at P < , 0.05.
      Results: A total of 17,356 new leprosy cases were notified over 5 years (2010
      2014) in Nigeria. A majority of the cases were multi-bacillary 16,037 (92.4%)
      while 1319 (7.6%) were pauci-bacillary. A total of 1569 (9%) children were
      reported with leprosy. The leprosy case detection rate increased slightly from
      2.21/100,000 in 2010to 2.24/100,000 in 2012 and declined to 1.66/100,000
      population in 2014. Significant clustering of average annual leprosy case
      detection rate was observed in Kebbi state only, while childhood leprosy was
      significantly clustered in four states namely Sokoto, Kebbi, Rivers and Zamfara
      states. Conclusion: The study observed a significant clustering of leprosy case
      detection rate in Nigeria. The findings can serve as a useful guide to the
      national leprosy control programme for efficient use of scarce resources to
      target interventions to priority states for the elimination of leprosy in the
      country.

PMID- 30226353
TI  - Intrapatient comparison of Mycobacterium leprae by VNTR analysis in nasal
      secretions and skinbiopsy in a Brazilian leprosy endemic region.
AB  - Background: This study compares the strains of genotypes of M. leprae from nasal
      secretions (NS) and skin biopsy (SB) in the same patient, supplementing
      conventional epidemiology to gain insight into the infection of leprosy in
      Fortaleza, Brazil. Methods: The sample consisted of 38 newly diagnosed leprosy
      patients attending the National Reference Center of Dermatology Dona Libania
      (CDERM), in Fortaleza, who tested positive for M. leprae by PCR in DNA extracts
      of nasal secretions. DNA was also extracted from skin biopsy (SB) scrapings of
      each patient and used for multiplex PCR amplification of M. leprae VNTR loci. The
      number of repeats at 15 loci were determined by the fragment length analysis
      method. Results: Locus VNTR genotypes were achieved in 38 NS, and in 38 SB
      specimens.M. leprae strains differed in their genotypes in paired specimens in
      all but two of38 patients. The genotype similarity in the remainder ranged from
      53% to 87%. Conclusion: M. leprae 15 VNTR loci genotypes of paired nasal and
      biopsy skin samples from five patients were identical, while as many as seven
      loci differed in the 33 other patients. When the NS and biopsy genotypes were
      pooled and compared, it was found that there was a great variability among
      different VNTR markers. It is important to investigate other molecular markers
      suitable for typing genetic variations of the bacilli.

PMID- 30226354
TI  - TlyA protein of Mycobacterium leprae: a probable bio-marker of active infection.
AB  - The extent of pathogenicity of the mycobacterial infections depends on virulence
      factors that mediate survival inside macrophages. Virulence factors are generally
      believed to be specific for pathogenic species and mutated/non-functional in
      nonpathogenic strains. Mycobacterial TlyA can modulate the phagolysosome
      maturation pathway, immediately after entry into macrophages. Over-expression of
      open reading frame (ORF) ML1358 (tlyA) in tissues of leprosy patients by partial
      DNA chip and real time PCR analysis during active infection attracted our
      interest to explore the properties of this gene at molecular and serological
      levels, to understand its role in the host. Molecular properties were studied by
      cloning and expression of the corresponding gene in pASK-iba 43(p) expression
      vector in E. coli and bioinformatics tools while sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and ELISA were applied to
      investigate the serological significance of rTlyA protein in different clinical
      states ofleprosy. We observed that TlyA has a close relation among mycobacteria
      with specific protein domains in slow growing intracellular adapted pathogenic
      species. The presence of trans-membrane domains indicates its association to the
      cell membrane. The study revealed its highly significant sero-reactivity (P value
      , 0.001) in borderline lepromatous (BL) patients, and those with reversal
      reaction (RR) and erythemanodosum leprosum (ENL). Its role in active infection,
      association with the cell membrane, presence in pathogenic species and high sero
      reactivity, suggested the tlyA gene as a strong disease progression marker.

PMID- 30226355
TI  - Corticosteroid therapy in borderline tuberculoid leprosy patients co-infected
      with HIV undergoingreversal reaction: a clinical study.
AB  - Background: Mycobacterium leprae and HIV cause infectious diseases of great
      concern for the public health care sector worldwide. Both are especially
      worrisome diseases when patients become co-infected and exhibit the expected
      clinical exuberance. The objective of this study was to evaluate episodes of
      reversal reaction (RR) and the effect of the use of corticosteroids on the
      treatment of borderline tuberculoid leprosy patients co-infected with the human
      immunodeficiency virus (HIV). Methods: This is a retrospective cohort study in
      which the clinical manifestations of the patients and their responses to
      corticosteroid therapy were observed. Variables were analysed during and after
      multidrug therapy between the first and last days of prednisone, which occurred
      up to a maximum of 6 months after initiatingcorticosteroid therapy. Results: A
      total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of
      sensitivity and neural thickening were statistically significant while clinically
      ulcerated lesions were only observed in the co-infected group. Most patients were
      diagnosed with leprosy in the presence of RR and six patients manifested RR as
      animmune reconstitution inflammatory syndrome. On average, both groups received
      similar doses of corticosteroids (difference of 0.1 mg/kg/day).

PMID- 30226356
TI  - Lucio phenomenon of leprosy LL type on pregnancy: A Rare Case.
AB  - Introduction: Lucio phenomenon is a rare type of reaction in untreated, diffusely
      infiltrative form of lepromatous leprosy type, characterised with ulcerative type
      of skin lesions. Case: A 29 year old Indonesian female, 7th months primigravida
      with a four-month history of painful scarlet spots that darken and ulcerate on
      both of her hands and legs. The patient was experiencing fever. The patient's
      eyebrows were lost and her earlobes were thickened 3 years ago. Slit-skin smear:
      BI 6p,MI 7%. Histopathology: Lucio phenomenon. PCR detecting M. leprae DNA on
      skin lesion and amniotic fluid:positive; umbilical cord membrane and umbilical
      cord: negative. Anti-PGL-1 IgM and IgG: patient: 4,854 U/mL and 1,061 U/mL,
      respectively; 5 month-old baby: 5 U/mL and 1,724 U/mL, respectively; 1 year-old
      baby: 0 U/mL and 3 U/mL, respectively. Conclusion: Placenta is considered a
      protective barrier toward feto-maternal transmission of M. leprae. The baby had
      the passive antibody to M. leprae from the mother's blood transmitted through the
      umbilical cord as demonstrated by the presence of anti-PGL-1 IgG antibody.

PMID- 30226357
TI  - Autochthonous lepromatous leprosy in a Spanish woman with burns on both feet and
      skin lesions.
AB  - The incidence of leprosy is decreasing worldwide and it is considered a rare
      disease in developed countries. In Spain, leprosy is mainly an imported disease
      with only few autochthonous cases seen. The diagnosis is difficult because of a
      low index of suspicion and the absence of visualisation of fast-acid bacilli in
      the lesions. Here, we report an autochthonous case of leprosy diagnosed after 4
      years of evolution of skin lesions. Mechanical rupture of the biopsy helped
      finally to make the correct diagnosis of the disease.

PMID- 30226358
TI  - Strongyloides hyper infection in a steroid dependent leprosy patient.
AB  - Background: Immunosuppresion caused by corticosteroids predisposes leprosy
      patients to Strongyloides stercoralis infection which if untreated can be fatal.
      Patients acquire infection by walking barefoot in infested soils and can be
      infected for life because of the auto infective cycle of the parasite.
      Corticosteroids have precipitateddeath in more than 60% of disseminated
      strongyloidiasis cases. Objective: The aim of this article is to report a
      successfully treated case of SS infection in a low resourceleprosy hospital in
      rural India and increase awareness of the unique features of S. stercoralis and
      also to outline the important role that dermatologists and leprologists have in
      diagnosing and treating chronic strongyloidiasis, thus preventing cases of fatal
      hyperinfection. Discussion: Leprosy patients live in tropics and subtropics which
      are also endemic for SS infestation and hence are prone to develop this
      infection. Chronic strongyloidiasis does not have typical symptoms and clinical
      features. Those who have unexplained eosinophilia must be checked for the
      presence of the parasite before initiation of steroid therapy for reactions and
      neuritis. Leprosy heath workers must have the awareness and a high index of
      suspicion to diagnose disseminated SS infection. Otherwise these patients, if
      infected, may develop hyperinfection syndrome, which has a high fatality rate.

PMID- 30226359
TI  - Difficult diagnosis and challenging treatment - a report on leprosy.
AB  - Histoid leprosy is an unusual variant of lepromatous leprosy posing difficulties
      for diagnosis as well as treatment even to the experts. We report a case of a 73
      year old male from the hilly region of Nepal, who presented with multiple
      asymptomatic scrotal nodules for 3 months. Though clinical diagnoses were
      pilomatricoma and steatocystoma multiplex; histopathological examination was
      consistent with that of histoid leprosy. After 10 months, he had unusual Type 2
      lepra reaction with constitutional symptoms, perichondritis, epididymo-orchitis
      but without erythema nodosum leprosum. Two years later, his three family members
      were also affected with leprosy. Hence, this case is reported to highlight the
      diagnostic dilemma, complicated disease course and infectivity of histoid
      leprosy.

PMID- 30226360
TI  - Adaptive shortening of long flexor in patients with claw hand: A short report.
AB  - Adaptive shortening of long flexors is the common secondary impairment which can
      occur in patients with long standing claw hand, particularly in those who do not
      undergo any supervised physiotherapy programme.1 The main purpose of this short
      report is to describe the current physiotherapeutic means which are commonly
      employed for the management of long flexor tightness. This report further gives
      aninsight into the consequences of the delay in corrective surgery and ultimately
      describes the dire need for further research on this deformity.2Adaptive
      shortening of the muscles is a phenomenon which can occur for many reasons, like
      prolonged immobilisation of the of the body segment, postural imbalance, muscle
      imbalance, impaired muscle performance due to neuromuscular problems or may be
      due congenital and acquired deformity.Tightness of the muscles leads to
      limitation of joint range of motion.3 In leprosy the cause of adaptive shortening
      of the long flexors is muscle imbalance which occurs due to paralysis of the
      ulnar nerve at the elbow joint. Adaptive shortening of the muscles is a secondary
      impairment.4 Secondary impairments have multidimensional effects on the
      management of the deformity, including delay in surgery for the correction of
      deformity which in turn is responsible for the unemployment, social stigma and
      problems in social integration.5 Secondary impairment in some way or other is
      responsible for the above stated problems, but adaptive shortening of the long
      flexor (long flexor tightness) is important because sometimes months of therapy
      are required to attain full muscle length.

PMID- 30226361
TI  - Protocol for a Randomised Controlled Trial Investigating Decompression for
      Leprous Neuropathy (The DELN Protocol).
AB  - Objectives: An expert group of peripheral nerve surgeons, reconstructive
      surgeons, and immunologists who have extensive experience with Hansen's Disease
      convened to discuss the status of nerve decompression as a treatment for leprous
      neuropathy. The expert group recommended an international, multi-center
      randomised controlled trial (RCT). Subsequently, a study protocol called
      Decompression for Leprous Neuropathy (DELN) was designed and further refined by
      multiple investigators worldwide. The DELN Protocol: The DELN RCT seeks to
      determine the long-term effect of nerve decompression on sensibility, motor
      function, neuropathic pain, disability, and quality of life. The RCT would enroll
      patients with clinically diagnosed leprousneuropathy and positive Tinel signs in
      the upper and lower extremities. Patients would then be randomized to receive
      nerve decompression or not. Outcomes of interest include sensory function, motor
      function, pain, disability, and quality of life. The development of ulcers or
      amputations after surgery and the influence ofcorticosteroid therapy are also
      important outcomes that DELN seeks to determine. Conclusions: The study
      Decompression for Leprous Neuropathy (DELN) is an international, multi-center RCT
      with the potential to produce high quality data to address whether nerve
      decompression for leprous neuropathy can conclusively improve patient outcomes.
      We invite discussion from all those involved in the peripheral nerve and leprosy
      communities.

PMID- 30226362
TI  - Pseudoathetosis and ataxia - a rare presentation of multibacillary leprosy in a
      non-endemic area.

PMID- 30226363
TI  - Combinatorial Screening of Nanoclay-Reinforced Hydrogels: A Glimpse of the "Holy
      Grail" in Orthopedic Stem Cell Therapy?
AB  - Despite the promise of hydrogel-based stem cell therapies in orthopedics, a
      significant need still exists for the development of injectable microenvironments
      capable of utilizing the  regenerative potential of donor cells. Indeed, the
      quest for biomaterials that can direct stem cells into bone without the need of
      external factors has been the "Holy Grail" in orthopedic stem cell therapy for
      decades. To address this challenge, we have utilized a combinatorial approach to
      screen over 63 nanoengineered hydrogels made from alginate, hyaluronic acid, and
      two-dimensional nanoclays. Out of these combinations, we have identified a
      biomaterial that can promote osteogenesis in the absence of well-established
      differentiation factors such as bone morphogenetic protein 2 (BMP2) or
      dexamethasone. Notably, in our "hit" formulations we observed a 36-fold increase
      in alkaline phosphate (ALP) activity and a 11-fold increase in the formation of
      mineralized matrix, compared to the control hydrogel. This induced osteogenesis
      was further supported by X-ray diffraction, scanning electron microscopy, Fourier
      transform infrared spectroscopy, and energy-dispersive X-ray spectroscopy.
      Additionally, the Montmorillonite-reinforced hydrogels exhibited high
      osteointegration as evident from the relatively stronger adhesion to the bone
      explants as compared to the control. Overall, our results demonstrate the
      capability of combinatorial and nanoengineered biomaterials to induce bone
      regeneration through osteoinduction of stem cells in a natural and
      differentiation-factor-free environment.

PMID- 30226364
TI  - In Situ-Generated Volatile Precursor for CVD Growth of a Semimetallic 2D
      Dichalcogenide.
AB  - Semimetallic-layered transition-metal dichalcogenides, such as TiS2, can serve as
      a platform material for exploring novel physics modulated by dimensionality, as
      well as for developing versatile applications in electronics and thermoelectrics.
      However, controlled synthesis of ultrathin TiS2 in a dry-chemistry way has yet to
      be realized because of the high oxophilicity of active Ti precursors. Here, we
      report the ambient pressure chemical vapor deposition (CVD) method to grow large
      size, highly crystalline two-dimensional (2D) TiS2 nanosheets through in situ
      generating titanium chloride as the gaseous precursor. The addition of NH4Cl
      promoter can react with Ti powders and switch the solid-phase sulfurization
      reaction into a CVD process, thus enabling the controllability over the size,
      shape, and thickness of the TiS2 nanosheets via tuning the synthesis conditions.
      Interestingly, this semimetallic 2D material exhibits near-infrared surface
      plasmon resonance absorption and a memristor-like electrical behavior, both
      holding promise for further application developments. Our method hence opens a
      new avenue for the CVD growth of 2D metal dichalcogenides directly from metal
      powders and pave the way for exploring their intriguing properties and
      applications.

PMID- 30226365
TI  - Ultrastretchable Multilayered Fiber with a Hollow-Monolith Structure for High
      Performance Strain Sensor.
AB  - As a crucial component of data terminal acquisition devices, flexible strain
      sensor has shown promising applications in numerous fields, such as healthcare,
      bodynet, the intelligent traffic system, and the robotic system. For stretchable
      strain sensor, it remains a huge challenge to realize a fine balance of wide
      detection range and high sensitivity. Here, an electrically conductive carbon
      nanotube/thermoplastic polyurethane fiber with a multilayered, hollow, and
      monolith structure, accompanying high stretchability (up to 476% strain) and low
      density (about 0.46 g/cm3) is fabricated through a facile coaxial wet-spun
      assembly strategy. The as-prepared fibers with a designed independent sensitive
      zone and flexible supporting zone possess an ultralow percolation threshold (0.17
      wt %) and a tunable size and structure. This structure endows the fiber with a
      good integration of adequate flexibility, suitable strength, and high elongation
      at break for wearable electronics. The fiber, which is then assembled as a strain
      sensor, realizes the perfect combination of the wide sensing range (>350%
      strain), high sensitivity (gauge factor (GF) = 166.7 at 350% strain), and
      excellent working durability (>10 000 cycles). Our sensor could also detect small
      compressing deformations (0.35% N-1 at 0.025-50 N) by capturing the resistance
      change of the fiber with superior stability. The highly stretchable, light
      weight, and multilayered fiber with the designed hollow-monolith structure
      provides a new route for the preparation of high-performance wearable
      electronics.

PMID- 30226366
TI  - Screening Estrogen Receptor Modulators in a Paper-Based Breast Cancer Model.
AB  - The health risks associated with acute and prolonged exposure to estrogen
      receptor (ER) modulators has led to a concerted effort to identify and prioritize
      potential disruptors present in the environment. ER agonists and antagonists are
      identified with end-point assays, quantifying changes in cellular proliferation
      or gene transactivation in monolayers of estrogen receptor alpha expressing (ER+)
      cells upon exposure. While these monolayer cultures can be prepared, dosed, and
      analyzed in a highly parallelized manner, they are unable to predict the
      potencies of ER modulators in vivo accurately. Physiologically relevant model
      systems that better predict tissue- or organ-level responses are needed. To
      address this need, we describe here a screening platform capable of
      quantitatively assessing ER modulators in 96 chemically isolated 3D cultures.
      These cultures are supported in wax-patterned paper scaffolds whose design has
      improved performance and throughput over previously described paper-based setups.
      To highlight the potential of paper-based cultures for toxicity screens, we
      measured the potency of known ER modulators with a luciferase-based reporter
      assay. We also quantified the proliferation and invasion of two ER+ cell lines in
      the presence of estradiol. Despite the inability of the current setup to better
      predict in vivo potencies of ER modulators than monolayer cultures, the results
      demonstrate the potential of this platform to support increasingly complex and
      physiologically relevant tissue-like structures for environmental chemical risk
      assessment.

PMID- 30226367
TI  - Photoirradiation Generates an Ultrastable 8-Formyl FAD Semiquinone Radical with
      Unusual Properties in Formate Oxidase.
AB  - Formate oxidase (FOX) was previously shown to contain a noncovalently bound 8
      formyl FAD (8-fFAD) cofactor. However, both the absorption spectra and the
      kinetic parameters previously reported for FOX are inconsistent with more recent
      reports. The ultraviolet-visible (UV-vis) absorption spectrum reported in early
      studies closely resembles the spectra observed for protein-bound 8-formyl flavin
      semiquinone species, thus suggesting FOX may be photosensitive. Therefore, the
      properties of dark and light-exposed FOX were investigated using steady-state
      kinetics and site-directed mutagenesis analysis along with inductively coupled
      plasma optical emission spectroscopy, UV-vis absorption spectroscopy, circular
      dichroism spectroscopy, liquid chromatography and mass spectrometry, and electron
      paramagnetic resonance (EPR) spectroscopy. Surprisingly, these experimental
      results demonstrate that FOX is deactivated in the presence of light through
      generation of an oxygen stable, anionic (red) 8-fFAD semiquinone radical capable
      of persisting either in an aerobic environment for multiple weeks or in the
      presence of a strong reducing agent like sodium dithionite. Herein, we study the
      photoinduced formation of the 8-fFAD semiquinone radical in FOX and report the
      first EPR spectrum of this radical species. The stability of the 8-fFAD
      semiquinone radical suggests FOX to be a model enzyme for probing the structural
      and mechanistic features involved in stabilizing flavin semiquinone radicals. It
      is likely that the photoinduced formation of a stable 8-fFAD semiquinone radical
      is a defining characteristic of 8-formyl flavin-dependent enzymes. Additionally,
      a better understanding of the radical stabilization process may yield a FOX
      enzyme with more robust activity and broader industrial usefulness.

PMID- 30226368
TI  - Chemical Sensing at the Robot Fingertips: Toward Automated Taste Discrimination
      in Food Samples.
AB  - The development of robotic sensors that mimic the human sensing capabilities is
      critical for the interaction and cognitive abilities of modern robots. Though
      robotic skin with embedded pressure or temperature sensors has received recent
      attention, robotic chemical sensors have long been unnoticed due to the
      challenges associated with realizing chemical sensing modalities on robotic
      platforms. For realizing such chemically sensitive robotic skin, we exploit here
      the recent advances in wearable chemical sensor technology and flexible
      electronics, and describe chemical sensing robotic fingers for rapid screening of
      food flavors and additives. The stretchable taste-sensing finger electrochemical
      devices are printed on the robotic glove, which simulates the soft skin, and are
      integrated with a wireless electronic board for real-time data transmission. The
      printed middle, index, and ring robotic fingers allow accurate discrimination
      between sweetness, sourness, and spiciness, via direct electrochemical detection
      of glucose, ascorbic acid, and capsaicin. The sweet-sensing ability has been
      coupled with a caffeine-sensing robotic finger for rapid screening of the
      presence of sugar and caffeine in common beverages. The "sense of taste"
      chemically sensitive robotic technology thus enables accurate discrimination
      between different flavors, as was illustrated in numerous tests involving a wide
      range of liquid and solid food samples. Such realization of advanced wearable
      taste-sensing systems at the robot fingertips should pave the way to automated
      chemical sensing machinery, facilitating robotic decision for practical food
      assistance applications, with broad implications to a wide range of robotic
      sensing applications.

PMID- 30226369
TI  - Nicotinamide N-Methyltransferase Interacts with Enzymes of the Methionine Cycle
      and Regulates Methyl Donor Metabolism.
AB  - Methyl donor balance is critical for epigenetic regulation in cells and is
      maintained by the so-called methionine cycle proteins that regenerate S
      adenosylmethionine (SAM), the universal methyl donor, from homocysteine formed by
      the activity of methyltransferases. Nnmt is a liver enzyme that methylates
      nicotinamide, but its role in regulating methyl donor balance in the liver is
      unclear. In this study, we assessed the effect of altered Nnmt expression on
      various aspects of methyl donor metabolism in the liver. We found that Nnmt
      overexpression decreased SAM levels and the SAM/ S-adenosylhomocysteine (SAH)
      ratio both in vivo and in vitro. Nnmt knockdown did not change methyl donor
      balance in mouse primary hepatocytes but increased SAM levels and the SAM/SAH
      ratio when Gnmt, the dominantly expressed methyltransferase in liver, was
      simultaneously knocked down. Paradoxically, expression of enzymatically deficient
      Nnmt increased the SAM/SAH ratio, suggesting that Nnmt can regulate methyl donor
      balance independent of its methyltransferase activity. Proteomics analysis of
      Nnmt-interacting proteins in the liver identified Bhmt, Mat1a, and Ahcy, all
      components of the methionine cycle, and functional experiments showed that mutant
      Nnmt increased the level of remethylation of homocysteine to SAM. In summary, we
      show that the function of Nnmt in hepatic methyl donor balance is multifactorial.
      On one hand, Nnmt decreases methyl donor balance, consistent with its activity as
      a methyltransferase consuming methyl donors. On the other hand, by co-opting the
      enzymes of the methionine cycle, Nnmt aids the recycling of homocysteine to SAM
      for another round of methylation.

PMID- 30226370
TI  - Preparation of a New Type of Black TiO2 under a Vacuum Atmosphere for Sunlight
      Photocatalysis.
AB  - Black TiO2 as a solar-driven photocatalyst has attracted enormous attention from
      scientists and engineers in water and wastewater treatment field. Most of the
      methods used for the preparation of black TiO2 are thermal treatment under a
      hydrogen atmosphere. Nevertheless, it is well known that working with hydrogen is
      not safe and needs special maintenance. Here, for the first time, we prepared
      black TiO2 by sintering P25 pellets at different temperatures (500-800  degrees
      C) under a vacuum atmosphere that showed the same performance with the prepared
      black TiO2 under a hydrogen atmosphere. The samples were characterized by X-ray
      diffraction, Raman spectra field emission scanning electron microscopy,
      transmission electron microscopy, electron paramagnetic resonance, X-ray
      photoelectron spectroscopy, and ultraviolet-visible deep resistivity sounding
      techniques. The differences between the formation of oxygen vacancy density and
      color turning in sintered powder and pellet were also studied. The results showed
      that the color of the P25 powder became darker after sintering but not completely
      turning to black, whereas the P25 pellets completely turned black after
      sintering. The resultant black TiO2 was used for the photocatalytic degradation
      of the acetaminophen (ACE) in aqueous solution under AM 1.5G solar light
      illumination; it was found that the P25 pellet sintered in 500  degrees C had the
      highest photocatalytic performance for ACE degradation under AM 1.5G solar light
      illumination. The photocatalytic activity of prepared black TiO2 under vacuum and
      hydrogen atmospheres was also compared together; the results showed that
      photocatalytic activities of both samples were so close together. The existence
      of the oxygen vacancy after 6 months and long and short-term stability (by
      application for photocatalytic degradation of ACE in an aqueous solution) of the
      black TiO2 pellets was also studied; the results showed that the TiO2 pellets in
      aqueous phase had acceptable stability.

PMID- 30226371
TI  - A Nonheme FeII/2-Oxoglutarate-Dependent Oxygenase Catalyzes a Double Bond
      Migration within a Dimethylallyl Moiety Accompanied by Hydroxylation.
AB  - Prenylation of cyclodipeptides contributes largely to the structure
      diversification and biological activity. The prenylated products can be further
      metabolized by modifications like hydroxylation with cytochrome P450 enzymes or
      nonheme FeII/2-oxoglutarate-dependent oxygenases. Herein, we cloned and
      overexpressed NFIA_045530 from Neosartorya fischeri, which shares high sequence
      similarity with the nonheme FeII/2-oxoglutarate-dependent oxygenase FtmOx1Af from
      Aspergillus fumigatus on the amino acid level. FtmOx1Af is a member of the
      biosynthetic enzymes for fumitremorgin-type mycotoxins and catalyzes the
      conversion of fumitremorgin B to verruculogen by insertion of an oxygen molecule
      into the two prenyl moieties. The recombinant protein EAW25734 encoded by
      NFIA_045530 was purified to apparent homogeneity and then was used for incubation
      with intermediates of the fumitremorgin biosynthetic pathway. LC-MS analysis
      revealed no consumption of fumitremorgin B but good conversion with its
      biosynthetic precursor tryprostatin B in the presence of FeII and 2-oxoglutarate.
      Structure elucidation confirmed 22-hydroxylisotryprostatin B and 14alpha, 22
      dihydroxylisotryprostatin B as the major enzyme products. Further detailed
      biochemical characterization led to the identification of a novel enzyme, which
      catalyzes a double bond migration within the dimethylallyl moiety of tryprostatin
      B with concomitant hydroxylation. Incubation with 18O2-enriched atmosphere
      confirmed O2 as the major origin of the hydroxyl groups. Solvent exchange was
      also observed for that at C22. LC-MS analysis confirmed the presence of 22
      hydroxylisotryprostatin B in a Neosartorya fischeri extract, highlighting the
      role of this enzyme in the metabolism of intermediates of the
      fumitremorgin/verruculogen pathway. A plausible reaction mechanism implementing a
      radical rearrangement prior to accepting a hydroxyl radical from FeIII is
      discussed.

PMID- 30226372
TI  - Two Keggin-Based Isostructural POMOF Hybrids: Synthesis, Crystal Structure, and
      Catalytic Properties.
AB  - In this work we synthesized two novel isostructural twin hybrids Comp1:
      [H(C10H10N2)Cu2][PMo12O40] & Comp2: [H(C10H10N2)Cu2][PW12O40], based on the
      Keggin ions (PMo12O40-3 & PW12O40-3), Cu(I) cation, and 4,4'-bipyridine, by in
      situ hydrothermal reduction of Cu, facilitated through extensive standardizations
      of synthetic pH conditions. Both compounds crystallized in monoclinic P21/ c
      space group with similar lattice parameters and crystal structures. The
      structural similarity prompted us to explore comparative catalytic properties of
      the hybrids, to understand the relative role of the POM species in the activity.
      While characterization techniques like powder X-ray diffraction (XRD), single
      crystal XRD, IR, adsorption studies, etc. confirmed the identical structural
      hierarchy in the twin polyoxometalate-based metal organic frameworks (POMOFs),
      critical analyses through X-ray photoelectron spectroscopy, X-ray absorption near
      edge structure spectroscopy, and magnetic property studies elucidated the
      electronic and local structural properties of the two. The hybrids were highly
      active for heterogeneous catalysis of small-molecule oxidation, with Comp 2
      showing better activity than Comp1, particularly for oxidation of ethylbenzene
      and cyclooctene. Comp2 also outperformed Comp1 in photocatalytic degradation of
      methylene blue, with higher conversion efficiency of 83% and one order higher
      apparent rate constant of 0.0139 min-1, which is comparable to that of the well
      known photocatalyst, P25. Electrochemical pseudocapacitance studies revealed that
      these POMOFs are having the potential to act as good charge storage and
      conducting devices if their electrochemical stability can be improved.

PMID- 30226373
TI  - Heterostructured Silk-Nanofiber-Reduced Graphene Oxide Composite Scaffold for SH
      SY5Y Cell Alignment and Differentiation.
AB  - Stem cell therapy is promising for treating traumatic injuries of the central
      nervous system, where a major challenge is to effectively differentiate neural
      stem cells into neurons with uniaxial alignment. Recently, controlling stem cell
      fate by modulating biophysical cues (e.g., stiffness, conductivity, and patterns)
      has emerged as an attractive approach. Herein, we report a new heterostructure
      composite scaffold to induce cell-oriented growth and enhance the neuronal
      differentiation of SH-SY5Y cells. The scaffold is composed of aligned
      electrospinning silk nanofibers coated on reduced graphene paper with high
      conductivity and good biocompatibility. Our experimental results demonstrate that
      the composite scaffold can effectively induce the oriented growth and enhance
      neuronal differentiation of SH-SY5Y cells. Our study develops a novel scaffold
      for enhancing the differentiation of SH-SY5Y cells into neurons, which holds
      great potential in the treatment of neurological diseases and injuries.

PMID- 30226374
TI  - Trophic Strategies Influence Metal Bioaccumulation in Detritus-Based, Aquatic
      Food Webs.
AB  - Metal accumulation in aquatic food webs is mediated by physiochemical parameters
      of the environment and organismal traits. Trophic strategies influence an
      organisms' exposure to metal pollution, but links between trophic ecology and
      exposure to divalent metals are relatively understudied. While organically bound
      metals are typically considered unavailable for uptake, organisms directly
      consuming dissolved organic carbon (DOC) and bacteria-via the microbial loop-must
      also be consuming organically bound metals. Hence, we predicted animals feeding
      within the microbial loop would accumulate metals through their diet. To test
      this prediction, we exploited dietary differences between two organisms, Simulium
      vittatum, a filter-feeding black fly and Hyalella azteca, a shredding
      detritivore. We exposed both species to three treatments of DOC (labile,
      recalcitrant, and no additional DOC) that were crossed with exposure to variable
      copper (Cu) concentrations (2-14 MUg L-1) in laboratory microcosms. As predicted,
      H. azteca experienced a buffering effect by DOC. However, this pattern was not
      apparent for S. vittatum. Our results highlight the importance of considering
      trophic strategies when examining the impacts of metal pollution on aquatic
      communities, and demonstrate the potential for the microbial loop to facilitate
      metal uptake in freshwater food webs.

PMID- 30226375
TI  - The Intrinsic Stability of Metal Ion Complexes with Nanoparticulate Fulvic Acids.
AB  - The electrostatic contributions to metal ion binding by fulvic acids (FAs) are
      characterized in light of recent theoretical developments on description of the
      net charge density of soft nanoparticles. Under practical electrolyte
      concentrations, the radius of the small, highly charged soft nanoparticulate FAs
      is comparable to the electrostatic screening length and their electric potential
      profile has a bell shape that extends into the surrounding aqueous medium.
      Consequently, accumulation of counterions in the extraparticulate zone can be
      significant. By comparison of experimentally derived Boltzmann partitioning
      coefficients with those computed on the basis of (i) the structural FA particle
      charge and (ii) the potential profile for a nanoparticulate FA entity
      equilibrated with indifferent electrolyte, we identify the thickness of the
      extraparticulate counter charge accumulation shell in 1-1 and 2-1 electrolytes.
      The results point to the involvement of counterion condensation phenomena and
      call into question the approaches for modeling electrostatic contributions to ion
      binding that are invoked by popular equilibrium speciation codes. Overall, the
      electrostatic contributions to Cdaq2+ and Cuaq2+ association with FA are weaker
      than those previously found for much larger humic acids (HA). The intrinsic
      chemical binding strength of CdFA is comparable to that of CdHA, whereas CuFA
      complexes are weaker than CuHA ones.

PMID- 30226376
TI  - Cost optimization of osmotically assisted reverse osmosis.
AB  - We develop a nonlinear optimization model to identify minimum cost designs for
      osmotically assisted reverse osmosis (OARO), a multi-staged membrane-based
      process for desalinating high salinity brines. The optimization model enables
      comprehensive evaluation of a complex process configuration and operational
      decision space that includes nonlinear process performance and implicit
      relationships between membrane stages, saline sweep cycles, and make-up, purge,
      and recycle streams. The objective function minimizes cost, rather than energy or
      capital expenditures, to accurately account for the tradeoffs in capital and
      operational expenses inherent in multi-staged membrane processes. Generally, we
      find that cost-optimal OARO processes minimize the number of stages, eliminate
      the use of saline make-up streams, purge from the first sweep cycle, and
      successively decrease stage membrane area and sweep flowrates. The optimal OARO
      configuration for treating feed salinities of 50-125 g/L total dissolved solids
      to a water recovery of 30-70% results in process costs less than or equal to $6
      per m3 of product water. Sensitivity analysis suggests that future research to
      minimize OARO costs should focus on minimizing the membrane structural parameter
      while maximizing the membrane burst pressure and reducing the membrane unit cost.

PMID- 30226377
TI  - Biochemical Characterization of the Mycobacterium smegmatis Threonine Deaminase.
AB  - The biosynthesis of branched-chain amino acids or BCAAs (l-isoleucine, l-leucine,
      and l-valine) is essential in eubacteria, but mammals are branched-chain amino
      acid auxotrophs, making the enzymes in the pathway excellent targets for
      antibacterial drug development. The biosynthesis of l-isoleucine, l-leucine, and
      l-valine is very efficient, requiring only eight enzymes. Threonine dehydratase
      (TD), a pyridoxal 5'-phosphate (PLP)-dependent enzyme encoded by the ilvA gene,
      is the enzyme responsible for the conversion of l-threonine (l-Thr) to alpha
      ketobutyrate, ammonia, and water, which is the first step in the biosynthesis of
      l-isoleucine. We have cloned, expressed, and biochemically characterized the
      reaction catalyzed by Mycobacterium smegmatis TD (abbreviated as MsIlvA) using
      steady-state kinetics and kinetic isotope effects. We show here that in addition
      to l-threonine, l-allo-threonine and l-serine are also used as substrates by TD,
      and all exhibit sigmoidal, non-Michaelis-Menten kinetics. Curiously, beta-chloro
      l-alanine was also a substrate rather than an inhibitor as expected. The
      enzymatic activity of TD is sensitive to the presence of allosteric regulators,
      including the activator l-valine or the end product feedback inhibitor of the
      BCAA pathway in which TD is involved, l-isoleucine. Primary deuterium kinetic
      isotopes are small, suggesting Calpha proton abstraction is only partially rate
      limiting. Solvent kinetic isotopes were significantly larger, indicating that a
      proton transfer occurring during the reaction is also partially rate-limiting.
      Finally, we demonstrate that l-cycloserine, a general inhibitor of PLP-dependent
      enzymes, is an excellent inhibitor of threonine deaminase.

PMID- 30226378
TI  - Aiming to Miss a Moving Target: Bromo and Extra Terminal Domain (BET) Selectivity
      in Constrained ATAD2 Inhibitors.
AB  - ATAD2 is a cancer-associated protein whose bromodomain has been described as
      among the least druggable of its class. In our recent disclosure of the first
      chemical probe against this bromodomain, GSK8814 (6), we described the use of a
      conformationally constrained methoxy piperidine to gain selectivity over the BET
      bromodomains. Here we describe an orthogonal conformational restriction strategy
      of the piperidine ring to give potent and selective tropane inhibitors and show
      structural insights into why this was more challenging than expected. Greater
      understanding of why different rational approaches succeeded or failed should
      help in the future design of selectivity in the bromodomain family.

PMID- 30226379
TI  - Lewis-Base-Catalyzed [1 + 2 + 2] Annulation Reaction of Morita-Baylis-Hillman
      Carbonates with Unsaturated Pyrazolones: Construction of All-Stereogenic Carbon
      Cyclopentane-Fused Dispiropyrazolones.
AB  - The first Lewis-base-catalyzed unexpected [1 + 2 + 2] annulation reaction between
      Morita-Baylis-Hillman carbonates and unsaturated pyrazolones was developed. The
      multicyclic cyclopentane-fused dispiropyrazolone constructions containing five
      contiguous stereogenic centers, including two spiro quaternary centers, were
      prepared with excellent yields (81-98%) and moderate to good
      diastereoselectivities (1:1 to 13:1). Further transformation and gram-scale
      operations were also achieved efficiently.

PMID- 30226380
TI  - Intermediates and Mechanism in Iron-Catalyzed Cross-Coupling.
AB  - Iron-catalyzed cross-coupling reactions have attracted significant research
      interest, as they offer numerous favorable features compared with cross-coupling
      reactions with precious metal catalysis. While this research has contributed to
      an empirical understanding of iron-catalyzed cross-coupling, the underlying
      fundamental mechanisms of reaction and structures of catalytically active species
      have remained poorly defined. The lack of such detail can be attributed to the
      difficulties associated with studying such iron-catalyzed reactions, where
      unstable paramagnetic intermediates abound. Recently, the combined application of
      physical-inorganic spectroscopic methods, concomitant organic product analysis,
      and air- and temperature-sensitive inorganic synthesis has yielded the most
      detailed insight currently available on reactivity and mechanism in iron
      catalyzed cross-coupling. This Perspective highlights this approach and the
      limitations of the contributing techniques as well as some of the key features of
      the catalytic reactions studied and lessons learned.

PMID- 30226381
TI  - Application of Virtual Screening to the Identification of New LpxC Inhibitor
      Chemotypes, Oxazolidinone and Isoxazoline.
AB  - This report summarizes the identification and synthesis of novel LpxC inhibitors
      aided by computational methods that leveraged numerous crystal structures. This
      effort led to the identification of oxazolidinone and isoxazoline inhibitors with
      potent in vitro activity against P. aeruginosa and other Gram-negative bacteria.
      Representative compound 13f demonstrated efficacy against P. aeruginosa in a
      mouse neutropenic thigh infection model. The antibacterial activity against K.
      pneumoniae could be potentiated by Gram-positive antibiotics rifampicin (RIF) and
      vancomycin (VAN) in both in vitro and in vivo models.

PMID- 30226382
TI  - On the Reproducibility of Early-Stage Thermally Induced and Contact-Stir-Induced
      Protein Aggregation.
AB  - Is aggregation kinetics for a protein under given conditions reproducible? Is
      aggregation inherently deterministic, stochastic, or even chaotic? Because
      protein aggregation in ex vivo formulations is complex, with many origins and
      manifestations, the question of aggregation reproducibility for a given protein,
      formulation, and stressor is of both fundamental and practical significance. This
      work concerns temperature-induced and contact-stir-induced aggregation of bovine
      serum albumin (BSA) and a monoclonal antibody (mAbX). It assesses reproducibility
      via early-stage aggregation rates (ARs) from light scattering. "Global stressors"
      affect the entire protein population, for example, temperature. "Local stressors"
      affect only a partial population at a given instant, for example, stirring. The
      instrumental error distribution (IED) allows stochasticity to be identified for
      AR distributions (ARDs) broader than IED. For ARD at the limit of the IED, the
      behavior is "minimally stochastic" or "operationally deterministic." A stochastic
      index is defined in terms of the ratio of the standard deviation (SD) of log(AR)
      data and the SD of IED. Thermal aggregation was operationally deterministic for
      BSA and mAbX, although significant lot-to-lot variations for BSA were found. ARD
      from contact-stir-stress was stochastic for BSA and mAb. Despite this, log(AR)
      decreases logarithmically with rpm. These trends may hold for other global and
      local stressors.

PMID- 30226383
TI  - Classification of Epigenetic Biomarkers with Atomically Thin Nanopores.
AB  - We use the electronic properties of 2D solid-state nanopore materials to propose
      a versatile and generally applicable biosensor technology by using a combination
      of molecular dynamics, nanoscale device simulations, and statistical signal
      processing algorithms. As a case study, we explore the classification of three
      epigenetic biomarkers, the methyl-CpG binding domain 1 (MBD-1), MeCP2, and gamma
      cyclodextrin, attached to double-stranded DNA to identify regions of hyper- or
      hypomethylations by utilizing a matched filter. We assess the sensing ability of
      the nanopore device to identify the biomarkers based on their characteristic
      electronic current signatures. Such a matched filter-based classifier enables
      real-time identification of the biomarkers that can be easily implemented on
      chip. This integration of a sensor with signal processing architectures could
      pave the way toward the development of a multipurpose technology for early
      disease detection.

PMID- 30226384
TI  - Host Cell Proteome of Physcomitrella patens Harbors Proteases and Protease
      Inhibitors under Bioproduction Conditions.
AB  - Host cell proteins are inevitable contaminants of biopharmaceuticals. Here, we
      performed detailed analyses of the host cell proteome of moss ( Physcomitrella
      patens) bioreactor supernatants using mass spectrometry and subsequent
      bioinformatics analysis. Distinguishing between the apparent secretome and
      intracellular contaminants, a complex extracellular proteolytic network including
      subtilisin-like proteases, metallo-proteases, and aspartic proteases was
      identified. Knockout of a subtilisin-like protease affected the overall
      extracellular proteolytic activity. Besides proteases, also secreted protease
      inhibiting proteins such as serpins were identified. Further, we confirmed
      predicted cleavage sites of 40 endogenous signal peptides employing an N
      terminomics approach. The present data provide novel aspects to optimize both
      product stability of recombinant biopharmaceuticals as well as their maturation
      along the secretory pathway. Data are available via ProteomeXchange with
      identifier PXD009517.

PMID- 30226385
TI  - Vibrational Modes and Phonon and Thermodynamic Properties of the Metaboric Acid
      Polymorphs alpha-, beta-, and gamma-(BOH)3O3 within a Density Functional Theory
      Framework.
AB  - A combined study of vibrational and thermodynamic properties of metaboric acid
      (BOH)3O3 crystal polymorphs alpha, beta, and gamma were obtained through density
      functional theory (DFT) calculations in an attempt to resolve the conflicting
      assignments that currently exist in the literature for them. A complete
      correlation between the normal-mode assignment and vibrational signatures to
      distinguish particular features of each metaboric acid polymorph, in particular,
      those related to motions of the planar layers in alpha-(BOH)3O3, with a level of
      detail surpassing essays based on previous published experimental works has been
      achieved. Besides, no DFT-based research work was published early on the (BOH)3O3
      polymorph vibrational properties, and our DFT-simulated infrared and Raman
      spectra for all metaboric acid polymorphs agree very well with experiment.
      Comparison of the previously published experimental IR and Raman spectroscopic
      results with predictions from higher levels DFT calculations allows
      identification of the in-plane and out-of-plane B-O bending modes. For example,
      the strongest measured (DFT-calculated) Raman modes of alpha-(BOH)3O3 at 591 and
      797 cm-1 (599 and 810 cm-1) are identified as vibrational signatures of breathing
      B3O3/Ag in-plane modes, while the shoulder in the lattice modes region at 135
      (143) cm-1 is the vibrational signature of the bending B3O3/B1g out-of-plane
      mode. Phonon-dispersion bands and their respective phonon densities of states
      were also evaluated for each system, as well as temperature-dependent curves for
      entropy, enthalpy, free energy, heat capacity, and Debye temperature. Phonon
      dispersion curves are singular for each (BOH)3O3 species, and a consistent gap
      decrease between the lowest and highest frequency vibrational bands was observed.
      The DFT-based calculations also revealed that the noncovalent interactions
      prevalent in the alpha and beta crystals lead to significant differences with
      respect to the thermodynamic properties in comparison with the gamma phase.

PMID- 30226386
TI  - Salt-Induced, Continuous Deposition of Supramolecular Iron(III)-Tannic Acid
      Complex.
AB  - One-step assembly of iron(III)-tannic acid (Fe3+-TA) complex forms nanothin (~10
      nm) films on various substrates within minutes. In this deposition scheme,
      however, the film does not grow continuously over time even though Fe3+-TA
      complex is still abundant in the coating solution. In this paper, we report that
      the salt addition dramatically changes the one-off coating characteristic to
      continuous one, and each salt has its optimum concentration ( CMFT) that produces
      maximum film thickness. For detailed investigation of the salt effects, we
      employed various salts, including LiCl, NaCl, KCl, CaCl2, SrCl2, BaCl2, NaBr, and
      NaNO3, and found that only cations played an important role in the continuous
      deposition of the Fe3+-TA complex, with smaller CMFT values for the cations of
      higher valency and larger size. On the basis of the results, we suggested that
      the positively charged cations screened the negative surface charges of Fe3+-TA
      complex particles, leading to coagulation and continuous deposition, further
      supported by the zeta-potential measurement and time-resolved dynamic light
      scattering analysis.

PMID- 30226387
TI  - Cell Type and Nuclear Size Dependence of the Nuclear Deformation of Cells on a
      Micropillar Array.
AB  - While various cellular responses to materials have been published, little
      concerns the deformation of cell nuclei. Herein we fabricated a polymeric
      micropillar array of appropriate dimensions to trigger the significant self
      deformation of cell nuclei and examined six cell types, which could be classified
      into cancerous cells (Hela and HepG2) versus healthy cells (HCvEpC, MC3T3-E1,
      NIH3T3, and hMSC) or epithelial-like cells (Hela, HepG2, and HCvEpC) versus
      fibroblast-like cells (MC3T3-E1, NIH3T3, and hMSC). While all of the cell types
      exhibited severe nuclear deformation on the poly(lactide- co-glycolide) (PLGA)
      micropillar array, the difference between the epithelial-like and fibroblast-like
      cells was much more significant than that between the cancerous and healthy
      cells. We also examined the statistics of nuclear shape indexes of cells with an
      inevitable dispersity of nuclear sizes. It was found that larger nuclei favored
      more significant deformation on the micropillar array for each cell type. In the
      same region of nuclear size, the parts of the epithelial-like cells exhibited
      more significant nuclear deformation than those of the fibroblast-like cells.
      Hence, this article reports the nuclear size dependence of the self-deformation
      of cell nuclei on micropillar arrays for the first time and meanwhile strengthens
      the cell-type dependence.

PMID- 30226388
TI  - Cation-Induced Molecular Switching Based on Reversible Modulation of Peptoid
      Conformational States.
AB  - Peptoids are oligomers of N-substituted glycines with predictable folding and
      strong potentials as guest-binding receptor molecules. In this contribution, we
      investigate the structural features of a series of designed symmetric cyclic
      octamer peptoids (with methoxyethyl/propargyl side chains) as free hosts and
      reveal their morphologic changes in the presence of sodium and alkylammonium
      guests as tetrakis[3,5-bis(trifluoromethyl)phenyl]borate salts, reporting the
      first case of reversible adaptive switching between defined conformational states
      induced by cationic guests (Na+ and benzylammonium ion) in the peptoid field. The
      reported results are based on 1H NMR data, theoretical models, and single-crystal
      X-ray diffraction analysis. They represent initial steps toward deciphering the
      unique conformational states of cyclic octamer peptoids as supramolecular hosts
      with the aim to fully disclose their functional and dynamic properties.

PMID- 30226389
TI  - Visible-Light Photoredox-Catalyzed Hydroalkoxymethylation of Activated Alkenes
      Using alpha-Silyl Ethers as Alkoxymethyl Radical Equivalents.
AB  - A new neutral silicon-based traceless activation group (TAG) for visible-light
      photoredox-catalyzed hydroalkoxymethylation of alkenes is presented. This
      reaction involves in-situ-generated alkoxymethyl radical via single electron
      oxidation (SET) of alpha-TMS-substituted ethers, followed by subsequent conjugate
      addition to activated alkenes. Various functional groups were tolerated both
      under mild metal and metal-free conditions to provide good to excellent yields.
      Furthermore, the addition products were transformed to valuable synthetic
      building blocks, such as carboxylic acids, gamma-butyrolactones, and complex aryl
      alkyl ethers.

PMID- 30226390
TI  - Yogurt and green tea regimen in the preventions of heart disease and cancer in
      men.

PMID- 30226391
TI  - Oxidative/nitrative stress in the pathogenesis of systemic sclerosis: are
      antioxidants beneficial?
AB  - Systemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from
      the clinical side by progressive vasculopathy and fibrosis of the skin and
      different organs and from the biochemical side by fibroblast deregulation with
      excessive production of collagen and increased expression of nicotinamide adenine
      dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an
      overproduction of reactive oxygen species that through an autocrine loop
      maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are
      implicated in the origin and perpetuation of several clinical manifestations of
      SSc having vascular damage in common; attempts to dampen oxidative and nitrative
      stress through different agents with antioxidant properties have not translated
      into a sustained clinical benefit. Objective of this narrative review is to
      describe the origin and clinical implications of oxidative and nitrative stress
      in SSc, with particular focus on the central role of NOX4 and its interactions,
      to re-evaluate the antioxidant approaches so far used to limit disease
      progression, to appraise the complexity of antioxidant treatment and to touch on
      novel pathways elements of which may represent specific treatment targets in the
      not so distant future.

PMID- 30226392
TI  - Acute chemical skin injuries in the United States: a review.
AB  - The objective was to perform a thorough review of published and other available
      data to elucidate the extent of chemical skin injuries in the US. Chemical skin
      injuries differ significantly from skin lesions produced by other injury
      mechanisms, so this review was restricted to the former. Retrieval of relevant
      published data was performed in PubMed and Google. Other data were retrieved from
      the American College of Surgeons National Trauma Databank, American Burn
      Association National Burn Repository, US Department of Labor Bureau of Labor
      Statistics, websites of all 50 US States Departments of Health, and the National
      Poison Data System of the American Association of Poison Control Centers. Two
      areas of significance in disfiguring skin burn injuries and particularly of
      chemical skin injuries, psychosocial issues and the associated financial burden,
      have been briefly reviewed. Because of the paucity of published data,
      international as well as US data have been included. A brief description of an
      active flushing fluid as an alternative to potable water, Diphoterine(r)
      solution, has also been included. Chemical skin injuries generally comprise
      approximately 2-5% of all skin burns, but sometimes higher percentages have been
      reported. Data analysis shows that while there are various sources regarding the
      epidemiology of chemical skin injuries, the total annual number cannot be
      determined because there is no centralized US national reporting mechanism.
      Literature and clinical experience demonstrate the importance of chemical skin
      injuries in USA. Dermal exposures to chemicals can result in mortality and
      morbidity. Chemical skin injuries can be avoided or ameliorated and preventive
      advanced measures should be taken to reduce or ameliorate them.

PMID- 30226393
TI  - Haematological and morphological evaluation of feline whole blood units collected
      for transfusion purposes.
AB  - Objectives Despite the increasing availability of feline blood collected and
      stored for transfusion purposes, few studies have been performed on feline blood
      units. The aim of this prospective in vitro study was to evaluate haematological
      and morphological changes in feline blood cells in whole blood units between
      collection and end of storage. Methods Haematological examination (red blood
      cells [RBCs], haemoglobin, haematocrit, red cell distribution width, mean cell
      volume, mean cell haemoglobin concentration, mean cell haemoglobin, white blood
      cells [WBCs] and platelet [PLT] count) was performed on 40 non-leukoreduced
      feline whole blood units at time of collection (day[D]0) and after storage (D35).
      The blood was collected into citrate-phosphate-dextrose-adenine anticoagulant
      preservative solution using an open system in a veterinary blood bank and stored
      for 35 days at 4 +/- 2 degrees C. Twenty of these feline whole blood units were
      also analysed for blood cell morphology (normal RBCs, macrocytes, echinocytes,
      spherocytes, schistocytes, lysed RBCs, RBCs with Heinz bodies and recognisable
      WBC and PLT count). Differences between the two examination times were
      statistically analysed. Results There was a statistically significant decrease in
      WBC and PLT counts after storage at D35 ( P <0.0001 for both). The most
      significant cellular morphological change after storage was an increase in
      echinocyte count ( P = 0.0001), and lysed RBCs ( P <0.0001), and a decrease in
      normal RBCs ( P <0.0001). Recognisable WBCs - mainly lymphocytes - were present
      at the end of storage. Conclusions and relevance This study showed that
      significant morphological changes occur in RBCs in feline blood units during
      storage for 35 days. In vivo studies are required to establish if these changes
      could affect the ability of stored RBCs to circulate and provide adequate oxygen
      delivery after transfusion.

PMID- 30226394
TI  - Meta-analysis of long-term outcomes of percutaneous coronary intervention versus
      medical therapy in stable coronary artery disease.

PMID- 30226395
TI  - Integration Host Factor is Essential for Biofilm formation, Extracellular enzyme,
      Zeamine Production and Virulence in Dickeya zeae.
AB  - Dickeya zeae is a globally important pathogenic bacterium that infects a number
      of crops, including rice, maize, potato, and banana. Bacterial foot rot of rice
      caused by D. zeae is one of the most important bacterial diseases of rice in
      China and some Southeast Asian countries. To investigate the functions of
      integration host factor (IHF) in D. zeae, we generated knockout mutants of ihfA
      and ihfB. Phenotypic assays showed that both the DeltaihfA and DeltaihfB strains
      had greatly reduced mobility, biofilm formation, extracellular protease and
      pectinase activities, and toxin production compared with the wild-type strain. In
      addition, the mutants did not inhibit the germination of rice seeds, failed to
      cause soft rot in potatoes and a hypersensitive response in tobacco, and were
      avirulent in rice. Quantitative reverse-transcription polymerase chain reaction
      analysis demonstrated that IHF positively regulates the expression of zmsA,
      hrpN/Y, pelA/B/C, pehX, celZ, prtG, fliC, and DGC. Electrophoretic mobility shift
      assays further confirmed that IhfA binds to the promoter region of the
      diguanylate cyclase gene and alters the levels of a second bacterial messenger, c
      di-GMP, to regulate the pathogenicity or other physiological functions of D.
      zeae. In summary, IHF is an important integrated regulator of pathogenicity in D.
      zeae.

PMID- 30226396
TI  - A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to
      melanoma patients.
AB  - Oncolytic viruses represent a unique type of agents that combine self
      amplification, lytic and immunostimulatory properties against tumors. A local and
      locoregional clinical benefit has been demonstrated upon intratumoral injections
      of an oncolytic herpes virus in melanoma patients, leading to its approval in USA
      and Europe for patients without visceral disease (up to stage IVM1a). However, in
      order to debulk and change the local immunosuppressive environment of tumors that
      cannot be injected directly, oncolyitc viruses need to be administered
      systemically. Among different viruses, adenovirus has been extensively used in
      clinical trials but with few evidences of activity upon systemic administration.
      Preclinical efficacy of a single intravenous administration of our oncolytic
      adenovirus ICOVIR5, an adenovirus type 5 responsive to the pRB pathway commonly
      deregulated in tumors, led us to use this virus in a dose-escalation phase I
      trial in metastatic melanoma patients. The results in 12 patients, treated with a
      single infusion of a dose up to 1E13 viral particles, show that ICOVIR5 can reach
      melanoma metastases upon a single intravenous administration but fails to induce
      tumor regressions. These results support the systemic administration of armed
      oncolytic viruses to treat disseminated cancer.

PMID- 30226397
TI  - A review on the current situation and challenges of colistin resistance in
      poultry production.
AB  - Colistin has been re-assessed as a critically important antimicrobial in humans
      due to its efficacy against multi-drug resistant Gram-negative bacteria, in
      particular P. aeruginosa, A. baumannii, and K. pneumoniae. The recent discovery
      of mobile colistin resistance (mcr) determinants in humans and animals has
      brought concerns regarding the future of this antimicrobial. In this paper, we
      aim to highlight the current challenges with colistin resistant bacteria and to
      summarize reliable global data on colistin resistance in poultry production. In
      addition, we present and compare data from a screening for colistin resistance
      carried out on a collection of clinical Escherichia coli isolated from poultry in
      Italy. In Europe, resistance rates for Salmonella and E. coli are in general low
      with sporadic incidence of high colistin resistance levels. Absence of resistance
      or very low rates have been recorded in countries where colistin is either not
      employed (e.g. Norway) or used in minimal amounts (e.g. Denmark) in food
      producing animals. In large poultry meat producing countries, such as China and
      Brazil, the widespread use of colistin has resulted in the dissemination of
      resistance determinants in diverse bacterial species. Worryingly, these bacteria
      are often co-resistant to other critically important antimicrobials, such as
      extended-spectrum cephalosporins. The data gap for many countries and for
      zoonotic bacteria, the role of the "phantom resistome" and the circulation of mcr
      carriers expressing resistance phenotypes close or below the current ECOFF
      values, should be considered in future investigations. The importance of poultry
      as a cheap protein source and the global effort to mitigate colistin resistance
      and preserve this essential antimicrobial require a thorough re-assessment of
      colistin use in poultry.

PMID- 30226398
TI  - Multistimuli-responsive drug vehicles based on gold nanoflowers for
      chemophotothermal synergistic cancer therapy.
AB  - AIM: To design and synthesize a novel multistimuli-responsive drug vehicle based
      on gold nanoflowers (AuNFs) for chemophotothermal synergistic cancer therapy.
      MATERIALS & METHODS: Multistimuli-responsive drug-delivery system based on
      doxorubicin (DOX)/polydopamine (PDA)-functionalized AuNFs (Lan-AuNFs@PDA/DOX) was
      prepared. The structural characteristics, photothermal properties and stimuli
      responsive drug release properties of Lan-AuNFs@PDA/DOX were evaluated. Antitumor
      studies in vivo and in vitro were performed. RESULTS: Lan-AuNFs@PDA/DOX exhibited
      uniform morphology, excellent biocompatibility and photothermal conversion
      efficiency, which could also respond to stimulus including near infrared light
      and pH to trigger on demand drug release. The excellent synergistic therapeutic
      efficacy was confirmed both in vitro and in vivo. CONCLUSION: Lan-AuNFs@PDA/DOX
      would be a promising drug carrier, endowing a great potential for multistimuli
      responsive chemophotothermal synergistic cancer therapy.

PMID- 30226399
TI  - Residential Proximity to Major Roadways at Birth, DNA Methylation at Birth and
      Midchildhood, and Childhood Cognitive Test Scores: Project Viva(Massachusetts,
      USA).
AB  - BACKGROUND: Epigenetic variability is hypothesized as a regulatory pathway
      through which prenatal exposures may influence child development and health.
      OBJECTIVE: We sought to examine the associations of residential proximity to
      roadways at birth and epigenome-wide DNA methylation. We also assessed
      associations of differential methylation with child cognitive outcomes. METHODS:
      We estimated residential proximity to roadways at birth using a geographic
      information system (GIS) and cord blood methylation using Illumina's
      HumanMethylation450-array in 482 mother-child pairs in Project Viva. We
      identified individual CpGs associated with residential-proximity-to-roadways at
      birth using robust linear regression [[Formula: see text]]. We also estimated
      association between proximity-to-roadways at birth and methylation of the same
      sites in blood samples collected at age 7-11 y ([Formula: see text]). We ran the
      same analyses in the Generation R Study for replication ([Formula: see text]). In
      Project Viva, we investigated associations of differential methylation at birth
      with midchildhood cognition using linear regression. RESULTS: Living closer to
      major roadways at birth was associated with higher cord blood (and-more weakly
      midchildhood blood) methylation of four sites in LAMB2. For each halving of
      residential-proximity-to-major-roadways, we observed a 0.82% increase in DNA
      methylation at cg05654765 [95% confidence interval (CI): (0.54%, 1.10%)], 0.88%
      at cg14099457 [95% CI: (0.56%, 1.19%)], 0.19% at cg03732535 [95% CI: (0.11%,
      0.28)], and 1.08% at cg02954987 [95% CI: (0.65%, 1.51%)]. Higher cord blood
      methylation of these sites was associated with lower midchildhood nonverbal
      cognitive scores. Our results did not replicate in the Generation R Study.
      CONCLUSIONS: Our discovery results must be interpreted with caution, given that
      they were not replicated in a separate cohort. However, living close to major
      roadways at birth was associated with cord blood methylation of sites in LAMB2-a
      gene known to be linked to axonal development-in our U.S. cohort. Higher
      methylation of these sites associated with lower nonverbal cognitive scores at
      age 7-11 y in the same children. https://doi.org/10.1289/EHP2034.

PMID- 30226400
TI  - Disorders of Consciousness due to Traumatic Brain Injury: Functional Status Ten
      Years Post-Injury.
AB  - Few studies have assessed the long-term functional outcomes of patients with a
      disorder of consciousness due to traumatic brain injury (TBI). This study
      examined functional status during the first 10 years after TBI among a cohort
      with disorders of consciousness (i.e., coma, vegetative state, minimally
      conscious state). The study sample included 110 individuals with TBI who were
      unable to follow commands prior to inpatient rehabilitation and for whom follow
      up data were available at 1, 2, 5, and 10 years post-injury. The sample was
      subdivided into those who demonstrated command-following early (before 28 days
      post-injury) versus late (>= 28 days post-injury or never). Functional
      Independence Measure (FIM) at 1, 2, 5, and 10 years following TBI was used to
      measure functional outcomes. Measureable functional recovery occurred throughout
      the 10-year period, with more than two thirds of the sample achieving
      independence in mobility and self-care, and about one quarter achieving
      independent cognitive function by 10 years. Following commands prior to 28 days
      was associated with greater functional independence at all outcome time-points.
      Multi-trajectory modeling of recovery of three FIM subscales (self-care,
      mobility, cognition) revealed four distinct prognostic groups with different
      temporal patterns of change on these subscales. More than half the sample
      achieved near-maximal recovery by 1 year post-injury, while the later command
      following subgroups recovered over longer periods of time. Significant late
      functional decline was not observed in this cohort. Among a cohort of patients
      unable to follow commands at the time of inpatient rehabilitation, a substantial
      proportion achieved functional independence in self-care, mobility, and
      cognition. The proportion of participants achieving functional independence
      increased between 5 and 10 years post-injury. These findings suggest that
      individuals with disorders of consciousness may benefit from ongoing functional
      monitoring and updated care plans for at least the first decade after TBI.

PMID- 30226401
TI  - Phosphorus spectroscopy in acute TBI demonstrates metabolic changes that relate
      to outcome in the presence of normal structural MRI.
AB  - Metabolic dysfunction is a key pathophysiological process in the acute phase of
      traumatic brain injury (TBI). Although changes in brain glucose metabolism and
      extracellular lactate/pyruvate ratio are well known, it was hitherto unknown
      whether these translate to downstream changes in ATP metabolism and intracellular
      pH. We have performed the first clinical voxel-based in vivo phosphorus magnetic
      resonance spectroscopy (31P MRS) in 13 acute-phase major TBI patients versus 10
      healthy controls (HCs), at 3T, focusing on eight central 2.5 * 2.5 * 2.5 cm3
      voxels per subject. PCr/gammaATP ratio (a measure of energy status) in TBI
      patients was significantly higher (median = 1.09) than that of HCs (median =
      0.93) (p < 0.0001), due to changes in both PCr and ATP. There was no significant
      difference in PCr/gammaATP between TBI patients with favourable and unfavourable
      outcome. Cerebral intracellular pH of TBI patients was significantly higher
      (median = 7.04) than that of HCs (median = 7.00) (p = 0.04). Alkalosis was
      limited to patients with unfavourable outcome (median = 7.07) (p < 0.0001). These
      changes persisted after excluding voxels with > 5% radiologically visible injury.
      This is the first clinical demonstration of brain alkalosis and elevated
      PCr/gammaATP ratio acutely after major TBI. 31P MRS has potential for non
      invasively assessing brain injury in the absence of structural injury, predicting
      outcome and monitoring therapy response.

PMID- 30226402
TI  - Atypical presentation and imaging features of postpartum posterior reversible
      encephalopathy syndrome.

PMID- 30226403
TI  - Role of Nogo Receptor-1 for Recovery of Balance, Cognition, and Emotion after
      Mild Traumatic Brain Injury in Mice.
AB  - Mild traumatic brain injury (mTBI) constitutes 75 ~ 90% of all TBI cases and
      causes various physical, cognitive, emotional, and other psychological symptoms.
      Nogo receptor 1 (NgR1) is a regulator of structural brain plasticity during
      development and in adulthood. Here, we used mice that, in the absence of
      doxycycline, overexpress NgR1 in forebrain neurons (MemoFlex) to determine the
      role of NgR1 in recovery from mTBI with respect to balance, cognition, memory,
      and emotion. We compared wild-type (WT), MemoFlex, and MemoFlex + doxycycline
      mice to the same three groups subjected to mTBI. mTBI was induced by a controlled
      30-g weight drop. We found that inability to downregulate NgR1 significantly
      impairs recovery from mTBI-induced impairments. When the NgR1 transgene was
      turned off, recovery was similar to that of WT mice. The results suggest that the
      ability to regulate NgR1 signaling is needed for optimal recovery of motor
      coordination and balance, spatial memory, cognition, and emotional functions
      after mTBI.

PMID- 30226404
TI  - The potential of biomimetic nanoparticles for tumor-targeted drug delivery.
AB  - In past decades, rapid progress in nanoparticle (NP) synthesis and engineering
      has provided a broad range of nanoscale agents affording both therapeutic and
      diagnostic functions. More recently, the emergence of biomimetic NPs as an
      efficient and promising technology has further expanded this field. The
      employment of biomemetic NPs offers many distinct advantages, including enhanced
      stability, the solubilization of hydrophobic payloads, extended blood residence
      times and the ability to better target a region of interest. In this review, we
      focus on two main categories of biomimetic NPs, protein/peptide-templated
      biomimetic NPs and cell membrane-derived biomimetic NPs. The properties,
      applications and challenges of these biomimetic NPs in tumor diagnosis and
      treatment are discussed. The pros and cons, and future development, of biomimetic
      NPs are also considered.

PMID- 30226405
TI  - Semi-Rigid Ureteroscopy Should Not Be the First Option for Proximal Ureteral
      Stones in Children.
AB  - PURPOSE: To investigate the factors that predict the success and complication
      rates of semi-rigid ureteroscopy (URS) in pediatric population. MATERIALS AND
      METHODS: This is a retrospective analysis of the database including 182 patients
      who underwent URS between 2001 and 2016. The possible factors that might affect
      the outcome were age, gender, stone laterality, largest stone size, number of
      stones, stone location, orifice dilatation status, and caliber of ureteroscope.
      RESULTS: The mean age was 68.1 (7-204) months, and male-to-female ratio was
      94:88. Operative side was left for 97, right for 82, and bilateral for 3
      patients. One hundred and forty-four patients had a single stone, and 38 patients
      had multiple stones. The median largest stone size was 7 (2-20) mm. Postoperative
      ureteral stenting was performed in 150 (86.2%) patients. The overall success rate
      was 84.6%, while 81.6% and 85.4% in 8F URS and 4.5F URS groups, respectively (p =
      0.560). Stone-free rate was higher among patients who were older than 36 months,
      distal ureteral stones and single stones (p = 0.012, 0.002, and 0.009,
      respectively). Complication rate was higher for proximally located stones (p =
      0.029). The mean follow-up was 23.9 +/- 32.5 months. CONCLUSION: URS is a safe
      procedure with acceptable success rates in the pediatric population. Younger age,
      multiple stones, and proximal location are the predisposing factors for failure,
      whereas proximal location was the only factor for complication occurrence.
      Therefore, semi-rigid ureteroscopy should not be the first choice in the
      treatment of proximal ureteral stones, and alternative methods should be
      preferred, if available.

PMID- 30226406
TI  - The Causal Influence of Perceived Social Norms on Intimate Partner Violence
      Perpetration: Converging Cross-Sectional, Longitudinal, and Experimental Support
      for a Social Disinhibition Model.
AB  - Across three studies, we develop a model of the direct and indirect paths through
      which the perceived prevalence (perceived descriptive norms [PDN]) of intimate
      partner violence (IPV) among peers may influence individuals' likelihood of
      engaging in IPV. Study 1 replicated and extended previous cross-sectional
      research by demonstrating a positive longitudinal association between PDN and
      subsequent IPV perpetration. Study 2 further showed the influence of PDN on IPV
      perpetration to be mediated through its relation to perceived peer acceptance of
      IPV (perceived injunctive norms [PIN]), which in turn predicted personal IPV
      acceptance. Study 3 built on this model using an experimental paradigm to show
      that increasing PDN leads to corresponding increases in PIN and, in turn,
      personal IPV acceptance, which both predicted IPV perpetration. Furthermore, the
      effects of PIN on personal IPV acceptance and IPV propensity were strongest for
      dominance-oriented individuals. Results bear important implications for social
      norms-based interventions for IPV.

PMID- 30226407
TI  - Submaximal Marker for Investigating Peak Muscle Torque Using Neuromuscular
      Electrical Stimulation after Paralysis.
AB  - Spinal cord injury (SCI) results in deleterious skeletal muscle adaptations, such
      as relevant atrophy and loss of force. In particular, the relevant loss of lower
      limb force-generating capacity may limit functional mobility even if neuronal
      control was sufficient. Currently, methods of assessing maximal force-generating
      capacity using neuromuscular electrical stimulation (NMES) are limited in
      individuals who cannot tolerate higher stimulation amplitudes, such as those with
      residual sensation and those at risk of fracture. In this study, we examined the
      relationship between NMES amplitude and muscle torque exerted (recruitment curve)
      in order to determine whether maximal torque output can be characterized by a
      submaximal marker. Recruitment curves for knee extensors, knee flexors, and ankle
      plantarflexors were recorded from 30 individuals with motor complete SCI. NMES
      was delivered starting with an amplitude of 5 mA, and increasing by 5 mA for
      every subsequent stimulation until either the participant requested to stop the
      stimulation or the maximum stimulation amplitude (140 mA) was reached.
      Significant correlations between peak slope of the recruitment curve and peak
      torque for all muscle groups were found (knee extensors, r = 0.75; p < 0.0001;
      knee flexors, r = 0.68; p < 0.0001; ankle plantarflexors, r = 0.91; p < 0.0001),
      indicating that muscles that show greater peak slope of the recruitment curve
      tend to generate a greater peak torque. This suggests that peak slope, which was
      achieved at an average stimulation intensity (55.0 mA) that was 43% smaller than
      that corresponding to peak torque (97.4 mA), may be used as a submaximal marker
      for characterizing maximal torque output in individuals with SCI.

PMID- 30226408
TI  - Congenital glioblastoma multiforme presented with intracranial bleeding: a case
      report.

PMID- 30226409
TI  - The Surgical Experience Influences the Safety and Efficacy of Photovaporization
      of Prostate with 180-W XPS GreenLight Laser: Comparison Between Novices vs Expert
      Surgeons Learning Curves.
AB  - PURPOSE: To assess the extent to which surgical experience can affect
      perioperative and functional outcomes after photoselective vaporization of the
      prostate (PVP) with 180W XPX GreenLight laser in patients with lower urinary
      tract symptoms secondary to benign prostatic obstruction (BPO). MATERIALS AND
      METHODS: Data from 291 consecutive patients with symptomatic BPO (median follow
      up 12 m) were collected and analyzed. Patients were treated at 2 different
      institutions by 2 expert (G1, n = 182) and 2 novice (G2, n = 109) transurethral
      prostate surgeons (February 2013 - March 2017) and underwent standard or
      anatomical PVP depending on surgeons' preferences. Patients' characteristics,
      perioperative and functional outcomes were compared using the chi-square and Mann
      Whitney U tests. Patients' satisfaction was measured using the Patient Global
      Impression of Improvement (PGI-I) score. Learning curves were analyzed based on
      changes in quantitative parameters: surgery time, lasing/operative time, and
      energy delivered (kJ). RESULTS: Patients' baseline characteristics, perioperative
      data and PGI-I score were similar. Overall the complication rates showed better
      trends for G1. Serum prostate-specific antigen levels, maximum flow rate, and
      International Prostatic Symptoms Score improved in both groups, with perceived
      improvements greater in G2 (p < 0.006). Lasing time/operative time ratio showed
      greater evolution for G1 than G2 (0.50:IQR 0.38-0.60 vs 0.46:IQR 0.34-0.58,
      respectively)(p = 0.201). A major increase in energy delivery for G2 was achieved
      within the first 50 procedures, whereas more than 100 iterations were needed for
      G1 to reach LT/OT >60%. CONCLUSION: Surgeons' background and expertise appear to
      affect outcomes over the learning curve, with roughly similar perioperative and
      functional results.

PMID- 30226410
TI  - Working memory and behavioral inhibition in children with attention
      deficit/hyperactivity disorder (ADHD): an examination of varied central executive
      demands, construct overlap, and task impurity.
AB  - The stop-signal paradigm is the premier metric of behavioral inhibition in
      contemporary attention-deficit/hyperactivity disorder (ADHD) research. The stop
      signal paradigm's choice-reaction time component, however, arguably places
      greater demands on working memory processes (e.g., controlled-focused attention)
      relative to alternative inhibition metrics (i.e., go/no-go (GNG) tasks), and
      consequently obscures conclusions about inhibition and working memory deficits in
      affected children. The current study, therefore, aimed to determine whether
      shared variance between stop-signal behavioral inhibition and working memory
      performance in children with ADHD reflects overlap between the working memory and
      inhibition constructs or insufficient specificity of the stop-signal paradigm.
      Fifty-five children (8-12 years) with and without ADHD were administered
      established phonological (PH) and visuospatial (VS) working memory measures, as
      well as stop-signal and GNG tasks that vary with respect to demands on controlled
      focused attention. Although working memory and GNG performance each uniquely
      predicted children's inattention, stop-signal task performance was not a
      significant predictor of unique variance in inattention, above and beyond
      variance associated with working memory. Collectively, these findings suggest
      that performance on the stop-signal task, compared to the GNG task, is confounded
      by greater demands associated with working memory and consequently reflects an
      impure estimate of the inhibition construct.

PMID- 30226411
TI  - Routines and Meaning in Life.
AB  - Previous research links the experience of meaning in life (MIL) with
      environmental structure and the coherence of external stimuli. The current
      studies directly test the association between one source of structure in everyday
      life-routines-and MIL. First, Study 1 ( N = 317) found a positive relationship
      between trait preference for routine and MIL. Study 2 expanded upon this cross
      sectional finding with experience sampling data ( N = 85; 2,590 episodes) showing
      that the degree to which current, naturally occurring, behavior followed a
      typical routine positively related to participants' momentary feelings of MIL.
      These findings have implications for conceptualizations of MIL, suggesting a
      previously unnoted, mundane, and ubiquitous source of MIL. The potential roles of
      boredom and novelty and individual and situational differences for these effects
      are discussed.

PMID- 30226412
TI  - Cardiovascular and Self-Regulatory Consequences of SES-Based Social Identity
      Threat.
AB  - This work examined the effects of socioeconomic status (SES)-based social
      identity threat on cardiovascular indexes of challenge and threat and self
      regulatory strength. Participants ( N = 104) took an exam described as either
      diagnostic of intellectual ability (identity threat) or framed as a problem
      solving task (control) while we recorded cardiovascular reactivity and assessed
      participants' physical self-control. Under identity threat, lower SES students
      exhibited impaired performance, reduced self-control, and cardiovascular threat
      reactivity. In contrast, higher SES students under threat exhibited the reverse
      pattern-a boost in performance, no change in self-regulation, and cardiovascular
      challenge reactivity. Furthermore, while measures of general arousal (heart rate
      and pre-ejection period) were unrelated to performance, cardiovascular patterns
      of challenge and threat were significantly associated with performance under
      identity threat. Results provide evidence that SES-based stigma influences
      physiological and self-regulatory processes.

PMID- 30226414
TI  - And In The End.

PMID- 30226413
TI  - AGuIX(r) from bench to bedside-Transfer of an ultrasmall theranostic gadolinium
      based nanoparticle to clinical medicine.
AB  - AGuIX(r) are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium
      chelates. This nanoparticle has been recently accepted in clinical trials in
      association with radiotherapy. This review will summarize the principal
      preclinical results that have led to first in man administration. No evidence of
      toxicity has been observed during regulatory toxicity tests on two animal species
      (rodents and monkeys). Biodistributions on different animal models have shown
      passive uptake in tumours due to enhanced permeability and retention effect
      combined with renal elimination of the nanoparticles after intravenous
      administration. High radiosensitizing effect has been observed with different
      types of irradiations in vitro and in vivo on a large number of cancer types
      (brain, lung, melanoma, head and neck...). The review concludes with the second
      generation of AGuIX nanoparticles and the first preliminary results on human.

PMID- 30226415
TI  - Small Toes, Huge Problems: Dealing With Lesser Toe Deformities.

PMID- 30226417
TI  - First Report of Damping-Off Caused by Pythium arrhenomanes on Rice in China.

PMID- 30226418
TI  - The Relative Occurrence of Grapevine leafroll-associated virus 3 and Grapevine
      red blotch virus in Washington State Vineyards.
AB  - Vineyard surveys were conducted for three consecutive seasons in eastern
      Washington State, the major grapevine-growing region in the state, to document
      the occurrence of Grapevine leafroll-associated virus 3 (GLRaV-3) and Grapevine
      red blotch virus (GRBV). The majority of samples were collected from red-berried
      wine grape (Vitis vinifera) cultivars exhibiting symptoms of or suspected for
      grapevine leafroll (GLD) and red blotch (GRBD) diseases. A limited number of
      samples from white-berried cultivars were collected randomly due to the lack of
      visual symptoms. Samples were collected from a total of 2,063 grapevines from 18
      red-berried cultivars and seven white-berried cultivars planted in eight American
      Viticultural Areas and tested for GLRaV-3 and GRBV using RT-PCR and PCR,
      respectively. The results showed 67.77% and 6.01% of total samples positive for
      GLRaV-3 and GRBV, respectively, and 9.06% of samples positive for both viruses.
      About 17% of samples tested negative for the two viruses, but some of these
      samples were positive for GLRaV-2 and GLRaV-4. Overall results indicated that
      GLRaV-3 was more common than GRBV, independent of cultivars and the geographic
      origin of samples. Due to variability in symptoms in red-berried cultivars, virus
      specific diagnostic assays were deemed necessary for reliable identification of
      GLRaV-3 and GRBV and to differentiate GLD and GRBD symptoms from those induced by
      biotic and abiotic stresses in vineyards. A multiplex PCR protocol was developed
      for simultaneous detection of GLRaV-3 and GRBV in grapevine samples. A global
      phylogenetic analysis of GRBV genome sequences revealed segregation of virus
      isolates from Washington State vineyards into two distinct clades, with the
      majority of isolates belonging to clade II.

PMID- 30226419
TI  - The Effect of Cold Stress on Damping-Off of Soybean Caused by Pythium sylvaticum.
AB  - To improve our understanding of the timing of cold stress and its effect on
      Pythium damping-off, we performed a factorial experiment with two cold stress
      temperatures (4 and 10 degrees C); exposure to 96 h of cold stress at 0, 1, 2, 4,
      6, and 8 days after planting; and inoculation with Pythium sylvaticum-infested
      millet or control. Increased susceptibility to damping-off resulting in reduced
      emergence was found in inoculated plants when the cold stress period began 2 or 4
      days after planting. In the noninoculated controls, no effect of cold stress on
      emergence was observed. Slower seedling growth was observed during the cold
      stress period and in inoculated plants after exposure to cold stress. Seed
      exudation, mycelial growth, and sporangia germination of P. sylvaticum was
      evaluated at 4, 10, and 18 degrees C. The greatest seed exudation was observed at
      4 degrees C. Low temperatures delayed mycelial growth of P. sylvaticum, although
      the pathogen was still able to grow at 4 degrees C. Sporangia incubated for 3 h
      at 18 degrees C in the presence of seed exudates had higher germination in
      comparison with sporangia incubated at 10 or 4 degrees C. Moreover, more
      sporangia germinated in response to seed exudates that were previously collected
      from seed imbibed for 24 h at low temperatures (4 degrees C). These results
      suggest that cold stress 2 to 4 days after planting increases soybean
      susceptibility to damping-off, presumably because of increased seed exudation and
      delayed seedling growth.

PMID- 30226420
TI  - The Distribution and Detection of Grapevine red blotch virus in its Host Depend
      on Time of Sampling and Tissue Type.
AB  - Grapevine red blotch virus (GRBV) is the causal agent of grapevine red blotch, an
      emerging disease that affects cultivated grapevine such as Vitis vinifera. The
      ability to detect viruses in grapevine is often hindered by low virus titers
      compounded by a variable distribution in the plant and seasonal variations. In
      order to examine these two variables in relation to GRBV, we developed a
      quantitative polymerase chain reaction (qPCR) method that incorporates both
      internal and external references to enhance assay robustness. In greenhouse-grown
      vines infected with GRBV, qPCR identified highest virus titers in the petioles of
      fully expanded leaves and significantly reduced levels of virus in the shoot
      extremities. In vineyard-grown vines infected with GRBV, the virus titer in July
      and October 2016 followed a pattern similar to that found for the greenhouse
      grown plants but, most strikingly, close to half (44%) of the samples analyzed in
      June 2015 tested negative for infection. The technique presented and results
      obtained highlight the variability of virus distribution in its host and provide
      a useful guide for selecting the best tissues for optimal GRBV diagnosis.

PMID- 30226421
TI  - Influence of Irrigation and Wetting Agent on Fungicide Residues in Creeping
      Bentgrass.
AB  - Fungicides (azoxystrobin, propiconazole, pyraclostrobin, and thiophanate-methyl)
      were applied to field plots of creeping bentgrass established on a sand-based
      root zone substrate and maintained at a cutting height of 0.34 cm. The wetting
      agent, a modified alkylated polyol, was applied 24 h prior to fungicide
      application. Irrigation (0.51 cm) was applied to plots immediately after the
      fungicide spray. Turf was sampled nine times over 42 days to examine fungicide
      residues in three components of the turf profile: verdure/thatch, roots, and
      soil. Residues were extracted from samples and then quantified using a liquid
      chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) procedure. The
      experiment was run twice. Wetting agent had little or no effect on fungicide
      distribution in any of the turf components. Postapplication irrigation had little
      effect on residues observed in the verdure/thatch component. Significant
      irrigation treatment effects were observed in root and soil components, but
      results varied among fungicides and sampling dates. Where significant effects
      were observed for the irrigation plus wetting agent treatment, results generally
      mirrored outcomes for irrigation treatment.

PMID- 30226422
TI  - MLST reveals a separate and novel clonal group for Acidovorax avenae strains
      causing red stripe in sugarcane from Argentina.
AB  - Acidovorax species cause a wide range of economically important diseases in
      monocotyledonous and dicotyledonous plants, including sugarcane, corn, rice,
      oats, millet, foxtail watermelon and orchids. In Argentina, the red stripe
      disease of sugarcane caused by A. avenae affects 30% of the milling stems with
      important economic losses. To explore the genetic diversity of this bacterium
      associated with red stripe in Argentina, MLST was applied. This study included 15
      local strains isolated from four different sugarcane planting regions and
      selected after RAPD analysis and reference strains of A. citrulli, A. avenae, and
      A. oryzae to investigate their phylogenetic relationships. MLST analysis resulted
      in five sequence types (STs) among the sugarcane A. avenae strains which
      constitute a clonal complex, meaning a common and close origin. Sugarcane strains
      were related to A. avenae from other hosts and distant to A. citrulli. Signals of
      frequent recombination in several lineages of A. avenae was detected and we
      observed that A. oryzae is closely related to A. avenae strains. This study
      provides valuable data in the field of epidemiological and evolutionary
      investigations of novel clone of A. avenae strains causing sugarcane red stripe.
      The knowledge of the genetic diversity and the specificity strain-host are
      important to select the genotypes with the best response to the red stripe
      disease.

PMID- 30226423
TI  - Molecular characterization and detection of 16SrIII group phytoplasma associated
      with Huanglongbing symptoms.
AB  - When Huanglongbing (HLB) was found in Brazil in 2004, 'Candidatus Liberibacter
      americanus' (Lam) was infecting most of the trees while 'Ca. L. asiaticus' (Las)
      was present in minor proportion. Currently, 'Ca. L. asiaticus' is the predominant
      bacterium associated with HLB in citrus trees in Sao Paulo (SP) and Minas Gerais
      (MG) States, the major citrus growing regions in Brazil. A phytoplasma from 16Sr
      group IX was associated with HLB symptoms in Brazil in 2007, in plants free of
      Liberibacter. In this report, HLB-samples testing negative for Las, Lam and
      16SrIX phytoplasma, were infected with 16SrIII phytoplasmas. Co-infection with
      Las and 16SrIII was also found. The 16S rRNA gene sequences from 22 samples were
      obtained and sequenced, confirming that 16Sr group III phytoplasma is associated
      with HLB symptoms in SP and MG States. Ten single nucleotide polymorphisms (SNPs)
      were found in the 1,427 bp 16SrDNA sequences from 16SrIII phytoplasmas from
      citrus, while none was detected in 16SrDNA sequences among 16SrIX phytoplasma
      from citrus. Ribosomal protein (rp) rpsSrplVrpsC gene sequences were amplified
      with 16SrIII group specific primers and sequenced from a subset of nine samples
      and assembled into three groups based on eight SNPs. SNPs in 16S rRNA and rp gene
      sequences are common in 16SrIII phytoplasmas from other hosts and this
      phytoplasma group is widespread in South America. 16SrIII phytoplasmas highly
      related are commonly found in Melia azedarach, a widespread tree in Brazil and
      Argentina. The finding of a new phytoplasma associated with HLB symptoms,
      belonging to the 16SrIII group reinforces the need to develop diagnostic tools to
      assess HLB associated microbiome.

PMID- 30226424
TI  - Genetic diversity of Pseudomonas syringae pv. actinidiae strains from different
      geographic regions in China.
AB  - Pseudomonas syringae pv. actinidiae (Psa) causes kiwifruit bacterial canker
      (KBC), with a severe infection of the kiwifruit plant resulting in heavy economic
      losses. Little is known regarding the biodiversity and genetic variation of
      populations of Psa in China. A collection of 269 strains of Psa were identified
      from 300 isolates obtained from eight sampling sites in five provinces in China.
      The profiles of 50 strains of Psa and one strain of P. syringae pv.
      actinidifoliorum (Psaf) were characterized by Rep-, IS50-P, and RAPD-PCR.
      Discriminant analysis of principal coordinates (DAPC), principal component
      analysis (PCA), and hierarchical cluster analysis were used to analyze the
      combined fingerprints of the different PCR assays. The results revealed that all
      isolates belonged to the Psa3 group, that strains of Psa from China have broad
      genetic variability that was related to source geographic region, and that
      Chinese strains can be readily differentiated from strains from France, but are
      very similar to those from Italy. Multilocus sequence typing (MLST) of 24
      representative isolates using the concatenated sequences of five housekeeping
      genes (cts, gapA, gyrB, pfk, and rpoD) demonstrated that strain Jzhy2 from China
      formed an independent clade compared to the other biovars, which possessed the
      hopH1 effector gene, but lacked the hopA1 effector gene. A constellation analysis
      based on the presence or absence of the four loci coding for phytotoxins and a
      cluster analysis based on the eleven effector genes showed that strains from
      China formed two distinct clades. All of the strains, including K3 isolated in
      1997 from Jeju, Korea, lacked the cfl gene coding for coronatine. In contrast,
      the tox-argK gene cluster coding for phaseolotoxin was detected in K3 and in the
      Biovar1 strains (K3, Kw30, and Psa92), and produced a false positive amplicon for
      the hopAM1-like gene in this study. To date, only one biovar (Biovar3) is
      represented by the strains of Psa from China, despite China being the center of
      origin for the kiwifruit.

PMID- 30226425
TI  - Working memory for self-initiated and provided spatial configurations.
AB  - During a typical day, people temporarily memorise information provided to them.
      However, they memorise as often information they actively choose themselves.
      Although prevalent in everyday behaviour, this aspect of working memory (WM), we
      term self-initiated WM, has been largely unexplored. In this study, we used a
      modified spatial span task in which participants constructed the spatial
      sequences they maintained in memory. The results of three experiments
      demonstrated that participants planned and constructed structured spatial
      sequences by minimising the distances between successive locations and by
      selecting sequences with fewer path crossings. The sequences were initiated most
      often on the top left side. Memory accuracy was enhanced when participants
      memorised self-initiated spatial sequences, even when the self-initiated and
      provided sequences were matched for structure. When asked to construct spatial
      sequences for a hypothetical competitor in a memory contest, participants
      constructed complex sequences with longer paths and more path crossings,
      suggesting that these sequence parameters were under their control. The tendency
      to initiate the spatial sequences on the top left side remained. Overall, the
      results suggest that self-initiated WM can benefit from explicit metacognitive
      knowledge of the ideal structure of memory representations and also demonstrate
      that self-initiation benefits memory beyond structure.

PMID- 30226426
TI  - The influence of social network size on speech perception.
AB  - Infants and adults learn new phonological varieties better when exposed to
      multiple rather than a single speaker. This article tests whether having a larger
      social network similarly facilitates phonological performance. Experiment 1 shows
      that people with larger social networks are better at vowel perception in noise,
      indicating that the benefit of laboratory exposure to multiple speakers extends
      to real life experience and to adults tested in their native language.
      Furthermore, the experiment shows that this association is not due to differences
      in amount of input or to cognitive differences between people with different
      social network sizes. Follow-up computational simulations reveal that the benefit
      of larger social networks is mostly due to increased input variability.
      Additionally, the simulations show that the boost that larger social networks
      provide is independent of the amount of input received but is larger if the
      population is more heterogeneous. Finally, a comparison of "adult" and "child"
      simulations reconciles previous conflicting findings by suggesting that input
      variability along the relevant dimension might be less useful at the earliest
      stages of learning. Together, this article shows when and how the size of our
      social network influences our speech perception. It thus shows how aspects of our
      lifestyle can influence our linguistic performance.

PMID- 30226427
TI  - Reaching and grasping with the tongue: Shared motor planning between hand actions
      and articulatory gestures.
AB  - Research has shown connections between articulatory mouth actions and manual
      actions. This study investigates whether forward-backward hand movements could be
      associated with vowel production processes that programme tongue
      fronting/backing, lip rounding/spreading (Experiment 1), and/or consonant
      production processes that programme tongue tip and tongue dorsum actions
      (Experiment 2). The participants had to perform either forward or backward hand
      movement and simultaneously pronounce different vowels or consonants. The results
      revealed a response benefit, measured in vocal and manual reaction times, when
      the responses consisted of front vowels and forward hand movements. Conversely,
      back vowels were associated with backward hand movements. Articulation of rounded
      versus unrounded vowels or coronal versus dorsal consonants did not produce the
      effect. In contrast, when the manual responses of forward-backward hand movements
      were replaced by precision and power grip responses, the coronal consonants [t]
      and [r] were associated with the precision grip, whereas the dorsal consonant [k]
      was associated with the power grip. We propose that the movements of the tongue
      body, operating mainly for vowel production, share the directional action
      planning processes with the hand movements. Conversely, the tongue articulators
      related to tongue tip and dorsum movements, operating mainly for consonant
      production, share the action planning processes with the precision and power
      grip, respectively.

PMID- 30226428
TI  - Introspection during short-term memory scanning.
AB  - The literature in metacognition has argued for many years that introspective
      access to our own mental content is restricted to the cognitive states associated
      with the response to a task, such as the level of confidence in a decision or the
      estimation of the response time; however, the cognitive processes that underlie
      such states were deemed inaccessible to participants' consciousness. Here, we ask
      whether participants could introspectively distinguish the cognitive processes
      that underlie two short-term memory tasks. For this purpose, we asked
      participants, on a trial-by-trial basis, to report the number of items that they
      mentally scanned during their short-term memory retrieval, which we have named
      "subjective number of scanned items." The subjective number of scanned items
      index was evaluated, in Experiment 1, immediately after a judgment of recency
      task and, in Experiment 2, after an item recognition task. Finally, in Experiment
      3, both tasks were randomly mixed. The results showed that participants'
      introspection successfully accessed the complexity of the decisional processes.

PMID- 30226429
TI  - Why do I think and talk about it? Perceived functions and phenomenology of
      episodic counterfactual thinking compared with remembering and future thinking.
AB  - People revisit situations from their past and imagine what could have happened
      had the situation played out differently. This form of hypothetical thinking is
      known as episodic counterfactual thinking. The reasons why people engage in
      episodic counterfactual thinking have not been examined in the same context with
      remembering the past and imagining the future. We addressed this gap, by focusing
      on the perceived functions and phenomenological characteristics of the most
      important episodic counterfactuals compared with episodic memories and future
      projections in younger adults. We base our analyses on four categories of
      functions previously identified for past events: reflective, social, generative,
      and ruminative. The reflective and social functions dominated across all events,
      with the reflective function being most pronounced for future projections,
      potentially suggesting a close connection between future projections and self
      regulation and/or identity formation. Counter to predictions, the ruminative
      function was not rated higher for episodic counterfactuals than for other events;
      however, ratings of ruminative function showed unique correlations with the
      emotional intensity and involuntary remembering for episodic counterfactuals.
      Overall, these results suggest that episodic counterfactuals are used for self
      reflection and social sharing more than they are used for rumination and
      generative concerns.

PMID- 30226430
TI  - The influence of short-term language-switching training on the plasticity of the
      cognitive control mechanism in bilingual word production.
AB  - This study examined the effect of short-term language-switching training on the
      cognitive control mechanism in bilingual word production. In two experiments, two
      groups of relatively proficient but unbalanced Chinese-English bilinguals
      performed a cued picture-naming task, in which they switched between their two
      languages. On two consecutive days, the participants took part in four sessions.
      The same procedure was employed on 2 days in Experiment 1, whereas the cue
      language mapping was reversed on Day 2 in Experiment 2. In both experiments,
      picture naming in the dominant language (L1, Chinese) was slower than that in the
      weaker second language (L2, English) in all sessions. In addition, the reversed
      language dominance effect was enhanced with training, suggesting that training
      proactively increases the amount of inhibition of the dominant L1 at the global
      level. Furthermore, switching costs in the L1 were reduced with training in
      Experiment 1, but not in Experiment 2. These results indicate that language
      switching training improves the efficiency of reactively exerting inhibitory
      control over the dominant L1 at the local level. However, when a cue matches with
      different target languages, the effect of training is absent at the local level.
      These findings reveal the plasticity and complexity of the cognitive control
      mechanism as a function of bilingual experience, particularly in language
      switching.

PMID- 30226431
TI  - Effect of perceived length on numerosity estimation: Evidence from the Muller
      Lyer illusion.
AB  - Previous studies showed that the magnitude information conveyed by sensory cues,
      such as length or surface, influences the ability to compare the numerosity of
      sets of objects. However, the perceptual nature of this representation and how it
      interacts with the processes involved in numerical judgements remain unclear.
      This study aims to address these issues by studying the interference of length on
      numerosity under different perceptual and response conditions. The first
      experiment shows that the influence of length does not depend on the actual
      length but on subjective values reflecting the way length is perceived in a given
      visual context. The Muller-Lyer illusion was used to manipulate the perceived
      length of two dot arrays independently of their actual length. When the length of
      two dot arrays was equal but perceived as different due to the illusion,
      participants erroneously reported differences in the number of dots contained in
      each array, evidencing a similar effect of Muller-Lyer illusion on length and
      numerosity comparison. This finding was replicated in a second experiment where
      participants had to give a verbal estimate of the number of dots contained in a
      given array, thereby eliminating the choice between a small or large response.
      Compared with a neutral condition, estimations were systematically larger than
      the actual number of dots as the illusory length increased. These results
      demonstrate that the illusory-induced experience of length influences numerosity
      estimation over and beyond objective cues and that this influence is not a
      response selection bias.

PMID- 30226432
TI  - Investigating gaze processing in euthymic bipolar disorder: Impaired ability to
      infer mental state and intention, but preservation of social attentional
      orienting.
AB  - Euthymic bipolar disorder (BD) has been associated with subtle impairment in face
      processing. However, it is not known whether their difficulties extend to the
      processing of gaze. In the present study, two tasks, both of which rely on the
      ability to make use of the eye region of a pictured face, were used: the Reading
      the Mind in the Eyes test and the Eye-gaze cueing task. Compared to healthy
      controls, BD patients were impaired at judging mental state from images of the
      face but showed normal susceptibility to the direction of gaze as an attentional
      cue. These findings suggest that BD patients present selective gaze processing
      impairment, limited to the sensitivity to intention and emotion. This impairment
      could account at least partially for the higher levels of interpersonal problems
      generally observed in BD.

PMID- 30226433
TI  - An item-level analysis of lexical-semantic effects in free recall and recognition
      memory using the megastudy approach.
AB  - Psycholinguists have developed a number of measures to tap different aspects of a
      word's semantic representation. The influence of these measures on lexical
      processing has collectively been described as semantic richness effects. However,
      the effects of these word properties on memory are currently not well understood.
      This study examines the relative contributions of lexical and semantic variables
      in free recall and recognition memory at the item-level, using a megastudy
      approach. Hierarchical regression of recall and recognition performance on a
      number of lexical-semantic variables showed task-general effects where the
      structural component, frequency, number of senses, and arousal accounted for
      unique variance in both free recall and recognition memory. Task-specific effects
      included number of features, imageability, and body-object interaction, which
      accounted for unique variance in recall, whereas age of acquisition, familiarity,
      and extremity of valence accounted for unique variance in recognition. Forward
      selection regression analyses generally converged on these findings. Hierarchical
      regression also revealed that lexical variables accounted for more variance in
      recognition compared with recall, whereas semantic variables accounted for more
      unique variance above and beyond lexical variables in recall compared with
      recognition. Implications of the findings are discussed.

PMID- 30226434
TI  - The role of speech fidelity in the irrelevant sound effect: Insights from noise
      vocoded speech backgrounds.
AB  - The Irrelevant Sound Effect (ISE) is the finding that background sound impairs
      accuracy for visually presented serial recall tasks. Among various auditory
      backgrounds, speech typically acts as the strongest distractor. Based on the
      changing-state hypothesis, speech is a disruptive background because it is more
      complex than other nonspeech backgrounds. In the current study, we evaluate an
      alternative explanation by examining whether the speech-likeness of the
      background (speech fidelity) contributes, beyond signal complexity, to the ISE.
      We did this by using noise-vocoded speech as a background. In Experiment 1, we
      varied the complexity of the background by manipulating the number of vocoding
      channels. Results indicate that the ISE increases with the number of channels,
      suggesting that more complex signals produce greater ISEs. In Experiment 2, we
      varied complexity and speech fidelity independently. At each channel level, we
      selectively reversed a subset of channels to design a low-fidelity signal that
      was equated in overall complexity. Experiment 2 results indicated that speech
      like noise-vocoded speech produces a larger ISE than selectively reversed noise
      vocoded speech. Finally, in Experiment 3, we evaluated the locus of the speech
      fidelity effect by assessing the distraction produced by these stimuli in a
      missing-item task. In this task, even though noise-vocoded speech disrupted task
      performance relative to silence, neither its complexity nor speech fidelity
      contributed to this effect. Together, these findings indicate a clear role for
      speech fidelity of the background beyond its changing-state quality and its
      attention capture potential.

PMID- 30226435
TI  - Metacognitive judgements of perceptual-motor steering performance.
AB  - Control of skilled actions requires rapid information sampling and processing,
      which may largely be carried out subconsciously. However, individuals often need
      to make conscious strategic decisions that ideally would be based upon accurate
      knowledge of performance. Here, we determined the extent to which individuals
      have explicit awareness of their steering performance (conceptualised as
      "metacognition"). Participants steered in a virtual environment along a bending
      road while attempting to keep within a central demarcated target zone. Task
      demands were altered by manipulating locomotor speed (fast/slow) and the target
      zone (narrow/wide). All participants received continuous visual feedback about
      position in zone, and one sub-group was given additional auditory warnings when
      exiting/entering the zone. At the end of each trial, participants made a
      metacognitive evaluation: the proportion of the trial they believed was spent in
      the zone. Overall, although evaluations broadly shifted in line with task
      demands, participants showed limited calibration to performance. Regression
      analysis showed that evaluations were influenced by two components: (a) direct
      monitoring of performance and (b) indirect task heuristics estimating performance
      based on salient cues (e.g., speed). Evaluations often weighted indirect task
      heuristics inappropriately, but the additional auditory feedback improved
      evaluations seemingly by reducing this weighting. These results have important
      implications for all motor tasks where conscious cognitive control can be used to
      influence action selection.

PMID- 30226436
TI  - The role of contextual information during skilled anticipation.
AB  - In dynamic, temporally constrained tasks, individuals often need to anticipate
      what will happen next prior to information becoming available within the
      environment. In such situations, the availability of contextual information can
      facilitate anticipation, often in conjunction with postural information. While
      many researchers have identified the specific sources of postural information
      facilitating anticipation, few have investigated the specific sources of
      contextual information employed. In two experiments, we presented skilled and
      less-skilled tennis players with animations of rallies from real matches that
      omitted access to postural information from the opponent, constraining
      participants to anticipate based on contextual information alone. In Experiment
      1, participants anticipated the outcome of an opponent's shot under three
      conditions in which the sequence length (i.e., number of shots in a rally)
      preceding the same occluded shot was varied. Participants anticipated shot
      direction more accurately when the preceding shot sequence was presented than
      not. In Experiment 2, we presented animations that depicted the ball, the
      players, or both, in either dynamic or still form. Those conditions in which only
      the ball was depicted yielded the lowest response accuracy scores. It appears
      that information from the player and ball motion is required to provide the
      context under which skilled performers can consciously pick up and utilise
      information to anticipate more accurately than their less-skilled counterparts.

PMID- 30226437
TI  - Lift speed moderates the effects of muscle activity on perceived heaviness.
AB  - Research has shown that perceived heaviness is a function of the ratio of muscle
      activity (measured by electromyogram [EMG]) to the resulting acceleration of the
      object. However, objects will commonly be lifted at different speeds, implying
      variation in both EMG and acceleration. This study examined the effects of
      lifting speed by having participants report perceived heaviness for objects
      lifted by elbow flexion at three different speeds: slow, preferred, and fast. EMG
      and angular acceleration were recorded during these lifts. Both EMG and angular
      acceleration changed across lift speed. Nevertheless, despite these variations,
      perceived heaviness consistently scaled to the ratio of EMG to angular
      acceleration. The exponents on these parameters suggested that the saliency of
      muscle activity and movement changed across the three lift speeds.

PMID- 30226438
TI  - Gaze in a real-world social interaction: A dual eye-tracking study.
AB  - People communicate using verbal and non-verbal cues, including gaze cues. Gaze
      allocation can be influenced by social factors; however, most research on gaze
      cueing has not considered these factors. The presence of social roles was
      manipulated in a natural, everyday collaborative task while eye movements were
      measured. In pairs, participants worked together to make a cake. Half of the
      pairs were given roles ("Chef" or "Gatherer") and the other half were not. Across
      all participants we found, contrary to the results of static-image experiments,
      that participants spent very little time looking at each other, challenging the
      generalisability of the conclusions from lab-based paradigms. However,
      participants were more likely than not to look at their partner when receiving an
      instruction, highlighting the typical coordination of gaze cues and verbal
      communication in natural interactions. The mean duration of instances in which
      the partners looked at each other (partner gaze) was longer in the roles
      condition, and these participants were quicker to align their gaze with their
      partners (shared gaze). In addition, we found some indication that when hearing
      spoken instructions, listeners in the roles condition looked at the speaker more
      than listeners in the no roles condition. We conclude that social context can
      affect our gaze behaviour during a social interaction.

PMID- 30226439
TI  - Foggy windows: Pupillary responses during task preparation.
AB  - We investigated pupil dilation in 96 subjects during task preparation and during
      a post-trial interval in a visual search task and an auditory working memory
      task. Completely informative difficulty cues (easy, medium, or hard) were
      presented right before task preparation to examine whether pupil dilation
      indicated advance mobilisation of attentional resources; functional magnetic
      resonance imaging (fMRI) studies have argued for the existence of such task
      preparation, and the literature shows that pupil dilation tracks attentional
      effort during task performance. We found, however, little evidence for such task
      preparation. In the working memory task, pupil size was identical across cues,
      and although pupil dilation in the visual search task tracked the cue, pupil
      dilation predicted subsequent performance in neither task. Pupil dilation
      patterns in the post-trial interval were more consistent with an effect of
      emotional reactivity. Our findings suggest that the mobilisation of attentional
      resources in the service of the task does not occur during the preparatory
      interval, but is delayed until the task itself is initiated.

PMID- 30226440
TI  - c-Myc Is a Major Determinant for Antitumor Activity of Aurora A Kinase Inhibitor
      MLN8237 in Thyroid Cancer.
AB  - BACKGROUND: c-Myc is overexpressed in different types of cancer, including
      thyroid cancer, and has been considered undruggable. There is evidence showing
      that MLN8237, a type of aurora A kinase (AURKA) inhibitor, destabilizes c-Myc
      proteins in liver cancer cells through disruption of the c-Myc/AURKA complex.
      However, the role of MLN8237 in thyroid cancer remains largely unclear. The aims
      of this study were to test the therapeutic potential of MLN8237 in thyroid
      cancer, and to analyze determinant factors affecting the response of thyroid
      cancer cells to MLN8237 and clarify the corresponding mechanism. METHODS: The
      phenotypic effects of MLN8237 in thyroid cancer cells were evaluated through a
      series of in vitro and in vivo experiments, and the mechanism of c-Myc affecting
      MLN8237 response were explored using Western blot, ubiquitination, and
      cycloheximide chase assays. RESULTS: The data show that the levels of c-Myc
      protein were strongly associated with MLN8237 cellular response in thyroid cancer
      cells. Only the cells with high c-Myc expression exhibited growth inhibition upon
      MLN8237 treatment. However, MLN8237 barely affected the growth of those with low
      c-Myc expression. Mechanistically, MLN8237 dramatically promoted proteasomal
      degradation of c-Myc proteins through disruption of the c-Myc/AURKA complex in
      the cells with high c-Myc expression. A similar antitumor activity of MLN8237 was
      also found in xenograft tumor models. CONCLUSIONS: The data demonstrate that c
      Myc is a major determinant for MLN8237 responsiveness in thyroid cancer cells.
      Thus, indirectly targeting c-Myc by MLN8237 may be an effective strategy for
      thyroid cancer overexpressing c-Myc.

PMID- 30226441
TI  - Initial Ablation Ratio: Quantitative Value Predicting the Therapeutic Success of
      Thyroid Radiofrequency Ablation.
AB  - BACKGROUND: The aims of this study were to determine a quantitative index, the
      initial ablation ratio (IAR), representing the amount of ablation, to predict
      therapeutic success and to evaluate the correlation between the IAR and volume
      reduction ratio (VRR). METHODS: Among the patients who underwent radiofrequency
      ablation (RFA) for the treatment of benign thyroid nodules at the Withsim Clinic
      between April 2008 and December 2016, 130 patients with 134 nodules were
      included. The relationship between the IAR and VRR was analyzed at six months, 12
      months, and the final follow-up. The relationship between the IAR and final VRR
      was also analyzed according to the initial nodule volumes. RESULTS: The mean VRR
      was 78.7 +/- 17.5% (range 23.3-100%) at a mean follow-up period of 22.6 +/- 20.1
      months (range 3-93 months). The mean IAR was 90.0 +/- 11.6% (range 39.1-100%).
      The correlation coefficient between the IAR and final VRR was 0.65, which
      indicates a positive correlation (p < 0.001). When the IAR exceeded 70%, it
      tended to achieve 50% VRR in most cases. CONCLUSIONS: The IAR is a quantitative
      indicator of how well the RFA procedures are performed, and it is highly
      correlated with the VRR. If the IAR is >70%, VRR of >50% may be expected after
      RFA.

PMID- 30226442
TI  - The Effects of Metabolic Substrate Availability on Human Adipose-Derived Stem
      Cell Spheroid Survival.
AB  - IMPACT STATEMENT: Human adipose-derived stem cells (hADSCs) spheroids have
      displayed remarkable potential for treating ischemic injury. However, low
      nutrient (i.e., glucose and oxygen) availability in ischemic environments results
      in limited tissue viability posttransplantation. To develop an understanding of
      the effects of nutrient availability on spheroid survival, we utilized both in
      vitro and computational models to examine the limiting factors in metabolic
      supply for avascular microtissues, revealing the critical role of glucose to
      improve hADSC spheroid survival in ischemic conditions. These results may impact
      future strategies for improving hADSC transplantation efficacy through codelivery
      of metabolic substrates.

PMID- 30226443
TI  - Persistent/Recurrent Differentiated Thyroid Cancer: Clinical and Radiological
      Characteristics of Persistent Disease and Clinical Recurrence Based on Computed
      Tomography Analysis.
AB  - BACKGROUND: The natural course of persistent/recurrent differentiated thyroid
      cancer (DTC) has not been fully elucidated. The purpose of this study was to
      assess the relative incidence and clinico-radiological characteristics of
      persistent disease and clinical recurrence based on computed tomography (CT)
      analysis in patients with persistent/recurrent DTC. METHODS: From January 2005 to
      December 2016, this retrospective study included 107 patients (M:F = 28:79; Mage
      = 53.5 years) with surgically proven cervical locoregional recurrence of DTC. Two
      neck CT examinations (median interval 1.92 years; range 0.17-7.58 years) before
      the last thyroid cancer surgery within the study period were reevaluated. Based
      on the presence of the lesion on the first CT and its progression on the second
      CT, the locoregional recurrence was classified into the following categories:
      stable persistence (decrease, no change, or increase by <2 mm in short dimension
      on the second CT), progressive persistence (increase by >=2 mm), and clinical
      recurrence (newly appeared on the second CT). Clinical and radiological
      characteristics of the three groups were compared using univariate and
      multivariate logistic regression analyses. RESULTS: The relative incidences of
      stable persistence, progressive persistence, and clinical recurrence were 56.1%
      (60/107), 15.0% (16/107), and 29.0% (31/107), respectively. Multivariate analysis
      between the clinical recurrence (29.0%) and persistence (71.0%) groups revealed
      various independent factors for prediction of clinical recurrence. These included
      longer interval between the two CT examinations (median 2.67 vs. 1.79 years; p =
      0.021), a smaller number of thyroid surgeries (1.16 +/- 0.45 vs. 1.55 +/- 0.81; p
      = 0.002), and a history of neck dissection at the location of the largest
      locoregional recurrence (70.0% vs. 31.4%; p < 0.001). There was no significant
      independent factor for differentiation between the stable persistence (78.9%;
      60/76) and progressive persistence (21.1%; 16/76) groups. The results may have
      been influenced by selection bias because this study included only surgically
      proven cases. CONCLUSIONS: With regard to cervical locoregional recurrence of
      DTC, active surveillance may be favored because more than a half of the cases are
      structurally persistent and stable. However, meticulous evaluation is necessary
      to detect progressive persistence and clinical recurrence, considering various
      clinical factors.

PMID- 30226444
TI  - Comprehensive Transcriptomic and Genomic Profiling of Subtypes of Follicular
      Variant of Papillary Thyroid Carcinoma.
AB  - BACKGROUND: Among subtypes of follicular variant of papillary thyroid carcinoma
      (FVPTC), encapsulated FVPTC (EFVPTC) shows more indolent behavior than
      infiltrative FVPTC (IFVPTC). In particular, noninvasive EFVPTC, now designated as
      noninvasive follicular thyroid neoplasm with papillary-like nuclear features
      (NIFTP), tends to have an excellent prognosis. However, it remains unclear
      whether the molecular pathogenesis or signature of the various forms of FVPTC is
      different. By massively parallel sequencing analysis, this study comprehensively
      characterized the transcriptional and mutational landscape of FVPTC and
      established correlations with phenotypic subtypes. METHODS: This study included
      48 FVPTCs: 17 NIFTPs, 13 invasive EFVPTCs (I-EFVPTCs), and 18 IFVPTCs. For
      comparison, 55 classical papillary thyroid carcinomas (cPTCs) harboring a
      BRAFV600E mutation, six follicular adenomas (FAs), and 15 minimally invasive
      follicular thyroid carcinomas (miFTCs) with RAS mutations were also included.
      RESULTS: In NIFTP, the BRAFV600E mutation was not found, but RAS and other
      alterations were present in 64.7% and 17.6% of cases, respectively. However, in I
      EFVPTC and IFVPTC, the proportions of BRAFV600E mutation (38.5% and 38.9%,
      respectively) and of RAS mutations (38.5% and 38.9%, respectively) or other
      alterations (15.4% and 16.7%, respectively) were similar. On a molecular level,
      RAS-mutated FVPTCs were all RAS-like except for one IFVPTC case. Transcriptomic
      profiles of NIFTP, I-EFVPTC, and FA/miFTC were comparable, although the profile
      of RAS-mutated IFVPTC was altered to activate molecular pathways involved in cell
      adhesion and invasion. Interestingly, 80% of BRAFV600E-mutated I-EFVPTCs were
      also classified as RAS-like, whereas all BRAFV600E-mutated IFVPTCs were BRAF-like
      and indistinguishable from cPTC. Molecular pathways associated with cell adhesion
      and invasion were also differentially activated in BRAFV600E-mutated IFVPTC.
      CONCLUSIONS: Molecular profiles of NIFTP and I-EFVPTC may be shared with
      FA/miFTC, while IFVPTC seems to be associated with a similar profile as cPTC.
      Activation of cell adhesion and invasion pathways may play a key role in the
      development of invasive phenotypes of FVPTC.

PMID- 30226445
TI  - Response to Lenvatinib in Children with Papillary Thyroid Carcinoma.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common thyroid
      malignancy in children and adolescents. Infrequently, children with PTC may
      present with or develop disease not amenable to surgery or radioactive iodine
      (RAI), and systemic therapy may be an option. Lenvatinib is an oral tyrosine
      kinase inhibitor that is approved by the Food and Drug Administration for the
      treatment of adults with locally recurrent or metastatic, progressive, RAI
      refractory well-differentiated thyroid carcinoma. The effect of lenvatinib in
      children with PTC has not been reported. PATIENT FINDINGS: Three children with
      metastatic PTC not amenable or refractory to RAI who responded to lenvatinib are
      reported. All of them developed respiratory distress requiring oxygen caused by
      extensive bilateral metastatic pulmonary disease. The first patient is a 14-year
      old female who was initially treated with sorafenib for extensive PTC not
      amenable to upfront surgery or RAI. She had progressive pulmonary disease after
      five months, and was subsequently treated with oral lenvatinib (14 mg/m2/day).
      She was weaned to room air after eight weeks. The second patient is a 15-year-old
      male who was treated with lenvatinib (14 mg/m2/day) for iodine non-avid diffuse
      pulmonary disease after initial total thyroidectomy and cervical lymph node
      dissection. He was weaned off oxygen in six weeks. The third patient is a five
      year-old male who was treated with lenvatinib (14 mg/m2/day) for pulmonary
      disease progression 24 months after treatment with total thyroidectomy, cervical
      lymph node dissection, and RAI treatment. He was weaned off oxygen one day after
      starting lenvatinib. Two of the patients required dose adjustments secondary to
      proteinuria. Otherwise, all patients tolerated lenvatinib well. The first two
      patients remained clinically stable on lenvatinib 23 months and 11 months after
      initiation of therapy, respectively, and the third patient transitioned to a
      tumor-specific targeted therapy after one month. SUMMARY: Three pediatric
      patients are reported with metastatic PTC not amenable or refractory to RAI who
      achieved a response on lenvatinib. CONCLUSION: Lenvatinib therapy is well
      tolerated and demonstrated clinical activity in children with advanced PTC.
      Lenvatinib should be considered in children with PTC that is refractory or not
      amenable to conventional management.

PMID- 30226446
TI  - Sexual Sadism Among Sex Offenders in Switzerland.
AB  - The Sexual Sadism Scale (SeSaS) was developed to assist in the diagnosis of
      sexual sadism, and it revealed adequate psychometric properties in prior
      research. This study cross validated the SeSaS in Switzerland using a sample of
      179 male sex offenders. Specifically, the SeSaS conformed to a Mokken model of
      double monotonicity (scalability coefficient [ H] = .46, coefficient of
      reproducibility [CR] = .89), indicating that it measures a unidimensional
      construct of sexual sadism with hierarchically ordered items. The reliability of
      the scale was acceptable to high (rho = .80, lambda2 = .75, kappa = .88). In
      addition, the SeSaS was strongly associated with sexual sadism diagnoses based on
      mental health manuals ( rpb = .60, odds ratio [OR] = 13.02, area under the curve
      [AUC] = 1) but not with recidivism. The results suggest that the use of the SeSaS
      may improve the validity and reliability of sexual sadism diagnoses, therefore
      playing a role in the assessment and management of sex offenders.

PMID- 30226447
TI  - Active Surveillance of Low-Risk Papillary Thyroid Microcarcinoma: A Multi-Center
      Cohort Study in Korea.
AB  - BACKGROUND: Active surveillance has been introduced as a management option for
      low-risk papillary thyroid microcarcinoma (PTMC) due to its mostly indolent
      course. METHODS: This was a multicenter study of 370 PTMC patients who underwent
      active surveillance more than one year. The changes in volume and maximum
      diameter between initial and last ultrasonography were evaluated to identify the
      natural course of PTMC during active surveillance. RESULTS: Patients' age at
      diagnosis was 51 +/- 12 years, and 110 (30%) patients were <45 years of age. The
      initial maximum diameter and volume of PTMCs were 5.9 +/- 1.7 mm and 81.0 +/-
      77.7 mm3, respectively. During the median 32.5 months of follow-up, 86 (23.2%)
      patients were found to have an increase in tumor volume, and 13 (3.5%) patients
      showed an increase in the maximal diameter of the tumor. The cumulative incidence
      of volume increase gradually rose with time (6.9%, 17.3%, 28.2%, and 36.2% after
      two, three, four, and five years, respectively). The risk of volume increase in
      patients <45 years of age was twice as high as in older patients (p = 0.002).
      There was no significant difference in tumor size change according to sex,
      levothyroxine treatment, or presence of Hashimoto's thyroiditis. During the
      period, 58 (15.7%) patients underwent delayed thyroid surgery due to anxiety
      (37.9%), tumor size increase (32.8%), or appearance of cervical lymph node
      metastasis (8.6%). Lymph node metastasis was found in 29.3% of patients on
      pathological examination. CONCLUSIONS: A significant number of PTMCs grow during
      active surveillance, and tumor volume change is a more sensitive means of
      evaluating tumor growth. Active surveillance can be carefully applied for
      selected patients. Although it is not contraindicated, it should be applied more
      cautiously for younger patients.

PMID- 30226448
TI  - Breaking up sitting time after stroke (BUST-stroke).
AB  - OBJECTIVES: People with stroke sit for long periods each day, which may
      compromise blood glucose control and increase risk of recurrent stroke. Studies
      in other populations have found regular activity breaks have a significant
      immediate (within-day) positive effect on glucose metabolism. We examined the
      effects of breaking up uninterrupted sitting with frequent, short bouts of light
      intensity physical activity in people with stroke on post-prandial plasma glucose
      and insulin. METHODS: Randomized within-participant crossover trial. We included
      people between 3 months and 10 years post-stroke, ambulant with minimal
      assistance and not taking diabetic medication other than metformin. The three
      experimental conditions (completed in random order) were: sitting for 8 h
      uninterrupted, sitting with 3 min bouts of light-intensity exercise while
      standing every 30 min, or sitting with 3 min of walking every 30 min. Meals were
      standardized and bloods were collected half- to one-hourly via an intravenous
      cannula. RESULTS: A total of 19 participants (9 female, mean [SD] age 68.2
      [10.2]) completed the trial. The majority ( n = 12, 63%) had mild stroke symptoms
      (National Institutes of Stroke Scale score 0-13). There was no significant effect
      of experimental condition on glucose (mean [SD] positive incremental area [+iAUC]
      mmol.L.h-1 under the curve during sitting 42.3 [29.5], standing 47.4 [23.1],
      walking 44.6 [26.5], p = 0.563) or insulin (mean + iAUC pmol.L.h-1 sitting 14,161
      [7,560], standing 14,043 [8,312], walking 14,008 [8,269], p = 0.987). CONCLUSION:
      Frequent, short bouts of light-intensity physical activity did not have a
      significant effect on post-prandial plasma glucose and insulin in this sample of
      people with stroke. Further studies are needed to identify strategies that
      improve inactivity-related glucose metabolism after stroke.

PMID- 30226449
TI  - National and sub-national patterns of mortality from stroke in the Iranian
      population (1990-2015): Complementary results from the NASBOD study.
AB  - Background Iran lacks a population level comprehensive assessment of stroke
      epidemiology. Using data from the NASBOD Study, we estimated the mortality of
      stroke among the Iranian population from 1990 to 2015. Methods Data were
      collected from all the available sources including the national death
      registration system and two major cemeteries. After addressing incompleteness of
      child and adult death data and by using mixed effect model, spatio-temporal model
      and Gaussian Process Regression, levels and trends of child and adult mortality
      were estimated. By considering cause fraction to these estimates; cause specific
      mortality was estimated. In these process wealth index, urbanization, and years
      of schooling were used as covariates. Results In 2015, the age-standardized
      stroke mortality rate due was 47.76 (95% UI: 34.68-65.03) for males and 40.16
      (30.38-5 2.72) for females, per 100,000 population. Stroke occurrence for both
      ischemic and non-ischemic strokes showed decreasing trends in both sexes after
      2001-2002, at national and sub-national levels. The highest and lowest mortality
      rates between provinces ranged from 52.11 (40.3-66.66) to 24.47 (18.71-31.79) in
      men and from 65.51 (47.13-89.41) to 30.43 (21.95-41.82) in women per 100,000
      population. Conclusion Although age-standardized rates of stroke mortality are
      falling, in the past three decades, the absolute number of people who have had a
      stroke has increased. Stroke mortality remains high in Iran.

PMID- 30226450
TI  - 68Ga-PSMA-11 PET: Better at Detecting Prostate Cancer than Multiparametric MRI?

PMID- 30226451
TI  - Challenges in the Diagnosis and Treatment of Spontaneous Intracranial
      Hypotension.

PMID- 30226452
TI  - Is Image-guided Thermal Ablation Ready for Treatment of Stage 1 Non-Small Cell
      Lung Cancer?

PMID- 30226453
TI  - Survival Rates after Thermal Ablation versus Stereotactic Radiation Therapy for
      Stage 1 Non-Small Cell Lung Cancer: A National Cancer Database Study.
AB  - Purpose To compare survival rates of thermal ablation and stereotactic radiation
      therapy (SRT) for stage 1 non-small cell lung cancer (NSCLC). Materials and
      Methods In this retrospective study, patients with stage 1 NSCLC treated by
      thermal ablation (TA) or SRT were identified in the 2004-2013 National Cancer
      Database. Patients who underwent TA and SRT were one-to-one propensity matched to
      undergo thermal ablation. Outcomes were overall survival and unplanned hospital
      readmission within 30 days after treatment. Results This study included 28 834
      patients (TA, 1102 patients; SRT, 27 732 patients). Patients treated with TA had
      more comorbidities (Charlson comorbidity index of 1 vs >=2, 32.8% [362 of 1102]
      vs 19.7% [217 of 1102], respectively) compared with SRT (Charlson comorbidity
      index of 1 vs >=2, 26.9% [7448 of 27 732] vs 15.3% [4251 of 27 732],
      respectively; P , .001) and smaller tumor size (mean tumor size, TA vs SRT: 19 mm
      vs 22 mm, respectively; P , .001). In the propensity score-matched cohort with
      balanced distribution of potential confounders, there was no significant
      difference in overall survival between TA and SRT at a mean follow-up of 52.4
      months (survival difference, P = .69). Overall survival rates were comparable
      between TA and SRT (1 year, 85.4% vs 86.3%, respectively, P = .76; 2 years, 65.2%
      vs 64.5%, respectively, P = .43; 3 years, 47.8% vs 45.9%, respectively, P = .32;
      5 years, 24.6% vs 26.1%, respectively, P = .81). Unplanned hospital readmission
      rates were higher for patients who underwent TA versus those who underwent SRT
      (3.7% [40 of 1070] vs 0.2% [two of 1070], respectively; P , .001). Conclusion
      Regarding overall survival, thermal ablation was noninferior to stereotactic
      radiation therapy for primary treatment of stage 1 non-small cell lung cancer.
      (c) RSNA, 2018 Online supplemental material is available for this article. See
      also the editorial by Shyn in this issue.

PMID- 30226454
TI  - Percutaneous Transcholecystic Removal of Common Bile Duct Stones: Case Series in
      114 Patients.
AB  - Purpose To evaluate the safety and effectiveness of percutaneous transcholecystic
      removal of common bile duct (CBD) stones in 114 patients. Materials and Methods
      This retrospective study was approved by the institutional review board. From
      September 2011 through February 2017, 114 consecutive patients (68 men, 46 women;
      mean age, 73 years) underwent percutaneous transcholecystic removal of CBD
      stones. All patients had acute cholangitis or cholecystitis. Stones were
      extracted through a 12-F sheath by using a Wittich nitinol stone basket uder
      fluoroscopic guidance. Technical success rates, complications, and long-term
      follow-up were evaluated. Results Technical success was achieved in 96 of 114
      (84.2%) patients. In 18 patients, stone removal was unsuccessful due to failure
      of cystic duct cannulation (n = 11), proximal migration of the CBD stone (n = 3),
      multiple CBD stones (n = 3), and low insertion of the cystic duct (n = 1). No
      major procedure-related complications were seen. During the mean follow-up of 644
      days (range, 11-2206 days), CBD stones recurred in 12 patients after a mean of
      884 days (range, 439-1799 days) after the procedure. Conclusion Percutaneous
      transcholecystic removal of common bile duct stones seems to be a safe and
      effective method. (c) RSNA, 2018 Online supplemental material is available for
      this article . See also the editorial by vanSonnenberg and Panchanathan in this
      issue.

PMID- 30226455
TI  - Twenty-four-hour Learning for Residents: Is it Necessary?

PMID- 30226456
TI  - Diagnostic Accuracy of 68Ga-PSMA-11 PET/MRI Compared with Multiparametric MRI in
      the Detection of Prostate Cancer.
AB  - Purpose To compare the diagnostic accuracy of gallium 68 (68Ga)-labeled prostate
      specific membrane antigen (PSMA)-11 PET/MRI with that of multiparametric MRI in
      the detection of prostate cancer. Materials and Methods The authors performed a
      retrospective study of men with biopsy-proven prostate cancer who underwent
      simultaneous 68Ga-PSMA-11 PET/MRI before radical prostatectomy between December
      2015 and June 2017. The reference standard was whole-mount pathologic
      examination. Readers were blinded to radiologic and pathologic findings. Tumor
      localization was based on 30 anatomic regions. Region-specific sensitivity and
      specificity were calculated for PET/MRI and multiparametric MRI by using raw
      stringent and alternative neighboring approaches. Maximum standardized uptake
      value (SUVmax) in the tumor and Prostate Imaging Reporting and Data System (PI
      RADS) version 2 grade were compared with tumor Gleason score. Generalized
      estimating equations were used to estimate population-averaged sensitivity and
      specificity and to determine the association between tumor characteristics and
      SUVmax or PI-RADS score. Results Thirty-two men (median age, 68 years;
      interquartile range: 62-71 years) were imaged. The region-specific sensitivities
      of PET/MRI and multiparametric MRI were 74% (95% confidence interval [CI]: 70%,
      77%) and 50% (95% CI: 45%, 0.54%), respectively, with the alternative neighboring
      approach (P < .001 for both) and 73% (95% CI: 68%, 79%) and 69% (95% CI: 62%,
      75%), respectively, with the population-averaged generalized estimating equation
      (P = .04). Region-specific specificity of PET/MRI was similar to that of
      multiparametric MRI with the alternative neighboring approach (88% [95% CI: 85%,
      91%] vs 90% [95% CI: 87%, 92%], P = .99) and in population-averaged estimates
      (70% [95% CI: 64%, 76%] vs 70% [95% CI: 64%, 75%], P = .99). SUVmax was
      associated with a Gleason score of 7 and higher (odds ratio: 1.71 [95% CI: 1.27,
      2.31], P < .001). Conclusion The sensitivity of gallium 68-labeled prostate
      specific membrane antigen-11 PET/MRI in the detection of prostate cancer is
      better than that of multiparametric MRI. (c) RSNA, 2018 See also the editorial by
      Civelek in this issue.

PMID- 30226457
TI  - Diagnosis Please Certificates of Recognition Awarded to Three Individuals and to
      International and North American Radiology Resident Groups.

PMID- 30226458
TI  - Percutaneous Transcholecystic Management of Choledocholithiasis: A Next Horizon
      for Interventional Radiologists?

PMID- 30226460
TI  - Opioid-associated Acute Hippocampal Injury with Cardiac Arrest.

PMID- 30226459
TI  - Cryptogenic Cerebrospinal Fluid Leaks in Spontaneous Intracranial Hypotension:
      Role of Dynamic CT Myelography.
AB  - Purpose To propose a modified dynamic CT myelographic technique to locate
      cerebrospinal fluid (CSF) leaks, also known as cryptogenic leaks, in patients
      with spontaneous intracranial hypotension (SIH) in whom previous imaging did not
      show the dural breach. Materials and Methods This retrospective analysis included
      74 consecutive patients with SIH and a myelographically proven CSF leak who were
      evaluated between February 2013 and October 2017. In 14 patients, dynamic CT
      myelography in the prone or lateral position showed the exact leakage point after
      unsuccessful previous imaging. During image analysis, the first time point
      showing extrathecal contrast material was defined as the site of dural breach
      point. Results Mean population age was 44 years (range, 25-65 years [nine women;
      mean age, 44 years; age range, 25-65 years] [five men; mean age, 46 years; age
      range, 29-61 years]). All patients had previously undergone spine MRI,
      conventional dynamic myelography, and CT myelography. Subsequent dynamic CT
      myelography covered a mean range of seven vertebral levels. The leak was caused
      by a calcified microspur in 10 patients and by a dural tear at the axilla of a
      spinal nerve root in the remaining four. The mean volume CT dose index of dynamic
      CT myelography was 107 mGy (range, 12-246 mGy), and the mean dose-length product
      was 1347 mGy.cm (range, 550-3750 mGy.cm). Conclusion Dynamic CT myelography is a
      valuable adjunctive tool with which to identify the precise location of a dural
      tear when other examinations are unsuccessful. (c) RSNA, 2018 See also the
      editorial by Dillon in this issue.

PMID- 30226461
TI  - Romboutsia hominis sp. nov., the first human gut-derived representative of the
      genus Romboutsia, isolated from ileostoma effluent.
AB  - A Gram-stain-positive, motile, rod-shaped, obligately anaerobic bacterium,
      designated FRIFIT, was isolated from human ileostoma effluent and characterized.
      On the basis of 16S rRNA gene sequence similarity, strain FRIFIT was most closely
      related to the species Romboutsia ilealis CRIBT (97.7 %), Romboutsia
      lituseburensis DSM 797T (97.6 %) and Romboutsia sedimentorum LAM201T (96.6 %).
      The level of DNA-DNA relatedness between strain FRIFIT and R. ilealis CRIBT was
      13.9+/-3.3 % based on DNA-DNA hybridization. Whole genome sequence-based average
      nucleotide identity between strain FRIFIT and closely related Romboutsia strains
      ranged from 78.4-79.1 %. The genomic DNA G+C content of strain FRIFIT was 27.8
      mol%. The major cellular fatty acids of strain FRIFIT were saturated and
      unsaturated straight-chain C12-C19 fatty acids as well as cyclopropane fatty
      acids, with C16 : 0 being the predominant fatty acid. The polar lipid profile
      comprised five phospholipids and six glycolipids. These results, together with
      differences in phenotypic features, support the proposal that strain FRIFIT
      represents a novel species within the genus Romboutsia, for which the name
      Romboutsiahominis sp. nov. is proposed. The type strain is FRIFIT (=DSM
      28814T=KCTC 15553T).

PMID- 30226462
TI  - Human cytomegalovirus US28 allows dendritic cell exit from lymph nodes.
AB  - Human cytomegalovirus (HCMV) colonizes blood-borne dendritic cells (DCs). They
      express US28, a viral G protein-coupled receptor (GPCR). In vitro functions have
      been described for US28, but how it contributes to host colonization has been
      unclear. The murine CMV (MCMV) M33 GPCR promotes DC recirculation. We show that
      US28 shares this function. Thus, DC recirculation is also available to HCMV via
      US28, and inhibiting US28 G protein-dependent signalling has the potential to
      reduce systemic infection. We show that M33 also promotes systemic infection
      through infected DC extravasation.

PMID- 30226463
TI  - Salibacterium nitratireducens sp. nov., a haloalkalitolerant bacterium isolated
      from a water sample from Sambhar salt lake, India.
AB  - A strictly aerobic, haloalkali-tolerant, Gram-stain-positive, non-motile, rod
      shaped bacterium, designated strain SMB4T, was isolated from a water sample
      collected from Sambhar salt lake, Rajasthan, India. Growth occurred at 25-50 
      degrees C, 4-12 % (w/v) NaCl and pH of 5-9. Strain SMB4T was positive for beta
      galactosidase, oxidase, catalase and urease activities. The fatty acids were
      dominated by branched forms of fatty acids with iso- and anteiso-saturated fatty
      acids, with a high abundance of anteiso-C15 : 0, anteiso-C17 : 0 and C18 : 0. The
      cell-wall peptidoglycan of strain SMB4T contained meso-diaminopimelic acid, while
      the polar lipids included diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, one unidentified phospholipid and three unidentified
      lipids. The DNA G+C content of strain SMB4T was 49.1 mol%. A blast sequence
      similarity search based on 16S rRNA gene sequence indicated that Salibacterium
      halochares, Salibacterium halotolerans and Salibacterium qingdaonense were the
      nearest phylogenetic neighbours, with a pair-wise sequence similarities of 98.4,
      98.2 and 97.0 % respectively. Phylogenetic analysis showed that strain SMB4T was
      clustered with S. halochares and together clustered with S. halotolerans and S.
      qingdaonense. DNA-DNA hybridization of strain SMB4T with S. halochares DSM
      21373T, S. halotolerans S7T and S. quigdaonense DSM 21621T showed a relatedness
      values of only 39.8, 26.3 and 42.8 %, respectively. Based on its phenotypic
      characteristics and on phylogenetic inference, strain SMB4T represents a novel
      species of the genus Salibacterium, for which the name Salibacterium
      nitratireducens sp. nov. is proposed. The type strain is SMB4T (=MTCC 12633T=KCTC
      33876T=JCM 32187T).

PMID- 30226464
TI  - Lactobacillus paragasseri sp. nov., a sister taxon of Lactobacillus gasseri,
      based on whole-genome sequence analyses.
AB  - Three strains, JCM 5343T, JCM 5344 and JCM 1130, currently identified as
      Lactobacillus gasseri, were investigated using a polyphasic taxonomic approach.
      Although these strains shared high 16S rRNA gene sequence similarities with L.
      gasseri ATCC 33323T (99.9 %), they formed a clade clearly distinct from ATCC
      33323T based on whole-genome relatedness. The average nucleotide identity and in
      silico DNA-DNA hybridization values of these three strains compared to L. gasseri
      ATCC 33323T were 93.4-93.7 and 53.1-54.1 %, respectively, and both were less than
      the widely accepted threshold to distinguish two species (95 and 70 %,
      respectively). The three strains were Gram-stain positive, non-motile, non-spore
      forming, catalase-negative and rod-shaped bacteria. They grew at 25-45  degrees C
      and in the presence of 2.0 % (w/v) NaCl. The major fatty acids of the three
      strains were C16 : 0 and C18 : 1 omega9c. Based on phylogenetic analyses of the
      phenylalanyl-tRNA synthase alpha subunit and RNA polymerase alpha subunit genes,
      and on phenotypic and chemotaxonomic characteristics, strains JCM 5343T, JCM 5344
      and JCM 1130 represent a novel species distinct from L. gasseri, for which we
      propose the name Lactobacillusparagasseri sp. nov. In addition, a large portion
      of genomes currently labelled as L. gasseri in the public sequence database
      should be reclassified as L. paragasseri based on whole-genome relatedness.

PMID- 30226465
TI  - Anisotropic growth is achieved through the additive mechanical effect of material
      anisotropy and elastic asymmetry.
AB  - Fast directional growth is a necessity for the young seedling; after germination,
      it needs to quickly penetrate the soil to begin its autotrophic life. In most
      dicot plants, this rapid escape is due to the anisotropic elongation of the
      hypocotyl, the columnar organ between the root and the shoot meristems.
      Anisotropic growth is common in plant organs and is canonically attributed to
      cell wall anisotropy produced by oriented cellulose fibers. Recently, a mechanism
      based on asymmetric pectin-based cell wall elasticity has been proposed. Here we
      present a harmonizing model for anisotropic growth control in the dark-grown
      Arabidopsis thaliana hypocotyl: basic anisotropic information is provided by
      cellulose orientation) and additive anisotropic information is provided by pectin
      based elastic asymmetry in the epidermis. We quantitatively show that hypocotyl
      elongation is anisotropic starting at germination. We present experimental
      evidence for pectin biochemical differences and wall mechanics providing
      important growth regulation in the hypocotyl. Lastly, our in silico modelling
      experiments indicate an additive collaboration between pectin biochemistry and
      cellulose orientation in promoting anisotropic growth.

PMID- 30226466
TI  - Genetic predisposition to uterine leiomyoma is determined by loci for
      genitourinary development and genome stability.
AB  - Uterine leiomyomas (ULs) are benign tumors that are a major burden to women's
      health. A genome-wide association study on 15,453 UL cases and 392,628 controls
      was performed, followed by replication of the genomic risk in six cohorts.
      Effects of the risk alleles were evaluated in view of molecular and clinical
      characteristics. 22 loci displayed a genome-wide significant association. The
      likely predisposition genes could be grouped to two biological processes. Genes
      involved in genome stability were represented by TERT, TERC, OBFC1 - highlighting
      the role of telomere maintenance - TP53 and ATM. Genes involved in genitourinary
      development, WNT4, WT1, SALL1, MED12, ESR1, GREB1, FOXO1, DMRT1 and uterine stem
      cell marker antigen CD44, formed another strong subgroup. The combined risk
      contributed by the 22 loci was associated with MED12 mutation-positive tumors.
      The findings link genes for uterine development and genetic stability to
      leiomyomagenesis, and in part explain the more frequent occurrence of UL in women
      of African origin.

PMID- 30226467
TI  - Normal cognitive and social development require posterior cerebellar activity.
AB  - Cognitive and social capacities require postnatal experience, yet the pathways by
      which experience guides development are unknown. Here we show that the normal
      development of motor and nonmotor capacities requires cerebellar activity. Using
      chemogenetic perturbation of molecular layer interneurons to attenuate cerebellar
      output in mice, we found that activity of posterior regions in juvenile life
      modulates adult expression of eyeblink conditioning (paravermal lobule VI, crus
      I), reversal learning (lobule VI), persistive behavior and novelty-seeking
      (lobule VII), and social preference (crus I/II). Perturbation in adult life
      altered only a subset of phenotypes. Both adult and juvenile disruption left gait
      metrics largely unaffected. Contributions to phenotypes increased with the amount
      of lobule inactivated. Using an anterograde transsynaptic tracer, we found that
      posterior cerebellum made strong connections with prelimbic, orbitofrontal, and
      anterior cingulate cortex. These findings provide anatomical substrates for the
      clinical observation that cerebellar injury increases the risk of autism.

PMID- 30226469
TI  - A multi-criteria optimization approach for HDR prostate brachytherapy: II.
      Benchmark against clinical plans.
AB  - The current iterative approach to inverse planning of high dose rate treatment
      planning can be time consuming. The purpose of this two-part study is to
      streamline the planning process while maintaining plan quality. In this second
      part, a multi-criteria optimization (MCO) planning algorithm is proposed and
      benchmarked against a standard planning algorithm. With a set of previously
      established regression models, a patient-specific valid solution space on the
      Pareto surface was predicted based on the anchor plans results. Alternative plans
      generated alongside the partial Pareto front were presented to the planner, and
      one plan was selected as the MCO plan. The dosimetric parameters results as well
      as the planning time were compared between the MCO plans and the physician
      approved standard plans for 236 prostate cases. Results show that the urethra is
      better spared with MCO planning than with standard planning (a lower mean
      urethral D 10 value of 2.25%). The overall MCO plan quality also outperforms the
      standard plan quality, since MCO planning is able to increase the frequency of
      clinically acceptable plans meeting all of RTOG criteria simultaneously without
      any human intervention (from 83.05% to 97.46%). Finally, the average MCO planning
      time is [Formula: see text] without any interventions of treatment planners. The
      presented MCO planning algorithm constitutes a robust and automated way to
      improve treatment quality in brachytherapy.

PMID- 30226468
TI  - Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits
      pronounced skeletal toxicity.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder
      characterized by debilitating heterotopic ossification (HO). The retinoic acid
      receptor gamma agonist, palovarotene, and antibody-mediated activin A blockade
      have entered human clinical trials, but how these therapeutic modalities affect
      the behavior of pathogenic fibro/adipogenic progenitors (FAPs) is unclear. Using
      live-animal luminescence imaging, we show that transplanted pathogenic FAPs
      undergo rapid initial expansion, with peak number strongly correlating with HO
      severity. Palovarotene significantly reduced expansion of pathogenic FAPs, but
      was less effective than activin A inhibition, which restored wild-type population
      growth dynamics to FAPs. Palovarotene pretreatment did not reduce FAPs'
      skeletogenic potential, indicating that efficacy requires chronic administration.
      Although palovarotene inhibited chondrogenic differentiation in vitro and reduced
      HO in juvenile FOP mice, daily dosing resulted in aggressive synovial joint
      overgrowth and long bone growth plate ablation. These results highlight the
      challenge of inhibiting pathological bone formation prior to skeletal maturation.

PMID- 30226470
TI  - Application of reduced sensor movement sequences as a precursor for search area
      partitioning and a selection of discrete EEV contour-ring fragments for active
      electrolocation.
AB  - In addition to their visual sense, weakly electric fish use active
      electrolocation to detect and analyse objects in their nearby environment. Their
      ability to generate and sense electric fields combined with scanning-like
      swimming movements are intended to extract further parameters like the size,
      shape and material properties of objects. Inspired by this biological example,
      this work introduces an application for active electrolocation based on reduced
      sensor movement sequences as presented in Wolf-Homeyer et al (2016 Bioinspir.
      Biomim. 11 055002). Initially, the application is conducted with a simulated
      receptor-system consisting of an emitter-dipole and an orthogonally arranged pair
      of sensor-electrodes. Close inspection of a minimal set of scanning movements
      allows the exclusion of sectors of the general search area early in the proposed
      localization algorithm (search area partitioning). Furthermore, the proposed
      algorithm is based on an analytical representation of the electric field and of
      the so-called EEV (ensemble of electrosensory viewpoints) (Solberg et al 2008
      Int. J. Robot. Res. 27 529-48) rather than using computationally expensive FEM
      simulations, rendering it suitable for embedded computer systems. Two-dimensional
      discrete EEV contour-ring points (CRPs) of desired accuracy are extracted. In the
      core of the localization algorithm, fragments of the EEV are selected from valid
      sectors of the search area, which generates sets of CRPs, one for each sensor
      emitter position/orientation. These sets are investigated by means of a nearness
      metric to find points in different sets which correspond to each other in order
      to estimate the object position. Two resultant scanning strategies/localization
      algorithms are introduced.

PMID- 30226471
TI  - Enhanced performance of hybrid self-biased heterojunction photodetector on soft
      lithographically patterned organic platform.
AB  - Nanopatterning of the active layer with feature size comparable to the wavelength
      of visible light is a popular strategy for improving the performance of
      optoelectronic devices, as these structures enhance the optical path length by
      light trapping due to combined contribution of multiple scattering, diffraction,
      and antireflection. Here, we report the fabrication of ZnO/CdS self-biased
      heterojunction photodetectors on soft lithographically patterned PEDOT:PSS layers
      with grating geometry. The present study combines the robustness of inorganic
      devices along with the convenience of easy patterning capability of an organic
      PEDOT:PSS layer. Patterns with two different line widths (L P = 350 nm, and Lp =
      750 nm) have been used in this study to understand the influence of feature
      dimension on the device performance. We observe enhanced photoluminescence on
      patterned devices, in comparison to devices fabricated on flat PEDOT:PSS films,
      which is attributed to the increased interfacial area between the organic and
      inorganic layers. The spectral response [R( lambda )] and specific detectivity [D
      * ( lambda )] are found to be higher for the devices with Lp = 350 nm as compared
      to other devices due to enhanced absorption within the structures due to
      confinement of light, which also results in reduced reflectance in devices with
      Lp = 350 nm.

PMID- 30226472
TI  - A multi-criteria optimization approach for HDR prostate brachytherapy: I. Pareto
      surface approximation.
AB  - High dose rate (HDR) brachytherapy planning usually involves an iterative process
      of refining planning objectives until a clinically acceptable plan is produced.
      The purpose of this two-part study is to improve current planning practice by
      designing a novel inverse planning algorithm based on multi-criteria optimization
      (MCO). In the first part, complete Pareto surfaces were approximated and studied
      for prostate cases. A Pareto surface approximation algorithm was implemented
      within the framework of Inverse Planning Simulated Annealing. The Pareto surfaces
      of 140 prostate cases were approximated with the proposed MCO algorithm. For each
      case, the Pareto surface was represented by automatically generating 300 Pareto
      optimal plans, and the clinically acceptable region was identified. Thus, 42 000
      Pareto optimal plans were created to characterize Pareto surfaces for all the
      cases. In addition, the relationship between the clinically acceptable region and
      four anchor plans was studied. As a result, a set of polynomial regression models
      was extracted to rapidly predict the clinically acceptable region on the Pareto
      surface based on anchor plans. Pareto surfaces for HDR brachytherapy prostate
      cases were well characterized in this study. The proposed regression models may
      help define the most relevant solution phase space.

PMID- 30226473
TI  - A carnosine analog mitigates metabolic disorders of obesity by reducing carbonyl
      stress.
AB  - Sugar- and lipid-derived aldehydes are reactive carbonyl species (RCS) frequently
      used as surrogate markers of oxidative stress in obesity. A pathogenic role for
      RCS in metabolic diseases of obesity remains controversial, however, partly
      because of their highly diffuse and broad reactivity and the lack of specific RCS
      scavenging therapies. Naturally occurring histidine dipeptides (e.g., anserine
      and carnosine) show RCS reactivity, but their therapeutic potential in humans is
      limited by serum carnosinases. Here, we present the rational design,
      characterization, and pharmacological evaluation of carnosinol, i.e., (2S)-2-(3
      amino propanoylamino)-3-(1H-imidazol-5-yl)propanol, a derivative of carnosine
      with high oral bioavailability that is resistant to carnosinases. Carnosinol
      displayed a suitable ADMET (absorption, distribution, metabolism, excretion, and
      toxicity) profile and was determined to have the greatest potency and selectivity
      toward alpha,beta-unsaturated aldehydes (e.g., 4-hydroxynonenal, HNE, ACR) among
      all others reported thus far. In rodent models of diet-induced obesity and
      metabolic syndrome, carnosinol dose-dependently attenuated HNE adduct formation
      in liver and skeletal muscle, while simultaneously mitigating inflammation,
      dyslipidemia, insulin resistance, and steatohepatitis. These improvements in
      metabolic parameters with carnosinol were not due to changes in energy
      expenditure, physical activity, adiposity, or body weight. Collectively, our
      findings illustrate a pathogenic role for RCS in obesity-related metabolic
      disorders and provide validation for a promising new class of carbonyl-scavenging
      therapeutic compounds rationally derived from carnosine.

PMID- 30226474
TI  - Rho-kinase/AMPK axis regulates hepatic lipogenesis during overnutrition.
AB  - Obesity is a major risk factor for developing nonalcoholic fatty liver disease
      (NAFLD). NAFLD is the most common form of chronic liver disease and is closely
      associated with insulin resistance, ultimately leading to cirrhosis and
      hepatocellular carcinoma. However, knowledge of the intracellular regulators of
      obesity-linked fatty liver disease remains incomplete. Here we showed that
      hepatic Rho-kinase 1 (ROCK1) drives obesity-induced steatosis in mice through
      stimulation of de novo lipogenesis. Mice lacking ROCK1 in the liver were
      resistant to diet-induced obesity owing to increased energy expenditure and
      thermogenic gene expression. Constitutive expression of hepatic ROCK1 was
      sufficient to promote adiposity, insulin resistance, and hepatic lipid
      accumulation in mice fed a high-fat diet. Correspondingly, liver-specific ROCK1
      deletion prevented the development of severe hepatic steatosis and reduced
      hyperglycemia in obese diabetic (ob/ob) mice. Of pathophysiological significance,
      hepatic ROCK1 was markedly upregulated in humans with fatty liver disease and
      correlated with risk factors clustering around NAFLD and insulin resistance.
      Mechanistically, we found that hepatic ROCK1 suppresses AMPK activity and a
      ROCK1/AMPK pathway is necessary to mediate cannabinoid-induced lipogenesis in the
      liver. Furthermore, treatment with metformin, the most widely used antidiabetes
      drug, reduced hepatic lipid accumulation by inactivating ROCK1, resulting in
      activation of AMPK downstream signaling. Taken together, our findings establish a
      ROCK1/AMPK signaling axis that regulates de novo lipogenesis, providing a unique
      target for treating obesity-related metabolic disorders such as NAFLD.

PMID- 30226475
TI  - Toenail concentrations of zinc, selenium and nickel in patients with chronic
      recurrent warts: A pilot two-group comparative study.
AB  - Background: Normal immune functioning requires sufficient levels of trace
      elements including zinc and selenium, while elements such as nickel can be
      immunotoxic. Aim: To assess long-term abnormalities in zinc, selenium and nickel
      levels in patients with chronic recurrent warts. Methods: Toenail samples were
      taken from 28 patients with chronic recurrent warts and 30 apparently healthy
      matching controls were analysed. Toenail concentrations of zinc, selenium and
      nickel were measured using inductively-coupled plasma-optical emission
      spectroscopy. Results: Selenium levels were significantly higher in patients than
      in controls (P = 0.03). Levels of trace elements did not correlate with the
      number or duration of warts. Toenail nickel levels in all subjects were higher
      than globally reported values. Limitations: A small sample size and the absence
      of regional reference ranges for concentrations of trace elements in toenails.
      Conclusion: Zinc does not seem to be involved in the chronicity of warts, and it
      is unclear if selenium has a protective role against warts. Our finding of high
      concentrations of nickel in both patients and controls raises concerns about
      environmental exposure.

PMID- 30226476
TI  - Vismodegib treatment in a HIV positive patient on antiretroviral therapy.

PMID- 30226477
TI  - Slowly growing nodule in supralabial region.

PMID- 30226478
TI  - Linking of psoriasis with osteopenia and osteoporosis: A cross-sectional study.
AB  - Background/Purpose: Psoriasis is a multisystem disease which has been related to
      vitamin-D deficiency through chronic inflammation. This psoriasis-related
      inflammatory state and vitamin-D deficiency may induce bone mineral density loss.
      The purpose of this study is to assess the relationship of psoriasis with bone
      mineral density, by comparing psoriatic patients with healthy controls and
      patients with osteopenia/osteoporosis. Methods: A total of 185 subjects were
      studied; 58 psoriatic patients who had not been under systemic or biological
      treatment were included. Age, gender, body mass index, phosphocalcic metabolic
      parameters and hip and lumbar (L4) bone mineral density data were collected.
      These variables were compared with those collected in 61 healthy controls and 67
      patients with osteopenia/osteoporosis. Results: Psoriatic patients showed worse
      hip and lumbar spine bone mineral density levels than healthy controls (P =
      0.001) and better levels than osteoporotic patients (P < 0.001). Multivariate
      analysis demonstrated a negative association of age and a positive association of
      body mass index in hip bone mineral density in psoriatic patients. Limitations:
      The main limitations are those of cross-sectional studies, such as a lack of
      follow up period, and a male predominance in the psoriatic group, which is
      corrected employing a multivariate analysis with an adjusted model for
      confounding factors. Conclusions: Bone mineral density levels in psoriatic
      patients are situated halfway between healthy controls and patients with
      osteopenia/osteoporosis. In addition, the higher body mass index in patients with
      psoriasis appears to confer a protective effect against further development of
      lower bone mineral density.

PMID- 30226479
TI  - Adult teratoid Wilm's tumor - a diagnostic dilemma.

PMID- 30226480
TI  - Water exchange versus air insufflation for colonoscopy: A meta-analysis.
AB  - Background/Aims: To compare water exchange (WE) method with conventional air
      insufflation (AI) method for colonoscopy, evaluating the technical quality,
      screening efficacy, and patients' acceptance. Materials and Methods: Electronic
      databases were systematically searched for randomized controlled trials comparing
      WE colonoscopy with AI colonoscopy. The pooled data of procedure-associated and
      patient-related outcomes were assessed, using the weighted mean difference (WMD)
      with 95% confidence interval (CI) for continuous variables and relative risk (RR)
      with 95% CI for dichotomous variables, respectively. Results: A total of 13
      studies involving 7056 patients were included. The cecum intubation rate was
      similar between WE and AI methods (RR = 1.01, 95% CI = 0.99-1.02,P = 0.37);
      however, a significantly longer cecum intubation time was shown in WE group (WMD
      = 1.56, 95% CI = 0.75-2.37,P = 0.002). Compared with AI, WE was associated with a
      higher risk of adenoma detection rate (ADR) (RR = 1.28, 95% CI = 1.18-1.38,P <
      0.00001) and polyp detection rate (PDR) (RR = 1.30, 95% CI = 1.21-1.39,P <
      0.00001). Patients in WE group experienced significantly less maximum pain score
      (WMD = -1.99, 95% CI = -2.68 to -1.30,P < 0.00001) and less requested on-demand
      sedation (RR = 0.58, 95% CI = 0.44-0.77,P = 0.0002). Likewise, they also
      experienced less abdominal compression (RR = 0.62, 95% CI = 0.51-0.74,P <
      0.00001) and reposition (RR = 0.74, 95% CI = 0.63-0.86,P = 0.0001). Moreover,
      patients' willingness to repeat colonoscopy was significantly greater for WE (RR
      = 1.14, 95% CI = 1.07-1.21,P < 0.0001). Conclusion: This meta-analysis confirmed
      that WE method could significantly increase ADR/PDR and improve patients'
      acceptance of colonoscopy, while reducing the degree of pain and minimize the
      need for on-demand sedation and adjunct maneuvers, despite requiring more cecal
      intubation time.

PMID- 30226481
TI  - Low expression of MUC2 is associated with longer disease-free survival in
      patients with colorectal carcinoma.
AB  - Background/Aim: The objective of this study was to investigate the relationship
      between MUC2 immunostaining and clinicopathological characteristics in a subset
      of colorectal carcinomas (CRCs). Materials and Methods: A total of 128 CRCs, 50
      local nodal metastases, and 42 normal colonic mucosae were retrieved from the
      archives at the Department of Pathology at King Abdulaziz University, Jeddah,
      Saudi Arabia. Immunohistochemistry was performed using anti-MUC2 antibody. A cut
      off of 25% of positive immunostaining was used to define low and high
      immunostaining. Statistical tests were used to determine the association of MUC2
      with clinicopathological characteristics and survival. Results: MUC2
      immunostaining was observed in 66.7% in normal colonic mucosa. Low MUC2
      immunostaining was higher in primary CRC (P = 0.003) and nodal metastasis (80%)
      (P < 0.001). There was significant association of low MUC2 immunostaining in CRC
      with age group below 60 years (P = 0.05) and occurrence of lymphovascular
      invasion (P = 0.034). Other clinicopathological parameters were not correlated
      with MUC2 immunostaining. Regression analysis revealed that low MUC2
      immunostaining was an independent predictor of lymphovascular invasion (P =
      0.041). In the Kaplan-Meier survival analysis, there was a significant longer
      disease-free survival in patients with low MUC2 immunostaining (P = 0.045).
      However, there was no association between MUC2 immunostaining and overall
      survival (P = 0.601). Conclusion: MUC2 immunostaining may have distinct clinical
      significance and provide valuable information and could be considered as an
      important independent prognostic factor while planning the adjuvant therapy in
      CRC. In future perspective, characterization of MUC2 immunostaining on a large
      number of cases and molecular studies may be needed.

PMID- 30226482
TI  - A meta-analysis of early oral refeeding and quickly increased diet for patients
      with mild acute pancreatitis.
AB  - Background/Aim: The objective of the study is to clarify whether early oral
      refeeding (EORF) and quickly increasing diet (QID) are of benefit to patients
      with mild acute pancreatitis compared with a traditional oral refeeding strategy.
      Materials and Methods: Studies were searched in PubMed, Cochrane library,
      ScienceDirect, SpringerLink, China Biology Medicine disc and Embase. A meta
      analysis was then performed, using relapse of abdominal pain, nausea/vomiting,
      and length of hospital stay (LOHS) as the evaluation indices. Results: Eight
      trials met the inclusion criteria. For the oral refeeding time group, EORF could
      significantly decrease the LOHS (mean deviation [MD] -1.97; 95% confidence
      interval (CI) -3.32 to -0.62;P = 0.004), and there was no significant difference
      for relapse of abdominal pain (relative risk [RR] 1.17; 95% CI 0.69-2.00;P =
      0.56) or nausea/vomiting (RR 1.30; 95% CI 0.19-8.82;P = 0.79) when compared with
      conventional oral refeeding. For the oral refeeding material group, there was no
      significant difference for relapse of abdominal pain (RR 0.86; 95% CI 0.53-1.40;P
      = 0.54), nausea/vomiting (risk difference -0.01; 95% CI -0.19-0.18;P = 0.94), or
      LOHS (MD -0.88; 95% CI -2.24-0.48;P = 0.20) between the QID and stepwise
      increasing diet groups. Conclusion: Pure EORF or QID caused no damage to patients
      with mild acute pancreatitis, and EORF could significantly decrease the LOHS.

PMID- 30226483
TI  - Survey of local impacts of biofuel crop production and adoption of ethanol stoves
      in southern Africa.
AB  - The two datasets outlined in this paper contain information related to (a) the
      local impacts of biofuel feedstock production, and (b) the factors that influence
      the adoption and/or sustained use of ethanol stoves in southern Africa. The first
      dataset was generated through extensive household surveys around four operational
      jatropha and sugarcane production sites in Malawi, Mozambique, and Swaziland.
      This project aimed to examine the local impacts of the most prominent modes of
      existing or intended biofuel feedstock production in southern Africa. The
      resulting dataset contains information about impacts on rural livelihoods,
      ecosystem services, food security and poverty alleviation. The second dataset is
      the outcome of research into factors that influence the adoption and sustained
      use of ethanol stoves. This dataset was collected through a household survey in
      Maputo city where the only large-scale ethanol stove dissemination programme in
      Africa has been implemented.

PMID- 30226484
TI  - Time-lapse confocal imaging datasets to assess structural and dynamic properties
      of subcellular nanostructures.
AB  - Time-lapse optical microscopy datasets from living cells can potentially afford
      an enormous amount of quantitative information on the relevant structural and
      dynamic properties of sub-cellular organelles/structures, provided that both the
      spatial and temporal dimensions are properly sampled during the experiment. Here
      we provide exemplary live-cell, time-lapse confocal imaging datasets
      corresponding to three sub-cellular structures of the endo-lysosomal pathway,
      i.e. early endosomes, late endosomes and lysosomes, along with detailed
      guidelines to produce analogous experiments. Validation of the datasets is
      conducted by means of established analytical tools to extract the structural and
      dynamic properties at the sub-cellular scale, such as Single Particle Tracking
      (SPT) and imaging derived Mean Square Displacement (iMSD) analyses. In our aim,
      the present work would help other researchers in the field to reuse the provided
      datasets for their own scopes, and to combine their creative approaches/analyses
      to similar acquisitions.

PMID- 30226485
TI  - [Utilidad de la proteina C reactiva en el diagnostico oportuno de fuga de
      anastomosis en cirugia colorrectal].
AB  - Introduccion: La fuga de anastomosis (FA) en cirugia colorrectal es una
      complicacion temida por el incremento de la morbimortalidad. La tasa de FA se
      reporta desde el 1 hasta el 25%. Realizar el diagnostico de forma temprana es
      dificil. Objetivo: Determinar el rendimiento diagnostico de la proteina C
      reactiva (PCR) en una cohorte de pacientes sometidos a cirugia colorrectal
      electiva con anastomosis. Metodo: Se realizo un estudio prospectivo, comparativo,
      en 138 pacientes sometidos a cirugia colorrectal con anastomosis de forma
      electiva, analizando los valores sericos de la PCR los dias 1, 3, 5 y 7 del
      posoperatorio, asi como los de leucocitos y otros datos de sepsis abdominal.
      Resultados: La tasa de FA fue del 6.5%, y los valores de la PCR fueron
      significativamente mas altos en el grupo de pacientes con FA en el tercer dia del
      posoperatorio. Con un punto de corte de 18.5 mg/dl en el tercer dia del
      posoperatorio se obtuvo una sensibilidad del 81%, una especificidad del 91%, un
      valor predictivo positivo del 45% y un valor predictivo negativo del 98%.
      Conclusion: La medicion de la PCR en el tercer dia del posoperatorio en pacientes
      sometidos a cirugia colorrectal electiva con anastomosis primaria o secundaria
      permite identificar las complicaciones septicas, incluida la FA. Introduction:
      The anastomotic leakage (AL) in colorectal surgery is a complication feared by
      the increase in morbidity and mortality. The rate of AF is reported from 1 to
      25%. Making the diagnosis early is difficult. Objective: To determine the
      diagnostic performance of the C reactive protein (CRP) in a cohort of patients
      undergoing elective colorectal surgery with anastomosis. Method: A prospective,
      comparative study was conducted in 138 patients undergoing elective anastomosis
      with colorectal surgery, analyzing the serum values of CRP on postoperative days
      1, 3, 5 and 7, as well as leukocytes and other abdominal sepsis data. Results:
      The AL rate was 6.5%, the CRP values were significantly higher in the group of
      patients with AF on the 3rd postoperative day; with a cut-off point of 18.5 mg/dl
      on the third postoperative day, it obtained sensitivity 81%, specificity 91%,
      positive predictive value 45%, negative predictive value 98%. Conclusion:
      Measurement of CRP on the third postoperative day in patients undergoing elective
      colorectal surgery with primary or secondary anastomosis allows the
      identification of septic complications including leakage of anastomosis.

PMID- 30226486
TI  - [Efecto de un Plan de Mejora de Calidad y Seguridad Clinica en la incidencia de
      infeccion de sitio quirurgico en apendicectomia. Estudio cuasi-experimental].
AB  - Objetivo: Las infecciones de sitio quirurgico se pueden evitar y los programas de
      control basados en paquetes de medidas preventivas son eficaces para reducir su
      incidencia. El objetivo de este estudio fue evaluar el efecto de un Plan de
      Mejora de Calidad y Seguridad Clinica del paciente intervenido de apendicectomia
      en la incidencia de infeccion del sitio quirurgico. Metodo: Se realizo un estudio
      cuasi-experimental con analisis antes y despues de la introduccion de un Plan de
      Calidad y Seguridad Clinica. Se incluyeron pacientes intervenidos de
      apendicectomia. Se estudio la incidencia de infeccion del sitio quirurgico
      durante los 30 dias posteriores a la cirugia (periodo maximo de incubacion de
      infeccion quirurgica). Se evaluo el efecto de la intervencion con la odds ratio
      (OR) ajustada con un modelo de regresion logistica. Resultados: Se incluyeron 606
      pacientes, 267 en el periodo 2009-2010 (antes del plan) y 339 durante 2012-2013
      (despues del plan). La incidencia de infeccion del sitio quirurgico descendio
      despues del plan del 6 al 5.6% (OR: 0.72; intervalo de confianza del 95%: 0.33
      1.56; p = 0.839). Hubo mayor cumplimiento de la profilaxis antibiotica, de la
      preparacion prequirurgica y de la adherencia a la higiene de manos tras la
      introduccion de las medidas. Conclusiones: Aunque la reduccion de la incidencia
      de infeccion del sitio quirurgico no presento diferencias estadisticamente
      significativas tras las medidas adoptadas, se ha conseguido mejorar la
      administracion de la profilaxis antibiotica, la adherencia a la higiene de manos
      y la preparacion prequirurgica. Objective: Surgical site infections can be
      prevented. Control programs based on care bundle have proven to be effective in
      reducing its incidence. The objective of this study was to assess the
      effectiveness of a Plan for Quality Improvement and Clinical Safety in preventing
      the incidence of surgical site infection in patients undergoing appendectomy.
      Method: A quasi-experimental study was designed for analysis before and after the
      introduction of a Plan for Quality and Clinical Safety. Patients undergoing
      appendectomy were included. The incidence of surgical site infection was studied
      within 30 days from the time of surgery (maximum incubation period of surgical
      site infection). The effectiveness of the intervention was evaluated using the
      odds ratio (OR) adjusted with a logistic regression model. Results: A total of
      606 patients were included, of which 267 were operated in the period 2009-2010
      (before the plan) and 339 in 2012-2013 (after the plan). The incidence of
      surgical site -infection decreased after the plan from 6 to 5.6% (OR: 0.72; 95%
      confidence interval: 0.33-1.56; p = 0.839). There was greater compliance of
      antibiotic prophylaxis, preoperative preparation and adherence to hand hygiene
      after the introduction of the measures. Conclusions: Although the reduction in
      the incidence of surgical site infection after the measures adopted did not show
      statistical significant differences, important progress has been made in the
      compliance of antibiotic prophylaxis, adherence to hand hygiene and in the
      preoperative preparation.

PMID- 30226487
TI  - [La asistencia privada en el Sistema Nacional de Salud].

PMID- 30226488
TI  - [Polymetastatic highly aggressive Small Cell Undifferentiated Neuroendocrine
      Carcinoma of Ascending Colon].
AB  - Neuroendocrine carcinoma (NEC) of the colon is a rare and very aggressive tumor
      with poor prognosis. The current case report presents a 53-year-old male with a 6
      cm * 10 cm ascending colon carcinoma, causing large intestine obstruction, with
      simultaneous multiple hepatic metastases and peritoneal carcinomatosis. Surgical
      resection of the primary tumor was performed, because of the bowel obstruction,
      to ameliorate the symptoms before the onset of chemotherapy. Histopathology
      revealed that the tumor was a small-cell undifferentiated NEC. During the
      post0operative period, the patient presented pulmonary metastases, and on the
      36th post-operative day, death occurred due to respiratory failure.

PMID- 30226489
TI  - [Linfoma anaplasico de celulas grandes asociado a implantes mamarios. Importancia
      para el cirujano].
AB  - El linfoma anaplasico de celulas grandes asociado a implantes mamarios (BIA-ALCL,
      breast implant associated-anaplastic large cell lymphoma) es una enfermedad
      infrecuente, pero el numero de casos ha aumentado en los ultimos anos. Se puede
      presentar en la consulta del cirujano como un aumento del volumen mamario por
      derrame periprotesico o como masa capsular. El tratamiento de eleccion es la
      cirugia, con explante de las protesis y exeresis de la capsula periprotesica. El
      pronostico, si el diagnostico es precoz y el tratamiento es adecuado, es bueno.
      El objetivo del presente trabajo fue revisar la literatura cientifica existente
      hasta la fecha sobre el BIA-ALCL y poner de manifiesto la importancia que este
      tipo de neoplasia tiene para el cirujano.

PMID- 30226490
TI  - [Tratamiento quirurgico de la escoliosis idiopatica del adolescente. Resultados
      en el Instituto Nacional de Rehabilitacion de Mexico. Seguimiento minimo de 24
      meses].
AB  - Antecedentes: La escoliosis idiopatica del adolescente se define como una
      deformidad tridimensional de la columna vertebral que se presenta entre los 10 y
      los 18 anos, y que se manifiesta con una curvatura vertebral en el plano coronal
      mayor de 10 degrees . Esta deformidad afecta al 2-3% de la poblacion general,
      pero solo el 10% del total requerira en algun momento tratamiento quirurgico. El
      metodo de eleccion para el manejo es el uso de tornillos transpediculares y
      barras desrotadoras. Objetivo: Realizar un analisis descriptivo de los pacientes
      que recibieron manejo quirurgico en nuestro instituto con tornillos
      transpediculares y barras. Metodo: Se trata de un estudio observacional,
      retrospectivo, analitico, abierto, de muestreo no probabilistico, en el que se
      incluyeron los pacientes tratados con manejo quirurgico entre 2012 y 2013. Las
      deformidades se estratificaron de acuerdo con la clasificacion de Lenke. El
      angulo de correccion de la deformidad, los niveles instrumentados, el sangrado
      transquirurgico y la presencia de complicaciones fueron las variables analizadas.
      Resultados: La mayoria de los pacientes presentaron curvas Lenke IBN, Nash Moe
      III, Cobb un promedio de 59.4 degrees  y cifosis de 47.8. En promedio se siguio a
      los pacientes por 35.84 meses, detectando un aumento de la curvatura coronal de
      2.28 degrees  y un aumento de la curvatura sagital de 2.8 degrees . Conclusion:
      Al comparar estos resultados y la literatura mundial se concluyo que el
      tratamiento de la escoliosis idiopatica del adolescente es un metodo seguro y
      reproducible que ofrece una mayor ventaja biomecanica y biologica sobre el uso de
      instrumentacion mixta utilizada anteriormente. Background: Adolescent's
      idiopathic scoliosis is defined as a three-dimensional deformity of the spine,
      which occurs between 10 and 18-year-old, has a spinal curvature >10 degrees  in
      the coronal plane. This deformity affects 2-3% of the general population,
      however, only 10% of the total will require surgery at some point. The method of
      choice for management is the use of pedicle screws and rods derotational.
      Objective: To perform a descriptive analysis of patients who received surgical
      treatment in our institute with pedicle screws and rods. Methods: This is an
      observational, retrospective, analytical, open study, non-probability sampling,
      in which patients requiring surgical treatment at our institute between 2012 and
      2013 were included, the deformities were stratified according to the
      classification of Lenke. The angle of deformity correction, instrumented levels,
      amount of bleeding, presence of complications were the variables analyzed.
      Results: Lenke classifying mostly IBN, Moe Nash III, an average of 59.4 degrees 
      Cobb and kyphosis of 47.8. On average it was followed patients for 35.84 months,
      detecting an increase 2.28 degrees  coronal curvature and sagittal curvature
      increase of 2.8 degrees . Conclusion: Comparing these results and world
      literature concluded that the treatment of adolescent's idiopathic scoliosis is a
      safe and reproducible method that provides greater biomechanical and biological
      advantage over the use of mixed instrumentation used previously.

PMID- 30226491
TI  - [Sindrome de Fitz-Hugh-Curtis en un paciente varon anciano. Caso y revision de la
      literatura].
AB  - El sindrome de Fitz-Hugh-Curtis (FHCS) es la inflamacion de la capsula hepatica
      sin afectacion del parenquima asociada a una enfermedad pelvica inflamatoria. Hay
      muy pocos casos descritos en varones. El sintoma caracteristico es el dolor
      abdominal en el cuadrante superior derecho, que hace que se confunda el cuadro
      con una enfermedad de la via biliar. Son caracteristicas las adherencias fuertes
      entre el diafragma y el higado en forma de "cuerda de violin". Presentamos el
      caso de un varon de 81 anos que se somete a una colecistectomia laparoscopica por
      pancreatitis de repeticion. Durante la cirugia se encuentran las caracteristicas
      adherencias en "cuerda de violin", que se seccionan. El paciente da positivo para
      anticuerpos contra Chlamydia trachomatis. Hay nueve casos descritos en la
      literatura de FHCS en varones. Este sindrome se confunde muchas veces con
      patologia infecciosa biliar, lo que nos obliga a someter al paciente a una
      cirugia para realizar el diagnostico cuando se encuentran las caracteristicas
      adherencias. Si sospechamos la enfermedad mediante las pruebas complementarias,
      podemos intentar tratarla con antibioticos.

PMID- 30226492
TI  - [Asociacion de la composicion corporal total con la fuerza del tronco, el dolor y
      la discapacidad en pacientes con espondiloartrosis lumbar].
AB  - Introduccion: Las alteraciones en la composicion corporal total podrian influir
      sobre la fuerza, el dolor y la discapacidad en pacientes con espondiloartrosis
      lumbar. Objetivo: Analizar la asociacion de la composicion corporal total con la
      fuerza muscular del tronco, el dolor y la discapacidad en pacientes con
      espondiloartrosis lumbar. Metodo: Estudio piloto en mayores de 50 anos con dolor
      cronico de espalda baja y espondiloartrosis lumbar. Se excluyeron pacientes con
      diabetes mellitus, depresion, ansiedad, artropatias inflamatorias, fracturas
      vertebrales, escoliosis, cirugias de columna, cardiopatias, hipertension
      arterial, radiculopatia o claudicacion neurogenica. Se recolectaron datos sobre
      tiempo de evolucion, composicion corporal (masa grasa y muscular total), fuerza
      del tronco (isocinesia), dolor (escala numerica verbal) y discapacidad (Roland
      Morris). Analisis estadistico con U de Mann-Whitney y correlaciones de Spearman.
      Resultados: 27 pacientes (18 mujeres y 9 hombres) con edad de 58.59 +/- 6.98
      anos. La masa muscular total se asocio con el dolor (rho: -0.63, p = 0.001) y con
      la fuerza del tronco (flexores rho: -0.42, p = 0.02; extensores rho: -0.50, p =
      0.007), sin correlacion con la discapacidad. No se encontro correlacion de la
      masa grasa con ninguna de las variables. Conclusion: La disminucion de la masa
      muscular se asocia con el dolor, pero no con la discapacidad, en pacientes con
      espondiloartrosis lumbar. Background: Variations in body composition among
      patients with lumbar osteoarthritis may influence pain and disability and muscle
      strength. Objective: To analyze the relationship between body composition with
      pain, disability and muscle strength, in patients with lumbar osteoarthritis.
      Methods: Pilot study in patients older than 50 years of age, with chronic low
      back pain and lumbar osteoarthritis, who agreed to participate through informed
      consent. We excluded patients with diabetes mellitus, depression, anxiety,
      inflammatory arthropathies, vertebral fractures, idiopathic scoliosis, spinal
      surgery, heart disease or hypertension, radiculopathy or neurogenic claudication.
      Data on evolution time, body composition (total body fat and muscle mass), trunk
      strength, pain (numerical rating scale), and disability (Roland Morris
      questionnaire) were collected. Mann-Whitney U-test and Spearman correlations were
      performed. Results: 27 patients (18 women and 9 men) aged 58.59 +/- 6.98 years.
      Negative correlations between muscle mass with pain (rho: -0.63, p = 0.001) and
      strength (flexors rho: -0.42, p = 0.02; extensors rho: -0.50, p = 0.007) were
      found, without correlation with disability. No correlations of fat mass with pain
      or disability were found. Conclusion: Decreased of muscle mass were associated
      with higher pain scores without influencing the disability in patients with
      lumbar osteoarthritis..

PMID- 30226493
TI  - [Diverticulo de Meckel con tejido pancreatico ectopico en un nino de 12 anos con
      invaginacion intestinal. Reporte de caso y revision de la literatura].
AB  - Introduccion: El diverticulo de Meckel es un remanente del conducto
      onfalomesenterico y su prevalencia es del 2%. Caso clinico: Nino de 12 anos con
      dolor abdominal, acompanado de evacuaciones mucosanguinolentas y hematemesis, con
      masa en cuadrante inferior derecho. En la laparotomia quirurgica se encontro
      invaginacion, y se realizo desinvaginacion y reseccion del diverticulo de Meckel.
      Conclusion: La asociacion de diverticulo de Meckel con tejido pancreatico
      heterotopico en ninos es poco frecuente. Clinicamente, su principal manifestacion
      es la invaginacion intestinal en la literatura revisada, y el ultrasonido
      constituye el mejor estudio para el diagnostico de invaginacion intestinal, no
      asi para el diverticulo de Meckel o el tejido pancreatico heterotopico, en los
      que la tomografia seria una opcion. Introduction: Meckel's diverticulum is a
      remnant of the omphalomesenteric duct and its prevalence is 2%. Clinical case: A
      12-year-old male with abdominal pain, accompanied by muco-sanguineous evacuations
      and hematemesis, with right lower quadrant mass. In the laparotomy, invasion was
      found; intussusception reduction and resection of the Meckel's diverticulum was
      performed. Conclusion: The association of Meckel's diverticulum with heterotopic
      pancreatic tissue in children is rare, its main manifestation is intussusception
      and ultrasound is an option for diagnosis.

PMID- 30226494
TI  - [Seguridad y eficacia del modelo de atencion fast-track vs. atencion convencional
      en apendicitis no complicada del paciente pediatrico].
AB  - Objetivo: Comparar la seguridad y la eficacia de la atencion fast-track vs.
      atencion convencional en apendicitis no complicada en un hospital pediatrico.
      Metodo: Ensayo clinico controlado, aleatorizado, con dos grupos de 30 pacientes
      cada uno: A) fast-track, apendicitis no complicada que cumplieron el programa; y
      B) atencion convencional, apendicitis no complicada con atencion habitual.
      Variables de seguridad y eficacia: proporcion de complicaciones y tiempo de
      estancia hospitalaria. Resultados: Se incluyeron 60 pacientes, sin diferencia
      entre grupos: sexo masculino (53 vs. 60%), edad (8 +/- 3 vs. 8 +/- 2 anos),
      tiempo de evolucion (23 +/- 21 vs. 24 +/- 20 horas), tiempo desde ingreso a
      urgencias hasta inicio de cirugia (6 +/- 4 vs. 8 +/- 6 horas), y tipo de
      apendicitis edematosa (27 vs. 24%) o supurada (73 vs. 76%). La estancia
      hospitalaria promedio del grupo fast-track fue de 13 +/- 5 vs. 72 +/- 40 horas
      del grupo de atencion convencional (p = 0.001). Hubo complicaciones en el 3 y el
      6%, respectivamente (p = 1.0). La estancia hospitalaria disminuyo 2.45 dias por
      paciente con el protocolo fast-track, lo que representa un ahorro de $ 6,731
      pesos/dia/paciente/hospitalizacion (US$ 373), sin un aumento de las
      complicaciones. Conclusion: El protocolo fast-track en los ninos con apendicitis
      no complicada es seguro y efectivo en un hospital universitario. El programa fast
      track aporto beneficios clinicos y economicos, ahorrando en total $ 403,860 en
      los 30 pacientes. Objective: To compare safety and efficacy of fast-track program
      vs. conventional attention in non-complicated appendicitis attending a pediatric
      university hospital. Method: Randomized clinical trial, comparing two groups with
      30 patients each: (A) fast-track group, appendicitis agreeing the treatment
      protocol; and (B) conventional attention group, appendicitis following habitual
      surgical care. The efficacy and safety measures were length of hospital stay and
      proportion of complications. Results: We included 60 patients, there were no
      significant difference between groups with regard: male gender (53 vs. 60%), age
      (8 +/- 3 vs. 8 +/- 2 years-old), time of evolution (23 +/- 21 vs. 24 +/- 20 h),
      time since admittance to emergency and beginning of surgery (6 +/- 4 vs. 8 +/- 6
      h), and type of appendicitis edematous (27 vs. 24%) or suppurate (73 vs. 76%).
      Mean length of hospital stay in fast-track group was 13 +/- 5 vs. 72 +/- 40 h in
      conventional attention (p = 0.001). The complications were 3 and 6%, respectively
      (p = 1.0). Fast-track program diminished length of hospital stay in 2.45 days per
      patient, representing a mean cost saving of 6,731 Mexican pesos per day, per
      patient hospitalized (US$ 373), without increased complications. Conclusion: Fast
      track program in children with non-complicated appendicitis is safe and effective
      in pediatric university hospital; there was cost-minimization without
      carelessness of safety. This program support clinical and economic benefits, a
      total saving of 403,860 Mexican pesos for the 30 patients in the fast-track
      group.

PMID- 30226495
TI  - [Comparacion entre ligadura con lazo hemostatico y engrapadora mecanica lineal
      para el cierre de base apendicular].
AB  - Introduccion: En las ultimas decadas es creciente el abordaje por minima invasion
      de patologias abdominales debido a sus beneficios evidentes. El cuadro
      apendicular es la principal emergencia quirurgica, con diferentes metodos del
      cierre de la base apendicular. En este articulo comparamos dicho cierre con
      engrapadora lineal o ligadura con lazo hemostatico, para analizar la frecuencia
      de complicaciones como absceso, dehiscencia y seroma. Metodo: Se realizo un
      estudio prospectivo, observacional y descriptivo, con un total de 703
      procedimientos, empleando en 567 pacientes ligadura con lazo hemostatico y en 136
      engrapadora lineal, operados por los mismos cirujano y equipo quirurgico, con
      curva de aprendizaje concluida. Resultados: Las complicaciones referidas en el
      presente estudio son absceso (n = 5), dehiscencia (n = 3) y seroma (n = 3). De
      acuerdo con las fases de la patologia apendicular: fase 1 o apendice congestivo,
      no presentaron complicaciones; fase 2 o supurativo, se reporto un caso de
      dehiscencia de herida quirurgica con el uso de ligadura con lazo hemostatico;
      fase 3 o necrotico, se reporto un caso de seroma en un paciente tratado con
      ligadura con lazo hemostatico; y fase 4 o perforado, se encuentra diferencia
      significativa en el caso de abscesos, reportando cinco con el uso de ligadura con
      lazo hemostatico y ninguno con engrapadora lineal. Conclusiones: En nuestro
      estudio no existe diferencia estadisticamente significativa entre el uso de
      engrapadora lineal o ligadura con lazo hemostatico en las fases apendiculares 1
      3; en la fase 4 es de utilidad significativa el uso de engrapadora lineal ante la
      incidencia de abscesos. Introduction: In the last decades, the approach by
      minimally invasive surgery of abdominal pathologies is growing due to its evident
      benefits; the appendicular cases being the main surgical emergency, with
      different methods of closing the appendicular base. In this article, we compared
      the appendicular base closure with linear stapler and endoloop, to analyze the
      frequency of complications such as abscess, dehiscence and seroma. Method: A
      prospective, observational and descriptive study was conducted, with a total of
      703 procedures, using 567 endoloop patients and 136 linear stapler, operated by
      the same surgeon and surgical team, with a completed learning curve. Results: The
      complications referred in the present study were patients with abscess (n = 5),
      dehiscence (n = 3) and seroma (n = 3). According to the phases of the appendiceal
      pathology: phase 1 or congestive appendix did not present complications; phase 2
      or suppurative was reported one case of surgical wound dehiscence in the use of
      endoloop; in phase 3 or necrotic, one case of seroma was reported in a patient
      treated with endoloop; while in phase 4 or perforated there is a significant
      difference in the case of abscesses, reporting five in the use of endoloop and
      none in the case of a linear stapler. Conclusions: In our study there is no
      statistically significant difference between the use of linear stapler or
      endoloop in the early appendicular phases; being of significant utility in Phase
      4 the use of linear stapler for the incidence of abscesses.

PMID- 30226496
TI  - [Indice de Mannheim y mortalidad en sepsis abdominal].
AB  - Introduccion: La sepsis abdominal representa la respuesta inflamatoria peritoneal
      ante la invasion microbiana, con una mortalidad del 17%. El indice de peritonitis
      de Mannheim es una herramienta clinica y un predictor de mortalidad, con alta
      sensibilidad y especificidad. Objetivo: Determinar si existe correlacion entre el
      puntaje obtenido mediante el indice de peritonitis de Mannheim y la mortalidad.
      Metodo: Estudio retrospectivo, observacional, transversal, durante el periodo
      entre julio de 2013 y enero de 2014, en pacientes con diagnostico de sepsis
      abdominal, en el Hospital General de Mexico Dr. Eduardo Liceaga. Resultados: Se
      incluyeron 177 casos, 85 de sexo femenino y 92 de sexo masculino. La edad media
      fue de 43 anos. El organo causante de la sepsis abdominal mas frecuente fue el
      apendice. Fallecieron 18 pacientes (10.2%). Se dividieron los casos, de acuerdo
      con el indice de Mannheim, en leves (< 25 puntos) y graves (> 26 puntos). De 27
      pacientes graves, fallecieron 8 (29.6%), mientras que de los 150 leves
      fallecieron 10 (6.7%) (odds ratio: 5.895; intervalo de confianza del 95%: 2.071
      16.77; p < 0,05). Conclusion: El indice de Mannheim es un buen predictor de
      mortalidad para los pacientes con sepsis abdominal. El punto de corte optimo es
      20. Background: Abdominal sepsis represents the host's peritoneal inflammatory
      response to microbial invasion, which may be mild or severe, depending on the
      degree of contamination of the peritoneal cavity; with a reported mortality of
      17%. The Mannheim peritonitis index is a clinical tool and a predictor of
      mortality in patients with peritonitis, with high sensitivity and specificity.
      Objective: To determine if there is a correlation between the score obtained by
      the Mannheim peritonitis index, and mortality, in patients with abdominal sepsis.
      Method: A retrospective, observational, cross-sectional study, during the period
      between July 2013 and January 2014, in patients diagnosed with abdominal sepsis,
      attended at the General Hospital of Mexico Dr. Eduardo Liceaga. Results: We
      included 177 cases, 85 of the female sex and 92 of the male sex. The average age
      was 43 years. The most common organ responsible for abdominal sepsis was the
      appendix. Mortality of 18 cases (10.2%). The cases were divided, according to the
      Mannheim index, in mild cases (< 25 points) and severe case (> 26 points). Of 27
      severe cases, 8 (29.6%) died, while of the 150 mild cases 10 (6.7%) died (odds
      ratio: 5.895; 95% confidence interval: 2.071-16.77; p < 0.05). Conclusions: The
      Mannheim scale is a good predictor of mortality for patients with abdominal
      sepsis. The optimal cut-off point is 20.

PMID- 30226497
TI  - [Riesgo de recurrencia y de nuevas neoplasias cutaneas malignas en sujetos
      mexicanos con carcinoma basocelular].
AB  - Introduccion: El carcinoma basocelular (CBC) es la neoplasia cutanea maligna mas
      comun. Objetivo: se investigo el riesgo de recurrencia y de nueva neoplasia
      cutanea maligna despues del tratamiento de CBC. Metodo: Estudio retrospectivo.
      Fueron identificados los pacientes con diagnostico histopatologico de CBC
      primario, de enero de 2007 a diciembre de 2009, y se revisaron los expedientes
      para investigar el numero de recurrencias, la localizacion, el tipo de
      tratamiento y la variante histopatologica, determinando nuevas neoplasias
      cutaneas malignas. El analisis incluyo estadistica descriptiva e inferencial,
      considerando significativa una p < 0.05. Resultados: Se incluyeron 397 pacientes,
      con un seguimiento promedio de 4 +/- 1.5 anos. La recurrencia se presento en el
      4% y se relaciono con un mayor tiempo de evolucion (36 vs. 32 meses; p = 0.04) y
      haber sido tratado mediante tecnicas destructivas (electrofulguracion,
      criocirugia o imiquimod; 31 vs. 4%; p = 0.0004). No hubo relacion con la
      localizacion ni con la variante histopatologica. El riesgo de desarrollar una
      nueva neoplasia maligna fue del 25%, y de ellas el 66% correspondio a un nuevo
      CBC y el 30% a carcinoma espinocelular. Conclusiones: Es importante el
      seguimiento de los pacientes con CBC para identificar tanto las recurrencias como
      las nuevas neoplasias malignas, independientemente de la localizacion y de la
      variante histopatologica del primario. El tratamiento con tecnicas quirurgicas
      condiciona una menor recaida que las tecnicas destructivas. Introduction: Basal
      cell carcinoma (BCC) is the most common skin malignant neoplasm. Objective.:
      Investigate the risk of recurrence and of new skin malignant neoplasms, after
      treatment of BCC. Method: Retrospective study. We examined the files of patients
      with histopathological diagnosis of primary BCC, between January 2007 and
      December 2009, and we investigate number of recurrences and their relationship
      with localization, treatment type, and histopathological variant, and the number
      of new skin malignant neoplasms. For analysis, we employed descriptive and
      inferential statistics; p < 0.05 was considered significant. Results: A total of
      397 patients, with an average follow-up of 4 +/- 1.5 years. Recurrences presented
      in 4%. Recurrences were related with longer time of evolution (36 vs. 32 months;
      p = 0.04) and treatment with destructive techniques (electrofulguration,
      cryosurgery or imiquimod; 31 vs. 4%; p < 0.001). There was no relationship with
      localization, or the histopathological variant. The risk of developing a new
      malignant neoplasm was 25%; 66% corresponded to a new BCC and 30% to squamous
      cell carcinoma. Conclusions: Follow-up of patients with BCC should be conducted
      independently of their localization and histopathological variant, especially in
      patients with greater evolution time, principally with surgical techniques.

PMID- 30226498
TI  - [Variacion estacional de las amputaciones en un hospital universitario de
      Monterrey, Mexico (2009-2012)].
AB  - Antecedentes: Una de las principales complicaciones de la diabetes mellitus es la
      amputacion de alguna extremidad. En todo el mundo, la prevalencia de amputaciones
      asociadas a la diabetes es muy variada y tiene un impacto considerable en la
      calidad de vida del paciente. Objetivo: Analizar la frecuencia de las
      amputaciones en el Hospital Universitario Dr. Jose E. Gonzalez y evaluar si se
      presenta un patron estacional. Metodo: Se realizo un estudio retrospectivo de
      2009 a 2012, en el que se revisaron los expedientes de pacientes diabeticos que
      se sometieron a amputacion. La estacionalidad se analizo con la bondad de ajuste
      de ji al cuadrado. Resultados: Se analizaron 456 amputaciones. Los resultados
      muestran que febrero es el mes que presenta la mayor frecuencia de amputaciones.
      La estacion anual con mayor numero de amputaciones fue el invierno. Conclusiones:
      Las amputaciones en pacientes diabeticos del area metropolitana de Monterrey
      presentan un patron estacional, siendo los meses de invierno los de mayor
      frecuencia. Background: The amputation of an extremity is a main complication of
      Diabetes mellitus. Worldwide the prevalence of amputations associated with
      diabetes mellitus is variable and had a considerable impact in the quality of
      life. Objective: Analyze the frequency of amputations in the University Hospital,
      Dr Jose E Gonzalez and evaluate if a seasonal pattern is present. Method: A
      retrospective analysis from 2009 to 2012 was carried out. Clinical files of
      diabetic patients undergoing to amputation were studied. The seasonality was
      evaluated with a chi square goodness of fit. Results: A total of 456 amputations
      were studied. Results shown that February was the month with highest frequency of
      amputations while winter was the annual season with highest frequency of
      amputations. Conclusions: Amputations of diabetic patients from Metropolitan
      Monterrey Mexico show a seasonal pattern being the winter months those that
      present highest frequency.

PMID- 30226499
TI  - [La educacion multimedia como apoyo en el manejo de pacientes con diabetes tipo
      2. Estudio cuasi experimental].
AB  - Objetivo: Evaluar la eficacia de la educacion a traves de un sistema de
      informacion multimedia en el control del paciente con diabetes tipo 2. Metodo:
      Ensayo clinico abierto aleatorizado. El grupo de intervencion fue instruido para
      consultar una herramienta educativa multimedia en la sala de espera de los
      consultorios, misma que fue disenada de acuerdo a las caracteristicas de la
      poblacion y centrada en automonitoreo de indicadores, informacion sobre diabetes
      tipo 2 y nutricion. Se midieron en sangre venosa las concentraciones de glucosa,
      hemoglobina glucosilada (HbA1c), trigliceridos, colesterol total, colesterol
      ligado a lipoproteinas de alta densidad (HDL-c) y colesterol ligado a
      lipoproteinas de baja densidad. Con la t de Student pareada se evaluo el efecto
      de la intervencion. Resultados: Se incluyeron 2334 pacientes, 958 en el grupo de
      intervencion y 1376 en el grupo control. Se observo en el grupo de intervencion
      un incremento del HDL-c (de 40.45 a 47.40 mg/dl; p = 0.001) y una disminucion de
      los trigliceridos (de 227.78 a 210.38 mg/dl; p = 0.001). En el grupo control
      disminuyeron los trigliceridos (de 232.64 a 210.84 mg/dl; p = 0.016). En ambos
      grupos se incremento de forma significativa el colesterol total. No se observaron
      cambios en los valores de glucosa y HbA1c posterior a la intervencion.
      Conclusion: La implementacion de un sistema de informacion multimedia mejora el
      HDL-c y los trigliceridos del paciente con diabetes. Se requiere un reforzamiento
      continuo de la intervencion educativa por parte del profesional de la salud para
      incidir en el control glucemico y otros indicadores del control metabolico.
      Objective: To evaluate the efficacy of education through a multimedia information
      system, in controlling patients with type 2 diabetes. Methods: Randomized open
      clinical trial. The intervention group was trained to consult an educative
      multimedia tool in the waiting room, which was developed according to the
      population characteristics and centered on monitoring indicators, information on
      type 2 diabetes and nutrition. Venous blood concentrations of glucose, glycated
      hemoglobin (HbA1c), triglycerides, total cholesterol, high-density lipoprotein
      cholesterol, and low-density lipoprotein cholesterol were measured. Paired t
      Student was used to assess the effect of the intervention. Results: 2,334
      patients were included, 958 in the intervention group and 1,376 in the control
      group. In the intervention group, an increase in HDL-c values was observed (from
      40.45 to 47.40 mg/dL; p=0.001) as well as a descent on triglycerides values (from
      227.78 to 210.38 mg/dL; p=0.001). There was a reduction on triglycerides levels
      in the control group (from 232.64 to 210.84 mg/dL; p=0.016). There was a
      significative increase in total cholesterol values in both groups. There were no
      changes in the mean values of glucose and HbA1c after the intervention.
      Conclusion: Implementation of a multimedia information system improves HDL-c and
      triglycerides in patients with diabetes. There is a need for a continuous
      reinforcement of the educative intervention by health professionals to improve
      glycemic and other indicators in metabolic control.

PMID- 30226500
TI  - In situ analytical characterization and chemical imaging of tablet coatings using
      laser induced breakdown spectroscopy (LIBS).
AB  - Laser induced breakdown spectroscopy (LIBS) has emerged as an innovative tool for
      quantitative and qualitative elemental analysis in pharmaceutical research.
      Herein, the potential use of LIBS for rapid characterization of tablet coatings
      is illustrated, including the investigation of coating thickness, coating
      uniformity and localized coating contamination. The laser shot number required
      for penetrating the coating correlates well with coating thickness determined
      from traditional scanning electron microscopy measurements. Each laser shot
      represents a 2.58 MUm coating thickness. The inter-tablet coating uniformity was
      directly visualized using LIBS-based 3D chemical imaging, and the intra-tablet
      coating uniformity was quantitatively investigated. To our knowledge, this is the
      first report of 3D LIBS-based chemical imaging being utilized for quantitative
      analysis of pharmaceutical tablet coatings. In addition to elemental information,
      the accurate location of contaminants on the tablet coating was rapidly
      identified using 2D imaging. These results pave the way for LIBS to be a valuable
      technique for the analysis of pharmaceutical tablet coatings.

PMID- 30226501
TI  - Microbiosensor fabrication by polydimethylsiloxane stamping for combined sensing
      of glucose and choline.
AB  - High performance microprobes for combined sensing of glucose and choline were
      fabricated using microcontact printing (MUCP) to transfer choline oxidase (ChOx)
      and glucose oxidase (GOx) onto targeted sites on microelectrode arrays (MEAs).
      Most electroenzymatic sensing sites on MEAs for neuroscience applications are
      created by manual enzyme deposition, which becomes problematic when the array
      feature size is less than or equal to ~100 MUm. The MUCP process used here relies
      on use of soft lithography to create features on a polydimethylsiloxane (PDMS)
      microstamp that correspond to the dimensions and array locations of targeted,
      microscale sites on a MEA. Precise alignment of the stamp with the MEA is also
      required to transfer enzyme only onto the specified microelectrode(s). The dual
      sensor fabrication process began with polyphenylenediamine (PPD)
      electrodeposition on all Pt microelectrodes to block common interferents (e.g.,
      ascorbic acid and dopamine) found in brain extracellular fluid. Next, a chitosan
      film was electrodeposited to serve as an adhesive layer. The two enzymes, ChOx
      and GOx, were transferred onto different microelectrodes of 2 * 2 arrays using
      two different PDMS stamps and a microscope for stamp alignment. Using constant
      potential amperometry, the combined sensing microprobe was confirmed to have high
      sensitivity for choline and glucose (286 and 117 MUA mM cm-2, respectively)
      accompanied by low detection limits (1 and 3 MUM, respectively) and rapid
      response times (<=2 s). This work demonstrates the use of MUCP for facile
      creation of multianalyte sensing microprobes by targeted deposition of enzymes
      onto preselected sites of a microelectrode array.

PMID- 30226502
TI  - DNA methylation detection: recent developments in bisulfite free electrochemical
      and optical approaches.
AB  - DNA methylation is one of the significant epigenetic modifications involved in
      mammalian development as well as in the initiation and progression of various
      diseases like cancer. Over the past few decades, an enormous amount of research
      has been carried out for the quantification of DNA methylation in the mammalian
      genome. Earlier, most of these methodologies used bisulfite treatment. However,
      the low conversion, false reading, longer assay time and complex chemical
      reaction are the common limitations of this method that hinder their application
      in routine clinical screening. Thus, as an alternative to bisulfite conversion
      based DNA methylation detection, numerous bisulfite-free methods have been
      proposed. In this regard, electrochemical biosensors have gained much attention
      in recent years for being highly sensitive yet cost-effective, portable, and
      simple to operate. On the other hand, biosensors with optical readouts enable
      direct real time detection of biological molecules and are easily adaptable to
      multiplexing. Incorporation of electrochemical and optical readouts into
      bisulfite free DNA methylation analysis is paving the way for the translation of
      this important biomarker into standard patient care. In this review, we provide a
      critical overview of recent advances in the development of electrochemical and
      optical readout based bisulfite free DNA methylation assays.

PMID- 30226503
TI  - Multiple reaction monitoring (MRM)-profiling with biomarker identification by LC
      QTOF to characterize coronary artery disease.
AB  - Metabolite profiling by mass spectrometry (MS) is an area of interest for disease
      diagnostics, biomarker discovery, and therapeutic evaluation. A recently
      developed approach, multiple reaction monitoring (MRM)-profiling, searches for
      metabolites with precursor (Prec) and neutral loss (NL) scans in a representative
      sample and creates a list of ion transitions. These are then used in an MRM
      method for fast screening of individual samples and discrimination between
      healthy and diseased. A large variety of functional groups are considered and all
      signals discovered are recorded in the individual samples, making this a largely
      unsupervised method. MRM-profiling is described here and then demonstrated with
      data for over 900 human plasma coronary artery disease (CAD) samples.
      Representative pooled samples for each condition were interrogated using a
      library of over a hundred Prec and NL scans on a triple quadrupole MS. The data
      from the Prec and NL experiments were converted into ion transitions, initially
      some 1266 transitions. Each ion transition was examined in the individual samples
      on a time scale of milliseconds per transition, which allows for rapid screening
      of large sample sets (<5 days for 1000 samples). Use of univariate and
      multivariate statistics allowed classification of the sample set with high
      accuracy. The metabolite profiles classified the CAD female, CAD male, and
      peripheral artery disease (PAD) samples relative to controls with an accuracy of
      90%, 78%, and 85%, respectively. The compounds responsible for informative ion
      transitions were identified by chromatography and high resolution MS; some have
      been previously reported and found to be associated with coronary artery disease
      metabolism, indicating that the methodology generates a meaningful metabolite
      profile while being faster than traditional methodologies.

PMID- 30226504
TI  - Fabrication and application of BN nanoparticles, nanosheets and their
      nanohybrids.
AB  - Smart implementation of novel advanced nanomaterials is the key for the solution
      of many complex problems of modern science. In recent years, there has been a
      great interest in the synthesis and application of boron nitride (BN) nanotubes
      because of their unique physical, chemical, and mechanical properties. By
      contrast, the synthesis, characterization and exploration of other morphological
      types of BN nanostructure - BN nanoparticles and BN nanosheets - have received
      less attention. However, the detailed investigations on advantages of every
      morphological BN type for specific applications have only recently been started.
      One of the promising directions is the utilization of BN-based nanohybrids. This
      review is dedicated to the in-depth analysis of recently published works on the
      fabrication and application of BN nanoparticles, nanosheets, and their
      nanohybrids. It covers a variety of developed synthetic methods toward
      fabrication of such nanostructures, and their specific application potentials in
      catalysis, drug delivery, tribology and structural materials. Finally, the review
      focuses on the theoretical aspects of this quickly emerging field.

PMID- 30226505
TI  - Natural reaction channels in H + CHD3 -> H2 + CD3.
AB  - Natural reaction channels are defined by the singular value decomposition of the
      S-matrix and can be interpreted as pathways through the transition state of the
      reaction. Here, the reaction probabilities and asymptotic state distributions
      associated with the natural reaction channels of the H + CHD3 -> H2 + CD3
      reactions are presented. The analysis is based on accurate quantum dynamics data
      obtained by full-dimensional (multi-layer) multi-configurational time-dependent
      Hartree (MCTDH) calculations using the quantum transition state framework and a
      high-level ab initio potential energy surface. The reaction starting from several
      different initial ro-vibrational states is investigated. The results provide
      interesting insights into symmetry-related differences between the mode-selective
      chemistry of CH4 and CHD3. The presence of localized vibrational modes in CHD3 is
      found to limit the loss of memory effect seen in the H + CH4 -> H2 + CH3 reaction
      and to give rise to spectator behavior of the selected modes. Furthermore, the
      recently found reactivity borrowing effect, which results from a Fermi resonance
      type state mixing of the triple umbrella excited and single C-H-stretch excited
      states of CHD3, is investigated. Here, the natural reaction channel analysis
      provides detailed information on the resonant energy transfer in the entrance
      channel of the reaction and the correlation between the asymptotic states of the
      reactants and the vibrational states of the activated complex.

PMID- 30226506
TI  - Artificial water channels: inspiration, progress, and challenges.
AB  - This article is based on the concluding remarks made in the Faraday Discussion
      Meeting on Artificial Water Channels.

PMID- 30226507
TI  - Effects of symmetry breaking on the translation-rotation eigenstates of H2, HF,
      and H2O inside the fullerene C60.
AB  - Splittings of the translation-rotation (TR) eigenstates of the solid light
      molecule endofullerenes M@C60 (M = H2, H2O, HF) attributed to the symmetry
      breaking have been observed in the infrared (IR) and inelastic neutron scattering
      spectra of these species in the past couple of years. In a recent paper [Felker
      et al., Phys. Chem. Chem. Phys., 2017, 19, 31274], we established that the
      electrostatic, quadrupolar interaction between the guest molecule M and the
      twelve nearest-neighbor C60 cages of the solid is the main source of the symmetry
      breaking. The splittings of the three-fold degenerate ground states of the
      endohedral ortho-H2, ortho-H2O and the j = 1 level of HF calculated using this
      model were found to be in excellent agreement with the experimental results.
      Utilizing the same electrostatic model, this theoretical study investigates the
      effects of the symmetry breaking on the excited TR eigenstates of the three
      species, and how they manifest in their simulated low-temperature (5-6 K) near-IR
      (NIR) and far-IR (FIR) spectra. The TR eigenstates are calculated variationally
      for both the major P and minor H crystal orientations. For the H orientation, the
      calculated splittings of all of the TR levels of these species are less than 0.1
      cm-1. For the dominant P orientation, the splittings vary strongly depending on
      the character of the excitations involved. In all of the species, the splittings
      of the higher rotationally excited levels are comparable in magnitude to those
      for the j = 1 levels. For the levels corresponding to purely translational
      excitations, the calculated splittings are about an order of magnitude smaller
      than those of the purely rotational eigenstates. Based on the computed TR
      eigenstates, the low-temperature NIR (for M = H2) and FIR (for M = HF and H2O)
      spectra are simulated for both the P and H orientations, and also combined as
      their weighted sum (0.15H + 0.85P). The weighted sum spectra computed for M = H2
      and HF match quantitatively the corresponding measured spectra, while for M =
      H2O, the weighted sum FIR spectrum predicts features that can potentially be
      observed experimentally.

PMID- 30226508
TI  - Oxygen plasmas: a sharp chisel and handy trowel for nanofabrication.
AB  - Although extremely chemically reactive, oxygen plasmas feature certain properties
      that make them attractive not only for material removal via etching and
      sputtering, but also for driving and sustaining nucleation and growth of various
      nanostructures in plasma bulk and on plasma-exposed surfaces. In this minireview,
      a number of representative examples is used to demonstrate key mechanisms and
      unique capabilities of oxygen plasmas and how these can be used in present-day
      nano-fabrication. In addition to modification and functionalisation processes
      typical for oxygen plasmas, their ability to catalyse the growth of complex
      nanoarchitectures is emphasized. Two types of technologies based on oxygen
      plasmas, namely surface treatment without a change in the size and shape of
      surface features, as well as direct growth of oxide structures, are used to
      better illustrate the capabilities of oxygen plasmas as a powerful process
      environment. Future applications and possible challenges for the use of oxygen
      plasmas in nanofabrication are discussed.

PMID- 30226509
TI  - Synthesis of macrocyclic precursors of the vioprolides.
AB  - The vioprolides are novel depsipeptides that have not been synthesized. However,
      they have been identified as important targets for synthesis because of their
      novel biological activities and challenging chemical structures. Following early
      work on the synthesis of a modified tetrapeptide that contained both the (E)
      dehydrobutyrine and thiazoline components of vioprolide D, problems were
      encountered in taking an (E)-dehydrobutyrine containing intermediate further into
      the synthesis. A second approach to vioprolides and analogues was therefore
      investigated in which (E)- and (Z)-dehydrobutyrines were to be introduced by
      selenoxide elimination very late in the synthesis. A convergent approach to
      advanced macrocyclic precursors of the vioprolides was then completed using a
      modified hexapeptide and a dipeptidyl glycerate. In this work, it was necessary
      to protect the 2-hydroxyl group of the glycerate as its acetate and not as its
      2,2,2-trichloroethoxycarbonate. Preliminary studies were carried out on the
      introduction of the required dehydrobutyrine and thiazoline components into
      advanced intermediates.

PMID- 30226510
TI  - Pseudocapacitive behavior of the Fe2O3 anode and its contribution to high
      reversible capacity in lithium ion batteries.
AB  - Pseudocapacitance, which is the storage of charge based on continuous and fast
      reversible redox reactions at the surface of electrode materials, is commonly
      observed for electrodes in lithium ion batteries, especially for transition metal
      oxide anodes. In this report, bare Fe2O3 of granular morphology (~30 nm in
      diameter) with high purity and decent crystallinity as well as recommendable
      electrochemical performances is fabricated hydrothermally and employed as the
      subject to clarify pseudocapacitive behavior in transition metal oxide anodes.
      Electrochemical technologies such as galvanostatic charging/discharging,
      differential capacity analysis (dQ/dV) and the power law relationship (i = anub),
      which can distinguish pseudocapacitive behaviors of an electrode reaction were
      employed to analyze the electrodes. Reversible capacities of ~120 mA h g-1 (0.117
      F cm-2) for Fe2O3 were found within particular electrochemical windows (2.3-3.0
      V, 0.3-0.8 V for discharging and 2.2-3.0 V, 0.3-1.3 V for charging). A new
      direction of optimizing the capacities, rate and cycling performances for lithium
      ion batteries is pointed out with connections between the pseudocapacitive
      behavior and morphologies of surfaces as well as structures of the electrodes.

PMID- 30226511
TI  - Length-dependent dual-mechanism-controlled failure modes in silver penta-twinned
      nanowires.
AB  - A series of molecular dynamics simulations on silver penta-twinned nanowires are
      performed to reveal the tensile failure mechanisms that are responsible for the
      different failure modes and morphologies of fracture surfaces observed in various
      experimental reports. The simulations show that a ductile-to-brittle transition
      in failure mode occurs with increasing length of the nanowires. Short nanowires
      have ductile-like plasticity with flat-like fracture surfaces, while long
      nanowires show brittle-like fractures with cone-like failure surfaces. These two
      seemingly counterintuitive scenarios can be attributed to two sets of mechanisms:
      (1) stable dislocation nucleation-controlled incipient plasticity followed by
      stable dislocation motion-mediated plasticity assisted by pores for short
      nanowires, (2) unstable dislocation nucleation-controlled incipient plasticity
      followed by rapid necking for long nanowires. These two sets of failure
      mechanisms are distinguished by fitted lines using phased strain data. We propose
      a general strategy to build a necking-based model for predicting the critical
      nanowire aspect ratio while distinguishing the fracture modes. A mechanism map of
      silver penta-twinned nanowire is constructed to delineate the predominant failure
      behaviours. Our findings reveal a correlation between the failure mode and the
      resulting morphology of the fracture surface and provide a paradigm for the
      design and engineering of mechanical properties of nanowires.

PMID- 30226512
TI  - Phosphonium hydrogels for controlled release of ionic cargo.
AB  - We describe the synthesis of three different phosphonium salts and their reaction
      with poly(ethylene glycol) dimethacrylate to create cationic hydrogels. The
      hydrogels were loaded with an anionic dye and an anionic anti-inflammatory drug
      through ionic interactions and compared with an analogous ammonium gel. The
      release rates of these anions depended on their structure and pKa values, as well
      as the pH and ionic strength of the release medium.

PMID- 30226513
TI  - Supramolecular recognition of a CWA simulant by metal-salen complexes: the first
      multi-topic approach.
AB  - Sensing of chemical warfare agents is today an important target, mainly due to
      the international scenario. Here a new approach, based on supramolecular multi
      topic recognition of dimethyl methylphosphonate, a simulant of chemical warfare
      agents, is reported. These receptors, based on metal-salen complexes, combine
      their abilities to establish Lewis acid-base interactions and hydrogen bonds and
      pave the way for the realization of a new class of supramolecular sensors for the
      non-covalent recognition of chemical warfare agent simulants.

PMID- 30226514
TI  - Observation of physisorption in a high-performance FET-type oxygen gas sensor
      operating at room temperature.
AB  - Oxygen (O2) sensors are needed for monitoring environment and human health. O2
      sensing at low temperature is required, but studies are lacking. Here we report,
      for the first time, that the performance of a field effect transistor (FET)-type
      O2 sensor operating at 25  degrees C was improved greatly by a physisorption
      sensing mechanism. The sensing material was platinum-doped indium oxide (Pt
      In2O3) nanoparticles formed by an inkjet printer. The FET-type sensor showed
      excellent repeatability under a physisorption mechanism and showed much better
      sensing performance than a resistor-type sensor fabricated on the same wafer at
      25  degrees C. The sensitivity of the sensor increased with increasing Pt
      concentration up to ~10% and decreased with further increasing Pt concentration.
      When the sensing temperature reached 140  degrees C, the sensing mechanism of the
      sensor changed from physisorption to chemisorption. Interestingly, the pulse pre
      bias before the read bias affected chemisorption but had no effect on
      physisorption.

PMID- 30226515
TI  - Engineered nanoceria cytoprotection in vivo: mitigation of reactive oxygen
      species and double-stranded DNA breakage due to radiation exposure.
AB  - Cerium oxide nanomaterials are known to absorb ionizing radiation energy, as well
      as to neutralize free radicals in solution, by undergoing redox changes. We,
      therefore, proposed that ceria nanoparticles could be used in biomedical
      applications as an injectable, radio-protectant material. In this study, we
      examine the effectiveness of engineered nanoparticles in protecting germ cells
      from the damaging effects of irradiation-induced cell death, in vivo. C57BL/6J
      male mice were used as a model and irradiation was localized to the scrotal
      region at 2.5, 5, and/or 10 Gy intensities. Ceria nanoparticles were introduced
      as 100 MUL injections at 100 nM and 100 MUM via tail vein injections, weekly, for
      one month. Following this, the animals were sacrificed and their organs (heart,
      brain, kidneys) were harvested. Tissues were fixed, sectioned, and stained for
      instances of cell death, DNA damage (TUNEL assay), and ROS (nitro-tyrosine
      evolution). Tissues from mice treated with ceria nanoparticles showed
      significantly less (~13% decrease; *P < 0.05) tissue damage (per
      immunohistochemistry) over controls at up to 5 Gy radiation. DNA damage and ROS
      also decrease substantially with ceria treatment, confirming ceria's capacity as
      an injectable, radio-protectant material. The study also highlights the ability
      of ceria nanoparticles to protect cells/tissues from both direct and indirect
      effects of ionizing radiation.

PMID- 30226516
TI  - Photoluminescence, radioluminescence and thermoluminescence properties of Eu3+
      doped cadmium tantalate phosphor.
AB  - For investigate spectroscopic properties, Eu3+ doped columbite type CdTa2O6
      phosphors were synthesized using the solid state reaction method. The synthesized
      ceramic phosphors were investigated by X-ray diffraction (XRD), scanning electron
      microscopy-energy dispersive spectroscopy (SEM-EDS), photoluminescence (PL),
      radioluminescence (RL) and thermoluminescence (TL) analyses. CdTa2O6:Eu3+
      phosphors exhibited emissions at 591.8 nm and 612.1 nm because of the
      characteristic band transitions of the Eu3+ ion. Phosphor emission increased with
      increasing Eu3+ ion dopant up to 1.5 mol%, and then decreased owing to
      concentration quenching. The decay times decreased with increasing Eu3+ dopant,
      while they were varied from 711 to 534 MUm. The scintillation emissions of Eu3+
      doped samples from the UV to near-IR spectral region were monitored by RL
      measurements. The high RL emission may be attributed to the good scintillation
      property of phosphor. TL glow curves were monitored for different Eu3+
      concentrations in the range of 50  degrees C to 400  degrees C at a heating rate
      of 2  degrees C s-1, after being irradiated under short-wave UV light (254 nm).

PMID- 30226517
TI  - Synthesis of nanosized SAPO-34 with the assistance of bifunctional amine and
      seeds.
AB  - Nanosized SAPO-34 with a tunable silica content (acidity) has been synthesized
      with the assistance of bifunctional amine 1-[2-(2-hydroxyethoxy)ethyl]piperazine
      (HEEP) or its analog 1-(2-hydroxyethyl)piperazine (HEP), in which the piperazinyl
      group acting as a co-template prompts the formation of the pure CHA phase, and
      the hydroxyl/ether groups help inhibit the crystal growth. The resultant
      nanocrystallines possess a large amount of Si(4Al) species, improve transport
      properties as confirmed by IGA, and thus exhibit enhanced MTO catalytic
      performance.

PMID- 30226518
TI  - Functionalised heterogeneous catalysts for sustainable biomass valorisation.
AB  - Efficient transformation of biomass to value-added chemicals and high-energy
      density fuels is pivotal for a more sustainable economy and carbon-neutral
      society. In this framework, developing potential cascade chemical processes using
      functionalised heterogeneous catalysts is essential because of their versatile
      roles towards viable biomass valorisation. Advances in materials science and
      catalysis have provided several innovative strategies for the design of new
      appealing catalytic materials with well-defined structures and special
      characteristics. Promising catalytic materials that have paved the way for
      exciting scientific breakthroughs in biomass upgrading are carbon materials,
      metal-organic frameworks, solid phase ionic liquids, and magnetic iron oxides.
      These fascinating catalysts offer unique possibilities to accommodate adequate
      amounts of acid-base and redox functional species, hence enabling various biomass
      conversion reactions in a one-pot way. This review therefore aims to provide a
      comprehensive account of the most significant advances in the development of
      functionalised heterogeneous catalysts for efficient biomass upgrading. In
      addition, this review highlights important progress ensued in tailoring the
      immobilisation of desirable functional groups on particular sites of the above
      listed materials, while critically discussing the role of consequent properties
      on cascade reactions as well as on other vital processes within the bio-refinery.
      Current challenges and future opportunities towards a rational design of novel
      functionalised heterogeneous catalysts for sustainable biomass valorisation are
      also emphasized.

PMID- 30226519
TI  - Crystal structure, luminescence properties, energy transfer, tunable occupation
      and thermal properties of a novel color-tunable phosphor NaBa1
      zSrzB9O15:xCe3+,yMn2.
AB  - A series of color-tunable NaBa1-zSrzB9O15:Ce3+,Mn2+ phosphors were synthesized by
      a high temperature solid state method. Luminescence property, energy transfer,
      thermal stability and cation substitution were investigated in detail. Due to
      energy transfer, NaBaB9O15:Ce3+,Mn2+ presents violet to green luminescence and
      manifest a broad excitation range from 200 to 350 nm. The energy transfer
      mechanism of Ce3+-Mn2+ is identified as a dipole-dipole interaction. NaBa1
      zSrzB9O15:Ce3+,Mn2+ displays both Ce3+ violet and Mn2+ green and orange emissions
      under ultraviolet excitation. It is observed that Sr2+ partial substitution for
      Ba2+ could adjust the ratio of Mn2+ emission intensity in different cation sites,
      which results from preferred sites' occupation with modification of the crystal
      structure. Furthermore, increase in temperature can enhance the energy transfer
      from Ce3+ to Mn2+, which enhances the Mn2+ emission intensity sharply. The highly
      thermal-sensitive property of NaBa1-zSrzB9O15:Ce3+,Mn2+ makes it feasible for its
      potential application in luminescent ratiometric thermometers with wide
      temperature range.

PMID- 30226520
TI  - Optimized single-layer MoS2 field-effect transistors by non-covalent
      functionalisation.
AB  - Field-effect transistors (FETs) with non-covalently functionalised molybdenum
      disulfide (MoS2) channels grown by chemical vapour deposition (CVD) on SiO2 are
      reported. The dangling-bond-free surface of MoS2 was functionalised with a
      perylene bisimide derivative to allow for the deposition of Al2O3 dielectric.
      This allowed the fabrication of top-gated, fully encapsulated MoS2 FETs.
      Furthermore, by the definition of vertical contacts on MoS2, devices, in which
      the channel area was never exposed to polymers, were fabricated. The MoS2 FETs
      showed some of the highest mobilities for transistors fabricated on SiO2 with
      Al2O3 as the top-gate dielectric reported so far. Thus, gate-stack engineering
      using innovative chemistry is a promising approach for the fabrication of
      reliable electronic devices based on 2D materials.

PMID- 30226521
TI  - In vitro effect of green tea and turmeric extracts on GLP-1 and CCK secretion:
      the effect of gastrointestinal digestion.
AB  - Plant extract activity can be modified by the digestion process. In order to
      assess the satiety effect of green tea and turmeric extracts, an in vitro
      gastrointestinal digestion process was performed and the STC-1 cell line was
      used. The enteroendocrine cell line was incubated (for 30, 60 and 120 minutes)
      with the digested and non-digested extracts measuring the secretion of
      cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) by enzyme-linked
      immunosorbent assay (ELISA). The release of satiety hormones by the STC-1 cells
      showed similar or higher results for plant extracts compared to the positive
      controls reported as satiatogenic (proteins and short chain fatty acids). For the
      non-digested samples, the largest amount of CCK and GLP-1 was found for turmeric,
      with 379 +/- 46 pg ml-1 (60 min) and 347 +/- 125 pg ml-1 (120 min) respectively.
      For the digested samples, the highest level of CCK was found for turmeric at 30
      minutes (43.3 +/- 11) and for GLP-1 by green tea at 120 minutes (165.7 +/- 52).
      The in vitro gastrointestinal digestion process affects the satiety of plant
      extracts, increasing for green tea and decreasing for turmeric. Green tea showed
      the most stable satiating capacity after the in vitro digestion process and this
      may be useful for using it as a stable food supplement to reduce hunger
      associated with overweight and obesity.

PMID- 30226522
TI  - Hydrazone-based covalent organic frameworks for Lewis acid catalysis.
AB  - Hydrazone-based covalent organic frameworks (COFs) are rich in functional groups
      but have very limited variety and applications. Herein, two hydroxy-rich
      hydrazone-based COFs are synthesized in pure water and postsynthetically
      incorporated with CoII, exhibiting Lewis acid catalytic activity towards
      cyanosilylation of various aldehydes with size selectivity.

PMID- 30226523
TI  - Synthesis, characterization, and catalytic evaluation of ruthenium-diphosphine
      complexes bearing xanthate ligands.
AB  - The reaction of [RuCl2(p-cymene)]2 with potassium O-ethylxanthate and a set of
      nine representative Ph2P-X-PPh2 bidentate phosphines (dppm, dppe, dppp, dppb,
      dpppe, dppen, dppbz, dppf, and DPEphos) afforded monometallic
      [Ru(S2COEt)2(diphos)] chelates 1-9 in 62-96% yield. All the products were fully
      characterized by using various analytical techniques and their molecular
      structures were determined by X-ray crystallography. They featured a highly
      distorted octahedral geometry with a S-Ru-S bite angle close to 72 degrees  and P
      Ru-P angles ranging between 73 degrees  and 103 degrees . Bond lengths and IR
      stretching frequencies recorded for the anionic xanthate ligands strongly
      suggested a significant contribution of the EtO+[double bond, length as m
      dash]CS22- resonance form. 1H NMR and XRD analyses showed that the methylene
      protons of the ethyl groups were diastereotopic due to a strong locking of their
      conformation by a neighboring phenyl ring. On cyclic voltammetry, quasi
      reversible waves were observed for the Ru2+/Ru3+ redox couples with E1/2 values
      ranging between 0.65 and 0.80 V vs. Ag/AgCl. The activity of chelates 1-9 was
      probed in three catalytic processes, viz., the synthesis of vinyl esters from
      benzoic acid and 1-hexyne, the cyclopropanation of styrene with ethyl
      diazoacetate, and the atom transfer radical addition of carbon tetrachloride and
      methyl methacrylate. In the first case, 31P NMR analysis of the reaction mixtures
      showed that the starting complexes remained mostly unaltered despite the harsh
      thermal treatment that was applied to them. In the second case, monitoring the
      rate of nitrogen evolution revealed that all the catalysts under investigation
      behaved similarly and were rather slow initiators. In the third case,
      [Ru(S2COEt)2(dppm)] was singled out as a very active and selective catalyst
      already at 140  degrees C, whereas most of the other complexes resisted
      degradation up to 160  degrees C and were only moderately active. Altogether,
      these results were in line with the high stability displayed by
      [Ru(S2COEt)2(diphos)] chelates 1-9.

PMID- 30226524
TI  - Projectile, blunt, or sharp force trauma? A facial lesion on a Bronze Age skull
      from Uglemose, Denmark.
AB  - This study presents and discusses the differential diagnosis of a unique case of
      facial trauma. The adult male skull was excavated in 1948 from Uglemose (Owl Bog)
      outside of Birket, on the island of Lolland (Denmark). Carbon-14 samples from an
      adult tibia excavated with the skull dates to the end of the Danish Bronze Age
      and transition period into the pre-Roman Iron Age. The skull shows a traumatic
      ante-mortem lesion to the left maxilla, directly below the orbit, that opens into
      the maxillary sinus. The left margin of the injury is slightly rounded and angled
      into the lesion while the right margin is pulled out from the lesion and has a
      much sharper border, suggesting a directional force from left to right. A
      previous assessment of the lesion suggested that projectile trauma caused the
      injury, but the lesion does not conclusively demonstrate features of projectile
      trauma. CT scans and 3D visualization of the skull show no evidence of structural
      changes to the maxillary sinus to support a conclusion of projectile trauma.
      Differential diagnosis through macroscopic and microscopic analysis of the lesion
      would suggest rapid blunt force or slow sharp force trauma as a potential
      etiology. The aim of this case study is to discuss the potential mechanisms of
      injury, including type of trauma as well as accidental versus intentional
      etiologies.

PMID- 30226526
TI  - Occurrence, Chronicity and Intensity of Itch in a Clinical Consecutive Sample of
      Patients with Skin Diseases: a Multi-centre Study in 13 European Countries.
AB  - Itch is an unpleasant symptom, affecting many dermatological patients. Studies
      investigating the occurrence and intensity of itch in dermatological patients
      often focus on a single skin disease and omit a control group with healthy skin.
      The aim of this multi-centre study was to assess the occurrence, chronicity and
      intensity (visual analogue scale 0-10) of itch in patients with different skin
      diseases and healthy-skin controls. Out of 3,530 dermatological patients, 54.3%
      reported itch (mean +/- standard deviation itch intensity 5.5 +/- 2.5), while out
      of 1,094 healthy-skin controls 8% had itch (3.6 +/- 2.3). Chronic itch was
      reported by 36.9% of the patients and 4.7% of the healthy-skin controls. Itch was
      most frequent (occurrence rates higher than 80%) in patients with unclassified
      pruritus, prurigo and related conditions, atopic dermatitis and hand eczema.
      However, many patients with psychodermatological conditions and naevi also
      reported itch (occurrence rates higher than 19%).

PMID- 30226527
TI  - Cytophagic Histiocytic Panniculitis Associated with Myelodysplastic Syndrome.

PMID- 30226525
TI  - Roadmap for cardiovascular education across the European Society of Cardiology:
      inspiring better knowledge and skills, now and for the future.
AB  - Aims: The provision of high-quality education allows the European Society of
      Cardiology (ESC) to achieve its mission of better cardiovascular practice and
      provides an essential component of translating new evidence to improve outcomes.
      Methods and results: The 4th ESC Education Conference, held in Sophia Antipolis
      (December 2016), brought together ESC education leaders, National Directors of
      Training of 43 ESC countries, and representatives of the ESC Young Community.
      Integrating national descriptions of education and cardiology training, we
      discussed innovative pathways to further improve knowledge and skills across
      different training programmes and health care systems. We developed an ESC
      roadmap supporting better cardiology training and continued medical education
      (CME), noting: (i) The ESC provides an excellent framework for unbiased and up-to
      date cardiovascular education in close cooperation with its National Societies.
      (ii) The ESC should support the harmonization of cardiology training, curriculum
      development, and professional dialogue and mentorship. (iii) ESC congresses are
      an essential forum to learn and discuss the latest developments in cardiovascular
      medicine. (iv) The ESC should create a unified, interactive educational platform
      for cardiology training and continued cardiovascular education combining
      Webinars, eLearning Courses, Clinical Cases, and other educational programmes,
      along with ESC Congress content, Practice Guidelines and the next ESC Textbook of
      Cardiovascular Medicine. (v) ESC-delivered online education should be integrated
      into National and regional cardiology training and CME programmes. Conclusion:
      These recommendations support the ESC to deliver excellent and comprehensive
      cardiovascular education for the next generation of specialists. Teamwork between
      international, national and local partners is essential to achieve this
      objective.

PMID- 30226528
TI  - Rosacea and Demodicosis: Little-known Diagnostic Signs and Symptoms.
AB  - Papulopustular rosacea and demodicosis are characterized by non-specific
      symptoms, which can make clinical diagnosis difficult. This retrospective study
      of 844 patients assessed the diagnostic importance of clinical signs and symptoms
      that are poorly recognized as being associated with these conditions. In addition
      to well-known signs (vascular signs (present in 80% of patients), papules (39%),
      pustules (22%) and ocular involvement (21%)), other signs and symptoms (discreet
      follicular scales (93%), scalp symptoms (pruritus, dandruff or folliculitis; 38%)
      and pruritus (15%)) may also suggest a diagnosis not only of demodicosis, but
      also of papulopustular rosacea. Facial Demodex densities (measured by 2
      consecutive standardized skin biopsies) were higher when ocular or scalp
      involvement was present, suggesting more advanced disease, but further
      investigations are needed to confirm this hypothesis. Recognition of these
      clinical signs and symptoms should encourage dermatologists to perform a Demodex
      density test, thus enabling appropriate diagnosis to be made.

PMID- 30226529
TI  - Novel Compound Heterozygous Mutations in RAG1 in a Patient with Cutaneous
      Lymphoproliferative Disease.

PMID- 30226530
TI  - Perception of Dermatology and Dermatologists Among Medical Students.

PMID- 30226531
TI  - Phenotypic Features of Epidermolysis Bullosa Simplex due to KLHL24 Mutations in 3
      Italian Cases.

PMID- 30226532
TI  - Progressive Nodular Histiocytosis with Large Nodules and a Bulky Mass.

PMID- 30226533
TI  - MicroRNA-7 inhibits colorectal cancer cell proliferation, migration and invasion
      via TYRO3 and phosphoinositide 3-kinase/protein B kinase/mammalian target of
      rapamycin pathway suppression.
AB  - MicroRNA-7 (miR-7) is a non-coding RNA that inhibits colorectal cancer (CRC) cell
      proliferation, migration and invasion. miR-7 effectively silences TYRO3
      expression, and the close association between TYRO3 and CRC has previously been
      reported. Therefore, the present study aimed to assess the roles and molecular
      mechanisms of TYRO3 and miR-7 in the development of CRC. The expression levels of
      miR-7 and TYRO3 in CRC tissues and cell lines were detected by reverse
      transcription-quantitative polymerase chain reaction. A dual-luciferase reporter
      assay was also performed to confirm whether TYRO3 was a target of miR-7. The
      effect of miR-7 and TYRO3 on cell proliferation, migration and invasion was
      detected in vitro with MTT, wound healing and cell invasion assays, respectively.
      The expression of proteins associated with the phosphoinositide 3-kinase/protein
      kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was detected by
      western blot analysis. The results indicated that the expression of miR-7 was
      downregulated and the levels of TYRO3 were gradually increased in CRC tissues and
      cell lines. TYRO3 was identified as a functional target of miR-7, and its
      expression was negatively regulated by miR-7 in CRC cell lines. The functional
      studies demonstrated that miR-7 knockdown promoted the proliferation, migration
      and invasion of CRC cells, while knockdown of TYRO3 repressed these biological
      processes. In addition, pathway analyses revealed that the oncogenic effect of
      TYRO3 was associated with PI3K/AKT/mTOR pathway inhibition. In conclusion, the
      data suggested that miR-7 promoted the development of CRC by targeting oncogenic
      TYRO3, which may be mediated by inhibition of the PI3K/AKT/mTOR signaling
      pathway. Thus, miR-7 may serve as an independent prognostic biomarker in patients
      with CRC.

PMID- 30226534
TI  - Sulforaphane regulates apoptosis- and proliferation-related signaling pathways
      and synergizes with cisplatin to suppress human ovarian cancer.
AB  - Ovarian cancer is currently the most life-threatening type of gynecological
      malignancy with limited treatment options. Therefore, improved targeted therapies
      are required to combat ovarian cancer across the world. Sulforaphane is found in
      raw cruciferous vegetables. The chemotherapeutic and anti-carcinogenic properties
      of sulforaphane have been demonstrated, however, the underlying mechanisms remain
      to be fully elucidated, particularly in ovarian cancer. In the present study, the
      possibility of repurposing sulforaphane as an anti-ovarian cancer agent was
      examined. Cell viability and colony formation assay were used to test the
      anticancer efficiency of sulforaphane. Then wound healing assay, migration assay,
      cell cycle and apoptosis assays were used to detect how the drug worked on the
      cells. The mechanism of sulforaphane was investigated by western blot analysis.
      It was found that sulforaphane effectively suppressed the progression of human
      ovarian cancer cell proliferation, migration and cell cycle, and promoted
      apoptosis. Sulforaphane inhibited multiple cancer-associated signaling pathways,
      including B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, cytochrome c,
      Caspase-3, phosphorylated AKT, phosphorylated nuclear factor-kappaB, P53, P27,
      Cyclin-D1 and cMyc, and reduced the expression levels of human epidermal growth
      factor receptor 2 in human ovarian cancer cells. Sulforaphane synergized with
      cisplatin to suppress the cancer cell proliferation and enhance ovarian cancer
      cell apoptosis. Xenograft experiments in vivo confirmed that sulforaphane
      effectively suppressed tumor growth by inhibiting ovarian cancer cell
      proliferation through targeting tumor-related signals. The results indicated that
      sulforaphane may be repurposed as an effective anti-ovarian cancer agent, with
      further preclinical or clinical investigations required.

PMID- 30226535
TI  - Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N
      glycosylation.
AB  - Influenza viruses represent a serious threat to human health. Although our
      research group has previously demonstrated the antiviral and anti-inflammatory
      activities of eleutheroside B1, a detailed explanation of the mechanism by which
      it is effective against the influenza virus remains to be elucidated. In the
      present study, the transcriptomic responses of influenza A virus-infected lung
      epithelial cells (A549) treated with eleutheroside B1 were investigated using
      high-throughput RNA sequencing, and potential targets were identified using a
      molecular docking technique, reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR) assay, and DNA methylation analysis. The transcriptomic data
      revealed that there are 1,871 differentially expressed genes (DEGs) between the
      cells infected with the influenza virus strain variant PR8, and the cells
      infected with PR8 and treated with eleutheroside B1. Among the DEGs, RNA
      polymerase II subunit A (POLR2A; encoding the largest subunit of RNA polymerase
      II) and mannosidase alpha class II member 1 (MAN2A1) were selected from the
      molecular docking analysis with eleutheroside B1. The docking score of Drosophila
      melanogaster MAN2A1 (3BVT) was 11.3029, whereas that of POLR2A was 9.0133. The RT
      qPCR results demonstrated that the expression levels of host genes (MAN2A2,
      POLR2A) and viral genes (PA, PB1, PB2, HA) were downregulated following
      eleutheroside B1 treatment. Bisulfite-sequencing PCR was performed to investigate
      whether eleutheroside B1 was able to modify the DNA methylation of POLR2A, and
      the results suggested that the average proportion of methylated CpGs (-222-72 bp)
      increased significantly following treatment with eleutheroside B1. Taken
      together, these findings suggested that eleutheroside B1 may affect N-glycan
      biosynthesis, the chemokine signaling pathway, cytokine-cytokine receptor
      interaction and, in particular, may target the POLR2A to inhibit the production
      of influenza virus genes.

PMID- 30226536
TI  - Bax inhibitor-1 suppresses early brain injury following experimental subarachnoid
      hemorrhage in rats.
AB  - Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is an important
      cause of high mortality and poor prognosis in SAH. B-cell lymphoma 2-associated X
      protein inhibitor-1 (BI-1) is an evolutionarily conserved antiapoptotic protein
      that is primarily located in the membranes of endoplasmic reticulum (ER). BI-1
      has been studied in certain nervous system-associated diseases, but the role of
      this protein in SAH remains unclear. In the present study, the role of BI-1 in
      EBI following SAH was investigated in rat models and its associated mechanisms
      were examined. The SAH rat model was generated by inserting nylon cords into the
      internal carotid artery from the external carotid artery. Samples were assessed
      using neurological scores, brain water content measurements, hematoxylin and
      eosin (H&E) staining, blood-brain barrier (BBB) permeability, terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling and quantitative
      polymerase chain reaction assays, and western blot analyses. It was identified
      that the mRNA and protein levels of BI-1 decreased markedly and were lowest at 24
      h after SAH. BI-1 overexpression and small hairpin RNA (shRNA)-mediated silencing
      markedly suppressed or severely exacerbated EBI following SAH, respectively. BI-1
      overexpression in the SAH model improved neurological scores and decreased the
      brain water content, BBB permeability and levels of apoptosis compared with the
      control and sham groups following SAH. BI-1 shRNA in the SAH model demonstrated
      contrary results. In addition, the mRNA or protein expression levels of ER stress
      associated genes (glucose regulated protein, 78 kDa, C/EBP homologous protein,
      Serine/threonine-protein kinase/endoribonuclease IRE1, c-Jun N terminal kinases
      and apoptotic signaling kinase-1) were markedly suppressed or increased following
      BI-1 overexpression and shRNA-mediated silencing, respectively. The present study
      suggested that BI-1 serves a neuroprotective role in EBI following SAH by
      attenuating BBB disruption, brain edema and apoptosis mediated by ER stress.

PMID- 30226537
TI  - Potential anti-vitiligo properties of cynarine extracted from Vernonia
      anthelmintica (L.) Willd.
AB  - Vitiligo is a depigmentation disorder of the skin. It is primarily caused by the
      destruction of melanocytes or obstruction of the melanin synthesis pathway.
      Melanin is a type of skin pigment that determines skin color. The seeds of
      Vernonia anthelmintica (L.) Willd (Kaliziri) are used for treating skin diseases
      including vitiligo in traditional Uyghur medicine. 1,5-Dicaffeoylquinic acid (1,5
      diCQA) is a natural polyphenolic compound widely distributed in plants and
      extracted from Kaliziri seeds. Therefore, in the present study, the effect of 1,5
      diCQA on melanin synthesis in B16 cell was evaluated, and its molecular mechanism
      was explored. The results indicated that 1,5-diCQA treatment of B16 cells
      stimulated an increase of intracellular melanin level and tyrosinase (TYR)
      activity without cytotoxicity. Reverse transcription quantitative polymerase
      chain reaction results also indicated that 1,5-diCQA may markedly improve the
      protein expression and RNA transcription of microphthalmia-associated
      transcription factor (MITF), melanogenic enzyme Tyr, tyrosinase-related protein 1
      (TRP 1) and tyrosinase-related protein 2 (TRP 2). Additional results identified
      that 1,5-diCQA may promote the phosphorylation of p38 mitogen-activated protein
      kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK) MAPK. Notably,
      the increased levels of intracellular melanin synthesis and tyrosinase expression
      induced by 1,5-diCQA treatment were significantly attenuated by the protein
      kinase A (PKA) inhibitor H-89. Intracellular cyclic adenosine monophosphate
      (cAMP) concentration and phosphorylation of cAMP-response element binding protein
      was increased following 1,5-diCQA treatment. These results indicated that 1,5
      diCQA stimulated melanogenesis via the MAPK and cAMP/PKA signaling pathways in
      B16 cells, which has potential therapeutic implications for vitiligo.

PMID- 30226538
TI  - miR-760 mediates hypoxia-induced proliferation and apoptosis of human pulmonary
      artery smooth muscle cells via targeting TLR4.
AB  - MicroRNAs (miRNAs) have a key role in the pathogenesis of pulmonary arterial
      hypertension (PAH), a disease characterized by enhanced proliferation and reduced
      apoptosis of pulmonary artery smooth muscle cells. In the present study, miR-760
      was demonstrated to be downregulated in PAH lung tissues compared with normal
      lung tissues, an effect that may be associated with the development of PAH.
      Hypoxia is an important stimulus for human pulmonary artery smooth muscle cell
      (hPASMC) proliferation and the occurrence of PAH. Therefore, the effect of miR
      760 in hypoxia-treated and normal hPASMCs was investigated. Expression of
      exogenous miR-760 decreased cell proliferation in hypoxia-induced hPASMCs, and
      promoted cell apoptosis with an increase in the BCL2 associated X/BCL2 ratio and
      the expression levels of Caspase-3 and Caspase-9. In addition, overexpression of
      miR-760 suppressed the migration of hPASMCs under hypoxic conditions.
      Furthermore, miR-760 was demonstrated to mediate its anti-proliferation effect
      via the regulation of toll-like receptor 4 (TLR4), a direct target of miR-760.
      The results revealed that knockdown of TLR4 restrained the hypoxia-induced hPASMC
      proliferation and induced cell apoptosis. The present study uncovered a novel
      regulatory pathway involving miR-760 and suggested that miR-760 may be explored
      as a potential therapy for PAH in the future.

PMID- 30226539
TI  - Breast cancer is associated with methylation and expression of the a disintegrin
      and metalloproteinase domain 33 (ADAM33) gene affected by endocrine-disrupting
      chemicals.
AB  - A disintegrin and metalloproteinase domain 33 (ADAM33) gene is a transmembrane
      glycoprotein that mediates changes in cell adhesion and plays an important role
      in cancer progression. Since bisphenol A (BPA) and phthalates are epigenetically
      toxic, the purpose of this study was to examine whether BPA and phthalate
      metabolites, including monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP),
      mono-isobutyl phthalate (MIBP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl
      5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-carboxypentyl) phthalate
      (MECPP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), have an epigenetic
      impact on ADAM33 and the incidence of breast cancer. CpG islands of breast cancer
      microarray datasets obtained from the Gene Expression Omnibus (GEO) were used to
      assess the ADAM33 methylation profile. We designed a case-control study including
      44 cases and 22 age-matched controls to detect the methylation status of intron 1
      in ADAM33 from peripheral blood mononuclear cells (PBMCs) in blood, using BSP,
      nested PCR, and bisulfite sequencing, and measured the in vivo gene expression of
      ADAM33 and the urinary concentrations of endocrine-disrupting chemicals (EDCs),
      using real-time PCR, high-performance liquid chromatography (HPLC) and liquid
      chromatography-mass spectrometry (LC-MS). Only one dataset, GSE32393, reached
      significance (P=0.016). ADAM33 expression and methylation frequencies at CpG site
      3 in intron 1 were higher in the control group. We found a positive association
      between intron 1 methylation level and ADAM33 expression as well as urinary
      concentrations of MEHHP, MECPP, MEOHP and Sigma4MEHP (the sum of MEHP, MECPP,
      MEHHP, and MEOHP) in the cases. This study suggests that metabolites of phthalate
      such as MEHHP, MECPP, MEOHP and Sigma4MEHP may increase the intron 1 methylation
      level to elevate ADAM33 gene expression and have a protective effect on reducing
      the risk of breast cancer.

PMID- 30226540
TI  - Tanshinone IIA can inhibit MiaPaCa-2 human pancreatic cancer cells by dual
      blockade of the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways.
AB  - Tanshinone IIA (Tan-IIA; C19H18O3) is derived from Danshen (the roots of Salvia
      miltiorrhiza), and has been reported to possess anti-inflammatory and antioxidant
      activities. Tan-IIA can inhibit BxPC-3 human pancreatic cancer cells in vitro
      through inducing endoplasmic reticulum stress and apoptosis via mitochondrial
      pathways. However, the efficacy and molecular mechanisms of Tan-IIA in human
      pancreatic cancer have not yet been elucidated. The transmembrane tyrosine
      kinases, including insulin-like growth factor 1 receptor (IGF1R), vascular
      endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor
      (EGFR) have been implicated in the survival and metastasis of cancer. In
      addition, the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular
      signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/protein kinase
      B (AKT)/mammalian target of rapamycin (mTOR) pathways are the most commonly
      dysregulated kinase cascades in human cancer. The present study aimed to
      investigate the efficacy and molecular mechanisms of Tan-IIA in MiaPaCa-2 human
      pancreatic carcinoma cells. The protein expression levels of EGFR, IGF1R, VEGFR,
      Ras, PI3K, AKT, mTOR, Raf, MEK, ERK and phosphatase and tensin homolog (PTEN)
      were detected in Tan-IIA-treated MiaPaCa-2 cells by western blotting. The results
      demonstrated that the protein expression levels of EGFR, IGF1R, VEGFR, Ras, Raf,
      MEK, ERK, PI3K, AKT, mTOR and PTEN were decreased in MiaPaCa-2 cells treated with
      various concentrations of Tan-IIA for different durations. In conclusion, these
      findings indicated that Tan-IIA may inhibit MiaPaCa-2 human pancreatic cancer
      cells; the molecular mechanisms underlying this inhibitory effect may be involved
      in downregulating EGFR, IGF1R and VEGFR expression, and dual blockade of the
      Ras/Raf/MERK/ERK and PI3K/AKT/mTOR pathways.

PMID- 30226542
TI  - lncRNA LINC01296 regulates the proliferation, metastasis and cell cycle of
      osteosarcoma through cyclin D1.
AB  - Accumulating evidence has indicated that aberrant expression of long non-coding
      RNAs (lncRNAs) is an important oncogenic factor. The aim of the present study was
      to investigate the role of LINC01296, an lncRNA that exerts a tumor-promoting
      function in many cancers, in the regulation of proliferation, metastasis and the
      cell cycle of osteosarcoma. The expression of LINC01296 in osteosarcoma tissues
      and adjacent healthy tissues of 30 patients was analyzed by quantitative real
      time PCR (qRT-PCR). The relationship between LINC01296 expression and the
      survival of patients with osteosarcoma was also explored. The expression levels
      of LINC01296 in osteosarcoma cells and normal cells were compared. LINC01296
      knockdown and overexpression were performed in MG63 and HOS8603 osteosarcoma
      cells by transfecting LINC01296 shRNA and an expression plasmid respectively,
      followed by investigation of the changes on cell proliferation, migration,
      apoptosis and cell cycle arrest. Western blotting was used to analyze the changes
      of cell cycle regulators. Cyclin D1 knockdown and overexpression were carried out
      to verify the interaction between LINC01296 and cyclin D1. LINC01296
      overexpression was demonstrated as a biomarker of osteosarcoma, which was closely
      correlated with the poor survival of patients with osteosarcoma. A high
      expression of LINC01296 was observed in osteosarcoma cells, which was closely
      associated with enhanced proliferation, invasion, and migration of osteosarcoma
      cells. Cyclin D1 expression was positively correlated with the expression of
      LINC01296 in osteosarcoma cells. Cyclin D1 knockdown or overexpression played a
      deterministic role in mediating the effect of LINC01296 on osteosarcoma cells.
      LINC01296 is an oncogenic lncRNA in osteosarcoma. The proliferation, invasion and
      migration of osteosarcoma cells could be effectively retarded by inhibition of
      LINC01296. The cancer-promoting effect of LINC01296 on osteosarcoma was
      determined by cyclin D1.

PMID- 30226541
TI  - The role of 17beta-estradiol-induced upregulation of Piwi-like 4 in modulating
      gene expression and motility in breast cancer cells.
AB  - A majority of breast cancer cases are positive for the estrogen receptor (ER),
      which means that they can respond to the estrogen hormone to achieve growth.
      Hence, the ER signaling pathway has been extensively targeted in pharmaceutical
      research and development in order to suppress tumor growth. However, prevalent
      hormone therapy and targeted therapy often become ineffective as cancer cells
      ultimately develop resistance, suggesting that there could be unidentified
      signaling molecules and events that regulate breast cancer growth. Notably,
      recent studies have uncovered that Piwi-like (Piwil) proteins, which were
      initially found in germline cells, are expressed in a wide spectrum of human
      cancers, including breast cancers. Although Piwil proteins have been well
      established to silence retrotransposons and to promote heterochromatin formation
      in germline cells, their somatic functions in cancer cells remain largely
      unknown. In the present study, we profiled the expression of four Piwi homologs
      in an ER-positive breast cancer cell line, MCF-7, and found that only Piwil4 was
      upregulated by 17beta-estradiol treatment. Notably, Piwil4 upregulation was not
      observed in an ER-positive but non-tumorigenic breast cancer cell line, MCF-12A.
      In addition, the induced expression of Piwil4 was dependent on estrogen/ERalpha
      signaling. To explore the biological significance of Piwil4 in breast cancer
      growth, we knocked down Piwil4 with multiple siRNAs and observed the suppressed
      expression of some canonical targets of ER. The knockdown of Piwil4 expression
      also decreased the migration and invasion capabilities of MCF-7 cells.
      Furthermore, the loss-of-function of Piwil4 reduced the motility of MCF-7 cells
      in wound-healing assays, which could be associated to decreased expression of
      vimentin and N-cadherin. Collectively, these findings revealed that Piwil4 is a
      novel regulator of ER signaling that could be targeted to inhibit breast cancer
      growth and migration.

PMID- 30226543
TI  - Characterization of selective exosomal microRNA expression profile derived from
      laryngeal squamous cell carcinoma detected by next generation sequencing.
AB  - Exosomes are nanometer-scale extracellular vesicles derived from almost all types
      of cells and key signaling mediators between cancer cells and their
      microenvironment. Certain microRNAs (miRNAs) are selected for exosome packing and
      exclusion from parental cells, while other miRNAs are selectively retained by
      cells, suggesting a biological role for these miRNAs in tumor malignant
      progression. In the present study, we isolated and characterized the exosomes
      derived from the laryngeal squamous cell carcinoma (LSCC) cell line AMC-HN-8 for
      the first time, and identified a subset of miRNAs enriched in the exosomes
      compared with parental cells, such as miR-1246, miR-1290, miR-335-5p, miR-127-3p
      and miR-122-5p through small RNA sequencing combined with reverse transcription
      quantitative PCR (RT-qPCR) analysis. Potential target prediction, Gene Ontology
      (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
      enrichment analysis revealed possible functions associated with these selective
      exosomal miRNAs. In conclusion, the present study demonstrated that the LSCC cell
      line AMC-HN-8 can release exosomes and cells can selectively pack certain miRNAs
      into exosomes.

PMID- 30226544
TI  - Dermcidin as a novel binding protein of lncRNA STCAT3 and its effect on prognosis
      in gastric cancer.
AB  - Long non-coding RNAs (lncRNAs) perform distinct biological functions by
      regulating gene expression through various molecular mechanisms under normal
      physiological and pathological conditions. However, the function of the stomach
      cancer-associated transcript-3 (STCAT3) lncRNA, including its prognostic
      significance and role as a binding protein in gastric cancer (GC), remain
      unclear. In the present study, 56 potential binding proteins of STCAT3 were
      screened using through mass spectrometry and bioinformatics analysis. Among
      these, dermcidin, GAPDH, annexin, calmodulin-like protein, cathepsin-D and
      suprabasin were demonstrated to be candidate binding proteins using a literature
      search. RNA-protein interaction prediction was used to confirm these six
      proteins. Finally, dermcidin was identified as the binding protein of STCAT3 by
      comparing the mRNA and protein levels of the candidate genes and their
      correlations with STCAT3 in plasmid-transfected BGC-823 GC cell lines, as well as
      by validating the interplay between dermcidin and STCAT3 in other GC cell lines.
      Immunohistochemical analysis of tissues from 98 patients with GC further
      confirmed the interaction between dermcidin and STCAT3. The results of the
      present study also revealed that STCAT3 and dermcidin and independent predictors
      of overall survival in patients with GC. Furthermore STCAT3 and dermcidin are
      positively correlated with lymph node metastasis and tumor/node/metastasis score.
      In summary, the present study suggests that dermcidin is a novel binding protein
      of lncRNA STCAT3, which serves an important role in the progress and clinical
      outcome of GC.

PMID- 30226545
TI  - Prediction of candidate RNA signatures for recurrent ovarian cancer prognosis by
      the construction of an integrated competing endogenous RNA network.
AB  - Tumor recurrence hinders treatment of ovarian cancer. The present study aimed to
      identify potential biomarkers for ovarian cancer recurrence prognosis and explore
      relevant mechanisms. RNA-sequencing of data from the TCGA database and GSE17260
      dataset was carried out. Samples of the data were grouped according to tumor
      recurrence information. Following data normalization, differentially expressed
      genes/micro RNAs (miRNAs)/long non-coding (lncRNAs) (DEGs/DEMs/DELs) were
      selected between recurrent and non-recurrent samples. Their correlations with
      clinical information were analyzed to identify prognostic RNAs. A support vector
      machine classifier was used to find the optimal gene set with feature genes that
      could conclusively distinguish different samples. A protein-protein interaction
      (PPI) network was established for DEGs using relevant protein databases. An
      integrated 'lncRNA/miRNA/mRNA' competing endogenous RNA (ceRNA) network was
      constructed to reveal potential regulatory relationships among different RNAs. We
      identified 36 feature genes (e.g. TP53 and RBPMS) for the classification of
      recurrent and non-recurrent ovarian cancer samples. Prediction with this gene set
      had a high accuracy (91.8%). Three DELs (WT1-AS, NBR2 and ZNF883) were highly
      associated with the prognosis of recurrent ovarian cancer. Predominant DEMs with
      their targets were hsa-miR-375 (target: RBPMS), hsa-miR-141 (target: RBPMS), and
      hsa-miR-27b (target: TP53). Highlighted interactions in the ceRNA network were
      'WT1-AS-hsa-miR-375-RBPMS' and 'WT1-AS--hsa-miR-27b-TP53'. TP53, RBPMS, hsa-miR
      375, hsa-miR-141, hsa-miR-27b, and WT1-AS may be biomarkers for recurrent ovarian
      cancer. The interactions of 'WT1-AS-hsa--miR-375-RBPMS' and 'WT1-AS-hsa-miR-27b
      TP53' may be potential regulatory mechanisms during cancer recurrence.

PMID- 30226546
TI  - An integrated methylation and gene expression microarray analysis reveals
      significant prognostic biomarkers in oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is a life-threatening disease with a poor
      prognosis. Although previous studies have reported that the methylation of
      certain genes is associated with the pathogenesis of OSCC, the methylation of
      genes that have relevance to OSCC progression is not clearly documented. The
      present study aimed to gain insights into the mechanisms underlying DNA
      methylation regulation associated with OSCC progression and to identify potential
      prognostic markers for OSCC treatment. DNA methylation dataset GSE41114 and gene
      expression dataset GSE74530 were downloaded from the Gene Expression Omnibus
      database. The global methylation status of OSCC tumor samples and normal control
      samples was determined, and differentially methylated genes (DMGs) in OSCC
      samples compared with control samples were identified. The mRNA expression data
      were then integrated to identify differentially expressed genes (DEGs) in OSCC
      samples compared with control samples. Overlapping genes between DEGs and DMGs
      were identified, and functional enrichment analysis was performed. In addition,
      survival analysis of the overlapping genes was performed to screen genes with
      prognostic significance in OSCC. A total of 40,115 differential methylation CpG
      sites spanning 3,360 DMGs were identified; CpG sites in the promoter, gene body
      and intergenic regions were generally highly hypermethylated or hypomethylated.
      Additionally, 508 DEGs in OSCC samples were identified, including 332 upregulated
      and 176 downregulated genes. A total of 82 overlapping genes between DEGs and
      DMGs were found, which were mainly involved in protein metabolism, regulation of
      the metabolic process and the immune system. Additionally, differential
      methylation or expression of several genes, including fibroblast activation
      protein alpha (FAP), interferon alpha inducible protein 27 (IFI27), laminin
      subunit gamma2 (LAMC2), matrix metallopeptidase 1 (MMP1), serine peptidase
      inhibitor Kazal-type 5 (SPINK5) and zinc finger protein 662 (ZNF662), was
      significantly associated with the survival of OSCC patients, and their
      differential expression in OSCC patients was further confirmed by reverse
      transcription-quantitative polymerase chain reaction in OSCC and normal oral cell
      lines. Overall, FAP, IFI27, LAMC2, MMP1, SPINK5 and ZNF662 genes caused by
      epigenetic changes via DNA methylation may be associated with the development and
      progression of OSCC, and should be valuable OSCC therapeutic biomarkers.

PMID- 30226547
TI  - Identification of potential biomarkers in cholestasis and the therapeutic effect
      of melatonin by metabolomics, multivariate data and pathway analyses.
AB  - The present study investigated the anti-cholestatic effect of melatonin (MT)
      against alpha-naphthyl isothiocyanate (ANIT)-induced liver injury in rats and
      screened for potential biomarkers of cholestasis. Rats were administered ANIT by
      intraperitoneal injection and then sacrificed 36 h later. Serum biochemical
      parameters were measured and liver tissue samples were subjected to histological
      analysis. Active components in the serum were identified by gas chromatography
      mass spectrometry, while biomarkers and biochemical pathways were identified by
      multivariate data analysis. The results revealed that the serum levels of alanine
      aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin,
      gamma-glutamyl transpeptidase, and alkaline phosphatase were reduced in rats with
      ANIT-induced cholestasis that were treated with MT. The histological observations
      indicated that MT had a protective effect against ANIT-induced hepatic tissue
      damage. Metabolomics analysis revealed that this effect was likely to be
      associated with the regulation of compounds related to MT synthesis and
      catabolism, and amino acid metabolism, including 5-aminopentanoate, 5
      methoxytryptamine, L-tryptophan, threonine, glutathione, L-methionine, and
      indolelactate. In addition, principal component analysis demonstrated that the
      levels of these metabolites differed significantly between the MT and control
      groups, providing further evidence that they may be responsible for the effects
      induced by MT. These results provide an insight into the mechanisms underlying
      cholestasis development and highlight potential biomarkers for disease diagnosis.

PMID- 30226548
TI  - Prognostic value of monocarboxylate transporter 4 in patients with esophageal
      squamous cell carcinoma.
AB  - Monocarboxylate transporter 4 (MCT4) is a membrane transporter of
      monocarboxylates that has been reported to play an important role in
      tumorigenesis and progression in several solid tumor types. The present study
      aimed to investigate its clinical significance in esophageal squamous cell
      carcinoma (ESCC). After obtaining and analyzing MCT4 mRNA expression data from
      The Cancer Genome Atlas (TCGA) database, the prognostic potential of MCT4 was
      evaluated by IHC analysis. The effect of the knockdown of MCT4 by shRNA was also
      evaluated using Cell Counting Kit-8 (CCK-8) and clonogenic assays, in order to
      determine whether MCT4 inhibition affected the proliferation and survival ability
      of ESCC cells. Flow cytometric analysis was used to evaluate apoptosis. Western
      blot analysis was performed to detect the expression levels of p-Akt, Bax, Bcl-2,
      cytoplasmic cytochrome c and cleaved caspase-3. MCT4 expression was associated
      with T stage (P=0.001), N stage (P=0.020) and formalin-fixed and paraffin
      embedded (TNM) stage (P=0.042). Kaplan-Meier survival analysis indicated that
      patients in the high-MCT4 group had a lower overall survival (OS) rate (P=0.001)
      and progression-free survival (PFS) rate (P=0.003). The univariate Cox regression
      analysis and multivariate Cox regression analysis results indicated that MCT4 is
      an independent predictor of OS (P=0.001 and 0.014) and PFS (P=0.004 and 0.046).
      Downregulation of MCT4 inhibited cell proliferation and increased apoptosis in
      vitro. The proliferation rate and clone numbers were decreased and apoptotic
      rates were increased in the sh-MCT4 groups (all P<0.05). Furthermore, MCT4
      knockdown reduced the activation of Akt and increased Bax/Bcl-2 ratios,
      cytochrome c release and caspase-3 cleavage (all P<0.05). Consequently, MCT4
      could serve as a promising biomarker for ESCC to identify patients with poor
      prognosis.

PMID- 30226549
TI  - Circadian clock gene Per2 downregulation in non-small cell lung cancer is
      associated with tumour progression and metastasis.
AB  - Period2 (Per2) is a key circadian clock gene, and its deregulation contributes to
      tumour development, including breast cancer. However, the biological function and
      clinicopathological significance of Per2 in non-small cell lung cancer (NSCLC)
      remain unclear. The present study aimed to explore the role of Per2 and its
      relative clinical significance in NSCLC. To analyse Per2 expression in NSCLC
      specimens, reverse transcription-quantitative polymerase chain reaction was
      performed, and the results indicated that Per2 expression was markedly
      downregulated in 83.87% (26/31) of NSCLC samples compared with their adjacent
      matched tissues. Increased Per2 expression was associated with increased
      differentiation (P<0.01) and reduced lymph node metastasis (P<0.0001). Functional
      studies identified that enhancing Per2 expression in A549 cells by lentivirus
      transduction not only significantly suppressed cell growth, migration and
      invasion (P<0.05) but also inhibited NSCLC growth and metastasis in vivo. Animal
      studies and histopathological analysis identified that Per2 expression in A549
      cells not only markedly increased expression of tumour anti-oncogenes Bax, P53
      and P21 but also inhibited expression of pro-oncogenes vascular endothelial
      growth factor, CD44 and c-Myc. These results indicate that the loss of Per2 is
      one of the factors underlying tumourigenesis in NSCLC, and it may function as a
      novel molecular target for NSCLC.

PMID- 30226550
TI  - MALAT1 promotes angiogenesis of breast cancer.
AB  - Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non
      coding RNA (lncRNA) that has an oncogenic role in some types of cancers,
      uncluding breast cancer (BC). To investigate the role of MALAT1 in human BC
      progression, we detected MALAT1 expression levels based on tissue samples from 20
      BC cases and 20 healthy controls and found MALAT1 expression levels to be
      significantly high (P<0.05). Then, we knocked down endogenous MALAT1 in MCF-7
      cells using MALAT1 short hairpin RNA (shRNA). The results revealed that MALAT1
      knockdown could significantly inhibit proliferation, migration, and tube
      formation in vitro. In addition, miR-145 expression inversely changed in BC
      tissue cases. Furthermore, knockdown of endogenous MALAT1 significantly increased
      miR-145 levels in MCF-7 cells. This finding indicated an interaction between
      MALAT1 and miR-145. In addition, knockdown of MALAT1 significantly reduced the
      expression of vascular endothelial growth factor in MCF-7 cells. This outcome
      revealed that MALAT1 promoted angiogenesis in BC, which may be related to the
      expression of miR-145.

PMID- 30226551
TI  - Interaction of hematopoietic CD34+ CD45+ stem cells and cancer cells stimulated
      by TGF-beta1 in a model of glioblastoma in vitro.
AB  - The majority of modern treatment methods for malignant brain tumors are not
      sufficiently effective, with a median survival time varying between 9 and 14
      months. Metastatic and invasive processes are the principal characteristics of
      malignant tumors. The most important pathogenic mechanism is epithelial
      mesenchymal transition (EMT), which causes epithelial cells to become more
      mobile, and capable of invading the surrounding tissues and migrating to distant
      organs. Transforming growth factor-beta1 (TGF-beta1) serves a key role in EMT
      inducing mechanisms. The current study presented the interaction between
      hematopoietic stem cells and glioblastoma cells stimulated by TGF-beta1 in vitro.
      The materials for the study were hematopoietic progenitor cell antigen CD34+
      hematopoietic stem cells (HSCs) and U87 glioblastoma cells. Cell culture methods,
      automated monitoring of cell-cell interactions, confocal laser microscopy, flow
      cytometry and electron microscopy were used. It was demonstrated that U87 cells
      have a complex communication system, including adhesive intercellular contacts,
      areas of interdigitation with dissolution of the cytoplasm, cell fusion,
      communication microtubes and microvesicles. TGF-beta1 affected glioblastoma cells
      by modifying the cell shape and intensifying their exocrine function. HSCs
      migrated to glioblastoma cells, interacted with them and exchanged fluorescent
      tags. Stimulation of cancer cells with TGF-beta1 weakened the ability of
      glioblastoma cells to attract HSCs and exchange a fluorescent tag. This process
      stimulated cancer cell proliferation, which is an indication of the ability of
      HSCs to 'switch' the proliferation and invasion processes in glioblastoma cells.

PMID- 30226552
TI  - Decreased human antigen R expression confers resistance to tyrosine kinase
      inhibitors in epidermal growth factor receptor-mutant lung cancer by inhibiting
      Bim expression.
AB  - Primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors
      (EGFR-TKIs) is an obstacle for the treatment of non-small cell lung cancer
      (NSCLC); however, the associated mechanisms are not well understood. Studies have
      reported that Bim expression levels may be associated with the efficacy of EGFR
      TKI treatment in NSCLC patients harboring EGFR mutations. Human antigen R (HuR)
      regulates the mRNA and protein expression of target genes, including certain B
      cell lymphoma 2 family members. The present study investigated whether HuR
      mediates resistance to EGFR-TKIs via the regulation of Bim. The results
      demonstrated that decreased levels of HuR and Bim protein expression are
      associated with primary resistance to EGFR-TKIs and reduced median progression
      free survival in NSCLC patients. In vitro assays also revealed that knockdown of
      HuR resulted in primary EGFR-TKI resistance and reduced gefitinib-induced
      apoptosis in HCC827 cells by decreasing Bim expression. Furthermore, elevated HuR
      expression restored gefitinib sensitivity and enhanced gefitinib-induced
      apoptosis in H1650 cells by increasing Bim expression. In vivo, it was further
      demonstrated that overexpression of HuR was able to restore the gefitinib
      sensitivity of H1650 cells. Therefore, altered HuR/Bim expression is proposed to
      be a novel mechanism of EGFR-TKI resistance in NSCLC.

PMID- 30226554
TI  - Jam3 promotes migration and suppresses apoptosis of renal carcinoma cell lines.
AB  - As a common type of renal cancer, renal cell carcinoma (RCC) has a high annual
      mortality rate. The incidence of RCC has been increasing in China and worldwide.
      A large number cases of RCC are diagnosed at late stages, often with local and/or
      systematic metastasis. Surgical resection of RCC is only suitable for a small
      number of patients with early stage tumors, and thus, novel therapeutic methods
      are required. Junctional adhesion molecule 3 (Jam3) is a member of the junctional
      adhesion molecule family, which has been linked to epithelial and cancer cell
      proliferation. The present study investigated whether the Jam3 gene affected RCC
      growth via proliferation and apoptosis. The expression and biological function of
      Jam3 in renal carcinoma cells was investigated. The mRNA and protein levels of
      Jam3 were examined by reverse transcription-polymerase chain reaction and western
      blot analyses. The role of Jam3 in the migration and apoptosis of renal carcinoma
      cells was determined using small interfering RNA, wound-healing assays, flow
      cytometry, and cell migration assays. In the cell migration assays, E-cadherin, N
      cadherin, integrin beta1, and matrix metalloproteinase (MMP)-2 proteins were
      detected by western blot analysis. It was shown that the expression of Jam3 was
      significantly elevated in human renal carcinoma cells compared with that in renal
      tubular epithelial cells. The knockdown of Jam3 inhibited renal carcinoma cell
      migration and promoted renal carcinoma cell apoptosis. It also increased the
      protein levels of E-cadherin and reduced the protein levels of N-cadherin,
      integrin beta1 and MMP-2. The inhibition of Jam3 promoted migration and
      suppressed apoptosis of renal carcinoma cells via regulation of the expression of
      E-cadherin, N-cadherin, integrin beta1 and MMP-2. Therefore, Jam3 was suggested
      as a novel target gene for the diagnosis and treatment of RCC.

PMID- 30226553
TI  - Pterostilbene inhibits nutrient metabolism and induces apoptosis through AMPK
      activation in multiple myeloma cells.
AB  - Multiple myeloma (MM) cells are characterized by an abnormal nutrient metabolism
      that is distinct from normal plasma cells. Pterostilbene (PTE), a bioactive
      component of blueberries, has been demonstrated to induce apoptosis in multiple
      types of cancer cell. The present study evaluated whether PTE treatment affected
      the survival of MM cells from a metabolic perspective, and the potential
      mechanisms of this. It was observed that the administration of PTE induced
      apoptosis, which was mediated by the increased activation of AMP-activated
      protein kinase (AMPK). Once activated, AMPK decreased the expression and/or
      activity of key lipogenic enzymes, including fatty acid synthase and acetyl-CoA
      carboxylase. In addition, the activation of AMPK suppressed the downstream
      substrate, mechanistic target of rapamycin, which dephosphorylated eukaryotic
      initiation factor 4E-binding protein 1, leading to a general decrease in mRNA
      translation. Pre-treatment with the AMPK inhibitor compound C prior to PTE
      treatment compromised the anti-myeloma apoptosis effect, suggesting the critical
      role of AMPK in mediating PTE-induced cell toxicity. Consistent results were
      obtained in vivo. Finally, autophagy was adaptively upregulated subsequent to PTE
      treatment; the pro-apoptotic efficacy of PTE was potentiated once autophagic flux
      was inhibited by 3-methyladenine. Taken together, these data demonstrated that
      PTE exerts anti-tumor effects on MM cells via AMPK-induced nutrient suppression.

PMID- 30226555
TI  - Deduction of novel genes potentially involved in hypoxic AC16 human
      cardiomyocytes using next-generation sequencing and bioinformatics approaches.
AB  - Atherosclerotic cardiovascular disease and acute myocardial infarction are the
      leading causes of mortality worldwide, and apoptosis is the major pathway of
      cardiomyocyte death under hypoxic conditions. Although studies have reported
      changes in the expression of certain pro-apoptotic and anti-apoptotic genes in
      hypoxic cardiomyocytes, genetic regulations are complex in human cardiomyocytes
      and there is much that remains to be fully elucidated. The present study aimed to
      identify differentially expressed genes in hypoxic human AC16 cardiomyocytes
      using next-generation sequencing and bioinformatics. A total of 24 genes (15
      upregulated and 9 downregulated) with potential micro (mi)RNA-mRNA interactions
      were identified in the miRmap database. Utilising the Gene Expression Omnibus
      database of cardiac microvascular endothelial cells, tensin 1, B-cell lymphoma 2
      interacting protein 3 like, and stanniocalcin 1 were found to be upregulated, and
      transferrin receptor and methyltransferase like 7A were found to be downregulated
      in response to hypoxia. Considering the results from miRmap, TargetScan and miRDB
      together, two potential miRNA-mRNA interactions were identified: hsa-miRNA (miR)
      129-5p/CDC42EP3 and hsa-miR-330-3p/HELZ. These findings contribute important
      insights into possible novel diagnostic or therapeutic strategies for targeting
      cardiomyocytes under acute hypoxic stress in conditions, including acute
      myocardial infarction. The results of the present study also introduce an
      important novel approach in investigating acute hypoxic pathophysiology.

PMID- 30226556
TI  - Oral administration of Cervus nippon mantchuricus extract suppresses 2,4
      dinitrochlorobenzene-induced atopic dermatitis in BALB/c mice and inflammatory
      effects in mast cells.
AB  - Cervus nippon mantchuricus extract, known as nok-gol (NGE) in Korean, is useful
      for the treatment of various inflammatory diseases, including bone resorption and
      neutropenia. However, NGE has not been widely investigated, and its efficacy and
      safety remain to be fully elucidated. In the present study, histological
      analysis, blood analysis, reverse transcription-semi-quantitative polymerase
      chain reaction analysis and enzyme-linked immunosorbent assays were performed to
      verify the inhibitory effect of NGE on atopic dermatitis (AD) in BALB/c mice and
      on inflammatory effects in HMC-1 human mast cells. NGE suppressed the development
      of AD in mice, and decreased the infiltration of inflammatory cells, mast cells
      and CD4+ T cells into AD skin lesions. NGE also decreased leukocyte levels
      induced by 2,4-dinitrochlorobenzene (DNCB). NGE alleviated AD-like inflammatory
      symptoms in mice by suppressing the production of CD4+ T cells. NGE downregulated
      the mRNA expression of inflammatory cytokines induced by DNCB. It also decreased
      the serum immunoglobulin E concentration and inflammatory cytokine levels in DNCB
      treated BALB/c mice. The in vitro experiments demonstrated that NGE reduced the
      phorbol 12-myristate 13-acetate + ionomycin-induced expression of pro
      inflammatory cytokines interleukin (IL)-4, IL-13, tumor necrosis factor-alpha,
      and IL-6 in HMC-1 cells. Taken together, the results of the present study
      indicated that NGE suppressed the progression of DNCB-induced AD in BALB/c mice
      and reduced inflammatory effects in HMC-1 cells. This suggests that NGE may be a
      useful drug for the treatment of AD.

PMID- 30226557
TI  - The active participation of p22phox-214T/C in the formation of intracranial
      aneurysm and the suppressive potential of edaravone.
AB  - Oxidative stress reactions play an important role in the pathogenesis of
      intracranial aneurysm (IA). p22phox is involved in the oxidative stress reaction,
      and it is a critical subunit of nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase. The present study investigated the association of genetic
      variants within the gene encoding p22phox-214T/C with IA. The p22phox-214T/C gene
      polymorphisms in 192 cases of IA and 112 controls were analyzed by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP). The mRNA
      expression of NADPH oxidase was also analyzed by RT-PCR. The results of RT-PCR
      were validated by ELISA. In a rabbit model of elastase-induced aneurysm, we used
      edaravone for anti-oxidative stress treatment to observe the curative effects. In
      the clinical cases, a significant difference in p22phox-214T/C allele frequencies
      in the IA group was observed compared with the control group (P<0.001). The
      expression level of NADPH oxidase was differed significantly between the IA group
      and the control group. In the rabbit model of elastase-induced aneurysm, the
      success rate of the aneurysmal model in the edaravone group and the wound ulcer
      rate were lower than those in the control group. In addition, the diameter of the
      aneurysm was smaller than in the edaravone group than in the control group
      (3.26+/-0.13 mm vs. 3.85+/-0.07 mm), and the expression of matrix
      metalloproteinase-9 (MMP-9) was significantly lower than that in the control
      group (P<0.0001). Thus, these data suggest the active participation of p22phox
      214T/C in the formation of IA and the suppressive potential of edaravone against
      IA formation.

PMID- 30226558
TI  - Inhibition of lysyl oxidase expression by dextran sulfate affects invasion and
      migration of gastric cancer cells.
AB  - In the present study, the effect of dextran sulfate (DS) on the metastasis and
      invasion of human gastric cancer cells and its key underlying mechanism were
      investigated. The levels of hypoxia-inducible factor 1alpha (HIF-1alpha),
      transforming growth factor beta (TGF-beta) and lysyl oxidase (LOX) expression
      were evaluated in human gastric cancer and peritumoral tissues by
      immunohistochemical analysis. Cell proliferation and apoptosis were also examined
      using the Cell Counting Kit-8 assay and flow cytometry. The effect of DS on the
      invasion and migration of BGC-823 cells was assessed using a Transwell assay. BGC
      823 cells were divided into the control (phosphate-buffered saline-treated) and
      experimental (DS-treated) groups, and cultured for different times under hypoxic
      conditions. Subsequently, LOX and TGF-beta expression levels in the cells were
      measured by immunocytochemistry, immunofluorescence, reverse transcription
      quantitative polymerase chain reaction and western blot analysis. HIF-1alpha, TGF
      beta and LOX expression levels were significantly higher in human gastric cancer
      tissues as compared with that in adjacent tissues. DS influenced cell
      proliferation and apoptosis in a dose-dependent manner. Furthermore, DS reduced
      the number of invaded and migrated cells. Under hypoxic conditions, DS reduced
      HIF-1alpha, TGF-beta and LOX expression levels in BGC-823 cells. After 12 h, the
      effect of combination of DS and beta-aminopropionitrile (BAPN) on LOX and TGF
      beta protein levels was more significant compared with that of DS or BAPN alone.
      Therefore, DS may inhibit the invasion and migration of human gastric cancer
      cells under hypoxic conditions by influencing LOX.

PMID- 30226559
TI  - Treatment of type 2 diabetes mellitus via reversing insulin resistance and
      regulating lipid homeostasis in vitro and in vivo using cajanonic acid A.
AB  - The present study investigated the effects of cajanonic acid A (CAA), extracted
      from the leaves of Cajanus cajan (L.) Millsp with a purity of 98.22%, on the
      regulatory mechanisms of glucose and lipid metabolism. HepG2 cells transfected
      with a protein-tyrosine phosphatase 1B (PTP1B) overexpression plasmid were
      established. The cells, induced with insulin resistance by dexamethasone (Dex)
      treatment, together with type 2 diabetes mellitus (T2DM) model rats and ob/ob
      mice, were used in the present study. The effects of CAA treatment on the
      differentiation of 3T3-L1 adipocytes were determined using Oil Red O. The
      expression levels of insulin signaling factors were detected via reverse
      transcription-quantitative polymerase chain reaction and western blot analyses.
      The results revealed that the overexpression of PTP1B contributed to insulin
      resistance, which was reversed by CAA treatment via inhibiting the activity of
      PTP1B and by regulating the expression of associated insulin signaling factors.
      The treatment of cell lines with Dex led to increased expression of PTP1B but
      decreased glucose consumption, and decreased tyrosine phosphorylation of insulin
      receptor, insulin receptor substrate 1, and phosphoinositide 3-kinase. Treatment
      with CAA not only reduced the fasting blood glucose levels and protected organs
      from damage, but also reduced the serum fasting levels of total cholesterol,
      triglycerides and low-density lipoprotein cholesterol in the T2DM rats. CAA
      treatment also inhibited adipocyte differentiation and decreased the mRNA levels
      of various adipogenic genes. Furthermore, CAA treatment restored the transduction
      of insulin signaling by regulating the expression of PTP1B and associated insulin
      signaling factors. Treatment with CAA also reduced the problems associated with
      hyperglycemia and hyperlipidemia. In conclusion, CAA may be used to cure T2DM via
      restoring insulin resistance and preventing obesity.

PMID- 30226560
TI  - The effect of curcumin on the differentiation, apoptosis and cell cycle of neural
      stem cells is mediated through inhibiting autophagy by the modulation of Atg7 and
      p62.
AB  - Curcumin is an orange-yellow colored, lipophilic polyphenol substance derived
      from the rhizome of Curcuma longa that is widely used in many countries. Curcumin
      has many reported functions, including antioxidant and anti-inflammatory effects.
      Autophagy removes damaged organelles and protein aggregates in the cell. However,
      whether curcumin mediates its effects on neural stem cell (NSC) differentiation,
      cell cycle and apoptosis through autophagy is unknown. In the present study, the
      effects of curcumin and 3-methyladenine (3MA; an autophagy inhibitor, as a
      positive control) on the autophagy, differentiation, cell cycle progression and
      apoptosis of NSCs in different culture states were examined. In order to confirm
      the role of autophagy in these processes of NSC behavioral change, the protein
      expression level changes of markers of autophagy, such as autophagy-related
      protein 7 (Atg7), light chain (LC)3 and p62, were assessed. When NSCs were in an
      adherent state, 10 uM curcumin inhibited their differentiation into GFAP+
      astrocytes or DCX+ immature neurons, while Atg7 and p62 protein expression were
      also reduced compared with the untreated control group. When NSCs were in a
      suspended state, 10 uM curcumin inhibited the cell cycle progression and
      apoptosis of NSCs as determined by western blotting, which was associated with a
      decreased autophagic flux and Atg7 expression. In addition, the curcumin-treated
      group trended in a similar direction to the 3MA-treated group. Thus, the data
      suggest that curcumin can inhibit differentiation, promote cell survival and
      inhibit cell cycle progression from G1 to S in NSCs, and that these effects are
      mediated through the regulation of Atg7 and p62.

PMID- 30226561
TI  - Upregulation of macrophage migration inhibitory factor promotes tumor metastasis
      and correlates with poor prognosis of pancreatic ductal adenocarcinoma.
AB  - Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that
      serves important roles in cancer. MIF overexpression is frequently observed in
      numerous human cancer types, including pancreatic carcinoma. However, the
      prognostic value and function of MIF in pancreatic ductal adenocarcinoma (PDAC)
      have not been fully elucidated. In the present study, upregulation of MIF
      expression in PDAC tissue compared with adjacent normal tissue was observed.
      Furthermore, MIF overexpression was identified to be significantly associated
      with poor survival rates in patients with PDAC. Multivariate Cox regression
      analysis confirmed that MIF was an independent risk factor for poor survival.
      Functional analyses demonstrated that MIF knockdown significantly inhibited the
      proliferation and invasion of pancreatic cancer cells in vitro compared with
      control cells. IN addition, mechanistic investigations revealed that silencing
      MIF leads to inhibition of AKT serine/threonine kinase and extracellular-signal
      regulated kinase activation, and suppression of cyclin D1 and matrix
      metalloproteinase-2 expression, which may suppress tumor proliferation and
      invasion. These results highlight the importance of MIF overexpression in PDAC
      aggressiveness, and indicate that MIF may be a potential therapeutic target for
      pancreatic cancer.

PMID- 30226562
TI  - GPR17 mediates ischemia-like neuronal injury via microglial activation.
AB  - GPR17 is a G (i)-coupled dual receptor, linked to P2Y and CysLT receptors
      stimulated by uracil nucleotides and cysteinyl leukotrienes, respectively. Recent
      evidence has demonstrated that GPR17 inhibition ameliorates the progression of
      cerebral ischemic injury by regulating neuronal death and microglial activation.
      The present study aimed to assess the detailed regulatory roles of this receptor
      in oxygen-glucose deprivation/recovery (OGD/R)-induced ischemia-like injury in
      vitro and explore the underlying mechanism. The results demonstrated that OGD/R
      induced ischemic neuronal injury and microglial activation, including enhanced
      phagocytosis and increased inflammatory cytokine release in neuron-glial mixed
      cultures of cortical cells. GPR17 upregulation during OGD/R was spatially and
      temporally correlated with neuronal injury and microglial activation. In
      addition, GPR17 knockdown inhibited OGD/R-induced responses in neuron-glial mixed
      cultures. GPR17 knockdown also attenuated cell injury induced by the agonist
      leukotriene D4 (LTD4) or uridine 5'-diphosphate (UDP) in neuron-glial mixed
      cultures. However, GPR17 knockdown did not affect OGD/R-induced ischemic neuronal
      injury in primary cultures of neurons. In primary astrocyte cultures, neither
      GPR17 nor OGD/R induced injury. By contrast, GPR17 knockdown ameliorated OGD/R
      induced microglial activation, boosting phagocytosis and inflammatory cytokine
      release in primary microglia cultures. Finally, the results demonstrated that the
      conditioned medium of microglia pretreated with OGD/R induced neuronal death, and
      the neuronal injury was significantly inhibited by GPR17 knockdown. These
      findings suggested that GPR17 may mediate ischemia-like neuronal injury and
      microglial activation in vitro; however, the protective effects on ischemic
      neuronal injury might depend upon microglial activation. Whether GPR17 regulates
      neuronal injury mediated by oligodendrocyte linkage remains to be investigated.

PMID- 30226563
TI  - Downregulation of glucose-regulated protein 78 enhances the cytotoxic effects of
      curcumin on human nasopharyngeal carcinoma cells.
AB  - Curcumin is a conventional Chinese medicine, which exerts a marked effect on
      various tumor types and suppresses tumor invasion. The present study analyzed the
      antineoplastic effects of curcumin on human nasopharyngeal carcinoma (NPC) cells
      and determined the effects of endoplasmic reticulum (ER) stress on curcumin
      induced cytotoxicity. The Cell Counting Kit-8 assay examined the viability of
      SUNE1 and SUNE2 NPC cells. The Annexin V/propidium iodide staining technique was
      used to detect cell apoptosis and flow cytometry was used to examine cell cycle
      distribution. Western blotting and immunofluorescence were used to detect ER
      stress-associated molecules. Furthermore, the toxic effects of curcumin treatment
      alongside glucose-regulated protein 78 (GRP78) knockdown using small interfering
      (si)RNA, and treatment with the pan-caspase inhibitor Z-VAD-FMK and the protein
      kinase B (AKT) inhibitor MK-2206 were detected. The results demonstrated that
      curcumin markedly reduced cell viability, blocked cell cycle progression and
      induced apoptosis of human NPC cells. In addition, curcumin activated ER stress
      associated proteins to participate in the apoptosis of human NPC cells. siRNA
      induced knockdown of GRP78 may be able to strengthen the toxic effects of
      curcumin through mediating the AKT signaling pathway. These findings indicated
      that downregulation of GRP78 promoted the therapeutic effects of curcumin on NPC
      cells. The present study identified a potential, novel therapeutic method for the
      treatment of NPC.

PMID- 30226564
TI  - Upregulation of miR-183-5p is responsible for the promotion of apoptosis and
      inhibition of the epithelial-mesenchymal transition, proliferation, invasion and
      migration of human endometrial cancer cells by downregulating Ezrin.
AB  - Endometrial cancer is a life-threatening malignancy that affects women all over
      the world, and it has an increasing incidence. MicroRNAs (miRNAs/miRs) have been
      reported to be involved in cellular activities in endometrial cancer. The present
      study aimed to examine the effects of miR-183-5p on the epithelial-mesenchymal
      transition (EMT), proliferation, invasion, migration and apoptosis of human
      endometrial cancer cells by targeting Ezrin. Primary endometrial cancer tissues
      and adjacent normal tissues were obtained for the investigation. The protein
      expression of Ezrin in tissues was detected by immunohistochemistry. The
      expression level of miR-183-5p and the mRNA and protein expression levels of
      Ezrin and EMT-associated genes were determined by reverse transcription
      quantitative polymerase chain reaction and western blot analyses. Endometrial
      cancer cells were treated with miR-183-5p inhibitors, small interfering RNA
      targeting Ezrin or miR-183-5p inhibitors. Cell proliferation, cell cycle,
      apoptosis, migration and invasion were then evaluated using an MTT assay, flow
      cytometry, scratch test and Transwell assay, respectively. Compared with normal
      adjacent tissues, the expression of miR-183-5p was decreased in endometrial
      cancer tissues, and the expression of Ezrin was significantly increased in
      endometrial cancer tissues. The protein expression of Ezrin was correlated with
      the severity and poor prognosis of endometrial cancer. Notably, the target
      prediction program and the luciferase reporter gene assay confirmed that miR-183
      5p targeted and negatively regulated the expression of Ezrin. In vivo experiments
      revealed that the increased expression of miR-183-5p and decreased expression of
      Ezrin inhibited EMT, cell proliferation, migration and invasion, but promoted
      cell apoptosis in Ishikawa cells. These results suggested that the upregulated
      expression of miR-183-5p promoted apoptosis and suppressed the EMT,
      proliferation, invasion and migration of human endometrial cancer cells by
      downregulating Ezrin.

PMID- 30226565
TI  - Ultraviolet light-induced gasdermin C expression is mediated via
      TRPV1/calcium/calcineurin/NFATc1 signaling.
AB  - Gasdermin (GSDM)-C is a member of the GSDM gene family and is expressed in the
      epithelial cells of various tissue types, including skin. GSDMC expression is
      induced by ultraviolet (UV) irradiation and contributes to UV-induced matrix
      metalloproteinase 1 expression in human skin keratinocytes. However, how UV
      irradiation induces GSDMC expression remains unclear. The present study aimed to
      investigate the role of transient receptor potential cation channel subfamily V
      member 1 (TRPV1) and a calcium/calcineurin-signaling pathway in UV-induced GSDMC
      expression in human skin keratinocytes. Suppression of TRPV1 activity by
      treatment with the TRPV1 antagonists capsazepine and ruthenium red significantly
      reduced UV-induced GSDMC expression, whereas direct activation of TRPV1 by
      capsaicin, a TRPV1 agonist, increased GSDMC expression. The results demonstrated
      that extracellular calcium and calcineurin activity may be necessary for UV
      induced GSDMC expression in HaCaT cells. In addition, UV-induced GSDMC expression
      was either decreased or increased following knockdown or overexpression of
      nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), respectively. These
      data suggested that TRPV1 may serve an important role in the induction of GSDMC
      expression by UV and that UV-induced GSDMC expression may be mediated via a
      calcium/calcineurin/NFATc1 pathway.

PMID- 30226567
TI  - Macrophage migration inhibitory factor serves a pivotal role in the regulation of
      radiation-induced cardiac senescencethrough rebalancing the microRNA-34a/sirtuin
      1 signaling pathway.
AB  - Radiotherapy significantly increases survival innumerous cancer patients,
      although it may have delayed adverse effects, including significant short- and
      long-term effects on cardiovascular function, leading to significant morbidity
      and mortality. However, the mechanisms underlying these effects remain unclear.
      Cardiomyocyte senescence contributes to cardiovascular disease via impaired
      cardiac function. MicroRNA-34a (miR-34a) is a senescence-associated miR involved
      in the pathology of cardiovascular diseases, while macrophage migration
      inhibitory factor (MIF) is a cardioprotective cytokine with an important role in
      cardiovascular diseases. The present study aimed to determine whether MIF has a
      cytoprotective effect in cardiomyocytes exposed to radiation through modulating
      miR-34a. Human cardiomyocytes (HCMs) were incubated with MIF and then exposed to
      radiation. Cellular proliferation was measured using a Cell Counting Kit-8, while
      cellular senescence was evaluated based on the senescence-associated beta
      galactosidase activity and the gene expression levels of cyclin-dependent kinase
      inhibitor 1a (Cdkn1a) and Cdkn2c. Oxidative stress was evaluated by measuring the
      generation of reactive oxygen species and malondialdehyde, as well as the
      expression of antioxidant genes. In addition, HCMs were treated with small
      interfering RNA against sirtuin 1 (SIRT1) to examine the role of this gene in MIF
      associated rejuvenation following radiation-associated senescence. miR-34a was
      significantly increased in HCMs exposed to radiation, while MIF inhibited
      senescence by suppressing miR-34a. SIRT1 was identified as a target gene of miR
      34a, mediating the anti-senescence effect induced by MIF. Furthermore, MIF
      rejuvenation involved rebalancing the oxidation process disturbed by radiation.
      These results provided direct evidence that inhibition of miR-34a by MIF
      protected against radiation-induced cardiomyocyte senescence via targeting SIRT1.
      Inhibition of miR-34a by MIF may thus be a novel strategy for combating cardiac
      radiation-associated damage.

PMID- 30226566
TI  - Identification of 13 novel susceptibility loci for early-onset myocardial
      infarction, hypertension, or chronic kidney disease.
AB  - Early-onset cardiovascular and renal diseases have a strong genetic component. In
      the present study, exome-wide association studies (EWASs) were performed to
      identify genetic variants that confer susceptibility to early-onset myocardial
      infarction (MI), hypertension, or chronic kidney disease (CKD) in Japanese
      individuals. A total of 8,093 individuals aged <=65 years was enrolled in the
      study. The EWASs for MI, hypertension, and CKD were performed in 6,926 subjects
      (1,152 cases, 5,774 controls), 8,080 subjects (3,444 cases, 4,636 controls), and
      2,556 subjects (1,051 cases, 1,505 controls), respectively. Genotyping of single
      nucleotide polymorphisms (SNPs) was performed with Illumina Human Exome-12 DNA
      Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The associations of
      allele frequencies for 31,245, 31,276, or 31,514 SNPs that passed quality control
      to MI, hypertension, and CKD, respectively, was examined with Fisher's exact
      test. Bonferroni's correction for statistical significance of association was
      applied to compensate for multiple comparisons of genotypes with MI,
      hypertension, or CKD. The EWASs of allele frequencies revealed that 25, 11, and
      11 SNPs were significantly associated with MI (P<1.60x10-6), hypertension
      (P<1.60x10-6), or CKD (P<1.59x10-6), respectively. Multivariable logistic
      regression analysis with adjustment for covariates showed that all 25, 11, and 11
      SNPs were significantly associated with MI (P<0.0005), hypertension (P<0.0011),
      or CKD (P<0.0011), respectively. On examination of the results from previous
      genome-wide association studies and linkage disequilibrium of the identified
      SNPs, 11 loci (TMOD4, COL6A3, ADGRL3-CXCL8-MARCH1, OR52E4, TCHP-GIT2, CCDC63,
      12q24.1, OAS3, PLCB2-VPS33B, GOSR2, ZNF77), six loci (MOB3C-TMOD4, COL6A3,
      COL6A5, CXCL8-MARCH1, NFKBIL1-6p21.3-NCR3, PLCB2-VPS33B), and seven loci (MOB3C
      TMOD4, COL6A3, COL6A5, ADGRL3-CXCL8-MARCH1, MUC17, PLCB2-VPS33B, ZNF77) were
      identified as novel loci significantly associated with MI, hypertension, and CKD,
      respectively. Furthermore, six genes (TMOD4, COL6A3, CXCL8, MARCH1, PLCB2,
      VPS33B) were significantly associated with MI, hypertension and CKD; two genes
      (ADGRL3, ZNF77) with MI and CKD; and two genes (COL6A5, MOB3C) with hypertension
      and CKD. Therefore, 13 novel loci (MOB3C-TMOD4, COL6A3, ADGRL3-CXCL8-MARCH1,
      OR52E4, TCHP-GIT2, CCDC63, 12q24.1, OAS3, PLCB2-VPS33B, ZNF77, COL6A5, NFKBIL1
      NCR3, MUC17) were identified that confer susceptibility to early-onset MI,
      hypertension, or CKD. The determination of genotypes for the SNPs at these loci
      may provide informative for assessment of the genetic risk for MI, hypertension,
      or CKD.

PMID- 30226568
TI  - Involvement of brain-derived neurotrophic factor in exercise-induced
      cardioprotection of post-myocardial infarction rats.
AB  - Exercise induces a number of benefits, including angiogenesis in post-myocardial
      infarction (MI); however, the underlying mechanisms have not been fully
      clarified. Neurotrophic brain-derived neurotrophic factor (BDNF) serves a
      protective role in certain adult cardiac diseases through its specific receptor,
      BDNF/NT-3 growth factors receptor (TrkB). The present study explored the
      mechanisms by which exercise improves cardiac function, with a focus on the
      involvement of the BDNF/TrkB axis. MI rats were assigned to Sham, sedentary,
      exercise, exercise with K252a (a TrkB inhibitor), and exercise with NG-nitro-L
      arginine methyl ester (L-NAME) groups. The exercise group was subjected to 8
      weeks of treadmill running. The results demonstrated that the rats in the
      exercise group exhibited increased myocardial angiogenesis and improved cardiac
      function, which was attenuated by K252a. Exercise induced activation of the
      BDNF/TrkB axis in the ischaemic myocardium and increased serum BDNF levels were
      abated by exposure to L-NAME. Improvements in angiogenesis and left ventricular
      function exhibited a positive association, with changes in serum BDNF. In the in
      vitro experiments, human umbilical vein endothelial cells were exposed to shear
      stress (SS) of 12 dyn/cm2 to mimic the effects of exercise training on vascular
      tissue. An increased tube-forming capacity, and a nitric oxide (NO)-dependent
      prolonged activation of the BDNF/TrkB-full-length axis over 12 h, but not the
      TrkB-truncated axis, was observed. The SS-related angiogenic response was
      attenuated by TrkB inhibition. Overall, these results demonstrate that exercise
      confers certain aspects of its cardioprotective effects through the activation of
      the BDNF/TrkB axis in an NO-dependent manner, a process in which fluid-induced SS
      may serve a crucial role.

PMID- 30226569
TI  - ISL1 promotes cancer progression and inhibits cisplatin sensitivity in triple
      negative breast cancer cells.
AB  - Triple-negative breast cancer (TNBC) is a type of breast cancer that is
      characterized by the lack of expression of estrogen and progesterone receptors,
      and epidermal growth factor receptor 2. Therefore, there is an absence of a
      specific target for effective therapy in TNBC. Cisplatin is usually employed as a
      first-line chemotherapy agent for patients with TNBC. However, resistance remains
      an obstacle for cisplatin-based chemotherapy, due to its elusive underlying
      mechanism. Previously, abnormal expression of Islet 1 (ISL1) was demonstrated to
      be closely associated with cancer development and progression. The present study
      revealed that (ISL1) was significantly upregulated in TNBC tissues in comparison
      with adjacent normal tissues. Overexpression of ISL1 markedly promoted the
      proliferation and invasion of the TNBC MDA-MB-231 and MDA-MB-468 cell lines,
      while knockdown of ISL1 inhibited cell invasion and proliferation in these cell
      lines. In addition, overexpression of ISL1 reversed cisplatin-induced cell
      apoptosis, while knockdown of ISL1 enhanced apoptosis following cisplatin
      treatment in MDA-MB-231 and MDA-MB-468 cells. Furthermore, the levels of the anti
      apoptotic proteins, phosphorylated-protein kinase B and B-cell lymphoma-2 (Bcl
      2), were significantly decreased, while the levels of the pro-apoptotic protein
      Bcl-2-associated X protein were remarkably increased in response to cisplatin
      treatment. The present study revealed that ISL1 overexpression reversed the
      protein expression profile of p-Akt, Bcl-2 and Bax, while ISL1 knockdown promoted
      cell apoptosis. Therefore, the data of the present study demonstrated that ISL1
      contributes to TNBC progression and reverses cell sensitivity towards cisplatin
      in TNBC cells, suggesting that ISL1 is a potential therapeutic target for the
      treatment of TNBC.

PMID- 30226570
TI  - alpha-1,3-Fucosyltransferase-VII siRNA inhibits the expression of SLex and
      hepatocarcinoma cell proliferation.
AB  - The increased expression of sialyl-Lewisx (SLex) epitope on the surface of tumor
      cells has been known for decades. However, genetic manipulation of the expression
      of SLex and the role of SLex in cancer cell proliferation remains to be fully
      elucidated. The present study suggested that the monoclonal antibody of SLex
      (KM93) significantly inhibited the proliferation of human hepatocarcinoma (HCC)
      cells. The expression levels of three sialyl-Lewis oligosaccharide antigens,
      SLex, SLea and dimeric SLex (SDLex), were determined on the cell surface of the
      MHCC97 human HCC cell line. The expression of SLex was markedly higher in MHCC97
      cells than in normal liver cells. The expression of SDLex was also relatively
      high, however, no significant difference was observed between normal liver cells
      and HCC cells. The expression of SLea was only detected in trace quantities.
      Fucosyltransferase (FUT) is the key enzyme of the fucosylation step in the
      biosynthesis of sialyl-Lewis oligosaccharide antigens. Therefore, the present
      study investigated the expression of FUTs. It was found that the mRNA and protein
      expression levels of FUT7 were high in the MHCC97 HCC cell line compared with
      levels in normal liver cells. FUT6 was also expressed at a high level, although
      the difference was not statistically significant between MHCC97 cells and normal
      liver cells. No expression of FUT3 was detected. The results were consistent with
      the change insialyl-Lewis antigens. The effects of FUT7 small interfering (si)RNA
      transfection on the expression of FUT7, expression of SLex and MHCC97 cell
      proliferation were also examined. Following FUT7 siRNA transfection, the
      expression of FUT7 was markedly downregulated, as determined by western blot and
      reverse transcription-quantitative polymerase chain reaction methods. The results
      from flow cytometry showed that the synthesis of SLex was also inhibited, which
      was consistent with the downregulated expression of FUT7. MHCC97 cell
      proliferation was also significantly inhibited following FUT7 siRNA transfection,
      which was correlated with suppression of the S-phase in cell cycle progression.
      By using inhibitors of various signaling pathways, it was found that the
      knockdown of FUT7 inhibited the activation of phospholipase Cgamma (PLCgamma) by
      inhibiting the translocation and phosphorylation of PLCgamma. In conclusion, the
      results suggested that FUT7 has animportant functional role in human HCC cell
      proliferation by controlling cell cycle progression via the
      PLCgamma/extracellular signal-regulated kinase signaling pathway. The inhibition
      of SLex and FUT7 siRNA transfection may provide a novel therapeutic methodology
      to treat tumors that express SLex glycoconjugates.

PMID- 30226572
TI  - Comprehensive literature data-mining analysis reveals a broad genetic network
      functionally associated with autism spectrum disorder.
AB  - Previous studies have indicated that genetic factors are the predominate cause of
      Autism spectrum disorder (ASD). Nevertheless, to the best of our knowledge, to
      date no systematic study has summarized these data and provided an objective,
      complete list of genes with demonstrated associations with ASD. The present study
      included a literature data mining analysis of >2,064 articles including
      publications from January 2000 to April 2016, which identified 488 ASD target
      genes. Gene set enrichment analysis (GSEA), sub-network enrichment analysis
      (SNEA) and network connectivity analysis (NCA) were conducted to assess the
      functional profile and pathogenic significance of these genes. A total of 2
      literature metrics were proposed to prioritize the curated ASD genes with
      specific significance. This approach resulted in the development of an ASD
      genetic database. Subsequent analysis indicated that 391 of the 488 genes were
      enriched in 97 biological pathways (P<1x10-8), demonstrating significant
      functional associations with each other. The majority of these curated ASD genes
      also serve significant roles in the pathogenesis of other neuropsychiatric
      disorders. These results suggest that the genetic causes of ASD are within a
      large network composed of functionally-associated genes. The genetic database,
      together with the metric scores developed in the present study, provides a basis
      for future biological/genetic modeling in the field.

PMID- 30226571
TI  - 3,5-Di-C-beta-D-glucopyranosyl phloroacetophenone, a major component of Melicope
      ptelefolia, suppresses fibroblast activation and alleviates arthritis in a mouse
      model: Potential therapeutics for rheumatoid arthritis.
AB  - Melicope ptelefolia has been traditionally used to treat rheumatism and fever.
      The present study aimed to investigate the therapeutic effect of 3,5-di-C-beta-D
      glucopyranosyl phloroacetophenone (betaGP), a main component of M. ptelefolia, on
      rheumatoid arthritis (RA). A model of collagen-induced arthritis (CIA) was
      established in mice using the RAW 264.7 murine macrophage cell line and mouse
      embryonic fibroblasts (MEFs). The clinical scores of arthritis, swelling,
      histopathological findings, and micro-computed tomography in CIA mouse paws were
      assessed. The levels of anti-type II collagen antibody and cytokines were
      determined in the plasma and cell culture supernatant, respectively. Protein and
      gene expression levels were analyzed by western blot and reverse transcription
      quantitative polymerase chain reaction analyses. betaGP significantly decreased
      the gross arthritic scores of CIA mice and joint swelling, and decreased
      articular inflammation, cartilage degradation and bone erosion. However, betaGP
      did not exert any effect on anti-type II collagen immunoglobulin G plasma levels
      or inflammatory cytokine expression in macrophages. betaGP significantly
      suppressed the expression of interleukin-6 and leukemia inhibitory factor and
      decreased the phosphorylation of signal transducer and activator of transcription
      3, and expression of receptor activator of nuclear factor-kappaB ligand in tumor
      necrosis factor-alpha-stimulated MEFs and in CIA mouse paws. Osteoclast-related
      gene expression was significantly reduced in CIA mouse paws. Taken together,
      betaGP suppressed the development of RA by regulating the activation of synovial
      fibroblasts.

PMID- 30226573
TI  - Systematic analysis of hsa-miR-363 gene overexpression pattern in endometrial
      stromal cells.
AB  - Endometriosis is a benign disease, but has invasion and metastasis
      characteristics similar to malignant tumors. Clinically, it is a difficult
      problem of gynecological clinical treatment for its high recurrence rate. It has
      been confirmed that miR-363 was downregulated in endometriosis tissues and miR
      363 overexpression inhibited the invasion ability of endometrial stromal cells
      (ESCs). In order to explore the potential mechanism of miR-363-reduced ESC
      migration and invasion progression, we sought to demonstrate the targeted mRNA
      expression levels of miR-363 through microarray, and performed cluster analysis
      to identify potential functions of these targeted genes in ESCs. The wound
      migration assay showed that there was an observable trend of cell migration
      potential decrease after transfection with hsa-miR-363. The qRT-PCR result showed
      that compared to miR-363 negative control cell group, miR-363 was upregulated
      3,264.58-fold after miR-363 lentiviral transfection in miR-363 mimics group. The
      microarray data showed that compared to ESCs miR-363 negative control cell group,
      249 genes were upregulated in ESCs miR-363 mimics cells group, and 139 genes were
      downregulated. Gene Ontology analysis and the pathway analysis data demonstrated
      that these target genes are mainly involved in cell migration, cell adhesion and
      invasion, proliferation, apoptosis, alteration of endometrial cells and some
      related signaling pathways. Our study explored the gene expression pattern after
      miR-363 overexpression, which could expand the insights into the miR-363 function
      and molecular mechanisms in endometriosis.

PMID- 30226574
TI  - Cardioprotective effects and underlying mechanism of Radix Salvia miltiorrhiza
      and Lignum Dalbergia odorifera in a pig chronic myocardial ischemia model.
AB  - Traditional Chinese medicines, including Radix Salvia miltiorrhiza (SM) and
      Lignum Dalbergia odorifera (DO) extracts, have historically been used to treat
      myocardial ischemia and other cardiovascular diseases. The volatile oil of DO
      (DOO) is one of the main components of DO. The aim of the present study was to
      assess the cardioprotective effects and possible underlying mechanisms of SM-DOO
      in pigs with ameroid constriction-induced chronic myocardial ischemia. An ameroid
      constrictor was placed around the left anterior descending coronary artery of
      pigs to induce chronic myocardial ischemia. At weeks 2, 6 and 8, myocardial
      injury markers and blood gas levels were detected. At week 8, coronary
      angiography, echocardiography and hemodynamics analysis were performed to
      evaluate myocardial function. Following sacrifice, myocardial tissue was
      collected and subjected to morphological, histopathological and apoptosis assays.
      Western blotting was used to detect the protein expression of Bcl-2 associated X
      (Bax), Bcl-2, Akt, phosphorylated (p)-Akt, glycogen synthase kinase (GSK)-3beta
      and p-GSK-3beta. It was revealed that SM-DOO treatment following chronic
      myocardial ischemia significantly downregulated the expression of myocardial
      injury markers, ameliorated myocardial oxygen consumption, increased
      collateralization, reduced regional cardiac dysfunction and limited the extent of
      myocardial damage. Furthermore, the results of an apoptosis assay revealed that
      the apoptosis rate was decreased, the expression of Bax decreased and Bcl-2
      increased, and the ratio of Bcl-2/Bax was increased. Further experiments
      indicated that treatment with SM-DOO increased the phosphorylation of Akt and GSK
      3beta. These findings suggest that SM-DOO treatment ameliorates myocardial injury
      in a chronic myocardial ischemia model, and that the underlying mechanisms
      responsible may be associated with the activation of the Akt/GSK-3beta signal
      pathway. Thus, experimental evidence that SM-DOO may be an effective drug for the
      prevention and treatment of chronic myocardial ischemia in clinical applications
      has been provided.

PMID- 30226575
TI  - CDCA3 mediates p21-dependent proliferation by regulating E2F1 expression in
      colorectal cancer.
AB  - Dysregulated cell cycle progression serves a crucial role in tumor development.
      Cell division cycle-associated 3 (CDCA3) is considered a trigger of mitotic
      entry; it is an important part of the S phase kinase-associated protein
      1/Cullin/F-box ubiquitin ligase complex and mediates the destruction of mitosis
      inhibitory kinase wee1. However, little is known about the role of CDCA3 in
      cancer, particularly colorectal cancer (CRC). The present study aimed to explore
      the biological and clinical significance of CDCA3 in CRC growth and progression.
      CDCA3 expression was significantly associated with tumor progression and poor
      survival. Overexpression of CDCA3 increased proliferation in LoVo CRC cells,
      whereas CDCA3 knockdown in SW480 CRC cells led to decreased proliferation, in
      vitro and in vivo. Further mechanistic investigations demonstrated that reduced
      CDCA3 expression resulted in G1/S phase transition arrest, which was attributed
      to a significant accumulation of p21 in SW480 cells; conversely, increased CDCA3
      expression promoted G1/S phase transition through decreased p21 accumulation in
      LoVo cells. It was also demonstrated that CDCA3 was able to regulate the
      expression of transcription factor E2F1, thereby repressing p21 expression. Taken
      together, these results suggested that overexpression of CDCA3 may serve a
      crucial role in tumor malignant potential and that CDCA3 may be used as a
      prognostic factor and a potential therapeutic target in CRC.

PMID- 30226576
TI  - Long non-coding RNA HOTTIP promotes renal cell carcinoma progression through the
      regulation of the miR-615/IGF-2 pathway.
AB  - Emerging evidence has indicated that long non-coding RNA (lncRNA) HOXA transcript
      at the distal tip (HOTTIP) regulates cell growth, differentiation, apoptosis and
      cancer progression. However, the expression and function of HOTTIP in the
      progression of renal cell carcinoma (RCC) remain largely unknown. In this study,
      we investigated the role of the lncRNA HOTTIP in RCC. The expression levels of
      HOTTIP in RCC tissues and cell lines were determined by RT-qPCR. The association
      between HOTTIP expression and clinicopathological characteristics and prognosis
      was analyzed in patients with RCC from the TCGA database. Loss-of- function
      assays were designed and conducted to verify the oncogenic function of HOTTIP in
      RCC progression. Luciferase assay was performed to explore the mechanisms of the
      miRNA-lncRNA sponge. The results revealed that HOTTIP expression was upregulated
      in RCC. An increased HOTTIP expression in RCC was associated with a larger tumor
      size and a higher clinical stage, lymph node metastasis and vascular invasion.
      Additionally, patients RCC with a high HOTTIP expression had a significantly
      shorter overall survival (OS) and disease-free survival (DFS). HOTTIP knockdown
      significantly inhibited cell proliferation, migration and invasion, and increased
      the apoptosis of RCC cells in vitro. Mechanistic analyses revealed that HOTTIP
      functioned as a competing endogenous RNA (ceRNA) for hsa-miR-615-3p, and led to
      the derepression of its endogenous target, insulin-like growth factor-2 (IGF-2),
      which is a protein hormone that exerts a stimulatory effect on tumor cell growth.
      miR-615 inhibition reversed the suppressive effects of HOTTIP knockdown on RCC
      cell progression. HOTTIP regulated IGF-2 expression in a miR-615-dependent manner
      in RCC cells. In addition, IGF-2 expression was significantly upregulated in the
      RCC specimens and a positive association between the expression of HOTTIP and IGF
      2 in RCC tissues was detected. The effect of HOTTIP was abolished by the siRNA
      mediated silencing of IGF-2 in RCC cells. On the whole, this study demonstrates,
      for the first time, at least to the best of our knowledge, that the HOTTIP/miR
      615/IGF-2 axis plays an important role in RCC progression and potentially
      contributes to the improvement of RCC diagnosis and therapy.

PMID- 30226577
TI  - Overexpression of SENP1 reduces the stemness capacity of osteosarcoma stem cells
      and increases their sensitivity to HSVtk/GCV.
AB  - Osteosarcoma stem cells are able to escape treatment with conventional
      chemotherapeutic drugs, as the majority of them are in a quiescent state. Recent
      reports have suggested that small ubiquitin-like modifiers (SUMOs) serve
      important roles in the maintenance of cancer stem cell stemness. Therefore, a
      potential strategy to increase the effectiveness of chemotherapeutic agents is to
      interfere with SUMO modification of proteins associated with the maintenance of
      stemness in osteosarcoma stem cells. The present study revealed a significant
      decrease in the expression of SUMO1 specific peptidase 1 (SENP1) in osteosarcoma
      tissues and osteosarcoma cell lines, and SENP1 expression was much lower in
      osteosarcoma stem cells than in non-cancer stem cells. Further experiments
      indicated that the low levels of SENP1 were essential for maintenance of stemness
      in osteosarcoma stem cells. Overexpression of SENP1 resulted in a marked decrease
      in the maintenance of stemness, but only slightly induced apoptosis of
      osteosarcoma cells, which is crucial to reduce the side effects of drugs on
      normal precursor cells. Finally, SENP1 overexpression led to a significant
      increase in the sensitivity of osteosarcoma stem cells to the herpes simplex
      virus 1 thymidine kinase gene in combination with ganciclovir in vitro and in
      vivo. In conclusion, the present study described a novel method to increase the
      sensitivity of osteosarcoma stem cells to chemotherapeutic drugs. Notably, this
      approach may significantly reduce the required dose of conventional
      chemotherapeutic drugs and reduce side effects.

PMID- 30226578
TI  - Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer
      cell proliferation and migration.
AB  - Accumulating evidence has revealed that the methylation of lysines on nonhistones
      by histone lysine methyltransferases (HMTs) is crucial for regulating tumo
      rigenesis and metastasis. However, whether the methy-lation of lysines on HMT
      complex components occurs and has functions in cancer progression is less well
      understood. WD repeat domain 5 (WDR5) is a core component of an HMT complex named
      mixed lineage leukemia (MLL)/Suppressor of Variegation, Enhancer of Zeste, and
      Trithorax 1 (SET1). In the present study, it was reported that lysines 207 and
      325 (K207 and K325, respectively) of WDR5 were monomethylated by SET-domain
      containing protein methyltransferase 6. Disrupting the methylation of K207/K325
      via a K207R/K325R double-site mutation attenuated the WDR5 promotion of breast
      cancer cell proliferation and migration. Methylation of K207/K325 on WDR5
      partially contributed to maintaining global histone tri-methylation of lysine 4
      on histone H3 levels, but did not affect MLL/SET1 complex assembly. These results
      further understanding of a potential post-translational modification of WDR5, and
      imply that the methylation of lysines on HMT complex components is crucial for
      regulating human carcinogenesis.

PMID- 30226579
TI  - Effects of microRNA-125b on multiple myeloma cell growth in vitro and in vivo.
AB  - Multiple myeloma (MM) is a heterogeneous disease with a poor prognosis. The
      expression of microRNA-125b (miR-125b), a novel oncomiR, is elevated in various
      cancer types. The present study found that the expression of miR-125b was
      increased in plasma samples from 35 patients with MM, compared with that in
      samples from 20 healthy controls, by performing real-time PCR. CCK-8 assay,
      migration and invasion assay showed that the downregulation of miR-125b inhibited
      cell proliferation and migration and reduced the levels of phosphorylated Akt,
      compared with those of the blank and negative control groups. Dual-Luciferase
      activity assay demonstrated that the tumor suppressor PH domain and leucine rich
      repeat protein phosphatase 2 (PHLPP2) was a target of miR-125b, which inhibited
      PHLPP2 and directly bound to the 3'untranslated region of PHLPP2, resulting in
      elevated Akt signaling. Furthermore, the expression of a miR-125b inhibitor in MM
      cells in a xenograft mouse model suppressed tumor growth. These results showed
      that the inhibition of miR-125b suppressed MM progression by inhibiting Akt
      signaling, and suggested that miR-125b may be a novel molecular therapeutic
      target for MM treatment.

PMID- 30226581
TI  - MicroRNA-145 inhibits migration and induces apoptosis in human non-small cell
      lung cancer cells through regulation of the EGFR/PI3K/AKT signaling pathway.
AB  - In the present study, the therapeutic effects and the underlying molecular
      mechanisms of microRNA (miR)-145 were investigated in non-small cell lung cancer
      (NSCLC) cells. Reverse transcription-quantitative polymerase chain reaction (RT
      qPCR) was performed to examine miR-145 expression. An MTT assay and flow
      cytometry were used to investigate cell proliferation and apoptosis,
      respectively. The protein expression of Bax, epidermal growth factor receptor
      (EGFR), phosphatidylinositol 3-kinase (PI3K) and phosphorylated-protein kinase B
      (AKT) was examined by western blot analysis. miR-145 expression was downregulated
      in patients with NSCLC who were treated with chemotherapy. The downregulation of
      miR-145 in A549 cells reduced lactate dehydrogenase (LDH) expression, apoptosis,
      caspase-3/-9 levels and Bax protein expression, while it increased cell
      proliferation. Upregulation of miR-145 in A459 cells increased LDH, apoptosis,
      caspase-3/-9 levels and Bax protein expression, while it inhibited cell
      proliferation. The EGFR/PI3K/AKT signaling pathway was suppressed by miR-145
      upregulation in A549 cells and induced by miR-145 downregulation. The EGFR
      inhibitor suppressed the EGFR/PI3K/AKT signaling pathway and increased the
      anticancer effects of miR-145 upregulation in A549 cells. The PI3K inhibitor
      suppressed the PI3K/AKT signaling pathway and reversed the anticancer effects of
      miR-145 upregulation in A549 cells. In conclusion, the present study demonstrated
      that miR-145 regulates the EGFR/PI3K/AKT signaling pathway in patients with
      NSCLC.

PMID- 30226580
TI  - Dynamic influence of Rhein lysinate on HeLa cells.
AB  - In a previous study, it was demonstrated that Rhein lysinate (RHL) inhibited HeLa
      cell proliferation via a specific mechanism. The aim of the present study was to
      clarify the mechanism of RHL by investigating its effect on mitochondrial damage
      and cell apoptosis. The results indicated that RHL inhibited cell growth and
      proliferation in HeLa cells. HeLa cells treated with RHL developed extensive
      vacuolization in a dose- and time-dependent manner. Ultrastructure analysis using
      transmission electron microscopy revealed that the vacuoles observed were damaged
      mitochondria and endoplasmic reticulum. The effects of RHL on mitochondria were
      further confirmed by a decrease in mitochondrial membrane potential and increased
      generation of reactive oxygen species. The mitochondrial proteome was analyzed,
      and the results demonstrated that the expression of the cytoskeletal protein
      keratin and dermal papilla derived protein 12 (associated with the oxidation
      reduction process), which are associated with mitochondrial structure and
      function, were decreased compared with the untreated control group. Hoechst
      staining, flow cytometry and western blotting also revealed that apoptosis was
      induced at 24 h following RHL treatment. These results confirm that RHL toxicity
      in HeLa cells is a dynamic process. Vacuolar degeneration appeared in HeLa cells
      treated with 160 umol/l RHL during the first 6 h and with the extension of RHL
      treatment, cell apoptosis was presented at ~24 h in HeLa cells.

PMID- 30226582
TI  - ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2
      and GSK-3alpha/beta signaling in pancreatic cancer.
AB  - Rho guanine nucleotide exchange factor 4 (ARHGEF4) is a guanine nucleotide
      exchange factor that is specific for Rac1 and Cdc42. The aim of the present study
      was to investigate the role of ARHGEF4 in the motility and invasiveness of
      pancreatic cancer cells. Evaluation of an immunohistochemical staining of 102
      resected pancreatic cancer samples demonstrated that high ARHGEF4 expression was
      correlated with an independent predictor of worse overall survival in univariate
      and multivariate analyses. Immunofluorescence analyses and Matrigel invasion
      assays demonstrated that suppression of ARHGEF4 inhibited the formation of
      membrane protrusions, and in turn inhibited cell motility and invasion. A
      phosphoprotein array analysis demonstrated that knockdown of ARHGEF4 decreased
      phosphorylated extracellular signal-regulated kinase (ERK)1/2 and glycogen
      synthase kinase-3 (GSK-3)alpha/beta in pancreatic cancer cells, and ERK1/2 and
      GSK-3alpha/beta were associated with ARHGEF4-related motility and invasiveness
      through an increase in cell protrusions. These results suggested that ARHGEF4
      stimulates ERK1/2 and GSK-3alpha/beta, and provided evidence that ARHGEF4
      promotes cell motility and invasiveness. Inhibition of ARHGEF4 may be a novel
      approach to a targeted molecular therapy, as any such therapy would limit the
      motility and invasiveness of pancreatic cancer cells.

PMID- 30226583
TI  - Knockdown of pleiotrophin increases the risk of preeclampsia following vitrified
      thawed embryo transfer.
AB  - Preeclampsia (PE) in pregnancy is associated with vitrified-thawed embryo
      transfer. Pleiotrophin (PTN) is important in inflammation via its receptors. The
      aim of the present study was to determine the effect of PTN on the risk of PE
      following embryo transfer. An enzyme-linked immunosorbent assay was performed to
      determine the levels of tumor necrosis factor (TNF)-alpha and PTN in serum. The
      knockdown of PTN was conditionally induced by tamoxifen (tax) treatment. The tail
      cuff method and Bradford assay were used to monitor blood pressure and the level
      of urine protein, respectively. The expression patterns of PTN, receptor protein
      tyrosine phosphatase beta/zeta, (RPTPbeta/zeta), syndecan-1 (SDC1), syndecan-3
      (SDC3) and anaplastic lymphoma kinase (ALK) were determined by
      immunohistochemistry (IHC). Western blot analysis was performed to evaluate the
      expression level of PTN and its receptors. The risk of PE was elevated following
      embryo transfer in clinical and in the tax/PTN-/- group. It was found that the
      level of PTN increased when pregnancy progressed in normal conditions, however,
      the level of PTN was reduced in the PE mice. In addition, increases in TNF-alpha,
      blood pressure and urine protein were more marked in the PE mice that lacked PTN,
      compared with those in other PE mice. In addition, overlapping expression of PTN
      and its receptors in villous mesenchyme and fetal macrophages were identified
      using an IHC assay. However, the positive staining of PTN and its receptors was
      weaker or even absent in the PE mice. The protein level of RPTPbeta/zeta was
      lower in the PE mice that lacked PTN than that in the other PE mice. The
      knockdown of PTN increased the risk of PE following vitrified-thawed embryo
      transfer, in which its receptors, particularly RPTPbeta/zeta, may be involved.

PMID- 30226584
TI  - CRISPR/Cas9-mediated hypoxia inducible factor-1alpha knockout enhances the
      antitumor effect of transarterial embolization in hepatocellular carcinoma.
AB  - Transarterial embolization (TAE) is a palliative option commonly used for the
      treatment of advanced, unresectable hepatocellular carcinoma (HCC). However,
      patient prognosis in regards to overall survival has not improved with this
      method, mainly due to hypoxia-inducible factor-1alpha (HIF-1alpha)-induced
      angiogenesis and invasiveness. Thus, it is hypothesized that HIF-1alpha may be an
      ideal knockout target for the treatment of HCC in combination with TAE. Thus, in
      the present study, HIF-1alpha knockout was conducted in human liver cancer SMMC
      7721 cells and a xenograft HCC model was established using a lentivirus-mediated
      CRISPR/Cas system (LV-Cas) with small guide RNA-721 (LV-H721). Furthermore,
      hepatic artery ligation (HAL) was used to mimic human transarterial
      chemoembolization in mice. The results revealed that HIF-1alpha was highly
      expressed in both HCC patient tissues and SMMC-7721-induced tumor tissues. The
      HIF-1alpha knockout in SMMC-7721 cells significantly suppressed cell invasiveness
      and migration, and induced cell apoptosis under CoCl2-mimicking hypoxic
      conditions. Compared with the control groups, HAL + LV-H721 inhibited SMMC-7721
      tumor growth in orthotopic HCC and markedly prolonged the survival of HCC-bearing
      mice, which was accompanied by a lower CD31 expression (tumor angiogenesis) and
      increased apoptosis in the tumor cells. These findings demonstrated a valuable
      antitumor synergism in combining CRISPR/Cas9-mediated HIF-1alpha knockout with
      TAE in mice and highlighted the possibility that HIF-1alpha may be an effective
      therapeutic knockout target in combination with TAE for HCC treatment.

PMID- 30226585
TI  - B7-H3 on circulating epithelial tumor cells correlates with the proliferation
      marker, Ki-67, and may be associated with the aggressiveness of tumors in breast
      cancer patients.
AB  - Circulating epithelial tumor cells (CETCs) in peripheral blood are a prerequisite
      for the development of metastases. B7-H3 is an important immune checkpoint member
      of the B7 family and inhibits T-cell mediated antitumor immunity. Its expression
      is associated with a negative prognosis and a poor clinical outcome. Based on the
      clinical success of inhibitory immune checkpoint blockade, monoclonal antibodies
      (mAbs) against B7-H3 appear to be a promising therapeutic strategy. The
      proliferation biomarker, Ki-67, is used as a prognostic factor for breast cancer
      and reflects the proliferative potential of the tumor. In order to better
      understand the role of B7-H3 and Ki-67 in cancer development, in this study, we
      used a real-time biopsy for determining both biomarkers on CETCs in breast cancer
      patients. Blood from 50 patients suffering from breast cancer was analyzed for
      CETCs and the expression of B7-H3 and Ki-67 using the maintrac(r) method. B7-H3
      expression on CETCs was found in 82% of the patients. The frequency of B7-H3- and
      Ki-67-positive CETCs was significantly higher in patients who had received
      radiation therapy compared to patients who had not received irradiation. B7-H3
      positive CETCs seemed to be more aggressive as the percentage of B7-H3-positive
      CETCs correlated with the percentage of cells positive for the proliferation
      marker, Ki-67 (r=0.72 P<0.001). A significant association between the Ki-67 and
      B7-H3 expression level on the CETCs and nodal status was observed. On the whole,
      the findings of this study indicate that breast cancer patients have detectable
      CETCs with a high frequency of B7-H3 expression regardless of the stage of the
      disease. B7-H3 seems to be an important factor in immune evasion and may thus be
      a promising target for anticancer therapies. Radiation may lead to an
      upregulation of B7-H3 expression on CETCs, which could be a possible mechanism of
      acquired radio-resistance.

PMID- 30226586
TI  - Uncovering the pharmacological response of novel sesquiterpene derivatives that
      differentially alter gene expression and modulate the cell cycle in cancer cells.
AB  - The present study aimed to assess the pharmacological anticancer profile of three
      natural and five synthetic sesquiterpenes developed by total chemical synthesis.
      To this end, their properties at the cellular and molecular level were evaluated
      in a panel of normal and cancer cell lines. The results obtained by performing
      cytotoxicity assays and gene expression analysis by reverse transcription
      quantitative polymerase chain reaction showed that: i) Among the sesquiterpene
      derivatives analyzed, VDS58 exhibited a notable anticancer profile within
      attached (U-87 MG and MCF-7) and suspension (K562 and MEL-745) cancer cell
      cultures; however, U-87 MG cells were able to recover their proliferation
      capacity rapidly after 48 h of exposure; ii) gene expression profiling of U-87 MG
      cells, in contrast to K562 cells, showed a transient induction of cyclin
      dependent kinase inhibitor 1A (CDKN1) expression; iii) the expression levels of
      transforming growth factor beta1 (TGFB1) increased after 12 h of exposure of U-87
      MG cells to VDS58 and were maintained at this level throughout the treatment
      period; iv) in K562 cells exposed to VDS58, TGFB1 expression levels were
      upregulated for 48 h and decrease afterwards; and v) the re-addition of VDS58 in
      U-87 MG cultures pretreated with VDS58 resulted in a notable increase in the
      expression of caspases (CASP3 and CASP9), BCL2-associated agonist of cell death
      (BAD), cyclin D1, CDK6, CDKN1, MYC proto-oncogene bHLH transcription factor
      (MYC), TGFB1 and tumor suppressor protein p53. This upregulation persisted only
      for 24 h for the majority of genes, as afterwards, only the expression of TGFB1
      and MYC was maintained at high levels. Through bioinformatic pathway analysis of
      RNA-Seq data of parental U-87 MG and K562 cells, substantial variation was
      reported in the expression profiles of the genes involved in the regulation of
      the cell cycle. This was associated with the differential pharmacological
      profiles observed in the same cells exposed to VDS58. Overall, the data presented
      in this study provide novel insights into the molecular mechanisms of action of
      sesquiterpene derivatives by dysregulating the expression levels of genes
      associated with the cell cycle of cancer cells.

PMID- 30226587
TI  - Silencing the expression of MTDH increases the radiation sensitivity of SKOV3
      ovarian cancer cells and reduces their proliferation and metastasis.
AB  - Ovarian cancer has a high mortality rate among women worldwide. Radiotherapy is
      considered an effective method of ovarian cancer treatment, however,
      radioresistance presents a challenge. It is necessary to develop techniques that
      can increase radiosensitivity in ovarian cancer, and gene therapy is a promising
      option. The aim of the present study was to investigate the effects of metadherin
      (MTDH) silencing on the radiosensitivity of ovarian cancer. Ovarian cancer
      tissues (n=273) and normal ovarian tissues (n=277) were used, as were SKOV3
      ovarian cancer cells and the immortalized human ovarian epidermal HOSEpiC cell
      line. MTT, Transwell and wound-healing assays were performed to assess the
      proliferation, invasion and migration abilities of the SKOV3 cells. Colony
      forming assays and flow cytometry were applied to detect the radiosensitivity and
      apoptosis of the SKOV3 cells. Nude mouse xenograft models were established to
      evaluate the effect of MTDH gene silencing on tumor growth and the efficacy of
      radiotherapy. Ovarian cancer, in tissues and cells, was demonstrated to have a
      high level of MTDH. Additionally, MTDH silencing was found to significantly
      inhibit proliferation, migration and invasion, and induce apoptosis in SKOV3
      cells, and it was suggested that MTDH depletion significantly increased the
      sensitivity of the SKOV3 cells to X-ray radiation. MTDH silencing enhanced
      radiosensitivity and delayed tumor growth in the nude mouse xenograft model.
      Collectively, the results obtained in the present study suggest the potential
      role of MTDH silencing as a technique for ameliorating radioresistance in ovarian
      cancer. The present study provides a promising experimental basis for the
      improvement of ovarian cancer radiotherapy treatment.

PMID- 30226588
TI  - Upregulation of liver kinase B1 predicts poor prognosis in hepatocellular
      carcinoma.
AB  - The majority of studies report that liver kinase B1 (LKB1) acts as a tumor
      suppressor by inhibiting cell proliferation and metastasis. The present study
      investigated the expression pattern of LKB1 in 2 cohorts of paired hepatocellular
      carcinoma (HCC) and analogous non-cancerous tissues (ANT). The results indicated
      that LKB1 was upregulated in HCC vs. ANT tissues, and that high expression of
      LKB1 was associated with a higher number of tumor foci, larger tumor size, poorer
      tumor differentiation, Edmondson-Steiner grade, Barcelona Clinic Liver Cancer
      grade and tumor-node-metastasis stage. Furthermore, high LKB1 expression was
      associated with poor overall survival (OS), shorter disease-free survival and
      early recurrence. Univariate and multivariate analyses demonstrated that high
      LKB1 expression may serve as an independent prognostic marker for OS, but not for
      recurrence. In addition, knockdown of LKB1 expression in HCC cell lines inhibited
      cell proliferation and subcutaneous tumor growth by promoting cell apoptosis.
      Therefore, the findings of the present study suggest a proto-oncogenic role of
      LKB1 in HCC.

PMID- 30226589
TI  - miR-17-92 functions as an oncogene and modulates NF-kappaB signaling by targeting
      TRAF3 in MGC-803 human gastric cancer cells.
AB  - The miR-17-92 cluster plays either an oncogenic or anti-oncogenic role in cancer
      progression in diverse human cancers. However, the underlying mechanisms of the
      miR-17-92 cluster in gastric cancer have not yet been fully elucidated. In this
      study, the function of the miR-17-92 cluster in diverse aspects of MGC-803
      gastric cancer cells was systematically elucidated. The enforced introduction of
      the miR-17-92 cluster into the MGC-803 cells significantly promoted cell growth
      due to the increased cellular proliferation and decreased cellular apoptosis,
      which were detected by CCK-8, cell viability and TUNEL assays. Moreover, the
      results of western blot analyses revealed that the activated protein kinase B
      (AKT), extracellular-signal-regulated kinase (ERK) and nuclear factor (NF-kappaB)
      signaling pathways were activated in these processes. Moreover, the
      overexpression of the miR-17-92 cluster markedly enhanced the migratory and
      invasive abilities of the MGC-803 cells, which was associated with the occurrence
      of epithelial-mesenchymal transition (EMT). Tumor necrosis factor receptor
      associated factor 3 (TRAF3), which negatively regulates the NF-kappaB signaling
      pathway, was identified as a direct target of miR-17-92. Furthermore, TRAF3
      silencing enhanced the oncogenic functions of the miR-17-92 cluster in the MGC
      803 cells, including the increased cellular proliferation, migration and
      invasion. Moreover, immunohistochemical staining and survival analyses of a
      gastric cancer tissue microarray revealed that TRAF3 functioned as a tumor
      suppressor in gastric cancer. Taken together, the findings of this study provide
      new insight into the specific biological functions of the miR-17-92 cluster in
      gastric cancer progression by directly targeting TRAF3.

PMID- 30226590
TI  - Preclinical investigation of folate receptor-targeted nanoparticles for
      photodynamic therapy of malignant pleural mesothelioma.
AB  - Photodynamic therapy (PDT) following lung-sparing extended pleurectomy for
      malignant pleural mesothelioma (MPM) has been investigated as a potential means
      to kill residual microscopic cells. High expression levels of folate receptor 1
      (FOLR1) have been reported in MPM; therefore, targeting FOLR1 has been considered
      a novel potential strategy. The present study developed FOLR1-targeting porphyrin
      lipid nanoparticles (folate-porphysomes, FP) for the treatment of PDT.
      Furthermore, inhibition of activated epidermal growth factor (EGFR)-associated
      survival pathways enhance PDT efficacy. In the present study, these approaches
      were combined; FP-based PDT was used together with an EGFR-tyrosine kinase
      inhibitor (EGFR-TKI). The frequency of FOLR1 and EGFR expression in MPM was
      analyzed using tissue microarrays. Confocal microscopy and a cell viability assay
      were performed to confirm the specificity of FOLR1-targeting cellular uptake and
      photocytotoxicity in vitro. In vivo fluorescence activation and therapeutic
      efficacy were subsequently examined. The effects of EGFR-TKI were also assessed
      in vitro. The in vivo combined antitumor effect of EGFR-TKI and FP-PDT was then
      evaluated. The results revealed that FOLR1 and EGFR were expressed in 79 and 89%
      of MPM samples, respectively. In addition, intracellular uptake of FP
      corresponded well with FOLR1 expression. When MPM cells were incubated with FP
      and then irradiated at 671 nm, there was significant in vitro cell death, which
      was inhibited in the presence of free folic acid, thus suggesting the specificity
      of FPs. FOLR1 targeting resulted in disassembly of the porphysomes and subsequent
      fluorescence activation in intrathoracic disseminated MPM tumors, as demonstrated
      by ex vivo tissue imaging. FP-PDT resulted in significant cellular damage and
      apoptosis in vivo. Furthermore, the combination of pretreatment with EGFR-TKI and
      FP-PDT induced a marked improvement of treatment responses. In conclusion, FP
      based PDT induced selective destruction of MPM cells based on FOLR1 targeting,
      and pretreatment with EGFR-TKI further enhanced the therapeutic response.

PMID- 30226591
TI  - Inhibition of atypical protein kinase C-iota effectively reduces the malignancy
      of prostate cancer cells by downregulating the NF-kappaB signaling cascade.
AB  - Prostate cancer (PC) is the most common type of cancer among men. Aggressive and
      metastatic PC results in life-threatening tumors, and represents one of the
      leading causes of mortality in men. Previous studies of atypical protein kinase C
      isoforms (aPKCs) have highlighted its role in the survival of cultured prostate
      cells via the nuclear factor (NF)-kappaB pathway. The present study showed that
      PKC-iota was overexpressed in PC samples collected from cancer patients but not
      in non-invasive prostate tissues, indicating PKC-iota as a possible prognostic
      biomarker for the progression of prostate carcinogenesis. Immunohistochemical
      staining further confirmed the association between PKC-iota and the prostate
      malignancy. The DU-145 and PC-3 PC cell lines, and the non-neoplastic RWPE-1
      prostatic epithelial cell line were cultured and treated with aPKC inhibitors 2
      acetyl-1,3-cyclopentanedione (ACPD) and 5-amino-1-(1R,2S,3S,4R)-2,3-dihydroxy-4
      methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1). Western blot data
      demonstrated that ICA-1 was an effective and specific inhibitor of PKC-iota and
      that ACPD inhibited PKC-iota and PKC-zeta. Furthermore, the two inhibitors
      significantly decreased malignant cell proliferation and induced apoptosis. The
      inhibitors showed no significant cytotoxicity towards the RWPE-1 cells, but
      exhibited cytostatic effects on the DU-145 and PC-3 cells prior to inducing
      apoptosis. The inhibition of aPKCs significantly reduced the translocation of NF
      kappaB to the nucleus. Furthermore, this inhibition promoted apoptosis, reduced
      signaling for cell survival, and reduced the proliferation of PC cells, whereas
      the normal prostate epithelial cells were relatively unaffected. Overall, the
      results suggested that PKC-iota and PKC-zeta are essential for the progression of
      PC, and that ACPD and ICA-1 can be effectively used as potential inhibitors in
      targeted therapy.

PMID- 30226592
TI  - Tamoxifen inhibits the proliferation of non-melanoma skin cancer cells by
      increasing intracellular calcium concentration.
AB  - Tamoxifen is an estrogen receptor (ER) antagonist used as first-line chemotherapy
      in breast cancer. Recent studies suggest that tamoxifen may be effective not only
      for ER-positive but also for ER-negative cancer cases. The aim of the present
      study was to investigate the antiproliferative effect of tamoxifen against human
      non-melanoma skin cancer cells. Tamoxifen inhibited the proliferation of the skin
      squamous cell carcinoma (SCC) cell lines A431, DJM-1 and HSC-1. A431 cells did
      not express ER-alpha or -beta, suggesting that tamoxifen may exert
      antiproliferative effects on skin SCC cells via a non-ER-mediated pathway.
      Tamoxifen increased the intracellular calcium concentration of skin SCC cells,
      and this increase in intracellular calcium concentration by calcium ionophore
      A23187 suppressed the proliferation of skin SCC cells. These data indicate that
      tamoxifen inhibited the proliferation of human skin SCC cells via increasing
      intracellular calcium concentration. Voltage-gated calcium channels and non
      selective cation channels are involved in the increase in intracellular calcium
      concentration induced by tamoxifen. The broad-spectrum protein kinase C (PKC)
      inhibitor phloretin significantly attenuated the antiproliferative effect of
      tamoxifen on skin SCC cells. From these data, it may be concluded that tamoxifen
      inhibits the proliferation of skin SCC cells by induction of extracellular
      calcium influx via calcium channels in the plasma membrane and by subsequent
      activation of PKC.

PMID- 30226593
TI  - Effects of 3-butenyl isothiocyanate on phenotypically different prostate cancer
      cells.
AB  - Isothiocyanates (ITCs) have gained increasing attention since they have been
      attributed the merits for the potential beneficial effects of cruciferous
      vegetable dietary consumption on cancer. The aim of the present study was to
      determine the cytotoxic effects of 3-butenyl ITC (3-BI) on prostate cancer (PC)
      cells under in vitro conditions. Two androgen-insensitive human PC cell lines, PC
      3 and DU145, were assayed. Cells were cultured in the presence of increasing
      concentrations of 3-BI (5, 10, 30 and 50 uM) in the absence or presence of the
      chemotherapeutic drug docetaxel (DOCE) (1 and 2 nM). The cytotoxic effects of
      these compounds were analyzed using the trypan blue exclusion assay at 24, 48 and
      72 h. Apoptosis and migration assays were also performed. The results showed that
      3-BI induced a dose-dependent cytotoxic effect on PC-3 cells at 24, 48 and 72 h.
      These effects were significantly higher than those found with DOCE at 72 h of
      culture. Moreover, 3-BI also potentiated the effects of DOCE in a dose-dependent
      manner. Additionally, 3-BI showed inhibition of the migration of PC-3 cells.
      Nevertheless, 3-BI was not effective in the DU145 PC cell line. These results
      show a promising role for the 3-BI compound as a co-adjuvant agent in DOCE-based
      therapy in certain types of PC.

PMID- 30226594
TI  - KIF14 promotes cell proliferation via activation of Akt and is directly targeted
      by miR-200c in colorectal cancer.
AB  - As a mitotic kinesin, kinesin family member 14 (KIF14) has been reported to serve
      oncogenic roles in a variety of malignancies; however, its functional role and
      regulatory mechanisms in colorectal cancer (CRC) remain unclear. In the present
      study, KIF14 was observed to be markedly overexpressed in CRC, and this
      upregulation was associated with tumor size and marker of proliferation Ki-67
      immunostaining scores. Gain- and loss-of-function experiments were applied to
      identify the function of KIF14 in CRC progression. In vitro and in vivo assays
      revealed that KIF14 promoted CRC cell proliferation and accelerated the cell
      cycle via activation of protein kinase B. In addition, the present study
      investigated the potential mechanisms underlying KIF14 overexpression in CRC.
      Bioinformatics analyses and validation experiments, including reverse
      transcription-quantitative polymerase chain reaction, western blotting and a Dual
      Luciferase reporter assay, demonstrated that, in addition to genomic
      amplification and transcriptional activation, KIF14 was regulated by microRNA
      (miR)-200c at the post-transcriptional level. Rescue experiments further
      demonstrated that decreased miR-200c expression could facilitate KIF14 to exert
      its pro-proliferative role. The expression of miR-200c was negatively correlated
      with KIF14 in CRC specimens. Collectively, the findings of the present study
      demonstrated the oncogenic role of KIF14 in colorectal tumorigenesis, and also
      revealed a complexity of regulatory mechanisms mediating KIF14 overexpression,
      which may provide insight for developing novel treatments for patients with CRC.

PMID- 30226595
TI  - Distinct phenotypes and 'bystander' effects of senescent tumour cells induced by
      docetaxel or immunomodulatory cytokines.
AB  - Cellular senescence is the process of the permanent proliferative arrest of cells
      in response to various inducers. It is accompanied by typical morphological
      changes, in addition to the secretion of bioactive molecules, including
      proinflammatory cytokines and chemokines [known as the senescence-associated
      secretory phenotype (SASP)]. Thus, senescent cells may affect their local
      environment and induce a so-called 'bystander' senescence through the state of
      SASP. The phenotypes of senescent cells are determined by the type of agent
      inducing cellular stress and the cell lineages. To characterise the phenotypes of
      senescent cancer cells, two murine cell lines were employed in the present study:
      TC-1 and B16F10 (B16) cells. Two distinct senescence inductors were used:
      Chemotherapeutic agent docetaxel (DTX) and a combination of immunomodulatory
      cytokines, including interferon gamma (IFNgamma) and tumour necrosis factor alpha
      (TNFalpha). It was demonstrated that DTX induced senescence in TC-1 and B16
      tumour cell lines, which was demonstrated by growth arrest, positive beta
      galactosidase staining, increased p21Waf1 (p21) expression and the typical SASP
      capable of inducing a 'bystander' senescence. By contrast, treatment with a
      combination of T helper cell 1 cytokines, IFNgamma and TNFalpha, induced
      proliferation arrest only in B16 cells. Despite the presence of certain
      characteristic features resembling senescent cells (proliferation arrest,
      morphological changes and increased p21 expression), these cells were able to
      form tumours in vivo and started to proliferate upon cytokine withdrawal. In
      addition, B16 cells were not able to induce a 'bystander' senescence. In summary,
      the present study described cell line- and treatment-associated differences in
      the phenotypes of senescent cells that may be relevant in optimization of cancer
      chemo- and immunotherapy.

PMID- 30226597
TI  - Induction of apoptosis and G1 phase cell cycle arrest by Aster incisus in AGS
      gastric adenocarcinoma cells.
AB  - In recent decades, various bioactive compounds from plants have been investigated
      for their potential use in the treatment of diseases in humans. Aster incisus
      extract (AIE) is the extract of a common plant that is mostly found in Asia. It
      has traditionally been used for medicinal purposes in South Korea. In this study,
      we evaluated the potential anticancer effects of a methanolic extract of Aster
      incisus in a normal human cell line (HaCaT keratinocytes) and in 4 different
      types of human cancer cell lines (A549, lung cancer; Hep3B, liver cancer; MDA-MB
      231, breast cancer; and AGS, gastric cancer). The HaCaT, A549, Hep3B, MDA-MB-231
      and AGS cells were treated with various concentrations of AIE and following
      treatment, cell survival was evaluated. Additional analyses, such as WST-1 assay,
      western blot analysis, DAPI staining, flow cytometry, immunofluorescence staining
      and wound healing assay were performed to elucidate the mechanisms and pathways
      involved in the cell death induced by AIE. Treatment with AIE induced
      morphological changes and considerably reduced the viability of the both normal
      and cancer cell lines. Further analysis of the AGS gastric cancer cells revealed
      that AIE led to the induction of apoptosis and a high accumulation of cells in
      the G1 cell phase following treatment with AIE in a dose-dependent manner. The
      results also revealed that AIE successfully suppressed the migration of the AIE
      treated AGS cells. The results of western blot analysis indicated that AIE
      increased the expression of pro-apoptotic proteins, particularly Bid, Bad, Bak,
      cytochrome c, apoptosis inducing factor (AIF), cleaved caspase-3, -8 and -9 and
      cleaved poly(ADP-ribose) polymerase (PARP). Additionally, AIE decreased the
      expression of the anti-apoptotic proteins, Bcl-2 and Bcl-xL. On the whole, the
      findings of this study demonstrate that AIE induces apoptosis through the
      activation of the caspase-dependent pathway mediated by the mitochondrial pathway
      and by arresting the cell cycle in AGS cells.

PMID- 30226596
TI  - P2Y2R-mediated inflammasome activation is involved in tumor progression in breast
      cancer cells and in radiotherapy-resistant breast cancer.
AB  - In the tumor microenvironment, extracellular nucleotides are released and
      accumulate, and can activate the P2Y2 receptor (P2Y2R), which regulates various
      responses in tumor cells, resulting in tumor progression and metastasis.
      Moreover, the inflammasome has recently been reported to be associated with tumor
      progression. However, the role of P2Y2R in inflammasome activation in breast
      cancer cells is not yet well defined. Therefore, in this study, we investigated
      the role of P2Y2R in inflammasome-mediated tumor progression in breast cancer
      using breast cancer cells and radiotherapy-resistant (RT-R) breast cancer cells.
      We established RT-R-breast cancer cells (RT-R-MDA-MB-231, RT-R-MCF-7, and RT-R
      T47D cells) by repeated irradiation (2 Gy each, 25 times) in a previous study. In
      this study, we found that the RT-R breast cancer cells exhibited an increased
      release of adenosine triphosphate (ATP) and P2Y2R activity. In particular, the RT
      R-MDA-MB-231 cells derived from highly metastatic MDA-MB-231 cells, exhibited a
      markedly increased ATP release, which was potentiated by tumor necrosis factor
      (TNF)-alpha. The MDA-MB-231 cells exhibited inflammasome activation, as measured
      by caspase-1 activity and interleukin (IL)-1beta secretion following treatment
      with TNF-alpha and ATP; these effects were enhanced in the RT-R-MDA-MB-231 cells.
      However, the increased caspase-1 activities and IL-1beta secretion levels induced
      in response to treatment with TNF-alpha or ATP were significantly reduced by
      P2Y2R knockdown or the presence of apyrase in both the MDA-MB-231 and RT-R-MDA-MB
      231 cells, suggesting the involvement of ATP-activated P2Y2R in inflammasome
      activation. In addition, TNF-alpha and ATP increased the invasive and colony
      forming ability of the MDA-MB-231 and RT-R-MDA-MB-231 cells, and these effects
      were caspase-1-dependent. Moreover, matrix metalloproteinase (MMP)-9 activity was
      modulated by caspase-1, in a P2Y2R-dependent manner in the MDA-MB-231 and RT-R
      MDA-MB-231 cells. Finally, nude mice injected with the RT-R-MDA-MB-231-EV cells
      (transfected with the empty vector) exhibited increased tumor growth, and higher
      levels of MMP-9 in their tumors and IL-1beta levels in their serum compared with
      the mice injected with the RT-R-MDA-MB-231-P2Y2R shRNA cells (transfected with
      P2Y2R shRNA). On the whole, the findings of this study suggest that extracellular
      ATP promotes tumor progression in RT-R-breast cancer cells and breast cancer
      cells by modulating invasion and associated molecules through the P2Y2R
      inflammasome activation pathway.

PMID- 30226598
TI  - miR-21-5p targets PDHA1 to regulate glycolysis and cancer progression in gastric
      cancer.
AB  - Pyruvate dehydrogenase A1 (PDHA1) is a component of the pyruvate dehydrogenase
      enzyme complex, which links glycolysis and the tricarboxylic acid cycle, and is
      important for cancer metabolism shift. PDHA1 downregulation has been revealed in
      several types of cancer to enhance glycolysis. However, the role of PDHA1 in
      gastric cancer remains largely unknown. In the present study, we found that PDHA1
      was significantly downregulated in gastric cancer, and associated with poor
      prognosis. PDHA1 downregulation promoted gastric cancer glycolysis and cancer
      progression. miR-21-5p directly targeted PDHA1 to suppress PDHA1 expression, and
      promote glycolysis as well as cell proliferation in gastric cancer. Moreover, miR
      21-5p was significantly upregulated in gastric cancer and negatively associated
      with PDHA1 expression in gastric cancer samples. Our results indicated that miR
      21-5p targeted PDHA1 to regulate a metabolic switch and cancer progression in
      gastric cancer, and reveal the potential role of the miR-21-5p/PDHA1 axis in
      gastric cancer treatment.

PMID- 30226599
TI  - 18F-alfatide positron emission tomography may predict anti-angiogenic responses.
AB  - As the crucial issue in the development of anti-angiogenic drugs is how to
      predict which patients will and will not benefit prior to the initiation of
      therapy, angiogenic 18F-alfatide positron emission computed tomography (PET) was
      assessed in the present study. Lung adenocarcinoma A549 (high angiogenesis) and
      prostate PC-3 (low angiogenesis) cell xenografted tumor-bearing mice underwent
      18F-alfatide PET at baseline and following treatment with either an anti
      angiogenic therapy or vehicle. The evaluation index for the inhibition of tumor
      growth in the individuals in the treated groups was represented by
      treatment/control (T/C) ratio (%). Anti-angiogenic responses were denoted by the
      changes in 18F-alfatide uptake in the same animal. The T/C ratio was lower in
      high-uptake tumors than in low-uptake tumors (P=0.001). A significant difference
      in the tumor volumes between the anti-angiogenic therapy group and the control
      group occurred earlier in the A549 model than in the PC-3 model. 18F-alfatide
      uptake decreased more for A549 tumors than for PC-3 tumors following anti
      angiogenic therapy. In each treatment group, the degree of tumor response to anti
      angiogenic therapy was associated well with the tumor uptake prior to treatment
      (P<0.05). These results indicated that 18F-alfatide PET may be a useful molecular
      imaging tool for individual selection prior to anti-angiogenic drug therapy.

PMID- 30226600
TI  - Rotundic acid enhances the impact of radiological toxicity on MCF-7 cells through
      the ATM/p53 pathway.
AB  - Although radiation therapy is a powerful anticancer modality, radiation- induced
      stress response and gene expression with adaptive resistance may severely
      compromise the effectiveness of radiation. The function of rotundic acid (RA) on
      inducing apoptosis in the human breast cancer cell line MCF-7 has been
      investigated in a previous study. In the present study, the combined effect of
      chemotherapy and radiotherapy on reducing side effects was examined. The results
      of an MTT assay revealed that radiation (0.5, 2 and 10 Gy) effectively inhibit
      MCF-7 cell viability in a dose-dependent manner, consistent with the effects of
      RA (2, 5 and 12.5 uM). Interestingly, a lower dose of radiation (1 Gy) combined
      with RA (5 uM) exhibited a greater inhibition efficiency compared with a high
      dose of radiation alone. Flow cytometry revealed that radiation combined with RA
      induced the apoptosis of MCF-7 cells. Using western blotting, it was demonstrated
      that radiation induced the expression of ataxia-telangiectasia mutated (ATM) and
      p53 protein, and that RA enhanced this effect. On examining the potential
      underlying mechanism, it was revealed that radiation and RA combined induce Bcl-2
      associated X protein expression and cell apoptosis in MCF-7 cells. An ATM
      inhibitor was able to restore the effect of radiation and RA on inducing MCF-7
      cell apoptosis. These results suggest that the ATM/p53 pathway directly
      participates in radiation and RA-induced apoptosis in MCF-7 cells. RA has the
      potential for development as a novel drug for the treatment of human breast
      cancer combined with radiation therapy, given that the combined side effects are
      reduced.

PMID- 30226601
TI  - The interaction between miR-148a and DNMT1 suppresses cell migration and invasion
      by reactivating tumor suppressor genes in pancreatic cancer.
AB  - DNA methylation is an epigenetic mechanism that cells use to control gene
      expression, which serves an important role in tumorigenesis. DNA
      methyltransferase 1 (DNMT1) is responsible for the maintenance of the pattern of
      DNA methylation. Overexpression of DNMT1 is observed in numerous malignant
      tumors, including pancreatic cancer, and results in silencing of several key
      tumor suppressor genes (TSGs). Recent studies have suggested that microRNAs
      (miRNAs/miRs) contribute to the regulation of DNMT1 expression, and promoter
      hypermethylation caused by DNMT1 overexpression is associated with the
      dysfunction of some miRNAs. The present study aimed to reveal the interaction
      between miR-148a and DNMT1, and its effects on cell proliferation, migration and
      invasion of pancreatic cancer cells. Initially, the expression levels of DNMT1
      and miR-148a were detected in pancreatic cancer tissues and AsPC-1 cells by
      reverse transcription-quantitative polymerase chain reaction (PCR). Secondly, the
      regulatory effects of DNMT1 on miR-148a were evaluated using methylation-specific
      PCR. Furthermore, bioinformatics analysis and dual luciferase reporter assay were
      used to verify the target relationship between miR-148a and DNMT1. Finally, in
      vitro rescue experiments were conducted to evaluate the effects of miR-148a on
      the expression of TSGs and the malignant phenotype in AsPC-1 cells. The results
      demonstrated that DNMT1 was aberrantly upregulated in pancreatic cancer, and was
      responsible for hypermethylation of the miR-148a promoter. Furthermore, DNMT1 was
      revealed as a direct target of miR-148a by dual luciferase reporter assay, and
      restoration of miR-148a could reactivate TSGs, such as p16, preproenkephalin and
      Ras association domain family member 1 by targeting DNMT1 in the AsPC-1
      pancreatic cancer cell line. These results indicated that an interaction exists
      between miR-148a and DNMT1 in pancreatic cancer. Notably, miR-148a overexpression
      significantly inhibited cell proliferation, migration and invasion in AsPC-1
      cells. Therefore, miR-148a may serve as a novel therapeutic target for the
      treatment of pancreatic cancer.

PMID- 30226602
TI  - Identification of MMP9 as a novel key gene in mantle cell lymphoma based on
      bioinformatic analysis and design of cyclic peptides as MMP9 inhibitors based on
      molecular docking.
AB  - Mantle cell lymphoma (MCL) is an aggressive disease. MCL is associated with poor
      patient prognosis and limited survival. To identify key genes and explore
      targeting cyclic peptide inhibitors for the treatment of MCL, we downloaded two
      gene expression profiles (GSE32018 and GSE9327) from the Gene Expression Omnibus
      (GEO) database. We screened 84 differentially expressed genes (DEGs). Pathway
      analysis showed that DEMs were mainly enriched in the 'Pathway in cancer', 'PI3K
      Akt signaling pathway', 'Cytokine-cytokine receptor interaction', 'Rap1 signaling
      pathway', 'NF-kappaB signaling pathway' and 'Leukocyte trans-endothelial
      migration'. We subsequently constructed a protein-protein interaction (PPI)
      network of DEGs. In addition, matrix metalloproteinase 9 (MMP9) with a high
      degree in the PPI network was identified as a hub gene in MCL. Meanwhile in the
      Molecular Complex Detection (MCODE) analysis, MMP9 was located in the important
      cluster. Thus, MMP9 can be used as a therapeutic target for MCL and we designed
      cyclic peptides as MMP9 inhibitors. MMP9 protein structure was gathered from the
      Protein Data Bank (PDB), with a PDB ID: 1L6J. MMP9 and cyclic peptides were
      docked using Molecular Operating Environment (MOE) software after structural
      optimization. It was revealed that cyclic peptide 2 bound deeply in the binding
      pocket of MMP9 and had interaction with the active-site Zn2+ ion in the catalytic
      domain. Cyclic peptides 1, 2, 4-6 also displayed potential interaction with
      active residues of MMP9; thus, these cyclic peptides can serve as potential drug
      candidates to block MMP9 activity and future studies are warranted to confirm
      their efficacy.

PMID- 30226603
TI  - Overexpression of Epsin 3 enhances migration and invasion of glioma cells by
      inducing epithelial-mesenchymal transition.
AB  - Epsin 3 (EPN3) expression is limited to gastric parietal cells and wounded or
      pathological tissue rather than normal brain tissue, and although it has been
      identified as an oncogene in estrogen receptor-positive breast cancer and non
      small cell lung cancer, its function in cancer is poorly understood. The present
      study aimed to investigate the association of EPN3 expression with the
      clinicopathological features of patients with glioma, as well as the effects of
      EPN3 on glioblastoma cells and the potential molecular mechanisms for its effects
      on glioblastoma cell behavior. EPN3 expression was assessed by
      immunohistochemistry in tissue samples from 167 patients with glioma, as well as
      by western blotting in 5 glioblastoma cell lines. The U87 and U251 glioblastoma
      cell lines were used to investigate the effects of EPN3 on glioblastoma cell
      invasion and migration through gain and loss of EPN3 expression experiments;
      expression levels were further investigated by reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) and western blot analyses. The results
      demonstrated that EPN3 expression levels were upregulated in high-grade glioma
      tissues compared with low-grade tissues, and there were varying expression levels
      of EPN3 in the five glioblastoma cell lines. No significant differences were
      observed in EPN3 expression in relation to patient age, sex or tumor size.
      Overexpression of EPN3 promoted glioblastoma cell migration and invasion, which
      we hypothesized was through affecting epithelial-mesenchymal transition (EMT). RT
      qPCR and western blotting revealed that EPN3 upregulation increased the
      expression of Notch1 intracellular domain, beta-catenin, Slug, Twist and zinc
      finger E-box-binding homeobox (ZEB)-1. These results suggested that EPN3 enhances
      the migration and invasion of glioblastoma cells by activating the transcription
      factors Slug, Twist and ZEB1, but not Snail 1 or ZEB2, to induce EMT in glioma
      cells; EPN3 involvement in the Notch and WNT/beta-catenin signaling pathways may
      contribute to this process.

PMID- 30226604
TI  - Epigenetic roles of PIWI-interacting RNAs (piRNAs) in cancer metastasis (Review).
AB  - P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are epigenetic
      related short ncRNAs that participate in chromatin regulation, transposon
      silencing, and modification of specific gene sites. These epigenetic factors or
      alterations are also involved in the growth of a variety of human cancers,
      including lung, breast, and colon cancer. Accumulating evidence has revealed that
      tumor metastasis and invasion involve genetic and epigenetic factors. Cancer
      metastasis is characterized by epigenetic alterations including DNA methylation
      and histone modification. Changes in DNA methylation, H3K9me3 heterochromatin and
      transposable elements have been detected in several cancers. piRNAs may function
      in gene silencing and gene modification upstream or downstream of oncogenes in
      cancer cell lines or cancer tissues. In addition to piRNAs, PIWI proteins can be
      used as biomarkers for prognosis, diagnosis and clinical evaluation and may be
      factors in cancer metastasis. Here, we elucidated the possible mechanisms by
      which piRNAs regulate cancer metastasis, including but not restricted to
      influencing DNA and histone methylation and transposable elements.

PMID- 30226605
TI  - STAT1-HDAC4 signaling induces epithelial-mesenchymal transition and sphere
      formation of cancer cells overexpressing the oncogene, CUG2.
AB  - Our previous studies have shown that the novel oncogene, cancer upregulated gene
      2 (CUG2), activates STAT1, which is linked to anticancer drug resistance, induces
      epithelial-mesenchymal transition (EMT) and cancer stem cell-like phenotypes as
      determined by MTT, migration and sphere formation assays. We thus aimed to
      ascertain whether the activation of STAT1 by CUG2 is involved in these malignant
      phenotypes besides drug resistance. Here, we showed that STAT1 suppression
      decreased the expression of N-cadherin and vimentin, biomarkers of EMT, which led
      to inhibition of the migration and invasion of human lung A549 cancer cells
      stably expressing CUG2, but did not recover E-cadherin expression. STAT1 siRNA
      also diminished CUG2-induced TGF-beta signaling, which is critical in EMT, and
      TGF-beta transcriptional activity. Conversely, inhibition of TGF-beta signaling
      reduced phosphorylation of STAT1, indicating a crosstalk between STAT1 and TGF
      beta signaling. Furthermore, STAT1 silencing diminished sphere formation, which
      was supported by downregulation of stemness-related factors such as Sox2, Oct4,
      and Nanog. Constitutive suppression of STAT1 also inhibited cell migration,
      invasion and sphere formation. As STAT1 acetylation counteracts STAT1
      phosphorylation, acetylation of STAT1 by treatment with trichostatin A, an
      inhibitor of histone deacetylases (HDACs), reduced cell migration, invasion, and
      sphere formation. As HDAC4 is known to target STAT1, its role was investigated
      under CUG2 overexpression. HDAC4 suppression resulted in inhibition of cell
      migration, invasion, and sphere formation as HDAC4 silencing hindered TGF-beta
      signaling and decreased expression of Sox2 and Nanog. Taken together, we suggest
      that STAT1-HDAC4 signaling induces malignant tumor features such as EMT and
      sphere formation in CUG2-overexpressing cancer cells.

PMID- 30226606
TI  - Increasing HER2 alpha2,6 sialylation facilitates gastric cancer progression and
      resistance via the Akt and ERK pathways.
AB  - Upregulated beta-galactoside alpha2,6-sialyltransferase I (ST6Gal-I) expression
      reportedly occurs in many cancers and is correlated with metastasis and poor
      prognosis. However, the mechanisms by which ST6Gal-I facilitates gastric cancer
      progression remain poorly understood. Trastuzumab is exclusively used in human
      epidermal growth factor receptor 2 (HER2)+ gastric cancers; however, most
      advanced HER2+ gastric cancers develop trastuzumab resistance. Herein, we
      identified HER2 as an ST6Gal-I substrate and showed that HER2 alpha2,6
      sialylation confers protection against trastuzumab-mediated apoptosis. SGC7901
      cancer cell models in which ST6Gal-I was overexpressed or knocked down were
      constructed, revealing that ST6Gal-I overexpression induced high HER2 sialylation
      levels and increased cell viability and invasion compared to those in the vector
      cell line under serum starvation; ST6Gal-I knockdown had the opposite effects.
      ST6Gal-I overexpression also potentiated cell cycle arrest in the G2/S phase to
      reduce drug sensitivity. In addition, FACS analysis revealed that high ST6Gal-I
      levels increased resistance to trastuzumab-induced apoptosis, accompanied by
      decreased caspase-3 levels. However, the ST6Gal-I knockdown cell line revealed
      increased caspase-3 levels and evident apoptosis compared with those in the
      vector cell line. Although ST6Gal-I overexpression increased HER2 sialylation,
      corresponding to decreased HER2 phosphorylation, high alpha2,6-sialylation
      enhanced Akt and ERK phosphorylation levels compared to those in the vector cell
      line; ST6Gal-I knockdown had the opposite effects. Collectively, these results
      implicated a functional role of ST6Gal-I in promoting tumor cell progression and
      trastuzumab resistance.

PMID- 30226607
TI  - 2'-Hydroxyflavanone inhibits epithelial-mesenchymal transition, and cell
      migration and invasion via suppression of the Wnt/beta-catenin signaling pathway
      in prostate cancer.
AB  - Despite the availability of a number of treatment options, certain cases of
      primary prostate cancer (PCa) will develop into metastatic PCa, in which
      epithelial-mesenchymal transition (EMT) serves an important role. Recently, a
      natural flavonoid known as 2'-hydroxyflavanone (2HF) exerts remarkable anticancer
      activity on various types of cancer. Our previous study demonstrated that 2HF
      could promote apoptosis and inhibit the proliferation of PCa cells, but whether
      2HF is involved in the regulation of EMT, and cell migration and invasion in
      metastatic PCa remains unknown. The present study used two different metastatic
      PCa cell lines (PC-3 and DU145) to investigate the effects of 2HF on EMT, and
      cell migration and invasion. The results demonstrated that 2HF could inhibit EMT,
      and cell migration and invasion through the Wnt/beta-catenin signaling pathway by
      suppressing GSK-3beta phosphorylation, beta-catenin expression and
      transactivation. In conclusion, the present study revealed a novel function of
      2HF, which may be used to prevent or treat PCa metastasis.

PMID- 30226608
TI  - Generation of PTEN-knockout (-/-) murine prostate cancer cells using the
      CRISPR/Cas9 system and comprehensive gene expression profiling.
AB  - Phosphatase and tensin homolog (PTEN) deficiency is associated with development,
      progression, and metastasis of various cancers. However, changes in gene
      expression associated with PTEN deficiency have not been fully characterized. To
      explore genes with altered expression in PTEN-deficient cells, the present study
      generated a PTEN-knockout cell line (DeltaPTEN) from a mouse prostate cancer
      derived cell line using the clustered regularly interspaced short palindromic
      repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) gene editing system.
      Following transfection of the CRISPR/Cas9 construct, DNA sequencing was performed
      to identify deletion of the Pten locus and PTEN inactivation was verified by
      western blotting. The DeltaPTEN cell line exhibited enhanced RAC-alpha
      serine/threonine-protein kinase phosphorylation and cyclin D1 expression. In
      addition, an increase in cell proliferation and colony formation was observed in
      the DeltaPTEN cell line. Gene expression profiling experiments were analyzed with
      microarray and microRNA (miRNA) arrays. In the microarray analysis, 111 genes
      exhibited >=10-fold increased expression compared with the parent strain and mock
      cell line and 23 genes were downregulated. The only miRNA with increased
      expression of 10-fold or more was mmu-miR-210-3p. Genes with enhanced expression
      included genes involved in the development, progression, and metastasis of cancer
      such as Tet methylcytosine dioxygenase 1, twist family BHLH transcription factor
      2, C-fos-induced growth factor and Wingless-Type MMTV Integration Site Family,
      Member 3, and genes involved in immunosuppression such as Arginase 1. The results
      of the present study suggest that PTEN deficiency mobilizes a variety of genes
      critical for cancer cell survival and host immune evasion.

PMID- 30226610
TI  - APOBEC3B is expressed in human glioma, and influences cell proliferation and
      temozolomide resistance.
AB  - Highly malignant gliomas are characterized by pronounced intra- and intertumoral
      heterogeneity. On the genetic level, this heterogeneity may be caused by
      spontaneous mutation events, but recent studies have reported distinct mutational
      signatures that may be caused by an enzyme family with cytidine desaminase
      activity, the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like
      (APOBEC) proteins. Among these, APOBEC3B contributes to tumor progression in a
      variety of types of tumor, including breast cancer. In the present study, the
      expression of APOBEC3B was detected at the mRNA and protein levels in solid human
      glioma tissue and human glioma cell lines. In vitro, treatment with temozolomide,
      the most commonly used chemotherapeutic in glioma therapy, induced APOBEC3B
      expression. Furthermore, the knockdown of APOBEC3B by clustered regularly
      interspaced short palindromic repeats/CRISPR associated protein 9 resulted in
      reduced proliferation and enhanced chemosensitivity of glioma cells. Thus,
      APOBEC3B contributes to glioma progression and may be a future target for
      therapeutic intervention.

PMID- 30226609
TI  - hsa-miR-24 suppresses metastasis in nasopharyngeal carcinoma by regulating the c
      Myc/epithelial-mesenchymal transition axis.
AB  - Distant metastasis is the major contributor to treatment failure and mortality in
      patients with nasopharyngeal carcinoma (NPC). The lack of effective treatment
      strategies for metastatic NPC is the major cause for the low survival rate.
      Therefore, it is crucial to understand the molecular mechanisms underlying NPC
      metastasis and to identify potential biomarkers for targeted therapy. MicroRNA
      (miRNAs or miRs) have been shown to play an important role in tumorigenesis and
      metastasis. In the present study, we aimed to evaluate the significance of hsa
      miR-24 in NPC metastasis. Significantly lower hsa-miR-24 levels were observed in
      NPC metastatic tumors and higher hsa-miR-24 levels were associated with longer
      progression-free and metastasis-free survival durations. hsa-miR-24
      overexpression inhibited cell proliferation, invasion and migration. Using
      bioinformatics approaches together with functional luciferase reporter assays, we
      demonstrated that the c-Myc 3'-UTR was a direct target of hsa-miR-24 in
      regulating NPC metastasis. Protein profiling analysis revealed that a high c-Myc
      expression was inversely associated with metastasis-free overall survival and
      with epithelial-mesenchymal transition (EMT). Furthermore, the overexpression of
      hsa-miR-24 decreased NPC cell invasive ability induced by the overexpression of c
      Myc, associated with EMT epithelial marker (E-cadherin) restoration. Thus, on the
      whole, the findings of this study demonstrate that hsa-miR-24 suppresses
      metastasis in NPC by regulating the c-Myc/EMT axis, suggesting that hsa-miR-24
      may be used as a prognostic factor and as a novel target for the prevention of
      NPC metastasis.

PMID- 30226611
TI  - Allergen-removed Rhus verniciflua Stokes suppresses invasion and migration of
      pancreatic cancer cells through downregulation of the JAK/STAT and Src/FAK
      signaling pathways.
AB  - Pancreatic cancer is a leading cause of mortality and morbidity worldwide. Due to
      drug resistance, and the high toxicity and adverse side effects of existing
      chemotherapeutic drugs, the current treatment of highly aggressive pancreatic
      cancer is considered inadequate. Allergen-removed Rhus verniciflua Stokes (aRVS)
      has a strong antiproliferative effect in various cancer cells, and due to its low
      toxicity, it has emerged as an attractive candidate for cancer treatment.
      However, the potential use of aRVS as a treatment for pancreatic cancer is
      relatively unexplored. The present study examined the effects of aRVS on the
      invasion and migration of pancreatic cancer cells, and identified the molecular
      mechanisms underlying its anticancer effects. aRVS inhibited the Janus
      kinase/signal transducer and activator of transcription pathway in pancreatic
      cancer cells, and decreased the protein expression of mucin 4. In addition, it
      inhibited the activation of focal adhesion kinase and Src signaling, and
      decreased the expression of matrix metalloproteinase 9, which may reduce the
      migration and invasion of pancreatic cancer cells. In conclusion, the present
      study suggested that aRVS may be a potential treatment for aggressive pancreatic
      cancer.

PMID- 30226612
TI  - Norepinephrine enhances cell viability and invasion, and inhibits apoptosis of
      pancreatic cancer cells in a Notch-1-dependent manner.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of
      cancer, which is associated with a poor prognosis due to complexities in
      prevention, early diagnosis and effective treatment. The lack of understanding
      regarding its induction and specific pro-cancer mechanisms may contribute to its
      poor prognosis. The Notch-1 pathway is widely considered to be a critical tumor
      promoting factor in PDAC. Previous studies have indicated that chronic
      psychological stress may promote the development of PDAC partially via the main
      downstream stress hormone, norepinephrine (NE); however, to the best of our
      knowledge, the role of the Notch-1 pathway in this process has not been studied.
      Therefore, the present study aimed to explore this process. The expression levels
      of Notch-1 pathway-associated molecules were measured in response to NE using
      reverse transcription-quantitative polymerase chain reaction and western
      blotting. Alongside NE treatment, two Notch-1 pathway blockers, Notch-1-specific
      small interfering (si)RNA and DAPT (an inhibitor of the Notch-1 pathway), were
      used to explore the relationship between NE and the Notch-1 pathway in the
      development of pancreatic cell malignant biological behaviors, including cell
      viability, apoptosis and cell invasion. The results demonstrated that treatment
      with NE enhanced cell viability and invasion, and inhibited apoptosis of PDAC
      cells; however, these effects were suppressed following treatment with Notch-1
      specific siRNA and DAPT. In conclusion, NE may enhance the malignant biological
      behaviors of PDAC via activating the Notch-1 pathway.

PMID- 30226613
TI  - UCA1 overexpression is associated with less aggressive subtypes of bladder
      cancer.
AB  - Non-coding RNAs (ncRNAs) have been shown to serve important roles in
      carcinogenesis via complex mechanisms, including transcriptional and post
      transcriptional regulation, and chromatin interactions. Urothelial carcinoma
      associated 1 (UCA1), a long ncRNA, was recently shown to have tumorigenic
      properties in urothelial bladder cancer (UBC), as demonstrated by enhanced
      proliferation, migration, invasion and therapy resistance of UBC cell lines in
      vitro. These in vitro findings suggested that UCA1 is associated with aggressive
      tumor behavior and could have prognostic implications in UBC. The aims of the
      present study were to therefore to investigate the statistical associations
      between UCA1 RNA expression and UBC pathological features, patient prognosis and
      p53 and Ki-67 expression. Chromogenic in situ hybridization and
      immunohistochemistry were performed on UBC tissue microarrays to characterize
      UCA1 RNA, and p53 and Ki-67 expression in 208 UBC cases, including 145 non-muscle
      invasive and 63 muscle-invasive cases. UCA1 was observed in the tumor cells of
      166/208 (80%) UBC cases tested. No expression was noted in normal stromal and
      endothelium cells. Patients with UBC that overexpressed UCA1 (35%) had a
      significantly higher survival rate (P=0.006) compared with that in patients with
      UBC that did not overexpress UCA1. This prognostic factor was independent of
      tumor morphology, concomitant carcinoma in situ, tumor grade and tumor stage. In
      addition, the absence of UCA1 overexpression was significantly associated with a
      high Ki-67 proliferative index (P=0.008) and a p53 'mutated' immunoprofile
      (strong nuclear expression or complete absence of staining; P=0.003). In
      conclusion, the present results identified UCA1 as potentially being a novel
      independent prognostic marker in UBC that was associated with a better patient
      prognosis and that could serve a pivotal role in bladder cancer carcinogenesis.

PMID- 30226614
TI  - KLF5 promotes the tumorigenesis and metastatic potential of thyroid cancer cells
      through the NF-kappaB signaling pathway.
AB  - The purpose of the present study was to identify the potential function of
      Kruppel-like factor 5 (KLF5) in thyroid cancer and investigate the underlying
      mechanisms. The protein levels of KLF5 in 98 thyroid cancer tissues were analyzed
      using an immunohistochemistry assay. SW579 cells transfected with small
      interfering RNA against KLF5 and B-CPAP cells transfected with KLF5 expressing
      vectors were used for functional studies. Western blot analysis,
      immunofluorescence and co-immunoprecipitation assays were used to investigate the
      mechanisms of KLF5. In vivo tumorigenicity was assessed using a subcutaneous
      xenograft experiment. The results revealed that KLF5 was highly expressed in
      thyroid cancer tissues and associated with lymph node metastasis. Knockdown of
      KLF5 in SW579 cells suppressed proliferation, anchorage-independent growth,
      migration and invasion in vitro, while the overexpression of KLF5 resulted in
      opposite effects in B-CPAP cells. Mechanistically, it was demonstrated that KLF5
      promoted the cytoplasm-nuclear translocation of nuclear factor-kappaB.
      Additionally, it was revealed that insufficient F-box/WD repeat-containing
      protein 7 expression may be responsible for the dysfunction of KLF5 in thyroid
      cancer. These results revealed that KLF5 promotes the tumorigenesis and
      metastasis of thyroid cancer cells and may be a potential therapeutic target in
      patients with thyroid cancer.

PMID- 30226615
TI  - Downregulation of DLL4 predicts poor survival in non-small cell lung cancer
      patients due to promotion of lymph node metastasis.
AB  - Delta-like 4 (DLL4) is a membrane-bound ligand, which belongs to the Notch
      signaling pathway and plays important roles in angiogenesis and vascular
      development. The expression of DLL4 in non-small cell lung cancer (NSCLC) remains
      unclear. Therefore, DLL4 expression was detected in clinical specimens using
      quantum dots (QDs)-immunohistochemistry (IHC) and lung cancer cell lines by
      quantitative real-time polymerase chain reaction. The protein levels of DLL4 were
      decreased in the tumor tissues of NSCLC patients and lung cancer cell lines.
      Kaplan-Meier analysis indicated that low expression of DLL4 predicted poor
      survival rate of NSCLC patients. A549 and A427 cells transfected with pCMV-DLL4
      exhibited reduced cell proliferation, migration and invasion using MTT assay,
      wound healing assay and Transwell assay. These data indicate that DLL4 represents
      a new prognostic biomarker for NSCLC, and DLL4 overexpression inhibits cell
      proliferation and metastasis in vitro.

PMID- 30226616
TI  - C16-ceramide and sphingosine 1-phosphate/S1PR2 have opposite effects on cell
      growth through mTOR signaling pathway regulation.
AB  - Recently, sphingolipid derivatives, such as ceramide and sphingosine-1-phosphate
      (S1P), have emerged as key modulators in apoptotic cell death and cell
      proliferation. This study aimed to clarify the underlying signaling pathways of
      ceramide and S1P involved in breast cancer cell proliferation. Ceramide acyl
      chain length is determined by six mammalian ceramide synthases (CerS). We
      overexpressed CerS1 to 6 in MCF-7 cells to examine whether ceramide signaling
      propagation varies as a function of acyl chain length. Among the six CerS, only
      CerS6 overexpression reduced phosphorylation of Akt, S6 kinase (S6K), and
      extracellular signal-regulated kinases (ERK) as shown by western blotting. In
      addition, CerS6 overexpression reduced MCF-7 cell proliferation. This effect was
      partially reversed by co-treatment with MHY1485, an activator of mammalian target
      of rapamycin (mTOR), demonstrating an important role for the mTOR pathway in the
      CerS6-mediated decrease in MCF-7 cell proliferation. ERK inhibition, but not Akt
      inhibition, along with mTOR inhibition synergistically reduced MCF-7 cell
      proliferation as measured by MTT assay. Notably, the expression of CerS6 and S1P
      receptor 2 (S1PR2), or CerS6 and sphingosine kinase 1 (SphK1), were negatively
      correlated according to the invasive breast carcinoma patient cohort in The
      Cancer Genome Atlas database. In addition, both SphK1 overexpression and S1P
      addition increased mTOR phosphorylation as shown by ELISA, while S1PR2 inhibition
      had the inverse effect. These data suggest that CerS6 and SphK1 regulate mTOR
      signaling in breast cancer cell proliferation. Moreover, mTOR activity can be
      regulated by the balance between S1P and C16-ceramide, which is generated by
      CerS6.

PMID- 30226617
TI  - TAB3 promotes human esophageal squamous cell carcinoma proliferation and invasion
      via the NF-kappaB pathway.
AB  - Esophageal squamous cell carcinoma (ESCC) has become one of the most common
      causes of cancer-associated mortality worldwide. Transforming growth factor
      activated kinase (TAK1)-binding protein 3 (TAB3) is essential for activation of
      the NF (NF)-kappaB pathway in response to TAK1 activation. The NF-kappaB pathway
      serves important roles in tumor cell proliferation and migration; however, the
      clinical relevance of TAB3 and its biological function in ESCC progression remain
      elusive. The present study investigated the expression and function of TAB3 in
      ESCC tissues, and its association with the clinical prognosis of patients. The
      results demonstrated that TAB3 expression was significantly increased in human
      ESCC cell lines and tissue samples, and the expression of TAB3 was associated
      with ESCC lymph node metastasis, T stage, pathological grade and Ki-67 expression
      in 80 ESCC samples, as determined by immunohistochemistry. Patients with ESCC and
      high TAB3 expression exhibited worse overall survival. Furthermore, knockdown of
      TAB3 by small interfering RNA inhibited the proliferation of ESCC cells, and
      reduced the migration and invasion of ESCC cells. In addition, knockdown of TAB3
      decreased the expression of the NF-kappaB pathway in TE-1 cells. Taken together,
      these results demonstrated that TAB3 may be a promising therapeutic target for
      the treatment of ESCC.

PMID- 30226618
TI  - Sinomenine hydrochloride sensitizes cervical cancer cells to ionizing radiation
      by impairing DNA damage response.
AB  - The use of plant-based compounds derived from traditional medicine to improve
      human diseases has been gaining momentum, due to their high bioavailability and
      moderate adverse effects. Sinomenine is one such biomonomer alkali compound
      derived from Sinomenium acutum and is known for its anti-inflammatory and
      antitumor effects. However, the molecular mechanism(s) of its antitumor
      properties are not fully characterized. In the present study, we evaluated the
      radiosensitizing effects of the water-soluble sinomenine, sinomenine
      hydrochloride (SH) in human cervical cancer cell line (HeLa). SH sensitized HeLa
      cells to ionizing radiation (IR) by promoting accumulation of IR-induced DNA
      double-strand breaks (DSBs) and also by interfering with DNA damage checkpoint
      activation. We then investigated the molecular mechanisms underlying the SH
      mediated cellular sensitization to IR and found that SH inhibited the expression
      of DNA damage response (DDR) factors Ku80 and Rad51 at the transcription level.
      Finally, the radiosensitizing activity of SH was confirmed in a cervical cancer
      mouse xenograft model. The combinatorial treatment of SH and IR significantly
      slowed the tumor growth rate compared with IR alone. Collectively, our study not
      only provides molecular insights into the novel role of SH in cellular response
      to IR, but also suggests a therapeutic potential of SH as a radiosensitizer in
      cervical cancer therapy.

PMID- 30226619
TI  - Biological functions and clinical significance of the newly identified long non
      coding RNA RP1-85F18.6 in colorectal cancer.
AB  - The biological functions of long non-coding RNAs (lncRNAs) in cancer have not
      been fully elucidated. The present study demonstrated that the expression of a
      newly identified lncRNA, RP1-85F18.6, was upregulated in colorectal cancer (CRC)
      tissues and cell lines. Knockdown of lncRNA RP1-85F18.6 served a key role in
      tumor inhibition, reduced cell proliferation and invasion, disrupted the cell
      cycle, and increased apoptosis and pyroptosis of CRC cells. Conversely,
      overexpression of lncRNA RP1-85F18.6 exerted the opposite effects. Furthermore,
      silencing lncRNA RP1-85F18.6 decreased DeltaNp63 expression at both the mRNA and
      protein levels. Furthermore, co-transfection with DeltaNp63 siRNA and lncRNA RP1
      85F18.6-expressing vector attenuated the tumor-promoting effects of lncRNA RP1
      85F18.6 overexpression. The expression levels of lncRNA RP1-85F18.6, DeltaNp63
      and gasdermin D (GSDMD) were revealed to be associated with lymph node and
      distant metastases in patients with CRC, and therefore may serve as predictors in
      CRC. The findings of the present study suggested that lncRNA RP1-85F18.6 may
      trigger CRC cell proliferation, invasion and cell cycle disruption, and suppress
      apoptosis and pyroptosis of CRC cells through regulating DeltaNp63 expression.
      Therefore, lncRNA RP1-85F18.6 and DeltaNp63 may be considered unfavorable
      biomarkers, whereas GSDMD may be a favorable biomarker in CRC; these markers may
      prove valuable in the future diagnosis and prognosis of CRC.

PMID- 30226620
TI  - Inhibition of epithelial-mesenchymal transition in gastric cancer cells by miR
      711-mediated downregulation of CD44 expression.
AB  - Gastric cancer is a common malignancy worldwide. The prognosis of early stage
      gastric cancer patients has significantly improved in recent years. However, in
      progressive stage gastric cancer patients, the prognosis remains relatively poor
      due to tumor metastases. In our previous study, we showed that the expression of
      miR-711 in gastric cancer tissues is low, and restoration of miR-711 inhibited
      the invasion and migration and the occurrence of epithelial-mesenchymal
      transition (EMT) in gastric cancer cells. Yet, the mechanisms involved in these
      processes remain unknown. In the present study, we demonstrated that miR-711
      mediated downregulation of CD44 expression inhibited EMT of gastric cancer cells
      in vitro and in vivo by downregulating vimentin protein expression and
      upregulating E-cadherin protein expression through transfection, qRT-PCR and
      western blotting. Therefore, miR-711 may provide a promising target for EMT
      related therapy for gastric cancer.

PMID- 30226621
TI  - [Retracted] Long non-coding RNA MALAT1 interacts with miR-124 and modulates
      tongue cancer growth by targeting JAG1.
AB  - We wish to retract our research article entitled "Long non-coding RNA MALAT1
      interacts with miR-124 and modulates tongue cancer growth by targeting JAG1"
      published in Oncology Reports 37 2087-2094, 2017. Following the publication of
      this article, it was drawn to our attention that this paper bore numerous
      similarites with an article published previously in the journal OncoTargets and
      Therapy. Although all the data reported in our study were original, we recognize
      that it was not appropriate that we should have modelled our paper on previously
      published articles as a template on which to base the writing of our paper.
      Therefore, we have agreed to follow the Editor's recommendation that this paper
      be retracted from the publication. All the named authors agree to this
      retraction. We sincerely apologize to the Editor and the readership of the
      Journal for our action, and regret any inconvenience this has caused. [the
      original article was published in the Oncology Reports 37: 2087-2094, 2017; DOI:
      10.3892/or.2017.5445].

PMID- 30226622
TI  - EGF ligand fused to truncated Pseudomonas aeruginosa exotoxin A specifically
      targets and inhibits EGFR-positive cancer cells.
AB  - Cancer cells have been known to overexpress the epidermal growth factor receptor
      (EGFR) and hence relevant multiple-targeted therapies have been developed, with a
      recent clinical application of the antibody-mediated inhibition of the EGFR.
      However, this strategy is not useful in cancer cells with mutations in KRAS; a
      GTPase downstream of EGFR which constitutively activates the pathway without EGF
      stimulation. Furthermore, mutations in EGFR also reduce the binding of monoclonal
      antibodies and thereby render them ineffective. In the present study, we designed
      a chimeric EGF protein fused to the truncated N-terminal domain fragment of
      Pseudomonas aeruginosa exotoxin A (EGF-ETA), which has ADP-ribosylation activity
      and induces apoptosis. The EGF-ETA protein was expressed in E. coli as a His
      tagged fusion. Our results showed that EGF-ETA significantly inhibited the
      proliferation of EGFR-positive A431 epidermoid carcinoma (IC50 27 ng/ml) and HN5
      head and neck squamous cell carcinoma (IC50 36 ng/ml) cells. However, its effect
      on cancer cells with little or no EGFR expression was limited (A549-IC50 1,000
      ng/ml; MCF-7-IC50 >10,000 ng/ml). Compared to cetuximab, EGF-ETA was highly
      potent in its killing capacity of HN5 cancer cells at 1,000 ng/ml, while
      cetuximab had little effect at 1,000 ng/ml. Furthermore, EGF-ETA was just as
      potent in HCT116 (KRAS G13D) and SW480 (KRAS G12V) colon cancer cell lines
      harbouring KRAS hyperactivating mutations when compared to KRAS wild-type HT29
      colon cancer cells. Finally, co-incubation of EGF-ETA with an anti-EGF antibody
      abrogated its effect on the EGFR-positive A431 cells. Our results show that the
      chimeric EGF-ETA toxin is extremely effective against EGFR-positive cancers and
      raises the potential to further develop this chimera for use in targeting EGFR
      positive tumours resistant to monoclonal antibodies.

PMID- 30226623
TI  - Thymosin beta4 is associated with bone sialoprotein expression via ERK and Smad3
      signaling pathways in MDPC-23 odontoblastic cells.
AB  - Thymosin beta4 (Tbeta4) regulates the expression of molecules associated with
      dentinogenesis, including bone sialoprotein (BSP). BSP regulates the initiation
      of mineralization and the direction of dentin growth. However, the association
      between Tbeta4 signaling and BSP expression in odontoblasts remains unclear.
      Therefore, the aim of the present study was to investigate Tbeta4 mRNA expression
      in odontoblasts during dentinogenesis and the association between the Tbeta4
      signaling pathway and BSP expression in MDPC-23 odontoblastic cells. Expression
      and localization of Tbeta4 mRNA was determined by in situ hybridization during
      mouse tooth development. The effect of Tbeta4 signaling on BSP expression was
      investigated by reverse transcription polymerase chain reaction, western blot
      analysis, immunofluorescence and a luciferase reporter assay in the presence or
      absence of specific inhibitors of mitogen activated protein kinase kinase
      (PD98059) and mothers against decapentaplegic homolog 3 (Smad3; SIS3) in MDPC-23
      cells. The expression of Tbeta4 mRNA in the odontoblast layer was highest at
      postnatal day 5, known as the advanced bell stage, when odontoblasts actively
      secrete dentin matrix proteins. Tbeta4 increased BSP mRNA and protein levels in
      MDPC-23 cells, but this was inhibited by PD98059 or SIS3 treatment. Tbeta4
      increased levels of phosphorylated (p) extracellular signal-regulated kinase
      (ERK)1/2, pSmad3, pbeta-catenin, and runt-related transcription factor 2 (Runx2)
      protein, but these effects were inhibited by PD98059 or SIS3. Tbeta4 induced the
      nuclear translocation of Runx2 and pSmad3, while nuclear translocation of beta
      catenin was decreased. Tbeta4 significantly increased BSP promoter activity,
      which was decreased by PD98059 or SIS3 treatment. Tbeta4 induced BSP expression
      in MDPC-23 cells via ERK and Smad3 signaling pathways, suggesting its role as a
      signaling molecule in odontoblasts for regulating BSP secretion during
      dentinogenesis.

PMID- 30226625
TI  - [Functional somatic symptoms - a large patient group in need of biopsychosocial
      competencies].
AB  - Functional somatic symptoms are symptoms that cannot be attributed to any known,
      well-defined physical disease, but may be very disabling for the patient.
      Functional symptoms may arise from almost any part of the body and they are
      common in practically all areas of medicine. Arranging the care for these
      patients poses a substantial challenge for many professionals, with a great
      degree of distress for the patients and costs for the health care system. A
      biopsychosocial approach is needed to understand the complex mechanisms involved.
      There are several evidence-based treatment methods for these disorders, but in
      Sweden, they have not yet been put into practice on a larger scale. The TERM
      model, as well as other models, has been developed for practitioners to help the
      patient to change focus, and engage in treatment options better suited for their
      condition. Consultation-liaison psychiatry is considered an important part of the
      health care provided for these patients.

PMID- 30226624
TI  - A novel clinical multidimensional transcriptome signature predicts prognosis in
      bladder cancer.
AB  - A number of studies has shown that long non-coding RNAs (lncRNAs), microRNAs
      (miRNAs) and protein coding genes (PCGs) are involved in various
      pathophysiological processes and can be used as prognostic biomarkers in cancer
      patients. The purpose of this study was to find a multidimensional transcriptome
      signature to predict clinical outcomes in bladder cancer. Using Cox's
      proportional hazards regression analysis and the random survival forest
      algorithm, we mined the expression profile data of 239 bladder cancer patients
      derived from The Cancer Genome Atlas (TCGA) public database. A signature
      comprised of two PCGs (ACADS and C1QTNF9B), two lncRNAs (RP11-60L3.1 and CTD
      3195I5.3) and two microRNAs (has-miR-3913-1 and has-miR-891a) with highest
      accuracy prediction (AUC=0.79 in the training dataset and 0.64 in the test
      dataset) was selected. The signature had an ability to stratify patients into
      high- and low-risk groups with significantly different survival rates (median
      16.9 vs. 54.9 months, log-rank test P<0.001) in the training dataset, and its
      performance was validated for risk stratification in the test dataset (median
      18.2 vs. 58.9 months, log-rank test P=0.002). Multivariable Cox regression
      analysis revealed that the signature was an independent prognostic factor for
      patients with bladder urothelial carcinoma (BLCA). A comparison of tumour node
      metastasis (TNM) stage and the signature indicated that the signature had better
      survival prediction power (AUCsignature=0.79/0.64 vs. AUCTNM=0.67/0.60, P<0.05).
      Functional analyses indicated that these prognostic genes from the signature may
      be involved in tumourigenesis-related biological processes and pathways. In
      conclusion, the multidimensional PCG-lncRNA-microRNA signature can be a novel
      prognostic marker to predict the survival of bladder cancer patients.

PMID- 30226626
TI  - [A national project for validation of the Collaborative Care Model in Swedish
      health care setting is planned].
AB  - One third of all persons attending primary care present mental health issues, and
      psychiatric diagnoses accounts for 45 % of sick pay in Sweden. It is important
      that cooperation between primary care and specialized psychiatry units function
      seamlessly, ensuring patients with mental disorders health care on an adequate
      level. The cooperation between primary care and specialized psychiatry must
      become more patient focused, effective and safe. There is an evidence based model
      for cooperation between primary care and specialized psychiatry not yet tried out
      in Sweden, the Collaborative Care Model. A national project for validation of the
      Collaborative Care Model in a Swedish health care setting is planned to be
      launched by initiative of the Swedish Association of Local Authorities and
      Regions.

PMID- 30226627
TI  - ?

PMID- 30226628
TI  - [ARFID: food restriction without fear of weight gain].
AB  - Avoidant/restrictive food avoidance disorder, or ARFID, is characterized by
      restrictive eating or avoidance of food in the absence of the cognitive restraint
      and weight phobia typically seen in anorexia nervosa. It is often based on a
      general disinterest in eating, selective eating due to sensory preferences,
      and/or fear of adverse consequences such as choking, although the diagnostic
      criteria allow for a number of other clinical presentations. Patients with ARFID
      tend to be younger, more often male, and have a longer duration of illness
      compared to patients with other eating disorders. Delimitation from other
      disorders affecting food intake can sometimes be problematic. Established
      specialized treatment models for restrictive eating disorders such as anorexia
      nervosa appears to be potentially effective in ARFID as well, but prospective
      treatment studies are much needed.

PMID- 30226629
TI  - ?

PMID- 30226630
TI  - [A Swedish example of integrated perinatal mental health care].
AB  - Mental disorders are common during the perinatal period and expose mother and
      child to major risks.  Almost all women in Sweden attend maternal and child
      health care centers regularly before and after birth. This constitutes a unique
      opportunity to detect women with early signs of mental disorder or at risk of
      recurrence of prior illness. Identified women need fast access to diagnostic and
      treatment providers with specialized knowledge on perinatal mental disorders. As
      perinatal mental disorders can have severe consequences for mothers and their
      children a tight cooperation between caregivers is often needed.

PMID- 30226632
TI  - ?

PMID- 30226631
TI  - [Multi-professional epilepsy teams including psychiatric expertise].
AB  - Epilepsy has a diverse spectrum of consequences that can necessitate multi
      professional cooperation in order to guarantee a high level of care. Psychiatric
      comorbidity is common, which influences quality of life, seizure control and
      mortality. Multi-professional teams, with participation from neurology,
      psychiatry, psychology, occupational therapy and social work, can together tailor
      the individual care for patients with complex needs. Close cooperation among team
      members increases quality and efficiency of care and reassurance for patients and
      their relatives while decreasing the work load for individual team members.

PMID- 30226633
TI  - [Increased somatic morbidity in patients with severe mental illness].
AB  - Patients with severe mental illness suffer an increased somatic mortality and
      morbidity from cardiovascular disease, diabetes and cancer. Furthermore, they are
      less likely to have adequate diagnostic and therapeutic procedures for somatic
      disorders. Life style issues, side effects of pharmacotherapy, cognitive
      impairment and suboptimal organization of the health care system all contribute.
      In total, a challenging situation that has to be addressed by the health care
      system. In Region Vastra Gotaland, Sweden, new medical routines for psychiatric
      patients are currently implemented. All patients should be offered an annual
      medical somatic checkup, including blood tests and ECG, and be advised about
      their life style, i.e. diet, exercise, smoking and alcohol. At the Department of
      psychosis, Sahlgrenska University Hospital, Goteborg, Sweden, a new permanent
      position as senior consultant in internal medicine/liaison physician has been
      established.

PMID- 30226634
TI  - [Consultation-liaison psychiatry - steps towards integration of physical and
      mental health care].
AB  - The evidence for the clinical and economical effectiveness of consultation
      liaison psychiatry has increased considerably in recent years. However, the
      development of consultation-liaison psychiatry services in Sweden is lagging
      behind other countries. Therefore, this article outlines the current state of
      service development, the potentials of consultation-liaison psychiatry, and the
      prerequisites for change. Politicians, commissioners and important stakeholders
      have to realize the potential of a better integration of psychological and
      physical medicine if the vision of a person-centred and equal care is going to be
      realised.

PMID- 30226635
TI  - ?

PMID- 30226636
TI  - The dual-mode dipole: A new array element for 7T body imaging with reduced SAR.
AB  - PURPOSE: To design and test an RF-coil based on two orthogonal eigenmodes in a
      pair of coupled dipoles, for 7 Tesla body imaging with improved SAR, called dual
      mode dipole. METHODS: The proposed coil consists of two dipoles and creates two
      orthogonal field distributions in a sample (the even and odd modes). A coupler
      used to excite the modes was miniaturized with the conductor track routing
      technique. Numerical simulations of the dual-mode dipole in the presence of a
      homogeneous phantom were performed. Moreover, an array of such coils was
      simulated with a voxel body model. For comparison, a fractionated dipole combined
      with a surface loop coil was also simulated. Both coils were tested in a 7 Tesla
      MRI system on a phantom. Subsequently four dual-mode dipoles or dipole/loop
      combinations were used for a comparison of imaging performance in a human
      volunteer. RESULTS: Using the even mode of the dual-mode dipole showed 70% SAR
      reduction in comparison to the fractionated dipole while having the same 
      CONCLUSIONS: It was demonstrated that the array of dual-mode dipoles provided the
      same SNR and prostate imaging quality as the reference array, while demonstrating
      lower SAR. This is due to a smoother current distribution over a sample surface.

PMID- 30226637
TI  - A human cerebral and cerebellar 8-channel transceive RF dipole coil array at 7T.
AB  - PURPOSE: Dipole antennas that provide high transmit field penetration with large
      coverage, and their use in a parallel transmit setup, may be advantageous in
      minimizing B  METHODS: A coil array was modeled with seven dipoles: six placed
      covering the occipital and temporal lobes; one covering the parietal lobe; and
      two loops covering the frontal lobe. Center-shortened and fractionated dipoles
      were simulated for the array configuration and assessed with respect to B 
      RESULTS: In simulations, the dipole arrays showed comparable performances to
      cover the whole-brain. However, for ease of construction, the center-shortened
      dipole was favored. High spatial resolution anatomical images of the human brain
      with the coil array demonstrated a full coverage of the cerebral cortex and
      cerebellum. CONCLUSIONS: The 8-channel center-shortened dipoles and frontal loops
      coil array promises remarkable efficiency in highly challenging regions as the
      cerebellum, and phase-only RF shimming of whole-brain could greatly benefit ultra
      high field magnetic resonance imaging of the human brain at 7T.

PMID- 30226639
TI  - Investigation of low molecular weight peptides (<1 kDa) in chicken meat and their
      contribution to meat flavor formation.
AB  - BACKGROUND: Low molecular weight peptides (LMWPs) (<1 kDa) generated in meat
      during chilled conditioning can act as flavor precursors in the Maillard reaction
      with a potential contribution to key volatile organic compound (VOC) formation
      upon heating. Liquid chromatography/quadrupole time-of-flight mass spectrometry
      (LC/QTOF-MS) successfully detected 44 LMWPs in chicken breast and thigh muscles
      stored at 4  degrees C for up to 6 days. Carnosine (350 mg per 100 g),
      glutathione (GSH, 20 mg per 100 g) (concentrations based on reported values in
      the literature) and cysteine glycine (Cys Gly, 5 mg per 100 g) (concentration
      based on results from LC/QTOF-MS) were used in model systems containing ribose
      (25 mg per 100 g). The three model systems were heated at 180  degrees C for 2 h
      at pH 6.3. VOCs were measured by simultaneous distillation solvent extraction/gas
      chromatography/mass spectrometry. RESULTS: Of 33 VOCs detected, 26 were
      significantly different (P <= 0.05) between the three peptides. The majority of
      nitrogen-containing volatiles, pyrazines and pyridines, dominated the carnosine
      mixture, while sulfur-containing VOCs dominated the GSH and Cys Gly peptide
      mixtures. CONCLUSION: Known key aroma compounds such as thiazole (meaty), 2
      methyl-3-furanthiol (beef and meat), 2-furfurylthiol (roasted), dihydro-2-methyl
      3(2H)-thiophenone (meaty), 2-acetylthiazole (meaty and roasted) and pyrazine
      (meaty) were detected under conditions specific to aged and thermally treated
      chicken, suggesting a potential contribution to the overall sensory quality of
      cooked meat. (c) 2018 Society of Chemical Industry.

PMID- 30226638
TI  - Impaired neutrophil extracellular traps and inflammatory responses in the
      peritoneal fluid of patients with liver cirrhosis.
AB  - Liver cirrhosis (LC) is an inflammatory process associated with impaired
      functions in adaptive and innate immune responses at both systemic and local
      levels, also referred as Cirrhosis-Associated Immune Dysfunction. In this study,
      we evaluated the functionality of neutrophils from ascitic fluid (AF) of patients
      with hepatic cirrhosis by testing their ability to generate neutrophil
      extracellular traps (NETs) in vitro. To further determine the activation state of
      neutrophils, expression of the activation markers CD66b, CD69, and CD80 on these
      cells was analysed by flow cytometry. The inflammatory environment in AF was
      assessed by measured concentration of pro- and anti-inflammatory cytokines.
      Samples were collected from 40 patients with LC, 20 of them with uncomplicated
      ascites (ASC) and 20 with spontaneous bacterial peritonitis (SBP). Peripheral
      blood (PB) neutrophils from healthy individuals were used as control (HC). Our
      results revealed a significant decrease in the release of NETs in neutrophils
      from the SBP group compared with HC. Low expression of CD69 and CD80 on
      neutrophils from AF of SBP patients was also observed. Comparisons of
      inflammatory cytokine levels in AF from the different study groups (SBP and ASC)
      revealed significant differences. In conclusion, we demonstrate that the
      development of complications, such as SBP, increases initially the inflammatory
      status, but chronically results in impaired neutrophil function as demonstrated
      by the decreased capability of NETs formation. There is also an increase in both
      pro-inflammatory and anti-inflammatory cytokines, thus predisposing for new
      episodes of SPB and increasing morbidity and mortality in cirrhotic patients.

PMID- 30226640
TI  - Evaluating green tea quality based on multisensor data fusion combining
      hyperspectral imaging and olfactory visualization systems.
AB  - BACKGROUND: The instrumental evaluation of tea quality using digital sensors
      instead of human panel tests has attracted much attention globally. However,
      individual sensors do not meet the requirements of discriminant accuracy as a
      result of incomprehensive sensor information. Considering the major factors in
      the sensory evaluation of tea, the study integrated multisensor information,
      including spectral, image and olfaction feature information. RESULTS: To
      investigate spectral and image information obtained from hyperspectral
      spectrometers of different bands, principal components analysis was used for
      dimension reduction and different types of supervised learning algorithms (linear
      discriminant analysis, K-nearest neighbour and support vector machine ) were
      selected for comparison. Spectral feature information in the near infrared region
      and image feature information in the visible-near infrared/near infrared region
      achieved greater accuracy for classification. The results indicated that a
      support vector machine outperformed other methods with respect to multisensor
      data fusion, which improved the accuracy of evaluating green tea quality compared
      to using individual sensor data. The overall accuracy of the calibration set
      increased from 75% using optimal single sensor information to 92% using
      multisensor information, and the overall accuracy of the prediction set increased
      from 78% to 92%. CONCLUSION: Overall, it can be concluded that multisensory data
      accurately identify six grades of tea. (c) 2018 Society of Chemical Industry.

PMID- 30226641
TI  - Examining the osteological paradox: Skeletal stress in mass graves versus
      civilians at the Greek colony of Himera (Sicily).
AB  - OBJECTIVES: Bioarchaeologists interpret skeletal stress as evidence of resilience
      or frailty, where absence of lesions might result from lack of exposure to
      pathogens (i.e., good health) or extreme vulnerability (i.e., selection). We
      examine physiological stress in two skeletal series from Greek Himera: (1) nine
      mass graves from the battles of Himera (480 and 409 BCE) and (2) Himeran
      civilians (648-409 BCE). Civilians are assumed to have died from multiple causes,
      including ill health leading to their deaths. Individuals from the battles
      presumably died while in relatively good health, in battle. More skeletal stress
      among civilians than battle casualties would support the idea that skeletal
      stress is a sign of frailty at Himera. We compare variation in skeletal stress
      between and among civilians and battle casualties. MATERIALS AND METHODS: Cribra
      orbitalia, porotic hyperostosis, linear enamel hypoplasia (LEH), and sub
      periosteal new bone formation, were examined in 474 individuals (mass graves n =
      64; civilians n = 410). RESULTS: Chi-square tests showed significantly higher
      prevalence of LEH (p = 0.04) and sub-periosteal new bone formation (p = 0.05)
      among young and mid-aged adult male civilians than mass grave casualties.
      Skeletal stress was also lower in the earlier battle, and varied among civilians
      with burial style. DISCUSSION: Our findings generally support the hypothesis that
      skeletal stress is evidence of frailty (i.e., leading to greater risk of
      mortality). However, the relationship between stress and frailty is complicated
      by social factors, when considering historical context. In particular, a possible
      "soldier-class" may have experienced less stress than the overall civilian
      population.

PMID- 30226642
TI  - A Roadmap for Value-Based Payment Models among Patients with Cirrhosis.
AB  - Cirrhosis is the final common pathway for most chronic liver diseases, afflicting
      approximately 0.27% of the adult population and accounting for over 60,000 deaths
      in the U.S. each year.1,2 Although the general public perceives liver disease to
      be rare, cirrhosis-attributable mortality surpasses that from diabetes or kidney
      disease This article is protected by copyright. All rights reserved.

PMID- 30226643
TI  - The reHISS Three-Range Exchange Functional with an Optimal Variation of Hartree
      Fock and Its Use in the reHISSB-D Density Functional Theory Method.
AB  - In the present study, we have reparametrized the HISS exchange functional. The
      new "reHISS" exchange provides a balance between short- and mid-range Hartree
      Fock exchange (HFX) and a large total HFX coverage, with a fast convergence to
      zero HFX in the long range. The five parameters in this functional (according to
      equations 3 and 4 in the main text) are cSR = 0.15, cMR = 2.5279, cLR = 0,
      omegaSR = 0.27, and omegaLR = 0.2192. The combination of reHISS exchange with a
      reparametrized B97c-type correlation functional (Chan et al., J. Comput. Chem.
      2017, 38, 2307) and a D2 dispersion term (s6 = 0.6) gives the reHISSB-D method.
      We find it to be more accurate than related screened-exchange methods and,
      importantly, its accuracy is more uniform across different properties.
      Fundamentally, our analysis suggests that the good performance of the reHISS
      exchange is related to it capturing a near-optimal proportion of HFX in the range
      of interelectronic distance that is important for many chemical properties, and
      we propose this range to be approximately 1-4A. (c) 2018 Wiley Periodicals, Inc.

PMID- 30226644
TI  - Maternal condition and maternal investment during lactation in mantled howler
      monkeys.
AB  - OBJECTIVES: Lactation is a costly reproductive state for females, as it may
      entail decreased body condition, increased morbidity, and increased mortality
      risk. To offset these costs, mothers should allocate investment in infant care as
      a function of their physical condition. Here, we assessed the relationship
      between maternal condition and maternal investment in wild mantled howler monkeys
      (Alouatta palliata) to determine: (1) whether maternal physical condition varied
      as a function of food availability, activity levels and feeding effort throughout
      lactation; (2) whether maternal investment was affected by maternal condition and
      offspring age. MATERIALS AND METHODS: We studied six adult females while rearing
      their immature offspring. We determined weekly food availability, C-peptide
      levels (as a measure of energy balance) in urine samples (306 samples), mothers'
      time budgets, feeding rates, time spent vigilant, and time spent carrying their
      offspring (for two years; 600 observation hours). RESULTS: C-peptide levels were
      positively related to food availability. Maternal care in terms of vigilance and
      offspring carrying peaked at early lactation and decreased progressively with
      offspring age. Carrying was positively related to C-peptide levels and was also
      influenced by variation in maternal condition throughout lactation. DISCUSSION:
      These results converge with previous theoretical and empirical studies on this
      topic and contribute to the growing evidence that nonhuman primate mothers
      allocate maternal care based on their current condition to maximize lifetime
      reproductive success.

PMID- 30226645
TI  - The monocyte locomotion inhibitory factor inhibits the expression of inflammation
      induced cytokines following experimental contusion in rat tibia.
AB  - Entamoeba histolityca produces the monocyte locomotion inhibitory factor (MLIF),
      a pentapeptide with powerful anti-inflammatory properties. MLIF may regulate
      trauma-induced inflammation through the effects it exerts directly or indirectly
      on immune cells, modulating the production and/or expression of the cytokines
      involved in the inflammatory processes that occur after damage. The aim of the
      present study was to evaluate the effect of MLIF on production of pro/anti
      inflammatory cytokines after contusion in the rat tibia. Fifty-four Wistar rats
      were subjected to controlled contusion with a special guillotine-type device, and
      36 rats were injected with MLIF or tenoxicam into the tibia. Eighteen animals
      received saline; the animals were sacrificed 24 or 48 hours after injection.
      Cytokine mRNA and protein production were determined by reverse transcriptase
      polymerase chain reaction (RT-PCR), immunofluorescence, and hematoxylin-eosin
      staining was performed to visualize cellular infiltration in the rats' injured
      tissue. Expression levels of the cytokines interferon gamma (IFN-gamma), tumour
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and transforming growth
      factor-beta (TGF-beta) mRNA were inhibited significantly by MLIF at 24 hours post
      contusion. MLIF significantly increased the expression levels of IL-10 at 24
      hours compared with tenoxicam or the control group. These changes were associated
      with a significant decrease in protein production levels of TNF-alpha, IFN-gamma,
      IL-6 and TGF-beta at 24 hours. Histological evaluation showed the presence of
      infiltration by neutrophils, monocytes and leucocytes in control tissues. This
      infiltration was decreased after MLIF administration, and intense infiltration
      was observed in tenoxicam-treated group. MLIF inhibited the expression of pro
      inflammatory cytokines and increased the expression of anti-inflammatory cytokine
      IL-10.

PMID- 30226646
TI  - From protectionism to inclusion: A New Zealand perspective on health-related
      research involving adults incapable of giving informed consent.
AB  - The revision of the Council of International Organizations of Medical Sciences
      (CIOMS) International ethical guidelines for health-related research (2016)
      heralds a paradigm shift from the 'protectionist' policies that emerged following
      historical research atrocities of the 20th century, towards a more nuanced and
      inclusive approach to research participation. Adopting this modified approach
      will enable countries to secure the benefits of research for individuals and for
      society as a whole, while at the same time minimizing the potential for
      exploitation and research-related harms. This article considers the potential
      impact of Guideline 16 of the CIOMS 2016 from a New Zealand perspective, with
      respect to research involving adults with impaired capacity and who are incapable
      of giving informed consent. While the CIOMS 2016 apply a 'minimal risk' threshold
      to guide research involving adults who lack capacity to consent, New Zealand law
      currently adopts a 'best interests' standard which significantly restricts the
      scope of permissible research that may be performed in this context. This article
      argues that the CIOMS 2016 should influence change to New Zealand's legal
      framework for ethical review of research. CIOMS 2016 provides useful guidance for
      the necessary standards and processes to enable the responsible and ethical
      inclusion of adults with impaired capacity in research.

PMID- 30226647
TI  - Computational Feasibility of an Exhaustive Search of Side-Chain Conformations in
      Protein-Protein Docking.
AB  - Protein-protein docking procedures typically perform the global scan of the
      proteins relative positions, followed by the local refinement of the putative
      matches. Because of the size of the search space, the global scan is usually
      implemented as rigid-body search, using computationally inexpensive
      intermolecular energy approximations. An adequate refinement has to take into
      account structural flexibility. Since the refinement performs conformational
      search of the interacting proteins, it is extremely computationally challenging,
      given the enormous amount of the internal degrees of freedom. Different
      approaches limit the search space by restricting the search to the side chains,
      rotameric states, coarse-grained structure representation, principal normal
      modes, and so on. Still, even with the approximations, the refinement presents an
      extreme computational challenge due to the very large number of the remaining
      degrees of freedom. Given the complexity of the search space, the advantage of
      the exhaustive search is obvious. The obstacle to such search is computational
      feasibility. However, the growing computational power of modern computers,
      especially due to the increasing utilization of Graphics Processing Unit (GPU)
      with large amount of specialized computing cores, extends the ranges of
      applicability of the brute-force search methods. This proof-of-concept study
      demonstrates computational feasibility of an exhaustive search of side-chain
      conformations in protein pocking. The procedure, implemented on the GPU
      architecture, was used to generate the optimal conformations in a large
      representative set of protein-protein complexes. (c) 2018 Wiley Periodicals, Inc.

PMID- 30226649
TI  - Functional and structural properties of red color-related pigment-binding protein
      from the shell of Litopenaeus vannamei.
AB  - BACKGROUND: A novel red color-related pigment-binding protein named LvPBP75
      isolated from the shell of Litopenaeus vannamei has recently been identified as
      hemocyanin. However, information on the functional and structural properties of
      LvPBP75 is insufficient. This study aimed to elucidate the thermal properties and
      pigment-binding ability of LvPBP75. RESULTS: LvPBP75 showed significant red color
      change after heat treatment with high concentrations of NaCl (>0.1 mol L-1 ),
      acidic (<5) or alkaline (>9) pH values and alcohols. LvPBP75 mRNA expression
      analysis revealed that expression level was highest in hepatopancreas and weakest
      in muscle. Reconstruction and structural analysis revealed that astaxanthin could
      bind to hemocyanin derived from the shell of L. vannamei but not to hemocyanins
      derived from the hepatopancreas or hemolymph of other invertebrates. Three
      dimensional models of hemocyanin monomer displayed significant structural
      differences between native LvPBP75 and hemocyanin derived from shrimp
      hepatopancreas. CONCLUSION: The results suggest a novel function of hemocyanin as
      binding with pigment and its involvement in L. vannamei shell color change. The
      pigment-binding ability of hemocyanins has species and tissue specificity, and
      their unique structural features play an important role in binding ability. (c)
      2018 Society of Chemical Industry.

PMID- 30226650
TI  - Quantum Master Equation Approach to Singlet Fission Dynamics in Pentacene Linear
      Aggregate Models: Size Dependences of Excitonic Coupling Effects.
AB  - The singlet fission (SF) dynamics of pentacene linear aggregate models are
      investigated using the quantum master equation method by focusing on the Frenkel
      excitonic (FE) coupling effects on the SF rate and double triplet (TT) yield as
      well as on their aggregate size dependences. It is found that for the dimer
      model, unrealistically large FE couplings are needed to provide significant
      effects on the SF dynamics, while for the larger aggregate models a realistic FE
      coupling causes significant variations in the SF dynamics: as increasing the
      aggregate size, the SF rate rapidly increases, attains the maximum at 8-mer (~3
      times enhancement as compared to the non-FE-coupling case) and then decreases,
      approaching a stationary value after 12-mer, although the stationary TT yield at
      20-mer remains slightly smaller than that in the non-FE-coupling case. These
      features are explained based on the relative relaxation factors between the
      adiabatic exciton states. The present results contribute to constructing the
      design guidelines for highly efficient SF aggregates. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 30226651
TI  - A subgroup analysis to compare patients with acute low back pain classified as
      per treatment-based classification.
AB  - OBJECTIVES: The evidence for the effectiveness of interventions targeting acute
      low back pain (LBP) is suboptimal. It is difficult to identify those patients who
      are more likely to develop chronic pain and disability after an acute episode of
      LBP. These shortcomings may be attributed to considering LBP as one homogenous
      condition. METHODS: In this quasi-experimental study, we examined and analysed a
      prospective cohort of 267 patients with first-onset LBP and classified them into
      one of the groups based on treatment-based classification: direction-specified
      exercises (Group 2), manipulation (Group 3), stabilization exercises (Group 4),
      traction (Group 5), and a physician care group (Group 1). Disability and pain
      were assessed at baseline, after treatment, and at 6 months using the Oswestry
      Disability Index and the Numerical Rating Scale, respectively. Comparisons were
      made between the groups, and we predicted measures of disability and pain
      intensity at 6 months with age, gender, fear avoidance behaviour, centralization
      phenomenon (CP), expectations about recovery, CP, group classification, baseline
      pain, and disability. RESULTS: Analysis showed that all the heterogeneous groups
      of LBP improved their outcomes with the respective treatment provided. However,
      when the entire sample was considered as one homogenous group of LBP, the results
      showed improvement with time (p < 0.05) only and no difference was found between
      groups (p > 0.05). None of the studied factors, except baseline pain (R = 0.227,
      R2  = 0.051, p < 0.05), were able to accurately predict the development of
      chronic pain in our study sample. CONCLUSION: Though our results showed no
      differences between the subgroups in the reduction of pain and disability, we
      conclude that classifying and treating patients with LBP into subgroups based on
      signs and symptoms produce better outcomes. Baseline pain alone may predict a
      small percentage of people who may develop chronic pain.

PMID- 30226652
TI  - Periodic expression of cell-cycle regulators: A laboratory experiment proposal
      for students in molecular and cell biology.
AB  - This article describes a laboratory exercise designed for undergraduate students
      in the subject of "Regulation of cell proliferation" which allows the students to
      carry out a research experiment in an important field such as cell cycle control,
      and to be introduced to a widely used technique in molecular biology laboratories
      such as the western blot. The cell cycle is regulated by the succession of cyclin
      CDK kinase activities. Activation and inactivation of different cyclin-CDK
      complexes depend on the control of their positive and negative regulators,
      cyclins and CDK inhibitors (CKIs), respectively. In this experiment, fluctuations
      in the level of mitotic cyclin Clb2 and CDK inhibitor Sic1 throughout the cell
      cycle of Saccharomyces cerevisiae are analyzed, particularly in the context of
      the control of mitotic exit and Start, two of the most important cell cycle
      transitions. In order to do this, a cdc15 mutant strain is used to block cells in
      telophase and, upon release from this blocking, the variation in the levels of
      Clb2 and Sic1 proteins are analyzed by western blot. Progress along the cell
      cycle is also evaluated by microscopic analysis of cell morphology and nuclear
      staining. This practical illustrates the experimental basis of theoretical
      concepts worked in the classroom and it is a good framework for an in-depth
      discussion of these concepts based on experimental data analysis. (c) 2018
      International Union of Biochemistry and Molecular Biology, 46(5):527-535, 2018.

PMID- 30226653
TI  - ?

PMID- 30226654
TI  - [Arterial hypotension: behind the scenes].
AB  - Arterial hypotension is a frequently encountered phenomenon in clinical practice.
      It is responsible for multiple consultations and/or hospitalizations, mostly in
      elderly people. It is associated with an increased morbidity and mortality.
      Arterial hypotension can be constitutional, part of a syndrome, orthostatic, or
      secondary (drug induced, hypovolemia). The diagnosis can be done by measuring the
      blood pressure in the supine position, sitting and standing position, and by 24h
      ambulatory blood pressure monitoring. The first line of treatment is non-drug
      therapies . The most frequently used medical treatments are midodrine, and
      fludrocortisone. However specific molecules as droxidopa, pyridostigmine,
      erythropoietin can also sometimes be indicated.

PMID- 30226655
TI  - [Benefits of meditation on the hypertensive adult].
AB  - The prevalence of high blood pressure is increasing and expanding preventive and
      treatment measures may be useful. Some data in the literature suggest that
      meditation can play a role not only in stress management but also in blood
      pressure control and cardiovascular disease prevention. Mechanisms involved may
      be based on the regulation of emotional and biological responses to stress, by
      regulation of the autonomous nervous system. This approach is available to
      everyone interested, has no adverse effects and is not related to any particular
      religious beliefs.

PMID- 30226656
TI  - [American guidelines under high pressure !]
AB  - International guidelines on definitions, therapeutic targets and treatment of
      arterial hypertension are regularly published by national and international
      societies in order to help medical doctors to optimally screen and take charge of
      their patients and to apply the best evidence based medicine. Hypertension
      remains a major cause of mortality worldwide and is insufficiently well
      controlled. We present here the new 2017 American guidelines that harbor major
      changes compared with the previous ones. Even if the new 2017 American
      definitions and therapeutic targets will not be applied in Europe and Switzerland
      and perhaps even in United States, it is good to know them even if only to
      correctly follow medical literature and avoid a certain confusion in managing
      high blood pressure.

PMID- 30226657
TI  - [Hypertension management : from medical inertia to patient autonomy].
AB  - The percentage of patients treated for hypertension with a well-controlled blood
      pressure (< 140/90 mmHg) remains disappointedly low, in general way below 50 %,
      despite all national and international recommendations. Among the causes
      explaining this insufficient control, therapeutic inertia has been identified as
      an important determinant, which unfortunately did not improve over the last 10-20
      years. Patients' empowerment through home blood pressure monitoring and perhaps
      self-titration according to a well pre-specified scheme supported by telemedicine
      could represent news avenues to fight against therapeutic inertia.

PMID- 30226658
TI  - [Isolated diastolic hypertension : do we still have to care about it ?]
AB  - Isolated diastolic hypertension (IDH), defined as a diastolic blood pressure
      (DBP) > 90 mmHg and a systolic blood pressure (SBP) < 140 mmHg, is a common
      situation in medical practice. In the elderly, the cardiovascular risk is clearly
      associated with the level of systolic BP and pulse pressure. However, diastolic
      BP is also associated with an increased risk of cardiovascular event, in
      particular among young hypertensive patients (< 50 years old). Therefore,
      isolated diastolic hypertension should not be neglected. A careful follow-up of
      patients with IDH should be put in place with lifestyle changes. Sometimes, a
      pharmacological treatment must be started to control DBP.

PMID- 30226660
TI  - ?

PMID- 30226659
TI  - [Chlamydial infections : epidemiology, pathogenesis, diagnosis and treatments].
AB  - Chlamydiae are a heterogeneous group of strict intracellular bacteria. Chlamydia
      trachomatis is the most common cause of sexually transmitted bacterial infection.
      Being generally asymptomatic, C. trachomatis infections are a major cause of
      tubar infertility and extra-uterine pregnancy. C. pneumoniae may cause asthmatic
      bronchitis. C. psittaci infections, although usually developped after exposure to
      infected birds, has recently been documented following exposure to infected
      horses. Waddlia chondrophila is an emerging human pathogen of miscarriage.
      Parachlamydia acanthamoebae, Protochlamydia naeglerophila and to a lesser extent
      Simkania negevensis, have been associated with lower respiratory tract
      infections.

PMID- 30226661
TI  - ?

PMID- 30226663
TI  - ?

PMID- 30226662
TI  - ?

PMID- 30226664
TI  - ?

PMID- 30226665
TI  - ?

PMID- 30226666
TI  - ?

PMID- 30226667
TI  - [A relational approach to partnership between patients and professionals : design
      and implementation].
AB  - To implement an institutional culture of the partnership, the University
      Hospitals of Geneva (HUG) first studied existing collaborations between patients
      and professionals. The engaged professionals, their positions, and patient
      involvement form the structure of the relational approach. This approach relies
      on a foundation of consideration for others, their expertise and mutual respect.
      The Patient Partners Platform networks partners and their actions, supports
      initiatives and educates about partnership. Exchanges between patients and
      healthcare professionals are sustained (67 meetings and 510 patient involvements
      in 2 years) ; each party reaps benefits. This implementation strategy facilitates
      partner involvement, encourages partnership and is easily transferable to all
      healthcare institutions.

PMID- 30226668
TI  - [InfoKids: changing the patients' journey paradigm in an Emergency Department].
AB  - Nowadays, citizens are little supported to decide whether they should consult the
      Emergency Departments (ED) in case of illness or trauma. Moreover, once in the
      ED, they often must deal with overcrowding, long waiting times, the acute nature
      of the visits, administrative data management, and a lack of follow-up after the
      visit. To improve this situation, we have developed an e-health solution
      delivering a more patient-centered experience by connecting patients, caregivers,
      and administrative clerks through a web and mobile applications. This innovative
      system is intended to improve the entire emergency care process, facilitating the
      caregiver and administrative work and supporting patients before, during, and
      after their ED consultation.

PMID- 30226669
TI  - [Moving towards patient-centered care using a mobile application : the Concerto
      project].
AB  - The benefits of patient empowerment are more and more recognized, and digital
      technologies have an important potential to favor it. The mobile application
      Concerto, prototyped during a hackathon, was co-created by caregivers, developers
      and patients by using a user-centered design and an agile development
      methodology. It uses the information available in the hospital information system
      to provide patients with an up-to-date schedule of care, targeted medical and
      practical information, a presentation of the care team and a tool promoting
      interactions with caregivers. The project is currently in experimental phase in 4
      care units, and regularly improved through continuous evaluation and integration
      of new modules.

PMID- 30226670
TI  - [" More time for patients " : a reorganization of medical wards at the University
      Hospitals of Geneva].
AB  - The University Hospitals of Geneva initiated their latest strategic plan by
      consulting widely with employees and patients. Nine main avenues were defined as
      priority projects for the institution. The project " More time for patients "
      aims at simplifying clinical and administrative processes using tools from Lean
      management and Design Thinking. Its objectives are to redefine the organization
      of the healthcare-related tasks in order to optimize the time spent with patients
      and relatives, increase patients' involvement and shared decision making, and
      improve both the communication with patients, as well as the interdisciplinary
      collaboration, with patients always at the heart of care.

PMID- 30226671
TI  - [Real-time tele-training for obstetrical ultrasonography in Congo Brazzaville].
AB  - The Republic of Congo is facing a shortage of specialists and an unequal
      distribution of healthcare professionals between urban and rural areas, limiting
      access to diagnostic ultrasonography. Besides other issues this project aims at
      establishing the feasibility of remote training by live teleconsultation in
      obstetrical ultrasonography, as a mechanism to support isolated care by untrained
      staff. The project includes abdominal ultrasound testing for women during all
      stages of pregnancy. The first results have shown that the transmission of
      dynamic images, at a low cost internet connection, offers the possibility of
      distance training of peripheral health professionals, with the real-time remote
      support of gynecologists.

PMID- 30226672
TI  - [Bigdata, artificial intelligence and blockchain for dummies].
AB  - Digitalization is transforming every aspect of life, it is also transforming
      deeply medicine. The digitalization era is characterized by a large production of
      new data streams while existing processes are progressively migrated, such as
      writing or imaging. The very large and fast-growing amount of data available
      requires new storage, transport and analytical tools. This paper presents some of
      them, such as natural language processing, artificial intelligence, and graph
      databases. A short introduction to the technology of blockchain is also provided,
      as it is increasingly used in some non-monetary transaction in medicine, such as
      data exchanges and consent management.

PMID- 30226673
TI  - [" Doctor, my child swallowed water, can he die from dry drowning ? " An update
      on drowning in 2018].
AB  - Drowning is a significant and neglected public health problem mostly affecting
      young children. The definition of drowning has recently been modified and the
      notions of " dry drowning ", " secondary drowning " and " near drowning " are no
      longer accepted or used. However, recent articles in the media describing dry
      drowning of children have been reported. This entity seems to be absent of the
      actual scientific literature and worried parents can be reassured. Increased
      vigilance is the key as prevention is the most efficient intervention to reduce
      drowning mortality. To provide more guidance to the pediatrician and the general
      practitioner we are reviewing the most recent literature on the subject, as well
      as facts in the mater of drowning prevention.

PMID- 30226674
TI  - ?

PMID- 30226676
TI  - ?

PMID- 30226675
TI  - ?

PMID- 30226677
TI  - ?

PMID- 30226678
TI  - ?

PMID- 30226679
TI  - ?

PMID- 30226680
TI  - Letter to the Editor: Perspective of Sensory Ataxia in Leprosy.

PMID- 30226681
TI  - 19th International Leprosy Congress: the Plenary Sessions.

PMID- 30226682
TI  - From the new ILA President.

PMID- 30226683
TI  - [Multifractal Analysis of Rapeseed Spectrum for Chlorophyll Diagnosis Modeling].
AB  - One of the most important topics in crop information science is how to make use
      of the crop's information for non-destructive nutrient diagnosis which can be
      solved with spectrum analysis. The canopy's spectrum feature is a key indicator
      to describe the nutritional status for the rapeseeds. The original spectrum is to
      be disturbed with external factors such as environment and climate; however, it
      is difficult to be directly used for rapeseed biomass diagnosis due to its huge
      fluctuation. However, the multifractal feature of the spectra remains stable
      relatively. In order to study the relationship between the canopy's spectrum of
      the rapeseed and its chlorophyll, based on the multifractal theory, a
      quantitative model of chlorophyll prediction and a qualitative model of planting
      pattern identification were proposed in this paper to study the high oleic acid
      rapeseed samples in 24 transplanting regions and 24 direct planting regions. At
      first, the generalized Hurst exponent and mass exponents together with other
      relevant multifractal parameters of the spectra were extracted with popular
      multifractal detrended fluctuation analysis (MF-DFA) in different six considered
      wavelength ranges. It shows that all of them possess representative multifractal
      nature. However, there are some differences of the multifractal characteristics
      between the two kinds of regions with different planting pattern in some bands.
      In addition, by correlation analysis and detection between the multifractal
      parameters of the spectra and the SPAD values in six considered ranges of bands,
      it demonstrates that there is some difference of the effective information
      content in the different ranges of bands. In the quantitative model of
      chlorophyll prediction, for each groups of samples in transplanting regions and
      direct planting regions and mixed together in each significant bands, a selected
      multifractal parameter was used to establish the univariate model for predicting
      the rapeseed leaf's SPAD values, respectively. The results of all the relative
      root mean square errors are small than 5%. Finally, the qualitative model was
      proposed to distinguish the samples by the two planting pattern. Youden index, as
      the identification accuracy was calculated for the six considered ranges of bands
      by the Fisher's linear discriminant analysis. The best Youden index is 0.902 5
      and the corresponding band range is 350~1 350 nm. The significant work provides a
      theoretical and practical method for predicting rapeseed leaf's SPAD and also
      provides effective way to find the sensitive bands of the spectra for
      identification diagnosis.

PMID- 30226684
TI  - [Influence of Light Source and Paper Color on the Exhibiting Preference of
      Traditional Calligraphy].
AB  - The Chinese calligraphy is a unique art of traditional Chinese culture. The core
      of color preference for Chinese calligraphy is figural preference, which is a
      special kind of color combination preference. Currently, the exhibition of
      calligraphy is always lack of scientific basis in the aspect of color science. In
      this research, the influence of light sources and paper color on the preference
      of traditional calligraphy was analyzed based on subjective and objective
      experiments. The relative spectral power distribution of 5 typical light sources
      (correlated color temperature: 2 500, 3 500, 4 500, 5 500 and 6 500 K) and
      spectral reflectance of 5 typical Chinese rice papers (white, orange, light
      white, red, yellow-white) were firstly measured and then transformed into CIEXYZ
      and CIECAM02 color space, respectively. Subsequently, the correlation between
      those colors attributes and 1 000 series of psychophysical experiment data from
      40 observers on calligraphy exhibiting preference was analyzed. At last, the
      influence factors of the correlation were discussed form a multiple statistical
      point of view, such as normal distribution, correlation analysis and multiple
      regression. The experimental results indicated that the exhibiting preference of
      Chinese calligraphy is obviously different with that of ordinary color preference
      cases, for it is mainly affected by the attributes of lighting sources instead of
      the contrast of hue and lightness. The authors believe that the finding of the
      research will provided effective support for the development of calligraphy
      exhibiting in near future for museums and gallaries.

PMID- 30226686
TI  - TB, AIDS: major progress

PMID- 30226685
TI  - [Quantitative Detection of Iron in Soybean Oils with Laser Induced Breakdown
      Spectroscopy and Simple Regression Methods].
AB  - LIBS (laser-induced breakdown spectroscopy) was used to detect Fe element content
      in soybean oil quantitatively. In this experiment, a series of soybean oil
      samples with different concentrations of Fe were used; LIBS spectra were
      collected with a two-channel high precision spectrometer. According to the LIBS
      spectrum of samples, two characteristic wavelength of Fe (404.58 and 406.36 nm)
      were determined, and different simple regression methods (exponential regression,
      linear regression and quadratic regression) were used to establish the
      quantitative analysis models of Fe content using each characteristic spectral
      line. The results indicate that the average relative error of Fe I 404.58 and Fe
      I 406.36 in simple exponential regression, linear regression and quadratic
      regression models were 29.49%, 8.93%, 8.70% and 28.95%, 8.63%, 8.44%,
      respectively. The results of Fe I 406.36 regression models is better than that of
      Fe I 404.58, and the quadratic regression model is optimal among the three
      regression models. According to these results, LIBS technology has certain
      feasibility for detecting Fe in soybean oil; the quadratic linear regression
      model can improve the prediction accuracy of Fe element effectively.

PMID- 30226687
TI  - [Determination of 20 Trace Elements in the Blood Collection Tubes with ICP-MS].
AB  - To investigate the contamination of blood collection tubes, 20 trace elements
      (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sn, Sb, Ba, W, Hg, Tl, Pb) in
      13 different types of blood collection tube were studied with ICP-MS method. The
      lixivium of H(2)O and 10% HNO(3) were measured with ICP-MS, and then the
      contamination coming from the blood collection tube is specified. According to
      the concentration range of human blood, plasma and serum from recently published
      literature, this report presents a detailed analysis of capable trace elements
      for each blood collection tube. The results showed that, tube No.1 is capable to
      analyze 18 trace elements in the human serum; tube No.6 is capable to analyze 15
      trace elements in the human plasma; tube No. 13 is capable to analyze 17 trace
      elements in the human blood. But we still should be aware that, the elements Sb
      and W in tube No.1, the elements V, Cr, Ni, and Sb in tube No.6, and the elements
      Al, Sb and W in tube No.13, are in the same magnitude of the normal trace element
      concentration range in the human serum, plasma and blood. They might affect the
      testing results. The serum collected from the same volunteer by tube No.1 and
      tube No.3 were compared here, the results show that, almost each trace element
      concentration of human serum from tube No.1 is lower than from tube No.3,
      especially for elements Al, V, Cr, Mn, As, Sn, and Sb. The results indicate that
      the blood collection tubes show great impact on determination of trace element.

PMID- 30226688
TI  - [A New Sample Fusion Technique for Quantitative Analysis of Major and Minor
      Elements in Sulfides with X-Ray Fluorescence Spectrometry and Laser Ablation
      Inductively Coupled Plasma Mass Spectrometry].
AB  - A new sample fusion method for sulfides has been developed in this study. HNO3
      was used as a short pre-oxidation reagent instead of the traditional solid
      oxidant (e.g., NaNO3, KNO3), which avoid the erosion of the platinum crucible.
      GeO2 was also added in samples to avoid the break of glass beads. The good
      analytical precisions of X-ray fluorescence spectrometry (RSD<5.6%, 1sigma) and
      laser ablation inductivity coupled plasma mass spectrometry (RSD<3%, 1sigma)
      demonstrated that the major elements were homogeneously distributed in the fused
      beads of sulfides. The determined major and minor elements (Si, Al, Fe, Mg, K,
      Ca, Na, Mn, Cu and Zn) values by using XRF and LA-ICP-MS are in excellent
      agreement with published values in three reference sulfide standards(reference
      values for Ti were absent). These results clearly demonstrate that the present
      fusion technique is well suitable for routine sulfide sample preparation for both
      XRF and LA-ICP-MS analysis.

PMID- 30226689
TI  - [A Hydride Generation-Catalytic Resonance Rayleigh Scattering Method for
      Detection of Trace Arsenic].
AB  - Arsenic is a toxic metal element and the establishment of a highly sensitive and
      selective method for As has great significance to human health and environment
      protection. In sulfuric acid medium, As(III) was reduced by NaBH4 to form AsH3
      gas that was trapped by the Ce(IV)-I- catalytic absorption solution to cause
      Ce(IV) concentration decreased and As particle increased, which resulted in the
      resonance Rayleigh scattering (RRS) and fluorescence increased at 370 and 351 nm
      respectively. The increased RRS and fluorescence intensities were linear to
      As(III) concentration in the range of 0.006~0.76 and 0.006~0.28 mg.L(-1)
      respectively, with a detection of As of 3.0 MUg.L(-1). The new hydride generation
      catalytic RRS method was applied for detection of trace As(III) in milk samples,
      and the results were in agreement with that of hydride generation-atomic
      absorption spectrometry.

PMID- 30226690
TI  - [Spectra and Mineralogy Study on Black Tianhuang and Kengtou Stone from Shoushan,
      Fujian Province].
AB  - Shoushan Stone is one of the national stones of our country which is also the
      most famous stone of the four outstanding seal stones in China. As to Shoushan
      stones, black Tianhuang stone is a kind of black colored stone. It is one of the
      most special species in Tianhuang stones which comes from fields beside the
      Shoushan Brook. The black Kengtou stone comes from Kengtou Zhan, its original
      place. In this study, black Tianhuang stone is studied and compared with black
      Kengtou stone by using X-ray powder diffraction spectrometer (XRD), infrared
      spectrometer (IR), laser ablation inductively coupled plasma mass spectrometry
      (LA-ICP-MS), and scanning electron microscopy (SEM) in order to analyze the
      mineral composition, characteristic of infrared spectra, color genesis, and
      characteristic of micro- morphology of these stones. The results of the study
      indicate that the mineral compositions are different between these stones. The
      analysis of IR and XRD studies indicate that the black Kengtou stone is mainly
      composed of dickite. On the other hand, XRD analysis indicates that it can
      contain a small amount of pyrophyllite, illite, pyrite, and quartz. However, the
      analysis of IR and XRD studies indicate that black Tianhuang stone is mainly
      composed of dickite or nacrite. On the other hand, XRD analysis indicates that
      the minor mineral composition in the black Kengtou stone can be svanbergite and
      tochilinite. Their characteristics of micro-morphology of black Tianhuang stone
      and black Kengtou stone are also different. The crystal size of dickite in black
      Tianhuang stone is inconformity, and the margin of lamellae crystals is smoothed.
      It indicates that such kind of stone had undergone corrosion effect due to water
      rock reaction. On the other hand, the black Kengtou stone are well crystalized.
      The lamellae has sharp margin, and the size of the lamellae is relatively
      uniform. It indicates that the black Kengtou stone is original ore. According to
      the trace chemical composition analysis of LA-ICP-MS, it preliminary suggests
      that black color of both black Tianhuang and Kengtou stones have relationship
      with Fe element. The final conclusion of color genesis needs more experiments to
      prove.

PMID- 30226691
TI  - [Spectroscopy Characterization of Anthracite Oxide].
AB  - With high degree of metamorphism and carbon content, anthracite is commonly used
      for activated carbon. The structural properties of anthracite play a decisive
      role in its materialization, while with chemical oxidation, anthracite structure
      can be purposefully improved. The anthracite oxide was prepared via acid leaching
      and oxidizing, using high carbon content and low ash content anthracite from
      Zhaotong, Yunnan Province, China. The structural and spectroscopy characteristics
      of anthracite and anthracite oxide were acquired with X-ray diffraction (XRD),
      Raman spectroscopy and attenuated total reflectance-Fourier transform infrared
      spectroscopy (ATR-FTIR). The results show that crystallites in anthracite have
      intermediate structures between graphite and amorphous. Compared with bitumite
      and lignite, its structure order degree lies between graphite and low metamorphic
      coals with relatively high average diameter of coal crystallites(La) and average
      height of coal crystallites (Lc). The process of anthracite oxidation can be
      modeled in two steps, the edge of crystal was curled and destroyed with strong
      oxidation, with the generation of CO group and intercalation of HNO3/H2SO4 into
      the edge layers, leading to the reducing of lateral sizes; HNO3/H2SO4 were
      continually intercalated into crystals, resulted in the increase of interlayer
      spacing (d(002)) from 0.351 to 0.361 nm, and the number of stacked layers dropped
      to 4.5 from 6 due to exfoliate. ID1/IG in Raman spectroscopy increased from 1.9
      to 2.0, with full width at half maximum (FWHM) of G bond and intensity of D2 bond
      increasing from 63 to 68 and 10.26 to 13.78. Numbers of new -C-O-, CO, -NO2
      groups generated, leading to the decrease of oxygen-containing functional groups
      content from 0.11 to 0.42. After HNO3/H2SO4 oxidation, the aromaticity (fa) of
      anthracite oxide increases, with the decrease of structure order degree and more
      over a lot of active reaction sites generates in the process. The oxidation of
      anthracite enables anthracite has great potential in the application of porous
      carbon preparation.

PMID- 30226692
TI  - Differences in Women Who Choose Subdermal Implants Versus Intrauterine Devices.
AB  - Objective: To determine if there are any differences in the patient populations
      that choose subdermal implants versus intrauterine devices (IUDs) for
      contraceptive purposes. Study Design: Retrospective chart review. Electronic
      medical records of women who presented to the University of Texas Medical Branch
      in Galveston's Regional Maternal Child Health Program Clinics in southeast Texas
      from March 2011 to March 2013 and received a subdermal implant or IUD were
      reviewed. Differences in characteristics of women who chose either form of
      contraception were determined. Results: A total of 356 charts were reviewed. Of
      those, 188 (53%) women chose the subdermal implant and 168 (47%) chose an IUD.
      Patients who chose subdermal implants were more likely to have had a long-acting
      reversible contraceptive (LARC) method previously (p<0.01), previous vaginal
      deliveries (p<0.001), and an interval from delivery to LARC placement of >1 year
      (p<0.001). LARC choice was race-specific in that, when compared to Caucasian
      women, African-American women were significantly more likely to choose an IUD,
      while Hispanic women were significantly more likely to choose subdermal implants
      (p=0.002). Conclusion: Different populations choose subdermal implants versus
      IUDs for contraception. Further research is needed to determine etiologies for
      these differences.

PMID- 30226693
TI  - [Study on the Crystal Structure of Cellulose in Bamboo with Synchrotron Radiation
      Wide Angle X-Ray Scattering].
AB  - The crystal structure of cellulose will directly affect the properties of bamboo
      fiber -reinforced composite, but the unit cell of native cellulose in bamboo has
      never been investigated. The most accepted model for the structure of native
      cellulose is Meyer-Misch model which provides a reference to understand the unit
      cell of native cellulose in bamboo. The native cellulose consists of two
      different crystal structures (I(alpha) and I(beta)) which exist in different
      plants with different proportions. Because of this situation, the crystal
      structure of bamboo cellulose should have a unique model. The moso bamboo
      (Phyllostachys edulis (Carr. ) H. de Lehaie)was selected. The crystal structure
      of cellulose of bamboo was investigated with two dimensional synchrotron
      radiation wide angle X-ray scattering (SR-WAXS). The values of the interplanar
      spacings of each peak were obtained from SR-WAXS patterns, and then crystal
      structure parameters were calculated according to monoclinic crystal system. The
      results show that the fibre axis of a bamboo cellulose unit cell with a
      monoclinic unit cell of a=8.35 A, b (fiber axis)=10.38 A, c=8.02 A, beta=84.99
      degrees . This model has a two antiparallel arrangement for the chains in unit
      cell, with four glucose residues. Thus, the model may be used to provide a
      theoretical basis for high value-added bamboo fiber -reinforced composite.

PMID- 30226694
TI  - "Pause" for Resident Education in the Operating Room.
AB  - Objective: To determine if asking residents to discuss their specific learning
      objectives with the attending physician prior to beginning a surgical case would
      improve the educational experience in the operating room. Study Design: This was
      a prospective nonrandomized cohort study utilizing a self-administered
      questionnaire. Prior to the intervention, residents and attendings were asked to
      fill out surveys evaluating the educational experience in the operating room.
      Subsequently, attending physicians were instructed to ask residents at the
      beginning of the surgery, "What are your goals for this surgical case?" During
      this intervention period, the same anonymous survey was filled out.
      Preintervention and postintervention answers were compared by t test and Fisher's
      exact test. Results: A total of 49 preintervention and 47 postintervention
      resident-attending survey pairs were collected. After implementation of the
      intervention, 100% of residents reported having surgical goals for the procedure
      as compared to 45% prior to the intervention (p<0.0001). Additionally, during the
      intervention residents reported they were better able to maximize learning
      opportunities and were more satisfied with their participation in the case.
      Attending physicians were more likely to be aware of resident learning objectives
      after the intervention. Conclusion: We propose the routine addition of an
      educational pause to the surgical time out.

PMID- 30226699
TI  - [Effect of Raw Materials and Preparing Process on the Composition of Lime-Ash].
AB  - As the saying goes that "no ash, no glaze", lime-ash has been the core material
      widely used to prepare glaze in ancient China. Among all the lime-ashes, those
      made in Jingdezhen are the most influential and representative ones. Not only did
      lime-ash contribute greatly to the prosperity of porcelain making of Jingdezhen
      in Song, Yuan, Ming and Qing Dynasty, but also it has a complicated, rigorous and
      a touch of "mysterious" in its preparation process, technical principle and glaze
      mechanism. Therefore, the research of the lime-ash has been an important subject
      in exploring the "secret" of ancient Chinese porcelain production by Chinese and
      foreign researchers. In this paper, four representative firewood and two lime
      stones as the raw materials were collected for the comparative studies, and three
      kinds of lime-ash with different smolder times were collected from one of the
      only two traditional lime-ash workshops in Shou'an town nearby Jingdezhen urban
      area. The chemical composition and phase composition of the raw materials and
      lime-ash with different smolder times made in Jingdezhen were discussed by
      testing with the Energy Dispersive X Ray Fluorescence (EDXRF) and X-Ray
      Diffraction (XRD). The results showed that Fe(2)O(3), MnO contents reaches 1.41%
      and 1.52% respectively, but the P(2)O(5) content is just 0.54% of Langqi grass
      which is lower than other firewood that is not only benefited to form the
      characteristic of "Green in the white" in Jingdezhen traditional glaze, but also
      is favor to enhance the transparency of glaze and promote the coloration of
      traditional under-glazed color painted porcelain, such as the blue and white
      porcelain. The CaO content of grey lime stone is lower than that of the black
      lime stone with MgO content of 35.79%.This could be the main reason why the
      craftsmen prefer to use black lime stone to prepare lime-ash. In addition, the
      EDXRF results show that the K(2)O, P(2)O(5), MnO and Fe(2)O(3) contents have
      increased as the time of smoldering increases. In the meanwhile, the calcium
      carbonate (CaCO(3)) phase has also increased, but the calcium hydroxide
      (Ca(OH)(2)) phase has decreased. The study helps Jingdezhen porcelain "look like
      jade" and is also good to avoid the "thickness" of glaze when there is a certain
      amount of Ca(OH)(2) in glaze. So it could be concluded that the unique raw
      materials and smolder technology of the lime-ash which have provided the
      technical support for the development of lime-ash glaze are the unique features
      of ancient Jingdezhen ash glaze.

PMID- 30226700
TI  - Correlation Analysis of the STAT3 Polymorphism and Transcription of Survivin and
      VEGF in Missed Abortion: Experience Among Women of the Chinese Han Population.
AB  - Objective: To investigate the relationship between STAT3 gene polymorphism and
      missed abortion (MA), and the influence of STAT3 gene polymorphism on the
      expression of VEGF and survivin. Study Design: The missed abortion group included
      188 cases of MA. The control group consisted of 200 cases of surgically induced
      abortion in normal pregnancy. All patients were of Han ethnicity from P.R. China.
      STAT3 gene from patients' peripheral blood was detected using fluorescent probe
      real-time quantitative polymerase chain reaction (PCR), which was further
      analyzed to clarify genotype frequency. Survivin and VEGF mRNA levels in
      particular genotypes were also detected using qPCR. Results: The STAT3 rs1053004
      C/C genotype incidence in the MA group was significantly higher than that in the
      control group (p<0.05), while the STAT3 rs1053004 T/T and T/C genotypes showed no
      significant difference between the 2 groups (p>0.05). The STAT3 gene locus
      rs1053023 genotypes of the 2 groups were not significantly different, either
      (p>0.05). Furthermore, survivin and VEGF mRNA levels in the peripheral blood of
      the patients with STAT3 gene loci rs1053004 C/C were significantly decreased as
      compared to the control group (p<0.05). Conclusion: Our study identified the
      STAT3 rs1053004 C/C as a high-risk genotype in MA with lower survivin and VEGF
      transcription levels in the peripheral blood.

PMID- 30226701
TI  - [The Analysis of Element and Measure Analysis of NMR Spectrum and XRD Spectrum
      for High Purity 3,4,9,10 Perylenetetracarboxylic Dianhydride-PTCDA].
AB  - vacuum sublimation method was used to purify the homegrown 3,4,9,10
      perylenetetracarboxylic dianhydride(PTCDA)powder with a purity of 98% in its
      sublimation point of 450 C. With Bill's law and ultraviolet-visible
      spectrophotometer testing analysis, its purity reached to 99.8%. Meanwhile, the
      contents of C and H elements in the pre-and post-purified molecules were also
      measured by using elemental analyzer. The measured results indicate that the
      contents of C and H elements in the post-purified the molecules are very close to
      the theoretical value. H element in the molecular structure was investigated with
      nuclear magnetic resonance (NMR) spectroscopy and the results demonstrated that
      there are an equal number of H atoms in two different chemical environments and
      it can only be located on the aromatic ring. By discussing the chemical bond
      formation of PTCDA molecules, the C, H and O atoms in high purity PTCDA molecules
      are mainly covalent bonds. The crystalline state and crystal structure of this
      organic material were tested and analyzed by X-ray diffractometer. The results
      suggest that the post-purified PTCDA power existed alpha-PTCDA and beta-PTCDA two
      phases, in which alpha-PTCDA phase is major component while beta-PTCDA phase
      accounts for about one five of the total ingredients. Besides, the crystal cell
      belonged to bottom-centered monoclinal structure. Meanwhile, the crystal state,
      grain size and band structure of PTCDA single crystal thin films formed on the
      surface of p-type silicon in its sublimation point are investigated in detail.
      During the high-purity alpha-PTCDA forming organic single thin film on the
      surface of p-type single silicon, the pi-electron cloud covered on the top,
      bottom and two sides of its thin film's molecular layer plane. Due to the
      formation of delocalized bond that attributed to the overlap of the outermost
      valence electron orbital of C, H, O atom, the valence electrons generate co
      movement and the energy level splitting for the band. The energy difference
      between valence band and the first tight binding is 2.2 eV which lead to this
      organic material possessing the properties of semiconductor conduction. In
      addition, this organic material with the intrinsic carrier concentration for 1014
      cm-3 belong to weak p-type organic semiconductor material. This organic material
      combines with the surface of p-type silicon to form hetehomo-type heterojunction
      which is provided with excellent response for visible light to near infrared
      wavelengths of light.

PMID- 30226702
TI  - Management of Nephrotic Syndrome in the Pregnant Patient.
AB  - Objective: To present a case series of pregnant women with nephrotic syndrome,
      describe maternal and fetal outcomes, and propose treatment strategies. Study
      Design: A retrospective cohort case review of 11 pregnant women with nephrotic
      syndrome was performed over 2 years. Treatment regimens and trends were recorded.
      Linear regression was used for continuous outcomes, and logistic regression for
      categorical outcomes (p<0.05). Results: On first admission, 3 of 11 patients had
      a serum creatinine >1.4 mg/dL; all 11 exhibited an antepartum increase in
      creatinine. Two required antepartum dialysis, and 3 were dialyzed postpartum.
      Initial mean 24-hour urine protein was 10,522 mg (2,160-36,603) and increased to
      26,220 mg (4,650-49,980). Pregravid weight increased from a mean 95 kg (BMI 33.8)
      to 112 kg (BMI 39.9) at time of delivery. Mean antepartum and postpartum diuresis
      was 33.2 L (+/-25.8) and 5.2 L (+/-8.2), respectively. Mean serum albumin levels
      were 2 g/dL. Ten patients received intravenous diuretics and 9 received
      intravenous albumin. Mean gestational age at delivery was 34w 3d (30.4-38.4).
      Conclusion: Pregnant women with nephrotic syndrome can be managed successfully by
      a collaborative team of obstetricians and nephrologists with careful diuresis,
      repletion of albumin, and administration of anticoagulants, when necessary, to
      deliver a healthy, probably preterm, neonate.

PMID- 30226703
TI  - [A Research on Filed-of-View (FOV) Widening and Thermal-Phase-Drift (TPD)
      Compensating Technology Applied in a Polarized Interference Imaging Spectrometer
      (PIIS)].
AB  - The Polarized Interference Imaging Spectrometer (PIIS), which is based on the
      theory of Fourier Transform Spectroscopy, is consisted of a series of
      birefringent crystals such as polarizers, a beam splitter as well as various
      lengths of birefringent crystals required to achieve large delays. The PIIS,
      compared with a traditional grating-based dispersion spectrometer, has various
      advantages of multiple-channel measurements, simultaneous information acquisition
      of both original images and fringes containing spectral details, large light
      flux, better light signal-to-noise ratio (SNR) as well as anti-vibration etc.
      Therefore, the PIIS has also been developed in a range of astronomy and
      astrophysics areas such as remote sensing, extrasolar planet radial velocity
      measurements, spacecraft design, lunar exploration etc. However, by reviewing of
      former works and references, two major drawbacks still remain in PIIS and need to
      be fixed. For one thing, the classic PIIS has a very limited field-of-view (FOV)
      around +/-2 degrees , which means the acquired fringes on the image plane will
      show quite strong non-linear distortion and hence degrade the accuracy of
      spectral reconstruction via Fourier transform. For another, the random thermal
      phase-drift (TPD), given rise from both thermal expansion and birefringence
      variation caused by the environmental temperature fluctuation, has barely been
      studied before and will inevitably result in extra radial velocity error based on
      Doppler Spectroscopy. In this paper, a noble polarization interference imaging
      spectrometer with the emphasis on the FOV widening technology is introduced. This
      technology, using a compensated Savart plate containing a half-wave plate
      sandwiched between two orthogonally placed displacer plates as a compensated
      Savart plate, produces an angle-dependent phase shear to create parallel spatial
      interference fringes with a FOV around +/-10 degrees . This improvement not only
      enhances the accuracy of Fourier Transform algorithm but also increases input
      luminous flux and therefore even weak input spectrum detection and calibration
      results with high SNR can be fully accomplished. Also, a secondary set of
      birefringent plates (alpha-BBO and LiNbO3) with opposite thermal properties is
      proposed to passively diminish TPD caused by temperature fluctuation. The
      experiment shows that thermal-drift-phase error is perfectly restricted within
      0.02 rad in the laboratory environment. As a consequence, this advanced PIIS is
      eligible to realize the fast and accurate measurement and calibration application
      in the field of large astronomical spectral instruments with ultra-high spectral
      resolution occasions such as Astronomical Frequency Comb.

PMID- 30226704
TI  - [Refractive Index Insensitive Temperature Sensor Based on Cascading Single Mode
      Fiber with Few Mode Fiber].
AB  - A refractive index insensitive temperature sensor is proposed base on cascading
      single mode fiber with few mode fiber(FMF). During the sensor preparation, the
      splicing current is set to 100 mA, and a section of FMF is no core-offset
      splicing between two single-mode fibers. Therefore, it can motivate the
      transmission mode preferably and form optical fiber Mach-Zehnder interferometer.
      The mode phase difference in FMF will be changed according to the outside
      environment. It will cause interference fringe shift. The parameter to be
      measured can be achieved by detecting the amount shift of interference spectrum.
      The FMF can transmit four modes with LP01, LP11, LP21, LP02. The transmission
      spectrum is also analyzed, which shows that they have two modes of LP01 and LP11
      in sensor with the length of 81.5 mm. In the refractive index and temperature
      sensing experiment, the cascading FMF sensor with the length of 81.5 mm is used.
      The results show that the transmission spectrum of sensor appears obvious blue
      shift as temperature is increasing, the temperature sensitivity can be up to 
      85.9 pm.C-1 within the range of 27.6~93.8 C with good linearity. The refractive
      index sensitivity is 3.697 34 nm.RIU-1 within the range of 1.347 1~1.443 9. There
      is no obvious shift phenomenon in the transmission spectrum with the feature of
      refractive index insensitive. Therefore, compared with the traditional cladding
      mode and multimode interferometric fiber-optic sensor, the proposed sensor based
      on FMF is easier to control and analyze transmission mode has the advantages of
      simple structure, easy process and high sensitivity. It can avoid cross
      sensitivity between temperature and refractive index measurement. Thus, it can be
      used for temperature detection of power system, biomedicine, aerospace and other
      fields.

PMID- 30226705
TI  - Influence of Residency Training on Operative Vaginal Delivery in Independent
      Practice.
AB  - Objective: To determine if residency training in the use of forceps and vacuums
      in vaginal deliveries is associated with their use in postgraduate practice.
      Study Design: We surveyed all Ob/Gyn residency graduates of 4 academic programs
      from 2004-2012. The average number of vacuums and forceps performed per
      graduating resident was linked to respondents, who were then grouped by self
      report as using forceps alone, vacuums alone, or both in practice. Multivariable
      logistic regression determined predictors of use of forceps and vacuums in
      practice Results: The response rate was 61.2% (n=200). Those practicing
      obstetrics (n=171) were classified as forceps only (24%), vacuums only (22%), or
      both (54%). Use of forceps in practice was greater for those who graduated within
      the last 5 years (OR 7.55, 95% CI 2.37-24.07), felt inadequately trained in
      vacuums (OR 4.58, 95% CI 1.23-17.00), cared for a patient population <50%
      privately insured (OR 4.08, 95% CI 1.58-10.52), and performed more forceps in
      residency (OR 1.69, 95% CI 1.31-2.18 per 5 forceps performed on average). The
      only significant predictor of vacuum use was the number of vacuum deliveries
      performed in residency (OR 3.71, 95% CI 2.28-6.01 per 5 vacuums performed on
      average). Conclusion: Independent practice pattern for operative vaginal delivery
      reflects residency training for both vacuums and forceps.

PMID- 30226706
TI  - [Combined Transmission Laser Spectrum of Core-Offset Fiber and BP Neural Network
      for Temperature Sensing Research].
AB  - When studying the wavelength response to the temperature of the single mode fiber
      interference laser spectrum, a three layer BP neural network model is built to
      solve the problem of high complexity and low accuracy of temperature measurement
      system. With the Discussion of the parameters of network model, we obtain the
      optimal network structure by comparing the data acquisition which is the laser
      wavelength corresponding to its temperature trained by BP neural network. With
      network training completed and the wavelength of input laser reached the
      specified value, the corresponding temperature prediction can be obtained from
      the output layer. In conclusion, it shows a clear correlation between the
      predictive value and the actual value, i.e. the former is approximately equal to
      the latter. The correlation coefficients of the calibration and prediction are
      0.999 61 and 0.979 27, respectively; while the standard errors of the calibration
      and prediction are 0.017 5 and 0.144 0, respectively, and the average relative
      error of prediction set is 0.17%. The residual predictive deviation (RPD),
      obtained theoretically, is 5.258 3. RPD>3. It indicates that the calibration
      effect is good, and the model can be used for practical testing. In addition, the
      algorithm is also applied to the system of double coupled structure with single
      mode core-offset fiber and correction for the temperature measurement. The
      results show that BP neural network method can deal with the nonlinear
      relationship between the laser spectral data and the temperature in the optical
      fiber temperature measurement system. The correlation and the average relative
      error between the predicted temperature and the true temperature are 0.996 58 and
      0.63%, respectively. The precision and stability of the fiber optic temperature
      sensor are significantly improved. At the same time, the feasibility of the
      proposed algorithm is verified in the fiber optical sensor system. It also
      provides a new way for the accurate measurement of pressure, curvature and other
      physical quantities of the core-offset fiber.

PMID- 30226707
TI  - The Intramolecular Spin-Spin Interactions in Ruthenium Complexes of Pyrazole
      Derivatives.
AB  - The spin-spin coupling can provide useful information for analysing the structure
      of a system and the extent of non-covalent bonds interactions. In this study, we
      present the isotropic NMR properties and spin-spin coupling involving ruthenium
      ligand (Ru-L) bonds and other spin-spin interactions obtained from DFT
      calculations. The proton shift which in close proximity with the Ru and Cl (or O)
      atoms are characterised with lower and higher chemical shift respectively. Though
      Ru-Cl bond has longer bond length than all other Ru-L bonds, yet its spin-spin
      coupling is higher than others because of a very high contribution of PSO which
      is far higher than the contribution from FC terms. In all other Ru-L bonds, FC is
      the most significant Ramsey terms that define their spin-spin coupling. Both the
      isotropic and anisotropic shielding of the Hz of the pyrazole is lower than Hc of
      the cymene and the spin-spin coupling 3J(Hz...Hz) of the pyrazole are less than
      half of the 3J(Hc...Hc) of the cymene unit in the complexes. There is a little
      increase in both the 3J(Hc...Hc) and 3J(Hz...Hz) spin-spin coupling in the
      hydrolysed complexes compare to the non-hydrolysed complexes. The isotropic and
      anisotropic shielding tensor of Ru atoms increases in magnitude as the complexes
      get hydrolysed that could be ascribed to a more deshielding chemical
      environments.

PMID- 30226708
TI  - Distinguishing the Rare Spectra with the Unbalanced Classification Method Based
      on Mutual Information.
AB  - Distinguishing the rare spectra from the majority of stellar spectra is one of
      quite important issues in astronomy. As the size of the rare spectra is much
      smaller than the majority of the spectra, many traditional classifiers can't work
      effectively because they only focus on the classification accuracy and have not
      paid enough attentions on the rare spectra. In view of this, the relationship
      between the decision tree and mutual information is discussed on the basis of
      summarizing the traditional classifiers, and the cost-free decision tree based on
      mutual information is proposed in this paper to improve the performance of
      distinguishing the rare spectra. In the experiment, we investigate the
      performance of the proposed method on the K-type, F-type, G-type, M-type datasets
      from Sloan Digital Sky Survey (SDSS), Data Release 8. It can be concluded that
      the proposed method can complete the rare spectra distinguishing task compared
      with several traditional classifiers.

PMID- 30226709
TI  - Impacts of Related Risk Factors on the Efficacy of Interventional Treatment
      Towards Intractable Postpartum Hemorrhage.
AB  - Objective: To investigate the risk factors that impact the efficacy of
      interventional treatment of intractable postpartum hemorrhage (IPH). Study
      Design: A total of 64 IPH patients were admitted and received interventional
      treatment at First Hospital of Shanxi Medical University from January 2012 to
      September 2014, among whom 57 cases were successfully treated (bleeding stopped),
      while 7 cases failed. The clinical data of the success group and the failure
      group were observed for the multivariate analysis of the possible reasons that
      might cause hemostatic failure. Results: The univariate analysis of each
      suspected factor of hemostatic failure showed that history of uterine scar,
      combined use of uterotonics, uterine inertia, and placenta exhibited
      statistically significant differences between the 2 groups (p<0.05); the
      multivariate logistic regression analysis showed that history of uterine scar and
      combined use of uterotonics were the risk factors for the interventional
      treatment failure of IPH, with OR values of 11.23 (95% CI 1.26~100.22) and 12.83
      (95% CI 1.05-156.34), respectively. Conclusion: History of uterine scar and
      combined use of uterotonics were the risk factors for interventional treatment
      failure of IPH.

PMID- 30226710
TI  - The Application of THz Spectroscopy and GA-BP in Methanol Concentration
      Detection.
AB  - At ambient temperature and atmospheric pressure, making use of a photoconductive
      antenna terahertz time-domain spectrograph and a self-designed air chamber, the
      terahertz time-domain spectroscopy (THz-TDS) technique test of methanol gas in
      the range of 0.1~3.0 THz shows that the methanol gas has no obvious absorption
      peaks in the range of 0.1~3.0 THz and has obvious absorption peaks in the range
      of 0.1~1.0 THz. In order to improve the determination accuracy of the
      concentration of the methanol gas, the author detected 15 groups of methanol gas
      with different concentrations on the basis of the relationship between the
      strengths of 15 characteristic absorption peaks of different locations and the
      concentration of the methanol gas, and obtained the difference curve of the of
      the characteristic absorption peaks. Based on the function approximation of BP
      neural network, the author optimized the initial weights and biases of the BP
      neural network by using the GA the genetic algorithm, which has higher rate of
      convergence to prevent from getting into local optimum easily, and constructed
      the mathematical model with the purpose of predicting the methanol gas
      concentration. The test results show that the neural network is applicable to
      predict methanol gas in the volume concentration range of 0.028 3~0.424 6 m3.L(
      1), the average relative standard deviation of the 2 sets of samples is 1.7%, the
      average recovery rate is 98%, the error precision of the neural network is 10(
      1), and correlation coefficient of the measured values and the predicted values
      is 0.996 77. The test basically achieved ideal predicted results. The research
      results obtained experimental data of methanol gas in the terahertz frequency
      band and found that the method of combining terahertz time-domain spectroscopy
      with GA-BP neural network can effectively detect the volume concentration of
      methanol gas, and provided a new method for the detection of concentration of
      methanol gas.

PMID- 30226711
TI  - Clinical Risk Factors Do Not Predict Shoulder Dystocia.
AB  - Objective: To compare 2 different risk factor models for the prediction of
      shoulder dystocia. Study Design: We performed a retrospective study of women with
      vaginal deliveries at a single institution over an 8-year period. Two distinct
      multivariable logistic regression models were used to evaluate the occurrence of
      shoulder dystocia: a traditional model used information based on birthweight and
      macrosomia, and a clinical model used information based on esti-mated fetal
      weight and suspected macrosomia. Results: Of the 13,998 deliveries analyzed,
      there were 221 cases of shoulder dystocia (1.6%). In addition to the macrosomia
      or suspected macrosomia variables, the final models included prolonged second
      stage of labor, diabetes status, and oxytocin use. Neither model was highly
      sensitive or highly specific, and neither demonstrated a cutoff threshold that
      yielded a clinically viable PPV. Conclusion: Despite the presence of 1 or more
      risk factors for shoulder dystocia, its occurrence remains largely an
      unpredictable clinical event.

PMID- 30226712
TI  - Research on the Preparation and Chromaticity Coordinates Shift Mechanism of
      Organic White Light Top-Emitting Devices.
AB  - The top emission organic light-emitting devices were fabricated on the multi
      layers metal anode with co-doping method in single host system. In experiment,
      the multilayer Al/Mo/MoO(3) anode on silicon are deposited, systematically
      analyzed the effect MoO(3) thickness on the reflectance and found the mechanism
      of the MoO(3) thickness variation to the reflectivity of Al/Mo/MoO(3) on silicon.
      Experimental results showed that the luminous intensity of blue, green and red
      appear to change according to the current density increase, and compared with the
      red intensity, the luminous intensity of blue and green gradually increased. The
      emission in this host-guest co-doping system is considered to usually involve two
      emission mechanisms, energy transfer and carrier trapping, and the energy
      transfer and carrier trapping between the host-guest should be responsible for
      chromaticity coordinates shift of organic white emitting light devices. In
      addition, through further study, it is proved the electroluminescence intensity
      of dopant linearly decrease with the driving voltage applied to the device by
      theoretical and experimental results.

PMID- 30226713
TI  - Identification of Plant-Pathogenic Fungi Using Fourier Transform Infrared
      Spectroscopy Combined with Chemometric Analyses.
AB  - Identification of plant-pathogenic fungi is time-consuming due to cultivation and
      microscopic examination and can be influenced by the interpretation of the micro
      morphological characters observed. The present investigation aimed to create a
      simple but sophisticated method for the identification of plant-pathogenic fungi
      by Fourier transform infrared (FTIR) spectroscopy. In this study, FTIR-attenuated
      total reflectance (ATR) spectroscopy was used in combination with chemometric
      analysis for identification of important pathogenic fungi of horticultural
      plants. Mixtures of mycelia and spores from 27 fungal strains belonging to nine
      different families were collected from liquid PD or solid PDA media cultures and
      subjected to FTIR-ATR spectroscopy measurements. The FTIR-ATR spectra ranging
      from 4 000 to 400 cm-1 were obtained. To classify the FTIR-ATR spectra, cluster
      analysis was compared with canonical vitiate analysis (CVA) in the spectral
      regions of 3 050~2 800 and 1 800~900 cm-1. Results showed that the identification
      accuracies achieved 97.53% and 99.18% for the cluster analysis and CVA analysis,
      respectively, demonstrating the high potential of this technique for fungal
      strain identification.

PMID- 30226714
TI  - Lifetime major depression and grey-matter volume
AB  - Background: There is evidence of structural brain alterations in major depressive
      disorder (MDD), but little is known about how these alterations might be affected
      by age at onset or genetic vulnerability. This study examines whether lifetime
      episodes of MDD are associated with specific alterations in grey-matter volume,
      and whether those alterations vary according to sex or serotonin transporter
      linked promoter region (5-HTTLPR) genotype (LL, SL or SS). Methods: We used
      structural MRI to acquire anatomic scans from 610 community-dwelling
      participants. We derived quantitative regional estimates of grey-matter volume in
      16 subregions using FreeSurfer software. We diagnosed MDD according to DSM-IV
      criteria. We adjusted analyses for age, sex, total brain volume, education level,
      head injury and comorbidities. Results: Lifetime MDD was associated with a
      smaller insula, thalamus, ventral diencephalon, pallidum and nucleus accumbens
      and with a larger pericalcarine region in both men and women. These associations
      remained after adjustment for false discovery rate. Lifetime MDD was also
      associated with a smaller caudate nucleus and amygdala in men and with a larger
      rostral anterior cingulate cortex in women. Late-onset first episodes of MDD
      (after age 50 years) were associated with a larger rostral anterior cingulate
      cortex and lingual and pericalcarine regions; early-onset MDD was associated with
      a smaller ventral diencephalon and nucleus accumbens. Some associations differed
      according to 5-HTTLPR genotype: the thalamus was smaller in participants with MDD
      and the LL genotype; pericalcarine and lingual volumes were higher in those with
      the SL genotype. Conclusion: Major depressive disorder was associated with
      persistent volume reductions in the deep nuclei and insula and with enlargements
      in visual cortex subregions; alterations varied according to age of onset and
      genotype.

PMID- 30226715
TI  - Analysis of Thermal Field Distribution in Winter over Beijing from 1985 to 2015
      Using Landsat Thermal Data.
AB  - Heat supply, automobile exhaust, industrial production and decrease of thermal
      inertia in winter caused by the decrease of vegetation coverage leads to an
      obvious difference in the distribution of the land thermal field in the winter
      compared with other seasons. The Urban thermal field distribution in the winter
      directly affects the spread of air pollutants, which has important implications
      for analyzing the contribution of the thermal field to particulate air pollution.
      Atmospheric transmissivity and atmospheric upwelling/downwelling radiance in
      simulations are first calculated using the moderate spectral resolution
      atmospheric transmittance algorithm and computer model (MODTRAN). Then, we solve
      the radiative transfer model of the thermal infrared band by constructing a look
      up table. In addition, the accuracy estimation is performed using the simulated
      data, showing that when the error range of emissivity and water vapor content are
      confined to +/-0.005 and +/-0.6, respectively, the temperature retrieval error
      are less than 0.348 and 2.117 K, respectively indicating the high retrieval
      accuracy of the method. In addition, the long-term sequenced Landsat TM and ETM+
      data were selected to retrieve land surface temperature (LST) during 1985-2015.
      The analysis of the temporal and spatial distribution of thermal fields in
      Beijing show that the spatial and temporal variations are observable. The spatial
      variation covers four levels: high temperature is distributed within the second
      ring, low temperature loops are distributed between the second and the fifth
      ring, high temperature is distributed in the outer suburb areas and the lowest
      temperature is distributed in the western mountainous areas. Meanwhile, the
      temporal variation of thermal field distribution changed a great deal during the
      rapid development in the past 3 decades: the low temperature loop expanded from
      the third to the sixth ring; the intensity and scope of the heat island effect
      within the second ring increased gradually.

PMID- 30226716
TI  - Trace Element Analysis by PIYE and ICP-AES of Raw Material and Ancient Serpentine
      Artifacts from China.
AB  - This work mainly talks about serpentine mineral with the aim to explore the
      possible raw materials sources of ancient serpentine artifacts by trace element
      content analysis. The major and trace elements of serpentine samples from several
      typical deposits in China were nondestructively determined by external-beam
      proton-induced X-ray emission (PIXE). For comparison, trace element
      concentrations were destructively measured by inductively coupled plasma-atomic
      emission spectroscopy (ICP-AES). The results showed the trend of the trace
      element contents of serpentine jade obtained by the two methods have preferably
      coherence, which indicate that the nondestructive technique of PIXE can be
      applied to trace element analysis of serpentine. The relationship between trace
      element contents and serpentine formation mechanism was discussed. The difference
      of the trace elements contents in these serpentine minerals is obvious. It can be
      used to distinguish the different kinds of serpentine formed by different
      mechanisms. A low amount of Ni and almost no Cr and Co were found in type I
      serpentine group mineral, whereas significant amounts of Cr, Co and Ni were found
      in Type II serpentine group mineral. The chemical composition of 18 ancient
      serpentine artifacts were analyzed by PIXE, they were unearthed from 14 sites and
      tombs in provinces of Zhejing, Jiangsu, Henan, Anhui and Hubei and dated from
      Neolithic Age to the Warring States Period (4585 BC-231 BC). By comparing the
      trace element contents between ancient serpentine artifacts and two kinds of
      serpentine samples, the provenance of ancient serpentine artifacts were
      preliminarily inferred. It is beneficial to try to explore the possible raw
      material of ancient serpentine artifacts based on the relationship between the
      trace element contents and serpentine formation mechanism in this article.

PMID- 30226717
TI  - Azoospermia Type Does Not Affect Intracytoplasmic Sperm Injection Results When
      Microdissection Testicular Sperm Extraction Is Performed.
AB  - Objective: To investigate the effect of azoospermia type on fertilization and
      clinical pregnancy rates when microdissection testicular sperm extraction (TESE)
      is performed for sperm retrieval in nonobstructive azoospermia (NOA). Study
      Design: STUDY DESIGN: Patients who underwent microdissection TESE for NOA and
      conventional TESE for obstructive azoospermia (OA) were included in the study.
      Intracytoplasmic sperm injection (ICSI) results were compared between groups.
      Results: The mean ages in the 2 groups were similar. FSH and LH levels in the NOA
      group were significantly higher than those of the OA group. Between groups there
      was no statistically significant difference in testosterone levels. The sperm
      retrieval rate was 58.56% in NOA. Fertilization and clinical pregnancy rates were
      similar for patients with NOA and OA. Conclusion: In patients with NOA,
      microdissection TESE accurately determines active spermatogenesis areas via the
      high identification power of the operative microscope. From these areas surgeons
      can collect healthier spermatozoa, which can result in better ICSI outcomes, the
      results of which are similar to those with OA.

PMID- 30226718
TI  - Spectroscopic and Molecular Docking Study on Specific Binding and Inhibition of
      Isoniazid to Human Serum Albumin and Catalase.
AB  - Isonicotinic acid hydrazide (Isoniazid, INH) is one of the most commonly used
      first-line anti-tuberculosis drugs, which has been reported that the high
      concentration of INH in human body can lead to epilepsy, liver function failure,
      and even death. Therefore, studying the potential binding effects of INH on the
      structure and activity of human serum albumin (HSA) and catalase (CAT) is very
      essential for evaluating its toxicity and side effect. In this paper, multi
      spectroscopic and molecular docking methods were used to elucidate the patterns
      of INH to HSA and CAT under imitated physiological conditions. The inner filter
      effect of all fluorescence data in the paper was eliminated to get accurate
      binding parameters. The Stern-Volmer quenching constants (KSV) of both HSA-INH
      system and CAT-INH system inversely correlated with temperatures, demonstrating
      that INH quench the intrinsic fluorescence of HSA and CAT via static quenching.
      The conformational investigation of HSA and CAT through UV-visible absorption
      spectroscopy, synchronous fluorescence and circular dichroism (CD) showed that
      INH could change the micro-environment of tryptophan residues and reduced the
      alpha-helix content of protein. These results demonstrated that the binding of
      INH may lead to the loosening of protein skeleton, which which may affect its
      physiological function. The results of molecular docking revealed that the INH
      was located in Sudlow's site I of HSA. And INH bound to CAT at a cavity among the
      wrapping domain helical domain and beta-barrel, which resulted in the inhibition
      of CAT activity. In addition, Levofloxacin (LVFX) is a new effective and safe
      second-line anti-tuberculosis drugs and can improve the curative effect on anti
      TB by using with other anti-TB drugs, the result of Hill's coefficients (nH)
      about synergy between INH and proved that LVFX promoted the interaction of HSA
      with INH. Moreover, according to the CD spectra, synergy between INH and LVFX
      changed the conformation of HSA and the amount of alpha-helix decreased about
      7.9%. This work will provide important insights into the binding and toxicity
      mechanism of INH to HSA and CAT in vivo and is expected to be helpful in
      evaluating the essential information for using the INH safely.

PMID- 30226719
TI  - Structural Effect on Absorption and Emission Properties of 1,8-Naphthalimide
      Derivatives: a DFT Study.
AB  - Using B3LYP/6-31G(d) model, time depended(TD)-B3LYP/6-31+G(d) method and
      Conductor-like Polarizable Continuum Model (C-PCM)-TD-B3LYP/6-31+G(d) method, we
      calculated the structure and the absorption and emission spectra of a series of N
      substituted 1,8-naphthalimides in both gas-phase and dichloromethane. The
      influence of the substituents on the electronic absorption spectra and their
      emission spectra has been discussed on their calculated frontier molecular
      orbitals contour and their energy levels. Results show that their rings extension
      from CN group and the substituents on their naphthalimic ring play an important
      role in the absorption spectra and the emission spectra properties. Modification
      of OCNCO group and the substituents in their naphthalimic rings breaks the
      structural symmetry. The Mulliken atomic charges values of NO2 groups from S0 to
      S1 in 4 positions are a little greater than the 5-positions, which also mean that
      the 5 position provide more electrons. For MACs of N(Ph)2 and N(Me)2, the 4
      position substituents provide more charges than that of 5 position. They not only
      lead to bigger dipole moments, but also extend frontier orbital contour. Frontier
      orbitals also show that the modification of OCNCN and the introduction N(Me)2,
      N(Ph)2 and NO2 groups extends their pi-pi* excitation scope and decreases their
      energy gap accordingly. Besides, those kinds of molecular design enhance intra
      molecular charge transfer between substituent and naphthalimic ring. Therefore,
      redshift are shown in their absorption and emission spectra, which is also
      verified by calculated results. Their absorption and emission spectra in solvent
      redshift compared with their gas spectra. For the NO2 derivatives, the charge
      transfer state is in the 5 position substituent compounds. For donor
      substituents, charge transfer state lies in their 4 position compounds. When the
      CO group is in the same side with the NO2 group, and the N(Me)2 and the N(Ph)2
      are in the different side with the CO group, compounds have better conduction
      properties. From compound 1 to compound 4, the redshift of the absorption spectra
      in dichloromethane is about 139 nm. The more intramolecular charge transfer, the
      bigger absorption maximum those compounds shown. Above result is in good
      agreement with the 5-position NO2 derivatives and the 4-position N(Me)2, N(Ph)2
      derivatives. Above OCNCO structural change and their charge transfer mechanism
      provide design basis for further 1,8-naphthalmic derivatives.

PMID- 30226720
TI  - Fetal Heart Monitor Tracing in a Pregnancy Complicated by a Ruptured Fetal Vessel
      on the Placenta: A Case Report.
AB  - Background: This report describes the fetal heart rate (FHR) tracing in a
      pregnancy complicated by antenatal spontaneous rupture of fetal vessels on the
      placental surface that resulted in a live birth. Case: 36-year-old woman,
      G2P1001, was being followed with weekly antenatal testing for gestational
      diabetes type A2 on insulin with possible intrauterine growth restriction. She
      presented for an office visit at 37.5 weeks' gestation with a complaint of
      decreased fetal movement. The FHR pattern demonstrated minimal baseline
      variability with an occasional spontaneous deceleration not associated with a
      contraction, an absence of recurrent decelerations, and no accelerations. The
      antenatal evaluation is discussed, and portions of the FHR tracing and the
      placental findings at delivery are provided. Conclusion: The FHR pattern did not
      fit with what is usually depicted with uteroplacental insufficiency or umbilical
      cord entrapment. In addition, even though the fetus is anemic, the process may
      occur too quickly for a sinusoidal pattern to develop.

PMID- 30226721
TI  - Research on Assessment Methods of Spectral Reflectance Data Quality for Computer
      Color Matching.
AB  - Spectral reflectance data quality is important for computer color matching. There
      are two existing methods for evaluating the quality-spectral reflectance method
      and K/S method, which are too complex to apply. In this paper, 45 degrees /0
      degrees  and d/8 degrees  geometric conditions are used in the measurement of
      spectral reflectance of the offset ink samples printed on coated paper and silver
      foiled paper while improvement on the geometric condition is made on the basis of
      the spectral reflectance method. Moreover, a new evaluation method-lightness and
      chromaticity comparative method is put forward, and comparison is made among the
      three methods. The results show that both 45 degrees /0 degrees  and d/8 degrees 
      are feasible in the measurement of spectral reflectance of coated paper; however
      the former one cannot meet the requirement of spectral reflectance measurement of
      silver-foiled paper. In addition, as to d/8 degrees  Specular Component Included
      (SCI), when the silver-foiled paper is taken as the substrate, the reflectance of
      transparent white ink samples are smaller than that of other primary inks; and
      abnormal intersections appear in the curves of cyan and magenta ink respectively
      at the concentration of 60%, resulting in a poor spectra quality at high ink
      concentration; In the figure of lightness and chromaticity curves, there is
      significant divergence of the cyan and magenta ink curves from the referenced
      coated paper. In conclusion, the spectral reflectance of the transparent ink
      should be greater than or at least equal to other primary inks, and the maximum
      concentration of cyan and magenta should be limited; when the coated paper with
      good diffusion performance is taken as the reference, the comparative analysis is
      more intuitive than the two existing methods.

PMID- 30226722
TI  - Pemphigus Vulgaris Presenting as Chronic Vulvovaginal Erosions: The Importance of
      Autoantibody Testing: A Case Report.
AB  - Background: Pemphigus vulgaris is a rare autoimmune bullous disease characterized
      by mucosal erosions. Pathogenic autoantibodies are directed against desmoglein 3,
      leading to intraepidermal blister formation. The oral cavity is typically the
      initial and most common site of involvement, but the female genital tract can
      also be involved. We present a case of pemphigus vulgaris presenting as chronic
      vulvovaginal erosions. Case: A 59-year-old woman presented with a rare sore in
      her mouth and an 18-month history of vaginal burning, irritation, and white
      discharge. Previous workup included negative vaginal culture for yeast,
      nondiagnostic vulvar biopsy, and normal cervical smear. Clobetasol cream had
      provided minimal relief. Biopsy of an erosion of the vulvar vestibule showing
      loss of epidermis with acantholysis prompted indirect immunofluorescence testing.
      High titer immunoglobulin G antibodies directed against epithelial cell surfaces
      confirmed a diagnosis of pemphigus vulgaris, explaining an 18-month history of
      isolated chronic vulvovaginal erosions. Conclusion: Female genital tract
      involvement by pemphigus vulgaris usually occurs in the setting of extensive
      involvement at other sites, most notably the oral mucosa. Primary involvement of
      the genital mucosa is unusual. Confirmatory diagnosis is made with testing for
      autoantibodies, either with direct or indirect immunofluorescence or enzyme
      linked immunosorbent assay.

PMID- 30226723
TI  - Commentary - Broadening our understanding of Canada's epidemics of pharmaceutical
      and contaminated street drug opioid-related overdoses.

PMID- 30226724
TI  - At-a-glance - Opioid surveillance: monitoring and responding to the evolving
      crisis.
AB  - The incidence of opioid-related overdoses is increasing at an alarming pace,
      largely driven by the increased use of fentanyl and its analogues. The need for
      sound and reliable sources of data on opioid use is crucial in order to make
      decisions on implementing efficient interventions, and develop appropriate
      policies and guidelines to mitigate the burden of opioid use. This article
      highlights initiatives undertaken by federal partners to address the opioid
      crisis in Canada. The need for novel surveillance approaches that improve the
      collection and harmonization of drug-related data is also discussed.

PMID- 30226725
TI  - Sentinel surveillance of suspected opioid-related poisonings and injuries: trends
      and context derived from the electronic Canadian Hospitals Injury Reporting and
      Prevention Program, March 2011 to June 2017.
AB  - INTRODUCTION: The opioid epidemic is currently a major public health problem in
      Canada. As such, knowledge of upstream risk factors associated with opioid use is
      needed to inform injury prevention, health promotion and harm reduction efforts.
      METHODS: We analyzed data extracted from 11 pediatric and 6 general hospital
      emergency departments (EDs) as part of the electronic Canadian Hospitals Injury
      Reporting and Prevention Program (eCHIRPP) from March 2011 to June 2017. We
      identified suspected opioid-related injuries using search strings and manually
      verified them. We computed age-adjusted and sex-stratified proportionate injury
      ratios (PIRs) and 95% confidence intervals (CIs) to compare opioid-related
      injuries to all injuries in eCHIRPP. Negative binomial regression was used to
      determine trends over time. We conducted qualitative analyses of narratives to
      identify common themes across life stages. RESULTS: Between March 2011 and June
      2017, 583 suspected opioid-related poisoning/ injury cases were identified from
      eCHIRPP. Most of the cases were females (55%). Many of the injuries occurred in
      patients' own homes (51%). Forty-five percent of the injuries were intentional
      self-harm. Among children (aged 1-9 years), most injuries were caused by
      inadvertent consumption of opioids left unattended. Among youth (aged 10-19
      years) and adults (aged 20-49 years), opioid use was associated with underlying
      mental illness. Overall, the average annual percent change (AAPC) in the rate of
      injuries (per 100 000 eCHIRPP cases) has been increasing since 2012 (AAPC =
      11.9%, p < .05). The increase is particularly evident for males (AAPC = 16.3%, p
      < .05). Compared to other injuries, people with suspected opioid-related injuries
      were more likely to be admitted to hospital (PIR = 5.3, 95% CI: 4.6-6.2).
      CONCLUSION: The upstream determinants of opioid-related injuries are complex and
      likely vary by subpopulations. Therefore, continued monitoring of risk factors is
      important in providing the evidence necessary to prevent future overdoses and
      deaths.

PMID- 30226726
TI  - Patterns of health care utilization among people who overdosed from illegal
      drugs: a descriptive analysis using the BC Provincial Overdose Cohort.
AB  - INTRODUCTION: British Columbia (BC) declared a public health emergency in April
      2016 in response to a rapid rise in overdose deaths. Further understanding of
      health care utilization is needed to inform prevention strategies for individuals
      who overdose from illegal drugs. METHODS: The Provincial Overdose Cohort includes
      linked administrative data on health care utilization by individuals who
      experienced an illegal drug overdose event in BC between 1 January 2015 and 30
      November 2016. Overdose cases were identified using data from ambulance services,
      coroners' investigations, poison control centre calls and hospital, emergency
      department and physician administrative records. In total, 10 455 overdose cases
      were identified and compared with 52 275 controls matched on age, sex and area of
      residence for a descriptive analysis of health care utilization. RESULTS: Two
      thirds (66%) of overdose cases were male and about half (49%) were 20-39 years
      old. Over half of the cases (54%) visited the emergency department and about one
      quarter (26%) were admitted to hospital in the year before the overdose event,
      compared with 17% and 9% of controls, respectively. Nevertheless, nearly onefifth
      (19%) of cases were recorded leaving the emergency department without being seen
      or against medical advice. High proportions of both cases (75%) and controls
      (72%) visited community-based physicians. Substance use and mental health-related
      concerns were the most common diagnoses among people who went on to overdose.
      CONCLUSION: People who overdosed frequently accessed the health care system in
      the year before the overdose event. In light of the high rates of health care
      use, there may be opportunities to identify at-risk individuals before they
      overdose and connect them with targeted programs and evidence-based
      interventions. Further work using the BC Provincial Overdose Cohort will focus on
      identifying risk factors for overdose events and death by overdose.

PMID- 30226727
TI  - At-a-glance - Concurrent monitoring of opioid prescribing practices and opioid
      related deaths: the context in Nova Scotia, Canada.
AB  - Timely public health surveillance is required to understand trends in opioid use
      and harms. Here, opioid dispensing data from the Nova Scotia Prescription
      Monitoring Program are presented alongside fatality data from the Nova Scotia
      Medical Examiner Service. Concurrent monitoring of trends in these data sources
      is essential to detect population-level effects (whether intended or unintended)
      of interventions related to opioid prescribing.

PMID- 30226728
TI  - At-a-glance - What can paramedic data tell us about the opioid crisis in Canada?
AB  - The nature of Canada's opioid crisis necessitates additional data sources that
      can provide a more comprehensive picture of the epidemic, in order to provide
      public health officials and decision-makers with a robust evidence base.
      Paramedic data provide a conduit into the community where overdoses occur.
      Prehospital events and circumstances surrounding opioid-related overdoses provide
      unique opportunities to collect evidence that can contribute to prevention, harm
      reduction and health promotion efforts. Using data extracted from the Ottawa
      Paramedic Service (OPS), this proof-of-concept study demonstrated that paramedic
      response data were useful in providing near real-time epidemiological information
      (person, time and place) on the opioid epidemic and in assessing trends and
      opportunities to develop alert triggers. Between January and June 2017, the OPS
      responded to an average of four opioid-related calls each week. On average, 0.5
      mg of naloxone was administered each time. For the study period, linear trends
      show a small but insignificant increase in calls (p = 0.18). A higher volume of
      calls occurred between April 16 and 29, 2017. According to local media reports,
      this spike in paramedic responses was due to the arrival of high-grade fentanyl
      in Ottawa. With further validation, paramedic data can potentially provide a
      novel data source to monitor opioid-related overdoses.

PMID- 30226729
TI  - At-a-glance - The role of opioid toxicity in suicide deaths in Alberta, 2000 to
      2016.
AB  - Given the current opioid crisis in Canada, there is interest in the role of
      opioid toxicity in suicide deaths, particularly in whether any observed patterns
      are similar to those of unintentional deaths. The present analysis examined
      characteristics of opioid-toxicity suicide, and its role in relation to other
      suicide methods, from 2000 to 2016 in Alberta. It does not appear that the opioid
      crisis has resulted in a disproportionately higher number of suicides in Alberta.
      Individuals who die from unintentional opioid toxicity and those who die by
      opioid-toxicity suicide are likely distinct populations, requiring nuanced public
      health responses for prevention.

PMID- 30226730
TI  - Successful Treatment of a Pararenal Pregnancy Using High-Dose Methotrexate
      Regimen: A Case Report.
AB  - Background: Upper abdominal pregnancy is rare. Most patients present with
      hemoperitoneum, requiring emergency laparotomy. Case: A 32-year-old woman
      presented with acute abdominal pain and an elevated beta-human chorionic
      gonadotropin (beta-hCG) level. Ultrasound, computerized tomography (CT) scans,
      and laparoscopy failed to locate the source of elevated hCG. Subsequent positron
      emission tomography (PET)-CT demonstrated a cystic mass in the left pararenal
      region with no increased uptake. Repeated ultrasound scan revealed a live fetus
      implanted laterally to the abdominal aorta. After failing to respond to
      methotrexate at the usual dosage, a regimen used in gestational trophoblastic
      neoplasia was given. The pregnancy underwent miscarriage afterwards, and the hCG
      level gradually returned to normal. Conclusion: The site of an ectopic pregnancy
      should be sought thoroughly to avoid missing an abdominal pregnancy and hence
      disastrous hemoperitoneum. While medical therapy with high-dose methotrexate is
      not a standard treatment, it can be considered after failing the traditional
      therapy, provided that there is adequate treatment monitoring and expertise in
      handling the side effects of the medication.

PMID- 30226731
TI  - Successful Treatment of a Recurrent Cesarean Scar Pregnancy by Transvaginal
      Cesarean Scar Pregnancy Lesion Resection: A Case Report.
AB  - Background: Cesarean scar pregnancy (CSP) is a type of ectopic pregnancy with the
      gestation sac located on a previous cesarean scar. Recurrent CSP (RCSP) is the
      occurrence of 2 or more consecutive CSPs. Until this case, there have been only 8
      previous reported cases of RCSPs in the English-language literature. Case: A 30
      year-old, Chinese woman was admitted to our hospital for RCSP. We had
      successfully terminated her first CSP by a series of treatments including uterine
      arterial embolization with local methotrexate injection, mifepristone, and
      misoprostol administration, as well as an ultrasound-guided suction curettage
      evacuation. However, this time we performed only a transvaginal CSP lesion
      resection, which achieved an improved outcome. Conclusion: This case highlights
      the likelihood of RCSP and the need for transvaginal CSP lesion resection to
      decrease the risk of RCSP in CSP patients who desire future pregnancy.

PMID- 30226732
TI  - Velamentous Umbilical Cord Insertion and Ruptured Fetal Vessel: A Cause of Fetal
      Maternal Hemorrhage: A Case Report.
AB  - Background: Fetal hemorrhage is rare but can result in rapid fetal compromise.
      Abnormally located fetal vessels within the membranes increase the risk for their
      rupture and subsequent hemorrhage. The classic example of this is vasa previa.
      Case: We present a case of acute fetal hemorrhage resulting from a ruptured fetal
      vessel. During induction of labor, significant fetal heart rate deceleration
      occurred, coinciding with acute vaginal bleeding and amniotomy. A depressed, live
      female neonate was delivered by emergency cesarean section. Examination of the
      placenta revealed a velamentous cord insertion and a ruptured fetal vessel
      coursing through the chorioamniotic membranes. Neonatal resuscitation included
      red blood cell transfusion for hypotension and low hematocrit. The neonate made a
      full recovery. Conclusion: Acute fetal hemorrhage from the rupture of aberrant
      fetal vessels often coincides with rupture of membranes. Identifying ruptured
      fetal vessels abnormally coursing through the chorioamniotic membranes on
      examination of the placenta provides supporting evidence for suspected fetal
      hemorrhage.

PMID- 30226733
TI  - Counseling and Management of a Conservatively Managed Second Trimester Cesarean
      Scar Pregnancy: A Case Report.
AB  - Background: Cesarean scar ectopic pregnancies (CSPs) are becoming more prevalent
      and can have an extremely poor prognosis, with high morbidity and mortality.
      Management guidelines for patients desiring conservative treatment should be
      established to improve outcomes. Case: A 33-year-old woman with a conservatively
      managed CSP now in the second trimester presented from an outside institution.
      After thorough counseling regarding potential maternal morbidity and extreme
      prematurity in the newborn based on clinical findings of progressive cervical
      shortening and vaginal spotting with a significant drop in hemoglobin, she
      abandoned conservative therapy and underwent a hysterectomy with the previable
      fetus in situ. Conclusion: As pregnancy progresses, danger to the mother and
      fetus can become severe and imminent. Progressive cervical shortening may be
      associated with much more significant bleeding than evidenced by spotting,
      indicating the importance of using cervical shortening in abandonment of
      conservative management to reduce impending morbidity and mortality.

PMID- 30226738
TI  - Orthogonal Ambipolar Semiconductors with Inherently Multi-Dimensional Responses
      for the Discriminative Sensing of Chemical Vapors.
AB  - Numerous examples of field-effect transistor (FET) biosensors and chemical
      sensors with good sensitivity and selectivity have now been developed. However,
      effectively discriminating between analytes has required either the use of
      receptors that selectively bind specific analytes or the fabrication of an array
      of sensors with varying but nonspecific responses. Both approaches exhibit
      significant limitations. In the first case, it can be difficult to design
      sufficiently specific receptors for many compounds, whereas the number of
      receptors required scales with the number of analytes to be detected, making it
      impractical to recognize many different compounds. In the second case, existing
      approaches to FET sensor arrays are generally material-inefficient and provide
      modest sensitivity. Here, we demonstrate that orthogonal ambipolar semiconductors
      consisting of semiconducting p-type polymers and n-type small-molecule nanowires
      with perpendicular in-plane orientations provide a platform with high sensitivity
      and inherently multi-dimensional response. This allows for discrimination between
      even closely related derivatives such as aromatic isomers and n-alkyl alcohols
      varying in length by a single carbon atom resolution using only a single sensor
      element.

PMID- 30226739
TI  - Multifunctional Supramolecular Materials Constructed from Polypyrrole@UiO-66
      Nanohybrids and Pillararene Nanovalves for Targeted Chemophotothermal Therapy.
AB  - Multifunctional supramolecular nanomaterials capable of targeted and multimodal
      therapy hold great potential to improve the efficiency of cancer therapeutics.
      Herein, we report a proof-of-concept nanoplatform for effective chemophotothermal
      therapy via the integration of folic acid-based active targeting and
      supramolecular nanovalves-based passive targeting. Inspired by facile surface
      engineering and designable layer-by-layer assembly concept, we design and
      synthesize PPy@UiO-66@WP6@PEI-Fa nanoparticles (PUWPFa NPs) to achieve efficient
      synergistic chemophotothermal therapy, taking advantage of the desirable
      photothermal conversion capability of polypyrrole nanoparticles (PPy NPs) and
      high drug-loading capacity of hybrid scaffolds. Significantly, pillararene-based
      pseudorotaxanes as pH/temperature dual-responsive nanovalves allow targeted drug
      delivery in pathological environment with sustained release over 4 days, which is
      complementary to photothermal therapy, and folic acid-conjugated
      polyethyleneimine (PEI-Fa) at the outmost layer through electrostatic
      interactions is able to enhance tumor-targeting and therapeutic efficiency. Such
      PUWPFa NPs showed efficient synergistic chemophotothermal therapy of cervical
      cancer both in vitro and in vivo. The present strategy offers not only the
      distinctly targeted drug delivery and release, but also excellent tumor
      inhibition efficacy of simultaneous chemophotothermal therapy, opening a new
      avenue for effective cancer treatment.

PMID- 30226740
TI  - Smart, Piezo-Responsive Polyvinylidenefluoride/Polymethylmethacrylate Surface
      with Triggerable Water/Oil Wettability and Adhesion.
AB  - The design of smart surfaces with externally triggerable water/oil wettability
      and adhesion represents one of the most up-to-date challenges in the field of
      material science. In this work, the intelligent surface with electrically
      triggerable wettability and water/oil adhesion is presented. As a basic material
      background exhibiting electric field (EF) sensitivity, the piezo-responsive
      polymethylmethacrylate/polyvinylidenefluoride polymer fibers were used. To expand
      the available range of water/oil contact angles (CAs) and adhesion, the fibers
      were grafted with hydrophilic or hydrophobic functional groups using diazonium
      chemistry. The fiber functionality was evaluated using the static CA and
      wettability hysteresis measurements (increasing/decreasing drop volume and
      tilting angles), drops adhesion/repellence and graphite self-cleaning test
      performed with and without the application of EF. It was found that the proposed
      method enables tuning the surface wettability in the
      superhydrophobic/superoleophobic-hydrophilic/oleophilic range and changing of
      surface properties from low adhesive to high adhesive for water and oil. More
      convincing results were achieved in the case of fiber surface modification by ADT
      C8F17, which may result from a rearrangement of the grated -C6H4C8F17 functional
      group under the application of EF triggering. Moreover, the triggering which can
      be performed in the extremely fast way (the surface responds to the EF switching
      on/off in seconds) was found to be fully reversible. Finally, the additional
      tests indicate the satisfactory stability of created fiber-based coating against
      the mechanical treatment.

PMID- 30226741
TI  - Microtubes with Complex Cross Section Fabricated by C-Shaped Bessel Laser Beam
      for Mimicking Stomata That Opens and Closes Rapidly.
AB  - This article presents a new method for fabricating complex cross-sectional
      microtubes with a high aspect ratio at micro/nanoscale. The microtubes are
      directly written in a photoresist using a femtosecond pulsed laser combined with
      a spatial light modulator (SLM). A new method for generating a C-shaped Bessel
      beam by modifying the Bessel beams with a SLM is reported for the first time.
      Using this gap-ring-shaped light field, microtubes with special cross section
      (trefoil-shaped, clover-shaped, spiral, etc.) have been first achieved through
      two-photo polymerization rapidly. The microtube wall can reach about 800 nm and
      the diameter of the gap-ring structure is only a few micrometers. As a
      demonstration, artificial stomata were manufactured with the same size as actual
      plants stomata consisting of gap-ring microtubes. This artificial stomata can
      mimic the function of the real stomata with rapid opening and closing,
      demonstrating its ability to trap and release microparticles regulated by rinse
      solvent.

PMID- 30226742
TI  - Calcium Phosphate Nanoparticles as Intrinsic Inorganic Antimicrobials: The
      Antibacterial Effect.
AB  - Cheap and simple to make, calcium phosphate (CP), thanks to its unusual
      functional pleiotropy, belongs to the new wave of abundant and naturally
      accessible nanomaterials applicable as a means to various technological ends. It
      is used in a number of industries, including the biomedical, but its intrinsic
      antibacterial activity in the nanoparticle form has not been sufficiently
      explored to date. In this study, we report on this intrinsic antibacterial effect
      exhibited by two distinct CP phases: an amorphous CP (ACP) and hydroxyapatite
      (HAp). The effect is prominent against a number of regular bacterial species,
      including Staphylococcus aureus, Staphylococcus epidermis, Enterococcus faecalis,
      Escherichia coli, and Pseudomonas aeruginosa, but also their multidrug-resistant
      (MDR) analogues. Although ACP and HAp displayed similar levels of activity
      against Gram-negative organisms, ACP proved to be more effective against the Gram
      positive ones, with respect to which HAp was mostly inert, yet this trend became
      reversed for the MDR strains. In addition to the intrinsic antimicrobial effect
      of CP nanoparticles, we have also observed a synergistic effect between the
      nanoparticles and certain antibiotics. Both forms of CP were engaged in a
      synergistic relationship with a variety of concomitantly delivered antibiotics,
      including ampicillin, kanamycin, oxacillin, vancomycin, minocycline,
      erythromycin, linezolid, and clindamycin, and enabled even antibiotics completely
      ineffective against particular bacterial strains to significantly suppress their
      growth. This relationship was complex; depending on a particular CP phase,
      bacterial strain and antibiotic, the antibacterial activity (i) intensified
      proportionally to the nanoparticle concentration, (ii) plateaued immediately
      after the introduction of nanoparticles in minute amounts, or (iii) exhibited
      concentration-dependent minima due to stress-induced biofilm formation. These
      findings present grounds for the further optimization of CP properties and
      maximization of this intriguing effect, which could in the long run make this
      material comparable in activity to the inorganics of choice for this application,
      including silver, copper, or zinc oxide, while retaining its superb safety
      profile and positive eukaryotic versus prokaryotic cell selectivity.

PMID- 30226743
TI  - A Cyclic Peptide Inhibitor of the iNOS-SPSB Protein-Protein Interaction as a
      Potential Anti-Infective Agent.
AB  - SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4 interact
      with inducible nitric oxide synthase (iNOS), causing the iNOS to be
      polyubiquitinated and targeted for degradation. Inhibition of this interaction
      increases iNOS levels, and consequently cellular nitric oxide (NO)
      concentrations, and has been proposed as a potential strategy for killing
      intracellular pathogens. We previously described two DINNN-containing cyclic
      peptides (CP1 and CP2) as potent inhibitors of the murine SPSB-iNOS interaction.
      In this study, we report the crystal structures of human SPSB4 bound to CP1 and
      CP2 and human SPSB2 bound to CP2. We then used these structures to design a new
      inhibitor in which an intramolecular hydrogen bond was replaced with a
      hydrocarbon linkage to form a smaller macrocycle while maintaining the bound
      geometry of CP2 observed in the crystal structures. This resulting pentapeptide
      SPSB-iNOS inhibitor (CP3) has a reduced macrocycle ring size, fewer nonbinding
      residues, and includes additional conformational constraints. CP3 has a greater
      affinity for SBSB2 ( KD = 7 nM as determined by surface plasmon resonance) and
      strongly inhibits the SPSB2-iNOS interaction in macrophage cell lysates. We have
      also determined the crystal structure of CP3 in complex with human SPSB2, which
      reveals the structural basis for the increased potency of CP3 and validates the
      original design.

PMID- 30226744
TI  - Identifying the Non-Identical Outermost Selenium Atoms and Invariable Band Gaps
      across the Grain Boundary of Anisotropic Rhenium Diselenide.
AB  - Rhenium diselenide (ReSe2) is a unique transition-metal dichalcogenide (TMDC)
      possessing distorted 1T structure with a triclinic symmetry, strong in-plane
      anisotropy, and promising applications in optoelectronics and energy-related
      fields. So far, the structural and physical properties of ReSe2 are mainly
      uncovered by transmission electron microscopy and spectroscopy characterizations.
      Herein, by combining scanning tunneling microscopy and spectroscopy (STM and STS)
      with first-principles calculations, we accomplish the on-site atomic-scale
      identification of the top four non-identical Se atoms in a unit cell of the
      anisotropic monolayer ReSe2 on the Au substrate. According to STS and
      photoluminescence results, we also determine the quasiparticle and optical band
      gaps as well as the exciton binding energy of monolayer ReSe2. In particular, we
      detect a perfect lattice coherence and an invariable band gap across the mirror
      symmetric grain boundaries in monolayer and bilayer ReSe2, which considerably
      differ from the traditional isotropic TMDCs featured with defect structures and
      additional states inside the band gap. Such essential findings should deepen our
      understanding of the intrinsic properties of two-dimensional anisotropic
      materials and provide fundamental references for their applications in related
      fields.

PMID- 30226745
TI  - Electrolyte Solvation Structure at Solid-Liquid Interface Probed by Nanogap
      Surface-Enhanced Raman Spectroscopy.
AB  - Understanding the fundamental factors that drive ion solvation structure and
      transport is key to design high-performance, stable battery electrolytes.
      Reversible ion solvation and desolvation are critical to the interfacial charge
      transfer process across the solid-liquid interface as well as the resulting
      stability of the solid electrolyte interphase. Herein, we report the study of Li+
      salt solvation structure in aprotic solution in the immediate vicinity (~20 nm)
      of the solid electrode-liquid interface using surface-enhanced Raman spectroscopy
      (SERS) from a gold nanoparticle (Au NP) monolayer. The plasmonic coupling between
      Au NPs produces strong electromagnetic field enhancement in the gap region,
      leading to a 5 orders of magnitude increase in Raman intensity for electrolyte
      components and their mixtures namely, lithium hexafluorophosphate, fluoroethylene
      carbonate, ethylene carbonate, and diethyl carbonate. Further, we estimate and
      compare the lithium-ion solvation number derived from SERS, standard Raman
      spectroscopy, and Fourier transform infrared spectroscopy experiments to monitor
      and ascertain the changes in the solvation shell diameter in the confined nanogap
      region where there is maximum enhancement of the electric field. Our findings
      provide a multimodal spectroscopic approach to gain fundamental insights into the
      molecular structure of the electrolyte at the solid-liquid interface.

PMID- 30226746
TI  - Carbon-Nanotube-Electrolyte Interface: Quantum and Electric Double Layer
      Capacitance.
AB  - We present a comprehensive study of the electrochemical capacitance between a one
      dimensional electronic material and an electrolyte. In contrast to a
      conventional, planar electrode, the nanoscale dimension of the electrode (with
      diameter smaller than the Debye length and approaching the size of the ions in
      solution) qualitatively changes the capacitance, which we measure and model
      herein. Furthermore, the finite density of states in these low dimensional
      electronic systems results in a quantum capacitance, which is comparable to the
      electrochemical capacitance. Using electrochemical impedance spectroscopy (EIS),
      we measure the ensemble average, complex, frequency dependent impedance (from 0.1
      Hz to 1 MHz) between a purified (99.9%) semiconducting nanotube network and an
      aqueous electrolyte (KCl) at different concentrations between 10 mM and 1 M. The
      potential dependence of the capacitance is convoluted with the potential
      dependence of the in-plane conductance of the nanotube network, which we model
      using a transmission-line model to account for the frequency dependent in-plane
      impedance as well as the total interfacial impedance between the network and the
      electrolyte. The ionic strength dependence of the capacitance is expected to have
      a root cause from the double layer capacitance, which we model using a modified
      Poisson-Boltzmann equation. The relative contributions from those two
      capacitances can be quantitatively decoupled. We find a total capacitance per
      tube of 0.67-1.13 fF/MUm according to liquid gate potential varying from -0.5 to 
      0.7 V.

PMID- 30226747
TI  - FAAH-Catalyzed C-C Bond Cleavage of a New Multitarget Analgesic Drug.
AB  - The discovery of extended catalytic versatilities is of great importance in both
      the chemistry and biotechnology fields. Fatty acid amide hydrolase (FAAH) belongs
      to the amidase signature superfamily and is a major endocannabinoid inactivating
      enzyme using an atypical catalytic mechanism involving hydrolysis of amide and
      occasionally ester bonds. FAAH inhibitors are efficacious in experimental models
      of neuropathic pain, inflammation, and anxiety, among others. We report a new
      multitarget drug, AGN220653, containing a carboxyamide-4-oxazole moiety and
      endowed with efficacious analgesic and anti-inflammatory activities, which are
      partly due to its capability of achieving inhibition of FAAH, and subsequently
      increasing the tissue concentrations of the endocannabinoid anandamide. This
      inhibitor behaves as a noncompetitive, slowly reversible inhibitor.
      Autoradiography of purified FAAH incubated with AGN220653, opportunely
      radiolabeled, indicated covalent binding followed by fragmentation of the
      molecule. Molecular docking suggested a possible nucleophilic attack by FAAH
      Ser241 on the carbonyl group of the carboxyamide-4-oxazole moiety, resulting in
      the cleavage of the C-C bond between the oxazole and the carboxyamide moieties,
      instead of either of the two available amide bonds. MRM-MS analyses only detected
      the Ser241-assisted formation of the carbamate intermediate, thus confirming the
      cleavage of the aforementioned C-C bond. Quantum mechanics calculations were
      fully consistent with this mechanism. The study exemplifies how FAAH structural
      features and mechanism of action may override the binding and reactivity
      propensities of substrates. This unpredicted mechanism could pave the way to the
      future development of a completely new class of amidase inhibitors, of potential
      use against pain, inflammation, and mood disorders.

PMID- 30226748
TI  - Defect Annihilation Pathways in Directed Assembly of Lamellar Block Copolymer
      Thin Films.
AB  - Defects in highly ordered self-assembled block copolymers represent an important
      roadblock toward the adoption of these materials in a wide range of applications.
      This work examines the pathways for annihilation of defects in symmetric diblock
      copolymers in the context of directed assembly using patterned substrates. Past
      theoretical and computational studies of such systems have predicted minimum free
      energy pathways that are characteristic of an activated process. However, they
      have been limited to adjacent dislocations with opposite Burgers vectors. By
      relying on a combination of advanced sampling techniques and particle-based
      simulations, this work considers the long-range interaction between dislocation
      pairs, both on homogeneous and nanopatterned substrates. As illustrated here,
      these interactions are central to understanding the defect structures that are
      most commonly found in applications and in experimental studies of directed self
      assembly. More specifically, it is shown that, for dislocation dipoles separated
      by several lamellae, multiple consecutive free energy barriers lead to effective
      kinetic barriers that are an order of magnitude larger than those originally
      reported in the literature for tightly bound dislocation pairs. It is also shown
      that annihilation pathways depend strongly on both the separation between
      dislocations and their relative position with respect to the substrate guiding
      stripes used to direct the assembly.

PMID- 30226749
TI  - A2-A1-D-A1-A2 Type Non-Fullerene Acceptors with 2-(1,1-Dicyanomethylene)rhodanine
      as the Terminal Groups for Poly(3-hexylthiophene)-Based Organic Solar Cells.
AB  - 2-(1,1-Dicyanomethylene)rhodanine (RCN) is an important electron-deficient
      terminal unit to build non-fullerene acceptors (NFAs) having been realized high
      power conversion efficiency (PCE) beyond 12% with complicated p-type polymer as
      electron donor. However, the photovoltaic properties of RCN-based NFAs are
      unsatisfied when paired with the classic p-type polymer poly(3-hexylthiophene)
      (P3HT). In order to make a contribution in this regard, we designed two RCN-based
      small molecular acceptors with A2-A1-D-A1-A2 structure, BT3 and BTA3, where
      benzothiadiazole (BT) and benzotriazole (BTA) are bridged A1 segments,
      respectively, to modulate the optoelectronic properties. As a result, P3HT:BTA3
      solar cell exhibits a promising PCE of 5.64%, with a VOC of 0.90 V and a fill
      factor (FF) of 0.65, which is obviously much better than that of P3HT:BT3 (PCE =
      2.55%, VOC = 0.72 V, FF = 0.61). The higher electron mobility of P3HT:BTA3 film
      indicates BTA3 tends to form a continuous pathway for electron transport even at
      a lower weight ratio of 1:0.3 than 1:0.5 for P3HT:BT3 film. Our results indicate
      that introducing a weak electron-withdrawing building block BTA is an effective
      strategy compared with the BT counterpart to improve the performance of RCN-based
      NFA devices.

PMID- 30226750
TI  - Mechanistic Evaluation of Lipopolysaccharide-Alexidine Interaction Using
      Spectroscopic and in Silico Approaches.
AB  - The increasing problem of multidrug resistance (MDR) in bacteria calls for
      discovery of new molecules and diagnostic methodologies that are effective
      against a wide range of microbial pathogens. We have studied the role of
      alexidine dihydrochloride (alex) as a bioaffinity ligand against
      lipopolysaccharide (LPS), a pathogen-associated surface marker universally
      present on all Gram-negative bacteria. While the activity of alex against
      bacteria is biologically known, little information exists on its mechanism of
      action or binding stoichiometry. We have used nuclear magnetic resonance (NMR),
      fluorescence, and surface plasmon resonance (SPR) spectroscopies to probe the
      binding characteristics of alex and LPS molecules. Our results indicate that
      LPS:alex stoichiometry lies between 1:2 and 1:4 and has a dissociation constant (
      KD) of 38 MUM that is mediated through electrostatic interactions between the
      negatively charged phosphate groups present on LPS and the positively charged
      guanidinium groups present in alex. Further, molecular dynamics (MD) simulations
      performed to determine the conformational interaction between the two molecules
      show good agreement with the experimental results, which substantiate the
      potential of alex molecule for LPS neutralization and hence, development of
      efficient in vitro diagnostic assays.

PMID- 30226751
TI  - Optical Signatures of Transiently Disordered Semiconductor Nanocrystals.
AB  - The optoelectronic properties of semiconductor nanocrystals (NCs) have led to
      efforts to integrate them as the active material in light-emitting diodes, solid
      state lighting, and lasers. Understanding related high carrier injection
      conditions is therefore critical as resultant thermal effects can impact optical
      properties. The physical integrity of NCs is indeed questionable as recent
      transient X-ray diffraction studies have suggested that nanoscopic particles
      reversibly lose crystalline order, or melt, under high fluence photoexcitation.
      Informed by such studies, here, we examine CdSe NCs under elevated fluences to
      determine the impact of lattice disordering on optical properties. To this end,
      we implement intensity-dependent transient absorption using both one- and two
      pump methods where the latter effectively subtracts out the NC optical signatures
      associated with lower fluence photoexcitation, especially band-edge features. At
      elevated fluences, we observe a long-lived induced absorption at a lower energy
      than the crystalline-NC bandgap across a wide range of sizes that follows power
      dependent trends and kinetics consistent with the prior transient X-ray
      measurements. NC photoluminescence studies provide further evidence that melting
      influences optical properties. These methods of characterizing bandgap narrowing
      caused by lattice disordering could facilitate routes to improved optical
      amplification and band-edge emission at high excitation density.

PMID- 30226752
TI  - In Pursuit of 2D Materials for Maximum Optical Response.
AB  - Despite being only a few atoms thick, single-layer two-dimensional (2D) materials
      display strong electron-photon interactions that could be utilized in efficient
      light modulators on extreme subwavelength scales. In various applications
      involving light modulation and manipulation, materials with strong optical
      response at different wavelengths are required. Using qualitative analytical
      modeling and first-principles calculations, we determine the theoretical limit of
      the maximum optical response such as absorbance ( A) and reflectance ( R) in 2D
      materials and also conduct a computational survey to seek out those with best A
      and R in various frequency ranges, from mid-infrared to deep-ultraviolet. We find
      that 2D boron has broadband reflectance R > 99% for >100 layers, surpassing
      conventional thin films of bulk metals such as silver. Moreover, we identify 2D
      monolayer semiconductors with maximum response, for which we obtain quantitative
      estimates by calculating quasiparticle energies and accounting for excitonic
      effects by solving the Bethe-Salpeter equation. We found several monolayer
      semiconductors with absorbances ?30% in different optical ranges, which are more
      than half of the maximum possible value, Alim = 1/2, for a freestanding 2D
      material. Our study predicts 2D materials which can potentially be used in
      ultrathin reflectors and absorbers for optoelectronic application in various
      frequency ranges.

PMID- 30226753
TI  - Large-Area Silver-Stibnite Nanoporous Plasmonic Films for Label-Free Biosensing.
AB  - The development of various plasmonic nanoporous materials has attracted much
      interest in different areas of research including bioengineering and biosensing
      because of their large surface area and versatile porous structure. Here, we
      introduce a novel technique for fabricating silver-stibnite nanoporous plasmonic
      films. Unlike conventional techniques that are usually used to fabricate
      nanoporous plasmonic films, we use a room-temperature growth method that is wet
      chemistry free, which enables wafer-scale fabrication of nanoporous films on
      flexible substrates. We show the existence of propagating surface plasmon
      polaritons in nanoporous films and demonstrate the extreme bulk refractive index
      sensitivity of the films using the Goos-Hanchen shift interrogation scheme. In
      the proof-of-concept biosensing experiments, we functionalize the nanoporous
      films with biotin-thiol using a modified functionalization technique, to capture
      streptavidin. The fractal nature of the films increases the overlap between the
      local field and the immobilized biomolecules. The extreme sensitivity of the Goos
      Hanchen shift allows femtomolar concentrations of streptavidin to be detected in
      real time, which is unprecedented using surface plasmons excited via the
      Kretschmann configuration.

PMID- 30226754
TI  - Flexible and Highly Sensitive Resistive Pressure Sensor Based on Carbonized Crepe
      Paper with Corrugated Structure.
AB  - Recently, cellulose paper based materials have emerged for applications in
      wearable "green" electronics due to their earth abundance, low cost, light
      weight, flexibility, and sustainability. Herein, for the first time, we develop
      an almost all cellulose paper based pressure sensor through a facile, cost
      effective, scalable, and environment-friendly approach. The screen-printed
      interdigital electrodes on the flat printing paper and the carbonized crepe paper
      (CCP) with good conductivity are integrated into a flexible pressure sensor as
      substrates and active materials, respectively. The porous and corrugated
      structure of the CCP endows the pressure sensor with high sensitivity (2.56-5.67
      kPa-1 in the range of 0-2.53 kPa), wide workable pressure range (0-20 kPa), fast
      response time (<30 ms), low detection limit (~0.9 Pa), and good durability (>3000
      cycles). Additionally, we demonstrate the practical applications of the CCP
      pressure sensor in detection of finger touching, wrist pulse, respiration,
      phonation, acoustic vibration, etc., and real-time monitoring of spatial pressure
      distribution. The proposed CCP pressure sensor has great potentials in various
      applications as wearable electronics. Moreover, the subtle fabrication of the
      desired materials based on commercially available products provides new insights
      into the development of green electronics.

PMID- 30226755
TI  - Multichannel-Structured Three-Dimensional Chip for Highly Sensitive Pathogenic
      Bacteria Detection Based on Fast DNA-Programmed Signal Polymerization.
AB  - The threat of food safety and the limited analytical methods with high
      performance promote the growing interest in the development of pathogenic
      bacteria biosensors. This study presents a pathogenic bacteria biosensing system,
      where a novel three-dimensional (3D) chip acts as an analytical carrier and DNA
      programmed hybridization chain reaction (HCR) causes signal amplification. The 3D
      chip is designed featuring a compact multichannel structure. It has a large
      surface area for sensitive sensing and exhibits multiple functions of target
      capture, separation, rinsing, and signal detection to simplify the analysis
      processes. HCR, which enables the fluorophore's polymerization, is designed as
      two signal amplification modes, each with unique advantages. Mode I achieves
      highly sensitive detection in a "sandwich" assay format, in which a long HCR
      amplified probe is used to boost the fluorescence signal. In mode II, the
      assembly of HCR is performed on the inner surface of the 3D chip. Especially, a
      group of rapid-assembly HCR sequences is proposed, of which the assembly time as
      short as 15 min stands out among the related works previously reported. Under the
      optimal conditions, the proposed biosensing system has the limits of detection
      (LOD) of 4 and 8 cfu/mL in mode I for Staphylococcus aureus detection and in mode
      II for Salmonella enterica Typhimurium detection, respectively. The specificity
      and the real sample applications are evaluated. This multichannel-structured 3D
      chip based on HCR signal amplification has potential applications in food safety
      monitoring and biosensor development.

PMID- 30226756
TI  - Maternal Transfer of Flame Retardants in Sharks from the Western North Atlantic
      Ocean.
AB  - The present work represents a comprehensive study of in utero maternal transfer
      of legacy and emerging flame retardants (FRs) in marine predators. We analyzed
      liver tissues from pregnant sharks of five viviparous species, including
      blacknose shark ( Carcharhinus acronotus; n = 12), blacktip shark ( Carcharhinus
      limbatus; n = 2), bonnethead ( Sphyrna tiburo; n = 2), Atlantic sharpnose shark (
      Rhizoprionodon terraenovae; n = 2), and spinner shark ( Carcharhinus brevipinna;
      n = 2), as well as their embryos ( n = 84 in total from five species), collected
      from the western North Atlantic Ocean. Concentrations of frequently detected
      emerging FRs in adult female blacknose sharks were determined to be 6.1-83.3 ng/g
      lipid weight (lw) for dechlorane analogues, 2.5-29.8 ng/g lw for tetrabromo- o
      chlorotoluene, and nondetection -32.6 ng/g lw for hexabromobenzene. These
      concentrations were 1-2 orders of magnitude lower than those of legacy
      polybrominated diphenyl ether flame retardants (85.7-398 ng/g lw). Similar
      contamination profiles were also found in the other four species, although FR
      concentrations varied in different species. A total of 21 FRs were commonly found
      in developing embryos of female sharks from five species, demonstrating maternal
      transfer in utero. The maternal transfer ratio (i.e., ratio of the mean litter
      concentration to their mother's concentration) determined in blacknose shark
      mother/embryo groups for each FR chemical was negatively associated with its
      octanol-water partition coefficient. Our work lays a solid foundation for future
      investigation of the underlying mechanisms of in utero transfer and additional
      physical or chemical factors that affect maternal transfer.

PMID- 30226757
TI  - Indoor (Photo)chemistry in China and Resulting Health Effects.

PMID- 30226759
TI  - A Heptanuclear Copper Iodide Nanocluster.
AB  - Nanoscale molecular clusters are attractive for the design of materials
      exhibiting original functions and properties. In particular, copper iodide
      clusters of high nuclearity are well-known for their stimuli-responsive
      luminescence properties. The synthesis and characterization of an unprecedented
      copper(I) iodide molecular cluster based on an original heptanuclear inorganic
      core are reported. This nanometer-size cluster is formulated as
      [Cu7I7(P(C6H4CF3)3)6(CH3CN)] and its novel structure has been characterized by X
      ray diffraction and multinuclear solid-state 63Cu, 31P, 13C, 19F, and 1H NMR
      spectroscopy. The photoluminescence properties of this cluster have been studied
      at variable temperature. Density functional theory calculations have been
      performed on this large molecular structure and allow one to rationalize the
      observed luminescence properties. This study highlights the crucial role of
      cuprophilic interactions in molecular copper iodide clusters for exhibiting
      photoactive properties.

PMID- 30226758
TI  - Clarifying the Copper Coordination Environment in a de Novo Designed Red Copper
      Protein.
AB  - Cupredoxins are copper-dependent electron-transfer proteins that can be
      categorized as blue, purple, green, and red depending on the spectroscopic
      properties of the Cu(II) bound forms. Interestingly, despite significantly
      different first coordination spheres and nuclearity, all cupredoxins share a
      common Greek Key beta-sheet fold. We have previously reported the design of a red
      copper protein within a completely distinct three-helical bundle protein,
      alpha3DChC2. (1) While this design demonstrated that a beta-barrel fold was not
      requisite to recapitulate the properties of a native cupredoxin center, the
      parent peptide alpha3D was not sufficiently stable to allow further study through
      additional mutations. Here we present the design of an elongated protein
      GRANDalpha3D (GRalpha3D) with Delta Gu = -11.4 kcal/mol compared to the original
      design's -5.1 kcal/mol. Diffraction quality crystals were grown of GRalpha3D (a
      first for an alpha3D peptide) and solved to a resolution of 1.34 A. Examination
      of this structure suggested that Glu41 might interact with the Cu in our
      previously reported red copper protein. The previous bis(histidine)(cysteine)
      site (GRalpha3DChC2) was designed into this new scaffold and a series of variant
      constructs were made to explore this hypothesis. Mutation studies around Glu41
      not only prove the proposed interaction, but also enabled tuning of the
      constructs' hyperfine coupling constant from 160 to 127 * 10-4 cm-1. X-ray
      absorption spectroscopy analysis is consistent with these hyperfine coupling
      differences being the result of variant 4p mixing related to coordination
      geometry changes. These studies not only prove that an Glu41-Cu interaction leads
      to the alpha3DChC2 construct's red copper protein like spectral properties, but
      also exemplify the exact control one can have in a de novo construct to tune the
      properties of an electron-transfer Cu site.

PMID- 30226760
TI  - Allele-Specific Isothermal Amplification Method Using Unmodified Self-Stabilizing
      Competitive Primers.
AB  - Rapid and specific detection of single nucleotide polymorphisms (SNPs) related to
      drug resistance in infectious diseases is crucial for accurate prognostics,
      therapeutics and disease management at point-of-care. Here, we present a novel
      amplification method and provide universal guidelines for the detection of SNPs
      at isothermal conditions. This method, called USS-sbLAMP, consists of SNP-based
      loop-mediated isothermal amplification (sbLAMP) primers and unmodified self
      stabilizing (USS) competitive primers that robustly delay or prevent unspecific
      amplification. Both sets of primers are incorporated into the same reaction
      mixture, but always targeting different alleles; one set specific to the wild
      type allele and the other to the mutant allele. The mechanism of action relies on
      thermodynamically favored hybridization of totally complementary primers,
      enabling allele-specific amplification. We successfully validate our method by
      detecting SNPs, C580Y and Y493H, in the Plasmodium falciparum kelch 13 gene that
      are responsible for resistance to artemisinin-based combination therapies
      currently used globally in the treatment of malaria. USS-sbLAMP primers can
      efficiently discriminate between SNPs with high sensitivity (limit of detection
      of 5 * 101 copies per reaction), efficiency, specificity and rapidness (<35 min)
      with the capability of quantitative measurements for point-of-care diagnosis,
      treatment guidance, and epidemiological reporting of drug-resistance.

PMID- 30226761
TI  - Correction to "Transfer Channel of Photoinduced Holes on a TiO2 Surface As
      Revealed by Solid-State Nuclear Magnetic Resonance and Electron Spin Resonance
      Spectroscopy".

PMID- 30226762
TI  - Exploration of Diverse Reactive Diad Geometries for Bifunctional Catalysis via
      Foldamer Backbone Variation.
AB  - What is the best spatial arrangement of a pair of reactive groups for
      bifunctional catalysis of a chemical transformation? The conformational
      versatility of proteins allows reactive group geometry to be explored and
      optimized via evolutionary selection, but it has been difficult for chemists to
      identify synthetic scaffolds that allow broad comparative evaluation among
      alternative reactive group geometries. Here we show that a family of helices,
      adopted predictably by oligomers composed partially or exclusively of beta-amino
      acid residues, enables us to explore a range of orientations for a pair of
      pyrrolidine units that must work in tandem to catalyze a crossed aldol reaction.
      Thus, the crossed aldol reaction serves as an assay of reactive diad efficacy. We
      have chosen a test reaction free of stereochemical complexity in order to
      streamline our study of reactivity. The best geometry enhances the initial rate
      of product formation by two orders of magnitude. Our findings raise the
      possibility that rudimentary catalysts involving an isolated secondary structure
      might have facilitated the development of prebiotic reaction networks.

PMID- 30226763
TI  - Dysprosium Compounds with Hula-Hoop-like Geometries: The Influence of Magnetic
      Anisotropy and Magnetic Interactions on Magnetic Relaxation.
AB  - Single-ion anisotropy is one of the crucial properties for mononuclear and even
      polynuclear single-molecule magnets (SMMs), which can be enhanced by the
      judicious choice of the coordination geometry around the metal centers.
      Meanwhile, magnetic interactions also play a significant role in high-performance
      polynuclear SMMs, especially the dinuclear SMMs. For exploring the influence of
      those two factors on the magnetic properties, we report a novel series of
      lanthanide complexes, [Dy(L)3(HL)(THF)2] (1), [Dy2(Py3CO)2(CF3SO3)4(H2O)2].CH3CN
      (2), and [Dy2(Py3CO)2(PhCOO)4(MeOH)2].MeOH (3), with hula-hoop-like geometries
      around the DyIII ions. All three complexes display slow relaxation of
      magnetization under a zero applied direct-current field with anisotropy barriers
      of 169 and 51 K for 1 and 3, respectively, while the slow relaxation of
      magnetization of complex 2 may mainly result from Raman relaxation. Besides,
      complex 1 demonstrates butterfly-type hysteresis below 4 K, and complex 2 shows
      no opening of the hysteresis loop with an inflection of around 0.25 T. Although
      complexes 2 and 3 have similar structures, the different coordinate anions induce
      distinct magnetic interaction states, antiferromagnetic and ferromagnetic for 2
      and 3, respectively. Ab initio calculations reveal that the better SMM behavior
      of complex 1 should be ascribed to stronger single-ion anisotropy compared with
      complexes 2 and 3. The small value of the dipolar interaction results in an
      overall antiferromagnetic interaction for complex 2, while the large value of the
      dipolar interaction causes an overall ferromagnetic interaction for complex 3,
      where the dipolar interactions are ferromagnetic for both complexes.

PMID- 30226765
TI  - Atroposelective Catalytic Asymmetric Allylic Alkylation Reaction for Axially
      Chiral Anilides with Achiral Morita-Baylis-Hillman Carbonates.
AB  - A highly efficient method to access axially chiral anilides through asymmetric
      allylic alkylation reaction with achiral Morita-Baylis-Hillman carbonates by
      using a biscinchona alkaloid catalyst was reported. Through the atroposelective
      approach, a broad range of axially chiral anilide products with different acyl
      groups, such as substituted phenyl, naphthyl, alkyl, enyl, styryl, and benzyl,
      were generated with very good yields, moderate to excellent cis: trans ratios,
      and good to excellent enantioselectivities. The reaction can be scaled up, and
      the synthetic utility of axially chiral anilides was proved by transformations.
      Moreover, the linear free energy relationship analysis was introduced to
      investigate the reaction.

PMID- 30226764
TI  - Counteranion Modulated Crystal Growth and Function of One-Dimensional Homochiral
      Coordination Polymers: Morphology, Structures, and Magnetic Properties.
AB  - Four pairs of enantiomeric dysprosium(III) phosphonates, namely, R- or S
      [Dy3(pempH2)2(pempH)7]2(NO3)4.12H2O ( R-1 or S-1), R- or S
      [Dy3(pempH)7(pempH2)2]Cl2.2H2O ( R-2 or S-2), R- or S
      [Dy3(pempH)7(pempH2)2]Br2.2H2O ( R-3 or S-3), and R- or S
      [Dy11(pempH2)6(pempH)27](CF3SO3)6.22H2O ( R-4 or S-4) are reported, where R- or S
      pempH2 represent R- or S-(1-phenylethyl)amino] methylphosphonic acid. All show
      homochiral chain structures, charge-balanced by counteranions. A comparison of
      the crystal morphologies of the R-isomers reveals that the overall shapes are
      quite similar for the four compounds, but the aspect ratio changes remarkably
      following the sequence: R-1 < R-2 < R-3 < R-4. The sequence is in agreement with
      the decreasing interchain interactions related to different counteranions, which
      is rationalized by molecular simulations. The counteranions also influence the
      intrachain structures and the local coordination environments of the DyIII ions.
      As a result, compounds R-2 and R-3 exhibit distinct dual relaxation processes at
      zero dc field with the effective energy barriers for the slow- and fast
      relaxation being 79.1 and 37.6 K for R-2, and 80.0 and 39.1 K for R-3,
      respectively. For compounds R-1 and R-4, however, slow magnetic relaxation is
      also observed at zero dc field but without the appearance of maxima down to 1.8
      K.

PMID- 30226766
TI  - Unveiling Biosynthesis of the Phytohormone Abscisic Acid in Fungi: Unprecedented
      Mechanism of Core Scaffold Formation Catalyzed by an Unusual Sesquiterpene
      Synthase.
AB  - Abscisic acid (ABA) is a well-known phytohormone that regulates abiotic stresses.
      ABA produced by fungi is also proposed to be a virulence factor of fungal
      pathogens. Although its biosynthetic pathway in fungi was proposed by a series of
      feeding experiments, the enzyme catalyzing the reaction from farnesyl diphosphate
      to alpha-ionylideneethane remains to be identified. In this work, we identified
      the novel type of sesquiterpene synthase BcABA3 and its unprecedented three-step
      reaction mechanism involving two neutral intermediates, beta-farnesene and
      allofarnesene. Database searches showed that BcABA3 has no homology with typical
      sesquiterpene synthases and that the homologous enzyme genes are found in more
      than 100 bacteria, suggesting that these enzymes form a new family of
      sesquiterpene synthases.

PMID- 30226767
TI  - Effect of Monoelectronic Oxidation of an Unsymmetrical Phenoxido-Hydroxido
      Bridged Dicopper(II) Complex.
AB  - A (MU-hydroxido, MU-phenoxido)CuIICuII complex 1 has been synthesized using an
      unsymmetrical ligand bearing an N, N-bis(2-pyridyl)methylamine (BPA) moiety
      coordinating one copper and a dianionic bis-amide moiety coordinating the other
      copper(II) ion. Electrochemical mono-oxidation of the complex in DMF occurs
      reversibly at 213 K at E1/2 = 0.12 V vs Fc+/Fc through a metal-centered process.
      The resulting species (complex 1+) is only stable at low temperature and has been
      spectroscopically characterized by UV-vis-NIR cryo-spectroelectrochemical and EPR
      methods. DFT and TD-DFT calculations, consistent with experimental data, support
      the formation of a CuIICuIII phenoxido-hydroxido complex. Low-temperature
      chemical oxidation of 1 by NOSbF6 yields a tetranuclear complex 2(SbF6)(NO2)
      which displays two binuclear CuIICuII subunits. The X-ray crystal structure of
      2(SbF6)(NO2) evidences that the nitrogen of the terminal amide group is
      protonated and the coordination of the amide occurs via the O atom. The bis-amide
      moiety appears to be a non-innocent proton acceptor along the redox process.
      Alternatively, protonation of complex 1 leads to the complex 2(ClO4)2, as
      evidenced by X-ray crystallography, cyclic voltammetry, and 1H NMR.

PMID- 30226768
TI  - Correction to "Tandem Catalysis: Transforming Alcohols to Alkenes by Oxidative
      Dehydroxymethylation".

PMID- 30226769
TI  - Photochemistry of SO2 at the Air-Water Interface: A Source of OH and HOSO
      Radicals.
AB  - The photochemistry of sulfur dioxide in the near UV-vis energy range has been
      studied in aqueous environments. The combination of previously reported
      experimental measurements with accurate quantum chemical calculations achieved in
      this work reveals that the process represents an important source of OH radicals
      in the troposphere. It implicates the reaction of the lowest triplet excited
      state of SO2 with a water molecule. When the process occurs in the gas-phase,
      photochemical OH production is only significant under high humidity conditions
      and high SO2 concentrations as those measured in polluted urban areas. However,
      the OH production rate increases by several orders of magnitude when the process
      takes place at the surface of water droplets. The present study indicates
      therefore that the atmospheric importance of sulfur dioxide goes beyond its well
      known role as acid rain and aerosol formation precursor.

PMID- 30226770
TI  - Unusually Reactive Cyclic Anhydride Expands the Scope of the Castagnoli-Cushman
      Reaction.
AB  - In the course of synthesizing and testing various "azole-including" cyclic
      anhydrides in the Castagnoli-Cushman reaction with imines, a remarkably reactive,
      pyrrole-based anhydride has been identified. It displayed a remarkably efficient
      reaction with N-alkyl and N-aryl imines, in particular, with "enolizable" alpha-C
      H imines which typically fail to react with a majority of known cyclic
      anhydrides. The reactivity of this anhydride has been justified by an efficient
      resonance stabilization of its enol form. This finding expands the existing
      arsenal of highly reactive cyclic anhydrides and further confirms the importance
      of anhydride enolization for an efficient Castagnoli-Cushman reaction.

PMID- 30226771
TI  - Photofragment Imaging, Spectroscopy, and Theory of MnO.
AB  - Density functional and ab initio calculations, along with photodissociation
      spectroscopy and ion imaging of MnO+ from 21,300 to 33,900 cm-1, are used to
      probe the photodissociation dynamics and bond strength of the manganese oxide
      cation (MnO+). These studies confirm the theoretical ground state (5Pi) and
      determine the spin-orbit constant ( A' = 14 cm-1) of the dominant optically
      accessible excited state (5Pi) in the region. Photodissociation via this excited
      5Pi state results in ground state Mn+ (7S) + O (3P) products. At energies above
      30,000 cm-1, the Mn+ (5S) + O (3P) channel is energetically accessible and
      becomes the preferred dissociation pathway. The bond dissociation energy ( D0 =
      242 +/- 5 kJ/mol) of MnO+ is measured from several images of each
      photofragmentation channel and compared to theory, resolving a disagreement in
      previous measurements. MRCI+Q calculations are much more successful in predicting
      the observed spectrum than TD-DFT or EOM-CCSD calculations.

PMID- 30226772
TI  - Achieving Superprotonic Conduction with a 2D Fluorinated Metal-Organic Framework.
AB  - A hydrolytically stable metal-organic framework (MOF) material, named KAUST-7',
      was derived from a structural phase change of KAUST-7 upon exposure to conditions
      akin to protonic conduction (363 K/95% relative humidity). KAUST 7' exhibited a
      superprotonic conductivity as evidenced by the impedance spectroscopic
      measurement revealing an exceptional conductivity up to 2.0 * 10-2 S cm-1 at 363
      K and under 95% RH, a performance maintained over 7 days. Ab initio molecular
      dynamics simulations suggested that the water-mediated proton transport mechanism
      is governed by water assisted reorganization of the H-bond network involving the
      fluorine moieties in KAUST-7' and the guest water molecules. The notable level of
      performances combined with a very good hydrolytic stability positions KAUST-7' as
      a prospective proton-exchange membrane alternative to the commercial benchmark
      Nafion. Furthermore, the remarkable RH sensitivity of KAUST-7' conductivity,
      substantially higher than previously reported MOFs, offers great opportunities
      for deployment as a humidity sensor.

PMID- 30226773
TI  - Bonding Motifs in Metal-Organic Compounds on Surfaces.
AB  - The bonds in metal organic networks on surfaces govern the resulting geometry as
      well as the electronic properties. Here, we study the nature of these bonds by
      forming phenazine-copper complexes on a copper surface by means of atomic
      manipulation. The structures are characterized by a combination of scanning probe
      microscopy and density functional theory calculations. We observed an increase of
      the molecule-substrate distance upon covalent bond formation and an out-of-plane
      geometry that is in direct contradiction with the common expectation that these
      networks are steered by coordination bonds. Instead, we find that a complex
      energy balance of hybridization with the substrate, inhomogeneous Pauli
      repulsion, and elastic deformation drives the phenazine-copper interaction. Most
      remarkably, this attractive interaction is not driven by electron acceptor
      properties of copper but is of completely different donation/back-donation
      mechanism between molecular pi-like orbitals and sp-like metal states. Our
      findings show that the nature of bonds between constituents adsorbed on surfaces
      does not have to follow the common categories.

PMID- 30226774
TI  - Evaluation of Ca2+ Binding Sites in Tacrolimus by Infrared Multiple Photon
      Dissociation Spectroscopy.
AB  - Tacrolimus (TAC) is an efficient immunosuppressant used in organ transplantation
      procedures. There is an intrinsic correlation between TAC and Ca2+ because of the
      dependence of its action mechanism on calcium and calcineurin, and the role of
      ion coordination on TAC identification and quantitation. To depict the Ca2+
      binding sites in TAC, this work carried out gas-phase vibrational infrared
      multiple photon dissociation spectroscopy of [Ca(TAC)]2+ and of three other TAC
      mimetic molecules (probes 1-3). Density functional theory (DFT) and Monte Carlo
      (MC) simulations were also used to support the experimental data assignment, and
      natural bond orbital (NBO) analysis was carried out to depict the coordination
      sphere. PM3 and B3LYP/6-31G(d) levels of theory displayed similar trends during
      the MC simulations, suggesting that PM3 is a viable alternative to more expensive
      DFT calculations, at least during the conformational analysis step. Infrared
      spectroscopy of the [Ca(probe X)1]2+ and [Ca(probe X)3]2+ ( X = 1-3) complexes
      allowed for a useful guide for building guess geometries and for the band
      assignment of the [Ca(TAC)]2+ complex. Nevertheless, the MC approach was
      particularly useful for exploring the potential energy surface. The lowest energy
      conformation for [Ca(TAC)]2+ was found by MC simulations and is 32.92 kJ mol-1
      lower in energy than the one found by comparing the results obtained for Ca2+
      coordination in probes, despite the calculated spectra being virtually identical.
      Both approaches are good ways to depict the coordination sites, and these results
      suggest that using small molecules as models is a reliable approach to depict the
      geometry or coordination sites of extensive ions, yielding a robust correlation
      between experimental and theoretical spectra. Furthermore, MC survey produced a
      lower energy conformation with a good match to the experimental results. Both
      methods depict the Ca2+ coordination sphere as a hexacoordinated environment
      where the main coordination centers are carbonyl groups.

PMID- 30226775
TI  - Droplet Mobility on Hydrophobic Fibrous Coatings Comprising Orthogonal Fibers.
AB  - Water droplet mobility on a hydrophobic surface cannot be guaranteed even when
      the droplet exhibits a high contact angle (CA) with the surface. In fact, droplet
      mobility on a surface, especially a fibrous surface, has remained an unsolved
      empirical problem. This paper is a combined experimental-computational study
      focused on droplet mobility on a fibrous surface. Electrospun polystyrene (PS)
      coatings were used in this work for their ability to exhibit high CAs
      simultaneously with low droplet mobility. To simplify this otherwise complicated
      problem and better isolate droplet-fiber interactions, the orientation of the
      fibers in the coatings was limited to the x and y directions. As the earth
      gravity was not strong enough to mobilize small droplets on PS coatings,
      experiments were conducted using ferrofluid droplets, and a magnet was used to
      make them move on the surface. Experimentally validated numerical simulations
      were used to enhance our understanding of the forces acting on a droplet before
      moving on the surface. Effects of Young-Laplace CA and fiber-fiber spacing on
      droplet mobility were investigated. In particular, it was found that droplet
      mobility depends strongly on the balance of forces exerted on the droplet by the
      fibers on the receding and advancing sides.

PMID- 30226776
TI  - Mechanism and Kinetics of the Gas-Phase Stereoinversion in Proteinogenic l
      Threonine and Its Astrophysical Relevance.
AB  - Quantum-mechanical computations are performed to trace the mechanistic pathways
      for the gas-phase stereoinversion in proteinogenic l-threonine, an amino acid
      with two stereocenters. The pathways are explored employing density functional
      and coupled cluster theories along with a global reaction route mapping strategy
      to locate various intermediates and transition states along the stereoinversion
      pathways on the complex potential energy surface of l-threonine. A simultaneous
      intramolecular proton and hydrogen atom transfer is observed to drive the
      stereoinversion in threonine. The kinetics analysis of the stereoinversion
      pathways is also carried out using transition state theory while accounting for
      the quantum mechanical tunnelling under conditions akin to various temperature
      regions of interstellar medium (ISM). The key step leading to stereoinversion
      through an achiral intermediate or transition state is predicted to involve a low
      energy barrier with high stereoinversion rates. The temperature region of 500
      1000 K corresponding to protoplanetary disks was found to be an optimum region
      for stereoinversion to occur in l-threonine with quite significant reaction
      rates. However, in the cold molecular clouds of ISM the stereoinversion is
      predicted to be a less likely event despite involving significant proton
      tunnelling. The stereoinversion pathways proposed in this work pay gainful
      insights, particularly, to the researchers looking for the complex organic
      molecules in outer space.

PMID- 30226777
TI  - Design, Characterization, and Biopharmaceutical Behavior of Nanoparticles Loaded
      with an HIV-1 Fusion Inhibitor Peptide.
AB  - New therapeutic alternatives to fight against the spread of HIV-1 are based on
      peptides designed to inhibit the early steps of HIV-1 fusion in target cells.
      However, drawbacks, such as bioavailability, short half-life, rapid clearance,
      and poor ability to cross the physiological barriers, make such peptides
      unattractive for the pharmaceutical industry. Here we developed, optimized, and
      characterized polymeric nanoparticles (NPs) coated with glycol chitosan to
      incorporate and release an HIV-1 fusion inhibitor peptide (E1) inside the vaginal
      mucosa. The NPs were prepared by a modified double emulsion method, and
      optimization was carried out by a factorial design. In vitro, ex vivo, and in
      vivo studies were carried out to evaluate the optimized formulation. The results
      indicate that the physicochemical features of these NPs enable them to
      incorporate and release HIV fusion inhibitor peptides to the vaginal mucosa
      before the fusion step takes place.

PMID- 30226778
TI  - 2,6-Bis(trifluoromethyl)phenylboronic Esters as Protective Groups for Diols: A
      Protection/Deprotection Protocol for Use under Mild Conditions.
AB  - The application of 2,6-bis(trifluoromethyl)phenyl boronic acid ( o-FXylB(OH)2; o
      FXyl = 2,6-(CF3)2C6H3) as a recoverable and reusable protective agent for diols
      is described. The resulting cyclic boronic esters are water- and air-stable and
      tolerant to various organic transformations. Moreover, they can be deprotected
      under mild conditions. This methodology was applied to the synthesis of a highly
      conjugated enetriyne natural product with anti-angiogenic activities.

PMID- 30226779
TI  - Photothermoelectric Detection of Gold Oxide Nonthermal Decomposition.
AB  - A thin coating of gold oxide, metastable at room temperature, can be formed by
      placing gold in a strongly oxidizing environment such as an oxygen plasma. We
      report scanning photovoltage measurements of lithographically defined gold
      nanowires subsequent to oxygen plasma exposure. Photovoltages are detected during
      the first optical scan of the devices that are several times larger than those
      mapped on subsequent scans. The first-scan enhanced photovoltage correlates with
      a reduction of the electrical resistance of the nanostructure back to preoxygen
      exposure levels. Repeating oxygen plasma exposure "reinitializes" the devices.
      These combined photovoltage and transport measurements imply that the enhanced
      photovoltage results from the photothermoelectric response of a junction between
      Au and oxidized Au, with an optically driven decomposition of the oxide.
      Comparisons with the known temperature-dependent kinetics of AuOx decomposition
      suggest that the light-driven decomposition is not a purely thermal effect. These
      experiments demonstrate that combined optical and electronic measurements can
      provide a window on surface-sensitive photochemical processes.

PMID- 30226780
TI  - Synthesis and Characterization of Cetuximab-Docetaxel and Panitumumab-Docetaxel
      Antibody-Drug Conjugates for EGFR-Overexpressing Cancer Therapy.
AB  - The safety and efficacy of anticancer antibody-drug conjugates (ADCs) depend on
      the selection of tumor-targeting monoclonal antibody (mAb), linker, and drug, as
      well as their specific chemical arrangement and linkage chemistry. In this study,
      we used a heterobifunctional cross-linker to conjugate docetaxel (DX) to
      cetuximab (CET) or panitumumab (PAN). The resulting ADCs were investigated for
      their in vitro EGFR-specific cytotoxicity and in vivo anticancer activity.
      Reaction conditions, such as reducing agent, time, temperature, and alkylation
      buffer, were optimized to yield potent and stable ADCs with consistent batch-to
      batch drug-to-antibody ratios (DARs). ADCs were synthesized with DARs from 0.4 to
      3.0, and all retained their EGFR affinity and specificity after modification.
      ADCs were sensitive to cell surface wildtype EGFR expression, demonstrating more
      cytotoxicity in EGFR-expressing A431 and MDA-MB-231 cell lines compared to U87MG
      cells. A431 tumor-bearing mice treated once weekly for four weeks with 100 mg/kg
      cetuximab-docetaxel ADC (C-SC-DX, DAR 2.5) showed durable anticancer responses
      and improved overall survival compared to the same treatment regimen with 1 mg/kg
      DX, 100 mg/kg CET, or a combination 1 mg/kg DX and 100 mg/kg CET. New treatment
      options are emerging for patients with both wild-type and mutated EGFR
      overexpressing cancers, and these studies highlight the potential role of EGFR
      targeted ADC therapies as a promising new treatment option.

PMID- 30226782
TI  - Ultrafast Pump-Repump-Probe Photochemical Hole Burning as a Probe of Excited
      State Reaction Pathway Branching.
AB  - We demonstrate pump-repump-probe (PRP) transient hole burning as a spectroscopic
      tool for differentiating reactive from nonreactive deactivation of excited
      photochemical reactants observed by transient absorption spectroscopy (TAS). This
      method utilizes a time-delayed, wavelength-tunable ultrafast pulse to alter the
      excited reactant population, with the impact of "repumping" quantified through
      depletions in photoproduct absorption. We apply this approach to characterize
      dynamics affecting the nonadiabatic photocyclization efficiency to form S0
      dihydrotriphenylene (DHT) following 266 nm excitation of ortho-terphenyl (OTP).
      TAS studies revealed bimodal deactivation of OTP*, but neither relaxation time
      scale (700 fs and 3.0 ps) could be assigned unambiguously to DHT formation due to
      overlap of excited-state and product spectra. PRP studies reveal that S1 OTP only
      cyclizes on the slower of these time scales, with the faster process attributable
      to nonreactive deactivation. We demonstrate that this method offers greater
      photochemical insights without assuming models to globally fit spectral
      transients collected by TAS.

PMID- 30226781
TI  - Increasing the Separation Capacity of Intact Histone Proteoforms Chromatography
      Coupling Online Weak Cation Exchange-HILIC to Reversed Phase LC UVPD-HRMS.
AB  - Top-down proteomics is an emerging analytical strategy to characterize
      combinatorial protein post-translational modifications (PTMs). However, sample
      complexity and small mass differences between chemically closely related
      proteoforms often limit the resolution attainable by separations employing a
      single liquid chromatographic (LC) principle. In particular, for ultramodified
      proteins like histones, extensive and time-consuming fractionation is needed to
      achieve deep proteoform coverage. Herein, we present the first online nanoflow
      comprehensive two-dimensional liquid chromatography (nLC*LC) platform top-down
      mass spectrometry analysis of histone proteoforms. The described two-dimensional
      LC system combines weak cation exchange chromatography under hydrophilic
      interaction LC conditions (i.e., charge- and hydrophilicity-based separation)
      with reversed phase liquid chromatography (i.e., hydrophobicity-based
      separation). The two independent chemical selectivities were run at nanoflows
      (300 nL/min) and coupled online with high-resolution mass spectrometry employing
      ultraviolet photodissociation (UVPD-HRMS). The nLC*LC workflow increased the
      number of intact protein masses observable relative to one-dimensional approaches
      and allowed characterization of hundreds of proteoforms starting from limited
      sample quantities (~1.5 MUg).

PMID- 30226783
TI  - Morphological Transition of Oppositely Charged Calix[4]arene Surfactant Mixture.
AB  - When a negatively charged sulfonic or a positively charged amine group is
      attached to calix[4]arene surfactants, denoted as SCal7 and QACal7, respectively,
      each system forms monodispersed spherical micelles with a defined aggregation
      number. We postulated that these defined monodisperse aggregations can be
      adjusted in terms of the coverage, that is, how efficiently can a spherical
      surface (, hydrophobic domain) be covered with identical caps (hydrophilic
      headgroup). We carried out small-angle X-ray scattering (SAXS), as well as
      titration calorimetry and dynamic light scattering (DLS), to observe the
      morphologies of the mixtures of these two components. The calorimetry showed a
      1:1 stoichiometric exothermic reaction with a rather large binding constant. This
      means that, once the twin is formed from QACal7 and SCal7, these components
      hardly separate. SAXS showed that the spherical micelles changed to cylindrical
      ones and then to vesicle shapes as the composition reached a ratio of 1:1. At
      some intermediate compositions, mixtures of cylinders and plates (or spheres)
      were observed, which were confirmed by dynamic light scattering. We assume that
      the twin has a larger packing parameter than the individuals because of the
      cancellation of the charges between the sulfonic and the amine groups, and thus,
      the increase of the twin composition induces the entire morphology change, as
      expected from the packing parameter principle. In the present case, the coverage
      may be a secondary factor determining the morphology.

PMID- 30226784
TI  - Chemical Ecogenomics-Guided Discovery of Phytotoxic alpha-Pyrones from the Fungal
      Wheat Pathogen Parastagonospora nodorum.
AB  - A biosynthetic gene cluster that is significantly upregulated in the fungal wheat
      pathogen Parastagonospora nodorum during plant infection was reconstructed
      heterologously in Aspergillus nidulans. This led to the discovery of five new
      alpha-pyrone polyketides, alternapyrones B-F (2-6). Compounds 5 and 6, which
      contain a highly substituted dihydrofuran, exhibited phytotoxicity on wheat seed
      germination. It is demonstrated that only three enzymes, one highly reducing
      polyketide synthase and two multifunctional P450 oxygenases, are needed to
      synthesize the structurally complex products.

PMID- 30226785
TI  - Human Serum Albumin and the p53-Derived Peptide Fusion Protein Promotes
      Cytotoxicity Irrespective of p53 Status in Cancer Cells.
AB  - Human serum albumin (HSA) fusion protein is a viable and effective approach to
      target and inhibit essential intracellular pathways. It has previously been shown
      that an HSA fusion protein containing a p53-reactivating peptide (rHSA-p53i)
      retains the binding activity to MDM2 and MDMX, resulting in p53 transcription
      dependent apoptosis. Here, we demonstrate that rHSA-p53i is able to bind and
      neutralize anti-apoptotic Bcl-2 family proteins, Bcl-xL and Mcl-1. This
      interaction displaces pro-apoptotic Bak and subsequently leads to intrinsic
      apoptosis via mimicking a p53 transcription-independent pathway. Cytotoxicity
      induced by rHSA-p53i, via p53 transcription dependent and independent apoptotic
      pathways, is irrespective of the p53 status in MDA-MB-231, HeLa, and SJSA-1 cells
      possessing either mutant, deficient, or wild-type p53. The therapeutic potential
      is also confirmed by treating SJSA-1 and MDA-MB-231 xenograft mouse tumors with
      rHSA-p53i. These data reveal that rHSA-p53i interferes with at least four
      intracellular targets, making it a viable therapeutic protein for the treatment
      of a variety of cancers, as well as a carrier to deliver fatty acid-modified
      chemotherapeutics.

PMID- 30226786
TI  - TLR4-Based Immunotherapeutics in Cancer: A Review of the Achievements and
      Shortcomings.
AB  - Toll-like Receptor 4 (TLR4) agonists have had a long journey in the field of
      cancer immunotherapy. Nevertheless, despite the remarkable number of the TLR4
      ligands that have gone through various preclinical and clinical stages, only two
      (Bacillus Calmette-Guerin (BCG) and monophosphoryl lipid A (MPLA)) have hitherto
      obtained the FDA approval for clinical application in cancer treatment. This
      paper provides a comprehensive review of the TLR4 agonists' journey as cancer
      active immunotherapeutics. Following a brief discussion of the rationale behind
      the use of TLR ligands in cancer immunotherapy, we will initially focus on the
      forerunner of the TLR4 agonists, bacterial lipopolysaccharide (LPS). Within this
      context, the potentials and shortcomings of immunotherapy with this agent will be
      addressed, the strategies that have been devised to enhance the associated
      therapeutic outcome will be discussed, and the consequent achievements and
      shortcomings will be summarized. Subsequently, further and perhaps less well
      known, molecular, bacterial, and viral TLR4 agonists with potential for cancer
      immunotherapy will be introduced, and if present, the outcome of the preclinical
      and clinical investigations of these agents will be reviewed. Finally, a look
      will be cast upon the promising souvenirs of the relatively new arena of
      nanotechnology, where TLR4 activating nanoparticulate systems will be proposed as
      potential candidates for the future development of this field.

PMID- 30226787
TI  - Blood-Brain Barrier Transport, Plasma Pharmacokinetics, and Neuropathology
      Following Chronic Treatment of the Rhesus Monkey with a Brain Penetrating
      Humanized Monoclonal Antibody Against the Human Transferrin Receptor.
AB  - A monoclonal antibody (mAb) against the blood-brain barrier (BBB) transferrin
      receptor (TfR) is a potential agent for delivery of biologic drugs to the brain
      across the BBB. However, to date, no TfRMAb has been tested with chronic dosing
      in a primate model. A humanized TfRMAb against the human (h) TfR1, which cross
      reacts with the primate TfR, was genetically engineered with high affinity (ED50
      = 0.18 +/- 0.04 nM) for the human TfR type 1 (TfR1). For acute dosing, the
      hTfRMAb was tritiated and injected intravenously (IV) in the Rhesus monkey, which
      confirmed rapid delivery of the humanized hTfRMAb into both brain parenchyma, via
      transport across the BBB, and into cerebrospinal fluid (CSF), via transport
      across the choroid plexus. For chronic dosing, a total of 8 adult Rhesus monkeys
      (4 males, 4 females) were treated twice weekly for 4 weeks with 0, 3, 10, or 30
      mg/kg of the humanized hTfRMAb via a 60 min IV infusion for a total of 8 doses
      prior to euthanasia and microscopic examination of brain and peripheral organs. A
      pharmacokinetics analysis showed the plasma clearance of the hTfRMAb in the
      primate was nonlinear, and plasma clearance was increased over 20-fold with
      chronic treatment of the low dose, 3 mg/kg, of the antibody. Chronic treatment of
      the primates with the 30 mg/kg dose caused anemia associated with suppressed
      blood reticulocytes. Immunohistochemistry of terminal brain tissue showed
      microglia activation, based on enhanced IBA1 immuno-staining, in conjunction with
      astrogliosis, based on increased GFAP immuno-staining. Moderate axonal/myelin
      degeneration was observed in the sciatic nerve. Further studies need to be
      conducted to determine if this neuropathology is induced by the antibody effector
      function, or is an intrinsic property of targeting the TfR in brain. The results
      indicate that chronic treatment of Rhesus monkeys with a humanized hTfRMAb may
      have a narrow therapeutic index, with associated toxicity related to microglial
      activation and astrogliosis of the brain.

PMID- 30226788
TI  - Self-Transport and Manipulation of Aqueous Droplets on Oil-Submerged Diverging
      Groove.
AB  - We report experimental study of self-transport of aqueous droplets along an oil
      submerged diverging groove structure. The migration phenomenon is illustrated,
      and the effect of various parameters such as droplet size d, oil layer thickness
      h, groove angle 2theta, and groove thickness delta on the droplet transport
      behavior (i.e., migration velocity and length) is investigated. Our study reveals
      that complete engulfment of aqueous droplets in the oil layer, that is attributed
      to a positive spreading parameter ( S > 0), is a prerequisite for the droplet
      transport. The results show that only droplets of diameter larger than the oil
      layer thickness (i.e., d >= h) get transported owing to a differential Laplace
      pressure between the leading and trailing faces of a droplet because of the
      diverging groove. Using experimental data, the variation of droplet migration
      velocity with distance along the diverging groove is correlated as U( x) = psi x
      0.9, where psi = d0.32theta-2.2 h-1.5delta0.7. The submerged groove structure was
      used to demonstrate simultaneous and sequential coalescence and transport of
      multiple droplets. Finally, the submerged groove structure was employed for
      extraction of aqueous droplets from oil. The proposed technique opens up a new
      avenue for evaporation and contamination free transport and coalescence of
      droplets for chemical and biological applications.

PMID- 30226789
TI  - Selective Oxidative Dearomatization of Angular Tetracyclic Phenols by Controlled
      Irradiation under Air: Synthesis of an Angucyclinone-Type Double Peroxide with
      Anticancer Properties.
AB  - Angular tetracyclic p-peroxyquinols, p-quinols, and a pentacyclic double
      peroxide, showing anticancer properties, were synthesized from the corresponding
      phenols by an environmentally friendly solvent- and wavelength-controlled
      irradiation under air in the absence of an external photosensitizer.

PMID- 30226790
TI  - An Examination of Relationships Among Resiliency, Hardiness, Affectivity, and
      Work-Life Balance in Collegiate Athletic Trainers.
AB  - CONTEXT: : A multilevel model has been used to describe the complex nature of
      work-life balance in sport organizations. Organizational aspects such as work
      scheduling, hours worked, job demands, and decreased perceived value have been
      reported as factors that can positively or negatively affect work-life balance.
      However, the individual factors that contribute to this balance have not been
      well studied. OBJECTIVE: : To better understand the individual factors (emotional
      stability and coping) that may facilitate or inhibit work-life balance among
      athletic trainers (ATs). DESIGN: : Cross-sectional online survey. SETTING: :
      National Collegiate Athletic Association athletic training setting. PATIENTS OR
      OTHER PARTICIPANTS: : A total of 423 (193 men, 230 women) ATs employed in the
      National Collegiate Athletic Association setting. MAIN OUTCOME MEASURE(S): : Data
      were collected via a Web-based survey instrument consisting of demographic and
      Likert-scale questions related to resiliency, hardiness, affectivity, work-family
      conflict (WFC), and work-family enrichment (WFE). Likert responses were summed
      and demographic information was analyzed for frequency and distribution.
      Independent t tests, analysis of variance, and Spearman correlations were
      calculated to evaluate the relationships among variables. RESULTS: : Participants
      exhibited moderate hardiness scores of 3.9 +/- 4.0 (range, -9 to 15). Positive
      affectivity was weakly negatively correlated with WFC ( r = -0.212, P < .001) and
      moderately positively correlated with WFE ( r = 0.448, P < .001). Resiliency was
      weakly negatively correlated with WFC ( r = -0.25, P < .001) and weakly
      positively correlated with WFE ( r = 0.228, P < .001). Additionally, individuals
      with less than 10 years of experience had lower positive affectivity scores than
      those with more than 10 years of experience. Men scored higher than women only in
      resiliency. CONCLUSIONS: : Collegiate ATs demonstrated moderate levels of coping
      behaviors that allow them to manage their personal and professional lives.
      Athletic trainers with more years of experience displayed a more positive affect.

PMID- 30226791
TI  - Spending on Antineoplastic Agents in the United States, 2011 to 2016.
AB  - PURPOSE:: Recent cancer drug approvals are lauded as being more effective with
      relatively fewer adverse effects, but these treatments come with a great cost to
      the US health care system. There is little information on recent trends in actual
      antineoplastic expenditures representative of the whole US health care system or
      by sector. Therefore, the objective of this study was to describe antineoplastic
      expenditures in the United States by year and sector. METHODS:: This was a
      retrospective, cross-sectional study of IQVIA (formerly QuintilesIMS) National
      Sales Perspective data for the period of January 1, 2011, to December 31, 2016.
      Actual expenditures were totaled by health care sector and calendar year, then
      adjusted for medical-cost inflation to 2016 dollars. Growth was calculated as the
      percentage increase from the previous year. RESULTS:: Total expenditures of
      antineoplastic agents across all channels grew from $26.8 billion in 2011 to
      $42.1 billion in 2016. Antineoplastic spending increased 12.2% in 2016 (compared
      with the previous year), followed by 15.6% in 2015, 13.4% in 2014, 6.3% in 2013,
      and 0.4% in 2012. Throughout the study period, 96.5% of total antineoplastic
      expenditures occurred within clinics, mail-order pharmacies, nonfederal
      hospitals, and retail pharmacies. CONCLUSION:: Antineoplastic expenditures are
      expected to increase because of continuing development and approval of costly
      targeted cancer therapies. Cost containment and utilization management strategies
      must be balanced so as not to restrict access or disrupt innovation. Future
      policies should focus on ensuring safe and appropriate use of antineoplastics
      while balancing long-term drug costs.

PMID- 30226792
TI  - Speech Is Silver, Nonverbal Behavior Is Gold: How Implicit Partner Evaluations
      Affect Dyadic Interactions in Close Relationships.
AB  - Growing evidence suggests that the seeds of relationship decay can be detected
      via implicit partner evaluations even when explicit evaluations fail to do so.
      However, little is known about the concrete daily relational processes that
      explain why these gut feelings are such important determinants of relationships'
      long-term outcomes. The present integrative multimethod research yielded a novel
      finding: that participants with more positive implicit partner evaluations
      exhibited more constructive nonverbal (but not verbal) behavior toward their
      partner in a videotaped dyadic interaction. In turn, this behavior was associated
      with greater satisfaction with the conversation and with the relationship in the
      following 8-day diary portion of the study. These findings represent a
      significant step forward in understanding the crucial role of automatic processes
      in romantic relationships. Together, they provide novel evidence that
      relationship success appears to be highly dependent on how people spontaneously
      behave in their relationship, which may be ultimately rooted in their implicit
      partner evaluations.

PMID- 30226793
TI  - College-Bound: Transition Planning Strategies for Students With Type 1 Diabetes.
AB  - Transition planning is mandated for students who receive special education
      services; however, it is not required for students with chronic conditions.
      Students with chronic conditions nearing graduation would benefit from more
      intensive attention to their post-high school self-care needs and
      responsibilities. Students with type 1 diabetes must be able to understand the
      necessary self-care of one of the most complicated and intensive chronic
      conditions yet there are no evidence-based strategies for how to help students
      transition from the support provided at school to independence at graduation. The
      need for a student with type 1diabetes to independently manage their diabetes is
      even greater as the student leaves home for college. School nurses, who are also
      certified diabetes educators, created a support group for seniors with type 1
      diabetes. The group focused on life after high school and provided the students
      with a detailed checklist to help improve knowledge and prepare students for the
      transition to college. Participants felt better prepared to move on to college
      armed with their checklist and other resources to help when away from home.

PMID- 30226794
TI  - Bench and pilot scale performance assessment of recycled membrane converted from
      old nanofiltration membranes.
AB  - Recycling of end-of-life polyamide-based thin film composite (TFC) membranes is
      gaining interest in academic and industrial contexts. The effects of chlorine
      exposure on the performance of polyamide membranes result in an increase in
      membrane permeability, whereas the solute rejection decreases. Therefore, the
      controlled chemical conversion of old reverse osmosis (RO) membranes has been
      reported by some previous papers. The objectives of this study were to assess
      recycling of old nanofiltration (NF) membrane, to assess the performance of the
      recycled membranes for a river water treatment application, and to conduct
      preliminary cost evaluations. Recycling technique consisted of exposing the
      membrane to a sodium hypochlorite solution in order to remove its polyamide layer
      and conversion to a low-pressure membrane. The work conducted bench scale and
      long-time pilot tests, and the recycled membranes showed a low fouling tendency.
      The difference between some results in bench- and pilot scale underscores the
      importance of evaluating design parameters using pilot scale units. Based on the
      cost analysis, the total cost of chemical recycling end-of-line NF membranes for
      a river water treatment is approximately 1.1% of the cost of using a new UF
      membrane. There is a great potential in using recycled membranes for rivers water
      treatments.

PMID- 30226795
TI  - C-reactive Protein in HPV-Positive and HPV-Negative Oropharyngeal Cancer.
AB  - Objective Evaluate serum C-reactive protein (CRP) in human papillomavirus (HPV)
      positive oropharynx cancer as compared with HPV-negative oropharynx cancer and
      determine if CRP levels were associated with overall survival and/or recurrence
      free survival. Study Design Prospective cohort study. Setting Tertiary care
      academic cancer center between 2007 and 2010. Subjects and Methods Among patients
      with oropharynx cancer and confirmed HPV status, plasma CRP levels were measured
      with a high-sensitivity ELISA kit. Multivariable logistic regression analysis
      compared 4 categories of CRP (low, moderate, high, very high) between the HPV
      positive and HPV-negative groups. Kaplan-Meier methods and Cox regression models
      were used to determine overall survival and recurrence-free survival by CRP level
      in both populations. Results Between 113 HPV-positive and 110 HPV-negative
      patients, CRP levels were significantly higher in the HPV-positive group, but
      these levels did not demonstrate a statistically significant dose-response trend.
      Higher CRP levels were also associated with reduced overall survival ( P = .016)
      and recurrence-free survival ( P < .001) within the HPV-negative group in
      univariable analysis; in multivariate analysis, the comparisons were not
      significantly different. Within HPV-positive oropharynx cancer, CRP levels were
      not significantly associated with overall survival or recurrence-free survival in
      univariable or multivariable analyses. Conclusion Circulating CRP was higher in
      HPV-positive versus HPV-negative oropharynx cancer. Among HPV-negative patients,
      higher CRP levels were associated with reduced survival.

PMID- 30226796
TI  - A Transitional Probability Model for Parkinson's Disease Motor States With
      Applications to Missing Data.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder
      with significant disability. Subjects with advanced PD often suffer from motor
      complications that may interfere significantly with their daily activities.
      Levodopa (LD) in combination with a dopa decarboxylase inhibitor such as
      carbidopa (CD) is considered the gold standard in the treatment of PD. However,
      long-term treatment with LD often leads to the development of motor
      complications. Motor complications include motor fluctuations and dyskinesia.
      Motor fluctuations are states where the subject cycles between periods of "on"
      state where subjects are in improved mobility and "off" state where subjects are
      in impaired mobility. Dyskinesia are the involuntary and irregular twisting
      and/or turning movements. METHODS: A Markov transitional probability model is
      proposed to estimate the likelihood of staying in one state versus transitioning
      from one state to another. RESULTS: An application of the model to an example
      from a clinical trial investigating the effect of an extended-release carbidopa
      levodopa (CD-LD) product versus an immediate-release CD-LD product is
      illustrated. CONCLUSION: A Markov transitional probability model can be used to
      model the likelihood of staying in one state versus transitional from one state
      to another. The model can also be used as a basis for multiple imputation of
      missing data.

PMID- 30226797
TI  - Catalytic oxidative desulphurization of gasoline using amphiphilic
      polyoxometalate@polymer nanocomposite as an efficient, reusable, and green
      organic-inorganic hybrid catalyst.
AB  - To preparation of ultra-clean gasoline fuel, a new amphiphilic nanocomposite (TBA
      SiWMn@PVA) has been successfully synthesized by supporting sandwich-type
      silicotungstate polyoxometalate ((n-C4H9)4N)7H5Si2W18Mn4O68 (TBA-SiWMn) on
      polyvinylalcohol (PVA) as an efficient catalyst for catalytic oxidative
      desulphurization (CODS) of gasoline. The synthesized materials were characterized
      by means of elemental analysis, 113Mn NMR, 29Si NMR, XRD, SEM, FT-IR and UV-vis
      techniques. The catalytic activity of TBA-SiWMn@PVA nanocomposite was tested on
      real gasoline in the presence of CH3COOH/H2O2 as an oxidant and the results were
      compared with model sulphur compounds at the same conditions. The TBA-SiWMn@PVA
      nanocomposite was shown excellent catalytic performance and recoverability for
      ODS of gasoline with high yield. The effects of the reaction time, reaction
      temperature, dosage and nature of catalyst were investigated. The reaction
      mechanism and the kinetic parameters of sulphur compounds oxidation were also
      discussed. The probable mechanism was proposed via the electrophilic mechanism
      through the formation of a peroxometalate intermediate complex with phase
      transfer properties. Results were indicated that the kinetics of sulphur
      oxidation fitted the pseudo-first-order kinetic model. After 5 oxidation runs,
      the heterogeneous nanocatalyst was separated and recovered easily.

PMID- 30226798
TI  - Bronchoscopy for Pediatric Airway Foreign Body: Thirty-Day Adverse Outcomes in
      the ACS NSQIP-P.
AB  - Objectives (1) Describe outcomes of bronchoscopy with foreign body removal among
      children on the basis of a large standardized multi-institutional data set. (2)
      Identify factors associated with 30-day adverse events. Study Design Cross
      sectional analysis of a US national database. Setting Public data set from the
      ACS NSQIP-P (American College of Surgeons National Surgical Quality Improvement
      Program-Pediatric) from 2012 to 2015. Subjects and Methods Children <18 years old
      who underwent bronchoscopy with removal of foreign body were identified. Patient
      demographics, comorbidities, hospitalization factors, surgical characteristics,
      and 30-day postoperative adverse events, including complication and readmission,
      were analyzed. Multivariate logistic regression identified predictive factors for
      postoperative complications and prolonged length of stay. Results A total of 275
      children underwent bronchoscopic foreign body removal (n = 165 male, 60%; n = 75
      nonwhite and/or Hispanic, 27%; mean age, 3.5 years [range, 0.63-17.9; median,
      2.0]). Adverse events occurred among 10 children (4%). Seven had pulmonary
      related complications, and 1 patient died. Three patients were readmitted; there
      were no reoperations. On multivariate analysis, preoperative pulmonary disease or
      need for pulmonary support (odds ratio [OR], 6.42; P = .04) predicted
      postoperative complications. Preoperative pulmonary compromise (OR, 8.10; P <
      .01), American Society of Anesthesiologists class 3 or 4 (OR, 4.13; P < .01), and
      prolonged operative time (OR, 3.05; P = .01) were associated with prolonged
      hospital stay. Conclusion Bronchoscopy for retrieval of foreign body among
      children has an overall low incidence of 30-day adverse events. Children with
      preoperative pulmonary compromise have a significantly higher risk of
      postoperative complications. These findings may be applied to optimize
      perioperative care and counsel parents and families.

PMID- 30226799
TI  - Managing the Risks of Medicines: An Examination of FDA's Application of Criteria
      for Requiring a REMS.
AB  - BACKGROUND: In September 2016, the Food and Drug Administration (FDA) published a
      draft guidance for industry, FDA's Application of Statutory Factors in
      Determining When a REMS Is Necessary, that detailed the factors the Agency
      considers in determining when a Risk Evaluation and Mitigation Strategy (REMS) is
      necessary. The objective of this study was to determine how the FDA has applied
      these criteria for newly approved drugs. METHODS: For the 3-year period, 2015
      2017, which included a full year of FDA approvals both before and after the
      issuance of the draft guidance, publicly available FDA reviews were analyzed for
      all 113 approved products using the criteria outlined in the guidance. RESULTS:
      Of the 113 products approved, 5 required a REMS. The most cited reasons for not
      requiring a REMS for the remaining 108 drugs were that risks could be managed via
      professional labeling (87%), physicians (primarily specialists) were familiar
      with the management of the risks (76%), the risk profile was similar to other non
      REMS marketed products (45%), products were used in a controlled setting
      (inpatient, infusion center) (30%), and/or safety concerns would be further
      evaluated by a postmarket study (14%). CONCLUSIONS: A review of Agency risk
      evaluations indicate that whether physicians are sufficiently familiar with and
      capable of managing a risk and that the health care setting where the product is
      administered is conducive to such management are leading factors in determining
      whether or not to require a REMS.

PMID- 30226800
TI  - Health Assessment of Free-Ranging Chelonians in an Urban Section of the Bronx
      River, New York.
AB  - The Bronx River in Bronx, New York spans an area of significant human development
      and has been subject to historic and ongoing industrial contamination. We
      evaluated the health of free-ranging native common snapping turtles ( Chelydra
      serpentina) and nonnative invasive red-eared sliders ( Trachemys scripta) in a
      segment of the Bronx River between May and July 2012. In 18 snapping turtles and
      nine sliders, complete physical examinations were performed, ectoparasites
      collected, and blood was analyzed for contaminants (mercury, thallium, cadmium,
      arsenic, lead, selenium, oxychlordane, alpha-chlordane, dieldrin,
      dichlorodiphenyldichloroethane [DDD], dichlorodiphenyldichloroethylene [DDE],
      polychlorinated biphenyls). Complete blood counts and the presence of
      hemoparasites were determined in 16 snapping turtles and nine sliders. Swabs of
      the choana and cloaca were screened for ranavirus, adenovirus, herpesvirus, and
      Mycoplasma spp. by PCR in 39 snapping turtles and 28 sliders. Both turtle species
      exhibited bioaccumulation of various environmental contaminants, particularly
      organochlorines and polychlorinated biphenyls. Molecular screening revealed a
      unique herpesvirus in each species. A Mycoplasma sp. previously isolated from
      emydid turtles was detected in red-eared sliders while a unique Mycoplasma sp.
      was identified in common snapping turtles. Ranaviruses and adenoviruses were not
      detected. Our study established a baseline health assessment to which future data
      can be compared. Moreover, it served to expand the knowledge and patterns of
      health markers, environmental contaminants, and microorganisms of free-ranging
      chelonians.

PMID- 30226801
TI  - Detection of Rabbit Hemorrhagic Disease Virus GI.2/RHDV2/B in the Mediterranean
      Pine Vole ( Microtus duodecimcostatus) and White-Toothed Shrew ( Crocidura
      russula).
AB  - The European wild rabbit ( Oryctolagus cuniculus) is a key prey species on the
      Iberian Peninsula, and several predator species that are at risk of extinction
      are dependent on them as prey. A new rabbit hemorrhagic disease (RHD) virus
      genotype (GI.2/RHDV2/b) emerged in 2010 and posed a threat to wild rabbit
      populations. During a survey aimed at investigating RHD epidemiology in wild
      rabbits, GI.2/RHDV2/b was detected by duplex real-time PCR in carcasses of one
      Mediterranean pine vole ( Microtus duodecimcostatus) and two white-toothed shrews
      ( Crocidura russula). Laboratory New Zealand white rabbits that were challenged
      with inocula obtained from the liver of the small mammals died showing RHD
      lesions, confirming the infectiousness of the isolates. Phylogenetic analysis of
      the VP60 gene nucleotide sequences showed complete homology between the isolates
      from the two small mammal species and a high degree of similarity, but not
      complete homology, to GI.2/RHDV2/b sequences from wild rabbits. The GI.2/RHDV2/b
      genotype has not been reported in species outside the order Lagomorpha.

PMID- 30226802
TI  - Knemidokoptiasis in a Wild Bird, the Little Spiderhunter ( Arachnothera
      longirostra cinireicollis), in Sumatra, Indonesia.
AB  - We report knemidokoptiasis in a wild male Little Spiderhunter ( Arachnothera
      longirostra cinireicollis; family Nectariniidae; order Passeriformes) from Jambi,
      Sumatra, Indonesia, in September 2017. Microscopic examination of a scraping from
      its leg lesion revealed the presence of Knemidocoptes jamaicensis as the cause of
      the condition.

PMID- 30226803
TI  - Isolation of Rabies Virus from the Salivary Glands of Wild and Domestic
      Carnivores during a Skunk Rabies Epizootic.
AB  - Rabies is a fatal zoonotic disease of global importance. Rabies virus is shed in
      the saliva of infected hosts and is primarily transmitted through bite contact.
      Canine rabies has been eliminated from the US, but wildlife constitutes more than
      90% of the reported cases of animal rabies in the US each year. In the US,
      several wild carnivore species are reservoirs of distinct variants of rabies
      virus (RV). After decades of apparent absence, the south-central skunk (SCSK) RV
      variant was detected in Colorado in 2007 and resulted in a large-scale epizootic
      in striped skunk ( Mephitis mephitis) populations in northern Colorado starting
      in 2012. We attempted isolation of RV from salivary gland tissues from confirmed
      rabid carnivores, comprising 51 striped skunks and seven other wild and domestic
      carnivores collected during 2013 through 2015 in northern Colorado. We isolated
      RV from 84.0% (158/188; 95% CI=78.1-88.6%) of striped skunk and 71% (17/24; 95%
      CI=51-85%) of other carnivore salivary glands. These data suggested that infected
      reservoir and vector species were equally likely to shed the SCSK RV variant and
      posed a secondary transmission risk to humans and other animals.

PMID- 30226805
TI  - Fourteen-Pound Fluvoxamine-Associated Weight Gain in a Young Woman with
      Depression and Multiple Anxiety Symptoms.

PMID- 30226806
TI  - From the Editor-in-Chief's Desk.

PMID- 30226807
TI  - Improving diagnosis, reperfusion therapy and secondary prevention in acute
      myocardial infarction.

PMID- 30226808
TI  - Long noncoding RNA LINC00261 induces chemosensitization to 5-fluorouracil by
      mediating methylation-dependent repression of DPYD in human esophageal cancer.
AB  - Approximately 85% of a single administered dose of 5-fluorouracil (5-FU) will be
      degraded by dihydropyrimidine dehydrogenase (DYPD). Studies have highlighted a
      link between the complete or partial loss of DYPD function and clinical responses
      to 5-FU; however, the underlying molecular basis of DPD deficiency remains poorly
      understood. Hence, the aim of the present study was to evaluate the prevailing
      hypothesis which suggests that overexpression of LINC00261 possesses the ability
      to modulate the methylation-dependent repression of DPYD, ultimately resulting in
      an elevation of the sensitivity of human esophageal cancer cells to 5-FU.
      LINC00261 levels were initially quantified, followed by analysis of DYPD
      methylation within the cancerous tissues collected from 75 patients diagnosed
      with esophageal cancer undergoing 5-FU-based adjuvant chemotherapy. In an attempt
      to determine the levels of LINC00261 related to the esophageal cancer cell
      resistance to 5-FU and to identify the interaction between the levels of
      LINC00261 and methylation of the DYPD promoter, esophageal cancer cells TE-1 and 
      5 were prepared, in which LINC00261 and the 5-FU-resistant TE-1 and -5 cells were
      overexpressed. The levels of LINC00261 were reduced among the cancerous tissues
      obtained from patients exhibiting resistance to 5-FU. Overexpression of LINC00261
      was determined to dramatically inhibit proliferation and resistance to apoptosis
      among 5-FU-resistant TE-1 and -5 cells, whereas silencing of LINC00261 was
      determined to enhance proliferation and resistance to apoptosis among the TE-1
      and -5 cells. DPYD, a confirmed target of LINC00261, displayed a greater
      incidence of DNA methylation among patient's sensitive to 5-FU. A key finding
      revealed that overexpressed LINC00261 could increase the methylation of the DPYD
      promoter through the recruitment of DNA methyltransferase (DNMT), which, in turn,
      acts to decrease DPYD activity in 5-FU-resistant TE-1 cells, whereas a reversible
      change was recorded once the demethylation reagent 5-aza-2'-deoxyctidine was
      employed to treat the 5-FU-resistant TE-1 cells. Taken together, the results of
      the study provided evidence emphasizing the distinct antitumor ability of
      LINC00261 in cases of esophageal cancer, which was manifested by overexpression
      of LINC00261 detected to increase the sensitivity of human esophageal cancer
      cells to 5-FU by mediating methylation-dependent repression of DPYD. Our study
      highlighted the potential of LINC00261 as a novel target capable of improving the
      chemotherapeutic response and survival of patients with esophageal cancer.-Lin,
      K., Jiang, H., Zhuang, S.-S., Qin, Y.-S., Qiu, G.-D., She, Y.-Q., Zheng, J.-T.,
      Chen, C., Fang, L., Zhang, S.-Y. Long noncoding RNA LINC00261 induces
      chemosensitization to 5-fluorouracil by mediating methylation-dependent
      repression of DPYD in human esophageal cancer.

PMID- 30226809
TI  - Extracellular vesicles derived from human umbilical cord mesenchymal stem cells
      alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress
      and neutrophil inflammatory response.
AB  - Mesenchymal stem cells (MSCs) have been reported to exert therapeutic effects on
      immunoregulation, tissue repair, and regeneration from the bench to the bedside.
      Increasing evidence demonstrates that extracellular vesicles (EVs) derived from
      MSCs could contribute to these effects and are considered as a potential
      replacement for stem cell-based therapies. However, the efficacy and underlying
      mechanisms of EV-based treatment in hepatic ischemia-reperfusion injury (IRI)
      remain unclear. Here, we demonstrated that human umbilical cord MSC-EVs (huc-MSC
      EVs) could protect against IRI-induced hepatic apoptosis by reducing the
      infiltration of neutrophils and alleviating oxidative stress in hepatic tissue in
      vivo. Meanwhile, huc-MSC-EVs reduced the respiratory burst of neutrophils and
      prevented hepatocytes from oxidative stress-induced cell death in vitro.
      Interestingly, we found that the mitochondria-located antioxidant enzyme,
      manganese superoxide dismutase (MnSOD), was encapsulated in huc-MSC-EVs and
      reduced oxidative stress in the hepatic IRI model. Knockdown of MnSOD in huc-MSCs
      decreased the level of MnSOD in huc-MSC-EVs and attenuated the anti-apoptosis and
      antioxidant capacities of huc-MSC-EVs, which could be partially rescued by MnSOD
      mimetic manganese (III) 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP).
      In summary, these findings provide new clues to reveal the therapeutic effects of
      huc-MSC-EVs on hepatic IRI and evaluate their preclinical application.-Yao, J.,
      Zheng, J., Cai, J., Zeng, K., Zhou, C., Zhang, J., Li, S., Li, H., Chen, L., He,
      L., Chen, H., Fu, H., Zhang, Q., Chen, G., Yang, Y., Zhang, Y. Extracellular
      vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat
      hepatic ischemia-reperfusion injury by suppressing oxidative stress and
      neutrophil inflammatory response.

PMID- 30226810
TI  - Experimental cerebral malaria is associated with profound loss of both glycan and
      protein components of the endothelial glycocalyx.
AB  - Vascular pathology is central to malaria pathogenesis and associated with
      severity of disease. We have previously documented shedding of the cerebral
      endothelial glycocalyx in experimental malaria and hypothesized that this action
      is implicated in the pathogenesis of cerebral malaria (CM). Quantification and
      characterization of the intraluminal vascular glycocalyx are technically
      challenging. Here, we used ferritin labeling, computerized image analysis, and
      biochemical characterization by using in vivo biotinylation and pull down. Image
      analysis divided mice with CM and uncomplicated malaria and uninfected control
      mice into 3 non-overlapping groups. Biochemical assessment of the luminal surface
      revealed malaria-induced alterations in all components of the glycocalyx in CM.
      This loss was mirrored in increases of the same components in peripheral blood
      samples. Corticosteroid treatment protected against CM, reduced inflammation, and
      prevented glycocalyx loss. Adjunctive antithrombin-3 also prevented glycocalyx
      loss and significantly reduced CM-associated mortality, as well as reduced local
      inflammation and prevented blood-brain barrier leakage. In contrast, inhibition
      of matrix metalloproteases with batimastat had limited effects on the glycocalyx
      and disease progression. Thus, glycocalyx loss may be associated with malaria
      pathogenesis and could be targeted by adjunctive treatment.-Hempel, C., Sporring,
      J., Kurtzhals, J. A. L. Experimental cerebral malaria is associated with profound
      loss of both glycan and protein components of the endothelial glycocalyx.

PMID- 30226811
TI  - Kinetics of corneal leukocytes by intravital multiphoton microscopy.
AB  - Corneal immune privilege is integral in maintaining the clear avascular window to
      the foreign world. The presence of distinct populations of corneal leukocytes
      (CLs) in the normal cornea has been firmly established. However, their precise
      function and kinetics remain, as of yet, unclear. Through intravital multiphoton
      microscopy (IV-MPM), allowing the means to accumulate critical spatial and
      temporal cellular information, we provide details for long-term investigation of
      CL morphology and kinetics under steady state and following inflammation.
      Significant alterations in size and morphology of corneal CD11c+ dendritic cells
      (DCs) were noted following acute sterile inflammation, including cell volume
      (4364.4 +/- 489.6 vs. 1787.6 +/- 111.0 MUm3, P < 0.001) and sphericity (0.82 +/-
      0.01 vs. 0.42 +/- 0.02, P < 0.001) compared with steady state. Furthermore, IV
      MPM analyses revealed alterations in both the CD11c+ DC and major
      histocompatibility complex class II (MHC)-II+ mature antigen-presenting cell
      population kinetics during inflammation, including track displacement length
      (CD11c: 16.57 +/- 1.41 vs. 4.64 +/- 0.56 MUm, P < 0.001; MHC-II: 9.03 +/- 0.37
      vs. 4.09 +/- 0.39, P < 0.001) and velocity (CD11c: 1.91 +/- 0.07 MUm/min vs. 1.73
      +/- 0.1302 MUm/min; MHC-II: 2.97 +/- 0.07 vs. 1.62 +/- 0.08, P < 0.001) compared
      with steady state. Our results reveal in vivo evidence of sessile CL populations
      exhibiting dendritic morphology under steady state and increased velocity of
      spherical leukocytes following inflammation. IV-MPM represents a powerful tool to
      study leukocytes in corneal diseases in context.-Seyed-Razavi, Y., Lopez, M. J.,
      Mantopoulos, D., Zheng, L., Massberg, S., Sendra, V. G., Harris, D. L., Hamrah,
      P. Kinetics of corneal leukocytes by intravital multiphoton microscopy.

PMID- 30226812
TI  - Insulin induces phosphorylation of pyruvate dehydrogenase through RhoA activation
      pathway in HepG2 cells.
AB  - Insulin is a critical signaling molecule in reducing blood glucose levels, and
      pyruvate dehydrogenase (PDH) is an essential enzyme in regulating glucose
      metabolism. However, the insulin effect on PDH function has not been well
      established. We observed that insulin attenuated the phosphorylation (p) of
      Ser264 (p-Ser264) in the PDH E1alpha subunit (PDHA1) in normal rat hepatocyte. In
      contrast, insulin induced an increase of p-Ser264 PDHA1 levels in hepatocellular
      carcinoma HepG2 and Huh7 cells. Insulin activated RhoA and Rho-dependent coiled
      coil kinase, an effector protein of active RhoA, which regulated p-Ser264 PDHA1
      levels, along with both p-Ser9 and p-Tyr216 forms of glycogen synthase kinase
      3beta (GSK-3beta) in HepG2 cells. Only p-Tyr216 GSK-3beta, the active form was
      involved in an increase of p-Ser264 PDHA1. Akt was also engaged in p-Ser9 of GSK
      3beta, but neither in p-Tyr216 of GSK-3beta nor p-Ser264 of PDHA1 upon insulin.
      Reconstituted dephospho-mimic forms PDHA1 S264A and GSK-3beta Y216F impaired, but
      wild-types PDHA1 and GSK-3beta and phospho-mimic forms PDHA1 S264D and GSK-3beta
      Y216E increased cell proliferation upon insulin through expression of c-Myc and
      cyclin D1. Therefore, we propose that insulin-mediated p-PDHA1 is involved in the
      regulation of HepG2 cell proliferation through RhoA signaling pathway.-Islam, R.,
      Kim, J.-G., Park, Y., Cho, J.-Y., Cap, K.-C., Kho, A.-R., Chung, W.-S., Suh, S.
      W., Park, J.-B. Insulin induces phosphorylation of pyruvate dehydrogenase through
      RhoA activation pathway in HepG2 cells.

PMID- 30226813
TI  - linc-SCRG1 accelerates liver fibrosis by decreasing RNA-binding protein
      tristetraprolin.
AB  - The biologic roles of long noncoding RNAs (lncRNAs) in liver fibrosis remained
      unknown. Through microarray analysis, linc-SCRG1 (a lncRNA with transcript length
      3118 bp) was found up-regulated 13.62-fold in human cirrhotic tissues.
      Quantitative PCR verified that linc-SCRG1 increased along with liver fibrosis
      progression in human tissues and in activated LX2 cells induced by TGF-beta1.
      Knock-down of linc-SCRG1 significantly reversed the effects of TGF-beta1 on LX2,
      including inhibiting activation, promoting apoptosis, reducing proliferation,
      lessening invasion, and down-regulating genes [fibrosis-related mRNA: alpha
      smooth muscle actin ( alpha-SMA), type Iota collagen, and B-cell lymphoma-2;
      invasion-related mRNA: matrix metallopeptidase-2 ( MMP-2), MMP-9, and MMP-13;
      inflammation-related mRNA: TNF-alpha, IL-6, and IL-10]. linc-SCRG1 had binding
      sites with tristetraprolin (TTP), a kind of RNA-binding protein, and specifically
      combined to TTP proteins. Overexpression of linc-SCRG1 would cause TTP mRNA
      unstably and proteins decreasing. TTP mRNA was proved having negative relevance
      with linc-SCRG1 and was gradually reduced during human liver fibrosis
      progression. Overexpressing TTP resulted in knock-down of lincSCRG1 and degraded
      downstream target genes ( MMP-2 and TNF-alpha) in activated LX2. Overexpressing
      TTP had the same effects as small interfering RNA-lincSCRG1 (si- lincSCRG1),
      whereas knock-down of TTP had reversal effects on si- lincSCRG1 in activated LX2.
      In summary, linc-SCRG1 reduced TTP and restricted its degradation of target genes
      TNF-alpha and MMP-2. Therefore, linc-SCRG1 had a repressing TTP-elicited
      inactivation effect on hepatic stellate cell (HSC) phenotypes. Inhibition of linc
      SCRG1 may be a novel therapeutic approach to inactivate HSCs and extenuate human
      liver fibrosis.-Wu, J.-C., Luo, S.-Z., Liu, T., Lu, L.-G., Xu, M.-Y. linc-SCRG1
      accelerates liver fibrosis by decreasing RNA-binding protein tristetraprolin.

PMID- 30226814
TI  - Pharmacokinetic Variability in Pediatrics and Intensive Care: Toward a
      Personalized Dosing Approach.
AB  - Providing a safe and efficacious drug therapy for large and often heterogeneous
      populations is a challenging objective in clinical drug development and routine
      clinical practice. It has been known for years that the optimum dose required for
      many therapeutic agents among individuals is quite variable. A wide
      interindividual pharmacokinetic variability was described in clinically relevant
      populations such as pediatrics and critically ill patients. The aim of this
      article was to present the main individual factors influencing variability in
      these two populations and their applications. Growth and development are two
      specific features of children that are not observed in adults. And critically ill
      patients have a much higher level of sickness severity that is associated with
      profound pathophysiological changes. These particular features could lead to
      difficulties to attain therapeutic targets. Nonlinear mixed effects modeling is a
      common approach to identify unexplained population variability. This approach is
      often applied to evaluate and optimize drug therapy in particular populations.
      Numerous studies have been conducted in these two specific populations to
      characterize pharmacokinetic parameters and to identify individual factors
      influencing variability. Size, age and organ function appeared to be the main
      factors influencing pharmacokinetics in pediatrics. Factors influencing
      pharmacokinetics in critically ill patients were mainly cardiovascular system,
      organ dysfunction and organ support. Dosage individualization seems to be a key
      issue to optimize drug treatment in these specific populations. Clinically
      utility and safety of a model-based personalized drug therapy has been
      demonstrated for vancomycin in pediatrics. Many programs were available to
      optimize drug regimens, especially for antibiotic drugs in critically ill
      patients. This innovative personalized dosing approach is a promising way to
      optimize drug therapy in clinically relevant populations, such as pediatrics and
      critically ill patients.

PMID- 30226815
TI  - Machine-learning-based automatic identification of fetal abdominal circumference
      from ultrasound images.
AB  - OBJECTIVE: Obstetricians mainly use ultrasound imaging for fetal biometric
      measurements. However, such measurements are cumbersome. Hence, there is urgent
      need for automatic biometric estimation. Automated analysis of ultrasound images
      is complicated owing to the patient-specific, operator-dependent, and machine
      specific characteristics of such images. APPROACH: This paper proposes a method
      for the automatic fetal biometry estimation from 2D ultrasound data through
      several processes consisting of a specially designed convolutional neural network
      (CNN) and U-Net for each process. These machine learning techniques take
      clinicians' decisions, anatomical structures, and the characteristics of
      ultrasound images into account. The proposed method is divided into three steps:
      initial abdominal circumference (AC) estimation, AC measurement, and plane
      acceptance checking. MAIN RESULTS: A CNN is used to classify ultrasound images
      (stomach bubble, amniotic fluid, and umbilical vein), and a Hough transform is
      used to obtain an initial estimate of the AC. These data are applied to other
      CNNs to estimate the spine position and bone regions. Then, the obtained
      information is used to determine the final AC. After determining the AC, a U-Net
      and a classification CNN are used to check whether the image is suitable for AC
      measurement. Finally, the efficacy of the proposed method is validated by
      clinical data. SIGNIFICANCE: Our method achieved a Dice similarity metric of
      [Formula: see text] for AC measurement and an accuracy of 87.10% for our
      acceptance check of the fetal abdominal standard plane.

PMID- 30226816
TI  - How We May Become Detached from Our Patients and What We Can Do If This Happens.
AB  - When clinicians provide clinical care or participate in ethics consultations,
      they may feel exceptionally painful emotions. When they do, they may distance
      themselves emotionally from patients and families. This distancing may harm these
      parties profoundly. It is therefore critical that clinicians avoid this
      distancing. In this piece, I present an approach that lies outside traditional
      practice that clinicians may use to try to avoid and even reverse this
      distancing, if and when they sense that this may be occurring. This approach may
      also benefit patients and families. It may increase their sense that their
      clinicians are working with them as allies to achieve their shared medical goals.

PMID- 30226817
TI  - Deathbed Confession: When a Dying Patient Confesses to Murder: Clinical, Ethical,
      and Legal Implications.
AB  - During an initial palliative care assessment, a dying man discloses that he had
      killed several people whilst a young man. The junior doctor, to whom he revealed
      his story, consulted with senior palliative care colleagues. It was agreed that
      legal advice would be sought on the issue of breaching the man's confidentiality.
      Two legal opinions conflicted with each other. A decision was made by the
      clinical team not to inform the police. In this article the junior doctor, the
      palliative medicine specialist, a medical ethicist, and a lawyer consider the
      case from their various perspectives.

PMID- 30226818
TI  - Ethical Challenges in Acute Evaluation of Suspected Psychogenic Stroke Mimics.
AB  - Tissue plasminogen activator (tPA) is administered to patients with suspected
      ischemic stroke to improve blood flow to the brain In rare cases, patients
      present with complaints of stroke symptoms that appear to be non-organic due to
      malingering, factitious disorder, or conversion disorder (psychogenic stroke
      mimics). Deciding whether or not to administer tPA to these patients can be
      challenging. The risk of hemorrhage after administration of tPA is low, but not
      zero. The ethical principles of beneficence and nonmaleficence need to be weighed
      carefully in these situations. We present two cases of patients with suspected
      psychogenic stroke mimics to illustrate the ethical challenges faced in
      identifying and managing psychogenic stroke mimics. Further research is needed to
      demonstrate effective treatment strategies for patients with acute stroke
      symptoms of psychogenic etiology.

PMID- 30226819
TI  - Positive HIV Test Results from Deceased Organ Donors: Should We Disclose to Next
      of Kin?
AB  - In the context of deceased organ donation, donors are routinely tested for HIV,
      to check for suitability for organ donation. This article examines whether a
      donor's HIV status should be disclosed to the donor's next of kin. On the one
      hand, confidentiality requires that sensitive information not be disclosed, and a
      duty to respect confidentiality may persist after death. On the other hand,
      breaching confidentiality may benefit third parties at risk of having been
      infected by the organ donor, as it may permit them to be tested for HIV and seek
      treatment in case of positive results. We conclude that the duty to warn third
      parties surpasses the duty to respect confidentiality. However, in order to
      minimize risks linked to the breach of confidentiality, information should be
      restrained to only concerned third parties, that is, those susceptible to having
      been infected by the donor.

PMID- 30226820
TI  - Posthumous HIV Disclosure and Relational Rupture.
AB  - In response to Anne L. Dalle Ave and David M. Shaw, we agree with their general
      argument but emphasize a moral risk of HIV disclosure in deceased donation cases:
      the risk of relational rupture. Because of the importance that close
      relationships have to our sense of self and our life plans, this kind of rupture
      can have long-ranging implications for surviving loved ones. Moreover, the now
      deceased individual cannot participate in any relational mending. Our analysis
      reveals the hefty moral costs that disclosure can bring, which should influence
      what information is given to would-be donors and how organ procurement
      coordinators approach these conversations.

PMID- 30226821
TI  - Plain Anabaptists and Healthcare Ethics.
AB  - Plain Anabaptists are a small but rapidly growing ethnoreligious society with
      significant concentrations of population in a number of regions in North America.
      Among the most widely known of the various groups of Plain Anabaptists are the
      Amish and the Old Order Mennonites. It is the purpose of this article to provide
      insight into the culture and values of the Plain Anabaptists so that those who
      may be called upon to address ethical conflict involving Plain Anabaptists can do
      so with appropriate knowledge and sensitivity. The discussion of the culture and
      values of the Plain Anabaptists will be organized as follows: first we will
      explore the implications of Plain Anabaptist culture and values for applying the
      ethical principles of respect for autonomy and beneficence/nonmaleficence.
      Second, a brief description of several elements of Plain Anabaptist culture will
      be discussed with attention to the potential they create for ethical conflict in
      the healthcare setting.

PMID- 30226822
TI  - Refusal of Vaccination: A Test to Balance Societal and Individual Interests.
AB  - While all states in the United States require certain vaccinations for school
      attendance, all but three allow for religious exemptions to receiving such
      vaccinations, and 18 allow for exemptions on the basis of other deeply held
      personal beliefs. The rights of parents to raise children as they see fit may
      conflict with the duty of the government and society to protect the welfare of
      children. In the U.S., these conflicts have not been settled in a uniform and
      consistent manner. We apply a test that provides a concrete and formal rubric to
      evaluate such conflicts. For some vaccinations, based on the individual medical
      characteristics of the disease and the risks of being unvaccinated, the test
      would suggest that permitting conscientious exemptions is ethical. However, for
      vaccinations protecting against other diseases that are more severe or easily
      transmitted, the test would suggest that the federal government may ethically
      impose laws that deny such exemptions.

PMID- 30226823
TI  - Nursing Ethics Huddles to Decrease Moral Distress among Nurses in the Intensive
      Care Unit.
AB  - BACKGROUND: Moral distress (MD) is an emotional and psychological response to
      morally challenging dilemmas. Moral distress is experienced frequently by nurses
      in the intensive care unit (ICU) and can result in emotional anguish, work
      dissatisfaction, poor patient outcomes, and high levels of nurse turnover.
      Opportunities to discuss ethically challenging situations may lessen MD and its
      associated sequela. OBJECTIVE: The purpose of this project was to develop,
      implement, and evaluate the impact of nursing ethics huddles on participants' MD,
      clinical ethics knowledge, work satisfaction, and patient care among ICU nurses.
      SAMPLE AND SETTING: The sample, 32 nurses from three ICU settings in an 800-bed
      tertiary academic medical center, participated in six nursing ethics huddles over
      a two-month period. METHODS: Alvita K. Nathaniel's Theory of Moral Reckoning
      guided development of the nursing ethics huddle process. The Moral Distress
      Thermometer was administered at three data points: baseline level of MD, and pre-
      and post-huddle to determine changes in the subjects' level of MD. Focused
      content analysis was used to analyze qualitative responses from questionnaires
      about the subjects' perception of the effect of the huddles on work satisfaction
      and patient care. Knowledge attainment was evaluated via open-ended short-answer
      questions. RESULTS: Overall, use of nurse-ethicist-led nursing ethics huddles was
      associated with improved quality of work life, patient care, and clinical ethics
      knowledge. The change in pre- and post-nursing ethics huddles MD scores was
      statistically significant.

PMID- 30226824
TI  - "I Would Do It All Over Again": Cherishing Time and the Absence of Regret in
      Continuing a Pregnancy after a Life-Limiting Diagnosis.
AB  - Parents, after learning of a life-limiting fetal condition (LLFC), experience
      emotional distress and must consider options that impact the remainder of the
      pregnancy, their future lives, and family members. For those who continue, little
      is known about their long-term presence or absence of regret about their choice,
      the reasons for this feeling, or its impact on their life. The aim of this
      research was to examine the concept of decision regret in parents who opted to
      continue a pregnancy affected by an LLFC. The contextual factors, conditions, and
      consequences surrounding the presence or absence of regret were analyzed. Data
      were retrieved from a cross-sectional study using the Quality of Perinatal
      Palliative Care and Parental Satisfaction Instrument. Participants were parents
      (N = 405) who experienced a life-limiting prenatal diagnosis and opted to
      continue their pregnancy. Secondary data analysis examined qualitative responses
      (121/402) to an item addressing regret. Dimensional analysis was used to examine
      data, identifying context, conditions, and consequences associated with the
      presence or absence of regret. Absence of regret was articulated in 97.5 percent
      of participants. Parents valued the baby as a part of their family and had
      opportunities to love, hold, meet, and cherish their child. Participants
      treasured the time together before and after the birth. Although emotionally
      difficult, parents articulated an empowering, transformative experience that
      lingers over time.

PMID- 30226825
TI  - The Mission of Safety Net Hospitals: Charity or Equity?
AB  - The traditional mission of safety net hospitals has been charity, providing the
      best healthcare for all individuals no matter their ability to pay. The focus has
      been on vulnerable populations that are low-income, uninsured, and other upstream
      circumstances that manifest downstream as poor health, poor health outcomes, and
      repeated high-cost interventions that fail to break cycles of perpetual health
      instability. Safety net hospitals are committed to serving their populations,
      even if only temporarily, through provision of subsidies and filling gaps that
      exist in patients' lives. These interventions do not lead to the elimination of
      gaps, hence cyclical health instability persists. It is a new day in healthcare
      and what it means for people to be well. The focus is on improving health
      outcomes by addressing root causes of health instability such as unstable
      housing, income, education, and access to affordable healthy foods. This gives us
      pause to reflect on the traditional mission of safety net hospitals and the
      impact of charity in isolation. Are safety net hospitals missing an opportunity
      to mitigate and eliminate perpetual health instability? Can they shift the
      paradigm of healthcare for vulnerable populations to alter their quality-of-life
      course? To move forward, safety net hospitals have to change their mind set and
      existing narratives about what is possible for vulnerable populations to achieve.
      These historic giants in healthcare have an opportunity to use their assets and
      employ a methodology of disruption and innovation to shift the mission of safety
      net healthcare from charity to equity.

PMID- 30226826
TI  - Scribes, Electronic Health Records, and the Expectation of Confidentiality.
AB  - Electronic health record (EHRs) have largely replaced obsolete paper medical
      charts. This replacement has produced an increased demand on physicians' time and
      has compromised efficiency. In an attempt to overcome this perceived obstacle to
      productivity, physicians turned to medical scribes to perform the work required
      by EHRs. In doing so, they have introduced an uninvited participant in the
      physician-patient relationship and compromised patients' confidentiality. Scribes
      may be a successful work around for physicians frustrated by EHRs, but patients'
      confidentiality should not be sacrificed in the process.

PMID- 30226827
TI  - Regularizing firing patterns of rat subthalamic neurons ameliorates parkinsonian
      motor deficits.
AB  - The subthalamic nucleus (STN) is an effective therapeutic target for deep brain
      stimulation (DBS) for Parkinson's disease (PD), and histamine levels are elevated
      in the basal ganglia in PD patients. However, the effect of endogenous
      histaminergic modulation on STN neuronal activities and the neuronal mechanism
      underlying STN-DBS are unknown. Here, we report that STN neuronal firing patterns
      are more crucial than firing rates for motor control. Histamine excited STN
      neurons, but paradoxically ameliorated parkinsonian motor deficits, which we
      attributed to regularizing firing patterns of STN neurons via the
      hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) channel
      coupled to the H2 receptor. Intriguingly, DBS increased histamine release in the
      STN and regularized STN neuronal firing patterns under parkinsonian conditions.
      HCN2 contributed to the DBS-induced regularization of neuronal firing patterns,
      suppression of excessive beta oscillations, and alleviation of motor deficits in
      PD. The results reveal an indispensable role for regularizing STN neuronal firing
      patterns in amelioration of parkinsonian motor dysfunction and a functional
      compensation for histamine in parkinsonian basal ganglia circuitry. The findings
      provide insights into mechanisms of STN-DBS as well as potential therapeutic
      targets and STN-DBS strategies for PD.

PMID- 30226828
TI  - betaIV-Spectrin regulates STAT3 targeting to tune cardiac response to pressure
      overload.
AB  - Heart failure (HF) remains a major source of morbidity and mortality in the US.
      The multifunctional Ca2+/calmodulin-dependent kinase II (CaMKII) has emerged as a
      critical regulator of cardiac hypertrophy and failure, although the mechanisms
      remain unclear. Previous studies have established that the cytoskeletal protein
      betaIV-spectrin coordinates local CaMKII signaling. Here, we sought to determine
      the role of a spectrin-CaMKII complex in maladaptive remodeling in HF. Chronic
      pressure overload (6 weeks of transaortic constriction [TAC]) induced a decrease
      in cardiac function in WT mice but not in animals expressing truncated betaIV
      spectrin lacking spectrin-CaMKII interaction (qv3J mice). Underlying the observed
      differences in function was an unexpected differential regulation of STAT3
      related genes in qv3J TAC hearts. In vitro experiments demonstrated that betaIV
      spectrin serves as a target for CaMKII phosphorylation, which regulates its
      stability. Cardiac-specific betaIV-spectrin-KO (betaIV-cKO) mice showed STAT3
      dysregulation, fibrosis, and decreased cardiac function at baseline, similar to
      what was observed with TAC in WT mice. STAT3 inhibition restored normal cardiac
      structure and function in betaIV-cKO and WT TAC hearts. Our studies identify a
      spectrin-based complex essential for regulation of the cardiac response to
      chronic pressure overload. We anticipate that strategies targeting the new
      spectrin-based "statosome" will be effective at suppressing maladaptive
      remodeling in response to chronic stress.

PMID- 30226829
TI  - CNS-resident classical DCs play a critical role in CNS autoimmune disease.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating
      disease of the central nervous system (CNS), induced by the adoptive transfer of
      myelin-reactive CD4+ T cells into naive syngeneic mice. It is widely used as a
      rodent model of multiple sclerosis (MS). The development of EAE lesions is
      initiated when transferred CD4+ T cells access the CNS and are reactivated by
      local antigen-presenting cells (APCs) bearing endogenous myelin peptide/MHC class
      II complexes. The identity of the CNS-resident, lesion-initiating APCs is widely
      debated. Here we demonstrate that classical dendritic cells (cDCs) normally
      reside in the meninges, brain, and spinal cord in the steady state. These cells
      are unique among candidate CNS APCs in their ability to stimulate naive, as well
      as effector, myelin-specific T cells to proliferate and produce proinflammatory
      cytokines directly ex vivo. cDCs expanded in the meninges and CNS parenchyma in
      association with disease progression. Selective depletion of cDCs led to a
      decrease in the number of myelin-primed donor T cells in the CNS and reduced the
      incidence of clinical EAE by half. Based on our findings, we propose that cDCs,
      and the factors that regulate them, be further investigated as potential
      therapeutic targets in MS.

PMID- 30226830
TI  - Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23
      autoantibodies.
AB  - Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis
      hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic
      calcification due to deficiency of or resistance to intact fibroblast growth
      factor 23 (iFGF23). Inactivating mutations in FGF23, N
      acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as
      causing HFTC/HHS. We present what we believe is the first identified case of
      autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition
      to the classical clinical and biochemical features of hyperphosphatemic tumoral
      calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23
      levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or
      FGF receptor 1 (FGFR1) were identified. He subsequently developed type 1 diabetes
      mellitus, which raised the possibility of an autoimmune cause for
      hyperphosphatemic tumoral calcinosis. Luciferase immunoprecipitation systems
      revealed markedly elevated FGF23 autoantibodies without detectable FGFR1 or
      Klotho autoantibodies. Using an in vitro FGF23 functional assay, we found that
      the FGF23 autoantibodies in the patient's plasma blocked downstream signaling via
      the MAPK/ERK signaling pathway in a dose-dependent manner. Thus, this report
      describes the first case, to our knowledge, of autoimmune hyperphosphatemic
      tumoral calcinosis with pathogenic autoantibodies targeting FGF23. Identification
      of this pathophysiology extends the etiologic spectrum of hyperphosphatemic
      tumoral calcinosis and suggests that immunomodulatory therapy may be an effective
      treatment.

PMID- 30226831
TI  - Chromatin regulator Asxl1 loss and Nf1 haploinsufficiency cooperate to accelerate
      myeloid malignancy.
AB  - ASXL1 is frequently mutated in myeloid malignancies and is known to co-occur with
      other gene mutations. However, the molecular mechanisms underlying the
      leukemogenesis associated with ASXL1 and cooperating mutations remain to be
      elucidated. Here, we report that Asxl1 loss cooperated with haploinsufficiency of
      Nf1, a negative regulator of the RAS signaling pathway, to accelerate the
      development of myeloid leukemia in mice. Loss of Asxl1 and Nf1 in hematopoietic
      stem and progenitor cells resulted in a gain-of-function transcriptional
      activation of multiple pathways such as MYC, NRAS, and BRD4 that are critical for
      leukemogenesis. The hyperactive MYC and BRD9 transcription programs were
      correlated with elevated H3K4 trimethylation at the promoter regions of genes
      involving these pathways. Furthermore, pharmacological inhibition of both the
      MAPK pathway and BET bromodomain prevented leukemia initiation and inhibited
      disease progression in Asxl1Delta/Delta Nf1Delta/Delta mice. Concomitant
      mutations of ASXL1 and RAS pathway genes were associated with aggressive
      progression of myeloid malignancies in patients. This study sheds light on the
      effect of cooperation between epigenetic alterations and signaling pathways on
      accelerating the progression of myeloid malignancies and provides a rational
      therapeutic strategy for the treatment of myeloid malignancies with ASXL1 and RAS
      pathway gene mutations.

PMID- 30226832
TI  - CRYSTALLINE RETINOPATHY AND RETINAL VASCULOPATHY IN CALCIFIC UREMIC
      ARTERIOLOPATHY (CALCIPHYLAXIS).
AB  - PURPOSE: To report the posterior segment and retinal vascular manifestations of
      calcific uremic arteriolopathy (calciphylaxis). Clinical findings are correlated
      with multimodal imaging results. METHODS: Observational case report. RESULTS: A
      65-year-old white woman on hemodialysis was referred for assessment of poor
      vision bilaterally. Clinical examination demonstrated a crystalline retinopathy
      with stigma of previous retinal arterial occlusion. Fluorescein angiography
      revealed delayed retinal arterial filling bilaterally, sheathing of vessels, and
      peripheral nonperfusion. The crystals were hyperautofluorescent. Spectral domain
      and enhanced depth imaging optical coherence tomography localized the crystals
      within the retina with a predilection for the retinal arterial vasculature. The
      choriocapillaris was not involved. Two years prior, the patient developed
      necrotic skin lesions which were biopsied and confirmed the diagnosis of
      calciphylaxis. CONCLUSION: Calcific uremic arteriolopathy is an extremely rare
      cause of thrombogenic microangiopathy in end-stage renal disease patients.
      Retinal arterial occlusion appears to be a rare but significant cause of visual
      loss in this disease and is likely to be consequent to crystalline deposition in
      the retinal vasculature.

PMID- 30226833
TI  - Vertebral Body Lipoma: An Unusual Pathology Treated With Kyphoplasty.
AB  - STUDY DESIGN: Case report. OBJECTIVE: This case report is unique since this is
      the first vertebral lipom case that was treated by kyphoplasty alone. SUMMARY OF
      BACKGROUND DATA: Vertebral lipoma is extremely rare and our search of the English
      literature has revealed 20 patients in 16 reports. METHODS: A 32-year-old female
      patient was admitted to our neurosurgery department with the chief complaint of
      low back pain that had lasted nearly 1 year. A lumbar MR suggested a hemangioma
      and the patient was operated on. RESULTS: On microscopic examination, the lesion
      was seen to have a widely infiltrating appearance of mature fat tissue between
      bone trabeculae diagnosis was intraosseous lipoma. CONCLUSION: We believe that
      the management should be surgical total removal of the lesion even in
      incidentally found cases in order to obtain histologic diagnosis and pain relief.
      LEVEL OF EVIDENCE: 5.

PMID- 30226835
TI  - Science in the fight to uphold the rights of children.
AB  - The United States is the only major nation to not yet have ratified the United
      Nations Convention on the Rights of the Child (UNCRC). Recently, there has been
      an erosion of the rights of children across America, Europe, and elsewhere, but
      through science, we may have an opportunity to counter some of this alarming
      trend. In the area of vaccines, the scientific community can raise its voice on
      the dangers that nonmedical exemptions and delays pose to children at risk for
      measles, influenza, and other childhood illnesses. Poverty places infants and
      children at high risk for illness and homelessness. Gun violence and gun-related
      accidents are killing on average four American children daily, and climate change
      is promoting global pediatric malnutrition. Increasing international, federal,
      and state support to seek innovative solutions to these and related issues is a
      moral imperative.

PMID- 30226834
TI  - Tetrahydropalmatine Prevents High-Fat Diet-Induced Hyperlipidemia in Golden
      Hamsters (Mesocricetus Auratus).
AB  - BACKGROUND Hyperlipidemia is a major cause of atherosclerotic cardiovascular
      disease. Tetrahydropalmatine (THP) can exhibit hepatoprotective, anti-arrhythmic,
      and anti-inflammatory activities. The mechanism of THP on the hyperlipidemia
      remains unknown; therefore, the present study explored the role of THP in
      hyperlipidemia. MATERIAL AND METHODS We established an animal model of
      hyperlipidemia by high-fat diet (HFD) feeding. Blood samples were obtained for
      determination of serum cholesterol (TC), triglyceride (TG), low-density
      lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c),
      pro-inflammatory cytokines, and CYP7A1 expression. Histology was performed and
      inflammation was detected in the liver using hematoxylin-eosin (HE) staining and
      enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA and protein
      levels of TLR4 and TRAF-6 were determined by quantitative real-time PCR (qPCR)
      and Western blot, respectively. RESULTS THP suppressed hepatic lipid accumulation
      and reduced serum levels of TC, TG, LDL-c, and HDL-c in HFD-fed golden hamsters.
      THP increased cholesterol 7 a-hydroxylase (CYP7A1) expression and prevented
      inflammation by the limited reduction in interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) expressions in serum and liver. THP slightly increased
      the ratio of the body/liver weight. THP inhibited the mRNA and protein levels of
      Toll-like receptor 4 (TLR4) and TNF-receptor associated factor-6 (TRAF-6).
      CONCLUSIONS These results suggest that THP attenuates hyperlipidemia by multiple
      effects, including hepatoprotective and anti-inflammatory effects. Moreover, THP
      also suppressed the expressions of TLR4 and TRAF-6 in golden hamsters.

PMID- 30226836
TI  - Robust spatial memory maps encoded by networks with transient connections.
AB  - The spiking activity of principal cells in mammalian hippocampus encodes an
      internalized neuronal representation of the ambient space-a cognitive map. Once
      learned, such a map enables the animal to navigate a given environment for a long
      period. However, the neuronal substrate that produces this map is transient: the
      synaptic connections in the hippocampus and in the downstream neuronal networks
      never cease to form and to deteriorate at a rapid rate. How can the brain
      maintain a robust, reliable representation of space using a network that
      constantly changes its architecture? We address this question using a
      computational framework that allows evaluating the effect produced by the
      decaying connections between simulated hippocampal neurons on the properties of
      the cognitive map. Using novel Algebraic Topology techniques, we demonstrate that
      emergence of stable cognitive maps produced by networks with transient
      architectures is a generic phenomenon. The model also points out that
      deterioration of the cognitive map caused by weakening or lost connections
      between neurons may be compensated by simulating the neuronal activity. Lastly,
      the model explicates the importance of the complementary learning systems for
      processing spatial information at different levels of spatiotemporal granularity.

PMID- 30226837
TI  - Large-scale investigation of the reasons why potentially important genes are
      ignored.
AB  - Biomedical research has been previously reported to primarily focus on a minority
      of all known genes. Here, we demonstrate that these differences in attention can
      be explained, to a large extent, exclusively from a small set of identifiable
      chemical, physical, and biological properties of genes. Together with knowledge
      about homologous genes from model organisms, these features allow us to
      accurately predict the number of publications on individual human genes, the year
      of their first report, the levels of funding awarded by the National Institutes
      of Health (NIH), and the development of drugs against disease-associated genes.
      By explicitly identifying the reasons for gene-specific bias and performing a
      meta-analysis of existing computational and experimental knowledge bases, we
      describe gene-specific strategies for the identification of important but
      hitherto ignored genes that can open novel directions for future investigation.

PMID- 30226838
TI  - Detecting archaic introgression using an unadmixed outgroup.
AB  - Human populations outside of Africa have experienced at least two bouts of
      introgression from archaic humans, from Neanderthals and Denisovans. In Papuans
      there is prior evidence of both these introgressions. Here we present a new
      approach to detect segments of individual genomes of archaic origin without using
      an archaic reference genome. The approach is based on a hidden Markov model that
      identifies genomic regions with a high density of single nucleotide variants
      (SNVs) not seen in unadmixed populations. We show using simulations that this
      provides a powerful approach to identifying segments of archaic introgression
      with a low rate of false detection, given data from a suitable outgroup
      population is available, without the archaic introgression but containing a
      majority of the variation that arose since initial separation from the archaic
      lineage. Furthermore our approach is able to infer admixture proportions and the
      times both of admixture and of initial divergence between the human and archaic
      populations. We apply the model to detect archaic introgression in 89 Papuans and
      show how the identified segments can be assigned to likely Neanderthal or
      Denisovan origin. We report more Denisovan admixture than previous studies and
      find a shift in size distribution of fragments of Neanderthal and Denisovan
      origin that is compatible with a difference in admixture time. Furthermore, we
      identify small amounts of Denisova ancestry in South East Asians and South
      Asians.

PMID- 30226840
TI  - All-atom normal mode dynamics of HIV-1 capsid.
AB  - Dynamics of biomolecular assemblies offer invaluable insights into their
      functional mechanisms. For extremely large biomolecular systems, such as HIV-1
      capsid that has nearly 5 millions atoms, obtaining its normal mode dynamics using
      even coarse-grained models can be a challenging task. In this work, we have
      successfully carried out a normal mode analysis of an entire HIV-1 capsid in full
      all-atom details. This is made possible through our newly developed BOSE (Block
      of Selected Elasticity) model that is founded on the principle of resonance
      discovered in our recent work. The resonance principle makes it possible to most
      efficiently compute the vibrations of a whole capsid at any given frequency by
      projecting the motions of component capsomeres into a narrow subspace. We have
      conducted also assessments of the quality of the BOSE modes by comparing them
      with benchmark modes obtained directly from the original Hessian matrix. Our all
      atom normal mode dynamics study of the HIV-1 capsid reveals the dynamic role of
      the pentamers in stabilizing the capsid structure and is in agreement with
      experimental findings that suggest capsid disassembly and uncoating start when
      the pentamers become destabilized. Our results on the dynamics of hexamer pores
      suggest that nucleotide transport should take place mostly at hexamers near
      pentamers, especially at the larger hemispherical end.

PMID- 30226839
TI  - Evolution of Endothelin signaling and diversification of adult pigment pattern in
      Danio fishes.
AB  - Fishes of the genus Danio exhibit diverse pigment patterns that serve as useful
      models for understanding the genes and cell behaviors underlying the evolution of
      adult form. Among these species, zebrafish D. rerio exhibit several dark stripes
      of melanophores with sparse iridophores that alternate with light interstripes of
      dense iridophores and xanthophores. By contrast, the closely related species D.
      nigrofasciatus has an attenuated pattern with fewer melanophores, stripes and
      interstripes. Here we demonstrate species differences in iridophore development
      that presage the fully formed patterns. Using genetic and transgenic approaches
      we identify the secreted peptide Endothelin-3 (Edn3)-a known melanogenic factor
      of tetrapods-as contributing to reduced iridophore proliferation and fewer
      stripes and interstripes in D. nigrofasciatus. We further show the locus encoding
      this factor is expressed at lower levels in D. nigrofasciatus owing to cis
      regulatory differences between species. Finally, we show that functions of two
      paralogous loci encoding Edn3 have been partitioned between skin and non-skin
      iridophores. Our findings reveal genetic and cellular mechanisms contributing to
      pattern differences between these species and suggest a model for evolutionary
      changes in Edn3 requirements for pigment patterning and its diversification
      across vertebrates.

PMID- 30226841
TI  - Detection of masses in mammograms using a one-stage object detector based on a
      deep convolutional neural network.
AB  - Several computer aided diagnosis (CAD) systems have been developed for
      mammography. They are widely used in certain countries such as the U.S. where
      mammography studies are conducted more frequently; however, they are not yet
      globally employed for clinical use due to their inconsistent performance, which
      can be attributed to their reliance on hand-crafted features. It is difficult to
      use hand-crafted features for mammogram images that vary due to factors such as
      the breast density of patients and differences in imaging devices. To address
      these problems, several studies have leveraged a deep convolutional neural
      network that does not require hand-crafted features. Among the recent object
      detectors, RetinaNet is particularly promising as it is a simpler one-stage
      object detector that is fast and efficient while achieving state-of-the-art
      performance. RetinaNet has been proven to perform conventional object detection
      tasks but has not been tested on detecting masses in mammograms. Thus, we propose
      a mass detection model based on RetinaNet. To validate its performance in diverse
      use cases, we construct several experimental setups using the public dataset
      INbreast and the in-house dataset GURO. In addition to training and testing on
      the same dataset (i.e., training and testing on INbreast), we evaluate our mass
      detection model in setups using additional training data (i.e., training on
      INbreast + GURO and testing on INbreast). We also evaluate our model in setups
      using pre-trained weights (i.e., using weights pre-trained on GURO, training and
      testing on INbreast). In all the experiments, our mass detection model achieves
      comparable or better performance than more complex state-of-the-art models
      including the two-stage object detector. Also, the results show that using the
      weights pre-trained on datasets achieves similar performance as directly using
      datasets in the training phase. Therefore, we make our mass detection model's
      weights pre-trained on both GURO and INbreast publicly available. We expect that
      researchers who train RetinaNet on their in-house dataset for the mass detection
      task can use our pre-trained weights to leverage the features extracted from the
      datasets.

PMID- 30226843
TI  - Substrate accumulation and extracellular matrix remodelling promote persistent
      upper airway disease in mucopolysaccharidosis patients on enzyme replacement
      therapy.
AB  - INTRODUCTION: Mucopolysaccharide diseases are a group of lysosomal storage
      disorders caused by deficiencies of hydrolase enzymes, leading to pathological
      glycosaminoglycan accumulation. A number of mucopolysaccharidosis (MPS) types are
      characterised by severe airway disease, the aetiology of which is poorly
      understood. There is ongoing evidence of significant clinical disease in the long
      term despite disease modifying therapeutic strategies, including enzyme
      replacement therapy (ERT). To provide a better understanding of this aspect of
      disease, we have characterised extracellular matrix (ECM) and inflammatory
      alterations in adenotonsillar tissue samples from 8 MPS patients. METHODS:
      Adenotonsillar samples from MPS I, IVA and VI ERT treated patients and from a
      single enzyme naive MPS IIIA individual were compared to non-affected control
      samples using quantitative immunohistochemistry, qPCR and biochemical analysis.
      RESULTS: Significantly increased lysosomal compartment size and total sulphated
      glycosaminoglycan (p = 0.0007, 0.02) were identified in patient samples despite
      ERT. Heparan sulphate glycosaminoglycan was significantly elevated in MPS I and
      IIIA (p = 0.002), confirming incomplete reversal of disease. Collagen IV and
      laminin alpha-5 (p = 0.002, 0.0004) staining demonstrated increased ECM
      deposition within the reticular and capillary network of MPS samples. No
      significant change in the expression of the pro-inflammatory cytokines IL-1alpha,
      IL-6 or TNF-alpha was seen compared to control. CONCLUSION: This study suggests a
      role for ECM remodelling contributing to the obstructive phenotype of airway
      disease in MPS. Current therapeutic strategies with ERT fail to normalise these
      pathological alterations within adenotonsillar samples. Our findings lend novel
      insight into the pathological cascade of events, with primarily structural rather
      than inflammatory changes contributing to the continuing phenotype seen in
      patients despite current therapeutic regimes.

PMID- 30226842
TI  - Nutritional quality of food as represented by the FSAm-NPS nutrient profiling
      system underlying the Nutri-Score label and cancer risk in Europe: Results from
      the EPIC prospective cohort study.
AB  - BACKGROUND: Helping consumers make healthier food choices is a key issue for the
      prevention of cancer and other diseases. In many countries, political authorities
      are considering the implementation of a simplified labelling system to reflect
      the nutritional quality of food products. The Nutri-Score, a five-colour
      nutrition label, is derived from the Nutrient Profiling System of the British
      Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods
      with high/low FSAm-NPS relates to cancer risk has been studied in
      national/regional cohorts but has not been characterized in diverse European
      populations. METHODS AND FINDINGS: This prospective analysis included 471,495
      adults from the European Prospective Investigation into Cancer and Nutrition
      (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794
      incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745;
      colon-rectum, n = 5,806). Usual food intakes were assessed with standardized
      country-specific diet assessment methods. The FSAm-NPS was calculated for each
      food/beverage using their 100-g content in energy, sugar, saturated fatty acid,
      sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores
      of all food items usually consumed by a participant were averaged to obtain the
      individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional
      hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower
      nutritional quality of the food consumed, was associated with a higher risk of
      total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute
      cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores
      were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI
      scores were specifically associated with higher risks of cancers of the colon
      rectum, upper aerodigestive tract and stomach, lung for men, and liver and
      postmenopausal breast for women (all P < 0.05). The main study limitation is that
      it was based on an observational cohort using self-reported dietary data obtained
      through a single baseline food frequency questionnaire; thus, exposure
      misclassification and residual confounding cannot be ruled out. CONCLUSIONS: In
      this large multinational European cohort, the consumption of food products with a
      higher FSAm-NPS score (lower nutritional quality) was associated with a higher
      risk of cancer. This supports the relevance of the FSAm-NPS as underlying
      nutrient profiling system for front-of-pack nutrition labels, as well as for
      other public health nutritional measures.

PMID- 30226844
TI  - Genetic diversity and biogeography of T. officinale inferred from multi locus
      sequence typing approach.
AB  - Taraxacum officinale (Asteraceae) is widely distributed weedy plant used as a
      traditional medicinal herb. The population genetics and historical biogeography
      of this plant have remained relatively unexplored. This study explores phylogeny,
      population genetics and ancestral reconstructions adopting multi locus sequence
      typing (MLST) approach. MLST sequences dataset was generated from genomics and
      chloroplast DNA sequences obtained from 31 T. officinale haplotypes located in 16
      different countries. Phylogenetic analysis distributed these haplotypes in well
      differentiated geographic clades. The study suggested a close relationship
      between Europe and adjacent Asian countries. Populations of these regions
      predominantly formed common haplogroups, showed considerable level of gene flow
      and evidence for recombination events across European and Asian population.
      Biogeographical inferences obtained by applying statistical dispersal-vicariance
      analysis (S-DIVA) and Bayesian binary MCMC (BBM) analysis showed that T.
      officinale was putatively originated in Europe. Molecular clock analysis based on
      ITS dataset suggested that the divergence between Europe and East Asian
      populations can be dated to 1.07 Mya with subsequent dispersal and vicariance
      events. Among different spatial process long distance seed dispersal mediated by
      wind had potentially assisted the population expansion of T. officinale.

PMID- 30226845
TI  - Biomarkers as predictors of sudden cardiac death in coronary artery disease
      patients with preserved left ventricular function (ARTEMIS study).
AB  - AIMS: Biomarkers have shown promising results in risk assessment of
      cardiovascular events. Their role in predicting the risk of sudden cardiac death
      (SCD) is not well established. We tested the performance of several biomarkers in
      risk assessment for SCD in patients with coronary artery disease (CAD) and
      preserved left ventricular function. METHODS AND RESULTS: The study population
      consisted of 1,946 CAD patients (68% male; mean age 66.9+/-8.6 yrs; type 2
      diabetes (T2D) 43%) enrolled in the ARTEMIS study. The study subjects underwent
      examinations with echocardiography and measurement of several biomarkers. The
      primary endpoint of the study was SCD. During the mean follow up of 76+/-20
      months 50 patients experienced SCD. Elevated high sensitive CRP (hs-CRP, p =
      0.001), soluble ST2 (sST2, p<0.001), B-type natriuretic peptide (BNP, p<0.001),
      and highly sensitive TroponinT (hs-TnT, p<0.001) predicted the occurrence of SCD
      in univariate analysis. Using the optimal cutoff points, elevated sST2
      (>=27.45ng/mL; hazard ratio [HR] 2.7; 95%CI 1.4-5.1, p = 0.003) and hs-TnT (>=15
      ng/mL; HR 2.9; 95% CI 1.5-5.6, p = 0.002) were the strongest predictors of SCD
      followed by hs-CRP (HR 2.4; 95% CI 1.3-4.4, p = 0.004) and BNP (HR 1.9; 95% CI
      1.0-3.7, p = 0.046) in adjusted analysis. Combination of elevated hs-TnT and sST2
      resulted in adjusted HR of 6.4 (95% CI 2.6-15.5, p<0.001). CONCLUSION: Elevated
      sST2 and hs-TnT predict the occurrence of SCD among patients with CAD and
      preserved left ventricular function. The association between sST2, hs-TnT and SCD
      may be explained by an ongoing myocardial apoptosis followed by fibrosis leading
      to vulnerability to malignant arrhythmias.

PMID- 30226846
TI  - Using dynamic Brownian Bridge Movement Models to identify home range size and
      movement patterns in king cobras.
AB  - Home range estimators are a critical component for understanding animal spatial
      ecology. The choice of home range estimator in spatial ecology studies can
      significantly influence management and conservation actions, as different methods
      lead to vastly different interpretations of movement patterns, habitat selection,
      as well as home range requirements. Reptile studies in particular have struggled
      to reach a consensus on the appropriate home range estimators to use, and species
      with cryptic behavior make home range assessment difficult. We applied dynamic
      Brownian Bridge Movement Models (dBBMMs) to radio-telemetry data from Ophiophagus
      hannah, a wide-ranging snake species. We used two focal individuals at different
      life stages (one juvenile male and one adult male) and sought to identify whether
      the method would accurately represent both their home range and movement
      patterns. To assess the suitability of dBBMMs, we compared this novel method with
      traditional home range estimation methods: minimum convex polygons (MCP) and
      Kernel density estimators (KDE). Both KDE and MCP incorporated higher levels of
      Type I and Type II errors, which would lead to biases in our understanding of
      this species space-use and habitat selection. Although these methods identified
      some general spatial-temporal patterns, dBBMMs were more efficient at detecting
      movement corridors and accurately representing long-term shelters sites, showing
      an improvement over methods traditionally favored in reptile studies. The
      additional flexibility of the dBBMM approach in providing insight into movement
      patterns can help further improve conservation and management actions.
      Additionally, our results suggest that dBBMMs may be more widely applicable in
      studies that rely on VHF telemetry and not limited to studies employing GPS tags.

PMID- 30226848
TI  - A measure of identifying influential waypoints in air route networks.
AB  - As the basic carrier of air flight operation, air route network (ARN) is of great
      significance to the smooth operation of flights. However, the waypoint is a core
      part of the route, so it is an important topic to identify influential waypoints
      in ARN. In this paper, a method to identify the influence of the node in ARN
      based on an improved entropy weight (IEW) method is proposed. Then, centrality
      measures including degree, closeness, betweenness and eigenvector as the multi
      attribute of ARN in IEW application. IEW method is used to aggregate the multi
      attribute to obtain the evaluation of the influence of each waypoint. To
      demonstrate the effectiveness of the IEW method, three real ARNs are selected to
      conduct several experiments with susceptible infected recovered (SIR) model. The
      results show the efficiency and practicability of the proposed method.

PMID- 30226847
TI  - The prevalence of brucellosis and bovine tuberculosis in ruminants in Sidi Kacem
      Province, Morocco.
AB  - Bovine tuberculosis (BTB) and brucellosis are major endemic zoonoses in ruminants
      in Morocco that impact on both animal and human health. This study presents an
      assessment of the epidemiological and socioeconomic burden of bacterial zoonoses
      in Sidi Kacem Province in Northern Morocco from a cross-sectional survey of 125
      cattle and/or small ruminant-owning households. In total, 1082 sheep and goats
      were examined from 81 households. The single intradermal comparative cervical
      test to screen for bovine tuberculosis was undertaken on 1194 cattle from 123
      households and all cattle were blood sampled. Cattle and small ruminant sera were
      tested for brucellosis using the standard Rose Bengal Test (sRBT) and the
      modified Rose Bengal Test (mRBT). Bacteriology was performed on 21 milk samples
      obtained from cattle that were seropositive for brucellosis for isolation and
      phenotyping of circulating Brucella strains. Individual and herd prevalence for
      BTB in cattle of 20.4% (95% CI 18%-23%) and 57.7% (95% CI 48%-66%), respectively,
      were observed in this study. The prevalence of brucellosis in cattle at
      individual and herd level was 1.9% (95% CI 1.2%-2.8%) and 9% (95% CI 4.5%-1.5%),
      respectively. Brucella pathogens were isolated from three cattle milk samples and
      were identified as B. abortus using Bruceladder(r) multiplex PCR and B. abortus
      biovar 1 by classical phenotyping. All small ruminants were seronegative to sRBT,
      two were positive to mRBT. A higher risk of BTB and brucellosis was observed in
      cattle in intensive livestock systems, in imported and crossed breeds and in
      animals from larger herds (>15). The three risk factors were usually present in
      the same herds, leading to higher transmission risk and persistence of both
      zoonoses. These results highlight the importance of implementing control
      strategies for both BTB and brucellosis to reduce productivity losses and the
      risk of transmission to humans. Prioritising control for BTB and brucellosis in
      intensive livestock production systems is essential for human and animal health.

PMID- 30226849
TI  - Detecting spatial clusters of HIV and hepatitis coinfections.
AB  - BACKGROUND: People with HIV infection in the United States are often affected by
      chronic viral hepatitis. These coinfected people with either HBV or HCV are at
      increased risk for serious, life-threatening complications. Coinfections with
      viral hepatitis may also complicate the delivery of anti-retroviral therapy (ART)
      by escalating the risk of drug-related hepatoxicity. According to the Centers for
      Disease Control and Prevention (CDC), approximately 10 percent of people with HIV
      in the United States also have HBV, and 25 percent also have HCV coinfection.
      With the advent of highly active antiretroviral therapy (HAART) and the increased
      life-expectancy of HIV patients, clinicians are more likely to be confronted with
      issues related to co-infection and the management challenges that they present,
      especially in resource-limited settings. The purpose of this analysis was to
      identify geographical clusters of HIV- (HBV/HCV) co-infection and compared to the
      geographical clusters of not co-infected using DC, Department of Health
      surveillance data. The results of the analysis will be used to target resources
      to areas at risk. METHODS: HIV and Hepatitis surveillance data were matched among
      cases diagnosed between 1980 and 2016. HIV-hepatitis co-infected and the not co
      infected spatial clusters were detected using discrete Poisson model. Kulldorff's
      spatial scan statistic method was implemented in the free software tool called
      SaTScan which has been widely adopted for detecting disease cluster. The analysis
      was conducted by tracts, but for visualization, ease of interpretation and assist
      in policy making the tract map was overlaid with the ward map using ArcGIS
      10.5.1. RESULTS: Between 1980 and 2016, there were 12,965 diagnosed cases of HIV,
      of which 2,316 HIV/Hepatitis matches were identified. Of the 2316 co-infected
      people living in DC, 25 percent (N = 590) of people had HBV, and 75 percent (N =
      1,726) had HCV. Out of 12,965 diagnosed cases, remaining 10,649 did not have any
      co-infections (not co-infected). IDU (27.16 percent) and MSM (32.86 percent) were
      the highest mode of transmission for co-infected population. African-American
      were reported 83.64 percent (N = 1,937) among co-infection population. Three
      clusters were identified for both co-infected population in DC. The largest
      cluster radius for co-infected analysis covers wards 6, 7 and 8 as well as large
      parts of 2 and 5 (p < 0.001). Multiple clusters were identified for not co
      infected population (p < 0.001). IDU (n = 450) was the highest mode of
      transmission for the co-infected clusters. For all clusters combined of not co
      infected population highest mode of transmission were MSM (n = 2,534). This
      analysis also showed racial disparity, economic deprivation and lack of education
      were prominent in the co-infected clusters. CONCLUSION: We identified locations
      of high risk clusters where enhanced hepatitis and HIV prevention, treatment, and
      care can help combat the epidemic. The clusters radius expands into the
      neighboring state of Maryland as well. The findings from this analysis will be
      used to target area based public health policy and healthcare interventions for
      HIV-hepatitis. It is recommended based on the analysis that needle exchange
      programs can successfully control new HIV infections as well as hepatitis co
      infections.

PMID- 30226850
TI  - Mortality in nursing home residents: A longitudinal study over three years.
AB  - OBJECTIVE: Nursing home (NH) stay is the highest level of formal care. With the
      expected demographic changes ahead, the need for NH placement will put an
      increasing socioeconomic strain on the society. Survival in NHs and factors
      predicting survival are important knowledge in order to evaluate NH admission
      policies and plan future NH capacity. METHODS: We followed 690 NH residents
      included at admission to NH over a period of three years. Participants were
      examined at baseline (BL) and every six months. Demographic and clinical data
      were collected, including comorbidity, severity of cognitive impairment,
      dependency in activities of daily living (ADL) and neuropsychiatric symptoms.
      Median survival was calculated by the Kaplan-Meier analysis, and factors
      associated with mortality were identified by Cox models with baseline and time
      dependent covariates. RESULTS: Median survival in NH was 2.2 years (95%
      confidence interval [CI]: 1.9-2.4). Yearly mortality rate throughout the three
      year observation period was 31.8%. Mortality was associated with higher age and
      comorbidity at BL, and more severe dementia, higher ADL-dependency, less severe
      psychotic symptoms, and a lower BMI throughout the study period. Of the
      organizational variables, living on a ward with more residents resulted in a
      higher risk of mortality. CONCLUSION: In conclusion, the NH mortality rate
      remained stable throughout the three-year study period with about one third of
      the residents deceasing each year. Individual resident characteristics appeared
      to be more important than organizational variables for predicting mortality risk.
      The finding of an association between ward size and mortality risk deserves
      further investigation in future studies.

PMID- 30226851
TI  - Investigating potential mediator between statin and coronary artery
      calcification.
AB  - Statins are mainstay anti-lipidaemic treatments for preventing cardiovascular
      diseases but also known to increase coronary artery calcification (CAC). However,
      underlying relationship between statin and CAC is still unclear. This study
      explored the mediating role of five statin-related biochemical factors [i.e., low
      density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)
      cholesterol, triglyceride, glucose, and high sensitivity C-reactive protein
      levels]. Seoul Metabolic Syndrome cohort study includes 1370 participants
      suspected of metabolic syndrome. For causal mediation analysis, the dataset for
      2016 including 847 participants with coronary computed tomography without any
      missing value were analysed using the Mediation package in R software. This study
      identified a causal mediation mechanism of HDL-cholesterol among the five
      biochemical factors. It implied that statin treatment increases the HDL
      cholesterol level, leading to decreasing the probability of CAC score > 0.
      Estimated values of interest in HDL-cholesterol mediation were (1) average causal
      mediation effect, -0.011 with 95% CI [-0.025, -0.003], (2) average direct effect,
      0.143 with 95% CI [0.074, 0.219], and total effect, 0.132 with 95% CI [0.063,
      0.209]. Its mediation effect was maintained regardless of statin intensity.
      Sensitivity analysis also provided a robustness of the results under potential
      existence of a confounder between HDL-cholesterol and CAC. This study suggests a
      potential causal pathway between statin and CAC (the positive association of
      statin on CAC) through HDL-cholesterol as an inhibitor.

PMID- 30226852
TI  - Inequality in total fertility rates and the proximate determinants of fertility
      in 21 sub-Saharan African countries.
AB  - In this paper, we examine the inequality in the dynamics of the total fertility
      rate within 21 sub-Saharan African countries by wealth quintiles. We also examine
      the associated inequality within each country in the proximate determinants of
      fertility-marriage, contraception, and breastfeeding. Applying Bongaarts'
      proximate determinants of fertility framework, for 14/21 countries we analyze, we
      find that those in the richest wealth quintiles have had a more rapid decline in
      fertility rates than those in the poorest wealth quintiles. The rapid decline for
      those in the richest wealth quintiles is attributable to delayed marriage and
      modest increases in contraceptive use. Although the poorest lag in fertility
      decline, postpartum abstinence and breastfeeding are the most important factors
      for them for fertility regulation. Further encouraging maternal health programs
      that focus on natural methods of fertility regulation will work in favor of the
      poorest in sub-Saharan Africa in moving through the demographic transition.

PMID- 30226853
TI  - Seasonality effects on chemical composition, antibacterial activity and essential
      oil yield of three species of Nectandra.
AB  - In this study, we aimed to determine whether seasonality affects the content,
      chemical composition, and antimicrobial activity of essential oils (EOs) from the
      leaves of three species of Nectandra (Nectandra megapotamica, Nectandra
      grandiflora, and Nectandra lanceolata) native to the Atlantic rainforest, Sao
      Paulo state, Brazil. In addition, we identified the compounds potentially related
      to the antimicrobial activity. Leaves were randomly collected in the middle of
      winter (August), spring (November), summer (February), and autumn (May). The
      influence of seasonality on the content and chemical composition of EOs from the
      Nectandra species was evident in this study. The EOs from N. lanceolata and N.
      grandiflora were characterized by similarities in the chemical composition and
      had a higher relative proportion of oxygenated sesquiterpenes. N. megapotamica
      presented a different chemical profile, with plenty of monoterpenic and
      sesquiterpenic hydrocarbons. Changes in the EO chemical profile because of
      seasonality were shown by the similarities between the EOs obtained in spring and
      autumn and the differences between the EOs obtained in summer and winter. The EO
      from the leaves of N. megapotamica harvested in winter and spring showed the
      highest control of the growth of Escherichia coli, and this antimicrobial action
      can be related to the monoterpenes alpha-pinene and beta-pinene as well as
      myrcene and limonene. The minimum inhibitory concentration (MIC) of the EO from
      the leaves of N. lanceolata harvested in summer and autumn was lower against the
      gram-positive bacterium Staphylococcus aureus and can be related to the
      sesquiterpene hydrocarbons isobicyclogermacrenal, epi-zizanone, and germacrene B.

PMID- 30226854
TI  - Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell
      responsiveness.
AB  - Cell response to extracellular ligand is affected not only by ligand
      availability, but also by pre-existing cell-to-cell variability that enables a
      range of responses within a cell population. We developed a computational model
      that incorporates cell heterogeneity in order to investigate Jurkat T cell
      response to time dependent extracellular IL-2 stimulation. Our model predicted
      preferred timing of IL-2 oscillatory input for maximizing downstream
      intracellular STAT5 nuclear translocation. The modeled cytokine exposure was
      replicated experimentally through the use of a microfluidic platform that enabled
      the parallelized capture of dynamic single cell response to precisely delivered
      pulses of IL-2 stimulus. The in vitro results demonstrate that single cell
      response profiles vary with pulsatile IL-2 input at pre-equilibrium levels. These
      observations confirmed our model predictions that Jurkat cells have a preferred
      range of extracellular IL-2 fluctuations, in which downstream response is rapidly
      initiated. Further investigation into this filtering behavior could increase our
      understanding of how pre-existing cellular states within immune cell populations
      enable a systems response within a preferred range of ligand fluctuations, and
      whether the observed cytokine range corresponds to in vivo conditions.

PMID- 30226855
TI  - EPIGIST: An observational real-life study on patients with metastatic
      gastrointestinal stromal tumors receiving imatinib.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare, but represent the
      most common mesenchymal neoplasms of the gastrointestinal tract. EPIdemiology
      GIST, is an observational multicenter longitudinal follow-up cohort study
      reporting the prescribing patterns of imatinib in patients with GIST and the
      impact of the treatment in a real-world (standard clinical) setting. METHODS:
      Eligible patients had a confirmed diagnosis of unresectable or metastatic KIT
      positive GIST and started treatment with imatinib for the first time between May
      24, 2002, and June 30, 2010. During routine visits, annual collection of clinical
      characteristics was requested, i.e., age, GIST stage at diagnosis, history,
      imatinib treatment duration and dosage, adherence, and concomitant medications.
      Survival outcomes were estimated using the Kaplan-Meier method. Other data were
      analyzed using descriptive statistics. RESULTS: Of 151 patients enrolled,
      imatinib was initiated for 126 patients before enrollment and for 25 patients on
      the day of enrollment or soon after. The patient characteristics were similar to
      those in published prospective trials. The estimated 1-, 2-, 3-, and 4-year
      overall survival rates were 90.4% (95% confidence interval [CI; 84.8%-94.0%]),
      84.7% (95% CI [78.1%-89.4%]), 73.0% (95% CI [65.0%-79.4%]), and 60.7% (95% CI
      [51.4%-68.8%]), respectively. The most common adverse events (AEs) were diarrhea
      (39%), asthenia (39%), eyelid or periorbital edema (32%), abdominal pain (23%),
      and anemia (21%). Eight of 126 serious AEs were possibly related to the treatment
      as assessed by investigators. CONCLUSIONS: Study results showed that patients in
      real-life populations are generally treated in accordance with national and
      international clinical recommendations and have outcomes comparable to those of
      patients in clinical trials.

PMID- 30226856
TI  - ACE gene haplotypes and social networks: Using a biocultural framework to
      investigate blood pressure variation in African Americans.
AB  - Deaths due to hypertension in the US are highest among African Americans, who
      have a higher prevalence of hypertension and more severe hypertensive symptoms.
      Research indicates that there are both genetic and sociocultural risk factors for
      hypertension. Racial disparities in hypertension also likely involve genetic and
      sociocultural factors, but the factors may interact and manifest differently
      across racial groups. Here we use a biocultural approach to integrate genetic and
      social network data to better understand variation in blood pressure. We assay
      genetic variation at the angiotensin I converting enzyme gene (ACE) and analyze
      social network composition and structure in African Americans living in
      Tallahassee, FL (n = 138). We demonstrate that models including both genetic and
      social network data explain significantly more variation in blood pressure and
      have better model diagnostics than do models including only one datatype.
      Specifically, optimal models for systolic and diastolic blood pressure explain a
      notable 35% and 21%, respectively, of blood pressure variation. Analysis of the
      social networks reveals that individuals whose networks are dominated by family
      connections and are more fragmented have higher blood pressure. Historically,
      family support has been associated with better mental and physical health, but
      our results suggest that those family connections can also take a toll on health.
      These findings raise compelling questions regarding the roles of genetics,
      family, and social environment in hypertension in the African American community
      and suggest that interactions among these factors may help explain racial
      disparities in hypertension more accurately than any of the factors alone.

PMID- 30226857
TI  - The complete plastid genomes of Ophrys iricolor and O. sphegodes (Orchidaceae)
      and comparative analyses with other orchids.
AB  - Sexually deceptive orchids of the genus Ophrys may rapidly evolve by adaptation
      to pollinators. However, understanding of the genetic basis of potential changes
      and patterns of relationships is hampered by a lack of genomic information. We
      report the complete plastid genome sequences of Ophrys iricolor and O. sphegodes,
      representing the two most species-rich lineages of the genus Ophrys. Both
      plastomes are circular DNA molecules (146754 bp for O. sphegodes and 150177 bp
      for O. iricolor) with the typical quadripartite structure of plastid genomes and
      within the average size of photosynthetic orchids. 213 Simple Sequence Repeats
      (SSRs) (31.5% polymorphic between O. iricolor and O. sphegodes) were identified,
      with homopolymers and dipolymers as the most common repeat types. SSRs were
      mainly located in intergenic regions but SSRs located in coding regions were also
      found, mainly in ycf1 and rpoC2 genes. The Ophrys plastome is predicted to encode
      107 distinct genes, 17 of which are completely duplicated in the Inverted Repeat
      regions. 83 and 87 putative RNA editing sites were detected in 25 plastid genes
      of the two Ophrys species, all occurring in the first or second codon position.
      Comparing the rate of nonsynonymous (dN) and synonymous (dS) substitutions, 24
      genes (including rbcL and ycf1) display signature consistent with positive
      selection. When compared with other members of the orchid family, the Ophrys
      plastome has a complete set of 11 functional ndh plastid genes, with the
      exception of O. sphegodes that has a truncated ndhF gene. Comparative analysis
      showed a large co-linearity with other related Orchidinae. However, in contrast
      to O. iricolor and other Orchidinae, O. sphegodes has a shift of the junction
      between the Inverted Repeat and Small Single Copy regions associated with the
      loss of the partial duplicated gene ycf1 and the truncation of the ndhF gene.
      Data on relative genomic coverage and validation by PCR indicate the presence,
      with a different ratio, of the two plastome types (i.e. with and without ndhF
      deletion) in both Ophrys species, with a predominance of the deleted type in O.
      sphegodes. A search for this deleted plastid region in O. sphegodes nuclear
      genome shows that the deleted region is inserted in a retrotransposon nuclear
      sequence. The present study provides useful genomic tools for studying
      conservation and patterns of relationships of this rapidly radiating orchid
      genus.

PMID- 30226858
TI  - Novel urinary exosomal biomarkers of acute T cell-mediated rejection in kidney
      transplant recipients: A cross-sectional study.
AB  - BACKGROUND: Acute rejection is hazardous to graft survival in kidney transplant
      recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of
      acute T cell-mediated rejection (TCMR) in urinary exosomes of KTRs. METHODS:
      Among 458 graft biopsies enrolled in a cross-sectional multicenter study, 22
      patients with stable graft function (STA) who had not shown pathologic
      abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We
      performed proteomic analysis using nano-ultra performance liquid chromatography
      tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for
      early TCMR diagnosis on urinary exosomes. We confirmed the protein levels of each
      candidate biomarker by western blot analysis. RESULTS: A total of 169 urinary
      exosome proteins were identified by nano-UPLC-MS/MS. Forty-six proteins showed
      increased expression in STA patients, while 17 proteins were increased in TCMR
      patients. Among them, we selected five proteins as candidate biomarkers for early
      diagnosis of TCMR according to significance, degree of quantity variance, and
      information from the ExoCarta database. We confirmed the proteomic expression
      levels of five candidate biomarkers by western blot analysis in each patient. Of
      all candidate biomarkers, tetraspanin-1 and hemopexin were significantly higher
      in TCMR patients (STA:TCMR ratio = 1:1.8, P = 0.009, and 1:3.5, P = 0.046,
      respectively). CONCLUSIONS: Tetraspanin-1 and hemopexin were detected in KTR
      urine and could act as potential diagnostic proteins for TCMR.

PMID- 30226859
TI  - ATRX loss induces multiple hallmarks of the alternative lengthening of telomeres
      (ALT) phenotype in human glioma cell lines in a cell line-specific manner.
AB  - Cancers must maintain their telomeres at lengths sufficient for cell survival. In
      several cancer subtypes, a recombination-like mechanism termed alternative
      lengthening of telomeres (ALT), is frequently used for telomere length
      maintenance. Cancers utilizing ALT often have lost functional ATRX, a chromatin
      remodeling protein, through mutation or deletion, thereby strongly implicating
      ATRX as an ALT suppressor. Herein, we have generated functional ATRX knockouts in
      four telomerase-positive, ALT-negative human glioma cell lines: MOG-G-UVW, SF188,
      U-251 and UW479. After loss of ATRX, two of the four cell lines (U-251 and UW479)
      show multiple characteristics of ALT-positive cells, including ultrabright
      telomeric DNA foci, ALT-associated PML bodies, and c-circles. However, telomerase
      activity and overall telomere length heterogeneity are unaffected after ATRX
      loss, regardless of cellular context. The two cell lines that showed ALT
      hallmarks after complete ATRX loss also did so upon ATRX depletion via shRNA
      mediated knockdown. These results suggest that other genomic or epigenetic
      events, in addition to ATRX loss, are necessary for the induction of ALT in human
      cancer.

PMID- 30226860
TI  - Sex-specific dmrt1 and cyp19a1 methylation and alternative splicing in gonads of
      the protandrous hermaphrodite barramundi.
AB  - Epigenetics is involved in sex differentiation of gonochoristic and
      hermaphroditic fish species, whereby two genes dmrt1 (pro-male) and cyp19a1 (pro
      female) are known to play major roles. Barramundi, Lates calcarifer, is an
      important tropical aquaculture species that undergo natural and permanent male to
      female sex change, a process for which the exact underlying molecular mechanisms
      are still unknown. To elucidate whether DNA methylation is involved in sex
      control of barramundi, a next-generation bisulfite amplicon sequencing approach
      was used to target 146 CpG sites within proximal promoters and first exons of
      seven sex-related genes (dmrt1, cyp19a1, amh, foxl2, nr5a2, sox8 and sox9) of 24
      testis and 18 ovaries of captive and wild adult barramundi. Moreover, comparative
      expression profiles of the key dmrt1 and cyp19a1 genes were further investigated
      using RT-qPCR and Sanger sequencing approaches, whereas expression levels of
      remaining targeted genes were based on available literature for the species.
      Results showed that cyp19a1 and amh were more methylated in males, whereas dmrt1
      and nr5a2 were more methylated in females (P < 0.001), with no gender differences
      found for foxl2, sox8 or sox9 genes (P > 0.05). Sex-biased promoter DNA
      methylation was inversely related to gene expression only for dmrt1 and nr5a2,
      and directly related to amh expression, whereas no differences in cyp19a1
      expression were found between testes and ovaries. Notably, unique sex-specific
      alternative splicing of dmrt1 and cyp19a1 were discovered, whereby males lacked
      the full-length aromatase coding cyp19a1 mRNA due to partial or total exon
      splicing, and females lacked the dmrt1 exon containing the DM-domain sequence.
      This study advances the current knowledge aiming to elucidate the genetic
      mechanisms within male and female gonads of this large protandrous hermaphrodite
      by providing the first evidence of epigenetics and alternative splicing
      simultaneously affecting key genes (cyp19a1 and dmrt1) central to sex
      differentiation pathways.

PMID- 30226861
TI  - Prognostic value of canine pancreatic lipase immunoreactivity and lipase activity
      in dogs with gastric dilatation-volvulus.
AB  - This study evaluated the association between a selection of candidate predictor
      variables, including the elevation of specific pancreatic enzymes, and outcome in
      dogs with gastric dilatation-volvulus (GDV). Twenty-two dogs with gastric
      dilatation-volvulus were included, being classified as survivors or non-survivors
      based on the final outcome. Dogs with intestinal obstruction (n = 16) were
      selected for comparison. Blood samples were collected upon admission (T0) and
      after 24 hours (T1). Serum lipase activity, canine pancreatic lipase
      immunoreactivity (cPLI) and other variables (plasma lactate concentration and C-
      reactive protein -CRP- in particular) were evaluated as predictive variables. T0
      cPLI and serum lipase activity were not found to differ significantly between
      dogs with gastric dilatation-volvulus or intestinal obstruction. Canine
      pancreatic lipase immunoreactivity values above 400 MUg/L were detected in 6/22
      dogs with gastric dilatation-volvulus and 4/16 with intestinal obstruction.
      However, lactate concentration was significantly higher and CRP significantly
      lower in GDV as compared to IO dogs, and in the GDV group, lipase, cPLI and CRP
      measured upon admission were significantly associated with a negative outcome. No
      differences in lipase activity and canine pancreatic lipase immunoreactivity
      values were detected between T0 and T1. Presurgical cPLI and lipase activity were
      frequently increased during gastric dilatation-volvulus and were suggestive of
      the presence of pancreatic damage; while more extensive studies are required,
      based on this pilot analysis, cPLI has the potential to be a useful predictive
      variable for outcome in GDV. Further to this, serum CRP was able to predict
      outcome in this population of dogs with GDV, while blood lactate was not.

PMID- 30226862
TI  - Experiences from a multimodal rhythm and music-based rehabilitation program in
      late phase of stroke recovery - A qualitative study.
AB  - BACKGROUND: Rehabilitative stroke interventions based on principles of multimodal
      stimulation have the potential to profoundly affect neuroplastic processes beyond
      the sub-acute phase. In order to identify important core mechanisms, there is a
      need to explore how interventions that combine physical, social, sensory, and
      cognitively challenging activities are perceived and experienced by the
      participants. This qualitative study, based on an interpretive interactionist
      perspective, explored the experiences of stroke survivors who participated in a
      group-based multimodal rehabilitation program based on rhythm and music. METHODS
      AND FINDINGS: Within four weeks after completion of the multimodal rehabilitation
      program, face-to-face semi-structured interviews were conducted on a single
      occasion with 15 purposively selected individuals (mean age 65, 8 men, 7 women).
      The interview duration was between 13 and 44 minutes. Qualitative content
      analysis with an inductive approach was used to analyze data. Three categories
      were identified, each containing several sub-categories: To be intellectually
      challenged (energy-consuming activity and coordinating multiple input and
      output), Perceived therapeutic benefits (motor skills, cognitive skills,
      emotional and psychological responses), and Pros and cons with social integration
      (fellowship, competing with others, and instructor characteristics). From these
      categories, an overall theme was derived: The multifaceted layers of multimodal
      stimulation. Enjoying music, being part of a group with peers, a skilled
      instructor, and being able to manage the challenging movements, were related to
      positive experiences. In contrast, negative experiences were associated with not
      being able to perform the exercises, and with group members who dominated the
      conversational space. CONCLUSION: This study shows that access to a multimodal
      rehabilitation program with rhythm and music as operating ingredients may
      contribute to positive experiences for many individuals in a late phase after
      stroke in terms of motor, cognitive, as well as emotional enhancements. Important
      components were the music, the social interaction, the challenging exercises, and
      the skilled instructor.

PMID- 30226863
TI  - Proprietary management and higher readmission rates: A correlation.
AB  - INTRODUCTION: Reducing preventable readmissions among Medicare beneficiaries is
      an effective way to not only reduce the exorbitantly rising cost in healthcare
      but also as a measure to improve the quality of patient care. Many of the
      previous efforts in reducing readmission rate of patients have not been very
      successful because of ill-defined quality measures, improper data collection
      methods and lack of effective strategies based on data driven solutions. METHODS:
      In this study, we analyzed the readmission data of patients for six major
      diseases including acute myocardial infarction (AMI), heart failure (HF),
      coronary artery bypass graft (CABG), pneumonia (PN), chronic obstructive
      pulmonary disease (COPD), and total hip arthroplasty and/or total knee
      arthroplasty (THA/TKA) from the Center for Medicare and Medicaid Readmissions
      Reduction Program (HRRP) program for the period 2012-2015 in context with the
      ownership structure of the hospitals. RESULTS: Our analysis demonstrates that the
      readmission rates of patients were statistically higher in proprietary (for
      profit) hospitals compared to the government and non-profit hospitals which was
      independent of their geographical distribution across all six major diseases.
      CONCLUSION: This finding we believe has strong implications for policy makers to
      mitigate any potential risks in the quality of patient care arising from
      unintended revenue pressure in healthcare institutions.

PMID- 30226864
TI  - Calving duration and obstetric assistance influence pulmonary function of
      Holstein calves during immediate fetal-to-neonatal transition.
AB  - Neonatal immediate adaptation to extrauterine life depends mainly on adequate
      lung function, which is under the influence of previous fetal maturation and
      obstetrical condition, both acting to stimulate the efficient liquid removal from
      the pulmonary parenchyma during the immediate transition period. The objective of
      the present study is to identify chest radiographic changes of neonatal calves
      born under the influence of different duration of calving and obstetric
      assistance and correlate with clinical analysis and blood acid-base balance.
      Experimental groups were determined according to the duration of calving: 2 h (n 
      =  16), 2-4 h (n  =  16) and >4 h (n  =  12), and additionally by two sub-groups:
      no-intervention calving (n  =  22) and intervention calving (n  =  22). Neonatal
      calves were evaluated for heart and respiratory rate at birth, 5 min, every 10
      min until 90 min. Arterial acid-base balance was determined immediately after
      calving and thoracic radiographs were made at 10 min of life. Lung radiopacity
      was higher in the 2-4 hr Group compared to the 2 hr Group. When calving duration
      was greater than 4 hours, a significant respiratory depression was observed.
      Calving greater than 2 hours slower neonatal pulmonary clearance, 100% and 91.6%
      of the calves born in the 2-4 hr and >4 hr Groups, respectively, had mild to
      moderate lung parenchyma opacity. There was a positive correlation between lung
      radiographic changes and blood TCO2 and negative correlation between pulmonary
      opacity score and blood PaO2 and SO2. Hence, it is possible to infer that
      neonatal hypoxia during prolonged calving has an imperative influence on
      pulmonary fluid absorption in calves. In conclusion, calving greater than 2 hours
      impacts pulmonary function at birth, leading to altered lung gas exchange,
      pulmonary clearance, cardiac and respiratory pattern. Conversely, obstetric
      intervention when calving has duration greater than 4 hours is beneficial for
      neonatal oxygenation.

PMID- 30226865
TI  - Correction: Divergence in the evolution of Paleolithic symbolic and technological
      systems: The shining bull and engraved tablets of Rocher de l'Imperatrice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0173037.].

PMID- 30226867
TI  - Modeling and impedance matching for radio frequency driven plasma lamp
      considering cold and hot states.
AB  - A new dual-state impedance matching scheme for a microwave driven plasma lamp
      using a solid-state power amplifier (SSPA) is presented. The impedance of the
      plasma lamp depends on the amount of input radio frequency (RF) energy, and
      therefore has very different values for hot and cold states. First, a method for
      effectively modeling the electrical characteristics of a plasma lamp that depends
      on RF power has been proposed. Second, a new technique has been proposed to
      achieve dual-state impedance matching for two state impedances at two very close
      frequencies using a T-shaped matching network with two section shunt stub and
      additional transmission line. The proposed method can achieve dual state
      impedance matching in two frequency bands located very closely when compared to
      the conventional methods. The accuracy of the proposed model and the
      effectiveness of the proposed dual-state matching are verified via a plasma lamp
      system with a 2.45 GHz 300 W GaN SSPA.

PMID- 30226866
TI  - Jagged1/Notch2 controls kidney fibrosis via Tfam-mediated metabolic
      reprogramming.
AB  - While Notch signaling has been proposed to play a key role in fibrosis, the
      direct molecular pathways targeted by Notch signaling and the precise ligand and
      receptor pair that are responsible for kidney disease remain poorly defined. In
      this study, we found that JAG1 and NOTCH2 showed the strongest correlation with
      the degree of interstitial fibrosis in a genome-wide expression analysis of a
      large cohort of human kidney samples. Transcript analysis of mouse kidney disease
      models, including folic-acid (FA)-induced nephropathy, unilateral ureteral
      obstruction (UUO), or apolipoprotein L1 (APOL1)-associated kidney disease,
      indicated that Jag1 and Notch2 levels were higher in all analyzed kidney fibrosis
      models. Mice with tubule-specific deletion of Jag1 or Notch2
      (Kspcre/Jag1flox/flox and Kspcre/Notch2flox/flox) had no kidney-specific
      alterations at baseline but showed protection from FA-induced kidney fibrosis.
      Tubule-specific genetic deletion of Notch1 and global knockout of Notch3 had no
      effect on fibrosis. In vitro chromatin immunoprecipitation experiments and genome
      wide expression studies identified the mitochondrial transcription factor A
      (Tfam) as a direct Notch target. Re-expression of Tfam in tubule cells prevented
      Notch-induced metabolic and profibrotic reprogramming. Tubule-specific deletion
      of Tfam resulted in fibrosis. In summary, Jag1 and Notch2 play a key role in
      kidney fibrosis development by regulating Tfam expression and metabolic
      reprogramming.

PMID- 30226868
TI  - A Delphi consultation to assess indicators of readiness to provide quality health
      facility-based lymphoedema management services.
AB  - BACKGROUND: The World Health Organization (WHO) in collaboration with partners is
      developing a toolkit of resources to guide lymphatic filariasis (LF) morbidity
      management and disability prevention (MMDP) implementation and evaluation. Direct
      health facility inspection is the preferred method for documenting the readiness
      of a country programme to provide quality lymphoedema management services, one of
      the three MMDP criteria used to demonstrate the elimination of LF as a public
      health problem. METHODOLOGY/PRINCIPAL FINDINGS: As component of tool development,
      a Delphi consultation was implemented to gain consensus on six proposed domains
      and fourteen proposed tracer indicators to measure national programme readiness
      to provide quality health facility-based lymphoedema management services. A seven
      point Likert-type scale was used to rank the importance of proposed domains and
      tracer indicators. Consensus for inclusion of the indicator was defined a priori
      as 70% or more of respondents ranking the proposed indicator in the top three
      tiers (5-7). Purposive sampling was used to select 43 representative experts
      including country representatives, programme implementers, and technical experts.
      A 55.8% response rate (n = 24) was achieved for the survey. Analysis of the
      responses demonstrated that consensus for inclusion had been reached for all
      proposed domains including trained staff (mean = 6.9, standard deviation (SD) =
      0.34), case management and education materials (mean = 6.1, SD = 0.65), water
      infrastructure (mean = 6.3, SD = 0.81), medicines and commodities (mean = 6.3, SD
      = 0.69), patient tracking system (mean = 6.3, SD = 0.85), and staff knowledge
      (mean = 6.5, SD = 0.66). SIGNIFICANCE: The Delphi consultation provided an
      efficient and structured method for gaining consensus among lymphatic filariasis
      experts around key lymphoedema management quality indicators. The results from
      this analysis were used to refine the indicators included within the direct
      inspection protocol tool to ensure its ability to assess health facility
      readiness to provide quality lymphoedema management services.

PMID- 30226869
TI  - Age affects myosin relaxation states in skeletal muscle fibers of female but not
      male mice.
AB  - The recent discovery that myosin has two distinct states in relaxed muscle
      disordered relaxed (DRX) and super-relaxed (SRX)-provides another factor to
      consider in our fundamental understanding of the aging mechanism in skeletal
      muscle, since myosin is thought to be a potential contributor to dynapenia (age
      associated loss of muscle strength independent of atrophy). The primary goal of
      this study was to determine the effects of age on DRX and SRX states and to
      examine their sex specificity. We have used quantitative fluorescence microscopy
      of the fluorescent nucleotide analog 2'/3'-O-(N-methylanthraniloyl) ATP (mantATP)
      to measure single-nucleotide turnover kinetics of myosin in skinned skeletal
      muscle fibers under relaxing conditions. We examined changes in DRX and SRX in
      response to the natural aging process by measuring the turnover of mantATP in
      skinned fibers isolated from psoas muscle of adult young (3-4 months old) and
      aged (26-28 months old) C57BL/6 female and male mice. Fluorescence decays were
      fitted to a multi-exponential decay function to determine both the time constants
      and mole fractions of fast and slow turnover populations, and significance was
      analyzed by a t-test. We found that in females, both the DRX and SRX lifetimes of
      myosin ATP turnover at steady state were shorter in aged muscle fibers compared
      to young muscle fibers (p <= 0.033). However, there was no significant difference
      in relaxation lifetime of either DRX (p = 0.202) or SRX (p = 0.804) between young
      and aged male mice. No significant effects were measured on the mole fractions
      (populations) of these states, as a function of sex or age (females, p = 0.100;
      males, p = 0.929). The effect of age on the order of myosin heads at rest and
      their ATPase function is sex specific, affecting only females. These findings
      provide new insight into the molecular factors and mechanisms that contribute to
      aging muscle dysfunction in a sex-specific manner.

PMID- 30226870
TI  - Clinical inertia in basal insulin-treated patients with type 2 diabetes - Results
      from a retrospective database study in Japan (JDDM 43).
AB  - AIMS: This retrospective cohort study investigated whether clinical inertia, the
      failure to intensify treatment when required, exists in Japanese clinical
      practice, using the CoDiC(r) database. How and when patients with type 2 diabetes
      treated with basal insulin received treatment intensification was also described.
      MATERIALS AND METHODS: Patients with type 2 diabetes who initiated basal insulin
      between 2004 and 2011 were eligible for inclusion. Patients with an HbA1c >=7.0%
      (>=53.0 mmol/mol) after 180 days of basal insulin titration were eligible for
      intensification, and their treatment was followed for up to 1.5 years. Endpoints
      were time to intensification, changes in HbA1c, and insulin dose. RESULTS:
      Overall, 2351 patients initiated basal insulin treatment (mean HbA1c 9.4% [79.2
      mmol/mol]), and 1279 patients were eligible for treatment intensification (HbA1c
      >=7.0% [>=53.0 mmol/mol]) after the 180-day titration period. During the 1.5-year
      follow-up period (beyond the 180-day titration period), 270 (21%) of these
      patients received treatment intensification. In patients receiving treatment
      intensification, mean HbA1c decreased from 8.6 to 8.2% (70.5 to 66.1 mmol/mol) at
      end of follow-up. Treatment was intensified using bolus insulin in 126 (47%)
      patients and with premixed insulin in 144 (53%) patients. The estimated
      probability of intensifying treatment during the 12 months after recording HbA1c
      >=7.0% (>=53.0 mmol/mol) was 22.8%, and 27.5% after 17 months. Mean end-of-follow
      up daily insulin dose was 35.11 units for basal-bolus compared with 20.70 units
      for premix therapy. CONCLUSIONS: This study suggests clinical inertia exists in
      basal insulin-treated patients with type 2 diabetes in Japan. Strategies are
      needed to increase the number of patients undergoing therapy intensification and
      to reduce the delay in intensification in Japan.

PMID- 30226871
TI  - An evaluation of the error and uncertainty in epibenthos cover estimates from AUV
      images collected with an efficient, spatially-balanced design.
AB  - Efficient monitoring of organisms is at the foundation of protected area and
      biodiversity management. Such monitoring programs are based on a systematically
      selected set of survey locations that, while able to track trends at those
      locations through time, lack inference for the overall region being "monitored".
      Advances in spatially-balanced sampling approaches offer alternatives but remain
      largely untested in marine ecosystems. This study evaluated the merit of using a
      two-stage, spatially-balanced survey framework, in conjunction with generalized
      additive models, to estimate epifauna cover at a reef-wide scale for mesophotic
      reefs within a large, cross-shelf marine park. Imagery acquired by an autonomous
      underwater vehicle was classified using a hierarchical scheme developed under the
      Collaborative and Automated Tools for Analysis of Marine Imagery (CATAMI). At a
      realistic image subsampling intensity, the two-stage, spatially-balanced
      framework provided accurate and precise estimates of reef-wide cover for a select
      number of epifaunal classes at the coarsest CATAMI levels, in particular bryozoan
      and porifera classes. However, at finer hierarchical levels, accuracy and/or
      precision of cover estimates declined, primarily because of the natural rarity of
      even the most common of these classes/morphospecies. Ranked predictor importance
      suggested that bathymetry, backscatter and derivative terrain variables
      calculated at their smallest analysis window scales (i.e. 81 m2) were generally
      the most important variables in the modeling of reef-wide cover. This study makes
      an important step in identifying the constraints and limitations that can be
      identified through a robust statistical approach to design and analysis. The two
      stage, spatially-balanced framework has great potential for effective
      quantification of epifaunal cover in cross-shelf mesophotic reefs. However,
      greater image subsampling intensity than traditionally applied is required to
      ensure adequate observations for finer-level CATAMI classes and associated
      morphospecies.

PMID- 30226872
TI  - Carnivore conservation needs evidence-based livestock protection.
AB  - Carnivore predation on livestock often leads people to retaliate. Persecution by
      humans has contributed strongly to global endangerment of carnivores. Preventing
      livestock losses would help to achieve three goals common to many human
      societies: preserve nature, protect animal welfare, and safeguard human
      livelihoods. Between 2016 and 2018, four independent reviews evaluated >40 years
      of research on lethal and nonlethal interventions for reducing predation on
      livestock. From 114 studies, we find a striking conclusion: scarce quantitative
      comparisons of interventions and scarce comparisons against experimental controls
      preclude strong inference about the effectiveness of methods. For wise investment
      of public resources in protecting livestock and carnivores, evidence of
      effectiveness should be a prerequisite to policy making or large-scale funding of
      any method or, at a minimum, should be measured during implementation. An
      appropriate evidence base is needed, and we recommend a coalition of scientists
      and managers be formed to establish and encourage use of consistent standards in
      future experimental evaluations.

PMID- 30226873
TI  - Comparison of the efficiency of various muscle transposition procedures using a
      novel three-dimensional model.
AB  - AIM: To investigate the performance of a newly developed three-dimensional (3D)
      biomechanical model in various transposition procedures for correction of
      complete sixth nerve palsy with educational purpose. METHODS: A 3D biomechanical
      eye model was created using Hyperworks software based on geometry data and the
      biochemical properties of the eyeball and extraocular muscles. A complete sixth
      nerve palsy model was achieved via modification of lateral rectus muscle
      strength. Four different muscle transposition procedures (the Hummelsheim,
      Jensen, Foster, and muscle union procedures) were set up, and the objective
      surgical effect of each procedure was calculated using 3D model simulation.
      RESULTS: In the 3D simulation, sixth nerve palsy was modeled by rotating the eye
      34.16 degrees in the medial direction, consistent with 70 prism diopter (PD)
      esotropia. In surgical model simulation, the Hummelsheim procedure resulted in a
      28 PD reduction of total deviation, the Jensen procedure achieved a 34 PD
      reduction, the Foster procedure led to a 57 PD reduction, the muscle union
      procedure yielded a 57 PD reduction in esotropia in sixth nerve palsy.
      CONCLUSION: The 3D simulation provided a consistent model of sixth nerve palsy
      and objective data excluding the potential for variation of surgical skill. It
      could also help predict surgical outcomes.

PMID- 30226874
TI  - Changes in human intervertebral disc biochemical composition and bony end plates
      between middle and old age.
AB  - OBJECTIVE: This study evaluates molecular, nutritional and biochemical
      alterations in human intervertebral discs between middle and old age. METHODS:
      Twenty-eight human lumbar intervertebral discs from donors were evaluated and
      separated into two groups: Middle-aged (35-50 years old, relatively non
      degenerate discs of Pfirrmann grades 1-3, n = 15) and Old-aged (>=80 years old,
      all degenerate Pfirrmann grade 4 or 5, n = 13). Parameters which might be
      expected to to be related to nutrient supply and so the health of disc cells (eg
      the porosity of the vertebral endplate, cell viability and cell density) and to
      disc extracellular composition (ie quantification of glycosaminoglycan
      disaccharides and hyaluronic acid molecular weight) and collagen organization,
      were analyzed. Three regions of the intervertebral disc (anterior annulus
      fibrosus, nucleus pulposus, and posterior annulus fibrosus) were examined.
      RESULTS: The old-aged group showed a decrease in content of sulphated and non
      sulphated glycosaminoglycans relative to middle-aged and there were also
      alterations in the proportion of GAG disaccharides and a decrease of collagen
      fiber size. Hyaluronic acid molecular weight was around 200 kDa in all regions
      and ages studied. The anterior annulus differed from the posterior annulus
      particularly in relation to cell density and GAG content. Additionally, there
      were changes in the bony endplate, with fewer openings observed in the caudal
      than cranial endplates of all discs in both groups. CONCLUSIONS: Results show the
      cranial vertebral endplate is the main vascular source for the intervertebral
      discs. Hylauronic acid molecular weight is the same through the intervertebral
      disc after age of 50 years.

PMID- 30226875
TI  - Digitizing extant bat diversity: An open-access repository of 3D MUCT-scanned
      skulls for research and education.
AB  - Biological specimens are primary records of organismal ecology and history. As
      such, museum collections are invaluable repositories for testing ecological and
      evolutionary hypotheses across the tree of life. Digitizing and broadly sharing
      the phenotypic data from these collections serves to expand the traditional reach
      of museums, enabling widespread data sharing, collaboration, and education at an
      unprecedented scale. In recent years, MUCT-scanning has been adopted as one way
      for efficiently digitizing museum specimens. Here, we describe a large repository
      of 3D, MUCT-scanned images and surfaces of skulls from 359 extant species of
      bats, a highly diverse clade of modern vertebrates. This digital repository spans
      much of the taxonomic, biogeographic, and morphological diversity present across
      bats. All data have been published to the MorphoSource platform, an online
      database explicitly designed for the archiving of 3D morphological data. We
      demonstrate one potential use of this repository by testing for convergence in
      skull shape among one particularly diverse group of bats, the superfamily
      Noctilionoidea. Beyond its intrinsic utility to bat biologists, our digital
      specimens represent a resource for educators and for any researchers seeking to
      broadly test theories of trait evolution, functional ecology, and community
      assembly.

PMID- 30226876
TI  - Viral etiology of acute respiratory infections in hospitalized children in
      Novosibirsk City, Russia (2013 - 2017).
AB  - BACKGROUND: Acute respiratory infections (ARIs) cause a considerable morbidity
      and mortality worldwide especially in children. However, there are few studies of
      the etiological structure of ARIs in Russia. In this work, we analyzed the
      etiology of ARIs in children (0-15 years old) admitted to Novosibirsk Children's
      Municipal Clinical Hospital in 2013-2017. METHODS: We tested nasal and throat
      swabs of 1560 children with upper or lower respiratory infection for main
      respiratory viruses (influenza viruses A and B, parainfluenza virus types 1-4,
      respiratory syncytial virus, metapneumovirus, four human coronaviruses,
      rhinovirus, adenovirus and bocavirus) using a RT-PCR Kit. RESULTS: We detected
      1128 (72.3%) samples were positive for at least one virus. The most frequently
      detected pathogens were respiratory syncytial virus (358/1560, 23.0%), influenza
      virus (344/1560, 22.1%), and rhinovirus (235/1560, 15.1%). Viral co-infections
      were found in 163 out of the 1128 (14.5%) positive samples. We detected
      significant decrease of the respiratory syncytial virus-infection incidence in
      children with increasing age, while the reverse relationship was observed for
      influenza viruses. CONCLUSIONS: We evaluated the distribution of respiratory
      viruses in children with ARIs and showed the prevalence of respiratory syncytial
      virus and influenza virus in the etiological structure of infections. This study
      is important for the improvement and optimization of diagnostic tactics, control
      and prevention of the respiratory viral infections.

PMID- 30226877
TI  - Age dependent normative data of vertical and horizontal reflexive saccades.
AB  - PURPOSE: There is some controversy whether or not saccades change with age. This
      cross-sectional study aims to clarify the characteristics of reflexive saccades
      at various ages to establish a normative cohort in a standardized set-up. Second
      objective is to investigate the feasibility of saccadometry in daily
      ophthalmological practice. METHODS: One hundred healthy participants aged between
      6 and 76 years underwent an ophthalmologic examination and saccadometry, using an
      infrared video-oculography device, sampling at 220 Hz. The reflexive saccades
      were evoked in four directions and three target displacements each (5 degrees /15
      degrees /30 degrees  horizontally and of 5 degrees /10 degrees /20 degrees 
      vertically). Saccadic peak velocity, gain (amplitude/target displacement) and
      latency were measured. RESULTS: Mean peak velocity of saccades was 213 degrees /s
      (+/- 29 degrees /s), 352 degrees /s (+/- 50 degrees /s) and 455 degrees /s (+/-
      67 degrees /s) to a target position 5 degrees , 15 degrees and 30 degrees 
      horizontally, respectively, and 208 degrees /s (+/- 36 degrees /s), 303 degrees
      /s (+/- 50 degrees /s) and 391 degrees /s (+/- 71 degrees /s) to a target
      position 5 degrees , 10 degrees  and 20 degrees  vertically. The association
      between peak velocity and eccentricity proved to be present at any age in all
      four directions. We found no relevant effect of age on peak velocity, gain and
      latency in a fitted linear mixed model. However, latency becomes shorter during
      childhood and adolescence, while in adulthood it is relatively stable with a
      slight trend to increase in the elderly. Saccades are more precise when the
      target displacement is small. Isometric saccades are most common, followed by
      hypometric ones. All children and elderly were able to perform good quality
      saccadometry in a recording time of approximately 10 minutes. CONCLUSION: The
      presented data may serve as normative control for further studies using such a
      video-oculography device for saccadometry. The means of peak velocity and the
      gain can be used independently from age respecting the target displacement.
      Latency is susceptible to age.

PMID- 30226878
TI  - Exploring health literacy and preferences for risk communication among medical
      oncology patients.
AB  - OBJECTIVE: To explore adult medical oncology outpatients' understanding of and
      preferences for the format of health risk information. METHODS: Two surveys, one
      assessing sociodemographic characteristics and a second survey examining
      perceptions of risk information. RESULTS: Of the 361 (74%) consenting patients,
      210 completed at least one question on risk communication. 17% to 65% of patients
      understood numeric risk information, depending on the format of the information.
      More than 50% of people interpreted a "very good" chance of remission as greater
      than 80%, greater than 90% or 100%. The most preferred format of information was
      in both words and numbers (38% to 43%) followed by words alone (28% to 30%).
      CONCLUSION: Numeric risk information is understood by 17% to 65% of respondents,
      depending on the format. Interpretation of verbal risk information is highly
      variable, posing a risk of misunderstanding. Provision of information in both
      words and numbers may assist in aiding comprehension.

PMID- 30226879
TI  - Macroalgae size refuge from herbivory promotes alternative stable states on coral
      reefs.
AB  - Coral reef systems can undergo rapid transitions from coral-dominated to
      macroalgae-dominated states following disturbances, and models indicate that
      these may sometimes represent shifts between alternative stable states. While
      several mechanisms may lead to alternate stable states on coral reefs, only a few
      have been investigated theoretically. We explore a model that illustrates that
      reduced vulnerability of macroalgae to herbivory as macroalgae grow and mature
      could be an important mechanism: when macroalgae are palatable to herbivores as
      juveniles, but resistant as adults, coral-dominated and algae-dominated states
      are bistable across a wide range of parameter space. We compare two approaches to
      global sensitivity analysis to rank the relative importance of the model
      parameters in determining the presence and magnitude of alternative stable
      states, and find that the two most influential parameters are the death rate of
      coral and the rate of maturation of algae out of the vulnerable stage. The Random
      Forest approach for global sensitivity analysis, recently adopted by ecologists,
      provides a more efficient method for ranking the relative importance of
      parameters than a variance-based approach that has been used frequently by
      computer scientists and engineers. Our results suggest that managing reefs to
      reduce chronic stressors that cause coral mortality and/or enhance the growth
      rates of algae can help prevent reefs from becoming locked in a macroalgae
      dominated state.

PMID- 30226880
TI  - Clinical manifestations of dengue in relation to dengue serotype and genotype in
      Malaysia: A retrospective observational study.
AB  - BACKGROUND: Malaysia experienced an unprecedented dengue outbreak from the year
      2014 to 2016 that resulted in an enormous increase in the number of cases and
      mortality as compared to previous years. The causes that attribute to a dengue
      outbreak can be multifactorial. Viral factors, such as dengue serotype and
      genotype, are the components of interest in this study. Although only a small
      number of studies investigated the association between the serotype of dengue
      virus and clinical manifestations, none of these studies included analyses on
      dengue genotypes. The present study aims to investigate dengue serotype and
      genotype-specific clinical characteristics among dengue fever and severe dengue
      cases from two Malaysian tertiary hospitals between 2014 and mid-2017.
      METHODOLOGY AND PRINCIPAL FINDINGS: A total of 120 retrospective dengue serum
      specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR,
      sequencing and phylogenetic analysis. Subsequently, the dengue serotype and
      genotype data were statistically analyzed for 101 of 120 corresponding patients'
      clinical manifestations to generate a descriptive relation between the genetic
      components and clinical outcomes of dengue infected patients. During the study
      period, predominant dengue serotype and genotype were found to be DENV 1 genotype
      I. Additionally, non-severe clinical manifestations were commonly observed in
      patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2
      infection showed significant warning signs and developed severe dengue (p =
      0.007). Cases infected with DENV 2 were also commonly presented with persistent
      vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and
      shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among
      DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific
      clinical manifestations showed that DENV 2 Cosmopolitan was significantly common
      among severe dengue patients. An association was also found between genotype I of
      DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly
      common among patients with arthralgia. CONCLUSION: The current data contended
      that different dengue serotype and genotype had caused distinct clinical
      characteristics in infected patients.

PMID- 30226882
TI  - Correction: Percutaneous thermal ablation combined with TACE versus TACE
      monotherapy in the treatment for liver cancer with hepatic vein tumor thrombus: A
      retrospective study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0201525.].

PMID- 30226881
TI  - Maternal feeding practices in relation to dietary intakes and BMI in 5 year-olds
      in a multi-ethnic Asian population.
AB  - BACKGROUND: In Asia, little is known about how maternal feeding practices are
      associated with dietary intakes and body mass index (BMI) in preschoolers.
      OBJECTIVE: To assess the relationships between maternal feeding practices with
      dietary intakes and BMI in preschoolers in Asia using cross-sectional analysis in
      the GUSTO (Growing Up in Singapore Towards healthy Outcomes) cohort. PARTICIPANT
      SETTINGS: Mothers (n = 511) who completed the Comprehensive Feeding Practices
      Questionnaire (CFPQ) and a semi-quantitative Food Frequency Questionnaire (FFQ)
      when children were 5 years old. STATISTICAL ANALYSIS: Associations between 12
      maternal feeding practices (mean scores divided into tertiles) and children's
      dietary intakes of seven food groups and BMI z-scores were examined using the
      general linear regression model. Weight and height of the child were measured,
      and dietary intakes derived from the FFQ. RESULTS: Compared to those in the low
      tertile, mothers in the high tertile of modelling healthy food intakes had
      children with higher intakes of vegetables[+20.0g/day (95%CI:11.6,29.5)] and
      wholegrains[+ 20.9g/day (9.67,31.1)] but lower intakes of sweet snacks[-10.1g/day
      (-16.3,-4.94)] and fast-foods[-5.84g/day (-10.2,-1.48)]. Conversely, children of
      mothers in the high tertile for allowing child control (lack of parental control)
      had lower intake of vegetables[-15.2g/day (-26.6,-5.21)] and wholegrains[
      13.6g/day (-22.9,-5.27)], but higher intakes of sweet snacks[+13.7g/day (7.7,
      19.8)] and fast-foods[+6.63g/day (3.55,9.72)]. In relation to BMI at 5 years,
      food restrictions for weight was associated with higher BMI z-scores [0.86SD
      (0.61,1.21)], while use of pressure was associated with lower BMI z-scores[
      0.49SD(-0.78,-0.21)]. CONCLUSIONS AND IMPLICATIONS: Modelling healthy food
      intakes by mothers was the key feeding practice associated with higher intakes of
      healthy foods and lower intakes of discretionary foods. The converse was true for
      allowing child control. Only food restrictions for weight and use of pressure
      were associated with BMI z-scores.

PMID- 30226883
TI  - Changes in the optic nerve head induced by horizontal eye movements.
AB  - PURPOSE: To investigate the effect of eye movement on the optic nerve head (ONH)
      using swept-source optical coherence tomography (SS-OCT), and to measure the
      degree of ONH changes. METHODS: We enrolled 52 healthy subjects, 20 to 40 years
      of age, and performed a prospective observational study. Both ONH and macula were
      imaged simultaneously using wide volume scan of the SS-OCT in the primary and
      different gaze positions. Horizontal eye movements were used to obtain OCT images
      in abducted and adducted eyeball positions. Multilateral 3-dimensional
      registration was used to process and analyze the images to measure the degree of
      ONH changes. RESULTS: The mean axial length (AXL) was 25.73 +/- 1.42mm and the
      mean spherical equivalents was -4.49 +/- 2.94 D (The proportion of high myopia
      was 39.4%). Significant morphologic changes were observed in the ONH during both
      abduction and adduction. In abduction, the overall ONH tissues were elevated, and
      the mean area of elevation was 115,134 +/- 9,424 MUm2 (p<0.001). In adduction,
      the mean areas from two perspectives, which were nasal or temporal, and
      peripapillary tissues or optic nerve cupping were 95,277 +/- 73,846 MUm2, 34,450
      +/- 44,948 MUm2, -108,652 +/- 91,246 MUm2, and -30,581 +/- 46,249 MUm2,
      respectively. Elevation in abduction (overall, nasal cup segment, and temporal
      cup segment; R = 0.204, 0.195 and 0.225, p = 0.038, 0.047 and 0.021,
      respectively) and elevation of nasal peripapillary segments in adduction were
      positively correlated with AXL (R = 0.346, p<0.001). CONCLUSION: We found
      significant morphologic changes in the ONH in both abduction and adduction and
      these changes were associated with AXL. Considering these morphologic changes as
      physical properties, it allows a better understanding of the biomechanical
      characteristics of the ONH.

PMID- 30226884
TI  - CLEC16A regulates splenocyte and NK cell function in part through MEK signaling.
AB  - CLEC16A is implicated in multiple autoimmune diseases. We generated Clec16a
      inducible knockout (KO) mice to examine the functional link between CLEC16A auto
      inflammation and autoimmunity. Clec16a KO mice exhibited weight loss and thymic
      and splenic atrophy. Mitochondrial potential was lowered in KO mice splenocytes
      resulting in aggregation of unhealthy mitochondria in B, T, and NK cells. In
      Clec16a KO mice we detected disrupted mitophagy in splenic B and T cells. NK
      cells from Clec16a KO mice exhibited increased cytotoxicity. Incomplete mitophagy
      was attenuated with PI3K and/or MEK inhibition in Clec16a KO mice. Our results
      demonstrate a functional link between CLEC16A and disrupted mitophagy in immune
      cells and show that incomplete mitophagy predisposes the KO mice to inflammation.
      Taken together, loss of function variants in CLEC16A that are associated with
      decreased CLEC16A expression levels may contribute to inflammation in
      autoimmunity through disrupted mitophagy. Drugs modulating mitophagy reverse the
      process and may be effective in treating and preventing autoimmunity in
      individuals with risk associated CLEC16A variants.

PMID- 30226885
TI  - Trends in polypharmacy over 12 years and changes in its social gradients in South
      Korea.
AB  - Polypharmacy is associated with adverse drug reactions and represents an economic
      burden on the health insurance system. The objective of our study was to assess
      the trends in polypharmacy and its associated factors in South Korea. This cross
      sectional study used a nationwide sampled database between 2002 and 2013,
      including outpatients of all ages who received at least 1 prescription in the
      same period. Polypharmacy was defined as the concomitant prescription of >=6
      distinct medications on a single prescription at least once without a given
      duration. The yearly prescribing trends were calculated and plotted. We conducted
      comparative analyses to identify the changes in social gradients of polypharmacy
      between the first 2 years, 2002-2003, and the final 2 years, 2012-2013. We
      repeated logistic regressions for pediatrics <20 years of age and adults >=20
      years of age to estimate the adjusted odds ratios (aOR) and 95% confidence
      intervals (CI). The distributions of polypharmacy in the respective periods were
      examined according to patient economic status (0 = most deprived and 10 = most
      affluent). The age-standardized prevalence of polypharmacy decreased from 65.8%
      in 2002 to 43.7% in 2013. Our study included 1,108,298 outpatients throughout
      2002-2013. Pediatric patients aged 1-9 years had the highest number of
      medications among all age groups (mean: 5.1 +/- 1.1 in 2002-2003 vs. 4.1 +/- 1.1
      in 2012-2013) in both periods. Changes in the association between deprivation and
      polypharmacy over 10 years were observed in adults (aOR = 0.68; 95% CI = 0.62
      0.75 in 2002-2003 vs. 1.60; 95% CI = 1.54-1.66 in 2012-2013) and pediatrics (aOR
      = 0.60; 95% CI = 0.52-0.68 in 2002-2003 vs. 1.07; 95% CI = 1.01-1.14 in 2012
      2013) compared with those in the most affluent patients. The high level of
      polypharmacy in pediatric patients is a public health concern that warrants
      policymaker attention.

PMID- 30226886
TI  - Altered functional connectivity within the default mode network in two animal
      models with opposing episodic memories.
AB  - Memory enhancement and memory decline are two opposing cognitive performances
      commonly observed in clinical practice, yet the neural mechanisms underlying
      these two different phenomena remain poorly understood. Accumulating evidence has
      demonstrated that the default-mode network (DMN) is implicated in diverse
      cognitive, social, and affective processes. In the present study, we used the
      retrosplenial cortex as a seed region to study the functional connectivity within
      the DMN in two animal models with opposing episodic memories, of which memory
      enhancement was induced by footshocks to mimic posttraumatic stress disorder
      (PTSD) and memory decline was induced by lipopolysaccharide (LPS) challenge to
      mimic sepsis-associated encephalopathy (SAE). Our results showed that LPS
      challenge and footshocks induced opposing episodic memories. With regard to the
      imaging data, there were significant differences in the functional connectivity
      between the retrosplenial cortex and the medial prefrontal cortex (mPFC), insular
      lobe, left piriform cortex, left sensory cortex, and right visual cortex among
      the three groups. Post-hoc comparisons showed the LPS group had a significantly
      increased functional connectivity between the retrosplenial cortex and mPFC as
      compared with the control group. Compared with the LPS group, the PTSD group
      displayed significantly decreased functional connectivity between the
      retrosplenial cortex and the right visual cortex, retrosplenial cortex, insular
      lobe, left piriform cortex, and left sensory cortex. In summary, our study
      suggests that there is a significant difference in the functional connectivity
      within the DMN between SAE and PTSD rats.

PMID- 30226887
TI  - Exposure to trips and slips with increasing unpredictability while walking can
      improve balance recovery responses with minimum predictive gait alterations.
AB  - INTRODUCTION: The primary study aim was to determine if repeated exposure to
      trips and slips with increasing unpredictability while walking can improve
      balance recovery responses when predictive gait alterations (e.g. slowing down)
      are minimised. The secondary aim was to determine if predictive gait alterations
      acquired through exposure to perturbations at a fixed condition would transfer to
      highly unpredictable conditions. METHODS: Ten young adults were instructed to
      step on stepping tiles adjusted to their usual step length and to a metronome
      adjusted to their usual cadence on a 10-m walkway. Participants were exposed to a
      total of 12 slips, 12 trips and 6 non-perturbed trials in three conditions: 1)
      right leg fixed location, 2) left leg fixed location and 3) random leg and
      location. Kinematics during non-perturbed trials and pre- and post-perturbation
      steps were analysed. RESULTS: Throughout the three conditions, participants
      walked with similar gait speed, step length and cadence(p>0.05). Participants'
      extrapolated centre of mass (XCoM) was anteriorly shifted immediately before
      slips at the fixed location (p<0.01), but this predictive gait alteration did not
      transfer to random perturbation locations. Improved balance recovery from trips
      in the random location was indicated by increased margin of stability and step
      length during recovery steps (p<0.05). Changes in balance recovery from slips in
      the random location was shown by reduced backward XCoM displacement and reduced
      slip speed during recovery steps (p<0.05). CONCLUSIONS: Even in the absence of
      most predictive gait alterations, balance recovery responses to trips and slips
      were improved through exposure to repeated unpredictable perturbations. A common
      predictive gait alteration to lean forward immediately before a slip was not
      useful when the perturbation location was unpredictable. Training balance
      recovery with unpredictable perturbations may be beneficial to fall avoidance in
      everyday life.

PMID- 30226888
TI  - Association between age at onset of independent walking and objectively measured
      sedentary behavior is mediated by moderate-to-vigorous physical activity in
      primary school children.
AB  - OBJECTIVE: Age at onset of walking has been shown as an early predictor of
      physical activity in infants and children. However, little is known about whether
      age at onset of walking may predict sedentary behavior (SB). The aim of the
      present study was to examine the association between the timing of onset of
      walking and objectively measured SB, and whether this association is mediated by
      moderate-to-vigorous physical activity (MVPA) in children. METHODS: The subjects
      were 388 elementary school children aged 6-12 years. Current weight and height
      data were collected. Birth weight and the age in months the child first walked
      independently were reported based on the parents' recall. Children's SB and
      physical activity were objectively measured using a triaxial accelerometer
      (Active style Pro HJA-350IT, OMRON). The following summary outcome variables were
      derived from accelerometer data: Time (min/day) spent in SB (<=1.5 metabolic
      equivalents [METs]) and MVPA (>=3.0 METs). RESULTS: The mean +/- SD time
      (min/day) spent in sedentary was 376 +/- 62 and MVPA was 67.6 +/- 20.8. Multiple
      linear regression analyses revealed that a later age at independent walking was
      associated with increased time spent in SB (beta = 0.15, P < 0.001) and decreased
      time spent in MVPA (beta = -0. 18, P < 0.001) after adjusting for gender, birth
      weight, current age, body weight, schools, and time spent wearing the
      accelerometer. When MVPA was introduced as a covariate in the model predicting
      SB, the association between the age at independent walking and time spent in SB
      was completely attenuated (beta = 0.04, P = 0.215), while MVPA was significantly
      associated with SB (beta = -0.61, P < 0.001). CONCLUSIONS: Our results indicate
      that infants who walked at a later age spent more time in SB in childhood, and
      this association is mediated by MVPA. Appropriate interventions which focus on
      increasing MVPA and thereby reducing SB may be beneficial in infants who
      demonstrate a later age at onset of independent walking.

PMID- 30226889
TI  - Prevalence of hepatic steatosis as assessed by controlled attenuation parameter
      (CAP) in subjects with metabolic risk factors in primary care. A population-based
      study.
AB  - BACKGROUND: Primary care is the ideal setting for early identification of
      patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is a potentially
      progressive disease that may lead to cirrhosis and liver cancer but is frequently
      underrecognized because subjects at risk are often not evaluated. Controlled
      attenuation parameter (CAP) is a reliable method for non-invasive quantification
      of liver fat. It has the advantage of simultaneous measurement of liver stiffness
      (LS), an estimate of liver fibrosis. There is no information on CAP in subjects
      with risk factors from primary care. AIM: To investigate the prevalence of
      hepatic steatosis, as estimated by CAP, in subjects from the community with
      metabolic risk factors and correlate findings with clinical and biochemical
      characteristics and LS. PATIENTS AND METHODS: Population-based study of 215
      subjects with metabolic risk factors without known liver disease identified
      randomly from a primary care center. A control group of 80 subjects matched by
      age and sex without metabolic risk factors was also studied. CAP and LS were
      assessed using Fibroscan. RESULTS: Subjects with risk factors had CAP values
      higher than those of control group (268+/-64 vs 243+/-49dB/m,p<0.001). Prevalence
      of severe steatosis (CAP> 280dB/m) in subjects with risk factors was 43%. In
      multivariate analysis, fatty liver index (FLI) and HOMA were independent
      predictive factors of severe steatosis. There was a direct correlation between
      CAP and FLI values (r = 0.52,p<0.001). Interestingly, prevalence of increased LS
      was 12.6% in the risk group vs 0% in the control group (p<0.001). Increased LS
      occurred predominantly in subjects with high CAP values. CONCLUSIONS: A high
      proportion of subjects with metabolic risk factors seen in primary care have
      severe steatosis. FLI could be used as a surrogate of CAP. Increased LS was found
      in a significant proportion of subjects with risk factors but not in control
      subjects.

PMID- 30226890
TI  - Outbreak of human brucellosis in Southern Brazil and historical review of data
      from 2009 to 2018.
AB  - BACKGROUND: Human brucellosis (HB) is a bacterial zoonosis that is more frequent
      in low income and middle-income countries; it is sometimes associated with
      outbreaks. The aim of this study was to describe the largest outbreak of HB in
      Brazil. METHODS: A retrospective cohort study of patients suspected of having
      contracted HB in the state of Parana, Southern Brazil from January 2009 to
      January 2017. Following an outbreak of 51 cases of HB in a slaughterhouse at
      Paicandu in 2014, HB was defined as an obligatory reportable disease in the
      State. Diagnostic tests for HB included serum agglutination, ELISA (IgG or IgM)
      and polymerase chain reaction (PCR). Clinical, laboratorial and epidemiological
      data were analyzed. A P value of 0.05 was considered statistically significant.
      RESULTS: Out of a total of 3,941 patients, 754 presented with a positive test
      result for HB. After 2014, there was a significant increase in the number of
      cases, exceeding 100 cases per trimester. In the beginning of 2015, the workgroup
      of HB started several actions for prevention and treatment, and the number of
      cases progressively diminished to fewer than 20 cases per trimester. Of 191
      reported cases, an occupational risk was found in 84.7%; most cases occurred in
      farmers (60.0%), veterinarians (17.6%) and slaughterhouse workers (14.7%).
      Manipulation of animals and unpasteurized milk consumption were associated with
      positive Brucella IgM ELISA with an odds ratio (OR) of 1.42 (1.09-1.84) and 1.48
      (1.01-2.15), respectively. CONCLUSIONS: HB outbreaks can occur in low to middle
      income countries and are associated with slaughterhouse work, handling of
      unpasteurized milk and animal manipulation. Intensive programs for control of HB
      are important to reduce the number of cases.

PMID- 30226891
TI  - Assessing atmospheric nitrogen losses with photoacoustic infrared spectroscopy:
      Polymer coated urea.
AB  - Although N is beneficial and essential for life, it is also a common atmospheric
      pollutant as nitrous oxide (N2O) and ammonia (NH3)-contributed largely from N
      fertilization. Polymer-coated urea (PCU) fertilizer is a promising controlled
      release fertilizer that provides improved N-release timing. Glasshouse studies
      were conducted to compare N2O and NH3 emissions from PCU and uncoated urea to an
      untreated control utilizing a non-static, non-flow-through chamber in conjunction
      with photoacoustic infrared spectroscopy (PAIRS) for gas collection and analysis.
      Three short-term 20-Day Studies with sand, sandy loam, and loam soils and a full
      term 45-Day Study with loam soil were completed. Volatilization of NH3 was
      reduced by 72% and 22% in the sandy loam and loam soils, respectively, in two of
      the short-term studies and by 14% in the loam in the full-term study. Evolution
      of N2O was reduced by 42% and 63% in the sandy loam and loam soils of the short
      term studies and by 99% in the loam soil of the full-term study. No differences
      were observed in the sand soil. Overall, PCU decreased gaseous losses of N
      following fertilization while providing a steady supply of N to the plant. Higher
      temporal resolution was observed with the PAIRS instrumentation as compared to
      what is typically reported and, as such, we recommend PAIRS analysis as a viable
      method for studying N gas emissions.

PMID- 30226892
TI  - The relationship of self-efficacy to catastrophizing and depressive symptoms in
      community-dwelling older adults with chronic pain: A moderated mediation model.
AB  - Self-efficacy has been consistently found to be a protective factor against
      psychological distress and disorders in the literature. However, little research
      is done on the moderating effect of self-efficacy on depressive symptoms in the
      context of chronic pain. This cross-sectional study aimed to examine if pain self
      efficacy attenuated the direct relationship between pain intensity and depressive
      symptoms, as well as their indirect relationship through reducing the extent of
      catastrophizing when feeling pain (moderated mediation). 664 community-dwelling
      Chinese older adults aged 60-95 years who reported chronic pain for at least
      three months were recruited from social centers. They completed a battery of
      questionnaires on chronic pain, pain self-efficacy, catastrophizing, and
      depressive symptoms in individual face-to-face interviews. Controlling for age,
      gender, education, self-rated health, number of chronic diseases, pain
      disability, and pain self-efficacy, pain catastrophizing was found to partially
      mediate the connection between pain intensity and depressive symptoms.
      Furthermore, the relationship between pain intensity and depressive symptoms was
      moderated by pain self-efficacy. Self-efficacy was also found to moderate the
      relationship between pain intensity and catastrophizing and the moderated
      mediation effect was confirmed using bootstrap analysis. The results suggested
      that with increasing levels of self-efficacy, pain intensity's direct effect on
      depressive symptoms and its indirect effect on depressive symptoms via
      catastrophizing were both reduced in a dose-dependent manner. Our findings
      suggest that pain self-efficacy is a significant protective factor that
      contributes to psychological resilience in chronic pain patients by attenuating
      the relationship of pain intensity to both catastrophizing and depressive
      symptoms.

PMID- 30226893
TI  - Molecular characterization and expression of six heat shock protein genes in
      relation to development and temperature in Trichogramma chilonis.
AB  - Trichogramma is a kind of egg parasitoid wasp that is widely used to control
      lepidopterous pests. Temperature is one of the main factors that determines the
      various life activities of this species, including development, reproduction and
      parasitism efficiency. Heat shock proteins (HSPs) are highly conserved and
      ubiquitous proteins that are best known for their responsiveness to temperature
      and other stresses. To explore the potential role of HSPs in Trichogramma
      species, we obtained the full-length cDNAs of six HSP genes (Tchsp10, Tchsp21.6,
      Tchsp60, Tchsp70, Tchsc70-3, and Tchsp90) from T. chilonis and analyzed their
      expression patterns during development and exposure to temperature stress. The
      deduced amino acid sequences of these HSP genes contained the typical signatures
      of their corresponding protein family and showed high homology to their
      counterparts in other species. The expression levels of Tchsp10, Tchsp21.6 and
      Tchsp60 decreased during development. However, the expression of Tchsc70-3
      increased from the pupal stage to the adult stage. Tchsp70 and Tchsp90 exhibited
      the highest expression levels in the adult stage. The expression of six Tchsps
      was dramatically upregulated after 1 h of exposure to 32 and 40 degrees C but did
      not significantly change after 1 h of exposure to 10 and 17 degrees C. This
      result indicated that heat stress, rather than cold stress, induced the
      expression of HSP genes. Furthermore, the expression of these genes was time
      dependent, and the expression of each gene reached its peak after 1 h of heat
      exposure (40 degrees C). Tchsp10 and Tchsp70 exhibited a low-intensity cold
      response after 4 and 8 h of exposure to 10 degrees C, respectively, but the other
      genes did not respond to cold at any time points. These results suggested that
      HSPs may play different roles in the development of this organism and in its
      response to temperature stress.

PMID- 30226894
TI  - Characterizing conflict between humans and big cats Panthera spp: A systematic
      review of research trends and management opportunities.
AB  - Conservation of big cats (Panthera spp.), a taxonomic group including tigers,
      lions, jaguars, leopards and snow leopards, is a daunting challenge. As expanding
      human populations across Panthera range countries exacerbate competition for land
      and prey, conflicts between humans and big cats are inevitable. Through a
      systematic review of the peer-reviewed literature published from 1991 to 2014 and
      indexed in Web of Science and Google Scholar (186 articles), our study explored
      the current state of knowledge regarding human-Panthera conflict and potential
      solutions, examining variables such as spatial and temporal distribution of
      research, methods used to study conflict, evaluation of interventions, and
      management recommendations. Our synthesis revealed several key data gaps and
      research needs. More studies could utilize diverse data collection approaches to
      focus on both the ecological and socio-cultural context for conflict.
      Additionally, only 21% of articles included in the review evaluated conflict
      mitigation interventions, and few of these yielded conclusive results. Success
      ratios suggest that compensation schemes and livestock management strategies were
      more effective tools for addressing conflict than either direct interventions
      (lethal removal or translocation of animals) or community interventions (e.g.
      education, ecotourism, local management). More studies should systematically
      evaluate the efficacy of conflict mitigation strategies, many of which are
      consistently recommended without empirical support. Results highlight trends and
      opportunities that can be used to inform future research and management efforts
      focused on human-Panthera conflict, ultimately enhancing the potential for
      coexistence between humans and carnivore species worldwide.

PMID- 30226895
TI  - Expression profile of plasma microRNAs and their roles in diagnosis of mild to
      severe traumatic brain injury.
AB  - Traumatic brain injury (TBI) is associated with trauma-related death. In this
      study, we evaluated differences in the expression of plasma microRNAs (miRNAs) in
      patients with different degrees of TBI, and explored the potential of miRNAs for
      use as diagnostic TBI biomarkers. The miRNA microarray results showed
      upregulation of 65, 33, and 16 miRNAs and downregulation of 29, 27, and 6 miRNAs
      in patients with mild, moderate, and severe TBI, respectively, compared with
      healthy controls. Thirteen miRNAs (seven upregulated and six downregulated) were
      found to be present in all TBI groups. Seven upregulated miRNAs were selected for
      validation in an enlarged cohort of samples and showed good diagnostic accuracy.
      The expression levels of miR-3195 and miR-328-5p were higher in the severe TBI
      group than in the mild and moderate TBI groups. In summary, our study
      demonstrates different expression profiles in plasma miRNAs among patients with
      mild to severe TBI. A subset of seven miRNAs can be used for diagnosis of TBI.
      Moreover, miR-3195 and miR-328-5p may be utilized during diagnosis to distinguish
      mild and moderate TBI from severe TBI.

PMID- 30226896
TI  - Increased mortality in CD43-deficient mice during sepsis.
AB  - CD43 is a large transmembrane protein involved in T cell activation. Previous
      studies of CD43-/- mice in viral models have demonstrated a role for CD43 in
      Th1/Th2 skewing, activation of Foxp3+ Treg, and T cell apoptosis. However, the
      role of CD43 during sepsis has never been tested. Thus, we interrogated the role
      of CD43 during sepsis using a murine cecal ligation and puncture (CLP) model, and
      found that CD43-/- mice demonstrated significantly worsened mortality compared to
      B6 mice following CLP. Phenotypic analysis of splenocytes isolated 24 h after
      septic insult revealed significantly increased apoptosis of central memory cells
      in both CD4+ and CD8+ T cell compartments in CD43-/- septic mice compared to WT
      septic mice. Furthermore, CD43-/-septic mice exhibited a prominent Th2 skewing
      following sepsis relative to WT septic mice, as evidenced by a significant
      decrease in the frequency of IL-2+ CXCR3+ TH1 cells as a significant increase in
      the frequency of IL-4+ CCR4+ TH2 cells. Finally, septic CD43-/- animals contained
      significantly fewer CD25+ Foxp3+ TReg cells as compared to WT septic animals.
      Importantly, depleting CD25+ Treg eliminated the increased mortality observed in
      CD43-/- mice. Taken together, these data demonstrate an important role of CD43 in
      modulating immune dysregulation and mortality following sepsis.

PMID- 30226897
TI  - Etersalate prevents the formations of 6Abeta16-22 oligomer: An in silico study.
AB  - Oligomerization of amyloid beta (Abeta) peptides has been considered as the
      crucially causative agent in the development of Alzheimer's disease. Etersalate,
      a nonsteroidal anti-inflammatory oral drug (United State Food and Drug
      Administration-Unique Ingredient Identifier: 653GN04T2G) was previously suggested
      to bind well to proto-fibrils of Abeta peptides in silico. Here, the effect of
      etersalate on the oligomerization of soluble Abeta16-22 hexamer (6Abeta16-22)
      were extensively investigated using temperature replica exchange molecular
      dynamics (REMD) simulations over ~16.8 MUs in total for 48 replicas (350 ns per
      replica). The results reveal that etersalate can enter the inner space or bind on
      the surface of 6Abeta16-22 conformations, which destabilizes the hexamer.
      Etersalate was predicted to able to cross the blood brain barrier using
      prediction of absorption, distribution, metabolism, and excretion-toxicity
      (preADMET) tools. Overall, although the investigation was performed with the low
      concentration of trial inhibitor, the obtained results indicate that etersalate
      is a potential drug candidate for AD through inhibiting formation of Abeta
      oligomers with the average binding free energy of -11.7 kcal/mol.

PMID- 30226898
TI  - Triggered radiosensitizer delivery using thermosensitive liposomes and
      hyperthermia improves efficacy of radiotherapy: An in vitro proof of concept
      study.
AB  - INTRODUCTION: To increase the efficacy of chemoradiation and decrease its
      toxicity in normal tissue, a new concept is proposed, local radiosensitizer
      delivery, which combines triggered release of a radiosensitizer from
      thermosensitive liposomes with local hyperthermia and radiotherapy. Here, key
      aspects of this concept were investigated in vitro I) the effect of hyperthermia
      on the enhancement of radiotherapy by ThermoDox (thermosensitive liposome
      containing doxorubicin), II) the concentration dependence of the radiosensitizing
      effect of doxorubicin and III) the sequence of doxorubicin, hyperthermia and
      radiotherapy maximizing the radiosensitizing effect. METHODS: Survival of HT1080
      (human fibrosarcoma) cells was measured after exposure to ThermoDox or
      doxorubicin for 60 minutes, at 37 or 43 degrees C, with or without irradiation.
      Furthermore, cell survival was measured for cells exposed to different
      doxorubicin concentrations and radiation doses. Finally, cell survival was
      measured after applying doxorubicin and/or hyperthermia before or after
      irradiation. Cell survival was measured by clonogenic assay. In addition, DNA
      damage was assessed by gammaH2AX staining. RESULTS: Exposure of cells to
      doxorubicin at 37 degrees C resulted in cell death, but exposure to ThermoDox at
      37 degrees C did not. In contrast, ThermoDox and doxorubicin at 43 degrees C
      resulted in similar cytotoxicity, and in combination with irradiation caused a
      similar enhancement of cell kill due to radiation. Doxorubicin enhanced the
      radiation effect in a small, but significant, concentration-dependent manner.
      Hyperthermia showed the strongest enhancement of radiation effect when applied
      after irradiation. In contrast, doxorubicin enhanced radiation effect only when
      applied before irradiation. Concurrent doxorubicin and hyperthermia immediately
      before or after irradiation showed equal enhancement of radiation effect.
      CONCLUSION: In vitro, ThermoDox resulted in cytotoxicity and enhancement of
      irradiation effect only in combination with hyperthermia. Therefore hyperthermia
      triggered radiosensitizer release from thermosensitive liposomes may ultimately
      serve to limit toxicities due to the radiosensitizer in unheated normal tissue
      and result in enhanced efficacy in the heated tumor.

PMID- 30226899
TI  - SYBR Gold dye enables preferential labelling of mitochondrial nucleoids and their
      time-lapse imaging by structured illumination microscopy.
AB  - Mitochondrial DNA molecules coated with proteins form compact particles called
      mitochondrial nucleoids. They are redistributed within mitochondrial network
      undergoing morphological changes. The straightforward technique to characterize
      nucleoids' motions is fluorescence microscopy. Mitochondrial nucleoids are
      commonly labelled with fluorescent protein tags, which is not always feasible and
      was reported to cause artifacts. Organic DNA-binding dyes are free of these
      drawbacks, but they lack specificity to mitochondrial DNA. Here, considering
      physico-chemical properties of such dyes, we achieved preferential live-cell
      labelling of mitochondrial nucleoids by a nucleic acid staining dye SYBR Gold. It
      enabled time-lapse imaging of mitochondrial nucleoids by structured illumination
      microscopy and quantification of their motions.

PMID- 30226900
TI  - Impact of repeated annual community directed treatment with ivermectin on loiasis
      parasitological indicators in Cameroon: Implications for onchocerciasis and
      lymphatic filariasis elimination in areas co-endemic with Loa loa in Africa.
AB  - BACKGROUND: Loiasis is a filarial infection endemic in the rainforest zone of
      west and central Africa particularly in Cameroon, Gabon, Republic of Congo, and
      Democratic Republic of the Congo. Repeated treatments with ivermectin have been
      delivered using the annual community directed treatment with ivermectin (CDTI)
      approach for several years to control onchocerciasis in some Loa loa-Onchocerca
      volvulus co-endemic areas. The impact of CDTI on loiasis parasitological
      indicators is not known. We, therefore, designed this cross sectional study to
      explore the effects of several rounds of CDTI on parasitological indicators of
      loiasis. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in the East,
      Northwest and Southwest 2 CDTI projects of Cameroon. Individuals who consented to
      participate were interviewed for ivermectin treatment history and enrolled for
      parasitological screening using thick smears. Ivermectin treatment history was
      correlated with loiasis prevalence/intensity. A total of 3,684 individuals were
      recruited from 36 communities of the 3 CDTI projects and 900 individuals from 9
      villages in a non-CDTI district. In the East, loiasis prevalence was 29.3% (range
      = 24.2%-34.6%) in the non-CDTI district but 16.0% (3.3%-26.6%) in the CDTI
      district with 10 ivermectin rounds (there were no baseline data for the latter).
      In the Northwest and Southwest 2 districts, reductions from 30.5% to 17.9% (after
      9 ivermectin rounds) but from 8.1% to 7.8% (not significantly different after 14
      rounds) were registered post CDTI, respectively. Similar trends in infection
      intensity were observed in all sites. There was a negative relationship between
      adherence to ivermectin treatment and prevalence/intensity of infection in all
      sites. None of the children (aged 10-14 years) examined in the East CDTI project
      harboured high (8,000-30,000 mf/ml) or very high (>30,000 mf/ml) microfilarial
      loads. Individuals who had taken >5 ivermectin treatments were 2.1 times more
      likely to present with no microfilaraemia than those with less treatments.
      CONCLUSION: In areas where onchocerciasis and loiasis are co-endemic, CDTI
      reduces the number of, and microfilaraemia in L. loa-infected individuals, and
      this, in turn, will help to prevent non-neurological and neurological
      complications post-ivermectin treatment among CDTI adherents.

PMID- 30226901
TI  - Suppression of the synaptic localization of a subset of proteins including APP
      partially ameliorates phenotypes of the Drosophila Alzheimer's disease model.
AB  - APP (amyloid precursor protein), the causative molecule of Alzheimer's disease,
      is synthesized in neuronal cell bodies and subsequently transported to synapses.
      We previously showed that the yata gene is required for the synaptic transport of
      the APP orthologue in Drosophila melanogaster. In this study, we examined the
      effect of a reduction in yata expression in the Drosophila Alzheimer's disease
      model, in which expression of human mutant APP was induced. The synaptic
      localization of APP and other synaptic proteins was differentially inhibited by
      yata knockdown and null mutation. Expression of APP resulted in abnormal synaptic
      morphology and the premature death of animals. These phenotypes were partially
      but significantly rescued by yata knockdown, whereas yata knockdown itself caused
      no abnormality. Moreover, we observed that synaptic transmission accuracy was
      impaired in our model, and this phenotype was improved by yata knockdown. Thus,
      our data suggested that the phenotypes caused by APP can be partially prevented
      by inhibition of the synaptic localization of a subset of synaptic proteins
      including APP.

PMID- 30226902
TI  - Tree species richness predicted using a spatial environmental model including
      forest area and frost frequency, eastern USA.
AB  - Assessing geographic patterns of species richness is essential to develop
      biological conservation as well as to understand the processes that shape these
      patterns. We aim to improve geographic prediction of tree species richness (TSR)
      across eastern USA by using: 1) gridded point-sample data rather than spatially
      generalized range maps for the TSR outcome variable, 2) new predictor variables
      (forest area FA; mean frost day frequency MFDF) and 3) regression models that
      account for spatial autocorrelation. TSR was estimated in 50 km by 50 km grids
      using Forest Inventory and Analysis (FIA) point-sample data. Eighteen
      environmental predictor variables were employed, with the most effective set
      selected by a LASSO that reduced multicollinearity. Those predictors were then
      employed in Generalized linear models (GLMs), and in Eigenvector spatial
      filtering (ESF) models that accounted for spatial autocorrelation. Models were
      evaluated by model fit statistics, spatial patterns of TSR predictions, and
      spatial autocorrelation. Our results showed gridded TSR was best-predicted by the
      ESF model that used, in descending order of influence: precipitation seasonality,
      mean precipitation in the driest quarter, FA, and MFDF. ESF models, by accounting
      for spatial autocorrelation, outperformed GLMs regardless of the predictors
      employed, as indicated by percent deviance explained and spatial autocorrelation
      of residuals. Small regions with low TSR, such as the Midwest prairie peninsula,
      were successfully predicted by ESF models, but not by GLMs or other studies.
      Gridded TSR in Florida was only correctly predicted by the ESF model with FA and
      MFDF, and was over-predicted by all other models.

PMID- 30226903
TI  - Using wearable sensors to classify subject-specific running biomechanical gait
      patterns based on changes in environmental weather conditions.
AB  - Running-related overuse injuries can result from a combination of various
      intrinsic (e.g., gait biomechanics) and extrinsic (e.g., running surface) risk
      factors. However, it is unknown how changes in environmental weather conditions
      affect running gait biomechanical patterns since these data cannot be collected
      in a laboratory setting. Therefore, the purpose of this study was to develop a
      classification model based on subject-specific changes in biomechanical running
      patterns across two different environmental weather conditions using data
      obtained from wearable sensors in real-world environments. Running gait data were
      recorded during winter and spring sessions, with recorded average air
      temperatures of -10 degrees  C and +6 degrees  C, respectively. Classification
      was performed based on measurements of pelvic drop, ground contact time, braking,
      vertical oscillation of pelvis, pelvic rotation, and cadence obtained from 66,370
      strides (~11,000/runner) from a group of recreational runners. A non-linear and
      ensemble machine learning algorithm, random forest (RF), was used to classify and
      compute a heuristic for determining the importance of each variable in the
      prediction model. To validate the developed subject-specific model, two cross
      validation methods (one-against-another and partitioning datasets) were used to
      obtain experimental mean classification accuracies of 87.18% and 95.42%,
      respectively, indicating an excellent discriminatory ability of the RF-based
      model. Additionally, the ranked order of variable importance differed across the
      individual runners. The results from the RF-based machine-learning algorithm
      demonstrates that processing gait biomechanical signals from a single wearable
      sensor can successfully detect changes to an individual's running patterns based
      on data obtained in real-world environments.

PMID- 30226905
TI  - Correction: Mice Hemizygous for a Pathogenic Mitofusin-2 Allele Exhibit Hind
      Limb/Foot Gait Deficits and Phenotypic Perturbations in Nerve and Muscle.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0167573.].

PMID- 30226904
TI  - Host phosphatidic acid phosphatase lipin1 is rate limiting for functional
      hepatitis C virus replicase complex formation.
AB  - Hepatitis C virus (HCV) infection constitutes a significant health burden
      worldwide, because it is a major etiologic agent of chronic liver disease,
      cirrhosis and hepatocellular carcinoma. HCV replication cycle is closely tied to
      lipid metabolism and infection by this virus causes profound changes in host
      lipid homeostasis. We focused our attention on a phosphatidate phosphate (PAP)
      enzyme family (the lipin family), which mediate the conversion of phosphatidate
      to diacylglycerol in the cytoplasm, playing a key role in triglyceride
      biosynthesis and in phospholipid homeostasis. Lipins may also translocate to the
      nucleus to act as transcriptional regulators of genes involved in lipid
      metabolism. The best-characterized member of this family is lipin1, which
      cooperates with lipin2 to maintain glycerophospholipid homeostasis in the liver.
      Lipin1-deficient cell lines were generated by RNAi to study the role of this
      protein in different steps of HCV replication cycle. Using surrogate models that
      recapitulate different aspects of HCV infection, we concluded that lipin1 is rate
      limiting for the generation of functional replicase complexes, in a step
      downstream primary translation that leads to early HCV RNA replication. Infection
      studies in lipin1-deficient cells overexpressing wild type or phosphatase
      defective lipin1 proteins suggest that lipin1 phosphatase activity is required to
      support HCV infection. Finally, ultrastructural and biochemical analyses in
      replication-independent models suggest that lipin1 may facilitate the generation
      of the membranous compartment that contains functional HCV replicase complexes.

PMID- 30226907
TI  - Cardiovascular Diseases in Portuguese: The Importance of Preventive Medicine.

PMID- 30226906
TI  - Cardiovascular Disease Epidemiology in Portuguese-Speaking Countries: data from
      the Global Burden of Disease, 1990 to 2016.
AB  - BACKGROUND: Portuguese-speaking countries (PSC) share the influence of the
      Portuguese culture but have socioeconomic development patterns that differ from
      that of Portugal. OBJECTIVE: To describe trends in cardiovascular disease (CVD)
      morbidity and mortality in the PSC between 1990 and 2016, stratified by sex, and
      their association with the respective sociodemographic indexes (SDI). METHODS:
      This study used the Global Burden of Disease (GBD) 2016 data and methodology.
      Data collection followed international standards for death certification, through
      information systems on vital statistics and mortality surveillance, surveys, and
      hospital registries. Techniques were used to standardize causes of death by the
      direct method, as were corrections for underreporting of deaths and garbage
      codes. To determine the number of deaths due to each cause, the CODEm (Cause of
      Death Ensemble Model) algorithm was applied. Disability-adjusted life years
      (DALYs) and SDI (income per capita, educational attainment and total fertility
      rate) were estimated for each country. A p-value <0.05 was considered
      significant. RESULTS: There are large differences, mainly related to
      socioeconomic conditions, in the relative impact of CVD burden in PSC. Among CVD,
      ischemic heart disease was the leading cause of death in all PSC in 2016, except
      for Mozambique and Sao Tome and Principe, where cerebrovascular diseases have
      supplanted it. The most relevant attributable risk factors for CVD among all PSC
      are hypertension and dietary factors. CONCLUSION: Collaboration among PSC may
      allow successful experiences in combating CVD to be shared between those
      countries.

PMID- 30226909
TI  - Identifying the Impact of Metabolic Syndrome in Hypertensive Patients.

PMID- 30226908
TI  - Metabolic Syndrome-Related Features in Controlled and Resistant Hypertensive
      Subjects.
AB  - BACKGROUND: Metabolic syndrome (MetS) is widespread among hypertensive patients.
      Clinical features and potential biomarkers of MetS in the presence of
      hypertension and resistant hypertension (RHTN) represent a great area of interest
      for investigation. OBJECTIVE: The purpose of this study was to evaluate the
      prevalence of MetS and the clinical features associated with it in resistant and
      mild to moderate hypertensives. METHODS: This cross-sectional study included 236
      patients, (i) 129 mild to moderate hypertensive patients and (ii) 107 patients
      with RHTN. We measured blood pressure (BP) and adipokines levels, and performed
      bioelectrical impedance analysis. Microalbuminuria (MA), cardiac hypertrophy and
      arterial stiffness were also assessed. The significance level of alpha = 0.05 was
      adopted. RESULTS: We found a MetS prevalence of 73% in resistant and 60% in mild
      to-moderate hypertensive patients. In a multiple regression analysis, MA (odds
      ratio = 8.51; p = 0.01), leptin/adiponectin ratio (LAR) (odds ratio = 4.13; p =
      0.01) and RHTN (odds ratio = 3.75; p = 0.03) were independently associated with
      the presence of MetS apart from potential confounders. CONCLUSIONS: Our findings
      suggest that both resistant and controlled hypertensive subjects have a high
      prevalence of MetS. In addition, MetS-related metabolic derangements may cause
      early renal and hormonal changes. Finally, LAR may be useful as a reliable
      biomarker for identifying those hypertensive subjects who are at risk for
      developing MetS.

PMID- 30226910
TI  - Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: What has
      Changed in The Guidelines?
AB  - BACKGROUND: The new European Society of Cardiology guidelines for hypertrophic
      cardiomyopathy (HCM) define the estimation of sudden cardiac death (SCD) risk as
      an integral part of clinical management. An implantable cardioverter
      defibrillator (ICD) is recommended (class IIa) when the risk is >= 6%.
      OBJECTIVES: To compare the SCD risk stratification according to the 2011 and 2014
      recommendations for ICD implantation in patients with HCM. METHODS: Retrospective
      study including 105 patients diagnosed with HCM. The indication for ICD was
      assessed using the 2011 and 2014 guidelines. Statistical analysis was performed
      using SPSS software version 19.0.0.2(r). The tests performed were bilateral,
      considering the significance level of 5% (p < 0.05). RESULTS: Regarding primary
      prevention, according to the 2011 ACCF/AHA recommendations, 39.0% of the patients
      had indication for ICD implantation (level of evidence IIa). Using the 2014
      guidelines, only 12.4% of the patients had an indication for ICD implantation.
      Comparing the two risk stratification models for patients with HCM, we detected a
      significant reduction in the number of indications for ICD implantation (p <
      0.001). Of the 41 patients classified as IIa according to the 2011
      recommendations, 68.3% received a different classification according to the 2014
      guidelines. CONCLUSION: Significant differences were found when comparing the SCD
      risk stratification for ICD implantation in the two guidelines. The current SCD
      risk score seems to identify many low-risk patients who are not candidates for
      ICD implantation. The use of this new score results in a significant reduction in
      the number of ICD implanted.

PMID- 30226911
TI  - Prevention of Sudden Death in Hypertrophic Cardiomyopathy.

PMID- 30226912
TI  - Is There any Relationship Between Myocardial Repolarization Parameters and the
      Frequency of Ventricular Premature Contractions?
AB  - BACKGROUND: Ventricular premature contractions (VPCs) may trigger lethal
      ventricular arrhythmias in patients with structural heart disease. However, this
      role of VPCs in healthy people remains controversial once that not enough
      clinical trials are available. Recently, some myocardial repolarization markers,
      such as Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios, have been reported to be
      useful for predicting lethal ventricular arrhythmias in various clinical
      disorders without structural heart disease. OBJECTIVE: In this study, we aimed to
      investigate the relation between VPC frequent and myocardial repolarization
      markers in individuals without structural heart disease. METHODS: This study
      included 100 patients who had complaints of dizziness and palpitations. Twelve
      lead electrocardiography and 24-hour ambulatory Holter recordings were obtained
      from all patients. VPC burden was calculated as the total number of VPCs divided
      by the number of all QRS complexes in the total recording time. P-values < 0.05
      were considered significant. RESULTS: Tp-e interval and Tp-e/QTc ratio were
      significantly higher in patients with higher VPC burden than in patients with
      lower VPC burden, and a positive correlation was found between these markers and
      VPC burden. Tp-e (beta = 1.318, p = 0.043) and Tp-e/QTc (beta = -405.136, p =
      0.024) in the lead V5 were identified as independent predictors of increased VPC
      burden. CONCLUSIONS: Tp-e interval and Tp-e/QTc ratio increased in patients with
      high VPC number. Our study showed that VPCs may have a negative effect on
      myocardial repolarization. This interaction may lead to an increased risk of
      malignant arrhythmias.

PMID- 30226913
TI  - Cardiovascular Risk in Xavante Indigenous Population.
AB  - BACKGROUND: The prevalence of cardiovascular risk factors is little known in
      Brazilian indigenous populations. In the last two decades, important changes have
      occurred in the lifestyle and epidemiological profile of the Xavante people.
      OBJECTIVE: to assess the prevalence of cardiovascular risk factors in Xavante
      adults in Sao Marcos and Sangradouro/Volta Grande reserves, in the state of Mato
      Grosso, Brazil. METHODS: Cross-sectional study carried out with 925 Xavante
      people aged >= 20 years between 2008 and 2012. The following indicators were
      assessed: triglycerides (TG), total, LDL and HDL-cholesterol, Castelli index I
      and II, TG/HDL-cholesterol ratio, apo B / Apo A1 ratio, Framingham risk score, C
      reactive protein, body mass index (BMI), waist circumference (WC),
      hypertriglyceridemic waist (HW), glycemia and blood pressure. Kolmogorov-Smirnov,
      Student's t test and Chi-square test (chi2) were used for statistical analysis,
      and significance level was set at 5%. RESULTS: High prevalence of elevated
      cardiovascular risk was observed in men and women according to HDL-cholesterol
      (66.2% and 86.2%, respectively), TG (53.2% and 51.5%), TG/HDL-cholesterol ratio
      (60.0% and 49.1%), C-reactive protein (44.1% and 48.1%), BMI (81.3% and 81.7%),
      WC (59.1% and 96.2%), HW (38.0% and 50,6%) and glycemia (46.8% and 70.2%).
      Individuals aged 40 to 59 years had the highest cardiovascular risk. CONCLUSIONS:
      The Xavante have a high cardiovascular risk according to several indicators
      evaluated. The present analysis of cardiovascular risk factors provides support
      for the development of preventive measures and early treatment, in attempt to
      minimize the impact of cardiovascular diseases on this population.

PMID- 30226914
TI  - Behavior of Blood Pressure Variables in Children and Adolescents with Duchenne
      Muscular Dystrophy.
AB  - BACKGROUND: Duchenne muscular dystrophy is an X-chromosome-linked genetic
      disorder (locus Xp21). Involvement of the cardiovascular system is characterized
      by fibrous degeneration/replacement of myocytes with consequent ventricular
      hypertrophy and arterial hypertension. OBJECTIVE: To assess, by using 24-hour
      ambulatory blood pressure monitoring, the behavior of blood pressure variables in
      children and adolescents with a confirmed diagnosis of Duchenne muscular
      dystrophy. METHODS: Prospective observational cohort study, which selected 46
      patients followed up on an outpatient basis, divided according to age groups.
      Blood pressure was classified according to the age percentile. The monitoring
      interpretation includes systolic and diastolic blood pressure means, systolic and
      diastolic blood pressure loads, and nocturnal dipping. The blood pressure means
      were calculated for the 24-hour, wakefulness and sleep periods. Nocturnal dipping
      was defined as a drop in blood pressure means during sleep greater than 10%. The
      significance level adopted was p < 0.05. RESULTS: Nocturnal dipping for systolic
      blood pressure was present in 29.9% of the participants. Approximately 53% of
      them had attenuated nocturnal dipping, and 15%, reverse nocturnal dipping. The
      age groups of 9-11 years and 6-8 years had the greatest percentage of
      attenuation, 19.1% and 14.9%, respectively. Regarding diastolic blood pressure,
      nocturnal dipping was identified in 53.2% of the children, being extreme in 27.7%
      of those in the age group of 6-11 years. CONCLUSIONS: The early diagnosis of
      blood pressure changes can allow the appropriate and specific therapy, aimed at
      increasing the life expectancy of patients with Duchenne muscular dystrophy.

PMID- 30226915
TI  - Endothelial Dysfunction and Inflammation Precedes Elevations in Blood Pressure
      Induced by a High-Fat Diet.
AB  - BACKGROUND: Obesity leads to a chronic inflammatory state, endothelial
      dysfunction and hypertension. OBJECTIVE: To establish the time-course of events
      regarding inflammatory markers, endothelial dysfunction, systolic blood pressure
      (SBP) in obesity in only one experimental model. METHODS: We fed male Wistar rats
      (eight-week age) with a standard diet (Control - CT, n = 35), or palatable high
      fat diet (HFD, n = 35) for 24 weeks. Every six weeks, 7 animals from each group
      were randomly selected for euthanasia. SBP and serum levels of interleukin-6,
      tumor necrosis factor-alpha, C-reactive protein, adiponectin and nitric oxide
      were determined. Endothelial and vascular smooth muscle functions were determined
      in dissected aorta and lipid peroxidation was measured. Statistical significance
      was set at p < 0.05. RESULTS: Levels of pro-inflammatory cytokines began to
      increase after six weeks of a high-fat diet, while those of the anti-inflammatory
      cytokine adiponectin decreased. Interestingly, the endothelial function and serum
      nitric oxide began to decrease after six weeks in HFD group. The SBP and lipid
      peroxidation began to increase at 12 weeks in HFD group. In addition, we showed
      that total visceral fat mass was negatively correlated with endothelial function
      and positively correlated with SBP. CONCLUSION: Our results show the time-course
      of deleterious effects and their correlation with obesity.

PMID- 30226916
TI  - Pressure Overload-induced Cardiac Hypertrophy Varies According to Different
      Ligation Needle Sizes and Body Weights in Mice.
AB  - BACKGROUND: The cardiac hypertrophy (CH) model for mice has been widely used,
      thereby providing an effective research foundation for CH exploration. OBJECTIVE:
      To research the effects of CH modeling under abdominal aortic constriction (AAC)
      using different needles and weights in mice. METHODS: Four needles with different
      external diameters (0.35, 0.40, 0.45, and 0.50 mm) were used for AAC. 150 male
      C57BL/6 mice were selected according to body weight (BW) and divided into 3
      weight levels: 18 g, 22 g, and 26 g (n = 50 in each group). All weight levels
      were divided into 5 groups: a sham group (n = 10) and 4 AAC groups using 4
      ligation intensities (n = 10 per group). After surgery, survival rates were
      recorded, echocardiography was performed, hearts were dissected and used for
      histological detection, and data were statistically analyzed, P < 0.05 was
      considered statistically significant. RESULTS: All mice died in the following AAC
      groups: 18g/0.35 mm, 22 g/0.35 mm, 26 g/0.35 mm, 22 g/0.40 mm, and 26 g/0.40 mm.
      All mice with AAC, those ligated with a 0.50-mm needle, and those that underwent
      sham operation survived. Different death rates occurred in the following AAC
      groups: 18 g/0.40 mm, 18 g/0.45 mm, 18 g/0.50 mm, 22 g/45 mm, 22 g/0.50 mm, 26
      g/0.45 mm, and 26 g/0.50 mm. The heart weight/body weight ratios (5.39 +/- 0.85,
      6.41 +/- 0.68, 4.67 +/- 0.37, 5.22 +/- 0.42, 4.23 +/- 0.28, 5.41 +/- 0.14, and
      4.02 +/- 0.13) were significantly increased compared with those of the sham
      groups for mice with the same weight levels. CONCLUSION: A 0.45-mm needle led to
      more obvious CH than did 0.40-mm and 0.50-mm needles and caused extraordinary CH
      in 18-g mice.

PMID- 30226917
TI  - Pulmonary Ultrasound in Patients with Heart Failure - Systematic Review.
AB  - Pulmonary congestion is an important clinical finding in patients with heart
      failure (HF). Physical examination and chest X-ray have limited accuracy in
      detecting congestion. Pulmonary ultrasound (PU) has been incorporated into
      clinical practice in the evaluation of pulmonary congestion. This paper aimed to
      perform a systematic review of the use of PU in patients with HF, in different
      scenarios. A search was performed in the MEDLINE and LILACS databases in February
      2017 involving articles published between 2006 and 2016. We found 26 articles in
      the present review, 11 of which in the emergency setting and 7 in the outpatient
      setting, with diagnostic and prognosis defined value and poorly studied
      therapeutic value. PU increased accuracy by 90% as compared to physical
      examination and chest X-ray for the diagnosis of congestion, being more sensitive
      and precocious. The skill of the PU performer did not interfere with diagnostic
      accuracy. The presence of B-lines >= 15 correlated with high BNP values (>= 500)
      and E/e' ratio >= 15, with prognostic impact in IC patients at hospital discharge
      and those followed up on an outpatient basis. In conclusion, when assessing
      pulmonary congestion in HF, PU has an incremental value in the diagnostic and
      prognostic approach in all scenarios studied.

PMID- 30226918
TI  - Update of the Impact of Consumption of Whole Chicken Eggs on the Lipid Profile:
      to What Extent are They Impacting?

PMID- 30226919
TI  - Case 3/2018 - A 60-year-old Female with Chagasic Heart Disease, Admitted Due to
      Heart Failure Decompensation, Cachexia and Pulmonary Infection.

PMID- 30226920
TI  - Eosinophilic Myocarditis: Clinical Case and Literature Review.

PMID- 30226921
TI  - Challenging Diagnosis of Myocardial Infarction Due to Anomalous Left Circumflex
      Artery.

PMID- 30226922
TI  - QTc and QTcd Measurements and Their Relationships with Left Ventricular
      Hypertrophy in Hemodialysis PatientsReplyMedidas de QTc e QTcd e suas Relacoes
      com Hipertrofia Ventricular Esquerda em Pacientes em Hemodialise.

PMID- 30226923
TI  - Why different water models predict different structures under 2D confinement.
AB  - Experiments of nanoconfined water between graphene sheets at high pressure
      suggest that it forms a square ice structure (Algara-Siller et al., Nature, 2015,
      519, 443). Molecular dynamics (MD) simulations have been used to attempt to
      recreate this structure, but there have been discrepancies in the structure
      formed by the confined water depending on the simulation set-up that was employed
      and particularly on the choice of water model. Here, using classical molecular
      dynamics simulations, we have systematically investigated the effect that three
      different water models (SPC/E, TIP4P/2005 and TIP5P) have on the structure of
      water confined between two rigid graphene sheets with a 0.9 nm separation. We
      show that the TIP4P/2005 and the TIP5P water models form a hexagonal AA-stacked
      structure, whereas the SPC/E model forms a rhombic AB-stacked structure. Our work
      demonstrates that the formation of these structures is driven by differences in
      the strength of hydrogen bonds predicted by the three water models, and that the
      nature of the graphene/water interaction only mildly affects the phase diagram.
      Considering the available experimental data and first-principle simulations we
      conclude that, among the models tested, the TIP4P/2005 and TIP5P force fields are
      for now the most reliable when simulating water under confinement. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30226924
TI  - Maximal orbital analysis of molecular wavefunctions.
AB  - We describe a new way to decompose one-electron orbitals of a molecule into atom
      centered or fragment-centered orbitals by an approach that we call "maximal
      orbital analysis" (MOA). The MOA analysis is based on the corresponding orbital
      transformation (COT) that has the unique mathematical property of maximizing any
      sub-trace of the overlap matrix, in Hilbert metric sense, between two sets of
      nonorthogonal orbitals. Here, one set comprises the molecule orbitals (Hartree
      Fock, Kohn-Sham, complete-active-space, or any set of orthonormal molecular
      orbitals), the other set comprises the basis functions associated with an atom or
      a group of atoms. We show in prototypical molecular systems such as a water
      dimer, metal carbonyl complexes, and a mixed-valent transition metal complex,
      that the MOA orbitals capture very well key aspects of wavefunctions and the
      ensuing chemical concepts that govern electronic interactions in molecules. (c)
      2019 Wiley Periodicals, Inc.

PMID- 30226925
TI  - Putting placebo-controlled trials in developing countries to the interpersonal
      justifiability test.
AB  - This paper considers the ethics of placebo-controlled trials in developing
      countries, where a treatment already exists but is not available due to the low
      local standard of care. Such trials would not be permitted in more developed
      nations where a higher standard of care is available. I argue that there are
      moral intuitions against such trials, but a further intuition that if the trials
      were aimed at producing treatment options for the developing world, that would be
      more permissible than if the trials were designed with the benefit of rich world
      people in mind. An approach based upon GA Cohen's work on interpersonal
      justifiability is suggested to allow us to explain these intuitions. Cohen's
      framework shows that these trials are ethically problematic because the
      inequality in healthcare provision between developing and developed nations that
      allows them to take place is at least partly the pharmaceutical corporations'
      fault. Following Cohen's argument, this means the trials are non-comprehensively
      justified. This allows for a more complete explanation of our intuitions than to
      consider such trials as cases of exploitation, because intuitions on the ethicacy
      of research can vary even when the exploitation relation remains the same. It is
      then established that there is good empirical evidence to believe that
      pharmaceutical corporations do fail the interpersonal justifiability test. The
      policy implications of this judgement are then considered, and it is suggested
      that the framework might be equally applicable to examining the permissibility of
      research conducted on vulnerable people within more developed nations.

PMID- 30226927
TI  - Corrigendum.

PMID- 30226926
TI  - Genomics, bio specimens, and other biological data: Current status and future
      directions.

PMID- 30226928
TI  - New salicylic acid and pyroglutamic acid conjugated derivatives confer protection
      to bread wheat against Zymoseptoria tritici.
AB  - BACKGROUND: To promote sustainable agriculture and healthy food, research that
      contributes towards a new generation of eco-friendly phytosanitary compounds is
      increasingly encouraged. The plant hormone salicylic acid (SA) is known for its
      ability to induce resistance in plants against a wide range of pathogens, whereas
      pyroglutamic acid (PGA), a constrained analogue of gamma-aminobutyric acid, has
      never been studied in the context of plant protection. RESULTS: The present study
      investigated for the first time the protection efficacy of SA and PGA and five
      new conjugated derivatives against Zymoseptoria tritici, the main pathogen in
      wheat crops. SA and four derivatives showed significant disease severity
      reductions in planta (up to 49%). In vitro assays revealed that some molecules,
      including SA, displayed a small direct antifungal activity, whereas others, such
      as PGA, showed no effect. This finding suggests that, especially for molecules
      without any direct activity, the mode of action relies mainly on the induction of
      plant resistance. CONCLUSION: Further investigations are needed to identify the
      defence pathways involved in plant resistance mechanisms elicited or primed by
      the molecules. The manufacture of these products was easily achieved on a scale
      of tens of grams of raw materials, and is easily scalable. The synthetic pathway
      is simple, short and inexpensive. For all of these reasons, the production of the
      target molecules is attractive for producers, whereas the prospect of a
      generation of non-polluting compounds with lasting efficiency against Z. tritici
      in wheat comes at a key moment for the sustainability of agriculture. (c) 2018
      Society of Chemical Industry.

PMID- 30226929
TI  - Importance of prevention in pneumonia in elderly -Attempted use of macrolide
      therapy.
AB  - Pneumonia ranks as the third leading cause of death in Japan. About 97% of
      patients who die because of pneumonia are elderly, with aspiration generally
      thought to be involved in the majority of cases of pneumonia in elderly. Once an
      elderly individual contracts pneumonia, their physical function often declines
      and their activities of daily living diminish with hospital admission, even in
      individuals with no underlying disorders. Prolonged confinement to a bed and
      immobility leads to weakening of the legs and back, making it difficult for
      elderly patients to attend daily outpatient clinics, often leading to admission
      to nursing facilities for the aged instead of returning to their own home, even
      after curative treatment for pneumonia. Most such patients repeatedly develop
      pneumonia and repeated antibiotic treatment enhances the risk of the emergence of
      resistant organisms. It is beyond doubt, therefore, that prevention of pneumonia
      is of vital importance in the elderly.

PMID- 30226930
TI  - High efficiency method of detection and isolation of neuraminidase inhibitor
      resistant influenza viruses by fluorescence sialidase imaging.
AB  - Influenza A and B viruses possess an enzyme "sialidase" that cleavages terminal
      sialic acid from glycochains. These viral sialidase proteins are highly expressed
      on the virus infected cells. We developed sialidase imaging probe "BTP3-Neu5Ac"
      that enables histochemical fluorescence staining of sialidase activity. BTP3
      Neu5Ac was able to perform speedy and easy fluorescence imaging of these virus
      infected cells, with no needs of specific antibody and cell fixation. In
      addition, combination use of anti-influenza drugs (sialidase inhibitors) and BTP3
      Neu5Ac resulted in selective fluorescence imaging for detection and high
      efficiency isolation of drug-resistant virus. Fluorescence imaging of drug
      resistant virus will be a powerful method for study of the drug-resistance
      mechanism, for monitoring of drug-resistant viruses. A novel tool for
      fluorescence imaging of viral sialidase activity is described in this review.

PMID- 30226931
TI  - The change of susceptibility of Streptococcus pneumoniae strains isolated from
      pediatric patients at Asahikawa Kosei Hospital between 2011 and 2015.
AB  - The susceptibility of 1578 Streptococcus pneumoniae strains isolated from
      pediatric patients at Asahikawa Kosei Hospital between 2011 and 2015 was tested
      to penicillin G (PCG), cefotaxime (CTX), ceftriaxone (CTRX), cefditoren (CDTR),
      meropenem (MEPM), erythromycin (EM) and levofloxacin (LVFX). Although no
      significant differences were observed, the percentage of strains with a minimal
      inhibitory concentration (MIC) of PCG of <0.1pg/mL increased from 55.5% (2011) to
      64.0% (2015), whereas that of strains with MIC of >=2MUg/mL decreased from 14.8%
      to 9.5%. From 2011 to 2015, the percentage of strains with MIC <=0.12ug/mL
      increased from 18.9% to 28.9% for CTX, from 20.5% to 30.2% for CTRX, from 29.2%
      to 40.9% for CDTR, and from 69.6% to 80.6% for MEPM. EM-resistant strains with
      MIC >=22MUg/mL accounted for as much as approximately 90% each year. One LVFX
      resistant strain with MIC 8pg/mL has been detected each year since 2013.

PMID- 30226932
TI  - The Role of Protein Oxidative Modification and the Cellular Redox Status in
      Realization of Apoptosis of MCF-7 Breast Adenocarcmoma Cells.
AB  - The aim of this study was to establish the role of redox modification of proteins
      and redox status in the realization of apoptosis of MCF-7 breast adenocarcinoma
      cells du-ing cultivation with the SH-group blocker N-ethylmaleimide (NEM) and the
      SH-group protector 1,4-dithioerythritol (DTE). The activation of apoptosis in MCF
      7 breast adenocarcinoma cells was shown to be due to the irreversible
      modification of redox sensitive protein molecules. The presence of DTE in the
      culture medium of cancer.cells caused reversible glutathionylation of protein
      molecules and did not change the: number of apoptotic MCF-7 cells.

PMID- 30226933
TI  - Functional Diversity of Ant-Associated Bacterial Communities.
AB  - It was found that ants significantly affect the physiological activity and
      functional diversity of soil microbial communities, and redistribution of
      biophilic elements (C and N) down through the profile occurs in anthills compared
      to the control soil, as well as their accumulation in the underground part of the
      ant nests. A high urease activity was revealed in ant nests and ants. Functional
      dissimilarities of bacterial communities in all studied objects were determined
      by the miultisubstrate test.

PMID- 30226934
TI  - Molecular Phylogeny of Monoraphid Diatoms and Raphe Significance in Evolution and
      Taxonomy.
AB  - The phylogenetic position of the genera Rossithidium and Psammothidium was
      studied using the plastid gene rbcL. The genus Rossithidium is not an independent
      taxon and should be transferred to Psammothidium. Taxa from Psammothidium genus
      formed a sister, but independent clade to taxa with Achnanthidium. Our data has
      shown that the order Achnathales was not the natural taxon and should be reduced,
      but the three families included in it were natural. Genera like Psammothidium
      (including Rossithidium) and Lemnicola should be included into the family
      Achnanthidiaceae. Therefore, raphe does not play an important role in diatom
      taxonomy and its loss occurred many times during the evolution of diatoms.

PMID- 30226935
TI  - Lichen Symbiosis: Search and Recognition of Partners.
AB  - The problems associated with the initial stages of the formation of the thallus
      of lichens, i.e., compatibility of symbiotic partners, recognition ofsymbionts,
      and signals required for the formation of the differentiated thallus, are
      discussed.

PMID- 30226937
TI  - Ontogenetic Intraspecific Allometry of Autochthonous and Reintroduced Eurasian
      Beaver Castor fiber Populations.
AB  - Ontogenetic allometry.of the cranium was studied in 580 individuals of the
      Eurasian beavers Castorfiber in two subspecies out of six autochthonous and
      reintroduced populations using the methods of multivariate nonparametric
      statistics. It was noted that the growth dynamics demonstrates a correspondence
      to trajectories of ontogenetic rodent models with the difference that intensive
      beaver growth finishes by the age of four years. Significant differences in the
      dynamics ofage variability were detected in the beavers of two subspecies; with
      somewhat smaller initial postnatal sizes, C.fiber belorussicus grows faster than
      C.fiber orientoeuropaeus.

PMID- 30226936
TI  - Effects of Exogenous H202 on the Content of Endogenous H202, Activities of
      Catalase and Hydrolases, and Cell Ultrastructure in Tobacco Leaves.
AB  - It was shown that tobacco leaf treatment with 100 mM H202 increased their content
      ofendogenous H202 and activities of catalase and hydrolases (acid phosphatase,
      proteases, and RNase) and also caused'various chang- es in the cell structure. In
      this case, programmed cell death (PCD) occurred in some cells, which was ob-
      served as chromatin condensation, cytoplasm collapse, etc. In the meantime, many
      cells displayed organelle activation rather than PCD. It is suggested that cells
      that undergo H202-dependent PCD release signaling molecules inducing protective
      mechanisms against oxidative stress in neighboring cells not exhibiting PCD.

PMID- 30226938
TI  - Morphometric Distances and Population Structuring in the Common Shrew Sorex
      araneus L. (Lipotyphla: Soricidae).
AB  - The skulls of shrews of genus Sorex from eight samplings from the European part
      of Russia and two from the vicinity of Novosibirsk were compared. The
      characteristics were identified using 22 marks on the axial skull. It was found
      that the centroid size differs significantly in the common and Laxmann's shrews
      S. caecutens and the pygmy shrew S. minutus, while for selected marks, the common
      and Laxmann's, as well as pygmy, shrews were significantly different in form, but
      the differences were very small between Laxmann's and pygmy shrews. The
      characteristic features of the biology of the shrews Sorex are discussed, which
      may contribute to understanding the general laws of the morphological evolution
      of the genus.

PMID- 30226939
TI  - Features of the Effect of a Complex Probiotic with Bacillus Bacteria and the
      Larvae of Hermetia illucens Biomass on Mozambique Tilapia (Oreochromis
      mossambicus O. niloticus) and Russian Sturgeon (Acipenser gueldenstaedti) Fry.
AB  - A study of the effect of a complex probiotic preparation with bacteria of the
      genus Bacillus and a microdose of larvae of the fly Hermetia illucens on the
      physiological. parameters of fish has been carried out. It was established that
      introduction of the complex into artificial feeds for tilapia and Russian
      sturgeon juveniles during their incubation in recirculating aquaculture systems
      improves the digestion efficiency and increases the rate of fish growth and body
      mass accumulation. In tilapia, a decrease in the cholesterol level was revealed,
      while in sturgeon, an increase in the hemoglobin content was found. It was noted
      that a probiotic with biologically active agents H. illucens had a stimulating
      effect on the development of sexual gonads in female sturgeon fry, promoted an
      increase in the ovary mass, and provided for the development of eggs without
      morphological disturbances.

PMID- 30226940
TI  - Microbial Population of the Digestive Tract of Click Beetle Larvae (Elateridae,
      Coleoptera).
AB  - The composition and functional structure of the intestinal microflora of three
      wireworm species (Agriotes obscurus (L.), Selatosomus aeneus (L.), and Ampedus
      pomorum (Herbst)) with different dietary regimes were studied. The total
      abundance of the microorganisms was evaluated by fluorescent microscopy, the
      group composition was assessed by inoculation on a solid glucose-peptone-yeast
      medium, and the functional diversity was estimated by multisubstrate testing. It
      was noted that, in the intestine of the larvae, the total number of
      microorganisms was lower by 1-2 orders of magnitude than in the soil and decaying
      wood. It was found that the composition of the intestinal microbial communities
      of wireworms was radically different from that of the substrate: the Bray-Curtis
      coefficient did not exceed 0.25. It was found that native forms accounted for
      more than half of the total number of saprotrophic bacteria: in the larvae, gram
      positive cocci, enterobacteria, Vibrionaceae, Acinetobacter, and some genera of
      coryneform bacteria, which were absent in the soil and wood, prevailed. The
      micromycetes were either absent (Agriotes) or were found in insignificant
      quantities (Selatosomus, Ampedus). In Selatosomus, apart from the intestinal
      forms, representatives of Mezorhizobium, No- cardioides, and Erwinia, occurring
      on plant substrates, were observed.

PMID- 30226941
TI  - Biomorphology of Actaea erythrocarpa Fisch. Individuals and Ecological
      Demographic Characterization of Its Cenopopulations.
AB  - The ecotopes of Actaea erythrocarpa Fisch. cenopopulations are. characterized
      according to five of Tsyga- nov's scales using bioindication methods. The
      morphological..polyvariation of vegetative organs appears as elongation of the A.
      erythrocarpa shoot fietameric units under different ecological conditions. As has
      been shown, the biometric characteristics ofA. erythrocarpa individuals depend on
      the ontogenetic state and habitat.

PMID- 30226942
TI  - Features of Soil Nematode Communities in Various Types of Natural Biocenoses:
      Informativeness of Assessment Parameters.
AB  - The association of different characteristics of soil nematode communities with
      the type of natural (forest and meadow) biocenoses and the main parameters of
      assessment of the state of soil ecosystems were determined in the course of
      monitoring. It was found that the number of nematodes and number of taxa in the
      fauna are highly variable. It was noted that meadow biocenoses stand apart by the
      diversity of nematodes and the proportion of phytoparasites in the community
      structure. A significant functional load in the distinguishing of the main types
      of biocenoses was determined only for the index reflecting the organic matter
      decomposition in the soil using discriminant analysis. It was shown that the
      complex analysis of the parameters of nematode communities most informatively
      characterizes the state of the soil ecosystem.

PMID- 30226943
TI  - Advantage and issue of silkworm model for development of anti-infective agents.
AB  - We established silkworm infection model for developing a novel antibiotic.
      Silkworm model has less ethical issues and is low cost compared to mammalian
      model, thus allow us to use a lot of individuals for screening assay. In
      addition, we can evaluate therapeutic activity and toxicity of candidate samples
      because silkworm has similar pharmacokinetics as mammals. Using this system, we
      identified a novel antibiotic named "Lysocin E". In this review article, we
      describe advantages of silkworm model for development of antimicrobial agents.

PMID- 30226944
TI  - Bactericidal effect of tosufloxacin on Haemophilus influenzae internalized in
      cultured human cells.
AB  - Nontypeable Haemophilus influenzae, one of the major causative bacteria for acute
      otitis media (AOM), is also considered to cause intractable otitis media
      including prolonged AOM and recurrent AOM in children by the mechanism of
      internalization of the bacteria into epithelial cells of middle ear mucosa. In
      this study, we visualized the dynamics of H. infiuenzae internalization in
      cultured human cells. We also examined the effects of antimicrobials, including a
      novel quinolone, tosufloxacin, and a cephem antibacterial agent, cefditoren, on
      H. influenzae internalized in cultured human cells. The results indicated that
      (1) H. infiuenzae were internalized into human cells, (2) cefditoren has no
      effect on internalized H. influenzae, and (3) tosufloxacin has a bactericidal
      action on H. infiuenzae invading human cells. These data strongly support high
      clinical efficacy of tosuffoxacin on intractable otitis media in children.

PMID- 30226945
TI  - Clinical experience with colistin in 9 Japanese patients with infection due to
      multi-drug resistance pathogens.
AB  - Colistin is a polypeptide antibiotic of the polymyxin family (polymyxin E) which
      has been reported to be active against many multidrug-resistant (MDR) Gram
      negative aerobic bacteria collected across the globe. While this agent was not
      currently licensed in Japan, the emergence of MDR organisms has necessitated its
      off-label used in the country. However, colistin was approved in March, 2015.
      This retrospective observational report includes nine patients with MDR Gram
      negative infections due to Pseudomonas aeruginosa (n=6) and Klebsiella spp. (n=3)
      who received intravenous colistin therapy as part of their antimicrobial regimen.
      The median age and duration of administration were 40 years (range 7-90) and 8
      days (range 1-19). Clinical success was observed in all eight patients for whom
      efficacy could be evaluated. Two patients encountered colistin related adverse
      effects 22.2% (2/9). In both cases the nephrotoxicity and dysgeusia resolved
      after discontinuation of colistin therapy. In vitro studies conducted with these
      clinical isolates of P aeruginosa displayed synergy with the combination of
      colistin plus ceftazidime, rifampicin, meropenem or aztreonam. This report
      provides early evidence that colistin is generally safe, effective and
      demonstrates in vitro synergy when used in combination for the management of MDR
      Gram-negative pathogens derived from Japanese patients.

PMID- 30226946
TI  - Sensitivity surveillance of Pseudomonas aeruginosa isolates for several
      antibacterial agents in Chubu area (2013-2014).
AB  - We investigated the susceptibility to antibacterial agents of 186 clinical
      isolates of Pseudomonas aeruginosa isolated from medical facilities in Gifu,
      Aichi, Toyama, and Fukui prefectures from October 2013 to February 2014. MIC50/90
      of piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ),
      cefepime (CFPM), imipenem (IPM), meropenem (MEPM), doripenem (DRPM), aztreonam
      (AZT), ciprofloxacin (CPFX), levofloxacin (LVFX), amikacin (AMK) and colistin
      (CL) against P aeruginosa was 8/32, 4/32, 2/8, 2/16, 1/32, 0.5/8, 0.25/4, 8/32,
      0.25/8, 0.5/16, 4/8 and 1/1pg/mLrespectively. Two strains of multidrug resistant
      P aeruginosa were isolated (1.1%). They were isolated from the respiratory tract,
      intra-abdominal, and urinary infection. The susceptible ratio against P
      aeruginosa derived from intra-abdominal infection for carbapenem was lower than
      those from respiratory tract and urinary infection. The susceptible ratio against
      P aeruginosa derived from urinary infection for penicillin, cephem, monobactam,
      and fluoroquinolone was lower than those from respiratory and intra-abdominal
      infection. It is meaningful to pay attention to the susceptibility to
      antibacterial agents in each clinical specimen from infected organ.

PMID- 30226947
TI  - A case of pediatric patient with acute enteritis due to CTX-M-1 5 extended
      spectrum beta-lactamase-producing Salmonella Blockley.
AB  - This clinical case report concerns a pediatric patient with acute enteritis
      caused by multi-drug resistant Salmonella enterica serovar Blockley (Salmonella
      Blockley). A 3-year-old boy presented to our emergency room with a 5-day history
      of fever, abdominal pain, and bloody diarrhea. Stool culture tested positive for
      a Salmonella species, while the blood culture was negative. The patient was
      successfully treated with an oral antibiotic regimen of fosfomycin. The stool
      isolate was found to be resistant to multiple drugs, including cefpodoxime,
      cefotaxime, ceftazidime, and aztreonam, and was confirmed to be a CTX-M-15
      extended-spectrum beta-lactamase (ESBL)-producing strain of Salmonella Blockley.
      This is the first report of a pediatric patient in Japan with acute enteritis
      caused by a CTX-M-15 ESBL- producing strain of Salmonella Blockley.

PMID- 30226948
TI  - Clinical evaluation of 3-day tebipenem pivoxil therapy in children with community
      acquired pneumonia.
AB  - A 4mg/kg dose of tebipenem pivoxil (TBPM-PI) was administered twice daily for 3
      days to 34 pediatric patients with pneumonia who had chest X-ray findings
      indicative of pneumonia and CRP values of at least 3.0 mg/dL. The clinical
      effects of this regimen were evaluated by retrospectively examining medical
      charts for the period from April 2012 to March 2015. The patients were 6 months
      to 8 years old, with serum CRP values ranging from 3.06 to 14.25 mg/dL. Fever
      resolved within 24 hours and respiratory symptoms improved within 3 to 5 days
      after the start of treatment in all 34 patients. Although CRP was positive in 28
      of 30 patients at the end of the treatment period, none of these children showed
      worsening of pneumonia. Eight patients (23.5%) experienced adverse drug reactions
      including diarrhea. These results indicate that a 3-day course of TBPM-PI is
      useful for treating pediatric pneumonia.

PMID- 30226949
TI  - In vitro activity of sitafloxacin against atypical bacteria (2009-2014) and
      comparison between susceptibility of clinical isolates in 2009 and 2012.
AB  - In vitro activities of sitafloxacin (STFX) along with fluoroquinolones
      (levofloxacin (LVFX), moxifloxacin (MFLX), garenoxacin (GRNX)) and macrolides
      (azithromycin, clarithromycin) against atypical bacteria (Mycoplasma pneumoniae,
      Legionella pneumophila, Chlamydia trachomatis, Chlamydophila pneumoniae)
      recovered from clinical specimens from 2009 to 2014 at different healthcare
      facilities in Japan were investigated. The minimum inhibitory concentration of
      STFX at which 90% of isolates (MIC90) against M pneumoniae (n= 14) was 0.03MUg/mL
      which was comparable to GRNX, 4- and 16-fold more active than MFLX and LVFX,
      respectively. Reduced susceptibilities of M pneumoniae (9/14 isolates) to
      macrolides were observed. MIC90 of STFX against L. pneumophila (n =15) was
      0.004MUg/mL which was 2- and 4-fold more active than GRNX/LVFX and MFLX,
      respectively. The minimum inhibitory concentration range of STFX against C.
      trachomatis (n=5) and C. pneumoniae (n=5) were from 0.015 to 0.03 and from 0.03
      to 0.06MUg/mL, respectively. Furthermore, differences between the activities of
      STFX against various clinical isolates in 2009 and those in 2012, which were
      already published in two articles (Jpn. J. Antibiotics 63:411- 430, 2010, 66:311
      330, 2013), were also evaluated. The MIC90s of STFX against methicillin-
      susceptible Staphylococcus aureus (MSSA), Streptococcus spp. and Enterococcus
      faecalis isolated in 2012 were 4 or 8 times higher than those in 2009, however
      there was no difference between STFX activities against other species in 2009 and
      those in 2012. In conclusion, STFX showed potent activity against atypical
      bacteria (M pneumoniae, L. pneumophila, C. trachomatis, C. pneumoniae) and no
      tendency for emergence resistance to Gram- positive cocci, Gram-negative bacteria
      and anaerobes except MSSA, Streptococcus spp. andt. faecalis.

PMID- 30226950
TI  - Visual disturbance or central symptom like hallucination in patients treated
      voriconazole: report of six cases.
AB  - Visual disturbance or central symptom like hallucination is well known to be one
      of the common drug adverse events in response to voriconazole (VRCZ). We observed
      123 patients treated VRCZ from April 2012 to January 2016. Two of these cases
      experienced visual disturbance and 4 of these cases experienced central symptom.
      Six patients appeared visual disturbance or central symptom within 1 week after
      administration of VRCZ (visual disturbance; 3 days [2-42 days], central symptom;
      6 days [3-9 days]) and disappeared visual disturbance or central symptom at an
      early date after discontinuation of administration or decreasing dose of VRCZ.
      The trough concentration of VRCZ in patients who experienced central symptom was
      similar with that in-patients who did not experience adverse events by VRCZ (case
      3; 3.79MUg/ mL, case 4; 1.28MUg/mL vs 3.73MUg/mL [0.09-13.27 MUg/mL]). On the
      other hand, the trough concentration of VRCZ in patients who experienced visual
      disturbance was higher than that in patients who did not experience adverse
      events by VRCZ (case 5; 7.49MUg/mL, case 6; 4.45MUg/ mL vs 3.73MUg/mL [0.09
      13.27MUg/mL]). In conclusion, we thought that the risk factor of visual
      disturbance was the increasing concentration of VRCZ. Therefore, we should
      monitor the onset of visual disturbance or central symptom in patients treated
      with VRCZ, especially central symptom that the concentration is unconcerned.

PMID- 30226951
TI  - Historical and hygienic aspects on roles of quality requirements for antibiotic
      products in Japan: Part 4 - Enactment of requirements for individual antibiotic
      products.
AB  - Supplies of high quality antibiotic products to clinics contributed greatly to
      the health maintenance of the citizens of Japan. In this report, we describe the
      results of our investigation and analyses on the establishment and amendments of
      'he quality standards for individual antibiotic products, which were regarded as
      the guidelines for quality control in the production processes. "The minimum
      requirements of penicillin" enacted in May of 1947 was at a relatively moderate
      standard level, due to considerations for domestic technical levels. However,
      after several amendments, in response to the rapid development of manufacturing
      technologies and new penicillin preparations, standards became increasingly
      stricter. "The minimum requirements of streptomycin" enacted in December of 1949
      was prepared by the use of streptomycin preparations imported from the USA. The
      3rd and 4th standards, "the minimum requirements of dihydrostreptomycin" and "the
      minimum requirements of chloramphenicol", were prepared by applying provisions
      described in the rules for certification of the U.S. Food and Drug
      Administration. In accordance with an increase in the varieties of antibiotic
      products, "the minimum requirements of antibacterial products" was enacted by the
      integration of previously existing standards and newly enacted ones. Thereafter,
      in response to the innovation of scientific technologies and the globalization of
      antibiotic products, "the minimum requirements for antibiotic products in Japan"
      was further developed and became the basis for supplying high quality antibiotic
      preparations.

PMID- 30226952
TI  - Historical and hygienic aspects on roles of quality requirements for antibiotic
      products in Japan: Part 5 - Introduction of technology and knowledge on
      streptomycin production from the United States of Americat.
AB  - In order to investigate the roles of quality requirements for antibiotics
      products in Japan, from historical and hygienic aspects, we examined how
      technology and knowledge in the production and quality control of streptomycin
      were introduced from the United States of America. In this study, through
      detailed investigations and analyses, it was confirmed that the introduction of
      technology and knowledge on streptomycin was strongly supported by Brigadier
      General CRAWFORD SAms, the chief of the Public Health and Welfare Section (PHW)
      of the Supreme Commander for Allied Powers/General Headquarters, via the Ministry
      of Welfare in Japan. Dr. SELMAN WAKSMAN, the discoverer of streptomycin, along
      with scientists of Merck & Co., also helped Japanese industries extensively, via
      PHW, by providing the original streptomycin-producing strains and transferring
      expertise in streptomycin production. With the technology and knowledge being
      introduced from the USA, domestic production of streptomycin preparations
      increased very rapidly. As noted in our previous report, domestic production
      reached amounts enough to satisfy national demand within three years. Japanese
      people have a racial tendency to be highly susceptible to tuberculosis known as
      an incurable national disease. Thanks to streptomycin therapy, the tuberculosis
      mortality rate (per 100,000 population) had fallen dramatically within only five
      years from 187.2 in 1947 to 82.2 in 1952.

PMID- 30226953
TI  - Clinical analysis of the pediatric inpatients with lower respiratory tract
      infection due to human metapneumovirus.
AB  - Human metapneumovirus (hMPV) is known as one of popular agents of acute
      respiratory infection in children. We reviewed the patients' background, result
      of initial blood test, bacterial culture, chest X-ray and clinical features of
      hospitalized children with lower respiratory tract infections caused by hMPV from
      March 2014 to February 2015 and compared them with the infections due to
      respiratory syncytial virus (RSV) and other causative agents. Of 419 patients
      tested by rapid virus antigen tests, 35 were positive for hMPV, 145 were positive
      for RSV, and 239 were negative for both viruses. Most of hMPV infections occurred
      between March and June, and 72% of households of hMPV-positive children got sick.
      hMPV-positive children did not have any specific symptoms such as wheezing in RSV
      positive children. However, many of them were admitted due to prolonged high
      fever and/or ill appearance despite of no respiratory distress. Although it is
      said that hMPV-positive children admitted to hospitals tend to have pneumonia,
      the ratio of children'with pneumonia in this study was less than 60%.

PMID- 30226954
TI  - Investigations on yearly changes in tebipenem susceptibility of bacterial
      isolates from pediatric patients -A post-marketing surveillance of tebipenem
      pivoxil granules for pediatric.
AB  - We conducted the post-marketing surveillance of tebipenem pivoxil (Orapeneme fine
      granules 10% for pediatric), an oral carbapenem antibacterial agent, to
      investigate changes in bacterial susceptibility against tebipenem (TBPM).
      Bacterial strains used in this surveillance were methicillin-susceptible
      Staphylococcus aureus (MSSA: 303 strains), Streptococcus pneumoniae (554
      strains), other Streptococcus spp. (242 strains: including Streptococcus pyogenes
      133 strains), Moraxella catarrhalis (306 strains) and Haemophilus influenzae (506
      strains) isolated from pediatric patients in 15 medical facilities in Japan
      between April 2010 and March 2015. Investigation was conducted three times (April
      2010-March 2011, April 2012-March 2013 and April 2014-March 2015), and in any of
      these investigation periods, there were a large number of isolates from infants
      in terms of the frequency of isolates by age. The MIC90s of TBPM against MSSA, S.
      pneumoniae, other Streptococcus spp., M. catarrhalis and H. influenzae in these
      investigations were 0.015-0.03, 0.06, 0.008-0.015 (0.002 for S. pyogenes), 0.03
      and 0.5-1 MUg/mL, respectively, which were less than 2-fold, and a remarkable
      increase in MIC90 was not shown. On the other hand, the MIC50s of carbapenems
      including TBPM and penicillins against S. pneumoniae decreased to 1/4-1/8 during
      the investigation periods, and decreased gPRSP*1 (48.7% - 26.1%) and increased
      gPISP (2x)*2 (24.1% -+ 46.8%) were suggested to be involved in these changes in
      susceptibility. In S. pneumoniae, a decrease of macrolides-resistant strains due
      to mefA*3 (38.5% - 18.8%) and an increase of macrolides-resistant strains due to
      ermB*4 (41.7% - 62.4%) were noted. In H. influenzae, the frequencies of gBLNAR*5
      and beta-lactamase-producing strains were about 60-70% and 7-9%, respectively,
      and a remarkable change in susceptibility was not shown. As a result of
      investigations in the susceptibility of clinical isolates collected from
      pediatric patients as post-marketing surveillance, there was no decrease in TBPM
      susceptibility noted.

PMID- 30226955
TI  - Evaluation of rapid measurement of Chlamydia trachomatis and Neisseria
      gonorrhoeae by using automatic gene analyzer "GENECUBE".
AB  - Nucleic acid amplification tests (NAATs) are considered as one of critical
      diagnostic methods on Chlamydia trachomatis and Neisseria gonorrhoeae infections
      due to their high sensitivity and accuracy. However, conventional NAATs required
      2-6 hours to complete the measurements including extraction, amplification, and
      detection of the target nucleic acids. To reduce the time, we evaluated the
      clinical significance of the rapid NAAT using GENECUBE (TOYOBO CO., LTD.) which
      can complete the measurement within 1 hour. We compared the performance of
      GENECUBE with those of TMA method (APTIMA" Combo2 chlamydia/ gonorrhoeae, Hologic
      Japan, Inc.) and lateral flow immunochromatographic assay (Clearview Chlamydia,
      Clearview gonorrhoeae, Alere Medical Co., Ltd.) by detecting specimens from 96
      cervical swabs. The overall agreement results between GENECUBE and TMA were 95.8%
      and 100% for C. trachomatis and N. gonorrhoeae, respectively. The results
      suggested that GENECUBE showed equivalent sensitivity and specificity of TMA.
      Indeed, more than half of the positive samples in NAATs were measured as negative
      in the lateral flow. The lateral flow is known as a rapid assay, however the
      results revealed its poor sensitivity. We think rapid NAATs using GENECUBE on C.
      trachomatis and N. gonorrhoeae can be one of the methods, which realize rapid
      tests with high sensitivity and accuracy.

PMID- 30226956
TI  - The 65th Japan Hospital Association (JHA) Congress 2015 Karuizawa Desirable
      Healthcare System Reform: How Hospitals Should Handle System Reform.

PMID- 30226957
TI  - Making Guarantees in Healthcare - Why Not?.

PMID- 30226958
TI  - In Healthcare - When Is Good Enough, Good Enough?.

PMID- 30226959
TI  - Estimating the Impact of the New Income Deduction System for Over-the-Counter
      Drug Expenses.

PMID- 30226960
TI  - Development of Case Mix Based Evaluation System in Japan.
AB  - DPC (Diagnosis Procedure Combination) is the Japanese original Case Mix system.
      The principal purpose of DPC introduction is not only for payment arrangement but
      also for modernization of the health system. To improve the quality of hospital
      management, to strengthen the responsibility of hospital for accountability, and
      to rationalize the health system are the three main objectives of the project.
      Based on the current DPC database, patients can know the clinical performance of
      each acute care hospital, such as volume stratified by diseases and disorders and
      related quality indicators. Furthermore, DPC data is used for regional health
      care planning. In this article, the author provides an overview of the DPC system
      with some examples.

PMID- 30226961
TI  - Hospitals and Big Data: Use of Case Mix and E-claim Data in Japan.
AB  - The ageing society issue has necessitated the Japanese government conducting
      health reform. In order to reorganize the health service delivery system, the
      Ministry of Health, Labour and Welfare (MHLW) has prepared two massive health
      related data bases; DPC (Diagnosis Procedure Combination) data and NDB (National
      Receipt Database). The former gathers about 11 million discharged cases from
      1,900 acute care hospitals annually. The latter gathers more than 1.7 billion
      claim data from all medical facilities every year. Using these data bases, we can
      evaluate the current system and estimate the future health needs of each region.
      As the backbone of the Japanese health system is a publicly funded private
      dominant supply system, the existence of useful information concerning health
      needs is crucial for sound management, especially for the private sector. In this
      article, the author reveals some examples of the application of these two massive
      databases for regional health planning and hospital management.

PMID- 30226962
TI  - Financial Burden and Employment Support for Patients with Cancer in Japan: A
      Review.
AB  - AIM AND METHOD: To improve employment support measures for patients with cancer,
      the author collected study reports and material published from January 2010
      through January 2016 and analyzed cancer epidemiology, treatment costs, cancer's
      negative impact on patients, resignation rates, factors affecting employment, and
      the state of support in Japan. RESULTS: Approximately 30% of workers suffering
      from cancer (regular employees: 21%; non-regular employees: 39%) resigned from
      work. Over 80% of patients with cancer wished to remain employed (nearly 70%
      among patients who had resigned following incidence of cancer) in order to
      maintain their households and quality of life and cover cancer treatment costs.
      Approximately half of the Japanese companies surveyed did not grasp the
      employees' cancer incidence, considering it to be a private injury. Additionally,
      74% of companies had not recorded one month or more of absences due to cancer-
      related sickness. Nonetheless, among large companies, around 70% of regular
      employees with cancer were able to return to work (RTW) within one year of the
      start of cancer-related sickness absence (81% returned working shorter hours; 62%
      returned to full-time work). CONCLUSIONS: A year of sickness absence and shorter
      working hours enables employees with cancer to RTW. Employment continuation
      support should principally promote RTW from the initial announcement of cancer.
      The author proposes a modified health promotion management strategy that aims to
      ensure a safe RTW through employers' systematic initiatives and with employees'
      collaborative effort to improve wellness in the corporate community.
      Collaboration between hospitals, companies' industrial medical staff, and company
      staff will facilitate RTW. Policy aimed at reducing hospital stays requires that
      ambulatory nurses in hospitals plan long-term individual nursing care and provide
      high-quality nursing care tailored to the various needs of patients, according to
      the Information Prescription. However, this service's medical fee valuation is
      low. Improving ambulatory nursing therefore requires increasing this fee.

PMID- 30226963
TI  - EVALUATION OF MULTIPLEX LIGATION DEPENDENT PROBE AMPLIFICATION AS A TOOL FOR
      DIAGNOSIS AND CARRIER DETECTION IN FAMILIES WITH A DYSTROPHINOPATHY.
AB  - We set out to evaluate multiplex ligation dependent probe amplification (MLPA) as
      a tool for diagnosis and carrier detection in families with a dystrophinopathy.
      Fifty three Indian families with provisional diagnosis of Duchene muscular
      dystrophy or Becker muscular dystrophy were evaluated by MLPA and multiplex
      polymerase chain reaction (PCR). Sanger sequencing was used to analyze the entire
      gene in one patient. Mothers were tested for carrier status whenever possible.
      Molecular analysis of DMD gene by combining MLPA and multiplex PCR yielded a
      mutation detection rate of 62% (33/53). Deletions were detected in 27/53 (51%)
      cases, duplications in 5/53 (9%) cases, a small deletion one case and Sanger
      sequencing detected a nonsense mutation in one case. Mutation was not detected in
      36% (19/53) cases. Fifty six percent of mothers (9/16) were found to be carriers.
      MLPA helped to refine the results of multiplex PCR testing in 22 patients (5
      duplications, 16 deletions and one small deletion). We also describe a situation
      where a deletion of single exon on MLPA (but not detected by multiplex PCR) was
      actually due to a deletion of two nucleotides in the probe ligation site. MLPA
      appears to score over multiplex PCR in diagnosis and carrier detection,
      specifically by detecting deletions and duplications that are not detected by
      traditional multiplex PCR.

PMID- 30226964
TI  - EVALUATION OF PREIMPLANTATION GENETIC ANEUPLOIDY SCREENING CASES AT A REFERENCE
      GENETICS CENTER: 10 YEARS' EXPERIENCE.
AB  - The aim of this study is to review and evaluate our preimplantation genetic
      screening (PGS) records in terms of their demographic data, indications,
      cytogenetic results, pregnancy outcomes and discuss these findings in different
      aspects. PGS was performed in a total of 84 couples (87 cycles) between the
      period 2005 to 2015. Biopsied blastomeres from embryos on day 3 were fixed and
      fluorescence in situ hybridization was carried out for chromosomes 13, 16, 18,
      21, 22, X and Y depending on the indication. The diagnostic and clinical data
      were retrospectively evaluated. A total of 450 blastomeres were biopsied. Ninety
      eight of them were found to be suitable for transfer. They were transferred to 72
      patients in 75 cycles resulting in 23 pregnancies and 20 healthy births. The most
      common indication was unexplained infertility. The implantation rate was
      calculated as 23.4% whereas the take-home baby rate was 26.6% per transfer. The
      highest rate of healthy living births is achieved in patients having low grade
      maternal mosaic sex chromosomal aneuploidy. All living births achieved by PGS had
      normal chromosomal structure which we can propose it as an alternative test for
      couples at risk to select normal embryos to improve the outcomes of assisted
      reproductive procedures and to avoid the transfer of chromosomally unbalanced and
      multiple embryos.

PMID- 30226965
TI  - MECP2 DUPLICATION SYNDROME WITH ADDITIONAL FINDINGS.
AB  - Rett syndrome (RTT) and Angelman syndrome (AS) are devastating neurological
      disorders that participate in overlapping clinical features with autism spectrum
      disorders (ASDs). It has been reported that in addition to common mutations or
      deletions, individuals with chromosomal duplications including either the MECP2
      or UBE3A loci show clinical features related to those of MECP2 duplication
      syndrome, AS, or ASDs. Here we report a 10-year--10-months old male patient
      having overlapping clinical features of MECP2 duplication syndrome, AS and ASDs.
      He had mental retardation, lack of speech and developmental delay, and also
      dysmorphic features such as plagiocephaly, retrognathia, hyperextensible joints
      in fingers and elbows, broad great toe and three different sizes of cafe au
      laits. The X-ray revealed compound craniosynostosis and the cranial MRI at 10
      years showed delayed myclination. Due to his clinical features, we performed
      molecular karyotyping and found numerous genomic alterations. Two of these
      genomic alterations including duplications of chromosome Xq28 and 15qll.2ql3.l1
      were found to be compatible with his clinical findings. According to methylation
      analysis, duplicated UBE3A gene found to be not methylated. The present case
      study may contribute to a better definition and an improved comprehension of the
      overlapping pathways of MECP2 and UBE3A.

PMID- 30226966
TI  - EXPANSION OF THE SHORT SYNDROME PHENOTYPE IN AN ADULT PATIENT WITH UNILATERAL
      BASAL GANGLIA CALCIFICATION.
AB  - SHORT syndrome is a rare autosomal dominant disorder whose acronym stands for
      short stature, hyperextensibility of joints and/or hernias, ocular depression,
      Rieger anomaly, and teething delay. Common clinical features include intrauterine
      and postnatal growth restriction, lipoatrophy, characteristic facial gestalt,
      anterior chamber defects and insulin resistance/diabetes. To date, the
      coexistence of SHORT syndrome and unilateral basal ganglia calcification has not
      been reported. Here, we describe a 27-year-old woman bom to healthy first-cousin
      Mexican parents who exhibited the SHORT syndrome phenotype and unilateral basal
      ganglia calcification. The current observation provides additional knowledge of
      the spectrum of anomalies that can occur in SHORT syndrome and further
      illustrates the clinical variability of this disorder. Therefore, basal ganglia
      calcification and other brain abnormalities should be specifically looked for in
      all affected patients in order to provide appropriate medical management and
      genetic counseling.

PMID- 30226967
TI  - A CASE OF CONFINED PLACENTAL MOSAICISM WITH TRISOMY 15 ASSOCIATED WITH TURNER
      SYNDROME.
AB  - We here present a rare case of a Turner syndrome with mosaic trisomy 15
      identified on chorionic villous sampling (CVS). Although there are several
      reports in the literature indicating confined placental mosaicism (CPM),
      counseling parents of a fetus with trisomy 15 mosaicism at CVS remains difficult
      because of the phenotypic variability. To illuminate that condition an
      amniocentesis or cord blood study should be offered in conjunction with genetic
      counseling.

PMID- 30226968
TI  - CLINICAL EFFECT OF A MUTATION (p.Glu322Asp, c.966 G>T) IN PANK2 GENE IN A FAMILY
      WITH ATYPICAL PANTOTHENATE KINASE-ASSOCIATED NEURODEGENERATION.
AB  - Pantothenate-kinase-associated neurodegeneration (PKAN) is a rare autosomal
      recessive disorder caused by mutations in the pantothenate kinase 2 (PANK2) gene.
      Many different mutations in the PANK2 gene have been detected in association with
      PKAN. A 20 year old female patient who had been suffering from progressive gait
      disorder for 1 year was found to have the 'eye-of-the-tiger sign' from the brain
      magnetic resonance imaging (MRI). The same brain imaging findings were shown in
      the father and brother of the patient, whose parents arranged a consanguineous
      marriage. We found c.966 G>T (p.Glu322Asp) mutation in the PANK2 gene mutation
      analysis in the individuals from the brain imaging findings. Although individuals
      in this family who had a homozygous mutation in PANK2 gene analyses had the 'eye
      of-the-tiger' sign and atypical disease, they were noted to have differing
      clinical findings.

PMID- 30226969
TI  - BARTH SYNDROME IN MALE AND FEMALE SIBLINGS CAUSED BY A NOVEL MUTATION IN THE TAZ
      GENE.
AB  - Barth syndrome (BTHS) is an X-linked recessive disease caused by mutations in
      tafazzin gene (TAZ) which lead to cardiolipin deficiency and mitochondrial
      dysfunction. Male patients have variable clinical findings, including
      cardiomyopathy, skeletal myopathy, prepubertal short stature, neutropenia and 3
      methylglutaconic aciduria. Female carriers are usually asymptomatic. We report a
      novel TAZ gene mutation in male and female siblings with left ventricular
      noncompaction and hypotonia. Additionally, the brother presented an intermittent
      neutropenia and increased urinary levels of 3-methylglutaconic and 3
      methylglutaric acid. The molecular genetic testing showed that both siblings
      carry the mutation: c.253insC, p.(Arg85Profs*54) in exon 3 of the TAZ gene. This
      article presents the first case of BTHS in a heterozygous female patient with
      normal karyotype.

PMID- 30226970
TI  - MICRODUPLICATION OF 17p[DUP(17)(12p11.2)]: REPORT OF A NEONATE WITH A SPINA
      BIFIDA AND CARDIAC ANOMALIES AND A LITERATURE REVIEW.
AB  - Duplication 17pll.2 syndrome is a recent recognized syndrome with multiple
      congenital anomalies and mental retardation. Most patients with duplication
      17p11.2 syndrome harbor a common 3.7 Mb duplication (17p.11.2 duplication
      syndrome) resulting in congenital anomalies, neurodevelopmental and behavioral
      phenotypes. We report a case with spina bifida, tetralogy of Fallot and a small
      duplication (932 Kb) of 17pl1.2 containing approximately 20 genes, detected by
      array-CGH. We describe clinical features not reported previously for
      microduplication of 17p11.2.

PMID- 30226971
TI  - A NEONATE PRESENTING WITH GRACILE SYNDROME AND BJORNSTAD PHENOTYPE ASSOCIATED
      WITH BCS1L MUTATION.
AB  - GRACILE Syndrome, is an autosomal recessive disease presenting with growth
      retardation, severe lactic acidosis, Fanconi type tubulopathy, cholestasis, iron
      overload and early death without any dysmorphological or neurological features.
      The BCSIL gene mutation is responsible for GRACILE syndrome, Bjornstad syndrome
      and complex III deficiency. Bjomstad syndrome is characterized by sensorineural
      hearing loss and abnormal flat twisted hair shafts. The case is GRACILE syndrome
      with Bjomstad phenotype in neonatal period due to BCSL1 gene mutation.

PMID- 30226972
TI  - A THANATOPHORIC DYSPLASIA TYPE I CASE WITH A FGFR3 P.R248C MUTATION AND SURVIVAL
      BEYOND THE NEONATAL PERIOD.
AB  - A Thanatophoric dysplasia, is a severe congenital anomaly which mostly causes
      stillbirth or death of the affected baby within hours due to respiratory
      insufficiency. The diagnosis of TD is typically suspected on ultrasound during
      the second trimester of pregnancy, when severe shortening of the long bones,
      frontal bossing, flattened vertebrae, and short ribs that result in a narrow
      thorax and bell-shaped abdomen, can be seen. Here, we present a case with
      prenatal ultrasonographic findings suggestive of TD, and highlight the patient's
      postnatal dysmorphic features and typical radiographic findings. The definitive
      diagnosis of TD type I (TDI) was made postnatally, when molecular genetic
      analysis revealed the previously described p.R248C mutation in FGFR3. This case
      is reported due to its relative long life span and the definitive molecular
      diagnosis that could be made during hospitalization.

PMID- 30226973
TI  - TWO DIFFERENT MUTATIONS OF GL13 GENE IN TWO DIFFERENT SYNDROMES.
AB  - Polydactyly is among comnion extremity abnormalities. Mutations of GLI3 gene have
      been reported commonly in Greig Cephalopolysyndactyly Syndrome (GCPS) and
      Pallister-Hall Syndrome (PHS). We have determined two different mutations of GLI3
      gene in two different cases, one of which is with GCPS and the other one is with
      PHS. A deletion mutation was detected in the proband with GCPS and his mother.
      Otherwise, we found that, unlike the previously reported, the mutation c.2437C>T,
      p.Q813X which was detected in the GLI3 gene caused typical PHS. We are in thought
      of that our cases will contribute to understanding of phenotypic variability
      leading to GLI3 mutations.

PMID- 30226974
TI  - A NOVEL MUTATION K447M (P.LYS447MET, C.1340 A>T) IDENTIFIED IN EXON 4 OF THE MEFV
      GENE.

PMID- 30226975
TI  - DID A del(2)(p11.2p13),inv(2)(p11.2q31) REARRANGEMENT RESULT FROM A GERMLINE
      RECIPROCAL INTRACHROMOSOME INSERTION?

PMID- 30226976
TI  - PRENATAL DIAGNOSIS OF RHIZOMELIC CHONDRODYSPLASIA PUNCTATA.

PMID- 30226977
TI  - Visible Light Activation of Nucleophilic Thiol-X Addition via Thioether Bimane
      Photocleavage for Polymer Cross-Linking.
AB  - On-demand photo-uncaging of reactive thiols have been employed in engineering
      biomaterial scaffolds for regulation of cellular activities. A drawback of the
      current photo-uncaging chemistry is the utilization of high energy UV light or 2
      photon laser light, which may be harmful to cells and cause undesired side
      reactions within the biological environment. We introduce an effective approach
      for the caging of thiol using monobromobimane, which can be removed under
      irradiation of light at lambda = 420 nm and in the presence of electrophiles,
      such as acrylate, propiolate and maleimide, for trapping of the newly release
      thiol. This chemical approach can be used in visible light-induced polymer
      coupling and cross-linking for the preparation of cell-laden hydrogels.

PMID- 30226978
TI  - Intelligent Biomimetic Chameleon Skin with Excellent Self-Healing and
      Electrochromic Properties.
AB  - Animals such as chameleons possess a natural ability to adjust their skin color
      as a preventive measure to deter any potential threat and to self-heal damaged
      skin tissues. Inspired by this, we present here a copolymer film possessing
      biomimetic properties that simultaneously integrates electrochromic
      triphenylamine and self-healing Diels-Alder groups. The flexible and stretchable
      copolymer film acts like natural chameleon skin, which exhibits significant color
      variation and also possesses excellent self-healing properties. These remarkable
      features make it a promising material for overcoming the crack-generation issue
      inherited by conventional biomimetic chameleon skin. Moreover, a flexible and
      wearable skin device based on the copolymer film with silver fabric as a
      electrode has also been fabricated. The electrochromic and self-healing
      properties were verified for the copolymer film, and it has been elucidated that
      the intelligent biomimetic "chameleon skin" was a new step toward the development
      of highly advanced biomimetic materials and devices.

PMID- 30226979
TI  - Light-Emitting Covalent Organic Frameworks: Fluorescence Improving via Pinpoint
      Surgery and Selective Switch-On Sensing of Anions.
AB  - Covalent organic frameworks (COFs) offer ordered pi structures that are useful
      for developing light-emitting materials. However, most COFs are weak in
      luminescence. Here we report the conversion of less emissive COFs into light
      emitting materials via a pinpoint surgery on the pore walls. Deprotonation of the
      N-H bond to form an anionic nitrogen species in the hydrazone linkage can
      eliminate the nitrogen-related fluorescence quenching pathway. The resulting COF
      enhances the fluorescence in a linear proportion to the progress of
      deprotonation, achieving a 3.8-fold improved emission. This pinpoint N-H cleavage
      on the pore walls can be driven only by the fluoride anion while other halogen
      anions, including chloride, bromide, and iodide, remain inactive, enabling the
      selective fluorescence switch-on sensing of the fluoride anion at a ppb level.

PMID- 30226981
TI  - Engineering Bacillus megaterium Strains To Secrete Cellulases for Synergistic
      Cellulose Degradation in a Microbial Community.
AB  - Recent environmental concerns have intensified the need to develop systems to
      degrade waste biomass for use as an inexpensive carbon source for microbial
      chemical production. Current approaches to biomass utilization rely on
      pretreatment processes that include expensive enzymatic purification steps for
      the requisite cellulases. We aimed to engineer a synthetic microbial community to
      synergistically degrade cellulose by compartmentalizing the system with multiple
      specialized Bacillus megaterium strains. EGI1, an endoglucanase, and Cel9AT, a
      multimodular cellulase, were targeted for secretion from B. megaterium. A small
      library of signal peptides (SPs) with five amino acid linkers was selected to tag
      each cellulase for secretion from B. megaterium. Cellulase activity against
      amorphous cellulose was confirmed through a series of bioassays, and the most
      active SP constructs were identified as EGI1 with the LipA SP and Cel9AT with the
      YngK SP. The activity of the optimized cellulase secretion strains was
      characterized individually and in tandem to assess synergistic cellulolytic
      activity. The combination of EGI1 and Cel9AT yielded higher activity than either
      single cellulase. A coculture of EGI1 and Cel9AT secreting B. megaterium strains
      demonstrated synergistic behavior with higher activity than either monoculture.
      This cellulose degradation module can be further integrated with bioproduct
      synthesis modules to build complex systems for the production of high value
      molecules.

PMID- 30226980
TI  - Nanoradiator-Mediated Deterministic Opto-Thermoelectric Manipulation.
AB  - Optical manipulation of colloidal nanoparticles and molecules is significant in
      numerous fields. Opto-thermoelectric nanotweezers exploiting multiple coupling
      among light, heat, and electric fields enables the low-power optical trapping of
      nanoparticles on a plasmonic substrate. However, the management of light-to-heat
      conversion for the versatile and precise manipulation of nanoparticles is still
      elusive. Herein, we explore the opto-thermoelectric trapping at plasmonic
      antennas that serve as optothermal nanoradiators to achieve the low-power (~0.08
      mW/MUm2) and deterministic manipulation of nanoparticles. Specifically, precise
      optical manipulation of nanoparticles is achieved via optical control of the
      subwavelength thermal hot spots. We employ a femtosecond laser beam to further
      improve the heat localization and the precise trapping of single ~30 nm
      semiconductor quantum dots at the antennas where the plasmon-exciton coupling can
      be tuned. With its low-power, precise, and versatile particle control, the opto
      thermoelectric manipulation can have applications in photonics, life sciences,
      and colloidal sciences.

PMID- 30226982
TI  - Interspecies Variation between Fish and Human Transthyretins in Their Binding of
      Thyroid-Disrupting Chemicals.
AB  - Thyroid-disrupting chemicals (TDCs) are xenobiotics that can interfere with the
      endocrine system and cause adverse effects in organisms and their offspring. TDCs
      affect both the thyroid gland and regulatory enzymes associated with thyroid
      hormone homeostasis. Transthyretin (TTR) is found in the serum and cerebrospinal
      fluid of vertebrates, where it transports thyroid hormones. Here, we explored the
      interspecies variation in TDC binding to human and fish TTR (exemplified by
      Gilthead seabream ( Sparus aurata)). The in vitro binding experiments showed that
      TDCs bind with equal or weaker affinity to seabream TTR than to the human TTR, in
      particular, the polar TDCs (>500-fold lower affinity). Crystal structures of the
      seabream TTR-TDC complexes revealed that all TDCs bound at the thyroid binding
      sites. However, amino acid substitution of Ser117 in human TTR to Thr117 in
      seabream prevented polar TDCs from binding deep in the hormone binding cavity,
      which explains their low affinity to seabream TTR. Molecular dynamics and in
      silico alanine scanning simulation also suggested that the protein backbone of
      seabream TTR is more rigid than the human one and that Thr117 provides fewer
      electrostatic contributions than Ser117 to ligand binding. This provides an
      explanation for the weaker affinities of the ligands that rely on electrostatic
      interactions with Thr117. The lower affinities of TDCs to fish TTR, in particular
      the polar ones, could potentially lead to milder thyroid-related effects in fish.

PMID- 30226983
TI  - Impact of Film Thickness on Defects and the Graphitization of Nanothin Carbon
      Coatings Used for Metallic Bipolar Plates in Proton Exchange Membrane Fuel Cells.
AB  - Metallic bipolar plates (BPPs) are considered promising alternatives to
      traditional graphite BPPs used in proton exchange membrane fuel cells (PEMFCs).
      Major auto companies, such as Toyota, GM, Ford, and BMW, are focusing on the
      development of metallic BPPs. Amorphous carbon (a-C) coating are widely known to
      be effective at enhancing the performance of metallic BPPs. However, a-C coatings
      prepared by sputtering are mostly micrometers thick, which can render mass
      production difficult due to their low deposition rates. In this study, we
      investigate effects of thickness on the formation of defects and the
      graphitization of nanothin a-C layers deposited by magnetron sputtering from
      scanning electron microscope (SEM) and transmission electron microscope (TEM)
      observations, internal stress measurements, X-ray diffractometer (XRD) data,
      Raman spectra, and X-ray photoelectron spectroscopy (XPS). Furthermore, corrosion
      and interfacial contact resistance (ICR) test results show that an approximately
      69 nm a-C layer, with a deposition time of only 15 min, can meet ex situ
      technical targets of US Department of Energy. As the thickness of a-C layers
      increases, vacancy-like defects become more pronounced, which is accompanied by
      stress relaxation. Furthermore, the larger the graphite-like clusters, the more
      sp2-hybridization carbon atoms found in loose a-C films. The good properties of
      nanothin a-C layers are attributed to their limited defects and proper
      graphitization.

PMID- 30226984
TI  - Biomarkers of Whole Grain Intake.
AB  - There is growing evidence that whole grain (WG) intake may prevent many chronic
      diseases. However, there are mixed results on this topic in human studies as a
      result of a lack of accurate tools to assess the intake of WGs and individual
      metabolic variation. To better understand the effects of WGs on health
      maintenance and the risk of chronic disease, there is an urgent need to identify
      the biomarkers for WG intake. The molecular signatures of WG intake remain
      undefined. This perspective gives an overview of the current knowledge,
      challenges, and future directions on the biomarkers of WG intake.

PMID- 30226985
TI  - Introduction of Protonated Sites on Exfoliated, Large-Area Sheets of Hexagonal
      Boron Nitride.
AB  - Hexagonal boron nitride (h-BN) sheets possess an exclusive set of properties,
      including wide energy band gap, high optical transparency, high dielectric
      breakdown strength, high thermal conductivity, UV cathodoluminescence, and
      pronounced thermochemical stability. However, functionalization of large h-BN
      layers has remained a challenge due to their chemical resistance and unavailable
      molecular-binding sites. Here we report on the protonation of h-BN via treatment
      with chlorosulfonic acid that not only exfoliates "large" h-BNs (up to 10 000
      MUm2) at high yields (~23%) but also results in their covalent functionalization
      by introducing four forms of aminated nitrogen (N) sites within the h-BN lattice:
      sp2-delocalized and sp3-quaternary protonation on internal N sites (>N+? and >NH+
      ) and pyridinic-like protonation on the edge N sites (?NH+- and -NH-). The
      presence of these groups transforms the chemically passive h-BN sheets to their
      chemically active form, which as demonstrated here can be used as scaffolds for
      forming composites with plasmonic gold nanoparticles and organic dye molecules.
      The dispersion of h-BNs exhibits an optical energy band gap of 5.74 eV and a zeta
      potential of zeta = +36.25 mV at pH = 6.1 (zetamax = +150 mV), confirming high
      dispersion stability. We envision that these two-dimensional nanomaterials with
      an atomically packed honeycomb lattice and high-energy band gap will evolve next
      generation applications in controlled-UV emission, atomic-tunneling-barrier
      devices, ultrathin controlled-permeability membranes, and thermochemically
      resistive transparent coatings.

PMID- 30226987
TI  - In Silico Identification of JMJD3 Demethylase Inhibitors.
AB  - In the search for new demethylase inhibitors, we have developed a multistep
      protocol for in silico screening. Millions of poses generated by high-throughput
      docking or a 3D-pharmacophore search are first minimized by a classical force
      field and then filtered by semiempirical quantum mechanical calculations of the
      interaction energy with a selected set of functional groups in the binding site.
      The final ranking includes solvation effects which are evaluated in the continuum
      dielectric approximation (finite-difference Poisson equation). Application of the
      multistep protocol to JMJD3 jumonji demethylase has resulted in a dozen low
      micromolar inhibitors belonging to five different chemical classes. We have
      solved the crystal structure of JMJD3 inhibitor 8 in the complex with UTX (a
      demethylase in the same subfamily as JMJD3) which validates the predicted binding
      mode. Compound 8 is a promising candidate for future optimization as it has a
      favorable ligand efficiency of 0.32 kcal/mol per nonhydrogen atom.

PMID- 30226986
TI  - Nitrogen Feeding Strategies and Metabolomic Analysis To Alleviate High-Nitrogen
      Inhibition on Docosahexaenoic Acid Production in Crypthecodinium cohnii.
AB  - It is well-known that high-nitrogen content inhibits cell growth and
      docosahexaenoic acid (DHA) biosynthesis in heterotrophic microalgae
      Crypthecodinium cohnii. In this study, two nitrogen feeding strategies, pulse
      feeding and continuous-feeding, were evaluated to alleviate high-nitrogen
      inhibition effects on C. cohnii. The results showed that continuous-feeding with
      a medium solution containing 50% ( w/v) yeast extract at 2.1 mL/h during 12-96 h
      was the optimal nitrogen feeding strategy for the fermentation process, when
      glucose concentration was maintained at 15-27 g/L during the same period. With
      the optimized strategy, 71.2 g/L of dry cell weight and DHA productivity of 57.1
      mg/L/h were achieved. In addition, metabolomic analysis was applied to determine
      the metabolic changes during different nitrogen feeding conditions, and the
      changes in amino acids, polysaccharides, purines, and pentose phosphate pathway
      were observed, providing valuable metabolite-level information for exploring the
      mechanism of the high-nitrogen inhibition effect and further improving DHA
      productivity in C. cohnii.

PMID- 30226988
TI  - The Rate of Charge Tunneling in EGaIn Junctions Is Not Sensitive to Halogen
      Substituents at the Self-Assembled Monolayer//Ga2O3 Interface.
AB  - This paper describes experiments that are designed to test the influence of
      terminal groups incorporating carbon-halogen bonds on the current density (by
      hole tunneling) across self-assembled monolayer (SAM)-based junctions of the form
      MTS/S(CH2)9NHCOCH nX3- n//Ga2O3/EGaIn (where M = Ag and Au and X = CH3, F, Cl,
      Br, I). Within the limits of statistical significance, these rates of tunneling
      are insensitive to the nature of the terminal group at the interface between the
      SAM and the Ga2O3. The results are relevant to the origin of an apparent
      inconsistency in the literature concerning the influence of halogen atoms at the
      SAM//electrode interface on the tunneling current density.

PMID- 30226989
TI  - Temperature-Dependent Infrared Photodissociation Spectroscopy of (CO2)3+ Cation.
AB  - Infrared photodissociation spectra of He-buffer-gas-cooled (CO2)3+ were measured
      at ion trap temperatures of 15, 50, 150, and 280 K. Electronic structure
      calculations at the mPW2PLYPD/aug-cc-pVDZ level were performed to identify the
      structures of the low-lying isomers and to assign the observed spectral features.
      The experimental and calculated infrared spectra show that the (CO2)3+ cations
      formed in the source are primarily dominated by the charge partially delocalized
      C2O4+ motif, in which the positive charge is partially delocalized over the two
      CO2 molecules. Thermal heating at elevated internal temperature supplies
      sufficient energy to overcome the isomerization barriers and gives access to the
      charge completely delocalized (CO2) n+ ( n = 3) motif, in which the positive
      charge is almost completely delocalized over all of the constituent CO2
      molecules.

PMID- 30226990
TI  - Changes of S-Allylmercaptocysteine and gamma-Glutamyl- S-allylmercaptocysteine
      Contents and Their Putative Production Mechanisms in Garlic Extract during the
      Aging Process.
AB  - gamma-Glutamyl- S-allylmercaptocysteine (GSAMC), a putative precursor compound of
      S-allylmercaptocysteine (SAMC), was isolated and identified from aged garlic
      extract (AGE). We analyzed the change of their contents in AGE during the aging
      process, chronologically from 1 to 22 months. The formation of these compounds
      occurred mostly during the early stage of the aging period: the SAMC content
      reached a maximum at approximately 4 months, whereas the GSAMC content reached a
      maximum at 1 month and then decreased during the subsequent aging period. To
      assess the possible relationship between the change of the two compounds during
      the aging process, we set up the model reactions with the hypothesis that GSAMC
      is produced from gamma-glutamyl- S-allylcysteine (GSAC)/gamma-gultamyl- S-1
      propenylcysteine (GS1PC) and that SAMC is produced from GSAMC by endogenous gamma
      glutamyl transpeptidase (GGT) in garlic during the early stage of the aging
      process. We found that, in the model reactions, SAMC was produced from GSAMC by
      the garlic protein fraction having GGT activity and its production was suppressed
      by a GGT inhibitor. Furthermore, the production of GSAMC from allicin and
      GSAC/GS1PC was found in another model reaction. The reaction between allicin and
      GS1PC was faster than that between allicin and GSAC and, thus, may be involved in
      the production of GSAMC in the early stage of the aging process.

PMID- 30226991
TI  - Impact of the Coordinated Approach to Child Health Early Childhood Program for
      Obesity Prevention among Preschool Children: The Texas Childhood Obesity Research
      Demonstration Study.
AB  - BACKGROUND: This study presents the impact of a 2-year implementation of
      Coordinated Approach to Child Health Early Childhood (CATCH EC), a preschool
      based healthy nutrition and physical activity program, on child BMI z-scores, BMI
      percentiles, diet, physical activity, and sedentary behaviors among 3- to 5-year
      old children across Head Start centers in Houston and Austin, Texas. METHODS: We
      used a quasi-experimental study design with serial cross-sectional data
      collection (Intervention catchment area: n = 12 centers, 353 parent-child dyads
      in Year 1; n = 12 centers, 365 parent-child dyads; Comparison catchment area: n =
      13 centers in year 1, 319 parent child dyads; and n = 12 centers, 483 parent
      child dyads in year 2). Child height and weight were measured and parent self
      report surveys were conducted at year 1 (fall 2012) and year 2 (spring 2014).
      RESULTS: In year 1, 34.8% of the children were overweight or obese, 74% were
      Hispanic, and >80% reported an annual household income of <$25,000. In year 2,
      32.2% were overweight or obese, 72% were Hispanic, and 82.3% reported an annual
      income of <$25,000. Results demonstrated significantly lower child BMI z-scores
      [beta = -0.26 (95% confidence interval, CI: -0.50 to -0.01), p = 0.041] and BMI
      percentiles [beta = -6.5 (95% CI: -12.4 to -0.69), p = 0.028] from year 1 to 2
      follow-up among those in intervention Head Start centers, compared to those in
      the comparison centers. There were no significant between-group changes in child
      dietary, physical activity, or screen time behaviors. CONCLUSION: Implementation
      of a preschool-based obesity prevention program can be modestly effective in
      lowering the prevalence of child overweight in low-income populations.

PMID- 30226992
TI  - When Do Patients Improve After Hip Arthroscopy for Femoroacetabular Impingement?
      A Prospective Cohort Analysis.
AB  - BACKGROUND:: Hip arthroscopy for femoroacetabular impingement (FAI) has been
      shown to improve patient outcomes, especially for returning to sport. Although
      previous studies often evaluated outcomes 2 years after hip arthroscopy, there
      has been no analysis of the progression of patient improvement over time or with
      respect to achieving the minimal clinically important difference (MCID).
      HYPOTHESIS/PURPOSE:: The purpose was to prospectively evaluate changes in patient
      reported outcome (PRO) scores during the first 2 years after hip arthroscopy for
      FAI and to analyze when the MCID is achieved. It was hypothesized that clinically
      significant changes will be reached by 1 year after surgery. STUDY DESIGN:: Case
      series; Level of evidence, 4. METHODS:: Patients undergoing hip arthroscopy for
      FAI were prospectively enrolled, and they completed the 12-Item Short Form Health
      survey (SF-12), modified Harris Hip Score, and Hip disability and Osteoarthritis
      Outcome Score (HOOS) at preoperative baseline and 3 months, 6 months, 1 year, and
      2 years after surgery. Mean scores and the percentage of patients reaching the
      MCID at each time point were analyzed via analysis of variance and Cochrane
      Armitage trend tests. RESULTS:: A total of 129 hips from 122 patients were
      evaluated, revealing significant improvements after hip arthroscopy for FAI (PRO
      scores increased 19 to 45 points) with 95.8%, 93.6%, and 84.8% of patients
      achieving the MCID for HOOS-Sports, HOOS-Quality of Life (QoL), and HOOS-Pain,
      respectively, at 2-year follow-up. Analysis of PRO change showed that for all
      scores, the greatest improvement occurred from presurgery to postoperative 3
      months, with lesser improvements at subsequent 6-month, 1-year, and 2-year time
      points ( P < .001). The SF-12 physical component score, HOOS-Sports, and HOOS-QoL
      continued to show statistically significant improvements through 2 years, while
      other scores plateaued after 3 months. The percentage of patients achieving the
      MCID for HOOS-Sports, HOOS-QoL, and HOOS-Pain continued to increase over 2 years,
      but the percentage achieving the MCID did not increase after 3 months for all
      other scores. CONCLUSION:: Hip arthroscopy for FAI yields significant
      improvements in patient outcomes within 2 years of surgery. The majority of
      improvement occurs within 3 months after surgery, but certain outcomes, such as
      returning to sport, QoL, and pain, can continue to improve through 2 years.

PMID- 30226993
TI  - Associations between Childhood Weight Status and Timing of First Sex in an
      Ethnically Diverse Sample.
AB  - BACKGROUND: Most research linking weight status and timing of first sexual
      intercourse is cross-sectional in design, with few longitudinal analyses
      published to date. We examined associations between childhood weight status and
      subsequent onset of first sexual intercourse within a survival analytic
      framework, testing for differences among Hispanic, black, and white females and
      males. METHODS: Data were drawn from 6379 child respondents of the 1979 National
      Longitudinal Survey of Youth aged 13 and older at last assessment. Cox
      proportional hazards regression models were estimated predicting age at first
      sexual intercourse from weight status during childhood without and with
      adjustment for correlated risk factors. Analyses were conducted separately by sex
      and race/ethnicity, with interactions among weight status, respondent sex, and
      race/ethnicity modeled in subsidiary analyses. RESULTS: Overweight status
      predicted earlier sexual intercourse among Hispanic females, whereas obese status
      predicted delayed sexual intercourse among white males, both relative to peers of
      the same race/ethnicity with healthy weight. Underweight status predicted delayed
      sexual intercourse among Hispanic males relative to peers with healthy weight.
      Significant differences by sex and race/ethnicity were observed in tests of
      interactions. CONCLUSIONS: Findings document associations between childhood
      weight status and subsequent onset of first sexual intercourse, especially among
      Hispanic females and males and white males. Together, results highlight
      respondent sex and race/ethnicity as potential moderators and also unique risk
      for Hispanic females who were overweight as children, and who may benefit from
      early screening and education to delay sexual initiation to reduce risk of early
      unplanned pregnancy and sexually transmitted infections.

PMID- 30226994
TI  - Peripheral chemoreceptor deactivation attenuates the sympathetic response to
      glucose ingestion.
AB  - Acute increases in blood glucose are associated with heightened muscle
      sympathetic nerve activity (MSNA). Animal studies have implicated a role for
      peripheral chemoreceptors in this response, but this has not been examined in
      humans. Heart rate, cardiac output (CO), mean arterial pressure (MAP), total
      peripheral conductance (TPC), and blood glucose (BG) concentrations were
      collected in 11 participants. MSNA was recorded in a subset of 5 participants via
      microneurography. Participants came to the lab on two separate days (i.e. one
      control and one experimental day). On both days, participants ingested 75g of
      glucose following baseline measurements. On the experimental day, participants
      breathed 100% oxygen for 3 minutes at baseline and again at 20, 40, and 60 min
      post glucose ingestion to deactivate peripheral chemoreceptors. Supplemental
      oxygen was not given to participants on the control day. There was a main effect
      of time on blood glucose (P<0.001), heart rate (P<0.001), CO (P<0.001),
      sympathetic burst frequency (P<0.001), burst incidence (P=0.01), and total MSNA
      (P=0.001) for both days. Blood glucose concentrations and burst frequency were
      positively correlated on the control day (r=0.42; P=0.03) and experimental day
      (r=0.62; P=0.003). There was a time x condition interaction (i.e. normoxia vs.
      hyperoxia) on burst frequency, in which hyperoxia significantly blunted burst
      frequency at 20 and 60 min post glucose ingestion only. Given that hyperoxia
      blunted burst frequency only during hyperglycemia, our results suggest that the
      peripheral chemoreceptors are involved in activating MSNA post glucose ingestion.

PMID- 30226996
TI  - Insulin regulates GLUT4 in the Ventromedial Hypothalamus to Restore the
      Sympathoadrenal Response to Hypoglycemia in Diabetic Rats.
AB  - It is proposed that the impaired counterregulatory response (CRR) to hypoglycemia
      in insulin deficient diabetes may be due to chronic brain insulin deficiency. To
      test this hypothesis, streptozotocin-diabetic Sprague-Dawley rats were infused
      with either insulin (3mU/day) or artificial cerebrospinal fluid (aCSF)
      bilaterally into the ventromedial hypothalamus (VMH) for 2 weeks and compared to
      nondiabetic rats. Rats underwent hyperinsulinemic (50 mU.kg-1.min-1) hypoglycemic
      (~45 mg/dl) clamps. Diabetic rats demonstrated an impaired CRR to hypoglycemia
      noted by an high glucose infusion rate (GIR) and blunted epinephrine and glucagon
      responses. The defective sympathoadrenal response was restored with chronic
      infusion of insulin into the VMH. Diabetic rats had decreased VMH Akt
      phosphorylation and decreased VMH glucose transporter 4 (GLUT4) content, which
      was also restored with chronic infusion of insulin into the VMH. Separate
      experiments in non-diabetic rats in which VMH GLUT4 translocation was inhibited
      with an infusion of indinavir was notable for an impaired CRR to hypoglycemia
      indicated by increased GIR and diminished epinephrine and glucagon responses.
      Results suggest that in this model of diabetes, VMH insulin deficiency impairs
      the sympathoadrenal response to hypoglycemia and chronic VMH insulin infusion is
      sufficient to normalize the sympathoadrenal response to hypoglycemia, via
      restoration of VMH GLUT4 expression.

PMID- 30226995
TI  - Perceived Body Discrimination and Intentional Self-Harm and Suicidal Behavior in
      Adolescence.
AB  - BACKGROUND: This study examines whether discrimination based on the body is
      associated with intentional self-harm and suicidal behavior in adolescence.
      METHODS: Participants were from the Longitudinal Study of Australian Children (N
      = 2948; 48% female). Discrimination and items on self-harm and suicidal behavior
      were measured in the Wave 6 assessment, when study participants were 14-15 years
      old. BMI, depressive symptoms, peer victimization, and weight self-perception
      were also assessed. RESULTS: Discrimination was associated with increased risk of
      thoughts of self-harm (OR = 2.41, 95% CI = 1.88-3.10), hurting the self on
      purpose (OR = 2.27, 95% CI = 1.67-3.08), considering suicide (OR = 2.17, 95% CI =
      1.59-2.96), having a suicide plan (OR = 2.50, 95% CI = 1.81-2.47), attempting
      suicide (OR = 1.96, 95% CI = 1.30-2.96), controlling for sociodemographic
      factors, BMI, and depressive symptoms. These associations generally held
      adjusting for peer victimization or weight self-perception. CONCLUSIONS: Weight
      discrimination has been associated consistently with poor outcomes in adulthood.
      The present research indicates these associations extend to adolescence and an
      extremely consequential outcome: the social experience of weight increases risk
      of intentional self-harm and suicidal behavior.

PMID- 30226997
TI  - Contribution of Systemic Inflammation to Permanence of KATP-induced Neonatal
      Diabetes in Mice.
AB  - Gain-of-function (GOF) mutations in ATP-sensitive potassium (KATP) channel cause
      neonatal diabetes. Despite the well-established genetic root of the disease, the
      pathways modulating disease severity and treatment effectiveness remain poorly
      understood. Patient phenotypes can vary from severe diabetes to remission, even
      in individuals with the same mutation and within the same family; suggesting that
      subtle modifiers can influence disease outcome. We have tested the underlying
      mechanism of transient vs permanent neonatal diabetes in KATP-GOF mice treated
      for 14-days with glibenclamide. Some KATP-GOF mice show remission of diabetes and
      enhanced insulin sensitivity long-after diabetes treatment ended, compared with
      severely insulin-resistant non-remitting mice. However, insulin sensitivities are
      not different between the two groups before or during diabetes induction,
      suggesting that improved sensitivity is a consequence, rather than the cause of
      remission; implicating other factors modulating glucose early in diabetes
      progression. Leptin, glucagon, insulin and GLP-1 are not different between
      remitters and non-remitters. However, liver glucose production is significantly
      reduced before transgene induction in remitter, relative to non-remitter and non
      treated mice. Surprisingly, while subsequent remitter animals exhibited normal
      serum cytokines, non-remitter mice showed increased cytokines, which paralleled
      the divergence in blood glucose. Together, these results suggest that systemic
      inflammation may play a role in the transient vs permanent form of neonatal
      diabetes. Supporting this conclusion, treatment with the anti-inflammatory
      Meloxicam significantly increased the fraction of remitting animals. Beyond
      neonatal diabetes, the potential for inflammation and glucose production to
      exacerbate other forms of diabetes from a compensated state to a glucotoxic state
      should be considered.

PMID- 30226998
TI  - Engineering root microbiomes for healthier crops and soils using beneficial,
      environmentally safe bacteria.
AB  - The Green Revolution developed new crop varieties, which greatly improved food
      security worldwide. However, the growth of these plants relied heavily on
      chemical fertilizers and pesticides, which have led to an overuse of synthetic
      fertilizers, insecticides, and herbicides with serious environmental consequences
      and negative effects on human health. Environmentally friendly plant-growth
      promoting methods to replace our current reliance on synthetic chemicals and to
      develop more sustainable agricultural practices to offset the damage caused by
      many agrochemicals are proposed herein. The increased use of bioinoculants, which
      consist of microorganisms that establish synergies with target crops and
      influence production and yield by enhancing plant growth, controlling disease,
      and providing critical mineral nutrients, is a potential solution. The
      microorganisms found in bioinoculants are often bacteria or fungi that reside
      within either external or internal plant microbiomes. However, before they can be
      used routinely in agriculture, these microbes must be confirmed as nonpathogenic
      strains that promote plant growth and survival. In this article, besides
      describing approaches for discovering plant-growth-promoting bacteria in various
      environments, including phytomicrobiomes and soils, we also discuss methods to
      evaluate their safety for the environment and for human health.

PMID- 30226999
TI  - Sand bedding as a reservoir for Lactococcus garvieae dissemination in dairy
      farms.
AB  - Lactococcus garvieae is now recognized as a species with clinical significance
      for human and veterinary medicine. The aim of this study was to evaluate the
      presence of this pathogen in sand bedding and milk samples. Two farms in
      Minnesota with problems of clinical and subclinical mastitis due to streptococci
      like organisms were selected. Twenty-four Lactococcus garvieae isolates from sand
      bedding and 18 isolates from quarter milk were comparatively studied using a
      genotypic approach. RAPD (random amplification of polymorphic DNA) PCR and REP
      (repetitive element palindromic) PCR experiments highlighted a similar
      electrophoretic profile. When genes belonging to the core genome of L. garvieae
      were tested through a MLRT (multilocus restriction typing), we again observed
      that all L. garvieae isolates coming from sand bedding and milk shared a common
      profile, distinguishable from previously studied representative L. garvieae
      strains. These data indicate that the L. garvieae isolated from sand bedding and
      milk originated from a few strains adapted to persist in the same habitat. This
      supports the hypothesis that sand bedding can represent a reservoir of L.
      garvieae strains and be a potential vehicle for their dissemination in dairy
      farms.

PMID- 30227000
TI  - Efficacy of Injury Prevention Training Is Greater for High-Risk vs Low-Risk Elite
      Female Youth Soccer Players.
AB  - BACKGROUND:: The efficacy of robustness training for high- versus low-risk
      individuals within high-risk groups is currently unknown. PURPOSE:: To explore
      the efficacy of robustness training on injury risk factors among female youth
      soccer players and to examine if high-risk athletes are greater responders to
      such training. STUDY DESIGN:: Controlled laboratory study. METHODS:: A total of
      125 elite youth female soccer players on the English FA talent pathway were
      randomly selected into a training group (n = 71) or a control group (n = 54).
      Relative leg stiffness, 2-dimensional knee valgus and knee flexion range of
      motion from a single-legged countermovement jump, and probability of high knee
      abduction moment (pKAM) risk were all determined before and after a 16-week
      robustness training program. For further analysis, participants in the training
      group were split into groups based on risk: high risk (pKAM >0.80, n = 33) and
      low risk (pKAM <0.55, n = 33). Magnitude-based inferences were used to explore
      differences between the control and intervention groups and the high- and low
      risk groups. RESULTS:: Magnitude-based inferences demonstrated significant
      beneficial effects in the training group for knee valgus, pKAM, and leg stiffness
      as compared with the control group. The control group demonstrated possible
      worthwhile differences in knee flexion range of motion as compared with the
      intervention group. The high-risk group demonstrated likely/very likely
      worthwhile differences versus the low-risk group for all parameters.
      CONCLUSION/CLINICAL RELEVANCE:: Robustness training induces significant
      beneficial improvements in injury risk factors among female youth soccer players.
      The beneficial effects of this multidimensional program are greater for those
      classified as high risk.

PMID- 30227001
TI  - Quite a Third Birthday.

PMID- 30227002
TI  - CBER's Experience With Adaptive Design Clinical Trials.
AB  - There is considerable interest among pharmaceutical and other medical product
      developers in adaptive clinical trials, in which knowledge learned during the
      course of a trial affects ongoing conduct or analysis of the trial. When the FDA
      released a draft Guidance document on adaptive design clinical trials in early
      2010, expectations were high that it would lead to an increase in regulatory
      submissions involving adaptive design features, particularly for confirmatory
      trials. A 6-year (2008-2013) retrospective survey was performed within the Center
      for Biologics Evaluation and Research (CBER) at the FDA to gather information
      regarding the submission and evaluation of adaptive design trial proposals. We
      present an up-to-date summary of adaptive design proposals seen in CBER and
      provide an overview of our experiences. We share our concerns regarding the
      statistical issues and operational challenges raised during the review process
      for adaptive design trials. We also provide general recommendations for
      developing proposals for such trials. Our motivation in writing this paper was to
      encourage the best study design proposals to be submitted to CBER. Sometimes
      these can be adaptive, and sometimes a simpler design is most efficient.

PMID- 30227003
TI  - Comparative Analysis Between the Top-Selling Drugs in the Japanese Pharmaceutical
      Market and Those in the United States, the United Kingdom, France, and Germany.
AB  - BACKGROUND: Japan is currently the second largest pharmaceutical market in the
      world, and Japanese pharmaceutical companies are actively seeking to identify
      assets in other countries. An affluent population provides ample opportunity for
      pharmaceutical companies to develop within Japan; however, given its weak
      macroeconomic foundation, Japan is currently seeking to cut costs through the use
      of more generic drugs and lower prices. Nevertheless, no detailed empirical
      analyses regarding how Japanese companies can expand their global presence while
      ensuring domestic sales, or what opportunities lie ahead for global companies
      planning to enter the Japanese market, have been conducted. To our knowledge,
      this is the first study to provide statistical evidence regarding characteristics
      of the Japanese market. METHODS: The data set for this study was the most recent
      list of the 100 top-selling drugs globally and in Japan, the United States, the
      United Kingdom, France, and Germany. The data were obtained from the IMS Japan
      Pharmaceutical Market database. RESULTS: More cardiovascular and less central
      nervous system (CNS) and oncology drugs were ranked among the top 100 best
      selling drugs in the Japanese market; however, the promotion of CNS and oncology
      drug development was evident, and competition from generic drugs was shown to
      have eroded, especially in therapeutic areas with no assured benefits in the
      global market, such as with cardiovascular drugs. CONCLUSIONS: These results
      suggest that the Japanese market will rival overseas markets in the near future.
      Pharmaceutical companies should seriously consider operating within Japan, whose
      market is currently transitioning to a global market.

PMID- 30227004
TI  - Validation of Prognostic Marker Tests: Statistical Lessons Learned From
      Regulatory Experience.
AB  - Despite concerted efforts to discover and validate prognostic biomarkers or
      signatures, few medical tests indicated for prognostic uses have been widely
      accepted by the clinical community. Even fewer, perhaps, are covered by public or
      private health plans. We were able to identify 6 prognostic marker tests that
      have been approved or cleared by the US Food and Drug Administration. The pivotal
      clinical studies for these prognostic marker tests exhibited a wide variety of
      designs and statistical analyses. From these experiences, we develop statistical
      points to consider for design, conduct, and analysis of successful clinical
      validation studies of prognostic tests. In particular, we review broad themes
      regarding prospective and retrospective study designs, sample size, clinical
      performance evaluation, and handling of missing data. Our review emphasizes the
      distinction between a prognostic biomarker and the medical test used to measure
      it. For this purpose, a section on test measurement validation is also provided.

PMID- 30227005
TI  - Statistical Monitoring in Clinical Trials: Best Practices for Detecting Data
      Anomalies Suggestive of Fabrication or Misconduct.
AB  - BACKGROUND: Traditional site-monitoring techniques are not optimal in finding
      data fabrication and other nonrandom data distributions with the greatest
      potential for jeopardizing the validity of study results. TransCelerate BioPharma
      conducted an experiment testing the utility of statistical methods for detecting
      implanted fabricated data and other signals of noncompliance. METHODS:
      TransCelerate tested statistical monitoring on a data set from a chronic
      obstructive pulmonary disease (COPD) clinical study with 178 sites and 1554
      subjects. Fabricated data were selectively implanted in 7 sites and 43 subjects
      by expert clinicians in COPD. The data set was partitioned to simulate studies of
      different sizes. Analyses of vital signs, spirometry, visit dates, and adverse
      events included distributions of standard deviations, correlations, repeated
      values, digit preference, and outlier/inlier detection. An interpretation team,
      including clinicians, statisticians, site monitoring, and data management,
      reviewed the results and created an algorithm to flag sites for fabricated data.
      RESULTS: The algorithm identified 11 sites (19%), 19 sites (31%), 28 sites (16%),
      and 45 sites (25%) as having potentially fabricated data for studies 2A, 2, 1A,
      and 1, respectively. For study 2A, 3 of 7 sites with fabricated data were
      detected, 5 of 7 were detected for studies 2 and 1A, and 6 of 7 for study 1.
      Except for study 2A, the algorithm had good sensitivity and specificity (>70%)
      for identifying sites with fabricated data. CONCLUSIONS: We recommend a cross
      functional, collaborative approach to statistical monitoring that can adapt to
      study design and data source and use a combination of statistical screening
      techniques and confirmatory graphics.

PMID- 30227006
TI  - Profit Evaluations When Adaptation by Design Is Applied.
AB  - BACKGROUND: Adaptation by design consists in conservatively estimating the phase
      III sample size on the basis of phase II data; it is also called conservative
      sample size estimation (CSSE). The usual assumptions are that the effect size is
      the same in both phases and that phase II data are not used for phase III
      confirmatory analysis. CSSE has been introduced to increase the rate of
      successful trials, and it can be applied in most clinical areas. CSSE reduces the
      probability of underpowered experiments and can improve the overall success
      probability of phase II and III, but it also increases phase III sample size,
      increasing the time and cost of experiments. Thus, the balance between higher
      revenue and greater cost is the issue. METHODS: A profit model was built assuming
      that CSSE was applied and considering income per patient, annual incidence, time
      on market, market share, phase III success probability, fixed cost of the 2
      phases, and cost per patient under treatment. RESULTS: Profit turns out to be a
      random variable depending on phase II sample size and conservativeness. Profit
      moments are obtained in a closed formula. Profit utility, which is a linear
      function of profit expectation and volatility, is evaluated in accordance with
      the modern theory of investment performances. Indications regarding phase II
      sample size and conservativeness can be derived on the basis of utility, for
      example, through utility optimization. CONCLUSIONS: CSSE can be adopted in many
      different statistical problems, and consequently the profit evaluations proposed
      here can be widely applied.

PMID- 30227007
TI  - Who Said It Better? A Test of Wording Differences in the MedWatch "Toll-Free
      Statement" for Consumer Reporting of Side Effects in Direct-to-Consumer
      Television Advertisements.
AB  - BACKGROUND: A toll-free statement alerting consumers how to report side effects
      to the US Food and Drug Administration (FDA) is required for both prescription
      drug labeling and direct-to-consumer (DTC) print ads. Because of different
      regulatory requirements between these materials (the Toll-free Number for
      Reporting Adverse Events on Labeling for Human Drug Products Rule [TFNR] versus
      the FDA Amendments Act [FDAAA], respectively), the wording of this statement
      differs. We studied how statement wording for reporting side effects to FDA in
      DTC television ads affects comprehension of product risks and benefits,
      comprehension of and memory for the toll-free statement, and perceived statement
      clarity. METHODS: Participants viewed 1 of 8 mock prescription drug television
      ads that varied the wording and placement of the toll-free statement, and then
      responded to a questionnaire. RESULTS: The FDAAA statement was more noticeable,
      clear, and more participants were able to recall and recognize its correct
      purpose. Comprehension of product risk and benefit information did not differ
      based on statement wording. CONCLUSIONS: Findings suggest that the FDAAA toll
      free statement wording is superior to that of the TFNR.

PMID- 30227008
TI  - The Score Card Approach: A First Step Toward an Evidence-based Differentiation
      Assessment for Tablets.
AB  - BACKGROUND: The differentiation of tablets by their physical appearance is a
      contributing factor to the safe use of medications. In this study, a "score card"
      was developed to assess how well one tablet is differentiated from another tablet
      on the basis of the physical attributes of color, size, and shape. METHODS: The
      score card was derived from a "2-out-of-5" difference test, in which participants
      were presented with groups of 5 tablets with varying color, size, and shape, and
      were asked to identify the 2 tablets that were different from the other 3
      tablets. RESULTS: Based on the study results (ie, recognition rate of the
      differences in the tablets, and confidence in such recognition), simplified
      metrics were derived to "score" a comparison of 2 tablets differing in color,
      size, and/or shape. The higher the score, the better the 2 tablets could be
      visually distinguished from each other. The scores were ranked as representing
      "strong," "moderate," or "weak" differentiation, with a corresponding stoplight
      color code, to create the final score card. The score card was internally
      verified by applying it to the tablets used in the study, then to the multiple
      strengths of Gilotrif(r) (afatinib) tablets, a Boehringer Ingelheim approved drug
      product. CONCLUSION: The score card is a first step in the assessment of adequate
      differentiation of tablets and can be used for the design of tablets that promote
      safe use of medication.

PMID- 30227009
TI  - Pharmaceutical Pricing Policies and Procedures in Saudi Arabia: A Narrative
      Review.
AB  - From inception, the health care system in Saudi Arabia has ensured the
      availability of health care facilities to its people. This article discusses the
      pharmaceutical pricing policies and the impact of health drug prices on the
      public in the Kingdom of Saudi Arabia. A review of government and Saudi Food and
      Drug Authority (SFDA) policy documents, guidelines, and articles published in
      PubMed and other indexed journals (N = 10) was performed to identify the relevant
      literature. Results showed that the government appears poised and focused on the
      availability of better health care facilities to the Saudi population. The
      pharmaceutical market in Saudi Arabia commands a large portion of the
      pharmaceuticals market share in the entire Middle East region. The government,
      through the SFDA, sets the prices of pharmaceutical products. There are
      occasional price variations, which are induced by a number of factors. However,
      because the Saudis enjoy free health care coupled with the recent introduction of
      a compulsory health insurance policy, the impact of price variation is not felt.
      In addition, the Saudis prefer using branded medicines. The SFDA plays a major
      role in price regulation by setting up rules for pharmaceutical product pricing.
      However, there appears to be little or no impact of pharmaceutical price
      variation in Saudi Arabia because of better earning power among the population
      and free health care access to public health facilities.

PMID- 30227010
TI  - Community Opinions on the Collection and Use of Historical Control Data in
      Nonclinical Toxicity Studies.
AB  - BACKGROUND: Access and use of historical control data was identified as a top
      stakeholder concern across organizations according to results of a survey of
      needs and challenges related to nonclinical data conducted by the FDA/PhUSE
      Nonclinical Working Group in 2011. There is a perception there may be additional
      ways to capitalize on historical control data to enhance studies or submissions
      across industry, academia, and government. During the working sessions of the
      FDA/PhUSE Computational Sciences Symposium in March 2012, a Historical Control
      subgroup of the FDA/PhUSE Nonclinical Working Group was formed to investigate how
      the industry might more effectively harness the vast amount of data from
      untreated/vehicle control animals. The subgroup includes broad representation of
      stakeholders with interest in nonclinical data. METHODS: This paper describes
      progress to date and includes results of a second survey to determine how
      organizations use and would like to use historical control data. RESULTS:
      Respondents to the survey strongly support that historical control data are
      useful and should be in an accessible format. Four potential project options were
      posed in the survey, with an overall positive response; also, several write-in
      options were suggested by respondents. CONCLUSIONS: Community-supported projects
      to increase the availability of well-annotated and scientifically curated
      collections of historical control data appear to be of most interest.

PMID- 30227011
TI  - Statistical Analysis of Cumulative Serious Adverse Event Data From Development
      Safety Update Reports.
AB  - BACKGROUND: Monitoring safety in clinical trials by regulatory authorities and
      sponsors involves the clinical review, often subjectively, of large data sets of
      different types of safety information which may require considerable resources.
      METHODS: This study investigated a means of statistically guided clinical review
      of safety data provided in the Cumulative Table of Serious Adverse Events of a
      Development Safety Update Report (DSUR). A simple statistical approach that
      treats every adverse event as independent of all others and uses a reference
      prior, which avoids infinite estimates of relative risk but does not unduly
      influence posterior inferences, was used with fixed rules of relative risk to
      identify a serious adverse event preferred term as a potential risk. RESULTS:
      This simple model, using cumulative serious adverse event (SAE) data from 5
      DSURs, identified a small group of potential risks that included some not
      reported by the sponsor as well as most of those reported by the sponsor in the
      DSUR Summary of Important Risks. CONCLUSIONS: The method provides a systematic
      and objective approach to analysis of cumulative SAE data that could help to
      identify potential risks that need further investigation by a regulatory
      authority or sponsor.

PMID- 30227013
TI  - Maintaining the Highest Ethical Standard in Publishing.

PMID- 30227012
TI  - Evaluation of Safety Profiles of Blood Cancer Drugs Approved in Japan.
AB  - BACKGROUND: In drug development, the safety of a test drug for human use is first
      assessed in animal toxicology studies; therefore, the no-observed-adverse-effect
      level (NOAEL) and toxicokinetic data are very important for the evaluation of
      clinical safety. The ratio of drug exposure in animals at the NOAEL to that of
      humans at the expected therapeutic dose is one of the primary measures for
      determining the risk-benefit profile of a pharmaceutical. The objective of this
      study was to evaluate the safety profiles of drugs for blood cancer approved in
      Japan by examining safety indices (SIs). METHODS: SIs were calculated as animal
      to-human ratios in doses and exposure using NOAEL, severely toxic dose 10% of the
      animals, highest nonseverely toxic dose, maximum approved dose, and exposure
      levels (Cmax and area under the curve [AUC]) at the NOAEL and maximum approved
      dose. If the SI of a certain drug is <1.0, either the maximum therapeutic dose
      exceeds the NOAEL, or the exposure level at the maximum therapeutic dose exceeds
      the exposure level at the NOAEL. RESULTS: A total of 8 of 17 SIs by dose were
      <1.0; 6 of 8 SIs by Cmax were <1.0, and 6 of 9 SIs by AUC were <1.0. CONCLUSIONS:
      In cases where the SI is <1.0, no drug safety margin can be assured based on
      animal data. When extrapolating data from animal studies to safety assessment in
      clinical studies, safety profile would be one of aspects to be carefully
      considered in drug development, including postmarketing surveillance.

PMID- 30227014
TI  - Institutional Review Boards as Arbiters of Expanded Access to Unapproved Drugs:
      Time for a Change?
AB  - Institutional review boards (IRBs) are one of the bodies charged with
      prospectively reviewing compassionate use, the hopefully therapeutic use of an
      unapproved drug in a seriously ill or dying patient who has no other treatment
      options. However, there are ethical issues in assigning this role to a body whose
      primary purpose is to review research proposals. The role of IRBs with regard to
      compassionate use must be examined and potentially revised.

PMID- 30227015
TI  - Regulatory System Changes in Russia: A Historical Review and Future Perspectives.
AB  - The Russian pharmaceutical market is expected to grow and attract foreign
      investors. Nevertheless, the frequent changes in regulatory legislation make the
      process of marketing authorization in Russia much more challenging than in
      Europe. In the present review, an insight into the practical issues caused by the
      implementation of the new marketing authorization law from 2010 until now is
      provided. The outcome of the new law application is contrary to the old one from
      1998, which was amended once in 2000. To date, it has already been revised 19
      times. The reasons for the frequent amendments as well as future perspectives are
      provided.

PMID- 30227016
TI  - An Overview of the Regulatory and Developmental Strategies of Chronotherapeutics.
AB  - The pivotal idea toward the development of chronotherapeutics is synchronizing
      the in vivo drug bioavailability with the rhythms of the disease to optimize
      therapeutic outcomes and minimize side effects, which is contrary to the
      homeostatic theory of drug delivery. The advent of formulation technologies,
      marketing exclusivities of innovative products, and provisions/amendments in
      regulatory frameworks have led to the development of commercial chronotherapeutic
      products, but their numbers are few and are confined mainly to diseases of the
      cardiovascular system. A major bottleneck for its development would be the
      understanding of rhythmic variations of disease, but following regulatory
      pathways for commercial development has always been challenging. In this article,
      a few commercial products have been investigated in view of their developmental
      strategies in order to find out the minimum preclinical and clinical studies
      needed for the development of chronotherapeutics.

PMID- 30227017
TI  - Process Innovation Improves Trial Operation Efficiency.
AB  - BACKGROUND: Despite the fact that unaddressed delays in clinical trial operation
      could severely compromise the overall effort invested, there seems to be a lack
      of concerted effort in reforming such delays. This study evaluated the composite
      effect of initiatives in reforming trial operation efficiency. METHODS: A high
      volume academic medical center in Korea has implemented various initiatives to
      improve the trial operation efficiency by expediting times from institutional
      review board (IRB) submission to approval, from IRB submission to trial open for
      subject enrollment, and from trial open to first patient-in. The initiatives
      include implementation of the protocol preliminary review, parallel processing of
      the clinical trial agreement review in line with the protocol submission to the
      IRB, and involvement of project manager for operational risk management. Times
      from IRB submission to approval, from IRB submission to trial open, and from
      trial open to first patient-in before and after implementation of initiatives
      were compared. RESULTS: The median time required in IRB approval was meaningfully
      shorter in the postinitiative group (19 vs 14 days; P < .001). The median times
      from IRB submission to trial open for subject enrollment and from trial open to
      first patient-in were reduced significantly in the postinitiative group (trial
      open: 25 vs 18 days, P < .001; first patient-in: 111.5 vs 100 days, P = .014).
      CONCLUSIONS: The initiatives were effective in reforming trial operational
      efficiency. Additional studies to address the cause of operational delay and
      modifiable factors influencing subject enrollment are needed to further improve
      operational efficiency.

PMID- 30227018
TI  - Applicability of Selective Data Collection to Cancer Clinical Studies for
      Supplemental Marketing Approvals: Frequency of Adverse Reactions Observed During
      Supplemental Approval Compared With First Approval.
AB  - BACKGROUND: In 2012, the US Food and Drug Administration (FDA) issued the draft
      guidance "Determining the Extent of Safety Data Collection Needed in Late Stage
      Premarket and Postapproval Clinical Investigations." The selective data
      collection approach proposed in this guidance leads to reductions in costs and
      work time and may improve the quality of the database for clinical trials. The
      current study evaluated the applicability of selective data collection for
      oncology drugs. METHODS: The labeling information of oncology drugs obtained
      supplemental approvals from the FDA between 2005 and 2014 were used. The
      frequency of adverse reactions observed in clinical trials between the first
      approval and supplemental approvals of a specific drug were compared. Paired
      studies were categorized into the following 4 groups: A, same tumor type and same
      usage; B, same tumor type and different usage; C, different tumor type and same
      usage; D, different tumor type and different usage. RESULTS: A total of 46 study
      pairs for additional drug indications were investigated. In group A, 6 of the 7
      pairs showed a high correlation coefficient ( r = 0.988, 0.953, 0.947, 0.935,
      0.853, and 0.846). CONCLUSIONS: Selective data collection should be adopted in
      cases in which the additional indication of a drug is for the same tumor type and
      usage as the first or previous indication.

PMID- 30227019
TI  - Consumer Opinions on Existing and Proposed Australian Over-the-Counter Medicine
      Labeling Strategies in Comparison With the Standardized US Drug Facts Label.
AB  - BACKGROUND: With common over-the-counter (OTC) medication use, OTC labels as
      medicine information sources must be of high quality and usability. Standardized
      OTC labeling has been proposed in Australia using the Medicine Information Box
      (MIB), modeled on the US Drug Facts label. However, limited research has explored
      consumer opinions on existing nonstandardized Australian OTC, US Drug Facts, and
      proposed MIB labels. Therefore, this study aimed to explore consumer opinions on
      all 3 groups of OTC labels. METHODS: Three focus groups (N = 21 participants)
      were conducted in Sydney, Australia. Participants were shown existing Australian
      OTC labels, US Drug Facts labels, and mock MIB formats based on the Australian
      Therapeutic Goods Administration proposal. Discussions were audio recorded,
      transcribed verbatim, and thematically analyzed. RESULTS: Participants expressed
      varying opinions regarding existing nonstandardized Australian OTC labels'
      content and design, from acknowledgment of positive aspects (clear headings,
      relevant content) to decreased perceived readability (suboptimal color use, font
      size) and content discrepancies. Participants identified key Drug Facts and MIB
      label characteristics that contributed to perceived usability and format clarity
      (good headings, black-and-white format). Many preferred the Drug Facts label
      because of its greater perceived clarity and usability. Missing content (inactive
      ingredients, further contact details) were identified and consequently became
      opportunities for MIB improvement. CONCLUSIONS: Most participants seemed to
      prefer the US Drug Facts label, partly because of its perceived completeness.
      These findings suggest further improvements for the proposed MIB as a step toward
      Australian OTC label standardization.

PMID- 30227020
TI  - Mobile Nurse Services in Clinical Trials: Usage and Industry Perceptions.
AB  - BACKGROUND: With the pharmaceutical industry's increased attention on enhancing
      patient experiences during their participation in clinical trials, the use of
      mobile nurse (MN) services to support the conduct of clinical trial assessments
      in the home (or in alternative locations other than in investigational sites) has
      been gaining momentum. METHODS: Because no quantitative data capturing industry
      wide practices are available, in July 2014, Tufts Center for the Study of Drug
      Development and Hoffman-La Roche conducted an online survey to gather data on the
      prevalence and utilization of MN services in clinical trials taking into account
      the following factors: industry perceptions of the business model, risks barriers
      to adoption, vendor landscape, cost, and prospects for future growth. A total of
      113 respondents answered the survey, with 53 respondents answering all questions.
      RESULTS: The use of MN services in clinical trials is an established and growing
      business practice. Utilization of MN services has so far been most prevalent in
      North America, followed by Western Europe. Sponsor companies that have adopted
      this model have done so mainly to improve patient retention and protocol
      compliance, as well as improve access to rare patients. Most of the companies
      surveyed work directly with vendors specializing in home nurse services.
      Experience with vendors was considered favorable in most cases. CONCLUSIONS:
      Building effective partnerships with 1 to 2 vendors is considered a key factor
      for long-term success.

PMID- 30227021
TI  - Reporting Adverse Drug Reactions in Product Labels.
AB  - Product labels are intended to provide health care professionals with clear and
      concise prescribing information that will enhance the safe and effective use of
      drug products. In this manuscript, we offer suggestions to improve product
      labels. First, we recommend that product labels that include comparator data be
      changed to include adjusted incidence proportions (or adjusted incidence rates
      when needed and appropriate) for adverse drug reactions that are somewhat common.
      Second, we believe that including comparator incidence in product labels is a
      good practice, as it gives health care providers and patients appropriate
      information to put the absolute risks in perspective. Finally, we recommend
      changing the practice of reporting extremely rare events based on the "Rule of 3"
      in the Summary of Product Characteristics in Europe. We recommend that these
      adverse drug reactions be put in a separate table from other adverse drug
      reactions with a note that it is difficult to reliably estimate their incidences.
      In exceptional circumstances, it may be possible to present an estimate of their
      incidence based on postmarketing data. We believe the proposed changes could help
      product labels to better reflect the risk of a drug relative to a comparator.

PMID- 30227022
TI  - The Impact of Protocol Amendments on Clinical Trial Performance and Cost.
AB  - BACKGROUND: Tufts Center for the Study of Drug Development (Tufts CSDD), in
      collaboration with 15 pharmaceutical companies and contract research
      organizations, gathered data on substantial global protocol amendments to better
      understand how to manage and to reduce the significant unplanned expense and
      delays associated with major changes to finalized protocol designs. METHODS: Data
      from 836 phase I-IIB/IV protocols were analyzed to understand amendment
      prevalence. Impact assessments were based on data from 136 randomly selected
      amendments. Data from 52 protocols were analyzed to derive estimates of the
      direct cost to implement amendments. RESULTS: Tufts CSDD found that 57% of
      protocols had at least one substantial amendment, and nearly half (45%) of these
      amendments were deemed "avoidable." Phase II and III protocols had a mean number
      of 2.2 and 2.3 global amendments, respectively. Protocols with one or more global
      amendments tended to be larger in scope, with longer patient recruitment
      durations and overall study durations compared with those without a global
      amendment. Protocols with at least one substantial amendment had fewer actual
      screened and enrolled patients relative to the original baseline plan than did
      those protocols without an amendment. The median direct cost to implement a
      substantial amendment was US$141,000 for a phase II protocol and $535,000 for a
      phase III protocol. CONCLUSIONS: The study findings provide insights into
      optimizing development planning, protocol design, and clinical trial management
      practices.

PMID- 30227023
TI  - Use of Medical Mobile Applications Among Hospital Pharmacists in Malaysia.
AB  - BACKGROUND: Handheld computers (HHCs) such as smartphones and tablets are
      providing a variety of drug information (DI) applications to assist pharmacists'
      decision making in the clinical and hospital setting. However, little is known
      about the extent of their use among Malaysian pharmacists. The current study
      aimed to assess the use of electronic DI resources via HHCs by pharmacists in
      Malaysia. This study also aimed to investigate the pharmacists' perception toward
      the DI content and functions of mobile medical applications. METHODS: A
      convenience sampling method was adopted to invite pharmacists (N = 450) working
      in various sectors such as hospitals, the drug approval authority, and academia
      to participate in this online survey. A 36-item questionnaire was administered,
      and data were summarized and presented using descriptive statistics. RESULTS: The
      response rate to this survey was 49.8% (n = 224). Overall, 213 respondents
      (95.1%) were active HHCs users in their daily clinical practice. About 194
      respondents (86.6%) disclosed that they often use HHCs for searching DI. Dosage
      recommendations (n = 198; 88.4%), adverse drug reactions (n = 153; 68.3%), and
      drug interactions (n = 146; 65.2%) were the most common DI retrieved. Meanwhile,
      general dosage recommendation, pediatric dosage recommendations and dosage
      recommendations for renal failure were ranked as the most important DI in mobile
      medical applications. Gaining access to the latest information on drugs and
      clinical practice were regarded as the most important functions of the mobile
      medical app. CONCLUSIONS: The use of HHCs for DI among pharmacists in Malaysia
      was high. The use of locally produced DI sources is still low compared to
      overseas sources. The most popular applications used for drug-related medical
      information were Micromedex, followed by Lexicomp and Medscape.

PMID- 30227024
TI  - Quality of Regulatory Decision-Making Practices: Issues Facing Companies and
      Agencies.
AB  - BACKGROUND: The science of decision making is well established, although in
      reality it is a mixture of science and art. What is currently lacking is research
      into decision making in medicines research and development. The aims of this
      study were to determine the current decision-making practices and methodologies
      for measuring the quality of the decision making and the barriers and solutions
      for making quality decisions within pharmaceutical companies and regulatory
      agencies. METHODS: Two analogous questionnaires were developed for use in this
      study. Fourteen agencies and 25 companies were asked to complete the
      questionnaire, assessing their decision making for submitting or approving a new
      drug application. RESULTS: The 68% and 71% response rate from companies and
      agencies, respectively, suggests interest in this topic, but the area is largely
      unexplored within the pharmaceutical environment. Moreover, all companies and 90%
      of the agencies believed that decision making at their organizations could be
      improved. Although both stakeholders have, to some extent, already implemented
      frameworks and various methodologies, these are often informal and unsystematic.
      Challenges remain and there is a need to change the organizational culture by
      increasing the awareness of the quality aspect in decision making. CONCLUSIONS:
      The findings of this study support the need to further characterize and assess
      the practices and behaviors of individuals and organizations. Furthermore, the
      barriers, mainly relating to the influence of biases, should be addressed by
      developing the general principles of a formal quality decision framework and
      identifying quality decision-making practices in order to ensure that structured
      decisions are made throughout the life cycle of medicines.

PMID- 30227025
TI  - TransCelerate's Clinical Quality Management System: From a Vision to a Conceptual
      Framework.
AB  - The Quality Management System (QMS) initiative of TransCelerate BioPharma Inc has
      identified potential benefits that could be captured from the development of a
      flexible, proactive clinical QMS conceptual framework for clinical research. Such
      a framework would aid organizations in seamlessly managing the complex clinical
      trial environment and, ultimately, in expediting delivery of needed treatments to
      patients. This article chronicles the evolution of a TransCelerate concept paper
      describing a proposed clinical QMS framework and reviews feedback from varied
      global clinical trial stakeholders during socialization of the concept paper.
      Many stakeholders recognized the potential for the concept paper to inform
      development of a harmonized International Council for Harmonisation (ICH)
      guideline, providing needed clarity from regulators on their expectations for QMS
      in the clinical realm. Accordingly, the article also describes TransCelerate's
      efforts to work with regulators to facilitate harmonization on this important
      topic and reviews ongoing work to develop additional tools and resources that may
      support organizations in evaluating whether and how they might translate the
      conceptual framework principles into practice.

PMID- 30227027
TI  - Using Contour Plots to Assess the Sensitivity of Clinical Trial Design
      Assumptions.
AB  - BACKGROUND: Sample size calculations are an important part of the design of any
      clinical trial. These calculations ensure a sufficient number of patients to
      detect a clinically meaningful difference between 2 treatments with high
      probability (ie, power). Perhaps less-often discussed, the sample size exercise
      is important so that resources are not wasted studying too many observations to
      test a particular hypothesis. Since patients may be randomized to doses of a
      novel treatment with a limited safety profile, or a placebo which provides no
      therapeutic benefit, sample size calculations in clinical trials come with an
      ethical burden not experienced in many subject-matter areas. METHODS: The sample
      size of a clinical trial should be determined using as much data as is available,
      over a range of assumptions, and with input from clinical colleagues. Graphical
      techniques are often utilized to summarize power and sample size calculations. In
      this manuscript, we propose the use of contour plots to better assess, report,
      and communicate the sensitivity of clinical trial design assumptions. RESULTS:
      Through several examples, we illustrate that contour plots are applicable to
      binary, continuous, and time-to-event endpoints for a variety of study design
      scenarios. CONCLUSIONS: Contour plots are a useful tool for the study team in
      designing clinical trials, and they can be included in study documents to better
      communicate the rationale for sample size for clinicians and regulators. Contour
      plots provide greater transparency as to the uncertainty of the currently
      available information, and can be useful in deciding whether to consider adaptive
      designs.

PMID- 30227026
TI  - Best Practices for Improving the Quality of Individual Case Safety Reports in
      Pharmacovigilance.
AB  - BACKGROUND: The quality of individual case safety reports (ICSRs) plays a vital
      role in identifying new safety signals in pharmacovigilance. This article focuses
      on establishing a method for ensuring the quality data. OBJECTIVE: To develop an
      in-house method for assessing the documentation grading and completeness score of
      ICSRs. METHODS: In the proposed method, 16 parameters, from report title to case
      narrative, are adopted to assess the quality of ICSRs. The in-house method
      ensures the completeness of the data and enhances the quality of ICSRs. RESULTS:
      The in-house method was found effective in calculating the completeness score of
      ICSR ranges from 0.05 to 1. Indian ICSR completeness scores significantly
      improved after the implementation of the proposed method in the third quarter of
      2013. In 2014 and until the third quarter of 2015, the score was found to be 0.91
      and 0.93 out of 1, respectively. CONCLUSION: The higher quality ICSRs aids in
      more effective identification of new drug safety alerts and provides evidence
      based information for regulating the drug safety.

PMID- 30227028
TI  - New Horizons in Pediatric Drug Development.

PMID- 30227029
TI  - iCAN: Providing a Voice for Children and Families in Pediatric Research.
AB  - Research and innovation are critical to improving the health and well-being of
      the world's children; clinical trials yield important information on a medical
      product's safety, dosing, and effectiveness. While the prescribing information
      available to pediatric providers has substantially improved, approximately 50% of
      medicines still do not have data on their labels to guide their appropriate use
      in children. Regulatory bodies have recently taken measures to ensure, if drugs
      have a potential pediatric indication, that the safety and efficacy clinical
      trials include the pediatric population. However, there are significant
      challenges with pediatric trials, including study design and feasibility,
      suitable formulations, and patient recruitment and retention. The authors propose
      that these challenges can be addressed by actively involving young people and
      families in study design so their insights can inform successful trial
      implementation. As the volume of pediatric research increases, there needs to be
      a concomitant effort for researchers and providers to seek input from patients
      and families in the development of their work, which can lead to a transformation
      of the cultural and regulatory environment of pediatric medicine. The benefits of
      patient and public involvement in research have been well documented. In 2006,
      the National Institute for Health Research Clinical Research Network: Children
      started its first Young Persons' Advisory Group in an effort to include young
      people in the design and delivery of pediatric research. Since their initial
      efforts, the youth advisory concept has grown into a global effort known as the
      International Children's Advisory Network (iCAN). This article describes the
      foundational building blocks of iCAN and provides tools to investigators and
      practitioners in an effort to increase the instances of children and families
      being invited to share their unique point of view in medicine.

PMID- 30227030
TI  - Bowel Preparations for Colonoscopy: A Regulatory Perspective.
AB  - Agents indicated for cleansing of the colon as a preparation for colonoscopy
      (bowel preps) are among the most frequently prescribed drugs for otherwise
      healthy patients. Better bowel preparation has been shown to translate into
      higher adenoma detection rates. Therefore, safety and efficacy standards need to
      be high. Clinical trials can be designed to show superiority or non-inferiority,
      and there are 3 different types of relevant New Drug Applications. Current
      endpoint instruments rely on clinician reporting, and more than 1 endpoint
      instrument may be required to ensure a valid appraisal of efficacy. Future trials
      that study hard-to-prepare patients and populations who are potentially at higher
      risk for adverse events (eg, those with renal dysfunction) would be of interest.
      Orthostatic hemodynamic changes with bowel preps as a drug class occur more
      frequently than previously recognized, and this also deserves further study.

PMID- 30227031
TI  - Applying Regulatory Science to Develop Safe and Effective Medicines for Neonates:
      Report of the US Food and Drug Administration First Annual Neonatal Scientific
      Workshop, October 28-29, 2014.
AB  - The First Annual Neonatal Scientific Workshop focused on the needs of the neonate
      by addressing the basic question: what information is required to inform decision
      making both at the regulatory level and at the bedside? Priority therapeutic
      areas include neonatal lung, brain, and gastrointestinal injury, retinopathy of
      prematurity, sepsis, and neonatal abstinence syndrome. Scientific progress in
      these therapeutic areas, regulatory standards, and the acceptable design and
      conduct of clinical trials must be aligned. This report will review potential
      approaches to enhancing neonatal drug development.

PMID- 30227032
TI  - Best Practice Recommendations Regarding the Assessment of Palatability and
      Swallowability in the Development of Oral Dosage Forms for Pediatric Patients.
AB  - The palatability of oral drugs influences patient adherence to prescribed
      regimens, especially for children. Various factors influence palatability,
      including smell, taste, texture, and dose volume. Evaluation of these factors
      plays an important role in pediatric drug development and is a target for
      regulatory scrutiny. The Global Alliance for Pediatric Therapeutics, a public
      private consortium under the guidance of the Institute for Pediatric Innovation,
      convened the Alliance Palatability Working Group to discuss the issues related to
      the assessment of palatability in the development of pediatric oral dosage forms.
      An extensive scientific literature search was conducted, in addition to a
      multicompany industry survey and a series of workshops with the Alliance
      Palatability Working Group. Based on the results, 3 best practice recommendations
      emerged regarding the assessment of palatability for oral dosage forms in
      pediatric drug development. These best practice recommendations offer researchers
      guidance for the preclinical and clinical assessment of palatability of oral
      dosage forms and serve to operationalize the assessment process within the
      overall drug development program.

PMID- 30227033
TI  - An Estimate of the Benefit-Cost Impact of the FDA Guidance on Data Monitoring
      Committees.
AB  - BACKGROUND: There is little information available about the impact that FDA
      guidances have on the clinical trial enterprise. OBJECTIVE: To estimate the
      impact of the FDA's Guidance for Industry, "The Establishment and Operation of
      Clinical Trial Data Monitoring Committees for Clinical Trial Sponsors." METHODS:
      An economic model was developed to measure the costs and potential savings
      associated with the change in data monitoring committee (DMC) usage since
      issuance of the DMC guidance for industry-sponsored clinical trials. To establish
      the change in use following the issuance of the DMC guideline, a literature
      search was conducted among high-impact medical journals during publication year
      2010 and compared to a similar analysis conducted during publication year 2000.
      Costs were obtained for DMCs and applicable clinical trials. The results were
      applied to an analysis of ClinicalTrials.gov completed trials during 2007 to
      2013. RESULTS: Review of 4200 manuscripts from publication year 2010 was compared
      to a similar literature search of publication year 2000. The mention of DMCs in
      industry-sponsored randomized controlled trials from high-impact journals
      increased from 24% to 47% (risk ratio = 1.9, P < .0001). This increased rate of
      DMCs is associated with an increase of 1045 DMCs for industry-sponsored phase 2
      and 3 interventional trials that were commenced and completed from 2007 to 2013
      and were listed in ClinicalTrials.gov . The increased cost due to these
      additional DMCs was approximately US$231 million, and the savings associated with
      early termination of clinical trials due to these DMCs was approximately US$428
      million. CONCLUSION: The DMC guidance has had a net positive economic impact on
      the clinical trial enterprise. However, noneconomic factors need to be evaluated.
      ClinicalTrials.gov could be further leveraged to explore further noneconomic
      benefits and costs of DMCs.

PMID- 30227034
TI  - Incentivizing Quality in the Manufacture of Pharmaceuticals: Industry Views on
      Quality Metrics and Ratings.
AB  - BACKGROUND: An increasing number of industry-wide quality breaches and
      consequential drug shortages have fueled interest in finding better ways to
      improve the manufacturing quality of pharmaceuticals. Quality metrics offer a way
      of focusing FDA inspectional resources by using risk-based paradigms and
      communicating the quality status of different companies to other stakeholders.
      This exploratory study investigated industry views related to the use of quality
      metrics and ratings to help advance these discussions. METHODS: A 23-question
      survey engaged 2 separate populations of industry professionals: a panel of
      identified US industry experts (n = 110) and a broader population (n = 328) of
      professionals working primarily in southern California. RESULTS: FDA metrics most
      valued by industry were warning letters and other observations, often
      characterized as "lagging" metrics. Respondents were generally hesitant to share
      information that would establish "leading" metrics, such as process performance
      measures that may warn of problems earlier. Ratings were recognized to
      incentivize higher quality by broadening stakeholder influence. However, concerns
      were identified related to the equity, misuse, or misunderstanding of the rating
      schemes and underlying metrics. CONCLUSIONS: Industry is an important stakeholder
      in the development of metrics. The concerns of industry must be recognized and
      addressed if policies related to metrics and ratings are to be effective in
      building an industry-wide quality culture.

PMID- 30227035
TI  - Evaluation of an Adaptive Maximizing Design Study Based on Clinical Utility
      Versus Morphine for TRV130 Proof-of-Concept and Dose-Regimen Finding in Patients
      With Postoperative Pain After Bunionectomy.
AB  - BACKGROUND: Conventional opioids provide powerful analgesia but also produce
      efficacy-limiting adverse effects, limiting their clinical utility (CU). TRV130
      is being evaluated to determine whether CU can be expanded by way of increased
      efficacy, decreased adverse effects, or some combination thereof. METHODS: This
      phase 2 study of TRV130 blends traditional objectives with novel design features
      aimed toward the specific strategic goal of optimizing the attributes of TRV130
      efficacy and tolerability compared with the conventional opioid, morphine. The
      adaptive maximizing design (AMD) was developed to maximize assignment of future
      patients to doses that demonstrate maximum balance between efficacy and
      tolerability (ie, CU) assessed via a CU function. RESULTS: Our evaluation of the
      AMD performance characteristics reveals that the AMD has a strong capacity to
      estimate the TRV130 dose-regimens with maximum CU, assign more patients to the
      TRV130 dose-regimens with maximum CU, and, conversely, assign fewer patients to
      doses away from the those with maximum or near-maximum CU. CONCLUSIONS: Based on
      this evaluation of performance characteristics of the AMD versus a traditional
      study design, the AMD was selected for this proof-of-concept and dose-regimen
      finding study of TRV130.

PMID- 30227036
TI  - Food and Drug Administration Requirements for Clinical Studies in Pediatric
      Patients.
AB  - Many drugs approved by the US Food and Drug Administration (FDA) for use in
      adults lack adequate data on safety and efficacy in pediatric patients, a
      potential source of unintended harm to pediatric patients. Through a series of
      laws, regulations, and guidance documents, the US Congress and FDA have created a
      program both to encourage and mandate clinical studies in pediatric patients to
      develop evidence-based dosing, safety, and efficacy information. A "Pediatric
      Study Plan" (PSP) is required for every new drug. FDA provides incentives for the
      voluntary conduct of clinical trials in pediatric patients, including
      opportunities for added marketing exclusivity and for obtaining a "priority
      review voucher." FDA also mandates that clinical studies for new drugs be
      conducted in each pediatric age group (newborns, infants, children, and
      adolescents), except in circumstances where a waiver or a deferral of studies can
      be justified. Sometimes this mandate can be met by extrapolation from studies in
      adults, or from patients in one pediatric age group to another, for evidence of
      efficacy. However, separate studies of safety and dosing are usually required for
      each pediatric age group. The package insert for each new drug now must address
      the use in pediatric patients. In addition, the FDA website displays all changes
      in drug labeling related to pediatric patients (excerpted from the labels for
      easy access), summaries of all pediatric studies that have led to labeling
      changes, links to FDA medical reviews of pediatric studies, summaries of all
      pediatric safety issues presented to the FDA Pediatric Advisory Committee (with
      links to the meeting materials and transcripts), and details of deferred
      pediatric studies with their timelines and progress. These measures reflect the
      increasing attention by FDA and the medical community to the importance of
      clinical studies in pediatric patients.

PMID- 30227037
TI  - Establishing Return-on-Investment Expectations for Patient-Centric Initiatives.
AB  - There has been a proliferation of patient-centric initiatives supporting drug
      development planning and execution during the past 24 to 36 months. Patient
      centricity seeks to engage patients and the health care community as drug
      development partners and represents a fundamental departure from a legacy product
      centric research and development paradigm. As the clinical research enterprise
      gains experience, it is critical that it executes patient-centric initiatives
      well, provides sufficient support, sets realistic expectations and requires
      reasonable return on investment (ROI). This article offers insights and
      suggestions for organizations looking to establish ROI expectation and evaluation
      of their patient-centric initiatives. The article is based on ideas and concepts
      that have been shared and discussed among stakeholders throughout the clinical
      research enterprise.

PMID- 30227038
TI  - Topic of Timely Interest-Decision Criteria for Negative QT Assessment Using
      Exposure Response Analysis of Data From Early-Phase Clinical Studies: Letter to
      the Editor.

PMID- 30227039
TI  - Enhancing Quality and Efficiency in Clinical Development Through a Clinical QMS
      Conceptual Framework: Concept Paper Vision and Outline.
AB  - A quality management system (QMS) is an integrated framework through which
      organizations can systematically plan and achieve their quality objectives. While
      the International Conference on Harmonisation (ICH) Q10 provides clear guidance
      for QMS in the pharmaceutical manufacturing sector, there is no harmonized
      regulatory guidance describing a framework that provides an enterprise-wide view
      of achievement of clinical quality objectives, that is capable of being
      customized to fit an organization's unique circumstances, and that accommodates
      the variability inherent in clinical development. In the absence of such
      guidance, clinical QMS varies dramatically across industry, sometimes resulting
      in over-engineered, cumbersome systems that are not adaptable or fit-for-purpose.
      This paper will describe the ongoing activities of a TransCelerate initiative
      developing a conceptual framework for a Clinical QMS designed to provide a
      consistent, streamlined, and proactive quality approach across all stages of
      clinical research.

PMID- 30227040
TI  - Implementing the Principle of the 3 Rs Through the Indian Pharmacopoeia.
AB  - Quality and safety tests are required for regulatory approval of drugs and
      pharmaceuticals in the country to guarantee minimum safety standards, and most of
      these tests include animal usage. In the case of biological medicines, these
      safety and quality tests have to be performed on a batch-to-batch basis and
      require a large number of animals. Russell and Burch's 1959 principle of the 3 Rs
      replacement, reduction, and refinement-is now being increasingly adopted
      worldwide, and various national and international pharmacopoeias have taken
      initiatives to safeguard animals. This article details the Indian Pharmacopoeia
      Commission's initiative to implement the 3 Rs through the Indian Pharmacopoeia.
      Explored are the deletion of animal tests, such as the abnormal toxicity test at
      final lot for biologicals; the replacement of in vivo methods by in vitro
      methods; the reduction in the number of animals used where deletion of the animal
      test is not possible; and the refinement of tests to cause minimal suffering to
      the animals. In Indian Pharmacopoeia 2014, pyrogen testing using rabbits has been
      replaced by the bacterial endotoxin test in the majority of biological monographs
      keeping in view international trends and, especially for vaccine monographs,
      validated in vitro tests such as the bacterial endotoxin test as an alternative
      to the pyrogen test where justified and authorized. Steps are taken for
      introducing a single-dilution assay for the potency testing of diphtheria and
      tetanus vaccine (adsorbed) with the aim of minimizing number of animals used. The
      justified and authorized use of animals in drug manufacturing, analytic
      laboratories, and research will not only help in the expedited
      development/production of drugs but also be useful in protecting and promoting
      animal health.

PMID- 30227041
TI  - A Model Data Management Plan Standard Operating Procedure: Results From the DIA
      Clinical Data Management Community, Committee on Clinical Data Management Plan.
AB  - BACKGROUND: The DIA Clinical Data Management Community created a committee to
      develop a model standard operating procedure (SOP) for writing a data management
      plan. METHODS: The goal of the committee was to develop a plan that could be used
      by industry and academic institutions. The model was based on contributed
      examples from committee members and their experiences with current practices and
      technologies. It is understood that as new clinical trial technology is
      implemented, the SOP will require modification. RESULTS: The model SOP and
      associated templates are presented as a starting point, and each company or
      institution will need to modify them to meet its individual needs. CONCLUSION:
      The model DMP SOP produced addresses most data management issues that are present
      in any phase clinical trial while providing a flexible framework.

PMID- 30227042
TI  - Identifying and Quantifying the Accuracy of Product Name Attribution of US
      Sourced Adverse Event Reports in MedWatch of Somatropins and Insulins.
AB  - BACKGROUND: As of 2014, the US FDA was considering policy options to promote
      accurate attribution of adverse events for biosimilars. In order to assess the
      identification and traceability of biologics from multiple sources, Tufts
      University's Center for the Study of Drug Development conducted a study reviewing
      the current FDA Adverse Event Reporting System (FAERS) for reports related to
      insulin and growth hormone products. METHODS: For this study, all primary suspect
      reports that were received by FAERS for human growth hormone (hGH) and human
      insulin between the fourth quarter of 2005 and the third quarter of 2013 were
      extracted and analyzed. RESULTS: The rates of "accurate" brand (ie, identifiable)
      drug names were generally high, with a higher incidence for hGH drugs than for
      insulin drugs (92% of hGH primary suspect reports vs 84% of insulin primary
      suspect reports). Lot number completion rates were generally low, with a higher
      incidence for insulin drugs than for hGH drugs (37% of insulin primary suspect
      reports vs 13% of hGH primary suspect reports). There were 13.5% of insulin
      reports that could not be linked to manufacturers, while 7.5% of hGH reports
      could not be linked to a manufacturer. CONCLUSIONS: The completion and accuracy
      rates of FAERS data on biologics observed in this study are consistent with those
      observed in earlier studies and suggest that traceability in adverse event
      reports can be improved through more consistent use of brand names or other
      product specific identifiers and through more frequent inclusion of lot numbers.

PMID- 30227043
TI  - Quantum of Effectiveness Evidence in FDA's Approval of Orphan Drugs: Update, July
      2010 to June 2014.
AB  - BACKGROUND: This study serves as a follow-up to a March 2012 analysis conducted
      by Frank Sasinowski that reviewed the quantum of effectiveness evidence that is
      required to secure FDA approval of therapies for rare diseases, or orphan drugs,
      from the 1983 enactment of the Orphan Drug Act through June 30, 2010. The current
      study was designed to determine, over the 4 years since the original study, how
      frequently FDA has required marketing applications of drugs for rare diseases to
      provide the conventional level of proof of effectiveness that is ordinarily
      expected for most drugs for prevalent diseases. METHODS: This study employed
      methods similar to the original analysis, identifying the noncancer orphan drugs
      approved as new chemical entities by relying on FDA's publicly available
      documents for drugs approved by FDA from July 1, 2010, to June 30, 2014. These
      materials were used to identify the basis for each drug's approval, and each
      approval was analyzed and classified. RESULTS: The results of this study show
      that for just over two-thirds of all noncancer orphan drugs approved between July
      1, 2010, and June 30, 2014, FDA did not require the orphan drug applications to
      provide the conventional level of proof of effectiveness that is ordinarily
      expected for drugs for prevalent diseases. This is consistent with the results of
      the 2012 analysis. CONCLUSIONS: The findings further support that FDA has
      demonstrated extraordinarily reasonable flexibility in its review of certain
      applications for orphan drugs and reinforce the need for FDA and drug companies
      to better understand and discuss the various types of flexibility.

PMID- 30227044
TI  - Patient-Centered Therapy Development for Myotonic Dystrophy: Report of the
      Myotonic Dystrophy Foundation-Sponsored Workshop.
AB  - Myotonic dystrophy (DM) is an autosomal dominant, repeat expansion, progressive
      disorder with no drug therapies. Consequently, to better define a regulatory
      pathway in anticipation of new treatment strategies under investigation, the
      Myotonic Dystrophy Foundation convened a workshop entitled "Patient-Centered
      Therapy Development for Myotonic Dystrophy" in September 2015. Participants
      included representatives from academia, industry, the patient community, the
      National Institutes of Health (NIH) and the Food and Drug Administration (FDA).
      Presenters described the symptom burden of the disease, and existing data on DM
      biomarkers, endpoints, natural history, and benefit-risk considerations. FDA
      participants helped clarify the regulatory requirements for new drug treatment
      approvals and DM-specific issues such as variability, slow progression, and low
      prevalence. Workshop attendees gained a better understanding of DM and the
      current status of existing data and tools to support therapeutic drug research
      and development.

PMID- 30227045
TI  - Center for Drug Evaluation and Research Perspective on Quality in Clinical
      Trials.
AB  - Clinical trial quality is essential to bringing effective treatments to patients
      as quickly as possible. Clinical trials that answer important questions, yield
      meaningful data, and protect trial participants can provide data that support
      both regulatory and clinical decision making. The Food and Drug Administration's
      (FDA's) Center for Drug Evaluation and Research (CDER) encourages stakeholders to
      improve clinical trial quality and efficiency. CDER believes that a systematic
      approach to clinical trial quality-one that builds in quality up front and
      focuses on the most critical aspects of study conduct-contributes to successful
      trials. Beyond FDA's regulatory requirements for clinical trial quality, CDER is
      an active participant in multiple efforts to advance clinical trial quality,
      including the addendum to ICH E6 (Good Clinical Practice) and the Clinical Trials
      Transformation Initiative project on quality-by-design for clinical trials. These
      efforts aim to move clinical drug development to a desired state that centers on
      efficient and agile clinical development programs that reliably produce high
      quality data and adhere to important ethical standards.

PMID- 30227046
TI  - Commissioner Gottlieb and the Crusade Against Opioid Abuse: Baptism by Fire.

PMID- 30227047
TI  - Compliance of Community Pharmacists and Private General Medical Practitioners
      With Malaysian Laws on Poisons and Sale of Drugs.
AB  - BACKGROUND: Compliance of community pharmacists (CPs) and private general medical
      practitioners (GPs) with Malaysian Laws on Poisons and Sale of Drugs is crucial
      in encouraging rational supply of medicine to patients that will subsequently
      lead to rational use of medicine, especially controlled medicine and psychotropic
      substances. This study aims to identify the trend of yearly compliance rate of
      both CPs and GPs with the Malaysian Laws on Poisons and Sale of Drugs, and to
      quantify the effectiveness of disciplinary actions in improving their compliance
      level. METHODS: This is a retrospective observation study from the Sarawak state
      Pharmaceutical Enforcement Division (PED) inspection reports on CPs and GPs from
      January 1, 2012, to December 31, 2014. Descriptive statistics in numbers and
      percentages are used to present the results. RESULTS: From years 2012 to 2014,
      the compliance rate of GPs increased from 34% to 51%, while the compliance rate
      of CPs remained almost constant, with a slight drop from 53% (2012) to 50%
      (2014). The most common noncompliance found among CPs is with the Poison Acts
      1952 Section 26 Condition 2: "Records for the supply of preparations containing
      Pseudoephedrine, Ephedrine and Dextromethorphan," and among GPs, it is the
      Regulation 12 of Poisons Regulation 1952: "labeling of dispensed medicines."
      Warning letter is the most effective disciplinary action for both CPs (75%
      improvement) and GPs (67.8% improvement). CONCLUSION: This study serves as a
      baseline that provides valuable insights to policy makers, researchers, and other
      stakeholders in developing better enforcement strategies.

PMID- 30227048
TI  - Breakthrough Therapy Designation: CDER Analysis of Requests 4 Years Into the
      Program.
AB  - BACKGROUND: A breakthrough therapy designation is intended to facilitate and
      expedite development and review of new drugs to address unmet medical need in the
      treatment of a serious condition. METHODS: The Center for Drug Evaluation and
      Research (CDER) at Food and Drug Administration (FDA) analyzed 364 breakthrough
      therapy designation requests received from program inception on July 9, 2012,
      through June 30, 2016. RESULTS: Of the 364 requests received during this time,
      CDER granted 133 (37%), denied 182 (50%), and the sponsor withdrew 49 (13%)
      before CDER made a decision. CONCLUSION: This analysis provides information on
      the distinguishing characteristics of the drugs seeking this designation and the
      decisional factors used by CDER to either grant or deny breakthrough therapy
      designation requests. This paper provides greater transparency into the CDER
      decision process, so the public can better understand how breakthrough therapy
      designations are determined.

PMID- 30227049
TI  - Key Elements of Pharmacoinformatics for the Degrees of Bachelor and Master of
      Pharmacy.
AB  - The Internet and rapid development of technology has led to the application of
      pharmacoinformatic technologies in improving the efficiency of the medication use
      process. By integrating pharmacoinformatics in pharmacy education, a qualified
      workforce of pharmacists well trained in the perspective of both pharmacy
      practice and informatics for safe and positive health-related outcomes can be
      produced. This survey assessed the level of importance of the suggested topics
      for pharmacoinformatics courses for pharmacy bachelor's and master's degrees by
      giving a questionnaire to pharmacy lecturers in both public and private
      universities, and to pharmacists registered with the Ministry of Health,
      Malaysia. Briefly the study of pharmacoinformatics was classified into 5 major
      areas: Drug Information Services, Information Technology & Internet, Drug
      Formulary Management, Supply Chain Management, and Health Policy. The relative
      importance of all relevant topics were evaluated and reported. It was found that
      compared with the undergraduate level, master's degree had higher expectations,
      and thus a more in-depth pharmacoinformatics curriculum content. In addition, the
      experiential method of learning instead of formal lectures alone was used on
      pharmacy master's courses. The findings from this survey could serve as a guide
      to improve pharmacoinformatics curricula in order to produce pharmacists who can
      safely and effectively utilize pharmacy informatics to disseminate information in
      drug use.

PMID- 30227050
TI  - Pre-approval Access Terminology: A Cause for Confusion and a Danger to Patients.
AB  - BACKGROUND: Patients who are seriously ill and have run out of available
      treatment options may seek access to investigational agents that have not yet
      been fully vetted by regulatory agencies for safety and efficacy and approved for
      use in human subjects. Over time, a variety of terms have evolved internationally
      to denote mechanisms for providing access to such unapproved investigational
      agents. The lack of consistency in terminology used to describe this process is
      confusing at best and, at worst, possibly even detrimental to patients. METHODS:
      To highlight variation around the globe in terminology denoting pre-approval
      access to investigational agents, we conducted extensive Internet searches to
      locate specific legislation, guidance, or policy documents describing access
      mechanisms in numerous countries. We created a table of results intended to
      convey a sampling of international terminological diversity. RESULTS: The
      profusion of terms used internationally to indicate pre-approval access to
      investigational agents is evident. We recommend a shift toward the use of "pre
      approval access" as an umbrella term encompassing all forms of access to
      unapproved agents. We also recommend use of the phrases "individual/named patient
      regulatory routes for pre-approval access" and "group/cohort regulatory routes
      for pre-approval access" to differentiate between pre-approval access programs
      designed for single patients, versus those designed for groups of patients.
      CONCLUSIONS: There is a pressing need to revisit and better align pre-approval
      access terminology at the international level. Adopting the umbrella term "pre
      approval access" may be a useful strategy for initiating and promoting
      harmonization of terms to reduce potential confusion by patients and health care
      decision makers regarding experimental treatment options.

PMID- 30227051
TI  - Using Individual Experiences With Experimental Medications to Predict Medication
      Taking Behavior Postauthorization: A DIA Study Endpoints Workstream.
AB  - From humanistic, clinical, and economic perspectives, it is important to
      understand patients' health care attitudes and behavior. Of particular interest
      in defining the value of a pharmacologic therapy is medication adherence. A DIA
      workstream was convened to define medication adherence in a drug-development
      context, explore the relevance of medication nonadherence from various
      stakeholder perspectives, examine methods of collecting medication adherence data
      in, or alongside, drug-development programs, and propose a robust approach to
      predicting medication adherence in routine clinical practice from data derived
      in, or alongside, drug-development programs. This article summarizes the
      workstream findings and guidance as it pertains to these objectives. The proposed
      approach to predicting medication adherence involves a patient-reported outcome
      (PRO) questionnaire that contains a series of standardized questions for patient
      self-completion that asks about likelihood of medication adherence in clinical
      practice, and that queries about perceived benefits and barriers to adherence on
      exit from an efficacy trial. This methodology can be used to both gain a better
      understanding of the experimental medication and compare the experimental
      treatment to comparator therapy as warranted. This approach may assist regulators
      and payers in making meaningful treatment comparisons and facilitate
      manufacturers in developing empirically based patient-support programs. This
      workstream will now turn to the challenge of developing the PRO questionnaire in
      line with this proposal.

PMID- 30227052
TI  - The Enigma of Pharmacovigilance of Patient Support Programs: A Survey of
      Marketing Authorization Holders in Europe.
AB  - BACKGROUND: Pharmacovigilance of patient support programs (PSPs) has been the
      subject of debate, legislation, and guidance, and regulatory inspections over the
      last half-a-dozen years. PSPs often involve direct contact between patients or
      caregivers and health care professionals and are sponsored by marketing
      authorization holders (MAHs). PSPs have no scientific hypothesis under study, and
      are not governed by a protocol. Adverse events and suspected adverse reactions
      are expected to arise. Management of safety data is governed by a patchwork of
      incongruous guidelines worldwide, leaving room for varying interpretations.
      METHODS: A survey of MAHs was conducted to inquire about methods, techniques and
      scope of pharmacovigilance activities concerning PSPs and similar organized data
      collection systems. The survey was conducted over a 6-week period by contacting
      pharmacovigilance operations managers in a broad range of MAHs. RESULTS: The
      survey was completed by 18 of 35 MAHs. The vast majority of MAHs (94%) conduct
      market research. Patient support programs were sponsored or supported by 89% of
      the respondents, with 67% of MAHs sponsoring or supporting disease management
      programs or social media resources. CONCLUSION: Pharmaceutical industry responses
      to the challenge of pharmacovigilance of patient support programs are varied. In
      general there has been a consistent response to the European pharmacovigilance
      regulations and the accompanying guidance introduced in June 2012. As evidenced
      by the following survey results, many companies have adopted a risk-based
      approach first assessing each PSP for probability of AE generation, and then
      setting up a contract and processes to ensure appropriate collection, collation,
      and assessment of reports of suspected adverse reactions. At the same time, the
      survey results indicate that many companies are not as mature in their oversight
      of PSPs. The authors recommend collaboration within the industry to define and
      agree to industry standard approaches for oversight of PSPs and the adoption of
      evidence-based simplification of the current regulatory guidelines concerning
      safety monitoring and reporting, as the current burden is onerous, and over a
      period of several years has not yielded any information on medically important
      new risks. Specifically, the authors recommend the formation of a CIOMS Expert
      Working Group to spearhead this industry collaboration to find a better path
      forward.

PMID- 30227053
TI  - Mobile Medical Applications for Dosage Recommendation, Drug Adverse Reaction, and
      Drug Interaction: Review and Comparison.
AB  - BACKGROUND: There is a need for a collation and comparison of the content of the
      mobile medical applications (apps) to allow health care professionals to know
      precisely which app they can rely on to gain access to appropriate drugs
      references. This study aims to evaluate the features of mobile medical apps based
      on 3 major functions: Dosage recommendation, drug adverse Reaction, And Drug
      Interaction (DoReADI). METHOD: A review and comparison of mobile apps available
      in Google's Play Store (Android system) and Apple's App Store (iOS system) were
      performed. The comparison was based on the availability of options, especially
      DoReADI functionalities. The assessment criteria were as follows: requirement for
      an Internet connection, subscription fee charged, size of app, dose
      recommendation, drug indication, dose calculator, drug picture, dose adjustment,
      pregnancy safety, interaction checker, interaction classification, clinical
      teaching advice, contraindicated drug, black box warning, adverse effect,
      contraindication or precaution, as well as toxicology and pharmacology
      information. RESULTS: Eight mobile medical apps were included and used to compare
      their features and functionalities. The 4 apps that scored the highest (14/17
      points) are: Lexicomp(r), Epocrates(r), Micromedex(r), and Drugs.com (r).
      Lexicomp and Micromedex do not provide the image of the drug and have an access
      subscription fee. Epocrates does not provide interaction classification and
      clinical teaching advice, and occupies a large space in the memory to be
      installed. Meanwhile, My Blue Book(r) scored the lowest (9/17 points) because
      certain features such as toxicology information, drug interaction, clinical
      teaching advice, contraindicated drug, and black box warning were not included.
      CONCLUSION: Based on the features assessment criteria of each mobile medical
      application, Lexicomp, Epocrates, Micromedex, and Drugs.com are the apps that
      scored the highest. Epocrates and Micromedex are useful for checking drug
      interactions. In addition, some of the apps have additional features for the
      DoReADI criteria, for example, dose calculator and interaction classification.

PMID- 30227054
TI  - Structured Benefit-Risk Assessment Across the Product Lifecycle: Practical
      Considerations.
AB  - BACKGROUND: Assessing the benefit-risk profile of a medicinal product is a
      complex but fundamental activity that sponsors and regulators must perform
      throughout the product's lifecycle. In order to improve the transparency and
      consistency of the decision-making process, regulators and sponsors alike are
      increasingly applying a structured approach to benefit-risk assessment. However,
      to our knowledge, there has been little practical guidance in the published
      literature regarding how to embed such a process organizationally. This paper
      seeks to address this gap. METHODS: Using a case study approach, we describe (1)
      how to integrate a lifecycle approach to structured benefit-risk assessment
      within a biopharmaceutical company; (2) key issues to anticipate during
      implementation, and (3) best practices and lessons learned to date. RESULTS:
      Based on our experience, key prerequisites for successful implementation included
      the selection of a structured benefit-risk assessment (SBRA) framework;
      application of a "core" approach to conducting SBRA with an accompanying
      template; development of a supporting standard operating procedure; and cross
      functional team training. Common implementation challenges encountered were (1)
      facilitating cross-functional team adoption of SBRA nomenclature and analytic
      methods, including the use of a value tree and effects table, and (2) applying
      the SBRA framework to different products with heterogeneous data sources.
      CONCLUSION: Conducting transparent, systematic benefit-risk evaluations is an
      emerging "best practice" for medicinal product lifecycle management. Our
      experience using such an approach resulted in improvements in the consistency,
      quality, conciseness and strategic value of our benefit-risk assessments, and
      increased transparency and harmonization in the communication of the product
      benefit-risk profile.

PMID- 30227055
TI  - Trans-Pacific Partnership Agreement and Its Impact on Accessibility and
      Affordability of Medicines: A Meta-synthesis.
AB  - This article aims to discuss the main consequences of the implementation of the
      Trans-Pacific Partnership Agreement (TTPA) in the pharmaceutical sector in regard
      to public health, focusing on the accessibility and affordability of medicines.
      This paper also looks at the likely impact of the TPP agreement on access to
      affordable medicines. The potential effects of provisions in the final text are
      explored based on the context of developed and developing countries. A meta
      synthesis study design was used. The thematic analysis technique was used to
      generate themes and a decision tree of the TTPA meta-synthesis. PubMed,
      EBSCOhost, Ovid, and Scopus databases from inception until the first week of
      January 2016 were used. Only peer-reviewed journals that discussed TPPA's impact
      on the pharmaceutical sector were included. Data were extracted by 2 reviewers
      and then verified by 3 senior researchers. The extracted data were imported into
      Excel spreadsheets and coded line by line. Codes were organized into descriptive
      themes. The identified themes were cross-checked against original articles to
      ensure consistency. A total of 85 full articles and reports were reviewed and,
      finally, 32 of them were used in the meta-synthesis. Two central themes to the
      TTPA emerged: intellectual property rights and transparency. Five subthemes were
      identified under intellectual property rights: patent subject matter
      (representing scope of patentability), patent term adjustment for patent office
      delays (representing patent term extension), protection of undisclosed test or
      other data (representing data exclusivity), protection of undisclosed test or
      other data (representing patent linkage), and compulsory licensing. Meanwhile,
      transparency and anti-corruption-procedural fairness, which presents restriction
      of coverage program and reimbursement, were identified as the subthemes of
      transparency. Findings indicate that the TPPA could potentially hinder the
      affordability and accessibility of medicine, which could increase risks to public
      health.

PMID- 30227056
TI  - One Patient Is Not One Condition: Delivering Patient-Centered Care to Those With
      Multiple Chronic Conditions.
AB  - While patients with multiple chronic conditions account for the bulk of health
      care spending in many countries-71 cents of every dollar spent on US Medicare
      beneficiaries-medical research and care remain organized around singular diseases
      and specialties. This siloed approach places the burden of managing multiple
      conditions on patients, who often have difficulty navigating the health care
      system and following treatment recommendations. This helps explain why patients
      with multiple chronic conditions have more unplanned admissions to the hospital,
      worse health outcomes, and poorer quality of life. Longer life expectancies,
      aging populations, and the increasing incidence of chronic conditions will vastly
      increase the number of patients living with multiple conditions, placing strains
      not only on patients but on governments and businesses paying for their care. In
      Japan, for example, the elderly will make up more than a quarter of the
      population by 2018, putting tremendous pressure on the country's health system as
      chronic diseases become more prevalent with age.  Pharmaceutical companies can
      play a pivotal role in addressing these issues by developing products, programs,
      and services geared to the unique physical, social, and emotional challenges
      patients with multiple chronic conditions face. Companies also can have a
      significant impact by promoting collaboration and communication among health
      system stakeholders, expanding the knowledge base about patients' experiences
      with multiple chronic conditions, and developing therapies and tools to help
      patients adhere to treatments and improve their quality of life.

PMID- 30227057
TI  - Patient Centricity and Pharmaceutical Companies: Is It Feasible?
AB  - Various health care bodies (regulatory, health technology assessment, academia,
      health care providers, scientific journals) request patient input in their
      decision-making processes. This represents a shift from disease-centered to
      patient-centered approaches to health care. What does this "patient centricity"
      mean for the pharmaceutical industry? A panel of senior pharmaceutical industry
      representatives discussed the following key issues: why the pharmaceutical
      industry needs to be part of the patient-centric movement; how the industry can
      become patient-centric; and what a patient-centric company actually does. We
      summarize the panel's point of view on these key questions. The industry's role
      has been to develop the science and medicines for prevention or treatment of
      disease. In response to changes in the current health care environment, the
      industry should focus its efforts on initiatives that will improve impact and
      value for patients and carers. True patient centricity requires a change in the
      industry's cultural mindset, an increase in public trust, clearer roles and
      responsibilities within pharmaceutical organizations, openness to learn from
      others, and a framework to measure success. There are examples of industry
      engagement with patients throughout the drug discovery and development process.
      Patient-reported outcomes are becoming increasingly important endpoints in
      trials; they capture information of relevance to patients, identify preferences,
      and better inform treatment decision making. Understanding the patient experience
      can improve disease management at critical points in the disease course. The
      future of patient centricity lies in coordinated efforts by and alignment of
      multiple health care stakeholders, which can only be achieved through
      collaborations and consortia, with the industry playing a key role.

PMID- 30227058
TI  - Typographic Changes in Package Leaflets of the European Union Based on the
      Example of German Versions Between 2005 and 2015.
AB  - BACKGROUND: Typography significantly influences the legibility and usability of
      patient information. This study investigated the implementation and changes of
      different typographic subjects in package leaflets used in the European Union.
      METHODS: A randomly selected sample of all German package leaflets investigated
      in 2005 was reanalyzed in 2015 for different important and predefined typographic
      subjects. RESULTS: The 138 package leaflets revisited in 2015 showed significant
      increases in word count (average 2551 words), font size (1.43 mm x-height, 2.0 mm
      cap-height), line spacing (3.13 mm), use of text attributes (for example, lists
      in 94.2% and bold print in 83.2% package leaflet's body text), use of light
      condensed or condensed font (34.1%), and use of portrait format (81.9%) ( P <=
      .015). Otherwise, line length significantly decreased to on average 62.6
      characters per line ( P = .012) and the classes of fonts used remained almost
      unchanged. CONCLUSION: To achieve any further increase of package leaflet font
      size and other typographic improvements, a significant decrease in text volume is
      essential. To this end, replacing the current 840-word QRD template with a 200
      word version would allow optimization of typography in all package leaflets,
      without deleting information essential for patients or incurring any unfavorable
      format increase.

PMID- 30227059
TI  - Clarifying the Discussion Points in New Drug Application Reviews for Approval in
      Japan by a Government Advisory Council.
AB  - BACKGROUND: In Japan, the Pharmaceutical Affairs and Food Sanitation Council
      (PAFSC) of the Ministry of Health, Labour and Welfare conducts discussions during
      the final stages of drug application reviews based on reports from the
      Pharmaceuticals and Medical Devices Agency (PMDA). Any disagreements or points of
      contention raised during these discussions can result in delays to drug approval.
      It is therefore important to characterize the points of discussion in the PAFSC
      meetings to optimize the process and enable more efficient drug approval reviews
      in Japan. METHODS: We investigated the recorded minutes of PAFSC meetings
      concerning 229 drug applications (comprising 164 new drug applications and 65
      supplemental applications) between fiscal years 2012 and 2014. The discussion
      points were characterized according to their main topics, and the frequency of
      each topic was examined. RESULTS: Clinical trials were the most frequent topic of
      discussion. Issues concerning package inserts were also prominent because many
      required reconsiderations and follow-up after council meetings. In particular,
      additional precautions and further clarification regarding drug indications and
      dosage were major points for reconsideration and follow-up. CONCLUSIONS: The
      review process may be improved if the points identified in this study are taken
      into consideration during the drug review process by the PMDA.

PMID- 30227060
TI  - The Landscape of Contract Manufacturing of Sterile Injectable Drugs: Who Is
      Making What, Where, and for Whom.
AB  - BACKGROUND: Contract manufacturing of prescription drugs is perceived to be on
      the rise, as companies look to optimize manufacturing capacity by either
      outsourcing or manufacturing for others. The lack of transparency into these
      proprietary arrangements has led to concerns that outsourcing may result in an
      overly concentrated manufacturing base, making the system more vulnerable to drug
      shortages. METHODS: Using nonpublic, internal FDA data, we link 374 sterile
      injectable new drug applications (NDAs) and 797 abbreviated new drug applications
      (ANDAs, otherwise known as generics) with finished dosage form manufacturing
      facilities in which the drugs were made as of November 2014. We then examine
      which kinds of firms were outsourcing which products and for whom. RESULTS: We
      find that NDAs were twice as likely to be outsourced as ANDAs: 39% versus 19%.
      Outsourced NDAs were just as likely to be made in the US as in Western Europe
      (45%), but outsourced ANDAs were mostly made in Asia (57%). Large application
      holders outsourced 10% of their application portfolio. They also manufactured for
      others-about 14% of applications they made were for others. Sixty-one percent of
      contract manufacturing firms were small and of those, 76% owned no applications.
      Because so much contract manufacturing of sterile injectables was being done by
      small players, there were no discernable differences in market concentration
      measures between application holders and drug manufacturers. CONCLUSION: The
      landscape of sterile injectable contract manufacturing in 2014 was diverse, with
      small and large companies participating. This diversity resulted in a market
      similar in its concentration on the ownership and manufacturing sides.

PMID- 30227061
TI  - Pharmaceutical Compounding: Our First Foray Into Common Ground and Controversies.

PMID- 30227062
TI  - Improving the Quality of Compounded Sterile Drug Products: A Historical
      Perspective.
AB  - The term compounding generally refers to the practice of combining, mixing, or
      altering ingredients of a drug product to create a medication tailored to the
      needs of an individual patient. Compounding has long been a common activity
      within the practice of pharmacy. The scope of pharmacy compounding includes the
      compounding of sterile products, a practice that is especially prevalent within
      hospitals, home infusion pharmacies, and, more recently, outsourced compounding
      facilities. Reports of patient morbidity and mortality associated with compounded
      products have led many over the years, including the US Food and Drug
      Administration (FDA), to call for more stringent federal oversight of pharmacy
      compounding to ensure patient safety. A tipping point was reached in 2012 with
      the emergence of a multistate outbreak of fungal meningitis and other infections
      in patients who received contaminated steroid injections compounded by the New
      England Compounding Center in Framingham, Massachusetts. This article describes
      the history of the practice and regulation of pharmacy compounding, culminating
      in the passage by Congress of the Compounding Quality Act of 2014.

PMID- 30227063
TI  - Challenges in the Ethical Review of Research Involving Complementary and
      Integrative Medicine.
AB  - Complementary and integrative medicine (CIM) involves using practices outside
      mainstream Western medicine, often derived from Eastern traditional medicine, and
      combining those practices with Western medicine. Conducting CIM research that is
      necessary to determine whether particular interventions are beneficial and safe
      will involve a set of ethical challenges. Institutional review boards (IRBs),
      also known as research ethics committees or research ethics boards, are
      responsible for determining that research studies involving human subjects
      appropriately address ethical and regulatory concerns inherent to the research.
      Like other research with human subjects, research involving CIM is subject to
      ethical review and ongoing oversight by an IRB. IRBs are often challenged by the
      review of CIM. These challenges include accounting for cultural differences and
      the interests of competing stakeholders. In this report, we describe these issues
      that were the focus of a workshop that was part of an international conference
      held in Seoul, Korea, on April 4, 2015.

PMID- 30227064
TI  - Trend Analysis of FDA Warning Letters Issued to Medical Products About Violations
      to Current Good Manufacturing Practices (CGMP) Between 2007 and 2014.
AB  - BACKGROUND: The US Food and Drug Administration (FDA) is responsible for
      protecting public health. Issuance of a warning letter is the FDA's principal
      means of achieving prompt voluntary compliance with regulations. The objective of
      this study is to analyze the trends of warning letters issued to medical products
      about current good manufacturing practices (CGMP) violations during 2007-2014,
      with a secondary purpose of providing suggestions to manufacturers on how to
      avoid warning letters. METHODS: Warning letters were collected from the FDA
      website, and information about the date of issuance, company, country, and type
      of medical product was collected from the letters related to medical products
      about CGMP violations. Descriptive statistics were performed for the analysis.
      RESULTS: A total of 997 warning letters were issued to medical products about
      CGMP violations during 2007-2014. It showed an upward trend in the number of
      warning letters from 2009 to 2011. In 2011, it reached a maximum and the FDA
      released 159 letters. Overall, 685 (68.7%) letters were issued to medical
      devices, 223 (22.4%) to finished pharmaceuticals, followed by active
      pharmaceutical ingredients (5.7%), biological products (including blood products)
      (1.8%), and pharmacy compounding (1.4%). Despite a sharp reduction in 2013, the
      annual number of warning letters released to medical devices was larger than
      others; conversely, changes in other products remained relatively stable.
      CONCLUSIONS: The issuance number of warning letters increased during 2009-2011.
      Medical device manufacturers received the largest numbers of letters. The
      issuance number and type of warning letters were greatly influenced by changes in
      FDA's internal enforcement procedures, drug policies and regulations, as well as
      other departments' regulations. Manufacturers should comply with regulations
      voluntarily and respond promptly to policy changes.

PMID- 30227066
TI  - Global Innovators and Thought Leaders Across the Drug Information Industry to
      Gather in Philadelphia for DIA 2016.

PMID- 30227065
TI  - Implementing Benefit-Risk Assessment for the Periodic Benefit-Risk Evaluation
      Report.
AB  - BACKGROUND: In 2012, the International Conference on Harmonisation (ICH) E2C (R1)
      guideline for periodic safety update reporting (PSUR) for medicines was revised.
      Several new concepts that expanded the scope of the report were added, including
      a new section focused on benefits and an additional section focused on integrated
      benefit-risk (B-R) assessment. These changes are reflected in the new title of
      the report, namely, the Periodic Benefit-Risk Evaluation Report (PBRER).
      Recently, structured frameworks have been developed by the pharmaceutical
      industry and regulatory agencies to facilitate B-R analysis for medicines.
      METHODS: This manuscript provides suggestions for incorporating the elements of a
      structured B-R assessment into the PBRER and also includes practical approaches
      for implementing the ICH guidelines for the B-R analysis section. RESULTS: The
      main components of a B-R assessment for the PBRER include decision context; key
      benefits and key risks; strengths, limitations, and uncertainties of the
      evidence; risk management; and the overall B-R conclusions. CONCLUSIONS: A
      structured, systematic approach to defining a medicine's B-R profile will help
      ensure compliance with this ICH objective for the PBRER.

PMID- 30227067
TI  - Regulatory Informatics Reveals Minimal Residual Disease Trends in Hematologic
      Malignancies.
AB  - BACKGROUND: The application of regulatory informatics to identify trends in
      clinical trials is a new methodology with the potential to shape drug development
      programs. As an endpoint in hematologic malignancies, minimal residual disease
      (MRD) measures the depth of response to treatment, and has been given initial
      attention in draft regulatory guidelines and workshops by health authorities in
      the EU and US. METHODS: In this paper, we analyze hematologic malignancy trials
      by searching for terms in Trialtrove, parsing the data sets with ActivePerl, and
      determining significance with the statistical package R. RESULTS: We identify
      trends in the use of MRD compared to other endpoints and in different indications
      over time from 2005 to 2014. Results show that 2 trends of endpoint and MRD use
      emerge over time and the use of MRD as a primary endpoint is growing. We also
      take a case-study approach to investigate the functional context of MRD in
      chronic lymphocytic leukemia and show that it is predominantly used to determine
      MRD-negativity and also in correlation with other endpoints. CONCLUSION: The
      application of informatics tools to regulatory science can evaluate the role and
      context of MRD as it evolves in the changing pharmaceutical landscape.

PMID- 30227068
TI  - Review Experiences and Regulatory Challenges for Pharmaceutical Development in
      Japan Using a Quality-by-Design Approach.
AB  - BACKGROUND: A significant number of inquiries are issued during the review of
      pharmaceutical products developed using the quality-by-design (QbD) approach in
      Japan. The purpose of this article was to identify key elements specific to QbD
      development that should be described in the Quality Overall Summary (QOS)
      dossier. METHODS: The review reports of the Japanese Pharmaceuticals and Medical
      Devices Agency (PMDA) were investigated to identify review points for QbD
      products. Based on the results, key considerations for preparing the QOS of QbD
      products were determined. RESULTS: The primary review points for QbD products
      were control strategy (~30%), design space (~15%), and real-time release (~15%).
      Additionally, the market authorization application form (AF) was discussed more
      frequently for QbD products than for products developed using a traditional
      approach. Based on the results, a "QOS checklist for QbD products" was developed
      to highlight key elements of QbD products that should be included in the QOS.
      CONCLUSIONS: It is important to explain the scientific rationale for the control
      strategy, design space, and real-time release in the QOS and how "regulatory
      flexibility" is expressed in the AF. The QOS checklist enables applicants to
      prepare an appropriately detailed QOS that should satisfy the PMDA's critical
      review points. The following are recommended for further discussion topics to
      enable efficient and consistent review by the PMDA for QbD products: (1) Clear
      guidance on how to express "regulatory flexibility" in the AF and (2) a "QOS
      checklist for QbD products" that is agreed upon by both regulatory agencies and
      pharmaceutical companies.

PMID- 30227069
TI  - Improving Regulatory Education: Can We Reconcile Employers' Expectations With
      Academic Offerings?
AB  - BACKGROUND: The growing belief that an effective regulatory function is vital to
      the successful development of medical products has spurred initiatives in
      regulatory education. To help prepare highly skilled professionals, some academic
      institutions have begun to incorporate new competencies into their curricula and
      to offer innovative programs in the field of regulatory studies. METHODS: This
      study is the first national survey aimed at identifying the degree of adoption of
      an educational model based on well-defined professional competencies for graduate
      programs in regulatory studies. RESULTS: Respondents disclosed the challenges
      faced by faculty in implementing such a model. The study revealed the relevancy
      of this type of model and that a competency-based approach is largely perceived
      as a prerequisite for aligning a program's mission and vision with the skills
      that graduates need in the job market. Survey results show a strong general
      agreement regarding the suitability of a competency-based education model for
      regulatory studies. CONCLUSIONS: The challenges in implementing such a model, as
      described by survey participants, are significant but can be addressed. The
      barriers to implementation of regulatory curricula based on a competency-based
      education model should be better understood so that academic programs can educate
      highly skilled regulatory professionals. Such a workforce could best contribute
      to the delivery of high-quality, safe, and effective medical products.

PMID- 30227070
TI  - Medicines Adaptive Pathways to Patients (MAPPs): A Story of International
      Collaboration Leading to Implementation.
AB  - After nearly a decade of discussion, analysis, and development, the Medicines
      Adaptive Pathways to Patients (MAPPs) initiative is beginning to see acceptance
      from regulators, industry, patients, and payers, with the first live pilot
      project initiated under the guidance of the European Medicines Agency in 2014.
      Although it is a significant achievement to see the first asset being placed into
      human trials under an adaptive pathway, there is much to be learned regarding the
      multinational and multi-stakeholder effort that has driven the growing acceptance
      of MAPPs as a methodology and concept, as well as the need for continued and
      increasing international collaboration to foster the wider adoption of MAPPs.
      Changes in available science and technology, as well as a number of challenges in
      the current system, outlined in this paper, are transforming approaches to
      medicines development and approval. It is these challenges that have led directly
      to the groundbreaking MAPPs collaboration between the Massachusetts Institute of
      Technology Center for Biomedical Innovation's New Drug Development Paradigms
      Initiative, the EMA, patient, payer and health technology assessment groups, the
      European Federation of Pharmaceutical Industries and Associations, and the
      Innovative Medicines Initiative-a European public-private partnership. This
      article examines the development of MAPPs, from inception of the concept, to the
      establishment of this trans-Atlantic initiative, and examines challenges for the
      future.

PMID- 30227071
TI  - Navigating Through a Complex and Inconsistent Regulatory Framework: Section 503B
      of the Federal Food Drug and Cosmetic Act Outsourcing Facilities Engaged in
      Clinical Investigation.
AB  - The integrity of unbiased clinical data is essential to the future of the health
      care system by facilitating the discovery of lifesaving medicines and ensuring
      investigational drugs are safe and effective. Since 2002, the US pharmaceutical
      industry has invested over $500 billion, which is the largest research and
      development investment of any sector of the US economy. As a consequence of this
      significant investment, pharmacy compounders and other stakeholders must be
      acutely aware of the consequences of noncompliance. Pharmacy compounders are
      required to navigate through a complex and ever-changing regulatory landscape
      governed by US federal and state authorities competing for oversight and
      enforcement authority. In particular, pharmacy compounders participating in
      clinical investigation are faced with inconsistent federal and state drug
      labeling regulations, which can lead to enforcement for violating acceptable
      standards for clinical investigation and informed consent. As FDA registrants,
      Outsourcing Facilities are able to produce large volumes of clinical supplies
      without the need for prescriptions for individually named patients. Some states,
      however, may have prescription drug labeling laws that could thwart the ability
      to provide these clinical supplies. Accordingly, researchers should be aware of
      the implications of federal and state laws, including any inconsistencies, prior
      to engaging in clinical investigation.

PMID- 30227072
TI  - Statistical Considerations for an Adaptive Design for a Serious Rare Disease.
AB  - BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, disabling
      autoimmune disorder of the central nervous system. Clinical trials in NMOSD
      present unique design and statistical challenges to adequately determine
      treatment effect and to minimize risk. METHODS: The N-MOmentum trial
      (NCT02200770) is evaluating the efficacy and safety of MEDI-551, an anti-CD 19 B
      cell depleting monoclonal antibody, in patients with NMOSD and employs a number
      of unique design features. Patients are randomized (3:1) to receive MEDI-551 or
      placebo for up to 197 days. NMOSD attacks are evaluated by the investigator and
      confirmed by an independent adjudication committee. The primary endpoint is time
      to first relapse as determined by adjudication committee. Sample size re
      estimation and futility analyses are planned interim analyses. Novel multiplicity
      adjustment methods are developed to control the study-wise type I error. Methods
      for assessing inter- and intrarater reliability are proposed. CONCLUSIONS: The N
      MOmentum study minimizes exposure to placebo for individual patients. The
      application of several statistical methods in the N-MOmentum trial is novel in
      NMOSD and aims to achieve a balance between minimizing risk and maintaining
      scientific integrity.

PMID- 30227073
TI  - Pharmaceutical Pricing and Reimbursement in Japan: For Faster, More Complete
      Access to New Drugs.
AB  - BACKGROUND: In Japan, National Health Insurance (NHI) has ensured that all
      Japanese citizens can use the health services they need for more than 50 years.
      This paper gives an overview of the Japanese NHI drug price listing scheme and
      practice, and it also discusses the issue of drug price setting and health
      insurance system from the viewpoint of better patient access to new drugs as well
      as the environment for innovative new drug development. METHODS: For each New
      Molecular Entity (NME) approved between October 2004 and December 2014, we
      checked its presence in the list of NHI drug prices as of January 31, 2015, to
      calculate the NHI coverage rate and the average time between marketing approval
      and the date of NHI listing. RESULTS: A total of 304 NMEs were listed in the NHI
      price list during the study period, and the NHI coverage rate (excepting
      preventive vaccines) was 97.4%. The average time between marketing authorization
      and the initiation of reimbursement was 66 days. There were 88 drugs that gained
      premiums for innovativeness/usefulness. CONCLUSIONS: From the view of NHI
      coverage scope and speed, the hurdle to access new drugs in Japan is shown to be
      lower than in other countries that also set public prices for reimbursement.
      Although the difficulty of controlling health expenditures increases, drug
      pricing that properly reflects the drug's clinical value is important in that it
      also furthers the development of medical technology. Better price setting can
      also facilitate patient access to innovative drugs.

PMID- 30227074
TI  - A Paradigm Shift Towards Patient Involvement in Medicines Development and
      Regulatory Science: Workshop Proceedings and Commentary.
AB  - The Copenhagen Centre for Regulatory Science (CORS) and Biopeople at the
      University of Copenhagen held a workshop in May 2015 titled "Patient Involvement
      in Medicines Development and Approvals: A Paradigm Shift Towards True Patient
      Impact in Medicines Development and Regulatory Science" that acknowledged the
      importance of having patients more involved in the entire process of medicines
      research and development (R&D) and life cycle management. Four key stakeholders,
      representing patients, academia, industry, and regulatory authorities, each gave
      their view and perspective on the status and challenges of current patient
      involvement. From the 3 breakout sessions, it was concluded that patient-reported
      outcomes (ie, the report of the status of a patient's health condition that comes
      directly from the patient, without interpretation of the patient's response by a
      clinician or anyone else), was considered as an important tool when deciding
      endpoints. It was agreed that professionalization of the patient within medicine
      R&D to some extent would be necessary for obtaining influence. However, the
      industry should also seek to accommodate to the patient instead of waiting
      passively for patients to become educated. A much better organized and stronger
      involvement of patients was called for. However, this should not only rely on
      goodwill, but should preferably be implemented by legal requirements, so as to
      secure compliance by all stakeholders. An independent platform with the purpose
      of providing access to patient experience was proposed. A research and
      educational center such as CORS, which was founded on cross-sectorial and cross
      disciplinary cooperation, is an example of an institution that could be a good
      starting point for hosting such a platform.

PMID- 30227075
TI  - Telaprevir-Induced Renal Adverse Events in Japanese Patients Reported in the PMDA
      Adverse Drug Reactions Reporting Database.
AB  - BACKGROUND: Telaprevir is a protease inhibitor currently used in the treatment of
      chronic hepatitis C virus (HCV) infection. One of its adverse effects is renal
      impairment. The Pharmaceutical and Medical Device Agency (PMDA) in Japan reported
      on telaprevir-related renal dysfunction in 2012. In this study, renal adverse
      events of telaprevir were investigated using the Japanese Adverse Drug Event
      Report database. Patient profiles with adverse events might provide useful
      information for HCV therapy. METHODS: We screened the case reports in Japanese
      Adverse Drug Event Report database (JADER) of the PMDA. The profiles of patients
      with renal adverse events were analyzed. RESULTS: The present results showed that
      reports of renal adverse events were most common in male patients between 60 and
      69 years of age. Significant factors that affect the clinical outcomes of renal
      adverse events were not detected. However, it was suggested that anorexia is
      associated with renal adverse events. CONCLUSIONS: The number of reports of renal
      adverse events were highest in male patients 60 to 69 years of age treated with
      telaprevir. In addition, our findings suggested that anorexia is correlated with
      renal adverse events after telaprevir treatment. Further investigation is
      required to clarify the mechanism of renal impairments during triple therapy.
      Such knowledge might improve the safety of telaprevir therapy.

PMID- 30227076
TI  - Sterile Compounding Pharmacies: States That Do and Do Not Require Compliance With
      USP <797> Versus FDA 483s.
AB  - Traditional pharmacy compounding involves the modification of a dosage form to
      fit the needs of a patient, as prescribed by the patient's physician, and serves
      a vital need within the health community. Unites States Pharmacopeia-National
      Formulary (USP-NF) General Chapter <797>, titled "Pharmaceutical Compounding
      Sterile Preparations," is the gold standard to which modern-day pharmacists
      compounding sterile products are held. In this article, the FDA 483 inspection
      reports received by sterile compounding pharmacies were divided into 2
      categories: facilities in the United States that require compliance with USP
      <797> and those that do not require compliance with USP <797>. Results revealed
      no association between the number or category of 483 comments and state
      requirements to comply with USP <797>. The impact of voluntary registration of
      compounding pharmacies with FDA in accordance with the 2013 Drug Quality and
      Security Act (DQSA) has yet to be determined. The author recommends a national
      database of all pharmacy compounding facilities that lists the types of
      manufacturing in each facility to increase transparency and target audits, as
      well as the institution of rewards for quality in the generic industry to help
      avoid drug shortages.

PMID- 30227077
TI  - An Interview With Penny Van Esterik, MA, PhD, as Interviewed by Paige Hall Smith,
      MSPH, PhD.

PMID- 30227078
TI  - A Review of Qualitative Data Analysis Practices in Health Education and Health
      Behavior Research.
AB  - Data analysis is one of the most important, yet least understood, stages of the
      qualitative research process. Through rigorous analysis, data can illuminate the
      complexity of human behavior, inform interventions, and give voice to people's
      lived experiences. While significant progress has been made in advancing the
      rigor of qualitative analysis, the process often remains nebulous. To better
      understand how our field conducts and reports qualitative analysis, we reviewed
      qualitative articles published in Health Education & Behavior between 2000 and
      2015. Two independent reviewers abstracted information in the following
      categories: data management software, coding approach, analytic approach,
      indicators of trustworthiness, and reflexivity. Of the 48 ( n = 48) articles
      identified, the majority ( n = 31) reported using qualitative software to manage
      data. Double-coding transcripts was the most common coding method ( n = 23);
      however, nearly one third of articles did not clearly describe the coding
      approach. Although the terminology used to describe the analytic process varied
      widely, we identified four overarching trajectories common to most articles ( n =
      37). Trajectories differed in their use of inductive and deductive coding
      approaches, formal coding templates, and rounds or levels of coding. Trajectories
      culminated in the iterative review of coded data to identify emergent themes. Few
      articles explicitly discussed trustworthiness or reflexivity. Member checks ( n =
      9), triangulation of methods ( n = 8), and peer debriefing ( n = 7) were the most
      common procedures. Variation in the type and depth of information provided poses
      challenges to assessing quality and enabling replication. Greater transparency
      and more intentional application of diverse analytic methods can advance the
      rigor and impact of qualitative research in our field.

PMID- 30227079
TI  - Optimized Gemcitabine Therapy in Combination with E7 Peptide Immunization Elicits
      Tumor Cure by Preventing Ag-Specific CTL Inhibition in Animals with Large
      Established Tumors.
AB  - The role of chemotherapeutic agents in tumor immunotherapy is still
      controversial. In this study, we test using a TC-1 tumor model whether
      gemcitabine plus E7 peptide vaccine regimens (E7 peptides+CpG-ODN+anti-4-1BB Abs)
      may result in tumor cure in mice with large established tumors, with a focus on
      their effects on Ag-specific cytotoxic T lymphocyte (CTL) and myeloid-derived
      suppressor cell levels. Gemcitabine inhibited tumor growth by its direct
      cytotoxicity to tumor cells in vivo. E7 peptide vaccine regimens enhanced Ag
      specific CTL lytic and antitumor therapeutic activity. Initial combination
      therapy using gemcitabine and E7 peptide vaccine regimens resulted in tumor
      regression with tumor relapse in animals with large established tumors, which
      appeared to result from the suppression of Ag-specific CTL activity by
      gemcitabine treatment. However, optimization of gemcitabine therapy by reducing
      its dose and frequency led to complete tumor regression without any recurring
      tumors in all tested mice even after discontinuation of therapy, possibly due to
      Ag-specific CTL responses. Thus, this study shows that the optimal dose and
      therapy frequency of gemcitabine are critical for achieving tumor cure in tumor
      bearing animals undergoing E7 peptide vaccine regimen therapy, mainly by
      preventing CTL suppression. These findings may have implications for designing
      peptide-based therapeutic vaccines in cancer patients undergoing chemotherapy.

PMID- 30227080
TI  - Detection of large sequence insertions by a hybrid approach that combine de novo
      assembly and resequencing of medium-coverage genome sequences.
AB  - Large sequence insertion (LSI) is one of the structural variations (SVs) that may
      cause phenotypic differences in plants. To identify the LSIs using medium
      coverage sequencing data of four wild soybean (Glycine soja) genotypes, we
      designed a hybrid approach combining de novo assembly and read mapping. Total
      reads and reads with both ends unmapped were independently assembled into
      "ordinary contigs" and "orphan contigs", respectively, and subjected to pairwise
      alignment and stringent filtering. This approach predicted 24 LSIs averaging 2682
      bp in size, with no overlap with SVs detected by Pindel, BreakDancer, or
      ScanIndel, and they were validated by PCR. Compared with the soybean (Glycine
      max) reference genome, 20 LSIs were located outside genic regions. One of the
      four LSIs within a genic region, LSI05, is located in the coding DNA sequence
      region of a protein kinase superfamily gene (Glyma.08G123500). It caused delayed
      translation initiation and loss of 24 amino acids in the wild soybean genotype
      CW12. LSI05 was more frequently observed in 29 G. soja accessions than in 34 G.
      max accessions. Identified LSIs would be genomic resources harboring novel gene
      contents for studying SVs and improving crops. Moreover, our cost-efficient
      approach may be applicable to other plant species.

PMID- 30227081
TI  - Study Design and Use of Inquiry Frameworks in Qualitative Research Published in
      Health Education & Behavior.
AB  - Qualitative methods help us understand context, explore new phenomena, identify
      new research questions, and uncover new models of change. To better understand
      how researchers in health education and health behavior use qualitative methods,
      we reviewed qualitative articles published in Health Education & Behavior from
      2000 to 2015. We identified 48 articles that met our inclusion criteria and
      extracted information on the qualitative inquiry framework, use of theory, data
      collection methods, sampling strategy, general analysis approach, and reporting
      of results. Use of common qualitative inquiry frameworks was rare, with just one
      grounded theory study, five ethnographies, and one case study. No studies were
      framed using phenomenological or narrative inquiry approaches. Theory was used
      most commonly to select sensitizing constructs for analysis (41.7%) and to inform
      development of data collection instruments (27.1%). Interviews were the most
      common data collection method (66.7%), with focus groups next most common
      (39.6%). Sampling was typically purposive (87.5%), although often not labeled as
      such. Almost all (95.8%) the articles used quotes to illustrate themes and more
      than half (58.3%) used descriptors of magnitude (e.g., most, some) to report
      findings. The use of qualitative methods by health education and behavior
      researchers could be enriched with more intentional application of a broader
      range of inquiry frameworks. More deliberate application of a range of inquiry
      frameworks has the potential to broaden the types of research questions asked,
      application and generation of theory, study design, analytic strategies, and
      reporting of results.

PMID- 30227082
TI  - The State of the Journal 2018: A Report to Our Readers.

PMID- 30227083
TI  - Finding Meaning With Creativity in the Past, Present, and Future.
AB  - Being creative is considered a desirable trait, yet most empirical studies
      emphasize how to increase creativity rather than explore its possible benefits. A
      natural connection is how creativity can enhance life's meaning. Many of the core
      concepts in work on the meaning of life, such as the needs for coherence,
      significance, and purpose or the desire for symbolic immortality, can be reached
      through creative activity. The synthesis of these two constructs-creativity and
      the meaning of life-is discussed with a temporal model encompassing past,
      present, and future pathways to creativity. The past pathway can help one
      understand and reflect on life. The present pathway can remind one of life's joy
      and the many possible connections with humanity. Finally, the future pathway
      strives to ensure some type of legacy that may resonate with younger generations.

PMID- 30227084
TI  - The Management of Melasma on Skin Types V and VI Using Light Emitting Diode
      Treatment.
AB  - OBJECTIVE: This study investigated light emitting diode (LED) treatment for
      patients with melasma on darker skin types. BACKGROUND: Melasma is a common
      disfiguring skin condition in women which is difficult to treat and is
      refractory. The cause of melasma remains unclear. METHODS: In this study, 60
      female participants aged between 25 and 60 years, who presented with melasma,
      were enrolled (n = 39.85). They were purposely assigned to two groups according
      to their skin types. Both groups received a total of 36 LED light treatments over
      a period of 9 months. RESULTS: Both subjective and objective results indicated a
      significant improvement of melasma. Statistical analyses revealed significant
      improvements in both groups. CONCLUSIONS: The results of this study suggest that
      LED is effective in managing melasma. These results will provide a basis for
      future therapeutic use of phototherapy to improve melasma.

PMID- 30227085
TI  - Antimicrobial Activity of Phenyllactic Acid Against Enterococcus faecalis and Its
      Effect on Cell Membrane.
AB  - 3-Phenyllactic acid (PLA) was reported to have an effective antimicrobial
      activity. This study evaluated the antimicrobial activity of PLA against
      foodborne Enterococcus faecalis and its effect on cell membrane. The minimum
      concentration of PLA to inactivate E. faecalis in brain heart infusion broth was
      5 mg/mL. PLA solutions of 5 and 10 mg/mL can inactivate E. faecalis population
      >=6 log CFU/mL within 60 and 30 min, respectively. The cell membranes of most E.
      faecalis cells were damaged after PLA treatment according to the images of
      scanning electron microscopy and transmission electron microscopy. The
      differences in the regions of cell membrane protein, fatty acid, and
      polysaccharide were revealed by Fourier transform infrared spectroscopy, which
      further indicated cell membrane damages. The cell membrane permeability was
      increased when the concentration of PLA treatment was increased in the membrane
      permeability assays. Finally, almost all bacterial cells were damaged after
      treatment with 10 mg/mL PLA for 30 min, further confirmed by flow cytometry
      analysis. This study concluded that PLA is effective in inactivating E. faecalis
      cells through the leakage of intracellular components caused by cell membrane
      damage.

PMID- 30227086
TI  - Genetic and Chromosomal Differentiation of Rhamdia quelen (Siluriformes,
      Heptapteridae) Revealed by Repetitive Molecular Markers and DNA Barcoding.
AB  - Rhamdia quelen, a species of Heptapteridae, is considered to be a complex because
      of taxonomic and phylogenetic inconsistencies. Determining the physical location
      of repetitive DNA sequences on the chromosomes and the DNA barcode might increase
      our understanding of these inconsistencies within different groups of fish. To
      this end, we analyzed R. quelen populations from two river basins in Brazil,
      Paraguay and Parana, using DNA barcoding and different chromosomal markers,
      including U2 snDNA, which has never been analyzed for any Rhamdia species.
      Cytochrome c oxidase I gene sequence analysis revealed a significant
      differentiation among populations from the Miranda and Quexada rivers, with
      genetic distances compatible to those found among different species in
      neotropical fishes. Our results, in general, revealed a conservative chromosomal
      evolution in R. quelen and a differential distribution of some markers, such as
      5S rDNA and U2 snDNA, in different populations. We suggest that R. quelen must
      undergo a major revision in its morphological, genetic, and cytogenetic molecular
      and taxonomic structure to elucidate possible operational taxonomic units.

PMID- 30227087
TI  - Invasive Pulmonary Aspergillosis: Risks for Acquisition and Death in a Community
      Hospital.
AB  - BACKGROUND: Recent cases of hospital-acquired (HA) aspergillosis on our Trauma
      Service raised the question of whether this represented an outbreak or just
      increased case identification. PATIENTS AND METHODS: After Institutional Review
      Board approval, we performed a retrospective analysis of all 117 patients with
      positive pulmonary Aspergillus cultures at Grand Strand Medical Center from 2010
      through 2016. The diagnosis of community-acquired (CA) invasive pulmonary
      aspergillosis (IPA) was determined when patients were admitted with a pneumonia
      and the diagnosis was made within the first week of hospitalization. RESULTS: Of
      patients with fungus cultures (3929), 3% (117) were positive for Aspergillus.
      More than 70% (84) of patients were colonized. The remaining 33 patients were
      treated for IPA. Twenty-seven patients had chronic respiratory problems and
      presented with a new lower respiratory illness; 23 had CA IPA diagnosed within
      the first week of admission with 17% mortality rate; four patients had a delayed
      diagnosis (probable CA) with a 75% mortality rate. The six remaining patients all
      underwent a surgical procedure and were suspected to have HA aspergillosis. There
      was a significantly higher rate of HA in the surgical subset in comparison with
      all nonsurgical patients (p < 0.03). Patients treated for IPA were more likely to
      be receiving high dose prednisone (>20 mg/day, p < 0.004) and their mortality
      rate was significantly higher than colonized patients (27.3% vs. 9.5%, p <
      0.026). Patients with HA IPA were divided evenly over the years of the study
      period and not thought to represent an outbreak. CONCLUSIONS: Aspergillus
      infection is an endemic infection in this region of the southern Atlantic states
      and may occur in patients with major trauma as well as patients with chronic
      pulmonary diseases. Our data support the concept that there were no breaches in
      air quality to cause the IPA. Aggressive fungal therapy should be considered in
      all at-risk patients.

PMID- 30227088
TI  - A New Method for Investigation of Different Tissues Using Femtosecond Laser Mass
      Spectrometry.
AB  - BACKGROUND: Femtosecond laser mass spectrometry (FLMS) has become an important
      tool for investigation of chemical and biological materials in many areas from
      medical to industrial. OBJECTIVE: In medicine, the morphological examination of
      tissues is determined by performing pathological investigations under microscope.
      However, some novel improvements or developments must be performed for much
      faster diagnosis of the tissue during the operation when patient is under
      anesthesia. METHODS: The information obtained from the tissue under the
      microscope remains very limited because it cannot reveal characteristics of the
      whole molecules. For this reason, some novel methods for analysis of tissues are
      important issues to be achieved. This process can be performed using FLMS much
      quicker than traditional techniques. The aim of this study is to develop a new
      procedure for interpretation of mass spectra obtained from different types of
      muscle tissues, such as lamb, bones, and beef obtained from the butcher. RESULTS:
      The results obtained in this study are believed to open a new window for these
      kinds of applications for cancer diagnosis on human tissue studies, as a faster
      analysis technique to give some concrete contributions to pathological
      examinations. Both, principal component analysis statistical approach and FLMS
      technique offer a great opportunity to identify the biological materials from
      mass spectra. In conclusion, this present study interprets a great data from
      bone, beef, and lamb, which show that we can distinguish these different types of
      materials using FLMS data and statistical approaches. CONCLUSIONS: Eventually,
      the experimental results obtained from our group studies present that these types
      of tissues can easily be distinguished using small m/q peaks in the lower region
      (m/z <=100 amu) of the mass spectra by courtesy of FLMS.

PMID- 30227090
TI  - Shear Bond Strength of Different CAD/CAM Ceramics: Acid vs Er:YAG Laser Etching.
AB  - OBJECTIVE: To evaluate whether Er:YAG laser etching could be an alternative
      surface treatment to hydrofluoric (HF) acid etching. BACKGROUND: Surface
      treatment is important to bonding properties and utility times of computer aided
      design/computer aided manufacture (CAD/CAM) dental ceramics. The traditional
      method of HF acid etching is harmful to humans if not handled properly. MATERIALS
      AND METHODS: Four different CAD/CAM ceramics (Vita Mark II, IPS Empress CAD, IPS
      e.max CAD, and Vita Enamic) were cut into 72 blocks and divided into 6 groups
      according to different surface treatments (n = 12): Group A: no treatment; Group
      B: HF acid; and Group C to F: different Er:YAG laser power settings (300, 400,
      500, and 600 mJ). Ten blocks of each group were measured for shear bond strength
      (SBS) and the failure modes were evaluated; the rest blocks were observed by
      scanning electronic microscopy (SEM). RESULTS: HF acid etching resulted in the
      highest SBS for Vita Mark II, IPS Empress CAD, and Vita Enamic; however, the
      difference was not statistically significant (p > 0.05) compared to the second
      highest group of laser with 600 mJ in IPS Empress CAD. For IPS e.max CAD, the
      highest SBS was obtained from laser group with 400 mJ. The SBS results were
      consistent with failure modes and surface characterizations in SEM images.
      CONCLUSIONS: Our results showed that Er:YAG laser had little impact on Vita Mark
      II and Vita Enamic; but proper power settings could be an alternative surface
      treatment to HF acid etching (600 mJ for IPS Empress CAD and 400 mJ for IPS e.max
      CAD).

PMID- 30227089
TI  - GPR30 Attenuates Myocardial Fibrosis in Diabetic Ovariectomized Female Rats: Role
      of iNOS Signaling.
AB  - Premenopausal women have a reduced risk for cardiovascular disease. Estrogen
      deficiency augments cardiac inflammation and oxidative stress and, thereby,
      aggravates myocardial fibrosis (MF) and diastolic dysfunction in hypertensive
      female rats. However, estrogen replacement therapy has no effect on myocardial
      infarction and cardiac fibrosis in postmenopausal women. Further clinical studies
      showed that high blood glucose levels in patients with diabetes is an important
      cause of MF, but the underlying mechanism is unclear. To experimentally address
      this issue, diabetes mellitus (DM) was induced by injecting streptozotocin and
      administering a high-fat diet in ovariectomized (OVX) rats. High degrees of
      fibrosis and apoptosis were detected in the cardiac tissue of these rats,
      together with increased expression of iNOS. Further treatment with the G protein
      coupled estrogen receptor 30 (GPR30) agonist G1 decreased iNOS expression and the
      apoptosis rate in cardiac tissue significantly and inhibited cardiac fibroblast
      (CF) proliferation. Similar trends were observed in cultured CFs treated with
      high concentrations of fat and glucose. In addition, treatment with the iNOS
      specific inhibitor W1400 attenuated iNOS and vimentin expression, which is
      associated with a marked reduction in MF. These results suggest that GPR30
      activation inhibits MF in diabetic OVX female rats by suppressing cardiac iNOS
      activity and consequently NO levels. Thus, GPR30 activation may provide novel
      cardioprotection strategies for postmenopausal women, especially those with DM.

PMID- 30227091
TI  - Percutaneous Lumbar Laser Discectomy: Literature Review and a Retrospective
      Analysis of 65 Cases.
AB  - BACKGROUND: Percutaneous lumbar laser discectomy is a minimally invasive
      treatment option for patients with a contained disc herniation with back and/or
      leg pain. OBJECTIVE: The goal of this study was to present our experience and
      results with patients who underwent percutaneous lumbar laser discectomy in our
      practice. METHODS: A total of 65 patients were included, and their charts were
      retrospectively reviewed. RESULTS: The most common level at which we performed
      the laser discectomy was the L5/S1 level 47.4% of the time. The next most common
      level was L4/L5 37.2% of the time and the least common level was L3/4 15.4% of
      the time. Neuritis was reported in four patients, which was treated with
      medication in two patients, and resolved in all four patients. The average
      preprocedure visual analog scale (VAS) score was 7.6/10 (range, 5-10/10). There
      was an improvement in the VAS score at 2-week follow-up. The average VAS score at
      2-week follow-up was 3.7/10 (range, 0-10/10). The average VAS score at 6-week
      follow-up was 4.3/10 (range, 0-8/10). The average VAS score at 3-6 months was
      4.1/10 [range, 0-8/10 and at 6-12 months was 4.2 (range, 0-8/10)]. CONCLUSIONS:
      Appropriate patient selection and following a systematic stepwise approach are
      important in treatment planning for patients in whom percutaneous laser
      discectomy is being considered. Following appropriate patient selection criteria
      maximizes the success rate of percutaneous laser discectomy. In our experience
      with patients with persistent back and/or leg pain not responding appropriately
      to conservative therapy, percutaneous laser discectomy offers a minimally
      invasive treatment option with nominal complications.

PMID- 30227092
TI  - Bonding Strength of Orthodontic Brackets on Porcelain Surfaces Etched by Er:YAG
      Laser.
AB  - OBJECTIVE: To evaluate the effect of erbium: yttrium aluminium garnet laser
      conditioning bond strength of orthodontic brackets on porcelain surfaces.
      BACKGROUND: There are few studies that evaluate the effect of Er:YAG laser about
      orthodontic bonding on porcelain surface. The efficacy of Er:YAG laser in
      porcelain conditioning is controversial. MATERIALS AND METHODS: Ninety ceramic
      specimens were randomly divided into five group, group A: etched with
      hydrofluoric (HF) acid; group B and C: etched with an energy parameter of 250 mJ,
      20 Hz and 300 mJ, 20 Hz by Er:YAG laser instrument; group D and E: etched with an
      energy parameter of 250 mJ, 20 Hz and 300 mJ, 20 Hz of Er:YAG laser with HF
      etching. Afterward, two samples selected randomly from each group were evaluated
      by scanning electron microscopy. Brackets were bonded on the remaining samples,
      which were stored in distilled water and thermocycled. Each group was measured by
      shear bond strength (SBS), tensile bond strength (TBS), porcelain fracture index
      (PFI), and adhesive remnant index (ARI) calculation. Data were statistically
      analyzed using SPSS software. RESULTS: The SBS and TBS in group E were the
      largest. Comparing SBS and TBS of HF group and other Er:YAG laser group, there
      were statistically significant difference (p < 0.05). PFI was significantly
      higher in shear force group than the tensile force group. HF group had higher ARI
      score than the other groups. CONCLUSIONS: Porcelain surfaces etched by 250 mJ, 20
      Hz of Er:YAG laser combined with HF acid can get enough bond strength and have
      lower porcelain fracture rate for orthodontic bracket bonding.

PMID- 30227094
TI  - Editorial Board Member's Commentary: Commissioner Scott Gottlieb's Predictable
      Imaginarium.

PMID- 30227093
TI  - Comparison of 0.025% FK-506, 0.05% Cyclosporin A, and 0.3% Sodium Hyaluronate Eye
      Drops for the Treatment of Botulinum Toxin B-Induced Mouse Dry Eye.
AB  - PURPOSE: To compare the effects of FK-506, cyclosporin A (CsA), and sodium
      hyaluronate (HA) eye drops for the treatment of botulinum toxin B (BTX-B)-induced
      mouse dry eye. METHODS: CBA/J mice were randomized into 5 groups. The groups
      received treatment with eye drops containing 0.025% FK-506 combined with 0.3% HA
      (FK-506+HA group), 0.025% FK-506 (FK-506 group), 0.05% CsA (CsA group), 0.3% HA
      (HA group), or 0.9% saline (saline group) 3 days after an intralacrimal gland
      injection with 20 mU of BTX-B. Tear production, corneal fluorescein staining,
      blink rate, and the mRNA and protein expression levels of inflammatory cytokines
      were measured. RESULTS: FK-506+HA eye drops increased tear production and reduced
      the corneal fluorescein staining scores at all time points after treatment
      compared with those in the saline group. Compared with those in the saline group,
      the tear production and severity of corneal epithelial defects in the FK-506
      group were significantly improved at weeks 2 and 4. Compared with the saline eye
      drops, the CsA eye drops ameliorated only tear production and corneal fluorescein
      staining scores at week 4 after administration. The FK-506+HA, FK-506, and CsA
      eye drops downregulated the expression of inflammatory cytokines in both the
      keratoconjunctival tissues and lacrimal glands at week 4. CONCLUSIONS: The
      topical application of 0.025% FK-506 combined with 0.3% HA, 0.025% FK-506, or
      0.05% CsA can suppress the expression of inflammatory cytokines and can alleviate
      the signs of dry eye. Topical application of 0.025% FK-506 combined with 0.3% HA
      showed the best therapeutic effect and may be a possible therapy for dry eye.

PMID- 30227095
TI  - Update From the Field of Renal Sympathetic Denervation: A Focus on Safety
      Nomenclature Considerations.

PMID- 30227096
TI  - Implications of CRISPR-Based Germline Engineering for Cancer Survivors.
AB  - Cancer survivors can carry germline mutations that will be transmitted to their
      progeny. Today, many of these mutations have been identified and can be tracked.
      With the recent development of genome-editing technologies and CRISPR (clustered
      regularly interspaced short palindromic repeats), the possibility of genetically
      modifying the human germline-gametes and embryos-has never been closer. This
      perspective has sparked a controversy within the scientific community with
      reactions ranging from calls for a ban on germline modification to cautious
      approval of further research. This Editorial analyzes the possible adoption of
      CRISPR-based germline engineering to prevent the spread of cancer predispositions
      in the human population. We discuss whether the genomic edition of human sperm
      and eggs would contribute to rectifying or altering the heritable genome. We
      anticipate the emergence of a new form of liberal eugenics fueled by a logic of
      offer and demand from stakeholders such as cancer survivors and their relatives
      and offspring, but also from fertility clinics, biotech firms, insurers, and
      clinicians. From a regulatory perspective, validating the clinical safety and
      utility of CRISPR-based germline engineering is an essential step. However, with
      time, gradually perfecting the technology and assessing the economic benefits for
      stakeholders could soften society's resistance and align opinions in support of
      genomic decontamination of human germlines. This progressive shift would be
      justified in the name of cancer prevention as well as a moral obligation to
      facilitate the conception of cancer-free children at a cost that is acceptable to
      individuals and health systems.

PMID- 30227097
TI  - Bone Mineral Density to Assess Pediatric Bone Health in Drug Development.
AB  - BACKGROUND: Pediatric bone health is an important part of the safety assessment
      of inhaled corticosteroids and certain other drugs. Current regulatory guidance
      for assessment of bone health for intranasal and inhaled corticosteroid drugs is
      a single 1-year study of linear growth. OBJECTIVE: The objective of this study
      was to assess whether a significant change in bone mineral density (BMD) could be
      observed during a 12-month period in pediatric patients being treated for asthma
      with an inhaled corticosteroid using a previously conducted study. METHODS: The
      publicly available information from the Childhood Asthma Management Program
      (CAMP) study was used to assess whether a statistically significant difference in
      BMD could be detected over a 1-year period. Patients who were at Tanner stage >=2
      were excluded from analysis as is stated in the present FDA Guidance on growth
      studies with inhaled corticosteroids, and children with any use of oral
      corticosteroids were also excluded. A comparison in BMD change over time (bone
      mineral accretion [BMA]) between baseline and 12 months of follow-up was made for
      the placebo and inhaled budesonide groups using multiple regression analysis to
      account for age, race, and gender as covariates. RESULTS: From the original 1041
      patients in the CAMP study, 74 patients met the criteria for evaluation, with 42
      patients receiving budesonide and 32 placebo patients. Children randomized to
      budesonide had a lower mean BMA than those receiving placebo (0.021 +/- 0.023
      [SD] g/cm2/y vs 0.036 +/- 0.025 [SD] g/cm2/y). CONCLUSION: In a select pediatric
      patient population, a significant change in BMA can be observed over 12 months on
      an inhaled corticosteroid. Based on this post hoc analysis, measurement of BMA as
      an assessment of pediatric bone health may be considered for certain drugs,
      especially when there is a potential signal of bone toxicity from animal or human
      data. The clinical relevance of this finding is presently unknown, and more data
      on the relationship between changes in BMA and clinical pediatric bone health
      outcomes are needed.

PMID- 30227098
TI  - The Common Pharmaceutical Market of the Eurasian Economic Union: A Regulatory
      Review.
AB  - According to the Treaty on the Eurasian Economic Union, a common pharmaceutical
      market was supposed to become operational on January 1, 2016. Nevertheless, the
      responsible parties did not meet the deadline. Although a majority of the draft
      guidelines regulating this process were already known in 2014 and 2015, the
      anticipated process itself caused anxiety among representatives of the foreign
      pharma industry, who tried to prepare for coming challenges. Among other possible
      issues, the ambiguity of transitional periods and a lack of approved legislation
      were noted. Now only a few months remain until the end of 2016, but the market is
      still not functional. Furthermore, key documents relevant to the market still
      require approval by the Eurasian Economic Commission, and some of them even
      require discussion by representatives of member states. The present review
      provides readers with basic knowledge about regulatory procedures within the EAEU
      and the document approval process. It analyzes essential legislative acts and
      consequences for the pharma industry to take into account, including marketing
      authorization pathways, specific dossier requirements, and dates of their
      implementation. At the same time, reasons for the delay in the market's opening
      and future perspectives are discussed.

PMID- 30227100
TI  - Use of Qualitative Data to Support Content Validity of Performance-Based
      Cognitive Outcome Assessments.

PMID- 30227099
TI  - An Innovative, Collaborative, and Strategic Approach to Proactively Evaluate and
      Update Drug Interactions Based on Prescribing Information of Newly Approved
      Medicinal Products.
AB  - BACKGROUND: Drug-drug interaction (DDIs) are evaluated using pharmacokinetic (PK)
      simulation models, clinical studies, and scientific publications throughout drug
      development. DDIs with Norvir (ritonavir) and combination products (eg, Kaletra
      [lopinavir/ritonavir]) containing ritonavir as a PK enhancer are relevant,
      because these drugs could affect exposures of CYP3A4 substrates. Application of
      algorithms proactively identified recently approved drugs, which potentially
      cause adverse outcomes when given with drugs containing ritonavir. METHODS: An
      evidence-based medicine technology platform was used to identify newly approved
      products. PK-related information from the products' prescribing information was
      reviewed to identify DDIs with ritonavir. Algorithms were used to further
      evaluate PK, clinical, and postmarketing information pertinent to the interaction
      to determine if prescribing information required revision. RESULTS: From January
      1, 2014, through December 31, 2015, 39 newly approved drugs were identified as
      having potential interactions with Norvir and/or Kaletra. Ten drugs were
      excluded, 19 drugs went through initial screening, and 10 drugs underwent in
      depth algorithm-based analyses for DDIs. No changes to prescribing information
      for Norvir or Kaletra were recommended from evaluation of the DDIs. Regulatory
      concurrence with AbbVie decisions was 93.1% (27/29, 93.1%); in 6.9% (2/29, 6.9%)
      of the evaluated interactions, at least 1 local regulatory authority disagreed
      with recommendations, requiring label changes to incorporate the DDI information.
      CONCLUSIONS: This proactive algorithmic approach identifies and complements
      existing methods used to detect DDIs with newly approved products. Additionally,
      this approach facilitates timely communication of risks to patients and
      healthcare providers via label revisions, publications, or other regulatory
      communications.

PMID- 30227101
TI  - Dose Finding in Late-Phase Drug Development.
AB  - A drug may fail or raise concerns that must be addressed in later-phase trials
      because of an unacceptable toxicity profile, even if the drug meets expectations
      for efficacy. The problem could be due to the late onset of unacceptable
      toxicities that were not observed in early-phase trials. We explore methodologies
      to find appropriate doses in situations where a drug meets the primary efficacy
      objective but concerns about toxicity remain. In this manuscript, we propose a
      general framework to design a good phase IV trial that is designed to optimize
      the treatment regimen. In the first step, we learn from the existing data about
      the dose-response and dose-toxicity relationships and further to explore and
      establish the relationship using a statistical model. Noting the limitations of
      the exploratory analyses, these analyses are not sufficient to allow us to make
      definitive conclusions. However, the prediction obtained from the model, either
      estimated efficacy metrics or safety parameters for some doses, can be
      incorporated in the design of the phase IV trial. In the second step, we further
      propose and compare design options, including options that could effectively
      incorporate information from these exploratory analyses, for clinical trials to
      find optimal doses, including trials to fulfill postmarketing commitments or
      requirements.

PMID- 30227102
TI  - Optimized Medical Product Regulation in Mexico: A Win-Win for Public and Economic
      Health.
AB  - BACKGROUND: Medicines regulators, while performing a vital public health
      activity, are often perceived as both negative cost centers for governments and
      as impediments to innovation and economic development. The Mexican government
      recently undertook a regulatory optimization program focused on transforming the
      Mexican medicines regulatory pathway into one that is efficient, value-added,
      aligned with international norms, resource accountable, and one that protects and
      promotes public health, while also facilitating economic development. METHODS: To
      facilitate the implementation of a new national access to medicines policy, the
      national government and the Mexican medicines regulatory agency instituted a
      multifaceted series of regulatory and legal reforms, which are described in this
      paper. These reforms encompassed multiple aspects of the regulatory oversight of
      medicines: administrative processes, clinical trials oversight, reliance on
      market authorization information and reports (ie, "work products") of other
      trusted regulators, and validation of activities by both Pan American Health
      Organization (PAHO) and WHO. FINDINGS: These reforms have resulted in a marked
      positive impact on the availability of safe, effective, quality medicines at
      lower costs for Mexicans, both in the private and public sectors, while
      simultaneously facilitating expansion of the Mexican pharmaceutical industry.
      INTERPRETATION: The regulatory optimization approach undertaken by Mexico could
      be a useful model for other countries that are trying to provide appropriate
      public health protection to their citizens, facilitate access to needed quality
      medicines, and encourage local economic development.

PMID- 30227103
TI  - Adaptive Seamless Design for Establishing Pharmacokinetic and Efficacy
      Equivalence in Developing Biosimilars.
AB  - BACKGROUND: Recently, numerous pharmaceutical sponsors have expressed a great
      deal of interest in the development of biosimilars, which requires clinical
      trials to demonstrate that the pharmacokinetic (PK) and clinical efficacy are
      equivalent. Pharmacodynamics (PD) may be used in evaluating efficacy if there are
      relevant PD markers available. However, in their absence, it is necessary to
      design the associated clinical trials to include efficacy measures as the primary
      endpoint. METHODS: In this study, we propose a novel adaptive seamless PK and
      efficacy design with an efficient framework to remedy the risk of
      misspecification of efficacy parameters and to discontinue the trial evaluating
      the efficacy for futility based on the PK evaluation. Here, we consider the
      clinical development of biosimilars including their evaluation in patients rather
      than healthy volunteers under a situation where both PK and efficacy parameters
      are required to demonstrate equivalence. The original idea of the proposed method
      was to organize a clinical trial that includes the statistical analysis of PK as
      an interim analysis, with sample size recalculation of the efficacy data.
      RESULTS: Our simulation study indicated that the proposed design would allow
      trials to be more efficient than with the classical design. CONCLUSIONS: This
      proposal provides appealing advantages, such as a shorter time period, additional
      cost savings, and a smaller number of patients required.

PMID- 30227104
TI  - Assessing Recall and Recognition for Important Safety Information in Digital
      Promotion for Pharmaceutical Products: Implications for Website Design.
AB  - BACKGROUND: To date, there has been little research with digital direct-to
      consumer (DTC) communication regarding pharmaceutical products (eg, product
      websites), so this study was designed to measure perception and recall of
      Important Safety Information (ISI) in websites viewed on desktops and smartphone
      devices. METHODS: A quantitative survey was conducted with 1600 self-identified
      asthma patients. Participants viewed 1 of 4 mocked-up websites for a fictitious
      asthma product in either a desktop or smartphone format that varied in the way in
      which risk information was presented and accessed. The "websites" were embedded
      in survey software that enabled behavior to be tracked and facilitated
      presentation of questions designed to assess memory and user experience. RESULTS:
      Statistically significant differences in likelihood of interacting with, and
      memory of, the ISI were observed across the 4 different presentation formats-2
      typical of existing website formats and 2 representing alternative formats-for
      both desktop and smartphone media. The traditional formats consistently
      outperformed the alternative formats overall, but when analyses are restricted to
      the subset of participants who view ISI, elements of one of the alternative
      formats proved to be superior. CONCLUSIONS: Digital presentation of different
      formats of risk information has a significant effect on recall and recognition of
      ISI associated with pharmaceutical products, and the interactive nature of
      digital material adds a layer of complexity to assessing the performance of the
      various formats.

PMID- 30227105
TI  - Reference Limits for Outlier Analyses in Randomized Clinical Trials.
AB  - BACKGROUND: Reference limits used in clinical medicine to screen and manage
      patients are typically developed nonparametrically using reference values from a
      limited number of healthy subjects using a 95th percentile reference interval. We
      have evaluated alternative methods of computation and the resulting limits for
      use in the analyses of treatment-emergent outliers in clinical trials. METHODS:
      We developed a set of alternative reference limits for 38 laboratory analytes
      based on alternative statistical methods and assessed their relative performance
      in clinical trial analysis. Performance assessment was based on the clinical
      credibility of the limits, inferential statistical performance, consideration of
      incidences for the test drug and control (placebo) in cases where the drug was
      reasonably believed to be associated with a change in an analyte (positive
      cases), and in cases where prior analyses failed to demonstrate a change
      associated with the drug (negative cases). RESULTS: Based on consideration of
      these cases, no single method resulted in optimal limits for all cases
      considered. However, with the limits developed using clinical trial subjects'
      values at baseline as reference values, excluding outliers, the robust method and
      the 98th percentile interval appeared to produce optimal limits across the
      greatest number of cases considered. CONCLUSION: Although no single method of
      limit computation will result in optimal limits for all outlier analyses for all
      analytes across all clinical trials, the 98th percentile reference interval
      robust limits based on clinical trial reference values appeared superior to
      multiple alternatives considered for such analyses.

PMID- 30227106
TI  - Clinical Importance of Antibiotic Regimen in Transrectal Ultrasound-Guided
      Prostate Biopsy: A Single Center Analysis of Nine Thousand Four Hundred Eighty
      Seven Cases.
AB  - BACKGROUND: To evaluate the effectiveness of an antibiotic regimen for prostate
      biopsy by analyzing patients who were hospitalized because of complications after
      transrectal ultrasound-guided prostate biopsy. METHODS: We reviewed
      retrospectively the medical records of 10,339 patients who underwent transrectal
      ultrasound-guided prostate biopsy at our institution from May 2003 to April 2017.
      We excluded patients with low quality data. All patients underwent urine culture
      before transrectal ultrasound-guided prostate biopsy and received intravenous
      antibiotic agents 30-60 minutes before biopsy. Patients were either given
      prophylactic quinolone or cephalosporin (second or third generation).
      Clinicopathologic factors including patient age, antibiotic regimen, number of
      biopsy cores, body mass index, prostate specific antigen, prostate volume, and
      infection-related complications that required hospitalization were subsequently
      analyzed. RESULTS: A total of 9,487 patients were included in the final analysis,
      of whom 33 patients (0.35%) were hospitalized because of infection-related
      complications. Infection-related hospitalization rates were lower in patients who
      received cephalosporin (0.2%) than in patients who received quinolone (1.59%). At
      our institution, cephalosporin has been used predominantly to prevent post-biopsy
      infections since February 2013. Only five patients (0.12%) developed infection
      related complications of the 3,863 patient who underwent transrectal ultrasound
      guided prostate biopsy since February 2013. Multivariable analysis revealed that
      use of second- or third-generation cephalosporin was the only independent
      predictor of infection-related complications. CONCLUSION: Implementing an
      effective antibiotic prophylaxis regimen at our institution by using second- or
      third-generation cephalosporin could reduce infection-related complications after
      transrectal ultrasound-guided prostate biopsy.

PMID- 30227107
TI  - Shear Bond Strength of Orthodontic Brackets Luted with RMGIC After Er:YAG Laser
      Etching with Two Pulse Modes Using a Digitally Controlled "X-Runner" Handpiece.
AB  - OBJECTIVE: To compare the shear bond strength (SBS) values of orthodontic
      brackets luted using a resin-modified glass ionomer cement (RMGIC) on enamel
      surfaces etched using either an Er:YAG laser in two different working modes, or a
      conventional etching protocol, including phosphoric acid. MATERIALS AND METHODS:
      Sixty healthy human premolars were randomly allocated to three experimental
      groups (n = 20) and etched with: Group 1: Er:YAG laser in super-short pulse (SSP)
      mode (100 mJ, 20 Hz, 2 W); Group 2: Er:YAG laser in quantum square pulse mode
      (120 mJ, 10 Hz, 1.2 W) using a digitally controlled handpiece ("X-Runner"); Group
      3 (control): 5.25% sodium hypochlorite pretreatment, then 37% phosphoric acid for
      15 sec. Stainless steel brackets were bonded using light-curing RMGIC for
      orthodontic bonding. After term cycling (1800 cycles), SBS testing was performed
      using a universal testing machine. After debonding, both enamel and bracket
      surfaces were examined to determine the amount of RMGIC still present on the
      surfaces. RESULTS: Group 3 surfaces gave the lowest mean SBS (10.6104 +/- 2.66196
      MPa), whereas Group 1 provided the highest 1 (13.1795 +/- 3.37904 MPa), which was
      significantly different from the control (Group 3, p = 0.0226). Group 2 provided
      intermediate values (11.8486 +/- 0.59832 MPa) nonsignificantly different from the
      control or from SSP (p = 0.4215 and p = 0.3082, respectively). CONCLUSIONS:
      Er:YAG laser treatment in SSP mode of enamel surfaces for orthodontic bonding
      provided higher SBS and a shear behavior of the luting material similar to the
      conventional acid-etching procedures, making it a viable alternative to acid
      etching.

PMID- 30227109
TI  - Surveillance for Early-Stage Hepatocellular Carcinoma by Ultrasound Plus Alpha
      Fetoprotein Measurement: More Details, More Significance.

PMID- 30227110
TI  - A conserved cation binding site in the DNA binding domain of forkhead box
      transcription factors regulates DNA binding by FOXP2.
AB  - FOXP2 is a transcriptional repressor involved in development of the human brain
      and is the first gene product to be linked to the evolution of human speech.
      FOXP2 belongs to the FOX superfamily of proteins that share a common winged helix
      DNA binding domain - the forkhead domain. A divalent cation (Mg2+ or Ca2+) has
      been identified bound to a group of highly conserved residues in a number of FOX
      forkhead domain crystal structures. This work aims to investigate the role of the
      conserved divalent cation binding site by studying both the structure and DNA
      binding function of the FOXP2 forkhead domain when in the presence and absence of
      either cation (Mg2+or Ca2+). The presence of the cations does not significantly
      alter the structure of the apo-FOXP2 forkhead domain. However, when in the
      presence of a cognate oligonucleotide sequence, differences are observed upon
      addition of divalent cation. These differences occur both in the structure and in
      the thermodynamic DNA binding signature of the FOXP2 forkhead domain. The
      incorporation of molecular dynamics simulations together with the experimental
      data provides us with sufficient insight so as to propose a possible role for
      divalent cations in the regulation of DNA binding to FOX transcription factors.

PMID- 30227108
TI  - Bezlotoxumab for Clostridium difficile Infection Complicating Inflammatory Bowel
      Disease.

PMID- 30227111
TI  - Long non-coding RNA BRE-AS1 represses non-small cell lung cancer cell growth and
      survival via up-regulating NR4A3.
AB  - Recently, several long non-coding RNAs (lncRNAs) have been revealed to play
      crucial roles in tumorigenesis and progression of many cancers. Nevertheless,
      more than 50,000 lncRNAs were identified in human cells and the roles of majority
      of these lncRNAs in non-small cell lung cancer (NSCLC) are unknown. In this
      study, using public NSCLC microarray data we identified a novel lncRNA BRE
      antisense RNA 1 (BRE-AS1). BRE-AS1 is significantly down-regulated in NSCLC
      tissues and cell lines. Gain-of-function and loss-of-function assays showed that
      BRE-AS1 reduces NSCLC cell viability, represses NSCLC cell proliferation, and
      induces NSCLC cell apoptosis in vitro, and represses NSCLC tumor growth in vivo.
      Mechanistic investigation revealed that BRE-AS1 physically binds STAT3, reduces
      the binding of STAT3 to the promoter of NR4A3, relieves the repression of NR4A3
      caused by STAT3, and up-regulates NR4A3 expression. Consistently, NR4A3 is
      significantly down-regulated in NSCLC tissues and the expression of NR4A3 is
      positively correlated with the expression of BRE-AS1 in NSCLC tissues. In
      addition, depletion of NR4A3 attenuates the tumor suppressive roles of BRE-AS1 in
      NSCLC. Collectively, our data demonstrate that BRE-AS1 represses NSCLC cell
      growth and survival via up-regulating NR4A3 and suggest that enhancing BRE-AS1
      may be potential therapeutic strategy for NSCLC.

PMID- 30227112
TI  - News and views about carotenoids: Red-hot and true.

PMID- 30227113
TI  - Association study on IL-4, IL-4Ralpha and IL-13 genetic polymorphisms in Swedish
      patients with colorectal cancer.
AB  - BACKGROUND: Interleukin 4 (IL-4) and interleukin 13 (IL-13) are anti-inflammatory
      and immunomodulatory cytokines which share a common cellular receptor IL4Ralpha
      and are involved in the same signaling pathways. Our purpose was to assess
      whether genetic variants within IL-4, IL-13 and IL-4Ralpha are associated with
      the risk or clinical outcome of colorectal cancer (CRC). METHODS: Three single
      nucleotide polymorphisms (SNPs) were screened in 466 patients with CRC and 445
      healthy controls. The selected SNPs were IL-4 SNP rs2243250, IL-4Ralpha SNP
      rs1801275 and IL-13 SNP rs1800925. RESULTS: We found that the genotype variant
      T/T in IL-13 gene was associated with a higher risk of CRC. Kaplan-Meier analysis
      showed that the cancer specific survival differed between C/C and CT + TT for IL
      4 SNP. Moreover, the carriers of the T allele were associated with the highest
      risk of CRC death with a hazard ratio (HR) of 1.57, 95% CI 1.06-2.36, p = .024.
      The observed effect of the T allele was restricted to stage III patients.
      CONCLUSION: Our results indicate IL-13 SNP rs1800925 as a risk factor for CRC and
      that IL-4 SNP rs2243250 could be a useful prognostic marker in the follow-up and
      clinical management of patients with CRC especially in stage III disease.

PMID- 30227114
TI  - Evaluation of sex-specific cut-off values of high-sensitivity cardiac troponin I
      and T assays in an emergency department setting - Results from the Linz Troponin
      (LITROP) study.
AB  - BACKGROUND: The aim of the present analysis was to evaluate sex-specific cut-off
      values of a high-sensitivity cardiac troponin T (hs-cTnT) assay and a high
      sensitivity cardiac troponin I (hs-cTnI) assay in an emergency department
      setting. METHODS: We retrospectively studied 1945 male and 1643 female emergency
      department patients in whom we had measured both Roche hs-cTnT and Abbott hs-cTnI
      routinely upon every troponin measurement request. We performed reclassification
      analyses of sex-specific thresholds versus sex-neutral thresholds of both assays.
      In addition, we performed sensitivity analyses to find those sex-specific cut-off
      values for the Roche hs-cTnT and the Abbott hs-cTnI assays with the lowest
      possible rate of discordant classifications by both assays. RESULTS: Compared
      with the classification by the sex-neutral thresholds (i.e., 14 ng/L for hs-cTnT
      and 26 ng/L for hs-cTnI), using sex-specific thresholds (i.e., 16 ng/L in males
      and 9 ng/L in females for hs-cTnT; and in 34 ng/L males and 16 ng/L in females
      for hs-cTnI) resulted in a total reclassification rate of 4% for hs-cTnT and 3%
      for hs-cTnI in male individuals, and of 11% and 6%, respectively, in female
      individuals. In our cohort, the sex-specific hs-cTnT cut-off values currently in
      use (i.e., 16 ng/L in males and 9 ng/L in females) were best matched to a hs-cTnI
      cut-off value of 11 ng/L in male and 5 ng/L in female individuals. Conversely,
      the sex-specific hs-cTnI cut-off values currently in use (i.e., 34 ng/L in males
      and 16 ng/L in females) were best matched to a hs-cTnT cut-off value of 49 ng/L
      in male and 24 ng/L in female individuals. These "harmonised" cut-off values
      reduced discordant classifications between both assays by 43-68% compared to
      using cut-off values currently in use. CONCLUSION: Especially in women,
      reclassification rates were high, when using sex specific versus sex-neutral
      thresholds. Best matching cut-off values for hs-cTnT and hs-cTnI were markedly
      different to those currently in use. These "harmonised" cut-off values minimised
      discordant classifications between both assays.

PMID- 30227115
TI  - BLM can regulate cataract progression by influencing cell vitality and apoptosis.
AB  - Age-related cataract (ARC) is the most common cause of severe visual impairment
      and blindness. The precise mechanisms of ARC are not completely understood, but
      it is well accepted that oxidative damage plays an important role in the disease
      pathogenesis. BLM, the key enzyme of the double-strand break repair (DSBR)
      pathway, is part of a family of DNA unwinding enzymes and has a crucial role in
      multiple steps of the DNA recombination, replication and repair processes. We
      have recently shown that BLM-rs1063147 is initially associated with nuclear ARC
      in a cross-section study. Therefore, we wanted to study the effects of BLM on ARC
      progression. In ARC patients, BLM transcription in lens capsules was decreased,
      so did the BLM protein, and after UVB irradiation, BLM mRNA and protein levels
      were increased in SRA01/04 cells. Upon silencing BLM in SRA01/04 cells and rat
      lens, cell vitality and apoptosis were altered, and the rat lens opacification
      was considerable. In conclusion, BLM can regulate cataract progression by
      influencing cell vitality and apoptosis.

PMID- 30227116
TI  - Hybrid models of genetic networks: Mathematical challenges and biological
      relevance.
AB  - We review results concerning dynamics in a class of hybrid ordinary differential
      equations which incorporates logical control to yield piecewise linear equations.
      These equations relate qualitative features of the structure of networks to
      qualitative properties of the dynamics. Because of their simple structure, they
      have been studied using techniques from discrete mathematics and nonlinear
      dynamics. Initially developed as a qualitataive description of gene regulatory
      networks, many generalizations of the basic approach have been developed. In
      particular, we show how this qualitative approach may be adapted to switching
      biochemical systems without degradation, illustrated by an example of a motif in
      which two branches of a pathway may be regulated differently when the thresholds
      for the two pathways are separated.

PMID- 30227117
TI  - Modeling of post-stroke stimulation of cortical tissue.
AB  - Following a stroke, cortical networks in the penumbra area become fragmented and
      partly deactivated. We develop a model to study the propagation of waves of
      electric potential in the cortical tissue with integro-differential equations
      arising in neural field models. The wave speed is characterized by the tissue
      excitability and connectivity determined through parameters of the model. Post
      stroke tissue damage in the penumbra area creates a hypoconnectivity and
      decreases the speed of wave propagation. It is proposed that external stimulation
      could restore the wave speed in the penumbra area under certain conditions of the
      parameters. Model guided cortical stimulation could be used to improve the
      functioning of cortical networks.

PMID- 30227118
TI  - MicroRNA-23a-5p promotes atherosclerotic plaque progression and vulnerability by
      repressing ATP-binding cassette transporter A1/G1 in macrophages.
AB  - Disruption of carotid vulnerable atherosclerotic plaque is responsible for acute
      ischemic stroke (AIS) and the early detection and intervention approach are
      greatly limited. Undertaking a microarray of microRNAs (miRNAs) in the plasma of
      AIS patients with carotid vulnerable plaques, miR-23a-5p was markedly elevated
      and was positively correlated with the plaque progression and vulnerability.
      Correspondingly, we found that miR-23a-5p expression was significantly increased
      in both plasma and macrophages from atherosclerosis mice. Bioinformatics analysis
      and in vitro knockdown experiments identified that ATP-binding cassette
      transporter A1/G1 as a novel target of miR-23a-5p. Luciferase reporter assays
      showed that miR-23a-5p repressed the 3' untranslated regions (UTR) activity of
      ABCA1/G1. Moreover, functional analyses demonstrated that transfection of miR-23a
      5p inhibitor enhanced cholesterol efflux and decreased foam cell formation
      through upregulating ABCA1/G1 expression levels. Furthermore, long term in vivo
      systemically delivered miR-23a-5p antagomir significantly increased ABCA1/G1
      expression in the aorta of ApoE-/- mice. Importantly, the miR-23a-5p antagomir
      therapy significantly reduced atherosclerosis progression and promoted plaque
      stability. Our observations indicate that miR-23a-5p promotes macrophage-derived
      foam cell formation and might be a key regulator contributing to atherosclerotic
      plaque progression and vulnerability.

PMID- 30227120
TI  - Metabolic profiling associated with autophagy of human placenta-derived
      mesenchymal stem cells by chemical isotope labeling LC-MS.
AB  - Autophagy has been reported to have a pivotal role in maintaining stemness,
      regulating immunomodulation and enhancing the survival of mesenchymal stem cells
      (MSCs). However, the effect of autophagy on MSC metabolism is largely unknown.
      Here, we report a workflow for examining the impact of autophagy on human
      placenta-derived MSC (hPMSC) metabolome profiling with chemical isotope labeling
      (CIL) LC-MS. Rapamycin or 3-methyladenine was successfully used to induce or
      inhibit autophagy, respectively. Then, 12C- and 13C-dansylation labeling LC-MS
      were used to profile the amine/phenol submetabolome. A total of 935 peak pairs
      were detected and 50 metabolites were positively identified using the dansylation
      metabolite standards library, and 669 metabolites were putatively identified
      based on an accurate mass match in metabolome databases. 12C/13C-p
      dimethylaminophenacyl bromide labeling LC-MS was used to analyze the carboxylic
      acid submetabolome; 4736 peak pairs were detected, among which 33 metabolites
      were positively identified in the dimethylaminophenacyl metabolite standards
      library, and 3007 metabolites were putatively identified. PCA/OPLS-DA analysis
      combined with volcano plots and Venn diagrams was used to determine the
      significant metabolites. Metabolites pathway analysis demonstrated that hPMSCs
      appeared to generate more ornithine with the arginine and proline metabolism
      pathway and utilized more pantothenic acid to synthesize acetyl-CoA in the beta
      alanine metabolism pathway when autophagy was activated. Meanwhile, acetyl-CoA
      conversion to fatty acids led to accumulation in the fatty acid biosynthesis
      pathway. In contrast, when autophagy was suppressed, a reduction in metabolites
      demonstrated weakened metabolic activity in these metabolic pathways. Our
      research provides a more comprehensive understanding of hPMSC metabolism
      associated with autophagy.

PMID- 30227119
TI  - The roles of telocytes in lung development and angiogenesis: An
      immunohistochemical, ultrastructural, scanning electron microscopy and
      morphometrical study.
AB  - Many studies have been carried out to investigate the occurrence and distribution
      of telocytes (TCs) in many organs. However, their morphological development is
      still unclear. This study was performed to demonstrate the morphological
      development of TCs in rabbits' lung from fetal to postnatal life using light-,
      electron- microscopy, immunohistochemistry, morphometrical and statistical
      analysis. During the fetal life, these cells formed an extensive network of
      telopodes (Tps) which were in close contact with developing alveoli, bronchioles,
      stem cells and many other interstitial components. In addition, the TCs' number
      was significantly increased around the neocapillaries in fetal lung. In the fetal
      life, TCs were stellate in shape and characterized by large cell bodies and many
      short Tps that contained abundant rER, mitochondria, and ribosomes. By gradual
      increasing of ages, TCs were spindle in shape with two Tps contained a massive
      amount of secretory structures (exosomes, ectosomes, and multivesicular bodies).
      Moreover, TCs in postnatal lung showed a significant decrease in number and
      diameter of their cell bodies and a significant increase in the length of Tps
      compared with those in fetal life. The TCs contributed with pneumocytes and
      endothelium in the formation of air-blood barrier. The TCs' immunohistochemical
      profiles for CD34, vimentin, c-kit, connexin 43, vascular endothelial growth
      factor (VEGF), and neuron- specific enolase (NSE) differed between ages during
      the lung development. This study provided an evidence that TCs contributed to
      angiogenesis, the formation of the air-blood barrier, lung organization, and
      development.

PMID- 30227121
TI  - Pill, patch or ring? A mixed methods analysis of provider counseling about
      combined hormonal contraception.
AB  - OBJECTIVE: In this study we aimed to investigate the content and process of
      contraceptive counseling surrounding combined hormonal contraceptive (CHC)
      methods (combined oral contraceptives, the ring, and the patch). STUDY DESIGN: We
      performed a mixed methods analysis of data collected as part of the Patient
      Provider Communication about Contraception study, in which reproductive age women
      and their providers were recruited at several San Francisco Bay Area clinics from
      2009-2012. Participants completed pre- and post-visit surveys, and had their
      visits audio recorded and transcribed. We performed descriptive and bivariate
      analyses of the entire cohort to examine associations between demographic
      characteristics and pre-existing method preferences with method selection and
      counseling content, and coded transcripts of a subset of the sample for salient
      themes related to content and process of counseling about combined hormonal
      contraceptive methods using a directed content analysis approach. RESULTS: The
      overall sample included 342 women, with 152 women (44%) having a preference for a
      specific CHC prior to their visit, 127 women (37%) had a preference for a non-CHC
      method, and 63 (18%) having no existing method preference. Of the women who
      reported preferring a CHC in their pre-visit survey, the majority (72%) chose
      that method. We found that women were inconsistently counseled about the range of
      CHC methods. For example, women who had no pre-visit method preference (52%) or
      who preferred the ring (54%) or the patch (73%) were more likely to receive
      comprehensive counseling about the three CHC methods than were women who
      preferred combined oral contraceptives (35%) or non-CHC methods (33%). Providers
      mentioned the patch the least often, and in qualitative analysis indicated
      discomfort with prescribing this method. Side effects and benefits of methods, as
      well as strategies to enhance successful use of the chosen method, were
      inconsistently discussed. In only 73% of visits in which a woman chose a CHC did
      the provider assess the patient's ability to use the chosen method correctly, and
      in 66% of all visits in which women chose a CHC method, providers discussed what
      to do if she was dissatisfied with the method. CONCLUSIONS: Counseling about
      combined hormonal contraceptive methods often does not include information about
      all available methods, or comprehensive information about side effects, benefits,
      or logistics of use. As this counseling can impact patient's satisfaction with
      and continuation of their chosen method of contraception, future work should
      focus on designing interventions to improve providers' ability to meet patients'
      needs. IMPLICATIONS: Short acting hormonal contraception is widely used, but
      counseling for these methods often neglects key features. Comprehensive
      counseling about all methods and their individual features can improve
      contraceptive selection and use.

PMID- 30227122
TI  - Donor Willingness to Accept for Selling a Kidney for Transplantation: Evidence
      from Iran1.

PMID- 30227123
TI  - Outcome of Surgically Treated Fractures of the Condylar Process by an Endoscopic
      Assisted Transoral Approach.
AB  - PURPOSE: Fractures of the condylar process are frequent. Ideal management of
      these fractures, as discussed in the literature, is controversial. Some recent
      meta-analyses have favored open reduction and internal fixation using various
      approaches. A strictly transoral approach has been described to minimize scarring
      and risk of facial nerve injury but has restricted visibility. This retrospective
      study analyzed outcomes of patients with unilateral mandibular condyle fractures
      who were treated by open reduction and internal fixation through an endoscopic
      assisted transoral approach. MATERIALS AND METHODS: This study included 40
      patients who were operated on from January 2015 through December 2016. All
      patients underwent surgery for a condylar process fracture using an endoscopic
      assisted transoral approach. Fracture classification, demographic, and outcome
      data were collected. RESULTS: Most condylar process fractures were caused by
      falls from a height less than 3 m. Most were condylar base fractures and
      classified according to Spiessl and Schroll as Classes I and II. Sixteen patients
      showed a preoperative malocclusion, whereas 2 patients showed a slight
      postoperative malocclusion. In cases in which only 1 plate could be placed, the
      proximal fragment was shorter. A higher Spiessl and Schroll class showed a
      tendency toward longer operation times. For postoperative outcomes, 1 case of
      temporary facial palsy was the worst complication (2.5%), 2 cases exhibited
      minimal occlusal interference (5%), and 1 case exhibited a deviated mouth opening
      (2.5%). Ramus height was restored in all cases. No chronic pain was found in any
      cases. CONCLUSIONS: It is feasible to treat condylar process fractures in a safe
      manner using a transoral approach with endoscopic assistance and angled
      instruments without facial scarring and at a low complication rate. The endoscope
      improves the restricted visibility of the transoral approach, although a learning
      curve is necessary. This applies especially to dislocated fractures or to
      fractures with a short proximal fragment.

PMID- 30227124
TI  - Is Ultrasound a Useful Adjunct in the Management of Oral Squamous Cell Carcinoma?
AB  - PURPOSE: In patients with oral squamous cell carcinoma (OSCC), depth of tumor
      invasion (DOI) is correlated with prognosis. Tumor thickness (TT) is often used
      as a surrogate measurement of DOI. The aim of this study was to estimate TT in a
      sample of patients with OSCC using ultrasound sonography (USS), magnetic
      resonance imaging (MRI), and clinical assessment and compare these estimates with
      TT of the final surgical specimen. MATERIALS AND METHODS: The authors designed
      and implemented a prospective cohort study and enrolled patients presenting for
      management of OSCC. Eligible subjects had biopsy-proved OSCC and received
      clinical assessment, staging by MRI, and USS. The predictor variable was
      measurement technique by clinical assessment, USS, or MRI. The primary outcome
      variable was the maximal TT (centimeters) obtained from the final histopathologic
      specimen. Appropriate uni- and bivariate statistics were computed. RESULTS: The
      sample included 10 patients (mean age, 62.7 +/- 13.6 yr; 70% men). Two of the 10
      tumors (20%) were not adequately visualized with USS. Three of the 10 tumors
      (30%) were not seen with MRI because of dental artifact. These 3 patients' tumors
      were visualized by USS. One of the 10 tumors (10%) could not be palpated
      clinically. Three of the 10 patients (30%) did not go to surgery and were treated
      with chemoradiation because of the high tumor stage or the patient's health
      status. USS, MRI, and clinical TT measurements were underestimates compared with
      the specimen TT measurement (-0.6, -0.5, and -0.3 cm, respectively; P = .9).
      CONCLUSIONS: All 3 measurement modalities (clinical examination, MRI, and USS)
      underestimated OSCC TT compared with the final surgical specimen. There were no
      statistical differences in mean measurement or absolute value mean differences
      among measurement modalities. Notably, USS visualized the OSCC in the 3 patients
      (30%) whose tumors were poorly visualized or not visualized with MRI.

PMID- 30227125
TI  - Relevance of Intraoperative Pleural Lavage Cytology and Histologic Subtype in
      Lung Adenocarcinoma.
AB  - BACKGROUND: The association between pleural lavage cytology (PLC) and histologic
      subtype remains unknown. In this study, we evaluated the effect of a
      micropapillary pattern (MPP) in lung adenocarcinomas on results of PLC. METHODS:
      We retrospectively reviewed 600 consecutive patients with surgically resected
      pulmonary adenocarcinomas and investigated the relationship between PLC status
      and clinicopathologic factors, including a histologically identified MPP
      component. RESULTS: PLC was positive in 25 patients (4.2%). Positive PLC was
      significantly associated with MPP (p = 0.0001), lymph node metastasis (p = 0.01),
      and pleural invasion (p < 0.0001) according to multivariate analysis.
      Furthermore, the presence of MPP reinforced the effect of some established
      predictive factors, such as large tumor size, lymph node metastasis, pleural
      invasion, and lymphovascular invasion, on positive PLC. Two factors-MPP and
      positive PLC-were associated with a higher incidence of occult N2 lymph node
      metastases. The prognosis of adenocarcinomas in patients with MPP or positive PLC
      was significantly worse than that of patients without these features.
      Furthermore, the survival of MPP and positive PLC group (MPP+ PLC+) was
      significantly worse than that of MPP and negative PLC group (MPP+ PLC-, p =
      0.03). CONCLUSIONS: The presence of MPP in lung adenocarcinoma can be an
      independent predictor of positive PLC. These two factors have complementary and
      synergistic roles as prognostic factors. Detailed preoperative or intraoperative
      examination of histologic subtype and PLC findings may provide important
      information for prediction of tumor progression and decisions regarding the
      surgical procedure.

PMID- 30227126
TI  - Rare and Anomalous Origin of Left Circumflex Artery from Left Anterior Descending
      Artery.

PMID- 30227127
TI  - Development of a Congenital Heart Surgery Composite Quality Metric: Part 1
      Conceptual Framework.
AB  - BACKGROUND: Current pediatric and congenital heart surgery quality measures focus
      on operative mortality, and numerous stakeholders are interested in more
      comprehensive measures. This report describes the background, rationale, and
      conceptual framework related to the development of the first composite quality
      metric in the field. METHODS: A multidisciplinary panel reviewed methodology and
      framework related to quality measurement and several composite quality measures
      across adult cardiac surgery and other fields. The panel subsequently developed
      methodology and selected measures for a congenital heart surgery composite
      measure and reviewed potential advantages and limitations. Individual measures
      considered for potential inclusion in the composite were reviewed within the
      context of Donabedian's triad and the Institute of Medicine quality domains.
      Decisions were made through group consensus. RESULTS: The final composite measure
      selected is comprised of two domains: (1) a mortality domain (operative
      mortality) and (2) a morbidity domain (the 6 major complications endorsed by The
      Society of Thoracic Surgeons and Congenital Heart Surgeons Society plus cardiac
      arrest, and postoperative length of stay). Potential advantages include the more
      comprehensive view of quality compared with mortality alone and improvements in
      discrimination of hospital performance through increasing the number of end
      points. Potential limitations include the lack of longer term outcomes and
      challenges related to case-mix adjustment. CONCLUSIONS: We have applied and
      adapted conceptual framework and methodology related to composite quality
      measures across other fields to congenital heart surgery. The composite quality
      metric created is inclusive of both morbidity and mortality, and expands our view
      of quality in this patient population.

PMID- 30227128
TI  - Development of a Congenital Heart Surgery Composite Quality Metric: Part 2 -
      Analytic Methods.
AB  - BACKGROUND: We describe the statistical methods and results related to
      development of the first congenital heart surgery composite quality measure.
      METHODS: The composite measure was developed using the Society of Thoracic
      Surgeons (STS) Congenital Heart Surgery Database (2012-2015), Bayesian
      hierarchical modeling, and the current STS risk model for case-mix adjustment. It
      is comprised of a mortality domain (operative mortality), and morbidity domain
      [major complications, and post-operative length of stay (LOS)]. We evaluated
      several potential weighting schemes and properties of the final composite measure
      including reliability (signal-to-noise ratio) and hospital classification in
      various performance categories. RESULTS: Overall, 100 hospitals (78,425
      operations) were included. Each adjusted metric included in the composite varied
      across hospitals: operative mortality (median 3.1%, 10th-90th percentile 2.1%
      4.4%) major complications (median 11.7%, 10th-90th percentile 6.4%-17.4%), and
      LOS (median 7.0d, 10th-90th percentile 5.9d-8.2d). In the final composite
      weighting scheme selected, mortality had the greatest influence, followed by
      major complications, and LOS (correlation with overall composite score of 0.87,
      0.69, 0.47, respectively). Reliability of the composite measure was 0.73 compared
      to 0.59 for mortality alone. The distribution of hospitals across composite
      measure performance categories (defined by whether the 95% credible interval
      overlapped the STS average) was: 75% (same-as-expected), 9% (worse-than
      expected), and 16% (better-than-expected). CONCLUSIONS: This congenital heart
      surgery composite measure incorporates aspects of both morbidity and mortality,
      has clinical face-validity, and greater ability to discriminate hospital
      performance compared to mortality alone. Ongoing efforts will support the use of
      the composite measure in benchmarking and quality improvement activities.

PMID- 30227129
TI  - Multimodality Therapy for N2 Non-Small Cell Lung Cancer: An Evolving Paradigm.
AB  - BACKGROUND: Induction chemoradiation for resectable N2 non-small cell lung cancer
      (NSCLC) is used with the intent to optimize locoregional control, whereas
      induction chemotherapy given in systemic doses is meant to optimally target
      potential distant disease. However, the optimal preoperative treatment regimen is
      still unknown and practice patterns continue to vary widely. We compared
      multiinstitutional oncologic outcomes for N2 NSCLC from 4 experienced lung cancer
      treatment centers. METHODS: This collaborative retrospective study unites 4 major
      thoracic oncology centers. Patients with N2 NSCLC undergoing surgical resection
      after induction chemotherapy (CxT) or concurrent chemoradiation (CxRT) were
      included. Primary outcomes were overall and disease-free survival (OS and DFS).
      RESULTS: 822 patients were identified (CxT = 662 and CxRT = 160). There were no
      differences in 5-year OS (CxT 39.9% versus CxRT 42.9%, p = 0.250) nor in DFS (CxT
      28.7% versus 29.8%, p = 0.207). Recurrence rates (CxT 46.8% versus CxRT 51.6%, p
      = 0.282) and recurrence patterns were not significantly different (Local: CxT
      9.8% versus CxRT 9.7%; and Distant: CxT 30.4% versus CxRT 33.1%, p = 0.764).
      There was no difference in perioperative mortality. In the analyses of patients
      who underwent pretreatment invasive mediastinal staging (n = 555), there were
      still no significant differences in OS (p = 0.341) and DFS (p = 0.455) between
      the 2 treatment strategies. CONCLUSIONS: Both treatment strategies produce
      equivalent and better than expected outcomes compared with historical controls
      for N2 NSCLC, with no differences in recurrence patterns. How these conventional
      therapeutic strategies will compare with those involving immunotherapy combined
      with surgical locoregional disease control for N2 disease remains to be
      determined.

PMID- 30227130
TI  - Tricuspid Septal Leaflet Detachment for Postinfarction Septal Rupture Repair.

PMID- 30227131
TI  - Botryosphaeran reduces obesity, hepatic steatosis, dyslipidaemia, insulin
      resistance and glucose intolerance in diet-induced obese rats.
AB  - AIMS: Obesity is associated with comorbidities such as diabetes and hepatic
      steatosis. beta-Glucans have been described as effective in treating conditions
      including dyslipidaemia and diabetes. Thus, the objective of this study was to
      evaluate the effects of botryosphaeran [(1 -> 3)(1 -> 6)-beta-D-glucan] on
      obesity and its comorbidities, and understand its mechanism of action. MAIN
      METHODS: Obesity was induced in adult male Wistar rats by ingestion of a high-fat
      diet and water with sucrose (300 g/L) for 8 weeks. Control rats received standard
      diet. After six weeks, treatment commenced with botryosphaeran (12 mg/kg.b.w.,
      via gavage, 15 days), respective controls received water. Rats were divided into
      3 groups: control (C), obese (O), and obese + botryosphaeran (OB). In the 8th
      week, obesity was characterized. Feed-intake, glucose and lipid profiles, glucose
      tolerance, and concentrations of glycogen and lipids in liver were analyzed.
      Protein expression was determined by Western blotting. KEY FINDINGS: Obese rats
      showed significant increases in weight gain and adipose tissue, presented glucose
      intolerance, dyslipidaemia, and hepatic steatosis. Botryosphaeran significantly
      reduced feed intake, weight gain, periepididymal and mesenteric fat, and improved
      glucose tolerance. Botryosphaeran also reduced triglyceride and VLDL, and
      increased HDL levels. Furthermore, botryosphaeran increased glycogen and reduced
      total lipids, triglycerides and cholesterol in liver, and increased AMP-activated
      protein kinase(AMPK) activity and Forkhead transcription factor 3a(FOXO3a)
      protein expression in adipose tissue. SIGNIFICANCE: This study demonstrated that
      botryosphaeran was effective in reducing obesity, hepatic steatosis,
      dyslipidaemia insulin resistance and glucose intolerance in diet-induced obese
      rats, and these effects were, at least in part, associated with reduced feed
      intake, and AMPK and FOXO3a activities.

PMID- 30227133
TI  - Understanding lamin proteins and their roles in aging and cardiovascular
      diseases.
AB  - The occurrence of cardiovascular diseases increases with age independent of other
      risk factors, and the percentage of senescent cells is significantly elevated in
      vascular cells at atherosclerotic sites. Patients with accelerated aging
      syndromes caused by mutant lamin A protein, a structural component in nuclear
      lamina, also share many similarities with normal aged people, including the
      propensity to develop atherosclerosis. Recent studies have revealed the
      accumulation of prelamin A in normal aged vascular cells, and that lamin A
      participated as a mechanosensitive molecule in regulating various cellular
      events. These findings suggest that the ectopic expression of mutant lamin A or
      lamin A precursor (prelamin A) not only causes defects in cell mechanics, but it
      also disturbs stress-induced mechanotransduction pathways involving lamin A, both
      of which may contribute to vascular dysregulation. This review summarizes the
      current understanding of how lamin proteins are involved in vascular cell during
      aging, with a particular focus on the effect of mechanical stresses from blood
      flow on nuclear lamina of endothelial cells. Related studies are clarifying the
      role of lamin A in the progression of atherosclerosis, which will aid in the
      development of potential therapies for those suffering from lamin A-associated
      accelerated aging syndromes.

PMID- 30227132
TI  - Intranasally administered pitavastatin ameliorates pentylenetetrazol-induced
      neuroinflammation, oxidative stress and cognitive dysfunction.
AB  - AIM: The present study aimed to evaluate the neuroprotective potential of
      intranasally administered pitavastatin in the PTZ-induced kindling model.
      MATERIALS AND METHODS: Subconvulsant dose of PTZ (35 mg/kg, i.p) was administered
      on an alternate day until the development of kindling. Behavioural test,
      biochemical tests and inflammatory cytokines were estimated. Comparative
      molecular docking study of sodium valproate (VPA) and pitavastatin was performed
      to predict the binding affinity with GABAA and GABA transaminase. Intranasally
      administered pitavastatin (0.5 mg/kg and 1 mg/kg) and VPA (200 mg/kg) were used
      to investigate its protective effect. KEY FINDINGS: Comparative in-silico study
      showed docking score of -4.56 and -2.86 against GABAA receptor whereas -5.56 and 
      1.86, against GABA transaminase. Root mean square deviation (RMSD) of 0.39A and
      0.55A was found for pitavastatin and VPA, respectively. The present study showed
      the dose-dependent protective effect of intranasally administered pitavastatin
      and oral VPA against PTZ-induced seizure, cognitive impairment, oxidative stress,
      and neuroinflammation. SIGNIFICANCE: Our findings suggest that the intranasally
      administered pitavastatin is potential therapeutic approach to managing PTZ
      induced kindling and associated comorbid conditions via its antioxidant, anti
      inflammatory, and anticonvulsant potential. Further, pitavastatin can modulate
      GABAA receptor and GABA transaminase enzyme to ameliorate seizure. Meanwhile,
      more extensive studies are required to establish the molecular mechanism
      underlying the neuroprotective effect of pitavastatin.

PMID- 30227134
TI  - Serine Integrase attP Binding and Specificity.
AB  - Serine integrases catalyze the site-specific insertion of viral DNA into a host's
      genome. The minimal requirements and irreversible nature of this integration
      reaction have led to the use of serine integrases in applications ranging from
      bacterial memory storage devices to gene therapy. Our understanding of how the
      integrase proteins recognize the viral (attP) and host (attB) attachment sites is
      limited, with structural data available for only a Listeria integrase C-terminal
      domain (CTD) bound to an attP half-site. Here we report quantitative binding and
      saturation mutagenesis analyses for the Listeria innocua prophage attP site and a
      new 2.8-A crystal structure of the CTD*attP half site. We find that Int binds
      with high affinity to attP (6.9 nM), but the Int CTD binds to attP half-sites
      with only 7- to 10-fold lower affinity, supporting the idea that free energy is
      expended to open an Int dimer for attP binding. Despite the 50-bp Int-attP
      interaction surface, only 20 residues are sensitive to mutagenesis, and of these,
      only 6 require a specific residue for efficient Int binding and integration
      activity. One of the integrase DNA-binding domains, the recombinase domain,
      appears to be primarily non-specific. Several substitutions result in an improved
      attP site, indicating that higher-efficiency attachment sites can be obtained
      through site engineering. These findings advance our understanding of serine
      integrase function and provide important data for efforts towards engineering
      this family of enzymes for a variety of biotechnology applications.

PMID- 30227135
TI  - Multiple Parameters Drive the Efficiency of CRISPR/Cas9-Induced Gene
      Modifications in Yarrowia lipolytica.
AB  - Yarrowia lipolytica is an oleaginous yeast of growing industrial interest for
      biotechnological applications. In the last few years, genome edition has become
      an easier and more accessible prospect with the world wild spread development of
      CRISPR/Cas9 technology. In this study, we focused our attention on the production
      of the two key elements of the CRISPR-Cas9 ribonucleic acid protein complex in
      this non-conventional yeast. The efficiency of NHEJ-induced knockout was measured
      by time-course monitoring using multiple parameters flow cytometry, as well as
      phenotypic and genotypic observations, and linked to nuclease production levels
      showing that its strong overexpression is unnecessary. Thus, the limiting factor
      for the generation of a functional ribonucleic acid protein complex clearly
      resides in guide expression, which was probed by testing different linker lengths
      between the transfer RNA promoter and the sgRNA. The results highlight a clear
      deleterious effect of mismatching bases at the 5' end of the target sequence. For
      the first time in yeast, an investigation of its maturation from the primary
      transcript was undertaken by sequencing multiple sgRNAs extracted from the host.
      These data provide insights into of the yeast small RNA processing, from
      synthesis to maturation, and suggests a pathway for their degradation in Y.
      lipolytica. Subsequently, a whole-genome sequencing of a modified strain detected
      no abnormal modification due to off-target effects, confirming CRISPR/Cas9 as a
      safe strategy for editing Y. lipolytica genome. Finally, the optimized system was
      used to promote in vivo directed mutagenesis via homology-directed repair with a
      ssDNA oligonucleotide.

PMID- 30227136
TI  - Multiscale Molecular Visualization.
AB  - We provide a high-level survey of multiscale molecular visualization techniques,
      with a focus on application-domain questions, challenges, and tasks. We provide a
      general introduction to molecular visualization basics and describe a number of
      domain-specific tasks that drive this work. These tasks, in turn, serve as the
      general structure of the following survey. First, we discuss methods that support
      the visual analysis of molecular dynamics simulations. We discuss, in particular,
      visual abstraction and temporal aggregation. In the second part, we survey
      multiscale approaches that support the design, analysis, and manipulation of DNA
      nanostructures and related concepts for abstraction, scale transition, scale
      dependent modeling, and navigation of the resulting abstraction spaces. In the
      third part of the survey, we showcase approaches that support interactive
      exploration within large structural biology assemblies up to the size of
      bacterial cells. We describe fundamental rendering techniques as well as
      approaches for element instantiation, visibility management, visual guidance,
      camera control, and support of depth perception. We close the survey with a brief
      listing of important tools that implement many of the discussed approaches and a
      conclusion that provides some research challenges in the field.

PMID- 30227137
TI  - Volumetric Multispectral Optoacoustic Tomography for 3-Dimensional Reconstruction
      of Skin Tumors: A Further Evaluation with Histopathologic Correlation.

PMID- 30227138
TI  - Th1 and Th17 immune responses act complementarily to optimally control
      superficial dermatophytosis.
AB  - Dermatophytoses are among the most common fungal infections worldwide but little
      is known about the immune response in them. By comparing Trichophyton benhamiae
      acute superficial dermatophytosis in WT and Rag2-/- mice, we showed that TCR
      mediated immunity is critical for fungal clearance and clinical recovery. In WT
      mice, CD4+ T-cells isolated from the skin-draining lymph nodes exhibit both Th1
      and Th17 differentiation during infection, with regard to produced cytokines or
      mRNA levels of transcription factors. Using IL-17A- and IFN-gamma-deficient mice,
      we showed that IL-17A and IFN-gamma are individually dispensable, but together
      contribute to the optimal resolution of dermatophytosis. Furthermore, we
      generated and infected IL-17A and IFN-gamma double-deficient mice and showed that
      both fungal clearance and clinical recovery were much lower in these mice than in
      single-deficient mice, suggestive of the complementary roles of the two cytokines
      in dermatophytosis resolution. Thus, our data suggest that TCR-mediated immunity
      is critical for the optimal control of superficial dermatophytosis and that
      adaptive immunity is polarized to both Th1 and Th17 responses, with the Th17
      antifungal response acting on dermatophyte clearance and the Th1 one being
      involved in both fungal clearance and Th17-inflammation down-modulation.

PMID- 30227139
TI  - Both Sphingosine Kinase 1 and 2 Coordinately Regulate Cathelicidin Antimicrobial
      Peptide Production during Keratinocyte Differentiation.

PMID- 30227140
TI  - Spironolactone Depletes the XPB Protein and Inhibits DNA Damage Responses in UVB
      Irradiated Human Skin.
AB  - UVB wavelengths of light induce the formation of photoproducts in genomic DNA
      that are potentially mutagenic and detrimental to epidermal cell function. The
      mineralocorticoid and androgen receptor antagonist spironolactone (SP) was
      recently identified as an inhibitor of UV photoproduct removal in human cancer
      cells in vitro via its ability to promote the rapid proteolytic degradation of
      the DNA repair protein XPB. Using normal human keratinocytes in vitro and skin
      explants ex vivo, we found that SP rapidly depleted XPB protein in both systems
      and abrogated two major responses to UVB-induced DNA damage, including the
      removal of UV photoproducts from genomic DNA and the activation of ATR/ATM DNA
      damage kinase signaling. These effects were also correlated with both mutagenesis
      and a predisposition to UVB-induced cell death but were unique to SP, because
      neither the SP metabolites canrenone and 7alpha-thiomethylspironolactone nor the
      more specific mineralocorticoid receptor antagonist eplerenone affected XPB
      protein levels or the UVB response. Our findings provide an approach for studying
      XPB and its roles in the UVB DNA damage response in human skin ex vivo and
      indicate that SP may increase UVB mutagenesis and skin cancer risk in certain
      individuals.

PMID- 30227141
TI  - Increased Myeloid Dendritic Cells and TNF-alpha Expression Predicts Poor Response
      to Hydroxychloroquine in Cutaneous Lupus Erythematosus.
AB  - Although antimalarials are the primary treatment for cutaneous lupus
      erythematosus, not all patients are equally responsive. We investigated whether
      different inflammatory cell population and cytokine profiles in lesional
      cutaneous lupus erythematosus skin could affect antimalarial responsiveness, and
      whether hydroxychloroquine (HCQ) and quinacrine (QC) differentially suppress
      inflammatory cytokines. Cutaneous lupus erythematosus patients were grouped
      according to their response to antimalarials (HCQ vs. HCQ+QC). On
      immunohistochemistry, only the myeloid dendritic cell population was
      significantly increased in the HCQ+QC group compared to HCQ group. While the IFN
      scores calculated for the selected type I IFN-regulated genes (LYE6, OAS1, OASL,
      ISG15, and MX1) were significantly higher in the HCQ group than the HCQ+QC group,
      the TNF-alpha level was higher in the HCQ+QC group. QC was more effective than
      HCQ at inhibiting the toll receptor-mediated production of TNF-alpha and IL-6 in
      the peripheral blood mononuclear cells isolated from cutaneous lupus
      erythematosus patients, whereas QC and HCQ inhibited IFN-alpha equally. QC also
      suppressed phospho-NF-kappaB p65 more profoundly than HCQ. In conclusion,
      increased myeloid dendritic cell population with higher TNF-alpha expression
      might contribute to HCQ refractoriness and a better response to QC. Differential
      suppressive effects of HCQ and QC could also affect antimalarial responses in
      cutaneous lupus erythematosus patients.

PMID- 30227142
TI  - Neural coding: A single neuron's perspective.
AB  - What any sensory neuron knows about the world is one of the cardinal questions in
      Neuroscience. Information from the sensory periphery travels across synaptically
      coupled neurons as each neuron encodes information by varying the rate and timing
      of its action potentials (spikes). Spatiotemporally correlated changes in this
      spiking regimen across neuronal populations are the neural basis of sensory
      representations. In the somatosensory cortex, however, spiking of individual (or
      pairs of) cortical neurons is only minimally informative about the world. Recent
      studies showed that one solution neurons implement to counteract this information
      loss is adapting their rate of information transfer to the ongoing synaptic
      activity by changing the membrane potential at which spike is generated. Here we
      first introduce the principles of information flow from the sensory periphery to
      the primary sensory cortex in a model sensory (whisker) system, and subsequently
      discuss how the adaptive spike threshold gates the intracellular information
      transfer from the somatic post-synaptic potential to action potentials,
      controlling the information content of communication across somatosensory
      cortical neurons.

PMID- 30227143
TI  - Addiction and stress: An allostatic view.
AB  - Allostasis, or stability through change, has most often been linked with
      challenges to homeostasis, in which repeated challenges or stressors produce
      sufficient allostatic load to generate an allostatic state that can ultimately
      lead to a disease state. The present review argues that the impact of stress on
      drug addiction fits with an allostatic model and represents a challenge to brain
      circuit regulatory mechanisms that underlie the emotional state of the animal.
      The central thesis is that stress leads to changes in corticotropin-releasing
      factor in the brain that impact addiction. Stress is further argued to impact all
      three stages of the addiction cycle-binge/intoxication, withdrawal/negative
      affect, and preoccupation/anticipation-exposing the animal to an emotional
      allostatic load and allostatic state that forms the growing motivational
      pathology of addiction. Viewing addiction as an allostatic mechanism provides key
      insights into the ways in which dysregulated neurocircuitry that is involved in
      basic motivational systems can transition to pathophysiology.

PMID- 30227145
TI  - Automated high-throughput individual tracking system for insect behavior:
      Applications on memory retention in parasitic wasps.
AB  - BACKGROUND: Insects are important models to study learning and memory formation
      in both an ecological and neuroscience context due to their small size,
      behavioral flexibility and ecological diversity. Measuring memory retention is
      often done through simple time-consuming set-ups, producing only a single
      parameter for conditioned behavior. We wished to obtain higher sample sizes with
      fewer individuals to measure olfactory memory retention more efficiently. NEW
      METHOD: The high-throughput individual T-maze uses commercially available
      tracking software, Ethovision XT(r), in combination with a Perspex stack of
      plates as small as 18 * 18 cm, which accommodates 36 olfactory T-mazes, where
      each individual wasp could choose between two artificial odors. Various
      behavioral parameters, relevant to memory retention, were acquired in this set
      up; first choice, residence time, giving up time and zone entries. From these
      parameters a performance index was calculated as a measure of memory retention.
      Groups of 36 wasps were simultaneously tested within minutes, resulting in
      efficient acquisition of sufficiently high sample sizes. RESULTS: This system was
      tested with two very different parasitic wasp species, the larval parasitoid
      Cotesia glomerata and the pupal parasitoid Nasonia vitripennis, and has proven to
      be highly suitable for testing memory retention in both these species. COMPARISON
      WITH EXISTING METHODS: Unlike other bioassays, this system allows for both high
      throughput and recording of detailed individual behavior. CONCLUSIONS: The high
      throughput individual T-maze provides us with a standardized high-throughput,
      labor-efficient and cost-effective method to test various kinds of behavior,
      offering excellent opportunities for comparative studies of various aspects of
      insect behavior.

PMID- 30227144
TI  - Limitations of platform assays to measure serum 25OHD level impact on guidelines
      and practice decision making.
AB  - CONTEXT: Liquid Chromatography Mass Spectroscopy (LC-MS/MS) is the preferred
      method to measure 25 hydroxyvitamin D (25OHD) levels, but laboratories are
      increasingly adopting automated platform assays. OBJECTIVE: We assessed the
      performance of commonly used automated immunoassays, with that of LC-MS/MS, and
      the National Institute of Standards and Technology (NIST) reference values, to
      measure 25OHD levels. METHODS/SETTING: We compared serum 25OHD levels obtained
      from 219 elderly subjects, enrolled in a vitamin D trial, using the Diasorin
      Liaison platform assay, and the tandem LC-MS/MS method. We also assessed the
      performance of the Diasorin and Roche automated assays, expressed as mean % bias
      from the NIST standards, based on the vitamin D External Quality Assessment
      Scheme (DEQAS) reports, from 2013 to 2017. RESULTS: Serum 25OHD levels were
      significantly lower in the Diasorin compared to LC-MS/MS assay at baseline, 18.5
      +/- 7.8 vs 20.5 +/- 7.6 ng/ml (p < 0.001), and all other time points. Diasorin
      (25OHD) = 0.76 * LC-MS/MS (25OHD) + 4.3, R2 = 0.596. The absolute bias was
      independent of 25OHD values, and the pattern unfit for any cross-calibration. The
      proportion of subjects considered for vitamin D treatment based on pre-set cut
      offs differed significantly between the 2 assays. There also was wide variability
      in the performance of both automated assays, compared to NIST reference values.
      CONCLUSION: The performance of most widely used automated assays is sub-optimal.
      Our findings underscore the pressing need to re-consider current practices with
      regard to 25OHD measurements, interpretation of results from research studies,
      meta-analyses, the development of vitamin D guidelines, and their relevance to
      optimizing health.

PMID- 30227146
TI  - Whole genome analysis of a novel picornavirus related to the
      Enterovirus/Sapelovirus supergroup from porcine feces in Japan.
AB  - A novel virus related to the Enterovirus/Sapelovirus supergroup in the family
      Picornaviridae was identified in healthy porcine feces in Japan by using a
      metagenomics approach. The genome of the virus, named Sapelo-like porcine
      picornavirus Japan (SPPVJ) Pig/Isi-Im1/JPN/2016, had a type-IV internal ribosomal
      entry site and carried a 6978-nucleotide-long single open reading frame encoding
      a 2326 amino acids (aa) polyprotein precursor. The coding sequence region
      consisted of leader protein (68 aa), a structural protein region P1 (824 aa), and
      the non-structural protein regions P2 (672 aa) and P3 (762 aa). Among
      representative picornaviruses, the P1, 2C, and 3CD regions of SPPVJ had the
      highest aa identities of 64.4%, 61.9%, and 73.3%, respectively, with the
      corresponding regions of sapelo-like bat picornavirus BtVs-PicoV/SC2013.
      Sequencing analysis of the RT-PCR products derived from the 5' untranslated and
      3D regions revealed the presence of SPPVJ in 17.8% (19/107) of the feces from
      healthy and diarrheal pigs in 12 farms in 2015-2016. Further studies are needed
      to determine the origin and pathogenic potential of SPPJV in pigs and other
      mammals.

PMID- 30227147
TI  - Expectations may influence the effects of transcranial direct current
      stimulation.
AB  - Growing interest surrounds transcranial direct current stimulation (tDCS) as a
      safe and inexpensive method for improving cognitive functions and mood.
      Nevertheless, tDCS studies rarely examine psychological factors such as
      expectations of outcomes, which may influence tDCS responsiveness through placebo
      like effects. Here we sought to evaluate the potential influence of expectations
      on tDCS intervention outcomes. We assessed expectations of tDCS outcomes in 88
      healthy young adults on three occasions: i) at baseline; ii) after reading
      information implying either high or low effectiveness of stimulation; and iii)
      after a single-session of sham-controlled anodal tDCS applied to the left
      dorsolateral prefrontal cortex, during working memory (WM) training. Participants
      were largely uncertain about the effectiveness of stimulation in improving
      cognitive function at baseline. High or low expectation priming using simple
      positive or cautionary messages significantly increased or decreased expectation
      ratings, respectively, but ratings significantly decreased following stimulation
      in all groups. We found greater improvement in participants who received high
      compared to low expectation priming. Participants who received active stimulation
      and low expectation priming exhibited the lowest performance, suggesting that
      expectation priming and stimulation may have interacted. We did not find a
      significant effect of baseline expectations, belief of group assignment, or
      individual characteristics on measures of WM and verbal fluency. However,
      controlling for baseline expectations revealed greater post-intervention
      improvement on the executive function measures in participants who received high
      (compared to low) expectation priming. People randomly assigned to receive high
      expectation priming reported having a more pleasant experience overall, including
      greater satisfaction. Our findings suggest that expectations of outcomes should
      be taken into account in tDCS-based experimental studies and clinical trials.

PMID- 30227148
TI  - Incubation of feeding behavior is regulated by neuromedin U receptor 2 in the
      paraventricular nucleus of the hypothalamus.
AB  - A diet of energy-dense food, characterized mainly as a high-fat diet, leads to a
      persistent excessive consumption defined as overeating. According to the National
      Institute of Health, more than 2 in 3 adults in the United States are overweight
      or obese, straining our healthcare system with epidemic proportions. Diets that
      include abstaining from high-fat foods, ironically, result in an increase in
      motivation and craving for said high-fat foods, defined as an incubation effect
      because the behavior aids in developing overeating. Previously, we have shown
      that modulation of neuromedin U receptor 2 (NMUR2) in the paraventricular nucleus
      of the hypothalamus (PVN) results in increased food intake and motivation for
      energy-dense foods. Here, we continue our focus on NMUR2 in the PVN, but in
      relation to the incubation effect on craving for high-fat food. We employed a
      model for incubation of craving by having rats abstain from high-fat foods for 30
      days before undergoing intake of fatty food on fixed ratio and progressive ratio
      schedules of reinforcement, and then assess their response to reactivity to cues.
      Using this model, we compared the feeding behaviors of rats that underwent an
      mRNA knockdown of the NMUR2 in the PVN to controls after both underwent a 30-day
      abstinence from high-fat foods. Our results show knockdown of NMUR2 in the PVN
      blocks the incubation of feeding behavior for food-related cues and high-fat
      foods.

PMID- 30227149
TI  - Incomplete block of NMDA receptors by intracellular MK-801.
AB  - NMDA receptors (NMDARs) are essential components in glutamatergic synaptic
      signaling. The NMDAR antagonist MK-801 has been a valuable pharmacological tool
      in evaluating NMDAR function because it binds with high affinity to the NMDAR ion
      channel pore and is non-competitive with ligand binding. MK-801 has also been
      used to selectively inhibit NMDAR current in only the cell being recorded by
      including the drug in the intracellular recording solution. Here, we report that
      intracellular MK-801 (iMK-801) only partially inhibits synaptic NMDAR currents at
      +40 mV at both cortical layer 4 to layer 2/3 and hippocampal Schaffer collateral
      to CA1 synapses. Furthermore, iMK-801 incompletely inhibits heterologously
      expressed NMDAR currents at -60 mV, consistent with a model of iMK-801 having a
      very slow binding rate and consequently ~30,000 times lower affinity than MK-801
      applied to the extracellular side of the receptor. While iMK-801 can be used as a
      qualitative tool to study reduced postsynaptic NMDAR function, it cannot be
      assumed to completely block NMDARs at concentrations typically used in
      experiments.

PMID- 30227150
TI  - Blast-induced "PTSD": Evidence from an animal model.
AB  - A striking observation among veterans returning from the recent conflicts in Iraq
      and Afghanistan has been the co-occurrence of blast-related mild traumatic brain
      injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI might
      coexist due to additive effects of independent psychological and physical traumas
      experienced in a war zone. Alternatively blast injury might induce PTSD-related
      traits or damage brain structures that mediate responses to psychological
      stressors, increasing the likelihood that PTSD will develop following a
      subsequent psychological stressor. Rats exposed to repetitive low-level blasts
      consisting of three 74.5 kPa exposures delivered once daily for three consecutive
      days develop a variety of anxiety and PTSD-related behavioral traits that are
      present for at least 9 months after blast exposure. A single predator scent
      challenge delivered 8 months after the last blast exposure induces additional
      anxiety-related changes that are still present 45 days later. Because the blast
      injuries occur under general anesthesia, it appears that blast exposure in the
      absence of a psychological stressor can induce chronic PTSD-related traits. The
      reaction to a predator scent challenge delivered many months after blast exposure
      suggests that blast exposure in addition sensitizes the brain to react abnormally
      to subsequent psychological stressors. The development of PTSD-related behavioral
      traits in the absence of a psychological stressor suggests the existence of blast
      induced "PTSD". Findings that PTSD-related behavioral traits can be reversed by
      BCI-838, a group II metabotropic glutamate receptor antagonist offers insight
      into pathogenesis and possible treatment options for blast-related brain injury.

PMID- 30227151
TI  - The PPARdelta agonist GW0742 restores neuroimmune function by regulating Tim-3
      and Th17/Treg-related signaling in the BTBR autistic mouse model.
AB  - Autism spectrum disorders (ASD) are neurodevelopmental disorders that are
      characterized by repetitive behaviors, and impairments in communication and
      social interaction. Studies have shown that activation of peroxisome proliferator
      activated receptor-delta (PPARdelta) causes anti-inflammatory effects in animal
      models of neuroinflammatory diseases. We investigated the possible anti
      inflammatory effect of a PPARdelta agonist, GW0742 in the BTBR T+ Itpr3tf/J
      (BTBR) mouse model of autism. BTBR and C57BL/6 (B6) mice were treated orally with
      GW0742 (30 mg/kg, p.o., once daily) for 7 days. Effect of GW0742 treatment on
      repetitive behavior, marble burying, and thermal sensitivity response was
      assessed on day 8. We further examined the effect of GW0742 treatment on
      immunological parameters in splenocytes using flow cytometry (CD4+TIM-3+, IL
      17A+TIM-3+, IL-17A+CD4+, RORgammaT+TIM-3+, RORgammaT+CD4+, Stat3+TIM-3+,
      Foxp3+TIM-3+, Foxp3+CD4+, and IFN-gamma+CD4+). We also explored the effects of
      GW0742 on mRNA and protein expression of TIM-3, IL-17A, RORgammaT, Stat3, IFN
      gamma, Foxp3, and IL-10 in the brain tissue using RT-PCR and western blot
      analyses. GW0742 treatment substantially decreased repetitive behaviors, and
      lowered thermal sensitivity response in BTBR mice. GW0742 attenuated the
      expression of inflammatory markers such as IL-17A, RORgammaT, Stat3, TIM-3, and
      IFN-gamma, while upregulating anti-inflammatory markers such as IL-10/Foxp3 both
      in the brain and periphery of BTBR mice. In conclusion, this study suggests that
      GW0742 corrects neurobehavioral dysfunction in BTBR mice which is concurrent with
      modulation of multiple signaling pathways.

PMID- 30227152
TI  - Resin infiltration: An effective adjunct strategy for managing high caries risk-A
      within-person randomized controlled clinical trial.
AB  - OBJECTIVES: Micro-invasive resin-infiltration has shown to inhibit lesion
      progression of proximal non-cavitated carious lesions, suggesting an alternative
      to early operative treatment. This split-mouth, randomized placebo-controlled
      clinical trial evaluated the effects of proximal lesion infiltration
      supplementary to standard-of-care management in high caries risk (HCR)-patients.
      METHODS: Forty-two HCR-subjects with two similar interproximal posterior lesions
      received professional HCR-regimen including repeated F-varnish applications. Two
      affected E2/D1-surfaces were randomized and concurrently treated by resin
      infiltration or mock-infiltration (control). Individually standardized digital
      radiographs provided visual determination of lesion-size distribution at baseline
      and 2-year follow-up. Data were analyzed by logistic regression and McNemar's
      test. RESULTS: Thirty-two lesion pairs (76%) were evaluated after 2 years.
      Categorical lesion depths were not different between groups (P > .5). Comparative
      pairwise assessment (image sets BL-2 yr) showed significantly more progression in
      control (7) versus infiltration (1) lesions (P = .035). Cumulative prevented
      fraction after two years was 97% for infiltrated lesions versus 74% for control
      lesions. CONCLUSIONS: Two-year follow-up showed resin infiltration to be a highly
      efficacious (RRR: 86-89%) therapy. Long-term follow-up is needed to strengthen
      the evidence for efficacy of resin-infiltration as an adjunct to standard-of-care
      HCR-regimen including F-varnish. CLINICAL SIGNIFICANCE: Showing 24% more
      stabilized lesions, the resin-infiltrated group performed significantly better
      than their controls, confirming successful early lesion management. Adjunct resin
      infiltration provided an effective micro-invasive approach to inhibit short-term
      lesion progression.

PMID- 30227153
TI  - New therapies for human cytomegalovirus infections.
AB  - The recent approval of letermovir marks a new era of therapy for human
      cytomegalovirus (HCMV) infections, particularly for the prevention of HCMV
      disease in hematopoietic stem cell transplant recipients. For almost 30 years
      ganciclovir has been the therapy of choice for these infections and by today's
      standards this drug exhibits only modest antiviral activity that is often
      insufficient to completely suppress viral replication, and drives the selection
      of drug-resistant variants that continue to replicate and contribute to disease.
      While ganciclovir remains the therapy of choice, additional drugs that inhibit
      novel molecular targets, such as letermovir, will be required as highly effective
      combination therapies are developed not only for the treatment of
      immunocompromised hosts, but also for congenitally infected infants. Sustained
      efforts, largely in the biotech industry and academia, have identified additional
      highly active lead compounds that have progressed into clinical studies with
      varying levels of success and at least two have the potential to be approved in
      the near future. Some of the new drugs in the pipeline inhibit new molecular
      targets, remain effective against isolates that have developed resistance to
      existing therapies, and promise to augment existing therapeutic regimens. Here,
      we will describe some of the unique features of HCMV biology and discuss their
      effect on therapeutic needs. Existing drugs will also be discussed and some of
      the more promising candidates will be reviewed with an emphasis on those
      progressing through clinical studies. The in vitro and in vivo antiviral
      activity, spectrum of antiviral activity, and mechanism of action of new
      compounds will be reviewed to provide an update on potential new therapies for
      HCMV infections that have progressed significantly in recent years.

PMID- 30227154
TI  - d-Fenfluramine and lorcaserin inhibit the binge-like feeding induced by MU-opioid
      receptor stimulation of the nucleus accumbens in the rat.
AB  - Multiple laboratories have shown that the stimulation of MU-opioid receptors in
      the nucleus accumbens (NAcc) powerfully increases intake of palatable and high
      fat diets. Separate studies have demonstrated that serotonin agonists advance
      satiety processes, and several serotonin-targeting agents have been prescribed to
      promote weight loss. However, it is unknown if serotonin signaling can modulate
      the increased feeding elicited by activation of NAcc MU-opioid receptors. These
      experiments assessed the effects of systemic treatments with the serotonin
      agonists d-fenfluramine and lorcaserin on the binge-like feeding induced by MU
      opioid receptor stimulation of the NAcc in Sprague-Dawley rats. Consistent with
      previous reports, stimulation of NAcc MU-opioid receptors (with 0.025 MUg/0.5
      MUl/side DAMGO) significantly increased consumption of high-fat vegetable
      shortening, and systemic treatment with d-fenfluramine and lorcaserin dose
      dependently decreased intake. Interestingly, d-fenfluramine and lorcaserin
      reversed the binge-like feeding observed following stimulation of NAcc MU-opioid
      receptors. Both serotonergic drugs also attenuated the increases of ambulation
      observed following administration of DAMGO in the NAcc. These data demonstrate
      that serotonergic anorectics, in addition to their known role in advancing
      satiety processes during normal feeding, can also inhibit the binge-like feeding
      that is elicited by activation of MU-opioid receptors within the ventral
      striatum.

PMID- 30227155
TI  - Dorsal premotor cortex is related to recognition of verbal and visual
      descriptions of actions in the first-person perspective.
AB  - This fMRI study examined whether the perspective difference of a verbally and
      visually descripted action stimulus (i.e., sentence and picture) modulates
      activity in the motor-related area. The participants were presented with a
      sentence (e.g., "I grasp an apple" or "You grasp an apple") or a picture (e.g., a
      picture of grasping an apple in which a right hand appears from the bottom or
      from the top) as the experimental task. A full factorial analysis of variance
      model with stimulus modality (verbal vs. visual description) and perspective
      (first- vs. second-person perspective) was used. The fMRI results showed greater
      activity in the left dorsal premotor cortex in the first-person perspective than
      in the second-person perspective for both the verbal and visual descriptions. The
      results suggest that motor representation is more strongly recruited with the
      recognition of an action-related stimulus descripted in the first-person
      perspective than in the second-person perspective, independent of stimulus
      modality.

PMID- 30227156
TI  - Trends in active transportation and associations with cardiovascular disease risk
      factors among U.S. adults, 2007-2016.
AB  - Active transportation (AT), or walking or bicycling for transportation,
      represents one way individuals can achieve recommended physical activity (PA)
      levels. This study describes AT prevalence and temporal trends, and examines
      associations between AT levels and measured CVD risk factors (hypertension,
      hypercholesterolemia, low high-density [HDL] cholesterol, diabetes, and obesity)
      among U.S. adults. National Health and Nutrition Examination Survey (NHANES) 2007
      2016 data (analyzed in 2017) were used to conduct overall trend analyses of
      reported AT in a typical week [none (0-9 min/week); low (10-149 min/week); or
      high (>=150 min/week)]. Logistic regression was used to examine associations
      between AT level and each CVD risk factor from NHANES 2011-2016 (n = 13,943).
      Covariates included age, sex, race/Hispanic origin, education, income, smoking,
      survey cycle, non-transportation PA, and urbanization level. U.S. adults who
      engaged in high AT levels increased from 13.1% in 2007-2008 to 17.9% in 2011
      2012, and then decreased to 10.6% in 2015-2016 (p for quadratic trend = 0.004).
      Over the same period, the quadratic trend for low AT was not significant. During
      2011-2016, 14.3% of adults engaged in high AT, 11.4% in low AT, and 74.4% in no
      AT. High AT levels were associated with decreased odds of each CVD risk factor
      assessed, compared to no AT. Low AT (versus no AT) was associated with decreased
      odds of hypertension (aOR = 0.77, 95% CI 0.64, 0.91) and diabetes (aOR = 0.68,
      95% CI 0.54, 0.85). AT prevalence among adults has fluctuated from 2007 to 2016.
      Despite favorable associations between AT and CVD risk factors, most U.S. adults
      do not engage in any AT.

PMID- 30227157
TI  - Glucagon-like peptide-1 receptor action in the vasculature.
AB  - Glucagon-like peptide-1 receptor (GLP-1R) agonists augment insulin secretion and
      are thus used clinically to improve glycemia in subjects with type 2 diabetes
      (T2D). As recent data reveal marked improvements in cardiovascular outcomes in
      T2D subjects treated with the GLP-1R agonists liraglutide and semaglutide in the
      LEADER and SUSTAIN-6 clinical trials respectively, there is growing interest in
      delineating the mechanism(s) of action for GLP-1R agonist-induced
      cardioprotection. Of importance, negligible GLP-1R expression in ventricular
      cardiac myocytes suggests that cardiac-independent actions of GLP-1R agonists may
      account for the reduced death rates from cardiovascular causes in T2D subjects
      enrolled in the LEADER trial. Conversely, vascular smooth muscle cells (VSMCs)
      appear to express the canonical GLP-1R, and GLP-1/GLP-1R agonists exhibit a
      number of salutary actions on the vascular endothelium that could potentially
      contribute to GLP-1R agonists directly improving cardiovascular outcomes in
      subjects with T2D. We review herein the described actions of GLP-1/GLP-1R
      agonists on the vascular endothelium, which include antiproliferative actions on
      VSMCs and endothelial cells, reductions in oxidative stress, and increases in
      nitric oxide generation. GLP-1 also increases microvascular recruitment and
      microvascular blood flow. Taken together, such actions may explain the
      antihypertensive and/or antiatherosclerotic actions attributed to GLP-1/GLP-1R
      agonists in preclinical and clinical studies. Nonetheless, further mechanistic
      studies are still necessary to determine the relative importance of such actions
      in accounting for reductions in macrovascular cardiovascular disease in human
      subjects with T2D treated with GLP-1R agonists.

PMID- 30227158
TI  - Conversion of a soluble diazepam prodrug to supersaturated diazepam for rapid
      intranasal delivery: Kinetics and stability.
AB  - The low aqueous solubility of diazepam (DZP) presents a challenge in formulating
      nasal sprays without the use of organic solvents. One approach to overcome this
      challenge involves co-administration of a soluble prodrug, avizafone (AVF), with
      a converting enzyme to produce supersaturated DZP at the site of administration.
      In addition to overcoming solubility issues, the supersaturated state of DZP
      provides an increased driving force for enhanced permeation across nasal mucosa.
      However, supersaturated solutions are metastable, and there is a limit to the
      degree of supersaturation (S) that can be reached without causing spontaneous
      phase separation of the solute. The aim of this article was to determine how
      formulation parameters affect the rate of DZP supersaturation, maximum degree of
      supersaturation, and phase separation kinetics. A model enzyme, Aspergillus
      oryzae protease (AOP), was used to convert AVF to DZP, via an open ring
      intermediate (ORI). A second derivative UV spectroscopic method was developed to
      simultaneously monitor DZP solution concentration and the time course of DZP
      phase separation. Fitting a kinetic model, with prior knowledge of the enzyme
      kinetic parameters, the rate constant for conversion of ORI to DZP was found to
      be 0.470 +/- 0.012 min-1. Kinetics and supersaturated solution stability were
      studied as a function of formulation parameters, including temperature, pH,
      buffering agent, AVF concentration, and enzyme concentration. The maximum aqueous
      solution concentration for DZP at 32  degrees C was determined to be 1.22 +/-
      0.03 mM DZP (S = 9.38) and was insensitive to changes in formulation parameters,
      excepting temperature. Supersaturated solutions of DZP could be maintained at the
      maximum concentration for >24 h, even in the presence of phase separated DZP.
      Polarized light microscopy, PXRD, and DSC analysis indicated that the phase
      separated DZP was amorphous upon formation and remained so for >24 h. Our
      findings suggest that co-administration of AVF with a suitable human converting
      enzyme will provide a viable mechanism for IN delivery of DZP and result in very
      rapid and complete absorption to quickly terminate seizure emergencies.

PMID- 30227159
TI  - Using elongated microparticles to enhance tailorable nanoemulsion delivery in
      excised human skin and volunteers.
AB  - This study demonstrates, for the first time, clinical testing of elongated silica
      microparticles (EMP) combined with tailorable nanoemulsions (TNE) to enhance
      topical delivery of hydrophobic drug surrogates. Likewise, this is the first
      report of 6-carboxyfluorescein (a model molecule for topically delivered
      hydrophobic drugs) AM1 & DAMP4 (novel short peptide surfactants) used in
      volunteers. The EMP penetrates through the epidermis and stop at the dermal
      epidermal junction (DEJ). TNE are unusually stable and useful because the oil
      core allows high drug loading levels and the surface properties can be easily
      controlled. At first, we chose alginate as a crosslinking agent between EMP and
      TNE. We initially incorporated a fluorescent lipophilic dye, DiI, as a
      hydrophobic drug surrogate into TNE for visualization with microscopy. We
      compared four different coating approaches to combine EMP and TNE and tested
      these formulations in freshly excised human skin. The delivery profile
      characterisation was imaged by dye- free coherent anti-Stoke Raman scattering
      (CARS) microscopy to detect the core droplet of TNE that was packed with
      pharmaceutical grade lipid (glycerol) instead of DiI. These data show the EMP
      penetrating to the DEJ followed by controlled release of the TNE. Freeze-dried
      formulations with crosslinking resulted in a sustained release profile, whereas a
      freeze-dried formulation without crosslinking showed an immediate burst-type
      release profile. Finally, we tested the crosslinked TNE coated EMP formulation in
      volunteers using multiphoton microscopy (MPM) and fluorescence-lifetime imaging
      microscopy (FLIM) to document the penetration depth characteristics. These forms
      of microscopy have limitations in terms of image acquisition speed and imaging
      area coverage but can detect fluorescent drug delivery through the superficial
      skin in volunteers. 6-Carboxyfluorescein was selected as the fluorescent drug
      surrogate for the volunteer study based on the similarity of size, charge and
      hydrophobicity characteristics to small therapeutic drugs that are difficult to
      deliver through skin. The imaging data showed a 6-carboxyfluorescein signal deep
      in volunteer skin supporting the hypothesis that EMP can indeed enhance the
      delivery of TNE in human skin. There were no adverse events recorded at the time
      of the study or after the study, supporting the use of 6-carboxyfluorescein as a
      safe and detectable drug surrogate for topical drug research. In conclusion, dry
      formulations, with controllable release profiles can be obtained with TNE coated
      EMP that can effectively enhance hydrophobic payload delivery deep into the human
      epidermis.

PMID- 30227160
TI  - Dynamic control of neural stem cells by bHLH factors.
AB  - During brain development, neural stem cells change their competency to give
      sequential rise to neurons and glial cells. Expression of the basic helix-loop
      helix (bHLH)-type cell-fate determination factors Ascl1, Olig2, and Hes1 is
      oscillatory in neural stem cells. Conversely, sustained expression of these
      factors mediates cell-fate determination. Optogenetic analyses suggest that
      oscillatory expression regulates maintenance and proliferation of neural stem
      cells, and that sustained expression induces cell-fate determination. Expression
      of the Notch ligand Delta-like1 (Dll1), which is controlled by Hes1 and Ascl1, is
      also oscillatory in neural stem cells. Mathematical modeling showed that if the
      timing of Dll1 expression is changed, Hes1 oscillations are severely dampened,
      resulting in impaired maintenance and proliferation of neural stem cells and
      causing microcephaly. Another bHLH factor, Hes5, also shows oscillatory
      expression in neural stem cells. Hes5 overexpression and knock-out result in
      abnormal expression of Hmga1 and Hmga2, which are essential for timing the
      switching of neural stem-cell competency. These data indicate that oscillatory
      expression of bHLH factors is important for normal neural stem-cell function in
      the developing nervous system.

PMID- 30227161
TI  - Temporal patterning of neocortical progenitor cells: How do they know the right
      time?
AB  - During mammalian neocortical development, neural progenitor cells undergo
      sequential division to produce different types of progenies. Regulation of when
      and how many cells with a specific fate are produced from neural progenitor
      cells, i.e., 'temporal patterning' for cytogenesis, is crucial for the formation
      of the functional neocortex. Recently advanced techniques for transcriptome
      profiling at the single-cell level provide a solid basis to investigate the
      molecular nature underlying temporal patterning, including examining the
      necessity of cell-cycle progression. Evidence has indicated that cell-intrinsic
      programs and extrinsic cues coordinately regulate the timing of both the change
      in the division mode of neural progenitors from proliferative to neurogenic and
      their laminar fate transition from deep-layer to upper-layer neurons. Epigenetic
      modulation, transcriptional cascades, and post-transcriptional regulation are
      reported to function as cell-intrinsic programs, whereas extrinsic cues from the
      environment or surrounding cells supposedly function in a negative feedback or
      positive switching manner for temporal patterning. These findings suggest that
      neural progenitor cells have intrinsic temporal programs that can progress cell
      autonomously and cell-cycle independently, while extrinsic cues play a critical
      role in tuning the temporal programs to let neural progenitor cells know the
      'right' time to progress.

PMID- 30227162
TI  - Elucidating the developmental trajectories of GABAergic cortical interneuron
      subtypes.
AB  - GABAergic interneurons in the neocortex play pivotal roles in the feedforward and
      feedback inhibition that control higher order information processing and thus,
      malfunction in the inhibitory circuits often leads to neurodevelopmental
      disorders. Very interestingly, a large diversity of morphology, synaptic
      targeting specificity, electrophysiological properties and molecular expression
      profiles are found in cortical interneurons, which originate within the distantly
      located embryonic ganglionic eminences. Here, I will review the still ongoing
      effort to understand the developmental trajectories of GABAergic cortical
      interneuron subtypes.

PMID- 30227163
TI  - Timing matters: A strategy for neurons to make diverse connections.
AB  - Neurogenesis proceeds like a continuous wave, in which each type of neurons is
      produced over a few days to several days. During this protracted time window,
      early-born and late-born neurons are sequentially produced with a considerable
      time lag. Even if they are identical in their genetic and molecular
      specifications, they could develop different characteristics under the influences
      of the timing of their birth. In this review, we discuss the potential influences
      of "timing" as a generic parameter affecting neuronal differentiation,
      particularly on axon guidance and connections. These ideas have rarely been
      tested experimentally, but may provide a new strategy by which phenotypic
      diversity is increased in neurons.

PMID- 30227164
TI  - Triple play of DYRK1A kinase in cortical progenitor cells of Trisomy 21.
AB  - Down syndrome (DS) also known as Trisomy 21 is a genetic disorder that occurs in
      ~1 in 800 live births. The disorder is caused by the triplication of all or part
      of human chromosome 21 and therefore, is thought to arise from the increased
      dosage of genes found within chromosome 21. The manifestations of the disease
      include among others physical growth delays and intellectual disability. A
      prominent anatomical feature of DS is the microcephaly that results from altered
      brain development. Recent studies using mouse models of DS have shed new light on
      DYRK1A (dual-specificity tyrosine-phosphorylation-regulated kinase 1A), a gene
      located on human chromosome 21 that plays a critical role in neocortical
      development. The present review summarizes effects of the increased dosage of
      DYRK1A on the proliferative, neurogenic and astrogliogenic potentials of cortical
      neural progenitor cells, and relates these findings to the clinical
      manifestations of the disease.

PMID- 30227165
TI  - Temporal patterning of neurogenesis and neural wiring in the fly visual system.
AB  - During neural development, a wide variety of neurons are produced in a highly
      coordinated manner and form complex and highly coordinated neural circuits.
      Temporal patterning of neuron type specification plays very important roles in
      orchestrating the production and wiring of neurons. The fly visual system, which
      is composed of the retina and the optic lobe of the brain, is an outstanding
      model system to study temporal patterning and wiring of the nervous system. All
      of the components of the fly visual system are topographically connected, and
      each ommatidial unit in the retina corresponds to a columnar unit in the optic
      lobe. In the retina, the wave of differentiation follows the morphogenetic
      furrow, which progresses in a posterior-to-anterior direction. At the same time,
      differentiation of the optic lobe also accompanies the wave of differentiation or
      temporally coordinated neurogenesis. Thus, temporal patterning plays important
      roles in establishing topographic connections throughout the fly visual system.
      In this article, we review how neuronal differentiation and connectivity are
      orchestrated in the fly visual system by temporal patterning mechanisms.

PMID- 30227166
TI  - Prefrontal circuit organization for executive control.
AB  - The essential role of executive control is to select the most appropriate
      behavior among other candidates depending on the sensory information (exogenous
      information) and on the subject's internal state (endogenous information). Here I
      review series of the evidence implicating that the rodent prefrontal cortex (PFC)
      evaluates and compares the expected outcome for candidate actions that are
      automatically primed by exogenous and endogenous information, and selects the
      most appropriate action while inhibiting the others, with different PFC
      subregions contributing to distinct aspects of the computation via differential
      recruitments of the distributed networks. The recurrent nature of the PFC
      networks further facilitates the computation by integrating bottom-up signals
      over a long timescale. I also overview the local circuit organization in the PFC,
      where vasoactive intestinal peptide-positive (VIP) GABAergic interneurons are
      tightly linked with the cholinergic system and play significant roles in
      regulating executive control signals. The empirical evidence inspires the
      disinhibitory module hypothesis of the PFC organization that a group of pyramidal
      neurons and interneurons forms a disinhibitory module with similar task-variable
      selectivity in the PFC, and long-range inputs and neuromodulations in these
      modules exert a distributed gain modulation of the ongoing executive control
      signals by adjusting VIP neuron activity.

PMID- 30227167
TI  - Molecular mechanisms of H3K27me3 and H3K4me3 in retinal development.
AB  - The retina consists of six types of neuron and Muller glia, and they are
      individually derived from common retinal progenitors in a chronologically defined
      order. Therefore, the signaling environment and competency of retinal progenitors
      change during retinal development, and the retina serves as an excellent model
      system to analyze molecular events during development. Much attention has been
      given to the identification of transcription factors and epigenetic mechanisms.
      The dynamic changing of the histone modification levels of retina-specific genes
      has been observed, and the modification patterns of H3K4me3 and H3K27me3 are
      regulated in a retinal cell type-specific manner. Therefore, it appears that the
      dynamism of histone modification in the developing retina is regulated both
      chronologically and in a cell type-specific manner in a particular gene category.
      Loss- and gain-of-function analyses of enzymes involved in the methylation and
      demethylation of H3K4 and K27 in the retina have indicated their critical roles
      in proliferation, differentiation, and determinations of the timing for
      differentiation. We summarize recent findings related to the roles of H3K4me3 and
      H3K27me3 in retinal development to discuss how the retinal system provides
      intriguing data on and contributes to concepts regarding the roles of histone
      modification in the chronological regulation of tissue development.

PMID- 30227168
TI  - Multiple roles of the actin and microtubule-regulating formins in the developing
      brain.
AB  - Dynamic control of the actin and microtubule cytoskeletons underlie nearly every
      critical process during neural development, and requires multiple dimensions of
      regulation. Formins are a family of fifteen proteins that functions as a major
      class of linear actin nucleators and regulates both actin and microtubule
      dynamics. The fact that several closely-related formins show complementary
      expression patterns during neural development and non-overlapping cytoskeletal
      functions indicates the need to identify the specialized cellular activities of
      individual formin members in different neural cell subtypes. In this review, we
      briefly introduce the known biochemical and regulatory functions of formins in
      the context of neural development, and summarize their cellular functions in the
      developing brain.

PMID- 30227169
TI  - Amino acid profile in women with gestational diabetes mellitus treated with
      metformin or insulin.
AB  - AIMS: We compared the effects of metformin and insulin treatments of gestational
      diabetes mellitus (GDM) on amino acid metabolism. METHODS: 217 pregnant women
      diagnosed with GDM were randomized to receive either metformin or insulin. 1H
      nuclear magnetic spectroscopy was used to determine serum concentrations of
      alanine, glutamine, glycine, isoleucine, leucine, valine, histidine,
      phenylalanine, tyrosine, glucose and lactate at the time of diagnosis and at 36
      gestational weeks (gw). RESULTS: Majority of the amino acid concentrations
      increased from 30 to 36 gw. The rise in alanine (16% vs. 8%, p < 0.0001),
      isoleucine (11% vs. 5%, p = 0.035) and lactate (29% vs. 14% p = 0.015) was larger
      in the metformin group compared to insulin group. Baseline alanine, glycine,
      isoleucine, leucine, valine and tyrosine were positively related to slightly
      earlier delivery. Alanine at 36 gw was positively associated with birth weight
      and glutamine with gestational hypertension or preeclampsia. Lactate at 36 gw was
      not associated with any adverse outcome. CONCLUSIONS: Compared to insulin
      metformin caused a greater increase in serum alanine, isoleucine and lactate
      concentrations. Although the observed differences in the metabolic variables were
      relatively small and not outright concerning, additional studies and follow-up
      data are required to ensure the safety of metformin use in pregnancy. The trial
      was registered in Clinicaltrials.gov, NCT01240785;
      http://clinicaltrials.gov/ct2/show/NCT01240785.

PMID- 30227170
TI  - C679X loss-of-function PCSK9 variant lowers fasting glucose levels in a black
      South African population: A longitudinal study.
AB  - AIMS: To determine the longitudinal association of the loss-of-function (LOF)
      PCSK9 variants (C679X and A443T), proxies of PCSK9 inhibitor drugs, with LDL-C,
      fasting glucose and glycated hemoglobin. METHODS: We conducted a five year,
      longitudinal study, nested within the Prospective Urban and Rural Epidemiology
      study, among 737 apparently healthy, male and female black South Africans of the
      North West province. Genotyping of the C679X and A443T PCSK9 variants was
      achieved using Taqman assays from Applied Biosystems. Generalized estimating
      equations were used to determine longitudinal association of the A443T and C679X
      PCSK9 variants with LDL-C, fasting glucose and glycated hemoglobin. RESULTS:
      C679X and A443T variant carriers were associated with significant reductions in
      LDL-C of -0.98(-1.29, -0.67) mmol/L; p < 0.001) and -0.39(-0.57, -0.20) mmol/L; p
      < 0.001) respectively, compared to the non-carriers. Only C679X variant was
      independently associated with reductions in fasting glucose of -0.37 (-0.61, 
      0.13) mmol/L; p = 0.002) compared to non-carriers. However, the association of
      the selected variants with glycated hemoglobin were not significant. C679X and
      A443T carriers were associated with -0.07 (-0.23, 0.09) %; p = 0.400), 0.05 (
      0.13, 0.22) %; p = 0.599) of glycated haemoglobin respectively. CONCLUSION: Our
      results indicated that carriers of A443T and C679X variants exhibit sustained low
      LDL-C levels over 5 years and have varied effects on T2D biomarkers compared to
      non-carriers.

PMID- 30227172
TI  - Thymoquinone prevents cisplatin neurotoxicity in primary DRG neurons.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a substantial, dose-limiting
      adverse effect that occurs in cancer patients. Cis-dichlorodiamine (II) platinum
      (CDDP, cisplatin) is a platinum-based chemotherapeutic agent that causes severe
      acute and chronic peripheral neuropathies in 30% of cancer patients. Thymoquinone
      (TQ), a leading bioactive constituent of Nigella sativa seeds, has been reported
      to have antioxidant, anti-inflammatory, anti-neoplastic and neuroprotective
      properties. Dorsal root ganglia (DRG) include different classes of primary
      sensory neurons, such as nociceptors, mechanoreceptors, and proprioceptive
      neurons. Here, we investigated the neuroprotective activity of TQ against
      cisplatin neurotoxicity in cultured DRG neurons. We prepared neuronal cultures
      from DRGs of adult mice, pre-treated them with or without varying doses of TQ
      prior to exposure of cells to cisplatin. The preparations were viewed under the
      scope before and after the treatment at 24 h, 48 h, and 72 h time points. We
      analyzed neuronal cell viability and neurite outgrowths, and evaluated
      morphologic changes of neuronal or non-neuronal cells. TQ significantly increases
      the ability to extend neurites and neuronal cell viability when compared to the
      culture conditions which were treated with cisplatin only. Although we provide
      compelling evidence for the protective activity of TQ against chemotherapy
      induced neurotoxicity, further detailed investigations in preclinical settings
      are warranted for its clinical use.

PMID- 30227171
TI  - ARL3 subcellular localization and its suspected role in autophagy.
AB  - ADP-ribosylation factor-like3 (ARL3) is a member of the ADP-ribosylation factor
      family of GTP-binding proteins that plays important role in regulating Ciliary
      trafficking. It ubiquitously expressed in normal tissues and tumor cell lines.
      However, the location and function of ARL3 in organelles are rarely known. In
      this study, we explored ARL3 subcellular localization in an all-round way in
      HEK293T, Neuro-2A and U251 cells by density gradient centrifugation and
      immunofluorescence. The results showed that ARL3 is expressed in most of
      organelles, and an iodixonal step gradient was further confirmed that ARL3 is
      mainly localized to the mitochondria, endosomes, lysosomes, and proteasome. By
      molecular functional analysis, we observed that ARL3 promotes the aggregation of
      GFP-LC3, up-regulation of LC3-II/LC3-I and down-regulation of SQSMT1/BECN1, and
      knocking down of ARL3 inbibits autophagy, which suggested that ARL3 is necessary
      for autophagy. this study presents a comprehensive evaluation of the subcellular
      localization for ARL3 and provides important on understanding the functions of
      ARL3.

PMID- 30227173
TI  - Modeling of cigarette smoke constituents - From intense to less intense smoking
      regime.
AB  - Since it was first required to measure and to report NFDPM and nicotine yields in
      a limited number of countries, there has been an increasing trend for more
      testing and reporting requirements. Historically, the ISO 3308 smoking regime has
      been used to determine NFDPM and nicotine yields. However recommendations from
      the World Health Organization, now include the use of two smoking regimes such as
      the ISO 3308 and the WHO TobLabNet Official Method SOP01, the latter being
      considered as an intense smoking regime. Considering the increase in data
      produced and similarities between some smoke constituents formed during
      combustion, we explored possible correlations between emissions under intense and
      less intense smoking conditions. A set of 22 commercial cigarettes was tested.
      Eighty five smoke constituents were determined under both intense and less
      intense regimes. In addition 36 tobacco constituents, 14 cigarette design
      parameters and eight cigarette burning features were determined. A computational
      process was designed to implement multiple linear regression analyses enabling
      the identification of the best subsets of explanatory variables among emissions
      under intense conditions, cigarette design parameters, tobacco constituents and
      burning parameters. We succeeded in building simple linear models, involving four
      to six variables, while reaching satisfactory goodness of fit and R-squared
      values ranging from 0.87 to 1.00. Our findings suggest, in the range of products
      tested, that the additional data gained by using a second smoking regime does not
      necessarily increase the volume of information and consequently does not
      necessarily improve knowledge. This study supports the premise that the
      application of two smoking regimes does not produce a more comprehensive product
      characterisation compared to using one.

PMID- 30227175
TI  - Oxidative stress responses in human bronchial epithelial cells exposed to
      cigarette smoke and vapor from tobacco- and nicotine-containing products.
AB  - The use of novel tobacco- and nicotine-containing vapor products that do not
      combust tobacco leaves is on the rise worldwide. The emissions of these products
      typically contain lower numbers and levels of potentially harmful chemicals
      compared with conventional cigarette smoke. These vapor products may therefore
      elicit fewer adverse biological effects. We compared the effects of emissions
      from different types of such products, i.e., our proprietary novel tobacco vapor
      product (NTV), a commercially available heat-not-burn tobacco product (HnB), and
      e-cigarette (E-CIG), and a combustible cigarette in a human bronchial epithelial
      cell line. The aqueous extract (AqE) of the test product was prepared by bubbling
      the produced aerosol into medium. Cells were exposed to the AqEs of test
      products, and then glutathione oxidation, Nrf2 activation, and secretion of IL-8
      and GM-CSF were examined. We found that all endpoints were similarly perturbed by
      exposure to each AqE, but the effective dose ranges were different between
      cigarette smoke and the tobacco- and nicotine-containing vapors. These results
      demonstrate that the employed assays detect differences between product
      exposures, and thus may be useful to understand the relative potential biological
      effects of tobacco- and nicotine-containing products.

PMID- 30227174
TI  - In vitro test systems to determine tetracycline residue binding to human feces.
AB  - The use of antimicrobials, such as tetracycline, in food-producing animals may
      result in antimicrobial drug residues (ADR) in edible tissues from treated
      animals and contribute to the emergence of antibiotic resistant bacteria. The
      Veterinary International Conference on Harmonization (VICH) document (VICH
      GL36(R)/FDA-CVM Guidance for Industry#159) provides guidance on evaluating the
      safety of veterinary ADR in the human foods as related to effects on the human
      intestinal microbiome. One recognized research gap is a need for additional data
      and testing requirements to determine the fraction of an oral dose of ADR
      available to intestinal microorganisms. In the present study, we address this
      need by examining the binding of tetracycline to human feces using chemical and
      microbiological assays. High-performance liquid chromatography and liquid
      chromatography mass spectrometry assays showed that 25% (w/v) diluted steam
      sterilized feces dosed with 0.15 and 1.5 MUg/ml tetracycline had binding of 58.2
      +/- 10.8% and 56.9 +/- 9.1%, respectively. Tetracycline binding to fecal slurries
      gave similar results. Microbiological assays with two reference bacterial strains
      validated the results of the chemical assays. Based on data from chemical and
      microbiological assays methods, the fraction of dose available to microorganisms
      was 0.418 and 0.431 of the 0.15 and 1.5 MUg/ml tetracycline treatments,
      respectively. This study also proposes factors to be considered when designing
      and conducting experiments to determine the percent of an antimicrobial agents
      that is available to microorganisms in the gastrointestinal tract.

PMID- 30227176
TI  - Surgical Hints for Robot-Assisted Transvesical Simple Prostatectomy.
AB  - OBJECTIVES: To report a step-by-step technique for robot-assisted transvesical
      simple prostatectomy (RASP) focusing on surgical hints to facilitate the
      procedure. METHODS: From January 2014 to April 2018 the institutional database
      was queried for consecutive patients undergoing RASP performed by a single
      surgeon. Procedures were performed according to standardized steps as reported in
      the accompanying video. Ports were placed in a 'W' configuration. Surgery started
      with the bladder detachment, then the endopelvic fascia was exposed. The bladder
      neck was incised in a longitudinal fashion. Exposure of the adenoma was aided by
      using Keith needles. The bladder mucosa was incised and the dissection of the
      adenoma was performed till complete adenomectomy. Hemostasis of the enucleation
      bed was performed with electrocauterization. A 2-0 Polysorb suture was used for
      accomplishing the trigonization. Bladder closure was performed in double layer. A
      Foley catheter was inserted, then a water-tightness test was performed. Specimen
      was retrieved via the incision for the optical port. RESULTS: Twenty-eight
      patients were performed, according to the described technique. Median prostate
      volume was 180 cm3. Median blood losses were 200 mL. No intraoperative
      complications were recorded. Four patients had minor complications (14%). Median
      catheterization time was 8 days. Regarding functional outcomes, patients had
      significant improvement of Qmax, postvoided residual volume, and international
      prostate symptom score at postoperative control (P < .001). CONCLUSION: RASP is
      feasible, safe and effective, and represents a viable approach to large adenomas.
      Prospective comparison with alternative minimally-invasive endoscopic techniques
      is warranted.

PMID- 30227177
TI  - Regional white matter volume abnormalities in first-episode somatization
      disorder.
AB  - BACKGROUND: Alterations of white matter integrity have been implicated in
      patients with somatization disorder (SD). However, changes of white matter volume
      (WMV) remain unclear. This study is designed to examine regional WMV in patients
      with SD and to investigate the potential relationships between WMV abnormalities
      and personality traits, cognitive function, and symptom severity. METHODS: We
      recruited 25 first-episode, drug-naive patients with SD and 28 sex-, age-, and
      education-matched healthy controls for the study. Personality traits, cognitive
      function, and symptom severity were assessed for all participants. Data were
      analyzed with the computational anatomy toolbox (CAT12) methods. RESULTS:
      Patients with SD exhibited a significantly increased WMV in the right inferior
      frontal gyrus (IFG) (t = 4.4009) and a significantly decreased WMV in the left
      inferior longitudinal fasciculus (ILF) (t = -3.4292) relative to healthy
      controls. No correlation was found between abnormal WMV and clinical/cognitive
      variables in the patients. CONCLUSIONS: Our findings suggest the presence of
      significant regional WMV abnormalities in first-episode, drug-naive patients with
      SD, which might improve understanding the pathophysiology of SD.

PMID- 30227178
TI  - Bcl2L12 plays a critical role in the development of airway allergy via inducing
      aberrant T helper-2 polarization.
AB  - Bcl2L12 plays an important role in the pathogenesis of allergic asthma by
      promoting the differentiation of Th2 cells, which may be a novel therapeutic
      target in the treatment of allergic asthma.

PMID- 30227179
TI  - LRP4 antibody positive amyotrophic lateral sclerosis patients display neuropil
      reactive IgG and enhanced serum complement levels.

PMID- 30227180
TI  - Human nostril hair: Optimised follicular penetration for initiating early immune
      responses?

PMID- 30227181
TI  - Enniatin B induces expression changes in the electron transport chain pathway
      related genes in lymphoblastic T-cell line.
AB  - Enniatin B is a ionophoric and lipophilic mycotoxin which reaches the bloodstream
      and has the ability to penetrate into cellular membranes. The purpose of this
      study was to reveal changes in the gene expression profile caused by enniatin B
      in human Jurkat lymphoblastic T-cells after 24 h of exposure at 1.5, 3 and 5 MUM
      by next generation sequencing. It was found that up to 27% of human genome
      expression levels were significantly altered (5750 genes for both down-regulation
      and up-regulation). In the three enniatin B concentrations studied 245
      differentially expressed genes were found to be overlapped, 83 were down and 162
      up-regulated. ConsensusPathDB analysis of over-representation of differentially
      expressed genes provided a list of gene ontology terms in which several
      biological processes related to nucleoside monophosphate metabolic process,
      respiratory chain complex, electron transport chain, oxidative phosphorylation
      and cellular respiration were the most altered. Also, an interesting correlation
      was found between enniatin B toxicity and the up-regulation of the UCP protein
      complex. In summary, the transcriptomic analysis revealed that mitochondria are
      the organelles showing more related differentially expressed genes. Consequently,
      differentially expressed genes involved in biological processes, molecular
      functions and pathways related to mitochondrial metabolism and respiration were
      significantly changed.

PMID- 30227182
TI  - Development of the Highly Processed Food Withdrawal Scale.
AB  - Food addiction posits that highly processed foods may be capable of triggering
      addictive-like symptoms in some individuals, including withdrawal. The current
      study developed and assessed the psychometric properties of the first self-report
      measure of highly processed food withdrawal. Individuals (n = 231) aged 19-68
      (51.9% female) were recruited online through Amazon Mechanical Turk and reported
      cutting down on highly processed foods in the past year. The Highly Processed
      Food Withdrawal Scale (ProWS) was adapted from self-report measures of drug
      withdrawal and internal consistency and validity were evaluated. Paralleling the
      course of drug withdrawal, symptoms assessed by the ProWS were reported as most
      intense between days 2-5 during an attempt to cut down. The ProWS demonstrated
      convergent validity with addictive-like eating (r = 0.48, p < .001), body mass
      index (BMI) (r = 0.16, p = .02), and weight cycling (r = 0.29, p < .001) and
      discriminant validity with dietary restraint: (r = -0.13, p = .04). The ProWS
      explained 11.2% of variance in self-reported success in last diet attempt beyond
      addictive-like eating and BMI. The ProWS seems to be a psychometrically sound
      tool for future research investigating highly processed food withdrawal in
      humans, and the present data may provide preliminary insight into the
      plausibility of withdrawal symptoms occurring in response to cutting down on
      highly processed foods.

PMID- 30227183
TI  - Too picky for my taste? The effect of the gluten-free dietary restriction on
      impressions of romantic partners.
AB  - Millions of individuals world-wide adhere to a gluten-free diet and this dietary
      trend is on the rise. The present research identified a consumption stereotype of
      those following a gluten-free diet and tested whether this stereotype influenced
      impressions and interest in a potential romantic partner. We also assessed
      whether being gluten-free differentially impacted impressions of males compared
      to females. In Study 1, participants (N = 161) responded to a survey containing
      both qualitative and quantitative components in which they evaluated gluten-free
      individuals and indicated their interest in dating them. In Study 2 (N = 132), we
      manipulated the dietary restriction (gluten-free vs. no dietary restriction) of a
      target within the context of a mock online dating paradigm and measured
      participants' evaluations of the target. In both studies, gluten-free individuals
      were perceived as having positive and negative attributes such as being high
      maintenance, picky, demanding, complaining and judgmental, yet healthy, self
      disciplined, understanding and energetic. The gluten-free diet was associated
      with ratings of femininity and lead to more negative judgments of males than
      females. Whereas in Study 1 participants expressed some hesitation about dating a
      gluten-free individual, no effects on romantic interest were obtained in Study 2.
      These data are the first to delineate the gluten-free stereotype and provide a
      useful platform for future study.

PMID- 30227184
TI  - The psychology of vegetarianism: Recent advances and future directions.
AB  - Whereas vegetarianism has long garnered attention from nutritional science and
      philosophy, psychological research exploring this eating behavior has emerged
      only in the past few decades. Six years ago, Ruby (2012) reviewed the extant
      literature on the psychology of vegetarianism, showcasing its promise as "a
      blossoming field of study." In the time since, this line of research truly has
      blossomed, as subsequent work has addressed prior knowledge gaps and initiated
      new lines of inquiry. While evidence on previously studied topics of dietary
      motivation, moral values, gender, differences between vegetarians and vegans,
      barriers to dietary change, and disordered eating has continued to expand, new
      lines of research on identity, social experiences, flexitarianism, culture, and
      prospective vegetarianism have emerged. Recent psychometric advancements,
      moreover, have constructed useful measures to assess relevant constructs. The
      current review synthesizes this amalgam of research, identifying emergent themes
      and highlighting promising directions for future inquiry.

PMID- 30227185
TI  - Temporal Changes in a Novel Metric of Physical Activity Tracking (Personal
      Activity Intelligence) and Mortality: The HUNT Study, Norway.
AB  - BACKGROUND: Personal Activity Intelligence (PAI) is a novel activity metric that
      translates heart rate variations during exercise into a weekly score. Weekly PAI
      scores assessed at a single point in time were found to associate with lower risk
      of premature cardiovascular disease (CVD) mortality in the general healthy
      population. However, to date, the associations between long-term longitudinal
      changes in weekly PAI scores and mortality have not been explored. PURPOSE: The
      aim of the present study was to prospectively examine the association between
      change in weekly PAI scores estimated 10 years apart, and risk of mortality from
      CVD and all-causes. METHODS: We performed a prospective cohort study of 11,870
      men and 13,010 women without known CVD in Norway. By using data from the Nord
      Trondelag Health Study (HUNT), PAI was estimated twice, ten years apart (HUNT1
      1984-86 and HUNT2 1995-97). Mortality was followed-up until December 31, 2015.
      Adjusted hazard ratios (AHR) and 95% confidence intervals (CI) for death from CVD
      and all-causes related to temporal changes in PAI were estimated using Cox
      regression analyses. RESULTS: During a mean (SD) of 18 (4) years of follow-up,
      there were 4782 deaths, including 1560 deaths caused by CVD. Multi-adjusted
      analyses demonstrated that participants achieving a score of >=100 PAI at both
      time points had 32% lower risk of CVD mortality (AHR 0.68; CI: 0.54-0.86) for CVD
      mortality and 20% lower risk of all-cause mortality (AHR 0.80; CI: 71-0.91)
      compared with participants obtaining <100 weekly PAI at both measurements. For
      participants having <100 PAI in HUNT1 but >=100 PAI in HUNT2, the AHRs were 0.87
      (CI: 0.74-1.03) for CVD mortality, and 0.86 (CI: 0.79-0.95) for all-cause
      mortality. We also found an inverse linear relationship between change in PAI and
      risk of CVD mortality among participants with 0 PAI (P < 0.01), and <=50 PAI (P =
      0.04) in HUNT1, indicating that an increase in PAI over time is associated with
      lower risk of mortality. Excluding the first three years of follow-up did not
      substantially alter the findings. Increasing PAI score from <100 PAI in HUNT1 to
      >=100 PAI in HUNT2 was associated with 6.6 years gained lifespan. CONCLUSION:
      Among men and women without known CVD, an increase in PAI score and sustained
      high PAI score over a 10-year period was associated with lower risk of mortality.

PMID- 30227186
TI  - Long-term Outcomes of the Arterial Switch Operation for d-Transposition of the
      Great Arteries.
AB  - Dextrotransposition of the great arteries (d-TGA) is a relatively rare form of
      complex childhood congenital heart disease, which occurs in approximately 0.2 in
      1000 live births (Long et al, 2010). The most common palliative procedure for
      this anatomy has become the arterial switch operation (ASO). We will review in
      this paper the evidence that is currently available regarding the clinical
      management following the ASO. Individuals with d-TGA who undergo ASO at a young
      age thus far have excellent long-term outcomes. Long-term complications for the
      ASO should be monitored for and patients should have routine follow-up with
      specialists in adult congenital heart disease.

PMID- 30227187
TI  - Meta-analysis of Exercise Training on Left Ventricular Ejection Fraction in Heart
      Failure with Reduced Ejection Fraction: A 10-year Update.
AB  - BACKGROUND: The role of exercise training modality to attenuate left ventricular
      (LV) remodeling in heart failure patients with reduced ejection fraction (HFrEF)
      remains uncertain. The authors performed a systematic review and meta-analysis of
      published reports on exercise training (moderate-intensity continuous aerobic,
      high-intensity interval aerobic, and resistance exercise) and LV remodeling in
      clinically stable HFrEF patients. METHODS: We searched MEDLINE, Cochrane Central
      Registry of Controlled Trials, CINAHL, and PubMed (2007 to 2017) for randomized
      controlled trials of exercise training on resting LV ejection fraction (EF) and
      end-diastolic and end-systolic volumes in HFrEF patients. RESULTS: 18 trials
      reported LV ejection fraction (LVEF) data, while 8 and 7 trials reported LV end
      diastolic and LV end-systolic volumes, respectively. Overall, moderate-intensity
      continuous training (MICT) significantly increased LVEF (weighted mean
      difference, WMD = 3.79%; 95% confidence interval, CI, 2.08 to 5.50%) with no
      change in LV volumes versus control. In trials >=6 months duration, MICT
      significantly improved LVEF (WMD = 6.26%; 95% CI 4.39 to 8.13%) while shorter
      duration (<6 months) trials modestly increased LVEF (WMD = 2.33%; 95% CI 0.84 to
      3.82%). High-intensity interval training (HIIT) significantly increased LVEF
      compared to control (WMD = 3.70%; 95% CI 1.63 to 5.77%) but was not different
      than MICT (WMD = 3.17%; 95% CI -0.87 to 7.22%). Resistance training performed
      alone or combined with aerobic training (MICT or HIIT) did not significantly
      change LVEF. CONCLUSIONS: In clinically stable HFrEF patients, MICT is an
      effective therapy to attenuate LV remodeling with the greatest benefits occurring
      with long-term (>=6 months) training. HIIT performed for 2 to 3 months is
      superior to control, but not MICT, for improvement of LVEF.

PMID- 30227188
TI  - When Should Adult Congenital Heart Disease Patients be Considered for Transplant
      and Deciding Which Organs to Transplant.
AB  - The number of adult congenital heart disease (ACHD) patients continues to
      increase. Because of multiple related factors such as aging, residual cardiac
      lesions and prior palliative procedures, advanced heart failure (HF) is
      increasingly prevalent in this population. Consequently, there is an emerging
      need to determine which patients are best suited for advanced cardiac therapies,
      including heart transplantation (HT) and mechanical circulatory support.
      Unfortunately, optimizing patient selection for these therapies is complicated by
      patient heterogeneity, variable HF presentation across lesion-type, and a paucity
      of outcome data. The lack of patient specific data and the increasing number of
      ACHD patients with end-stage HF identifies a need to more precisely stratify risk
      and determine appropriate timing for referral. As such, this article will discuss
      the clinical recognition and classification of advanced HF in the ACHD patient
      populations and review current data regarding HT outcomes. Following, key
      considerations regarding the timing of HT in specific forms of ACHD, the role of
      device therapy, and when dual organ transplantation should be considered will be
      reviewed. Finally, existing knowledge gaps and key research needs will be
      highlighted.

PMID- 30227189
TI  - Assessment of clinician accuracy for diagnosing melanoma on basis of electrical
      impedance spectroscopy score plus morphology versus lesion morphology alone.

PMID- 30227190
TI  - Nodal Staging of High Risk Cutaneous Squamous Cell Carcinoma.
AB  - BACKGROUND: While progress has been made in defining the clinical and
      histopathologic features of high-risk cutaneous squamous cell carcinoma (HRcSCC),
      optimal staging guidelines remain elusive. OBJECTIVE: We seek to guide clinical
      practice regarding nodal staging options for patients with HRcSCC via review of
      evolving definitions of HRcSCC, nodal staging options and how nodal staging may
      impact treatment and affect outcomes. METHODS: Retrospective review of published
      peer-reviewed literature regarding risk stratification, nodal staging and
      treatment and outcomes for patients with HRcSCC via PubMed search. RESULTS: For
      patients without clinical lymphadenopathy, based on literature from head and neck
      SCC, pre-operative nodal staging with US may be more useful than CT or MRI. Since
      early nodal disease is usually curable, sentinel lymph node biopsy (SLNB) may be
      considered in those with negative imaging while we await studies of nodal staging
      outcomes. LIMITATIONS: More data is needed to validate the relationships between
      primary tumor stage and SLNB status and to determine if early detection of nodal
      disease impacts survival for patients with HRcSCC. CONCLUSION: It is reasonable
      to consider nodal staging for patients with HRcSCC (BWH stage T2b and T3) in the
      absence of clinically palpable lymphadenopathy via radiographic imaging and, if
      negative, SLNB.

PMID- 30227191
TI  - Rouleaux: a microscopic clue that helps distinguish psoriasis from dermatitis.

PMID- 30227192
TI  - Analysis of Dermatologic Procedures Billed Independently by Non-Physician
      Practitioners in the United States.
AB  - BACKGROUND: Non-physician practitioners (NPPS), including nurse practitioners
      (NPs) and physician assistants (PAs) are expanding their scope of practice
      outside of primary care and performing more procedures in dermatology. OBJECTIVE:
      To understand the scope and geographic pattern of practice by NPs and PAs in
      dermatology in the US. METHODS: Cross-sectional retrospective cohort analysis of
      dermatology practices in the 2014 Medicare Physician/Supplier Procedure Summary
      Master File, which reflects Part B carrier and durable medical equipment fee-for
      service claims in the US. RESULTS: Over 4 million procedures were billed
      independently by NPs and PAs, which accounts for 11.51% of all. Injection, simple
      repair, and biopsy were the most commonly billed by non-physician practitioners,
      but complex procedures were also increasingly billed independently by NPs and
      PAs. Proportions of their claims are higher in the East Coast, Midwest, and
      Mountain states. LIMITATIONS: Data is at the state level, limited to Medicare
      beneficiaries, and doesn't include billing incident-to physicians. CONCLUSIONS:
      This study demonstrated the increasing scope of practice of NPs and PAs in
      dermatology, despite limited training and lack of uniform regulations. To ensure
      quality and safety of care, it is prudent to set benchmarks for proper
      supervision and utilization of procedures in dermatology.

PMID- 30227193
TI  - Long-term safety results from a phase 3 open-label study of a fixed combination
      halobetasol propionate 0.01% and tazarotene 0.045% lotion in moderate-to-severe
      plaque psoriasis.

PMID- 30227195
TI  - In reply to Prognostic value of sentinel lymph node biopsy according to Breslow
      thickness for cutaneous melanoma.

PMID- 30227194
TI  - Long-term outcomes of laser treatment for congenital melanocytic nevus.
AB  - BACKGROUND: Although various laser treatments have been tried for CMNs, only
      small retrospective studies with short-term follow-up had been done to assess
      outcomes. OBJECTIVE: We analyzed the long-term outcomes of laser treatment for
      CMN and compared the outcomes with the combination treatment of partial excisions
      and lasers. METHODS: Patients with CMN treated with lasers were retrospectively
      reviewed and patients with more than 3-year follow-up were grouped as the long
      term follow-up group. RESULTS: A total of 67 cases of CMN were reviewed. Among 20
      patients (20/52, 38.5%) with nearly total clearance during laser-only treatment,
      11 patients were in long-term follow-up group and 5 of them showed
      repigmentation. 15 patients showed repigmentation regardless of clearance, and
      the mean period until repigmentation was 3.93 years from the initial treatment.
      Patients with combination treatment of partial excision and lasers showed higher
      Investigator's Global Assessment (IGA) scores, less number of laser treatments
      and shorter treatment period compared to patients with laser-only treatment.
      LIMITATIONS: This is a retrospective study and various laser devices were used.
      CONCLUSION: More than 4 years of follow-up is required to evaluate the efficacy
      of lasers in CMN and combination treatment of partial excision and lasers can be
      an effective treatment option.

PMID- 30227196
TI  - Safe and efficacious treatment of purpura with Nd:YAG laser in Skin Types IV-VI.

PMID- 30227197
TI  - Computational assessment of miRNA binding to low and high expression HLA-DPB1
      allelic sequences.
AB  - Cell surface expression of HLA-DP is allele specific. SNP rs9277534 (A/G),
      located in the 3'UTR of the DPB1 gene, has been associated with either low (A) or
      high (G) expression of DP on the cell surface. Considering the role of miRNAs in
      the regulation of gene expression, we computationally identified the miRNAs of
      two BLCLs, PGF and COX, predicted to interact with their corresponding DPB1
      transcripts, DPB1 * 04:01:01:01-low expression and DPB1 * 03:01:01:01-high
      expression. The identified target sequences are located primarily in intron 2 and
      the 3'UTR. We hypothesize that gene expression may be influenced first by nuclear
      pre-mRNA events involving intronic regions, followed by the usual 3'UTR
      associated events in the cytoplasm. The low DP expression allele was found to
      interact in silico with a larger number of miRNAs than the high expression
      allele. This pattern holds when examining either the entire transcript unit or
      simply the polymorphic sites that differentiate the alleles. Interestingly, the
      rs9277534 A/G polymorphism appears to be in linkage disequilibrium with
      polymorphisms targeted by the identified miRNAs. The multiplicity of sites
      targeted by different miRNAs suggests that the expression of DPB1 may be a
      dynamic process, influenced by different miRNAs under different states of the
      cell.

PMID- 30227198
TI  - The impact of radiation therapy on lymphocyte count and survival in metastatic
      cancer patients receiving PD-1 immune checkpoint inhibitors.
AB  - PURPOSE: Therapeutic radiation has conflicting immune effects: radiation (RT)
      induced immunogenic cell death can contribute to immune response, but lymphocytes
      are also sensitive to RT. It is unknown whether palliative RT leads to
      lymphopenia in patients treated with immune checkpoint inhibitors (ICI) and
      whether this impacts outcomes. As such, we sought to assess the impact of
      palliative RT on circulating lymphocyte count and neutrophil-lymphocyte-ratio
      (NTL) in patients being treated with PD-1 directed ICI and associations with
      survival. MATERIALS AND METHODS: We identified patients from five radiation
      oncology centers, treated with palliative RT and either pembrolizumab or
      nivolumab with non-small cell lung cancer (NSCLC), metastatic melanoma (MM), and
      renal cell carcinoma (RCC). Patients who received intervening cytotoxic
      chemotherapy were excluded. We recorded absolute lymphocyte count (ALC) and
      neutrophil to lymphocyte ratio (NTL) before and after palliative RT, and at the
      start of ICI. Survival was analyzed using the Kaplan-Meier method and Cox
      proportional hazard models. RESULTS: One hundred ten patients received 225
      courses of palliative RT. Median change in ALC (dALC) after RT was -161 cells/mL.
      Decreases in ALC were greater with RT to the spine, lung/mediastinum, and chest
      wall compared with the brain, extremity, or abdomen/pelvis (p=0.002), and after
      courses >5 fractions (p=0.003). Extracranial and >5 fraction radiation was
      associated with increased odds of severe lymphopenia (ALC<500) at the end of RT
      (OR 3.7, p=0.001, and OR 3.9 p=0.001, respectively). Patients who developed RT
      induced severe lymphopenia were more likely to have severe lymphopenia when ICI
      was initiated (OR 6.4, p=0.0001), particularly when RT was administered in the
      previous 3 months (OR 189, p<0.0001). Severe lymphopenia at onset of ICI therapy
      was associated with increased mortality on multivariable analysis (HR 2.1,
      p=0.03). CONCLUSIONS: Extracranial or prolonged courses of RT increase the risk
      of severe lymphopenia, which is associated with poorer survival in patients
      treated with ICI.

PMID- 30227200
TI  - Racemic phenylpropanoids from the root barks of Ailanthus altissima (Mill.)
      Swingle with cytotoxicity against hepatoma cells.
AB  - Four pairs of racemic phenylpropanoids (1a/1b-4a/4b), including five new
      compounds (1a/1b, 2a, 3a, and 4a) were obtained from the root barks of Ailanthus
      altissima (Mill.) Swingle. Their structures were determined by comprehensive
      spectroscopic analyses. The absolute configurations of the enantiomers were
      determined by comparison of the experimental ECD and OR with the calculated data.
      The antitumor activity of all isolates was evaluated against two human hepatoma
      carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that 1a/1b showed
      potent selective cytotoxicity against HepG2 cells. Additionally, 1a/1b could also
      induce apoptosis enantioselectively as demonstrated by Hoechst staining
      experiment.

PMID- 30227201
TI  - Inhibitory kinetics and mechanism of rifampicin on alpha-glucosidase: Insights
      from spectroscopic and molecular docking analyses.
AB  - alpha-Glucosidase is a critical enzyme associated with diabetes mellitus, and the
      inhibitors of the enzyme play important roles in the treatment of the disease. In
      this study, the inhibitory effect and mechanism of rifampicin on alpha
      glucosidase were investigated by multispectroscopic methods along with molecular
      docking technique. The results showed that rifampicin inhibited alpha-glucosidase
      activity prominently (IC50 = 135 +/- 1.2 MUM) in a reversible and competitive
      type manner. The fluorescence intensity of alpha-glucosidase was quenched by
      rifampicin through forming rifampicin-alpha-glucosidase complex in a static
      procedure. And the formation of the rifampicin-alpha-glucosidase complex was
      driven spontaneously by hydrophobic forces and hydrogen bonds. The results
      obtained from molecular docking further indicated that hydrophobic forces were
      formed between rifampicin and amino acid residues Phe 173, Pro151, and hydrogen
      bonds were generated by the interactions of rifampicin with residues Ser 180, Asn
      414, Gly160, and Gly161 of alpha-glucosidase. Moreover, it was found that the
      binding of rifampicin to alpha-glucosidase could alter the conformation of the
      enzyme to make it steady, and the binding distance was estimated to be 1.02 nm.
      Therefore, this study confirmed a novel alpha-glucosidase inhibitor and possibly
      contributed to the improvement of newfangled anti-diabetic agent.

PMID- 30227202
TI  - High-strength and self-recoverable silk fibroin cryogels with anisotropic
      swelling and mechanical properties.
AB  - Creating mechanically strong macroporous hydrogels with anisotropic properties as
      observed in many biological tissues is a major challenge in the gel science. Here
      we describe a directional freezing/cryogelation method of producing high-strength
      and rapid self-recoverable silk fibroin scaffolds with a high degree of
      mechanical anisotropy similar to that of tendon. By adjusting the synthesis
      parameters, we were able to create fibroin scaffolds exhibiting the highest
      modulus anisotropy so far reported, 21 +/- 5, with moduli E = 2.3 +/- 0.5 and
      0.11 +/- 0.03 MPa measured along parallel and perpendicular to the freezing
      direction, respectively. The cryogels are squeezable under load whereas, upon
      unloading, the squeezed-out water is taken back immediately. It was shown that
      the squeezability of the cryogels results in significant viscous stresses and
      energy dissipation. Cyclic mechanical tests reveal that the friction between the
      fibroin pore walls is the primary factor responsible for the energy dissipation.
      Independent on the fibroin concentration or direction of the measurements, 60% of
      the mechanical energy given to the cryogels are dissipated due to the friction
      between the pore walls, which is responsible for their almost complete
      squeezability and self-recoverability.

PMID- 30227199
TI  - Trajectories of pre- and postnatal co-use of cannabis and tobacco predict co-use
      and drug use disorders in adult offspring.
AB  - Co-use of cannabis and tobacco is increasingly common among women and is
      associated with tobacco and cannabis dependence and poorer cessation outcomes.
      However, no study has examined maternal patterns of co-use over time, or the
      impact of maternal co-use on co-use and drug problems in adult offspring.
      Pregnant women (M age = 23, range = 18-42; 52% African American, 48% White) were
      asked about substance use during each trimester of pregnancy, and at 8 and 18
      months, 3, 6, 10, 14, 16, and 22 years postpartum. We examined patterns of any
      maternal cigarette and cannabis use during pregnancy and the postpartum years. As
      young adults (M age = 22.8 years, range = 21-26), 603 offspring completed the
      Diagnostic Interview Schedule (DIS). Growth mixture modeling (GMM) was used to
      identify four maternal trajectories through 16 years postpartum: (1) no co-use
      (66%), (2) decreasing co-use (16%), (3) postpartum-only co-use (11%), and (4)
      chronic co-use (7%). Offspring whose mothers were in the decreasing co-use group
      (co-users primarily during prenatal and preschool periods) were more likely to be
      co-users than the offspring of non-co-users. Offspring whose mothers were chronic
      co-users of cigarettes and cannabis were more than twice as likely to have a drug
      use disorder than young adults whose mothers were not co-users. The results of
      this study highlight the heterogeneity in maternal co-use of tobacco and cannabis
      over time, with some women quitting during pregnancy but resuming co-use in the
      postpartum, and other women co-using during pregnancy but desisting co-use over
      time. Maternal trajectories of co-use were associated with inter-generational
      transfer of risk for substance use and dependence in adult offspring.

PMID- 30227203
TI  - Polysaccharides from tubers of Bletilla striata: Physicochemical
      characterization, formulation of buccoadhesive wafers and preliminary study on
      treating oral ulcer.
AB  - The purpose of this research is to arouse people's cognition of the dual role of
      Bletilla striata polysaccharide (BSP)-a kind of biocompatible, biodegradable
      natural biological materials with myriad pharmacological activities. BSP was
      extracted and characterized firstly. The results indicated that BSP was composed
      of mannose and glucose. The backbone of BSP mainly consisted of (1 -> 4)-linked
      beta-D-mannopyranose. Afterwards, A 32 factorial design was employed for
      optimization of lyophilized wafers for the treatment of traumatic oral ulcer with
      concentrations of BSP and glycerin as independent variables. Tensile strength,
      mucoadhesive strength, and swelling index were measured as response variables. It
      was determined that the wafer prepared from a solution containing 4% (w/v) BSP
      and 7% (w/v) glycerin was the optimal formulation. The wafers exhibited
      sufficient mechanical strength and suitable surface pH. Morphology of the wafers
      was observed. DSC/TGA thermograms showed the presence of three peaks weight loss
      events and decomposition patterns. Moreover, in vivo examinations indicated that
      the BSP wafer significantly promoted ulcer healing at 7 days, while no
      statistically significant difference was observed on day 12. In conclusion, this
      study suggests that BSP is an ideal biomaterial for mucosal adhesion agents,
      playing a nontrivial role in promoting oral ulcer healing.

PMID- 30227204
TI  - Effect of organic and inorganic salt environment on the complex coacervation of
      in situ formed protein nanoparticles and DNA.
AB  - Complex coacervation was noticed between in situ formed protein (a primarily
      hydrophobic Zein protein with pI = 6.2) nanoparticles (size 80-120 nm) and ds-DNA
      (a high charge density polyanion), in the ionic liquid (IL) solutions of 1-ethyl
      3-methyl imidazolium chloride [C2mim][Cl], and 1-octyl-3-methyl imidazolium
      chloride [C8mim][Cl], in the studied ionic strength range of I = 10-4 to 6 * 10-1
      M, which was extended to strong monovalent 1:1 electrolyte (NaCl) to explore the
      commonality between the organic and inorganic salt (ionic) environment on
      coacervation. The salt dependent coacervation profile was monitored from the
      measured turbidity of the interacting solution, and zeta potential, (zeta) and
      apparent hydrodynamic radius (Rh) of interpolymer complexes, which depicted the
      following three discernible interaction regimes common to all the salts: (i)
      Region-I: I = 0.0001-0.01 M, primary binding, (ii) Region-II, I = 0.01-0.1 M,
      secondary binding, and (iii) Region-III, I = 0.1-0.6 M, saturation binding. The
      free-energy and the network density calculations favored preferential
      coacervation in [C2mim][Cl] samples. Nonetheless, commonality in the overall
      ionic strength dependent coacervation profiles could still be observed.

PMID- 30227205
TI  - Elucidation of interaction mechanism of ellagic acid to the integrin linked
      kinase.
AB  - Integrin-linked kinase (ILK) is a member of Ser/Thr kinase which interacts to the
      cytoplasmic domain of beta-integrins, and thereby induces apoptosis. ILK is
      considered as potential drug target because it's direct involvement in the tumor
      progression. Here, we have performed molecular docking followed by 100 ns MD
      simulation to understand the mechanism of interaction of ILK with the ellagic
      acid (EA). EA is well known for its antiproliferative and antioxidant properties
      in cancer cell lines and animal models. We have observed that EA binds to the
      active site cavity of ILK and causes conformational changes in the ILK structure.
      The orientation of EA in the active pocket of ILK showed to have least RMSD
      values and stable. The average binding energy ILK-EA complex calculated during
      MMPBSA was -191.267 kJ/mol, indicating a relatively strong binding affinity. The
      actual binding affinity of EA to ILK was measured by fluorescence spectroscopy
      and Kb and n values were 9.28 MUM and 1.9264 (~2), respectively. The IC50 values
      for EA were 26.22 +/- 0.12 MUM for MCF-7 and 38.45 +/- 2.42 MUM for HepG2 cells,
      estimated by MTT assay. Our findings are helpful to design EA-based novel
      inhibitors of ILK which have potential to attenuate tumor progression.

PMID- 30227206
TI  - Analysis of DNA protection, interaction and antimicrobial activity of isatin
      derivatives.
AB  - Isatin, thiosemicarbazone and their derivatives have been widely used in
      biological applications such as antimicrobial, antiviral and anticancer
      therapies. Herein, eight isatin and thiosemicarbazone derivative compounds were
      re-synthesized and evaluated for DNA binding analysis including DNA protection
      studies using plasmid DNA (pUC19) and DNA interaction experiments using calf
      thymus DNA (CT-DNA). All compounds were also utilized in vitro assay to assess
      the antimicrobial activity of compounds against different pathogenic bacterial
      strains. All isatin and thiosemicarbazone derivative compounds exhibited DNA
      protection activity which ranged from 23.5 to 59.5%. Among them, I3-(N-2-MP)-TSC
      had the greatest DNA protective activity. For DNA binding analysis, all compounds
      had the same constant concentration (40 MUM), which interacts with CT-DNA. It was
      also observed that DNA interactions gave a high intrinsic binding constant (Kb =
      1.72 * 104 M-1-9.73 * 105 M-1). Besides, several derivatives of isatin
      thiosemicarbazone exhibited significant and selective antibacterial activity with
      low concentration. These compounds primarily affected Gram-positive bacteria, but
      were not effective against P. vulgaris and E. coli. The Gram-positive methicillin
      resistant S. aureus ATCC 43300 (MRSA) was the most influenced strain by these
      compounds. It was found that methyphenyl group at isatin was essential for its
      antibacterial activity for MRSA.

PMID- 30227207
TI  - alpha-Tocopherol liposome loaded chitosan hydrogel to suppress oxidative stress
      injury in cardiomyocytes.
AB  - Myocardial infarction (MI) continues to be a major contributor to the morbidity
      and mortality across the globe. Injectable hydrogel, a tissue-engineered
      scaffold, recently demonstrated very promising in myocardial repair. However, the
      undesirable retention and survival of transplanted cells has limited their
      applications due to the oxidative stress microenvironment of MI lesions. In this
      work, a thermosensitive alpha-tocopherol (AT) liposome loaded chitosan hydrogel
      was developed to suppress the oxidative stress injury in cardiomyocytes. AT was
      embedded in the liposomes to improve its solubility and stability. The innovative
      AT liposome loaded chitosan hydrogel (AT-LCH) system had an appropriate sol-to
      gel transition temperature. Hydrogels possessed a highly porous structure with
      irregular pores interconnected throughout the construct as shown by SEM, and
      liposomes distributed uniformly in the porous structure. A sustained AT release
      was observed in AT-LCH. In addition, AT-LCH has shown an excellent
      biocompatibility to support the adhesion and survival of cardiomyocytes.
      Moreover, it can resist the oxidative stress environment and improve the survival
      of cardiomyocytes. In general, this work suggests that AT-LCH may present an
      ideal scaffold material for injectable cardiac tissue engineering.

PMID- 30227208
TI  - Shikimic acid from Artemisia absinthium inhibits protein glycation in diabetic
      rats.
AB  - This study investigated the impact of Shikimic Acid (SA) obtained from leaves of
      Artemisia absinthium on protein glycation in the retina of diabetic rats. The
      GC/MS analysis of A. absinthium showed that the most abundant bioactive compound
      was SA (C7H10O5) with a measured retention Index (RI) of 1960 compared to that of
      the reference sample (1712). Male albino rats were divided into two main groups,
      Group I (control) and Group II (diabetic); Group II was further divided into four
      subgroups: Group IIa (diabetic control), Group IIb (diabetic rats were given SA
      orally [50 mg/kg, body weight (bw)/day], Group IIc diabetic rats were given SA
      orally [100 mg/kg, bw/day], and Group IId (diabetic rats were given metformin
      orally [100 mg/kg, bw/day] as positive control). The data obtained suggested that
      SA reduced glucose and glycated hemoglobin levels. In addition, SA also decreased
      the formation of glucose-derived advanced glycation end products. Interestingly,
      SA showed interference with the release of inflammatory mediators in retina and
      possess antioxidant potential. In conclusion, SA protected the tissues from
      detrimental effects of hyperglycemia and enhanced antioxidant activity. SA could
      be a potential lead in the process of drug development in the future to prevent
      retinopathy in diabetic subjects.

PMID- 30227209
TI  - Enhanced response of tamoxifen toward the cancer cells using a combination of
      chemotherapy and photothermal ablation induced by lentinan-functionalized multi
      walled carbon nanotubes.
AB  - A lentinan (LEN) functionalized multi-walled carbon nanotubes (MWCNTs) drug
      delivery system, using tamoxifen (TAM) as a model anticancer agent, was developed
      by a simple non-covalent approach. This developed system (MWCNTs-TAM-LEN)
      possessed good stability, water dispersibility and extraordinary photothermal
      properties. It was demonstrated by the in vitro experiments that MWCNTs-TAM-LEN
      had enhanced cellular uptake, antitumor activity and cell apoptosis on Mcf-7
      cells in comparison with TAM and MWCNTs-TAM. The cell inhibition rate and
      apoptosis rate of Mcf-7 cells treated by MWCNTs-TAM-LEN with near-infrared (NIR)
      were 67.1% and 66.5% higher than that of equivalent concentration of TAM with NIR
      irradiation treatment, respectively. The enhanced antitumor efficacy of MWCNTs
      TAM-LEN was realized via the synergistic function of chemotherapy and
      photothermal ablation under NIR laser irradiation.

PMID- 30227210
TI  - The first complete mitochondrial genome from the family Hygrophoraceae
      (Hygrophorus russula) by next-generation sequencing and phylogenetic
      implications.
AB  - Hygrophorus russula (Schaeff.) Kauffman is an edible ectomycorrhizal fungus that
      is widely distributed in the world. In this study, the mitogenome of H. russula
      was sequenced and assembled. The mitogenome of H. russula is composed of circular
      DNA molecules, with a total size of 55,769 bp. Further analysis indicated that
      the frequent use of A and T in codons contributes to the high AT content (80.87%)
      in the H. russula mitogenome. Comparative analysis indicated that the length and
      base composition of the core protein-encoding genes, and the number of tRNA genes
      in the H. russula mitogenome varied from that of other Agaricales mitogenomes.
      Gene arrangement analysis revealed a novel gene order in the H. russula
      mitogenome. In addition, the expansion of the mitogenome in Agaricales was found
      to be closely related to the increase in the number of introns. Phylogenetic
      analysis of the combined mitochondrial gene set showed strong support for tree
      topologies, and H. russula was determined to be relatively distant from other
      Agaricales species. This study is the first report on the mitogenome of a member
      of genus Hygrophorus as well as family Hygrophoraceae, which improves our
      understanding of mitochondrial differentiation and evolution in the important
      ectomycorrhizal fungi Hygrophorus species.

PMID- 30227212
TI  - Hybrid chitosan-ZnO nanoparticles coated with a sonochemical technique on silk
      fibroin-PVA composite film: A synergistic antibacterial activity.
AB  - The hybrid chitosan-ZnO nanoparticles (C@ZnO NPs) are synthesized and coated on
      Silk fibroin-polyvinyl alcohol (SF-PVA) composite film by a sonochemical coating
      process. These are systematically studied for their synergistic antibacterial
      activity and reported. The coated composite films show the excellent
      antibacterial activity against Gram-positive and Gram-negative bacteria. The
      composite films are characterized by using X-ray diffraction (XRD), Fourier
      transform infrared spectroscopy (FTIR), and Scanning Electron Microscopy (SEM)
      studies. The specific surface area and porosity are studied by Brunauer-Emmett
      Teller (BET) analysis under nitrogen gas adsorption. The swelling degree,
      mechanical property and cell viability study of coated and uncoated composite
      films are investigated. The results showed that the specific surface area,
      porosity, swelling degree, and mechanical property of coated composite films
      increased with increasing the concentrations of C@ZnO NPs on SF-PVA composite
      film. Cell viability study confirmed the cytocompatible nature of all the C@ZnO
      NPs coated composite films. Thus, obtained properties of composite films reveal
      the potential of this material which can be used as antibacterial wound dressing
      applications.

PMID- 30227211
TI  - Synthesis of mycotoxin protein IF8 by the entomopathogenic fungus Isaria
      fumosorosea and its toxic effect against adult Diaphorina citri.
AB  - Entomopathogenic fungi based microbial insecticides are considered as safe
      alternatives to chemical pesticides, which secretes several bioactive compounds
      to kill the host insects. In this study, we report a new approach for the
      synthesis and characterization of insecticide toxic protein IF8 produced by the
      Isaria fumosorosea 08, and to evaluate the mycotoxin level against the vector of
      Huanglongbing (HLB) or citrus greening disease, the Asian citrus psyllid,
      Diaphorina citri. Soluble toxic metabolites extracted from I. fumosorosea 08
      through submerged liquid state culture had a molecular weight of 43 kDa when
      subjected by to sodium dodecyl sulfate-poly-acrylamide (SDS-PAGE) gel
      electrophoresis. The most abundant of toxic protein IF8 was determined by High
      performance liquid chromatography (HPLC) and liquid chromatography electrospray
      ionization-mass spectroscopy (LC-ESI-MS) for the analysis of its molecular mass
      weight and purity. Further Matrix-assisted laser desorption ionization-time of
      flight (MALDI-TOFF) analysis confirmed the presence of toxic metabolites in
      liquid culture. Subsequently, mycotoxic effect of toxic protein IF8 was tested
      against D. citri at three different concentrations (1%, 2%, and 3%). The results
      showed the insecticidal activity of >80% when administered at three different
      concentrations at 48-120 hour post-application. Additionally, we also
      investigated the physicochemical properties and stability of IF8 by using
      computational biological tools. This is the first study to report the
      characterization of fungal mediated synthesis of the protein IF8 toxic to the
      insect D. citri. These results suggest the mycotoxin control of D. citri and
      prevention of HLB transmission by using a natural toxic compound which is eco
      friendly and can be potentially used for the integrated management of D. citri.

PMID- 30227213
TI  - METase promotes cell autophagy via promoting SNHG5 and suppressing miR-20a in
      gastric cancer.
AB  - BACKGROUND: Gastric cancer (GC) severely threatens human life, and METase seemed
      to inhibit tumor growth. However, the potential mechanism underlying it is still
      unclear. METHODS: Both clinical tissues and cell lines were used in the present
      study. SNHG5 and miR-20a expressions were determined using real-time PCR. Western
      blot was performed to determine the expression of autophagy-related proteins. The
      interaction between miR-20a and SNHG5 was determined using luciferase reporter
      assay and RNA immunoprecipitation (RIP). RESULTS: The expression of SNHG5 was
      decreased in GC tissues and cell lines. Overexpressed METase significantly
      promoted cell apoptosis and autophagy, as well as the expression of SNHG5. SNHG5
      directly regulated the expression of miR-20a. GC cells transfected with pcDNA
      SNHG5 significantly promoted cell apoptosis and autophagy, while the co
      transfected with miR-20a mimic dramatically reversed the effects of pcDNA-SNHG5.
      Overexpressed METase significantly promoted cell autophagy, which was abolished
      by down-regulated SNHG5. CONCLUSION: Overexpressed METase promoted cell apoptosis
      and autophagy via up-regulating the expression of SNHG5 and down-regulating miR
      20a in GC.

PMID- 30227214
TI  - Reassessment of the classification of Bryopsidales (Chlorophyta) based on
      chloroplast phylogenomic analyses.
AB  - The Bryopsidales is a morphologically diverse group of mainly marine green
      macroalgae characterized by a siphonous structure. The order is composed of three
      suborders - Ostreobineae, Bryopsidineae, and Halimedineae. While previous studies
      improved the higher-level classification of the order, the taxonomic placement of
      some genera in Bryopsidineae (Pseudobryopsis and Lambia) as well as the
      relationships between the families of Halimedineae remains uncertain. In this
      study, we re-assess the phylogeny of the order with datasets derived from
      chloroplast genomes, drastically increasing the taxon sampling by sequencing 32
      new chloroplast genomes. The phylogenies presented here provided good support for
      the major lineages (suborders and most families) in Bryopsidales. In
      Bryopsidineae, Pseudobryopsis hainanensis was inferred as a distinct lineage from
      the three established families allowing us to establish the family
      Pseudobryopsidaceae. The Antarctic species Lambia antarctica was shown to be an
      early-branching lineage in the family Bryopsidaceae. In Halimedineae, we revealed
      several inconsistent phylogenetic positions of macroscopic taxa, and several
      entirely new lineages of microscopic species. A new classification scheme is
      proposed, which includes the merger of the families Pseudocodiaceae, Rhipiliaceae
      and Udoteaceae into a more broadly circumscribed Halimedaceae, and the
      establishment of tribes for the different lineages found therein. In addition,
      the deep-water genus Johnson-sea-linkia, currently placed in Rhipiliopsis, was
      reinstated based on our phylogeny.

PMID- 30227215
TI  - Percutaneous Radiofrequency Ablation for Hyperhidrosis: Ready for Primetime?

PMID- 30227216
TI  - Microcoil-Guided Video-Assisted Thoracoscopic Excision of Nodules Suspicious for
      Metastasis in Patients With Extra-Thoracic Malignancies.
AB  - The purpose of this study is to determine the utility of preoperative CT-guided
      microcoil localization followed by fluoroscopy guided video-assisted
      thoracoscopic resection in the diagnosis and management of small peripheral
      pulmonary nodules in patients with extra-thoracic malignancies. This study is a
      retrospective analysis of prospectively collected data between August 2003 and
      September 2013. Fifty patients with extra-thoracic malignancies underwent
      preoperative localization of small indeterminate pulmonary nodules using CT
      guided microcoil localization. Nodules were then resected by video-assisted
      thoracoscopic resection wedge excision and intraoperative fluoroscopy guidance.
      Univariate and multivariate logistic regression analysis were conducted. Fifty
      patients with a history of 14 different extra-thoracic cancers (57% female, mean
      age 62 years) had 55 nodules resected (mean size = 12 mm, depth from visceral
      pleura = 22 mm). Histology of resected nodules showed metastasis (25 of 50
      patients), benign (10 of 50), and (15 of 50) early stage primary lung cancer.
      Smokers were found 6 times more likely to present with primary lung cancer than
      metastasis (P < 0.009). CT-guided microcoil localization procedure was successful
      in all patients with a mean time of 3110 minutes and allowed successful wedge
      resection in all cases with no major complications. The mean operative time and
      fluoroscopy time were 27(12) minutes and 3(5) minutes, respectively. Microcoil
      guided thoracoscopic wedge resection was effective in achieving early definitive
      diagnosis and changed management in 50% of patients with presumed metastasis with
      minimal morbidity.

PMID- 30227217
TI  - Characterization of PGRP-S1 from the oriental armyworm, Mythimna separata.
AB  - Peptidoglycan is the key component forming the backbone of bacterial cell wall.
      It can be recognized by a group of pattern recognition receptors, known as
      peptidoglycan recognition proteins (PGRPs) in insects and higher animals. PGRPs
      may serve as immune receptors or N-acetylmuramoyl-L-alanine amidases (EC
      3.5.1.28). Here, we report the characterization of a short PGRP, PGRP-S1, from
      the oriental armyworm, Mythimna separata. MsePGRP-S1 cDNA encodes a protein of
      197 amino acids (aa) with a PGRP domain of about 150 aa. MsePGRP-S1 was expressed
      in several tissues of naive larvae, including hemocytes, midgut, fat body and
      epidermis. Bacterial challenges caused variable changes in different tissues at
      the mRNA level. The recombinant protein bound strongly to Staphylococcus aureus
      and purified peptidoglycans from Staphylococcus aureus and Bacillus subtilis. It
      can inhibit the growth of gram-negative and gram-positive bacteria by disrupting
      bacterial surface. It can degrade peptidoglycans from Escherichia coli and
      Staphylococcus aureus. Taken together, these data demonstrate that M. separata
      PGRP-S1 is involved in defending against bacteria.

PMID- 30227218
TI  - Suppression of argonautes compromises viral infection in Penaeus monodon.
AB  - Argonaute (Ago) proteins, the catalytic component of an RNA-induced silencing
      complex (RISC) in RNA interference pathway, function in diverse processes,
      especially in antiviral defense and transposon regulation. So far, cDNAs encoding
      four members of Argonaute were found in Penaeus monodon (PmAgo1-4). Two PmAgo
      proteins, PmAgo1 and PmAgo3 shared high percentage of amino acid identity to Ago1
      and Ago2, respectively in other Penaeid shrimps. Therefore, the possible roles of
      PmAgo1 and PmAgo3 upon viral infection in shrimp were characterized in this
      study. The level of PmAgo1 mRNA expression in shrimp hemolymph was stimulated
      upon YHV challenge, but not with dsRNA administration. Interestingly, silencing
      of either PmAgo1 or PmAgo3 using sequence-specific dsRNAs impaired the efficiency
      of PmRab7-dsRNA to knockdown shrimp endogenous PmRab7 expression. Inhibition of
      yellow head virus (YHV) replication and delayed mortality rate were also observed
      in both PmAgo1-and PmAgo3-knockdown shrimp. In addition, silencing of PmAgo3
      transcript, but not PmAgo1, revealed partial inhibition of white spot syndrome
      virus (WSSV) infection and delayed mortality rate. Therefore, our study provides
      insights into PmAgo1and PmAgo3 functions that are involved in a dsRNA-mediated
      gene silencing pathway and play roles in YHV and WSSV replication in the shrimp.

PMID- 30227219
TI  - Bifidobacterium longum and VSL#3(r) amelioration of TNBS-induced colitis
      associated with reduced HMGB1 and epithelial barrier impairment.
AB  - Probiotics are a beneficial treatment for inflammatory bowel disease (IBD).
      However, studies comparing the effects of similar doses of single and mixed
      probiotics on IBD are scarce. High mobility group box 1 (HMGB1) is an important
      proinflammatory mediator involved IBD development. The present study assessed
      fecal HMGB1 levels in IBD patients and compared the effects of similar doses of
      Bifidobacterium longum (Bif) versus VSL#3(r) on HMGB1 levels in 2,4,6
      trinitrobenzene sulfonic acid (TNBS)-induced murine colitis. Twenty-four mice
      were divided into four treatment groups (n = 6 per group): ethanol (control),
      TNBS, TNBS + Bif, and TNBS + VSL#3(r). Bif and VSL#3(r) (4 * 109 CFU/dose) were
      administered daily by intragastric gavage, beginning 3 d before TNBS treatment,
      for a total of 7 d. Fecal HMGB1 levels were higher in both active IBD patients
      and TNBS-induced colitis mice versus their respective controls. Both Bif and
      VSL#3(r) improved intestinal inflammation and fecal microbiota imbalance in TNBS
      induced colitis mice. Both treatments also reduced serum and fecal HMGB1 levels
      as well as increased expression of zonula occludins-1, occludin, and claudin-1 in
      colon tissues. In Caco-2 cells, HMGB1 reduced transepithelial electrical
      resistance, zonula occludins-1 protein expression, and increased paracellular
      permeability of FITC-dextran; the opposite was found with both probiotic
      treatments. These findings suggest Bif and VSL#3(r) have similar beneficial
      effects on TNBS-induced colitis, possibly through inhibition of HMGB1 release and
      subsequent HMGB1-mediated gut barrier dysfunction. The present study provides
      novel insights into probiotic treatment of IBD.

PMID- 30227220
TI  - Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast
      cancer.
AB  - Triple-negative breast cancer (TNBC) is the most difficult subtype of breast
      cancer to treat due to a paucity of effective targeted therapies. Many studies
      have reported that breast cancer stem cells (BCSCs) are enriched in TNBC and are
      responsible for chemoresistance and metastasis. In this study, we identify LRP8
      as a novel positive regulator of BCSCs in TNBC. LRP8 is highly expressed in TNBC
      compared to other breast cancer subtypes and its genomic locus is amplified in
      24% of TNBC tumors. Knockdown of LRP8 in TNBC cell lines inhibits Wnt/beta
      catenin signaling, decreases BCSCs, and suppresses tumorigenic potential in
      xenograft models. LRP8 knockdown also induces a more differentiated, luminal
      epithelial phenotype and thus sensitizes the TNBC cells to chemotherapy.
      Together, our study highlights LRP8 as a novel therapeutic target for TNBC as
      inhibition of LRP8 can attenuate Wnt/beta-catenin signaling to suppress BCSCs.

PMID- 30227221
TI  - Cathepsin D enhances breast cancer invasion and metastasis through promoting
      hepsin ubiquitin-proteasome degradation.
AB  - Hepsin is required for the growth and maintenance of normal morphology, as well
      as for cell motility and development, initiation of blood coagulation and pro
      inflammatory immune response. Here we showed that Cathepsin D (CtsD) as a novel
      protein is involved in the regulation of hepsin. CtsD destabilizes hepsin by
      promoting its ubiquitylation and subsequent proteasomal degradation in breast
      cancer cells. Breast cancer tissue microarray also indicated that hepsin
      expression was negatively correlated with CtsD by immunohistochemistry.
      Overexpression of CtsD promoted breast cancer cell migration, invasion and
      metastasis by enhancing the expression of intercellular cell adhesion molecule-1
      (ICAM-1) in vitro and in vivo. These effects were inhibited by ectopic hepsin
      expression. Taken together, our data reveal a critical CtsD-hepsin signaling axis
      in migration and metastasis, which may contribute to a better understanding of
      the function and molecular mechanism in breast cancer progression.

PMID- 30227222
TI  - ADT with antiandrogens in prostate cancer induces adverse effect of increasing
      resistance, neuroendocrine differentiation and tumor metastasis.
AB  - Prostate cancer (PCa) is the most common cancer and the 2nd leading cause of
      cancer-related deaths among men in the United States. Androgen-deprivation
      therapy (ADT) with antiandrogens to target the androgens/androgen receptor (AR)
      signals remains the standard therapy for advanced PCa. However, most of the PCa
      patients who received ADT with antiandrogens, including the recently developed
      Enzalutamide (Enz) that might extend PCa patients survival an extra 4.8 months,
      will still develop the castration (or antiandrogen) resistance. Mechanism
      dissection studies suggest these antiandrogen resistances may involve the
      induction of AR splicing variants and/or AR mutants. Further preclinical in
      vitro/in vivo studies suggest ADT-antiandrogens may also enhance the
      neuroendocrine differentiation (NED) and PCa cell invasion, and these unwanted
      side-effects may function through various mechanisms including altering the
      infiltrating inflammatory cells within the prostate tumor microenvironment. This
      review summarizes these unwanted ADT-induced side-effects and discusses multiple
      approaches to overcome these side-effects to better suppress the PCa at the
      castration resistant stage.

PMID- 30227223
TI  - Circadian rhythms and rheumatoid arthritis.
AB  - Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of
      biological clocks located both at the level of central nervous system and inside
      peripheral cells, several daily activities, embracing sleep, feeding times,
      energy metabolism, endocrine and immune functions with related pathological
      conditions, including rheumatoid arthritis (RA). In RA the circadian rhythms
      impact on cellular functions, involving night synthesis and release of pro
      inflammatory cytokines and chemokines, cell migration to inflamed tissues,
      phagocytosis, proliferative cell response and all are peaking at late night. In
      chronic inflammatory conditions such as RA, the amplitude of the circadian rhythm
      of the anti-inflammatory endogenous cortisol availability is not increased as
      expected and requested, which indicate a reduced night cortisol secretion under
      the adrenal chronic stress induced by the disease. Therefore, the
      prevention/treatment of the immune cell night hyperactivity, with related flare
      of cytokine synthesis and morning RA clinical symptoms, has been shown more
      effective when the availability of the exogenous glucocorticoids is obtained in
      the middle of the night (night release). The impressive positive results observed
      in RA patients treated with modified-night release prednisone with a low-dose
      chronotherapy, seem applicable even for other agents such as conventional NSAIDs
      and DMARDs, including the positive experimental and clinical results obtained by
      the night time daily administration of methotrexate. Interestingly, a very recent
      study showed that methotrexate upregulates important cell circadian genes,
      resulting in induction of apoptosis in synovial fibroblasts. The link between the
      circadian rhythms of the disease and the chronotherapy of RA is promising.

PMID- 30227224
TI  - CONTRIBUTIONS OF NOCIRESPONSIVE AREA 3A TO NORMAL AND ABNORMAL SOMATOSENSORY
      PERCEPTION.
AB  - : Traditionally, cytoarchitectonic area 3a of primary somatosensory cortex (SI)
      has been regarded as a proprioreceptive relay to motor cortex. However, neuronal
      spike train recordings and optical intrinsic signal imaging, obtained from
      nonhuman sensorimotor cortex, show that neuronal activity in some of cortical
      columns in area 3a can be readily triggered by C-nociceptor afferent drive. These
      findings indicate that area 3a is a critical link in cerebral cortical encoding
      of 2nd/slow pain. Also, area 3a contributes to abnormal pain processing in the
      presence of activity-dependent reversal of GABAA receptor-mediated inhibition.
      Accordingly, abnormal processing within area 3a may contribute mechanistically to
      generation of clinical pain conditions. PERSPECTIVE: Optical imaging and
      neurophysiological mapping of area 3a of primary somatosensory cortex (SI) has
      revealed substantial driving from unmyelinated cutaneous nociceptors,
      complementing input to areas 3b and 1 of SI from myelinated nociceptors and non
      nociceptors. These and related findings force a reconsideration of mechanisms for
      SI processing of pain.

PMID- 30227225
TI  - Differential anti-microbial secondary metabolites in different ESKAPE pathogens
      explain their adaptation in the hospital setup.
AB  - Nosocomial infections are caused by ESKAPE (E. faecium, S. aureus, K. pneumoniae,
      A. baumannii, P. aeruginosa, and E. cloacae) pathogens, and their co-existence is
      associated with their ability to survive in the hospital setup. They may produce
      molecules, which helps in the better survival of one ESKAPE pathogens over other.
      We have identified all secondary metabolite gene clusters in six ESKAPE pathogens
      and predicted antimicrobial and anti-biofilm properties of their product
      secondary metabolites. To validate our model, we have taken the secondary
      metabolites of ESKAPE pathogens and studied their interaction with diguanylate
      cyclase (involved in quorum sensing) and biofilm-associated protein (involved in
      biofilm formation) of Acinetobacter baumannii. Results suggest the presence of
      differential secondary metabolites in all ESKAPE pathogens with only three common
      non-antimicrobial secondary metabolites. Out of twenty-three antimicrobial
      secondary metabolites, TP-1161, nosiheptide and meilingmycin, showed the best
      antimicrobial activity and nineteen showed high anti-biofilm activity.
      Interaction study showed that secondary metabolites produced by other ESKAPE
      pathogens (non-Acinetobacter) have very good interaction with diguanylate cyclase
      and biofilm-associated protein of A. baumannii. This concludes that better
      survival of these ESKAPE pathogens in hospital setup can be correlated with
      differential production of antimicrobial secondary metabolites. The present study
      also investigates the molecular mechanism of the competition of different
      pathogens living in similar hospital setup (similar habitat). Therefore, the
      present study will initiate research that might lead to the discovery of
      antibiotics from one ESKAPE pathogen that controls the infection of other ESKAPE
      pathogens or other pathogens.

PMID- 30227226
TI  - International high-risk clonal lineages of CTX-M-producing Escherichia coli F
      ST648 in free-roaming cats, South America.
AB  - The dissemination of extended-spectrum beta-lactamase (ESBL)-producing
      Escherichia coli belonging to high-virulent pandemic lineages has become a global
      problem with serious consequences for public health worldwide. In this regard, E.
      coli lineages belonging to the sequence type ST648, which are mostly associated
      with human infections, have begun to be reported in animals. In this study, we
      report the identification and genomic characterization of international CTX-M
      producing E. coli ST648/F lineages in free-roaming cats from an urban slum, in
      Brazil. Moreover, we have performed a comparative genomic analysis of worldwide
      reported E. coli ST648 strains, highlighting an epidemiologic linkage between
      human and companion animals.

PMID- 30227228
TI  - In vitro interaction of Candida tropicalis biofilm formed on catheter with human
      cells.
AB  - Candida tropicalis has emerged as one of the major Candida non-C. albicans
      species, in terms of epidemiology and virulence. Despite its virulence, C.
      tropicalis pathogenic mechanism has yet not been fully defined. The current study
      aimed to demonstrate the interaction of mature C. tropicalis ATCC 750 biofilm
      formed on catheter with different human cell lines. In vitro mature (72 h) C.
      tropicalis biofilms were produced on small catheter fragments (SCF) and were
      mainly composed by blastoconidia. Then, migration of yeast cells from mature
      biofilm to human cell surfaces (HeLa and HUVEC) was investigated. After contact
      with both cell lines, the surface of SCF, containing mature C. tropicalis
      biofilm, exhibited predominantly the filamentous form. Meanwhile, fresh biofilm
      formed on human cell surfaces also revealed mainly of blastoconidia involved by
      extracellular matrix. Total biomass and metabolic activity from the remaining
      biofilm on SCF surface, after direct contact with human cells, exhibited a
      significant reduction. Mature C. tropicalis biofilm modified its extracellular
      matrix components, after contact with human cells. Thus, we described for the
      first time an easy and simple in vitro model with catheter, which could be a
      powerful tool for future studies that desires to elucidate the mechanisms
      involved in C. tropicalis biofilm.

PMID- 30227227
TI  - The characteristics of pallidal low-frequency and beta bursts could help
      implementing adaptive brain stimulation in the parkinsonian and dystonic internal
      globus pallidus.
AB  - INTRODUCTION: Adaptive deep brain stimulation (aDBS) has been applied in
      Parkinson's disease (PD), based on the presence of brief high-amplitude beta (13
      35 Hz) oscillation bursts in the subthalamic nucleus (STN), which correlate with
      symptom severity. Analogously, average low-frequency (LF) oscillatory power (4-12
      Hz) in the internal globus pallidus (GPi) correlates with dystonic symptoms and
      might be a suitable physiomarker for aDBS in dystonia. Characterization of
      pallidal bursts could facilitate the implementation of aDBS in the GPi of PD and
      dystonia patients. OBJECTIVE AND METHODS: We aimed to describe the bursting
      behaviour of LF and beta oscillations in a cohort of five GPi-DBS PD patients and
      compare their amplitude and length with those of a cohort of seven GPi-DBS
      dystonia, and six STN-DBS PD patients (n electrodes = 34). Furthermore, we used
      the information obtained to set up aDBS and test it in the GPi of both a dystonia
      and a PD patient (n = 2), using either LF (dystonia) or beta oscillations (PD) as
      feedback signals. RESULTS: LF and beta oscillations in the dystonic and
      parkinsonian GPi occur as phasic, short-lived bursts, similarly to the
      parkinsonian STN. The amplitude profile of such bursts, however, differed
      significantly. Dystonia showed higher LF burst amplitudes, while PD presented
      higher beta burst amplitudes. Burst characteristics in the parkinsonian GPi and
      STN were similar. Furthermore, aDBS applied in the GPi was feasible and well
      tolerated in both diseases. CONCLUSION: Pallidal LF and beta burst amplitudes
      have different characteristics in PD and dystonia. The presence of increased
      burst amplitudes could be employed as feedback for GPi-aDBS.

PMID- 30227229
TI  - Pathogenicity-island-encoded regulatory RNAs regulate bacterial virulence and
      pathogenesis.
AB  - Bacterial regulatory RNAs (regRNAs) have been widely studied for decades and
      shown to be involved in various aspects of bacterial survival, including their
      virulence and pathogenesis. Recently, many regRNAs have been found to be encoded
      within bacterial pathogenicity islands (PAIs). These PAI-encoded regRNAs also
      play important regulatory roles in bacterial virulence and pathogenesis. In this
      review, we introduce the reported PAI-encoded regRNAs individually, focusing on
      their types, target genes, regulatory roles, regulatory mechanisms and
      significance. We also summarize the virulence and pathogenesis of the pathogens
      concerned.

PMID- 30227230
TI  - Polymicrobial antibiofilm activity of the membranotropic peptide gH625 and its
      analogue.
AB  - This work illustrates a new role for the membranotropic peptide gH625 and its
      derivative gH625-GCGKKK in impairing formation of polymicrobial biofilms. Mixed
      biofilms composed of Candida and bacterial species cause frequently infections
      and failure of medical silicone devices and also show a major drug resistance
      than single-species biofilms. Inhibition and eradication of biofilms were
      evaluated by complementary methods: XTT-reduction, and crystal violet staining
      (CV). Our results indicate that gH625-GCGKKKK, better than the native peptide,
      strongly inhibited formation of mixed biofilms of clinical isolates of C.
      tropicalis/S. marcescens and C. tropicalis/S. aureus and reduced the biofilm
      architecture, interfering with cell adhesion and polymeric matrix, as well as
      eradicated the long-term polymicrobial biofilms on silicone surface.

PMID- 30227231
TI  - The error-related negativity for error processing in interoception.
AB  - The error-related negativity (ERN) is an event-related potential in the
      electroencephalogram (EEG) observed within the first 100 ms after commission of
      an error. Increased ERN amplitudes have been observed in several psychological
      disorders characterized by high negative affect. While the ERN has extensively
      been studied in tasks using exteroceptive stimuli, its relation to interoceptive
      stimuli is unknown. Since errors related to interoception might be particularly
      relevant for survival and negative affect, this study aimed to explore the ERN
      for errors related to interoceptive, respiratory sensations (intERN). Moreover,
      we compared the intERN with a commonly observed ERN related to exteroceptive,
      visual stimuli (extERN) and examined their associations with interoception
      related negative affect. We studied the ERN using a respiratory occlusion task
      (intERN) and a visual flanker task (extERN) in 40 healthy volunteers during
      continuous 129 channel EEG recordings. In the occlusion task, participants
      received inspiratory occlusions of two different durations and indicated whether
      each occlusion was short or long. In the Flanker task, participants indicated the
      direction of arrowheads. Interoception-related negative affect was assessed with
      the Anxiety Sensitivity Index. Comparable with the extERN, the intERN was
      observed at fronto-central scalp positions after error commission in the
      occlusion task, but it peaked significantly earlier than the extERN. Mean
      amplitudes of the intERN and extERN showed no significant difference and were not
      correlated. Moreover, higher levels of anxiety sensitivity were correlated with
      significantly greater amplitudes of the intERN, but with lower amplitudes of the
      extERN. The present results firstly demonstrate an error-related negativity EEG
      potential that is related to interoceptive sensations (intERN). This intERN is
      not associated with a commonly observed ERN elicited by exteroceptive stimuli and
      is distinctly linked to higher levels of interoception-related negative affect.
      The intERN might be a promising neural marker for future studies on
      interoception, negative affect and error processing.

PMID- 30227232
TI  - Outcomes of Patients with Recurrent and Refractory Lymphoma Undergoing Allogeneic
      Hematopoietic Cell Transplantation with BEAM Conditioning and Sirolimus- and
      Tacrolimus-Based GVHD Prophylaxis.
AB  - The current standard of care for patients with Hodgkin lymphoma (HL) and non
      Hodgkin lymphoma (NHL) is high-dose conditioning followed by autologous stem cell
      transplantation (ASCT). For some patients (ie, those with highest-risk disease,
      insufficient stem cell numbers after mobilization, or bone marrow involvement)
      allogeneic hematopoietic cell transplantation (alloHCT) offers the potential for
      cure. However, the majority of patients undergoing alloHCT receive reduced
      intensity conditioning as a preparative regimen, and studies assessing outcomes
      of patients after alloHCT with myeloablative conditioning are limited. In this
      retrospective study, we reviewed outcomes of 22 patients with recurrent and
      refractory NHL who underwent alloHCT with myeloablative BEAM conditioning and
      received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis at
      City of Hope between 2005 and 2018. With a median follow-up of 2.6 years (range,
      1.0 to 11.2 years), the probabilities of 2-year overall survival and event-free
      survival were 58.3% (95% confidence interval [CI], 35.0% to 75.8%) and 45.5% (95%
      CI, 24.4% to 64.3%), respectively. The cumulative incidence of grade II to IV
      acute GVHD was 45.5% (95% CI, 23.8% to 64.9%), with only 1 patient developing
      grade IV acute GVHD. However, chronic GVHD was seen in 55% of the patients (n =
      12). Of the 22 eligible patients, 2 had undergone previous ASCT and 2 had
      undergone previous alloHCT. Both patients with previous ASCT developed severe
      regimen-related toxicity. Patients who underwent alloHCT with chemorefractory
      disease had lower survival rates, with 1-year OS and EFS of 44.4% and 33.0%,
      respectively. In conclusion, alloHCT with a BEAM preparative regimen and
      tacrolimus/sirolimus-based GVHD should be considered as an alternative option for
      patients with highest-risk lymphoma whose outcomes are expectedly poor after
      ASCT.

PMID- 30227233
TI  - Estrogen in vascular smooth muscle cells: A friend or a foe?
AB  - Cardiovascular disease (CVD) continues to be the leading cause of death
      worldwide. The effect of estrogen on these diseases has been assessed in in vitro
      and in vivo models, as well as in observational studies. Collectively, these
      studies alluded to a cardiovasculo-protective effect of estrogen. However,
      comprehensive clinical investigation failed to produce concrete proof of a
      cardiovascular protective effect for hormone replacement therapy (HRT), let alone
      rule out potential harm. These seemingly paradoxical effects of estrogen were
      explained by the 'theory of timing and opportunity'. This theory states that the
      effect of estrogen, whether cardiovasculo-protective or pathological,
      significantly depends on the age of the individual when estrogen administration
      takes place. Here, we review the conflicting effects of estrogen on vascular
      smooth muscle cells, mainly proliferation and migration as two cellular
      capacities intimately related to physiology and pathophysiology of the
      cardiovascular system. Furthermore, we critically discuss the major parameters
      and signaling pathways that may account for the aforementioned paradoxical
      observations, as well as the key molecular players involved.

PMID- 30227234
TI  - Increase of histone acetylation in the GABAergic neurons in the rostral
      ventromedial medulla associated with mechanical hypersensitivity after repeated
      restraint stress.
AB  - Psychophysical stresses frequently increase sensitivity and response to pain,
      which is termed stress-induced hyperalgesia (SIH). However, the mechanism remains
      unknown. The rostral ventromedial medulla (RVM) and locus coeruleus (LC) are core
      elements of the descending pain modulatory system, which modulate nociceptive
      transmission in the spinal dorsal horn. In the present study we examined the
      acetylation of histone H3 in the RVM and LC after repeated restraint stress for 3
      weeks to clarify changes in the descending pain modulatory system in the rat with
      SIH. The repeated restraint stress induced mechanical hypersensitivity in the
      hindpaw and an increase in acetylation of histone H3 in the RVM but not the LC.
      The number of acetylated histone H3-IR cells in the RVM was significantly higher
      in the repeated restraint group (282.9 +/- 43.1) than that in the control group
      (134.7 +/- 15.6, p <  0.05). Furthermore, the repeated restraint stress increased
      acetylation of histone H3 in the RVM GABAergic neurons but not the RVM
      serotonergic neurons. The GAD67 protein level in the RVM was significantly higher
      in repeated restraint group (144.9 +/- 17.0%) than that in the control group
      (100.0 +/- 8.9%, p < 0.05). These findings suggest the possibility that the
      stress-induced neuroplasticity in the RVM GABAergic neurons is involved in the
      mechanical hypersensitivity due to the dysfunction of the descending pain
      modulatory system.

PMID- 30227235
TI  - Chronic asthma-induced behavioral and hippocampal neuronal morphological changes
      are concurrent with BDNF, cofilin1 and Cdc42/RhoA alterations in immature mice.
AB  - INTRODUCTION: Recent studies have found that persistent hypoxia caused by chronic
      asthma, especially during childhood, affects the development and function of the
      brain, but the mechanism is unclear. In the present study, BDNF and its signal
      pathway was investigated in mediating chronic asthma induced-neuronal changes
      that lead to behavior alterations. METHODS: The chronic asthma model was induced
      by sensitization with ovalbumin for more than 9 weeks in immature mice. Morris
      water maze test (MWMT), open field test (OFT) and elevated plus maze test (EPMT)
      were used to conduct behavioral evaluation. Neuronal morphology in hippocampal
      CA1, CA3 and DG was assessed using ImageJ's Sholl plugin and RESCONSTRUCT
      software. BDNF signaling pathway related molecules was determined by Western
      blotting. RESULTS: Chronic asthma does affect the behavioral performances of
      immature mice evaluated in MWMT, OFT, and EPMT. The analysis by three-dimensional
      reconstruction software found that following the behavioral alteration of
      asthmatic mice, dendritic changes also occurred in hippocampal neurons, including
      shortened dendrite length, significantly reduced number of dendritic branches,
      decreased density of dendritic spines, and reduced percentage of functional
      dendritic spine types. At the same time, by immunofluorescence and western
      blotting, we also found that alterations in dendritic morphology were consistent
      with activation of cofilin1 and changes in BDNF-Cdc42/RhoA levels. Some of the
      changes mentioned above can be alleviated by intranasal administration of
      budesonide. CONCLUSION: Our data suggest that response similar to nicotine
      withdrawal or/and hypoxia induced by childhood chronic asthma enhances the BDNF
      Cdc42/RhoA signaling pathway and activates cofilin1, leading to the remodeling of
      actin, causing the loss of dendritic spines and atrophy of dendrites, eventually
      resulting in behavioral alterations.

PMID- 30227236
TI  - Amyloidogenesis induced by diet cholesterol and copper in a model mouse for
      Alzheimer's disease and protection effects of zinc and fluvastatin.
AB  - Alzheimer's disease (AD) is one of the severe chronic diseases characterized with
      amyloid beta (Abeta) aggregation and formation of senile-plaque (SP) like
      structures. Numerous risk factors including trace metals and cholesterol in diet
      have been identified as potential players for the onset of Abeta aggregation. To
      further illustrate the effects of copper and cholesterol in AD pathology, we
      employed an AD model mouse strain (Tg2567) and examined the histological and
      biochemical changes in the mouse brains and blood. When supplied with 0.1 mg/L
      copper in drinking water and 2% cholesterol in the food, the mice showed
      significant deposit of amyloid beta (Abeta) and SP plaque formation in
      hippocampus and temporal cortex regions in their brains. These mice also showed
      elevated superoxide dismutase (SOD) activity and increased ceruloplasmin (CP)
      concentration, and reduced glutathione peroxidase (Gpx) activity in the blood.
      The physiological function tests indicated these mice were significantly impeded
      on learning and memory. We further examined the counteracting effects of 0.1 mg/L
      zinc and 1.0 mg/L fluvastatin (Cholesterol-lowering drug). The combination of
      zinc and fluvastatin effectively reversed the copper/cholesterol caused memory
      loss, anatomic amyloid deposits and the biochemical changes in the blood. This
      work provides more evidence of high-level cholesterol and copper as risk factors
      to trigger amyloid aggregation and mental dementia; zinc and reduction of food
      cholesterol levels can protect the animals from amyloid accumulation and learning
      impairment. The beneficial outcomes of zinc and fluvastatin could hint some
      potential usages in preventive measures for high-risk AD individuals, but further
      rigorous test are needed.

PMID- 30227237
TI  - TGFbeta, smooth muscle cells and coronary artery disease: a review.
AB  - Excessive vascular smooth muscle cell (SMC) proliferation, migration and
      extracellular matrix (ECM) synthesis are key events in the development of intimal
      hyperplasia, a pathophysiological response to acute or chronic sources of
      vascular damage that can lead to occlusive narrowing of the vessel lumen.
      Atherosclerosis, the primary cause of coronary artery disease, is characterised
      by chronic vascular inflammation and dyslipidemia, while revascularisation
      surgeries such as coronary stenting and bypass grafting represent acute forms of
      vascular injury. Gene knockouts of transforming growth factor-beta (TGFbeta), its
      receptors and downstream signalling proteins have demonstrated the importance of
      this pleiotropic cytokine during vasculogenesis and in the maintenance of
      vascular homeostasis. Dysregulated TGFbeta signalling is a hallmark of many
      vascular diseases, and has been associated with the induction of pathological
      vascular cell phenotypes, fibrosis and ECM remodelling. Here we present an
      overview of TGFbeta signalling in SMCs, highlighting the ways in which this
      multifaceted cytokine regulates SMC behaviour and phenotype in cardiovascular
      diseases driven by intimal hyperplasia.

PMID- 30227238
TI  - Tobacco smoke and nicotine suppress expression of activating signaling molecules
      in human dendritic cells.
AB  - Cigarette smoke has significant toxic effects on the immune system, and increases
      the risk of developing autoimmune diseases; one immunosuppressive effect of
      cigarette smoke is that it inhibits the T cell-stimulating, immunogenic
      properties of myeloid dendritic cells (DCs). As the functions of DCs are
      regulated by intra-cellular signaling pathways, we investigated the effects of
      cigarette smoke extract (CSE) and nicotine on multiple signaling molecules and
      other regulatory proteins in human DCs to elucidate the molecular basis of the
      inhibition of DC maturation and function by CSE and nicotine. Maturation of
      monocyte-derived DCs was induced with the TLR3-agonist poly I:C or with the TLR4
      agonist lipopolysaccharide, in the absence or presence of CSE or nicotine.
      Reverse-phase protein microarray was used to quantify multiple signaling
      molecules and other proteins in cell lysates. Particularly in poly I:C-matured
      DCs, cigarette smoke constituents and nicotine suppressed the expression of
      signaling molecules associated with DC maturation and T cell stimulation, cell
      survival and cell migration. In conclusion, constituents of tobacco smoke
      suppress the immunogenic potential of DCs at the signaling pathway level.

PMID- 30227239
TI  - Comparison of multi-linear regression, particle swarm optimization artificial
      neural networks and genetic programming in the development of mini-tablets.
AB  - In the present study, the preparation of pharmaceutical mini-tablets was
      attempted in the framework of Quality by Design (QbD) context, by comparing
      traditionally used multi-linear regression (MLR), with artificially-intelligence
      based regression techniques (such as standard artificial neural networks (ANNs),
      particle swarm optimization (PSO) ANNs and genetic programming (GP)) during
      Design of Experiment (DoE) implementation. Specifically, the effect of diluent
      type and particle size fraction for three commonly used direct compression
      diluents (lactose, pregelatinized starch and dibasic calcium phosphate dihydrate,
      DCPD) blended with either hydrophilic or hydrophobic flowing aids was evaluated
      in terms of: a) powder blend properties (such as bulk (Y1) and tapped (Y2)
      density, Carr's compressibility index (Y3, CCI), Kawakita's compaction fitting
      parameters a (Y4) and 1/b (Y5)), and b) mini-tablet's properties (such as
      relative density (Y6), average weight (Y7) and weight variation (Y8)). Results
      showed better flowing properties for pregelatinized starch and improved packing
      properties for lactose and DPCD. MLR analysis showed high goodness of fit for the
      Y1, Y2, Y4, Y6 and Y8 with RMSE values of Y1 = 0.028, Y2 = 0.032, Y4 = 0.019, Y6
      = 0.015 and Y8 = 0.130; while for rest responses, high correlation was observed
      from both standard ANNs and GP. PSO-ANNs fitting was the only regression
      technique that was able to adequately fit all responses simultaneously (RMSE
      values of Y1 = 0.026, Y2 = 0.022, Y3 = 0.025, Y4 = 0.010, Y5 = 0.063, Y6 = 0.013,
      Y7 = 0.064 and Y8 = 0.104).

PMID- 30227240
TI  - Inhalation treatment of idiopathic pulmonary fibrosis with curcumin large porous
      microparticles.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease
      with high mortality and poor prognosis. Curcumin shows anti-inflammatory effect
      by suppressing pro-inflammatory cytokines and inhibiting NF-kappaB mediated
      inflammation. Here, we developed inhalable curcumin-loaded poly(lactic-co
      glycolic)acid (PLGA) large porous microparticles (LPMPs) for the treatment of
      IPF. Curcumin LPMPs were rough and loose particles with many pores on the
      surfaces and channels in the inner spaces. The mean geometric diameter of them
      was larger than 10 um while the aerodynamic diameter was only 3.12 um due to
      their porous structures. They showed a fine particle fraction (FPF) <4.46 MUm of
      13.41%, 71% cumulative release after 9 h, and more importantly, they avoided
      uptake by alveolar macrophages. Therefore, most of released curcumin had
      opportunities to enter lung tissues. Rat pulmonary fibrosis models were
      established via once intratracheal administration of bleomycin. Curcumin powders
      and curcumin LPMPs were administered on Days 2, 7, 14, and 21. Curcumin LPMPs
      remarkably attenuated lung injuries, decreased hydroxyproline contents, reduced
      the synthesis of collagen I, and inhibited the expressions of TNF-alpha, TGF
      beta1, NF-kappaB p65 and MMP9. Moreover, curcumin LPMPs showed higher
      antifibrotic activity than curcumin powders. Curcumin LPMPs are a promising
      inhalable medication for the treatment of IPF.

PMID- 30227241
TI  - Drug development and therapeutic solutions in the digital age.

PMID- 30227242
TI  - Estrogen and progesterone dependent expression of visfatin/NAMPT regulates
      proliferation and apoptosis in mice uterus during estrous cycle.
AB  - Visfatin is an adipokine which has an endocrine effect on reproductive functions
      and regulates ovarian steroidogenesis. There is scant information about the
      expression, regulation, and functions of visfatin in the mammalian uterus. The
      present study examined expression and localization of visfatin in the mouse
      uterus at various stages of the natural estrous cycle, effects of estrogen and
      progesterone on localization and expression of visfatin in the ovariectomised
      mouse uterus and effect of visfatin inhibition by a specific inhibitor, FK866 on
      proliferation and apoptosis in the uterus. Western blot analysis of visfatin
      showed high expression in proestrus and metestrus while it declined in estrus and
      diestrus. Immulocalization study also showed strong immunostaining in the cells
      of endometrium, myometrium, luminal and glandular epithelium during proestrus and
      metestrus that estrus and diestrus. The uterine visfatin expression closely
      related to the increased estrogen levels in proestrus and suppressed when
      progesterone rose to a high level in diestrus. The treatment with estrogen to
      ovariectomised mice up-regulates visfatin, PCNA, and active caspase3 whereas
      progesterone up-regulates PCNA and down-regulates visfatin and active caspase3
      expression in mouse uterus. The co-treatment with estrogen and progesterone up
      regulates visfatin and down-regulates PCNA and active caspase3. In vitro study
      showed endogenous visfatin inhibition by FK866 increased expression of PCNA and
      BCL2 increased catalase activity while FK866 treatment decreased expression of
      active caspase3 and BAX with decreased SOD and GPx activity. BrdU labeling showed
      that inhibition of visfatin modulates the uterine proliferation. This study
      showed that expression of visfatin protein is steroid dependent in mouse uterus
      which is involved in the regulation of proliferation and apoptosis via modulating
      antioxidant system in the uterus of mice during the reproductive cycle.

PMID- 30227243
TI  - The dual sex hormone specificity for human reductive 17beta-hydroxysteroid
      dehydrogenase type 7: Synergistic function in estrogen and androgen control.
AB  - Human 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1 and 7 catalyze the
      final step of estrogen activation and the first step in androgen inactivation. It
      has been shown in breast cancer cells that DHT has a suppression effect on cell
      proliferation, counteracting the estrogen growth effect. However, the exact
      kinetic function of 17beta-HSD7 in steroidogenesis was not determined. Here we
      report the steady-state kinetics and binding study for 17beta-HSD7 with estrone
      or DHT as substrates and NADPH as cofactor. 17beta-HSD7 has been overexpressed in
      E. coli and purified. For both substrates, kinetics of 17beta-HSD7 demonstrates
      positive cooperativity. The K0.5 value is 5.2 +/- 0.4 MUM and 14.4 +/- 0.8 MUM
      and the kcat is 0.0063 +/- 0.0003 s-1 and 0.0153 +/- 0.0007 s-1 for the reduction
      of E1 and DHT, respectively. The binding study shows a similar affinity with a
      dissociation constant of 5.2 +/- 0.5 MUM and 11 +/- 1 MUM for E1 and DHT,
      respectively. Our kinetic and binding results reveal a positive cooperativity for
      17beta-HSD7 to both the E1 and DHT with a similar affinity, while 17beta-HSD1
      demonstrated a significantly higher affinity toward E1 than DHT, but with a
      strong E1 substrate inhibition. These results strongly support that the
      inhibition of 17beta-HSD7 constitutes the basis of breast cancer cell
      proliferation decreasing that led to the shrinkage of xenograft ER + breast tumor
      mice model.

PMID- 30227245
TI  - Short prism adaptation test in patients with acquired nonaccommodative esotropia;
      clinical findings and surgical outcome.
AB  - PURPOSE: To evaluate the surgical outcomes in patients with acquired
      nonaccommodative esotropia operated on based on a short prism adaptation test
      (PAT) and to determine the subgroup of patients most responsive to PAT. METHODS:
      In this prospective interventional cases series, patients with acquired
      nonaccommodative esotropia were enrolled. Patients wore Fresnel trial lenses
      based on the results of alternate prism-cover testing. With the Fresnel prism in
      place, alignment was measured after 20 minutes. If deviation increased, the power
      of prism was increased to neutralize this angle. The test was repeated every 20
      minutes to achieve motor stability. Patients were classified as either prism
      responders (if the angle of deviation increased >10Delta compared to the entry
      angle) or prism nonresponders. All patients underwent bilateral medial rectus
      muscle recession. Prism responders underwent surgical correction based on the
      enhanced angle. RESULTS: Of the 28 subjects enrolled, 14 (50%) were prism
      responders and 14 (50%) were classified as prism nonresponders. After 6 months,
      100% of prism responders and 92.9% of nonresponders were aligned within 8Delta of
      orthotropia at distance and near fixation. None of the patients with an entry
      angle of >30Delta were prism responders. CONCLUSIONS: In our study cohort, a
      short PAT with an endpoint of motor stability in patients with acquired
      nonaccommodative esotropia was associated with a good surgical outcome and a low
      rate of over- and undercorrection. PAT may be unnecessary for patients with an
      angle of deviation of >30Delta.

PMID- 30227244
TI  - Failure of intravenous artesunate treatment for Plasmodium falciparum malaria in
      a splenectomized traveller: A diagnostic challenge.

PMID- 30227246
TI  - Implementing enhanced education to improve the UCLA Preschool Vision Program.
AB  - PURPOSE: To examine whether educational pamphlets and videos for adults can
      increase follow-up rates for eye examinations among preschool children. METHODS:
      The target population was 3- to 5-year-olds attending preschools within Los
      Angeles County and receiving services from the UCLA Preschool Vision Program
      (UPVP). Preschools were randomly assigned to standard and enhanced-education
      groups. The same procedures were followed in each group, except that preschool
      personnel and parents of children referred for eye examinations in the enhanced
      education group received education materials and watched a 3-minute informational
      video on the screening day. The outcome measure was the follow-up rate for
      comprehensive examinations performed by the UPVP on a second date. RESULTS: The
      follow-up rate for receiving a complete eye examination was 75.3% (438/582) in
      the enhanced-education group and 65.1% (430/661) in the standard group (P <
      0.0001 [Fisher exact test]; OR = 1.63; 95% CI, 1.28-2.09). CONCLUSIONS: Educating
      adults during the screening session can increase follow-up rates. Further studies
      are recommended to understand barriers to seeking eye care for children and to
      devise initiatives to help increase targeted awareness.

PMID- 30227247
TI  - Congenital dacryocystocele: sonographic evaluation of 11 cases.
AB  - PURPOSE: To report prenatal sonographic findings of congenital dacryocystocele.
      METHODS: The medical records of all cases diagnosed with congenital
      dacryocystocele at a tertiary care center from 2003 to 2015 were reviewed
      retrospectively. RESULTS: Eleven cases of congenital dacryocystocele were
      analyzed. No accompanying fetal anatomic anomalies where detected. Mean maternal
      age at evaluation was 22 years of age (range, 17-32 years). Four of 10 cases were
      primigravidas. The mean gestational age at evaluation was 32.6 weeks' gestational
      age. Ten out of 11 cases occurred in female fetuses (91%). Of the 11, 10 cases
      were unilateral and 1 was bilateral. The mean diameter at evaluation was 5.1 mm.
      Spontaneous resolution occurred in 2 cases (18%). In the remaining 9 fetuses,
      postnatal diagnosis of dacryocystocele were confirmed by an ophthalmologist
      evaluation. CONCLUSIONS: Prenatally diagnosed congenital dacryocystocele may
      undergo spontaneous resolution before birth. However, a better understanding of
      the prenatal sonographic findings can help to appropriately orient parents of
      potentially affected fetuses. Referral to a pediatrician and pediatric
      ophthalmologist may be considered for complete evaluation and postnatal
      management.

PMID- 30227248
TI  - Modified anterior transposition of the inferior oblique muscle.
AB  - PURPOSE: To introduce a modified method of anterior transposition of inferior
      oblique (ATIO) and compare with traditional method in terms of efficacy and
      complications. METHODS: The medical records of patients who had undergone
      unilateral ATIO and were followed for at least 6 months were reviewed
      retrospectively. The patients were divided into two groups according to the
      surgical method: modified ATIO (modified group, n = 16) and traditional ATIO
      (traditional group, n = 15). In modified ATIO, the anterior nasal fibers of the
      inferior oblique muscle were anchored to the sclera and the posterior temporal
      fibers were folded and buried under the fixed anterior nasal fiber of inferior
      oblique muscle. In the traditional method, both the anterior and posterior fibers
      were fixed with individual suturing. Postoperative change in vertical deviation
      and grade of inferior oblique overaction (IOOA) were analyzed. Complications,
      including antielevation syndrome, fat adherence syndrome, and lower lid deformity
      were assessed. RESULTS: Both modified and traditional methods effectively
      weakened the action of the inferior oblique muscle. The efficacy of the two
      methods did not differ in terms of change in vertical deviation (P = 0.225) and
      grade of IOOA (P = 0.169). Antielevation syndrome occurred more frequently in the
      traditional group than in the modified group (8/15 vs 2/16, resp. [P = 0.019]).
      Incidences of fat adherence syndrome (0/15 vs 0/16 [P = 1.0]) and lid deformity
      (3/15 vs 1/15 [P = 0.678]) were not different. CONCLUSIONS: Modified ATIO was
      comparable to traditional ATIO in correcting vertical deviation and IOOA and had
      a lower risk of antielevation syndrome compared with traditional ATIO.

PMID- 30227249
TI  - Angiotensin II upregulates CYP4A isoform expression in the rat kidney through
      angiotensin II type 1 receptor.
AB  - Angiotensin II (AngII) stimulates the renal production and release of 20
      hydroxyeicosatetraenoic acids (20-HETE), which is a major metabolite of
      arachidonic acid catalyzed by CYP4A isoforms. However, the effects of AngII on
      CYP4A isoform expression in the kidney and its mechanism remains unclear. To
      clarify the regulation of CYP4A isoform expression by AngII, we examined the
      chronic effects of AngII and AngII type 1 receptor (AT1-R) blockade on CYP4A
      isoform expression. Sprague-Dawley rats were infused with vehicle or AngII for 1
      week, and the AngII-infused rats were also treated with or without the AT1-R
      blocker, candesartan. AngII increased CYP4A isoform protein expression in the
      renal cortex (CO) and outer medulla (OM) in a dose-dependent manner, and
      candesartan inhibited the AngII-increased CYP4A expression in a dose-dependent
      manner. AngII increased the CYP4A isoform mRNA expression in the CO and OM, and
      candesartan inhibited AngII-increased CYP4A isoform mRNA expression. These
      results indicated that AngII chronically increased the CYP4A isoform expression
      in the rat kidney. The AngII-induced CYP4A isoform expression was mediated by AT1
      R.

PMID- 30227251
TI  - Application of a curated genome-scale metabolic model of CHO DG44 to an
      industrial fed-batch process.
AB  - CHO cells have become the favorite expression system for large scale production
      of complex biopharmaceuticals. However, industrial strategies for upstream
      process development are based on empirical results, due to a lack of fundamental
      understanding of intracellular activities. Genome scale models of CHO cells have
      been reconstructed to provide an economical way of analyzing and interpreting
      large-omics datasets, since they add cellular context to the data. Here the most
      recently available CHO-DG44 genome-scale specific model was manually curated and
      tailored to the metabolic profile of cell lines used for industrial protein
      production, by modifying 601 reactions. Generic changes were applied to simplify
      the model and cope with missing constraints related to regulatory effects as well
      as thermodynamic and osmotic forces. Cell line specific changes were related to
      the metabolism of high-yielding production cell lines. The model was semi
      constrained with 24 metabolites measured on a daily basis in n = 4 independent
      industrial 2L fed batch cell culture processes for a therapeutic antibody
      production. This study is the first adaptation of a genome scale model for CHO
      cells to an industrial process, that successfully predicted cell phenotype. The
      tailored model predicted accurately both the exometabolomics data (r2 >= 0.8 for
      96% of the considered metabolites) and growth rate (r2 = 0.91) of the industrial
      cell line. Flux distributions at different days of the process were analyzed for
      validation and suggestion of strategies for medium optimization. This study shows
      how to adapt a genome scale model to an industrial process and sheds light on the
      metabolic specificities of a high production process. The curated genome scale
      model is a great tool to gain insights into intracellular fluxes and to identify
      possible bottlenecks impacting cell performances during production process. The
      general use of genome scale models for modeling industrial recombinant cell lines
      is a long-term investment that will highly benefit process development and speed
      up time to market.

PMID- 30227250
TI  - Prognostic value of circulating cell-free DNA in patients with pancreatic cancer:
      A systemic review and meta-analysis.
AB  - Because of the deep research about tumorigenesis mechanism, the cognition of
      cancer has been transferred to molecular level from morphology. Previous articles
      reported a potential connection between circulating cell-free DNA (cfDNA) and
      prognosis of pancreatic cancer. A total of 18 related articles including 1243
      patients were enrolled to access the relationship between cfDNA and prognosis of
      pancreatic cancer. The hazard ratio (HR) was used to combine the univariate and
      multivariate results of included studies. Our result performed that the cfDNA had
      significant prognostic value in predicting OS (HR = 2.41, 95%CI: 1.93-3.02, I2 =
      60%) and PFS (HR = 2.47, 95%CI: 1.80-3.40, I2 = 0%) in univariate analysis. The
      multivariate analyses about OS (HR = 2.57, 95%CI: 1.95-3.38, I2 = 66%) and PFS
      (HR = 2.31, 95%CI: 1.47-3.64, I2 = 0%) also showed significance. In conclusion,
      the cfDNA was a significant prognostic factor for OS and PFS in patients with
      pancreatic cancer. The mutation (Kras, ERBB2-exon17 and KrasG12V), circulating
      tumor DNA (ctDNA) presence, hypermethylation and higher concentration of cfDNA
      were both associated with worse survival results in pancreatic cancer.

PMID- 30227252
TI  - Deep sequencing discovery of causal mtDNA mutations in a patient with unspecific
      neurological disease.
AB  - Mitochondrial diseases (MD) are a group of diseases that can be caused by either
      mutations in the mitochondrial genome or nuclear DNA. MD may be difficult to
      diagnose since very often they are highly heterogeneous and with overlapping
      phenotypes. Molecular genomics approaches, especially NGS have helped in this
      sense. In this study we have sequenced the mitochondrial genome of a girl with an
      unspecific neurological disorder and her mother. The later, while neurologically
      unaffected, suffers from a myopathy without clear cause. We were able to detect
      two non-synonymous mutations in the MT-ATP6 gene, which we propose are strong
      candidates for causative agents. 9017C as the main candidate present at high
      heteroplasmy frequency in the patient (83,2%) and moderate in the mother (45,4%)
      while it has a low frequency in the general population. It might act alone or in
      conjunction with 9010A as an accessory mutation. Evolutionary analysis showed
      that both mutations were located in a critical position in the F0 a subunit, from
      F0-F1 ATPase. Functional studies showed that carriers of those mutations in
      comparison to an unaffected individual (father) presented a decrease in the basal
      and ATP-dependent oxygen consumption rate and a decrease in the maximum
      respiration rate.

PMID- 30227253
TI  - Integrative analysis identified mediation effects of lncRNAs on the correlations
      between methylation and mRNA.
AB  - The aim of this study was to construct DNA methylation-lncRNA-mRNA interaction
      trios in peripheral blood mononuclear cells. We first conducted eQTL analyses
      using genome-wide methylation, lncRNA and mRNA expression data from 43 Chinese
      females. Next, causal inference test (CIT) was used to detect the lncRNA
      mediation effects on methylation and mRNA. Methylation-lncRNA cis-eQTL analysis
      identified 11 significant cis-methylation-lncRNA pairs. Combined with the results
      from the next lncRNA-mRNA eQTL and methylation-mRNA eQTL analyses, the 11
      significant pairs and their corresponding 11,204 target e-mRNAs formed 12,245
      trios. Further CIT identified six lncRNAs as mediators in regulating the
      corresponding pairs between methylation and mRNA. This study detected lncRNAs
      with mediation effects on the correlations between DNA methylations and a large
      number of mRNAs.

PMID- 30227254
TI  - Transcriptome analysis and histopathology of black carp (Mylopharyngodon piceus)
      spleen infected by Aeromonas hydrophila.
AB  - Aeromonas hydrophila causes serious economic losses to the black carp
      (Mylopharyngodon piceus) industry. In this study, we analyzed the spleen of
      disease-resistant and susceptible black carp by RNA-seq. Overall, a total of 5243
      terms were enriched in the gene ontology (GO) analysis, and 323 related pathways
      were found in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment
      analysis. A total of 1935 differentially expressed genes were found and were
      primarily involved in cell adhesion, pathogen recognition, cellular immunity,
      cytokines, complement systems, and iron transport. Sixteen of the differently
      expressed genes involved in the immune response and the accuracy of the
      transcriptome data were further validated by quantitative real-time PCR (qRT
      PCR). We observed Tissue sections of the spleen infected with A. hydrophila and
      the control group and found that the spleen of the infected group had necrosis.

PMID- 30227255
TI  - Molecular characterization and functional analysis of IL-12p40 from Chinese sea
      bass (Lateolabrax maculatus) under biotic and abiotic stresses.
AB  - Interleukins are critical cytokines that are ubiquitously present in both
      vertebrates and invertebrates and constitute the front line of host innate
      immunity. Here, we identified and analyzed IL-12p40 from the Chinese sea bass
      Lateolabrax maculatus (LmIL-12p40). The LmIL-12p40 gene is expressed as a 1386
      base pair transcript that encodes a polypeptide of 321 amino acids.
      Transcriptional expression analysis indicated that LmIL-12p40 mRNA was
      ubiquitously expressed in all tested tissues and had a comparatively high
      expression level in immune-associated tissues (head-kidney and intestines).
      Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR)
      experiments showed that, after Vibro harveyi and Streptococus agalactiae
      infection, LmIL-12p40 mRNA expression was significantly up-regulated in the
      spleen, liver and head-kidney. To further clarify the immune function of LmIL
      12p40 after bacterial challenge, the recombinant LmIL-12p40 protein was acquired
      using a prokaryotic expression method. Furthermore, the LmIL-12p40 dimer (LmIL
      12p80) could be produced via protein-protein interactions by incubating p40
      monomer expressed from the pET28a vector (pET28a-LmIL-12p40) with p40 monomer
      expressed from the pGEX4T-1 vector (pGEX4T-1-LmIL-12p40). The antimicrobial
      activity of the purified LmIL-12p40 and LmIL-12p80 proteins were further studied
      in vitro using a bacterial growth inhibition test (for both liquid and solid
      cultures) and in vivo (using a bacterial growth inhibition test with the head
      kidney tissues). Furthermore, BL21 (DE3) E. coli cells transformed with the
      recombinant pET28a-LmIL-12p40 vector were dramatically protected in response to
      metal toxicity and H2O2-related oxidative stress. In summary, this study will
      provide foundational information regarding the role of LmIL-12p40 in defending
      against various biotic and abiotic stresses in fishes, which should help to
      further clarify the functional mechanism of interleukins.

PMID- 30227256
TI  - Physiopathological responses of sole (Solea senegalensis) subjected to bacterial
      infection and handling stress after probiotic treatment with autochthonous
      bacteria.
AB  - This study aimed to evaluate the protective effects of four autochthonous
      bacteria isolated from juvenile sole (Solea senegalensis) intestine as dietary
      probiotic supplement against bacterial pathogen infection and handling/transport
      stressors. Growth performance and immune responses were evaluated after 85 days
      of feeding trial. Sole (IBW = 16.07 +/- 0.11 g) were fed six experimental diets,
      a control diet (CTRL, without the dietary probiotic supplementation), and five
      diets supplemented with probiotic bacteria: PB1 (Shewanella hafniensis), PB2
      (Enterococcus raffinosus), PB3 (Shewanella hafniensis + Arthrobacter soli), PB4
      (Pseudomonas protegens + Arthrobacter soli) and PB5 (Shewanella hafniensis +
      Arthrobacter soli + Enterococcus raffinosus). All bacteria were selected based on
      their in vitro antimicrobial activity. After the growth trial, fish were
      submitted to a stress factor (transport) and then each dietary group was divided
      in two additional groups: non-infected (placebo) and infected with Photobacterium
      damselae subsp. piscicida. Immune and antioxidant responses were evaluated at day
      10 post-infection. In infection trial A, fish were infected on the same day of
      transport, whereas in trial B fish were infected after a 7-day recovery from the
      transport stress. At the end of the feeding trial, fish fed with PB2 and PB4
      showed lower final body weight when compared with the other dietary groups.
      Respiratory burst activity and nitric oxide production were not affected by
      probiotic supplementation. Fish fed with PB5 presented lower peroxidase activity
      compared to CTRL. Lysozyme and alternative complement pathway activity (ACH50)
      showed no significant differences between treatments. The innate immune responses
      were significantly affected after handling stress and bacterial infection. In
      trial A, the ACH50 levels of infected fish were significantly lower than the
      placebo groups. On the other hand, in trial B fish infected with Pdp demonstrated
      higher ACH50 levels when compared to placebos. Peroxidase levels were strongly
      modulated by bacterial infection and handling stress. In trials A and B,
      infection had a clear downgrade effect in peroxidase levels. Lipid peroxidation,
      catalase, glutathione S-transferase and glutathione reductase were altered by
      both bacterial infection and transport. Overall, dietary probiotic
      supplementation did not influence growth performance of sole. The immune and
      oxidative defenses of sole responded differently to infection depending on the
      probiotic and the synergy between pathogen infection and transport.

PMID- 30227257
TI  - Ontogeny of lymphoid organs and mucosal associated lymphoid tissues in meagre
      (Argyrosomus regius).
AB  - This study investigates the development of lymphoid organs and mucosal tissues in
      larval and juvenile meagre, Argyrosomus regius. For this purpose, meagre larvae
      were reared from hatch to the juvenile stage, under mesocosm conditions at 18-19 
      degrees C, using standard feeding sequences with live prey and artificial food.
      The kidney was evident upon hatch and included a visible pronephros, with
      undifferentiated stem cells and excretory tubules at 1 dph (3.15 +/- 0.1 mm SL).
      The thymus was first detected 8 dph (4.49 +/- 0.39 mm SL) and was clearly visible
      12 dph (5.69 +/- 0.76 mm SL), 33 dph (15.69 +/- 1.81 mm SL) an outer thymocytic
      zone and inner epithelial zone were visible. The spleen was present 12 dph,
      located between exocrine pancreas and intestine and by 26 dph (11.84 +/- 1.3 mm
      SL) consisted of a mass of sinusoids filled with red blood cells.
      Melanomacrophage centers were found 83 dph (66.25 +/- 4.35 mm SL) in the spleen.
      Between 14-15 dph (6.9 +/- 1.1 mm SL), goblet and rodlet cells appear in the gill
      and intestinal epithelium. The lymphoid organs, which appear in the order of
      pronephric kidney (1 dph), thymus (8 dph) and spleen (12 dph) remarkably increase
      in size during the post-flexion stage. While functional studies are needed to
      confirm the activity of the immune response, the morphology of the lymphoid
      organs suggest that meagre is not immuno-competent until 83 dph.

PMID- 30227258
TI  - Evaluation of the local effect of nonsurgical periodontal treatment with and
      without systemic antibiotic and photodynamic therapy in generalized aggressive
      periodontitis. A randomized clinical trial.
AB  - BACKGROUND: This study's aim was to evaluate the local effect of clarithromycin
      associated with antimicrobial photodynamic therapy (aPDT) in the treatment of
      generalized aggressive periodontitis. MATERIALS AND METHODS: The study sample
      comprised 72 periodontal pockets on single-rooted teeth in multiple quadrants,
      with both probing depth and clinical attachment level >=5 mm, and with bleeding
      on probing. The pockets were randomly distributed into four groups (n = 18 each)
      that received ultrasonic periodontal debridement in addition to placebo (the UPD
      group), systemic clarithromycin (the UPD + CLM group), aPDT (the UPD + aPDT
      group), or both systemic clarithromycin and aPDT (the UPD + CLM + aPDT group).
      The measurements were performed prior to treatment (baseline) and at 3 and 6
      months postoperatively. The following parameters were evaluated: plaque index,
      bleeding on probing, probing depth, gingival recession, and clinical attachment
      level. A 5% significance level was used in the statistical analysis. RESULTS: At
      3 months, UPD + aPDT, UPD + CLM, and UPD + CLM + aPDT groups all exhibited
      reduced probing depths relative to the UPD group (p <  0.05). However, at 6
      months, the reduction in mean probing depth was greater in the antibiotic groups
      (UPD+CLM and UPD+CLM+aPDT) than in the UPD and UPD+aPDT groups (p <  0.05).
      Regarding clinical attachment level, only the UPD+CLM+aPDT group presented a
      significant gain relative to the UPD and UPD + PDT groups (p <  0.05).
      CONCLUSIONS: Ultrasonic periodontal debridement has greater clinical advantages
      when associated with clarithromycin than with associated with aPDT. However, the
      joint application of aPDT and clarithromycin did not present additional benefits.

PMID- 30227259
TI  - Immunopotentiating effect of Inonotus obliquus fermentation products administered
      at vaccination in chickens.
AB  - Vaccination is an important approach for the control of avian viral diseases. The
      aim of this study was to evaluate the immune-potentiating effect of oral
      administration of Inonotus obliquus fermentation products (IOFP) at vaccination
      in chickens. In total, 120 one-day-old specific-pathogen-free chickens were
      randomly assigned to six groups: groups 1 to 3 were vaccinated with Newcastle
      disease virus (NDV) LaSota live vaccine via intranasal and eye-dropped route at
      seven days of age, and boosted two weeks later. Before each immunization,
      chickens in groups 1 and 2 were orally administered 0.8% IOFP and 0.2% astragalus
      polysaccharide (APS) in their diets, respectively, for seven consecutive days and
      group 3 was fed with commercial diet. At the same time, group 4, 5 and 6 were
      inoculated in the same manner with PBS and fed with commercial diet, containing
      0.8% IOFP and 0.2% APS diet, respectively, as negative controls. At 0, 7, 14, 21,
      28, and 35 days post-inoculation (dpi) firstly, the temporal changes in serum
      Newcastle disease hemagglutination inhibition (HI) and neutralizing antibody
      titers were determined. Meanwhile, proliferations of peripheral blood mononuclear
      cells (PBMCs) isolated from each group in response to concanavalin A stimulation
      and the expression levels of Th1-type (IFN-gamma) and Th2-type (IL-4) cytokines
      were determined by 3-(4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide,
      and ELISA methods. On days 0, 14 and 28 after the first vaccination, the
      percentages of CD3+, CD3+CD8+, and CD3+CD4+ T lymphocytes were detected by flow
      cytometry. At 35 dpi, a challenge test was carried out and protective efficacy
      was determined. Results showed that oral administration of IOFP could
      significantly enhance ND HI and neutralizing antibody titers, proliferation of
      PBMCs, proportions of CD3+, CD3+CD8+, and CD3+CD4+ T lymphocytes, as well as the
      ratio of Th1/Th2, and all of these values were superior to those seen with APS as
      a positive control, and other groups. Therefore, IOFP possesses significant
      immune-potentiating properties in chickens and may be a more economical and
      convenient oral adjuvant to improve vaccination in avian species.

PMID- 30227260
TI  - Improvement of glucocorticoid-impaired thymus function by dihydromyricetin via up
      regulation of PPARgamma-associated fatty acid metabolism.
AB  - T lymphocytes produced by the thymus are essential mediators of immunity.
      Accelerated thymic atrophy appears in the patients with administration of
      glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and
      infectious diseases, leading to dysregulation of immunity with manifestation of
      progressive diminution of new T cell production. However, there is no ideal
      method to overcome such side effects of GCs. In the current study, we proposed a
      composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a
      medicinal plant, which could protect from DEX-induced thymus damage and
      simultaneously enhance the anti-inflammatory effect of DEX. In the current study,
      we found that DEX-damaged thymic cellularity and architecture, reduced thymocyte
      numbers, induced thymocyte apoptosis and dropped CD4+ and CD8+ double positive T
      cell numbers in thymus which was effectively improved by co-treatment with DMY.
      Quantification of signal joint TCR delta excision circles (TRECs) and Vbeta TCR
      spectratyping analysis were employed to determine the thymus function with
      indicated treatments. The results showed that DEX-impaired thymus output and
      decreased TCR cell diversity which was ameliorated by co-treatment with DMY.
      iTRAQ 2D LC-MS/MS was applied to analyze the proteomic profiling of thymus of
      mice treated with or without indicated agents, followed by informatics analysis
      to identify the correlated signaling pathway. After validated by Western blotting
      and Real-time PCR, we found that PPARgamma-associated fatty acid metabolism was
      increased in the thymic tissues of the animals treated with DMY plus DEX than the
      animals treated with DEX alone. The agonist and antagonist of PPARgamma were
      further employed to verify the role of PPARgamma in the present study.
      Furthermore, DMY demonstrated a synergistic effect with co-administration of DEX
      on suppressing inflammation in vivo. Collectively, DMY relieved thymus function
      damaged by DEX via regulation of PPARgamma-associated fatty acid metabolism. Our
      findings may provide a new strategy on protection of thymus from damage caused by
      GCs by using appropriate adjuvant natural agents through up-regulation of
      PPARgamma-associated fatty acid metabolism.

PMID- 30227261
TI  - Preventing childhood and lifelong disability: Maternal dietary supplementation
      for perinatal brain injury.
AB  - The majority of brain injuries that lead to cerebral palsy, developmental
      disability, and mental health disorders have their onset in utero. These lifelong
      conditions come with great economic and emotional burden as they impact function
      in nearly all domains of affected individuals' lives. Unfortunately, current
      therapeutic options are limited. There remains a focus on rescue, rehabilitation,
      and regeneration after the injury has occurred, rather than aiming to prevent the
      initial injury. Prevention would imply treating the mother during pregnancy to
      alter the fetal environment and in turn, treat the fetus. Fear of harming the
      developing fetus remains as a result of errors of the past such as the release of
      thalidomide. In this review, we outline evidence from animal studies and clinical
      trials that have explored maternal dietary supplementation with natural health
      products (including nutraceuticals and functional foods) for perinatal brain
      injury prevention. Namely, we discuss magnesium sulphate, creatine, choline,
      melatonin, resveratrol and broccoli sprouts/sulforaphane. Although clinical
      trials have only been completed in this realm for magnesium sulphate, results in
      animal models have been promising, suggesting that this is a productive avenue
      for further research. Natural health products may provide safe, effective,
      affordable, and easily accessible prevention of fetal brain injury and resulting
      lifelong disabilities.

PMID- 30227262
TI  - Detection of laminar resorption in osteo-odonto-keratoprostheses.
AB  - PURPOSE: To compare the clinical examination and computerized tomography (CT)
      scanning methods for the detection of laminar resorption in eyes with osteo
      odonto-keratoprosthesis (OOKP). METHODS: Patients who developed laminar
      resorption after OOKP surgery and had at least one CT scan of the lamina during
      the follow-up were included. Case records and CT images and reports were
      retrospectively reviewed. Each lamina of the eye was regarded as a case. The
      imaging and clinical data were collected in Microsoft Excel, and statistical
      analysis was performed on Stata-v14. The agreements and sensitivities of both the
      methods were compared. RESULTS: Forty patients out of 64 were found to have
      laminar resorption. A total of 48 laminae were studied, which had data on the
      presence or absence of resorption. The sensitivity and specificity of clinical
      detection of resorption were 87.5% (CI 68%-97%) and 37.5% (CI 8.5%-75.5%),
      respectively. Whereas, the sensitivity and specificity of CT scan were 81% (CI
      61%-93%) and 50% (CI12%-88%), respectively. Both the methods have detected
      resorption in 21 out of 32 laminae having both the clinical and CT scan data.
      There is a fair agreement between the two techniques in the identification of
      thinned laminar sites. CONCLUSIONS: Clinical detection of laminar resorption in
      OOKP eyes is equally sensitive to the CT scanning. Resorption can be detected
      even in its early stages by clinical palpation in experienced hands. Frequent CT
      scanning is not indicated to detect laminar resorption. Both methods complement
      each other. Thinned laminar segments should be compared and correlated with both
      the methods for full evaluation of resorption.

PMID- 30227263
TI  - Comprehensive evaluation of the greater sciatic notch for sexual estimation
      through three-dimensional metric analysis using computed tomography based models.
AB  - The greater sciatic notch is an effective indicator for sexual estimation, which
      is the initial process to identify unknown skeleton. Visual assessment is the
      mainstream of analysis methods; however, the subjectivity of researchers is also
      questioned. Metric method using three-dimensional models reconstructed from
      radiographic images can ensure reproducible and stable measurement of the greater
      sciatic notch. In this study, the greater sciatic notch was analyzed in various
      manners, including distances, angles, and dimensions, with the aid of an
      automatic measurement program and a landmark verification system. Among 28 items,
      15 measurements showed more than 85% accuracy. Measurements related to the
      posterior part of the greater sciatic notch near the posterior inferior iliac
      spine particularly showed higher accuracy (93.1%). To test this observation,
      "arithmetic posterior angle of the greater sciatic notch", a generalized form of
      partial angle of the greater sciatic notch, was designed. It showed more than 90%
      accuracy. When the results of the three-dimensional measurements were applied to
      classify dry bones, it proved to be valid in contemporary Korean population. The
      method and results of this study can be referenced in wider use of the greater
      sciatic notch analysis.

PMID- 30227264
TI  - Tattoo image composed of radiopaque deposits demonstrated by postmortem computed
      tomography.
AB  - Postmortem computed tomography (PMCT) is becoming used more commonly in routine
      forensic investigation. CT is sensitive for detection of metal foreign bodies.
      Here we report a case of suicide due to self-ignition of kerosene that the victim
      had poured over herself. Prior to autopsy, PMCT detected tiny radiopaque
      particles arranged in a row in the surface of the back and either thigh, together
      with a series of similar particles under the skin lateral to the breasts or the
      bilateral inguinal region. At autopsy, external examination revealed third-degree
      burns involving charred tissues all over the body except for the head. Tattoos
      were visible on the back and on either thigh. The tattoos had colored designs,
      and the red portions corresponded to the radiopaque particles in the surface of
      the body. Internal examination demonstrated swelling of the axillary and inguinal
      lymph nodes, which corresponded to the radiopaque particles. A wave length
      dispersive X-ray spectroscopy revealed deposition of mercury and titanium in the
      inguinal lymph nodes. Thus, it was plausible that the ink could have contributed
      to the radiopaque particles found by PMCT in the surface of the back and thighs,
      as well in the lymph nodes. The present case was able to provide clues for
      interpretation of radiopaque particles revealed by PMCT in the surface of the
      body.

PMID- 30227265
TI  - New nano-biomaterials for the removal of malachite green from aqueous solution
      via a response surface methodology.
AB  - The development of new biomaterials for the remove of organic contaminants from
      wastewater has attracted much attention over the few past years. One of the most
      cost-effective approaches is to produce new high value biomaterials from low
      value solid agricultural biowastes. In this work, sugarcane bagasse and
      agricultural waste rich in reducing sugars, acted as both a green bioreductant
      for graphene oxide (GO) and a sustainable supporter for the immobilization of
      Burkholderia cepacia. Therefore, this new biomaterial which contained both
      reduced graphene oxide (RGO) and Burkholderia cepacia, was cable of initial
      adsorption of malachite green (MG) and its subsequent biodegradation. After 60 h,
      immobilized Burkholderia cepacia degraded more MG (98.5%) than a cell cultured
      Burkholderia cepacia (87.7%) alone. Raman spectroscopy confirmed that GO was
      successfully reduced by bagasse and that consequently a composite (B-RGO) was
      prepared. SEM indicated that Burkholderia cepacia was well immobilized and
      kinetics studies showed that the adsorption of MG onto the developed composite
      fitted a pseudo-second order kinetics model (R2 > 0.99). Biodegradation of MG,
      was confirmed by the detection of appropriate degradation products such as N, N
      dimethylaniline and 4-(Dimethylamino) benzophenone using GC-MS, UV and FT-IR, and
      via best fit first-order biodegration kinetics. Furthermore, a response surface
      methodology (RSM) was applied to the removal process by varying four independent
      parameters using a Box-Behnken design (BBD). Optimum MG removal (99.3%) was
      achieved at 31.5  degrees C, with an initial MG concentration of 114.5 mg L-1,
      initial pH of 5.85, and an adsorbent dosage of 0.11 g L -1. The excellent removal
      efficiency indicated that agricultural waste derived reduced graphene oxide bio
      adsorbents have significant potential for the removal of dyes such as MG from
      industrial wastewaters.

PMID- 30227266
TI  - Prediabetes and cardiovascular disease risk: A nested case-control study.
AB  - BACKGROUND AND AIMS: We aimed to examine the risk of cardiovascular disease (CVD)
      with persistent prediabetes during the last four years prior to a CVD event in a
      large occupational cohort in Japan. METHODS: We performed a nested case-control
      study using data from the Japan Epidemiology Collaboration on Occupational Health
      Study. A total of 197 registered cases of CVD were identified and matched
      individually with 985 controls according to age, sex, and worksite. Prediabetes
      was defined as fasting plasma glucose 100-125 mg/dL and/or HbA1c 5.7-6.4%.
      Persistent prediabetes was defined as having prediabetes at years one and four
      prior to the onset/index date; persistent normoglycemia was similarly defined.
      Associations between prediabetes and CVD risk were assessed using conditional
      logistic regression models. RESULTS: Compared with people with persistent
      normoglycemia over the four years prior to the onset/index date, the unadjusted
      odds ratio (95% confidence interval) for CVD was 2.88 (1.56, 5.32) for people
      with persistent prediabetes. After adjusting for BMI, smoking, hypertension, and
      dyslipidemia assessed four years before the onset/index date, the association was
      slightly attenuated to an OR (95% confidence interval) of 2.62 (1.31, 5.25).
      Prediabetes assessed at single time points was also associated with an elevated
      risk of CVD, with multivariable-adjusted odds ratio (95% confidence interval) of
      1.72 (1.12, 2.64) and 2.13 (1.32, 3.43) for prediabetes at one and four years
      prior to the onset/index date, respectively. CONCLUSIONS: Prediabetes is
      associated with an increased risk of CVD. Identification and management of
      prediabetes are important for the prevention of CVD.

PMID- 30227267
TI  - Regional coronary endothelial dysfunction is related to the degree of local
      epicardial fat in people with HIV.
AB  - BACKGROUND AND AIMS: Coronary artery disease (CAD) is now an important cause of
      premature death in people with HIV but the causes of accelerated CAD are poorly
      understood. Epicardial adipose tissue (EAT) is metabolically-active and thought
      to contribute to CAD development. We tested the hypothesis that abnormal coronary
      endothelial function (CEF), an early marker and mediator of atherosclerosis, is
      related to the amount of local pericoronary EAT in HIV. METHODS: We studied 36
      participants with HIV and no CAD (HIV+ CAD-), 15 participants with HIV and known
      CAD (HIV+ CAD+), and 14 age-matched, healthy participants without HIV (HIV-CAD-).
      To measure CEF, coronary MRI was performed before and during isometric handgrip
      exercise (IHE), an endothelial-dependent stressor. EAT was measured with MRI at
      the same imaging plane as CEF. RESULTS: CEF was significantly depressed, as
      measured by IHE-induced % coronary cross sectional area (CSA) change, in HIV+ CAD
      and HIV+ CAD+ as compared to HIV-CAD-participants (p<0.0001). EAT thickness was
      significantly greater in HIV+ CAD- and HIV+ CAD+ participants as compared to HIV
      CAD-participants (p=0.001). There was a significant inverse relationship between
      CEF and local EAT thickness and area (R = -0.48 and R = -0.51 respectively,
      p<0.0001 for both) among participants with HIV even after adjustment for
      cardiovascular risk factors. In participants with multiple CEF measures, CEF was
      lower in segments with higher EAT, other factors being equivalent. CONCLUSIONS:
      There is a significant relationship between increased metabolically-active EAT
      and depressed local CEF in people with HIV, consistent with the hypothesis that
      increased epicardial fat contributes to accelerated CAD in persons with HIV.

PMID- 30227269
TI  - A novel S-nitrosocaptopril monohydrate for pulmonary arterial hypertension: H2O
      and -SNO intermolecular stabilization chemistry.
AB  - S-nitrosocaptopril (CapNO) possesses dual capacities of both Captopril and an NO
      donor with enhanced efficacy and reduced side effects. CapNO crystals are
      difficult to make due to its unstable S-NO bond. Here, we report a novel stable S
      nitrosocaptopril monohydrate (CapNO.H2O) that is stabilized by intermolecular
      five-membered structure, where one H of H2O forms a hydrogen bond with O- of the
      stable resonance zwitterion Cap-S+=N-O-, and the O in H2O forms the dipole-dipole
      interaction with S+ through two unpaired electrons. With the chelation and common
      ion effect, we synthesized and characterized CapNO.H2O that is stable at 4 
      degrees C for 180 days and thereafter without significant degradation. Compared
      to Captopril, CapNO showed direct vasorelaxation and beneficial effect on PAH
      rats, and could be self-assembled in rat stomach when Captopril and NaNO2 were
      given separately. This novel CapNO.H2O with low entropy paves an avenue for its
      clinical trials and commercialization.

PMID- 30227268
TI  - Respiratory muscle activation patterns during maximum airway pressure efforts are
      different in women and men.
AB  - Maximum inspiratory and expiratory pressure values (PImax and PEmax) are indirect
      measures of respiratory muscle strength that, in healthy adults, are known to be
      significantly lower in women compared to men. In part, sex differences in
      breathing kinematics, lung size, body composition, muscle mass, and muscle fiber
      composition are thought to be responsible for these effects. However, it is not
      known whether respiratory muscle activation during maximum respiratory efforts is
      also sex-specific. In this study, we addressed whether respiratory multi-muscle
      activation patterns during PImax and PEmax efforts are different between healthy
      women and men. Forced vital capacity (FVC), forced expiratory volume in one
      second (FEV1), PImax, PEmax, and surface electromyographic (sEMG) activity
      recorded from respiratory muscles during these maximum airway pressure efforts
      were obtained in 13 women and 11 men. Percent predicted values of FVC and FEV1
      were not significantly different in these two groups (women vs. men: 112 +/- 14
      vs. 105 +/- 15%, p = 0.29; and 92 +/- 12 vs. 93 +/- 13, p = 0.82, Mean +/- SD,
      respectively), while PImax and PEmax measures were significantly lower in women
      compared to men (68 +/- 16 vs. 88 +/- 19 cmH2O, p = 0.011; and 69 +/- 13 vs. 94
      +/- 17, p = 0.0004, respectively). Using vector-based methodology, by calculating
      the Similarity Index (SI) as measure of the resemblance between two sEMG patterns
      and the Magnitude (Mag) representing the overall amount sEMG during motor task,
      we have found that although the Mag values for both PImax and PEmax tasks were
      not significantly different in two groups, the SIs revealed significant sex
      dependent differences in muscle activation patterns (0.89 +/- 0.08 vs. 0.97 +/-
      0.02, p = 0.016; and 0.77 +/- 0.11 vs. 0.92 +/- 0.04, p = 0.0006, respectively).
      During the PImax effort, presented as the percentage of total sEMG amplitude,
      activity of upper trapezius muscle was significantly larger (p = 0.001) while
      activation of rectus abdominus, oblique, and lower paraspinal muscles were
      significantly smaller (p = 0.002, p = 0.040, p = 0.005, respectively) in women
      when compared to the men (50 +/- 21 vs. 22 +/- 11%; 2 +/- 2 vs. 8 +/- 7; 4 +/- 3
      vs. 9 +/- 7, 2 +/- 3 vs. 7 +/- 6, respectively). During PEmax effort, the
      percentage of sEMG activity were significantly larger in upper and lower
      trapezius, and intercostal muscles (p = 0.038, p = 0.049, p = 0.037,
      respectively) and were significantly smaller in pectoralis, rectus abdominus, and
      oblique muscles (p = 0.021, p < 0.0001, p = 0.048, respectively) in women
      compared to men (16 +/- 10 vs. 9 +/- 4%; 16 +/- 9 vs. 8 +/- 5; 36 +/- 12 vs. 25
      +/- 9; 6 +/- 3 vs. 15 +/- 5; 14 +/- 5 vs. 20 +/- 7, respectively). These findings
      indicate that respiratory muscle activation patterns during maximum airway
      pressure efforts in healthy individuals are sex-specific. This information should
      be considered during respiratory motor control evaluation and treatment planning
      for people with compromised respiratory motor function.

PMID- 30227270
TI  - Enhancing the activity and stability of Mn-superoxide dismutase by one-by-one
      ligation to catalase.
AB  - Dismutation of superoxide by superoxide dismutase (SOD) generates hydrogen
      peroxide, which may be reduced to hydroxyl radical. The generated H2O2 during the
      catalysis can have an oxidative damage to SOD. Hydrogen peroxide decomposition by
      catalase (CAT) can help circumvent the problem. Mn-superoxide dismutase (herein
      referred to as SOD) and CAT are dimeric and tetrameric proteins, respectively.
      Herein, through intein-mediated in vivo subunit splicing, the C-terminus of the
      CAT subunit (CATS) has been specifically ligated to the N-terminus of the SOD
      subunit (SODS) with a peptide bond. Thus, the splicing product SOD&CAT combines
      the superoxide anion (*O2-) scavenging ability and the ability of decomposing
      H2O2. The in vivo subunit splicing has little effect on the secondary structures
      of the enzymes as confirmed by circular dichroism (CD) spectra. Fluorescence
      spectra showed that the splicing product SOD&CAT has a higher stability than SOD.
      In the splicing product SOD&CAT, the SOD subunits are in close proximity to the
      CAT subunits, facilitating immediate transfer of H2O2 between the enzymes and
      enabling efficient decomposition of H2O2. SOD&CAT exhibited a superoxide anion
      (*O2-) scavenging ability 244% higher than that of SOD and 46% higher than that
      of the mixed enzymes SOD+CAT.

PMID- 30227271
TI  - ALK3 undergoes ligand-independent homodimerization and BMP-induced
      heterodimerization with ALK2.
AB  - The bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 are essential
      for expression of hepcidin, a key iron regulatory hormone. In mice, hepatocyte
      specific Alk2 deficiency leads to moderate iron overload with periportal liver
      iron accumulation, while hepatocyte-specific Alk3 deficiency leads to severe iron
      overload with centrilobular liver iron accumulation and a more marked reduction
      of basal hepcidin levels. The objective of this study was to investigate whether
      the two receptors have additive roles in hepcidin regulation. Iron overload in
      mice with hepatocyte-specific Alk2 and Alk3 (Alk2/3) deficiency was characterized
      and compared to hepatocyte-specific Alk3 deficient mice. Co-immunoprecipitation
      studies were performed to detect the formation of ALK2 and ALK3 homodimer and
      heterodimer complexes in vitro in the presence and absence of ligands. The iron
      overload phenotype of hepatocyte-specific Alk2/3-deficient mice was more severe
      than that of hepatocyte-specific Alk3-deficient mice. In vitro co
      immunoprecipitation studies in Huh7 cells showed that ALK3 can homodimerize in
      absence of BMP2 or BMP6. In contrast, ALK2 did not homodimerize in either the
      presence or absence of BMP ligands. However, ALK2 did form heterodimers with ALK3
      in the presence of BMP2 or BMP6. ALK3-ALK3 and ALK2-ALK3 receptor complexes
      induced hepcidin expression in Huh7 cells. Our data indicate that: (I) ALK2 and
      ALK3 have additive functions in vivo, as Alk2/3 deficiency leads to a greater
      degree of iron overload than Alk3 deficiency; (II) ALK3, but not ALK2, undergoes
      ligand-independent homodimerization; (III) the formation of ALK2-ALK3
      heterodimers is ligand-dependent and (IV) both receptor complexes functionally
      induce hepcidin expression in vitro.

PMID- 30227272
TI  - Targeting mitochondrial dysfunction and oxidative stress in heart failure:
      Challenges and opportunities.
AB  - Mitochondrial dysfunction characterized by impaired bioenergetics, oxidative
      stress and aldehydic load is a hallmark of heart failure. Recently, different
      research groups have provided evidence that selective activation of mitochondrial
      detoxifying systems that counteract excessive accumulation of ROS, RNS and
      reactive aldehydes is sufficient to stop cardiac degeneration upon chronic
      stress, such as heart failure. Therefore, pharmacological and non-pharmacological
      approaches targeting mitochondria detoxification may play a critical role in the
      prevention or treatment of heart failure. In this review we discuss the most
      recent findings on the central role of mitochondrial dysfunction, oxidative
      stress and aldehydic load in heart failure, highlighting the most recent
      preclinical and clinical studies using mitochondria-targeted molecules and
      exercise training as effective tools against heart failure.

PMID- 30227273
TI  - Cancer-specific chemotherapeutic strategy based on the vitamin K3 mediated ROS
      regenerative feedback and visualized drug release in vivo.
AB  - A promising theranostic nanosystem VK3-CPT@Ru-CD is designed and fabricated by
      the host-guest driven self-assembly between the fluorescent adamantine
      functionalized Ru(II) complexes and the ROS-labile-cyclodextrin modified
      thioketal linkers, in which anticancer drug camptothecin (CPT) and vitamin K3
      (VK3) are effectively co-encapsulated. On account of the generative feedback
      between the intracellular redox cycling of VK3 and the high degree of ROS
      triggered collapse of nanoparticles, VK3-CPT@Ru-CD can facilitate cancer-specific
      ROS amplification and drug release selectively in cancer cells, thus realizing
      the selective killing of tumor with minimal side-effects both in vitro and in
      vivo, the therapeutic effect of which is more prominent than the free anti-cancer
      drugs. More interestingly, the menadione structure of encapsulated VK3 can
      effectively quench the inherent fluorescence of Ru-CD, and a fluorescence
      lightening up phenomenon is observed accompanied with the ROS-triggered drug
      release, which can be utilized for real-time tracking of drug release in vitro
      and in vivo.

PMID- 30227276
TI  - Relationship between knee abduction moment with patellofemoral joint reaction
      force, stress and self-reported pain during stair descent in women with
      patellofemoral pain.

PMID- 30227274
TI  - The IS2 Element Improves Transcription Efficiency of Integration-Deficient
      Lentiviral Vector Episomes.
AB  - Integration-defective lentiviral vectors (IDLVs) have become an important
      alternative tool for gene therapy applications and basic research. Unfortunately,
      IDLVs show lower transgene expression as compared to their integrating
      counterparts. In this study, we aimed to improve the expression levels of IDLVs
      by inserting the IS2 element, which harbors SARs and HS4 sequences, into their
      LTRs (SE-IS2-IDLVs). Contrary to our expectations, the presence of the IS2
      element did not abrogate epigenetic silencing by histone deacetylases. In
      addition, the IS2 element reduced episome levels in IDLV-transduced cells.
      Interestingly, despite these negative effects, SE-IS2-IDLVs outperformed SE-IDLVs
      in terms of percentage and expression levels of the transgene in several cell
      lines, including neurons, neuronal progenitor cells, and induced pluripotent stem
      cells. We estimated that the IS2 element enhances the transcriptional activity of
      IDLV LTR circles 6- to 7-fold. The final effect the IS2 element in IDLVs will
      greatly depend on the target cell and the balance between the negative versus the
      positive effects of the IS2 element in each cell type. The better performance of
      SE-IS2-IDLVs was not due to improved stability or differences in the proportions
      of 1-LTR versus 2-LTR circles but probably to a re-positioning of IS2-episomes
      into transcriptionally active regions.

PMID- 30227275
TI  - Phenotypic miRNA Screen Identifies miR-26b to Promote the Growth and Survival of
      Endothelial Cells.
AB  - Endothelial cell (EC) proliferation is a crucial event in physiological and
      pathological angiogenesis. MicroRNAs (miRNAs) have emerged as important
      modulators of the angiogenic switch. Here we conducted high-content screening of
      a human miRNA mimic library to identify novel regulators of EC growth
      systematically. Several miRNAs were nominated that enhanced or inhibited EC
      growth. Of these, we focused on miR-26b, which is a conserved candidate and
      expressed in multiple human EC types. miR-26b overexpression enhanced EC
      proliferation, migration, and tube formation, while inhibition of miR-26b
      suppressed the proliferative and angiogenic capacity of ECs. A combinatory
      functional small interfering RNA (siRNA) screening of 48 predicted gene targets
      revealed that miR-26b enhanced EC growth and survival through inhibiting PTEN
      expression. Local administration of miR-26b mimics promoted the growth of new
      microvessels in the Matrigel plug model. In the mouse model of hindlimb ischemia,
      miR-26b was found to be downregulated in endothelium in the first week following
      ischemia, and local overexpression of miR-26b improved the survival of
      capillaries and muscle fibers in ischemic muscles. Our findings suggest that miR
      26b enhances EC proliferation, survival, and angiogenesis. miR-26b is a potential
      target for developing novel pro-angiogenic therapeutics in ischemic disease.

PMID- 30227277
TI  - Effect of foot orthosis design on lower limb joint kinematics and kinetics during
      walking in flexible pes planovalgus: A systematic review and meta-analysis.
AB  - BACKGROUND: Foot orthoses are commonly used for the management of excessive foot
      pronation in people with pes planovalgus. However, results are inconsistent due
      to variability in orthosis geometrical designs. This systematic review with meta
      analysis aimed to classify and investigate the effects of foot orthoses, based on
      their design, in terms of lower limb kinematics and kinetics in people with pes
      planovalgus. METHODS: Electronic databases were searched up until August 2017.
      Peer-reviewed journal studies including adult participants with flexible pes
      planovalgus and reporting kinematics and kinetics effects of foot orthoses during
      walking were included and classified based on the orthosis design. Eleven studies
      were retained and assessed according to methodological (mean 76.1%; range [63.2%
      84.2%] - high) and biomechanical (mean 71.6%; range [44.4%-100%] - moderate)
      qualities. Meta-analysis was performed by calculating the effect size, using
      standardized mean differences, between control and orthotics conditions.
      FINDINGS: Meta-analysis revealed less rearfoot eversion with the use of foot
      orthoses including medial forefoot or both forefoot and rearfoot posting.
      However, no significant effect of foot orthoses with arch support and neutral
      rearfoot posting to control excessive foot pronation were found. In terms of
      kinetics, none of the foot orthoses showed effects. INTERPRETATION: Using medial
      posting is the most effective foot orthotic feature to reduce the peak rearfoot
      eversion and to control excessive foot pronation. Nevertheless, heterogeneity
      between study protocols contributes to the low evidences of foot orthoses effects
      on kinematics and kinetics during walking in people with pes planovalgus.

PMID- 30227278
TI  - Changes in the ankle muscles co-activation pattern after 5 years following total
      ankle joint replacement.
AB  - BACKGROUND: The Hintegra(r) arthroplasty provides inversion-eversion stability,
      permits axial rotation, ankle flexion-extension, and improvements of the gait
      patterns are expected up to 12 months of rehabilitation. However, sensorimotor
      impairments are observed in ankle flexors/extensors muscles after rehabilitation,
      with potential negative effects on locomotion. Here we determined the timing and
      amplitude of co-activation of the tibialis anterior and medial gastrocnemius
      muscles during gait by assessing non-operated and operated legs of patients with
      total ankle replacement, 5 years after surgery. METHODS: Twenty-nine patients
      (age: 58 [5.5] years, height: 156.4 [6.5] cm, body mass: 72.9 [6.5] kg, 10 men,
      and 19 women) that underwent Hintegra(r) ankle arthroplasty were included.
      Inclusion criteria included 5 years prosthesis survivorship. The onset and offset
      of muscle activation (timing), as well as the amplitude of activation, were
      determined during barefoot walking at self-selected speed by surface
      electromyography. The timing, percentage, and index of co-activation between the
      tibialis anterior and medial gastrocnemius were quantified and compared between
      non-operated and operated legs. FINDINGS: The operated leg showed higher co
      activation index and temporal overlapping between tibialis anterior and medial
      gastrocnemius during gait (p < 0.001). INTERPRETATION: The neuromuscular changes
      developed during the process of degeneration do not appear to be restored 5 years
      following arthroplasty. The insertion of an ankle implant may restore anatomy and
      alignment but neuromuscular adaptations to degeneration are not corrected by 5
      years following joint replacement.

PMID- 30227279
TI  - Bereavement process of professional caregivers after deaths of their patients: A
      meta-ethnographic synthesis of qualitative studies and an integrated model.
AB  - BACKGROUND: Professional caregivers bereave after patients' deaths. Such
      bereavement can exert considerable influences on huge numbers of professional
      caregivers and their clients. No study, however, has synthesized scattered
      evidence on the core process of such bereavement, and no corresponding model
      exists. AIM: To systematically review and synthesize the experience of
      bereavement after patients' deaths, and in particular, its core process, in
      professional caregivers' own descriptions in existing literature, and to propose
      an integrated model on that basis. DESIGN: A review was conducted following
      Enhancing Transparency in Reporting the Synthesis of Qualitative Research
      Statement (ENTREQ). DATA SOURCE: CINAHL Plus, PubMed, PsycINFO, Scopus, Embase,
      and Web of Science were searched in April 2018 with keywords as combinations of
      "professional caregiver" and "bereavement". References of eligible studies from
      pre-planned searches were manually screened. REVIEW METHODS: Full-text and
      English-written qualitative studies published in peer-reviewed journals in or
      after 1980 were included. Their qualities were assessed by two of the authors
      independently. Meta-ethnography was employed to synthesize findings from previous
      studies. RESULTS: Twenty-three studies met the inclusion criteria, the majority
      conducted in Western and developed regions of the world. Three core concepts were
      identified in the core professional bereavement process: (1) perceived nature of
      patients' deaths; (2) bereavement reactions; (3) accumulated changes. Each
      concept consists of both a personal dimension and a professional dimension. Risk
      and protective factors and coping methods were unveiled to influence the core
      process. An integrated, process-oriented and multi-dimensional model was proposed
      on the basis of these findings. CONCLUSIONS: Patients' deaths are significant
      events for professional caregivers, and they bring both personal and
      professional, both temporal and long-lasting impacts. Professional bereavement is
      distinctive from familial bereavement and deserves serious attention for its own
      sake. Attention, acknowledgment, and in-time support must be given to
      professional caregivers when they encounter patients' deaths.

PMID- 30227280
TI  - An evaluation of high frequency turbidity as a proxy for riverine total
      phosphorus concentrations.
AB  - Surface water eutrophication resulting from excessive phosphorus (P) inputs is
      one of today's most challenging environmental issues. Riverine total phosphorus
      (TP) concentrations have high temporal variability, which complicates flux
      estimation. We evaluated the usefulness of high frequency in-situ turbidity
      measurements as a proxy for TP in Savjaan, a river draining a mixed land use
      catchment (722 km2) in central Sweden. Turbidity was monitored every 10th-15th
      minute during 6 consecutive years (2012-2017). Linear regression showed a good
      relationship between high frequency turbidity and TP (r2 = 0.64) and could hence
      be used for comparison of flux estimation methods. Predictive power of the
      turbidity-TP relationship was not improved by adding seasons, hydrograph
      rising/falling limb or high/low stream discharge to the model which argues for a
      single transfer function relating turbidity and TP. Both TP and turbidity were
      log-normally distributed. However, flux estimates were sensitive to data
      transformation; predicted TP concentrations and fluxes based on log-transformed
      data were biased towards lower concentrations and fluxes compared to non
      transformed data. In five of six years grab sample and high frequency estimated
      TP fluxes were similar (grab sample estimates -10% to +13% P transport compared
      to high frequency flux estimates). The exception was in 2013, when a 50-year
      spring flood occurred, and the grab sample estimated flux was 56% larger than
      that estimated from high frequency data. Thus, the flux comparisons were mostly
      affected by stream discharge, which underlines the importance of capturing high
      discharge episodes with, e.g. in situ sensors. While uncertainties regarding the
      use of turbidity as a proxy for TP remain, it is clear that credible water
      chemistry data can be obtained with current high frequency sensors. We conclude
      that high frequency data can be used to better understand catchment response to
      external pressures and gain insights into water quality that will be missed with
      grab sampling.

PMID- 30227282
TI  - Microbial mediated sedimentary phosphorus mobilization in emerging and eroding
      wetlands of coastal Louisiana.
AB  - The interactions between the microbial reduction of Fe (III) oxides and sediment
      geochemistry are poorly understood and mostly unknown for the Louisiana deltaic
      plain. This study evaluates the potential of P mobilization for this region
      during bacterially mediated redox reactions. Samples were collected from two
      wetland habitats (forested wetland ridge, and marsh) characterized by variations
      in vegetation structure and elevation in the currently prograding Wax Lake Delta
      (WLD) and two habitats (wetland marsh, and benthic channel) in degrading
      Barataria Bay in Lake Cataouatche (BLC). Our results show that PO43- mobilization
      from WLD and BLC habitats were negligible under aerobic condition. Under
      anaerobic condition, there is a potential for significant release of PO43- from
      sediment and wetland soils. PO43- release in sediments spiked with Fe reducing
      bacteria Shewanella putrefaciens (Sp-CN32) were significantly higher in all cases
      with respect to a control treatment. In Wax Lake delta, PO43- release from
      sediment spiked with Sp-CN32 increased significantly from 0.064+/-0.001 to
      1.460+/-0.005MUmolg-1 in the ridge and from 0.079+/-0.007 to 2.407+/-0.001MUmolg
      1 in the marsh substrates. In Barataria bay, PO43- release increased from 0.103+/
      0.006MUmolg-1 to 0.601+/-0.008MUmolg-1 in the channel and 0.050+/-0.000 to
      0.618+/-0.026MUmolg-1 in marsh substrates. The PO43- release from sediment
      slurries spiked with Sp-CN32 was higher in the WLD habitats (marsh 30-fold, ridge
      22-fold) compared to the BLC habitats (marsh 12-fold, channel 6-fold). The
      increase in PO43- release was significantly correlated with the Fe bound PO43- in
      sediments from different habitats but not with their organic matter content. This
      study contributes to our understanding of the release mechanism of PO43- during
      bacterial mediated redox reaction in wetland soils undergoing pulsing sediment
      deposition and loss.

PMID- 30227281
TI  - Re-thinking classical mechanistic model for pollutant build-up on urban
      impervious surfaces.
AB  - Accurate modelling of particulates build-up process is essential for designing
      effective stormwater management strategies. However, current modelling practice
      relies on the classical 'power model' which has limitations in accounting for the
      variability in the build-up process. This research study investigated the
      relationships between influential factors of the build-up process and
      coefficients in the power model. The outcomes showed that the coefficient, which
      determines the build-up rate, is predominantly influenced by land use factors
      (pervious area, road area, commercial area and residential area), such that land
      use factors exerted 23 times more influence than the site characteristics
      (distance to pervious area and road surface texture depth). The coefficient,
      which determines how quickly build-up reaches equilibrium, was found to be
      equally influenced by anthropogenic activities (sweeping frequency and traffic
      volume) and site characteristics. Further, site characteristics were found to
      play a major role in generating build-up process variability with three times
      more influence than that of anthropogenic activities. It was found that the power
      model satisfactorily replicates the build-up of particles <74 MUm. For the build
      up of particles >74 MUm, a new coefficient, namely, 'coefficient of variability'
      was introduced in order to improve the prediction performance (up to 17% compared
      to original power model). The study outcomes provide a deeper understanding into
      particulates build-up modelling, and can contribute to the formulation of
      effective stormwater treatment strategies.

PMID- 30227283
TI  - Shelter, clothing, and fuel: Often overlooked links between soils, ecosystem
      services, and human health.
AB  - There are clear connections between ecosystem services (ES) and human health, as
      well as between soils and human health. However, studies to date have not
      investigated links between soil ES and human health. Viewing the relationship
      between soils and human health through the ES lens reveals that soil ES such as
      the provisioning of shelter, clothing, and fuel have been overlooked in the soil
      and human health literature. Shelter is important to human health because it
      provides protection against inclement weather, temperature extremes, and other
      potential threats. Clothing provides a more consistent micro-environment around
      the skin and also provides protection from ultraviolet radiation and some
      parasites. Fuel allows us to warm shelters, providing refuge from cold
      temperatures, and cook food, which reduces disease. The materials supplied by
      soils in support of these functions are often done so in a more environmentally
      responsible way than is the case with many modern building and clothing materials
      or with fossil fuels. However, it is important to realize that sustainable
      management practices are critical in order to achieve environmentally responsible
      production of these products. Future studies need to investigate the links
      between these overlooked soil ES and human health.

PMID- 30227284
TI  - Long-term analysis of fish assemblage structure in the middle section of the Sava
      River - The impact of pollution, flood protection and dam construction.
AB  - At the beginning of the 20th century, the middle section of the Sava River in
      Croatia was unaffected by major human activities and rich in ichthyofauna. The
      Sava River was important for commercial and recreational fishing for the local
      population, which still remains today. However, the 1920s mining industry was
      established in Slovenia, which emitted carbon dust into the Sava River. At the
      same time, the construction of embankments to mitigate flooding started in the
      middle section. Furthermore, in the 1980s, the Krsko nuclear power plant (NPP),
      and in the 2010s, the Krsko hydropower plant (HPP) were built in Slovenia. These
      activities could have an impact on the composition of fish communities downstream
      from the major sources of disturbances. Therefore, the main aim of this paper
      were to analyze the changes in fish assemblages of the Sava River from 1978 to
      2017, prior to and after the construction of Krsko NPP and HPP at the Medsave
      site on the Sava River, 20 km downstream from the major construction operations.
      Collected data were divided into four sampling periods (SP): SP1, from 1978 to
      1980; SP2, from 1991 to 1994; SP3, from 2001 to 2006, and SP4 from 2011 to 2017.
      Besides alien fish species, water quality and hydromorphological modifications
      were identified as significant stressors. In SP1 and SP2 limnophilic and
      eurytopic fish groups were predominant, and 26 different fish species were
      identified, but in SP3 and SP4 rheophilic fish groups become dominant, and the
      diversity has declined to 21 species. Threatened species blageon, Telestes
      souffia seems to be missing from the main course of the Sava River in last 20
      years. It can be concluded that disturbances in the fish assemblage pattern have
      coincided with the presence of multiple stressors of human origin.

PMID- 30227285
TI  - Traffic-related air emissions in Houston: Effects of light-rail transit.
AB  - Recent studies have suggested that automobile pollution poses significantly more
      harmful health impacts than previously realized. Light-rail transit (LRT) is a
      major type of transportation infrastructure, but there has been little research
      assessing the air quality effects of LRT based on the actual air pollution data.
      This study aimed to assess the effects of LRT on automobile-related air emissions
      in Houston. Specifically, we examined the effects of LRT on key tailpipe
      pollutants-carbon monoxide and acetylene-as well as other traffic pollution
      surrogates referred to as BTEX (benzene, toluene, ethylbenzene, and xylene),
      measured from ambient air monitoring stations. An interrupted time series design
      and analysis was used to determine the impact of an intervention, where the
      intervention was the opening of an LRT on January 1, 2004, with two years (2002
      2003) of before and two years (2004-2005) of after period data. We found that,
      after controlling for weather, the opening of the LRT was associated with
      statistically significant reductions in traffic-related air emissions.
      Specifically, at the exposure sites, the daily maximum carbon monoxide level was
      reduced roughly by 24%, and the daily level of toluene was reduced roughly by 60%
      (33% after accounting for the reduction at the comparison site). Our findings
      lend support to the air quality benefits of LRT by providing suggestive evidence
      of positive effects of LRT based on actual air pollution monitoring data. This
      study's findings also emphasize the importance of developing effective measures
      to assess traffic-related pollution and call for advanced data collection
      strategies of additional data, including traffic volume and speed data.

PMID- 30227286
TI  - Estimating microplastic-bound intake of hydrophobic organic chemicals by fish
      using measured desorption rates to artificial gut fluid.
AB  - One of the most important concerns about marine microplastics is their role in
      delivery of chemical contaminants to biota. The contribution of microplastic
      ingestion to the overall uptake of five hydrophobic organic chemicals (HOCs)
      [alpha-, beta-, and gamma-hexachlorocyclohexanes (HCHs), pentachlorobenzene
      (PeCB), and hexachlorobenzene (HeCB)] by fish is evaluated in this study.
      Partition coefficients of all five HOCs between surfactant micelles and simulated
      intestinal fluid (SIF), as well as between protein and SIF, were experimentally
      determined. Desorption of model HOCs from a polyethylene film into an artificial
      gut solution was measured to estimate the fraction of HOCs that can be absorbed
      from microplastics during their gut retention time. Monte-Carlo simulation (n =
      100,000) showed that the uptake via microplastic ingestion will be negligible for
      HCHs as compared to uptake via other exposure routes, water ventilation and food
      ingestion. On the other hand, microplastic ingestion might increase the total
      uptake rate of PeCB and HeCB due to their accelerated desorption from
      microplastics into the artificial gut solution under the model scenario, assuming
      an extremely high intake of microplastics. However, the steady-state
      bioaccumulation factor was predicted to decrease with increasing ingestion of
      microplastics, showing a dilution effect by microplastic ingestion. Results
      indicate that HOCs that are close to be at phase equilibrium between
      microplastics and environmental media are not likely to be further accumulated
      via ingestion of microplastics; this is true even for cases, where ingestion of
      microplastics contributes significantly to the total uptake of HOCs. Therefore,
      future studies need to focus on hydrophobic plastic additives that may exist in
      microplastics at a concentration higher than their equilibrium concentration with
      water.

PMID- 30227287
TI  - Weir building: A potential cost-effective method for reducing mercury leaching
      from abandoned mining tailings.
AB  - To mitigate mercury (Hg) pollution and reduce Hg downstream transportation, a
      weir was designed by a river system that had been inflicted by leachate from the
      slagheap of the Yanwuping Hg mine in Wanshan Hg mining area. A whole year
      monitoring of Hg species was conducted, and the efficiency of Hg reduction by the
      weir application was evaluated. The Hg concentrations in the river water were
      significantly higher in the wet season than in the dry season. Waterflow was
      confirmed to be the main driving factor for Hg mobilization and transportation,
      and an episode study revealed that most Hg was released in times of storms.
      Increased monitoring and preventive maintenance measures need to be taken on
      barriers in advance of storms. A large proportion of the total Hg (THg) and
      methylmercury (MeHg) is associated to particles. During the study period,
      approximately 412 g THg and 4.04 g total MeHg (TMeHg) were released from the YMM
      slagheap, of which 167 g THg and 1.15 g TMeHg were retained by the weir.
      Annually, 40.4% THg and 38.4% TMeHg was retained by the weir. Weir construction
      is considered as a potential cost-effective measure to mitigate Hg in river water
      and should be promoted and extended in the future after optimization.

PMID- 30227288
TI  - Computing structural and functional flow and sediment connectivity with a new
      aggregated index: A case study in a large Mediterranean catchment.
AB  - Hydrological connectivity in large catchments is influenced by natural and human
      induced heterogeneities and dynamic processes. In this study, a new aggregated
      index (AIC) based on topography, C-RUSLE factor, RUSLE2 rainfall erosivity,
      residual topography and soil permeability, was proposed to model structural and
      functional flow and sediment connectivity (FSC). It was tested in a large
      Mediterranean catchment (Vero River, NE Spain, 380 km2) with contrasted
      physiographic and climatic conditions (19 land uses and 15 types of lithology).
      Twelve weather stations were used and simulations were done at 5 m of pixel
      resolution using a LiDAR-derived DEM and the D-Infinity algorithm. Structural FSC
      (FSC-st) was computed with both an updated version of Borselli's index (IC) and
      the AIC. Values of connectivity with AIC followed a normal distribution with a
      wider range of values compared with the non-normal distribution obtained with
      Borselli's approach. The differences in the values of FSC-st between the
      different land uses were similar with the two indices and in agreement with the
      soil erosion rates reported in comparable landscapes. The spatial characteristics
      at sub-catchment scale were better reflected with AIC although values of FSC-st
      in the river and outlet were similar between both indices. Functional FSC (FSC
      fn) was computed with AIC during 96 months (September 2009-August 2017)
      characterising the spatio-temporal dynamic at catchment scale (18% of coefficient
      of variation). FSC-fn was higher in September, October, June and July and lower
      during the period December-February. Variation of connectivity in the stream was
      higher than in the hillslopes. Modelling testing with river flow was satisfactory
      between November and March, and during the months with high discharge values and
      weak during the summer, suggesting different runoff and sediment responses over
      the year. The new AIC appeared as a suitable tool for geomorphic and hydrological
      studies at catchment scale.

PMID- 30227289
TI  - Geochemical and mineralogical constraints in iron ore tailings limit soil
      formation for direct phytostabilization.
AB  - The present study aimed to characterize key physico-chemical and mineralogical
      attributes of magnetite iron (Fe) ore tailings to identify potential constraints
      limiting in situ soil formation and direct phytostabilization. Tailings of
      different age, together with undisturbed local native soils, were sampled from a
      magnetite mine in Western Australia. Tailings were extremely alkaline (pH > 9.0),
      with a lack of water stable aggregate and organic matter, and contained abundant
      primary minerals including mica (e.g., biotite), with low specific surface area
      (N2-BET around 1.2 m2 g-1). These conditions remained relatively unchanged after
      four years' aging under field conditions. Chemical extraction and spectroscopic
      analysis [e.g., X-ray diffraction (XRD) and synchrotron-based Fe K edge X-ray
      absorption fine structure spectroscopy (XAFS) analysis] revealed that the aging
      process decreased biotite-like minerals, but increased hematite and magnetite in
      the tailings. However, the aged tailings lacked goethite, a compound abundant in
      natural soils. Examination using backscattered-scanning electron microscope -
      energy dispersive X-ray spectrometry (BSE-SEM-EDS) revealed that aged tailings
      contained discrete sharp edged Fe-bearing minerals that did not physically
      integrate with other minerals (e.g., Si/Al bearing minerals). In contrast, Fe
      minerals in native soils appeared randomly distributed and closely amassed with
      Si/Al rich phyllosilicates, with highly eroded edges. The lack of labile organic
      matter and the persistence of alkaline-saline conditions may have significantly
      hindered the bioweathering of Fe-minerals and the biogenic formation of secondary
      Fe-minerals in tailings. However, there is signature that a native pioneer plant,
      Maireana brevifolia can facilitate the bioweathering of Fe-bearing minerals in
      tailings. We propose that eco-engineering inputs like organic carbon
      accumulation, together with the introduction of functional microbes and pioneer
      plants, should be adopted to accelerate bioweathering of Fe-bearing minerals as a
      priority for initiating in situ soil formation in the Fe ore tailings.

PMID- 30227290
TI  - Shiga toxin-producing Escherichia coli in wild ungulates.
AB  - Shiga toxin-producing Escherichia coli (STEC) are zoonotic pathogens that live in
      the gastrointestinal tract of wildlife and cattle without causing disease. In
      humans, their colonization and infection lead to life-threatening disease. We
      investigated the occurrence of STEC in wild ungulates (wild boar, red deer and
      roe deer) inhabiting areas differently impacted by anthropogenic activities. STEC
      were detected in 9% (n = 6) of the samples and were recovered from the three
      species: 1 of wild boar, 4 of red deer and 1 of roe deer. All the isolates (n =
      7) were non-O157 STEC encoding stx1 (n = 2; 29%) and/or stx2 genes (n = 6; 86%).
      O27:H30 was the most frequent serotype identified, followed by O146:H21 and
      O146:H28. Two STEC were O-untypable: ONT:H28 and ONT:H52. The phylo-groups
      identified were B1 (n = 3), E (n = 3) and F (n = 1). All the isolates recovered
      were susceptible to the different classes of antibiotics tested, although
      resistance genes were found in two strains. Apart from stx, all STEC encode many
      virulence factors (VF), particularly adhesins and/or other toxins. A strain with
      13 VF collected from roe deer has a high enterohemorrhagic risk due to the
      presence of intimin, hemolysin and protease effectors genes. Enterohemorrhagic E.
      coli (EHEC) are implicated in the major cases of human infection and mortality,
      highlighting the zoonotic potential of wildlife-associated STEC. Wild ungulates
      are reservoirs of STEC potentially pathogenic to humans. Therefore, following the
      One Health concept, it is crucial to establish worldwide local monitoring
      programs that will benefit human, animal and environmental health.

PMID- 30227291
TI  - Mortality and morbidity associated with ambient temperatures in Taiwan.
AB  - BACKGROUND: This study evaluated integrated risks of all-cause mortality,
      emergency room visits (ERVs), and outpatient visits associated with ambient
      temperature in all cities and counties of Taiwan. In addition, the modifying
      effects of socio-economic and environmental factors on temperature-health
      associations were also evaluated. METHODS: A distributed lag non-linear model was
      applied to estimate the cumulative relative risks (RRs) with confidence intervals
      of all-cause mortality, ERVs, and outpatient visits associated with extreme
      temperature events. Random-effect meta-analysis was used to estimate the pooled
      RR of all-cause mortality, ERVs, and outpatient visits influenced by socio
      economic and environmental factors. RESULTS: Temperature-related risks varied
      with study area and health outcome. Meta-analysis showed greater all-cause
      mortality risk occurred in low temperatures than in high temperatures. Integrated
      RR of all-cause mortality was 1.71 (95% confidence interval [CI]:1.43-2.04) in
      the 5th percentile temperature and 1.10 (95% CI: 1.05-1.15) in the 95th
      percentile temperature, while the lowest mortality risk was in the 60th
      percentile temperature (22.2  degrees C). Risk for ERVs increased when
      temperature increased (RR was 1.21 [95% CI: 1.17-1.26] in 95th percentile
      temperature), but risk of outpatient visits increased at low temperatures (RR was
      1.06 [95% CI: 1.01-1.12] in the 5th percentile temperature). Certain socio
      economic factors significantly modified low-temperature-related mortality risks,
      including number of employed populations, elders living alone from lower-income
      families, and public and medical services. CONCLUSIONS: This study found that
      mortality and outpatient visits were higher at low temperature, while ERVs risk
      was higher at high temperature. Future plans for public health and emerging
      medical services responding to extreme temperatures should consider regional and
      integrated evaluations of temperature-related health risks and modifying factors.

PMID- 30227292
TI  - Temporal variation and spatial scale dependency of the trade-offs and synergies
      among multiple ecosystem services in the Taihu Lake Basin of China.
AB  - Grasping the temporal-spatial characteristics of interactions and spatial scales
      of multiple ecosystem services is the foundation for sustainable ecosystem
      management. Eight ecosystem services, including crop production, freshwater
      supply, aquatic production, net primary production, soil conservation, water
      retention, flood regulation, and forest recreation were measured at the 1-km2
      pixel scale in the Taihu Lake Basin (TLB) of China from 1990 to 2010.
      Furthermore, we quantified the trade-offs and synergies of services at different
      periods of urbanization and across the 1-km2 pixel scale and the county scale. We
      aim to find which ecosystem services interactions temporally vary and depend on
      spatial scale. Our results found that: 1). Tremendous amount of cultivated lands
      were converted to construction land, and rapidly shrank from 1990 to 2010. 2).
      Determined by land use, different ecosystem services had spatial heterogeneity of
      their strength. Ecosystem services hot spots experienced an increasing trend
      while cold spots showed a trend of decreasing first and then increasing from 1990
      to 2010. 3). Trade-offs between provisioning services and regulating services at
      the 1-km2 pixel scale changed over time. There was a new synergy between
      freshwater supply and aquatic production at the 1-km2 pixel scale in 2010 with
      the human demand. 4). From 1990 to 2010, the changes of provisioning services led
      to trade-offs among provisioning services, regulating services and cultural
      services at two scales. Taking temporal variation and scale dependence into
      account, this research is helpful to the delineation of "Ecological Conservation
      Redline" and implement the project of "Grain for Green". We also provide
      suggestions for maintaining ecosystem services with economic growth in China's
      Yangtze River Economic Belt for land use policies and decision making.

PMID- 30227293
TI  - Improved methane production and energy recovery of post-hydrothermal liquefaction
      waste water via integration of zeolite adsorption and anaerobic digestion.
AB  - Hydrothermal liquefaction (HTL) is a promising technology for converting organic
      wastes into bio-crude oil, with organic-rich post-hydrothermal liquefaction
      wastewater (PHWW) as by-product. In this study, zeolite adsorption and anaerobic
      digestion (AD) were integrated to improve the methane production and energy
      recovery of PHWW from Chlorella 1067. A statistical design for maximum toxicants
      removal by zeolite was applied before AD process. Zeolite could mitigate the
      inhibition associated to compounds such as ammonia, N-heterocyclic compounds,
      etc. in PHWW and thereby shortening the lag phase and increasing methane
      production by 32-117% compared with that without zeolite adsorption. Zeolite
      adsorption also increased energy recovery efficiency (up to 70.5%) for this
      integrated system. Integration of HTL and AD brought higher energetic return from
      feedstock via oil and biomethane production, which may offer insight into
      industrial application of microalgae biomass in the circular economy. In
      addition, carbon and nitrogen flow for the integrated process was determined.

PMID- 30227294
TI  - Biological As(III) oxidation in biofilters by using native groundwater
      microorganisms.
AB  - Arsenic (As) contamination in drinking water represents a worldwide threat to
      human health. During last decades, the exploitation of microbial As
      transformations has been proposed for bioremediation applications. Among
      biological methods for As-contaminated water treatment, microbial As(III)
      oxidation is one of the most promising approaches since it can be coupled to
      commonly used adsorption removal technologies, without requiring the addition of
      chemicals and producing toxic by-products. Despite the As(III) oxidation
      capability has been described in several bacterial pure or enrichment cultures,
      very little is known about the real potentialities of this process when mixed
      microbial communities, naturally occurring in As contaminated waters, are used.
      This study highlighted the contribution of native groundwater bacteria to As(III)
      oxidation in biofilters, under conditions suitable for a household-scale
      treatment system. This work elucidated the influence of a variety of experimental
      conditions (i.e., various filling materials, flow rates, As(III) inflow
      concentration, As(III):As(V) ratio, filter volumes) on the microbially-mediated
      As(III)-oxidation process in terms of oxidation efficiency and rate. The highest
      oxidation efficiencies (up to 90% in 3 h) were found on coarse sand biofilters
      treating total initial As concentration of 100 MUg L-1. The detailed microbial
      characterization of the As(III) oxidizing biofilms revealed the occurrence of
      several OTUs affiliated with families known to oxidize As(III) (e.g.,
      Burkholderiaceae, Comamonadaceae, Rhodobacteraceae, Xanthomonadaceae).
      Furthermore, As-related functional genes increased in biofilter systems in line
      with the observed oxidative performances.

PMID- 30227295
TI  - How is stereotactic brain biopsy evolving? A multicentric analysis of a series of
      421 cases treated in Rome over the last sixteen years.
AB  - OBJECTIVE: In recent decades, frame-based (FBB) and frame-less stereotactic brain
      biopsy (FLB) have played a crucial role in defining the diagnosis and management
      of expanding intracranial lesions in critical areas. During the same period,
      there have been significant advances in diagnostic imaging, a shift in surgical
      strategies towards extensive resection in gliomas and new molecular
      classification of brain tumors. Taking these advances into account, we have
      evaluated whether significant changes have occurred over the last sixteen years
      of our clinical practice in terms of frequency, indications, target selection,
      and the histologic results of stereotactic brain biopsy (SBB) procedures.
      PATIENTS AND METHODS: We analyzed a series of 421 SBB cases treated between
      January 2002 and June 2017 in three major neurosurgical institutes in Rome,
      serving a total of 1.5 million people. Within this series, 94.8% of patients
      underwent FBB, while, more recently, FLB was performed in 5.2% of cases. The
      entire period under consideration, running from 2002 to 2017, has been further
      stratified into four-year time-frames (2002-2005, 2006-2009, 2010-2013, 2014
      2017) for the purpose of analysis. RESULTS: The diagnostic yield was 97%. Final
      diagnoses revealed tumors in 90% of cases and non-neoplastic masses in 7%, while
      3% of cases were not conclusive. The morbidity rate was 3% (12 cases) and
      mortality was 0.7% (3 cases). Intra-operative frozen sections were made in 78% of
      biopsies. In our three institutes, the number of SBBs decreased steadily
      throughout the time-frames under consideration. We have also observed a
      statistically significant reduction in biopsy procedures in lobar lesions, while
      those performed on the basal ganglia increased and the number of SBBs of multiple
      masses and lesions of the corpus callosum remained stable. Primary central
      nervous system diagnosis of lymphomas (PCNSL) was the sole diagnosis whose
      incidence increased significantly. CONCLUSIONS: Over the last sixteen years, we
      have witnessed a significant decrease in SBB procedures and a modification in
      target selection and histologic results. Despite the significant evolution of
      neuroimaging, an accurate non-invasive diagnosis of intracranial expanding
      lesions has not yet been achieved. Furthermore, the most recent WHO
      classification of brain tumors (2016), which incorporates molecular and
      morphological features, has boosted the need for molecular processing of tissue
      samples in all expanding brain lesions. For these reasons, it is likely that SBBs
      will continue to be performed in specific cases, playing a significant role in
      diagnostic confirmation by providing tissue samples, so as to better assess the
      biology and the prognosis of cerebral lesions, as well as their sensitivity to
      standard radio-chemotherapy or to new molecular target therapies.

PMID- 30227296
TI  - Trends in the application of Bacillus in fermented foods.
AB  - Bacillus species such as Bacillus subtilis and Bacillus amyloliquefaciens are
      widely used to produce fermented foods from soybeans and locust beans in Asian
      and West African countries, respectively. Genomic information for B. subtilis
      strains isolated from Asian Bacillus-fermented foods (BFFs) has been gathered,
      and the chemical components of fermented products were defined with metabolomic
      approaches, facilitating the development of new starter strains and the
      evaluation of health claims. On the other hand, although advanced studies have
      been performed for some commercially produced BFFs, home-manufactured products
      still remain to be characterized in rural areas. In West Africa, the microbial
      flora of BFFs was examined in detail, leading to the isolation of candidates of
      the starter that produced bacteriocin against Bacillus cereus contaminating the
      products. These studies may provide a choice of Bacillus strains in food
      application and increase opportunities for further usage of Bacillus in foods.

PMID- 30227297
TI  - An improved iterative wave function reconstruction algorithm in high-resolution
      transmission electron microscopy.
AB  - Exit wavefunction reconstruction is a powerful image processing technique to
      enhance the resolution and the signal-to-noise ratio for atomic-resolution
      imaging in both aberration uncorrected and corrected transmission electron
      microscopes. The present study aims to improve the performance of the iterative
      wavefunction reconstruction algorithm in comparison not only with its
      conventional form but also with the popular commercial Trueimage software for
      exit wavefunction reconstruction. It is shown that by implementing a wave
      propagation procedure for refining its image alignment, the iterative
      wavefunction reconstruction algorithm can be greatly improved in accurately
      retrieving the wavefunctions while keeping its original advantages, which allow
      the reconstruction be performed with less images and a larger defocus step in the
      data set of through-focus image series. In addition, calculations of this
      algorithm can be accelerated drastically by the graphic processing unit (GPU)
      hardware programming using the popular computer unified device architecture
      language, whose computing speed can be 25-38 times as fast as a central
      processing unit (CPU) program.

PMID- 30227298
TI  - A novel PHOX2B gene mutation in an extremely low birth weight infant with
      congenital central hypoventilation syndrome and variant Hirschsprung's disease.
AB  - Congenital central hypoventilation syndrome is a disorder of respiratory control
      caused by mutations in the paired-like homeobox 2B gene. Mutations in the paired
      like homeobox 2B gene are also responsible for Hirschsprung's disease. Variant
      Hirschsprung's disease is a rarer disorder that does not meet the diagnostic
      criteria of Hirschsprung's disease, although severe functional bowel obstruction
      persists. We present a case of an extremely low birth weight infant with
      congenital central hypoventilation syndrome and variant Hirschsprung's disease. A
      male infant who was diagnosed to have fetal growth restriction and polyhydramnios
      was delivered by emergency cesarean section at 30 weeks and 3 days of gestational
      age due to non-reassuring fetal status. The birth weight was 979 g, and intensive
      care was started immediately following delivery. The patient exhibited refractory
      apnea and was diagnosed with congenital central hypoventilation syndrome by
      genetic testing of the paired-like homeobox 2B gene. The patient also exhibited
      refractory functional bowel obstruction and was diagnosed to have variant
      Hirschsprung's disease through pathological examination of his intestinal
      specimens. The patient grew slowly but surely with intensive care including
      mechanical ventilation and parenteral nutrition. However, the patient repeatedly
      suffered from sepsis and died of fungemia at 197 days of age. This is the first
      congenital central hypoventilation syndrome case that was accompanied with
      variant Hirschsprung's disease, and the paired-like homeobox 2B mutation detected
      in this case (NM_003924.3: c.441G > C; p.(Gln147His)) is novel. This case
      suggests that the paired-like homeobox 2B mutation causes not only congenital
      central hypoventilation syndrome and Hirschsprung's disease, but also variant
      Hirschsprung's disease in humans. It also highlights the extreme difficulty in
      treating premature infants with severe and prolonged functional bowel
      obstruction.

PMID- 30227299
TI  - Tumor-associated macrophages in breast cancer: Innocent bystander or important
      player?
AB  - Tumor-associated macrophages (TAMs) are important tumor-promoting cells in the
      breast tumor microenvironment. Preclinically TAMs stimulate breast tumor
      progression, including tumor cell growth, invasion and metastasis. TAMs also
      induce resistance to multiple types of treatment in breast cancer models. The
      underlying mechanisms include: induction and maintenance of tumor-promoting
      phenotype in TAMs, inhibition of CD8+ T cell function, degradation of
      extracellular matrix, stimulation of angiogenesis and inhibition of phagocytosis.
      Several studies reported that high TAM infiltration of breast tumors is
      correlated with a worse patient prognosis. Based on these findings, macrophage
      targeted treatment strategies have been developed and are currently being
      evaluated in clinical breast cancer trials. These strategies include: inhibition
      of macrophage recruitment, repolarization of TAMs to an antitumor phenotype, and
      enhancement of macrophage-mediated tumor cell killing or phagocytosis. This
      review summarizes the functional aspects of TAMs and the rationale and current
      evidence for TAMs as a therapeutic target in breast cancer.

PMID- 30227300
TI  - Effects of zinc pyrithione on biochemical parameters of the freshwater Asian clam
      Corbicula fluminea.
AB  - Zinc pyrithione (ZnPT) is an organometallic biocide with bactericide, algaecide,
      and fungicide activity. Considering this biological activity, ZnPT has been used
      in anti-fouling paints, and also in human therapeutics and cosmetics, in shampoos
      to treat dandruff and seborrhoea. Despite its potential uses and consequent
      presence in the aquatic environment, the ecotoxicological effects of ZnPT are
      poorly understood. This work aims to characterise the effects of ZnPT in
      biochemical parameters of the Asian clam, one of the most invasive bivalves known
      for its biofouling action in hydro-dependent industries, using a classical (LC50
      determination) and a biomarker-based approach (quantification of the activities
      of catalase, GSTs, and acetylcholinesterase, and also the muscle glycogen
      content). The here determined LC50-96 h for zinc pyrithione was 2.17 mg/L. ZnPT
      caused significant increases in the activity of catalase and of cholinesterases.
      These findings evidence the pro-oxidative effects caused by the metabolism of
      ZnPT. Despite the absence of clear effects, it is important to stress that the
      presence of ZnPT in the wild is usually accompanied by other pyrithiones, whose
      co-existence can contribute to the exertion of considerable toxic effects.

PMID- 30227301
TI  - Effect of glutathione on sperm quality after short-term cryopreservation in
      seurukan fish Osteochilus vittatus (Cyprinidae).
AB  - The objective of this present study is to determine the optimum concentration for
      glutathione in the cryopreservation of seurukan fish (Osteochilus vittatus)
      spermatozoa. A completely randomized design (CRD) was used with 6 treatments and
      3 replications. The Seurukan fish sperm was diluted in extender with a ratio of
      1:20 (sperm: extender), then glutathione was added at a concentration of 0, 10,
      20, 30, 40 and 50  mg L-1. Next, the sperm thawed at 39-40  degrees C for 3 min
      and mixed with 100 eggs which were randomly selected. The success of the
      fertilized egg was observed 6 h after fertilization, while the hatching rate was
      examined 60 h after fertilization. The ANOVA test showed that the addition of
      glutathione significant affected the sperms motility, fertility and hatching rate
      of seurukan fish Osteochilus vittatus eggs (P < 0.05). By segregation the fresh
      sperm, a higher sperm motility rate was recorded with an addition of 30 mgL-1 of
      glutathione (63.00 +/- 5.89), however, this value was not significantly different
      from using concentration of 10 and 20  mg L-1. A higher fertilization rate was
      produced using glutathione concentration of 50  mg L-1 (51.33 +/- 17.01);
      however, it was also not significantly different from the concentration of 20, 30
      and 40 mgL-1. In addition, a higher hatching rate was also recorded using
      glutathione concentration of 50 mg L-1 (40.33 +/- 12.89), this value was not
      significantly different from using 40 mgL-1 glutathione. Hence, a conclusion was
      drawn that the optimum concentration of glutathione is 40 mg L-1 of diluent.

PMID- 30227302
TI  - Scopolamine for uterine involution of dairy cows.
AB  - The objective of this study was to evaluate the effect of administration of
      scopolamine (a parasympatholytic drug) immediately after delivery, on uterine
      involution in dairy cows. The cows were divided into two groups: group T (treated
      with scopolamine butylbromide 40 mg/100 kg P.V., within 24 h of delivery) and
      group C (treated with 2 ml/q of saline solution). The cows were monitored at T0,
      within 24 h of delivery, T7, T14, T28 and T40 respectively 7th, 14th, 28th and
      40th day postpartum, by measuring the levels of hydroxyproline (HYP), an
      important marker of uterine involution; by ultrasound examination for the
      measurement of the diameter of uterine horns and of blood flow in the middle
      uterine artery; and by evaluation of reproductive indices. HYP showed higher
      concentrations in the T group than in the C group at all times, but the
      difference was significant at T7 and T40. Uterine diameters were reduced from T7
      to T40, with lower values in the T group, as compared to the C group; the
      pulsatility index (PI) of the middle uterine artery increased in the T group
      compared to the C group, with a statistically significant difference at T7. There
      was a better conception-delivery interval and higher pregnancy rate in the T
      group compared to the C group. It is likely that scopolamine blocked the uterine
      contractions in postpartum, for the duration of its half-life. After cessation of
      its pharmacological effect, the uterus may have started to contract more
      effectively. These results suggested that scopolamine could be useful as a
      pharmacological approach to postpartum management.

PMID- 30227303
TI  - Effects of live yeast dietary supplementation on hormonal profile, ovarian
      follicular dynamics, and reproductive performance in dairy cows exposed to high
      ambient temperature.
AB  - Two experiments were conducted to investigate the effects of dietary
      supplementation with live yeast culture on hormonal profile, ovarian follicular
      dynamics and reproductive performance of lactating dairy cows exposed to high
      ambient temperature. In Expt. 1, Holstein cows were fed a diet with (n = 6) or
      without (n = 6) 4 g yeast/h/d from 21 d before expected calving date until 8
      weeks postpartum. Concentrations of glucose, insulin, insulin like growth factor
      I (IGF-I), estradiol-17beta (E-17beta) and progesterone (P4) were determined in
      plasma, and transrectal ultrasonography was used to monitor ovarian follicular
      dynamics. In Expt. 2, 150 Holstein cows (75/dietary group) received same diets as
      Expt. 1 with the exception that diets were fed from d 1 to d 70 postpartum. The
      effect of dietary treatments on reproductive performance was examined. In Expt.
      1, plasma IGF concentrations during dietary treatment were higher (P = 0.05) in
      cows fed diets supplemented with yeast. On d 60 postpartum, average plasma
      concentrations of glucose (48.3 vs. 41.0 mg/dL) and insulin (0.90 vs. 0.23
      MUU/mL), were also greater in cows fed diets supplemented with yeast compared to
      that in cow fed diets without supplementation. Similarly, plasma concentrations
      of E-17beta at estrus (P = 0.016) and P4 on d 10 of the estrous cycle (P = 0.021)
      were greater in yeast-supplemented cows. Moreover, yeast supplementation resulted
      on average in an estrous cycle 2.6 d shorter (P = 0.05) and in the development of
      larger ovulatory follicles (18.4 vs. 17.2 mm in diameter; P < 0.01). In Expt. 2,
      days open were fewer and the proportion of pregnant cows at 120 and 150 d
      postpartum were greater (P < 0.01) in cows fed diets supplemented with yeast
      compared to those receiving diets without yeast. In summary, cows fed diets
      supplemented with yeast had greater plasma IGF-I, E-17beta and P4 concentrations,
      larger ovulatory follicles, shorter estrous cycles, and improved reproductive
      performance. Therefore, live yeast dietary supplementation could enhance
      lactating dairy cow's fertility during heat stress through improvement in
      hormonal profile and development of larger ovulatory follicles.

PMID- 30227304
TI  - Sirtuin3 (SIRT3) gene molecular characterization and SNP detection in prolific
      and low prolific goat breeds.
AB  - Sirtuin3 (SIRT3) is a member of the Sirtuin family of NAD+-dependent deacetylase.
      They have evolved as a vital protein in preventing the activation of reactive
      oxygen species (ROS) in oocytes. A novel study on caprine SIRT3 was conducted, to
      characterize caprine SIRT3, to detect potential polymorphisms in SIRT3 and to
      analyze their association with litter size in the two indigenous goat breeds of
      India viz., the prolific Malabari and low prolific Attappady Black goats. A 1070
      bp mRNA sequence of SIRT3 cDNA comprised of an ORF of 1002 bp encoding 333 amino
      acids, having 96% identity with bovine SIRT3. The genomic DNAs from the goats (n
      = 222) were subjected to PCR and single strand conformation polymorphism (SSCP)
      of exon 5 fragment (213 bp) of caprine SIRT3. On analysis, two genotypes viz., DD
      and DE were observed with frequencies of 0.63 and 0.37 respectively. Further
      sequencing of the PCR products of the respective genotypes revealed a novel
      synonymous SNP (MF176159:c.691C > T). Genotypes of this fragment had a
      significant influence on number of kids born (P < 0.05) with DD genotype being
      superior to DE genotype. These results highlight the role of SIRT3 in
      reproduction traits and the detected novel SNP would aid in the Marker Assisted
      Selection programmes and thus SIRT3 can considered as a potential candidate gene
      for reproduction traits in goats.

PMID- 30227305
TI  - Analysis of Genomic Alteration in Primary Central Nervous System Lymphoma and the
      Expression of Some Related Genes.
AB  - Primary central nervous system lymphoma (PCNSL) is a rare and special type of non
      Hodgkin lymphoma. The treatment of PCNSL is comprehensive, combining surgery,
      radiotherapy, and chemotherapy. However, the outcome is poor because of its high
      invasiveness and rate of recurrence. We analyzed 22 cases of PCNSL using next
      generation sequencing (NGS) to detect 64 candidate genes. We used
      immunohistochemical methods to analyze gene expression in 57 PCNSL samples. NGS
      showed that recurrent mutations in KMT2D and CD79B, components of the NF-kappaB
      pathway, accounted for 65% of total mutations in PCNSL samples. The most frequent
      mutated gene was PIM1 (77.27%, 17/22), followed by MYD88 (63.64%, 14/22), CD79B
      (69.09%, 13/22), and KMT2D (50.00%, 11/22). Mutations of the CD79B gene were
      associated with an inferior progression-free survival (PFS), and GNA13 gene
      mutations were associated with a shorter PFS and overall survival (OS) in PCNSL
      patients (P < .05). PIM1 and MYD88 were highly expressed in PCNSL patients and
      were related to their OS time. MYD88 overexpression might be an independent and
      poor prognostic predictor of OS time. In summary, we identified highly recurrent
      genetic lesions in CD79B and KMT2D, components of the NF-kappaB pathway, in PCNSL
      and validated the expression of PIM1 and MYD88 related to poor survival, thereby
      providing novel insights into the pathogenesis and precision medicine of PCNSL.

PMID- 30227306
TI  - Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative
      Cervical Adenocarcinoma via Regulation of Claudin-1 Expression.
AB  - Cervical adenocarcinomas are believed to lose estrogen response on the basis of
      no expression of a nuclear estrogen receptor such as ERalpha in clinical
      pathology. Here, we demonstrated that cervical adenocarcinoma cells respond to a
      physiological concentration of estrogen to upregulate claudin-1, a cell surface
      molecule highly expressed in cervical adenocarcinomas. Knockout of claudin-1
      induced apoptosis and significantly inhibited proliferation, migration, and
      invasion of cervical adenocarcinoma cells and tumorigenicity in vivo.
      Importantly, all of the cervical adenocarcinoma cell lines examined expressed a
      membrane-bound type estrogen receptor, G protein-coupled receptor 30
      (GPR30/GPER1), but not ERalpha. Estrogen-dependent induction of claudin-1
      expression was mediated by GPR30 via ERK and/or Akt signaling. In surgical
      specimens, there was a positive correlation between claudin-1 expression and
      GPR30 expression. Double high expression of claudin-1 and GPR30 predicts poor
      prognosis in patients with cervical adenocarcinomas. Mechanism-based targeting of
      estrogen/GPR30 signaling and claudin-1 may be effective for cervical
      adenocarcinoma therapy.

PMID- 30227307
TI  - Use of by-products from integrated steel plants as catalysts for the removal of
      trichloroethylene from groundwater.
AB  - The removal of tricholoroethylene (TCE) has been investigated in this work
      through the Fenton-like process using different catalytic materials obtained from
      metallic by-products of the steel industry. These materials are the slag produced
      during the transformation of molten pig iron produced in a blast furnace into
      liquid steel (SLD), the dry particles (or dust) obtained from the bag filters
      installed in the coking installations to minimize diffuse emissions (POCA) and
      the dry particles obtained from the liquid sludge from the scrubber (LHA). This
      study aims to explore the potential of these materials for being used as
      permeable catalytic barriers to treat groundwater polluted with trichloroethylene
      (TCE). The wastes used as catalysts were chemically and physically characterized
      to determine their composition and porosity. The results of this study point out
      that among the different catalysts used LHA showed the highest catalytic activity
      to degrade TCE using hydrogen peroxide. Moreover, LHA was the most efficient
      catalyst using hydrogen peroxide due to its higher stoichiometric efficiency. It
      is thus concluded that LHA has a high potential to be combined with hydrogen
      peroxide in permeable catalytic barriers to remove organic compounds from
      groundwater.

PMID- 30227308
TI  - Impacts of ammonia nitrogen on autothermal thermophilic micro-aerobic digestion
      for sewage sludge treatment.
AB  - The concentration of ammonia nitrogen is relatively high during autothermal
      thermophilic micro-aerobic digestion (ATMAD), which could significantly affect
      the sludge stabilization. This paper aims to investigate the impacts of ammonia
      nitrogen on ATMAD process, batch experiments were carried out with dosage of
      certain amount of NH4HCO3 into digestion system. The total ammonia nitrogen (TAN)
      was considered as a suitable indicator to characterize the ammonia inhibition. As
      the TAN reached to approximately 1000 mg L-1, the sludge digester presented a
      relatively low removal of volatile solids, due to adverse effects of ammonia
      nitrogen on sludge digestion. Three pathways that closely related to ammonia
      inhibition were investigated in this research. Digestion system could be
      inhibited by high TAN due to K+ deficiency of the cells and the decline of Mg2+
      in the cytoplasm, and the accumulations of reactive oxygen species lead to
      oxidative stress for the microbes. Ammonia inhibition can be mitigated by the
      increase of oxidative enzyme.

PMID- 30227309
TI  - Modeling arsenic (V) removal from water by micellar enhanced ultrafiltration in
      the presence of competing anions.
AB  - With increasing arsenic (As) contamination incidents reported around the world,
      better processes for As removal from industrial wastewater and other contaminated
      waters are required to protect drinking water sources. Complexation of As with
      cetylpyridinium chloride (CPC) cationic surfactant micelles, coupled with
      ultrafiltration (UF), has the potential to improve As removal, but competition
      from other anions could be a limiting factor. Using a binary-system ion-exchange
      model, the selectivity coefficients for binding of the monovalent and divalent
      forms of arsenate (As (V)) to cationic cetylpyridinium (CP+) micelles, relative
      to Cl-, were determined to be 0.55 for H2AsO4- and 0.047 mol L-1 for HAsO42-,
      respectively. The affinity sequence for binding of commonly occurring monovalent
      anions by CP+ micelles was found to be NO3- > Cl- > HCO3- > H2AsO4-, and for
      divalent anions, SO42- > HAsO42-. Distribution of As (V) between the micellar and
      aqueous phases was explored using ion exchange isotherms, with higher pH and
      lower concentrations of competing anions increasing rejection of As (V) across UF
      membranes. A model accounting for these effects, based on mass balances across UF
      membranes and selectivity coefficients for binding of anions to the CP+ micelles,
      was used to predict As (V) removal during micellar-enhanced ultrafiltration
      (MEUF) of mixtures of competing anions. Model predictions agreed well with
      experiment results for both artificial and spiked natural river water samples.
      Arsenic (~0.1 mM) removals of 91% and 84% were achieved from artificial waters
      and spiked natural river waters, respectively, by adding 20 mM CPC prior to UF.

PMID- 30227310
TI  - Diagnostic power of VEGF, MMP-9 and TIMP-1 in patients with breast cancer. A
      multivariate statistical analysis with ROC curve.
AB  - PURPOSE: Vascular endothelial growth factor is an important factor in promoting
      angiogenesis in malignant processes, matrix metalloproteinase-9 in the
      degradation of extracellular matrix, which enhances metastasis, and tissue
      inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to
      investigate the diagnostic power of these parameters in comparison to CA15-3 in
      breast cancer patients and in relation to the control group. MATERIALS/METHODS:
      The study included 120 breast cancer patients, 60 patients with benign breast
      tumors and 60 healthy women. Plasma levels of tested parameters were determined
      by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle
      immuno assay. RESULTS: Tissue inhibitor of metalloproteinase-1 showed the highest
      value of sensitivity in breast cancer group (86.25%) and, more importantly,
      highest value in breast cancer stage I (85%). Vascular endothelial growth factor
      also showed high sensitivity (stage I and II-75%, III-85%, IV-70% and 76.25% in
      total breast cancer group) and the highest specificity (85%) from all tested
      parameters. It was also the only parameter which had statistically significant
      area under curve in all stages. In the total breast cancer group all tested
      parameters showed statistically significant area under curve, but the maximum
      range was obtained for combination: 'vascular endothelial growth factor + CA15
      3'. Vascular endothelial growth factor seems to be the best candidate for
      diagnosing breast cancer stage I and for differentiating between breast cancer
      and non-carcinoma cases. CONCLUSIONS: The combined analysis of tested parameters
      and CA15-3 resulted in an increase in sensitivity and area under curve values,
      which provides hope for developing new panel of biomarkers that may be used in
      diagnosing breast cancer in the future.

PMID- 30227311
TI  - Clinical utility of anti-MOG antibody testing in a Danish cohort.
AB  - BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) can be
      found in different immune-mediated inflammatory CNS disorders. The full range of
      clinical manifestations may not have been fully discovered yet. METHODS: In a
      cross-sectional study 184 adults (age >= 16) were tested for anti-MOG antibody
      (Ab) with a cell-based assay. To define the relevant target population for anti
      MOG antibody testing in a neurology clinic, we divided the entire study
      population based on the presenting symptoms and classified cases followed for
      multiple sclerosis (MS) according to the clinical features and response to
      disease-modifying therapy. RESULTS: We identified eight (4.4%) MOG-Ab positive
      cases in the whole cohort. All eight cases had first manifestations suggestive of
      neuromyelitis optica spectrum disorder (NMOSD), but had highly variable disease
      courses and responses to therapy. This included a patient with chronic relapsing
      inflammatory optic neuropathy (CRION) responding only to therapy with infliximab.
      Four (3%) out of 134 cases followed for MS who tested positive for anti-MOG Ab
      showed atypical features and had poor response to therapy. CONCLUSION: A broad
      range of clinical and radiological features of anti-MOG associated disorder was
      observed in a single centre. MOG-Ab testing should be considered in patients with
      an NMOSD phenotype and in MS patients presenting atypical features. The potential
      use of infliximab therapy for MOG-Ab disease should be further investigated.

PMID- 30227312
TI  - Herpes simplex virus encephalitis temporally associated with dimethyl fumarate
      induced lymphopenia in a multiple sclerosis patient.
AB  - BACKGROUND: Dimethyl fumarate (DMF) is approved as first line therapy for
      relapsing-remitting multiple sclerosis (RRMS). In some (3%) patients, DMF induces
      a marked lymphopenia. Herpes simplex encephalitis (HSE) may occur in lymphopenic
      subjects under treatment with immune-suppressive drugs. CASE PRESENTATION: We
      report a case of a 39-year-old female patient with RRMS that developed HSE
      temporally associated with a marked and sudden drop in lymphocyte count, from
      1200/ul to 600/ul, in the peripheral blood. HSE DNA was demonstrated in the
      cerebrospinal fluid. HSE had the features that characterize HSE occurring in
      immunosuppressed subjects, i.e. less prominent CSF pleocytosis, bilateral and
      mainly cortical involvement and less extensive tissue necrosis. Antiviral therapy
      determined a progressive, although incomplete, improvement. Three months later
      the patient presented only a mild short-term memory deficit and sporadic episodes
      of inappropriate emotionality. Lymphocyte count returned to normal values
      (1120/ul) after DMF discontinuation. CONCLUSION: Our case of HSE in a lymphopenic
      DMF-treated RRMS patient, points out the necessity of further studies on DMF
      related lymphopenia, especially whether it implies an impaired immunity against
      viruses.

PMID- 30227313
TI  - Differential effects of cue-based and sequence knowledge-based predictability on
      multitasking performance.
AB  - Everyday multitasking often is characterized by predictable sequences. While such
      sequential regularities are present in setups using the Serial Reaction Time Task
      (SRTT), many laboratory studies on dual-tasking performance use random sequences
      of stimuli in either of the two tasks. In the current study, following single
      task training on the SRTT, participants completed trials where they were
      confronted with an additional visual-manual task with either a random (Experiment
      1) or a partially predictable (Experiment 2) stimulus sequence. In the SRTT, we
      cued participants with respect to which of the four stimulus options were yet to
      occur (before a new round with all four options would start). We randomly mixed a
      sequence to be practiced with random sequences of the same length and with the
      same constraint. Thus, we were able to vary predictability of upcoming stimuli
      (from chance to 100%) as well as sequence knowledge (practiced vs. random
      sequence) in order to assess how cueing and sequence knowledge, as two potential
      bases of prediction, would affect performance in single- and dual-tasking.
      Results suggest that both cueing and sequence knowledge-based prediction can lead
      to shorter RTs in dual-tasking. In previous studies, the disruption of sequence
      learning by adding a task with a random stimulus sequence has been linked to the
      effects of automatic prediction between events in the two tasks. In line with
      these studies, dual-task performance did not impede usage of sequence knowledge
      when a task with a predictable (rather than random) sequence of stimuli was added
      to the SRTT.

PMID- 30227315
TI  - Similar profiles of cognitive domain deficits between medication-naive patients
      with bipolar II depression and those with major depressive disorder.
AB  - BACKGROUND: Bipolar disorder (BD) II is more likely to be misdiagnosed as major
      depressive disorder (MDD) than other types of BD, leading to incorrect treatment
      and poor outcomes. Previous studies have shown inconsistent results regarding the
      differences in cognitive deficits between the two disorders. To eliminate the
      compounding effects of medication and aging, we sought to investigate changes in
      cognitive function in medication-naive, non-late-life patients with BDII and MDD.
      METHODS: Three subject groups were enrolled: 30 depressed BDII patients, 30
      depressed MDD patients and 30 healthy controls. All subjects underwent a battery
      of cognitive tests to assess 8 cognitive domains. The cognitive domains were
      compared between the three subject groups. In BDII and MDD, the effect sizes were
      computed as evaluation parameters, weighing the degree of the cognitive deficits
      and the correlations between cognitive test deficits and clinical variables were
      also computed. RESULTS: Compared with the controls, the BDII and MDD patients
      were characterized by similar deficits in psychomotor speed, working memory,
      visual memory, attention switching and verbal fluency. Moderate to severe
      deficits in the majority of cognitive tests were observed in the BDII and MDD
      patients. Furthermore, correlations between the modified Wisconsin Card Sorting
      Test total errors and age of onset in the BDII patients and between correct digit
      span responses (backward and total) and depressive severity were found in the MDD
      patients. CONCLUSIONS: Our findings suggest that BDII and MDD patients may suffer
      from similar profiles of cognitive domain deficits that may not assist in
      distinguishing between the two disorders. In addition, cognitive deficits may be
      correlated with the age of onset and depressive severity in mood disorders.

PMID- 30227314
TI  - Clinical and laboratory diagnosis of autoimmune factor V inhibitors: A single
      institutional experience.
AB  - BACKGROUND: Coagulation factor V inhibitors (FV-i) may occur in patients with
      congenital FV deficiency or previously hemostatically normal patients (autoimmune
      (AI)-FV-i). Most of the published literature is confined to case reports.
      OBJECTIVE: Describe clinical and laboratory features of AI-FV-i identified
      through the Special Coagulation Laboratory at Mayo Clinic, Rochester, Minnesota.
      METHODS: In this retrospective study individuals with FV-i screens performed from
      January 1999 to February 2017 were identified through the special coagulation
      laboratory database. Clinical presentation, management, and outcomes were
      collected for our institutional patients while detailed laboratory data was
      collected for all tested patients. RESULTS: Of patients with FV-i managed at our
      institution, 2/8 (25%) patients experienced no bleeding. There was no correlation
      between inhibitor titers and/or FV activity (FV:C) levels and clinical bleeding.
      Hemostatic management included fresh frozen plasma, platelet transfusion,
      activated prothrombin complex concentrates, and recombinant factor VIIa. Only 2
      patients received immunomodulatory treatment. FV-i mixing studies with normal
      pooled plasma (n = 26) demonstrated inhibition on immediate mix but progressive
      inhibition after 1 h of incubation could not be demonstrated. 71% of platelet
      neutralization procedures were falsely positive while 59% of DRVVT assays were
      indeterminate. CONCLUSION: FV-i demonstrates immediate inhibition on mixing
      studies; however our limited data does not support a time dependent inhibition.
      Our clinical cohort confirms the variable clinical phenotype for individuals with
      FV-i and supports the notion that management of FV-i should be guided by clinical
      symptoms and not FV:C or FV-i titer.

PMID- 30227316
TI  - Polar bear health in environmental science and translational medicine.

PMID- 30227317
TI  - Individual variation in temporal relationships between exposure to radiofrequency
      electromagnetic fields and non-specific physical symptoms: A new approach in
      studying 'electrosensitivity'.
AB  - BACKGROUND: Everyday exposure to radiofrequency electromagnetic fields (RF-EMF)
      emitted from wireless devices such as mobile phones and base stations, radio and
      television transmitters is ubiquitous. Some people attribute non-specific
      physical symptoms (NSPS) such as headache and fatigue to exposure to RF-EMF. Most
      previous laboratory studies or studies that analyzed populations at a group level
      did not find evidence of an association between RF-EMF exposure and NSPS.
      OBJECTIVES: We explored the association between exposure to RF-EMF in daily life
      and the occurrence of NSPS in individual self-declared electrohypersensitive
      persons using body worn exposimeters and electronic diaries. METHODS: We selected
      seven individuals who attributed their NSPS to RF-EMF exposure. The level of and
      variability in personal RF-EMF exposure and NSPS were determined during a three
      week period. Data were analyzed using time series analysis in which exposure as
      measured and recorded in the diary was correlated with NSPS. RESULTS: We found
      statistically significant correlations between perceived and actual exposure to
      wireless internet (WiFi - rate of change and number of peaks above threshold) and
      base stations for mobile telecommunications (GSM + UMTS downlink, rate of change)
      and NSPS scores in four of the seven participants. In two persons a higher EMF
      exposure was associated with higher symptom scores, and in two other persons it
      was associated with lower scores. Remarkably, we found no significant
      correlations between NSPS and time-weighted average power density, the most
      commonly used exposure metric. CONCLUSIONS: RF-EMF exposure was associated either
      positively or negatively with NSPS in some but not all of the selected self
      declared electrohypersensitive persons.

PMID- 30227318
TI  - Canadian chronic myeloid leukemia outcomes post-transplant in the tyrosine kinase
      inhibitor era.
AB  - The majority of patients with TKI failure respond to HCT. However, the relapse
      risk remains high. This study has evaluated transplant outcomes in 223 CML
      patients with TKI failure due to resistance (n = 132) or intolerance (n = 29), as
      well as those that were TKI naive/responding with advanced disease (n = 35) or
      with chronic phase (CP, n = 27). We studied outcomes according to post-transplant
      BCR-ABL transcript level within 3 months. With respect to transplant outcomes
      according to the post-transplant BCR/ABLtranscript level within 3 months, the
      group failing to achieve a 1.3 log reduction (n = 14, 12.4%) showed the highest
      relapse rate of 78.6% at 5 years, compared to 26.2% and 24.1% in the groups
      achieving 1.3-4.0 log reduction (n = 45, 39.8%), and >=4.1 log reduction (n = 54,
      47.8%) respectively (p < 0.001). Multivariate analysis confirmed that the group
      failing to achieve a 1.3 log reduction had a 2.3-fold higher risk of death and
      6.6 times higher risk of relapse. Poor overall survival after HCT was associated
      with advanced disease at diagnosis, but not disease status prior to HCT. Of 61
      patients who relapsed after HCT, 47 were treated with post-transplant TKI
      therapy; those receiving TKI after loss of MR2 or MMR showed higher rates of
      response and survival compared to those receiving TKI after hematologic relapse
      (p < 0.001). QPCR log reduction level within 3 months post transplantation is
      prognostic in this population.

PMID- 30227319
TI  - Preoxygenation during induction of anesthesia in non-critically ill patients: A
      systematic review.
AB  - We conducted a systematic review of the literature to better understand whether
      preoxygenation in non-critically ill patients (i.e. elective surgery patients)
      should be recommended, as it lengthens safe apnea time (the time required to
      reach oxygen saturation < 90% in an apneic patient). Furthermore, we looked for
      the most efficient technique amongst those currently employed in clinical
      practice. We searched Scopus, CINAHL, the Cochrane Library, PubMed and MeSH using
      various combinations of the words "preoxygenation", "general anesthesia",
      "induction", "operating room" and "oxygen". RCTs conducted on adult (>18 years)
      and non-emergent patients between 2008 and 2017 were deemed eligible. A total of
      11 papers were included. Our review suggests that preoxygenation is a safe and
      efficient technique that allows for longer safe apneic periods in obese (BMI >
      30) non-critically ill patients. Non-obese (<30 BMI) patients do not seem to
      benefit as much from this procedure. However, there is insufficient evidence in
      the literature to provide a clear recommendation. For all patients, the procedure
      was safe and well tolerated with no harm reported. The best technique for
      preoxygenation appears to be pressure support ventilation plus positive end
      expiratory pressure. In conclusion, preoxygenation should be employed during the
      induction of general anesthesia in obese patients as it allows for a longer safe
      apnea time and causes no harm. Although data regarding efficacy is limited for
      the non-obese population, the procedure was still harmless and should continue to
      be performed pending more robust RCTs. We believe there is sufficient evidence to
      support a RCT that could offer better evidence for this subset of patients
      undergoing non-emergent procedures.

PMID- 30227320
TI  - The intubating laryngeal tube (iLTS-D) for blind intubation in superobese
      patients.

PMID- 30227321
TI  - Minute ventilation assessment in the PACU is useful to predict postoperative
      respiratory depression following discharge to the floor: A prospective cohort
      study.
AB  - STUDY OBJECTIVE: Reliably identifying patients at risk for postoperative
      respiratory depression (RD) remains an unmet need. We hypothesized that defined
      low minute ventilation events (LMVe) near the end of the post-anesthesia care
      unit (PACU) stay identifies patients at RD risk on the general hospital floor
      (GHF). DESIGN: Prospective observational study. SETTING: Tertiary care, urban
      academic medical center. PACU and GHF during the first postoperative night.
      PATIENTS: One hundred-and-nineteen adult, ASA I - III patients undergoing
      elective surgery under general anesthesia completed the study. INTERVENTIONS:
      Data collection from a non-invasive respiratory volume monitor and the patients'
      medical record perioperatively through the first postoperative night.
      MEASUREMENTS: Minute ventilation (MV), tidal volume (TV) and respiratory rate
      (RR) were measured continuously in the PACU and on the GHF. MV was counted as the
      percent of individual predicted MV (MVPRED), and RD was defined as >=1 LMVe/h on
      the GHF. Based on the number of LMVes within 30 min before PACU discharge,
      patients were grouped into A, 'Not-At-Risk': 0 LMVe and B, 'At-Risk': >=1 LMVes.
      Unpaired t-test, Mann-Whitney U test, ANOVA, Kruskal-Wallis test, Fisher's exact
      test, sensitivity and specificity and ROC curve analyses were applied as
      appropriate. MAIN RESULTS: One hundred-and-six (89%) and 13 (11%) patients met
      Group A and B criteria respectively. The latter had more LMVe/h on the GHF
      (median 0.81 vs 0, p <= 0.001), and their MVPRED was significantly less.
      Following opioid administration, the LMVe likelihood was 43% in Group B and 5.6%
      in Group A. As a predictor for RD on the GHF, the number of LMVe in the last 30
      min of PACU, had positive and negative predictive values of 61.5% and 90.6%,
      respectively. CONCLUSION: Minute ventilation assessment in the PACU as described
      in this study can be useful to identify patients at risk for postoperative
      respiratory depression.

PMID- 30227322
TI  - Bergapten inhibits liver carcinogenesis by modulating LXR/PI3K/Akt and IDOL/LDLR
      pathways.
AB  - Oxysterol receptors LXRs (alpha and beta) are recently reported to be one of the
      novel and potential therapeutic targets in reducing cell proliferation and tumor
      growth in different system model. Activation of LXRs is correlated with
      modification of PI3K/Akt pathway. LXRs are also found to play a critical role in
      maintaining lipid homeostatais by regulating ABCA1, IDOL, SREBP1, LDLR and also
      certain lipogenic genes such as FASN and SCD1. In the present study a potential
      furanocoumarin, Bergapten (BeG) has been evaluated for its anticancer property on
      Hepatocellular Carcinoma (HCC) on LXR axis. The molecular docking analysis was
      carried out for BeG on LXR (alpha & beta) using Maestro tool and compared with
      reference ligands. This was followed by in vitro (HepG2 cell lines) and in vivo
      (on NDEA induced HCC in Wistar albino rats) anticancer evaluation of BeG. The
      docking results revealed polar and hydrophobic interactions of BeG with LXR
      (alpha,beta). The in vitro studies revealed the potential of BeG in lowering the
      accumulation of lipid droplets in HepG2 cells which was correlated with increase
      in LXR (alpha,beta) protein expressions. Furthermore, the in vivo studies
      demonstrated the potential of BeG in ameliorating the cancer induced alterations
      in body weight, liver weight and significant restoration of the changes in mRNA
      and protein expressions of LXR(alpha,beta), ABCA1, IDOL, SREBP1 and LDLR. BeG
      also modulated the expressions of PI3K, Akt and certain lipogenic genes like FASN
      and SCD1 and reduced the lipid droplets level in liver cancer cells. These
      results provide evidence and validates the critical role of BeG in maintaining
      the lipid homeostasis and justifies its anticancer potential against NDEA-induced
      HCC.

PMID- 30227323
TI  - Therapeutic effects of Smilax glabra and Bolbostemma paniculatum on rheumatoid
      arthritis using a rat paw edema model.
AB  - Smilax glabra Roxb. (Tufuling) and Bolbostemma paniculatum (Maxim.) Franquet
      (Tubeimu) are used as couplet medicine in traditional Chinese medicine for the
      treatment of arthritis. This study is conducted to provide evidence on their
      therapeutic effects on rheumatoid arthritis (RA) and to explore its possible
      mechanisms of action. The identification and quantification of representative
      components (Astilbin and Tubeimoside I) in the n-butyl alcohol fraction of this
      couplet medicine (BFCM) were carried out by HPLC-UV assays. The contents of
      Astilbin and Tubeimoside I in BFCM were 13.13% (15.434 min) and 3.4% (18.619 min)
      respectively. For the assessment of anti-RA and anti-inflammatory activities, a
      carrageenan-induced paw edema model in rats was used. The swelling rates of paws
      and levels of IL-1beta, IL-6 and TNF-alpha in the swelling tissue were
      determined. We observed that the BFCM exhibited significant inhibitory activity
      on carrageenan-induced paw edema model (p<0.01). The down regulated levels of IL
      1beta, IL-6 and TNF-alpha (all p<0.05) were reported. The results indicate that
      BFCM possesses significant anti-RA and anti-inflammatory effects, and it has a
      potential to be developed as a new therapeutic agent against RA.

PMID- 30227324
TI  - LINC00657 played oncogenic roles in esophageal squamous cell carcinoma by
      targeting miR-615-3p and JunB.
AB  - BACKGROUND: The prognosis of esophageal squamous cell carcinoma (ESCC) is
      relatively poor due to the absence of efficient treatment. In this manuscript, we
      have investigated the specific roles and molecular mechanisms of LINC00657 to
      order to identify novel therapeutic targets for ESCC. METHOD: The LINC00657
      expression in ESCC tissues and cell lines were evaluated by quantitative real
      time PCR. The expression of LINC00657 in ESCC cells was regulated by lentivirus
      transfection. Online bioinformatics analysis tools were used to predict the
      potential targets of LINC00657 and miR-615-3p. TCGA database was used to analyze
      the prognosis of ESCC patients. Transwell, wound healing assay and MTT were
      performed to investigate the ESCC cells' biological functions. JunB expression
      was evaluated by Western blot. RESULT: LINC00657 was moderately increased in ESCC
      both in vivo and in vitro and up regulated by irradiation. LINC00657 knockdown
      could inhibit the migration and proliferation of ESCC cells. And downregulation
      of LINC00657 significantly enhanced the radio-sensitivity. Moreover, LINC00657
      could act as a ceRNA to increase the expression of JunB by binding to miR-615-3p.
      Meanwhile, overexpression of miR-615-3p resulted in anti-tumor effects and led to
      the down-regulation of JunB. Survival analysis from TCGA indicated that ESCC
      patients with higher JunB expression had significant poorer prognosis.
      CONCLUSION: LINC00657 might be involved in regulating ESCC's response to
      radiation; and it functioned as an oncogene in ESCC by targeting miR-615-3p and
      JunB, providing novel potential therapeutic targets.

PMID- 30227325
TI  - 15-HETE protects pulmonary artery smooth muscle cells against apoptosis via SIRT1
      regulation during hypoxia.
AB  - 15-Hydroxyeicosatetraenoic acid (15-HETE) is produced by the catalytic metabolism
      of arachidonic acid by the enzyme 15-lipoxygenase. It is produced during hypoxia,
      and participates in the remodeling of pulmonary artery smooth muscle (PASM).
      Previous research has revealed that sirtuin 1 (SIRT1) involved in apoptosis in
      various cells and tissues. Herein, we attempted to determine whether 15-HETE
      counteracts SIRT1-promoted cell death in murine PASM cells (PASMCs). To verify
      this theory, we investigated changes in SIRT1 concentration in response to the
      counteraction of cell death by 15-HETE. We used western blotting and a terminal
      deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, and
      investigated the survival, nuclear morphology, and mitochondrial potential of the
      cells. Our results revealed that 15-HETE promotes the transcription and
      translation of SIRT1. Moreover, 15-HETE increases viability and impaired
      mitochondrial depolarization, and promotes the expression of Bcl-2 and Bcl-xL in
      PASMCs without serum. The reactions mentioned above were eliminated by SIRT1
      inhibitors (EX 527 and SIRT1 inhibitor IV). Our findings suggest that 15-HETE is
      crucial for the protection of PASMCs against cell death, and the SIRT1 pathway
      may provide a new strategy for pulmonary artery hypertension therapy.

PMID- 30227326
TI  - Silencing of cadherin-17 enhances apoptosis and inhibits autophagy in colorectal
      cancer cells.
AB  - Cadherin-17 (CDH17), a structurally unique member of the non-classical cadherin
      family, is associated with poor survival, cell proliferation, and metastasis in
      colorectal cancer. However, the role of CDH17 in the apoptosis and autophagy of
      colorectal cancer cells remains unclear. Here, we aimed to investigate the effect
      of CDH17 knockdown on autophagy and apoptosis in colorectal cancer cells. We
      inhibited CDH17 expression in KM12SM and KM12C colorectal cancer cells by RNA
      interference and found that silencing of CDH17 significantly inhibited cell
      viability and increased apoptosis in KM12SM and KM12C cells. In addition,
      silencing of CDH17 significantly increased the expression of cleaved caspase-3
      and Bax and decreased the expression of Bcl-2. Concurrently, silencing of CDH17
      significantly inhibited the conversion of LC3-I to LC3-II and decreased the
      formation of LC3+ autophagic vacuoles and the accumulation of acidic vesicular
      organelles, indicating that autophagy was significantly inhibited in KM12SM and
      KM12C cells. Additionally, treatment with the autophagy-specific activator
      rapamycin attenuated apoptosis in CDH17-knockdown cells and as indicated by
      decreased caspase-3 activity, decreased expression of cleaved caspase-3 and Bax,
      and increased expression of Bcl-2. In conclusion, CDH17 silencing induced
      apoptosis and inhibited autophagy in KM12SM and KM12C cells, and this autophagy
      protected the cells from apoptotic cell death.

PMID- 30227327
TI  - LncRNA THOR increases the stemness of gastric cancer cells via enhancing SOX9
      mRNA stability.
AB  - This work aims to explore the roles and mechanisms of long non coding RNA
      (lncRNA) THOR in regulating the stemness of gastric cancer cells. RNA-sequencing
      combined with quantitative real-time PCR (qRT-PCR) indicated that lncRNA THOR
      level was significantly upregulated in gastric cancer tissues compared with that
      in normal adjacent tissues. Knockdown of THOR attenuated the stemnness of gastric
      cancer cells, evident by the decrease of stemness markers expression and capacity
      of cells spheroid formation. Further RNA-sequencing combined with qRT-PCR and
      western blot analysis demonstrated that expression of transcriptional factor SOX9
      was remarkably decreased in gastric cancer cells with THOR stable knockdown.
      Additionally, RNA immunoprecipitation (RIP) combined with luciferase reporter
      assay revealed that THOR directly bound to SOX9 3' untranslated region (3'UTR),
      but not its 5'UTR or coding area. Notably, overexpression of SOX9 rescued THOR
      knockdown-mediated inhibition on the stemness of gastric cancer cells. Thus, our
      results suggest that THOR could potentiate the stemness of gastric cancer cells
      via directly binding to SOX9 3'UTR.

PMID- 30227328
TI  - MiR-545-3p/MT1M axis regulates cell proliferation, invasion and migration in
      hepatocellular carcinoma.
AB  - Studies have shown that metallothionein 1 M (MT1M) is a tumor suppressor gene
      which is frequently down-regulated in human hepatocellular carcinoma (HCC). The
      methylation of MT1M promoter region is one of the important transcriptional
      regulation mechanisms that contribute to the loss of its expression. In our
      study, we found that there are still half of the 55 HCC tumor tissues in our
      cohort do not share the promoter methylation of MT1M. So, we speculated there
      maybe another mechanism participating in the downregulation of MT1M in HCC. Then,
      we provided evidences that miR-545-3p, which served as a tumor promoter, post
      transcriptionally regulate MT1M in HCC through binding to its untranslated region
      (3'UTR). Taking together, we investigated the role of miR-545-3p in the process
      of HCC through regulating MT1M.

PMID- 30227329
TI  - Fibroblast growth factor 21 regulates glucose metabolism in part by reducing
      renal glucose reabsorption.
AB  - Although previous studies have shown the potential of FGF21 to regulate blood
      glucose in animal and humans, the precise mechanisms of the action have not been
      well explored. The kidney plays a crucial role for glucose homeostasis. The
      purpose of this study is to explore the effect of FGF21 on renal glucose
      reabsorption. Administration of type 2 and type 1 diabetic mice with FGF21
      reduced the transport maximum of glucose in the kidney and enhanced urinary
      glucose excretion in a dose-dependent manner. The inhibition of glucose
      reabsorption results showed little change in diabetic mice treated with Insulin.
      In physiological state, both FGF21 and insulin had no effect on glucose
      reabsorption and urinary glucose excretion. Next, we examined the expression of
      SGLT2 in the kidney, which is an important molecule for renal glucose
      reabsorption. SGLT2 was highly expressed in the kidneys of diabetic mice.
      Administration of FGF21 reduced SGLT2 expression in the kidney of diabetic mice.
      In contrast, the expression of SGLT2 had little change in diabetic mice treated
      with Insulin. FGF21 and Insulin did not promote SGLT2 expression in physiological
      state. To explore the mechanism which drives these changes, we detected the
      expression of PPARdelta in mice and HK-2 cells, which plays a major role in
      regulating SGLT2 expression. Treatment with FGF21 promoted PPARdelta expression
      in diabetic mice, whereas Insulin had no effect on PPARdelta expression. At dose
      of 2 mg/kg FGF21 treatment promoted PPARdelta expression in physiological state,
      whereas at dose of 1 mg/kg FGF21 did not. In HK-2 cells, treatment with FGF21
      enhanced PPARdelta expression, whereas Insulin treatment had no effect on
      PPARdelta expression. Importantly, the expression of SGLT2 and PPARdelta showed
      little change in HK-2 cells when beta-klotho was knocked down. In conclusion, we
      discovered for the first time that FGF21 ameliorates hyperglycemia in part via
      reducing renal glucose reabsorption through PPARdelta mediated SGLT2 pathway.

PMID- 30227330
TI  - SIRT3-mediated cardiac remodeling/repair following myocardial infarction.
AB  - The recent investigations have extensively focused on the importance of sirtuins,
      as a highly conserved family of gene products, particularly SIRT3 in various
      biological and pathological processes. SIRT3, the mitochondrial NAD+-dependent
      deacetylase has been demonstrated to target a broad range of proteins involved in
      the oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism
      homeostasis and cellular death. The critical function of SIRT3 in myocardial
      infarction (MI), which is one of the complex phenotype of coronary artery disease
      and a result of interaction between various genetic and environmental factors, as
      well as in cardiac repair and remodeling post-MI have attracted more attention in
      the recent years. Therefore, in this review, we will summarize important
      literature about the involvement of SIRT3 in cardiac remodeling/repair following
      MI and its potential underlying mechanisms.

PMID- 30227331
TI  - Neuroprotective effects of Bergenia ciliata on NMDA induced injury in SH-SY5Y
      cells and attenuation of cognitive deficits in scopolamine induced amnesia in
      rats.
AB  - Bergenia ciliata (Haw) Sternb. possess immunomodulatory, anti-inflammatory,
      antioxidant, anti-urolithiatic, wound healing, anti-malarial, anti-diabetic and
      anti-cancer properties. Moreover, the methanolic extracts of the rhizomes of the
      plant were found to demonstrate beneficial neuroprotective effects in the
      intracerebroventricular streptozotocin-induced model in rats. Thus, the present
      study was undertaken to further explore the neuroprotective potential of the
      aqueous (BA) and methanolic extracts (BM) of B. ciliata through various in-vitro
      and in-vivo studies. Both the extracts at all tested concentrations i.e. 50
      50,000 ng/mL did not cause any significant reduction of cell viability of SH-SY5Y
      cells when tested for 48 h when assessed through MTT and resazurin metabolism-
      based cell viability assays. The pre-treatment with the extracts could confer
      significant (p < 0.001) and dose-dependent protective effects against NMDA
      induced injury in SH-SY5Y cells. BM [IC50: 5.7 and 5.19 MUg/mL for
      acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) respectively] led
      to more potent inhibition of both the enzymes as compared to BA (IC50: 227.12 and
      23.25 MUg/mL for AChE and BuChE respectively). BM also proved to be a 1.85-fold
      better scavenger of the DPPH free radicals as compared to BA. Thus, BM was taken
      further for the evaluation of the beneficial effects of 14-day pre-treatment in
      rats in the scopolamine (2 mg/kg, i.p.) induced amnesia model at 125, 250 and 500
      mg/kg, p.o. BM pre-treatment at 250 and 500 mg/kg could significantly ameliorate
      the cognitive impairment (p < 0.001), inhibit AChE (p < 0.001) and BuChE (p <
      0.05) activity, restore GSH levels (p < 0.05) in serum and brain homogenates and
      recover the morphology of hippocampal neurons back to normal. Moreover, the BM
      administration at 500 mg/kg also showed beneficial effects through the
      significant (p < 0.05) reduction of Abeta1-42, phosphorylated tau (p-tau) and GSK
      3beta immunoreactivity in the brain homogenates of the intracerebroventricularly
      streptozotocin (ICV STZ) injected rats as observed from the results of the ELISA
      assays. The outcomes of the study unveiled that BM exerts its beneficial effects
      through prevention of NMDA induced excitotoxic cell death, dual cholinesterase
      inhibition, antioxidant activity coupled with the reduction of the
      immunoreactivity for the Abeta1-42, p-tau and GSK-3beta indicating its potential
      to be screened further for various other models to determine the exact mechanism
      of action.

PMID- 30227332
TI  - Contextual priming of word meanings is stabilized over sleep.
AB  - Evidence is growing for the involvement of consolidation processes in the
      learning and retention of language, largely based on instances of new linguistic
      components (e.g., new words). Here, we assessed whether consolidation effects
      extend to the semantic processing of highly familiar words. The experiments were
      based on the word-meaning priming paradigm in which a homophone is encountered in
      a context that biases interpretation towards the subordinate meaning. The
      homophone is subsequently used in a word-association test to determine whether
      the priming encounter facilitates the retrieval of the primed meaning. In
      Experiment 1 (N = 74), we tested the resilience of priming over periods of 2 and
      12 h that were spent awake or asleep, and found that sleep periods were
      associated with stronger subsequent priming effects. In Experiment 2 (N = 55) we
      tested whether the sleep benefit could be explained in terms of a lack of
      retroactive interference by testing participants 24 h after priming. Participants
      who had the priming encounter in the evening showed stronger priming effects
      after 24 h than participants primed in the morning, suggesting that sleep makes
      priming resistant to interference during the following day awake. The results
      suggest that consolidation effects can be found even for highly familiar
      linguistic materials. We interpret these findings in terms of a contextual
      binding account in which all language perception provides a learning opportunity,
      with sleep and consolidation contributing to the updating of our expectations,
      ready for the next day.

PMID- 30227333
TI  - Weighing outcome vs. intent across societies: How cultural models of mind shape
      moral reasoning.
AB  - Mental state reasoning has been theorized as a core feature of how we navigate
      our social worlds, and as especially vital to moral reasoning. Judgments of moral
      wrong-doing and punish-worthiness often hinge upon evaluations of the
      perpetrator's mental states. In two studies, we examine how differences in
      cultural conceptions about how one should think about others' minds influence the
      relative importance of intent vs. outcome in moral judgments. We recruit
      participation from three societies, differing in emphasis on mental state
      reasoning: Indigenous iTaukei Fijians from Yasawa Island (Yasawans) who
      normatively avoid mental state inference in favor of focus on relationships and
      consequences of actions; Indo-Fijians who normatively emphasize relationships but
      do not avoid mental state inference; and North Americans who emphasize individual
      autonomy and interpreting others' behaviors as the direct result of mental
      states. In study 1, Yasawan participants placed more emphasis on outcome than
      Indo-Fijians or North Americans by judging accidents more harshly than failed
      attempts. Study 2 tested whether underlying differences in the salience of mental
      states drives study 1 effects by inducing Yasawan and North American participants
      to think about thoughts vs. actions before making moral judgments. When induced
      to think about thoughts, Yasawan participants shifted to judge failed attempts
      more harshly than accidents. Results suggest that culturally-transmitted concepts
      about how to interpret the social world shape patterns of moral judgments,
      possibly via mental state inference.

PMID- 30227334
TI  - Physicochemical evolutions of starch/poly (lactic acid) composite biodegraded in
      real soil.
AB  - Plastic pollution is a major environmental problem and the waste disposal is a
      challenge in this case. Poly (lactic acid) (PLA) based biodegradable materials is
      one of the most attractive polymers which can fulfill the current demand. In this
      work, the degradation of starch/PLA composite was investigated in real soil
      environment. The weight loss results demonstrated that the degradation rate of
      PLA could be accelerated by starch. Scanning electrical microscopy (SEM) and
      Fourier transform infrared (FTIR) results showed that the samples degraded faster
      with the presence of starch. The mechanical strengths had an abrupt decrease for
      the starch/PLA composite while that of PLA only decreased in a low degree. The
      distribution of carboxyl group intensity and carbon atomic percent reflected the
      heterogeneity of biodegradation for starch/PLA composite in soil. Moreover, the
      variation of internal carbon atomic percent was higher than that on the surface,
      demonstrating that the degradation of starch/PLA composite was bulk degradation.
      Based on the role of starch played in starch/PLA composite and the
      physicochemical performance evolutions during biodegradation, it should create a
      scientific basis for people interested in studying the biodegradation of PLA, and
      provide some knowledge about controlling the biodegradation rate of PLA through
      adjusting the content of starch in the composite.

PMID- 30227335
TI  - Nutrient use efficiencies, losses, and abatement strategies for peri-urban dairy
      production systems.
AB  - Manure management is an important aspect of urban livestock production that has a
      profound impact on metropolitan living. Data were collected from 28 dairy farms
      in peri-urban Beijing and analysed to determine farm nitrogen and phosphorus
      flows and costs associated with various manure management options to reduce
      nutrient losses. Dairy production in peri-urban Beijing was characterized by its
      use of high protein diets (16.3-17.0% crude protein), high reliance on imported
      feeds (92-98%), and low manure recycling (3.0-10.8%). Farms of 900-2000 cattle
      showed lower use efficiencies than farms of <900 cattle. Costs of manure handling
      ranged from 0.1 to 1.0 Yuan kg-1 milk. Among various manure treatment options,
      biogas digesters with aerobic lagoons had the lowest N losses and costs,
      justifying their investments. In conclusion, peri-urban dairy production systems
      were contrasting with traditional systems and within their own systems in
      nutrient use efficiency and losses, which was mainly decided by their farm size.
      To improve the nutrient use efficiencies and reduce losses, farmers and managers
      of peri-urban dairy production system should have a full awareness of different
      feed intake and manure management.

PMID- 30227336
TI  - Degradation of sulfadiazine, sulfachloropyridazine and sulfamethazine in aqueous
      media.
AB  - Antibiotics discharged to the environment constitute a main concern for which
      different treatment alternatives are being studied, some of them based on
      antibiotics removal or inactivation using by-products with adsorbent capacity, or
      which can act as catalyst for photo-degradation. But a preliminary step is to
      determine the general characteristics and magnitude of the degradation process
      effectively acting on antibiotics. A specific case is that of sulfonamides (SAs),
      one of the antibiotic groups most widely used in veterinary medicine, and which
      are considered the most mobile antibiotics, causing that they are frequently
      detected in both surface- and ground-waters, facilitating their entry in the food
      chain and causing public health hazards. In this work we investigated abiotic and
      biotic degradation of three sulfonamides (sulfadiazine -SDZ-,
      sulfachloropyridazine -SCP-, and sulfamethazine -SMT-) in aqueous media. The
      results indicated that, in filtered milliQ water and under simulated sunlight,
      the degradation sequence was: SCP > SDZ ~ SMT. Furthermore, the rate of
      degradation clearly increased with the raise of pH: at pH 4.0, half-lives were
      1.2, 70.5 and 84.4 h for SCP, SDZ and SMT, respectively, while at pH 7.2 they
      were 2.3, 9.4 and 13.2 h for SCP, SMT and SDZ. The addition of a culture medium
      hardly caused any change in degradation rates as compared to experiments
      performed in milliQ water at the same pH value (7.2), suggesting that in this
      case sulfonamides degradation rate was not affected by the presence of some
      chemical elements and compounds, such as sodium, chloride and phosphate. However,
      the addition of bacterial suspensions extracted from a soil and from poultry
      manure increased the rate of degradation of these antibiotics. This increase in
      degradation cannot be attributed to biodegradation, since there was no
      degradation in the dark during the time of the experiment (72 h). This indicates
      that photo-degradation constitutes the main removal mechanism for SAs in aqueous
      media, a mechanism that in this case was favored by humic acids supplied with the
      extracts from soil and manure. The overall results could contribute to the
      understanding of the environmental fate of the three sulfonamides studied, aiding
      to program actions that could favor their inactivation, which is especially
      relevant since its dissemination can involve serious environmental and public
      health risks.

PMID- 30227337
TI  - Chitin nanowhisker - Inspired electrospun PVDF membrane for enhanced oil-water
      separation.
AB  - The requirement of promoting a revolution in filtration technology has led to
      growing devotion in advanced functional materials such as electrospun membranes
      for filtering devices as a solution for providing water at lower energy costs. In
      this study, electrospun polyvinylidene fluoride membranes were fabricated by
      reinforcing 0.5 and 1 wt. % of chitin nanowhiskers in order to improve their
      thermal stability, mechanical properties, pure water flux and oil-water
      filtration performance for the possible application as filtration membranes.
      Morphological analysis revealed the porous and fibrous structure of membranes
      which confirmed by BET surface area analysis. Incorporation of chitin
      nanowhiskers improved the mechanical properties of the membranes such as
      elongation at break and tensile strength (specifically at 1 wt. % of chitin
      nanowhisker) while resulted in substantial enhancement of their thermal
      properties. Furthermore, polyvinylidene fluoride/chitin nanowhisker membranes
      showed enhanced oil-water separation ability, while reinforcement of chitin
      nanowhisker led to increase pure water flux rate, which measured as a crucial
      point in filtration membranes. The oil-water separation results compared with a
      commercial polyvinylidene fluoride membrane and the results signified the
      potential of electrospun polyvinylidene fluoride/chitin nanowhisker to be used
      for filtration application.

PMID- 30227338
TI  - Cup-plant potential for biogas production compared to reference maize in relation
      to the balance needs of nutrients and some microelements for their cultivation.
AB  - The study was focused on the assessment of cup-plant (Silphium perfoliatum L.) as
      a potential feedstock for biogas production in comparison to reference maize
      related to the balance needs of nutrients and some microelements for their
      cultivation, especially with use of digestate for fertilization. Field
      experiments were carried out in areas of the Czech Republic with less favorable
      conditions for the cultivation of maize. Obtained results confirmed that cup
      plant can be considered a promising novel crop for biogas production due to high
      yields of biomass (12-18 t/ha DM) and methane (3600-4250 Nm3/ha) competing with
      reference maize grown under the same soil and climatic conditions. The
      biochemical analyses characterizing the feed value of phytomass were conclusively
      better with maize than cup-plant. This corresponds with specific methane yields,
      which is about 5-10% higher in maize (269-319 Nm3/t VS) than in cup-plant (254
      298 Nm3/t VS). On the basis of chemical analyses of tested crops, the uptake of
      basic nutrients (N, P, K, Ca, Mg and S) and selected trace elements
      (microelements B, Fe, Mn, Co, Cu, Mo, Ni and Zn) was determined. Then, using the
      element contents and average yields, it was possible to calculate the annual
      removal of each element from the field with cup-plant and reference maize as the
      basis value for the evaluation of compensatory fertilization needs. With respect
      to the cultivation of tested crops for biogas production, the possibilities of
      their compensatory fertilization were evaluated using digestate from biogas
      plants. The uptake of different nutrients and microelements on tested crops was
      verified. The experiment showed that cup-plant has higher requirements on all
      tested nutrients, except N, and microelements, except Cu and Zn. In the case of
      nutrients, the highest uptake differences between cup-plant and maize were at B
      (about 11* higher), followed by Mg (3.5*) and K (1.8*). In the case of
      microelements, the highest uptake differences were B at (about 9* higher),
      followed by Co (5*), Fe, and Mn (2*). Therefore, increasing yields of cup-plant
      after using these nutrients and microelements for compensative fertilizing can be
      expected. For the mixture of maize and cup-plant (1:1 of VS weight), the higher
      specific methane yield was obtained (292 Nm3/t VS). It was more than expected of
      the average value (286 Nm3/t VS). It cannot be explained by the improvement in
      the feed value of cup-plant and maize mixture, but a possible explanation could
      be the positive synergistic effect of cup-plant due to the better supply with
      biologically active essential nutrients and microelements. In any case, this
      phenomenon deserves more detailed research in the future.

PMID- 30227339
TI  - Evaluating the success of public participation in integrated catchment
      management.
AB  - Recognition of the need to manage the water environment in more holistic ways has
      resulted in the global growth of Integrated Catchment Management (ICM). ICM is
      characterised by horizontal integration, encouraging interdisciplinary working
      between traditionally disparate management sectors, alongside vertical
      integration, characterised by the engagement of communities; central is the
      promotion of participatory governance and management decision-making. ICM has
      been translated into policy through, for example, the EU Water Framework
      Directive and at a national level by policies such as the Catchment Based
      Approach in England. Research exploring the implementation of these policies has
      reported success at a catchment level, but further research is required to
      explore practices of management at local level within catchments. This paper
      presents the findings of participatory research undertaken with a catchment
      partnership in the northeast of England to explore the integration of top-down
      policy translation with how local communities interact with management agencies
      at sub-catchment scale (a bottom-up perspective). The research found that supra
      catchment scale drivers dominate the vertical interplay between management
      systems at more local levels. These drivers embed traditional practices of
      management, which establishes public participation as a barrier to delivery of
      top-down management objectives, resulting in practices that exclude communities
      and participatory movements at the local level. Although collaboration between
      agencies at the partnership scale offers a potential solution to overcoming these
      obstacles, the paper recommends changes to supra-catchment governance structures
      to encourage flexibility in developing local participatory movements as assets.
      Further research is necessary to develop new practices of management to integrate
      local people more effectively into the management process.

PMID- 30227340
TI  - Physical and ecological effects of rehabilitating the geothermally influenced
      Waikite Wetland, New Zealand.
AB  - Pressure to optimise land use and to maximise the economic viability of land has
      had a detrimental impact on wetlands worldwide. Rehabilitating wetlands has been
      identified by resource managers as increasingly important to enhance
      environmental values and restore ecosystem functions that may have been lost
      through developments effecting wetlands. This paper investigates rehabilitating a
      geothermally influenced wetland that had been drained and used for grazing stock.
      The Waikite Wetland (New Zealand) is a relatively unique wetland because the
      primary water source to the wetland has a significant geothermal water component.
      This results in the area hosting populations of rare flora and fauna that are
      significant to New Zealand. A range of management actions that included diverting
      a geothermal stream back into the wetland, blocking drains, pest control, weed
      control, native plantings, fencing and building a weir to increase water levels
      were used to rehabilitate the wetland. This was done to promote thermotolerant
      vegetation growth, restore wetland water levels and minimise pest plant species
      re-establishing while minimising the effects on geothermal surface features and
      allowing indigenous wetland vegetation to re-establish. Physical, chemical and
      vegetation monitoring show that management actions have increased thermotolerant
      vegetation growth in the wetland while having a small potential impact on
      geothermal discharges into the wetland. Increasing the water level in the wetland
      appears to be helping control plant pest species close to the weir, but has also
      made sensitive vegetation growing close to the waterways more susceptible to
      flooding caused by high-intensity rainfall events.

PMID- 30227341
TI  - High electroencephalographic seizure exposure is associated with unfavorable
      outcomes in neonates with hypoxic-ischemic encephalopathy.
AB  - PURPOSE: Electroencephalographic seizures (ES) are common among neonates with
      hypoxic-ischemic encephalopathy (HIE), and they represent a treatable
      complication that might improve neurodevelopmental outcomes. We aimed to
      establish whether higher ES exposure was predictive of unfavorable outcomes while
      adjusting for other important clinical and electroencephalographic parameters.
      METHODS: We performed a single-center, retrospective study of consecutive
      neonates with HIE managed with therapeutic hypothermia from June 2010 through
      December 2016. Neonates underwent continuous electroencephalographic (cEEG)
      monitoring during and after therapeutic hypothermia. Outcome measures included
      abnormal MRIs after rewarming and abnormal motor and language development.
      RESULTS: Clinical data from the perinatal period were available for 116 neonates.
      Follow-up data were available for 93 of 116 (80%) neonates who survived to
      discharge, with a median follow-up period of 23 months (interquartile range 1236
      months). Multivariate analysis demonstrated that high ES exposure (OR 5.2, 95% CI
      1.3-21.2, p = 0.02) and moderate/severely abnormal EEG background (OR 8.3, 95% CI
      1.6-43.9, p = 0.01) were independent predictors of abnormal motor development.
      High ES exposure was an independent predictor of abnormal language development
      (OR 4.2, 95% CI 1.1-15.9, p = 0.04). High ES exposure (OR 7.0, 95% CI 2.2-22.5, p
      = 0.01) and severe encephalopathy (OR 7.9, 95% CI 1.5-42.7, p = 0.02) were
      independent predictors of abnormal MRIs. CONCLUSIONS: Among neonates with HIE
      managed with therapeutic hypothermia, high ES exposure was the most important
      predictor of abnormal developmental and neuroimaging outcomes, even after
      adjustment for multiple clinical and EEG variables. Adequate identification and
      management of ES with judicious use of anti-seizure medications may optimize
      outcomes.

PMID- 30227342
TI  - Experience of psychogenic nonepileptic seizures in the Canadian league against
      epilepsy: A survey describing current practices by neurologists and
      epileptologists.
AB  - PURPOSE: Psychogenic nonepileptic seizures (PNES) are one of the most common
      differential diagnoses of epilepsy. Our objective is to describe current medical
      care in Canada and identify patterns of practice and service gaps. METHODS: In
      2015, a 36-question survey was sent via email to the 131 members of the Canadian
      League Against Epilepsy. The questions were designed after literature review and
      discussion with the ILAE PNES Task Force. Questions were separated into 5
      sections: 1) the role of the respondent and their exposure to PNES, 2) diagnostic
      methods, 3) management of PNES, 4) etiological factors, and 5) problems accessing
      health care. RESULTS: Sixty-two questionnaires were analyzed (response rate:
      47%). Most respondents were epileptologists (76%). The majority of respondents
      personally diagnosed PNES and communicated the diagnosis to the patient, but only
      55% provided follow-up within their practice and only 50% recommended or arranged
      treatment. Many (35%) were either unfamiliar with the diagnosis of PNES or
      inexperienced in arranging or offering treatment. Most (79%) provided follow-up
      to patients with concomitant epilepsy, but when PNES was the sole diagnosis
      follow-up rates were low. Although 84% of respondents felt that individualized
      psychological therapy was the most effective treatment, 40% of patients were not
      referred to psychotherapy and in most cases availability such therapy was low (30
      60%). CONCLUSIONS: Canadian health professionals' understanding of PNES mostly
      reflects current international expert opinion. Once diagnosis is made however,
      the majority of patients are discharged from neurological services without
      appropriate psychological care.

PMID- 30227343
TI  - Magnetic ordered mesoporous carbon materials for adsorption of minocycline from
      aqueous solution: Preparation, characterization and adsorption mechanism.
AB  - In this paper, the effect of cyanoguanidine (CNGE) for tailoring pore size during
      the soft-templating preparation of mesoporous carbon materials was studied. In
      consideration of cyclic utilization, the surface of the mesoporous carbon
      materials were doped with magnetic Fe3O4 particles. The characterization results
      (including TEM, XRD, BET, TGA and FT-IR) showed that adding CNGE did not destroy
      the ordered porous structure; instead, it changed the pore size from 2.98 nm to
      9.42 nm. Besides, the mesoporous carbon materials exhibited a strong magnetic
      response owing to the dopant of Fe3O4 particles. With the increase in CNGE, some
      functional groups were added to the surface of the mesoporous carbon materials,
      which partly promoted the adsorption effect. The results indicated that
      adsorption approached equilibrium in the first 10 min and reached the maximum
      when the pore size was 5.89 nm. The kinetic of minocycline adsorption on magnetic
      ordered mesoporous carbon material could be interpreted by a pseudo-first-order
      model. The adsorption isotherms showed that the adsorption process was complex,
      combining physical and weak chemical adsorption, in good agreement with the Sips
      model.

PMID- 30227344
TI  - Study of the bioavailability of heavy metals from atmospheric deposition on the
      soil-pakchoi (Brassica chinensis L.) system.
AB  - The objective of this study was to investigate the bioavailability of heavy
      metals from atmospheric deposition on the soil-pakchoi (Brassica chinensis L.)
      system near a smelter. Soil reciprocal translocation experiment was conducted
      with seven groups of pot culture (filled with soils of gradient levels of heavy
      metals) in three sites of gradient atmospheric heavy metal depositions. Results
      showed that the newly deposited heavy metals (Cu and Cd) were preferential
      retention in topsoil (0-4 cm) and presented as higher bioavailable fractions
      compared to those in original soils. Atmospheric depositions contributed to 20
      85% of shoot Cu and Cd in high deposition site, which were likely resulted not
      only from the direct transfer of contaminants from atmosphere to foliar but also
      from the atmosphere-soil-root transfer. However, the 52-62% of Pb in shoot from
      atmospheric depositions was mainly resulted from foliar direct uptake. The
      increasing atmospheric heavy metal depositions significantly decreased the
      photosynthetic parameters of pakchoi. Additionally, the potential health risks
      associated with the consumption of pakchoi were elevated in high deposition site
      and the bioaccessibility values were observed up to 56-81%. This study will
      provide useful reference information for the newly deposited heavy metal dynamics
      in the surface environment.

PMID- 30227345
TI  - Time attitudes profile stability and transitions: An exploratory study of
      adolescent health behaviours among high school students.
AB  - PURPOSE: Time attitudes refer to individuals' feelings about the past, present,
      and future, and an increasing number of cross-sectional studies have demonstrated
      that positive time attitudes are significantly related to better health and well
      being. We investigated time attitude profile membership and associated
      transitions longitudinally in United Kingdom-based adolescents, and assessed the
      relationship between time attitude profile development on health behaviours at +
      21 months after the data collection involving time attitudes. METHODS:
      Participants were high school students (N = 1306; 41.8% female, Mage 12.5-14.5
      years [waves 1-3]). The Adolescent and Adult Time Inventory - Time Attitudes
      Scale was employed to identify profiles, and a mover-stayer latent transition
      analysis was employed to examine developmental changes. Data were also gathered
      on sensation seeking, and a range of health indicators were assessed: Past week
      frequency of physical exercise, self-rated health, subjective life expectancy,
      lifetime cannabis and smoking, and dental attendance. RESULTS: Staying in a
      positive time attitude profile was related to higher subjective life expectancy,
      and less frequent use of cannabis and cigarettes (1.00 <= d <= 4.00). Further,
      moving to a positive profile predicted healthier outcomes for most health
      measures used. CONCLUSIONS: Notwithstanding the limitation that health outcomes
      in the present study were distal, the present study bolstered a developing cross
      sectional literature supporting the association between positive time attitudes
      and better health and well-being outcomes. Future longitudinal studies which
      assess measures concurrently are required.

PMID- 30227346
TI  - Ligand free surface of CdS nanoparticles enhances the energy transfer efficiency
      on interacting with Eosin Y dye - Helping in the sensing of very low level of
      chlorpyrifos in water.
AB  - With an aim to sense the presence of chlorpyrifos (CP) pesticide in water,
      fluorescence resonance energy transfer (FRET) between the chemically synthesized
      ligand free CdS nanocrystals (donor) and Eosin Y dye (acceptor) has been studied
      in presence and absence of CP in the FRET pair system. This prepared water
      soluble CdS nanocrystals have been characterized by Transmission Electron
      microscopy (TEM), which shows that CdS nanocrystals are spherical in shape with
      an average size of 5 nm approximately. Further, Fourier Transform Infrared
      Spectroscopic (FTIR) study confirms that these CdS nanocrystals are ligand free
      stable nanocrystals. It has been observed that this CdS nanocrystals and Eosin Y
      FRET pair can strongly sense the presence of chlorpyrifos (CP) pesticide in water
      up to a very low concentration of 10 ppb, which is the sensitivity of detection
      or detection limit. This FRET pair is found to be very simple and cost effective
      for the sensing of toxic pesticide CP.

PMID- 30227347
TI  - An azine-based carbothioamide chemosensor for selective and sensitive turn-on-off
      sequential detection of Zn(II) and H2PO4-, live cell imaging and INHIBIT logic
      gate.
AB  - Hydrazino-carbothioamide, 1, serves as a turn-on fluorescent chemosensor to Zn2+
      and the mixture shows green emission (lambdaem 492) in presence of large number
      of ions with impressive limit of detection (LOD), 0.59 nM. Intense fluorescence
      of Zn-complex is selectively turn-off upon adding H2PO4- only to the limit of
      detection, 26 MUM, while other anions remain silent. The sensing mechanism of 1
      is established by suppressing the ESIPT of 1 and complexation with Zn2+ (CHEF) is
      supported by Job's plot, 1H NMR, and HR-MS data. Turn-on-off sequential detection
      of Zn2+ and H2PO4- also have successfully been employed for the engineering of
      INHIBIT molecular logic gate. The sensor is non-toxic and has been used in
      identifying Zn2+ in the intracellular region of African green monkey kidney cells
      (Vero cells).

PMID- 30227349
TI  - Sudomotor dysfunction is frequent and correlates with disability in Friedreich
      ataxia.
AB  - OBJECTIVES: To evaluate autonomic symptoms and function in Friedreich's Ataxia
      (FRDA). METHODS: Twenty-eight FRDA patients and 24 controls underwent
      clinical/electrophysiological testing. We employed the Friedreich's Ataxia Rating
      Scale (FARS) and the Scales for Outcomes in Parkinson's Disease: Autonomic
      Questionnaire-SCOPA-AUT to estimate the intensity of ataxia and autonomic
      complaints, respectively. Cardiovagal tests and the quantitative sudomotor axonal
      reflex, Q-SART, were then assessed in both groups. RESULTS: In the patient group,
      there were 11 men with mean age of 31.5 +/- 11.1 years. Mean SCOPA-AUT score was
      15.1 +/- 8.1. Minimum RR interval at rest was shorter in the FRDA group (Median
      831.3 * 724.0 ms, p < 0.001). The 30:15 ratio, Valsalva index, E:I ratio, low and
      high frequency power presented no differences between patients and controls (p >
      0.05). Sweat responses were significantly reduced in patients for all sites
      tested (forearm 0.389 * 1.309 uL; proximal leg 0.406 * 1.107 uL; distal leg 0.491
      * 1.232 uL; foot 0.265 * 0.708 uL; p value < 0.05). Sweat volumes correlated with
      FARS scores. CONCLUSIONS: We found abnormal sudomotor but normal heart rate
      variability in FRDA. Small cholinergic post-ganglionic fibers are affected in the
      disease. SIGNIFICANCE: Quantification of sudomotor function might be a biomarker
      for FRDA.

PMID- 30227348
TI  - Bilateral independent periodic discharges are associated with electrographic
      seizures and poor outcome: A case-control study.
AB  - OBJECTIVE: To determine the clinical correlates bilateral independent periodic
      discharges (BIPDs) and their association with electrographic seizures and
      outcome. METHODS: Retrospective case-control study of patients with BIPDs
      compared to patients without periodic discharges ("No PDs") and patients with
      lateralized periodic discharges ("LPDs"), matched for age, etiology and level of
      alertness. RESULTS: We included 85 cases and 85 controls in each group. The most
      frequent etiologies of BIPDs were stroke, CNS infections, and anoxic brain
      injury. Acute bilateral cerebral injury was more common in the BIPDs group than
      in the No PDs and LPDs groups (70% vs. 37% vs. 35%). Electrographic seizures were
      more common with BIPDs than in the absence of PDs (45% vs. 8%), but not than with
      LPDs (52%). Mortality was higher in the BIPDs group (36%) than in the No PDs
      group (18%), with fewer patients with BIPDs achieving good outcome (moderate
      disability or better; 18% vs. 36%), but not than in the LPDs group (24%
      mortality, 26% good outcome). In multivariate analyses, BIPDs remained associated
      with mortality (OR: 3.0 [1.4-6.4]) and poor outcome (OR: 2.9 [1.4-6.2]).
      CONCLUSION: BIPDs are caused by bilateral acute brain injury and are associated
      with a high risk of electrographic seizures and of poor outcome. SIGNIFICANCE:
      BIPDs are uncommon but their identification in critically ill patients has
      potential important implications, both in terms of clinical management and
      prognostication.

PMID- 30227350
TI  - Trends in documented co-occurring conditions in children with autism spectrum
      disorder, 2002-2010.
AB  - BACKGROUND: Autism spectrumdisorder (ASD) commonly presents with co-occurring
      medical conditions (CoCs). Little is known about patterns in CoCs in a time of
      rising ASD prevalence. AIMS: To describe trends in number and type of documented
      CoCs in 8-year-old children with ASD. METHODS: We used Autism and Developmental
      Disabilities Monitoring Network (ADDM) data, a multi-source active surveillance
      system monitoring ASD prevalence among 8-year-old children across the US. Data
      from surveillance years 2002, 2006, 2008, and 2010 were used to describe trends
      in count, categories, and individual CoCs. RESULTS: Mean number of CoCs increased
      from 0.94 CoCs in 2002 to 1.06 CoCs in 2010 (p < 0.001). The percentage of
      children with ASD with any CoC increased from 44.5% to 56.4% (p < 0.001). CoCs
      with the greatest increases were in general developmental disability (10.4% to
      14.5%), language disorder (18.9% to 23.6%), and motor developmental disability
      (10.5% to 15.6%). Sex modified the relationship between developmental (P = 0.02)
      and psychiatric (P < 0.001) CoCs and surveillance year. Race/ethnicity modified
      the relationship between neurological conditions (P = 0.04) and surveillance
      year. CONCLUSIONS: The increase in the percentage of children with ASD and CoCs
      may suggest the ASD phenotype has changed over time or clinicians are more likely
      to diagnose CoCs.

PMID- 30227351
TI  - Early nurture epigenetically tunes the oxytocin receptor.
AB  - Mammalian sociality is regulated in part by the neuropeptide oxytocin. In prairie
      voles, subtle variation in early life experience changes oxytocin receptor
      mediated social behaviors. We report that low levels of early care in voles leads
      to de novo DNA methylation at specific regulatory sites in the oxytocin receptor
      gene (Oxtr), impacting gene expression and protein distribution in the nucleus
      accumbens. DNA methylation state of the blood predicts expression in the brain
      indicating the utility of the blood as a biomarker for the transcription state of
      the brain. These experience-sensitive CpG sites are conserved in humans, are
      related to gene expression in the brain, and have been associated with
      psychiatric disorders and individual differences in neural response to social
      stimuli. These results identify a mechanism by which early care regulates later
      displays of typical prairie vole social behavior and suggest the potential for
      nurture driven epigenetic tuning of OXTR in humans.

PMID- 30227352
TI  - Validation of a new continuous geographic isolation scale: A tool for rural
      health disparities research.
AB  - The purpose of this study was to develop and test a new continuous measure for
      rural health disparities research that characterizes geographic areas according
      to a perspective of access to resources. We call the measure Isolation and
      anticipate it will be useful as an alternative to commonly used rural
      classification schemes (e.g., the Census Bureau's measure). Following the best
      known standards for measuring rurality, it captures the trade-off between access
      to resource-rich, high-population-density areas and the cost of travel to those
      areas; thus even intrinsically low-resource areas may have high access to nearby
      resources. Validity was tested with proxies such as distance to hospitals,
      physician availability, and access to high quality food. The Isolation scale
      demonstrated good construct validity (i.e., both convergent and criterion
      validity). Fit statistics indicated that, compared to other commonly-used
      urban/rural definitions, the Isolation scale was the best overall measure when
      predicting several proxies for rurality, even when categorized. We also show that
      the measure does a substantially better job at explaining national health outcome
      data at the state level. This new continuous Isolation scale shows considerable
      promise for improving our conceptualization, theorization, and measurement of the
      features of rurality that are pertinent to rural health disparities research, and
      can also be useful to policy makers who may find value in using isolation
      thresholds that are most relevant to their policy planning needs.

PMID- 30227353
TI  - Rationally designed divalent caffeic amides inhibit amyloid-beta fibrillization,
      induce fibril dissociation, and ameliorate cytotoxicity.
AB  - One of the pathologic hallmarks in Alzheimer's disease (AD) is extracellular
      senile plaques composed of amyloid-beta (Abeta) fibrils. Blocking Abeta self
      assembly or disassembling Abeta aggregates by small molecules would be potential
      therapeutic strategies to treat AD. In this study, we synthesized a series of
      rationally designed divalent compounds and examined their effects on Abeta
      fibrillization. A divalent amide (2) derived from two molecules of caffeic acid
      with a propylenediamine linker of ~5.0 A in length, which is close to the
      distance of adjacent beta sheets in Abeta fibrils, showed good potency to inhibit
      Abeta(1-42) fibrillization. Furthermore, compound 2 effectively dissociated the
      Abeta(1-42) preformed fibrils. The cytotoxicity induced by Abeta(1-42) aggregates
      in human neuroblastoma was reduced in the presence of 2, and feeding 2 to Abeta
      transgenic C. elegans rescued the paralysis phenotype. In addition, the binding
      and stoichiometry of 2 to Abeta(1-40) were demonstrated by using electrospray
      ionization-traveling wave ion mobility-mass spectrometry, while molecular dynamic
      simulation was conducted to gain structural insights into the Abeta(1-40)-2
      complex.

PMID- 30227354
TI  - Early developing syntactic knowledge influences sequential statistical learning
      in infancy.
AB  - Adults' linguistic background influences their sequential statistical learning of
      an artificial language characterized by conflicting forward-going and backward
      going transitional probabilities. English-speaking adults favor backward-going
      transitional probabilities, consistent with the head-initial structure of
      English. Korean-speaking adults favor forward-going transitional probabilities,
      consistent with the head-final structure of Korean. These experiments assess when
      infants develop this directional bias. In the experiments, 7-month-old infants
      showed no bias for forward-going or backward-going regularities. By 13 months,
      however, English-learning infants favored backward-going transitional
      probabilities over forward-going transitional probabilities, consistent with
      English-speaking adults. This indicates that statistical learning rapidly adapts
      to the predominant syntactic structure of the native language. Such adaptation
      may facilitate subsequent learning by highlighting statistical structures that
      are likely to be informative in the native linguistic environment.

PMID- 30227355
TI  - Process analytical technology for continuous manufacturing tableting processing:
      A case study.
AB  - The use of Near Infrared Spectroscopy (NIRS) as a fast and non-destructive
      technique was employed for the control and monitoring of the tableting step
      during a continuous manufacturing process. Two NIRS methods were optimized in
      order to in-line control the blend uniformity in the tablet feed frame and the
      API concentration of freshly pressed tablets prior the ejection. The novelty of
      this work first lies in the acquisition speed of NIR spectra reaching up to
      70,000 tablets/h. Partial Least Square (PLS) regression was used as chemometric
      tool for the computation that resulted in excellent predictive calibration
      results. A coefficient of correlation (r) value of 0.99 was obtained for both
      probes. The root mean square error of calibration (RMSEC) and the root mean
      square error of prediction (RMSEP) were respectively 1.8% and 1.8% for active
      content in the tablet feeder and 2.2% and 2.3% for the tablet content. In
      addition, calibration performance and robustness of the methods were evaluated.
      Moreover several qualitative methods were proposed to monitor the tableting
      process in different stages of development (single wavelength, Principal
      Component Analysis, and Independent Component Analysis). In early phase
      development, the requirement/quality of the input material is not established
      yet; hence the use of a qualitative approach allows to confirm the suitability of
      the PAT methodology for in-process material monitoring & control. Later, the
      qualitative approach constitutes the foundation for the quantitative approach
      when input materials are fixed and larger production size occurs. The proposed
      strategy is a performant PAT tool for continuous manufacturing and a step forward
      to real time release.

PMID- 30227357
TI  - An ICP-MS platform for metal content assessment of cell culture media and
      evaluation of spikes in metal concentration on the quality of an IgG3:kappa
      monoclonal antibody during production.
AB  - Metal ions can be enzyme cofactors and can directly influence the kinetics of
      biochemical reactions that also influence the biological production and quality
      attributes of therapeutic proteins, such as glycan formation and distribution.
      However, the concentrations of metals in commercially available chemically
      defined media can range from 1 to 25,000 ppb. Because such concentration changes
      can impact cell growth, manufacturing yield and product quality the
      alteration/fluctuation in media composition should be well controlled to maintain
      product quality. Here, we describe a platform of analytical methods to determine
      the composition of several metals in different sample matrices using an advanced
      automated Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). These methods,
      validated to ICH Q2R1 regulatory validation parameters, were successfully applied
      to- (a) screen cell culture media; (b) determine changes in the metal
      concentration during cell growth in spinner flasks, and, (c) determine effect on
      the glycosylation pattern and homogeneity of an IgG3:kappa produced from a murine
      hybridoma cell line in bench-top parallel bioreactors due to a spike in copper
      and iron concentration. Our results show that maintenance of metal content in the
      cell culture media is critical for product consistency of the IgG3:kappa
      produced.

PMID- 30227356
TI  - Urinary and plasma metabolite differences detected by HPLC-ESI-QTOF-MS in
      systemic sclerosis patients.
AB  - Systemic Sclerosis (SSc) is a chronic autoimmune disease whose origin and
      pathogenesis are not yet well known. Recent studies are allowing a better
      definition of the disease. However, few studies have been performed based on
      metabolomics. In this way, this study aims to find altered metabolites in SSc
      patients in order to improve their diagnosis, prognosis and treatment. For that,
      59 SSc patients and 28 healthy volunteers participated in this study. Urine and
      plasma samples were analysed by a fingerprinting metabolomic approach based on
      HPLC-ESI-QTOF-MS. We observed larger differences in urine than plasma
      metabolites. The main deregulated metabolic families in urine were
      acylcarnitines, acylglycines and metabolites derived from amino acids,
      specifically from proline, histidine and glutamine. These results indicate
      perturbations in fatty acid beta oxidation and amino acid pathways in scleroderma
      patients. On the other hand, the main plasma biomarker candidate was 2
      arachidonoylglycerol, which is involved in the endocannabinoid system with
      potential implications in the induction and propagation of systemic sclerosis and
      autoimmunity.

PMID- 30227358
TI  - Masticatory hypofunction effects induced by BTXA injection of hippocampal neurons
      in developing rats.
AB  - BACKGROUND AND OBJECTIVE: In clinical practice, malocclusion is often encountered
      during the period of growth and development of individuals. In addition to
      nutritional imbalance, some studies have found that mastication affects learning
      and memory ability. Tooth loss and masticatory hypofunction have been suggested
      as risk factors of Alzheimer disease. However, relatively little research has
      been done in developing animals. The present study evaluated the relationship
      between masticatory hypofunction and neuropathological changes of the hippocampus
      in developing rats. DESIGN: Four-week-old Wistar rats were randomly divided into
      saline-injected and botulinum toxin type A (BTXA)-injected groups. After an
      experiment period of 4 weeks, the rats were sacrificed for evaluation of
      neuropathological changes in the hippocampus through Nissl staining and
      phosphorylated cyclic AMP (cAMP) response element binding protein (CREB)
      immunohistochemistry. RESULTS: Nissl staining revealed a significant reduction in
      the density of neurons in the BTXA-injected rats. The BTXA-injected rats
      exhibited a decreased level of CREB phosphorylation. The degree of p-CREB
      immunoreactivity differed significantly between the two groups. CONCLUSION: The
      BTXA-injected rats exhibited a reduction in neuron density and phosphorylated
      CREB, indicating that mastication might influence the learning and memory ability
      during the growth period. Therefore, it is strongly suggested that malocclusion
      be corrected as soon as possible during growth and development.

PMID- 30227359
TI  - Ovarian response and follow-up outcomes in women diagnosed with cancer having
      fertility preservation: Comparison of random start and early follicular phase
      stimulation - cohort study.
AB  - OBJECTIVES: To determine response to controlled ovarian stimulation in a random
      start cycle and utilisation of cryopreserved oocytes and embryos in cancer
      patients. STUDY DESIGN: A retrospective cohort study was carried out in an
      assisted reproductive treatment centre. Participants included 137 cancer patients
      who underwent controlled ovarian stimulation for fertility preservation between 1
      Feb 2003 and 30 June 2016. The primary outcome variable was number of oocytes
      retrieved. Multivariable logistic regression analysis was performed, and
      differences compared using Chi squared test and student t-test as appropriate. P
      <  0.05 was considered statistically significant. RESULTS: Using the antagonist
      protocol, there was no difference in number of oocytes retrieved between the
      early follicular phase or at random start stimulation; 11.9 (95% CI 10.3-13.5)
      and 12.9 (95% CI 9.6-16.2), P =  0.602, respectively. Similarly, the number of
      embryos frozen was comparable between those starting stimulation in early
      follicular and random phase, 6.7 (95% CI 5.7-7.7) and 5.1 (95% CI 3.6-6.5), P=
      0.1508 respectively. Among patients undergoing fertility preservation, those who
      returned to attempt a pregnancy had an ongoing pregnancy rate of 24.3%. Overall,
      65% of oocytes and embryos were still in storage, however, 16 (11.7%) had elected
      to have their oocytes or embryos disposed of. CONCLUSION(S): For women faced with
      potential gonadotoxic treatment and requiring urgent fertility preservation,
      ovarian stimulation with the antagonist protocol can be started at random without
      compromising ovarian response. Pregnancy rates following utilisation of frozen
      thawed oocytes and embryos are promising, however, more research is needed to
      understand reasons underlying disposition of oocytes and embryos especially when
      survival following cancer treatment has improved significantly.

PMID- 30227360
TI  - Reducing traffic violations in minority localities: Designing a traffic
      enforcement program through a public participation process.
AB  - The current study tests an innovative public participation process for designing
      and implementing a tailored traffic enforcement program in minority localities.
      The quasi-experiment used two matched pairs of randomly selected Israeli Arab
      localities, where one locality in each pair was randomly assigned to the
      experimental group and the other to the control group. The intervention's main
      features were the public participation process and implementation by police of
      the traffic enforcement program designed during the process. Systematic field
      observations on 12,236 vehicles in the four localities found a meaningful and
      significant reduction in traffic violations in the experimental localities
      following the intervention, while a small increase in violations was observed in
      the control localities. The most meaningful decline, indicating improvement in
      drivers' behavior, was in non-use of seatbelts and small children in the front
      seat. The study suggests that a public participation process which identifies
      local road traffic problems and "dark" hot spots (places where offenses and risky
      behavior recur but might not be known to the police), followed by implementing
      tailored solutions for these problems, can reduce traffic violations. Future
      research should aim to separate out the independent effects of the two phases
      (the public participation process and tailored enforcement).

PMID- 30227361
TI  - Genome packaging of the Bunyavirales.
AB  - The order Bunyavirales comprises nine families of enveloped, negative-strand RNA
      viruses. Depending on the family and genus, bunyaviruses (i.e. now referring to
      all members of the Bunyavirales) contain genomes consisting of two to six
      segments. Each genome segment is encapsidated by multiple copies of the
      nucleocapsid (N) protein and one or a few molecules of the viral polymerase,
      forming so-called ribonucleoproteins (RNPs). Incorporation of RNPs into virions
      is mediated by the interaction of N with the cytoplasmic tails of the structural
      glycoproteins. Although some selectivity exists in the packaging of RNPs into
      virions, which seems to be driven by the 5' and 3'-untranslated regions of the
      genomic RNA segments, evidence is accumulating that bunyavirus genome packaging
      is a stochastic process.

PMID- 30227362
TI  - Antirheumatic Medicine Prescribing Patterns and Direct Medicine Costs in the
      South African Private Health Sector.
AB  - OBJECTIVES: To describe antirheumatic medicine prescribing patterns and to
      estimate the total annual direct medicine cost of rheumatoid arthritis (RA) in
      the private health sector of South Africa. METHODS: A retrospective, cross
      sectional drug utilization study was performed on medicine claims data from
      January 1, 2014, to December 31, 2014, for a total of 4,352 patients with RA.
      Patients were divided into those with RA only and those with RA and other chronic
      disease list conditions. Antirheumatic treatment was categorized into bridge
      therapy (nonsteroidal anti-inflammatory drugs [NSAIDs] and corticosteroids only)
      and therapy for advanced disease (NSAIDs, corticosteroids, and disease-modifying
      antirheumatic drugs [DMARDs] or biologics). Cost-driving products, the 90% drug
      utilization (DU90%) segment, mean, and median medicine item costs were
      calculated. RESULTS: Annual direct RA medicine cost summed to ?4,115,569.70. The
      mean +/- SD (median) cost per medicine item was ?45.87 +/- ?250.35 (?9.01).
      DMARDs represented 47.6% (n = 42,699) and biologics 2.4% (n = 2,150) of the
      89,728 medicine items claimed. The DU90% of bridge therapy products accounted for
      92.8% of the total medicine cost, with celecoxib as the main cost driver because
      of high volume and mean cost. The therapy for advanced disease DU90% segment
      accounted for 34.7% of the total medicine cost, with adalimumab as the main cost
      driver because of high mean cost. CONCLUSIONS: The direct medicine treatment cost
      of RA in the South African private health sector is driven by the high volume of
      DMARDs and the high mean costs of biologics, particularly adalimumab.

PMID- 30227363
TI  - Structural investigation of the enantioselectivity and thermostability mechanisms
      of esterase RhEst1.
AB  - The esterase RhEst1 can catalyze the asymmetric hydrolysis of ethyl (+/-)-2,2
      dimethylcyclopropane carboxylate (DmCpCe), yielding a pharmaceutically relevant
      (S)-carboxylic acid. A triple mutant RhEst1A147I/V148F/G254A showed a 5-fold
      increase in the catalytic activity but a significant decrease in the
      enantioselectivity. Further optimization studies led to a new enzyme with an
      additional A143T mutation, which showed both increased catalytic activity and
      recovered enantioselectivity as well as improved thermostability. To reveal the
      detailed structural mechanisms for these improved properties, we performed all
      atom molecular dynamics simulations on the wild type and two mutants
      A147I/V148F/G254A and A143T/A147I/V148F/G254A RhEst1, in complex with R-DmCpCe
      and S-DmCpCe substrates, respectively. The structural stability of the enzyme
      variants was investigated with the residue interaction network analysis. In
      RhEst1M2, S-DmCpCe was observed to adopt a more "activated" conformation than R
      DmCpCe, with the active site residues better prearranged for the reaction,
      leading to the improved enantioselectivity towards S-DmCpCe. The mutations in the
      two mutants, especially A143T, could lead to different motion patterns in the cap
      domain, thus affecting the structure of the substrate entrance tunnel. The
      residue interaction networks analysis showed an increased number of interactions
      in RhEst1M1 and RhEst1M2 as compared to the wild type enzyme, especially the pi
      pi stacking interactions between Phe148 and the nearby residues, providing an
      explanation for the increased thermostability of the two mutant enzymes observed
      experimentally. Our work provides essential molecular insights into the substrate
      binding, enantioselectivity and structural stability of esterase RhEst1, which
      will facilitate the development of more efficient RhEst1 variants for
      pharmaceutical applications.

PMID- 30227364
TI  - Understanding domain movements and interactions of Pseudomonas aeruginosa lipase
      with lipid molecule tristearoyl glycerol: A molecular dynamics approach.
AB  - Lipases are biocatalysts which exhibit optimal activity at the aqueous-lipid
      interface. Molecular Dynamics (MD) Simulation studies on lipases have revealed
      the structural changes occurring in the enzyme, at the loop-helix-loop, often
      designated as the "lid", which is responsible for its interfacial activation. In
      recent years, MD simulation of lipases at molecular level have been studied in
      detail, whereas very few studies are carried over on its interaction with lipid
      molecules. Hence, in the current study we have investigated molecular interaction
      of bacterial lipase (Pseudomonas aeruginosa lipase, PAL) with a lipid molecule
      (tristearoyl glycerol, TGL). This provides an insight into the interfacial
      activation of the enzyme. The lipid molecule was placed near the lids of the
      enzyme and MD simulations were performed for 100 ns to understand the nature and
      site of the interaction. The results clearly indicate that, the presence of a
      lipid molecule near the lids affects the motion of the enzyme through changes in
      conformation. Lipid molecule near the lids reduces the movements of both lids,
      and the TGL molecule was observed moving towards the active site. The movement of
      the lids, surface accessibility and the domain movements of PAL are discussed and
      the results provide valuable insight in to the role played by the two lids in the
      interfacial activation of PAL with TGL.

PMID- 30227365
TI  - Quantitative structure-activity relationship of the thymidylate synthase
      inhibitors of Mus musculus in the series of quinazolin-4-one and quinazolin-4
      imine derivatives.
AB  - A quantitative structure-activity relationship analysis of the 2-methylquinazolin
      4-one and quinazolin-4-imine derivatives, well-known antifolate thymidylate
      synthase (TYMS) inhibitors, has been performed in the range IC50 = 0.4/380000.0
      nmoL/L using the GUSAR 2013 program. Based on the MNA and QNA descriptors using
      the self-consistent regression, 6 statistically significant consensus models for
      predicting the IC50 numerical values have been constructed. These models
      demonstrate high and moderate prognostic accuracies for the training and external
      validation test sets, respectively. The molecular fragments of TYMS inhibitors
      regulating their antitumor activity are identified. The obtained data open
      opportunities for developing novel promising inhibitors of TYMS.

PMID- 30227366
TI  - Temperature dependence of thermodynamic properties of MoS2 monolayer and single
      wall nanotubes: Application of the developed three-body force field.
AB  - MoS2 nanostructures, especially mono-, multilayer nanothin films as well as
      single- and multiwall nanotubes are rather interesting popular objects in
      nanomaterials chemistry. The thermodynamic properties of inorganic nanotubes, and
      the temperature dependence of their properties can be efficiently investigated by
      first-principles and molecular mechanics methods in the framework of harmonic
      approximation. At the same time, only thin single-wall nanotubes are available
      for the first-principles calculations. The classical mechanics is suitable to
      simulate very large atomic systems and their phonon frequencies, but developing
      sufficiently accurate force field is rather tedious work. Herein, we report the
      force field fitted to the experimental and first-principles data on the structure
      of 2H- and 3RMoS2 polytypes of bulk crystal, structure of monolayer and several
      bilayers, vibrational frequencies of 2HMoS2 bulk and monolayer, relative
      energetic stability of polytypes experimental and first-principles data, elastic
      constants, strain energy of a (12, 12) MoS2 nanotube. The thermodynamic functions
      and their temperature dependence for the armchair and zigzag nanotubes are
      calculated within the formalism of molecular mechanics using elaborated
      interatomic potential. The results of molecular mechanics and first-principles
      method application to the thinnest nanotubes are compared.

PMID- 30227367
TI  - Simulations on methane uptake in tunable pillared porous graphene hybrid
      architectures.
AB  - In this article, 3D pillared carbon nanotube (CNT)-porous graphene (PG) nanomesh
      architectures are computationally investigated as methane storage nanocontainer.
      The purpose of this article is to screen the configurations of 3D pillared CNT-PG
      materials and to select the optimal one for maximizing the methane storage
      capacity. Molecular mechanics (MM) calculations and MD simulations are executed
      to depict the structural characteristics and methane adsorption properties. The
      calculated structural parameters coincide well with the empirical conclusions.
      The methane adsorption simulations are systematic investigated as a function of
      geometry variables such as PG interlayer spacing, distance of CNTs, and the
      number of PG sheets in a wide range of pressure. The average adsorption energy of
      methane in different configurations is concentrated between 2 and 4 kcal mol-1.
      The results revealed that the applications of 3D CNT-PG models can significantly
      enhance methane adsorption performance in comparison to pillared graphene: the
      maximum amount of adsorbed methane of 3D CNT-PG displays 21.3 mmol/gr (interlayer
      spacing of 1.2 nm and bilayer PG), which is about 25% higher than that of
      pillared graphene. Meanwhile, the deformation of (6, 6) carbon nanotubes can
      significantly improve the methane storage capacity. This provides a viable
      structure modification method, which is suitable for enhancement of methane
      storage.

PMID- 30227368
TI  - Concentration dependent adsorption of aromatic organic compounds by SWCNTs:
      Quantum-mechanical descriptors for nano-toxicological studies of biomolecules and
      agrochemicals.
AB  - For evaluating the environmental risk associated using carbon nanotubes (CNTs), a
      successful prediction is desired for the adsorption of organic compounds (OCs) by
      CNTs at different adsorbate concentrations. This is most often achieved through
      poly-parameter linear solvation energy relationships (LSERs) based on
      solvatochromic descriptors. This study examines the real predictivity of the
      existing LSERs for predicting the adsorption of OCs by single-walled CNTs
      (SWCNTs) while comparing it with that of the models developed in the present work
      using quantum-mechanical descriptors. The real predictivity of the quantum
      mechanical models and existing LSERs is compared using state-of-the-art
      statistical procedures employing an external prediction set of compounds not used
      in the model development. The quantum-mechanically computed mean polarizability,
      but originating from the interactions between electrons of parallel spin, is
      found to play an essential role in the adsorption of OCs by SWCNTs. Besides the
      solvatochromic descriptors (McGowan volume and molar excess refractivity), the
      instantaneous inter-electronic interactions, captured through electron
      correlation based quantum-mechanical descriptors, are found to significantly
      affect the adsorption at varying adsorbate concentration. The models developed
      using a combination of quantum-mechanical and solvatochromic descriptors are
      found to be quite reliable. The models proposed were further employed to predict
      the adsorption of agrochemicals such as insecticides, pesticides, herbicides, as
      well as adsorption of endocrine disruptors and biomolecules such as nucleobases
      and steroid hormones. These are predicted to be strongly adsorbed by SWCNTs with
      Progesterone and Guanine exhibiting maximal interaction with the SWCNTs among
      biomolecules. The quantum-mechanical descriptors proposed in this work can be
      used for the risk assessment of SWCNTs in systems where adsorption is the primary
      process.

PMID- 30227369
TI  - The variation of mitochondrial NADH dehydrogenase subunit 4 (mtND4) and molecular
      dynamics simulation of SNPs among Iranian women with breast cancer.
AB  - Breast cancer is the second cause of death among women all around the world. One
      out of every eight women is diagnosed with breast cancer in Iran. There are many
      reasons for cancer, one of which is the mutations in the mitochondrial genome
      observed in most breast cancer studies. However, the aim of this study is to
      evaluate the genetic region of NADH dehydrogenase subunit 4 in patients with
      breast cancer. First, the genomic DNA was extracted from a tissue. The NADH
      dehydrogenase subunit 4 coding region was amplified by PCR, and then the SSCP was
      sequenced. After that, the molecular dynamics were employed. The association
      between the mutations and the prognostic factors such as ER, PR, HER-2, and age
      were statistically examined. The sequence of the ND4 area was determined in 24
      suspected patients, and 15 nucleotide changes were reported. The role of this
      variations was investigated by in-silico. The harmful mutations were predicted
      based on some servers. The molecular dynamics results showed that there is a
      significant relationship between the mutant protein and the changes in the
      structural conformation. Our results showed that the mutation in the ND4 area
      plays an important role in developing breast cancer. So, it can be concluded that
      the mitochondrial NADH dehydrogenase analysis may help to detect breast cancer in
      the early stages.

PMID- 30227370
TI  - Changes in thallium distribution in the scalp hair after an intoxication
      incident.
AB  - In cases of criminal thallium poisoning, forensic investigation is required to
      identify the amount and time of thallium exposure. Usually, blood and urine
      thallium levels are respectively used as biomarkers. Additionally, hair has the
      unique potential to reveal retrospective information. Although several studies
      have attempted to clarify how thallium is distributed in hair after thallium
      poisoning, none have evaluated the time course of changing thallium distribution.
      We investigated changes in the distribution of thallium in hair at different time
      points after exposure in five criminal thallotoxicosis patients. Scalp hair
      samples were collected twice, at 2.6 and 4.2-4.5months after an exposure incident
      by police. Results of our segmented analysis, a considerable amount of thallium
      was detected in almost all hair sample segments. The thallium exposure date
      estimated from both hair sample collections matched the actual exposure date. We
      found that determination of thallium amounts in hair samples divided into
      consecutive segments provides valuable information about exposure period even if
      a considerable time passes after exposure. Moreover, when estimating the amount
      of thallium exposure from a scalp hair sample, it is necessary to pay sufficient
      attention to individual differences in its decrease from hair.

PMID- 30227371
TI  - Identification of trichothecene-type mycotoxins in toxic mushroom Podostroma
      cornu-damae and biological specimens from a fatal case by LC-QTOF/MS.
AB  - In some autopsy cases, there are unknown natural toxins that are suspected to
      cause serious damage to the person. However, without reference materials, it is
      almost impossible to identify the suspicious natural toxins by GC-MS or LC-MS. In
      this case, a man drank mushroom -liquor with a meal at his home. Seven hours
      later, he was transported to the emergency room, and 12hours later, he died. In
      the ingested mushroom-infused-liquor, there were pieces of mushroom that were
      estimated to be Podostroma cornu-damae (Hypocreaceae) based on their
      morphological characteristics. To identify the species, chemical component
      analysis was conducted using LC-QTOF-MS/MS. Monoisotopic mass, fragment ions, and
      isotope distributions were obtained from the LC-QTOF-MS/MS analysis. In addition,
      fragment ions and structure matching were tested for target compound
      confirmation. In this analysis, several toxic trichothecene-type mycotoxins were
      identified including roridin D, roridin E, roridin Q, satratoxin G, satratoxin H,
      satratoxin H 12'-acetate, satratoxin H 13'-acetate, satratoxin H 12',13'
      diacetate, and verrucarol. At autopsy, heart blood, peripheral blood, and the
      stomach contents were collected, and only satratoxin H was detected in these
      samples. This is the first finding of a trichothecene-type mycotoxin in a human
      biological sample from an expected case of P. cornu-damae intoxication. We
      demonstrated that LC-QTOF-MS/MS analysis was an effective method for mushroom
      intoxication cases in the absence of reference materials. Additionally, the
      experience, knowledge, and analytical methods we obtained in this study will be
      great assets for solving other cases of possible natural toxin intoxication.

PMID- 30227372
TI  - Light motor vehicle collisions with heavy vehicles - Psychosocial and health
      related risk factors of drivers being at-fault for collisions.
AB  - BACKGROUND: Fatal head-on collisions between passenger cars and trucks are
      sometimes thought as self-inflicted death of the passenger car drivers. METHODS:
      A total of 378 Finnish drivers of light motor vehicles (LMV) died in collisions
      with heavy vehicles between the years 2002-2011. These male and female drivers,
      who were considered as being at fault, and whose collisions with heavy vehicles
      occurred in the oncoming vehicle's lane, were explored in relation to information
      on their socio-demographics, physical and mental health condition and driving
      related factors. RESULTS: Cause of death of at-fault LMV drivers, as defined in
      medico-legal examination, was most commonly accidental (51%), followed by suicide
      (32%), undetermined intent (17%) and acute illness (0.3%). Ten-year time trend in
      rates of LMV drivers has remained stable (Annual Percentage Change, APC=-0.03;
      p=0.983), the annual proportion varying between 14%-21%. However, a statistically
      significantly increasing time trend was observed in fatal accidents due to
      suicides (APC=5.31, p=0.028). Generally, at-fault LMV drivers were characterized
      as having mental health problems susceptibility to risk (44%), personal
      relationship problems (33%), long-term physical illness (68%) or medication (35%)
      or driving under influence of alcohol (24%). Male LMV drivers, compared to women,
      were more commonly unmarried, farm/wood/industrial workers and drove alone and
      without a planned destination. Female LMV drivers were, more commonly than men,
      widowed, third degree students, skilled workers, had long term mental
      illnesses/disturbances, drove with family member(s) and their fatal accidents
      occurred in winter. CONCLUSION: The findings give support to the recommendation
      that suicidal ideation must be considered when assessing fitness-to-drive.

PMID- 30227373
TI  - Incarcerated Amyand's hernia: A case report.
AB  - INTRODUCTION: Inguinal hernia may contain vermiform appendix in very rare cases.
      This particular condition is known as Amyand's hernia and it has an incidence of
      1%. Diagnosis is very difficult preoperatively, so it is usually an incidental
      finding. PRESENTATION OF CASE: We report a case of a 80 year old man with an
      irreducible mass in right inguinal region. During surgical procedure an Amyand's
      hernia was identified and we performed hernioplasty sec Trabucco and
      appendectomy. DISCUSSION: According to Losanoff and Basson classification, our
      case was type 1 and its management is very controversial. CONCLUSION: Surgical
      treatment depends on surgeon's experience and on clinical evaluation because
      there are many factors that may increase morbidity and mortality.

PMID- 30227374
TI  - Laparoscopic management for gallstone ileus, case report.
AB  - INTRODUCTION: Gallstone ileus is a rare complication of cholelithiasis leading to
      small intestinal obstruction. Elderly females are commonly affected more than
      male. The diagnosis of this condition is challenging and Rigler's triad is
      pathognomonic. Surgery is mandatory with no clear consensus about the best
      surgical approach that should be adopted. CASE PRESENTATION: An elderly female
      patient, with no previous history of biliary diseases, presented with small bowel
      obstruction. Contrast enhanced computed tomography of the abdomen showed the
      classical Rigler's triad. Total laparoscopic enterolithotomy was performed
      successfully. She had smooth postoperative course and she was followed up
      regularly without occurrence of any biliary disease symptoms during the follow up
      period. CONCLUSION: Gallstone ileus should be considered in differential
      diagnosis of small bowel obstruction mainly in old females with no previous
      history of abdominal surgery. Laparoscopic enterolithotomy is safe, feasible and
      effective when performed by experienced surgeons.

PMID- 30227375
TI  - Conversion to thoracotomy during VATS segmentectomy for treatment of symptomatic
      endobronchial hamartoma.
AB  - INTRODUCTION: Most hamartomas are located peripherally in the lung parenchyma and
      are rarely identified as an endobronchial lesion. Clinically patients with an
      endobronchial hamartoma are often symptomatic and may present with various
      symptoms including: fever, wheezing, hemoptysis and obstructive pneumonia. CASE
      PRESENTATION: A 68-year-old man presented with complaints of fever and cough for
      1 month. Chest X-ray revealed a right infrahilar density, which on chest CT was
      found to be a lesion obstructing the superior segmental bronchus of the right
      lower lobe and extending outside of the bronchus. A round rubbery mass
      obstructing the same segmental bronchus was noticed during bronchoscopy and
      endoscopic biopsy yielded a pathological diagnosis of hamartoma. DISCUSSION:
      Bronchoscopy is most helpful in diagnosis and management of endobronchial
      hamartomas but if the lung distal to the obstruction is irreversibly damaged or
      imaging studies suggest that tumor extends outside of the bronchus, pulmonary
      segmentectomy, lobar resection or even pneumonectomy may be indicated.
      CONCLUSION: When a benign tumor of the lung, as endobronchial hamartoma, is
      located in a segmental bronchus and presents extrabronchial spread, we recommend
      to perform a parenchymal-sparing surgical resection. In this case surgical team,
      however, should keep in mind, due to difficult individual dissection of the
      segmental bronchovascular elements, the possibility of conversion from VATS
      (video-assisted thoracic surgery) to open thoracotomy.

PMID- 30227376
TI  - Gastric carcinoid tumor after laparoscopic gastric banding: Case report of a
      patient with weight regain.
AB  - INTRODUCTION: Although carcinoid tumours are a rare gastrointestinal neoplasm
      with an incidence rate of 1-2.5 cases per 100 000 inhabitants, they are the most
      common neuroendocrine tumour of the stomach. PRESENTATION OF CASE: A 70-year-old
      man consulted for epigastric pain and dyspepsia symptoms. His past medical and
      surgical history included obesity (BMI: 53.9 kg/m2), hypertension,
      hyperlipidemia, diabetes mellitus type 2, cardiac failure and a surgical
      treatment with laparoscopic gastric banding. For the analysis and control of the
      gastric banding an upper gastrointestinal endoscopy was performed evidencing many
      small polyps in the gastric antrum, body and fundus. The histopathological
      examination of the resected specimen revealed a well differentiated carcinoid.
      Laparoscopic surgery for the removal of the gastric banding and the subtotal
      gastrectomy leaving a small gastric remnant of approximately 2-cm in size similar
      to the pouch of a bypass was done. Twelve months after surgery the patient
      presented a body mass index of 36.6 kg /m2. DISCUSSION: Gastric carcinoid
      increased incidence among the obese population, although the causing mechanisms
      are not clear, yet it is likely that metabolic and hormonal effects of the
      obesity play a role. The resection may be performed either endoscopically when
      the lesions are small, or surgically according to the tumor type and size.
      CONCLUSION: The resective gastric bypass or gastrectomy with anastomosis by Roux-
      en- Y bypass may be considered as a treatment of choice for patients who after
      bariatric surgery were diagnosed with gastric carcinoid and weight regain.

PMID- 30227377
TI  - Self-assembly of ellipsoidal particles at fluid-fluid interfaces with an
      empirical pair potential.
AB  - Colloidal particles adsorbed at fluid-fluid interfaces interact via mechanisms
      that can be specific to the presence of interfaces, for instance, lateral
      capillary interactions induced by nonspherical particles. Capillary interactions
      are highly relevant for self-assembly and the formation of surface
      microstructures, however, these are very challenging to model due to the
      multibody nature of capillary interactions. This work pursues a direct comparison
      between our computational modelling approach and experimental results on surface
      microstructures formed by ellipsoidal particles. We begin by investigating the
      accuracy of using pairwise interactions to describe the multibody capillary
      interaction by contrasting exact two- and three-particle interaction energies and
      we find that the pairwise approximation appears reasonable for the experimentally
      relevant configurations studied. We then develop an empirical pair potential and
      use it in Monte-Carlo type simulations to efficiently model the structure
      formation process for relevant particle properties such as aspect ratio, contact
      angle and surface coverage, and succeed in reproducing our experimental
      observations where we spread sterically-stabilised ellipsoidal particles onto an
      oil-air interface at high surface coverage. At lower surface coverages, we find
      that the self-assembly process falls into the diffusion-limited colloid
      aggregation universality class.

PMID- 30227378
TI  - Efficacy of polyurethane graft on cyclodextrin to control drug release for tumor
      treatment.
AB  - Hydrophilicity of cyclodextrin is controlled through grafting of polyurethane of
      varying graft density, thereby maintain the hydrophilic-hydrophobic balance, to
      sustain the drug delivery rate for better tumor treatment. Grafting is verified
      through nuclear magnetic resonance (1H NMR) and other spectroscopic techniques
      along with the hydrodynamic volume measurement of grafted species and the degree
      of substitution has been calculated from the integrated peak areas. Thermal and
      mechanical stability of the graft copolymers have improved significantly with
      respect to cyclodextrin and the formation of smaller blobs having larger in
      number has been obtained from small angle neutron scattering, atomic force
      microscopy and optical images. Sustained drug delivery has been achieved using
      graft copolymer as opposed to burst release in pure cyclodextrin and polyurethane
      and the phenomenon is understood from the specific interactions, as observed
      though spectroscopic and thermal measurement, between graft copolymer and drug
      followed by this novel architecture of the graft copolymers. Biocompatibility of
      graft copolymers has been checked using cellular studies through 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell
      adhesion. Importantly, the cell killing efficiency has been demonstrated by
      embedding anti-cancer drug in polymer matrices causing mortality rate of 80%
      using graft copolymer against meagre 20% using pure drug or drug embedded in
      cyclodextrin and the result is realised from the sustained release of drug from
      the graft copolymer vis-a-vis burst release in other systems. Cellular studies
      have been translated into an animal model showing the efficacy of newly developed
      patch, made of drug embedded in copolymer, towards the significant suppression of
      tumors in mice as compared to control. Histopathological images and biochemical
      parameters indicate the normal body organ/blood in copolymer treated mice against
      severely damaged organ especially liver/blood in the mice treated with pure drug
      or drug embedded in cyclodextrin arising from burst release. Thus, graft
      copolymer with unique architecture is found to be an effective drug delivery
      vehicle for melanoma cancer treatment without side effect.

PMID- 30227379
TI  - Integrated device based on cauliflower-like nickel hydroxide particles-coated
      fabrics with inverse wettability for highly efficient oil/hot alkaline water
      separation.
AB  - In this paper, we report for the first time the fabrication of cauliflower-like
      Ni(OH)2 particles-coated fabrics with inverse special wettability via a facile
      hydrothermal method. The coated fabric is superhydrophilic in air and
      superoleophobic underwater, which can be changed into superhydrophobicity after
      being modified by long-chain fatty acid. After the superhydrophilic fabric is
      wetted by water in advance, hot alkaline water can be removed from the light
      oil/water mixture driven by gravity. Also, heavy oil can be removed from the
      heavy oil/hot alkaline water mixture under the action of gravity using
      superhydrophobic fabric. The separation efficiencies of the two fabrics for
      different mixtures of hot alkaline water and light or heavy oil are more than
      95.8%. Furthermore, a two-way separation device was designed via integrating a
      pair of fabrics with opposite wettability. The device can continuously separate
      oil and water at the same time from oil/hot alkaline water mixture via one-step
      route with high separation efficiency without consideration of the density of the
      oil. Moreover, the superhydrophilic fabric is capable of separating various oil
      in-water emulsions. We believe that the as-prepared fabrics and the designed
      device may find wide application in separating oil from alkaline water.

PMID- 30227380
TI  - Magnetic mesoporous nanospheres supported phosphomolybdate-based ionic liquid for
      aerobic oxidative desulfurization of fuel.
AB  - Phosphomolybdate-based ionic liquid [(C8H17)3NCH3]3PMo12O40 was prepared and
      supported on a magnetic mesoporous silica (gamma-Fe2O3@SiO2@mSiO2) to obtain a
      magnetic mesoporous catalyst. The morphology and components of the catalyst were
      characterized by FT-IR, XRD, XPS, SEM, TEM, nitrogen adsorption-desorption
      isotherms, and VSM. With air as oxidant, the catalyst showed perfect
      desulfurization performance in oxidation of dibenzothiophene (DBT). The removal
      of DBT from model oil could reach 100% within 5 h at 120  degrees C. After
      reaction, the catalyst could be separated by a magnet and recycled at least four
      times without obvious decrease in the catalytic performance.

PMID- 30227382
TI  - Actin-dependent endosomal receptor recycling.
AB  - Endosomes constitute major sorting compartments within the cell. There, a myriad
      of transmembrane proteins (cargoes) are delivered to the lysosome for degradation
      or retrieved from this fate and recycled through tubulo-vesicular transport
      carriers to different cellular destinations. Retrieval and recycling are
      orchestrated by multi-protein assemblies that include retromer and retriever,
      sorting nexins, and the Arp2/3 activating WASH complex. Fine-tuned control of
      actin polymerization on endosomes is fundamental for the retrieval and recycling
      of cargoes. Recent advances in the field have highlighted several roles that
      actin plays in this process including the binding to cargoes, stabilization of
      endosomal subdomains, generation of the remodeling forces required for the
      biogenesis of cargo-enriched transport carriers and short-range motility of the
      transport carriers.

PMID- 30227381
TI  - Synthesis and characterization of amidoxime modified chitosan/bentonite composite
      for the adsorptive removal and recovery of uranium from seawater.
AB  - A novel amidoxime functionalized adsorbent, poly(amidoxime)-grafted
      chitosan/bentonite composite [P(AO)-g-CTS/BT] was prepared by in situ
      intercalative polymerization of acrylonitrile (AN) and 3-hexenedinitrile (3-HDN)
      onto chitosan/bentonite composite using ethylene glycol dimethacrylate (EGDMA) as
      cross linking agent and potassium peroxy disulphate (K2S2O8) as free radical
      initiator. The adsorbent was characterized by Fourier transform infrared
      spectroscopy (FTIR), X-ray diffraction (XRD), Scanning electron microscopy (SEM),
      Energy dispersive spectroscopy (EDS), BET surface area analyser and X-ray
      photoelectron spectroscopy (XPS). Nitrile groups from two monomers converted to
      amidoxime groups and therefore, increases the adsorption efficiency of
      uranium(VI) [U(VI)] from seawater. The optimum pH for U(VI) adsorption was found
      to be 8.0. The adsorbent dosage of 2.0 g/L was sufficient for the complete
      removal of U(VI) from seawater. The kinetic data fitted well with pseudo-second
      order kinetic model which assumes the presence of chemisorption. The equilibrium
      attained within 60 min and well agreement of equilibrium data with Langmuir
      adsorption model confirms monolayer coverage of U(VI) onto P(AO)-g-CTS/BT. The
      maximum adsorption capacity was found to be 49.09 mg/g. Spent adsorbent was
      effectively regenerated using 0.1 N HCl. Six cycles of adsorption-desorption
      experiments were conducted to study the practical applicability and repeated use
      of the adsorbent. The feasibility of the adsorbent was also tested using natural
      seawater. The results show that P(AO)-g-CTS/BT is a promising adsorbent for the
      removal of U(VI) from seawater.

PMID- 30227383
TI  - A useful model to compare human and mouse growth hormone gene chromosomal
      structure, expression and regulation, and immune tolerance of human growth
      hormone analogues.
AB  - Human (h) pituitary growth hormone (GH) is both physiologically and clinically
      important. GH reaches its highest circulatory levels in puberty, where it
      contributes to energy homeostasis and somatogenic growth. GH also helps to
      maintain tissues and organs and, thus, health and homeostasis. A reduction in the
      rate of hGH production begins in middle age but if GH insufficiency occurs this
      may result in tissue degenerative and metabolic diseases. As a consequence, hGH
      is prescribed under conditions of GH deficiency and, because of its lipolytic
      activity, stimulation of hGH release has also been used to treat obesity.
      However, studies of normal GH production and particularly synthesis versus
      secretion are not feasible in humans as they require sampling normal pituitaries
      from living subjects. Furthermore, human (or primate) GH structure and, as such,
      regulation and potential function, is distinct from non-primate rodent GH. As a
      result, most information about hGH regulation comes from measurements of secreted
      levels of GH in humans. Thus, partially humanized hGH transgenic mice, generated
      containing fragments of human chromosome 17 that include the intact hGH gene
      locus and many thousands of flanking base pairs as well as the endogenous mouse
      (m) GH gene provide a potentially useful model. Here we review this mouse model
      in terms of its ability to allow comparison of hGH versus mGH gene expression,
      and specifically: (i) GH locus structure as well as regulated and rhythmic
      expression; (ii) their ability to model a clinical assessment of hGH production
      in response to overeating and hyperinsulinemia as well as a possible effect of
      exercise, and (iii) their hGH-related immune tolerance and thus potential for
      testing hGH-related analogue immunogenicity.

PMID- 30227384
TI  - A R2R3-MYB transcription factor gene, FtMYB13, from Tartary buckwheat improves
      salt/drought tolerance in Arabidopsis.
AB  - Abiotic stress causes various negative impacts on plants, such as water loss,
      reactive oxygen species (ROS) accumulation and decreased photosynthesis. R2R3-MYB
      transcription factors (TFs) play crucial roles in the response of plants to
      abiotic stress. However, their functions in Tartary buckwheat, a strongly abiotic
      and resistant coarse cereal, haven't been fully investigated. In this paper, we
      report that a R2R3-MYB from Tartary buckwheat, FtMYB13, is not an activator of
      transcriptional activity but is located in the nucleus. Moreover, compared to the
      wild type (WT), transgenic Arabidopsis overexpressing FtMYB13 had a lower
      sensitivity to ABA and caused improved drought/salt tolerance, which was
      attributed to the higher proline content, greater photosynthetic efficiency,
      higher transcript abundance of some stress-related genes and the smaller amount
      of reactive oxygen species (ROS) and malondialdehyde (MDA) in the transgenic
      lines compared to WT. Consequently, our work indicates that FtMYB13 is involved
      in mediating plant responses to ABA, as well as salt and drought.

PMID- 30227385
TI  - Direct delineation of myocardial infarction without contrast agents using a joint
      motion feature learning architecture.
AB  - Changes in mechanical properties of myocardium caused by a infarction can lead to
      kinematic abnormalities. This phenomenon has inspired us to develop this work for
      delineation of myocardial infarction area directly from non-contrast agents
      cardiac MR imaging sequences. The main contribution of this work is to develop a
      new joint motion feature learning architecture to efficiently establish direct
      correspondences between motion features and tissue properties. This architecture
      consists of three seamless connected function layers: the heart localization
      layers can automatically crop the region of interest (ROI) sequences involving
      the left ventricle from the cardiac MR imaging sequences; the motion feature
      extraction layers, using long short-term memory-recurrent neural networks, a)
      builds patch-based motion features through local intensity changes between fixed
      size patch sequences (cropped from image sequences), and b) uses optical flow
      techniques to build image-based features through global intensity changes between
      adjacent images to describe the motion of each pixel; the fully connected
      discriminative layers can combine two types of motion features together in each
      pixel and then build the correspondences between motion features and tissue
      identities (that is, infarct or not) in each pixel. We validated the performance
      of our framework in 165 cine cardiac MR imaging datasets by comparing to the
      ground truths manually segmented from delayed Gadolinium-enhanced MR cardiac
      images by two radiologists with more than 10 years of experience. Our
      experimental results show that our proposed method has a high and stable accuracy
      (pixel-level: 95.03%) and consistency (Kappa statistic: 0.91; Dice: 89.87%; RMSE:
      0.72  mm; Hausdorff distance: 5.91  mm) compared to manual delineation results.
      Overall, the advantage of our framework is that it can determine the tissue
      identity in each pixel from its motion pattern captured by normal cine cardiac MR
      images, which makes it an attractive tool for the clinical diagnosis of
      infarction.

PMID- 30227386
TI  - Epigenetic crossroads of the Epstein-Barr virus B-cell relationship.
AB  - Epstein-Barr virus (EBV) is a gamma-herpesvirus that establishes lifelong
      infection in the majority of people worldwide. EBV uses epigenetic reprogramming
      to switch between multiple latency states in order to colonize the memory B-cell
      compartment and to then periodically undergo lytic reactivation upon plasma cell
      differentiation. This review focuses on recent advances in the understanding of
      epigenetic mechanisms that EBV uses to control its lifecycle and to subvert the
      growth and survival pathways that underly EBV-driven B-cell differentiation
      versus B-cell growth transformation, a hallmark of the first human tumor virus.
      These include the formation of viral super enhancers that drive expression of key
      host dependency factors, evasion of tumor suppressor responses, prevention of
      plasmablast differentiation, and regulation of the B-cell lytic switch.

PMID- 30227388
TI  - Phosphodiesterase 4 inhibitor activates AMPK-SIRT6 pathway to prevent aging
      related adipose deposition induced by metabolic disorder.
AB  - Rolipram is a selective phosphodiesterase 4 (PDE4) inhibitor that exerts a
      variety of effects, including anti-inflammatory, immunosuppressive, and anti
      tumor effects. The aim of this study was to investigate the effect of rolipram on
      metabolic disorder and its underlying mechanisms. Metabolic disorder was induced
      in 8-week-old wild type BABL/c mice by administration of D-galactose for 4 weeks.
      Simultaneously the mice were administered vehicle or rolipram. Alternatively,
      beginning at 3 or 21 months, the mice were administered db-cAMP for 3 months,
      with or without a high-fat-diet (HFD) to induce metabolic disorder. In both
      models, better metabolic function was observed in rolipram-treated mice. Rolipram
      reduced adipose deposition and inflammation and reserved metabolic disorder.
      Treatment with rolipram increased the AMPK phosphorylation and SIRT6 levels in
      the liver and kidney while reducing NF-kappaB acetylation. In vitro, these
      effects were blocked by suppression of SIRT6 expression using specific siRNA.
      Increased cAMP levels reduced excessive adipose deposition, and improved adipose
      distribution in presenile mice. These findings provide a promising strategy for
      the treatment of aging-related metabolic dysfunctions and suggest that selective
      PDE4 inhibitors may be useful agents for the treatment of aging-related metabolic
      diseases.

PMID- 30227387
TI  - Heat-induced longevity in budding yeast requires respiratory metabolism and
      glutathione recycling.
AB  - Heat-induced hormesis is a well-known conserved phenomenon in aging,
      traditionally attributed to the benefits conferred by increased amounts of heat
      shock (HS) proteins. Here we find that the key event for the HS-induced lifespan
      extension in budding yeast is the switch from glycolysis to respiratory
      metabolism. The resulting increase in reactive oxygen species activates the
      antioxidant response, supported by the redirection of glucose from glycolysis to
      the pentose phosphate pathway, increasing the production of NADPH. This sequence
      of events culminates in replicative lifespan (RLS) extension, implying decreased
      mortality per generation that persists even after the HS has finished. We found
      that switching to respiratory metabolism, and particularly the consequent
      increase in glutathione levels, were essential for the observed RLS extension.
      These results draw the focus away solely from the HS response and demonstrate
      that the antioxidant response has a key role in heat-induced hormesis. Our
      findings underscore the importance of the changes in cellular metabolic activity
      for heat-induced longevity in budding yeast.

PMID- 30227389
TI  - Pediatric Auditory Brainstem Implantation: Impact on Audiological Rehabilitation
      and Tonal Language Development.
AB  - OBJECTIVE: This is a retrospective review of the impact of an Auditory Brainstem
      Implant (ABI) on the audiological rehabilitation and tonal language development
      of pediatric patients with prelingual profound deafness in Hong Kong. RESULTS:
      From January 2009 to February 2015, 11 pediatric patients with profound
      prelingual deafness received an ABI in Hong Kong (age range 1.67-3.75 years).
      Etiologies included Cochlear Nerve Deficiency in 7, Severe Cochlear Malformations
      in 2, and Retrocochlear Deafness in 2. All of them were rehabilitated in
      Cantonese, a dialect of Chinese. Standard pediatric cochlear implant outcome
      measurements were used in this study that comprised of the 7-Sound Detection,
      Syllable Identification, Vowel Identification, Consonant Identification, Tone
      Imitation, Tone Production and Speech Perception Category. Audiological
      rehabilitation and speech development outcomes were reviewed. Age-matched
      outcomes of pediatric cochlear implant users were used for comparisons.
      CONCLUSION: Encouraging results of speech development were found, especially with
      continued use of the ABI. There was considerable variation in outcomes. Children
      with coexisting developmental and nonauditory cognitive disabilities did not
      perform as well. Auditory brainstem implantation is a safe and beneficial
      treatment for profound prelingual deafness in Cantonese-speaking pediatric
      patients.

PMID- 30227390
TI  - Fat-to-Lean Mass Ratio Can Predict Cardiac Events and All-Cause Mortality in
      Patients Undergoing Hemodialysis.
AB  - BACKGROUND: Although higher body mass index (BMI) is associated with better
      survival in patients undergoing dialysis, BMI is not an adequate obesity
      indicator. We hypothesized that the fat-to-lean (F/L) mass ratio could be a
      suitable marker of nutritional status and evaluated its prognostic impact on long
      term outcomes in patients undergoing hemodialysis (HD). METHODS: In total, 131
      patients undergoing HD were recruited and monitored prospectively for up to 5
      years. Body composition was analyzed, and other nutritional and inflammatory
      parameters were measured. RESULTS: The mean age of the cohort was 60.7 +/- 13.6
      years, and 65 patients were diabetic. Age, sex, diabetes, comorbidity, and
      inflammation were associated significantly with the F/L mass ratio. During the
      follow-up period, 21 patients experienced cardiac events and 22 patients died.
      Patients with higher F/L mass ratios had significantly higher risks of all-cause
      death (hazard ratio [HR] 3.61, 95% CI 1.07-12.13; p = 0.038) and cardiac events
      (HR 3.54, 95% CI 1.05-11.94; p = 0.041) than those with lower F/L mass ratios.
      CONCLUSIONS: The F/L mass ratio was a useful surrogate marker of nutritional and
      inflammatory status, and an independent predictor of cardiac events and all-cause
      mortality, in patients undergoing HD.

PMID- 30227392
TI  - Differences in Clinical Course of Intraprocedural and Delayed Perforation Caused
      by Endoscopic Submucosal Dissection for Colorectal Neoplasms: A Retrospective
      Study.
AB  - BACKGROUND: Although the use of endoscopic submucosal dissection (ESD) as a
      minimally invasive treatment for large superficial colorectal neoplasms is
      increasing, colorectal ESD remains technically challenging. As perforation in the
      colorectum is generally considered to be associated with a higher risk of
      complications, the aim of this study was to investigate the characteristics of
      perforation caused by colorectal ESD. METHODS: This retrospective study included
      635 lesions treated with colorectal ESD, between February 2011 and December 2015,
      in a tertiary cancer center. We evaluated and compared the clinical course and
      short-term outcomes of the intraprocedural perforation group with those of the
      delayed perforation and no perforation groups. RESULTS: Perforation occurred in
      45 (7.1%) of the 635 cases. Thirty-six cases were intraprocedural perforation
      (5.7%), all of which were successfully closed with endoclips during the
      procedure. Nine cases of delayed perforation occurred (1.4%). No emergency
      surgery was performed in the intraprocedural perforation group; however, 5 of 9
      cases underwent emergency surgery in the delayed perforation group (56%, p <
      0.0001). There were statistically significant differences between the
      intraprocedural and delayed perforation groups with regard to the hospitalization
      period, fasting period, abdominal pain scale, peak white blood cell (WBC) count,
      and peak C-reactive protein (CRP), and between the intraprocedural and no
      perforation groups with regard to the location of the lesion, hospitalization
      period, fasting period, abdominal pain scale, peak WBC, peak CRP, and en bloc
      resection rate. CONCLUSIONS: While intraprocedural perforation due to colorectal
      ESD can be managed conservatively, delayed perforation can lead to serious
      adverse events.

PMID- 30227393
TI  - A New Trans-Acting Modulator of Fetal Hemoglobin?

PMID- 30227391
TI  - Ecdysone Elicits Chronic Renal Impairment via Mineralocorticoid-Like Pathogenic
      Activities.
AB  - BACKGROUND/AIMS: Ecdysteroids are steroidal insect molting hormones that also
      exist in herbs. Ecdysteroid-containing adaptogens have been popularly used to
      improve well-being and by bodybuilders for muscle growth. However, the use of
      ecdysone in mammals is also associated with kidney growth and enlargement,
      indications of disturbed kidney homeostasis. The underlying pathogenic mechanism
      remains to be clarified. METHODS: Virtual screening tools were employed to
      identify compounds that are homologous to ecdysone and to predict putative
      ecdysone-interacting proteins. The kidney effect of ecdysone was examined in
      vitro and in vivo and compared with that of aldosterone. Cellular apoptosis was
      estimated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Cell
      motility was assessed by scratch-wound cell migration assay. Blood urea nitrogen
      was measured to evaluate renal function. Western immunblot analysis was employed
      to determine the expression profile of interested proteins. RESULTS:
      Computational molecular structure analysis revealed that ecdysone is highly
      homologous to aldosterone. Moreover, virtual screening based on compound-protein
      interaction profiles identified the Mineralocorticoid Receptor (MR) to
      potentially interact with ecdysone. Accordingly, to assess potential biological
      functions of ecdysone in mammals, ecdysone was applied to mineralocorticoid
      sensitive inner medullar collecting duct cells. Ecdysone induced mesenchymal
      accumulation of extracellular matrix and epithelial dedifferentiation
      characterized by de novo expression of alpha-smooth muscle actin. In addition,
      ecdysone elicited cellular apoptosis and retarded cell motility, akin to the
      effect of aldosterone. In vivo, daily treatment of mice with ecdysone increased
      cell apoptosis in the kidney, impaired renal function and elicited early signs of
      renal fibrogenesis, marked by deposition of collagen and fibronectin in
      tubulointerstitium, reminiscent of the action of aldosterone. The MR signaling
      pathway is likely responsible for the cellular and pathobiological effects of
      ecdysone, as evidenced by strong ecdysone-induced MR nuclear translocation in
      renal tubular cells both in vitro and in vivo, while blockade of MR by
      concomitant spironolactone treatment largely abolished the detrimental effects of
      ecdysone. CONCLUSION: Our findings suggest that ecdysone induces
      mineralocorticoid-dependent activities that impair renal function and elicit
      renal injury.

PMID- 30227394
TI  - Efficacy of Recombinant Human Soluble Thrombomodulin in Treating Disseminated
      Intravascular Coagulation Complicating Allogeneic Hematopoietic Stem Cell
      Transplantation.
AB  - The prognosis for patients who experience hemostatic complications after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. However,
      no report has investigated disseminated intravascular coagulation (DIC) caused by
      the complications of allo-HSCT without infection. Recombinant human soluble
      thrombomodulin (rhTM) was used to treat 12 episodes of DIC (n = 10; group 1)
      caused by allo-HSCT complications such as acute graft-versus-host disease (aGVHD)
      or thrombotic microangiopathy (TMA), and the clinical outcomes were compared with
      those of historical controls (n = 9; group 2) treated for DIC without rhTM. In
      group 1, the mean DIC score was significantly improved after using rhTM.
      Fibrinogen degeneration product (FDP), C-reactive protein (CRP), and the
      inflammatory cytokine high-mobility group box 1 (HMGB1) were also significantly
      decreased. Serial changes from the baseline values of platelet counts and levels
      of FDP were significantly better in group 1 than in group 2. The recovery rate
      from DIC was significantly higher in group 1 than in group 2. These findings
      suggest that rhTM is effective against both DIC and systemic inflammatory
      complications after allo-HSCT.

PMID- 30227395
TI  - A National Document for Child Nutrition in Iran: A Vital Need.

PMID- 30227396
TI  - Short-Term High-Intensity Interval Training Is Superior to Moderate-Intensity
      Continuous Training in Improving Cardiac Autonomic Function in Children.
AB  - OBJECTIVES: This study aimed to investigate the impact of 3 isocaloric exercise
      programs on cardiac autonomic nervous system (ANS) functioning in children.
      METHODS: One hundred nine children (39% boys and 61% girls) aged 10-13 years
      (mean 11.07 +/- 0.81) were conveniently assigned to 1 of 4 groups as follows:
      Moderate-intensity continuous training (MICT; n = 29) at 65-70% of the predicted
      maximum heart rate (MHR), High-intensity interval training (HIIT; n = 29) at >
      80% of the predicted MHR, HIIT and MICT combined on alternate weeks (ALT; n =
      27), and a control group (n = 24). Morning ANS activity was assessed via analysis
      of heart rate variability (HRV), with the patient in supine position for 10 min,
      before and after the exercise intervention. DATA ANALYSIS: A 2-way analysis of
      variance was used to evaluate the effects of training on all HRV parameters (p <
      0.05/4 = 0.0125). RESULTS: After 5 weeks of training, significant improvements
      were observed for ln of the standard deviation of normal-to-normal intervals (p <
      0.0001), ln of the root mean square of successive difference (p < 0.0001), and ln
      of standard deviation 1 (p < 0.0001), with superior results reported in the HIIT
      group (effect size [ES] = 2.22, 2.69, and 2.69) compared with the MICT (ES =
      1.67, 1.75, and 1.75) and ALT (ES = 0.87, 1.06, and 1.06) groups, respectively.
      CONCLUSION: Short-term HIIT seems to induce superior alterations in cardiac ANS
      activity compared to MICT and ALT in children through enhanced vagal activity.

PMID- 30227397
TI  - Mediastinal Myeloid Sarcoma with TP53 Mutation Preceding Acute Myeloid Leukemia
      with a PICALM-MLLT10 Fusion Gene.
AB  - INTRODUCTION: Myeloid sarcoma (MS), previously known as granulocytic sarcoma or
      chloroma, is a rare neoplastic condition defined as a tumor mass consisting of
      myeloblasts or immature myeloid cells occurring at an extramedullary site.
      Clinical presentation is diverse and determined by a tumor mass effect or local
      organ dysfunction. CASE REPORT: We report the case of a 25-year-old previously
      healthy male with rapidly progressive shortness of breath. A chest CT scan
      demonstrated a heterogenous anterosuperior mediastinal mass with pleural and
      pericardial invasion. A diagnosis of MS with both myeloid and lymphoid
      characteristics was made by pathologic, morphologic, and immunophenotypic
      investigation. Next generation analysis revealed a pathogenic TP53 mutation
      (c.1035_1036insCT, p.Glu346Leufs*25). After 4 cycles of chemotherapy only a
      partial metabolic response and tumor size reduction was obtained. A pretransplant
      bone marrow biopsy revealed the progression of disease to acute myeloid leukemia.
      Cytogenetic analysis demonstrated a t(10; 11)(p12;q21). Fluorescence in situ
      hybridization confirmed the presence of a PICALM-MLLT10 fusion gene. CONCLUSION:
      MS with a mediastinal localization is rare and often misdiagnosed as malignant
      lymphoma. Acute leukemia harboring a PICALM-MLLT10 fusion gene is characterized
      by a mixed T cell and myeloid phenotype. The rearrangement is a rare recurrent
      translocation associated with specific clinical features, as illustrated in this
      case report.

PMID- 30227398
TI  - Real-Life Management of Children and Adolescents with Chronic Myeloid Leukemia:
      The Italian Experience.
AB  - BACKGROUND: To date, no data on the adherence to specific guidelines for children
      with chronic myeloid leukemia (CML) in chronic phase (CP) have been reported.
      METHODS: Since 2001, guidelines for treatment with imatinib mesylate (IM) and
      monitoring in patients younger than 18 years with CP-CML have been shared with 9
      pediatric referral centers (P centers) and 4 reference centers for adults and
      children/adolescents (AP centers) in Italy. In this study, the adherence to these
      guidelines was analyzed. RESULTS: Thirty-four patients with a median age of 11.4
      years and 23 patients with a median age of 11.0 years were managed at 9 P and at
      4 AP centers, respectively. Evaluations of bone marrow (BM) and/or peripheral
      blood (PB) were available for more than 90% of evaluable patients. Cytogenetics
      and molecular monitoring of PB were more consistently performed in AP centers,
      whereas molecular analysis of BM was carried out more frequently in P centers.
      Before 2009, some patients who responded to IM underwent a transplantation,
      contrary to the guidelines' recommendations. CONCLUSIONS: Our experience shows
      that having specific guidelines is an important tool for an optimal management of
      childhood CP-CML, together with exchange of knowledge and proactive discussions
      within the network.

PMID- 30227399
TI  - Rare Cause of Infantile Hypercalcemia: A Novel Mutation in the SLC34A1 Gene.
AB  - BACKGROUND: Under physiological conditions, proximal tubular phosphate
      reabsorption via NaPi-IIa (and NaPi-IIc) ensures the maintenance of phosphate
      homeostasis. Impairment of NaPi-IIa, encoded by SLC34A1, is associated with
      various overlapping clinical syndromes, including hypophosphatemic
      nephrolithiasis with osteoporosis, renal Fanconi's syndrome with chronic kidney
      disease, and idiopathic infantile hypercalcemia and nephrocalcinosis. METHODS: A
      patient was referred to our hospital due to hyponatremia, hyperkalemia, and
      hypophosphatemia, as well as persistent hypercalcemia after fluid therapy and
      sodium replacement. At admission to our hospital, potassium and sodium values
      were normal. After initiation of phosphorus therapy, hypokalemia and metabolic
      alkalosis were observed. Renal sonography showed bilateral medullary
      nephrocalcinosis. Analyses of the SLC34A1 gene were performed due to
      hypercalcemia and hypophosphatemia. RESULTS: Gene analyses identified a novel
      homozygous c.682T>C (p.W228R) (p.Trp228Arg) mutation. There are no previous
      reports of patients with SLC34A1 gene mutations presenting with hypokalemia and
      metabolic alkalosis. CONCLUSION: Herein, we present a case of infantile
      hypercalcemia 2 with a very different phenotype from that of previously described
      patients. Our findings provide further evidence for the wide range of phenotypic
      heterogeneity associated with NaPi-IIa impairment.

PMID- 30227400
TI  - Evaluation of Left Ventricular Performance: Is There a Gold Standard?

PMID- 30227401
TI  - Ophiopogonin D Reduces Myocardial Ischemia-Reperfusion Injury via Upregulating
      CYP2J3/EETs in Rats.
AB  - BACKGROUND/AIMS: Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase
      (CYP) metabolites of arachidonic acid and have multiple cardiovascular effects.
      Ophiopogonin D (OP-D) is an important effective monomeric component in Shenmai
      injection (SM-I). Both have been reported to have a variety of biological
      functions, including anti-inflammatory, anti-oxidant, and anti-apoptotic effects.
      We previously demonstrated that OP-D-mediated cardioprotection involves
      activation of CYP2J2/3 and enhancement of circulating EETs levels in vitro and
      can be developed as a novel drug for the therapy of myocardial ischemia
      reperfusion (MI/R) injury. We therefore hypothesized that the protective effects
      of OP-D and SM-I against MI/R injury are associated with increased expression of
      CYP2J3 and enhanced circulating 11,12-EET levels in vivo. METHODS: A rat model of
      MI/R injury was generated by ligation of the left anterior descending coronary
      artery for 40 min, followed by reperfusion for 2 h to determine the protective
      effects and potential mechanisms of OP-D and SM-I. Electrocardiogram and
      ultrasonic cardiogram were used to evaluate cardiac function; 2,3,5
      triphenyltetrazolium chloride was used to measure myocardial infarct size;
      hematoxylin and eosin staining and transmission electron microscopy were used to
      observe the morphology of myocardial tissue; and the expression of related
      proteins in the mechanistic study was observed by western blot analysis. RESULTS:
      We found that OP-D and SM-I exert protective effects on MI/R injury, including
      regulation of cardiac function, reduction of lactate dehydrogenase and creatine
      kinase production, attenuation of myocardial infarct size, and improvement of the
      recovery of damaged myocardial structures. We found that OP-D and SM-I activate
      CYP2J3 expression and increase levels of circulating 11,12-EET in MI/R-injured
      rats. CONCLUSION: We tested the hypothesis that the cardioprotective effects of
      OP-D and SM-I on MI/R injury are associated with increased expression of CYP2J3
      and enhanced circulating 11,12-EET levels in rats. Taken together, our results
      show that the effects of OP-D and SM-I were also mediated by the activation of
      the PI3K/Akt/eNOS signaling pathway, while inhibition of the NF-kappaB signaling
      pathway and antioxidant and anti-apoptotic effects were involved in the
      cardioprotective effects of OP-D and SM-I.

PMID- 30227402
TI  - Maximizing the Use of Scoring Systems in the Prediction of Outcomes in Acute
      Pancreatitis.
AB  - BACKGROUND/AIMS: No single classification system has so far effectively predicted
      the severity for Acute Pancreatitis (AP). This study compares the effectiveness
      of classification systems: Original Atlanta (OAC), Revised Atlanta (RAC),
      Determinant based classification (DBC), PANC 3, Harmless AP Score (HAPS),
      Japanese Severity Score (JSS), Symptoms Nutrition Necrosis Antibiotics and Pain
      (SNNAP), and Beside Index of Severity for AP (BISAP) in predicting outcomes in
      AP. METHODS: Scores for BISAP, Panc 3, HAPS, SNNAP, OAC, RAC, and DBC were
      calculated for 221 adult patients hospitalized for AP. Receiver Operating
      Characteristic curve analysis and Akaike Information Criteria were used to
      compare the effectiveness of predicting need for surgery, intensive care unit
      (ICU) admission, readmission within 30 days, and length of hospital stay.
      RESULTS: Both the RAC and the DBC strongly predict the length of hospital stay (p
      < 0.0001 for both) and ICU admission (p < 0.0001 for both). Additionally, both
      BISAP and PANC 3 showed weak predictive capacity at identifying length of stay
      and ICU admission. CONCLUSIONS: We suggest that BISAP and PANC3 be obtained
      within the initial 24 h of hospitalization to offer an early prediction of length
      of stay and ICU admission. Subsequently, RAC and DBC can offer further
      information later in the course of the disease.

PMID- 30227403
TI  - Disseminated Intravascular Coagulation Complicating Allogeneic Hematopoietic Stem
      Cell Transplantation.

PMID- 30227404
TI  - How to Define Acute Liver Failure Patients with Pre-Existing Liver Disease
      without Signs of Cirrhosis.
AB  - BACKGROUND: The definition of acute liver failure (ALF) usually implies no
      previous liver injury. Though, some patients admitted to liver transplantation
      centers with the diagnosis of ALF are obese or have diabetes. Elevated liver
      enzymes were not recorded previously, and no signs of cirrhosis or prior
      decompensation of the liver function were ever present. Still, these patients
      differ from the "typical" ALF-patient. GOALS: In this study, we aimed to confirm
      acute-on-chronic-liver failure (AOCLF) in patients diagnosed with ALF and to
      identify possible differences between ALF and AOCLF. STUDY: Patients were
      retrospectively recruited from all patients admitted to the University Hospital
      Essen with diagnosis of ALF between 2008 and 2015. Data of 163 patients were
      evaluated, resulting in a reclassification of 32 patients as AOCLF (remaining
      ALF: 131). Demographic and clinical data as well as serum parameters, including
      cell death markers, were correlated with clinical outcome. RESULTS: Patients with
      AOCLF were significantly older, had a higher body mass index (BMI), and were more
      often male. The cause for liver failure in these patients differed significantly
      from patients who had an actual ALF. Significant differences were also found for
      serum liver enzymes. Outcome of patients did not differ between AOCLF and ALF.
      Though, lower BMI and MELD and higher AST and GLDH were predictors for a
      beneficial outcome. CONCLUSION: AOCLF is still commonly misdiagnosed as ALF.
      While clinical outcome does not significantly differ between ALF and AOCLF, risk
      factors for adverse outcome may significantly differ between these entities.

PMID- 30227405
TI  - Microarray-Based Gene Expression Analysis Identifies Potential Diagnostic and
      Prognostic Biomarkers for Waldenstrom Macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is
      rare but a clinicopathologically distinct B-cell malignancy. This study assessed
      differentially expressed genes (DEGs) to identify potential WM biomarkers and
      uncover the underlying the molecular mechanisms of WM progression using gene
      expression profiles from the Gene Expression Omnibus database. DEGs were
      identified using the LIMMA package and their potential functions were then
      analyzed by using the gene ontology (GO) and Kyoto Encyclopedia of Genes and
      Genomes pathway enrichment analyses and the protein-protein interaction (PPI)
      network analysis by using the Search Tool for the Retrieval of Interacting
      Genes/Proteins database. Data showed that among 1,756 DEGs, 926 were upregulated
      and 830 were downregulated by comparing WM BM CD19+ with normal PB CD19+ B cell
      samples, whereas 241 DEGs (95 upregulated and 146 downregulated) were identified
      by comparing WM BM CD138+ with normal BM CD138+ plasma cell samples. The DEGs
      were enriched in different GO terms and pathways, including the apoptotic
      process, cell cycle arrest, immune response, cell adhesion, mitogen-activated
      protein kinase signaling pathway, toll-like receptor signaling pathway, and the
      gonadotropin-releasing hormone signaling pathway. Hub nodes in the PPI network
      included CDK1, JUN, CREBBP, EP300, CAD, CDK2, and MAPK14. Bioinformatics analysis
      of the GSE9656 dataset identified 7 hub genes that might play an important role
      in WM development and progression. Some of the candidate genes and pathways may
      serve as promising therapeutic targets for WM.

PMID- 30227407
TI  - Early Loss of Forkhead Transcription Factor, O Subgroup, Member 1 Protein in the
      Development of Pancreatic Ductal Adenocarcinoma.
AB  - OBJECTIVES: Forkhead transcription factor, O subgroup, member 1 (FOXO1) is a
      regulatory protein that plays an essential role in cellular homeostasis. A
      biological function as a tumor suppressor has been proposed. Here, we examined
      FOXO1 expression in human pancreatic ductal adenocarcinoma (PDAC) and its
      precursor lesions. METHODS: We immunohistochemically labeled tissue samples from
      47 patients with PDAC for FOXO1 protein. In addition, we extracted data from the
      Cancer Genome Atlas and the Cancer Cell Line Encyclopedia and studied a potential
      association with well-established genetic variants. A publicly available
      microarray dataset of 102 PDAC samples was used to explore the influence of FOXO1
      expression on patients' clinical outcome. RESULTS: Normal ductal epithelium
      universally expressed nuclear and cytoplasmic FOXO1. Reduced expression was
      observed in PanIN lesions and PDAC of all cases. Analysis of several datasets
      showed that the FOXO1 gene transcript levels do not correlate with KRAS, TP53,
      SMAD4, or CDKN2A mutation status, but positively correlate with patients'
      outcomes. CONCLUSIONS: Loss of FOXO1 protein is identified as an early event
      during PDAC development and may be independent of the top 4 mutated cancer genes.
      Because of its strong expression in normal ductal cells, immunohistochemical
      detection of FOXO1 can function as a valuable test to establish the diagnosis of
      transformation and malignancy in pancreatic tissues.

PMID- 30227408
TI  - Clinical Implication of Multi-Parameter Flow Cytometry in Myelodysplastic
      Syndromes.
AB  - Myelodysplastic syndromes (MDS) are a challenging group of diseases for
      clinicians and researchers, as both disease course and pathobiology are highly
      heterogeneous. In (suspected) MDS patients, multi-parameter flow cytometry can
      aid in establishing diagnosis, risk stratification and choice of therapy. This
      review addresses the developments and future directions of multi-parameter flow
      cytometry scores in MDS. Additionally, we propose an integrated diagnostic
      algorithm for suspected MDS.

PMID- 30227406
TI  - Early Hospital Readmission in Older and Younger Kidney Transplant Recipients.
AB  - BACKGROUND: Up to 31% of kidney transplant (KT) recipients experience early
      hospital readmission (EHR). We hypothesized that EHR among older KT recipients is
      higher than younger recipients due to increased comorbidities and higher
      prevalence of frailty. METHODS: We identified 22,458 older (age >=65) and 86,372
      younger (18 to < 65) first-time KT recipients (December 1, 1999 - December 31,
      2014) using United States Renal Data System data. We estimated the association
      between patient-level characteristics and EHR (30 days post-KT discharge) with
      modified Poisson regression among older and younger KT recipients, separately. We
      estimated the association between graft loss and mortality and EHR using Cox
      proportional hazards. RESULTS: EHR was more common in older KT recipients (30.1
      vs. 27.6%; p < 0.001). Risk factors for EHR that differed by recipient age
      included female sex, African American race, diabetes, smoking, dialysis vintage,
      donor age, and length of stay. Risk of graft loss associated with EHR was greater
      among older KT recipients (adjusted hazard ratio [aHR] 1.64, 95% CI 1.51-1.77, p
      < 0.001) than younger KT recipients (aHR 1.43, 95% CI 1.38-1.48, p < 0.001;
      interaction p < 0.01). However, the risk of mortality associated with EHR was
      greater among younger recipients (aHR 1.52, 95% CI 1.47-1.57, p < 0.001) than
      that in older -recipients (aHR 1.40, 95% CI 1.34-1.47, p < 0.001; interaction p <
      0.01). CONCLUSIONS: Older KT recipients are more likely to experience EHR and are
      at a higher risk of graft loss after EHR than younger recipients. Targeted
      interventions to prevent EHR and subsequent graft loss in this population should
      be identified.

PMID- 30227409
TI  - The Hospital and Patient Burden of Indwelling Pleural Catheters: A Retrospective
      Case Series of 210 Indwelling Pleural Catheter Insertions.
AB  - BACKGROUND: Indwelling pleural catheters (IPC) offer an alternative to talc
      pleurodesis in recurrent effusion, especially in patients wishing to avoid
      hospitalization. Two randomized trials have demonstrated reduced time in hospital
      using IPCs versus talc pleurodesis in malignant pleural effusion (MPE). However,
      the impact of IPCs on hospital services and patients has not been well studied.
      OBJECTIVES: To analyze long-term outcomes of IPCs and understand the hospital
      burden in terms of requirement for hospital visits and contacts with healthcare,
      while the IPC was in situ. METHODS: IPC insertions in a tertiary pleural center
      were analyzed retrospectively. Reviews of patients with IPCs in situ considered
      "additional" to routine clinical follow-up were defined pre-hoc. RESULTS: A total
      of 202 cases were analyzed: 89.6% MPE group (n = 181) and 10.4% non-MPE group (n
      = 21). There were a median 3.0 (interquartile range [IQR] 3) and 2.0 (IQR 2)
      ipsilateral pleural procedures prior to each IPC insertion in non-MPE and MPE
      groups, respectively (p = 0.26), and a mean 1.3 (SD 1.7) planned IPC-related
      outpatient follow-up visits per patient. There were 2 (9.5%) and 14 (7.7%) IPC
      related infections in non-MPE and MPE groups, respectively. Four (19.0%) and 44
      (24.3%) patients required additional IPC-related reviews in non-MPE and MPE
      groups, respectively (p = 0.6), and these occurred within 250 days post IPC
      insertion. CONCLUSIONS: Although IPCs decrease initial length of hospital stay
      compared to talc pleurodesis via chest drain, IPCs are associated with
      significant hospital-visit burden, in addition to planned visits and regular home
      IPC drainages. IPC-using services need to be prepared for this additional work to
      run an IPC service effectively.

PMID- 30227410
TI  - Melatonin Induces Osteoblastic Differentiation of Mesenchymal Stem Cells and
      Promotes Fracture Healing in a Rat Model of Femoral Fracture via Neuropeptide
      Y/Neuropeptide Y Receptor Y1 Signaling.
AB  - The function of melatonin (MLT) in promoting fracture healing has been
      demonstrated in previous studies. However, the molecular mechanism underlying
      therapeutic effects of MLT is not entirely clear. In this study, mesenchymal stem
      cells (MSCs) were isolated from rat bone marrow and identified by flow cytometry.
      We found that MLT treatment upregulated the neuropeptide Y (NPY) and NPY receptor
      Y1 (NPY1R) expression, and promoted the proliferation and migration of MSCs,
      which was suppressed by BIBP3226, an inhibitor of NPY1R. Moreover, the levels of
      NPY and NPY1R in MSCs undergoing osteoblastic differentiation were upregulated
      after MLT administration. MLT-induced osteoblastic differentiation of MSCs was
      suppressed by BIBP3226 treatment, as evidenced by decreased levels of alkaline
      phosphatase (ALP), collagen type I alpha1 chain, osteocalcin, and runt-related
      transcription factor 2, downregulated activity of ALP, as well as reduced calcium
      nodule formation. Furthermore, we demonstrated that MLT could promote fracture
      healing in a rat model of femoral fracture, which was accompanied by the elevated
      expression of NPY and NPY1R. The administration of BIBP3226 inhibited fracture
      healing mediated by MLT. To sum up, our results show that MLT promotes
      osteoblastic differentiation of MSCs and fracture healing by NPY/NPY1R signaling.

PMID- 30227411
TI  - Brief Report on 3-Weekly Paclitaxel Carboplatin Efficacy in Locally Advanced or
      Metastatic Squamous Vulvar Cancer.
AB  - In this brief report, we present our experience with 3-weekly paclitaxel
      carboplatin chemotherapy for patients with vulvar cancer. Two patients with
      locally advanced disease had an impressive response allowing standard vulvar
      cancer surgery. One patient with metastatic disease had local stable disease
      though it was progressive in the lymph nodes. The available literature is sparse
      and retrospective. Based on promising results, however, a prospective multicenter
      study is mandatory in order to obtain full data in a larger series of patients in
      order to learn the benefits of neoadjuvant paclitaxel-carboplatin and compare the
      results with chemoradiation.

PMID- 30227413
TI  - Spectrum of Ankyrin Mutations in Hereditary Spherocytosis: A Case Report and
      Review of the Literature.
AB  - BACKGROUND/AIMS: Hereditary spherocytosis (HS) is a common pediatric hemolytic
      anemia caused by congenital red blood cell defects. HS due to ankyrin 1 (ANK1)
      mutations is the most common type. We explored an ANK1 mutation from an HS
      patient and reviewed the literature. METHODS: We detected the mutation in a
      Chinese family in which 2 members were diagnosed with HS by next-generation
      sequencing. The proband was diagnosed with HS in the newborn period, based on
      clinical manifestations, laboratory data, and family history. The mutation
      spectrum of the ANK1 gene was summarized based on 85 patients diagnosed with HS
      carrying ANK1 mutations, and the ANK1 mutation spectrum was summarized and
      analyzed. RESULTS: We identified a novel mutation affecting ANK1 gene splicing (a
      splicing mutation) in both the patient and her mother, which is a substitution of
      T>G 2 nt after exon 25 in intron 26. The study expands our knowledge of the ANK1
      gene mutation spectrum, providing a molecular basis for HS. CONCLUSION: A novel
      ANK1 mutation (NM_000037.3, c.2960+2T>G, intron 26) that is potentially
      associated with HS was identified. To date, 80 ANK1 mutations have been reported
      to be associated with HS in humans.

PMID- 30227412
TI  - Physical Activity Level Assessed by Accelerometer and PAQ-C in Tunisian Children.
AB  - BACKGROUND: Physical activity (PA) is an important agent in the prevention of
      chronic diseases such as obesity. OBJECTIVES: To provide preliminary data on PA
      among school children and to correlate the PA with weight status. MATERIAL AND
      METHODS: A total of 40 children aged between 8 and 11 years and attending
      Tunisian schools were recruited. The body composition was determined by using the
      deuterium oxide dilution technique. PA was determined by the PAQ-C (PA
      Questionnaire for Older Children). An objective monitoring of PA and sedentary
      time was achieved by using ActiGraph GT3X + accelerometers. RESULTS: PAQ-C data
      demonstrate that 20% of the sample had light PA levels and 80% had moderate PA
      levels. Times spent in sedentary (62.37%) and light (30.80%) activities were
      higher than that spent in moderate and vigorous (6.83%) activities. Furthermore,
      almost half of the sample spent more than 60 min per day in moderate-to-vigorous
      intensity PA (MVPA). The average MVPA was significantly higher in normal weight
      than overweight and obese groups (67.68 +/- 20.98 vs. 49.07 +/- 19.09, p =
      0.007). The proportion of overweight children who spent more than 60 min per day
      in MVPA was significantly higher than that of normal-weight (60.9 vs. 29.4%; p =
      0.049). CONCLUSION: This study indicates that half of school children comply with
      the health-based guidelines for PA and sedentary behavior. Our findings also
      suggest that obesity was associated with decrease in PA in Tunisian children.

PMID- 30227414
TI  - Positive Airway Pressure to Enhance Computed Tomography Imaging for Airway
      Segmentation for Virtual Bronchoscopic Navigation.
AB  - RATIONALE: Virtual bronchoscopic navigation (VBN) guidance to peripheral
      pulmonary lesions is often limited by insufficient segmentation of the peripheral
      airways. OBJECTIVES: To test the effect of applying positive airway pressure
      (PAP) during CT acquisition to improve segmentation, particularly at end
      expiration. METHODS: CT acquisitions in inspiration and expiration with 4 PAP
      protocols were recorded prospectively and compared to baseline inspiratory
      acquisitions in 20 patients. The 4 protocols explored differences between devices
      (flow vs. turbine), exposures (within seconds vs. 15-min) and pressure levels (10
      vs. 14 cmH2O). Segmentation quality was evaluated with the number of airways and
      number of endpoints reached. A generalized mixed-effects model explored the
      estimated effect of each protocol. MEASUREMENTS AND MAIN RESULTS: Patient
      characteristics and lung function did not significantly differ between protocols.
      Compared to baseline inspiratory acquisitions, expiratory acquisitions after 15
      min of 14 cmH2O PAP segmented 1.63-fold more airways (95% CI 1.07-2.48; p =
      0.018) and reached 1.34-fold more endpoints (95% CI 1.08-1.66; p = 0.004).
      Inspiratory acquisitions performed immediately under 10 cmH2O PAP reached 1.20
      fold (95% CI 1.09-1.33; p < 0.001) more endpoints; after 15 min the increase was
      1.14-fold (95% CI 1.05-1.24; p < 0.001). CONCLUSIONS: CT acquisitions with PAP
      segment more airways and reach more endpoints than baseline inspiratory
      acquisitions. The improvement is particularly evident at end-expiration after 15
      min of 14 cmH2O PAP. Further studies must confirm that the improvement increases
      diagnostic yield when using VBN to evaluate peripheral pulmonary lesions.

PMID- 30227415
TI  - Treatment Effects in Retinal Angiomatous Proliferation Imaged with OCT
      Angiography.
AB  - PURPOSE: This prospective case series is aimed at exploring optical coherence
      tomographic angiography (OCT-A) as a treatment monitoring tool in patients
      treated for retinal angiomatous proliferation (RAP). METHODS: Twelve treatment
      naive RAP patients were included, with a median age of 79 years (range 65-90).
      Patients were imaged with an experimental 1,040-nm swept-source phase-resolved
      OCT-A instrument before and after treatment. Treatment consisted of either
      intravitreal bevacizumab or triamcinolone injections with or without photodynamic
      therapy (PDT). Abnormal blood flow after treatment was graded as increased,
      unchanged, decreased, or resolved. RESULTS: OCT-A images before and after
      treatment could be obtained in 9 patients. The median follow-up period was 10
      weeks (range 5-19). After various treatments, the RAP lesion resolved in 7
      patients, in 1 patient the OCT-A depicted decreased flow in the lesion, and 1
      patient showed unchanged abnormal blood flow. Monotherapy with intravitreal
      bevacizumab injections resolved RAP in 1 out of 2 patients. Combined therapy of
      bevacizumab with PDT resolved RAP in 6 out of 7 patients. CONCLUSIONS: OCT-A
      visualized resolution of abnormal blood flow in 7 out of 9 RAP patients after
      various short-term treatment sequences. OCT-A may become an important noninvasive
      monitoring tool for optimizing treatment strategies in RAP patients.

PMID- 30227417
TI  - Dental Caries in European Adults and Senior Citizens 1996-2016: ORCA Saturday
      Afternoon Symposium in Greifswald, Germany - Part II.
AB  - This review assesses the development of oral health habits and status in European
      adults (35-44 years old) and senior citizens (65-74 years old) over the period of
      1996-2016. There seem to be good opportunities for improving oral health habits
      by brushing twice daily with fluoride toothpaste among adults, as only 33-85%
      reported doing so. Caries experience was extensive among adults (>=92%). In
      adults of 23 countries, the mean DMFT score ranged from 6.6 to 17.6 (median
      12.1). In senior citizens of 21 countries, the mean DMFT score varied from 14.7
      to 25.5 (median 22.0). Repeated cross-sectional studies on caries trends in
      adults revealed a reduction of the DMFT value by 20%, referring to country-wide
      data. Among senior citizens, the corresponding reduction was 13%, with a shift in
      the DMFT components, i.e., with lower MT and higher FT scores. Edentulousness in
      the age group of 35- to 44-year-olds started disappearing in Europe from the year
      2000, and had been markedly reduced in some countries during the last decade.
      However, the eradication of edentulousness among 65- to 74-year-olds has not yet
      been reported. Further epidemiological surveys should apply caries diagnostic
      criteria that, besides representing our contemporary understanding of oral health
      care, allow comparisons with previous surveys using the WHO criteria. In
      conclusion, in the last two decades, a decline in caries was observed among
      European adults, and to a lesser extent among senior citizens. It is expected
      that the decline in caries will contribute to better oral health of individuals.

PMID- 30227418
TI  - Could Some Patients with Treatment-Resistant Schizophrenia Have Reversible
      Conditions?

PMID- 30227416
TI  - Hepatocyte Growth Factor Facilitates Esophageal Mucosal Repair and Inhibits the
      Submucosal Fibrosis in a Rat Model of Esophageal Ulcer.
AB  - BACKGROUND/AIMS: Esophageal mucosal damage often causes scar tissue, leading to
      refractory stricture. The aim of this study was to clarify the effect of
      hepatocyte growth factor (HGF) on esophageal mucosal repair and fibrosis leading
      to stricture in a rat model of esophageal ulcer. METHODS: Esophageal ulcers were
      induced in rats by topical exposure of the lower esophageal serosa to acetic
      acid, followed by intraperitoneal administration of HGF (200 ug/day) using an
      osmotic pump for 7 days. The effect of HGF on esophageal mucosal injury was
      investigated macroscopically and microscopically. The effect of HGF on epithelial
      cell proliferation and the expression of genes closely associated with the
      development of fibrosis were also examined. RESULTS: The administration of HGF
      for 7 days led to a significant reduction in the ulcerative area and enhanced the
      proliferation of esophageal epithelial cells. HGF treatment significantly
      decreased the fibrosis, and subsequently attenuated not only the foreshortening
      but also the narrowing of the esophagus. The expression levels of tissue
      inhibitor of metalloproteinase (TIMP)-1, -2, and matrix metalloproteinase (MMP)
      2, -9 were significantly decreased among rats treated with HGF. CONCLUSION: HGF
      facilitates the repair of esophageal mucosal injury and may also ameliorate the
      esophageal fibrosis, possibly through enhanced re-epithelization.

PMID- 30227419
TI  - Controversies among Cancer Registry Participants, Genomic Researchers, and
      Institutional Review Boards about Returning Participants' Genomic Results.
AB  - OBJECTIVES: Genomic information will increasingly be used to aid in the
      prevention, diagnosis, and treatment of disease. Several national initiatives are
      paving the way for this new reality, while also promoting new models of
      participant-engaged research. We compare the opinions of research participants in
      a cancer registry, human genetic researchers, and institutional review board
      (IRB) professionals about the return of individual-level genetic results (ROR).
      METHODS: Online surveys were administered to participants in a cancer registry (n
      = 450) and overlapping questions were compared to our previous online national
      surveys of human genetic researchers (n = 351) and IRB professionals (n = 208).
      RESULTS: The majority of respondents agreed that researchers have an obligation
      to return individual results when they would affect a participant's health. While
      77% of registry participants favored ROR if the researcher feels the participant
      might be interested in the results, only 30% of the IRB professionals and 25% of
      the genetic researchers agreed with this statement. CONCLUSIONS: Significant
      differences emerged between the stakeholder groups in several ROR scenarios.
      Policies that are acceptable to participants, researchers and IRBs, and that
      ensure human subject protections and facilitate research are needed.

PMID- 30227420
TI  - Survival after Endoscopic Valve Therapy in Patients with Severe Emphysema.
AB  - BACKGROUND: Endoscopic valve therapy leads to an improvement of lung function,
      exercise tolerance, and quality of life in a selected cohort of patients with
      advanced emphysema. So far, only few data exist on the long-term outcome.
      OBJECTIVES: This analysis evaluated the impact of valve therapy on the survival
      of emphysema patients. METHODS: Survival rates of emphysema patients who
      underwent valve therapy were assessed according to their radiological outcome
      following valve placement. RESULTS: From 2005 to 2013, 449 emphysema patients
      (mean age 64 +/- 7 years) underwent valve therapy and were followed for a mean
      time of 37.3 +/- 21.3 months. A total of 128 patients (29%) developed complete
      lobar atelectasis, 34 out of these also experienced a pneumothorax; 50 patients
      (11%) developed pneumothorax without lobar atelectasis, and 261 patients (58%)
      target lobe volume reduction or no volume change. Patients with atelectasis
      showed significantly better baseline forced expiratory volume in 1 second (%),
      residual volume (L), total lung capacity (L), and transfer factor for carbon
      monoxide (%; all p < 0.05), but there was no significant difference in the BODE
      score (p = 0.195). Patients with valve-induced lobar atelectasis had a
      significant survival benefit compared to patients without atelectasis (p = 0.009;
      5-year survival rate 65.3 vs. 43.9%). The advent of pneumothorax in 84 patients
      did not influence survival (p = 0.52). CONCLUSIONS: Lobar atelectasis following
      endoscopic valve therapy is associated with a survival benefit.

PMID- 30227421
TI  - Clinical and Pathological Challenges in the Diagnosis of Gastric-Type
      Differentiated Adenocarcinoma in the Stomach: A Study of Endoscopic Submucosal
      Dissection Cases.
AB  - BACKGROUND/AIMS: Gastric-type differentiated adenocarcinoma (GDA) of the stomach
      is a rare variant of gastric cancer that is highly infiltrating and exhibits
      early metastasis. However, the endoscopic and pathological features of "early
      stage" GDA remain unknown. The aim of this study is to characterize early-stage
      GDA. METHODS: We retrospectively enrolled 479 differentiated-type early gastric
      cancer cases who underwent endoscopic submucosal dissection (ESD). GDA cases were
      selected based on morphology and immunohistochemistry. Clinicopathological data
      were compared between gastric- and intestinal-type differentiated adenocarcinomas
      (IDAs). RESULTS: Thirteen lesions were classified as GDAs. GDAs as well as IDAs
      showed irregular microvascular and microsurface patterns with clear demarcation
      line on magnifying endoscopy with narrow band imaging (M-NBI). The rate of
      pathological misdiagnosis of GDAs in biopsy specimens was higher than that of
      IDAs (p = 0.016). GDA was significantly associated with positive lymphovascular
      invasion (p = 0.016). There was one intramucosal lesion with lymphatic invasion
      in GDA. CONCLUSIONS: Although M-NBI is useful to detect GDA, the pathological
      diagnosis of GDAs in biopsy specimens often remains challenging. When suspicious
      lesions are not diagnosed as GDA, they should be followed up intensively, or
      diagnostic ESD has to be performed. ESD specimens should be carefully evaluated
      because of a higher incidence of lymphovascular invasion.

PMID- 30227422
TI  - The Impact of Probiotic Supplements on Cognitive Parameters in Euthymic
      Individuals with Bipolar Disorder: A Pilot Study.
AB  - INTRODUCTION: Cognitive dysfunction is prevalent in depressive as well as manic
      episodes in individuals with Bipolar Disorder (BD). Even more, after symptom
      remission, many individuals with BD experience persisting cognitive impairment
      also in euthymic periods, leading to high illness burden and low quality of life.
      According to a recent research in animals and healthy humans, microbiota may
      influence cognitive processes via the brain-gut axis. A strategy to examine the
      role of the microbiota in different diseases is the intake of supplements that
      modulate the gut microbiome. The aim of this pilot study was to analyze the
      impact of probiotic supplements on cognitive parameters in a cohort of euthymic
      individuals with BD, receiving daily probiotic treatment over a time period of 3
      months. METHODS: A total of 20 euthymic individuals with BD received probiotic
      supplement over a time period of 3 months and completed a cognitive test battery
      at 3 time points (t1 at time of inclusion, t2 after one month and t3 after 3
      months of probiotic intake). RESULTS: We found a significant improvement of
      performance concerning attention and psychomotor processing speed measured with
      the Digit Symbol Test after one (t2) as well as after 3 months (t3) of treatment
      (F = 8.60; eta2 = 0.49, p < 0.01). Furthermore, executive function measured with
      the TMT-B, increased significantly over 3 months (F = 3.68; eta2 = 0.29, p <
      0.05). CONCLUSION: The results confirm the hypotheses that probiotic supplement
      might help stable individuals with BD to improve the cognitive function, which in
      turn might lead to better psychosocial, occupational, work and financial
      functioning. Nevertheless, the idea of this potential new treatment is
      challenging because of the variety of the human's gut microbiota.

PMID- 30227423
TI  - Breathing Hydrogen-Oxygen Mixture Decreases Inspiratory Effort in Patients with
      Tracheal Stenosis.
AB  - BACKGROUND: Hydrogen-oxygen mixture (H2-O2) may reduce airway resistance in
      patients with acute severe tracheal stenosis, yet data supporting the clinical
      use of H2-O2 are insufficient. OBJECTIVES: To evaluate the efficacy and safety of
      breathing H2-O2 in acute severe tracheal stenosis. METHODS: Thirty-five
      consecutive patients with severe acute tracheal stenosis were recruited in this
      prospective self-control study. Air, H2-O2 and O2 inhalation was given in 4
      consecutive breathing steps: air for 15 min, H2-O2 (6 L per min, H2:O2 = 2: 1)
      for 15 min, oxygen (3 L per min) for 15 min, and H2-O2 for 120 min. The primary
      endpoint was inspiratory effort as assessed by diaphragm electromyography
      (EMGdi); the secondary endpoints were transdiaphragmatic pressure (Pdi), Borg
      score, vital signs, and impulse oscillometry (IOS). The concentration of H2 in
      the ambient environment was obtained with 12 monitors. Adverse reactions during
      the inhalation were recorded. RESULTS: The mean reduction in the EMGdi under H2
      O2 was 10.53 +/- 6.83%. The EMGdi significantly decreased during 2 H2-O2
      inhalation steps (Steps 2 and 4) compared with air (Step 1) and O2 (Step 3)
      (52.95 +/- 15.00 vs. 42.46 +/- 13.90 vs. 53.20 +/- 14.74 vs. 42.50 +/- 14.12% for
      Steps 1 through 4, p < 0.05). The mean reduction in the Pdi under H2-O2 was 4.77
      +/- 3.51 cmH2O. Breathing H2-O2 significantly improved the Borg score and
      resistance parameters of IOS but not vital signs. No adverse reactions occurred.
      H2 was undetectable in the environment throughout the procedure. CONCLUSIONS:
      Breathing H2-O2 may reduce the inspiratory effort in patients with acute severe
      tracheal stenosis and can be used for this purpose safely.

PMID- 30227424
TI  - Biochemical and Morphological Characterization of a Neurodevelopmental Disorder
      Related Mono-ADP-Ribosylhydrolase, MACRO Domain Containing 2.
AB  - MACRO Domain Containing 2 (MacroD2) is a neurodevelopmental disorder-related mono
      ADP-ribosylhydrolase. Molecular features of this protein in neural tissues are
      largely unknown. In this study, we generated a specific antibody against MacroD2,
      and carried out expression and morphological analyses of the molecule during
      mouse brain development. In Western blotting, 2 MacroD2 isoforms with molecular
      masses of ~70 and ~75 kDa started to be expressed at embryonic day 16.5, reached
      the maximal level at postnatal day 8, and then gradually decreased through P30.
      In contrast, other isoforms with molecular masses of ~110 and ~140 kDa gradually
      increased during embryonic to postnatal development. In immunohistochemical
      analyses, MacroD2 was strongly detected in cortical neurons in layer II-V at P0
      and P7, while the protein expression decreased significantly in the neurons at
      P30. Immunofluorescence analyses revealed that MacroD2 was mainly distributed in
      the soma and to a lesser extent in the axon and dendrite of immature primary
      cultured mouse hippocampal neurons. On the other hand, in the matured hippocampal
      neurons, while MacroD2 was detected in the soma, it displayed in dendrites a
      punctate distribution pattern with a partial colocalization with synaptic
      markers, synaptophysin, and PSD95. The obtained results indicate that MacroD2 is
      expressed and may have a physiological role in the central nervous system during
      brain development.

PMID- 30227425
TI  - Expanding the Boundaries of Combined Renal Replacement Therapy for Non-Renal
      Indications.
AB  - Over the last decades, there have been major advancements in the field of renal
      replacement therapy (RRT) with utilization of newer technologies and advent of
      various modalities. Once exclusively used for treatment of renal failure and its
      metabolic consequences, the science of RRT has expanded to include non-renal
      indications such as treatment of fluid overload in patients with refractory heart
      failure. Hepatic encephalopathy due to sudden rise in serum ammonia level in the
      setting of acute liver failure represents an underexplored area in which RRT can
      potentially be helpful. While the key role of hyperammonemia in the pathogenesis
      of hepatic encephalopathy in patients with liver failure is well established,
      emerging data points to distinct pathophysiologic mechanisms underlying chronic
      alterations in neural metabolic functions and acute changes in cerebral
      perfusion. In the acute setting, ammonia can cross the blood-brain barrier at
      high levels leading to sudden formation of strong osmolytes, significant
      transcellular shift of water, and cerebral edema. Herein, we provide a brief
      overview of the role of RRT in management of acute hyperammonemia in the setting
      of acute liver failure and discuss the practical aspects of the available
      therapeutic modalities. Larger studies are needed to shed light on a number of
      clinical aspects such as the impact on the outcomes, criteria for selection of
      the patients that would benefit most from this therapeutic approach, optimal
      timing of initiation of RRT, and the most appropriate modality.

PMID- 30227426
TI  - Decision Making Criteria in Oncology.
AB  - Decision making is one of the most complex skills required of an oncologist and
      is affected by a broad range of parameters. For example, the wide variety of
      treatment options, with various outcomes, side-effects and costs present
      challenges in selecting the most appropriate treatment. Many treatment choices
      are affected by limited scientific evidence, availability of therapies or patient
      specific factors. In the decision making process, standardized approaches can be
      useful, but a multitude of criteria are relevant to this process. Thus, the aim
      of this review is to summarize common types of decision criteria used in oncology
      by focusing on 3 main categories: criteria associated with the decision maker
      (both patient and doctor), decision specific criteria, and the often-overlooked
      contextual factors. Our review aims to highlight the broad range of decision
      criteria in use, as well as variations in their interpretation.

PMID- 30227427
TI  - Geographic Hematology: Some Observations in Mexico.
AB  - In 1963 Jean Bernard introduced the concept of "geographic hematology" and
      distinguished 2 branches, i.e., "ethnic hematology," which deals with differences
      between populations, and "environmental hematology," which considers factors such
      as food habits, infections, and others. Both of these branches have implications
      in the distribution of hematological diseases worldwide. In comparison with
      Caucasian populations, in Mexico a significantly higher prevalence of acute
      lymphoblastic, acute promyelocytic, and acute megakaryoblastic leukemias has been
      described. The rate of chronic myeloid leukemia seems to be as high as that
      reported in Caucasian populations, while other myeloproliferative neoplasias are
      significantly less frequent in Mexico. Significantly lower prevalences of hairy
      cell leukemia, chronic lymphocytic leukemia, multiple myeloma, and Waldenstrom's
      macroglobulinemia have been reported from Mexico. Regrettably, the influence of
      drug companies interested in selling their new and expensive drugs has resulted
      in both overdiagnosis of some diseases and overidentification of the refractory
      forms of some of these conditions to justify the use of unnecessary drugs.

PMID- 30227428
TI  - Impaired Skin Barrier Function and Downregulated Expression of Caspase-14 in
      Moderate to Severe Chronic Hand Eczema.
AB  - AIM: To investigate whether the skin barrier function is impaired with regard to
      the pH value, water content, transepidermal water loss (TEWL), and the integrity
      of the stratum corneum, and whether the expression of caspase-14 is altered in
      moderate to severe chronic hand eczema (CHE). METHODS: Thirty patients with
      moderate to severe CHE treated at our institute and 30 healthy volunteers were
      included in this study. The pH value, water content, TEWL, and the integrity of
      the stratum corneum were measured in all subjects. RESULTS: Significantly
      increased pH value, decreased water content, elevated TEWL, and impaired
      integrity of the stratum corneum were observed in the lesional skin of CHE
      patients compared with the nonlesional skin of CHE patients and the normal skin
      of healthy volunteers. The expression of caspase-14 decreased in the lesional and
      nonlesional skin of CHE patients compared with the normal skin of healthy
      volunteers, especially prominent in the nonlesional skin. The mean optical
      density (OD) value of immunohistochemical staining for caspase-14 was
      significantly lower in the nonlesional skin than in the lesional skin and normal
      skin (p < 0.01 for both). Although the mean OD value was lower in the lesional
      skin than in the normal skin, the difference was not statistically significant (p
      > 0.05). CONCLUSION: Skin barrier dysfunction indeed occurs in CHE patients,
      which may be related to mechanisms associated with a downregulated expression of
      caspase-14.

PMID- 30227429
TI  - Medical Expulsive Therapy for Symptomatic Distal Ureter Stones: Is the
      Combination of Bromelain and Tamsulosin More Effective than Tamsulosin Alone?
      Preliminary Results of a Single-Center Study.
AB  - OBJECTIVES: To assess the safety and efficacy of bromelain plus tamsulosin versus
      tamsulosin alone as medical expulsive therapy (MET) for promoting spontaneous
      stone passage (SSP) of symptomatic distal ureter stones. PATIENTS AND METHODS:
      One-hundred-fourteen patients with a 4-10 mm distal ureteral stone were enrolled
      (Group A). Patients self-administered daily bromelain with tamsulosin for 30 days
      or until SSP or intervention was mandatory. Patients were compared to those from
      a control group taking tamsulosin as MET (Group B) and matched for the following
      factors: sex, age +/-10%, stone diameter. A logistic regression model evaluated
      bromelain and the ureteral stone diameter as explanatory variables. RESULTS: SSP
      rates were 87.7 vs. 75.4% for group A vs. group B respectively (p = 0.016); with
      no difference observed for the time to self-reported stone expulsion (11.68 vs.
      11.57 days; p = 0.91). Considering larger stones (> 5 mm), the SSP rate was 83.3%
      in group A and 61% in group B (p < 0.01). With each millimeter increment of stone
      diameter, the probability of SSP decreased by 59.1% (p < 0.0001), while it
      increased of 3.3 when bromelain was present. Only 3 cases of tamsulosin-related
      adverse events were recorded. CONCLUSION: The association of bromelain and
      tamsulosin as MET increases the probability of SSP of symptomatic distal ureteral
      stones, with no bromelain-related side effects recorded.

PMID- 30227430
TI  - Identification of Predictors of Recurrence in Patients with Lower Rectal Cancer
      Undergoing Neoadjuvant Chemotherapy: A Direct Comparison of Short-Course and Long
      Course Chemoradiotherapy.
AB  - OBJECTIVE: This study aimed to investigate clinicopathological responses and
      oncological outcome in patients receiving short- or long-course chemoradiotherapy
      (CRT) and to assess the predictive factor for recurrence in each treatment.
      METHODS: A total of 118 rectal cancer patients receiving preoperative CRT were
      enrolled. Clinicopathological responses and oncological outcome in patients
      receiving short- or long-course CRT were investigated. RESULTS: Despite there
      being no significant differences in the prognosis of disease-free survival (DFS)
      based on TNM stage classification in patients receiving long-course CRT, patients
      with advanced stage demonstrated poor DFS after short-course CRT. The presence of
      lymph node metastasis was a predictor of poor DFS in short-course CRT, whereas
      poor pathological response was a predictor of recurrence in long-course CRT.
      CONCLUSIONS: Distinct predictors of recurrence depending on the CRT course might
      be needed to discriminate candidates from rectal cancer patients receiving
      preoperative CRT who might benefit from more intensive adjuvant therapy after
      surgery.

PMID- 30227431
TI  - Deciphering the Lung Microbiome: Implications for Lung Health and Disease.

PMID- 30227432
TI  - High Enhancement Settings for White Light Observation Improves Colorectal Polyp
      Visibility in Color Difference Value and an Endoscopist's Visibility.
AB  - BACKGROUND/AIMS: Settings of structure and color enhancement (CE) change view of
      white light imaging and a preset low enhancement setting is used regularly. The
      aim of this study was to investigate whether higher enhancement settings
      increased colorectal lesions' visibility with endoscopists' visibility scoring
      and objective color difference (CD) value. METHODS: From April 2015 to September
      2015, we analyzed 27 pictures and 100 videos of colorectal lesions. Combinations
      of structure enhancement (B3, A3, A5) and CE (CE 0, 1, 3) were evaluated and CD
      values of 2 corresponding modes (high enhancement: A5 + CE3, preset low
      enhancement: A3 + CE0) were calculated using marketed software. In the video,
      these 2 modes were evaluated. All pictures and movies were graded by 4
      endoscopists using visibility scores: score 4 (excellent) to score 1 (poor).
      RESULTS: The scores of A3 + CE0 (2.74 +/- 1.09) were significantly lower than
      those of all other higher enhancement settings such as B3 + CE1 (3.11 +/- 1.08),
      A3 + CE1 (3.33 +/- 0.91), and A5 + CE3 (3.56 +/- 0.74; p < 0.001). The CD value
      of A5 + CE3 was significantly higher than A3 + CE0 (20.2 +/- 6.9 vs. 12.9 +/-
      5.6, p < 0.001). In the video, the scores for A5 + CE3 were significantly higher
      than A3 + CE0 (3.27 +/- 0.83 vs. 2.53 +/- 1.05, p < 0.001). CONCLUSIONS: Higher
      enhancement settings increased visibility of colorectal lesions.

PMID- 30227433
TI  - LABA/LAMA Fixed Dose Combination in Chronic Obstructive Pulmonary Disease: The
      Impact on Health-Related Quality of Life.
AB  - BACKGROUND: While fixed dose combinations (FDCs) of long-acting beta 2-agonists
      (LABAs) and long-acting muscarinic antagonists (LAMAs) are increasingly tested on
      their efficacy in improving lung function, their effectiveness on Patient
      Reported Outcomes (PROs) such as Health Related Quality of Life (HRQoL) and
      Health Status (HS) deserve more attention. OBJECTIVES: To review current
      available evidence about the treatment effect of fixed LABA/LAMA FDCs on HRQoL.
      METHODS: A systematic literature search for randomized controlled trials (RCTs)
      about the impact of LABA/LAMA FDCs versus placebo, LABA or LAMA or LABA/ICS on
      HRQoL in Chronic obstructive pulmonary disease (COPD) patients has been
      performed. RESULTS: Twenty-eight RCTs (n = 32, 165 COPD patients) investigating
      the impact of fixed LABA/LAMA combinations on HRQoL were included. Using the St
      George' s Respiratory Questionnaire, 27 out of 28 trials assessed HRQoL.
      LABA/LAMA FDCs significantly improved HRQoL versus placebo in 9 out of 11 trials,
      while change when compared to other LABA or LAMA monocomponents was significantly
      better in 11 out 24. In 5 out of 6 RCTs having LABA/ICS as comparators, LABA/LAMA
      FDC had a similar effect and only 1 showed significant improvement in HRQL
      compared to LABA/ICS FDC. CONCLUSION: LABA/LAMA FDCs may be helpful in improving
      HRQoL, but because of the heterogeneity of performed trials, strong conclusions
      cannot be drawn. Moreover, due to the different molecule properties, treatment
      schedule, and device characteristics of each FDC, a generalized judgment seems
      inappropriate. Pragmatic trials powered to detect real-life differences in HRQoL
      and head-to-head comparison are needed to guide clinical practice in terms of
      PROs.

PMID- 30227434
TI  - Towards an Organ-Sparing Approach for Locally Advanced Esophageal Cancer.
AB  - BACKGROUND: Active surveillance after neoadjuvant therapies has emerged among
      several malignancies. During active surveillance, frequent assessments are
      performed to detect residual disease and surgery is only reserved for those
      patients in whom residual disease is proven or highly suspected without distant
      metastases. After neoadjuvant chemoradiotherapy (nCRT), nearly one-third of
      esophageal cancer patients achieve a pathologically complete response (pCR). Both
      patients that achieve a pCR and patients that harbor subclinical disseminated
      disease after nCRT could benefit from an active surveillance strategy. SUMMARY:
      Esophagectomy is still the cornerstone of treatment in patients with esophageal
      cancer. Non-surgical treatment via definitive chemoradiotherapy (dCRT) is
      currently reserved only for patients not eligible for esophagectomy. Since
      salvage esophagectomy after dCRT (50-60 Gy) results in increased complications,
      morbidity and mortality compared to surgery after nCRT (41.4 Gy), the latter
      seems preferable in the setting of active surveillance. Clinical response
      evaluations can detect substantial (i.e., tumor regression grade [TRG] 3-4)
      tumors after nCRT with a sensitivity of 90%, minimizing the risk of development
      of non-resectable recurrences. Current scarce and retrospective literature
      suggests that active surveillance following nCRT might not jeopardize overall
      survival and postponed surgery could be performed safely. Key Message: Before an
      active surveillance approach could be considered standard treatment, results of
      phase III randomized trials should be awaited.

PMID- 30227435
TI  - Conservation of Ovary-Specific Genes, Foxl2, Aromatase, and Rspo1, in the Common
      Indian Garden Lizard, Calotes versicolor, That Lacks Chromosomal or Temperature
      Dependent Sex Determination.
AB  - Foxl2,Rspo1, and Aromatase are genes important in the ovary developmental pathway
      in mammals and birds. Here, we show their presence in the lizard, Calotes
      versicolor, which is known to lack a chromosomal as well as a temperature
      dependent mode of sex determination and has an indeterminate, bipotential gonad
      throughout embryonic development. The expression of the 3 genes, as well as that
      of CvSox9 and Wnt4 - the known testis and ovary pathway genes - was studied by RT
      PCR and whole tissue RNA in situ hybridization (WRISH) on the developing
      mesonephros gonadal complex (MGC). The expression of all 3 genes was initiated in
      the gonad shortly after its evagination from the mesonephros (day 5 onwards).
      CvFoxl2 generally was expressed in those MGCs in which CvSox9 was either not
      expressed or lowly expressed and vice versa. On the other hand, CvArom was
      expressed rather sporadically and randomly, showing no association with CvFoxl2,
      CvRspo1, or CvSox9, though in later stages WRISH preparations showed its
      coincidence with CvWnt4. CvRspo1 was expressed in almost all embryos right from
      day 5. Immunofluorescence localization of Rspo1 and Foxl2 proteins showed their
      presence in the gonads from day 10 onwards, and by day 25 it was primarily
      confined to the cortex but away from the coelomic epithelium of the gonadal
      cortex. Apparently both proteins were localized in the pregranulosa cells, Rspo1
      in the cytoplasm and Foxl2 in the nucleus. Thus, it is clear that both CvFoxl2
      and CvRspo1 are active in ovary formation, but whether they are expressed in the
      same or different cells is unknown. Though the transcription pattern of CvArom
      remains circumspect for its role in differentiation of the ovary, earlier
      evidence on aromatase inhibitor-induced reversal to the male sex indicates its
      importance in ovary function.

PMID- 30227436
TI  - The Female Genital Mutilation/Cutting Experience in Somali Women: Their Wishes,
      Knowledge and Attitude.
AB  - BACKGROUND: Female genital mutilation/cutting (FGM/C) is a common sociocultural
      practice in many communities in Africa. Unfortunately, what females are forced to
      accept because they are helpless, in order to be an individual in social life and
      in the country they live in, is an important health issue that is not only
      harmful to the human body but also against human rights. OBJECTIVES: This study
      aimed to investigate the wishes, knowledge and attitude of Somali women regarding
      FMG/C. METHODS: From 16 regions of Somalia, 356 women were randomly selected. A
      structured and interviewer-administered questionnaire was used to collect data.
      RESULTS: Except for one, all women participating in the survey were circumcised.
      A significant proportion of women embraced the continuation of FGM/C (52%) and
      54.2% of them were satisfied with being FMG/C. Their knowledge, attitude, and
      practices were shaped by their religion and traditions. However, the proportion
      of those who wanted to stop FGM/C was 91%. CONCLUSIONS: Further efforts and
      research from different countries, cultures, beliefs, organizations, and
      individuals focusing on knowledge, awareness, legalization, and the opinions of
      lay and religious individuals, particularly including women's rights activists,
      and women with FGM/C, are needed to stop FGM/C, also known as female
      circumcision.

PMID- 30227437
TI  - Are There Differences in Toxicity and Efficacy between Various Bacillus Calmette
      Guerin Strains in Bladder Cancer Patients? Analysis of 844 Patients.
AB  - PURPOSE: To evaluate if there are differences in toxicity and efficacy between
      different Bacillus Calmette-Guerin (BCG) stains used for intravesical
      immunotherapy in patients with non-muscle invasive bladder cancer. METHODS: We
      retrospectively analysed a group of 844 patients who received TICE, RIVM and
      Moreau BCG strains. The allocation of the strain to each patient was random,
      stemming from differences in supply and distribution. The patients were analysed
      in terms of toxicity, recurrence-free (RFS), progression-free (PFS), cancer
      specific (CSS) and overall survival (OS). RESULTS: In the survival analysis,
      statistical significance was not reached in any tumour group for any clinical
      event. TICE caused more local and mild adverse effects and severe complications
      were mainly associated with RIVM strain. In a group in which the strain was
      changed during the course of the therapy, significantly more severe complications
      were observed and, in most of these cases, complications appeared right after the
      strain change. CONCLUSIONS: There were no differences in terms of RFS, PFS, CSS
      and OS after use of TICE, RIVM and Moreau strains. The complication profile
      differed statistically between used strains with TICE causing mostly mild
      complications. Also, strain change during the therapy course was associated with
      the increased risk of moderate to severe toxicity occurrence.

PMID- 30227438
TI  - MPT0B169 and MPT0B002, New Tubulin Inhibitors, Induce Growth Inhibition, G2/M
      Cell Cycle Arrest, and Apoptosis in Human Colorectal Cancer Cells.
AB  - We previously synthesized new tubulin inhibitors, MPT0B169 and MPT0B002, which
      induced growth inhibition and apoptosis in leukemia cells. However, their effects
      on solid tumor cells have not been determined. In this study, we investigated the
      effects of MPT0B169 and MPT0B002 on glioblastoma, breast, lung, and colorectal
      cancer (CRC) cell lines. A cell viability analysis showed that MPT0B169 and
      MPT0B002 were more effective in inhibiting the proliferation of COLO205 and HT29
      CRC cells than U87MG and GBM8401 glioblastoma, MCF-7 and MDA-MB-231 breast
      cancer, and A549 lung cancer cells. MPT0B169 and MPT0B002 inhibited growth of
      COLO205 and HT29 cells in dose- and time-dependent manners. A colony-formation
      assay confirmed the growth inhibitory effects of MPT0B169 and MPT0B002 on COLO205
      and HT29 cells. MPT0B169 and MPT0B002 disrupted tubulin polymerization and
      arrested the cell cycle at the G2/M phase, with a concomitant increase of the
      cyclin B1 level. MPT0B169 and MPT0B002 induced apoptosis, accompanied by
      induction of the intrinsic apoptotic pathway, as shown by a reduction in the
      caspase-9 level and increases in cleaved caspase-3 and cleaved PARP. These
      results suggest that MPT0B169 and MPT0B002, new tubulin inhibitors, induced
      growth inhibition, G2/M arrest, and apoptosis in COLO205 and HT29 cells, and they
      could potentially be anticancer agents for CRC cells.

PMID- 30227439
TI  - Extended Techniques of Minimally Invasive Surgery in the Retroperitoneum:
      Practice Pattern in German Urology Departments.
AB  - INTRODUCTION: Laparoendoscopic single-site surgery (LESS), robot-assisted (RA),
      and retroperitoneoscopic (R) surgery expand the armamentarium of minimally
      invasive surgery (MIS). As information on the use of these surgical approaches in
      daily routine is limited, we conducted a survey among German urologists.
      MATERIALS AND METHODS: In 2017, all urology departments in Germany received a
      questionnaire evaluating practice patterns of MIS in the retroperitoneum. Chi
      Square test was performed for statistical analyses. The response rate was 51.1%
      (162/311) including 23 universities. RESULTS: R adrenalectomy and (partial)
      nephrectomy are performed by 32.7-40.1% of all departments. Transperitoneal LESS
      adrenalectomy and nephrectomy are performed by 8.6-11.7%. Retroperitoneal RA
      adrenalectomy and (partial) nephrectomy are performed by 6.2-13.0%. There was no
      difference in the R and LESS approach between (non)-university departments.
      Retroperitoneal RA access is more frequently used in university hospitals (all p
      < 0.01). If performed, mean counts within the last 12 months were < 5 for R,
      LESS, and RA adrenalectomy; and < 20 for R, LESS, and RA (partial) nephrectomy.
      CONCLUSION: Our survey provides a detailed insight into MIS in the
      retroperitoneum in German urology departments. Numbers of adrenalectomies as well
      as R, transperitoneal LESS and retroperitoneal RA procedures are low.
      Retroperitoneal RA surgery is more common in universities. Comprehensively, our
      survey proves that these approaches are not standard approaches yet.

PMID- 30227440
TI  - Combined Unilateral Posteroventral Pallidotomy and Ventral Intermediate Nucleus
      Thalamotomy in Tremor-Dominant Parkinson&apos;s Disease versus Posteroventral
      Pallidotomy Alone: A Prospective Comparative Study.
AB  - BACKGROUND: The optimum target in surgery for Parkinson's disease (PD) is still
      controversial, especially in patients with tremor-dominant PD. We aim to compare
      results in tremor-dominant patients undergoing pallidotomy vs. those undergoing
      simultaneous posteroventral pallidotomy (PVP) and ventral intermediate nucleus
      (VIM) thalamotomy. METHODS: Twenty-four patients with tremor-dominant PD were
      included in this study. Twelve patients received unilateral PVP contralateral to
      the most affected side. The other 12 patients received simultaneous unilateral
      PVP and VIM thalamotomy contralateral to the most affected side. Assessment of
      results in both groups was achieved using both UPDRS "off" motor scores and UPDRS
      rest tremor subscores. RESULTS: The mean UPDRS off motor score improved in the
      pallidotomy group from 61.3 preoperatively to 36.8 at 12 months. In the combined
      group, it improved from 59.6 to 35.2 at 12 months, with no statistically
      significant difference between both groups. On the other hand, while the mean
      tremor subscore in the pallidotomy group improved from a mean of 2.3-0.8, the
      tremors were abolished in all of the patients in the combined group except for 1
      patient who showed slight infrequent tremors at 12 months. CONCLUSION: Patients
      with tremor-dominant PD achieve more improvement in tremor control after combined
      PVP and VIM thalamotomy.

PMID- 30227441
TI  - Blood Pressure Variability in Acute Ischemic Stroke: The Role of Early
      Recanalization.
AB  - We performed a retrospective study with the aim of investigating the association
      between blood pressure (BP) variability in the first 24 h after ischemic stroke
      and functional outcome, regarding arterial recanalization status. A total of 674
      patients diagnosed with acute stroke and treated with revascularization therapies
      were enrolled. Systolic and diastolic BP values of the first 24 h after stroke
      were collected and their variation quantified through standard deviation.
      Recanalization state was evaluated at 6 h and clinical outcome at 3 months was
      assessed by modified Rankin Scale. In multivariate analyses systolic BP
      variability in the first 24 h post-stroke showed an association with 3 months
      clinical outcome in the whole population and non-recanalyzed patients. In
      recanalyzed patients, BP variability did not show a significant association with
      functional outcome.

PMID- 30227442
TI  - Copy Number Alterations with Prognostic Potential in Clear Cell Renal Cell
      Carcinoma.
AB  - OBJECTIVES: To detect chromosomal aberrations in a genome-wide manner with
      potential value for prognosis in groups of patients with different
      histopathological grading in clear cell renal carcinoma (ccRCC). MATERIAL AND
      METHODS: We performed a copy number alteration analysis using the Affymetrix
      platform and SNP 6.0 mapping arrays with samples from 48 ccRCC-patients. The data
      analysis was done using 3 different Software Platforms: Affymetrix Genotyping
      Console (version 4.1.3.840) and 2 open-source packages for validation: PennCNV
      and PICNIC. RESULTS: Consistent changes were found to divide the tumors into 4
      groups: first group showed typical losses on 3p, second group losses on 3p plus
      gains on 5q, third group gains on chromosome 7 plus losses on chromosome 8;
      fourth group did not show any major changes. We selected the affected genes with
      the highest consistency and identified 13 different genes mapping in the SNP 6.0
      results and Kyoto Encyclopedia of Genes and Genomes. Remarkable for further
      consideration were the phosphatidylinositol 3-kinase pathway, BRAF, MET, EGLN1;
      growth factors, for example, HGF, PGF and TGFB2. CONCLUSION: A multimodal
      approach with a well-defined workflow for detecting genomic aberrations by using
      array technologies and comparing the findings with different comprehensive
      databases may provide insights into functional tumor processes and help to
      identify potential new targets for more individualized future treatment.

PMID- 30227443
TI  - Transurethral Enucleation of Bladder Leiomyoma: A Series of Six Cases and Review
      of the Literature.
AB  - OBJECTIVES: To investigate the feasibility and initial surgical outcomes of
      transurethral enucleation for 6 patients with bladder leiomyoma. MATERIALS: Six
      patients (mean age 50.2, range [34-67]) with bladder leiomyoma underwent
      transurethral enucleation. In each case, the resectoscope was inserted into the
      bladder. A resecting loop was used to incise the urothelium along the surgical
      margin of the bladder tumor, and a push was given through the resecting loop to
      further separate the tumor until it was shelled off the bladder wall. The intact
      mass was then cut into pieces and flushed out. After the operation, irrigation
      therapy was given. RESULTS: Surgery was performed successfully in all 6 patients.
      The mean size of the tumor was 3.9 cm (1.8-6.7 cm). The mean operation time was
      60 min (30-100 min). The mean follow-up period was 14.8 months (2-30 months), and
      no evidence of recurrence was found in all cases. CONCLUSION: Transurethral
      enucleation is a safe, reliable, and effective surgical technique for selected
      patients with well-encapsulated tumors and is well suited for further
      pathological diagnosis and radical treatment.

PMID- 30227444
TI  - Diagnostic and Outcome Prediction Value of Transthoracic Impedance Cardiography
      in Heart Failure Patients During Heart Failure Flare-Ups.
AB  - BACKGROUND This study aimed at evaluating the diagnostic and outcome prediction
      value of transthoracic impedance cardiography (ICG) in heart failure (HF)
      patients admitted for in-hospital treatment due to flare-ups of their condition.
      MATERIAL AND METHODS In total, 120 patients of intensive care units who were
      admitted due to HF flare-ups were involved to the study. The findings of ICG were
      compared to data obtained by other methods used for diagnosing HF. RESULTS
      Statistically significant (p<0.001) results were obtained when evaluating
      differences in ICG data between admission and discharge from the intensive care
      unit. In addition, a correlation was detected between brain natriuretic peptide
      (BNP) and thoracic fluid content index (r=0.4, p<0.001). Differences in ICG
      values, and BNP data emerged after the participants were grouped according to
      NYHA classes (p<0.05). The evaluation of lethal outcome during 6 months after the
      discharge yielded statistically significant results: BNP >=350 pg/mL (Odds Ratio
      (OR) 4.4), thoracic fluid content >=34 1/kOhm (OR 4.3), and systolic time ratio
      >=0.55 (OR 2.9), p<0.05. CONCLUSIONS ICG data might be applied for the diagnosis
      and prognosis of HF, although the links between ICG and HF need further
      evaluation.

PMID- 30227446
TI  - A Systematic Review of Prenatally Diagnosed Intra-abdominal Enteric Duplication
      Cysts.
AB  - INTRODUCTION:  With improvements in prenatal ultrasound, more abdominal enteric
      duplication cysts (EDCs) are diagnosed prenatally. The optimal time for operative
      intervention is unclear. We aimed to review the evidence supporting the
      indication and timing of surgery for prenatally diagnosed EDCs. MATERIALS AND
      METHODS:  A systematic review was performed using a defined search strategy
      identifying articles with inclusion criteria of prenatal diagnosis of
      histologically confirmed EDCs. Outcomes included (1) indications for resection
      (symptoms vs. prophylactic) and (2) time from birth to operative intervention.
      RESULTS:  Of 1,590 articles screened, prenatal diagnosis of histologically
      confirmed EDCs was made in 68 articles, detailing indications and timing for
      resection for 86 patients. Thirty-five patients (41%) became symptomatic early
      and were resected promptly at a median of 2 days of age. Indications for
      intervention included bowel obstruction, volvulus, bleeding, recurrent pain and
      diagnostic dilemma (concern for cystic neuroblastoma). There were 51 patients
      (59%) who were resected prophylactically at a median of 90 days of age without
      interval symptoms. Symptomatic cysts had a larger mean cyst diameter. There was a
      difference in the anatomic distribution of asymptomatic or symptomatic EDCs
      gastric duplications were more frequently asymptomatic while jejunal, proximal
      ileal and colonic duplications were more frequently symptomatic. CONCLUSION:  The
      optimal approach to EDCs diagnosed prenatally is not supported by strong evidence
      in the literature. Our systematic review indicates that almost half of the
      infants diagnosed prenatally become symptomatic early and are resected. In
      asymptomatic patients, close observation and delayed prophylactic resection in
      infancy can be considered.

PMID- 30227445
TI  - [Role of p16(INK4A) in detection of human papillomavirus DNA and stratification
      of cancer-specific mortality on the basis of long term follow-up data of 34
      patients with invasive penile cancer].
AB  - BACKGROUND:  Human papillomavirus (HPV) infection plays an important role in the
      pathogenesis of penile squamous cell carcinoma (PSCC) in about one third of the
      affected patients. Initial data indicate that HPV status could facilitate
      optimised risk stratification and individualised targeted therapy. The polymerase
      chain reaction (PCR) assay is the reference method for detection of HPV DNA. It
      is unclear if alternatives such as in situ hybridisation (ISH) or various
      surrogate markers (defined as immunohistochemical detection of p16INK4a,
      histological subtype, tumour invasion front, koilocytosis) are sufficient to
      determine HPV status METHODS:  In this single centre study on 34 patients with
      PSCC, multiplex nested PCR and ISH were conducted for HPV detection and
      identification of HPV DNA genotypes. Various histological criteria and p16INK4a
      were determined by central review. The influence of different criteria on cancer
      specific mortality (CSM) was investigated with the Cox proportional hazards
      models (FU: 92 mo.). Furthermore, the discriminative qualities of various tumour
      invasion patterns (i. e., pT-classification 7th vs. 8th ed.) for CSM prediction
      were compared. RESULTS:  Pursuant to PCR assay, HPV DNA was detected in 26 % of
      patients (n = 9). ISH and the examined histological criteria were of inadequate
      quality in the prediction of HPV status (p > ;0.3). Test parameters of p16INK4a
      were calculated as follows: sensitivity 66.7 %, specificity 84 %, positive
      predictive value 60 %, negative predictive value 87.5 %, overall agreement 79.4 %
      (Area-Under-Curve: 0.753, p = 0.026). None of the examined HPV criteria
      significantly influenced CSM. In comparison to the 7th pT-edition, the 8th
      version was superior in CSM prediction (c-indices 70.2 % vs. 72.9 %). In addition
      to penile corpora invasion, infiltration of the urethra had no independent
      predictive value. Regrouping of the corpora invasion patterns, as proposed by us,
      resulted in an increase in discriminative quality (c-index 77.9 %). CONCLUSIONS: 
      In contrast to ISH and the examined histological criteria, p16INK4a allows a
      reasonable prediction of HPV status. Neither HPV DNA nor its surrogate markers
      independently impacted CSM. As urethral tumour invasion does not independently
      influence CSM, the recent pT classification can be considered useful for
      prognosis.

PMID- 30227448
TI  - Intravenous Corticosteroids to Improve Early Rehabilitation in Total Knee
      Arthroplasty.

PMID- 30227447
TI  - Minor and Major Complications Related to Minimally Invasive Repair of Pectus
      Excavatum.
AB  - The technique for minimally invasive repair of pectus excavatum (MIRPE) has been
      adopted by most surgeons as the preferred method for treatment of this condition.
      However, there is limited awareness about the complications related to the
      procedure. Most importantly, the prevalence and potential for life-threatening
      complications have frequently been underestimated. The purpose of this
      communication is to increase awareness of the risk of minor and major (life
      threatening) complications, as well as the operative steps and modifications
      which have been developed to prevent them. One of the most common complications
      reported in the early series of MIRPE cases was bar displacement, frequently
      requiring reoperation. Fortunately, technical modifications to the technique have
      resulted in a decrease in the incidence of such events from 10 to less than 2%.
      It is important for surgeons to have a good understanding of the potential
      complications, particularly the major type of complications post-MIRPE and
      postpectus bar removal. Although rare, the risk of mortality is real and it is
      the surgeon's responsibility to ensure optimal patient safety when performing
      this procedure. Factors such as operative technique, patient age, pectus severity
      and asymmetry, previous chest surgery, and the surgeon's experience play a role
      in the overall incidence of adverse events. These preventable events can be
      avoided with proper training, mentoring, and careful patient selection.

PMID- 30227449
TI  - Outcome after Combined Lateral Extra-articular Tenodesis and Anterior Cruciate
      Ligament Revision in Professional Soccer Players.
AB  - We report the functional outcome after combined anterior cruciate ligament (ACL)
      reconstruction and lateral extra-articular tenodesis (LET) for ACL re-rupture and
      high-grade pivot shift in professional soccer players. For this retrospective
      review, the medical records of 24 professional soccer players were analyzed. The
      mean age at surgery was 23.8 +/- 4.2 years and the mean follow-up was 42.2 +/-
      16.9 months. Pre- and postoperative assessment included the KT-1000 Lachman test,
      pivot shift test, International Knee Documentation Committee (IKDC) subjective
      knee evaluation, Tegner activity scale (TAS), and Lysholm score. The rate of
      return to sports and the level of play at final follow-up were recorded. ACL
      revision was performed with an autologous bone-patellar tendon-bone autograft or
      a hamstring graft. LET was performed using an extra-articular MacIntosh procedure
      as modified by Arnold-Coker. Anterior-posterior laxity was significantly reduced
      at the final clinical assessment (p < 0.0001): 22 patients (91.7%) had a negative
      pivot shift and 2 (8.3%) had residual glide (+), with significant improvement (p
      < 0.0001). The mean subjective IKDC and Lysholm score improved from 69.5 +/- 11.1
      (range: 56-90) to 88.4 +/- 8.9 (range: 62.1-100) and from 58.1 +/- 11.7 (range:
      33-72) to 97.4 +/- 3.2 (range: 88-100), respectively, with significant
      improvement (p < 0.0001) over preoperative values. The overall failure rate was
      8.3%. There were no differences between mean preinjury and final TAS scores (p >
      0.05). The rate of return to sports at the same level was 91.7% and the mean time
      to return to sports was 9.2 +/- 2.2 months. Mid-term functional outcome after
      combined extra-articular reconstruction and ACL revision surgery was
      satisfactory, with a reduction in residual postoperative rotatory instability and
      degree of pivot shift.

PMID- 30227450
TI  - Is Arthrodesis a Reliable Salvage Option following Two-Stage Revision for
      Suspected Infection in Proximal Tibial Replacements? A Multi-Institutional Study.
AB  - The aim of this multicentric retrospective study was to verify whether knee
      arthrodesis (KA) is a viable reconstructive option after two-stage revision for
      infection of proximal tibia (PT) endoprosthetic reconstruction (EPR). Sixty
      patients who underwent a two-stage revision were included. Definitive EPR or a KA
      with a modular system was performed following consideration of soft tissue and
      extensor mechanism conditions. Patients were evaluated with Musculoskeletal Tumor
      Society Score and Oxford Knee Score. Implant survival was assessed on the basis
      of recurrence of infection. Five patients did not receive any reconstruction
      after the first stage. In 14 cases, a KA was performed, and in 41, an EPR was
      implanted. At 5 years follow-up, reinfection rate in the KA group was lower (10
      vs. 17.5% in KA and EPR groups, respectively). In reinfected patients, the KA
      group had a reduced rate of amputation when compared with those with EPR (50 vs.
      88%). Functional evaluation did not show any significant differences between the
      two groups. A successful KA using a modular implant can eradicate infection and
      allow preservation of the limb with good function and good pain relief in after
      two-stage revision for an infected PT EPR.

PMID- 30227451
TI  - Comparison of Knee Kinematics and Kinetics during Stair Ascent in Single-Radius
      and Multiradius Total Knee Arthroplasty.
AB  - Traditionally total knee arthroplasty (TKA) design has been based on theories of
      the movement of the healthy knee joint. Currently, there are two competing
      theories on the flexion/extension axis of rotation of the knee with disparate
      radii of rotation, and thus differing movement patterns. The purpose of our study
      was to compare stair ascent kinematics and kinetics of single-radius (SR) and
      multiradius (MR) TKA subjects. We hypothesized that the knee kinematics and
      kinetics of SR TKA patients would more closely replicate healthy age matched
      controls during stair ascent than MR TKA patients, 1 year after TKA. Both patient
      groups had large improvements in biomechanical and clinical outcome measures
      following surgical intervention. However, the SR knee design performs closer to
      healthy controls than MR knees during stair ascent, supporting results that have
      been previously obtained for level walking. SR TKA subjects demonstrated reduced
      power production and sagittal moment compared with controls, albeit more than MR
      TKA subjects. This study demonstrates that patients who receive SR TKA have
      kinematics more closely aligned to normal patterns postoperatively than those who
      received an MR TKA. The power production and sagittal moment of the healthy
      controls most closely match previously published values of younger adults, SR TKA
      group most closely matches older adults, while the MR TKA group has lower power
      production and sagittal moments than either previously published age group. This
      strongly suggests that the biomechanical differences found in this study are
      evidence of functional deficiencies. Further research is needed to determine how
      these deficiencies progress with patient aging.

PMID- 30227452
TI  - Managing Superficial Distal Medial Collateral Ligament Insufficiency in Primary
      Total Knee Arthroplasty Using Bone Staples.
AB  - Superficial medial collateral ligament (MCL) injury is an occasional
      intraoperative complication during total knee arthroplasty (TKA) that can lead to
      failure. Although previous studies have recommended complex repair or conversion
      to a constrained implant, the authors evaluated results of superficial distal MCL
      reapproximation using bone staples. Records of 31 patients who underwent staple
      reapproximation for superficial MCL avulsion from the tibial attachment during
      primary TKA from 2005 to 2015 were reviewed. They were compared with 685 patients
      who underwent uncomplicated TKA (primary control) and 18 who underwent revision
      TKA for instability (secondary control). Subjective knee instability was assessed
      with a patient questionnaire, and other end points included revision for
      instability or stiffness and manipulations under anesthesia. The authors
      prospectively collected Knee injury and Osteoarthritis Outcome Score (KOOS) and
      visual analog scale satisfaction scores. The mean follow-up was 2.6 years. No
      patients treated with staple repair required revision for instability, whereas
      two patients were revised in the primary control. Subjective instability was
      reported in 19.2% of staple repair patients compared with 24.2 and 46.2% of
      patients in the primary and secondary controls. The mean KOOS for the staple
      group was 71.7 points, 77.3 for the primary control, and 49.3 for the secondary.
      KOOSs for the staple group were 5.6 points lower than the primary control, but
      22.4 points higher than the secondary. Staple reapproximation is a simple and
      effective method for repairing the superficial distal MCL in primary TKA. The
      rate of instability and functional outcomes was comparable to uncomplicated
      primary TKA.

PMID- 30227453
TI  - The Extended Purse-String Rhytidectomy.
AB  - Facelifts remain a critical part of a facial plastic surgeon's cosmetic practice.
      Techniques continue to evolve, while at the same time patients demand less
      invasive procedures with less morbidity. The authors present a facelift plication
      technique using wide purse-string sutures placed into the superficial
      musculoaponeurotic system and platysma. This is a retrospective review with a
      level of evidence 3 set at a medical spa and tertiary referral center designed to
      assess a purse-string suture technique using an inner followed by an outer purse
      string, with refinements being made during the timeframe of the review. One
      hundred and eighteen patients were reviewed and 95 were included in the study
      given the inclusion criteria of a minimum of 1-year follow-up. Based on the
      subjective judgment of the primary surgeon, 37 patients were found to have
      excellent results, while 43 patients were judged as having good results. The
      judgment was based on the physical exam improvement of the aging aspects of the
      patient, and patient satisfaction. Ten patients displayed fair results (the
      patients were marginally happy), and five patients were noted to have poor
      results (they were notably unhappy). Complications included eight hematomas, five
      patients with prominent scars, and one patient with skin loss in the temple
      region. There were no cases of facial nerve injury. The extended purse-string
      rhytidectomy is a good alternative to traditional facelift techniques. This
      offers a plication method that results in the vertical vector that is now
      considered of paramount importance with all facelifts. The authors feel that it
      is a valuable tool that can be considered in most patients presenting for aging
      face surgery.

PMID- 30227454
TI  - A 2-Year Follow-up Study of an Absorbable Implant to Treat Nasal Valve Collapse.
AB  - The safety and effectiveness of an absorbable implant for lateral cartilage
      support have been recently demonstrated in subjects with nasal valve collapse
      (NVC) at 12 months postprocedure. This follow-up study aimed to assess whether
      the safety and effectiveness of the implant persist in these patients for 24
      months after the procedure. Thirty subjects with Nasal Obstruction Symptom
      Evaluation (NOSE) score >= 55 and isolated NVC were treated; 14 cases were
      performed in an operating suite under general anesthesia and 16 cases were
      performed in a clinic-based setting under local anesthesia. The implant, a
      polylactic acid copolymer, was placed with a delivery tool within the nasal wall
      to provide lateral cartilage support. Subjects were followed up through 24 months
      postprocedure. Fifty-six implants were placed in 30 subjects. The mean
      preoperative NOSE score was 76.7 +/- 14.8, with a range of 55 to 100. At 24
      months, the mean score was 32.0 +/- 29.3, reflecting an average within-patient
      reduction of -44.0 +/- 31.1 points. There were no device-related adverse events
      in the 12 to 24 months period. There were five subjects who exited the study
      prior to the 24-month follow-up. Four of the five subjects who exited were
      elected for further intervention and one subject was lost to follow-up. This
      study demonstrates safety of an absorbable implant for lateral nasal wall support
      and symptom improvement in some subjects with NVC at 24 months postprocedure.

PMID- 30227455
TI  - SMFM 2018 Archive: Prematurity-Part 4 (Podcast).

PMID- 30227457
TI  - Moderate-intensity Arm-cranking Exercise may not Improve Arterial Function in
      Healthy Adult Men.
AB  - Endurance exercises, such as cycling or running, are useful for improving
      arterial function. However, people suffering from partial paralysis or arthritis
      are unable to perform these kinds of lower-limb exercises. In the present study,
      we explored the acute effect of upper-arm exercise on arterial stiffness in
      healthy men. Fourteen healthy adult men performed two experimental trials. The
      order of experiments was randomized between a 30-min arm-cranking exercise at 50%
      VO2max (A-trial) and a 30-min leg-cycling exercise at 50% VO2max (C-trial). The
      brachial to ankle pulse wave velocity (baPWV), brachial systolic/diastolic blood
      pressure and heart rate were obtained with subjects in the supine position. The
      baseline hemodynamic values were not markedly different between the two trials.
      Compared with the baseline value, the baPWV was significantly reduced at 30 and
      60 min after the C-trial. In the A-trial, however, there were no significant
      changes in the baPWV throughout the trial. These results indicate that acute 50%
      VO2max arm-cranking exercise induced relatively little change in the baPWV, which
      was the opposite of the finding observed with leg-cycling exercise. Therefore, in
      order to improve arterial function via aerobic upper-arm exercises, the exercise
      mode/intensity or other approaches should be considered.

PMID- 30227456
TI  - Does Chronic Ankle Instability Influence Knee Biomechanics of Females during
      Inverted Surface Landings?
AB  - The primary purpose of the study was to determine whether atypical knee
      biomechanics are exhibited during landing on an inverted surface. A seven-camera
      motion analysis system and two force plates were used to collect lower extremity
      biomechanics from two groups of female participants: 21 subjects with chronic
      ankle instability (CAI) and 21 with pair-matched controls. Subjects performed ten
      landings onto inverted and flat platforms on the CAI/matched and non-test limbs,
      respectively. Knee and ankle joint angles, joint angular displacements, joint
      moments and eccentric work were calculated during the landing phase and/or at the
      initial contact. Paired t-tests were used to compare between-group differences
      (p<0.05). We observed that CAI group displayed a significantly increased knee
      flexion angle, knee flexion displacement, peak knee extension moment and internal
      rotation moment, and eccentric work in the sagittal plane, possibly due to
      altered ankle biomechanics. Participants with CAI employed some compensatory
      strategy to improve their ankle and postural stability during landing onto the
      tilted surface. The increased knee extension and internal rotation moments of CAI
      participants could potentially result in a greater ACL loading. In future
      studies, it may be worthwhile to measure or estimate the ACL loading to confirm
      whether CAI could relate to the mechanism of ACL injury.

PMID- 30227459
TI  - Catecholamine-Induced Cardiomyopathy in Pheochromocytoma: How to Manage a Rare
      Complication in a Rare Disease?
AB  - Pheochromocytomas and paragangliomas (PHEOs) are rare neuroendocrine tumors.
      Clinical manifestations include different cardiovascular signs and symptoms,
      which are related to excessive secretion of catecholamines. Catecholamine-induced
      cardiomyopathy in PHEO (CICMPP) is a rare but dreaded complication of PHEO. Once
      patient is diagnosed with this condition, the prognosis is worse and a surgical
      risk is much higher than expected. This article focuses on how catecholamines
      affect the heart and the pathophysiologic mechanism of CICMPP. The cardiovascular
      responses to catecholamine depend mostly on which catecholamine is released as
      well as the amount of catecholamine that is released. The acute release of
      norepinephrine and epinephrine from PHEO increases heart rate, systemic vascular
      resistance, myocardial contractility, and reduces venous compliance. The
      excessive adrenergic stimulation by catecholamine results in severe
      vasoconstriction and coronary vasospasm, myocardial ischemia, and subsequently
      damage, and necrosis. Chronically elevated catecholamine levels lead to
      significant desensitization of cardiac beta-adrenoceptors. The increased levels
      of the enzyme beta-adrenoceptors kinase (betaARK) in the heart seems to mediate
      these biochemical and physiological changes that are consistently correlated with
      attenuated responsiveness to catecholamine stimulation. Through these mechanisms
      different types of cardiomyopathy (CMP) can be formed. This review discusses
      extensively the 3 types of cardiomyopathies that can be present in a PHEO
      patient. It also provides the clinical presentation and diagnostic and
      therapeutic algorithm in managing patients with CICMPP.

PMID- 30227460
TI  - Introduction to the Special Section on Medical Communications: Medical
      Communications Transformation Within the Emerging Health Care Landscape.

PMID- 30227458
TI  - Peak Fat Oxidation is not Independently Related to Ironman Performance in Women.
AB  - The aim of the present study was to investigate if peak fat oxidation rate (PFO)
      is related to Ironman performance in female athletes. Thirty-six female Ironman
      athletes (age: 34+/-1 yrs, [21-45 yrs.] SEM [Range]) with a BMI of 22.1+/-2.0
      kg/m2 [18.8-28.4 kg/m2], a body fat percentage of 24.8+/-1.0% [9.0-37.0%] and a
      VO2peak of 53.0+/-1.3 ml/min/kg [36.5-70.5 ml/min/kg] were tested in the
      laboratory prior to the Ironman Copenhagen 2017. Race time ranged from 9:17:07 to
      15:23:48 with mean race time being 11:57:26 h:min:s (717 min). By simple linear
      regression analyses we found associations between race time and P FO (r2=0.22,
      p<0.005), VO2peak (r2=0.65, p<0.0001) and the relative exercise intensity
      eliciting PFO (Fatmax) (r2=0.35, p=0.0001). Furthermore, associations were found
      between race time and body fat percentage (r2=0.44, p<0.0001) and age (r2=0.16,
      p<0.05). By means of multiple regression analysis, VO2peak was the only
      statistically significant variable explaining 64% of the variation in race time
      (adj. r2=0.64, p<0.005). In conclusion, these results demonstrate that PFO is not
      independently related to Ironman performance in a heterogeneous group of female
      athletes. Interestingly, VO2peak alone was able to predict 64% of the variation
      in Ironman race times.

PMID- 30227461
TI  - Medical Information Services: How Are We Trending?
AB  - As the pharmaceutical and biotechnology industry continues to undergo
      transformative changes with mergers and acquisitions, loss of patent exclusivity,
      increased collaborations, and health care reform, Medical Information departments
      have changed as well. A total of 25 companies were asked to participate in a
      telephone survey to better understand the trends and adaptations over the last 5
      years. Of these, 21 companies participated; the response rate was 84%. The survey
      focused on 5 key areas: operations and demographics, outsourcing, diversity of
      responsibilities, value, and health care reform. Results from this survey
      indicate an increase in outsource activity with expanded contact center functions
      and continued interest in globalization. Changes over the past 5 years were noted
      for promotional review, sales training, medical booth convention coverage, field
      medical slide review, inquiry volume, and support for products approved through
      the 505(b)(2) pathway. The full impact of health care reform remains to be
      determined; however, an increase in consumer inquiries is expected. Results from
      this research should be considered for future surveys.

PMID- 30227462
TI  - Serialization: Benefits Beyond Regulatory Compliance.
AB  - As pharmaceutical and biotech markets continue to globalize, there are increasing
      concerns for ensuring the safety and legitimacy of pharmaceutical products. An
      efficient network in which the supply chain is secure and patients are safe is of
      great importance to the reputation of the industry in today's global marketplace.
      Consequently, systems and processes for identifying products through the supply
      chain are being put into place to meet new regulations. These same systems and
      processes offer the industry an opportunity to move beyond compliance and reap
      additional benefits affecting overall performance and patient adherence.

PMID- 30227463
TI  - Implementing Adjusted Imaging Metrics Within Roche With the Metrics Champion
      Consortium: Experiences and Outcome.
AB  - PURPOSE: To implement adjusted performance imaging metrics on imaging clinical
      trials of a pharmaceutical company (Roche) in a business relationship with
      preferred imaging providers and to report on findings and lessons learned.
      METHODS: In 2009 the Metrics Champion Consortium provided the first imaging
      metrics for use in clinical trials as industry consensus. Roche reviewed,
      adjusted, excluded, and extended these metrics and defined target values per
      metric in order to implement them in all clinical trials with 7 preferred
      providers. RESULTS: Roche preferred providers were able to report on all 19
      metrics (8 unchanged Metrics Champion Consortium, 7 adjusted, and 4 Roche
      defined). Seventy-three Roche studies over 27 months form the basis for
      reporting; data are provided as mean and standard deviation per disease area with
      number of studies and for all studies reported for the specific metric for all
      providers. Disease areas are oncology, central nervous system, and inflammation.
      Seventeen metrics have proven to be useful; 2 metrics did not provide sufficient
      information; and 4 metrics need adjustments of target values. LIMITATIONS:
      Imaging trial-related metrics are a new concept, and Roche and providers had to
      develop the same consistent understanding of content and how to report a specific
      metric. The 73 studies covered all phases and disease areas, which made it
      difficult at times to compare results. CONCLUSIONS: Imaging metrics in clinical
      trials are a useful tool in improving timeliness and quality of imaging data,
      enhancing trial processes, and governing sponsor/provider relationships. It
      increases the transparency in the business relationship and in the different
      clinical trial-related process steps. The use of metrics highlights critical
      topics, such as reading and adjudication, and enables parties to take actions to
      improve performance. Disease area-related reporting needs more data for specific
      improvements.

PMID- 30227464
TI  - Does the Essential Medicines Policy Succeed in China? Empirical Study on Rational
      Medicine Use in Primary Health Care Institutions.
AB  - This study investigated outpatient prescription medicines use in primary health
      care institutions to evaluate the impact of the essential medicines policy on
      rational medicines use. Data were collected from primary health care institutions
      in 4 province-level areas of different socioeconomic status in China. Around the
      policy implementation, the numbers of various medicines used per prescription
      were compared by t test and 1-way analysis of variance, and the proportions of
      prescriptions with antibiotics, injections, or hormones were compared by chi
      square test. After the policy implementation, the numbers of all medicines and
      antibiotics used per prescription dropped, and the number of essential medicines
      used per prescription increased in all 4 areas. The percentage of prescriptions
      with injections declined in all 4 areas, but the percentages of prescriptions
      with antibiotics or hormones witnessed different status in different areas. To a
      certain degree, the essential medicines policy in China has taken effect on
      rational medicines use but needs development.

PMID- 30227465
TI  - Timeliness of a Signal Detection Process as a Component of Effectiveness
      Assessment in a Drug Safety Department of a Large Pharmaceutical Company: Review
      Over a 5-Year Period.
AB  - The effectiveness of a signal detection process integrating traditional and data
      mining techniques was evaluated retrospectively in the real-world setting of a
      drug safety department at a large pharmaceutical company. To this effect, annual
      metrics on all signals detected internally or externally for all approved
      Novartis drugs were reviewed from January 1, 2007, to December 31, 2011.
      Timeliness (ie, the ability of the signal detection process to detect signals
      prior to any regulator) was taken as a main component of effectiveness. Over this
      5-year period, 568 (about 17%) of the 3481 signals submitted by the safety
      management team at the signal escalation boards were identified as new or
      changing signals. Of these 568 signals, 53 (10%) were detected first by health
      authorities (a quarter of which were class signals). In conclusion, the signal
      detection process at Novartis Pharmaceuticals could detect at least 9 of 10
      signals prior to them being detected by health authorities.

PMID- 30227466
TI  - Review of the Evolution of Medical Information in Light of Changes in the
      External Landscape.
AB  - Over the past 25 years, biopharmaceutical companies have faced and adapted to an
      external landscape that has grown increasingly complex and challenging. Medical
      information departments have played a fundamental role in the globalization
      process through their development of multichannel customer-facing resources that
      address the complexities with innovative solutions. The authors conducted a
      survey to determine key components of the globalization of medical information
      departments in large biopharmaceutical companies. In this article, they present
      survey findings and propose key components to the globalization process in
      medical information. Finally, they offer considerations for providing more
      patient-focused responses and processes for evaluating the impact of the medical
      information department in a global framework through the multifaceted measurement
      of customer satisfaction.

PMID- 30227467
TI  - The Impact of the Great East Japan Earthquake on Research Activity in a Disaster
      Stricken Area.

PMID- 30227468
TI  - New Governmental Regulatory System for Stem Cell-Based Therapies in Japan.
AB  - Regenerative medicine using stem cells is expected to provide tools for the
      replacement or repair of damaged tissues, opening up the possibility of treating
      many diseases that cannot otherwise be effectively treated. To promote the
      development of and access to regenerative medicine, it is important to take a
      balance of expedited provision of innovative therapies and appropriate steps to
      ensure safety and efficacy. While most developed countries have various
      regulatory frameworks for clinical trials and medical treatments involving stem
      cells, the Act on the Safety of Regenerative Medicine and the Revised
      Pharmaceutical Affairs Law have recently been simultaneously passed by the
      Japanese Diet. According to the former act, these medical technologies are
      categorized into 3 classes depending on their anticipated potential risk to human
      health, and the specific procedures falling into each class are determined. In
      addition, the act enables medical institutions to commission cell processing by
      business facilities outside the institution (even foreign facilities) that
      fulfill the requirements set out by the Ministry of Health, Labour and Welfare,
      with the aim to promote collaboration between academia and industry from an early
      stage. According to the latter law, a therapeutic product for regenerative
      medicine is defined as a product distinct from pharmaceuticals and medical
      devices, enabling regenerative medical products to be given a conditional, time
      limited marketing authorization much earlier than that under the previous system.
      The new legal framework of regenerative medicine is expected to achieve the aim
      to develop and promote regenerative medicine, aiming at timely provision of safe
      and effective therapies and products.

PMID- 30227469
TI  - Competitive Strategies for Japanese Clinical Trial Sites: A New Approach to
      Quality.
AB  - In Japan and other major East Asian countries in the global drug development
      scene, trial sites play a major role in conducting clinical trials by intervening
      between sponsors and investigators. The recent globalization of clinical
      development has been intensifying competition among the regions, trial sites, and
      investigators in terms of cost, speed, and quality. The quality of clinical
      trials-the key factor for competitiveness-is now being defined with a risk-based
      approach. Within this backdrop, Japanese trial sites now assume a new role in
      attaining the necessary amount of quality with increased efficiency. The author
      proposes strategies for Japanese trial sites to explore the potential to survive
      the competition. These strategies include further differentiation among trial
      sites and building in-house quality systems in hospitals. The strategies should
      be viable in other Asian countries with similar institution-based systems of
      conducting clinical trials.

PMID- 30227470
TI  - Risk Evaluation and Mitigation Strategies With Elements to Assure Safe Use:
      Alignment of the Goals With the Tools to Manage Risk.
AB  - The Food and Drug Administration Amendments Act of 2007 gave the FDA the
      authority to require drug sponsors to submit a risk evaluation and mitigation
      strategies (REMS) program for those medicines with serious risks such that
      failure to effectively manage these risks would tip the benefit-risk balance. As
      of August 8, 2013, the 34 distinct individual and shared REMS programs that have
      specific elements to assure safe use (ETASU) were reviewed to ascertain the types
      of risks managed, the goals of the REMS, and the tools that were employed
      targeting prescribers, health care facilities, pharmacists, and particular
      conditions for safe use. Most REMS (65%) have a combination of risk mitigation
      and educational goals, but 4 REMS programs (12%) have exclusively educational
      goals. Preventing fetotoxicity (25%) is the most common risk managed by REMS with
      ETASU. Seventy-nine percent of ETASU REMS employ prescriber-based tools that
      include performing laboratory testing (eg, pregnancy, hepatic enzymes) or
      monitoring (eg, ophthalmologic examinations, documenting vaccination). The goals
      of REMS programs should focus on measurable behaviors that directly reduce risk.
      The tools that are employed should create the appropriate conditions for safe
      use. With the number of programs and the plethora of tools applied, serious
      consideration should be given to better integration of risk management into
      health care and pharmacy systems that are best equipped to manage such risks.

PMID- 30227471
TI  - Evaluating Source Data Verification as a Quality Control Measure in Clinical
      Trials.
AB  - TransCelerate has developed a risk-based monitoring methodology that transforms
      clinical trial monitoring from a model rooted in source data verification (SDV)
      to a comprehensive approach leveraging cross-functional risk assessment,
      technology, and adaptive on-site, off-site, and central monitoring activities to
      ensure data quality and subject safety. Evidence suggests that monitoring methods
      that concentrate on what is critical for a study and a site may produce better
      outcomes than do conventional SDV-driven models. This article assesses the value
      of SDV in clinical trial monitoring via a literature review, a retrospective
      analysis of data from clinical trials, and an assessment of major and critical
      findings from TransCelerate member company internal audits. The results support
      the hypothesis that generalized SDV has limited value as a quality control
      measure and reinforce the value of other risk-based monitoring activities.

PMID- 30227472
TI  - Evaluation of the Gulf Cooperation Council Centralized Procedure: The Way
      Forward.
AB  - The aim of the study was to evaluate the Gulf Cooperation Council (GCC)
      centralized regulatory review process. Regulatory review times-including
      submission and application dates for new active substances (NASs) and existing
      active substances (EASs) using a standardized template for the period of 2006 to
      2010-were collected directly from the GCC office located in Riyadh, Saudi Arabia.
      A total of 413 products (96 NASs and 317 EASs) were approved during the period,
      with an overall significant increase in the EASs ( P < .001). The median approval
      times increased from 107 calendar days in 2006 to 265 in 2010 ( P < .001). The
      lowest approval time was for EASs submitted by the Gulf companies (134 days) and
      the longest for NASs submitted by international companies (346 days) ( P < .001).
      These data were also analyzed according to therapeutic classes and dosage forms.
      The results also showed that the lowest number (n = 16) approved during the
      period was in 2010, and this was due to a major regulatory change implementing
      the International Conference on Harmonisation product stability guideline for the
      region. The findings indicate that the delay and the wide range in approval times
      could be reduced by utilizing a standard assessment template for product review
      and the implementation of a clock stop system for company responses to questions
      from the GCC central registration committee. Furthermore, using information
      technology tools would speed up the registration process rather than the manual
      exchange of product registration files between the executive office and the
      member states.

PMID- 30227473
TI  - Insights Into the Decision Making of Advisory Groups to the Italian Medicines
      Agency.
AB  - The Italian Medicines Agency (AIFA) is enhancing a strong transparency-oriented
      policy to improve information exchange and decision making with stakeholders. To
      this end, a questionnaire titled "Survey AIFA 2013" was sent to the 72 selected
      contacts on February 17, 2013 (closing date April 3, 2013), to assess influence
      on committees and secretariats' opinions and decisions. The survey was divided
      into 2 sections (17 questions) with a 10-minute time limit. The results show that
      external resolutions have little influence on internal advisory groups, whereas
      internal ones carry more weight. So-called intellectual bias needs careful
      monitoring, as it can potentially condition decisions.

PMID- 30227474
TI  - The Life Cycle and Management of Protocol Deviations.
AB  - Clinical trials are designed to evaluate the efficacy, safety, or other
      characteristics associated with medical products. Trials are usually complex and
      require a large group of professionals to follow a clinical trial protocol,
      standard operating procedures, and study-specific manuals, guidelines, and plans.
      Clinical trial protocols prospectively describe the background and rationale for
      conducting the trial, the objectives of the trial, the trial design, the
      equipment to be used, the procedures to be performed, and the statistical methods
      on how the trial data are to be analyzed. Deviations from the protocol can result
      in harm to subjects, biased or inaccurate results, and possible rejection of all
      or part of the trial data by the sponsor or regulatory authorities. Despite
      preventive efforts, protocol deviations are likely to occur in most trials. This
      position paper proposes a common definition of protocol deviations and recommends
      best practices for their detection, classification, and management as part of
      their life cycle, with a goal of reducing their impact on subject safety and data
      integrity. The information contained herein is drawn globally from industry
      experts within the DIA Good Clinical Practice and Quality Assurance community, an
      industry-wide survey, and presentations with discussions at various industry
      meetings.

PMID- 30227475
TI  - Whence a Journal....

PMID- 30227477
TI  - Industry Practices for Expedited Reporting to Investigators Conducting Research
      Under an IND.
AB  - Due to investigators' complaints about the volume and limited interpretability of
      expedited safety reports received in Investigational New Drug (IND) studies, the
      authors surveyed industry sponsors in late 2009 about their reporting practices.
      An Internet-enabled survey was submitted to 51 industry sponsors. Ten (20%)
      complete surveys were returned, 9 of which came from large
      pharmaceutical/biotechnology companies. Although the response rate in this study
      was low, considering the consolidation present in this sector, the preponderance
      of responses from large pharmaceutical companies provides a useful description of
      the safety reporting practices of a significant sector within the medical
      products industry. Sponsors described extensive safety-specialized resources for
      reporting individual events to the FDA and IND investigators. Aggregate reports,
      when prepared, were provided to the FDA but rarely to investigators. Sponsors
      reported receiving complaints from investigators about excessive volume and
      limited relevance of individual safety reports. These data suggest that
      investigators would likely benefit if industry sponsors decreased reporting of
      individual cases that are not readily interpretable and instead reported
      meaningful safety information from aggregate analyses.

PMID- 30227476
TI  - Current Practice in Japan for the Prevention and Treatment of Missing Data in
      Confirmatory Clinical Trials: A Survey of Japanese and Foreign Pharmaceutical
      Manufacturers.
AB  - This study aims to survey the current practice in Japan for the prevention and
      treatment of missing data in clinical trials since the publication of regulatory
      guidelines on missing data issues. A web-based questionnaire was conducted among
      65 member companies of the Japan Pharmaceutical Manufacturers Association in
      2013. Responses were obtained on 187 clinical trials from 55 companies, including
      42 based in Japan and 13 based in other countries. Missing data were most
      frequent in trials involving the central nervous system (65.2% had >=10% missing
      data). Overall, last observation carried forward (LOCF) was the most popular
      method for handling missing data (45.0%), followed by mixed-effect models for
      repeated measures (15.5%), although this was used as frequently as LOCF
      imputation in central nervous system trials. Even after the publication of
      regulatory guidelines discouraging use of LOCF, LOCF imputation remains the most
      popular method for treating missing data among pharmaceutical manufacturers in
      Japan.

PMID- 30227478
TI  - Regulatory Reforms in India.
AB  - While India is a favorable destination for conducting clinical trials, recent
      reports of alleged deaths due to serious adverse events and inadequate
      compensation have led regulators in India to take measures and initiatives. Some
      examples include introducing guidance documents, advisory committees, a
      compensation clause in informed consent forms, clinical trial registries,
      registration of contract research organizations and ethics committees,
      pharmacovigilance programs, notices for periodic safety update report submission,
      notices to ethics committees, and inspections for streamlining the regulations.
      These steps will further ensure the accountability of the stakeholders involved
      while India continues to conduct trials.

PMID- 30227479
TI  - Strategies for a Label Claim or Indication in the Context of Robust Point
      Estimates From Historical Data.
AB  - For label claims or indications, especially in the US, prospectively designed
      clinical trials are usually required. However, when robust data are available and
      indicate a nearly unmistakable performance of the product of interest, the post
      hoc analysis should be seriously considered for the label claim or indication
      purpose. In this article, post hoc, Bayesian, and stand-alone new trial analyses
      are discussed and compared so that under such situations, a decision-making
      process could be facilitated.

PMID- 30227480
TI  - The Roles of Regulatory Science Research in Drug Development at the
      Pharmaceuticals and Medical Devices Agency of Japan.
AB  - Recently, it is becoming increasingly difficult to develop innovative drugs.
      Thus, the role of regulatory science research in drug development and
      postmarketing settings has become more important. In this article, the authors
      discuss the roles of regulatory science research at the Pharmaceuticals and
      Medical Devices Agency (PMDA), which aims to improve public health in Japan.

PMID- 30227481
TI  - Influence of Clinical Research Investigator Fraud on Clinical Trial
      Participation.
AB  - The number of clinical research investigators that the US Food and Drug
      Administration has disqualified or totally restricted has been increasing since
      1964. In addition, several public polls and surveys indicate a major dilemma in
      clinical trial participation and public perceptions of clinical research. This
      study investigates how clinical investigator fraud or misconduct influences
      public perceptions of participation in clinical trials. An electronic survey was
      developed for the faculty of Eastern Michigan University. The survey results
      (11.2% response rate) indicated that 81% of respondents were willing to consider
      participation in a clinical trial or had participated. However, when the
      respondents were told of a case of investigator fraud, approximately 25% of
      willing respondents were now discouraged from participation. The influence of the
      knowledge of investigator fraud did not seem to be greatly correlated with the
      geographic location of the event relative to the location of the respondents.
      While it seems that news of investigator fraud would therefore significantly
      affect enrollment efforts in ongoing clinical studies, these results reflect only
      a select group of highly educated people, and more definitive studies are
      recommended to understand the impact of investigator fraud and the duration of
      this impact on patient recruitment into clinical studies.

PMID- 30227482
TI  - Exploring Best Practices on Development Regulatory Affairs and Clinical
      Development Related to Multiregional Clinical Trials (MRCTs) in China, Korea, and
      Taiwan.
AB  - Editor's Note: In this Meeting Report, Tetsuomi Takano provides an excellent
      summary of 2 related tutorial sessions held at the DIA 6th Annual Conference in
      Japan for Asian New Drug Development (KFC Hall, Tokyo, Japan, April 27, 2012).
      The sessions focused on best practices for development regulatory affairs and
      clinical development related to multiregional clinical trials (MRCTs) in China,
      Korea and Taiwan. I am grateful to Mr Takano for this contribution to the
      journal, and I am sure readers will find it both interesting and educational. J.
      Rick Turner, Outgoing Editor-in-Chief  .

PMID- 30227483
TI  - How Korean and White Americans Evaluate and Use Online Advertising and Non
      advertising Sources for Prescription Drug Information.
AB  - This study examined Korean Americans' evaluation and use of online advertising
      and non-advertising sources of prescription drug information and compared the
      findings to those of white Americans. A mail survey was conducted with a
      disproportionate stratified sample of 600 adults (300 general population and 300
      Korean Americans) who have ever taken or are currently taking prescription drugs
      regularly and reside in a metropolitan area in the Midwestern United States.
      While both Korean and white Americans evaluated online non-advertising sources
      more positively than advertising sources, the 2 groups were similar in their
      evaluation of both online advertising and non-advertising sources. White
      Americans tended to use more online advertising sources than did Korean
      Americans, but both groups were equally likely to use non-advertising sources.
      Evaluation and use of online advertising and non-advertising sources by Korean
      and white Americans were associated with different predictors.

PMID- 30227484
TI  - Collaboration and Convergence: Bringing New Medicines to Global Markets in the
      21st Century.
AB  - In the coming years, the drug development process is likely to change
      dramatically as manufacturers, regulators, and payers across the world face
      intense pressure to meet the growing needs of their constituents. Higher hurdles
      in the regulatory and pricing/reimbursement landscape will likely present new
      challenges to the drug development and market access process, which will in turn
      impact patient care. Manufacturers of medicines must focus on "intelligent
      innovation" in which investments are targeted to pursue true therapeutic
      breakthroughs, to minimize the risk of failure, and to maximize global market
      access and patient benefit. The future of the medicines landscape must evolve
      toward a more collaborative framework, where regulatory agencies will pursue a
      greater degree of convergence and where sponsors, regulators, and payers, as
      essential stakeholders, will undertake drug development with reimbursement in
      mind to achieve the common global goal of bringing safe, effective, and
      affordable medicines to the world's people.

PMID- 30227485
TI  - Corporate Integrity Agreements: What They Say About Publications, Publication
      Planning, Transparency, and ICMJE.
AB  - Corporate integrity agreements (CIAs) have become a significant means of
      compliance enforcement for the Office of the Inspector General (OIG) of the US
      Department of Health and Human Services. The objective of this review is to
      present in a factual manner common clauses from recent CIAs that affect
      publications, publication planning, and transparency. Fourteen CIAs issued to
      biopharmaceutical companies from January 1, 2009, through July 31, 2012, were
      reviewed. All documents were publicly accessible on the OIG website. Eight CIAs
      included similar verbiage relating to industry-sponsored publication activities
      and transparency. Each included specific recommendations for author agreements,
      publication plans, needs assessments, publication monitoring, posting of study
      results, and disclosure of relationships with authors. The publishing behaviors
      OIG seeks to effect are consistent with currently accepted guidelines described
      in the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, as
      prepared by the International Committee of Medical Journal Editors (ICMJE) and
      Good Publication Practices for Communicating Company-sponsored Medical Research
      (GPP2), as well as added training, monitoring, and reporting requirements. By
      making clear the importance of publication planning, needs assessments, adherence
      to ICMJE, and reporting of physician payments, and by becoming readily accessible
      to everyone, CIAs provide the industry not only with clear direction for, but
      also an expectation of, responsible behavior when it comes to sponsored medical
      publications.

PMID- 30227486
TI  - Data Quality Improvement in Clinical Databases Using Statistical Quality Control:
      Review and Case Study.
AB  - Ensuring the quality of data being collected in clinical and medical contexts is
      a concern for data managers and users. Quality assurance frameworks, systematic
      audits, and correction procedures have been proposed to enhance the accuracy and
      completeness of databases. Following an overview of the undertaken approaches,
      particularly statistical methods, the authors promote acceptance sampling plans
      (ASPs) and statistical process control (SPC) tools, including control charts and
      root cause analysis, as the technical core of the data quality improvement
      mechanism. They review ASP and SPC techniques and discuss their implementation in
      data quality evaluation and improvement. Two case studies are presented in which
      the authors apply some of the techniques to databases maintained by a local
      hospital. Finally, guidelines are proposed for which techniques are appropriate
      with regard to dataflow and database specifications.

PMID- 30227487
TI  - Relationship Between Progression-Free Survival and Overall Survival Benefit: A
      Simulation Study.
AB  - : This study evaluated the circumstances under which the observed progression
      free survival (PFS) benefit may translate into an overall survival (OS) benefit.
      METHODS: A simulation study, based on PFS and OS joint model decomposition, was
      conducted to evaluate the impact of crossover rates, survival post progression
      (SPP) lengths, and magnitudes of difference in median PFS on OS. Under different
      simulation scenarios, the degree of impact was investigated based on the
      probability of observing a significant OS benefit given an observed PFS benefit.
      RESULTS: Using simulation parameters defined based on historical NDA datasets,
      the probability of detecting an OS benefit given the observed PFS benefit depends
      largely on crossover rate and SPP length (ie, SPP median times). Compared to no
      crossover, a crossover rate of <= 50% decreases the probability of detecting an
      OS benefit by at most 15% regardless of the SPP length. A crossover rate of > 50%
      decreases the probability of detecting an OS benefit much further, and the extent
      of decrease is proportional to the length of SPP. CONCLUSION: Crossover rate and
      SPP length are important factors affecting the benefit translating from PFS to
      OS. This simulation study identified a threshold, of 50%, for crossover rate that
      is likely to confound OS effect. With a greater than 50% crossover rate, longer
      SPP further decreases the probability of translating a PFS benefit to OS.

PMID- 30227488
TI  - Consumers Better Understand and Prefer Simplified Written Drug Information: An
      Evaluation of 2 Novel Formats Versus the Current CMI.
AB  - Patients in the United States receive multiple forms of written drug information
      with their prescription medicines. This study solicited consumers' preferences
      about formatting of information, their motivation to read drug information, and
      their ability to navigate and understand the information. A 3 * 3 study design
      was used in which 3 prototypes for 3 prescription drugs, ORTHO TRI-CYCLENTM
      (norgestimate/ethinyl estradiol), COUMADINTM (warfarin sodium), and PARNATETM
      (tranylcypromine sulfate), were evaluated. The prototypes included 2 novel
      formats ("new" and "bubble") and the "current" format that patients now commonly
      receive with their prescriptions. A total of 105 consumers participated in the
      study. Consumers correctly answered more questions about the medicine when
      presented with a new (70%-95%) or a bubble prototype (83%-92%) than with the
      current format (53%-74%). All attributes scored higher with both prototypes
      compared with the current format. However, in terms of overall preference,
      consumers favored the new prototype and indicated that they would be more
      motivated to read it. Consumers also reported that simple icons assisted them in
      finding important information. The new and bubble prototypes were favored by
      participants more than the current format. Key attributes preferred by consumers
      must be considered as new formats for patient medication information are
      developed.

PMID- 30227489
TI  - Analysis of the Current Situation of Antibiotics Use in China: A Hospital-Based
      Perspective.
AB  - OBJECTIVE: To investigate the present situation of antibiotics use in selected
      hospitals in China according to 2 indicators: hospital-based market sales and
      frequency of usage; based on this information, to assess the government's
      containment policies toward antibiotics overuse. METHODS: Marketing and clinical
      usage data of antibiotics in 420 selected hospitals from 21 major cities and 1
      district in China during 2008-2011 were collected and analyzed. Usage frequency
      was measured by the defined daily dose (DDD) analytic approaches recommended by
      World Health Organization (WHO), and the growth rate of DDDs per patient was
      compared for 3 categories of antibiotics: nonlimited (first line), limited
      (second line), and specially controlled (third line). RESULTS: During the period
      studied, an obvious slowdown was observed in both sales value and the growth of
      sales volume for the 3 categories. With respect to frequency, both limited-level
      and specially controlled level antibiotics with high cost and low safety and
      effectiveness showed an evident decline in the growth rate of DDDs per patient (
      P < .05). However, no significant decline was found for nonlimited antibiotics (
      P > .05). CONCLUSION: The Chinese government's containment policies toward
      antibiotics overuse are beginning to take effect, and antibiotics usage has
      become more measured in major cities. However, China still has a long way to go
      before it can win the battle against antibiotics overuse and drug resistance.

PMID- 30227490
TI  - How FDA Advisory Committee Members Prepare and What Influences Them.
AB  - Since 1992 many changes have occurred in the regulations, guidelines, and
      processes governing the FDA, the biomedical industry, other stakeholders, and
      their interactions. Of particular importance, the FDA Amendments Act of 2007 made
      public advisory committee meetings mandatory for new molecular entities and
      devices requiring clinical trials, unless the necessity of convening such a
      meeting has been waived by the FDA commissioner. For effective preparation,
      product teams must now assume that such a public review will be necessary, even
      if not initially specified by the FDA's review team. To understand what advisory
      committee members actually want from sponsors to enable their informed
      participation, the authors surveyed 101 current or former members of one of the
      FDA's public biomedical advisory committees within the Center for Biologics
      Evaluation and Research, the Center for Drug Evaluation and Research, and the
      Center for Devices and Radiological Health. Their goal was to understand more
      fully their preparatory practices and preferences regarding materials provided by
      the sponsor and the FDA, advisory committee presentations, and Q&A sessions. The
      findings suggest that sponsors need to be clear, concise, and scientifically
      credible, and that some advisory committee members need to be more uniformly
      prepared.

PMID- 30227491
TI  - Editor-in-Chief's Commentary: Therapeutic Innovation & Regulatory Science,
      January 2013.

PMID- 30227492
TI  - Formulating an Ethics Agenda for Drug Development, Regulation, and Utilization.
AB  - An Invitation: The time has come to examine the ethical dimensions of our
      pharmaceutical and device enterprise more broadly. In this inaugural edition of
      Therapeutic Innovation & Regulatory Science (TIRS), Lipworth et al have provided
      a useful introduction to ethical analysis, a framework to guide ethical
      discussions, and a possible research agenda around the ethical aspects of drug
      and device development and policy. It may seem strange to be proposing that TIRS
      become the vehicle for the discussion of the ethical dimensions of policies on
      drug, device, and companion diagnostics development. But for too long our
      "industry" has neglected this dimension of our work, to the detriment of all
      stakeholders, most notably the patient/consumer. All of us are aware that our
      standing as an industry has suffered, and most of us would dearly love to be
      recognized as part of a vital enterprise dedicated to improving human health, not
      only unsullied by scandals fuelling the perception of overriding self-interest
      but also free to explore new ways to contribute to society. We are excited that
      TIRS might become the forum in which new thinking will emerge through systematic
      ethical analyses of pharmaceutical and device policy and practice. As Acting
      Executive Editor and Editorial Board members we hope that you, as a regulator,
      pre-clinical scientist, project manager, patient, clinician, health economist, or
      other stakeholder, will accept this invitation to become involved, and contribute
      to a stimulating and productive discussion about aspects of drug and device
      development that have been relatively overlooked heretofore. Richard Day, Adil
      Shamoo, Wendy Lipworth.

PMID- 30227493
TI  - FDA Engages Collaborators to Address Nonclinical Data Challenges.
AB  - FDA and PhUSE cohosted a Computational Science Symposium (CSS) in 2012 that
      brought stakeholders from the pharmaceutical industry and government to work
      collaboratively to solve common needs and challenges. A nonclinical informatics
      workgroup was formed, dedicated to improving nonclinical assessments and
      regulatory science by identifying, collecting, and prioritizing key needs and
      challenges in the field and then establishing an innovative framework for
      addressing them in a collaborative manner. This paper discusses the process and
      outcomes of the nonclinical informatics workgroup during the CSS and describes an
      approach which crossed organizational barriers to optimize computational science
      for nonclinical assessment.

PMID- 30227494
TI  - Benchmarking the Study Initiation Process.
AB  - The study start-up phase of a trial is an area that pharmaceutical and
      biotechnology companies are focusing on in order to reduce delays and improve
      efficiency. To better understand and examine metrics within study start-up, the
      Tufts Center for the Study of Drug Development, in collaboration with 11
      pharmaceutical and biotechnology companies, examined a comprehensive set of
      metrics and analyzed study data from 105 global clinical trials. The results
      indicate that the early stages of the site initiation process are areas that
      accounted for the majority of cycle time. An examination of cycle time to the
      first patient in by therapeutic area also reveals variation. Variations in cycle
      time to the first patient occur by site type as well as by region. Academic
      institutions and government-funded sites were longest to the first patient in,
      while physician practices were fastest.

PMID- 30227495
TI  - Multi-domain Longitudinal Modeling: An Application to the International Index of
      Erectile Function.
AB  - Individual domains of multi-domain, patient-reported outcome instruments are
      typically analyzed independently, without considering inherent interdependency.
      The authors assessed correlations across time (longitudinal) and across domains
      of a multi-domain instrument, simultaneously, in a single, unified, and cohesive
      integrated model. International Index of Erectile Function (IIEF) data from a
      trial of sildenafil in erectile dysfunction were used. For the multi-domain
      longitudinal modeling, covariance of response was constructed using (1) the
      Kronecker product of an unstructured covariance matrix to model across domains,
      with an unstructured covariance matrix to model across time, and (2) a completely
      general, unstructured covariance matrix. Treatment effects for all IIEF domain
      scores calculated using individual or multi-domain modeling were similar,
      reflecting the robust application of the integrated model to these data. In
      conclusion, modeling correlations simultaneously across domains and across time
      more rigorously address the natural interrelationship between domains and can
      provide a more accurate representation of treatment effects.

PMID- 30227496
TI  - Continuity Correction for the Laster-Johnson-Kotler Noninferiority Asymptotic
      Statistical Test for 2 Independent Proportions.
AB  - Noninferiority asymptotic statistical tests are frequently used in clinical
      trials. The "at least as good as" criterion was introduced by Laster et al in
      2006 for dichotomous data. In this approach (Laster-Johnson-Kotler [LJK]), the
      margin of noninferiority is taken as a percentage of the control response rather
      than a fixed difference. The procedure is seen to be more efficient than the
      fixed margin approach, yielding smaller sample sizes. Also, the procedure offers
      several advantages in the design, statistical efficiency, and interpretability of
      noninferiority trials. However, the LJK procedure has a disadvantage in that its
      size is much greater than the required nominal significance level (alpha). In
      this paper, by using a continuity correction factor, we have adjusted this
      procedure to solve this drawback.

PMID- 30227497
TI  - Treatment and Outcomes of Community-Acquired Pneumonia in Hospitalized Patients:
      The Case of Jimma University Specialized Hospital.
AB  - PURPOSE: This study was conducted with the aim of assessing the treatment
      outcomes of patients admitted to medical wards at a university hospital in
      Ethiopia with a diagnosis of community-acquired pneumonia from March 1, 2008 to
      February 28, 2009. METHODS: A retrospective cross-sectional study was conducted
      from May 14 to 19, 2009. Hospital charts of 104 patients admitted to medical
      wards at Jimma University Specialized Hospital, Jimma, Ethiopia, with a diagnosis
      of community-acquired pneumonia were reviewed. RESULTS: The male-to-female ratio
      was 2.5 to 1, the mean duration of hospital stay was 11.49 days, and crystalline
      penicillin alone was used in 67.3% of cases. Ceftriaxone was the most common
      second-line antibiotic. There were 26.7% of patients who were treated according
      to Ethiopian national treatment guidelines. The overall mortality rate was 20.2%.
      Patient age older than 65 years, respiratory rate greater than 30 breaths per
      minute, and comorbid tuberculosis were associated with poor treatment outcomes.
      CONCLUSIONS: A high death ratio was observed in the present study. Proper
      adherence to standard treatment guidelines and better care for risk groups are
      recommended.

PMID- 30227498
TI  - Optimizing Expedited Safety Reporting for Drugs and Biologics Subject to an
      Investigational New Drug Application.
AB  - In September 2010, the US Food and Drug Administration (FDA) published a final
      rule governing the requirements for expedited safety reporting for products
      subject to an investigational new drug application. The rule clarified the types
      of safety information that qualify for expedited reporting. Its intent was to
      improve the overall quality of safety reporting by reducing the number of
      uninterpretable individual reports sent to the FDA and clinical investigators. In
      December 2011, we surveyed pharmaceutical and biotechnology sponsors regarding
      their safety reporting practices. We convened a group of experts and a
      biostatistics work group to review the survey results and identify gaps between
      current practice and the final safety reporting rule. Most sponsors had not
      changed their approach to expedited reporting of serious adverse events. We
      devised recommendations to help sponsors optimize their premarket safety systems
      to reduce the number of uninformative expedited reports and ensure recognition of
      important safety issues for an investigational drug as early as possible in
      development.

PMID- 30227499
TI  - A Proposed Framework to Address Needs of Clinical Data for Informed Medication
      Use in Pregnancy.
AB  - The objective of this paper is to communicate a proposed framework for addressing
      research limitations and communication barriers that contribute to a lack of data
      for making clinical treatment decisions about medication use in pregnancy. To
      address this global public health concern, a cross-stakeholder coalition composed
      of several workstreams is proposed. The intent is to foster collaborative
      discussion regarding potential solutions to address gaps in communication,
      engagement, and data generation and collection. Topic areas that require focus
      include development of awareness initiatives, cultural transformation efforts,
      collaboration initiatives, research standards, data compilation projects, and new
      data capture methods. Objectives to aid these efforts are outlined, and
      collaboration among researchers, regulators, health care providers, and patients
      is emphasized.

PMID- 30227500
TI  - A Data-Driven Approach to Risk-Based Source Data Verification.
AB  - Source data verification (SDV) is the process of confirming that reliable,
      accurate information collected from participants during a clinical trial has been
      reported successfully to the trial's sponsor by investigators conducting the
      study. Over the past 15 years or so, there has been considerable discussion in
      the literature of alternate (reduced and risk-based) approaches to the
      traditional 100% SDV approach, but these discussions have been theoretical rather
      than data driven. This research therefore employed data from studies conducted by
      the authors' company to answer the following research question: Can historical
      data and simulation methodology be employed to understand the risks (unidentified
      problems) and benefits (cost reductions) of specific reduced SDV scenarios? The
      methodological approach was based upon a 2010 paper published in the Drug
      Information Journal that proposed 4 hypothetical risk-based monitoring
      approaches. The paper's authors proposed well-thought-out and defined scenarios
      that were readily replicated in simulation algorithms. These scenarios therefore
      facilitated the exploration of whether real data could be used to simulate
      reduced SDV scenarios. These data came from 30 trials that had utilized
      electronic data capture and were completed between 2005 and 2010. Findings
      revealed that real study data can successfully be used to simulate reduced SDV
      scenarios, bringing a data-driven analytical approach to the determination of
      efficient and effective approaches to reduced SDV, hence translating our
      theoretical understanding to data-driven methodology.

PMID- 30227501
TI  - Cross-regional Pharmaceutical Technology Transfer in China: Patterns and Proposed
      Investment Strategies.
AB  - The Chinese pharmaceutical market is undergoing dramatic growth, with a huge
      population, urbanization, a growing number of elderly patients, and increases in
      the standard of living. As a research-based and high-tech sector, the
      pharmaceutical industry depends highly upon technological innovation, especially
      the spatial diffusion of technologies from the perspective of economic geography.
      In this context, an analysis of technology flowing between regions is of great
      significance for the investment in a regional market. This article differs from
      previous studies by focusing on geographic patterns of pharmaceutical technology
      transfer captured by patent licensing in China, which are further used to analyze
      investment strategies. The research sample is composed of all pharmaceutical
      patent licenses filed with the State Intellectual Property Office of China from
      January 1, 2009, through December 31, 2012. As a result, a geographic network of
      pharmaceutical technology diffusion in China could be visualized, and province
      level regions were ranked and classified into 3 types-input, output, and balance
      by various network indicators. Finally, potential investment strategies on
      different types of regions are recommended for firms abroad, technology holders,
      contract research organizations, and technology agencies.

PMID- 30227502
TI  - Evolving Role of Pharmacists in Care Coordination: A National Survey.
AB  - Care coordination focuses on interdisciplinary collaboration to provide high
      quality health care at reduced costs. Pharmacists have integrated themselves into
      collaborative teams and are expected to continue expanding their role in order to
      provide services to patients throughout the continuum of care. This report
      details an online survey that was used to determine whether pharmacists envision
      an expanded role in care coordination in the next 5 years, in light of health
      care reform and the US Patient Protection and Affordable Care Act (2010), and to
      determine the types of tools pharmacists will need to better facilitate care
      coordination. Results indicate that pharmacists predict an expanded role in care
      coordination in the near future as well as the need for innovative tools to aid
      in this expansion, especially electronic tools such as mobile technology and
      social media.

PMID- 30227503
TI  - Evaluation of Assay Sensitivity and the Concentration-Effect Relationship of
      Moxifloxacin in a QT/QTc Study in Japan.
AB  - To investigate the potential for a QT/QTc study in Japan, a randomized, single
      blind, crossover study was conducted using moxifloxacin in 64 healthy Japanese
      male volunteers. A 12-lead Holter electrocardiogram was used to test a relatively
      small population at each of 4 incorporated clinical research units to confirm the
      assay sensitivity and efficiency. Moxifloxacin (400 mg) significantly prolonged
      QT intervals, as previously reported, with small variations in this study. In
      addition, the placebo-adjusted mean QTcF changes from predose baseline showed
      that the lower bounds of the 1-sided 95% confidence interval exceeded 5
      milliseconds at all of the clinical research units. The data also indicated
      statistically significant concentration-QT relationships in 3 of the 4 research
      units by separate analysis. These findings and the small amount of variability in
      this study suggest the feasibility of conducting a high-quality QT/QTc study in
      Japan.

PMID- 30227504
TI  - Reply to Letter to the Editor: Local Evaluation and Blinded Central Review
      Comparison a Victim of Meta-analysis Shortcomings.

PMID- 30227505
TI  - The Effectiveness of the Summary of Product Characteristics (SmPC) and
      Recommendations for Improvement.
AB  - One of the roles of the Summary of Product Characteristics (SmPC) is to provide
      information for health professionals. The objective of this work was to
      understand the effectiveness of the SmPC document in communicating essential
      information to prescribers. The process of user testing, widely used to test
      information for patients, was applied. First, 30 general practitioners were
      involved in the testing of the SmPC for Lariam, an antimalarial drug. As user
      testing is an iterative process, 15 points of information in the original SmPC
      were tested in 3 rounds of 10 participants. The document was revised between
      rounds according to the results; good practice in information writing and design
      was used. Next, the SmPC for CellCept, an immunosuppressant, was tested in 20
      senior hospital doctors. Again, the document was revised between rounds,
      according to the results, with revisions also taking account of findings from the
      Lariam testing related to the general structure of SmPCs. Of the 15 points of
      information tested, for the original Lariam SmPC, 6 points of information met the
      target of 90% to find, and 90% of those to understand, whereas for the final
      version of the CellCept SmPC, 11 points of information met this target.
      Qualitative comments showed that in their current format, SmPCs are of low
      perceived value to prescribers and are not central to the clinicians' prescribing
      behavior. Current content and presentation of SmPCs, while meeting regulatory
      approval standards, contribute little to the safe and effective use of medication
      in practice. Key recommendations include revising and simplifying the heading
      structure and making the headings more visible, adding a "Key Information"
      summary at the start, using simpler language, and adding bullet points for
      listings.

PMID- 30227506
TI  - Analysis of Medical Information Responses to Unsolicited Health Care Worker
      Inquiries Submitted via Sales Representatives or Customers Directly.
AB  - Unsolicited inquiries for off-label medical/product information are the focus of
      compliance monitoring programs as described in regulatory guidance published by
      the US Office of the Inspector General (OIG) and the US Food and Drug
      Administration (FDA). Pharmaceutical industry medical information departments
      (PIMIDs) are encouraged to monitor and report on patterns of activity, including
      the source and frequency and types of off-label inquiries received. Especially of
      interest are unsolicited off-label inquiries triaged via sales representatives.
      By tagging all response documents with "compliance topic" codes that reflect the
      type of off-label inquiry (eg, unapproved indications/uses, more detailed or
      extended data, adverse events, etc) and specifically tracking for the inquiry
      source route, our PIMID was able to analyze and compare customer inquiries
      including those triaged by sales representatives. In an analysis of all inquires
      (n = 20,213) received over a 2-year period (2010-2011), it was observed that
      inquires submitted by sales representatives after unsolicited health care worker
      (HCW) requests accounted for only 14.8% of requests overall. Questions related to
      "off-label indications/uses" (ie, compliance topic of most interest to regulatory
      agencies) accounted for 5.8% of all inquiries and were almost equally distributed
      in number between sales representative triage and HCW direct calls to the PIMID.
      For the set of sales representative triage submissions in 2010 and 2011, the "off
      label indications/uses" category accounted for 15.3% to 20.5%, respectively, and
      was statistically significant ( P < .001) for the rate of 4.8% to 8.1% observed
      collectively for all customer sources. In most cases, there were similarities in
      questions asked (top 5 ranking) and their geographical source for sales
      representative triage versus customers directly.

PMID- 30227507
TI  - Clinical Data for Informed Medication Use in Pregnancy: Strengths, Limitations,
      Gaps, and a Need to Continue Moving Forward.
AB  - The objective of this paper is to explore the strengths, weaknesses, gaps, and
      needs in research on medication use in pregnancy, where opportunities have been
      bypassed to develop standards and collaborations for collecting data to better
      understand how medications can impact clinical outcomes in pregnant women and
      developing fetuses. The availability of existing data and the methods of its
      capture are reviewed, including registries, claims and health record databases,
      and meta-analyses. The paper focuses on why these efforts have not fundamentally
      provided benefit-risk information and clinical treatment algorithms for
      medication use in pregnant women. Methodological issues, such as lack of
      standardization and central data collection, are discussed. Common barriers are
      examined, including a lack of awareness and education, cultural hurdles,
      collaboration deficiency, and an insufficient development of new data collection
      methods.

PMID- 30227508
TI  - Circadian Variation and Baseline Definition in Parallel-Group Thorough QT
      Studies.
AB  - For thorough QT (TQT) studies employing a parallel-group design, there has been a
      clear regulatory preference for the use of time-matched, rather than time
      averaged, baseline values to account for circadian variation when estimating the
      magnitude of the drug effect on the QT interval. In this paper, both historical
      data from parallel-group TQT studies and simulated data from assumed circadian
      models are utilized to comprehensively assess the performance characteristics of
      3 repeated-measures analysis of covariance models. The results indicate that each
      analysis model performs adequately in the absence of an observed time-matched
      baseline imbalance between the treatment groups. However, the analysis model with
      time-matched baseline as a covariate performs poorly under the setting of an
      observed time-matched baseline imbalance between the treatment groups. The
      analysis model with time-averaged baseline as a covariate and the analysis model
      with both time-matched and time-averaged baselines as covariates provide unbiased
      estimates of the treatment difference and properly control the type I error rate,
      regardless of an observed time-matched baseline imbalance or within-patient
      variation in circadian parameters.

PMID- 30227510
TI  - Editor-in-Chief's Commentary: Collaborate to Innovate.

PMID- 30227509
TI  - Further Understanding of the International Index of Erectile Function at 15+
      Years: Confirmatory Factor Analysis and Multidimensional Scaling.
AB  - The objective of this study was to describe confirmatory factor analysis (CFA)
      and multidimensional scaling (MDS) on the International Index of Erectile
      Function (IIEF) to confirm the structure and to enrich understanding of the IIEF,
      thereby heightening appreciation of the factors and responses underlying sexual
      functioning for men with erectile dysfunction. Baseline, end of double-blind, and
      end of open-label data sets were derived from all data from 2 previously
      published sildenafil trials. For the CFA model, an acceptable fit of the data was
      shown for each data set, as indicated by a Bentler comparative fit index >0.9,
      statistically significant path coefficients ( t values >1.96), and (except for
      IIEF item 6 at baseline) statistically significant standardized path coefficients
      >=0.4. For MDS modeling, the distance matrix created for each data set, based on
      polychoric correlations, interpreted relationships between the IIEF items in 2
      dimensional space across the "sexual intercourse interference" dimension
      (horizontal axis) and the "sexual satisfaction" dimension (vertical axis). The 5
      factor structure of the IIEF was confirmed by CFA and enriched with visual
      interpretation by MDS.

PMID- 30227511
TI  - Essential Medication Information for Patients: Ensuring Access.
AB  - The US Food and Drug Administration (FDA) is developing a new framework to
      provide patients with quality, up-to-date prescription product information that
      will promote the safe use of prescribed medication. The goal of this new Patient
      Medication Information is to provide patient-oriented information for each
      prescription product. Described in this article are the efforts of the FDA to
      help ensure that patients receive essential prescription medication information.

PMID- 30227512
TI  - On the Importance in Clinical Trials That Critical Regions for Comparing 2
      Independent Proportions Must Be Barnard Convex Sets.
AB  - The non-inferiority and superiority (NI/S) formulations to evaluate a new
      treatment are frequently used in active-controlled clinical trials. A key
      assumption for the NI/S statistical tests that compare 2 independent proportions
      is that corresponding critical regions are Barnard convex sets. This assumption
      allows significant reduction in the computation time required to calculate test
      sizes for these tests. This study presents arguments that both types of testing
      procedures (NI/S) require the corresponding critical regions to be Barnard convex
      sets. Otherwise, these tests may become meaningless. Notably, the critical
      regions of the well-known Blackwelder and Hauck-Anderson tests are not Barnard
      convex sets for many sample sizes.

PMID- 30227513
TI  - Pharmacovigilance Legislation: The Impact of What Is Happening in Europe.
AB  - Pharmaceutical companies, regulatory agencies, and contract service organizations
      are managing substantial and ongoing changes to pharmacovigilance legislation in
      the European Economic Area, and penalties for noncompliance are potentially
      large. Given that the majority of pharmaceutical companies and contract service
      organizations have global reach, the impact of this change is being felt far
      beyond the boundaries of the European Economic Area.

PMID- 30227514
TI  - Evolving Global Regulatory Science Through the Voluntary Submission of Data: A
      2013 Assessment.
AB  - Regulatory science, the science of developing new tools, standards, and
      approaches to assess the safety, efficacy, quality, and performance of regulated
      medical products, has advanced over time due to a number of factors. The FDA, the
      EMA, and the Pharmaceuticals and Medical Devices Agency (PMDA) have recently
      formalized voluntary data submission processes for the regulatory "qualification"
      of novel tools and methodologies for use in drug development. While recognizing
      that other mechanisms exist within the research community for driving scientific
      consensus on novel tools and methodologies, this article focuses on the formal
      regulatory process that addresses a tool's acceptability for incorporation by any
      sponsor into novel medical product development. Guidances, regulatory
      qualification opinions, and publications were reviewed to allow a systematic
      comparison of the process, content, and volume of submissions at the FDA, EMA,
      and PMDA. Qualification of new tools by regulatory agencies and subsequent
      adoption by drug developers are anticipated to speed therapeutic development for
      patients in need, build scientific consensus as to the usefulness and readiness
      of novel methodologies for understanding disease and therapeutic development, and
      decrease uncertainty between the regulators and sponsors regarding the
      appropriate application of new tools.

PMID- 30227515
TI  - A Continual Reassessment Method With Cohort Size Adaptation Based on Bayesian
      Posterior Probabilities in Phase I Dose-Finding Studies.
AB  - In phase I cancer studies, the maximum tolerated dose (MTD) is estimated by
      gradually increasing dose levels while accumulating safety information. Recently,
      Bayesian dose-finding methods such as the continual reassessment method (CRM)
      have gained popularity. Due to the lack of safety information, phase I studies on
      new drugs must start at doses low enough that efficacy is not expected but safety
      is certain up to an acceptable level. To reach the MTD with fewer patients, a 2
      stage method has been proposed that enrolls only a single patient at each dose
      level until the first dose-limiting toxicity is observed. If the study drug is
      less toxic, it may require many cohorts to complete the study and thus may lead
      to a longer study period. In this paper, the authors propose a new CRM with
      cohort size adaptation to reduce the number of cohorts without reducing the
      accuracy of MTD selection. The cohort size is determined based on the Bayesian
      posterior probabilities computed during a study. Simulation studies show that the
      proposed method reduced the number of cohorts compared with the 2-stage method
      while still yielding a comparable probability of selecting the MTD correctly.

PMID- 30227516
TI  - Prevalence and Therapeutic Classifications of FDA-Approved Prescription Drugs
      With Boxed Warnings.
AB  - PURPOSE: To characterize and determine the prevalence of drugs with boxed
      warnings (BXWs) based on a review of structured product labels (SPLs) available
      on the National Library of Medicine (NLM) DailyMed website. METHODS: A cross
      sectional review was conducted of SPLs with BXWs for human prescription drugs on
      the NLM DailyMed website in July 2012. The presence of a BXW in the DailyMed
      version of the SPL was validated by cross-referencing a corresponding label on
      the FDA website. The SPLs were organized into drug groups, and descriptive
      statistics were used to determine the proportion of SPLs and drug groups
      associated with a validated BXW. The top therapeutic classes of drugs with BXWs
      were determined as well as the percentage of the top 100 BXW-associated drugs
      used in US hospitals and retail settings in 2012. RESULTS: Findings revealed that
      35% (n = 4940/14,264) of drug labels on DailyMed and 35% (n = 650/1848) of the
      drug groups created were associated with a validated BXW. Central nervous system
      agents, antineoplastic agents, and cardiovascular drugs were the most common
      therapeutic classes. In 2012, 39% of the top 100 drugs were associated with a
      BXW.

PMID- 30227517
TI  - Editor-in-Chief's Commentary: Innovation in Publications.

PMID- 30227518
TI  - A Review of Regulatory Mechanisms Used by the WHO, EU, and US to Facilitate
      Access to Quality Medicinal Products in Developing Countries With Constrained
      Regulatory Capacities.
AB  - Adequate medicine regulation requires nations to establish robust regulatory
      agencies that will subject all pharmaceutical products to pre- and postmarketing
      evaluation. These agencies are essential for any country wishing to ensure that
      the medicinal products it authorizes for use in its territory meet
      internationally agreed standards of safety, quality, and efficacy. Many
      developing nations, however, lack regulatory systems that can guarantee this set
      of requirements. As a result, almost all of these nations tend to rely on
      regulatory decisions made by well-resourced institutions, particularly the US
      Food and Drug Administration, the European Medicines Agency, and the World Health
      Organization. In this paper, the authors review the objectives, strengths, and
      weaknesses of some key regulatory initiatives instituted by these bodies to
      facilitate product registration in developing countries with constrained
      regulatory capacities.

PMID- 30227519
TI  - Medical Information Contact Centers: Challenges and Best Practices.
AB  - Today's medical information contact centers face a number of complex challenges.
      A recent survey of the DIA Medical Communications Special Interest Area Community
      (SIAC) members indicated that budgetary pressures, employee training, preparing
      for product launches, and ensuring business continuity are all concerns for the
      majority of contact centers. Additionally, more than one third of contact centers
      mentioned mergers and acquisitions. This article will review the results of the
      survey and discuss best practices for addressing the 3 most common topics noted
      in the survey: budget, training, and supporting product launches. The article is
      intended as a resource for contact center managers and to help encourage the
      sharing of best practices within the industry.

PMID- 30227520
TI  - A Practical Estimation Method for Analyzing Adverse Drug Reactions Using Data
      Mining.
AB  - This study aimed to determine the potentially severe chemical properties of drugs
      that can cause adverse drug reactions (ADRs) such as erythema multiforme (EM),
      Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) by using a
      data mining method. The study data were extracted from the Adverse Event
      Reporting System database of the FDA. EM was considered a mild reaction, and SJS
      and TEN were considered severe reactions. In this study, a new concept termed the
      "risk of aggravation" (ROA) was defined as whether a certain drug is more likely
      to cause severe adverse reactions than mild ones. Partial least squares and
      logistic regression analysis were applied using binary response variable ROAs.
      These analyses correctly predicted 50 of the 72 drugs associated with SJS and/or
      TEN and 28 of the 38 drugs associated with EM using binary chemical descriptors
      that are the same as those using the metric chemical descriptors.

PMID- 30227521
TI  - The Effect of Market-Based Economic Factors on the Adoption of Orphan Drugs
      Across Multiple Countries.
AB  - Orphan drugs are designed to treat rare disease. Multiple countries have approved
      regulations that support the creation of new orphan drugs. The regulations
      directly and indirectly affect orphan drug markets and contribute to classifying
      a country as being more or less market based. A more market-based country is
      recognized as functioning closest to free market principles, where the actions of
      supply, demand, and pricing operate with minimal government involvement. However,
      little information exists on how country market differences affect the adoption
      of these orphan drugs. This study argues that relationships exist between country
      market-based economic factors and the adoption of orphan drugs. This research
      uses a combination of qualitative and quantitative methods, drawing on orphan
      drug adoption of 13 marketed orphan drugs in France, Germany, Spain, the UK, and
      the US. Results show a statistically significant but negative relationship
      between the degree to which a country is market based and the adoption of orphan
      drugs. Results suggest that governments and regulators in less market-based
      countries support market factors that result in a more efficient delivery of
      orphan drug products to patients with rare diseases.

PMID- 30227522
TI  - Cycle Time Metrics for Multisite Clinical Trials in the United States.
AB  - Conducting randomized controlled trials entails a prolonged, costly study start
      up (SSU) process that may create significant delays. Optimizing the operational
      aspects of multisite trials requires identifying benchmarks in the SSU process
      and the potential delays associated with them. We engaged in a collaborative
      effort to identify and describe key SSU intervals that correspond with necessary
      procedures and processes for activating multisite clinical trials in the US.
      After developing definitions for SSU benchmarks and obtaining data from research
      coordinating entities, we identified factors that were significantly associated
      with reduced cycle times, including the use of central institutional review
      boards for study approval and status as a private practice or independent
      research site. However, small sample sizes and large proportions of missing data
      hamper the interpretability of our results. Future development of standard
      measures of SSU efficiency will be critical to analyzing and improving study
      initiation processes at US research sites.

PMID- 30227523
TI  - Evaluation of Blinded Independent Central Review of Tumor Progression in Oncology
      Clinical Trials: A Meta-analysis.
AB  - Use of blinded independent central review (BICR) has become more common in
      oncology phase 3 trials as progression-free survival (PFS) has been increasingly
      used as an endpoint for regulatory approval. Since PFS is primarily a
      radiographic endpoint, BICR has been implemented to assess and reduce potential
      bias in the local evaluation (LE) of PFS. Recent publications note an agreement
      between LE and BICR of the ultimate reported PFS treatment effect, which
      questions the need for costly and time-consuming complete-case BICR of PFS. A
      meta-analysis was conducted to systematically evaluate the relationship between
      BICR- and LE-assessed PFS based on FDA's regulatory experience from 2005 to
      present. Our results support the claim that a complete review of all radiographs
      by BICR may not be necessary for oncology trials, and alternative methods should
      be explored to evaluate bias. One potential alternative is to use BICR as an
      audit tool to detect evaluation bias in LE assessments.

PMID- 30227524
TI  - Safety Information From Spontaneous and Literature Adverse Reaction Reports: A
      Comparison.
AB  - Marketing authorization holders should report adverse drug reactions (ADRs)
      derived from spontaneous case reports and literature for their medicinal products
      to competent authorities. Yet the difference in quality of data from both sources
      has never been analyzed. To this end, YES Pharmaceutical Development Services in
      cooperation with the German Medicines Manufacturers Association has conducted an
      analysis examining more than 25,100 spontaneous and literature cases that
      occurred between 2007 and 2008. Reporting rates of ADRs for specific drug
      substances (DSs), expectedness, and the system organ class (SOC) referred to were
      examined. It was found that the distribution of ADRs to specific SOCs differs
      between both groups for selected DSs. For more than 37% of the DSs being
      evaluated, a difference of 10% or more regarding reporting rates of unexpected
      ADRs was observed between both groups. These findings underline the substantial
      importance of regular literature reviews in addition to the spontaneous reporting
      system for a sufficient safety assessment of medicinal products.

PMID- 30227525
TI  - Medical Information Specialists: Benchmarks in Practice.
AB  - A gap exists for global benchmarking data on medical information specialists
      across the pharmaceutical industry. As such, the purpose of this study was to
      benchmark the practices and training of medical information specialists in the
      pharmaceutical industry. Results collected will be used to identify training and
      background of current medical information specialists as well as to describe
      current medical information-related responsibilities. A 23-item, electronic
      survey instrument was sent to individuals with an interest in or association with
      medical communications, medical information, and/or medical science liaisons
      through the DIA database. A total of 61 complete and 29 incomplete responses were
      received. Results indicated that similarities exist in medical information
      specialists' positions regarding organization and reporting structure, job
      requirements and credentials, core responsibilities, and even identified
      challenges. These findings may help medical information specialist organizations
      better compare their own practices with those of other groups in the
      pharmaceutical industry.

PMID- 30227526
TI  - Life Cycle Modeling and Simulation: Current Practice and Future Impact on Health
      Care Innovation and Delivery.
AB  - Modeling and simulation is poised to transform drug development across the entire
      life cycle from discovery to commercialization. For the biopharmaceutical
      industry, this transformation will enable knowledge-based decision making and
      foster new collaborative ways of working that will translate into more high-value
      treatments and increased development efficiencies. In the health care arena,
      where value for money is paramount, modeling and simulation will inform future
      health care planning and practice.

PMID- 30227527
TI  - Expanding Consumer Medication Access: The Time Is Now.
AB  - The US FDA is proposing an expanded over-the-counter (OTC) medication policy to
      improve patient access to medications under the supervision of a pharmacist.
      Higher levels of medication access via multiple medication categories are common
      in other industrialized nations. Pharmacists are well trained and widely
      available. Expanding medication access can help alleviate the physician shortage
      by directing patients with appropriate health conditions that can be managed with
      medication to community pharmacists. Examples include migraine headaches and
      seasonal allergies, which have a significant impact on patients' quality of life
      and work productivity. Clinically relevant medications and dosages should be
      selected. Medication use guidelines should not be so restrictive as to defeat the
      policy intent. The proposed FDA policy is a long-overdue change that will help
      optimize available health personnel resources for patient care.

PMID- 30227528
TI  - Health Care Professionals' Expectations of the Medical Science Liaison: A Blinded
      Survey.
AB  - The role of the medical science liaison (MSL) within the industry is evolving yet
      well established. Reports of MSL activities have uniformly been from the view of
      the pharmaceutical company. This report describes the desired activities from the
      perspective of the health care professional (HCP) using a blinded, 2-phase survey
      method. The first phase was an online quantitative survey conducted among key
      opinion leaders (KOLs) in the academic and practicing fields for diabetes
      research and treatment who have met with an Amylin MSL in the past 6 months. The
      second phase consisted of 1-on-1 telephone interviews with a subset of
      participants from phase 1 to better understand what KOLs want and need from MSLs,
      to explore how MSLs can add value to their interaction with KOLs, and to
      understand how Amylin MSLs are performing. The research evaluated a number of
      questions, including how KOLs view the MSLs and the value they bring to the KOLs.
      There were 116 KOLs who completed the online survey and who were considered
      qualified completers. Diabetes MSLs are a valuable resource to KOLs. They must
      first and foremost present themselves as ethical and unbiased. They help KOLs
      stay up to date on industry information and happenings, saving time for the busy
      KOL. The KOL's key information needs are around pipeline and research. They would
      like to get to know their MSLs better, to understand their background and
      experience, and to see them more often.

PMID- 30227529
TI  - Quality by Design in Clinical Trials: A Collaborative Pilot With FDA.
AB  - The quality of a clinical trial can be assessed by whether the trial meets the
      needs of its various customers, as well as by its freedom from critical
      deficiencies or errors. In order to ensure the quality of a clinical trial, it is
      therefore important to conduct quality planning in parallel with the process to
      design and prior to the conduct of the trial. Quality planning consists of
      prospectively establishing quality goals and developing the products and
      processes required to deliver a quality trial. This article describes the quality
      planning process conducted by a pharmaceutical sponsor for a clinical trial and
      the pilot review of the resulting integrated quality management plan by the FDA.
      This pilot demonstrates the usefulness of this process to enable alignment
      between sponsors and regulators concerning quality in clinical trials.

PMID- 30227530
TI  - Validation of QT Interval Correction Methods When a Drug Changes Heart Rate.
AB  - The QT interval is correlated with heart rate; therefore, the QT interval is
      usually corrected by heart rate when drug-induced QT effect is studied.
      Currently, there are many correction methods that use either fixed or data-driven
      approaches. The effectiveness of correction methods depends on many factors and
      varies from study to study. Statistical validation and comparisons need to be
      performed to determine the most appropriate correction method for each study. We
      examined different validation methods and explored a new approach to use when the
      testing drug changes heart rate.

PMID- 30227531
TI  - Drug Information Activity and Nonprescription Requests Over the Malaysian
      Counter.
AB  - Providing drug information has become one of the essential job functions of a
      community pharmacist. To ensure the availability of up-to-date information,
      pharmacists should have access to reliable drug information. The current study
      was an effort to explore the use of drug information resources at a community
      pharmacy in Penang Island, Malaysia. This study also explores nonprescription
      requests, with a special emphasis on pharmacists' agreement to dispense medicines
      without a prescription. A cross-sectional study was performed among the community
      pharmacists practicing in 3 populous areas of Penang Island. Face-to-face
      interviews were conducted using a 24-item questionnaire. The response rate was
      67.3%. Online drug information, compared with other resources, was preferred by a
      majority of pharmacists (n = 19, 51.4%). Of the pharmacists, 28 (75.7%) mentioned
      that patients often make a nonprescription drug request for anti-inflammatory
      agents, painkillers, and medicines for cough and flu. In about 59.5% of the
      cases, pharmacists dispensed the requested medicine without question. Most of the
      pharmacists stated they have dispensed painkillers, creams and ointments,
      antifungals, body tonics, and inhalers without prescription.

PMID- 30227532
TI  - Changes to Prescription Drug Pediatric Labeling: Awareness by Practicing
      Pediatricians.
AB  - The US Congress and the US Food and Drug Administration encouraged studies in
      children so that the labeling information about pediatric use could be updated
      for pharmaceutical products. Pediatricians receive this updated labeling
      information through many different sources. A pilot survey was conducted to
      determine what source pediatricians use to learn about this updated information
      and whether and when they learned of specific changes. It appears that most
      pediatricians did not know that there had been recent changes in pediatric drug
      labels, although changes to drugs that were used more commonly in practice were
      more likely to be known.

PMID- 30227533
TI  - Drug Information: Prescribers' Need for and Access to Drug Information Resources
      in Ethiopia.
AB  - Rational and cost-effective prescription of drugs requires up-to-date and readily
      accessible drug information (DI). Availability of and access to DI resources are
      major factors that affect quality of prescription. The aim of the study was to
      assess prescribers' DI needs and access to DI resources in Ethiopia. A facility
      based, cross-sectional, quantitative study was conducted from February to April
      2011 in 4 selected public health facilities in southwest Ethiopia. Data on areas
      of DI needs, access to DI resources, and attitudes of prescribers toward DI
      services were collected using a structured, self-administered questionnaire. The
      study population consisted of 410 of 447 initially contacted prescribers. The
      majority of the prescribers (93.4%) explained their needs for DI services. About
      32.4% of the participants do not frequently refer to DI resources mainly due to
      the difficulty of acquiring the required information promptly and/or because they
      do not have access to DI resources. Compared with participants from a health
      center, participants from specialized referral, zonal, and district hospitals
      were found to be 6 (adjusted odds ratio [AOR], 5.81; 95% confidence interval
      [CI], 2.77-12.20), 5 (AOR, 4.77; 95% CI, 2.43-9.38), and 4 (AOR, 4.00; 95% CI,
      1.50-10.66) times more likely to consult DI resources, respectively. Lack of
      access to DI resources and difficulty in acquiring the required information on
      time were the main reasons that prescribers gave for not frequently referring to
      DI resources. DI services should be established and expanded in health
      facilities.

PMID- 30227534
TI  - Factors Related to Regulatory Approval of Late-Stage Development Compounds:
      Analysis of Japanese Pharmaceutical Company Activities, 1995-2007.
AB  - Japanese pharmaceutical companies invest resources in their internal research and
      development (R&D) activities and in-licensing activities especially from Western
      companies, for the local market. The objective of this research is to investigate
      the fate of late-stage compounds developed by them and to identify company
      profiles and compound characteristics that could relate to regulatory
      approvability. Using publicly available information for late-stage compounds that
      were developed by Japanese companies in 1995-2007, logistic regression analysis
      was conducted to investigate the company characteristics and regulatory approval
      ratio, as well as compound characteristics and probability of approval, for late
      stage development compounds. Compound approvability was correlated to the time
      when the compound was developed (ie, the approval ratio of compounds in phase 3
      or later in 1995-1998 was lower than that in 2001 or later); also, in-licensed
      compounds from large pharmaceutical companies received a higher approval ratio.
      Company size and R&D expenses were not correlated to their approval ratio.

PMID- 30227535
TI  - Sample Size Calculation for Bioequivalence Studies Assessing Drug Effect and Food
      Effect at the Same Time With a 3-Treatment Williams Design.
AB  - The US Food and Drug Administration issued a guidance in 2002, "Food-Effect
      Bioavailability and Fed Bioequivalence Studies," in which it states "in addition
      to a BE [bioequivalence] study under fasting conditions, we recommend a BE study
      under fed conditions for all orally administered immediate-release drug products"
      for abbreviated new drug applications. This statement involves 3 studies: a BE
      study under fasting status, a food-effect (FE) study, and a BE study under fed
      status. In practice, when it is known that there is no FE with a reference ( R)
      formulation, a sponsor may choose to run a BE study that assesses the drug effect
      and food effect with a test ( T) formulation in a single study that includes 3
      treatments: R formulation at fasting status, T formulation at fasting status, and
      T formulation at fed status. Such a study combines the fasting BE study and the
      FE study on the T formulation and may justify the waiver of the fed BE study if
      conclusions can be made that there is no FE with the T formulation after this
      combined study completes. This article discusses how to calculate the sample size
      for this kind of study with different primary analysis models. Also discussed are
      (1) sample size calculations with more general BE studies and (2) how they can be
      implemented using commercial software in a standard 2-treatment, 2-period, and 2
      sequence crossover design, as well as (3) a related practical issue of how to
      retrieve residual intrasubject mean squared error from historical summary results
      in the literature.

PMID- 30227536
TI  - Re: Artifact-Free In-Stent Lumen Visualization by Standard Magnetic Resonance
      Angiography Using a New Metallic Magnetic Resonance Imaging Stent.

PMID- 30227538
TI  - Re: 90-Day Complication Rate in Patients Undergoing Radical Cystectomy with
      Enhanced Recovery Protocol: A Prospective Cohort Study.

PMID- 30227537
TI  - Re: Long-Term Efficacy of Holmium Laser Enucleation of the Prostate in Patients
      with Detrusor Underactivity or Acontractility.

PMID- 30227539
TI  - Re: Functional Outcomes after Transurethral Resection of the Prostate in Nursing
      Home Residents.

PMID- 30227540
TI  - Re: Efficacy and Safety of Silodosin in the Treatment of Lower Urinary Tract
      Symptoms in Elderly Men Taking Antihypertensive Medications.

PMID- 30227541
TI  - Re: Efficacy and Safety of Tadalafil 5 mg Once Daily in the Treatment of Lower
      Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia in Men Aged
      >=75 Years: Integrated Analyses of Pooled Data from Multinational, Randomized,
      Placebo-Controlled Clinical Studies.

PMID- 30227542
TI  - Re: Pathophysiology of Nocturnal Lower Urinary Tract Symptoms in Older Patients
      with Urinary Incontinence.

PMID- 30227544
TI  - Re: Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic
      Review and Meta-Analysis by the European Association of Urology Urological
      Infection Guidelines Panel.

PMID- 30227543
TI  - Re: Imaging Appearance of Fibrosing Diseases of the Retroperitoneum: Can a
      Definitive Diagnosis be Made?

PMID- 30227545
TI  - Re: Review of Advances in Uroprotective Agents for Cyclophosphamide- and
      Ifosfamide-Induced Hemorrhagic Cystitis.

PMID- 30227546
TI  - Re: Chronic Prostatitis and Comorbid Non-Urological Overlapping Pain Conditions:
      A Co-Twin Control Study.

PMID- 30227547
TI  - Re: Robotic Ureteral Reconstruction Using Buccal Mucosa Grafts: A Multi
      Institutional Experience.

PMID- 30227548
TI  - Re: A Prospective Randomised Comparison between the Transperitoneal and
      Retroperitoneoscopic Approaches for Robotic-Assisted Pyeloplasty in a Single
      Surgeon, Single Centre Study.

PMID- 30227549
TI  - Re: Real-World Observational Results from a Database of 48 Million Men in the
      United States: Relationship of Cardiovascular Disease, Diabetes Mellitus and
      Depression with Age and Erectile Dysfunction.

PMID- 30227550
TI  - Re: Objective Measurements of the Penile Angulation are Significantly Different
      than Self-Estimated Magnitude among Patients with Penile Curvature.

PMID- 30227551
TI  - Re: A Worldwide Survey on Peyronie's Disease Surgical Practice Patterns among
      Surgeons.

PMID- 30227552
TI  - Re: Safety and Feasibility of Platelet Rich Fibrin Matrix Injections for
      Treatment of Common Urologic Conditions.

PMID- 30227553
TI  - Re: Sonographic Patterns of Peyronie's Disease in Patients with Absence of
      Palpable Plaques.

PMID- 30227554
TI  - Re: Paternal Age: Negative Impact on Sperm Genome Decays and IVF Outcomes after
      40 Years.

PMID- 30227555
TI  - Re: Effect of the Male Factor on the Clinical Outcome of Intracytoplasmic Sperm
      Injection Combined with Preimplantation Aneuploidy Testing: Observational
      Longitudinal Cohort Study of 1,219 Consecutive Cycles.

PMID- 30227556
TI  - Re: Sperm Selection by Thermotaxis Improves ICSI Outcome in Mice.

PMID- 30227557
TI  - Re: Usefulness of Testicular Volume, Apparent Diffusion Coefficient, and
      Normalized Apparent Diffusion Coefficient in the MRI Evaluation of Infertile Men
      with Azoospermia.

PMID- 30227558
TI  - Re: Attitudes towards "Disorders of Sex Development" Nomenclature among Affected
      Individuals.

PMID- 30227559
TI  - Re: Unexpected Ethical Dilemmas in Sex Assignment in 46,XY DSD Due to 5-Alpha
      Reductase Type 2 Deficiency.

PMID- 30227560
TI  - Re: Air Pollution and Human Sperm Sex Ratio.

PMID- 30227561
TI  - Re: Ascending Testis after Repair of Pediatric Inguinal Hernia and Hydrocele: A
      Misunderstood Operative Complication.

PMID- 30227562
TI  - Re: Testicular Function during Puberty and Young Adulthood in Patients with
      Klinefelter's Syndrome with and without Spermatozoa in Seminal Fluid.

PMID- 30227563
TI  - Re: A Cost Comparison for Telehealth Utilization in the Kidney Transplant
      Waitlist Evaluation Process.

PMID- 30227564
TI  - Re: Association between Testicular Microlithiasis and Testicular Neoplasia: Large
      Multicenter Study in a Pediatric Population.

PMID- 30227566
TI  - Re: Association of the Affordable Care Act Medicaid Expansion with Access to and
      Quality of Care for Surgical Conditions.

PMID- 30227565
TI  - Re: Use of Alternative Medicine for Cancer and its Impact on Survival.

PMID- 30227567
TI  - Re: Using Medicare Claims to Examine Long-Term Prostate Cancer Risk of
      Finasteride in the Prostate Cancer Prevention Trial.

PMID- 30227568
TI  - Re: Participation and Dropout in the Bundled Payments for Care Improvement
      Initiative.

PMID- 30227569
TI  - Re: Trends in Penile Prosthetics: Influence of Patient Demographics, Surgeon
      Volume, and Hospital Volume on Type of Penile Prosthesis Inserted in New York
      State.

PMID- 30227570
TI  - Re: Ambicor 2-Piece Inflatable Penile Prosthesis: Who and How?

PMID- 30227571
TI  - Re: The Extra-Tunical Grafting Procedure for Peyronie's Disease Hourglass and
      Indent Deformities.

PMID- 30227572
TI  - Re: Two are no Different than One: Ureteral Duplication Appears to Have no Effect
      on Ureteroscopy Outcomes.

PMID- 30227573
TI  - Re: Use of the Ureteral Access Sheath during Ureteroscopy: A Systematic Review
      and Meta-Analysis.

PMID- 30227574
TI  - Re: The Transgluteal Approach to Shockwave Lithotripsy to Treat Distal Ureter
      Stones: A Prospective, Randomized, and Multicenter Study.

PMID- 30227575
TI  - Re: Mini vs Standard Percutaneous Nephrolithotomy for Renal Stones: A Comparative
      Study.

PMID- 30227576
TI  - Re: Pathological Heterogeneity in Sporadic Synchronous Renal Tumors: Is the
      Histological Concordance Predictable?

PMID- 30227577
TI  - Re: Incidence of T3a Up-Staging and Survival after Partial Nephrectomy: Size
      Stratified Rates and Implications for Prognosis.

PMID- 30227578
TI  - Re: Results of a Randomised Controlled Trial Comparing Intravesical
      Chemohyperthermia with Mitomycin C versus bacillus Calmette-Guerin for Adjuvant
      Treatment of Patients with Intermediate- and High-Risk Non-Muscle-Invasive
      Bladder Cancer.

PMID- 30227579
TI  - Re: Familial Cancer Clustering in Urothelial Cancer: A Population-Based Case
      Control Study.

PMID- 30227580
TI  - Re: MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

PMID- 30227581
TI  - Re: Short-Term Effects of Transdermal Estradiol in Men Undergoing Androgen
      Deprivation Therapy for Prostate Cancer: A Randomized Placebo-Controlled Trial.

PMID- 30227582
TI  - Re: Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer
      Mortality: The CAP Randomized Clinical Trial.

PMID- 30227583
TI  - Re: A Mucosal Imprint Left by Prior Escherichia coli Bladder Infection Sensitizes
      to Recurrent Disease.

PMID- 30227584
TI  - Re: Identification of 19 New Risk Loci and Potential Regulatory Mechanisms
      Influencing Susceptibility to Testicular Germ Cell Tumor.

PMID- 30227585
TI  - Re: E-Cigarette Smoke Damages DNA and Reduces Repair Activity in Mouse Lung,
      Heart, and Bladder as Well as in Human Lung and Bladder Cells.

PMID- 30227586
TI  - Re: Compartmentalized Activities of the Pyruvate Dehydrogenase Complex Sustain
      Lipogenesis in Prostate Cancer.

PMID- 30227587
TI  - Re: Short-Term Complications Associated with the Use of Transvaginal Mesh in
      Pelvic Floor Reconstructive Surgery: Results from a Multi-Institutional
      Prospectively Maintained Dataset.

PMID- 30227588
TI  - Re: Male Incontinence: The Etiology or Basis of Treatment.

PMID- 30227589
TI  - Re: Sacral Neuromodulation for Detrusor Hyperactivity with Impaired
      Contractility.

PMID- 30227590
TI  - Re: Effect of Uterosacral Ligament Suspension vs Sacrospinous Ligament Fixation
      with or without Perioperative Behavioral Therapy for Pelvic Organ Vaginal
      Prolapse on Surgical Outcomes and Prolapse Symptoms at 5 Years in the OPTIMAL
      Randomized Clinical Trial.

PMID- 30227591
TI  - Isolation of Novel Sesquiterpeniods and Anti-neuroinflammatory Metabolites from
      Nardostachys jatamansi.
AB  - Nardostachys jatamansi contains various types of sesquiterpenoids that may play
      an important role in the potency of plant's anti-inflammatory effects, depending
      on their structure. In this study, five new sesquiterpenoids, namely kanshone L
      (1), kanshone M (2), 7-methoxydesoxo-narchinol (3), kanshone N (4), and
      nardosdaucanol (5), were isolated along with four known terpenoids (kanshone D
      (6), nardosinanone G (7), narchinol A (8), and nardoaristolone B (9)) from the
      rhizomes and roots of Nardostachys jatamansi. Their structures were determined by
      analyzing 1D and 2D NMR and MS data. Among the nine sesquiterpenoids, compounds
      3, 4, and 8 were shown to possess dose-dependent inhibitory effects against
      lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV2
      microglial cells. Furthermore, compounds 3, 4, and 8 exhibited anti
      neuroinflammatory effects by inhibiting the production of pro-inflammatory
      mediators, including prostaglandin E2 (PGE2), inducible nitric oxide synthase
      (iNOS), and cyclooxygenase-2 (COX-2) proteins, as well as pro-inflammatory
      cytokines, such as interleukin (IL)-1beta, IL-12 and tumor necrosis factor-alpha
      (TNF-alpha), in LPS-stimulated BV2 microglial cells. Moreover, these compounds
      were shown to inhibit the activation of the NF-kappaB signaling pathway in LPS
      stimulated BV2 microglial cells by suppressing the phosphorylation of IkappaB
      alpha and blocking NF-kappaB translocation. In conclusion, five new and four
      known sesquiterpenoids were isolated from Nardostachys jatamansi, and compounds
      3, 4, and 8 exhibited anti-neuroinflammatory effects in LPS-stimulated BV2
      microglial cells through inhibiting of NF-kappaB signaling pathway.

PMID- 30227592
TI  - Total Synthesis of the Highly N-Methylated Peptides Carmabin A and Dragomabin.
AB  - The first total synthesis of carmabin A and dragomabin was achieved at 52.3 mg
      and 43.8 mg scale, respectively. The synthesis led to determination of the
      configuration of carmabin A and reassignment of the configuration of dragomabin
      at the stereogenic centre on the alkyne-bearing fragment.

PMID- 30227593
TI  - On the Use of Focused Incident Near-Field Beams in Microwave Imaging.
AB  - We consider the use of focused incident near-field (NF) beams to interrogate the
      object of interest (OI) in NF microwave imaging (MWI). To this end, we first
      discuss how focused NF beams can be advantageously utilized to suppress
      scattering effects from the neighbouring objects whose unknown dielectric
      properties are not of interest (i.e., undesired scatterers). We then discuss how
      this approach can also be helpful in reducing the required measured data points
      to perform imaging. Driven by the relation between the electromagnetic inverse
      source and inverse scattering problems, our approach emphasizes the importance of
      tailoring the induced contrast sources in the imaging domain through the utilized
      incident NF beams. To demonstrate this idea, we consider two recently-proposed NF
      beams, and simulate them for imaging applications. The first one is a
      subwavelength focused NF beam generated by a passive NF plate, and the other is a
      Bessel beam generated by a leaky radial waveguide. Simple imaging examples are
      considered to explore the potential advantages of this approach, in particular,
      toward mainly seeing the object of interest, and not the unknown undesired
      scatterers. The scope of this paper is limited to homogeneous dielectric objects
      for which the induced total field distributions in the interrogated objects are
      similar to the incident field distributions (e.g., those that satisfy the Born
      approximation). Simple inversion results for focused and non-focused beams are
      presented accompanied by discussions comparing the achieved reconstructed values.

PMID- 30227594
TI  - A National Survey of Community Pharmacists on Smoking Cessation Services in
      Thailand.
AB  - Providing smoking cessation services is one role of community pharmacists in
      Thailand. This cross-sectional study aimed to investigate activities and barriers
      related to smoking cessation services provided in community pharmacies in
      Thailand, as well as to compare these activities and barriers between those
      pharmacists providing and those not providing smoking cessation services. A
      postal questionnaire was conducted to collect information from community
      pharmacists across Thailand. In all, 413 valid responses were received from 5235
      questionnaires, giving a 7.9% response rate. Of the 413 respondents, 152 (37%)
      pharmacists provided smoking cessation services in their pharmacy. The activities
      of smoking cessation services varied. Time for counseling each smoker varied, a
      mean of 15.1 +/- 10.9 min (range 1-60) per person for the first time, and 8.9 +/-
      6.7 min (range 1-30) for each follow-up visit. Community pharmacists, providing
      smoking cessation services, were more likely to have pharmacist assistants, be a
      member of the Thai Pharmacy Network for Tobacco Control, and have more than 1
      pharmacist on duty. The most dispensed pharmaceutical product for smoking
      cessation was nicotine gum. Their most perceived barriers were being unable to
      follow-up and inadequate staff. In conclusion, only a minority of community
      pharmacists in Thailand are engaged in smoking cessation activities, even though
      some perceived barriers existed.

PMID- 30227595
TI  - Monitoring Nutrient Status of Brown Marmorated Stink Bug Adults and Nymphs on
      Summer Holly.
AB  - Halyomorpha halys (Stal), or brown marmorated stink bug (BMSB), has become a
      major pest and nuisance for both agricultural growers and homeowners since its
      arrival in North America and Europe. The nutritional ecology of BMSB is important
      for understanding its life history and rearing requirements. However, little is
      known about the nutritional status of wild populations, especially in the U.S.
      This research monitored the nutrient status of nymphal and adult BMSB collected
      from English holly in western Oregon. We measured their weight, nutrient index
      (weight/(prothorax * width)3), lipid, glycogen and sugar levels and egg load from
      May-September/October. First, glycogen and sugar levels of adults were often
      lowest sometime in June-August with a general increase by September. Meanwhile,
      their lipid levels varied without a discernible trend. Second, adult females had
      few eggs in May, with the highest egg load in June and July, and no eggs by
      September. Lastly, first and second nymphal instars were found in June, and
      fourth and fifth instars in September. Because nothing is known about the
      nutrient levels of nymphs, the reported values from this survey can assist future
      research on physiological responses of BMSB to treatments or environmental
      impacts in the field.

PMID- 30227596
TI  - Expression of the OAS Gene Family Is Highly Modulated in Subjects Affected by
      Juvenile Dermatomyositis, Resembling an Immune Response to a dsRNA Virus
      Infection.
AB  - BACKGROUND: Juvenile dermatomyositis (JDM) is a systemic, autoimmune, interferon
      (IFN)-mediated inflammatory muscle disorder that affects children younger than 18
      years of age. JDM primarily affects the skin and the skeletal muscles.
      Interestingly, the role of viral infections has been hypothesized. Mammalian 2'
      5'-oligoadenylate synthetase (OAS) genes have been thoroughly characterized as
      components of the IFN-induced antiviral system, and they are connected to several
      innate immune-activated diseases. The main purpose of the paper is to define the
      potential interrelationship between the OAS gene family network and the molecular
      events that characterize JDM along with double-stranded RNA (dsRNA) molecular
      pathways. METHODS: We analyzed three microarray datasets obtained from the NCBI
      in order to verify the expression levels of the OAS gene family network in muscle
      biopsies (MBx) of JDM patients compared to healthy controls. Furthermore, From
      GSE51392, we decided to select significant gene expression profiles of primary
      nasal and bronchial epithelial cells isolated from healthy subjects and treated
      with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of double
      stranded RNA (dsRNA), a molecular pattern associated with viral infection.
      RESULTS: The analysis showed that all OAS genes were modulated in JDM muscle
      biopsies. Furthermore, 99% of OASs gene family networks were significantly
      upregulated. Of importance, 39.9% of modulated genes in JDM overlapped with those
      of primary epithelial cells treated with poly(I:C). Moreover, the microarray
      analysis showed that the double-stranded dsRNA virus gene network was highly
      expressed. In addition, we showed that the innate/adaptive immunity markers were
      significantly expressed in JDM muscles biopsies. and that their levels were
      positively correlated to OAS gene family expression. CONCLUSION: OAS gene
      expression is extremely modulated in JDM as well as in the dsRNA viral gene
      network. These data lead us to speculate on the potential involvement of a viral
      infection as a trigger moment for this systemic autoimmune disease. Further in
      vitro and translational studies are needed to verify this hypothesis in order to
      strategically plan treatment interventions.

PMID- 30227597
TI  - Potato Spindle Tuber Viroid RNA-Templated Transcription: Factors and Regulation.
AB  - Viroids are circular noncoding RNAs that infect plants. Without encoding any
      protein, these noncoding RNAs contain the necessary genetic information for
      propagation in hosts. Nuclear-replicating viroids employ DNA-dependent RNA
      polymerase II (Pol II) for replication, a process that makes a DNA-dependent
      enzyme recognize RNA templates. Recently, a splicing variant of transcription
      factor IIIA (TFIIIA-7ZF) was identified as essential for Pol II to replicate
      potato spindle tuber viroid (PSTVd). The expression of TFIIIA-7ZF, particularly
      the splicing event, is regulated by a ribosomal protein (RPL5). PSTVd modulates
      its expression through a direct interaction with RPL5 resulting in optimized
      expression of TFIIIA-7ZF. This review summarizes the recent discoveries of host
      factors and regulatory mechanisms underlying PSTVd-templated transcription
      processes and raises new questions that may help future exploration in this
      direction. In addition, it briefly compares the machinery and the regulatory
      mechanism for PSTVd with the replication/transcription system of human hepatitis
      delta virus.

PMID- 30227598
TI  - The NS Segment of H1N1pdm09 Enhances H5N1 Pathogenicity in a Mouse Model of
      Influenza Virus Infections.
AB  - In 2009, the co-circulation of H5N1 and H1N1pdm09 raised concerns that a
      reassortment event may lead to highly pathogenic influenza strains. H1N1pdm09 and
      H5N1 are able to infect the same target cells of the lower respiratory tract. To
      investigate the capacity of the emergence of reassortant viruses, we
      characterized viruses obtained from the co-infection of cells with H5N1
      (A/Turkey/13/2006) and H1N1pdm09 (A/Lyon/969/2009 H1N1). In our analysis, all the
      screened reassortants possessed the PB2, HA, and NP segments from H5N1 and
      acquired one or two of the H1N1pdm09 segments. Moreover, the in vivo infections
      showed that the acquisition of the NS segment from H1N1pdm09 increased the
      virulence of H5N1 in mice. We conclude, therefore, that reassortment can occur
      between these two viruses, even if this process has never been detected in
      nature.

PMID- 30227599
TI  - Microbiological Changes during Ripening of Chihuahua Cheese Manufactured with Raw
      Milk and Its Seasonal Variations.
AB  - Chihuahua cheese is a traditional cheese produced in Northwest Mexico that is
      consumed shortly after production. Cheeses prepared during autumn, winter and
      summer were collected from five dairies, and analyzed to determine seasonal
      influence on proximate analysis, texture profile and the microbiological dynamic
      during a ripening period of 270 days. Coliforms, coagulase-positive
      staphylococci, molds, yeast, as well as presumptive mesophilic lactobacilli,
      thermophilic lactobacilli, lactococci, thermophilic cocci and enterococci, were
      enumerated by plate count on selective agar. Manufacturing dairy had an effect on
      Chihuahua cheese composition and texture profile. Seasonality influence on the
      microbial dynamic was observed, since the highest initial counts of coliforms
      (5.14 log CFU/g), coagulase-positive staphylococci (4.13 log CFU/g) and
      mesophilic lactobacilli (7.86 log CFU/g) were detected on summer samples. Also,
      ripening time affected the survival of coliforms and presumptive lactococci after
      270 days (1.24 and 5.89 log CFU/g respectively) while from day 90th, coagulase
      positive staphylococci were absent. Microbial changes and seasonal influence
      provide information on the microbiota that can influence the sensorial
      characteristics of Chihuahua cheese.

PMID- 30227600
TI  - Standards for Deriving Nonhuman Primate-Induced Pluripotent Stem Cells, Neural
      Stem Cells and Dopaminergic Lineage.
AB  - Humans and nonhuman primates (NHP) are similar in behavior and in physiology,
      specifically the structure, function, and complexity of the immune system. Thus,
      NHP models are desirable for pathophysiology and pharmacology/toxicology studies.
      Furthermore, NHP-derived induced pluripotent stem cells (iPSCs) may enable
      transformative developmental, translational, or evolutionary studies in a field
      of inquiry currently hampered by the limited availability of research specimens.
      NHP-iPSCs may address specific questions that can be studied back and forth
      between in vitro cellular assays and in vivo experimentations, an investigational
      process that in most cases cannot be performed on humans because of safety and
      ethical issues. The use of NHP model systems and cell specific in vitro models is
      evolving with iPSC-based three-dimensional (3D) cell culture systems and
      organoids, which may offer reliable in vitro models and reduce the number of
      animals used in experimental research. IPSCs have the potential to give rise to
      defined cell types of any organ of the body. However, standards for deriving
      defined and validated NHP iPSCs are missing. Standards for deriving high-quality
      iPSC cell lines promote rigorous and replicable scientific research and likewise,
      validated cell lines reduce variability and discrepancies in results between
      laboratories. We have derived and validated NHP iPSC lines by confirming their
      pluripotency and propensity to differentiate into all three germ layers
      (ectoderm, mesoderm, and endoderm) according to standards and measurable limits
      for a set of marker genes. The iPSC lines were characterized for their potential
      to generate neural stem cells and to differentiate into dopaminergic neurons.
      These iPSC lines are available to the scientific community. NHP-iPSCs fulfill a
      unique niche in comparative genomics to understand gene regulatory principles
      underlying emergence of human traits, in infectious disease pathogenesis, in
      vaccine development, and in immunological barriers in regenerative medicine.

PMID- 30227603
TI  - Biomolecular Clusters Distribution up to Mega Dalton Region Using MALDI
      Quadrupole Ion Trap Mass Spectrometer.
AB  - We present the first report on complete cluster distributions of cytochrome c
      (molecular weight of 12.4 kDa) and bovine serum albumin ((BSA), molecular weight
      of 66.4 kDa) with mass-to-charge ratio (m/z) reaching 350,000 and 1,400,000,
      respectively, by matrix-assisted laser desorption/ionization (MALDI). Large
      cluster distributions of the analytes were measured by our homemade frequency
      scanned quadrupole ion trap (QIT) mass spectrometer with a charge detector. To
      our knowledge, we report the highest m/z clusters of these two biomolecules. The
      quantitative results indicate that large clusters ions of cytochrome c and BSA
      follow the power law (r2 > 0.99) with cluster size distribution, which provides
      experimental evidence for the laser ablation studies of MALDI.

PMID- 30227602
TI  - The Effect of Gamification through a Virtual Reality on Preoperative Anxiety in
      Pediatric Patients Undergoing General Anesthesia: A Prospective, Randomized, and
      Controlled Trial.
AB  - The use of gamification in healthcare has been gaining popularity. This
      prospective, randomized, clinical trial was designed to evaluate whether
      gamification of the preoperative process-via virtual reality (VR) gaming that
      provides a vivid, immersive and realistic experience-could reduce preoperative
      anxiety in children. Seventy children scheduled for elective surgery under
      general anesthesia were randomly divided into either the control or gamification
      group. Children in the control group received conventional education regarding
      the preoperative process, whereas those in the gamification group played a 5 min
      VR game experiencing the preoperative experience. Preoperative anxiety, induction
      compliance checklist (ICC), and procedural behavior rating scale (PBRS) were
      measured. Sixty-nine children were included in the final analysis (control group
      = 35, gamification = 34). Preoperative anxiety (28.3 [23.3-36.7] vs. 46.7 [31.7
      51.7]; p < 0.001) and intraoperative compliance measured using ICC (p = 0.038)
      were lower in the gamification group than in the control group. However, PBRS (p
      = 0.092) and parent/guardian satisfaction (p = 0.268) were comparable between the
      two groups. VR experience of the preoperative process could reduce preoperative
      anxiety and improve compliance during anesthetic induction in children undergoing
      elective surgery and general anesthesia.

PMID- 30227604
TI  - Nanoparticles with High-Surface Negative-Charge Density Disturb the Metabolism of
      Low-Density Lipoprotein in Cells.
AB  - Endocytosis is an important pathway to regulate the metabolism of low-density
      lipoprotein (LDL) in cells. At the same time, engineering nanoparticles (ENPs)
      enter the cell through endocytosis in biomedical applications. Therefore, a
      crucial question is whether the nanoparticles involved in endocytosis could
      impact the natural metabolism of LDL in cells. In this study, we fabricated a
      series of gold nanoparticles (AuNPs) (13.00 +/- 0.69 nm) with varied surface
      charge densities. The internalized AuNPs with high-surface negative-charge
      densities (HSNCD) significantly reduced LDL uptake in HepG-2, HeLa, and SMMC-7721
      cells compared with those cells in control group. Notably, the significant
      reduction of LDL uptake in cells correlates with the reduction of LDL receptors
      (LDL-R) on the cell surface, but there is no change in protein and mRNA of LDL
      Rs. The cyclic utilization of LDL-R in cells is a crucial pathway to maintain the
      homoeostasis of LDL uptake. The release of LDL-Rs from LDL/LDL-R complexes in
      endosomes depended on reduction of the pH in the lumen. AuNPs with HSNCD hampered
      vacuolar-type H+-ATPase V1 (ATPaseV1) and ATPaseV0 binding on the endosome
      membrane, blocking protons to enter the endosome by the pump. Hence, fewer freed
      LDL-Rs were transported into recycling endosomes (REs) to be returned to cell
      surface for reuse, reducing the LDL uptake of cells by receptor-mediated
      endocytosis. The restrained LDL-Rs in the LDL/LDL-R complex were degraded in
      lysosomes.

PMID- 30227601
TI  - Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)
      beta in Physiological and Pathological Conditions.
AB  - Transforming growth factor (TGF)-beta is a multifunctional peptide growth factor
      that has a vital role in the regulation of cell growth, differentiation,
      inflammation, and repair in a variety of tissues, and its dysregulation mediates
      a number of pathological conditions including fibrotic disorders, chronic
      inflammation, cardiovascular diseases, and cancer progression. Regulation of TGF
      beta signaling is multifold, but one critical site of regulation is via
      interaction with certain extracellular matrix (ECM) microenvironments, as TGF
      beta is primarily secreted as a biologically inactive form sequestrated into ECM.
      Several ECM proteins are known to modulate TGF-beta signaling via cell-matrix
      interactions, including thrombospondins, SPARC (Secreted Protein Acidic and Rich
      in Cystein), tenascins, osteopontin, periostin, and fibulins. Fibulin family
      members consist of eight ECM glycoproteins characterized by a tandem array of
      calcium-binding epidermal growth factor-like modules and a common C-terminal
      domain. Fibulins not only participate in structural integrity of basement
      membrane and elastic fibers, but also serve as mediators for cellular processes
      and tissue remodeling as they are highly upregulated during embryonic development
      and certain disease processes, especially at the sites of epithelial-mesenchymal
      transition (EMT). Emerging studies have indicated a close relationship between
      fibulins and TGF-beta signaling, but each fibulin plays a different role in a
      context-dependent manner. In this review, regulatory interactions between
      fibulins and TGF-beta signaling are discussed. Understanding biological roles of
      fibulins in TGF-beta regulation may introduce new insights into the pathogenesis
      of some human diseases.

PMID- 30227606
TI  - Electrospinning of Ultrafine Conducting Polymer Composite Nanofibers with
      Diameter Less than 70 nm as High Sensitive Gas Sensor.
AB  - Polyvinyl alcohol/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)
      (PVA/PEDOT:PSS) composite ultrafine fibers were successfully fabricated by high
      pressure airflow assisted electrospinning. The electrical properties of
      PVA/PEDOT:PSS nanofibers with different diameters were characterized. The average
      diameter of the nanofibers can be down to 68 nm. Due to its large specific
      surface area, ammonia sensing of the ultrafine nanofibers is more sensitive than
      the traditional electrospun fibers (average fiber diameter of 263 nm). The
      ammonia sensing properties of the samples were tested by impedance analysis. The
      results show that ultrafine PVA/PEDOT:PSS nanofibers are more suitable for
      detecting low concentrations of ammonia with higher sensitivity.

PMID- 30227607
TI  - Relationship between Maternal and First Year of Life Dispensations of Antibiotics
      and Antiasthmatics.
AB  - Antibiotics are the most frequent prescription drugs used by pregnant women. Our
      objective was to investigate if the dispensation of antibiotics and
      antiasthmatics in children less than 1 year of age is associated with prenatal
      antibiotic exposure. A secondary aim was to explore the incidence of dispensed
      antibiotics in pregnancy and dispensed antibiotics and antiasthmatics in
      children. We conducted an observational study using the Peer Academic Detailing
      study database to select patients eligible for match in the Medical Birth
      Registry of Norway, a total of 7747 mother-and-child pairs. Details on antibiotic
      and antiasthmatic pharmacy dispensations were obtained from the Norwegian
      Prescription Database. One quarter (1948 of 7747) of the mothers in the study had
      been dispensed antibiotics during pregnancy. In their first year of life, 17%
      (1289) of the children had had an antibiotic dispensation, 23% (1747) an
      antiasthmatic dispensation, and 8% (619) of the children had had both. We found a
      significant association between dispensed antibiotics in pregnancy and dispensed
      antibiotics to the child during their first year of life; OR = 1.16 (95% CI:
      1.002-1.351). The association was stronger when the mothers were dispensed
      antibiotics at all, independent of the pregnancy period; OR = 1.60 (95% CI: 1.32
      1.94). We conclude that the probability for dispensation of antibiotics was
      increased in children when mothers were dispensed antibiotics, independent of
      pregnancy. Diagnostic challenges in the very young and parental doctor-seeking
      behavior may, at least in part, contribute to the association between
      dispensations in mothers and children below the age of one year.

PMID- 30227605
TI  - The Dual Role of MicroRNAs in Colorectal Cancer Progression.
AB  - Colorectal cancer (CRC) is responsible for one of the major cancer incidence and
      mortality worldwide. It is well known that MicroRNAs (miRNAs) play vital roles in
      maintaining the cell development and other physiological processes, as well as,
      the aberrant expression of numerous miRNAs involved in CRC progression. MiRNAs
      are a class of small, endogenous, non-coding, single-stranded RNAs that bind to
      the 3'-untranslated region (3'-UTR) complementary sequences of their target mRNA,
      resulting in mRNA degradation or inhibition of its translation as a post
      transcriptional regulators. Moreover, miRNAs also can target the long non-coding
      RNA (lncRNA) to regulate the expression of its target genes involved in
      proliferation and metastasis of CRC. The functions of these dysregulated miRNAs
      appear to be context specific, with evidence of having a dual role in both
      oncogenes and tumor suppression depending on the cellular environment in which
      they are expressed. Therefore, the unique expression profiles of miRNAs relate to
      the diagnosis, prognosis, and therapeutic outcome in CRC. In this review, we
      focused on several oncogenic and tumor-suppressive miRNAs specific to CRC, and
      assess their functions to uncover the molecular mechanisms of tumor initiation
      and progression in CRC. These data promised that miRNAs can be used as early
      detection biomarkers and potential therapeutic target in CRC patients.

PMID- 30227608
TI  - Factors Secreted by Cancer-Associated Fibroblasts that Sustain Cancer Stem
      Properties in Head and Neck Squamous Carcinoma Cells as Potential Therapeutic
      Targets.
AB  - This study investigates for the first time the crosstalk between stromal
      fibroblasts and cancer stem cell (CSC) biology in head and neck squamous cell
      carcinomas (HNSCC), with the ultimate goal of identifying effective therapeutic
      targets. The effects of conditioned media from cancer-associated fibroblasts
      (CAFs) and normal fibroblasts (NFs) on the CSC phenotype were assessed by
      combining functional and expression analyses in HNSCC-derived cell lines. Further
      characterization of CAFs and NFs secretomes by mass spectrometry was followed by
      pharmacologic target inhibition. We demonstrate that factors secreted by CAFs but
      not NFs, in the absence of serum/supplements, robustly increased anchorage
      independent growth, tumorsphere formation, and CSC-marker expression. Modulators
      of epidermal growth factor receptor (EGFR), insulin-like growth factor receptor
      (IGFR), and platelet-derived growth factor receptor (PDGFR) activity were
      identified as paracrine cytokines/factors differentially secreted between CAFs
      and NFs, in a mass spectrometry analysis. Furthermore, pharmacologic inhibition
      of EGFR, IGFR, and PDGFR significantly reduced CAF-induced tumorsphere formation
      and anchorage-independent growth suggesting a role of these receptor tyrosine
      kinases in sustaining the CSC phenotype. These findings provide novel insights
      into tumor stroma-CSC communication, and potential therapeutic targets to
      effectively block the CAF-enhanced CSC niche signaling circuit.

PMID- 30227609
TI  - Do Pentraxins Bind to Fungi in Invasive Human Gastrointestinal Candidiasis?
AB  - Tissue from 13 autopsy cases with invasive gastrointestinal candidiasis was
      studied for the binding of the pentraxins, C-reactive protein (CRP), pentraxin 3
      (PTX3), and serum amyloid P component (SAP) to fungal surfaces. Invasive candidal
      infection was demonstrated using a hematoxylin and eosin stain and a Gomori
      methenamine silver stain (GMS). Immunohistochemistry was performed with CRP and
      PTX3 monoclonal antibodies and did not demonstrate CRP or PTX3 bound to fungi (0
      of 13 cases), although CRP was extensively deposited on human tissue. A
      polyclonal antibody to SAP showed that SAP was bound to fungi in 12 of 13 cases.
      Although all three pentraxins have been reported to bind to fungi or bacteria,
      only SAP was bound to filamentous and yeast forms of Candida in human tissue, as
      detected by immunohistochemistry. SAP was abundantly present on fungi and may
      have affected the host innate immune response to the invading fungi.

PMID- 30227610
TI  - Effects of Marine n-3 Polyunsaturated Fatty Acids on Heart Rate Variability and
      Heart Rate in Patients on Chronic Dialysis: A Randomized Controlled Trial.
AB  - Marine n-3 polyunsaturated fatty acids (PUFA) may improve autonomic dysfunction,
      as indicated by an increase in heart rate variability (HRV) and reduce the risk
      of sudden cardiac death. Hence, the aim of this study was to investigate the
      effects of marine n-3 PUFA on 24-h HRV in patients on chronic dialysis, who have
      a high risk of sudden cardiac death. Between June 2014 and March 2016, 112
      patients on chronic dialysis from Denmark were allocated to a daily supplement of
      2 g marine n-3 PUFA or control for three months in a randomized, double-blinded,
      controlled trial. A 48-h Holter monitoring was performed and mean 24-h HRV
      indices for the two days were available in 85 patients. The mean age was 62.3
      years (SD: 14.3) and median dialysis vintage was 1.7 years (IQR: 0.5, 6.4).
      Within-group and between-group changes in outcome were evaluated by a paired and
      two sample t-test, respectively. Marine n-3 PUFA did not change the primary
      endpoint SDNN (SD of all RR-intervals) reflecting overall HRV, but other HRV
      indices increased and the mean RR-interval increased significantly, corresponding
      to a decrease in heart rate by 2.5 beats per minute (p = 0.04). In conclusion,
      marine n-3 PUFA did not change SDNN, but the mean heart rate was significantly
      reduced and changes in other HRV-indices were also observed, indicating an
      increase in vagal modulation that might be protective against malignant
      ventricular arrhythmias.

PMID- 30227611
TI  - The Development of Cytogenetic Maps for Malaria Mosquitoes.
AB  - Anopheline mosquitoes are important vectors of human malaria. Next-generation
      sequencing opens new opportunities for studies of mosquito genomes to uncover the
      genetic basis of a Plasmodium transmission. Physical mapping of genome sequences
      to polytene chromosomes significantly improves reference assemblies. High
      resolution cytogenetic maps are essential for anchoring genome sequences to
      chromosomes as well as for studying breakpoints of chromosome rearrangements and
      chromatin protein localization. Here we describe a detailed pipeline for the
      development of high-resolution cytogenetic maps using polytene chromosomes of
      malaria mosquitoes. We apply this workflow to the refinement of the cytogenetic
      map developed for Anopheles beklemishevi.

PMID- 30227612
TI  - Innovative Multi-Site Photoplethysmography Analysis for Quantifying Pulse
      Amplitude and Timing Variability Characteristics in Peripheral Arterial Disease.
AB  - Photoplethysmography (PPG) is a simple-to-perform vascular optics measurement
      technique that can detect blood volume changes in the microvascular bed of
      tissue. Beat-to-beat analysis of the PPG waveform enables the study of the
      variability of pulse features, such as the amplitude and the pulse arrival time
      (PAT), and when quantified in the time and frequency domains, has considerable
      potential to shed light on perfusion changes associated with peripheral arterial
      disease (PAD). In this pilot study, innovative multi-site bilateral finger and
      toe PPG recordings from 43 healthy control subjects and 31 PAD subjects were
      compared (recordings each at least five minutes, collected in a warm temperature
      controlled room). Beat-to-beat normalized amplitude variability and PAT
      variability were then quantified in the time-domain using two simple statistical
      measures and in the frequency-domain bilaterally using magnitude squared
      coherence (MSC). Significantly reduced normalized amplitude variability (healthy
      control 0.0384 (interquartile range 0.0217-0.0744) vs. PAD 0.0160 (0.0080-0.0338)
      (p < 0.0001)) and significantly increased PAT variability (healthy control 0.0063
      (0.0052-0.0086) vs. PAD 0.0093 (0.0078-0.0144) (p < 0.0001)) was demonstrated for
      the toe site in PAD using the time-domain analysis. Frequency-domain analysis
      demonstrated significantly lower MSC values across a range of frequency bands for
      PAD patients. These changes suggest a loss of right-to-left body side coherence
      and cardiovascular control in PAD. This study has also demonstrated the
      feasibility of using these measurement and analysis methods in studies
      investigating multi-site PPG variability for a wide range of cardiac and vascular
      patient groups.

PMID- 30227613
TI  - Prenylated Diphenyl Ethers from the Marine Algal-Derived Endophytic Fungus
      Aspergillus tennesseensis.
AB  - Considerable attention has been paid to marine derived endophytic fungi, owing to
      their capacity to produce novel secondary metabolites with potent bioactivities.
      In this study, two new compounds with a prenylated diphenyl ether structure
      diorcinol L (1) and (R)-diorcinol B (2)-were isolated from the marine algal
      derived endophytic fungus Aspergillus tennesseensis, along with seven known
      compounds: (S)-diorcinol B (3), 9-acetyldiorcinol B (4), diorcinol C (5),
      diorcinol D (6), diorcinol E (7), diorcinol J (8), and a dihydrobenzofuran
      derivative 9. Their structures were elucidated by extensive NMR spectroscopy
      studies. Compound 2 represents the first example of an R-configuration in the
      prenylated moiety. All these isolated compounds were examined for antimicrobial
      and cytotoxic activities. Compounds 1-9 exhibited antimicrobial activities
      against some human- and plant-pathogenic microbes with MIC values ranging from 2
      to 64 MUg/mL. Moreover, compound 9 displayed considerable inhibitory activity
      against the THP-1 cell line in vitro, with an IC50 value of 7.0 MUg/mL.

PMID- 30227614
TI  - Development of an Apparatus for Crop-Growth Monitoring and Diagnosis.
AB  - To non-destructively acquire leaf nitrogen content (LNC), leaf nitrogen
      accumulation (LNA), leaf area index (LAI), and leaf dry weight (LDW) data at high
      speed and low cost, a portable apparatus for crop-growth monitoring and diagnosis
      (CGMD) was developed according to the spectral monitoring mechanisms of crop
      growth. According to the canopy characteristics of crops and actual requirements
      of field operation environments, splitting light beams by using an optical filter
      and proper structural parameters were determined for the sensors. Meanwhile, an
      integral-type weak optoelectronic signal processing circuit was designed, which
      changed the gain of the system and guaranteed the high resolution of the
      apparatus by automatically adjusting the integration period based on the
      irradiance received from ambient light. In addition, a coupling processor system
      for a sensor information and growth model based on the microcontroller chip was
      developed. Field experiments showed that normalised vegetation index (NDVI)
      measured separately through the CGMD apparatus and the ASD spectrometer showed a
      good linear correlation. For measurements of canopy reflectance spectra of rice
      and wheat, their linear determination coefficients (R2) were 0.95 and 0.92,
      respectively while the root mean square errors (RMSEs) were 0.02 and 0.03,
      respectively. NDVI value measured by using the CGMD apparatus and growth indices
      of rice and wheat exhibited a linear relationship. For the monitoring models for
      LNC, LNA, LAI, and LDW of rice based on linear fitting of NDVI, R2 were 0.64,
      0.67, 0.63 and 0.70, and RMSEs were 0.31, 2.29, 1.15 and 0.05, respectively. In
      addition, R2 of the models for monitoring LNC, LNA, LAI, and LDW of wheat on the
      basis of linear fitting of NDVI were 0.82, 0.71, 0.72 and 0.70, and RMSEs were
      0.26, 2.30, 1.43, and 0.05, respectively.

PMID- 30227615
TI  - Finite Element Calculation with Experimental Verification for a Free-Flooded
      Transducer Based on Fluid Cavity Structure.
AB  - A free-flooded transducer that couples the vibration of a longitudinal vibration
      transducer and the fluid cavity of an aluminum ring was investigated. Given the
      transducer is based on a fluid cavity structure and has no air cavity, it can
      resist high hydrostatic pressure when working underwater, which is suitable for
      application in the deep sea. At first, the structure and working principle of the
      transducer were introduced. Then, the axisymmetric finite element model of the
      transducer was established; and the transmitting voltage response, admittance,
      and radiation directivity of the transducer were simulated using the finite
      element method. According to the size of the finite element model, a prototype of
      the transducer was designed and fabricated, and the electro-acoustic performance
      of the prototype was measured in an anechoic water tank. The experimental results
      were consistent with the simulation results and showed a good performance of the
      transducer. Finally, the improvement of the radiation directivity of the
      transducer by the optimal design of the free-flooded aluminum ring was obtained
      using the finite element method and verified by experiments.

PMID- 30227616
TI  - Tuberculosis among Full-Time Teachers in Southeast China, 2005-2016.
AB  - Objective: To explore the incidence rate and characteristics of tuberculosis (TB)
      among full-time teachers from 2005 to 2016 in southeast China and to provide a
      basis for TB prevention and control measures in schools. Methods: Information
      about full-time teachers with TB was obtained from the National Tuberculosis
      Information Management System (NTIMS). Population data were collected from the
      Zhejiang Statistical Yearbook and the Zhejiang Education Yearbook. The TB
      incidence rates and epidemiological characteristics of full-time teachers were
      analyzed and the Chi-square test was used to analyze influencing factors of
      epidemiological characteristics and clinical characteristics, case-finding delay,
      and treatment outcomes. Results: A total of 1795 teachers with TB were reported
      from 2005 to 2016, and the annual incidence rate was 28.87 per 100,000. The
      average annual PTB (pulmonary TB) incidence rate among full-time teachers was
      25.43/100,000 from 2005 to 2016 and the average annual PTB incidence rate among
      students was 15.40/100,000 from 2005 to 2016. The highest average incidence rates
      were observed in the QZ (Quzhou) and HZ (Hangzhou) districts. The male-to-female
      ratio of the patients was 0.95:1. Approximately half of the patients were 15-40
      years old. The mean case-finding interval was 45.3 days. Multivariable logistic
      regression analysis of TB case-finding delay among full-time teachers revealed
      that the older (OR = 1.44, 95% CI = 1.18-1.76, p < 0.01), not local (OR = 1.81,
      95% CI = 1.20-2.73, p < 0.01), retreatment (OR = 2.06, 95% CI = 1.39-3.08, p <
      0.01) and extra-pulmonary tuberculosis (OR = 1.71, 95% CI = 1.13-2.61, p = 0.01)
      cases were at high risk of case-finding delay. Compared to physical examination,
      patients detected by referrals and tracking (OR = 2.26, 95% CI = 1.16-4.38, p =
      0.02) and patients who directly visited the designated TB hospital (OR = 2.00,
      95% CI = 1.03-3.88, p = 0.04) were more prone to case-finding delay. The cure
      rate of full-time teachers with TB was 77.10%. The cure rates differed
      significantly between groups classified based on age, case-finding patterns,
      diagnostic results, treatment classifications, and strategies of patient
      management. Conclusion: The TB incidence rate among full-time teachers decreased
      from 2005 to 2016, but teachers suffered a higher risk of TB than students.
      Western Zhejiang was a hotspot for TB incidence among full-time teachers. Female
      teacher and young and middle-aged teacher cases account for the majority of the
      reported patients. There was a case-finding delay among full-time teachers with
      TB. We should conduct regular physical examinations and strengthen full-course
      supervision to reduce the risk of TB patients with case-finding delay and
      increase the TB cure rate.

PMID- 30227617
TI  - Optimization of Aminoimidazole Derivatives as Src Family Kinase Inhibitors.
AB  - Protein kinases have emerged as crucial targets for cancer therapy over the last
      decades. Since 2001, 40 and 39 kinase inhibitors have been approved by FDA and
      EMA, respectively, and the majority are antineoplastic drugs. Morevoer, many
      candidates are currently in clinical trials. We previously reported a small
      library of 4-aminoimidazole and 2-aminothiazole derivatives active as Src family
      kinase (SFK) inhibitors. Starting from these results, we decided to perform an
      optimization study applying a mix and match strategy to identify a more potent
      generation of 4-aminoimidazoles. Firstly, a computational study has been
      performed, then compounds showing the best predicted docking scores were
      synthesized and screened in a cell-free assay for their SFK inhibitory activity.
      All the new chemical entities showed IC50s in the nanomolar range, with 2-130
      fold increased activities compared to the previously reported inhibitors.
      Finally, the most active compounds have been tested on three cancer cell lines
      characterized by Src hyperactivation. Compounds 4k and 4l showed an interesting
      antiproliferative activity on SH-SY5Y neuroblastoma (NB) cell line. In this
      assay, the compounds resulted more potent than dasatinib, a tyrosine kinase
      inhibitor approved for the treatment of leukemias and in clinical trials for NB.

PMID- 30227618
TI  - RGB Colour Encoding Improvement for Three-Dimensional Shapes and Displacement
      Measurement Using the Integration of Fringe Projection and Digital Image
      Correlation.
AB  - Three-dimensional digital image correlation (3D-DIC) has become the most popular
      full-field optical technique for measuring 3D shapes and displacements in
      experimental mechanics. The integration of fringe projection (FP) and two
      dimensional digital image correlation (FP + DIC) has been recently established as
      an intelligent low-cost alternative to 3D-DIC, overcoming the drawbacks of a
      stereoscopic system. Its experimentation is based on the colour encoding of the
      characterized fringe and speckle patterns required for FP and DIC implementation,
      respectively. In the present work, innovations in experimentation using FP + DIC
      for more accurate results are presented. Specifically, they are based on the
      improvement of the colour pattern encoding. To achieve this, in this work, a
      multisensor camera and/or laser structural illumination were employed. Both
      alternatives are analysed and evaluated. Results show that improvements both in
      three-dimensional and in-plane displacement are obtained with the proposed
      alternatives. Nonetheless, multisensor high-speed cameras are uncommon, and laser
      structural illumination is established as an important improvement when low
      uncertainty is required for 2D-displacement measurement. Hence, the uncertainty
      has been demonstrated to be reduced by up to 50% compared with results obtained
      in previous experimental approaches of FP + DIC.

PMID- 30227619
TI  - In Vitro Activity of Newer and Conventional Antimicrobial Agents, Including
      Fosfomycin and Colistin, against Selected Gram-Negative Bacilli in Kuwait.
AB  - Limited data are available on susceptibilities of these organisms to some of the
      recently made accessible antimicrobial agents. The in vitro activities of newer
      antibiotics, such as, ceftolozane/tazobactam (C/T) and ceftazidime/avibactam
      (CZA) along with some "older" antibiotics, for example fosfomycin (FOS) and
      colistin (CL) were determined against selected strains (resistant to >= 3
      antimicrobial agents) of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas
      aeruginosa. Minimum inhibitory concentrations (MIC) were determined by Clinical
      and Laboratory Standards Institute microbroth dilution. 133 isolates: 46 E. coli,
      39 K. pneumoniae, and 48 P. aeruginosa were tested. Results showed that E. coli
      isolates with MIC50/90, 0.5/1 MU g / mL for CL; 4/32 MU g / mL for FOS; 0.25/32
      MU g / mL for C/T; 0.25/8 MU g / mL for CZA, exhibited susceptibility rates of
      95.7%, 97.8%, 76.1%, and 89.1%, respectively. On the other hand, K. pneumoniae
      strains with MIC50/90, 0.5/1 MU g / mL for CL; 256/512 MU g / mL for FOS; 2/128
      MU g / mL for C/T; 0.5/128 MU g / mL for CZA showed susceptibility rates of
      92.3%, 7.7%, 51.3%, and 64.1%, respectively. P. aeruginosa isolates with
      MIC50/90, 1/1 MU g / mL for CL; 128/128 MU g / mL for C/T; 32/64 MU g / mL for
      CZA presented susceptibility rates of 97.9%, 33.3%, and 39.6%, respectively.
      Higher MICs were demonstrated against most of the antibiotics. However, CL
      retained efficacy at low MICs against most of the isolates tested.

PMID- 30227621
TI  - Effect of Contact Pressure on the Performance of Carbon Nanotube Arrays Thermal
      Interface Material.
AB  - Vertically aligned carbon nanotube (CNT) arrays are promising candidates for
      advanced thermal interface materials (TIMs) since they possess high mechanical
      compliance and high intrinsic thermal conductivity. Some of the previous works
      indicate that the CNT arrays in direct dry contact with the target surface
      possess low contact thermal conductance, which is the dominant thermal
      resistance. Using a phase sensitive transient thermo-reflectance (PSTTR)
      technique, we measure the thermal conductance between CNT arrays and copper (Cu)
      surfaces under different pressures. The experiments demonstrated that the contact
      force is one of the crucial factors for optimizing the thermal performance of CNT
      array-based TIMs. The experimental results suggest that the Cu-CNT arrays'
      contact thermal conductance has a strong dependence on the surface deformation
      and has an order of magnitude rise as the contact pressure increases from 0.05 to
      0.15 MPa. However, further increase of the contact pressure beyond 0.15 MPa has
      little effect on the contact thermal resistance. This work could provide
      guidelines to determine the minimum requirement of packaging pressure on CNT
      TIMs.

PMID- 30227620
TI  - Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in
      Thyrocyte Physiology and Thyroid Disorders.
AB  - The key proteins responsible for hormone synthesis in the thyroid are
      glycosylated. Oligosaccharides strongly affect the function of glycosylated
      proteins. Both thyroid-stimulating hormone (TSH) secreted by the pituitary gland
      and TSH receptors on the surface of thyrocytes contain N-glycans, which are
      crucial to their proper activity. Thyroglobulin (Tg), the protein backbone for
      synthesis of thyroid hormones, is a heavily N-glycosylated protein, containing 20
      putative N-glycosylated sites. N-oligosaccharides play a role in Tg transport
      into the follicular lumen, where thyroid hormones are produced, and into
      thyrocytes, where hyposialylated Tg is degraded. N-glycans of the cell membrane
      transporters sodium/iodide symporter and pendrin are necessary for iodide
      transport. Some changes in glycosylation result in abnormal activity of the
      thyroid and alteration of the metabolic clearance rate of hormones. Alteration of
      glycan structures is a pathological process related to the progression of chronic
      diseases such as thyroid cancers and autoimmunity. Thyroid carcinogenesis is
      accompanied by changes in sialylation and fucosylation, beta1,6-branching of
      glycans, the content and structure of poly-LacNAc chains, as well as O
      GlcNAcylation, while in thyroid autoimmunity the main processes affected are
      sialylation and fucosylation. The glycobiology of the thyroid gland is an
      intensively studied field of research, providing new data helpful in
      understanding the role of the sugar component in thyroid protein biology and
      disorders.

PMID- 30227622
TI  - Sex-Mediated Differences in LPS Induced Alterations of TNFalpha, IL-10
      Expression, and Prostaglandin Synthesis in Primary Astrocytes.
AB  - Although many neurological and psychiatric disorders reveal clear sex-dependent
      variations, the molecular mechanism of this process is not clear enough.
      Astrocytes are involved in the response of neural tissue to injury and
      inflammation, produce steroid hormones, and sense steroid presence. To explore
      the hypothesis that astrocytes may participate in sex-mediated differences of
      inflammatory responses, we have examined whether male and female primary rat
      astrocytes show different responses to lipopolysaccharide (LPS) as a toll-like
      receptor 4 (TLR4) agonist. Levels of mRNA and proteins of tumor necrosis factor
      alpha (TNFalpha), interleukin-10 (IL-10), and cyclooxygenase (COX)-2 were
      assessed using qPCR, immunoblotting, and ELISA. UPLC-MS/MS was used to detect
      prostaglandins (PGs). LPS stimulation resulted in different levels of cytokine
      production; more TNFalpha and less IL-10 were produced in female cells compared
      with male astrocytes. Although the levels of the COX-2 expression were not
      altered, LPS significantly induced the synthesis of PGs with notable sex-related
      differences. PGE2 and PGD2 were less and 6-keto-PGF1alpha was more upregulated in
      female astrocytes, and TXB2 had similar levels in cells obtained from males and
      females. Trilostane, an inhibitor of 3beta-Hydroxysteroid dehydrogenase (3beta
      HSD), inhibited the LPS-induced TNFalpha production and the release of PGE2,
      PGD2, and 6-keto-PGF1alpha in female astrocytes. Thus, male and female astrocytes
      differentially respond to inflammatory challenges on the level of production of
      cytokines and steroid hormones. Sex-mediated differences in pro- and anti
      inflammatory responses should be taken into consideration for the effective
      treatment of disorders with neuroinflammation.

PMID- 30227623
TI  - RhoA/ROCK-2 Pathway Inhibition and Tight Junction Protein Upregulation by
      Catalpol Suppresses Lipopolysaccaride-Induced Disruption of Blood-Brain Barrier
      Permeability.
AB  - Lipopolysaccaride (LPS) directly or indirectly injures brain microvascular
      endothelial cells (BMECs) and damages the intercellular tight junction that gives
      rise to altered blood-brain barrier (BBB) permeability. Catalpol plays a
      protective role in LPS-induced injury, but whether catalpol protects against LPS
      caused damage of BBB permeability and the underlying mechanism remain to be
      delineated. Prophylactic protection with catalpol (5 mg/kg, i.v.) consecutively
      for three days reversed the LPS-induced damage of BBB by decreased Evans Blue
      (EB) leakage and restored tight junctions in C57 mice. Besides, catalpol co
      administrated with LPS increased BMECs survival, decreased their endothelin-1,
      TNF-Alpha and IL-6 secretion, improved transmembrane electrical resistance in a
      time-dependent manner, and in addition increased the fluorescein sodium
      permeability coefficient of BMECs. Also, transmission electron microscopy showed
      catalpol protective effects on tight junctions. Fluorescence staining displayed
      that catalpol reversed the rearrangement of the cytoskeleton protein F-actin and
      upregulated the tight junction protein of claudin-5 and ZO-1, which have been
      further demonstrated by the mRNA and protein expression levels of ZO-1, ZO-2, ZO
      3, claudin-5, and occludin. Moreover, catalpol concurrently downregulated the
      mRNA and protein levels of RhoA, and ROCK2, the critical proteins in the
      RhoA/ROCK2 signaling pathway. This study thus indicated that catalpol, via
      inhibition of the RhoA/ROCK2 signaling pathway, reverses the disaggregation of
      cytoskeleton actin in BMECs and prevents down-regulation of junctional proteins,
      such as claudin-5, occludin, and ZO-1, and decreases endothelin-1 and
      inflammatory cytokine secretion, eventually alleviating the increase in LPS
      induced BBB permeability.

PMID- 30227624
TI  - Sinomenine Protects Against Morphine Dependence through the NMDAR1/CAMKII/CREB
      Pathway: A Possible Role of Astrocyte-Derived Exosomes.
AB  - Sinomenine is a nonaddictive alkaloid used to prevent morphine dependence, even
      thoughits mechanism isnot fully understood. Astrocytes aggravate the pathological
      process in their neighboring cellsthrough exosomes in central nervous system
      diseases. However, the effect of sinomenine on astrocyte-derived exosomes for the
      amelioration of morphine dependence has not been reported yet. In this study, we
      found that sinomenine prevented the morphine-induced conditionedplace preference
      in mice. Sinomenine reduced the levels of cAMP and intracellular Ca2+ in morphine
      treated SH-SY5Y cells. Moreover, sinomenine inhibited the expressions of p
      NMDAR1/NMDAR1, p-CAMKII/CAMKII, and p-CREB/CREB in the hippocampusof morphine
      dependent mice and SH-SY5Y cells. Furthermore, we found that sinomenine
      inhibitedthe morphine-induced activation of astrocytesin vivo and in vitro.
      Afterwards, exosomes were isolated from cultured primary astrocytes treated with
      phosphate buffer saline (PBS, ctl-exo), morphine (mor-exo), or morphine and
      sinomenine (Sino-exo). Subsequently, morphine-treated SH-SY5Y cells were treated
      with ctl-exo, mor-exo, and Sino-exo. Results showed that Sino-exo reduced the
      level of cAMP, intracellular Ca2+, and the expression of p-CAMKII/CAMKII and p
      CREB/CREB in morphine-treated SH-SY5Y cells. In conclusion, we demonstrated that
      sinomenine exhibited protective effects against morphine dependencein vivo and in
      vitro through theNMDAR1/CAMKII/CREB pathway. Sinomenine-induced alterationof the
      function of astrocyte-derived exosomes may contribute to the antidependence
      effects of sinomenine in morphine dependence.

PMID- 30227625
TI  - Prunetin Relaxed Isolated Rat Aortic Rings by Blocking Calcium Channels.
AB  - Prunetin, a component of herbal medicines and various foods, such as pea, peach,
      cherry, and Prunus yedoensis, is a useful pharmacological compound. We previously
      reported the potent vasorelaxant effect of the bark of P. yedoensis. Therefore,
      we investigated the vasorelaxant activities of prunetin on isolated rat aortic
      rings and hypotensive activity on spontaneously hypertensive rats (SHR) in this
      study. In the present study, prunetin (1-30 MUg/mL) relaxed isolated rat aortic
      rings pre-contracted by phenylephrine (PE) in a concentration-dependent manner.
      Pre-incubation with prunetin (3 and 10 MUg/mL) inhibited vasoconstriction induced
      by the supply of Ca2+ in rat aortic rings pre-contracted with PE or KCl in a Ca2+
      free Krebs-Henseleit (KH) buffer. Prunetin (10 MUg/mL) pre-treatment also
      inhibited caffeine-induced contraction of aortic rings in a Ca2+-free KH buffer.
      To investigate the hypotensive effect of prunetin, the systolic blood pressure
      (SBP) of the SHR was measured by using a tail cuff assay. The SBP of SHR was
      significantly lower in the prunetin (25 mg/kg)-treated group. These results
      suggested that prunetin decreased blood pressure and relaxed blood vessels by
      blocking receptor-operated calcium channels, voltage-dependent calcium channels,
      and ryanodine receptor channels.

PMID- 30227626
TI  - Multi-Depot Open Vehicle Routing Problem with Time Windows Based on Carbon
      Trading.
AB  - In order to cut the costs of third-party logistics companies and respond to the
      Chinese government's low-carbon economy plans, this paper studies the more
      practical and complex open vehicle routing problem, which considers low-carbon
      trading policies. A low-carbon multi-depot open vehicle routing problem with time
      windows (MDOVRPTW) model is constructed with minimum total costs, which include
      the driver's salary, penalty costs, fuel costs and carbon emissions trading
      costs. Then, a two-phase algorithm is proposed to handle the model. In the first
      phase, the initial local solution is obtained with particle swarm optimization
      (PSO); in the second phase, we can obtain a global optimal solution through a
      further tabu search (TS). Experiments proved that the proposed algorithm is more
      suitable for small-scale cases. Furthermore, a series of experiments with
      different values of carbon prices and carbon quotas are conducted. The results of
      the study indicate that, as carbon trading prices and carbon quotas change, total
      costs, carbon emission trading costs and carbon emissions are affected
      accordingly. Based on these academic results, this paper presents some effective
      proposals for the government's carbon trading policy-making and also for
      logistics companies to have better route planning under carbon emission
      constraints.

PMID- 30227627
TI  - A Multiscale Analysis on the Superelasticity Behavior of Architected Shape Memory
      Alloy Materials.
AB  - In this paper, the superelasticity effects of architected shape memory alloys
      (SMAs) are focused on by using a multiscale approach. Firstly, a parametric
      analysis at the cellular level with a series of representative volume elements
      (RVEs) is carried out to predict the relations between the void fraction, the
      total stiffness, the hysteresis effect and the mass of the SMAs. The
      superelasticity effects of the architected SMAs are modeled by the
      thermomechanical constitutive model proposed by Chemisky et al. 2011. Secondly,
      the structural responses of the architected SMAs are studied by the multilevel
      finite element method (FE 2 ), which uses the effective constitutive behavior of
      the RVE to represent the behavior of the macroscopic structure. This approach can
      truly couple the responses of both the RVE level and structural level by the real
      time information interactions between two levels. Through a three point bending
      test, it is observed that the structure inherits the strong nonlinear responses
      both the hysteresis effect and the superelasticity-of the architected SMAs at the
      cellular level. Furthermore, the influence of the void fraction at the RVE level
      to the materials' structural responses can be more specifically and directly
      described, instead of using an RVE to predict at the microscopic level. Thus,
      this work could be referred to for optimizing the stiffness, the hysteresis
      effect and the mass of architected SMA structures and extended for possible
      advanced applications.

PMID- 30227628
TI  - Genome-Wide Association Studies of 39 Seed Yield-Related Traits in Sesame
      (Sesamum indicum L.).
AB  - Sesame is poised to become a major oilseed crop owing to its high oil quality and
      adaptation to various ecological areas. However, the seed yield of sesame is very
      low and the underlying genetic basis is still elusive. Here, we performed genome
      wide association studies of 39 seed yield-related traits categorized into five
      major trait groups, in three different environments, using 705 diverse lines.
      Extensive variation was observed for the traits with capsule size, capsule number
      and seed size-related traits, found to be highly correlated with seed yield
      indexes. In total, 646 loci were significantly associated with the 39 traits (p <
      10-7) and resolved to 547 quantitative trait loci QTLs. We identified six multi
      environment QTLs and 76 pleiotropic QTLs associated with two to five different
      traits. By analyzing the candidate genes for the assayed traits, we retrieved 48
      potential genes containing significant functional loci. Several homologs of these
      candidate genes in Arabidopsis are described to be involved in seed or biomass
      formation. However, we also identified novel candidate genes, such as SiLPT3 and
      SiACS8, which may control capsule length and capsule number traits. Altogether,
      we provided the highly-anticipated basis for research on genetics and functional
      genomics towards seed yield improvement in sesame.

PMID- 30227630
TI  - Design and Implementation of a Stereo Vision System on an Innovative 6DOF Single
      Edge Machining Device for Tool Tip Localization and Path Correction.
AB  - In the current meso cutting technology industry, the demand for more advanced,
      accurate and cheaper devices capable of creating a wide range surfaces and
      geometries is rising. To fulfill this demand, an alternative single point cutting
      device with 6 degrees of freedom (6DOF) was developed. Its main advantage
      compared to milling has been the need for simpler cutting tools that require an
      easier development. To obtain accurate and precise geometries, the tool tip must
      be monitored to compensate its position and make the proper corrections on the
      computer numerical control (CNC). For this, a stereo vision system was carried
      out as a different approach to the modern available technologies in the industry.
      In this paper, the artificial intelligence technologies required for implementing
      such vision system are explored and discussed. The vision system was compared
      with commercial measurement software Dino Capture, and a dedicated metrological
      microscope system TESA V-200GL. Experimental analysis were carried out and
      results were measured in terms of accuracy. The proposed vision system yielded an
      error equal to +/-3 um in the measurement.

PMID- 30227631
TI  - Layer by Layer Mesoporous Silica-Hyaluronic Acid-Cyclodextrin Bifunctional
      "Lamination": Study of the Application of Fluorescent Probe and Host-Guest
      Interactions in the Drug Delivery Field.
AB  - The layer-by-layer technique was exploited to adjust the magnitude of the host
      guest interactions between adamantane and cyclodextrin. The effect depends on
      numerous complex and changeable growth profiles of the films and the number of
      bilayers. These composite films of mesoporous silica nanoparticles and hyaluronic
      acid-cyclodextrin(HA-CD) were constructed to load the fluorescent dyes and
      peptides. The release rates of these molecules would decrease with an increase in
      the number of layers. A laser scanning confocal microscope was utilized to obtain
      the diffusion coefficient of fluorescein isothiocyanate. Hybrid films could be
      applied to increase the loading of different kinds of molecules and could also be
      integrated into the lamination to delay the rate of release.

PMID- 30227629
TI  - Immunogenic Effect of Hyperthermia on Enhancing Radiotherapeutic Efficacy.
AB  - Hyperthermia is a cancer treatment where tumor tissue is heated to around 40 
      degrees C. Hyperthermia shows both cancer cell cytotoxicity and immune response
      stimulation via immune cell activation. Immunogenic responses encompass the
      innate and adaptive immune systems, involving the activation of macrophages,
      natural killer cells, dendritic cells, and T cells. Moreover, hyperthermia is
      commonly used in combination with different treatment modalities, such as
      radiotherapy and chemotherapy, for better clinical outcomes. In this review, we
      will focus on hyperthermia-induced immunogenic effects and molecular events to
      improve radiotherapy efficacy. The beneficial potential of integrating
      radiotherapy with hyperthermia is also discussed.

PMID- 30227632
TI  - Developing a New Generation of Therapeutic Dental Polymers to Inhibit Oral
      Biofilms and Protect Teeth.
AB  - Polymeric tooth-colored restorations are increasingly popular in dentistry.
      However, restoration failures remain a major challenge, and more than 50% of all
      operative work was devoted to removing and replacing the failed restorations.
      This is a heavy burden, with the expense for restoring dental cavities in the
      U.S. exceeding $46 billion annually. In addition, the need is increasing
      dramatically as the population ages with increasing tooth retention in seniors.
      Traditional materials for cavity restorations are usually bioinert and replace
      the decayed tooth volumes. This article reviews cutting-edge research on the
      synthesis and evaluation of a new generation of bioactive dental polymers that
      not only restore the decayed tooth structures, but also have therapeutic
      functions. These materials include polymeric composites and bonding agents for
      tooth cavity restorations that inhibit saliva-based microcosm biofilms, bioactive
      resins for tooth root caries treatments, polymers that can suppress periodontal
      pathogens, and root canal sealers that can kill endodontic biofilms. These novel
      compositions substantially inhibit biofilm growth, greatly reduce acid production
      and polysaccharide synthesis of biofilms, and reduce biofilm colony-forming units
      by three to four orders of magnitude. This new class of bioactive and therapeutic
      polymeric materials is promising to inhibit tooth decay, suppress recurrent
      caries, control oral biofilms and acid production, protect the periodontium, and
      heal endodontic infections.

PMID- 30227633
TI  - CoII(Chromomycin)2 Complex Induces a Conformational Change of CCG Repeats from i
      Motif to Base-Extruded DNA Duplex.
AB  - We have reported the propensity of a DNA sequence containing CCG repeats to form
      a stable i-motif tetraplex structure in the absence of ligands. Here we show that
      an i-motif DNA sequence may transition to a base-extruded duplex structure with a
      GGCC tetranucleotide tract when bound to the (CoII)-mediated dimer of chromomycin
      A3, CoII(Chro)2. Biophysical experiments reveal that CCG trinucleotide repeats
      provide favorable binding sites for CoII(Chro)2. In addition, water hydration and
      divalent metal ion (CoII) interactions also play a crucial role in the
      stabilization of CCG trinucleotide repeats (TNRs). Our data furnish useful
      structural information for the design of novel therapeutic strategies to treat
      neurological diseases caused by repeat expansions.

PMID- 30227636
TI  - A Channel Phase Error Correction Method Based on Joint Quality Function of GF-3
      SAR Dual-Channel Images.
AB  - Multichannel SAR is an effective approach to solving the contradiction between
      high azimuth resolution and wide swath. The goal of this paper is to obtain a new
      and effective method for estimating and compensating the interchannel phase error
      of the Chinese GF-3 Synthetic aperture radar (SAR). A channel phase error
      correction method based on the optimal value of the image domain quality function
      is proposed. In this method, the phase error is initially compensated using the
      correlation function method. In the fine correction of dual-channel phase error,
      a heuristic search algorithm is used to estimate the residual phase by searching
      the extremum of the quality function. After phase compensation in the image
      domain, the azimuth ambiguities caused by the remaining phase are eliminated. The
      proposed image domain processing method provides a new idea for channel phase
      error correction. The measured data of high-resolution GF-3 dual-channel
      ultrafine imaging mode verifies the validity of this method.

PMID- 30227635
TI  - Dissociation of Fatty Liver and Insulin Resistance in I148M PNPLA3 Carriers:
      Differences in Diacylglycerol (DAG) FA18:1 Lipid Species as a Possible
      Explanation.
AB  - Fatty liver is tightly associated with insulin resistance and the development of
      type 2 diabetes. I148M variant in patatin-like phospholipase domain-containing
      protein 3 (PNPLA3) gene is associated with high liver fat but normal insulin
      sensitivity. The underlying mechanism of the disassociation between high liver
      fat but normal insulin sensitivity remains obscure. We investigated the effect of
      I148M variant on hepatic lipidome of subjects with or without fatty liver, using
      the Lipidyzer method. Liver samples of four groups of subjects consisting of
      normal liver fat with wild-type PNPLA3 allele (group 1); normal liver fat with
      variant PNPLA3 allele (group 2); high liver fat with wild-type PNPLA3 allele
      (group 3); high liver fat with variant PNPLA3 allele (group 4); were analyzed.
      When high liver fat to normal liver fat groups were compared, wild-type carriers
      (group 3 vs. group 1) showed similar lipid changes compared to I148M PNPLA3
      carriers (group 4 vs. group 2). On the other hand, in wild-type carriers,
      increased liver fat significantly elevated the proportion of specific DAGs
      (diacylglycerols), mostly DAG (FA18:1) which, however, remained unchanged in
      I148M PNPLA3 carriers. Since DAG (FA18:1) has been implicated in hepatic insulin
      resistance, the unaltered proportion of DAG (FA18:1) in I148M PNPLA3 carriers
      with fatty liver may explain the normal insulin sensitivity in these subjects.

PMID- 30227634
TI  - Rhizophagy Cycle: An Oxidative Process in Plants for Nutrient Extraction from
      Symbiotic Microbes.
AB  - In this paper, we describe a mechanism for the transfer of nutrients from
      symbiotic microbes (bacteria and fungi) to host plant roots that we term the
      'rhizophagy cycle.' In the rhizophagy cycle, microbes alternate between a root
      intracellular endophytic phase and a free-living soil phase. Microbes acquire
      soil nutrients in the free-living soil phase; nutrients are extracted through
      exposure to host-produced reactive oxygen in the intracellular endophytic phase.
      We conducted experiments on several seed-vectored microbes in several host
      species. We found that initially the symbiotic microbes grow on the rhizoplane in
      the exudate zone adjacent the root meristem. Microbes enter root tip meristem
      cells-locating within the periplasmic spaces between cell wall and plasma
      membrane. In the periplasmic spaces of root cells, microbes convert to wall-less
      protoplast forms. As root cells mature, microbes continue to be subjected to
      reactive oxygen (superoxide) produced by NADPH oxidases (NOX) on the root cell
      plasma membranes. Reactive oxygen degrades some of the intracellular microbes,
      also likely inducing electrolyte leakage from microbes-effectively extracting
      nutrients from microbes. Surviving bacteria in root epidermal cells trigger root
      hair elongation and as hairs elongate bacteria exit at the hair tips, reforming
      cell walls and cell shapes as microbes emerge into the rhizosphere where they may
      obtain additional nutrients. Precisely what nutrients are transferred through
      rhizophagy or how important this process is for nutrient acquisition is still
      unknown.

PMID- 30227637
TI  - The Association between Indoor Air Quality and Adult Blood Pressure Levels in a
      High-Income Setting.
AB  - Background: Indoor air pollution is still considered one of the leading causes of
      morbidity and mortality worldwide. We aimed to investigate the potential
      association between indoor particulate matter (PM) and fasting clinic blood
      pressure in adult Australians. Methods: Sixty-three participants residing within
      the Perth metropolitan area were studied. Participants were aged between 18 and
      65 years and free of major medical conditions. We conducted 24-h monitoring of
      residential PM concentrations, including the size fractions PM1, PM2.5, PM4, and
      PM10. All participants attended a clinical assessment at Curtin University
      following a 10-12 h overnight fast. Results: In this study we found that PM1 and
      PM2.5 were significantly associated with heart rate: a one interquartile range
      (IQR) increase in PM1 or PM2.5 was associated with a 4-6 beats per minute (bpm)
      increase in heart rate. Both PM10 and total PM exposure had a significant impact
      on systolic blood pressure (SBP): a one IQR increase in PM10 and total PM were
      associated with a 10 mmHg (95% CI: 0.77-20.05) and 12 mmHg (2.28-22.43 mmHg)
      increase in SBP, respectively. Conclusion: The study findings provide additional
      support to the thesis that indoor air pollution is an important modifiable factor
      in the risk of hypertension.

PMID- 30227638
TI  - Expression of Bioactive Lunasin Peptide in Transgenic Rice Grains for the
      Application in Functional Food.
AB  - Lunasin, a bioactive peptide initially isolated from soybean, has anticancer,
      anti-inflammatory, and antioxidant activity. Due its great application value,
      lunasin seems to be a candidate gene in improving the nutritional value of crops.
      In this study, lunasin was inserted into the rice genome to evaluate whether it
      was feasible to express lunasin using the rice expression system and improve the
      bioactivity of protein in rice for our needs. We generatedlunasin-overexpressing
      rice lines, and chose three independent transgenic rice lines for further study.
      The lunasin content in trans-lunasin rice detected by UPLC-MS/MS was 1.01 * 10-3
      g.kg-1 dry rice flour with grease removal in the lunasin extracts. The
      antioxidant efficacy of LET (lunasin-enriched fraction from trans-lunasin rice)
      and PEW (peptide-enriched fraction from wild type rice) was compared. Due to the
      presence of lunasin, LET showed higher (p < 0.05) antioxidant activity than PEW.
      LET exhibited high DPPH radical scavenging activity (IC50 value, 8 g.L-1), strong
      ABTS+ radical scavenging activity (IC50 value, 1.18 g.L-1), and great oxygen
      radical scavenging activity (170 MUmol.L-1 Trolox equivalents when the
      concentration reached 4 g.L-1). Moreover, LET presented significantly higher (p <
      0.05) anti-inflammatory activity on macrophage cells, and the NO production and
      the release of pro-inflammatory cytokines (IL-6, MCP1, and TNF-alpha) were
      significantly inhibited by LET. However, because of the low purity, LET showed
      weaker antioxidant and anti-inflammatory activity when compared to the Lunasin
      standard. These results suggested that it is feasible to use the rice expression
      system to express the exogenous lunasin in rice, and lunasin-overexpressing rice
      seems to be a candidate resource for application in functional food. Rice rich in
      lunasin is beneficial for human health, and could be used as a functional food in
      the diets of cancer and obese patients in the future.

PMID- 30227639
TI  - Analysis of Cuticular Lipids of the Pharaoh Ant (Monomorium pharaonis) and Their
      Selective Adsorption on Insecticidal Zeolite Powders.
AB  - The pharaoh ant is a notorious and hard to eradicate pest, which poses a threat
      in hospitals, spreading pathogens and contaminating sterile equipment. When
      applied on ants, zeolites adsorb part of their epicuticular wax layer. The ants
      are then vulnerable to desiccation, since this layer regulates water exchange. We
      analyzed the chemical composition of this wax layer using GC-MS (Gas
      Chromatography-Mass Spectrometry). A hexane wash of M. pharaonis foragers
      resulted in the identification of 53 components, four of which were not
      previously defined in Monomorium species. Selective adsorption of specific
      compounds on zeolites assisted in the identification of compounds which could not
      be separated on the GC column and allowed for the identification of three
      additional compounds. Zeolites show different affinities for the wax compounds
      depending on pore structure and chemical composition. Selective adsorption of
      alkanes on zeolites is also investigated in the fields of refinery processes and
      catalysis. Pore mouth and key lock adsorption mechanisms and selectivity
      according to molecular weight and branching, investigated in these fields, are
      also involved in adsorption processes of epicuticular waxes. The insecticidal
      activity of a zeolite is related to adsorption selectivity rather than capacity.
      One of the best adsorbing zeolites showed limited insecticidal activity and can
      be considered as a non-lethal alternative for epicuticular wax sampling.

PMID- 30227640
TI  - The Role of Next-Generation Sequencing in Precision Medicine: A Review of
      Outcomes in Oncology.
AB  - Precision medicine seeks to use genomic data to help provide the right treatment
      to the right patient at the right time. Next-generation sequencing technology
      allows for the rapid and accurate sequencing of many genes at once. This
      technology is becoming more common in oncology, though the clinical benefit of
      incorporating it into precision medicine strategies remains under significant
      debate. In this manuscript, we discuss the early findings of the impact of next
      generation sequencing on cancer patient outcomes. We investigate why not all
      patients with genomic variants linked to a specific therapy receive that therapy
      and describe current barriers. Finally, we explore the current state of health
      insurance coverage for individual genome sequencing and targeted therapies for
      cancer. Based on our analysis, we recommend increased transparency around the
      determination of "actionable mutations" and a heightened focus on investigating
      the variations in health insurance coverage across patients receiving sequencing
      matched therapies.

PMID- 30227642
TI  - Improving Sexual Health Education Programs for Adolescent Students through Game
      Based Learning and Gamification.
AB  - An effective innovative pedagogy for sexual health education is required to meet
      the demands of technology savvy digital natives. This study investigates the
      extent to which game-based learning (GBL) and gamification could improve the
      sexual health education of adolescent students. We conducted a randomized control
      trial of GBL and gamification experimental conditions. We made a comparison with
      traditional teaching as a control condition in order to establish differences
      between the three teaching conditions. The sexual health education topics were
      delivered in a masked fashion, 40-min a week for five weeks. A mixed-method
      research approach was uses to assess and analyze the results for 120 students
      from a secondary school in Dar Es Salaam, Tanzania. Students were divided into
      groups of 40 for each of the three teaching methods: GBL, gamification, and the
      control group (the traditional teaching method). The average post-test scores for
      GBL (Mean = 79.94, SD = 11.169) and gamification (Mean = 79.23, SD = 9.186) were
      significantly higher than the control group Mean = 51.93, SD = 18.705 (F (2, 117)
      = 54.75, p = 0.001). Overall, statistically significant differences (p <= 0.05)
      were found for the constructs of Motivation, Attitude, Knowledge, and Engagement
      (MAKE). This study suggests that the two innovative teaching approaches can be
      used to improve the sexual health education of adolescent students. The methods
      can potentially contribute socially, particularly in improving sexual health
      behaviour and adolescents' knowledge in regions plagued by years of sexual health
      problems, including HIV/AIDS.

PMID- 30227643
TI  - Regulation of Sphingolipid Metabolism by MicroRNAs: A Potential Approach to
      Alleviate Atherosclerosis.
AB  - The rapidly expanding field of bioactive lipids is exemplified by the many
      sphingolipids, which are structurally and functionally diverse molecules with
      significant physiologic functions. These sphingolipids are main constituents of
      cellular membranes and have been found associated with plasma lipoproteins, and
      their concentrations are altered in several metabolic disorders such as
      atherosclerosis, obesity, and diabetes. Understanding the mechanisms that
      regulate their biosynthesis and secretion may provide novel information that
      might be amenable to therapeutic targeting in the treatment of these diseases.
      Several sphingolipid synthesis genes have been targeted as potential therapeutics
      for atherosclerosis. In recent years, significant progress has been made in
      studying the role of microRNAs (miRNAs) in lipid metabolism. However, little
      effort has been made to investigate their role in sphingolipid metabolism.
      Sphingolipid biosynthetic pathways involve various enzymes that lead to the
      formation of several key molecules implicated in atherosclerosis, and the
      identification of miRNAs that regulate these enzymes could help us to understand
      these complex pathways better and may prove beneficial in alleviating
      atherosclerosis.

PMID- 30227641
TI  - Tracing Early Neurodevelopment in Schizophrenia with Induced Pluripotent Stem
      Cells.
AB  - Schizophrenia (SCZ) is a devastating mental disorder that is characterized by
      distortions in thinking, perception, emotion, language, sense of self, and
      behavior. Epidemiological evidence suggests that subtle perturbations in early
      neurodevelopment increase later susceptibility for disease, which typically
      manifests in adolescence to early adulthood. Early perturbations are thought to
      be significantly mediated through incompletely understood genetic risk factors.
      The advent of induced pluripotent stem cell (iPSC) technology allows for the in
      vitro analysis of disease-relevant neuronal cell types from the early stages of
      human brain development. Since iPSCs capture each donor's genotype, comparison
      between neuronal cells derived from healthy and diseased individuals can provide
      important insights into the molecular and cellular basis of SCZ. In this review,
      we discuss results from an increasing number of iPSC-based SCZ/control studies
      that highlight alterations in neuronal differentiation, maturation, and
      neurotransmission in addition to perturbed mitochondrial function and micro-RNA
      expression. In light of this remarkable progress, we consider also ongoing
      challenges from the field of iPSC-based disease modeling that call for further
      improvements on the generation and design of patient-specific iPSC studies to
      ultimately progress from basic studies on SCZ to tailored treatments.

PMID- 30227644
TI  - Synthesis and Antisense Properties of 2'beta-F-Arabinouridine Modified
      Oligonucleotides with 4'-C-OMe Substituent.
AB  - A novel 2'-F,4'-C-OMe-arabinouridine (araU) was successfully synthesized and
      introduced into oligonucleotides. The oligonucleotide containing 2'-F,4'-C-OMe
      araU exhibited improved nuclease resistance and RNA hybridizing selective ability
      relative to 2'-F-araU. In particular, when 2'-F,4'-C-OMe-araU inserted into C-H?F
      C bonding-favorable 5'-uridine-purine-3' steps, the modified oligonucleotide
      showed remarkable binding affinity and selectivity to RNA complements. Thus, 2'
      F,4'-C-OMe-araU has valuable antisense properties and can be used as novel
      chemical modification for antisense therapeutic strategy.

PMID- 30227645
TI  - Gut-Liver Axis: How Do Gut Bacteria Influence the Liver?
AB  - Chronic liver diseases are a major cause of morbidity and mortality worldwide.
      Recently, gut dysbiosis was identified as an important factor in the pathogenesis
      of liver diseases. The relationship between gut microbiota and the liver is still
      not well understood; however, dysfunction of the gut mucosal barrier ("leaky
      gut") and increased bacterial translocation into the liver via the gut-liver axis
      probably play crucial roles in liver disease development and progression. The
      liver is an important immunological organ, and, after exposure to gut-derived
      bacteria via portal circulation, it responds with activation of the innate and
      adaptive immune system, leading to hepatic injury. A better understanding of the
      pathophysiological links among gut dysbiosis, the integrity of the gut barrier,
      and the hepatic immune response to gut-derived factors is essential for the
      development of new therapies to treat chronic liver diseases.

PMID- 30227647
TI  - Cell Lineage Choice during Haematopoiesis: In Honour of Professor Antonius
      Rolink.

PMID- 30227646
TI  - Natural Product Chemistry of Gorgonian Corals of Genus Junceella-Part III.
AB  - The structures, names, bioactivities, and references of 82 natural products,
      including 48 new metabolites, purified from the gorgonian corals belonging to the
      genus Junceella are described in this review. All compounds mentioned in this
      review were obtained from Junceella fragilis, Junceella gemmacea, Junceella
      juncea, and Junceella sp., collected from tropical Indo-Pacific Ocean. Some of
      these compounds exhibited potential biomedical activities.

PMID- 30227649
TI  - Provider's Perceptions of Barriers and Facilitators for Latinas to Participate in
      Genetic Cancer Risk Assessment for Hereditary Breast and Ovarian Cancer.
AB  - The Comprehensive Cancer Network (NCCN) recommends genetic cancer risk assessment
      (GCRA) referral to women at high risk of hereditary breast and ovarian cancer.
      Latinas affected by breast cancer have the second highest prevalence of BRCA1/2
      mutations after Ashkenazi Jews. Compared to non-Hispanic Whites, Latinas have
      lower GCRA uptake. While some studies have identified barriers for GCRA use in
      this population, few studies have focused on health care providers' perspectives.
      The purpose of the study was to examine providers' perceptions of barriers and
      facilitators for at-risk Latina women to participate in GCRA and their
      experiences providing services to this population. We conducted semi-structured
      interviews with 20 healthcare providers (e.g., genetic counselors, patient
      navigators) recruited nationally through snowballing. Interviews were
      transcribed. Two coders independently coded each interview and then met to
      reconcile the codes using Consensual Qualitative Research guidelines. Providers
      identified several facilitators for GCRA uptake (e.g., family,
      treatment/prevention decisions) and barriers (e.g., cost, referrals, awareness,
      stigma). Genetic counselors described important aspects to consider when working
      with at-risk Latina including language barriers, obtaining accurate family
      histories, family communication, and testing relatives who live outside the US.
      Findings from this study can inform future interventions to enhance uptake and
      quality of GCRA in at-risk Latina women to reduce disparities.

PMID- 30227650
TI  - The Enhanced Lithium-Storage Performance for MnO Nanoparticles Anchored on
      Electrospun Nitrogen-Doped Carbon Fibers.
AB  - Manganese monoxide (MnO) is a promising anode material in the lithium-ion battery
      for its high capacity, low operation potential, and environmental benignity.
      However, its application is impeded by poor rate capability and rapid capacity
      fading. In this work, a MnO/carbon hybrid material, in which small-sized MnO
      nanoparticles are tightly anchored on carbon fibers (denoted as MnO@CFs), was
      prepared by annealing the electrospun precursor fibers at 650  degrees C. When
      applied as the anode material of the Li-ion battery, the small size of MnO
      shortens the Li-ion diffusion path, and the carbon fibers not only greatly
      improve the conductivity but also efficiently buffer the MnO structure strain
      during the charge-discharge process, endowing the MnO@CFs electrode with a good
      rate capability (185 mAh g-1 at 5 A g-1) and cyclic stability (406 mAh g-1 after
      500 cycles at 1.0 A g-1).

PMID- 30227651
TI  - A Blockchain Implementation Prototype for the Electronic Open Source Traceability
      of Wood along the Whole Supply Chain.
AB  - This is the first work to introduce the use of blockchain technology for the
      electronic traceability of wood from standing tree to final user. Infotracing
      integrates the information related to the product quality with those related to
      the traceability [physical and digital documents (Radio Frequency IDentification
      RFID-architecture)] within an online information system whose steps
      (transactions) can be made safe to evidence of alteration through the blockchain.
      This is a decentralized and distributed ledger that keeps records of digital
      transactions in such a way that makes them accessible and visible to multiple
      participants in a network while keeping them secure without the need of a
      centralized certification organism. This work implements a blockchain
      architecture within the wood chain electronic traceability. The infotracing
      system is based on RFID sensors and open source technology. The entire forest
      wood supply chain was simulated from standing trees to the final product passing
      through tree cutting and sawmill process. Different kinds of Internet of Things
      (IoT) open source devices and tags were used, and a specific app aiming the
      forest operations was engineered to collect and store in a centralized database
      information (e.g., species, date, position, dendrometric and commercial
      information).

PMID- 30227648
TI  - Novel Roles of Non-Coding RNAs in Opioid Signaling and Cardioprotection.
AB  - Cardiovascular disease (CVD) is a significant cause of morbidity and mortality
      across the world. A large proportion of CVD deaths are secondary to coronary
      artery disease (CAD) and myocardial infarction (MI). Even though prevention is
      the best strategy to reduce risk factors associated with MI, the use of
      cardioprotective interventions aimed at improving patient outcomes is of great
      interest. Opioid conditioning has been shown to be effective in reducing
      myocardial ischemia-reperfusion injury (IRI) and cardiomyocyte death. However,
      the molecular mechanisms behind these effects are under investigation and could
      provide the basis for the development of novel therapeutic approaches in the
      treatment of CVD. Non-coding RNAs (ncRNAs), which are functional RNA molecules
      that do not translate into proteins, are critical modulators of cardiac gene
      expression during heart development and disease. Moreover, ncRNAs such as
      microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are known to be induced by
      opioid receptor activation and regulate opioid signaling pathways. Recent
      advances in experimental and computational tools have accelerated the discovery
      and functional characterization of ncRNAs. In this study, we review the current
      understanding of the role of ncRNAs in opioid signaling and opioid-induced
      cardioprotection.

PMID- 30227652
TI  - Physician and Parental Decision-Making Prior to Acute Medical Paediatric
      Admission.
AB  - BACKGROUND: The number of acute medical paediatric emergency admissions is
      rising. We undertook qualitative interviews with parents and clinicians to better
      understand what factors, other than the health status of the child, may influence
      decision making leading to emergency admission. METHODS: Semi-structured
      interviews were conducted with parents; clinicians working in general practice,
      out-of-hours or the emergency department (referring clinicians); and doctors
      working in acute medical paediatrics (receiving clinicians). RESULTS: Ten
      parents, 7 referring clinicians and 10 receiving clinicians were interviewed.
      Parents described "erring on the side of caution" when seeking medical opinion
      and one mentioned anxiety. Among themes seen among referring clinicians, "erring
      on the side of caution" was also identified as was managing "parental anxiety"
      and acting on "gut instinct". Among receiving clinicians, themes included
      managing parental anxiety and increasing parental expectations of the health
      service. CONCLUSIONS: The study of parent and referring clinician decision-making
      prior to a hospital admission can identify "teachable moments" where
      interventions might be delivered to slow or even arrest the rise in short-stay
      acute medical admissions in Britain and other countries. Interventions could
      assure parents or referring clinicians that hospital referral is not required and
      help clinicians understand what they perceive as "parental anxiety".

PMID- 30227653
TI  - Combination of EGFR Inhibitor Lapatinib and MET Inhibitor Foretinib Inhibits
      Migration of Triple Negative Breast Cancer Cell Lines.
AB  - Triple-negative breast cancer (TNBC) is the most challenging subtype to treat due
      to the lack of estrogen receptor, progesterone receptor, and HER2 expression,
      which excludes the usage of directed targeted therapy against them. Promising
      therapeutic targets are the hepatocyte growth factor receptor (MET) and epidermal
      growth factor receptor (EGFR), which expression is frequently elevated in TNBC.
      Inhibitors of these receptors used as monotherapy are often ineffective. Due to
      that, we studied the efficacy of combined therapy targeting MET and EGFR
      simultaneously. Two TNBC cell lines were treated with lapatinib (a dual EGFR and
      HER2 inhibitor), foretinib (a MET inhibitor), or a combination of the two. After
      the inhibitors treatment, we verified the cell viability (XTT assay),
      distribution of the cell cycle phases, the activation of signaling pathways
      (Western blotting), distribution of invadopodia, fluorescent gelatin digestion
      (immunofluorescence), and the invasion capacity of cells. A combination of
      foretinib and lapatinib effectively reduced the viability of examined cells, led
      to G2/M arrest and reduction of pAKT. There was also a decreasein number of
      invadopodia formed by cells, their ability to digest gelatin and reduction of
      cells migration/invasion capacity. Therapy targeting of both EGFR and MET
      receptors was much more effective against tested cells than monotherapy. We
      selected a combination of drugs that could be successfully used against this
      breast cancer subtype.

PMID- 30227654
TI  - Preparation and Characterization of Magnesium Alloy Containing Al2Y Particles.
AB  - A magnesium alloy containing Al2Y particles was successfully fabricated by
      changing the content of Al in the Mg-6Y alloy melt. Its microstructure and
      mechanical properties were subsequently characterized. The results show that two
      types of Al2Y particles were discovered in the Mg-6Y-xAl (x = 0.5-5) alloys,
      which are namely the polygonal particles in the pre-precipitated phase and the
      discontinuous network of particles in the eutectic phase. With an increase in Al
      content, the amount of pre-precipitated Al2Y increases and the eutectic decreases
      gradually. When the Al content is 5 wt %, Al2Y particles are almost all in the
      pre-precipitated phase in the Mg-6Y alloy. After hot extrusion, the YA65 alloy
      could be regarded as the Mg master alloy that contains Al2Y particles with
      heterogeneous nucleation capability or Al2Y particle-reinforced magnesium matrix
      composites. The tensile strength of the as-extruded magnesium alloy is
      significantly improved at ambient temperatures.

PMID- 30227655
TI  - Integrated IMU with Faster R-CNN Aided Visual Measurements from IP Cameras for
      Indoor Positioning.
AB  - Considering the radio-based indoor positioning system pertaining to signal
      degradation due to the environmental factors, and rising popularity of IP
      (Internet Protocol) cameras in cities, a novel fusion of inertial measurement
      units (IMUs) with external IP cameras to determine the positions of moving users
      in indoor environments is presented. This approach uses a fine-tuned Faster R-CNN
      (Region Convolutional Neural Network) to detect users in images captured by
      cameras, and acquires visual measurements including ranges and angles of users
      with respect to the cameras based on the proposed monocular vision relatively
      measuring (MVRM) method. The results are determined by integrating the positions
      predicted by each user's inertial measurement unit (IMU) and visual measurements
      using an EKF (Extended Kalman Filter). The results experimentally show that the
      ranging accuracy is affected by both the detected bounding box's by Faster R-CNN
      height errors and diverse measuring distances, however, the heading accuracy is
      solely interfered with bounding box's horizontal biases. The indoor obstacles
      including stationary obstacles and a pedestrian in our tests more significantly
      decrease the accuracy of ranging than that of heading, and the effect of a
      pedestrian on the heading errors is greater than stationary obstacles on that. We
      implemented a positioning test for a single user and an external camera in five
      indoor scenarios to evaluate the performance. The robust fused IMU/MVRM solution
      significantly decreases the positioning errors and shows better performance in
      dense multipath scenarios compared with the pure MVRM solution and ultra-wideband
      (UWB) solution.

PMID- 30227657
TI  - Erratum: Xie, Z.-J.; Bao, X.-Y.; Peng, C.-F. Highly Sensitive and Selective
      Colorimetric Detection of Methylmercury Based on DNA-Functionalized Gold
      Nanoparticles. Sensors 2018, 18, 2679.
AB  - The authors wish to make the following corrections to their paper [...].

PMID- 30227658
TI  - Suicide Risk and Mental Disorders.

PMID- 30227656
TI  - Three-Dimensional Bioprinting of Cartilage by the Use of Stem Cells: A Strategy
      to Improve Regeneration.
AB  - Cartilage lesions fail to heal spontaneously, leading to the development of
      chronic conditions which worsen the life quality of patients. Three-dimensional
      scaffold-based bioprinting holds the potential of tissue regeneration through the
      creation of organized, living constructs via a "layer-by-layer" deposition of
      small units of biomaterials and cells. This technique displays important
      advantages to mimic natural cartilage over traditional methods by allowing a fine
      control of cell distribution, and the modulation of mechanical and chemical
      properties. This opens up a number of new perspectives including personalized
      medicine through the development of complex structures (the osteochondral
      compartment), different types of cartilage (hyaline, fibrous), and constructs
      according to a specific patient's needs. However, the choice of the ideal
      combination of biomaterials and cells for cartilage bioprinting is still a
      challenge. Stem cells may improve material mimicry ability thanks to their unique
      properties: the immune-privileged status and the paracrine activity. Here, we
      review the recent advances in cartilage three-dimensional, scaffold-based
      bioprinting using stem cells and identify future developments for clinical
      translation. Database search terms used to write this review were: "articular
      cartilage", "menisci", "3D bioprinting", "bioinks", "stem cells", and "cartilage
      tissue engineering".

PMID- 30227659
TI  - Tocotrienol-Rich Vitamin E from Palm Oil (Tocovid) and Its Effects in Diabetes
      and Diabetic Nephropathy: A Pilot Phase II Clinical Trial.
AB  - Tocotrienol-rich vitamin E from palm oil (Tocovid) has been shown to ameliorate
      diabetes through its superior antioxidant, antihyperglycemic, and anti
      inflammatory properties in diabetic rats. This study aimed to investigate the
      effects of Tocovid on diabetic nephropathy in patients with type 2 diabetes.
      Baseline parameters of potential subjects such as HbA1c, blood pressure, Advanced
      Glycation Endproduct (AGE), soluble receptor for AGE (sRAGE), Nepsilon
      Carboxymethyllysine (Nepsilon-CML), and Cystatin C were assessed for possible
      correlation with diabetic nephropathy. Only subjects with diabetic nephropathy or
      urine microalbuminuria-positive defined as Urine Albumin to Creatinine Ratio
      (UACR) >10 mg/mmol were recruited into a prospective, randomized, double-blinded,
      placebo-controlled trial. The intervention group (n = 22) received Tocovid 200 mg
      twice a day while the control group (n = 23) received placebo twice a day for 8
      weeks. Changes in Hemoglobin A1c (HbA1c), blood pressure, serum biomarkers and
      renal parameters such as UACR, serum creatinine, and estimated Glomerular
      Filtration Rate (eGFR) were compared between the two groups. It was found that
      serum Nepsilon-CML significantly correlated to the severity of microalbuminuria.
      For every 1 ng/mL increase in serum Nepsilon-CML, the odds of diabetic
      nephropathy increased by 1.476 times. Tocovid, compared to placebo, significantly
      reduced serum creatinine but not eGFR, UACR, HbA1c, blood pressure, and serum
      biomarkers. In conclusion, serum Nepsilon-CML is a potential biomarker for
      diabetic nephropathy. Treatment with Tocovid significantly reduced serum
      creatinine; therefore Tocovid may be a useful addition to the current treatment
      for diabetic nephropathy.

PMID- 30227660
TI  - The Oakville Oil Refinery Closure and Its Influence on Local Hospitalizations: A
      Natural Experiment on Sulfur Dioxide.
AB  - Background: An oil refinery in Oakville, Canada, closed over 2004-2005, providing
      an opportunity for a natural experiment to examine the effects on oil refinery
      related air pollution and residents' health. Methods: Environmental and health
      data were collected for the 16 years around the refinery closure. Toronto (2.5
      million persons) and the Greater Toronto Area (GTA, 6.3 million persons) were
      used as control and reference populations, respectively, for Oakville (160,000
      persons). We compared sulfur dioxide and age- and season-standardized
      hospitalizations, considering potential factors such as changes in demographics,
      socio-economics, drug prescriptions, and environmental variables. Results: The
      closure of the refinery eliminated 6000 tons/year of SO2 emissions, with an
      observed reduction of 20% in wind direction-adjusted ambient concentrations in
      Oakville. After accounting for trends, a decrease in cold-season peak-centered
      respiratory hospitalizations was observed for Oakville (reduction of 2.2
      cases/1000 persons per year, p = 0.0006 ) but not in Toronto (p = 0.856) and the
      GTA (p = 0.334). The reduction of respiratory hospitalizations in Oakville post
      closure appeared to have no observed link to known confounders or effect
      modifiers. Conclusion: The refinery closure allowed an assessment of the change
      in community health. This natural experiment provides evidence that a reduction
      in emissions was associated with improvements in population health. This study
      design addresses the impact of a removed source of air pollution.

PMID- 30227661
TI  - Effects of V and Co Element Addition on Microstructures and the Mechanical
      Properties of In Situ Biphasic Hybrid (TiCxNy-TiB2)/Ni Cermets.
AB  - In situ micro-(TiCxNy-TiB2)/Ni cermets with different Co and V content (2,5 and 8
      wt.%) were successfully fabricated by combustion synthesis and hot press
      consolidation in Ni-(V/Co)-Ti-B4C-BN systems. The results indicate that as Co
      content increased from 0 to 8 wt.%, the average sizes of the ceramic particles
      decreased, when the content of V increased from 0 to 8 wt.%, the size of the
      ceramic particles first decreased and then increased, and when the V content is
      5%, the ceramic particle size is the smallest. The Co element did not participate
      in the SHS reaction and was a diluent; therefore, when the Co element was added,
      the combustion temperature continued to decrease. When the V content was no more
      than 5 wt.%, as the V content increased, the maximum combustion temperature
      decreased. When the content of V was less than 5 wt.%, the concentration of V was
      not sufficient to greatly promote the generation of VN. Therefore, V absorbed a
      large amount of heat during the reaction, resulting in a continuous decrease in
      the reaction temperature of the reaction system during the reaction. When the
      content of the added V continued to increase to 8 wt.%, V participated in the
      reaction, which was exothermic. The results indicate that as Co content increased
      from 0 to 8 wt.%, the average sizes of the ceramic particles decreased, and the
      cermets with 5 wt.% Co possessed the best comprehensive properties: the highest
      hardness (1967 Hv), superior compression strength (3.25 GPa) and higher fracture
      strain (3.3%). Correspondingly, when the V content was 8 wt.%, the ultimate
      compressive strength and hardness of the cermets reached 1823 Hv and 3.11 GPa,
      respectively, 262 Hv and 0.17 GPa higher than those of the unalloyed cermets,
      respectively. Furthermore, the effects of Co and V on strengthening mechanisms
      were analyzed.

PMID- 30227662
TI  - Quantitative Cross-Platform Performance Comparison between Different Detection
      Mechanisms in Surface Plasmon Sensors for Voltage Sensing.
AB  - Surface plasmon Resonance (SPR) has recently been of interest for label-free
      voltage sensing. Several SPR structures have been proposed. However, making a
      quantitative cross-platform comparison for these structures is not
      straightforward due to (1) different SPR measurement mechanisms; (2) different
      electrolytic solution and concentration in the measurement; and (3) different
      levels of external applied potential. Here, we propose a quantitative approach to
      make a direct quantitative comparison across different SPR structures, different
      electrolytic solutions and different SPR measurement mechanisms. There are two
      structures employed as example in this theoretical study including uniform
      plasmonic gold sensor and bimetallic layered structure consisting of uniform
      silver layer (Ag) coated by uniform gold layer (Ag). The cross-platform
      comparison was carried by several performance parameters including sensitivity
      (S), full width half maximum (FWHM) and figure of merit (FoM). We also discuss
      how the SPR measurement mechanisms enhance the performance parameters and how the
      bimetallic layer can be employed to enhance the FoM by a factor of 1.34 to 25
      depending on the SPR detection mechanism.

PMID- 30227663
TI  - Targeted Neurotransmitters Profiling Identifies Metabolic Signatures in Rat Brain
      by LC-MS/MS: Application in Insomnia, Depression and Alzheimer's Disease.
AB  - Epidemiological, cross-sectional, and prospective studies have suggested that
      insomnia, Alzheimer's disease (AD) and depression are mutually interacting
      conditions and frequently co-occur. The monoamine and amino acid neurotransmitter
      systems in central nervous system were involved in the examination of
      neurobiological processes of this symptom complex. However, few studies have
      reported systematic and contrastive discussion of different neurotransmitters
      (NTs) changing in these neurological diseases. Thus, it is necessary to establish
      a reliable analytical method to monitoring NTs and their metabolite levels in rat
      brain tissues for elucidating the differences in pathophysiology of these
      neurological diseases. A rapid, sensitive and reliable LC-MS/MS method was
      established for simultaneous determination of the NTs and their metabolites,
      including tryptophan (Trp), tyrosine (Tyr), serotonin (5-HT), 5
      hydroxyindolacetic acid (5-HIAA), dopamine (DA), acetylcholine (ACh),
      norepinephrine (NE), glutamic acid (Glu), and gamma-aminobutyric acid (GABA) in
      rat brain tissues. The mobile phase consisting of methanol and 0.01% formic acid
      in water was performed on an Inertsil EP C18 column, and the developed method was
      validated well. Results demonstrated that there were significant differences for
      5-HT, DA, NE, Trp, Tyr and ACh between model and control group in all three
      models, and a Bayes linear discriminant function was established to distinguish
      these three kinds of nervous system diseases by DA, Tyr and ACh for their
      significant differences among control and three model groups. It could be an
      excellent strategy to provide perceptions into the similarity and differentia of
      mechanisms from the point of NTs' changing in brain directly and a new method to
      distinguish insomnia, depression and AD from view of essence.

PMID- 30227665
TI  - Road Transport of Farm Animals: Mortality, Morbidity, Species and Country of
      Origin at a Southern Italian Control Post.
AB  - Statistics on animal transport and its implications for health and welfare are
      limited. This study documented the animals transiting through a control post and
      their welfare outcomes measured by mortality rate and the prevalence of animals
      considered unfit for further transport (i.e., morbidity). Reports filed by the
      director of the control post and Official Veterinarians from 2010 to 2015 were
      analyzed. A total of 60,454 (54.2%) sheep/goats, 45,749 (41.0%) cattle, and 5333
      (4.8%) pigs travelled in 225 (16.2%), 1116 (80.2%) and 50 (3.6%) trucks,
      respectively. Trucks coming mainly from France (71.3%), Spain (14.0%), and
      Ireland (7.4%) went mainly to Greece (95.4%), which was also the most common
      nationality of the transport companies (44.6%). Cases of mortality and/or
      morbidity were reported for only 11 out of the 1391 trucks (0.8%). The average
      mortality and morbidity rates were 0.025% and 0.010%, with maximum values for
      transport of lambs (0.084%, and 0.019%). Species of animal being transported and
      space allowance were associated with the measured welfare outcomes (p < 0.05).
      Overall, this study provided statistics based on official surveillance reports,
      suggesting that small space allowance during long haul transportation of
      sheep/goats may affect their health and welfare.

PMID- 30227666
TI  - Associations between Bystanders and Perpetrators of Online Hate: The Moderating
      Role of Toxic Online Disinhibition.
AB  - Hatred directed at members of groups due to their origin, race, gender, religion,
      or sexual orientation is not new, but it has taken on a new dimension in the
      online world. To date, very little is known about online hate among adolescents.
      It is also unknown how online disinhibition might influence the association
      between being bystanders and being perpetrators of online hate. Thus, the present
      study focused on examining the associations among being bystanders of online
      hate, being perpetrators of online hate, and the moderating role of toxic online
      disinhibition in the relationship between being bystanders and perpetrators of
      online hate. In total, 1480 students aged between 12 and 17 years old were
      included in this study. Results revealed positive associations between being
      online hate bystanders and perpetrators, regardless of whether adolescents had or
      had not been victims of online hate themselves. The results also showed an
      association between toxic online disinhibition and online hate perpetration.
      Further, toxic online disinhibition moderated the relationship between being
      bystanders of online hate and being perpetrators of online hate. Implications for
      prevention programs and future research are discussed.

PMID- 30227667
TI  - Influence of Milling Parameters on Mechanical Properties of AA7075 Aluminum under
      Corrosion Conditions.
AB  - The paper describes an experimental study developed on the AA7075 T651, which is
      an aluminum alloy extensively used in the aeronautical industry. This work
      presents a double approach of investigation where there is no literature about
      previous research. This includes the analysis of the results obtained by the
      combination of mechanical and chemical actions on the mechanical properties of
      this material. On the one hand, the combinations of relevant milling parameters
      (feed rate, cutting speed) on flat samples (flat specimens have been selected by
      attempting to reproduce with the most accurate way the geometry and the type of
      machining process known as face milling is usually used in this manufacturing
      field). On the other hand, the stimulating effect of the corrosion by salt spray
      on selected batches of specimens was machined in the previous stage. Results from
      tensile tests performed on the whole of specimens allowed us to evaluate how the
      main mechanical properties (yield strength, tensile strength, and elongation at
      break) have been affected by the processes applied. Elongation at the break
      presents a reduction in an inverse order to feed a rate increase (up to 24.5%)
      and this reduction is extended (additional 19.17%) in specimens under corrosion
      conditions, which results in a greater fragility of the material.

PMID- 30227664
TI  - Selenite Reduction and the Biogenesis of Selenium Nanoparticles by
      Alcaligenesfaecalis Se03 Isolated from the Gut of Monochamus alternatus
      (Coleoptera: Cerambycidae).
AB  - In this study, a bacterial strain exhibiting high selenite (Na2SeO3) tolerance
      and reduction capacity was isolated from the gut of Monochamus alternatus larvae
      and identified as Alcaligenes faecalis Se03. The isolate exhibited extreme
      tolerance to selenite (up to 120 mM) when grown aerobically. In the liquid
      culture medium, it was capable of reducing nearly 100% of 1.0 and 5.0 mM Na2SeO3
      within 24 and 42 h, respectively, leading to the formation of selenium
      nanoparticles (SeNPs). Electron microscopy and energy dispersive X-ray analysis
      demonstrated that A. faecalis Se03 produced spherical electron-dense SeNPs with
      an average hydrodynamic diameter of 273.8 +/- 16.9 nm, localized mainly in the
      extracellular space. In vitro selenite reduction activity and real-time PCR
      indicated that proteins such as sulfite reductase and thioredoxin reductase
      present in the cytoplasm were likely to be involved in selenite reduction and the
      SeNPs synthesis process in the presence of NADPH or NADH as electron donors.
      Finally, using Fourier-transform infrared spectrometry, protein and lipid
      residues were detected on the surface of the biogenic SeNPs. Based on these
      observations, A. faecalis Se03 has the potential to be an eco-friendly candidate
      for the bioremediation of selenium-contaminated soil/water and a bacterial
      catalyst for the biogenesis of SeNPs.

PMID- 30227668
TI  - Macro-Encapsulation of Inorganic Phase-Change Materials (PCM) in Metal Capsules.
AB  - The design of phase-change material (PCM)-based thermal energy storage (TES)
      systems is challenging since a lot of PCMs have low thermal conductivities and a
      considerable volume change during phase-change. The low thermal conductivity
      restricts energy transport due to the increasing thermal resistance of the
      progressing phase boundary and hence large heat transfer areas or temperature
      differences are required to achieve sufficient storage power. An additional
      volume has to be considered in the storage system to compensate for volume
      change. Macro-encapsulation of the PCM is one method to overcome these drawbacks.
      When designed as stiff containers with an air cushion, the macro-capsules
      compensate for volume change of the PCM which facilitates the design of PCM
      storage systems. The capsule walls provide a large surface for heat transfer and
      the thermal resistance is reduced due to the limited thickness of the capsules.
      Although the principles and advantages of macro-encapsulation have been well
      known for many years, no detailed analysis of the whole encapsulation process has
      been published yet. Therefore, this research proposes a detailed development
      strategy for the whole encapsulation process. Various possibilities for corrosion
      protection, fill and seal strategies and capsule geometries are studied. The
      proposed workflow is applied for the encapsulation of the salt hydrate
      magnesiumchloride hexahydrate (MCHH, MgCl 2 . 6 H 2 O) within metal capsules but
      can also be assigned to other material combinations.

PMID- 30227670
TI  - Structured Background Modeling for Hyperspectral Anomaly Detection.
AB  - Background modeling has been proven to be a promising method of hyperspectral
      anomaly detection. However, due to the cluttered imaging scene, modeling the
      background of an hyperspectral image (HSI) is often challenging. To mitigate this
      problem, we propose a novel structured background modeling-based hyperspectral
      anomaly detection method, which clearly improves the detection accuracy through
      exploiting the block-diagonal structure of the background. Specifically, to
      conveniently model the multi-mode characteristics of background, we divide the
      full-band patches in an HSI into different background clusters according to their
      spatial-spectral features. A spatial-spectral background dictionary is then
      learned for each cluster with a principal component analysis (PCA) learning
      scheme. When being represented onto those dictionaries, the background often
      exhibits a block-diagonal structure, while the anomalous target shows a sparse
      structure. In light of such an observation, we develop a low-rank representation
      based anomaly detection framework that can appropriately separate the sparse
      anomaly from the block-diagonal background. To optimize this framework
      effectively, we adopt the standard alternating direction method of multipliers
      (ADMM) algorithm. With extensive experiments on both synthetic and real-world
      datasets, the proposed method achieves an obvious improvement in detection
      accuracy, compared with several state-of-the-art hyperspectral anomaly detection
      methods.

PMID- 30227669
TI  - Characterization of Cultivar Differences of Blueberry Wines Using GC-QTOF-MS and
      Metabolic Profiling Methods.
AB  - A non-targeted volatile metabolomic approach based on the gas chromatography
      quadrupole time of fight-mass spectrometry (GC-QTOF-MS) coupled with two
      different sample extraction techniques (solid phase extraction and solid phase
      microextraction) was developed. Combined mass spectra of blueberry wine samples,
      which originated from two different cultivars, were subjected to orthogonal
      partial least squares-discriminant analysis (OPLS-DA). Principal component
      analysis (PCA) reveals an excellent separation and OPLS-DA highlight metabolic
      features responsible for the separation. Metabolic features responsible for the
      observed separation were tentatively assigned to phenylethyl alcohol, cinnamyl
      alcohol, benzenepropanol, 3-hydroxy-benzenethanol, methyl eugenol, methyl
      isoeugenol, (E)-asarone, (Z)-asarone, and terpenes. Several of the selected
      markers enabled a distinction in secondary metabolism to be drawn between two
      blueberry cultivars. It highlights the metabolomic approaches to find out the
      influence of blueberry cultivar on a volatile composition in a complex blueberry
      wine matrix. The distinction in secondary metabolism indicated a possible O
      methyltransferases activity difference among the two cultivars.

PMID- 30227672
TI  - An Advanced, Silicon-Based Substrate for Sensitive Nucleic Acids Detection.
AB  - Surface substrate and chemical functionalization are crucial aspects for the
      fabrication of the sensitive biosensor based on microarray technology. In this
      paper, an advanced, silicon-based substrate (A-MA) allowing enhancement of
      optical signal for microarray application is described. The substrate consists in
      a multilayer of Si/Al/SiO2 layers. The optical signal enhancement is reached by a
      combination of the mirror effect of Al film and the SiO2 thickness around 830 nm,
      which is able to reach the maximum of interference for the emission wavelength of
      the Cy5 fluorescent label. Moreover, SiO2 layer is suitable for the
      immobilization of single-strand DNA through standard silane chemistry, and probe
      densities of about 2000 F/um2 are reached. The microarray is investigated in the
      detection of HBV (Hepatitis B Virus) pathogen with analytical samples, resulting
      in a dynamic linear range of 0.05-0.5 nM, a sensitivity of about 18000 a.u. nM-1,
      and a Limit of Detection in the range of 0.031-0.043 Nm as a function of the
      capture probe sequence.

PMID- 30227671
TI  - Electrospinning Fabrication of Poly(vinyl alcohol)/Coptis chinensis Extract
      Nanofibers for Antimicrobial Exploits.
AB  - Coptis chinensis (CC) is used in conventional Chinese medicine. The main active
      components of CC are isoquinoline alkaloids, including berberine, coptisine,
      palmatine, and magnoflorine; all these are known to have several pharmacological
      properties. Poly(vinyl alcohol) (PVA) is a well-known synthetic biocompatible
      polymer suitable for a range of pharmaceutical uses; it can be used as a matrix
      for the incorporation of functional materials and has a wide range of
      applications in the cosmetics, food, pharmaceutical, and packaging industries. In
      this study, PVA-based electrospun nanofibers containing CC extract were
      successfully fabricated. Furthermore, the effects of different CC extract
      contents on the morphologies, and antimicrobial and antifungal properties of
      PVA/CC extract nanofibers were investigated. Morphological changes were observed
      using different molecular weights of PVA. For characterization, field-emission
      scanning electron microscopy, thermogravimetric analysis, and Fourier transform
      infrared analysis were performed. The effectiveness of these nanofibers has been
      demonstrated by evaluating the thermal stability against Staphylococcus aureus,
      antimicrobial activity against Staphylococcus aureus and Staphylococcus
      epidermidis, and the antifungal activity against the fungi Aureobasidium
      pullulans and Penicillium pinophilum. The PVA/CC extract nanofibers were found to
      have excellent antibacterial and antifungal activity and thermal stability;
      hence, their use in medicinal sectors is highly recommended.

PMID- 30227673
TI  - Permeability Behavior of Nanocrystalline Solid Dispersion of Dipyridamole
      Generated Using NanoCrySP Technology.
AB  - Nanocrystals research has been an area of significant interest lately, providing
      oral bioavailability benefits to solubility- and/or dissolution rate-limited
      drugs. Drug nanocrystals are generated using top-down or bottom-up technologies.
      Combination technologies (Nanoedge, Nanopure XP and SmartCrystal) have been
      recently developed to generate nanocrystals of improved properties. Our lab has
      also contributed in this field by providing a 'novel' platform technology,
      NanoCrySP, for the generation of nanocrystals. NanoCrySP-generated nanocrystals
      have improved the oral bioavailability of various molecules. In this study, we
      aim to assess the permeability behavior of nanocrystals generated by NanoCrySP.
      Three samples of Dipyridamole (DPM) drug were used in this study: (1) DPM (micron
      sized powder), (2) nanocrystals of DPM (NS), generated by media milling (as
      control) and, (3) nanocrystalline solid dispersion containing DPM (NSD) in the
      matrix of mannitol (MAN), generated using NanoCrySP technology. In vitro (Caco-2
      cell lines) and ex vivo (everted gut sac) studies were conducted in this work.
      Cellular permeability (Papp) from apical-to-basolateral side in Caco-2 cell
      monolayer was found to be in the order NS > NSD > DPM, which was the same as
      their apparent solubility values. Higher Papp from a basolateral-to-apical side
      suggested a significant contribution of the P-gp efflux transport for DPM, while
      NS exhibited much higher inhibition of the efflux mechanism than NSD. Both NS and
      NSD showed higher permeation from the jejunum region in the ex vivo everted gut
      sac study. Interestingly, Papp of NSD was similar to NS in ex vivo everted gut
      sac model, however, NSD showed higher mucoadhesion than NS and DPM in this study.

PMID- 30227674
TI  - Pre-Procedural Statin Use Is Associated with Improved Long-Term Survival and
      Reduced Major Cardiovascular Events in Patients Undergoing Carotid Artery
      Stenting: A Retrospective Study.
AB  - Carotid artery stenting (CAS) is a minimal invasive procedure used to resolve
      carotid occlusion that can be affected by peri-procedural complications. Statin
      use before CAS has shown to reduce peri-procedural risk and improve survival,
      though time-dependent cofactors that influence mortality has not been considered.
      The aim of this study was to evaluate long-term survival of patients who undergo
      CAS considering new occurred major adverse cardiovascular event (MACE) as time
      dependent cofactor. In this study, 171 high cardiovascular risk patients (age 72
      +/- 8 years, 125 males) were enrolled after CAS procedure and were followed for a
      median of 8.4 years. Death occurred in 44% of patients with a mean time to death
      of 69 +/- 39 months and MACE in 34% with a mean time of 35 +/- 42 months. In
      patients who used or not statins at baseline, death occurred in 33% and 65%,
      respectively (p < 0.001). Survival analysis showed that statin use reduced risk
      of death (hazard ratio HR 0.36, 95% confidence interval CI 0.23-0.58, p <
      0.0001). Including MACE as time-dependent variable did not change beneficial
      effects of statins. Additionally, statin use was associated with a protective
      effect on MACE (HR 0.48, 95% CI 0.27-0.85, p = 0.012); particularly, the
      prevalence of stroke was reduced by 59% (p = 0.018). In multivariate analysis,
      effects of statins were independent of demographic and anthropometric variables,
      prevalence of cardiovascular risk factors, renal function, antiplatelet use, and
      MACE occurrence. In conclusion, use of statins before CAS procedure is associated
      with increased long-term survival and reduced MACE occurrence. This evidence
      supports the hypothesis that statin use before CAS might be beneficial in high
      risk patients.

PMID- 30227675
TI  - Effects of Statin Use in Advanced Chronic Kidney Disease Patients.
AB  - Although statin treatment is recommended for patients with chronic kidney disease
      (CKD) stages I-IV, its potential benefits have not been reported in advanced CKD
      patients. Non-diabetic patients with advanced CKD (pre-dialysis patients,
      estimated glomerular filtration rate <15 mL/min/1.73 m2) were enrolled from a
      National Health Insurance Research Database with a population of 23 million.
      Statin users and non-users were matched using propensity scoring and analyzed
      using Cox proportional hazards models, taking mortality as a competing risk with
      subsequent end-stage renal disease (ESRD) and statin doses as time-dependent
      variables. A total of 2551 statin users and 7653 matched statin non-users were
      identified from a total 14,452 patients with advanced CKD. Taking mortality as a
      competing risk, statin use did not increase the risk of new-onset diabetes
      mellitus (NODM) or decrease the risk of de novo major adverse cardiovascular
      events (MACE), but reduced all-cause mortality (hazard ratio (HR) = 0.59 [95% CI
      0.42-0.84], p = 0.004) and sepsis-related mortality (HR = 0.53 [95% CI 0.32
      0.87], p = 0.012). For advanced CKD patients, statin was neither associated with
      increased risks of developing NODM, nor with decreased risk of de novo MACE
      occurrence, but with a reduced risk of all-cause mortality, mainly septic deaths.

PMID- 30227676
TI  - Analysis of bZIP Transcription Factor Family and Their Expressions under Salt
      Stress in Chlamydomonas reinhardtii.
AB  - The basic leucine-region zipper (bZIP) transcription factors (TFs) act as crucial
      regulators in various biological processes and stress responses in plants.
      Currently, bZIP family members and their functions remain elusive in the green
      unicellular algae Chlamydomonas reinhardtii, an important model organism for
      molecular investigation with genetic engineering aimed at increasing lipid yields
      for better biodiesel production. In this study, a total of 17 C. reinhardtii bZIP
      (CrebZIP) TFs containing typical bZIP structure were identified by a genome-wide
      analysis. Analysis of the CrebZIP protein physicochemical properties,
      phylogenetic tree, conserved domain, and secondary structure were conducted.
      CrebZIP gene structures and their chromosomal assignment were also analyzed.
      Physiological and photosynthetic characteristics of C. reinhardtii under salt
      stress were exhibited as lower cell growth and weaker photosynthesis, but
      increased lipid accumulation. Meanwhile, the expression profiles of six CrebZIP
      genes were induced to change significantly during salt stress, indicating that
      certain CrebZIPs may play important roles in mediating photosynthesis and lipid
      accumulation of microalgae in response to stresses. The present work provided a
      valuable foundation for functional dissection of CrebZIPs, benefiting the
      development of better strategies to engineer the regulatory network in microalgae
      for enhancing biofuel and biomass production.

PMID- 30227677
TI  - Prevalence and Predictors of Malaria in Human Immunodeficiency Virus Infected
      Patients in Beira, Mozambique.
AB  - Co-infection between malaria and HIV has major public health implications. The
      aims of this study were to assess the malaria prevalence and to identify
      predictors of positivity to malaria Test in HIV positive patients admitted to the
      health center Sao Lucas of Beira, Mozambique. A retrospective cross-sectional
      study was performed from January 2016 to December 2016. Overall, 701 adult HIV
      patients were enrolled, positivity to malaria test was found in 232 (33.0%).
      These patients were found to be more frequently unemployed (76.3%), aged under 40
      (72.0%), with a HIV positive partner (22.4%) and with a CD4 cell count <200
      (59.9%). The following variables were predictors of malaria: age under 40 (O.R. =
      1.56; 95%CI: 1.22-2.08), being unemployed (O.R. = 1.74; 95%CI: 1.24-2.21),
      irregularity of cotrimoxazole prophylaxis's (O.R. = 1.42; 95%CI: 1.10-1.78), CD4
      cell count <200 (O.R. = 2.01; 95%CI: 1.42-2.32) and tuberculosis comorbidity
      (O.R. = 1.58; 95%CI: 1.17-2.79). In conclusion, high malaria prevalence was found
      in HIV patients accessing the out-patients centre of Sao Lucas of Beira. Our
      findings allowed us to identify the profile of HIV patients needing more medical
      attention: young adults, unemployed, with a low CD4 cell count and irregularly
      accessing to ART and cotrimoxazole prophylaxis.

PMID- 30227678
TI  - Effects of Formulation and Process Variables on Gastroretentive Floating Tablets
      with A High-Dose Soluble Drug and Experimental Design Approach.
AB  - To develop sustained release gastro-retentive effervescent floating tablets
      (EFT), a quality-based experimental design approach was utilized during the
      composing of a hydrophilic matrix loaded with a high amount of a highly water
      soluble model drug, metformin HCl. Effects of the amount of polyethylene oxide
      WSR 303 (PEO), sodium bicarbonate, and tablet compression force were used as
      independent variables. Various times required to release the drug, tablet tensile
      strength, floating lag time, tablet ejection force, and tablet porosity, were
      selected as the responses. Polymer screening showed that PEO had the highest gel
      strength among the various tested polymers. Sodium bicarbonate had the most
      significant effect on the release rate and floating lag time by retarding the
      rate from the hydrophilic matrices, whilst tablet compression force and PEO
      exerted the greatest influence on tablet properties (p < 0.0001). The design
      space was built in accordance with the drug release profiles, tensile strength,
      and floating lag time, following failure probability analysis using Monte Carlo
      simulations. The kinetic modeling revealed that the release mechanism was best
      described by the Korsmeyer-Peppas model. Overall, the current study provided a
      perspective on the systematic approach of gastro-retentive EFT, loaded with
      highly water-soluble drugs by applying quality by design concepts.

PMID- 30227679
TI  - Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential,
      and Neurosphere Generation.
AB  - Aberrant nitric oxide synthase 2 (NOS2) expression has been suggested as an
      interesting therapeutic target that is being implicated as a component of the
      molecular profile of several human malignant tumors, including glioblastoma,
      which is the most aggressive brain tumor with limited therapeutic options and
      poor prognosis. The aim of the present work was to evaluate the effect of 1400W,
      a specific NOS2 inhibitor, on human glioma cells in terms of clonogenic
      potential, proliferation, migration rate, and neurosphere generation ability.
      NOS2 expression was determined by Western blotting. Nitric oxide (NO) production
      was measured through nitrite level determination. The trypan blue exclusion test
      and the plate colony formation assay were performed to evaluate cell
      proliferation and clonogenic potential. Cell proliferation and migration ability
      was assessed by the in vitro wound-healing assay. Neurosphere generation in a
      specific stemcell medium was investigated. NOS2 was confirmed to be expressed in
      both the glioma cell line and a human glioma primary culture, and overexpressed
      in relative derived neurospheres. Experiments that aimed to evaluate the
      influence of 1400W on U-87 MG, T98G (glioblastoma cell lines) and primary glioma
      cells sustained the crucial role played by NOS2 in proliferation, colony
      formation, migration, and neurosphere generation, thus supporting the emerging
      relevance of a NOS2/NO system as a prognostic factor for glioma malignancy and
      recurrence.

PMID- 30227680
TI  - Crinipellins A and I, Two Diterpenoids from the Basidiomycete Fungus Crinipellis
      rhizomaticola, as Potential Natural Fungicides.
AB  - In the course of screening for microbes with antifungal activity, we found that
      the culture filtrate of the IUM00035 isolate exhibited strong antifungal activity
      against Magnaporthe oryzae and Colletotrichum coccodes in planta. Based on the
      phylogenetic analysis with the ITS region, the IUM00035 isolate was identified as
      Crinipellis rhizomaticola. To identify antifungal compounds from the C.
      rhizomaticola IUM00035 isolate, the culture filtrate of the isolate was
      partitioned with ethyl acetate and n-butanol and, consequently, two active
      compounds were isolated from the ethyl acetate extract. The chemical structures
      of the isolated compounds were determined as crinipellin A (1) and a new
      crinipellin derivative, crinipellin I (2), by NMR spectral analyses and a
      comparison of their NMR and MS data with those reported in the literature.
      Crinipellin A (1) exhibited a wide range of antifungal activity in vitro against
      C. coccodes, M. oryzae, Botrytis cinerea, and Phytophthora infestans (MICs = 1,
      8, 31, and 31 ug/mL, respectively). Furthermore, when plants were treated with
      crinipellin A (1) (500 ug/mL) prior to inoculation with fungal pathogens,
      crinipellin A (1) exhibited disease control values of 88%, 65%, and 60% compared
      with non-treatment control against tomato late blight, pepper anthracnose, and
      wheat leaf rust, respectively. In contrast to crinipellin A (1), crinipellin I
      (2) showed weak or no activity (MICs > 250 ug/mL). Taken together, our results
      show that the C. rhizomaticola IUM00035 isolate suppresses the development of
      plant fungal diseases, in part through the production of crinipellin A (1).

PMID- 30227681
TI  - Modification of Microelectrode Arrays with High Surface Area Dendritic Platinum
      3D Structures: Enhanced Sensitivity for Oxygen Detection in Ionic Liquids.
AB  - Electrochemical gas sensors are often used for identifying and quantifying redox
      active analyte gases in the atmosphere. However, for amperometric sensors, the
      current signal is usually dependent on the electroactive surface area, which can
      become small when using microelectrodes and miniaturized devices. Microarray thin
      film electrodes (MATFEs) are commercially available, low-cost devices that give
      enhanced current densities compared to mm-sized electrodes, but still give low
      current responses (e.g., less than one nanoamp), when detecting low
      concentrations of gases. To overcome this, we have modified the surface of the
      MATFEs by depositing platinum into the recessed holes to create arrays of 3D
      structures with high surface areas. Dendritic structures have been formed using
      an additive, lead acetate (Pb(OAc)2) into the plating solution. One-step and two
      step depositions were explored, with a total deposition time of 300 s or 420 s.
      The modified MATFEs were then studied for their behavior towards oxygen reduction
      in the room temperature ionic liquid (RTIL) [N8,2,2,2][NTf2]. Significantly
      enhanced currents for oxygen were observed, ranging from 9 to 16 times the
      current of the unmodified MATFE. The highest sensitivity was obtained using a two
      step deposition with a total time of 420 s, and both steps containing Pb(OAc)2.
      This work shows that commercially-available microelectrodes can be favorably
      modified to give significantly enhanced analytical performances.

PMID- 30227682
TI  - Prevalence of Metabolic Syndrome and Its Associated Factors among Vegetarians in
      Malaysia.
AB  - The prevalence and factors associated with metabolic syndrome (MetS) remain
      unknown in Malaysian vegetarians. This cross-sectional study aimed to determine
      the prevalence of MetS among vegetarians in Kuala Lumpur and Selangor and its
      associated factors. The data on socio-demographic characteristics, vegetarianism
      practises, lifestyle behaviours, body weight, height, waist circumference (WC),
      systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood
      glucose (FBG), and blood lipid profiles were collected from 273 vegetarians. A
      majority of the respondents were lacto-ovo vegetarians (44.0%), females (64.8%)
      and Chinese (54.9%). The prevalence of MetS was 24.2%. High BP (48.7%) and high
      WC (43.6%) were the most common MetS components. Females had lower WC, SBP, DBP,
      FBG, TG and higher HDL-c (p < 0.05) as compared to males. Multiple logistic
      regression analysis showed that being overweight and obese (Odds Ratio (OR) =
      7.74, 95% Confidence Interval (CI): 4.04-14.82) was the main risk factor of MetS
      after being adjusted for sex and age. This study found that one in four
      vegetarians had MetS. An intervention programme should be developed to reduce
      Body Mass Index (BMI) among vegetarians, especially among those who are found to
      be overweight and obese.

PMID- 30227683
TI  - Senior Secondary School Food Literacy Education: Importance, Challenges, and Ways
      of Improving.
AB  - Food literacy education at senior secondary school can provide both immediate and
      long-term benefits for adolescents. The exploration of multiple stakeholder
      groups' opinions regarding the importance, roles, and challenges of school food
      literacy education, and their suggestions for its improvement, will help the
      design and execution of future food literacy-related curricula and programmes.
      This study explored a broad range of Australian and international food, health,
      and education professionals' opinions regarding senior secondary school food
      literacy education through an online survey. One hundred and fifty-five food,
      health, and education professionals completed this survey between April and
      October 2017. Overall, the respondents strongly supported the need for food
      literacy education for senior secondary school students. Their suggestions for
      improving this form of education included: incorporation of relevant and up-to
      date content, the presence of strong practical components, offering food literacy
      as compulsory subjects or the incorporation of food literacy concepts into
      compulsory core subjects. Moreover, they proposed the active contribution of both
      internal and external stakeholders in the planning and delivery of this education
      to upgrade its quality and relevance. Overall, the findings suggest that a wide
      range of food, health, and education professionals are highly supportive of
      senior secondary school food literacy education and their constructive
      suggestions should be considered in school food literacy education enhancement
      efforts. Education authorities should seek ways of involving different
      stakeholders, including food-related professionals, in the design and delivery of
      food literacy education, and future studies should explore the best mechanisms
      for such involvement.

PMID- 30227684
TI  - A Crop Classification Method Integrating GF-3 PolSAR and Sentinel-2A Optical Data
      in the Dongting Lake Basin.
AB  - With the increasing of satellite sensors, more available multi-source data can be
      used for large-scale high-precision crop classification. Both polarimetric
      synthetic aperture radar (PolSAR) and multi-spectral optical data have been
      widely used for classification. However, it is difficult to combine the
      covariance matrix of PolSAR data with the spectral bands of optical data. Using
      Hoekman's method, this study solves the above problems by transforming the
      covariance matrix to an intensity vector that includes multiple intensity values
      on different polarization basis. In order to reduce the features redundancy, the
      principal component analysis (PCA) algorithm is adopted to select some useful
      polarimetric and optical features. In this study, the PolSAR data acquired by
      satellite Gaofen-3 (GF-3) on 19 July 2017 and the optical data acquired by
      Sentinel-2A on 17 July 2017 over the Dongting lake basin are selected for the
      validation experiment. The results show that the full feature integration method
      proposed in this study achieves an overall classification accuracy of 85.27%,
      higher than that of the single dataset method or some other feature integration
      modes.

PMID- 30227685
TI  - Energy-Efficient Online Resource Management and Allocation Optimization in Multi
      User Multi-Task Mobile-Edge Computing Systems with Hybrid Energy Harvesting.
AB  - Mobile Edge Computing (MEC) has evolved into a promising technology that can
      relieve computing pressure on wireless devices (WDs) in the Internet of Things
      (IoT) by offloading computation tasks to the MEC server. Resource management and
      allocation are challenging because of the unpredictability of task arrival,
      wireless channel status and energy consumption. To address such a challenge, in
      this paper, we provide an energy-efficient joint resource management and
      allocation (ECM-RMA) policy to reduce time-averaged energy consumption in a multi
      user multi-task MEC system with hybrid energy harvested WDs. We first formulate
      the time-averaged energy consumption minimization problem while the MEC system
      satisfied both the data queue stability constraint and energy queue stability
      constraint. To solve the stochastic optimization problem, we turn the problem
      into two deterministic sub-problems, which can be easily solved by convex
      optimization technique and linear programming technique. Correspondingly, we
      propose the ECM-RMA algorithm that does not require priori knowledge of
      stochastic processes such as channel states, data arrivals and green energy
      harvesting. Most importantly, the proposed algorithm achieves the energy
      consumption-delay trade-off as [ O ( 1 / V ) , O ( V ) ] . V, as a non-negative
      weight, which can effectively control the energy consumption-delay performance.
      Finally, simulation results verify the correctness of the theoretical analysis
      and the effectiveness of the proposed algorithm.

PMID- 30227686
TI  - Emergency Department Discharge Outcome and Psychiatric Consultation in North
      African Patients.
AB  - Studies in Europe have found that immigrants, compared to the local population,
      are more likely to seek out medical care in Emergency Departments (EDs). In
      addition, studies show that immigrants utilize medical services provided by EDs
      for less acute issues. Despite these observed differences, little is known about
      the characteristics of ED use by North African (NA) immigrants. The main
      objective of this study was to examine whether there were differences in ED
      discharge outcomes and psychiatric referrals between NA immigrants and Swiss
      nationals. A retrospective analysis was conducted using patient records from NA
      and Swiss adults who were admitted to the ED of the University Hospital in Bern
      (Switzerland) from 2013-2016. Measures included demographic information as well
      as data on types of admission. Outcome variables included discharge type and
      psychiatric referral. A total of 77,619 patients generated 116,859 consultations
      to the ED, of which 1.1 per cent (n = 1338) were consultations by NA patients.
      Compared to Swiss national patients, NA patients were younger, with a median age
      of 38.0 (IQR 28-51 years vs. 52.0 (IQR 32-52) for Swiss and predominantly male
      (74.4% vs. 55.6% in the Swiss). NA patient admission type was more likely to be
      "walk-in" or legal admission (7.5% vs 0.8 in Swiss,). Logistic regressions
      indicated that NA patients had 1.2 times higher odds (95% CI 1.07-1.40, p <
      0.003) of receiving ambulatory care. An effect modification by age group and sex
      was observed for the primary outcome "seen by a psychiatrist", especially for men
      in the 16-25 years age group, whereby male NA patients had 3.45 times higher odds
      (95% CI: 2.22-5.38) of having being seen by a psychiatrist. In conclusion
      differences were observed between NA and Swiss national patients in ED
      consultations referrals and outcomes, in which NA had more ambulatory discharges
      and NA males, especially young, were more likely to have been seen by
      psychiatrist. Future studies would benefit from identifying those factors
      underlying these differences in ED utilization.

PMID- 30227687
TI  - Compound Ammonium Glycyrrhizin Protects Hepatocytes from Injury Induced by
      Lipopolysaccharide/Florfenicol through a Mitochondrial Pathway.
AB  - Florfenicol (FFC), a widely used drug for chicken diseases, can aggravate
      lipopolysaccharide (LPS) damage to the liver. For this condition, natural or
      synthetic products displaying strong antioxidant capacity are expected to prevent
      LPS/FFC from inducing liver injury, so in our study, the compound ammonium
      glycyrrhizin (CAG) is used as the protective drug to decrease the injury to
      liver. The research aims to illustrate the underlying mechanism of combining LPS
      with FFC-induced liver injury and the protective role of CAG by using primary
      chicken hepatocytes as an in vitro model. The results show that LPS/FFC induced
      cell apoptosis and CAG protected hepatocytes from injury. The permeability of the
      cell membrane is elevated by LPS/FFC, leading to the efflux of enzymes (ALT,
      AST). Flow cytometry analysis indicates that LPS/FFC treatment increased the
      apoptosis rate significantly. Furthermore, with the up-regulation of apoptosis
      genes bax, cytochrome c and the down-regulation of bcl-2, caspase-3 and caspase-9
      are activated at the gene level. LPS/FFC-induced mitochondrial damage is
      accompanied by a significant decrease in mitochondrial membrane potential (MMP)
      and severe mitochondrial damage. However, CAG improves the situation for the
      purpose of protecting the liver. In conclusion, it is speculated that LPS/FFC
      induces severe liver injury through apoptosis and the CAG protects hepatocytes
      from injury via the mitochondria-mediated apoptosis pathway.

PMID- 30227691
TI  - B-Vitamin Therapy for Diabetic Nephropathy-Reply.

PMID- 30227689
TI  - Association of Wnt Inhibitors, Bone Mineral Density and Lifestyle Parameters in
      Women with Breast Cancer Treated with Anastrozole Therapy.
AB  - AIM: To determine the levels of Wnt inhibitors in patients treated with aromatase
      inhibitors (AIs) prior to therapy and to investigate their association with bone
      mineral density (BMD) and lifestyle parameters. METHODS: 137 breast cancer
      patients were divided into a group treated with 1 mg of anastrozole and a group
      w/o anastrozole therapy. Serum concentrations of sclerostin and dickkopf1 (DKK1)
      were measured by ELISA. BMD was measured by dual-energy X-ray absorptiometry
      (DXA). Lifestyle factors were investigated by a self-reported questionnaire.
      RESULTS: Sclerostin was significantly higher in the AI-treated group (31.8 pmol/L
      vs. 24.1 pmol/L; p < 0.001), whereas DKK1 was significantly lower in the AI
      treated group (24.3 pmol/L vs. 26.02 pmol/L; p < 0.001). Total hip and femoral
      neck BMD were significantly lower in the AI-treated group. CONCLUSION: AI
      treatment was associated with increased levels of sclerostin and decreased levels
      of DKK1.

PMID- 30227688
TI  - From Implantation to Birth: Insight into Molecular Melatonin Functions.
AB  - Melatonin is a lipophilic hormone synthesized and secreted mainly in the pineal
      gland, acting as a neuroendocrine transducer of photoperiodic information during
      the night. In addition to this activity, melatonin has shown an antioxidant
      function and a key role as regulator of physiological processes related to human
      reproduction. Melatonin is involved in the normal outcome of pregnancy, beginning
      with the oocyte quality, continuing with embryo implantation, and finishing with
      fetal development and parturition. Melatonin has been shown to act directly on
      several reproductive events, including folliculogenesis, oocyte maturation, and
      corpus luteum (CL) formation. The molecular mechanism of action has been
      investigated through several studies which provide solid evidence on the
      connections between maternal melatonin secretion and embryonic and fetal
      development. Melatonin administration, reducing oxidative stress and directly
      acting on its membrane receptors, melatonin thyroid hormone receptors (MT1 and
      MT2), displays effects on the earliest phases of pregnancy and during the whole
      gestational period. In addition, considering the reported positive effects on the
      outcomes of compromised pregnancies, melatonin supplementation should be
      considered as an important tool for supporting fetal development, opening new
      opportunities for the management of several reproductive and gestational
      pathologies.

PMID- 30227692
TI  - Fiber composition of the distal accessory flexor muscle in several decapod
      crustaceans.
AB  - The fiber composition of the distal accessory flexor muscle (DAFM) and the
      branching pattern of its excitor axon were compared in several species of crabs,
      in the lobster and the crayfish. The muscle is composed exclusively of long
      sarcomere (> 6 MUm) fibers and therefore of the slow type. In all the crab
      species, except one, there is a distal to proximal gradient of fibers with
      increasing sarcomere lengths; this gradient is reverse in lobsters and crayfish.
      A proximal to distal gradient of increasing fiber diameters occurs in the DAFM of
      all crab species but not in the lobster and crayfish, in which all the fibers are
      approximately equal in diameter. The single excitatory axon traverses the width
      of the DAFM and gives off primary branches on either side in the lobster and
      crayfish but on only one side in crabs. The hypothesis that the axonal branching
      pattern may govern the regional distribution of fibers with differing sarcomere
      lengths in proposed.

PMID- 30227690
TI  - Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon.
AB  - Congenital Pouch Colon (CPC) is a rare anorectal anomaly common to northwestern
      India, specifically Rajasthan. Despite efforts to understand the clinical genetic
      makeup of CPC, no attempt on identifying non-coding RNAs was done. We have
      earlier reported CPC's rare variants from whole exome sequencing (WES) across 18
      affected samples in a total of 64 subjects. A Smith-Waterman algorithm was used
      to infer a couple of lncRNAs from WES samples of CPC with predictions from the
      Noncode database. Further screening and quantification using polymerase chain
      reaction (PCR), we ascertained interactions using Micro Scale Thermophoresis
      (MST). We report the role of lnc-EPB41-1-1 shown to be promiscuously interacting
      with KIF13A substantiating their role in regulation.

PMID- 30227693
TI  - Fine structural analysis of the thoracic longitudinal stripes of Zaprionus
      vittiger (Diptera).
AB  - The structure of the longitudinal zebra stripes on the thorax of adult Zaprionus
      vittiger has been investigated by light-, polarization-, transmission electron-,
      and scanning electron microscopy. Each stripe consists of a central white stripe
      of about 50 MUm width and two lateral dark brown stripes about 30 MUm wide. Three
      different types of trichomes occur: Very long bent trichomes of the grooved-type,
      long bent trichomes of the crested-type, and short straight trichomes. The
      central white stripe contains neither bristle organs nor short straight trichomes
      but carries many long bent trichomes most of which are of the grooved type,
      contain two cavities and polarize the light in the polarization microscope. The
      dark brown stripes carry bristle organs and many trichomes of the short and
      straight-type. Bent trichomes of the crested-type are found on the whole zebra
      stripe at about equal frequencies; they contain no cavities and do not polarize
      the light. The cuticle of the dark stripes is underlain by pigment cells. It is
      suggested that the pigment granules in the epidermal cells cause the dark color
      of the dark brown stripes, whereas the form and structure of the bent grooved
      type trichomes cause the white color of the central stripe.

PMID- 30227694
TI  - Development of telotrophic-meroistic ovarioles of polyphage beetles with special
      reference to the formation of nutritive cords.
AB  - Oocytes and nurse tissue of Bruchidius differentiate from germ cells during the
      extended period of pupal development (7.2 +/- 0.6 days). A system of 15 pupal
      stages correlates ovarian development with changes in pigmentation of the eyes,
      maxillae, alae and tarsalia. The ovarioles grow in length at a constant rate,
      though their width does not change. A differentiating zone, consisting of germ
      cells and the basal layer of interstitial cells, arises at the base of the
      tropharium and separates presumptive oocytes and nurse cells. Early in pupal
      development the germ cells are arranged in primary syncytia with the cells
      connected by persisting intercellular bridges filled with fusomal material, never
      with larger particles, such as mitochondria. At later stages membrane
      disintegration changes the primary syncytium into a secondary one including all
      nurse cell nuclei. Nutritive cords are first noticeable when differentiation of
      oocytes and nurse cells starts. The cords seem to be of primary origin, i.e.,
      they are connections between sister cells which become elongated as these cells
      are separated during growth. This is indicated by the persistence of
      intercellular bridges which are sometimes found as part of the membrane of
      growing nutritive cords connecting young oocytes with the nurse cell syncytium.

PMID- 30227695
TI  - Histological and ultrastructural specialization of the digestive tract of the
      intestinal air breather hoplosternum thoracatum (teleost).
AB  - The digestive tract of Hoplosternum thoracatum consists of an esophagus, gastric
      area, anterior digestive intestine with elaborate folds, digestive intestine with
      decreasing folds and thin, smooth-surfaced respiratory intestine. The upper tract
      has a mucoid columnar lining which is gently folded, whereas the gastric area has
      numerous pits opening into the tubular secretory glands. Striated muscle
      comprises the anterior muscularis but is replaced by inner circular and outer
      longitudinal smooth muscle layers in the gastric region. The digestive intestinal
      mucosa is elaborately folded, consisting of columnar cells with prominent brush
      borders. Mucosa, submucosa, circular and longitudinal muscularis and serosa
      layers are present throughout the tract. Goblet cells occur in both the digestive
      and respiratory intestine. Major changes that appear in the respiratory intestine
      are a drastic reduction in mucosa epithelial thickness and the penetration of an
      elaborate capillary bed into the epithelium. The other basic layers are not
      significantly reduced in thickness. The air-blood barrier consists of the thin
      epithelium, basement lamina and very thin capillary endothelium. Regional
      cellular composition and ultrastructural features are correlated with respective
      digestive and respiratory functions.

PMID- 30227696
TI  - Fine structure of tarsal sensilla of Aedes aegypti (L.) (Diptera: Culicidae).
AB  - The tarsi of all three pairs of legs of both sexes of Aedes aegypti (L.) bear
      spine sensilla, five types of hair sensilla, which are designated A, B, C1, C2
      and C3, and campaniform sensilla. Type A and B hairs, spines, and cam-paniform
      sensilla are innervated by one neuron with a tubular body, a characteristic of
      cuticular mechanoreceptors. In particular the hairs and spines are tactile
      receptors and the campaniform sensilla are proprioceptors. The C1, C2, and C3
      hair sensilla have the morphological features of contact chemoreceptors. Type C1
      and C3 hairs are innervated by five and four neurons, respectively, which extend
      to the tip of the hair. Type C2 is innervated by five neurons, one of which
      terminates at the base of the hair in a tubular body while the remaining four
      extend to the tip of the hair. The role of the type C hairs in oviposition
      behavior, nectar feeding, and recognition of conspecific females is discussed.
      Presumed efferent neurosecretory fibers occur near the spine and hair sensilla.

PMID- 30227697
TI  - Fine structure and metamorphosis of the wax gland cells in a psyllid insect,
      Anomoneura mori schwartz (Homoptera).
AB  - The fine structure of the wax gland of Anomoneura nymph and its metamorphic
      change were investigated. In the nymph, this organ encircles the anus, and
      consists of two kinds of cells, derived from epidermal cells: (1) very tall, slim
      wax cells, which produce and secrete the wax, and (2) flat interstitial cells
      found among the wax cells. The whole gland is covered by a wax-secreting cuticle
      with a delicate surface sculpture. Each wax cell has a long, wide duct which
      opens at the cuticle and penetrates the entire cell. Its cytoplasm is rich in
      mitochondria and smooth endoplasmic reticulum while that of interstitial cells
      contains rough endoplasmic reticulum. During each nymphal molt, the cluster of
      primordial wax gland cells - derived from the epidermis - proliferates rapidly
      and forms the gland of the next instar. The gland of the preceding instar
      meanwhile degenerates. Interstitial cells play an important role in cuticle
      formation and shedding at each molt. These cells alone produce and deposit the
      new cuticle of the next instar; the wax cells, specialized for wax production,
      cannot produce cuticle. The apical portion of the wax cell is cut off from the
      main cell body by growth of the surrounding interstitial cells. Thereafter, the
      wax cells degenerate, resulting in the rapid disappearance of the previous
      instar's wax gland. Adults lack this gland entirely.

PMID- 30227698
TI  - Comparative studies on the circulatory system of the compound ascidians,
      Botryllus, Botrylloides and Symplegma.
AB  - The circulatory systems of four polystyelids, Botryllus schlosseri, B.
      primigenus, Botrylloides violaceus and Symplegma reptans, were compared. The
      palleal buds are connected to the parent zooid by a peduncle and to the colonial
      vascular system by connecting vessels. The peduncle of S. reptans disappears at
      an earlier stage of bud development than in B. primigenus; it survives the
      dissolution of the parent zooid in B. schlosseri and B. violaceus. The connecting
      vessel is formed by anastomosis between an epidermal outgrowth from the bud and a
      neighboring colonial vessel, and is characterized by the presence of a sphincter.
      The number of connecting vessels formed in a palleal bud is three in S. reptans,
      two in B. primigenus and one each in B. schlosseri and B. violaceus. In each
      species, the larva has eight rudiments of ampullae. In B. primigenus, the
      original ampullae degenerate soon after metamorphosis and new ampullae extend
      from the ventral epidermis of the oozooid. In the other species, the colonial
      vascular system is derived from the original ampullae. The whole colonial
      vascular system contracts and expands periodically, with regionally different
      phases. During each expansion cycle, the sphincter contracts once in B.
      primigenus and twice in S. reptans. The correlation may be due to blood pressure
      and the propagation of excitation through the colonial vascular system.

PMID- 30227699
TI  - Fine structure of the macronucleus during the cell division cycle of Euplotes
      eurystomus, a Ciliate Protozoon.
AB  - This paper reports new observations obtained from a study of macronuclear fine
      structure throughout various stages of the cell division cycle of Euplotes. Study
      of the ultrastructural organization of the macronuclear chromatin indicates that
      much of the chromatin is organized into continuous masses, portions of which
      appear to be attached to the nuclear envelope. The macronuclear envelope appears
      unchanged in the region of a replication band, and apparent attachments of the
      chromatin to the inner membrane of the nuclear envelope are maintained in the
      reticular and diffuse zones. Intranuclear helices were never observed in the
      diffuse zone. During macronuclear division, linear elements (fibrils or
      microtubules) were observed in close association with both chromatin bodies and
      nucleoli. The ultrastructural data suggest that the intranuclear linear fibrils
      have two functions: elongation of the dividing nucleus, and attachment of
      chromatin bodies and nucleoli to the envelope. The significance of these
      observations for macronuclear division and chromatin segregation is considered.

PMID- 30227700
TI  - Early events in sea urchin metamorphosis, description and analysis.
AB  - The larval epithelium of the sea urchin, Lytechinus pictus, consists of squamous
      cells and bands of columnar epithelial cells bearing cilia. During metamorphosis
      this tissue undergoes a series of rapid, complex changes. Through the scanning
      and transmission electron microscope, we describe and analyse these changes. The
      changes can be divided into three steps. (1) The larval arms bend away from the
      left side of the larva, exposing the urchin rudiment. Cells which are identical
      to smooth muscle cells are in a position to bring about this bending. (2) The
      squamous epithelial cells assume a cuboidal shape. This change in shape results
      in the collapse of the larval epithelium onto the presumptive aboral surface.
      These cells possess a subapical band of microfilaments. The cellular shape change
      but not the bending of the arms is reversibly inhibited by Cytochalasin B. These
      observations suggest a mechanism for this change. (3) The former lining of the
      vestibule of the urchin rudiment comes to lie over the collapsed larval tissue
      and forms the adult epithelium. At this point, after only one hour, the larva has
      assumed the external shape of an adult sea urchin.

PMID- 30227701
TI  - Modulatory multiplicity in the functional repertoire of the feeding mechanism in
      cichlid fishes. I. Piscivores.
AB  - Among piscivorous cichlids consistent differences have been recorded between
      ambush and pursuit hunters with respect to electromyographic, kinematic, pressure
      and behavioral profiles during prey capture by high speed inertial suction.
      Piscivorous cichlids possess a repertoire of at least two patterns of prey
      capture, each of which is characterized by an extreme regularity of the
      kinematic, pressure, electromyographic and behavioral profiles. The nature and
      locomotory behavior of the prey, visually analyzed by the predator during the
      prestrike stalk, determine which of the two preprogrammed patterns is recruited.
      Agile and elusive prey invariably will elicit a preprogrammed motor output
      (stereotyped motor pattern) that produces the greatest suction velocities in both
      ambush and pursuit hunters. The greater the kinematic and suction velocities, the
      greater the overlap of the firing sequences of antagonistic muscle complexes. The
      opercular and branchiostegal apparati function as an exceedingly effective anti
      backwash device, damping potential fluid oscillations within the oropharynx.
      Mastication occurs by triphasic movements and actions of muscles of the upper and
      lower pharyngeal jaws in both ambush and pursuit hunters. The lower pharyngeal
      jaw is acted upon by a force couple of which the fourth levator externus on one
      hand and the pharyngocleithralis externus and pharyngohyoideus on the other hand
      are the antagonistic components. Furthermore, the lower pharyngeal jaw is
      suspended by a muscular sling, the tension of which can be modified continuously.
      It is postulated that the switch from insectivorous to piscivorous feeding
      regimes (and perhaps vice versa) is accomplished by very minor structural and
      functional modifications, because the modulatory multiplicity and total range of
      repertories of the feeding machinery of the two trophic groups overlap
      significantly. Piscivorous cichlids may not have arisen by orthoselection in
      gradually-changing lineages, but represent the differential success of subsets
      from a random pool of speciation events. Adaptive features identified as
      characteristic for piscivory could have evolved in multiple and independent
      lineages at a punctuational mode and tempo.

PMID- 30227702
TI  - Assessment of fibrotic burden among chronic hepatitis B virus-infected patients
      with normal transaminase level.

PMID- 30227703
TI  - Leak after sleeve gastrectomy: how long do we have to be worried?

PMID- 30227704
TI  - Targeting Tumor Metabolism with Plant-Derived Natural Products: Emerging Trends
      in Cancer Therapy.
AB  - Recognition of neoplastic metabolic reprogramming as one of cancer's hallmarks
      has paved the way for developing novel metabolism-targeted therapeutic
      approaches. The use of plant-derived natural bioactive compounds for this
      endeavor is especially promising, due to their diverse structures and multiple
      targets. Hence, over the past decade, a growing number of studies have assessed
      the impact of phytochemicals on tumor cell metabolism, aiming at improving
      current knowledge on their mechanisms of action and, at the same time, evaluating
      their potential as anti-cancer metabolic modulators. In this Review, we focus on
      three classes of plant-derived compounds with promising anti-cancer activity
      phenolic compounds, isoprenoids, and alkaloids-to describe their effects on major
      energetic and biosynthetic pathways of human tumor cells. Such a comprehensive
      and integrated account of the ability of these compounds to hit different
      metabolic targets is expected to contribute to the rational design and critical
      assessment of novel anti-cancer therapies based on natural-product-mediated
      metabolic reprogramming.

PMID- 30227705
TI  - Influence of Ternary Complexation between Bovine Serum Albumin, Sodium Phytate,
      and Divalent Salts on Turbidity and In Vitro Digestibility of Protein.
AB  - Phytate decreases mineral and protein availability and influences protein
      properties, such as solubility and stability. The binding constants and turbidity
      data can help with the understanding of the influence of phytate and divalent
      salts on protein behavior. Ternary complexes formed between bovine serum albumin,
      sodium phytate, and divalent salts were investigated by isothermal titration
      calorimetry, turbidity, and in vitro protein digestibility. Results showed a
      positive entropy change and a negative and small enthalpy change as a result of
      electrostatic binding forces and ternary and binary complex precipitation. The
      interaction was favored for the systems containing calcium and manganese, whereas
      those containing magnesium showed a low heat of interaction. Despite the high
      protein digestibility, the stability of divalent phytates in a wide pH range may
      decrease mineral bioavailability. These results can provide important insights
      for the study of mineral bioavailability and diverse processes that involve
      protein and minerals in several areas of knowledge.

PMID- 30227706
TI  - Enhancing Pore-Environment Complexity Using a Trapezoidal Linker: Toward Stepwise
      Assembly of Multivariate Quinary Metal-Organic Frameworks.
AB  - Multicomponent metal-organic frameworks (MOFs) promise the precise placement of
      synergistic functional groups with atomic-level precision, capable of promoting
      fascinating developments in basic sciences and applications. However, the
      complexity of multicomponent systems poses a challenge to their structural design
      and synthesis. Herein, we show that linkers of low symmetry can bring new
      opportunities to the construction of multicomponent MOFs. A carbazole
      tetracarboxylate linker of  C s point group symmetry was designed and combined
      with an 8-connected Zr6 cluster to generate a low-symmetry MOF, PCN-609. PCN-609
      contains coordinatively unsaturated Zr sites arranged within a lattice with three
      crystallographically distinct pockets, which can accommodate linear linkers of
      different lengths. Sequential linker installation was carried out to
      postsynthetically insert three linear linkers into PCN-609, giving rise to a
      quinary MOF. Functionalization of each linker from the quinary MOF system creates
      multivariate pore environments with unprecedented complexity.

PMID- 30227708
TI  - A Preclinical Assessment of 89Zr-atezolizumab Identifies a Requirement for
      Carrier Added Formulations Not Observed with 89Zr-C4.
AB  - The swell of experimental imaging technologies to noninvasively measure immune
      checkpoint protein expression presents the opportunity for rigorous comparative
      studies toward identifying a gold standard. 89Zr-atezolizumab is currently in
      man, and early data show tumor targeting but also abundant uptake in several
      normal tissues. Therefore, we conducted a reverse translational study both to
      understand if tumor to normal tissue ratios for 89Zr-atezolizumab could be
      improved and to make direct comparisons to 89Zr-C4, a radiotracer that we showed
      can detect a large dynamic range of tumor-associated PD-L1 expression. PET/CT and
      biodistribution studies in tumor bearing immunocompetent and nu/nu mice revealed
      that high specific activity 89Zr-atezolizumab (~2 MUCi/MUg) binds to PD-L1 on
      tumors but also results in very high uptake in many normal mouse tissues, as
      expected. Unexpectedly, 89Zr-atezolizumab uptake was generally higher in normal
      mouse tissues compared to 89Zr-C4 and lower in H1975, a tumor model with modest
      PD-L1 expression. Also unexpectedly, reducing the specific activity at least 15
      fold suppressed 89Zr-atezo uptake in normal mouse tissues but increased tumor
      uptake to levels observed with high specific activity 89Zr-C4. In summary, these
      data reveal that low specific activity 89Zr-atezo may be necessary for accurately
      measuring PD-L1 in the tumor microenvironment, assuming a threshold can be
      identified that preferentially suppresses binding in normal tissues without
      reducing binding to tumors with abundant expression. Alternatively, high specific
      activity approaches like 89Zr-C4 PET may be simpler to implement clinically to
      measure the broad dynamic range of PD-L1 expression known to manifest among
      tumors.

PMID- 30227709
TI  - Transformation of AgCl Particles under Conditions Typical of Natural Waters:
      Implications for Oxidant Generation.
AB  - The engineered silver nanoparticles (AgNPs) used in consumer products are
      ultimately released to the environment either as Ag(0), silver sulfide (Ag2S(s)),
      silver chloride (AgCl(s)), and/or dissolved Ag(I) complexes. Of these, AgCl(s)
      and Ag2S(s) exhibit semiconducting properties and hence may have significant
      implications to oxidant generation and subsequent redox transformations in
      natural waters. In this work, we investigate the transformation and
      photoreactivity of AgCl(s) under simulated natural water conditions with the
      photoreactivity probed by measuring the oxidation of formate (HCOO-), a simple
      compound with a well-defined oxidation pathway. Our results show that AgCl(s)
      undergoes rapid dissolution in the presence of chloride concentrations
      representative of seawater (ca. 0.5 M NaCl) forming dissolved Ag(I) complexes but
      is stable in fresh waters and slightly brackish waters (<=200 mM NaCl). We
      further show that under these lower salinity conditions in which AgCl(s) is
      stable, pH has a significant impact on the reactivity of semiconducting AgCl(s).
      The photoreactivity (measured as initial HCOO- oxidation rate) of AgCl(s) is
      relatively constant at pH 4.0 for periods of 24 h or more; however, it decreases
      rapidly under alkaline conditions. The rapid transformation (or "aging") of
      AgCl(s) under alkaline conditions suggests that AgCl(s), potentially transported
      through wastewater effluent to fresh or brackish water environments, may not have
      a significant impact in such environments. In comparison, in situ formed AgCl(s),
      potentially formed as a result of the oxidation of high concentrations (>=60 MUg
      Ag.L-1) of Ag(0) and/or Ag2S(s), may have significant implications to oxidant
      generation in natural waters. Our results further show that rapid cycling of Ag
      between the 0 and +I redox states in sunlit surface waters as a result of the
      presence of AgNP oxidants (such as H2O2 and organic radicals) will further
      enhance the rate and extent of oxidant generation by AgCl(s).

PMID- 30227707
TI  - Could Fecal Phenylacetic and Phenylpropionic Acids Be Used as Indicators of
      Health Status?
AB  - Although most of the health effects attributed to polyphenols may be linked to
      their phenolic-derived metabolites, the role of the intestinal derived-phenolics
      in human health is still far from being well understood. We determined the
      profile of fecal phenolic-derived metabolites, microbiota, biomarkers of
      oxidative stress and inflammation, and daily intake of bioactive compounds in 71
      elderly volunteers. Phenylacetic and phenylpropionic acids were the main phenolic
      metabolites present in feces. From them, phenylacetic acid was related with a
      more pro-oxidant and immune stimulated status, and both were negatively
      associated with fecal propionate, whereas phenylpropionic acid was directly
      related with the fecal concentration of acetate. Moreover, phenylacetic acid was
      negatively associated with the Bacteroides group and Clostridium cluster XIVa and
      positively with Lactobacillus. These results provide a rationale to explore the
      potential of fecal microbial phenolic-derived metabolites as possible biomarkers
      of health status in future studies focused on the elderly population.

PMID- 30227710
TI  - Cosensitization Strategy with Cascade Energy Level Arrangement for Ultrasensitive
      Photoelectrochemical Protein Detection.
AB  - Here, a photoelectrochemical (PEC) biosensor was established by a cosensitization
      strategy with cascade energy level arrangement for ultrasensitive detection of
      prostate-specific antigen (PSA). The proposed cosensitization strategy was based
      on the well-matched energy level arrangement of four kinds of organic photoactive
      materials, in which poly{4,8-bis[5-(2-ethylhexyl)thiophen-2-yl]benzo[1,2- b:4,5-
      b']dithiophene-2,6-diyl- alt-3-fluoro-2-[(2-ethylhexyl)-carbonyl]thieno[3,4-
      b]thiophene-4,6-diyl} (PTB7-Th) was used as the photoactive material and
      perylenetetracarboxyl diimide (PDI), fullerene (nano-C60), and polyaniline (PANI)
      were employed as the sensitizers. The resulting PTB7-Th/PDI/nano-C60/PANI cascade
      cosensitization structure with narrow energy level gradient (<0.54 eV) could
      effectively improve electron transfer capability, obviously raise light energy
      utilization and significantly enhance photoelectric conversion efficiency,
      leading to dramatically enhanced photocurrent response. Using PSA as a target
      model, the proposed PEC biosensor exhibited high sensitivity and excellent
      stability with a wide detection range from 1 fg/mL to 0.1 ng/mL and a detection
      limit of 0.43 fg/mL. Moreover, the proposed PEC biosensor provides a cascade
      cosensitization strategy that could significantly improve PEC performances and
      open up a promising platform to establish high selectivity, stability, and
      ultrasensitive analytical techniques.

PMID- 30227711
TI  - Structure-Based Drug Design and Identification of H2O-Soluble and Low Toxic
      Hexacyclic Camptothecin Derivatives with Improved Efficacy in Cancer and Lethal
      Inflammation Models in Vivo.
AB  - Camptothecin (CPT) has been shown to block disassembly of the topoisomerase I
      (Topo I)/DNA cleavable complex. However, the poor aqueous solubility, intrinsic
      instability, and severe toxicity of CPTs have limited their clinical
      applications. Herein, we report the design and synthesis of H2O-soluble and
      orally bioavailable hexacyclic CPT derivatives. By analysis of a virtual chemical
      library and cytotoxicity screening in vitro, 9 and 11 were identified as
      potential prodrugs and chosen for further characterization in vivo. Both
      compounds exhibited remarkable anticancer and anti-inflammation efficacies in
      animals and improved drug-like profiles.

PMID- 30227712
TI  - Singlet-Fission-Born Quintet State: Sublevel Selections and Trapping by
      Multiexciton Thermodynamics.
AB  - Singlet fission (SF) is expected to exceed the theoretical limit of the solar
      cell efficiency. Quintet (Q) state generation in triplet-triplet pair is
      essential for preventing the unwanted loss of SF-born multiexciton through
      singlet channels, although little is known on the primary multiexciton spin
      dynamics following the intermolecular SF. In this study, time-resolved EPR
      revealed the intermolecular multiexciton dynamics, energetics and geometries in
      aggregated 6,13-bis(triisopropylsilylethynyl)pentacene and 2-phenyl-6,11
      bis(triisopropylsilylethynyl)tetracene in diluted frozen solution. We have
      demonstrated sublevel selective generations of excited quintet states (|Q0?, |Q
      1? and |Q-2?) by singlet-quintet (SQ) mixings during triplet-exciton diffusions
      within geminate multiexcitons. The present fundamental characteristics of the
      quintet generations shows strong impact of coexistence of molecularly ordered
      "hot spot" and disordered regions for exergonic SQ mixings driven by entropy,
      thereby paving a new avenue for rational designs of organic devices with
      controlled multiexciton dynamics by optimizing film morphologies.

PMID- 30227713
TI  - Organic Semiconductor Laser Platform for the Detection of DNA by AgNP Plasmonic
      Enhancement.
AB  - Organic semiconductor lasers are a sensitive biosensing platform that respond to
      specific biomolecule binding events. So far, such biosensors have utilized
      protein-based interactions for surface functionalization but a nucleic acid-based
      strategy would considerably widen their utility as a general biodiagnostic
      platform. This manuscript reports two important advances for DNA-based sensing
      using an organic semiconductor (OS) distributed feedback (DFB) laser. First, the
      immobilization of alkyne-tagged 12/18-mer oligodeoxyribonucleotide (ODN) probes
      by Cu-catalyzed azide alkyne cycloaddition (CuAAC) or "click-chemistry" onto an
      80 nm thick OS laser film modified with an azide-presenting polyelectrolyte
      monolayer is presented. Second, sequence-selective binding to these immobilized
      probes with complementary ODN-functionalized silver nanoparticles, is detected.
      As binding occurs, the nanoparticles increase the optical losses of the laser
      mode through plasmonic scattering and absorption, and this causes a rise in the
      threshold pump energy required for laser action that is proportional to the
      analyte concentration. By monitoring this threshold, detection of the
      complementary ODN target down to 11.5 pM is achieved. This complementary binding
      on the laser surface is independently confirmed through surface-enhanced Raman
      spectroscopy (SERS).

PMID- 30227714
TI  - What Papers Are People Citing and What Are People Reading?

PMID- 30227715
TI  - In This Issue, Volume 9, Issue 9.

PMID- 30227717
TI  - Interactions of bioactive molecules with thin dendritic glycopolymer layers.
AB  - The authors report on highly swellable, stable layers of spherical dendritic
      glycopolymers, composed of hyperbranched poly(ethylene imine) (PEI) as core and
      two different maltose shells (A = dense shell and B = open shell). These
      glycopolymers are cross-linked and attached with poly(ethylene-alt-maleic
      anhydride) (PEMA) or citric acid on SiOx substrates. The swelling and adsorption
      of biomolecules were analyzed by spectroscopic ellipsometry and quartz crystal
      microbalance with dissipation. The swelling degree and complexation with the drug
      molecule adenosine triphosphate (ATP) were found to be up to 10 times higher for
      dendritic glycopolymer layers cross-linked with PEMA than for layers cross-linked
      with citric acid. ATP complexation by electrostatic interaction with the PEI
      cores was confirmed by x-ray photoelectron spectroscopy analysis. Complexation
      led to partial collapsing, stiffening, and increase of polymer layer viscosity of
      the PEMA cross-linked layers. From modeling of ellipsometric data, it was deduced
      that ATP complexation preferably takes place at the polymer layer-solution
      interface. The size effect of the adsorbates was investigated by comparing ATP
      complexation with the adsorption of larger vitamin B12 and human serum albumin
      (HSA) protein. PEI-Mal A cross-linked with PEMA was found to be resistant toward
      B12 and HSA adsorption due to the diffusion barrier of the polymer layer. Thus,
      the authors present potentially biocompatible polymer surfaces for drug loading
      and their surface supported release.

PMID- 30227718
TI  - Effect of a participatory patient education programme (NExt EDucation) in group
      based patient education among Danes with type 2 diabetes.
AB  - Objective To assess the effect of a participatory group-based education programme
      for individuals with type 2 diabetes, Next Education. Method In a quasi
      experimental study, individuals with type 2 diabetes were recruited from 14
      Danish municipalities with a patient education programme. Eight municipalities
      using Next Education were intervention sites; six control sites used usual group
      based education programmes. Data were collected through questionnaires at
      baseline and at 3 and 12 months after programmes ended. Changes in quality of
      life (EQ-5D-5L), diabetes-related emotional distress (PAID-5), physical activity,
      diet, foot care and sense of coherence (SOC-13) were assessed in generalised
      linear mixed models. Results At baseline, 310 participants (52.6% females, mean
      age 62.5 years [SD = 10.7] and a mean duration of type 2 diabetes of 6.9 years
      [SD = 8.4]) participated in Next Education ( n = 234) or group-based education (
      n = 76) at control sites. Compared with participants at control sites,
      participants at intervention sites had significantly larger sense of coherence
      scores at 3 (9.4%, p = 0.03) and 12 (9.8%, p = 0.02) months of follow-up. Other
      measures did not differ significantly between groups. Discussion It is likely
      that person-centeredness and high degrees of user participation at the
      intervention sites improved sense of coherence among Danes with type 2 diabetes.

PMID- 30227719
TI  - Institutional distrust among gay, bisexual, and other men who have sex with men
      as a barrier to accessing pre-exposure prophylaxis (PrEP).
AB  - Populations at highest risk for acquiring HIV are more likely to pass through
      criminal justice (CJ) settings, and CJ-involved individuals are often at the
      intersection of multiple overlapping risk factors. The present study explored
      interest in, knowledge of, and barriers to PrEP uptake among gay, bisexual, and
      other men who have sex with men involved in the criminal justice system. Using
      semi-structured interviews, 26 participants who identified as MSM were asked
      about PrEP knowledge and interest, HIV risk, and incarceration experience. One
      theme that emerged across interviews was how institutional distrust in CJ
      settings may instill lack of trust in medical care after perceived mistreatment.
      Participants explained how lack of privacy fostered feelings that medical care
      was not confidential, care received was tied to status as an incarcerated person,
      and feelings of dehumanization led to distrust. Findings explore how distrust may
      hinder PrEP uptake and other HIV prevention efforts in CJ settings as well as
      after release. They highlight the need for greater privacy efforts and cultural
      humility, and explore how medical settings may function as spaces for people who
      are incarcerated to disclose HIV risk status. Few studies to our knowledge have
      examined the role of institutional distrust on men who have sex with men (MSM) in
      the context of pre-exposure prophylaxis (PrEP) interventions. The present study
      has implications for creating best practices to structure HIV prevention
      interventions in CJ settings.

PMID- 30227720
TI  - The Use of tPA in the Treatment of Frostbite: A Systematic Review.
AB  - BACKGROUND: The use of tissue plasminogen activator (tPA) for the treatment of
      frostbite has been reported and advocated, but its efficacy has not been well
      established. We conducted a systematic review to guide physicians on the role of
      tPA in the treatment of frostbite. Our hypothesis was that the use of tPA
      improves clinical outcomes, as measured by amputation rate. METHODS: We searched
      MEDLINE (PubMed) and EMBASE for primary research articles on the use of tPA for
      the treatment of extremity frostbite. Information related to study design,
      outcomes, and complications was extracted. A total of 204 citations were
      screened, and then 35 abstracts and 24 reports were reviewed. Fifteen studies met
      the standard for final review. RESULTS: One randomized, prospective study; 3
      cohort studies; 8 case series; and 3 case reports were found. A total of 208
      patients were treated. Differences in protocols, inclusion criteria, and outcomes
      measures prevented combining the study results. In all the studies, the authors
      reported that the use of tPA was or may have been useful in reducing amputation
      rates or increasing tissue salvage. Complication rates ranged from 0% to 100%,
      with a combined rate of 13%. The quality of the evidence was low. CONCLUSIONS:
      Due to the low scientific quality of the studies, the efficacy of tPA in reducing
      amputation rates cannot currently be established. Randomized, prospective trials
      or well-controlled cohort studies are needed to better assess the role of tPA.
      Consideration should be given to limiting its use to research protocols.

PMID- 30227721
TI  - Low wear rate at 6-year follow-up of vitamin E-infused cross-linked polyethylene:
      a randomised trial using 32- and 36-mm heads.
AB  - BACKGROUND: Free radicals formed in the cross-linking process may over time alter
      the mechanical properties of highly cross-linked polyethylene. Vitamin E-infused
      highly cross-linked polyethylene was therefore developed to achieve low wear-rate
      and good mechanical properties in the long term. AIM: To present 6-year results
      from the initial randomised controlled trial. PATIENTS AND METHODS: We measured
      wear and periacetabular bone remodelling in cementless total hip arthroplasty; 32
      or 36-mm Biolox Delta heads and vitamin E-infused highly cross-linked
      polyethylene (E-Poly) were used. Markerless radiosterometric analysis measured
      the in vivo wear and dual energy x-ray absorptiometry was used to analyse bone
      remodelling in 40 hips at 6-year follow-up. RESULTS: In the proximal direction
      the wear for 32- and 36-mm heads was 0.15 mm (95% confidence interval [CI], 0.08
      0.21) and 0.06 mm (95% CI, -0.002-0.12), respectively ( p = 0. 015). However,
      between 3 months and 6 years (excluding the period of "bedding in"), the proximal
      wear for 32- and 36-mm heads was 0.10 mm (95% CI, 0.05-0.15) and 0.05 mm (95% CI,
      -0.01-0.11), respectively ( p = 0.12). The annual proximal wear rate for 32- and
      36-mm heads from 3 months to 6 years was 0.02 mm and 0.01 mm, respectively. There
      was no difference in bone remodelling around the cup from baseline to 6 years for
      the total material and no differences between study groups. CONCLUSION: Wear of
      this vitamin E-infused highly cross-linked polyethylene is still low at 6-year
      follow-up, with no significant difference in wear from 3 months to 6 years
      between 32- and 36-mm heads.

PMID- 30227722
TI  - Development of the Care Environment Scale-Long-Term Care.
AB  - A critical dimension of Quality Assurance and Performance Improvement (QAPI)
      activity in long-term care is an analysis of the care environment, that is, the
      way care and services are organized. The purpose of this study was to develop and
      pilot test a psychometrically sound tool that long-term care staff could use to
      assess the care environment and guide performance improvement activity. Focus
      groups with 57 interdisciplinary participants in five nursing homes developed
      initial items, with excellent content validity (item content validity index =
      1.0) evaluated by an expert panel. Pilot testing of internal consistency of the
      Care Environment Scale-Long-Term Care (CES-LTC) was conducted in a web-based
      administration of the items by 425 interdisciplinary staff members in 30 nursing
      homes and four assisted living facilities. The CES-LTC is internally consistent
      (Cronbach's alpha = .90) and accounts for approximately 71.6% of the total
      variance. The three factors extracted from the exploratory factor analysis are
      Institutional Values ( k = 6), Access to Resources ( k = 10), and Person-Centered
      Approaches ( k = 12). Intrarater reliability in a subsample of 66 registered
      nurses revealed good test-retest results (overall intraclass correlation
      coefficients [ICC] = 0.78). The CES-LTC appears to be a valid and reliable
      measure of staff perceptions of the care environment and may be used to actively
      engage staff in QAPI endeavors including root cause analyses and improvement
      activity.

PMID- 30227723
TI  - 90-Day Hospital Readmissions of Patients in a Geriatric Acute Care Ward in
      Singapore.
AB  - The objective of the study is to examine the 90-day readmission rate and identify
      the predictors for 90-day readmissions at a geriatric ward in a tertiary hospital
      in Singapore. A secondary analysis of case-control data was performed. Data of
      patients discharged from a geriatric ward between January 2015 and January 2016
      were retrieved from an existing data set. Out of 564 index admissions involving
      older adults, the 90-day geriatric readmission rate was 10.1%. Activities of
      daily living dependency (odds ratio [OR]: 0.988, 95% confidence interval [CI]:
      [0.978, 0.999]) and living with the spouse (OR: 2.988, 95% CI: [1.388, 6.432])
      were identified as significant predictors of 90-day geriatric readmissions. The
      study suggests that rehabilitation to restore the geriatric patient's ability to
      perform daily activities and adequate caregiver training for the spouse are
      essential in reducing geriatric readmissions. Also, postdischarge follow-up with
      both the patient and caregiver can greatly reduce the risk of readmission in
      geriatric patients.

PMID- 30227724
TI  - Hepatic enhancement differences when dosing iodinated contrast media according to
      total versus lean body weight.
AB  - Background Recent studies suggest potentially improved inter-patient variability
      in hepatic enhancement by dosing contrast media (CM) according to lean body
      weight (LBW); however, studies vary in dosing strategy and most involved solely
      Japanese patients. Purpose To compare the magnitude and inter-patient variability
      in mean hepatic enhancement (MHE) when dosing CM according to total body weight
      (TBW) versus LBW in a Western population. Material and Methods With ethics
      approval, this study comprised two parts: (i) 100 CTs acquired with 1.3 mL Isovue
      370/kg TBW were analyzed; (ii) 108 patients were consented for LBW dosing at 1.9
      mL/kg (max. 150 mL, both groups). Liver attenuations were obtained from regions
      of interest. The MHE, MHE per gram of iodine (MHE/I), and adjusted MHE (aMHE =
      MHE/(I/TBW or LBW)) were calculated. We compared patient populations (Fisher's
      exact test, t-tests) and inter-patient variability (F-tests of variances in MHE)
      and performed linear regressions of MHE and aMHE. Results Cohorts were similar in
      age, sex, TBW, LBW, and total CM dose. MHE was higher in part 2 (63.1 +/- 13 vs.
      56.3 +/- 12 HU, P = 0.0001) but variances were similar ( P > 0.7). In part 2, men
      received more CM ( P = 0.0002) and MHE was higher ( P = 0.0002); women received
      less CM ( P = 0.053) but showed a non-significant trend for greater MHE ( P =
      0.07). MHE/I was higher for women in part 2 ( P = 0.01) and stable in men ( P =
      0.72). Linear regressions showed no lines of best-fit with non-zero slopes, for
      both sexes and study parts. Conclusion With CM dose constant, LBW dosing yielded
      a higher magnitude in MHE but did not reduce inter-patient variability.

PMID- 30227725
TI  - Acute and delayed effects of concentric and eccentric exercise on quantitative
      muscle MRI.
AB  - Background Advanced magnetic resonance imaging (MRI) is capable of identifying
      subtle effects of exercise. However, it is unclear whether it is sensitive enough
      to differentiate between different contractions. Purpose To compare the acute and
      delayed effects of concentric and eccentric exercise on quantitative MRI in
      hamstring muscles. Material and Methods Participants performed eccentric and
      concentric leg curls. Quantitative T2 and magnetization transfer ratio (MTR) maps
      were calculated in the hamstring complex before exercise, 30 minutes, 24 hours, 7
      days, and 14 days after exercise. Results Compared to baseline, significant MTR
      reduction (-7.3%) and T2 elevation (72.2%) were observed in the semitendinosus
      muscle (ST) at 24 hours after eccentric exercise ( P = 0.04). Concentric
      contractions induced T2 elevation in the ST (20.8%) and biceps femoris (5.1%)
      muscles at 30 minutes after exercise ( P = 0.04) which normalized within 24
      hours. Conclusions Longitudinal effects of concentric and eccentric exercise can
      be detected by both T2 and MTR, but T2 is more sensitive to subtle alterations.

PMID- 30227726
TI  - Eustachian Tube Balloon Dilation: Emerging Practice Patterns for a Novel
      Procedure.
AB  - OBJECTIVES: To review the role of eustachian tube balloon dilation (ETBD) in the
      setting of chronic Eustachian tube dysfunction (ETD) and ascertain how ETBD is
      currently being used in practice today. METHODS: An online survey included 20
      questions designed by 3 investigators to examine how otolaryngologists utilize
      ETBD in the management of ETD. The survey was distributed to the members of the
      American Rhinologic Society (ARS), American Otological Society (AOS), and
      American Neurotology Society (ANS) in their respective annual electronic mailings
      in April and May of 2017. RESULTS: A total of 1105 and 633 surveys were sent to
      ARS and AOS/ANS members, respectively. Of those, 157 surveys were returned (126
      from ARS and 31 from AOS/ANS). Of those returning the survey, 72 (50%) had not
      performed ETBD and were excluded from subsequent analysis. Forty-four (66%)
      respondents consider ETBD after failure of medical management; conversely, 18
      (27%) and 26 (39%) consider ETBD after failure of 1 or more trial of myringotomy
      tube placement. Routine testing for ETBD includes audiogram with tympanometry 64
      (96%) and preoperative computer tomography (CT) 38 (57%). Fifty-three (80%)
      practitioners only perform ETBD in adults 18 years and older. Thirty-four (53%)
      respondents describe ETBD as "great" or "good," while 27 (42%) were unsure, and
      only 3 (5%) did not like ETBD. CONCLUSIONS: Eustachian tube balloon dilation is a
      novel technique for the treatment of chronic ETD, and its role continues to
      evolve and develop. Current practice patterns demonstrate wide variability in the
      assessment of ETD, heterogeneity in the timing of ETBD, and controversy in
      preoperative CT screening.

PMID- 30227727
TI  - A Comparison of Barbed Suture Versus Traditional Techniques for Muscle Belly
      Repair.
AB  - BACKGROUND: The use of barbed sutures in wound closure and tendon repair has been
      previously been studied with improved results over traditional suture material.
      We examine the use of barbed suture in muscle belly repair in a custom
      configuration, comparing it with traditional configurations and a control.
      METHODS: Twenty-five matched porcine psoas muscles were assigned to 5 different
      test groups: Mason-Allen with #1 Ethibond, Figure of Eight Allen with #1
      Ethibond, Modified Kessler with #1 Ethibond, Custom Configuration with #2 Barbed
      PDS, Custom Configuration with #1 Ethibond. Repair was performed on the cut edge
      of muscle, with the free end of the suture anchored to a fixed base, forming a
      single-sided repair. An Instron 8874 tensiometer was used to linearly distract
      the repair to failure at 1 mm/s after 1 N preload. Five samples of each group
      were run, comparing load to failure and distraction at 10 N. RESULTS: Repair with
      barbed suture in custom configuration had statistically significantly greater
      load to failure than all other methods. It also showed statistically significant
      less displacement at 10 N of force than all other methods of repair except the
      Mason-Allen repair with #1 Ethibond. Mode of failure for traditional techniques
      was suture pull-through with tissue loss. Failure with barbed suture was through
      suture pullout without tissue loss. CONCLUSIONS: Custom configuration with a
      barbed suture increases the load to failure and decreases displacement of the
      repair site at 10 N of force. In addition, when the suture does pull out, it does
      so with minimal tissue loss.

PMID- 30227728
TI  - A Literature Review of Factors Influencing Injurious Falls.
AB  - Falls pose substantial challenges to health care institutions. This review aims
      to provide a synthesis and critique of studies that investigated fall injury risk
      factors and to identify significant risk factors that predispose patients to
      injurious falls. A comprehensive literature search was conducted in PubMed,
      COCHRANE, Embase, Cumulative Index to Nursing and Allied Heath Literature, and
      Scopus. Additional records were searched through Google Scholar and
      bibliographies of the retrieved articles. Twenty-three primary research studies
      were included. Demographic, intrinsic, and extrinsic factors have been
      identified. Demographics include age, gender, and marital status. Intrinsic
      factors include body mass index, medication, and preexisting conditions, and
      extrinsic factors include environmental factors. Several factors were found to be
      inconclusive. These factors should be considered and examined further. Future
      research may evaluate interventions focusing on targeted risk factors of
      injurious falls. Clinical guidelines addressing the factors in this review may be
      considered after further testing and research.

PMID- 30227730
TI  - I Don't Know.

PMID- 30227729
TI  - Novel cardiovascular risk biomarkers in carotid atherogenesis.

PMID- 30227731
TI  - Comparison of efficacy of oral paracetamol versus ibuprofen for PDA closure in
      preterms - a prospective randomized clinical trial.
AB  - BACKGROUND: Currently nonselective cyclooxygenase (COX) inhibitors, ibuprofen and
      indomethacin, are approved drugs for closure of patent ductus arteriosus but have
      potential toxicities. There are reports of the effectiveness of paracetamol in
      ductal closure. However, there is paucity of data comparing paracetamol to
      ibuprofen or indomethacin in relation to the efficacy and safety profile.
      METHODS: This randomized clinical trial was done in our tertiary care neonatal
      unit from October 2014 to January 2016 after clearance from ethical committee. It
      was registered with clinical trial registry of India (CTRI/2016/09/007261) and
      drug controller general of India (CT/Drugs/56/2014). Preterm neonates with
      clinical suspicion of hemodynamically significant PDA after echo confirmation
      were included in the study. Randomization was done by stratified randomization
      through sealed opaque envelopes. A sample size of 150 was estimated with an
      expected difference in success of closure as 20% between the treatment groups at
      level of 5% significance and 80% power. The echocardiography was done 24 hours
      after completion of treatment by a cardiologist blinded to treatment. RESULTS:
      The baseline parameters were comparable between two groups. One hundred and forty
      six babies had hs-PDA, out of which 110 babies were randomized. No significant
      difference was found between the two groups with respect to PDA closure (RR 0.97,
      95%CI 0.78-1.20, p = 1), mortality or cardio-respiratory morbidity. The babies
      who received ibuprofen had a higher occurrence of acute kidney injury (RR 0.33,
      95%CI 0.13-0.85, p = 0.024). CONCLUSIONS: Paracetamol is as effective as
      ibuprofen for PDA closure in preterm neonates. Ibuprofen used for PDA closure in
      preterms poses an increased risk for acute kidney injury compared to paracetamol.

PMID- 30227732
TI  - Certification in Medical Quality.

PMID- 30227733
TI  - [Rapidly progressive proliferative glomerulonephritis with monoclonal
      immunoglobulin G deposits despite the mild histological changes. Case report].
AB  - Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits
      is characterized by granular deposits of monoclonal IgG; histologically it has
      typically a membranoproliferative or endocapillary pattern, and seen
      electronmicroscopically there are dense deposits without substructure. Here, we
      present the case of a 62-year-old Caucasian woman who was admitted with rapidly
      progressive kidney failure. The patient's status, the laboratory and imaging
      examinations did not support prerenal, postrenal and - among the intrinsic causes
      - vascular and tubulointerstitial origin. The proteinuria and dysmorphic
      microhematuria suggested rapidly progressive glomerulonephritis. Tests for anti
      neutrophil cytoplasmic antibodies, anti-glomerular basement membrane, antinuclear
      antibodies and cryoglobulins were negative, the C3 and C4 levels were normal. The
      biopsy evaluation diagnosed proliferative glomerulonephritis with monoclonal IgG
      deposits because of mesangial granular deposits of IgG3-kappa, C3, and C1q, and
      ultrastructurally electron-dense deposits (incidence in our adult native kidney
      biopsy series: 0.18%). 31 glomeruli were assessed histologically. 29 glomeruli
      displayed mild mesangial hypercellularity, 2 glomeruli were globally sclerotic.
      Crescents were not observed. Mild arteriolar hyalinosis, interstitial fibrosis
      and tubular atrophy accompanied the glomerular alterations. In the postbiopsy
      evaluation, paraprotein or multiple myeloma was not detected. Despite the mild
      histological findings, the kidney failure progressed, and hemodialysis had to be
      started two weeks after the biopsy. Steroids, cyclophosphamide and rituximab did
      not affect her kidney function, and she remained on hemodialysis during the
      follow-up of 39 months. This report presents for the first time proliferative
      glomerulonephritis with monoclonal IgG deposits as the possible cause of rapidly
      progressive nephritic syndrome in the absence of pronounced glomerular
      proliferative, sclerotic or tubulointerstitial lesions. Orv Hetil. 2018; 159(38):
      1567-1572.

PMID- 30227734
TI  - [Pre-travel advice for the Hungarian pilgrims of El Camino. Travel risks and
      instructions].
AB  - The Way of St. James (El Camino) is getting more and more popular. Analysis of
      the age groups of the pilgrims shows that the number of young pilgrims (30<
      years) is decreasing, but the number of middle-aged people (30-60 years) is
      slightly increasing, while the number of elderly people (>60 years) has
      considerably increased. The statistical data of the Pilgrims' office in Santiago
      de Compostela also display the continuous elevation in the number of the
      "pilgrims" who had completed the El Camino without any religious or spiritual
      reason. Therefore this pilgrim route became a long-distance trekking - in the
      point of view of travel medicine. The old age is a high risk for travellers
      moreover in this long distance trekking. Therefore pre-travel counselling would
      be vital for aged pilgrims. Unfortunately, a few articles have been published
      only on the medical problems of El Camino. Taking into consideration the possible
      health damages during the 800 km long "Camino", the author describes its health
      hazards. This study could be a useful guideline for pre-travel advice for El
      Camino pilgrims as only limited information can be gained from the Pilgrims'
      Reception Office (PRO) in Santiago de Compostela. Some information was collected
      from the relevant pages of the internet. Therefore the author could draw limited
      consequences from the statistical data. Yet, the analysis of the medical causes
      of the deceased pilgrims told more about the hazards of 'The Way'. Although the
      number of female and male pilgrims was equal in the statistical data, yet the
      mortality rate of the male pilgrims is much more higher than that of the female
      pilgrims (93-7%). The most frequent cause of death was acute coronary syndrome or
      its suspicion (40-34%). The second most frequent cause of death was road traffic
      accident (17,5-25%). The most vulnerable pilgrims are the cyclists in this
      respect. The exacerbation of any chronic disease was also different among the
      genders (3-25%) but homicide is a more frequent cause of death in the female
      group (2%-8%). The cause of death was exhaustion, stroke, hypothermia and
      drowning (because of the ritual bathing in the sea, after the route completed) as
      well. Orv Hetil. 2018; 159(38): 1535-1542.

PMID- 30227735
TI  - [Effectiveness of trimetazidine prolong in stable coronary artery disease.
      Multicenter, prospective, observational study, ONECAPS study].
AB  - INTRODUCTION: The effectiveness of the manegement of stable coronary artery
      disease among outpatients is not well known. AIM: The aim of the study was to
      evaluate the effect of daily once trimetazidine prolong 80 mg on the angina
      number and severity (Canadian Cardiovascular Society class). METHOD: This
      multicenter, prospective, observational, 3-month clinical study included 2160
      patients, but only 1701 patients completed the study. The patients' mean age was
      68 years (17% under 60 years). The start of angina was 7.8 +/- 6.7 years.
      Hypertension (93.4%) and hypercholesterolemia (81%) were very common. RESULTS:
      The patients were well treated with beta-blocking agents (88%), calcium
      antagonists (49%), angiotensin-converting enzym inhibitors (90%) and statin (77%)
      but only 5% received ivabradine and 50.5% was treated with trimetazidine MR. The
      patients attended 3 visits (inclusion, 1 month, 3 month). During the 3-month
      period, the weekly angina number of all patients treated with trimetazidine
      prolong 80 mg decreased from 2.55 to 0.41 (p<0.0001). A favorable effect was
      observed in CCS grading: CCS I. from 40.37% to 66.81%, CCS II. from 49.89% to
      30.59%, CCS III. from 9.17% to 2% and CCS IV. from 0.56% to 0%. The mean office
      measured blood pressure decreased from 137/83 mmHg to 130/80 mmHg and the heart
      rate from 74 bpm to 71 bpm. CONCLUSIONS: In the real-life, in the stable coronary
      artery disease the angina remains despite the medical treatment. Once a day
      administered trimetazidine prolong 80 mg significantly reduced the weekly number
      of angina and the severity, too. These beneficial effects mediated not only by
      antiischemic effect but also by increased medication adherence. Orv Hetil. 2018;
      159(38): 1549-1555.

PMID- 30227736
TI  - [The differential diagnosis of adverse reactions to non-steroidal anti
      inflammatory drugs. In vitro and in vivo methods].
AB  - INTRODUCTION: According to the present knowledge, the effect of non-steroidal
      anti-inflammatory drugs (NSAIDs) depends on the inhibitory ratio of
      cyclooxigenase (COX)-1 to COX-2 in the plasma membranes. In addition to
      cardiovascular and gastrointestinal side effects, there are adverse symptoms
      which can be divided into cross-intolerance (non-immune mediated) and single or
      multiple hypersensitive (immune mediated) reactions. Due to clinical phenotypes
      and to in vivo aspirin reactivity, adverse effects could be further classified.
      AIM: The aim of these studies was a comparison of hit ratios obtained by a
      humoral serum test measuring specific immunglobulin E (IgE) against a rapid
      cellular test measuring interleukin (IL)-6 release from sensitized mononuclear
      cells due to various suspect NSAID after symptoms within one year. Retrospective
      case studies were performed in in- and out-patients of our teaching hospital in
      Budapest, between 2003 and 2013. METHOD: Specific anti-NSAID IgE levels were
      determined by ELISA in 55 cases. The other matching group of patients consisted
      of 51 patients and 9 tolerant persons. Their separated cells' supernatants were
      checked for IL-6 release incubated for 20 minutes by NSAID dilutions including
      intraassay controls by two-step ELISA assay. Both groups have been stratified
      according to "new" clinical classification. RESULTS: Results have disclosed no
      significant differences among the distribution of clinical symptoms between the
      two groups. In both groups, 9 non-steroidal anti-inflammatory drugs were tested
      representing all frequently used compounds with COX-1 inhibitory potential. The
      overall positivity rate was nearly double (65.4% against 36.9%) within the group
      using IL-6 release assay against that with specific IgE as the diagnostic tool.
      In certain cases, non-drug components of commercial preparations prompted IL-6
      release as well which was paralleled by in vivo test results. Positive in vitro
      tests were obtained in both groups with clinically cross-intolerant as well as
      single or multiple sensitized cases. CONCLUSION: The rates of single or multiple
      sensitized cases exceeded in both groups that of cross-intolerant patients. In
      some phenotypes belonging to the latter categories, IgE type antibodies against
      acetylsalicylic acid could be detected as well. IL-6 release assay was the more
      sensitive test. In addition to pure drugs, other ingredients of medicines could
      also be responsible for adverse events. Orv Hetil. 2018; 159(38): 1556-1566.

PMID- 30227738
TI  - Chitosan-assisted permeabilization of ATP-biotin for live cell kinase-catalyzed
      biotinylation.
AB  - Kinases are essential cell signaling enzymes that phosphorylate protein
      substrates using ATP as the universal cosubstrate. A wide variety of ATP analogs
      have been used in kinase research, although the studies are limited by the cell
      impermeability of ATP. Here we describe the use of the cationic polymer
      deacetylated chitosan to permeabilize ATP analogs for live cell applications,
      including kinase-catalyzed biotinylation.

PMID- 30227737
TI  - [Analysis of the prognostic factors influencing the time elapsing until the
      contralateral hip fracture].
AB  - INTRODUCTION: Although several national studies reported on the risk factors for
      contralateral hip fracture, there are no data about the prognostic factors of the
      time until contralateral hip fractures. AIM: The aim of the study was to analyse
      the impact of different prognostic factors on the time until the development of
      contralateral fracture and to determine the incidence of contralateral hip
      fractures after femoral neck fractures. METHOD: Patients aged 60 years and over
      with contralateral hip fracture between 01 Jan 2000 and 31 Dec 2008 were
      identified among those who suffered their femoral neck fracture in Hungary in
      2000. Risk factors as age, sex, comorbidities, type of fracture and surgery,
      place of living and hospitals providing treatment for primary fracture were
      analysed by one way ANOVA focusing on the time until the development of
      contralateral hip fracture. RESULTS: 312 patients met the inclusion criteria. The
      incidence of contralateral hip fracture after femoral neck fracture ranged
      between 1.5% and 2.1%, the cumulative incidence was 8.24%. The mean time until
      the development of contralateral hip fracture was 1159.8 days. The incidence of
      contralateral hip fracture showed no significant deviation. Significantly shorter
      time (p = 0.010) was detected until the contralateral hip fracture in older
      patients with femoral neck fracture. CONCLUSIONS: The yearly incidence of
      contralateral hip fracture showed no significant difference by patients with
      femoral neck fracture over 60 years. The shorter time until the contralateral hip
      fracture by the older age groups highlights the need of elaboration of prevention
      strategies. Orv Hetil. 2018; 159(38): 1543-1547.

PMID- 30227739
TI  - Synthetic biology: engineering order in organisms across scales and species.
AB  - [Formula: see text] Synthetic biology has enormous potential to solve problems in
      health, agriculture, and energy. Bill Jia and Arin Wongprommoon explore
      engineering approaches to controlling biological processes.

PMID- 30227740
TI  - A useful gene cassette for conditional knock-down of essential genes by targeted
      promoter replacement in Mycobacteria.
AB  - A direct method to study essential genes is to construct conditional knock-down
      mutants by replacement of their native promoter by an inducible one. In
      Mycobacteria, replacement of an essential gene promoter with an
      anhydrotetracycline inducible one was successfully used but required a multi-step
      approach. In this work, we describe a gene cassette for the engineering of a
      conditional knock-down mutant, which allows the one-step targeted replacement of
      mycobacterial promoters by an anhydrotetracycline-inducible promoter. The
      functionality of this cassette was successfully tested by engineering conditional
      clpP and SecA1 mutants of Mycobacterium smegmatis.

PMID- 30227742
TI  - Epitranscriptomics: mapping methods and beyond.
AB  - The field of epigenetics has changed the way we look at both DNA and proteins.
      Could the same be true for RNA? Joseph Martin discusses. [Formula: see text].

PMID- 30227741
TI  - Analysis of rRNA synthesis using quantitative transcription run-on (qTRO) in
      yeast.
AB  - Comparative transcriptional analyses require appropriate and precise
      normalization. Here we describe a modified transcription run-on (TRO) method,
      named quantitative TRO (qTRO), that allows quantification of nascent
      transcription activity. The most critical improvement it introduces is a new
      standardization method for RNA isolation and hybridization steps, enabling
      transcription activity quantification and comparative biological analysis. We
      used this technique with chromatin immunoprecipitation to investigate RNA
      polymerase I (RNAPI) transcription activity and its rDNA gene profiles in
      Saccharomyces cerevisiae. We designed a set of new oligonucleotide probes
      complementary to nascent ribosomal RNA (rRNA) transcripts and standardized their
      hybridization strength. The qTRO method could be successfully implemented to
      study RNAPI transcription in response to oxidative stress and in two mutant
      strains with impaired rRNA synthesis.

PMID- 30227744
TI  - Have you taken a look at our website recently?

PMID- 30227743
TI  - Sequential use of milk and bovine serum albumin for streptavidin-probed western
      blot.

PMID- 30227745
TI  - Simple and cost-effective assay for isolating invasive living cells.
AB  - A modified invasion assay using a three-dimensional collagen gel was developed
      that enables isolation of invasive living cells; it was named the invading cell
      trapping (iCT) assay. A small cell strainer consisting of a nylon mesh with 40
      MUm2 pores was used, and collagen gel layers formed across the membrane. Test
      cells were seeded in the lower gel layer and invasive cells were attracted upward
      and trapped in the upper gel. After incubation, the collagen gel layers in cell
      strainers were easily separated and living cells in the gel were counted and
      analyzed. An advantage of the iCT assay is that it can capture living invasive
      cells in the upper gel while leaving noninvasive ones in the lower layer. Further
      enrichment of the two cell populations can be achieved by repeating the assay.
      Thus, the iCT assay allows comparative analysis of invasive versus noninvasive
      cells.

PMID- 30227747
TI  - Introductory paragraph.

PMID- 30227746
TI  - Proximity ligation assay to study protein-protein interactions of proteins on two
      different cells.
AB  - Protein-protein interactions (PPI) by homo-, hetero- or oligo-merization in the
      cellular environment regulate cellular processes. PPI can be inhibited by
      antibodies, small molecules or peptides, and this inhibition has therapeutic
      value. A recently developed method, the proximity ligation assay (PLA), provides
      detection of PPI in the cellular environment. However, most applications using
      this assay are for proteins expressed in the same cell. We employ PLA for the
      first time to study PPI of cell surface proteins on two different cells.
      Inhibition of PPI using a peptide inhibitor is also quantified using this assay;
      PLA is used to detect PPI of CD2 and CD58 between Jurkat cells (T cells) and
      human fibroblast-like synoviocyte-rheumatoid arthritis cells that are important
      in the immune response in the autoimmune disease rheumatoid arthritis. This assay
      provides direct evidence of inhibition of PPI of two proteins on different cell
      surfaces.

PMID- 30227749
TI  - Gut microbiota modulates drug pharmacokinetics.
AB  - Gut microbiota, one of the determinants of pharmacokinetics, has long been
      underestimated. It is now generally accepted that the gut microbiota plays an
      important role in drug metabolism during enterohepatic circulation either before
      drug absorption or through various microbial enzymatic reactions in the gut. In
      addition, some drugs are metabolized by the intestinal microbiota to specific
      metabolites that cannot be formed in the liver. More importantly, metabolizing
      drugs through the gut microbiota prior to absorption can alter the systemic
      bioavailability of certain drugs. Therefore, understanding intestinal flora
      mediated drug metabolism is critical to interpreting changes in drug
      pharmacokinetics. Here, we summarize the effects of gut microbiota on drug
      pharmacokinetics, and propose that the influence of intestinal flora on
      pharmacokinetics should be organically related to the therapeutic effects and
      side effects of drugs. More importantly, we could rationally perform the strategy
      of intestinal microflora-mediated metabolism to design drugs.

PMID- 30227750
TI  - The evolving role of patient advocates in rare cancers: opportunities and
      challenges.

PMID- 30227748
TI  - The use of biologics and small molecules in pregnant patients with rheumatic
      diseases.
AB  - INTRODUCTION: Biological agents have radically changed the prognosis of rheumatic
      patients. Current evidence demonstrates that tight disease control during
      pregnancy is mandatory to minimize adverse outcome risk. As the new therapeutic
      tools are pivotal to maintain appropriate disease activity, it is timely to
      review available evidence about the safety of biologics and small molecules in
      pregnancy. Areas covered: A comprehensive literature review has been performed,
      reporting available data about the passage into breast milk, rate of pregnancy
      loss and fetal malformations, and long-term complications due to in utero
      exposure to biological agents and small molecules. Expert commentary: Data about
      the safety of agents against tumor necrosis factor in pregnancy are reassuring.
      Even rituximab, tocilizumab, belimumab, ustekinumab, secukinumab, and abatacept
      have not been associated with an increased rate of fetal abnormalities or adverse
      pregnancy outcome. Experience with small molecules is too small to draw any
      conclusion. Even if further data are warranted to define the possible long-term
      effects of in utero biologic exposure on the infant immune system development, it
      is reasonable to speculate that in the next future the use of biologics during
      pregnancy will continue to expand, at least when maternal benefit justifies the
      potential risk to the fetus.

PMID- 30227751
TI  - How safe is pregnancy after liver transplantation? A large case series study at
      tertiary referral center in Turkey.
AB  - OBJECTIVE: To investigate pregnancy outcomes and to define preventative measures
      against to risk factors and complications in pregnancy after liver
      transplantation. Secondary aim is to report postpartum allograft functions in
      these patients. METHOD: This is a case series study. All pregnant women with
      liver transplantations performed in our hospital were enrolled. Patients'
      hospital medical records, electronic records Neonatal Intensive Care Unit (NICU)
      records were used to collect data. Obstetric characteristics and antenatal
      complications, risk factors, pregnancy and neonatal outcomes, all aspects of
      liver transplant variables and allograft functions after pregnancy were studied.
      RESULTS: A total of 11 patients were included in the study. All of them were
      singleton. Mean maternal age was 29.3 +/- 3.9 years. And mean gestational week of
      delivery was 37.2 +/- 2.2. 78% of the women were delivered at term (>37 weeks)
      only two babies were preterm and discharged from NICU without any complications.
      Birth weight (gr median +/- SD) was 2575 +/- 345. Five (45%) patients were
      nulliparous, majority of the cases (8/11, 72%) were conceived of pregnant with
      natural way. Live birth rate was 81% (9/11). Only one patient for each has
      suffered from fetal growth restriction, maternal anemia, maternal
      hyperthyroidism, and ulcerative colitis. Vaginal bleeding was seen in five women
      during the pregnancy. There was no maternal death, stillbirth or neonatal death.
      The mode of delivery for all live birth pregnancies was C-section. And none of
      them was emergency C-section. No complication of allograft function was seen
      after pregnancy. CONCLUSION: Pregnancy in women with liver transplantation is not
      associated with poor pregnancy outcomes and complications for both the mother and
      the neonates when these patients followed up at tertiary referral center with
      multidisciplinary approaches.

PMID- 30227752
TI  - Talking About Hepatitis C: FAQs From Young Adults Who Inject Drugs.
AB  - INTRODUCTION: Young adults who inject drugs and live in rural communities are at
      high risk for hepatitis C virus (HCV) infection. Recent changes in HCV treatment
      must be communicated within these communities to improve access to care and
      reduce HCV transmission. METHODS: Field workers in the !VALE! Hepatitis Treatment
      and Integrated Prevention Services study identified frequently asked questions
      (FAQs) posed by young-adult participants at high risk for HCV during screening
      and educational sessions. From 2016 to 2018, 183 young adults (44.3% women; 85.8%
      Latino/a) younger than 30 years who inject drugs and reside in Rio Arriba or Dona
      Ana counties in New Mexico were enrolled. The research team compiled deidentified
      questions during field enrollments. RESULTS: FAQs were reviewed and categorized
      into four major domains, including risk/prevention, screening, treatment, and
      reinfection. FAQs were addressed by a team of medical and public health
      professionals, using the most current research and recommendations. CONCLUSIONS:
      These FAQs address important gaps in HCV knowledge among young adults who are at
      high risk for infection. The FAQs also highlight the importance of risk reduction
      counseling provided by frontline public health providers as well as access to
      safe and effective HCV treatments for young adults who inject drugs.

PMID- 30227753
TI  - Investigational drugs targeting prostaglandin receptors for the treatment of
      glaucoma.
AB  - INTRODUCTION: Prostaglandin F2alpha analogs were the first prostaglandin agonists
      introduced for glaucoma treatment. Thanks to their efficacy and favorable
      tolerability they set a high bar in competition, with a resultant paucity in new
      hypotensive drug development for many years. However, the scientific community
      has shown recently a new interest in exploring new options for glaucoma
      treatment, generating a remarkable incentive in the marketplace for new drugs.
      Areas covered: This article reviews agents targeting prostaglandin receptors that
      are currently being investigated for glaucoma treatment. We searched published
      literature for agonists targeting all subtypes of prostaglandin receptors found
      in ocular tissues. EP and FP receptor agonists are currently in the spotlight of
      clinical research, while less attention is paid in DP receptor agonists. Expert
      opinion: Prostaglandin analogs, targeting different and combinations of receptor
      subtypes and compounds that exhibit additivity to commonly prescribed medications
      seem to be highly promising options. New treatments need to be safe, more
      effective, superior to existing therapies, tolerable and cost-effective. New
      generation compounds with multiple mechanisms of action or multiagent
      formulations are vigorously being investigated and generated in laboratories
      around the world.

PMID- 30227754
TI  - Mask interface for continuous positive airway pressure therapy: selection and
      design considerations.
AB  - INTRODUCTION: Continuous positive airway pressure (CPAP) therapy is a clinical
      treatment for moderate or severe obstructive sleep apnea (OSA). Commercial CPAP
      mask designs normally come in standard sizes and the configuration is not
      commonly tailored to the patients' characteristics such as face topology, skin
      sensitivity, and severity of OSA syndrome; however, an optimal mask/interface
      selection is a key factor influencing the compliance and effectiveness of CPAP
      treatment. Areas covered: This review investigates the conventional CPAP mask
      design, its effect on OSA treatment, and the related risk factors that can lead
      to skin damage after long-term repeated use. Through a literature search on
      common databases, Scopus, PubMed, and Google Scholar, we identified reported
      facts on the influence of the mask interface and current trends toward customized
      devices. Expert commentary: There is potential for optimizing the CPAP mask fit
      by adapting the interface to the patients' individual characteristics. This holds
      particularly true for users with abnormal features or simply outside conventional
      industry sizing standards. Enabling technologies for undertaking this adaptation
      include reverse engineering, computational modeling, and additive manufacturing.
      There is to date no integrated system that integrates those elements into a
      standard solution, but several studies have shown its effectiveness for specific
      cohorts.

PMID- 30227755
TI  - An Exploration of the Influences Contributing to Food Insecurity in Chester
      County, Pennsylvania.
AB  - Food security refers to the ideal state or condition of households that have
      access at all times to enough food for their members to live an active, healthy
      life. To better understand local food insecurity, a needs assessment was
      implemented to explore contributing factors and discuss solutions. A qualitative
      study including nine focus groups with low-income adults who receive food
      assistance (N = 82) and four focus groups with emergency food providers (N = 21)
      was conducted. Focus group data were analyzed using phenomenological methods.
      Five themes emerged from the residents: (1) food accessibility both contributes
      to and reduces food insecurity; (2) residents understand the need for and
      practice the act of preserving foods; (3) food shopping behaviors were similar
      for the residents and stores were well received; (4) benefits and barriers with
      food insecurity are similar; and (5) variety and quality of food and food safety
      of emergency foods are concerns. The food provider focus groups indicated that
      they recognized similar problems faced by the residents, and they stressed the
      need for education. Food insecure individuals should continue in the
      conversations around solutions, and a comprehensive look at food insecurity
      through local food and health care systems might determine additional needs.

PMID- 30227756
TI  - Using the Awareness, Motivation, Skills, and Opportunity Framework for Health
      Promotion in a Primary Care Network.
AB  - PURPOSE: To use the Awareness, Motivation, Skills, and Opportunity (AMSO)
      framework as a foundation for service delivery in a primary care network (PCN).
      METHOD: The AMSO framework (awareness, motivation, skills, opportunity) was
      integrated into PCN program design: Health Basics (8 weeks with monthly follow
      up) focused on healthy living and Happiness Basics (6 weeks) used positive
      psychology. Evaluation included quality of life (QofL) and participant
      experience; weight, body mass index, and waist circumference were included for
      Health Basics. Data were analyzed using descriptive statistics, paired t tests,
      and thematic analysis. SETTING: PCN in western Canada with midsized urban center
      and surrounding areas. PARTICIPANTS: Health Basics-adults with or at risk for
      chronic disease (n = 103). Happiness Basics-adults with depression, languishing,
      or flourishing (n = 124). RESULTS: Changes were evident in weight loss, body mass
      index, waist circumference, and QofL (p < .05) for Health Basics participants.
      The participants also reported being more active, eating healthier, having a more
      positive mind-set, and having confidence in making lifestyle changes. Happiness
      Basics participants' QofL improved in all domains (p < .05) except the physical
      summary score (p = .079). Happiness participants described positive experiences
      and learned new skills. CONCLUSION: The AMSO framework was successfully
      implemented in our PCN. Recommendations are included to improve program
      effectiveness and use.

PMID- 30227757
TI  - Development of the Mandarin speech banana.
AB  - PURPOSE: For Indo-European languages, "speech banana" is widely used to verify
      the benefits of hearing aids and cochlear implants. As a standardised "Mandarin
      speech banana" is not available, clinicians in China typically use a non-Mandarin
      speech banana. However, as Chinese is logographic and tonal, using a non-Mandarin
      speech banana is inappropriate. This paper was designed to develop the Mandarin
      speech banana according to the Mandarin phonetic properties. METHOD: In the first
      experiment, 14 participants read aloud the standard Mandarin initials and finals.
      For each pronounced sound, its formants were measured. The boundary of all
      formants formed the formant graph (intensity versus frequency). In the second
      experiment, 20 participants listened to a list of pre-recorded initials and
      finals that had been filtered with different bandwidths. The minimum bandwidth to
      recognise a target sound defined its location on the formant graph. RESULT: The
      Mandarin speech banana was generated with recognisable initials and finals on the
      formant graph. Tone affected the shape of the formant graph, especially at low
      frequencies. CONCLUSION: Clinicians can use the new M andarin speech banana to
      counsel patients about what sounds are inaudible to them. Speech training can be
      implemented based on the unheard sounds in the speech banana.

PMID- 30227758
TI  - Development of a novel keratin dressing which accelerates full-thickness skin
      wound healing in diabetic mice: In vitro and in vivo studies.
AB  - Impaired wound healing is a major medical problem in diabetes. The objective of
      this study was to determine the possible application of an insoluble fraction of
      fur-derived keratin biomaterial as a wound dressing in a full thickness surgical
      skin wound model in mice ( n = 20) with iatrogenically induced diabetes. The
      obtained keratin dressing was examined in vitro and in vivo. In vitro study
      showed the keratin dressing is tissue biocompatible and non-toxic for murine
      fibroblasts. Antimicrobial examination revealed the keratin dressing inhibited
      the growth of S. aureus and E. coli. In vivo studies showed the obtained dressing
      significantly ( p < 0.05) accelerated healing during the first week after surgery
      compared to control wounds. Keratin dressings were incorporated naturally into
      granulation and regenerating tissue without any visible signs of inflammatory
      response, which was confirmed by clinical and histopathological analysis. It is
      one of the first studies to show application of insoluble keratin proteins and
      its properties as a wound dressing. The obtained keratin dressing accelerated
      wound healing in mice with iatrogenically induced diabetes. Therefore, it can be
      considered as a safe and efficient wound dressing. Although future studies are
      needed to explain the molecular mechanism behind fur-derived keratin effect
      during the multilayer wound healing process, our findings may open the way for a
      new class of insoluble fur keratin dressings in chronic difficult to heal wounds
      treatment.

PMID- 30227759
TI  - CDK9: a signaling hub for transcriptional control.
AB  - : Cyclin-dependent kinase 9 (CDK9) is critical for RNA Polymerase II (Pol II)
      transcription initiation, elongation, and termination in several key biological
      processes including development, differentiation, and cell fate responses. A
      broad range of diseases are characterized by CDK9 malfunction, illustrating its
      importance in maintaining transcriptional homeostasis in basal- and signal
      regulated conditions. Here we provide a historical recount of CDK9 discovery and
      the current models suggesting CDK9 is a central hub necessary for proper
      execution of different steps in the transcription cycle. Finally, we discuss the
      current therapeutic strategies to treat CDK9 malfunction in several disease
      states. ABBREVIATIONS: CDK: Cyclin-dependent kinase; Pol II: RNA Polymerase II;
      PIC: Pre-initiation Complex; TFIIH: Transcription Factor-II H; snoRNA: small
      nucleolar RNA; CycT: CyclinT1/T2; P-TEFb: Positive Transcription Elongation
      Factor Complex; snRNP: small nuclear ribonucleo-protein; HEXIM: Hexamethylene Bis
      acetamide-inducible Protein 1/2; LARP7: La-related Protein 7; MePCE:
      Methylphosphate Capping Enzyme; HIV: human immunodeficiency virus; TAT: trans
      activator of transcription; TAR: Trans-activation response element; Hsp70: Heat
      Shock Protein 70; Hsp90/Cdc37: Hsp90- Hsp90 co-chaperone Cdc37; DSIF: DRB
      Sensitivity Inducing Factor; NELF: Negative Elongation Factor; CPSF: cleavage and
      polyadenylation-specific factor; CSTF: cleavage-stimulatory factor; eRNA:
      enhancer RNA; BRD4: Bromodomain-containing protein 4; JMJD6: Jumonji C-domain
      containing protein 6; SEC: Super Elongation Complex; ELL: eleven-nineteen Lys
      rich leukemia; ENL: eleven-nineteen leukemia; MLL: mixed lineage leukemia; BEC:
      BRD4-containing Elongation Complex; SEC-L2/L3: SEC-like complexes; KAP1: Kruppel
      associated box-protein 1; KEC: KAP1-7SK Elongation Complex; DRB: Dichloro-1-beta
      D-Ribofuranosylbenzimidazole; H2Bub1: H2B mono-ubiquitination; KM: KM05382; PP1:
      Protein Phosphatase 1; CDK9i: CDK9 inhibitor; SHAPE: Selective 2'-hydroxyl
      acylation analyzed by primer extension; TE: Typical enhancer; SE : Super
      enhancer.

PMID- 30227760
TI  - Establishing a successful rat model of duodenal- jejunal bypass: A detailed
      guide.
AB  - Gastric bypass surgery, an operation that restricts the stomach and bypasses the
      duodenum and part of the jejunum, results in major improvement or remission of
      type 2 diabetes. Duodenual-jejunal bypass was developed by one of the authors
      (FR) as an experimental, stomach-sparing variant of gastric bypass surgery to
      investigate weight-independent mechanisms of surgical control of diabetes.
      Duodenual-jejunal bypass has been shown to improve various aspects of glucose
      homeostasis in rodents and in humans, thus providing an experimental model for
      investigating mechanisms of action of surgery and elusive aspects of
      gastrointestinal physiology. Performing duodenual-jejunal bypass in rodents,
      however, is associated with a steep learning curve. Here we report our experience
      with duodenual-jejunal bypass and provide practical tips for successful surgery
      in rats. Duodenual-jejunal bypass was performed on 50 lean rats as part of a
      study aimed at investigating the effect of the procedure on the physiologic
      mechanisms of glucose homeostasis. During the study, we have progressively
      refined details of anatomic exposure, technical aspects of duodeno-jejunostomy
      and peri-operative care. We analysed the role of such refinements in improving
      operative time and post-operative mortality. We found that refinement of exposure
      methods of the gastro-duodenal junction aimed at minimizing tension on small
      visceral vasculature, technical aspects of duodeno-jejunal anastomosis and peri
      operative management played a major role in improving the survival rate and
      operative time. Overall, an experimental model of duodenual-jejunal bypass was
      successfully reproduced. Based on this experience, we describe here what we
      believe are the most important technical tips to reduce the learning curve for
      the procedure.

PMID- 30227761
TI  - Carfilzomib-based combination regimens are highly effective frontline therapies
      for multiple myeloma and Waldenstrom's macroglobulinemia.
AB  - Multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) are plasma cell
      disorders often treated with proteasome inhibitors. Recently, several studies
      evaluated carfilzomib as an initial treatment for these diseases and reported
      outstanding clinical outcomes. We conducted a retrospective study to report the
      efficacy and safety of frontline carfilzomib-based combinations in a standard of
      care setting. From 2014 until 2016 we identified newly diagnosed MM (n = 54) and
      WM (n = 6) patients treated with carfilzomib as initial therapy who met study
      inclusion criteria. The response rate for myeloma patients was 98% with 77% of
      patients undergoing upfront autologous stem cell transplant. The clinical benefit
      for WM was 100% with all patients having a resolution of B symptoms and anemia
      after treatment. Carfilzomib-based regimens are well tolerated and offer a
      neuropathy sparing approach with excellent responses both in newly diagnosed MM
      and WM making them a good choice for the frontline treatment of these diseases.

PMID- 30227762
TI  - Myelofibrosis patients can develop extramedullary complications including renal
      amyloidosis and sclerosing hematopoietic tumor while otherwise meeting
      traditional measures of ruxolitinib response.

PMID- 30227763
TI  - Breast Tumor Resembling the Tall Cell Variant of Papillary Thyroid Carcinoma:
      Molecular Characterization by Next-Generation Sequencing and Histopathological
      Comparison With Tall Cell Papillary Carcinoma of Thyroid.
AB  - Recent publications have brought attention to the histopathological,
      immunohistochemical, and molecular aspects of the rare breast tumor resembling
      the tall cell variant of papillary thyroid carcinoma (BrTC). Nine archived cases
      of this entity were retrieved, reviewed, and compared with randomly selected tall
      cell variants of papillary thyroid carcinoma (ThTC). Seven of the BrTC cases as
      well as 5 cases of solid papillary carcinoma of breast were analyzed by Oncomine
      next-generation sequencing. BrTC and ThTC were histologically distinguishable by
      the presence of solid architecture, luminal histiocytes, and reverse polarity in
      the former, and psammoma bodies, giant cells, and optically clear nuclei in the
      latter. Sequencing revealed IDH2 R172 single-nucleotide variants in all 7 BrTCs,
      6 of which had concurrent PIK3CA mutations. None of the conventional solid
      papillary carcinomas demonstrated IDH2 mutation. BrTC bears superficial
      resemblance to other papillary tumors but is unique in terms of histology and
      molecular profile.

PMID- 30227764
TI  - The origin of imprinting defects in Temple syndrome and comparison with other
      imprinting disorders.
AB  - Temple syndrome (TS14) is a rare imprinting disorder caused by genetic and
      epigenetic alterations on chromosome 14q32. A subset of these patients shows an
      imprinting defect (ID) where the paternal allele harbors a maternal epigenotype
      thus silencing the paternally expressed genes and leading to an increased
      expression of the maternally expressed genes. We investigated the grandparental
      origin of the incorrectly imprinted chromosome 14 in a cohort of 13 TS14 ID
      patients and their families. In seven families grandmaternal and, in six
      families, grandpaternal inheritance was observed. These results indicate that the
      ID occurred after imprint erasure in the paternal germ line. While the complete
      lack of methylation as observed in the majority of TS14 ID patients may be due to
      an imprint establishment error in the paternal germ line, cases with methylation
      mosaicism suggest that in general many IDs (TS14, AS, BWS, and SRS) are in fact
      of somatic origin in the early or late embryo.

PMID- 30227765
TI  - Treatment Fidelity in Mind-Body Interventions.
AB  - PURPOSE: To contribute to the treatment fidelity literature by providing real
      world examples and suggestion for future research and potential clinical
      application, this article reports on implementation, assessment, and evaluation
      of treatment fidelity in mind-body self-care approaches in at-risk women. METHOD:
      Aligning with best practices, treatment fidelity was integrated into three
      randomized clinical trials. The first examined the effects of a tai chi
      intervention designed to decrease cardiometabolic risk factors in women; the
      second examined the effects of a tailored guided imagery intervention on
      pregnancy outcomes in African American women; and the third explored effects of a
      mindful physical activity intervention (yoga) on psychological outcomes in women
      with moderate to severe depressive symptoms. FINDINGS: Each of the studies
      successfully designed, implemented, and evaluated strategies to address
      recommended treatment fidelity components. These strategies provided qualitative
      and quantitative data that informed intervention refinement, directions for
      future research, and application in clinical practice. CONCLUSIONS: The treatment
      fidelity framework used here is based on best practices and was a feasible and
      reliable approach for ensuring and reporting on treatment fidelity, which is
      contributing to future research to foster translation of potentially effective
      mind-body self-care approaches into practice.

PMID- 30227767
TI  - Does left ventricular hypertrophy by electrocardiogram predict adverse outcomes
      in pregnancies with chronic hypertension?
AB  - OBJECTIVES: The American College of Obstetricians and Gynecologists Task Force on
      Hypertension in Pregnancy recommends assessing left ventricular function with
      echocardiogram or electrocardiogram (ECG) in women with severe hypertension of
      long duration. We aim to compare the rates of superimposed preeclampsia (SIP) and
      other obstetrical outcomes in pregnancies with chronic hypertension (CHTN) and
      left ventricular hypertrophy (LVH) by ECG criteria with mothers without LVH.
      STUDY DESIGN: After IRB approval, we performed a retrospective chart review from
      January 2015 to December 2016. Singleton pregnancies with CHTN who carried the
      pregnancy beyond 20 weeks and planned to deliver at our institution were included
      for analysis. Patients with insufficient data, multiple gestations, and those
      with systemic lupus erythematosus were excluded from this study. Rates of SIP and
      other obstetrical outcomes were compared among those with LVH and those without
      LVH. Univariate parametric and nonparametric statistical models were applied as
      appropriate. Associations were considered statistically significant at an alpha
      level of 0.05. RESULTS: We included 218 pregnancies. Nineteen (8.7%) had LVH. The
      rate of SIP was higher in pregnancies with LVH than in those without it (68
      versus 41%; OR = 3.01; 95% CI 1.1-8.5; p = .022). The birthweight was lower in
      the LVH group (2432 g [2120-2990] versus 2870 g [2430-3440]; p = .016). Other
      obstetrical outcomes were not significantly different between those patients with
      LVH and those without. CONCLUSIONS: LVH by ECG criteria may be associated with
      higher rates of SIP and with lower birthweight in pregnancies with CHTN. ECG may
      be a cost-effective tool to identify patients with CHTN at risk of adverse
      outcomes. Larger trials are necessary to corroborate our findings.

PMID- 30227766
TI  - Ivory arthroplasty for trapeziometacarpal osteoarthritis: 10-year follow-up.
AB  - : This prospective study investigates long-term functional outcome after total
      trapeziometacarpal joint replacement with the Ivory arthroplasty for
      trapeziometacarpal joint osteoarthritis. Clinical outcome, overall function,
      pain, and radiologic outcome after a minimum of 10 years were evaluated for 26
      Ivory arthroplasty in 24 patients. Two patients had bilateral arthroplasties. The
      female to male ratio was 22:2, and the mean age was 71 years (range 57-83). The
      mean follow-up period was 130 months (range 120-142). Overall functioning as
      defined by the QuickDASH score and visual analogue pain score improved by 50% and
      81%, respectively, when compared with the preoperative status. However, these
      outcomes deteriorated beyond 5 years after surgery. Long-term results suggest the
      Ivory arthroplasty to be a reliable treatment for trapeziometacarpal
      osteoarthritis since it improves overall function and reduces pain up to 10 years
      postoperatively. However, revision within 10 years after surgery was needed in
      four of 26 cases. LEVEL OF EVIDENCE: II.

PMID- 30227768
TI  - "I Would Like to Be Heard." Communicating With Singaporean Chinese Patients With
      Dementia: A Focused Ethnography Study.
AB  - INTRODUCTION: Although first-generation Singaporean Chinese were mainly
      immigrants from Mainland China, the communication patterns of Singaporean Chinese
      in the present-day context differs from Mainland Chinese. This difference could
      be attributed to the subculture but is not conclusive. This study aimed to
      explore the experiences of nursing staff communicating with Singaporean Chinese
      with dementia in Singapore. METHOD: A focused ethnographic study was conducted in
      a long-term care setting for people with dementia, where data were obtained using
      nonparticipant observations and semistructured interviews. Data analyses were
      conducted using Braun and Clarke's thematic analysis. RESULTS: Nineteen nursing
      staff were interviewed. The central theme of "embracing diversity and accepting
      differences" was supported by three subthemes: acknowledging cultural
      differences, understanding the patients, and overcoming communicative challenges.
      CONCLUSIONS: This study highlighted the need for nurses to understand cultural
      characteristics among Singaporean Chinese with dementia especially on emotional
      expressions when they are not understood by others.

PMID- 30227770
TI  - Minor contribution of CYP3A5 to the metabolism of hepatitis C protease inhibitor
      paritaprevir in vitro.
AB  - Paritaprevir (PTV) is a non-structural protein 3/4A protease inhibitor developed
      for the treatment of hepatitis C disease as a fixed dose combination of
      ombitasvir (OBV) and ritonavir (RTV) with or without dasabuvir. The aim of this
      study was to evaluate the effects of cytochrome P450 (CYP) 3A5 on in vitro PTV
      metabolism using human recombinant CYP3A4, CYP3A5 (rCYP3A4, rCYP3A5) and human
      liver microsomes (HLMs) genotyped as either CYP3A5*1/*1, CYP3A5*1/*3 or
      CYP3A5*3/*3. The intrinsic clearance (CLint, Vmax/Km) for the production of a
      metabolite from PTV in rCYP3A4 was 1.5 times higher than that in rCYP3A5. The PTV
      metabolism in CYP3A5*1/*1 and CYP3A5*1/*3 HLMs expressing CYP3A5 was comparable
      to that in CYP3A5*3/*3 HLMs, which lack CYP3A5. CYP3A4 expression level was
      significantly correlated with PTV disappearance rate and metabolite formation. In
      contrast, there was no such correlation found for CYP3A5 expression level. This
      study represents that the major CYP isoform involved in PTV metabolism is CYP3A4,
      with CYP3A5 having a minor role in PTV metabolism. The findings of the present
      study may provide foundational information on PTV metabolism, and may further
      support dosing practices in HCV-infected patients prescribed PTV-based therapy.

PMID- 30227769
TI  - Impact of preoperative elevated serum creatinine on long-term outcome of patients
      undergoing aortic repair with Stanford A dissection: a retrospective matched pair
      analysis.
AB  - BACKGROUND: The aim of the present study was to determine whether raised
      preoperative serum creatinine affected the long-term outcome in patients
      undergoing surgical aortic repair for Stanford A acute aortic dissection (AAD).
      METHODS: A total of 240 patients diagnosed with Stanford A AAD underwent surgical
      repair from January 2006 to April 2015. A propensity score matching was applied,
      resulting in 73 pairs consisting of one group with normal and one group with
      preoperative elevated creatinine levels. The cohorts were well balanced for
      baseline and preoperative clinical characteristics. Both groups were compared
      regarding their early postoperative variables, as well as estimated survival with
      up to 9-year follow up. Also, the impact of acute postoperative kidney injury and
      its severity on long-term survival was analyzed. RESULTS: The proportion of
      patients suffering Stanford A AAD with raised creatinine levels was 31.3% ( n =
      75). After propensity matching, there were no statistically significant
      differences regarding demographics, comorbidities, preoperative baseline and
      clinical characteristics. Postoperatively matched patients with elevated
      creatinine had longer intensive care unit ( p < 0.001) and total hospital stay (
      p = 0.002), prolonged intubation times ( p = 0.014), higher need for
      hemofiltration ( p < 0.001), higher incidence of temporary neurological disorders
      ( p = 0.16), infection ( p = 0.005), and trend toward higher incidence of sepsis
      ( p = 0.097). However, there were no significant differences regarding 30-day
      mortality (20.5% versus 20.5%, p = 1.000) and long-term overall survival.
      Further, neither the incidence nor the different stages of acute kidney injury
      according to the Acute Kidney Injury Network showed any statistically significant
      differences in terms of long-term survival for both groups [log rank p = 0.636,
      Breslow (generalized Wilcoxon) p = 0.470, Tarone-Ware p = 0.558]. CONCLUSIONS:
      Patients with elevated creatinine levels undergoing surgical repair for Stanford
      A AAD demonstrate higher rate of early postoperative complications. However, 30
      day mortality and long-term survival in this patient cohort is not significantly
      impaired.

PMID- 30227771
TI  - Trends in the Conferral of Graduate Public Health Degrees: A Triangulated
      Approach.

PMID- 30227772
TI  - Multicentre, randomised, blinded, control trial of drug-eluting balloon vs Sham
      in recurrent native dialysis fistula stenoses.
AB  - BACKGROUND: Endovascular treatment of autogenous arteriovenous haemodialysis
      fistula stenosis has high reintervention rates. We investigate the effect of drug
      eluting balloons in the treatment of recurrent haemodialysis fistula stenosis.
      METHODS: This is a randomised, controlled, investigator-initiated and run,
      prospective, blinded, multicentre trial. Patients with recurrent autogenous
      arteriovenous haemodialysis fistula stenosis received standard endovascular
      treatment plus drug-eluting balloon or standard endovascular treatment plus
      uncoated balloon (Sham). Primary endpoint was late lumen loss in trial area on
      ultrasound at 6 weeks, 3, 6 and 12 months. Secondary endpoints were freedom from
      reintervention to the Index Trial Area and decline in fistula flow (Qa). Interim
      analysis was performed at 6 months (unblinded due to timeliness). RESULTS:
      Patients with 132 recurrent stenoses (48% in bare Nitinol stents) were randomised
      with 70 receiving drug-eluting balloon and 62 Sham. At 6 months, decline in late
      lumen loss was 0.23 +/- 0.03 mm/month for Sham and 0.045 +/- 0.03 mm/month for
      drug-eluting balloon arm, a significant difference (0.18 mm, p = 0.0002). At 12
      months, this difference persisted at 0.12 mm (p = 0.0003). At 6 months,
      significant difference in late lumen loss for instent restenoses (p = 0.0004) was
      observed, with non-significant difference for unstented restenoses (p = 0.065).
      Mean time for freedom from reintervention was 10.14 months for Sham versus 42.39
      months for drug-eluting balloon (p = 0.001). The same was shown for instent (p =
      0.014) and unstented (p = 0.029) restenoses. Qa decline rate at 6 months was
      36.89 mL/min/month (Sham) and 0.41 mL/min (drug-eluting balloon). The difference
      was significant (36.48 mL/min; p = 0.02) and persisted to 12 months (p = 0.44).
      CONCLUSION: Paclitaxel drug-eluting balloon significantly delays restenosis after
      angioplasty for recurrent autogenous arteriovenous haemodialysis fistula
      stenosis, persisting to 12 months. Drug-eluting balloon significantly increases
      freedom from reintervention at 12 months with these effects true in stented and
      unstented fistulas.

PMID- 30227773
TI  - A World of Blame to Go Around: Cross-Cultural Determinants of Responsibility and
      Punishment Judgments.
AB  - Research finds collectivists make external attributions for others' behavior,
      whereas individualists make internal attributions. By focusing on external
      causes, collectivists should be less punitive toward those who harm others. Yet,
      many collectivistic cultures are known for strict retributive justice systems.
      How can collectivists simultaneously make external attributions and punish so
      harshly? We hypothesized that unlike individualists whose analytic tendencies
      engender a focus on mental states where judgments of accountability stem from
      perceptions of a harm-doer's agency, collectivists' holistic cognitive tendencies
      engender a focus on social harmony where judgments of accountability stem from
      perceived social consequences of the harmful act. Thus, what leads collectivists
      to make external attributions for behavior also leads to harsh punishment of
      those harming the collective welfare. Four cross-cultural studies found evidence
      that perceptions of a target's agency more strongly predicted responsibility and
      punishment judgments for individualists, whereas perceived severity of the harm
      was stronger for collectivists.

PMID- 30227774
TI  - Percutaneous Cholecystostomy for Severe Acute Cholecystitis: A Useful Procedure
      in High-Risk Patients for Surgery.
AB  - BACKGROUND: Acute cholecystitis has the potential to cause sepsis and death,
      particularly in patients with poor physiological reserve. The gold standard
      treatment of acute cholecystitis (cholecystectomy) is often not safe in high-risk
      patients and recourse is made to percutaneous cholecystostomy as either definite
      treatment or temporizing measure. The aim of this study is to evaluate early and
      late outcomes following percutaneous cholecystostomy in patients with acute
      cholecystitis treated at our institution. METHODS: All patients who underwent
      percutaneous cholecystostomy for acute cholecystitis (excluding patients with
      malignancy) between January 2005 and September 2014 were included in the study.
      RESULTS: A total of 53 patients (22 female, median age, 74 years; range, 27-95
      years) underwent percutaneous cholecystostomy during the study period. In total,
      12 patients (22.6%) had acalculous cholecystitis. The main indications for
      percutaneous cholecystostomy were significant co-morbidities (n = 28, 52.8%) and
      patients too unstable for surgery (n = 21, 39.6%). The median time to
      percutaneous cholecystostomy from diagnosis of acute cholecystitis was 3.6 days
      (range, 0-45 days). The median length of hospital stay was 27 (range, 4-87) days.
      The overall 90-day mortality was 9.3% with two further deaths at 12-month follow
      up. The mortality was significantly higher in patients with American Society of
      Anesthesiology grade 4-5 (18% vs 0% in American Society of Anesthesiology grade 2
      3, p = 0.026) and in patients with acalculous cholecystitis (25% vs 4.5%, p =
      0.035). The overall readmission rate was 18%. A total of 24 (45.2%) patients had
      surgery: laparoscopic cholecystectomy, n = 11; laparoscopic converted to open, n
      = 5; open total cholecystectomy, n = 5; open cholecystectomy, n = 1; laparotomy
      and washout, n = 1; laparotomy partial cholecystectomy and closure of perforated
      small intestine and gastrostomy, n = 1. CONCLUSION: Percutaneous cholecystostomy
      is a useful temporary or permanent procedure in patients with acute cholecystitis
      of both calculous and acalculous origin, who are unfit for surgery.

PMID- 30227775
TI  - Stepwise oral immunotherapy for 10 days in an egg-white allergy mouse model did
      not ameliorate the severity of allergy but induced the production of allergen
      specific IgA.
AB  - We examined whether the stepwise oral immunotherapy (OIT) for 10 days ameliorates
      the severity of allergy and the biomarkers in an allergy mouse model. The OIT
      could not protect anaphylaxis symptoms after allergen challenges but promote the
      production of antibodies, especially allergen-specific IgA. It was suggested that
      this OIT influenced the function of immuno response against the allergen.
      Abbreviations: EW: egg white; IFC: intraperitoneal food challenge; IFN-gamma:
      interferon-gamma; IL: interleukin; OVA: ovalbumin; OM: ovomucoid; OFC: oral food
      challenge; OIT: oral immunotherapy.

PMID- 30227776
TI  - Neuroprotective effect of Capsicum annuum var. abbreviatum against hydrogen
      peroxide-induced oxidative stress in HT22 hippocampus cells.
AB  - Phenolic compounds isolated from pepper (Capsicum annum) have been demonstrated
      to have neuroprotective effects, whereas the physiological properties of Capsicum
      annuum var. abbreviatum (CAA) have not been studied. Thus, we investigate the
      chemical composition and neuroprotective activity of CAA extract (CAAE) in HT22
      hippocampus cells against H2O2-induced neurotoxicity. CAAE treatment resulted in
      a significant protection of H2O2-exposed HT22, this protection ultimately
      occurred through an inhibition of MDA and ROS levels and an induction of SOD
      activity. Furthermore, CAAE treatment reduced H202-induced apoptosis though
      decreasing the expression of pro-apoptotic factors (Bax, cytochrome c, and
      cleaved caspases-3) while increasing the expression of the anti-apoptotic factors
      (Bcl-2), as well as the accumulation of nucleus-Nrf2-mediated HO-1 signaling.
      Interestingly, CAAE has a high concentration of unique phenolic compositions
      (chlrogenic acid, tangeretin, etc.) than other capsicum annum extracts.
      Altogether, these findings suggest that CAAE can be a useful natural resource for
      alleviating neurodegenerative diseases.

PMID- 30227777
TI  - Perceived Health Status in Rural Manufacturing Workers.
AB  - Manufacturing workers comprise 8.8% of the total U.S. workforce representing a
      sizable population for disease prevention and health promotion by occupational
      health nurses within worksite wellness programs. The purpose of this study was to
      examine the relationship between perceived health status and objective health
      status including existing chronic disease among rural manufacturing workers.
      Rural manufacturing workers ( n = 114) completed a general health survey and
      consented to a retrospective chart review. All were participants in a direct
      incentive wellness program with biometric data available. The majority of
      participants were males between the ages of 46 and 60 years, and nearly half of
      the sample had a college degree. A statistically significant difference was
      observed between number of chronic diseases and lower perceived health status.
      These findings have implications for occupational health nurses and other health
      care providers to identify workers at risk for chronic illness through self
      perceived health status assessment.

PMID- 30227778
TI  - Cytogenetic alterations induced by flupyradifurone, a new butenolide insecticide,
      in human lymphocytes.
AB  - Flupyradifurone (FPD), a member of the new class of butenolide insecticides, acts
      on nicotinic acetylcholine receptors. Studies on genotoxic and carcinogenic
      effects of FPD are very limited. This is the first study to investigate the
      cytotoxic and genotoxic effects of FPD and its metabolites on human lymphocyte
      cultures with or without a metabolic activation system (S9 mix) using chromosomal
      aberration (CA) and micronucleus (MN) tests. The cultures were treated with 85,
      170, and 340 ug/ml of FPD in the presence (3 h treatment) and absence (48 h
      treatment) of S9 mix. Dimethyl sulfoxide (DMSO) was used as a solvent control.
      Statistically significant decreases were detected at the medium and highest
      concentrations for 48 h treatments while decreases in mitotic index (MI) in the
      presence of the S9 mix were found statistically significant at all FPD
      concentrations tested when compared with the solvent control. FPD also decreased
      the nuclear division index (NDI) at the highest concentration (340 ug/ml) in the
      absence of S9 mix. When compared with the solvent control, increases in CA
      frequencies were significant at the medium and highest concentrations.
      Significantly increased MN frequency was only found at the highest FPD
      concentration in cultures without S9 mix compared with the solvent control while
      increases in the MN frequencies in the presence of S9 mix were statistically
      significant at all FPD concentrations. The results of the present study indicate
      that FPD and its metabolites can show cytotoxic and genotoxic effects in human
      lymphocytes. More genotoxicity studies are necessary to make a possible risk
      assessment in humans.

PMID- 30227779
TI  - Synthesis, characterization, and pharmacological evaluation of zinc oxide
      nanoparticles formulation.
AB  - Zinc oxide nanoparticles (ZnONPs) are being used extensively in manufacturing
      skin lotions and food products and in various biological and pharmaceutical
      industries because of their immunomodulatory and antimicrobial properties. In
      this study, ZnONPs were synthesized by a precipitation method and characterized
      by X-ray diffraction (XRD) techniques, scanning electron microscopy (SEM), and
      ultraviolet-visible spectroscopy to investigate their structural, morphological,
      and optical properties. For in vivo evaluation, 40 healthy albino mice were
      randomly allocated to four equal groups among which the first one was the control
      group, while the second, third, and fourth were treated with carbon tetrachloride
      (CCl4), a blend of CCl4 and ZnONPs, and ZnONPs alone, respectively, for 21 days.
      The XRD analysis confirmed hexagonal wurtzite type structures having an average
      crystallite size of 41.54 nm. The morphology of ZnONPs analyzed through SEM
      showed uniform distribution of the grains and shape of the synthesized oxide. The
      energy band gap of the ZnONPs was found to be 3.498 eV. Hepatic and renal damage
      following CCl4 administration was apparent after 14 days and was increased at the
      21st day, showing nodular fibrotic masses in the liver and bumpy surfaces in the
      kidney as observed by gross and histological examination. Coadministration of
      ZnONPs (15 mg/kg b.w. intragastrically 5 days a week) significantly prevented the
      CCl4-dependent increases in alanine transaminase, aspartate transaminase,
      creatinine, and urea levels, suggesting a protective potential of ZnONPs.

PMID- 30227780
TI  - 1-stage bilateral total hip arthroplasty operation in 22 patients with use of
      short and standard stem length on either side: gait analysis 1 and 2 years after
      bilateral THA.
AB  - BACKGROUND: According to previous gait analyses, insertion of a total hip
      arthroplasty (THA) will improve the range of hip flexion-extension but not to
      normal. Use of short stems could have a potential to improve the motion by
      preservation of more bone and muscular attachments. We evaluated whether a short
      femoral stem resulted in improved hip motion compared to a conventional stem in
      patients who underwent 1-stage bilateral THA. The most painful hip was randomised
      to either design and the 2nd hip was operated with the design not used on the 1st
      side. METHODS: Gait analysis was performed with an optical tracking system in 22
      patients. The follow-up was performed 1 and 2 years after the operation. The mean
      age was 59 (SD 7.7) years and body mass index was 27.7 (SD 4.3). 66 subjects
      without hip pathology served as controls. RESULTS: Minimal differences were
      observed, between or within the 2 different stem designs during gait at the 2
      follow-up occasions. Comparison between each of the 2 stem designs and controls
      at 2 years revealed reduced stride length (p = 0.009), cadence, hip extension
      (p<0.001) and hip extension-flexion range (p = 0.021) for both designs.
      Furthermore, the range of hip adduction-abduction (p = 0.046) and hip abduction
      moment for both designs in the frontal plane was also reduced bilaterally
      (p<0.001). CONCLUSIONS: We found no difference in gait parameters between the
      short and the conventional stem after 1-stage bilateral THA. Although both hip
      joints were operated at the same time motions and moments did not normalise after
      bilateral 1-stage operations.

PMID- 30227781
TI  - An evaluation of off-axis manual forces and upper extremity joint moments during
      unilateral pushing and pulling exertions.
AB  - This study quantified changes in off-axis manual force production and upper
      extremity joint moments during sub-maximal one-handed push and pull tasks. Off
      axis forces in the up/down and left/right directions were quantified in the
      presence or absence of constraints placed upon the direction of manual force
      application and/or arm posture. Resultant off-axis forces of 13.1% and 9.4% were
      produced for pulls and pushes, respectively. Off-axis forces during pulling were
      oriented downwards and to the right, and were associated with a decreased should
      flexion moment when posture was constrained. Off-axis forces in the up/down
      direction were minimized with increased on-axis force level. Off-axis forces
      during pushing tended to be oriented to the left and were associated with
      increased elbow flexion moment when off-axis forces were allowed. By not
      accounting for these off-axis forces, we may not be accurately reflecting
      actionable muscle- and joint-level loading characteristics derived from
      biomechanically-based proactive ergonomics assessment approaches. Practitioner
      Summary: Constrained arm postures and directions of manual force application
      influence the production of off-axis forces. As inaccurate estimation of true
      manual forces can markedly influence actionable outcomes of proactive ergonomic
      assessments, this study suggests that simplification of these estimates is
      insufficient and potentially misleading.

PMID- 30227782
TI  - Endovascular stent placement for isolated superior mesenteric artery dissection
      with intestinal ischaemia.
AB  - BACKGROUND: Isolated superior mesenteric artery dissection (ISMAD) is rare,
      especially when associated with intestinal ischaemia. We report our clinical
      experience managing this condition. PATIENTS AND METHODS: Medical records from 22
      patients with ISMAD and intestinal ischaemia were retrospectively analysed.
      Conservative treatment was given to all patients as first line therapy.
      Subsequently, 15 patients received endovascular stent placement and three
      patients received endovascular stent placement plus intestinal resection and
      anastomosis. RESULTS: After conservative treatment, the symptoms of three
      patients were remarkably relieved; however, a repeat contrast CT showed that
      stenosis was aggravated. Hence, endovascular stent placement was performed in all
      15 patients. Enteral nutrition was successfully restored in 12 patients. Three
      patients showed signs of chronic intestinal ischaemia, including peritonitis and
      ileus. These patients underwent intestinal resection and anastomosis. Enteral
      nutrition was restored at postoperative week two. No signs of intestinal
      ischaemia recurred during two-years of follow-up. CONCLUSIONS: We recommend
      endovascular stent placement as a feasible, effective, and minimally invasive
      procedure in patients with ISMAD and symptoms of intestinal ischaemia.

PMID- 30227784
TI  - A device to make the pelvic sagittal plane horizontal and reduce error in cup
      inclination during total hip arthroplasty: a validation study.
AB  - INTRODUCTION: Radiological inclination (RI) is determined in part by operative
      inclination (OI), which is defined as the angle between the cup axis or handle
      and the sagittal plane. In lateral decubitus the theatre floor becomes a
      surrogate for the pelvic sagittal plane. Critically at the time of cup insertion
      if the pelvic sagittal plane is not parallel to the floor either because the
      upper hemi pelvis is internally rotated or adducted, RI can be much greater than
      expected. We have developed a simple Pelvic Orientation Device (POD) to help
      achieve a horizontal pelvic sagittal plane. METHODS: A model representing the
      posterior aspect of the pelvis was created. This permitted known movement in 2
      planes to simulate internal rotation and adduction of the upper hemi pelvis, with
      15 known pre-set positions. 20 participants tested the POD in 5 random, blinded
      position combinations, providing 200 readings. The accuracy was measured by
      subtracting each reading from the known value. RESULTS: Two statistical outliers
      were identified and removed from analysis. The mean adduction error was 0.73
      degrees . For internal rotation, the mean error was -0.03 degrees . Accuracy
      within 2.0 degrees  was achieved in 176 of 190 (93%) of readings. The maximum
      error was 3.6 degrees  for internal rotation and 3.1 degrees  for adduction.
      CONCLUSION: In a model pelvis the POD provided an accurate and reproducible
      method of achieving a horizontal sagittal plane. Applied clinically, this simple
      tool has the potential to reduce the high values of RI sometimes seen following
      THA in lateral decubitus.

PMID- 30227783
TI  - Observational Study Design in Veterinary Pathology, Part 2: Methodology.
AB  - Observational studies are a basis for much of our knowledge of veterinary
      pathology, yet considerations for conducting pathology-based observational
      studies are not readily available. In part 1 of this series, we offered advice on
      planning and carrying out an observational study. Part 2 of the series focuses on
      methodology. Our general recommendations are to consider using already-validated
      methods, published guidelines, data from primary sources, and quantitative
      analyses. We discuss 3 common methods in pathology research-histopathologic
      scoring, immunohistochemistry, and polymerase chain reaction-to illustrate
      principles of method validation. Some aspects of quality control include use of
      clear objective grading criteria, validation of key reagents, assessing sample
      quality, determining specificity and sensitivity, use of technical and biologic
      negative and positive controls, blinding of investigators, approaches to
      minimizing operator-dependent variation, measuring technical variation, and
      consistency in analysis of the different study groups. We close by discussing
      approaches to increasing the rigor of observational studies by corroborating
      results with complementary methods, using sufficiently large numbers of study
      subjects, consideration of the data in light of similar published studies,
      replicating the results in a second study population, and critical analysis of
      the study findings.

PMID- 30227785
TI  - The Unmet Needs of Patients With Progressive Neurological Diseases in the Czech
      Republic: A Qualitative Study.
AB  - AIM: The aim of our research was to explore the unfulfilled needs of patients
      with a progressive neurological disease in advanced stage of the illness within
      the current system of health and social care in the Czech Republic. DESIGN AND
      SETTING: Qualitative research (grounded theory) was used to conceptualize the
      patterns of unmet palliative care needs in Czech Republic. METHODS: The data
      collection method comprised individual, in-depth interviews (n = 19) and focus
      groups (n = 4) where a total of 52 respondents participated (patients with
      progressive neurological diseases [PNDs], family members, and professionals).
      RESULTS: Two main categories of unfulfilled needs were determined (life with the
      disease, professional help), and they were described in the context of the 3
      crucial themes identified in the study-the symptoms of the advanced stage of the
      disease resulted in substantial reduction of physical self-sufficiency, loss of
      autonomy, and social isolation; the level of dependence on the support and help
      of others increased; the patients also highlighted several problems related to
      health-care services. CONCLUSION: The unmet needs should be taken into
      consideration when creating the concept of the neuropalliative and rehabilitation
      care, including the mental health support plan, because of the emotional,
      behavioral, and cognitive disorders that frequently occur in the lives of a
      substantial amount of patients with PND.

PMID- 30227786
TI  - Bypassing the gatekeeper: incidental negative cues stimulate choices with
      negative outcomes.
AB  - The Theory of Event Coding (TEC) predicts that exposure to affective cues can
      automatically trigger affectively congruent behaviour due to shared
      representational codes. An intriguing hypothesis from this theory is that
      exposure to aversive cues can automatically trigger actions that have previously
      been learned to result in aversive outcomes. Previous work has indeed found such
      a compatibility effect on reaction times in forced-choice tasks, but not for
      action selection in free-choice tasks. Failure to observe this compatibility
      effect for aversive cues in free choice tasks suggests that control processes
      aimed at directing behaviour toward positive outcomes may overrule the automatic
      activation of affectively congruent responses in case of aversive cues. The
      present study tested whether minimising such control could cause selection of
      actions that have been learned to result in aversive outcomes. Results showed
      incidental exposure to aversive cues biased selection of behaviours with learned
      aversive outcomes over behaviours with positive outcomes, despite a preference to
      execute the positive- over the negative-outcome actions evidenced by a separate
      behaviour measurement and self-reports. These results suggest motivational
      processes to select actions with positive consequences may sometimes be bypassed.
      Data and Materials: http://doi.org/10.17605/osf.io/ym7qu.

PMID- 30227787
TI  - Editor's Letter.

PMID- 30227788
TI  - Journal of Correctional Health Care.

PMID- 30227789
TI  - Preliminary report of a new type of braided vein stent in animals.
AB  - Background Iliofemoral vein stenosis or occlusion is a common cause of severe
      chronic venous insufficiency. Endovascular venous stenting has become a preferred
      treatment because it is minimally invasive and has a high safety profile. Despite
      the wide application of the wallstent, it is not specifically designed for veins.
      There are currently few studies on braided stents in the field of veins. We
      designed a novel braided vein stent, which has higher radial resistive force and
      more optimized looped ends structure compared with the wallstent. The purpose of
      this study was to evaluate the safety and performance of the stent in animals,
      providing a reference for further clinical trials. Methods The Wallstent is used
      as a control group. The novel stent and the Wallstent were implanted in the iliac
      vein of sheep. After 30 days and 90 days, vascular injury, thrombus, neointima
      coverage, and luminal stenosis were evaluated through venous angiography,
      endoscopic observation of stent specimen and histopathology. Imaging, histology,
      and integration data were analyzed by t-test for comparisons between the groups.
      Results Two groups of stents were successfully implanted. Follow-up observation
      showed that there was no thrombosis or obstruction >50% occurred in any group and
      no significant differences in patency, vascular injury, or intimal hyperplasia
      compared with the Wallstent. Conclusion The novel stent significantly increases
      the radial resistive force and does not increase vascular injury, thrombus and
      stent stenosis during 30-day and 90-day follow-up. The next step is to further
      validate the effectiveness of the stent through long-term animal observation and
      human clinical trials.

PMID- 30227790
TI  - A practical approach to tumescent local anaesthesia in ambulatory endovenous
      thermal ablation.
AB  - Background Thermal ablation, usually performed with tumescent local anaesthesia
      (TLA), is the preferred method for varicose veins treatment. Tumescent local
      anaesthesia is always cited; however, little detail of the procedure is presented
      in publications. This retrospective audit of clinical tumescent local anaesthesia
      practice aims to provide detailed information on an important aspect of
      endovenous practice. Methods Patients who underwent three types of endothermal
      treatment (Venefit, Radiofrequency Induce Thermal Therapy and Endovenous Laser
      Ablation) to a single saphenous trunk using tumescent local anaesthesia were
      assessed. Differences in tumescent local anaesthesia volume per unit length of
      treated vein were assessed for the followings: type of saphenous trunk, length of
      vein treated, effect of additional phlebectomy and bilateral versus interval
      unilateral treatment for bilateral veins. Descriptive data are reported as mean
      and standard deviation, and groups were compared using the one-way ANOVA test.
      Results Between 2008 and 2014, single-saphenous-trunk ambulatory TLA thermal
      ablation was performed in 979 patients, mean age was 54 years. A total of 1229
      limbs had truncal ablations and synchronous phlebectomy was performed in 470
      limbs. No tumescent local anaesthesia-related complications occurred. There was
      no significant difference in standardised tumescent local anaesthesia volume per
      centimetre (ml) used for the three devices. Tumescent local anaesthesia volume
      per centimetre (ml) differed significantly between saphenous trunks. On average,
      a standard 10-12 ml/cm of tumescent local anaesthesia was used for saphenous
      trunks. Mean total tumescent local anaesthesia volume per patient, when treating
      the great saphenous vein alone, was 931 ml for bilateral and 425 ml for
      unilateral treatment. Conclusion This report of over 1000 endovenous procedures
      demonstrates safe performance of laser and radiofrequency treatments using
      tumescent local anaesthesia. Although no attempt was made to determine minimum
      volume requirements, a mean tumescent local anaesthesia volume of 10-12 ml/cm
      administered to the perivenous space provides adequate anaesthesia for truncal
      saphenous ablation.

PMID- 30227791
TI  - Need for adjunctive procedures following cyanoacrylate closure of incompetent
      great, small and accessory saphenous veins without the use of postprocedure
      compression: Three-month data from a postmarket evaluation of the VenaSeal System
      (the WAVES Study).
AB  - Purpose Studies examining cyanoacrylate closure of saphenous veins with the
      VenaSealTM System have not allowed concomitant procedures for tributaries at the
      time of the index procedure. Outside of clinical trials, however, concomitant
      procedures are frequently performed in conjunction with endovenous ablation. We
      report on the frequency of need for saphenous tributary treatment three months
      after cyanoacrylate closure of the treatment of great saphenous vein, small
      saphenous vein, and/or accessory saphenous vein. Methods Fifty subjects with
      symptomatic great saphenous vein, small saphenous vein, and/or accessory
      saphenous vein incompetence were treated with no postprocedure compression
      stockings. Concomitant procedures were not allowed. Treating physicians predicted
      the type and nature of any concomitant procedures that they would usually perform
      at the time of ablation, if not limited by the constraints of the study.
      Evaluations were performed at one week, one and three months and included duplex
      ultrasound, numeric pain rating scale, revised venous clinical severity score,
      the Aberdeen Varicose Vein Questionnaire, and time to return to work and normal
      activities. At the three-month visit, the need for and type of adjunctive
      procedures were recorded. Results Complete closure at three months was achieved
      in 70 (99%) of the treated veins (48 great saphenous veins, 14 accessory
      saphenous veins, eight small saphenous veins). Revised venous clinical severity
      score improved from 6.4 +/- 2.2 to 1.8 +/- 1.5 (P < .001) and Aberdeen Varicose
      Vein Questionnaire from 17.3 +/- 7.9 to 6.5 +/- 7.2 (P < .0001). Sixty-six
      percent of patients underwent tributary treatment at three months. The percentage
      of patients who required adjunctive treatments at three months was lower than had
      been predicted by the treating physicians (65% versus 96%, p=.0002). Conclusions
      Closure rates were high in the absence of the use of compression stockings or
      side branch treatment. Improvement in quality of life was significant, and the
      need for and extent of concomitant procedures was significantly less than had
      been predicted by the treating physicians.

PMID- 30227792
TI  - Cochlear implantation in children with congenital long QT syndrome: Introduction
      of an evidence-based pathway of care.
AB  - Congenital long QT syndrome (cLQTS) is an inherited cardiac ion channelopathy
      characterized by a long corrected-QT interval on the ECG, associated with a risk
      of syncope and sudden death as a result of arrhythmias. The archetypal arrhythmia
      associated with cLQTS is torsade de pointes which may degenerate into ventricular
      fibrillation. Children with Jervell and Lange-Neilsen syndrome have the
      combination of cLQTS and congenital sensorineural deafness and may present for
      cochlear implantation (CI). Sympathetic stimulation and administration of QT
      prolonging medications may trigger arrhythmias in children with cLQTS and thus
      the perioperative period is a time of increased risk of adverse events, with
      deaths reported in the CI literature. Our Paediatric Cochlear Implant Programme
      had previously elected to discontinue offering CI to children with cLQTS
      following a perioperative death. However, subsequent demand for this service by
      parents led us to develop and introduce a multidisciplinary, evidence-based
      pathway of care. This pathway modifies the perioperative management of these
      children to reduce the associated risk. We present the cases of four children
      with cLQTS who underwent CI in our specialist children's hospital.

PMID- 30227793
TI  - ?

PMID- 30227794
TI  - ?

PMID- 30227795
TI  - [Posttraumatic Osteomyelitis: Improvement in Outcome by Negative Pressure Wound
      Therapy with Instillation Technique].
AB  - Posttraumatic Osteomyelitis: Improvement in Outcome by Negative Pressure Wound
      Therapy with Instillation Technique Abstract. Surgical treatment of post
      traumatic (fistula) osteomyelitis can be difficult and is associated with an
      increased risk of later recurrence. Very often osteomyelitis is accompanied by a
      soft tissue (defective) wound. After surgical debridement, the use of the vacuum
      sealing technique can stimulate wound healing and improve local blood
      circulation. In particular, the introduction of the innovative instillation
      technique for wound sponges can increase the effectiveness of the treatment of
      the infection. By regularly rinsing the sponges with an antiseptic polyhexanide
      solution, the duration of treatment, the number of operations, the in-patient
      stay and the recurrence rate in this patient group can be statistically
      significantly reduced.

PMID- 30227796
TI  - [Technological Innovations in Diabetes Therapy].
AB  - Technological Innovations in Diabetes Therapy Abstract. In the last few years a
      whole array of technical innovations has dramatically increased treatment options
      for patients with diabetes mellitus. Capillary blood glucose measurements are
      increasingly replaced by continuous glucose monitoring. More and more insulin
      pump systems are linked up to continuous glucose monitoring, which thereby become
      ever more self-regulating. Novel ultra-long and ultra-short acting insulins have
      become available. There will soon be oral alternatives for several anti-diabetic
      treatments, which hitherto needed to be injected.

PMID- 30227797
TI  - [The Physical Examination of an 'Uncooperative' Elderly Patient].
AB  - The Physical Examination of an 'Uncooperative' Elderly Patient Abstract. The
      physical examination of uncooperative elderly patients regularly presents
      physicians in the private practice, in the hospital or nursing home with great
      challenges. The lack of cooperation itself can be an important indication of an
      underlying medical problem. Important elements to improve the patient's
      cooperation include ensuring basic needs, sufficient time and patience, adequate
      communication and good cooperation with relatives and other healthcare
      professionals. Targeted clinical observation as well as thinking in geriatric
      syndromes and unmet needs can help to raise physical findings despite limited
      cooperation. Pathological findings are indicators of impaired organ and
      functional systems and must be supplemented by a detailed examination.

PMID- 30227798
TI  - [CME Answers/"Pheochromocytoma in the General Practice", Praxis No. 17-18].

PMID- 30227800
TI  - [There Is No Such Thing as a Free Lunch].

PMID- 30227799
TI  - [CME: Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for Pyogenic
      Liver Abscesses].
AB  - CME: Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for Pyogenic
      Liver Abscesses Abstract. Pyogenic liver abscesses belong to the most common
      abdominal infections. Beside the most common pathogens, also rare forms like
      Fusobacteria, which can also be part of the natural oropharyngeal and enteral
      microbiome, may be considered to cause severe forms of abscesses of the liver.
      Since they may be more difficult to detect, they could become a challenge during
      diagnosis and therapy.

PMID- 30227801
TI  - [CME Dermatology 17/Answer: Chronic Ulcer: Infection, Skin Tumor or Travel
      Associated?]

PMID- 30227802
TI  - [CME Laboratory 57: Preanalytics].

PMID- 30227803
TI  - [Gastric Bypass: Weight Loss with Complications].
AB  - Gastric Bypass: Weight Loss with Complications Abstract. Roux-en-Y gastric bypass
      (RYGBP) is the most often performed bariatric operation worldwide with internal
      hernia as one of the main long-term complications. To our knowledge, we report
      the first case of post-ischemic small-bowel strictures observed after a
      successful operation of an internal hernia after RYGBP. During emergency surgery
      a Petersen and a Brolin hernia were diagnosed and repaired. The initially
      ischemic small intestine was recovered. However, a week later the patient
      presented herself again due to ischemia-induced small-bowel strictures. These
      were treated successfully by endoscopic balloon dilatation.

PMID- 30227805
TI  - Multiple aneurysms on the subarcuate artery arising from the anterior inferior
      cerebellar artery in a patient with a Borden type I transverse-sigmoid dural
      arteriovenous fistula manifesting as subarachnoid hemorrhage: A case report.
AB  - Background Peripheral anterior inferior cerebellar artery (AICA) aneurysms are
      rare and commonly associated with vascular malformations, such as cerebellar
      arteriovenous malformations (AVMs). We present a case wherein multiple AICA
      feeding aneurysms on the subarcuate artery as a feeding artery of a Borden type I
      transverse-sigmoid dural arteriovenous fistula (dAVF) manifested as subarachnoid
      hemorrhage. Case description A 67-year-old woman presented with acute severe
      headache. Brain computed tomography (CT) demonstrated subarachnoid hemorrhage
      mainly in the posterior fossa. A transverse-sigmoid dAVF was detected on magnetic
      resonance angiography (MRA) and three-dimensional-CT angiography (3D-CTA), with
      no cortical venous reflex. The patient underwent conventional angiography, which
      showed multiple aneurysms on a small branch of the AICA, feeding a transverse
      sigmoid dAVF (Borden type I). The AICA aneurysms seemed flow dependent and
      ruptured owing to high-flow arteriovenous shunts through the dAVF. Based on the
      source images of the MRA, the small artery arising from the AICA was considered
      the subarcuate artery, and it was confirmed on 3D-CTA after the artery was
      successfully embolized with Onyx without any complications. Multiple aneurysms on
      the subarcuate artery are extremely rare, and the artery has not been identified
      as a feeding artery of the transverse-sigmoid dAVF. Conclusion A rare case of
      multiple ruptured aneurysms on the subarcuate artery was reported in a patient
      with a Borden type I dAVF at the transverse-sigmoid sinuses manifesting as
      subarachnoid hemorrhage. Onyx embolization of the parent artery occlusion was
      feasible and useful in treating this type of feeding artery aneurysm of the AICA
      with a dAVF.

PMID- 30227804
TI  - [Treatment of Advanced Prostate Carcinoma - an Interdisciplinary Recommendation].

PMID- 30227806
TI  - A retained guidewire fractured with subsequent pericardial tamponade two years
      after endovascular neurointervention.
AB  - Entrapment of aneurysm embolization hardware is an extremely rare complication of
      endovascular neurointerventional procedures. We describe a case of a retained
      guidewire in a 42-year-old male during an aneurysm embolization. After
      unsuccessful attempts at removal via interventional methods, we decided to leave
      the guidewire within the vessel. A guidewire fracture resulted in several
      fragments in the carotid artery and aorta with subsequent cardiac tamponade,
      pseudoaneurysm and aortojejunal fistula two years later. The fragments in the
      aorta were removed via interventional and surgical methods. We advocate early
      surgical management of the retained guidewires after unsuccessful retractions via
      interventional methods. Meticulous and gentle maneuvering is necessary to prevent
      such serious complications.

PMID- 30227807
TI  - Asystole during onyx embolisation of a dural AV fistula: The trigeminocardiac
      reflex.
AB  - There are fewer than 20 published case reports of bradycardia or asystole during
      intracranial embolisation procedures. These are well described in open
      neurosurgical procedures, particularly involving the skull base. We present a
      case of a 59-year-old male patient who presented for elective embolisation of a
      dural arteriovenous fistula. During the injection of Onyx, the patient experience
      sudden asystole, which recurred after a second Onyx injection. Following
      successful treatment, a third injection proceeded without incident.

PMID- 30227808
TI  - Comparing the results of intradiscal ozone injection to treat different types of
      intervertebral disc herniation based on MSU classification.
AB  - Purpose To evaluate the therapeutic efficacy of intradiscal ozone injection in
      reducing pain and improving patients' performance in different types of
      intervertebral disc herniation based on Michigan State University (MSU)
      classification. Patients and methods Consecutive patients with low back pain and
      radiculopathy treated in our center with ozone chemonucleolysis from May 2017
      through to January 2018 entered the study. Patients had a disc herniation
      classified as group 1-A, 2-A, 1-B, 2-B, 1-C, 2-C, 1-AB or 2-AB based on MSU
      classification in magnetic resonance imaging. In all patients entering the study
      the severity of pain was recorded according to the visual analog scale criteria
      before and one and three months after the end of treatment. Oswestry Low Back
      Pain Disability Index (ODI) was used to compare patients' performance before and
      after the treatment. Results In total 128 patients (60 females and 68 males) with
      mean age of 40.1 +/- 10.7 entered the study. The patients were divided into eight
      groups based on MSU classification each including 16 patients. The reduction of
      pain severity and ODI score compared to baseline was statistically significant in
      all groups both in the first month and the third month after treatment. There was
      also a statistically significant difference between groups regarding the
      reduction of pain and ODI score indicating significantly worse treatment outcomes
      in groups 1-C, 2-C and 2-AB. Conclusion Based on our findings it seems that MSU
      classification can be used in patients' selection to achieve the best treatment
      outcome after intradiscal ozone injection among patients with lumbar disc
      herniation.

PMID- 30227809
TI  - Endovascular management of penetrating and non-penetrating aortic injury.
AB  - Aortic trauma is a devastating injury often associated with significant
      polytrauma. Penetrating injury of the aorta is highly lethal and therefore rarely
      encountered in the hospital setting. The management of blunt trauma of the aorta
      has changed significantly over the past decade, principally due to improved
      imaging technology and the development of endovascular therapy. The most common
      site of injury is the proximal descending thoracic aorta. The degree of aortic
      wall injury guides the indication for therapy, while a combination of the degree
      of injury and the extent of co-morbid injuries drives the timing of repair. Lower
      grade injuries frequently do not require any surgical intervention. Thoracic
      aortic endograft repair can be performed in a safe, expeditious fashion. Short
      term and mid-term outcomes appear excellent, with patient survival based mainly
      on concomitant traumatic injuries. Long-term outcomes are less well known. Future
      endeavors will be guided toward gaining a better understanding of the indications
      for repair and the long-term outcomes for endograft devices designed for this
      purpose.

PMID- 30227810
TI  - Self-assembly of functional nanostructures by short helical peptide building
      blocks.
AB  - The self-assembly of short peptide building blocks into well-ordered
      nanostructures is a key direction in bionanotechnology. The formation of beta
      sheet organizations by short peptides is well explored, leading to the
      development of a wide range of functional assemblies. Likewise, many natural
      proteinaceous materials, such as silk and amyloid fibrils, are based on beta
      sheet structures. In contrast, collagen, the most abundant protein in mammals, is
      based on helical arrangement. Similar to beta-sheet structures, short helical
      peptides have been recently discovered to possess a diverse set of
      functionalities with the potential to fabricate artificial self-assembling
      materials. Here, we outline the functional roles of self-assembled nanostructures
      formed by short helical peptides and their potential as artificial materials. We
      focus on the association between self-assembled mesoscale structures and their
      material function and demonstrate the way by which this class of building blocks
      bears the potential for diverse applications, such as the future fabrication of
      smart devices.

PMID- 30227811
TI  - Serological Electrodetection of Rheumatoid Arthritis Using Mimetic Peptide.
AB  - BACKGROUND: Rheumatoid arthritis is the most common inflammatory autoimmune
      disease in the world. Recently new targets for its detection were developed as
      alternatives to classic biomarkers, including the M-12 peptide, that mimics
      carbonic anhydrase III. Thus, the application of this peptide for the development
      of new detection devices is attractive. OBJECTIVE: Our goal was to construct a
      modified electrode for immobilization of M-12 peptide and detection of a
      rheumatoid arthritis biomarker in serum of patients. METHODS: 3-Hydroxybenzoic
      acid was electropolymerized onto graphite electrodes, and M-12 peptide was
      immobilized by adsorption. Negative and positive serum samples for rheumatoid
      arthritis were diluted and applied onto the electrode. Detection was carried in
      potassium ferrocyanide/ ferricyanide solution by differential pulse voltammetry.
      Atomic force microscopy and scanning electron microscopy were used to evaluate
      electrode surfaces. RESULTS: Cyclic voltammograms indicated the poly(3
      hydroxybenzoic acid) formation and increase of electroactive area. Immobilization
      of M-12 probe increased current by 1.2 times, and negative serum addition caused
      no suitable difference. However, positive serum showed expressive decrease in the
      current signal of about 2.2 times, possibly due to steric hindrance when the anti
      CA3 antibody interacts with the M-12 peptide, decreasing the electron transfer.
      Microscopies images corroborated with the electrochemical detection, showing
      evident changes in the morphology of the electrode surfaces. CONCLUSION: The
      bioelectrode was able to discriminate positive and negative serum samples of
      rheumatoid arthritis by a considerable decrease in the current signal value.
      Morphological analyses supported the electrochemical results. Thus, the
      constructed bioelectrode offers a new platform for detection of rheumatoid
      arthritis.

PMID- 30227812
TI  - The immunological functions of muramyl dipeptide compound adjuvant on humoral,
      cellular-mediated and mucosal immune responses to PEDV inactivated vaccine in
      mice.
AB  - BACKGROUND: The muramyl dipeptide compound adjuvant, CVC1303, was one new
      resigned adjuvant to PEDV inactivated vaccine. Exploring the effects of CVC1303
      on the immune induction to PEDV vaccine was of vital importance to the clinical
      application. OBJECTIVES: Here we explored the functions of CVC1303 on the
      humoral, cellular and mucosal immune response to PEDV vaccine in mice
      immunization. METHOD: Mice were twice subcutaneously injected with PEDV vaccine
      including high, medium and low dosages CVC1303, respectively. On 30th day after
      the second immunization, sera samples were collected from the immunized mice to
      measure PEDV-specific IgG and IgG subclasses levels, and lymphocytes were
      isolated to detect T cell subtype and intracellular IL-4 and IL-6 cytokine
      productions, and the expressions of co-stimulatory molecule on dendritic cells in
      the immunized mice. Small intestinal and lung washings were collected on 30th and
      47th day after the second immunization to measure PEDV-specific IgA levels, and
      SP immunohistochemical method staining was employed to analyze the deviations of
      IgA+ positive cells in the small intestinal of the immunized mice. RESULTS: Our
      investigation proved the strong regulatory roles of CVC1303 on PEDV-specific IgG
      and IgG1 antibody and cytokines productions, and the significant increased
      CD3+CD4+T cells subpopulation and expressions of co-stimulatory molecules on
      dendritic cells in the immunized mice. Moreover, our findings verified the
      significantly enhanced PEDV-specific IgA antibody titers in small intestinal and
      lung in the mice immunized with PEDV vaccine and CVC1303. CONCLUSION: compound
      adjuvant CVC1303 could effectively improve the PEDV-specific immune responses and
      mucosal immune, which provided an experimental basis for the further clinical
      application of new adjuvant CVC1303 and the development of improvement on the
      mucosal immune response.

PMID- 30227813
TI  - The Value of Urinary Cystatin C Level to Predict Neonatal Kidney Injury.
AB  - BACKGROUND: The role of urinary cystatin C to early predict acute kidney injury
      (AKI) in children and neonates remains uncertain. The present study aimed to
      assess and compare the level of urinary cystatin C in neonates with and those
      without AKI. METHODS: This cross-sectional study was performed on 55 available
      neonates who were involved by AKI and admitted to the neonatal department at Ali
      Asghar hospital in Tehran in 2016. 97 neonates with jaundice and normal serum
      creatinine level were randomly selected as the control group. In both groups and
      on admission, the urine levels of cystatin C and creatinine were measured.
      RESULTS: The average urinary level of cystatin C was 162.87 +/- 56.50 mmol/mole
      creatinine in the group with AKI and 68.06 +/- 57.16 mmol/mole creatinine in the
      control group that was significantly higher in former group (p < 0.001). The
      measurement of cystatin C level in urine could predict kidney injury with a
      sensitivity of 98.2%, a specificity of 39.2%, a positive predictive value of
      47.8%, a negative predictive value of 97.4%, and an accuracy of 60.5%. Assessment
      of the area under the receiver operating characteristic (ROC) analysis showed
      that measuring urinary cystatin C level could effectively discriminate kidney
      injury from normal kidney condition in neonates (AUC = 0.868, 95CI: 0.811 -
      0.925, P < 0.001). The best cutoff value of urinary cystatin C level to predict
      kidney injury was shown to be 41.5 mmol/mole creatinine yielding a sensitivity of
      98.2% and a specificity of 46.4%. CONCLUSION: Measurement of cystatin C in urine
      is an early sensitive method to diagnose neonatal kidney injury.

PMID- 30227814
TI  - Cancer Nanotechnology: A New Revolution for Cancer Diagnosis and Therapy.
AB  - Background- Nanotechnology is gaining significant attention worldwide for cancer
      treatment. Nano-biotechnology encourages the combination of diagnostics with
      therapeutics, which is a vital component of a customized way to deal with the
      malignancy. Nanoparticles are being used as Nanomedicine which participates in
      diagnosis and treatment of various diseases including cancer. The unique
      characteristic of Nanomedicine i.e. their high surface to volume ratio enables
      them to tie, absorb, and convey small biomolecule like DNA, RNA, drugs, proteins,
      and other molecules to the targeted site and thus enhances the efficacy of
      therapeutic agents. Objective- The objective of the present article is to provide
      an insight of several aspects of nanotechnology in cancer therapeutics such as
      various nanomaterials as drug vehicle, drug release strategies and role of
      nanotechnology in cancer therapy. Methods- We performed an extensive search on
      bibliographic database for research article on nanotechnology and cancer
      therapeutics and further compiled the necessary information from various articles
      into the present article. Result- Cancer nanotechnology confers a unique
      technology against cancer through early diagnosis, prevention, personalized
      therapy by utilizing nanoparticles and quantum dots. Nano-biotechnology plays an
      important role in the discovery of cancer biomarkers. Quantum dots, gold
      nanoparticles, magnetic nanoparticles, carbon nanotubes, gold nanowires etc. have
      been developed as a carrier of biomolecules that can detect cancer biomarkers.
      Nanoparticle assisted cancer detection and monitoring involves biomolecules like
      proteins, antibody fragments, DNA fragments, and RNA fragments as the base of
      cancer biomarkers. Conclusion- This review highlights various approaches of
      cancer nanotechnology in the advancement of cancer therapy.

PMID- 30227815
TI  - The role of xenobiotic receptors on hepatic glycolipid metabolism.
AB  - PXR (pregnane X receptor) and CAR (constitutive androstane receptor) are termed
      as xenobiotic receptors, which are known as core factors in the regulation of the
      transcription of metabolic enzymes and drug transporters. However, accumulating
      evidence has shown that PXR and CAR exert their effects on energy metabolism
      through the regulation of gluconeogenesis, lipogenesis, and beta-oxidation.
      Therefore, PXR and CAR may become new therapeutic targets for metabolic syndrome,
      including obesity and diabetes. In this review, we will summarize recent advances
      to show how xenobiotic receptors regulate energy metabolism.

PMID- 30227816
TI  - Endless pursuit:evolution of insulin administration.
AB  - Diabetes mellitus is a chronic metabolic health condition affecting the steady
      state of blood sugar level. The usual method of administration is subcutaneous
      injection of insulin. There are several ways to subcutaneously inject insulin,
      such as syringes, insulin pens, and insulin pumps. However, subcutaneous
      injections of insulin can lead to discomfort, pain and local infection. This
      review focuses on traditional methods of insulin administration, non-invasive
      approaches, and new insulin therapy technologies, and the advantages and
      disadvantages of these approaches, as well as future development prospects are
      also discussed.

PMID- 30227817
TI  - Aspects of Nanomaterials in Wound Healing.
AB  - Wound infections impose a remarkable clinical challenge that has a considerable
      influence on morbidity and mortality of patients, influencing the cost of
      treatment. The unprecedented advancements in molecular biology have come up with
      new molecular and cellular targets that can be successfully applied to develop
      smarter therapeutics against diversified categories of wounds such as acute and
      chronic wounds. However, nanotechnology-based diagnostics and treatments have
      achieved a new horizon in the arena of wound care due to its ability to deliver a
      plethora of therapeutics into the target site, and to target the complexity of
      the normal wound-healing process, cell type specificity, and plethora of
      regulating molecules as well as pathophysiology of chronic wounds. The emerging
      concepts of nanobiomaterials such as nanoparticles, nanoemulsion, nanofibrous
      scaffolds, graphene-based nanocomposites, etc., and nano-sized biomaterials like
      peptides/proteins, DNA/RNA, oligosaccharides have a vast application in the arena
      of wound care. Multi-functional, unique nano-wound care formulations have
      acquired major attention by facilitating the wound healing process. In this
      review, emphasis has been given to different types of nanomaterials used in
      external wound healing (chronic cutaneous wound healing); the concepts of basic
      mechanisms of wound healing process and the promising strategies that can help in
      the field of wound management.

PMID- 30227818
TI  - Breaking the Barrier of Cancer Through Liposome Loaded with Phytochemicals.
AB  - Currently, the most important cause of death is cancer. To treat the cancer there
      are a number of drugs existing in the market but no drug is found to be
      completely safe and effective. The toxicity of the drugs is the key problem in
      the cancer chemotherapy. However, plants and plant derived bioactive molecule
      have proved safe and effective in the treatment of cancers. Phytochemicals that
      are found in fruits, vegetables, herbs, and plant extract have been usually used
      for treating cancer. It has been established that several herbal drug have a
      strong anticancer activity. However, their poor bioavailability, solubility, and
      stability have severely restricted their use. These problems can be overcome by
      incorporating the herbal drug in nanolipolomal vesicles. In last few decades,
      researcher have used herbal drug loaded nanoliposome for the treatment and
      management of a variety of cancers. Presently, a number of liposomal formulations
      are on the market for the treatment of cancer and many more are in pipe line.
      This review discusses about the tumor microenvironment, targeting mechanism of
      bioactive phytochemicals to the tumor tissue, background of nanoliposome, and the
      potential therapeutic applications of different bioactive phytochemicals loaded
      nanoliposome in cancer therapy.

PMID- 30227819
TI  - Alzheimer Disease - Future Therapy Based on Dendrimers.
AB  - Alzheimer disease (AD) is characterized by the loss of neurons. It is the most
      common cause of dementia in the elderly population accompanied by pathological
      degeneration of neurofibrillary tangles. Senile plaques are formed with beta
      amyloid, hyperphosphoryled tau protein, apolipoprotein E and presenilin
      associated with protease activity [amyloid beta (Abeta), gamma-secretase
      (gammaS)]. The molecular mechanisms of neurodegeneration include apoptosis,
      oxidative shock (free radical generation), inflammation, immune activation, and
      others. The lack of effective treatments for AD stems mainly from the incomplete
      understanding of causes of AD. Currently, there are several hypotheses explaining
      the early mechanisms of AD pathogenesis. Recent years witnessed an unprecedented
      research growth in the area of nanotechnology, which uses atomic, molecular and
      macromolecular methods to create products in microscale (nanoscale) dimensions.
      In this article, we have discussed the role of nanotechnology in the development
      and improvement of techniques for early diagnosis and effective treatment of AD.
      Since AD pathology is practically irreversible, applications of disease-modifying
      treatments could be successful only if early diagnosis of AD is available. The
      current review article highlights various possibilities for the diagnosis and
      therapy of AD, and investigates potential adaptation of nanoparticles-dendrimers,
      a class of well-defined branched polymers, chemically synthesized with a well
      defined shape, size and nanoscopic physicochemical properties reminiscent of the
      proteins for the treatment of neurodegenerative diseases.

PMID- 30227820
TI  - Three generations of beta-blockers: history, class differences and clinical
      applicability.
AB  - BACKGROUND: Beta-adrenergic receptors are expressed in cardiomyocytes and
      activated by either noradrenaline released from sympathetic synapses or
      circulating catecholamines. Their corresponding receptors have three subtypes,
      namely, beta1, beta2 and beta3, which are members of the G protein-coupled
      receptors (GPCRs) family. Activation of beta1-adrenergic receptors causes various
      physiological reactions including cardiac contraction and renin secretion from
      juxtaglomerular cells of the kidney. Antagonists of beta-adrenergic receptors,
      known as beta-blockers, have been used effectively for over four decades and have
      beneficial effects in the treatment of cardiovascular diseases. There are three
      generations of beta-blockers according to their pharmacological properties. First
      generation beta-blockers are non-selective, blocking both beta1- and beta2
      receptors; second-generation beta-blockers are more cardioselective in that they
      are more selective for beta1-receptors; and third-generation beta-blockers are
      highly selective drugs for beta1-receptors. The latter also display vasodilator
      actions by blocking alpha1-adrenoreceptors and activating beta3-adrenergic
      receptors. In addition, third-generation beta-blockers exhibit angiogenic,
      antioxidant, anti-proliferative, anti-hypertrophic and anti-apoptotic activities
      among other effects that are still under investigation. CONCLUSION: The objective
      of this review is to describe the evolution observed during the development of
      the three distinctive generations, thereby highlighting the advantages of third
      generation beta-blockers over the other two drug classes.

PMID- 30227821
TI  - Basic concepts of a contrast injection protocols for coronary computed tomography
      angiography.
AB  - Coronary computed tomography angiography (CTA) is a rapidly growing, robust and
      established noninvasive imaging modality for the evaluation of coronary artery
      diseases. During coronary CTA, sufficient arterial enhancement is essential for
      the accurate assessment of coronary artery diseases. To obtain optimal contrast
      enhancement and perform appropriate clinical coronary CTA, physicians,
      radiologists, and radiology technologists should acquire a basic knowledge of
      contrast injection protocols. This review article summarizes the basic concepts
      of contrast injection protocols for coronary CTA.

PMID- 30227822
TI  - Differentiation of pluripotent stem cells into nucleus pulposus progenitor cells
      for intervertebral disc regeneration.
AB  - Low back pain (LBP) is one of the world's most common musculoskeletal diseases,
      and is frequently associated with intervertebral disc degeneration (IDD). While
      the main cause of IDD is commonly attributed to a reduced number of nucleus
      pulposus (NP) cells, current treatment strategies (both surgical and more
      conservative) fail to replenish NP cells or reverse the pathology. Cell
      replacement therapies are an attractive alternative for treating IDD. However,
      injecting intervertebral disc (IVD) cells, chondrocytes, or mesenchymal stem
      cells into various animal models of IDD indicate that transplanted cells
      generally fail to survive and engraft into the avascular IVD niche. Whereas
      pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs)
      and embryonic stem cells (ESCs), hold great potential for revolutionizing
      regenerative medicine, current protocols for differentiating these cells into NP
      like cells are inadequate. Nucleus pulposus progenitor cells (NPPCs), which are
      derived from the embryonic notochord, can not only survive within the harsh
      hypoxic environment of the IVD, but they also efficiently differentiate into NP
      like cells. Here we provide an overview of the latest progresses in repairing
      degenerated IVDs using PSCs and NPPCs. We also discuss the molecular pathways by
      which PSCs differentiate into NPPCs in vitro and in vivo and propose a new, in
      vivo IDD therapy.

PMID- 30227823
TI  - Ductal cell reprogramming to insulin-producing beta-like cells as a potential
      beta cell replacement source for chronic pancreatitis.
AB  - Islet cell auto-transplantation is a novel strategy for maintaining blood glucose
      levels and improving the quality of life in patients with chronic pancreatitis
      (CP). Despite the many recent advances associated with this therapy, obtaining a
      good yield of islet infusate still remains a pressing challenge. Reprogramming
      technology, by making use of the pancreatic exocrine compartment, can open the
      possibility of generating novel insulin-producing cells. Several lineage-tracing
      studies present evidence that exocrine cells undergo dedifferentiation into a
      progenitor-like state from which they can be manipulated to form insulin
      producing cells. This review will present an overview of recent reports that
      demonstrate the potential of utilizing pancreatic ductal cells (PDCs) for
      reprogramming into insulin-producing cells, focusing on the recent advances and
      the conflicting views. A large pool of ductal cells is released along with islets
      during the human islet isolation process, but these cells are separated from the
      pure islets during the purification process. By identifying and improving
      existing ductal cell culture methods and developing a better understanding of
      mechanisms by which these cells can be manipulated to form hormone-producing
      islet-like cells, PDCs could prove to be a strong clinical tool in providing an
      alternative beta cell source, thus helping CP patients maintain their long-term
      glucose levels.

PMID- 30227824
TI  - Neuroprotective Effects of Trolox, Human Chorionic Gonadotropin, and Carnosic
      Acid on Hippocampal Neurodegeneration After Ischemia-reperfusion Injury.
AB  - INTRODUCTION: One of the serious complications of stroke is memory impairment,
      which is considered as one of the complications of reperfusion of tissue. The
      present study was designed to compare the effect of administration of Trolox,
      carnosic acid and Human Chorionic Gonadotropin (HCG) immediately after
      reperfusion of the stroke tissue on the memory and hippocampal histology. METHOD:
      Ischemia reperfusion model (IRI) was created by bilateral occlusion of the common
      carotid artery for 15 minutes and the first dose was administered immediately
      after reperfusion. 10 days after ischemia, passive avoidance memory test and
      apoptotic protein levels were evaluated. RESULTS: Cerebral Ischemia perfusion
      reduced the time of latency in entering the dark box in the ischemic group.
      Administration of Trolox and HCG increased this latency time, while treatment
      with carnosic acid had no effect. Also, IRI significantly reduced the number of
      healthy cells in the hippocampus. Administration of Trolox, carnosic acid and HCG
      increased the number of healthy cells and decreased the expression of Caspase-3
      and Bax, but significantly increased expression of Bcl-2 compared to the ischemic
      group. CONCLUSION: Findings indicate the beneficial effects of HCG and Trolox on
      the improvement of memory and the number of healthy cells in the hippocampal
      region. It is worth noting that the amount of apoptosis in the hippocampus was
      significantly reduced by Trolox, HCG and Carnosic acid.

PMID- 30227825
TI  - Nanotechnological Carriers For Treatment Of Acne.
AB  - BACKGROUND: Acne is a multifactorial skin disease associated with pilosebaceous
      unit and caused by bacteria Propionibacterium acnes and Acne vulgaris. Near about
      95% people throughout the world suffer from acne at some point in their life
      span. This disease is more prominent in adults compared to neonates and
      prepubescent children. Conventionally it is treated with either creams or gels
      having large number of side effects on patients. METHODS: We searched about
      recent advancements in the use of nanotechnological carriers for effective
      treatment of acne. We focused on the use of liposomes, niosomes, microemulsions,
      microsponge, microspheres, and nanoparticles to improve anti-acne therapy.
      RESULTS: The encapsulation of anti-acne drugs in various nanotechnological
      carriers improve their efficacy and reduce side effects. These carriers show
      controlled drug release and improved drug penetration even upto pilosebaceous
      unit of skin. Local tolerability of anti-acne molecules can be improved by
      adjusting the concentration in nanotechnological carriers. CONCLUSIONS:
      Nanotechnological carriers have opened a new window to design novel, effective
      and low dose systems for effective eradication acne disease. However, very few
      nanocarrier based formulations are available in market for topical use and much
      progress is required in this field to improve anti-acne therapy.

PMID- 30227826
TI  - Ultra structural observations of anti-leishmanial effects of new synthetic 3
      imidazolylflavanoneson Leishmania majorusing scanning electron and atomic force
      microscopes.
AB  - AIM AND BACKGROUND: Azoles as antifungal drugs, has been used to treat
      leishmaniasis for many years. Several evidences suggesting that the primary
      target of azoles is the heme protein, which cocatalyzes cytochrome P-450
      dependent 14alpha-demethylation of lanosterol. Little is known about the
      structural changes caused by azoles with atomic force microscopy (AFM) or
      scanning electron microscopy (SEM). In the current work several patented
      antileishmanial agents reviewed (US8809555) (US 0269803 A1) (TW201802093 A).
      Present study aimed to determine ultrastructural damage in Leishmania major
      (L.major) induced by newly synthesized azole. METHODS: In this study we
      investigated the morphological alterations of the parasite treated with our new
      synthesized azole namely trans-2-(4-chlorophenyl)-2,3-dihydro-3-(1H-imidazol-1
      yl)-4H-1-benzopyran-4-one (IF-2) against L.major promastigotes stage using two
      high resolution microscopic techniques: atomic force microscopy and scanning
      electron microscopy. RESULTS: The results showed remarkable topographical and
      morphological alterations on cell membrane of promastigote stage of L. major
      treated with the potent investigated azole (IF-2) ( IC50 values <=8.9 ug/mL).
      Both techniques revealed membrane damage and also losing the flagellum in
      observed cells. CONCLUSION: Our results strongly confirm the Leishmania cell wall
      as a potent target for the new synthesized azole (IF-2). Accordingly, focus on
      membrane integrity and glycoconjugates of Leishmania parasite to design new
      therapeutic agents is recommended.

PMID- 30227827
TI  - Drug Delivery for Cancer Immunotherapy and Vaccines.
AB  - Cancer cells are able to avoid immune surveillance and exploit the immune system
      to grow and metastasize. With the development of nano- and micro-particles, there
      has been a growing number of immunotherapy delivery systems developed to elicit
      innate and adaptive immune responses to eradicate cancer cells. This can be
      accomplished by training resident immune cells to recognize and eliminate cells
      with tumor-associated antigens or by providing external stimuli to enhance tumor
      cell apoptosis in the immunosuppressive tumor microenvironment (TME). In this
      review we will focus on nano- and micro-particle (NP and MP) based
      immunotherapies and vaccines used to elicit a potent and sustained antitumor
      immune response.

PMID- 30227828
TI  - Genetic selection against intrauterine growth retardation in piglets: a problem
      at the piglet level with a solution at the sow level.
AB  - BACKGROUND: In polytocous livestock species, litter size and offspring weight act
      antagonistically; in modern pig breeds, selection for increased litter size has
      resulted in lower mean birth weights, an increased number of small piglets and an
      increased number of those affected by varying degrees of intrauterine growth
      retardation (IUGR). IUGR poses life-long challenges, both mental, with
      morphological brain changes and altered cognition, and physical, such as
      immaturity of organs, reduced colostrum intake and weight gain. In pigs, head
      morphology of newborn piglets is a good phenotypic marker for identifying such
      compromised piglets. Growth retardation could be considered as a property of the
      dam, in part due to either uterine capacity or insufficiency. A novel approach to
      this issue is to consider the proportion of IUGR-affected piglets in a litter as
      an indirect measure of uterine capacity. However, uterine capacity or sufficiency
      cannot be equated solely to litter size and thus is a trait difficult to measure
      on farm. RESULTS: A total of 21,159 Landrace * Large White or Landrace * White
      Duroc piglets (born over 52 weeks) with recorded head morphology and birth
      weights were followed from birth until death or weaning. At the piglet level, the
      estimated heritability for IUGR (as defined by head morphology) was low at 0.01
      +/- 0.01. Piglet direct genetic effects of birth weight (h2 = 0.07 +/- 0.02) were
      strongly negatively correlated with head morphology (- 0.93), in that IUGR
      affected piglets tended to have lower birth weights. At the sow level, analysis
      of the proportion of IUGR-affected piglets in a litter gave a heritability of
      0.20 +/- 0.06, with high and negative genetic correlations of the proportion of
      IUGR-affected piglets with average offspring birth weight (- 0.90) and with the
      proportion of piglets surviving until 24 h (- 0.80). CONCLUSIONS: This suggests
      that the proportion of IUGR-affected piglets in a litter is a suitable indirect
      measure of uterine capacity for inclusion in breeding programmes that aim at
      reducing IUGR in piglets and improving piglet survival.

PMID- 30227829
TI  - Detecting gene-gene interactions for complex quantitative traits using
      generalized fuzzy classification.
AB  - BACKGROUND: Quantitative traits or continuous outcomes related to complex
      diseases can provide more information and therefore more accurate analysis for
      identifying gene-gene and gene- environment interactions associated with complex
      diseases. Multifactor Dimensionality Reduction (MDR) is originally proposed to
      identify gene-gene and gene- environment interactions associated with binary
      status of complex diseases. Some efforts have been made to extend it to
      quantitative traits (QTs) and ordinal traits. However these and other methods are
      still not computationally efficient or effective. RESULTS: Generalized Fuzzy
      Quantitative trait MDR (GFQMDR) is proposed in this paper to strengthen
      identification of gene-gene interactions associated with a quantitative trait by
      first transforming it to an ordinal trait and then selecting best sets of genetic
      markers, mainly single nucleotide polymorphisms (SNPs) or simple sequence length
      polymorphic markers (SSLPs), as having strong association with the trait through
      generalized fuzzy classification using extended member functions. Experimental
      results on simulated datasets and real datasets show that our algorithm has
      better success rate, classification accuracy and consistency in identifying gene
      gene interactions associated with QTs. CONCLUSION: The proposed algorithm
      provides a more effective way to identify gene-gene interactions associated with
      quantitative traits.

PMID- 30227830
TI  - Brittle cornea syndrome: a case report and review of the literature.
AB  - BACKGROUND: To report a patient who presented with bluish scleral discoloration,
      keratoconus, and progressive high myopia. CASE PRESENTATION: A 6-year-old Chinese
      female patient presented with a significant bluish discoloration of the sclera in
      both eyes and extreme corneal thinning with anterior corneal protrusion. General
      pediatric physical examination was normal for all systems and no genetic
      disorders known were observed. CONCLUSIONS: We aim to highlight the importance of
      diagnosis and treatment of patients suffering from Brittle cornea syndrome.
      Timely diagnosis and early provision of protective glasses seem to be the most
      important step in treating BCS. To our knowledge, this is the first case of BCS
      being reported in the Asia area.

PMID- 30227831
TI  - Virological failure among adolescents on ART, Harare City, 2017- a case-control
      study.
AB  - BACKGROUND: Zimbabwe is on track towards achieving viral suppression among adults
      (87%). However, adolescents have only achieved 44% by 2016. In Harare city, 57%
      of adolescents had attained viral suppression after 12 months on ART compared to
      88% among adults. We determined factors associated with virological failure among
      adolescents (age 10-19 years) on antiretroviral therapy (ART) in Harare city.
      METHODS: We conducted a one to one unmatched case control study among 102
      randomly recruited case: control pairs at the two main infectious disease
      hospitals in Harare. A case was any adolescent who presented with VL > 1000c/ml
      after at least 12 months on ART. A control was any adolescent who presented with
      VL < 1000c/ml after at least 12 months on ART. Interviewer administered
      questionnaires were used to collect data. Epi Info 7 was used to generate
      frequencies, means, proportions, ORs and p-values at 95% CI. RESULTS: We
      interviewed 102 case-control pairs. Poor adherence to ART [aOR = 8.15, 95% CI
      (2.80-11.70)], taking alcohol [aOR = 8.46, 95% CI (3.22-22.22)] and non-
      disclosure of HIV status [aOR = 4.56, 95% CI (2.20-9.46)] were independent risk
      factors for virological failure. Always using a condom [aOR = 0.04, 95% CI (0.01
      0.35)], being on second line treatment [aOR = 0.04, 95% CI (0.23-0.81)] and
      belonging to a support group [aOR = 0.41, 95% CI (0.21-0.80)] were protective.
      CONCLUSION: Poor adherence, alcohol consumption and non-disclosure increased the
      odds of virological failure. Based on these findings support should focus on
      behavior change and strengthening of peer to peer projects to help address issues
      related to disclosure and adherence. Further operational research should aim to
      define other components of effective adherence support for adolescents with
      virological failure.

PMID- 30227832
TI  - Emotional prosodic change detection in autism Spectrum disorder: an
      electrophysiological investigation in children and adults.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is characterized by atypical behaviors
      in social environments and in reaction to changing events. While this dyad of
      symptoms is at the core of the pathology along with atypical sensory behaviors,
      most studies have investigated only one dimension. A focus on the sameness
      dimension has shown that intolerance to change is related to an atypical pre
      attentional detection of irregularity. In the present study, we addressed the
      same process in response to emotional change in order to evaluate the interplay
      between alterations of change detection and socio-emotional processing in
      children and adults with autism. METHODS: Brain responses to neutral and
      emotional prosodic deviancies (mismatch negativity (MMN) and P3a, reflecting
      change detection and orientation of attention toward change, respectively) were
      recorded in children and adults with autism and in controls. Comparison of
      neutral and emotional conditions allowed distinguishing between general deviancy
      and emotional deviancy effects. Moreover, brain responses to the same neutral and
      emotional stimuli were recorded when they were not deviants to evaluate the
      sensory processing of these vocal stimuli. RESULTS: In controls, change detection
      was modulated by prosody: in children, this was characterized by a lateralization
      of emotional MMN to the right hemisphere, and in adults, by an earlier MMN for
      emotional deviancy than for neutral deviancy. In ASD, an overall atypical change
      detection was observed with an earlier MMN and a larger P3a compared to controls
      suggesting an unusual pre-attentional orientation toward any changes in the
      auditory environment. Moreover, in children with autism, deviancy detection
      depicted reduced MMN amplitude. In addition in children with autism, contrary to
      adults with autism, no modulation of the MMN by prosody was present and sensory
      processing of both neutral and emotional vocal stimuli appeared atypical.
      CONCLUSIONS: Overall, change detection remains altered in people with autism.
      However, differences between children and adults with ASD evidence a trend toward
      normalization of vocal processing and of the automatic detection of emotion
      deviancy with age.

PMID- 30227833
TI  - Do elevated symptoms of depression predict adherence and outcomes in the UPBEAT
      randomised controlled trial of a lifestyle intervention for obese pregnant women?
AB  - BACKGROUND: Lifestyle interventions for obese pregnant women have been widely
      researched but little is known about predictors of low adherence or poor
      outcomes. This study evaluated the prospective associations between elevated
      symptoms of antenatal depression and gestational diabetes, adherence and
      gestational weight gain in a large RCT of a behavioural intervention for obese
      pregnant women. The effect of the intervention on symptoms of depression at
      follow-up was also examined. METHODS: The UPBEAT RCT randomised 1555 obese
      pregnant women to receive a dietary and physical activity lifestyle intervention
      or standard care. Symptoms of antenatal depression were assessed with the
      Edinburgh Postnatal Depression Scale at baseline (15+ 0-18+ 6 weeks' gestation)
      and follow-up (27+ 0-28+ 6 weeks' gestation). Gestational diabetes was assessed
      with an oral glucose tolerance test at 27+ 0-28+ 6 weeks' gestation. Adherence
      was pre-defined as receiving at least 5 of 8 intervention sessions. Gestational
      weight gain was calculated as the difference between pre-pregnancy weight
      (estimated as measured baseline weight minus 1.25 kg) and last measured weight at
      34+ 0-36+ 0 weeks' gestation. Due to substantial missing data in certain
      variables, multiple imputation was used to impute missing data. Women who were no
      longer pregnant at 27+ 0-28+ 6 weeks' gestation were excluded from the sample for
      these analyses. RESULTS: One thousand five-hundered twenty-six women were
      included in these analyses following multiple imputation; 797 (52.2%) had
      complete data. 13.4% had elevated symptoms of antenatal depression at baseline.
      There was no evidence for associations between antenatal depression status and
      gestational diabetes (adjusted OR 0.80, 95%CI 0.52 to 1.22, p = 0.30), adherence
      (adjusted OR 1.16, 95%CI 0.63 to 2.15, p = 0.63) or gestational weight gain
      (adjusted regression coefficient 0.52, 95%CI -0.26 to 1.29, p = 0.19). The
      intervention was not associated with change in depressive symptoms at follow-up
      (regression coefficient 0.003, 95%CI -0.49 to 0.49, p = 0.99). Similar results
      were obtained in complete case analyses. CONCLUSIONS: Elevated symptoms of
      antenatal depression did not predict gestational diabetes, adherence or
      gestational weight gain in this large RCT of a lifestyle intervention for obese
      pregnant women. The intervention also did not influence symptoms of depression at
      follow-up. Obese pregnant women with elevated symptoms of depression should not
      be excluded from lifestyle interventions. TRIAL REGISTRATION: ISRCTN89971375 .
      Registered 28 November 2008.

PMID- 30227834
TI  - Correction to: Daphnane diterpenes inhibit the metastatic potential of B16F10
      murine melanoma cells in vitro and in vivo.
AB  - ?.

PMID- 30227836
TI  - Detection of PIK3/AKT pathway in Moroccan population with triple negative breast
      cancer.
AB  - BACKGROUND: Triple Negative Breast Cancer (TNBC) is an aggressive form of breast
      cancer, that represents 10-20% of all breast carcinomas and characterized by the
      lack of a specific cell surface marker compared to other breast cancer subtypes.
      Due to the absence of molecular markers for TNBC his treatment options remains
      limited, without proven targeted therapies, which emphasize the need for
      discovering molecular markers that could be targeted for patient treatment, An
      important number of TNBC cases harbor aberrations in the phosphoinositide 3
      kinase (PI3K) pathway, leading to constitutive activation of the downstream
      signaling pathway. Among mechanisms of PI3K enhancement, PIK3CA mutations are
      most frequently (~ 30%) observed, along with protein loss of PTEN and AKT
      activation by phosphorylation (pAkt). Therefore, we propose to analyze
      clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in
      Moroccan triple negative breast cancer patients. METHODS: We conducted a
      retrospective study of 39 patients diagnosed with triple negative breast cancer
      between early 2013 and 2016. In this study, we used the Ion Personal Genome
      Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions
      from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of
      TNBC subtype from Moroccan patients and to correlate the results with clinical
      pathologic data. RESULTS: All patients were female with a median age of 46 years
      from (34-65). Most patients have had invasive ductal carcinoma (84.6%) and 69.2%
      of them were grade III SBR. Among the 39, 9 were right sided tumor patients and
      the remaining 30 were left-sided. Mutational analysis of PIK3CA gene was achieved
      in all TNBC patients. PIK3CA hotspot mutations were detected in 5/39 of TNBC
      (13%), in detail, among these 5 TNBC patients, one harbored mutation in exons 9
      and four in exon 20. CONCLUSION: The PI3KCA gene is highly activated and plays a
      crucial role in the pathogenesis of TNBC more, therefore, may be a potential
      therapeutic target to improve outcomes in patients.

PMID- 30227837
TI  - Comparison of the indocyanine green dye method versus the combined method of
      indigo carmine blue dye with indocyanine green fluorescence imaging for sentinel
      lymph node biopsy in breast conservative therapy for stage <=IIA breast cancer.
AB  - BACKGROUND: Fluorescence imaging (FI) is one of the methods to identify sentinel
      lymph nodes (SLNs). However, the procedure is technically complicated and
      requires procedural skills, as SLN biopsy must be conducted in dim light
      conditions. As an improved version of this method, we introduced a combined
      method (Combined mixed dye and fluorescence; CMF) consisting of indigo carmine
      blue dye and FI. The direct visualization of SLNs under shadowless surgical light
      conditions is facilitated by the addition of the blue dye. We compared the SLN
      detection rates of CMF with that of the indocyanine green (ICG) dye method (ICG
      D). METHODS: A total of 202 patients with stage <=IIA breast cancer who underwent
      breast conservative therapy with separate incision from January 2004 to February
      2017 were reviewed. Details of the two methods are as follows: (1) ICG-D: 10 mg
      of ICG was used and the green-stained SLNs were resected via a 3-4 cm axillary
      incision; (2) CMF: A combination of 5 mg of ICG and 4-8 mg of indigo carmine was
      used. After a 1.5-2 cm incision was made near the point of disappearance of the
      fluorescence using Photodynamic Eye (PDE), the blue-stained SLNs were resected
      under shadowless surgical light conditions. RESULTS: There were 92 ICG-D and 110
      CMF cases. CMF resulted in a significantly higher SLN detection rate than ICG-D
      (96.4% vs. 83.7%; p = 0.003). This difference was particularly notable in those
      aged >=60 years (98.3% vs. 74.3%) and individuals with body mass index (BMI) >=25
      kg/m2 (90.3% vs. 58.3%). CONCLUSION: CMF is an effective method to identify SLNs
      which is safe and efficient. CMF achieves a high SLN identification rate and most
      of this procedure is feasible under shadowless surgical light conditions. CMF can
      reliably perform SLN biopsy even in those aged >=60 years and individuals with
      BMI >= 25 kg/m2.

PMID- 30227838
TI  - The predictive value of preoperative neutrophil-lymphocyte ratio (NLR) on the
      recurrence of the local pigmented villonodular synovitis of the knee joint.
AB  - BACKGROUND: To explore and evaluate the predictive value of preoperative
      Neutrophil-lymphocyte ratio (NLR) on the recurrence of pigmented villonodular
      synovitis (PVNS) of the knee joint treated by arthroscopic surgery combining
      local radiotherapy. METHODS: Sixty pathological-proven PVNS cases of the knee
      joint in our department from April 2006 to March 2017 were included. All of them
      are treated by arthroscopic synovectomy combined with adjuvant radiotherapy. The
      pre-operative hematological indexes such as c-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), NLR, Platelet-lymphocyte ratio (PLR) and Lymphocyte
      monocyte ratio (LMR) were collected retrospectively and their relationship with
      postoperative recurrence was analyzed by using univariate and multivariate
      analysis, the receiver operating characteristic curves (ROC curve), the Kappa
      correspondence test and the Mc Nemar Chi-square test. RESULTS: All 60 patients
      were followed up for a median of 52.8 months (7-138 months) and the recurrence
      rate is about 23.3% (14/60). There is a significant difference in NLR between the
      recurrent and non-recurrent group (P = 0.002). It had a certain correlation with
      postoperative recurrence (correlation coefficient r = 0.438, P = 0.001). The
      optimal thresholds in ROC curve were 2.42 (sensitivity 71.4%, specificity 78.3%
      respectively). which had predictive ability for recurrence after arthroscopic
      treatment. CONCLUSION: The preoperative NLR is an easy and cost-effective
      predictor for relapse in PVNS of the knee joint after the arthroscopic surgery
      combined with local radiotherapy, which is of profound significance to guide
      clinical work.

PMID- 30227835
TI  - Diagnostic role of circulating extracellular matrix-related proteins in non-small
      cell lung cancer.
AB  - BACKGROUND: Interactions between cancer cells and the surrounding
      microenvironment are crucial determinants of cancer progression. During this
      process, bi-directional communication among tumor cells and cancer associated
      fibroblasts (CAF) regulate extracellular matrix (ECM) deposition and remodeling.
      As a result of this dynamic process, soluble ECM proteins can be released into
      the bloodstream and may represent novel circulating biomarkers useful for cancer
      diagnosis. The aim of the present study was to measure the levels of three
      circulating ECM related proteins (COL11A1, COL10A1 and SPARC) in plasma samples
      of lung cancer patients and in healthy heavy-smokers controls and test whether
      such measurements have diagnostic or prognostic value. METHODS: Gene expression
      profiling of lung fibroblasts isolated from paired normal and cancer tissue of
      NSCLC patients was performed by gene expression microarrays. The prioritization
      of the candidates for the study of circulating proteins in plasma was based on
      the most differentially expressed genes in cancer associated fibroblasts. Soluble
      ECM proteins were assessed by western blot in the conditioned medium of lung
      fibroblasts and by ELISA assays in plasma samples. RESULTS: Plasma samples from
      lung cancer patients and healthy heavy-smokers controls were tested for levels of
      COL11A1 and COL10A1 (n = 57 each) and SPARC (n = 90 each). Higher plasma levels
      of COL10A1 were detected in patients (p <= 0.001), a difference that was driven
      specifically by females (p < 0.001). No difference in COL11A1 levels between
      patients and controls was found. SPARC levels were also higher in plasma patients
      than controls (p < 0.001) with good performance in discriminating the two groups
      (AUC = 0.744). No significant association was observed between plasma proteins
      levels and clinicopathological features or survival. CONCLUSION: Soluble factors
      related to proficient tumor-stroma cross-talk are detectable in plasma of primary
      lung cancer patients and may represent a valuable complementary diagnostic tool
      to discriminate lung cancer patients from healthy heavy-smokers individuals as
      shown for the SPARC protein.

PMID- 30227839
TI  - Should sagittal osteotomy line be parallel to tibial posterior slope in high
      tibial osteotomy?
AB  - BACKGROUND: The reason why the osteotomy line in the sagittal view should be
      parallel to the medial tibial posterior slope in open wedge high tibial osteotomy
      (OWHTO) remains unclear. In addition, previous study reported that a
      posterolateral hinge position led to an increase in tibial posterior slope (TPS)
      after OWHTO. Our aims were to examine the relationships between angles among the
      tibial plateau and osteotomy planes or the hinge point and the change in TPS, and
      the location of the hinge position after OWHTO using three-dimensional computed
      tomography (3DCT). We hypothesized that the sagittal angle between the tibial
      plateau and osteotomy planes with an anterior-widening proximal tibial fragment
      resulted in increased TPS, and the hinge position located posterolaterally.
      METHODS: Preoperative planning anticipated a weight-bearing line ratio of 62% on
      the radiograph. The anterior gap was 67% of the posterior gap in OWHTO. We
      identified the tibial plateau and upper and lower osteotomy planes on 3DCT of 82
      patients with symptomatic medial osteoarthritic knee after OWHTO. The osteotomy
      plane angles between the tibial plateau and upper osteotomy planes, and opening
      gap angles between both osteotomy planes in the coronal and sagittal views were
      measured. The anteroposterior (AP) and lateral hinge position was displayed as a
      percentage on the upper osteotomy plane. We assessed the relationships among
      them. RESULTS: The TPS significantly increased after OWHTO (p = 0.002). There was
      no significant difference between the sagittal osteotomy plane angle and the
      change in TPS. The sagittal opening gap angle and the AP hinge position ratio
      were significantly correlated with the change in the TPS (r = 0.477 p < 0.001 and
      r = - 0.342, p = 0.002, respectively). The hinge position was located a mean of
      16.0% from the lateral and 48.6% from the posterior tibial edge in the upper
      osteotomy plane. CONCLUSIONS: Contrary to our expectation, the osteotomy plane
      did not need to be parallel to the tibial plateau plane in the sagittal view.
      However, the osteotomy gap should be rectangular in the sagittal view. The hinge
      position located nearly in the center of the sagittal view.

PMID- 30227840
TI  - Long-term psychiatric inpatients' perspectives on weight gain, body satisfaction,
      diet and physical activity: a mixed methods study.
AB  - BACKGROUND: Obesity is a significant problem for people with serious mental
      illness. We aimed to consider body size from the perspective of long-stay
      psychiatric inpatients, focussing on: weight gain and its causes and impacts;
      diet and physical activity; and the perceived ability to make meaningful change
      in these domains. METHOD: A mixed methods study with 51 long-term psychiatric
      forensic and rehabilitation inpatients using semi-structured interviews combined
      with biometric and demographic data. RESULTS: 94% of participants were overweight
      or obese (mean BMI 35.3, SD 8.1). They were concerned about their weight, with
      75% of them attempting to lose weight. Qualitative responses indicated low
      personal effectiveness and self-stigmatisation. Participants viewed their weight
      gain as something 'done to them' through medication, hospitalisation and leave
      restrictions. A prevailing theme was that institutional constraints made it
      difficult to live a healthy life (just the way the system is). Many had an
      external locus of control, viewing weight loss as desirable but unachievable,
      inhibited by environmental factors and requiring a quantum of motivation they
      found hard to muster. Despite this, participants were thoughtful and interested,
      had sound ideas for weight loss, and wished to be engaged in a shared endeavour
      to achieve better health outcomes. Consulting people as experts on their
      experiences, preferences, and goals may help develop new solutions, remove
      unidentified barriers, and improve motivation. CONCLUSIONS: The importance of an
      individualised, multifactorial approach in weight loss programmes for this group
      was clear. Patient-led ideas and co-design should be key principles in programme
      and environmental design.

PMID- 30227842
TI  - Translation of nutrient recommendations into personalized optimal diets for
      Chinese urban lactating women by linear programming models.
AB  - BACKGROUND: Lactating women need to consume a high-quality diet to replete
      nutrient stores depleted during pregnancy and to ensure sufficient nutrition for
      breastfeeding. However, several studies reported suboptimal dietary quality and
      nutrient intake of lactating mothers in China. The objectives of this study was
      to apply dietary modeling method to develop individualized optimal diets, which
      meet the nutrient requirements for lactating women in urban China. METHODS: Data
      were collected from a sample of 576 lactating women from 0 to 240 days postpartum
      during the Maternal Infant Nutrition Growth study conducted between 2011 and 2012
      in three cities including Beijing, Guangzhou, and Suzhou. Dietary intake data
      were collected with an interviewer-administered 24-h survey. Linear programming
      was applied to develop dietary plans that meet recommendations for lactation
      women in the China Dietary Reference Intakes 2013 and the Chinese Dietary
      Guideline 2016, while with least deviation from the observed dietary intake.
      RESULTS: Through dietary modeling, individual optimal diets were developed for
      576 lactating women. The optimal diets met all the food and nutrient intake
      constraints set in the linear programming models. The large difference between
      observed and optimized diets suggests that the nutrient needs of lactating
      mothers in China may only be met after substantial dietary changes. In addition,
      the analysis showed that it was difficult to meet the recommended intake for six
      nutrients: vitamin A, vitamin B1, vitamin B6, calcium, selenium, and dietary
      fiber. Moreover, four clusters in the optimized diets were identified by K-means
      cluster analysis. The four clusters confirmed that the optimal diets developed by
      linear programming could characterize the variety in dietary habits by
      geographical regions and duration of lactation. CONCLUSION: Linear programming
      could help translate nutrient recommendations into personal diet advices for a
      sample of urban lactating mothers from China. The study showed that dietary
      modeling is helpful to support healthy eating of lactation women by translating
      dietary guidelines into personalized meal plans. TRIAL REGISTRATION: The Maternal
      Infant Nutrition Growth study was registered in ClinicalTrials.gov with
      identifier NCT01971671 . Registration date October 29, 2013.

PMID- 30227843
TI  - Factors influencing early withdrawal from a drug and alcohol treatment program
      and client perceptions of successful recovery and employment: a qualitative
      study.
AB  - BACKGROUND: Substance use disorders are a major contributor to the economic and
      healthcare burden in Australia. Therapeutic communities (TCs) are utilised
      treatment methods globally, though low program completion rates continue to
      represent a major obstacle in effective and sustainable drug and alcohol
      treatment. The aim of this study was to explore reasons for early withdrawal from
      TC programs and perceptions of successful recovery. This study also aimed to
      explore how employment and volunteering related to early exit and perceptions of
      successful recovery. METHODS: Semi-structured qualitative interviews were
      conducted with 13 ex-residents from a long-term TC program at a community-based
      rehab organisation in regional Australia. RESULTS: Thematic analysis revealed a
      complex interplay of factors contributing to early TC withdrawal, and perceptions
      of successful recovery from a lived experience perspective and how this was
      shaped by employment and volunteering. Eleven themes were identified. Three
      relating to reasons for joining the program, which connected with ultimate
      withdrawal from the program: Pre-program existing relationships, pre-program
      employment situation and needing a 'circuit breaker' in their life. Three
      relating to reasons for early withdrawal: TC program characteristics,
      relationships during the program and planning future employment. Five relating to
      perceptions of successful recovery: Improved understanding of their addiction,
      reduced substance use, improved physical and psychological health, relationship
      success and employment success. CONCLUSIONS: Reasons for leaving treatment early
      are multi-faceted and revolve around relationships, planning future employment
      and program characteristics. The influence that each plays on their decision to
      leave early is varied and determined by the value they assign it. Perceived
      success extends far beyond achieving and maintaining abstinence to encompass
      improved relationships, psychological and physical wellbeing, understanding of
      addiction and employment, studying or volunteering. Self-worth and feeling able
      to contribute to society through employment, study and volunteering were
      perceived to be essential elements of successful recovery. Clinicians, policy
      makers and program developers should use the extended definition of successful
      recovery from the ex-clients perspective when determining the clinical and
      economic effectiveness of TC programs.

PMID- 30227841
TI  - Pain coping skills training for African Americans with osteoarthritis study:
      baseline participant characteristics and comparison to prior studies.
AB  - BACKGROUND: The Pain Coping Skills Training for African Americans with
      OsteoaRTthritis (STAART) trial is examining the effectiveness of a culturally
      enhanced pain coping skills training (CST) program for African Americans with
      osteoarthritis (OA). This disparities-focused trial aimed to reach a population
      with greater symptom severity and risk factors for poor pain-related outcomes
      than previous studies. This paper compares characteristics of STAART participants
      with prior studies of CST or cognitive behavioral therapy (CBT)-informed training
      in pain coping strategies for OA. METHODS: A literature search identified 10
      prior trials of pain CST or CBT-informed pain coping training among individuals
      with OA. We descriptively compared characteristics of STAART participants with
      other studies, in 3 domains of the National Institutes of Minority Health and
      Health Disparities' Research Framework: Sociocultural Environment (e.g., age,
      education, marital status), Biological Vulnerability and Mechanisms (e.g, pain
      and function, body mass index), and Health Behaviors and Coping (e.g., pain
      catastrophizing). Means and standard deviations (SDs) or proportions were
      calculated for STAART participants and extracted from published manuscripts for
      comparator studies. RESULTS: The mean age of STAART participants, 59 years (SD =
      10.3), was lower than 9 of 10 comparator studies; the proportion of individuals
      with some education beyond high school, 75%, was comparable to comparator studies
      (61-86%); and the proportion of individuals who are married or living with a
      partner, 42%, was lower than comparator studies (62-66%). Comparator studies had
      less than about 1/3 African American participants. Mean scores on the Western
      Ontario and McMaster Universities Osteoarthritis Index pain and function scales
      were higher (worse) for STAART participants than for other studies, and mean body
      mass index of STAART participants, 35.2 kg/m2 (SD = 8.2), was higher than all
      other studies (30-34 kg/m2). STAART participants' mean score on the Pain
      Catastrophizing scale, 19.8 (SD = 12.3), was higher (worse) than other studies
      reporting this measure (7-17). CONCLUSIONS: Compared with prior studies with
      predominantly white samples, STAART participants have worse pain and function and
      more risk factors for negative pain-related outcomes across several domains.
      Given STAART participants' high mean pain catastrophizing scores, this sample may
      particularly benefit from the CST intervention approach. TRIAL REGISTRATION:
      NCT02560922.

PMID- 30227845
TI  - Prevalence and factors associated with female genital mutilation among women of
      reproductive age in the Bawku municipality and Pusiga District of northern Ghana.
AB  - BACKGROUND: Globally, three million girls are at risk of female genital
      mutilation (FGM) and an estimated 200 million girls and women in the world have
      undergone FGM. While the overall prevalence of FGM in Ghana is 4%, studies have
      shown that the overall prevalence in the Upper East Region is 38%, with Bawku
      municipality recording the highest at 82%. METHODS: This study used a cross
      sectional design with a quantitative approach: a survey with women of
      reproductive age (15-49). RESULTS: Among all respondents, 830 women who
      participated in the study, 61% reported having undergone FGM. Of those
      circumcised, 66% indicated their mothers influenced it. Three quarters of the
      women think FGM could be stopped through health education. Women who live in the
      Pusiga district (AOR: 1.66; 95% CI: 1.16-2.38), are aged 35-49 (AOR: 4.24; 95%
      CI: 2.62-6.85), and have no formal education (AOR: 2.78; 95% CI: 1.43-5.43) or
      primary education (AOR: 2.10; 95% CI: 1.03-4.31) were more likely to be
      circumcised relative to those who reside in Bawku Municipal, are aged 15-24, and
      had tertiary education. Likewise, married women (AOR: 3.82; 95% CI: 2.53-5.76)
      were more likely to have been circumcised compared with unmarried women. At a
      site-specific level, factors associated with FGM included age and marital status
      in Bawku, and age, marital status, and women's education in Pusiga. CONCLUSION:
      Female Genital Mutilation is still being practiced in the Bawku Municipality and
      the Pusiga District of northern Ghana, particularly among women with low socio
      economic status. Implementing interventions that would provide health education
      to communities and promote girl-child education beyond the primary level could
      help end the practice.

PMID- 30227844
TI  - Extracellular matrix collagen I promotes the tumor progression of residual
      hepatocellular carcinoma after heat treatment.
AB  - BACKGROUND: Accelerated malignant behaviors induced by insufficient thermal
      ablation have been increasingly reported, however, the exact mechanisms are still
      unclear. Here, we investigated the importance of the extracellular matrix (ECM)
      in modulating the progression of residual hepatocellular carcinoma (HCC) after
      heat treatment. METHODS: Heat-exposed residual HCC cells were cultured in
      different ECM gels. We used basement membrane gel (Matrigel) to simulate the
      normal microenvironment and collagen I to model the pathological stromal ECM. The
      alterations of morphology and parameters of proliferation, epithelial-mesenchymal
      transition (EMT) and stemness were analyzed in vitro and in vivo. RESULTS:
      Increased collagen I deposition was observed at the periablational zone after
      incomplete RFA of HCC in a xenograft model. The markers of cell proliferation,
      EMT, motility and progenitor-like traits of heat-exposed residual HCC cells were
      significantly induced by collagen I as compared to Matrigel (p values all <
      0.05). Importantly, collagen I induced the activation of ERK phosphorylation in
      heat-exposed residual HCC cells. ERK1/2 inhibitor reversed the collagen I
      promoted ERK phosphorylation, cell proliferative, protrusive and spindle-like
      appearance of heat-treated residual HCC cells in vitro. Moreover, collagen I
      promoted the in vivo tumor progression of heat-exposed residual HCC cells, and
      sorafenib markedly reversed the collagen I-mediated protumor effects.
      CONCLUSIONS: Our findings demonstrate that collagen I could enhance the
      aggressive progression of residual HCC cells after suboptimal heat treatment and
      sorafenib may be a treatment approach to thwart this process.

PMID- 30227846
TI  - Genome-wide identification of tissue-specific long non-coding RNA in three farm
      animal species.
AB  - BACKGROUND: Numerous long non-coding RNAs (lncRNAs) have been identified and
      their roles in gene regulation in humans, mice, and other model organisms
      studied; however, far less research has been focused on lncRNAs in farm animal
      species. While previous studies in chickens, cattle, and pigs identified lncRNAs
      in specific developmental stages or differentially expressed under specific
      conditions in a limited number of tissues, more comprehensive identification of
      lncRNAs in these species is needed. The goal of the FAANG Consortium (Functional
      Annotation of Animal Genomes) is to functionally annotate animal genomes,
      including the annotation of lncRNAs. As one of the FAANG pilot projects, lncRNAs
      were identified across eight tissues in two adult male biological replicates from
      chickens, cattle, and pigs. RESULTS: Comprehensive lncRNA annotations for the
      chicken, cattle, and pig genomes were generated by utilizing RNA-seq from eight
      tissue types from two biological replicates per species at the adult
      developmental stage. A total of 9393 lncRNAs in chickens, 7235 lncRNAs in cattle,
      and 14,429 lncRNAs in pigs were identified. Including novel isoforms and lncRNAs
      from novel loci, 5288 novel lncRNAs were identified in chickens, 3732 in cattle,
      and 4870 in pigs. These transcripts match previously known patterns of lncRNAs,
      such as generally lower expression levels than mRNAs and higher tissue
      specificity. An analysis of lncRNA conservation across species identified a set
      of conserved lncRNAs with potential functions associated with chromatin structure
      and gene regulation. Tissue-specific lncRNAs were identified. Genes proximal to
      tissue-specific lncRNAs were enriched for GO terms associated with the tissue of
      origin, such as leukocyte activation in spleen. CONCLUSIONS: LncRNAs were
      identified in three important farm animal species using eight tissues from adult
      individuals. About half of the identified lncRNAs were not previously reported in
      the NCBI annotations for these species. While lncRNAs are less conserved than
      protein-coding genes, a set of positionally conserved lncRNAs were identified
      among chickens, cattle, and pigs with potential functions related to chromatin
      structure and gene regulation. Tissue-specific lncRNAs have potential regulatory
      functions on genes enriched for tissue-specific GO terms. Future work will
      include epigenetic data from ChIP-seq experiments to further refine these
      annotations.

PMID- 30227848
TI  - 3D electroanatomical mapping is less sensitive to atrial remodeling in estimation
      of true left atrial volume than echocardiography.
AB  - BACKGROUND: Left atrial (LA) enlargement has been identified as a predictor of
      worse clinical outcome after catheter ablation for atrial fibrillation (AF). We
      investigated the correspondence of LA size parameters assessed by
      echocardiography, CT and 3D electroanatomical mapping in patients with AF treated
      by catheter ablation. METHODS: We analyzed echocardiographic LA volume
      measurements by disc summation method (LAVDISC), computed tomography (LAVCT) and
      3D electroanatomical mapping (LAVCARTO) in 100 pts. (71% males; aged 63 +/- 8
      years; paroxysmal AF in 55% of patients). RESULTS: Mean LAVDISC was 83 +/- 25 ml
      (median: 115; IQR: 98-140 ml), mean LAVCT was 120 +/- 34 ml (median: 115; IQR: 98
      140 ml) and mean LAVCARTO was 123 +/- 36 ml (median: 118; IQR: 99-132 ml).
      Pearson's correlation coefficient between LAVDISC a LAVCT was 0.6 (p < 0.0001)
      and between LAVCARTO and LAVCT was 0.79 (p < 0.0001). There was a significant
      difference between the two correlation coefficients (p < 0.004). The absolute
      difference between LAVCARTO and LAVCT (3.5 (95% CI -42 - 43) ml) was
      significantly lower (p < 0.0001) as compared to LAVDISC and LAVCT (- 39 (95% CI 
      102 - 24) ml). In opposite to LAVDISC, the bias between LAV obtained by CT and
      CARTO did not differentiate according to presence of spherical remodeling (1.7 +/
      28 vs. vs. 5.1 +/- 31 ml). Only presence of sinus rhythm was significant and
      independent covariate of the difference between CARTO and CT-derived LAVs by
      multivariate regression analysis. CONCLUSIONS: Even though LA volumes evaluated
      by 3D-electroanatomical mapping have quite good accuracy, the precision is low.
      For volumes estimated by echocardiography, both precision and accuracy are low.

PMID- 30227847
TI  - Genomic characterization of three novel Basilisk-like phages infecting Bacillus
      anthracis.
AB  - BACKGROUND: In the present study, we sequenced the complete genomes of three
      novel bacteriophages v_B-Bak1, v_B-Bak6, v_B-Bak10 previously isolated from
      historical anthrax burial sites in the South Caucasus country of Georgia. We
      report here major trends in the molecular evolution of these phages, which we
      designate as "Basilisk-Like-Phages" (BLPs), and illustrate patterns in their
      evolution, genomic plasticity and core genome architecture. RESULTS: Comparative
      whole genome sequence analysis revealed a close evolutionary relationship between
      our phages and two unclassified Bacillus cereus group phages, phage Basilisk, a
      broad host range phage (Grose JH et al., J Vir. 2014;88(20):11846-11860) and
      phage PBC4, a highly host-restricted phage and close relative of Basilisk (Na H.
      et al. FEMS Microbiol. letters. 2016;363(12)). Genome comparisons of phages v_B
      Bak1, v_B-Bak6, and v_B-Bak10 revealed significant similarity in sequence, gene
      content, and synteny with both Basilisk and PBC4. Transmission electron
      microscopy (TEM) confirmed the three phages belong to the Siphoviridae family. In
      contrast to the broad host range of phage Basilisk and the single-strain
      specificity of PBC4, our three phages displayed host specificity for Bacillus
      anthracis. Bacillus species including Bacillus cereus, Bacillus subtilis,
      Bacillus anthracoides, and Bacillus megaterium were refractory to infection.
      CONCLUSIONS: Data reported here provide further insight into the shared genomic
      architecture, host range specificity, and molecular evolution of these rare B.
      cereus group phages. To date, the three phages represent the only known close
      relatives of the Basilisk and PBC4 phages and their shared genetic attributes and
      unique host specificity for B. anthracis provides additional insight into
      candidate host range determinants.

PMID- 30227849
TI  - Marathons and myasthenia gravis: a case report.
AB  - BACKGROUND: The cardinal symptoms of auto-immune myasthenia gravis are fatigue
      and weakness. Endurance events such as marathon running would seem incompatible
      with this chronic disease. Many patients stop sport altogether. There is limited
      literature of patients with auto-immune myasthenia gravis undergoing regular
      endurance exercise. CASE PRESENTATION: We report the case of a 36-year-old female
      who began long-distance running whilst experiencing initial symptoms of
      myasthenia gravis. She was diagnosed with auto-immune myasthenia gravis and
      whilst advised to stop all sport, her way of fighting and living with this
      chronic and unpredictable disease was to continue running to maintain a healthy
      body and mind. Despite suffering from ocular, bulbar and localized limb
      fatigability, she managed to complete multiple marathons and achieve disease
      stability with cholinesterase inhibitors. CONCLUSIONS: Marathon and half-marathon
      running lead to distinct changes in mediators of inflammation in an exercise-dose
      dependent manner. Despite symptoms of weakness and fatigue in certain muscles in
      myasthenia gravis, physical exertion remains possible and may not worsen symptoms
      as demonstrated in this case and recent studies. The immunomodulatory role of
      exercise could be considered in this case however this hypothesis remains to be
      confirmed in future studies with quantitative data.

PMID- 30227851
TI  - Paediatric massage for treatment of acute diarrhoea in children: a meta-analysis.
AB  - BACKGROUND: Massage therapy has been used by many traditional Chinese medicine
      physicians to treat acute diarrhoea in children. Since no relevant systematic
      reviews assessed the clinical effectiveness or the risk of massage therapy, in
      this study, a meta-analysis was conducted to evaluate the efficacy of paediatric
      massage for the treatment of acute diarrhoea in children. METHODS: In this meta
      analysis, paediatric patients who were diagnosed with acute diarrhoea were
      included. Interventions using massage therapy alone or combined with other non
      pharmacological approaches were included, while in the control groups, patients
      received pharmacotherapy. The primary outcome was clinical effective rate. Seven
      databases were used in our research, and the following search terms were used:
      (massage OR tui na OR manipulation OR acupressure) AND (infant OR child OR baby
      OR paediatrics) AND (diarrhoea OR diarrhoea) AND (randomized controlled trial).
      The search date was up to April 30, 2018. RESULTS: A total of 26 studies
      encompassing 2644 patients were included in this meta-analysis. It was shown that
      paediatric massage was significantly better than pharmacotherapy in treating
      acute diarrhoea in children in terms of clinical effective rate (n = 2213, RR =
      1.20, 95% CI: 1.14 to 1.27), clinical cure rate (n = 345, RR = 1.37, 95% CI: 1.19
      to 1.57), and cure time (n = 513, MD = - 0.77, 95% CI: -0.89 to - 0.64). However,
      the quality of evidence for this finding was low due to high risk of bias of the
      included studies. CONCLUSIONS: The present work supported paediatric massage in
      treating acute diarrhoea in children. More well-designed randomized controlled
      trials are still needed to further evaluate the efficacy of paediatric massage.

PMID- 30227850
TI  - The kinome of pineapple: catalog and insights into functions in crassulacean acid
      metabolism plants.
AB  - BACKGROUND: Crassulacean acid metabolism (CAM) plants use water 20-80% more
      efficiently by shifting stomata opening and primary CO2 uptake and fixation to
      the nighttime. Protein kinases (PKs) play pivotal roles in this biological
      process. However, few PKs have been functionally analyzed precisely due to their
      abundance and potential functional redundancy (caused by numerous gene
      duplications). RESULTS: In this study, we systematically identified a total of
      758 predicted PK genes in the genome of a CAM plant, pineapple (Ananas comosus).
      The pineapple kinome was classified into 20 groups and 116 families based on the
      kinase domain sequences. The RLK was the largest group, containing 480 members,
      and over half of them were predicted to locate at the plasma membrane. Both
      segmental and tandem duplications make important contributions to the expansion
      of pineapple kinome based on the synteny analysis. Ka/Ks ratios showed all of the
      duplication events were under purifying selection. The global expression analysis
      revealed that pineapple PKs exhibit different tissue-specific and diurnal
      expression patterns. Forty PK genes in a cluster performed higher expression
      levels in green leaf tip than in white leaf base, and fourteen of them had strong
      differential expression patterns between the photosynthetic green leaf tip and
      the non-photosynthetic white leaf base tissues. CONCLUSIONS: Our findings provide
      insights into the evolution and biological function of pineapple PKs and a
      foundation for further functional analysis of PKs in CAM plants. The gene
      duplication, expression, and coexpression analysis helped us to rapidly identify
      the key candidates in pineapple kinome, which may play roles in the carbon
      fixation process in pineapple and help engineering CAM pathway into C3 crops for
      improved drought tolerance.

PMID- 30227853
TI  - Integrating patient safety education into early medical education utilizing
      cadaver, sponges, and an inter-professional team.
AB  - BACKGROUND: Introducing patient safety and quality improvement science to medical
      students is integral to improving healthcare. However, developing and
      implementing a patient safety curriculum can be challenging in a medical school
      curriculum that is already densely packed. Our aim was to develop and evaluate
      the impact of a workshop introducing patient safety and quality improvement
      science to a large class of first-year medical students. METHOD: As a part of an
      evolving longitudinal patient safety curriculum, an introductory workshop on
      patient safety was integrated into an anatomy course. A high impact event (a
      simulated "retained sponge" discovery during an anatomy dissection lab) was used
      to introduce medical error. The educational session which followed consisted of a
      presentation by an interprofessional team utilizing the retained sponge as
      example of an error. Use of safety tools was introduced and quality improvement
      science was discussed using the evolution of methods to decrease retained foreign
      objects during surgery. A patient's story told by a close family member about the
      personal impact of medical errors was presented. Students then participated in an
      interactive breakout activity and completed a module on safety. The impact of the
      workshop was assessed through pre- and post- session tests. RESULTS: Quantitative
      and qualitative evaluation reflected a positive effect of the session in
      improving students' safety knowledge and attitudes. Students' mean total
      knowledge improved from 7.58 to 8.98 (p = 0.000). Mean total attitudes score
      improved from 47.73 to 50.56 (p = 0.000). Students' comments after the workshop
      reflected increased awareness and appreciation of the importance of addressing
      medical errors. CONCLUSION: A workshop introducing patient safety and quality
      improvement to first year medical students improved knowledge and attitudes
      regarding safety and increased awareness of the importance of addressing medical
      errors in their future careers. Integrating patient safety education into an
      existing foundational science course is a model for teaching patient safety at
      other medical schools.

PMID- 30227852
TI  - Trichosporon inkin meningitis in Northeast Brazil: first case report and review
      of the literature.
AB  - BACKGROUND: Trichosporon species may colonize the skin, respiratory tract and
      gastrointestinal tract of human beings. The yeast is recognized as etiological
      agent of white piedra, a superficial mycosis. Nevertheless, immunocompromised
      hosts may develop invasive Trichosporonosis. Central nervous system
      trichosporonosis is a very rare clinical manifestation. In fact, only a few cases
      have been published in the literature and none of them was caused by Trichosporon
      inkin. CASE PRESENTATION: Here we report the first clinical case of
      meningoencephalitis due to this species in a female previously healthy patient
      under corticosteroids and antibiotics therapy for several months. She was
      submitted to an invasive procedure to remove a left sided acoustic neuroma and
      further developed a cerebrospinal fistula. After some days of the procedure, she
      presented a predominantly and intensive occipital holocranial headache, followed
      by vomiting, hyporexia, weight loss, asthenia, irritability, difficulty to
      concentrate and rotator vertigo. The patient further developed a cerebrospinal
      fistula in the occipital region and was submitted to a surgical correction. After
      several months of clinical interventions, she was diagnosed with CNS
      Trichosporonosis, after Magnetic Resonance Imaging and positive microbiological
      cultures obtained within two different occasions (2 weeks apart). Despite the
      antifungal therapy with Amphotericin B and Voriconazole, the patient did not
      survive. CONCLUSIONS: Despite CNS Fungal infections are mostly due to
      Cryptococcus spp., other emergent yeasts, such as T. inkin may be considered as a
      likely etiological agent. This is the first case report of CNS Trichosporonosis,
      where species identification was performed with rDNA sequencing.

PMID- 30227854
TI  - A two-stage inversion technique for total auricular reconstruction: case report
      and literature review.
AB  - BACKGROUND: The reconstruction of a total amputated auricle is aesthetically
      demanding for otorhinolaryngology surgeons. Although various reattachment methods
      have been introduced since 1898, only a few have achieved satisfactory aesthetic
      outcomes. This study aimed to present a successful case of auricular
      reconstruction using a two-stage inversion technique. CASE PRESENTATION: The
      patient's left ear was extensively lacerated in a violent event 3 h before
      admission. The first-stage surgery was performed within 6 h of ischemic time. The
      amputated segment was prepared and trimmed carefully, and the anterior aspect of
      the avulsed auricle was directly sutured. The posterior skin of the ear was
      separated from the cartilage to close the wound. Then, using an inversion
      maneuver, the cartilage was pushed into a postauricular underlying muscle bed. In
      the second-stage surgery 27 days after the first procedure, the auricle was
      released and the normal ear structure was restored using full-thickness skin
      grafting. During a follow-up of more than 9 years, the patient showed
      satisfactory postoperative results in terms of cosmetic and functional outcomes
      of the reattached auricle. The size of his left ear was about 90% of the size of
      his right ear. CONCLUSIONS: The reconstruction of a total amputated auricle is
      challenging. The key to surgery lies in the sufficient preservation of the
      meticulous shape of the cartilage. The microsurgical anastomosis is a good choice
      only in selected cases. It is believed that the two-stage inversion technique can
      be a simple alternative to reconstruct the auricle in most situations when it is
      lacerated and contaminated.

PMID- 30227856
TI  - Comparative analysis of predictive methods for early assessment of compliance
      with continuous positive airway pressure therapy.
AB  - BACKGROUND: Patients suffering obstructive sleep apnea are mainly treated with
      continuous positive airway pressure (CPAP). Although it is a highly effective
      treatment, compliance with this therapy is problematic to achieve with serious
      consequences for the patients' health. Unfortunately, there is a clear lack of
      clinical analytical tools to support the early prediction of compliant patients.
      METHODS: This work intends to take a further step in this direction by building
      compliance classifiers with CPAP therapy at three different moments of the
      patient follow-up, before the therapy starts (baseline) and at months 1 and 3
      after the baseline. RESULTS: Results of the clinical trial shows that month 3 was
      the time-point with the most accurate classifier reaching an f1-score of 87% and
      84% in cross-validation and test. At month 1, performances were almost as high as
      in month 3 with 82% and 84% of f1-score. At baseline, where no information of
      patients' CPAP use was given yet, the best classifier achieved 73% and 76% of f1
      score in cross-validation and test set respectively. Subsequent analyzes carried
      out with the best classifiers of each time point revealed baseline factors (i.e.
      headaches, psychological symptoms, arterial hypertension and EuroQol visual
      analog scale) closely related to the prediction of compliance independently of
      the time-point. In addition, among the variables taken only during the follow-up
      of the patients, Epworth and the average nighttime hours were the most important
      to predict compliance with CPAP. CONCLUSIONS: Best classifiers reported high
      performances after one month of treatment, being the third month when significant
      differences were achieved with respect to the baseline. Four baseline variables
      were reported relevant for the prediction of compliance with CPAP at each time
      point. Two characteristics more were also highlighted for the prediction of
      compliance at months 1 and 3. TRIAL REGISTRATION: ClinicalTrials.gov Identifier,
      NCT03116958 . Retrospectively registered on 17 April 2017.

PMID- 30227857
TI  - Attitudes to prenatal screening among Norwegian citizens: liberality, ambivalence
      and sensitivity.
AB  - BACKGROUND: Norway's liberal abortion law allows for abortion on social
      indications, yet access to screening for fetal abnormalities is restricted.
      Norwegian regulation of, and public discourse about prenatal screening and
      diagnosis has been exceptional. In this study, we wanted to investigate whether
      the exceptional regulation is mirrored in public attitudes. METHOD: An electronic
      questionnaire with 11 propositions about prenatal screening and diagnosis was
      completed by 1617 Norwegian adults (response rate 8.5%). RESULTS: A majority of
      respondents supports increased access to prenatal screening with ultrasound (60%)
      and/or full genome sequencing of fetal DNA (55%) available for all pregnant
      women. Significant minorities indicate, however, that a public offer of prenatal
      screening for all pregnant women would signal that people with Down syndrome are
      unwanted (46%) or could be criticized for contributing to a 'sorting society'
      (48%). CONCLUSIONS: Results indicate deeper ambivalences and a cultural
      sensitivity to the ethical challenges of prenatal screening and subsequent
      abortions. The specific diagnosis of Down syndrome and the fear of becoming a
      'sorting society' which sorts human life due to diagnoses, appear to play
      prominent roles in citizen deliberations. The low response rate means that a non
      response bias cannot be excluded, yet reasons why results are still likely to be
      of value are discussed.

PMID- 30227855
TI  - Practical issues in clinical scenarios involving CKD patients requiring
      antithrombotic therapy in light of the 2017 ESC guideline recommendations.
AB  - BACKGROUND: The choice of the most appropriate antithrombotic regimen that
      balances ischemic and bleeding risks was addressed by the August 2017 European
      Society of Cardiologists (ESC)/European Association for Cardio-Thoracic Surgery
      Focused Update recommendations, which propose new evaluation scores and protocols
      for patients requiring a coronary stent or patients with an acute coronary
      syndrome, atrial fibrillation, or a high bleeding risk and indication for oral
      anticoagulation therapy. DISCUSSION: Numerous questions remain regarding
      antithrombotic regimens and risk management algorithms for both ischemic and
      hemorrhagic events in patients with chronic kidney disease (CKD) in various
      clinical scenarios. Limitations of current studies include a general ack of
      advanced CKD patients in major randomized controlled trials, of evidence on
      algorithm implementation, and of robust assessment tools for hemorrhagic risk.
      Herein, we aim to analyze the ESC Update recommendations and the newly
      implemented risk scores (DAPT, PRECISE-DAPT, PARIS) from the point of view of
      CKD, providing suggestions on drug choice (which combination has the best
      evidence), dosage, and duration (the same or different as for non-CKD population)
      of antithrombotics, as well as to identify current shortcomings and to envision
      directions of future research. CONCLUSION: We provide an evidence-based
      perspective on the new proposed bleeding management protocol, with focus on the
      CKD population. Despite previous important steps on antithrombotic therapy of
      renal patients, there remain many unsolved questions for which our suggestions
      could fundament new randomized controlled trials and specific protocols.

PMID- 30227858
TI  - Netrin-1 attenuates brain injury after middle cerebral artery occlusion via
      downregulation of astrocyte activation in mice.
AB  - BACKGROUND: Netrin-1 functions largely via combined receptors and downstream
      effectors. Evidence has shown that astrocytes express netrin-1 receptors,
      including DCC and UNC5H2. However, whether netrin-1 influences the function of
      astrocytes was previously unknown. METHODS: Lipopolysaccharide was used to
      stimulate the primary cultured astrocytes; interleukin release was used to track
      astrocyte activation. In vivo, shRNA and netrin-1 protein were injected in the
      mouse brain. Infarct volume, astrocyte activation, and interleukin release were
      used to observe the function of netrin-1 in neuroinflammation and brain injury
      after middle cerebral artery occlusion. RESULTS: Our results demonstrated that
      netrin-1 reduced lipopolysaccharide-induced interleukin-1beta and interleukin
      12beta release in cultured astrocytes, and blockade of the UNC5H2 receptor with
      an antibody reversed this effect. Additionally, netrin-1 increased p-AKT and PPAR
      gamma expression in primary cultured astrocytes. In vivo studies showed that
      knockdown of netrin-1 increased astrocyte activation in the mouse brain after
      middle cerebral artery occlusion (p < 0.05). Moreover, injection of netrin-1
      attenuated GFAP expression (netrin-1 0.27 +/- 0.06 vs. BSA 0.62 +/- 0.04, p <
      0.001) and the release of interleukins and reduced infarct volume after brain
      ischemia (netrin-1 0.27 +/- 0.06 vs. BSA 0.62 +/- 0.04 mm3, p < 0.05).
      CONCLUSION: Our results indicate that netrin-1 is an important molecule in
      regulating astrocyte activation and neuroinflammation in cerebral ischemia and
      provides a potential target for ischemic stroke therapy.

PMID- 30227859
TI  - "I attend at Vanguard and I attend here as well": barriers to accessing
      healthcare services among older South Africans with HIV and non-communicable
      diseases.
AB  - BACKGROUND: HIV and non-communicable disease (NCD) are syndemic within sub
      Saharan Africa especially among older persons. The two epidemics interact with
      one another within a context of poverty, inequality and inequitable access to
      healthcare resulting in an increase in those aged 50 and older living with HIV
      and experiencing an NCD co-morbidity. We explore the challenges of navigating
      healthcare for older persons living with HIV and NCD co-morbidity. METHODS: In
      depth semi-structured interviews were conducted with a small sample of older
      persons living with HIV (OPLWH). The perspectives of key informants were also
      sought to triangulate the evidence of OPLWH. The research took place in two
      communities on the outskirts of Cape Town, South Africa. All interviews were
      conducted by a trained interviewer and transcribed and translated for analysis.
      Thematic content analysis guided data analysis. RESULTS: OPLWH experienced an HIV
      NCD syndemic. Our respondents sought care and accessed treatment for both HIV and
      other chronic (and acute) conditions, though these services were provided at
      different health facilities or by different health providers. Through the
      syndemic theory, it is possible to observe that OPLWH and NCDs face a number of
      physical and structural barriers to accessing the healthcare system. These
      barriers are compounded by separate appointments and spaces for each condition.
      These difficulties can exacerbate the impact of their ill-health and perpetuate
      structural vulnerabilities. Despite policy changes towards integrated care, this
      is not the experience of OPLWH in these communities. CONCLUSIONS: The population
      living with HIV is aging increasing the likelihood that those living with HIV
      will also be living with other chronic conditions including NCDs. Thus, it is
      essential that health policy address this basic need to integrate HIV and NCD
      care.

PMID- 30227862
TI  - Comparative mechanical analysis of deep brain stimulation electrodes.
AB  - The new field of neuro-prosthetics focuses on the design and implementation of
      neural prostheses to restore some of the lost neural functions. The electrode
      tissue contacts remain one of the major obstacles of neural prostheses
      microstructure. Recently, Microelectrode fabrication techniques have been
      developed to have a long-term and stable interface with the brain. In this paper,
      a comparative analysis of finite element models (FEM) for several electrode
      layouts is conducted. FEM involves parametric and sensitivity analysis to show
      the effects of the different design parameters on the electrode mechanical
      performance. These parameters include electrode dimensions, geometry, and
      materials. The electrodes mechanical performance is evaluated with various
      analysis techniques including: linear buckling analysis, stationary analysis with
      axial and shear loading, and failure analysis for brittle and ductile materials.
      Finally, a novel figure of merit (FOM) is presented and dedicated to the various
      electrodes prototypes. The proposed designs take into account mechanical
      performance, fabrication cost, and cross sectional area of the electrode. The FOM
      provides important design insights to help the electrodes designers to select the
      best electrode design parameters that meet their design constraints.

PMID- 30227861
TI  - Perceptions of the acceptability and feasibility of reducing occupational
      sitting: review and thematic synthesis.
AB  - BACKGROUND: Reducing workplace sedentary behaviour (sitting) is a topic of
      contemporary public health and occupational health interest. Understanding
      workers' perspectives on the feasibility and acceptability of strategies, and
      barriers and facilitators to reducing workplace sitting time, can help inform the
      design and implementation of targeted interventions. The aim of this qualitative
      synthesis was to identify and synthesise the evidence on factors perceived to
      influence the acceptability and feasibility of reducing sitting at work, without,
      and with, an associated intervention component. METHODS: A systematic search of
      the peer-reviewed literature was conducted across multiple databases in October
      2017 to identify studies with a qualitative component relating to reducing
      workplace sitting time. Relevant data were extracted and imported into NVivo, and
      analysed by three of the authors by coding the results sections of papers line-by
      line, with codes organised into sub-themes and then into overarching themes.
      Studies with and without an associated intervention were analysed separately.
      RESULTS: Thirty-two studies met the inclusion criteria, 22 of which had collected
      qualitative data during and/or following a workplace intervention. Sample sizes
      ranged from five through to 71 participants. Studies predominately involved desk
      based workers (28/32) and were most frequently conducted in Australia, USA or the
      United Kingdom (26/32). Similar themes were identified across non-intervention
      and intervention studies, particularly relating to barriers and facilitators to
      reducing workplace sitting. Predominately, work and social environment attributes
      were identified as barriers/facilitators, with desk-based work and work pressures
      influencing the perceived feasibility of reducing sitting, particularly for low
      cost interventions. Support from co-workers and managers was considered a key
      facilitator to reducing sitting, while social norms that discouraged movement
      were a prominent barrier. Across all studies, some consistent perceptions of
      benefits to reducing sitting were identified, including improved physical health,
      enhanced emotional well-being and associated work-related benefits. CONCLUSION:
      Common barriers and facilitators to reducing workplace sitting time were
      identified across the literature, most prominently involving the social
      environment and job-related demands. These findings can inform the design and
      implementation of workplace sitting reduction strategies. To increase the
      generalisability of findings, further research is needed in a more diverse range
      of countries and industries.

PMID- 30227860
TI  - Genetic variant in CXCL12 gene raises susceptibility to HPV infection and
      squamous intraepithelial lesions development: a case-control study.
AB  - BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted
      virus in women worldwide. The persistence of the virus may cause warts that are
      considered benign lesions and low or high grade intraepithelial lesions
      (LSIL/HSIL). Immunological system plays an important role in the resolution of
      infections. In this context, we highlight the chemokines, which are important
      regulators in the development of viral infections and inflammation. Among which
      CXCL12 stands out, due to its pro-inflammatory features, acting as
      chemoattractant recruiting immune cells. Several polymorphisms were identified in
      CXCL12 gene including rs1801157 in the 3'-untranslated region, which is
      characterized by a substitution of a guanine for an adenine. METHODS: In this
      study, 195 women were classified as HPV non-infected and 169 as HPV-infected. HPV
      DNA was detected by polymerase chain reaction (PCR) and the polymorphism was
      assessed in blood cells through restriction fragment length polymorphism
      analysis. RESULTS: HPV infection was more incident in women who had more than 4
      sexual partners during lifetime (p = 0.007), among those who presented lower
      number of pregnancies (p = 0.017). HPV was more prevalent among allele A carriers
      confirmed by logistic regression analysis adjusted for several confounding
      factors [ORADJ = 4.985; CI95% (2.85-8.72), p < 0.001]. An association between
      allele A carriers and HSIL development (p = 0.003) was also observed.
      CONCLUSIONS: In the present study, we demonstrated that CXCL12 rs1801157 is
      independently associated with HPV infection and exerts influence in HSIL
      development, suggesting it as a promising susceptibility biomarker for HPV
      infection and lesions development.

PMID- 30227863
TI  - The piRNA pathway responds to environmental signals to establish
      intergenerational adaptation to stress.
AB  - BACKGROUND: piRNAs have a constitutive role in genome defence by silencing
      transposable elements in the germline. In the nematode Caenorhabditis elegans,
      piRNAs also induce epigenetic silencing of transgenes, which can be maintained
      for many generations in the absence of the piRNA pathway. The role of multi
      generational epigenetic inheritance in adaptation to the environment is unknown.
      RESULTS: Here, we show that piRNA biogenesis is downregulated in response to a
      small increase in temperature. Some effects on gene expression persist into
      subsequent generations and are associated with a negative fitness cost. We show
      that simultaneous infection with pathogenic bacteria suppresses downregulation of
      the piRNA pathway in response to increased temperature. This effect is associated
      with increased fitness of progeny of infected animals in subsequent generations.
      CONCLUSIONS: Our results show that the piRNA pathway integrates inputs from the
      environment to establish intergenerational responses to environmental conditions,
      with important consequences for the fitness of the subsequent generation.

PMID- 30227865
TI  - Changes in cardiac volume determined with repeated enhanced 4DCT during
      chemoradiotherapy for esophageal cancer.
AB  - BACKGROUND: Concurrent chemoradiotherapy is considered curative intent treatment
      for patients with non-operative esophageal cancer. Radiation-induced heart damage
      receives much attention. We performed repeated four-dimensional computed
      tomography (4DCT) to detect changes in cardiac volume during radiotherapy for
      esophageal cancer patients, and explored potential factors responsible for those
      changes. METHODS: Forty-six patients with esophageal cancer underwent enhanced
      4DCT and three-dimensional (3D) CT scans before radiotherapy and every 10
      fractions during treatment. The heart was contoured on 3DCT images, 4DCT end
      expiratory (EE) images and 4DCT maximum intensity projection (MIP) images by the
      same radiation oncologist. Heart volumes and other relative parameters were
      compared by the SPSS software package, version 19.0. RESULTS: Compared with its
      initial value, heart volume was smaller at the 10th fraction (reduction = 3.27%,
      4.45% and 4.52% on 3DCT, EE and MIP images, respectively, p < 0.05) and the 20th
      fraction (reduction = 6.05%, 5.64% and 4.51% on 3DCT, EE and MIP images,
      respectively, p < 0.05), but not at the 30th fraction. Systolic and diastolic
      blood pressures were reduced (by 16.95 +/- 16.69 mmHg and 7.14 +/- 11.64 mmHg,
      respectively, both p < 0.05) and the heart rate was elevated by 5.27 +/- 6.25
      beats/min (p < 0.05) after radiotherapy. None of the potential explanatory
      variables correlated with heart volume changes. CONCLUSIONS: Cardiac volume
      reduced significantly from an early treatment stage and maintained the reduction
      until the middle stage. The heart volume changes observed on 3DCT and 4DCT were
      consistent during radiotherapy. The changes in heart volume, blood pressure and
      heart rate may be valuable indicators of cardiac impairment and target dose
      changes.

PMID- 30227864
TI  - Home-based transcranial direct current stimulation plus tracking training therapy
      in people with stroke: an open-label feasibility study.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is an effective
      neuromodulation adjunct to repetitive motor training in promoting motor recovery
      post-stroke. Finger tracking training is motor training whereby people with
      stroke use the impaired index finger to trace waveform-shaped lines on a monitor.
      Our aims were to assess the feasibility and safety of a telerehabilitation
      program consisting of tDCS and finger tracking training through questionnaires on
      ease of use, adverse symptoms, and quantitative assessments of motor function and
      cognition. We believe this telerehabilitation program will be safe and feasible,
      and may reduce patient and clinic costs. METHODS: Six participants with
      hemiplegia post-stroke [mean (SD) age was 61 (10) years; 3 women; mean (SD) time
      post-stroke was 5.5 (6.5) years] received five 20-min tDCS sessions and finger
      tracking training provided through telecommunication. Safety measurements
      included the Digit Span Forward Test for memory, a survey of symptoms, and the
      Box and Block test for motor function. We assessed feasibility by adherence to
      treatment and by a questionnaire on ease of equipment use. We reported
      descriptive statistics on all outcome measures. RESULTS: Participants completed
      all treatment sessions with no adverse events. Also, 83.33% of participants found
      the set-up easy, and all were comfortable with the devices. There was 100%
      adherence to the sessions and all recommended telerehabilitation. CONCLUSIONS:
      tDCS with finger tracking training delivered through telerehabilitation was safe,
      feasible, and has the potential to be a cost-effective home-based therapy for
      post-stroke motor rehabilitation. TRIAL REGISTRATION: NCT02460809
      (ClinicalTrials.gov).

PMID- 30227866
TI  - Effect of dose rate on pulmonary toxicity in patients with hematolymphoid
      malignancies undergoing total body irradiation.
AB  - BACKGROUND: This study evaluated the effect of radiation dose rate in patients
      with hematolymphoid malignancies undergoing myeloablative conditioning with total
      body irradiation (TBI), for hematopoietic stem cell transplantation. METHODS: The
      incidence of pulmonary toxicity (PT) and treatment efficacy were compared between
      the conventional (>= 6 cGy/min) and reduced dose rate (< 6 cGy/min). Seventy
      seven patients receiving once-daily TBI between 2000 and 2016 were reviewed. We
      compared the cumulative rate of PT, overall survival (OS), relapse, and
      transplantation-related mortality (TRM) between conventional (n = 54) and reduced
      (n = 23) groups. Factors associated with PT were assessed in the presence of
      competing risks. RESULTS: The median follow-up time was 40.7 months, and PT
      occurred in 50 patients (64.9%). On multivariate analyses, the groups classified
      by the dose rate (P = 0.010), total dose (P = 0.025), and conditioning regimen (P
      = 0.029) were significant factors for the development of PT. OS was significantly
      reduced when PT occurred (P < 0.001). However, the OS, relapse, and TRM were not
      different between the two groups. CONCLUSIONS: In summary, about two-thirds of
      the patients undergoing daily TBI experienced PT, which affected OS. Therefore,
      reducing the dose rate (less than 6 cGy/min) of TBI can decrease the risk of PT,
      without compromising the treatment efficacy.

PMID- 30227867
TI  - Breast cancer risk factors, survival and recurrence, and tumor molecular subtype:
      analysis of 3012 women from an indigenous Asian population.
AB  - BACKGROUND: Limited evidence, mostly from studies in Western populations,
      suggests that the prognostic effects of lifestyle-related risk factors may be
      molecular subtype-dependent. Here, we examined whether pre-diagnostic lifestyle
      related risk factors for breast cancer are associated with clinical outcomes by
      molecular subtype among patients from an understudied Asian population. METHODS:
      In this population-based case series, we evaluated breast cancer risk factors in
      relation to 10-year all-cause mortality (ACM) and 5-year recurrence by molecular
      subtype among 3012 women with invasive breast cancer in Sarawak, Malaysia. A
      total of 579 deaths and 314 recurrence events occurred during a median follow-up
      period of ~ 24 months. Subtypes (luminal A-like, luminal B-like, HER2-enriched,
      triple-negative) were defined using immunohistochemical markers for hormone
      receptors and human epidermal growth factor receptor 2 (HER2) in conjunction with
      histologic grade. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the
      associations between risk factors and ACM/recurrence were estimated in subtype
      specific Cox regression models. RESULTS: We observed heterogeneity in the
      relationships between parity/breastfeeding, age at first full-term pregnancy
      (FFP), family history, body mass index (BMI), and tumor subtype (p value < 0.05).
      Among luminal A-like patients only, older age at menarche [HR (95% CI) >=15 vs <=
      12 years = 2.28 (1.05, 4.95)] and being underweight [HRBMI < 18.5kg/m2vs. 18.5
      24.9kg/m2 = 3.46 (1.21, 9.89)] or overweight [HR25-29.9kg/m2vs. 18.5-24.9kg/m2=
      3.14 (1.04, 9.50)] were associated with adverse prognosis, while
      parity/breastfeeding [HRbreastfeeding vs nulliparity = 0.48 (0.27, 0.85)] and
      older age at FFP [HR > 30 vs < 21 years = 0.20 (0.04, 0.90)] were associated with
      good prognosis. For these women, the addition of age at menarche,
      parity/breastfeeding, and BMI, provided significantly better fit to a prognostic
      model containing standard clinicopathological factors alone [LRchi2 (8df) =
      21.78; p value = 0.005]. Overall, the results were similar in relation to
      recurrence. CONCLUSIONS: Our finding that breastfeeding and BMI were associated
      with prognosis only among women with luminal A-like breast cancer is consistent
      with those from previously published data in Western populations. Further
      prospective studies will be needed to clarify the role of lifestyle modification,
      especially changes in BMI, in improving clinical outcomes for women with luminal
      A-like breast cancer.

PMID- 30227868
TI  - Genome sequencing of rice subspecies and genetic analysis of recombinant lines
      reveals regional yield- and quality-associated loci.
AB  - BACKGROUND: Two of the most widely cultivated rice strains are Oryza sativa
      indica and O. sativa japonica, and understanding the genetic basis of their
      agronomic traits is of importance for crop production. These two species are
      highly distinct in terms of geographical distribution and morphological traits.
      However, the relationship among genetic background, ecological conditions, and
      agronomic traits is unclear. RESULTS: In this study, we performed the de novo
      assembly of a high-quality genome of SN265, a cultivar that is extensively
      cultivated as a backbone japonica parent in northern China, using single-molecule
      sequencing. Recombinant inbred lines (RILs) derived from a cross between SN265
      and R99 (indica) were re-sequenced and cultivated in three distinct ecological
      conditions. We identify 79 QTLs related to 15 agronomic traits. We found that
      several genes underwent functional alterations when the ecological conditions
      were changed, and some alleles exhibited contracted responses to different
      genetic backgrounds. We validated the involvement of one candidate gene, DEP1, in
      determining panicle length, using CRISPR/Cas9 gene editing. CONCLUSIONS: This
      study provides information on the suitable environmental conditions, and genetic
      background, for functional genes in rice breeding. Moreover, the public
      availability of the reference genome of northern japonica SN265 provides a
      valuable resource for plant biologists and the genetic improvement of crops.

PMID- 30227869
TI  - The factors of deterioration in long-term clinical course of lumbar spinal canal
      stenosis after successful conservative treatment.
AB  - BACKGROUND: The treatment of lumbar spinal canal stenosis (LSS) depends on
      symptom severity. In the absence of severe symptoms such as severe motor
      disturbances or bowel and/or urinary dysfunction, conservative treatment is
      generally the first choice for the treatment of LSS. However, we experienced
      cases of worsening symptoms even after successful conservative treatment. The
      purpose of this study is to investigate the long-term clinical course of LSS
      following successful conservative treatment and analyze the prognostic factors
      associated with symptom deterioration. METHODS: The study included 60 LSS
      patients (34 females and 26 males) whose symptoms were relieved by conservative
      treatment between April 2007 and March 2010 and who were followed up for 5 years
      or longer. The mean age at admission was 64.8 +/- 8.5 years (range, 40-85 years
      old), and the mean follow-up period was 7.3 years (range, 5.8-9.5 years). We
      defined "deterioration" of symptoms as the shortening of intermittent
      claudication more than 50 m compared with those at discharge or the occurrence or
      progression of lower limb paralysis, and "poor outcome" as the deterioration
      within 5 years after discharge. The long-term outcome of conservative treatment
      for LSS was analyzed by Kaplan-Meier analysis. Furthermore, logistic regression
      analysis was performed to reveal the risk factors of poor outcome for clinical
      classification, severe intermittent claudication (<= 100 m), lower limb muscle
      weakness, vertebral body slip (>= 3 mm), scoliosis (Cobb angle >= 10 degrees ),
      block on myelography, and redundant nerve roots of the cauda equina. RESULTS:
      Thirty-four (56.7%) patients preserved their condition at discharge during the
      follow-up, whereas 26 patients (43.3%) showed deterioration. Sixteen patients had
      a decreased intermittent claudication distance, and 10 patients had newly
      developed or progressive paralysis. The probability of preservation was
      maintained at 68.3% at 5 years after discharge. Logistic regression analysis
      demonstrated that only severe intermittent claudication (<= 100 m) was a
      significant risk factor of a poor outcome (p = 0.005, odds ratio = 6.665).
      CONCLUSIONS: The patients with severe intermittent claudication should be
      carefully followed up because those are the significant deterioration candidates
      despite the success in conservative treatment.

PMID- 30227870
TI  - miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast
      growth factor 9 (FGF9) and cyclin D2 (CCND2).
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of death
      worldwide. MicroRNAs (miRNAs) have been indicated as crucial actors in cancer
      biology. Accumulating evidence suggests that miRNAs can be used as diagnostic and
      prognostic markers for NSCLC. METHODS: The purpose of this study was to
      characterize and identify the novel biomarker miR-4317 and its targets in NSCLC.
      The expression of miR-4317 was analyzed by in situ hybridization (ISH) and
      quantitative reverse transcription polymerase chain reaction (qRT-PCR). The
      effect of miR-4317 on proliferation was evaluated through 3-4,5-dimethylthiazol-2
      yl-5-3-carboxymethoxyphenyl-2-4-sulfophenyl-2H-tetrazolium (MTS) and colony
      formation assays, and cell migration and invasion were evaluated through
      transwell assays. The expression of target proteins and downstream molecules was
      analyzed by qRT-PCR and western blot. Dual-luciferase reporter assay was used to
      assess the target genes of miR4317 in NSCLC cells. RESULTS: Our results
      demonstrated that miR-4317 was downregulated in NSCLC tissues and serum,
      particularly in lymph node metastasis and advanced clinical stage tissues. Kaplan
      Meier survival analysis showed that NSCLC patients with high expression of miR
      4317 exhibited better overall survival (OS). Enhanced expression of miR-4317
      significantly inhibited proliferation, colony formation, migration and invasion,
      and hampered cycles of NSCLC cell lines in vitro. Our results suggested that miR
      4317 functions by directly targeting fibroblast growth factor 9 (FGF9) and cyclin
      D2 (CCND2). In concordance with in vitro studies, mouse xenograft, lung, and
      brain metastatic studies validated that miR-4317 functions as a potent suppressor
      miRNA of NSCLC in vivo. Systemically delivered agomiR-4317 reduced tumor growth
      and inhibited FGF9 and CCND2 protein expression. Reintroduction of FGF9 and CCND2
      attenuated miR-4317-mediated suppression of migration and invasion in NSCLC.
      CONCLUSIONS: Our results indicate that miR-4317 can reduce NSCLC cell growth and
      metastasis by targeting FGF9 and CCND2. These findings provide new evidence of
      miR-4317 as a potential non-invasive biomarker and therapeutic target for NSCLC.

PMID- 30227871
TI  - Pharmacological inhibition of LSD1 activity blocks REST-dependent medulloblastoma
      cell migration.
AB  - BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor in
      children. Current problems in the clinic include metastasis, recurrence, and
      treatment-related sequelae that highlight the need for targeted therapies.
      Epigenetic perturbations are an established hallmark of human MB and expression
      of Lysine Specific Demethylase 1 (LSD1) is elevated in MBs compared to normal
      tissue, suggesting that LSD1 inhibitors may have efficacy against human MB
      tumors. METHODS: Expression of LSD1 was examined across a publicly-available
      database and correlated with patient outcomes. Sonic Hedgehog (SHH) MB samples
      were clustered based on expression of LSD1 and LSD1-associated RE-1 silencing
      transcription factor (REST) target genes as well as genes involved in metastasis.
      Resulting clusters were examined for patient outcomes associated with LSD1 and
      REST expression. Human SHH MB cell lines were transduced with a REST-transgene to
      create isogenic cell pairs. In vitro viability and cell migration assays were
      used to examine the effect of LSD1 knockdown or inhibition on these parameters.
      RESULTS: We demonstrate that subsets of SHH MB tumors have elevated LSD1
      expression coincident with increased expression of its deubiquitylase, USP7, and
      REST. Patients with co-elevation of USP7, REST, and LSD1 have poorer outcomes
      compared to those with lower expression of these genes. In SHH MB cell lines,
      REST elevation increased cell growth and LSD1 protein levels. Surprisingly, while
      genetic loss of LSD1 reduced cell viability, pharmacological targeting of its
      activity using LSD1 inhibitors did not affect cell viability. However, a
      reduction in REST-dependent cell migration was seen in wound healing, suggesting
      that REST-LSD1 interaction regulates cell migration. Ingenuity pathway analyses
      validated these findings and identified Hypoxia Inducible Factor 1 alpha (HIF1A)
      as a potential target. In line with this, ectopic expression of HIF1A rescued the
      loss of migration seen following LSD1 inhibition. CONCLUSIONS: A subset of SHH
      patients display increased levels of LSD1 and REST, which is associated with poor
      outcomes. REST elevation in MB in conjunction with elevated LSD1 promotes MB cell
      migration. LSD1 inhibition blocks REST-dependent cell migration of MB cells in a
      HIF1A-dependent manner.

PMID- 30227872
TI  - Leadership experiences and practices of South African health managers: what is
      the influence of gender? -a qualitative, exploratory study.
AB  - BACKGROUND: The importance of strong and transformative leadership is recognised
      as essential to the building of resilient and responsive health systems. In this
      regard, Sustainable Development Goals (SDG) 5 prioritises a current gap, by
      calling for women's full and effective participation and equal opportunities for
      leadership, including in the health system. In South Africa, pre-democracy
      repressive race-based policies, coupled with strong patriarchy, led to women and
      especially black women, being 'left behind' in terms of career development and
      progression into senior health leadership positions. METHODS: Given limited prior
      inquiry into this subject, we conducted a qualitative exploratory study employing
      case study design, with the individual managers as the cases, to examine the
      influence of gender on career progression and leadership perceptions and
      experiences of senior managers in South Africa in five geographical districts,
      located in two provinces. We explored this through in-depth interviews, including
      life histories, career pathway mapping and critical incident analysis. The study
      sample selection was purposive and included 14 female and 5 male senior-managers
      in district and provincial health departments. RESULTS: Our findings suggest that
      women considerably lag behind their male counterparts in advancing into
      management- and senior positions. We also found that race strongly intersected
      with gender in the lived experiences and career pathways of black female managers
      and in part for some black male managers. Professional hierarchy further
      compounded the influence of gender and race for black women managers, as doctors,
      who were frequently male, advanced more rapidly into management and senior
      management positions, than their female counterparts. Although not widespread,
      other minority groups, such as male managers in predominantly female departments,
      also experienced prejudice and marginalisation. Affirmative employment policies,
      introduced in the new democratic dispensation, addressed this discriminatory
      legacy and contributed to a number of women being the 'first' to occupy senior
      management positions. In one of the provinces, these pioneering female managers
      assumed role-modelling and mentoring roles and built strong networks of support
      for emerging managers. This was aided by an enabling, value-based, organisational
      culture. CONCLUSION: This study has implications for institutionalising personal
      and organisational development that recognise and appropriately advances women
      managers, paying attention to the intersections of gender, race and professional
      hierarchy. It is important in the context of national and global goals, in
      particular SDG 5, that women and in particular black women, are prioritised for
      training and capacity development and ensuring that transformative health system
      policies and practices recognise and adapt, supporting the multiple social and
      work roles that managers, in particular women, play.

PMID- 30227873
TI  - Regulation of ATP levels in Escherichia coli using CRISPR interference for
      enhanced pinocembrin production.
AB  - BACKGROUND: Microbial biosynthesis of natural products holds promise for
      preclinical studies and treating diseases. For instance, pinocembrin is a natural
      flavonoid with important pharmacologic characteristics and is widely used in
      preclinical studies. However, high yield of natural products production is often
      limited by the intracellular cofactor level, including adenosine triphosphate
      (ATP). To address this challenge, tailored modification of ATP concentration in
      Escherichia coli was applied in efficient pinocembrin production. RESULTS: In the
      present study, a clustered regularly interspaced short palindromic repeats
      (CRISPR) interference system was performed for screening several ATP-related
      candidate genes, where metK and proB showed its potential to improve ATP level
      and increased pinocembrin production. Subsequently, the repression efficiency of
      metK and proB were optimized to achieve the appropriate levels of ATP and
      enhancing the pinocembrin production, which allowed the pinocembrin titer
      increased to 102.02 mg/L. Coupled with the malonyl-CoA engineering and
      optimization of culture and induction condition, a final pinocembrin titer of
      165.31 mg/L was achieved, which is 10.2-fold higher than control strains.
      CONCLUSIONS: Our results introduce a strategy to approach the efficient
      biosynthesis of pinocembrin via ATP level strengthen using CRISPR interference.
      Furthermore coupled with the malonyl-CoA engineering and induction condition have
      been optimized for pinocembrin production. The results and engineering strategies
      demonstrated here would hold promise for the ATP level improvement of other
      flavonoids by CRISPRi system, thereby facilitating other flavonoids production.

PMID- 30227874
TI  - Risk of reduced platelet counts in patients with nonalcoholic fatty liver disease
      (NAFLD): a prospective cohort study.
AB  - BACKGROUND: The production of peripheral platelet is mainly regulated by
      thrombopoietin, which is a glycoprotein hormone predominantly synthesized in the
      liver. Previously, many studies have reported that there was an inverse
      correlation between the degree of chronic viral hepatitis and the peripheral
      platelet count. However, the effect of nonalcoholic fatty liver disease (NAFLD)
      on the peripheral platelet counts remains unclear. METHODS: With 1303
      participants from "The prevention of MS and multi-metabolic disorders in Jiangsu
      province of China (PMMJS)" cohort study, we investigated the associations between
      NAFLD and the risk of platelet counts reduction in Chinese adults. The paired
      samples T test was used to explore the platelet counts changes between baseline
      and follow-up. Multivariate logistic regression was used to examine the
      association between presence of NAFLD and the risk of platelet reduction by
      calculating the odds ratios (ORs) and 95% confidence interval (CI). RESULTS:
      After five years of follow-up, platelet counts were markedly reduced from 220.6
      +/- 42.22 (109/L) at baseline to 208.41 +/- 40.70 (109/L) at follow-up in NAFLD
      group (P < 0.0001). However, platelet counts were slightly lowered from 213.2 +/-
      43.26(109/L) at baseline to 211.8 +/- 41.65 (109/L) at follow-up in non-NAFLD
      people (P = 0.2349). Meanwhile, there was a significant association between NAFLD
      and the risks of platelet count reduction, even after adjustment for confounding
      variables (OR: 1.68, 95% CI: 1.06-2.67). Additionally, among the participants
      with BMI <= 23 kg/m2 and SUA <= 344.3 MUmol/L, the NAFLD participants have an
      increased risk of platelet count reduction compared to the persons in non-NAFLD
      group. CONCLUSIONS: Our present results suggested that NAFLD individuals have an
      increased risk of platelet counts reduction.

PMID- 30227875
TI  - Food insecurity and self-rated health in rural Nicaraguan women of reproductive
      age: a cross-sectional study.
AB  - BACKGROUND: Access to food is a basic necessity, and food insecurity may impair
      the individual's well-being and health. Self-rated health measurements have
      frequently been used to assess population health. Little is known, however, as to
      whether food security is associated with self-rated health in low- and middle
      income settings. This study aims at analyzing the association between food
      security and self-rated health among non-pregnant women of reproductive age in a
      rural Nicaraguan setting. METHODS: Data was taken from the 2014 update of a
      health and demographic surveillance system in the municipalities of Los Cuatro
      Santos in northwestern Nicaragua. Fieldworkers interviewed women about their self
      rated health using a 5-point Likert scale. Food insecurity was assessed by the
      household food insecurity access (HFIAS) scale. A multilevel Poisson random
      intercept model was used to calculate the prevalence ratio. RESULTS: The survey
      included 5866 women. In total, 89% were food insecure, and 48% had poor self
      rated health. Food insecurity was associated with poor self-rated health, and
      remained so after adjustment for potential confounders and accounting for
      community dependency. CONCLUSION: In this Nicaraguan resource-limited setting,
      there was an association between food insecurity and poor self-rated health. Food
      insecurity is a facet of poverty and measures an important missing capability
      directly related to health.

PMID- 30227876
TI  - Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain
      and correlation with geographic origin of HCV isolates.
AB  - BACKGROUND: We evaluated the frequency of naturally occurring resistance
      associated substitutions (RASs) and their characteristic of polymorphic or non
      polymorphic amino acid change to direct acting antivirals (DAAs) in NS5b HCV
      subtypes 1a and 1b according to different geographic origin of isolates. METHODS:
      Using a public database we retrieved 738 worldwide NS5b sequences (for which was
      available the geographic origin) from HCV genotype (G)1 infected patients naive
      to DAAs. NS5b sequences clustering with G1a were more conserved in regard of RASs
      than G1b isolates, (14% vs 57% RASs, P < 0.0001). RESULTS: In G1a, RASs were
      differently distributed between isolates from Europe (24%) and USA, (12%) P =
      0.0186. In particular, 421 V associated with resistance to non-nucleoside
      inhibitor beclabuvir was polymorphic in Europe and USA, being detected in 24% and
      11% of sequences, respectively, P = 0.0140. In G1b, RASs were found in 45% of
      sequences from Europe, in 54% of isolates from USA and in 70% of sequences from
      Asia (P = 0.0051). The 316 N polymorphism was detected in 54% of Asian isolates
      and at lower frequency, in 28% of isolates from USA and in 20% of European
      sequences (P < 0.0001). CONCLUSIONS: In conclusion, a higher prevalence of RASs
      in G1b respect to G1a was found and a geographical distribution of RASs and
      polymorphic aa changes was observed in G1a as well in G1b. The clinical and
      therapeutic impact of the geographic distribution of RASs to polymerase
      inhibitors remains to be established, particularly in patients with virologic
      failure to DAAs and/or advanced liver disease.

PMID- 30227877
TI  - Imaging-based clusters in current smokers of the COPD cohort associate with
      clinical characteristics: the SubPopulations and Intermediate Outcome Measures in
      COPD Study (SPIROMICS).
AB  - BACKGROUND: Classification of COPD is usually based on the severity of airflow,
      which may not sensitively differentiate subpopulations. Using a multiscale
      imaging-based cluster analysis (MICA), we aim to identify subpopulations for
      current smokers with COPD. METHODS: Among the SPIROMICS subjects, we analyzed
      computed tomography images at total lung capacity (TLC) and residual volume (RV)
      of 284 current smokers. Functional variables were derived from registration of
      TLC and RV images, e.g. functional small airways disease (fSAD%). Structural
      variables were assessed at TLC images, e.g. emphysema and airway wall thickness
      and diameter. We employed an unsupervised method for clustering. RESULTS: Four
      clusters were identified. Cluster 1 had relatively normal airway structures;
      Cluster 2 had an increase of fSAD% and wall thickness; Cluster 3 exhibited a
      further increase of fSAD% but a decrease of wall thickness and airway diameter;
      Cluster 4 had a significant increase of fSAD% and emphysema. Clinically, Cluster
      1 showed normal FEV1/FVC and low exacerbations. Cluster 4 showed relatively low
      FEV1/FVC and high exacerbations. While Cluster 2 and Cluster 3 showed similar
      exacerbations, Cluster 2 had the highest BMI among all clusters. CONCLUSIONS:
      Association of imaging-based clusters with existing clinical metrics suggests the
      sensitivity of MICA in differentiating subpopulations.

PMID- 30227878
TI  - ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2
      diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2D), rapidly increasing to epidemic
      proportions, globally escalates cardiovascular disease risk. Although intensive
      interventions and comprehensive management of environmental risks factors for T2D
      are associated with reduced cardiovascular disease, such approaches are limited
      for individuals with high genetic T2D risk. In this study we investigated
      possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur
      patients with T2D. METHODS: 275 Uygur T2D patients and 272 non-diabetic Uygur
      individuals were enrolled as study participants. 14 ACE2 polymorphisms were
      genotyped by Matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry. RESULTS: ACE2 SNP rs1978124, rs2048683, rs2074192, rs233575,
      rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P <
      0.05). The 8 diabetic risk related ACE2 SNPs were further associated with
      diabetic related cardiovascular complications or events but exhibited
      heterogeneity as fellows: firstly, almost all diabetic risk related ACE2 SNPs
      (all P < 0.05) were associated with increased SBP except rs1978124 and rs2074192,
      while rs2074192, rs4646188 and rs879922 were associated elevated DBP (all P <
      0.05). Secondly, SNP rs4646188 was not correlated with any type of dyslipidemia
      (TRIG, HDL-C, LDL-C or CHOL), and the other 7 diabetic risk related loci were at
      least correlated with one type of dyslipidemia (all P < 0.05). In particular,
      rs879922 were simultaneously correlated with four type of dyslipidemia (all P <
      0.05). Thirdly, ACE2 SNP rs2074192 and rs879922 were associated with carotid
      arteriosclerosis stenosis (CAS) >= 50% (both P < 0.05). Fourthly, ACE2 SNP
      rs2074192, rs4240157, rs4646188 and 879922 were associated with increased MAU
      (all P < 0.05). In addition, ACE2 SNP rs2048683, rs4240157, rs4646156, rs4646188
      and rs879922 were linked to heavier LVMI (all P < 0.05), but only rs4240157,
      rs4646156 and rs4646188 were associated with lower LVEF (all P < 0.05).
      CONCLUSION: ACE2 SNP rs879922 may be a common genetic loci and optimal genetic
      susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs.

PMID- 30227879
TI  - Efficient and tumor-specific knockdown of MTDH gene attenuates paclitaxel
      resistance of breast cancer cells both in vivo and in vitro.
AB  - BACKGROUND: Drug resistance of paclitaxel (TAX), the first-line chemotherapy drug
      for breast cancer, was reported to develop in 90% of patients with breast cancer,
      especially metastatic breast cancer. Investigating the mechanism of TAX
      resistance of breast cancer cells and developing the strategy improving its
      therapeutic efficiency are crucial to breast cancer cure. METHODS AND RESULTS: We
      here report an elegant nanoparticle (NP)-based technique that realizes efficient
      breast cancer treatment of TAX. Using lentiviral vector-mediated gene knockdown,
      we first demonstrated that TAX therapeutic efficiency was closely correlated with
      metadherin (MTDH) gene expression in breast cancer cell lines. This finding was
      also supported by efficacy of TAX treatment in breast cancer patients from our
      clinical studies. Specifically, TAX treatment became more effective when MTDH
      expression was decreased in MCF-7 cancer cells by the blocking nuclear factor
      kappa B (NF-kappaB) pathway. Based on these findings, we subsequently synthesized
      a polymeric NP that could co-deliver MTDH-small interfering RNA (MTDH-siRNA) and
      TAX into the breast cancer tumors in tumor-bearing mice. The NPs were composed of
      a cationic copolymer, which wrapped TAX in the inside and adsorbed the negatively
      charged siRNA on their surface with high drug-loading efficiency and good
      stability. CONCLUSIONS: NP-based co-delivery approach can effectively knock down
      the MTDH gene both in vitro and in vivo, which dramatically inhibits breast tumor
      growth, achieving effective TAX chemotherapy treatment without overt side
      effects. This study provides a potential therapeutic strategy for the treatment
      of a wide range of solid tumors highly expressing MTDH.

PMID- 30227880
TI  - Systemic retinoids for treatment of recalcitrant IgA pemphigus.
AB  - IgA pemphigus is an exceedingly rare autoimmune blistering disorder, caused by
      IgA autoantibodies against desmosomal proteins. No treatment option has been
      found to be universally effective. The disease is often recalcitrant to oral
      steroids and immunosuppressants. Here, we describe the use of systemic retinoids
      for the treatment of recalcitrant IgA pemphigus in 3 cases. Although the use of
      acitretin has been reported before, we present for the first time the positive
      effects of alitretinoin in treatment of 2 patients with IgA pemphigus. Besides
      hyperlipoproteinaemia requiring use of hypolipidemic agents in one case,
      alitretinoin was well-tolerated and has generally a more favorable side effect
      spectrum than immunosuppressants.

PMID- 30227881
TI  - The role of microglia in processing and spreading of bioactive tau seeds in
      Alzheimer's disease.
AB  - BACKGROUND: Misfolding of microtubule-associated protein tau (MAPT) within
      neurons into neurofibrillary tangles is an important pathological feature of
      Alzheimer's disease (AD). Tau pathology correlates with cognitive decline in AD
      and follows a stereotypical anatomical course; several recent studies indicate
      that tau pathology spreads inter-neuronally via misfolded tau "seeds." Previous
      research has focused on neurons as the source of these tau seeds. However, recent
      studies as well as the data contained herein suggest that microglia, the resident
      immune cells of the central nervous system, play a direct role in the spread of
      tau pathology. METHODS: Primary adult microglia were isolated from human AD cases
      and the rTg4510 tauopathy mouse model and used for analysis of gene expression,
      tau protein by Simoa technology, and quantification of tau seeding using a highly
      sensitive fluorescence resonance energy transfer (FRET) biosensing cell line for
      tau seeding and aggregation. RESULTS: Here, we show that microglia isolated from
      both human tauopathy and AD cases and the rTg4510 tauopathy mouse model stably
      contain tau seeds, despite not synthesizing any tau. Microglia releases these tau
      seeds in vitro into their conditioned media (CM). This suggests that microglia
      have taken up tau but are incapable of entirely neutralizing its seeding
      activity. Indeed, when in vitro microglia are given media containing tau seeds,
      they reduce (but do not eliminate) tau seeding. When microglia are treated with
      inflammagens such as lipopolysaccharide (LPS), interleukin-1beta (IL1beta), tumor
      necrosis factor alpha (TNFalpha), or amyloid-beta, their ability to reduce tau
      seeding is unchanged and these factors do not induce seeding activity on their
      own. CONCLUSIONS: Overall, these data suggest that microglia have a complex role:
      they are capable of taking up and breaking down seed competent tau, but do so
      inefficiently and could therefore potentially play a role in the spread of tau
      pathology.

PMID- 30227882
TI  - Burden of albinism: development and validation of a burden assessment tool.
AB  - BACKGROUND: Albinism comprises a group of autosomal recessive diseases that are
      characterized by poor vision and a variable hypopigmentation phenotype. A
      comprehensive literature review showed that no tool can assess the burden
      experienced by individuals who present with albinism, although such a tool is
      needed and would be beneficial for clinicians and patients alike. METHOD: The
      questionnaire was devised using standardized methodology for developing and
      validating questionnaires on the quality of life of subjects according to the
      following chronological structure: conceptual phase, development phase, and then
      validation phase. A multidisciplinary working group was assembled, including
      experts on questionnaire design and development, dermatologists specializing in
      care for patients with albinism, and representatives of the Genespoir
      association. RESULTS: Based on an initial verbatim report, the workgroup compiled
      a list of items that were transcribed and reformulated into questions. During the
      validation phase, principal component analysis (PCA) was conducted on the 24
      items, which allowed the questionnaire to be reduced to 20 questions [Q]. The
      standardized regression coefficients were all greater than 0.5 for their
      corresponding factors. Based on their normalized regression coefficients, each
      group of questions was linked to one of the following four dimensions, with each
      dimension consisting of at least three questions: "Live with" (8 Q), "Daily life"
      (3 Q), "Resignation" (3 Q), and "Fear of the future" (6 Q). All dimensions
      correlated well with the overall BoA score. Cronbach's alpha was 0.92 for the
      entire BoA scale, confirming excellent internal coherence. Intradimensional
      coherences all demonstrated excellent reliability (alpha > 0.65). The BoA
      questionnaire was highly correlated with the SF12, RSES and DLQI validated
      questionnaires. This outcome confirmed the external validity. CONCLUSION: This
      questionnaire represents the first specific assessment tool for evaluating the
      burden of albinism. It is easy to use and relatively quick to complete, which
      will allow the burden to be evaluated over time with a reproducible
      questionnaire. To ensure that this questionnaire can be used by as many people as
      possible, cultural and linguistic validation in US English was conducted with the
      original French version.

PMID- 30227883
TI  - Establishing a stable, repeatable platform for measuring changes in sperm DNA
      methylation.
AB  - BACKGROUND: Several independent research groups have shown that alterations in
      human sperm methylation profiles correlate with decreased fecundity and an
      increased risk of poor embryo development. Moving these initial findings from the
      lab into a clinical setting where they can be used to measure male infertility
      though requires a platform that is stable and robust against batch effects that
      can occur between sample runs. Operating parameters must be established,
      performance characteristics determined, and guidelines set to ensure
      repeatability and accuracy. The standard for technical validation of a lab
      developed test (LDT) in the USA comes from the Clinical Laboratory Improvement
      Amendments (CLIA). However, CLIA was introduced in 1988, before the advent of
      genome-wide profiling and associated computational analysis. This, coupled with
      its intentionally general nature, makes its interpretation for epigenetic assays
      non-trivial. RESULTS: Here, we present an interpretation of the CLIA technical
      validation requirements for profiling DNA methylation and calling aberrant
      methylation using the Illumina Infinium platform (e.g., the 450HM and
      MethylationEPIC). We describe an experimental design to meet these requirements,
      the experimental results obtained, and the operating parameters established.
      CONCLUSIONS: The CLIA guidelines, although not intended for high-throughput
      assays, can be interpreted in a way that is consistent with modern epigenetic
      assays. Based on such an interoperation, Illumina's Infinium platform is quite
      amenable to usage in a clinical setting for diagnostic work.

PMID- 30227884
TI  - The effect of virtual reality-based balance training on motor learning and
      postural control in healthy adults: a randomized preliminary study.
AB  - BACKGROUND: Adults with sedentary lifestyles seem to face a higher risk of
      falling in their later years. Several causes, such as impairment of strength,
      coordination, and cognitive function, influence worsening health conditions,
      including balancing ability. Many modalities can be applied to improve the
      balance function and prevent falling. Several studies have also recorded the
      effects of balance training in elderly adults for fall prevention. Accordingly,
      the aim of this study is to define the effect of virtual reality-based balance
      training on motor learning and postural control abilities in healthy adults.
      METHODS: For this study, ten subjects were randomly allocated into either the
      conventional exercise (CON) or the virtual reality (VR) group. The CON group
      underwent physical balance training, while the VR group used the virtual reality
      system 4 weeks. In the VR group, the scores from three game modes were utilized
      to describe the effect of motor learning and define the learning curves that were
      derived with the power law function. Wilcoxon Signed Ranks Test was performed to
      analyze the postural control in five standing tasks, and data were collected with
      the help of a force plate. RESULTS: The average score was used to describe the
      effect of motor learning by deriving the mathematical models for determining the
      learning curve. Additionally, the models were classified into two exponential
      functions that relied on the aim and requirement skills. A negative exponential
      function was observed in the game mode, which requires the cognitive-motor
      function. In contrast, a positive exponential function was found in the game with
      use of only the motor skill. Moreover, this curve and its model were also used to
      describe the effect of learning in the long term and the ratio of difficulty in
      each game. In the balance performance, there was a significant decrease in the
      center of pressure parameters in the VR group, while in the CON group, there was
      a significant increase in the parameters during some foot placements, especially
      in the medio-lateral direction. CONCLUSION: The proposed VR-based training relies
      on the effect of motor learning in long-term training though different kinds of
      task training. In postural analysis, both exercise programs are emphasized to
      improve the balance ability in healthy adults. However, the virtual reality
      system can promote better outcomes to improve postural control post exercising.
      Trial registration Retrospectively registered on 25 April 2018. Trial number
      TCTR20180430005.

PMID- 30227886
TI  - A whole-blood RNA transcript-based gene signature is associated with the
      development of CTLA-4 blockade-related diarrhea in patients with advanced
      melanoma treated with the checkpoint inhibitor tremelimumab.
AB  - BACKGROUND: Anti-CTLA-4 immune checkpoint blockade is associated with immune
      related adverse events (irAEs). Grade 3-4 diarrhea/colitis is the most frequent
      irAE requiring treatment discontinuation. Predicting high-risk diarrhea/colitis
      patients may facilitate early intervention, limit irAE severity, and extend
      treatment duration. No biomarkers currently predict for anti-CTLA-4 immunotherapy
      related severe diarrhea. METHODS: Whole-blood was collected pre-treatment and 30
      days post-treatment initiation from patients with stage III or IV unresectable
      melanoma who received 15 mg/kg tremelimumab at 90 day intervals in two clinical
      trials. The discovery dataset was a phase II study that enrolled 150 patients
      between December 2005 and November 2006. The validation dataset was a phase III
      study that enrolled 210 patients between March 2006 and July 2007. RT-PCR was
      performed for 169 genes associated with inflammation, immunity, CTLA-4 pathway
      and melanoma. Gene expression was correlated with grade 0-1 versus grade 2-4
      diarrhea/colitis development. RESULTS: Pre-treatment blood obtained from the
      discovery dataset (N = 150) revealed no gene predictive of diarrhea/colitis
      development (p < 0.05). A 16-gene signature (CARD12, CCL3, CCR3, CXCL1, F5,
      FAM210B, GADD45A, IL18bp, IL2RA, IL5, IL8, MMP9, PTGS2, SOCS3, TLR9 and UBE2C)
      was identified from 30 days post-tremelimumab initiation blood that discriminated
      patients developing grade 0-1 from grade 2-4 diarrhea/colitis. The 16-gene
      signature demonstrated an AUC of 0.814 (95% CI 0.743 to 0.873, p < 0.0001),
      sensitivity 42.9%, specificity 99.2%, positive predictive value (PPV) 90.0%, and
      negative predictive value (NPV) 91.4%. In the validation dataset (N = 210), the
      16-gene signature discriminated patients developing grade 0-1 from grade 2-4
      diarrhea/colitis with an AUC 0.785 (95% CI 0.723 to 0.838, p < 0.0001),
      sensitivity 57.1%, specificity 84.4%, PPV 57.1% and NPV 84.4%. CONCLUSION: This
      study identifies a whole-blood mRNA signature predictive of a clinically relevant
      irAE in patients treated with immune checkpoint blockade. We hypothesize that
      immune system modulation induced by immune checkpoint blockade results in
      peripheral blood gene expression changes that are detectable prior to clinical
      onset of severe diarrhea. Assessment of peripheral blood gene expression changes
      in patients receiving anti-PD-1/PD-L1 immunotherapy, or combination anti-CTLA4
      and anti-PD-1/PD-L1 immunotherapy, is warranted to provide early on-treatment
      mechanistic insights and identify clinically relevant predictive biomarkers.
      TRIAL REGISTRATION: Clinicaltrials.gov , NCT00257205 , registered 22 November
      2005.

PMID- 30227885
TI  - Effects of a 15-month anti-TNF-alpha treatment on plasma levels of
      glycosaminoglycans in women with rheumatoid arthritis.
AB  - BACKGROUND: In this study, the effect of 15-month anti-tumor necrosis factor
      alpha (TNF-alpha) treatment on circulating levels of plasma sulfated
      glycosaminoglycans (GAGs) and the nonsulfated GAG hyaluronic acid (HA) in female
      rheumatoid arthritis (RA) patients was assessed. METHODS: Plasma was obtained
      from healthy subjects and RA women treated with TNF-alpha antagonists (etanercept
      or adalimumab or certolizumab pegol) in combination with methotrexate. GAGs were
      isolated from plasma samples using ion exchange low-pressure liquid
      chromatography. Total sulfated GAGs were quantified using a hexuronic acid assay.
      Plasma levels of keratan sulfate (KS) and HA were measured using immunoassay
      kits. RESULTS: Total sulfated GAGs and HA levels were higher in female RA
      patients before treatment in comparison to healthy subjects. KS levels did not
      differ between RA women and controls. Anti-TNF-alpha treatment resulted in
      normalization of plasma total GAG and HA levels in RA patients, without any
      effect on KS levels. CONCLUSIONS: Our results suggest that anti-TNF-alpha therapy
      has a beneficial effect on extracellular matrix remodeling in the course of RA.

PMID- 30227887
TI  - Does BMP2 play a role in the pathogenesis of equine degenerative suspensory
      ligament desmitis?
AB  - OBJECTIVE: Horses afflicted with degenerative suspensory ligament desmitis (DSLD)
      suffer from progressive leg pain and lameness without history of trauma. DSLD is
      a systemic disorder caused by abnormal accumulation of proteoglycans in many
      connective tissues. One proteoglycan found in higher quantities in DSLD is
      decorin. The accumulated decorin has an abnormally glycosylated glycosaminoglycan
      chain in DSLD. In addition to acellular accumulations of proteoglycans foci of
      active fibroblasts/tenoblasts were observed in some tendons and suspensory
      ligaments (SLs) from DSLD cases We have hypothesized that this represents an
      early event in DSLD and that production of chondrogenic growth factors, such as
      BMP2, and/or enzyme participating in glycosylation of glycosaminoglycans is a
      major factor in initiation and progression of DSLD. RESULTS: Using
      immunohistochemistry we have identified BMP2 in these cellular foci, indicating
      association with proteoglycan production, but not in other cells in the tendon
      and SLs. In contrast, very little staining for TGFbeta and dermatan sulfate
      epimerase, an enzyme involved in glycosylation of glycosaminoglycan chains, was
      observed in these foci and other cells in both control and DSLD-affected tendons
      and SLs. Our data support our hypothesis that chondrogenic growth factors may be
      responsible, at least in part for progression of DSLD in horses.

PMID- 30227889
TI  - Effects of mutations in the effector domain of influenza A virus NS1 protein.
AB  - OBJECTIVE: The multifunctional NS1 protein of influenza A virus has roles in
      antagonising cellular innate immune responses and promoting viral gene
      expression. To better understand the interplay between these functions, we tested
      the effects of NS1 effector domain mutations known to affect homo-dimerisation or
      interactions with cellular PI3 kinase or Trim25 on NS1 ability to promote nuclear
      export of viral mRNAs. RESULTS: The NS1 dimerisation mutant W187R retained the
      functions of binding cellular NXF1 as well as stabilising NXF1 interaction with
      viral segment 7 mRNAs and promoting their nuclear export. Two PI3K-binding
      mutants, NS1 Y89F and Y89A still bound NXF1 but no longer promoted NXF1
      interactions with segment 7 mRNA or its nuclear export. The Trim25-binding mutant
      NS1 E96A/E97A bound NXF1 and supported NXF1 interactions with segment 7 mRNA but
      no longer supported mRNA nuclear export. Analysis of WT and mutant NS1
      interaction partners identified hsp70 as specifically binding to NS1 E96A/E97A.
      Whilst these data suggest the possibility of functional links between NS1's
      effects on intracellular signalling and its role in viral mRNA nuclear export,
      they also indicate potential pleiotropic effects of the NS1 mutations; in the
      case of E96A/E97A possibly via disrupted protein folding leading to chaperone
      recruitment.

PMID- 30227890
TI  - The effect of optimised patient information materials on recruitment in a lung
      cancer screening trial: an embedded randomised recruitment trial.
AB  - BACKGROUND: Written participant information materials are important for ensuring
      that potential trial participants receive necessary information so that they can
      provide informed consent. However, such materials are frequently long and
      complex, which may negatively impact patient understanding and willingness to
      participate. Improving readability, ease of comprehension and presentation may
      assist with improved participant recruitment. The Systematic Techniques for
      Assisting Recruitment to Trials (MRC START) study aimed to develop and evaluate
      interventions to improve trial recruitment. This study aimed to assess the
      effectiveness of an optimised participant information brochure and cover letter
      developed by MRC START regarding response and participant recruitment rates.
      METHODS: We conducted a study within a trial (SWAT) embedded in the EarlyCDT Lung
      Cancer Scotland (ECLS) trial that aimed to assess the effectiveness of a new test
      in reducing the incidence of patients with late-stage lung cancer at diagnosis
      compared with standard care. Potential participants approached for ECLS were
      randomised to receive the original participant information brochure and
      accompanying letter (control group) or optimised versions of these materials
      which had undergone user testing and a process of re-writing, re-organisation and
      professional graphic design (intervention group). The primary outcome was the
      number of patients recruited to ECLS. The secondary outcome was the proportion of
      patients expressing an interest in participating in ECLS. RESULTS: In total, 2262
      patients were randomised, 1136 of whom were sent the intervention materials and
      1126 of whom were sent the control materials. The proportion of patients enrolled
      and randomised into ECLS was 180 of 1136 (15.8%) in the intervention group and
      176 of 1126 (15.6%) in the control group (OR = 1.016, 95% CI, 0.660 to 1.564).
      The proportion of patients who positively responded to the invitation was 224 of
      1136 (19.7%) in the intervention group and 205 of 1126 (18.2%) in the control
      group (OR = 1.103, 95% CI, 0.778 to 1.565). CONCLUSIONS: Optimised patient
      information materials made little difference to the proportion of patients
      positively responding to a trial invitation or to the proportion subsequently
      randomised to the host trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01925625
      . Registered on 15 August 2015. Study Within A Trial, SWAT-23. Registered on 12
      April 2016.

PMID- 30227888
TI  - Vulnerability and resilience to Alzheimer's disease: early life conditions
      modulate neuropathology and determine cognitive reserve.
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      with a high prevalence among the elderly and a huge personal and societal impact.
      Recent epidemiological studies have indicated that the incidence and age of onset
      of sporadic AD can be modified by lifestyle factors such as education, exercise,
      and (early) stress exposure. Early life adversity is known to promote cognitive
      decline at a later age and to accelerate aging, which are both primary risk
      factors for AD. In rodent models, exposure to 'negative' or 'positive' early life
      experiences was recently found to modulate various measures of AD neuropathology,
      such as amyloid-beta levels and cognition at later ages. Although there is
      emerging interest in understanding whether experiences during early postnatal
      life also modulate AD risk in humans, the mechanisms and possible substrates
      underlying these long-lasting effects remain elusive. METHODS: We review
      literature and discuss the role of early life experiences in determining later
      age and AD-related processes from a brain and cognitive 'reserve' perspective. We
      focus on rodent studies and the identification of possible early determinants of
      later AD vulnerability or resilience in relation to early life
      adversity/enrichment. RESULTS: Potential substrates and mediators of early life
      experiences that may influence the development of AD pathology and cognitive
      decline are: programming of the hypothalamic-pituitary-adrenal axis, priming of
      the neuroinflammatory response, dendritic and synaptic complexity and function,
      overall brain plasticity, and proteins such as early growth response protein 1
      (EGR1), activity regulated cytoskeleton-associated protein (Arc), and repressor
      element-1 silencing transcription factor (REST). CONCLUSIONS: We conclude from
      these rodent studies that the early postnatal period is an important and
      sensitive phase that influences the vulnerability to develop AD pathology. Yet
      translational studies are required to investigate whether early life experiences
      also modify AD development in human studies, and whether similar molecular
      mediators can be identified in the sensitivity to develop AD in humans.

PMID- 30227891
TI  - Findings of DTI-p maps in comparison with T2/T2-FLAIR to assess postoperative
      hyper-signal abnormal regions in patients with glioblastoma.
AB  - PURPOSE: The aim of this study was to compare diffusion tensor imaging (DTI)
      isotropic map (p-map) with current radiographically (T2/T2-FLAIR) methods based
      on abnormal hyper-signal size and location of glioblastoma tumor using a semi
      automatic approach. MATERIALS AND METHODS: Twenty-five patients with biopsy
      proved diagnosis of glioblastoma participated in this study. T2, T2-FLAIR images
      and diffusion tensor imaging (DTI) were acquired 1 week before radiotherapy.
      Hyper-signal regions on T2, T2-FLAIR and DTI p-map were segmented by means of
      semi-automated segmentation. Manual segmentation was used as ground truth. Dice
      Scores (DS) were calculated for validation of semiautomatic method. Discordance
      Index (DI) and area difference percentage between the three above regions from
      the three modalities were calculated for each patient. RESULTS: Area of
      abnormality in the p-map was smaller than the corresponding areas in the T2 and
      T2-FLAIR images in 17 patients; with mean difference percentage of 30 +/- 0.15
      and 35 +/- 0.15, respectively. Abnormal region in the p-map was larger than the
      corresponding areas in the T2-FLAIR and T2 images in 4 patients; with mean
      difference percentage of 26 +/- 0.17 and 29 +/- 0.28, respectively. This region
      in the p-map was larger than the one in the T2 image and smaller than the one in
      the T2-FLAIR image in 3 patients; with mean difference percentage of 34 +/- 0.08
      and 27 +/- 0.06, respectively. Lack of concordance was observed ranged from 0.214
      0.772 for T2-FLAIR/p-map (average: 0.462 +/- 0.18), 0.266-0.794 for T2 /p-map
      (average: 0.468 +/- 0.13) and 0.123-0.776 for T2/ T2-FLAIR (average: 0.423 +/-
      0.2). These regions on three modalities were segmented using a semi-automatic
      segmentation method with over 86% sensitivity, 90% specificity and 89% dice score
      for three modalities. CONCLUSION: It is noted that T2, T2-FLAIR and DTI p-maps
      represent different but complementary information for delineation of glioblastoma
      tumor margins. Therefore, this study suggests DTI p-map modality as a candidate
      to improve target volume delineation based on conventional modalities, which
      needs further investigations with follow-up data to be confirmed.

PMID- 30227892
TI  - Predicting recurrence of Clostridium difficile infection following encapsulated
      fecal microbiota transplantation.
AB  - BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for
      recurrent Clostridium difficile infection (rCDI). The use of freeze-dried,
      encapsulated donor material for FMT (cap-FMT) allows for an easy route of
      administration and remains clinically effective in the majority of rCDI patients.
      We hypothesized that specific shifts in the microbiota in response to cap-FMT
      could predict clinical outcome. We further evaluated the degree of donor
      microbiota engraftment to determine the extent that donor transfer contributed to
      recovery. RESULTS: In total, 89 patients were treated with 100 separate cap-FMTs,
      with a success rate (no rCDI 60 days post cap-FMT) of 80%. Among responders, the
      lower alpha diversity (ANOVA P < 0.05) observed among patient's pre-FMT samples
      was restored following cap-FMT. At 1 week post-FMT, community composition varied
      by clinical outcome (ANOSIM P < 0.001), with similar abundances among families
      (Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae) in responder and donor
      samples. Families that showed differential abundances by outcome (response vs.
      recurrence) from samples collected 7 days following cap-FMT were used to
      construct a regression tree-based model to predict recurrence. Results showed a
      training accuracy of 100% to predict recurrence and the model was 97% accurate
      against a test data set of samples collected 8-20 days following cap-FMT.
      Evaluation of the extent of engraftment using the Bayesian algorithm
      SourceTracker revealed that approximately 50% of the post-FMT communities of
      responders were attributable to donor microbiota, while an additional 20-30% of
      the communities were similar to a composite healthy microbiota consisting of all
      donor samples. CONCLUSIONS: Regression tree-based analyses of microbial
      communities identified taxa significantly related to clinical response after 7
      days, which can be targeted to improve microbial therapeutics. Furthermore,
      reinstatement of a healthy assemblage following cap-FMT was only partially
      attributable to explicit donor engraftment and continued to develop towards an
      overall healthy assemblage, independent of donor.

PMID- 30227893
TI  - Quick efficacy seeking trial (QuEST1): a novel combination immunotherapy study
      designed for rapid clinical signal assessment metastatic castration-resistant
      prostate cancer.
AB  - : Advances in immunotherapy utilizing immune checkpoint inhibitors (ICIs) have
      transformed the treatment landscapes of several malignancies in recent years.
      Oncologists are now tasked with extending these benefits to a greater number of
      patients and tumor types. Metastatic castration-resistant prostate cancer (mCRPC)
      infrequently responds to ICIs, while the cellular vaccine approved for mCRPC,
      sipuleucel-T, provides a 4-month survival benefit but does not produce clinical
      responses as monotherapy. However, many novel and generally well-tolerated immune
      oncology agents with potential for immune synergy and/or additive effects are
      undergoing clinical development. This availability presents opportunities to
      develop adaptive-design combination clinical trials aimed to generate, expand,
      and facilitate antitumor immune responses. Here we describe a currently accruing
      phase I/II trial (NCT03493945) testing a brachyury-targeted antitumor vaccine,
      TGF-beta TRAP/anti-PD-L1 antibody, an IL-15 agonist, and an IDO1 inhibitor in
      mCRPC. TRIAL REGISTRATION: This trial ( NCT03493945 ) was registered in National
      Clinical Trials on April 11th 2018.

PMID- 30227894
TI  - Significant bleeding from Meckel's diverticulum after blunt abdominal trauma: a
      case report.
AB  - BACKGROUND: Meckel's diverticulum, with an incidence of 2%, is the most common
      congenital anomaly in the gastrointestinal tract. Its main complications are
      perforation, obstruction, and bleeding. A few studies have reported that blunt
      abdominal trauma may result in perforation or obstruction to Meckel's
      diverticulum. However, reports of significant major intestinal bleeding from
      Meckel's diverticulum as a complication of blunt abdominal trauma is rare. This
      paper present what we believe to be the first reported case of significant
      intestinal bleeding from a Meckel's diverticulum following blunt abdominal
      trauma. CASE PRESENTATION: A 12-year-old Saudi boy of Arab ethnicity presented to
      the King Saud Medical City emergency department with bleeding per rectum and mild
      abdominal pain following blunt trauma to his abdomen. On examination, his abdomen
      was slightly tender, bowel sounds were present, and he was hemodynamically
      stable. During admission, rectal bleeding was ongoing. On day 3 he deteriorated
      with decreasing blood pressure and hemoglobin, and increasing pulse rate with
      fever. After resuscitation and stabilization, he was urgently taken to the
      operating room for further diagnostic management and treatment. His nasogastric
      tube revealed bile without blood, and an intraoperative colonoscopy revealed
      altered blood within his whole colon and terminal ileum without a definite
      bleeding site. A laparotomy was performed, and an injured branch of the
      mesenteric artery supplying the Meckel's diverticulum was identified as the
      source of the significant arterial bleeding. Suture ligation controlled the
      bleeding, and the Meckel's diverticulum was resected. The patient remained stable
      after that until discharge without any further intestinal bleeding. CONCLUSION:
      Identifying bleeding as a complicated Meckel's diverticulum following blunt
      trauma to the abdomen can be challenging due to its low incidence and
      difficulties while making the diagnosis.

PMID- 30227895
TI  - The impact of transcranial magnetic stimulation on diagnostic confidence in
      patients with Alzheimer disease.
AB  - BACKGROUND: Cholinergic dysfunction is a key abnormality in Alzheimer disease
      (AD) that can be detected in vivo with transcranial magnetic stimulation (TMS)
      protocols. Although TMS has clearly demonstrated analytical validity, its
      clinical utility is still debated. In the present study, we evaluated the
      incremental diagnostic value, expressed in terms of diagnostic confidence of
      Alzheimer disease (DCAD; range 0-100), of TMS measures in addition to the routine
      clinical diagnostic assessment in patients evaluated for cognitive impairment as
      compared with validated biomarkers of amyloidosis. METHODS: One hundred twenty
      patients with dementia were included and scored in terms of DCAD in a three-step
      assessment based on (1) demographic, clinical, and neuropsychological evaluations
      (clinical work-up); (2) clinical work-up plus amyloid markers (cerebrospinal
      fluid or amyloid positron emission tomographic imaging); and (3) clinical work-up
      plus TMS intracortical connectivity measures. Two blinded neurologists were asked
      to review the diagnosis and diagnostic confidence at each step. RESULTS: TMS
      measures increased the discrimination of DCAD in two clusters (AD-like vs FTD
      like) when added to the clinical and neuropsychological evaluations with levels
      comparable to established biomarkers of brain amyloidosis (cluster distance of
      55.1 for clinical work-up alone, 76.0 for clinical work-up plus amyloid markers,
      80.0 for clinical work-up plus TMS). Classification accuracy for the "gold
      standard" diagnosis (dichotomous - AD vs FTD - variable) evaluated in the three
      step assessment, expressed as AUC, increased from 0.82 (clinical work-up alone)
      to 0.98 (clinical work-up plus TMS) and to 0.99 (clinical work-up plus
      amyloidosis markers). CONCLUSIONS: TMS in addition to routine assessment in
      patients with dementia has a significant effect on diagnosis and diagnostic
      confidence that is comparable to well-established amyloidosis biomarkers.

PMID- 30227896
TI  - A systematic review and network meta-analysis comparing azacitidine and
      decitabine for the treatment of myelodysplastic syndrome.
AB  - BACKGROUND: Hypomethylating agents (HMA), azacitidine, and decitabine are
      frequently used in the management of myelodysplastic syndromes (MDS). However,
      there are no clinical trials that have directly compared these agents. We
      conducted a systematic review and indirectly compared the efficacy of azacitidine
      to decitabine in MDS. METHODS: We conducted a comprehensive search of several
      databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and
      Scopus) through June 28, 2018, without language or time restrictions. Studies
      were screened by two independent reviewers, and differences were resolved by
      consensus. The fixed effect model and adjusted indirect comparison methods were
      used to pool relative risks (RR) of major outcomes of interest (mortality,
      response rate, quality of life, hematologic improvement, hospitalization,
      leukemia transformation, transfusion independence). RESULTS: Only four trials met
      the eligibility criteria. Two trials compared azacitidine to the best supportive
      care (BSC) and included 549 patients, and the other two compared decitabine to
      BSC and included 403 patients. The risk of bias was unclear overall. Compared to
      BSC, azacitidine was significantly associated with lower mortality (RR = 0.83,
      95% CI 0.74-0.94, I2 = 89%) whereas decitabine did not significantly reduce
      mortality (RR = 0.88, 95% CI 0.77-1.00, I2 = 53%). Both drugs were associated
      with higher partial and complete response compared to BSC. Indirect comparisons
      were not statistically significant for all the studied outcomes, except for
      complete response where azacitidine was less likely to induce complete response
      compared to decitabine (RR = 0.11, 95% CI = 0.01-0.86, very low-certainty
      evidence). CONCLUSIONS: Azacitidine and decitabine are both associated with
      improved outcomes compared to BSC. The available indirect evidence comparing the
      two agents warrants very low certainty and cannot reliably confirm the
      superiority of either agent. Head-to-head trials are needed. In the meantime, the
      choice of agent should be driven by patient preferences, adverse effects, drug
      availability, and cost.

PMID- 30227898
TI  - Antimicrobial stewardship for acute-care hospitals: An Asian perspective.
AB  - Inappropriate use of antibiotics is contributing to a serious antimicrobial
      resistance problem in Asian hospitals. Despite resource constraints in the
      region, all Asian hospitals should implement antimicrobial stewardship (AMS)
      programs to optimize antibiotic treatment, improve patient outcomes, and minimize
      antimicrobial resistance. This document describes a consensus statement from a
      panel of regional experts to help multidisciplinary AMS teams design programs
      that suit the needs and resources of their hospitals. In general, AMS teams must
      decide on appropriate interventions (eg, prospective audit and/or formulary
      restriction) for their hospital, focusing on the most misused antibiotics and
      problematic multidrug-resistant organisms. This focus is likely to include
      carbapenem use with the goal to reduce carbapenem-resistant gram-negative
      bacteria. Rather than initially trying to introduce a comprehensive, hospital
      wide AMS program, it would be practical to begin by pilot testing a simple
      program based on 1 achievable core intervention for the hospital. AMS team
      members must work together to determine the most suitable AMS interventions to
      implement in their hospitals and how best to put them into practice. Continuous
      monitoring and feedback of outcomes to the AMS teams, hospital administration,
      and prescribers will enhance sustainability of the AMS programs.

PMID- 30227897
TI  - Dynamics of microbial populations mediating biogeochemical cycling in a
      freshwater lake.
AB  - BACKGROUND: Microbial processes are intricately linked to the depletion of oxygen
      in in-land and coastal water bodies, with devastating economic and ecological
      consequences. Microorganisms deplete oxygen during biomass decomposition,
      degrading the habitat of many economically important aquatic animals. Microbes
      then turn to alternative electron acceptors, which alter nutrient cycling and
      generate potent greenhouse gases. As oxygen depletion is expected to worsen with
      altered land use and climate change, understanding how chemical and microbial
      dynamics impact dead zones will aid modeling efforts to guide remediation
      strategies. More work is needed to understand the complex interplay between
      microbial genes, populations, and biogeochemistry during oxygen depletion.
      RESULTS: Here, we used 16S rRNA gene surveys, shotgun metagenomic sequencing, and
      a previously developed biogeochemical model to identify genes and microbial
      populations implicated in major biogeochemical transformations in a model lake
      ecosystem. Shotgun metagenomic sequencing was done for one time point in Aug.,
      2013, and 16S rRNA gene sequencing was done for a 5-month time series (Mar.-Aug.,
      2013) to capture the spatiotemporal dynamics of genes and microorganisms
      mediating the modeled processes. Metagenomic binning analysis resulted in many
      metagenome-assembled genomes (MAGs) that are implicated in the modeled processes
      through gene content similarity to cultured organism and the presence of key
      genes involved in these pathways. The MAGs suggested some populations are capable
      of methane and sulfide oxidation coupled to nitrate reduction. Using the model,
      we observe that modulating these processes has a substantial impact on overall
      lake biogeochemistry. Additionally, 16S rRNA gene sequences from the metagenomic
      and amplicon libraries were linked to processes through the MAGs. We compared the
      dynamics of microbial populations in the water column to the model predictions.
      Many microbial populations involved in primary carbon oxidation had dynamics
      similar to the model, while those associated with secondary oxidation processes
      deviated substantially. CONCLUSIONS: This work demonstrates that the unique
      capabilities of resident microbial populations will substantially impact the
      concentration and speciation of chemicals in the water column, unless other
      microbial processes adjust to compensate for these differences. It further
      highlights the importance of the biological aspects of biogeochemical processes,
      such as fluctuations in microbial population dynamics. Integrating gene and
      population dynamics into biogeochemical models has the potential to improve
      predictions of the community response under altered scenarios to guide
      remediation efforts.

PMID- 30227899
TI  - Alcoholic family marital heterogeneity aggregates different child behavior
      problems both pre- and postseparation.
AB  - Children of alcoholics (COAs) are at risk for elevated internalizing and
      externalizing symptoms. Yet, little is known about the familial and behavioral
      adjustments of COAs following parental separation. Using an ecological
      transactional framework, we examined how multiple risk factors contributed to the
      formation of different alcoholic family structures and how living in
      heterogeneous family structures affected COAs' behavioral problems. The Michigan
      Longitudinal Study, a multiwave study on initially intact alcoholic and control
      families with preschool-age children (n = 503), was used to evaluate outcomes of
      offspring, when families either remained intact or were separated when the child
      was aged 12-14. Alcoholic families who later transitioned into stepfamilies were
      characterized with higher paternal antisociality, marital aggression, and serious
      family crises than alcoholic families that remained intact. COAs in stepfamilies
      (but not in single-parent families) exhibited higher levels of internalizing and
      externalizing symptoms in preadolescence compared with those in alcoholic intact
      families, in part because of elevated behavioral risk at age 3. Structural
      equation modeling indicated that the aggregated risk of stepfamily residence
      directly related to COAs' internalizing and indirectly related to COAs'
      externalizing problems, partially mediated by family stressors. Findings suggest
      targeting COAs in separated families for early intervention.

PMID- 30227900
TI  - Liquid Chromatography Method for the Simultaneous Quantification of Biotin and
      Vitamin B12 in Vitamin B Supplements.
AB  - Background: The determination of cyanocobalamin (vitamin B12) and biotin has
      always been challenging because of the lack of a chromophore for biotin and trace
      level input for vitamin B12 in supplements. Microbiological assay methods are
      currently used for quantitation. However, these methods are time consuming, may
      lack specificity, and have high imprecision. Objective: Our laboratory developed
      and validated an LC method for the simultaneous quantitation of vitamin B12 and
      biotin. Methods: This LC method uses a single quadruple mass analyzer to detect
      biotin and vitamin B12 at m/z 245.10 and m/z 678.29, respectively. Results: The
      mass analyzer allows for low limits of quantitation (biotin: 1 ng/mL; vitamin
      B12: 4 ng/mL). Precision results showed that injections are repeatable without
      the use of an internal standard (RSD < 5%). Single analyst (n = 5: RSD < 3%),
      within lab (n = 10: RSD < 8%), and multilab (n = 20: RSD < 13%) precision results
      were also much better than those reported by microbiological assay methods.
      Linearity was evaluated between 92.00 ng/mL and 9200 ng/mL (R2 09916) for biotin
      and between 4.846 ng/mL and 484.6 ng/mL (R2 0.9999) for vitamin B12. The method
      is accurate between 20 ng/mL and 60 ng/mL for vitamin B12 and between 400 ng/mL
      and 1200 ng/mL for biotin. Conclusions: The results show a simple, accurate, and
      precise method for the quantitation of vitamin B12 and biotin. Highlights: This
      work demonstrates that single quadrupole mass analyzers can be successfully used
      to quantify trace level analytes in quality control laboratories.

PMID- 30227901
TI  - Quantitative Detection of Beef Contamination in Cooked Meat Products by ELISA.
AB  - Background: Concerns about the contamination of meat products with undeclared
      meats, and new regulations for the declaration of meat adulterants have
      established the need for a rapid test to detect beef adulteration to 0.1%
      sensitivity. Objective: To address this need, Microbiologique, Inc. has developed
      an ELISA that can quantify the presence of beef down to 0.1% (w/w) in cooked
      pork, horse, chicken, goat, and sheep meat. Results: The beef-authentication
      ELISA has an analytical sensitivity of 0.00022 and 0.00012% (w/v) for cooked and
      autoclaved beef, respectively, and an analytical range of quantitation of 0.025
      to 2% (w/v), in the absence of other meats. Moreover, the assay is specific for
      cooked beef and does not cross react with common food matrixes. Conclusions: The
      assay is rapid, can be completed in 70 min, and can detect a 0.1% level of meat
      adulteration. The assay is an improvement over a previous U.S. Department of
      Agriculture's tested assay, which is sensitive to 1% adulteration and takes 2.5-3
      h to complete. Highlights: The Microbiologique Cooked Beef ELISA can quantitate
      cooked beef in the presence of pork, horse, chicken, goat, and sheep meat to 0.1%
      (w/w) and is not affected by common food matrixes.

PMID- 30227903
TI  - Determination of Total Flavonoids for Paris Polyphylla Var. Yunnanensis in
      Different Geographical Origins Using UV and FT-IR Spectroscopy.
AB  - Background: Paris polyphylla var. yunnanensis (PPY) is used in the clinical
      treatment of tumors, hemorrhages, and anthelmintic. Objective: The aim of this
      study is to determine total flavonoids of PPY in the Yunnan and Guizhou
      Provinces, China. Methods: In this study, total flavonoids were determined by UV
      spectrophotometry at first. Then, Fourier transform mid-infrared (FT-IR) based on
      various pretreatments include standard normal variate (SNV), first derivative
      (FD), second derivative (SD), Savitzky-Golay (SG), and orthogonal signal
      correction (OSC) were investigated. In addition, several relevant variables were
      screened by competitive adaptive reweighted sampling (CARS). The content of total
      flavonoids and selected variables of FT-IR were used to establish a partial least
      squares regression for PPY in different regions. Results: The results indicated
      that CARS was an effective method for decreasing the variable of the database and
      improving the prediction of the model. FT-IR with pretreatment SNV + OSC + FD +
      SG had the best performance, with R2 > 0.9 and residual predictive deviation =
      3.3515, which could be used for the predictive model of total flavonoids.
      Conclusions: Those results would provide a fast and robust strategy for the
      determination of total flavonoids of PPY in different geographical origin.
      Highlights: Various pretreatments, including SNV, FD, SD, SG, and OSC, were
      compared; several relevant variables were selected by CARS; and the content of
      total flavonoids and selected variable were used to establish a partial least
      squares regression for PPY in different regions.

PMID- 30227902
TI  - Allograft Inflammatory Factor 1 as an Immunohistochemical Marker for Macrophages
      in Multiple Tissues and Laboratory Animal Species.
AB  - Allograft inflammatory factor 1 (AIF1) is a commonly used marker for microglia in
      the brains of humans and some animal models but has had limited applications
      elsewhere. We sought to determine whether AIF1 can be used as a macrophage marker
      across common laboratory animal species and tissues. We studied tissues (that is,
      spleen, liver, and lung) with defined macrophage populations by using an AIF1
      immunostaining technique previously validated in human tissue. Tissues were
      collected from various mouse strains (n = 20), rat strains (n = 15), pigs (n =
      4), ferrets (n = 4), and humans (n = 4, lung only). All samples of liver had
      scattered immunostaining in interstitial cells, consistent with resident tissue
      macrophages (Kupffer cells). Spleen samples had cellular immunostaining of
      macrophages in both the red and white pulp compartments, but the red pulp had
      more immunostained cellular aggregates and, in some species, increased
      immunostaining intensity compared with white pulp. In lung, alveolar macrophages
      had weak to moderate staining, whereas interstitial and perivascular macrophages
      demonstrated moderate to robust staining. Incidental lesions and tissue changes
      were detected in some sections, including a tumor, inducible bronchus-associated
      lymphoid tissue, and inflammatory lesions that demonstrated AIF1 immunostaining
      of macrophages. Finally, we compared AIF1 immunostaining of alveolar macrophages
      between a hypertensive rat model (SHR strain) and a normotensive model (WKY
      strain). SHR lungs had altered intensity and distribution of immunostaining in
      activated macrophages compared with macrophages of WKY lungs. Overall, AIF1
      immunostaining demonstrated reproducible macrophage staining across multiple
      species and tissue types. Given the increasing breadth of model species used to
      study human disease, the use of cross-species markers and techniques can reduce
      some of the inherent variability within translational research.

PMID- 30227904
TI  - Determination of Ethanol Content in Kombucha Products by Gas Chromatography with
      Flame Ionization Detection: A Multilaboratory Study.
AB  - Background: Kombucha is a nonalcoholic, fermented tea beverage that has recently
      received negative attention because of documented concentrations of ethanol in
      excess of allowable limits of >=0.05% alcohol by volume (ABV). Objective: Our
      previously reported headspace GC with flame-ionization detection (GC-FID) method
      was adopted by the AOAC Expert Review Panel as First Action Official MethodSM
      2016.12 in September 2016 based on published single-laboratory validation study
      results. This paper describes the corresponding multilaboratory study using this
      method to further validate its performance parameters. Methods: Four laboratories
      participated in the study and received practice samples, test samples, reference
      standards, and detailed protocols. Eight kombucha samples sent out to
      laboratories were randomly assigned sample numbers and were blinded in terms of
      content and identity. Each laboratory analyzed all samples using the GC-FID
      method and reported their results. Results: Cochran's C-test and single and
      double Grubbs' tests were used to identify and remove outliers. Horwitz ratio
      values for all samples were between 0.5 and 1.7. As per the Standard Method
      Performance Requirements (SMPRs(r)), all samples within the analytical range of
      0.1-2.0 ABV% had RSDR values <6%. Conclusions: The results from this study
      demonstrate the evaluated GC-FID method meets the SMPR requirements and is fit
      for purpose for detecting ethanol in kombucha products. Highlights: Kombucha, a
      nonalcoholic, fermented beverage, has been found to contain >=0.05% ABV. First
      Action Official Method 2016.12, a headspace GC-FID method for determining ethanol
      in kombucha, is supported by a multilaboratory study.

PMID- 30227905
TI  - Improvement in the Reliability of AOAC Official Method 2012.15 for Iodine.
AB  - Background: Reliable measurements of iodine are essential for ensuring the
      quality of infant formula. The AOAC Official Method 2012.15 for iodine tends to
      produce higher results in the presence of carbon remaining in the final test
      solution after digestion with alkaline dissolution. This is partly because of the
      lack of countermeasures for signal enhancement induced by coexisting carbon in
      Method 2012.15. Objective: To obtain more reliable values for infant formulas, we
      undertook an experiment. Methods: We modified the protocol by adding carbon in
      the form of methanol to both the standard solutions and the final test solutions.
      Comparisons of the enhancement factor for iodine-127 were used to find the
      optimized concentration of methanol from 0-10%. Results: Optimization of the
      additional carbon showed that a 5% methanol minimum was necessary for a constant
      ratio of iodine. The results exhibited good linearity (coefficient of
      determination >0.999), and the LOQ was 0.19 MUg/kg for the reconstituted final
      product with a methanol concentration of 5%. The intermediate precision RSD was
      <3.76%, and the recovery factor was 97.5-104.2% for infant formula distributed in
      several countries and a special formula distributed in Japan. Conclusions: This
      demonstrates that 5% methanol, when added to standard and final solutions, acts
      as an effective matrix matching agent. Highlights: This modified method produces
      more accurate iodine quantification in infant formulas and special formulas in
      which there is incomplete digestion of the matrix.

PMID- 30227906
TI  - Management of Hypertension on the Labor and Delivery Unit: Delivering Care in the
      Era of Protocols and Algorithms.
AB  - INTRODUCTION: Preeclampsia with severe hypertension, which occurs in 5% to 8% of
      pregnancies, is a leading cause of maternal and perinatal morbidity and mortality
      in the US. Early recognition and treatment of hypertensive crises can
      significantly reduce poor outcomes. A protocol to ensure prompt treatment with
      antihypertensive medication (intravenous labetalol) was implemented at our
      institution. OBJECTIVE: To determine adherence to this protocol on the Labor and
      Delivery Unit. DESIGN: Retrospective chart review was performed for patients
      admitted to the Labor and Delivery Unit between April 2015 and June 2015. Charts
      were reviewed if the patient had a diagnosis of chronic hypertension, gestational
      hypertension, superimposed preeclampsia, preeclampsia with severe features,
      eclampsia, or stroke in pregnancy. Only patients with confirmed severe blood
      pressures, in which the protocol would be initiated, were included in the final
      analysis. MAIN OUTCOME MEASURE: Overall compliance with the entire protocol.
      RESULTS: Of 178 cases reviewed, 58 (32.6%) had confirmed severe blood pressures.
      Most patients (n = 46, 79.3%) received a diagnosis of preeclampsia with severe
      features, and most delivered via cesarean delivery (n = 38, 65.5%). No cases were
      compliant with the entire labetalol protocol. Of 58 patients, 2 (3.5) adequately
      repeated a confirmation blood pressure within 5 minutes, and 34 (58.6%) were
      adequately treated with intravenous labetalol according to protocol requirements.
      CONCLUSION: Labetalol treatment was appropriately initiated in many cases;
      however, protocol adherence could greatly improve. Potential factors affecting
      protocol compliance include shift changes, communication issues, and conflicting
      protocols. Institutions should review protocol compliance to improve care.

PMID- 30227907
TI  - Developing Community-Based Primary Health Care for Complex and Vulnerable
      Populations in the Vancouver Coastal Health Region: HealthConnection Clinic.
AB  - INTRODUCTION: Designing, delivering, and evaluating high-performing primary
      health care services for complex and vulnerable subpopulations are challenging
      endeavors. However, there is a relative paucity of research evidence available to
      support such work. OBJECTIVE: To provide a case study using HealthConnection
      Clinic, a public primary care center located in Metropolitan Vancouver's North
      Shore. METHODS: Developmental evaluation approach operationalizing the 10
      Building Blocks of High-Performing Primary Care framework using qualitative and
      quantitative methods. RESULTS: The clinic provided valuable insights to
      policymakers and researchers related to development of the Building Blocks'
      foundational elements, particularly engaged leadership, empanelment, and data
      driven improvement. The study highlighted the key enablers, achievements,
      challenges, and barriers related to operationalizing each Building Block. The
      Building Blocks were a useful heuristic that enabled the development and
      evaluation of primary care for complex subpopulations. Particularly salient from
      a Canadian policy perspective was the demonstration that system integration was
      possible when highly engaged leaders from a Regional Health Authority and a
      Division of Family Practice shared a common vision and purpose. HealthConnection
      Clinic's entrepreneurial spirit has enabled the development of innovative,
      evidence-based tools such as the AMPS complexity assessment tool (attachment,
      medical conditions, psychological/mental health/addictions challenges, and
      socioeconomic status), designed to identify and assess biopsychosocial complexity
      and needs. The study also highlighted the importance of incorporating community
      orientation and equity into developmental work. CONCLUSION: The study
      demonstrates how the Building Blocks approach can be adapted to operationalize
      high-performing primary care standards in settings serving complex and vulnerable
      populations.

PMID- 30227908
TI  - Image Diagnosis: Dysphagia Lusoria-An Unusual Cause of Dysphagia Diagnosed with
      Endoscopic Ultrasound.

PMID- 30227909
TI  - Spotlight on Antidiabetic Agents with Cardiovascular or Renoprotective Benefits.
AB  - Type 2 diabetes mellitus often goes hand in hand with cardiovascular and renal
      comorbidities. Stroke, myocardial infarction, heart failure, and chronic kidney
      disease are high-risk complications of type 2 diabetes that contribute to
      morbidity and mortality. Recent clinical trials have uncovered evidence that
      certain antidiabetic agents may confer cardiovascular and/or renal benefits such
      as reduced cardiovascular and all-cause mortality and reduced need for renal
      replacement therapy. Two landmark trials in particular, EMPA-REG OUTCOME
      (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) and
      LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular
      Outcome Results), demonstrated the cardioprotective and/or renoprotective effects
      of empagliflozin and liraglutide, respectively. These trials led to new US Food
      and Drug Administration indications for empagliflozin and liraglutide as risk
      reduction for major cardiovascular events in adults with type 2 diabetes and
      established cardiovascular disease. Other trials are under way to determine
      whether these benefits are class effects and what other agents may have a role in
      risk reduction for cardiovascular and renal disease. This review will summarize
      the evidence for noninsulin antidiabetic drugs with benefits beyond glycemic
      control, discuss proposed mechanisms for these effects, and consider their place
      in therapy.

PMID- 30227911
TI  - My Siren.

PMID- 30227910
TI  - Contraception after Abortion and Risk of Repeated Unintended Pregnancy among
      Health Plan Members.
AB  - CONTEXT: Optimizing access to effective contraception at the time of abortion can
      reduce repeated unintended pregnancies. OBJECTIVE: To assess contraception
      initiation and repeated unintended pregnancies among women receiving abortions in
      Kaiser Permanente Northern California (KPNC) facilities and through outside
      contracted facilities. DESIGN: A retrospective cohort study was conducted using a
      randomized proportional sample of women aged 15 to 44 years having abortions in
      KPNC, to determine contraception initiation within 90 days. Demographic and
      clinical characteristics (age, race/ethnicity, gravidity, parity, contraceptive
      method initiated, and pregnancies within 12 months) were collected from
      electronic health records. Descriptive statistics, chi2 tests, t-tests, and
      logistic regression models assessed predictors of long-acting reversible
      contraception (LARC) initiation and having another unintended pregnancy within 12
      months of abortion. RESULTS: Women having abortions from contracted facilities
      were significantly less likely to initiate LARC within 90 days compared with
      those receiving abortions in KPNC facilities (11.99% vs 19.10%, p = 0.012).
      Significant factors associated with 90-day LARC initiation included abortions in
      KPNC facilities (adjusted odds ratio [aOR] = 1.87, p = 0.007) and gravidity of 3
      or more. Women initiating short-acting or no contraception were significantly
      more likely to have an unintended pregnancy within 12 months of the abortion than
      those initiating LARC (aOR = 3.66, p = 0.005; no contraception vs LARC, aOR =
      3.75, p = 0.005). CONCLUSION: In response to this study, KPNC now provides
      reimbursement for LARC in all outside abortion contracts, internalized more
      abortions in KPNC facilities, and strengthened clinical recommendations for
      immediate, effective postabortion contraception, especially LARC.

PMID- 30227913
TI  - To Pace or Not To Pace? A Narrative Review of VIP Syndrome.

PMID- 30227912
TI  - Uses and Misuses of Patient- and Neighborhood-level Social Determinants of Health
      Data.
AB  - Health care leaders in the US are actively exploring strategies to identify and
      address patients' social and economic hardships as part of high-quality clinical
      care. The result has been a proliferation of screening tools and interventions
      related to patients' social determinants of health, but little guidance on
      effective strategies to implement them. Some of these tools rely on patient- or
      household-level screening data collected from patients during medical encounters.
      Other tools rely on data available at the neighborhood-level that can be used to
      characterize the environment in which patients live or to approximate patients'
      social or economic risks. Four case examples were selected from different health
      care organizations to illustrate strengths and limitations of using patient- or
      neighborhood-level social and economic needs data to inform a range of
      interventions. This work can guide health care investments in this rapidly
      evolving arena.

PMID- 30227914
TI  - Symptom assessment to guide treatment selection and determine progression in
      metastatic castration-resistant prostate cancer: Expert opinion and review of the
      evidence.
AB  - Multiple new agents to treat metastatic castration-resistant prostate cancer
      (mCRPC) have become available in recent years; however, the appropriate timing
      and sequencing of these agents have yet to be elucidated. Until accurate
      biomarkers become available to allow more focused therapeutic targeting for this
      population, treatment selection for men with mCRPC will continue to be driven
      largely by close assessment of patient-related factors and symptoms. Pain, as the
      predominant symptom of mCRPC, is often the focus when assessing progression and
      the need for a change in treatment. A myriad of other symptoms, including
      fatigue, impact on activities of daily living, sleep, and lower urinary tract
      symptoms, also affect men with mCRPC, and assessment of the composite of these
      symptoms provides an earlier signal for the need to adjust treatment. A number of
      tools are available for assessing symptoms in patients with advanced prostate
      cancer, but they are not routinely used, given their complexity and length. A new
      simplified questionnaire is proposed for the assessment of symptoms, beyond pain,
      to inform treatment decisions for men with mCRPC.

PMID- 30227915
TI  - Ruling out esophageal varices in NAFLD cirrhosis: Can we do without endoscopy?

PMID- 30227916
TI  - Assessing the cost-effectiveness of hepatitis C screening strategies in France.
AB  - BACKGROUND & AIMS: In Europe, hepatitis C virus (HCV) screening still targets
      people at high risk of infection. We aim to determine the cost-effectiveness of
      expanded HCV screening in France. METHODS: A Markov model simulated chronic
      hepatitis C (CHC) prevalence, incidence of events, quality-adjusted life years
      (QALYs), costs and incremental cost-effectiveness ratio (ICER) in the French
      general population, aged 18 to 80 years, undiagnosed for CHC for different
      strategies: S1 = current strategy targeting the at risk population; S2 = S1 and
      all men between 18 and 59 years; S3 = S1 and all individuals between 40 and 59
      years; S4 = S1 and all individuals between 40 and 80 years; S5 = all individuals
      between 18 and 80 years (universal screening). Once CHC was diagnosed, treatment
      was initiated either to patients with fibrosis stage >=F2 or regardless of
      fibrosis. Data were extracted from published literature, a national prevalence
      survey, and a previously published mathematical model. ICER were interpreted
      based on one or three times French GDP per capita (?32,800). RESULTS: Universal
      screening led to the lowest prevalence of CHC and incidence of events, regardless
      of treatment initiation. When considering treatment initiation to patients with
      fibrosis >=F2, targeting all people aged 40-80 was the only cost-effective
      strategy at both thresholds (?26,100/QALY). When we considered treatment for all,
      although universal screening of all individuals aged 18-80 is associated with the
      highest costs, it is more effective than targeting all people aged 40-80, and
      cost-effective at both thresholds (?31,100/QALY). CONCLUSIONS: In France,
      universal screening is the most effective screening strategy for HCV. Universal
      screening is cost-effective when treatment is initiated regardless of fibrosis
      stage. From an individual and especially from a societal perspective of HCV
      eradication, this strategy should be implemented. LAY SUMMARY: In the context of
      highly effective and well tolerated therapies for hepatitis C virus that are now
      recommended for all patients, a reassessment of hepatitis C screening strategies
      is needed. An effectiveness and cost-effectiveness study of different strategies
      targeting either the at-risk population, specific ages or all individuals was
      performed. In France, universal screening is the most effective strategy and is
      cost-effective when treatment is initiated regardless of fibrosis stage. From an
      individual and especially from a societal perspective of hepatitis C virus
      eradication, this strategy should be implemented.

PMID- 30227917
TI  - Significant impact of new oral therapies against HCV on the waiting list for
      liver transplantation in Spain.

PMID- 30227918
TI  - Persistence of NS5B-S282T, a sofosbuvir resistance-associated substitution, in a
      HIV/HCV-coinfected MSM with risk of onward transmission.

PMID- 30227919
TI  - NASH-related and cryptogenic cirrhosis similarities extend beyond cirrhosis.

PMID- 30227922
TI  - An Experience of Improvised Laryngoscopy.
AB  - Airway management in the wilderness runs the gamut from basic airway support to
      endotracheal intubation. Fortunately, direct laryngoscopy is a seldom called upon
      skill in expedition medicine. However, the medical skills required during a
      mission or expedition are never truly known in advance. Improvisation during
      evolving medical events is a mainstay of expedition medicine education and
      practice. It is unlikely, given constraints of weight and size of expedition
      medical kits, that a conventional laryngoscope would find its way into a standard
      "go bag." Faced with the real but rare event of needing to intubate a patient in
      an austere environment, how can improvisation be used? Multiple ideas for
      improvised laryngoscopes can be found in the wilderness medicine literature, but
      which, if any, of these devices have true clinical utility? To this end,
      participants of a recent Wilderness Medical Society preconference in medical
      elements of light search and rescue were given the opportunity to devise and
      construct their own improvised laryngoscopes and attempt intubation of a training
      mannequin. Participants with varying degrees of intubating experience improvised
      effective laryngoscopes from provided materials and successfully intubated an
      airway mannequin.

PMID- 30227921
TI  - Self-Reported Use and Attitudes Toward Performance-Enhancing Drugs in
      Ultramarathon Running.
AB  - INTRODUCTION: The use of performance enhancing drugs (PEDs) has been reported in
      several sports. There have been no peer-reviewed articles on the use of PEDs in
      ultramarathon running. This study was to examine the use of PEDs in ultramarathon
      running and to identify attitudes and beliefs about the usage of PEDs in the
      sport. METHODS: An online survey was developed. The survey was distributed to
      potential participants through Ultrasignup and the Western States Endurance Run
      Facebook sites. The survey included 9 demographic questions, 11 PED questions,
      and a previously validated 17-item performance enhancement attitude scale (PEAS).
      RESULTS: Six hundred nine self-identified ultramarathon runners completed the
      survey; 8.4% of respondents reported using PEDs during competition or training.
      Cannabinoids, narcotics, and stimulants were the PEDs that were most frequently
      reported. There was no difference between sex, age, country of origin, rank,
      miles/week of training, or longest race between those that reported using PEDs
      and those that did not report using PEDs. There was, however, a significant
      difference in athletes who reported they knew another ultramarathon runner who
      had used PEDs to have significantly higher years of participation and ranked in
      the top 20th percentile. There additionally was an increased PEAS score of
      individuals who reported using a PED or individuals that knew an individual who
      used PEDs. CONCLUSION: PEDs are being used in ultramarathon running. The exact
      extent of the use of PEDs in ultramarathon running is still unknown and
      challenging to fully investigate without formal, random testing, which is
      expensive and technically challenging.

PMID- 30227923
TI  - Live Surgery: Is Operating at Home the Way Forward?
AB  - Live surgery events are a popular educational tool, but concerns have been
      raised, especially regarding patient safety. The Italian Society of Urology has
      implemented a novel concept in which surgeons operate on their own patients at
      their own institutions, with the procedures broadcast live at the annual society
      meetings. This approach retains the live nature of the surgery but removes the
      risks associated with operating in a foreign environment with distractions.

PMID- 30227924
TI  - Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate
      Cancer: A Prospective Clinical Trial.
AB  - BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging
      treatment option for oligometastatic prostate cancer. However, limited
      prospective evidence is available. OBJECTIVE: To determine the safety and
      feasibility of single fraction SABR for patients with oligometastatic prostate
      cancer. Secondary endpoints were local and distant progression-free survival
      (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen
      response. DESIGN, SETTING, AND PARTICIPANTS: In a prospective clinical trial,
      patients were screened with computed tomography, bone scan, and sodium fluoride
      positron emission tomography scan and had one to three oligometastases. Kaplan
      Meier methods were used to determine LPFS and DPFS. Toxicity was graded using
      Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using
      European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22
      at 1, 3,12, and 24 mo. INTERVENTION: A single fraction of 20-Gy SABR to each
      lesion. RESULTS AND LIMITATIONS: Between 2013 and 2014, 33 consecutive patients
      received SABR to a total of 50 oligometastases and were followed for 2 yr. The
      median age was 70 yr. The Gleason score was >=8 in 15 patients (45%). Twenty
      patients had bone only, 12 had node only, and one had mixed disease. SABR was
      feasible and delivered as planned in 97% of cases. There was one grade 3 adverse
      event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97%
      (95% confidence interval [CI]: 91-100) and 93% (95% CI: 84-100), and DPFS was 58%
      (95% CI: 43-77) and 39% (95% CI: 25-60), respectively. In those not on androgen
      deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no
      significant difference from baseline QoL observed. Limitations include small
      sample size, limited duration of follow-up, and lack of a control arm.
      CONCLUSIONS: A single SABR session was feasible and associated with low morbidity
      in this cohort. Over one-third of patients did not progress and were free from
      ADT at 2-yr. QoL measures were maintained with this treatment strategy. PATIENT
      SUMMARY: This clinical trial investigated single treatment stereotactic
      radiotherapy for low volume advanced prostate cancer. The approach was found to
      be safe with avoidance of hormone therapy in almost half of the participants at 2
      yr.

PMID- 30227925
TI  - It Ain't Over Till the Fat Lady Sings: The POPSTAR Trial.

PMID- 30227927
TI  - Discriminant analysis of volatile organic compounds of Fusarium oxysporum f. sp.
      cepae and Fusarium proliferatum isolates from onions as indicators of fungal
      growth.
AB  - Basal rot is a common onion disease and is mainly caused by Fusarium oxysporum f.
      sp. cepae and Fusarium proliferatum. To study the possibility of using volatile
      organic compounds (VOCs) as biomarkers for these fungi, pathogenic isolates of F.
      oxysporum and F. proliferatum from onions were cultivated in onion medium and
      VOCs were measured by solid phase microextraction (SPME). Forty-two compounds
      were detected, and thirty of these compounds were highly related to fungal
      metabolic activity. Allyl mercaptan was specific to F. oxysporum isolate Fox006.
      Analysis of the VOCs showed significant differences between the two species and
      among different isolates within the same species. Sixteen of the VOCs showed were
      highly positively correlated with the fungal biomass estimated by real-time
      polymerase chain reaction (PCR). Ethanol, ethyl formate, ethyl acetate, 2-methyl
      1-propanol, methyl thioacetate, n-propyl acetate and 3-methyl-1-butanol are
      volatile metabolites that were potential indicators of Fusarium growth on onions.

PMID- 30227926
TI  - Evolution and future of Obstetrics and Gynaecology Nurses specialists (Midwives).

PMID- 30227928
TI  - Generation of Sporothrix schenckii mutants expressing the green fluorescent
      protein suitable for the study of host-fungus interactions.
AB  - Sporotrichosis is an infection caused by members of the Sporothrix genus, and
      among them, Sporothrix schenckii is one of the etiological agents. Both, the
      disease and the causative agent have gained interest in the recent years, because
      of the report of epidemic outbreaks, and the description of the disease
      transmission from animals to human beings. Despite the relevance of S. schenckii
      in the clinical field, there are basic aspects of its biology poorly explored. So
      far, Agrobacterium tumefaciens-mediated transformation has been reported as an
      alternative for genetic manipulation of this fungal pathogen. Here, we report the
      optimization of the transformation method and used this to generate insertional
      mutants that express the green fluorescent protein in S. schenckii. We obtained
      five mutant strains that showed mitotic stability and expression of the reporter
      gene. The strains displayed normal cell wall composition, and a similar ability
      to interact ex vivo with human monocytes and monocyte-derived macrophages.
      Moreover, the virulence in larvae of Galleria mellonella was similar to that
      obtained with the wild-type control strains. These data indicate that these
      fluorescent mutants with normal ability to interact with the host could be used
      in bioimaging to track the host-Sporothrix interaction in vivo.

PMID- 30227929
TI  - Inhibition of virulent and hypovirulent Cryphonectria parasitica growth in dual
      culture by fungi commonly isolated from chestnut blight cankers.
AB  - Chestnut blight cankers, caused by the fungus Cryphonectria parasitica, are prone
      to invasion by other microorganisms as the canker ages. This microbial community
      has the potential to alter canker expansion, which may influence the probability
      that the canker girdles the infected stem. Hypoviruses infect the pathogen
      mycelium directly and are known to decrease pathogen virulence (i.e.
      hypovirulent). These viral infections can slow pathogen growth, decreasing the
      rate of canker expansion and lowering the probability of girdling. Saprophytic
      fungi also invade the expanding canker and may antagonize C. parasitica leading
      to reduced pathogen growth. The combined effects of fungal antagonism and a
      hypovirulent pathogen could work in combination to reduce the probability of
      girdling the infected stem. We assessed the ability of different fungal taxa,
      isolated from low severity cankers, to inhibit the growth of virulent and
      hypovirulent forms of C. parasitica in dual culture tests on two cultural media.
      Percent growth inhibition of virulent C. parasitica by potentially antagonistic
      fungi ranged from 2 % to 34 %, while inhibition of hypovirulent C. parasitica
      ranged from 18 % to 54 %. Only one isolate, identified as Umbelopsis isabellina
      (UmbelopsisWS) inhibited the virulent form of the pathogen more than the
      hypovirulent form. All three Trichoderma isolates caused the greatest growth
      inhibition of virulent C. parasitica, but they, like all other fungal isolates
      tested, inhibited the hypovirulent form of the pathogen more than the virulent
      form. These results suggest that commonly occurring fungi in chestnut blight
      cankers, including Trichoderma, may inhibit the hypovirulent C. parasitica more
      than virulent C. parasitica. Thus, the presence of other fungi in cankers may not
      enhance the effect of hypovirulent C. parasitica to delay cankers from girdling a
      stem but instead intensify canker development.

PMID- 30227930
TI  - Profile of Ophiocordyceps sinensis transcriptome and differentially expressed
      genes in three different mycelia, sclerotium and fruiting body developmental
      stages.
AB  - Ophiocordyceps sinensis, a Chinese complementary and alternative medicine (CAM),
      is an entomopathogenic, fungus, parasitizing larvae of the moth genus Thitarodes.
      It has three stages of the life cycle, i.e., the anamorph mycelia prior to
      infection (Cm_Os), the mycelia sclerotium forming in the caterpillar (Te_Ca), and
      the fruiting bodies or stromata (Te_St). Characterization of the O. sinensis
      transcriptome among these stages could provide a better understanding of the
      underlying biology processes. Transcriptomics of the O. sinensis asexual mycelia
      and hyphae in deceased caterpillars and perithecial stroma was assessed by using
      Illumina HiSeqTM 2000 technology. A total of 14,922 unigenes were identified and
      categorized into 46 sub-categories under three gene ontology categories
      ("biological process", "cellular component", and "molecular function"). Of these
      genes, 5520 were differentially expressed among the libraries of these three
      groups of samples (P < 0.05), and 391 genes occurred in all three groups.
      Compared to the anamorph stage, there were 3049 differentially expressed genes
      (DEGs) in the teleomorph stage, but only 1023 DEGs occurred within the teleomorph
      groups (Te_St vs. Te_Ca). Collectively, this study provides a novel resource to
      further investigate O. sinensis and their three different development stages.

PMID- 30227931
TI  - The role of the veA gene in adjusting developmental balance and environmental
      stress response in Aspergillus cristatus.
AB  - veA belongs to the velvet regulatory system that regulates the development and
      secondary metabolism of many fungi. To identify the function of veA in
      Aspergillus cristatus, veA deletion mutants were constructed by homologous
      recombination via Agrobacterium tumefaciens-mediated transformation. Deletion of
      veA led to increased conidial production and reduced sexual sporulation. The
      regulatory role of veA in A. cristatus was not light-dependent, and this differed
      from its role in other Aspergilli. Furthermore, veA deletion mutants were more
      sensitive to environmental stressors, including salt, osmotic pressure,
      temperature and pH. In contrast, deletion of veA resulted in increased resistance
      to oxidative stress. veA also affected aerial vegetative growth. Transcriptomic
      analysis of the veA-null mutant and wild type indicated that most asexual and
      sexual development genes were upregulated and downregulated, respectively. These
      findings confirmed that veA has a positive effect on sexual development but
      represses conidial formation. Overall, these results suggested that the veA gene
      plays a critical role in maintaining a developmental balance between asexual and
      sexual sporulation and is involved in vegetative growth and environmental stress
      response in A. cristatus.

PMID- 30227932
TI  - Articulospora - Phylogeny vs morphology.
AB  - The taxonomy of the aquatic hyphomycete genus Articulospora (Ascomycota,
      Pezizomycotima, Leotiales, Helotiaceae) is based on the morphology of the
      generative phase of its lifecycle. The type species is Articulospora tetracladia,
      which is distributed worldwide. Its most frequent populations in nature have
      dimorphic conidia, differing by the extent of conidial branching (i.e., one or
      two levels of branching). Some strains, stable in culture, produce exclusively
      conidia of one type. With the molecular analyses employed here and the relatively
      low number of available isolates (20), separation based on branching of conidia
      has not been fully supported. Therefore we propose to retain the broad concept of
      A. tetracladia with dimorphic conidia. Among the three gene sequences tested as
      potential barcodes, the internal transcribed spacer (ITS) gene was the most
      promising region. All strains yielded amplifiable DNA which provided adequate
      resolution, according to accepted ranges in inter/intraspecific differences, to
      differentiate among the three Articulospora and two Fontanospora species that
      were tested (Articulospora atra, Articulospora proliferata, A. tetracladia,
      Fontanospora eccentrica, Fontanospora fusiramosa). D1/D2 primers also permitted
      amplification in all strains, however without much resolution. Amplification of
      the COX1 gene sequence was least consistent.

PMID- 30227933
TI  - Salinity and high pH affect energy pathways and growth in Debaryomyces hansenii.
AB  - The physiological behavior of Debaryomyces hansenii in response to saline stress
      and elevated pH was studied. The combination of 1 M NaCl salt and pH 8.0 was
      required to produce significant changes in the lag phase of growth and a
      consequent effect on viability. pH 8.0 in the absence or presence of 1 M NaCl
      produced changes in physiological functions such as respiration, acidification,
      rubidium transport, transmembrane potential, and fermentation. Our data indicated
      a stimulation of the H+-ATPase of the plasma membrane at pH 8.0, which increased
      the transmembrane potential and favored the entry of Na+; this effect was
      intensified in the presence of NaCl, so the increased energy expenditure
      resulting from H+ pumping and the extrusion of excess Na+ affected viability. The
      gene expression pattern studied by microarrays of cells incubated under saline
      conditions and high pH revealed a down-regulation in genes related to energy
      producing pathways and in some genes involved in the cell cycle and DNA
      transcription, confirming our experimental hypothesis. Although D. hansenii can
      tolerate high pH and high salt concentrations, its physiological behavior, is
      better at pH 6.0 and in the absence of sodium; thus, it is an alkali-halotolerant
      yeast and not a halophilic yeast as previously proposed by other authors.

PMID- 30227934
TI  - Kinetics and pathway of biodegradation of dibutyl phthalate by Pleurotus
      ostreatus.
AB  - Dibutyl phthalate (DBP) is a plasticizer, whose presence in the environment as a
      pollutant has attained a great deal of attention due to its reported association
      with endocrine system disturbances on animals. Growth parameters, glucose uptake,
      percentage of removal efficiency (%E) of DBP, biodegradation constant of DBP (k)
      and half-life of DBP biodegradation (t1/2) were evaluated for Pleurotus ostreatus
      grown on media containing glucose and different concentrations of DBP (0, 500 and
      1000 mg l-1). P. ostreatus degraded 99.6 % and 94 % of 500 and 1000 mg of DBP l-1
      after 312 h and 504 h, respectively. The k was 0.0155 h-1 and 0.0043 h-1 for 500
      and 1000 mg of DBP l-1, respectively. t1/2 was 44.7 h and 161 h for 500 and 1000
      mg of DBP l-1, respectively. Intermediate compounds of biodegraded DBP were
      identified by GC-MS and a DBP biodegradation pathway was proposed using quantum
      chemical calculation. DBP might be metabolized to benzene and acetyl acetate, the
      first would be oxidated to muconic acid and the latter would enter into the Krebs
      cycle. P. ostreatus has the ability to degrade DBP and utilizes it as source of
      carbon and energy.

PMID- 30227935
TI  - Anti-quorum sensing and antibiofilm potential of Alternaria alternata, a foliar
      endophyte of Carica papaya, evidenced by QS assays and in-silico analysis.
AB  - In the present study, secondary metabolites from an endophytic fungus, Alternaria
      alternata, colonizing Carica papaya, demonstrated antiquorum sensing properties
      against Pseudomonas aeruginosa. This study reports the antagonistic effects of
      fungal crude extract of A. alternata against the various quorum sensing (QS)
      associated virulent factors such as percentage decrease in production of
      pyocyanin, alginate, chitinase and rhamnolipid; significant decrease in proteases
      activity such as LasA protease activity, staphylolytic activity, Las B elastase;
      and a marked decrease in biofilm formation and associated factors such as
      exopolysaccharide (EPS) production and cell surface hydrophobicity (CSH).
      Further, motility pattern i.e., swimming and swarming was also found to be
      inhibited. This down regulation of QS and associated factors are further
      supported by in-silico analysis of interaction between QS receptor LasR and
      bioactive molecules viz., sulfurous acid, 2-propyl tridecyl ester and 1,2
      benzenedicarboxylic acid, bis(2-methylpropyl) ester present in fungal crude
      extract, found based on GCMS analysis, sketches the modulating ability of QS
      expression. This is the first report on an endophytic fungus of C. papaya having
      a role in QS inhibition against P. aeruginosa and lays a platform to explore
      further the endophytes for potent therapeutic agents in QS.

PMID- 30227937
TI  - Quantitative evaluation of regional cerebral blood flow changes during childhood
      using 123I-N-isopropyl-iodoamphetamine single-photon emission computed
      tomography.
AB  - OBJECTIVE: To quantitatively evaluate regional cerebral blood flow (rCBF) and
      regional developmental changes during childhood using 123I-N-isopropyl
      iodoamphetamine single-photon emission computed tomography (SPECT) and
      autoradiography. METHODS: We retrospectively analyzed quantitative values of rCBF
      in 75 children (29 girls) aged between 16 days and 178 months (median: 12
      months), whose brain images, including magnetic resonance imaging and SPECT data,
      were normal under visual inspection at Saitama Children's Medical Center between
      2005 and 2015. The subjects had normal psychomotor development, no focal
      neurological abnormalities, and neither respiratory nor cardiac disease at the
      time of examination. Regions of interest were placed automatically using a three
      dimensional stereotactic template. RESULTS: rCBF was lowest in neonates, who had
      greater rCBF in the lenticular nucleus, thalamus, and cerebellum than the
      cerebral cortices. rCBF increased rapidly during the first year of life, reaching
      approximately twice the adult levels at 8 years, and then fell to approximately
      adult levels in the late teenage years. Cerebral cortex rCBF sequentially
      increased in the posterior, central, parietal, temporal, and callosomarginal
      regions during infancy and childhood. CONCLUSIONS: rCBF changed dramatically
      throughout childhood and ranged from lower than adult values to approximately two
      times higher than adult values. It had different trajectories in each region
      during brain development. Understanding this dynamic developmental change is
      necessary for SPECT image evaluation in children.

PMID- 30227936
TI  - Increasing IUD and Implant Use Among Those at Risk of a Subsequent Preterm Birth:
      A Randomized Controlled Trial of Postpartum Contraceptive Counseling.
AB  - OBJECTIVE: To assess the impact of contraceptive counseling on the uptake of long
      acting reversible contraception (LARC), namely, intrauterine devices and the
      contraceptive implant, by 3 months postpartum among women with a recent preterm
      birth. DESIGN: We enrolled patients in a single-blinded, one-to-one, randomized,
      controlled trial to assess the impact of enhanced family planning counseling
      immediately after a viable preterm birth in the inpatient setting. Participants
      received either structured counseling with an emphasis on LARC by a family
      planning specialist (intervention) or routine postpartum care (control). We
      followed participants to the primary outcome of LARC use 3 months postpartum.
      RESULTS: We followed 121 participants for 3 months. Primary outcome data were
      available for 119 participants (61 intervention, 58 control). We found no
      demographic differences between the groups. Participants in the intervention
      group were significantly more likely to use LARC at 3 months postpartum compared
      with controls (51% vs. 31%; p < .05). For every six women who received the
      counseling intervention, one additional woman was using a LARC method at 3
      months. CONCLUSIONS: After a preterm birth, brief LARC-focused, structured
      counseling before hospital discharge significantly increased LARC method use at 3
      months postpartum.

PMID- 30227938
TI  - Anti-MOG antibody encephalitis mimicking neurological deterioration in a case of
      Rett syndrome with MECP2 mutation.
AB  - BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused
      by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, resulting in
      developmental regression after normal development during infancy. Transient
      presentation of many autistic features is also commonly seen in RTT. Anti-myelin
      oligodendrocyte glycoprotein (MOG)-antibody encephalitis is an acquired relapsing
      demyelinating syndrome characterized by a variety of neuroinflammatory symptoms.
      Here, we report a case of anti-MOG antibody encephalitis in a patient with
      genetically confirmed RTT, which mimicked many of the features of RTT. CASE
      REPORT: A three-year-old girl presented with subacute verbal and motor
      dysfunction, along with involuntary movements and marked irritability. Magnetic
      resonance imaging (MRI) revealed extensive white matter lesions, with anti-MOG
      antibodies detected in the serum and cerebrospinal fluid, resulting in an initial
      diagnosis of anti-MOG antibody encephalitis. However, additional testing of the
      MECP2 gene was performed in response to persistent involuntary hand movements in
      combination with progressive verbal and motor deterioration. Sequencing analysis
      revealed a known pathogenic mutation in MEPC2, indicating a concurrent diagnosis
      of RTT. CONCLUSION: Both RTT and anti-MOG antibody encephalitis are rare
      conditions. Similarities in disease presentation suggest that anti-MOG antibody
      encephalitis may mimic many of the symptoms of RTT.

PMID- 30227939
TI  - Contemporary Blood Conservation in Hip and Knee Arthroplasty: Tranexamic Acid is
      an Important Piece of the Puzzle!

PMID- 30227941
TI  - Randomized trial of rivaroxaban versus warfarin in the evaluation of progression
      of coronary atherosclerosis.
AB  - Warfarin, a vitamin K antagonist, is associated with systemic vascular
      calcification. We evaluated whether rivaroxaban (a direct oral factor Xa
      inhibitor with no interaction with vitamin K) will slow the progression in
      coronary plaque volumes compared with warfarin in patients with nonvalvular
      atrial fibrillation using coronary computed tomography angiography.

PMID- 30227940
TI  - RBM17 controls apoptosis and proliferation to promote Glioma progression.
AB  - The splicing factor SPF45 (RBM17) is a well-known component of the spliceosome
      that is involved in alternative splicing. RBM17 is frequently overexpressed in
      many tumors and plays a crucial role in cancer progression and drug resistance.
      However, the role of RBM17 in the development of glioma has not been thoroughly
      elucidated to date. In the present study, we found that RBM17 was overexpressed
      in glioma and that a high level of expression of RBM17 was closely associated
      with a poor prognosis in glioma patients. We investigated the effect of RBM17 on
      apoptosis, cell growth and cell cycle indexes and the activation of apoptosis
      signaling by shRNA in human U87 and U251 glioma cells. The downregulated
      expression of RBM17 mRNA was accompanied by the induction of cell cycle arrest,
      and apoptosis, reduced cell proliferation in the two cell lines, and reduced cell
      survival, as measured by the increased activation of caspase-3, caspase-9, and
      PARP (poly ADP-ribose polymerase). Furthermore, in subcutaneous U87 cell
      xenograft tumors in nude mice, intradermal administration of an shRNA targeting
      RBM17 significantly downregulated RBM17 expression in vivo and was accompanied by
      the suppressed growth of glioma. To the best of our knowledge, our results are
      the first to confirm that RBM17 functions in promoting cell proliferation,
      affecting the cell cycle, and inducing apoptosis in human glioma cells both in
      vitro and in vivo. These results indicate that RBM17 may be a therapeutic target
      in the clinical management of glioma.

PMID- 30227942
TI  - [Assets: from maps to territory. SESPAS Report 2018].
AB  - In recent years, health asset maps have become increasingly important tools in
      the field of health promotion. They are being incorporated into the daily
      practice of many healthcare workers, in individualized care in consultations
      (through social prescription), and in groups or community development processes.
      It is necessary to reflect on how the asset maps are being produced, analyzing
      how the different stages of the process can be involved in their construction.
      The formats in which the data is obtained through the identification of health
      assets are presented, as well as the processes of production of the information,
      participative and evaluated processes, are crucial for the maps to be useful, for
      professionals as well as citizens and institutions.

PMID- 30227943
TI  - Nursing home adoption of the National Healthcare Safety Network Long-term Care
      Facility Component.
AB  - BACKGROUND: Health care-associated infections pose a significant problem in
      nursing homes (NHs). The Long-term Care Facility Component of the National
      Healthcare Safety Network (NHSN) was launched in 2012, and since then, enrollment
      of NHs into NHSN has been deemed a national priority. Our goal was to understand
      the characteristics of NHs reporting to the NHSN compared to other NHs across the
      country. METHODS: To meet this goal, we quantified the characteristics of NHs by
      NHSN enrollment status and reporting consistency using the Certification and
      Survey Provider Enhanced Reporting (CASPER) data linked to NHSN enrollment and
      reporting data. RESULTS: Of the 16,081 NHs in our sample, 262 (or 1.6% of NHs)
      had enrolled in NHSN by the end of 2015; these early adopting facilities were
      more likely to be for-profit and had a higher percentage of Medicare residents.
      By the end of 2016, enrollment expanded by more than 5-fold to 1,956 facilities
      (or 12.2% of NHs). In our analysis, the characteristics of those later adopting
      NHs were more similar to NHs nationally than the early adopters. Specifically,
      bed size and hospital-based facilities were related to both early and late
      adoption of NHSN. CONCLUSIONS: The types of NHs that have enrolled in NHSN have
      changed substantially since the program began. The increased enrollment was
      likely due to the Centers for Medicare & Medicaid (CMS)-funded "C. difficile
      Infection (CDI) Reporting and Reduction Project" that incentivized Quality
      Innovation Network-Quality Improvement Organizations (QIN-QIOs) to support NH
      enrollment and participation in NHSN. Further understanding of a facility's
      ability to enroll in and maintain reporting to NHSN, and how this relates to
      infection prevention staffing and infrastructure in NHs and infection rates among
      NH residents, is needed.

PMID- 30227944
TI  - Changes in the biochemical taste of cytoplasmic and cell-free DNA are major fuels
      for inflamm-aging.
AB  - Inflamm-aging depicts the progressive activation of the innate immune system that
      accompanies human aging. Its role as a disease-predisposing condition has been
      proposed, but its molecular basis is still poorly understood. A wealth of
      literature conveys that, particularly upon stress, nuclear and mitochondrial
      genomes are released into the cytoplasmic and extracellular compartments.
      Cytoplasmic (cy) and cell-free (cf) DNA pools trigger inflammation and innate
      immunity at local and systemic level. In particular, cyDNA plays a crucial role
      in the phenomenon of cell senescence and in the cognate pro-inflammatory
      secretome. Here we propose that changes in a variety of biochemical
      characteristics "tastes" of cy- and cf-DNA (e.g. the amount of 8-oxo-deoxy
      guanosine and 5-methyl-deoxy-cytosine, the proportion of DNA hybridized with RNA)
      potentially affect the capability of these DNA pools to ignite the innate immune
      system. We also underpin that telomeric sequences are major components of the
      cy/cfDNA payload. Telomere shortening, a hallmark of aging, causes the depletion
      of telomeric sequences in cy/cfDNA pool, thus unleashing their potential to exert
      an age-related activation of the innate immune system. Finally, we posit that
      various sources of DNA (extracellular vesicles, the commensal metagenome and
      food) contribute to the cy/cfDNA payloads. We speculate that changes in the
      biochemical "taste" of cy/cfDNA are major modifiers of inflamm-aging.

PMID- 30227945
TI  - Supramolecular complexes for nanomedicine.
AB  - Host-guest interactions studied in supramolecular chemistry have been inspired by
      interactions between enzymes and substrates. Furthermore, most of the
      interactions involved in the cells are based on non-covalent bonds between two or
      more molecules. The common aspects between supramolecular chemistry and medicine
      have led to the development of a "new" area called "supramolecular medicine", in
      which non-covalent interactions and self-assembly processes are applied within
      several medical fields. The object of this Digest is to offer an account of how
      some macrocyclic hosts (e.g. cucurbiturils, cyclodextrins, pillararenes and
      calixarenes) are employed in supramolecular medicine creating new supramolecular
      hydrogels used as biomaterials for human tissue in regenerative medicine, and a
      diagnostic instrument, in-vitro and in-vivo, for the detection of diseases, as
      well as for the investigation of cell morphology.

PMID- 30227946
TI  - Discovery of 3-(4-sulfamoylnaphthyl)pyrazolo[1,5-a]pyrimidines as potent and
      selective ALK2 inhibitors.
AB  - The pyrazolo[1,5-a]pyrimidine LDN-193189 is a potent inhibitor of activin
      receptor-like kinase 2 (ALK2) but is nonselective for highly homologous ALK3 and
      shows only modest kinome selectivity. Herein, we describe the discovery of a
      novel series of potent and selective ALK2 inhibitors by replacing the quinolinyl
      with a 4-(sulfamoyl)naphthyl, yielding ALK2 inhibitors that exhibit not only
      excellent discrimination versus ALK3 but also high kinome selectivity. In
      addition, the optimized compound 23 demonstrates good ADME and in vivo
      pharmacokinetic properties.

PMID- 30227948
TI  - Radiology Needs Robust Dialogue.

PMID- 30227947
TI  - Parasomnia versus epilepsy: An affair of the heart?
AB  - OBJECTIVE: Differential diagnosis between sleep-related epileptic seizures and
      NREM parasomnia remains challenging. Pathophysiological markers to differentiate
      both conditions are needed. Activation of autonomic system is present in arousal
      reactions and epileptic seizures. Our study investigated whether cardiac
      reactivity differed between arousal disorders and sleep-related seizures.
      METHODS: Nocturnal recordings of 50 patients (10 in each group: frontal lobe
      epilepsy [FLE], temporal lobe epilepsy [TLE], nocturnal terror [NT], confusional
      arousal [CA], normal arousals [NA]) were retrospectively selected. Timing of the
      first motor sign and description of behaviours were assessed. Beat-to-beat RR
      intervals (RRI) as well as heart rate variability were analysed over a period of
      60 heartbeats before and after first motor manifestation. The slope and area
      under the curve (AUC) of RRI were calculated. RESULTS: A significant decrease in
      RRI was observed at the onset of all events. Statistical analysis revealed: lower
      RRI in TLE than in other groups; higher slope of RRI in FLE than in NA and TLE,
      and higher AUC in NT and FLE than in TLE, and in NT than in NA. Sleep stage,
      episode duration, vocalization characteristics, lateralized or abnormal posture,
      exploratory behaviour differed between epileptic and parasomnia groups.
      DISCUSSION: Analysis of cardiac reactivity seems to be a useful objective tool,
      together with clinical features, for diagnosing abnormal behaviour during sleep.
      Cardiac reactivity in TLE could reflect epileptic discharge propagation to brain
      areas involved in autonomic control, while FLE and NT might involve a strong non
      specific activation of the sympathetic system.

PMID- 30227949
TI  - Journal Cover Images.

PMID- 30227950
TI  - The Cost-Estimation Department: A Step Toward Cost Transparency in Radiology.

PMID- 30227951
TI  - Long-term hip loading in unilateral total hip replacement patients is no
      different between limbs or compared to healthy controls at similar walking
      speeds.
AB  - Variation in hip joint contact forces directly influences the performance of
      total hip replacements (THRs). Measurement and calculation of contact forces in
      THR patients has been limited by small sample sizes, wide variation in patient
      and surgical factors, and short-term follow-up. This study hypothesised that, at
      long-term follow-up, unilateral THR patients have similar calculated hip contact
      forces compared to controls walking at similar (self-selected) speeds and, in
      contrast, THR patients walking at slower (self-selected) speeds have reduced hip
      contact forces. It was further hypothesised that there is no difference in
      calculated hip contact forces between operated and non-operated limbs at long
      term follow-up for both faster and slower patients. Gait analysis data for THR
      patients walking at faster (walking speed: 1.29 +/- 0.12 m/s; n = 11) and slower
      (walking speed: 0.72 +/- 0.09 m/s; n = 11) speeds were used. Healthy subjects
      constituted the control group (walking speed: 1.36 +/- 0.12 m/s; n = 10). Hip
      contact forces were calculated using static optimisation. There was no
      significant difference (p > 0.31) in hip contact forces between faster and
      control groups. Conversely, force was reduced at heel strike by 19% (p = 0.002),
      toe-off by 31% (p < 0.001) and increased at mid-stance by 15% (p = 0.02) for the
      slower group compared to controls. There were no differences between operated and
      non-operated limbs for the slower group or the faster group, suggesting good
      biomechanical recovery at long-term follow-up. Loading, at different walking
      speeds, presented here can improve the relevance of preclinical testing methods.

PMID- 30227953
TI  - The 20th International Conference on Cytochrome P450: Biochemistry, Biophysics
      and Biotechnology (ICCP450 2017) was held August 27-31, 2017 in Dusseldorf,
      Germany.

PMID- 30227952
TI  - Change in an Urban Food Environment: Storefront Sources of Food/Drink Increasing
      Over Time and Not Limited to Food Stores and Restaurants.
AB  - BACKGROUND: Local food environments include food stores (eg, supermarkets,
      grocery stores, bakeries) and restaurants. However, the extent to which other
      storefront businesses offer food/drink is not well described, nor is the extent
      to which food/drink availability through a full range of storefront businesses
      might change over time. OBJECTIVES: This study aimed to assess food/drink
      availability from a full range of storefront businesses and the change over time
      and to consider implications for food-environment research. DESIGN: Investigators
      compared direct observations from 2010 and 2015. PARTICIPANTS/SETTING: Included
      were all storefront businesses offering foods/drinks on 153 street segments in
      the Bronx, NY. MAIN OUTCOME MEASURES: The main outcome was change between 2010
      and 2015 as determined by matches between businesses. Matches could be strict
      (businesses with the same name on the same street segment in both years) or
      lenient (similar businesses on the same street segment in both years).
      Investigators categorized businesses as general grocers, specialty food stores,
      restaurants, or other storefront businesses (eg, barber shops/beauty salons,
      clothing outlets, hardware stores, laundromats, and newsstands). STATISTICAL
      ANALYSES PERFORMED: Investigators quantified change, specifically calculating how
      often businesses in 2015 were present in 2010 and vice versa. RESULTS: Strict
      matches for businesses in 2015 present in 2010 ranged from 29% to 52%, depending
      on business category; lenient matches ranged from 43% to 72%. Strict matches for
      businesses in 2010 present in 2015 ranged from 34% to 63%; lenient matches ranged
      from 72% to 83%. In 2015 compared with 2010, on 22% more of the sampled street
      segments, 30% more businesses were offering food/drink: 66 vs 46 general grocers,
      22 vs 19 specialty food stores, 99 vs 99 restaurants, 98 vs 56 other storefront
      businesses. CONCLUSIONS: Over 5 years, an urban food environment changed
      substantially, even by lenient standards, particularly among "other storefront
      businesses" and in the direction of markedly greater food availability (more
      businesses offering food on more streets). Failure to consider a full range of
      food/drink sources and change in food/drink sources could result in erroneous
      food-environment conclusions.

PMID- 30227955
TI  - i stands for.

PMID- 30227954
TI  - Transcriptional Co-activator Functions of YAP and TAZ Are Inversely Regulated by
      Tyrosine Phosphorylation Status of Parafibromin.
AB  - YAP and TAZ, the Hippo signal-regulated transcriptional co-activators, play
      crucial roles in morphogenesis and organogenesis. Here we report that the YAP/TAZ
      activities are stimulated upon complex formation with Parafibromin, which
      undergoes tyrosine phosphorylation and dephosphorylation by kinases such as PTK6
      and phosphatases such as SHP2, respectively. Furthermore, TAZ and the Wnt
      effector beta-catenin interact cooperatively with tyrosine-dephosphorylated
      Parafibromin, which synergistically stimulates the co-activator functions of TAZ
      and beta-catenin. On the other hand, YAP is selectively activated through binding
      with tyrosine-phosphorylated Parafibromin, which does not interact with beta
      catenin and thus cannot co-activate YAP and beta-catenin. These findings indicate
      that Parafibromin inversely regulates the activities of YAP and TAZ depending on
      its tyrosine phosphorylation status. They also suggest that YAP and TAZ exert
      their redundant and non-redundant biological actions through mutually exclusive
      interaction with Parafibromin, which is regulated by a balance of kinase and
      phosphatase activities toward Parafibromin.

PMID- 30227956
TI  - Photocurrent Polarity Controlled by Light Wavelength in Self-Powered ZnO
      Nanowires/SnS Photodetector System.
AB  - Self-powered photodetectors are expected to play a crucial role in future nano
      optoelectronic devices owing to their independent and sustainable operation.
      Based on the heterojunction between ZnO nanowires (NWs) and shuttle-like SnS, we
      design a self-powered photodetector exhibiting wide-range photoresponse and
      tunable spectral selectivity. Differently from conventional devices, a wavelength
      induced photocurrent polarity is observed in the ZnO NWs/SnS photodetector, which
      enables the device to distinguish between photons in the UV and visible (VIS)
      regions. This is due to switching of the interfacial modulation by the
      pyroelectric-polarization potential (pyro-potential) inside ZnO NWs and
      thermoelectric-polarization potential (thermo-potential) inside SnS. A
      photocurrent enhancement of 125% and improved responsivity of 364 MUA/W are
      obtained under the pyro-potential upon 690 nm light illumination, whereas
      reversed responsivity of -155 MUA/W is obtained under the thermo-potential upon
      365 nm light illumination. We believe the photocurrent polarity could be useful
      for improving resolution of dynamic light sensing/imaging.

PMID- 30227957
TI  - Controllable Multinary Alloy Electrodeposition for Thin-Film Solar Cell
      Fabrication: A Case Study of Kesterite Cu2ZnSnS4.
AB  - Electrodeposition (ED) technology is a low-cost industrial candidate for solar
      cell fabrication. However, the practical aspects of controlling deposit
      morphology and composition have not been significantly addressed because of the
      complex co-plating variables that still need to be understood for multinary alloy
      ED. This work addresses these practical aspects on how to control composition and
      deposit morphology using co-electrodeposited kesterite alloy precursors as a case
      study. The alloy precursors co-plated under the optimized conditions from a mixed
      thiosulfate-sulfite electrolyte bath show uniform, smooth, and compact film
      morphology as well as uniform distribution of composition, well suited for
      efficient kesterite absorbers, finally delivering a Cu2ZnSnS4 (CZTS) thin-film
      solar cell with 7.4% efficiency based on a configuration Mo/CZTS/CdS/ZnO/aluminum
      doped ZnO. This work underscores that alloy ED, with the advantage of
      controllable composition and morphology, holds promise for low-cost industrial
      manufacture of thin-film solar cells.

PMID- 30227958
TI  - Loss of Deubiquitinase USP1 Blocks Pancreatic beta-Cell Apoptosis by Inhibiting
      DNA Damage Response.
AB  - Impaired pancreatic beta-cell survival contributes to the reduced beta-cell mass
      in diabetes, but underlying regulatory mechanisms and key players in this process
      remain incompletely understood. Here, we identified the deubiquitinase ubiquitin
      specific protease 1 (USP1) as an important player in the regulation of beta-cell
      apoptosis under diabetic conditions. Genetic silencing and pharmacological
      suppression of USP1 blocked beta-cell death in several experimental models of
      diabetes in vitro and ex vivo without compromising insulin content and secretion
      and without impairing beta-cell maturation/identity genes in human islets. Our
      further analyses showed that USP1 inhibition attenuated DNA damage response (DDR)
      signals, which were highly elevated in diabetic beta-cells, suggesting a USP1
      dependent regulation of DDR in stressed beta-cells. Our findings highlight a
      novel function of USP1 in the control of beta-cell survival, and its inhibition
      may have a potential therapeutic relevance for the suppression of beta-cell death
      in diabetes.

PMID- 30227959
TI  - Extracellular Phosphorylation of TIMP-2 by Secreted c-Src Tyrosine Kinase
      Controls MMP-2 Activity.
AB  - The tissue inhibitor of metalloproteinases 2 (TIMP-2) is a specific endogenous
      inhibitor of matrix metalloproteinase 2 (MMP-2), which is a key enzyme that
      degrades the extracellular matrix and promotes tumor cell invasion. Although the
      TIMP-2:MMP-2 complex controls proteolysis, the signaling mechanism by which the
      two proteins associate in the extracellular space remains unidentified. Here we
      report that TIMP-2 is phosphorylated outside the cell by secreted c-Src tyrosine
      kinase. As a consequence, phosphorylation at Y90 significantly enhances TIMP-2
      potency as an MMP-2 inhibitor and weakens the catalytic action of the active
      enzyme. TIMP-2 phosphorylation also appears to be essential for its interaction
      with the latent enzyme proMMP-2 in vivo. Absence of the kinase or non
      phosphorylatable Y90 abolishes TIMP-2 binding to the latent enzyme, ultimately
      hampering proMMP-2 activation. Together, TIMP-2 phosphorylation by secreted c-Src
      represents a critical extracellular regulatory mechanism that controls the
      proteolytic function of MMP-2.

PMID- 30227960
TI  - High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles
      for Glycosylation during Infection of Mammalian and Mosquito Cells.
AB  - Zika virus (ZIKV) infection causes Guillain-Barre syndrome and severe birth
      defects. ZIKV envelope (E) protein is the major viral protein involved in cell
      receptor binding and entry and is therefore considered one of the major
      determinants in ZIKV pathogenesis. Here we report a gene-wide mapping of
      functional residues of ZIKV E protein using a mutant library, with changes
      covering every nucleotide position. By comparing the replication fitness of every
      viral mutant between mosquito and human cells, we identified that mutations
      affecting glycosylation display the most divergence. By characterizing individual
      mutants, we show that ablation of glycosylation selectively benefits ZIKV
      infection of mosquito cells by enhancing cell entry, whereas it either has little
      impact on ZIKV infection on certain human cells or leads to decreased infection
      through the entry factor DC-SIGN. In conclusion, we define the roles of
      individual residues of ZIKV envelope protein, which contribute to ZIKV
      replication fitness in human and mosquito cells.

PMID- 30227961
TI  - Comparison of Early and Long-Term Outcomes After Transcatheter Aortic Valve
      Implantation in Patients with New York Heart Association Functional Class IV to
      those in Class III and Less.
AB  - Our aim was to investigate the impact of a baseline New York Heart Association
      (NYHA) class IV on clinical outcomes of a large real-world population who
      underwent transcatheter aortic valve implantation (TAVI). The primary end points
      were all-cause mortality, cardiovascular mortality, and re-hospitalization,
      evaluated at the longest available follow-up and by means of a 3-month landmark
      analysis. The secondary end points were: change in NYHA class, left ventricular
      ejection fraction, pulmonary pressure and mitral regurgitation. Out of 2,467
      patients, 271 (11%) had a NYHA functional class IV at the admission. The latter
      had higher Society of Thoracic Surgeons (STS) score (9.2% vs 5.5%; p < 0.001)
      compared to NYHA <= III patients, owing to more comorbidities (prior myocardial
      infarction, severe long-term kidney disease, atrial fibrillation, left
      ventricular dysfunction, significant mitral regurgitation, pulmonary
      hypertension). Device success was similar between the two groups (93.7% vs 94.5%;
      p = 0.583). At a median follow-up of 15 months (interquartile range 4 to 36
      months) a lower freedom from primary end points was observed among NYHA IV versus
      NYHA <= III group (survival from all-cause death: 52% vs 58.4%; p = 0.002;
      survival from cardiovascular death: 72.5% vs 76.5%; p = 0.091; freedom from re
      hospitalization: 81.5% vs 85.4%; p = 0.038). However, after adjustment for
      baseline imbalance, NYHA IV did not influence the relative risk of long-term
      primary end points. A 3-month landmark analysis showed that NYHA IV independently
      predicted 3-month all-cause and cardiovascular mortality (hazard ratio: 1.77; 95%
      CI [1.10 to 2.83]; p = 0.018 and hazard ratio: 1.64; 95% CI [1.03 to 2.59]; p =
      0.036, respectively). Instead, after 3-month follow-up NYHA IV did not affect the
      risk of primary end points. A significant improvement of the secondary end points
      was noted in both NYHA IV and NYHA <=<= III groups. In conclusion, the presence
      of NYHA class IV in TAVI candidates was associated to a significant increased
      risk of mortality within 3 months. Patients with baseline NYHA IV who survived at
      3 months had a long-term outcome comparable to that of other subjects. Left
      ventricular systolic function, pulmonary pressure, and mitral insufficiency
      significantly improved after TAVI regardless of baseline NYHA class IV.

PMID- 30227962
TI  - Familial Anomalous Origin of Right Coronary Artery from the Left Coronary Sinus.
AB  - Anomalous origin of a coronary artery from the opposite sinus of Valsalva is a
      rare congenital anomaly. The prevalence of familial clustering of coronary artery
      anomalies is unknown. Here we describe the case of a father and son, both of whom
      presented with major adverse cardiac events due to Anomalous origin of a coronary
      artery from the opposite sinus of Valsalva and both had right coronary artery
      arising from the left coronary cusp with an interarterial course.

PMID- 30227963
TI  - Comparison of Mortality Risk Prediction Among Patients >=70 Versus <70 Years of
      Age in a Cardiac Intensive Care Unit.
AB  - Older adults account for an increasing number of cardiac intensive care unit
      (CICU) admissions. This study sought to determine the predictive value of illness
      severity scores for mortality in CICU patients >=70 years of age. Adult patients
      admitted to the CICU from 2007 to 2015 at one tertiary care hospital were
      reviewed. Severity of illness scores were calculated on the first CICU day. Area
      under the receiver-operator characteristic curve (AUROC) values were used to
      assess discrimination for hospital mortality in patients >=70 versus <70 years of
      age. We included 10,004 patients with a mean age of 67.4 +/- 15.2 years (37.4%
      female); 4,771 patients (47.7%) were >=70 years of age. Patients >=70 years of
      age had greater illness severity and more extensive co-morbidities compared with
      patients <70 years of age. Patients >=70 years of age had higher hospital
      mortality (11.6% vs 6.8%, odds ratio 1.80, 95% confidence interval 1.57 to 2.07,
      p <0.001), with a progressive increase in mortality as a function of decade.
      Severity of illness scores had lower AUROC values for hospital mortality in
      patients >=70 years of age compared with patients <70 years of age (all p <0.05
      by DeLong test). The Braden skin score on CICU admission predicted hospital
      mortality with an AUROC value only slightly lower than these scores. Increasing
      age decade was associated with decreased postdischarge survival by Kaplan-Meier
      analysis (p <0.001 by log-rank). In conclusion, contemporary CICU patients >=70
      years of age have greater illness severity, more co-morbidities and higher
      mortality than patients <70 years of age, yet severity of illness scores are less
      accurate for predicting mortality in CICU patients >=70 years of age, emphasizing
      the need for more effective risk-stratification methods in this population.

PMID- 30227964
TI  - Embolic and Other Adverse Outcomes in Symptomatic Versus Asymptomatic Patients
      With Atrial Fibrillation (from the ORBIT-AF Registry).
AB  - Asymptomatic atrial fibrillation (AF) is being increasingly diagnosed via
      implantable devices, screening, and inpatient telemetry. Management of
      asymptomatic AF is controversial, in part, because the associated risks have not
      been well described. We examined the incidence of major adverse outcomes in
      patients with asymptomatic versus symptomatic AF using Outcomes Registry for
      Better Informed Treatment of Atrial, a nationwide US registry of AF patients. We
      compared stroke and/or non-central nervous system (CNS) embolism, major adverse
      cardiovascular and neurologic events, bleeding, and death in 9,319 asymptomatic
      (defined by European Heart Rhythm Association score = 1 or "no symptoms") versus
      symptomatic patients. Overall, median (interquartile) age was 75 (67 to 82)
      years, 3,944 (42%) were women, and 38% versus 37% were asymptomatic based on
      physician versus patient-reported symptoms. Compared with those with symptoms,
      physician-defined asymptomatic patients were less likely to be woman (35%/47%) or
      be on an antiarrhythmic agent (22%/33%), but were more likely to have permanent
      and/or persistent AF (51%/40%). CHA2DS2-VASc scores did not vary by symptom
      status. After adjustment, risk of first stroke and/or non-CNS embolism (hazard
      ratio [HR] 0.85 [95% confidence interval {CI} 0.63 to 1.16], p = 0.32), major
      adverse cardiovascular and neurologic events (HR 0.88 [95% CI 0.76 to 1.03], p =
      0.11), bleeding (HR 0.85 [95% CI 0.72 to 1.00], p = 0.05), and death (HR 0.99
      [95% CI 0.87 to 1.13], p = 0.88) were similar in asymptomatic (European Heart
      Rhythm Association = 1) and symptomatic AF, respectively. Prospective, randomized
      studies are needed to further define associated adverse events and delineate
      optimal prophylactic therapies in patients with asymptomatic AF.

PMID- 30227965
TI  - Frequency and Significance of High-Degree Atrioventricular Block and Sinoatrial
      Node Dysfunction in Patients With Non-ST-Elevation Myocardial Infarction.
AB  - Characteristics of conduction disorders after ST-elevation myocardial infarction
      (STEMI) have been well described. In contrast, limited data are available on the
      incidence, treatment trends, and prognostic impact of conduction disorders after
      non-ST-elevation myocardial infarction (NSTEMI). Using the National Inpatient
      Sample database, we compared the characteristics and outcomes of conduction
      disorders in patients with a primary diagnosis of STEMI versus NSTEMI between
      2010 and 2014. Conduction disorders were classified into? high-degree AV block
      (HDAVB), consisting of complete AV block or Mobitz type II second-degree AV
      block, and sinoatrial node dysfunction (SND). We identified 135,468 STEMI
      patients and 281,928 NSTEMI patients. In contrast to the STEMI cohort where HDAVB
      was more common than SND (2.4% vs 0.5%), SND was observed more often in the
      NSTEMI cohort, presenting in 2,417 patients (0.9%), followed by HDAVB in 1,745
      patients (0.6%). In patients who developed HDAVB, NSTEMI patients were more
      likely to undergo permanent pacemaker implantation than STEMI patients (30.0% vs
      11.6%; p < 0.001). The rate of permanent pacemaker implantation for SND was
      comparable between STEMI and NSTEMI patients (33.9% vs 30.5%; p = 0.10). In the
      NSTEMI cohort, patients who developed HDAVB had higher in-hospital mortality than
      those without any major conduction disorders (16.6% vs 3.8%; p < 0.001). In
      conclusion, SND was more common than HDAVB in the NSTEMI cohort, in contrast to
      the predominance of HDAVB observed in the STEMI cohort. About one-third of
      patients who developed HDAVB after NSTEMI underwent pacemaker implantation,
      suggesting lower rates of spontaneous resolution of HDAVB, when compared with
      STEMI patients.

PMID- 30227966
TI  - A Checklist for Analyzing Data.

PMID- 30227967
TI  - Re: Aerobic Exercise Combined with Noninvasive Positive Pressure Ventilation
      Increases Serum Brain-Derived Neurotrophic Factor in Healthy Males by Kawazu et
      al.

PMID- 30227968
TI  - Reply.

PMID- 30227969
TI  - Honey can help in herpes simplex gingivostomatitis in children: Prospective
      randomized double blind placebo controlled clinical trial.
AB  - PURPOSE: Herpes simplex gingivostomatitis (HSGS) in children is a common painful
      infectious disease. This study aims to examine the combined efficacy of honey
      with acyclovir suspension compared to acyclovir alone for treating HSGS in young
      children. MATERIAL AND METHODS: This Randomized double blind placebo controlled
      study was conducted from June 2015 to September 2017 in a tertiary referral
      hospital. One hundred children aged 2-8 years with HSGS were randomly classified
      into 2 groups; study group: treated with honey plus oral acyclovir and control
      group: treated with oral acyclovir alone. Severity of oral lesions, Fever, eating
      and drinking ability, pain scores and need for analgesics were compared between 2
      groups on day 3, 5 and 7 after starting treatment. RESULTS: Children receiving
      honey plus acyclovir (i.e. study group) had significantly earlier disappearance
      of herpetic oral lesions; median 3 days vs. 6 days in control group (P = 0.022),
      drooling; 2 days vs. 4 days (P = 0.030) and eating difficulty; 3 days vs. 8 days
      (P = 0.001). Study group also had significantly lower pain scores, better eating
      and drinking ability and significantly less need for analgesics at 3 time-points
      of assessment. Fever disappeared in both groups with no statistically significant
      difference. CONCLUSIONS: The combined use of honey with oral acyclovir can
      produce favorable outcome than acyclovir alone in children with Primary herpetic
      gingivostomatitis.

PMID- 30227971
TI  - Canine Cutaneous Lupus Erythematosus: Newly Discovered Variants.
AB  - As the spectrum of canine cutaneous lupus erythematosus (CLE) variants has
      expanded markedly in the recent 2 decades, veterinarians are encouraged to become
      familiar with the characteristic clinical features of CLE variants to permit
      early diagnosis and appropriate treatment. This article describes the signalment,
      clinical signs, treatment outcome, and laboratory and histopathology findings of
      2 new canine CLE variants, generalized discoid lupus erythematosus and
      mucocutaneous lupus erythematosus.

PMID- 30227970
TI  - Update on Allergen Immunotherapy.
AB  - Allergen immunotherapy has been used for many years in dogs and cats and is the
      only specific treatment of atopic dermatitis that changes the patho-mechanisms of
      disease by stimulating allergen tolerance. Subcutaneous administration of
      allergens is the most commonly used administration route, typically in increasing
      concentrations (induction period) followed by long-term injection of allergen
      extract (maintenance therapy). Rush protocols with an abbreviated induction
      period have been reported and shown to be safe in dogs. More recently, oro
      mucosal and intralymphatic administration of allergens has been evaluated in
      dogs. Approximately two-thirds of patients show good to excellent improvement of
      clinical signs.

PMID- 30227972
TI  - Feline Pemphigus Foliaceus.
AB  - Feline pemphigus foliaceus is an uncommon skin disorder in cats but still the
      most common autoimmune skin disorder seen in this species. It is a crusting
      dermatosis involving the ears, head, paws, and ungual folds primarily. Although
      cytology is helpful in supporting a diagnosis, biopsy of pustules or crusts for
      histopathology is required for a definitive diagnosis. Therapy has evolved over
      the years as we have learned more about the different ways cats respond to drugs
      and as new drugs became available. Most cats will respond to proper therapy,
      although it may be needed long term for control.

PMID- 30227974
TI  - Value assessment of disease-modifying therapies for Relapsing-Remitting Multiple
      Sclerosis: HTA evidence from seven OECD countries.
AB  - This study systematically compares HTA recommendations on a number of disease
      modifying therapies for patients with Relapsing-Remitting Multiple Sclerosis. We
      analysed publicly available HTA reports for nine medicine-indication pairs across
      seven OECD countries using a methodological framework enabling systematic
      analysis of HTA recommendations. The analysis was conducted based on a number of
      value dimensions, including clinical and economic variables, as well as several
      other dimensions of value beyond cost-effectiveness. The material was
      qualitatively and quantitatively coded following the different stages of HTA
      decision-making process. Fifty-seven medicine-indication pairs were assessed
      across the study countries. Of those, eight medicine indication-pairs reported
      diverging HTA recommendations. Although HTA recommendations were based on the
      same evidence submitted in most cases, significant variations were identified in
      interpretation and acceptance of evidence resulting in different uncertainties
      raised and different ways of addressing them. Uncertainties arose both in terms
      of the clinical and the economic evidence, including the design of key trials or
      the data quality in economic models. Beyond costs and effects, additional
      dimensions of value had an impact in the direction of recommendations, however
      with different magnitude across countries. We show that there is heterogeneity
      across countries in HTA for evaluating DMTs for RRMS with a lack of standardised
      methods in evaluating clinical and economic evidence and the use of social value
      judgments to inform decision-making.

PMID- 30227973
TI  - The Functional Connectivity Between the Nucleus Accumbens and the Ventromedial
      Prefrontal Cortex as an Endophenotype for Bipolar Disorder.
AB  - BACKGROUND: Alterations in functional connectivity between the nucleus accumbens
      (NAcc) and frontal cortices have been previously associated with the presence of
      psychiatric syndromes, including bipolar disorder (BD). Whether these alterations
      are a consequence or a risk factor for mental disorders remains unresolved.
      METHODS: This study included 35 patients with BD, 30 nonaffected siblings of
      patients with BD, and 23 healthy control subjects to probe functional
      connectivity at rest between NAcc and the rest of the brain in a cross-sectional
      design. Blood oxygen level-dependent time series at rest from NAcc were used as
      seed region in a voxelwise correlational analysis. The strength of the
      correlations found was compared across groups after Fisher's Z transformation.
      RESULTS: We found increased functional connectivity between the NAcc and the
      ventromedial prefrontal cortex-comprising mainly the subgenual anterior cingulate
      in patients compared with healthy control subjects. Participants at increased
      genetic risk but yet resilient-nonaffected siblings-showed functional
      connectivity values midway between the former two groups. CONCLUSIONS: Our
      results are indicative of the potential for the connectivity between NAcc and the
      ventromedial prefrontal cortex to represent an endophenotype for BD.

PMID- 30227975
TI  - New professional roles and patient satisfaction: Evidence from a European survey
      along three clinical pathways.
AB  - This paper reports the results of an empirical analysis exploring the impact of
      new professions (eg a physician associate) and new professional roles on patient
      experiences of and satisfaction with care. A sub set of data from a patient
      survey conducted as part of the MUNROS programme of work was used. The overall
      survey aim was to describe and quantify the use of new professionals and new
      roles for established health care professionals other than medical doctors, in
      primary and secondary care sectors in three care pathways in nine European
      countries Ordered logit models were used to investigate the association between:
      (1) patient satisfaction with the last visit; (2) with their care provider; (3)
      with the information provided and a set of covariates explaining the involvement
      of new professional roles in three clinical pathways: type 2 diabetes, heart
      disease and breast cancer. For patients with breast cancer, high levels of
      satisfaction are associated with the involvement of new professions/professional
      roles in the provision of conditions specific education and monitoring. For
      patients with heart disease, the involvement of new professions/professional
      roles is likely to have a negative impact on satisfaction. For patients with Type
      2 diabetes results are ambivalent. Patients belonging to countries experiencing
      innovative models of healthcare delivery and with high levels of involvement of
      new professions/professional roles are generally more satisfied. In conclusion,
      the introduction of new professions does not affect patient satisfaction
      negatively, therefore introducing new health professional roles is a pursuable
      strategy from a patient satisfaction perspective, at least for breast cancer and
      type 2 diabetes.

PMID- 30227976
TI  - Does adjuvant concurrent or sequential chemotherapy increase the radiation
      related toxicity of vaginal brachytherapy for endometrial cancer patients?
AB  - PURPOSE: To compare radiation toxicity in endometrial cancer patients treated
      with adjuvant vaginal brachytherapy (VBT) vs. VBT with concurrent chemotherapy
      (CCT) or sequential chemotherapy (SCT) METHODS: We retrospectively analyzed 131
      patients with endometrial cancer treated with VBT without external beam radiation
      therapy. Toxicities were graded according to the Common Terminology Criteria for
      Adverse Events v4.03. CCT was defined as VBT delivered between the first and last
      cycle of chemotherapy (CT); SCT was defined as VBT delivered before or after CT.
      RESULTS: Median followup was 36 months, with a 3-year survival rate of 88%. Of
      the 131 patients, 92 were treated with VBT alone, 34 with VBT and CCT, and 5 with
      VBT and SCT. The most common toxicity was vaginal stricture, with 30 (22.9%)
      patients affected. The distribution of toxicities was vaginal 28%, urinary 12%,
      rectal 11%, and fatigue 5%; none greater than Grade 2. Compared with patients
      treated with VBT alone, the addition of CT did not increase the chance of vaginal
      stricture formation (p = 0.84). The difference in system-specific toxicities
      between treatment modalities was not statistically significant. CONCLUSION: The
      most common pelvic toxicity from VBT is vaginal stenosis with other toxicities
      being infrequent and generally Grade 1. The addition of CT in a sequential or
      concurrent fashion did not increase the rate of pelvic toxicity from VBT alone.

PMID- 30227977
TI  - Accelerated partial breast irradiation with perioperative multicatheter
      interstitial brachytherapy-A feasibility study.
AB  - PURPOSE: To assess the feasibility of high-dose-rate perioperative multicatheter
      interstitial brachytherapy to deliver accelerated partial breast irradiation
      (APBI) in selected patients with early breast cancer. METHODS AND MATERIALS:
      Perioperative multicatheter interstitial brachytherapy for APBI has been used at
      our department since 2012 for patients with low-risk breast cancer. Interstitial
      catheters were inserted perioperatively via hollow needles immediately following
      tumorectomy with sentinel node biopsy. APBI started on Day 6 after surgery. The
      prescribed dose was 34 Gy (10 fractions of 3.4 Gy bid). Hormonal therapy was
      prescribed in all cases. RESULTS: Between June 2012 and December 2017, 125
      patients were scheduled for APBI. Of these, APBI was not performed in 12 patients
      (9.6%) due to adverse prognostic factors identified on the definitive biopsy. We
      observed wound dehiscence in 2/113 cases (1.8%), inflammatory complications
      requiring antibiotics in 7/113 cases (6.2%), transient Grade I radiodermatitis in
      6/113 patients (4.4%), and seroma which resolved spontaneously in 3/113 patients
      (2.7%). With median followup of 39 months (range 3.3-75.3) no relapses were
      observed. No late complications in Radiation Therapy Oncology Group Grade 3 or
      higher were documented. Cosmetic outcome in patients with followup > 2 years was
      excellent or good in 92%. CONCLUSION: Our preliminary results show that the
      perioperative multicatheter interstitial high-dose-rate brachytherapy for APBI in
      selected patients with early breast cancer is feasible. This treatment schedule
      reduces treatment duration, spares the patients of repeated anesthesia, and
      enables precise application of the afterloading tubes under direct visual
      control.

PMID- 30227979
TI  - Intelligibility of Long-Distance Emergency Calling.
AB  - OBJECTIVE: This study examined the identification of emergency calling across
      distance without electronic assistance, as in the event of an electric grid black
      out or being stranded in the wilderness. METHODS: Fifteen participants were
      callers and forty-one participants were recorders. Ten callers underwent an hour
      long training in how to produce vocally healthy loud phonation, as well as,
      yodeled calls. Outdoors, the callers individually called out a set of single and
      multisyllable words, either yodeled or nonyodeled. Recorders and sound level
      meters were placed at four distances from the caller and were asked to select the
      called word as part of a closed-set identification task. RESULTS: Distances
      greater than 100 m had significantly reduced call identification. Caller sex did
      not yield statistically significant differences in call identification at any
      distance. Participation in training only yielded a statistically significant
      difference in call identification at 170 m. For distances greater than 25 m,
      multisyllabic words were significantly better identified than single syllable
      words. Nonyodeled calls had a higher score by a statistically significant amount
      for ranges above 50 m than yodeled calls. Yodeled calls were found to have a
      greater sound level than nonyodeled calls at greater distances. The study results
      were consistent with the inverse square law. CONCLUSIONS: Even a small amount of
      training can provide improvement in identification at long distances.
      Multisyllable words provide better identification than single syllable
      identification at distances beyond 25 m. Future research is recommended, focusing
      particularly on the amount of training necessary to improve identification and
      environmental effects on identification.

PMID- 30227978
TI  - A revised dosimetric characterization of 60Co BEBIG source: From single-source
      data to clinical dose distribution.
AB  - PURPOSE: Although the dosimetric characterization of 60Co BEBIG source can be
      found in several literature studies, the data sets show major discrepancies and
      the lack of uncertainty analyses. This study tried to determine an accurate
      dosimetric data set for this source using Monte Carlo (MC) simulations along with
      detailed uncertainty analysis. To explore how different dosimetric data sets can
      make changes in practical situations, clinical dose distributions based on our
      results were compared with the dose distributions derived from Granero et al. and
      consensus data sets. METHODS AND MATERIALS: The MC simulations were performed
      with Monte Carlo N-Particle eXtended code (MCNPX) version 2.6.0 and the TG-43
      parameters were estimated adhering to the American Association of Physicists in
      Medicine (AAPM) and European SocieTy for Radiotherapy and Oncology (ESTRO) 229
      report. The dose rate distributions for single-source and two typical clinical
      cases, including one intracavitary and one interstitial, were calculated using an
      in-house code on the basis of the TG-43 formalism. RESULTS: The total
      uncertainties for water dose rate on source transverse axis at 1 cm and 5 cm, air
      kerma strength, and dose rate constant were evaluated to be 0.10%, 0.09%, 0.04%,
      and 0.11%, respectively. Meaningful differences were found for the interstitial
      case in which 22% of clinical target volume (CTV) showed differences from +/-1%
      to +/-10% or even larger. CONCLUSIONS: The MC uncertainty was derived about 16
      times smaller than the typical MC component stated in TG-138, partly because of
      large number of histories and partly because the spectra of 60Co and also its
      photons' attenuation coefficients are adequately accurate. The results showed
      that in the clinical situations, the applicator geometry and the superposition of
      single-source dose distributions can reduce the differences observed between
      several data sets.

PMID- 30227980
TI  - Original Research: Aerosolized Lidocaine: Effective for Safer Arousal After
      Suspension Laryngoscopy.
AB  - AIM: To examine the systemic and local effects of the lidocaine on the larynx and
      trachea which is applied after the end of the surgery and through various
      application methods. STUDY DESIGN: Randomized controlled prospective study.
      METHOD: The study is composed of patients who underwent suspension laryngoscopy
      (SL) for benign laryngeal diseases (cysts, polyp, granuloma, etc) and American
      Society of Anesthesiologists (ASA) I, between January 2017 and January 2018. The
      patients were randomly divided into 3 groups. In the first group nothing is
      applied at the end of the surgery and called as control group, second group
      received 7 pufs of aerosolized 10% lidocaine solution (70 mg) over larynx and
      trachea and third group received cotton swaps that impregnated in 1 ml of 20 mg
      lidocaine solution over surgical area for 1 minutes. Operation and arousal times,
      heart rate and mean arterial blood pressure levels were noted and compared. Also
      laryngospasm, cough, and agitation scores were obtained during arousal. RESULTS:
      64 patients were included in the study. Laryngospasm was not observed in any of
      the patients. In group 2 (aerosolized lidocaine group), patients' blood pressure
      remained similar while increased in other groups (P < 0.05). Agitation scores
      were significantly lower in group 2 compared to the other groups (P = 0.012).
      Cough reflex is observed less in group 2 but result was not statistically
      significant (P = 0.13) CONCLUSION: The usage of aerosolized lidocaine after
      suspension laryngoscopy is very effective in blocking the stimulation of superior
      laryngeal nerve and sympathetic nerves which were responsible for the pressor
      reflexes. The inhibition of these reflexes before or during arousal could secure
      a safer arousal.

PMID- 30227981
TI  - Web-Based Perceived Present Control Intervention for Voice Disorders: A Pilot
      Study.
AB  - OBJECTIVE: Voice disorders are common and negatively affect various life domains
      such as occupational functioning and emotional well-being. Perceived present
      control, a factor that is amenable to change, may reduce the effect of voice
      disorders on these outcomes. This pilot study aimed to (1) establish the
      feasibility, usability, and acceptability of a web-based perceived present
      control intervention for individuals with voice disorders and (2) gather
      preliminary data on the effectiveness of the intervention. This study is the
      first to assess whether a web-based psychological intervention would decrease
      self-reported voice handicap in this population. METHODS: Participants (N = 20)
      were recruited from an otolaryngology clinic at a large, Midwest university and
      the surrounding urban community, and completed a 3-week web-based intervention
      that incorporated psychoeducation and written exercises on increasing perceived
      present control. RESULTS: Supporting feasibility, the intervention components had
      high completion rates (75%-95%). Most participants planned to continue the
      perceived control exercises after study completion and would recommend the
      intervention to others, demonstrating usability and acceptability. There was a
      significant decrease in self-reported voice handicap (Voice Handicap Index-10)
      from pretest (M = 18.38, standard deviation = 4.41) to post-test (M = 15.22,
      standard deviation = 4.55) with a large effect size (within-group d = -0.86, P <
      0.05). CONCLUSIONS: Focusing on perceived present control as a teachable skill
      may be a useful addition to voice disorder treatment armamentarium. Future
      studies will incorporate a comparison group and larger sample sizes to assess
      further the role of perceived present control interventions in voice care.

PMID- 30227982
TI  - Ecotoxicological evaluation of gilthead seabream (Sparus aurata) exposed to the
      antibiotic oxytetracycline using a multibiomarker approach.
AB  - Oxytetracycline (OTC) is an antibiotic widely used in human and veterinary
      medicines. Since the primary toxicity occurs mainly at molecular/biochemical
      levels, the study of different biological responses corresponds to a sensitive
      and crucial approach. The aim of the present study was to assess the toxic
      effects of OTC in gilthead seabream (Sparus aurata) through the use of
      multibiomarkers and elucidate about the possible toxicological mechanisms
      involved. S. aurata were acutely (96 h: 0.04-400 MUg/L) and chronically (28 days:
      0.0004-4 MUg/L) exposed to OTC. Detoxification, antioxidant defense, lipid
      peroxidation, genotoxicity, neurotransmission and energy metabolism biomarkers
      were evaluated. OTC impaired the detoxification pathways and caused peroxidative
      damage and genotoxicity. The relevance of the here-obtained data is high, since
      significant effects were recorded for levels already reported to occur in the
      wild, meaning that environmentally-exposed marine organisms (including those
      cultured at fish farms) are not completely exempt of risks posed by OTC.

PMID- 30227983
TI  - Distribution and composition of floating macro litter off the Azores archipelago
      and Madeira (NE Atlantic) using opportunistic surveys.
AB  - The distribution and composition of macro litter floating around oceanic islands
      is poorly known, especially in the North Atlantic. Due to its isolated location
      at the fringe of the North Atlantic subtropical gyre, the Azores archipelago has
      recently been proposed as a potential retention zone for floating litter. To
      further investigate this assumption, opportunistic surveys from pole-and-line
      tuna fishing boats were performed from 2015 to 2017 to document (1) the
      distribution and (2) the composition of the floating macro litter present off the
      Azores and Madeira islands. Among the 2406 visual transects, 482 floating debris
      were recorded and were mainly composed of general plastic user items (48%),
      plastic packaging (21%) and derelict fishing gears (18%). Average number of
      debris per transect was 0.19 +/- 0.5, with a total number ranging between 0 and 5
      items per transect. For the majority of transects (84%), no debris was observed,
      13% of the transects contained a single item, and only 3% contained more than one
      item. Although debris between 2.5 and 5 cm were recorded, 93% of the debris were
      larger than 5 cm. The GLMs showed strong effect of the observer (p < 0.001) and
      the standardized densities accounting for the observer bias were higher (1.39 +/-
      0.14 items.km-2) than the observed densities (0.78 +/- 0.07 items.km-2). Debris
      densities were however relatively low and tended to aggregate around the Central
      group of the Azores (standardized mean: 0.90 +/- 0.20 items.km-2). Our findings
      therefore suggest that most of the debris might originate from far away land
      based sources and from fishing activities. This study highlights the potential of
      fisheries observer programs to obtain cost-effective information on floating
      macro debris that are essential to support the implementation of the European
      Marine Strategy Framework Directive.

PMID- 30227984
TI  - T2 mapping MRI technique quantifies carotid plaque lipid, and its depletion after
      statin initiation, following acute myocardial infarction.
AB  - BACKGROUND & AIMS: A recently-validated, highly-sensitive T2 mapping magnetic
      resonance (MRI) technique accurately quantifies carotid plaque lipid. The aims of
      this study were to determine: (i) the extent of carotid plaque lipid in patients
      with acute coronary syndromes (ACS); (ii) the effects of initiation of high
      intensity statin on plaque lipid content and (iii) whether plaque lipid content
      is related to standard or 'functional' blood lipid measurements. METHODS: Statin
      naive subjects presenting with ACS underwent carotid artery MRI at 3 T scanner to
      quantify plaque lipid. Patients were subsequently commenced on high dose statin
      as part of clinical care and underwent a second MRI after three months. Plaque
      composition was measured using objective semi-automated techniques. RESULTS: 23
      out of 24 patients had measurable lipid. Three months after statin initiation
      there was a significant reduction in carotid lipid percentage [from 10.3% (7.2
      14.2) to 7.4% (5.4-10.0), p = 0.002] and a significant increase in fibrous
      percentage [from 83.3% +/- 6.6-85.5% +/- 4.8, p = 0.039]. None of the studied
      functional blood biomarkers were related to either baseline carotid plaque lipid
      content or its propensity to change with statin treatment. CONCLUSIONS: T2
      mapping demonstrated depleted carotid plaque lipid following the initiation of
      high-intensity statin treatment. Standard or 'functional' blood biomarkers were
      dissociated from plaque lipid content or changes with treatment. These findings
      further reinforce the importance of disease characterisation over risk factor
      assessment. Subject to clinical trial findings, quantification of plaque lipid
      may provide the basis for an approach to identify patients suitable for intensive
      lipid reduction regimes.

PMID- 30227985
TI  - Multi-organ quantitative MRI for the assessment of liver disease - A whole much
      more than the sum of its parts.

PMID- 30227986
TI  - Applying precision to the design and interpretation of dietary trials.

PMID- 30227987
TI  - Smartphone-based multicolor bioluminescent 3D spheroid biosensors for monitoring
      inflammatory activity.
AB  - Whole-cell biosensors present many advantages, including being able to monitor
      the toxicity and bioavailability of chemicals; cells grown in traditional 2D
      cultures, however, do not reproduce the complexity of in vivo physiology. In the
      last years, 3D cell-culture models have garnered great attention due to their
      capability to better mimic in vivo cellular responses to external stimuli,
      providing excellent model living organisms. In order to obtain a predictive,
      sensitive, and robust yet low-cost 3D cell biosensor, we developed a smartphone
      based bioluminescent 3D cell biosensor platform for effect-based analysis. We
      exploited the Nuclear Factor-kappa B (NF-kB) signal transduction pathway, which
      is induced by several types of stressors and is involved in the regulation of
      cell-cycle/growth, inflammation, apoptosis, and immunity. The smartphone-based
      biosensor relies on immobilized HEK293 spheroids genetically engineered with
      powerful red- and green-emitting luciferases utilized as inflammation and
      viability reporters. It provides a limit of detection for Tumor Necrosis Factor
      (TNFalpha) of 0.15 +/- 0.05 ng/mL and could be a useful tool to initially screen
      environmental samples or other compounds on-site, especially for additional more
      accurate chemical analyses.

PMID- 30227989
TI  - Low-dose UVB therapy is comparable with conventional UVB phototherapy for
      treatment of vitiligo: A pilot study.

PMID- 30227990
TI  - 30-day all-cause readmission rates among a cohort of individuals with rare
      conditions.
AB  - BACKGROUND: There is a need to examine health care utilization of individuals
      with the rare conditions muscular dystrophies, spina bifida, and fragile X
      syndrome. These individuals have a greater need for health care services,
      particularly inpatient admissions. Prior studies have not yet assessed 30-day all
      cause readmission rates. OBJECTIVE: To estimate 30-day hospital readmission rates
      among individuals with three rare conditions. HYPOTHESIS: Rare conditions
      patients will have a higher 30-day all-cause readmission rate than those without.
      METHODS: Data from three sources (2007-2014) were combined for this case-control
      analysis. A cohort of individuals with one of the three conditions was matched
      (by age in 5 year age groups, gender, and race) to a comparison group without a
      rare condition. Inpatient utilization and 30-day all-cause readmission rates were
      compared between the two groups. Logistic regression analyses compared the odds
      of a 30-day all-cause readmission across the two groups, controlling for key
      covariates. RESULTS: A larger proportion in the rare condition group had at least
      one inpatient visit (46.1%) vs. the comparison group (23.6%), and a higher 30-day
      all-cause readmission rate (Spina Bifida-46.7%, Muscular Dystrophy-39.7%, and
      Fragile X Syndrome-35.8%) than the comparison group (13.4%). Logistic regression
      results indicated that condition status contributed significantly to differences
      in readmission rates. CONCLUSIONS: Higher rates of inpatient utilization and 30
      day all-cause readmission among individuals with rare conditions vs. those
      without are not surprising, given the medical complexity of these individuals,
      and indicates an area where unfavorable outcomes may be improved with proper care
      coordination and post discharge care.

PMID- 30227988
TI  - Sexual dimorphism in the neural impact of stress and alcohol.
AB  - Alcohol use disorder is a widespread mental illness characterized by periods of
      abstinence followed by recidivism, and stress is the primary trigger of relapse.
      Despite the higher prevalence of alcohol use disorder in males, the relationship
      between stress and behavioral features of relapse, such as craving, is stronger
      in females. Given the greater susceptibility of females to stress-related
      psychiatric disorders, understanding sexual dimorphism in the relationship
      between stress and alcohol use is essential to identifying better treatments for
      both male and female alcoholics. This review addresses sex differences in the
      impact of stressors on alcohol drinking and seeking in rodents and humans. As
      these behavioral differences in alcohol use and relapse originate from sexual
      dimorphism in neuronal function, the impact of stressors and alcohol, and their
      interaction, on molecular adaptations and neural activity in males and females
      will also be discussed. Together, the data reviewed herein, arising from a
      symposium titled "Sex matters in stress-alcohol interactions" presented at the
      Fourth Volterra Conference on Stress and Alcohol, will highlight the importance
      of identifying sex differences to improve treatments for comorbid stress and
      alcohol use disorder in both sexes.

PMID- 30227991
TI  - DDT and its metabolites could contribute to the aetiology of chronic kidney
      disease of unknown aetiology (CKDu) and more studies are a priority.

PMID- 30227992
TI  - Age of transfused red blood cells and health outcomes in two surgical cohorts.
AB  - RATIONALE: Red blood cells (RBC) undergo morphologic and biochemical changes
      during storage which may lead to adverse health risks upon transfusion. In prior
      studies, the effect of RBC age on health outcomes has been conflicting. We
      designed the study to assess the effects of RBC units' storage duration on health
      outcomes specifically for hospitalized patients undergoing hip fracture surgery
      or coronary artery bypass grafting (CABG) surgery. METHODS: Using International
      Classification of Diseases (ICD) 9 codes, hip fracture surgery and CABG surgery
      patients, who received RBC transfusions between 2008 and 2013, were
      retrospectively identified from the electronic medical records system. Hip
      fracture surgery and CABG cohorts were sub-divided into 3 blood age groups based
      upon RBC unit age at the time of transfusion: young blood (RBC units stored less
      than or equal to 14 days), old blood (RBC units were stored for greater than or
      equal to 28 days), or mixed blood for the remaining patients. Outcome variables
      were 30-day, 90-day, and inpatient mortality as well as hospital length of stay.
      RESULTS: A total of 3,182 patients were identified: 1,121 with hip fractures and
      2,061 with CABG. Transfusion of old blood was associated with higher inpatient
      mortality in the hip fracture surgery cohort (OR 166.8, 95% CI 1.067-26064.7, p =
      0.04) and a higher 30-day mortality in the CABG cohort (OR 4.55, 95% CI 1.01
      20.49, p = 0.03). CONCLUSIONS: Transfusing RBC units stored for greater than or
      equal to 28 days may be associated with a higher mortality for patients
      undergoing hip fracture or CABG.

PMID- 30227993
TI  - The value of Stanford integrated psychosocial assessment for transplantation
      (SIPAT) in prediction of clinical outcomes following left ventricular assist
      device (LVAD) implantation.
AB  - BACKGROUND: The Stanford integrated psychosocial assessment for transplantation
      (SIPAT) is a validated psychosocial evaluation tool in the transplant population.
      OBJECTIVE: We evaluated SIPAT in predicting post-left ventricular assist device
      (LVAD) outcomes, including cumulative re-admissions, driveline infections, pump
      malfunction, pump thrombosis, gastrointestinal bleeding, major bleeding, stroke
      and right ventricular failure. METHODS: This retrospective study included 50 LVAD
      patients at an academic institution in the United States who had a pre-implant
      SIPAT score during the years 2015-2017. Patients were split into two groups based
      on SIPAT score, separating a "excellent"/"good" from a "minimally
      acceptable"/"poor" candidate. Poisson regression, using SIPAT as both a
      categorical and continuous variable, was used to compare the incidence rates of
      the primary outcome of cumulative re-admissions and secondary outcomes of LVAD
      complications. RESULTS: The patient cohort was predominantly male 93.5% vs 89.4%
      (p = 0.629) with a median age of 67.0 vs 58.0 years (p = 0.037), planned
      destination therapy 48.4% vs 68.4% (p = 0.242) and median LVAD follow-up time of
      241 vs 379 days (p = 0.10) in the low- and high- SIPAT groups, respectively.
      SIPAT was not a significant predictor for cumulative re-admissions, but there was
      an association between higher SIPAT scores and major bleeding. CONCLUSION: In
      this single-center retrospective study, SIPAT did not predict cumulative re
      admissions. Further study is required to validate SIPAT before clinical
      implementation.

PMID- 30227994
TI  - Single-port laparoscopic herniorrhaphy using a two-hooked cannula device with
      hydrodissection.
AB  - BACKGROUND: Laparoscopic percutaneous extraperitoneal closure (LPEC) with
      variable devices seems to be one of the most simple and reliable methods. We
      described our modifications of single-port laparoscopic herniorrhaphy using an
      inner two-hooked cannula device with preperitoneal hydrodissection. PATIENTS AND
      METHODS: 1568 children with 2114 inguinal hernias were treated by single-port
      LPEC. Under laparoscopic visualization, the two-hooked cannula device carrying a
      silk suture was inserted at the point of the internal ring and could be readily
      kept in an identical path. The hernia orifice was completely lassoed
      extraperitoneally by the suture with the assistance of hydrodissection. Any huge
      hernias of more than 1.5 cm were repaired with the incorporation of medial
      umbilical fold flap as reinforcement. RESULTS: All hernia repairs were
      successfully performed by LPEC. 1022 patients had unilateral inguinal hernia
      repair, and 546 patients underwent bilateral inguinal hernia repair. Of these,
      additional medial umbilical flap reinforcement was necessary in 68 cases, and an
      assisted grasping instrument was used in 19 cases owing to omental adhesion or
      sliding hernia. Mean operating times for unilateral and bilateral inguinal hernia
      repairs were 9.8 +/- 2.1 min and 13.6 +/- 2.2 min, respectively. There were no
      operative complications. Two recurrences and three hydroceles were observed
      during 6 to 30 months of follow-up. CONCLUSIONS: One-puncture LPEC using the two
      hooked cannula device with preperitoneal hydrodissection has proved to be a safe
      and effective procedure with excellent cosmetic results. LEVEL OF EVIDENCE: IV.

PMID- 30227995
TI  - An investigation on clinical differences between congenital pulmonary airway
      malformation and bronchial atresia.
AB  - BACKGROUND/PURPOSE: Differences in clinical features between congenital pulmonary
      airway malformation (CPAM) and bronchial atresia (BA) have not yet been clearly
      described. METHODS: We retrospectively reviewed 112 patients with a pathological
      diagnosis of CPAM or BA. The clinical parameters were statistically analyzed
      between these diseases. RESULTS: Seventy-one patients received prenatal diagnosis
      and 41 received postnatal diagnosis. The percentage of prenatal diagnosis was
      significantly higher in CPAM patients (84% vs 50%, p < 0.001). Among patients
      with prenatal diagnosis, the backgrounds were not different between the two
      diseases except for the number of Caesarean sections (81% vs 9%, p < 0.0001). The
      numbers of patients that underwent fetal interventions and emergent neonatal
      surgery were higher in CPAM (51% vs 15%, p < 0.01 and 76% vs 12%, p < 0.0001),
      although there was no statistical difference in survival rate (86% vs 97%, p =
      0.2). In patients receiving postnatal diagnosis, pneumonia was the primary
      symptom in most BA patients, whereas respiratory distress was the major symptom
      in patients with CPAM. Age at presentation of the primary symptom was
      significantly older in BA patients (4.2 years vs 1.2 years, p < 0.005).
      CONCLUSION: CPAM and BA have distinct clinical features in terms of therapeutic
      and natural history. Careful imaging evaluation and pathological analysis can
      lead to an accurate diagnosis of BA. TYPE OF STUDY: Prognostic study. LEVEL OF
      EVIDENCE: Level II. This study is categorized as a "Prognostic Study" with LEVEL
      III of Evidence.

PMID- 30227996
TI  - A comparison of aortic root measurements by echocardiography and computed
      tomography.
AB  - OBJECTIVES: The aim of the study is to evaluate an optimal way to assess the
      dimensions of the aortic root and each of the sinuses of Valsalva and examine how
      a single measurement in 1 plane (echocardiography or 2-dimensional computed
      tomography) can underestimate the maximum dimension of the aortic root. METHODS:
      Computed tomography and transthoracic echocardiography images of the aortic root
      and ascending aorta of 112 patients were analyzed. The minimum and maximum aortic
      root dimensions, the root perimeter, and the total area of all 3 sinuses of
      Valsalva were measured on a plane perpendicular to the long axis of the aorta
      using 3-dimensional multiplanar reconstruction. Moreover, the maximum root
      dimension was compared with the measurements obtained from the echocardiography
      and 2-dimensional computed tomography angiography measurements. RESULTS: The
      difference in the measurements of the minimum and maximum root dimension was 5.4
      +/- 3.2 mm (range, 0-21 mm, P < .0001) and was significantly larger in patients
      with bicuspid aortic valves compared with those with tricuspid valves (6.3 +/- 4
      mm, range, 0-21 mm vs 4.9 +/- 2.6 mm, range, 0-15 mm, P = .036). The maximum root
      dimension measured in 3-dimensional multiplanar reconstruction (49.1 +/- 9.0 mm)
      differed significantly from the root dimension measured in transthoracic
      echocardiography in the parasternal long-axis view (44.8 +/- 8.4 mm) and 2
      dimensional computed tomography (axial plane: 45.5 +/- 9.0 mm, coronal plane:
      46.1 +/- 8.8 mm, sagittal plane: 45.1 +/- 8.9 mm) (P < .001). CONCLUSIONS: The
      difference in the measurements of the minimum and maximum aortic root dimensions
      is significant and may exceed 20 mm, especially in patients with bicuspid aortic
      valves. Therefore, aortic root dimensions can be significantly underestimated
      with the measurement (echocardiography, computed tomography angiography)
      performed in only 1 plane.

PMID- 30227997
TI  - Sepsis-3: More specific is better?

PMID- 30227998
TI  - Innovation series.

PMID- 30227999
TI  - Discovery of natural flavonoids as activators of Nrf2-mediated defense system:
      Structure-activity relationship and inhibition of intracellular oxidative
      insults.
AB  - Continuous overproduction of reactive oxygen species (ROS), termed as oxidative
      stress, plays a crucial role in the onset and progression of many human diseases.
      Activation of nuclear transcription factor erythroid 2-related factor (Nrf2) by
      small molecules could eliminate ROS, and thus block the pathogenesis of oxidative
      stress-induced diseases. In this study, a natural flavonoid library was
      established and tested for their potential Nrf2 inducing effects. Based on QR
      inducing effect of flavonoids, their structure-activity relationship (SAR) on
      Nrf2 induction was summarized, and twenty flavonoids were firstly identified to
      be potential activators of Nrf2-mediated defensive response. Then, 7-O
      methylbiochanin A (7-MBA) was further investigated for its capability on the Nrf2
      activation and prevention against oxidative insults in human lung epithelial
      cells. Further studies indicated that 7-MBA activated Nrf2 signaling pathway and
      protected human lung epithelial Beas-2B cells against sodium arsenite [As(III)]
      induced cytotoxicity in an Nrf2-dependent manner. Activation of Nrf2 by 7-MBA
      upregulated intracellular antioxidant capacity, which was produced by enhancement
      of Nrf2 stabilization, blockage of Nrf2 ubiquitination, as well as Nrf2
      phosphorylation by mitogen-activated protein kinase (MAPK), protein kinase C
      (PKC), protein kinase R-like endoplasmic reticulum kinase (PERK), and
      phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). Taken together, 7-MBA is a
      novel isoflavone-type Nrf2 activator displaying potential preventive effect
      against oxidative damages in human lung epithelial cells.

PMID- 30228000
TI  - Andrographolide derivative as STAT3 inhibitor that protects acute liver damage in
      mice.
AB  - Sustained activation of the Janus kinase-signal transducers and activators of
      transcription (JAK-STAT) pathway contributed to the progression of cancer and
      liver diseases. STAT3 signaling inhibitor has been extensively investigated for
      pharmacological use. We synthesized a series of andrographolide derivatives, and
      characterized their activity against STAT3 signaling pathway both in vitro and in
      the CCl4-induced acute liver damage mice model. Among these derivatives, compound
      24 effectively inhibited phosphorylation and dimerization of STAT3 but not its
      DNA binding activity. Compound 24 significantly ameliorated carbon tetrachloride
      induced acute liver damage in vivo without changing mice body weight. Treatment
      with 24 attenuated hepatic pathologic damage and promoted hepatic proliferation
      and activation of STAT3. Compound 24 inhibited elevated expression of alpha
      smooth muscle actin and serum pro-inflammatory cytokines downstream of STAT3 but
      not those factors that are regulated by NF-kappaB or SMADs. In summary, our
      results suggest that compound 24 may serve as a potential therapeutic agent for
      the treatment of hepatic damage or a liver protection agent via regulating STAT3
      activation.

PMID- 30228001
TI  - Structure-activity relationship of novel (benzoylaminophenoxy)phenol derivatives
      as anti-prostate cancer agents.
AB  - The androgen receptor (AR) is a ligand-inducible transcription factor belonging
      to the nuclear receptor superfamily, and is a target molecule for development of
      drugs to treat prostate cancer. However, AR antagonists in clinical use, such as
      flutamide (3a) and bicalutamide (4), encounter resistance after several years of
      hormone therapy, predominantly due to mutations of AR. Thus, although some new
      generation AR antagonists have been developed, novel types of AR antagonists are
      still required to treat drug-resistant prostate cancer. We previously reported a
      novel (benzoylaminophenoxy)phenol derivative 10a, which is structurally distinct
      from conventional AR antagonists. Here, we systematically examined the structure
      activity relationship of (benzoylaminophenoxy)phenol derivatives on the
      inhibitory activity on the prostate cancer cell proliferations. We found that the
      4-[4-(benzoylamino)phenoxy]phenol backbone is important for anti-prostate cancer
      activity. Introduction of a small substituent at the 2 position of the central
      benzene ring (B ring) increases the activity. Among the synthesized compounds,
      19a and 19b exhibited the most potent inhibitory activity toward
      dihydrotestosterone-induced proliferation of several androgen-dependent cell
      lines, SC-3 (wild-type AR), LNCaP (T877A AR), and 22Rv1 (H874Y AR), but
      interestingly also inhibited proliferation of AR-independent PC-3 cells. These
      compounds, which have a different pharmacophore from conventional AR antagonists,
      are promising drug candidates for the treatment of prostate cancer.

PMID- 30228002
TI  - Facial Palsy: Diagnostic and Therapeutic Management.

PMID- 30228003
TI  - You're Never Fully Dressed Without a Smile.

PMID- 30228004
TI  - Describing the mandible in patients with craniofacial microsomia based on
      principal component analysis and thin plate spline video analysis.
AB  - Craniofacial microsomia (CFM) is most often described as a unilateral
      malformation of derivatives of the first and second branchial arches. The
      mandible has been classified using several classification systems. However, all
      are based on two-dimensional imaging. The aim of this study was to mathematically
      describe the deformed mandible based on principal component analysis (PCA) in a
      three-dimensional way. This may aid in defining the flaws in existing surgical
      corrections of the mandible through the identification of the differences in
      shape compared with a normal mandible in a holistic view with the help of videos.
      Forty-three homologous landmarks were defined to describe a mandible with CFM.
      Computed tomography scans of 22 patients and 30 controls were marked manually.
      The changes in shape between the mandibles were visualized using videos. A
      lateral rotation with increase in posterior rotation of the condyle due to
      shortening of the condyle-gonial height and a longitudinal rotation with outward
      bending of the mandibular angle were noted on the affected side, as well as an
      inward bending of the angle on the unaffected side. Due to the compensatory
      remodelling of the mandible on the unaffected side, one could suggest that CFM is
      never truly unilateral.

PMID- 30228005
TI  - MRI assessment of the bone adjacent to giant cell tumours and its association
      with local recurrence after intralesional curettage.
AB  - AIM: To assess the tumour border surrounding giant cell tumour of the bone (GCTB)
      using magnetic resonance imaging (MRI) and investigate its association with local
      recurrence. MATERIALS AND METHODS: Sixty-nine GCTBs in proximal tibiae and distal
      femurs were studied. The pathological basis of the paintbrush border sign was
      explored. Expression of Ki-67, matrix metalloproteinase-9 (MMP-9), vascular
      endothelial growth factor (VEGF), receptor activator of nuclear factor-kappa B
      (RANK), and RANK ligand (RANKL) in GCTBs were investigated using
      immunohistochemistry. Patients treated with intralesional curettage were analysed
      retrospectively to investigate the prognostic role of the paintbrush border sign.
      The differences between rates were tested using the chi-square test or Fisher's
      exact test, as appropriate. RESULTS: The paintbrush border sign correlated well
      with infiltrative margins. The expression of MMP-9 was associated with the
      paintbrush border sign, and positively correlated with RANKL and VEGF expression.
      GCTBs with the paintbrush border sign had a higher rate of local recurrence
      (76.19 versus 20.59%, p<0.05). The paintbrush border sign was more common in
      proximal tibiae, and positively correlated with cystic change. The paintbrush
      border signs were detected at T1-weighted imaging, but the sign was only evident
      in four cases on T2-weighted imaging. CONCLUSION: Pathologically, the paintbrush
      border sign correlates well with invasion of the bone around GCTB. MMP-9 might
      play a key role in the formation of penetrating irregular margins. The paintbrush
      border sign is revealed as a risk factor for local recurrence of GCTB. Sagittal
      T1-weighted imaging is crucial to diagnose the paintbrush border sign.

PMID- 30228006
TI  - Clinical Potential of Immobilized Liquid Interfaces: Perspectives on Biological
      Interactions.
AB  - Immobilized liquid (IL) surface coatings are an emerging technology that provide
      to materials the ability to repel complex biological fluids and hold promise in
      medical applications to prevent biological fouling, especially in the context of
      preventing medical device-induced thrombosis, fibrosis, and biofilm formation.
      However, little is known about the biological interactions of the IL with
      proteins and cells, and an increased understanding is critical for optimal device
      application, function, and successful clinical translation. Here, we review
      existing clinical and biological knowledge of the liquids used in these surface
      coatings, recent developments in understanding the biological interactions of IL
      coatings, and future directions and challenges for the clinical translation of
      this new class of IL surface coatings.

PMID- 30228007
TI  - A critical evaluation of the use of gas chromatography- and high performance
      liquid chromatography-mass spectrometry techniques for the analysis of microbial
      metabolites in human urine after consumption of orange juice.
AB  - The present study compared and validated two analytical methods, HPLC-HRMS, and
      GC-MS using MSTFA as derivatization agent, for the analysis of microbiota-derived
      phenolic acids and aromatic compounds accumulating in urine, collected over a 24
      h period after the consumption of 500 mL of orange juice. In addition,
      purification procedures using SDB-L and HLB solid phase cartridges were compared
      when HPLC-HRMS technique was used. Both HPLC-HRMS and GC-MS methodologies were
      successfully validated in terms of specificity, sensitivity, limit of detection
      and quantification, recovery and matrix effects. HPLC-HRMS, unlike GC-MS, does
      not require sample derivatization prior to analysis. GC-MS was not suitable for
      the analysis of phenolic sulfate and glucuronide metabolites because of their
      lack of volatility. These phase II metabolites could, however, be analysed by
      HPLC-HRMS which, as a consequence, provided more detailed and complete
      information on the phenolic compounds derived from microbiota-mediated
      degradation of orange juice (poly)phenols. Furthermore, the use of SDB-L and HLB
      cartridges for sample purification prior to HPLC-HRMS analysis is suitable for
      free phenolics and glucuronide metabolites but not sulfate derivatives. These
      findings highlight that the use of an inappropriate analytical protocol can
      adversely affect studies on the bioavailability of dietary (poly)phenols in which
      microbiota-derived phenolic catabolites play an important role.

PMID- 30228008
TI  - Dispersive liquid-liquid microextraction based on liquid anion exchanger for the
      direct extraction of inorganic anions.
AB  - For the first time, the possibility of the use of liquid anion exchangers in
      dispersive liquid-liquid microextraction for the direct extraction of some
      inorganic anions (nitrite, nitrate, and iodide) was evaluated. In this technique,
      chloroform containing a liquid anion exchanger (trioctylamine) was used as
      extractant. The mixture of the extractant and disperser solvent (acetonitrile)
      was injected into the acidic sample solution. The protonated trioctylamine formed
      a water-insoluble salt with the inorganic anions (analytes). After the phase
      separation and stripping of the analytes from the extractant, the analytes were
      determined by liquid chromatography with UV detection. Various parameters
      affecting the extraction efficiency were investigated. Under the optimum
      conditions, broad linear dynamic ranges, with determination coefficients (r2)
      higher than 0.998, and enrichment factors between 94 and 244 were obtained. The
      limits of detection and quantification were in the range of 0.1-0.5 and 0.4-1.7
      MUg L-1, respectively. Also, the values of intra- and inter-day relative standard
      deviations were 3.5-5.8% and 5.5-7.8%, respectively. Various real water samples
      including sea, tap, river, spring and mineral water were analyzed by the method.
      The method was sensitive, simple, inexpensive and capable of the simultaneous
      extraction and determination of the selected inorganic anions.

PMID- 30228009
TI  - Magnetic solid phase extraction of sulfonamides based on carboxylated magnetic
      graphene oxide nanoparticles in environmental waters.
AB  - A magnetic nano-adsorbent material was prepared by functionalizing carboxylic
      group onto the granule surface of magnetic graphene oxide nanoparticles (CMGO),
      using in-situ co-precipitating method. The surface morphology was characterized
      by SEM and TEM. The CMGO was selected as the adsorbent for the magnetic solid
      phase extraction (MSPE) of sulfonamides (SAs) from environmental water samples,
      and the eluted analytes were determined by ultra high performance liquid
      chromatography-tandem mass spectrometry (UHPLC-MS/MS). A series of experimental
      parameters were optimized to improve the extraction efficiency such as amount of
      CMGO, extraction time, pH, ionic strength of the sample solution and desorption
      conditions. When the pH of water sample was 4.00, the extraction recoveries (ERs)
      for SAs were over 82.0% with 15.0 mg CMGO adsorption for 20 min. Under the
      optimized extraction conditions, linear range was obtained with coefficients of
      determination (R2)>=0.9983. The limits of detection for this proposed method were
      in the range of 0.49-1.59 ng/L, and the enrichment factors were 1320-1702 for
      eight SAs. The newly developed method was successfully applied to the analysis of
      trace SAs in real-world water samples, which provided satisfactory ERs in the
      range of 82.0-106.2% with RSDs less than 7.2%. Overall, it shows a great
      potential for the concentration of trace amine organic pollutions in complex
      matrices.

PMID- 30228010
TI  - Stroke in Pregnancy and Review of Current Literature: Arterial Spin-Labeling MRI
      Can Identify the Presence and Intensity of Collateral Circle.
AB  - Diagnosis and treatment of acute ischemic stroke is challenging during pregnancy.
      We present a diagnostic strategy in a pregnant woman with suspect of acute
      stroke. We perform magnetic resonance with arterial spin labeling sequence, an X
      ray and contrast medium safe perfusion technique. Arterial spin labeling can
      detects collateral vessels in patient with acute ischemic stroke. Demonstrating
      collateral vessels is relevant for better understanding prognosis and for
      improving the diagnostic assessment in pregnancy.

PMID- 30228012
TI  - Saffron for staining the anterior lens capsule.

PMID- 30228011
TI  - Ceritinib Alone for Crizotinib-naive Versus Crizotinib-pretreated for Management
      of Anaplastic Lymphoma Kinase-rearrangement Non-Small-cell Lung Cancer: A
      Systematic Review.
AB  - Ceritinib shows a promising efficacy in patients with anaplastic lymphoma kinase
      (ALK)-rearrangement non-small-cell lung cancer (NSCLC). The present systematic
      review determined the whole body and intracranial effectiveness and safety of
      ceritinib in crizotinib-naive versus crizotinib-pretreated regimens in ALK
      rearrangement NSCLC. A comprehensive search of databases, including PubMed,
      EMBASE, Ovid, Web of Science, and COCHRANE, was performed to identify clinical
      trials in English-language journals. We estimated the pooled progression-free
      survival (PFS) and overall response rate (ORR) for ceritinib in whole body and
      intracranial responses to find differences between crizotinib-naive and
      crizotinib-pretreated regimens. The intracranial disease control rate in both
      crizotinib-naive and crizotinib-pretreated regimens was also estimated. The
      pooled efficacy parameters were as follows: ORR, 56.9% (95% confidence interval
      [CI], 53.6%-60.1%); PFS, 8.26 months (95% CI, 6.18-11.07 months); intracranial
      ORR, 41.3% (95% CI, 35.3%-47.6%); and intracranial disease control rate, 79.8%
      (95% CI, 73.8%-84.7%). The pooled ceritinib for crizotinib-naive showed a trend
      toward greater ORR and longer PFS compared with ceritinib for crizotinib
      pretreated (68.9% and 14.62 months vs. 48.2% and 6.32 months, respectively). The
      intracranial ORR for ceritinib as the initial regimen was 50.6% compared with
      33.6% for crizotinib-pretreated. The discontinuation and dose reduction rates
      were 3.1% and 38.4%, respectively. The most common grade 3/4 adverse effects were
      increased alanine aminotransferase (25.5%), increased gamma-glutamyltransferase
      (12.6%), and increased aspartate aminotransferase (11.1%). Ceritinib is an
      effective agent for both crizotinib-naive and crizotinib-pretreated patients with
      locally advanced or metastatic ALK-rearranged NSCLC. Ceritinib has significant
      activity in crizotinib-naive patients with brain metastases.

PMID- 30228013
TI  - In vivo evaluation of a new hydrophobic acrylic intraocular lens in the rabbit
      model.
AB  - PURPOSE: To evaluate the uveal and capsular biocompatibility as well as
      positioning stability of a new hydrophobic acrylic intraocular lens (IOL) in vivo
      in the rabbit model and compare it with a commercially available IOL. SETTING:
      John A Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN:
      Experimental study. METHODS: Fifteen New Zealand rabbits had the new test IOL
      (Clareon CNA0T0) implanted in one eye and a control IOL (Acrysof SN60WF)
      implanted in the contralateral eye. The test IOL is manufactured from a new
      hydrophobic acrylic material incorporating ultraviolet blocker and blue light
      filter. Its design is based on the control IOL's platform. The rabbits were
      followed up with weekly slitlamp evaluations, which assessed inflammatory
      reactions as well as capsular bag opacification. Anterior chamber depth was
      measured at 1 and 4 weeks post-implantation (high-frequency ultrasound). After 4
      weeks, the rabbits were killed humanely and the eyes were enucleated. The
      anterior segment was evaluated from the posterior or Miyake-Apple view, and was
      then processed for complete histopathology. RESULTS: There were no statistically
      significant differences between test and control eyes in terms of postoperative
      inflammation and capsular biocompatibility, including posterior capsule
      opacification (P = .34, paired t test), and anterior capsule opacification (P =
      .53, paired t test), as observed during clinical and pathological evaluation. In
      vivo axial positioning for the test IOL was comparable to the control IOL and
      stable over time (P = .531 versus P = .788). CONCLUSIONS: The new IOL showed
      biocompatibility and stability comparable to the control IOL.

PMID- 30228014
TI  - Corneal crosslinking without epithelial removal.
AB  - PURPOSE: To evaluate the effect of riboflavin-ultraviolet (UV)-A corneal
      crosslinking (CXL) without epithelial removal on ectatic corneal disease.
      SETTING: Woolfson Eye Institute, Atlanta, Georgia, USA. DESIGN: Prospective
      observational study. METHODS: Patients were treated with a new riboflavin
      formulation without epithelial removal, then exposed to UV light (365 nm) at 4
      mW/cm2 with on-off cycling for 30 minutes. Uncorrected (UDVA) and corrected
      (CDVA) distance visual acuities, maximum corneal curvature (maximum keratometry
      [Kmax]), total higher-order aberrations (HOAs), and coma were measured at 3, 6,
      12, and 24 months postoperatively. Progression was defined as an increase of more
      than 1 diopter (D) in Kmax and loss of more than 1 line of CDVA. RESULTS: Five
      hundred twelve eyes of 308 patients with keratoconus or forme fruste keratoconus
      and 80 eyes of 55 patients with ectasia after laser in situ keratomileusis
      (LASIK) were treated with the new riboflavin formulation without epithelial
      removal; 229 patients received bilateral treatments, 95 of which were
      simultaneous. The mean UDVA and CDVA improved by 1 to 1.5 Snellen lines at 1 and
      2 years postoperatively (P < .0001). Mean Kmax decreased by 0.48 D at 2 years
      postoperatively (P = .0002). Mean total HOAs and coma decreased by 36% (P <
      .0001) and 37% (P = .0002), respectively, at 2 years postoperatively. Kmax
      decreased more than 1 D in three times as many eyes as it increased more than 1 D
      (P < .0001). No eyes progressed, and there was no loss of effect between 1 and 2
      years postoperatively. No vision-threatening events were observed. Pain typically
      resolved within 24 hours, and visual acuity returned to preoperative levels in 1
      to 2 days. CONCLUSION: Epithelium-on CXL using this new protocol halted the
      progression of keratoconus and ectasia after LASIK. It was safer and provided
      more rapid visual recovery than CXL with epithelial removal, allowing routine
      bilateral, simultaneous treatment.

PMID- 30228015
TI  - A fatal blood concentration of 5-APB.
AB  - For the new psychoactive drug 5-(2-aminopropyl) benzofuran (5-APB), very limited
      knowledge is available regarding lethal concentrations. We present a case and
      report the post mortem blood concentration of a fatal outcome for a 25 year old
      man related to the consumption of 5-APB. After intake, he became unconscious and
      stopped breathing. Cardiopulmonary resuscitation was started without success.
      After 30min he was declared dead at the scene. During autopsy, whole blood from
      the femoral vein was collected and screened for a wide range of medicinal drugs
      and drugs of abuse. 5-APB was initially identified by ultra high performance
      liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS)
      and subsequently confirmed by using ultra high performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS). The only toxicological findings were
      ethanol 0.6g/L, tetrahydrocannabinol (THC) 0.0024mg/L and 5-APB 0.86mg/L. The
      cause of death was attributed to intake of 5-APB. Only one previous report of a
      fatal 5-APB concentration as the main toxicological agent exist in the
      literature, and the present concentration indicated that 5-APB could be lethal in
      lower concentrations than previously reported.

PMID- 30228016
TI  - Insights into adsorption behaviour of binary liquid mixtures in porous media
      using fast field cycling NMR.
AB  - Fast field cycling, FFC, NMR relaxometry experiments are reported in the
      frequency range of 10 kHz-40 MHz to characterise the adsorption behaviour of
      cyclohexane:THF (non-polar:polar) and THF:methanol (polar:polar) binary liquid
      mixtures adsorbed on a gamma-alumina surface of catalytic interest. Laplace
      inversion of the relaxation rate data is employed to identify the chemical
      species in the binary mixture. In both systems studied, the more polar molecule
      preferentially interacts with the surface compared to the co-imbibed species. The
      relaxation rate data were analysed to explore the relative influences of surface
      dynamics and surface accessibility on the observed relaxation rates. For both
      binary systems, the change in relaxation behaviour with composition is
      interpreted as a change in the surface accessibility of each species caused by a
      micro-phase separation at the pore surface.

PMID- 30228017
TI  - Fast spatially-resolved T2 measurements with constant-gradient CPMG.
AB  - Speed of acquisition is paramount for the application of magnetic resonance to
      flow experiments through porous rocks. One popular method for imaging core floods
      is the spatially resolved T2 experiment which can separate fluids either by their
      viscosity contrast or by doping one fluid with a relaxation agent. Existing
      techniques for spatial-T2 may suffer from long acquisition times and eddy
      currents due to the pulsing of magnetic field gradients. Here, we propose a
      constant gradient method for 1d spatially-resolved T2 which embraces the speed of
      frequency encoding techniques and avoids eddy currents by the absence of any
      gradient ramps during the radio frequency (r.f.) pulse train. We provide the
      operating envelope for this kind of experiment, which is restricted due to the
      slice selectivity of the r.f. pulses in the presence of the magnetic field
      gradient. Additionally, we show that the effects of self-diffusion and the mixing
      of T1 and T2 contributions are manageable. As an illustration, we have applied
      this technique to an enhanced oil recovery experiment. The two fluid phases were
      tracked without any doping and with a time resolution of 40 s. In this case, the
      increased time resolution allowed us to observe dynamic flow phenomena such as
      fluid fingering and the calculation of the velocity of the fluid displacement
      fronts.

PMID- 30228018
TI  - Subclinical atherosclerosis in patients with cyanotic congenital heart disease.
AB  - INTRODUCTION: Survival in patients with cyanotic congenital heart disease (CCHD)
      has improved dramatically. The result is an ageing population with risk of
      acquired heart disease. Previous small uncontrolled studies suggested that these
      patients are protected against the development of atherosclerosis. To test this
      hypothesis, we sought to determine the prevalence of subclinical atherosclerosis
      in a larger population of patients with CCHD. METHOD: We compared the prevalence
      of subclinical atherosclerosis in adult CCHD patients from Denmark, Sweden,
      Norway and Australia, with that in age-, sex-, smoking status-, and body mass
      index matched controls. Coronary artery atherosclerosis was assessed on computed
      tomography with coronary artery calcification (CAC) score. Subclinical
      atherosclerosis was defined by CAC-score > 0. Carotid artery atherosclerosis was
      evaluated using ultrasound by measuring carotid plaque thickness (cPT-max) and
      carotid intima media thickness (CIMT). Lipid status was evaluated as an important
      atherosclerotic risk factor. RESULTS: Seventy-four patients with CCHD (57% women,
      median age 49.5 years) and 74 matched controls (57% women, median age 50.0 years)
      were included. There were no differences between the groups in: CAC-score > 0
      (21% vs. 19%, respectively; p = 0.8), carotid plaques (19% vs. 9%, respectively;
      p = 0.1), cPT-max (2.3 mm vs. 2.8 mm, respectively; p = 0.1) or CIMT (0.61 mm vs.
      0.61 mm, respectively; p = 0.98). And further no significant differences in
      lipoprotein concentrations measured by ultracentrifugation. CONCLUSION: Young
      adults with CCHD have similar cardiovascular risk factor profiles and measures of
      subclinical atherosclerosis, compared with controls. Given their increasing life
      expectancies, athero-preventive strategies should be an important part of their
      clinical management.

PMID- 30228019
TI  - Exercise testing in hypertrophic cardiomyopathy: A pathophysiological goldmine
      with protean clinical implications.

PMID- 30228020
TI  - Left ventricular myocardial dysfunction in arrhythmogenic cardiomyopathy with
      left ventricular involvement: A door to improving diagnosis.
AB  - BACKGROUND: Diagnostic Task Force Criteria (TFC) for arrhythmogenic
      cardiomyopathy (AC) exhibit poor performance for left dominant forms. TFC only
      include right ventricular (RV) dysfunction (akinesia, dyssynchrony, volumes and
      ejection fraction). Moreover, cardiac magnetic resonance imaging (CMRI)
      assessment of left ventricular (LV) dyssynchrony has hitherto not been described.
      Thus, we aimed to comprehensively characterize LV CMRI behavior in AC patients.
      METHODS: Thirty-five AC patients with LV involvement and twenty-three non
      affected family members (controls) were enrolled. Feature-tracking analysis was
      applied to cine CMRI to assess LV ejection fraction (LVEF), LV end-systolic and
      end-diastolic volume indexes, strain values and dyssynchrony. Regions with more
      frequent strain and dyssynchrony impairment were also studied. RESULTS: Radial
      dyssynchrony and LVEF were selected (sensitivities 54.3% and 48.6%, respectively
      at 100% specificity), with a threshold of 70 ms for radial dyssynchrony and 48.5%
      for LVEF. 71.4% of patients exceeded these thresholds (31.4% both, 22.9% only
      dyssynchrony and 17.1% only LVEF). Considering these cut-off values as a novel
      combined criterion, 30% of patients with 'borderline' or 'possible' AC following
      2010 TFC would move to a 'definite' AC diagnosis. Strain was globally impaired
      whereas dyssynchronous regions were more often apical and located at the
      inferolateral wall. CONCLUSIONS: Mirroring the RV evaluation, we suggest
      including LVEF and LV dyssynchrony to improve the diagnosis of AC. Two
      independent mechanisms can be claimed in AC patients with LV involvement: 1)
      decreased myocardial deformation with global LV affectation and 2) delayed
      myocardial contraction at localized regions.

PMID- 30228022
TI  - Frequent intragenic microdeletions of elastin in familial supravalvular aortic
      stenosis.
AB  - BACKGROUND: Supravalvular aortic stenosis (SVAS) is a congenital heart disease
      affecting approximately 1:25,000 live births. SVAS may occur sporadically, be
      inherited in an autosomal dominant manner, or be associated with Williams-Beuren
      syndrome, a complex developmental disorder caused by a microdeletion of
      chromosome 7q11.23. ELN on 7q11.23, which encodes elastin, is the only known gene
      to be recurrently mutated in less than half of SVAS patients. METHODS: Whole
      exome sequencing (WES) was performed for seven familial SVAS families to identify
      other causative gene mutations of SVAS. RESULTS: Three truncating mutations and
      three intragenic deletions affecting ELN were identified, yielding a diagnostic
      efficiency of 6/7 (85%). The deletions, which explained 3/7 of the present
      cohort, spanned 1-29 exons, which might be missed in the course of mutational
      analysis targeting point mutations. The presence of such deletions was validated
      by both WES-based copy number estimation and multiplex ligation-dependent probe
      amplification analyses, and their pathogenicity was reinforced by co-segregation
      with clinical presentations. CONCLUSIONS: The majority of familial SVAS patients
      appear to carry ELN mutations, which strongly indicates that elastin is the most
      important causative gene for SVAS. The frequency of intragenic deletions
      highlights the need for quantitative tests to analyze ELN for efficient genetic
      diagnosis of SVAS.

PMID- 30228021
TI  - Incidence and predictors of bleeding in ACS patients treated with PCI and
      prasugrel or ticagrelor: An analysis from the RENAMI registry.
AB  - OBJECTIVES: To evaluate "real life" incidence and independent predictors of major
      bleeding defined in ACS patients treated with PCI and current standard
      antithrombotic therapy with prasugrel or ticagrelor. METHODS AND RESULTS: The
      RENAMI project is a multicenter retrospective observational registry enrolling
      4424 patients with ACS treated with PCI and prasugrel or ticagrelor plus aspirin.
      Primary endpoint was MACE (major adverse cardiovascular events). Secondary
      endpoints included each component of MACE, cardiovascular death (CV death),
      recurrence of ACS (reACS) and stroke. Eighty three (1.8%) patients developed out
      of hospital major bleedings after 14.1 +/- 6.2 months. These patients had higher
      rates of MACE (14.5% vs 4.4%; p = 0.001) and of all-cause death (11% vs 2.1%; p <
      0.001). Independent predictors of major bleeding were age >75 years (OR 2.00; 95%
      CI 1.18-3.41; p = 0.010) and female sex (OR 1.66; 95% CI 1.02-2.70; p = 0.041).
      BARC 3-5 bleeding was independently associated with all-cause mortality (OR 3.46;
      95% CI 1.64-7.31; p 0.001). CONCLUSION: In ACS patients treated with PCI and
      ticagrelor or prasugrel, BARC 3-5 bleedings despite being uncommon negatively
      impacted on prognosis. Old and female patients are at increased risk, offering
      clinical indications for tailoring dual antiplatelet therapy.

PMID- 30228023
TI  - Analysis of 50 cases of solid pseudopapillary tumor of pancreas: Aggressive
      surgical resection provides excellent outcomes.
AB  - INTRODUCTION: This study reports the clinicopathological characteristics and the
      perioperative and long-term treatment outcomes after aggressive surgical
      resection in solid pseudopapillary tumor (SPT) of the pancreas performed at a
      high volume center for pancreatic surgery in India. MATERIALS AND METHODS: We
      analyzed a prospectively maintained database of the patients operated for SPT at
      Tata Memorial Hospital, India over a period of 11 years from February 2007 to
      February 2018. RESULTS: Fifty consecutive patients operated for SPT, during the
      study period were included. The median age at presentation was 24 years. Majority
      of the patients (43/50) were female (86%). Disease was predominantly localized in
      the head and uncinate process of pancreas (66%). Median tumor size was 7.7 cm
      (Range 1.6-15 cm). Tumor extent was radiologically defined as borderline
      resectable or locally advanced in 48% (n = 24) patients. Forty-six major
      pancreatic resections were performed, which included 10 (21%) vascular
      resections, 2 synchronous liver metastasectomies, 1 multi visceral resection and
      5 total pancreaticosplenectomies. Five of these resections were reoperations in
      patients deemed inoperable on exploration at other centers. R0 resection was
      achieved in 47 patients (98%). Postoperative major morbidity was 19% and there
      was no mortality. At a median follow-up of 29 months (Range, 1-121 months), all
      patients were alive without any recurrence. CONCLUSION: Aggressive complete
      surgical resection of SPT achieves excellent long-term survival. Surgery,
      especially for large and borderline resectable tumors, can be potentially complex
      and should be performed at high-volume centers to provide the best chance of
      cure.

PMID- 30228024
TI  - Knockdown of HOXC6 inhibits glioma cell proliferation and induces cell cycle
      arrest by targeting WIF-1 in vitro and vivo.
AB  - BACKGROUND: Homeobox C6 (HOXC6) is one of several HOXC genes and is frequently
      overexpressed in multiple cancers. However, the function and mechanism of HOXC6
      in glioma remain unclear. METHODS: The expression level of HOXC6 and its
      relationship with prognosis in glioma were determined through the TCGA database.
      The expressions of HOXC6 mRNA in glioblastoma tissues and normal brain tissues
      were detected by qRT-PCR and Western blot. To explore the role of HOXC6 in
      glioma, a lentiviral vector that expressed HOXC6-shRNA was constructed and
      transfected into glioma U87 cells. The expression levels of HOXC6 and WNT
      inhibitory factor 1 (WIF-1) in the glioma U87 cells after transfection with HOXC6
      shRNA were measured by real-time PCR and Western blot. CCK-8, colony formation
      and EdU assays were used to measure the effects of HOXC6 on U87 cell
      proliferation, and flow cytometry was used to monitor the changes in the cell
      cycle and cell apoptosis after transfection with HOXC6-shRNA. Xenograft tumors
      were examined in vivo for the carcinogenic effects and prognostic value of HOXC6
      in glioma tissues. RESULTS: In this study, HOXC6 was highly expressed in human
      glioma tissues, and a high expression of HOXC6 was associated with poor prognosis
      in GBM patients. We demonstrated that HOXC6 was highly expressed in human GBM
      tissues and three glioma cell lines. The knockdown of HOXC6 expression
      significantly inhibited the proliferation and colony formation ability of U87
      cells by blocking cell cycle progression in the G0/G1 phase and induced
      apoptosis. In addition, we found that the mRNA and protein levels of WIF-1 were
      substantially increased after transfection with HOXC6-shRNA compared with Ctrl
      shRNA in vitro. Consistent with the results of the in vitro assays, the xenograft
      assay and immunohistochemistry also demonstrated that in response to HOXC6
      inhibition, the tumor growth and Ki-67 expression level were inhibited and the
      WIF-1 expression was increased in vivo. CONCLUSIONS: In conclusion, the results
      of the current study indicate that HOXC6 promotes glioma U87 cell growth through
      the WIF-1/Wnt signaling pathway and HOXC6 might be a novel target in clinical
      treatment for gliomas.

PMID- 30228025
TI  - Detecting accidental punctures and lacerations during cholecystectomy in large
      datasets: Two methods of analysis.
AB  - BACKGROUND: After the Institute of Medicine (IOM) report To Err Is Human
      highlighted the impact of medical errors, the Agency for Healthcare Research and
      Quality (AHRQ) developed Patient-Safety Indicators (PSI) to improve quality by
      identifying potential inpatient safety problems. PSI-15 was created to study
      accidental punctures and lacerations (APL), but PSI-15 may underestimate APLs in
      populations of patients. This study compares PSI-15 with a more inclusive
      approach using a novel composite of secondary diagnostic and procedural codes.
      METHODS: We used Nationwide Inpatient Sample (NIS) data (2000-2012) from AHRQ's
      Healthcare Cost and Utilization Project (H-CUP). We analyzed PSI-15-positive and 
      negative cholecystectomies. Cross tabulations identified codes that were
      significantly more frequent among PSI-15-positive cases; these secondary
      diagnostic and procedural codes were selected as candidate members of a composite
      marker (CM) of APL. We chose cholecystectomy patients for study because this is
      one of the most common general operations, and the large size of NIS allows for
      meaningful analysis of infrequent occurrences such as APL rates. RESULTS: CM
      identified 1.13 times more APLs than did PSI-15. Patients with CM-detected APLs
      were significantly older and had worse mortality, comorbidities, lengths of stay,
      and charges than those detected with PSI-15. Further comparison of these two
      approaches revealed that time-series analysis for both APL markers revealed
      parallel trends, with inflections in 2007, and lowest APL rates in July.
      CONCLUSIONS: Although CM may yield more false positives, it appears more
      inclusive, identifying more clinically significant APLs, than PSI-15. Both
      measures presented similar trends over time, arguing against inflation in PSI-15
      reporting. While arguably less specific, CM may increase sensitivity for
      detecting APL events during cholecystectomies. These results may inform the
      interpretation of other large population studies of APLs following abdominal
      operations.

PMID- 30228026
TI  - Photic maculopathy: A review of the literature (I).
AB  - The human retina, as transducer of light energy, is especially exposed to light
      toxicity. Solar maculopathy has been the only form of photic maculopathy for
      millennia, often secondary to the observation of an eclipse. During the last
      century, technological advances have led to the appearance of new forms of photic
      maculopathy, related to the exposure to new forms of artificial light, such as
      welding devices and lasers. In recent years, the general use of laser pointers
      has led to an upturn in interest in this pathology. The aim of this review is to
      offer an integrated view of the different types of photic maculopathy. Due to the
      extension of this topic, the review is presented divided into two parts. In this
      first part solar maculopathy and welding arc maculopathy are presented.

PMID- 30228027
TI  - Cost-effectiveness Analysis of Regorafenib and TAS-102 in Refractory Metastatic
      Colorectal Cancer in the United States.
AB  - BACKGROUND: Regorafenib and TAS-102 are standard treatment options in refractory
      metastatic colorectal cancer based on improvement in overall survival by 6 and 8
      weeks, respectively, when compared with best supportive care alone (BSC). Given
      the small incremental clinical benefit, we evaluated their cost-effectiveness
      from a United States payer's perspective. MATERIALS AND METHODS: A Markov model
      was constructed to compare costs and effectiveness of regorafenib, TAS-102, and
      BSC. Model inputs for clinical efficacy and adverse events were from the CORRECT
      trial (Regorafenib monotherapy for previously treated metastatic colorectal
      cancer: an international, multicentre, randomised, placebo-controlled, phase 3
      trial) for regorafenib and the RECOURSE trial (Randomized, Double Blind, Phase 3
      Study of TAS-102 plus Best Supportive Care [BSC] versus Placebo plus BSC in
      Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapies)
      for TAS-102. The incremental cost-effectiveness ratios (ICERs) were reported to
      compare treatments. Model robustness was checked with univariate and
      probabilistic sensitivity analyses as well as a scenario analysis using the
      CONCUR trial data for regorafenib. RESULTS: In our base case, regorafenib and TAS
      102 had the ICERs of $395,223 per quality-adjusted life year (QALY) and $399,740
      per QALY versus BSC, respectively. Compared with regorafenib, TAS-102 provided an
      additional 0.041 QALY at the cost of $16,608 or $406,104 per QALY, but the
      differences were not robust in sensitivity analyses. The most influential
      parameters on the ICERs were efficacy and health state utility parameters as well
      as the cost of treating neutropenia. In probabilistic sensitivity analysis using
      cost-effectiveness acceptability curves, BSC was more cost-effective than both
      regorafenib and TAS-102 in 50% of repetitions at the willingness-to-pay threshold
      of $330,000 per QALY. CONCLUSION: Neither TAS-102 nor regorafenib are cost
      effective at standard willingness-to-pay thresholds (ie, $150,000 per QALY)
      relative to BSC. There is no clear evidence that either treatment has better
      relative value.

PMID- 30228028
TI  - Chronodisruption: An untimely cause of preterm birth?
AB  - Circadian rhythms, endogenous and entrainable adaptations to 24-hour cycles of
      light and dark, influence almost all physiologic functions. Emerging evidence
      suggests that the disruption of normal circadian rhythms, termed
      chronodisruption, could affect a wide range of disease-related processes. In this
      review, we describe the molecular generation of circadian rhythms, the effects of
      chronodisruption on human health, the circadian timing of birth in multiple
      species, the possible effects of chronodisruption on preterm birth, and some of
      the open questions in this field.

PMID- 30228029
TI  - Serum albumin nanoparticles vaccine provides protection against a lethal
      Pseudomonas aeruginosa challenge.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections
      in immunocompromised individuals and in patients with cystic fibrosis. A range of
      vaccines to prevent infections caused by P. aeruginosa has already been tested,
      yet no vaccine against this pathogen is currently available. The goal of this
      study was to evaluate the potential of bovine serum albumin nanoparticles (BSA
      NPs) associated with total P. aeruginosa ATCC 27853 antigens in inducing
      protection against the infection with virulent P. aeruginosa PA14 strain in
      murine model of nasal infection. Swiss mice were immunized with BSA-NPs
      associated with total P. aeruginosa antigens (NPPa) or empty NPs (NPe). As
      positive and negative control, groups of animals were immunized with total
      antigens of P. aeruginosa ATCC 27853 and phosphate buffered saline, respectively.
      Immunized mice were infected via nasal route using P. aeruginosa PA14 strain. The
      survival after 48 h was evaluated and the lungs from animals were processed for
      quantification of bacterial load, cytokine expression and histopathological
      analysis. After infection with P. aeruginosa PA14, animals immunized with NPPa
      had the highest survival rate, the lowest bacterial lung load, a controlled
      production of cytokines and few histopathological changes. These results indicate
      that NPPa immunization protected mice from infection, contributing for the
      elimination of the bacteria from the lungs, which consequently reflected the
      survival of the animals. Therefore, this vaccine was able to induce a functional
      response in an animal model of lethal infection and thereby is a promising
      platform for P. aeruginosa vaccines.

PMID- 30228030
TI  - Improving the stability of recombinant anthrax protective antigen vaccine.
AB  - Development of recombinant protective antigen (rPA)-based anthrax vaccines has
      been hindered by a lack of stability of the vaccines associated with spontaneous
      deamidation of asparagine (Asn) residues of the rPA antigen during storage. In
      this study, we explored the role that two deamidation-prone Asn residues located
      directly adjacent to the receptor binding site of PA, Asn713 and Asn719, play in
      the stability of rPA-based anthrax vaccines. We modified these residues to
      glutamine (Gln) and generated rPA(N713Q/N719Q), since Gln would not be expected
      to deamidate on a time scale relevant to vaccine storage. While wild-type rPA
      vaccine formulated with aluminum hydroxide lost immunogenicity upon storage, as
      measured by induction of toxin-neutralizing antibodies in mice, the
      rPA(N713Q/N719Q) vaccine did not exhibit a significant loss in immunogenicity.
      This finding suggests that modification of Asn713 and Asn719 of rPA to
      deamidation-resistant amino acids may improve the stability of rPA-based anthrax
      vaccines.

PMID- 30228031
TI  - Pediatric Provider Education and Use of Long-Acting Reversible Contraception in
      Adolescents.
AB  - INTRODUCTION: Pediatric primary care providers prescribe the majority of
      contraception to adolescents, but they often lack training in long-acting
      reversible contraception (LARC). Our objective was to assess whether a provider
      education initiative was associated with a change in LARC use for adolescents.
      METHOD: Using electronic medical records, we examined LARC use for 7,331 women
      ages 15 to 21years with an established primary care provider before and after a
      provider education initiative on LARC. We used an interrupted time series design
      to examine trends in LARC use related to the intervention. RESULTS: Before the
      intervention, 3.4% to 3.8% of adolescents were using a LARC method, and LARC use
      was declining by 4devices/10,000 adolescents per month (95% confidence interval =
      [-5, -2] per 10,000 adolescents). After the intervention, LARC use stabilized.
      The number of adolescents using a LARC method increased nonsignificantly at 3, 6,
      9, and 12 months after the intervention. DISCUSSION: Education of pediatric
      primary care providers reversed a trend toward decreased use of long-acting
      reversible contraception.

PMID- 30228032
TI  - Applying Human-Centered Design to the Development of an Asthma Essentials Kit for
      School-Aged Children and Their Parents.
AB  - This study aimed to design and test an asthma essentials kit to support parent
      child shared asthma management. Fourteen children (age range = 7-11 years) with
      asthma and their parents participated in this study. Development of the asthma
      essentials kit involved a generative phase, focused on understanding and
      designing to meet user needs, and an evaluative phase, which entailed narrowing,
      evaluating, and refining the asthma essentials kit. As is typical in human
      centered design, analysis was iterative throughout the design process such that
      findings informed each subsequent phase. The final asthma essentials kit concepts
      collectively addressed the three user-identified priorities: roles and
      responsibilities, desire for normalcy, and shared asthma management. Concept
      prototypes included a to-go bag, cue card, wearable device, and mobile health
      application. Usability and acceptability testing showed that the asthma
      essentials kit prototypes were highly useful, acceptable, and easy to navigate.
      Human-centered design holds promise in developing interventions to meet user
      needs.

PMID- 30228033
TI  - Development, Implementation, and Satisfaction With a Nurse Practitioner
      Professional Ladder: A Children's Hospital Experience.
AB  - This article describes the development and implementation of a nurse practitioner
      professional ladder (NPPL) at a large freestanding urban pediatric hospital. The
      NPPL was created to recognize advanced practice registered nurses and
      differentiate levels of clinical expertise, role development, leadership, and
      professional contributions into a three-tiered approach, designated as NP I, NP
      II, and NP III. The results of a nurse practitioner satisfaction survey at Year 2
      and Year 4 after the development of the NPPL are summarized. The NPPL helped
      create an empowering environment for continued nurse practitioner professional
      growth.

PMID- 30228034
TI  - Comparison of extrusion and patency of silicon versus thermoplastic elastomer
      tympanostomy tubes.
AB  - OBJECTIVES: This study aimed to assess the differences in the extrusion rate,
      patency and incidence of otorrhea according to the material properties of tubes
      in tympanostomy tube (TT) procedures. SUBJECTS AND METHODS: A total of 75
      children with bilateral chronic otitis media with effusion were randomized in
      this prospective trial to receive 1.02-mm-sized TTs (thermoplastic elastomer) in
      one ear and 1.14-mm-sized TTs (silicone) in the other ear. Data were obtained on
      ventilation tube type, time to extrusion, comorbidities, tube plugging, incidence
      of TT otorrhea during following up, and age of the patient. Postoperatively,
      follow-up by an otologist continued every two months to assess the incidence of
      otorrhea, plugging, and TT extrusion until all tubes were extruded. RESULTS: Out
      of the 75 children, 7 patients were excluded during surgery and 4 were lost
      during follow-up. The mean extrusion time of 1.02-mm-sized TTs (thermoplastic
      elastomer) was 10.28 months, whereas that of 1.14-mm-sized TTs (silicone) was
      7.36 months, which showed a significant difference. However, thermoplastic
      elastomer TTs had more plugging events than silicone TTs. CONCLUSIONS: There was
      a significant increase in the time to extrusion in ears with the 1.02-mm-sized
      thermoplastic elastomer TT, although, generally, the larger inner diameter of the
      tube last longer in the eardrum. This contrasting result is thought to be due to
      the different material properties of both TTs. This information may be helpful
      for TT selection in clinical practice depending on the patient's condition.

PMID- 30228035
TI  - Not all sedentary behaviour is equal: Children's adiposity and sedentary
      behaviour volumes, patterns and types.
AB  - OBJECTIVE: The importance of different constructs of sedentary behaviours in
      relation to childhood obesity is uncertain. Thus, this study aimed to investigate
      relationships between volume, patterns and types of sedentary behaviour and
      adiposity in children. METHODS: A case-control study was undertaken involving 234
      children aged 10-13years who were either of a healthy-weight (74 boys, 56 girls)
      or classified as obese (56 boys, 48 girls). Percent body fat (by dual-energy X
      ray absorptiometry) and waist-to-height ratio were assessed. Time, type
      (television, videogame, computer, eating, passive transport) and bout length of
      sedentary behaviours were measured using accelerometry and the Multimedia
      Activity Recall for Children and Adolescents. Time use (total daily energy
      expenditure, sleep, physical activity), age, household income and Tanner stage
      were covariates in sex-stratified partial least squares analyses. RESULTS: Daily
      energy expenditure and income were negatively associated with adiposity for both
      sexes. Television time was consistently positively associated with adiposity. In
      boys only, prolonged bouts of sedentary behaviour and time spent playing video
      games/computer were positively linked with adiposity. Non-screen sedentary
      behaviour was negatively associated with adiposity in girls. Independent of total
      energy expenditure, total sedentary time was only inconsistently associated with
      fatness. CONCLUSIONS: These data suggest that (1) characteristics of sedentary
      time other than duration are associated with adiposity in children, and (2)
      associations may be sex-specific.

PMID- 30228036
TI  - Four-Year Analysis of a Novel Milestone-Based Assessment of Faculty by General
      Surgical Residents.
AB  - OBJECTIVE: In response to our faculty's concerns about the quality and
      reliability of feedback from general surgery residents, we developed a novel
      faculty assessment tool. This study was designed as an interim analysis of the
      tool's effectiveness and discriminatory ability. METHODS: Our department's
      educational leadership developed milestones in 7 domains that were scored from 1
      to 4, with each level representing an educational approach that ranged from
      ineffective (1) to ideal (4). Each postgraduate year (PGY) class meets annually
      to develop a consensus regarding each faculty member's effectiveness in each of
      the 7 domains: (1) operative supervision, (2) operative teaching, (3) clinic
      and/or hospital supervision, (4) clinic and/or hospital teaching, (5) conference
      participation, (6) availability, and (7) overall contribution to the training
      program. We reviewed the results from the initial 4 years of this project. We
      also analyzed the annual national faculty survey administered by the
      Accreditation Council for Graduate Medical Education (ACGME) to evaluate faculty
      satisfaction regarding feedback during the same study period. Data were assessed
      using the Levene test for homogeneity, analysis of variance, and Wilcoxon-Mann
      Whitney tests. RESULTS: Forty-two faculty members were annually evaluated by 29
      to 32 residents. Each resident PGY class assigned faculty milestone scores that
      varied across the 7 domains, demonstrating that faculty scores reflected variable
      opinions about each specific domain, while avoiding labeling an effective faculty
      member with all high scores and a less effective member with all poor scores.(p <
      0.0001). Milestone scores for a given faculty member differed across PGY classes,
      indicating that junior residents might evaluate a specific faculty member
      differently than senior residents (p < 0.0001). Eleven faculty members received
      low scores of 1 or 2 on the overall contribution to training domain and 8/11
      (73%) improved to 3 or 4, the following year. Twenty core faculty members were
      included on the annual ACGME survey. The results from the study period on the
      ACGME anonymous faculty survey reflected enhanced satisfaction with resident
      feedback during the study period, improving from 68% to 88% compliance with ACGME
      standards and our mean program score improved from 4.1 to 4.4 compared to the
      national mean of 4.3 (p = 0.02). CONCLUSIONS: This milestone-based faculty
      assessment tool improves the quality of the feedback from surgical residents when
      evaluating faculty. When residents assign a negative statement to describe
      faculty educational effectiveness in a specific domain, performance improves. A
      milestone-based faculty assessment strategy should be explored on a national
      level.

PMID- 30228037
TI  - Academic training for advanced practice nurses: International perspective.
AB  - This article presents a general analysis about academic training of Advanced
      Practice Nurses at international level. Firstly, some essential and global
      characteristics of advanced practice training, the core competencies and the
      difficulties found in the implementation of the academic training programs for
      these figures are presented. Secondly, the reality of advanced practice training
      in our country is explained, with emphasis on some university programmes at
      Masters, level and the expansion of the official nursing specialties. Then the
      European situation is addressed, showing a great variability among countries in
      the implementation of these roles, as well as an important heterogeneity in the
      academic training associated with their performance. Lastly, continuing with the
      international perspective, the academic training for advanced practice nurses in
      the USA, Latin America, Africa, Asia and Oceania is described.

PMID- 30228038
TI  - Alpha-synuclein in erythrocyte membrane of patients with multiple system atrophy:
      A pilot study.
AB  - BACKGROUND: Multiple system atrophy(MSA) is a neurodegenerative disease
      characterized by intracellular alpha-synuclein deposits. There is an unmet need
      for blood-based biomarkers to diagnose MSA. Our previous studies have reported
      elevated alpha-synuclein levels in erythrocytes of MSA patients. However, alpha
      synuclein protein in the membrane and cytoplasm of erythrocytes in MSA have not
      been investigated. METHODS: The membrane and cytoplasm were extracted from
      erythrocytes in 77 patients with MSA and 133 healthy controls. Levels of total
      and oligomeric alpha-synuclein were detected using Electrochemiluminescence
      assays. The correlations between alpha-synuclein levels and clinical
      characteristics were explored in MSA group. The diagnostic value of erythrocyte
      alpha-synuclein for MSA was determined by Receiver operator characteristic curve.
      RESULTS: alpha-synuclein levels in the erythrocyte membrane were significantly
      elevated in MSA patients compared with the healthy controls (total alpha
      synuclein, p = 0.003; oligomeric alpha-synuclein/total alpha-synuclein, p =
      0.033; oligomeric alpha-synuclein/protein, p < 0.001). The combination of total
      and oligomeric alpha-synuclein levels in erythrocyte membrane could efficiently
      distinguish MSA from healthy controls (sensitivity of 79.2%; specificity of
      69.2%; area under the curve: 0.771). In contrast, no significant difference was
      found in erythrocyte cytoplasm alpha-synuclein levels. In the subgroup of 48
      patients with probable MSA, there was a weakly negative correlation between
      oligomeric alpha-synuclein/protein in erythrocyte membrane and disease duration
      (r = -0.336; p = 0.009). CONCLUSION: Our pilot study suggests that the membrane
      fraction of alpha-synuclein levels in erythrocyte were elevated in patients with
      MSA, and these levels may be decreased with the development of disease.

PMID- 30228039
TI  - Highly efficient deproteinization with an ammonifying bacteria Lysinibacillus
      fusiformis isolated from brewery spent diatomite.
AB  - To explore a new method for bio-regeneration of high-protein brewery spent
      diatomite, an ammonifying bacteria (BSD1) was screened out from it and identified
      as Lysinibacillus fusiformis. The protein degradation characteristics of BSD1 was
      studied with rice protein as the sole nitrogen source. Maximum protein
      degradation activity was obtained when BSD1 was inoculated with an inoculum of 5%
      into a medium with glucose as carbon source and initial pH value of 7.0 and
      incubated at 30 degrees C for 48 h. In this optimal condition, protein
      concentration decreased from 156.8 mg/L to 19.2 mg/L, and protein degradation
      efficiency of BSD1 reached 88%. Free amino acid analysis showed that the content
      of Phe, Tyr, Pro, Ala, Lys, Thr and His increased in protein degradation process.
      After degradation, NH4+N concentration producing in medium supernatant reached
      232.2 mg/L. These results indicated the strain BSD1 could transform proteins into
      free amino acids and eventually convert them to ammonium or ammonia. Furthermore,
      strain BSD1 could also be used for deproteinization of brewery spent diatomite
      and 51% of proteins in spent diatomite were degraded. After biological
      deproteinization the specific surface area and total pore volume of diatomite
      improved obviously. These results illustrated that the application of strain BSD1
      for bio-regeneration of high-protein brewery spent diatomite was efficient and
      feasible.

PMID- 30228040
TI  - Identification and analysis of binding residues in the CBM68 of pullulanase PulA
      from Anoxybacillus sp. LM18-11.
AB  - Carbohydrate binding module (CBM) as a kind of non-catalytic domain has
      significant effects on the substrate binding and catalytic properties of
      glycoside hydrolases. CBM68 of an Anoxybacillus sp. pullulanase (PulA) was
      identified as a new type of CBM in our previous studies. Then, four key substrate
      binding amino acid residues (Y14, V91, G92, and R96) were obtained by alanine
      substitutions in this work. Through kinetic analysis of the mutants, V91A and
      G92A showed significant reduction both in Km values and kcat values against
      pullulan. To further identify the changes of substrate affinities of V91A and
      G92A, devitalized mutants V91A-D413N and G92A-D413N were under measuring by
      surface plasmon resonance (SPR). Compared with that of PulA-D413N, the substrate
      affinities of V91A-D413N and G92A-D413N were improved by 1.6-fold and 2.2-fold,
      respectively. However, as to the product (maltotriose) binding force tested by
      the isothermal titration calorimetry (ITC), G92A showed higher binding force than
      that of V91A and PulA by 4.2-fold and 6.2-fold, respectively. That may cause G92A
      showing significantly lower catalytic efficiency than V91A and PulA. Moreover,
      four different kinds of amino acids (leucine, serine, glutamic acid and arginine)
      substitutions for V91 and G92 showed various changes both on the kinetic
      parameters and enzymatic properties, which demonstrated that V91 and G92 were the
      critical binding residues in the CBM68. The results of this study made
      contributed to the rational design for improving the catalytic efficiency of
      PulA.

PMID- 30228041
TI  - Structural and Functional Pulmonary Magnetic Resonance Imaging in Pediatrics-From
      the Neonate to the Young Adult.
AB  - The clinical imaging modalities available to investigate pediatric pulmonary
      conditions such as bronchopulmonary dysplasia, cystic fibrosis, and asthma are
      limited primarily to chest x-ray radiograph and computed tomography. As the
      challenges that historically limited the application of magnetic resonance
      imaging (MRI) to the lung have been overcome, its clinical potential has greatly
      expanded. In this review article, recent advances in pulmonary MRI including
      ultrashort echo time and hyperpolarized-gas MRI techniques are discussed with an
      emphasis on pediatric research and translational applications.

PMID- 30228042
TI  - Prevention of chronic pain: an acute pain management imperative.

PMID- 30228043
TI  - Bubble dynamics in boiling histotripsy.
AB  - Boiling histotripsy is a non-invasive, cavitation-based ultrasonic technique
      which uses a number of millisecond pulses to mechanically fractionate tissue.
      Though a number of studies have demonstrated the efficacy of boiling histotripsy
      for fractionation of solid tumours, treatment monitoring by cavitation
      measurement is not well studied because of the limited understanding of the
      dynamics of bubbles induced by boiling histotripsy. The main objectives of this
      work are to (a) extract qualitative and quantitative features of bubbles excited
      by shockwaves and (b) distinguish between the different types of cavitation
      activity for either a thermally or a mechanically induced lesion in the liver. A
      numerical bubble model based on the Gilmore equation accounting for heat and mass
      transfer (gas and water vapour) was developed to investigate the dynamics of a
      single bubble in tissue exposed to different High Intensity Focused Ultrasound
      fields as a function of temperature variation in the fluid. Furthermore, ex vivo
      liver experiments were performed with a passive cavitation detection system to
      obtain acoustic emissions. The numerical simulations showed that the asymmetry in
      a shockwave and water vapour transport are the key parameters which lead the
      bubble to undergo rectified growth at a boiling temperature of 100 degrees C. The
      onset of rectified radial bubble motion manifested itself as (a) an increase in
      the radiated pressure and (b) the sudden appearance of higher order multiple
      harmonics in the corresponding spectrogram. Examining the frequency spectra
      produced by the thermal ablation and the boiling histotripsy exposures, it was
      observed that higher order multiple harmonics as well as higher levels of
      broadband emissions occurred during the boiling histotripsy insonation. These
      unique features in the emitted acoustic signals were consistent with the
      experimental measurements. These features can, therefore, be used to monitor (a)
      the different types of acoustic cavitation activity for either a thermal ablation
      or a mechanical fractionation process and (b) the onset of the formation of a
      boiling bubble at the focus in the course of HIFU exposure.

PMID- 30228044
TI  - Surgery for Obesity and Related Diseases: I. A Novel Approach to the
      Quantification of the Longitudinal Speed of Sound and Its Potential for Tissue
      Characterization.
AB  - Described here is a method to determine the longitudinal speed of sound in
      speckle-dominated ultrasound images. The method is based on the concept that the
      quality of an ultrasound image is maximized when the beamformer's speed of sound
      matches the speed in the medium. The method captures the quality of the
      ultrasound image using two quantitative image-quality metrics: image brightness
      and sharpness around the intended focal zone. The proposed method requires no
      calibration, is computationally efficient and is deployable on commercial
      ultrasound systems without hardware or software modifications. Ex vivo testing on
      tissue-mimicking phantoms indicates the method's accuracy in predicting the true
      speed of sound to within 1% of ground truth values.

PMID- 30228045
TI  - Optimization of Phase-Change Contrast Agents for Targeting MDA-MB-231 Breast
      Cancer Cells.
AB  - Breast cancer remains a leading cause of death for women throughout the world.
      Recent advances in medical imaging technologies and tumor targeting agents
      signify vast potential for progress toward improved management of this global
      problem. Phase-change contrast agents (PCCAs) are dynamic imaging agents with
      practical applications in both the research and clinical settings. PCCAs possess
      characteristics that allow for cellular uptake where they can be converted from
      liquid-phase PCCAs to gaseous microbubbles via ultrasound energy. Previously, we
      reported successful internalization of folate-targeted PCCAs in MDA-MB-231 breast
      cancer cells followed by ultrasound-mediated activation to produce internalized
      microbubbles. This study examines the binding, internalization and activation of
      folate-receptor targeted PCCAs in MDA-MB-231 breast cancer cells as a function of
      gaseous core compositions, incubation time and ultrasound exposure period. In
      vitro results indicate that internalization and ultrasound-mediated activation of
      PCCAs were significantly greater using a 50:50 mixture of
      decafluorobutane:dodecafluoropentane compared with other core compositions: 50:50
      octafluoropropane:decafluorobutane (p < 0.0001), decafluorobutane (p < 0.04) and
      dodecafluoropentane (p < 0.0001). Furthermore, it was found that PCCAs composed
      of perfluorocarbons with higher boiling points responded with greater activation
      efficiency when exposed to 12 s of ultrasound exposure as opposed to 4 s of
      ultrasound exposure. When evaluating different incubation times, it was found
      that incubating the PCCAs with breast cancer cells for 60 min did not produce
      significantly greater internalization and activation compared with incubation for
      10 min; this was concluded after comparing the number of microbubbles present per
      cell before ultrasound versus post-ultrasound, and finding a ratio of
      intracellular microbubbles post-ultrasound/pre-ultrasound, 3.46 versus 3.14,
      respectively. The data collected in this study helps illustrate further
      optimization of folate-receptor targeted PCCAs for breast cancer targeting and
      imaging.

PMID- 30228046
TI  - Apheresis treatment of cryoglobulinemic vasculitis: A multicentre cohort study of
      159 patients.
AB  - OBJECTIVE: To assess the effectiveness of apheresis therapy (AT) in treating the
      clinical manifestations of patients with complicated cryoglobulinemic vasculitis
      (CV). METHODS: A retrospective cohort study of 159 CV patients attending 22
      Italian Centers who underwent at least one AT session between 2005 and 2015. The
      response to AT was evaluated on the basis of a defined grading system. RESULTS:
      Peripheral neuropathy was the most frequent clinical condition leading to AT.
      Therapeutic plasma exchange was used in 70.4% of cases. The outcome of AT was
      rated very good in 19 cases, good in 64, partial/transient in 40, and absent/not
      assessable in 36. Life-threatening CV-related emergencies and renal impairment
      independently correlated with failure to respond to AT. The independent variables
      associated with an increased risk of death were age at the time of the first AT
      session, multi-organ life-threatening CV, the presence of renal impairment and
      failure to respond to AT. The time-dependent probability of surviving until CV
      related death in the second year was 84%, with an AHR in patients with absent/not
      assessable response to AT of 11.25. CONCLUSION: In this study AT is confirmed to
      be a safe procedure in patients with CV. Early AT should be considered in
      patients with severe CV, especially in cases with impending renal involvement, in
      order to prevent irreversible kidney damage. Although its efficacy in patients
      with multi-organ failure is limited, AT is the only treatment that can rapidly
      remove circulating cryoglobulins, and should be considered an emergency
      treatment.

PMID- 30228047
TI  - DXA Measured Distal Femur Bone Mineral Density in Patients After Total Knee
      Arthroplasty: Method Development and Reproducibility.
AB  - INTRODUCTION: Total knee arthroplasty (TKA) is increasingly being performed.
      Distal femur periprosthetic fracture is a potentially catastrophic complication
      following TKA and existing data document substantial distal femur bone mineral
      density (BMD) loss following TKA. However, distal femur BMD is virtually never
      measured clinically as no consensus approach exists. This pilot study's purpose
      was to define regional BMD variation throughout the femur, suggest standard dual
      energy X-ray absorptiometry (DXA) regions of interest (ROIs) and evaluate BMD
      reproducibility at these ROIs. METHODS: Thirty volunteers 2-5 yr post TKA had
      both entire femurs imaged twice using a Lunar iDXA with subject repositioning
      between scans; the atypical femur fracture feature of enCORE software was
      utilized. To define femoral BMD distribution, custom 1cm ROIs were stacked one
      atop the other starting at the intercondylar notch and continuing to the base of
      the lesser trochanter. Femur length was measured with the ruler tool to calculate
      distance at 5% increments. ROIs encompassing each 5% increment were utilized to
      measure BMD at each location. Descriptive statistics were used to determine mean
      BMD at each ROI and reproducibility at the 15%, 25%, 45%, 60%, and 80% ROIs.
      RESULTS: The 5 and 10% ROIs included prosthetic and/or patella, causing high BMD
      values. Distal femur BMD was lowest at the 15% ROI and was higher (p < 0.05) at
      each more proximal ROI to 45%, then plateaued from 45% to 75%. BMD
      reproducibility at these regions was excellent; coefficient of variation (CV)
      from ~1% to 3.5%. As periprosthetic fractures generally occur in the distal
      femur, we propose measuring femur BMD using ROIs placed at 15% and 25%. A 60%
      region could also be used as a highly cortical site. CONCLUSION: Existing DXA
      capabilities allow distal femur BMD measurement with good reproducibility.
      Further research using standardized ROIs to assess distal femur BMD loss after
      TKA, and interventions to mitigate this loss, is indicated.

PMID- 30228048
TI  - Fibroblast Growth Factor 21 Is Associated With Bone Mineral Density, but not With
      Bone Turnover Markers and Fractures in Chinese Postmenopausal Women.
AB  - Fibroblast growth factor 21 (FGF21) is a member of the endocrine FGF subfamily
      and an important metabolic regulator that has multiple beneficial effects on
      glucose homeostasis and lipid metabolism. However, it was unclear whether FGF21
      would induce bone defects in humans. This study evaluated the associations of
      FGF21 levels, bone mineral density (BMD), osteoporotic fracture, and bone
      turnover marks (BTMs) in postmenopausal women. A total of 1342 postmenopausal
      Chinese Han women (511 cases of fragility fracture in the case group and 831
      cases in nonfragility fracture group) were enrolled. Serum FGF21 concentration
      was measured by ELISA (Quantikine), serum calcium (Ca), phosphate (P), alkaline
      phosphatase, 25-hydroxyvitamin D, parathyroid hormone, beta-crosslinked C
      telopeptide of type l collagen, were measured using an automated Roche electro
      chemiluminescence system. BMD was measured using dual-energy X-ray
      absorptiometry. The association with age, BMD, 25-hydroxyvitamin D, parathyroid
      hormone, beta-crosslinked C-telopeptide of type l collagen, and FGF21 levels were
      also evaluated in postmenopausal women. In nonfracture group and fragility
      fracture group, postmenopausal women's FGF21 level was 226.57pg/mL (149.11-354.43
      pg/mL) and 219.43pg/mL (147.21-323.74 pg/mL), respectively. There is no
      significant difference in serum FGF21 levels between the fragility fracture group
      and the nonfracture group (p = 0.160). There was a significant statistical
      difference in BMD between the fragility fracture group and the nonfracture group
      (p = 0.000). In multiple linear regression analysis, FGF21 levels were
      significantly positive associated with lumbar BMD in postmenopausal women (L1-4,
      p = 0.007), independent of other factors, especially in fragility fracture group
      (L1-4, p = 0.001). In addition, a significant positive association was also
      observed between serum FGF21 levels and age in postmenopausal women (p < 0.05).
      We reveal a positive correlation between serum FGF21 concentrations with lumbar
      BMD in Chinese Han postmenopausal women. No significant correlations are present
      between serum FGF21 and bone turnover marks or serum FGF21 and fragility fracture
      in our study.

PMID- 30228049
TI  - Prefrontal cortex rTMS reverses behavioral impairments and differentially
      activates c-Fos in a mouse model of post-traumatic stress disorder.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe mental illness
      correlated with alterations in fear extinction neurocircuits that involve
      prefrontal, amygdala and hippocampal structures. Current treatments indirectly
      restore prefrontal control of fear responses, but still cannot achieve full
      remission in all patients. OBJECTIVE/HYPOTHESIS: Repetitive TMS (rTMS) can
      directly and chronically act on subparts of the prefrontal cortex (PFC) as a
      potential alternative treatment. However, preclinical studies are needed to
      further the comprehension of its mechanisms and thus enhance its efficacy.
      METHODS: A 40-mm coil is used on a stereotaxic frame to apply 12-Hz high
      intensity rTMS of the ventromedial PFC (vmPFC) in a foot-shock mouse model of
      PTSD. Chronic rTMS treatment was applied 7 days after the shocks every day up to
      day 12 (5 sessions, 3750 pulses). RESULTS: One session of rTMS (750 pulses) was
      able to precisely evoke immediate c-Fos activity in an area of the vmPFC (0.5
      mm2) in preliminary control mice. When used in the foot-shock model, chronic rTMS
      treatment (n = 19) counteracted short-term episodic memory deficits at day 18,
      and enhanced extinction dynamics when reexposed to the shocking chamber at day
      22. Associated c-Fos activity was found increased in the rodent's vmPFC
      (infralimbic cortex), the basolateral amygdala and the ventral CA1 (hippocampal
      output). CONCLUSIONS: This study is the first to use prefrontal cortex rTMS in a
      mouse model of PTSD. Chronic rTMS of the vmPFC reversed stress-induced behavioral
      impairments and acted on distributed networks of fear extinction up to 10 days
      after treatment.

PMID- 30228050
TI  - Impact and outcomes of patients with congestive heart failure complicating non-ST
      segment elevation myocardial infarction, results from a nationally-representative
      United States cohort.
AB  - INTRODUCTION: Congestive heart failure (CHF) is seen in up to 13-25% of patients
      with NSTEMI. Recent data describing the impact of congestive heart failure (CHF)
      on in-hospital outcomes in patients with non-ST-segment elevation myocardial
      infarction (NSTEMI) in the United States is limited. We sought to examine the in
      hospital outcomes, and management of CHF in patients admitted to the hospital
      with NSTEMI. METHODS: National Inpatient Sample (NIS) database (2010-2014) was
      analyzed to identify patients with NSTEMI using ICD-9-CM codes. The primary
      outcome was in-hospital mortality. Propensity score-matching analysis compared
      mortality in CHF patients to matched controls without CHF. RESULTS: Of 247,624
      patients with NSTEMI, 84,115 (34%) had CHF. Patients with CHF were less likely to
      receive percutaneous coronary intervention (PCI) [20.48% vs. 40.9%, P < 0.001] or
      coronary artery bypass grafting (CABG) [8.2% vs 9.6%, P < 0.001] during
      hospitalization. Also, they had longer lengths of stay and higher risk for in
      hospital adverse outcomes. CHF was the strongest predictor of in-hospital death.
      The increased mortality risk was persistent after propensity matching (RR 1.27;
      95% CI 1.22 to 1.33). CONCLUSION: CHF among patients with NSTEMI is associated
      with increased risk for in-hospital mortality and adverse outcomes.

PMID- 30228052
TI  - Left Ventricular Decompression Using a Percutaneous Transvalvular Microaxial
      Ventricular Assist Device in Patients Receiving VA ECMO.

PMID- 30228051
TI  - Acute Kidney Injury After Cardiac Surgery: A Narrative Review of the Literature.
AB  - Acute kidney injury (AKI) is a common and serious complication of cardiac
      surgery. It is associated with increased morbidity and mortality. On a population
      level, the financial impact and overall incremental annual index hospitalization
      costs associated with AKI exceed $1 billion in the United States alone. The
      pathogenesis is multifaceted and complex. Although novel biomarkers may be useful
      in detecting AKI at an earlier stage, treatment of AKI remains elusive.
      Prevention of AKI is still key to the management of AKI, and strategies include
      maintenance of renal perfusion and avoidance of nephrotoxins and blood
      transfusion-related insults. Dialysis in severe AKI is established, but the
      optimal modality and dose remains an area of ongoing research.This narrative
      review assesses the pathophysiology of AKI, role of biomarkers, risk assessment,
      and management in cardiac surgical patients.

PMID- 30228054
TI  - To OTE or Not to OTE: That Is the Question-Current International Trends of on the
      Table Extubation After Pediatric Cardiac Surgery.

PMID- 30228053
TI  - Natriuretic Peptides in Cardiac Anesthesia and Intensive Care.
AB  - Natriuretic peptides, predominantly B-type, are widely used in cardiology as
      prognostic and diagnostic biomarkers or, much less often, as a substantive
      treatment tool. They are hormones that are produced mainly in the myocardium in
      response to overload and ischemia, and their level quite accurately reflects the
      degree of myocardial dysfunction. Although their use in cardiac anesthesia and
      intensive care setting seems to be very beneficial for assessing the risk of
      acute disturbance of myocardial function or its laboratory monitoring, the actual
      significance of natriuretic peptides in this area is not yet recognized. This is
      due to the lack of clear diagnostic and prognostic values for these biomarkers
      supported by high-quality researches. On the basis of the available data, main
      advantages, existing difficulties, and most effective ways of using natriuretic
      peptides for determining the risk of heart surgery and assessing the severity of
      sepsis, pneumonia, and other critical conditions have been discussed in this
      review. In addition, the expediency of using natriuretic peptides as target
      parameters for goal-oriented therapy and as a substantive tool for treatment is
      considered.

PMID- 30228055
TI  - Reflections on Aging and Wisdom.
AB  - The author experienced an unexpected finding over 30 years ago. Despite many
      losses, older primary care patients had less psychiatric symptomatology than
      younger patients. This has led to a long learning and teaching focus on the
      positive relationship between aging and wisdom. Some recent research challenges
      this relationship. To deal with this challenge the author reflects on two related
      but complex questions with which he has been struggling. Is there an adaptive
      value of aging? If wisdom is more likely with aging, why? He concludes that aging
      is culturally adaptive and that wisdom is aging's individual and societal
      adaptive strength.

PMID- 30228056
TI  - Role of ambient light in the detection of contrast elements in digital dental
      radiography.
AB  - OBJECTIVE: This study aimed to evaluate the effect of different ambient light
      levels on observer detection of small contrast differences in a contrast phantom
      by using a high-end liquid crystal display (LCD) monitor. STUDY DESIGN: An
      aluminum step wedge was converted into a contrast phantom by the addition of bore
      holes. Radiographic images of the contrast elements were presented to 20
      observers. Images were displayed in random order under different ambient light
      levels (0, 50, 200, and 500 lux) twice, and the observers had to determine if
      contrast elements were visible. Sensitivity and specificity were determined to
      calculate areas under receiver operating characteristic curves and Friedmann's
      test was applied to evaluate the influence of the ambient light level on observer
      performance. RESULTS: Mean AZ values were moderate for each ambient light level
      at 0.715, 0.793, 0.764, and 0.722 for 0, 50, 200, and 500 lux, respectively. The
      influence of the ambient light level on observer performance was not
      statistically significant (P > .05). CONCLUSIONS: There was no significant
      influence of ambient light between 0 and 500 lux on observer ability to detect
      small contrast details displayed on a high-end LCD monitor.

PMID- 30228057
TI  - A sessile nodule in the dorsum of the tongue.

PMID- 30228058
TI  - Allergic reactions in oral and perioral diseases-what do allergy skin test
      results show?
AB  - OBJECTIVE: The aim of this study was to examine potential allergic reactions to
      different materials in oral and perioral diseases. STUDY DESIGN: The study
      included 230 consenting subjects in total-180 patients with oral and perioral
      diseases (30 patients each in the following groups: angioedema, oral lichenoid
      reactions [OLRs], burning mouth syndrome [BMS], gingivostomatitis, cheilitis, and
      perioral dermatitis) and 50 healthy controls. Comprehensive diagnostic workups
      were performed prior to patch testing with standard series allergens and with
      specific dental materials and skin prick testing (SPT) for food, preservatives
      and additives, and inhalants. RESULTS: Positive allergy test results were more
      common in patients with oral diseases than in controls, with significantly
      greater frequency of contact allergies in the cheilitis group (P = .048). The
      most common allergens in the majority patients were cobalt chloride (13.3% in BMS
      vs 10% in controls) and nickel sulfate (10% in gingivostomatitis and 6.7% in
      cheilitis vs 3.3% in controls), and preservatives (23.3% in angioedema and BMS).
      CONCLUSIONS: Allergy skin tests are reliable and justified for diagnosing
      allergies in cases of persistent or recurrent oral diseases. This is the only way
      to confirm allergies and is the basis for consequent allergen avoidance for the
      benefit of the patient.

PMID- 30228059
TI  - Significant HONO formation by the photolysis of nitrates in the presence of humic
      acids.
AB  - The generation of HONO and NO2 by the photolysis of nitrates in the presence of
      humic acids (HA) was measured under various conditions. The photolysis
      experiments of HA, KNO3 and KNO3/HA under simulated sunlight was carried out by a
      flow tube reactor at ambient temperature and pressure. HONO and NO2 were major
      products by the photolysis of KNO3. By contrast, the photolysis of HA and KNO3/HA
      mainly generated HONO. HA significantly enhanced the formation of HONO during the
      photolysis process of KNO3. With increasing the KNO3 mass, the HONO formation
      rate (RHONO) on KNO3/HA increased while the photolysis rate normalized by the
      KNO3 mass exhibited an opposite trend. RHONO on KNO3/HA linearly increased with
      irradiation intensity (88-262 W/m2) and relative humidity (7-70%), whereas it
      linearly decreased with the pH (pH = 2-12). In addition, the reaction paths of
      the HONO formation by the photolysis of nitrates in the presence of HA were
      proposed according to experimental results. Finally, atmospheric implications of
      the enhanced HONO formation by the photolysis of nitrates in the presence of HA
      were discussed.

PMID- 30228060
TI  - Legacy and alternative brominated flame retardants in outdoor dust and pine
      needles in mainland China: Spatial trends, dust-plant partitioning and human
      exposure.
AB  - Concentrations of 26 brominated flame retardants (BFRs), including 19
      polybrominated diphenyl ethers congeners (PBDEs), 3 isomers of
      hexabromocyclododecanes (HBCDs), and 4 alternative BFRs (alt-BFRs;
      hexabromobenzene, pentabromotoluene, 1,2-bis(2,4,6-tribromphenoxy)ethane, and
      decabromodiphenylethane) were determined in outdoor settled dust and pine needles
      collected across mainland China. BFRs were extensively found in the two matrices,
      with mean total concentrations at 4090 and 314 ng/g dry weight (dw), in dust and
      pine needles, respectively. The total BFRs concentrations in dust significantly
      varied among three mixed-land-use categories, with mean concentrations of 74.3,
      1284, and 25,525 ng/g dw in rural, urban, and point source areas, respectively.
      For PBDE congeners, dust samples contained predominantly BDE-209 (69.2% of the
      total BFRs), whereas lower brominated PBDEs such as BDE-28 (19.7%), -47 (11.0%),
      and -99 (12.2%) accounted for higher proportions in pine needles. Spatial
      distribution of BFRs showed distinct geographical signatures with the highest
      levels found in South Central China. Application of McLachlan's framework to our
      data suggested that the uptake of BFRs in pine needles was controlled primarily
      by kinetically limited gaseous deposition and by particle-bound deposition.
      Assessment on human exposure to BFRs through outdoor dust ingestion revealed a
      low risk for Chinese adults and toddlers.

PMID- 30228061
TI  - Genotoxicity by long-term exposure to the auxinic herbicides 2,4
      dichlorophenoxyacetic acid and dicamba on Cnesterodon decemmaculatus (Pisces:
      Poeciliidae).
AB  - Long-term genotoxic effects of two auxinic herbicide formulations, namely, the
      58.4% 2,4-dichlorophenoxyacetic acid (2,4-D)-based DMA(r) and the 57.7% dicamba
      (DIC)-based Banvel(r) were evaluated on Cnesterodon decemmaculatus. Primary DNA
      lesions were analyzed by the single-cell gel electrophoresis methodology. Two
      sublethal concentrations were tested for each herbicide corresponding to 2.5% and
      5% of the LC5096h values. Accordingly, fish were exposed to 25.2 and 50.4 mg/L or
      41 and 82 mg/L for 2,4-D and DIC, respectively. Fish were continuously exposed
      for 28 days with replacement of test solutions every 3 days. Genotoxicity was
      evaluated in ten individuals from each experimental point at the beginning of the
      exposure period (0 day) and at 7, 14, 21 and 28 days thereafter. Results
      demonstrated for first time that 2,4-D-based formulation DMA(r) induced primary
      DNA strand breaks after 7-28 days exposure on C. decemmaculatus regardless its
      concentration. On the other hand, DIC-based formulation Banvel(r) exerted its
      genotoxic effect after exposure during 7-14 days and 7 days of 2.5 and 5%
      LC5096h, respectively. The present study represents the first evidence of primary
      DNA lesions induced by two widely employed auxinic herbicides on C.
      decemmaculatus, namely 2,4-D and DIC, following long-term exposure.

PMID- 30228062
TI  - Delineation of 3D dose-time-toxicity in human pulmonary epithelial Beas-2B cells
      induced by decabromodiphenyl ether (BDE209).
AB  - Due to frequent detection in environment as well as in the human body, the
      adverse effects of decabromodiphenyl ether (BDE209) have been extensively studied
      in the past few years. However, information regarding the inhalation toxicity of
      BDE209 to humans is currently limited. In this study, the cytotoxicity, cell
      damage, and inflammation markers including IL-6, IL-8, and TNF-alpha in the Beas
      2B cell line induced by BDE209 were measured using a central composite design.
      Results showed that as BDE209 concentrations (5-65 MUg mL-1) and exposure time (6
      30 h) were increased, cell viability sharply decreased from 99.7% to 29.7% and
      LDH activity increased from 0.1% to 13.1%. Furthermore, expression of IL-6, IL-8
      and TNF-alpha transcripts were enhanced from 4.7 to 29.1 fold, 3.4-68.9 fold, and
      2.8-47.0 fold, respectively, and the concentration of IL-6 and IL-8 proteins
      increased from 5.4 to 16.7 pg mL-1 and 71.0-550.0 pg mL-1, respectively. Results
      indicate that BDE209 exposure can inhibit cell viability, increase LDH leakage,
      and upregulate the transcript (mRNA) and protein levels of inflammatory markers
      of IL-6 and IL-8 in Beas-2B cells. Moreover, these effects were both dose- and
      time-dependent, and dose and time had a synergistic effect - enhancing toxicity
      when in combination. Cell density affected both LDH activity and IL-8 release but
      had little effect on cell activity and IL-6 release in the Beas-2B cells. In
      contrast, TNF-alpha protein was not detected but its mRNA expression level was
      upregulated. This study will provide a reference for human health risk
      assessment, especially for the toxic damage that BDE209 exposure can elicit in
      the respiratory tract.

PMID- 30228063
TI  - Toxicity of copper oxide nanoparticles to Neotropical species Ceriodaphnia
      silvestrii and Hyphessobrycon eques.
AB  - The increase of production and consumption of copper oxide nanostructures in
      several areas contributes to their release into aquatic ecosystems. Toxic effects
      of copper oxide nanoparticles (CuO NPs), in particular, on tropical aquatic
      organisms are still unknown, representing a risk for biota. In this study, the
      effects of rod-shaped CuO NPs on the Neotropical species Ceriodaphnia silvestrii
      and Hyphessobrycon eques were investigated. We also compared the toxicity of CuO
      NPs and CuCl2 on these species to investigate the contribution of particles and
      cupper ions to the CuO NPs toxicity. Considering the low copper ions release from
      CuO NPs (<1%), our results revealed that the toxicity of CuO NPs to C. silvestrii
      and H. eques was mainly induced by the NPs. The 48 h EC50 for C. silvestrii was
      12.6 +/- 0.7 MUg Cu L-1 and for H. eques the 96 h LC50 was 211.4 +/- 57.5 MUg Cu
      L-1 of CuO NPs. There was significant decrease in reproduction, feeding
      inhibition and increase in reactive oxidative species (ROS) generation in C.
      silvestrii exposed to CuO NPs. In fish H. eques, sublethal exposure to CuO NPs
      caused an increase in ROS generation in gill cells and an increase in cells
      number that were in early apoptotic and necrotic stages. Our results showed that
      CuO NPs caused toxic effects to C. silvestrii and H. eques and ROS play an
      important role in the toxicity pathway observed. Data also indicated that C.
      silvestrii was among the most sensitive species for CuO NPs. Based on predicted
      environmental concentration in water bodies, CuO NPs pose potential ecological
      risks for C. silvestrii and H. eques and other tropical freshwater organisms.

PMID- 30228064
TI  - Mutual promotion of apoptosis and autophagy in prepubertal rat testes induced by
      joint exposure of bisphenol A and nonylphenol.
AB  - BPA and NP are both typical endocrine disruptors, the exposed populations are
      widespread, and the health risks mustn't be ignored. However, the interactions
      between them on spermatogenesis are rarely mentioned. And the underlying
      mechanism is unclear yet. In the present study, prepubertal SD rats were exposed
      to different low doses of BPA and NP separately or jointly for 4 weeks. The
      results indicate that the joint exposure induced excessive apoptosis and
      autophagy in the testes, as proved by a series of characteristics such as
      chromatin condensation and autophagosomes formation. Besides, endocrine disorders
      and oxidative stress were also caused by the exposure. Apoptosis was mediated by
      the mitochondrial apoptosis pathway, since the Bax and Caspase-3 gene expressions
      significantly increased with a prominent decrease of Bcl-2. While autophagy was
      caused by the inhibition of the Akt/mTOR pathway, as the expressions of the
      downstream genes Beclin-1, Atg5, Atg12 and the split of LC3 protein increased
      altogether. Worse yet, autophagy and apoptosis might reinforce each other and
      make the situation more severe in the joint group. What's more, remarkable
      histopathological changes such as spermatogenic epithelium atrophy, germ cell
      loss, and various ultrastructural modifications were strongly related to the
      apoptosis and autophagy. In aggregate, this study shows the enormous risk on male
      reproductive system brought by the interactions between BPA and NP. The findings
      provide a broader vision to understand the roles of apoptosis and autophagy
      induced by the joint exposure in the aggravation of spermatogenesis impairment,
      which could be a reference for the situation of complex EDCs exposure-induced
      male reproductive toxicity, and possibly inspire us to find new ideas for
      preventive and therapeutic treatments.

PMID- 30228065
TI  - Soil aggregate-associated distribution of DDTs and HCHs in farmland and bareland
      soils in the Danjiangkou Reservoir Area of China.
AB  - Soil organic matter (SOM) is the principal aggregating agent for soil aggregation
      and also the main adsorbent for organochlorine pesticides (OCPs) such as
      dichlorodiphenyltrichloroethane (DDT) and hexachlorocyclohexane (HCH), which may
      thereby affect OCP distribution in soils subjected to different land use types.
      However, the potential effects of land use on SOM and OCP distribution patterns
      in soil aggregates are not well understood. In this study, soils from farmlands
      and barelands in the Danjiangkou Reservoir area were analyzed to determine the
      influence of land use on OCP distribution and composition in different aggregate
      fractions (>3, 1-3, 0.25-1, and <0.25 mm). The results showed that the levels of
      ?DDTs ranged from 9.01 to 27.48 with a mean of 14.40 ng g-1, and ?HCHs ranged
      from 2.06 to 4.66 with a mean of 3.19 ng g-1 in farmland soils. In comparison,
      bareland soils were less contaminated, with total DDTs and HCHs fell in the range
      of 0.75-5.01 ng g-1 and not detected (n.d.)-1.40 ng g-1 respectively. In regard
      to the distribution patterns in soil aggregates, the residual levels of ?DDTs and
      ?HCHs tended to a certain degree to enrich in microaggregates (<0.25 mm) relative
      to bulk soils. A further analysis revealed that the enrichment of ?DDTs and ?HCHs
      in microaggregates were mainly attributed to the accumulation of p,p'-DDE and
      beta-HCH. Moreover, SOM was found also enriched in microaggregates. The
      enrichment of SOM was significantly and positively correlated with these of
      ?DDTs, ?HCHs, and the dominant metabolites (i.e., DDE and beta-HCH) in both land
      use types. Such results indicated that the variations in behavior of OCPs could
      be linked to the processes of soil aggregate turnover. These findings may help to
      enrich the theory of soil OCPs sequestration and establish targeted strategies to
      mitigate their health risks in the environment.

PMID- 30228066
TI  - Sublethal effects of oil-contaminated sediment to early life stages of the
      Eastern oyster, Crassostrea virginica.
AB  - The explosion of the Deepwater Horizon (DWH) oil drilling rig resulted in the
      release of crude oil into the Gulf of Mexico. This event coincided with the
      spawning season of the Eastern oyster, Crassostrea virginica. Although oil bound
      to sediments constitutes an important source of polycyclic aromatic hydrocarbon
      (PAH) exposure to benthic organisms, toxicity of sediment-associated DWH oil has
      not been investigated in any bivalve species. Here, we evaluated the sublethal
      effects of acute exposure of gametes, embryos and veliger larvae of the Eastern
      oyster to different concentrations of unfiltered elutriates of sediment
      contaminated with DWH oil. Our results suggest that gametes, embryos and veliger
      larvae are harmed by exposure to unfiltered elutriates of contaminated sediment.
      Effective concentrations for fertilization inhibition were 40.6 MUg tPAH50 L-1
      and 173.2 MUg tPAH50 L-1 for EC201h and EC501h values, respectively. Embryo
      exposure resulted in dose-dependent abnormalities (EC20 and EC50 values were 77.7
      MUg tPAH50 L-1 and 151 MUg tPAH50 L-1, respectively) and reduction in shell
      growth (EC2024h value of 1180 MUg tPAH50 L-1). Development and growth of veliger
      larvae were less sensitive to sediment-associated PAHs compared to embryos.
      Fertilization success and abnormality of larvae exposed as embryos were the most
      sensitive endpoints for assessing the toxicity of oil-contaminated sediment. Bulk
      of measured polycyclic aromatic hydrocarbons were sediment-bound and caused toxic
      effects at lower tPAH50 concentrations than high energy water accommodated
      fractions (HEWAF) preparations from the same DWH oil. This study suggests risk
      assessments would benefit from further study of suspended contaminated sediment.

PMID- 30228067
TI  - Toxicity of copper hydroxide nanoparticles, bulk copper hydroxide, and ionic
      copper to alfalfa plants: A spectroscopic and gene expression study.
AB  - Bulk Cu compounds such as Cu(OH)2 are extensively used as pesticides in
      agriculture. Recent investigations suggest that Cu-based nanomaterials can
      replace bulk materials reducing the environmental impacts of Cu. In this study,
      stress responses of alfalfa (Medicago sativa L.) seedlings to Cu(OH)2
      nanoparticle or compounds were evaluated. Seeds were immersed in
      suspension/solutions of a Cu(OH)2 nanoform, bulk Cu(OH)2, CuSO4, and Cu(NO3)2 at
      25 and 75 mg/L. Six days later, the germination, seedling growth, and the
      physiological and biochemical responses of sprouts were evaluated. All Cu
      treatments significantly reduced root elongation (average = 63%). The ionic
      compounds at 25 and 75 mg/L caused a reduction in all elements analyzed (Ca, K,
      Mg, P, Zn, and Mn), excepting for S, Fe and Mo. The bulk-Cu(OH)2 treatment
      reduced K (48%) and P (52%) at 75 mg/L, but increased Zn at 25 (18%) and 75 (21%)
      mg/L. The nano-Cu(OH)2 reduced K (46%) and P (48%) at 75 mg/L, and also P (37%)
      at 25 mg/L, compared with control. Confocal microscopy images showed that all Cu
      compounds, at 75 mg/L, significantly reduced nitric oxide, concurring with the
      reduction in root growth. Nano Cu(OH)2 at 25 mg/L upregulated the expression of
      the Cu/Zn superoxide dismutase gene (1.92-fold), while ionic treatments at 75
      mg/L upregulated (~10-fold) metallothionein (MT) transcripts. Results
      demonstrated that nano and bulk Cu(OH)2 compounds caused less physiological
      impairments in comparison to the ionic ones in alfalfa seedlings.

PMID- 30228068
TI  - Presence of organohalide-respiring bacteria in and around a permeable reactive
      barrier at a trichloroethylene-contaminated Superfund site.
AB  - Trichloroethylene (TCE) is one of the most common groundwater contaminants in the
      United States; however clean-up efforts are a challenge due to its physical and
      chemical properties. TCE and several of its degradation products were detected in
      the groundwater of the Beaver Dam Road Landfill site (Beltsville, MD) at
      concentrations above accepted maximum contaminant levels. A permeable reactive
      barrier (i.e., biowall) was installed to remediate the groundwater. Microbial
      infiltration and colonization of the biowall with native site bacteria was
      expected to occur. An array of molecular biological tools was applied to survey
      the microbial community for presence of organohalide-respiring microorganisms at
      the site. Microorganisms belonging to methanogens, acetogens, sulfate-reducing
      bacteria, and chlorinated aliphatic hydrocarbon-metabolizing bacteria were
      identified, thus making way for the application of the microbial populations in
      the biowall bioaugmentation efforts. In concomitant laboratory studies, molecular
      approaches were used to monitor continuously-fed column reactors containing
      saturated biowall material spiked with a commercially-available, Dehalococcoides
      containing culture (SDC-9), with or without zero-valent iron (ZVI) shavings. The
      column without ZVI had the highest abundance of Dehalococcoides spp. (2.7 * 106
      cells g-1 material, S.D. = 3.8 * 105 cells g-1 material), while the addition of
      ZVI did not affect the overall population. Although the addition of ZVI and
      biostimulation did change ratios of the Dehalococcoides strains, the results
      suggests that if ZVI would be applied as a biowall material amendment,
      biostimulation would not be required to maintain a Dehalococcoides population.
      These experimental results will be utilized in future remediation and/or biowall
      expansion plans to utilize the natural resources most effectively at the biowall
      site.

PMID- 30228069
TI  - Heavy metals in slag affect inorganic N dynamics and soil bacterial community
      structure and function.
AB  - Heavy metal contamination of soil in the vicinity of mining sites is a serious
      environmental problem around the world when mining residue (slag) is dispersed as
      dust. We conducted an incubation experiment to investigate the effect of a slag
      containing high levels of Pb and Zn (62.2 and 33.6 g kg-1 slag as PbO and ZnO,
      respectively, sampled from a site formerly used as a lead and zinc mine) on the
      nitrogen cycle when mixed with soil (0-0.048 g slag g-1 soil). The nitrogen cycle
      provides many life supporting-functions. To assess the quality of the soil in
      terms of the nitrogen cycle we focused on the dynamics of nitrate and ammonium,
      and bacterial community structure and functions within the soil. After two weeks
      of pre-incubation, 15N-labeled urea (500 mg N kg-1) was added to the soil.
      Changes in soil pH, the concentration and 15N ratio of nitrate (NO3--N) and
      ammonium, and bacterial relative abundance and community structure were measured.
      Results indicated that increasing the ratio of slag to soil had a stronger
      negative effect on nitrification than ammonification, as suggested by slower
      nitrate accumulation rates as the slag:soil ratio increased. In the treatment
      with the highest amount of slag, the concentration of NO3--N was 50% of that in
      the controls at the end of the incubation. Regarding the bacterial community,
      Firmicutes had a positive and Planctomycetes a negative correlation with
      increasing slag concentration. Bacterial community functional analysis showed the
      proportion of bacterial DNA sequences related to nitrogen metabolism was
      depressed with increasing slag, from 0.68 to 0.65. We concluded that the slag
      impacted the soil bacterial community structure, and consequently influenced
      nitrogen dynamics. This study could form the basis of further investigation into
      the resistance of the nitrogen cycle to contamination in relation to soil
      bacterial community.

PMID- 30228070
TI  - Rapidly probing the interaction between sulfamethazine antibiotics and fulvic
      acids.
AB  - Antibiotics residuals in the environments receive wide concerns due to the high
      risk of generating antibiotic resistance. Natural organic matters (NOM) existed
      in the environments are considered to have the capacity of binding with organic
      contaminants, consequently influencing their speciation and transformation in the
      natural environments. To assess the migration of antibiotics in the environments,
      it is crucial to understand the binding mechanisms between NOM and antibiotics,
      which is still unclear due to the limit of available research methods. In this
      study, the interaction between fulvic acids (FA), one of the main components of
      NOM, and sulfamethazine (SMZ) was characterized by nuclear magnetic resonance
      (NMR) combined with surface plasmon resonance (SPR) and isothermal titration
      calorimetry (ITC) technology. The parameters related to kinetics and
      thermodynamics of the interaction were determined, and the possible mechanisms
      driving the interaction were also proposed. In addition, density functional
      theory (DFT) was used to predict the binding mode between FA and SMZ to reveal
      the interaction mechanism. Results indicate that FA can effectively bound with
      SMZ to form a stable complex with a binding constant at the level of 103 L/mol.
      The kinetic parameters including association and dissociation constants were 29.4
      L/mol/s and 6.64 * 10-3 1/s, respectively. Hydrophobic interaction might play
      significant roles in the binding interaction with ancillary contribution of pi-pi
      conjunction arising from the aromatic rings stacking of FA and SMZ.

PMID- 30228071
TI  - Metabolic characteristics of normal weight central obesity phenotype polycystic
      ovary syndrome women: a large-scale national epidemiological survey.
AB  - RESEARCH QUESTION: The aim was to investigate the metabolic profiles of women
      with normal weight but central obesity in polycystic ovary syndrome (PCOS).
      DESIGN: In total, 727 women with PCOS from a large-scale epidemiological survey
      were included. Diagnosis of PCOS was based on Rotterdam criteria. Subjects were
      categorized into four subgroups: (i) normal weight non-central obesity (NWNCO):
      body mass index (BMI) <=18.5 kg/m2 to <25 kg/m2 and waist-to-hip ratio (WHR)
      <0.85; (ii) normal weight central obesity (NWCO): BMI <=18.5 kg/m2 to <25 kg/m2
      and WHR >=0.85; (iii) obese non-central obesity (ONCO): BMI >=25 kg/m2 and WHR
      <0.85; and (iv) obese central obesity (OCO): BMI >=25 kg/m2 and WHR >=0.85. BMI,
      WHR, blood pressure, glucose and lipid profiles were measured. RESULTS: NWCO
      subjects had significantly higher percentages of insulin resistance, high
      triglycerides and low high-density lipoprotein cholesterol (HDL-C) than NWNCO
      subjects (all P < 0.05), and similar percentages compared with ONCO subjects.
      Compared with the NWNCO group, the NWCO group had higher age-adjusted risks of
      insulin resistance, high triglycerides and low HDL-C (odds ratio [OR] = 3.83, 95%
      confidence interval [CI] = 2.23-6.58; OR = 1.66, 95% CI = 1.00-2.77, OR = 1.60,
      95% CI = 1.11-2.30, respectively). CONCLUSIONS: PCOS women with normal weight but
      central obesity had increased risks of insulin resistance and dyslipidaemia
      compared with normal weight PCOS women without central obesity, suggesting that
      combining BMI with measurement of central obesity may provide better adiposity
      related metabolic risk factor stratification in clinical practice than either
      method alone.

PMID- 30228072
TI  - pH stability of human preimplantation embryo culture media: effects of culture
      and batches.
AB  - RESEARCH QUESTION: How stable is the pH of human preimplantation embryo culture
      media during IVF culture and is there variation in pH between batches of culture
      media? DESIGN: To evaluate pH stability, three batches of three culture media
      were incubated in triplicate without embryos (sham culture) at CO2 levels
      recommended by the manufacturers (5% or 6%) for 4 days. To evaluate differences
      in pH between batches, the pH of three batches of five culture media was measured
      in triplicate during 1 day of sham culture. Linear mixed models were used for the
      analysis. RESULTS: An increase in pH during 4 days of culture was found in all
      three culture media, but the observed increased values were within the generally
      accepted range for clinical practice (pH 7.2-7.4). One medium was pH 7.1 in the
      first 2 days, but this was within the range provided by the manufacturer for that
      medium. Three out of five analysed media showed batch variation in pH that
      exceeded the generally accepted range for clinical practice. CONCLUSIONS: A
      relevant difference in pH was found between batches of human preimplantation
      embryo culture media. This suggests that the CO2 level of incubators may need to
      be adjusted for new batches of culture medium based on measured pH, to anticipate
      batch variability and safely accommodate limited pH increase over time. This
      study was unable to identify the cause of the differences in pH between batches,
      and further investigation on a larger number of batches and other media seems
      warranted.

PMID- 30228073
TI  - Prevalence and authenticity of de-novo segmental aneuploidy (>16 Mb) in human
      blastocysts as detected by next-generation sequencing.
AB  - RESEARCH QUESTION: What is the prevalence and authenticity of de-novo segmental
      aneuploidies (>16 Mb) detected by next-generation sequencing (NGS) in human
      preimplantation blastocysts? DESIGN: Between April 2013 and June 2016, 5735
      blastocysts from 1854 couples (average age 33.11 +/- 5.65 years) underwent
      preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR)
      or for aneuploidy (PGT-A) using NGS on trophectoderm (TE) biopsy samples. The
      prevalence of de-novo segmental aneuploidy was calculated from these results.
      Forty blastocysts with de-novo segmental aneuploidy detected by NGS, which had
      been donated for research, were warmed for further fluorescence in-situ
      hybridization (FISH) analysis to confirm their authenticity. RESULTS: The
      frequency of de-novo segmental aneuploidies in blastocysts was 10.13% (581/5735);
      the phenomenon was not related to maternal age and occurred on all chromosomes.
      Of the 40 donated blastocysts, 39 were successfully warmed and fixed for FISH
      analysis at the single-cell level. The de-novo segmental aneuploidies identified
      by NGS were confirmed by FISH in all 39 blastocysts. However, the de-novo
      segmental aneuploidies in these blastocysts were not all pure patterns, with
      66.67% (26/39) of blastocysts exhibiting mosaic patterns varying from 8.30% to
      92.86% of cells with de-novo segmental aneuploidy. The concordance rate between
      NGS and FISH in TE and inner cell mass (ICM) samples was 47.69% (31/65).
      CONCLUSIONS: De-novo segmental aneuploidy above 16 Mb occurred in blastocysts and
      could be detected by NGS, while some aneuploidies existed as mosaics in both TE
      and ICM.

PMID- 30228074
TI  - One-Stage treatment for maxillofacial asymmetry with orthognathic and contouring
      surgery using virtual surgical planning and 3D-printed surgical templates.
AB  - PURPOSE: Asymmetry is one of the most common maxillofacial deformities. One-stage
      treatment for maxillofacial asymmetry with orthognathic and contouring surgery
      has been rarely reported. This retrospective study aims to investigate the
      feasibility of simultaneous orthognathic and facial bone contouring surgery with
      the help of virtual surgical planning and 3D-printed navigation templates for
      facial asymmetry. PATIENTS AND METHODS: From January 2012 to December 2015, 51
      patients diagnosed with maxillofacial asymmetry received treatment of combined
      orthognathic and contouring surgery under the guidance of virtual surgical
      planning and 3D-printed templates. Photographs and measurements were taken before
      and after operation to evaluate the effectiveness of the treatment. RESULTS:
      Photographs and cephalometric analysis showed the asymmetry was effectively
      corrected. All patients were satisfied with the aesthetic results. CONCLUSION:
      This study suggested the clinical feasibility of simultaneous orthognathic and
      contouring surgery for the treatment of maxillofacial asymmetry. Virtual surgical
      planning and 3D-printed surgical templates enable the surgeons to plan and carry
      out the procedure more predictably and achieve satisfactory outcomes.

PMID- 30228075
TI  - Unmet needs of Italian physicians managing patients with inflammatory bowel
      disease.
AB  - BACKGROUND: Little is known about the unmet needs of physicians caring for
      patients with inflammatory bowel disease (IBD). AIMS: This study explored the
      practical difficulties and needs for professional updating of Italian IBD
      physicians. METHODS: A questionnaire was distributed to 600 physicians attending
      IG-IBD meetings. RESULTS: 280 physicians completed the questionnaire (46.7%). On
      a 5-point Likert scale (from 1, strongly disagree to 5, strongly agree), they
      identified the most problematic issues in managing IBD patients as increasing
      bureaucracy (3.9), lack of extra-gastroenterological IBD expertise (3.4), lack of
      diagnostic techniques (3.1) and budget limitations (2.9). The most lacking
      techniques, ranked from 1 (greatest need) to 9 (lowest need), were: anti-drug
      antibody and trough level assays (2.7), device-assisted enteroscopy (3.1),
      exploration under anaesthesia (3.2), MR enterography (3.2), and bowel
      ultrasonography (3.3). About professional updating, respondents indicated (on a 5
      point Likert scale) that helpful topics were practical medicine (4.3), managing
      difficult patients (4.1), and guidelines (4.0). The most desired modality for
      updating was residential courses on clinical practice (4.3). CONCLUSION: Several
      factors potentially limit the best management of IBD patients in Italy.
      Satisfying these unmet needs could improve care for IBD patients.

PMID- 30228076
TI  - Implementation of a Perioperative Venous Thromboembolism Prophylaxis Program for
      Patients Undergoing Radical Cystectomy on an Enhanced Recovery After Surgery
      Protocol.
AB  - BACKGROUND: Novel venous thromboembolism (VTE) prophylaxis programs, including
      postdischarge pharmacologic prophylaxis, have been associated with decreased VTE
      rates. Such practices have not been widely adopted in managing radical cystectomy
      (RC) patients. OBJECTIVE: To evaluate the effect of a perioperative VTE
      prophylaxis program on VTE rates after RC. DESIGN, SETTING, AND PARTICIPANTS:
      Single-institution, nonrandomized, pre- and post-intervention analysis of 319
      patients undergoing RC at Brigham and Women's Hospital between July 2011 and
      April 2017. Patient and outcome data were prospectively collected as part of the
      American College of Surgeons National Surgical Quality Improvement Program.
      INTERVENTION: Before June 2015, patients only received postoperative
      pharmacologic and mechanical VTE prophylaxis in the inpatient setting. Starting
      June 2015, a perioperative VTE prophylaxis program was implemented as part of an
      enhanced recovery after surgery (ERAS) protocol, including a 28-d course of
      postdischarge enoxaparin. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary
      outcome was 30-d postoperative VTE rate. Secondary outcomes were perioperative
      bleeding rates, 30-d complication, readmission, and mortality rates, and length
      of stay. Univariate analysis was performed comparing outcomes between pre- and
      post-intervention cohorts. RESULTS AND LIMITATIONS: Of the 319 patients who
      underwent RC, 210 (66%) were in the pre- and 109 (34%) in the post-intervention
      cohort. VTE rate was significantly lower in the post-intervention cohort (n=1,
      0.9% vs n=13, 6.2%; p=0.04). Rates of perioperative bleeding (35% vs 33%; p=0.80)
      and 30-d readmissions related to bleeding (1% vs 3.7%; p=0.19) did not differ
      significantly. Single-institution data limits generalizability, and patient
      compliance with postdischarge enoxaparin was unknown. CONCLUSIONS: Implementation
      of a perioperative VTE prophylaxis program as part of an ERAS protocol that
      includes extended postdischarge pharmacologic prophylaxis was associated with
      decreased rate of VTE events after RC. Perioperative bleeding and readmissions
      related to bleeding did not increase with this intervention. PATIENT SUMMARY:
      This study evaluated whether clotting complication rates after radical cystectomy
      (RC) for bladder cancer can be reduced by implementing a new postoperative care
      pathway. This pathway reduced rates of clotting complications without increasing
      bleeding rates and should be considered for all patients undergoing RC.

PMID- 30228077
TI  - Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical
      dengue in children from Colombian populations.
AB  - BACKGROUND: Etiologic studies provide evidence that IL-4R and IL-6R receptors may
      play important roles in the regulatory mechanisms of the development of clinical
      dengue, especially in children which is a segment of the population with high
      severe dengue risk. Moreover, the allele frequencies and genetic associations may
      be influenced by the populational genetic background. Therefore, we performed a
      case-control study to evaluate possible associations between SNPs in IL4R and
      IL6R genes and clinical dengue in children from two Colombian populations.
      METHODS: We genotyped the rs1805016 (IL4R) and rs8192284 (IL6R) by PCR-RFLP
      method, in 298 symptomatic children and 648 asymptomatic controls. Three
      individual genetic ancestral proportions (APs) (European, Amerindian, African)
      were inferred by genotyping 29 AIMs (Ancestry informative markers). The variables
      gender, APs, and the population of origin were used like confusion variables.
      RESULTS: We found IL4R-rs1805016 GG genotype and G-allele carriers and IL6R
      rs8192284 AA genotype associated with clinical dengue in the pooled and Huila
      samples. Nevertheless, we found no association of these polymorphisms in the
      sample of Antioquia. CONCLUSIONS: For the first time, we report SNPs in IL4R and
      IL6R genes associated with clinical dengue, which contributes to understanding
      the genetic susceptibility to dengue disease. Moreover, these results may be
      influenced by genetic background and must be evaluated through functional
      analysis.

PMID- 30228078
TI  - Impact of hypoxic and mesopic environments on visual acuity, contrast sensitivity
      and accommodation in subjects with LASIK surgery and aircrew candidate.
AB  - BACKGROUND: The safety of Laser-assisted in situ keratomileusis (LASIK) in
      aircrew was unclear, in addition, LASIK was not yet approved for aircrew of
      Taiwan Air Force. This study was aimed to evaluate visual performance in LASIK
      eyes in hypoxic and twilight environment. METHODS: 48 myopic eyes of 24 subjects
      enrolled in this study were divided into LASIK group and control group. Subjects
      were exposed in hypoxic (15% O2) and mesopic (3 cd/m2) environment. Visual
      performance was evaluated using the Early Treatment of Diabetic Retinopathy Study
      (ETDRS) visual chart, and Functional Acuity Contrast Test (FACT) before and after
      the expirement. Physiological parameters of all subjects were measured and
      recorded throughout the experiment. RESULTS: There was no significant difference
      of the two groups regarding their age, height, weight, and BMI. There is
      significant difference of preoperative spherical refractive error between the two
      groups. The results of physiological parameters were similar between two groups.
      Under normoxic conditions, there were no significant difference regarding distant
      vision in photopic and mesopic environments, so as for near vision. As a whole,
      the contrast sensitivity of the LASIK group were lowered than that of the control
      group about 35%, under whether normoxic or hypoxic conditions; photopic or
      mesopic circumstances. Under normoxic conditions, the measured accommodation of
      the LASIK group were 21% lowered than that of the control group and 31% lowered
      under hypoxic circumstances. CONCLUSION: There was no significant difference of
      visual acuity between the two groups regarding hypoxic and mesopic environment,
      but reduced contrast sensitivity was significant in LASIK group as compared to
      those of the control group. Accommodation was significantly lowered in LASIK
      group, compared with control group, in hypoxic environment. Whether postoperative
      visual performance after LASIK in aircrew during flying duty is safe might need
      further investigation.

PMID- 30228079
TI  - Signs of Dehydration in Nursing Home Residents.
AB  - OBJECTIVES: Although dehydration can affect mental and physical health, there is
      no clear, consistent, and reproducible diagnostic tool for this condition in
      older people. We applied multiple methods to detect dehydration with the aim of
      assessing the value of using urine analysis for this purpose. DESIGN:
      Nonrandomized cohort study. SETTING AND PARTICIPANTS: Sixty nursing home
      residents, aged 64-103 (mean 84) years. METHODS: Sampling of morning urine, blood
      analyses, and clinical examination. A previously validated algorithm summarized
      the urine specific gravity, osmolality, creatinine, and color to a Fluid
      Retention Index (FRI). RESULTS: The cut-off for renal fluid conservation
      consistent with dehydration (FRI >= 4.0) was reached by 51% of the cohort. No
      statistically significant linear correlation was found between FRI and serum
      osmolality (mean 307.5 mOsmol/kg) or plasma sodium (mean 139 mmol/L), but the
      subjects reported less thirst with increasing FRI scores (linear correlation r = 
      0.35; P < .03). Clinical examinations of mucous membranes and tongue furrows did
      not correlate with other markers of dehydration. Subjects with sunken eyes had
      higher C-reactive protein (P < .02) and lower albumin (P < .002) concentrations
      in plasma than the others, while impaired skin turgor only correlated with age (P
      < .04). CONCLUSIONS/IMPLICATIONS: Renal fluid conservation consistent with
      dehydration was found in half of the nursing home residents, which could
      partially be accounted for by decreased thirst. Clinical examinations probably
      reflected the physical status and age more than dehydration. The lack of
      correlation between the serum osmolality and the FRI, both of which are purported
      to be gold standards for dehydration, raises questions about whether a gold
      standard exists.

PMID- 30228080
TI  - Genetic structure analysis of Amblyomma mixtum populations in Veracruz State,
      Mexico.
AB  - Amblyomma mixtum Koch, 1844 parasitizes livestock, humans, and wildlife in
      Mexico. However, information on population genetics for this tick species in the
      country is missing. Tick samples were collected from livestock in ten regions
      across the state of Veracruz (22 degrees 28'N, 17 degrees 09'S, 93 degrees 36'E,
      98 degrees 39'W) to analyze the genetic structure of   A. mixtum populations.
      Ticks were morphologically identified using taxonomic keys. In order to test the
      intra-specific variability of A. mixtum fragments of the mitochondrial gene 16S
      rRNA and cytochrome oxidase subunit 1 (COI) were amplified. Ninety-six sequences
      were amplified from the 50 specimens' analyzed (96% amplification success).
      Eleven haplotypes were detected in 16S-rRNA gene and 10 more for COI. Neutrality
      tests showed negative results in most of the locations analyzed, which is
      indicative of an excess of recently derived haplotypes. However, these results
      were not statistically significant. Minimal union network analysis revealed that
      there is no separation of populations by geography, and that there is an overlap
      of several haplotypes among diverse populations. Significant genetic
      differentiation was not detected in the A. mixtum populations sampled in the
      state of Veracruz, Mexico, this may be due to the frequent movement of livestock
      hosts. This is the first report on the genetic structure of A. mixtum populations
      in Mexico.

PMID- 30228081
TI  - Comment on: histologic improvement of NAFLD in patients with obesity after
      bariatric surgery based on standardized NAS (NAFLD activity score).

PMID- 30228082
TI  - The effect of omentectomy added to bariatric surgery on metabolic outcomes: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Excess visceral adipose tissue has been identified as an important
      risk factor for obesity-related co-morbidities. Conflicting information exists on
      whether omentectomy added to bariatric surgery is beneficial to metabolic
      variables. OBJECTIVE: To evaluate the impact of omentectomy added to bariatric
      surgery on metabolic outcomes SETTING: University Hospital, Canada. METHODS:
      MEDLINE, EMBASE, and PubMed were searched up to May 2018. Studies were eligible
      for inclusion if they were randomized controlled trials comparing omentectomy
      added to bariatric surgery with bariatric surgery alone. Primary outcome measures
      were absolute change in metabolic variables (body mass index, insulin, glucose,
      cholesterol, lipoproteins, and triglycerides); secondary outcomes were changes in
      adipocytokines. Pooled mean differences (mean deviation; MD) were calculated
      using random effects meta-analyses, and heterogeneity was quantified using the I2
      statistic. RESULTS: Ten trials involving a total of 366 patients met the
      inclusion criteria with a median follow-up time of 1 year after surgery. Adding
      omentectomy to bariatric surgery demonstrated a minimal but statistically
      significant decrease in body mass index compared with bariatric surgery alone (MD
      1.29, 95% confidence interval .35-2.23, P = .007, I2 = 0%, 10 trials).
      Conversely, patients who underwent bariatric surgery alone had significant
      increases in high-density lipoprotein (MD -2.12, 95% confidence interval -4.13 to
      -.11, P = .04, I2 = 0%, 6 trials). Other metabolic outcomes and adipocytokines
      showed no significant difference between procedures. CONCLUSION: The addition of
      omentectomy to bariatric surgery results in minimal reduction of body mass index.
      Considering no overall improvement in metabolic outcomes and the time and effort
      required, the therapeutic use of omentectomy added to bariatric surgery is not
      warranted.

PMID- 30228083
TI  - Plication for Severe Peyronie's Deformities Has Similar Long-Term Outcomes to
      Milder Cases.
AB  - INTRODUCTION: Penile plication (PP) for Peyronie's disease (PD) is an established
      treatment option for mild to moderate curvature, but scant data exist regarding
      its utility in severe deformities. AIM: To evaluate long-term outcomes among men
      undergoing PP for PD, comparing severe to mild/moderate penile deformities.
      METHODS: We performed a retrospective review of patients who underwent PP for PD
      between 2009 and 2017. All patients underwent multiple parallel tunical plication
      without degloving. Severe PD was defined as either curvature >=60 degrees or
      biplanar curvature >=35 degrees. Patient demographics and surgical outcomes were
      analyzed. A modified PD Questionnaire and International Index of Erectile
      Function (IIEF)-5 were administered by telephone. MAIN OUTCOME MEASURE: Long-term
      patient-reported outcomes were evaluated from a modified survey incorporating the
      PD Questionnaire and IIEF-5. RESULTS: Of 327 PP patients, 102 (31%) responded to
      the telephone survey at a median 59.5 months (interquartile range 28.3-84) since
      surgery. Patients were equally distributed into severe (n = 51) and mild/moderate
      (n = 51) groups. Despite a greater mean degree of curvature in severe compared to
      mild/moderate patients (71.6 degrees vs 37.7 degrees, respectively, P < .001),
      correction of penile curvature was achieved in 91% of patients, with a mean
      change of 60.7 degrees in severe cases compared to 31.4 degrees in mild/moderate
      cases (P < .001). Equal numbers of patients in severe and mild/moderate groups
      reported improvement of penile curvature (74.5% vs 74.5%, P = 1.0) and sexual
      function (51.0% vs 49.0%, P = .84). PD Questionnaire metrics were likewise
      similar between severe and mild/moderate patients (P > .1), as were rates of
      subjective penile shortening (62.7% vs 62.7%, P = 1.0) and IIEF-5, both pre
      operatively (19.5 vs 19.7, P = .9) and post-operatively (19.4 vs 17.6,
      respectively, P = .15). On multivariate logistic regression, worsening sexual
      function was significantly associated with increased age (odds ratio 1.07, P =
      .01) and pre-operative IIEF (odds ratio 1.14, P = .02). CLINICAL IMPLICATIONS: PP
      should be considered in PD patients with severe deformities, as outcomes are
      favorable and comparable to those with milder curvature. STRENGTH & LIMITATIONS:
      This is a novel study evaluating long-term patient-reported outcomes after PP,
      comparing patients with severe deformity to those with mild/moderate curvature.
      The study was limited by retrospective design, relatively low survey response
      rate (31%), and lack of validated post-operative PD questionnaire. CONCLUSION:
      Long-term patient-reported outcomes of PP for severe PD deformities are
      comparable to mild/moderate cases, supporting broader application of PP beyond
      milder deformities. Reddy RS, McKibben MJ, Fuchs JS, et al. Plication for Severe
      Peyronie's Deformities Has Similar Long-Term Outcomes to Milder Cases. J Sex Med
      2018;15:1498-1505.

PMID- 30228084
TI  - Targeting BER enzymes in cancer therapy.
AB  - Base excision repair (BER) repairs mutagenic or genotoxic DNA base lesions,
      thought to be important for both the etiology and treatment of cancer. Cancer
      phenotypic stress induces oxidative lesions, and deamination products are
      responsible for one of the most prevalent mutational signatures in cancer.
      Chemotherapeutic agents induce genotoxic DNA base damage that are substrates for
      BER, while synthetic lethal approaches targeting BER-related factors are making
      their way into the clinic. Thus, there are three strategies by which BER is
      envisioned to be relevant in cancer chemotherapy: (i) to maintain cellular growth
      in the presence of endogenous DNA damage in stressed cancer cells, (ii) to
      maintain viability after exogenous DNA damage is introduced by therapeutic
      intervention, or (iii) to confer synthetic lethality in cancer cells that have
      lost one or more additional DNA repair pathways. Here, we discuss the potential
      treatment strategies, and briefly summarize the progress that has been made in
      developing inhibitors to core BER-proteins and related factors.

PMID- 30228085
TI  - Pre-transplant weight loss and clinical outcomes after lung transplantation.
AB  - BACKGROUND: Patients with greater adiposity before lung transplantation are at an
      increased risk for worse post-transplant outcomes. Few studies have addressed
      whether pre-transplant weight loss mitigates this risk. In this study we examined
      the association between pre-transplant weight loss and post-transplant clinical
      outcomes. METHODS: We conducted a retrospective cohort study of patients who
      received a lung transplant at the Duke University Hospital from May 1, 2005 to
      April 30, 2015. The sample included adult transplant recipients with restrictive,
      obstructive, and vascular diseases. Cox proportional hazards models were used to
      examine mortality and chronic lung allograft dysfunction (CLAD)-free survival,
      and negative binomial regression analyses were used to examine length of stay
      (LOS). Weight loss was assessed from change in body mass index (BMI). RESULTS:
      The cohort consisted of 810 patients. Initially, 403 (50%) were overweight and
      109 (13%) were obese by BMI criteria. Greater pre-transplant weight loss was
      associated with dose-response improvements in survival (hazard ratio [HR] 0.83
      [0.72 to 0.97], p = 0.018), with modest (0% to 3%, HR 0.91), moderate (7% to 10%,
      HR 0.83), and high (>15%, HR 0.71) levels of weight loss conferring longer
      survival, independent of initial weight (p = 0.533 for interaction). Weight loss
      was also associated with improved CLAD-free survival (HR 0.84 [0.71 to 0.99], p =
      0.034) and shorter LOS (b = -0.17, p < 0.001). CONCLUSIONS: Weight loss before
      transplantation was associated with improved short- and long-term clinical
      outcomes, independent of initial weight. Survival improved proportionally to
      percentage of weight lost. The mechanisms by which weight loss improve clinical
      outcomes warrant further exploration.

PMID- 30228087
TI  - Conventional MRI combined with DTI for neonatal hyperbilirubinemia;
      Methodological issues on diagnostic value.

PMID- 30228086
TI  - Electrical power to run ventricular assist devices using the Free-range Resonant
      Electrical Energy Delivery system.
AB  - BACKGROUND: Models of power delivery within an intact organism have been limited
      to ionizing radiation and, to some extent, sound and magnetic waves for
      diagnostic purposes. Traditional electrical power delivery within the intact
      human body relies on implanted batteries that limit the amount and duration of
      delivered power. The efficiency of current battery technology limits the
      substantial demands required, such as continuous operation of an implantable
      artificial heart pump within a human body. METHODS: The fully implantable,
      miniaturized, Free-range Resonant Electrical Energy Delivery (FREE-D) system,
      compatible with any type of ventricular assist device (VAD), has been tested in a
      swine model (HVAD) for up to 3 hours. Key features of the system, the use of high
      quality factor (Q) resonators together with an automatic tuning scheme, were
      tested over an extended operating range. Temperature changes of implanted
      components were measured to address safety and regulatory concerns of the FREE-D
      system in terms of specific absorption rate (SAR). RESULTS: Dynamic power
      delivery using the adaptive tuning technique kept the system operating at maximum
      efficiency, dramatically increasing the wireless power transfer within a 1-meter
      diameter. Temperature rise in the FREE-D system never exceeded the maximum
      allowable temperature deviation of 2 degrees C (but remained below body
      temperature) for an implanted device within the trunk of the body at 10 cm (25%
      efficiency) and 50 cm (20% efficiency), with no failure episodes. CONCLUSIONS:
      The large operating range of FREE-D system extends the use of VAD for nearly all
      patients without being affected by the depth of the implanted pump. Our in-vivo
      results with the FREE-D system may offer a new perspective on quality of life for
      patients supported by implanted device.

PMID- 30228088
TI  - Prophylaxis of Infective Endocarditis in Dentistry: Analysis of the Situation
      After Almost a Decade of Clinical Practice Guidelines.

PMID- 30228089
TI  - The incidence rate, trend and microbiological aetiology of prosthetic joint
      infection after total knee arthroplasty: A 13 years' experience from a tertiary
      medical center in Taiwan.
AB  - BACKGROUND/PURPOSE: Total knee arthroplasty (TKA) improves the patient's quality
      of life by relieving pain, correcting the deformity, and helping the patient
      resume normal activities. However, post-TKA prosthetic joint infection leads to
      implant failure, is difficult to treat, and causes a significant burden both
      economically and health-wise. Therefore, an understanding of the current trends
      in this infection and microbiology data is essential for preventing and treating
      it. METHODS: A retrospective study was conducted on 10,768 patients who underwent
      primary TKA at Taipei Veterans General Hospital, Taiwan, from 2002 to 2014. The
      incidence of post-TKA prosthetic joint infection in different time periods was
      investigated, and microbiological results in early- (<3 months post-TKA) and
      delay-onset prosthetic joint infection were analyzed. RESULTS: The 2 years
      incidence of post-TKA prosthetic joint infection was 1.93% (2002-2006), 1.05%
      (2007-2010), and 0.76% (2011-2014). The incidence of post-TKA prosthetic joint
      infection decreased significantly from 2002 to 2014. Although Staphylococcus
      species was most commonly isolated, a significantly higher proportion of gram
      negative bacteria were isolated from early-onset compared with delay-onset post
      TKA prosthetic joint infection patients: 9/29 (31.0%) versus 13/100 (13%); p =
      0.023. CONCLUSIONS: The results showed that the risk of post-TKA prosthetic joint
      infection is decreasing. Microbiology results showed that early-onset post-TKA
      prosthetic joint infection is associated with a higher risk of gram-negative
      bacterial infection. Physicians should be aware of this risk in order to
      correctly select empirical agents.

PMID- 30228090
TI  - The Effect of Progressive Muscle Relaxation on Emotional Competence: Depression
      Anxiety-Stress, Sense of Coherence, Health-Related Quality of Life, and Well
      Being of Unemployed People in Greece: An Intervention Study.
AB  - OBJECTIVES: Assessment of the impact of Jacobson Progressive Muscle Relaxation
      (PMR) on depression-anxiety-stress symptoms, sense of coherence, health-related
      quality of life and well-being in long-term unemployed people with anxiety
      disorders. DESIGN AND SETTING: An intervention study was conducted at a relevant
      Organization, in Athens, Greece. INTERVENTION: 50 long-term unemployed
      individuals suffering from anxiety disorders participated in the study.
      Participants were separated into two groups: (a) the intervention group (30
      individuals) that was trained on an 8-week on Progressive Muscle Relaxation
      program and also received counseling services and (b) the control group (20
      individuals) that received only counseling services. MAIN OUTCOME MEASURES:
      Depression, Anxiety, Stress Scale, Sense of Coherence, Health-Related Quality of
      Life and Well-being were evaluated at baseline and after the intervention.
      RESULTS: Significant changes were noted in the studied variables between the two
      groups, with improved outcomes in the intervention group. The intervention group
      showed a decrease in the symptoms of depression, anxiety, stress (p < 0.001)
      [depression (p < 0.001), anxiety (p < 0.001), stress (p < 0.001)], a higher score
      of sense of coherence (p < 0.001), improved health-related quality of life
      regarding the mental health domain (p < 0.001), and improvement in well-being (p
      < 0.001). No significant change was observed in the control group during the
      follow-up period.

PMID- 30228091
TI  - Urinary continence appears to enhance social participation and intimate relations
      in adolescents with myelomeningocele.
AB  - INTRODUCTION: The majority of adults with myelomeningocele (MMC) in Western
      Sweden use incontinence pads. There is an ongoing discussion as to whether
      continence improves the quality of life (QoL) in individuals with MMC as it has
      been hard to establish that an increase in QoL measured by generic health-related
      quality of life (HRQoL) instruments is achieved by continence surgery. OBJECTIVE:
      The hypotheses are that patients who are actively involved in a
      urotherapy/urology program are more continent than patients who are not and that
      urinary continence is one of the conditions required to enable social
      participation and physical intimacy. STUDY DESIGN: All 25 individuals in Western
      Sweden with MMC (15 males) aged 16-18 years were involved in this cross
      sectional, prospectively designed study of urinary and fecal continence. During
      interviews, questions were asked about the following: clean intermittent
      catheterization (CIC) and bowel regimens, the need for reminders or help from an
      assistant, social participation, and physical intimacy with a partner. RESULTS:
      In the group, overall 17 of 25 (68%) had achieved urinary continence, 19 of 25
      (76%) had a medical history of fecal continence, and 14 of 25 (56%) had no
      prescription for incontinence pads. Those who were urinary continent (17)
      included all nine patients who had received continence surgery in addition to six
      patients taking anticholinergics and two following the CIC procedure only.
      Urinary incontinence due to sphincter insufficiency was found in eight
      individuals, all of whom declined surgical treatment. All individuals (25/25)
      physically catheterized themselves, and 15/25 (60%) performed the fecal
      elimination regimen independently. Twelve individuals participated actively in
      social life, and eight of them had, or had had, a partner. All these 12 were
      urinary continent, and all but one were able to follow a fecal elimination
      regimen independently. Three of the 12 said they were fecal incontinent but knew
      how to become continent by following the prescribed fecal elimination regimen.
      DISCUSSION: Studies in this patient group have shown that incontinence means that
      it's harder to live a healthy adult life. Children too worry about incontinence
      episodes at school, and 70% consider urinary incontinence a problem. A limitation
      in the study is the small population, something often seen in rare diseases.
      CONCLUSIONS: With standardized follow-up, active treatment strategy and uro/bowel
      therapy, the urinary continence rate in adolescents with MMC at the study center
      is high compared with adults with MMC in Sweden. It appears that urinary
      continence is important in enabling successful participation in social life and
      in intimate physical relations with others.

PMID- 30228092
TI  - Early transplantation into a vesicostomy: a safe approach for managing patients
      with severe obstructive lesions who are not candidates for bladder augmentation.
AB  - INTRODUCTION: Management of severe antenatally detected oligohydramnios with and
      without obstruction is improving with the result that more fetuses are surviving
      with early renal failure. Significant advances have occurred in all specialties
      involved in the management of these patients. All these specialties working
      together have resulted in the survival of more patients born with renal failure.
      OBJECTIVE: The aim of this study is to highlight the medical advances in
      antenatal management of fetal oligohydramnios and pulmonary hypoplasia and to
      demonstrate that transplantation into a diverted urinary system is safe and leads
      to good outcomes. STUDY DESIGN: A case series of five patients were presented
      who, at the study center's respective facilities, recently underwent renal
      transplantation into bladders drained by cutaneous vesicostomy after extensive
      bladder evaluation and whose clinical cases highlight the aim of this study.
      RESULTS: A total of 5 patients were reviewed. Renal failure was caused by
      posterior urethral valves in four patients, and in one patient Eagle-Barrett
      syndrome. One patient received an amnio-infusion and attempted antenatal bladder
      shunt. One patient was ventilator dependent until 24 months, and required a
      tracheostomy, while two patients were ventilator dependent for the first few
      months of life. Three of five patients were dialysis dependent. Patient age at
      transplantation ranged from 20 to 61 months. All patients were poorly compliant
      pre-transplant and had bladder capacities ranging from 10 mL to 72 mL. Months
      since follow-up ranged from 3 to 64 months. Creatinine levels prior to transplant
      ranged from 1.9 to 5.6. During the follow up period, this range decreased to 0.13
      to 0.53. Two of five patients had UTI episodes since transplantation. Patient A
      showed Banff Type 1A acute T-cell mediated rejected approximately two months
      after transplant, but subsequent biopsies have been negative for rejection.
      Patient A also required a vesicostomy revision approximately two months after
      transplant and balloon dilation of UVJ anastomosis three months after transplant.
      DISCUSSION: Vesicostomy is an especially attractive option to manage children
      with small bladders to accommodate the high urinary output that occurs after
      transplantation in infants who require an adult kidney. Recent advances in
      antenatal management such as amnioinfusion for oligohydramnios have made
      significant impacts in pulmonary and renal management of this patient population
      over recent years. CONCLUSION: This report provides further support for the use
      of vesicostomy as an option for surgical management of patients with renal
      failure with oligohydramnios and severe obstructive lesions identified
      antenatally. It also indicates the need to update the criteria for antenatal
      management of oligohydramnios in obstructive and anephric patients.

PMID- 30228094
TI  - Association between renal mass biopsy and upstaging to perinephric fat
      involvement in a contemporary cohort of patients with clinical T1a renal cell
      carcinoma.
AB  - BACKGROUND: Although tumor tract seeding from renal mass biopsy (RMB) is
      exceedingly rare, the possibility of tumor capsule violation from RMB leading to
      perinephric fat invasion has not been quantified. We evaluated the association
      between RMB and perinephric fat invasion in patients with clinical T1a renal cell
      carcinoma who underwent partial or radical nephrectomy. MATERIALS AND METHODS: We
      reviewed the National Cancer Database from 2010-2013 and identified patients who
      underwent surgery for clinical T1a tumors. Patients were classified as upstaged
      only if final pathology demonstrated perinephric invasion only (pT3a). Mixed
      effect logistic regression analysis was performed on inverse probability weighted
      matched groups to identify predictors of perinephric fat invasion. Multivariable
      Cox proportional hazards models and Kaplan-Meier survival curves were used to
      evaluate overall survival (OS). RESULTS: A total of 24,548 patients met our
      inclusion criteria. Pathologic upstaging to pT3a perinephric fat involvement
      occurred in 1.2% of patients. This rate of upstaging was 1.1% in the no biopsy
      group compared with 2.1% in patients who underwent RMB (P < 0.01). In
      multivariable logistic model, RMB was associated with pT3a perinephric fat
      upstaging (OR 1.69, 95% CI 1.17-2.44, P < 0.01). Upstaging to pT3a was also
      associated with worse OS (HR 1.71, 95% CI 1.13-2.60, P = 0.01). Kaplan-Meier
      survival curves demonstrated similar OS estimates in patients upstaged to pT3a
      disease, irrespective of undergoing RMB or not (Log-Rank = 0.87). CONCLUSION: RMB
      was associated with increased rate of upstaging to pT3a perinephric fat
      involvement in clinical T1a RCC. This effect is small with unclear clinical
      significance. This is perhaps balanced by the importance of the information
      acquired from biopsies. Future studies are needed to elucidate clinical
      significance of this finding.

PMID- 30228093
TI  - Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and
      Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis
      and Autophagy in Mice.
AB  - BACKGROUND: Recent evidence has demonstrated that interleukin 12p35 knockout (IL
      12p35 KO) is involved in cardiac diseases by regulating the inflammatory
      response. The involvement of inflammatory cells has also been observed in
      doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate whether
      IL-12p35 KO affects DOX-induced cardiac injury and the underlying mechanisms.
      METHODS: First, the effect of DOX treatment on cardiac IL-12p35 expression was
      assessed. In addition, to investigate the effect of IL-12p35 KO on DOX-induced
      cardiac injury, IL-12p35 KO mice were treated with DOX. Because IL-12p35 is the
      mutual subunit of IL-12 and IL-35, to determine the cytokine that mediates the
      effect of IL-12p35 KO on DOX-induced cardiac injury, mice were given phosphate
      buffered saline (PBS), mouse recombinant IL-12 (rIL-12) or rIL-35 before
      treatment with DOX. RESULTS: DOX treatment significantly increased the level of
      cardiac IL-12p35 expression. In addition, IL-12p35 KO mice exhibited higher serum
      and heart lactate dehydrogenase levels, higher serum and heart creatine kinase
      myocardial bound levels, and greater cardiac dysfunction than DOX-treated mice.
      Furthermore, IL-12p35 KO further increased M1 macrophage and decreased M2
      macrophage differentiation, aggravated the imbalance of oxidants and
      antioxidants, and further activated the mitochondrial apoptotic pathway and
      endoplasmic reticulum stress autophagy pathway. Both rIL-12 and rIL-35 protected
      against DOX-induced cardiac injury by alleviating the inflammatory response,
      oxidative stress, apoptosis and autophagy. CONCLUSIONS: IL-12p35 KO aggravated
      DOX-induced cardiac injury by amplifying the levels of inflammation, oxidative
      stress, apoptosis and autophagy. (234 words).

PMID- 30228095
TI  - Abbreviated CT protocol for postoperative surveillance of renal cancer.
AB  - INTRODUCTION: Postoperative surveillance protocols after nephrectomy for kidney
      cancer include periodic computed tomography (CT) scans of the chest and abdomen.
      A single study exposes the patient to 21 mSv (equivalent to 7-year exposure to
      natural background radiation). The objective of this study was to evaluate the
      hypothesis that an abbreviated CT protocol restricted to the chest and upper
      abdomen (i.e., to the level of the intervertebral disk L3-L4) is sufficient for
      routine postnephrectomy follow-up as it detects most tumor recurrence with lower
      radiation exposure. METHODS: We identified 493 patients treated with radical or
      partial nephrectomy for localized kidney cancer and followed with periodic CT
      scans of the chest and abdomen for prolonged periods. The frequency and location
      of cancer recurrence were documented. The ratio of infield recurrence for the
      complete chest, and abdomen and for the abbreviated protocol was recorded. The
      decrease in radiation exposure was calculated. RESULTS: At a median follow up of
      96 months, 82 patients (16.6%) developed recurrence. The frequent sites of
      recurrence were the lungs (53), the bones (9), and local recurrence (22).
      Complete chest and abdominal CT identified 78 of the recurrences (95%) and the
      abbreviated protocol identifying all but one of these (94%). The abbreviated
      protocol exposed the patient to 48% (standard deviation 4.3%) less radiation
      compared to the full protocol. CONCLUSIONS: Using an abbreviated CT protocol that
      includes the chest and upper abdomen for surveillance after surgery of localized
      kidney cancer decreases radiation exposure by half with only a minor decrease in
      the sensitivity of the examination.

PMID- 30228096
TI  - Risk prediction models for cancer-specific survival following cytoreductive
      nephrectomy in the contemporary era.
AB  - INTRODUCTION: To develop a risk-stratification model for cancer-specific survival
      (CSS) following cytoreductive nephrectomy (CN) in the contemporary era. MATERIALS
      AND METHODS: A retrospective review was performed of 313 patients who underwent
      CN for M1 renal cell carcinoma (RCC) from 1990 to 2010. To account for the
      introduction of targeted therapies, timing of surgery was classified as
      immunotherapy era (1990-2004) or contemporary era (2005-2010). Risk scores were
      developed to predict CSS using Cox proportional hazards regression models.
      RESULTS: A total of 215 (69%) and 98 (31%) patients were treated in the
      immunotherapy and contemporary eras, respectively. Median follow-up among
      survivors was 9.6 years, during which time 291 patients died, including 279 from
      RCC. On multivariable analysis limited to preoperative features, age >= 75,
      (hazard ratio [HR] 1.9), female sex (HR 1.9), constitutional symptoms (HR 1.61),
      radiographic lymphadenopathy (HR 1.59), and IVC tumor thrombus (HR 1.65) were
      significantly associated with CSS. On multivariable analysis including pathologic
      features, the features above as well as coagulative necrosis (HR 1.51) and
      sarcomatoid differentiation (HR 1.44) were significantly associated with CSS (all
      P < 0.05). Risk scores were developed for each model and used to predict CSS
      according to era. Decision curve analysis revealed that the preoperative risk
      score conferred a net benefit over a treat-all or treat-none approach beyond a 1
      year cancer-specific mortality threshold of 25%. CONCLUSIONS: We developed risk
      scores to predict CSS for patients treated with CN in the contemporary era.
      Patients with poor predicted survival may consider avoiding CN as initial
      management.

PMID- 30228098
TI  - Don't forget about neuromuscular disorders!

PMID- 30228097
TI  - Reported rates of clostridium difficile following radical cystectomy in national
      datasets compared to individual institutions.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is an important cause of
      hospital acquired morbidity with implications for quality of care. Radical
      cystectomy is a surgical procedure associated with high rates of morbidity one of
      which is a high rate of CDI. The rate of CDI among patients undergoing radical
      cystectomy may be estimated based on the reports from single institutions or by
      querying national databases. This study aims to compare rates of CDI reported in
      single institution series with rates obtained from national datasets. METHODS: A
      search was conducted on PubMed and Google Scholar using the terms
      "cystectomy+difficile" and "cystectomy+complication." Three hundred fifty
      articles were screened and 46 met criteria for inclusion based on the presence of
      specific rates of C. difficile following radical cystectomy. In the case of
      articles reporting on the same database, only the article with a larger sample
      size was included in the pooled analysis. One study reviewing a single
      institution was excluded from pooled analysis because it did not relate the rate
      of CDI specifically with cystectomy. Multi-institutional studies were not
      included in pooled analysis. RESULTS: After exclusion of repeated data and multi
      institutional studies, the pooled analysis consisted of 39 studies. Thirty five
      articles reported rates of CDI in single institutions and 4 articles reported
      rates found in national databases. Studies focusing on a single institution
      reported an average 5.02% (standard deviation = 4.88) incidence of CDI, compared
      to an average of 1.92% (standard deviation = 0.22) in databases. The rate of CDI
      found by totaling patients and incidence of infection found that databases show a
      rate of 1.95%, while institutions show a rate of 4.11% (P < 0.0000001).
      CONCLUSION: The rate of CDI following radical cystectomy may be underestimated in
      national databases. This has implications for the development of health policy
      and quality measures based on the rate of CDI.

PMID- 30228099
TI  - ERJ September Podcast: Challenges and perspectives in obstructive sleep apnoea.

PMID- 30228100
TI  - Evaluation of the nutrient content of yogurts: a comprehensive survey of yogurt
      products in the major UK supermarkets.
AB  - OBJECTIVES: To comprehensively survey the sugar and nutrient contents of yogurt
      products available in UK supermarkets, in particular those marketed to children.
      DESIGN: A cross-sectional survey of yogurt products available in the UK's
      supermarkets in November 2016. METHODS: Data were collected from five major
      online UK supermarkets and a process flow strategy was used to place yogurts into
      eight categories: children's, dairy alternatives, dessert, drinks, fruit,
      flavoured, natural/Greek style and organic. A comprehensive database of product
      information for 921 unique products was created and analysed. RESULTS: The total
      sugar, fat, protein, calcium and energy contents were highly variable across
      categories, and the ranges were extremely broad. Although lower than the dessert
      category, the medians (range) of the total sugar content of children's (10.8
      g/100 g (4.8-14.5)), fruit (11.9 g/100 g (4.6-21.3)), flavoured (12.0 g/100 g
      (0.1-18.8)) and organic (13.1 g/100 g (3.8-16.9)) yogurt products were all well
      above 10 g/100 g, and represented >45% of total energy. Only two out of 101
      children's yogurt and fromage frais products surveyed qualified as low sugar (<=5
      g/100 g). Natural/Greek yogurts had dramatically lower sugar contents (5.0 g/100
      g (1.6, 9.5), largely lactose) than all other categories. While low-fat (<3 g/100
      g) products had less sugar and energy than higher fat yogurts, nonetheless 55%
      (285 of 518 low-fat yogurts) contained between 10 and 20 g sugar/100 g. Within
      the children's category, fromage frais had higher protein (5.3 g/100 g (3.3, 8.6)
      vs 3.2 (2.8, 7.1); p<0.0001) and calcium contents (150 mg/100 g (90, 240) vs
      130.5 mg/100 g (114, 258); p=0.0015) than yogurts. CONCLUSIONS: While there is
      good evidence that yogurt can be beneficial to health, products on the market
      vary widely in total sugars. Fewer than 9%, and only 2% of the children's,
      products surveyed were low enough in sugar to earn 'green' in UK front of the
      pack labelling. Reformulation for the reduction of free sugars in yogurts is
      warranted.

PMID- 30228101
TI  - Sterols regulate endocytic pathways during flg22-induced defense responses in
      Arabidopsis.
AB  - The plant transmembrane receptor kinase FLAGELLIN SENSING 2 (FLS2) is crucial for
      innate immunity. Although previous studies have reported FLS2-mediated signal
      transduction and endocytosis via the clathrin-mediated pathway, whether
      additional endocytic pathways affect FLS2-mediated defense responses remains
      unclear. Here, we show that the Arabidopsis thaliana sterol-deficient mutant
      steroid methyltransferase 1 displays defects in immune responses induced by the
      flagellin-derived peptide flg22. Variable-angle total internal reflection
      fluorescence microscopy (VA-TIRFM) coupled with single-particle tracking showed
      that the spatiotemporal dynamics of FLS2-GFP changed on a millisecond time scale
      and that the FLS2-GFP dwell time at the plasma membrane increased in cells
      treated with a sterol-extracting reagent when compared with untreated
      counterparts. We further demonstrate that flg22-induced FLS2 clustering and
      endocytosis involves the sterol-associated endocytic pathway, which is distinct
      from the clathrin-mediated pathway. Moreover, flg22 enhanced the colocalization
      of FLS2-GFP with the membrane microdomain marker Flot 1-mCherry and FLS2
      endocytosis via the sterol-associated pathway. This indicates that plants may
      respond to pathogen attacks by regulating two different endocytic pathways. Taken
      together, our results suggest the key role of sterol homeostasis in flg22-induced
      plant defense responses.

PMID- 30228103
TI  - Secretory pathway calcium ATPase 1 (SPCA1) controls mouse neural tube closure by
      regulating cytoskeletal dynamics.
AB  - Neural tube closure relies on the apical constriction of neuroepithelial cells.
      Research in frog and fly embryos has found links between the levels of
      intracellular calcium, actomyosin dynamics and apical constriction. However,
      genetic evidence for a role of calcium in apical constriction during mammalian
      neurulation is still lacking. Secretory pathway calcium ATPase (SPCA1) regulates
      calcium homeostasis by pumping cytosolic calcium into the Golgi apparatus. Loss
      of function in Spca1 causes cranial exencephaly and spinal cord defects in mice,
      phenotypes previously ascribed to apoptosis. However, our characterization of a
      novel allele of Spca1 revealed that neurulation defects in Spca1 mutants are not
      due to cell death, but rather to a failure of neuroepithelial cells to apically
      constrict. We show that SPCA1 influences cell contractility by regulating myosin
      II localization. Furthermore, we found that loss of Spca1 disrupts actin dynamics
      and the localization of the actin remodeling protein cofilin 1. Taken together,
      our results provide evidence that SPCA1 promotes neurulation by regulating the
      cytoskeletal dynamics that promote apical constriction and identify cofilin 1 as
      a downstream effector of SPCA1 function.

PMID- 30228102
TI  - Leukocyte receptor tyrosine kinase interacts with secreted midkine to promote
      survival of migrating neural crest cells.
AB  - Neural crest cells migrate long distances throughout the embryo and rely on
      extracellular signals that attract, repel and/or stimulate survival to ensure
      proper contribution to target derivatives. Here, we show that leukocyte receptor
      tyrosine kinase (LTK), an ALK-type receptor tyrosine kinase, is expressed by
      neural crest cells during early migratory stages in chicken embryos. Loss of LTK
      in the cranial neural crest impairs migration and results in increased levels of
      apoptosis. Conversely, midkine, previously proposed as a ligand for ALK, is
      secreted by the non-neural ectoderm during early neural crest migratory stages
      and internalized by neural crest cells in vivo Similar to loss of LTK, loss of
      midkine reduces survival of the migratory neural crest. Moreover, we show by
      proximity ligation and co-immunoprecipitation assays that midkine binds to LTK.
      Taken together, these results suggest that LTK in neural crest cells interacts
      with midkine emanating from the non-neural ectoderm to promote cell survival,
      revealing a new signaling pathway that is essential for neural crest development.

PMID- 30228106
TI  - Coping methods used by emergency department nurses after a workplace violence
      experience could influence their intention to leave the hospital.

PMID- 30228105
TI  - Developing and sustaining a Community of Practice through Twitter for work-based
      learning.

PMID- 30228104
TI  - Midface and upper airway dysgenesis in FGFR2-related craniosynostosis involves
      multiple tissue-specific and cell cycle effects.
AB  - Midface dysgenesis is a feature of more than 200 genetic conditions in which
      upper airway anomalies frequently cause respiratory distress, but its etiology is
      poorly understood. Mouse models of Apert and Crouzon craniosynostosis syndromes
      exhibit midface dysgenesis similar to the human conditions. They carry activating
      mutations of Fgfr2, which is expressed in multiple craniofacial tissues during
      development. Magnetic resonance microscopy of three mouse models of Apert and
      Crouzon syndromes revealed decreased nasal passage volume in all models at birth.
      Histological analysis suggested overgrowth of the nasal cartilage in the two
      Apert syndrome mouse models. We used tissue-specific gene expression and
      transcriptome analysis to further dissect the structural, cellular and molecular
      alterations underlying midface and upper airway dysgenesis in Apert Fgfr2+/S252W
      mutants. Cartilage thickened progressively during embryogenesis because of
      increased chondrocyte proliferation in the presence of Fgf2 Oral epithelium
      expression of mutant Fgfr2, which resulted in a distinctive nasal septal fusion
      defect, and premature facial suture fusion contributed to the overall
      dysmorphology. Midface dysgenesis in Fgfr2-related craniosynostosis is a complex
      phenotype arising from the combined effects of aberrant signaling in multiple
      craniofacial tissues.

PMID- 30228107
TI  - How to appraise quantitative research.

PMID- 30228109
TI  - Sexually transmitted infections during pregnancy and subsequent risk of
      stillbirth and infant mortality in Kenya: a prospective study.
AB  - OBJECTIVES: We evaluated the relationship of sexually transmitted infections
      (STIs) and genital infections during pregnancy and subsequent risk for infant
      mortality and stillbirth. METHODS: This was a nested longitudinal analysis using
      data from a study of peripartum HIV acquisition in Kenya. In the parent study,
      HIV-uninfected women were enrolled during pregnancy and followed until 9 months
      postpartum. For this analysis, women who tested positive for HIV at any point,
      had a non-singleton pregnancy or a spontaneous abortion <20 weeks were excluded.
      At enrolment, laboratory methods were used to screen for bacterial vaginosis
      (BV), vaginal yeast, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and
      Trichomonas vaginalis (TV). Syphilis was diagnosed using rapid plasma reagin
      testing and genital ulcer disease (GUD) identified by clinical examination.
      Treatment of laboratory-confirmed STIs and syndromic management was provided per
      Kenyan national guidelines. Predictors of stillbirth and infant mortality were
      determined using logistic regression and Cox proportional hazards models.
      RESULTS: Overall, among 1221 women, 55% had STIs or genital infections detected:
      vaginal yeast (25%), BV (22%), TV (6%), CT (5%), NG (2%) and syphilis (1%). Among
      women with STIs/genital infections (n=592), 34% had symptoms. Overall, 19/1221
      (2%) women experienced stillbirths. Among 1202 live births, 34 infant deaths
      occurred (incidence 4.0 deaths per 100 person-years, 95% CI 2.8 to 5.5). After
      adjustment for maternal age, education and study site, stillbirth was associated
      with maternal GUD (adjusted OR=9.19, 95% CI1.91 to 44.35, p=0.006). Maternal NG
      was associated with infant mortality (adjusted HR=3.83, 95% CI1.16 to 12.68,
      p=0.028); there was some evidence that maternal CT was associated with infant
      mortality. Stillbirth or infant mortality were not associated with other genital
      infections. CONCLUSIONS: STIs and genital infections were common, frequently
      asymptomatic and some associated with stillbirth or infant mortality. Expediting
      diagnosis and treatment of STIs in pregnancy may improve infant outcomes.

PMID- 30228111
TI  - Incorporating the patient experience into clinical guidelines: recommendations
      for researchers and guideline developers.

PMID- 30228110
TI  - Vascular Dysfunction, Oxidative Stress, and Inflammation in Autosomal Dominant
      Polycystic Kidney Disease.
AB  - BACKGROUND AND OBJECTIVES: Both increased arterial stiffness and vascular
      endothelial dysfunction are evident in patients with autosomal dominant
      polycystic kidney disease, even early in the course of the disease when kidney
      function in preserved. Vascular dysfunction in autosomal dominant polycystic
      kidney disease is thought to be related to vascular oxidative stress and
      inflammation, but direct evidence is lacking. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We assessed carotid-femoral pulse-wave velocity (arterial
      stiffness) and brachial artery flow-mediated dilation (vascular endothelial
      function) in participants with early-stage autosomal dominant polycystic kidney
      disease (eGFR>=60 ml/min per 1.73 m2) and a history of controlled hypertension
      and in healthy controls. Brachial artery flow-mediated dilation was also assessed
      after infusion of ascorbic acid to inhibit vascular oxidative stress compared
      with saline. Vascular endothelial cells were collected from a peripheral vein to
      measure expression of proteins, and circulating markers were also assessed by
      ELISA or liquid chromatography-tandem mass spectrometry. RESULTS: In total, 61
      participants with autosomal dominant polycystic kidney disease (34+/-9 years old
      [mean+/-SD]) and 19 healthy controls (30+/-5 years old) were studied. Carotid
      femoral pulse-wave velocity was higher in participants with autosomal dominant
      polycystic kidney disease compared with healthy controls (650+/-131 versus 562+/
      81 cm/s; P=0.007). Brachial artery flow-mediated dilation was 8.2%+/-5.8% in
      participants with autosomal dominant polycystic kidney disease and 10.8%+/-4.7%
      in controls (P=0.08). Among participants with autosomal dominant polycystic
      kidney disease, flow-mediated dilation increased from 7.7%+/-4.5% to 9.4%+/-5.2%
      with ascorbic acid, a difference of 1.72 (95% confidence interval, 0.80 to 2.63),
      whereas in control participants, flow-mediated dilation decreased
      nonsignificantly from 10.8%+/-4.7% to 10.6%+/-5.4%, a difference of -0.20 (95%
      confidence interval, -1.24 to 0.84; P interaction =0.02). Endothelial cell
      protein expression of NF-kappaB was greater in participants with autosomal
      dominant polycystic kidney disease (0.48+/-0.12 versus 0.41+/-0.10 [intensity
      versus human umbilical vein endothelial cell control]; P=0.03). However,
      circulating oxidative stress markers and bioactive lipid mediators did not
      significantly differ according to the autosomal dominant polycystic kidney
      disease diagnosis. CONCLUSIONS: These results provide support for the hypothesis
      that vascular oxidative stress and inflammation develop with autosomal dominant
      polycystic kidney disease. PODCAST: This article contains a podcast at
      https://www.asn
      online.org/media/podcast/CJASN/2018_09_18_CJASNPodcast_18_10_.mp3.

PMID- 30228112
TI  - Tumor Growth Inhibition Modelling Based on Receptor Occupancy and Biomarker
      Activity of a New Bcl-2 Inhibitor in Mice.
AB  - The Bcl-2 inhibitor S 55746 ((S)-N-(4-hydroxyphenyl)-3-(6-(3-(morpholinomethyl)
      1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzo[d][1,3]dioxol-5-yl)-N-phenyl
      5,6,7,8-tetrahydroindolizine-1-carboxamide) is able to restore apoptosis
      functions impaired by tumorigenesis in mice. Data from pharmacokinetic (PK),
      biomarker, and tumor growth studies in a xenograft mouse model were considered
      for population modeling. The aim of the modeling exercise was to link the
      kinetics of the drug to the biomarker and tumor-size time profiles to better
      understand its dose-effect relationship. The PK, caspase kinetics, and tumor
      dynamics were successfully characterized by the proposed pharmacokinetic
      pharmacodynamic model. The nonlinear plasma PK was best described by a two
      compartment disposition model with both saturable absorption and elimination.
      Caspase was activated above the effective drug-concentration threshold (CTHRE ),
      at which near-maximal activity was reached. Increasing the dose did not increase
      the activation but better sustained it. Tumor growth followed a biphasic pattern,
      with caspase having an all-or-none inhibiting effect, consistent with the
      bistability property of the caspase pathway. For tumor eradication, the CTHRE in
      plasma was 2876 ng ml-1, and the relative caspase activity threshold (CaspTHRE)
      was 46.5. There was a strong relationship between the time spent above these
      thresholds and tumor growth inhibition. Tumor growth was inhibited by 50% when
      CaspTHRE was exceeded 13.8% of the time and when CTHRE was exceeded 8.1% of the
      time per dosing. This semimechanistic approach, based on experimental mice data
      and in vitro parameters, provides an interesting tool to quantify or simulate
      antitumor effects and, eventually, to plan phase 1 studies.

PMID- 30228108
TI  - Identification of Key Enzymes for Pectin Synthesis in Seed Mucilage.
AB  - Pectin is a vital component of the plant cell wall and provides the molecular
      glue that maintains cell-cell adhesion, among other functions. As the most
      complex wall polysaccharide, pectin is composed of several covalently linked
      domains, such as homogalacturonan (HG) and rhamnogalacturonan I (RG I). Pectin
      has widespread uses in the food industry and has emerging biomedical
      applications, but its synthesis remains poorly understood. For instance, the
      enzymes that catalyze RG I elongation remain unknown. Recently, a coexpression-
      and sequence-based MUCILAGE-RELATED (MUCI) reverse genetic screen uncovered
      hemicellulose biosynthetic enzymes in the Arabidopsis (Arabidopsis thaliana) seed
      coat. Here, we use an extension of this strategy to identify MUCI70 as the
      founding member of a glycosyltransferase family essential for the accumulation of
      seed mucilage, a gelatinous wall rich in unbranched RG I. Detailed biochemical
      and histological characterization of two muci70 mutants and two
      galacturonosyltransferase11 (gaut11) mutants identified MUCI70 and GAUT11 as
      required for two distinct RG I domains in seed mucilage. We demonstrate that,
      unlike MUCI70, GAUT11 catalyzes HG elongation in vitro and, thus, likely is
      required for the synthesis of an HG region important for RG I elongation.
      Analysis of a muci70 gaut11 double mutant confirmed that MUCI70 and GAUT11 are
      indispensable for the production and release of the bulk of mucilage RG I and for
      shaping the surface morphology of seeds. In addition, we uncover relationships
      between pectin and hemicelluloses and show that xylan is essential for the
      elongation of at least one RG I domain.

PMID- 30228113
TI  - Higher Activity of Alcohol Dehydrogenase Is Correlated with Hepatic Fibrogenesis.
AB  - Hepatofibrosis can progress to cirrhosis and hepatocellular carcinoma (HCC).
      Prevention, stabilization, and reversal of disease progression are vital for
      patients with hepatofibrosis, and identifying the risk factors for hepatofibrosis
      is urgently needed. In this study, we examined the activities of alcohol
      dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the fibrotic livers
      of HCC patients (n = 88) and comparied these results with activities in patients
      with normal livers (n = 74). A fibrosis-carcinoma rat model was used to study the
      activity of ADH in fibrosis and HCC and the relationship between innate ADH
      activity and the extent of hepatofibrosis or HCC. Substantial interindividual
      variations were found in the activities of ADH and ALDH in normal livers. The
      activity levels of total ADH, ADHI, and ADHII in fibrotic livers were
      significantly higher than those in normal livers (P < 0.001), whereas the
      activity of ALDH was slightly greater. The positive rates of ADHI and ADHII were
      84.1% and 77.3%, respectively; the areas under the receiver operator
      characteristics (ROC) curve were 0.943 and 0.912, respectively. For the rat model
      compared with controls, ADH activity in liver was significantly increased at the
      fibrotic and HCC stages, and no significant difference was noted between ADH
      activity in the liver at these two stages. The innate activity of ADH in serum
      was well correlated with the extent of hepatofibrosis as indicated by Masson
      area%, Ki67+%, proliferating cell nuclear antigen +%, and GST-p average density
      at fibrotic stage but not at HCC stage. A higher level of activity of ADH is a
      risk factor for hepatofibrogenesis and might be a prevention target for
      hepatofibrosis.

PMID- 30228114
TI  - Two-level masers as heat-to-work converters.
AB  - Heat engines, which cyclically transform heat into work, are ubiquitous in
      technology. Lasers and masers may be viewed as heat engines that rely on
      population inversion or coherence in the active medium. Here we put forward an
      unconventional paradigm of a remarkably simple and robust electromagnetic heat
      powered engine that bears basic differences to any known maser or laser: The
      proposed device makes use of only one Raman transition and does not rely on
      population inversion or coherence in its two-level working medium. Nor does it
      require any coherent driving. The engine can be powered by the ambient
      temperature difference between the sky and the ground surface. Its autonomous
      character and "free" power source make this engine conceptually and
      technologically enticing.

PMID- 30228115
TI  - Intrinsic spin of elastic waves.
AB  - Unveiling spins of physical systems usually gives people a fundamental
      understanding of the geometrical properties of waves from classical to quantum
      aspects. A great variety of research has shown that transverse waves can possess
      nontrivial spins and spin-related properties naturally. However, until now, we
      still lack essential physical insights about the spin nature of longitudinal
      waves. Here, demonstrated by elastic waves, we uncover spins for longitudinal
      waves and the mixed longitudinal-transverse waves that play essential roles in
      spin-momentum locking. Based on this spin perspective, several abnormal phenomena
      beyond pure transverse waves are attributed to the hybrid spin induced by mixed
      longitudinal-transverse waves. The unique hybrid spin reveals the complex spin
      essence in elastic waves and advances our understanding about their fundamental
      geometrical properties. We also show that these spin-dependent phenomena can be
      exploited to control the wave propagation, such as nonsymmetric elastic wave
      excitation by spin pairs, a unidirectional Rayleigh wave, and spin-selected
      elastic wave routing. These findings are generally applicable for wave cases with
      longitudinal and transverse components.

PMID- 30228117
TI  - ACSS2 promotes systemic fat storage and utilization through selective regulation
      of genes involved in lipid metabolism.
AB  - Acetyl-CoA synthetase 2 (ACSS2) is a conserved nucleocytosolic enzyme that
      converts acetate to acetyl-CoA. Adult mice lacking ACSS2 appear phenotypically
      normal but exhibit reduced tumor burdens in mouse models of liver cancer. The
      normal physiological functions of this alternate pathway of acetyl-CoA synthesis
      remain unclear, however. Here, we reveal that mice lacking ACSS2 exhibit a
      significant reduction in body weight and hepatic steatosis in a diet-induced
      obesity model. ACSS2 deficiency reduces dietary lipid absorption by the intestine
      and also perturbs repartitioning and utilization of triglycerides from adipose
      tissue to the liver due to lowered expression of lipid transporters and fatty
      acid oxidation genes. In this manner, ACSS2 promotes the systemic storage or
      metabolism of fat according to the fed or fasted state through the selective
      regulation of genes involved in lipid metabolism. Thus, targeting ACSS2 may offer
      a therapeutic benefit for the treatment of fatty liver disease.

PMID- 30228116
TI  - Amycomicin is a potent and specific antibiotic discovered with a targeted
      interaction screen.
AB  - The rapid emergence of antibiotic-resistant pathogenic bacteria has accelerated
      the search for new antibiotics. Many clinically used antibacterials were
      discovered through culturing a single microbial species under nutrient-rich
      conditions, but in the environment, bacteria constantly encounter poor nutrient
      conditions and interact with neighboring microbial species. In an effort to
      recapitulate this environment, we generated a nine-strain actinomycete community
      and used 16S rDNA sequencing to deconvolute the stochastic production of
      antimicrobial activity that was not observed from any of the axenic cultures. We
      subsequently simplified the community to just two strains and identified
      Amycolatopsis sp. AA4 as the producing strain and Streptomyces coelicolor M145 as
      an inducing strain. Bioassay-guided isolation identified amycomicin (AMY), a
      highly modified fatty acid containing an epoxide isonitrile warhead as a potent
      and specific inhibitor of Staphylococcus aureus Amycomicin targets an essential
      enzyme (FabH) in fatty acid biosynthesis and reduces S. aureus infection in a
      mouse skin-infection model. The discovery of AMY demonstrates the utility of
      screening complex communities against specific targets to discover small-molecule
      antibiotics.

PMID- 30228118
TI  - Genomic responses to selection for tame/aggressive behaviors in the silver fox
      (Vulpes vulpes).
AB  - Animal domestication efforts have led to a shared spectrum of striking behavioral
      and morphological changes. To recapitulate this process, silver foxes have been
      selectively bred for tame and aggressive behaviors for more than 50 generations
      at the Institute for Cytology and Genetics in Novosibirsk, Russia. To understand
      the genetic basis and molecular mechanisms underlying the phenotypic changes, we
      profiled gene expression levels and coding SNP allele frequencies in two brain
      tissue specimens from 12 aggressive foxes and 12 tame foxes. Expression analysis
      revealed 146 genes in the prefrontal cortex and 33 genes in the basal forebrain
      that were differentially expressed, with a 5% false discovery rate (FDR). These
      candidates include genes in key pathways known to be critical to neurologic
      processing, including the serotonin and glutamate receptor pathways. In addition,
      295 of the 31,000 exonic SNPs show significant allele frequency differences
      between the tame and aggressive populations (1% FDR), including genes with a role
      in neural crest cell fate determination.

PMID- 30228119
TI  - Conductively coupled flexible silicon electronic systems for chronic neural
      electrophysiology.
AB  - Materials and structures that enable long-term, intimate coupling of flexible
      electronic devices to biological systems are critically important to the
      development of advanced biomedical implants for biological research and for
      clinical medicine. By comparison with simple interfaces based on arrays of
      passive electrodes, the active electronics in such systems provide powerful and
      sometimes essential levels of functionality; they also demand long-lived, perfect
      biofluid barriers to prevent corrosive degradation of the active materials and
      electrical damage to the adjacent tissues. Recent reports describe strategies
      that enable relevant capabilities in flexible electronic systems, but only for
      capacitively coupled interfaces. Here, we introduce schemes that exploit patterns
      of highly doped silicon nanomembranes chemically bonded to thin, thermally grown
      layers of SiO2 as leakage-free, chronically stable, conductively coupled
      interfaces. The results can naturally support high-performance, flexible silicon
      electronic systems capable of amplified sensing and active matrix multiplexing in
      biopotential recording and in stimulation via Faradaic charge injection.
      Systematic in vitro studies highlight key considerations in the materials science
      and the electrical designs for high-fidelity, chronic operation. The results
      provide a versatile route to biointegrated forms of flexible electronics that can
      incorporate the most advanced silicon device technologies with broad applications
      in electrical interfaces to the brain and to other organ systems.

PMID- 30228120
TI  - Ultradian calcium rhythms in the paraventricular nucleus and subparaventricular
      zone in the hypothalamus.
AB  - The suprachiasmatic nucleus (SCN), the master circadian clock in mammals, sends
      major output signals to the subparaventricular zone (SPZ) and further to the
      paraventricular nucleus (PVN), the neural mechanism of which is largely unknown.
      In this study, the intracellular calcium levels were measured continuously in
      cultured hypothalamic slices containing the PVN, SPZ, and SCN. We detected
      ultradian calcium rhythms in both the SPZ-PVN and SCN regions with periods of 0.5
      4.0 hours, the frequency of which depended on the local circadian rhythm in the
      SPZ-PVN region. The ultradian rhythms were synchronous in the entire SPZ-PVN
      region and a part of the SCN. Because the ultradian rhythms were not detected in
      the SCN-only slice, the origin of ultradian rhythm is the SPZ-PVN region. In
      association with an ultradian bout, a rapid increase of intracellular calcium in
      a millisecond order was detected, the frequency of which determined the amplitude
      of an ultradian bout. The synchronous ultradian rhythms were desynchronized and
      depressed by a sodium channel blocker tetrodotoxin, suggesting that a
      tetrodotoxin-sensitive network is involved in synchrony of the ultradian bouts.
      In contrast, the ultradian rhythm is abolished by glutamate receptor blockers,
      indicating the critical role of glutamatergic mechanism in ultradian rhythm
      generation, while a GABAA receptor blocker increased the frequency of ultradian
      rhythm and modified the circadian rhythm in the SCN. A GABAergic network may
      refine the circadian output signals. The present study provides a clue to
      unraveling the loci and network mechanisms of the ultradian rhythm.

PMID- 30228121
TI  - GIRK currents in VTA dopamine neurons control the sensitivity of mice to cocaine
      induced locomotor sensitization.
AB  - GABABR-dependent activation of G protein-gated inwardly rectifying potassium
      channels (GIRK or KIR3) provides a well-known source of inhibition in the brain,
      but the details on how this important inhibitory pathway affects neural circuits
      are lacking. We used sorting nexin 27 (SNX27), an endosomal adaptor protein that
      associates with GIRK2c and GIRK3 subunits, to probe the role of GIRK channels in
      reward circuits. A conditional knockout of SNX27 in both substantia nigra pars
      compacta and ventral tegmental area (VTA) dopamine neurons leads to markedly
      smaller GABABR- and dopamine D2R-activated GIRK currents, as well as to
      suprasensitivity to cocaine-induced locomotor sensitization. Expression of the
      SNX27-insensitive GIRK2a subunit in SNX27-deficient VTA dopamine neurons restored
      GIRK currents and GABABR-dependent inhibition of spike firing, while also
      resetting the mouse's sensitivity to cocaine-dependent sensitization. These
      results establish a link between slow inhibition mediated by GIRK channels in VTA
      dopamine neurons and cocaine addiction, revealing a therapeutic target for
      treating addiction.

PMID- 30228122
TI  - Targeting intramolecular proteinase NS2B/3 cleavages for trans-dominant
      inhibition of dengue virus.
AB  - Many positive-strand RNA viruses translate their genomes as single polyproteins
      that are processed by host and viral proteinases to generate all viral protein
      products. Among these is dengue virus, which encodes the serine proteinase NS2B/3
      responsible for seven different cleavages in the polyprotein. NS2B/3 has been the
      subject of many directed screens to find chemical inhibitors, of which the
      compound ARDP0006 is among the most effective at inhibiting viral growth. We show
      that at least three cleavages in the dengue polyprotein are exclusively
      intramolecular. By definition, such a cis-acting defect cannot be rescued in
      trans This creates the possibility that a drug-susceptible or inhibited
      proteinase can be genetically dominant, inhibiting the outgrowth of drug
      resistant virus via precursor accumulation. Indeed, an NS3-G459L variant that is
      incapable of cleavage at the internal NS3 junction dominantly inhibited negative
      strand RNA synthesis of wild-type virus present in the same cell. This internal
      NS3 cleavage site is the junction most inhibited by ARDP0006, making it likely
      that the accumulation of toxic precursors, not inhibition of proteolytic activity
      per se, explains the antiviral efficacy of this compound in restraining viral
      growth. We argue that intramolecularly cleaving proteinases are promising drug
      targets for viruses that encode polyproteins. The most effective inhibitors will
      specifically target cleavage sites required for processing precursors that exert
      trans-dominant inhibition.

PMID- 30228124
TI  - Medical associate professions: how physician associate and similar roles are
      developing, and what that means for doctors.

PMID- 30228123
TI  - Identification of cell populations necessary for leaf-to-leaf electrical
      signaling in a wounded plant.
AB  - The identity of the cell files necessary for the leaf-to-leaf transmission of
      wound signals plants has been debated for decades. In Arabidopsis, wounding
      initiates the glutamate receptor-like (GLR)-dependent propagation of membrane
      depolarizations that lead to defense gene activation. Using a vein extraction
      procedure we found pools of GLR-fusion proteins in endomembranes in phloem sieve
      elements and/or in xylem contact cells. Strikingly, only double mutants that
      eliminated GLRs from both of these spatially separated cell types strongly
      attenuated leaf-to-leaf electrical signaling. glr3.3 mutants were also
      compromised in their defense against herbivores. Since wounding is known to cause
      increases in cytosolic calcium, we monitored electrical signals and Ca2+
      transients simultaneously. This revealed that wound-induced membrane
      depolarizations in the wild-type preceded cytosolic Ca2+ maxima. The axial and
      radial distributions of calcium fluxes were differentially affected in each glr
      mutant. Resolving a debate over which cell types are necessary for electrical
      signaling between leaves, we show that phloem sieve elements and xylem contact
      cells function together in this process.

PMID- 30228126
TI  - Plant Systemic Immunity Comes Full Circle: A Positive Regulatory Loop for Defense
      Amplification.

PMID- 30228125
TI  - A MPK3/6-WRKY33-ALD1-Pipecolic Acid Regulatory Loop Contributes to Systemic
      Acquired Resistance.
AB  - Plants induce systemic acquired resistance (SAR) upon localized exposure to
      pathogens. Pipecolic acid (Pip) production via AGD2-LIKE DEFENSE RESPONSE
      PROTEIN1 (ALD1) is key for SAR establishment. Here, we report a positive feedback
      loop important for SAR induction in Arabidopsis thaliana We showed that local
      activation of the MAP kinases MPK3 and MPK6 is sufficient to trigger Pip
      production and mount SAR. Consistent with this, mutations in MPK3 or MPK6 led to
      compromised Pip accumulation upon inoculation with the bacterial pathogen
      Pseudomonas syringae pv tomato DC3000 (Pto) AvrRpt2, which triggers strong
      sustained MAPK activation. By contrast, P. syringae pv maculicola and Pto, which
      induce transient MAPK activation, trigger Pip biosynthesis and SAR independently
      of MPK3/6. ALD1 expression, Pip accumulation, and SAR were compromised in mutants
      defective in the MPK3/6-regulated transcription factor WRKY33. Chromatin
      immunoprecipitation showed that WRKY33 binds to the ALD1 promoter. We found that
      Pip triggers activation of MPK3 and MPK6 and that MAPK activation after Pto
      AvrRpt2 inoculation is compromised in wrky33 and ald1 mutants. Collectively, our
      results reveal a positive regulatory loop consisting of MPK3/MPK6, WRKY33, ALD1,
      and Pip in SAR induction and suggest the existence of distinct SAR activation
      pathways that converge at the level of Pip biosynthesis.

PMID- 30228127
TI  - Target of Rapamycin Inhibition in Chlamydomonas reinhardtii Triggers de Novo
      Amino Acid Synthesis by Enhancing Nitrogen Assimilation.
AB  - The Target of Rapamycin (TOR) kinase is a central regulator of growth and
      metabolism in all eukaryotic organisms, including animals, fungi, and plants.
      Even though the inputs and outputs of TOR signaling are well characterized for
      animals and fungi, our understanding of the upstream regulators of TOR and its
      downstream targets is still fragmentary in photosynthetic organisms. In this
      study, we employed the rapamycin-sensitive green alga Chlamydomonas reinhardtii
      to elucidate the molecular cause of the amino acid accumulation that occurs after
      rapamycin-induced inhibition of TOR. Using different growth conditions and stable
      13C- and 15N-isotope labeling, we show that this phenotype is accompanied by
      increased nitrogen (N) uptake, which is induced within minutes of TOR inhibition.
      Interestingly, this increased N influx is accompanied by increased activities of
      glutamine synthetase and glutamine oxoglutarate aminotransferase, the main N
      assimilating enzymes, which are responsible for the rise in levels of several
      amino acids, which occurs within a few minutes. Accordingly, we conclude that
      even though translation initiation and autophagy have been reported to be the
      main downstream targets of TOR, the upregulation of de novo amino acid synthesis
      seems to be one of the earliest responses induced after the inhibition of TOR in
      Chlamydomonas.

PMID- 30228129
TI  - Sarah Wells: striving for holistic care.

PMID- 30228128
TI  - Impaired bone marrow B-cell development in mice with a bronchiolitis obliterans
      model of cGVHD.
AB  - Chronic graft-versus-host disease (cGVHD) causes significant morbidity and
      mortality in patients after allogeneic bone marrow (BM) or stem cell
      transplantation (allo-SCT). Recent work has indicated that both T and B
      lymphocytes play an important role in the pathophysiology of cGVHD. Previously,
      our group showed a critical role for the germinal center response in the function
      of B cells using a bronchiolitis obliterans (BO) model of cGVHD. Here, we
      demonstrated for the first time that cGVHD is associated with severe defects in
      the generation of BM B lymphoid and uncommitted common lymphoid progenitor cells.
      We found an increase in the number of donor CD4+ T cells in the BM of mice with
      cGVHD that was negatively correlated with B-cell development and the frequency of
      osteoblasts and Prrx-1-expressing perivascular stromal cells, which are present
      in the B-cell niche. Use of anti-DR3 monoclonal antibodies to enhance the number
      of donor regulatory T cells (Tregs) in the donor T-cell inoculum ameliorated the
      pathology associated with BO in this model. This correlated with an increased
      number of endosteal osteoblastic cells and significantly improved the generation
      of B-cell precursors in the BM after allo-SCT. Our work indicates that donor
      Tregs play a critical role in preserving the generation of B-cell precursors in
      the BM after allo-SCT. Approaches to enhance the number and/or function of donor
      Tregs that do not enhance conventional T-cell activity may be important to
      decrease the incidence and severity of cGVHD in part through normal B-cell
      lymphopoiesis.

PMID- 30228130
TI  - Tar Heel Footprints in Health Care: Dr. Bob Parr Takes the Lead in Tracking
      Pollution.

PMID- 30228131
TI  - Climate Change and Public Health through the Lens of Rural, Eastern North
      Carolina.
AB  - BACKGROUND Recognizing that health outcomes are associated with climate threats
      is important and requires increased attention by health care providers and
      policymakers. The primary goal of this report is to provide information related
      to the public health threats of climate change, while identifying climate
      sensitive populations primarily in rural, Eastern North Carolina.METHODS Publicly
      available data was used to evaluate regional (eg, Eastern, Piedmont, and Western)
      and county level socio-vulnerability characteristics of population groups in
      North Carolina, including: percent of persons living in poverty, percent of non
      white persons, percent of persons under 18 years living in poverty, percent of
      elderly people living in poverty, percent of persons with a disability, and
      number of primary care physicians. One-way ANOVA was used to calculate and
      compare mean value estimates of population socio-vulnerability variables in
      Eastern North Carolina with Piedmont and Western regions.RESULTS Across all
      regional categories, the eastern part of the state had considerably higher
      averages than the state for percent of persons living in poverty (17.2%), percent
      of non-white persons (13.3%), percent of persons under 18 years old living in
      poverty (24.9%), percent of elderly people living in poverty (10.0%), and percent
      of persons with a disability (13.3%). Overwhelmingly, more counties in Eastern
      North Carolina had fewer primary care physicians (per 10,000 persons) than the
      state average (8.6 per 10,000 persons).CONCLUSION Eastern North Carolina has a
      disproportionally higher percent of population groups that are vulnerable to the
      threats of climate change. The need for health care providers to understand and
      communicate the challenges faced by rural, vulnerable population groups is of
      great public health importance. Communicating these health risks to policy makers
      is of equal importance.

PMID- 30228132
TI  - Mortality and Health Outcomes in North Carolina Communities Located in Close
      Proximity to Hog Concentrated Animal Feeding Operations.
AB  - BACKGROUND Life expectancy in southeastern North Carolina communities located in
      an area with multiple concentrated animal feeding operations (CAFOs) after
      adjusting for socioeconomic factors remains low. We hypothesized that poor health
      outcomes in this region may be due to converging demographic, socioeconomic,
      behavioral, and access-to-care factors and are influenced by the presence of hog
      CAFOs.METHODS We studied mortality, hospital admissions, and emergency department
      (ED) usage for health conditions potentially associated with hog CAFOs-anemia,
      kidney disease, infectious diseases, and low birth weight (LBW)-in North Carolina
      communities located in zip codes with hog CAFOs (Study group 1), in zip codes
      with > 215hogs/km2 (Study group 2), and without hog CAFOs (Control group). We
      compared cause-specific age-adjusted rates, the odds ratios (ORs) of events in
      multivariable analyses (adjusted for 6 co-factors), and the changes of ORs
      relative to the distance to hog CAFOs.RESULTS Residents from Study groups 1 and 2
      had higher rates of all-cause mortality, infant mortality, mortality of patients
      with multimorbidity, mortality from anemia, kidney disease, tuberculosis, and
      septicemia, and higher rates of ED visits and hospital admissions for LBW infants
      than the residents in the Control group. In zip codes with > 215hogs/km2,
      mortality ORs were 1.50 for anemia (P < 0.0001), 1.31 for kidney disease (P <
      0.0001), 2.30 for septicemia (P < 0.0001), and 2.22 for tuberculosis (P =
      0.0061).LIMITATIONS This study included a lack of individual measurements on
      environmental contaminants, biomarkers of exposures and co-factors, and
      differences in residential and occupational locations.CONCLUSION North Carolina
      communities located near hog CAFOs had higher all-cause and infant mortality,
      mortality due to anemia, kidney disease, tuberculosis, septicemia, and higher
      hospital admissions/ED visits of LBW infants. Although not establishing causality
      with exposures from hog CAFOs, our findings support the need for future studies
      to determine factors that influence these outcomes, as well as the need to
      improve screening and diagnostic strategies for these diseases in North Carolina
      communities adjacent to hog CAFOs.

PMID- 30228134
TI  - Going (Way) Back to the Basics.

PMID- 30228133
TI  - The Impact of Coal-Powered Electrical Plants and Coal Ash Impoundments on the
      Health of Residential Communities.
AB  - BACKGROUND In North Carolina, coal-burning power plants remain the major source
      of electrical production. Coal burning generates coal ash that is stored in
      landfills and slurry ponds that are often located near residential communities,
      signifying high potential for environmental contamination and increasing health
      risks. We reviewed the literature on potential health effects of coal-burning
      plants to summarize current knowledge on health risks.METHODS We searched English
      language publications issued between January 1, 1987, and December 31, 2017, on
      PubMed and Google Scholar.RESULTS The algorithm of identification, screening,
      eligibility, and inclusion/exclusion we used provided 113 peer-reviewed
      publications selected for the review. Over the past 30 years, scientists reported
      that the people living in close proximity to coal-fired plants had higher rates
      of all-cause and premature mortality, increased risk of respiratory disease and
      lung cancer, cardiovascular disease, poorer child health, and higher infant
      mortality. The elevated health risk was associated with exposure to air
      pollutants from the power plant emissions and to a spectrum of heavy metals and
      radioactive isotopes in coal ash.CONCLUSION In North Carolina, further studies
      are required to profile the severity of the cumulative impacts of multiple air,
      water, and soil contaminants related to coal-burning power plants and coal ash
      impoundments on human health and the environment. Prioritized study directions on
      evaluation of health impacts of coal-burning power plants in North Carolina are
      suggested.

PMID- 30228135
TI  - Health and the Environment in North Carolina.
AB  - Environmental impacts on health are usually discussed from a global perspective.
      However, this issue of the North Carolina Medical Journal focuses on studies of
      health outcomes in North Carolina caused by local air and water pollution. While
      some people are clearly at increased risk, environmental threats to health
      ultimately impact all of us.

PMID- 30228136
TI  - Ambient Air Quality and Cardiovascular Health: Translation of Environmental
      Research for Public Health and Clinical Care.
AB  - Air pollution is intuitively associated with respiratory effects, but evidence
      has emerged over the past few decades that the cardiovascular effects of air
      pollution can be much more adverse and represent a greater public health burden.
      In this article, we present background on the sources, exposures, and health
      effects of air pollution and discuss the potential for intervention strategies in
      the health care system to help reduce individual and population exposure and the
      attendant risk from the cardiovascular effects of air pollution.

PMID- 30228137
TI  - The Unexpected Health Effects of Air Pollution.

PMID- 30228138
TI  - Safeguarding Children's Health: Time to Enact a Health-Based Standard and
      Comprehensive Testing, Mitigation, and Communication Protocol for Lead in
      Drinking Water.
AB  - Lead was a known toxin before the Roman Empire, yet exposure remains a public
      health concern today. Although there is no safe lead exposure level, a health
      based drinking water standard has not been established. The Clean Water for
      Carolina Kids Study highlights the need for a health-based standard.

PMID- 30228139
TI  - Emerging Contaminants and Environmental Health.

PMID- 30228140
TI  - On the Front Lines of Climate Health Effects in North Carolina.
AB  - Populations across the United States are vulnerable to- and experiencing health
      effects from-climate change, and North Carolina is no exception. Health
      professionals are vital when it comes to identifying and treating such impacts,
      as well as serving as trusted authorities in educating and protecting communities
      against climate health threats.

PMID- 30228141
TI  - Heat Exposure and Health Impacts in North Carolina.

PMID- 30228142
TI  - Connecting Environmental Justice and Community Health: Effects of Hog Production
      in North Carolina.
AB  - Environmental justice means equal access to a healthful environment for all. In
      North Carolina, many sources of pollution disproportionately affect low-income
      communities and communities of color. Clinicians who recognize effects of
      environmental injustices can improve patient care and community health. As an
      example, we present the effects of industrial-scale hog operations in North
      Carolina.

PMID- 30228143
TI  - The Health Impacts of Environmental Policy: The North Carolina Clean Smokestacks
      Act.
AB  - The North Carolina Clean Smokestacks Act and related policies led to substantial
      decreases of emitted air pollutants from coal-fired power plants. Improved air
      quality was associated with statewide improvements in respiratory,
      cardiovascular, and cerebrovascular health in North Carolina. The effectiveness
      of environmental policies can be monitored for impact on both environmental and
      health outcomes.

PMID- 30228144
TI  - Clean Construction Practices at Hospitals Improve Public Health.
AB  - Diesel exhaust has been linked to numerous health issues, especially for people
      with respiratory and cardiovascular conditions. The Clean Construction
      Partnership encourages health systems to use low-emission construction equipment
      and reduce idling at their construction sites. Every dollar spent on reducing
      diesel pollution results in $13 in public health benefits [1].

PMID- 30228145
TI  - Philanthropy Profile: Protecting North Carolina's Health by Investing in a
      Healthy Environment.

PMID- 30228146
TI  - Running the Numbers: Trends in Lead Poisoning Prevention Data for Children Aged <
      6 Years in North Carolina.

PMID- 30228147
TI  - Naloxone-Prescribing Practices: A Missed Opportunity.

PMID- 30228148
TI  - David Oliver: Rosy retrospection, nostalgia, and the NHS.

PMID- 30228149
TI  - Child vaccination rates drop in England as MMR uptake falls for fourth year.

PMID- 30228151
TI  - Kidney Transplantation Rates of Veterans Administration-Listed Patients Compared
      with Rates of Patients on Nonveteran Lists.

PMID- 30228152
TI  - Media distorts findings of study on alcohol consumption and dementia risk.

PMID- 30228150
TI  - A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan.
AB  - In the past, the treatment of autosomal dominant polycystic kidney disease
      (ADPKD) has been limited to the management of its symptoms and complications.
      Recently, the US Food and Drug Administration (FDA) approved tolvaptan as the
      first drug treatment to slow kidney function decline in adults at risk of rapidly
      progressing ADPKD. Full prescribing information approved by the FDA provides
      helpful guidelines but does not address practical questions that are being raised
      by nephrologists, internists, and general practitioners taking care of patients
      with ADPKD, and by the patients themselves. In this review, we provide practical
      guidance and discuss steps that require consideration before and after
      prescribing tolvaptan to patients with ADPKD to ensure that this treatment is
      implemented safely and effectively. These steps include confirmation of
      diagnosis; identification of rapidly progressive disease; implementation of basic
      renal protective measures; counseling of patients on potential benefits and
      harms; exclusions to use; education of patients on aquaresis and its expected
      consequences; initiation, titration, and optimization of tolvaptan treatment;
      prevention of aquaresis-related complications; evaluation and management of liver
      enzyme elevations; and monitoring of treatment efficacy. Our recommendations are
      made on the basis of published evidence and our collective experiences during the
      randomized, clinical trials and open-label extension studies of tolvaptan in
      ADPKD.

PMID- 30228153
TI  - Circulating Growth and Sex Hormone Levels and Breast Tissue Composition in Young
      Nulliparous Women.
AB  - BACKGROUND: Endogenous hormones are associated with breast cancer risk, but
      little is known about their role on breast tissue composition, a strong risk
      predictor. This study aims to investigate the relationship between growth and sex
      hormone levels and breast tissue composition in young nulliparous women. METHODS:
      A cross-sectional study of 415 young (age ~21.5 years) nulliparous women from an
      English prebirth cohort underwent a MRI examination of their breasts to estimate
      percent-water (a proxy for mammographic percent density) and provided a blood
      sample to measure plasma levels of growth factors (insulin-like growth factor-I,
      insulin-like growth factor-II, insulin growth factor-binding protein-3, growth
      hormone) and, if not on hormonal contraception (n = 117) sex hormones
      (dehydroepiandrosterone, androstenedione, testosterone, estrone, estadiol, sex
      hormone-binding globulin, prolactin). Testosterone (n = 330) and sex hormone
      binding globulin (n = 318) were also measured at age 15.5 years. Regression
      models were used to estimate the relative difference (RD) in percent-water
      associated with one SD increment in hormone levels. RESULTS: Estradiol at age
      21.5 and sex hormone-binding globulin at age 21.5 were positively associated with
      body mass index (BMI)-adjusted percent-water [RD (95% confidence interval (CI)):
      3% (0%-7%) and 3% (1%-5%), respectively]. There was a positive nonlinear
      association between androstenedione at age 21.5 and percent-water. Insulin-like
      growth factor-I and growth hormone at age 21.5 were also positively associated
      with BMI-adjusted percent-water [RD (95% CI): 2% (0%-4%) and 4% (1%-7%),
      respectively]. CONCLUSIONS: The findings suggest that endogenous hormones affect
      breast tissue composition in young nulliparous women. IMPACT: The well
      established associations of childhood growth and development with breast cancer
      risk may be partly mediated by the role of endogenous hormones on breast tissue
      composition.

PMID- 30228154
TI  - Prognostic Role of Circulating Exosomal miR-425-3p for the Response of NSCLC to
      Platinum-Based Chemotherapy.
AB  - Background: Platinum-based doublets with a third-generation agent are the
      recommended option for many patients with non-small cell lung cancer (NSCLC) with
      no contraindications to platinum compounds. Unfortunately, the clinical
      effectiveness of such chemotherapy is limited by intrinsic or acquired
      resistance.Methods: Circulating exosomal miRNAs were isolated and used to perform
      HiSeq deep-sequencing analyses on serum pool samples from platinum-resistant or
      platinum-sensitive patients, and six exosomal miRNAs were further validated for
      their predictive utility by qRT-PCR in 170 serum samples of patients with
      advanced NSCLC. Gain- and loss-of-function experiments clarified the
      responsiveness regulating role of the clinically relevant miRNA. IHC analyses
      were performed to evaluate the association between basal autophagy in lung cancer
      tissues and responsiveness in 203 patients with NSCLC receiving platinum-based
      chemotherapy.Results: Six circulating exosomal miRNAs (miR-425-3p, miR-1273h, miR
      4755-5p, miR-9-5p, miR-146a-5p, and miR-215-5p) were found to be differentially
      expressed with the largest fold change in platinum-resistant patients compared
      with platinum-sensitive patients. High miR-425-3p proved to be a potent
      predictive biomarker for low responsiveness and poor progression-free survival
      (PFS). Mechanistically, miR-425-3p upregulated the autophagic levels via
      targeting AKT1, leading to the decrease in therapeutic response. Concordantly,
      high levels of basal autophagy in lung cancer tissues correlate with low
      responsiveness in patients with NSCLC within the early and advanced disease
      stages.Conclusions: Our study highlights circulating exosomal miR-425-3p as a
      potential biomarker for improved predictions of the clinical response to platinum
      based chemotherapy in patients with NSCLC.Impact: This study provides the first
      evidence that miR-425-3p in NSCLC patient-derived exosomes can be a marker for
      predicating the clinical response to platinum-based chemotherapy.

PMID- 30228155
TI  - Uptake of elective laparoscopic colectomy for colon cancer in Canada from 2004/05
      to 2014/15: a descriptive analysis.
AB  - BACKGROUND: Evidence from randomized controlled trials published since 2004 shows
      that elective laparoscopic colectomy for colon cancer improves short-term
      postoperative outcomes with equivalent oncologic outcomes compared to open
      colectomy. The objective of this study was to examine the uptake of elective
      laparoscopic colectomy in Canada and compare its use among Canadian provinces.
      METHODS: In this descriptive analysis, we identified from hospital discharge
      abstracts all patients in the Canadian provinces (except Quebec) who underwent
      elective colectomy for colon cancer between 2004/05 and 2014/15. We compared
      temporal changes in the proportion of patients who underwent laparoscopic
      colectomy or open colectomy among provinces using logistic regression. RESULTS:
      Of 63 504 patients who underwent elective colectomy between 2004/05 and 2014/15,
      19 691 (31.0%) underwent laparoscopic colectomy. The annual proportion of
      patients who underwent laparoscopic colectomy increased from 9.2% in 2004/05 to
      51.5% in 2014/15 (mean annual percent increase 4.2%). There were significant
      differences between provinces in the overall proportion of patients who underwent
      laparoscopic colectomy (p < 0.001), ranging from 7.6% in Newfoundland and
      Labrador to 36.9% in Ontario. By 2014/15, most colectomy procedures were
      performed laparoscopically in 3 provinces; British Columbia (60.2%), Ontario
      (59.4%) and Alberta (53.1%). In addition to year and province, urban residence,
      younger age, female sex, fewer medical comorbidities, high surgeon volume, high
      hospital volume and right-sided tumours were significantly associated with
      increased likelihood of laparoscopic colectomy. INTERPRETATION: Although the use
      of laparoscopic colectomy increased rapidly between 2004/05 and 2014/15 in
      Canada, substantial interprovincial variation exists. Further knowledge
      translation strategies are needed to ensure equal access to laparoscopic
      colectomy for all Canadians.

PMID- 30228156
TI  - Limits to sustained energy intake. XXIX. The case of the golden hamster
      (Mesocricetus auratus).
AB  - Golden hamster females have the shortest known gestation period among placental
      mammals, and at the same time raise very large litters of up to 16 offspring,
      which are born in a naked and blind state and are only able to pick up food from
      days 12 to 14 onwards. We quantified energy metabolism and milk production in
      female golden hamsters raising offspring under cold (8 degrees C), normal (22
      degrees C) and hot (30 degrees C) ambient temperature conditions. We monitored
      energy intake, subcutaneous body temperature, daily energy expenditure, litter
      size and pup masses over the course of lactation. Our results show that, in line
      with the concept of heat dissipation limitation, female golden hamsters had the
      largest energy intake under the coldest conditions and a significantly lower
      intake at 30 degrees C (partial for influence of ambient temperature: F
      2,403=5.6; P=0.004). Metabolisable energy intake as well as milk energy output
      showed the same pattern and were significantly different between the temperatures
      (partial for milk energy production: F 1,40=86.4; P<0.0001), with consistently
      higher subcutaneous temperatures in the reproductive females (F 1,813=36.77;
      P<0.0001) compared with baseline females. These data suggest that raising
      offspring in golden hamsters comes at the cost of producing large amounts of body
      heat up to a level constraining energy intake, similar to that observed in some
      laboratory mice. Notably, we observed that females seemed to adjust litter size
      according to their milk production, with the smallest litters (3.4+/-0.7 pups)
      being raised by hot-exposed mothers. Future research is needed to unravel the
      mechanism by which females assess their own milk production capabilities and how
      this may be linked to litter size at different ambient temperatures. Golden
      hamsters reach 8-10 times resting metabolic rate when raising offspring under
      cold conditions, which is compatible with the findings from laboratory mice and
      other rodents.

PMID- 30228157
TI  - PreB cells are moving on.
AB  - In this issue of JEM, Fistonich et al. (https://doi.org/10.1084/jem.20180778)
      address how the bone marrow microenvironment supports diverse lineages through
      multiple developmental stages. Differential motility between pro- and preB cells
      results in differential IL-7 exposure, and, intriguingly, stromal cells respond
      to abnormal B cells by reducing Il7.

PMID- 30228159
TI  - Offer histopathology trainees "golden hellos" to bolster numbers, says college.

PMID- 30228158
TI  - Pumping blood with self-reliance and cooperation.
AB  - In this issue of JEM, Singhal et al. (https://doi.org/10.1084/jem.20180008)
      explore the cellular mechanisms involved in endothelial cell regeneration in the
      liver. Using a combination of myeloablative and nonmyeloablative approaches, the
      authors found that repair of the endothelium is mediated by endothelial cells
      themselves, but when injured, endothelial cells enlist myeloid counterparts that
      aid in vascular repair.

PMID- 30228160
TI  - Tatsushi Igaki: Flying up the research summits.
AB  - Igaki explores how cell-cell communication directs tissue and tumor development.

PMID- 30228163
TI  - Donor-funded research: permissible, not perfect.
AB  - Donor-funded research is research funded by private donors in exchange for
      research-related benefits, such as trial participation or access to the trial
      intervention. This has been pejoratively referred to as 'pay to play' research,
      and criticised as unethical. We outline three models of donor-funded research,
      and argue for their permissibility on the grounds of personal liberty, their
      capacity to facilitate otherwise unfunded health research and their consistency
      with current ethical standards for research. We defend this argument against
      objections that donor-funded research is wrongly exploitative, unfair and
      undermines the public good of medical research. Our conclusion is that, like all
      human subjects research, donor-funded research should be regulated via standard
      health research legislation/guidelines and undergo Research Ethics
      Committee/Institutional Review Board and scientific peer-review. We expect that,
      measured against these standards, some donor-funded research would be acceptable.

PMID- 30228161
TI  - Cargo regulates clathrin-coated pit invagination via clathrin light chain
      phosphorylation.
AB  - Clathrin light chains (CLCs) control selective uptake of a range of G protein
      coupled receptors (GPCRs), although the mechanism by which this occurs has
      remained elusive thus far. In particular, site-specific phosphorylation of CLCb
      controls the uptake of the purinergic GPCR P2Y12, but it is dispensable for the
      constitutive uptake of the transferrin receptor (TfR). We demonstrate that
      phosphorylation of CLCb is required for the maturation of clathrin-coated pits
      (CCPs) through the transition of flat lattices into invaginated buds. This
      transition is dependent on efficient clathrin exchange regulated by CLCb
      phosphorylation and mediated through auxilin. Strikingly, this rearrangement is
      required for the uptake of P2Y12 but not TfR. These findings link auxilin
      mediated clathrin exchange to early stages of CCP invagination in a cargo
      specific manner. This supports a model in which CCPs invaginate with variable
      modes of curvature depending on the cargo they incorporate.

PMID- 30228164
TI  - Rethinking gender: The nonbinary approach.

PMID- 30228162
TI  - Occluding junctions as novel regulators of tissue mechanics during wound repair.
AB  - In epithelial tissues, cells tightly connect to each other through cell-cell
      junctions, but they also present the remarkable capacity of reorganizing
      themselves without compromising tissue integrity. Upon injury, simple epithelia
      efficiently resolve small lesions through the action of actin cytoskeleton
      contractile structures at the wound edge and cellular rearrangements. However,
      the underlying mechanisms and how they cooperate are still poorly understood. In
      this study, we combine live imaging and theoretical modeling to reveal a novel
      and indispensable role for occluding junctions (OJs) in this process. We
      demonstrate that OJ loss of function leads to defects in wound-closure dynamics:
      instead of contracting, wounds dramatically increase their area. OJ mutants
      exhibit phenotypes in cell shape, cellular rearrangements, and mechanical
      properties as well as in actin cytoskeleton dynamics at the wound edge. We
      propose that OJs are essential for wound closure by impacting on epithelial
      mechanics at the tissue level, which in turn is crucial for correct regulation of
      the cellular events occurring at the wound edge.

PMID- 30228165
TI  - Defective DNA repair in hereditary ovarian cancers: Implications for therapy.
AB  - PURPOSE: The role of mutated DNA repair pathways in hereditary ovarian cancer
      (OC) and the clinical basis for the use of poly(ADP-ribose) polymerase (PARP)
      enzyme inhibitors and an immune checkpoint inhibitor as novel targeted therapies
      in the treatment of certain OC subtypes are reviewed. SUMMARY: OC is the most
      lethal of all gynecologic malignancies and encompasses a highly diverse
      collection of cancers. Hereditary OCs are a unique subtype of OC encompassing up
      to 24% of all OCs, including cancers driven by germline mutations of the BRCA1 or
      BRCA2 genes, mutations associated with Fanconi anemia (FA), BRCAness germline
      mutations, and Lynch syndrome. With an increasing wealth of genomic data
      available in cancer research, a common thread of defective DNA repair pathways as
      a primary driver of hereditary OCs has emerged. OCs driven by BRCA1/2, FA
      associated, and BRCAness germline mutations have a demonstrated sensitivity to
      PARP inhibitors due to underlying deficiencies in DNA homologous recombination;
      however, clinical responses are often partial and highly dependent on platinum
      sensitivity. Additionally, the immune checkpoint inhibitor pembrolizumab is
      indicated for certain metastatic solid tumors characterized by microsatellite
      instability, a distinguishing feature highly associated with DNA mismatch repair
      deficiency in Lynch syndrome-associated cancers, including some OCs. CONCLUSION:
      In hereditary OC syndromes, mutations in DNA repair pathways form the clinical
      basis for the use of PARP inhibitors and an immune checkpoint inhibitor as novel
      targeted therapies.

PMID- 30228167
TI  - Government is urged to scrap visa cap for all foreign doctors after Brexit.

PMID- 30228166
TI  - Pharmacy resident involvement in prior-authorization drug request adjudication.
AB  - PURPOSE: Results of a study to determine economic outcomes of pharmacy residents'
      involvement in prior-authorization drug request (PADR) adjudication within a
      Veterans Affairs (VA) healthcare system are reported. METHODS: A retrospective
      review was conducted to identify PADRs adjudicated by pharmacy residents under a
      preceptor's supervision during the 2015-16 residency year. Only PADRs that were
      not approved as submitted (i.e., only those requiring formulary intervention) and
      that met other inclusion criteria were included in the analysis. Prior
      authorization requests and adjudication decisions were characterized, and cost
      savings resulting from those decisions were calculated. RESULTS: Of the total of
      752 PADRs adjudicated by 6 pharmacy residents during the study period, 42 met the
      inclusion criteria. About 90% of included PADRs were categorized as general
      medicine requests, and 9.5% were for oncology medications. The most common
      rationale for PADR nonapproval (cited in 60% of requests) was the availability of
      a preferred formulary alternative; the remainder of nonapprovals were due to
      medication safety concerns (e.g., contraindication to therapy, drug interaction
      potential, likelihood of adverse drug event resulting in patient harm, history of
      allergy to requested medication). Resident adjudication of PADRs resulted in
      total direct cost savings of $169,877.53 over the 12-month period, a mean of
      $4,044.70 per request. CONCLUSION: Pharmacy residents' involvement in
      adjudicating PADRs at a VA healthcare system resulted in substantial cost savings
      over the course of the residency year.

PMID- 30228168
TI  - Alcohol Use and Alcohol-Interactive Medications Among Medically Vulnerable Youth.
AB  - BACKGROUND AND OBJECTIVES: Despite their medical vulnerability, youth with
      chronic medical conditions (YCMCs) drink at levels commensurate with healthy
      youth. However, information about the prevalence of alcohol use among YCMCs who
      take alcohol-interactive (AI) medications is scant. To address gaps and inform
      interventions, we quantified simultaneous exposure to alcohol use and AI
      medications among YCMCs, hypothesizing that AI exposure would be associated with
      lower alcohol consumption and mediated by perceptions of alcohol-medication
      interference. METHODS: Adolescents with type 1 diabetes, juvenile idiopathic
      arthritis, moderate persistent asthma, cystic fibrosis, attention
      deficit/hyperactivity disorder, or inflammatory bowel disease completed an
      electronic survey. We measured the prevalence of exposure to AI medications and
      the associations with past-year alcohol use as well as binge drinking and total
      consumption volume in the past 3 months using multivariate regression to estimate
      the odds of alcohol use given AI medication exposure and perceptions of
      interference. RESULTS: Of 396 youth, 86.4% were on AI medications, of whom, 35.4%
      reported past-year alcohol use (46.3% among those who were not on AI
      medications). AI medication use was associated with 43% lower odds of past-year
      alcohol use (adjusted odds ratio: 0.57; 95% confidence interval: 0.39-0.85) and
      lower total consumption (beta = -.43; SE = 0.11; P < .001). Perceptions of
      alcohol-medication interference partially mediated the relationship between AI
      medication exposure and past-year alcohol use (Sobel test P = .05). CONCLUSIONS:
      Many YCMCs reported using alcohol; however, drinking was less likely among those
      who were taking AI medications. Perceptions about alcohol-medication interference
      mediated the association between drinking and AI medication exposure, suggesting
      the potential salience of interventions that emphasize alcohol-related risks.

PMID- 30228169
TI  - OpenNotes: Toward a Participatory Pediatric Health System.

PMID- 30228170
TI  - Education from other sports medicine journals #11.

PMID- 30228171
TI  - Do female elite athletes experience more complicated childbirth than non
      athletes? A case-control study.
AB  - OBJECTIVE: Previous studies have suggested that female athletes might be at
      higher risk of experiencing complications such as caesarean sections and perineal
      tears during labour than non-athletes. Our aim was to study delivery outcomes,
      including emergency caesarean section rates, length of the first and second
      stages of labour and severe perineal tears, in first-time pregnant elite athletes
      compared with non-athletes. METHODS: This is a retrospective case-control study
      comparing birth outcomes of primiparous female elite athletes engaging in high
      impact and low-impact sports compared with non-athletic controls. The athletes
      had prior to birth competed at a national team level or equivalent. Participant
      characteristics and frequency of training for at least 3 years before a first
      pregnancy were collected via a self-administered questionnaire. Information on
      delivery outcome was retrieved from the Icelandic Medical Birth Registry.
      RESULTS: In total, 248 participated, 118 controls, 41 low-impact and 89 high
      impact elite athletes. No significant differences were found between the groups
      with regard to incidence of emergency caesarean section or length of the first
      and second stages of labour. The incidence of third-degree to fourth-degree
      perineal tears was significantly higher (23.7%) among low-impact athletes than in
      the high-impact group (5.1%, p=0.01), but no significant differences were seen
      when the athletes were compared with the controls (12%; p=0.09 for low-impact and
      p=0.12 for high-impact athletes). CONCLUSION: Participation in competitive sports
      at the elite level was not related to adverse delivery outcome, including length
      of labour, the need for caesarean section during delivery and severe perineal
      tears.

PMID- 30228172
TI  - Comprehensive Phenotypic Characterization of Human Invasive Lobular Carcinoma
      Cell Lines in 2D and 3D Cultures.
AB  - Invasive lobular carcinoma (ILC) is the second most common subtype of breast
      cancer following invasive ductal carcinoma (IDC) and characterized by the loss of
      E-cadherin-mediated adherens junctions. Despite displaying unique histologic and
      clinical features, ILC still remains a chronically understudied disease, with
      limited knowledge gleaned from available laboratory research models. Here we
      report a comprehensive 2D and 3D phenotypic characterization of four estrogen
      receptor-positive human ILC cell lines: MDA-MB-134, SUM44, MDA-MB-330, and BCK4.
      Compared with the IDC cell lines MCF7, T47D, and MDA-MB-231, ultra-low attachment
      culture conditions revealed remarkable anchorage independence unique to ILC
      cells, a feature not evident in soft-agar gels. Three-dimensional Collagen I and
      Matrigel culture indicated a generally loose morphology for ILC cell lines, which
      exhibited differing preferences for adhesion to extracellular matrix proteins in
      2D. Furthermore, ILC cells were limited in their ability to migrate and invade in
      wound-scratch and transwell assays, with the exception of haptotaxis to Collagen
      I. Transcriptional comparison of these cell lines confirmed the decreased cell
      proliferation and E-cadherin-mediated intercellular junctions in ILC while
      uncovering the induction of novel pathways related to cyclic nucleotide
      phosphodiesterase activity, ion channels, drug metabolism, and alternative cell
      adhesion molecules such as N-cadherin, some of which were differentially
      regulated in ILC versus IDC tumors. Altogether, these studies provide an
      invaluable resource for the breast cancer research community and facilitate
      further functional discoveries toward understanding ILC, identifying novel drug
      targets, and ultimately improving the outcome of patients with ILC.Significance:
      These findings provide the breast cancer research community with a comprehensive
      assessment of human invasive lobular carcinoma (ILC) cell line signaling and
      behavior in various culture conditions, aiding future endeavors to develop
      therapies and to ultimately improve survival in patients with ILC. Cancer Res;
      78(21); 6209-22. (c)2018 AACR.

PMID- 30228173
TI  - Preclinical Evaluation of the Hsp70 Peptide Tracer TPP-PEG24-DFO[89Zr] for Tumor
      Specific PET/CT Imaging.
AB  - High precision in vivo PET/CT imaging of solid tumors improves diagnostic
      credibility and clinical outcome of patients. An epitope of the oligomerization
      domain of Hsp70 is exclusively exposed on the membrane of a large variety of
      tumor types, but not on normal cells, and thus provides a universal tumor
      specific target. Here we developed a novel PET tracer TPP-PEG24-DFO[89Zr] based
      on the tumor cell-penetrating peptide probe TPP, which specifically recognizes
      membrane Hsp70 (mHsp70) on tumor cells. The implemented PEG24 moiety supported
      tracer stability and improved biodistribution characteristics in vivo The K d of
      the tracer ranged in the low nanomolar range (18.9 +/- 11.3 nmol/L). Fluorescein
      isothiocyanate (FITC)-labeled derivatives TPP-[FITC] and TPP-PEG24-[FITC]
      revealed comparable and specific binding to mHsp70-positive 4T1, 4T1+, a
      derivative of the 4T1 cell line sorted for high Hsp70 expression, and CT26 tumor
      cells, but not to mHsp70-negative normal fibroblasts. The rapid internalization
      kinetics of mHsp70 into the cytosol and the favorable biodistribution of the
      peptide-based tracer TPP-PEG24-DFO[89Zr] in vivo enabled a tumor-specific
      accumulation with a high tumor-to-background contrast and renal body clearance.
      The tumor-specific enrichment of the tracer in 4T1+ (6.2 +/- 1.1%ID/g), 4T1 (4.3
      +/- 0.7%ID/g), and CT26 (2.6 +/- 0.6%ID/g) mouse tumors with very high, high, and
      intermediate mHsp70 densities, respectively, reflected mHsp70 expression profiles
      of the different tumor types, whereas benign mHsp70-negative fibroblastic
      hyperplasia showed no tracer accumulation (0.2 +/- 0.03%ID/g). The ability of our
      chemically optimized peptide-based tracer TPP-PEG24-DFO[89Zr] to detect mHsp70 in
      vivo suggests its broad applicability in targeting and imaging with high
      specificity for any tumor type that exhibits surface expression of
      Hsp70.Significance: A novel peptide-based PET tracer against the oligomerization
      domain of Hsp70 has potential for universal tumor-specific imaging in vivo across
      many tumor type. Cancer Res; 78(21); 6268-81. (c)2018 AACR.

PMID- 30228174
TI  - Hypertension and consequent mortality risk in China.

PMID- 30228175
TI  - News Feature: What's the best way to build a molecular machine?

PMID- 30228177
TI  - Growing community of artificial molecular machinists.

PMID- 30228178
TI  - Correction for Chen et al., Diverse AR-V7 cistromes in castration-resistant
      prostate cancer are governed by HoxB13.

PMID- 30228179
TI  - Intertumoral Heterogeneity in SCLC Is Influenced by the Cell Type of Origin.
AB  - The extent to which early events shape tumor evolution is largely
      uncharacterized, even though a better understanding of these early events may
      help identify key vulnerabilities in advanced tumors. Here, using genetically
      defined mouse models of small cell lung cancer (SCLC), we uncovered distinct
      metastatic programs attributable to the cell type of origin. In one model, tumors
      gain metastatic ability through amplification of the transcription factor NFIB
      and a widespread increase in chromatin accessibility, whereas in the other model,
      tumors become metastatic in the absence of NFIB-driven chromatin alterations.
      Gene-expression and chromatin accessibility analyses identify distinct mechanisms
      as well as markers predictive of metastatic progression in both groups.
      Underlying the difference between the two programs was the cell type of origin of
      the tumors, with NFIB-independent metastases arising from mature neuroendocrine
      cells. Our findings underscore the importance of the identity of cell type of
      origin in influencing tumor evolution and metastatic mechanisms.Significance: We
      show that SCLC can arise from different cell types of origin, which profoundly
      influences the eventual genetic and epigenetic changes that enable metastatic
      progression. Understanding intertumoral heterogeneity in SCLC, and across cancer
      types, may illuminate mechanisms of tumor progression and uncover how the cell
      type of origin affects tumor evolution. Cancer Discov; 8(10); 1316-31. (c)2018
      AACR. See related commentary by Pozo et al., p. 1216 This article is highlighted
      in the In This Issue feature, p. 1195.

PMID- 30228180
TI  - The long noncoding RNA GAS8-AS1 suppresses hepatocarcinogenesis by epigenetically
      activating the tumor suppressor GAS8.
AB  - Long noncoding RNAs (lncRNAs) are vital players in cancers, including
      hepatocellular carcinoma (HCC). We previously identified an lncRNA, GAS8-AS1,
      that is located in intron 2 of GAS8 However, its involvement in HCC is still
      largely unknown. In this study, we report that both GAS8-AS1 and its host gene
      GAS8 act as HCC tumor suppressors. We found that expression of GAS8-AS1 or GAS8
      is significantly decreased in HCC tissues and is associated with a poor prognosis
      among HCC patients. Interestingly, lncRNA GAS8-AS1 could promote GAS8
      transcription. We detected a CpG island in the GAS8 promoter, but lncRNA GAS8-AS1
      did not affect DNA methylation at this GAS8 promoter site. Moreover, we
      identified two GAS8-AS1-interacting proteins, mixed-lineage leukemia 1 (MLL1), a
      histone 3 Lys-4 (H3K4) methyltransferase, and its partner WD-40 repeat protein 5
      (WDR5). RNA pulldown, ChIP, and RNA immunoprecipitation assays revealed that GAS8
      AS1 is required for maintaining the GAS8 promoter in an open chromatin state by
      recruiting the MLL1/WDR5 complex and for enhancing RNA polymerase II activity and
      GAS8 transcription. Of note, GAS8-AS1-dependent GAS8 hyperactivation inhibited
      malignant transformation of hepatocytes. Our results provide important insights
      into how lncRNA GAS8-AS1 suppresses HCC development and suggest potential
      strategies for treating patients with liver cancer.

PMID- 30228181
TI  - The C-terminal GGAP motif of Hsp70 mediates substrate recognition and stress
      response in yeast.
AB  - The allosteric coupling of the highly conserved nucleotide- and substrate-binding
      domains of Hsp70 has been studied intensively. In contrast, the role of the
      disordered, highly variable C-terminal region of Hsp70 remains unclear. In many
      eukaryotic Hsp70s, the extreme C-terminal EEVD motif binds to the
      tetratricopeptide-repeat domains of Hsp70 co-chaperones. Here, we discovered that
      the TVEEVD sequence of Saccharomyces cerevisiae cytoplasmic Hsp70 (Ssa1)
      functions as a SUMO-interacting motif. A second C-terminal motif of ~15 amino
      acids between the alpha-helical lid and the extreme C terminus, previously
      identified in bacterial and eukaryotic organellar Hsp70s, is known to enhance
      chaperone function by transiently interacting with folding clients. Using
      structural analysis, interaction studies, fibril formation assays, and in vivo
      functional assays, we investigated the individual contributions of the alpha
      helical bundle and the C-terminal disordered region of Ssa1 in the inhibition of
      fibril formation of the prion protein Ure2. Our results revealed that although
      the alpha-helical bundle of the Ssa1 substrate-binding domain (SBDalpha) does not
      directly bind to Ure2, the SBDalpha enhances the ability of Hsp70 to inhibit
      fibril formation. We found that a 20-residue C-terminal motif in Ssa1, containing
      GGAP and GGAP-like tetrapeptide repeats, can directly bind to Ure2, the Hsp40 co
      chaperone Ydj1, and alpha-synuclein, but not to the SUMO-like protein SMT3 or
      BSA. Deletion or substitution of the Ssa1 GGAP motif impaired yeast cell
      tolerance to temperature and cell-wall damage stress. This study highlights that
      the C-terminal GGAP motif of Hsp70 is important for substrate recognition and
      mediation of the heat shock response.

PMID- 30228182
TI  - Redox regulation of type-I inositol trisphosphate receptors in intact mammalian
      cells.
AB  - A sensitization of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+
      release is associated with oxidative stress in multiple cell types. These effects
      are thought to be mediated by alterations in the redox state of critical thiols
      in the IP3R, but this has not been directly demonstrated in intact cells. Here,
      we utilized a combination of gel-shift assays with MPEG-maleimides and LC-MS/MS
      to monitor the redox state of recombinant IP3R1 expressed in HEK293 cells. We
      found that under basal conditions, ~5 of the 60 cysteines are oxidized in IP3R1.
      Cell treatment with 50 MUm thimerosal altered gel shifts, indicating oxidation of
      ~20 cysteines. By contrast, the shifts induced by 0.5 mm H2O2 or other oxidants
      were much smaller. Monitoring of biotin-maleimide attachment to IP3R1 by LC-MS/MS
      with 71% coverage of the receptor sequence revealed modification of two cytosolic
      (Cys-292 and Cys-1415) and two intraluminal cysteines (Cys-2496 and Cys-2533)
      under basal conditions. The thimerosal treatment modified an additional eleven
      cysteines, but only three (Cys-206, Cys-767, and Cys-1459) were consistently
      oxidized in multiple experiments. H2O2 also oxidized Cys-206 and additionally
      oxidized two residues not modified by thimerosal (Cys-214 and Cys-1397).
      Potentiation of IP3R channel function by oxidants was measured with cysteine
      variants transfected into a HEK293 IP3R triple-knockout cell line, indicating
      that the functionally relevant redox-sensitive cysteines are predominantly
      clustered within the N-terminal suppressor domain of IP3R. To our knowledge, this
      study is the first that has used proteomic methods to assess the redox state of
      individual thiols in IP3R in intact cells.

PMID- 30228183
TI  - A single residue switch reveals principles of antibody domain integrity.
AB  - Despite their importance for antibody architecture and design, the principles
      governing antibody domain stability are still not understood in sufficient
      detail. Here, to address this question, we chose a domain from the invariant part
      of IgG, the CH2 domain. We found that compared with other Ig domains, the
      isolated CH2 domain is a surprisingly unstable monomer, exhibiting a melting
      temperature of ~44  degrees C. We further show that the presence of an additional
      C-terminal lysine in a CH2 variant substantially increases the melting
      temperature by ~14  degrees C relative to CH2 WT. To explore the molecular
      mechanism of this effect, we employed biophysical approaches to probe structural
      features of CH2. The results revealed that Lys101 is key for the formation of
      three secondary structure elements: the very C-terminal beta-strand and two
      adjacent alpha-helices. We also noted that a dipole interaction between Lys101
      and the nearby alpha-helix, is important for stabilizing the CH2 architecture by
      protecting the hydrophobic core. Interestingly, this interaction between the
      alpha-helix and C-terminal charged residues is highly conserved in antibody
      domains, suggesting that it represents a general mechanism for maintaining their
      integrity. We conclude that the observed interactions involving terminal residues
      have practical applications for defining domain boundaries in the development of
      antibody therapeutics and diagnostics.

PMID- 30228184
TI  - The labile interactions of cyclic electron flow effector proteins.
AB  - The supramolecular organization of membrane proteins (MPs) is sensitive to
      environmental changes in photosynthetic organisms. Isolation of MP supercomplexes
      from the green algae Chlamydomonas reinhardtii, which are believed to contribute
      to cyclic electron flow (CEF) between the cytochrome b 6 f complex (Cyt-b 6 f)
      and photosystem I (PSI), proved difficult. We were unable to isolate a
      supercomplex containing both Cyt-b 6 f and PSI because in our hands, most of Cyt
      b 6 f did not comigrate in sucrose density gradients, even upon using chemical
      cross-linkers or amphipol substitution of detergents. Assisted by independent
      affinity purification and MS approaches, we utilized disintegrating MP assemblies
      and demonstrated that the algae-specific CEF effector proteins PETO and ANR1 are
      bona fide Cyt-b 6 f interactors, with ANR1 requiring the presence of an
      additional, presently unknown, protein. We narrowed down the Cyt-b 6 f interface,
      where PETO is loosely attached to cytochrome f and to a stromal region of subunit
      IV, which also contains phosphorylation sites for the STT7 kinase.

PMID- 30228185
TI  - The small GTPase RAB28 is required for phagocytosis of cone outer segments by the
      murine retinal pigmented epithelium.
AB  - RAB28, a member of the RAS oncogene family, is a ubiquitous, farnesylated, small
      GTPase of unknown function present in photoreceptors and the retinal pigmented
      epithelium (RPE). Nonsense mutations of the human RAB28 gene cause recessive cone
      rod dystrophy 18 (CRD18), characterized by macular hyperpigmentation, progressive
      loss of visual acuity, RPE atrophy, and severely attenuated cone and rod
      electroretinography (ERG) responses. In an attempt to elucidate the disease
      causing mechanism, we generated Rab28 -/- mice by deleting exon 3 and truncating
      RAB28 after exon 2. We found that Rab28 -/- mice recapitulate features of the
      human dystrophy (i.e. they exhibited reduced cone and rod ERG responses and
      progressive retina degeneration). Cones of Rab28 -/- mice extended their outer
      segments (OSs) to the RPE apical processes and formed enlarged, balloon-like
      distal tips before undergoing degeneration. The visual pigment content of WT and
      Rab28 -/- cones was comparable before the onset of degeneration. Cone phagosomes
      were almost absent in Rab28 -/- mice, whereas rod phagosomes displayed normal
      levels. A protein-protein interaction screen identified several RAB28-interacting
      proteins, including the prenyl-binding protein phosphodiesterase 6 delta-subunit
      (PDE6D) and voltage-gated potassium channel subfamily J member 13 (KCNJ13)
      present in the RPE apical processes. Of note, the loss of PDE6D prevented
      delivery of RAB28 to OSs. Taken together, these findings reveal that RAB28 is
      required for shedding and phagocytosis of cone OS discs.

PMID- 30228186
TI  - K-Ras Lys-42 is crucial for its signaling, cell migration, and invasion.
AB  - Ras proteins participate in multiple signal cascades, regulating crucial cellular
      processes, including cell survival, proliferation, and differentiation. We have
      previously reported that Ras proteins are modified by sumoylation and that Lys-42
      plays an important role in mediating the modification. In the current study, we
      further investigated the role of Lys-42 in regulating cellular activities of K
      Ras. Inducible expression of K-RasV12 led to the activation of downstream
      components, including c-RAF, MEK1, and extracellular signal-regulated kinases
      (ERKs), whereas expression of K-RasV12/R42 mutant compromised the activation of
      the RAF/MEK/ERK signaling axis. Expression of K-RasV12/R42 also led to reduced
      phosphorylation of several other protein kinases, including c-Jun N-terminal
      kinase (JNK), Chk2, and focal adhesion kinase (FAK). Significantly, K-RasV12/R42
      expression inhibited cellular migration and invasion in vitro in multiple cell
      lines, including transformed pancreatic cells. Given that K-Ras plays a crucial
      role in mediating oncogenesis in the pancreas, we treated transformed pancreatic
      cells of both BxPC-3 and MiaPaCa-2 with 2-D08, a small ubiquitin-like modifier
      (SUMO) E2 inhibitor. Treatment with the compound inhibited cell migration in a
      concentration-dependent manner, which was correlated with a reduced level of K
      Ras sumoylation. Moreover, 2-D08 suppressed expression of ZEB1 (a mesenchymal
      cell marker) with concomitant induction of ZO-1 (an epithelial cell marker).
      Combined, our studies strongly suggest that posttranslational modification(s),
      including sumoylation mediated by Lys-42, plays a crucial role in K-Ras
      activities in vivo.

PMID- 30228188
TI  - The structure of the deubiquitinase USP15 reveals a misaligned catalytic triad
      and an open ubiquitin-binding channel.
AB  - Ubiquitin-specific protease 15 (USP15) regulates important cellular processes,
      including transforming growth factor beta (TGF-beta) signaling, mitophagy, mRNA
      processing, and innate immune responses; however, structural information on
      USP15's catalytic domain is currently unavailable. Here, we determined crystal
      structures of the USP15 catalytic core domain, revealing a canonical USP fold,
      including a finger, palm, and thumb region. Unlike for the structure of paralog
      USP4, the catalytic triad is in an inactive configuration with the catalytic
      cysteine ~10 A apart from the catalytic histidine. This conformation is atypical,
      and a similar misaligned catalytic triad has so far been observed only for USP7,
      although USP15 and USP7 are differently regulated. Moreover, we found that the
      active-site loops are flexible, resulting in a largely open ubiquitin tail
      binding channel. Comparison of the USP15 and USP4 structures points to a possible
      activation mechanism. Sequence differences between these two USPs mainly map to
      the S1' region likely to confer specificity, whereas the S1 ubiquitin-binding
      pocket is highly conserved. Isothermal titration calorimetry monoubiquitin- and
      linear diubiquitin-binding experiments showed significant differences in their
      thermodynamic profiles, with USP15 displaying a lower affinity for monoubiquitin
      than USP4. Moreover, we report that USP15 is weakly inhibited by the
      antineoplastic agent mitoxantrone in vitro A USP15-mitoxantrone complex structure
      disclosed that the anthracenedione interacts with the S1' binding site. Our
      results reveal first insights into USP15's catalytic domain structure,
      conformational changes, differences between paralogs, and small-molecule
      interactions and establish a framework for cellular probe and inhibitor
      development.

PMID- 30228187
TI  - Complement 1q-like-3 protein inhibits insulin secretion from pancreatic beta
      cells via the cell adhesion G protein-coupled receptor BAI3.
AB  - Secreted proteins are important metabolic regulators in both healthy and disease
      states. Here, we sought to investigate the mechanism by which the secreted
      protein complement 1q-like-3 (C1ql3) regulates insulin secretion from pancreatic
      beta-cells, a key process affecting whole-body glucose metabolism. We found that
      C1ql3 predominantly inhibits exendin-4- and cAMP-stimulated insulin secretion
      from mouse and human islets. However, to a lesser extent, C1ql3 also reduced
      insulin secretion in response to KCl, the potassium channel blocker tolbutamide,
      and high glucose. Strikingly, C1ql3 did not affect insulin secretion stimulated
      by fatty acids, amino acids, or mitochondrial metabolites, either at low or
      submaximal glucose concentrations. Additionally, C1ql3 inhibited glucose
      stimulated cAMP levels, and insulin secretion stimulated by exchange protein
      directly activated by cAMP-2 and protein kinase A. These results suggest that
      C1ql3 inhibits insulin secretion primarily by regulating cAMP signaling. The cell
      adhesion G protein-coupled receptor, brain angiogenesis inhibitor-3 (BAI3), is a
      C1ql3 receptor and is expressed in beta-cells and in mouse and human islets, but
      its function in beta-cells remained unknown. We found that siRNA-mediated Bai3
      knockdown in INS1(832/13) cells increased glucose-stimulated insulin secretion.
      Furthermore, incubating the soluble C1ql3-binding fragment of the BAI3 protein
      completely blocked the inhibitory effects of C1ql3 on insulin secretion in
      response to cAMP. This suggests that BAI3 mediates the inhibitory effects of
      C1ql3 on insulin secretion from pancreatic beta-cells. These findings demonstrate
      a novel regulatory mechanism by which C1ql3/BAI3 signaling causes an impairment
      of insulin secretion from beta-cells, possibly contributing to the progression of
      type 2 diabetes in obesity.

PMID- 30228191
TI  - Archaic and alternative chaperones preserve pilin folding energy by providing
      incomplete structural information.
AB  - Adhesive pili are external component of fibrous adhesive organelles and help
      bacteria attach to biotic or abiotic surfaces. The biogenesis of adhesive pili
      via the chaperone-usher pathway (CUP) is independent of external energy sources.
      In the classical CUP, chaperones transport assembly-competent pilins in a folded
      but expanded conformation. During donor-strand exchange, pilins subsequently
      collapse, producing a tightly packed hydrophobic core and releasing the necessary
      free energy to drive fiber formation. Here, we show that pilus biogenesis in non
      classical, archaic, and alternative CUPs uses a different source of
      conformational energy. High-resolution structures of the archaic Csu-pili system
      from Acinetobacter baumannii revealed that non-classical chaperones employ a
      short donor strand motif that is insufficient to fully complement the pilin fold.
      This results in chaperone-bound pilins being trapped in a substantially unfolded
      intermediate. The exchange of this short motif with the longer donor strand from
      adjacent pilin provides the full steric information essential for folding, and
      thereby induces a large unfolded-to-folded conformational transition to drive
      assembly. Our findings may inform the development of anti-adhesion drugs
      (pilicides) to combat bacterial infections.

PMID- 30228190
TI  - Slow activation of fast mitochondrial Ca2+ uptake by cytosolic Ca2.
AB  - Mitochondrial Ca2+ uptake through the mitochondrial Ca2+ uniporter (MCU) is a
      tightly controlled process that sustains cell functions mainly by fine-tuning
      oxidative metabolism to cellular needs. The kinetics of Ca2+ fluxes across the
      mitochondrial membranes have been studied both in vitro and in vivo for many
      years, and the discovery of the molecular components of the MCU has further
      clarified that this Ca2+ uptake mechanism is based on a complex system subject to
      elaborate layers of controls. Alterations in the speed or capacity of the in-and
      out pathways can have detrimental consequences for both the organelle and the
      cell, impairing cellular metabolism and ultimately causing cell death. Here, we
      report that pretreatment of deenergized mitochondria with low-micromolar Ca2+
      concentrations for a few minutes markedly increases the speed of mitochondrial
      Ca2+ uptake upon re-addition of an oxidizable substrate. We found that this
      phenomenon is sensitive to alterations in the level of the MCU modulator proteins
      mitochondrial calcium uptake 1 (MICU1) and 2 (MICU2), and is accompanied by
      changes in the association of MICU1-MICU2 complexes with MCU. This increased Ca2+
      uptake capacity, occurring under conditions mimicking those during
      ischemia/reperfusion in vivo, could lead to a massive amount of Ca2+ entering the
      mitochondrial matrix even at relatively low levels of cytosolic Ca2+ We conclude
      that the phenomenon uncovered here represents a potential threat of mitochondrial
      Ca2+ overload to the cell.

PMID- 30228189
TI  - Thumb domains of the three epithelial Na+ channel subunits have distinct
      functions.
AB  - The epithelial Na+ channel (ENaC) possesses a large extracellular domain formed
      by a beta-strand core enclosed by three peripheral alpha-helical subdomains,
      which have been dubbed thumb, finger, and knuckle. Here we asked whether the ENaC
      thumb domains play specific roles in channel function. To this end, we examined
      the characteristics of channels lacking a thumb domain in an individual ENaC
      subunit (alpha, beta, or gamma). Removing the gamma subunit thumb domain had no
      effect on Na+ currents when expressed in Xenopus oocytes, but moderately reduced
      channel surface expression. In contrast, ENaCs lacking the alpha or beta subunit
      thumb domain exhibited significantly reduced Na+ currents along with a large
      reduction in channel surface expression. Moreover, channels lacking an alpha or
      gamma thumb domain exhibited a diminished Na+ self-inhibition response, whereas
      this response was retained in channels lacking a beta thumb domain. In turn,
      deletion of the alpha thumb domain had no effect on the degradation rate of the
      immature alpha subunit as assessed by cycloheximide chase analysis. However,
      accelerated degradation of the immature beta subunit and mature gamma subunit was
      observed when the beta or gamma thumb domain was deleted, respectively. Our
      results suggest that the thumb domains in each ENaC subunit are required for
      optimal surface expression in oocytes and that the alpha and gamma thumb domains
      both have important roles in the channel's inhibitory response to external Na+
      Our findings support the notion that the extracellular helical domains serve as
      functional modules that regulate ENaC biogenesis and activity.

PMID- 30228193
TI  - Chromobodies to Quantify Changes of Endogenous Protein Concentration in Living
      Cells.
AB  - Understanding cellular processes requires the determination of dynamic changes in
      the concentration of genetically nonmodified, endogenous proteins, which, to
      date, is commonly accomplished by end-point assays in vitro Molecular probes such
      as fluorescently labeled nanobodies (chromobodies, CBs) are powerful tools to
      visualize the dynamic subcellular localization of endogenous proteins in living
      cells. Here, we employed the dependence of intracellular levels of chromobodies
      on the amount of their endogenous antigens, a phenomenon, which we termed antigen
      mediated CB stabilization (AMCBS), for simultaneous monitoring of time-resolved
      changes in the concentration and localization of native proteins. To improve the
      dynamic range of AMCBS we generated turnover-accelerated CBs and demonstrated
      their application in visualization and quantification of fast reversible changes
      in antigen concentration upon compound treatment by quantitative live-cell
      imaging. We expect that this broadly applicable strategy will enable
      unprecedented insights into the dynamic regulation of proteins, e.g. during
      cellular signaling, cell differentiation, or upon drug action.

PMID- 30228194
TI  - A Quantitative Chemical Proteomic Strategy for Profiling Phosphoprotein
      Phosphatases from Yeast to Humans.
AB  - A "tug-of-war" between kinases and phosphatases establishes the phosphorylation
      states of proteins. While serine and threonine phosphorylation can be catalyzed
      by more than 400 protein kinases, the majority of serine and threonine
      dephosphorylation is carried out by seven phosphoprotein phosphatases (PPPs). The
      PPP family consists of protein phosphatases 1 (PP1), 2A (PP2A), 2B (PP2B), 4
      (PP4), 5 (PP5), 6 (PP6), and 7 (PP7). The imbalance in numbers between serine-
      and threonine-directed kinases and phosphatases led to the early belief that PPPs
      are unspecific and that kinases are the primary determinants of protein
      phosphorylation. However, it is now clear that PPPs achieve specificity through
      association with noncatalytic subunits to form multimeric holoenzymes, which
      expands the number of functionally distinct signaling entities to several
      hundred. Although there has been great progress in deciphering signaling by
      kinases, much less is known about phosphatases.We have developed a chemical
      proteomic strategy for the systematic interrogation of endogenous PPP catalytic
      subunits and their interacting proteins, including regulatory and scaffolding
      subunits (the "PPPome"). PP1, PP2A, PP4, PP5, and PP6 were captured using an
      immobilized, specific but nonselective PPP inhibitor microcystin-LR (MCLR),
      followed by protein identification by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) in a single analysis. Here, we combine this approach of
      phosphatase inhibitor bead profiling and mass spectrometry (PIB-MS) with label
      free and tandem mass tag (TMT) quantification to map the PPPome in human cancer
      cell lines, mouse tissues, and yeast species, through which we identify cell- and
      tissue-type-specific PPP expression patterns and discover new PPP interacting
      proteins.

PMID- 30228192
TI  - Whole-Genome Multi-omic Study of Survival in Patients with Glioblastoma
      Multiforme.
AB  - Glioblastoma multiforme (GBM) has been recognized as the most lethal type of
      malignant brain tumor. Despite efforts of the medical and research community,
      patients' survival remains extremely low. Multi-omic profiles (including DNA
      sequence, methylation and gene expression) provide rich information about the
      tumor. These profiles are likely to reveal processes that may be predictive of
      patient survival. However, the integration of multi-omic profiles, which are high
      dimensional and heterogeneous in nature, poses great challenges. The goal of this
      work was to develop models for prediction of survival of GBM patients that can
      integrate clinical information and multi-omic profiles, using multi-layered
      Bayesian regressions. We apply the methodology to data from GBM patients from The
      Cancer Genome Atlas (TCGA, n = 501) to evaluate whether integrating multi-omic
      profiles (SNP-genotypes, methylation, copy number variants and gene expression)
      with clinical information (demographics as well as treatments) leads to an
      improved ability to predict patient survival. The proposed Bayesian models were
      used to estimate the proportion of variance explained by clinical covariates and
      omics and to evaluate prediction accuracy in cross validation (using the area
      under the Receiver Operating Characteristic curve, AUC). Among clinical and
      demographic covariates, age (AUC = 0.664) and the use of temozolomide (AUC =
      0.606) were the most predictive of survival. Among omics, methylation (AUC =
      0.623) and gene expression (AUC = 0.593) were more predictive than either SNP
      (AUC = 0.539) or CNV (AUC = 0.547). While there was a clear association between
      age and methylation, the integration of age, the use of temozolomide, and either
      gene expression or methylation led to a substantial increase in AUC in cross
      validaton (AUC = 0.718). Finally, among the genes whose methylation was higher in
      aging brains, we observed a higher enrichment of these genes being also
      differentially methylated in cancer.

PMID- 30228196
TI  - US agency changes alcohol advice after doctor complains.

PMID- 30228195
TI  - Vascular access training for REBOA placement: a feasibility study in a live
      tissue-simulator hybrid porcine model.
AB  - BACKGROUND: The use of resuscitative endovascular balloon occlusion of the aorta
      (REBOA) in patients with severe haemorrhagic shock is increasing. Obtaining
      vascular access is a necessary prerequisite for REBOA placement in these
      situations. METHODS: During the EVTM workshop (September 2017, Orebro, Sweden),
      21 individuals participated in this study, 16 participants and five instructors.
      A formalised curriculum was constructed including basic anatomy of the femoral
      region and basic training in access materials for REBOA placement in zone 1. Key
      skills: (1) preparation of endovascular toolkit, (2) achieving vascular access in
      the model and (3) bleeding control with REBOA. Scoring ranged from 0 to 5 for non
      anatomical skills. Identification of anatomical structures was either sufficient
      (score=1) or insufficient (score=0). Five consultants performed a second
      identical procedure as a post test. RESULTS: Consultants had significantly better
      overall technical skills in comparison with residents (p=0.005), while
      understanding of surgical anatomy showed no difference. Procedure times differed
      significantly (p<0.01), with residents having a median procedure time of 3 min
      and 24 s, consultants 2:33 and instructors 1:09. CONCLUSION: This comprehensive
      training model using a live tissue-simulator hybrid porcine model can be used for
      femoral access and REBOA placement training in medical personnel with different
      prior training levels. Higher levels of training are associated with faster
      procedure times. Further research in open and percutaneous access training is
      necessary to simulate real-life situations. This training method can be used in a
      multistep training programme, in combination with realistic moulage and perfused
      cadaver models.

PMID- 30228198
TI  - Evidence-based patient/public voice: a patient and public involvement audit in
      the field of sexual health.
AB  - BACKGROUND: The National Health Institute constitution enshrines the central role
      of patient and public involvement (PPI) in order to place patients at the heart
      of the NHS. The sexual health field presents unique challenges for PPI in the
      tension between current PPI practice versus the need for confidentiality/feelings
      of shame/stigma. However, there is little evidence around the goals, evaluation
      measures or theoretical underpinnings of PPI. OBJECTIVES: In order to improve
      current PPI practice in the sexual health field, audits were carried out on PPI
      plans in both service and research sectors. METHODS: 18 local sexual health
      service contacts completed the audit through snowballing. The tool was refined
      and five research projects completed the audit from the Health Protection
      Research Unit in BloodBorne and Sexually Transmitted Infections. Responses were
      collated and a thematic analysis by two independent researchers carried out.
      Common areas for improvement were identified. RESULTS: Audit tool responses
      evidenced wide variability in practice. Issues included conflation of PPI work
      and qualitative research; limited 'patient satisfaction' approaches; lack of PPI
      goals; methodological reliance on 'visible' methods such as focus groups; lack of
      responsiveness around patient needs and poor resourcing of PPI work. Research
      specific issues included 'late' PPI after key decisions had been made and poor
      lay summary validity. DISCUSSION: Two audits evidenced a range of areas for
      improvement of PPI practice in sexual health. Clear definition of 'what PPI is
      for' aligned with evaluation measures would begin to build an evidence base for
      the contribution of patient voice.

PMID- 30228197
TI  - The mTOR Target S6 Kinase Arrests Development in Caenorhabditis elegans When the
      Heat-Shock Transcription Factor Is Impaired.
AB  - The widely conserved heat-shock response, regulated by heat-shock transcription
      factors, is not only essential for cellular stress resistance and adult
      longevity, but also for proper development. However, the genetic mechanisms by
      which heat-shock transcription factors regulate development are not well
      understood. In Caenorhabditis elegans, we conducted an unbiased genetic screen to
      identify mutations that could ameliorate the developmental-arrest phenotype of a
      heat-shock factor mutant. Here, we show that loss of the conserved translational
      activator rsks-1/S6 kinase, a downstream effector of mechanistic Target of
      Rapamycin (mTOR) kinase, can rescue the developmental-arrest phenotype of hsf-1
      partial loss-of-function mutants. Unexpectedly, we show that the rescue is not
      likely caused by reduced translation, nor by activation of any of a variety of
      stress-protective genes and pathways. Our findings identify an as-yet unexplained
      regulatory relationship between the heat-shock transcription factor and the mTOR
      pathway during C. elegans development.

PMID- 30228199
TI  - Crosstalk between alternative polyadenylation and miRNAs in the regulation of
      protein translational efficiency.
AB  - 3' UTRs play important roles in the gene regulation network via their influence
      on mRNA stability, translational efficiency, and subcellular localization. For a
      given gene, 3' UTRs of different lengths generated by alternative polyadenylation
      (APA) may result in functional differences in regulation. The mechanistic details
      of how length changes of 3' UTRs alter gene function remain unclear. By combining
      APA sequencing and polysome profiling, we observed that mRNA isoforms with
      shorter 3' UTRs were bound with more polysomes in six cell lines but not in
      NIH3T3 cells, suggesting that changing 3' UTRs to shorter isoforms may lead to a
      higher gene translational efficiency. By interfering with the expression of
      TNRC6A and analyzing AGO2-PAR-CLIP data, we revealed that the APA effect on
      translational efficiency was mainly regulated by miRNAs, and this regulation was
      cell cycle dependent. The discrepancy between NIH3T3 and other cell lines was due
      to contact inhibition of NIH3T3. Thus, the crosstalk between APA and miRNAs may
      be needed for the regulation of protein translational efficiency.

PMID- 30228201
TI  - Comparison of total-mixed-ration and feed-to-yield strategies on blood profiles
      and dairy cow health.
AB  - Seventy-two Holstein-Friesian dairy cows were offered the same amount of
      concentrates over the first 140 days of lactation, by either a 'total-mixed
      ration' or a 'feed-to-yield' strategy. The effects on blood profiles and cow
      health were examined. Cows on total-mixed-ration were offered a mixed ration
      comprising grass silage and concentrates (50:50 dry matter basis). Cows on feed
      to-yield were offered a basal mixed ration (grass silage plus 6 kg
      concentrates/cow/day) plus additional concentrates via an out-of-parlour feeding
      system, calculated according to each individual cow's milk yield during the
      previous week. Cows on total-mixed-ration had a higher mean haemoglobin, packed
      cell volume and lymphocyte percentage. Concentrate allocation strategy had no
      effect on serum haptoglobin concentrations, interferon-gamma production of
      pokeweed mitogen-stimulated whole blood culture, the incidence of clinical or
      subclinical mastitis, lameness, respiratory or digestive problems and no strong
      relationships were identified between production parameters with serum
      metabolites, inflammatory and immune measures. This study demonstrates small
      physiological differences in metabolic parameters, and no differences in
      inflammatory or immune parameters, when allocating concentrates by total-mixed
      ration or feed-to-yield.

PMID- 30228200
TI  - Transcriptional fates of human-specific segmental duplications in brain.
AB  - Despite the importance of duplicate genes for evolutionary adaptation, accurate
      gene annotation is often incomplete, incorrect, or lacking in regions of
      segmental duplication. We developed an approach combining long-read sequencing
      and hybridization capture to yield full-length transcript information and
      confidently distinguish between nearly identical genes/paralogs. We used
      biotinylated probes to enrich for full-length cDNA from duplicated regions, which
      were then amplified, size-fractionated, and sequenced using single-molecule, long
      read sequencing technology, permitting us to distinguish between highly identical
      genes by virtue of multiple paralogous sequence variants. We examined 19 gene
      families as expressed in developing and adult human brain, selected for their
      high sequence identity (average >99%) and overlap with human-specific segmental
      duplications (SDs). We characterized the transcriptional differences between
      related paralogs to better understand the birth-death process of duplicate genes
      and particularly how the process leads to gene innovation. In 48% of the cases,
      we find that the expressed duplicates have changed substantially from their
      ancestral models due to novel sites of transcription initiation, splicing, and
      polyadenylation, as well as fusion transcripts that connect duplication-derived
      exons with neighboring genes. We detect unannotated open reading frames in genes
      currently annotated as pseudogenes, while relegating other duplicates to
      nonfunctional status. Our method significantly improves gene annotation,
      specifically defining full-length transcripts, isoforms, and open reading frames
      for new genes in highly identical SDs. The approach will be more broadly
      applicable to genes in structurally complex regions of other genomes where the
      duplication process creates novel genes important for adaptive traits.

PMID- 30228202
TI  - Tpr regulates the total number of nuclear pore complexes per cell nucleus.
AB  - The total number of nuclear pore complexes (NPCs) per nucleus varies greatly
      between different cell types and is known to change during cell differentiation
      and cell transformation. However, the underlying mechanisms that control how many
      nuclear transport channels are assembled into a given nuclear envelope remain
      unclear. Here, we report that depletion of the NPC basket protein Tpr, but not
      Nup153, dramatically increases the total NPC number in various cell types. This
      negative regulation of Tpr occurs via a phosphorylation cascade of extracellular
      signal-regulated kinase (ERK), the central kinase of the mitogen-activated
      protein kinase (MAPK) pathway. Tpr serves as a scaffold for ERK to phosphorylate
      the nucleoporin (Nup) Nup153, which is critical for early stages of NPC
      biogenesis. Our results reveal a critical role of the Nup Tpr in coordinating
      signal transduction pathways during cell proliferation and the dynamic
      organization of the nucleus.

PMID- 30228203
TI  - From powerhouse to processing plant: conserved roles of mitochondrial outer
      membrane proteins in tRNA splicing.
AB  - The mitochondrial cytoplasmic surface serves as a processing site for numerous
      RNAs from budding yeast to metazoans. We report that budding yeast mitochondrial
      outer membrane (MOM) proteins that are subunits of the translocase of the outer
      mitochondrial membrane (Tom70 and Tom 22) and sorting and assembly machinery
      (Sam37) are required for efficient pretransfer RNA (pre-tRNA) splicing. Defective
      pre-tRNA splicing in MOM mutants is due not to loss of respiratory metabolism but
      instead inefficient targeting/tethering of tRNA splicing endonuclease (SEN)
      subunits to mitochondria. Schizosaccharomyces pombe SEN subunits also localize to
      mitochondria, and Tom70 is required for this localization and pre-tRNA splicing.
      Thus, the role of MOM protein in targeting/tethering SEN subunits to mitochondria
      has been conserved for >500 million years.

PMID- 30228204
TI  - Regulatory cocktail for dopaminergic neurons in a protovertebrate identified by
      whole-embryo single-cell transcriptomics.
AB  - The CNS of the protovertebrate Ciona intestinalis contains a single cluster of
      dopaminergic (DA) neurons, the coronet cells, which have been likened to the
      hypothalamus of vertebrates. Whole-embryo single-cell RNA sequencing (RNA-seq)
      assays identified Ptf1a as the most strongly expressed cell-specific
      transcription factor (TF) in DA/coronet cells. Knockdown of Ptf1a activity
      results in their loss, while misexpression results in the appearance of
      supernumerary DA/coronet cells. Photoreceptor cells and ependymal cells are the
      most susceptible to transformation, and both cell types express high levels of
      Meis Coexpression of both Ptf1a and Meis caused the wholesale transformation of
      the entire CNS into DA/coronet cells. We therefore suggest that the reiterative
      use of functional manipulations and single-cell RNA-seq assays is an effective
      means for the identification of regulatory cocktails underlying the specification
      of specific cell identities.

PMID- 30228206
TI  - Stromal Cell PD-L1 Inhibits CD8+ T-cell Antitumor Immune Responses and Promotes
      Colon Cancer.
AB  - Stromal cells of mesenchymal origin reside below the epithelial compartment and
      provide structural support in the intestine. These intestinal stromal cells
      interact with both the epithelial cell compartments, as well as infiltrating
      hematopoietic immune cells. The importance of these cells in regulating immune
      homeostasis during inflammation is well recognized. However, little is known
      about their function and phenotype in the inflammatory tumor microenvironment.
      Using a syngeneic, immunogenic model of colorectal cancer, we showed that
      TNFalpha-initiated inflammatory signaling in CT26 colorectal cancer cells
      selectively induced PD-L1 expression in stromal cells. Using CD274 shRNA and
      antibody-mediated approaches, we showed that stromal cell PD-L1 potentiated
      enhanced immunosuppression, characterized by inhibition of activated CD8+
      granzyme B-secreting T cells in vitro, and the inhibition of CD8+ effector cells
      was associated with enhanced tumor progression. Stromal cell immunosuppressive
      and tumor-promoting effects could be reversed with administration of anti-PD-1 in
      vivo We validated our findings of stromal cell CD274 expression in two cohorts of
      clinical samples and also observed PD-L1 induction on human stromal cells in
      response to exposure to the inflammatory secretome from human colon cancer cells,
      irrespective of microsatellite instability. Collectively, our data showed that
      tumor-associated stromal cells support T-cell suppression by PD-L1 induction,
      which is dependent on colon cancer inflammatory signaling. Our findings reveal a
      key role of mesenchymal stromal cells PD-L1 in suppression of CD8+ antitumor
      immune responses and potentiation of colorectal cancer progression. Cancer
      Immunol Res; 6(11); 1426-41. (c)2018 AACR.

PMID- 30228207
TI  - Progranulin aggravates pulmonary immunopathology during influenza virus
      infection.
AB  - Progranulin (PGRN) exerts multiple functions in various inflammatory diseases.
      However, the role of PGRN in the pathogenesis of virus infection is unknown.
      Here, we demonstrated that PGRN production was up-regulated in clinical and
      experimental influenza, which contributed to the deleterious inflammatory
      response after influenza virus infection in mice. PGRN-deficient mice were
      protected from influenza virus-induced lung injury and mortality. Decreased
      mortality was associated with significantly reduced influx of neutrophils and
      monocytes/macrophages, release of cytokines and chemokines, and permeability of
      the alveolar-epithelial barrier without affecting viral clearance. Our findings
      suggest that PGRN exacerbates pulmonary immunopathology during influenza virus
      infection.

PMID- 30228205
TI  - Fusobacterium nucleatum in Colorectal Cancer Relates to Immune Response
      Differentially by Tumor Microsatellite Instability Status.
AB  - The presence of Fusobacterium nucleatum (F. nucleatum) in colorectal carcinoma
      tissue has been associated with microsatellite instability (MSI), lower-level T
      cell infiltrates, and poor clinical outcomes. Considering differences in the
      tumor-immune microenvironment between MSI-high and non-MSI-high carcinomas, we
      hypothesized that the association of F. nucleatum with immune response might
      differ by tumor MSI status. Using samples from 1,041 rectal and colon cancer
      patients within the Nurses' Health Study and Health Professionals Follow-up
      Study, we measured F. nucleatum DNA in tumor tissue by a quantitative polymerase
      chain reaction assay. Multivariable logistic regression models were used to
      examine the association between F. nucleatum status and histopathologic
      lymphocytic reactions or density of CD3+ cells, CD8+ cells, CD45RO (PTPRC)+
      cells, or FOXP3+ cells in strata of tumor MSI status. We adjusted for potential
      confounders, including CpG island methylator phenotype; LINE-1 methylation; and
      KRAS, BRAF, and PIK3CA mutations. The association of F. nucleatum with tumor
      infiltrating lymphocytes (TIL) and intratumoral periglandular reaction differed
      by tumor MSI status (P interaction = 0.002). The presence of F. nucleatum was
      negatively associated with TIL in MSI-high tumors [multivariable odds ratio (OR),
      0.45; 95% confidence interval (CI), 0.22-0.92], but positively associated with
      TIL in non-MSI-high tumors (multivariable OR 1.91; 95% CI, 1.12-3.25). No
      significant differential association was observed for peritumoral lymphocytic
      reaction, Crohn-like lymphoid reaction, or T-cell densities. In conclusion, the
      association of F. nucleatum with immune response to colorectal carcinoma differs
      by tumor MSI status, suggesting that F. nucleatum and MSI status interact to
      affect antitumor immune reactions. Cancer Immunol Res; 6(11); 1327-36. (c)2018
      AACR See related Spotlight on p. 1290.

PMID- 30228208
TI  - A PET Imaging Strategy for Interrogating Target Engagement and Oncogene Status in
      Pancreatic Cancer.
AB  - Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly
      cancers, with a 5-year survival rate of less than 10%. Physicians often rely on
      biopsy or CT to guide treatment decisions, but these techniques fail to reliably
      measure the actions of therapeutic agents in PDAC. KRAS mutations are present in
      >90% of PDAC and are connected to many signaling pathways through its oncogenic
      cascade, including extracellular regulated kinase (ERK) and MYC. A key downstream
      event of MYC is transferrin receptor (TfR), which has been identified as a
      biomarker for cancer therapeutics and imaging.Experimental Design: In this study,
      we aimed to test whether zirconium-89 transferrin ([89Zr]Zr-Tf) could measure
      changes in MYC depending on KRAS status of PDAC, and assess target engagement of
      anti-MYC and anti-ERK-targeted therapies.Results: Mice bearing iKras*p53* tumors
      showed significantly higher (P < 0.05) uptake of [89Zr]Zr-Tf in mice withdrawn
      from inducible oncogenic KRAS. A therapy study with JQ1 showed a statistically
      significant decrease (P < 0.05) of [89Zr]Zr-Tf uptake in drug versus vehicle
      treated mice bearing Capan-2 and Suit-2 xenografts. IHC analysis of resected PDAC
      tumors reflects the data observed via PET imaging and radiotracer
      biodistribution.Conclusions: Our study demonstrates that [89Zr]Zr-Tf is a
      valuable tool to noninvasively assess oncogene status and target engagement of
      small-molecule inhibitors downstream of oncogenic KRAS, allowing a quantitative
      assessment of drug delivery. Clin Cancer Res; 1-11. (c)2018 AACR.

PMID- 30228209
TI  - Functional silencing of HSD17B2 in prostate cancer promotes disease progression.
AB  - PURPOSE: Steroidogenic enzymes are essential for prostate cancer development.
      Enzymes inactivating potent androgens were not investigated thoroughly, which
      leads to limited interfere strategies for prostate cancer therapy. Here we
      characterized the clinical relevance, significance and regulation mechanism of
      enzyme HSD17B2 in prostate cancer development. EXPERIMENTAL DESIGN: HSD17B2
      expression was detected with patient specimens and prostate cancer cell lines.
      Function of HSD17B2 in steroidogenesis, AR signaling and tumor growth was
      investigated with prostate cancer cell lines and xenograft model. DNA methylation
      and mRNA alternative splicing were investigated to unveil the mechanisms of
      HSD17B2 regulation. RESULTS: HSD17B2 expression was reduced as prostate cancer
      progresses. 17betaHSD2 decreased potent androgen production by converting
      testosterone (T) or dihydrotestosterone (DHT) to their upstream precursors.
      HSD17B2 overexpression suppressed androgen-induced cell proliferation and
      xenograft growth. Multiple mechanisms were involved in HSD17B2 functional
      silencing including DNA methylation, androgen stimulation and mRNA alternative
      splicing. DNA methylation and T stimulation decreased HSD17B2 mRNA or protein
      level respectively. Two new catalytic-deficient isoforms, generated by
      alternative splicing, bound to wild type 17betaHSD2 and promoted its degradation.
      Splicing factors SRSF1 and SRSF5 participated in the generation of new isoforms.
      CONCLUSION: Our findings provide evidence of the clinical relevance, significance
      and regulation of HSD17B2 in prostate cancer progression, which might provide new
      strategies for clinical management by targeting the functional silencing
      mechanisms of HSD17B2.

PMID- 30228211
TI  - Clinical utility of reflex testing using focused next-generation sequencing for
      management of patients with advanced lung adenocarcinoma.
AB  - AIMS: The growing number of genomically targeted therapies has made genomic
      testing an important part of the care for patients with non-small cell lung
      cancer. However, limited tissue availability, cost and long turnaround times can
      create barriers to efficient genomic testing and subsequent treatment. Effective
      approaches to reduce these barriers are needed. METHODS: 302 advanced lung
      adenocarcinomas from consecutive patients seen at University Hospitals Cleveland
      Medical Center (UHCMC) were tested inhouse using a hybrid DNA/RNA next-generation
      sequencing (NGS) panel. Sample testing was reflexed from pathology for all stage
      III or IV tumours. Genomic alterations were tiered according to their clinical
      relevance and reported with guideline-recommended therapies. Clinical
      implications of genomic testing results were assessed by manual chart review.
      RESULTS: With a sample cohort consisting of 64% biopsies, 16%
      excisions/resections and 20% fine needle aspirations, the assay was reliable with
      a 95% success rate. The average turnaround time from receipt of unstained
      formalin-fixed paraffin embedded slides to reporting was 4.8+/-2.1 days, half of
      the recommended 10 days and similar to single-gene testing. Alterations with Food
      and Drug Administration-approved or the National Cancer Center Network guideline
      recommended targeted therapies were found in 18% of cases. Within this group, 60%
      of patients went on genomically driven therapies. CONCLUSIONS: We found our
      reflexed inhouse NGS assay to be reliable, cost-effective and efficient.
      Incorporation of reflex testing with our NGS assay led to an expansion of
      successful genomic profiling for all guideline-recommended alterations, and by
      including an expanded number of alterations within our panel we obtained
      clinically useful information outside the guidelines without changing cost or
      efficiency. This approach has enabled UHCMC clinicians to efficiently initiate
      genomically driven therapies for patients with lung adenocarcinoma.

PMID- 30228210
TI  - Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib
      and Continuation Therapy Beyond Progression in EGFR-Mutant NSCLC.
AB  - Purpose: Osimertinib was initially approved for T790M-positive non-small cell
      lung cancer (NSCLC) and, more recently, for first-line treatment of EGFR-mutant
      NSCLC. However, resistance mechanisms to osimertinib have been incompletely
      described.Experimental Design: Using cohorts from The University of Texas MD
      Anderson Lung Cancer Moonshot GEMINI and Moffitt Cancer Center lung cancer
      databases, we collected clinical data for patients treated with osimertinib.
      Molecular profiling analysis was performed at the time of progression in a subset
      of the patients.Results: In the 118 patients treated with osimertinib, 42 had
      molecular profiling at progression. T790M was preserved in 21 (50%) patients and
      lost in 21 (50%). EGFR C797 and L792 (26%) mutations were the most common
      resistance mechanism and were observed exclusively in T790M-preserved cases. MET
      amplification was the second most common alteration (14%). Recurrent alterations
      were observed in 22 genes/pathways, including PIK3CA, FGFR, and RET. Preclinical
      studies confirmed MET, PIK3CA, and epithelial-to-mesenchymal transition as
      potential resistance drivers. Alterations of cell-cycle genes were associated
      with shorter median progression-free survival (PFS, 4.4 vs. 8.8 months, P =
      0.01). In 76 patients with progression, osimertinib was continued in 47 cases
      with a median second PFS (PFS2) of 12.6 months; 21 patients received local
      consolidation radiation with a median PFS of 15.5 months. Continuation of
      osimertinib beyond progression was associated with a longer overall survival
      compared with discontinuation (11.2 vs. 6.1 months, P = 0.02).Conclusions:
      Osimertinib resistance is associated with diverse, predominantly EGFR-independent
      genomic alterations. Continuation of osimertinib after progression, alone or in
      conjunction with radiotherapy, may provide prolonged clinical benefit in selected
      patients. Clin Cancer Res; 24(24); 1-9. (c)2018 AACR.

PMID- 30228212
TI  - Core needle biopsy as an alternative to whole section in IHC4 score assessment
      for breast cancer prognostication.
AB  - AIMS: IHC4 score, based on expression of four routine markers (oestrogen receptor
      (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)
      and proliferation marker, Ki67), is a recently developed, cost-effective
      prognostic tool in breast cancer. Possibly, the score may be useful also in
      advanced diseases where only core needle biopsy (CNB) is available and
      neoadjuvant therapy. However, its studies on CNB are scant. This study examined
      whether IHC4 score assessment on CNB is comparable to that from whole section
      (WS). METHODS: Immunohistochemical (IHC) analysis was performed for ER, PR, HER2
      and Ki67 on 108 paired CNB and WS to evaluate IHC4 score (with follow-up range 1
      230 months and 5 relapse/death). Concordance between the two was examined.
      Factors that affected the concordance were analysed. Additionally, IHC4 score was
      compared with Nottingham Prognostic Index (NPI). RESULTS: There was moderate
      concordance between IHC4 score on CNB and WS (all cases: kappa=0.699, p<0.001;
      ER+ cases: kappa=0.595, p<0.001). Among the IHC4 components, concordance for HER2
      was the poorest (kappa=0.178, p<0.001 in all cases; ER+ cases: kappa=0.082,
      p<0.097). Significant factors affecting concordance between CNB and WS included
      number of cores, total core length and percentage of tumour cells in cores
      (p<=0.030), indicating the importance of sufficient sampling. Interestingly, the
      concordance was also affected by patients' age (p=0.039). There was poor
      agreement between IHC4 score and NPI (kappa<=0.160). CONCLUSION: Our results
      suggested that IHC4 score can be used on adequately sampled CNB. Its poor
      agreement with NPI highlights the independence of the two factors.

PMID- 30228213
TI  - Laboratory assessment of folate (vitamin B9) status.
AB  - Folate (vitamin B9) plays a crucial role in fundamental cellular processes,
      including nucleic acid biosynthesis, methyl group biogenesis and amino acid
      metabolism. The detection and correction of folate deficiency prevents
      megaloblastic anaemia and reduces the risk of neural tube defects. Coexisting
      deficiencies of folate and vitamin B12 are associated with cognitive decline,
      depression and neuropathy. Folate deficiency and excess has also been implicated
      in some cancers. Excessive exposure to folic acid, a synthetic compound used in
      supplements and fortified foods, has also been linked to adverse health effects.
      Of at least three distinct laboratory markers of folate status, it is the total
      abundance of folate in serum/plasma that is used by the majority of laboratories.
      The analysis of folate in red cells is also commonly performed. Since the folate
      content of red cells is fixed during erythropoiesis, this marker is indicative of
      folate status over the preceding ~4 months. Poor stability, variation in
      polyglutamate chain length and unreliable extraction from red cells are factors
      that make the analysis of folate challenging. The clinical use of measuring
      specific folate species has also been explored. 5-Methyltetrahydrofolate, the
      main form of folate found in blood, is essential for the vitamin B12-dependent
      methionine synthase mediated remethylation of homocysteine to methionine. As
      such, homocysteine measurement reflects cellular folate and vitamin B12 use. When
      interpreting homocysteine results, age, sex and pregnancy, specific reference
      ranges should be applied. The evaluation of folate status using combined markers
      of abundance and cellular use has been adopted by some laboratories. In the
      presence of discordance between laboratory results and strong clinical features
      of deficiency, treatment should not be delayed. High folate status should be
      followed up with the assessment of vitamin B12 status, a review of previous
      results and reassessment of folic acid supplementation regime.

PMID- 30228214
TI  - Reagent-saving immunohistochemistry for HER2 using non-contact alternating
      current electric field mixing.
AB  - AIMS: Human epidermal growth factor receptor 2 (HER2)-targeted agents are an
      effective approach to treating patients with HER2-positive breast cancer.
      However, the lack of survival benefit in HER2-negative patients, as well as the
      toxic effects and high cost of the drugs, highlight the need for accurate and
      prompt assessment of HER2 status. Our aim was to evaluate the clinical utility of
      a novel reagent-saving immunohistochemistry method (AC-IHC) that saves HER2
      antibody by taking advantage of the non-contact mixing effect in microdroplets
      subjected to an alternating current electric field. METHODS: Ninety-five
      specimens were used from patients diagnosed with primary breast cancers
      identified immunohistochemically as HER2 0/1+, 2+ or 3+ using ASCO/CAP guideline
      certified standard IHC. The specimens were all tested using the conventional IHC
      method (1:50 antibody dilution) as well as AC-IHC (1:50 dilution) and reagent
      saving AC-IHC (1:100 dilution). RESULTS: The reagent-saving AC-IHC produced
      stable results with less non-specific staining using smaller amounts of labelled
      antibody. Moreover, the staining and accuracy of HER2 status evaluated with the
      reagent-saving AC-IHC method was equal to that achieved with standard IHC.
      CONCLUSIONS: These results suggest reagent-saving AC-IHC could be used as a
      clinical tool for accurate and stable HER2 IHC, even when reagent concentrations
      vary.

PMID- 30228215
TI  - Frequencies and patterns of laboratory test requests from general practice: a
      service evaluation to inform point-of-care testing.
AB  - AIMS: The demand for test requests from general practice to laboratory services
      remains high. Tests performed at the point of care could reduce turnaround time
      and speed up clinical decision making. Replicating laboratory testing in the
      community would require panels of tests to be performed simultaneously, which is
      now approaching technological feasibility. We assessed frequencies and
      combinations of test requests from community settings to inform the potential
      future development of multiplex point-of-care panels. METHODS: We assessed all
      laboratory test requests made from general practice in Oxfordshire, UK, from
      January 2014 to March 2017. We summarised test request frequency overall and in
      combination, using heatmaps and hierarchical cluster analysis. Results are also
      presented by age/sex subgroups. We further assessed patterns of tests requested
      within 7 and 14 days after an initial test request. RESULTS: 11 763 473 test
      requests were made for 413 073 individuals (28% age >65). Of more than 500 test
      types, 62 were requested at least 5000 times, most commonly renal function tests
      (approximately 296 000/year), full blood count (278 000/year) and liver function
      tests (237 000/year). Cluster analysis additionally identified a clear grouping
      of tests commonly used to investigate anaemia. Follow-up test frequency was much
      lower than the frequency of multiple tests ordered at initial presentation.
      CONCLUSIONS: The current high volume of single and combination test requests
      highlights an opportunity for reliable multiplex point-of-care panels to cover a
      core set of frequently requested tests. The impact on test use of introducing
      such panels to general practice requires additional research.

PMID- 30228216
TI  - Changes in neuromuscular structure and functions of human colon during ageing are
      region-dependent.
AB  - OBJECTIVE: To determine if human colonic neuromuscular functions decline with
      increasing age. DESIGN: Looking for non-specific changes in neuromuscular
      function, a standard burst of electrical field stimulation (EFS) was used to
      evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxations in ex
      vivomuscle strips of human ascending and descending colon, aged 35-91 years
      (macroscopically normal tissue; 239 patients undergoing cancer resection). Then,
      to understand mechanisms of change, numbers and phenotype of myenteric neurons
      (30 306 neurons stained with different markers), densities of intramuscular nerve
      fibres (51 patients in total) and pathways involved in functional changes were
      systematically investigated (by immunohistochemistry and use of pharmacological
      tools) in elderly (>=70 years) and adult (35-60 years) groups. RESULTS: With
      increasing age, EFS was more likely to evoke muscle relaxation in ascending colon
      instead of contraction (linear regression: n=109, slope 0.49%+/-0.21%/year, 95%
      CI), generally uninfluenced by comorbidity or use of medications. Similar changes
      were absent in descending colon. In the elderly, overall numbers of myenteric and
      neuronal nitric oxide synthase-immunoreactive neurons and intramuscular nerve
      densities were unchanged in ascending and descending colon, compared with adults.
      In elderly ascending, not descending, colon numbers of cell bodies exhibiting
      choline acetyltransferase immunoreactivity increased compared with adults (5.0+/
      0.6 vs 2.4+/-0.3 neurons/mm myenteric plexus, p=0.04). Cholinergically mediated
      contractions were smaller in elderly ascending colon compared with adults (2.1+/
      0.4 and 4.1+/-1.1 g-tension/g-tissue during EFS; n=25/14; p=0.04); there were no
      changes in nitrergic function or in ability of the muscle to contract/relax.
      Similar changes were absent in descending colon. CONCLUSION: In ascending not
      descending colon, ageing impairs cholinergic function.

PMID- 30228217
TI  - Virtual reality in GI endoscopy: intuitive zoom for improving diagnostics and
      training.

PMID- 30228218
TI  - Antipruritic effect of bezafibrate and serum autotaxin measures in patients with
      primary biliary cholangitis.

PMID- 30228219
TI  - ARID1A, a SWI/SNF subunit, is critical to acinar cell homeostasis and
      regeneration and is a barrier to transformation and epithelial-mesenchymal
      transition in the pancreas.
AB  - OBJECTIVE: Here, we evaluate the contribution of AT-rich interaction domain
      containing protein 1A (ARID1A), the most frequently mutated member of the
      SWItch/sucrose non-fermentable (SWI/SNF) complex, in pancreatic homeostasis and
      pancreatic ductal adenocarcinoma (PDAC) pathogenesis using mouse models. DESIGN:
      Mice with a targeted deletion of Arid1a in the pancreas by itself and in the
      context of two common genetic alterations in PDAC, Kras and p53, were followed
      longitudinally. Pancreases were examined and analysed for proliferation, response
      to injury and tumourigenesis. Cancer cell lines derived from these models were
      analysed for clonogenic, migratory, invasive and transcriptomic changes. RESULTS:
      Arid1a deletion in the pancreas results in progressive acinar-to-ductal
      metaplasia (ADM), loss of acinar mass, diminished acinar regeneration in response
      to injury and ductal cell expansion. Mutant Kras cooperates with homozygous
      deletion of Arid1a, leading to intraductal papillary mucinous neoplasm (IPMN).
      Arid1a loss in the context of mutant Kras and p53 leads to shorter tumour
      latency, with the resulting tumours being poorly differentiated. Cancer cell
      lines derived from Arid1a-mutant tumours are more mesenchymal, migratory,
      invasive and capable of anchorage-independent growth; gene expression analysis
      showed activation of epithelial-mesenchymal transition (EMT) and stem cell
      identity pathways that are partially dependent on Arid1a loss for dysregulation.
      CONCLUSIONS: ARID1A plays a key role in pancreatic acinar homeostasis and
      response to injury. Furthermore, ARID1A restrains oncogenic KRAS-driven formation
      of premalignant proliferative IPMN. Arid1a-deficient PDACs are poorly
      differentiated and have mesenchymal features conferring migratory/invasive and
      stem-like properties.

PMID- 30228220
TI  - Prevalence and burden of hepatitis D virus infection in the global population: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Hepatitis D virus (HDV) is a defective virus that completes its life
      cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has
      been considered as one of the most severe forms of the chronic viral hepatitis.
      However, there is a scarcity of data on the global burden of HDV infection.
      DESIGN: We searched PubMed, Embase, Cochrane Library and China Knowledge Resource
      Integrated databases from 1 January 1977 to 31 December 2016. We included studies
      with a minimum sample size of 50 patients. Our study analysed data from a total
      of 40 million individuals to estimate the prevalence of HDV by using Der-Simonian
      Laird random-effects model. The data were further categorised according to risk
      factors. RESULTS: From a total of 2717 initially identified studies, only 182
      articles from 61 countries and regions met the final inclusion criteria. The
      overall prevalence of HDV was 0.98% (95% CI 0.61 to 1.42). In HBsAg-positive
      population, HDV pooled prevalence was 14.57% (95% CI 12.93 to 16.27):
      Seroprevalence was 10.58% (95% CI 9.14 to 12.11) in mixed population without risk
      factors of intravenous drug use (IVDU) and high-risk sexual behaviour (HRSB). It
      was 37.57% (95% CI 29.30 to 46.20) in the IVDU population and 17.01% (95% CI
      10.69 to 24.34) in HRSB population. CONCLUSION: We found that approximately
      10.58% HBsAg carriers (without IVDU and HRSB) were coinfected with HDV, which is
      twofold of what has been estimated before. We also noted a substantially higher
      HDV prevalence in the IVDU and HRSB population. Our study highlights the need for
      increased focus on the routine HDV screening and rigorous implementation of HBV
      vaccine programme.

PMID- 30228221
TI  - Impact of federal transfers upon US infant mortality rates: a secondary analysis
      using a fixed effects regression approach.
AB  - OBJECTIVES: In order to improve health outcomes, the federal government allocates
      hundreds of billions of annual dollars to individual states in order to further
      the well-being of its citizens. This study examines the impact of such federal
      intergovernmental transfers on reducing state-level infant mortality rates.
      SETTING: Annual data are collected from all 50 US states between 2004 and 2013.
      PARTICIPANTS: Entire US population under the age of 1 year between 2004 and 2013.
      PRIMARY AND SECONDARY OUTCOME MEASURES: State-level infant mortality rate,
      neonatal mortality rate and postneonatal mortality rate. RESULTS: Using a fixed
      effects regression model to control for unmeasurable differences between states,
      the impact of federal transfers on state-level infant mortality rates is
      estimated. After controlling for differences across states, increases in per
      capita federal transfers are significantly associated with lower infant, neonatal
      and postneonatal mortality rates. Holding all other variables constant, a $200
      increase in the amount of federal transfers per capita would save one child's
      life for every 10 000 live births. CONCLUSIONS: Considerable debate exists
      regarding the role of federal transfers in improving the well-being of children
      and families. These findings indicate that increases in federal transfers are
      strongly associated with reductions in infant mortality rates. Such benefits
      should be carefully considered when state officials are deciding whether to
      accept or reject federal funds.

PMID- 30228222
TI  - Acting by persuasion- values and rhetoric in medical certificates of work
      incapacity: A qualitative document analysis.
AB  - When the patient applies for disability benefit in Norway, the general
      practitioner (GP) is required by the National Insurance Administration (NAV) to
      confirm that the patient is unfit for work due to disease. Considering the
      important social role of medical certificates, they have been given surprisingly
      little attention by the medical critique. They may make essential differences to
      peoples' lives, legitimise large social costs and, in addition, the GPs report
      that issuing certificates can be problematic. This article explores values,
      attitudes and persuasive language in a selection of medical certificates written
      by GPs. We direct attention to such texts as significant social actors using a
      mixed rhetoric including certain values and attitudes. When arguing for granting
      the patient disability benefit, some GPs emphasised the 'worthiness' of the
      patient by pointing to positive attitudes approved by the national insurance: a
      will to work and participate, to cooperate and be motivated. Others pointed out
      the patient's positive character in terms of universally accepted values, called
      for the reader's (the NAV official) sympathy , understanding and helpfulness or
      appealed to his/her willingness to be realistic and pragmatic and grant
      disability benefit (DB). The dialogic style varied: some certifiers-although they
      argued for disability benefit-showed openness to possible opposing or alternative
      voices by displaying their own uncertainty. Others addressed the reader to share
      responsibility, demanding or urging for DB. This shifting rhetoric, we believe,
      mirrors that the GPs see themselves as the patient's advocate, and that they may
      find themselves conflicted. We propose further studies within qualitative
      research to investigate the effect of this rhetoric on the reader, the decision
      makers. In addition, to improve the quality and accuracy of these important
      documents, we suggest that medical schools introduce students to the making of
      text as a specific skill of medical practice.

PMID- 30228223
TI  - Graphic illustration of impairment: science fiction, Transmetropolitan and the
      social model of disability.
AB  - The following paper examines the cyberpunk transhumanist graphic novel
      Transmetropolitan through the theoretical lens of disability studies to
      demonstrate how science fiction, and in particular this series, illustrate and
      can influence how we think about disability, impairment and difference. While
      Transmetropolitan is most often read as a scathing political and social satire
      about abuse of power and the danger of political apathy, the comic series also
      provides readers with representations of impairment and the source of disability
      as understood by the Social Model of Disability (SMD). Focusing on the setting
      and fictional world in which Transmetropolitan takes place, as well as key events
      and illustration styling, this paper demonstrates that the narrative in this work
      encompasses many of the same theoretical underpinnings and criticisms of
      society's ignorance of the cause of disability as the SMD does. This paper aims,
      by demonstrating how Transmetropolitan can be read as an allegory for the
      disabling potential of society as experienced by individuals with impairments, to
      prompt readers into thinking more creatively about how narratives, seemingly
      unconcerned with disability, are informed and can be understood via disability
      theory.

PMID- 30228224
TI  - Single-molecule diffusion-based estimation of ligand effects on G protein-coupled
      receptors.
AB  - G protein-coupled receptors (GPCRs) are major drug targets. Developing a method
      to measure the activities of GPCRs is essential for pharmacology and drug
      screening. However, it is difficult to measure the effects of a drug by
      monitoring the receptor on the cell surface; thus, changes in the concentrations
      of downstream signaling molecules, which depend on the signaling pathway
      selectivity of the receptor, are often used as an index of receptor activity. We
      show that single-molecule imaging analysis provides an alternative method for
      assessing the effects of ligands on GPCRs. Using total internal reflection
      fluorescence microscopy (TIRFM), we monitored the dynamics of the diffusion of
      metabotropic glutamate receptor 3 (mGluR3), a class C GPCR, under various ligand
      conditions. Our single-molecule tracking analysis demonstrated that increases and
      decreases in the average diffusion coefficient of mGluR3 quantitatively reflected
      the ligand-dependent inactivation and activation of receptors, respectively.
      Through experiments with inhibitors and dual-color single-molecule imaging
      analysis, we found that the diffusion of receptor molecules was altered by common
      physiological events associated with GPCRs, including G protein binding, and
      receptor accumulation in clathrin-coated pits. We also confirmed that agonist
      also decreased the average diffusion coefficient for class A and B GPCRs,
      demonstrating that this parameter is a good index for estimating ligand effects
      on many GPCRs regardless of their phylogenetic groups, the chemical properties of
      the ligands, or G protein-coupling selectivity.

PMID- 30228225
TI  - Ca2+ concentration-dependent premature death of igfbp5a-/- fish reveals a
      critical role of IGF signaling in adaptive epithelial growth.
AB  - The phenotype gap is a challenge for genetically dissecting redundant endocrine
      signaling pathways, such as the six isoforms in the insulin-like growth factor
      binding protein (IGFBP) family. Although overexpressed IGFBPs can inhibit or
      potentiate IGF actions or have IGF-independent actions, mutant mice lacking IGFBP
      encoding genes do not exhibit major phenotypes. We found that although zebrafish
      deficient in igfbp5a did not show overt phenotypes when raised in Ca2+-rich
      solutions, they died prematurely in low Ca2+ conditions. A group of epithelial
      cells expressing igfbp5a take up Ca2+ and proliferate under low Ca2+ conditions
      because of activation of IGF signaling. Deletion of igfbp5a blunted low Ca2+
      stress-induced IGF signaling and impaired adaptive proliferation. Reintroducing
      zebrafish Igfbp5a, but not its ligand binding-deficient mutant, restored adaptive
      proliferation. Similarly, adaptive proliferation was restored in zebrafish
      lacking igfbp5a by expression of human IGFBP5, but not two cancer-associated
      IGFBP5 mutants. Knockdown of IGFBP5 in human colon carcinoma cells resulted in
      reduced IGF-stimulated cell proliferation. These results reveal a conserved
      mechanism by which a locally expressed Igfbp regulates organismal Ca2+
      homeostasis and survival by activating IGF signaling in epithelial cells and
      promoting their proliferation in Ca2+-deficient states. These findings underscore
      the importance of physiological context when analyzing loss-of-function
      phenotypes of endocrine factors.

PMID- 30228226
TI  - The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF
      receptors by recruiting Src kinases.
AB  - Sustained activation of extracellular signal-regulated kinase (ERK) drives
      pathologies caused by mutations in fibroblast growth factor receptors (FGFRs). We
      previously identified the inositol phosphatase SHIP2 (also known as INPPL1) as an
      FGFR-interacting protein and a target of the tyrosine kinase activities of FGFR1,
      FGFR3, and FGFR4. We report that loss of SHIP2 converted FGF-mediated sustained
      ERK activation into a transient signal and rescued cell phenotypes triggered by
      pathologic FGFR-ERK signaling. Mutant forms of SHIP2 lacking phosphoinositide
      phosphatase activity still associated with FGFRs and did not prevent FGF-induced
      sustained ERK activation, demonstrating that the adaptor rather than the
      catalytic activity of SHIP2 was required. SHIP2 recruited Src family kinases to
      the FGFRs, which promoted FGFR-mediated phosphorylation and assembly of protein
      complexes that relayed signaling to ERK. SHIP2 interacted with FGFRs, was
      phosphorylated by active FGFRs, and promoted FGFR-ERK signaling at the level of
      phosphorylation of the adaptor FRS2 and recruitment of the tyrosine phosphatase
      PTPN11. Thus, SHIP2 is an essential component of canonical FGF-FGFR signal
      transduction and a potential therapeutic target in FGFR-related disorders.

PMID- 30228228
TI  - Anterior Temporal Lobectomy Impairs Neural Classification of Body Emotions in
      Right Superior Temporal Sulcus and Reduces Emotional Enhancement in Distributed
      Brain Areas without Affecting Behavioral Classification.
AB  - Humans with amygdalar lesions show proportional reductions of the emotional
      response to facial expressions in the fusiform face area as well as deficits in
      emotion recognition from facial expressions. While processing of bodily
      expressions shares many similarities with facial expressions, there is no
      substantial evidence that lesions of the amygdala result in similar behavioral
      and neural sequelae. We combined behavioral assessment with functional
      neuroimaging in a group of male and female humans with unilateral anterior
      temporal lobe (ATL) resections, including the amygdala (right: n = 10; left: n =
      10) and 12 matched controls. The objective was to assess whether the amygdala is
      crucial for the recognition of body expressions and for modulatory effects on
      distant areas during perception of body expressions. The behavioral results
      revealed normal performance in both patient groups on emotion categorization of
      body expressions. The neuroimaging results showed that ATL patients displayed no
      enhanced activations in right fusiform body area and left extrastriate body area
      and that left ATL patients additionally displayed no enhanced activations in
      right posterior superior temporal sulcus and right extrastriate body area,
      respectively. Multivoxel pattern analysis revealed altered categorization
      capacity between emotional and neutral stimuli in right posterior superior
      temporal sulcus in right ATL patients. In addition, we also found emotional
      enhancement in frontal, parietal, occipital, and cingulate regions in controls.
      Together, our data show that the amygdala and ATLs are not necessary for
      recognition of dynamic body expressions, but suggest that amygdala lesions affect
      body emotion processing in distant brain areas.SIGNIFICANCE STATEMENT For humans,
      information from emotional expressions of others is crucial to support social
      interactions. The majority of emotion studies has focused on facial expressions;
      however, in daily life, we also use information from body postures and body
      movement. Visual processing of body expressions relies on a brain network,
      including body-specific visual areas and visuomotor areas. Even though the
      importance of the amygdala and its modulatory effects on distant brain regions
      have been documented, it remains unclear whether the amygdala plays a crucial
      role in emotional body processing. By combining behavioral and neuroimaging data
      in patients with amygdalar lesions, we provide further evidence for its
      modulatory effect on distant areas during the perception of body expressions.

PMID- 30228227
TI  - CREST in the Nucleus Accumbens Core Regulates Cocaine Conditioned Place
      Preference, Cocaine-Seeking Behavior, and Synaptic Plasticity.
AB  - Epigenetic mechanisms result in persistent changes at the cellular level that can
      lead to long-lasting behavioral adaptations. Nucleosome remodeling is a major
      epigenetic mechanism that has not been well explored with regards to drug-seeking
      behaviors. Nucleosome remodeling is performed by multi-subunit complexes that
      interact with DNA or chromatin structure and possess an ATP-dependent enzyme to
      disrupt nucleosome-DNA contacts and ultimately regulate gene expression. Calcium
      responsive transactivator (CREST) is a transcriptional activator that interacts
      with enzymes involved in both histone acetylation and nucleosome remodeling.
      Here, we examined the effects of knocking down CREST in the nucleus accumbens
      (NAc) core on drug-seeking behavior and synaptic plasticity in male mice as well
      as drug-seeking in male rats. Knocking down CREST in the NAc core results in
      impaired cocaine-induced conditioned place preference (CPP) as well as theta
      induced long-term potentiation in the NAc core. Further, similar to the CPP
      findings, using a self-administration procedure, we found that CREST knockdown in
      the NAc core of male rats had no effect on instrumental responding for cocaine
      itself on a first-order schedule, but did significantly attenuate responding on a
      second-order chain schedule, in which responding has a weaker association with
      cocaine. Together, these results suggest that CREST in the NAc core is required
      for cocaine-induced CPP, synaptic plasticity, as well as cocaine-seeking
      behavior.SIGNIFICANCE STATEMENT This study demonstrates a key role for the role
      of Calcium responsive transactivator (CREST), a transcriptional activator, in the
      nucleus accumbens (NAc) core with regard to cocaine-induced conditioned place
      preference (CPP), self-administration (SA), and synaptic plasticity. CREST is a
      unique transcriptional regulator that can recruit enzymes from two different
      major epigenetic mechanisms: histone acetylation and nucleosome remodeling. In
      this study we also found that the level of potentiation in the NAc core
      correlated with whether or not animals formed a CPP. Together the results
      indicate that CREST is a key downstream regulator of cocaine action in the NAc.

PMID- 30228229
TI  - A Subpopulation of Foxj1-Expressing, Nonmyelinating Schwann Cells of the
      Peripheral Nervous System Contribute to Schwann Cell Remyelination in the Central
      Nervous System.
AB  - New myelin sheaths can be restored to demyelinated axons in a spontaneous
      regenerative process called remyelination. In general, new myelin sheaths are
      made by oligodendrocytes newly generated from a widespread population of adult
      CNS progenitors called oligodendrocyte progenitor cells (OPCs). New myelin in CNS
      remyelination in both experimental models and clinical diseases can also be
      generated by Schwann cells (SCs), the myelin-forming cells of the PNS. Fate
      mapping studies have shown that SCs contributing to remyelination in the CNS are
      often derived from OPCs and appear not to be derived from myelinating SCs from
      the PNS. In this study, we address whether CNS remyelinating SCs can also be
      generated from PNS-derived cells other than myelinating SCs. Using a genetic fate
      mapping approach, we have found that a subpopulation of nonmyelinating SCs
      identified by the expression of the transcription factor Foxj1 also contribute to
      CNS SC remyelination, as well as to remyelination in the PNS. We also find that
      the ependymal cells lining the central canal of the spinal cord, which also
      express Foxj1, do not generate cells that contribute to CNS remyelination. These
      findings therefore identify a previously unrecognized population of PNS glia that
      can participate in the regeneration of new myelin sheaths following CNS
      demyelination.SIGNIFICANCE STATEMENT Remyelination failure in chronic
      demyelinating diseases such as multiple sclerosis drives the current quest for
      developing means by which remyelination in CNS can be enhanced therapeutically.
      Critical to this endeavor is the need to understand the mechanisms of
      remyelination, including the nature and identity of the cells capable of
      generating new myelin sheath-forming cells. Here, we report a previously
      unrecognized subpopulation of nonmyelinating Schwann cells (SCs) in the PNS,
      identified by the expression of the transcription factor Foxj1, which can give
      rise to SCs that are capable of remyelinating both PNS and CNS axons. These cells
      therefore represent a new cellular target for myelin regenerative strategies for
      the treatment of CNS disorders characterized by persistent demyelination.

PMID- 30228230
TI  - Neogenin in Amygdala for Neuronal Activity and Information Processing.
AB  - Fear learning and memory are vital for livings to survive, dysfunctions in which
      have been implicated in various neuropsychiatric disorders. Appropriate neuronal
      activation in amygdala is critical for fear memory. However, the underlying
      regulatory mechanisms are not well understood. Here we report that Neogenin, a
      DCC (deleted in colorectal cancer) family receptor, which plays important roles
      in axon navigation and adult neurogenesis, is enriched in excitatory neurons in
      BLA (Basolateral amygdala). Fear memory is impaired in male Neogenin mutant mice.
      The number of cFos+ neurons in response to tone-cued fear training was reduced in
      mutant mice, indicating aberrant neuronal activation in the absence of Neogenin.
      Electrophysiological studies show that Neogenin mutation reduced the cortical
      afferent input to BLA pyramidal neurons and compromised both induction and
      maintenance of Long-Term Potentiation evoked by stimulating cortical afferent,
      suggesting a role of Neogenin in synaptic plasticity. Concomitantly, there was a
      reduction in spine density and in frequency of miniature excitatory postsynaptic
      currents (mEPSCs), but not miniature inhibitory postsynaptic currents, suggesting
      a role of Neogenin in forming excitatory synapses. Finally, ablating Neogenin in
      the BLA in adult male mice impaired fear memory likely by reducing mEPSC
      frequency in BLA excitatory neurons. These results reveal an unrecognized
      function of Neogenin in amygdala for information processing by promoting and
      maintaining neurotransmission and synaptic plasticity and provide insight into
      molecular mechanisms of neuronal activation in amygdala.SIGNIFICANCE STATEMENT
      Appropriate neuronal activation in amygdala is critical for information
      processing. However, the underlying regulatory mechanisms are not well
      understood. Neogenin is known to regulate axon navigation and adult neurogenesis.
      Here we show that it is critical for neurotransmission and synaptic plasticity in
      the amygdala and thus fear memory by using a combination of genetic,
      electrophysiological, behavioral techniques. Our studies identify a novel
      function of Neogenin and provide insight into molecular mechanisms of neuronal
      activation in amygdala for fear processing.

PMID- 30228232
TI  - IMiDs prime myeloma cells for daratumumab-mediated cytotoxicity through loss of
      Ikaros and Aiolos.
AB  - Recent studies have demonstrated that the immunomodulatory drugs (IMiDs) lead to
      the degradation of the transcription factors Ikaros and Aiolos. However, why
      their loss subsequently leads to multiple myeloma (MM) cell death remains
      unclear. Using CRISPR-Cas9 genome editing, we have deleted IKZF1/Ikaros and
      IKZF3/Aiolos in human MM cell lines to gain further insight into their downstream
      gene regulatory networks. Inactivation of either factor alone recapitulates the
      cell intrinsic action of the IMiDs, resulting in cell cycle arrest and induction
      of apoptosis. Furthermore, evaluation of the transcriptional changes resulting
      from their loss demonstrates striking overlap with lenalidomide treatment. This
      was not dependent on reduction of the IRF4-MYC "axis," as neither protein was
      consistently downregulated, despite cell death occurring, and overexpression of
      either factor failed to rescue for Ikaros loss. Importantly, Ikaros and Aiolos
      repress the expression of interferon-stimulated genes (ISGs), including CD38, and
      their loss led to the activation of an interferon-like response, contributing to
      MM cell death. Ikaros/Aiolos repressed CD38 expression through interaction with
      the nucleosome remodeling and deacetylase complex in MM. IMiD-induced loss of
      Ikaros or treatment with interferon resulted in an upregulation of CD38 surface
      expression on MM cells, priming for daratumumab-induced NK cell-mediated antibody
      dependent cellular cytotoxicity. These results give further insight into the
      mechanism of action of the IMiDs and provide mechanistic rationale for
      combination with anti-CD38 monoclonal antibodies.

PMID- 30228231
TI  - On the Role of Cortex-Basal Ganglia Interactions for Category Learning: A
      Neurocomputational Approach.
AB  - In addition to the prefrontal cortex (PFC), the basal ganglia (BG) have been
      increasingly often reported to play a fundamental role in category learning, but
      the circuit mechanisms mediating their interaction remain to be explored. We
      developed a novel neurocomputational model of category learning that particularly
      addresses the BG-PFC interplay. We propose that the BG bias PFC activity by
      removing the inhibition of cortico-thalamo-cortical loop and thereby provide a
      teaching signal to guide the acquisition of category representations in the
      corticocortical associations to the PFC. Our model replicates key behavioral and
      physiological data of macaque monkey learning a prototype distortion task from
      Antzoulatos and Miller (2011) Our simulations allowed us to gain a deeper insight
      into the observed drop of category selectivity in striatal neurons seen in the
      experimental data and in the model. The simulation results and a new analysis of
      the experimental data based on the model's predictions show that the drop in
      category selectivity of the striatum emerges as the variability of responses in
      the striatum rises when confronting the BG with an increasingly larger number of
      stimuli to be classified. The neurocomputational model therefore provides new
      testable insights of systems-level brain circuits involved in category learning
      that may also be generalized to better understand other cortico-BG-cortical
      loops.SIGNIFICANCE STATEMENT Inspired by the idea that basal ganglia (BG) teach
      the prefrontal cortex (PFC) to acquire category representations, we developed a
      novel neurocomputational model and tested it on a task that was recently applied
      in monkey experiments. As an advantage over previous models of category learning,
      our model allows to compare simulation data with single-cell recordings in PFC
      and BG. We not only derived model predictions, but already verified a prediction
      to explain the observed drop in striatal category selectivity. When testing our
      model with a simple, real-world face categorization task, we observed that the
      fast striatal learning with a performance of 85% correct responses can teach the
      slower PFC learning to push the model performance up to almost 100%.

PMID- 30228233
TI  - Antithrombotic therapy in abdominal aortic aneurysm: beneficial or detrimental?
AB  - Abdominal aortic aneurysm (AAA) is a degenerative vascular pathology resulting in
      significant morbidity and mortality in older adults due to rupture and sudden
      death. Despite 150,000 new cases and nearly 15,000 deaths annually, the only
      approved treatment for AAA is surgical or endovascular intervention when the risk
      for aortic rupture is increased. The goal of the scientific community is to
      develop novel pharmaceutical treatment strategies to reduce the need for surgical
      intervention. As most clinically-relevant AAAs contain a complex structure of
      fibrin, inflammatory cells, platelets, and red blood cells in the aneurysmal sac
      known as an intraluminal thrombus (ILT), antithrombotic therapies have emerged as
      potential pharmaceutical agents for the treatment of AAA progression. However,
      the efficacy of these treatments has not been shown, and the effects of shrinking
      the ILT may be as detrimental as they are beneficial. This review discusses the
      prospect of anticoagulant and antiplatelet (termed collectively as
      antithrombotic) therapies in AAA. Herein, we discuss the role of the coagulation
      cascade and platelet activation in human and animal models of AAA, the
      composition of ILT in AAA, a possible role of the ILT in aneurysm stabilization,
      and the implications of antithrombotic drugs in AAA treatment.

PMID- 30228234
TI  - Bcor insufficiency promotes initiation and progression of myelodysplastic
      syndrome.
AB  - BCOR, encoding BCL-6 corepressor (BCOR), is X-linked and targeted by somatic
      mutations in various hematological malignancies including myelodysplastic
      syndrome (MDS). We previously reported that mice lacking Bcor exon 4 (Bcor
      DeltaE4/y ) in the hematopoietic compartment developed NOTCH-dependent acute T
      cell lymphoblastic leukemia (T-ALL). Here, we analyzed mice lacking Bcor exons 9
      and 10 (Bcor DeltaE9-10/y ), which express a carboxyl-terminal truncated BCOR
      that fails to interact with core effector components of polycomb repressive
      complex 1.1. Bcor DeltaE9-10/y mice developed lethal T-ALL in a similar manner to
      Bcor DeltaE4/y mice, whereas Bcor DeltaE9-10/y hematopoietic cells showed a
      growth advantage in the myeloid compartment that was further enhanced by the
      concurrent deletion of Tet2 Tet2 Delta/Delta Bcor DeltaE9-10/y mice developed
      lethal MDS with progressive anemia and leukocytopenia, inefficient hematopoiesis,
      and the morphological dysplasia of blood cells. Tet2 Delta/Delta Bcor DeltaE9
      10/y MDS cells reproduced MDS or evolved into lethal MDS/myeloproliferative
      neoplasms in secondary recipients. Transcriptional profiling revealed the
      derepression of myeloid regulator genes of the Cebp family and Hoxa cluster genes
      in Bcor DeltaE9-10/y progenitor cells and the activation of p53 target genes
      specifically in MDS erythroblasts where massive apoptosis occurred. Our results
      reveal a tumor suppressor function of BCOR in myeloid malignancies and highlight
      the impact of Bcor insufficiency on the initiation and progression of MDS.

PMID- 30228235
TI  - Parallel Evolution of Genome Streamlining and Cellular Bioenergetics across the
      Marine Radiation of a Bacterial Phylum.
AB  - Diverse bacterial and archaeal lineages drive biogeochemical cycles in the global
      ocean, but the evolutionary processes that have shaped their genomic properties
      and physiological capabilities remain obscure. Here we track the genome evolution
      of the globally abundant marine bacterial phylum Marinimicrobia across its
      diversification into modern marine environments and demonstrate that extant
      lineages are partitioned between epipelagic and mesopelagic habitats. Moreover,
      we show that these habitat preferences are associated with fundamental
      differences in genomic organization, cellular bioenergetics, and metabolic
      modalities. Multiple lineages present in epipelagic niches independently acquired
      genes necessary for phototrophy and environmental stress mitigation, and their
      genomes convergently evolved key features associated with genome streamlining. In
      contrast, lineages residing in mesopelagic waters independently acquired nitrate
      respiratory machinery and a variety of cytochromes, consistent with the use of
      alternative terminal electron acceptors in oxygen minimum zones (OMZs). Further,
      while epipelagic clades have retained an ancestral Na+-pumping respiratory
      complex, mesopelagic lineages have largely replaced this complex with canonical
      H+-pumping respiratory complex I, potentially due to the increased efficiency of
      the latter together with the presence of the more energy-limiting environments
      deep in the ocean's interior. These parallel evolutionary trends indicate that
      key features of genomic streamlining and cellular bioenergetics have occurred
      repeatedly and congruently in disparate clades and underscore the importance of
      environmental conditions and nutrient dynamics in driving the evolution of
      diverse bacterioplankton lineages in similar ways throughout the global
      ocean.IMPORTANCE Understanding long-term patterns of microbial evolution is
      critical to advancing our knowledge of past and present role microbial life in
      driving global biogeochemical cycles. Historically, it has been challenging to
      study the evolution of environmental microbes due to difficulties in obtaining
      genome sequences from lineages that could not be cultivated, but recent advances
      in metagenomics and single-cell genomics have begun to obviate many of these
      hurdles. Here we present an evolutionary genomic analysis of the Marinimicrobia,
      a diverse bacterial group that is abundant in the global ocean. We demonstrate
      that distantly related Marinimicrobia species that reside in similar habitats
      have converged to assume similar genome architectures and cellular bioenergetics,
      suggesting that common factors shape the evolution of a broad array of marine
      lineages. These findings broaden our understanding of the evolutionary forces
      that have given rise to microbial life in the contemporary ocean.

PMID- 30228236
TI  - The Genome of the Human Pathogen Candida albicans Is Shaped by Mutation and
      Cryptic Sexual Recombination.
AB  - The opportunistic fungal pathogen Candida albicans lacks a conventional sexual
      program and is thought to evolve, at least primarily, through the clonal
      acquisition of genetic changes. Here, we performed an analysis of heterozygous
      diploid genomes from 21 clinical isolates to determine the natural evolutionary
      processes acting on the C. albicans genome. Mutation and recombination shaped the
      genomic landscape among the C. albicans isolates. Strain-specific single
      nucleotide polymorphisms (SNPs) and insertions/deletions (indels) clustered
      across the genome. Additionally, loss-of-heterozygosity (LOH) events contributed
      substantially to genotypic variation, with most long-tract LOH events extending
      to the ends of the chromosomes suggestive of repair via break-induced
      replication. Consistent with a model of inheritance by descent, most
      polymorphisms were shared between closely related strains. However, some isolates
      contained highly mosaic genomes consistent with strains having experienced
      interclade recombination during their evolutionary history. A detailed
      examination of mitochondrial genomes also revealed clear examples of interclade
      recombination among sequenced strains. These analyses therefore establish that
      both (para)sexual recombination and mitotic mutational processes drive evolution
      of this important pathogen. To further facilitate the study of C. albicans
      genomes, we also introduce an online platform, SNPMap, to examine SNP patterns in
      sequenced isolates.IMPORTANCE Mutations introduce variation into the genome upon
      which selection can act. Defining the nature of these changes is critical for
      determining species evolution, as well as for understanding the genetic changes
      driving important cellular processes. The heterozygous diploid fungus Candida
      albicans is both a frequent commensal organism and a prevalent opportunistic
      pathogen. A prevailing theory is that C. albicans evolves primarily through the
      gradual buildup of mitotic mutations, and a pressing issue is whether sexual or
      parasexual processes also operate within natural populations. Here, we establish
      that the C. albicans genome evolves by a combination of localized mutation and
      both short-tract and long-tract loss-of-heterozygosity (LOH) events within the
      sequenced isolates. Mutations are more prevalent within noncoding and
      heterozygous regions and LOH increases towards chromosome ends. Furthermore, we
      provide evidence for genetic exchange between isolates, establishing that sexual
      or parasexual processes have contributed to the diversity of both nuclear and
      mitochondrial genomes.

PMID- 30228237
TI  - Inhibition of Rho Activity Increases Expression of SaeRS-Dependent Virulence
      Factor Genes in Staphylococcus aureus, Showing a Link between Transcription
      Termination, Antibiotic Action, and Virulence.
AB  - Staphylococcus aureus causes various diseases ranging from skin and soft tissue
      infections to life-threatening infections. Adaptation to the different host
      niches is controlled by a complex network of transcriptional regulators. Global
      profiling of condition-dependent transcription revealed adaptation of S. aureus
      HG001 at the levels of transcription initiation and termination. In particular,
      deletion of the gene encoding the Rho transcription termination factor triggered
      a remarkable overall increase in antisense transcription and gene expression
      changes attributable to indirect regulatory effects. The goal of the present
      study was a detailed comparative analysis of S. aureus HG001 and its isogenic rho
      deletion mutant. Proteome analysis revealed significant differences in cellular
      and extracellular protein profiles, most notably increased amounts of the
      proteins belonging to the SaeR regulon in the Rho-deficient strain. The SaeRS two
      component system acts as a major regulator of virulence gene expression in
      staphylococci. Higher levels of SaeRS-dependent virulence factors such as
      adhesins, toxins, and immune evasion proteins in the rho mutant resulted in
      higher virulence in a murine bacteremia model, which was alleviated in a rho
      complemented strain. Inhibition of Rho activity by bicyclomycin, a specific
      inhibitor of Rho activity, also induced the expression of SaeRS-dependent genes,
      at both the mRNA and protein levels, to the same extent as observed in the rho
      mutant. Taken together, these findings indicate that activation of the Sae system
      in the absence of Rho is directly linked to Rho's transcription termination
      activity and establish a new link between antibiotic action and virulence gene
      expression in S. aureusIMPORTANCE The major human pathogen Staphylococcus aureus
      is a widespread commensal bacterium but also the most common cause of nosocomial
      infections. It adapts to the different host niches through a complex gene
      regulatory network. We show here that the Rho transcription termination factor,
      which represses pervasive antisense transcription in various bacteria, including
      S. aureus, plays a role in controlling SaeRS-dependent virulence gene expression.
      A Rho-deficient strain produces larger amounts of secreted virulence factors in
      vitro and shows increased virulence in mice. We also show that treatment of S.
      aureus with the antibiotic bicyclomycin, which inhibits Rho activity and is
      effective against Gram-negative bacteria, induces the same changes in the
      proteome as observed in the Rho-deficient strain. Our results reveal for the
      first time a link between transcription termination and virulence regulation in
      S. aureus, which implies a novel mechanism by which an antibiotic can modulate
      the expression of virulence factors.

PMID- 30228238
TI  - The Microbiome and Tuberculosis: Early Evidence for Cross Talk.
AB  - Tuberculosis (TB) is an ancient infectious disease of humans that has been
      extensively studied both clinically and experimentally. Although susceptibility
      to Mycobacterium tuberculosis infection is clearly influenced by factors such as
      nutrition, immune status, and both mycobacterial and host genetics, the variable
      pathogenesis of TB in infected individuals remains poorly understood. During the
      past two decades, it has become clear that the microbiota-the trillion organisms
      that reside at mucosal surfaces within and on the body-can exert a major
      influence on disease outcome through its effects on host innate and adaptive
      immune function and metabolism. This new recognition of the potentially
      pleiotropic participation of the microbiome in immune responses has raised the
      possibility that the microbiota may influence M. tuberculosis infection and/or
      disease. Similarly, treatment of TB may alter the healthy steady-state
      composition and function of the microbiome, possibly affecting treatment outcome
      in addition to other host physiological parameters. Herein, we review emerging
      evidence for how the microbiota may influence the transition points in the life
      cycle of TB infection, including (i) resistance to initial infection, (ii)
      initial infection to latent tuberculosis (LTBI), (iii) LTBI to reactivated
      disease, and (iv) treatment to cure. A major goal of this review is to frame
      questions to guide future scientific and clinical studies in this largely
      unexplored but increasingly important area of TB research.

PMID- 30228239
TI  - Genome-Wide Association Study Reveals Genetic Link between Diarrhea-Associated
      Entamoeba histolytica Infection and Inflammatory Bowel Disease.
AB  - Entamoeba histolytica is the etiologic agent of amebic dysentery, though clinical
      manifestation of infection is highly variable ranging from subclinical
      colonization to invasive disease. We hypothesize that host genetics contribute to
      the variable outcomes of E. histolytica infection; thus, we conducted a genome
      wide association study (GWAS) in two independent birth cohorts of Bangladeshi
      infants monitored for susceptibility to E. histolytica disease in the first year
      of life. Children with at least one diarrheal episode positive for E. histolytica
      (cases) were compared to children with no detectable E. histolytica infection in
      the same time frame (controls). Meta-analyses under a fixed-effect inverse
      variance weighting model identified multiple variants in a region of chromosome
      10 containing loci associated with symptomatic E. histolytica infection. An
      intergenic insertion between CREM and CCNY (rs58000832) achieved genome-wide
      significance (P value from meta-analysis [Pmeta] = 6.05 * 10-9), and each
      additional risk allele of rs58000832 conferred 2.42 increased odds of a diarrhea
      associated E. histolytica infection. The most strongly associated single
      nucleotide polymorphism (SNP) within a gene was in an intron of CREM (rs58468612;
      Pmeta = 8.94 * 10-8), which has been implicated as a susceptibility locus for
      inflammatory bowel disease (IBD). Gene expression resources suggest associated
      loci are related to the lower expression of CREM Increased CREM expression is
      also observed in early E. histolytica infection. Further, CREM-/- mice were more
      susceptible to E. histolytica amebic colitis. These genetic associations
      reinforce the pathological similarities observed in gut inflammation between E.
      histolytica infection and IBD.IMPORTANCE Diarrhea is the second leading cause of
      death for children globally, causing 760,000 deaths each year in children less
      than 5 years old. Amebic dysentery contributes significantly to this burden,
      especially in developing countries. The identification of host factors that
      control or enable enteric pathogens has the potential to transform our
      understanding of disease predisposition, outcomes, and treatments. Our discovery
      of the transcriptional regulator cAMP-responsive element modulator (CREM) as a
      genetic modifier of susceptibility to amebic disease has implications for
      understanding the pathogenesis of other diarrheal infections. Further, emerging
      evidence for CREM in IBD susceptibility suggests that CREM is a critical
      regulator of enteric inflammation and may have broad therapeutic potential as a
      drug target across intestinal inflammatory diseases.

PMID- 30228240
TI  - Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple
      Clinical Isolates of Nontypeable Haemophilus influenzae.
AB  - Biofilms play a critical role in the colonization, persistence, and pathogenesis
      of many human pathogens. Multiple mucosa-associated pathogens have evolved a
      mechanism of rapid adaptation, termed the phasevarion, which facilitates a
      coordinated regulation of numerous genes throughout the bacterial genome. This
      epigenetic regulation occurs via phase variation of a DNA methyltransferase, Mod.
      The phasevarion of nontypeable Haemophilus influenzae (NTHI) significantly
      affects the severity of experimental otitis media and regulates several disease
      related processes. However, the role of the NTHI phasevarion in biofilm formation
      is unclear. The present study shows that the phasevarions of multiple NTHI
      clinical isolates regulate in vitro biofilm formation under disease-specific
      microenvironmental conditions. The impact of phasevarion regulation was greatest
      under alkaline conditions that mimic those known to occur in the middle ear
      during disease. Under alkaline conditions, NTHI strains that express the ModA2
      methyltransferase formed biofilms with significantly greater biomass and less
      distinct architecture than those formed by a ModA2-deficient population. The
      biofilms formed by NTHI strains that express ModA2 also contained less
      extracellular DNA (eDNA) and significantly less extracellular HU, a DNABII DNA
      binding protein critical for biofilm structural stability. Stable biofilm
      structure is critical for bacterial pathogenesis and persistence in multiple
      experimental models of disease. These results identify a role for the phasevarion
      in regulation of biofilm formation, a process integral to the chronic nature of
      many infections. Understanding the role of the phasevarion in biofilm formation
      is critical to the development of prevention and treatment strategies for these
      chronic diseases.IMPORTANCE Upper respiratory tract infections are the number one
      reason for a child to visit the emergency department, and otitis media (middle
      ear infection) ranks third overall. Biofilms contribute significantly to the
      chronic nature of bacterial respiratory tract infections, including otitis media,
      and make these diseases particularly difficult to treat. Several mucosa
      associated human pathogens utilize a mechanism of rapid adaptation termed the
      phasevarion, or phasevariable regulon, to resist environmental and host immune
      pressures. In this study, we assessed the role of the phasevarion in regulation
      of biofilm formation by nontypeable Haemophilus influenzae (NTHI), which causes
      numerous respiratory tract diseases. We found that the NTHI phasevarion regulates
      biofilm structure and critical biofilm matrix components under disease-specific
      conditions. The findings of this work could be significant in the design of
      improved strategies against NTHI infections, as well as diseases due to other
      pathogens that utilize a phasevarion.

PMID- 30228242
TI  - Phosphorylation and Proteasome Recognition of the mRNA-Binding Protein Cth2
      Facilitates Yeast Adaptation to Iron Deficiency.
AB  - Iron is an indispensable micronutrient for all eukaryotic organisms due to its
      participation as a redox cofactor in many metabolic pathways. Iron imbalance
      leads to the most frequent human nutritional deficiency in the world. Adaptation
      to iron limitation requires a global reorganization of the cellular metabolism
      directed to prioritize iron utilization for essential processes. In response to
      iron scarcity, the conserved Saccharomyces cerevisiae mRNA-binding protein Cth2,
      which belongs to the tristetraprolin family of tandem zinc finger proteins,
      coordinates a global remodeling of the cellular metabolism by promoting the
      degradation of multiple mRNAs encoding highly iron-consuming proteins. In this
      work, we identify a critical mechanism for the degradation of Cth2 protein during
      the adaptation to iron deficiency. Phosphorylation of a patch of Cth2 serine
      residues within its amino-terminal region facilitates recognition by the SCFGrr1
      ubiquitin ligase complex, accelerating Cth2 turnover by the proteasome. When Cth2
      degradation is impaired by either mutagenesis of the Cth2 serine residues or
      deletion of GRR1, the levels of Cth2 rise and abrogate growth in iron-depleted
      conditions. Finally, we uncover that the casein kinase Hrr25 phosphorylates and
      promotes Cth2 destabilization. These results reveal a sophisticated
      posttranslational regulatory pathway necessary for the adaptation to iron
      depletion.IMPORTANCE Iron is a vital element for many metabolic pathways,
      including the synthesis of DNA and proteins, and the generation of energy via
      oxidative phosphorylation. Therefore, living organisms have developed tightly
      controlled mechanisms to properly distribute iron, since imbalances lead to
      nutritional deficiencies, multiple diseases, and vulnerability against pathogens.
      Saccharomyces cerevisiae Cth2 is a conserved mRNA-binding protein that
      coordinates a global reprogramming of iron metabolism in response to iron
      deficiency in order to optimize its utilization. Here we report that the
      phosphorylation of Cth2 at specific serine residues is essential to regulate the
      stability of the protein and adaptation to iron depletion. We identify the kinase
      and ubiquitination machinery implicated in this process to establish a
      posttranscriptional regulatory model. These results and recent findings for both
      mammals and plants reinforce the privileged position of E3 ubiquitin ligases and
      phosphorylation events in the regulation of eukaryotic iron homeostasis.

PMID- 30228244
TI  - The Multifunctional Fungal Ergosterol.
AB  - The roles of ergosterol in the regulation of membrane fluidity and structure, as
      well its role as a target for the activity of antifungals, have been known for
      decades. Two recent studies, however, demonstrated that ergosterol is an
      immunologically active lipid that induces pyroptosis and that virtually all steps
      of its biosynthetic process are potential drug targets. In combination, those two
      reports strongly indicate that the biological relevance of ergosterol is broader
      than the current literature suggests.

PMID- 30228243
TI  - The Mitochondrial Ca2+ Uniporter Complex (MCUC) of Trypanosoma brucei Is a Hetero
      oligomer That Contains Novel Subunits Essential for Ca2+ Uptake.
AB  - The mitochondrial calcium uniporter complex (MCUC) is a highly selective channel
      that conducts calcium ions across the organelle inner membrane. We previously
      characterized Trypanosoma brucei's MCU (TbMCU) as an essential component of the
      MCUC required for parasite viability and infectivity. In this study, we
      characterize its paralog T. brucei MCUb (TbMCUb) and report the identification of
      two novel components of the complex that we named TbMCUc and TbMCUd. These new
      MCUC proteins are unique and conserved only in trypanosomatids. In situ tagging
      and immunofluorescence microscopy revealed that they colocalize with TbMCU and
      TbMCUb to the mitochondria of T. brucei Blue Native PAGE and immunodetection
      analyses indicated that the MCUC proteins exist in a large protein complex with a
      molecular weight of approximately 380 kDa. RNA interference (RNAi) or
      overexpression of the TbMCUc and TbMCUd genes significantly reduced or enhanced
      mitochondrial Ca2+ uptake in T. brucei, respectively, without affecting the
      mitochondrial membrane potential, indicating that they are essential components
      of the MCUC of this parasite. The specific interactions of TbMCU with TbMCUb,
      TbMCUc, or TbMCUd were confirmed by coimmunoprecipitation and split-ubiquitin
      membrane-based yeast two-hybrid (MYTH) assays. Furthermore, combining mutagenesis
      analysis with MYTH assays revealed that transmembrane helices (TMHs) were
      determinant of the interactions between TbMCUC subunits. In summary, our study
      has identified two novel essential components of the MCUC of T. brucei and
      defined their direct physical interactions with the other subunits that result in
      a hetero-oligomeric MCUC.IMPORTANCETrypanosoma brucei causes human African
      trypanosomiasis and nagana in animals. The finding of a mitochondrial calcium
      uniporter (MCU) conserved in this parasite was essential for the discovery of the
      gene encoding the pore subunit. Mitochondrial Ca2+ transport mediated by the MUC
      complex is critical in Trypanosoma brucei for shaping the dynamics of cytosolic
      Ca2+ increases, for the bioenergetics of the cells, and for viability and
      infectivity. We found that one component of the complex (MCUb) does not act as a
      dominant negative effector of the channel as in vertebrate cells and that the
      TbMCUC possesses two unique subunits (MCUc and MCUd) present only in
      trypanosomatids and required for Ca2+ transport. The study of the interactions
      between these four subunits (MCU, MCUb, MCUc, and MCUd) by a variety of
      techniques that include coimmunoprecipitation, split-ubiquitin membrane-based
      yeast two-hybrid assays, and site-directed mutagenesis suggests that they
      interact through their transmembrane helices to form hetero-oligomers.

PMID- 30228241
TI  - Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine
      Candidate.
AB  - Glioblastoma (GBM) is the deadliest type of brain tumor, and glioma stem cells
      (GSCs) contribute to tumor recurrence and therapeutic resistance. Thus, an
      oncolytic virus targeting GSCs may be useful for improving GBM treatment. Because
      Zika virus (ZIKV) has an oncolytic tropism for infecting GSCs, we investigated
      the safety and efficacy of a live attenuated ZIKV vaccine candidate (ZIKV-LAV)
      for the treatment of human GBM in a GSC-derived orthotopic model. Intracerebral
      injection of ZIKV-LAV into mice caused no neurological symptoms or behavioral
      abnormalities. The neurovirulence of ZIKV-LAV was more attenuated than that of
      the licensed Japanese encephalitis virus LAV 14-14-2, underlining the superior
      safety of ZIKV-LAV for potential GBM treatment. Importantly, ZIKV-LAV
      significantly reduced intracerebral tumor growth and prolonged animal survival by
      selectively killing GSCs within the tumor. Mechanistically, ZIKV infection
      elicited antiviral immunity, inflammation, and GSC apoptosis. Together, these
      results further support the clinical development of ZIKV-LAV for GBM
      therapy.IMPORTANCE Glioblastoma (GBM), the deadliest type of brain tumor, is
      currently incurable because of its high recurrence rate after traditional
      treatments, including surgery to remove the main part of the tumor and radiation
      and chemotherapy to target residual tumor cells. These treatments fail mainly due
      to the presence of a cell subpopulation called glioma stem cells (GSCs), which
      are resistant to radiation and chemotherapy and capable of self-renewal and
      tumorigenicity. Because Zika virus (ZIKV) has an oncolytic tropism for infecting
      GSCs, we tested a live attenuated ZIKV vaccine candidate (ZIKV-LAV) for the
      treatment of human GBM in a human GSC-derived orthotopic model. Our results
      showed that ZIKV-LAV retained good efficacy against glioblastoma by selectively
      killing GSCs within the tumor. In addition, ZIKV-LAV exhibited an excellent
      safety profile upon intracerebral injection into the treated animals. The good
      balance between the safety of ZIKV-LAV and its efficacy against human GSCs
      suggests that it is a potential candidate for combination with the current
      treatment regimen for GBM therapy.

PMID- 30228245
TI  - Parental Vaccine Hesitancy and Declination of Influenza Vaccination Among
      Hospitalized Children.
AB  - OBJECTIVES: Parents frequently decline the influenza vaccine for their child
      during hospitalization. In this study, we aimed to assess the role of vaccine
      hesitancy in these declinations. METHODS: This cross-sectional survey study was
      conducted among English-speaking parents of influenza vaccine-eligible children
      who were hospitalized between October 2014 and April 2015. Between July 2015 and
      September 2015, parents were recruited via mail to complete the validated Parent
      Attitudes about Childhood Vaccines (PACV) survey (modified for influenza
      vaccination). PACV scores (0-100 scale) were dichotomized into scores of >=50
      (hesitant) and <50 (nonhesitant). The primary outcome was parental declination of
      the influenza vaccine for their child during hospitalization. A secondary outcome
      was the declination reason documented during hospitalization. The main
      independent variable was parental vaccine hesitancy status, determined by the
      PACV score. Multivariable logistic regression was used to examine the association
      between vaccine hesitancy and influenza vaccine declination, adjusting for
      sociodemographic, visit, and clinical characteristics. The relationship between
      vaccine hesitancy and declination reason was also explored. RESULTS: Of 199
      parents (18% response rate), 24% were vaccine hesitant and 53% declined the
      influenza vaccine for their child during hospitalization. Vaccine hesitancy
      (versus nonhesitancy) was associated with declining influenza vaccination
      (adjusted odds ratio: 6.4; 95% confidence interval: 2.5-16.5). The declination
      reason differed by vaccine hesitancy status, with a higher proportion of parents
      who were hesitant versus nonhesitant reporting "vaccine concern" or "vaccine
      unnecessary." CONCLUSIONS: Vaccine hesitancy was prevalent in this limited sample
      of parents of hospitalized children and associated with influenza vaccine
      declination. Additional investigation in a large, diverse, prospectively
      recruited cohort is warranted given the potential sampling bias present in this
      study.

PMID- 30228246
TI  - Toxicity of cancer therapy: what the cardiologist needs to know about
      angiogenesis inhibitors.
AB  - Clinical outcomes for patients with a wide range of malignancies have improved
      substantially over the last two decades. Tyrosine kinase inhibitors (TKIs) are
      potent signalling cascade inhibitors and have been responsible for significant
      advances in cancer therapy. By inhibiting vascular endothelial growth factor
      receptor (VEGFR)-mediated tumour blood vessel growth, VEGFR-TKIs have become a
      mainstay of treatment for a number of solid malignancies. However, the incidence
      of VEGFR-TKI-associated cardiovascular toxicity is substantial and previously
      under-recognised. Almost all patients have an acute rise in blood pressure, and
      the majority develop hypertension. They are associated with the development of
      left ventricular systolic dysfunction (LVSD), heart failure and myocardial
      ischaemia and can have effects on myocardial repolarisation. Attention should be
      given to rigorous baseline assessment of patients prior to commencing VEGFR-TKIs,
      with careful consideration of baseline cardiovascular risk factors. Baseline
      blood pressure measurement, ECG and cardiac imaging should be performed
      routinely. Hypertension management currently follows national guidelines, but
      there may be a future role forendothelin-1 antagonism in the prevention or
      treatment of VEGFR-TKI-associated hypertension. VEGFR-TKI-associated LVSD appears
      to be independent of dose and is reversible. Patients who develop LVSD and heart
      failure should be managed with conventional heart failure therapies, but the role
      of prophylactic therapy is yet to be defined. Serial monitoring of left
      ventricular function and QT interval require better standardisation and
      coordinated care. Management of these complex patients requires collaborative,
      cardio-oncology care to allow the true therapeutic potential from cancer
      treatment while minimising competing cardiovascular effects.

PMID- 30228247
TI  - Diagnostic accuracy and Bayesian analysis of new international ECG
      recommendations in paediatric athletes.
AB  - OBJECTIVE: Historically, electrocardiographic (ECG) interpretation criteria for
      athletes were only applicable to adults. New international recommendations now
      account for athletes <=16 years, but their clinical appropriateness is unknown.
      We sought to establish the diagnostic accuracy of new international ECG
      recommendations against the Seattle criteria and 2010 European Society of
      Cardiology (ESC) recommendations in paediatric athletes using receiver operator
      curve analysis. Clinical context was calculated using Bayesian analysis. METHODS:
      876 Arab and 428 black male paediatric athletes (11-18 years) were evaluated by
      medical questionnaire, physical examination, ECG and echocardiographic
      assessment. ECGs were retrospectively analysed according to the three criteria.
      RESULTS: Thirteen (1.0%) athletes were diagnosed with cardiac pathology that may
      predispose to sudden cardiac arrest/death (SCA/D) (8 (0.9%) Arab and (5 (1.2%)
      black)). Diagnostic accuracy was poor (0.68, 95% CI 0.54 to 0.82) for 2010 ESC
      recommendations, fair (0.70, 95% CI 0.54 to 0.85) for Seattle criteria and fair
      (0.77, 95% CI 0.61 to 0.93) for international recommendations. False-positive
      rates were 41.0% for 2010 ESC recommendations, 21.8% for Seattle criteria and
      6.8% for international recommendations. International recommendations provided a
      positive (+LR) and negative (-LR) post-test likelihood ratio of 9.0 (95% CI 5.1
      to 13.1) and 0.4 (95% CI 0.2 to 0.7), respectively. CONCLUSION: In Arab and black
      male paediatric athletes, new international recommendations outperform both the
      Seattle criteria and 2010 ESC recommendations, reducing false positive rates,
      while yielding a 'fair' diagnostic accuracy for cardiac pathology that may
      predispose to SCA/D. In clinical context, the 'chance' of detecting cardiac
      pathology within a paediatric male athlete with a positive ECG (+LR=9.0) was
      8.3%, whereas a negative ECG (-LR=0.4) was 0.4%.

PMID- 30228248
TI  - B-type natriuretic peptide, disease progression and clinical outcomes in atrial
      fibrillation.
AB  - OBJECTIVE: The association with B-type natriuretic peptide (BNP), disease
      progression and outcomes in patients with atrial fibrillation (AF) has not been
      thoroughly investigated. METHODS: We evaluated the association between BNP levels
      and outcomes, including AF progression, composite outcome of major adverse
      cardiovascular or neurological events (MACNE) and major bleeding, via pooled
      logistic regression and Cox frailty models in Outcomes Registry for Better
      Informed Treatment of Atrial Fibrillation II registry. AF progression was defined
      as either paroxysmal becoming persistent or permanent, or persistent becoming
      permanent at any follow-up. RESULTS: Among 13 375 patients with AF, 2797 with BNP
      values at baseline (median age (IQR), 72.0 (63.0-80.0) years; 43.0% women; median
      BNP, 238 (102-502) ng/L; 42.3% prior heart failure) were included in the models
      evaluating the association between BNP levels and MACNE or major bleeding. Of
      these, 1282 patients with paroxysmal or persistent AF at baseline were analysed
      in AF progression model. The likelihood of AF progression (adjusted OR, 1.11 for
      every 100 ng/mL; 95% CI 1.03 to 1.19) and MACNE (adjusted HR, 1.11 for every
      doubling in BNP values; 95% CI 1.01 to 1.22) increased with BNP concentration,
      while the elevated BNP values were not associated with increased risks of major
      bleeding. BNP values improved the risk prediction of AF progression and MACNE
      when added to conventional risk estimates. CONCLUSIONS: BNP levels are associated
      with increased risk of AF progression and cardiovascular outcomes in patients
      with AF. Further studies are required to assess whether biomarker-based risk
      stratification improves patient outcomes. CLINICAL TRIAL REGISTRATION:
      NCT01701817.

PMID- 30228250
TI  - Resistant hypertension in times of changing definitions and treatment
      recommendations.

PMID- 30228249
TI  - Cardiovascular imaging in Turner syndrome: state-of-the-art practice across the
      lifespan.
AB  - Cardiovascular imaging is essential to providing excellent clinical care for
      girls and women with Turner syndrome (TS). Congenital and acquired cardiovascular
      diseases are leading causes of the lifelong increased risk of premature death in
      TS. Non-invasive cardiovascular imaging is crucial for timely diagnosis and
      treatment planning, and a systematic and targeted imaging approach should combine
      echocardiography, cardiovascular magnetic resonance and, in select cases, cardiac
      CT. In recent decades, evidence has mounted for the need to perform
      cardiovascular imaging in all females with TS irrespective of karyotype and
      phenotype. This is due to the high incidence of outcome-determining lesions that
      often remain subclinical and occur in patterns specific to TS. This review
      provides an overview of state-of-the-art cardiovascular imaging practice in TS,
      by means of a review of the most recent literature, in the context of a recent
      consensus statement that has highlighted the role of cardiovascular diseases in
      these females.

PMID- 30228251
TI  - Accuracy of 24-hour ambulatory blood pressure monitoring by a novel cuffless
      device in clinical practice.
AB  - OBJECTIVE: Recently, a cuffless blood pressure (BP) measurement device using
      pulse transit time (PTT) for beat-to-beat calculation of BP values has been
      validated over a short time period. However, it remains unknown how values
      obtained with this device compare with standard ambulatory measurements over a 24
      hour period. We hypothesised that BP values measured by a cuffless PTT device
      (TestBP) are comparable with measurements by a standard upper arm cuff-based BP
      device (RefBP) in clinical practice over 24 hours. METHODS: Between May and
      December 2017, 71 individuals were prospectively included. Cuffless using the
      Somnotouch-NIBP (Somnomedics GmbH, Randersacker, Germany) and cuff-based standard
      24-hour BP measurements were performed simultaneously on the left and right arm,
      respectively. The first RefBP measurement was used as calibration measurement for
      the TestBP. RESULTS: Mean (+/-SD) age was 49.3 (15.1) years, and 51% were male.
      Mean 24-hour BP for TestBP and RefBP were 140.8 (20.0) versus 134.0 (17.3) mm Hg
      for systolic (p<0.0001) and 85.8 (14.1)versus79.3 (11.7) mm Hg for diastolic
      (p<0.0001) measurements, respectively. Mean absolute systolic and diastolic
      disagreements between TestBP and RefBP were 10.2 (7.2) and 8.2 (5.5) mm Hg,
      respectively. The number (percentage) of absolute differences between the mean 24
      hour BP values of the TestBP and RefBP within 5, 10 and 15 mm Hg were 23 (32.4),
      43 (60.6) and 54 (74.6) for systolic and 24 (33.8), 51 (71.8) and 65 (91.6) for
      diastolic measurements, respectively. CONCLUSION: In clinical practice over 24
      hours, there was a significant difference between the TestBP and RefBP with
      higher systolic and diastolic BP measured with the cuffless PTT device. Reasons
      for this difference need to be investigated. CLINICAL TRIAL REGISTRATION:
      NCT03054688; Results.

PMID- 30228252
TI  - Cochrane corner: inotropic agents and vasodilator strategies for cardiogenic
      shock or low cardiac output syndrome.

PMID- 30228253
TI  - Drainage of a Subphrenic Abscess Followed by Two-Stage Gastrectomy and Adjuvant
      Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Perforated Gastric
      Carcinoma: A Case Report.
AB  - BACKGROUND Perforated gastric cancer accounts for less than 1% of patients who
      present with an acute abdomen and for up to 16% of all gastric perforations. A
      two-stage laparoscopic procedure may be the therapeutic strategy of choice in
      selected patients, and adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC)
      can reduce the incidence of peritoneal recurrence. A rare case of subphrenic
      abscess and gastric perforation due to carcinoma of the gastric fundus, followed
      by two-stage gastrectomy and adjuvant HIPEC is presented. CASE REPORT A 65-year
      old man presented with a left subphrenic abscess secondary to perforated gastric
      carcinoma. Laparoscopic drainage of the abscess was performed. Ten days later,
      following recovery from sepsis, the patient underwent total laparoscopic
      gastrectomy, and adjuvant HIPEC followed by a Roux-en-Y esophagojejunostomy.
      Histopathology showed an intestinal-type gastric adenocarcinoma. The tumor was
      staged as pT4aN0. The postoperative course was uneventful except for transient
      atrial fibrillation. The patient was discharged home on postoperative day 11.
      Systemic adjuvant chemotherapy was begun one month later. At six-month follow-up,
      the patient had no discomfort on eating or any other symptoms. CONCLUSIONS In
      this case, a two-stage laparoscopic treatment for perforated gastric carcinoma
      combined with adjuvant HIPEC was feasible and safe and may be considered at the
      time of laparoscopic gastrectomy in selected patients with perforated gastric
      carcinoma.

PMID- 30228254
TI  - The Relationship Between Posterior Pituitary Bright Spot on Magnetic Resonance
      Imaging (MRI) and Postoperative Diabetes Insipidus for Pituitary Adenoma
      Patients.
AB  - BACKGROUND This study is to investigate the predictive value of posterior
      pituitary bright spot (PPBS) on magnetic resonance imaging (MRI) for
      postoperative diabetes insipidus (DI) in patients with pituitary adenoma.
      MATERIAL AND METHODS This was a retrospective study. In total, 65 patients with
      pituitary adenoma who underwent transsphenoidal surgery were enrolled. Before
      surgery, all patients had MRI examinations. The length of pituitary stalk and
      position of PPBS in T1WI sagittal and coronal sections were analyzed. The volume
      and height of the tumor was calculated in enhanced T1WI. Urine volume was
      monitored to analyze the clinical factors contributing to DI. RESULTS Among the
      65 cases of pituitary adenoma, there were 54 cases of positive PPBS and 11 cases
      of negative PPBS. There were 32 cases of transient DI, and among these, 22 cases
      were positive PPBS and 10 cases were negative PPBS. However, there were 33 cases
      without DI, and among these, 32 cases were positive PPBS and one case was
      negative PPBS. The negative PPBS was significantly higher in cases with DI,
      compared with positive PPBS (P<0.05). Logistic regression showed that
      preoperative negative PPBS was an important predictor for postoperative DI
      (P<0.05). CONCLUSIONS Postoperative DI should be considered when there is
      negative preoperative PPBS on MRI. Also, severe pituitary stalk compression
      indicates higher risk of postoperative DI.

PMID- 30228255
TI  - [Changes attributed to a program based on the action-training of health agents.
      What do the associations say?]
AB  - OBJECTIVE: Interventions aimed at improving health must take into account the
      health inequalities and the target the population in need. The mihsalud program
      (Women, Children and Men creating health) promotes health in vulnerable
      populations through engaging and collaborating with the local third sector. The
      objective of the study was to describe the changes attributed to the mihsalud
      programme and the process of action-training of community-based health volunteers
      (ASBC in Spanish) as perceived by the local organizations where they work or
      volunteer. METHODS: Qualitative descriptive study through semi-structured
      interviews with representatives of organizations that trained ASBC during 2012 in
      Valencia. Twelve semi-structured interviews were conducted with representatives
      of organizations which had trained some of their volunteers to become ASBC during
      the 2012 action-training session. The interviews were transcribed verbatim and
      analysed with the programme for qualitative analysis Nvivo. Themathic analysis
      was performed: transcripts were coded line by line from an inductive perspective.
      RESULTS: Three main categories were identified: 1) The role of the ASBC: The
      associations recognise the role of the ASBC among their peers and the importance
      of the training received in the program; 2) Perceived changes: The associations
      recognize having a broader vision of health, identify the role of the figure ASBC
      that coordinates with health professionals in their health area and networking
      with other associations that were previously unknown; 3) Challenges and
      opportunities: Lack of support for the continuity of projects with ASBC due to
      the precariousness of small organisations and coordination with services,
      recognition at the local level and promotion of participation and
      interculturality through ASBC and their peers. CONCLUSIONS: The organizations
      recognize that the program and ASBC have made collaboration with health sector
      possible, have promoted health among their peers and have encouraged networking
      with other organizations and areas.

PMID- 30228256
TI  - Transport evidence for a sliding two-dimensional quantum electron solid.
AB  - Ignited by the discovery of the metal-insulator transition, the behaviour of low
      disorder two-dimensional (2D) electron systems is currently the focus of a great
      deal of attention. In the strongly interacting limit, electrons are expected to
      crystallize into a quantum Wigner crystal, but no definitive evidence for this
      effect has been obtained despite much experimental effort over the years. Here,
      studying the insulating state of a 2D electron system in silicon, we have found
      two-threshold voltage-current characteristics with a dramatic increase in noise
      between the two threshold voltages. This behaviour cannot be described within
      existing traditional models. On the other hand, it is strikingly similar to that
      observed for the collective depinning of the vortex lattice in type-II
      superconductors. Adapting the model used for vortexes to the case of an electron
      solid yields good agreement with our experimental results, favouring the quantum
      electron solid as the origin of the low-density state.

PMID- 30228257
TI  - Paf1 and Ctr9 subcomplex formation is essential for Paf1 complex assembly and
      functional regulation.
AB  - The evolutionarily conserved multifunctional polymerase-associated factor 1
      (Paf1) complex (Paf1C), which is composed of at least five subunits (Paf1, Leo1,
      Ctr9, Cdc73, and Rtf1), plays vital roles in gene regulation and has connections
      to development and human diseases. Here, we report two structures of each of the
      human and yeast Ctr9/Paf1 subcomplexes, which assemble into heterodimers with
      very similar conformations, revealing an interface between the tetratricopeptide
      repeat module in Ctr9 and Paf1. The structure of the Ctr9/Paf1 subcomplex may
      provide mechanistic explanations for disease-associated mutations in human PAF1
      and CTR9. Our study reveals that the formation of the Ctr9/Paf1 heterodimer is
      required for the assembly of yeast Paf1C, and is essential for yeast viability.
      In addition, disruption of the interaction between Paf1 and Ctr9 greatly affects
      the level of histone H3 methylation in vivo. Collectively, our results shed light
      on Paf1C assembly and functional regulation.

PMID- 30228259
TI  - Biologically driven DOC release from peatlands during recovery from
      acidification.
AB  - Peatlands store 1/3 of global soil carbon, destabilisation of which contributes
      much to the recent increase in DOC (dissolved organic carbon) in freshwater
      ecosystems. One suggested mechanism for the enhanced decomposition of peat and
      the releases of DOC is recovery from acidification. However, no biological role
      in the process has yet been identified. Here we report extracellular enzyme
      activities and microbial composition in peatlands of Korea, the UK, Japan and
      Indonesia, and find higher pH to promote phenol oxidase activities, greater
      abundances in Actinobacteria and fungi, and enhanced pore-water DOC
      concentrations. Our pH manipulation experiments also showed that increase in pH
      enhanced phenol oxidase activity and DOC production with greater Actinobacterial
      and fungal abundances. Finally, knockout or addition of phenol oxidase
      dramatically changed DOC and phenolic production, indicating the central role of
      phenol oxidase in DOC mobilisation. Our findings provide evidence to support a
      previously unrecognized biological mechanism through which pH increases activate
      phenol oxidase, accelerating the release of DOC and phenolics.

PMID- 30228258
TI  - Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1
      axis.
AB  - Inflammatory bowel disease (IBD) are heterogenous disorders of the
      gastrointestinal tract caused by a spectrum of genetic and environmental factors.
      In mice, overlapping regions of chromosome 3 have been associated with
      susceptibility to IBD-like pathology, including a locus called Hiccs. However,
      the specific gene that controls disease susceptibility remains unknown. Here we
      identify a Hiccs locus gene, Alpk1 (encoding alpha kinase 1), as a potent
      regulator of intestinal inflammation. In response to infection with the commensal
      pathobiont Helicobacter hepaticus (Hh), Alpk1-deficient mice display exacerbated
      interleukin (IL)-12/IL-23 dependent colitis characterized by an enhanced
      Th1/interferon(IFN)-gamma response. Alpk1 controls intestinal immunity via the
      hematopoietic system and is highly expressed by mononuclear phagocytes. In
      response to Hh, Alpk1-/- macrophages produce abnormally high amounts of IL-12,
      but not IL-23. This study demonstrates that Alpk1 promotes intestinal
      homoeostasis by regulating the balance of type 1/type 17 immunity following
      microbial challenge.

PMID- 30228261
TI  - Saliva as a source of reagent to study human susceptibility to avian influenza
      H7N9 virus infection.
AB  - Avian influenza H7N9 viruses are an important public health concern due to their
      high mortality rate and potentials for future pandemics. We investigated human
      susceptibility to H7N9 viruses using recombinant H7N9 hemagglutinin (HA) proteins
      as a probe and found a strong association between H7N9 infections and HA binding
      among saliva samples from 32 patients and 60 uninfected controls in Jiangsu
      province, China, during the 2016 epidemic season. We also found that sialyl Lex
      (SLex) antigen that was recognized by H7N9 HA was associated with H7N9 virus
      infection. Further analysis suggested that additional saccharide residues
      adjacent to the SLex moiety may affect the H7N9-binding specificity. Our data
      suggested that saliva may be a useful reagent to study human susceptibility to
      avian influenza H7N9 virus, which may impact the disease control and prevention
      of avian influenza viruses as important human pathogens.

PMID- 30228262
TI  - Deep neural networks for accurate predictions of crystal stability.
AB  - Predicting the stability of crystals is one of the central problems in materials
      science. Today, density functional theory (DFT) calculations remain comparatively
      expensive and scale poorly with system size. Here we show that deep neural
      networks utilizing just two descriptors-the Pauling electronegativity and ionic
      radii-can predict the DFT formation energies of C3A2D3O12 garnets and ABO3
      perovskites with low mean absolute errors (MAEs) of 7-10 meV atom-1 and 20-34 meV
      atom-1, respectively, well within the limits of DFT accuracy. Further extension
      to mixed garnets and perovskites with little loss in accuracy can be achieved
      using a binary encoding scheme, addressing a critical gap in the extension of
      machine-learning models from fixed stoichiometry crystals to infinite universe of
      mixed-species crystals. Finally, we demonstrate the potential of these models to
      rapidly transverse vast chemical spaces to accurately identify stable
      compositions, accelerating the discovery of novel materials with potentially
      superior properties.

PMID- 30228260
TI  - A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate
      transcription at active genes.
AB  - Transcriptional regulation by chromatin is a highly dynamic process directed
      through the recruitment and coordinated action of epigenetic modifiers and
      readers of these modifications. Using an unbiased proteomic approach to find
      interactors of H3K36me3, a modification enriched on active chromatin, here we
      identify PWWP2A and HDAC2 among the top interactors. PWWP2A and its paralog
      PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not
      with MBD2/3, p66alpha/beta, and CHD3/4. PWWP2A competes with MBD3 for binding to
      MTA1, thus defining a new variant NuRD complex that is mutually exclusive with
      the MBD2/3 containing NuRD. In mESCs, PWWP2A/B is most enriched at highly
      transcribed genes. Loss of PWWP2A/B leads to increases in histone acetylation
      predominantly at highly expressed genes, accompanied by decreases in Pol II
      elongation. Collectively, these findings suggest a role for PWWP2A/B in
      regulating transcription through the fine-tuning of histone acetylation dynamics
      at actively transcribed genes.

PMID- 30228263
TI  - Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons
      and maintenance of spine curvature.
AB  - Defects in cerebrospinal fluid (CSF) flow may contribute to idiopathic scoliosis.
      However, the mechanisms underlying detection of CSF flow in the central canal of
      the spinal cord are unknown. Here we demonstrate that CSF flows bidirectionally
      along the antero-posterior axis in the central canal of zebrafish embryos. In the
      cfap298tm304 mutant, reduction of cilia motility slows transport posteriorly down
      the central canal and abolishes spontaneous activity of CSF-contacting neurons
      (CSF-cNs). Loss of the sensory Pkd2l1 channel nearly abolishes CSF-cN calcium
      activity and single channel opening. Recording from isolated CSF-cNs in vitro, we
      show that CSF-cNs are mechanosensory and require Pkd2l1 to respond to pressure.
      Additionally, adult pkd2l1 mutant zebrafish develop an exaggerated spine
      curvature, reminiscent of kyphosis in humans. These results indicate that CSF-cNs
      are mechanosensory cells whose Pkd2l1-driven spontaneous activity reflects CSF
      flow in vivo. Furthermore, Pkd2l1 in CSF-cNs contributes to maintenance of
      natural curvature of the spine.

PMID- 30228265
TI  - Combination of Gluten-Digesting Enzymes Improved Symptoms of Non-Celiac Gluten
      Sensitivity: A Randomized Single-blind, Placebo-controlled Crossover Study.
AB  - INTRODUCTION: Recently, the population of individuals with non-celiac gluten
      sensitivity (NCGS) who do not have celiac disease but show improved symptoms with
      a gluten-free diet, has increased. Enzyme replacement therapy using digestive
      enzymes is expected to improve the symptoms of NCGS and be sustainable, since
      gluten-related proteins that are indigestible by the digestive system have been
      considered triggers of NCGS. METHODS: We selected patients with NCGS by screening
      demographic interviews, as well as performing medical evaluations, anti-gluten
      antibody tests, and gluten challenge tests. We performed a single-blind and
      crossover clinical trial with these subjects using a gluten challenge with the
      enzyme mixture or a placebo. Our designed enzyme mixture contained peptidase,
      semi alkaline protease, deuterolysin, and cysteine protease derived from
      Aspergillus oryzae, Aspergillus melleus, Penicillium citrinum, and Carica papaya
      L., respectively. RESULTS: Administration of the enzyme mixture significantly
      decreased the change in the score of the symptom questionnaire before and after
      the gluten challenge compared with administration of the placebo in patients with
      NCGS without adverse events. In particular, the changes in the score of the
      gluten-induced incomplete evacuation feeling and headaches were significantly
      improved. The serum levels of interleukin (IL)-8, tumor necrosis factor (TNF)
      alpha, andregulated on activation, normal T cell expressed and secreted (RANTES)
      in subjects were not significantly changed by gluten, as expected from previous
      studies, and the enzyme mixture did not affect these inflammatory markers.
      CONCLUSION: In this human clinical study, we demonstrated the efficacy of the
      enzyme mixture derived from microorganisms and papaya in improving the symptoms
      of NCGS.

PMID- 30228264
TI  - Olfactory receptor OR2AT4 regulates human hair growth.
AB  - Olfactory receptors are expressed by different cell types throughout the body and
      regulate physiological cell functions beyond olfaction. In particular, the
      olfactory receptor OR2AT4 has been shown to stimulate keratinocyte proliferation
      in the skin. Here, we show that the epithelium of human hair follicles,
      particularly the outer root sheath, expresses OR2AT4, and that specific
      stimulation of OR2AT4 by a synthetic sandalwood odorant (Sandalore(r)) prolongs
      human hair growth ex vivo by decreasing apoptosis and increasing production of
      the anagen-prolonging growth factor IGF-1. In contrast, co-administration of the
      specific OR2AT4 antagonist Phenirat(r) and silencing of OR2AT4 inhibit hair
      growth. Together, our study identifies that human hair follicles can engage in
      olfactory receptor-dependent chemosensation and require OR2AT4-mediated signaling
      to sustain their growth, suggesting that olfactory receptors may serve as a
      target in hair loss therapy.

PMID- 30228268
TI  - Immune Checkpoint Inhibitor-Associated Colits and Hepatitis.
AB  - Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies that target
      downregulators of the anti-cancer immune response: cytotoxic T-lymphocyte antigen
      4, programmed cell death protein-1, and its ligand PD-L1. ICPIs are now approved
      for the treatment of a wide array of malignancies, with rates of durable
      responses in the metastatic setting far exceeding what would be expected from
      conventional chemotherapy. ICPIs have also been associated with rare but serious
      immune-related adverse events due to over-activation of the immune system that
      can affect any organ, including the gastrointestinal tract and liver. As the use
      of ICPIs in oncology continues to increase, ICPI-associated colitis and hepatitis
      will be encountered frequently by gastroenterologists and hepatologists. This
      review will focus on the diagnosis and management of ICPI-associated colitis and
      hepatitis. We will also compare these ICPI-related toxicities with sporadic
      inflammatory bowel disease and autoimmune liver disease.

PMID- 30228266
TI  - Nonhuman primates across sub-Saharan Africa are infected with the yaws bacterium
      Treponema pallidum subsp. pertenue.

PMID- 30228269
TI  - Implementation and benchmarking of a novel analytical framework to clinically
      evaluate tumor-specific fluorescent tracers.
AB  - During the last decade, the emerging field of molecular fluorescence imaging has
      led to the development of tumor-specific fluorescent tracers and an increase in
      early-phase clinical trials without having consensus on a standard methodology
      for evaluating an optical tracer. By combining multiple complementary state-of
      the-art clinical optical imaging techniques, we propose a novel analytical
      framework for the clinical translation and evaluation of tumor-targeted
      fluorescent tracers for molecular fluorescence imaging which can be used for a
      range of tumor types and with different optical tracers. Here we report the
      implementation of this analytical framework and demonstrate the tumor-specific
      targeting of escalating doses of the near-infrared fluorescent tracer bevacizumab
      800CW on a macroscopic and microscopic level. We subsequently demonstrate an 88%
      increase in the intraoperative detection rate of tumor-involved margins in
      primary breast cancer patients, indicating the clinical feasibility and support
      of future studies to evaluate the definitive clinical impact of fluorescence
      guided surgery.

PMID- 30228267
TI  - Targeting nonsense-mediated mRNA decay in colorectal cancers with microsatellite
      instability.
AB  - Nonsense-mediated mRNA decay (NMD) is responsible for the degradation of mRNAs
      with a premature termination codon (PTC). The role of this system in cancer is
      still quite poorly understood. In the present study, we evaluated the functional
      consequences of NMD activity in a subgroup of colorectal cancers (CRC)
      characterized by high levels of mRNAs with a PTC due to widespread instability in
      microsatellite sequences (MSI). In comparison to microsatellite stable (MSS) CRC,
      MSI CRC expressed increased levels of two critical activators of the NMD system,
      UPF1/2 and SMG1/6/7. Suppression of NMD activity led to the re-expression of
      dozens of PTC mRNAs. Amongst these, several encoded mutant proteins with putative
      deleterious activity against MSI tumorigenesis (e.g., HSP110DE9 chaperone
      mutant). Inhibition of NMD in vivo using amlexanox reduced MSI tumor growth, but
      not that of MSS tumors. These results suggest that inhibition of the oncogenic
      activity of NMD may be an effective strategy for the personalized treatment of
      MSI CRC.

PMID- 30228270
TI  - miR-1303 regulates BBB permeability and promotes CNS lesions following CA16
      infections by directly targeting MMP9.
AB  - Coxsackievirus A16 (CA16) is a member of the Picornaviridae family and causes
      mild and self-limiting hand, foot, and mouth disease (HFMD) in infants and young
      children. CA16 infection can also progress to central nervous system (CNS)
      complications; however, the underlying mechanism by which CA16 penetrates the
      blood-brain barrier (BBB) and then causes CNS damage remains unclear. This study
      aimed to explore the mechanism of CA16 neurotropic tropism by establishing an in
      vitro BBB model with CA16 infection and an in vivo CA16 rhesus monkey infant
      infection model. The results showed that CA16 infection induced increased
      permeability of the BBB accompanied by upregulation of matrix metalloproteinase 9
      (MMP9) expression. Subsequently, high-throughput miRNA sequencing technology and
      bioinformatics analysis revealed that miR-1303 may regulate BBB permeability by
      targeting MMP9. Next, we used dual-luciferase, qRT-PCR, and western blot assays
      to provide evidence of MMP9 targeting by miR-1303. Further experiments revealed
      that CA16 infection promoted the degradation of junctional complexes (Claudin4,
      Claudin5, VE-Cadherin, and ZO-1), likely by downregulating miR-1303 and
      upregulating MMP9. Finally, EGFP-CA16 infection could enter the CNS by
      facilitating the degradation of junctional complexes, eventually causing
      neuroinflammation and injury to the CNS, which was confirmed using the in vivo
      rhesus monkey model. Our results indicate that CA16 might penetrate the BBB and
      then enter the CNS by downregulating miR-1303, which disrupts junctional
      complexes by directly regulating MMP9 and ultimately causing pathological CNS
      changes. These results provide new therapeutic targets in HFMD patients following
      CA16 infection.

PMID- 30228272
TI  - Quantum theory cannot consistently describe the use of itself.
AB  - Quantum theory provides an extremely accurate description of fundamental
      processes in physics. It thus seems likely that the theory is applicable beyond
      the, mostly microscopic, domain in which it has been tested experimentally. Here,
      we propose a Gedankenexperiment to investigate the question whether quantum
      theory can, in principle, have universal validity. The idea is that, if the
      answer was yes, it must be possible to employ quantum theory to model complex
      systems that include agents who are themselves using quantum theory. Analysing
      the experiment under this presumption, we find that one agent, upon observing a
      particular measurement outcome, must conclude that another agent has predicted
      the opposite outcome with certainty. The agents' conclusions, although all
      derived within quantum theory, are thus inconsistent. This indicates that quantum
      theory cannot be extrapolated to complex systems, at least not in a
      straightforward manner.

PMID- 30228271
TI  - Evolution of gene knockout strains of E. coli reveal regulatory architectures
      governed by metabolism.
AB  - Biological regulatory network architectures are multi-scale in their function and
      can adaptively acquire new functions. Gene knockout (KO) experiments provide an
      established experimental approach not just for studying gene function, but also
      for unraveling regulatory networks in which a gene and its gene product are
      involved. Here we study the regulatory architecture of Escherichia coli K-12
      MG1655 by applying adaptive laboratory evolution (ALE) to metabolic gene KO
      strains. Multi-omic analysis reveal a common overall schema describing the
      process of adaptation whereby perturbations in metabolite concentrations lead
      regulatory networks to produce suboptimal states, whose function is subsequently
      altered and re-optimized through acquisition of mutations during ALE. These
      results indicate that metabolite levels, through metabolite-transcription factor
      interactions, have a dominant role in determining the function of a multi-scale
      regulatory architecture that has been molded by evolution.

PMID- 30228273
TI  - Macroscopic helical chirality and self-motion of hierarchical self-assemblies
      induced by enantiomeric small molecules.
AB  - Transfer of molecular chirality to supramolecular chirality at nanoscale and
      microscale by chemical self-assembly has been studied intensively for years.
      However, how such molecular chirality further transfers to the macroscale along
      the same path remains elusive. Here we reveal how the chirality from molecular
      level transfers to macroscopic level via self-assembly. We assemble a macrostripe
      using enantiomeric camphorsulfonic acid (CSA)-doped polyaniline with hierarchical
      order. The stripe can twist into a single-handed helical ribbon via helical self
      motion. A multi-scale chemo-mechanical model is used to elucidate the mechanism
      underlying its chirality transfer and induction. The molecular origin of this
      macroscopic helical chirality is verified. Results provide a comprehensive
      understanding of hierarchical chirality transfer and helical motion in self
      assembled materials and even their natural analogues. The stripe exhibits
      disparate actuation behaviour under stimuli of enantiomeric amines and
      integrating such chiral perception with helical self-motion may motivate chiral
      biomimetic studies of smart materials.

PMID- 30228274
TI  - Author Correction: Genome-wide mapping of plasma protein QTLs identifies
      putatively causal genes and pathways for cardiovascular disease.
AB  - In the originally published version of this Article, financial support was not
      fully acknowledged. The sentence "KS was supported by the 'Biomedical Research
      Program' funds at Weill Cornell Medicine in Qatar, a program funded by the Qatar
      Foundation" has been added to the acknowledgement section in both the PDF and
      HTML versions of the Article.

PMID- 30228276
TI  - Cultivated and wild Pleurotus ferulae ethanol extracts inhibit hepatocellular
      carcinoma cell growth via inducing endoplasmic reticulum stress- and mitochondria
      dependent apoptosis.
AB  - Pleurotus ferulae is a kind of editable mushroom and has various biological
      functions such as antitumor, antioxidation and immunoregulation. Wild P. ferulae
      was successfully domesticated but the antitumor function and mechanisms of
      cultivated and wild P. ferulae need to be compared and explored. Here, we
      prepared cultivated and wild P. ferulae ethanol extracts (PFEE-C and PFEE-W) and
      compared their antitumor effect on hepatocellular carcinoma. Our data showed that
      PFEE-C and PFEE-W significantly inhibited the growth of H22 and HepG2 cells
      through induction of apoptosis. PFEE-W exhibited higher antitumor activity than
      PFEE-C. Both PFEE-C and PFEE-W induced endoplasmic reticulum (ER) stress
      characterized by the up-regulated levels of phosphorylated JNK, cleaved caspase
      12 and HSP70, and mitochondrial dysfunction characterized by the reduction of
      mitochondrial membrane potential and the release of cytochrome c, which promoted
      the cleavage of caspase-3, -7, -9 and PARP. Moreover, PFEE-C and PFEE-W
      significantly increased ROS generation in H22 cells and suppressed H22 cell
      migration through reducing the levels of matrix metalloproteinase -2 and -9.
      Further, PFEE-C inhibited H22 tumor growth in mouse model and improved the
      survival of tumor mice. These results indicated that PFEE-C and PFEE-W could
      inhibit hepatocellular carcinoma cell growth through ER stress- and mitochondria
      dependent apoptotic pathways.

PMID- 30228275
TI  - A high throughput screen for next-generation leads targeting malaria parasite
      transmission.
AB  - Spread of parasite resistance to artemisinin threatens current frontline
      antimalarial therapies, highlighting the need for new drugs with alternative
      modes of action. Since only 0.2-1% of asexual parasites differentiate into
      sexual, transmission-competent forms, targeting this natural bottleneck provides
      a tangible route to interrupt disease transmission and mitigate resistance
      selection. Here we present a high-throughput screen of gametogenesis against a
      ~70,000 compound diversity library, identifying seventeen drug-like molecules
      that target transmission. Hit molecules possess varied activity profiles
      including male-specific, dual acting male-female and dual-asexual-sexual, with
      one promising N-((4-hydroxychroman-4-yl)methyl)-sulphonamide scaffold found to
      have sub-micromolar activity in vitro and in vivo efficacy. Development of leads
      with modes of action focussed on the sexual stages of malaria parasite
      development provide a previously unexplored base from which future therapeutics
      can be developed, capable of preventing parasite transmission through the
      population.

PMID- 30228277
TI  - In-situ cross-linking strategy for efficient and operationally stable
      methylammoniun lead iodide solar cells.
AB  - Long-term operational stability is the foremost issue delaying the
      commercialization of perovskite solar cells (PSCs). Here we demonstrate an in
      situ cross-linking strategy for operationally stable inverted MAPbI3 PSCs through
      the incorporation of a cross-linkable organic small molecule additive
      trimethylolpropane triacrylate (TMTA) into perovskite films. TMTA can chemically
      anchor to grain boundaries and then in-situ cross-link to a robust continuous
      network polymer after thermal treatment, thus enhancing the thermal, water
      resisting and light-resisting properties of organic/perovskite films. As a
      result, the cross-linked PSCs exhibit 590-fold improvement in operational
      stability, retaining nearly 80% of their initial efficiency after continuous
      power output for 400 h at maximum power point under full-sun AM 1.5 G
      illumination of Xenon lamp without any UV-filter. In addition, under moisture or
      thermal (85  degrees C) conditions, cross-linked TMTA-based PSCs also show
      excellent stability with over 90% of their initial or post burn-in efficiency
      after aging for over 1000 h.

PMID- 30228278
TI  - Solvatochromic covalent organic frameworks.
AB  - Covalent organic frameworks (COFs) are an emerging class of highly tuneable
      crystalline, porous materials. Here we report the first COFs that change their
      electronic structure reversibly depending on the surrounding atmosphere. These
      COFs can act as solid-state supramolecular solvatochromic sensors that show a
      strong colour change when exposed to humidity or solvent vapours, dependent on
      vapour concentration and solvent polarity. The excellent accessibility of the
      pores in vertically oriented films results in ultrafast response times below 200
      ms, outperforming commercially available humidity sensors by more than an order
      of magnitude. Employing a solvatochromic COF film as a vapour-sensitive light
      filter, we demonstrate a fast humidity sensor with full reversibility and
      stability over at least 4000 cycles. Considering their immense chemical diversity
      and modular design, COFs with fine-tuned solvatochromic properties could broaden
      the range of possible applications for these materials in sensing and
      optoelectronics.

PMID- 30228279
TI  - Large muscles are beneficial but not required for improving thermogenic capacity
      in small birds.
AB  - It is generally assumed that small birds improve their shivering heat production
      capacity by developing the size of their pectoralis muscles. However, some
      studies have reported an enhancement of thermogenic capacity in the absence of
      muscle mass variation between seasons or thermal treatments. We tested the
      hypothesis that an increase in muscle mass is not a prerequisite for improving
      avian thermogenic capacity. We measured basal (BMR) and summit (Msum) metabolic
      rates of black capped chickadees (Poecile atricapillus) acclimated to
      thermoneutral (27  degrees C) and cold (-10  degrees C) temperatures and obtained
      body composition data from dissections. Cold acclimated birds consumed 44% more
      food, and had 5% and 20% higher BMR and Msum, respectively, compared to
      individuals kept at thermoneutrality. However, lean dry pectoralis and total
      muscle mass did not differ between treatments, confirming that the improvement of
      thermogenic capacity did not require an increase in skeletal muscle mass.
      Nevertheless, within temperature treatments, Msum was positively correlated with
      the mass of all measured muscles, including the pectoralis. Therefore, for a
      given acclimation temperature individuals with large muscles do benefit from
      muscle size in term of heat production but improving thermogenic capacity during
      cold acclimation likely requires an upregulation of cell functions.

PMID- 30228280
TI  - The Shape of Native Plant Cellulose Microfibrils.
AB  - Determining the shape of plant cellulose microfibrils is critical for
      understanding plant cell wall molecular architecture and conversion of cellulose
      into biofuels. Only recently has it been determined that these cellulose
      microfibrils are composed of 18 cellulose chains rather than 36 polymers arranged
      in a diamond-shaped pattern. This study uses density functional theory
      calculations to model three possible habits for the 18-chain microfibril and
      compares the calculated energies, structures, 13C NMR chemical shifts and WAXS
      diffractograms of each to evaluate which shape is most probable. Each model is
      capable of reproducing experimentally-observed data to some extent, but based on
      relative theoretical energies and reasonable reproduction of all variables
      considered, a microfibril based on 5 layers in a 34443 arrangement is predicted
      to be the most probable. A habit based on a 234432 arrangement is slightly less
      favored, and a 6 * 3 arrangement is considered improbable.

PMID- 30228281
TI  - Aqueous mounting media increasing tissue translucence improve image quality in
      Structured Illumination Microscopy of thick biological specimen.
AB  - Structured Illumination Microscopy (SIM) is a super-resolution microscopy method
      that has significantly advanced studies of cellular structures. It relies on
      projection of illumination patterns onto a fluorescently labelled biological
      sample. The information derived from the sample is then shifted to a detectable
      band, and in the process of image calculation in Fourier space the resolution is
      doubled. Refractive index homogeneity along the optical path is crucial to
      maintain a highly modulated illumination pattern necessary for high-quality SIM.
      This applies in particular to thick samples consisting of large cells and
      tissues. Surprisingly, sample mounting media for SIM have not undergone a
      significant evolution for almost a decade. Through identification and systematic
      evaluation of a number of non-hazardous, water-soluble chemical components of
      mounting media, we demonstrate an unprecedented improvement in SIM-image quality.
      Mounting solutions presented in this research are capable of reducing abundant
      light scattering which constitutes the limiting factor in 3D-SIM imaging of large
      Hodgkin's lymphoma and embryonic stem cells as well as 10 um tissue sections.
      Moreover, we demonstrate usefulness of some of the media in single molecule
      localisation microscopy. The results presented here are of importance for
      standardisation of 3D-SIM data acquisition pipelines for an expanding community
      of users.

PMID- 30228283
TI  - Author Correction: Computational Analysis of the Molecular Mechanism of RamR
      Mutations Contributing to Antimicrobial Resistance in Salmonella enterica.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30228284
TI  - Author Correction: Long-range non-diffusive spin transfer in a Hall insulator.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30228282
TI  - Analysis of gut microbiota profiles and microbe-disease associations in children
      with autism spectrum disorders in China.
AB  - Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders.
      Recent studies reported that children with ASD have altered gut microbiota
      profiles compared with typical development (TD) children. However, few studies on
      gut bacteria of children with ASD have been conducted in China. Here, in order to
      elucidate changes of fecal microbiota in children with ASD, 16S rRNA sequencing
      was conducted and the 16S rRNA (V3-V4) gene tags were amplified. We investigated
      differences in fecal microbiota between 35 children with ASD and 6 TD children.
      At the phylum level, the fecal microbiota of ASD group indicated a significant
      increase of the Bacteroidetes/Firmicutes ratio. At the genus level, we found that
      the relative abundance of Sutterella, Odoribacter and Butyricimonas was much more
      abundant in the ASD group whereas the abundance of Veillonella and Streptococcus
      was decreased significantly compared to the control group. Functional analysis
      demonstrated that butyrate and lactate producers were less abundant in the ASD
      group. In addition, we downloaded the association data set of microbe-disease
      from human microbe-disease association database and constructed a human disease
      network including ASD using our gut microbiome results. In this microbe-disease
      network based on microbe similarity of diseases, we found that ASD is positively
      correlated with periodontal, negatively related to type 1 diabetes. Therefore,
      these results suggest that microbe-based disease analysis is able to predict
      novel connection between ASD and other diseases and may play a role in revealing
      the pathogenesis of ASD.

PMID- 30228285
TI  - The added value of online user-generated content in traditional methods for
      influenza surveillance.
AB  - There has been considerable work in evaluating the efficacy of using online data
      for health surveillance. Often comparisons with baseline data involve various
      squared error and correlation metrics. While useful, these overlook a variety of
      other factors important to public health bodies considering the adoption of such
      methods. In this paper, a proposed surveillance system that incorporates models
      based on recent research efforts is evaluated in terms of its added value for
      influenza surveillance at Public Health England. The system comprises of two
      supervised learning approaches trained on influenza-like illness (ILI) rates
      provided by the Royal College of General Practitioners (RCGP) and produces ILI
      estimates using Twitter posts or Google search queries. RCGP ILI rates for
      different age groups and laboratory confirmed cases by influenza type are used to
      evaluate the models with a particular focus on predicting the onset, overall
      intensity, peak activity and duration of the 2015/16 influenza season. We show
      that the Twitter-based models perform poorly and hypothesise that this is mostly
      due to the sparsity of the data available and a limited training period.
      Conversely, the Google-based model provides accurate estimates with timeliness of
      approximately one week and has the potential to complement current surveillance
      systems.

PMID- 30228286
TI  - Knock-down of AHCY and depletion of adenosine induces DNA damage and cell cycle
      arrest.
AB  - Recently, functional connections between S-adenosylhomocysteine hydrolase (AHCY)
      activity and cancer have been reported. As the properties of AHCY include the
      hydrolysis of S-adenosylhomocysteine and maintenance of the cellular methylation
      potential, the connection between AHCY and cancer is not obvious. The mechanisms
      by which AHCY influences the cell cycle or cell proliferation have not yet been
      confirmed. To elucidate AHCY-driven cancer-specific mechanisms, we pursued a
      multi-omics approach to investigate the effect of AHCY-knockdown on
      hepatocellular carcinoma cells. Here, we show that reduced AHCY activity causes
      adenosine depletion with activation of the DNA damage response (DDR), leading to
      cell cycle arrest, a decreased proliferation rate and DNA damage. The underlying
      mechanism behind these effects might be applicable to cancer types that have
      either significant levels of endogenous AHCY and/or are dependent on high
      concentrations of adenosine in their microenvironments. Thus, adenosine
      monitoring might be used as a preventive measure in liver disease, whereas
      induced adenosine depletion might be the desired approach for provoking the DDR
      in diagnosed cancer, thus opening new avenues for targeted therapy. Additionally,
      including AHCY in mutational screens as a potential risk factor may be a
      beneficial preventive measure.

PMID- 30228287
TI  - Psoralen induced cell cycle arrest by modulating Wnt/beta-catenin pathway in
      breast cancer cells.
AB  - Psoralen could inhibit the proliferation of human breast cancer cells, however,
      the molecular mechanism was unclear. We evaluated the anti-proliferative effects
      of psoralen by MTT, plate colony formation assay and cell cycle analysis in MCF-7
      and MDA-MB-231 cells. The effects of psoralen on activation of Wnt/beta-catenin
      and the related target genes were examined by quantitative real-time PCR, western
      blotting and cell immunofluorescence. The tumor growth was conducted in BALB/c
      nude mice and the pathological changes of heart, liver and kidney were also
      observed. Our results demonstrate that psoralen significantly inhibited cell
      proliferation by inducing G0/G1 phase arrest in MCF-7 cells and G2/M phase arrest
      in MDA-MB-231 cells. The expression of Fra-1 was reduced and Axin2 was promoted
      both in MCF-7 and MDA-MB-231 cells after psoralen treatment. The cytoplasmic
      accumulation and nuclear translocation of beta-catenin were significantly reduced
      by psoralen. Psoralen increased the levels of phospho-(Y142) beta-catenin, while
      decreased the expression of total beta-catenin and its downstream target Fra-1 in
      vitro and vivo. Moreover, psoralen didn't cause any significant toxicity at the
      effective concentration. Overall, our results might provide theoretical basis for
      clinical application of psoralen in breast cancer.

PMID- 30228288
TI  - Association between resistin and fibroblast growth factor 23 in patients with
      type 2 diabetes mellitus.
AB  - Fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease and
      all-cause mortality in patients with diabetes mellitus. Insulin resistance has
      recently been reported to increase FGF23 levels, and resistin is a peptide that
      mainly regulates insulin resistance. However, few studies have investigated the
      association between FGF23 and resistin. A total of 422 patients with diabetes
      mellitus were recruited for this cross-sectional study to examine the association
      between resistin and intact FGF23. The mean ( +/- standard deviation) age was
      63.1 +/- 11.9 years, and the median HbA1c was 6.7% (range, 6.1-7.1%). The mean
      estimated glomerular filtration rate (eGFR) was 66.2 +/- 23.1 mL/min/m2. Multiple
      regression analysis for resistin showed that logFGF23 (coefficient (Coef): 1.551;
      standard error (SE): 0.739; P = 0.036), C-peptide (Coef: 0.798; SE: 0.229; P =
      0.001), ghrelin (Coef: 1.061; SE: 0.332; P = 0.001), intact parathyroid hormone
      (Coef: 0.022; SE: 0.099; P = 0.030), and eGFR (Coef: -0.091; SE: 0.017; P <
      0.001) were all significantly associated with the resistin level. These
      associations were modified in patients with higher age, lower body mass index,
      and higher vitamin D levels. These results suggest that resistin is positively
      associated with serum FGF23 levels.

PMID- 30228289
TI  - Publisher Correction: Lower body mass index and mortality in older adults
      starting dialysis.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30228290
TI  - Heritability of obsessive-compulsive trait dimensions in youth from the general
      population.
AB  - Obsessive-compulsive disorder (OCD) is a heritable childhood-onset psychiatric
      disorder that may represent the extreme of obsessive-compulsive (OC) traits that
      are widespread in the general population. We report the heritability of the
      Toronto Obsessive-Compulsive Scale (TOCS), a new measure designed to assess the
      complete range of OC traits in youth. We also examined the dimensional nature of
      the TOCS and the degree to which genetic effects are unique or shared between
      dimensions. OC traits were measured using the TOCS in 16,718 youth (6-18 years)
      at a science museum. We conducted a factor analysis to identify OC trait
      dimensions. We used univariate and multivariate twin models to estimate the
      heritability of OC trait dimensions in a subset of twins (220 pairs). Six OC
      dimensions were identified: Cleaning/Contamination, Symmetry/Ordering,
      Rumination, Superstition, Counting/Checking, and Hoarding. The TOCS total score
      (74%) and each OC dimension was heritable (30-77%). Hoarding was not highly
      correlated with other OC dimensions, but did share genetic effects. Shared
      genetics accounted for most of the shared variance among dimensions, whereas
      unique environment accounted for the majority of dimension-specific variance. One
      exception was Hoarding, which had considerable unique genetic factors. A latent
      trait did not account for the shared variance between dimensions. In conclusion,
      OC traits and individual OC dimensions were heritable, although the degree of
      shared and dimension-specific etiological factors varied by dimension. The TOCS
      may be informative for genetic research of OC traits in youth. Genetic research
      of OC traits should consider both OC dimension and total trait scores.

PMID- 30228291
TI  - Nanoparticle-based Chemiluminescence for Chiral Discrimination of Thiol
      Containing Amino Acids.
AB  - The ability to recognize the molecular chirality of enantiomers is extremely
      important owing to their critical role in drug development and biochemistry.
      Convenient discrimination of enantiomers has remained a challenge due to lack of
      unsophisticated methods. In this work, we have reported a simple strategy for
      chiral recognition of thiol-containing amino acids including penicillamine (PA),
      and cysteine (Cys). We have successfully designed a nanoparticle-based
      chemiluminescence (CL) system based on the reaction between cadmium telluride
      quantum dots (CdTe QDs) and the enantiomers. The different interactions of CdTe
      QDs with PA enantiomers or Cys enantiomers led to different CL intensities,
      resulting in the chiral recognition of these enantiomers. The developed method
      showed the ability for determination of enantiomeric excess of PA and Cys. It has
      also obtained an enantioselective concentration range from 1.15 to 9.2 mM for PA.
      To demonstrate the potential application of this method, the designed platform
      was applied for the quantification of PA in urine and tablet samples. For the
      first time, we presented a novel practical application of nanoparticle-based CL
      system for chiral discrimination.

PMID- 30228292
TI  - SIRT1 activation attenuates alpha cell hyperplasia, hyperglucagonaemia and
      hyperglycaemia in STZ-diabetic mice.
AB  - The NAD+-dependent lysine deacetylase, Sirtuin 1 (SIRT1), plays a central role in
      metabolic regulation. With type 1 diabetes a disease that is characterised by
      metabolic dysregulation, we sought to assess the impact of SIRT1 activation in
      experimental, streptozotocin (STZ)-induced diabetes. CD1 mice with and without
      STZ-induced diabetes were randomized to receive the SIRT1 activating compound,
      SRT3025, or vehicle over 20 weeks. Vehicle treated STZ-CD1 mice developed severe
      hyperglycaemia with near-absent circulating insulin and widespread beta cell loss
      in association with hyperglucagonaemia and expanded islet alpha cell mass.
      Without affecting beta-cell mass or circulating insulin, diabetic mice that
      received SRT3025 had substantially improved glycaemic control with greatly
      reduced islet alpha cell mass and lower plasma glucagon concentrations.
      Consistent with reduced glucagon abundance, the diabetes-associated
      overexpression of key gluconeogenic enzymes, glucose-6-phosphatase and PEPCK were
      also lowered by SRT3025. Incubating cultured alpha cells with SRT3025 diminished
      their glucagon secretion and proliferative activity in association with a
      reduction in the alpha cell associated transcription factor, Aristaless Related
      Homeobox (Arx). By reducing the paradoxical increase in glucagon, SIRT1
      activation may offer a new, alpha-cell centric approach to the treatment of type
      1 diabetes.

PMID- 30228293
TI  - Isolated hallucination is less predictive than thought disorder in psychosis:
      Insight from a longitudinal study in a clinical population at high risk for
      psychosis.
AB  - Perceptual abnormalities (PAs) such as auditory hallucinations are one of the
      most common symptoms of psychotic patients. However, it remains unclear whether
      symptoms of sub-clinical PAs also play a key role in predicting psychosis. In an
      ongoing prospective follow-up study of individuals at a clinical high risk (CHR)
      of psychosis, we evaluated the potential of first-time experience of PAs and/or
      thought content disorders (TCDs) to predict psychosis. Conversion to psychosis
      was the major focus of this follow-up study. A total of 511 CHRs were recruited,
      of whom 443 (86.7%) completed the clinical follow-up of at least 6 months and up
      to 2 years. CHRs were divided into four groups according to the presence of PAs
      and/or TCDs. At the follow-up endpoint, 39 (19.9%) CHRs in the "TCDs-only" group,
      2 (8.3%) in the "PAs-only" group, 45 (17.0%) in the "TCDs-and-PAs" group, and 1
      (3.8%) in the "None" group converted to psychosis. Survival analysis revealed a
      higher conversion rate in CHRs with TCDs compared with those with PAs only. CHRs
      with isolated PAs had shown a higher level of dysphoric mood at baseline compared
      with those with TCDs. About 89% TCDs contents were related with their experienced
      PAs. Compared with TCDs, the isolated PAs are not strongly associated with
      increased susceptibility to psychosis.

PMID- 30228294
TI  - Two-copy Quantum Teleportation.
AB  - We investigate two-copy scenario of quantum teleportation based on Bell
      measurements. The detailed protocol is presented and the general expression of
      the corresponding optimal teleportation fidelity is derived, which is given by
      the two-copy fully entangled fraction that is invariant under local unitary
      transformations. We prove that under a specific case of the protocol, which is
      significant for improving the optimal fidelity, the set of states with their two
      copy fully entangled fractions bounded by a threshold value that required for
      useful two-copy teleportation is convex and compact. Hence the witness operators
      exist to separate states that are useful for two-copy teleportation from the rest
      ones. Moreover, we show that the optimal fidelity of two-copy teleportation
      surpasses that of the original one copy teleportation.

PMID- 30228295
TI  - Progress and potential in organoid research.
AB  - Tissue and organ biology are very challenging to study in mammals, and progress
      can be hindered, particularly in humans, by sample accessibility and ethical
      concerns. However, advances in stem cell culture have made it possible to derive
      in vitro 3D tissues called organoids, which capture some of the key
      multicellular, anatomical and even functional hallmarks of real organs at the
      micrometre to millimetre scale. Recent studies have demonstrated that organoids
      can be used to model organ development and disease and have a wide range of
      applications in basic research, drug discovery and regenerative medicine.
      Researchers are now beginning to take inspiration from other fields, such as
      bioengineering, to generate organoids that are more physiologically relevant and
      more amenable to real-life applications.

PMID- 30228298
TI  - Publisher Correction: Heme enables proper positioning of Drosha and DGCR8 on
      primary microRNAs.
AB  - The original version of this Article contained an error in Fig. 1. In panel d,
      the model on the right of the panel was incorrectly labeled '+Heme', and should
      have read '- Heme'. This has now been corrected in both the PDF and HTML versions
      of the Article.

PMID- 30228296
TI  - Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy
      resistance.
AB  - Expression of the chromatin-associated protein HMGA2 correlates with progression,
      metastasis and therapy resistance in pancreatic ductal adenocarcinoma (PDAC).
      Hmga2 has also been identified as a marker of a transient subpopulation of PDAC
      cells that has increased metastatic ability. Here, we characterize the
      requirement for Hmga2 during growth, dissemination, and metastasis of PDAC in
      vivo using conditional inactivation of Hmga2 in well-established autochthonous
      mouse models of PDAC. Overall survival, primary tumour burden, presence of
      disseminated tumour cells in the peritoneal cavity or circulating tumour cells in
      the blood, and presence and number of metastases were not significantly different
      between mice with Hmga2-wildtype or Hmga2-deficient tumours. Treatment of mice
      with Hmga2-wildtype and Hmga2-deficient tumours with gemcitabine did not uncover
      a significant impact of Hmga2-deficiency on gemcitabine sensitivity. Hmga1 and
      Hmga2 overlap in their expression in both human and murine PDAC, however
      knockdown of Hmga1 in Hmga2-deficient cancer cells also did not decrease
      metastatic ability. Thus, Hmga2 remains a prognostic marker which identifies a
      metastatic cancer cell state in primary PDAC, however Hmga2 has limited if any
      direct functional impact on PDAC progression and therapy resistance.

PMID- 30228297
TI  - Residence time of singlet oxygen in membranes.
AB  - Photodynamic therapy uses photosensitizers (PS) to kill cancer cells by
      generating reactive oxygen species - like singlet oxygen (SO) - upon illumination
      with visible light. PS membrane anchoring augments local SO concentration, which
      in turn increases photodynamic efficiency. The latter may suffer from SO's escape
      into the aqueous solution or premature quenching. Here we determined the time
      constants of SO escape and quenching by target molecules to be in the nanosecond
      range, the former being threefold longer. We confined PS and dipolar target
      molecules either to different membrane monolayers or to the same leaflet and
      assessed their abundance by fluorescence correlation spectroscopy or membrane
      surface potential measurements. The rate at which the contribution of the dipolar
      target molecules to membrane dipole potential vanished, served as a measure of
      the photo-oxidation rate. The solution of the reaction-diffusion equations did
      not indicate diffusional rate limitations. Nevertheless, reducing the PS-target
      distance increased photodynamic efficiency by preventing other SO susceptible
      moieties from protecting the target. Importantly, our analytical model revealed a
      fourfold difference between SO generation rates per molecule of the two used PSs.
      Such analysis of PS quantum yield in a membrane environment may help in designing
      better PSs.

PMID- 30228299
TI  - Toward high-fidelity coherent electron spin transport in a GaAs double quantum
      dot.
AB  - In this paper, we investigate how to achieve high-fidelity electron spin
      transport in a GaAs double quantum dot. Our study examines fidelity loss in spin
      transport from multiple perspectives. We first study incoherent fidelity loss due
      to hyperfine and spin-orbit interaction. We calculate fidelity loss due to the
      random Overhauser field from hyperfine interaction, and spin relaxation rate due
      to spin-orbit interaction in a wide range of experimental parameters with a focus
      on the occurrence of spin hot spots. A safe parameter regime is identified in
      order to avoid these spin hot spots. We then analyze systematic errors due to non
      adiabatic transitions in the Landau-Zener process of sweeping the interdot
      detuning, and propose a scheme to take advantage of possible Landau-Zener
      Stuckelberg interference to achieve high-fidelity spin transport at a higher
      speed. At last, we study another systematic error caused by the correction to the
      electron g-factor from the double dot potential, which can lead to a notable
      phase error. In all, our results should provide a useful guidance for future
      experiments on coherent electron spin transport.

PMID- 30228300
TI  - Multilayer graphene shows intrinsic resistance peaks in the carrier density
      dependence.
AB  - Since the advent of graphene, a variety of studies have been performed to
      elucidate its fundamental physics, or to explore its practical applications. Gate
      tunable resistance is one of the most important properties of graphene and has
      been studied in 1-3 layer graphene in a number of efforts to control the band gap
      to obtain a large on-off ratio. On the other hand, the transport property of
      multilayer graphene with more than three layers is less well understood. Here we
      show a new aspect of multilayer graphene. We found that four-layer graphene shows
      intrinsic peak structures in the gate voltage dependence of its resistance at
      zero magnetic field. Measurement of quantum oscillations in magnetic field
      confirmed that the peaks originate from the specific band structure of graphene
      and appear at the carrier density for the bottoms of conduction bands and valence
      bands. The intrinsic peak structures should generally be observed in AB-stacked
      multilayer graphene. The present results would be significant for understanding
      the physics of graphene and making graphene FET devices.

PMID- 30228301
TI  - Stem cell fate in cancer growth, progression and therapy resistance.
AB  - Although we have come a long way in our understanding of the signals that drive
      cancer growth, and how these signals can be targeted, effective control of this
      disease remains a key scientific and medical challenge. The therapy resistance
      and relapse that are commonly seen are driven in large part by the inherent
      heterogeneity within cancers that allows drugs to effectively eliminate some, but
      not all, malignant cells. Here, we focus on the fundamental drivers of this
      heterogeneity by examining emerging evidence that shows that these traits are
      often controlled by the disruption of normal cell fate and aberrant adoption of
      stem cell signals. We discuss how undifferentiated cells are preferentially
      primed for transformation and often serve as the cell of origin for cancers. We
      also consider evidence showing that activation of stem cell programmes in cancers
      can lead to progression, therapy resistance and metastatic growth and that
      targeting these attributes may enable better control over a difficult disease.

PMID- 30228303
TI  - Cryptic introgression: evidence that selection and plasticity mask the full
      phenotypic potential of domesticated Atlantic salmon in the wild.
AB  - Domesticated Atlantic salmon grow much faster than wild salmon when reared
      together in fish tanks under farming conditions (size ratios typically 1:2-3). In
      contrast, domesticated salmon only display marginally higher growth than wild
      salmon when reared together in rivers (size ratios typically 1:1-1.2). This begs
      the question why? Is this a difference in the plastic response driven by
      divergent energy budgets between the two environments, or is it a result of
      selection, whereby domesticated salmon that display the greatest growth-potential
      are those at greatest risk of mortality in the wild? We reared domesticated,
      hybrid and wild salmon in a river until they smoltified at age 2 or 4, and
      thereafter in fish tanks for a further 2 years. In the river, there was no
      difference in the mean size between the groups. In contrast, after being
      transferred from the river to fish tanks, the domesticated salmon significantly
      outgrew the wild salmon (maximum size ratio of ~1:1.8). This demonstrates that
      selection alone cannot be responsible for the lack of growth differences observed
      between domesticated and wild salmon in rivers. Nevertheless, the final size
      ratios observed after rearing in tanks were lower than expected in that
      environment, thus suggesting that plasticity, as for selection, cannot be the
      sole mechanism. We therefore conclude that a combination of energy-budget
      plasticity, and selection via growth-potential mortality, cause the differences
      in growth reaction norms between domesticated and wild salmon across these
      contrasting environments. Our results imply that if phenotypic changes are not
      observed in wild populations following introgression of domesticated
      conspecifics, it does not mean that functional genetic changes have not occurred
      in the admixed population. Clearly, under the right environmental conditions, the
      underlying genetic changes will manifest themselves in the phenotype.

PMID- 30228302
TI  - A high content, small molecule screen identifies candidate molecular pathways
      that regulate rod photoreceptor outer segment renewal.
AB  - The outer segment of the vertebrate rod photoreceptor is a highly modified cilium
      composed of many discrete membranous discs that are filled with the protein
      machinery necessary for phototransduction. The unique outer segment structure is
      renewed daily with growth at the base of the outer segment where new discs are
      formed and shedding at the distal end where old discs are phagocytized by the
      retinal pigment epithelium. In order to understand how outer segment renewal is
      regulated to maintain outer segment length and function, we used a small molecule
      screening approach with the transgenic (hsp70:HA-mCherryTM) zebrafish, which
      expresses a genetically-encoded marker of outer segment renewal. We identified
      compounds with known bioactivity that affect five content areas: outer segment
      growth, outer segment shedding, clearance of shed outer segment tips, Rhodopsin
      mislocalization, and differentiation at the ciliary marginal zone. Signaling
      pathways that are targeted by the identified compounds include cyclooxygenase in
      outer segment growth, gamma-Secretase in outer segment shedding, and mTor in RPE
      phagocytosis. The data generated by this screen provides a foundation for further
      investigation of the signaling pathways that regulate photoreceptor outer segment
      renewal.

PMID- 30228304
TI  - 3D multiscale imaging of human vocal folds using synchrotron X-ray
      microtomography in phase retrieval mode.
AB  - Human vocal folds possess outstanding abilities to endure large, reversible
      deformations and to vibrate up to more than thousand cycles per second. This
      unique performance mainly results from their complex specific 3D and multiscale
      structure, which is very difficult to investigate experimentally and still
      presents challenges using either confocal microscopy, MRI or X-ray
      microtomography in absorption mode. To circumvent these difficulties, we used
      high-resolution synchrotron X-ray microtomography with phase retrieval and report
      the first ex vivo 3D images of human vocal-fold tissues at multiple scales.
      Various relevant descriptors of structure were extracted from the images:
      geometry of vocal folds at rest or in a stretched phonatory-like position, shape
      and size of their layered fibrous architectures, orientation, shape and size of
      the muscle fibres as well as the set of collagen and elastin fibre bundles
      constituting these layers. The developed methodology opens a promising insight
      into voice biomechanics, which will allow further assessment of the
      micromechanics of the vocal folds and their vibratory properties. This will then
      provide valuable guidelines for the design of new mimetic biomaterials for the
      next generation of artificial larynges.

PMID- 30228305
TI  - Connexin 26 Expression in Mammalian Cardiomyocytes.
AB  - Connexins are a family of membrane-spanning proteins named according to their
      molecular weight. They are known to form membrane channels mediating cell-cell
      communication, which play an essential role in the propagation of electrical
      activity in the heart. Cx26 has been described in a number of tissues but not in
      the heart, and its mutations are frequently associated with deafness and skin
      diseases. The aim of this study was to assess the possible Cx26 expression in
      heart tissues of different mammalian species and to demonstrate its localization
      at level of cardiomyocytes. Samples of pig, human and rat heart and H9c2 cells
      were used for our research. Immunohistochemical and molecular biology techniques
      were employed to test the expression of Cx26. Interestingly, this connexin was
      found in cardiomyocytes, at level of clusters scattered over the cell cytoplasm
      but not at level of the intercalated discs where the other cardiac connexins are
      usually located. Furthermore, the expression of Cx26 in H9c2 myoblast cells
      increased when they were differentiated into cardiac-like phenotype. To our
      knowledge, the expression of Cx26 in pig, human and rat has been demonstrated for
      the first time in the present paper.

PMID- 30228307
TI  - Proteome analysis reveals a role of rainbow trout lymphoid organs during Yersinia
      ruckeri infection process.
AB  - Yersinia ruckeri is the causative agent of enteric redmouth disease in salmonids.
      Head kidney and spleen are major lymphoid organs of the teleost fish where
      antigen presentation and immune defense against microbes take place. We
      investigated proteome alteration in head kidney and spleen of the rainbow trout
      following Y. ruckeri strains infection. Organs were analyzed after 3, 9 and 28
      days post exposure with a shotgun proteomic approach. GO annotation and protein
      protein interaction were predicted using bioinformatic tools. Thirty four
      proteins from head kidney and 85 proteins from spleen were found to be
      differentially expressed in rainbow trout during the Y. ruckeri infection
      process. These included lysosomal, antioxidant, metalloproteinase, cytoskeleton,
      tetraspanin, cathepsin B and c-type lectin receptor proteins. The findings of
      this study regarding the immune response at the protein level offer new insight
      into the systemic response to Y. ruckeri infection in rainbow trout. This
      proteomic data facilitate a better understanding of host-pathogen interactions
      and response of fish against Y. ruckeri biotype 1 and 2 strains. Protein-protein
      interaction analysis predicts carbon metabolism, ribosome and phagosome pathways
      in spleen of infected fish, which might be useful in understanding biological
      processes and further studies in the direction of pathways.

PMID- 30228308
TI  - Water printing of ferroelectric polarization.
AB  - Ferroelectrics, which generate a switchable electric field across the solid
      liquid interface, may provide a platform to control chemical reactions (physical
      properties) using physical fields (chemical stimuli). However, it is challenging
      to in-situ control such polarization-induced interfacial chemical structure and
      electric field. Here, we report that construction of chemical bonds at the
      surface of ferroelectric BiFeO3 in aqueous solution leads to a reversible bulk
      polarization switching. Combining piezoresponse (electrostatic) force microscopy,
      X-ray photoelectron spectroscopy, scanning transmission electron microscopy,
      first-principles calculations and phase-field simulations, we discover that the
      reversible polarization switching is ascribed to the sufficient formation of
      polarization-selective chemical bonds at its surface, which decreases the
      interfacial chemical energy. Therefore, the bulk electrostatic energy can be
      effectively tuned by H+/OH- concentration. This water-induced ferroelectric
      switching allows us to construct large-scale type-printing of polarization using
      green energy and opens up new opportunities for sensing, high-efficient
      catalysis, and data storage.

PMID- 30228306
TI  - 15d-PGJ2-loaded nanocapsules ameliorate experimental gout arthritis by reducing
      pain and inflammation in a PPAR-gamma-sensitive manner in mice.
AB  - Gout arthritis (GA) is a painful inflammatory disease in response to monosodium
      urate (MSU) crystals in the joints. 15deoxy-Delta12,14-prostaglandin J2 (15d
      PGJ2) is a natural activator of PPAR-gamma with analgesic, anti-inflammatory, and
      pro-resolution properties. Thus, we aimed to evaluate the effect and mechanisms
      of action of 15d-PGJ2 nanocapsules (NC) in the model of GA in mice, since a
      reduction of 33-fold in the dose of 15d-PGJ2 has been reported. Mice were treated
      with 15d-PGJ2-loaded NC, inert NC, free 15d-PGJ2 (without NC), or 15d-PGJ2-loaded
      NC+ GW9662, a PPAR-gamma inhibitor. We show that 15d-PGJ2-loaded NC provided
      analgesic effect in a dose that the free 15d-PGJ2 failed to inhibiting pain and
      inflammation. Hence, 15d-PGJ2-loaded NC reduced MSU-induced IL-1beta, TNF-alpha,
      IL-6, IL-17, and IL-33 release and oxidative stress. Also, 15d-PGJ2-loaded NC
      decreased the maturation of IL-1beta in LPS-primed BMDM triggered by MSU.
      Further, 15d-PGJ2-loaded NC decreased the expression of the components of the
      inflammasome Nlrp3, Asc, and Pro-caspase-1, as consequence of inhibiting NF
      kappaB activation. All effects were PPAR-gamma-sensitive. Therefore, we
      demonstrated that 15d-PGJ2-loaded NC present analgesic and anti-inflammatory
      properties in a PPAR-gamma-dependent manner inhibiting IL-1beta release and NF
      kappaB activation in GA. Concluding, 15d-PGJ2-loaded NC ameliorates MSU-induced
      GA in a PPAR-gamma-sensitive manner.

PMID- 30228309
TI  - Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a
      bicyclic thymine analogue.
AB  - Fluorescent base analogues (FBAs) have emerged as a powerful class of molecular
      reporters of location and environment for nucleic acids. In our overall mission
      to develop bright and useful FBAs for all natural nucleobases, herein we describe
      the synthesis and thorough characterization of bicyclic thymidine (bT), both as a
      monomer and when incorporated into DNA. We have developed a robust synthetic
      route for the preparation of the bT DNA monomer and the corresponding protected
      phosphoramidite for solid-phase DNA synthesis. The bT deoxyribonucleoside has a
      brightness value of 790 M-1cm-1 in water, which is comparable or higher than most
      fluorescent thymine analogues reported. When incorporated into DNA, bT pairs
      selectively with adenine without perturbing the B-form structure, keeping the
      melting thermodynamics of the B-form duplex DNA virtually unchanged. As for most
      fluorescent base analogues, the emission of bT is reduced inside DNA (4.5- and 13
      fold in single- and double-stranded DNA, respectively). Overall, these properties
      make bT an interesting thymine analogue for studying DNA and an excellent
      starting point for the development of brighter bT derivatives.

PMID- 30228312
TI  - Cleaner shrimp are a sustainable option to treat parasitic disease in farmed
      fish.
AB  - Chemical use is widespread in aquaculture to treat parasitic diseases in farmed
      fish. Cleaner fish biocontrols are increasingly used in fish farming as an
      alternative to medicines. However, cleaner fish are susceptible to some of their
      clients' parasites and their supply is largely dependent on wild harvest. In
      comparison, cleaner shrimp are not susceptible to fish ectoparasites and they can
      be reliably bred in captivity. The effectiveness of shrimp in reducing parasites
      on farmed fish remained unexplored until now. We tested four cleaner shrimp
      species for their ability to reduce three harmful parasites (a monogenean fluke,
      a ciliate protozoan, and a leech) on a farmed grouper. All shrimp reduced
      parasites on fish and most reduced the free-living early-life environmental
      stages - a function not provided by cleaner fish. Cleaner shrimp are sustainable
      biocontrol candidates against parasites of farmed fish, with the peppermint
      cleaner shrimp reducing parasites by up to 98%.

PMID- 30228310
TI  - Artemisinin kills malaria parasites by damaging proteins and inhibiting the
      proteasome.
AB  - Artemisinin and its derivatives (collectively referred to as ARTs) rapidly reduce
      the parasite burden in Plasmodium falciparum infections, and antimalarial control
      is highly dependent on ART combination therapies (ACTs). Decreased sensitivity to
      ARTs is emerging, making it critically important to understand the mechanism of
      action of ARTs. Here we demonstrate that dihydroartemisinin (DHA), the clinically
      relevant ART, kills parasites via a two-pronged mechanism, causing protein
      damage, and compromising parasite proteasome function. The consequent
      accumulation of proteasome substrates, i.e., unfolded/damaged and
      polyubiquitinated proteins, activates the ER stress response and underpins DHA
      mediated killing. Specific inhibitors of the proteasome cause a similar build-up
      of polyubiquitinated proteins, leading to parasite killing. Blocking protein
      synthesis with a translation inhibitor or inhibiting the ubiquitin-activating
      enzyme, E1, reduces the level of damaged, polyubiquitinated proteins, alleviates
      the stress response, and dramatically antagonizes DHA activity.

PMID- 30228311
TI  - Reduction in the levels of CoQ biosynthetic proteins is related to an increase in
      lifespan without evidence of hepatic mitohormesis.
AB  - Mitohormesis is an adaptive response induced by a mild mitochondrial stress that
      promotes longevity and metabolic health in different organisms. This mechanism
      has been proposed as the cause of the increase in the survival in Coq7+/-
      (Mclk1+/-) mice, which show hepatic reduction of COQ7, early mitochondrial
      dysfunction and increased oxidative stress. Our study shows that the lack of COQ9
      in Coq9Q95X mice triggers the reduction of COQ7, COQ6 and COQ5, which results in
      an increase in life expectancy. However, our results reveal that the hepatic CoQ
      levels are not decreased and, therefore, neither mitochondrial dysfunction or
      increased oxidative stress are observed in liver of Coq9Q95X mice. These data
      point out the tissue specific differences in CoQ biosynthesis. Moreover, our
      results suggest that the effect of reduced levels of COQ7 on the increased
      survival in Coq9Q95X mice may be due to mitochondrial mechanisms in non-liver
      tissues or to other unknown mechanisms.

PMID- 30228313
TI  - The effect of the heart rate lowering drug Ivabradine on hemodynamics in
      atherosclerotic mice.
AB  - The heart rate lowering drug Ivabradine was shown to improve cardiac outcome in
      patients with previous heart failure. However, in patients without heart failure,
      no beneficial effect of Ivabradine was observed. Animal studies suggested a
      preventive effect of Ivabradine on atherosclerosis which was due to an increase
      in wall shear stress (WSS), the blood flow-induced frictional force exerted on
      the endothelium, triggering anti-inflammatory responses. However, data on the
      effect of Ivabradine on WSS is sparse. We aim to study the effect of Ivabradine
      on (i) the 3D WSS distribution over a growing plaque and (ii) plaque composition.
      We induced atherosclerosis in ApoE-/- mice by placing a tapered cast around the
      right common carotid artery (RCCA). Five weeks after cast placement, Ivabradine
      was administered via drinking water (15 mg/kg/day) for 2 weeks, after which the
      RCCA was excised for histology analyses. Before and after Ivabradine treatment,
      animals were imaged with Doppler Ultrasound to measure blood velocity. Vessel
      geometry was obtained using contrast-enhanced micro-CT. Time-averaged WSS during
      systole, diastole and peak WSS was subsequently computed. Ivabradine
      significantly decreased heart rate (459 +/- 28 bpm vs. 567 +/- 32 bpm, p <
      0.001). Normalized peak flow significantly increased in the Ivabradine group
      (124.2% +/- 40.5% vs. 87.3% +/- 25.4%, p < 0.05), reflected by an increased
      normalized WSS level during systole (110.7% +/- 18.4% vs. 75.4% +/- 24.6%, p <
      0.05). However, plaque size or composition including plaque area, relative
      necrotic core area and macrophage content were not altered in mice treated with
      Ivabradine compared to controls. We conclude that increased WSS in response to
      Ivabradine treatment did not affect plaque progression in a murine model.

PMID- 30228314
TI  - Control of coordinatively unsaturated Zr sites in ZrO2 for efficient C-H bond
      activation.
AB  - Due to the complexity of heterogeneous catalysts, identification of active sites
      and the ways for their experimental design are not inherently straightforward but
      important for tailored catalyst preparation. The present study reveals the active
      sites for efficient C-H bond activation in C1-C4 alkanes over ZrO2 free of any
      metals or metal oxides usually catalysing this reaction. Quantum chemical
      calculations suggest that two Zr cations located at an oxygen vacancy are
      responsible for the homolytic C-H bond dissociation. This pathway differs from
      that reported for other metal oxides used for alkane activation, where metal
      cation and neighbouring lattice oxygen form the active site. The concentration of
      anion vacancies in ZrO2 can be controlled through adjusting the crystallite size.
      Accordingly designed ZrO2 shows industrially relevant activity and durability in
      non-oxidative propane dehydrogenation and performs superior to state-of-the-art
      catalysts possessing Pt, CrOx, GaOx or VOx species.

PMID- 30228315
TI  - Serum miR-331-3p predicts tumor recurrence in esophageal adenocarcinoma.
AB  - MicroRNAs (miRNAs) may contribute to the initiation and progression of cancer.
      The role of circulating miRNAs as predictors of recurrence in esophageal
      adenocarcinoma (EAC) has not been extensively explored. Here we measured the
      expressions of 167 miRNAs in serum samples from a discovery cohort of 72 EAC
      patients (32 patients with recurrence and 40 patients without). A rank sum test
      was performed to identify differentially expressed miRNAs. Cox regression model
      was applied to estimate the effect of miRNA expression on recurrence-free
      survival. The eligible miRNAs were then validated in an independent cohort of 329
      EAC patients (132 patients with recurrence and 197 patients without). miR-331-3p
      was identified and confirmed to be differentially expressed between EAC patients
      with and without recurrence and associated with recurrence-free survival. In both
      cohorts, the expression of miR-331-3p was consistently decreased in patients with
      recurrence compared to those without (P < 0.05). Using patients with low
      expression of miR-331-3p as reference, those with high expression had HRs for
      recurrence of 0.45 (95% CI, 0.21-0.96, P = 0.040) and 0.55 (95% CI, 0.38-0.78, P
      = 0.001) in the discovery and validation cohorts, respectively. Therefore, serum
      miR-331-3p may be a useful biomarker for identifying EAC patients at high risk of
      recurrence.

PMID- 30228316
TI  - Preconditioners for the geometry optimisation and saddle point search of
      molecular systems.
AB  - A class of preconditioners is introduced to enhance geometry optimisation and
      transition state search of molecular systems. We start from the Hessian of
      molecular mechanical terms, decompose it and retain only its positive definite
      part to construct a sparse preconditioner matrix. The construction requires only
      the computation of the gradient of the corresponding molecular mechanical terms
      that are already available in popular force field software packages. For
      molecular crystals, the preconditioner can be combined straightforwardly with the
      exponential preconditioner recently introduced for periodic systems. The
      efficiency is demonstrated on several systems using empirical, semiempirical and
      ab initio potential energy surfaces.

PMID- 30228317
TI  - Neurobiology of male sexual dysfunctions in psychiatric disorders: the cases of
      depression, anxiety, mania and schizophrenia.
AB  - While the pathophysiology of several psychiatric disorders has become modestly
      elucidated in the last decade, comorbid sexual dysfunctions in such patients are
      frequently left apart from clinical and research interest. We aimed to address
      the malfunctioning neurocircuitry underlying sexual dysfunctions in depression,
      anxiety, schizophrenia and mania. We performed a comprehensive literature review,
      addressing any combination of the topics of "neurobiology"/"neural",
      "sexual"/"desire"/"arousal"/"orgasm"/"ejaculation" and
      "depression"/"anxiety"/"schizophrenia"/"mania"/"bipolar". Altered
      neurotransmitter levels or connectivity in patients are reported in sexual
      dysfunctions (either desire, arousal, orgasm and ejaculation) and main
      psychiatric disorders (depression, anxiety, mania and schizophrenia). Neuronal
      pathways responsible for the occurrence of sexual dysfunctions in psychiatric
      disorders can be  figured out by overlap  of their acknowledged pathophysiology.
      However, specific research in that group is scant, so future tailored studies are
      warranted to elucidate actual mechanisms.

PMID- 30228318
TI  - Correction: The clinical spectrum and natural history of early-onset diseases due
      to DNA polymerase gamma mutations.
AB  - Since the online publication of the article, the authors have noted errors with
      Table 2; this has now been corrected in both the HTML and the PDF.

PMID- 30228325
TI  - AI helps unlock 'dark matter' of bizarre superconductors.

PMID- 30228321
TI  - The hidden lives of deep-sea creatures caught on camera.

PMID- 30228326
TI  - Stand back, Aquaman: Harpoon-throwing satellite takes aim at space junk.

PMID- 30228328
TI  - Australia has no climate-change policy - again.

PMID- 30228329
TI  - From the archive.

PMID- 30228331
TI  - A history of substance.

PMID- 30228332
TI  - How female scientists can confront gender bias in the workplace.

PMID- 30228333
TI  - Clever chemistry offers new source of jet fuel.

PMID- 30228334
TI  - Huge peer-review study reveals lack of women and non-Westerners.

PMID- 30228336
TI  - Enhanced ANGPTL2 expression in adipose tissues and its association with insulin
      resistance in obese women.
AB  - Angiopoietin-like protein 2 has been proposed to be a key mediator linking
      obesity and insulin resistance. However, no detailed study of ANGPTL2 expression
      in human adipose tissues has yet been reported. To investigate the pattern and
      regulation of ANGPTL2 expression in human adipose tissues in obesity and its
      related diseases, we recruited 32 non-diabetic and 13 type 2 diabetic obese women
      and 32 normal-weight women. ANGPTL2 mRNA was expressed at a similar level in
      visceral and subcutaneous adipose tissues. Adipose tissue ANGPTL2 mRNA was much
      higher in obese patients. Adipose tissue ANGPTL2 mRNA and serum ANGPTL2 levels
      showed strong associations with metabolic parameters associated with insulin
      resistance. In adipose tissue, ANGPTL2 mRNA was closely correlated with the
      expression of genes involved in inflammation and ER stress. ANGPTL2 mRNA was
      principally expressed in adipocytes, and its expression was markedly higher in
      the adipocyte but non-adipocyte fraction of obese adipose tissues. Culture of
      human adipocytes under conditions mimicking the microenvironment of obese adipose
      tissue (especially, increased ER stress) stimulated ANGPTL2 gene expression and
      secretion. In addition, co-culture of adipocytes and macrophages suggested that
      ANGPTL2 excessively produced by adipocytes, may contribute inflammation and
      remodeling in obese adipose tissues, thereby promoting insulin resistance.

PMID- 30228335
TI  - Wide-Field Functional Microscopy of Peripheral Nerve Injury and Regeneration.
AB  - Severe peripheral nerve injuries often result in partial repair and lifelong
      disabilities in patients. New surgical techniques and better graft tissues are
      being studied to accelerate regeneration and improve functional recovery.
      Currently, limited tools are available to provide in vivo monitoring of changes
      in nerve physiology such as myelination and vascularization, and this has impeded
      the development of new therapeutic options. We have developed a wide-field and
      label-free functional microscopy platform based on angiographic and vectorial
      birefringence methods in optical coherence tomography (OCT). By incorporating the
      directionality of the birefringence, which was neglected in the previously
      reported polarization-sensitive OCT techniques for nerve imaging, vectorial
      birefringence contrast reveals internal nerve microanatomy and allows for
      quantification of local myelination with superior sensitivity. Advanced OCT
      angiography is applied in parallel to image the three-dimensional vascular
      networks within the nerve over wide-fields. Furthermore, by combining vectorial
      birefringence and angiography, intraneural vessels can be discriminated from
      those of the surrounding tissues. The technique is used to provide longitudinal
      imaging of myelination and revascularization in the rodent sciatic nerve model,
      i.e. imaged at certain sequential time-points during regeneration. The animals
      were exposed to either crush or transection injuries, and in the case of
      transection, were repaired using an autologous nerve graft or acellular nerve
      allograft. Such label-free functional imaging by the platform can provide new
      insights into the mechanisms that limit regeneration and functional recovery, and
      may ultimately provide intraoperative assessment in human subjects.

PMID- 30228337
TI  - Seasonal and spatial variability of the partial pressure of carbon dioxide in the
      human-impacted Seine River in France.
AB  - Carbon evasion from rivers is an important component of the global carbon cycle.
      The intensification of anthropogenic pressures on hydrosystems requires studies
      of human-impacted rivers to identify and quantify the main drivers of carbon
      evasion. In 2016 and 2017, four field campaigns were conducted in the Seine River
      network characterized by an intensively cropped and highly populated basin. We
      measured partial pressures of carbon dioxide (pCO2) in streams or rivers draining
      land under different uses at different seasons. We also computed pCO2 from an
      existing data set (pH, water temperature and total alkalinity) going back until
      1970. Here we report factors controlling pCO2 that operate at different time and
      space scales. In our study, the Seine River was shown to be supersaturated in CO2
      with respect to the atmospheric equilibrium, as well as a source of CO2. Our
      results suggest an increase in pCO2 from winter to summer in small streams
      draining forests (from 1670 to 2480 ppm), croplands (from 1010 to 1550 ppm), and
      at the outlet of the basin (from 2490 to 3630 ppm). The main driver of pCO2 was
      shown to be dissolved organic carbon (DOC) concentrations (R2 = 0.56, n = 119, p
      < 0.05) that are modulated by hydro-climatic conditions and groundwater
      discharges. DOC sources were linked to land use and soil, mainly leaching into
      small upstream streams, but also to organic pollution, mainly found downstream in
      larger rivers. Our long-term analysis of the main stream suggests that pCO2
      closely mirrors the pattern of urban water pollution over time. These results
      suggest that factors controlling pCO2 operate differently upstream and downstream
      depending on the physical characteristics of the river basin and on the intensity
      and location of the main anthropogenic pressures. The influence of these
      controlling factors may also differ over time, according to the seasons, and
      mirror long term changes in these anthropogenic pressures.

PMID- 30228338
TI  - Probing Limits of Information Spread with Sequential Seeding.
AB  - We consider here information spread which propagates with certain probability
      from nodes just activated to their not yet activated neighbors. Diffusion
      cascades can be triggered by activation of even a small set of nodes. Such
      activation is commonly performed in a single stage. A novel approach based on
      sequential seeding is analyzed here resulting in three fundamental contributions.
      First, we propose a coordinated execution of randomized choices to enable precise
      comparison of different algorithms in general. We apply it here when the newly
      activated nodes at each stage of spreading attempt to activate their neighbors.
      Then, we present a formal proof that sequential seeding delivers at least as good
      spread coverage as the single stage seeding does. Moreover, we also show that,
      under modest assumptions, sequential seeding performs provably better than the
      single stage seeding using the same number of seeds and node ranking. Finally, we
      present experimental results comparing single stage and sequential approaches on
      directed and undirected graphs to the well-known greedy approach to provide the
      objective measure of the sequential seeding benefits. Surprisingly, applying
      sequential seeding to a simple degree-based selection leads to higher coverage
      than achieved by the computationally expensive greedy approach currently
      considered to be the best heuristic.

PMID- 30228339
TI  - Single-electron charge sensing in self-assembled quantum dots.
AB  - Measuring single-electron charge is one of the most fundamental quantum
      technologies. Charge sensing, which is an ingredient for the measurement of
      single spins or single photons, has been already developed for semiconductor gate
      defined quantum dots, leading to intensive studies on the physics and the
      applications of single-electron charge, single-electron spin and photon-electron
      quantum interface. However, the technology has not yet been realized for self
      assembled quantum dots despite their fascinating transport phenomena and
      outstanding optical functionalities. In this paper, we report charge sensing
      experiments in self-assembled quantum dots. We choose two adjacent dots, and
      fabricate source and drain electrodes on each dot, in which either dot works as a
      charge sensor for the other target dot. The sensor dot current significantly
      changes when the number of electrons in the target dot changes by one,
      demonstrating single-electron charge sensing. We have also demonstrated real-time
      detection of single-electron tunnelling events. This charge sensing technique
      will be an important step towards combining efficient electrical readout of
      single-electron with intriguing quantum transport physics or advanced optical and
      photonic technologies developed for self-assembled quantum dots.

PMID- 30228342
TI  - Secrets of intercontinental flight.

PMID- 30228340
TI  - West Nile virus transmission and human infection risk in Veneto (Italy): a
      modelling analysis.
AB  - An intensified and continuous West Nile virus (WNV) spread across northern Italy
      has been observed since 2008, which caused more than one hundred reported human
      infections until 2016. Veneto is one of the Italian regions where WNV is
      considered endemic, and the greatest intensity of circulation was observed during
      2013 and 2016. By using entomological data collected across the region in those
      years, we calibrated a temperature-driven mathematical model through a Bayesian
      approach that simulates the WNV infection in an avian population with seasonal
      demography. We considered two alternative routes of life cycle re-activation of
      the virus at the beginning of each vector breeding season: in the first one the
      virus is maintained by infected birds, in the other by diapausing mosquitoes
      previously infected. Afterwards, we computed seasonal risk curves for human
      infection and quantified how they translate into reported symptomatic cases.
      According to our results, WNV is more likely to be re-activated each year via
      previously infected mosquitoes. The highest probability of human infection is
      expected to occur in August, consistently with observations. Our epidemiological
      estimates can be of particular interest for public health authorities, to support
      decisions in term of designing efficient surveillance plans and preventive
      measures.

PMID- 30228341
TI  - Subfossil trees suggest enhanced Mediterranean hydroclimate variability at the
      onset of the Younger Dryas.
AB  - Nearly 13,000 years ago, the warming trend into the Holocene was sharply
      interrupted by a reversal to near glacial conditions. Climatic causes and
      ecological consequences of the Younger Dryas (YD) have been extensively studied,
      however proxy archives from the Mediterranean basin capturing this period are
      scarce and do not provide annual resolution. Here, we report a hydroclimatic
      reconstruction from stable isotopes (delta18O, delta13C) in subfossil pines from
      southern France. Growing before and during the transition period into the YD (12
      900-12 600 cal BP), the trees provide an annually resolved, continuous sequence
      of atmospheric change. Isotopic signature of tree sourcewater (delta18Osw) and
      estimates of relative air humidity were reconstructed as a proxy for variations
      in air mass origin and precipitation regime. We find a distinct increase in inter
      annual variability of sourcewater isotopes (delta18Osw), with three major
      downturn phases of increasing magnitude beginning at 12 740 cal BP. The observed
      variation most likely results from an amplified intensity of North Atlantic (low
      delta18Osw) versus Mediterranean (high delta18Osw) precipitation. This marked
      pattern of climate variability is not seen in records from higher latitudes and
      is likely a consequence of atmospheric circulation oscillations at the margin of
      the southward moving polar front.

PMID- 30228343
TI  - Direct observation of dynamic interaction between a functional group in a single
      SBR chain and an inorganic matter surface.
AB  - As a composite of hybrid organic-inorganic materials, blending hydrophilic silica
      microparticles with oil-extended rubber can improve vehicle tire performance but
      the nanometer scale effects of microparticle inclusion have not been thoroughly
      studied. Here, we used atomic force microscopy (AFM) video imaging to closely
      investigate the behavior of functionalized and unmodified styrene-butadiene
      rubber (SBR), as models for tire rubber, on mica surfaces. The hydrophilic silica
      microparticle surface could be simulated by a mica substrate because both have
      silanol groups on their surface. Using AFM video imaging, we tracked the behavior
      of individual SBR polymer chains on mica surfaces to reveal how polymer
      modification affects the interaction of SBR with mica surfaces. We measured the
      diffusion coefficients and spring constants of single SBR polymer chains for the
      first time, demonstrating that it is possible to parameterize the relationship
      between the molecular dynamic structure of a polymer and rubber properties of the
      vulcanized compound.

PMID- 30228345
TI  - Reply to 'Sigmoidal Acquisition Curves are Good Indicators of Conformist
      Transmission'.
AB  - In the Smaldino et al. study 'Sigmoidal Acquisition Curves are Good Indicators of
      Conformist Transmission', our original findings regarding the conditional
      validity of using population-level sigmoidal acquisition curves as means to
      evidence individual-level conformity are contested. We acknowledge the
      identification of useful nuances, yet conclude that our original findings remain
      relevant for the study of conformist learning mechanisms.Replying to: Smaldino,
      P. E., Aplin, L. M. & Farine, D. R. Sigmoidal Acquisition Curves Are Good
      Indicators of Conformist Transmission. Sci. Rep. 8,
      https://doi.org/10.1038/s41598-018-30248-5 (2018).

PMID- 30228344
TI  - Effect of short-term high-temperature exposure on the life history parameters of
      Ophraella communa.
AB  - Extreme heat in summer is frequent in parts of China, and this likely affects the
      fitness of the beetle Ophraella communa, a biological control agent of invasive
      common ragweed. Here, we assessed the life history parameters of O. communa when
      its different developmental stages were exposed to high temperatures (40, 42 and
      44  degrees C, with 28  degrees C as a control) for 3 h each day for 3, 5, 5, and
      5 days, respectively (by stage). The larval stage was the most sensitive stage,
      with the lowest survival rate under heat stress. Egg and pupal survival
      significantly decreased only at 44  degrees C, and these two stages showed
      relative heat tolerance, while the adult stage was the most tolerant stage, with
      the highest survival rates. High temperatures showed positive effects on the
      female proportion, but there was no stage-specific response. Treated adults
      showed the highest fecundity under heat stress and a similar adult lifespan to
      that in the control. High temperatures decreased the F1 egg hatching rate, but
      the differences among stages were not significant. Negative carry-over effects of
      heat stress on subsequent stages and progenies' survival were also observed.
      Overall, heat effects depend on the temperature and life stage, and the adult
      stage was the most tolerant stage. Ophraella communa possesses a degree of heat
      tolerance that allows it to survive on hot days in summer.

PMID- 30228347
TI  - The (chain) terminators.

PMID- 30228346
TI  - Highly-sensitive optical organic vapor sensor through polymeric swelling induced
      variation of fluorescent intensity.
AB  - Traditional optical organic vapor sensors with solvatochromic shift mechanisms
      have lower sensitivity due to weak intermolecular interactions. Here, we report a
      general strategy to prepare a higher sensitivity optical organic vapor sensor
      through polymeric swelling-induced variation of fluorescent intensity. We combine
      one-dimensional polymeric structures and aggregation-induced emission (AIE)
      molecules together to form a polymer/AIE microwires array as a sensor. The
      prepared sensors based on different commercial polymers can successfully classify
      and identify various organic vapors. Among them, the poly(vinyl butyral)/AIE
      microwires array can detect methanol vapor as low as 0.05% of its saturation
      vapor pressure. According to the theory of like dissolves like, we further
      fabricate a polymer/AIE microwires array derived from designable
      polyethersulfones, through regulating their side chains, to distinguish similar
      organic vapors of benzene and toluene. Both experimental and theoretical
      simulation results reveal that specific molecular interactions between the
      polyethersulfones and organic vapors can improve the specific recognition
      performance of the sensors.

PMID- 30228348
TI  - Regulation of microRNA biogenesis and its crosstalk with other cellular pathways.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs that inhibit the expression of
      target genes by directly binding to their mRNAs. miRNAs are transcribed as
      precursor molecules, which are subsequently cleaved by the endoribonucleases
      Drosha and Dicer. Mature miRNAs are bound by a member of the Argonaute (AGO)
      protein family to form the RNA-induced silencing complex (RISC) in a process
      termed RISC loading. Advances in structural analyses of Drosha and Dicer
      complexes enabled elucidation of the mechanisms that drive these molecular
      machines. Transcription of miRNAs, their processing by Drosha and Dicer and RISC
      loading are key steps in miRNA biogenesis, and various additional factors
      facilitate, support or inhibit these processes. Recent work has revealed that
      regulatory factors not only coordinate individual miRNA processing steps but also
      connect miRNA biogenesis with other cellular processes. Protein phosphorylation,
      for example, links miRNA biogenesis to various signalling pathways, and such
      modifications are often associated with disease. Furthermore, not all miRNAs
      follow canonical processing routes, and many non-canonical miRNA biogenesis
      pathways have recently been characterized.

PMID- 30228349
TI  - Inositol polyphosphate 4-phosphatase type II regulation of androgen receptor
      activity.
AB  - Activation and transcriptional reprogramming of AR in advanced prostate cancer
      frequently coincides with the loss of two tumor suppressors, INPP4B and PTEN,
      which are highly expressed in human and mouse prostate epithelium. While
      regulation of AR signaling by PTEN has been described by multiple groups, it is
      not known whether the loss of INPP4B affects AR activity. Using prostate cancer
      cell lines, we showed that INPP4B regulates AR transcriptional activity and the
      oncogenic signaling pathways Akt and PKC. Analysis of gene expression in prostate
      cancer patient cohorts showed a positive correlation between INPP4B expression
      and both AR mRNA levels and AR transcriptional output. Using an Inpp4b-/- mouse
      model, we demonstrated that INPP4B suppresses Akt and PKC signaling pathways and
      modulates AR transcriptional activity in normal mouse prostate. Remarkably, PTEN
      protein levels and phosphorylation of S380 were the same in Inpp4b-/- and WT
      males, suggesting that the observed changes were due exclusively to the loss of
      INPP4B. Our data show that INPP4B modulates AR activity in normal prostate and
      its loss contributes to the AR-dependent transcriptional profile in prostate
      cancer.

PMID- 30228350
TI  - Flow-induced platelet activation in components of the extracorporeal membrane
      oxygenation circuit.
AB  - Extracorporeal membrane oxygenation (ECMO) is used for rescue in severe
      respiratory and/or circulatory failure. The patient's blood is pumped over
      artificial surfaces in the ECMO circuit. A platelet activation model was applied
      to study the potential thrombogenicity of ECMO circuit components: the
      centrifugal blood pump, cannulae, and tubing connectors. Based on the accumulated
      effect of the scalar form of the stress acting on the platelet over time, the
      activation model enables assessment of platelet activation and pinpoints regions
      of elevated activation risk in a component. Numerical simulations of the flow in
      different components of the ECMO circuit was carried out where the activation
      level is a function of the impact of local stress and its history along the path
      that the platelets follow. The results showed that the pump carried the largest
      risk for platelet activation followed by the reinfusion cannula and lastly the
      connectors. Pump thrombogenicity was mainly due to long residence time and high
      shear-rate while the connector showed a high level of non-stationary shear-rate
      that in turn may contribute to the formation of aggregates through direct
      platelet activation or through high shear-rate modulation of the vWF multimers.

PMID- 30228351
TI  - Sigmoidal Acquisition Curves Are Good Indicators of Conformist Transmission.
AB  - The potential for behaviours to spread via cultural transmission has profound
      implications for our understanding of social dynamics and evolution. Several
      studies have provided empirical evidence that local traditions can be maintained
      in animal populations via conformist learning (i.e. copying the majority). A
      conformist bias can be characterized by a sigmoidal relationship between a
      behavior's prevalence in the population and an individual's propensity to adopt
      that behavior. For this reason, the presence of conformist learning in a
      population is often inferred from a sigmoidal acquisition curve in which the
      overall rate of adoption for the behavior is taken as the dependent variable.
      However, the validity of sigmoidal acquisition curves as evidence for conformist
      learning has recently been challenged by models suggesting that such curves can
      arise via alternative learning rules that do not involve conformity. We review
      these models, and find that the proposed alternative learning mechanisms either
      rely on faulty or unrealistic assumptions, or apply only in very specific cases.
      We therefore recommend that sigmoidal acquisition curves continue to be taken as
      evidence for conformist learning. Our paper also highlights the importance of
      understanding the generative processes of a model, rather than only focusing
      solely on the patterns produced. By studying these processes, our analysis
      suggests that current practices by empiricists have provided robust evidence for
      conformist transmission in both humans and non-human animals.Arising from:
      Acerbi, A. et al. Sci. Rep. 6, 36068 (2016); https://doi.org/10.1038/srep36068 .

PMID- 30228353
TI  - Orbitropic Effect in Superfluid 3He B-phase Boundaries.
AB  - In this work, we study the influence of orbital viscosity on the evolution of the
      order-parameter and texture in the B phase of superfluid 3He near a moving
      boundary. From the redistribution of thermal quasiparticles within the texture,
      we develop a model which confers a substantial effective mass on the interface,
      and provides a new mechanism for friction as the boundary moves. We have tested
      the model against existing data for the motion of an A-B interface whose motion
      was controlled by a magnetic field. The model allows us to make predictions for
      the behaviour in experimental situations which involve texture rearrangement
      arising from motion of the B-phase boundary.

PMID- 30228352
TI  - Hemodialysis-related changes in phenotypical features of monocytes.
AB  - Hemodialysis (HD) patients exhibit chronic inflammation and leukocyte activation.
      We investigated the surface-marker profile of monocytes by flow cytometry to
      assess the chronic effect of uremia and the acute effect of dialysis on their
      phenotypical and functional features in 16 healthy controls (CON) and 15 HD
      patients before and after a polysulfone-based dialysis session. Median
      fluorescence intensities were analyzed indicating expression of CD14, CD16,
      integrins (CD11b, CD18), chemokine receptors (CCR2, CX3CR1), scavenger receptors
      (CD36, CD163) and Toll-like receptor-2 (TLR2). Before and after dialysis, HD
      patients harbour 0.9-fold less CD14++CD16- (Mo1), 1.8-fold more CD14++CD16+ (Mo2)
      and CD14+CD16++ (Mo3) monocytes than CON. HD patients' Mo1 showed elevated
      expression of CD11b (1.7-fold), CD18 (1.2-fold) and CD36 (2.1-fold), whereas
      CD163 expression was reduced in Mo1 and Mo2 (0.6-fold) compared to CON. These
      markers remained unaffected by dialysis. CX3CR1 expression on Mo2 and Mo3 was
      lower in HD patients before (0.8-fold) and further diminished after dialysis (0.6
      fold). Stimulation of monocytes resulted in diminished responses in HD patients
      compared to CON. In conclusion, a systematic analysis of the expression of
      particular surface markers on distinct monocyte subsets may help to distinguish
      between uremia and/or dialysis induced effects and to evaluate the functionality
      of monocytes and biocompatibility of HD.

PMID- 30228355
TI  - WFPHA: World federation of public health associations www.wfpha.org : Bettina
      Borisch and Marta Lomazzi, Federation's Pages Editors.

PMID- 30228354
TI  - Features and Associated Factors of the Behavioral Development of 24-month-old
      Children in Rural China: Follow-up Evaluation of a Randomized Controlled Trial.
AB  - The aim of this study was to assess the risk factors associated with the
      behavioral development among 24-month-old children in rural northwestern China. A
      total of 657 children whose mothers had participated in a double-blinded,
      randomized, controlled trial of antenatal micronutrient supplementation in
      western China were followed until 24 months of age. Their mental, psychomotor,
      and behavioral development were assessed by the Bayley Scales of Infant
      Development. Multivariate logistic regression models were used to examine the
      factors associated with infant behavioral development. Six behavioral factors of
      infants were presented: activity, social adaptability, reactivity, endurance,
      concentration, and motor coordination. Further analysis demonstrated that
      maternal malnutrition, exposure to risk factors during pregnancy, and adverse
      birth outcomes negatively affected the behavioral development of children at 24
      months, which is a common co-occurrence with cognitive and emotional problems.
      These results suggest that strategies to improve infant behavioral development
      should consider the maternal pregnancy status.

PMID- 30228356
TI  - Differential Proteome Analysis of Human Neuroblastoma Xenograft Primary Tumors
      and Matched Spontaneous Distant Metastases.
AB  - Metastasis formation is the major cause for cancer-related deaths and the
      underlying mechanisms remain poorly understood. In this study we describe
      spontaneous metastasis xenograft mouse models of human neuroblastoma used for
      unbiased identification of metastasis-related proteins by applying an infrared
      laser (IR) for sampling primary tumor and metastatic tissues, followed by mass
      spectrometric proteome analysis. IR aerosol samples were obtained from ovarian
      and liver metastases, which were indicated by bioluminescence imaging (BLI), and
      matched subcutaneous primary tumors. Corresponding histology proved the human
      origin of metastatic lesions. Ovarian metastases were commonly larger than liver
      metastases indicating differential outgrowth capacities. Among ~1,900 proteins
      identified at each of the three sites, 55 proteins were differentially regulated
      in ovarian metastases while 312 proteins were regulated in liver metastases.
      There was an overlap of 21 and 7 proteins up- and down-regulated at both
      metastatic sites, respectively, most of which were so far not related to
      metastasis such as LYPLA2, EIF4B, DPY30, LGALS7, PRPH, and NEFM. Moreover, we
      established in vitro sublines from primary tumor and metastases and demonstrate
      differences in cellular protrusions, migratory/invasive potential and
      glycosylation. Summarized, this work identified several novel putative drivers of
      metastasis formation that are tempting candidates for future functional studies.

PMID- 30228358
TI  - Coherence in defect evolution data for the ion beam irradiated graphene.
AB  - The defect evolution in graphene produced by ion beam bombardment is investigated
      by changing the ion species, irradiation energy and dose. Raman spectroscopy is
      performed to examine the defect yield produced under various ion beam bombardment
      conditions. The defect yields of the vacancy-type defect are well described by
      the linear energy transfer (L) and dose (d). By increasing Ld, the defect yields
      exhibit similar behaviours for all ion species. As a consequence, all the defect
      yields can be collapsed into a single curve by multiplying them by a single
      parameter, suggesting that the defect evolution under various ion beam
      bombardment conditions can be described in a simple formula.

PMID- 30228357
TI  - Variations of cingulate sulcal organization and link with cognitive performance.
AB  - The sulcal morphology of the human medial frontal cortex has received marked
      interest because of (1) its remarkable link with the functional organization of
      this region, and (2) observations that deviations from 'normal' sulcal
      morphological variability correlate with the prevalence of some psychiatric
      disorders, cognitive abilities, or personality traits. Unfortunately, background
      studies on environmental or genetic factors influencing the ontogenesis of the
      sulcal organization in this region are critically lacking. We analysed the sulcal
      morphological organization in this region in twins and non-twin siblings, as well
      as in control subjects for a total of 599 subjects from the Human Connectome
      Project. The data first confirm significant biases in the presence of
      paracingulate sulci in left vs right hemispheres in the whole population (twin: p
      < 2.4.10-9; non-twin: p < 2.10-6) demonstrating a clear general laterality in
      human subjects. Second, measures of similarity between siblings and estimations
      of heritability suggest significant environmental factors, in particular in-womb
      environment, and weak additive genetic factors influencing the presence of a
      paracingulate sulcus. Finally, we found that relationships between sulcal
      organization and performance in cognitive, motor, and affective tests depend on
      the twin status (Twins versus Non-twins). These results provide important new
      insights to the issue of the significance of sulcal organization in the human
      medial frontal cortex.

PMID- 30228359
TI  - Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336
      Antiviral to Inhibit Encephalitic Alphavirus Infection.
AB  - Venezuelan equine encephalitis virus (VEEV) poses a major public health risk due
      to its amenability for use as a bioterrorism agent and its severe health
      consequences in humans. ML336 is a recently developed chemical inhibitor of VEEV,
      shown to effectively reduce VEEV infection in vitro and in vivo. However, its
      limited solubility and stability could hinder its clinical translation. To
      overcome these limitations, lipid-coated mesoporous silica nanoparticles (LC
      MSNs) were employed. The large surface area of the MSN core promotes hydrophobic
      drug loading while the liposome coating retains the drug and enables enhanced
      circulation time and biocompatibility, providing an ideal ML336 delivery
      platform. LC-MSNs loaded 20 +/- 3.4 MUg ML336/mg LC-MSN and released 6.6 +/- 1.3
      MUg/mg ML336 over 24 hours. ML336-loaded LC-MSNs significantly inhibited VEEV in
      vitro in a dose-dependent manner as compared to unloaded LC-MSNs controls.
      Moreover, cell-based studies suggested that additional release of ML336 occurs
      after endocytosis. In vivo safety studies were conducted in mice, and LC-MSNs
      were not toxic when dosed at 0.11 g LC-MSNs/kg/day for four days. ML336-loaded LC
      MSNs showed significant reduction of brain viral titer in VEEV infected mice
      compared to PBS controls. Overall, these results highlight the utility of LC-MSNs
      as drug delivery vehicles to treat VEEV.

PMID- 30228360
TI  - Development of a novel UHPLC-MS/MS-based platform to quantify amines, amino acids
      and methylarginines for applications in human disease phenotyping.
AB  - Amine quantification is an important strategy in patient stratification and
      personalised medicine. This is because amines, including amino acids and
      methylarginines impact on many homeostatic processes. One important pathway
      regulated by amine levels is nitric oxide synthase (NOS). NOS is regulated by
      levels of (i) the substrate, arginine, (ii) amino acids which cycle with arginine
      and (iii) methylarginine inhibitors of NOS. However, biomarker research in this
      area is hindered by the lack of a unified analytical platform. Thus, the
      development of a common metabolomics platform, where a wide range of amino acids
      and methylarginines can be measured constitutes an important unmet need. Here we
      report a novel high-throughput ultra-high performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS) platform where ~40 amine analytes,
      including arginine and methylarginines can be detected and quantified on a molar
      basis, in a single sample of human plasma. To validate the platform and to
      generate biomarkers, human plasma from a well-defined cohort of patients before
      and after coronary artery bypass surgery, who developed systemic inflammatory
      response syndrome (SIRS), were analysed. Bypass surgery with SIRS significantly
      altered 26 amine analytes, including arginine and ADMA. Consequently, pathway
      analysis revealed significant changes in a range of pathways including those
      associated with NOS.

PMID- 30228361
TI  - Mucosal microbiota of intestinal polyps reveals putative biomarkers of colorectal
      cancer.
AB  - The human intestine retains a complex microbial ecosystem, which performs crucial
      functions that impact on host health. Several studies have indicated that
      intestinal dysbiosis may impact on the establishment of life-threatening
      intestinal diseases such as colorectal cancer. An adenomatous polyp is the result
      of abnormal tissue growth, which is benign but is considered to be associated
      with a high risk of developing colorectal cancer, based on its grade of
      dysplasia. Development of diagnostic tools that are based on surveying the gut
      microbiota and are aimed at early detection of colorectal cancer represent highly
      desirable target. For this purpose, we performed a pilot study in which we
      applied a metataxonomic analysis based on 16S rRNA gene sequencing approach to
      unveil the composition of microbial communities of intestinal polyps. Moreover,
      we performed a meta-analysis involving the reconstructed microbiota composition
      of adenomatous polyps and publicly available metagenomics datasets of colorectal
      cancer. These analyses allowed the identification of microbial taxa such as
      Faecalibacterium, Bacteroides and Romboutsia, which appear to be depleted in
      cancerogenic mucosa as well as in adenomatous polyps, thus representing novel
      microbial biomarkers associated with early tumor formation. Furthermore, an
      absolute quantification of Fusubacterium nucleatum in polyps further compounded
      the important role of this microorganism as a valuable putative microbial
      biomarker for early diagnosis of colorectal cancer.

PMID- 30228362
TI  - An effective and concise device for detecting cold allodynia in mice.
AB  - Detection of cold allodynia is a very important aspect in the study of pain
      behavior. An effective and concise device for detecting cold pain has always been
      the hope of many researchers. Here, an easily produced and operated cold plate
      device is presented for the assessment of cold allodynia in mice. The device used
      to detect cold allodynia has two components: a chamber consists of a cylinder for
      animal experiment and a cube box around the chamber for holding ice to keep
      temperature stable. In the testing chamber, a mouse was placed on the circular
      plexiglass plate steady at 4  degrees C above ice for five minutes. The tested
      mouse will lift its paw when exposed to the cold plate. The number of lifts will
      present animal's response to the degree of cold stimulation. To evaluate this
      approach, three commonly used pain models of mice were tested: formalin test,
      bone cancer pain (BCP), and chronic constriction injury (CCI). As is reported in
      other literatures, these three pain mice models showed increased sensitivity to
      cold stimulation. The new device is indeed suitable for detecting cold allodynia
      behavior in mice. Comparisons with existing devices of detecting cold allodynia,
      such as the cold plate in the market (UGO, Panlab, Columbus, etc.), the new
      device has the advantages of low cost, simple operation and easy popularization
      and can detect cold allodynia behavior of mice very well. This is a very
      practical and economical device to detect cold allodynia behavior.

PMID- 30228363
TI  - Analysis of Racial/Ethnic Representation in Select Basic and Applied Cancer
      Research Studies.
AB  - Over the past decades, consistent studies have shown that race/ethnicity have a
      great impact on cancer incidence, survival, drug response, molecular pathways and
      epigenetics. Despite the influence of race/ethnicity in cancer outcomes and its
      impact in health care quality, a comprehensive understanding of racial/ethnic
      inclusion in oncological research has never been addressed. We therefore explored
      the racial/ethnic composition of samples/individuals included in fundamental
      (patient-derived oncological models, biobanks and genomics) and applied cancer
      research studies (clinical trials). Regarding patient-derived oncological models
      (n = 794), 48.3% have no records on their donor's race/ethnicity, the rest were
      isolated from White (37.5%), Asian (10%), African American (3.8%) and Hispanic
      (0.4%) donors. Biobanks (n = 8,293) hold specimens from unknown (24.56%), White
      (59.03%), African American (11.05%), Asian (4.12%) and other individuals (1.24%).
      Genomic projects (n = 6,765,447) include samples from unknown (0.6%), White
      (91.1%), Asian (5.6%), African American (1.7%), Hispanic (0.5%) and other
      populations (0.5%). Concerning clinical trials (n = 89,212), no racial/ethnic
      registries were found in 66.95% of participants, and records were mainly obtained
      from Whites (25.94%), Asians (4.97%), African Americans (1.08%), Hispanics
      (0.16%) and other minorities (0.9%). Thus, two tendencies were observed across
      oncological studies: lack of racial/ethnic information and overrepresentation of
      Caucasian/White samples/individuals. These results clearly indicate a need to
      diversify oncological studies to other populations along with novel strategies to
      enhanced race/ethnicity data recording and reporting.

PMID- 30228365
TI  - A novel truncating mutation in MYH3 causes spondylocarpotarsal synostosis
      syndrome with basilar invagination.
AB  - Spondylocarpotarsal synostosis syndrome (SCT) is a rare group of skeletal
      dysplasias, characterized by disproportionate short stature with a short trunk,
      abnormal segmentation of the spine with vertebral fusion, scoliosis and lordosis,
      carpal and tarsal synostosis, and mild facial dysmorphisms. While the majority of
      the cases show autosomal recessive inheritance, only a few cases of vertical
      transmissions, with MYH3 mutations, have been reported. Here we report a case
      with typical SCT, carrying a novel heterozygous mutation in MYH3. This
      observation supports the hypothesis of a pathogenic link between autosomal
      dominant SCT and heterozygous mutations in MYH3. Of note, our case showed basilar
      invagination on brain magnetic resonance imaging at the age of 10 years. Basilar
      invagination could be a rare complication of both autosomal recessive and
      dominant SCT, indicating that prompt investigation are warranted for SCT
      patients.

PMID- 30228364
TI  - Molecular pathogenesis of triple-negative breast cancer based on microRNA
      expression signatures: antitumor miR-204-5p targets AP1S3.
AB  - Triple-negative breast cancer (TNBC) is an aggressive type of cancer associated
      with a poor prognosis. Identification of novel therapeutic targets in TNBC is
      urgently needed. Here, we investigated the microRNA (miRNA) expression signature
      of TNBC using clinical specimens. In total, 104 miRNAs (56 upregulated and 48
      downregulated) were significantly dysregulated in TNBC tissues; miR-204-5p showed
      the most dramatic downregulation. We then examined the antitumor roles of miR-204
      5p in breast cancer (BC) cells. Notably, cancer cell migration and invasion were
      significantly reduced by ectopic expression of miR-204-5p in BC cells. Genome
      wide gene expression analysis and in silico database search revealed that 32
      genes were putative miR-204-5p targets. High expression of AP1S3, RACGAP1,
      ELOVL6, and LRRC59 was significantly associated with poor prognosis in patients
      with BC, and adaptor-related protein complex 1 sigma 3 subunit (AP1S3) was
      directly regulated by miR-204-5p, as demonstrated by luciferase reporter assays.
      AP1S3 overexpression was detected in TNBC clinical specimens and enhanced cancer
      cell aggressiveness. We further analyzed downstream RNA networks regulated by
      AP1S3 in BC cells. Overall, this miRNA signature is expected to be an effective
      tool for identification of miRNA-mediated molecular mechanisms of TNBC
      pathogenesis.

PMID- 30228367
TI  - Post-streptococcal uveitis syndrome in a Caucasian population: a case series.
AB  - BACKGROUND/OBJECTIVES: Uveitis is an uncommon manifestation of post-streptococcal
      syndrome (PSUS). Despite reports, the condition is often not well recognised. The
      purpose of this study is to report a case series of children with post
      streptococcal uveitis. SUBJECTS/METHODS: In this retrospective case series, all
      cases of PSUS were identified from all new paediatric patients diagnosed with
      uveitis over a 6-year period. Diagnosis of PSUS was based on the following
      diagnostic criteria: unilateral or bilateral uveitis with positive anti
      streptolysin O titres (ASOT) or anti-deoxyribonuclease (anti-DNase) titres, and
      negative routine investigations for other causes of uveitis. RESULTS: Eleven
      Caucasian paediatric patients were diagnosed with PSUS. One had a novel finding
      of peripheral corneal endotheliopathy, 73% of patients presented in spring or
      winter months and 88% of eyes had a final VA of better than or equal to 6/12 at a
      mean follow-up of 22 months. Systemic immunosuppressant treatment was used in 36%
      of patients. Adalimumab was used in 18% of patient's refractory to other
      treatment. CONCLUSIONS: We report on the largest consecutive series of Caucasian
      patients under 16 years of age with PSUS. We have demonstrated a seasonal
      preponderance with presentation typically in winter or spring. We report a novel
      finding of corneal endotheliopathy in one of our PSUS patients. We also report on
      the benefit of adalimumab in the management of severe cases of PSUS; use of
      biologics in this particular cohort of uveitis patients has not previously been
      reported. With aggressive treatment our patients achieved good visual outcomes
      comparable to other published series.

PMID- 30228366
TI  - Low-Frequency Oscillatory Correlates of Auditory Predictive Processing in
      Cortical-Subcortical Networks: A MEG-Study.
AB  - Emerging evidence supports the role of neural oscillations as a mechanism for
      predictive information processing across large-scale networks. However, the
      oscillatory signatures underlying auditory mismatch detection and information
      flow between brain regions remain unclear. To address this issue, we examined the
      contribution of oscillatory activity at theta/alpha-bands (4-8/8-13 Hz) and
      assessed directed connectivity in magnetoencephalographic data while 17 human
      participants were presented with sound sequences containing predictable
      repetitions and order manipulations that elicited prediction-error responses. We
      characterized the spectro-temporal properties of neural generators using a
      minimum-norm approach and assessed directed connectivity using Granger Causality
      analysis. Mismatching sequences elicited increased theta power and phase-locking
      in auditory, hippocampal and prefrontal cortices, suggesting that theta-band
      oscillations underlie prediction-error generation in cortical-subcortical
      networks. Furthermore, enhanced feedforward theta/alpha-band connectivity was
      observed in auditory-prefrontal networks during mismatching sequences, while
      increased feedback connectivity in the alpha-band was observed between
      hippocampus and auditory regions during predictable sounds. Our findings
      highlight the involvement of hippocampal theta/alpha-band oscillations towards
      auditory prediction-error generation and suggest a spectral dissociation between
      inter-areal feedforward vs. feedback signalling, thus providing novel insights
      into the oscillatory mechanisms underlying auditory predictive processing.

PMID- 30228368
TI  - Randomised, masked study of local anaesthesia administered prior to external
      dacryocystorhinostomy under general anaesthesia.
AB  - OBJECTIVES: To determine whether administration of local anaesthetic at the site
      of skin incision during open lacrimal drainage surgery under general anaesthesia
      alters the total dosage of anaesthetic drugs required during total intravenous
      anaesthesia (TIVA), and whether it alters postoperative pain and recovery. STUDY
      DESIGN: Masked comparison of a randomized, two-group interventional study.
      PATIENTS AND METHODS: Patients undergoing unilateral external
      dacryocystorhinostomy under total intravenous general anaesthesia were recruited
      from the lacrimal service at Moorfields Eye Hospital between September 2012 and
      February 2014. The patients were randomised to receive, after induction and
      stabilisation of general anaesthesia, infiltration of the ipsilateral paranasal
      tissues with 2.5 ml of 0.5% bupivacaine with 1:100000 epinephrine ("treatment"
      group), or a sham injection ("control" group); the infiltration was performed
      about 7 min prior to the skin incision. The infusion rates for propofol and
      remifentanil were adjusted to maintain a steady intra-operative mean blood
      pressure of 55-70 mmHg and BIS score of 40-60%. The time taken for extubation of
      the patient after cessation of TIVA was recorded, and postoperative pain scores
      (on a Likert scale from 0-10) were taken at regular intervals after extubation.
      The average intra-operative mean blood pressures, total drug usage, extubation
      time and pain scores for each of the two groups were compared using two-tail
      Student's t-testing and Wilcoxon rank sum testing. RESULTS: There were 12
      patients (7 female; 58%) in the treatment group and 11 (7 female; 64%) in the
      control group, with similar average age at surgery (59 years treatment, 53 years
      control; p = 0.38) The average operative time was 45 min in the treatment group
      (median 42, range 30-55) and 47 min (median 45; range 37-61) in the control group
      (p = 0.52). The mean dosage of propofol required to maintain satisfactory GA was
      significantly less in the "treatment" group (89.8 mcg/kg/min) as compared to the
      "control" group (mean 126 mcg/kg/min) (p = 0.0007). Likewise, remifentanil dosage
      was significantly less in the "treatment" group (100 ng/kg/min) as compared to
      controls (259 ng/kg/min) (p = 0.00007). The mean non-invasive blood pressure was
      consistently lower during surgery in the "treated" group, and showed less intra
      operative variation. After surgery, the patients receiving LA had a significantly
      shorter extubation time (mean time 6.0 min in "treated" group, 12.1 min in
      "controls"; P < 0.0002) and also significantly lower pain scores at 10, 30, 60,
      120 and 180 min after extubation (p < 0.01, p < 0.01, p < 0.01, p < 0.01 and p <
      0.05, respectively). CONCLUSIONS: Ipsilateral infiltration of local anaesthesia
      containing epinephrine in the paranasal tissues just prior to open
      dacryocystorhinostomy under total intravenous anaesthesia is associated with a
      28% reduction in mean propofol usage, and a 61% reduction in remifentanil usage.
      LA usage during GA also produces improved and less variable intra-operative mean
      blood pressures, a significantly shorter extubation time and significantly lower
      postoperative pain scores.

PMID- 30228371
TI  - Altered in utero kidney development in newborns with congenital heart disease.
AB  - BACKGROUND: It is known that the heart is not the only organ affected in
      congenital heart disease (CHD); there is growth restriction of both the brain and
      the whole body. The protective mechanism of "the brain-sparing phenomenon" re
      directs blood flow toward the growing brain in fetuses with CHD. We hypothesized
      that these changes would result in impaired fetal kidney growth. METHODS: The
      preoperative ultrasound measurements of kidney length were obtained
      retrospectively from 452 neonates requiring surgery for CHD. Percentiles were
      generated based on regression analysis of normative kidney length from three
      datasets according to both corrected gestational age and to birthweight. RESULTS:
      As a cohort, neonates with CHD have significantly enlarged kidneys, with a mean
      percentile ranging from 54.1-72.7 (p < 0.001), depending on the three normal
      population datasets used for comparison. The kidneys of neonates with left heart
      obstruction were consistently demonstrated to be greater than normal, unlike
      those with cyanotic heart disease which were shown to have either normal or
      enlarged kidneys, depending on the reference population used. CONCLUSIONS: The
      kidneys of newborns with CHD are not reduced in size, and on average are larger
      than normal. The nature of this size discrepancy and its subsequent clinical
      significance is unknown.

PMID- 30228370
TI  - Adjusting risk-taking to the annual cycle of long-distance migratory birds.
AB  - Life-history theory predicts that current behaviour affects future reproduction,
      implying that animals should optimise their escape strategies to reflect fitness
      costs and benefits of premature escape. Both costs and benefits of escape may
      change temporally with important consequences for the evolution of escape
      strategies. Moreover, escape strategies of species may differ according to their
      positions on slow-fast pace of life gradients. We studied risk-taking in long
      distance migratory animals, waders (Charadriiformes), during the annual cycle,
      i.e., breeding in Europe, stopover in the Middle East and wintering in tropical
      Africa. Phylogenetically informed comparative analyses revealed that risk-taking
      (measured as flight initiation distance, FID) changed significantly over the
      year, being lowest during breeding and peaking at stopover sites. Similarly,
      relationships between risk-taking and life-history traits changed among stages of
      the annual cycle. While risk-taking significantly decreased with increasing body
      mass during breeding, risk-taking-body mass relationship became marginally
      significant in winter and disappeared during migration. The positive trend of
      risk-taking along slow-fast pace of life gradient measured as adult survival was
      only found during breeding. The season-dependent relationships between risk
      taking and life history traits suggest that migrating animals respond to
      fluctuating environments by adopting behavioural plasticity.

PMID- 30228369
TI  - Increasing Acyl CoA thioesterase activity alters phospholipid profile without
      effect on insulin action in skeletal muscle of rats.
AB  - Increased lipid metabolism in muscle is associated with insulin resistance and
      therefore, many strategies have been employed to alter fatty acid metabolism and
      study the impact on insulin action. Metabolism of fatty acid requires activation
      to fatty acyl CoA by Acyl CoA synthases (ACSL) and fatty acyl CoA can be
      hydrolysed by Acyl CoA thioesterases (Acot). Thioesterase activity is low in
      muscle, so we overexpressed Acot7 in muscle of chow and high-fat diet (HFD) rats
      and investigated effects on insulin action. Acot7 overexpression modified
      specific phosphatidylcholine and phosphatidylethanolamine species in tibialis
      muscle of chow rats to levels similar to those observed in control HFD muscle.
      The changes in phospholipid species did not alter glucose uptake in tibialis
      muscle under hyperinsulinaemic/euglycaemic clamped conditions. Acot7
      overexpression in white extensor digitorum longus (EDL) muscle increased complete
      fatty acid oxidation ex-vivo but was not associated with any changes in glucose
      uptake in-vivo, however overexpression of Acot7 in red EDL reduced insulin
      stimulated glucose uptake in-vivo which correlated with increased incomplete
      fatty acid oxidation ex-vivo. In summary, although overexpression of Acot7 in
      muscle altered some aspects of lipid profile and metabolism in muscle, this had
      no major effect on insulin-stimulated glucose uptake.

PMID- 30228372
TI  - The clinical importance of a cytokine network in the acute phase of sepsis.
AB  - Sepsis remains a major cause of death. Cytokines interact closely with each other
      and play a crucial role in the progression of sepsis. We focussed on the
      associations of a cytokine network with prognosis and disease severities in
      sepsis. This retrospective study included 31 patients with sepsis and 13 healthy
      controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11
      and 15 and from healthy controls. Levels of PAI-1, IFN-alpha, IFN-gamma, IL
      1beta, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-alpha, MCP-1, IL-4 and IL-10 were
      measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times
      blood samples were taken. Network analysis revealed a network formed by PAI-1, IL
      6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis.
      There were positive correlations of each cytokine and the combined score (IL-6 +
      IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the
      acute phase. A Cox proportional hazards model focussed on the acute phase showed
      that the above combined score was significantly related with patient prognosis,
      suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a
      pivotal role in the acute phase of sepsis.

PMID- 30228373
TI  - Dynamic network targeting for closed-loop deep brain stimulation.

PMID- 30228374
TI  - Improved high temperature radiation damage tolerance in a three-phase ceramic
      with heterointerfaces.
AB  - Radiation damage tolerance for a variety of ceramics at high temperatures depends
      on the material's resistance to nucleation and growth of extended defects. Such
      processes are prevalent in ceramics employed for space, nuclear fission/fusion
      and nuclear waste environments. This report shows that random heterointerfaces in
      materials with sub-micron grains can act as highly efficient sinks for point
      defects compared to grain boundaries in single-phase materials. The concentration
      of dislocation loops in a radiation damage-prone phase (Al2O3) is significantly
      reduced when Al2O3 is a component of a composite system as opposed to a single
      phase system. These results present a novel method for designing exceptionally
      radiation damage tolerant ceramics at high temperatures with a stable grain size,
      without requiring extensive interfacial engineering or production of
      nanocrystalline materials.

PMID- 30228376
TI  - Selective phenol recovery via simultaneous hydrogenation/dealkylation of
      isopropyl- and isopropenyl-phenols employing an H2 generator combined with tandem
      micro-reactor GC/MS.
AB  - The pyrolysis of bisphenol A (BPA), an essential process ingredient used in
      industry and many everyday life products, helps produce low-industrial-demand
      chemicals such as isopropenyl- and isopropyl-phenols (IPP and iPrP). In this
      study, tandem micro-reactor gas chromatography/mass spectrometry combined with an
      H2 generator (H2-TR-GC/MS) was employed for the first time to investigate the
      selective recovery of phenol via simultaneous hydrogenation/dealkylation of IPP
      and iPrP. After investigating the iPrP dealkylation performances of several
      zeolites, we obtained full iPrP conversion with over 99% phenol selectivity using
      the Y-zeolite at 350  degrees C. In contrast, when applied to IPP, the zeolite
      acid centres caused IPP polymerisation and subsequent IPP-polymer cracking,
      resulting in many byproducts and reduced phenol selectivity. This challenge was
      overcome by the addition of 0.3 wt% Ni on the Y-zeolite (0.3Ni/Y), which enabled
      the hydrogenation of IPP into iPrP and subsequent dealkylation into phenol (full
      IPP conversion with 92% phenol selectivity). Moreover, the catalyst deactivation
      and product distribution over repetitive catalytic use were successfully
      monitored using the H2-TR-GC/MS system. We believe that the findings presented
      herein could allow the recovery of phenol-rich products from polymeric waste with
      BPA macro skeleton.

PMID- 30228378
TI  - Cardioimmunology: the immune system in cardiac homeostasis and disease.
AB  - The past few decades have generated growing recognition that the immune system
      makes an important contribution to cardiac development, composition and function.
      Immune cells infiltrate the heart at gestation and remain in the myocardium,
      where they participate in essential housekeeping functions throughout life. After
      myocardial infarction or in response to infection, large numbers of immune cells
      are recruited to the heart to remove dying tissue, scavenge pathogens and promote
      healing. Under some circumstances, immune cells can cause irreversible damage,
      contributing to heart failure. This Review focuses on the role of the immune
      system in the heart under both homeostatic and perturbed conditions.

PMID- 30228375
TI  - Sharing of human milk oligosaccharides degradants within bifidobacterial
      communities in faecal cultures supplemented with Bifidobacterium bifidum.
AB  - Gut microbiota of breast-fed infants are generally rich in bifidobacteria. Recent
      studies show that infant gut-associated bifidobacteria can assimilate human milk
      oligosaccharides (HMOs) specifically among the gut microbes. Nonetheless, little
      is known about how bifidobacterial-rich communities are shaped in the gut.
      Interestingly, HMOs assimilation ability is not related to the dominance of each
      species. Bifidobacterium longum susbp. longum and Bifidobacterium breve are
      commonly found as the dominant species in infant stools; however, they show
      limited HMOs assimilation ability in vitro. In contrast, avid in vitro HMOs
      consumers, Bifidobacterium bifidum and Bifidobacterium longum subsp. infantis,
      are less abundant in infant stools. In this study, we observed altruistic
      behaviour by B. bifidum when incubated in HMOs-containing faecal cultures. Four
      B. bifidum strains, all of which contained complete sets of HMO-degrading genes,
      commonly left HMOs degradants unconsumed during in vitro growth. These strains
      stimulated the growth of other Bifidobacterium species when added to faecal
      cultures supplemented with HMOs, thereby increasing the prevalence of
      bifidobacteria in faecal communities. Enhanced HMOs consumption by B. bifidum
      supplemented cultures was also observed. We also determined the complete genome
      sequences of B. bifidum strains JCM7004 and TMC3115. Our results suggest B.
      bifidum-mediated cross-feeding of HMOs degradants within bifidobacterial
      communities.

PMID- 30228379
TI  - Bacterial community structure in a sympagic habitat expanding with global
      warming: brackish ice brine at 85-90  degrees N.
AB  - Larger volumes of sea ice have been thawing in the Central Arctic Ocean (CAO)
      during the last decades than during the past 800,000 years. Brackish brine (fed
      by meltwater inside the ice) is an expanding sympagic habitat in summer all over
      the CAO. We report for the first time the structure of bacterial communities in
      this brine. They are composed of psychrophilic extremophiles, many of them
      related to phylotypes known from Arctic and Antarctic regions. Community
      structure displayed strong habitat segregation between brackish ice brine (IB;
      salinity 2.4-9.6) and immediate sub-ice seawater (SW; salinity 33.3-34.9),
      expressed at all taxonomic levels (class to genus), by dominant phylotypes as
      well as by the rare biosphere, and with specialists dominating IB and generalists
      SW. The dominant phylotypes in IB were related to Candidatus Aquiluna and
      Flavobacterium, those in SW to Balneatrix and ZD0405, and those shared between
      the habitats to Halomonas, Polaribacter and Shewanella. A meta-analysis for the
      oligotrophic CAO showed a pattern with Flavobacteriia dominating in melt ponds,
      Flavobacteriia and Gammaproteobacteria in solid ice cores, Flavobacteriia, Gamma-
      and Betaproteobacteria, and Actinobacteria in brine, and Alphaproteobacteria in
      SW. Based on our results, we expect that the roles of Actinobacteria and
      Betaproteobacteria in the CAO will increase with global warming owing to the
      increased production of meltwater in summer. IB contained three times more
      phylotypes than SW and may act as an insurance reservoir for bacterial diversity
      that can act as a recruitment base when environmental conditions change.

PMID- 30228377
TI  - Comparison of initial oral microbiomes of young adults with and without cavitated
      dentin caries lesions using an in situ biofilm model.
AB  - Dental caries is caused by acids released from bacterial biofilms. However, the
      in vivo formation of initial biofilms in relation to caries remains largely
      unexplored. The aim of this study was to compare the oral microbiome during the
      initial phase of bacterial colonization for individuals with (CC) and without
      (NC) cavitated dentin caries lesions. Bovine enamel slabs on acrylic splints were
      worn by the volunteers (CC: 14, NC: 13) for in situ biofilm formation (2 h, 4 h,
      8 h, 1 ml saliva as reference). Sequencing of the V1/V2 regions of the 16S rRNA
      gene was performed (MiSeq). The relative abundances of individual operational
      taxonomic units (OTUs) were compared between samples from the CC group and the NC
      group. Random forests models were furthermore trained to separate the groups.
      While the overall heterogeneity did not differ substantially between CC and NC
      individuals, several individual OTUs were found to have significantly different
      relative abundances. For the 8 h samples, most of the significant OTUs showed
      higher relative abundances in the CC group, while the majority of significant
      OTUs in the saliva samples were more abundant in the NC group. Furthermore, using
      OTU signatures enabled a separation between both groups, with area-under-the
      curve (AUC) values of ~0.8. In summary, the results suggest that initial oral
      biofilms provide the potential to differentiate between CC and NC individuals.

PMID- 30228380
TI  - Single-cell genomics uncover Pelagibacter as the putative host of the extremely
      abundant uncultured 37-F6 viral population in the ocean.
AB  - The identification of relevant virus-host pairs that globally account for a large
      pool of carbon and nutrients in the ocean is paramount to build accurate
      ecological models. A previous work using single-virus genomics led to the
      discovery of the uncultured single-virus vSAG 37-F6, originally sorted from the
      Mediterranean Sea (Blanes Bay Microbial Observatory), that represents one of the
      most abundant dsDNA viral population in the marine surface virosphere. Here, from
      same sampling site, we report that a Pelagibacter single-cell contained a viral
      member of vSAG 37-F6 population, by means of PCR screening of sorted, genome
      amplified single cells with vSAG 37-F6-specific primers and whole-genome
      sequencing. Furthermore, viruses from this population were also found in three
      other Pelagibacter single cells from the South Pacific and Atlantic oceans. These
      new uncultured pelagiphages were genetically different from the previously
      characterized pelagiphage isolates. Data showed that the uncultured vSAG 37-F6
      population represents the Pelagibacter phages that inhabit the sunlit ocean
      better, and contains a vast unrecognized microdiversity.

PMID- 30228381
TI  - Cross-exchange of B-vitamins underpins a mutualistic interaction between
      Ostreococcus tauri and Dinoroseobacter shibae.
AB  - Ostreococcus tauri, a picoeukaryotic alga that contributes significantly to
      primary production in oligotrophic waters, has a highly streamlined genome,
      lacking the genetic capacity to grow without the vitamins thiamine (B1) and
      cobalamin (B12). Here we demonstrate that the B12 and B1 auxotrophy of O. tauri
      can be alleviated by co-culturing with a heterotrophic bacterial partner
      Dinoroseobacter shibae, a member of the Rhodobacteraceae family of alpha
      proteobacteria, genera of which are frequently found associated with marine
      algae. D. shibae lacks the complete pathway to synthesise three other B-vitamins:
      niacin (B3), biotin (B7), and p-aminobenzoic acid (a precursor for folate, B9),
      and the alga is in turn able to satisfy the reciprocal vitamin requirements of
      its bacterial partner in a stable long-term co-culture. Bioinformatics searches
      of 197 representative marine bacteria with sequenced genomes identified just nine
      species that had a similar combination of traits (ability to make vitamin B12,
      but missing one or more genes for niacin and biotin biosynthesis enzymes), all of
      which were from the Rhodobacteraceae. Further analysis of 70 species from this
      family revealed the majority encoded the B12 pathway, but only half were able to
      make niacin, and fewer than 13% biotin. These characteristics may have either
      contributed to or resulted from the tendency of members of this lineage to adopt
      lifestyles in close association with algae. This study provides a nuanced view of
      bacterial-phytoplankton interactions, emphasising the complexity of the sources,
      sinks and dynamic cycling between marine microbes of these important organic
      micronutrients.

PMID- 30228382
TI  - Environmental non-persistent endocrine-disrupting chemicals exposure and
      reproductive hormones levels in adult men.
AB  - Non-persistent endocrine-disrupting chemicals (EDCs) are exogenous, man-made
      substances present in the environment that may interfere with the natural human
      hormones and may exert adverse consequences on human organism.
      Endocrinedisrupting chemicals have been suspected to be associated with altered
      reproductive function in the case of males and females. Environmental endocrine
      disrupting non-persistent chemicals like parabens, phthalates, bisphenol A (BPA),
      synthetic pyrethroids and organophosphate pesticides are found in various
      products such as metal food cans, plastic bottles, detergents, personal care
      products or chemicals used for fighting against insects. The widespread
      distribution of these chemicals causes that humans are permanently exposed
      through multiple sources. The aim of this review is to summarize data linking non
      persistent endocrine-disrupting chemicals exposure, and human, male reproductive
      hormones levels. The included studies were selected by searched PubMed, Web of
      Science and MEDLINE, original papers published from 2006 to 2016 and referring to
      human data were included to the review. The results of reviewed studies were not
      consistent, however, majority of the studies indicated that non-persistent EDCs
      may affect male reproductive hormones levels. Most findings suggest that exposure
      to environmental EDCs is negatively related to the level of testosterone (except
      for exposure to BPA which is positively associated). In most of the studies
      negative association was found between exposure to examined EDCs and free
      androgen index, too. Considering the suggested health effect of exposure to EDCs,
      more epidemiological data is needed. Int J Occup Med Environ Health
      2018;31(5):551-573.

PMID- 30228384
TI  - Honey moisture reduction and its quality.
AB  - Beekeeping has been widely promoted in many countries as a major contributor to
      rural development. Honey is a sweet and viscous liquid which has sweetness due to
      the presence of monosaccharides. The major constituents of honey are sugars,
      water, proteins, enzymes, acids and minerals, while the major causes of quality
      deterioration include heating at high temperatures, high moisture content,
      adulteration, poor packaging and poor storage conditions. Heating not only eases
      the processing of bottling by reducing the viscosity of honey, but also reduces
      the water content in honey to prevent fermentation and delays the granulation by
      destroying large sugar nuclei. The paper discusses about the different honey
      moisture reduction systems designed by research workers as well as beekeepers at
      farm level and the different quality parameters affected by thermal treatment of
      honey.

PMID- 30228383
TI  - Nanoencapsulation of carotenoids: a focus on different delivery systems and
      evaluation parameters.
AB  - Different types of nanoparticles have been synthesized to protect carotenoids
      against exposition of external factors such as light, heat and oxygen; and
      processing conditions; to increase stability and to improve the bioavailability
      of nanoencapsulated carotenoid. The type of nanostructure synthesized
      (nanoemulsions, liposomes, solid lipid nanoparticles, nanostructured lipid
      carrier, and polymeric nanoparticles) influences on the synthesis and
      nanoparticles stability, which reflect in physic-chemical characteristics such as
      polydispersity index, zeta potential, and encapsulation efficiency. Different
      nanostructures can be used to improve stability of carotenoids; however,
      currently, polymeric nanocapsules are the nanostructure most utilized due to its
      stability during storage, high efficiency to encapsulate and to control the
      release of the carotenoid encapsulated. Due to these considerations, they have
      been focus of researchers for future studies regarding to application of
      carotenoids nanoencapsulated by food industries. The focus of this review is the
      presentation of different carotenoids delivery systems and the use of techniques
      to evaluate parameters that might limit the application of this innovative and
      potential technology in cosmetic, pharmaceutical and food industry.

PMID- 30228385
TI  - Effect of various food processing and handling methods on preservation of natural
      antioxidants in fruits and vegetables.
AB  - Bioactive compounds from plant sources are generally categorized as natural
      antioxidants with well-known health benefits. The health-promoting
      characteristics of natural antioxidants include anti-inflammatory, anti-diabetic,
      and hepatic effects as well as free radical scavenging. Herein, a comprehensive
      and comparative review are presented about the effects of conventional (thermal
      and mechanical) and relatively new (non-thermal) processing methods on
      phytochemicals and discussed the importance of implementing the use of those
      methods that could be of very helpful retaining the quality of the bioactive
      compounds in plant-based foods. Plant-based foods rich in phenolics, vitamin C,
      carotenoids, and other compounds undergo a range of processing operations before
      they are consumed. Most of these methods involve thermal treatments of fruits,
      stems, leaves, and roots. These techniques have varying effects on bioactive
      compounds and their activities, and the magnitude of these effects depends on
      process parameters such as temperature, time, and the food matrix. Thermal
      processing can be detrimental to bioactive compounds while nonthermal procedures
      may not cause significant deterioration of important health-promoting
      phytochemicals and in some cases can improve their bio-activity and bio
      availability. The detrimental effects of conventional processing on the quality
      of natural antioxidants have been compared to the effects of innovative
      nonthermal food treatments such as gamma and ultraviolet irradiation, ultraviolet
      light, pulsed electric fields, and high hydrostatic pressure.

PMID- 30228387
TI  - Functional properties of flours and protein concentrates of 3 strains of the
      edible mushroom Pleurotus ostreatus.
AB  - Pleurotus ostreatus is an edible mushroom with significant nutritional properties
      and highly valuable protein concentrates can be obtained from its fruit bodies.
      Functional properties of flours and protein concentrates derived from 3 Pleurotus
      ostreatus strains (PCM, POS and hybrid PCM * POS) were evaluated in this
      investigation. Fruit bodies were produced on wheat straw substrate, flours were
      obtained from dried and grinded fruit bodies and protein concentrates were
      extracted from flours by alkaline solubilization. For all 3 strains, pale yellow
      flours were obtained and protein concentrates showed a grayish brown color. Flour
      bulk densities ranged from 0.52 to 0.64 g/mL, a higher value than those for
      protein concentrates, i.e. 0.30-0.35 g/mL. The highest water absorption
      capacities (WAC) were observed for flours (300-418.8%) while protein concentrates
      presented higher oil absorption capacity (OAC) (173.3-214.1%). Flours and protein
      concentrates presented a minimal gelation concentration of 2%. Protein
      concentrates showed a higher foam capacity formation (FC) at pH 8. Likewise,
      flours and protein concentrates presented higher foam stability (FS) at alkaline
      pH (8 and 10). Emulsion activity index (EAI) for flours ranged from 3.96 to 26.68
      m2 g-1 whereas for protein concentrates ranged from 1.55 to 10.28 m2 g-1. These
      results indicate that flours and protein concentrates from P. ostreatus have
      remarkable functional properties, valuable in food industry where foaming and
      emulsifying properties are required.

PMID- 30228386
TI  - Chemical characterization of wash water biomass from shrimp surimi processing and
      its application to develop functional edible films.
AB  - The aim of this work was to recover and study the composition of the biomass
      obtained from the surimi processing industry, and to explore the feasibility of
      its valorization by developing functional edible films. A concentrate from wash
      water of minced shrimp muscle of low commercial value [shrimp concentrate (SC)]
      was obtained by alkaline solubilization and isoelectric precipitation, which had
      protein content of 61.8% and fat 23.6%. The protein fraction of low molecular
      weight (<=37 kDa), with maximum solubility at basic pH 9-11, and was rich in
      essential amino acids (296 essential amino acids/1000 residues), whereas the fat
      fraction showed a high degree of unsaturation (26.8% MUFA, 28.3% PUFA). SC,
      showed antioxidant activity measured by FRAP and ABTS assays and, was
      successfully incorporated into an agar film matrix (agar-to-protein ratio of
      3:1). The films were translucent and brownish and maintained integrity upon
      immersion in water, but swelled considerably. Films were able to release protein
      and exert antioxidant activity in water and 95% ethanol (aqueous and fatty food
      simulants, respectively), the release being faster and greater in the former. In
      conclusion, the biomass obtained from shrimp mince/surimi processing was for
      developing edible films.

PMID- 30228388
TI  - Evaluation of capsaicinoid profile and antioxidant properties in dried Korean red
      pepper (Capsicum annuum L.) as affected by variable dose rates of electron beam
      and gamma ray irradiation.
AB  - The application of food irradiation is based on the parameters including energy
      (MeV), dose rate (kGy/s or kGy/h), and absorbed dose (kGy). Red pepper powders
      were treated with different dose rates of 1, and 5 kGy/s electron beam (EB) as
      well as 1.8 and 9 kGy/h gamma ray (GR) in separate experiments. Constant absorbed
      dose (3 kGy) was maintained to observe whether different dose rates affect the
      product quality. Total and individual capsaicinoids increased at low EB and GR
      dose rates. Vitamin C content decreased at all dose rates, except at low GR dose
      rate, where no significant difference was observed. Low EB dose rate led to a
      marked increase (21%) in the total phenolics than high dose rate (13%). In
      contrast, high GR dose rate increased the total phenolics than low dose rate.
      Maximum antioxidants (1.36 mg TE/mL) were observed at high EB dose rate, although
      low dose rate also increased the antioxidant activity. Results indicated that
      different dose rates delivering the same absorbed dose had significant impact on
      the product quality and that the efficacy of absorbed dose is dependent on
      applied dose rates. In other words, a constant absorbed dose applied to the
      product is influenced by dose rate of the irradiation treatment.

PMID- 30228389
TI  - Bioprocess development and preservation of functional food from tomato seed
      isolate fermented by kefir culture mixture.
AB  - The aim of this work was to explore the use of protein isolate from tomato seed
      enriched with the sucrose and the ascorbic acid as a medium for the growth of
      kefir mixture culture to develop a new non-dairy functional food. Unstructured
      mathematical and logistic models were proposed to describe cell growth, kefiran
      production, nutriment consumption and antioxidant activity. It was found that the
      maximal cell mass in the culture reached 8.38 g L-1 after 24 h of fermentation. A
      significant amount of kefiran was also produced (0.65 g L-1). The kefir culture
      growth significantly decreased protein content and enhanced the antioxidant
      activity during varied fermentation through the production of bio active
      peptides. After 24 h of fermentation, IC50 value for protein isolate was
      estimated to be about 10.48 ug mL-1. The proposed models adequately described the
      changes during fermentation and as observed as a promising approach for the
      formulation of tomato seed-based functional foods. The preservation of the
      isolate was also investigated through a spray-drying process. The effect of spray
      drying on the viability of lactic acid bacteria and stability of protein content
      and the antioxidant activity of the powder was also carried out. Results showed
      that the spray-drying method has great potential for the synthesis of powder from
      the fermented isolate that are rich in desirable properties. However, it was
      appropriate to preserve the powder for 10 days at 37  degrees C for the
      preservation of protein functionality.

PMID- 30228390
TI  - Development of an extraction method for the determination of inorganic anions
      (chloride, sulfate and phosphate) in edible oils from different origins by ion
      chromatography.
AB  - The present work reports the development of ion chromatography conductivity based
      detection analytical method for the determination of some inorganic anions
      (chloride, sulfate and phosphate) in vegetable oils. The analytes were extracted
      from samples prior to injection into the chromatographic system, employing a
      simple two-step procedure. In the first step, 4.5 g of the sample was vigorously
      mixed with 15 mL of deionized water and then mixed for 15 min on a horizontal
      roller. Afterwards, the mixture was sonicated for 15 min in an ultrasonic bath.
      Then, the mixture was centrifuged for 15 min at 5000 rpm and, after filtration
      through a 0.22 MUm membrane, the aqueous phase was used for the determination of
      the analytes. A clean-up step was introduced in the analysis of olive oils in
      order to correct an increase of the baseline of the chromatograms. The limits of
      detection and quantification of the proposed method were, respectively, 0.005 and
      0.02 MUg g-1 for chloride, 0.02 and 0.06 MUg g-1 for phosphate and 0.008 and 0.03
      MUg g-1 for sulfate. Vegetable oils from corn, canola, soybean, sunflower and
      olive were analyzed and recovery tests (94.8 +/- 10.1% mean recovery) were
      performed to attest the accuracy of the proposed method.

PMID- 30228392
TI  - Evaluation of quality changes in nutritionally enriched extruded snacks during
      storage.
AB  - The aim of this study was to evaluate changes in the physical, chemical and
      sensory properties of a low fat-high protein, fiber enriched extruded snack. It
      was packed in metalized polypropylene/polyethylene (PP/PE) laminate pouches,
      under modified atmosphere packaging (MAP) with nitrogen flushing and without
      nitrogen flushing (control) and stored for a period of 22 weeks at 37 +/- 1 
      degrees C and 80% RH. MAP had significant impact on the moisture content, aw, TBA
      value, Hunter L* value and crispiness of the extruded snacks during storage. The
      moisture content of the snack significantly increased from 3.68 to 5.16% in
      control and from 3.66 to 4.31% in MAP. The oxidative rancidity in terms of TBA
      value of control sample increased from 0.02 to 0.07 while the product packaged
      under MAP, the value increased to 0.056. The sensory scores for flavour, color
      and appearance, texture and overall acceptability (OA) of the product
      significantly decreased during storage, but the product stored under MAP had
      better flavor (6.51) and OA scores (6.85) compared to control (5.58 and 6.04,
      respectively), after 22 weeks of storage. Thus, MAP tended to retard the storage
      induced changes and it could suitably be utilized for the delivery of low fat
      high protein, fiber enriched extruded snacks to the consumer, while keeping the
      sensorial acceptance of the product for 5 months.

PMID- 30228391
TI  - Identification and characterization of matrix components in spinach during
      QuEChERS sample preparation for pesticide residue analysis by LC-ESI-MS/MS, GC-MS
      and UPLC-DAD.
AB  - In this article matrix components in spinach were investigated in detail. The
      samples were prepared using two QuEChERS (quick, easy, cheap, effective, rugged
      and safe) methods, AOAC and CEN. Liquid chromatography-electrospray ionization
      tandem mass spectrometry (LC-ESI-MS/MS), gas chromatography-mass spectrometry (GC
      MS) and ultra performance liquid chromatography-diode array detector (UPLC-DAD),
      were applied for component identification. The strategies of identification by LC
      ESI-MS/MS include accurate mass spectra of the parent ion, comparison with
      previous literature data and investigation of the mass spectral decomposition
      pattern. Overall, fourteen components were identified by LC-ESI-MS/MS in each
      methods of AOAC and CEN, which were phytosteroids, flavonoids, fatty acids and
      fatty acid amides. Fifty components using AOAC method and fifty-seven components
      using CEN method were identified in GC-MS by comparing mass data with the
      National Institute of Standards and Technology (NIST, U.S.) database. The results
      indicate that the major components of the matrix are terpenoids, fatty acids and
      fatty acid esters. Moreover, three pigments (neoxanthin, violaxanthin and lutein)
      in the AOAC method and eight pigments (neoxanthin, violaxanthin, zeaxanthin,
      lutein, chlorophyll a, chlorophyll b, pheophytin a and beta-carotene) in the CEN
      method that gave a characteristics peak at 440 nm were identified by the UPLC
      DAD. According to the sample preparation condition using different amounts of
      graphitized carbon black (GCB) in this study, the AOAC method had higher matrix
      component removal efficiency than the CEN method. A better understanding of
      matrix components would increase the current knowledge for improvement of
      existing QuEChERS methodology, as well as contribute to new method developments.

PMID- 30228393
TI  - Machine vision based alternative testing approach for physical purity, viability
      and vigour testing of soybean seeds (Glycine max).
AB  - The conventional methods for seed quality testing have several limitations as
      they involve visual assessment and are destructive. In this context, a study was
      performed to assess the suitability of non-contact, non-destructive type imaging
      techniques such as visible imaging and X-ray imaging for conducting physical
      purity, viability and vigour tests of soybean seeds. The seeds that appeared
      healthy in external surface examination using visible tests as well as in
      internal assessment using X-ray tests were classified as sound seeds while the
      other seeds were marked as not-sound seeds. The obtained results were then
      correlated with the results of the standard germination tests. The high
      correlation results between the imaging tests and the standard conventional
      germination tests indicate the effectiveness and usability of the proposed image
      analysis based technique as an attractive alternative to the existing quality
      assessment methods for soybean seeds.

PMID- 30228394
TI  - Different sized wheat bran fibers as fat mimetic in biscuits: its effects on
      dough rheology and biscuit quality.
AB  - The aim of this study is to investigate the effects of various particle sized and
      different amount of plant fibers as fat mimetic for biscuit formulations instead
      of biscuit fat. The fibers with different particle sizes were obtained from wheat
      bran and used instead of fat in biscuit formulations. The texture, rheology and
      quality analyses of low-fat biscuit (30, 20 and 10% fat) were performed and
      compared with those of the full-fat control sample (40% fat). Results showed that
      wheat bran fiber with bigger particle size (Long Fiber, LF) were more favorable
      in terms of textural properties of the dough and the quality parameters of
      biscuits while the fibers with smaller particle size (Medium Fiber, MF and Small
      Fiber, SF) improved viscoelastic properties of dough similar to the control.
      Although the use of these fibers in the production of low-fat biscuits were
      suitable in terms of workability of dough increasing fiber content and/or
      reducing fiber size resulted in harder biscuits with lower spread ratio. This
      study showed that the texture of biscuits was greatly dependent on the texture of
      the dough.

PMID- 30228395
TI  - MIR spectroscopy as alternative method for further confirmation of foodborne
      pathogens Salmonella spp. and Listeria monocytogenes.
AB  - Listeriosis and Salmonellosis are two of the most common foodborne diseases.
      Consequently, an early and accurate detection of Listeria monocytogenes and
      Salmonella spp. in food products is a critical concern of public health policies.
      Therefore, it is of great interest to develop rapid, simple, and inexpensive
      alternatives for pathogen detection in food products. In this study, mid-infrared
      spectroscopy has been successfully used to confirm Listeria species and the
      presence of Salmonella isolated from food samples. This methodology showed to be
      very sensitive and could be a rapid alternative to detect these important
      pathogens, allowing to obtain results in a few minutes after previous growth in
      selective media, avoiding the confirmation procedures that delay the achievement
      of the results for up to 2 days.

PMID- 30228396
TI  - Changes in physico-chemical, astringency, volatile compounds and antioxidant
      activity of fresh and concentrated cashew apple juice fermented with
      Lactobacillus plantarum.
AB  - Changes in physico-chemical qualities (pH, total acidity, total and reducing
      sugar, total phenolic and vitamin C), astringency compounds (condensed and
      hydrolysable tannin), antioxidant activities [2,2-diphenyl-1-picrylhydrazyl
      (DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS)
      radical] and flavor volatile compounds in Lactobacillus plantarum-fermented
      cashew-apple-juice (CAJ) and 11.4  degrees Bx concentrated-cashew-apple-juice
      (CCAJ) was investigated. Total phenolics remained unchanged throughout
      fermentation period, whereas condensed tannins increased and hydrolysable tannins
      decreased indicating reduced astringency compounds. Antioxidant activity based on
      both DPPH and ABTS radical scavenging activities marginally declined in some
      stages but overall were sustained during fermentation. Although the DPPH. radical
      based antioxidant activity of fermented CAJ was greater than that of fermented
      11.4  degrees Bx CCAJ, a higher ABTS.+ radical scavenging activity was found in
      fermented 11.4  degrees Bx CCAJ, reflecting higher water soluble antioxidants.
      Results also indicated that DPPH. radical scavenging activity was positively
      correlated to vitamin-C and condensed tannins but not hydrolysable tannins.
      ABTS.+ radical scavenging activity was also positively correlated to condensed
      tannins and not hydrolysable tannins. The vitamin-C that increased during initial
      12 h fermentation, decreased from 2516 to 2150 mg AAE/L at the end of 72 h
      fermentation. Fermented CAJ had a remarkable sweet aroma with a fruity note of
      two major compounds; 3-methyl-1-butanol (14.20 * 107) and 2,6-dimethyl-4-heptanol
      (14.76 * 107). The high phytochemicals and volatile compounds in fermented CAJ
      indicated that it could serve as a functional beverage with potential health
      benefits with reduced astringency due to lower hydrolysable tannins.

PMID- 30228397
TI  - Study on formation of nitrated polycyclic aromatic hydrocarbons from different
      roasting condition in coffee.
AB  - Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) are organic, carcinogenic
      and mutagenic compounds that originate from the reaction of PAHs with NOx and OH
      radicals. In this study, an analytical method was developed, for the
      determination of seven nitro-PAHs and the method was applied to quantify the
      nitro-PAHs, in coffee model systems, prepared with coffee beans produced from
      three distinct locations and under various roasting conditions. Also, experiments
      were performed to study the effect of adding various amino acids on the formation
      of nitro-PAHs. The free radicals produced, were quantified by electron spin
      resonance (ESR), to assess their correlation with the formed nitro-PAHs. After
      extraction and cleanup, the nitro-PAHs in coffee were analyzed by gas
      chromatography/mass selective detection. In all heated coffee model systems, the
      addition of the amino acids, significantly increased the nitro-PAHs compared to
      the control. The ESR results were consistent with previous outcomes on the
      formation of nitro-PAHs.

PMID- 30228399
TI  - Shelf-life kinetic model for freeze-dried oranges using sensory analysis and
      luminance determination.
AB  - Physical (luminance) and sensory variables (color and taste) were used to analyze
      the aging of freezed-dried oranges slices, determining the influence of
      temperature and time on aging and evaluating the shelf-life. The highest value in
      the luminance distribution curve, especially useful when the color of the food
      products is not uniform, and the color and taste scores obtained in sensory
      analysis were used to evaluate the shelf-life. Different kinetics models were
      probed to explain the experimental results but only third-order kinetic model
      correlated the luminance as a function of time and temperature. This kinetic
      constant obtained depended on the temperature following an Arrhenius model,
      giving an activation energy equal to 208 kJ/mol (R2 = 0.9959). The correlation
      between physical (luminance) and sensory variables (color and taste) may be used
      to evaluate the shelf life of the orange slices, finding revealed that at 28 
      degrees C the shelf life may expected to be 10 years.

PMID- 30228398
TI  - Selection of non-Saccharomyces yeasts for orange wine fermentation based on their
      enological traits and volatile compounds formation.
AB  - In order to select the non-Saccharomyces yeasts for orange wine fermentation, the
      enological traits and volatile compounds formation of ten non-Saccharomyces yeast
      strains were evaluated through physicochemical methods and solid-phase
      microextraction coupled to GC-MS, respectively. The results indicated that non
      Saccharomyces yeast fermentation had lower maximum populations (7.8-8.0 Log
      cfu/mL), longer fermentation period (7-10 days), lower ethanol (4.13-7.79%),
      lower total acids (7.48-8.51 g/L) and higher volatile acids concentrations (0.08
      0.23 g/L) when compared with those of Saccharomyces cerevisiae fermentation.
      Hanseniaspora uvarum, Hanseniaspora opuntiae, Hanseniaspora occidentalis, Pichia
      kudriavzevii and Torulaspora delbrueckii were selected as candidates for orange
      wine fermentation with higher volatile compounds concentration, odor active
      values and sensory evaluation scores. This study will provide a valuable
      selection method of non-Saccharomyces yeasts for orange wine fermentation, and an
      approach to improve the flavor of orange wine or other fruit wine.

PMID- 30228400
TI  - Effects of sweeping frequency ultrasound pretreatment on the hydrolysis of zein:
      angiotensin-converting enzyme inhibitory activity and thermodynamics analysis.
AB  - In this study, we evaluated the effects of sweeping frequency ultrasound (SFU)
      pretreatment on the angiotensin-converting enzyme (ACE) inhibitory activity of
      zein hydrolysates and enzymatic hydrolysis thermodynamics. The solubility,
      surface hydrophobicity (Ho ), degree of hydrolysis (DH) of zein and ACE
      inhibitory activity of hydrolysates were determined. After SFU pretreatment, the
      solubility and Ho of zein were significantly increased. During the hydrolysis
      process, ultrasonic pretreatment significantly increased the DH of zein and the
      ACE-inhibitory activity of zein hydrolysates by 19.37 and 133.76%, respectively.
      First-order kinetics could be used to explain both traditional and ultrasonic
      assisted hydrolysis. In contrast to traditional hydrolysis, the reaction rate
      constants of SFU-assisted hydrolysis were largely increased by 82.76, 17.81,
      23.96, and 21.26% at hydrolysis temperatures of 293, 303, 313, and 323 K,
      respectively. For the thermodynamic parameters, SFU pretreatment decreased
      activation energy, enthalpy of activation, entropy of activation, and free energy
      of activation by 19.52, 20.63, 6.16, and 7.02% respectively. In conclusion, SFU
      pretreatment markedly enhanced the hydrolysis of zein, and this method could be
      applied to the protein proteolysis industry to produce zein peptides with high
      ACE inhibitory activity.

PMID- 30228401
TI  - Effects of blanching treatments on acrylamide, asparagine, reducing sugars and
      colour in potato chips.
AB  - This study aimed to determine the effect of combinations of blanching parameters,
      including blanching temperatures ranging from 65 to 85  degrees C and duration
      times ranging from 2 to 10 min, on reducing sugars, asparagine, acrylamide, and
      color levels of fried potato chips. Response surface methodology was used to
      develop response surface equations to estimate these effects. These latter were
      evaluated before and after a 3-month storage period of potato tubers at 10 
      degrees C. It was found that certain blanching parameters resulted in optimal
      maximum reductions of 64.2, 49.8, and 61.3% for reducing sugar, asparagine, and
      acrylamide, respectively. Analysis of variance (ANOVA) determined that blanching
      time had a more significant impact than blanching temperature. The blanching time
      that resulted in maximum reductions of asparagine, reducing sugars-and ultimately
      acrylamide-were in the range of 8.8-9.7 min at 68.7-75.0  degrees C. ANOVA also
      determined that after the 3-month storage period of potato tubers, variations in
      blanching time and temperature did not result in any significant differences in
      acrylamide formation in fried chips. Blanching consistently improved the
      appearance of the fried chip products, indicated by increases in L* value and
      decreases in a* values. The relationship between acrylamide formation and a*
      value was linear (R2 = 0.839), while the relationship between acrylamide
      formation and L* value was not (R2 = 0.375).

PMID- 30228402
TI  - Botanical influence on phenolic profile and antioxidant level of Italian honeys.
AB  - Honeybees directly transfer plant compounds from nectar into honey. Each plant
      species possesses a specific metabolic profile, the amount and the typology of
      plant molecules that may be detected in honey vary according to their botanical
      origin. Aim of the present work was the spectrophotometrical determination of
      concentration ranges of simple phenols and flavonoids in 460 several Italian
      monofloral honeys, in order to individuate specific intervals of plant
      metabolites for each typology of honey. Moreover, an LC-MS analysis was performed
      to determine amount of various secondary metabolites in the samples, with the
      purpose to use them as potential molecular markers in support to honey
      melissopalynological classification. As plant molecules have a strong reducing
      power, the antioxidant activity of the honeys was evaluated by two antiradical
      assays, DPPH and FRAP. The free radical scavenging effect of each monofloral
      group was correlated to the concentration of simple phenols and flavonoids, with
      the aim to deduce the existence of possible relationships between these
      parameters. In conclusion, dark honeys (Castanea sativa, honeydew, Erica sp. and
      Eucalyptus sp.) appeared to be the richest in secondary metabolites and,
      consequently, showed higher antioxidant activity. However, all analyzed
      monofloral honeys showed to be good sources of antioxidants.

PMID- 30228403
TI  - Interactions between whey protein and inulin in a model system.
AB  - Inulin is a commonly used prebiotic ingredients for functional food formulation.
      The effect of inulin on the gelation properties of whey protein was investigated
      using whey protein and inulin (WP/inulin) and polymerized whey protein and inulin
      (PWP/inulin) mixtures at different levels of protein (4-8%, w/v) and inulin (1
      5%, w/v). WP/inulin mixture was prepared by heating protein and inulin together
      while the latter by heating protein alone and then mixed with inulin. Both
      mixtures were analyzed for turbidity, zeta potential, particle size, and
      rheological properties. Dispersions became more opaque with increasing protein
      but there was no significant difference between the two mixtures. A small shift
      towards larger size and significantly decreased negative zeta potential with
      increasing inulin addition (1-5%) were observed for both mixtures. WP/PWP and
      inulin mixtures exhibited a shear thinning behavior. Transition temperature of
      whey protein increased with inulin addition. WP/PWP and inulin mixtures were
      induced into cold-set gels by calcium and the gels were analyzed for hardness.
      Hardness of WP/PWP and inulin gels increased with the increasing inulin. Results
      indicated that interactions between whey protein and inulin had impact on the
      gelation properties of whey protein regardless the way inulin added.

PMID- 30228404
TI  - Temperature dependent steady and dynamic oscillatory shear rheological
      characteristics of Indian cow milk (Desi) ghee.
AB  - Rheological characteristics of Desi ghee were investigated at 18, 24, 30 and 36 
      degrees C. The steady shear properties were evaluated by varying the shear rate
      from 0.01 to 100 s-1 and the dynamic shear properties were studied by varying
      strain and frequency sweep from 0.01 to 100% and 0.1 to 100 rad s-1,
      respectively. At the four selected temperatures, the ghee samples displayed non
      Newtonian shear thinning behavior with flow behavior index (n) ranging from 0.224
      to 0.911. As the shear rate increased from 0 to 100 s-1, the values of dynamic
      viscosity decreased from 54 to 8.14, 20.01 to 1.05, 1.33 to 0.295, and 3.02 to
      0.0025 Pa s at 18, 24, 30 and 36  degrees C, respectively. Out of four
      rheological models (Power-law or Ostwald-de Waele, Herschel-Bulkley, Casson, and
      Bingham model) fitted to the shear rate and stress data, the Ostwald model was
      found to be superior in predicting the shear rate-stress data at 18  degrees C,
      whereas Ostwald-de Waele and Herschel-Bulkley models predicted all the data
      points over the temperature range of 24-30  degrees C, as observed by the values
      of coefficient of determination (R2 ), standard deviation (SD), and relative
      deviation percentage (Rd ). The value of activation energy (EA ), as calculated
      from Arrhenius type equation, was found to be 1.98 * 106 kJ mol-1 over the entire
      temperature range. The study also revealed that the magnitudes of dynamic shear
      viscosity (eta*) were higher than those of the steady shear viscosity (eta) at
      the four temperatures, indicating that the Cox-Merz rule was not applicable to
      the ghee samples.

PMID- 30228405
TI  - Comparative study of hot air and vacuum drying on the drying kinetics and
      physicochemical properties of chicory roots.
AB  - The effect of the drying conditions on the retention quality for dried chicory
      roots (Cichorium intibyus L.) was investigated. Cubes of chicory roots were dried
      using hot air and vacuum dryers at 60 and 80  degrees C. Two different air
      velocities (0.2 and 0.7 m/s) were used in the hot air dryer, and two vacuum
      pressures (25 and 50 mmHg absolute) were set in the vacuum chamber. An exhaustive
      three dimensional mathematical model to describe mass transfer during drying of
      chicory roots of 1 cm of side was presented considering a polynomial
      functionality for the contraction kinetics. Experimental data obtained at
      laboratory scale were used to validate the proposed model showing good agreement
      between the experimental and estimated moisture profiles for both drying
      procedures. Moisture diffusivity was found to increase with the air drying
      temperature, velocity and vacuum pressure depending on the drying method.
      However, higher moisture diffusivity coefficients and lower activation energy
      values were obtained for the vacuum drying method. Samples dried using the vacuum
      drier at 60  degrees C and 25 mmHg presented better retention quality attributes,
      i.e., better rehydration, lower shrinkage and higher total phenolic content. The
      proposed mathematical model was able to satisfactorily predict the described
      behavior.

PMID- 30228406
TI  - Modelling dehydration of apricot in a non-conventional multi-component osmotic
      solution: effect on mass transfer kinetics and quality characteristics.
AB  - The quality and preservation of fresh-cut fruits can be improved by applying
      mild, non-thermal pre-treatments, such as osmotic dehydration (OD). The aim was
      to model the effect of OD on mass transfer and quality preservation. Apricot
      pieces were immersed in multi-component solutions comprising glycerol,
      erythritol, steviol glucosides and mineral salts, at various time-temperature
      conditions (25-45  degrees C for 3-240 min, wfruit/wsolution = 1/5). Water loss
      (WL), solid gain (SG), water activity (aw) as well as main quality indices
      (colour, texture) were measured during OD. OD apricot exhibited higher quality
      retention (acceptable level of colour change, increased firmness) suggesting that
      OD can be an effective pre-processing step in the production of innovative
      products. A second degree polynomial model was developed, describing the effect
      of processing conditions and glycerol concentration on WL, SG, aw, colour and
      texture of osmotically dehydrated apricots, and ANOVA was applied to identify the
      factors that significantly affect the aforementioned parameters.

PMID- 30228407
TI  - Effect of supercritical carbon dioxide processing on Vibrio parahaemolyticus in
      nutrient broth and in oysters (Crassostrea gigas).
AB  - This study aimed to evaluate the technical feasibility of supercritical carbon
      dioxide (sc-CO2) treatment for Vibrio parahaemolyticus inactivation in oysters
      (Crassostrea gigas) and in nutrient broth. For this purpose, a variable-volume
      reactor was used as experimental system and a 23 factorial design was adopted
      considering the mass ratio between carbon dioxide and the product, pressurization
      and depressurization rate and pressurization cycles. Through statistical analysis
      of the experimental data, the mass ratio of 1:0.8 (product:carbon dioxide),
      depressurization rate of 10.0 MPa/min and one cycle of pressurization was
      determined as the best process condition to eliminate V. parahaemolyticus, and
      this was the condition used for the inactivation kinetic analysis. Comparison
      between the inactivation kinetics of V. parahaemolyticus showed that the behavior
      of this microorganism inactivation depends on the environment in which it
      operates and its initial count. The results confirm that the supercritical carbon
      dioxide is effective in inactivating microorganisms in oysters, including
      pathogenic V. parahaemolyticus, demonstrating the potential of this technology in
      the food industry.

PMID- 30228408
TI  - Effects of sesame seed extract as a natural antioxidant on the oxidative
      stability of sunflower oil.
AB  - Natural and de-novo biosynthesized phyto-compounds have gained much significance
      because of their non-controversial nutritional, health and safety benefits as
      compared with chemically synthesized commercially rivalry antioxidants. However,
      none of natural de-novo biosynthesized phyto-compounds has been commercially
      available and used in customary food business and processing. In this study,
      efficacy of sesame seed extracts (SSEs) in stabilizing sunflower oil during
      storage has been studied. Fine powder of sesame seed was extracted in different
      solvents. The results showed that significant differences in extractability of
      different solvents and maximum extraction yield (29.48%) were achieved with
      methanol. The antioxidant components and capability of different extracts were
      further investigated and evaluated via total phenolic contents, DPPH radical
      scavenging activity and beta-carotene/linoleic acid calorimetric assays
      respectively. Being highest in yield and antioxidant potential, methanolic
      extract was used; three different concentrations of SSE (500, 750, and 1000 MUL)
      were added in 100 mL of sunflower oil to further evaluate its oxidative
      stability. Sensory and oxidative analysis of baked product from these groups was
      also evaluated.

PMID- 30228409
TI  - Assessment of physicochemical characteristics and modifications of pasting
      properties of different varieties of maize flour using additives.
AB  - Maize cereal has potential to be used for food purpose but lack of viscoelastic
      behaviour that limits its use for this purpose. Therefore, present study on
      modification of pasting properties of maize flour using different additives was
      carried out. Flours of three maize varieties (PMH1, JL3459 and Buland) with and
      without additives (guar gum, xanthan gum, whey protein concentrate and potato
      starch) were analysed for physico-chemical and pasting properties. Maize (PMH1)
      had maximum thousand kernel weight (312.47 g), bulk density (0.80 g/ml), force to
      rupture (68.54 kg) and contained the highest starch (67.70%) and fat (5.08%)
      among the three varieties. Different levels of guar gum (0-1.0%), xanthan gum (0
      1.0%), whey protein concentrate (0-15.0%) and potato starch (0-10.0%) were
      incorporated in flours from three maize varieties. Results showed that guar gum
      1.0% (w/w basis) and xanthan gum 1.0% (w/w basis) incorporation led to the
      highest peak and final viscosity whereas whey protein concentrate and potato
      starch were not selected because of negative effect on these properties. These
      additives can be used as binding agent in chapati and other maize products.

PMID- 30228410
TI  - Evaluation of different Saccharomyces cerevisiae strains on the profile of
      volatile compounds in pineapple wine.
AB  - Yeast strain plays a central role in the formation of aroma and flavour of fruit
      wine. The effect of four commercial Saccharomyces cerevisiae strains (D254, VIC,
      BV818 and CECA) on volatile compounds of fermented pineapple (Ananas comosus L.
      Merr.) juice was investigated. Alcohols and esters were the most abundant groups
      in terms of the amounts of identified volatiles in four pineapple wines, followed
      by acids and sulphur compounds. Different S. cerevisiae strains possess various
      capacities to release or synthesize volatiles during pineapple wine fermentation.
      For global aroma, strain D254 yielded the highest total number and concentration
      of volatiles and could be used as a starter culture for the making of intense
      pineapple wine. Strain BV818 produced wine with the highest amounts of volatiles
      with OAVs > 1 and scored the highest in global aroma. Thus, BV818 might be the
      appropriate strain that could impart characteristic aromas and enhance wine
      complexity. The relative content of esters formed by strain VIC was higher than
      that yielded by the other strains. Strain CECA produced the highest relative
      contents of alcohols, aldehydes and ketones. However, VIC and CECA were not ideal
      starter cultures because of their low sense scores. This study provided a
      foundation for the production of pineapple wine with the desired flavour profile.

PMID- 30228411
TI  - Influence of protein source on characteristics and quality of gluten-free
      cookies.
AB  - Proteins are essential nutrients in the diet, with the recommended amount of
      daily protein consumption varying for people with different health status and
      activity level. Cookies could be an adequate carrier of proteins because of their
      great acceptability. The aim of this study was to analyse the effect of flour
      substitution with different types of protein (pea, potato, egg white and whey) in
      gluten-free cookies. Hydration properties, dough rheology, cookie characteristics
      (protein content, dimensions, texture) and sensory acceptability were studied.
      The hydration properties of mixtures with protein were lower than the control,
      with the exception of pea protein. As for results from rheological analysis, G'
      and G" values for pea and potato protein were similar to the control, while egg
      white and whey protein had lower values. Addition of egg white and whey protein
      respectively, produced harder and wider cookies. The addition of potato protein
      yielded cookies with darker edges, however, pea protein did not lead to any
      significant change in cookie parameters. Sensory evaluation showed that the
      addition of pea protein produced cookies with the same scores as the control
      sample, signifying that cookies with added pea protein had the best
      acceptability.

PMID- 30228412
TI  - Thermodynamics of sorption isotherms and storage stability of spray dried
      sweetened yoghurt powder.
AB  - Sorption isotherm is a quantitative approach to predict the shelf life of dried
      foods. Adsorption isotherms of spray dried sweetened yoghurt powder (SYP) were
      determined by static gravimetric technique at 20, 30, 40 and 50  degrees C. The
      data obtained were fitted to eight different sorption models. A non-linear least
      square regression analysis was adopted to evaluate the model constants. The
      experimental sorption data were best fitted to four parameter Peleg model. The
      monolayer moisture contents found from GAB model were 4.88, 4.54, 3.86 and 3.52%
      at 20, 30, 40 and 50  degrees C, respectively. The maximum net isosteric heat of
      sorption and sorption entropy of SYP were 9.399 kJ/mol and 20.28 J/mol K,
      respectively. The Gibb's free energy change for sorption was in the range 3436.19
      303.91 J/mol. The storage stability in terms of moisture content, thiobarbituric
      acid, free fatty acid, hydroxymethyl furfural values and starter counts of SYP
      packed in aluminium laminated polyethylene (ALPE) and low density polyethylene
      (LDPE) were studied along with their change kinetics. The relationship between
      the water vapour permeability of packaging materials and adsorbed moisture
      (determined from GAB equation) in powder was used to predict the shelf life and
      was predicted as 28 and 44.44 days in LDPE and ALPE pouches, respectively.

PMID- 30228413
TI  - Extraction and application of chia mucilage (Salvia hispanica L.) and locust bean
      gum (Ceratonia siliqua L.) in goat milk frozen dessert.
AB  - A complete factorial design (23) was used to determine the influence of chia
      mucilage concentration (CM), locust bean gum (LBG) and base maturation time (BMT)
      on 14 formulations of goat milk frozen dessert. Chia mucilage was obtained by
      chia grain hydration (1:40) under stirring for 2 h, at 80  degrees C and pH of
      9.0. The samples were centrifuged, as well as lyophilised to compare yields. The
      extraction yield of lyophilised CM was lower than 10%. The addition of LBG and CM
      at higher levels, influenced by BMT, increased the moisture content and the
      apparent viscosity of the base mixture. These formulations presented higher
      values for texture and lower of overrun due to the difficulty of incorporating
      and stabilising bubbles during whipping and freezing processes. The melting rate
      was also dependent on the variables analysed, and a delay in melting was
      observed, even in the formulations with lower fat content. CM increased the
      luminosity parameter proportionally to its content and provided a significant
      reduction of fat (up to 3.10 g 100 g-1) and energy value. The application of CM
      reduced the texture value, which was an interesting technological characteristic
      for frozen dessert.

PMID- 30228414
TI  - Sacha inchi seeds from sub-tropical cultivation: effects of roasting on
      antinutrients, antioxidant capacity and oxidative stability.
AB  - Due to the strong bitter taste, sacha inchi seeds are usually consumed after
      roasting, which also contributes to the elimination of antinutrients. Sacha inchi
      plants fully adapted to cultivation under sub-tropical climate conditions were
      produced in southeastern Brazil. Our main goal was to evaluate the effect of dry
      heating (roasting) on the antinutrient content of these seeds. We also
      investigated the effects of the applied roasting treatments on the antioxidant
      activity, proximate composition and oxidative stability of the seeds. To the best
      of our knowledge, this is the first report on antinutrients of sacha inchi seeds
      cultivated under sub-tropical conditions, outside their native tropical
      environment. Except for saponins, which are not heat-labile compounds, the
      contents of all assessed antinutrients continually reduced with the increase in
      roasting temperature. Roasting improved antioxidant activity and phenolic content
      in the seeds at the highest temperature. Oxidation changes occurred in the seed
      oil, and they increased with temperature. However, maximum peroxide value was
      within the acceptable consumption limits. As a conclusion, roasting treatments
      can be applied to minimize the antinutrient potential in sacha inchi seeds.
      Knowledge on the composition and proper processing of sacha inchi cultivated
      under sub-tropical conditions may support future efforts focused on the
      development of new production areas.

PMID- 30228415
TI  - Effects of ultraviolet C, controlled atmosphere, and ultrasound pretreatment on
      free ferulic acid in canned sweet corn kernels.
AB  - Because canned sweet corn kernel (CSCK) products are subject to high market
      competitiveness, producing them with a higher content of free ferulic acid (FFA),
      a functional ingredient, using non-thermal and green technologies may be an
      alternative solution for Thai exporters. This study aimed to investigate the
      effects of pre-canning ultraviolet C (UVC), controlled atmosphere (CA), and
      ultrasound treatments on the FFA content, texture, and colour of CSCKs. UVC
      irradiation (0, 1.94 and 4.01 kJ/m2) was tested in combination with storing corn
      under CA at %O2:%CO2:%N2 ratios of 21:0.03:78, 3:10:87, and 3:15:82 before
      canning. Based on the FFA content, two UVC-CA pretreatments were selected for the
      ensuing experiment. The effects of the selected UVC-CAs in combination with 0,
      10, or 20 min of 35 kHz ultrasound before canning were measured. The FFA content,
      moisture, texture, and colour of the CSCKs treated with the nine UVC-CA
      combinations were not significantly different. Corn irradiated with 1.94 kJ/m2
      UVC and stored under 3:15:82 %O2:%CO2:%N2 before canning exhibited the highest
      FFA content, followed by corn treated with no UVC and stored at 3:15:82
      %O2:%CO2:%N2. Corn treated with ultrasound combined with the two selected UVC-CA
      treatments showed no differences in FFA content, moisture, texture, or colour.
      Corn kernels treated with UVC-CA-ultrasound had a higher FFA content than
      untreated kernels. UVC-CA-ultrasound pretreatment showed a trend of increasing
      CSCK FFA content with no change in physical properties. Thus, UVC-CA-ultrasound
      pretreatment appears to be an alternative process that might add value to CSCKs
      by increasing FFA content.

PMID- 30228416
TI  - Influence of different by-products addition on sensory and physicochemical
      aspects of Primosale cheese.
AB  - Food industry produces considerable amounts of by-products that represent a
      severe problem from both economic and pollution points of view. The bioactive
      compounds still present in food by-products offer the possibility to re-use them
      to develop added value products. In the current work some by-products were
      incorporated into curd during production of Primosale cheese. Specifically, two
      concentrations (i.e., 50 and 100 g Kg-1) of flours from different by-products
      (i.e., red and white wine grape pomace; tomato peel, broccoli and artichokes by
      products), as source of dietary fibres and bioactive compounds were tested. The
      swelling and water retention capacity of flours, in addition to physicochemical
      characteristics of cheese (cheese weight loss, dry substance in the whey, cheese
      moisture content and pH), bioactive compounds (total phenolic compounds, total
      flavonoids and antioxidant activity) and sensory profile were evaluated. Results
      highlighted that addition of by-products to Primosale cheese improved the
      nutritional properties and some sensory attributes such as friability and
      adhesiveness. Among the tested by-products, the most attractive result was
      obtained for Primosale cheese with artichoke by-products.

PMID- 30228418
TI  - Non-invasive determination of surface features of banana during ripening.
AB  - Ripening of dessert banana (Musa sap.) is associated with changes in colour
      (green to yellow starting from the cente), softening, and surface features. These
      have mostly been investigated using distinct technologies. Hence, here changes in
      surface features were examined with two novel, non-invasive techniques: a luster
      sensor and a 3D profilometer. The profiler measures the 3D surface
      characteristics of an area, rather than a single profile line, and corrects data
      for curvature of the fruit. The luster sensor detected an increase in glossiness
      from stage 3 (green) to stage F7a (ripe) of ca. 35%, followed by a decrease in
      glossiness from stage F7a to F7b (overripe). The profilometer provided visual and
      parametric roughness values (Ra) for ripening. Cavendish bananas showed an
      increase from 2.5 to 6.6 um during ripening stage 3 (green) to stage 7b
      (overripe). Another roughness value, Rz, increased concomitantly from 13.1 um at
      stage 3 (green) to 26.9 um at stage F7b (overripe). The study showed that the
      centre of the fruit was the best region for surface imaging, because it was the
      most advanced ripening part of the banana fruit, easily curved, and the region of
      the fruit can be accessed when a carton was opened. This study shows that it is
      now possible to monitor the changes in surface glossiness and roughness during
      the ripening of Cavendish bananas using two novel non-invasive technologies. The
      compact luster sensor may become a component of a portable probe and manual
      control of packing units. Differences in the predicted green life can be used to
      prioritize containers for unloading in the discharge port or to implement quality
      based warehouse management strategies. Containers that arrive at banana ripening
      rooms before their green life ends, can be re-routed, in addition to the present,
      colour-based ripening scale.

PMID- 30228417
TI  - The effects of baking conditions on acrylamide content in shortcrust cookies with
      added freeze-dried aqueous rosemary extract.
AB  - The aim of the present study was to determine the effects of baking air humidity
      and dough supplementation with freeze-dried aqueous rosemary extract on
      acrylamide content in shortcrust cookies, as well as on their antioxidant
      properties and phenolic composition. Shortcrust cookies were baked at 170 
      degrees C in dry or humid (90%) air using 0.1, 0.2, or 0.5% of rosemary extract,
      and were compared to control samples without the extract. Acrylamide
      concentration in the obtained products ranged from 22.49 to 28.38 ug kg-1.
      Furthermore, cookies baked in humid air had less acrylamide (by 6% on average)
      than those baked in dry air, irrespective of extract content. On the other hand,
      a significant relationship was found between humidity conditions and total
      phenolic content in the final products. Shortcrust cookies containing 0.5% of
      rosemary extract and baked in humid air revealed the best antioxidant properties
      as their total polyphenol content was approx. Three times higher than that in
      control samples. Furthermore, shortcrust cookies with 0.5% of rosemary extract
      showed superior DPPH radical scavenging capacity.

PMID- 30228419
TI  - The effects of conventional heating on phenolic compounds and antioxidant
      activities of olive leaves.
AB  - Phenolic compounds, antioxidant activities and total phenolic contents of leaves
      from different olive varieties (Gemlik, Kalamata, Yaglik and Sariulak) were
      evaluated after conventional drying at different temperatures (50, 60, 70 and 80 
      degrees C). The drying process resulted in non-significant effects on olive
      leaves. The phenolic contents however, varied with drying temperature. The
      contents of minor total phenolics in Gemlik, Kalamata and Sariulak leaves were
      1457.6, 1899.3 and 2179.8 mg GAE/100 g, respectively when dried at 60  degrees C.
      The highest total phenolic reduction (23.2%) was observed in Kalamata leaves
      after drying at 80  degrees C. The major phenolic compounds in olive leaves were
      gallic acid (101.2-439.7 mg/100 g), 3,4-dihydroxybenzoic acid (66.7-460.4 mg/100
      g), (+)-catechin (39.2-667.8 mg/100 g), 1,2-dihydroxybenzene (15.8-584.8 mg/100
      g) and quercetin (33.1-277.7 mg/100 g). It was observed that olive leaves from
      different varieties are rich in phenolic compounds which are sensitive to heat
      and varied with drying temperature.

PMID- 30228420
TI  - The effect of Laurus nobilis L. essential oil and different packaging systems on
      the photo-oxidative stability of Chemlal extra-virgin olive oil.
AB  - This study was performed to determine the effect of the addition of Laurus
      nobilis L. essential oil (EO) (at 0.01% v/v) and of the packaging material (brown
      and transparent glass or PET) on the oxidative stability of Algerian extra-virgin
      olive oil (EVOO) stored for 90 days at 25 +/- 2  degrees C under continuous
      exposure to fluorescent light (~ 900 lux). Control and enriched EVOO was analysed
      after 30, 60 and 90 days for various parameters. Bio-enrichment of EVOO with EO
      combined with packaging in brown glass enabled maintenance of the highest amounts
      of chlorophyll and carotenoids after 90 days of accelerated photo-oxidation. The
      lowest total phenols content was found in EVOO without EO packed in transparent
      glass. EO enrichment and brown packaging preserved higher levels of antioxidant
      activity but could not preserve the oxidation indices until the end of the period
      of light exposition.

PMID- 30228421
TI  - Effect of olive oil on the preparation of nanoemulsions and its effect on aroma
      release.
AB  - The present study focused on the effect of olive oil on Ostwald ripening of
      flavor nanoemulsions. The release of the aroma compounds from the nanoemulsion
      system was also investigated. The results showed that the droplets size of the
      nanoemulsions decreased sharply first and then kept stable with the increase of
      Tween 80. The optimum surfactant/cosurfactant (Km) ratio was determined at 7:1.
      The average particle size of nanoemulsion was 39.22 nm. The polydispersity index
      (PDI) was 0.242 nm, and the particle size distribution was in the range of 20-150
      nm at the optimum Km. The stability of the nanoemulsions was improved after the
      addition of olive oil, and it increased noticeably with the increase of olive
      oil. The addition of olive oil could help to stabilize the emulsions and hamper
      Ostwald ripening. All the 11 aroma compounds in the nanoemulsions were detected
      after 24-h storage. While only 5 aroma compounds were found after 48-h storage,
      and alpha-pinene and beta-myrcene were the only two aroma compounds detected
      after 72-h storage with low contents of 1.41 and 0.5 mg/L. The addition of olive
      oil inhibited the release of the aroma compounds from the nanoemulsion system.
      The released ethyl acetate was reduced by 48% after the addition of 10% olive
      oil. Significant decrease on the release of alpha-pinene and nonanal was observed
      after the addition of 3% olive oil. And the decrease was also observed on the
      release of beta-myrcene, D-limonene, alpha-terpineol, decanal and eugenol when
      the olive oil content was >= 5%. However, benzyl alcohol, beta-ionone and 1
      octanol showed no significant changes with the increase of olive oil. This
      indicated that the addition of olive oil could provide greater retention of the
      aroma compounds in the nanoemulsions.

PMID- 30228422
TI  - Comparative milk metabolite profiling for exploring superiority of indigenous
      Indian cow milk over exotic and crossbred counterparts.
AB  - This study was planned to identify differences in the milk metabolite composition
      of Indian (Sahiwal), exotic (Holstein-Friesian) and their crossbred cows in
      intensive system of management. To mimic the management system of ancient India,
      indigenous cattle under extensive system (zero input) were also included.
      Holstein-Friesian (HF) had significantly higher amount of saturated fatty acids
      (SFA, 76.3%) as compared to the crossbred (73.3%) and Sahiwal (68.0%). HF had the
      highest concentration (42.7%) of hypercholesterolemic fatty acids and the maximum
      value (68.5) of athrogenecity index (AI). Sahiwal had the highest proportion
      (32.1%) of total unsaturated fatty acids (UFA). Mineral, vitamin, n-3 fatty acids
      and total amount of essential amino acids did not vary across the three groups.
      Milk of indigenous cattle maintained only on grazing had more favorable nutrient
      profile. It had low SFA (61.4%), high UFA (38.6%) and higher concentrations of
      both monounsaturated fatty acids (31.4%) and polyunsaturated fatty acids (7.2%).
      The n-6/n-3 ratio (2.7) and the AI (33.9) were significantly lower. Significantly
      higher concentrations of minerals (Zn, Fe, P and Cu) and vitamins except vitamin
      B5 were recorded in their milk. The study revealed that milk metabolite
      characteristics can be used to promote indigenous cattle.

PMID- 30228423
TI  - Optimization and characterization of an extruded snack based on taro flour
      (Colocasia esculenta L.) enriched with mango pulp (Mangifera indica L.).
AB  - The aim of this study was to optimize and characterize an extruded snack made
      with taro flour and mango pulp. A central experimental design composed of the
      following three variables was used: mango pulp proportion (MPP = 0-10 g/100 g) in
      taro flour, feed moisture content (FMC = 16-30 g/100 g) and extrusion temperature
      (zone 4 of extruder) (T = 80-150  degrees C) using a single-screw extruder with a
      compression screw ratio of 3:1. Increasing FMC values decreased the torque,
      pressure, specific mechanical energy (SME), expansion index (EI), water
      solubility index and pH values and increased the residence time, bulk density
      (BD), hardness and total colour difference. Increasing T values led to a decrease
      in the torque, pressure, BD and hardness values, while increasing MPP values only
      caused a significant increase in the hardness values and beta-carotene content
      and a decrease in the pressure value. The optimal extrusion conditions were T =
      135.81  degrees C, FMC = 18.84 g/100 g and MPP = 7.97 g/100 g, with a
      desirability value of 0.772, to obtain a snack with EI = 1.52, BD = 0.66 g/cm3,
      hardness = 24.48 N, beta-carotene content = 99.1 MUg/g and SME = 428.54 J/g. The
      mango pulp is an available and economical source of beta-carotene for the
      enrichment of extruded expanded taro snacks.

PMID- 30228424
TI  - Chitosan films incorporated with Thymus capitatus essential oil: mechanical
      properties and antimicrobial activity against degradative bacterial species
      isolated from tuna (Thunnus sp.) and swordfish (Xiphias gladius).
AB  - Chitosan-based coatings and films have been widely studied, demonstrating to be
      an efficient and eco-friendly approach to extend the shelf life of food products.
      The effect of incorporating Thymus capitatus essential oil (TCEO) at different
      concentrations (0.5, 1.0, and 1.5% w/w) on physical, mechanical and antimicrobial
      properties of chitosan films was studied. The antimicrobial activity of the films
      was evaluated by agar diffusion method, against 23 spoiling microorganisms
      isolated from tuna and swordfish (ten Shewanella baltica, one S. morhuae, one S.
      putrefaciens, two Pseudomonas fluorescens, two P. fragi, five Serratia spp., one
      Aeromonas molluscorum, and one Acinetobacter radioresistens) and Shewanella
      putrefaciens ATCC 49138. The films exerted antimicrobial activity against all the
      tested strain, although not proportional to increasing TCEO concentration. In
      particular, S. baltica was the most sensitive species and the inhibition was
      stable after 72 h. In general, TCEO incorporation in chitosan films,
      significantly (p < 0.05) decreased the water permeability (from 0.577 +/- 0.060
      gmm/kPahm2 at 61% R.U. for chitosan to 0.487 +/- 0.037 gmm/kPahm2 for the film
      with 1.5% TCEO), the elongation at brake (from 27.322 +/- 2.35% for chitosan to
      14.695 +/- 3.99% for the film with 1.5% TCEO) and increased the tensile strength
      (from 1.697 +/- 0.16% for chitosan to 19.480 +/- 2.86% for the film with 1.5%
      TCEO). Moisture content and water contact angle of the films also showed a
      similar trend with TCEO introduction, because of crosslinking reaction among the
      polymer chains and TCEO components. Scanning electron microscopy confirmed
      structure-properties relationships. These results suggest chitosan films
      incorporated with TCEO as an alternative treatment to inhibit the growth of
      degradative bacteria with potential application in the fish industry. The
      importance of testing more than one strain of the same bacteria species to
      evaluate the effectiveness of chitosan-essential oils coatings was also
      demonstrated.

PMID- 30228425
TI  - Molecular modification, expression and purification of new subtype antioxidant
      peptide from Pinctada fucata by recombinant Escherichia coli to improve
      antioxidant-activity.
AB  - The aim of this study was to establish a system for the efficient expression and
      purification of new subtype of antioxidant peptide from Pinctada fucata meat
      (NPFMAP), which is designed by molecular modification technology based on the
      sequence of purified and identified antioxidant peptide from Pinctada fucata meat
      (PFMAP, Gly-Ala-Gly-Leu-Pro-Gly-Lys-Arg-Glu-Arg), and to better understand the
      relationship between structure and antioxidant activity. Meanwhile, gene codon
      usage was optimized and the glutathione S-transferase (GST) tag of pGEX-6P-1 was
      added to facilitate expression and purification NPFMAP in Escherichia coli. The
      results of antioxidant activity assay in vitro showed a higher antioxidant
      activity in NPFMAP than that in enzymatic hydrolysis digested or chemically
      synthesized PFMAP. In particular, the DPPH scavenging radical activity increased
      by about 4.7 times after molecular modification. Structural bioanalysis indicated
      that new subtype antioxidant peptide had spatial conformation and good
      hydrophilic after modification, which was confirmed by antioxidant activity
      assays. Thus, the proposed method could be used to obtain NPFMAP with high
      antioxidant activity.

PMID- 30228427
TI  - Investigation of nitrite alternatives for the color stabilization of heme-iron
      hydrolysates.
AB  - This study investigates the potential of novel heme-ligand complexes, derived
      from heme-iron isolated from porcine hemoglobin by enzymatic hydrolysis, to use
      as pigments for meat products. Five alternatives to sodium nitrite were
      identified as possible heme ligands and stabilizing agents of the red
      conformation of heme. The effects of 4-methylimidazole, methyl nicotinate,
      pyrrolidine, piperidine, pyrazine and sodium nitrite (as comparative benchmark)
      on the color of heme-iron extract and pure hemin standard were studied in
      solution. The ligand affinity and heme-ligand stability was assessed over time in
      solution by UV-Vis absorbance spectroscopy and CIELAB color space parameters. The
      CIE redness score a* was used as a single measurement to propose a predictive
      model based on the following parameters: heme source (heme-iron extract or hemin
      standard), heme-to-ligand molar ratio (1:20 to 1:300), and storage time (up to 32
      days). The optimal concentration at which each ligand can be added to either heme
      source, as well as the stability of the red color of the formed heme-ligand
      complexes in-solution was determined. Heme-iron extract-derived samples showed
      increased redness and color stability as compared to their hemin counterparts. No
      ligand showed as much affinity for heme as sodium nitrite. As the most promising
      ligand candidates, methyl nicotinate and 4-methylimidazole started to show color
      changes at a 1:50 molar ratio, but higher amounts (1:100 and 1:300, respectively)
      were required to attain the maximum redness possible with the highest stability.

PMID- 30228428
TI  - Effect of exogenous spermine on chilling injury and antioxidant defense system of
      immature vegetable soybean during cold storage.
AB  - The effect of exogenous spermine on chilling injury (CI) and antioxidant defense
      system of immature vegetable soybean (Glycine max L.) during cold storage were
      investigated. Freshly harvested immature soybeans were treated with 0.8 mmol/L
      spermine at room temperature for 20 min and then stored at 5 +/- 1  degrees C or
      1 +/- 1  degrees C and 85-95% relative humidity for up to 60 days. Results showed
      that exogenous spermine alleviated the CI, delayed the gradual decreasing
      activities of superoxide dismutase (SOD) and catalase, and maintained a
      favourable balance in reactive oxygen species levels at storage period. Although
      cold temperature (1 +/- 1  degrees C) inhibited the synthesis of l-(malonylamino)
      cyclopropane-l-carboxylic acid (MACC), raised ethylene production, and resulted
      in membrane damage, exogenous spermine obviously hindered the accumulation of 1
      aminocyclopropane-1-carboxylic acid (ACC). It was concluded that exogenous
      spermine alleviated CI of cold-stored immature soybeans through regulating the
      antioxidant system and ACC metabolism.

PMID- 30228426
TI  - Determination of free amino acids in tea by a novel method of reversed-phase high
      performance liquid chromatography applying 6-Aminoquinolyl-N-Hydroxysuccinimidyl
      carbamate reagent.
AB  - We describe a novel analytical method for quantification of free amino acids in
      tea using variable mobile phase pH, elution gradient and column temperature of
      reversed-phase high-performance liquid chromatography (RP-HPLC). The study of
      mobile phase pH 5.7 was chosen to simultaneous quantification of 19 free amino
      acids in tea, while it improved maximum resolution of glutamine, histidine and
      theanine. Elution gradient was adapted for enhancing the solution of free amino
      acids, mainly because of adjustment of mobile phase A and B. The column
      temperature of 40  degrees C was conducive to separate free amino acids in tea.
      The limit of detection (LOD) and limit of quantitation (LOQ) of this method were
      in the range of 0.097-0.228 nmol/mL and 0.323-0.761 nmol/mL, respectively. The
      relative standard deviation of intraday and interday ranged in 0.099-1.909% and
      3.231-7.025%, respectively, indicating that the method was reproducible and
      precise, while recovery ranged between 81.06-112.78%, showing that the method had
      an acceptable accuracy. This method was applied for the quantification of free
      amino acids in six types of tea. Multivariate analysis identified serine,
      glutamine, theanine and leucine as the most influencing factor for classify among
      analyzed sample.

PMID- 30228429
TI  - In vitro antibacterial activity of nut by-products against foodborne pathogens
      and their application in fresh-cut fruit model.
AB  - Aqueous extract of nut by-products (cashewnut shell, coconut shell, and peanut
      hull) were studied for their physicochemical properties, antibacterial activity
      and food preservation potential in an artificially inoculated fresh-cut fruit
      (papaya) model. Physicochemical characteristics revealed the colour, odor, nearly
      neutral pH (6.67-6.83), high water solubility (69.18-82.63%) and total phenolic
      content (1130.54-2403.41 mg GAE/100 g) of the extracts. The antibacterial
      property of the extracts evaluated by zone of inhibition assay revealed that
      cashew nut shell extract had a strong inhibition effect on Escherichia coli (18
      mm), Listeria monocytogenes (18 mm), and Salmonella enterica (16 mm). Food
      preservative effect of extracts was examined in an artificially inoculated fresh
      cut papaya model, and both cashewnut and coconut shell extracts significantly
      reduced the population of the above mentioned foodborne pathogens. However, when
      compared to coconut shell extract, the application of cashewnut shell extract was
      found to affect the sensory property of the fresh-cut fruit as darkening of the
      cut fruit was observed. So, the coconut shell extract could be considered as a
      natural source of antibacterial agent for food preservative applications.
      Phytochemical investigation through LC-MS/MS technique revealed that luteolin as
      the major constituent of coconut shell extract.

PMID- 30228430
TI  - Low pressure superheated steam drying of onion slices: kinetics and quality
      comparison with vacuum and hot air drying in an advanced drying unit.
AB  - Pungency is important characteristics of onion and during processing it is
      generally reduces. Low pressure superheated steam drying (LPSSD) is gaining
      importance due to energy and product benefits. It results in better retentions of
      bioactive components. So, in current study onion slices were dried using low
      pressure superheated steam, and compared with vacuum and hot air drying at
      different temperature in NIFTEM advance drying unit. Among the selected models,
      Page's model gave a better prediction and satisfactorily described drying
      characteristics of onion slices. The Activation energy was found to be 41.87
      kJ/mol in LPSSD. Quality of product, i.e. retention of color, rehydration ratio,
      thiosulphinate content, total phenol content and antioxidant activity, were
      better at 70  degrees C using LPSSD, at 60  degrees C using VD and HAD, as
      compared to other drying temperature in respective drying technologies used.
      Significant differences in quality of the dried product were also observed due to
      drying temperature in different drying techniques.

PMID- 30228431
TI  - Effect of type and quality of milk on heat induced protein-protein interactions
      in khoa.
AB  - The present study was carried out to evaluate the effect of developed acidity and
      subsequent neutralization of milk (cow/buffalo) on heat induced protein-protein
      interactions occurring at various stages during khoa preparation. Protein-protein
      interactions were studied in terms of surface hydrophobicity (Fmax), sulfhydryl (
      SH) group and SDS PAGE. As milk progressed to boiling stage, increase in Fmax and
      decrease in -SH content was observed. Khoa prepared from cow milk had
      comparatively higher values for Fmax and lower values for -SH group. Fmax was
      observed to be highest in acidic samples followed by neutralized and fresh
      samples. While considering -SH group, maximum values were observed in neutralized
      samples followed by acidic and fresh samples of both milk and khoa. However, no
      visible difference was observed in SDS PAGE patterns of casein fractions isolated
      from different types of samples. The bands of beta-lg and alpha-la did not
      resolve clearly in the khoa samples due to high heat treatment involved in its
      preparation, indicating intense denaturation of whey proteins especially in
      neutralized samples where an alkaline medium resulted in strong binding between
      casein and whey proteins. The quality of milk also resulted in altered heat
      induced protein-protein interactions in khoa.

PMID- 30228432
TI  - Proximate and mineral composition of Kadamba (Neolamarckia cadamba) fruit and its
      use in the development of nutraceutical enriched beverage.
AB  - Neolamarckia cadamba, commonly known as Kadamba, is one of the economically
      important trees, which is being exploited for paper, pulp and wood industries,
      however uses of its fruits are not reported. In the present investigation the N.
      cadamba fruits were analysed for their proximate and mineral content at different
      stages of maturity, and the ripe fruit was used for nectar preparation. Proximate
      analysis of the ripe edible fruit showed that it is rich in fat (2.4%) and
      proteins (2.1%), and has calorific value of 103.7 kcal/100 g. The nectar prepared
      from the ripe fruits showed mean overall acceptability score of more than 6
      indicating its suitability for nectar preparation. The shelf life of nectar was
      found to be 150 days at ambient conditions (28 +/- 3  degrees C). The nectar was
      rich in minerals and antioxidants, and can be recommended for consumption by
      various age groups. However, studies are required to ascertain its physiological
      effect on consumers.

PMID- 30228433
TI  - UPLC-DAD quantification of chemical constituents of Potentilla atrosanguinea
      roots and their antioxidant activity.
AB  - Potentilla atrosanguinea, native to Himalayan region, is well known for its
      curative effects in traditional medicinal system. An ultra performance liquid
      chromatography-diode array detection method for the quantification of
      constituents of root part of P. atrosanguinea has been developed along with
      antioxidant activity evaluation. A simple and sensitive quantification method
      developed for seven compounds however only four compounds; p-coumaric acid (4),
      rutin (7), tiliroside (14) and kaempferol (16) were quantified as others were in
      lesser amount. Syringic acid and quercetin were found in trace amount whereas
      chlorogenic acid was absent in the ethanol extract of roots of P. atrosanguinea.
      Total polyphenolic and flavonoid contents were determined to be 21.75 mg of
      gallic acid equivalent and 8.57 mg of quercetin equivalent per gram of dry plant
      material, respectively. Antioxidant activity of extract was assessed using three
      assays; 2,2'-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric reducing antioxidant
      power (FRAP). The IC50 values; 35.75 MUg/ml and 30.35 MUg/ml by DPPH and ABTS
      assays for ethanolic extract showed excellent free radical scavenging potential
      of its root part. The ferric reducing ability (FRAP) value, 26.67 mg of ascorbic
      acid per gram also indicated its higher antioxidant potential.

PMID- 30228434
TI  - Effect of sweeteners on anthocyanin stability and colour properties of sour
      cherry and strawberry nectars during storage.
AB  - Effects of various sweeteners (sucrose, maltose syrup and honey) on individual
      anthocyanins, colour and turbidity in sour cherry (SCN) and strawberry nectars
      (SN) were investigated during 168 and 42 days of storage at 20  degrees C,
      respectively. In SCN, major anthocyanin was cyanidin-3-glucosylrutinoside (cyd-3
      glu-rut), followed by cyanidin-3-rutinoside (cyd-3-rut), cyanidin-3-glucoside
      (cyd-3-glu) and cyanidin-3-sophoroside (cyd-3-soph). Maltose syrup increased
      stabilities of cyd-3-glu-rut (8%) and cyd-3-rut (4%), while honey reduced
      stabilities of all anthocyanins in SCN. Due to higher anthocyanin stability,
      maltose syrup for SCN was recommended. In SN, the major anthocyanin was
      pelargonidin-3-glucoside (pg-3-glu), followed by pelargonidin-3-rutinoside (pg-3
      rut) and cyd-3-glu. Stabilities of anthocyanins (46-51%) and colour density (6
      7%) in SN sweetened with honey were higher than that sweetened with sucrose and
      maltose syrup. Considering maximum wavelength (lambdamax), absorbance value at
      lambdamax (Amax), polymeric colour and colour density values together,
      copigmentation of anthocyanins occurred in SN sweetened with honey. This study is
      the first study showing copigmentation of anthocyanins with honey.

PMID- 30228435
TI  - Effect of adsorbent and acidulants on enzymatic browning of sugarcane juice.
AB  - Enzymatic browning is a major factor affecting the quality of sugarcane juice,
      mainly due to the activities of polyphenol oxidase (PPO) and peroxidase (POD).
      Effect of bentonite (0-1%, w/v) on the activities of these enzymes, when employed
      alone and also in combination with acidulants, was determined. Bentonite alone
      could reduce the activities of PPO and POD enzymes to 160 and 24.2 u/mL,
      respectively. The PPO and POD activity was completely inhibited below pH 4.1 when
      ascorbic acid was used alone or in combination with bentonite. However, PPO and
      POD activity was inhibited to 60 and 51 u/mL, respectively, at pH 3.7 when citric
      acid was used individually and to 112 and 15.36 u/mL, respectively, when employed
      along with bentonite. In addition, color changes at 4 and 10  degrees C were
      measured during the storage of sugarcane juice.

PMID- 30228437
TI  - 1 Picture = 1,000 Words.

PMID- 30228436
TI  - Application of FT-NIR spectroscopy for simultaneous estimation of taste quality
      and taste-related compounds content of black tea.
AB  - Fourier transform near-infrared spectroscopy (FT-NIR) coupled to chemometric
      algorithms such as back propagation (BP)-AdaBoost and synergy interval partial
      least square (Si-PLS) were deployed for the rapid prediction taste quality and
      taste-related components in black tea. Eight main taste-related components were
      determined via chemical analysis and Pearson correlations. The achieved chemical
      results of the eight taste-related components in black tea infusion were
      predicted based on 160 tea samples obtained from different countries. Prediction
      results revealed BP-AdaBoost models gave superior predictions, with all the
      correlation coefficients of the prediction set (Rp) > 0.76, and the root mean
      square error values of the prediction set (RMSEP) < 1.7% compared with Si-PLS
      models (0.71 <= Rp <= 0.94, 0.08% <= RMSEP <= 1.73%). This implies that FT-NIR
      combined to BP-AdaBoostis capable of being deployed for the rapid evaluation of
      black tea taste quality and taste-related components content simultaneously.

PMID- 30228439
TI  - Contributors to the MPHP 2015 Fund Raising Campaign.

PMID- 30228438
TI  - Web-Based Cognitive Behavioral Therapy Intervention for the Prevention of
      Suicidal Ideation in Medical Interns: A Randomized Clinical Trial.
AB  - Importance: In the United States, approximately 1 physician dies by suicide every
      day. Training physicians are at particularly high risk, with suicidal ideation
      increasing more than 4-fold during the first 3 months of internship year. Despite
      this increase, to our knowledge, very few efforts have been made to prevent the
      escalation of suicidal thoughts among training physicians. Objective: To assess
      the effectiveness of a web-based cognitive behavioral therapy (wCBT) program
      delivered prior to the start of internship year in the prevention of suicidal
      ideation in medical interns. Design Setting and Participants: A randomized
      clinical trial conducted at 2 university hospitals with 199 interns from multiple
      specialties during academic years 2009-2010 or 2011-2012. The current study was
      conducted from May 2009 to June 2010 and May 2011 to June 2012, and data were
      analyzed using intent-to-treat principles, including last observation carried
      forward. Interventions: Interns were randomly assigned to 2 study groups (wCBT
      and attention-control group [ACG]), and completed study activities lasting 30
      minutes each week for 4 weeks prior to starting internship year. Participants
      assigned to wCBT completed online CBT modules and those assigned to ACG received
      emails with general information about depression, suicidal thinking, and local
      mental health professionals. Main Outcomes and Measures: The Patient Health
      Questionnaire-9 was used to assess suicidal ideation (ie, "thoughts that you
      would be better off dead or hurting yourself in some way") prior to the start of
      intern year and at 3-month intervals throughout the year. Results: A total of
      62.2% of interns (199 of 320) agreed to take part in the study; 100 were assigned
      to the wCBT group and 99 to the ACG. During at least 1 point over the course of
      internship year, 12% of interns (12 of 100) assigned to wCBT endorsed suicidal
      ideation compared with 21.2% of interns (21 of 99) assigned to ACG. After
      adjusting for covariates identified a priori that have previously shown to
      increase the risk for suicidal ideation, interns assigned to wCBT were less
      likely to endorse suicidal ideation during internship year (relative risk, 0.40;
      95% CI, 0.17-0.91; P = .03) compared with those assigned to ACG. Conclusions and
      Relevance: This study demonstrates that a free, easily accessible, brief wCBT
      program is associated with reduced likelihood of suicidal ideation among medical
      interns. Prevention programs with these characteristics could be easily
      disseminated to medical training programs across the country. Trial Registration:
      anzctr.org.au Identifier: ACTRN12610000628044.

PMID- 30228441
TI  - MSMA Members in the News.

PMID- 30228440
TI  - Beware: Tax Identity Theft Scam Targets Physicians Again.

PMID- 30228443
TI  - 158thAnnual Convention, March 18-20, 2016 | St. Louis Renaissance Airport Hotel,
      www.msma.org/annual-convention.

PMID- 30228442
TI  - 158th Annual Convention, March 18-20, 2016, St. Louis Renaissance Airport Hotel,
      www.msma.org/annual-convention.

PMID- 30228444
TI  - 1 Picture = 1,000 Words.

PMID- 30228445
TI  - Beware: Tax-Related Identity Thefts Return.

PMID- 30228446
TI  - MSMA Members in the News.

PMID- 30228447
TI  - Kansas City Medical Society: Leadership, Innovation, Advocacy.

PMID- 30228448
TI  - MSMA Members in the News.

PMID- 30228449
TI  - Meet MSMA's 2016-2017 President.

PMID- 30228450
TI  - Jana Wolfe to Lead Medical Alliance.

PMID- 30228452
TI  - Recipients of the 50-Year Physician Pin.

PMID- 30228451
TI  - Let MSMA Take Care of the Big Stuff.

PMID- 30228453
TI  - House of Delegates Votes on Resolutions.

PMID- 30228455
TI  - Sponsors & Exhibit Partners.

PMID- 30228454
TI  - Awards: Arthur Gale Freedom of Expression.

PMID- 30228457
TI  - Reports of the Delegate Handbook: 2014-2015.

PMID- 30228456
TI  - Summary of Council Actions: 2015-2016.

PMID- 30228458
TI  - MSMA Elects Leadership.

PMID- 30228459
TI  - 2016 Annual Convention Attendance.

PMID- 30228460
TI  - Drug Company Compensated Physicians Role in Causing America's Deadly Opioid
      Epidemic: When Will We Learn?

PMID- 30228461
TI  - Kansas City Center for Practical Bioethics at Epicenter of Congressional Concerns
      about Conflicts of Interest with Pain Pill Industry.

PMID- 30228462
TI  - Rising Mortality from Substance Abuse Among Middle-Aged White Americans.

PMID- 30228463
TI  - Part I: Burnout Basics - Symptoms, Effects, Prevalence and the Five Main Causes.

PMID- 30228464
TI  - Heartland Virus: A New Virus Discovered in Missouri.

PMID- 30228466
TI  - War and Trauma: A History of Military Medicine.

PMID- 30228465
TI  - Successfully Incorporating Trainees in Medical Missions.

PMID- 30228467
TI  - Secure Disposal of Medical Practice Records.

PMID- 30228469
TI  - AMA Presidents from Missouri.

PMID- 30228468
TI  - AMA Chooses Missouri Physician as its Next President Elect!

PMID- 30228470
TI  - Problems with the 2015 Dietary Guidelines for Americans: A Rebuttal.

PMID- 30228471
TI  - Problems with the 2015 Dietary Guidelines for Americans: A Response to a
      Rebuttal.

PMID- 30228472
TI  - Medical Errors, Hysteria, and Death.

PMID- 30228473
TI  - Dietary Guidelines Head North.

PMID- 30228474
TI  - Over-Prescribed Medications/Under-Appreciated Risks.

PMID- 30228475
TI  - Member-Driven Goals Shape Cape Girardeau County Area Medical Society.

PMID- 30228476
TI  - MSMA Members in the News.

PMID- 30228477
TI  - UMKC Community and Family Medicine: A Heritage of Service Since 1851.

PMID- 30228478
TI  - The "Magic Triangle" Foundation to Effective Use of Information Technology in the
      Exam Room.
AB  - The computer has become an integral part of the exam room and plays an important
      role in provider-patient interaction. The special arrangement of the provider
      patient and computer as well as the provider's computer skills and hardware
      knowledge play a pivotal role in patient satisfaction, engagement and
      productivity. Patient satisfaction and engagement play an ever increasing role as
      medicine migrates to value-based reimbursement. How a physician uses the computer
      and interacts with patients in the exam room can encourage or discourage
      participation. Many physicians practice in rooms ill designed for optimal
      computer use. Learning how to adapt and incorporate the computer is a key patient
      interaction skill required of all clinicians. This paper discusses the research
      supporting this activity and describes how we are attempting to teach this to
      resident physicians in our practice.

PMID- 30228479
TI  - Clinical Competency Committee: Tools for Developing Tomorrow's Physician Leaders.

PMID- 30228480
TI  - A Triad of Dermatologic Dilemmas.
AB  - The U.S. health care system relies on primary care physicians to provide the
      majority of the dermatologic care-dermatologists see an estimated 30-40% of
      patients with dermatologic issues.1 Issues related to skin and mucous membrane
      conditions account for an estimated 8% of all visits to Family Physicians.2 Thus
      the primary care physician must be prepared to assess patients' with conditions
      benign or malignant, cosmetic or grave, irritants or harbingers of systemic
      illness, pathological or normal variant. In this article, three commonly seen and
      difficult to treat conditions will be reviewed.

PMID- 30228481
TI  - Primary Care Physician Supply for Missouri.
AB  - Primary Care Supply is not at a level to support needs for the U.S. public now or
      in the future. Missouri is deteriorating to an extreme shortage of primary care
      clinicians. With a present supply that is stagnant and not meeting patient needs,
      new opportunities to select and educate the next generation of physicians will be
      necessary to meet the predicted health care needs for our citizens. Examining the
      pipeline, process of medical education, practice transformation, and payment
      reform are important for the future.1 We should encourage our training
      institutions to provide resources for increasing the types of physicians we need
      for the next generation. Local and national leadership will need to heed the
      advice of forecasts and provide new methods and solutions for the needs of
      society. Academic institutions should be held to achieving a true output of
      physicians for the needs of society.

PMID- 30228482
TI  - What is a Patient-Centered Medical Home?
AB  - The concept of Patient-Centered Medical Home (PCMH) originated with the specialty
      of pediatrics to provide care to children with complex illness. Similar concepts
      were uncovered when researchers looked at high quality yet low cost health
      systems. PCMH concepts have been adopted by primary care professional
      organizations and are being supported by multiple other organizations. The
      implementation of PCMH practices by individual physician groups is accelerating
      with new payment models and other key drivers.

PMID- 30228483
TI  - To Supplement or Not.

PMID- 30228484
TI  - Emergency Medicine Interest Group Procedural Simulation Conference: An Experience
      for Multiple Learner Levels.
AB  - Prior research has identified knowledge gaps between the verbalization of
      procedures and performance in simulations. Against this background, we designed a
      procedural simulation conference to enhance our students' procedural skills
      development using instruction and deliberate practice. The conference had six
      procedure stations, each focusing on specific learning objectives. Sixty medical
      students and 20 instructors from University of Missouri-Kansas City's Emergency
      Medicine Interest Group participated. A majority rated the conference as helpful
      in enhancing students' procedural skills.

PMID- 30228485
TI  - Food Allergy Care: "It Takes a Team".
AB  - In 2011, the Division of Allergy/Immunology at Children's Mercy published a
      themed mini-series1 including an article on food allergies that recommended
      allergen avoidance and prevention/treatment of anaphylaxis as the key pillars of
      management.2 Since then, the escalating food allergy "epidemic" has stimulated
      diagnostic and therapeutic advances, as well as coordinated multidisciplinary
      approaches to treat nutritional imbalances and psychosocial issues. We aim to
      highlight the team approach to food allergy care in this article.

PMID- 30228486
TI  - Perioperative Evaluation and Optimization of Patients at Risk of Cardiac
      Complications for Non-Cardiac Surgery.
AB  - Major adverse cardiac events (MACE) are some of the most common complications
      occurring in the perioperative period. Even though traditionally more focus has
      been on the patient with ischemic disease other cardiac conditions pose a greater
      risk. The risk is related to both patient-specific and surgical factors. Patients
      with significant cardiac disease undergoing vascular or major surgery may have up
      to a 10% risk of major morbidity and mortality. Identifying modifiable risks and
      intervening pre-, intra- and postoperatively can improve outcomes.

PMID- 30228488
TI  - MMPAC.

PMID- 30228487
TI  - Obama Evaluates Obama Care Positively Some Analysts Disagree With His
      Conclusions.

PMID- 30228489
TI  - Physicians Running for Office.

PMID- 30228490
TI  - Part II: Prevent Physician Burnout: 8 Ways to Lower Practice Stress and Get Home
      Sooner.

PMID- 30228491
TI  - War and Trauma: A History of Military Medicine - Part II.

PMID- 30228492
TI  - E-Cigarettes: Safer Than Tobacco?

PMID- 30228493
TI  - MSMA Members in the News.

PMID- 30228494
TI  - Distinguished Editorial Service Recognition.

PMID- 30228495
TI  - Someday I'll Complete My Bucket List.

PMID- 30228497
TI  - Sixteen-Year-Old Diabetic High School Student Conducts & Presents National
      Research.

PMID- 30228496
TI  - The Burden and Benefits of Teenage Life with Type 1 Diabetes.

PMID- 30228498
TI  - Reducing the Burden of Diabetes Mellitus in the State of Missouri: A Call to
      Action.

PMID- 30228499
TI  - Missouri Medicine Annual Statement of Ownership, Management & Circulation.

PMID- 30228500
TI  - Diabetes Update 2016: What Bartleby the Scrivener Can Teach Us About Diabetes
      Care.

PMID- 30228501
TI  - New Pharmacologic Agents for Diabetes Treatment.
AB  - Therapeutic options for diabetes management have expanded dramatically in the
      last five years. While there continues to be consensus that lifestyle
      modification aimed at 5-7% weight loss and metformin are the appropriate first
      line therapies for type 2 diabetes, there are many options for intensification of
      diabetes management. The American Diabetes Association (ADA) and the American
      Association of Clinical Endocrinologists (AACE) have released recent guidelines
      that prioritize use of the newer classes of medications.1,2 There are a number of
      considerations in selecting medications, including risk of hypoglycemia, effect
      on body weight, adverse event profile, renal function, and cost/insurance
      coverage. The objective of this article is to discuss mechanism, efficacy, and
      safety for each new class of medications. We conclude with a quick reference for
      the use of these medications in primary and specialty care, based on their
      various attributes and patient and provider preferences.

PMID- 30228502
TI  - Improving Diabetes Care with Technology and Information Management.
AB  - Patients and physicians in the 21st century require new tools to manage the
      growing burden of chronic illness. For providers responsible for the care of
      diabetic patients, developments in information management, real-time health
      education and feedback, and new approaches to self-monitoring and insulin
      delivery hold great promise to improve the quality and safety of diabetes care.
      This article will briefly highlight some of the major developments in the field,
      and the ways these technologies can be integrated into a typical practice.

PMID- 30228503
TI  - Modern Strategies to Save Sight in Diabetes.
AB  - Owing to the global epidemic of obesity, the incidence of diabetes and its
      complications are rapidly increasing around the world. Yet, visual impairment
      caused by diabetic retinopathy is paradoxically on the decline. This improvement
      is due to better understanding of etiologic mechanisms, increased screening, and
      advent of newer therapies. Here, we discuss salient developments in the
      comprehension of the root causes of diabetic retinopathy and the molecular
      mechanisms underlying current treatment approaches.

PMID- 30228504
TI  - Glucocorticoids and Diabetes.
AB  - Glucocorticoids (GCs), stress hormones produced by the adrenal gland, are
      involved in many pathways in physiology and metabolism including glucose
      homeostasis and inflammation. Excess GC signaling results in Cushing's syndrome
      and possibly metabolic syndrome. Diabetes, central adiposity, and hyperlipidemia
      are components of both syndromes. Here, we discuss the mechanisms of GC action,
      clinical syndromes of GC excess, modulation of glucose homeostasis by GCs, and
      future treatments for diabetes based on GC signaling.

PMID- 30228506
TI  - Diabetic Kidney Disease.
AB  - Diabetic kidney disease (DKD) continues to be a chronic and devastating
      complication of diabetes. Despite improvements in glycemic control and lower
      blood pressure targets, the incidence of DKD has not declined substantially.
      Standards of care for persons with diabetes include screening for kidney
      complications and close follow-up. Preventive measures continue to rely on
      glucose and blood pressure control. However, additional measures to slow the
      progression of kidney damage are under investigation.

PMID- 30228505
TI  - Cystic Fibrosis Related Diabetes: a Unique Challenge in Diabetes Care.
AB  - Cystic Fibrosis (CF) is a common autosomal recessive disease that affects
      multiple organs due to a defect in the gene encoding the cystic fibrosis
      transmembrane conductance regulator (CFTR). This transporter is present in
      various organs and tissues, including the airway epithelium, sinuses, pancreas,
      intestine, biliary tree, the vas deferens, and the sweat ducts, making CF a multi
      system disease1. As CF patients are living longer, pancreatic function declines
      and diabetes emerges, further complicating the nutritional status and care of
      these patients.

PMID- 30228509
TI  - Warning: Medicare May Be Bad for Your Heart.

PMID- 30228507
TI  - Death by Carbs: Added Sugars and Refined Carbohydrates Cause Diabetes and
      Cardiovascular Disease in Asian Indians.
AB  - By the year 2030, India will supplant China as the world's most populous nation.
      Rapid urbanization and an increasingly Westernized diet and lifestyle, in a
      population with genetic predisposition to insulin resistance is fueling a rising
      epidemic of non-communicable diseases in India. A diet that is high in processed
      foods, added sugars and other refined carbohydrates is a principle factor driving
      the growing epidemics of type 2 diabetes (T2D), hypertension (HTN), and
      cardiovascular (CV) disease (CVD). Immediate postprandial spikes in the blood
      levels of glucose and triglycerides cause immediate parallel rises in oxidative
      stress, inflammation, and endothelial dysfunction; eventually leading to T2D, and
      CVD. Furthermore the Asian Indian population is particularly susceptible to
      exaggerated rises in postprandial glucose and triglycerides because they are
      genetically predisposed to metabolic syndrome (MetSyn), insulin resistance, and
      T2D. A diet restricting the consumption of refined carbohydrates and limiting
      added sugars to not more than 5 grams/day should be adopted by Asian Indians to
      reduce risk of T2D, HTN, coronary disease, and stroke.

PMID- 30228508
TI  - Calcific Aortic Stenosis: New Approaches to an Old Disease.
AB  - Calcific aortic valve disease affects up to 25% of all adults over 65 years of
      age, with most only having focal valve thickening called aortic sclerosis.
      However, up to 5% of older adults have significant aortic stenosis (AS) with some
      degree of obstruction to left ventricular outflow. 1,3,4,5 Once even mild valve
      obstruction is present, hemodynamic progression is common, leading to severe
      symptomatic or asymptomatic AS that eventually requires aortic valve replacement
      in some fashion. 6,7 With our aging population, an increasing number of patients
      with AS will be presenting for evaluation and care.

PMID- 30228510
TI  - Building a Targeted Asthma Education and Management Program.
AB  - For individuals with asthma, self-management at home can be complex and
      overwhelming. The National Asthma Guidelines recommend education, ongoing
      assessment of control, and identification of those at high risk, as integral
      elements of improving outcomes for these individuals. Children's Mercy
      implemented standardized, patient-centered asthma education interventions along
      with institution of asthma control assessment tools and targeted management of
      high risk asthmatics. Many of these tools are applicable for use in primary care
      ambulatory practices.

PMID- 30228511
TI  - Bridging the Radiology-Pediatrics Interaction Gap by Incorporating a PGY4
      Radiology Resident into the General Pediatrics Team.
AB  - To bridge the gap between clinicians and radiologists, radiology residents
      rounded with inpatient pediatric medicine teams to present and interpret daily
      imaging studies, as well as assist with decisions and indications for radiologic
      exams. Surveys were sent to team members who rotated with radiology residents,
      and the consensus strongly favored having radiology residents on future
      rotations. Team members responded that they benefitted from a better
      understanding of radiology exams, their indications and limitations.

PMID- 30228513
TI  - Belonging to MSMA and Advocating for Medicine: Why It Matters for All Physicians.

PMID- 30228512
TI  - When Did You Last Speak A Radiologist or Visit the Radiology Department?

PMID- 30228514
TI  - Get to Know Your Physician Legislators.

PMID- 30228515
TI  - Forecast for 99th General Assembly.

PMID- 30228516
TI  - Advocating for What Is Important to Medicine.

PMID- 30228517
TI  - Physician Advocacy: The AMA Interim Meeting 2016.

PMID- 30228518
TI  - Fifty Years of Trauma.

PMID- 30228519
TI  - Should Nurse Practitioners Be Allowed to Practice Independently?

PMID- 30228520
TI  - Physicians Present Opposing Views of Hospitalists.

PMID- 30228521
TI  - Physician-Owned Surgical Hospitals Outperform Other Hospitals in Medicare Value
      Based Purchasing Program.

PMID- 30228522
TI  - Inspector General: Medicare spends hundreds of millions on medically unnecessary
      chiropractic services.

PMID- 30228524
TI  - A Brave New Weed.

PMID- 30228523
TI  - How Obama's FDA Keeps Generic Drugs Off the Market.

PMID- 30228525
TI  - Measuring and Mattering.

PMID- 30228526
TI  - The Joint Commission Deserves Some Blame for the Opioid Crisis.

PMID- 30228527
TI  - Prevent Physician Burnout: 4 Work-Life Balance Tools.

PMID- 30228528
TI  - Tax Identity Theft Scam Targets Physicians Again.

PMID- 30228529
TI  - Medical Patents and How New Instruments or Medications Might Be Patented.

PMID- 30228530
TI  - Missouri's First New Medical School in Nearly 50 Years Comes to Joplin.

PMID- 30228532
TI  - Burnout, Suicide Impact Medicine.

PMID- 30228531
TI  - MSMA Members in the News.

PMID- 30228533
TI  - 159th Annual Convention March 31-April 2, 2017 | Sheraton Kansas City Hotel at
      Crown Center | Kansas City, MO www.msma.org/annual-convention.

PMID- 30228534
TI  - General Sessions & Events.

PMID- 30228536
TI  - Low Dose CT for Lung Cancer Screening Could Provide Substantial Benefit.

PMID- 30228535
TI  - The Evolution of a Regional Lung Cancer Screening Program.

PMID- 30228537
TI  - Boys at Risk: Fatal Accidental Fentanyl Ingestions in Children: Analysis of Cases
      Reported to the FDA 2004-2013.
AB  - We analyze 25 accidental childhood fentanyl exposures reported to FDA, 2004-2013.
      These exposures had a case-fatality rate = 48%; male:female ratio = 7.3; 76% were
      within the 2-4 age range. The ability of fentanyl to kill children so quickly is
      explained by fentanyl's ability to suppress respiration-as quantified by the
      antinociceptive potency per milligram, fentanyl far and away leads all narcotics.
      FDA recommends for fentanyl disposal: flush all forms of fentanyl down the
      toilet.

PMID- 30228539
TI  - Understanding Patient Perceptions of Hypertension for Optimal Management in a
      Student-Run Free Clinic.
AB  - The burden of hypertension (HTN) is disproportionately high among adults with low
      socio-economic status. Our objective was to examine the knowledge, attitudes and
      barriers related to HTN among this cohort. Using a mixed-methods approach, we
      interviewed twenty adults at a student-run safety-net health clinic. Most
      patients recognized HTN-related risks, but themes of denial, financial burden and
      misinformation emerged when addressing treatment adherence. Our findings
      highlight an urgent need to address patient-centric approaches in HTN management.

PMID- 30228540
TI  - The Science of Near-Death Experiences A Book by Missouri Medicine Authors Is Now
      in Print and World-Standard.

PMID- 30228541
TI  - Should Physicians Ever Retire?

PMID- 30228538
TI  - Acute Ischemic Stroke: Current Status and Future Directions.
AB  - The evolving knowledge on stroke in conjunction with advances in the field of
      imaging, treatment approaches using recombinant tissue plasminogen activator
      (rtPA) or thrombectomy devices in recanalization, and efficient emergency stroke
      workflow processes have opened new frontiers in managing patients with an acute
      ischemic stroke. These frontiers have been reformed and overcome in overcoming
      the decades-long watch and wait approach towards patients with ischemic stroke.
      In this article, we focus on the current strategies for managing ischemic stroke
      and conclude by providing a brief overview of anticipating developments that can
      transform future stroke treatments.

PMID- 30228542
TI  - Adam Hammer, MD: The St. Louis Physician Who Made the First Ever Diagnosis of
      Coronary Thrombosis and Acute Myocardial Infarction in a Living Patient.

PMID- 30228543
TI  - The Opioid Epidemic: It's Time to Place Blame Where It Belongs.

PMID- 30228544
TI  - Physician-Driven Innovation and Determination Leads the War on Drunk Driving in
      One Missouri Community.

PMID- 30228545
TI  - Drunk Driving and Vehicle Forfeiture: A Good Effort Cut Short.

PMID- 30228547
TI  - Barriers to Mental Illness and Substance Abuse Treatment Among Physicians and the
      Impact on Patient Care.

PMID- 30228546
TI  - An Rx for DWI.

PMID- 30228548
TI  - The Privilege to Meet MSMA Members.

PMID- 30228549
TI  - Put Me Back In Coach! Concussion and Return to Play.

PMID- 30228551
TI  - MSMA Members in the News.

PMID- 30228550
TI  - Praise for "I Stuffed Their Mouths with Gold".

PMID- 30228552
TI  - Kudos to Editor John Hagan, III, MD.

PMID- 30228553
TI  - The Importance of Geriatric Syndromes.

PMID- 30228554
TI  - The Rapid Geriatric Assessment: A Quick Screen for Geriatric Syndromes.

PMID- 30228555
TI  - Physical Activity in Older Persons.
AB  - Physical activity in older adults has been shown to improve physical, cognitive
      and functional status and to reduce risk of frailty. Guidelines recommend at
      least 150 minutes of moderate-intensity aerobic physical activity each week as
      well as strength activities. There is little evidence of adverse events or harm
      with regular physical activity in older adults. Group-based and center-based
      models may help maximize short-term benefits, but creating home-based activities
      can improve the long-term compliance of a physical activity program.

PMID- 30228556
TI  - Palliative Care: An Update.
AB  - Population across the globe is not only aging but also suffering from serious
      illness. This is critically important in providing patient-centered end of life
      (EOL) care. The following article intends to describe what are the principles of
      palliative care (PC), how PC assists in the care of patients with cancer and
      serious illness across settings, current delivery of EOL care, and the future of
      PC with novel models of delivery.

PMID- 30228557
TI  - Non-Pharmacologic Interventions for Persons with Dementia.
AB  - Affecting over 100,000 older Missourians, cognitive impairment is of concern for
      all health care providers. With no available pharmacologic treatments to
      eradicate/diminish symptoms, professionals and families need non-pharmacologic
      behavioral interventions to enhance individuals' quality-of-life and decrease the
      number and intensity of dementia-related behavioral symptoms. This paper provides
      an overview of available evidence-based non-pharmacologic interventions and
      strategies that can be delivered in both the community and facility setting,
      including reminiscence, validation, and cognitive stimulation therapies.

PMID- 30228558
TI  - Obstructive Sleep Apnea Diagnosis and Management.
AB  - The diagnosis and treatment of obstructive sleep apnea is discussed in the
      context of recent diagnostic and therapeutic advances.

PMID- 30228559
TI  - Looking for PANDAS in Missouri.
AB  - This review seeks to educate clinicians and advocate for patients having acute
      onset pediatric autoimmune encephalopathy. Primary care providers caring for
      children are not fully aware of the debilitating illness that changes the life of
      a child and a family overnight. Our goal is to heighten awareness of a) the
      initial diagnosis, b) treatment and c) information about referral of affected
      children by health professionals in Missouri and surrounding states.

PMID- 30228560
TI  - Liquid Nitrogen Cryotherapy Treatment of Herpes Simplex Epithelial Keratitis.
AB  - A retrospective case series was performed in a university setting for all
      patients with herpes simplex epithelial keratitis who underwent liquid nitrogen
      cryotherapy from 2012-2015. Outcome measure was clinical evidence of resolution
      of epithelial keratitis in the cornea with re-epithelialization. All cases of
      epithelial keratitis showed partial and complete resolution at day 1 and week 1
      respectively. Liquid nitrogen cryotherapy is a safe and effective treatment for
      herpes epithelial keratitis comparable to other published studies.

PMID- 30228561
TI  - Son's Death to Opioid Abuse Was "Completely Unnecessary".

PMID- 30228562
TI  - The ER Doctor's Role in Combating the Opioid Epidemic.

PMID- 30228563
TI  - Call Coverage Rates: What's Driving That Number?

PMID- 30228565
TI  - MSMA Introduces: Medical Student Mentor Program.

PMID- 30228564
TI  - Thankful to be a Missourian.

PMID- 30228566
TI  - Pay for Genomics.

PMID- 30228568
TI  - Genomic Database Grows.

PMID- 30228569
TI  - MSMA Members in the News.

PMID- 30228570
TI  - A National Leader in Women's Reproductive Health.

PMID- 30228571
TI  - A History of Developments to Improve in vitro Fertilization.
AB  - Methods of in vitro fertilization (IVF) have advanced dramatically since the
      first IVF baby was born in 1978. Originally yielding single-digit success rates,
      IVF is now successful in nearly 50% of cases in which the woman is younger than
      35 years. Here, we describe the improvements in laboratory techniques and
      advances in our abilities to manipulate reproductive physiology that have
      facilitated this improvement. Additionally, we describe efforts to ensure safety
      standards in this competitive field.

PMID- 30228572
TI  - Identifying the Best Way to Manage Labor.
AB  - The second stage of labor, defined as the interval from complete cervical
      dilation through delivery of the fetus, is the most physiologically demanding
      period of labor for both the mother and the fetus. Additionally, prolongation of
      this stage can lead to operative deliveries, which are associated with increased
      risks of adverse neonatal and maternal outcomes. However, the optimal technique
      for managing maternal pushing during this stage, immediate or delayed pushing, is
      unknown. Washington University School of Medicine is addressing this question by
      conducting a large, multi-site, randomized controlled trial that will assess both
      maternal and neonatal outcomes. Completion is expected by 2018.

PMID- 30228573
TI  - Meeting the Contraceptive Needs of a Community: Increasing Access to Long-Acting
      Reversible Contraception.
AB  - To control their reproductive lives, women must have access to all contraceptive
      methods including the most effective reversible methods, intrauterine devices,
      and implants. The Contraceptive CHOICE Project, a study of 9,256 women in St.
      Louis, showed that when barriers to contraception are removed, many women choose
      intrauterine devices and implants, substantially reducing rates of unintended
      pregnancy and abortion. This article discusses strategies we learned from the
      CHOICE Project to improve uptake of the most effective contraceptive methods.

PMID- 30228574
TI  - Zika Virus Takes a Transplacental Route to Infect Fetuses: Insights from an
      Animal Model.
AB  - Zika virus (ZIKV) has been linked to intrauterine growth restriction (IUGR),
      spontaneous miscarriage, and microcephaly in infants of women infected during
      pregnancy. To determine how ZIKV affects the fetus, we infected pregnant mice
      subcutaneously (mimicking a mosquito bite) with ZIKV. Multiple techniques
      revealed that ZIKV replicated within placental trophoblasts, fetal endothelial
      cells, and the fetal neocortex. We also noted severe placental defects, IUGR, and
      fetal death. Thus, our mouse model recapitulated ZIKV infection in human
      pregnancy and demonstrated that ZIKV can be transmitted from mother to fetus via
      the placenta.

PMID- 30228575
TI  - Apical Vaginal Support: The Often Forgotten Piece of the Puzzle.
AB  - Pelvic organ prolapse is common among women who have delivered vaginally or had a
      hysterectomy. In a total hysterectomy, the apical vaginal support is transected.
      Although evidence supports re-establishment of apical support, our research
      showed that this rarely occurs in hysterectomies. To address our lack of
      definitions of "significant" apical support loss and recommendations to guide
      surgeons as to when they should perform an apical support procedure, we analyzed
      patient data and found that a simple assessment of the genital hiatus can
      effectively screen for significant apical support loss. Our work will hopefully
      highlight the importance of apical support loss and current deficits in research
      and clinical guidelines.

PMID- 30228576
TI  - Uterine Morcellation: Fact and Fiction Surrounding the Recent Controversy.
AB  - Minimally invasive surgery is commonly used for hysterectomies because of its
      many benefits over open surgery. Although small uteri can be removed whole in
      this approach, larger specimens must be morcellated. Power morcellation has come
      under scrutiny recently because of concerns that it can disseminate occult
      uterine sarcoma, other undiagnosed malignancies, and benign tissue. To limit
      uterine tissue dissemination, morcellation can be contained within a bag. In
      addition, a careful preoperative workup should be performed to minimize the risk
      of occult malignancy. New techniques that allow surgeons to offer more women a
      minimally invasive approach should be investigated and encouraged.

PMID- 30228577
TI  - Opioid Use Disorder and Pregnancy.
AB  - Over-prescription of opioid pain medications and increases in heroin use have
      contributed to the sharp rise in opioid-related hospitalizations and overdose
      deaths among young adults in the United States, including pregnant women. This
      has imposed substantial direct and indirect costs to our nation's health care
      system. Effective treatment with methadone and buprenorphine is available, but
      significant barriers to care may restrict access for many. Improved screening
      tools and expanded access to treatments for substance use disorders are keys to
      addressing the epidemic of opioid use disorder.

PMID- 30228578
TI  - Comparison of Family Medicine and General Internal Medicine on Diabetes
      Management.
AB  - : The majority of patients with type 2 diabetes are managed in primary care,
      either in family medicine (FM) or general internal medicine (GIM). Variances in
      training, beliefs and practice decisions between FM and GIM may result in
      differing approaches to diabetes management. This study found that differences do
      exist in the choice of treatment by FM vs GIM; however, these differences are
      driven by patient characteristics and does not result in glycemic control
      disparities. Background and Objectives: Approach to management of chronic health
      conditions differs between family medicine (FM) and general internal medicine
      (GIM). Differences might be due to beliefs, patient case mix, training, and/or
      experience. This study determined if FM and GIM diabetes management differences
      exist, and if so, resulted in better or worse glycemic control. Method:
      Electronic medical record data from 2008-2013 were used to identify 976 patients
      (287 FM and 689 GIM) with type 2 diabetes and prescriptions for metformin. GEE
      type regression models were computed to control for repeated measures and
      estimate the association between primary care specialty and glycemic control,
      defined as percent of patients with HgA1c<8.5 and average HgA1c. Covariates
      included demographics, comorbidities, smoking and health care utilization, and
      diabetes treatment. Results: Compared to FM patients, significantly more GIM
      patients received a non-metformin medication (35.9% vs 47.2%) and insulin (16.4%
      vs 23.8%). After adjusting for covariates, FM patients had significantly lower
      HgA1c values (B = -.47; 95% CI: -0.68, -0.27) and were less likely to have an
      HgA1c>8.5 (OR=0.55; 95%CI:0.40-0.77). FM vs GIM patients did not differ in degree
      of HgA1c improvement over time. Conclusions: FM patients vs GIM patients are less
      likely to receive a non-metformin and insulin medication. Differences in diabetes
      management likely correspond to degree of HgA1c control. Choice of treatment
      appears to reflect patient needs as both FM and GIM patients experienced equal
      improvement in HgA1c. Primary care specialty differences in beliefs and practices
      around diabetes management do not result in disparities in patient care.

PMID- 30228579
TI  - Chronic Lymphocytic Leukemia and the Side Effects of Therapy: 2017 Review.
AB  - In recent years, the choice of therapies for symptomatic Chronic Lymphocytic
      Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) have grown exponentially, with no
      single agreed upon standard first-line therapy. The choice of therapy is often
      dictated by goals of care, patient characteristics and tumor genetic
      abnormalities. The goal of this article is to familiarize the primary care
      provider with some of the most commonly used therapeutic modalities with
      attention to the side effect profile of these regimens.

PMID- 30228580
TI  - Meet MSMA's 2017-2018 President.

PMID- 30228582
TI  - State of the Association: Presidential Address.

PMID- 30228581
TI  - Marsha Conant to Lead Medical Alliance.

PMID- 30228583
TI  - Dwell on the Positive.

PMID- 30228584
TI  - Recipients of the 50-Year Physician Pin.

PMID- 30228585
TI  - House of Delegates Votes on Resolutions.

PMID- 30228586
TI  - Awards: Legislative.

PMID- 30228587
TI  - Sponsors & Exhibit Partners.

PMID- 30228588
TI  - MSMA Elects Leadership.

PMID- 30228590
TI  - Reports of the Delegate Handbook: 2016-2017.

PMID- 30228589
TI  - Summary of Council Actions: 2016-2017.

PMID- 30228591
TI  - Missouri State Medical Association Financial Statement.

PMID- 30228593
TI  - 2017 Annual Convention Attendance.

PMID- 30228592
TI  - Missouri Physicians Health Program Financial Statement.

PMID- 30228595
TI  - Should Missouri Have a Statewide Prescription Drug Monitoring Program?

PMID- 30228594
TI  - King Canute's Court.

PMID- 30228596
TI  - The Case for a PDMP in Missouri.

PMID- 30228597
TI  - Prescription Drug Monitoring Program: Useful Tool or Government Control?

PMID- 30228598
TI  - Close Examination of a ZYTO Electrodermal Screening System.
AB  - Electrodermal screening" ("EDS") devices are claimed to use galvanic skin
      responses to identify health problems and corrective actions. Thousands are being
      used to persuade people to buy dietary supplements, diet programs, and other
      offerings. This study, which involved self-testing with a leading EDS device 43
      times in 10 days, found that its assessments and recommendations were
      preposterous and potentially dangerous. The sale and clinical use of EDS devices
      should be banned.

PMID- 30228599
TI  - Membership Matters.

PMID- 30228600
TI  - Missouri Physician Installed as AMA President.

PMID- 30228601
TI  - A New AMA Policy - More Time Spent Outdoors May Reduce the Risk of Kids'
      Nearsightedness.

PMID- 30228602
TI  - Management of Missouri Snake Bites.

PMID- 30228603
TI  - Clinical Experience With Management of 20 Brown Recluse Spider Bites: An
      Effective Treatment Regimen.

PMID- 30228604
TI  - When's My Doctor Coming In?

PMID- 30228606
TI  - MSMA Members in the News.

PMID- 30228605
TI  - Dangers of Falling.

PMID- 30228607
TI  - UMKC Health Sciences District: An Innovative Enterprise to Advance Health and
      Health Care.

PMID- 30228608
TI  - Providing Musculoskeletal Care and Education in Kansas City.

PMID- 30228609
TI  - Adverse Effects of Smoking on Musculoskeletal Health.
AB  - Smoking remains a prevalent part of present day society, with over 42 million
      Americans who continue to use cigarettes. Smoking is strongly associated with a
      variety of conditions that result in increased morbidity and mortality. Research
      also indicates that smoking has an adverse effect on surgical outcomes. Its
      effect on the musculoskeletal system is evident and results in postoperative
      complications such as infection, nonunion, and malunion. These complications also
      come with a price, as there are severe economic implications of smoking. Patients
      who smoke may benefit from a period of perioperative cessation to help diminish
      some of these negative outcomes. It is the physician's duty to educate patients
      preoperatively about these outcomes and the potential benefit of smoking
      cessation.

PMID- 30228610
TI  - The Economic Impact of Orthopaedics in Missouri.
AB  - Orthopaedics contributes a significant benefit to the Missouri economy. Economic
      modeling and data quantified the direct and indirect impact within Missouri.
      Multipliers were applied to direct expenditures to calculate the indirect impact
      attributable to initial spending. Nearly $1.8 billion can be attributed to the
      output of orthopaedic related services. The related physical therapy industry
      increases this figure to nearly $2.3 billion. It is clear that orthopaedics
      benefits Missouri with both medical services and economic growth.

PMID- 30228611
TI  - New Paradigms in Post-Graduate Surgical Education.
AB  - With a growing focus on patient safety and trainee education, the Accreditation
      Council for Graduate Medical Education implemented changes including work hour
      restrictions, focused clinical competencies, and the Next Accreditation System
      (NAS). The NAS poses initial challenges on residencies with the implementation of
      surgical simulation programs and defining resident competency. It is the hope
      that innovative training methods will allow for improved advancement of knowledge
      and surgical skills given the current direction of post-graduate surgical
      training.

PMID- 30228612
TI  - FDA Device Regulation.

PMID- 30228613
TI  - Evaluating Soft-Tissue Lumps and Bumps.
AB  - Patients presenting with soft-tissue lumps and bumps are commonly encountered by
      both primary care physicians and orthopaedic surgeons. Though common, the initial
      evaluation and management of a soft-tissue mass can be challenging for many
      clinicians due to the considerable overlap in the presentation of benign and
      malignant tumors. Furthermore, a myriad of conditions, ranging from infection to
      trauma, can present with a soft-tissue mass. Subsequently, the correct diagnosis
      is often delayed or missed which may ultimately lead to inappropriate treatment.
      The propose of this article is to review the fundamental elements of a successful
      soft-tissue mass work-up and to provide the clinician with a systematic approach
      to the evaluation, diagnosis and management of the patient with a soft-tissue
      tumor.

PMID- 30228614
TI  - The Role of the Fracture Liaison Service in Osteoporosis Care.
AB  - Osteoporosis is a disease classified by the alteration of bony microarchitecture
      predisposing a person to fragility fractures. This costs the US $19 billion per
      year and is expected to rise as our population ages. Only 20% of patients with
      fragility fractures receive treatment for osteoporosis. A Fracture Liaison
      Service is a cost-effective way to follow patients and improve appropriate work
      up and management from multiple medical disciplines.

PMID- 30228615
TI  - Femoroacetabular Impingement Syndrome: A Cause of Hip Pain in Adolescents and
      Young Adults.
AB  - The primary objective of this review is further education of the general
      practitioner, or family medicine physician, on an important, but often missed,
      cause of hip pain in the adolescent and young adult population, femoroacetabular
      impingement (FAI) syndrome. We hope that further understanding of the etiology,
      examination, diagnosis, and treatment of FAI, will lead to more accurate
      diagnosis and timely referral to the Orthopedic hip specialist for definitive
      treatment and management. Thus, preventing the complications, or late sequelae,
      associated with the condition.

PMID- 30228617
TI  - Penetrating Ocular Trauma from a Bean Bag Gun: A Case Report and Review of Less
      Lethal Force and Their Consequences.
AB  - Although bean bag guns are considered a "less-lethal" form of law enforcement,
      these blunt projectiles have risk. The purpose of this study was to perform a
      literature review of morbidity and mortality associated with less-lethal
      munitions and present a case report of a bean bag injury leading to a traumatic
      globe evisceration and skull base fracture. Patients presenting with bean bag gun
      associated injuries warrant a high clinical suspicion for injury to deeper
      structures.

PMID- 30228616
TI  - Good Fats versus Bad Fats: A Comparison of Fatty Acids in the Promotion of
      Insulin Resistance, Inflammation, and Obesity.
AB  - Recently, debate has erupted in both the scientific community and throughout the
      lay public around whether a low-fat or low-carbohydrate diet is better for weight
      loss. In other words, is it better to cut fat or cut carbohydrate for weight
      loss. However, going beyond this debate (fat versus carbohydrate), are questions
      around whether certain fatty acids are worse for promoting insulin resistance,
      inflammation, and obesity. The overall evidence in the literature suggests that
      medium-chain saturated fats (such as lauric acid, found in coconut oil) and
      monounsaturated fat (oleic acid, found in olive oil) are less likely to promote
      insulin resistance, inflammation, and fat storage compared to long-chain
      saturated fatty acids (such as stearic acid found in large quantities in butter,
      but particularly palmitic acid found in palm oil) especially when consumed on top
      of a diet moderate in refined carbohydrates. Compared to long-chain saturated
      fats, lauric acid and oleic acid have an increased fatty acid oxidation rate, are
      more likely to be burned for energy and less likely to be stored in adipose
      tissue, and thus promote increased energy expenditure. Omega-6 polyunsaturated
      fatty acids (PUFAs), such as linoleic acid, as found in vegetable oils may
      contribute to obesity, whereas omega-3 PUFA may be protective. Importantly, both
      olive oil as part of a Mediterranean diet, and omega-3 from fish and fish oil
      have been proven to reduce risk of cardiovascular (CV) events.

PMID- 30228618
TI  - Sleep and Dementia.
AB  - Neurocognitive and sleep problems are common, underdiagnosed, and frequently co
      morbid. Sleep disruption, and fatigue, predict cognitive impairment. Cognitive
      impairment, in turn, can worsen sleep hygiene. In dementia patients, sleep
      disorders are common, and dementia medications affect sleep. Emerging insights on
      the brain's glymphatic system suggests that sleep may drive clearance of Abeta
      peptide to affect Alzheimer pathophysiology. Parkinsonian dementias are linked
      with REM behavior disorder, a highly treatable problem that predicts future
      conversion into dementia.

PMID- 30228619
TI  - Embedding a Medical Search Engine Within an Electronic Health Record.
AB  - This study investigates an information retrieval tool embedded in an electronic
      health record (EHR). 1-Search provides a single search for retrieving information
      from a variety of content sources. 1-Search's usefulness and impact were
      determined by measuring the extent of physicians' information needs, pre- and
      post-implementation user satisfaction, and the impact of 1-Search on clinical
      decision-making. Results support incorporation of 1-Search into the EHR, the
      continued use of 1-Search, and further development.

PMID- 30228620
TI  - Gallows-humor? Docs don't like the hang of it!: "Bad Medicine" Newspaper Beat
      Draws Rapid National Condemnation.

PMID- 30228621
TI  - Is Marijuana Use for Pain Driving Negative Societal Effects?

PMID- 30228622
TI  - Pro: The Case for a PDMP in Missouri.

PMID- 30228623
TI  - Con: Prescription Drug Monitoring Program: Useful Tool or Government Control?

PMID- 30228625
TI  - E-Cigarettes: Current Evidence and Policy.

PMID- 30228626
TI  - Concussion Care: Moving Beyond the Standard.

PMID- 30228624
TI  - A la recherche du temps perdu: Smoking and Genomic Imprinting.
AB  - Tobacco smoking is the largest cause of preventable mortality and morbidity in
      the United States. Many of the pathological consequences of smoking result from
      mutations, but gene expression can also be modulated by genomic imprinting
      mediated by DNA methylation-so-called "epigenetic" regulation. Since genomic
      imprints, unlike gene mutations, can be reversed, it is of great interest what
      smoking-related imprints mean for smoking-related pathologies in smokers and
      their children, and the potential for imprint-targeted diagnostics and
      therapeutics.

PMID- 30228627
TI  - Project Apache: Bringing Pediatric Care to an Arizona Reservation circa 1972.

PMID- 30228629
TI  - MSMA Members in the News.

PMID- 30228628
TI  - A Lifetime of Service.

PMID- 30228630
TI  - Double Drat - Diagnosis of Brown Recluse.

PMID- 30228631
TI  - Kansas City University: A Private University with a Very Public Mission.

PMID- 30228633
TI  - Innovations in Training the Next Generation of Physicians for Missouri and the
      Nation.

PMID- 30228632
TI  - System-Based Models of Care Influencing Population Health Outcomes.

PMID- 30228634
TI  - Addressing Rural Health Challenges Head On.
AB  - Providing health care to patients and families living in rural America presents
      significant challenges, but comes with unique rewards. The physician who chooses
      a rural life typically cares for an underserved and aging population, which is
      often less healthy and affluent than its urban and suburban counterparts. At the
      same time, rural clinicians feel deeply connected to their patients and their
      communities. Physicians cite strong doctor-patient relationships as a primary
      motivator to practice in a rural setting, in addition to lower cost of living and
      slower pace of life1. Those who choose primary care specialties also enjoy the
      challenge of caring for multiple, interrelated aspects of health for their
      patients and community. During Kansas City University of Medicine and
      Biosciences' (KCU) century-long history, we have offered our osteopathic medical
      students the opportunity to learn in rural areas during the third and fourth
      years. As our new, state-of-the-art medical school campus opens in Joplin,
      Missouri, we will build on our commitment to rural health by offering first- and
      second-year KCU-Joplin students training opportunities in rural settings, and
      expanding third- and fourth-year rural clinical rotations. The rich experience to
      learn rural medicine offers the potential to connect medical students, patients
      and community in new and exciting ways, building on the firm foundation of
      osteopathic medical training grounded in strong patient-centered primary care.

PMID- 30228635
TI  - Flagship Program Provides a Model for Early Clinical Exposure, Service to
      Community.

PMID- 30228636
TI  - How Kansas City University is Creating a National Model for Student Wellness.

PMID- 30228637
TI  - Training Medical Scientists of the Future.

PMID- 30228638
TI  - Advancing Health Services Teams: KCU Launches Only Clinical Psychology Program in
      the Two-State Region.

PMID- 30228639
TI  - Leveraging Partnerships and Collaboration to Advance Research: Kansas City
      Musculoskeletal Disease Consortium.

PMID- 30228640
TI  - Sleep and Parkinson Disease.
AB  - Sleep disorders are prevalent in Parkinson disease (PD), a disease with well
      recognized motor dysfunction. Sleep related problems received little attention
      until the last three decades. Sleep disorders seen in PD patients include
      insomnia, excessive sleepiness, restless legs syndrome, REM sleep behavior
      disorder. Some of these can have significant impact and lower the quality of life
      in these patients. An understanding of sleep issues in PD can help identify them
      early and result in optimal management.

PMID- 30228641
TI  - Persistent Elevation of Thyroglobulin in Patient Treated for Differentiated
      Thyroid Cancer: A Ten-Year Review.
AB  - Differentiated Thyroid Cancer (DTC) is increasing in prevalence due to better
      diagnostic tools and excellent long-term survival. This study is to understand
      the outcome of twenty-six patients with DTC over a period of 10 years after the
      initial treatment with surgery and radioiodine therapy. Our study analysis showed
      no deaths, and indicated that older men were more likely to have persistent
      disease. Further studies are needed to focus on cost effective long-term
      management of DTC.

PMID- 30228642
TI  - Uveitis Following Treatment of Verruca Vulgaris with Intralesional Candida
      Antigen.
AB  - This is a first literature report of a case of uveitis along with severe systemic
      symptoms following verruca vulgaris treatment with intralesional Candida antigen.
      We believe the Candida injection was causative.

PMID- 30228643
TI  - Comparison of High-Fidelity Medical Simulation to Short-Answer Written
      Examination in the Assessment of Emergency Medicine Residents in Medical
      Toxicology.
AB  - We compared high-fidelity medical simulation to short-answer written examination
      in the assessment of emergency medicine residents (EMR) on a month-long medical
      toxicology rotation. Knowledge-based assessment tools using cases of an aspirin
      overdose and a tricyclic antidepressant overdose were used to assess all
      consecutive rotating EMR (n=53). Assessment by simulation had similar accuracy
      and precision but higher satisfaction rates when compared to written examination.
      Incorporating simulation into the ABEM certifying examination warrants further
      study.

PMID- 30228644
TI  - Missouri Medicine Annual Statement of Ownership, Management & Circulation.

PMID- 30228645
TI  - Saying Good-Bye to a Good Man Doing a Great Job: Tom Holloway.

PMID- 30228646
TI  - 2017: A Signal Year's Review at Missouri Medicine.

PMID- 30228647
TI  - Forecast for 2018 Legislative Session.

PMID- 30228648
TI  - Stay Out of the Emergency Room - Or Else.

PMID- 30228649
TI  - Physician Advocacy: The AMA Interim Meeting 2017.

PMID- 30228650
TI  - Reframing the Relevance: Engaging Residents and Fellows in Organized Medicine.

PMID- 30228651
TI  - Thoughts on Medical Education.

PMID- 30228652
TI  - Data Integration and e-Commerce Threats Challenging Providers.

PMID- 30228653
TI  - Innovative Assistant Physician Program Enhances Patient Care: The Nevada Medical
      Clinic Experience.

PMID- 30228654
TI  - One Common Hope: To Be Healed.

PMID- 30228655
TI  - Missouri's Bootheel: A Special Place.

PMID- 30228656
TI  - A Legacy for the Missouri Physicians Health Program.

PMID- 30228657
TI  - MSMA Members in the News.

PMID- 30228658
TI  - 1 picture = 1,000 words.

PMID- 30228659
TI  - 160th Annual Convention, March 23-25, 2018 | Renaissance St. Louis Airport Hotel
      www.msma.org/annual-convention.

PMID- 30228660
TI  - General Sessions & Events.

PMID- 30228661
TI  - Super Bugs and Antimicrobial Stewardship.

PMID- 30228662
TI  - The Opioid Crisis in Missouri: A Call to Action for Physicians, Legislators, and
      Society.
AB  - Opioid overdose deaths in the United States increased sharply over the last
      decade leading the President to declare a national emergency. The neurobiology of
      opioid addiction is explored in conjunction with the historical events preceding
      the current epidemic. A patient-centric perspective is provided along with
      rationale for contemporary Medical Assisted Therapy (MAT) options to safely
      reduce overdose deaths and other preventable consequences of prescription misuse
      and heroin abuse. A multidisciplinary medical provider approach is essential, in
      addition to legislative efforts to reduce current regulatory burdens that reduce
      access to MAT in many settings. This review introduces a new Missouri Medicine
      series intended to explore key concepts to simultaneously reduce opioid
      prescribing, while effectively managing acute and chronic pain across complex
      healthcare settings.

PMID- 30228663
TI  - Improving Emergency Department Care for Aging Missourians: Guidelines,
      Accreditation, and Collaboration.
AB  - Aging baby-boomers present significant challenges to accessible, affordable
      emergency care in America for patients of all ages. St. Louis physicians served
      as early innovators in the field of geriatric emergency medicine. This manuscript
      summarizes a multi-institutional November 2016 symposium reviewing the Missouri
      history of geriatric emergency care. In addition, this manuscript describes
      multispecialty organizations' guidelines, healthcare outcomes research,
      contemporary medical education paradigms, and evolving efforts to disseminate
      guideline-based geriatric emergency care using a "Boot Camp" approach and
      implementation science. This manuscript also reviews local adaptations to
      emergency medical services and palliative care, as well as the perspectives of
      emergency department leaders exploring the balance between infrastructure and
      personnel required to promote guideline-based geriatric emergency care with the
      anticipated benefits. This discussion is framed within the context of the
      American College of Emergency Physician's planned geriatric emergency department
      accreditation process scheduled to begin in 2018.

PMID- 30228664
TI  - Sleep and Epilepsy: A Complex Interplay.
AB  - In this review we look to provide an overview of the complex interactions between
      sleep and epilepsy, and how knowledge of the interplay between the two can help
      in guiding management of disorders in both areas.

PMID- 30228665
TI  - Acute Aortic Syndromes: Diagnosis and Treatment.
AB  - Acute aortic syndromes are disorders of the thoracic and abdominal aorta that are
      usually symptomatic and require urgent evaluation and treatment. They include
      acute aortic dissection, intramural hematoma, and penetrating atherosclerotic
      ulcer. Knowledge of the natural history of these conditions, prompt diagnosis,
      and surgical intervention, when indicated, are the keys to successful outcomes.

PMID- 30228667
TI  - Where Does the Money Go?

PMID- 30228666
TI  - The Microvascular and Macrovascular Benefits of Fibrates in Diabetes and the
      Metabolic Syndrome: A review.
AB  - Background: The purpose of this article is to discuss the evidence regarding
      potential macrovascular and microvascular benefits of fibrate therapy in general
      and fenofibrate specifically. Methods: We performed a literature review
      summarizing the results of studies testing fibrates on relevant. Results:
      Although statins are the first line therapy with an unparalleled amount of
      evidence for reducing the risk of cardiovascular disease (CVD) in patients with
      dyslipidemia and the metabolic syndrome (MetS), there are several landmark
      studies that have focused on the potential benefits of fibrate therapy for
      reducing CVD risk. Fibrates confer benefits mostly for patients with diabetes
      mellitus (DM), MetS, and atherogenic dyslipidemia. Recently, many studies have
      shown that fibrates confer benefits on the vascular system as well as the liver
      and kidneys. Fibrates also have demonstrable benefits in cohorts of patients with
      DM and renal disease. Conclusions: Fibrates appear to provide significant
      microvascular and macrovascular benefits particularly in patients with DM, MetS,
      or renal disease.

PMID- 30228668
TI  - Population Health Management and ACOs: Will They Achieve Their Goals of Better
      Health and Lower Costs?

PMID- 30228669
TI  - Don't Blame Doctors for Medication Nonadherence.

PMID- 30228671
TI  - The MSMA Headquarters Staff: Exceptional Service and Professionalism.

PMID- 30228670
TI  - Hungering for Immortality.
AB  - Beyond avoiding risky behavior-smoking, substance abuse, obesity-and embracing
      healthy habits like exercise, a balanced diet, and non-obese body weight, are
      there things we each do today to significantly extend our lifespan? Caloric
      restriction is the only behavioral intervention consistently shown to extend both
      mean and maximal lifespan across a wide range of species. In most cases, the
      lifespan extension is accompanied by a marked delay in the onset of age
      associated disease and infirmity.

PMID- 30228672
TI  - The Team That Wins.

PMID- 30228673
TI  - Annual Grant to a Missouri Physicians-led Free Clinic is now available from the
      AMA Foundation.

PMID- 30228674
TI  - A "Thank You" to the American Medical Association.

PMID- 30228675
TI  - Contributors to the MPHP 2017 Fund Raising Campaign.

PMID- 30228677
TI  - 160th Annual Convention March 23-25, 2018 | Renaissance St. Louis Airport Hotel
      www.msma.org/annual-convention.

PMID- 30228676
TI  - Errata.
AB  - [This corrects the article on p. 417 in vol. 114.][This corrects the article on
      p. 433 in vol. 114.].

PMID- 30228678
TI  - General Sessions & Events.

PMID- 30228679
TI  - Research at A.T. Still University's Kirksville College of Osteopathic Medicine.

PMID- 30228680
TI  - Maintaining Balance in Medical School through Medical Humanities Electives.
AB  - The amount of scientific and medical information students are expected to master
      is ever increasing. This may draw attention away from the human aspect of
      medicine - the reason most enter medical school in the first place. Medical
      humanities may help students remain empathetic, self-aware and reflective as they
      work to become excellent physicians.

PMID- 30228681
TI  - Integration of Ultrasonography into the Undergraduate Medical Curriculum: Seven
      Years of Experience.
AB  - Ultrasound education has been part of the curriculum at A.T. Still University's
      Kirksville College of Osteopathic Medicine for over seven years (since 2011), and
      has been successfully integrated into the first two years of the four-year
      medical school curriculum. Students master ultrasound techniques through hands-on
      laboratories covering all body regions and systems. Ultrasound training has the
      potential to enhance the medical school learning experience for students and
      improve the quality of their future patient care.

PMID- 30228682
TI  - Integration of 3-Dimensional/4-Dimensional Ultrasound Technology into
      Undergraduate Medical Education: Student Perception of Innovative Obstetrics
      Education.
AB  - The current study assessed level of comfort of medical students using 3
      dimensional/4-dimensional (3D/4D) ultrasound technology after participating in an
      obstetrical ultrasound educational activity. The majority of students agreed that
      they were capable of performing and interpreting 2-dimensional and 3D/4D
      obstetrical ultrasounds and that the training benefited their clinical decision
      making skills. Additionally, students agreed that access to 3D/4D ultrasound
      technology would encourage patients to seek physician care and act as a useful
      tool for patient education.

PMID- 30228683
TI  - Introduction of a Combined Gastrointestinal Histopathology Laboratory Exercise
      into an Undergraduate Medical School Curriculum.
AB  - To improve training in histology and pathology, an integrative, case-based
      histopathology laboratory exercise that used virtual microscopy was offered to
      first-year medical students during the KCOM gastrointestinal block. Students
      showed improvement in their understanding of histology and pathology after
      completing the exercise. Most students agreed that the combined histopathology
      laboratory helped them improve their understanding of histology and pathology in
      the gastrointestinal system and link normal histological and pathological changes
      to better understand disease processes.

PMID- 30228684
TI  - A Comparison of Point-of-Care Ultrasonography Use in Rural Versus Urban Emergency
      Departments Throughout Missouri.
AB  - We surveyed emergency department directors at 56 Missouri hospitals about
      availability of ultrasound equipment, primary uses for ultrasonography, and
      factors that could increase ultrasonography use in the emergency departments.
      Results indicated large-sized hospitals, typically in urban areas, used
      ultrasonography more than medium-sized or small-sized hospitals. Lack of
      ultrasound equipment and appropriately trained physicians contributed to limited
      use of ultrasonography in small-sized hospitals, typically in rural areas.

PMID- 30228686
TI  - Implementation of Oral Case Presentations in an Immunology Course.
AB  - Implementation of oral case presentations (OCP) in the Immunology course at A.T.
      Still University-Kirksville College of Osteopathic Medicine has significantly
      improved written examination scores and student satisfaction with the course by
      enhancing its clinical relevance. With six faculty facilitators, an average class
      size of 172 students can complete the exercise in a single day. The exercise
      requires small group meeting rooms, each equipped with a computer and wall
      mounted monitor, but no other physical resources.

PMID- 30228685
TI  - Gross Anatomy Education Today: The Integration of Traditional and Innovative
      Methodologies.
AB  - The current study surveyed first-year osteopathic medical students about
      dissection, multimedia dissector, split laboratories, VH (virtual human)
      dissector, ultrasonography, and prior experience of anatomical concepts. Students
      perceived cadaveric dissection, multimedia dissector, and ultrasonography
      laboratories as important contributors for learning anatomy. Students felt
      cadaveric dissection was an important factor in their medical school selection.
      Study results suggested students perceived integrated anatomy courses that
      utilized dissection and multimodal approaches to deliver anatomical information
      as highly effective.

PMID- 30228687
TI  - Human Patient Simulation as a Teaching Tool.
AB  - The KCOM campus hosts a modern, state of the art human patient simulation (HPS)
      laboratory, which allows simulation of neonatal, pediatric, obstetric, and adult
      patients. Students are able to utilize the HPS lab to become comfortable with
      physical exam skills, procedural skills and communication skills before
      attempting them in a true clinical environment. Involvement of students from
      other disciplines has facilitated interprofessional education. Involvement of
      community health providers has expanded the richness of the student experience.

PMID- 30228688
TI  - Medical Applications for 3D Printing: Recent Developments.
AB  - This is a review of some of the recent developments in the application of 3D
      printing to medicine. The topic is introduced with a brief explanation as to how
      and why 3D is changing practice, teaching, and research in medicine. Then, taking
      recent examples of progress in the field, we illustrate the current state of the
      art. This article concludes by evaluating the current limitations of 3D printing
      for medical applications and suggesting where further progress is likely to be
      made.

PMID- 30228689
TI  - Small Incision Lenticule Extraction SMILE - The Future of Refractive Surgery is
      Here.
AB  - Small Incision Lenticule Extraction (SMILE) is a relatively new one-step
      refractive procedure that has recently been approved by the FDA for the treatment
      of myopia. It is anticipated myopic astigmatism will be FDA-approved in 2019. The
      SMILE procedure is shown to have similar efficacy, safety, predictability, and
      stability as current surgical options, such as LASIK, but has been gaining
      popularity due to fewer potential complications, such as dry eye incidence and
      greater biomechanical stability, and faster recovery time. This article discusses
      the SMILE procedure, its benefits, risks, uncertainties, and potential future in
      the world of refractive surgery.

PMID- 30228691
TI  - Marathon Running: An Unhealthy Addiction!

PMID- 30228690
TI  - Hypersomnia.
AB  - Adequate alertness is necessary for proper daytime functioning. Impairment of
      alertness or increase in sleepiness results in suboptimal performance and
      adversely affects the quality of life. While some causes of somnolence are
      intrinsic to the brain circuitry and neurochemical architecture, others are due
      to maladaptive behaviors and disorders affecting the normal sleep homeostasis.
      Identification of the problem and understanding the underlying etiology is the
      key to timely treatment and better outcomes.

PMID- 30228693
TI  - Residency: Training for Burnout.

PMID- 30228692
TI  - The Goldilocks Zone for Exercise: Not Too Little, Not Too Much.
AB  - Homo sapiens are evolutionarily adapted to be very physically active throughout
      life, and thus habitual physical activity (PA) is essential for well-being and
      longevity. Never the less, middle-aged and older individuals engaging in
      excessive strenuous endurance exercise appear to be at increased risk for a
      variety of adverse cardiovascular (CV) effects including atrial fibrillation,
      myocardial fibrosis, and coronary atherosclerosis. An emerging body of evidence
      indicates U-shaped or reverse J-shaped curves whereby low doses and moderate
      doses of PA significantly reduce long-term risks for both total mortality and CV
      mortality, however, at very high doses of chronic strenuous exercise much of the
      protection against early mortality and CV disease is lost. The optimal dose, or
      what we term 'Goldilocks Zone,' of PA may be: at least 150 minutes per week of
      moderate-intensity aerobic exercise or 75 minutes per week of vigorous-intensity
      aerobic activity, but not more than four to five cumulative hours per week of
      vigorous (heart-pounding, sweatproducing) exercise, especially for those over 45
      years of age. It is also important to take at least one day per week off from
      vigorous exercise. There appears to be no concerns about an upper threshold for
      safety for leisure-time low-to-moderate intensity activities such as walking at a
      comfortable pace, housework, gardening, etc. After every 30 consecutive minutes
      spent sitting, stand up and move, ideally walking briskly for about five minutes.

PMID- 30228694
TI  - We Need to Reflame the Fire Before It Burns Out.

PMID- 30228695
TI  - The Private Physician Practice's Early Planning Considerations Under the New Tax
      Law.

PMID- 30228696
TI  - Be Involved!

PMID- 30228698
TI  - Actions from 2018 Legislative Session.

PMID- 30228697
TI  - Missouri Physicians Keep Our Local Economy Healthy.

PMID- 30228699
TI  - MSMA Members in the News.

PMID- 30228700
TI  - FDA Approves Direct-to-Consumer Cancer Genomics.

PMID- 30228701
TI  - The Future of the American Health Care System.

PMID- 30228702
TI  - Project Apache and Pediatric Care.

PMID- 30228703
TI  - Prostate Cancer Review.

PMID- 30228704
TI  - Prostate Cancer: Update on Early Detection and New Biomarkers.
AB  - Screening and early treatment of prostate cancer (PCa) has recently come under
      scrutiny due to the rates of overdiagnosis of low risk cancer. Randomized trials,
      including ERSPC and PLCO, have informed our understanding of the survival benefit
      provided by systematic PCa screening with serum prostate-specific antigen (PSA).
      To reduce the number of patients diagnosed with indolent disease, new adjuvant
      risk stratification tests have become available.

PMID- 30228705
TI  - Imaging in Prostate Cancer: Magnetic Resonance Imaging and Beyond.
AB  - Imaging is becoming critical for guiding management decisions in prostate cancer
      (PCa) both at initial diagnosis and at recurrence. Multiparametric magnetic
      resonance imaging (mpMRI) and positron emission tomography (PET) of the prostate
      have proven valuable in the detection and localization of aggressive disease.
      Therefore, understanding the indications for mpMRI, imaging techniques and
      interpretation, limitations of current imaging approaches, and utility of PET and
      simultaneous PET/MRI has become increasingly important.

PMID- 30228706
TI  - Surgical Management for Prostate Cancer.
AB  - For prostate cancer, radical prostatectomy remains the gold standard for surgical
      management. Given the side effects associated with surgery, patients at low risk
      of prostate cancer-specific mortality should consider active surveillance under
      the guidance of a urologist to safely delay intervention. For patients with an
      intermediate risk of cancer-specific mortality and otherwise healthy life
      expectancy, radical prostatectomy has been demonstrated to improve survival.
      Finally, even for select patients with advanced prostate cancer-metastatic
      disease to the lymph nodes or distant sites-radical prostatectomy may provide a
      survival benefit.

PMID- 30228707
TI  - Radiation Therapy for Prostate Cancer.
AB  - Annually, there are nearly 3000 new cases and 500 deaths from prostate cancer in
      Missouri. When treatment is appropriate and necessary, radiotherapy offers
      similar cure rates to prostatectomy, with fewer long-term sexual side effects and
      little effect on urinary continence. Radiotherapy is delivered with external beam
      or implanted radioactive sources (brachytherapy). In high-risk disease,
      combinations of external beam and brachytherapy offers improved biochemical
      control. Following prostatectomy, salvage radiotherapy should be initiated as
      soon as possible.

PMID- 30228708
TI  - Prostate Cancer Pathology: Recent Updates and Controversies.
AB  - Prostate cancer is common, and recent efforts in clinical management have focused
      on identifying patients who could be candidates from less aggressive management
      or who could benefit from more aggressive therapy. As prostate cancer histology,
      especially Gleason score, plays a critical role in predicting patient outcomes,
      attempts have been made to refine histologic classification and reporting in
      prostate cancer to facilitate patient risk stratification. This review discusses
      recent updates in prostate cancer grading and reporting.

PMID- 30228709
TI  - Treatment of Advanced Prostate Cancer.
AB  - Advanced prostate cancer is a heterogenous disease with multiple treatment
      options. Patients with advanced disease are stratified based evidence of
      metastasis and sensitivity to hormone therapy. Men with hormone sensitive disease
      are treated with androgen deprivation therapy and possibly chemotherapy. The
      treatment options for men with castrate resistant disease are rapidly evolving
      with multiple recently approved treatment options. Determining the proper
      sequence and combination of these therapies remains a work in progress.

PMID- 30228710
TI  - Prevalence of Tick-Borne Pathogens in Northeast Missouri.
AB  - We evaluated Amblyomma americanum (lone star tick) and Dermacentor variabilis
      (American dog tick) in northeast Missouri for the presence of Borrelia,
      Ehrlichia, and Rickettsia bacteria and Heartland virus. We screened 436
      individual adult lone star ticks (86% of all ticks collected) and infection rates
      were 6% for B. lonestari, 19% for E. chaffeensis, 3% for E. ewingii, 36% for R.
      amblyommatis, and 1% for R. montanensis. In the 189 individual American dog
      ticks, infection rates were 19% for E. chaffeensis, 15% for E. ewingii, 4% for R.
      amblyommatis, and 5% for R. montanensis. In addition, we screened 20 pools of
      adults and 30 pools of nymphs for the Heartland virus which was not detected.
      Understanding the presence and epidemiology of these causative (E. chaffeensis
      and E. ewingii) and suspected (B. lonestari, R. amblyommatis, and R. montanensis)
      agents in Missouri should increase awareness of potential tick-borne disease in
      the medical community.

PMID- 30228712
TI  - Member Services Information.

PMID- 30228711
TI  - Sleep Medicine: Parasomnias.
AB  - Parasomnias are abnormal and undesirable behaviors during sleep and are thought
      to be due to the sleep state instability. Some of them are benign, while some of
      them point to a possible underlying neurodegenerative process. This article
      briefly discusses the clinical characteristics, demographics, and pathophysiology
      of major parasomnias and associated disorders. The classification outlined in
      this article conforms to the current version of International Classification of
      Sleep disorders.

PMID- 30228713
TI  - How Do We Approach Anti-Vaccination Attitudes?
AB  - There are many things that, as physicians, we universally take for granted. One
      does not need a background in medical statistics to understand that seat belts
      save lives and reduce injuries in car accidents. Nor do you need to have an
      epidemiology degree to know that tobacco smoking is causative for lung cancer. At
      some point in your undergraduate classes, you almost certainly heard the story of
      Edward Jenner, the milkmaids, and the resulting smallpox vaccine. Thanks to Dr.
      Jonas Salk, a true hero of the 20th Century, the last U.S. polio case was in
      1979.1 The benefits of vaccination clearly outweigh the risks. Therefore measles,
      mumps, rubella and diphtheria should be nearly unknown today ... right?

PMID- 30228714
TI  - Part I: The 1918 Influenza in Missouri: Centennial Remembrance of the Crisis.

PMID- 30228715
TI  - Prescription Opioid Misuse and Overuse in the U.S.

PMID- 30228716
TI  - Why Marijuana Will Not Fix the Opioid Epidemic.

PMID- 30228717
TI  - Toxic Work Environment.

PMID- 30228718
TI  - Coffee Is Not a Carcinogen.

PMID- 30228719
TI  - MSMA Members in the News.

PMID- 30228720
TI  - The Case for Organized Medicine: Why You Should Get Involved.

PMID- 30228721
TI  - Transforming Excellence in Academic Medicine.

PMID- 30228722
TI  - Feature Series Overview.

PMID- 30228723
TI  - Dysphagia.
AB  - A complaint of dysphagia suggests difficulty in swallowing and is characterized
      based on the symptoms and location of pathology. Oropharyngeal dysphagia is
      typically due to difficulty initiating a swallow and is generally due to
      structural, anatomic or neuromuscular abnormalities. Esophageal dysphagia arises
      after the swallow and causes include intrinsic structural pathology, extrinsic
      compression, or disruption in normal motility. Etiologies, methods of evaluation,
      and management options of dysphagia are reviewed here.

PMID- 30228724
TI  - Barrett's Esophagus.
AB  - The prevalence of Barrett's esophagus is increasing in the United States and is a
      major risk factor for esophageal adenocarcinoma. This review serves to help
      primary care physicians and family practitioners better understand who should be
      screened for Barrett's esophagus, know the appropriate surveillance intervals for
      repeat endoscopy, and understand therapeutic options for the management of
      Barrett's esophagus.

PMID- 30228725
TI  - Gastroesophageal Reflux Disease (GERD).
AB  - Gastroesophageal reflux disease (GERD) is a common clinical problem, affecting
      millions of people worldwide. Patients are recognized by both classic and
      atypical symptoms. Acid suppressive therapy provides symptomatic relief and
      prevents complications in many individuals with GERD. Advances in diagnostic and
      therapeutic modalities have improved our ability to identify and manage disease
      complications. Here, we discuss the pathophysiology and effects of GERD, and
      provide information on the clinical approach to this common disorder.

PMID- 30228726
TI  - Peptic Ulcer Disease and Helicobacter pylori infection.
AB  - Peptic ulcer disease (PUD) is a common condition that both primary care providers
      and gastroenterologists encounter. Symptoms of peptic ulcer disease are variable
      and may include abdominal pain, nausea, vomiting, weight loss and bleeding or
      perforation with complicated disease. Identifying the risk factors and mechanisms
      that lead to the development of PUD helps to understand the approach behind
      diagnostic and treatment strategies.

PMID- 30228727
TI  - NASH: The Emerging Most Common Form of Chronic Liver Disease.
AB  - Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease
      that can progress to cirrhosis and hepatocellular carcinoma. This review provides
      brief answers to common questions clinicians may have about NASH. The diagnosis
      of NASH currently requires a liver biopsy, although non-invasive tests are being
      evaluated and may supplant liver biopsy in the near future. Treatment is focused
      on lifestyle modifications, with new medications currently in clinical trials.

PMID- 30228728
TI  - Pancreatic Adenocarcinoma.
AB  - Pancreatic cancer is a common gastrointestinal malignancy, and is often
      associated with a poor prognosis. Challenges to effective screening for
      pancreatic cancer include low disease prevalence and high cost of screening
      modalities such as endoscopic ultrasound and cross-sectional imaging. Further,
      most patients are asymptomatic during the early course of disease, which often
      leads to delay in diagnosis. Treatment options include surgery, chemotherapy, and
      palliative care.

PMID- 30228729
TI  - Constipation: Evaluation and Management.
AB  - Constipation is defined as the infrequent passage of stools or difficulty with
      evacuation of stools. Constipation can be classified as primary or secondary, and
      primary constipation can be further divided into slow transit constipation or
      outlet obstruction. The diagnostic workup involves focused lab tests and
      structural evaluation, followed by a therapeutic trial of fiber and laxatives,
      and finally, specialized tests. Treatment can consist of dietary changes,
      medications, physical therapy, and possibly surgery in refractory cases.

PMID- 30228730
TI  - A Bridge to Nowhere? Challenging Outpatient Transitions of Care for Acute Pain
      Patients in the Opioid Epidemic Era.
AB  - Opioid misuse is reducing Americans' life expectancy, thereby catalyzing
      professional societies and legislators to action. Efforts to combat the opioid
      epidemic must work hand-in-hand with appropriate efforts to reduce the severity
      and duration of suffering. Pharmacologic analgesia is temporizing. Current opioid
      prescribing guidelines focus on reducing the frequency and quantity of narcotics
      prescribed, but lack attention to alleviation of the source of pain. Conditions
      eliciting acute pain sometimes require additional specialist management following
      discharge from the emergency department. Patients frequently lack timely access
      to these specialists, particularly if underinsured. This essay explores acute
      dental pain, extremity fractures, and back pain as three common examples whereby
      complex healthcare systems must efficiently adapt in order to serve the dual
      objectives of reducing the risk of opioid-related adverse consequences and
      minimizing the duration of patient suffering.

PMID- 30228732
TI  - IgG-4 Related Disease: An Introduction.
AB  - IgG4-related disease (IgG-RD) describes a group of fibroinflammatory diseases
      that affect a variety of tissues resulting in tumor-like effect and/or organ
      dysfunction. Clinical presentation varies according to the tissue(s) involved,
      and diagnosis relies on tissue findings of dense infiltration of IgG4-positive
      plasma cells and a characteristic storiform fibrosis. Treatment is mainly with
      glucocorticoids, while multiple immunosuppressive medications can be used as
      adjuvant agents. Rituximab has showed promising results, but further studies are
      needed.

PMID- 30228731
TI  - Not Salt But Sugar As Aetiological In Osteoporosis: A Review.
AB  - Salt has notoriously been blamed for causing an increase in the urinary excretion
      of calcium, and thus is a considered a risk factor for osteoporosis. However, the
      increase in the urinary excretion of calcium with higher sodium intakes can be
      offset by the increased intestinal absorption of dietary calcium. Thus, the
      overall calcium balance does not appear to be reduced with a higher sodium
      intake. However, the other ubiquitous white crystal, sugar, may lead to
      osteoporosis by increasing inflammation, hyperinsulinemia, increased renal acid
      load, reduced calcium intake, and increased urinary calcium excretion. Sugar, not
      salt, is the more likely white crystal to be a risk factor for osteoporosis when
      overconsumed.

PMID- 30228733
TI  - Meet MSMA's 2018-2019 President.

PMID- 30228735
TI  - State of the Association: Presidential Address.

PMID- 30228734
TI  - Alliance Installs 2018-2019 President.

PMID- 30228737
TI  - Recipients of the 50-Year Physician Pin.

PMID- 30228736
TI  - Physicians Are More Than Just Providers.

PMID- 30228739
TI  - Sponsors & Exhibit Partners.

PMID- 30228738
TI  - 160th House of Delegates Resolution Actions & Decisions.

PMID- 30228740
TI  - MSMA Elects Leadership.

PMID- 30228741
TI  - Summary of Council Actions: 2017-2018.

PMID- 30228743
TI  - Missouri State Medical Association Financial Statement.

PMID- 30228742
TI  - Reports of the Delegate Handbook: 2017-2018.

PMID- 30228744
TI  - Missouri Physicians Health Program Financial Statement.

PMID- 30228745
TI  - 2018 Annual Convention Attendance.

PMID- 30228746
TI  - USPSTF: Quit Clowning Around with Our Health!

PMID- 30228747
TI  - Poisoning, Overdoses, Toxic Exposures.
AB  - The national poison center movement originated in the Midwest with actions of the
      American Academy of Pediatrics in Chicago, Illinois, in 1972. The Missouri Poison
      Center (MPC) was established in 1974. The MPC and other regional poison centers
      are essential to the public health locally and nationally. Trends in serious
      poisoning outbreaks such as the release of synthetic cannabinoids have been
      detected by real-time electronic surveillance by specialists in poison
      information and medical toxicologists.

PMID- 30228748
TI  - Hemp & Cannabidiol: What is a Medicine?

PMID- 30228750
TI  - Streamlining the Insurance Prior Authorization Debacle.

PMID- 30228749
TI  - Unemployed Physicians.

PMID- 30228751
TI  - The Onerous Rules of the American Board of Internal Medicine and the National
      Quality Forum Reward Bureaucrats, Undermine Physician Morale, and Do Not Improve
      Patient Care.

PMID- 30228752
TI  - The 1918 Influenza in Missouri: Centennial Remembrance of the Crisis.

PMID- 30228754
TI  - Quo Vadis?

PMID- 30228753
TI  - Continuing Obligations Following the Unexpected Death of a Physician: Things to
      Keep in Mind.

PMID- 30228755
TI  - Physician Advocacy: The AMA Annual Meeting 2018.

PMID- 30228757
TI  - YPS Report: The Role of Private Equity in Medicine.

PMID- 30228756
TI  - Rising Leaders: Residents and Fellows at AMA Annual 2018.

PMID- 30228758
TI  - Inspiring Member Physicians to Achieve Quality Medicine.

PMID- 30228759
TI  - MSMA Members in the News.

PMID- 30228760
TI  - USPSTF Update of Guidelines on Early Detection of Prostate Cancer.

PMID- 30228761
TI  - Beating the Odds on Lifespan.

PMID- 30228762
TI  - Welcome to Managed Care and Legal Fear.

PMID- 30228763
TI  - Recent Recognitions Highlight Strengths of Innovative UMKC School of Medicine.

PMID- 30228764
TI  - Pediatric Medicine Nurtures, Heals, and Impacts the Future.

PMID- 30228766
TI  - Imaging the Pediatric Athlete: Acute and Stress Skeletal Injuries.
AB  - Sports-related traumatic injuries in children have increased in tandem with
      participation in higher level activities. The developing musculoskeletal
      structures in children are susceptible to unique injuries that vary with location
      and the stage of skeletal maturation. The imaging evaluation of sports injuries
      in children presents several unique challenges. The purpose of this article is to
      educate the reader on injuries unique to the skeletally immature athlete with
      focus on their imaging evaluation and diagnosis.

PMID- 30228765
TI  - Digital Tomosynthesis Applications in Pediatric Orthopedic Imaging: A Case
      Series.
AB  - Digital tomosynthesis (DTS) is an emerging technology that provides cross
      sectional, three-dimensional imaging similar to computed tomography (CT) at a
      fraction of the radiation dose and cost. In this article, we describe multiple
      cases where our pediatric orthopedic surgeons have used DTS imaging to help in
      clinical management of fracture healing.

PMID- 30228767
TI  - Advances in Pediatric Cardiovascular Imaging.
AB  - Cardiac imaging plays a key role in the accurate diagnosis of pediatric
      congenital heart disease (CHD). Echocardiography and catheter angiography are
      traditionally used to delineate cardiac anatomy. CT and MRI imaging offer a non
      invasive way to image cardiovascular anatomy which can be used in conjunction
      with echocardiography for the diagnosis and treatment planning for CHD. These
      modalities can depict the morphology and relationship to surrounding structures
      better than echocardiography, especially in complex congenital defects.

PMID- 30228768
TI  - Pediatric Interventional Radiology: Blurring the Lines Between Specialties.
AB  - Medical imaging has transformed the ease and speed of patient care with provision
      of detailed evaluation of anatomic structures and disease processes.
      Interventional radiology uses imaging guided techniques to further diagnose or
      treat diseases with minimally invasive methods. These techniques are particularly
      helpful in treating pediatric patients.

PMID- 30228769
TI  - Pre-Surgical Planning: Multimodality Imaging to Optimize Outcomes in Pediatric
      Epilepsy Surgery.
AB  - Neuroimaging is an important component of the pre-surgical planning for pediatric
      epilepsy. High-resolution structural magnetic resonance images are combined with
      advanced structural and functional imaging techniques to better define the
      surgical lesion and decrease morbidity postoperatively. The combination of
      neuroimaging, electroencephalography (EEG), and neuropsychiatric testing in a
      multidisciplinary epilepsy conference setting is essential for determining a plan
      for surgical management.

PMID- 30228770
TI  - Emerging Technology and Applications of 3D Printing in the Medical Field.
AB  - 3D printing technology evolved in the 1980s, but has made great strides in the
      last decade from both a cost and accessibility standpoint. While most printers
      are employed for commercial uses, medical 3D printing is a growing application
      which serves to aid physicians in the diagnosis, therapeutic planning, and
      potentially the treatment of patients with complex diseases. In this article we
      will delineate the types of printers available to the consumer, the various
      materials which can be utilized, and potential applications of 3D models in the
      healthcare field.

PMID- 30228771
TI  - Exposure to Ticks and their Pathogens in Northeast Missouri.
AB  - While the prevalence of human pathogens has been quantified in ticks in Adair
      County, Missouri, the prevalence of residents acquiring tick-borne diseases and
      seeking medical treatment has not. A public survey (n=109) revealed that 96% of
      respondents reported finding attached ticks on their person; of these, 38%
      developed symptoms post tick bite; of these, 55% reported consultation with a
      health care provider. Overall, 89% of practitioners surveyed had treated at least
      one patient for tick-borne disease. Rocky Mountain spotted fever and Lyme disease
      were the most common illnesses diagnosed, however, the only confirmed cases
      reported by Missouri Department of Health and Senior Services from 2013-2017 were
      ehrlichiosis. Results from these surveys indicate that exposure to ticks is
      common and ehrlichiosis infections are likely underdiagnosed while Rocky Mountain
      spotted fever and Lyme disease are likely overdiagnosed.

PMID- 30228772
TI  - Buying Some Piece of Mind if You Get 'Ticked-off'.

PMID- 30228774
TI  - Member Services Information.

PMID- 30228775
TI  - Electromagnetic simulation for diagnosing damage to femoral neck vasculature: A
      feasibility study.
AB  - Background: Femoral neck fractures are common injuries managed by orthopedic
      surgeons across the world. From pediatrics to geriatrics, disruption of the blood
      supply to the femoral neck is a well-recognized source of morbidity and
      mortality, oftentimes resulting in avascular necrosis of the femoral head. This
      devastating complication occurs in 10-45% of femoral neck fractures. Therefore,
      it is vital for orthopedic surgeons provide efficient treatment of this injury,
      in order to optimize the patient's potential outcome and prevent long-term
      sequelae. Methods: In this study, the anatomy of the proximal femur, including
      femoral metaphysis, femoral neck, vasculature, and femoral head, were simulated
      in COMSOL Finite Element Analysis (FEA) software. Electric fields were generated
      in a fashion that exploited disruptions within the vasculature of the femoral
      neck. This study was aimed at developing an alternative imaging modality for
      narrowing or disrupting the femoral neck's vasculature. The variables used for
      investigation included: frequency, penetration depth, and magnitude of the
      electrical energy. These variables, when combined, allowed for enhanced simulated
      visualization of the vasculature of the femoral neck and theoretically expedited
      diagnosis of obvious, or occult, femoral neck injury. Results: Simulated blood
      vessels were developed in two-dimensions: the phi direction (circular), and z
      direction. Two different frequencies, 3 GHz, and 5 GHz were considered, with 100
      J energy pulses within blood vessels of 2.54 mm in diameter. The fat surrounding
      the bone to the outside surface body was simulated at 0.25 inch (0.65 cm). An
      additional model, with layered fat and skin above the vessels, was simulated at
      2000J and successfully able to visualize the femoral neck's blood vessels.
      Results showed a distinguished E field across the blood boundary of nearly 170
      V/M. Conclusions: The electric field simulation data within the Phi and Z
      directions promises the feasibility of a subsequent practical model.

PMID- 30228773
TI  - Sleep Medicine: Restless Legs Syndrome.
AB  - Restless Legs Syndrome is a highly prevalent sensorimotor disorder characterized
      by urge to move the legs due to discomfort that primarily happens in the evening
      or at nights. Although the exact pathophysiology remains unclear, brain iron
      deficiency and altered dopaminergic function appears to play an important role in
      the pathogenesis of this condition. This disorder affects women more frequently
      and is associated with significant morbidity.

PMID- 30228776
TI  - Clinical impact of microbiome in patients with decompensated cirrhosis.
AB  - Cirrhosis is an increasing cause of morbidity and mortality. Recent studies are
      trying to clarify the role of microbiome in clinical exacerbation of patients
      with decompensated cirrhosis. Nowadays, it is accepted that patients with
      cirrhosis have altered salivary and enteric microbiome, characterized by the
      presence of dysbiosis. This altered microbiome along with small bowel bacterial
      overgrowth, through translocation across the gut, is associated with the
      development of decompensating complications. Studies have analyzed the
      correlation of certain bacterial families with the development of hepatic
      encephalopathy in cirrhotics. In general, stool and saliva dysbiosis with
      reduction of autochthonous bacteria in patients with cirrhosis incites changes in
      bacterial defenses and higher risk for bacterial infections, such as spontaneous
      bacterial peritonitis, and sepsis. Gut microbiome has even been associated with
      oncogenic pathways and under circumstances might promote the development of
      hepatocarcinogenesis. Lately, the existence of the oral-gut-liver axis has been
      related with the development of decompensating events. This link between the
      liver and the oral cavity could be via the gut through impaired intestinal
      permeability that allows direct translocation of bacteria from the oral cavity to
      the systemic circulation. Overall, the contribution of the microbiome to
      pathogenesis becomes more pronounced with progressive disease and therefore may
      represent an important therapeutic target in the management of cirrhosis.

PMID- 30228777
TI  - Implication of neurohormonal-coupled mechanisms of gastric emptying and
      pancreatic secretory function in diabetic gastroparesis.
AB  - Recently, diabetic gastroparesis (DGP) has received much attention as its
      prevalence is increasing in a dramatic fashion and management of patients with
      DGP represents a challenge in the clinical practice due to the limited
      therapeutic options. DGP highlights an interrelationship between the gastric
      emptying and pancreatic secretory function that regulate a wide range of
      digestive and metabolic functions, respectively. It well documented that both
      gastric emptying and pancreatic secretion are under delicate control by multiple
      neurohormonal mechanisms including extrinsic parasympathetic pathways and
      gastrointestinal (GI) hormones. Interestingly, the latter released in response to
      various determinants that related to the rate and quality of gastric emptying.
      Others and we have provided strong evidence that the central autonomic nuclei
      send a dual output (excitatory and inhibitory) to the stomach and the pancreas in
      response to a variety of hormonal signals from the abdominal viscera. Most of
      these hormones released upon gastric emptying to provide feedback, and control
      this process and simultaneously regulate pancreatic secretion and postprandial
      glycemia. These findings emphasize an important link between gastric emptying and
      pancreatic secretion and its role in maintaining homeostatic processes within the
      GI tract. The present review deals with the neurohormonal-coupled mechanisms of
      gastric emptying and pancreatic secretory function that implicated in DGP and
      this provides new insights in our understanding of the pathophysiology of DGP.
      This also enhances the process of identifying potential therapeutic targets to
      treat DGP and limit the complications of current management practices.

PMID- 30228779
TI  - Role of two-dimensional shear wave elastography in chronic liver diseases: A
      narrative review.
AB  - Liver biopsy is the gold standard for evaluating the degree of liver fibrosis in
      patients with chronic liver disease. However, due to the many limitations of
      liver biopsy, there has been much interest in the use of noninvasive techniques
      for this purpose. Among these techniques real-time two-dimensional shear wave
      elastography (2D-SWE) has the advantage of measuring tissue elasticity with the
      guidance of B-mode images. Recently, many studies have been conducted on the
      application of 2D-SWE in patients with various liver diseases, and their validity
      has been confirmed. Here, we briefly discuss the role of 2D-SWE in patients with
      chronic liver diseases, particularly aspects of the examination techniques and
      clinical applications.

PMID- 30228778
TI  - Drug resistance and new therapies in colorectal cancer.
AB  - Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell
      dissemination has taken place. Chemo- and targeted therapies provide only a
      limited increase of overall survival for these patients. The major reason for
      clinical outcome finds its origin in therapy resistance. Escape mechanisms to
      both chemo- and targeted therapy remain the main culprits. Here, we evaluate
      major resistant mechanisms and elaborate on potential new therapies. Amongst
      promising therapies is alpha-amanitin antibody-drug conjugate targeting
      hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor
      microenvironment exists and that this dictates therapeutic outcome. In addition,
      CRC displays a limited response to checkpoint inhibitors, as only a minority of
      patients with microsatellite instable high tumors is susceptible. In this review,
      we highlight new developments with clinical potentials to augment responses to
      checkpoint inhibitors.

PMID- 30228780
TI  - Delta-like ligand 4 in hepatocellular carcinoma intrinsically promotes tumour
      growth and suppresses hepatitis B virus replication.
AB  - AIM: To investigate the role of Delta-like ligand 4 (DLL4) on tumour growth in
      hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) in vivo.
      METHODS: We suppressed DLL4 expression in an HBV expressing HCC cell line,
      HepG2.2.15 and analysed the growth ability of cells as subcutaneous tumours in
      nude mice. The expression of tumour angiogenesis regulators, VEGF-A and VEGF-R2
      in tumour xenografts were examined by western blotting. The tumour proliferation
      and neovasculature were examined by immunohistochemistry. The viral replication
      and viral protein expression were measured by quantitative PCR and western
      blotting, respectively. RESULTS: Eighteen days after implantation, tumour volume
      in mice implanted with shDLL4 HepG2.2.15 was significantly smaller than in mice
      implanted with control HepG2.2.15 (P < 0.0001). The levels of angiogenesis
      regulators, VEGF-A and VEGF-R2 were significantly decreased in implanted tumours
      with suppressed DLL4 compared with the control group (P < 0.001 and P < 0.05,
      respectively). Furthermore, the suppression of DLL4 expression in tumour cells
      reduced cell proliferation and the formation of new blood vessels in tumours.
      Unexpectedly, increased viral replication was observed after suppression of DLL4
      in the tumours. CONCLUSION: This study demonstrates that DLL4 is important in
      regulating the tumour growth of HBV-associated HCC as well as the
      neovascularization and suppression of HBV replication.

PMID- 30228781
TI  - Optimal immunosuppressor induces stable gut microbiota after liver
      transplantation.
AB  - AIM: To study the influence of different doses of tacrolimus (FK506) on gut
      microbiota after liver transplantation (LT) in rats. METHODS: Specific pathogen
      free Brown Norway (BN) rats and Lewis rats were separated into five groups: (1)
      Tolerance group (BN-BN LT, n = 8); (2) rejection group (Lewis-BN LT, n = 8); (3)
      high dosage FK506 (FK506-H) group (Lewis-BN LT, n = 8); (4) middle dosage FK506
      (FK506-M) group (Lewis-BN LT, n = 8); and (5) low dosage FK506 (FK506-L) group
      (Lewis-BN LT, n = 8). FK506 was administered to recipients at a dose of 1.0
      mg/kg, 0.5 mg/kg, and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,
      FK506-M, and FK506-L groups, respectively. On the 30th day after LT, all rats
      were sampled and euthanized. Blood samples were harvested for liver function and
      plasma endotoxin testing. Hepatic graft and ileocecal tissues were collected for
      histopathology observation. Ileocecal contents were used for DNA extraction, Real
      time quantitative polymerase chain reaction (RT-PCR) and digital processing of
      denaturing gradient gel electrophoresis (DGGE) profiles and analysis. RESULTS:
      Compared to the FK506-H and FK506-L groups, FK506-M was optimal for maintaining
      immunosuppression and inducing normal graft function; the FK506-M maintained gut
      barrier integrity and low plasma endotoxin levels; furthermore, DGGE results
      showed that FK506-M induced stable gut microbiota. Diversity analysis indicated
      that FK506-M increased species richness and rare species abundance, and cluster
      analysis confirmed the stable gut microbiota induced by FK506-M. Phylogenetic
      tree analysis identified crucial bacteria associated with FK506-M; seven of the
      nine bacteria that were decreased corresponded to Bacteroidetes, while increased
      bacteria were of the Bifidobacterium species. FK506-M increased Faecalibacterium
      prausnitzii and Bifidobacterium spp. and decreased Bacteroides-Prevotella and
      Enterobacteriaceae, as assessed by RT-PCR, which confirmed the crucial bacterial
      alterations identified through DGGE. CONCLUSION: Compared to the low or high
      dosage of FK506, an optimal dosage of FK506 induced immunosuppression, normal
      graft function and stable gut microbiota following LT in rats. The stable gut
      microbiota presented increased probiotics and decreased potential pathogenic
      endotoxin-producing bacteria. These findings provide a novel strategy based on
      gut microbiota for immunosuppressive dosage assessment for recipients following
      LT.

PMID- 30228783
TI  - Low expression of CDK5RAP3 and DDRGK1 indicates a poor prognosis in patients with
      gastric cancer.
AB  - AIM: To investigate the effects of different levels of expression of CDK5RAP3 and
      DDRGK1 on long-term survival of patients undergoing radical gastrectomy. METHODS:
      The expression of CDK5RAP3 and DDRGK1 was detected by immunohistochemistry in 135
      patients who received standard gastrectomy were enrolled in the study. Western
      Blot was used to detect the expression of CDK5RAP3 and DDRGK1 in gastric cancer
      and its adjacent tissues and cell lines. The correlations between the expression
      of CDK5RAP3 and DDRGK1 and clinicopathological factors were analyzed, and the
      value of each parameter to the prognosis of the patients was compared. Receiver
      operating characteristic analysis was used to compare the accuracy of the
      prediction of clinical outcome by the parameters. RESULTS: CDK5RAP3 and DDRGK1
      expression was down-regulated in the gastric cancer compared to its respective
      adjacent non-tumor tissues. The expression of CDK5RAP3 was closely related to the
      age of the patients (P = 0.035) and the T stage of the tumor (P = 0.017). The
      expression of DDRGK1 was correlated with the sex of the patients (P = 0.080), the
      degree of tumor differentiation (P = 0.036), the histological type (P = 0.036)
      and the N stage of the tumor (P = 0.014). Low expression CDK5RAP3 or DDRGK1 is a
      poor prognostic factor for gastric cancer patients. Prognostic analysis showed
      that the co-expression of CDK5RAP3 and DDRGK1 was an independent prognostic
      factor correlating with the overall survival of gastric cancer patients. Combined
      expression analysis of CDK5RAP3 and DDRGK1 may provide a more accurate prognostic
      value for overall survival. CONCLUSION: The co-expression of CDK5RAP3 and DDRGK1
      is an independent prognostic factor for gastric cancer, which can provide a more
      accurate model for the long-term prognosis.

PMID- 30228782
TI  - Formin-like 3 regulates RhoC/FAK pathway and actin assembly to promote cell
      invasion in colorectal carcinoma.
AB  - AIM: To clarify the underlying mechanism of formin-like 3 (FMNL3) in the
      promotion of colorectal carcinoma (CRC) cell invasion. METHODS: The in vitro
      biological function analyses of FMNL3 were performed by gain- and loss-of
      function approaches. Changes in the F-actin cytoskeleton were detected by the
      technologies of phalloidin-TRITC labeling and confocal microscopy. The signaling
      pathway mediated by FMNL3 was explored by western blot, gelatin zymograph assay,
      co-immunoprecipitation (co-IP), immunofluorescence co-localization, and
      glutathione S-transferase (GST) pull-down assay. RESULTS: The in vitro
      experimental results showed that FMNL3 significantly promoted the proliferation,
      invasion, and migration of CRC cells (P < 0.05 and P < 0.01). Moreover, FMNL3
      regulated the remodeling of actin-based protrusions such as filopodia and
      lamellipodia in a RhoC-dependent manner. The western blot and gelatin zymograph
      assay results indicated that FMNL3 was involved in the RhoC/ focal adhesion
      kinase (FAK) pathway and acted as an effector of RhoC to activate the downstream
      signaling of p-FAK as well as p-MAPK and p-AKT. This resulted in the increased
      expression of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9
      (MMP9) and vascular endothelial growth factor (VEGF), and the subsequent
      promotion of CRC cell invasion. The results of TAE226, U0126 or Ly294002
      treatment confirmed an essential role of FMNL3 in activation of the RhoC/FAK
      pathway and the subsequent promotion of CRC invasion. Co-IP, co-localization and
      GST pull-down assays showed the direct interaction of FMNL3 with RhoC in vivo and
      in vitro. CONCLUSION: FMNL3 regulates the RhoC/FAK signaling pathway and RhoC
      dependent remodeling of actin-based protrusions to promote CRC invasion.

PMID- 30228784
TI  - Gastroduodenal ulcer bleeding in elderly patients on low dose aspirin therapy.
AB  - AIM: To determine the clinical characteristics of elderly patients of hemorrhagic
      gastroduodenal ulcer on low-dose aspirin (LDA) therapy. METHODS: A total of 1105
      patients with hemorrhagic gastroduodenal ulcer treated in our hospital between
      January 2000 and March 2016 were grouped by age and drugs used, and these groups
      were compared in several factors. These groups were compared in terms of length
      of hospital stay, presence/absence of hemoglobin (Hb) decrease, presence/absence
      of blood transfusion, Forrest I, percentage of Helicobacter pylori infection,
      presence/absence of underlying disease, and percentage of severe cases. RESULTS:
      The percentage of blood transfusion (62.6% vs 47.7 %, P < 0.001), Hb decrease
      (53.8% vs 40.8%, P < 0.001), and the length of hospital stay (23.5 d vs 16.7 d, P
      < 0.001) were significantly greater in those on drug therapy. The percentage of
      blood transfusion (65.3% vs 47.8%, P < 0.001), Hb decrease (54.2% vs 42.1%, P <
      0.001), and length of hospital stay (23.3 d vs 17.5 d, P < 0.001) were
      significantly greater in the elderly. In comparison with the LDA monotherapy
      group, the percentage of severe cases was significantly higher in the LDA
      combination therapy group when elderly patients were concerned (16.1% vs 34.0%, P
      = 0.030). Meanwhile, among those on LDA monotherapy, there was no significant
      difference between elderly and non-elderly (16.1% vs 16.0%, P = 0.985).
      CONCLUSION: A combination of LDA with antithrombotic drugs or non-steroidal anti
      inflammatory drugs (NSAIDs) contributes to aggravation. And advanced age is not
      an aggravating factor when LDA monotherapy is used.

PMID- 30228785
TI  - Predicting the presence of adenomatous polyps during colonoscopy with National
      Cancer Institute Colorectal Cancer Risk-Assessment Tool.
AB  - AIM: To evaluate the National Cancer Institute (NCI) Colorectal Cancer (CRC) Risk
      Assessment Tool as a predictor for the presence of adenomatous polyps (AP) found
      during screening or surveillance colonoscopy. METHODS: This is a retrospective
      single center observational study. We collected data of adenomatous polyps in
      each colonoscopy and then evaluated the lifetime CRC risk. We calculated the AP
      prevalence across risk score quintiles, odds ratios of the prevalence of AP
      across risk score quintiles, area under curves (AUCs) and Youden's indexes to
      assess the optimal risk score cut off value for AP prevalence status. RESULTS:
      The prevalence of AP gradually increased throughout the five risk score
      quintiles: i.e., 27.63% in the first and 51.35% in the fifth quintile. The odd
      ratios of AP prevalence in the fifth quintile compared to the first and second
      quintile were 2.76 [confidence interval (CI): 1.71-4.47] and 2.09 (CI: 1.32
      3.30). The AUC for all patients was 0.62 (CI: 0.58-0.66). Youden's Index
      indicated the optimal risk score cutoff value discriminating AP prevalence status
      was 3.60. CONCLUSION: Patients with the higher NCI risk score have higher risk of
      AP and subsequent CRC; therefore, measures to increase the effectiveness of CRC
      detection in these patients include longer withdrawal time, early surveillance
      colonoscopy, and choosing flexible colonoscopy over other CRC screening
      modalities.

PMID- 30228789
TI  - ?

PMID- 30228786
TI  - Epidemiology of viral hepatitis in Somalia: Systematic review and meta-analysis
      study.
AB  - AIM: To provide a clear understanding of viral hepatitis epidemiology and their
      clinical burdens in Somalia. METHODS: A systematic review and meta-analysis was
      conducted as Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. A comprehensive literature search of published studies on viral
      hepatitis was performed from 1977-2016 in PubMed, Google Scholar, Science Direct,
      World Health Organization African Index Medicus and the Africa Journals Online
      databases, as well as on the Ministry of Health website. We also captured
      unpublished articles that were not available on online systems. RESULTS: Twenty
      nine studies from Somalia and Somali immigrants (United Kingdom, United States,
      Italy, Libya) with a combined sample size for each type of viral hepatitis
      [hepatitis A virus (HAV): 1564, hepatitis B virus (HBV): 8756, hepatitis C virus
      (HCV): 6257, hepatitis D virus (HDV): 375 and hepatitis E virus (HEV): 278] were
      analyzed. The overall pooled prevalence rate of HAV was 90.2% (95%CI: 77.8% to
      96%). The HAV prevalence among different age groups was as follows: < 1 year old,
      61.54% (95%CI: 40.14% to 79.24%); 1-10 years old, 91.91% (95%CI: 87.76% to
      94.73%); 11-19 years old, 96.31% (95%CI: 92.84% to 98.14%); 20-39 years old,
      91.3% (95%CI: 83.07% to 95.73%); and > 40 years old, 86.96% (95%CI: 75.68% to
      93.47%). The overall pooled prevalence of HBV was 18.9% (95%CI: 14% to 29%). The
      overall pooled prevalence among subgroups of HBV was 20.5% (95%CI: 5.1% to 55.4%)
      in pregnant women; 5.7% (95%CI: 2.7% to 11.5%) in children; 39.2% (95%CI: 33.4%
      to 45.4%) in patients with chronic liver disease, including hepatocellular
      carcinoma (HCC); 7.7% (95%CI: 4.2% to 13.6%), 12.4% (95%CI: 6.3% to 23.0%) and
      11.8% (95%CI: 5.3% to 24.5%) in age groups < 20 years old, 20-39 years old and >
      40 years old, respectively. The HBV prevalence among risk groups was 20% (95%CI:
      7.19% to 44.64%) in female prostitutes, 21.28% (95%CI: 7.15% to 48.69%) in
      hospitalized adults, 5.56% (95%CI: 0.99% to 25.62%) in hospitalized children, 60%
      (95%CI: 31.66% to 82.92%) in patients with acute hepatitis, 33.55% (95%CI: 14.44%
      to 60.16%) in patients with ancylostomiasis, 12.34% (95%CI: 7.24% to 20.26%) in
      patients with leprosy and 20.19% (95%CI: 11.28% to 33.49%) in schistosomiasis
      patients. The overall pooled prevalence of HCV was estimated as 4.84% (95%CI:
      3.02% to 7.67%). The prevalence rates among blood donors, risk groups, children
      and patients chronic liver disease (including HCC) was 0.87% (95%CI: 0.33% to
      2.30%), 2.43% (95%CI: 1.21% to 4.8%), 1.37% (95%CI: 0.76% to 2.46%) and 29.82%
      (95%CI: 15.84% to 48.98%), respectively. The prevalence among genotypes of HCV
      was 21.9% (95%CI: 15.36% to 30.23%) in genotype 1, 0.87% (95%CI: 0.12% to 5.9%)
      in genotype 2, 25.21% (95%CI: 18.23% to 33.77%) in genotype 3, 46.24% (95%CI:
      37.48% to 55.25%) in genotype 4, 2.52% (95%CI: 0.82% to 7.53%) in genotype 5, and
      1.19% (95%CI: 0.07% to 16.38%) in genotype 6. The overall pooled prevalence of
      HDV was 28.99% (95%CI: 16.38% to 45.96%). The HDV prevalence rate among patients
      with chronic liver disease, including HCC, was 43.77% (95%CI: 35.09% to 52.84%).
      The overall pooled prevalence of HEV was 46.86% (95%CI: 5.31% to 93.28%).
      CONCLUSION: Our study demonstrates a high prevalence of all forms of viral
      hepatitis in Somalia and it also indicates that chronic HBV was the commonest
      cause of chronic liver disease. This highlights needs for urgent public health
      interventions and strategic policy directions to controlling the burden of the
      disease.

PMID- 30228788
TI  - Comparison of the application of treatment Panel III and American College of
      Cardiology/American heart Association guidelines for blood cholesterol treatment
      in Saudi Arabia.
AB  - Background: One of the major risk factors for cardiovascular diseases is
      hyperlipidemia. The primary aim of this study was to estimate the proportion of
      individuals between 40-75 years old that would be eligible for statin therapy
      based on ACC/AHA guideline as compared to ATP-III guideline in a population of
      patients in Saudi Arabia. We also intended to extrapolate the results to the
      entire Saudi population, and estimate the cost implications of the ACC/AHA
      treatment guideline. Methods: This study was a retrospective, observational study
      involving adult patients aged between 40-75 years old. The study was conducted at
      the primary health care clinics at King Abdul-Aziz Medical/Riyadh. The
      eligibility for statins use was assessed and compared for each patient based on
      both the recent 2013 ACC-AHA guideline and the 2002 ATP-III guideline. The cost
      implication of applying the ACC/AHA treatment guideline was estimated based on
      the average cost for 40 mg Atorvastatin in the Saudi Market. Results: A total of
      1005 patients were included in the study. Using the ATP-III guideline, there were
      139 male (43.7%) and 279 female (40.6%) eligible to receive statin therapy. Based
      on the 2013 ACC/AHA guideline, treatment is recommended in 315 males (99.1%) and
      564 females (82.1%). On the other hand, high-intensity statin was recommended in
      302 male (95%) and 400 female (58.2%). Only 74 (10.5%) patients were prescribed
      high-intensity statin of the 702 eligible patients. Extrapolating the results to
      the entire Saudi population, 2.369 million additional patients would be eligible
      for statin therapy when applying the ACC/AHA guideline. Applying the new
      guideline would result in a cost increase of at least 4.318 billion SR per year.
      Conclusions: The eligibility for statin therapy was much higher when applying the
      ACC/AHA guideline as compared to ATP-III guideline. Applying the recent ACC/AHA
      dyslipidemia guideline increased the number of patients eligible for statin
      therapy to approximately two folds. This would be associated with a substantial
      increase in cost and possibly side effects. The concerns surrounding the ACC/AHA
      guideline should be addressed at the national level.

PMID- 30228787
TI  - Unicentric Castleman disease presenting as a retroperitoneal peripancreatic mass:
      A report of two cases and review of literature.
AB  - Castleman disease (CD) is a rare disorder of lymph nodes and related tissues. CD
      generally occurs in the mediastinum, as well as in cervical, retroperitoneal and
      axillary regions. The disease is classified into two major types: unicentric CD
      (UCD) and multicentric CD. The occurrence of UCD in the retroperitoneal
      peripancreatic region is quite rare. We encountered two cases of retroperitoneal
      peripancreatic UCD in our hospital during the past three years. Following a
      series of medical examinations, including magnetic resonance imaging, computed
      tomography, ultrasonography and postoperative histopathological examination,
      these two patients were diagnosed with UCD, which presented as a retroperitoneal
      peripancreatic mass. The mass in each patient was completely excised, and no
      postoperative radiochemotherapy was administered. Both patients recovered well
      without recurrence during a follow-up period of 30 mo and 8 mo.

PMID- 30228790
TI  - Acetic Acid Bacteria in the Food Industry: Systematics, Characteristics and
      Applications.
AB  - The group of Gram-negative bacteria capable of oxidising ethanol to acetic acid
      is called acetic acid bacteria (AAB). They are widespread in nature and play an
      important role in the production of food and beverages, such as vinegar and
      kombucha. The ability to oxidise ethanol to acetic acid also allows the unwanted
      growth of AAB in other fermented beverages, such as wine, cider, beer and
      functional and soft beverages, causing an undesirable sour taste. These bacteria
      are also used in the production of other metabolic products, for example,
      gluconic acid, l-sorbose and bacterial cellulose, with potential applications in
      the food and biomedical industries. The classification of AAB into distinct
      genera has undergone several modifications over the last years, based on
      morphological, physiological and genetic characteristics. Therefore, this review
      focuses on the history of taxonomy, biochemical aspects and methods of isolation,
      identification and quantification of AAB, mainly related to those with important
      biotechnological applications.

PMID- 30228791
TI  - Recent Trends in Biodiesel and Biogas Production.
AB  - Biodiesel and biogas are two very important sources of renewable energy
      worldwide, and particularly in the EU countries. While biodiesel is almost
      exclusively used as transportation fuel, biogas is mostly used for production of
      electricity and heat. The application of more sophisticated purification
      techniques in production of pure biomethane from biogas allows its delivery to
      natural gas grid and its subsequent use as transportation fuel. While biogas is
      produced mostly from waste materials (landfills, manure, sludge from wastewater
      treatment, agricultural waste), biodiesel in the EU is mostly produced from
      rapeseed or other oil crops that are used as food, which raises the 'food or
      fuel' concerns. To mitigate this problem, considerable efforts have been made to
      use non-food feedstock for biodiesel production. These include all kinds of waste
      oils and fats, but recently more attention has been devoted to production of
      microbial oils by cultivation of microorganisms that are able to accumulate high
      amounts of lipids in their biomass. Promising candidates for microbial lipid
      production can be found among different strains of filamentous fungi, yeast,
      bacteria and microalgae. Feedstocks of interest are agricultural waste rich in
      carbohydrates as well as different lignocellulosic raw materials where some
      technical issues have to be resolved. In this work, recovery and purification of
      biodiesel and biogas are also considered.

PMID- 30228794
TI  - Production of Arachidonic Acid and Eicosapentaenoic Acid by Mortierella alpina
      CBS 528.72 on Date Waste.
AB  - Arachidonic acid (ARA) and eicosapentaenoic acid (EPA) are important for human
      health and are produced by the fungus Mortierella alpina. Fermentation conditions
      may affect fatty acid profile of produced oil. Substrates in solid-state
      fermentation are usually renewable and low-cost agro-industrial waste. The aim of
      this research is to study simultaneous production of ARA and EPA by M. alpina CBS
      528.72 in solid-state fermentation. Date waste and soybean meal served as carbon
      and nitrogen sources, respectively. Plackett-Burman design was used to evaluate
      the impact of eleven process variables on ARA and EPA production. Analysis of the
      results showed that the main variables with significant impact on production
      include seed age, and supplementation of linseed oil and nitrogen. These three
      variables were then studied in a central composite design for the optimization of
      production of both fatty acids. Finally, reconfirmation test was conducted to
      obtain experimental results from predicted optimum conditions. This report showed
      that simultaneous optimization of the production of ARA and EPA by M. alpina CBS
      528.72 on date waste can be achieved by modification of process variables in
      solid-state fermentation.

PMID- 30228793
TI  - Enzymatic Conversion of Sugar Beet Pulp: A Comparison of Simultaneous
      Saccharification and Fermentation and Separate Hydrolysis and Fermentation for
      Lactic Acid Production.
AB  - This study compares the efficiency of lactic acid production by separate
      hydrolysis and fermentation (SHF) or simultaneous saccharification and
      fermentation (SSF) of sugar beet pulp, a byproduct of industrial sugar
      production. In experiments, sugar beet pulp was hydrolyzed using five commercial
      enzymes. A series of shake flask fermentations were conducted using five selected
      strains of lactic acid bacteria (LAB). The differences in the activities of the
      enzymes for degrading the principal sugar beet pulp components were reflected in
      the different yields of total reducing sugars. The highest yields after
      hydrolysis and the lowest quantities of insoluble residues were obtained using a
      mixture (1:1) of Viscozyme(r) and Ultraflo(r) Max. In the SHF process, only a
      portion of the soluble sugars released by the enzymes from the sugar beet pulp
      was assimilated by the LAB strains. In SSF, low enzyme loads led to reduction in
      the efficiency of sugar accumulation. The risk of carbon catabolic repression was
      reduced. Our results suggest that SSF has advantages over SHF, including lower
      processing costs and higher productivity. Lactic acid yield in SSF mode (approx.
      30 g/L) was 80-90% higher than that in SHF.

PMID- 30228792
TI  - Review of Second Generation Bioethanol Production from Residual Biomass.
AB  - In the context of climate change and the depletion of fossil fuels, there is a
      great need for alternatives to petroleum in the transport sector. This review
      provides an overview of the production of second generation bioethanol, which is
      distinguished from the first generation and subsequent generations of biofuels by
      its use of lignocellulosic biomass as raw material. The structural components of
      the lignocellulosic biomass such as cellulose, hemicellulose and lignin, are
      presented along with technological unit steps including pretreatment, enzymatic
      hydrolysis, fermentation, distillation and dehydration. The purpose of the
      pretreatment step is to increase the surface area of carbohydrate available for
      enzymatic saccharification, while minimizing the content of inhibitors.
      Performing the enzymatic hydrolysis releases fermentable sugars, which are
      converted by microbial catalysts into ethanol. The hydrolysates obtained after
      the pretreatment and enzymatic hydrolysis contain a wide spectrum of sugars,
      predominantly glucose and xylose. Genetically engineered microorganisms are
      therefore needed to carry out co-fermentation. The excess of harmful inhibitors
      in the hydrolysate, such as weak organic acids, furan derivatives and phenol
      components, can be removed by detoxification before fermentation. Effective
      saccharification further requires using exogenous hemicellulases and cellulolytic
      enzymes. Conventional species of distiller's yeast are unable to ferment pentoses
      into ethanol, and only a very few natural microorganisms, including yeast species
      like Candida shehatae, Pichia (Scheffersomyces) stipitis, and Pachysolen
      tannophilus, metabolize xylose to ethanol. Enzymatic hydrolysis and fermentation
      can be performed in a number of ways: by separate saccharification and
      fermentation, simultaneous saccharification and fermentation or consolidated
      bioprocessing. Pentose-fermenting microorganisms can be obtained through genetic
      engineering, by introducing xylose-encoding genes into metabolism of a selected
      microorganism to optimize its use of xylose accumulated in the hydrolysate.

PMID- 30228795
TI  - Properties and Fermentation Activity of Industrial Yeasts Saccharomyces
      cerevisiae, S. uvarum, Candida utilis and Kluyveromyces marxianus Exposed to
      AFB1, OTA and ZEA.
AB  - In this paper the effect of aflatoxin B1, ochratoxin A and zearalenon on
      morphology, growth parameters and metabolic activity of yeasts Saccharomyces
      cerevisiae, Saccharomyces uvarum, Candida utilis and Kluyveromyces marxianus was
      determined. The results showed that the three mycotoxins affected the morphology
      of all these yeasts, primarily the cell diameter, but not their final cell count.
      Fourier transform infrared spectroscopy showed that the yeast membranes bound the
      mycotoxins, C. utilis in particular. The cell membranes of most yeasts underwent
      denaturation, except S. uvarum exposed to ochratoxin A and zearalenone. In the
      early stage of fermentation, all mycotoxin-exposed yeasts had lower metabolic
      activity and biomass growth than controls, but fermentation products and biomass
      concentrations reached the control levels by the end of the fermentation, except
      for C. utilis exposed to 20 ug/mL of zearalenone. The adaptive response to
      mycotoxins suggests that certain yeasts could be used to control mycotoxin
      concentrations in the production of fermented food and beverages.

PMID- 30228796
TI  - Performance of a Two-Stage Membrane System for Bromelain Separation from
      Pineapple Waste Mixture as Impacted by Enzymatic Pretreatment and Diafiltration.
AB  - Membrane technology has been successfully applied for the purification of
      bromelain, a protease enzyme from pineapple. However, the current system operates
      less optimally in terms of flux and separation primarily due to properties of the
      feed, such as viscosity. Hence, in this study, enzymatic pretreatment and
      diafiltration operation were employed in a two-stage ultrafiltration (UF) system
      to enhance the performance of the purification and concentration process of
      bromelain enzyme from an extract of pineapple crude waste mixture (CWM).
      Pretreatment of the CWM extract using either pectinase or cellulase, or the
      combination of both, was applied and compared regarding the apparent viscosity
      reduction. Diafiltration step was introduced in UF stage 2 and observations on
      the flux performance, enzyme recovery and enzyme purity were made. A 12% apparent
      viscosity reduction was achieved when the CWM extract was pretreated with
      pectinase which led to 37-38% improvement in the flux performance of both UF
      stages, as well as higher enzyme recovery in UF stage 1. The introduction of
      diafiltration mode in UF stage 2 managed to sustain high flux values while
      yielding 4.4-fold enzyme purity (higher than a 2.5-fold purity achieved in our
      previous work); however, high diluent consumption was needed. The outcomes of
      this study showed that the flux performance and bromelain separation can be
      enhanced by reducing the viscosity with the employment of enzymatic pretreatment
      and diafiltration operation. Thus, both techniques can be potentially applied in
      a large-scale membrane-based process for bromelain production.

PMID- 30228797
TI  - Cloning and Characterization of Limonoid Glucosyltransferase from Kinnow Mandarin
      (Citrus reticulata Blanco).
AB  - Kinnow mandarin (Citrus reticulata Blanco) is a popular citrus crop of
      northwestern India and it occupies maximum fruit area in Punjab. However, citrus
      juice processing industry is still suffering from delayed bitterness problem
      caused mainly by limonoid aglycones such as limonin. In order to study citrus
      limonoid metabolism, limonoid glucosyltransferase (LGT) gene, which encodes a
      natural debittering enzyme, was isolated from the fruit tissues of Kinnow
      mandarin. After confirmation and characterization, its full-length gene sequence
      (1533 bp) was submitted to National Centre for Biotechnology Information. Citrus
      reticulata limonoid glucosyltransferase (CrLGT) occupies a position on an
      independent branch in the largest subgroup and is phylogenetically different from
      those in other mandarin species like C. unshiu, showing its uniqueness in several
      features. The transcript expression of CrLGT, evaluated in different tissues such
      as young leaf, flavedo, albedo, sac covering and seed of Kinnow mandarin during
      early (90 days after flowering (DAF)), mid (150-210 DAF) and late (240 DAF) fruit
      developmental stages using semi-quantitative method, showed the highest
      expression in flavedo. Thus, it was concluded that the isolated LGT gene has an
      effect on limonoid metabolic engineering in citrus. Overexpression of this gene
      can reduce the delayed bitterness problem in citrus juice and enhance the
      accumulation of specific glucosides that have anticancer effects.

PMID- 30228798
TI  - Effect of Season, Location, Filleting Regime and Storage on Water-Holding
      Properties of Farmed Atlantic Salmon (Salmo salar L.).
AB  - The effect of season, localization, filleting regime and storage on water-holding
      properties of Atlantic salmon (Salmo salar L.) was investigated. Salmon was
      sampled at two different slaughter facilities (in the north and south of Norway)
      in autumn and spring and divided in pre- and post-rigor groups, which were
      sampled before and after filleting. This gave a total of 16 groups that were
      analyzed for water-holding capacity (WHC), water content and pH. In addition, a
      storage trial was performed to assess the effect of all the design variables on
      drip loss and the composition of the drip loss during up to 18 days of storage.
      WHC was significantly affected by both rigor status and filleting, while water
      content was affected by localization and filleting. In addition, post-rigor
      filleting gave significantly decreased drip loss compared to pre-rigor filleting.
      However, storage time had the highest impact on the drip loss. Based on this, it
      is concluded that pre-rigor filleted salmon have excellent water-holding
      properties and a great potential for early processing (pre-rigor processing). It
      was however difficult to find a clear connection between the drip loss and the
      water-holding capacity of the muscle.

PMID- 30228799
TI  - The Tunisian Artemisia Essential Oil for Reducing Contamination of Stored Cereals
      by Tribolium castaneum.
AB  - Essential oils of three species of Artemisia genus (A. absinthium L., A.
      campestris L. and A. herba-alba (Asso)) were analyzed by gas chromatography-mass
      spectrometry (GC-MS) and their potential insecticidal and repellent activities
      against the stored grain insect Tribolium castaneum (Herbst) was investigated.
      Fumigant and repellent activity bioassays were investigated in vitro. Chemical
      characterisation of essential oils showed that the bicyclic monoterpenes were
      predominant in all Artemisia essential oils, A. absinthium essential oil having
      the highest content of bicyclic monoterpenes, bicycloheptanes, naphthalenes and
      cycloalkenes. A. campestris had the highest content of sesquiterpenoids and
      acyclic monoterpenoids. A. herba-alba was characterised by the highest amounts of
      menthane monoterpenoids, oxanes, cumenes, oxolanes, ketones, benzenoids and
      monocyclic monoterpenes. Fumigant bioassay demonstrated that the three types of
      oil applied separately caused significant insect mortality. The lowest median
      lethal dose, LC50=142.8 MUL/L, was observed with A. herba-alba. In repellency
      test, essential oil of A. absinthium was more potent with more rapid action than
      all other species. The mixture of Artemisia sp. essential oils showed an
      antagonistic effect in all the tested combinations. This study highlighted an
      important potential of Artemisia sp. especially A. herba-alba and A. absinthium
      in the control of the pests of stored products.

PMID- 30228800
TI  - Effect of Fermentation on the Protein Digestibility and Levels of Non-Nutritive
      Compounds of Pea Protein Concentrate.
AB  - In order to determine the impact of fermentation on protein quality, pea protein
      concentrate (PPC) was fermented with Lactobacillus plantarum for 11 h and total
      phenol and tannin contents, protease inhibitor activity, amino acid composition
      and in vitro protein digestibility were analyzed. Phenol levels, expressed as
      catechin equivalents (CE), increased on dry mass basis from 2.5 at 0 h to 4.9 mg
      CE per 1 g of PPC at 11 h. Tannin content rose from 0.14 at 0 h to a maximum of
      0.96 mg CE per 1 g of PPC after 5 h, and thereafter declined to 0.79 mg/g after
      11 h. After 9 h of fermentation trypsin inhibitor activity decreased, however, at
      all other fermentation times similar levels to the PPC at time 0 h were produced.
      Chymotrypsin inhibitor activity decreased from 3.7 to 1.1 chymotrypsin inhibitory
      units (CIU) per mg following 11 h of fermentation. Protein digestibility reached
      a maximum (87.4%) after 5 h of fermentation, however, the sulfur amino acid score
      was reduced from 0.84 at 0 h to 0.66 at 11 h. This reduction in sulfur content
      altered the in vitro protein digestibility-corrected amino acid score from 67.0%
      at 0 h to 54.6% at 11 h. These data suggest that while fermentation is a viable
      method of reducing certain non-nutritive compounds in pea protein concentrate,
      selection of an alternative bacterium which metabolises sulfur amino acids to a
      lesser extent than L. plantarum should be considered.

PMID- 30228801
TI  - The Effect of Short-Toothed and Dalmatian?Sage Extracts on Platelet Aggregation.
AB  - Sage (Salvia sp.) is a genus of a native Mediterranean plant used for
      aromatization of foods. In this study, total polyphenolic profile, antioxidant
      properties and antiplatelet effect of short-toothed sage (Salvia brachyodon
      Vandas) are analyzed and compared to most commonly used Salvia species (S.
      officinalis, Dalmatian sage). Content of total flavonoids was 0.08-0.23% and of
      phenolic acids 0.47-3.04%. Antioxidant DPPH assay showed higher antioxidant
      capacity of S. brachyodon (29-36 mg/mL of gallic acid equivalents) than of S.
      officinalis. In functional test of primary haemostasis, extracts of S. brachyodon
      have prevented platelet aggregation in nanomolar concentration (21 nM), thus
      showing potential in prevention of thrombus formation as functional food or
      dietary supplement. Antiplatelet activity was related to antioxidant capacity
      (r=0.7014, p=0.0352) indicating that prevention of aggregation is not caused by
      an individual component, but it is rather a result of synergistic effect of
      polyphenols. The obtained results are preliminary and a more detailed study of
      the possibility of applying the investigated plant species as supplements for the
      prevention of the problem of cardiovascular system and platelet aggregation is
      needed.

PMID- 30228802
TI  - Bioprospecting for Genes Encoding Hydrocarbon-Degrading Enzymes from Metagenomic
      Samples Isolated from ?Northern Adriatic Sea Sediments.
AB  - Three metagenomic libraries were constructed using surface sediment samples from
      the northern Adriatic Sea. Two of the samples were taken from a highly polluted
      and an unpolluted site respectively. The third sample from a polluted site had
      been enriched using crude oil. The results of the metagenome analyses were
      incorporated in the REDPET relational database
      (http://redpet.bioinfo.pbf.hr/REDPET), which was generated using the previously
      developed MEGGASENSE platform. The database includes taxonomic data to allow the
      assessment of the biodiversity of metagenomic libraries and a general functional
      analysis of genes using hidden Markov model (HMM) profiles based on the KEGG
      database. A set of 22 specialised HMM profiles was developed to detect putative
      genes for hydrocarbon-degrading enzymes. Use of these profiles showed that the
      metagenomic library generated after selection on crude oil had enriched genes for
      aerobic n-alkane degradation. The use of this system for bioprospecting was
      exemplified using potential alkB and almA genes from this library.

PMID- 30228804
TI  - Soil Microbial Community Structure and Diversity around the Aging Oil Sludge in
      Yellow River Delta as Determined by High-Throughput Sequencing.
AB  - Microorganisms are sensitive indicators of edaphic environmental variation. The
      Illumina MiSeq sequencing technology was used to analyze soil bacterial community
      diversity around an aging oil sludge in the Yellow River Delta. The alpha
      diversity index of soil bacterial community results (Ace, Chao, Shannon, and
      Simpson) determined that bacterial community diversity sampling within the scope
      of a 20 cm radius from the center of an aging oil sludge spot showed the most
      abundant diversity. The level of diversity distributed symmetrically with radial
      direction from the center of the aging oil sludge spot. Over the distance of 100
      m from the center, bacterial community diversity tends to be monotonous, with
      small differences especially in the horizontal direction underground. The alpha
      diversity indicators also showed that the bacterial diversity of samples were
      close under the aging oil sludge. In addition, the aging oil sludge inhibited the
      growth of bacteria compared with the referenced unpolluted soil sample and also
      increased the diversities of soil bacteria. At the phylum level, the
      Proteobacteria, Chloroflexi, and Actinobacteria existing in the aging oil sludge
      contaminated wetland soil constituted a larger proportion of the community, while
      the proportion of Firmicute was relatively less. On the contrary, Firmicute
      showed the highest content of 63.8% in the referenced soil. Under the genus level
      and family level, the corresponding strains that resisted the aging oil sludge
      were selected. According to the bacterial diversity analysis, the basic structure
      of the bacterial community which could be used for remediation of aging oil
      sludge-contaminated soil was also developed.

PMID- 30228803
TI  - Time-Kill Kinetics of Lipid Fractions Isolated from Condiments against Foodborne
      Pathogens.
AB  - Lipid fractions that are extracted from condiments have a wide array of
      biological potential and are commonly utilized for medicinal and culinary
      applications. This investigation aims at determining the antimicrobial potential
      of lipid fractions isolated using two different solvent systems against five
      foodborne pathogens. The antibacterial efficacy was tested after 0, 1, 2, 3 and
      24 h of incubation with the active agent. The leakage of cellular content was
      assessed at 1 and 2 h of incubation. Scanning electron microscope (SEM) images
      were obtained after 18 h of contact time with lipid fractions at their minimum
      inhibitory concentration (MIC). From the results obtained from time-kill and cell
      constituents release tests, it could be concluded that during 3 and 1 h of
      incubation, the lipid fractions were more potent against Gram-negative isolates
      (Escherichia coli ATCC 8739). However, prolonged incubation with the active agent
      inhibited Gram-positive isolate, i.e. Listeria monocytogenes ATCC 13932. SEM
      images of treated microorganisms also confirmed the inhibitory action of selected
      lipid fractions against all the tested pathogens. The cellular morphology of the
      bacteria was completely altered after 18 h of incubation with the lipid
      fractions. The results of the present study corroborate significant inhibitory
      effects and disruption in bacterial cell integrity following prolonged incubation
      with these lipid fractions. The results also affirm the use of the tested lipid
      fractions in food systems.

PMID- 30228805
TI  - Influence of Spinal Manipulation on Muscle Spasticity and Manual Dexterity in
      Participants With Cerebral Palsy: Randomized Controlled Trial.
AB  - Objectives: The aim of this study was to investigate the short-term effects of
      spinal manipulation (SM) on wrist muscle spasticity and manual dexterity in
      participants with cerebral palsy (CP). Methods: After baseline examination, 78
      participants with spastic CP (7-18 years) without contractures or hyperkinetic
      syndrome were randomly allocated into 2 groups. The experimental group underwent
      SM to the cervical, thoracic, and lumbar spine, and the control group received
      sham SM. A second evaluation was performed 5 minutes postintervention. Wrist
      muscle spasticity was measured quantitatively with NeuroFlexor (Aggero MedTech
      AB, Solna, Sweden), a device assessing resistance to passive movements of
      different velocities. Between-group difference was calculated using the Mann
      Whitney U test. Manual dexterity was evaluated by the Box and Block test.
      Results: In the experimental group, muscle spasticity was reduced by 2.18 newton
      from median 5.53 with interquartile range 8.66 to median 3.35 newton with
      interquartile range 7.19; the difference was statistically significant (P =
      .002). In the control group, reduction in spasticity was negligible. The between
      group difference in change of muscle spasticity was statistically significant (P
      = .034). Improvement of manual dexterity was not statistically significant (P =
      .28). Conclusions: These findings suggest that SM may, in the short term, help to
      reduce spasticity in participants with CP. Long-term effects of SM on muscle
      spasticity have yet to be studied.

PMID- 30228807
TI  - Correlation Between Upper Body Balance, Muscle Strength, and Power in Cricketers
      Belonging to Different Age Groups.
AB  - Objective: The purpose of this study was to assess correlation between variables
      of upper body balance, muscular strength, and power in cricketers belonging to
      different age groups. Methods: Forty-eight healthy male cricketers (26
      adolescents aged 14-17 years and 22 adults aged 18-25 years) were recruited from
      Jamia Millia Islamia, New Delhi, India. After a warm-up, the participants
      underwent Upper Quarter Y Balance Test, backward overhead medicine ball throw
      test, and back-strength testing in a random order. Results: Values of the Pearson
      correlation coefficient for muscle strength and upper body power were found to be
      0.397 and 0.499 for adolescent and adult cricketers, respectively. Correlation
      coefficient values for upper body balance and strength range from -0.008 to 0.05
      and 0.325 to 0.414 and for upper body balance and power range from 0.059 to 0.062
      and 0.133 to 0.153 for adolescent and adult cricketers, respectively. Conclusion:
      Statistically significant, moderate-sized correlations were demonstrated between
      muscular strength and upper body power in adolescent and adult cricketers.
      However, no correlations existed between upper body balance and power and upper
      body balance and muscular strength in these athletes.

PMID- 30228806
TI  - Reliability of Electromyographic Assessment of Biceps Brachii and Triceps Brachii
      in Cricketers.
AB  - Objective: The purpose of this study is to determine the intraexaminer and
      interexaminer reliability of electromyographic assessment of biceps brachii (BB)
      and triceps brachii (TB) muscles in cricketers. Methods: Sixteen healthy male
      cricketers (ages 14-35 years) recruited from Jamia Millia Islamia, New Delhi,
      India were tested on 2 occasions that were held 1 week apart. On the first
      occasion, only examiner 1 performed the testing; on the second occasion, examiner
      1, examiner 2, and examiner 3 all performed testing. While testing for surface
      electromyography (sEMG) activity of BB and TB muscles, participants were asked to
      produce maximal voluntary isometric contraction (MVIC), which was to be held for
      5 seconds against the resistance provided by an examiner. Participants performed
      3 MVICs per muscle per examiner, with a rest interval of 3 minutes between
      consecutive contractions. Intraclass correlation coefficient, standard error of
      measurement, and minimum detectable change were calculated to determine the
      reliability of repeated sEMG measurements. Results: Nonsignificant differences
      were observed for the 2 trials completed by examiner 1 (paired t test) and
      testing done by all 3 examiners (repeated measures analysis of variance) at P <
      .05 for both BB and TB. Intraclass correlation coefficient values ranged from .84
      to .86 for BB and .89 to .98 for TB. Standard error of measurement (minimum
      detectable change) was .052 (.144) mV and .041 (.114) mV for BB intraexaminer and
      interexaminer reliability testing, respectively, and .018 (.051) mV and .043
      (.119) mV for TB intraexaminer and interexaminer reliability testing. Ninety-five
      percent of the mean differences between almost all of the repeated measurements
      were found to lie within the agreement intervals estimated by Bland-Altman plots.
      Conclusion: This preliminary study suggests that sEMG is a reliable tool with
      excellent intraexaminer and interexaminer reliability for assessing the activity
      of BB and TB muscles in male cricketers. These findings suggest that sEMG can be
      used to assess MVIC activity of these muscles in clinical settings, as well as in
      research area.

PMID- 30228808
TI  - Cervical Spine Assessment Using Passive and Active Mobilization Recorded Through
      an Optical Motion Capture.
AB  - Objective: The purpose of this study was to develop and measure a protocol for
      evaluation of cervical range of motion (ROM), based on passive mobilization (PM)
      combined with active mobilization (AM) and recorded through an optical motion
      capture system. Methods: Passive and active mobilization were applied to 24
      asymptomatic participants. Cervical ROM was recorded in 3 anatomic planes
      (transversal, frontal, and sagittal) using a precision optical system and a set
      of rigid bodies placed on the sacrum, spinous processes of the C7-T1 vertebrae,
      and the head. Three captures were made for each participant, distributed over 2
      days. The characteristics of the PM, the interaction with the AM, and the
      coherence patterns between tests were analyzed. Reliability was studied for these
      procedures. Results: The reliability results of the PM were high in all analyzed
      indices; only flexion showed low values. Reliability of AM was greater than PM
      for flexion, extension, and lateralization because of the similarity to rotation.
      No statistically significant differences were found comparing PM and AM
      techniques. Conclusion: The authors present a cervical ROM assessment based on
      combined PM and AM protocols at different sessions. This model demonstrated high
      reliability, individually and combined, and no differences were detected between
      PM and AM ROMs. Because the evaluator, instrumentation, and the patient are
      factors that could influence outcomes, the authors suggest that they be combined
      in protocols. These protocols could be used to evaluate the functional and
      structural capacity of patients and inform clinical outcomes.

PMID- 30228809
TI  - Effect of Foot Reflexology on Capillary Blood Glucose, Tissue Temperature, and
      Plantar Pressure of Individuals With Diabetes Mellitus (Type 2): A Pilot Study.
AB  - Objective: The purpose of this study was to assess the effect of foot reflexology
      on capillary blood glucose, feet tissue temperature, and plantar pressure of the
      feet of individuals with diabetes mellitus (type 2). Methods: Forty-five
      individuals with type 2 diabetes mellitus were stratified into 2 groups: treated
      (n = 21), which received orientation about foot self-care and received 12 foot
      reflexology sessions; and control (n = 24), which received only orientations
      about foot self-care. A portable glucose meter, an infrared thermography camera,
      and a baropodometer evaluated the variables. Results: The data indicate that,
      after 12 therapy sessions, there were no significant differences between the
      groups for producing effects on capillary blood glucose, feet tissue temperature,
      and plantar pressure. Conclusion: No significant effect was observed after 12
      foot reflexology sessions in the variables that were evaluated.

PMID- 30228810
TI  - Multimodal Therapy Combining Spinal Manipulation, Transcutaneous Electrical Nerve
      Stimulation, and Heat for Primary Dysmenorrhea: A Prospective Case Study.
AB  - Objective: The purpose of this case study was to report the effects of multimodal
      therapy as an adjunct to oral contraceptives on pain and menstrual symptoms in a
      patient with primary dysmenorrhea. Clinical Features: A 27-year old nulligravid
      and nulliparous woman presented with low back pain, thigh pain, and menstrual
      symptoms associated with primary dysmenorrhea. Multimodal therapies (spinal
      manipulation, clinic-based transcutaneous electrical nerve stimulation, and heat
      applied at home) were delivered over 3 menstrual cycles. Outcome measures
      included pain (visual analogue scale) and menstrual symptoms (Menstrual Distress
      Questionnaire) from baseline to follow-up. She continued to take her oral
      contraceptives throughout the study period. Intervention and Outcome: For both
      low back and thigh pain, the patient reported clinically important differences in
      average pain and worst pain after 2 and 3 months from baseline. There were no
      clinically important differences in current pain, best pain, or menstrual
      symptoms at follow-up. No adverse events were reported. Conclusion: Some of this
      patient's dysmenorrhea symptoms responded favorably to multimodal therapy over 5
      months. The authors observed important short-term reductions in low back and
      thigh pain (average and worst pain intensity) during care.

PMID- 30228811
TI  - Ultrasound-guided Dry Needling Treatment of Myofascial Trigger Points for
      Piriformis Syndrome Management: A Case Series.
AB  - Objective: The purpose of this case series was to describe the outcomes of
      diagnostic ultrasound-assisted dry needling in the management of piriformis
      syndrome. Clinical Features: Case 1: a 45-year-old woman reported gluteal pain
      occasionally radiating in the sciatic region. Her magnetic resonance imaging
      showing sciatic nerve edema in the underlying portion of the piriformis muscle.
      Case 2: a 55-year-old man had gluteal pain after deep palpation or being in a
      prolonged sitting position. A previous magnetic resonance imaging showed a disk
      herniation at L2-L3. Case 3: a 65-year-old woman reported pain in the sciatic
      area when she was walking and at nighttime rest. All patients had been treated
      with oral drugs, with poor results. Interventions and Outcome: Patients had the
      same quality and duration of symptoms. The treatments of piriformis muscle and
      gluteus minimus, medius, and maximus muscles were performed using a convex probe
      and a 0.30 * 60 mm needle, which was inserted out of plane, maintaining a
      constant view of its tip. All patients were treated over 10 days and followed up
      for 6 months. Their symptoms resolved during this time and no adverse reactions
      were reported. Conclusion: For these 3 patients with piriformis syndrome who were
      treated with ultrasound-guided dry-needling treatment, their symptoms resolved
      and their quality of life improved.

PMID- 30228812
TI  - Osteomyelitis of the Thumb in a 21-Year-Old Chiropractic Patient: A Case Report.
AB  - Objective: The purpose of this case report is to describe the presentation of a
      patient with osteomyelitis of the thumb. Clinical Features: A 21-year-old man
      presented with painful, red, and edematous thumb pain over the anterior and
      posterior surface for a duration of 4 days. The patient reported no trauma or
      recent operation. The patient was treated conservatively for capsulitis. The
      patient's symptoms worsened within 2 days, and he was referred for additional
      imaging consisting of a bone scan. The bone scan showed increased uptake,
      resulting in a change of diagnosis to suspected osteomyelitis. The patient was
      referred to a medical doctor for care that consisted of antibiotics and
      physiotherapy. Intervention and Outcome: Despite treatment, the patient had some
      mild permanent damage to the range of motion of the joint and soft tissue volume
      loss. Conclusion: This case demonstrates the importance of considering
      osteomyelitis as a differential diagnosis. Amputation was avoided for this
      patient because of the early recognition and referral.

PMID- 30228813
TI  - Development of a Symmetry Score for Infantile Postural and Movement Asymmetries:
      Preliminary Results of a Pilot Study.
AB  - Objective: The purpose of this study was to develop and verify a quantifiable
      symmetry score for infantile postural and movement asymmetries. Methods: Three
      studies were conducted. For reliability, 6 test items examining postural and
      movement asymmetries, which came under consideration, were investigated in 24
      infants with postural abnormality (range: 14-24 weeks). The inter-rater
      reliability was chosen as the primary endpoint. Furthermore, intrarater
      reliability and test-retest reliability were determined. Analysis and weighting
      of the items were performed by calculating the intraclass correlation
      coefficient. The validity was reviewed by expert opinion and by using a study
      with 26 infants (range: 12-28 weeks) of a cross-section population. The pilot
      study involved 38 infants, aged 14 to 24 weeks, who were examined using video.
      Their autonomic symptoms were recorded, and subsequently, they were treated once
      by means of manual medicine. The parents were instructed to a daily home program
      that focused on "tummy time." Results: The reliability tests led to a 4-item
      symmetry score with a point value between 4 points (very symmetrical) and 17
      points (very asymmetrical). The chosen items achieved an intraclass correlation
      coefficient >0.8 and Cohen's kappa >0.6, respectively. The experts' opinions
      matched mainly to a majority agreement (>50%). Furthermore, a comparison between
      the outcome of clinical testing and the symmetry score applied to 26 children
      without diagnosed abnormalities displayed an agreement of 84.6%. The pilot study
      showed a good reduction of the postural and movement abnormalities because 63% of
      the manual treated children were assessed as being symmetric afterward.
      Conclusion: The reliable and valid 4-item symmetry score served for the
      diagnosis, evaluation, and follow-up of infants aged 3 to 6 months with infantile
      postural and movement asymmetries. The results of a pilot study showed the
      positive effect of a single manual medical treatment session along with a home
      program focusing on "tummy time."

PMID- 30228814
TI  - Nonmonotonic Dose-Response Curves Occur in Dose Ranges That Are Relevant to
      Regulatory Decision-Making.
AB  - Non-monotonic dose response curves (NMDRCs) occur in cells, tissues, animals and
      human populations in response to nutrients, vitamins, pharmacological compounds,
      hormones and endocrine disrupting chemicals (EDCs). Yet, regulatory agencies have
      argued that NMDRCs are not common, are not found for adverse outcomes, and are
      not relevant for regulation of EDCs. Under the linear dose response model, high
      dose testing is used to extrapolate to lower doses that are anticipated to be
      'safe' for human exposures. NMDRCs that occur below the toxicological no-observed
      adverse-effect level (NOAEL) would falsify a fundamental assumption, that high
      dose hazards can be used to predict low dose safety. In this commentary, we
      provide examples of NMDRCs and discuss how their presence in different portions
      of the dose response curve might affect regulatory decisions. We provide evidence
      that NMDRCs do occur below the NOAEL dose, and even below the 'safe' reference
      dose, for chemicals such as resveratrol, permethrin, chlorothalonil, and
      phthalates such as DEHP. We also briefly discuss the recent CLARITY-BPA study,
      which reported mammary adenocarcinomas only in rats exposed to the lowest BPA
      dose. We conclude our commentary with suggestions for how NMDRCs should be
      acknowledged and utilized to improve regulatory toxicity testing and in the
      calculation of reference doses that are public health protective.

PMID- 30228815
TI  - SHMT2 Overexpression Predicts Poor Prognosis in Intrahepatic Cholangiocarcinoma.
AB  - Background and Objective: Serine hydroxymethyltransferase 2 (SHMT2) functions as
      a key enzyme in serine/glycine biosynthesis and one-carbon metabolism. Recent
      studies have shown that SHMT2 participated in tumor growth and progression in a
      variety of cancer types. The objective of the present study is to explore the
      expression of SHMT2 and evaluate its prognostic value in patients with
      intrahepatic cholangiocarcinoma (iCCA). Patients and Methods: We retrospectively
      investigated the expression of SHMT2 in 100 primary iCCA samples through
      immunohistochemical (IHC) staining on a tissue array. Results: High SHMT2
      expression was found in 52 of the 100 specimens. The results indicated that SHMT2
      level was upregulated compared to adjacent nontumor intrahepatic bile duct
      tissue. Furthermore, SHMT2 level was closely associated with tumor T stage (P =
      0.017) and tumor TNM stage (P = 0.041) in patients with iCCA, but not with age,
      gender, tumor size, tumor number, pathological grade, vascular invasion, or N
      stage. Moreover, Kaplan-Meier analysis suggested that patients with lower SHMT2
      level have longer survival rate than those with high expression (45.8 vs 23.1%, P
      = 0.030). Additionally, the multivariate analysis model indicated SHMT2 is an
      independent adverse prognosticator in iCCA. Conclusion: High SHMT2 level was
      correlated with poorer overall survival in patients with iCCA. SHMT2 was proved
      to be a powerful and independent prognostic factor and a potential therapeutic
      target for patients with iCCA.

PMID- 30228817
TI  - Management and Follow-up of Patients with a Bronchial Neuroendocrine Tumor in the
      Last Twenty Years in Ireland: Expected Inconsistencies and Unexpected
      Discoveries.
AB  - Bronchial neuroendocrine tumors (NET) are classified into well-differentiated
      typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine
      carcinomas (LCNEC), and small cell lung carcinomas (SCLC). We retrospectively
      reviewed and analyzed the diagnostic and therapeutic aspects, follow-up data, and
      outcomes of all patients diagnosed with a bronchial NET from 1995 to 2015 at our
      institution. Patients with LCNEC or SCLC were excluded due to the biological and
      clinical differences from the other bronchial NET. The clinical, laboratory,
      imaging, treatment, and follow-up data were collected and analyzed keeping in
      mind the recently published international recommendations. Forty-six patients
      were included in the study. Of these, 37 had a TC and 5 an AC. In 4 patients, the
      histological characterization was inadequate. Forty-four patients underwent
      surgery. Four patients developed metastatic disease. Interestingly, 14 patients
      had one or more other tumors diagnosed at some stage and 3 of them had three
      different tumors. A total of 7 patients died. The analysis of the laboratory and
      pathology assessment identified some inconsistencies when compared to the
      international recommendations. Although the treatment of bronchial NET at our
      institution was consistent with the successively published recommendations, it
      appears that the diagnostic process and the follow-up surveillance were not. We
      think that a systematic multidisciplinary approach might improve bronchial NET
      patient care. A relatively high rate of occurrence of a second, or also a third,
      non-NET tumor was observed, though the statistical value of such observation
      could not be exhaustively elucidated in this numerically limited patient
      population. In our opinion, the observed high rate of second malignancies in this
      patient cohort highlights the necessity of optimizing the follow-up of the
      bronchial NET patients, also considering the very good survival rate achieved
      with regard to the bronchial NET.

PMID- 30228816
TI  - MeHg Causes Ultrastructural Changes in Mitochondria and Autophagy in the Spinal
      Cord Cells of Chicken Embryo.
AB  - Methylmercury (MeHg) is a known neurodevelopmental toxicant, which causes changes
      in various structures of the central nervous system (CNS). However,
      ultrastructural studies of its effects on the developing CNS are still scarce.
      Here, we investigated the effect of MeHg on the ultrastructure of the cells in
      spinal cord layers. Chicken embryos at E3 were treated in ovo with 0.1 MUg
      MeHg/50 MUL saline solution and analyzed at E10. Then, we used transmission
      electron microscopy (TEM) to identify possible damage caused by MeHg to the
      structures and organelles of the spinal cord cells. After MeHg treatment, we
      observed, in the spinal cord mantle layer, a significant number of altered
      mitochondria with external membrane disruptions, crest disorganization, swelling
      in the mitochondrial matrix, and vacuole formation between the internal and
      external mitochondrial membranes. We also observed dilations in the Golgi complex
      and endoplasmic reticulum cisterns and the appearance of myelin-like cytoplasmic
      inclusions. We observed no difference in the total mitochondria number between
      the control and MeHg-treated groups. However, the MeHg-treated embryos showed an
      increased number of altered mitochondria and a decreased number of mitochondrial
      fusion profiles. Additionally, unusual mitochondrial shapes were found in MeHg
      treated embryos as well as autophagic vacuoles similar to mitophagic profiles. In
      addition, we observed autophagic vacuoles with amorphous, homogeneous, and
      electron-dense contents, similar to the autophagy. Our results showed, for the
      first time, the neurotoxic effect of MeHg on the ultrastructure of the developing
      spinal cord. Using TEM we demonstrate that changes in the endomembrane system,
      mitochondrial damage, disturbance in mitochondrial dynamics, and increase in
      mitophagy were caused by MeHg exposure.

PMID- 30228818
TI  - Ehlers-Danlos Syndrome: Not Just Joint Hypermobility.
AB  - Ehlers-Danlos syndrome is an umbrella term for a group of heritable soft
      connective tissue disorders which is characterized by joint hypermobility, skin
      texture and elasticity abnormalities, and visceral and vascular fragility or
      dysfunctions. As the syndrome is rare, it is often underdiagnosed. Patients
      usually present late, with chronic moderate to severe pain which is attributed to
      the joint hypermobility and joint subluxations. If the clinician is aware of the
      syndrome, he/she can identify affected patients in order to prevent
      complications. We report a 60-year-old woman with arthralgia and back pain
      lasting for several months and recent metatarsophalangeal luxation of the left
      toe who was discovered to have Ehlers-Danlos syndrome.

PMID- 30228819
TI  - Lamotrigine-Valproic Acid Interaction Leading to Stevens-Johnson Syndrome.
AB  - Lamotrigine (LTG) is currently indicated as adjunctive therapy for focal and
      generalized tonic-clonic seizures and for treatment of bipolar disorder and
      neuropathic pain. A common concern with LTG in children is the frequency of
      appearance of skin rash. The intensity of this adverse effect can vary from
      transient mild rash to Stevens-Johnson syndrome (SJS), which can be fatal mainly
      when LTG is coadministered with valproic acid (VPA). Hereby, we present the case
      of an 8-year-old boy who suffered from SJS and other complications two weeks
      after LTG was added to his VPA treatment in order to control his seizures. VPA is
      known to decrease LTG clearance via reduced glucuronidation. In this case, the
      minor elimination pathway of LTG would play a more important role, and the
      formation of an arene oxide metabolite would be enhanced. As this reactive
      metabolite is detoxified mainly by enzymatic reactions, involving microsomal
      epoxide hydrolase and/or GSH-S-transferases and these enzymes are polymorphically
      expressed in humans, arene oxide toxicity is increased when epoxide hydrolase or
      GSH-S-transferases is either defective or inhibited or a depletion of
      intracellular glutathione levels is taking place. VPA can cause inhibition of
      epoxide hydrolase enzymes and/or depletion of glutathione levels leading to
      adverse cutaneous reactions.

PMID- 30228821
TI  - Integrated Genome-Wide Analysis of Gene Expression and DNA Copy Number Variations
      Highlights Stem Cell-Related Pathways in Small Cell Esophageal Carcinoma.
AB  - Purpose/Objectives. Primary small cell esophageal carcinoma (SCEC) represents a
      rare and aggressive malignancy without any prospective clinical trial or
      established treatment strategy at present. Although previous studies have
      indicated similarities between SCEC and small cell lung cancer (SCLC) in terms of
      their clinical manifestations, pathology, and morphology, very little genetic
      information is available on this highly malignant tumor. At present, patients
      with SCEC are staged and treated according to the guidelines established for
      SCLC. However, early recurrence and distant metastasis are common, and long-time
      survivors are rare. Current options available for patients with relapsed SCEC are
      fairly unsatisfactory, and their prognosis is generally poor. Novel therapeutic
      approaches against SCEC are therefore urgently needed and require a deeper
      understanding of the underlying genetic mechanisms. The current investigation
      aims to characterize the gene expression profile and copy number variations
      (CNVs) in SCEC to clarify molecular markers and pathways that may possess
      clinical significance. Materials/Methods. De novo expression array was carried
      out on three matched sets of primary SCEC and adjacent normal tissue samples
      procured from the institutional tissue bank, utilizing the Affymetrix HG U133
      Plus 2.0 Array. After individual tissue normalization, the statistical software
      GeneSpring GX 12.5 was used to determine differentially expressed genes (DEGs) in
      the tumors relative to their paired normal tissues. Gene enrichments in addition
      to functional annotation and gene interaction networks were performed using DAVID
      6.8 and STRING 10.0, respectively. A gene alteration was determined to be
      recurrent if it was observed in at least 2 samples. Chromosomes X and Y were not
      included in calculations as gender differences are a known source of analysis
      bias. The DEGs of at least one SCEC sample could be mapped to the CNV regions
      (fold change (FC) >= 2 and false discovery rate (FDR) < 0.01) after gene
      expression profiling by RefSeq Transcript ID. These overlapped genes were
      subjected to the functional annotation using DAVID 6.8. In order to elucidate the
      effect of CNV on mRNA expression, we integrated the genome-wide copy number data
      and gene expression in 3 paired samples. CNV-associated gene expression
      aberration (CNV-FC) was calculated for the recurrent DEGs using previously
      published integrated microarray data as reference. Pearson's correlation
      coefficient was employed to determine if there was a statistical correlation
      between the gene expression log2 ratios and their copy numbers using the SPSS
      19.0 software. Genes that possessed CNV-FC >= 2 and r >= 0.6 (p < 0.05) were
      determined to be genes potentially associated with cancer. Results. High-quality
      DNA and total RNA were first extracted from both SCEC and normal tissues.
      Microarray data showed significant upregulation in WNT gene sets and
      downregulation in the PTEN and notch gene sets in SCEC. Functional annotation
      showed that genes associated with DNA replication, mitosis, cell cycle, DNA
      repair, telomere maintenance, RB, and p53 pathways were significantly altered in
      SCEC compared to corresponding noncancerous tissues (Benjamini p < 0.05).
      Thirteen recurrent CNVs were found in all SCEC samples by array CGH. Chromosomal
      regions with gain were located in 14q11.2, and regions with loss were located in
      4q22.3-23.3, 3q25.31-q29, 5p15.31-15.2, 8q21.11-24.3, and 9p23-13.1 in all
      samples. In two samples, the 14q11.2-32.33 region was amplified, whereas 3p26.3
      25.3, 4p16.3-11, 4q11-22.3, 4q23-25, 8p23.3, and 16p13.3 were deleted. We further
      identified 306 genes that consistently differed in copy number and expression
      (194 upregulated and 112 downregulated) between the SCEC and noncancerous tissues
      in all three samples. These genes were significantly enriched with those involved
      in cell cycle, mitosis, DNA repair, P53 pathway, and RB pathway, according to
      their functional annotation. These 306 DEGs also included network genes of the
      above pathways such as NUF2, CCNE2, NFIB, ETV5, KLF5, ATAD2, NDC80, and ZWINT. In
      addition, 39 individual DEGs demonstrated a minimum 2-fold copy number-associated
      expression change (median: 5.35, 95% CI: 4.53-16.98) and Pearson's correlation
      coefficient >= 0.6 (p < 0.05), of which PTP4A3 showed the highest correlation
      (CNV-FC = 21362.13; Pearson's correlation coefficient = 0.9983; p = 0.037). Two
      distinct groups of genes belonging to each SCEC and nonmalignant tissues were
      observed upon unsupervised two-way (genes and samples) hierarchical clustering.
      Conclusions. The current investigation is the first to produce data regarding the
      genomic signature of SCEC at the transcription level and in relation to CNVs. Our
      preliminary data indicate possible key roles of WNT and notch signaling in SCEC
      and overexpressed PTP4A3 as a potential therapeutic target. Further validation of
      our findings is warranted.

PMID- 30228820
TI  - Efficient Promotion of Autophagy and Angiogenesis Using Mesenchymal Stem Cell
      Therapy Enhanced by the Low-Energy Shock Waves in the Treatment of Erectile
      Dysfunction.
AB  - Background: Mesenchymal stem cell therapy (MSCT) and defocused low-energy shock
      wave therapy (ESWT) has been shown to ameliorate erectile dysfunction (ED).
      However, the interactions and effects of action between MSCT and ESWT remain
      poorly understood. In this study, we investigated the mechanisms of combination
      therapy with MSCT and ESWT in a rat model of diabetic ED. Materials and Methods:
      Eight-week-old male Sprague-Dawley rats were randomly divided into 2 parts.
      Diabetic rats induced by streptozotocin (65 mg/kg) were randomly divided into 4
      groups: (1) DM control group, (2) DM + ESWT group, (3) DM + MSCT group, and (4)
      DM + ESWT + MSCT group. The sham group was a normal control group (without
      streptozotocin). MSCT and (or) ESWT were, respectively, administered to each
      group according to the proposal for 8 weeks. Immediately after recording of
      intracavernous pressure (ICP), the penis was then harvested for histologic
      analysis, ELISA, and Western blotting. Results: The ratio of ICP/MAP was
      significantly higher in the DM + ESWT + MSCT group than in ESWT or MSCT treated
      group (P < 0.05). Also, the treatment stimulated angiogenesis and vasodilatation
      in the corpus cavernosum (P < 0.05). ESWT increased the quantity of MSCs in the
      corpus cavernosum and also induced MSCs to express more VEGF in vitro and vivo (P
      < 0.05) which activated the PI3K/AKT/mTOR and NO/cGMP signaling pathways in the
      corpus cavernosum. The combination approach stimulated autophagy and decreased
      apoptosis in the corpus cavernosum. NGF and BDNF expressions were higher in the
      DM + ESWT + MSCT group than in the DM control group (P < 0.01). Furthermore, the
      treatment promoted the MSC recruitment by inducing penile tissues to express more
      PECAM and SDF-1. Conclusions: Combination of LI-ESWT and MSCT can get a better
      result than a single treatment by expressing more VEGF which can take part in
      autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative
      therapy would provide a new research direction in ED treatment for the future.

PMID- 30228823
TI  - Knowledge, Attitude, and Practice on Hygiene and Morbidity Status among Tertiary
      Students: The Case of Kotebe Metropolitan University, Addis Ababa, Ethiopia.
AB  - Considerable fractions of the world's diseases are communicable, of which over
      60% are infectious. Knowledge, attitude, and practice of hygiene are very
      important to decrease these disease burdens especially in places like higher
      education institutions. This study is aimed at revealing the status and gaps on
      knowledge, attitude, and practice of hygiene among Kotebe Metropolitan University
      students. Alongside, morbidity records of the students' clinic are reviewed.
      Sampled regular students who are boarding and who serve the students' canteen are
      studied. The investigation applied a cross-sectional study design. A structured
      questionnaire is administered following a pretest, and the data collected are
      analyzed using "SPSS v.20." The review on morbidity record showed that the
      leading infections so far are respiratory (47%), gastrointestinal (amoebiasis,
      giardiasis, and typhoid) (34%), and eye and skin infections (16%). Regarding the
      responses to the knowledge questions, 1451 (60.8%) were correct while 934 (39.2%)
      were incorrect. Concerning handwashing as knowledge question, significant
      difference (p ~ 0.00) existed between genders. Over 50% of the respondents do
      think parasitic infections typically amoeba is acquired not due to the
      contaminated vegetables, but rather they assume that such vegetables trigger
      those parasites already lodging in their gut. Above 60% of the respondents agreed
      that sharing drinking cups as a sign of affection as unfavorable attitude. In
      relation to that, the students' attitude highly varies by gender. However, the
      responses on hygiene practice enquiries appear to be promising. Further, the
      students do some practice while not having the desired level of knowledge on
      hygiene. Generally, there is a considerable gap in the knowledge, attitude, and
      practice of hygiene among students.

PMID- 30228824
TI  - Community Pharmacists' Knowledge, Attitudes, and Practice of Herbal Medicines in
      Asir Region, Kingdom of Saudi Arabia.
AB  - Background: A dramatic increase in the use of natural products and herbal
      medicines has been observed globally. Simultaneously, there has been an increase
      in safety concerns regarding the extensive use of these herbal remedies among
      health care practitioners. The urban and rural populations of Saudi Arabia still
      rely on traditional Arabic herbal medicines for the treatment of various
      diseases. Objectives: This study aimed to evaluate community pharmacists'
      knowledge, attitudes, and practices of herbal medicines in the Asir region, Saudi
      Arabia. Methods: An online cross-sectional study was conducted among 233
      community pharmacists using a structured questionnaire. Results: Pharmacists
      showed considerable knowledge of the indications of herbal products, with an
      average score of 84% correct answers, total P value < 0.05 and < 0.001. They were
      also knowledgeable about contraindications, side effects, and interactions, with
      an average score of 75% correct answers, total P value < 0.05 and < 0.001.
      Community pharmacists had a positive attitude towards herbal products, as 71% of
      them "agreed" or "strongly agreed" that herbal products were efficacious and 77%
      of them "agreed" or "strongly agreed" that those products should be sold only in
      a pharmacy. Herbal products were "often" or "always" dispensed by 67.3% of
      pharmacists in a pharmacy. Conclusion: Pharmacists generally exhibited good
      knowledge, a positive attitude, and effective practice towards herbal products.
      However, continuing education programs are needed to train pharmacists in
      providing client counseling on herbal medicine usage and dispensing them.

PMID- 30228822
TI  - EZH1 Is Associated with TCP-Induced Bone Regeneration through Macrophage
      Polarization.
AB  - Macrophages have been found to regulate the effects of biomaterials throughout
      the entire tissue repair process as an antigen-presenting cell. As a well-defined
      osteoconductive biomaterial for bone defect regeneration, tricalcium phosphate
      (TCP) has been found to facilitate a favourable osteoimmunomodulatory response
      that can shift macrophage polarization towards the M2 phenotype. In the present
      study, our group discovered that a histone methyltransferase enhancer of zeste1
      (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating
      that EZH1 may participate in the macrophage phenotype shifting. Furthermore, the
      NF-kappaB pathway in macrophages was significantly downregulated through
      stimulation of TCP, suggesting a potential interaction between EZH1 and the NF
      kappaB pathway. Utilizing gene knock-down therapy in macrophages, it was found
      that depletion of EZH1 induced M2 macrophage polarization but did not
      downregulate NF-kappaB. When the NF-kappaB pathway was inhibited, the expression
      of EZH1 was significantly downregulated, suggesting that the inhibition of EZH1
      may be regulated by the NF-kappaB pathway. These novel findings provide valuable
      insights into a potential gene target system that controls M2 macrophage
      polarization which ultimately favours a microenvironment suitable for bone
      repair.

PMID- 30228825
TI  - Complementary and Alternative Therapies for Inflammatory Diseases 2018.

PMID- 30228826
TI  - Single Oral Acute Toxicity of Banhasasim-Tang and Its Antiobesity Effect on Diet
      Induced Obese Mice and 3T3-L1 Adipocytes.
AB  - We had tested antiobesity effect of 52 traditional herbal formulas in 3T3-L1
      adipocyte, and Banhasasim-tang (BHSST) was chosen as one of the effective
      medications to inhibit triglyceride accumulation. We investigated the antiobesity
      effect of BHSST on 3T3-L1 adipocytes and high-fat diet- (HFD-) induced obese
      mice. In addition, we evaluated the acute toxicity of BHSST in Sprague Dawley
      (SD) rats. Differentiated 3T3-L1 cells were treated with various concentrations
      of BHSST for 8 days. Accumulated triglyceride level and the expressions of
      adipogenesis-related genes and proteins were subsequently investigated. To
      evaluate the single oral toxicity of BHSST, the SD rats of each sex were
      administered a single dose (5000 mg/kg) of BHSST via oral gavage; the control
      group received vehicle only. After a single administration, the mortality,
      clinical signs, gross findings, and body weight were monitored for 15 days. Male
      C57BL/6J mice were fed HFD for 4 weeks to induce obesity and randomly received 50
      mg/kg of Orlistat (n=12, OR), 200 mg/kg of BHSST (n=12, B200), and 1000 mg/kg of
      BHSST (n=12, B1000) for another 8 weeks. BHSST suppressed the triglyceride
      contents and lipid accumulation in a dose-dependent manner in 3T3-L1 adipocytes.
      BHSST also downregulated the adipogenesis-related gene levels and protein
      expression compared with those in undifferentiated adipocytes. In a single oral
      dose toxicity study, there was no adverse effect on mortality, clinical signs,
      body weight changes, and gross findings in the treatment group. HFD-fed mice
      treated with BHSST showed significantly reduced body weight gain, food efficiency
      ratio, and white adipose tissue weight. The medial lethal dose (LD50) of BHSST
      was 5000 mg/kg/day body weight for each sex in the rats. BHSST decreased the body
      weight gain in HFD-fed obese mice and inhibited triglyceride accumulation via a
      cascade of multiple factors at the mRNA and protein levels in 3T3-L1 adipocytes.

PMID- 30228827
TI  - Association Rule Analysis for Validating Interrelationships of Combined
      Medication of Compound Kushen Injection in Treating Colon Carcinoma: A Hospital
      Information System-Based Real-World Study.
AB  - Background: Real world evidence is important for informing healthcare practice
      and developing medical products and has gained broad interest in healthcare.
      Compound Kushen Injection (CKI) has been widely applied into treatment of colon
      carcinoma (CC) in China. Postapproval drug assessment related retrospective
      studies using electrical medical record (EMR) collected from hospital information
      system (HIS) is one of the most important categories of real-world study (RWS).
      Based on HIS EMR, interrelationships of combined medication of CKI in treating CC
      can be validated in real world settings. Methods: This study was conducted based
      on a large-scale integrated database of EMR derived from HIS. EMR of 3328
      patients initially diagnosed with CC among 49,597 patients treated with CKI were
      included in the study. Descriptive statistical analyses and apriori algorithm
      based association rule analyses were performed, respectively, to validate
      frequency distribution and interrelationships of combined medication of CKI in
      treating CC. Results: The pharmacological mechanisms of TCMs that have been
      commonly used in conjunction with CKI include heat-clearing and detoxifying, qi
      reinforcing, blood circulation-promoting and stasis-removing, blood-stanching,
      and qi-regulating. For modern medicines, antibiotics, antineoplastic
      chemotherapeutic drugs, immunomodulator, 5-HT receptor antagonist drugs, and
      corticosteroids are most often combined with CKI. The association rules of
      medication combinations of CKI in treating CC in real world manifest certain laws
      for both TCMs and modern medicines. They are generally in line with CC treatment
      guidelines. Conclusions: It is a common practice for CKI to be integrated with
      both modern medicines and TCMs when treating CC in China. The associations of
      medication combinations of CKI in treating CC manifest certain laws for both TCMs
      and modern medicines. The RWS for validating interrelationships of combined
      medication may provide evidence for rational use of CKI. Further explorations are
      needed to verify and expand the conclusions.

PMID- 30228828
TI  - Antioxidant Activity and In Vitro Antiglycation of the Fruit of Spondias
      purpurea.
AB  - Hyperglycemia in diabetes mellitus causes irreversible life-threatening micro-
      and macrovascular complications. There is evidence that the glycation reaction
      leads to a chemical modification of the proteins contributing to the
      complications of diabetes. It is known that advanced glycation end products
      (AGEs) are formed by glycation and oxidation reactions called glycoxidation. CML,
      a nonfluorescent AGE, has become a biomarker of glycoxidative damage; other AGEs
      appear to induce oxidative stress, which results in cytotoxicity. To determine
      antioxidant activity, the FRAP, DPPH, and TEAC tests were used, as well as the
      polyphenols content using Folin-Ciocalteu's method. To evaluate the antiglycation
      activity, the BSA/glucose system was used, and the fructosamine concentration,
      protein carbonyl content, thiol, and CML groups were determined. The results
      obtained show that the hexane extract of the fruit of Spondias purpurea (CFH)
      effectively inhibits the glycation reaction, in addition to increasing the thiol
      groups and decreasing levels of fructosamine, protein carbonyl, and CML. In
      addition, CFH presented significant antioxidant activity. CFH inhibits the
      glycation reaction; therefore, it can help prevent complications related to AGEs
      in diabetes mellitus; it also reduces oxidative stress and is effective in
      protecting proteins from oxidative damage.

PMID- 30228830
TI  - SIR Model for Dengue Disease with Effect of Dengue Vaccination.
AB  - The dengue disease is caused by dengue virus, and there is no specific treatment.
      The medical care by experienced physicians and nurses will save life and will
      lower the mortality rate. A dengue vaccine to control the disease is available in
      Thailand since late 2016. A mathematical model would be an important way to
      analyze the effects of the vaccination on the transmission of the disease. We
      have formulated an SIR (susceptible-infected-recovered) model of the transmission
      of the disease which includes the effect of vaccination and used standard
      dynamical modelling methods to analyze the effects. The equilibrium states and
      their stabilities are investigated. The trajectories of the numerical solutions
      plotted into the 2D planes and 3D spaces are presented. The main contribution is
      determining the role of dengue vaccination in the model. From the analysis, we
      find that there is a significant reduction in the total hospitalization time
      needed to treat the illness.

PMID- 30228829
TI  - Inhibition of alpha-Glucosidase, Intestinal Glucose Absorption, and Antidiabetic
      Properties by Caralluma europaea.
AB  - Many medicinal plants around the world are used for therapeutic purposes against
      several diseases, including diabetes mellitus. Due to their composition of
      natural substances that are effective and do not represent side effects for
      users, unlike synthetic drugs, in this study, we investigated the inhibitory
      effect of Caralluma europaea (CE) on alpha-glucosidase activity in vitro; then
      the kinetics of the enzyme were studied with increasing concentrations of sucrose
      in order to determine the inhibition type of the enzyme. In addition, this effect
      of Caralluma europaea (CE) was confirmed in vivo using rats as an experimental
      animal model. Among the five fractions of CE, only the ethyl acetate fraction of
      C. europaea (EACe) induced a significant inhibition of alpha-glucosidase and its
      inhibition mode was competitive. The in vivo studies were conducted on mice and
      rats using glucose and sucrose as a substrate, respectively, to determine the
      oral glucose tolerance test (OGTT). The results obtained showed that the EACe and
      the aqueous extract of C. europaea (AECe) have significantly reduced the
      postprandial hyperglycemia after sucrose and glucose loading in normal and
      diabetic rats. AECe, also, significantly decreased intestinal glucose absorption,
      in situ. The results obtained showed that Caralluma europaea has a significant
      antihyperglycemic activity, which could be due to the inhibition of alpha
      glucosidase activity and enteric absorption of glucose.

PMID- 30228831
TI  - Fatigue and its associated factors in microscopic colitis.
AB  - Background: Fatigue is a well-recognized symptom in patients with inflammatory
      bowel disease and irritable bowel syndrome (IBS), and has been associated with
      psychological comorbidity and impaired quality of life in both. However, features
      associated with fatigue in patients with microscopic colitis (MC) are less clear.
      Materials and methods: We conducted a cross-sectional survey of patients with a
      new diagnosis of MC including levels of anxiety, depression, somatization,
      quality of life, and IBS-type symptoms. Levels and impact of fatigue were
      assessed using the Inflammatory Bowel Disease Fatigue self-assessment scale. Mean
      scores were compared against various patient characteristics, and were also
      correlated with anxiety, depression, somatization, and quality-of-life scores.
      Results: In total, 129 patients with MC diagnosed between 2010 and 2015 returned
      completed postal questionnaires. Common histological subtypes were collagenous
      colitis (53.5%, n = 69) and lymphocytic colitis (38.8%, n = 50). Higher mean
      fatigue severity and impact scores were associated with the presence of irritable
      bowel-syndrome-type symptoms, abnormal levels of anxiety and depression, and high
      levels of somatization (p < 0.0001 for all), but those reporting ongoing symptoms
      attributable to MC did not report significantly higher scores. There were
      significant positive correlations between total anxiety, depression, or
      somatization scores and fatigue severity and impact scores, and significant
      negative correlations with quality-of-life measures (p < 0.001 for all).
      Conclusions: Fatigue in MC appears to be associated with reporting IBS-type
      symptoms, psychological comorbidity and impaired quality of life. It may
      therefore represent an important target for treatment.

PMID- 30228834
TI  - Hyperacute intracranial aneurysm rebleed captured on planar and 3D digital
      subtraction angiography.

PMID- 30228833
TI  - Surveillance of Antibiotic Prescribing in Intensive Care Units in Poland.
AB  - Antibiotic use and microbial resistance in health care-associated infections are
      increasing globally and causing health care problems. Intensive Care Units (ICUs)
      represent the heaviest antibiotic burden within hospitals, and sepsis is the
      second noncardiac cause of mortality in ICUs. Optimizing appropriate antibiotic
      treatment in the management of the critically ill in ICUs became a major
      challenge for intensivists. We performed a surveillance study on the antibiotic
      consumption in 108 Polish ICUs. We determined which classes of antibiotics were
      most commonly consumed and whether they affected the length of ICU stay and the
      size and category of the hospital. A total of 292.389 defined daily doses (DDD)
      and 192.167 patient-days (pd) were identified. Antibiotic consumption ranged from
      620 to 3960 DDD/1000 pd. The main antibiotic classes accounted for 59.6% of the
      total antibiotic consumption and included carbapenems (17.8%), quinolones (14%),
      cephalosporins (13.7%), penicillins (11.9%), and macrolides (2.2%), respectively,
      whereas the other antibiotic classes accounted for the remainder (40.4%) and
      included antifungals (34%), imidazoles (20%), aminoglycosides (18%),
      glycopeptides (15%), and polymyxins (6%). The most consumed antibiotic classes in
      Polish ICUs were carbapenems, quinolones, and cephalosporins, respectively. There
      was no correlation between antibiotic consumption in DDD/1000 patient-days, mean
      length of ICU stay, size of the hospital, size of the ICU, or the total amount of
      patient-days. It is crucial that surveillance systems are in place to guide
      empiric antibiotic treatment and to estimate the burden of resistance.
      Appropriate use of antibiotics in the ICU should be an important public health
      care issue.

PMID- 30228835
TI  - Giant cell tumor of a rib following denosumab treatment.
AB  - Giant cell tumor (GCT) of the bone is an aggressive lytic lesion, commonly
      treated with surgery. Denosumab is a relatively recently introduced osteoclast
      activation inhibitor used for neoadjuvant therapy of GCT. Here we report the case
      of a GCT of a rib undergoing extensive osteosclerosis on computed tomography
      imaging following treatment with denosumab.

PMID- 30228832
TI  - Predictors of Sleep Apnea in the Canadian Population.
AB  - Older age, obesity, hypertension, snoring, and excessive daytime sleepiness have
      been associated with sleep apnea. The objective of this study was to determine
      the prevalence (crude and adjusted), as well as the risk factors, of sleep apnea
      in the adult Canadian population. Data from the 2009 Sleep Apnea Rapid Response
      (SARR) questionnaire were used to identify the risk factors, and all sleep
      related questions in the SARR questionnaire were used. The outcome variable of
      interest was health professional-diagnosed sleep apnea. Covariates of interest
      were demographic variables, population characteristics, respiratory and
      cardiovascular diseases, and enabling resources. The multiple logistic regression
      model adjusted for the clustering effect was used to analyze the data. Sleep
      apnea was diagnosed in 858,913 adults (3.4% of the population), and more men
      (65.4%) than women (34.6%) were diagnosed with sleep apnea. Multivariable
      logistic regression analysis indicated that age (45 and older), loud snoring,
      sudden awakening with gasping/choking (rare/sometimes and once or more a week),
      and nodding off/falling asleep in driving in the past 12 months were
      significantly associated with diagnosed sleep apnea. Predictive probability
      demonstrated that in overweight and obese persons, >=15 minutes of daily exercise
      significantly decreased the risk of diagnosed sleep apnea. The conclusion of this
      study is that in the Canadian population, sleep apnea is associated with older
      age, loud snoring, and sleeping problems. The protective effect of exercise
      warrants further investigation.

PMID- 30228836
TI  - Bladder diverticuli following injection of onabotulinum toxin A in a patient with
      multiple sclerosis and autosomal dominant polycystic kidney disease.
AB  - Urinary incontinence due to neurogenic detrusor overactivity is common in
      patients with disorders of lower motor neurons controlling the bladder. Multiple
      sclerosis is a major cause of neurogenic detrusor overactivity, which negatively
      impacts quality of life. Bladder wall injection of onabotulinum toxin A can
      diminish spontaneous bladder contraction, urinary urgency, and urge incontinence.
      Herein we report a 61-year-old woman with multiple sclerosis and autosomal
      dominant polycystic kidney disease with bladder trabeculation developing after
      repeated injections of onabotulinum toxin A.

PMID- 30228837
TI  - Preoperative diagnosis of the sclerosed hemangioma of the liver using
      multimodality imaging findings: A case report.
AB  - A sclerosed hemangioma of the liver is a rare benign lesion characterized by
      fibrosis and hyalinization of a hepatic cavernous hemangioma as a result of
      degeneration. This condition has been difficult to correctly diagnose with
      imaging. Our patient was a 57-year-old man whose computed tomography (CT) scan
      showed a mass of 45 mm in diameter in the lateral segment. On dynamic contrast
      enhanced CT, the lesion was found to comprise peripheral, gradual, and
      heterogeneous enhanced areas with a central nonenhanced area; malignancy was
      suspected. On magnetic resonance imaging, the peripheral area showed slight
      hperintensity on T2-weighted image, and showed a similar intensity on T1- and
      diffusion-weighted images as compared to the background liver and gradual
      enhancement, and the presence of abundant fibrous tissue was suspected.
      Conversely, the central area showed remarkable hyperintensity on T2-weighted
      images and no enhancement, and degeneration or hyalinization was suspected. The
      mass showed no uptake of fluorine-18 fludeoxyglucose (FDG). Some imaging findings
      suspected a benign tumor, and sclerosed hemangioma with abundant fibrosis and
      hyalinization was pathologically confirmed. Herein, we report a case of sclerosed
      hemangioma focusing on possible preoperative diagnosis using a combination of
      multimodality imaging findings-diffusion-weighted imaging and FDG-positron
      emission tomography imaging.

PMID- 30228839
TI  - Successful endovascular treatment of ruptured bilateral ophthalmic frontal dural
      arteriovenous fistula.
AB  - Bilateral ophthalmic-ethmoidal dural arteriovenous fistulas (DAVFs) are extremely
      rare and may present as complex lesions. These DAVFs are associated with high
      risk of intracranial hemorrhage but can be presented with ocular symptoms,
      cranial nerve palsy or epistaxis. Endovascular approaches have been used to
      manage an increasing proportion of complex intracranial DAVFs safely and with
      good clinical results. We present a patient with subdural hematoma and severe
      epistaxis due to ruptured bilateral ophthalmic-ethmoidal DAVF that was
      successfully treated by transarterial embolization with precipitating hydrophobic
      injectable liquid.

PMID- 30228838
TI  - Advanced neuroimaging in Balo's concentric sclerosis: MRI, MRS, DTI, and ASL
      perfusion imaging over 1 year.
AB  - Balo concentric sclerosis (BCS) is a rare, atypical demyelinating disease, which
      may rapidly progress to become severe and fatal. Advanced neuroimaging has proven
      helpful for early diagnosis, classification, prognostication, and monitoring of
      progression in multiple sclerosis, but has not been fully explored in BCS. We
      present the case of a 27-year-old woman with BCS in whom advanced neuroimaging
      was used to correlate the evolution of disease with clinical findings over the
      course of 1 year. Magnetic resonance imaging, magnetic resonance spectroscopy
      (MRS), diffusion tensor imaging (DTI), and arterial spin labeling cerebral
      perfusion were obtained at presentation (Day 0), and at Day 67 and Day 252.
      Imaging features include multilayered concentric ring lesion, reduced diffusion
      along the rim, hypoperfusion with possible mild central hyperperfusion, and MRS
      findings of increased choline, decreased N-acetylaspartate (NAA), and possible
      presence of lactate and/or lipid peak. DTI tractography and relative apparent
      diffusion coefficient analyses correlated with clinical symptoms and may help to
      determine extent of white matter tract injury and prognosis.

PMID- 30228840
TI  - Low-grade intramedullary osteosarcoma presenting with multiple sclerotic bone
      lesions.
AB  - Low-grade intramedullary osteosarcoma is a less-aggressive type of osteosarcoma
      for which delays in diagnosis are common. We present the case of a 42-year-old
      woman with complaints of low back pain. Multiple imaging evaluations and biopsy
      procedures were necessary to make the final diagnosis. The key radiologic feature
      was multiple sclerotic lesions throughout the skeleton, best seen on the bone
      scan. The difficulties in diagnosing this condition are evident in this case.

PMID- 30228841
TI  - Coexisting cystic lung disease as a rare extra-renal manifestation of autosomal
      dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) classically presents with
      multiple bilateral renal cysts and ultimately progresses to end stage renal
      disease. While many of the extra-renal manifestations of ADPKD are well
      documented, associated pulmonary findings are particularly rare, having only been
      recently been reported in a handful of studies to date. A 69-year-old female with
      ADPKD presented to our hospital with respiratory complaints. High resolution
      computed tomography revealed bronchiectasis, cystic lung disease, and
      interstitial fibrosis. The patient did not have concurrent risk factors or
      coexisting disease processes to explain the etiology of her airway and cystic
      lung disease, which we suggest are manifestations of ADPKD. We have not found a
      previous report of interstitial lung disease in this setting.

PMID- 30228842
TI  - Isolated traumatic pectoralis minor tendon tear in a young adult diagnosed with
      MRI.
AB  - This is a rare case of an isolated pectoralis minor partial-thickness tendon tear
      in a 24-year-old man who was involved in a major trauma. The purpose of this
      paper is to report the clinical signs, symptoms, cross-sectional imaging
      findings, and management of an isolated pectoralis minor tendon tear.
      Furthermore, this case represents a novel traumatic mechanism of injury, as
      opposed to the classic sports-related pectoralis minor tendon tear injury. The
      current limited body of literature on isolated pectoralis minor tendon tears is
      reviewed.

PMID- 30228843
TI  - A unique case of benign intracranial hemangioma mimicking malignant
      transformation.
AB  - Capillary hemangiomas are rare benign vascular lesions, commonly found on scalp,
      face, chest, or back of a neonate or infant. Hemangiomas of the central nervous
      system are very rare lesions. There are only a few cases of intracranial
      capillary hemangioma (ICH) arising in adults reported in the literature. We
      present a case of 59-year-old female with intermittent recurrent headache
      localized in the frontal area. Magnetic resonance imaging revealed left frontal
      extra-axial mass with peripheral enhancement. The patient underwent complete
      surgical resection of the tumor. Histopathology examination of the lesion
      revealed well defined vascular lesion composed of closely packed plump
      endothelial cells lining slit-like vascular channels containing scattered red
      blood cells. No evidence of infiltrative brain parenchyma was seen. Ki-67
      proliferative index was low, less than 2%. The final diagnosis was confirmed to
      be ICH by histopathology and immunohistochemistry studies. The patient has
      remained healthy and free of disease 39 months since her initial surgery. ICH is
      a benign vascular lesion which rarely occurs in the central nervous system,
      particularly in the intracranial region. It can mimic malignant lesions on
      radiologic studies. Histopathology examination is the gold standard for
      diagnosis. If total resection is achieved, prognosis is generally good with no
      evidence of recurrence.

PMID- 30228844
TI  - Pyogenic brain abscess, ventriculitis and diffuse meningitis with fatal outcome
      in an adult: Radiologic-pathologic correlation?,.
AB  - Rupture of brain abscesses with evolution into ventriculitis with meningitis may
      result in sudden and dramatic worsening of the clinical situation. We present a
      57-year-old man with such an event and fatal outcome. Multiple imaging modalities
      including computed tomography and advanced magnetic resonance imaging were
      correlated with gross specimen and histologic images. The differential diagnosis
      of multiple lesions with ring enhancement and prominent perifocal edema includes
      mainly infectious and neoplastic processes, such as brain abscess, metastasis,
      and multicentric glioblastoma. Pyogenic ventriculitis is an uncommon
      manifestation of severe intracranial infection that might be clinically obscure.
      We discuss the characteristic magnetic resonance findings of brain abscess and
      its complications, including meningitis and ventriculitis with emphasis on the
      role of diffusion-weighted and fluid-attenuated inversion recovery imaging.

PMID- 30228845
TI  - Spinal canal meningioma mimicking posterior fossa ischemia on CT perfusion: A CT
      perfusion pitfall.
AB  - The recent approach to treat acute stroke is to extend treatment window in
      patients with salvageable peri-infarct ischemia which increases the application
      of the perfusion imaging, specifically computed tomography perfusion (CTP). In
      this paper, I am presenting a case of left middle cerebral artery infarction
      which was evaluated by CTP under "code stroke." The patient had an incidental
      spinal canal meningioma which was out of field of view in CTP but mimicked right
      cerebellar ischemia on CTP. Although ischemia has been previously reported within
      the peripheral parenchymal edema surrounding a meningioma, in this patient there
      was no evidence of edema in the right cerebellum on magnetic resonance imaging. I
      believe the CTP findings are secondary to steal phenomena at right vertebral
      artery or compression upon the venous plexus. Recently, by using modern computed
      tomography scanners, it is common to cover the entire brain in CTP. The emergency
      radiologist should be aware of this pitfall that spinal canal pathologies which
      are out of field of view can mimic posterior fossa ischemia.

PMID- 30228846
TI  - Bilateral persistent primitive hypoglossal artery presenting with hemiplegia?.
AB  - The manuscript describes an unusual vascular anomaly. Persistence of carotid
      vertebrobasilar anastomosis is a rare occurrence with presence of bilateral
      hypoglossal arteries (HAs) rarer still. We present a case of bilateral persistent
      HAs with hypoplastic vertebral arteries which end into posterior inferior
      cerebellar arteries. The computed tomography and magnetic resonance imaging
      appearance, course, and other associations are discussed. A review of 6 cases of
      bilateral HA published in the world literature is also discussed.

PMID- 30228847
TI  - Obtuse marginal coronary artery aneurysm on CT coronary angiogram.
AB  - Coronary artery aneurysms are rare. We present an unusual case of an isolated
      coronary artery aneurysm in the obtuse marginal artery detected on a computed
      tomographic coronary angiogram, which is unlikely to be significant for the
      patient. A Medline literature search did not find a similar case.

PMID- 30228848
TI  - Pancreatic desmoid tumor: A rare case with radiologic-pathologic correlation.
AB  - A 39-year-old female patient was referred to our tertiary oncologic center for
      additional investigations relating to a suspect pancreatic tail lesion. An
      abdominal computed tomography scan and magnetic resonance imaging scan showed a
      solid lesion demonstrating progressive enhancement. Complete resection was
      obtained and the final diagnosis was that of a desmoid tumor of the pancreas, an
      exceptionally rare tumor demonstrating overlap with other solid and cystic
      lesions of the pancreas [1]. Therefore, it is important to recognize the
      essential role of pathology, particularly immunohistochemistry, in identifying
      this tumor. The high rate of postsurgical recurrence should prompt repeated
      follow-ups considering the potential aggressive nature of desmoid tumors.

PMID- 30228849
TI  - Boerhaave syndrome in an elderly man successfully treated with 3-month indwelling
      esophageal stent.
AB  - Boerhaave syndrome refers to a spontaneous perforation of the esophagus that
      results from severe straining or vomiting. This uncommon situation may lead to
      serious outcome with chemical mediastinitis, and is associated with high
      morbidity and mortality. Surgery, although associated with high morbidity and
      mortality remains the treatment of choice, whereas endoscopic management with
      stent placement is preserved to treat inoperable patients. Removal of the stent
      is generally recommended after 4-6 weeks. We report a case of an elderly patient
      who presented with a large complicated Boerhaave's mid-esophageal perforation,
      with a complete recovery after a 3-month treatment with a long esophageal stent.

PMID- 30228850
TI  - Left neck undifferentiated sarcoma with synchronous left kidney renal cell
      carcinoma.
AB  - Parapharyngeal space sarcomas are rare malignancies and most in the reported
      literature are synovial sarcomas. Here we present the case of a 27-year-old
      female with a painless, left-sided neck mass who underwent computed tomography
      and magnetic resonance imaging evaluation which demonstrated a benign appearing
      mass that upon resection unexpectedly proved to be a high-grade undifferentiated
      sarcoma with rhabdoid features. Staging computed tomography revealed a
      synchronous renal cell carcinoma with clear cell and papillary features. Despite
      an extensive genetic work-up no underlying cause linking these two cancers was
      discovered.

PMID- 30228851
TI  - Immediate reaction to gadolinium based contrast agent with fatal outcome.

PMID- 30228852
TI  - Design and Simulation Study of a CNT-Based Multisource Cubical CT System for
      Dynamic Objects.
AB  - The purpose of this paper is to design and simulate a new computed tomography
      (CT) system with a high temporal resolution for dynamic objects. We propose a
      multisource cubical CT (MCCT) system with X-ray tubes and detectors installed on
      a cube. Carbon nanotube- (CNT-) based X-ray focal spots are distributed on the
      twelve edges of the cube. The distribution of X-ray focal spots and detectors
      completely avoids mechanical movements to scan an object under inspection. CNTs
      are excellent electron field emitters because the use of a "cold" cathode makes
      it possible to fabricate a cathode with multiple electron emission points, and
      the CNT-based X-ray focal spots possess little response time and programmable
      emission. The proposed rotation-free MCCT system can acquire a high scanning
      speed when using a high frame rate detector. A three-dimensional (3D)
      reconstruction algorithm with tensor framelet-based L0-norm (TF-L0) minimization
      is developed for the simulation study of the MCCT. Simulation experiment results
      demonstrate the feasibility of the MCCT system.

PMID- 30228853
TI  - Influence of Diosmin Treatment on the Level of Oxidative Stress Markers in
      Patients with Chronic Venous Insufficiency.
AB  - Oxidative stress plays an important role in the pathophysiology of many human
      disorders, while antioxidants prevent the development of various adverse
      symptoms. Diosmin is a natural flavonoid applied in vascular system disorders,
      especially in chronic venous insufficiency (CVI), and it plays a significant part
      in the alleviation of CVI symptoms. Due to antioxidant activity, it also has the
      ability to scavenge the oxygen free radicals and hence decreases the level of
      oxidative stress biomarkers, such as prostaglandins and their precursors
      isoprostanes. In the study, the influence of diosmin treatment on the level of
      isoprostanes in plasma samples of patients suffering from CVI was examined. The
      qualitative analysis was performed using high-performance liquid chromatography
      with spectrometry detection (LC-MS). The statistically significant decrease of
      isoprostane content after 3 months of treatment was observed within the studied
      group; however, the most significant changes were observed in patients who smoke.

PMID- 30228854
TI  - Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT
      to Cause Oxidative Damage in the Striatum of Mice.
AB  - Excessive manganese (Mn) can accumulate in the striatum of the brain following
      overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced
      neurotoxicity. It has been proven that glutathione (GSH) depletion is a key
      factor in oxidative damage during Mn exposure. However, no study has focused on
      the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn
      exposure. The objective of the present study was to explore the mechanism of Mn
      disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary
      neurons and astrocytes were cultured and treated with different doses of Mn to
      observe the state of cells and levels of GSH and reactive oxygen species (ROS)
      and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly
      divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2,
      500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) +
      50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for
      two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein
      sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and
      ultrastructural features in the striatum of mice were measured. Mn reduced
      protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and
      xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8
      OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and
      ultrastructure changes in the striatum of mice were significantly present. In
      conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of
      EAAC1 and xCT to trigger oxidative damage in the striatum.

PMID- 30228855
TI  - Neuroprotective Effects of Polydeoxyribonucleotide in a Murine Model of Cadmium
      Toxicity.
AB  - Cadmium (Cd) is a harmful heavy metal, which causes severe brain damage and
      neurotoxic effects. Polydeoxyribonucleotide (PDRN) stimulates adenosine A2A
      receptor, thus contrasting several deleterious mechanisms in course of tissue
      damages. We aimed to investigate the possible neuroprotective effect of PDRN in a
      murine model of Cd-induced brain toxicity. Male C57 BL/6J mice were treated as
      follows: vehicle (0.9% NaCl, 1 ml/kg/day), PDRN (8 mg/kg/day), CdCl2 (2
      mg/kg/day), and CdCl2 + PDRN. Animals were tested with the Morris water maze test
      to assess spatial memory and learning. After 14 days of treatment, brains were
      processed to evaluate the presence of edema in the cerebral tissue, the
      expression of mammalian target of rapamycin kinase (mTOR) and brain-derived
      neurotrophic factor (BDNF), and the morphological behavior of the hippocampal
      structures. After CdCl2 administration, the escape latency was high, protein
      expression of BDNF was significantly decreased if compared to controls, mTOR
      levels were higher than normal controls, and brain edema and neuronal damages
      were evident. The coadministration of CdCl2 and PDRN significantly diminished the
      escape latency, increased BDNF levels, and decreased protein expression of mTOR.
      Furthermore, brain edema was reduced and the structural organization and the
      number of neurons, particularly in the CA1 and CA3 hippocampal areas, were
      improved. In conclusion, a functional, biochemical, and morphological protective
      effect of PDRN against Cd induced toxicity was demonstrated in mouse brain.

PMID- 30228857
TI  - Treatment Outcomes and Associated Factors among Hospitalized Stroke Patients at
      Shashemene Referral Hospital, Ethiopia.
AB  - Background: The 2013 Global Burden of Disease report indicated that 80% of stroke
      deaths occur in low- and middle-income regions. Although stroke has been
      consistently reported as one of the three leading causes of morbidity and
      mortality in the past years in Ethiopia, there is a paucity of data regarding
      treatment outcomes of stroke if sufficient. Hence, the present study aimed to
      assess patterns of treatment outcomes and associated factors among hospitalized
      stroke patients at Shashemene Referral Hospital. Methods: A retrospective cross
      sectional study was conducted at the medical ward of Shashemene Referral
      Hospital. A total of 73 hospitalized stroke patients during the period 2012-2017
      were included in the study. Demographic characteristics, risk factors, and stroke
      types and their hospital outcomes were reviewed from the medical records of the
      patients. The data were entered and analyzed using SPSS version 16.0. Descriptive
      statistics such as percent and frequency were used to summarize patients'
      characteristics. Binary logistic regression was used to investigate the potential
      predictors of treatment outcome. A p-value <=0.05 was considered statistically
      significant. Result: Ischemic stroke was the most common type of stroke (65.8%)
      diagnosed in our setting. Hypertension (52.05%) was the common comorbid
      condition. More than half (54.79%) of the stroke patients improved on treatment.
      Dyslipidemics were prescribed to 68.49% of patients and the most popular
      antiplatelet was aspirin, which was prescribed to 61.64% of the study
      participants. Age, sex, type of stroke, and type of comorbidity were not
      significant factors of stroke treatment outcome. Conclusion: Ischemic stroke was
      the most common type of stroke diagnosed among the study participants while
      aspirin and statins were the most frequently used drugs in the management of
      stroke. Approximately 50% of hospitalized stroke patients had good treatment
      outcome and none of the investigated variables were significantly associated with
      the treatment outcomes.

PMID- 30228856
TI  - Tribulus terrestris Protects against Male Reproductive Damage Induced by
      Cyclophosphamide in Mice.
AB  - Tribulus terrestris (TT) has been considered as a potential stimulator of
      testosterone production, which has been related with steroidal saponins
      prevailing in this plant. Cyclophosphamide (CP) is the most commonly used
      anticancer and immunosuppressant drug, which causes several toxic effects,
      especially on the reproductive system. Patients who need to use CP therapy
      exhibit reduced fertility or infertility, which impacts both physically and
      emotionally on the decision to use this drug, especially among young men. We
      hypothesized that the treatment with TT dry extract would protect the male
      reproductive system against CP toxicity. Mice received dry extract of TT (11
      mg/kg) or vehicle by gavage for 14 days. Saline or CP was injected
      intraperitoneally at a single dose (100 mg/kg) on the 14th day. Animals were
      euthanized 24 h after CP administration, and testes and epididymis were removed
      for biochemical and histopathological analysis and sperm evaluation. The dry
      extract of TT was evaluated by HPLC analysis and demonstrated the presence of
      protodioscin (1.48%, w/w). CP exposure increased lipid peroxidation, reactive
      species, and protein carbonylation and altered antioxidant enzymes (SOD, CAT,
      GPx, GST, and GR). Moreover, acute exposure to CP caused a reduction on 17 beta
      HSD activity, which may be related to the reduction in serum testosterone levels,
      histopathological changes observed in the testes, and the quality of the semen.
      The present study highlighted the role of TT dry extract to ameliorate the
      alterations induced by CP administration in mice testes, probably due to the
      presence of protodioscin.

PMID- 30228858
TI  - Association of adverse childhood experiences with functional identity and
      impulsivity among adults: a cross-sectional study.
AB  - Introduction: The present study explores the association of adverse childhood
      experiences with impulsivity and functional identity among Pakistani adults.
      Methods: In this cross-sectional study, 260 Pakistani medical students aged 18
      and above were approached. A consent form, a questionnaire on sociodemographic
      characteristics, and an English versions of the Adverse Childhood Experiences
      (ACE) scale, Functions of Identity scale (FIS) and Barratt's Impulsiveness Scale
      (BIS-11) was employed in this study. All data were analyzed in SPSS v. 20.
      Results: A total of 122 (52.6%) of respondents had experienced at least one
      adverse childhood experience. According to linear regression analysis, ACE scores
      were significantly associated with increasing age, increasing order in birth,
      lower scores on functional identity structure and non-planning impulsivity, and
      higher scores on future (functional identity) and motor impulsivity. Conclusions:
      A high proportion of Pakistani medical students reported adverse childhood
      experiences, which lead to impulsive behaviors and poor functional identities.

PMID- 30228859
TI  - Software for web-based tic suppression training.
AB  - Exposure and response prevention (ERP) is a first-line behavior therapy for
      obsessive-compulsive disorder, and has also been tested in Tourette syndrome
      (TS). However, ERP for tic disorders requires intentional tic suppression, which
      for some patients is difficult even for brief periods. Additionally, practical
      access to behavior therapy is difficult for many patients, especially those in
      rural areas. The authors present a simple, working web platform (TicTrainer) that
      implements a strategy called reward-enhanced exposure and response prevention (RE
      ERP). This strategy sacrifices most expert therapist components of ERP, focusing
      only on increasing the duration of time for which the user can suppress tics
      through automated differential reinforcement of tic-free periods (DRO). RE-ERP
      requires an external tic monitor, such as a parent, during training sessions. The
      user sees increasing digital rewards for longer and longer periods of successful
      tic suppression, similar to a video game score. TicTrainer is designed with
      security in mind, storing no personally identifiable health information, and has
      features to facilitate research, including optional masked comparison of tics
      during DRO vs. noncontingent reward conditions. A working instance of TicTrainer
      is available from https://tictrainer.com/.

PMID- 30228861
TI  - Recent advances in the understanding and management of oropharyngeal cancer.
AB  - Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing health problem in
      the developing and developed world. In recent years, there have been major
      changes in the treatment paradigms for OPSCC. This is because of a number of
      reasons: the understanding and discovery of a new viral etiology (the human
      papillomavirus [HPV]), changes in practice patterns owing to advances in
      radiotherapy, and then an organ preservation strategy with the increased use of
      chemotherapy. Next came the development of new surgical technologies and the
      emergence of a new treatment modality, immunotherapy. In this article, we discuss
      the evolution of OPSCC treatments, starting with the traditional tobacco era.
      Treatment paradigms then evolved during the organ preservation era, the HPV era,
      and the minimally invasive surgery era. We are currently in the immunotherapy
      era, with a number of new drugs becoming available both on trial and by approval
      for use in the clinical setting for head and neck cancer patients. We discuss a
      number of trials and the reasons behind attempts at both treatment escalation and
      treatment de-escalation.

PMID- 30228860
TI  - An update on the pathogenesis and diagnosis of Diamond-Blackfan anemia.
AB  - Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia
      characterized by a block in erythropoiesis at the progenitor stage, although the
      exact stage at which this occurs remains to be fully defined. DBA presents
      primarily during infancy with macrocytic anemia and reticulocytopenia with 50% of
      cases associated with a variety of congenital malformations. DBA is most
      frequently due to a sporadic mutation (55%) in genes encoding several different
      ribosomal proteins, although there are many cases where there is a family history
      of the disease with varying phenotypes. The erythroid tropism of the disease is
      still a matter of debate for a disease related to a defect in global ribosome
      biogenesis. Assessment of biological features in conjunction with genetic testing
      has increased the accuracy of the diagnosis of DBA. However, in certain cases, it
      continues to be difficult to firmly establish a diagnosis. This review will focus
      on the diagnosis of DBA along with a description of new advances in our
      understanding of the pathophysiology and treatment recommendations for DBA.

PMID- 30228862
TI  - Recent advances in understanding DNA replication: cell type-specific adaptation
      of the DNA replication program.
AB  - DNA replication is an essential process occurring prior to cell division. Cell
      division coupled to proliferation ensures the growth and renewal of a large
      variety of specialized cell types generated during embryonic development. Changes
      in the DNA replication program occur during development. Embryonic
      undifferentiated cells show a high replication rate and fast proliferation,
      whereas more differentiated cells are characterized by reduced DNA synthesis and
      a low proliferation rate. Hence, the DNA replication program must adapt to the
      specific features of cells committed to different fates. Recent findings on DNA
      synthesis regulation in different cell types open new perspectives for developing
      efficient and more adapted therapies to treat various diseases such as genetic
      diseases and cancer. This review will put the emphasis on recent progress made in
      this field.

PMID- 30228863
TI  - Treatment of extended-spectrum beta-lactamase-producing Enterobacteriaceae
      (ESBLs) infections: what have we learned until now?
AB  - The spread of extended-spectrum beta-lactamase (ESBL)-producing
      Enterobacteriaceae (ESBL-PE) has dramatically increased worldwide, and this
      "evolving crisis" is currently regarded as one of the most important public
      health threats. The growing problem of ESBL-PE antimicrobial resistance seems to
      have a dual face between "Scylla and Charybdis": on one hand the potential for
      rapid spread and dissemination of resistance mechanisms and on the other hand the
      injudicious overuse of antimicrobial agents and the inadequate infection control
      measures, especially in the health-care setting. Given the World Health
      Organization's warning against a "post antibiotic era", health-care providers are
      at a critical standpoint to find a "balance" between safe and effective ESBL-PE
      treatment and avoidance of inducing further resistance mechanisms. The aim of the
      review is to summarize the updated published knowledge in an attempt to answer
      basic everyday clinical questions on how to proceed to effective and the best
      ESBL-PE treatment options based on the existing published data.

PMID- 30228866
TI  - Recent advances in understanding grasslands.
AB  - Grasslands are a vitally important ecosystem, supporting a wide range of
      ecosystem services and high levels of biodiversity. As a consequence, they have
      long been a focus for ecologists, playing host to some of the world's longest
      running ecological experiments and providing the inspiration for many long
      standing theories and debates. Because the field of grassland ecology is broad,
      encompassing many areas of ecology, this article picks some areas of particular
      debate and development to look at recent advances. The areas include
      relationships between diversity and productivity, ecosystem stability and
      ecosystem service provision, global change threats from nutrient addition,
      invasive species, climate change, and plant soil interactions.

PMID- 30228865
TI  - Recent advances in the understanding and treatment of pemphigus and pemphigoid.
AB  - Pemphigus and pemphigoid are characterized as autoimmune blistering diseases in
      which immunoglobulin G autoantibodies cause blisters and erosions of the skin or
      mucosa or both. Recently, understanding of the pathophysiology of pemphigus and
      pemphigoid has been furthered by genetic analyses, characterization of
      autoantibodies and autoreactive B cells, and elucidation of cell-cell adhesion
      between keratinocytes. For the management of pemphigus and pemphigoid, the
      administration of systemic corticosteroids still represents the standard
      treatment strategy; however, evidence of the efficacy of therapies not involving
      corticosteroids, such as those employing anti-CD20 antibodies, is increasing. The
      goal should be to develop antigen-specific immune suppression-based treatments.

PMID- 30228864
TI  - Recent advances in understanding corticotroph pituitary tumor initiation and
      progression.
AB  - Cushing's disease is the most frequent form of hypercortisolism and is caused by
      hypophyseal corticotroph adenomas secreting excessive amounts of
      adrenocorticotropic hormone. Most of the tumors develop sporadically and only a
      limited number of corticotroph adenomas have been found to be associated with
      different neuroendocrine syndromes or with familial isolated pituitary adenomas.
      The pathogenic mechanisms of corticotroph adenomas are largely unknown, but the
      discovered aberrant chaperoning activity of heat shock protein 90 on the one hand
      and the presence of ubiquitin-specific protease 8 mutations on the other hand
      partially explained the causes of their development. Corticotroph tumors arise
      initially as benign microadenomas but with time form invasively growing
      aggressive macroadenomas which can switch to corticotroph carcinomas in extremely
      rare cases. The mechanisms through which corticotroph tumors escape from
      glucocorticoid negative feedback are still poorly understood, as are the
      processes that trigger the progression of benign corticotroph adenomas toward
      aggressive and malignant phenotypes. This review summarizes recent findings
      regarding initiation and progression of corticotroph pituitary tumors.

PMID- 30228867
TI  - Recent advances in understanding and treating immunoglobulin light chain
      amyloidosis.
AB  - Immunoglobulin (Ig) light chain (AL) amyloidosis is a clonal plasma cell disorder
      characterized by misfolded Ig light chain deposition in vital organs of the body,
      resulting in proteotoxicity and organ dysfunction. Owing to its diverse clinical
      presentations and a tendency to mimic common medical conditions, AL amyloidosis
      is often diagnosed late and results in dismal outcomes. Early referral to a
      specialized center with expertise in management of AL amyloidosis is always
      recommended. The availability of sensitive biomarkers and novel therapies is
      reforming our approach to how we manage AL amyloidosis. Treatment for patients
      with AL amyloidosis should be risk-adapted and customized on the basis of
      individual patient characteristics. In the future, approaches directed at amyloid
      fibril clearance in combination with agents that target plasma cells will be
      needed both to eradicate the malignant clone and to establish organ responses.

PMID- 30228868
TI  - Recent advances in the management of gastric adenocarcinoma patients.
AB  - Gastric adenocarcinoma (GAC) is one of the most aggressive malignancies and has a
      dismal prognosis. Therefore, multimodality therapies to include surgery,
      chemotherapy, targeted therapy, immunotherapy, and radiation therapy are needed
      to provide advantage. For locally advanced GAC (>cT1B), the emerging strategies
      have included preoperative chemotherapy, postoperative adjuvant chemotherapy, and
      (occasionally) postoperative chemoradiation in various regions. Several novel
      therapies have been assessed in clinical trials, but only trastuzumab and
      ramucirumab (alone and in combination with paclitaxel) have shown overall
      survival advantage. Pembrolizumab has been approved by the US Food and Drug
      Administration on the basis of response rate only for patients with
      microsatellite instability (MSI-H) or if PD-L1 expression is positive (>=1%
      labeling index in tumor/immune cells in the presence of at least 100 tumor cells
      in the specimen). Nivolumab has been approved in Japan on the basis of a
      randomized trial showing significant survival advantage for patients who received
      nivolumab compared with placebo in the third or later lines of therapy. The cure
      rate of patients with localized GAC in the West is only about 40% and that for
      metastatic cancer is very poor (only 2-3%). At this stage, much more target
      discovery is needed through molecular profiling. Personalized therapy of patients
      with GAC remains a challenge.

PMID- 30228871
TI  - Understanding myocardial infarction.
AB  - Over the last 40 years, our understanding of the pathogenesis of myocardial
      infarction has evolved and allowed new treatment strategies that have greatly
      improved survival. Over the years, there has been a radical shift in therapy from
      passive healing of the infarction through weeks of bed rest to early discharge
      usually within 2 to 3 days as a result of immediate reperfusion strategies and
      other guideline-directed medical therapies. Nevertheless, challenges remain.
      Patients who develop cardiogenic shock still face a high 30-day mortality of at
      least 40%. Perhaps even more important is how do we identify and prevent patients
      from developing myocardial infarction in the first place? This article discusses
      these milestones of therapy and considers important issues for progress in the
      future.

PMID- 30228869
TI  - Blood Relatives: Splicing Mechanisms underlying Erythropoiesis in Health and
      Disease.
AB  - During erythropoiesis, hematopoietic stem and progenitor cells transition to
      erythroblasts en route to terminal differentiation into enucleated red blood
      cells. Transcriptome-wide changes underlie distinct morphological and functional
      characteristics at each cell division during this process. Many studies of gene
      expression have historically been carried out in erythroblasts, and the
      biogenesis of beta-globin mRNA-the most highly expressed transcript in
      erythroblasts-was the focus of many seminal studies on the mechanisms of pre-mRNA
      splicing. We now understand that pre-mRNA splicing plays an important role in
      shaping the transcriptome of developing erythroblasts. Recent advances have
      provided insight into the role of alternative splicing and intron retention as
      important regulatory mechanisms of erythropoiesis. However, dysregulation of
      splicing during erythropoiesis is also a cause of several hematological diseases,
      including beta-thalassemia and myelodysplastic syndromes. With a growing
      understanding of the role that splicing plays in these diseases, we are well
      poised to develop gene-editing treatments. In this review, we focus on changes in
      the developing erythroblast transcriptome caused by alternative splicing, the
      molecular basis of splicing-related blood diseases, and therapeutic advances in
      disease treatment using CRISPR/Cas9 gene editing.

PMID- 30228870
TI  - Low-dose hydroxycarbamide therapy may offer similar benefit as maximum tolerated
      dose for children and young adults with sickle cell disease in low-middle-income
      settings.
AB  - The multiple clinical benefits of hydroxycarbamide in sickle cell disease are
      supported by a large body of evidence. The maximum tolerated dose (MTD) is the
      regimen recommended by guidelines from a panel of National Heart, Lung, and Blood
      Institute (NHLBI) experts, but other dosage regimens have been used in babies
      (BABY-HUG) 9 to 18 months old (20 mg/kg per day) and developing countries such as
      India (10 mg/kg per day); however, there has been no direct comparison of the
      efficacy, effectiveness, or cost-effectiveness of these different regimens. The
      purpose of this review was to investigate the current situation with various
      hydroxycarbamide regimens with particular relevance to low-middle-income
      countries. In regard to methodology, a literature review was undertaken by using
      multiple databases in PubMed and Google and the search terms included sickle cell
      disease, hydroxyurea, hydroxycarbamide, sickle cell anaemia, low-middle-income
      countries, Sub-Saharan Africa, and India. Although MTD regimens have been widely
      used in research, especially within North America, clinical trials elsewhere tend
      to use fixed-dose regimens. In a survey of haematologists across Europe and
      Africa, 60% (75% response rate) did not use the MTD regimen for hydroxycarbamide
      treatment of sickle cell disease. The recommendations are (1) for practical
      purposes to commence using fixed-dose hydroxycarbamide in line with BABY-HUG
      recommendations and then (2) to consider or propose a trial comparing MTD
      escalation with various fixed doses and to include as end points health-related
      quality of life, haemoglobin F levels, adherence, and cost-effectiveness.

PMID- 30228874
TI  - A comparison of physical activity and nutrition in young women with and without
      primary dysmenorrhea.
AB  - Background: Dysmenorrhea is the most common gynecological disorder in young women
      and is seen in almost 50% of women. The present study was conducted to
      investigate the relationship between physical activity and nutrition with primary
      dysmenorrhea in students at Mazandaran University of Medical Sciences (Sari,
      Iran) in 2015. Methods: This comparative descriptive study was conducted on 250
      students with and without primary dysmenorrhea. Data were collected using
      personal-demographic, nutrition and physical activity questionnaires. The output
      was then analyzed in SPSS-18 using independent t-test, Chi-square test and
      logistic regression analysis. Results: The results showed significant differences
      between the two groups in terms of nutrition and physical activity, as the mean
      score of nutrition was 57.91 in the group with dysmenorrhea and 61.68 in the
      group without, while the mean intensity of physical activity was 5518.75 metric
      in the group with dysmenorrhea and 4666.42 metric in the group without. Physical
      activity was calculated by MET scale (minutes/week). This index measured the
      amount of consumed energy at the time of activity relative to that consumed at
      resting time. Conclusions: A healthier and more favorable nutrition style and
      more regular physical activity reduces the severity of dysmenorrhea in girls.
      Therefore, educational measures are required to raise awareness among young women
      about the effects of proper nutrition and physical activity on the prevention and
      reduction of dysmenorrhea complications.

PMID- 30228873
TI  - Recent Breakthroughs and Ongoing Limitations in Cryptosporidium Research.
AB  - The intestinal apicomplexan parasite Cryptosporidium is a major cause of
      diarrheal disease in humans worldwide. However, treatment options are severely
      limited. The search for novel interventions is imperative, yet there are several
      challenges to drug development, including intractability of the parasite and
      limited technical tools to study it. This review addresses recent, exciting
      breakthroughs in this field, including novel cell culture models, strategies for
      genetic manipulation, transcriptomics, and promising new drug candidates. These
      advances will stimulate the ongoing quest to understand Cryptosporidium and the
      pathogenesis of cryptosporidiosis and to develop new approaches to combat this
      disease.

PMID- 30228872
TI  - Recent advances in understanding the role of FOXO3.
AB  - The forkhead box O3 (FOXO3, or FKHRL1) protein is a member of the FOXO subclass
      of transcription factors. FOXO proteins were originally identified as regulators
      of insulin-related genes; however, they are now established regulators of genes
      involved in vital biological processes, including substrate metabolism, protein
      turnover, cell survival, and cell death. FOXO3 is one of the rare genes that have
      been consistently linked to longevity in in vivo models. This review provides an
      update of the most recent research pertaining to the role of FOXO3 in (i) the
      regulation of protein turnover in skeletal muscle, the largest protein pool of
      the body, and (ii) the genetic basis of longevity. Finally, it examines (iii) the
      role of microRNAs in the regulation of FOXO3 and its impact on the regulation of
      the cell cycle.

PMID- 30228875
TI  - Haematology of N'Dama and West African Short Horn cattle herds under natural
      Trypanosoma vivax challenge in Ghana.
AB  - Background: Animal trypanosomosis is a major cause of economic loss in livestock
      production in Africa. A suggested control measure is to use breeds with traits of
      trypanotolerance. The study examines the effect of natural Trypanosoma vivax
      challenge on haematological parameters in two trypanotolerant cattle [N'Dama and
      West African Short Horn (WASH)] herds. Methods:T. vivax-specific primers were
      used to diagnose T. vivax infection in an N'Dama herd at Cape Coast in southern
      Ghana and a WASH herd at Chegbani in northern Ghana from May to July 2011 in a
      cross-sectional study. Levels of haematological parameters comprising packed cell
      volume (PCV), haemoglobin (Hb) concentration and total red blood cell (RBC) and
      white blood cell (WBC) counts; differential WBC counts (neutrophils, lymphocytes,
      eosinophils, monocytes and basophils); and RBC indices of mean corpuscular volume
      (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin
      concentration (MCHC) were determined in blood samples and then compared between
      infected and uninfected cattle. Results: We found that haematological indices for
      infected and uninfected animals in both breeds were within the normal range.
      However, the mean PCV values for T. vivax-infected WASH and N'Dama were lower in
      infected compared to uninfected animals. The difference was significant ( p<
      0.05) in N'Dama but not in WASH. The RBC indices were higher in infected N'Dama
      compared to infected WASH with a significant difference in total RBC ( p < 0.05).
      Conclusion: We conclude from our findings that despite the presence of infection
      by T. vivax, N'Dama and WASH cattle maintained their haematological parameters
      within acceptable normal ranges, and this underscores the need for routine
      diagnosis and treatment so that such trypanotolerant cattle do not serve as
      potential reservoirs of trypanosome parasites.

PMID- 30228876
TI  - Predictive physiological anticipation preceding seemingly unpredictable stimuli:
      An update of Mossbridge et al's meta-analysis.
AB  - Background: This is an update of the Mossbridge et al's meta-analysis related to
      the physiological anticipation preceding seemingly unpredictable stimuli. The
      overall effect size observed was 0.21; 95% Confidence Intervals: 0.13 - 0.29
      Methods: Eighteen new peer and non-peer reviewed studies completed from January
      2008 to October 2017 were retrieved describing a total of 26 experiments and 34
      associated effect sizes. Results: The overall weighted effect size, estimated
      with a frequentist multilevel random model, was: 0.29; 95% Confidence Intervals:
      0.19-0.38; the overall weighted effect size, estimated with a multilevel Bayesian
      model, was: 0.29; 95% Credible Intervals: 0.18-0.39. Effect sizes of peer
      reviewed studies were slightly higher: 0.38; Confidence Intervals: 0.27-0.48 than
      non-peer reviewed articles: 0.22; Confidence Intervals: 0.05-0.39. The
      statistical estimation of the publication bias by using the Copas model suggest
      that the main findings are not contaminated by publication bias. Conclusions: In
      summary, with this update, the main findings reported in Mossbridge et al's meta
      analysis, are confirmed.

PMID- 30228878
TI  - Case Report: Root resorption caused after pulp death of adjacent primary molar.
AB  - Necrotic decayed primary molars with necrotic pulp tissues may show periapical
      involvement and root resorption. In this case report, a pediatric patient with a
      very common chief complain and clinical picture of necrotic badly decayed molar,
      introduced a very interesting case when radiographic investigation was performed,
      which showed that root resorption of the adjacent healthy molar occurred. The
      current report is, to the best of our knowledge, the first to report such finding
      in primary dentition.

PMID- 30228877
TI  - Analysis of the complete genome of hepatitis B virus subgenotype C2 isolate
      NHB17965 from a patient with uncomplicated chronicity.
AB  - The number of chronic cases of hepatitis B virus (HBV) is increasing rapidly in
      the world. Herein, we report a complete genome of HBV subgenotype C2 (HBV/C2)
      with current common amino acid substitutions from a patient with chronic HBV
      without liver complications. Complete genome analysis revealed that the isolated
      strain was a non-recombinant wild type and had several regular substitutions in
      the reverse transcriptase domain and small surface proteins of HBV. The isolated
      complete sequence could be considered as a chronic reference strain of HBV/C2 in
      Bangladesh. This study may help clinicians and scientists gain in-depth knowledge
      on common substitutions of HBV/C2 genome and to identify potential therapies
      against chronic HBV infections.

PMID- 30228880
TI  - Visualizing balances of compositional data: A new alternative to balance
      dendrograms.
AB  - Balances have become a cornerstone of compositional data analysis. However,
      conceptualizing balances is difficult, especially for high-dimensional data. Most
      often, investigators visualize balances with the balance dendrogram, but this
      technique is not necessarily intuitive and does not scale well for large data.
      This manuscript introduces the 'balance' package for the R programming language.
      This package visualizes balances of compositional data using an alternative to
      the balance dendrogram. This alternative contains the same information coded by
      the balance dendrogram, but projects data on a common scale that facilitates
      direct comparisons and accommodates high-dimensional data. By stripping the
      branches from the tree, 'balance' can cleanly visualize any subset of balances
      without disrupting the interpretation of the remaining balances. As an example,
      this package is applied to a publicly available meta-genomics data set measuring
      the relative abundance of 500 microbe taxa.

PMID- 30228879
TI  - Relationship between levels of the heavy metals lead, cadmium and mercury, and
      metallothionein in the gills and stomach of Crassostrea iredalei and Crassostrea
      glomerata.
AB  - Background: The objective of this study was to compare the levels of heavy metals
      (Pb, Hg, and Cd) and metallothionein (MT) in the gills and stomach of two species
      of mussels ( Crassostrea iredalei and Crassostrea glomerata), and to observe the
      ability of the mussels to absorb the heavy metals Pb, Hg and Cd present in the
      water. Methods: The mussels were obtained from Mayangan, Kenjeran and Gresik
      ports, East Java, Indonesia. MT levels were determined using ELISA. Heavy metal
      levels of Pb, Hg and Cd were assayed using atomic absorption spectrophotometry.
      Results: The levels of Pb and Cd in water were below the maximum permissible
      levels for local water quality standards. By contrast, the level of Hg in the
      water was above the maximum permissible levels for water quality standards. At
      Mayangan Port (Station 1), the level of Pb was higher than Hg and Cd. Levels of
      MT and heavy metals varied greatly among of C. iredalei and C. glomerata
      individuals, but were always higher in the gills than in the stomach. The highest
      MT level (160,250 ng/g) was observed at Kenjeran Port (Station 2). MT levels were
      shown to be significantly associated with heavy metal level ( P<0.0001).
      Conclusions: This result indicates that MT may be responsible for the
      sequestration of these heavy metals, as has already been observed in terrestrial
      animals.

PMID- 30228881
TI  - Comparison of clustering tools in R for medium-sized 10x Genomics single-cell RNA
      sequencing data.
AB  - Background: The commercially available 10x Genomics protocol to generate droplet
      based single-cell RNA-seq (scRNA-seq) data is enjoying growing popularity among
      researchers. Fundamental to the analysis of such scRNA-seq data is the ability to
      cluster similar or same cells into non-overlapping groups. Many competing methods
      have been proposed for this task, but there is currently little guidance with
      regards to which method to use. Methods: Here we use one gold standard 10x
      Genomics dataset, generated from the mixture of three cell lines, as well as
      three silver standard 10x Genomics datasets generated from peripheral blood
      mononuclear cells to examine not only the accuracy but also robustness of a dozen
      methods. Results: We found that some methods, including Seurat and Cell Ranger,
      outperform other methods, although performance seems to be dependent on the
      complexity of the studied system. Furthermore, we found that solutions produced
      by different methods have little in common with each other. Conclusions: In light
      of this, we conclude that the choice of clustering tool crucially determines
      interpretation of scRNA-seq data generated by 10x Genomics. Hence practitioners
      and consumers should remain vigilant about the outcome of 10x Genomics scRNA-seq
      analysis.

PMID- 30228883
TI  - Use of checkpoint inhibitors in liver transplant recipients.
AB  - In spite of their major impact in cancer therapy, immune checkpoint inhibitors
      are considered to be contraindicated in liver transplant recipients due to fear
      of rejection and fatal liver failure. Nevertheless, an increasing number of
      instances of liver transplant recipients treated with checkpoint inhibitors is
      being published. We reviewed the reports on 14 known cases of liver transplant
      recipients who underwent treatment with checkpoint inhibitors and discuss factors
      likely to determine susceptibility to organ rejection including the choice of the
      agent and the immunosuppression employed, the assessment of Programmed cell death
      1 ligand 1 (PD-L1) status in liver graft biopsies, and the time of treatment
      initiation.

PMID- 30228882
TI  - Enteroscopy in children.
AB  - Introduction: Device-assisted enteroscopy is a new endoscopic technique for the
      evaluation of small bowel in adults and children. Data in pediatric population
      are limited. This review aims to identify diagnostic and therapeutic benefits of
      enteroscopy in children. Methods: We have analysed paediatric literature on
      device-assisted enteroscopy focusing on indications, technical aspects and
      complications, with attention given to adult publications that may be applicable
      to the paediatric population. Results: Obscure gastrointestinal bleeding, Crohn's
      disease and small bowel polyps are the main indications of enteroscopy in
      children. Device-assisted enteroscopy has high diagnostic yield for the main
      paediatric indications, but MR-enterography and capsule endoscopy should be used
      beforehand in diagnostic work-up to better identify candidates for enteroscopy
      and to improve its diagnostic and therapeutic yield. Major complications are rare
      and mostly related to therapeutic procedures. Conclusion: Despite limited data in
      the paediatric population, device-assisted enteroscopy represents a useful and
      safe endoscopic technique in children. Its use, combined with MR-enterography and
      capsule endoscopy, allows identification and treatment of many of the small bowel
      paediatric diseases with a low risk of complications.

PMID- 30228884
TI  - Foreign body ingestion and food impaction in adults: better to scope than to
      wait.
AB  - Background and objective: To assess clinical outcomes after foreign body
      ingestion and food impaction; to identify predictors of foreign body presence at
      the time of endoscopy. Methods: A prospective study including consecutive adult
      patients with foreign body ingestion or suspected food impaction between May 2014
      and August 2016. Results: In total, 521 patients were included, 320 with foreign
      body ingestion and 201 with suspected food impaction. Food impaction patients
      were significantly older and more frequently had a history of oesophageal
      disease. The foreign body was encountered in the upper digestive tract in 43% of
      the patients with foreign body ingestion, and food impaction was confirmed in
      87%. Older age (odds ratio (OR)year 1.04, 95% confidence interval (CI) 1.02-1.06)
      and early presentation (ORfirst six hours 4.41, 95% CI 2.24-8.66) were
      independent predictors of foreign body presence, while a history of psychiatric
      disease was an independent predictor of food impaction (OR 6.69, 95% CI 1.66
      26.9). Successful endoscopic treatment was achieved in more than 90% of the
      cases, with adverse events occurring in fewer than 5%. Foreign body forceps was
      the preferred device in foreign body ingestion, while retrieval basket and
      mobilisation were preferred in food impaction. The need to use more than one
      instrument was significantly higher in food impaction. Conclusion: Foreign bodies
      are encountered at endoscopy in almost half of the cases. Older age and earlier
      presentation are independent predictors of its presence. Given the high
      proportion of patients with foreign body at endoscopy and the low risk of
      complications, endoscopic evaluation is probably justified in the majority of
      cases.

PMID- 30228885
TI  - High-resolution manometry is superior to endoscopy and radiology in assessing and
      grading sliding hiatal hernia: A comparison with surgical in vivo evaluation.
AB  - Background: Hiatal hernia is diagnosed by barium-swallow esophagogram or
      esophagogastroduodenoscopy, with possible suboptimal results. High-resolution
      manometry clearly identifies crural diaphragm and lower esophageal sphincter.
      Objectives: To assess the diagnostic accuracy of high-resolution manometry in
      detecting hiatal hernia compared to esophagogram and esophagogastroduodenoscopy,
      using as reference the surgical in vivo measurement. Methods: Patients were
      studied with esophagogram, esophagogastroduodenoscopy, high-resolution manometry
      and in vivo evaluation of the esophago-gastric junction. Esophago-gastric
      junction was classified as type I (no separation between crural diaphragm and
      lower esophageal sphincter); type II (>=1, <= 2 cm separation); type III (>2 cm).
      During in vivo measurement, distance between the esophago-gastric junction and
      crural diaphragm proximal border was recorded. Results: Surgery identified 53
      hiatal hernias in 100 patients. Forty-seven percent were classified as type I
      esophago-gastric junction, 35% type II and 18% type III. Referenced to in vivo
      evaluation, high-resolution manometry showed superior diagnostic sensitivity and
      specificity (94.3% and 91.5%, respectively) to esophagogram and
      esophagogastroduodenoscopy, with 92.6% predictive value of a positive test and
      93.5% predictive value of a negative test. The kappa value for high-resolution
      manometry and in vivo evaluation was 0.85. High-resolution manometry showed
      optimal sensitivity and specificity in detecting types I, II and III esophago
      gastric junction. Conclusions: High-resolution manometry enables an accurate
      diagnosis of hiatal hernia and a better classification than endoscopy and
      radiology, reaching optimal agreement with in vivo assessment.

PMID- 30228886
TI  - A single-step sizing and radiofrequency ablation catheter for circumferential
      ablation of Barrett's esophagus: Results of a pilot study.
AB  - Background: The 360 Express balloon catheter (360 Express) has the ability to
      self-adjust to the esophageal lumen, ensuring optimal tissue contact. Objective:
      The objective of this article is to evaluate the efficacy and safety of the 360
      Express for radiofrequency ablation (RFA) treatment of Barrett's esophagus (BE).
      Methods: BE patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD)
      or early cancer (EC) were included. Visible lesions were removed by endoscopic
      resection (ER) prior to RFA. RFA was performed with the 360 Express using the
      standard ablation regimen (12J/cm2-clean-12J/cm2). Primary outcome: BE regression
      percentage at three months. Secondary outcomes: procedure time, adverse events,
      complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM).
      Results: Thirty patients (median BE C4M6) were included. Eight patients underwent
      ER prior to RFA. Median BE regression: 90%. Median procedure time: 31 minutes.
      Adverse events (13%): laceration (n = 1); atrial fibrillation (n = 1); vomiting
      and dysphagia (n = 1); dysregulated diabetes (n = 1). After subsequent treatment
      CE-D and CE-IM was achieved in 97% and 87%, respectively. In 10% a stenosis
      developed during additional treatment requiring a median of one dilation.
      Conclusion: This study shows that circumferential RFA using the 360 Express may
      shorten procedure time, while maintaining efficacy compared to standard
      circumferential RFA.

PMID- 30228887
TI  - Giant gastric ulcers: Malignancy yield and predictors from a 10-year
      retrospective single centre cohort.
AB  - Background and study aims: Gastric cancer is known to reside in some gastric
      ulcers but what predicts this association is still unclear. Historically it has
      been thought that the increasing size of gastric ulcers may be a predictor for
      harbouring malignancy. Giant gastric ulcers are arbitrarily defined as >=3 cm.
      The aim of this retrospective study was to examine patients with giant gastric
      ulcers within a single tertiary centre over a 10-year period. Our primary
      outcomes included the malignancy yield in giant gastric ulcers and to determine
      if any demographic, clinical or endoscopic predictors for malignancy exist.
      Secondary outcomes included the 30-day and 12-month mortality. Method: Patients
      with giant gastric ulcers >=3 cm presenting from September 2005 to December 2015
      were included in the study. Malignancy yield was obtained by looking at histology
      reports. Predictors for malignancy were tested using binary logistic regression,
      after demographic, clinical and endoscopic variables were tested using univariate
      analysis and for collinearity. Results: A cohort of 111 patients was included for
      the final analysis. Forty-two giant gastric ulcers were malignant, equating to a
      yield of 37.8% (95% CI 28.8-46.8). Binary logistic regression revealed predictors
      for malignancy included: ulcer location being within the fundus, cardia or
      incisura (odds ratio (OR) 4.417; 95% CI 1.10-17.76; P = 0.036); younger age of
      patient (OR 0.202; 95% CI 0.06-0.71; P = 0.013); and endoscopic 'non-suspicion'
      (OR 0.138; 95% CI 0.049-0.39; P < 0.001). Patient's 12-month mortality for giant
      gastric ulcer was 61.9% (26/42) for malignant and 21.9% (11/73) for benign
      histology. Conclusion: We have shown a high malignancy yield of 37.8% (95% CI
      28.8-46.8) and a 12-month mortality of 61.9% for malignant giant gastric ulcers
      and 21.9% for benign giant gastric ulcers. Predictors for malignancy in patients
      with giant gastric ulcers include ulcer location, patient's age and endoscopist's
      'suspicion' during endoscopy.

PMID- 30228889
TI  - Endoscopic full-thickness resection of duodenal lesions-a retrospective analysis
      of 20 FTRD cases.
AB  - Background: Endoscopic resections in the duodenum harbor a significant risk of
      complications. The full-thickness resection device (FTRD) has shown favorable
      results concerning efficacy and safety in the resection of colorectal lesions.
      Data of its use in the duodenum are limited to a single, small case series (n =
      4). Methods: Data of all consecutive patients scheduled for endoscopic full
      thickness resection (EFTR) of duodenal lesions by FTRD in our institution were
      collected and analyzed retrospectively. Primary endpoint was technical success.
      Results: Between March 2014 and June 2017 EFTR of a duodenal lesion was planned
      in a total of 20 patients. Overall technical success was 17/20 (85.0%).
      Indication for EFTR was: adenomas (n = 13, seven treatment naive, six
      pretreated), subepithelial tumors (n = 5) and T1 adenocarcinoma (n = 1). The FTRD
      could be advanced to the lesion in 19/20 cases (95.0%). R0-resection rate was
      12/19 (63.2%). During follow-up after 3 and 12 months there were two recurrent
      adenomas that were successfully re-resected by FTRD. Minor bleedings occurred at
      the first postinterventional day in 3/19 (15.8%). There were no major bleedings
      and perforations. Conclusion: This study confirmed the feasibility of duodenal
      EFTR and indicates good efficacy and safety. Larger studies are needed to further
      investigate this novel technique.

PMID- 30228888
TI  - The Vampire Study: Significant elevation of faecal calprotectin in healthy
      volunteers after 300 ml blood ingestion mimicking upper gastrointestinal
      bleeding.
AB  - Background: Faecal calprotectin correlates with histological and clinical
      activity in inflammatory bowel disease. Gastrointestinal bleeding might also
      increase faecal calprotectin levels, erroneously implying intestinal
      inflammation; however, this possibility has not been systematically assessed.
      Methods: Sixteen healthy volunteers without gastrointestinal disease and normal
      faecal calprotectin baseline values ingested their own blood twice, either by
      drinking or via nasogastric tube. Quantities of 100 ml and 300 ml blood were
      ingested in a randomised order, with a 28-day wash-out period. Faecal
      calprotectin, faecal occult blood test, and the occurrence of melaena were
      assessed. Faecal calprotectin >= 50 ug/g was considered elevated. Results:
      Melaena was reported by all healthy volunteers after 300 ml and by 11/15 healthy
      volunteers (71%) after 100 ml blood ingestion. One day after ingestion of 300 ml
      blood, 8/16 faecal calprotectin tests were positive compared to 1/16 at baseline
      (p = 0.016). Faecal calprotectin levels above > 200 ug/g were rarely observed.
      There was a trend for faecal calprotectin test positivity also after ingestion of
      100 ml. Conclusion: Ingestion of blood resulted in an increase in faecal
      calprotectin-positive tests. Gastrointestinal bleeding should be considered as a
      potential cause of mild faecal calprotectin elevation > 50 ug/g; however,
      increased faecal calprotectin above > 250-300 ug/g, the established cut-off for
      relevant intestinal inflammation in patients with inflammatory bowel disease, is
      rare.

PMID- 30228890
TI  - Long-term health and treatment outcomes in adult coeliac disease patients
      diagnosed by screening in childhood.
AB  - Background: The diagnostic yield of coeliac disease could be improved by
      screening in at-risk groups, but long-term benefits of this approach are obscure.
      Objective: To investigate health, quality of life and dietary adherence in adult
      coeliac patients diagnosed in childhood by screening. Methods: After thorough
      evaluation of medical history, follow-up questionnaires were sent to 559 adults
      with a childhood coeliac disease diagnosis. The results were compared between
      screen-detected and clinically-detected patients, and also between originally
      asymptomatic and symptomatic screen-detected patients. Results: In total, 236
      (42%) patients completed the questionnaires a median of 18.5 years after
      childhood diagnosis. Screen-detected patients (n = 48) had coeliac disease in the
      family and type 1 diabetes more often, and were less often smokers and members of
      coeliac societies compared to clinically-detected patients, whereas the groups
      did not differ in current self-experienced health or health concerns, quality of
      life or dietary adherence. Screen-detected, originally asymptomatic patients had
      more anxiety than those presenting with symptoms, whereas the subgroups were
      comparable in other current characteristics. Conclusion: Comparable long-term
      outcomes between screen-detected and clinically-detected patients support risk
      group screening for coeliac disease. However, asymptomatic patients may require
      special attention.

PMID- 30228891
TI  - Real-world management of juvenile autoimmune liver disease.
AB  - Background and aims: Juvenile autoimmune liver disease (JAILD) includes
      paediatric forms of autoimmune hepatitis (AIH) and autoimmune sclerosing
      cholangitis (ASC). Since evidence is scarce, there are currently no evidence
      based management guidelines for juvenile AIH. This survey was carried out amongst
      the paediatric members of the International AIH Group (IAIHG) to describe their
      practices in the management of JAILD. Methods: An online survey questionnaire was
      distributed to members of the IAIHG with active practice
      (https://www.surveymonkey.de/r/Juvenile_AILD). The questionnaire consisted of
      four clinical scenarios on different presentations of AIH. Results: Fifty-eight
      surveys were sent to the IAIHG members, out of which 43 (74%, 22 countries, four
      continents) were returned. None reported budesonide as a first-line induction
      agent for the acute presentation of AIH. Sixteen (37%) routinely perform liver
      biopsy at three years of biochemical remission. Thirty-five respondents (81%)
      perform magnetic resonance cholangiography (MRC) at presentation. Ciclosporin is
      the most widely used second-line agent (number of patients treated = ~360, 21
      centres). Mycophenolate mofetil (n = ~225, 31 centres), tacrolimus (n = ~130, 21
      centres) and sirolimus (n = ~5, 3 centres) are less often reported. Rescue
      therapy with infliximab and rituximab has been tried in eight centres (n = ~19)
      and nine centres (n = ~16), respectively. Conclusions: Prednisolone remains the
      preferred first-line induction agent in JAILD. MRC at presentation is performed
      by the large majority of participants. Participants reported a wide variation in
      performing liver biopsy for therapy evaluation during follow-up. Within the
      paediatric members of the IAIHG there is considerable experience with second-line
      therapeutic agents.

PMID- 30228892
TI  - Sarcopenia is associated with reduced survival in patients with advanced
      hepatocellular carcinoma undergoing sorafenib treatment.
AB  - Background: Sarcopenia has been associated with poor outcomes in patients with
      cirrhosis and solid tumours. Objective: Analyse the influence of sarcopenia on
      survival and treatment duration in patients with advanced hepatocellular
      carcinoma (HCC) treated with sorafenib. Methods: We conducted a multicentre,
      retrospective study on 96 patients with advanced HCC treated with sorafenib, all
      with available abdominal computed tomography (CT) scan within 30 days from
      treatment start. Anthropometric, laboratory, treatment and follow-up data were
      collected. Sarcopenia was defined by reduced skeletal muscle index calculated
      from an L3 section CT image. Results: Sarcopenia was present in 49% of patients.
      Patients were divided into two groups according to sarcopenia: age was
      significantly higher in the sarcopenic group (SG) (66 years (31-87) versus 72
      years (30-84), p = 0.04], with no difference in other baseline characteristics.
      The SG showed shorter overall survival (OS) (39 (95% confidence interval (CI) 26
      50) versus 61 (95% CI 47-77) weeks (p = 0,01)) and shorter time on treatment
      (12.3 (95% CI 8-19) versus 25.9 (95% CI 15-33) weeks (p = 0.0044)). At
      multivariate analysis, sarcopenia was independently associated to reduced OS (p =
      0.03) and reduced time on treatment (p = 0.001). Conclusion: Sarcopenia is
      present in almost half of patients with advanced HCC, and is associated with
      reduced survival and reduced duration of oral chemotherapy.

PMID- 30228893
TI  - Impact of nutritional status on pulmonary function after lung transplantation for
      cystic fibrosis.
AB  - Background: Nutritional status is an important prognostic factor in patients with
      cystic fibrosis (CF) prior to lung transplantation. Objective: To investigate the
      impact of nutritional status on pulmonary function in CF transplant recipients.
      Methods: Adult double lung transplanted CF patients were consecutively included.
      The predictive value of nutritional status on lung function - measured by
      spirometry - was longitudinally assessed by body composition serially evaluated
      by a three-compartment model bioelectrical impedance analysis (BIA) in comparison
      to body mass index (BMI). Results: Overall, 147 spirometries and 147 BIAs were
      performed in 58 patients (59% female, median age: 30.1 years, median BMI: 19.6
      kg/m2). Malnourished patients (BMI < 18.5 kg/m2; 27.6%) had a significantly
      reduced lung function compared to normal/overweight patients (forced expiratory
      volume in 1 second in percent (FEV1%pred), 57% vs 77%; p = 0.024). BMI, as well
      as the BIA parameters phase angle, total body water, fat free mass, body cell
      mass (BCM) and extracellular mass (ECM)/BCM ratio, were univariate predictors of
      FEV1%pred. When included in a linear mixed model, ECM/BCM ratio remained the only
      significant predictor of lung function (p = 0.012). Conclusion: Nutritional
      status assessed by BIA predicted lung function in CF transplant recipients.
      Serial BIA measurements to monitor patients' nutritional status might help to
      improve or maintain lung function.

PMID- 30228894
TI  - Dietary supplementation of vitamin D prevents the development of western diet
      induced metabolic, hepatic and cardiovascular abnormalities in rats.
AB  - Background: The western diet high in fat and fructose may cause metabolic
      disorders and cardiovascular diseases. Objective: To evaluate whether long-term
      daily vitamin D3 supplementation prevents hepatic steatosis and cardiovascular
      abnormalities and restores insulin sensitivity caused by fat diet in rats without
      vitamin D deficiency. Methods: Three groups of rats were fed for 6 months with
      standard diet (SD), western diet (WD) or WD containing 23 IU/day/rat vitamin D3,
      respectively. Tail-cuff systolic blood pressure (SBP)measurements in conscious
      rats and transthoracic echocardiography were performed in basal condition, and
      after 3 and 6 months of diet. Hepatic steatosis and myocardial fibrosis were
      assessed in liver and cardiac tissues using standard methods. Serum insulin and
      25(OH)D3 concentrations were determined using rat-specific ELISA kits. Insulin
      resistance was determined according to the homeostasis model assessment of
      insulin resistance (HOMA-IR) method. Results: Sixty-one per cent of hepatocytes
      in WD rats had steatotic vacuoles compared with just 27% in rats on a WD plus
      vitamin D3 (p < 0.05).HOMA-IR was reduced in rats with vitamin D supplementation
      compared with WD alone (19.4 +/- 5.2 vs 41.9 +/- 8.9, p < 0.05). Rat blood
      pressure and left ventricular mass were both reduced by vitamin D3
      supplementation. Conclusion: In animal models of liver and cardiovascular
      metabolic damage, the supplementation of vitamin D3 shows liver and cardio
      protective effects.

PMID- 30228895
TI  - Submucosal fat accumulation in human colorectal tissue and its association with
      abdominal obesity and insulin resistance.
AB  - Background: In addition to visceral fat, peripheral ectopic fat accumulation is
      suggested to play a role in the pathophysiology of metabolic syndrome, which is
      known to be associated with not only cardiovascular diseases and type 2 diabetes
      mellitus but also colorectal cancer. Objective: This study aims to clarify
      whether there is ectopic fat accumulation in human colorectal tissue in
      association with metabolic syndrome or its components such as abdominal obesity
      and insulin resistance. Methods: Lipid contents of colorectal tissue were
      measured in 27 patients with colorectal polyp excised endoscopically. In
      addition, lipid droplets were immunohistochemically estimated using anti
      perilipin antibody in 32 patients with colorectal cancer resected surgically.
      Results: Increasing tissue triglyceride/phospholipid ratio was associated with
      increasing body mass index, fasting plasma insulin level and homeostasis model
      assessment as an index of insulin resistance (HOMA-IR), and also decreasing serum
      adiponectin level. Lipid droplets were observed in the submucosal region of
      colorectal tissue. The amount of lipid droplets was associated with increasing
      body mass index, waist circumference and visceral fat area. Conclusion: This
      study showed the presence of submucosal fat accumulation in human colorectal
      tissue and its association with abdominal obesity and insulin resistance.

PMID- 30228896
TI  - An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary
      response to infliximab in inflammatory bowel disease patients.
AB  - Background: Predicting the response of inflammatory bowel disease (IBD) patients
      to infliximab (IFX) is an unmet clinical need. The expression and density of
      transmembrane tumor necrosis factor-alpha in circulating leukocytes maybe
      directly related to response by promoting apoptosis. Aim: We tested the
      hypothesis that direct apoptosis assessment by real-time polymerase chain
      reaction evaluation of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins in
      peripheral blood mononuclear cells (PBMCs) might be associated with response to
      IFX. Methods: IFX naive patients (Crohn's disease, 32 and ulcerative colitis, 20;
      35 responders and 17 non-responders) were evaluated for Bax and Bcl-2 mRNA
      expression levels before and 2 weeks after the first infusion. In a subset of
      patients, apoptosis was also evaluated using flow cytometry. Results: After the
      first infusion, Bax increased more in responders than in non-responders (0.7+/-
      0.38 vs 0.81 +/- 0.32 and 0.86 +/- 0.37 vs 0.87 +/- 0.45, respectively, p =
      0.071). Bcl-2 decreased more in responders than in non-responders (0.71 +/- 0.12
      vs 0.63 +/- 0.13 and 0.81 +/- 0.28 vs 0.77 +/- 0.27, respectively, p = 0.038).
      The Bax/Bcl-2 ratio increased more in responders than in non-responders (0.99 +/-
      0.5 vs 1.3 +/- 0.51 and 1.03 +/- 0.17 vs 1.1 +/- 0.28, respectively, p = 0.005).
      The Bax/Bcl-2 ratio was able to predict response in 33/52 patients and was
      correlated to flow cytometry-assessed apoptosis (r = 0.911; p < 0.001).
      Conclusions: An increased Bax/Bcl-2 ratio in PBMCs was associated with
      therapeutic response to IFX in IBD patients.

PMID- 30228897
TI  - Individual invitation letters lead to significant increase in attendance for
      screening colonoscopies: Results of a pilot study in Northern Hesse, Germany.
AB  - Background: Colorectal cancer (CRC) is the second most common cancer in Germany.
      Screening colonoscopies are considered an effective tool for early detection and
      prevention of CRC and are recommended in Germany for citizens over the age of 55.
      To increase the participation rate for screening colonoscopies, an invitation
      procedure was initiated in parts of Germany for patients between the ages of 55
      and 75 who had never undergone a screening colonoscopy before. Methods: We
      examined the number of participating patients before, during, and after the
      invitation procedure and compared the number of the participating patients who
      received a cover letter with the participating patients from the control group.
      Additionally, we classified the findings of the colonoscopies including CRC,
      advanced adenomas, and polyps. Results: During the invitation period, the
      participation rate of the invitation group increased from 220 patients to 531
      patients compared to 1256 to 1693 in the control group. The increase was
      significantly greater in patients with cover letters (+141% vs.+35%, p < 0.0001).
      Also, significantly more polyps and adenomas were found in patients from the
      invitation letter group (254 (+102%) vs. 679 (-9%), p < 0.0001). Conclusions: Our
      study clearly indicates that personal invitation letters are an effective measure
      to increase overall participation rates in screening colonoscopies.

PMID- 30228898
TI  - Carbon dioxide insufflation during endoscopic resection of large colorectal
      polyps can reduce post-procedure abdominal pain: A prospective, double-blind,
      randomized controlled trial.
AB  - Background: Studies of the use of CO2 insufflation during endoscopic resection of
      large colorectal polyps (LCPs) are lacking. Objective: We evaluated the effect of
      CO2 insufflation on pain after endoscopic resection of LCPs. Methods: In a
      prospective randomized controlled trial (RCT), 132 patients were randomly
      assigned to groups who underwent endoscopic resection with CO2 insufflation (CO2
      group, n = 66) or air insufflation (air group, n = 66). The primary outcome was
      abdominal pain post-procedure (PP). The secondary outcomes were abdominal
      distension, rates of technical success, amounts of sedatives prescribed, use of
      analgesics, and adverse events. Results: Baseline patient characteristics were
      similar between the groups. The mean abdominal pain score was 12.3 in the CO2
      group vs. 17.5 in the air group at 1 h PP (p  =  0.047). Also, the proportion of
      patients without pain was significantly higher in the CO2 group at 1 h PP (p =
      0.008). The pain score differed more in the endoscopic submucosal dissection
      group and long-time group. The secondary outcomes were not significantly
      different between the two groups. Conclusions: The results of this RCT
      demonstrate the superiority of CO2 insufflation for endoscopic resection of LCPs
      in terms of decreasing PP abdominal pain (KCT0001636).

PMID- 30228899
TI  - Leaving colorectal polyps in place can be achieved with high accuracy using blue
      light imaging (BLI).
AB  - Objectives: A negative predictive value of more than 90% is proposed by the
      American Society of Gastrointestinal Endoscopy Preservation and Incorporation of
      Valuable Endoscopic Innovations (PIVI) statement for a new technology in order to
      leave distal diminutive colorectal polyps in place without resection. To our
      knowledge, no prior prospective study has yet evaluated the feasibility of the
      most recently introduced blue light imaging (BLI) system for real-time endoscopic
      prediction of polyp histology for the specific endpoint of leaving hyperplastic
      polyps in place. Aims: Prospective assessment of real-time prediction of
      colorectal polyps by using BLI. Material and methods: In total, 177 consecutive
      patients undergoing screening or surveillance colonoscopy were included.
      Colorectal polyps were evaluated in real-time by using high-definition endoscopy
      and the BLI technology without optical magnification. Before resection, the
      endoscopist described each polyp according to size, shape and surface
      characteristics (pit and vascular pattern, colour and depression), and histology
      was predicted with a level of confidence (high or low). Results: Histology was
      predicted with high confidence in 92.5% of polyps. Sensitivity of BLI for
      prediction of adenomatous histology was 92.68%, with a specificity and accuracy
      of 94.87 and 93.75%, respectively. Following the recommendation of the PIVI
      statement, positive and negative predictive values were calculated with values of
      95 and 92.5%, respectively. Prediction of surveillance based on both US and
      European guidelines was correctly predicted in 91% of patients. Conclusion: The
      most recently introduced BLI technology is accurate enough to leave distal
      colorectal polyps in place without resection. BLI also allowed for assignment of
      postpolypectomy surveillance intervals. This approach therefore has the potential
      to reduce costs and risks associated with the redundant removal of diminutive
      colorectal polyps.

PMID- 30228900
TI  - Adoption of colonoscopy quality measures across Europe: the European Colonoscopy
      Quality Investigation (ECQI) Group experience.

PMID- 30228901
TI  - Adoption of colonoscopy quality measures across Europe by Riemann et al.

PMID- 30228902
TI  - Young GI angle: How to chair a session.

PMID- 30228903
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1177/2050640618756124.].

PMID- 30228904
TI  - Prognostic value of routinely available data in patients with stable coronary
      heart disease. A 10-year follow-up of patients sampled at random times during
      their disease course.
AB  - Objective: To characterise the long-term prognosis of patients with stable
      coronary artery heart disease by means of 'standard predictors' defined as
      demographic, clinical and biochemical quantities routinely available in general
      practices and ascertained at an interview not prompted by renewed cardiac
      complaints. Methods: This is an observational study based on data from 2199
      Copenhagen placebo patients from the 'clarithromycin for patients with stable
      coronary heart disease' trial of patients with stable coronary heart disease. In
      the trial, we compared the effects of 14 days of clarithromycin treatment versus
      placebo. The predictors were based on the interview forms and blood samples
      collected at entry, along with demographic information from hospital files.We
      studied 'standard predictors' of a composite outcome (myocardial infarction,
      unstable angina, cerebrovascular disease or all-cause death) and of all-cause
      death. Using Cox regression, we compared predictions of status at 3, 6 and 9
      years without and with the use of 'standard predictors' and used receiver
      operating characteristic statistic. Results: Few 'standard predictors' were
      associated (p<0.01) with the composite outcome or with all-cause death. When no
      'standard predictors' were included, 63.2% of the model-based predictions of the
      composite outcome and 79.9% of death predictions were correct. Including all
      'standard predictors' in the model increased the figures to 68.4% and 83.4%,
      respectively. C indices were low, except when all-cause death was assessed as a
      single outcome where C was 0.79. Conclusion: 'Standard predictors' routinely
      available in general practices contribute only modestly to risk assessment in
      consecutively sampled patients with stable coronary heart disease as ascertained
      at a contact not prompted by renewed cardiac complaints. Novel biomarkers may
      improve the assessment. Trial registration number: NCT00121550.

PMID- 30228905
TI  - Mortality after admission for heart failure in the UK compared with Japan.
AB  - Objective: Mortality amongst patients hospitalised for heart failure (HHF) in
      Western and Asian countries may differ, but this has not been investigated using
      individual patient-level data (IPLD). We sought to remedy this through rigorous
      statistical analysis of HHF registries and variable selection from a systematic
      literature review. Methods and results: IPLD from registries of HHF in Japan
      (n=3781) and the UK (n=894) were obtained. A systematic literature review
      identified 23 models for predicting outcome of HHF. Five variables appearing in
      10 or more reports were strongly related to prognosis (systolic blood pressure,
      serum sodium concentration, age, blood urea nitrogen and creatinine). To compare
      mortality in the UK and Japan, variables were imputed in a propensity model using
      inverse probability of treatment weighting (IPTW) and IPTW with logistic
      regression (doubly robust IPTW). Overall, patients in the UK were sicker and in
      patient and post-discharge mortalities were greater, suggesting that the
      threshold for hospital admission was higher. Covariate-adjusted in-hospital
      mortality was similar in the UK and Japan (IPTW OR: 1.14, 95% CI 0.70 to 1.86),
      but 180-day postdischarge mortality was substantially higher in the UK (doubly
      robust IPTW OR: 2.33, 95% CI 1.58 to 3.43). Conclusions: Despite robust methods
      to adjust for differences in patient characteristics and disease severity, HHF
      patients in the UK have roughly twice the mortality at 180 days compared with
      those in Japan. Similar analyses should be done using other data sets and in
      other countries to determine the consistency of these findings and identify
      factors that might inform healthcare policy and improve outcomes.

PMID- 30228906
TI  - Cardiologist perceptions of family-centred rounds in cardiovascular clinical
      care.
AB  - Objective: Few data exist regarding physician attitudes and implementation of
      family-centred rounds (FCR) in cardiovascular care. This study aimed to assess
      knowledge and attitudes among cardiologists and cardiology fellows regarding
      barriers and benefits of FCRs. Methods: An electronic, web-based questionnaire
      was nationally distributed to cardiology fellows and attending cardiologists.
      Results: In total, 118 subjects were surveyed, comprising cardiologists (n=64,
      54%) and cardiology fellows (n=54, 46%). Overall, 61% of providers reported
      participating in FCRs and 64% felt family participation on rounds benefits the
      patient. Both fellows and cardiologists agreed that family rounds eased family
      anxiety (fellows, 63%; cardiologists, 56%; p=0.53), improved communication
      between the medical team and the patient and family (fellows, 78%; cardiologists,
      61%; p=0.18) and improved patient safety (fellows, 59%; cardiologists, 47%;
      p=0.43). Attitudes regarding enhancement of trainee education were similar
      (fellows, 69%; cardiologists, 55%; p=0.19). Fellows and cardiologists felt that
      family increased the duration of rounds (fellows, 78%; cardiologists, 80%;
      p=0.18) and led to less efficient rounds (fellows, 54%; cardiologists, 58%;
      p=0.27). Conclusion: The majority of cardiologists and fellows believed that FCRs
      benefited families, communication and patient safety, but led to reduced
      efficiency and longer duration of rounds.

PMID- 30228907
TI  - Risk of reoperation in bioprosthetic valve patients with indication for long-term
      anticoagulation. Results from the observational retrospective multicentre
      PLECTRUM study.
AB  - Objective: Several factors should be considered when a prosthetic heart valve,
      bioprosthetic valve (BV) or mechanical valve is to be implanted: thrombogenicity,
      life expectancy and the risk of reoperation. Methods: We conducted an
      observational retrospective multicentre study among Italian Thrombosis Centers on
      patients with BV on long-term vitamin K antagonist (VKA) treatment to evaluate
      the risk of reoperation and the rate of bleeding and thrombotic events. Results:
      We analysed 612 patients (median age 71.8 years) with BV on long-term VKA
      treatment for the presence of atrial fibrillation (AF) (78.4%) or other
      indications (21.6%). Thirty-four major bleeding events (rate 1.1*100 patient
      years) and 29 thromboembolic events (rate 0.9*100 patient-years) were recorded,
      and 46 patients (rate 1.5*100 patient-years) underwent reoperation. The rate of
      reoperation was higher among younger patients: 32.9% in patients <60 years and
      3.9% in patients >=60 years (relative risk (RR) 3.8, 95% CI 2.1 to 7.2;
      p=0.0001). When patients were analysed according to age <65 or >=65 years and <75
      or >=70 years, younger patients still were at higher risk for reoperation (RR
      3.1, 95% CI 1.7 to 6.0 and 3.7, 95% CI 1.7 to 8.6, respectively). Conclusions:
      Our findings suggest that the threshold of 65 years for implanting a BV should be
      carefully evaluated, considering the high risk for reoperation and the high risk
      of AF occurrence with persisting need for long-term anticoagulation. The high
      risk for reoperation of young patients implanted with BV and the availability of
      a safer and easier way to conduct VKA treatment, such as the use of point-of-care
      devices, should be considered when the type of valve must be chosen.

PMID- 30228908
TI  - Culprit vessel: impact on short-term and long-term prognosis in patients with ST
      elevation myocardial infarction.
AB  - Background: ST-elevation myocardial infarction (STEMI) occurs as a result of
      rupture of an atherosclerotic plaque in the coronary arteries. Limited data exist
      regarding the impact of culprit coronary vessel on hard clinical event rates.
      This study investigated the impact of culprit vessel on outcomes after primary
      percutaneous coronary intervention (PCI) of STEMI. Methods: A total of 29 832
      previously cardiac healthy patients who underwent primary PCI between 2003 and
      2014 were prospectively included from the Swedish Coronary Angiography and
      Angioplasty Registry and the Registry of Information and Knowledge about Swedish
      Heart Intensive care Admissions. Patients were stratified into three groups based
      on culprit vessel (right coronary artery (RCA), left anterior descending artery
      (LAD) and left circumflex artery (LCx)). The primary outcome was 1-year
      mortality. The secondary outcomes included 30-day and 5-year mortality, as well
      as heart failure, stroke, bleeding and myocardial reinfarction at 30 days, 1 year
      and 5 years. Univariable and multivariable analyses were done using Cox
      regression models. Results: One-year analyses revealed that LAD infarctions had
      the highest increased risk of death, heart failure and stroke compared with RCA
      infarctions, which had the lowest risk. Sensitivity analyses revealed that
      reduced left ventricular ejection fraction on discharge partially explained this
      increased relative risk in mortality. Furthermore, landmark analyses revealed
      that culprit vessel had no significant influence on 1-year mortality if a patient
      survived 30 days after myocardial infarction. Subgroup analyses revealed female
      sex and multivessel disease (MVD) as significant high-risk groups with respect to
      1-year mortality. Conclusions: LAD and LCx infarctions had a relatively higher
      adjusted mortality rate compared with RCA infarctions, with LAD infarctions in
      particular being associated with an increased risk of heart failure, stroke and
      death. Culprit vessel had limited influence on mortality after 1 month. High-risk
      patient groups include LAD infarctions in women or with concomitant MVD.

PMID- 30228909
TI  - Incidental abnormal CT scan findings during transcatheter aortic valve
      implantation assessment: incidence and implications.
AB  - Objectives: The aim of this retrospective series is to describe the prevalence
      and clinical significance of the incidental findings found during pre
      transcatheter aortic valve implantation (TAVI) work-up and to ascertain the
      clinical course of such patients. Methods: Consecutive patients undergoing TAVI
      from 2013 to 2015 where a TAVI CT assessment was performed (n=138) were included
      in the study. All incidental findings that were not expected from the patient's
      history were discussed at the TAVI multidisciplinary meeting in order to
      ascertain the clinical significance of said findings and whether they would alter
      the proposed course of treatment. Mortality data were determined by careful
      retrospective case note and follow-up appointment analysis. Results: Seventy
      eight patients (57%) were found to have incidental findings on pre-TAVI CT scan.
      The majority of patients had benign pathology with high incidence in particular
      of diverticular disease, pleural effusions, gallstones, hiatus hernia and
      degenerative spinal disease. Vascular pathology such as superior mesenteric,
      renal and iliac artery stenoses and abdominal aortic aneurysm was detected in
      seven patients. In terms of long-term mortality data, we found no significant
      difference between those with incidental findings and those without (p=0.48).
      Survival as assessed by Kaplan-Meier analysis showed no significant difference
      between those with and without incidental abnormal CT scan findings (p=0.98).
      Conclusions: Incidental findings with potential for malignancy are common in an
      elderly, comorbid population. Ultimately, clinical correlation and prognosis must
      be swiftly ascertained in order to streamline the patients down the appropriate
      management pathway while avoiding unnecessary delay for treatment of their aortic
      stenosis.

PMID- 30228910
TI  - Male-female differences in aortic valve and combined aortic valve/coronary
      surgery: a national cohort study in the Netherlands.
AB  - Objective: The outcome of female patients after adult cardiac surgery has been
      reported to be less favourable compared with the outcome of male patients. This
      study compares men with women with respect to patient and procedural
      characteristics and early mortality in a contemporary national cohort of patients
      who underwent aortic valve (AV) and combined aortic valve/coronary (CABG/AV)
      surgery. Methods: All patients who underwent AV (n=8717, 56% male) or a combined
      CABG/AV surgery (n=5867, 67% male) in the Netherlands between January 2007 and
      December 2011 were included. Results: In both groups, women were generally older
      than men (p<0.001) and presented with higher logistic EuroSCORES. In isolated AV
      surgery, men and women had comparable in-hospital mortality (OR 1.20, 95% CI 0.90
      to 1.61; p=0.220). In concomitant CABG/AV surgery, in-hospital mortality was
      higher in women compared with men (OR 2.00, 95% CI 1.44 to 2.79; p<0.001). The
      area under the curve for logistic EuroSCORE 1 was systematically higher for men
      versus women in isolated AV surgery 0.82 (95% CI 0.78 to 0.86) vs 0.75 (95% CI
      0.69 to 0.80) and in concomitant CABG/AV surgery 0.78 (95% CI 0.73 to 0.82) vs
      0.69 (95% CI 0.63 to 0.74). Finally, (the weight of) risk factors associated with
      in-hospital mortality differed between men and women. Conclusions: There are
      substantial male-female differences in patient presentation and procedural
      aspects in isolated AV and concomitant CABG/AV surgery in the Netherlands.
      Further studies are necessary to explore the mechanisms underlying the observed
      differences. In addition, the observation that standard risk scores perform worse
      in women warrants exploration of male-female specific risk models for patients
      undergoing cardiac surgery.Brief title.

PMID- 30228912
TI  - Correction: Risk factors for incident heart failure with preserved or reduced
      ejection fraction, and valvular heart failure, in a community-based cohort.
AB  - [This corrects the article DOI: 10.1136/openhrt-2018-000782.].

PMID- 30228911
TI  - Comparative early outcomes of tricuspid Valve repair versus replacement for
      secondary tricuspid regurgitation.
AB  - Background: Comparative outcome data on tricuspid valve repair (TVr) versus
      tricuspid valve replacement (TVR) for severe secondary tricuspid regurgitation
      (TR) are limited. Methods: We used a national inpatient sample to assess in
      hospital morbidity and mortality, length of stay and cost in patients with severe
      secondary TR undergoing isolated TVr versus TVR. Results: A total of 1364
      patients (national estimate=6757) underwent isolated tricuspid valve surgery
      during the study period, of whom 569 (41.7%) had TVr and 795 (58.3%) had TVR.
      There was no difference in the prevalence of major morbidities between the two
      groups, except for liver disease and hepatic cirrhosis, which were more common in
      the TVR group. Before propensity matching, in-hospital mortality was similar
      between patients who underwent isolated TVr and TVR (8.1% vs 10.8%, p=0.093), but
      the incidence of postoperative morbidities differed: TVR was associated with
      higher rates of permanent pacemaker implantation and blood transfusion, while TVr
      was associated with more acute kidney injury. After rigorous propensity score
      matching, TVR was associated with significantly higher rates of in-hospital death
      (12% vs 6.9%, p=0.009) and permanent pacemaker implantation (33.7% vs 11.2%,
      p<0.001). Postoperative morbidities and length of stay, however, were not
      different between the two groups. Nonetheless, cost of hospitalisation was 16%
      higher in the TVr group. Conclusions: In patients undergoing isolated surgery for
      secondary TR, TVR is associated with higher in-hospital mortality and need for
      permanent pacemaker compared with TVr. Further studies are needed to understand
      the impact of the type of surgery on the short-term and long-term mortality in
      this complex undertreated population.

PMID- 30228913
TI  - Evaluation of Sutureless, Glueless, Flapless, Intrascleral Fixated Posterior
      Chamber Intraocular Lens in Children with Ectopia Lentis.
AB  - Aim: This paper aims at evaluating refractive outcome and complication profile of
      sutureless, glueless, flapless, intrascleral fixation of intraocular lens (SFIOL)
      in pediatric population. Methods: This retrospective study included patients <=18
      years of age who underwent SFIOL for ectopia lentis. Details obtained included
      preoperative uncorrected visual acuity (UCVA), cycloplegic refraction, and best
      corrected visual acuity (BCVA); intraoperative complications; and postoperative
      UCVA, cycloplegic refraction, and BCVA and complications. Results: Median pre-
      and postoperative UCVA was logMAR 1.78 (Snellen 20/1200) and logMAR 0.30 (Snellen
      20/40), respectively, (p < 0.001). Median pre- and postoperative BCVA was logMAR
      0.24 (Snellen 20/34) and logMAR 0.18 (Snellen 20/30), respectively. UCVA >=20/60
      was attained in 90% of eyes. BCVA >=20/30 was attained in 85.0% of eyes. Most
      common early postoperative complications were hyphaema (10%), transient vitreous
      hemorrhage (2.5%), and ocular hypotony (2.5%). None of these developed any long
      term sequelae. Only one case of subluxation of IOL was seen. No case of late
      endophthalmitis or retinal detachment was seen. Conclusion: Since refractive
      error induced is minimal, the procedure is suitable for IOL implantation in
      children, who are noncompliant with spectacles. The complication profile is
      similar to that reported in adults.

PMID- 30228914
TI  - The Increment of Choroidal Thickness in Euthyroid Graves' Ophthalmopathy: Is It
      an Early Sign of Venous Congestion?
AB  - Objective: Clinical manifestations of Graves' ophthalmopathy (GO) are caused by
      the overcompression of orbital tissues within the restricted orbital bone cavity.
      Impaired ocular blood flow may disrupt the retinal microstructure and functions.
      In this study, we aimed to investigate the macular and choroidal thickness
      changes in GO compared with healthy subjects. Materials and Methods: The study
      group comprised 50 adult patients with previously diagnosed Graves' disease with
      ophthalmopathy who were on antithyroid treatment. For the assessment of GO
      activity, the VISA (vision, inflammation, strabismus, and appearance)
      inflammatory score was used. When euthyroidism was achieved without side effects,
      the patients were referred to the ophthalmology clinic for spectral-domain
      optical coherence tomography (SD-OCT) evaluation. Results: Subfoveal, mean, and
      temporal choroidal thicknesses were increased significantly in the study group
      according to the controls. The mean choroidal thickness was elevated.
      Conclusions: This elevation is because of the intraorbital inflammation even in
      this nonsevere GO group. Choroidal thickness might be affected from the venous
      obstruction and congestion in patients with GO. The elevation of the choroidal
      thickness might be an early sign of venous congestion that occurs before the
      elevation of intraocular pressure.

PMID- 30228915
TI  - Endocrown: An Alternative Approach for Restoring Endodontically Treated Molars
      with Large Coronal Destruction.
AB  - Rehabilitation of endodontically treated molar still remains a challenge. After
      endodontic treatment, molars lost their mechanical characteristics. In fact, they
      became fragile and that is in relation with the removal of pulp and surrounding
      dentin tissues. Endocrown which is a single partial restoration could be
      considered as a good alternative for restoring molars having large coronal
      destruction and presenting endodontic treatment difficulties. Through this work,
      we discuss the indication and use of endocrown to replace single crowns with
      intraradicular retention and to present a clinical case report of an endocrown
      type restoration, fabricated from lithium disilicate ceramic (IPS e.Max CAD) in a
      mandibular first molar with extensive coronal destruction.

PMID- 30228916
TI  - Lingual Leiomyomatous Hamartoma in an Adult Male.
AB  - An otherwise healthy 20-year-old male presented with an exophytic, polypoid,
      yellowish lesion involving the dorsal surface of his tongue, which he reported
      being present since birth and unchanged. This was removed by surgical excision
      and diagnosed as a leiomyomatous hamartoma. Histological examination revealed a
      combination of fibrovascular connective tissue, conspicuous smooth-muscle
      bundles, adipose tissue, minor salivary gland tissue, blood vessels, lymphoid
      tissue, peripheral nerves, and normal skeletal muscle. This case is exceptional
      due to the patient's age, as until now, lingual leiomyomatous hamartomas have
      been reported almost exclusively in a paediatric population. To our knowledge,
      this is the eldest age at which a LLH has been reported in the literature. This
      underscores the need for clinicians to consider this rarely reported entity when
      considering the radiographic and clinical differential diagnoses for these
      lesions, both in the paediatric and adult populations. We also present a review
      of the literature regarding lingual leiomyomatous hamartomas.

PMID- 30228917
TI  - Thromboelastometry Identified Alteration of Clot Stabilization and Factor XIII
      Supplementation Need in a Patient with Decompensated Liver Disease Undergoing
      Liver Biopsy.
AB  - Liver disease has been considered the prototype of hemorrhagic disease. Disorder
      in any component of coagulation system can lead to hemorrhage. Deficiency of
      factor XIII may impair clot strength and clot stabilization and can be accessed
      by thromboelastometry. We report a case of a patient with a rapid evolution of
      liver disease who underwent a liver biopsy. Thromboelastometry was performed,
      evidencing impairment of clot stability. This clotting disorder was corrected
      with factor XIII concentrate after unsuccessful administration of
      antifibrinolytic drugs and hepatic biopsy was performed without hemorrhagic
      complications. Case Presentation. We report the case of a previously healthy 38
      year-old man, who presented to our emergency department with clinical signs of
      rapid progression of acute liver failure. The laboratory tests revealed platelets
      of 142x103/mm3, plasma fibrinogen concentration of 221 mg/dl, increased
      international nationalized ratio (INR 1.9), total bilirubin of 3.9mg/dl, direct
      bilirubin of 2.3mg/dl, ALT 751U/l, and AST 540U/l without acute bleeding. A liver
      biopsy was indicated. Based on the results of the thromboelastometry, Tranexamic
      Acid was administered to correct hyperfibrinolysis followed by factor XIII
      concentrate to correct factor XIII deficiency. Thromboelastometry was normal
      despite conventional coagulation tests were still altered. So, liver biopsy was
      performed with no signs of bleeding and without need of further transfusion.
      Conclusion. Thromboelastometry may be considered a useful, feasible, and safe
      tool to monitor and manage coagulopathy in patients with liver disease, with the
      potential advantage of helping avoid unnecessary transfusion in such patients.

PMID- 30228918
TI  - A Case of Bing-Neel Syndrome Successfully Treated with Ibrutinib.
AB  - Bing-Neel syndrome is a rare manifestation of Waldenstrom macroglobulinemia
      characterized by lymphoplasmacytic cells' infiltration into the central nervous
      system. We present a case of a 74-year-old patient with a known diagnosis of
      Waldenstrom macroglobulinemia and newly depressed consciousness. Flow cytology of
      his cerebral spinal fluid demonstrated a lambda light chain-restricted population
      of B-cells consistent with a CD5+ CD10+ B-cell lymphoma. Magnetic resonance
      imaging suggested involvement of the left optic nerve sheath and the bilateral
      orbital and parietal parenchyma and leptomeninges. He was diagnosed with Bing
      Neel syndrome and treated with intrathecal liposomal cytarabine, intravenous high
      dose methotrexate, and rituximab without improvement. Subsequently, he started
      treatment with ibrutinib 560 mg daily and concurrent rituximab. Within three
      months, he showed clinical and radiologic improvement. The patient has continued
      on ibrutinib and has now been stable for over 36 months. This represents the
      longest reported period of successful treatment of Bing-Neel syndrome with
      ibrutinib.

PMID- 30228919
TI  - Femur Fracture Associated with Knee Brace Wear in the Motocross Athlete: A Report
      of Two Cases and Review of the Literature.
AB  - The sport of motocross entails off-road motorcycle racing and is associated with
      a high incidence of traumatic injury. While prophylactic knee braces are
      routinely worn, there has been anecdotal concern that brace use is linked to
      femoral shaft fractures. While this risk remains unreported in the medical
      literature, preventing this complication has played a role in new commercial knee
      brace designs. We present two cases in which two motocross riders sustained
      transverse femoral shaft fractures at the proximal portion of each respective
      knee brace. The fracture locations measured on anterior-posterior radiograph were
      22 and 21.1 cm proximal to the center of the knee, which is also the recommended
      proximal extent of motocross knee braces. We propose that the rigid knee brace
      protects the ligamentous knee structures but may focus undue force on the
      proximal aspect of the brace. New knee brace designs have incorporated features
      to dissipate the potentially injurious force to prevent femur fracture. While
      knee braces undoubtedly help prevent ligamentous knee injury, these cases
      question the safety of standard brace design and highlight the need for further
      brace development to better protect the patient's bony structures, in addition to
      the knee joint.

PMID- 30228920
TI  - Calcaneus Metastasis from Follicular Thyroid Carcinoma 12 Years after Total
      Thyroidectomy.
AB  - We report the case of a sixty-eight-year-old female patient who presented for
      left ankle pain; X-rays and MRI showed a benign calcaneal cyst, found to be
      delayed distant metastasis from primary papillary thyroid carcinoma. Patient
      required surgical excision of the cyst. Results of histological examination
      showed metastatic papillary thyroid carcinoma. The patient underwent total
      thyroidectomy 12 years prior to presentation, with the same pathology.
      Postoperatively, she was treated with radioactive iodine. At 10-year follow-up
      post calcaneal mass excision, she was found to have a right proximal tibial mass
      and found to be recurrent with the same pathology. This case reports a rare
      condition that will be taken into consideration in bone metastasis with thyroid
      cancer.

PMID- 30228922
TI  - Early Gastric Cancer with Purely Enteroblastic Differentiation and No
      Conventional Adenocarcinoma Component.
AB  - Gastric carcinoma with enteroblastic differentiation (GCED) is a rare variant of
      gastric carcinoma, and a part of GCED produces alpha-fetoprotein. GCED is
      characterized by cells with clear cytoplasm and a tubulopapillary and solid
      growth pattern resembling those in the primitive gut. GCED is typically overlaid
      by a conventional adenocarcinoma (CA) component, implying that CA in the mucosa
      differentiates into GCED during tumor invasion and proliferation. We present the
      case of a 73-year-old woman with a 10-mm superficial elevated lesion and a slight
      central depression at the anterior wall of the lower gastric body. Endoscopic
      submucosal dissection revealed tumor cells having clear cytoplasm and severely
      atypical nuclei characteristic of GCED. The growth pattern was predominantly
      solid and trabecular but included submucosal layer invasion and limited tubular
      growth. Atrophic pyloric mucosa without intestinal metaplasia surrounded the
      tumor. Immunohistochemically, the tumor cells were positive for AFP, GPC3, and
      SALL4. The present patient showed a purely enteroblastic differentiation without
      a CA component despite the presence of early cancer, indicating that few cases of
      GCED may arise de novo in the gastric mucosa. GCED is more aggressive compared
      with CA; therefore, pathologists should be aware that GCED without CA can appear
      in biopsy specimens of early cancer while making an accurate diagnosis.

PMID- 30228921
TI  - A Composite Renal Tumor with Dual Differentiation, Chromophobe and Collecting
      Duct Carcinoma.
AB  - Chromophobe carcinoma constitutes a small subset of all renal carcinomas. Within
      this category, rare tumors with divergent differentiation have been recognized.
      Herein, we report a rare case of composite chromophobe and collecting duct
      carcinoma and describe its pathologic and clinical features.

PMID- 30228923
TI  - Pediatric Pancreatic Tuberculosis: A Case Report and Review of the Literature.
AB  - Pancreatic tuberculosis (TB) is an uncommon form of extrapulmonary TB and
      represents a diagnostic challenge for physicians. Pancreatic TB presents with
      nonspecific signs and symptoms and may mimic malignancy. However, pancreatic TB
      rarely occurs in children. Here, we present a case of a 5-year-old girl with
      pancreatic TB and markedly elevated serum cancer antigen- (CA-) 125 levels, thus
      raising the suspicion of malignancy, but positivity for Mycobacterium
      tuberculosis DNA was noted. The patient recovered after being administered
      standard antitubercular therapy for one year. This case suggests that clinicians
      should have a heightened suspicion of pancreatic TB when faced with pancreatic
      lesions despite the fact that increased CA-125 may indicate malignancy.
      Laparoscopy combined with peritoneal biopsy and polymerase chain reaction (PCR)
      may provide a new method to confirm the diagnosis.

PMID- 30228924
TI  - Multiple Giant Coronary Artery Aneurysms Surgically Treated with Bypass Grafting:
      A Challenging Rarity.
AB  - Coronary artery aneurysms are encountered in daily cardiology practise but
      multiple giant-sized coronary artery aneurysms are extremely rare. We present an
      illustrative case of multiple giant aneurysms located throughout the coronary
      system (left main stem and all left, right, and circumflex branches) in a 57-year
      old male with acute coronary syndrome. The case was managed successfully with on
      pump quadruple coronary artery bypass grafting. To our knowledge, few cases of
      multiple giant aneurysms in all coronary vessels have been reported.

PMID- 30228925
TI  - Prostatic Abscess on Xanthogranulomatous Prostatitis: Uncommon Complication of an
      Uncommon Disease.
AB  - Xanthogranulomatous prostatitis is a rare benign inflammatory process of the
      prostate. Only few cases have been reported in the English literature.
      Xanthogranulomatous prostatitis is usually an incidental finding after needle
      biopsy or transurethral resection of the prostate in patients suffering from low
      urinary tract symptoms. We report the case of a 59-years-old patient diagnosed
      with prostatic abscess managed by transurethral resection of the prostate.
      Histopathological examination of resected prostatic tissue revealed abscessed
      xanthogranulomatous prostatitis with no evidence of malignancy.
      Xanthogranulomatous prostatitis presenting as a prostatic abscess is a rare
      finding. To the best of our knowledge our case represents the fourth case of
      xanthogranulomatous prostatitis presenting as prostatic abscess reported in the
      English literature so far.

PMID- 30228927
TI  - Development and Validation of a High-Performance Liquid Chromatographic Method
      for the Determination of Cinitapride in Human Plasma.
AB  - A precise and reliable reversed-phase high-performance liquid chromatographic
      method with ultraviolet detection was developed and validated to determine
      cinitapride in human plasma. After liquid-liquid extraction, chromatographic
      separation was achieved on a Nucleosil C18 (25 cm * 4.6 mm, 5 um) column with an
      isocratic elution consisting of 10 mM ammonium acetate (pH 5.2), methanol, and
      acetonitrile, 40 : 50 : 10, v/v/v. The developed method was validated as per US
      FDA guidelines for its linearity, selectivity, sensitivity, precision, accuracy,
      and stability. Satisfactory findings were obtained from the validation studies.
      The linearity range of the method was 1 to 35 ng/mL while the extraction recovery
      of cinitapride in human plasma was more than 86%. The percent coefficient of
      variation of both intraday and interday precision was <=7.1%.

PMID- 30228926
TI  - New Advances in Toxicological Forensic Analysis Using Mass Spectrometry
      Techniques.
AB  - This article reviews mass spectrometry methods in forensic toxicology for the
      identification and quantification of drugs of abuse in biological fluids,
      tissues, and synthetic samples, focusing on the methodologies most commonly used;
      it also discusses new methodologies in screening and target forensic analyses, as
      well as the evolution of instrumentation in mass spectrometry.

PMID- 30228928
TI  - A Descriptive Review of the Prevalence and Usage of Traditional and Complementary
      Medicine among Saudi Diabetic Patients.
AB  - Diabetes mellitus represents a major burden in Saudi Arabia where seven million
      (20% of population) are living with diabetes. This article reviews the literature
      on usage of traditional and complementary medicine (T&CM) therapies among Saudi
      diabetic patients, focusing in particular on identifying the prevalence as well
      as discussing their safety and efficacy. Three databases (PubMed, Cochrane, and
      ScienceDirect) were searched prior to December 10, 2017, for articles published
      in peer-reviewed journals that reported primary data on the use of traditional
      and complementary medicine therapies among diabetic patients in Saudi Arabia. Six
      studies were selected according to the inclusion/exclusion criteria. In
      conclusion, the prevalence of use of T&CM therapies among diabetics in Saudi
      Arabia was 32.18%. This review identified that the most used T&CM therapy among
      diabetics was herbal treatment. The most used herbs were fenugreek, black seeds,
      neem, myrrh, helteet, harmel, and aloes. There is insufficient or little evidence
      to support the efficacy of the most identified herbs and therapies. This review
      is raising the safety concerns about the used herbs and complementary therapies
      which were commonly used without any medical consultation.

PMID- 30228929
TI  - Rhinolithiasis: A Misleading Entity.
AB  - Introduction: Rhinolithiasis is a rare entity; it entails a stone located in the
      nasal cavity. The entity presents with different signs and symptoms that can be
      easily confused with other more common clinical entities such as chronic
      rhinosinusitis. However, it can also mimic sinonasal tumors, making its proper
      diagnosis crucial. Materials and Methods: In this article, we present a case
      series of 15 patients over the past 13 years between 2002 and 2015 who were seen
      in the clinics at the American University of Beirut Medical Center. We will shed
      light on the common presenting symptoms, physical examination findings, proper
      diagnostic modalities, and treatment options. Our data will be compared to the
      literature. Conclusion: Rhinolithiasis could present with a wide spectrum of
      signs and symptoms and could be overlooked or mistaken for other diagnosis such
      as sinusitis or malignancy. It could be differentiated from other entities by
      rigid nasal endoscopy and computed tomography scan. The diagnosis of
      rhinolithiasis requires a high index of suspicion.

PMID- 30228930
TI  - Spillage of bacterial products during colon surgery increases the risk of liver
      metastases development in a rat colon carcinoma model.
AB  - Surgical resection of the primary tumor provides the best chance of cure for
      patients with colorectal carcinoma (CRC). However, bacterial translocation during
      intestinal surgery has been correlated with poor long-term oncological outcome.
      Therefore, we investigated the influence of bacterial contamination during colon
      surgery on CRC liver metastases development. Blood and liver samples of patients
      undergoing resection of primary CRC or liver metastases were collected. Cell
      numbers, activation markers and inflammatory mediators were determined. Tumor
      cell adhesion and outgrowth after sham- or colectomy operations were determined
      in a rat model, in which tumor cells had been injected into the portal vein.
      White blood cells and granulocytes were increased in per- and post-operative
      patient blood samples. IL-6 was also increased post-operatively compared to the
      preoperative level. Expression of NOX-2, NOX-4 and polymorphonuclear cells (PMNs)
      numbers were elevated in post-operative human liver samples. In vitro stimulation
      of macrophages with plasma of rats after colectomy resulted in production of
      reactive oxygen species (ROS). Colectomy in rats increased D-lactate levels in
      plasma, supporting bacterial translocation. Decreased expression of tight
      junction molecules and increased tumor cell adhesion and outgrowth was observed.
      Treatment with a selective decontamination of the digestive tract (SDD) cocktail
      decreased tumor cell adherence after colectomy. In conclusion, postoperative
      bacterial translocation may activate liver macrophages and PMNs, resulting in ROS
      production. As we previously showed that ROS release led to liver vasculature
      damage, circulating tumor cells may adhere to exposed extracellular matrix and
      grow out into liver metastases. This knowledge is pivotal for development of
      therapeutic strategies to prevent surgery-induced liver metastases development.

PMID- 30228931
TI  - Subgroup-specific immune and stromal microenvironment in medulloblastoma.
AB  - Knowledge on immune and stromal cells in medulloblastoma microenvironment is
      still limited as previous work was frequently restricted by low sample size and
      the lack of molecular subgroup information. We characterized 10 microenvironment
      cell populations as well as PD-L1 from gene expression in 1422 brain tumors and
      763 medulloblastomas. All in all, medulloblastomas showed low expression of
      immune markers. Still, there were substantial differences with a clustering of
      medulloblastoma subgroups according to their microenvironment profile.
      Specifically, SHH medulloblastomas displayed strong signatures of fibroblasts, T
      cells and macrophages, while markers of cytotoxic lymphocytes were enriched in
      Group 4 tumors. PD-L1 gene expression appeared to be relatively high in single
      SHH and WNT cases but was undetectable by immunohistochemistry. In addition, two
      diverse immuno-stromal patterns were identified, indicating distinct types of
      local tumor immunosuppression, which were primarily controlled by either
      macrophage and regulatory T cell-mediated mechanisms or immunosuppressive
      cytokines and checkpoints, respectively. None of the immune cell signatures had
      an independent prognostic value in the present dataset after multiple testing
      correction. These results suggest a mild, but subgroup-specific infiltration of
      immune cells in medulloblastoma.

PMID- 30228932
TI  - TumGrowth: An open-access web tool for the statistical analysis of tumor growth
      curves.
AB  - The analysis of tumor growth curves is standard practice in experimental oncology
      including tumor immunology. In experimental oncology, cancer cells are inoculated
      into rodents (mostly mice) and their growth is monitored by measuring tumor
      diameter, surface or volume over time as a function of distinct treatments. Then,
      different groups of tumors/treatments are compared among each other for their
      evolution and possible responses to treatment. The R package TumGrowth has been
      created as a software tool allowing to carry out a series of statistical
      comparisons across or between groups of tumor growth curves obtained in a
      standard laboratory, for experimenters with limited knowledge in statistics.
      TumGrowth is freely available online at
      https://kroemerlab.shinyapps.io/TumGrowth/ and can be downloaded into any
      computer. It offers an exhaustive panoply of tools to visualize and analyze
      complex data sets including longitudinal, cross-sectional and time-to-endpoint
      measurements.

PMID- 30228933
TI  - Dynamic evaluation of the immune infiltrate and immune function genes as
      predictive markers for neoadjuvant chemotherapy in hormone receptor positive,
      HER2 negative breast cancer.
AB  - Gene expression (GE) signatures and Tumor Infiltrating Lymphocytes (TIL)
      enumeration are predictive for response to neoadjuvant chemotherapy in HR- and in
      HER2+ breast cancer, but data are conflicting in HR+/HER2- disease. This study
      aimed to explore their predictive value in this subset, measured both at baseline
      and after short exposure to chemotherapy. Specifically, the PROMIX phase 2 trial
      enrolled patients with locally advanced HER2- BC to receive six cycles of
      epirubicin and docetaxel, plus bevacizumab during cycles 3-6. Patients underwent
      tumor biopsies at baseline and after cycle 2 for GE profiling and enumeration of
      TIL, FOXP3+ T-cells and CD163+ macrophages. An immune related gene module and the
      quantification of the immune infiltrate were analyzed for association with
      pathologic complete response (pCR), decrease in tumor size and disease-free
      survival (DFS). Of the 150 patients enrolled in PROMIX, 113 were HR+/HER2-.
      Baseline GE and immune cell enumeration data were available from 71 patients,
      while data after 2 cycles of chemotherapy were available from 41. At baseline,
      only GE was statistically significantly associated with higher pCR rates (OR
      2.29, 95% CI 1.05 - 5.38, p = 0.037) and decrease in tumor size (r = 0.25, p =
      0.047). In contrast, longitudinal data indicate that both GE (r = 0.54, p<0.001)
      and TIL abundance (p = 0.009) are stronger predictors for the reduction of tumor
      size, while low FOXP3+ was statistically significantly associated with an
      improved DFS (p = 0.027). In conclusion, GE analysis, TIL and FOXP3+ enumeration
      after short-term exposure to chemotherapy carry important predictive information
      in HR+/HER2- breast cancer at the neoadjuvant setting.

PMID- 30228934
TI  - Losses of cytokines and chemokines are common genetic features of human cancers:
      the somatic copy number alterations are correlated with patient prognoses and
      therapeutic resistance.
AB  - Intricate relationships among cytokines (including chemokines) shape the tumor
      microenvironment (TME) and reflect cell-cell interactions between malignant cells
      and other cells from the TME. Although our previous study indicated the
      transcriptional landscape of cytokines in 19 cancer types, the global pattern
      somatic copy number (SCN) alterations and the clinical relevance of cytokines
      have not been systematically investigated. Here, we reported a significant
      negative selection on cytokine genes. We also linked the SCN losses of cytokine
      genes to the abundance of immune infiltrates which affects cancer progression and
      patient prognoses. We also demonstrated and validated the correlations between
      SCN alterations of cytokine-containing loci and drug sensitivity. The results
      indicated the genomic loss of cytokines in malignant cells as a crucial theme for
      interrogating cancer progression, malignant cell-TME interactions, and
      therapeutics.

PMID- 30228935
TI  - Immunological effects of BRAF+MEK inhibition.
AB  - Recent developments in immunotherapy have prolonged overall survival in
      metastatic melanoma with the possibility to reach a long-term benefit. Targeted
      therapies based on BRAF and MEK inhibition also seem to have a long-term
      beneficial effect, which is more evident in patients with favorable baseline
      characteristics, namely normal levels of lactate dehydrogenase, without brain
      metastases, and low tumor burden. This long-term benefit of targeted therapies
      might be related to an immune-modulation: indeed BRAF and MEK inhibitors affect
      tumor microenvironment and immune surveillance, and it has been shown that
      patients with complete response to targeted treatment have a pre-existing
      favorable immunologic signature.

PMID- 30228936
TI  - Spontaneous T-cell responses against Arginase-1 in the chronic myeloproliferative
      neoplasms relative to disease stage and type of driver mutation.
AB  - Compelling evidence supports the existence of a profound immune dysregulation in
      patients with chronic myeloproliferative neoplasms (MPN). Increased Arginase-1
      expression has been described in MPN patients and in solid cancers. This increase
      contributes to an immunosuppressive tumor microenvironment in MPN patients
      because of L-arginine depletion by Arginase-1-expressing regulatory cells and
      cancer cells, which subsequently limits the activation of circulating effector
      cells. In the present study, we demonstrate that Arginase-1-derived peptides are
      recognized by T cells among peripheral mononuclear blood cells from MPN patients.
      We characterized the Arginase-1-specific T cells as being CD4+ and found that the
      magnitude of response to the Arginase-1 peptides depends on disease stage.
      Activation of Arginase-1-specific T cells by vaccination could be an attractive
      novel immunotherapeutic approach to targeting malignant and suppressive cells in
      MPN patients in combination with other immunotherapeutics.

PMID- 30228937
TI  - VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response
      in patients with AML.
AB  - Treatment of acute myeloid leukemia (AML) remains challenging. Enhancement of
      anti-tumor responses by blocking negative immune regulators is a promising
      strategy for novel effective leukemia therapeutics. V-domain Ig suppressor of T
      cell activation (VISTA) is a recently defined negative regulator mediating immune
      evasion in cancer. To investigate the effect of VISTA on anti-leukemia immune
      response in AML, we initiated a study using clinical samples collected from AML
      patients. Here we report that VISTA is highly expressed on myeloid-derived
      suppressor cells (MDSCs) in the peripheral blood of AML patients. Both the
      frequency and intensity of VISTA expression on MDSCs are significantly higher in
      newly diagnosed AML than in healthy controls. Importantly knockdown of VISTA by
      specific siRNA potently reduced the MDSCs-mediated inhibition of CD8 T cell
      activity in AML, suggesting a suppressive effect of VISTA on anti-leukemia T cell
      response. Furthermore, we observed a strong positive association between MDSC
      expression of VISTA and T cell expression of PD-1 in AML. These results support
      the strategy of VISTA-targeted treatment for AML and underscore the strong
      potential for combined blockade of VISTA and PD-1 pathways in effective leukemia
      control.

PMID- 30228938
TI  - Recruitment of CCR2+ tumor associated macrophage to sites of liver metastasis
      confers a poor prognosis in human colorectal cancer.
AB  - The tumor microenvironment (TME) represents a significant barrier to creating
      effective therapies for metastatic colorectal cancer (mCRC). In several
      malignancies, bone marrow derived CCR2+ inflammatory monocytes (IM) are recruited
      to the TME by neoplastic cells, where they become immunosuppressive tumor
      associated macrophages (TAM). Here we report that mCRC expression of the
      chemokine CCL2 facilitates recruitment of CCR2+ IM from the bone marrow to the
      peripheral blood. Immune monitoring of circulating monocytes in patients with
      mCRC found this influx was a prognostic biomarker and correlated with worse
      clinical outcomes. At the metastatic site, mCRC liver tumors were heavily
      infiltrated by TAM, which displayed a robust ability to dampen endogenous anti
      tumor lymphocyte activity. Using a murine model of mCRC that recapitulates these
      findings from human disease, we show that targeting CCR2 reduces TAM accumulation
      in liver metastasis and restores anti-tumor immunity. Additional quantitative
      analysis of hepatic metastatic tumor burden and treatment efficacy found that
      administration of a small molecule CCR2 inhibitor (CCR2i) improves
      chemotherapeutic responses and increases overall survival in mice with mCRC liver
      tumors. Our study suggests that targeting the CCL2/CCR2 chemokine axis decreases
      TAM at the metastatic site, disrupting the immunosuppressive TME and rendering
      mCRC susceptible to anti-tumor T-cell responses.

PMID- 30228940
TI  - Duokines: a novel class of dual-acting co-stimulatory molecules acting in cis or
      trans.
AB  - Co-stimulatory signals induced by ligands of the tumor necrosis factor
      superfamily (TNFSF) play a central role in T cell activation and have emerged as
      a promising strategy in cancer immunotherapy. Here, we established a novel class
      of bifunctional co-stimulatory fusion proteins with the aim to boost T cell
      activation at the level of T cell - antigen-presenting cell (APC) interaction.
      These novel dual-acting cytokine fusion proteins were created by connecting two
      different homotrimeric TNFSF ligands to form homotrimeric bifunctional molecules
      (Duokines) or by connecting single-chain derivatives of two different
      homotrimeric TNFSF with a single, flexible linker (single-chain Duokines,
      scDuokines). By linking the TNFSF ligands 4-1BBL, OX40L and CD27L in all possible
      combinations, cis-acting Duokines were generated that act on the same or adjacent
      T cells, while combining CD40L with 4-1BBL, OX40L and CD27L resulted in trans
      acting Duokines acting simultaneously on APCs and T cells. In vitro, co
      stimulation of T cells was seen for cis- and trans-acting Duokines and scDuokines
      in an antigen-independent as well as antigen-specific setting. Trans-acting
      molecules furthermore activated B cells, which represent a subclass of APCs. In a
      pilot experiment using the syngeneic B16-FAP mouse tumor model scDuokines
      displayed antitumoral activity in vivo in combination with a primary T cell
      activating bispecific antibody, evident from reduced number of lung metastasis
      compared to the antibody-only treated group. Our data show that the bifunctional,
      co-stimulatory duokines are capable to enhance T cell-mediated anti-tumor immune
      responses, suggesting that they can serve as a new class of immuno-stimulatory
      molecules for use in cancer immunotherapy strategies.

PMID- 30228939
TI  - Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor.
AB  - The release of soluble ligands of activating Natural Killer (NK) cell receptors
      may represent a regulatory mechanism of NK cell function both in physiologic and
      in pathologic conditions. Here, we identified the extracellular matrix protein
      Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed
      by activated NK cells. When released as soluble molecule, NID1 regulates NK cell
      function by modulating NKp44-induced IFN-gamma production or cytotoxicity. In
      particular, it also modulates IFN-gamma production induced by Platelet-Derived
      Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be
      present at the cell surface. In this form or when bound to a solid support
      (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However,
      analysis by mass spectrometry revealed that exposure to bNID1 can induce in human
      NK cells relevant changes in the proteomic profiles suggesting an effect on
      different biological processes.

PMID- 30228941
TI  - Dual-targeting triplebody 33-16-123 (SPM-2) mediates effective redirected lysis
      of primary blasts from patients with a broad range of AML subtypes in combination
      with natural killer cells.
AB  - A number of agents designed for immunotherapy of Acute Myeloid Leukemia (AML) are
      in preclinical and early clinical development. Most of them target a single
      antigen on the surface of AML cells. Here we describe the development and key
      biological properties of a tri-specific agent, the dual-targeting triplebody SPM
      2, with binding sites for target antigens CD33 and CD123, and for CD16 to engage
      NK cells as cytolytic effectors. Primary blasts of nearly all AML patients carry
      at least one of these target antigens and the pair is particularly promising for
      the elimination of blasts and leukemia stem cells (LSCs) from a majority of AML
      patients by dual-targeting agents. The cytolytic activity of NK cells mediated by
      SPM-2 was analyzed in vitro for primary leukemic cells from 29 patients with a
      broad range of AML-subtypes. Blasts from all 29 patients, including patients with
      genomic alterations associated with an unfavorable genetic subtype, were lysed at
      nanomolar concentrations of SPM-2. Maximum susceptibility was observed for cells
      with a combined density of CD33 and CD123 above 10,000 copies/cell. Cell
      populations enriched for AML-LSCs (CD34pos and CD34pos CD38neg cells) from 2 AML
      patients carried an increased combined antigen density and were lysed at
      correspondingly lower concentrations of SPM-2 than unsorted blasts. These initial
      findings raise the expectation that SPM-2 may also be capable of eliminating AML
      LSCs and thus of prolonging survival. In the future, patients with a broad range
      of AML subtypes may benefit from treatment with SPM-2.

PMID- 30228942
TI  - Fluorouracil and bevacizumab plus anakinra for patients with metastatic
      colorectal cancer refractory to standard therapies (IRAFU): a single-arm phase 2
      study.
AB  - In preclinical models, IL-1beta inhibition could enhance the efficacy of
      fluorouracil (5-FU). In this phase 2 study, we assessed the activity and safety
      of 5-FU plus bevacizumab and anakinra (an IL-1beta and alpha inhibitor) in
      patients with metastatic colorectal (mCRC) refractory to chemotherapy and anti
      angiogenic therapy. Eligible patients had unresectable mCRC; were refractory or
      intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and
      anti-EGFR therapy (for tumors with wild-type KRAS). Patients were treated with a
      simplified acid folinic plus 5-FU regimen and bevacizumab (5 mg/kg) both
      administered by intravenous infusion for 30 min every 2 weeks. Anakinra (100 mg)
      was injected subcutaneously once daily. The primary endpoint was the 2-month
      response rate determined upon CHOI criteria. Thirty two patients with metastatic
      colorectal cancer were enrolled. Five patients demonstrated response (Choi
      criteria) and 22 patients had stable disease as the best 2-month overall
      response. Median progression-free and overall survival were 5.4 (95% CI, 3.6-6.6)
      and 14.5 months (95% CI, 9-20.6) respectively. Twenty patients experienced grade
      3 toxicity. No grade 4 or 5 toxicity related to therapy occurred. The most common
      grade 3 adverse events were neutropenia in 8 (25%) patients, digestive side
      effects in 7 (21.9%) patients and hypertension in 6 (18.75%) patients. No
      treatment-related deaths or serious adverse events were reported.5-FU plus
      bevacizumab and anakinra has promising activity and a manageable safety profile,
      suggesting that this combination might become a potential treatment option for
      patients with refractory mCRC.

PMID- 30228943
TI  - High expression of PD-1 and PD-L1 in ocular adnexal sebaceous carcinoma.
AB  - Ocular adnexal sebaceous carcinoma (OASC) is an aggressive malignancy that
      frequently recurs locally and metastasizes. Surgical extirpation may produce
      significant aesthetic morbidity, and effective systemic therapies for locally
      advanced or metastatic disease are largely ineffective. Immune checkpoint
      inhibitors have shown efficacy in the management of several solid tumors where
      tumor cell PD-L1 expression correlates with improved response. To determine
      whether OASC might be amenable to immune checkpoint blockade, we performed
      comprehensive immune profiling for CD3, CD8, PD-1, FOXP3, and PD-L1 in 24
      patients with primary OASC. The composition, distribution and density of the
      tumor associated immune infiltrate were quantified by automated image analysis
      and correlated with measures of clinical outcome. Tumor cells in 12 OASCs (50%)
      expressed PD-L1. Higher densities of CD3+ (p = 0.01), CD8+ (p = 0.006), and PD-1+
      (p = 0.024) tumor-associated T cells were associated with higher T category
      (>=T3a per the 7th edition of the American Joint Committee on Cancer staging
      manual). Higher tumor cell expression of PD-L1 correlated with higher density of
      PD-1+ tumor-associated T cells (p = 0.021). Since a CD3+ CD8+ PD-1 + T-cell
      infiltrate represents a "suppressed T-cell phenotype" apparently permissive
      toward OASC progression, our findings provide a mechanistic rationale for the
      effective application of immune checkpoint blockade in OASC to abrogate PD-1/PD
      L1 interaction and effectively unleash the immune infiltrate to treat higher
      stage tumors.

PMID- 30228944
TI  - Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer.
AB  - Advanced bladder cancer patients have limited therapeutic options resulting in a
      median overall survival (OS) between 12 and 15 months. Adoptive cell therapy
      (ACT) using tumor infiltrating lymphocytes (TIL) has been used successfully in
      treating patients with metastatic melanoma, resulting in a median OS of 52
      months. In this study, we investigated the feasibility of expanding TIL from the
      tumors of bladder cancer patients. Primary bladder tumors and lymph node (LN)
      metastases were collected. Tumor specimens were minced into fragments, placed in
      individual wells of a 24-well plate, and propagated in high dose IL-2 for four
      weeks. Expanded TIL were phenotyped by flow cytometry and anti-tumor reactivity
      was assessed after co-culture with autologous tumor digest and IFN-gamma ELISA.
      Of the 28 transitional cell bladder or LN tumors collected, 14/20 (70%) primary
      tumors and all of the LN metastases demonstrated TIL expansion. Expanded TIL were
      predominantly CD3+ (median 63%, range 10-87%) with a median of 30% CD8 + T cells
      (range 5-70%). TIL secreted IFN-gamma in response to autologous tumor. Addition
      of agonisitic 4-1BB antibody improved TIL expansion from primary bladder tumors
      regardless of pre-treatment with chemotherapy. This study establishes the
      practical first step towards an autologous TIL therapy process for therapeutic
      testing in patients with bladder cancer.

PMID- 30228945
TI  - Vitamin D deficiency in head and neck cancer patients - prevalence, prognostic
      value and impact on immune function.
AB  - Vitamin D deficiency is frequently observed in human cancer patients and a
      prognostic relevance could be shown for some entities. Additionally, it is known
      that vitamin D can stimulate the patients' antitumor immunity. However, valid
      epidemiological data for head and neck squamous cell carcinoma (HNSCC) patients
      are sparse and functional studies on a possible connection between vitamin D and
      the patients' immune system are missing. 25-OH vitamin D serum levels were
      analyzed in 231 HNSCC patients and 232 healthy controls and correlated with
      clinical data and patient survival. Intra- and peritumoral infiltration with T
      cell, NK-cell and macrophage populations was analyzed in 102 HNSCC patients by
      immunohistochemistry. In 11 HNSCC patients, NK-cells were isolated before and
      after vitamin D substitution and analyzed for their cytotoxic activity directed
      against a HNSCC cell line. Vitamin D serum levels were significantly lower in
      HNSCC patients compared with healthy controls. Low vitamin D levels were
      associated with lymphatic metastasis and a negative HPV status and were a
      significant predictor of poor overall survival. HNSCC patients with severe
      vitamin D deficiency showed significantly altered intra- and peritumoral immune
      cell infiltrate levels. After vitamin D substitution, the patients' NK cells
      showed a significant rise in cytotoxic activity. Taken together, we could show
      that Vitamin D deficiency is highly prevalent in HNSCC patients and is a
      predictor of poor survival. Vitamin D substitution used as an adjuvant in immune
      therapies such as cetuximab and nivolumab treatment could support antitumorigenic
      immune responses, thus contributing to the improvement of the patients' prognosis
      in the context of a multimodal therapy.

PMID- 30228946
TI  - Combination of radiation and interleukin 12 eradicates large orthotopic
      hepatocellular carcinoma through immunomodulation of tumor microenvironment.
AB  - Immunotherapies have shown promising results in certain cancer patients. For
      hepatocellular carcinoma (HCC), the multiplicity of an immunotolerant
      microenvironment within both the tumor, and the liver per se may limit the
      efficacy of cancer immunotherapies. Since radiation induces immunogenic cell
      death and inflammatory reactions within the tumor microenvironment, we
      hypothesized that a combination therapy of radiation and lasting local
      immunostimulating agents, achieved by intratumoral injection of an adenoviral
      vector encoding interleukin 12, may reverse the immunotolerant microenvironment
      within a well-established orthotopic HCC toward a state favorable for inducing
      antitumor immunities. Our data showed that radiation and IL-12 combination
      therapy (RT/IL-12) led to dramatic tumor regression in animals bearing large
      subcutaneous or orthotopic HCC, induced systemic effect against distant tumor,
      and significantly prolonged survival. Radiation monotherapy induced tumor
      regression at early times but afterwards most tumors regained exponential growth,
      while IL-12 monotherapy only delayed tumor growth. Mechanistic studies revealed
      that RT/IL-12 increased expression of MHC class II and co-stimulatory molecules
      CD40 and CD86 on tumor-infiltrating dendritic cells, suggesting an improvement of
      their antigen presentation activity. RT/IL-12 also significantly reduced
      accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and
      impaired their suppressive functions by reducing production of reactive oxygen
      species. Accordingly, tumor-infiltrating CD8+ T cells and NK cells were
      significantly activated toward the antitumor phenotype, as revealed by increased
      expression of CD107a and TNF-alpha. Together, our data showed that RT/IL-12
      treatment could reset the intratumoral immunotolerant state and stimulate
      activation of antitumor cellular immunity that is capable of eliminating large
      established HCC tumors.

PMID- 30228948
TI  - A practical guide to the handling and administration of personalized
      transcriptionally attenuated oncolytic adenoviruses (PTAVs).
AB  - The aim of this review is to provide practical information on the handling,
      storage, and administration procedures for personalized oncolytic adenoviruses
      (PTAVs), which have recently entered clinical trials. As described herein,
      personalized oncolytic viruses refer to transcriptionally attenuated (TA) type 5
      adenoviruses that are engineered to carry one or more neoantigenic transgenes
      derived from patient tumors. Vials of personalized viruses should be stored at 
      60 degrees C without refreezing after thawing to maintain infectivity. To prevent
      accidental exposure and transmission, full implementation of universal
      precautions for preparation, administration, and handling is required.
      Contaminated materials that come into contact with personalized viruses should be
      properly disposed of in accordance with local institutional procedures. Severely
      immunocompromised or pregnant healthcare workers should not prepare or administer
      personalized viruses or directly contact injection sites. Personalized viruses
      are administered subcutaneously and intratumorally; however, only subcutaneous
      injection will be considered in this review. The specific storage, handling,
      administration, and safety requirements for personalized viruses are easily
      managed in the context of a clinical trial following the directives from the
      study protocol.

PMID- 30228947
TI  - IMiDs mobilize acute myeloid leukemia blasts to peripheral blood through
      downregulation of CXCR4 but fail to potentiate AraC/Idarubicin activity in
      preclinical models of non del5q/5q- AML.
AB  - Treatment for acute myeloid leukemia (AML) remains suboptimal and many patients
      remain refractory or relapse upon standard chemotherapy based on nucleoside
      analogs plus anthracyclines. The crosstalk between AML cells and the BM stroma is
      a major mechanism underlying therapy resistance in AML. Lenalidomide and
      pomalidomide, a new generation immunomodulatory drugs (IMiDs), possess
      pleiotropic anti-leukemic properties including potent immune-modulating effects
      and are commonly used in hematological malignances associated with intrinsic
      dysfunctional BM such as myelodysplastic syndromes and multiple myeloma. Whether
      IMiDs may improve the efficacy of current standard treatment in AML remains
      understudied. Here, we have exploited in vitro and in vivo preclinical AML models
      to analyze whether IMiDs potentiate the efficacy of AraC/Idarubicin-based
      standard AML chemotherapy by interfering with the BM stroma-mediated
      chemoresistance. We report that IMiDs do not exert cytotoxic effects on either
      non-del5q/5q- AML cells nor BM-MSCs, but they enhance the immunomodulatory
      properties of BM-MSCs. When combined with AraC/Idarubicin, IMiDs fail to
      circumvent BM stroma-mediated resistance of non-del5q/5q- AML cells in vitro and
      in vivo but induce robust extramedullary mobilization of AML cells. When
      administered as a single agent, lenalidomide specifically mobilizes non-del5q/5q-
      AML cells, but not healthy CD34+ cells, to peripheral blood (PB) through specific
      downregulation of CXCR4 in AML blasts. Global gene expression profiling supports
      a migratory/mobilization gene signature in lenalidomide-treated non-del5q/5q- AML
      blasts but not in CD34+ cells. Collectively, IMiDs mobilize non-del5q/5q- AML
      blasts to PB through CXCR4 downregulation, but fail to potentiate AraC/Idarubicin
      activity in preclinical models of non-del5q/5q- AML.

PMID- 30228949
TI  - Clinically-Relevant Rapamycin Treatment Regimens Enhance CD8+ Effector Memory T
      Cell Function In The Skin and Allow their Infiltration into Cutaneous Squamous
      Cell Carcinoma.
AB  - Patients receiving immunosuppressive drugs to prevent organ transplant rejection
      exhibit a greatly increased risk of developing cutaneous squamous cell carcinoma
      (SCC). However, not all immunosuppressive drugs confer the same risk. Randomised,
      controlled trials demonstrate that switching renal transplant recipients
      receiving calcineurin inhibitor-based therapies to mammalian target of rapamycin
      (mTOR) inhibitors results in a reduced incidence of de novo SSC formation, and
      can even result in the regression of pre-existing premalignant lesions. However,
      the contribution played by residual immune function in this setting is unclear.
      We examined the hypotheses that mTOR inhibitors promote the enhanced
      differentiation and function of CD8+ memory T cells in the skin. Here, we
      demonstrate that the long-term oral administration of rapamycin to achieve
      clinically-relevant whole blood drug target thresholds, creates a "low rapamycin
      dose" environment in the skin. While both rapamycin and the calcineurin inhibitor
      tacrolimus elongated the survival of OVA-expressing skin grafts, and inhibited
      short-term antigen-specific CD8+ T cell responses, rapamycin but not tacrolimus
      permitted the statistically significant infiltration of CD8+ effector memory T
      cells into UV-induced SCC lesions. Furthermore, rapamycin uniquely enhanced the
      number and function of CD8+ effector and central memory T cells in a model of
      long-term contact hypersensitivity provided that rapamycin was present during the
      antigen sensitization phase. Thus, our findings suggest that patients switched to
      mTOR inhibitor regimens likely experience enhanced CD8+ memory T cell function to
      new antigen-challenges in their skin, which could contribute to their lower risk
      of de novo SSC formation and regression of pre-existing premalignant lesions.

PMID- 30228950
TI  - Inhibition of RON kinase potentiates anti-CTLA-4 immunotherapy to shrink breast
      tumors and prevent metastatic outgrowth.
AB  - The advent of immune checkpoint blockade as a new strategy for immunotherapy has
      changed the outlook for many aggressive cancers. Although complete tumor
      eradication is attainable in some cases, durable clinical responses are observed
      only in a small fraction of patients, underlining urgent need for improvement. We
      previously showed that RON, a receptor tyrosine kinase expressed in macrophages,
      suppresses antitumor immune responses, and facilitates progression and metastasis
      of breast cancer. Here, we investigated the molecular changes that occur
      downstream of RON activation in macrophages, and whether inhibition of RON can
      cooperate with checkpoint immunotherapy to eradicate tumors. Activation of RON by
      its ligand, MSP, altered the gene expression profile of macrophages drastically
      and upregulated surface levels of CD80 and PD-L1, ligands for T-cell checkpoint
      receptors CTLA-4 and PD-1. Genetic deletion or pharmacological inhibition of RON
      in combination with anti-CTLA-4, but not with anti-PD-1, resulted in improved
      clinical responses against orthotopically transplanted tumors compared to single
      agent treatment groups, resulting in complete tumor eradication in 46% of the
      animals. Positive responses to therapy were associated with higher levels of T
      cell activation markers and tumor-infiltrating lymphocytes. Importantly, co
      inhibition of RON and anti-CTLA-4 was also effective in clearing metastatic
      breast cancer cells in lungs, resulting in clinical responses in nearly 60% of
      the mice. These findings suggest that RON inhibition can be a novel approach to
      potentiate responses to checkpoint immunotherapy in breast cancer.

PMID- 30228951
TI  - Proteinase-nicked IgGs: an unanticipated target for tumor immunotherapy.
AB  - The host immune system adopts multiple mechanisms involving antibodies to
      confront cancer cells. Accordingly, anti-tumor mAbs have become mainstays in
      cancer treatment. However, neither host immunity nor mAb therapies appear capable
      of controlling tumor growth in all cases. Structural instability of IgG was
      overlooked as a factor contributing to immunosuppression in the tumor
      microenvironment. Recently, physiological proteinases were identified that
      disable IgG immune effector functions. Evidence shows that these proteinases
      cause localized IgG impairment by selective cleavage of a single IgG peptide bond
      in the hinge-region. The recognition of IgG cleavage in the tumor
      microenvironment provides alternatives for tumor immunotherapy.

PMID- 30228952
TI  - Systematic identification of cancer-specific MHC-binding peptides with RAVEN.
AB  - Immunotherapy can revolutionize anti-cancer therapy if specific targets are
      available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may
      enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo
      antigens generated by protein-coding missense mutations. Here, we describe an
      algorithm and user-friendly software named RAVEN (Rich Analysis of Variable gene
      Expressions in Numerous tissues) that automatizes the systematic and fast
      identification of CSG-encoded peptides highly affine to Major Histocompatibility
      Complexes (MHC) starting from transcriptome data. We applied RAVEN to a dataset
      assembled from 2,678 simultaneously normalized gene expression microarrays
      comprising 50 tumor entities, with a focus on oligo-mutated pediatric cancers,
      and 71 normal tissue types. RAVEN performed a transcriptome-wide scan in each
      cancer entity for gender-specific CSGs, and identified several established CSGs,
      but also many novel candidates potentially suitable for targeting multiple cancer
      types. The specific expression of the most promising CSGs was validated in cancer
      cell lines and in a comprehensive tissue-microarray. Subsequently, RAVEN
      identified likely immunogenic CSG-encoded peptides by predicting their affinity
      to MHCs and excluded sequence identity to abundantly expressed proteins by
      interrogating the UniProt protein-database. The predicted affinity of selected
      peptides was validated in T2-cell peptide-binding assays in which many showed
      binding-kinetics like a very immunogenic influenza control peptide. Collectively,
      we provide an exquisitely curated catalogue of cancer-specific and highly MHC
      affine peptides across 50 cancer types, and a freely available software
      (https://github.com/JSGerke/RAVENsoftware) to easily apply our algorithm to any
      gene expression dataset. We anticipate that our peptide libraries and software
      constitute a rich resource to advance anti-cancer immunotherapy.

PMID- 30228953
TI  - H3K4me3 mediates the NF-kappaB p50 homodimer binding to the pdcd1 promoter to
      activate PD-1 transcription in T cells.
AB  - PD-1 is a co-repressive receptor that curbs T cell activation and thereby serves
      as a protection mechanism against autoimmunity under physiological conditions.
      Under pathological conditions, tumor cells express PD-L1 as an adaptive resistant
      mechanism to suppress PD-1+ T cells to evade host immunosurveillance. PD-1
      therefore is a key target in cancer immunotherapy. Despite the extensive studies
      of PD-1 expression regulation, the pdcd1 transcription machinery and regulatory
      mechanisms are still not fully understood. We report here that the NF-kappaB p50
      homodimer is a transcription regulator of PD-1 in activated T cells. A putative
      kappaB sequence exists at the pdcd1 promoter. All five NF-kappaB Rel subunits are
      activated in activated T cells. However, only the p50 homodimer directly binds to
      the kappaB sequence at the pccd1 promoter in CD4+ and CD8+ T cells. Deficiency in
      p50 results in reduced PD-1 expression in both CD4+ and CD8+ T cells in vitro.
      Using an in vivo mixed bone marrow chimera mouse model, we show that p50
      regulates PD-1 expression in a cell-intrinsic way and p50 deficiency leads to
      decreased PD-1 expression in both antigen-specific CD4+ and CD8+ T cells in vivo.
      The expression levels of H3K4me3-specific histone methyltransferase increased
      significantly, resulting in a significant increase in H3K4me3 deposition at the
      pdcd1 promoter in activated CD4+ and CD8+ T cells. Inhibition of H3K4me3
      significantly decreased p50 binding to the pdcd1 promoter and PD-1 expression in
      a T cell line. Our findings determine that the p50-H3K4me3 axis regulates pdcd1
      transcription activation in activated T cells.

PMID- 30228955
TI  - Inflammation drives nitric oxide synthase 2 expression by gammadelta T cells and
      affects the balance between melanoma and vitiligo associated melanoma.
AB  - The high expression of inducible nitric oxide synthase (NOS2) by myeloid-derived
      suppressor cells (MDSCs) is a key mechanism of immune evasion in cancer. Recently
      we reported that NOS2 is also expressed by gammadelta T cells in melanoma,
      contributing to their polarization towards a pro-tumor phenotype. The molecular
      mechanisms underlying regulation of NOS2 expression in tumor-induced gammadelta T
      cells remain unexplored. By using the model of mice transgenic for the ret
      oncogene (Ret mice) that develops a spontaneous metastatic melanoma, we evidence
      that interleukin (IL)-1beta and IL-6 drive NOS2 expression in gammadelta T cells.
      Indeed, their in vivo neutralization lessens the gammadelta T cell capacity to
      produce not only NOS2, but also IL-17 involved in the recruitment of MDSCs at the
      primary tumor site. The treatment also delayed tumor cell dissemination and
      induced vitiligo in a significant proportion of Ret mice. Interestingly, Ret mice
      developing a less aggressive melanoma, characterized by the spontaneous
      development of a concomitant autoimmune vitiligo, exhibit a weaker concentration
      of inflammatory cytokines and a reduction of tumor infiltrating gammadelta T
      cells expressing NOS2, when compared to Ret mice without any signs of vitiligo.
      Overall our results support that the level of inflammation at the tumor site
      regulates NOS2 expression by gammadelta T cells and the development of vitiligo
      associated melanoma.

PMID- 30228954
TI  - Non-thermal plasma induces immunogenic cell death in vivo in murine CT26
      colorectal tumors.
AB  - Immunogenic cell death is characterized by the emission of danger signals that
      facilitate activation of an adaptive immune response against dead-cell antigens.
      In the case of cancer therapy, tumor cells undergoing immunogenic death promote
      cancer-specific immunity. Identification, characterization, and optimization of
      stimuli that induce immunogenic cancer cell death has tremendous potential to
      improve the outcomes of cancer therapy. In this study, we show that non-thermal,
      atmospheric pressure plasma can be operated to induce immunogenic cell death in
      an animal model of colorectal cancer. In vitro, plasma treatment of CT26
      colorectal cancer cells induced the release of classic danger signals. Treated
      cells were used to create a whole-cell vaccine which elicited protective immunity
      in the CT26 tumor mouse model. Moreover, plasma treatment of subcutaneous tumors
      elicited emission of danger signals and recruitment of antigen presenting cells
      into tumors. An increase in T cell responses targeting the colorectal cancer
      specific antigen guanylyl cyclase C (GUCY2C) were also observed. This study
      provides the first evidence that non-thermal plasma is a bone fide inducer of
      immunogenic cell death and highlights its potential for clinical translation for
      cancer immunotherapy.

PMID- 30228956
TI  - Aspergillus flavus endocarditis in an immunocompetent child. Case report.
AB  - Fungal endocarditis (FE) is a rare infection in pediatrics which accounts for 5%
      of the cases of infective endocarditis. This pathology affects immunosuppressed
      patients in a greater proportion. We present an immunocompetent 7- year-old
      female with a history of multiple cardiac surgeries who developed fungal
      endocarditis due to Aspergillus flavus. The histology study showed liquefactive
      necrosis and septate hyphae of Aspergillus sp type. The clinical outcome was
      favorable and the ambulatory follow-up after 12 months showed no new
      complications.

PMID- 30228957
TI  - Bowel sounds in the chest: An uncommon presentation of adult hernia.
AB  - We report a case of a 65-year-old male, who presented with respiratory complaints
      of cough and breathlessness, managed initially as respiratory tract infection.
      However, the patient did not improve, and a thorough examination and imaging
      revealed herniation of a gut segment into the thorax. The patient was operated
      and respiratory symptoms improved dramatically.

PMID- 30228959
TI  - A case of paroxysmal atrioventricular block-induced cardiac arrest.

PMID- 30228960
TI  - Hypertrophic cardiomyopathy: Ischemia progressing to ventricular fibrillation.

PMID- 30228958
TI  - Metazoan parasites of California sea lions (Zalophus californianus): A new data
      and review.
AB  - The population of California sea lion Zalophus californianus (CSL) has steadily
      increased during the last several decades. Despite extensive research addressing
      CSL biology and ecology performed during the last decades, there has been a
      minimal number of published papers documenting their parasite fauna. Our
      objective was to analyze the actual list of the metazoan parasites reported from
      CSLs and add new data on the age-related differences in the prevalence and
      biodiversity of the parasite community. There have been 33 species recorded but
      this study considers only 24 of them valid. Among them, 11 species are specific
      parasites of CSLs and 13 species are not specific. Additional species represent
      accidental infections or misidentifications. In total, 6653 helminths and 847
      mites were collected and identified from 34 CSLs for this study. Six species of
      nematodes, Anisakis simplex sensu lato s. l. (prevalence 41%; intensity 7.6),
      Contracaecum ogmorhini s. l. (38%; 269.6), Pseudoterranova decipiens s. l. (29%;
      33), P. azarazi (9%; 2.7), Acanthocheilonema odendhali (15%; 3.5) and
      Parafilaroides decorus were found. Two species of cestodes, Diphyllobothrium sp.
      (38%; 8.5) and Anophryocephalus sp. (15%; 14.6) represent novel undescribed
      species. Two species of trematodes, Apophallus zalophi (18%; 19.7) and
      Zalophotrema hepaticum (12%; 39.2), and five species of acanthocephalans,
      Corynosoma obtuscens (68%; 100.8), C. strumosum (53%; 4.6), Andracantha
      phalacrocoracis (3%; 1), Andracantha sp. (9%; 4.3) and Profilicollis altmani (6%;
      8.5) were found. Mites Orthohalarchne attenuata (prevalence 85%) were found in
      the nasal cavity, while O. diminuata (21%) parasitized in the trachea and
      bronchi. The highest levels of infection with nematodes and trematodes were found
      in adult CSLs (3-16 years old), whereas the highest level of infection with
      acanthocephalans was found in young CSLs (pups and yearlings).

PMID- 30228961
TI  - Atypical inferoseptal accessory pathway connection associated with an aneurysm of
      the coronary sinus: Insight from a three-dimensional combined image of
      electroanatomic mapping and computed tomography.

PMID- 30228962
TI  - Cryoablation of distal right atrial appendage tachycardia focus using
      intracardiac echocardiography and no fluoroscopy: Improved outcomes with modern
      technology.

PMID- 30228963
TI  - Right ventricular lead perforation through the septum, left ventricle, and
      pleura, managed by an open surgical approach.

PMID- 30228964
TI  - T-wave oversensing due to left ventricle-only pacing in cardiac resynchronization
      therapy optimization algorithm.

PMID- 30228965
TI  - Unusual case of late dislodgment of a superior vena cava coil.

PMID- 30228966
TI  - Inappropriate shock from delayed T-wave oversensing by a subcutaneous implantable
      cardioverter-defibrillator after septal myectomy for hypertrophic cardiomyopathy.

PMID- 30228967
TI  - Noninvasive detection of atrial fibrillation in cryptogenic stroke: Contribution
      of a new e-cardiology device.

PMID- 30228968
TI  - Paroxysmal 1:1 narrow complex tachycardia: What is the mechanism?

PMID- 30228969
TI  - Relevance of electrical connectivity between the coronary sinus and the left
      atrial appendage for the intentional electrical isolation of the left atrial
      appendage in treating persistent atrial fibrillation: Insights from the LEIO-AF
      study.

PMID- 30228970
TI  - Subvalvular His bundle pacing for pseudo-pacemaker syndrome and mitral
      regurgitation.

PMID- 30228971
TI  - Beauty and the beat: A complicated case of multifocal ectopic Purkinje-related
      premature contractions.

PMID- 30228972
TI  - Termination of tachycardia with resolution of left bundle branch block: What is
      the mechanism?

PMID- 30228973
TI  - The influence of His bundle pacing on tricuspid valve functioning using three
      dimensional echocardiography.

PMID- 30228974
TI  - Fourteen new mutations of BCKDHA, BCKDHB and DBT genes associated with maple
      syrup urine disease (MSUD) in Malaysian population.
AB  - Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic
      disorder. This disorder is usually caused by mutations in any one of the genes;
      BCKDHA, BCKDHB and DBT, which represent E1alpha, E1beta and E2 subunits of the
      branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, respectively. This
      study presents the molecular characterization of 31 MSUD patients. Twenty one
      mutations including 14 new mutations were identified. The BCKDHB gene was the
      most commonly affected (45.2%) compared to BCKDHA gene (16.1%) and DBT gene
      (38.7%). In silico webservers predicted all mutations were disease-causing. In
      addition, structural evaluation disclosed that all new missenses in BCKDHA,
      BCKDHB and DBT genes affected stability and formation of E1 and E2 subunits.
      Majority of the patients had neonatal onset MSUD (26 of 31). Meanwhile, the new
      mutation; c.1196C > G (p.S399C) in DBT gene was noted to be recurrent and found
      in 9 patients. Conclusion: Our findings have expanded the mutational spectrum of
      the MSUD and revealed the genetic heterogeneity among Malaysian MSUD patients. We
      also discovered the p.S399C from DBT gene was noted as a recurrent mutation in
      Malay community and it suggested the existence of common and unique mutation in
      Malay population.

PMID- 30228975
TI  - Analysis of GBE1 mutations via protein expression studies in glycogen storage
      disease type IV: A report on a non-progressive form with a literature review.
AB  - Background: Glycogen storage disease type IV (GSD IV), caused by GBE1 mutations,
      has a quite wide phenotypic variation. While the classic hepatic form and the
      perinatal/neonatal neuromuscular forms result in early mortality, milder
      manifestations include non-progressive form (NP-GSD IV) and adult polyglucosan
      body disease (APBD). Thus far, only one clinical case of a patient with compound
      heterozygous mutations has been reported for the molecular analysis of NP-GSD IV.
      This study aimed to elucidate the molecular basis in a NP-GSD IV patient via
      protein expression analysis and to obtain a clearer genotype-phenotype
      relationship in GSD IV. Case presentation: A Japanese boy presented
      hepatosplenomegaly at 2 years of age. Developmental delay, neurological symptoms,
      and cardiac dysfunction were not apparent. Observation of hepatocytes with
      periodic acid-Schiff-positive materials resistant to diastase, coupled with
      resolution of hepatosplenomegaly at 8 years of age, yielded a diagnosis of NP-GSD
      IV. Glycogen branching enzyme activity was decreased in erythrocytes. At 13 years
      of age, he developed epilepsy, which was successfully controlled by
      carbamazepine. Molecular analysis: In this study, we identified compound
      heterozygous GBE1 mutations (p.Gln46Pro and p.Glu609Lys). The branching
      activities of the mutant proteins expressed using E. coli were examined in a
      reaction with starch. The result showed that both mutants had approximately 50%
      activity of the wild type protein. Conclusion: This is the second clinical report
      of a NP-GSD IV patient with a definite molecular elucidation. Based on the
      clinical and genotypic overlapping between NP-GSD IV and APBD, we suggest both
      are in a continuum.

PMID- 30228977
TI  - A Statewide Model for Assisting Nursing Home Residents to Transition Successfully
      to the Community.
AB  - Minnesota's Return to Community Initiative (RTCI) is a novel, statewide
      initiative to assist private paying nursing home residents to return to the
      community and to remain in that setting without converting to Medicaid. The
      objective of this manuscript is to describe in detail RTCI's development and
      design, its key operational components, and characteristics of its clients and
      their care outcomes. Data on client characteristics and outcomes come from the
      Minimum Data Set, staff assessments of clients and caregivers, and Medicaid
      eligibility files. Most clients transitioned by the RTCI had entered the nursing
      facility from a hospital. Clients overwhelmingly wanted to return to the
      community and fit a health and functional profile making them good candidates for
      community discharge. Most clients went to a private residence, living alone or
      with a spouse; yet, adult children were the most frequent caregivers. At one year
      of follow-up 76% of individuals were alive and living in the community and only a
      small percentage (8.2%) had converted to Medicaid. The RTCI holds promise as a
      successful model for states to adopt in assisting individuals who are at risk to
      become long stay nursing home residents instead to return to the community.

PMID- 30228976
TI  - Molecular Pathogenesis of Nonalcoholic Steatohepatitis- (NASH-) Related
      Hepatocellular Carcinoma.
AB  - The proportion of obese or diabetic population has been anticipated to increase
      in the upcoming decades, which rises the prevalence of nonalcoholic fatty liver
      disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH).
      Recent evidence indicates that NASH is the main cause of chronic liver diseases
      and it is an important risk factor for development of hepatocellular carcinoma
      (HCC). Although the literature addressing NASH-HCC is growing rapidly, limited
      data is available about the etiology of NASH-related HCC. Experimental studies on
      the molecular mechanism of HCC development in NASH reveal that the carcinogenesis
      is relevant to complex changes in signaling pathways that mediate cell
      proliferation and energy metabolism. Genetic or epigenetic modifications and
      alterations in metabolic, immunologic, and endocrine pathways have been shown to
      be closely related to inflammation, liver injury, and fibrosis in NASH along with
      its subsequent progression to HCC. In this review, we provide an overview on the
      current knowledge of NASH-related HCC development and emphasize molecular
      signaling pathways regarding their mechanism of action in NASH-derived HCC.

PMID- 30228978
TI  - Spatial Directionality Found in Frontal-Parietal Attentional Networks.
AB  - Research in last few years on neurophysiology focused on several areas across the
      cortex during cognitive processing to determine the dominant direction of
      electrical activity. However, information about the frequency and direction of
      episodic synchronization related to higher cognitive functions remain unclear.
      Our aim was to determine whether neural oscillations carry perceptual information
      as spatial patterns across the cortex, which could be found in the scalp EEG of
      human subjects while being engaged in visual sensory stimulation. Magnitude
      squared coherence of neural activity during task states that "finger movement
      with Eyes Open (EO) or Eyes Wandering (EW)" among all electrode combinations has
      the smallest standard deviation and variations. Additionally, the highest
      coherence among the electrode pairs occurred between alpha (8-12 Hz) and beta (12
      16 Hz) ranges. Our results indicate that alpha rhythms seem to be regulated
      during activities when an individual is focused on a given task. Beta activity,
      which has also been implicated in cognitive processing to neural oscillations, is
      seen in our work as a manner to integrate external stimuli to higher cognitive
      activation. We have found spatial network organization which served to classify
      the EEG epochs in time with respect to the stimuli class. Our findings suggest
      that cortical neural signaling utilizes alpha-beta phase coupling during
      cognitive processing states, where beta activity has been implicated in shifting
      cognitive states. Significance. Our approach has found frontoparietal attentional
      mechanisms in shifting brain states which could provide new insights into
      understanding the global cerebral dynamics of intentional activity and reflect
      how the brain allocates resources during tasking and cognitive processing states.

PMID- 30228979
TI  - Microbiological Quality Assessment of Popular Fresh Date Samples Available in
      Local Outlets of Dhaka City, Bangladesh.
AB  - It is evident that date fruits provide a wide variety of essential nutrients
      which impart potential human health benefits. In Bangladesh, the popularity of
      date and its consumption surge few-fold during Ramadan among Muslims owing to the
      profound emotion related to religious belief that breaking of dawn-to-dusk
      fasting with dates is fulfilling a Sunnah. The present study aimed to explore the
      microbiological quality of the five most popular fresh date samples (Nagal,
      Dhapas, Boroi, Morium, and Tunisia) purchased from different locations of Dhaka
      City, Bangladesh. Among 25 samples tested, 23 were observed to carry 3.30-5.65
      Log CFU/gm aerobic bacteria and 3.30-5.36 Log CFU/gm yeasts and molds population.
      Coliform bacteria and Escherichia coli were not found in any of the samples
      analyzed in this study. However, except Nagal and Boroi from Mohammadpur and
      Mirpur, respectively, none of the samples were found safe to consume according to
      the microbiological grade recommended by Woolworths Quality Assurance Standard
      (WQAS), 2009, as fresh dates with microbial load can cause food poisoning or even
      foodborne intoxication. Date samples with less or no processing is responsible
      for this contamination which can be subsided and eliminated by appropriate
      handling and hygiene practices during postharvest processing.

PMID- 30228981
TI  - Respiratory Tract Infection: A Risk Factor for the Onset and Relapse of Adult
      Onset Minimal Change Disease in Southern China.
AB  - Aims/Introduction: Steroid resistance and frequent relapse are problems in the
      treatment of minimal change disease (MCD). However, epidemiological factors that
      influence steroid-resistant and relapse of MCD are rarely reported. This study
      evaluated potential factors that influence the onset and relapse of MCD and the
      epidemiological features of southern Chinese patients with adult-onset MCD.
      Patients and Methods: Patients with adult-onset MCD were included from the
      Affiliated Hospital of Guangdong Medical University, which is located in the
      southernmost part of China's mainland, between 2015 and 2016. Potential
      influencing factors were investigated. Results: Eighty-seven patients with
      incipient MCD were enrolled, and 85 of these patients were followed up; 71.8%
      (61/85) were steroid-sensitive and 28.2% (24/85) were steroid-resistant. In terms
      of seasonal distribution, the highest rate of incipient cases was in spring
      (39.1%, 34/87), which also showed a high rate of relapse cases (29.7%, 22/74).
      Among patients who were followed up for more than half a year and whose
      proteinuria completely resolved (69.4%, 59/85), 52.5% (31/59) were without
      relapse and 47.5% (28/59) were with relapse. Patients without relapse were older
      than those with relapse (P<0.05). Before disease onset, 20.7% (18/87) of patients
      with incipient MCD were diagnosed with infection, including 94.5% (17/18) with
      respiratory tract infection. Fourteen patients in complete remission
      posttreatment developed an infection before relapse, including 85.7% (12/14) with
      respiratory tract infection. Conclusion: Steroid resistance and frequent relapse
      are current challenges for the treatment of adult-onset MCD in southern China,
      and respiratory tract infection may be a risk factor for onset and relapse.
      Additionally, younger patients with MCD tend to have more frequent relapse.

PMID- 30228980
TI  - Analysis of Transcription Factor-Related Regulatory Networks Based on
      Bioinformatics Analysis and Validation in Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) accounts for a significant proportion of liver
      cancer, which has become the second most common cause of cancer-related mortality
      worldwide. To investigate the potential mechanisms of invasion and progression of
      HCC, bioinformatics analysis and validation by qRT-PCR were performed. We found
      237 differentially expressed genes (DEGs) including EGR1, FOS, and FOSB, which
      were three cancer-related transcription factors. Subsequently, we constructed TF
      gene network and miRNA-TF-mRNA network based on data obtained from mRNA and miRNA
      expression profiles for analysis of HCC. We found that 42 key genes from the TF
      gene network including EGR1, FOS, and FOSB were most enriched in the p53
      signaling pathway. The qRT-PCR data confirmed that mRNA levels of EGR1, FOS, and
      FOSB all were decreased in HCC tissues. In addition, we confirmed that the mRNA
      levels of CCNB1, CCNB2, and CHEK1, three key markers of the p53 signaling
      pathway, were all increased in HCC tissues by bioinformatics analysis and qRT-PCR
      validation. Therefore, we speculated that miR-181a-5p, which was upregulated in
      HCC tissues, could regulate FOS and EGR1 to promote the invasion and progression
      of HCC by p53 signaling pathway. Overall, the study provides support for the
      possible mechanisms of progression in HCC.

PMID- 30228983
TI  - Effect of Ionizing Radiation on the Microbiological Safety and Phytochemical
      Properties of Cooked Malva sylvestris L.
AB  - Nowadays, recent studies have demonstrated that plant-derived foods were
      characterized by their richness in bioactive phytochemicals and their consumption
      has a protective effect for human health. The effects of ionizing radiation on
      phytochemical properties of cooked Malva sylvestris L. (Mallow) were
      investigated. Irradiation increased significantly (P<0.05) the total polyphenols
      and flavonoids content of cooked Mallow. Irradiation at 2 and 4 kGy doses
      resulted in a significant increase in the DPPH and ABTS radical-scavenging
      ability of cooked Mallow extracts. There was no significant change on
      carbohydrate, lipid, ash, and protein content. While the mineral composition of K
      and Na was affected slightly after irradiation, the amounts of Mg, P, Ca, Fe, Z,
      and Cu remain unaffected at 2 kGy and reduced slightly at 4 kGy. The
      antimicrobial activity was unaffected after irradiation. Postirradiation storage
      studies showed that the cooked irradiated Mallow was microbiologically safe even
      after 20 days of storage period. Sensory properties of cooked irradiated Mallow
      were unaffected by the treatment. This study supports that cooking process
      followed by gamma irradiation did not compromise the chemical composition and
      sensory characteristics of Mallow.

PMID- 30228982
TI  - A Comparison between Piezoelectric Devices and Conventional Rotary Instruments in
      Bone Harvesting in Patients with Lip and Palate Cleft: A Retrospective Study with
      Clinical, Radiographical, and Histological Evaluation.
AB  - Introduction: Orofacial clefts are congenital malformations characterized by an
      incomplete shaping of structures that separate the nasal from the oral cavity and
      can affect the right, left, or both sides. The aim of the present study is to
      assess, with clinical, radiographical, and histological evaluations, the efficacy
      of piezoelectric devices compared to traditional rotating instruments in the bone
      harvesting in patients with history of cleft. Materials and Methods: We have
      conducted a retrospective analysis on 20 patients with a history of orofacial
      clefts that were operated on from February 2014 to June 2017. The patients were
      divided into two groups: Group R in which bone graft was harvested using a burr
      and Group P in which the bone graft was obtained by a piezoelectric device. After
      a healing period of 8 months from the grafting procedure, clinical and
      radiographic evaluations were performed. Results and Discussion: The use of the
      piezoelectric devices in bone harvesting allows a slight improvement in the final
      volume. This supports a faster integration into the receiving site. Conclusions:
      The use of piezoelectric device in patients with history of orofacial cleft that
      needed bone graft represents a method to be taken into consideration because it
      has interesting advantages.

PMID- 30228984
TI  - Effect of Adenosine and Adenosine Receptor Antagonists on Retinal Muller Cell
      Inwardly Rectifying Potassium Channels under Exogenous Glutamate Stimulation.
AB  - The vitreousness of glaucoma subjects contains elevated glutamate, and excessive
      extracellular glutamate is toxic to retinal neurons. Therefore, glutamate
      clearance is potentially impaired in the retina of glaucoma subjects. Muller
      cells play an important role in maintaining low extracellular levels of
      neurotransmitters, such as glutamate. A better understanding of the cross-talk
      between adenosine and glutamate may provide a better characterization of the
      regulatory network in Muller cells. Here, Muller cells were purified from the rat
      retina on postnatal day 5 using the papain digestion method. Application of
      increasing concentrations of glutamate (0-20 mmol/L) caused a dose-dependent
      decrease in the expression levels of Kir4.1, Kir2.1, GLAST, and GS. Exogenous
      adenosine regulated Kir channels and subsequently promoted GLAST and GS
      expression levels in Muller cells under exogenous glutamate stimulation. These
      effects were partly dependent on adenosine receptors.

PMID- 30228985
TI  - Cinnamaldehyde Improves Lifespan and Healthspan in Drosophila melanogaster Models
      for Alzheimer's Disease.
AB  - Cinnamon extract has been reported to have positive effects in fruit fly and
      mouse models for Alzheimer's disease (AD). However, cinnamon contains numerous
      potential active compounds that have not been individually evaluated. The main
      objective of this study was to evaluate the impact of cinnamaldehyde, a known
      putative active compound in cinnamon, on the lifespan and healthspan of
      Drosophila melanogaster models for Alzheimer's disease, which overexpress Abeta42
      and MAPT (Tau). We found that cinnamaldehyde significantly improved the lifespan
      of both AD and non-AD flies. Cinnamaldehyde also improved the healthspan of AD
      flies overexpressing the Tau protein by improving climbing ability, evaluated by
      rapid iterative negative geotaxis (RING), and improving short-term memory,
      evaluated by a courtship conditioning assay. Cinnamaldehyde had no positive
      impact on the healthspan of AD flies overexpressing the Abeta42 protein.

PMID- 30228986
TI  - Do Patients with Second Primary Colorectal Cancer Hold the Similar Prognosis and
      Therapeutic Benefits as Those with Initial Primary Colorectal Cancer?
AB  - Aim: The objective is to compare the differences on prognosis and the therapeutic
      benefits between initial and second primary colorectal cancer (pCRC). Methods: A
      dataset containing 377,271 initial pCRC cases and 18,617 second pCRC cases from
      the National Cancer Institute's Surveillance, Epidemiology, and End Results
      (SEER) 1988-2015 was evaluated. Survival comparisons were made using the log-rank
      test. Cox proportional hazards models were used to assess the survival benefits.
      Results: The cancer-specific survival rate of patients with initial pCRC was
      significantly higher than that of patients with second pCRC (5-years survival
      rate: 64.85% vs. 60.22%, P<0.001). The Chi-square of stratified log rank for age
      at diagnosis was lower than that for primary site, pTNM stage, sex, race,
      histology, and grade (Chi-square=86.73). There were almost no differences on
      therapeutic benefits between patients with initial and second pCRC except that
      treatments with chemotherapy were significantly associated with longer survival
      rate compared with treatments without chemotherapy among stage III surgical
      initial and second primary left-sided colon cancers patients (HR=0.764 vs. 0.581;
      P for interaction =0.008). Conclusion: Patients with second pCRC have worse
      prognosis than those with initial pCRC primarily because of older age in the
      former group. The results evidenced that the therapeutic benefits on the
      prognosis for colorectal cancer were generally similar between patients with
      initial and second pCRC.

PMID- 30228987
TI  - Characterization of Detailed Audiological Features of Cytomegalovirus Infection:
      A Composite Cohort Study from Groups with Distinct Demographics.
AB  - Congenital cytomegalovirus (cCMV) infection is a common congenital infection that
      causes sensorineural hearing loss (SNHL). Despite its substantial impact on
      public health and cost burden, epidemiology and clinical features of CMV-related
      SNHL have never been reported in the Korean populations. This study investigated
      the detailed audiologic phenotypes of cCMV infection to see if a specific SNHL
      pattern is associated with a particular clinical setting. A total of 38 patients
      with cCMV infection were studied retrospectively. Patients were classified into
      three groups with distinct demographics: clinically driven diagnosis (n=17),
      routine newborn CMV screening according to the NICU protocols (n=10), or referral
      to ENT for cochlear implant (CI) (n=11). The incidence of cCMV infection was
      3.6%, showing 33.3% of SNHL among cCMV patients, 38% of asymmetric hearing loss,
      29% of late-onset hearing loss, and diverse severity spectrum in patients with
      CMV-related SNHL. CI recipients with CMV-related SNHL showed a significantly
      improved speech perception. Surprisingly, in 36.4 % of CI implantees, initial
      audiological manifestation was significant asymmetry of hearing thresholds
      between both ears, with better ear retaining significant residual hearing up to
      50dB. CMV turns out to be a significant etiology of SNHL, first to date reported
      in the Korean pediatric population. Analysis of audiologic phenotypes showed a
      very wide spectrum of SNHL and favorable CI outcomes in case of profound
      deafness. Especially for the patients with asymmetric hearing loss, close
      surveillance of hearing should be warranted and CI could be considered on the
      worse side first, based on the observation of rapid progression to profound
      deafness of better side.

PMID- 30228988
TI  - Drosophila Models of Human Disease.

PMID- 30228989
TI  - An Efficient Feature Selection Strategy Based on Multiple Support Vector Machine
      Technology with Gene Expression Data.
AB  - The application of gene expression data to the diagnosis and classification of
      cancer has become a hot issue in the field of cancer classification. Gene
      expression data usually contains a large number of tumor-free data and has the
      characteristics of high dimensions. In order to select determinant genes related
      to breast cancer from the initial gene expression data, we propose a new feature
      selection method, namely, support vector machine based on recursive feature
      elimination and parameter optimization (SVM-RFE-PO). The grid search (GS)
      algorithm, the particle swarm optimization (PSO) algorithm, and the genetic
      algorithm (GA) are applied to search the optimal parameters in the feature
      selection process. Herein, the new feature selection method contains three kinds
      of algorithms: support vector machine based on recursive feature elimination and
      grid search (SVM-RFE-GS), support vector machine based on recursive feature
      elimination and particle swarm optimization (SVM-RFE-PSO), and support vector
      machine based on recursive feature elimination and genetic algorithm (SVM-RFE
      GA). Then the selected optimal feature subsets are used to train the SVM
      classifier for cancer classification. We also use random forest feature selection
      (RFFS), random forest feature selection and grid search (RFFS-GS), and minimal
      redundancy maximal relevance (mRMR) algorithm as feature selection methods to
      compare the effects of the SVM-RFE-PO algorithm. The results showed that the
      feature subset obtained by feature selection using SVM-RFE-PSO algorithm results
      has a better prediction performance of Area Under Curve (AUC) in the testing data
      set. This algorithm not only is time-saving, but also is capable of extracting
      more representative and useful genes.

PMID- 30228990
TI  - Insecticide Resistance and Its Intensity in Populations of Malaria Vectors in
      Colombia.
AB  - Insecticide resistance in malaria vectors threatens malaria prevention and
      control efforts. In Colombia the three primary vectors, Anopheles darlingi, An.
      nuneztovari s.l., and An. albimanus, have reported insecticide resistance to
      pyrethroids, organophosphates, carbamates, and DDT; however, the insecticide
      resistance monitoring is not continuous, and the data on the prevalence of
      resistance is scarce and geographically limited. We describe the resistance
      levels and intensity of previously detected resistant populations among primary
      malaria vectors from the most endemic malaria areas in Colombia. The study was
      carried out in 10 localities of five states in Colombia. Bioassays were carried
      out following the methodology of CDC Bottle Bioassay using the discriminating
      concentration and in order to quantify the intensity the specimens were exposed
      to 2, 5, and 10X discriminating concentrations. Five insecticides were tested:
      deltamethrin, lambda-cyhalothrin, alpha-cypermethrin, permethrin, and DDT. The
      results provide evidence of low resistance intensity and resistance highly
      localized to pyrethroids and DDT in key malaria vectors in Colombia. This may not
      pose a threat to malaria control yet but frequent monitoring is needed to follow
      the evolution of insecticide resistance.

PMID- 30228991
TI  - Dynamic Expression of Genes Involved in Proteoglycan/Glycosaminoglycan Metabolism
      during Skin Development.
AB  - Glycosaminoglycans are important for cell signaling and therefore for proper
      embryonic development and adult homeostasis. Expressions of genes involved in
      proteoglycan/glycosaminoglycan (GAG) metabolism and of genes coding for growth
      factors known to bind GAGs were analyzed during skin development by microarray
      analysis and real time quantitative PCR. GAG related genes were organized in six
      categories based on their role in GAG homeostasis, viz. (1) production of
      precursor molecules, (2) production of core proteins, (3) synthesis of the
      linkage region, (4) polymerization, (5) modification, and (6) degradation of the
      GAG chain. In all categories highly dynamic up- and downregulations were observed
      during skin development, including differential expression of GAG modifying
      isoenzymes, core proteins, and growth factors. In two mice models, one
      overexpressing heparanase and one lacking C5 epimerase, differential expression
      of only few genes was observed. Data show that during skin development a highly
      dynamic and complex expression of GAG-associated genes occurs. This likely
      reflects quantitative and qualitative changes in GAGs/proteoglycans, including
      structural fine tuning, which may be correlated with growth factor handling.

PMID- 30228992
TI  - Outcomes of Limited Open Achilles Repair Using Modified Ring Forceps.
AB  - Background: The optimal treatment of acute Achilles tendon ruptures remains
      controversial. When surgical repair is undertaken, the reported rate of
      infections and wound-healing complications ranges from 2% to 5%. Meta-analyses
      have demonstrated that minimally invasive approaches have equivalent rerupture
      rates, a significantly lower risk of superficial infections, and higher patient
      satisfaction rates compared with traditional open Achilles repair techniques.
      Purpose: To review the clinical outcomes of acute, limited open Achilles tendon
      repair using modified ring forceps and to analyze functional results using foot
      and ankle-specific outcome measures. Study Design: Case series; Level of
      evidence, 4. Methods: The clinical records of 32 consecutive patients (mean age,
      44 years) with 33 acute Achilles tendon ruptures were retrospectively reviewed.
      All patients underwent limited open repair with modified ring forceps through a 2
      to 3-cm midline incision. Suture placement into the tendon stumps was guided
      using a pair of ring forceps bent 30 degrees . Three No. 2 nonabsorbable sutures
      were placed in the proximal and distal segments, the tendon ends were
      reapproximated, and the sutures were tied to secure the tendon. Outcomes from a
      10-cm visual analog scale (VAS), the Foot and Ankle Ability Measure (FAAM), and
      the Victorian Institute of Sport Assessment-Achilles (VISA-A) were assessed.
      Results: At final follow-up (mean, 42.1 months [range, 6-90 months]), 31 of 32
      patients (33 Achilles tendons) reported no pain in their Achilles, with a mean
      Achilles VAS score of 0.7 +/- 4.2 of 100. The mean postoperative VISA-A score was
      82.3 +/- 19.5 of 100. The mean FAAM activities of daily living and sports
      subscores were 96.5% +/- 5.2% and 85.1% +/- 21.2%, respectively. Regarding
      current functional level, 19 of 33 tendons (57.6%) were rated as "normal," 10
      (30.3%) as "nearly normal," and 4 (12.1%) as "abnormal"; none were rated as
      "severely abnormal." There was 1 case (3.0%) of a superficial infection; there
      were no cases of deep infections, sural neuritis, or reruptures. The cost of the
      modified ring forceps technique is 5.3 to 12.1 times less than commercially
      available devices. Conclusion: Limited open Achilles repair with modified ring
      forceps provides an economical repair with excellent pain relief, favorable
      functional outcomes, and a very low complication rate at midterm follow-up.

PMID- 30228993
TI  - Treatment of Capitellar Osteochondritis Dissecans With a Novel Regenerative
      Technique: Case Report of 3 Patients After 4 Years.

PMID- 30228994
TI  - Integration of genome-wide mRNA and miRNA expression, and DNA methylation data of
      three cell lines exposed to ten carbon nanomaterials.
AB  - We present data derived from an exposure experiment in which three cell-lines
      representative of cell types of the respiratory tissue (epithelial type-I A549,
      epithelial type-II BEAS-2B, and macrophage THP-1) have been exposed to ten
      different carbon-based nanomaterials for 48 h. In particular, we provide: genome
      wide mRNA and miRNA expression, and DNA methylation; gene tables, containing
      information on the aberrations induced in these three genomic data layers at the
      gene level; mechanism of action (MOA) maps representing the comparative
      functional alteration induced in each cell line and each exposure.

PMID- 30228995
TI  - A comprehensive annotation for the root-knot nematode Meloidogyne incognita
      proteome data.
AB  - Root-knot nematodes are devastating pathogens of crop plants. The draft genome of
      southern root-knot nematode Meloidogyne incognita was published in 2008 and
      additional genome and transcriptome data became available later on. However, lack
      of a publically available annotation for M. incognita genome and transcriptome(s)
      limits the use of this data for functional and comparative genomics by the
      interested researchers. Here we present a comprehensive annotation for the M.
      incognita proteome data available at INRA Meloidogyne Genomic Resources page
      (https://meloidogyne.inra.fr/Downloads/Meloidogyne-incognita-V2-2017) and
      European Nucleotide Archive (ENA) (accession number: ERP009887) using a multi
      pronged approach.

PMID- 30228996
TI  - Relative importance of wildlife and livestock transmission route of brucellosis
      in southwestern Uganda.
AB  - The data in brief provides a descriptive summary of the field data collected
      using Eco-health approach in order to support local effort aimed at creating
      information base for taking evidence-based decisions, especially in regard to
      wildlife conservation outside protected area and range resource management. The
      data were collected between June 2012 and July 2014 on a range of issues
      including wild animals, livestock, household income and cost of diseases control
      in cattle. In a nutshell the data article shows spatial pattern of a declining
      brucellosis prevalence in cattle linked to animal population density with
      increasing distance away from the Lake Mburo National Park (LMNP) boundary in
      southwestern Uganda. It is the trend of animal distribution in private land that
      the pastoralist communities perceived as influencing economic losses associated
      with diseases affecting cattle production. The pastoralists strongly believe that
      wild ungulates grazing with cattle outside the park on a daily basis present a
      potential risk of disease transmission which adversely affects their cherished
      source of livelihood. This article refers to "Brucellosis in cattle and micro
      scale spatial variability of pastoral household income from dairy production in
      south western Uganda. Acta tropica", Acta Tropica, 2018.

PMID- 30228997
TI  - Ultraviolet radiation rate in Mashhad, Iran.
AB  - Todays, Climate change can be effect on the intensity of ultraviolet (UV)
      radiation and cause of many human diseases. In this cross-sectional study,
      changes of the intensity of UV ray were associated with the changes in latitude
      and longitude, height, climatic conditions, natural and human-made artifacts.
      Given that the highest radiation intensity was at the beginning of the summer,
      the radiation rate of UV ray in Mashhad was measured in the summer using a Hagner
      radiometer, the UV-A model. The radiation rate of the UV ray was determined in
      2000 stations, which were 5 km far from each other. Data were analyzed using
      SPSSv16 software, T-test, and ANOVA tests. The results of this study showed that
      the radiation rate of UV ray in Mashhad was 0.49+/-0.143 mSv per year. The
      findings showed that latitudinal and longitudinal changes did not have a
      significant effect on the intensity of UV radiation (P > 0.001). The changes in
      the height above the sea level influenced the irradiance rate of UV and
      increasing the height above the sea level raised UV radiation (P < 0.001). Human
      artifacts significantly changed the rate of UV radiation (P < 0.001). Cloudy,
      semi-cloudy and sunny conditions had the most effects on UV radiation (P <
      0.001). The results revealed that the average rate of UV ray in Mashhad was below
      the global standard (10 W/m2 for UV ray), and traffic in open air could not be
      risky.

PMID- 30228998
TI  - Data on cryptogamic biota in relation to heavy metal concentrations in soil.
AB  - The data presented here are related to the research article entitled "Cryptogamic
      communities as a useful bioindication tool for estimating the degree of soil
      pollution with heavy metals" (Rola and Osyczka, 2018) [1]. These data concern the
      relationships between epigeic cryptogamic biota and heavy metal concentrations in
      soil of areas associated with Zn-Pb industry. The presence of particular species
      and coverage of lichens and bryophytes as well as soil chemical parameters in
      relation to three different soil pollution classes and five habitat types are
      provided. Included data could be used to compare cryptogamic community structure
      and pollutant concentration levels with other Zn-Pb polluted areas.

PMID- 30228999
TI  - Scanning electron microscopy as a tool for evaluating morphology of amyloid
      structures formed on surface plasmon resonance chips.
AB  - We demonstrate the use of Scanning Electron microscopy (SEM) in combination with
      Surface Plasmon Resonance (SPR) to probe and verify the formation of amyloid and
      its morphology on an SPR chip. SPR is a technique that measures changes in the
      immobilized weight on the chip surface and is frequently used to probe the
      formation and biophysical properties of amyloid structures. In this context it is
      of interest to also monitor the morphology of the formed structures. The SPR chip
      surface is made of a layer of gold, which represent a suitable material for
      direct analysis of the surface using SEM. The standard SPR chip used here (CM5
      chip, GE Healthcare, Uppsala, Sweden) can easily be disassembled and directly
      analyzed by SEM. In order to verify the formation of amyloid fibrils in our
      experimental conditions we analyzed also in-solution produced structures by using
      Transmission Electron Microscopy (TEM). For further details and experimental
      findings, please refer to the article published in Journal of Molecular Biology,
      (Brannstrom K. et al., 2018) [1].

PMID- 30229000
TI  - Survey data on Vietnamese retail investors' trading behavior and their
      psychological and behavioral patterns.
AB  - The data article describes self-assessments of 621 Vietnamese retail investors on
      their trading behavior, psychological attributes and socio-demographic
      characteristics. The dataset was obtained from a randomized survey of 3144
      Vietnamese participants on financial attitudes and practice that has been used in
      Phan et al. [5]. A supplemental material data contains the full text, codes and
      numerical values of survey instruments. Discussion of theoretical frameworks and
      the development of hypothesis and measurement of survey variables are found in
      the associated research article [6].

PMID- 30229001
TI  - Computational Fluid Dynamics data for improving freeze-dryers design.
AB  - Computational Fluid Dynamics (CFD) can be used to simulate different parts of an
      industrial freeze-drying equipment and to properly design them; in particular
      data concerning the freeze-dryer chamber and the duct connecting the chamber with
      the condenser, with the valves and vanes eventually present are given here, and
      can be used to understand the behavior of the apparatus allowing an improved
      design. Pilot and large scale freeze-drying chambers have been considered; data
      of a detailed simulation of a complete pilot scale apparatus, including duct and
      condenser, are included. Data on conductance of an empty duct with different L/D
      ratio, on disk valves with different geometry, and on mushroom valve are
      presented. Velocity, pressure, temperature and composition fields are reported on
      selected planes for chambers and valves. Results of dynamic simulations are also
      presented, to evaluate possible performance of monitoring devices in the chamber.
      Some further data, with detailed interpretation and discussion of the presented
      data can be found in the related research article by Barresi et al. [1] and
      Marchisio et al. [2].

PMID- 30229002
TI  - Data for indirect load case estimation of ice-induced moments from shaft line
      torque measurements.
AB  - During ice navigation, blade measurements of ice-induced moments on ship
      propellers, are challenged by the harsh operating environment. To overcome this
      problem, shaft line measurements are performed inboard, and the required
      propeller loads are subsequently estimated using a dynamic model and the solution
      of an inverse problem. The inverse problem is mathematically ill-posed and
      requires the determination of the ice-induced moment on the propeller blades from
      shaft line measurements. Full-scale torsional response data is presented as
      calculated from indirect strain measurements on the shaft line of a polar supply
      and research vessel. The vessel operated on a 68-day voyage between Cape Town and
      Antarctica and spent almost 11 days in sea ice with observed concentrations above
      90% and a maximum thickness of 3 m. Data for five ice-induced load cases are
      presented, including the shaft torque from indirect measurements and the
      estimated ice-induced moment, which is obtained by solving an ill-posed inverse
      problem. The ice-induced moments on the propeller are obtained by approximating
      the drive-train as a viscously damped, elastic lumped mass model. The ice-induced
      moment is then determined through existing approaches to solving the ill
      conditioned inverse problem. The lumped mass model is presented along with
      algorithms to solve the inverse problem, including truncated singular value
      decomposition, truncated generalized singular value decomposition and Tikhonov's
      method. The resulting time series data for the inversely calculated ice-induced
      moments is published to provide industry with load cases for ice-going propulsion
      design.

PMID- 30229003
TI  - Analysis of selected crime data in Nigeria.
AB  - Crime is an act that brings about offences and it is punishable under the law.
      Major crimes in Nigeria include rape, kidnapping, murder, burglary, fraud,
      terrorism, robbery, cyber-crimes, bribery and corruption, money laundering and so
      on. According to the statistics released by the Nigerian National Bureau of
      Statistics in 2016, Lagos, Abuja, Delta, Kano, Plateau, Ondo, Oyo, Bauchi,
      Adamawa and Gombe States made the top ten list of states with high number of
      crimes. Crime is an important topic and it is of interest to us because of the
      consequences and penalties it attracts (which ranges from fine to death). This
      data article contains the partial analysis (both descriptive and inferential) of
      crime data set obtained between 1999 and 2013. The aim of the study is to show
      the pattern and rate of crime in Nigeria based on the data collected and to show
      the relationships that exist among the various crime types. Analyzing this data
      set can provide insight on crime activities within Nigeria.

PMID- 30229004
TI  - Cancer risks from chest radiography of young adults: A pilot study at a health
      facility in South West Nigeria.
AB  - The recommendation of chest radiography for school admission and employment
      purposes should be discouraged due to the risks of radiation especially cancer
      induction. It is therefore imperative to keep diagnostic radiation doses as low
      as possible. This dataset presents the entrance surface dose, effective dose,
      bone marrow dose, breast dose, lung dose and the incidence cancer risks from
      chest radiography of 40 young adult females. The mean incidence cancer risk to
      participants is 1: 20,000 for solid cancers. The data revealed the significant
      factors influencing the entrance surface dose and incidence cancer risks.

PMID- 30229005
TI  - Data on characterization of crude bio-oils, gaseous products, and process water
      produced from hydrothermal liquefaction of eight different algae.
AB  - The characterization of products produced from hydrothermal liquefaction of algal
      biomass is helpful to better understand the effect of different kinds of raw
      materials on the properties of the product fractions. The data presented in this
      article are related to the research article entitled "Integration of hydrothermal
      liquefaction and supercritical water gasification for the improvement of energy
      recovery from algal biomass" (Duan et al., 2018) [1]. In this data article, the
      compositions of gaseous products produced from hydrothermal liquefaction of eight
      different algae feedstocks at 350  degrees C for 60 min were analyzed by gas
      chromatography. The molecular and elemental compositions of the crude bio-oils
      produced from hydrothermal liquefaction of eight different algae feedstocks at
      350  degrees C for 60 min were analyzed by comprehensive two-dimensional gas
      chromatography-time-of-flight mass spectrometry and organic elemental analyzer.
      The color of aqueous phases before and after they were subjected to supercritical
      water gasification was recorded by a high-resolution camera.

PMID- 30229006
TI  - Data on composition and production rate of dental solid waste and associated
      management practices in Qaem Shahr, Iran 2016.
AB  - This report investigates to analyse the production of waste in dental offices of
      Qaem Shahr city. In this study, from 120 dental offices in Qaem Shahr city, 21
      offices were selected through random sampling. Sampling taken from 3 offices in 3
      consecutive working days (on Sundays, Mondays and Tuesdays). The components were
      classified into three groups based on their specificity and potential. Total
      annual waste produced in Dentist Offices in Qaem Shahr city is 557.80 kg. In
      dental office, the amount of biohazard, chemical and pharmaceutical and domestic
      type wastes were 64.10, 2.70 and 33.20 respectively. Production percentages of
      biohazard, the highest weighted mean for potentially biohazard (155.25+/-0.63 g)
      and the lowest for chemical and pharmaceutical (6.35+/-1.85 g).

PMID- 30229007
TI  - Data from proteomic analysis of bovine Longissimus dorsi muscle associated with
      intramuscular fat content.
AB  - The proteomic data presented in this article are associated with the research
      article entitled "Longissimus dorsi muscle label-free quantitative proteomic
      reveals biological mechanisms associated with intramuscular fat deposition"
      published in Journal of Proteomics [1]. In this article, we characterized the
      proteomic profile of bovine Longissimus dorsi muscle from Nelore steers and
      identified differentially abundant proteins associated with the intramuscular fat
      (IMF) content. An integrated transcriptome-assisted label-free quantitative
      proteomic approach by High Definition Mass Spectrometry (HDMSE) was employed to
      identify and quantify the proteins. A functional enrichment analysis using the
      differentially abundant proteins list was performed to understand the biological
      processes involved in IMF deposition. Moreover, to explore and clarify the
      biological mechanisms that influence IMF content, the mRNA data for the same
      trait from Cesar and collaborators [2] obtained by RNA-sequencing technology was
      compared with proteomic data. The mRNA data is deposited in the European
      Nucleotide Archive (ENA) repository (EMBL-EBI), under accession PRJEB13188.

PMID- 30229008
TI  - Qualitative and quantitative analysis of the proautophagic activity of Citrus
      flavonoids from Bergamot Polyphenol Fraction.
AB  - Bergamot Polyphenol Fraction (BPF(r)) is a natural mixture of Citrus flavonoids
      extracted from processed bergamot fruits. It has been shown to counteract
      cardiovascular risk factors and to prevent liver steatosis in rats and patients.
      Hepatic effects of BPF correlate with its ability to stimulate liver autophagy.
      Six aglyconic flavonoids have been identified in the proautophagic fraction of
      the hydrolysis product of BPF (A-BPF): naringenin, hesperetin, eridictyol,
      diosmetin, apigenin and luteolin. We report here the output parameters of high
      resolution mass spectrometry analysis of these flavonoids and chemical structures
      of their parent compounds. The second set of data shows the proautophagic
      activity of BPF flavonoids in a hepatic cell line HepG2 analyzed by a flow
      cytometry approach. The method is based on the red to green fluorescence
      intensity ratio analysis of DsRed -LC3- GFP, which is stably expressed in HepG2
      cells. Proportional analysis of ATG indexes allowed us to address a relative
      contribution of individual compounds to the proautophagic activity of the A-BPF
      mixture and evaluate if the effect was additive. Qualitative analysis of ATG
      indexes compared the effects of flavonoids at equal concentrations in the
      presence and absence of palmitic acid and chloroquine. The Excel files reporting
      the analysis of flow cytometry data are available in the public repository.

PMID- 30229009
TI  - Synchronized drowsiness monitoring and simulated driving performance data under
      50-hr sleep deprivation: A double-blind placebo-controlled caffeine intervention.
AB  - This paper presents the 60-s time-resolution segment from our 50-h total sleep
      deprivation (TSD) dataset (Aidman et al., 2018) [1] that captures minute-by
      minute dynamics of driving performance (lane keeping and speed variability) along
      with objective, oculography-derived drowsiness estimates synchronised to the same
      1-min driving epochs. Eleven participants (5 females, aged 18-28) were randomised
      into caffeine (administered in four 200 mg doses via chewing gum in the early
      morning hours) or placebo groups. Every three hours they performed a 40 min
      simulated drive in a medium fidelity driving simulator, while their drowsiness
      was continuously measured with a spectacle frame-mounted infra-red alertness
      monitoring system. The dataset covers 15 driving periods of 40 min each, and thus
      contains over 600 data points of paired data per participant. The 1-min time
      resolution enables detailed time-series analyses of both time-since-wake and time
      on-task performance dynamics and associated drowsiness levels. It also enables
      direct examination of the relationships between drowsiness and task performance
      measures. The question of how these relationships might change under various
      intervention conditions (caffeine in our case) seems worth further investigation.

PMID- 30229010
TI  - Data on a thermostable enzymatic one-pot reaction for the production of a high
      value compound from l-arabinose.
AB  - The dataset presented in this article is related to the research article entitled
      "One-pot, two-step transaminase and transketolase synthesis of l-gluco-heptulose
      from l-arabinose" (Bawn et al., 2018 in press) [1]. This article presents data on
      initial experiments that were carried out to investigate new thermostable
      transketolase (TK) activities with l-arabinose. Transaminase (TAm) sequences from
      an in-house library of thermophilic strains were analyzed to compare homologies
      to characterized TAms with desired activity. DNA and amino acid sequences are
      presented for all the enzymes investigated. Calibration curves for products of
      the TK and TAm reactions are also presented along with chromatographic analysis
      of the various one-pot reactions.

PMID- 30229012
TI  - Data on molecular identification, phylogeny and in vitro characterization of
      bacteria isolated from maize rhizosphere in Cameroon.
AB  - Bacteria, which establish positive interactions with plant roots, play a key role
      in agricultural environments and are promising for their potential use in
      sustainable agriculture. Many of these mutualistic bacteria provide benefits to
      plant hosts by facilitating soil mineral nutrient uptake, protecting plants from
      biotic and abiotic stresses and producing substances that promote growth. The
      dataset presented here, is related to the publication entitled "Community
      structure and plant growth-promoting potential of cultivable bacteria isolated
      from Cameroon soil" (Tchuisseu et al., 2018) [1]. The data provide an extended
      analysis of the occurrence, taxonomical affiliation and functional traits of
      bacterial groups isolated from the rhizosphere of maize in Cameroon at different
      taxonomical levels, using a combination of molecular/bioinformatics tools and in
      vitro studies. Bacteria were isolated from maize rhizosphere soil. Isolated
      bacteria were identified using the 16s rRNA gene sequencing and phylogenetic
      analyses. All strains were characterized for their potential of salinity
      tolerance and growth promotion (phosphate solubilization, nifH gene presence and
      siderophore production) in order to select efficient bacterial strains for
      designing biological fertilizer exploitable for agriculture under specific stress
      conditions of the country. The data will be valuable for further studies on plant
      associated bacteria in Cameroon, which are still largely unexplored.

PMID- 30229011
TI  - Data on the test-retest reproducibility of streamline counts as a measure of
      structural connectivity.
AB  - These data provide estimations of test-retest reproducibility of streamline
      counts based on diffusion weighted imaging (DWI) data using a global tractography
      algorithm in a sample of young healthy adults. Data on descriptive statistics and
      factorial analyses of within-session and between-session reproducibility in terms
      of intra-class correlation coefficients for the absolute agreement between
      measurements are provided. The effect of several exemplary methodological
      parameters pertaining to different steps along the tractography processing
      pipeline on reproducibility are considered. These data are related to the
      research article entitled 'Probing the reproducibility of quantitative estimates
      of structural connectivity derived from global tractography' (Schumacher et al.,
      Neuroimage, 175 (2018) 215-229).

PMID- 30229013
TI  - Data on diversity and abundance of zooplanktons along the northern part of the
      Persian Gulf, Iran.
AB  - In this data article, we aimed to evaluate and compare the biological diversity
      and relative abundance of zooplankton communities in 3 different areas along the
      northern part of the Persian Gulf in 3 different seasons. Data showed that
      Centropages spp and Fish larvae were the highest and lowest species among the
      groups identified in summer in Lavare Saheli and Nakhle Taghi with relative
      abundances of 87% and 2.7% respectively. In winter, Cyphonautes larvae and
      Corycaeus spp. were the highest and lowest species in Kangan and Lavare Saheli
      with relative abundances of 57.1% and 1.88%, respectively. Also Decapoda larvae
      spp. and Gastropoda larvae were the highest and lowest species in spring in
      Kangan with relative abundances of 62.5% and 4.7% respectively. Data may serve as
      benchmarks for other groups working in the field of pollution control, aquatic
      ecosystem, and toxicology.

PMID- 30229014
TI  - Data on Fourier transform-infrared of Cosmos caudatus Kunth. tissues analyzed
      with chemometric analysis.
AB  - In this dataset, we differentiate four different tissues of Cosmos caudatus Kunth
      (leaves, flowers, stem and root) obtained from UKM Bangi plot, based on Fourier
      transform-infrared spectroscopy. Different tissues of C. caudatus demonstrated
      the position and intensity of characteristic peaks at 4000-450 cm-1. Principal
      component analysis (PCA) shows three main groups were formed. The samples from
      leaves and flowers were found to be clustered together in one group, while the
      samples from stems and roots were clustered into two separate groups,
      respectively. This data provides an insight into the fingerprint identification
      and distribution of metabolites in the different organs of this species.

PMID- 30229015
TI  - Electricity prices in Italy: Data registered during photovoltaic activity
      interval.
AB  - Data we present in this article are related to the research article by Bertolini
      M., D'Alpaos C. and Moretto M. "Do Smart Grids boost investments in domestic PV
      plants? Evidence from the Italian electricity market"(Bertolini et al., 2018)
      [1]. The dataset is an elaboration of historical spot prices provided by the
      Italian Gestore dei Mercati Energetici (GME) and gives information about average
      prices registered during the day, when photovoltaic (PV) plants are - on average 
      expected to produce energy. Prices are stated in ?/MWh.

PMID- 30229016
TI  - Daily rainfall nearest neighbor pattern using point data series in Iran.
AB  - In this data study, assessment of daily rainfall nearest neighbor's patterns
      (DRBBP) was described in Iran. This article presents some spatial patterns of
      daily rainfall nearest neighbor's patterns for Iran from 170 stations and 31195
      rainfall points by comparing ordinary kriging techniques based on the forecast
      models. For the nearest neighbor's patterns of the daily rainfall, rainfall data
      series of 1975-2014 was employed to estimate the point data of daily rainfall.
      The statistical properties were analyzed to indicate an increase in dispersed
      variability patterns of daily rainfall in Iran. Dispersed patterns were selected
      as the best nearest neighbor's models to model daily rainfall variability. The
      data results will help climatologists and hydrologists in model assessment and
      planning of natural environment in Iran.

PMID- 30229017
TI  - Statistical analysis of frequencies of opponents' eliminations in Royal Rumble
      wrestling matches, 1988-2018.
AB  - The datasets and their analyses presented in this paper revealed some frequencies
      of opponents' eliminations by entrance or order of elimination in Royal Rumble
      wrestling matches from 1988 to 2018. The frequency of eliminations by the order
      of entrant is quite different from order of eliminations. Statistical methods,
      algorithms and machine learning methods can be applied to the raw data to obtain
      more hidden trend not included in this article.

PMID- 30229018
TI  - Data on CaO and eggshell catalysts used for biodiesel production.
AB  - This research investigated the production of biodiesel from soybean oil
      (transesterification process) using pure calcium oxide and calcium oxide obtained
      from eggshell as heterogeneous catalysts. Uncalcined eggshell and calcined
      eggshell catalysts produced were analysed using XRF and XRD spectrometers. The
      processing parameters considered during the transesterification of the soybean
      were methanol/oil mole ratio, catalyst concentration and reaction time and their
      effects on biodiesel yield were evaluated. Reaction temperature of 60  degrees C
      and stirring rate of 450 rpm (revolution per minute) were kept constant. As a
      result of calcination, XRF analysis revealed an increase in CaO percentage
      composition of eggshell catalyst from 96% to 97%. Also, the biodiesel yields
      obtained revealed similar performance patterns for both the calcined eggshell
      catalyst and the pure CaO catalyst.

PMID- 30229019
TI  - Recovery rate data for silicon nitride nanoparticle isolation using sodium
      polytungstate density gradients.
AB  - The average recovery rate of silicon nitride nanoparticles isolated from serum
      using the method detailed in previous article "A novel method for isolation and
      recovery of ceramic nanoparticles and metal wear debris from serum lubricants at
      ultra-low wear rate" (Lal et al., 2016) [1] was tested gravimetrically by
      weighing particles doped into serum before and after the isolation process. An
      average recovery rate of approximately 89.6% (+/- 7.1 SD) was achieved.

PMID- 30229020
TI  - Experimental data on the air-sea energy fluxes at the tropical coastal ocean in
      the southern South China Sea.
AB  - Air-sea flux exchanges influence the climate condition and the global carbon
      moisture cycle. It is imperative to understand the fundamentals of the natural
      systems at the tropical coastal ocean and how the transformation takes place over
      the time. Hence, latent and sensible heat fluxes, microclimate variables, and
      surface water temperature data were collected using eddy covariance instruments
      mounted on a platform at a tropical coastal ocean station from November 2015 to
      October 2017. The research data is to gain the needful knowledge of the energy
      exchanges in the tropical climatic environment to further improve predictive
      algorithms or models. Therefore, it is intended that this data report will offer
      appropriate information for the Monsoonal, and diurnal patterns of latent (LE)
      and sensible (H) heats and hence, establish the relationship between microclimate
      variables on the energy fluxes at the peninsular Malaysian tropical coastal
      ocean.

PMID- 30229022
TI  - An overview of use, knowledge and perceptions of the Internet in Spain.
AB  - The present data article offers a dataset about the use, knowledge, attitudes,
      and perceptions of the Internet in the entire of Spanish territory (16-65+). The
      data is achieved through biennial surveys in 2011 and 2013. This allows observing
      the evolution of assessments, the perception of use and penetration that
      different digital services have in the Spanish society. The paper includes some
      descriptive data that shows characteristic of internet access and Internet
      consumption among internet users and non-users over 16 years old.

PMID- 30229021
TI  - A study of staff's awareness and attitudes towards the importance of household
      hazardous wastes (HHW) management (A Case Study of Kermanshah University of
      Medical Sciences, Kermanshah, Iran).
AB  - The present study aimed to assess the levels of staff's awareness and attitudes
      towards the importance of household hazardous wastes (HHW) management at
      Kermanshah University of Medical Sciences (KUMS), Kermanshah, Iran. The awareness
      and attitudes were measured using a researcher-made questionnaire, which was then
      completed by 200 personnel at KUMS with different responsibilities. Finally, the
      data were then analyzed using the SPSS Statistical Software Version 21.0. The
      results of the present study showed that the average of awareness for man and
      woman was obtained 19.59 +/- 3.53 and 19.88 +/- 3.33, respectively. While, the
      attitude for them was 58.66 +/- 9.5 and 61.25 +/- 9.8, respectively. In terms of
      variable "job type", the highest score about awareness and attitude was related
      to physician (20.45 +/- 2.41) and nurse (61.8 +/- 9.2) jobs respectively. The
      highest level of awareness was for those with a diploma degree, while in term of
      attitude the maximum score was obtained for those who were undergraduate and
      bachelor degree. Based on age group, minimum and maximum score of awareness were
      related to 44-53 and 44-53 years, respectively. While in term of attitude were 54
      65 and 34-43 years, respectively. According to results, it is suggested that
      households be trained in separating, recycling, collecting, transporting and
      disposing of HHWs in accordance with health standards with the aim of providing,
      maintaining and improving the health of families, societies and environment. It
      should be noted that prevention of adverse environmental effects of hazardous
      waste is a priority, which can be realized through applying proper management
      methods.

PMID- 30229023
TI  - Data for analyzing drilling fluid ability to effectively achieve hole cleaning
      for high shear and low shear rates.
AB  - Rheological models such as Bingham Plastic or Power law models depict fluid
      behavior with points of the rheological relation which correspond to higher shear
      rates, but these models are fairly easy to solve for their specific descriptive
      parameters. Lower rpm (and hence shear rate), could be used to improve the
      performance and understanding of drilling mud at the lower shear rates prevailing
      in the wellbore. These data can be utilized in validating these rheological
      models and the essence of Equivalent Circulating Density (ECD) calculation in
      analyzing pressure drop in annular hole cleaning.

PMID- 30229024
TI  - The data on exploratory factor analysis of factors influencing employees
      effectiveness for responding to crisis in Iran military hospitals.
AB  - The article presents the data on the exploratory analysis of factors involved in
      employees' effectiveness for responding to crisis in Iran's military hospitals.
      This research was a descriptive exploratory study. The statistical population
      included the 561 medical and nonmedical staff of three military hospitals. Two
      researcher-made questionnaires were used to collect data, and reliability and
      validity of the questionnaires were confirmed. The exploratory factor analysis
      (EFA) method was used to classify, clarify, and explain study factors and the
      infrastructural structure. At the end, 473 questionnaires were found appropriate
      for the final analysis. Based on results of the exploratory factor analysis
      (EFA), 8 criteria were identified as the main factors involved in employees'
      effectiveness for responding to crisis. According to Friedman test results,
      organizational factors were the most important factors influencing employees'
      effectiveness with a mean score of 3.76 of 5. Responding to crisis was the most
      important variable factor involved response to crisis with a mean score of 3.74
      of 5.

PMID- 30229026
TI  - Data on recovery rates and external morphologies of zircon grains from mechanical
      and electrical pulverization of rock samples.
AB  - In this data article, we provide information on the recovery rate and scanning
      electron microscope (SEM) images of the external morphology of zircon grains
      separated from two rock samples (AS3 and TEMORA 2) using both mechanical and
      electrical pulverization systems. The data in this article are related to the
      research article entitled "New insight into disturbance of U-Pb and trace-element
      systems in hydrothermally altered zircon via SHRIMP analyses of zircon from the
      Duluth Gabbro" (Takehara et al., 2018) [1]. Zircons from these two rock samples
      are widely used as reference materials for U-Pb dating by micro-beam techniques.
      Rock samples with nearly equal weights were pulverized by both methods, and the
      recovered zircon grains were then concentrated using conventional mineral
      separation methods. Weights of the products at each step in the mineral
      separation process were measured, and finally the recovery rates of the heavy and
      non-magnetic minerals, including zircon, were calculated.

PMID- 30229025
TI  - Oxygen absorption data of multilayer oxygen scavenger-polyester films with
      different layouts.
AB  - Oxygen absorption measurements in continuous regard active multilayer films with
      different layouts, all incorporating a PET/Oxygen scavenger (OS) layer, operating
      as active O2 barrier, inserted between two PET inert layers, acting as passive O2
      barrier. The data set is related to "Transport properties of multilayer active
      PET films with different layers configuration" by Apicella et al. (2018) [1]. A
      set of four multilayer films, with different relative thickness of the active and
      inert layers, was produced using a laboratory scale co-extrusion cast-film
      equipment and was analyzed in terms of oxygen scavenging performance. Single
      layer active and inert layers were also produced for comparison. The results have
      shown a longer exhaustion time for all the active multilayer films, respect to
      the active monolayer one. Moreover, at constant thickness of the active layer,
      the exhaustion time increases by increasing the thickness of the inert layers,
      whereas, at constant thickness of the inert layers, the residual oxygen
      concentration decreases by increasing the thickness of the active layer.

PMID- 30229027
TI  - Magnetic and structural data used to monitor the alloying process of mechanically
      alloyed Fe80Ni20.
AB  - In the last decades, much attention was given to mechanical alloying as it proved
      to be a cheap and easy way to produce (even metastable) nanostructured alloys.
      Especially Fe-Ni alloys have been studied intensely due to their technological
      and scientific importance. The MA process, however, is not fully understood.
      Furthermore, remanence properties of Fe80Ni20 are not well known. In our article
      "Monitoring the alloying process of mechanically synthesized Fe80Ni20through
      changes in magnetic properties (DOI: j.jallcom.2017.10.090, Volk et al., 2018)
      [1])" we investigated structural and magnetic properties of the intermediate and
      final alloys. Elemental Fe (99.5%) and Ni (99.7%) powders were filled in a 80 ml
      zirconia vials together with 3 mm zirconia milling balls and milled at 400 PRM
      with a planetary ball mill (Fritsch Pulverisette Premium 7). By subsampling the
      product at 14 different times during the process, the data presented here shows
      how crystalline structure (X-ray diffraction) and magnetic properties, induced as
      well as remanent, of the metastable Fe80Ni20 change during the mechanical
      synthesis.

PMID- 30229028
TI  - Methylation data from Pseudotaxus chienii obtained using methylation-dependent
      restriction-site associated DNA sequencing.
AB  - Pseudotaxus chienii is an endangered coniferous plant that is endemic to China.
      Because P. chienii is sessile and has a long life cycle, its options for
      responding to drastic or rapid changes in climate are limited. To survive
      locally, P. chienii must be able to adapt, and the species shows variations in
      leaf size along an environmental gradient from east to west. It is important to
      determine whether this phenotypic variation is driven by DNA methylation.
      Therefore, we performed a preliminarily survey using methylation-dependent
      restriction-site associated DNA sequencing (MethylRAD) to investigate the
      methylation status of three P. chienii individuals from heterogeneous ecological
      niches. In total, 372,611 CCGG tags and 726,332 CCHGG tags were obtained. The
      rate of high quality methylation tags for a specific site in the genome varied
      from 42.31% (Gxdms3-4) to 50.01% (Jxbj3-4) and 50.18% (Zjdxg3-6). The level of
      CCHGG methylation (16.63%) was higher than that of CCGG (13.60%), which may be
      why P. chienii has low levels of phenotypic variation. The methylation data can
      be accessed using the Sequence Read Archive (SRA) database (SRP128155).

PMID- 30229029
TI  - Terrestrial LiDAR-derived non-destructive woody biomass estimates for 10 hardwood
      species in Virginia.
AB  - This article contains data related to the research article entitled "Assessing
      terrestrial laser scanning for developing non-destructive biomass allometry"
      (Stovall et al., 2018 [1]) and presents 258 terrestrial LiDAR-derived estimates
      of tree volume and biomass. The terrestrial LiDAR acquisitions were completed in
      the Center for Tropical Forest Science - Forest Global Earth Observatory (CTFS
      ForestGEO) plot in Front Royal, Virginia, USA. The data includes tree diameter at
      breast height (DBH), total tree height, tree length (correcting for tree lean),
      average wood density, estimated wood volume, and dry weight or biomass for all
      trees. These data were used to develop aboveground biomass models [1] and the
      reader is referred to this study for additional information, interpretation, and
      reflection on applying this data.

PMID- 30229030
TI  - Computation of human health risk in surface water in Ado-Odo Ota, Ogun State,
      Nigeria.
AB  - Heavy metals find their way into surface and groundwater due to degrading
      environmental conditions, and as such consistent monitoring to avoid the adverse
      health implications associated with the consumption of polluted water is
      required. This study examined the concentrations for Lead (Pb), Nickel (Ni), Zinc
      (Zn), Chromium (Cr), Cadmium (Cd), Copper (Cu) and Arsenic (As) in the Surface
      water of River Balogun in Ota, Ogun State, Nigeria during the wet season and
      estimated the human health risk resulting from prolonged consumption by children
      and adult of dissimilar age groups without treatment. Although there were
      persistent occurrence of Nickel (Ni), Copper (Cu), Zinc (Zn) and Arsenic (As) in
      all stations sampled, the health risk assessment conducted revealed that both
      population groups are more likely to be affected by high concentration levels of
      Arsenic than any other Heavy metal present.

PMID- 30229032
TI  - Experimental data of designing an optimal system for storage, collection and
      transfer of household waste in the GIS environment: A case study of Tehran,
      district 22, Iran.
AB  - This study was conducted to correctly manage the system of storage, collection
      and transfer of wastes in district 22, Tehran. After reviewing existing methods,
      an optimal system was designed in the GIS environment and appropriate solutions
      were suggested. Analytical Hierarchy Process (AHP) method was used. After
      extracting result criteria, these criteria were provided to 15 experts and
      managers by means of a Delphi questionnaire. Screening of the criteria was done
      using the criterion importance graph; a necessary condition to apply criteria and
      sub-criteria, is having at least half the numerical value of each vertical and
      horizontal vector. The results of the study showed that the most important
      criterion associated with the selection of waste transfer station is "distance
      from residential houses" with a final weight of 0.341. "Suitable traffic
      conditions" and "lack of noise pollution" are the next important criteria with
      weights of 0.259 and 0.118, respectively. Finally, "non-destruction of
      recreational facilities" was chosen as the least important (weight of 0.03).
      Transfer in this district is also 100% mechanized. At the district level, there
      are 10 garbage trucks, of which 7 collect during night and 3 during day. Given
      per capita of the district, it takes about 10 min to collect each ton of waste.
      In general, in order to investigate and plan specific methods in the study
      district, using Geographic Information System, the location of reservoirs in
      residential and commercial districts has been determined and suggested with a
      coefficient of 0.75.

PMID- 30229033
TI  - Data on shale-water based drilling fluid interaction for drilling operation.
AB  - The shale dispersion test (rolling test) is a common procedure that is used to
      measure the interactions between drilling fluids and shales. The shale rolling
      test depends on the moisture content of the shale, the shale composition, the
      viscosity of the test fluid, the rotation speed of the rollers, and the test
      temperature. The rheological behavior of the test fluid has the strongest
      influence on test results. The data was generated experimentally, shale samples
      from Agbada formation Niger-Delta was used. These shale samples were cored at a
      depth of 2000 ft and 3400 ft. Water based mud that will minimize shale dispersion
      and swelling of shale was formulated. The dispersion test was conducted, and it
      involves exposing a weighted quantity of sized shale to the formulated mud in
      roller-oven. This test is used to design fluids and screen the effectiveness of
      inhibitor additives to maintain the integrity of the cuttings and minimize the
      interaction of fluids with the shale sections during the drilling and completion
      operations. The swelling test was conducted and the linear expansion adopted
      because it is the most representative of the increase seen by the wellbore but
      was measured in the direction perpendicular to the bedding plane as this is the
      direction of swelling into the wellbore.

PMID- 30229031
TI  - Datasets on factors influencing trading on pedestrian bridges along Ikorodu road,
      Lagos, Nigeria.
AB  - The survey data was obtained from a study that investigated factors responsible
      for the patronage of the traders on the pedestrian bridges along Ikorodu road,
      Lagos state, Nigeria. Survey research was adopted for this investigation while
      data were primarily sourced. The sample frame adopted for this study was the
      average total number of people using the pedestrian bridges per day along Ikorodu
      road was estimated as 240,380, while the sample size was 384, based on Cochran's
      sample size formula. The convenience, non-probability sampling technique was used
      for the survey. Data were analyzed using descriptive statistics (frequency
      tables) and inferential statistics techniques (factor analysis for data reduction
      and categorization, communalities of variables and KMO) while Likert scale was
      used as a means of measurement. The datasets can be considered in the commerce
      and environmental policies of Lagos State and Nigeria with a view to recommending
      policies that will encourage easy movement of people and the effective uses of
      the transport facilities.

PMID- 30229034
TI  - Data article on elemental and metabolomic-based alkaloidal composition in black
      pepper oleoresin using a positive ESI-mode LC-QToF and ICP-mass spectroscopy.
AB  - This paper contains data from the elemental and phytochemical profiling of black
      pepper oleoresin extracts using the LC-MS QToF and ICP-MS analysis. In recent
      years studies have shown the medicinal properties of extracts from these two
      cultivars of Piper nigrum. The medicinal properties are attributed to the
      presence of many secondary metabolites and mineral element in them. The
      phytochemical profiling was conducted using a Liquid Chromatography equipped with
      an electrospray time-of-flight mass spectrometer detectors. The mass spectrometer
      was equipped with an electrospray ionization sources operated in positive ion
      mode. The alkaloid compounds in the optimized black pepper extract were
      tentatively characterized in accordance with their ions' mass fragmentation.

PMID- 30229035
TI  - Data from quantitative proteomic analysis of lung adenocarcinoma and squamous
      cell carcinoma primary tissues using high resolution mass spectrometry.
AB  - Lung cancer is the leading cause of preventable death globally and is broadly
      classified into adenocarcinoma and squamous cell carcinoma. In this study, we
      carried out mass spectrometry based quantitative proteomic analysis of lung
      adenocarcinoma and squamous cell carcinoma primary tissue by employing the
      isobaric tags for relative and absolute quantitation (iTRAQ) approach. Proteomic
      data analyzed using SEQUEST algorithm resulted in identification of 25,998
      peptides corresponding to 4342 proteins of which 610 proteins were differentially
      expressed (>= 2-fold) between adenocarcinoma and squamous cell carcinoma. These
      differentially expressed proteins were further classified by gene ontology for
      their localization and biological processes. Pathway analysis of differentially
      expressed proteins revealed distinct alterations in networks and pathways in both
      adenocarcinoma and squamous cell carcinoma. We identified a subset of proteins
      that show inverse expression pattern between lung adenocarcinoma and squamous
      cell carcinoma. Such proteins may serve as potential markers to distinguish
      between the two subtypes. Mass spectrometric data generated in this study was
      submitted to the ProteomeXchange Consortium
      (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository
      with the dataset identifier PXD008700.

PMID- 30229036
TI  - Synthesis of reactive 1,3-diphenyl-6-aryl-substituted fulvene chromophores.
AB  - This data article describes a detailed synthetic strategy and experimental data
      for the synthesis of brominated fulvene chromophores as reactive
      precursors/monomers for conjugated organic materials. Metal-mediated coupling
      reactions of brominated fulvenes would result in conjugated small molecules or
      polymers that would find application as organic light emitting diodes (OLEDs) and
      photovoltaic (PV) applications.

PMID- 30229037
TI  - Statistical analyses on inverted perovskite solar cells employing non-fullerene
      based small molecule as a cathode interfacial layer.
AB  - In this data article, we present the influences of the solvent, concentration,
      and spin rates of 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))
      5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6
      b']dithiophene) (ITIC) material on the performances of perovskite solar cells
      (PSCs). The device parameters such as open-circuit voltage (Voc), short circuit
      current (Jsc), fill factor (FF), and power conversion efficiency (PCE) were
      measured with Keithley 2400 source meter unit under 100 mW/cm2 (AM 1.5 G). The
      data in this article describe the optimization of ITIC-based PSCs and are
      directly related to our research article "Non-fullerene-based small molecules as
      an efficient n-type electron transporting layers in inverted organic-inorganic
      halide perovskite solar cells" (Noh et al., Submitted for publication) [1].

PMID- 30229038
TI  - Raw high-speed schlieren footage of acoustic waves in air for subsequent
      computational analysis and audio recovery.
AB  - The dataset presented here comprises 79 raw, unprocessed video files obtained
      from the high-speed schlieren imaging of acoustic waves in air, each with a
      corresponding metadata file. The majority of the footage was recorded at 50,000
      frames per second, with each condition filmed for a duration of 20 ms. The
      dataset includes footage corresponding to a wide range of signals, in terms of
      waveform, frequency, and amplitude, as well as varied imaging parameters
      (exposure, frame rate, spatial resolution). This Data in Brief article is to
      accompany the research article "Visualization of acoustic waves in air and
      subsequent audio recovery with a high-speed schlieren imaging system:
      Experimental and computational development of a schlieren microphone" [1].

PMID- 30229039
TI  - Local and global response data from post-fire earthquake simulations of RC
      structural walls.
AB  - Data are provided from simulation studies of post-fire earthquake (PFE) of
      reinforced concrete (RC) structural walls. Local response data describe material
      peak temperatures and residual stiffness and strength, as well as quantification
      of the extent of seismic damage. Global response data provide load-deformation
      envelopes, as well as stiffness, strength, and deformation capacity. The data can
      support development of simplified modeling tools for PFE analysis of buildings,
      as well as to support development of and interpretation of future experimental
      tests. For further theory behind the modeling approach and full interpretation of
      the data, the reader is referred to the article entitled "Post-fire seismic
      behavior of reinforced concrete structural walls" (Ni and Birely, 2018) [1].

PMID- 30229040
TI  - Data on the scope of the literature on sustainable intensification 1997-2016:
      Bibliography, geography and practical approaches.
AB  - The data presented in this DiB article offers a full overview on the scientific
      sustainable intensification literature from 1997 to 2016. It consists of articles
      retrieved from the Scopus and the Web of Science databases that feature
      "Sustainable Intensification" (SI) as search term in title, abstract or author
      keywords. Information on bibliography, geographic focus and proposed sustainable
      intensification practices of each publication is recorded. The suggested
      sustainable intensification practices were assigned into 26 SI approaches
      constituting bundles of practices using a qualitative classification approach.
      The data is related to the research article entitled"Conceptualising fields of
      action for sustainable intensification. A systematic literature review and
      application to regional case studies" [1]. The information builds a baseline to
      assess the developments of the knowledge on SI and especially its practical
      implementation in depth. The database provides a comprehensive and structured
      overview of the SI literature and guidance for scholars and practitioners working
      on the topic.

PMID- 30229041
TI  - Data on physicochemical quality of drinking water in the rural area in
      Divandarreh county, Kurdistan, Iran.
AB  - Good quality of drinking water is very important in the maintenance of human
      health. The gathered data from the present work was used to evaluate the quality
      of drinking water resources in the rural villages of Divandarreh, Iran.
      Physicochemical quality of water was determined by a collection of 35 random
      samples during dry and rainy seasons in 2015. The APHA approach was used to
      determine the physicochemical parameters of the samples. The results showed that
      the average concentration of Ca, Mg, Na, K, Cl, SO4, TDS and TH during dry season
      was 85.64 mg/l, 13.41 mg/l, 34.11 mg/l, 2.8 mg/l, 9.9 mg/l, 45.7 mg/l, 326.06
      mg/l and 269.61 mg/l, respectively. Also, the average concentration of the
      parameters during rainy season was 77.3 mg/l, 18.27 mg/l, 30.3 mg/l, 1.9 mg/l,
      12.54 mg/l, 39 mg/l, 269.1 mg/l and 316.17 mg/l, respectively.

PMID- 30229042
TI  - Data on horizontal hydraulic conductivity of fine-grained soils of the former
      Lake Texcoco (Mexico).
AB  - This article contains data of the horizontal hydraulic conductivity of five
      different fine-grained soils of the former Lake Texcoco. The data were back
      calculated from excess pore pressure dissipation measurements collected at 119
      locations using piezocone tests (CPTu). The test campaign was part of the
      geotechnical survey performed for the construction of the New Mexico City
      International Airport (NAICM). Descriptive statistical parameters of each soil
      unit are presented and lognormal probability distributions are fitted to describe
      the natural variability of the horizontal hydraulic conductivity of this site.

PMID- 30229043
TI  - Protein X-ray crystallography of the 14-3-3zeta/SOS1 complex.
AB  - Activation of Ras-MAPK signaling regulates essential cellular functions; its
      aberration leads to irregular cell proliferation and differentiation (i.e.
      pancreatic cancer). Previously, it was revealed that the formation of the complex
      of the 14-3-3 protein and the Son of sevenless homolog 1 (SOS1) - one of the main
      actors of the Ras-MAPK cascade -, would represent a key-process to downstream the
      deviant Ra-MAPK signaling. In this data article we attempt to shed some light on
      the 3D structure, providing useful details about the crystallization process of
      the 14-3-3zeta dimer in complex with the 13-mer SOS1pS1161. The crystal structure
      is deposited at the Protein Data Bank with identifier 6F08. This Data in Brief
      article refers to "Structural characterization of 14-3-3zeta in complex with the
      human Son of sevenless homolog 1 (SOS1) (2018)."

PMID- 30229044
TI  - Survey datasets on organisational climate and job satisfaction among academic
      staff in some selected private universities in Southwest Nigeria.
AB  - This study attempts to establish the relationships that exist between the
      different variables of organizational climate and job satisfaction among academic
      staff in some selected private Universities in South-West Nigeria, to ascertain
      related factors in organizational climate that can cause dissatisfaction among
      academics; and to determine if there is a significant difference in the way
      senior academics and junior academics perceive the existing organizational
      climate. A total of 384 copies of questionnaires were administered to selected
      five (5) private Universities in the South-West Zone of Nigeria but a total of
      293 questionnaires were returned fully and appropriately filled. The study made
      use of appropriate statistics such as measurement model (Confirmatory Factor
      Analysis) and Multiple Regression to obtain results.

PMID- 30229045
TI  - Data for global power demand and solar PV output matching.
AB  - Increasing use of solar energy necessitates better data sets for analyzing
      matching of solar photovoltaic output and power demand. Data source information
      presented in this article is useful to analyze the self-consumption rates of
      photovoltaic systems on global scale. The data is provided in figure format. The
      time resolution is basically one hour, but 1-min data is also included. The
      geographical range of selected sites is lat. 26-60 deg. (Europe, Asia, Latin
      America). The power demand data ranges from a single household to national scale.
      Both measured and simulated data are included. The data sets are linked to a
      recent article by Lund [1].

PMID- 30229046
TI  - Dataset on the assessment of water quality and water quality index of Ubogo and
      Egini rivers, Udu LGA, Delta State Nigeria.
AB  - The article contains datasets built on a baseline study on the selected
      physicochemical parameters and Water Quality Index of Ubogo and Egini Rivers,
      Delta State, for a period of six months, spanning the time frame between February
      - July, 2010. Within this space, six stations were shared equally among the two
      rivers using the three communities they flow through as guide, and water samples
      were collected on monthly basis from these stations. The objectives include
      determination of the spatial variations and background concentrations of the
      selected physicochemical parameters. Sixteen physicochemical parameters were
      analyzed in the water. Current velocity, air and water temperature were
      determined in-situ; the rest physicochemical parameters were determined via
      adopting standard methods. Apart from turbidity, the values of the rest physical
      parameters - air and water temperature, TDS showed significant difference (p <
      0.05) across the stations.

PMID- 30229048
TI  - Influence of support media supplementation to reduce the inhibition of anaerobic
      digestion by phenol and ammonia: Effect on degradation performances and microbial
      dynamics.
AB  - Data in this article provide detailed information on the microbial dynamics
      within digesters supplemented with different support media (two types of
      zeolites, two types of activated carbons, one type of chitosan, one control) in
      presence of different inhibitory conditions (control without inhibitor, 1.3 g/L
      of phenol and 19 g/L of total ammonia nitrogen). Data include the operational
      conditions and degradation performance measurements, as well as microbial
      community analysis, by 16S rRNA gene sequencing, at different time points for the
      different conditions (samples). Sequencing data were generated by using
      IonTorrent PGM sequencer. This data is associated with the research articles
      "Improving anaerobic digestion with support media: Mitigation of ammonia
      inhibition and effect on microbial communities?" (Poirier et al., 2017) [1] and
      "Support media can steer methanogenesis in presence of phenol through biotic and
      abiotic effects" (Poirier et al., 2018) [2]. The sequencing data have been
      deposited with links to BioProject accession number PRJNA450513, in the NCBI
      BioProject database (https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA450513). Samples
      accession numbers go from SAMN08940368 to SAMN08940426.

PMID- 30229047
TI  - Draft genome sequence of Pantoea ananatis strain MHSD5 isolated from surface
      sterilized leaves of medicinal plant, Pellaea calomelanos obtained in South
      Africa.
AB  - Pantoea ananatis strain MHSD5 is a bacterial endophyte isolated from the surface
      sterilized leaves of Pellaea calomelanos, which is a medicinal plant obtained in
      Limpopo province of South Africa. We present here the draft genome sequence and
      annotation of P. ananatis strain MHSD5. The genome assembly was 4.6 Mb in size
      with an N50 of 550,557 bp. A total of 4,350 putative protein coding sequence
      genes were predicted with PGAAP. This is the first draft genome of a bacterial
      endophyte symbiotically associated with P. calomelanos. This Whole Genome Shotgun
      project has been deposited at DDBJ/ENA/GenBank under the accession PUEK00000000.
      The version described in this paper is version PUEK01000000.

PMID- 30229049
TI  - Complete host specificity test plant list and associated data to assess host
      specificity of Archanara geminipuncta and Archanara neurica, two potential
      biocontrol agents for invasive Phragmites australis in North America.
AB  - Introduced European genotypes of Phragmites australis are invasive and widespread
      in North America. Decades of management using herbicide and other means have
      failed to control the species and its range and populations continue to expand.
      Allowing continued invasion threatens native wetland biota and an endemic North
      American subspecies Phragmites australis americanus. The lack of conventional
      management to control introduced P. australis triggered research to assess host
      specificity of two European noctuid moths, Archanara geminipuncta and Archanara
      neurica. These two species are considered particularly promising potential
      biocontrol agents for introduced P. australis. Here we provide the complete and
      approved list of test plants used to assess host specificity of A. geminipuncta
      and A. neurica. This includes data on neonate larval acceptance and survival
      under no-choice conditions, and oviposition tests for all plant species tested,
      including for different Phragmites subspecies currently occurring in North
      America. We further provide temperature profiles of select cities in the
      temperate native European distribution of the two noctuids and those in southern
      US climates. We used these long-term temperature records to assess whether
      overwintering eggs of A. geminipuncta and A. neurica can survive under climate
      conditions typical for the Gulf Coast region in North America. This data article
      refers to "Host specificity and risk assessment of Archanarageminipuncta and
      Archanaraneurica, two potential biocontrol agents for invasive
      Phragmitesaustralis in North America Biol. Control (2018)".

PMID- 30229050
TI  - Data maps and method for evaluating the indicator of the risk of propagation of
      invasive exotic plant species on work zones.
AB  - Invasive exotic plant species are considered a serious threat to plant diversity.
      Creating work zones involves actions that disturb balances existing among species
      in the ecosystems and thus promote the propagation and the development of
      invasive plants. In this context, the Gaz Reseau Distribution France "GRDF", the
      major french natural gas distributor, with the support of the French National
      Museum of Natural History "MNHN" and the Research center focused on innovation in
      gas and new energy sources ENGIE Lab CRIGEN, sought to develop a method for
      evaluating the risk of propagation of invasive alien plant species in GRDF work
      zones. When these kind of species are identified, in a woks zone the method
      calculates the risk of propagation, and depending on the case, specific actions
      can be recommended. The aim of this paper is to provide data maps and to explain
      the method developed for the calculation of the risk of propagation of invasive
      alien plant species in work zones.

PMID- 30229051
TI  - Items parameters of the space-relations subtest using item response theory.
AB  - This article describes the item parameters analysis result of the space-relations
      subtest measurement. This subtest is part of the differential aptitude test (DAT)
      instrument. The item parameters are characteristic psychometric refer quality of
      the item. The Item parameters than analyzed in this instrument are item fit
      model, item difficulty, item discrimination, pseudo-guessing, item information
      curves, and test information function. The data was collected through
      documentation technique from the space-relation test conducted at Biro Psikologi
      (Psychology Bureau) UNY, amounting to 1046 students from Yogyakarta, Indonesia.
      Data were analyzed using item response analysis with the assistance of BILOG
      program.

PMID- 30229052
TI  - The data on the removal of turbidity and biological agents in spent filter
      backwash by bed ceramic in water treatment process.
AB  - The use of a ceramic membrane is not only a new and modern technique, but reduce
      the use of chemicals and coagulants as well, and also having high mechanical and
      chemical resistance reduces costs over consecutive years. The aim of this
      research was to remove turbidity and biological agents such as Diatoms,
      Chlorophyte, Cyanophyceae, Protozoa, and Nematodes by using of ceramic membranes.
      A ceramic pilot plant was designed and constructed. Titanium oxide (TiO2) and
      aluminum oxide (Al2O3) ultrafiltration membrane with the length, diameter and
      pore sizes of 25 cm, 2.7 cm, and 50 nm was used. The inlet flow was the effluent
      resulted from the backwashing of a sand filter. This data showed that the
      possibility of removing of this agent was high by comparing the size of the
      agents and ceramic membrane pore size. Therefore, the construction of a pilot
      plant of ceramic membranes with 50 nm pore size and dimension (H = 1.5 m, Y = 20
      cm, X = 50 cm) was offered a constant flow filtration, and sampling was performed
      at different times. The results showed that all biological agents except diatoms
      have a removal efficiency of 100% and the effluent's turbidity was 0.1 NTU.

PMID- 30229053
TI  - Impact of cardiovascular and immunologic variables on subclinical carotid
      atherosclerosis in subjects with anti-phospholipid antibodies.
AB  - Whereas some previous data on carriers with isolated antiphospholipid antibodies
      positivity (APP) suggested an increased risk of arterial events in this clinical
      setting, no data are available on subclinical atherosclerosis in this clinical
      setting. This article reports data on intima-media thickness of the common
      carotid artery (CCA-IMT) and of the Bulb (Bulb-IMT) and on the prevalence of
      carotid plaques in APP carriers and in subjects with antiphospholipid syndrome
      (APS) specifically stratifying for the presence of thrombotic manifestations,
      cardiovascular risk factors, antibody isotype and concomitant Systemic Lupus
      Erythematosus (SLE) or other autoimmune diseases.

PMID- 30229054
TI  - Experimental dataset of enhanced rheological properties and lubricity of Nigerian
      bentonite mud using kelzan(r) xcd polymer and identifying it optimal combination.
AB  - The experimental dataset in this article are for improved rheological properties
      and lubricity of Nigerian bentonite mud using Kelzan(r) xcd polymer and
      identifying it optimal combination. For this study, water base mud was formulated
      using a Nigerian bentonite and a statistical based method was used to analyze the
      rheological and lubricity properties of the drilling fluid, when enhanced with
      kelzan(r) xcd polymer. The significant and interaction level of these factors
      were closely observed on the mud properties test that were conducted. The use of
      response surface design was engaged to analyze the influence of bentonite
      quantity and the quantity of kelzan(r) xcd polymer on the lubricity and
      rheological properties of the mud. Minitab 17 (Minitab Inc. USA) was used for the
      response surface design. The p-values were used to determine which of the factors
      in the model are statistically significant, which was compared to alpha-level
      (0.05). The p-values for the quantity of kelzan(r) xcd polymer are 0, 0, and
      0.007 for Apparent viscosity (cp), Yield point (Ib/100 ft^2), Plastic viscosity
      (cp) respectively. All these values are lesser than the alpha-level (0.05), which
      means that the effect of kelzan(r) xcd polymer is significant on the model. While
      the effect of Bentonite content and the interaction between Bentonite content and
      kelzan(r) xcd polymer are insignificant because their p-values are higher than
      the -level (0.05).

PMID- 30229055
TI  - Experimental data of the study on H-rotor with semi-elliptic shaped bladed
      vertical axis wind turbine.
AB  - The performance and load test data of the proposed H-rotor with semi-elliptical
      shaped blade vertical axis wind turbine is carried out at the laboratory using 1
      m diameter axial fan. India has a long coastline and low-wind velocity ranging
      from 3 to 10 m/s which is available everywhere in the country irrespective of
      climatic conditions. The data article is carried out at different aspect ratios
      along with tilt of the blades and without tilting of the blades. These data sets
      provide the researchers to further study experimentally as well as numerically in
      order to enhance the performance of the proposed VAWT. The data presented here
      are measured at wind velocity ranging from 3 to 6 m/s. The raw data captured
      using data acquisition system are processed and presented in a form so as to
      compare it with other typical VAWT.

PMID- 30229057
TI  - R program for estimation of group efficiency and finding its gradient. Stochastic
      data envelopment analysis with a perfect object approach.
AB  - The data presented here are related to the research article "Energy-environmental
      efficiency and optimal restructuring of the global economy" (Vaninsky, 2018) [1].
      This article describes how the world economy can be restructured to become more
      energy-environmental efficient, while still increasing its growth potential. It
      demonstrates how available energy-environmental and economic information may
      support policy-making decisions on the atmosphere preservation and climate change
      prevention. This Data article presents a computer program in R language together
      with examples of input and output files that serve as a means of implementation
      of the novel approach suggested in publication [1]. The computer program utilizes
      stochastic data envelopment analysis with a perfect object (SDAEA PO) to
      calculate the group efficiency of a collection of decision-making units (DMUs),
      the efficiency gradient, and the projected gradient. The projected gradient is
      computed in the case when the SDEA PO inputs and outputs are given as shares in
      total, to satisfy the constraints of adding up to a unit. By so doing, the
      program assesses the energy-environmental efficiency of the global economy and
      determines the ways of its maximum possible increase via locally optimal economic
      restructuring.

PMID- 30229056
TI  - Data on effluent toxicity and physicochemical parameters of municipal wastewater
      treatment plant using Daphnia Magna.
AB  - Toxicity of Municipal Wastewater Treatment Plant Effluent (MWWTPE) was evaluated
      using bioassay with Daphnia Magna (D. Magna). Acute toxicity tests were performed
      on effluent samples of Urmia municipal wastewater treatment plant (Biolac system)
      according to the USEPA methods and 24, 48, 72, and 96 hr lethal concentration 50%
      (LC50) were calculated by application of Probit analysis. Also interrelationship
      between main effluent physicochemical parameters of wastewater (BOD5, COD, and
      TSS) and 24hr-LC50, were studied. Results showed that the effluent was safe to be
      discharged to the surface water in regard to physicochemical parameters and acute
      toxicity unit (TUa), according to the standards of Iranian Department of
      Environment (DOE). Relationship between effluent COD and 24hr-LC50 show that,
      increase in effluent COD resulted in increase in wastewater toxicity and there
      was not relationship between BOD5, TSS and toxicity of effluent.

PMID- 30229058
TI  - Major element data, 40Ar/39Ar step-heating and step-crushing data for
      anorthoclase megacrysts from the Newer Volcanic Province, south-eastern
      Australia.
AB  - We provide the dataset associated with the research article "40Ar/39Ar ages of
      alkali feldspar xenocrysts constrain the timing of intraplate basaltic volcanism"
      Matchan et al. [1]. This dataset contains major element data for 15 large
      anorthoclase xenocrysts ('megacrysts') collected from six Pleistocene eruption
      centres (Mount Leura, Mount Shadwell, Mount Noorat, Mount Franklin, Lake
      Keilambete and The Anakies (East Cone)) in the basaltic Newer Volcanic Province
      of south-eastern Australia. It also contains multi-collector (Argus VI) 40Ar/39Ar
      step-heating for 13 of these anorthoclase megacrysts. 40Ar/39Ar vacuo step
      crushing experiment data is also provided for three of these megacrysts.

PMID- 30229059
TI  - Dataset of long term variation in species occurrence and abundance of tintinnid
      assemblages in Jiaozhou Bay, China.
AB  - This article contains supportive data related to a research article entitled
      "Annual variation of species richness and lorica oral diameter characteristics of
      tintinnids in a semi-enclosed bay of western Pacific" (Feng et al., 2018) [1].
      This article describes long term data of tintinnid assemblages in Jiaozhou Bay,
      Yellow sea, a semi-enclosed basin ecosystem of western Pacific, from May 2003 to
      December 2012. We sum up the whole dataset for each year showing tintinnid
      species occurrence and abundance at each site by date, as well as the
      photographic documentation of each tintinnid species. Further interpretation and
      discussion can be found in recently published by Feng et al. in Estuarine,
      Coastal and Shelf Science at Science.

PMID- 30229060
TI  - Quantitative and qualitative analysis of dental clinics waste in Zabol city,
      Iran.
AB  - Dental clinics are one of the sources of waste production that are important due
      to producing infectious and potentially infectious waste, chemical and
      pharmaceutical waste, and toxic waste. Therefore, this study aimed to analyze
      dental clinics in Zabol quantitatively and qualitatively. This descriptive cross
      sectional study was conducted in 2014 on waste produced in dental clinics in
      Zabol. Sampling of 25 dental clinics was performed three times per week. At the
      end of the working day, the samples were transferred to a suitable site and
      weighed carefully after separation of the components. Data were analyzed using
      descriptive statistics and Excel software. 5457 kg of waste is annually produced
      in the dental clinics of Zabol that the amount of infectious and potentially
      infectious waste, household-like waste, chemical and pharmaceutical waste, and
      toxic wastes are approximately 48.08, 43.75, 7.82 and 0.35%, respectively. Given
      that proper management of waste produced is not performed in dental clinics in
      Zabol, special attention to waste produced in this sector through programs of
      reduction in source, separation and recycling can reduce the waste volume
      significantly.

PMID- 30229061
TI  - Draft genome sequence of Taiwanese pear (Pyrus pyrifolia).
AB  - Pear (genus Pyrus) is one of the oldest temperate fruit crops, of which at least
      22 primary species are recognized. This article documents the public availability
      of the partial draft genome sequence data of the Taiwanese pear 'Hengshanli' that
      is less dormant during the winter season. This dataset may be used to prepare
      molecular markers for the breeding of new cultivars that are subjected to
      chilling at low temperatures to overcome endodormancy. This data will also help
      analyze the process of evolution in the Pyrus species. We sequenced paired-end
      libraries using Illumina HiSeq. 2500 and generated approximately 210M reads. Data
      on the draft genome obtained in this study has been deposited to the DNA Data
      Bank of Japan (DDBJ). The read data were submitted to the DDBJ Read Archive
      (BioProject: PRJDB6877, BioSample: SAMD00117052).

PMID- 30229062
TI  - Survey data on employees' perception of the impact of community development
      initiatives on the corporate image of oil and gas firms in Nigeria.
AB  - Several sources of today's pressure on managers in strategic decision-making are
      directly associated with social issues rather than traditional strategic
      management issues. It is believed that firms that invest in community development
      are more likely to operate in harmony in the society of their operations, as such
      reduce interference from their host community, thus leading to enhanced corporate
      image. Therefore, it becomes pertinent to present data to show the existence or
      otherwise of a relationship between community development initiatives and the
      firm's corporate image. This data is gotten from 336 respondents from four top
      oil and gas firms quoted in the Nigerian stock exchange. Responses wee gathered
      from the employees' of the firms, as it is believed they have first hand
      information on the firm's corporate social responsibility policies. The data is
      purely descriptive and was gotten through quantitative methods, specifically
      through a survey questionnaire. The questionnaire had two sections; section A
      contained background questions, while section B consisted of questions that were
      specific to community development initiatives and corporate image. The Cronbach
      alpha internal consistency of the questionnaire revealed a reliability
      coefficient of 0.732, thus revealing a high consistency level. The field data set
      is made widely accessible to enable critical investigation into the subject.

PMID- 30229063
TI  - Job design and behavioural outcome of employees in agricultural research
      training, Ibadan, Nigeria.
AB  - This study focused on the relationship between job design and behavioural
      outcomes of employees in Agricultural Research Training, Ibadan, Oyo State,
      Nigeria. The study was quantitative and the items in the questionnaire were
      adapted from previous studies. A total of 227 respondents were surveyed and
      statistical regression models were used to examine the relationship between the
      independent variables (job design) and dependent variables (employee behavioural
      outcomes). The findings showed that 14.4% of the variance in job design
      dimensions can explain the variance in employee behavioural outcome. The model
      revealed that task identity, sense of autonomy and skill variety had more
      statistical significance in predicting employee behavioural outcome, recording
      the highest beta value than other variables such as task significance and
      feedback mechanisms. The model indicates that the strength of regression weights
      of paths has a strong direction.

PMID- 30229064
TI  - Survey data on users perception of flexibility of spaces in selected cultural
      center in southwest Nigeria.
AB  - Architects that specialize in designing cultural centers have often been accused
      of providing spaces that become obsolete in the coming years. This is because as
      technology and time changes, requirements also change, necessitating new
      arrangement of spaces. Very few of the spaces provided in cultural centers can
      however be adapted to other uses. This has affected the sustainability of those
      spaces. These data present the perceptions of users on the need for, and the
      features that enhance flexibility in cultural centers. The data were obtained
      from a questionnaire survey of users of the three (3) cultural centers in
      Nigeria. The survey was conducted between October and November 2017. The data may
      facilitate the evidence-based approaches to facilitate improved built environment
      and will be useful to built environment professionals, policy makers and design
      researchers.

PMID- 30229065
TI  - Dataset for regulation between lncRNAs and their nearby protein-coding genes in
      human cancers.
AB  - This article contains data related to the research article entitled "Systematic
      analysis reveals long noncoding RNAs regulating neighboring transcription factors
      in human cancers" (Liu et al., 2018 in press) [1]. Long noncoding RNAs (lncRNAs)
      are proposed to play essential roles in modulating the expression of the nearby
      loci. In this study, we systematically investigated the relationship between
      lncRNAs and their neighboring genes based on the genomic location of genes and
      the transcriptome expression profiles from TCGA samples across 12 tumor types.
      Position conservation analysis was applied to find lncRNAs conserved by position
      across vertebrate species. Gene ontology and enrichment analysis identified TF
      genes as a specific type of protein-coding genes that adjacent to highly
      positionally conserved lncRNA. The expression correlation of lncRNAs and their
      adjacent TFs were assessed across tumors to define significant co-expressed
      lncRNA-TF pairs, and a causal inference test (CIT) was used to infer the causal
      regulation of lncRNA on its nearby TF genes. A list of candidate lncRNA/TF
      regulation pairs in tumors was provided.

PMID- 30229066
TI  - datasets on employee value proposition (evp) and performance of selected fast
      moving consumer goods (FMCGs) firms in Nigeria.
AB  - The article presented an integrated dataset on employee value proposition (EVP)
      and performance of selected Fast Moving Consumer Goods (FMCGs) firms in Nigeria.
      The study adopted quantitative approach with a descriptive research design to
      establish the major determinants of employee value proposition. The population of
      this study included staff and management of the selected firms. Data was analysed
      with the use of measurement and structural equation modelling and the field data
      set is made widely accessible to enable critical or a more comprehensive
      investigation. The findings identified career growth and reward flexibility as
      predictive determinants of EVP for increased performance of sampled firms. It was
      recommended that FCMGs firms need to adopt consistent range of strategies to
      improve company strength and ethical culture for performance to be heightened.

PMID- 30229067
TI  - Data set on the experimental investigations of a helical Savonius style VAWT with
      and without end plates.
AB  - The performance test on a helical Savonius style VAWT are carried out with end
      plates and without end plates for low wind velocities from 3 m/s to 6 m/s. The
      raw data measured using instruments are recorded using digital acquisition
      system. These data are processed and presented as dimensionless parameters
      namely, coefficient of power, coefficient of torque and tip speed ratio in order
      to compare it with other VAWTs.

PMID- 30229068
TI  - The assembled transcriptome of the adult horn fly, Haematobia irritans.
AB  - The horn fly, Haematobia irritans irritans (Linnaeus, 1758; Diptera: Muscidae), a
      hematophagous external parasite of cattle, causes considerable economic losses to
      the livestock industry worldwide. This pest is mainly controlled with
      insecticides; however, horn fly populations from several countries have developed
      resistance to many of the products available for their control. In an attempt to
      better understand the adult horn fly and the development of resistance in natural
      populations, we used an Illumina paired-end read HiSeq and GAII approach to
      determine the transcriptomes of untreated control adult females, untreated
      control adult males, permethrin-treated surviving adult males and permethrin +
      piperonyl butoxide-treated killed adult males from a Louisiana population of horn
      flies with a moderate level of pyrethroid resistance. A total of 128,769,829,
      127,276,458, 67,653,920, and 64,270,124 quality-filtered Illumina reads were
      obtained for untreated control adult females, untreated control adult males,
      permethrin-treated surviving adult males and permethrin + piperonyl butoxide
      treated killed adult males, respectively. The de novo assemblies using CLC
      Genomics Workbench 8.0.1 yielded 15,699, 11,961, 2672, 7278 contigs (>= 200 nt)
      for untreated control adult females, untreated control adult males, permethrin
      treated surviving adult males and permethrin + piperonyl butoxide-treated killed
      adult males, respectively. More than 56% of the assembled contigs of each data
      set had significant hits in the BlastX (UniProtKB/Swiss-Prot database) (E
      <0.001). The number of contigs in each data set with InterProScan, GO mapping,
      Enzyme codes and KEGG pathway annotations were: Untreated Control Adult Females -
      10,331, 8770, 2963, 2183; Untreated control adult males - 8392, 7056, 2449, 1765;
      Permethrin-treated surviving adult males - 1992, 1609, 641, 495; Permethrin + PBO
      treated killed adult males - 5561, 4463, 1628, 1211.

PMID- 30229069
TI  - Impact of precursor concentration on biological synthesis of cobalt oxide
      nanoparticles.
AB  - The data provided in the article is in association with the journal article
      "Synthesis of cobalt oxide nanoparticles using endophytic fungus Aspergillus
      nidulans". Characterization data (ultraviolet-visible (UV-vis) spectroscopy,
      dynamic light scattering (DLS) analysis, scanning electron microscopy (SEM),
      field emission gun scanning electron microscopy (FEGSEM)) of nanoparticles
      synthesized using different precursor concentrations (2 mM and 10 mM) have been
      presented in this article. Data obtained by t-test and F-test have been given for
      absorbance values exhibited by nanoparticles synthesized using different
      concentrations. Required figures and table have been depicted.

PMID- 30229070
TI  - Dataset on humanic clues and customer loyalty in selected hospitals in Lagos
      State, Nigeria.
AB  - This article describes survey result on humanic clues and customer loyalty in
      selected hospitals in Lagos State, Nigeria. This paper obtains information from
      the customer experience management strategy in considering the techniques in
      which customer loyalty can be built. 365 copies of questionnaires were retrieved
      from the customers of the selected four private hospitals in Lagos State. The
      data gathered from the survey customers were subjected to inferential and
      descriptive statistics in order to ascertain the sum, mean, standard deviation
      and the relative importance index (RII). The retrieved copies of questionnaires
      were analysed utilising SPSS (22). Using the Categorical Regression CATREG
      analysis, the data article establish that humanic clues have positive influence
      on customer loyalty. The data collected is openly presented to enhance further
      analysis.

PMID- 30229071
TI  - Data on network of live cattle exports from Brazil.
AB  - This report describes the network of live cattle exports from Brazil using
      Microsoft Office Excel(r) files, Terraview(r), Maporama(r), Pajek(r) and Google
      Maps(r) softwares. The database contains estimates obtained from the Ministry of
      Agriculture, Livestock and Food Supply (MAPA) and underwent descriptive, spatial
      and flow network. The network of live cattle exports from Brazil was determined
      using data from 27,517 Animal Transit Certificates (ATC) and 579 Veterinary
      Certificate for International Trade. International departure points,
      municipalities and states of origin, destination countries, purpose of export and
      compliance with sanitary requirements for exports, cattle movement and the main
      transportation corridors were showed through flow network. The states that
      exported live cattle were Para, Rio Grande do Sul, Tocantins, Sao Paulo, Minas
      Gerais and Maranhao. Vila do Conde Port, located in Barcarena municipality in the
      state of Para, was the main international departure point of animals, which were
      intended mostly for immediate slaughter in the importing country. The internal
      cattle transportation corridors of the main counties and farms that provide
      animals for exports in 2009 were mapped.

PMID- 30229072
TI  - An open-access dataset of crop production by farm size from agricultural censuses
      and surveys.
AB  - This dataset is a cross-country convenience sample of primary data measuring crop
      production and/or area by farm size for 55 countries that underlies the article
      entitled "How much of the world's food do smallholders produce?" (DOI:
      https://doi.org/10.1016/j.gfs.2018.05.002). The harmonized dataset is nationally
      representative with subnational resolution, sourced from agricultural censuses
      and household surveys. The dataset covers 154 crop species and 11 farm size
      classes, and is ontologically interoperable with other global agricultural
      datasets, such as the Food and Agricultural Organization's statistical database
      (FAOSTAT), and the World Census of Agriculture (WCA). The dataset includes
      estimates of the quantity of food, feed, processed agricultural commodities,
      seed, waste (post-harvest loss), or other uses; and potential human nutrition
      (i.e., kilocalories, fats, and proteins) generated by each farm size class. We
      explain the details of the dataset, the inclusion criteria used to assess each
      data source, the data harmonization procedures, and the spatial coverage. We
      detail assumptions underlying the construction of this dataset, including the use
      of aggregate field size as a proxy for farm size in some cases, and crop species
      omission biases resulting from converting local species names to harmonized
      names. We also provide bias estimates for commonly used methods for estimating
      food production by farm size: use of constant yields across farm size classes
      when crop production is not available, and relying on nationally representative
      household sample surveys that omitted non-family farms. Together this dataset
      represents the most complete empirically grounded estimate of how much food and
      nutrition smallholder farmers produce from crops.

PMID- 30229073
TI  - Dataset on photodegradation of tetracycline antibiotic with zinc stannate
      nanoflower in aqueous solution - Application of response surface methodology.
AB  - Removal of pharmaceutical ingredients such as tetracycline from aqueous solution
      has a great importance. The aim of the current study was to investigate the
      degradation of tetracycline antibiotic in the presence of a triode semiconductor
      oxide as well as modeling of the photocatalytic degradation process in order to
      determine optimal condition Zinc stannate nanoflower (Zn2SnO4) was synthesized by
      hydrothermal process and characterized by X-ray diffraction (XRD), Fourier
      transform infrared (FT-IR), and scanning electron microscopy (SEM) techniques.
      Response surface methodology (RSM) was used to model and optimize four key
      independent variables, including photocatalyst dosage, initial concentration of
      tetracycline antibiotic (TC) as model pollutant, pH and reaction time of
      photocatalytic degradation. The proposed quadratic model was in accordance with
      the experimental results with a correlation coefficient of 98%. The obtained
      optimal experimental conditions for the photodegradation process were the
      following: zinc stannate (ZTO) dosage=300 mg L-1, initial concentration of TC= 10
      mg L-1, reaction time= 100 min and pH=4.5. Under the optimal conditions, the
      predicted degradation efficiency was 95.45% determined by the proposed model. In
      order to evaluate the accuracy of the optimization procedure, the confirmatory
      experiment was carried out under the optimal conditions and the degradation
      efficiency of 93.54% was observed, which closely agreed with the predicted value.

PMID- 30229074
TI  - A geospatial database of drought occurrence in inland valleys in Mali, Burkina
      Faso and Nigeria.
AB  - The data described in this article are related to drought occurrence in inland
      valleys and farmers adaptation strategies. The data were collected in 300 inland
      valleys distributed in 14 regions of West Africa. The data were collected in two
      phases. In the first phase, 300 inland valleys were identified in 14 regions and
      their locations were determined with handheld GPS devices. Questionnaires and
      informal interviews were administered to inland valleys users to collect data on
      physical and socio-economic characteristics, hydrology, farmers experience with
      drought affecting rice production in inland valleys and adaptation strategies. In
      the second phase, the locations of the inland valleys were imported in a GIS
      environment and were used to extract additional parameters on soil
      characteristics and water demand from the Shuttle Radar Topography Mission
      (SRTM), Africa Soil Information Service (africasoils.net) and POWER database
      (http://power.larc.nasa.gov). In total, the dataset contains 41 variables divided
      into seven themes: farmers' experience with drought, adaptive management of rice
      farmers to drought, physical characteristics, hydrology, management practices,
      socio-economic characteristics and weather data of inland valleys.

PMID- 30229075
TI  - Survey dataset on the performance of combined process of coagulation and ceramic
      membrane for the removal of reactive black19.
AB  - The aim of data article was to evaluate effectiveness of the combined process of
      coagulation, flocculation and filtration to remove reactive black 19 from
      solution aqueous. In this data article, alum and ferric chloride were selected as
      a coagulant for instability of color before ceramic membrane. All experiments
      were performed in batch conditions. The results showed that more than half of the
      ceramic membrane is made of silica. The BET surface area of the ceramic membrane
      was 1.877 m2 g-1. The size of RB19, alum, and ferric chloride was 996.2 mm, 1216
      mm, and 86.26 mm, respectively. Also, the zeta potential of RB19, alum, and
      ferric chloride was 20.7 mV, 1.59 mV, and 34.7 mV, respectively. The findings
      showed that the best pH to remove the RB 19 by alum and ferric chloride was less
      than 7. With increasing concentrations of alum and chlorine ferric the removal of
      RB 19 increased. For RB19 concentration of 10 mg l-1, with increasing time from 5
      to 15 min, the removal efficiency for alum and ferric were 61-63% and 82-87%,
      respectively.

PMID- 30229076
TI  - Differential expression of olive flounder (Paralichthys olivaceus) transcriptome
      during viral hemorrhagic septicemia virus (VHSV) infection at warmer and colder
      temperature.
AB  - The data presented here are related to the research article entitled "Temperature
      dependent immune response of olive flounder (Paralichthys olivaceus) infected
      with viral hemorrhagic septicemia virus (VHSV)" [1]. In the cited article, we
      sequenced the whole transcriptome of the olive flounder using Illumina RNA-Seq.
      Differentially expressed genes (DEG) analysis of VHSV infected head kidney
      samples showed perturbations in gene expression. Herein we made a comparison of
      DEGs at early stage of VHSV infection of olive flounder (4 h post infection) in
      colder (13  degrees C) and warmer (20  degrees C) temperatures. The analysis of
      signaling pathways showed that several major immune pathways were altered. The
      gene ontology terms associated with the genes differentially expressed are also
      presented.

PMID- 30229077
TI  - A dataset of synthetic face centered cubic 3D polycrystalline microstructures,
      grain-wise microstructural descriptors and grain averaged stress fields under
      uniaxial tensile deformation.
AB  - This data article presents a data set comprised of 36 synthetic 3D equiaxed
      polycrystalline microstructures, the microstructural descriptors for each grain,
      and the stress and strain fields resulting from crystal plasticity simulations
      mimicking uniaxial tensile deformation to a total strain of 4%. This is related
      to the research article entitled "Applied Machine Learning to predict stress
      hotspots I: Face Centered Cubic Materials" (Mangal and Holm, 2018) [1]. The
      microstructures were created using an open source Dream.3D software tool, and the
      crystal plasticity simulations were carried out using the elasto-viscoplastic
      fast Fourier transform (EVPFFT) method. Six different kinds of FCC textures are
      represented with six stochastically different microstructures with varying
      texture intensity for each texture kind. This dataset is freely available in a
      Mendeley Data archive "A dataset of synthetic face centered cubic 3D
      polycrystalline microstructures, grain-wise microstructural descriptors and grain
      averaged stress fields under uniaxial tensile deformation" located at
      <http://dx.doi.org/10.17632/ss75fdg5dg.1> for any academic, educational, or
      research purposes.

PMID- 30229078
TI  - Feta cheese proteins: Manifesting the identity of Greece's National Treasure.
AB  - Over the last years, there has been tremendous debate regarding the identity of
      feta cheese and under which terms such food with historical ties to ancient
      Greece can be discriminated among others, based on its unique traits and
      characteristics. This analysis sets the foundation towards a much anticipated
      control procedure, by deciphering for the first time the core elements of this
      food; its proteins. In this initial report, we amassed representative feta cheese
      samples/types from parts of Greece entitled to produce this "protected
      designation of origin" (p.d.o) cheese type and analyzed in full their protein
      content by employing exhaustive deep-proteome analyses. Several groups of
      proteins were identified, implicated in diverse functions as well as proteins
      under multiple abundances, while the final feta cheese protein list was set to
      include solely core-proteins identified in every analyzed sample. Through this
      data article we report, for the first time, the complete protein content of feta
      cheese, consisting of 489 proteins, thus setting the foundation towards
      developing a method for identification of the original Greek product.

PMID- 30229079
TI  - Efficiency of sequencing batch reactor for removal of organic matter in the
      effluent of petroleum wastewater.
AB  - The main aim of this research was to study the biodegradation of Methyl Tertiary
      Butyl Ether (MTBE) using aerobic sequencing batch reactor (SBR) at a pilot-Scale.
      The reactor was made of a 3 mm-thick glass cylinder with an internal diameter of
      12 cm and height of 60 cm. SBR operated in five phases. The first phase was
      filling the reactor for about 10 min. the second phase was the main reactor for
      biological treatment of petroleum wastewater about 21.55 h. The third phase was
      the sedimentation (1 h). The fourth phase was decanting from the reactor for
      about 10 min. The last phase consisted of idle for about 45 min. The experiments
      showed that the mixed microbial mass is able to degrade high concentration of
      methanol up to 250 mg/l, and concentration of MTBE up to 70 mg/l for a 24 h
      cycle. However, the mixed microbial mass is not able to degrade MTBE with
      concentration more than 70 mg/l. Microorganisms were generally isolated from Fajr
      petrochemical wastewater treatment plant. Analysis showed that the mixed
      microbial mass able to biodegradation of COD up to 1350 mg/l in effluent. Aerobic
      SBR can be used for biological treatment of the petroleum wastewater containing
      pollutants such as methanol, MTBE with a promising efficiency.

PMID- 30229081
TI  - In situ XPS data for the uranyl-modified oxides under visible light.
AB  - The silica, alumina, ceria, and titania supports were modified with uranyl ions
      (5 wt%) and investigated using X-ray photoelectron spectroscopy. The data show
      the U4f photoelectron spectra and charge state of uranium for uranyl ions
      deposited on different supports. The additional in situ XPS experiments with
      simultaneous irradiation of the sample using a 450 nm light-emitting diode were
      performed, and the XPS spectra, revealing a partial reduction of uranium under
      visible irradiation, are presented. The data show the effect of support material
      on the chemical states of uranium and oxygen on the surface of uranyl-modified
      oxides under visible light.

PMID- 30229080
TI  - HPLC-ESI-MS method for C60 fullerene mitochondrial content quantification.
AB  - The presented dataset describes the quantification of carbon nanoparticle C60
      fullerene accumulated in mitochondria of human leukemic cells treated with
      nanostructure. Firstly, the high performance liquid chromatography-electro spray
      ionization-mass spectrometry (HPLC-ESI-MS) method was developed for quantitative
      analysis of pristine C60 fullerene. Then, human leukemic cells were incubated
      with C60 fullerene, homogenized and subjected to the differential centrifugation
      to retrieve mitochondrial fraction. The C60 fullerene content was quantified by
      HPLC-ESI-MS in extracts of cellular fractions. This data article refers to the
      research article "C60 Fullerene Accumulation in Human Leukemic Cells and
      Perspectives of LED-mediated Photodynamic Therapy" by Grebinyk et al. [1].

PMID- 30229082
TI  - Dataset on the cyclic experimental behavior of Steel frames with Reinforced
      Concrete infill Walls.
AB  - This paper presents the experimental data on the cyclic behavior of Steel frames
      with Reinforced Concrete infill Walls (SRCW). Two specimens, characterized by a
      different shear studs distribution, have been tested: the first one is provided
      with shear studs positioned only in the four corners of the steel frame; the
      second one presents shear studs all distributed along the perimeter of the steel
      frame except for the zone of the dissipative fuses. The overall setup, loading
      protocol, collapse mechanisms, force-displacement curves for both the whole
      system and the main single components are described for the two tested
      prototypes.

PMID- 30229083
TI  - Survey datasets on categories of factors militating against safety practices on
      construction sites.
AB  - The causes of occupational accidents have been classified into unsafe conditions
      and unsafe behaviour. Interestingly, numerous authors have contributed to the
      issues of safety practices in managing building production process with different
      views on factors causing construction accident and insensitiveness to safety
      practices, but there have been a little efforts to bring together major causes
      and factors militating against safety practices in unified manners. Therefore,
      all identified forty nine factors from literature review [1], [2], [3], [4], [5],
      [6], [7], [8], [9], [9], [11], [12], [13], [14], [15], [16], [17], [18], [19],
      [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32] were
      brought together and grouped into five different categories. Descriptive
      statistics were performed on the data to rank these factors as affected workmen
      on construction sites. The results were presented in figures, text file and
      tables using Mean Score. The data presented in this study were enable
      construction managers to standardize project risks assessment and management.

PMID- 30229084
TI  - Data on major power outage events in the continental U.S.
AB  - This paper presents the data that is used in the article entitled "A Multi-Hazard
      Approach to Assess Severe Weather-Induced Major Power Outage Risks in the U.S."
      (Mukherjee et al., 2018) [1]. The data described in this article pertains to the
      major outages witnessed by different states in the continental U.S. during
      January 2000-July 2016. As defined by the Department of Energy, the major outages
      refer to those that impacted atleast 50,000 customers or caused an unplanned firm
      load loss of atleast 300 MW. Besides major outage data, this article also
      presents data on geographical location of the outages, date and time of the
      outages, regional climatic information, land-use characteristics, electricity
      consumption patterns and economic characteristics of the states affected by the
      outages. This dataset can be used to identify and analyze the historical trends
      and patterns of the major outages and identify and assess the risk predictors
      associated with sustained power outages in the continental U.S. as described in
      Mukherjee et al. [1].

PMID- 30229085
TI  - Dataset on the knowledge, attitudes and practices of university students towards
      antibiotics.
AB  - Antibiotic resistance is a major public health issue globally fuelled largely by
      its misuse. Controlling this problem would require an understanding of the levels
      of awareness of the population towards antibiotics. The data presented here was
      obtained from undergraduate students attending a Nigerian University in the first
      three months of the year 2016. The data is stratified by such demographic
      variables as age, sex and level of study. It contains information about the
      knowledge, and predispositions of participants to antibiotics and antibiotic
      resistance. Preliminary descriptive statistics are presented in the tables and
      figures herewith. Data was analysed using SPSS-20 and is available for reuse in
      the native SPSS format. In concluding, this data can be used to model the
      determinants of antibiotic knowledge among students.

PMID- 30229086
TI  - Survey datasets on patterns of utilization of mental healthcare services among
      people living with mental illness.
AB  - The data was obtained from a field survey aimed at measuring the patterns of
      utilization of mental healthcare services among people living with mental
      illness. The data was collected using a standardized and structured questionnaire
      from People Living with Mental Illness (PLMI) receiving treatment and the care
      givers of People Living with Mental Illness. Three psychiatric hospitals in Ogun
      state, Nigeria were the population from which the samples were taken. Chi-square
      test of independence and correspondence analysis were used to present the data in
      analyzed form.

PMID- 30229087
TI  - Data on prevalence of additive colors in local food and beverage products,
      Tehran, Iran.
AB  - The quality check and determination of permitted and non-permitted additive
      colors in food products is very important for customer's right protection and
      health. This survey was undertaken to demonstrate the frequently use of additive
      colors and products targeted to color adulteration in Iranian foods and
      beverages. From the 1120 of the samples, 18.86% contained artificial colors,
      11.89% contained natural colors and 69.25% of samples had no additive colors.
      Tartrazine (E102) was the only non-permitted artificial dye used in samples.
      Among products with additive colors, only 4.38% of samples failed to meet with
      national Iranian standard and 61.23% of non-compliance samples were from non
      industrial sectors and mostly were saffron and food containing saffron such as
      saffron rock candy and saffron chicken. These places and products quality are
      main the concern to solve the color adulteration in Iranian food market.

PMID- 30229089
TI  - Data on a real-time tripodal colorimetric/fluorescence sensor for multiple target
      metal ions.
AB  - Currently considerable research both in life and in environmental sciences is
      dedicated to chemosensors able to detect metals of biological interest such as
      zinc and iron or other toxic and carcinogenic, as cadmium, mercury, chromium,
      lead. Recently, a new chemosensor strategy of "single chemosensor for multiple
      metals" has emerged. For this scope, many fluorescent sensors for Cd(II) and
      Zn(II) have been designed and synthetized, as ligand systems or in polymeric
      matrices [1], [2], [3]. The data presented in this article include experimental
      data on the of a pyridyl/phenolic/benzothiazole functionalized colorimetric
      receptor (BPAP) and its selectively recognise Fe(III) and Fe(II) ions with
      visible, naked eye colour changes and fluorometric selectivity towards Zn2+ and
      Cd2+ ions in aqueous medium. This article is submitted as a companion paper to
      Caruso et al. (2018) [4].

PMID- 30229088
TI  - Datasets on factors influencing the urban environmental quality of intra-urban
      motor parks across density areas of Lagos metropolis.
AB  - This survey data examined the factors influencing commuters' perception of
      environmental quality in the selected intra-urban motor parks of Ibeju Lekki,
      Ifako Ijaiye and Ikeja local government areas, Lagos State, Nigeria. A survey of
      376 commuters was carried out. The purposive sampling technique was used for the
      survey while the sampling procedure evolved from the identification of the study
      area to the administration of questionnaire with commuters in the motor parks.
      Data were analyzed using descriptive (likert scale outputs) and inferential
      statistical techniques (factor analysis for data reduction and categorization).
      The datasets can be considered in the transport and environmental policies of
      Lagos State and Nigeria with a view to engendering a conducive environment in the
      intra-urban motor parks of Lagos State, Nigeria.

PMID- 30229091
TI  - Determination of nitrate concentration and its risk assessment in bottled water
      in Iran.
AB  - Bottled water is one of the sources of drinking water in many arid and semi-arid
      countries, including Iran. The greatest concern is the health effects of exposure
      to excessive nitrate concentrations in drinking water due to the development of
      methemoglobinemia in children. Therefore, the present study was aimed at
      determining the concentration of nitrate and its risk assessment in drinking
      water bottled in Iran. 71 different bottled water brands were identified in this
      study. The nitrate concentration in water samples was then measured using an Ion
      Chromatography No. 4110 in accordance Standard Methods for the Examination of
      Water and Wastewater. The hazard quotient (HQ) of nitrate was calculated using
      the formula based on input variables including nitrate concentration, water per
      capita, body weight and reference dose. The results showed that the concentration
      of nitrate in bottled water was in the range of 0.146-50.1 mg/L (average 10.55
      mg/L) in one of which, the concentration of nitrate was higher than the WHO
      guideline. The mean EDI values for nitrate in different groups of infants,
      children, teenagers and adults were 0.0795, 0.5633, 0.3976 and 0.3186 mg/kg,
      respectively. The mean HQ values for nitrate in different groups of infants,
      children, teenagers and adults were 0.0528, 0.3737, 0.2638 and 0.2114,
      respectively. In general, the hazard quotient (HQ>1) for the population consuming
      bottled water, appropriate strategies should be considered in order to reduce the
      concentration of nitrate in bottled water.

PMID- 30229090
TI  - Experimental data on the adsorption of Reactive Red 198 from aqueous solution
      using Fe3O4 nanoparticles: Optimization by response surface methodology with
      central composite design.
AB  - The aim of this study was to evaluate the efficiency of Fe3O4 nanoparticles for
      Reactive Red 198 adsorption. The adsorbents were characterized by SEM and XRD. In
      this dataset, the influence of Reactive Red 198 dye concentration, solution pH,
      adsorbent dosage, and contact time on Reactive Red 198 dye adsorption by Fe3O4
      nanoparticles was tested by central composite design (CCD) under response surface
      methodology (RSM). The Fe3O4 nanoparticles adsorbent was prepared by chemical co
      precipitation. The process efficiency was achieved in optimal conditions
      including pH=7, adsorbent dosage equal to 0.5 g/L, initial dye concentration of
      100 mg/L, contact time equal to 30 min, 88%. Overall, the data offer a facile
      adsorbent to remove Reactive Red 198 dye from aqueous solutions.

PMID- 30229093
TI  - Stock keeping accuracy: A data based investigation of storage tank calibration
      challenges.
AB  - In fuel dispensing and fuel haulage companies, adequate stock tracking is
      mandatory for performance and business productivity analysis. Stock monitoring is
      vital for inventory management; it is a tool that enables adequate planning in
      terms of importation requirements when stock is low and for general price
      management. The accuracy of stock inventory depends largely on the accuracy of
      the calibration data of the various storage tanks and structures deployed along
      the value chain. Mobile tanks are prone to harsh conditions due to poor road
      networks in some countries which affect tanker truck alignment and suspension
      systems, and all these affects tank calibration accuracy. This is further
      aggravated by various road impacts, and accidents that sometimes distort portions
      of the tank shape making it to lose its cylindrical profile in some sections.
      Excessive stock variations is often linked to product theft and sabotage, though
      this may be true in some instances, but at times, this variations may be as a
      result of inaccuracies in tank calibration. The dataset presented in this paper
      contains tank calibration parameters for two consecutive calibrations carried out
      on the same mobile storage tank. The statistical analysis attempts to identify
      variations between the two tank calibration dataset as an indication of potential
      stock accuracy variations.

PMID- 30229092
TI  - Removal of the metronidazole from aqueous solution by heterogeneous electro
      Fenton process using nano-Fe3O4.
AB  - Among drugs, antibiotics have a significant place due to their wide consumption
      in veterinary and human medicine to prevent and treat microbial infections. In
      spite of low amounts of antibiotics in the aquatic environments, the repeated
      incidence of antibiotics has been caused bacterial persistence and adverse
      effects on health human and aquatic life. Current article evaluated the removal
      of metronidazole (MNZ) via heterogeneous electro-Fenton (EF) process by nano
      Fe3O4. The response surface methodology (RSM) on Box-Behnken design was applied
      for modeling and optimization experimental factors such as pH, applied current,
      and catalyst load. The efficiency of the EF process was maximum (92.26%) under
      the optimal condition for MNZ removal i.e. 70 mg/L of initial MNZ concentration,
      pH of 3, 200 mA applied current, 30 min time and 3.2 kWh/m3 of energy
      consumption.

PMID- 30229094
TI  - Survey dataset on leadership styles and job satisfaction: The Perspective of
      employees of hospitality providers.
AB  - This study aimed at establishing the relationship between the dimensions of
      leadership styles and employees' job satisfaction in hospitality industry in
      Nigeria. This study was prompted by reports of high labour turnover in this
      sector of the economy (especially in the guesthouses), because of reduction in
      the satisfaction of the workforce. Cross-sectional research design which is
      quantitative in nature, was the methodology adopted for this study to assess the
      trends of relationships between the constructs. Questionnaire was used as the
      measuring instrument, and reliability and validity test for the instrument were
      established using cronbach alpha, for all the variables ranging between 71% and
      89%. The study population comprises 410 employees in the six selected functioning
      guesthouses, which also represents the study sample. Total enumeration sampling
      technique was adopted. Statistical Package for Social Sciences (SPSS) software
      package (version 22) was used for the analysis of the data. The field dataset is
      available to the public for more rigorous, extensive, critical and extended
      analysis.

PMID- 30229095
TI  - The effects of radiofrequency radiation on mice fetus weight, length and tissues.
AB  - The public concern of harmful effects of radiofrequency radiation exposure,
      especially with rapid increase in the use of wireless and telecommunication
      devices, is increasing. Some studies show fetal and developmental abnormalities
      as the result of radiofrequency radiation exposure. We aimed to investigate
      possible teratogenic effects of radiofrequency in 915 MHz on mice fetus and
      protective role of vitamin C. 21 pregnant mice were divided into 3 groups.
      Control group was in normal condition without any stressor agent. Exposure group
      was exposed to 915 MHz RFR (8 h/day for 10 days) and 0.045 uw/cm2 power density.
      The exposure plus vitamin C group received 200 mg/kg vitamin C by gavage and was
      exposed to 915 MHz RFR (8 h/day for 10 days) and 0.045 uw/cm2 power density. The
      fetus weight, C-R length were measured by digital balance and caliper. Tissues
      were assessed after staining with H & E. Our results showed significant increase
      in fetus weight and C-R length and also enlarged liver, tail deformation in mice
      fetus in exposure group. Although usage of vitamin C caused significant decrease
      in mentioned parameters. The outcome of this study confirms the effects of
      radiofrequency radiation on growth parameters such as body weight, length and
      some tissues in mice fetuses and protective effect of vitamin C. However more
      studies on non-ionization radiation in different frequencies and severity, during
      pregnancy are needed to clarify the exact mechanisms of these changes and better
      protection.

PMID- 30229096
TI  - Data relating to change in locus of control orientation of parents overtime (from
      pre-birth to 20 years later), participating in the Avon Longitudinal Study of
      Parents and Children (ALSPAC).
AB  - Locus of control (LOC) measures an individual's expectancy regarding their
      ability to affect what happens to them based on their behavior. Those with an
      internal LOC (ILOC) believe their own behavior influences what happens to them.
      Those with an external LOC (ELOC) perceive that what happens to them is beyond
      their control (i.e. determined by luck, fate, chance or powerful others) [1]. A
      vast amount of research (mainly cross-sectional) suggests that an ELOC is
      associated with many adverse personal, social, academic and health outcomes. LOC
      data were uniquely collected prenatally from over 12,000 pregnant women and their
      partners enrolled in the Avon Longitudinal Study of Parents and Children
      (ALSPAC). The LOC measure used was a shortened version of the adult version of
      the Nowicki-Strickland Internal-External locus of control scale. This was
      administered to the mothers within self-completion questionnaires at three-time
      points: during pregnancy, at 6 and at 18 years post-partum. In parallel, self
      completion questionnaires containing the same LOC questions were completed by
      their partners during pregnancy, at 6 and 20 years later. ALSPAC LOC data are
      unique in that they measured orientation over time and on a much larger sample of
      respondents than is usual. We describe the scale used, why it was chosen and how
      individual scores changed over time.

PMID- 30229097
TI  - Production forecast for niger delta oil rim synthetic reservoirs.
AB  - The data sets in this article are related to a Placket Burman (PB) design of
      experiment (DOE) made on a wider range of uncertainties such as: reservoir,
      operational and reservoir architecture parameters that affect oil rim
      productivities. The design was based on a 2 level PB-DOE to create oil rim models
      which were developed into reservoir models using the Eclipse software and
      configured under the best depletion strategy of concurrent oil and gas
      production. Approximate solutions to the models was developed to forecast oil
      production using the least square method. The Monte-Carlo simulation approach was
      used in estimating 3 production forecasts for the oil rim reservoirs. This will
      help to create a probabilistic variety of forecasts that can further be used in
      making decisions.

PMID- 30229098
TI  - Protein carbonylation detection methods: A comparison.
AB  - The data reported here are a comparison among four different methods for the
      detection of carbonylated proteins, a validated biomarker of oxidative stress.
      The reference samples were heart and kidney extracts of Guinea pigs transfused
      with hemoglobin-based oxygen carriers (Alomari et al. FRBM, [11]). We measured
      the carbonyl content of organ extracts by using i) the Levine spectrophotometric
      method, which takes advantage of the chromogenic reaction of carbonyl groups with
      2,4-dinitrophenylhydrazine (DNPH), ii) a commercially available ELISA assay based
      on an anti-DNPH antibodies, iii) a commercially available Western blot method
      based on anti-DNPH antibodies and iv) an in-gel detection approach with the
      fluorophoric reagent fluorescein-5-thiosemicarbazide. The former two methods
      measure total protein carbonylation of a sample, whereas the latter two require
      an electrophoretic separation and therefore potentially allow for the
      identification of specific carbonylated proteins.

PMID- 30229099
TI  - Draft genome sequence of Japanese pear (Pyrus pyrifolia).
AB  - The Japanese pear (Pyrus pyrifolia), a member of the family Rosaceae, is one of
      the most important fruit trees in Japan. This article documents the public
      availability of the partial draft genome sequence data of the Japanese pear
      strain TH3, which is the S1 of 'Osa-Nijisseiki' and is homozygous for the S4sm
      gene. This dataset may be used to prepare molecular markers for breeding of new
      cultivars having a crisp texture and feel. This data will also help research on
      physiological disorders affecting Japanese pear fruit. We sequenced paired-end
      libraries using Illumina HiSeq. 2500 and generated approximately 212M reads. Data
      on the draft genome obtained in this study has been deposited to the DNA Data
      Bank of Japan (DDBJ). The read data were submitted to the DDBJ Read Archive
      (BioProject: PRJDB6878, BioSample: SAMD00117051).

PMID- 30229100
TI  - Survey dataset of building user-perceptions on the condition of public secondary
      school buildings in Ogun State Nigeria.
AB  - In this data article, questionnaire was administered to public secondary school
      teachers to investigate user-perceptions of the prevailing deterioration
      condition of the school buildings, in Ogun State, Nigeria. The condition of some
      factors such as, roof, paints, floor, walls, windows, doors, electrical,
      plumbing, toilets, WC, pipes, drains were the investigated variables. The data
      presented here are the opinion of the respondents. Through this research, it was
      discovered that most of the academic building of public secondary school of our
      study area were not properly managed and poorly maintained as a result of
      insufficient fund for maintenance and lack of maintenance culture.

PMID- 30229102
TI  - Dataset in the production of composite clay-zeolite membranes made from naturally
      occurring clay minerals.
AB  - The data presented in this article are generated as part of the research article
      entitled "from a naturally occurring material (clay mineral) to the production of
      porous ceramic membranes" (Elgamouz and Tijani, 2018) [1]. This article describe
      how clays as very abundant versatile materials that have many properties not
      available in pure materials namely, silica, alumina and zirconia can be used for
      the preparation of ceramic membranes (Karaborni et al., 1996; Oun et al., 2017;
      Hollanders et al., 2016; de Oliveira Henriques et al., 2017) [2], [3], [4], [5].
      This paper presents data obtained at different stages of the fabrication of a
      clay-zeolite composite ceramic membrane made from a largely available clay from
      the central region of Morocco (Meknes). The data include the characterization of
      the clay powder using XRD, FTIR, thermogravimetric (TGA and TDA) analysis of the
      clay powder. The data of porosity, mesoporosity, specific surface area, volumes
      of the pores, volumes of mesopores, diameters of the pores using mercury
      intrusion porosimetry and adsorption desorption of nitrogen data that was
      computed from BET and BJH theories of the clay supports at different firing
      temperatures (700, 750, 800, 850 and 900  degrees C). Data obtained from
      measurement of nitrogen permeation of support alone and that of the silicalite
      membranes are also represented.

PMID- 30229101
TI  - MoO3NPs/ZIF-8 composite material prepared via RCVD for photodegradation of dyes.
AB  - Toxic wastewaters from the textile industry have made its way into rivers and
      other waterways, posing a serious health treat on both human and wildlife.
      Herein, this data set presents the potential use of MoO3 nanoparticles supported
      on ZIF-8 in the photodegradation of a cationic dye molecule. The data presented
      in this article report a concise description of experimental conditions for the
      spray-dried ZIF-8 synthesis and subsequent deposition of MoO3 nanoparticles via
      rotary chemical vapor deposition (RCVD). The photodegradation and analysis data
      reviled that the MoO3-NPs@ZIF-8 3 wt% displayed the ability of degrading
      methylene blue up to 82% and 95% after 180 and 300 min, respectively.

PMID- 30229103
TI  - The data on the dispersion modeling of traffic-related PM10 and CO emissions
      using CALINE3; A case study in Tehran, Iran.
AB  - CALINE3 model predicts the dispersion of pollutants released from roadways in the
      receptor places at a certain radius from the source. This model was used to
      evaluate the dispersion of particulate matter < 2.5 um (PM10) and carbon monoxide
      (CO) emitted from Yadegar-e-Emam Expressway (YEE) as one of the most congested
      highways in Tehran. The hourly concentrations of PM10 and CO, and the count and
      speed of vehicles were obtained from Tehran's Air Quality Control Company
      (TAQCC). Wind speed and direction, the height of mixing zone, air temperature,
      relative humidity, and stability class were acquired from IRAN Meteorological
      Organization (IRIMO). The emission factors (EF) of vehicles were acquired from
      those proposed for UK. The dispersion of PM10 and CO was predicted over the
      nearby area, and the modeled concentrations were estimated for a specific point,
      where an air quality monitoring station was working. The major portion of PM10
      and CO released by vehicles in YEE was dispersed to the east. The comparison
      between the modeled and measured concentrations revealed that CALINE3
      underestimates the concentrations of PM10 and CO by about 50%.

PMID- 30229104
TI  - Dataset on aerosol loading and deposition over Nouakchott-Mauritania.
AB  - Aerosol optical depth (AOD) is a vital parameter that determines air quality over
      a geographic enclave. In this paper, the pollution state of Nouakchott-Mauritania
      was considered. Fifteen years primary (aerosol optical depth) dataset was
      obtained from the Multi-angle Imaging Spectro-Radiometer (MISR). The secondary
      datasets were generated from the primary dataset to understand the short and long
      term effect of aerosol loading over nouakchott. The dataset is important to
      resolve the ground effect of satellite measurements.

PMID- 30229105
TI  - Data on recurrent somatic embryogenesis and in vitro micropropagation of Cnidium
      officinale Makino.
AB  - Cnidium officinale Makino, a perennial herb of the family Umbelliferae, is a well
      known medicinal plant in oriental medicine with antidiabetic, tumor metastatic,
      antiplatelet, antimicrobial and insecticidal properties. Hence, C. officinale
      does not produce seed the plant tissue culture is the viable alternative for its
      propagation. Node explant from in vitro grown C. officinale Makino was cultured
      on MS medium supplemented with plant growth regulators (PGRs) like 2,4
      Dichlorophenoxyacetic acid (2,4-D) or/and 6-Benzylaminopurine (BA). It was aimed
      to investigate the optimal concentration and combination of 2,4-D and BA for
      somatic embryogenesis in node explant of C. officinale Makino. The embryogenic
      callus was induced on node explant after four weeks in MS medium containing 1.5
      mg L-1 2,4-D and 0.5 mg L-1 BA. The translucent white, embryogenic callus was
      subcultured on the respective medium and individual well-structured somatic
      embryos were observed. Heart and cotyledon stage embryos were pictured under a
      stereomicroscope. The individual somatic embryos (SE) were transferred to MS
      medium without PGRs (MS0) and 100% germination was observed. Repeated
      subculturing of the embryogenic callus for five months resulted in recurrent
      somatic embryogenesis but with a gradual decline in number.

PMID- 30229106
TI  - Interaction analysis data of simulation gaming events using the serious game Aqua
      Republica.
AB  - The data presented in this article is related to the research article entitled
      'Serious games as a catalyst for boundary crossing, collaboration and knowledge
      co-creation in a watershed governance context' (Jean et al., In press) [1].
      Understanding the team dynamics related to serious game simulations is critical
      for understanding the potential uses and functions of these simulations for
      knowledge co-creation (Medema et al., 2016) [2]. The data was obtained from four
      independent serious game simulation events and consists of n = 40 participants.
      Participants were divided into small teams and were then recorded playing the
      serious game Aqua Republica (http://aquarepublica.com/). Interactions were
      tallied and interaction maps created using the visualization software GEPHI
      (https://gephi.org/). The interaction maps allow for a visual representation of
      the progression of interactions over the course of four subsequent phases of
      gameplay (Jordan and Henderson, 1995) [3].

PMID- 30229107
TI  - Integrated datasets on transformational leadership attributes and employee
      engagement: The moderating role of job satisfaction in the Fast Moving Consumer
      Goods (FMCG) industry.
AB  - Transformational leadership has gained a great deal of attention since its
      development through research and evaluations from James MacGregor Burns and
      Bernard Bass. But central to its development, there are still uncertainties
      regarding the attributes and interventions of transformational leadership style
      in developing nations like Nigeria. Hence, this article presented an integrated
      datasets on transformational leadership attributes, employee satisfaction and
      engagement using selected Fast Moving Consumer Goods (FMCGs) firms in Nigeria.
      The study adopted a descriptive research design to establish trends and the
      quantitative approach was employed using survey questionnaire. A sample size of
      three hundred and fifty-nine (359) staff and management of sampled firms were
      selected. Data was analysed with the use of measurement and structural equation
      modelling and the field data set is made widely accessible to enable critical or
      a more comprehensive investigation. The findings identified intellectual
      stimulation (creativity and innovation) and attributed charisma as predictive
      determinants of transformational leadership attributes for increased satisfaction
      and engagement of sampled firms. It was recommended that FCMGs firms need to
      invest necessary resources in developing strategies and interventions to identify
      differing needs, abilities, and aspirations for staff satisfaction.

PMID- 30229108
TI  - Dataset of the density, water absorption and compressive strength of lateritic
      earth moist concrete.
AB  - In this data article, the experimental data of the density, water absorption and
      compressive strength of lateritic earth moist concrete are presented. 10% and 20%
      of fine aggregate were replaced with laterite. Potable water at 0.3 water/cement
      ratio was used and ordinary Portland cement used as the binder. Concrete cubes (
      150mm*150mm*150mm ) were cured and tested at 7 days, 14 days, 21 days, 28 days
      and 56 days. The reported original data is made publicly available for ensuring
      critical or extended analyses.

PMID- 30229109
TI  - Field data on plant growth and insect damage on the noxious weed Solanum
      eleaegnifolium in an unexplored native range.
AB  - In this data article, we provide a novel data set on plant growth, insect damage
      levels, and herbivore community of the noxious and invasive weed Solanum
      eleaegnifolium (Solanaceae). The data is collected from disturbed and un
      disturbed urban populations of the species from one of its unexplored native
      range in Southern United States (South Texas). The data include plant height
      measurements, insect damage levels, GPS coordinates of the populations, and their
      disturbance status. Additional data includes the number of chewing herbivore
      (specialist herbivore Texas potato beetle (Leptinotarsa texana; Chrysomelidae),
      their eggs, and any lepidopteran caterpillars found on the plants.

PMID- 30229110
TI  - Data on Legionella prevalence and water quality in showers of retirement homes
      and group homes in the Province of Rome, Lazio Region, Italy.
AB  - The data presented in this article are related to the research paper titled
      "Prevalence of Legionella in retirement homes and group homes water distribution
      systems" (De Filippis, 2018) [3]. Most of the cases of Legionella infection are
      sporadic and occur in community-dwellers. Hot water and biofilm samples from the
      showerheads of 26 retirement homes and 9 group homes hosting closed communities
      were collected, in order to evaluate the prevalence of Legionella and generic
      water quality parameters (Heterotrophic Plate Counts at 22  degrees C and 37 
      degrees C). Samples were tested by culture method for the presence of Legionella.
      Confirmation and identification were carried out through Latex test and PCR.
      Further data about buildings' number of floors and rooms were collected, and put
      in relation to the presence of Legionella through constructing contingency tables
      and performing exact fisher's or Chi-square tests. Cold (< 30  degrees C) water
      samples are analyzed apart.

PMID- 30229111
TI  - Geospatial dataset for analyzing socio-economic regional divergence of European
      regions.
AB  - This data article presents macroeconomic data that can be used for comparative
      territorial studies. The data cover a sample of 413 regions (national
      administrative-territorial units corresponding to second level of a common
      classification of territorial units for statistics of the European Commission -
      NUTS 2 level region of the European Union, and comparable administrative
      territorial units outside the EU) of 48 European countries, including Cyprus,
      Turkey, the European part of Russia, and two partially recognized states - the
      Republic of Kosovo and the Pridnestrovian Moldavian Republic. The statistical
      database covers a five-year period of 2010-2014. This dataset is created to
      enhance our understanding of the contemporary coastalization dynamics in Europe.
      Despite the fact that coastal regions of European countries exhibit an extensive
      level of development and remain attractive to human settlement, industry
      localization, and investment flows their contribution to the socio-economic
      development of Europe is unclear. The reported data cover a series of
      macroeconomic data on key indicators traditionally used in comparative analysis
      of regional development: average annual population, gross regional product (GRP)
      in purchasing power parity (PPP), labor productivity, population density and GRP
      (PPP) values per sq.km. Accounting for differences in geoeconomic position of the
      European regions enables to distinguish four subtypes of regions with a
      particular emphasis on the coastal area: coastal border, coastal other, coastal
      hinterland, and inland other. An additional focus is made on differentiating the
      performance indicators of regions depending on their border geo-economic
      position: border regions with a state border over land, lake or river surface,
      and midland regions - other non-border regions. This data is to be used as a
      comparative benchmark for the coastal border subgroup of regions against the
      totality of border and midland regions.

PMID- 30229112
TI  - The power and interest indicators of the stakeholders of a Water User Association
      around Bengawan Solo River, Indonesia.
AB  - This data article presents the information on stakeholders' power and interest
      indicators in agricultural irrigation management. The data were collected from a
      WUA (Water User Association) called Sekar padi which operates around Bengawan
      Solo river, East Java, Indonesia. This data article contains two major data. The
      first data consists of the power indicator from both primary and secondary
      stakeholders of WUAs. The second data is the stakeholders 'interest indicator of
      WUAs in agricultural irrigation management. The data were collected from
      observations, Focus Group Discussion (FGD) and interview. These data will be
      beneficial for policy makers to determine the suitable programs for agricultural
      irrigation management and for researchers who want to conduct similar studies in
      developing countries.

PMID- 30229113
TI  - Species identification of sunfish specimens (Genera Mola and Masturus, Family
      Molidae) from Australian and New Zealand natural history museum collections and
      other local sources.
AB  - This data-in-brief comprises a summary of sunfish specimens (Genera Mola and
      Masturus, Family Molidae, >29 cm total length) from natural history museum
      collections and other sources, such as strandings, in Australia and New Zealand.
      Each specimen was evaluated morphologically and identified to lowest possible
      taxon based on recent advances in the understanding of the Mola taxonomy.
      References to phylogenetic analyses, where applicable, are included. The summary
      was collated in support of publication Giant jelly eaters on the line: species
      distribution and bycatch of three dominant sunfishes in the Southwest Pacific[1].

PMID- 30229114
TI  - De novo transcriptome resources of the lichens, Dirinaria sp. UKM-J1 and UKM-K1
      collected from Jerantut and Klang, Malaysia.
AB  - Lichen is a symbiotic organism that exists as a single composite body consisting
      of a mycobiont (fungus) and a photobiont (algae or a cyanobacterium). Many lichen
      species are considered as extremophiles due to their tolerance to radiation,
      desiccation, temperature and pollution. However, not all lichen species are
      tolerant to harsh environmental conditions as several species are sensitive for
      example to nitrogen, sulphur, acidity, heavy metals, halogens (e.g. fluoride) and
      ozone. Thus, to better understand why some lichens can withstand exposure to
      pollutants as opposed to those that are susceptible, we focused on the lichen
      species of Dirinaria known for their wide distribution in the tropics, subtropics
      and pantropical, and moderate tolerance to air pollution. Their moderate
      tolerance to air pollution affords them to thrive in good air quality
      environments as well as polluted air environments. Lichen samples of Dirinaria
      sp., UKM-J1 and UKM-K1, were respectively collected from two areas with different
      levels of air quality based on Air Pollutant Index or API (with index pollutant
      criteria of PM10, carbon monoxide, ozone, nitrogen dioxide and sulfur dioxide) in
      the outskirt of Jerantut (UKM-J1), a rural area in the middle of Peninsular
      Malaysia and the township of Klang (UKM-K1), in a busy area of the Klang Valley,
      Malaysia. API was monitored throughout 2012-2013 whereby the sample collection
      site in Klang showed markedly higher concentrations of pollutants in all the
      index pollutant criteria as compared to that of Jerantut. We performed
      transcriptome sequencing using Illumina RNA-seq technology and de novo assembly
      of the transcripts from the lichen samples. Raw reads from both libraries were
      deposited in the NCBI database with the accession number SRP138994.

PMID- 30229115
TI  - Drainage morphometric analysis of the Nagavathi watershed, Cauvery river basin in
      Dharmapuri district, Tamil Nadu, India using SRTM data and GIS.
AB  - A drainage morphometric analysis of Nagavathi watershed in Dharmapuri district
      has been chosen for the present study. Geospatial tools, such as remote sensing
      and GIS, are utilized for the extraction of watershed and its drainage networks.
      The Shuttle Radar Topographic Mission (SRTM) data have been used for drainage
      morphometric analysis and evaluating various morphometric parameters Linear
      aspect, Aerial aspect Relief aspect. The morphometric parameters of Nagavathi
      watershed have been analyzed and evaluated by pioneer methods, such as Horton and
      Strahler. The bifurcation ratio varies from 0.8 to 43.1. The elongation ratio of
      Microwatersheds varies from 0.13 to 0.43, indicates Microwatersheds fall under
      elongated pattern. This study would help the local people to utilize the
      resources for planning rainwater harvesting and watershed management.

PMID- 30229116
TI  - High resolution carbon stock and soil data for three salt marshes along the
      northeastern coast of North America.
AB  - The data presented here includes a table of soils measurements taken at high
      resolution depth intervals (5 cm) for three salt marshes, two along the New
      Brunswick coast of Canada and one on the southern coast of Maine, USA. The data
      includes a table which includes the bulk density, percent organic matter, percent
      organic carbon, carbon stock, and rhizome dominance (if identifiable) at 5 cm
      depth intervals for each soil core. Shapefiles are also included which indicates
      the GPS position of acquired cores and sites where marsh depth was measured but
      no material was recovered. These shapefiles also include marsh peat depth and
      estimates of carbon stock for each point. For further information and
      interpretation of the included data please see the companion research article
      titled "The Importance of Geomorphic Context for Estimating the Carbon Stock of
      Salt Marshes" [1].

PMID- 30229117
TI  - Data on species list and the amount of macrophytes and mobile epi-benthic
      invertebrates in a subtropical seagrass-seaweed mixed bed in Ishigaki Island,
      Japan.
AB  - In April 2014 and 2015, field samplings were conducted in a subtropical seagrass
      seaweed mixed bed in Ishigaki Island, southwest Japan in order to collect
      macrophytes and mobile epi-benthic invertebrates. This article describes
      macrophyte biomass of 16 species or groups and invertebrate abundance of 66
      species or groups. This data is associated with "Phylogenetically diverse
      macrophyte community promotes species diversity of mobile epi-benthic
      invertebrates" (Nakamoto et al., 2018) [1].

PMID- 30229118
TI  - Data on microbial assessment and physicochemical characteristics of sachet water
      samples obtained from three factories in Ota, Ogun state, Nigeria.
AB  - The data described in this article were obtained in a study to assess the
      bacteriological and physicochemical properties of packaged sachet water sold for
      public consumption. Sixty sachet water samples from 3 different brands (A, B and
      C) produced and consumed in Ota, Ogun State was collected. Stratified sampling
      method was used. Samples were subjected to microbiological analysis using pour
      plate method and colony counter to count the organisms. The packaged water
      samples were assessed for the total coliform count, total plate count and count
      on Salmonella- Shigella agar. Physicochemical parameters were also assayed for
      and reported here. The analysis of the data presented here can be helpful in
      improving public health and creating awareness of the risk of consumption of
      satchel water.

PMID- 30229119
TI  - Assessment of prioritizing the effective factors on human resources effectiveness
      (Case study: Tehran Industrial Parks Organization).
AB  - Identifying the effective factors on human resources effectiveness can help
      management and leadership to obtain success, organization goals and fulfillment
      of high effectiveness and efficiency. Thus, they always have to survey the
      effective factors on effectiveness of these valuable and transformational
      resources. Effective factors on employee effectiveness have different aspects and
      varieties. For instance, Hay Group(r) model which is in order to compare
      organizations based on employee effectiveness. The model includes different
      factors located in two groups of ENGAGEMENT and ENABLEMENT. The main purpose of
      this study is to assess and prioritize effective factors on employee
      effectiveness in Tehran Industrial Parks. Furthermore, it is required to be
      surveyed and determined according to organizational properties and content
      dimensions of under study organization, and use of latent knowledge amongst
      organization experts (senior managers). This cross-sectional and descriptive-
      analytical research was performed in 2017. So, it is trying to achieve the
      purposes of study through interview, Delphi method, Multiple Criteria Decision
      Making (MCDM) and Analytical Hierarchy Process (AHP).

PMID- 30229121
TI  - Survey data on digitalization of building procurement process by architectural
      firms in Abuja, Nigeria.
AB  - This data article describes the dataset on the digital technologies and
      applications used by architectural firms in the delivery of building projects.
      The data set was sourced through a questionnaire survey of 75 registered
      architectural firms in Abuja, Nigeria. The survey was conducted between December
      2017 and January 2018 in the study area. The data, which were analyzed using
      descriptive statistics, contain the characteristics of architectural firms in
      Abuja that participated in the survey, the different stand-alone and integrated
      data acquisition, creation, processing, storage and communication/exchange
      technologies, applications and tools and intelligent systems the firms use in
      building procurement process. In addition, the advantages and challenges
      associated with the use of digital technologies in the procurement of building
      projects by architectural firms in the study area are also presented in this
      dataset.

PMID- 30229120
TI  - Data on the origin, course and distribution of the artery to the human
      atrioventricular node.
AB  - This article presents data on the anatomical variation of the origin, course and
      distribution of the artery to the atrioventricular node in humans. The findings
      hold clinical significance for coronary intervention, coronary angiography and
      cardiac pathology in cases of sudden cardiac death. For further interpretation
      and discussion, the original research article 'Clarifying the anatomy of the
      atrioventricular node artery' by Kawashima and Sato (2018) can be referred [1].

PMID- 30229122
TI  - Survey data on supply chain improvement and operational competency of oil and gas
      firms in Nigeria.
AB  - The firm's suppliers are in most social responsibility literature considered a
      branch of the firm's stakeholders that may not necessarily benefit directly from
      the firm's social responsibility practices. However recent studies on CSR from
      the developing country's perspective has highlighted the importance that needs to
      be placed on supply chain improvement. Thus, this article presents data on the
      effect of supply chain improvement as a construct of corporate social
      responsibility on operational competency. The study employed a descriptive
      quantitative research design survey method. The study population consists of 1748
      employees from four top oil and gas firms quoted in the Nigerian stock exchange.
      A sample size of 350 employees were selected. Data was analysed using statistical
      Package for Social Sciences (SPSS). Regression analysis was employed as the
      statistical tool of analysis. The field data set is made widely accessible in
      this article.

PMID- 30229123
TI  - Data on multi-actor parameter design tasks by engineering students with variable
      problem size, coupling, and team size.
AB  - The experiment studies the effect of technical and social sources of complexity
      on effort required to complete abstracted design tasks. Parameter design tasks
      define a set of input design parameters and functional requirements modeled with
      a linear coupling matrix. Selecting design variables to meet all functional
      requirements within error limits completes a task. Technical complexity arises
      from the number and degree of coupling between design parameters. Social
      complexity arises from the number of designers involved in a task. The experiment
      includes 10 sessions with between 19 and 24 rounds of randomly generated
      parameter design tasks each having between two and six design variables and one,
      two, or three designers. Designers completed individual tasks in parallel during
      rounds. This article contains raw and post-processed data from 374 completed
      tasks ranging in effort from a few seconds for simple tasks to more than 15 min
      for complex ones.

PMID- 30229124
TI  - The dataset of scanning electron microscope images of silver nanoparticles formed
      in situ by dopamine chemistry.
AB  - The mussel inspired chemistry of dopamine oxidation to form polydopamine (PDA)
      and in situ reduction of metal ions in solution to form metal nanoparticles have
      widely opened the application of metal nanoparticles surface modification
      technology. This article contains the dataset of the scanning electron microscope
      (SEM) images of silver nanoparticles coated on polyethylene terephthalate (PET)
      films utilizing dopamine chemistry alone or combined with polyvinylpyrrolidone or
      glucose. The Ag NPs formed in various environments present round, cubic, or
      triangle shape. Mendeley Data, http://dx.doi.org/10.17632/bjjrt2dwbn.1.

PMID- 30229125
TI  - The relationship between empowerment, occupational burnout, and job stress among
      nurses in Rasht Medical Education Centers: A dataset.
AB  - The data in this article show the relationship between empowerment, occupational
      burnout and job stress among nurses in medical education centers in the city of
      Rasht, Iran. This descriptive correlational study was carried out from January
      2016 to June 2017. The study sample included 316 nurses working at the teaching
      hospitals in Rasht; they were selected using stratified random sampling. The data
      were collected by a standard questionnaire which was rated based on the five
      point Likert Scale. Data analysis was performed by SPSS-22 and SmartPLS software.
      Data analyzing showed that the mean scores of occupational burnout and job stress
      were lower than the average level. There was a significant relationship between
      empowerment and job stress and between job stress and occupational burnout.
      However, there was no significant association between empowerment and
      occupational burnout. It was discovered that job stress played a mediating role
      on the relationship between empowerment and occupational burnout.

PMID- 30229126
TI  - Scattering-angle-dependent Christiansen color spectra data of poly(vinyl
      chloride) (PVC) suspended in styrene liquid and a comprehensive data list of
      wavelength-dependent refractive indices of PVC.
AB  - This paper reports transmission and scattering spectra of poly(vinyl chloride)
      (PVC) in styrene liquid, which is derived from Christiansen effect. The spectra
      were measured by varying scattering angles. Further discussion on Christiansen
      color was provided in the paper entitled "Transmitting and scattering colors of
      porous particles of poly(vinyl chloride) based on Christiansen effect" (Samitsu
      et al., 2018) [1]. The paper additionally provides refractive indices of PVC
      reported in literatures because Christiansen effect has close relationship with
      wavelength-dependent refractive index, i.e. optical dispersion. The values have
      considerable range probably depending on samples and determination methods for
      refractive index. The comprehensive data list is therefore potentially useful for
      studying refractive index of polymers.

PMID- 30229127
TI  - Data on cadmium removal from synthetic aqueous solution using garbage ash.
AB  - This data article investigates cadmium removal efficiency using garbage ash as a
      cheap and effective adsorbent. Influence of different parameters, such as initial
      cadmium (II) concentration (mg/L), contact time (min), adsorbent dose (gr/L), pH
      and temperature ( degrees C) were investigated. The characterization data of the
      garbage ash was determined using SEM analysis. The experimental data indicated
      that the adsorption of cadmium on garbage ash follows pseudo second order model
      and Langmuir isotherm model with R2 = 0.99. Also, the maximum adsorption capacity
      of adsorbent was 100.25 mg/g. Thermodynamic data showed that cadmium adsorption
      on garbage ash was a spontaneous and endothermic process. Based on acquired data,
      garbage ash could be proposed as an efficient and low-cost adsorbent for the
      removal of cadmium from aqueous solution.

PMID- 30229129
TI  - Dataset for material logistics on construction sites.
AB  - Data in this article describes logistics management on construction sites in
      Abuja, Nigeria. Data was elicited from 55 construction professionals comprising
      of Architects, Builders, Civil Engineers, Project Managers and Quantity
      Surveyors. The Data set in this study consists of responses on: factors affecting
      material purchase on construction sites, factors affecting accuracy of material
      delivery, challenges encountered during material delivery, benefits of material
      delivery on construction sites and methods of forecasting material demand on
      construction sites. This article provides insight into logistics management on
      construction sites in Nigeria and it can be a useful guide for similar research
      in other contexts.

PMID- 30229128
TI  - Data on tumor progression of c-mos deficiency in murine models of KrasG12D lung
      and ApcMin colorectal cancer.
AB  - The c-mos proto-oncogene was one of the first proto-oncogenes to be cloned. Apart
      from its role in meiosis, many efforts have been made to illuminate the
      mechanisms by which c-mos might acts as an oncogene. Increased Mos expression was
      found in most human tumor tissues. However, a detailed role of c-mos in tumor
      progression remains unknown. In this study, we analyzed online databases to find
      out the correlation between Mos expression and poor survival rates in human
      cancer patients. Then, we crossed c-mos knockout mice with ApcMin or KrasG12D
      mice to generate intestinal cancer model and lung cancer model, respectively.
      Tumor progression was monitored, and the influence of c-mos deficiency on cancer
      formation was investigated.

PMID- 30229130
TI  - Current understanding of magnetic resonance imaging biomarkers and memory in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is caused by a cascade of changes to brain integrity.
      Neuroimaging biomarkers are important in diagnosis and monitoring the effects of
      interventions. As memory impairments are among the first symptoms of AD, the
      relationship between imaging findings and memory deficits is important in
      biomarker research. The most established magnetic resonance imaging (MRI) finding
      is hippocampal atrophy, which is related to memory decline and currently used as
      a diagnostic criterion for AD. While the medial temporal lobes are impacted early
      by the spread of neurofibrillary tangles, other networks and regional changes can
      be found quite early in the progression. Atrophy in several frontal and parietal
      regions, cortical thinning, and white matter alterations correlate with memory
      deficits in early AD. Changes in activation and connectivity have been detected
      by functional MRI (fMRI). Task-based fMRI studies have revealed medial temporal
      lobe hypoactivation, parietal hyperactivation, and frontal hyperactivation in AD
      during memory tasks, and activation patterns of these regions are also altered in
      preclinical and prodromal AD. Resting state fMRI has revealed alterations in
      default mode network activity related to memory in early AD. These studies are
      limited in part due to the historic inclusion of patients who had suspected AD
      but likely did not have the disorder. Modern biomarkers allow for more diagnostic
      certainty, allowing better understanding of neuroimaging markers in true AD, even
      in the preclinical stage. Larger patient cohorts, comparison of candidate imaging
      biomarkers to more established biomarkers, and inclusion of more detailed
      neuropsychological batteries to assess multiple aspects of memory are needed to
      better understand the memory deficit in AD and help develop new biomarkers. This
      article reviews MRI findings related to episodic memory impairments in AD and
      introduces a new study with multimodal imaging and comprehensive neuropsychiatric
      evaluation to overcome current limitations.

PMID- 30229133
TI  - Effects of treadmill running in a rat model of chronic kidney disease.
AB  - Chronic kidney disease (CKD) progression results in musculoskeletal dysfunction
      that is associated with a higher likelihood of hospitalization and is predictive
      of hospitalizations and mortality. Despite this, there is a lack of effective
      interventions to treat the musculoskeletal dysfunction. We studied treadmill
      running as an intervention to improve musculoskeletal health in a translational
      rat model that has slowly progressive CKD. CKD rats were subjected to treadmill
      exercise or no treadmill exercise for 10 weeks (n = 8 each group). Animals ran
      for 60 min, 5 times per week starting at a speed of 8 m/min and ending at 18
      m/min (1 m/min increase/week). Treadmill training had no effect on muscle
      strength (assessed as maximally stimulated torque), half-relaxation time (time
      from peak torque to 50%) or muscle cross-sectional area. Overall, there were no
      biochemical improvements related to CKD progression. Skeletal muscle catabolism
      was higher than non-exercised animals without a concomitant change in muscle
      synthesis markers or regeneration transcription factors. These results suggest
      that aerobic exercise, achieved via treadmill running was not protective in CKD
      animals and actually produced potentially harmful effects (increased catabolism).
      Given the high prevalence and dramatic musculoskeletal mobility impairment in
      patients with CKD, there is a clear need to understand how to effectively
      prescribe exercise in order to benefit the musculoskeletal system.

PMID- 30229131
TI  - Antithrombotic therapy in ventricular assist device (VAD) management: From
      ancient beliefs to updated evidence. A narrative review.
AB  - Platelets play a key role in the pathogenesis of ventricular assist device (VAD)
      thrombosis; therefore, antiplatelet drugs are essential, both in the acute phase
      and in the long-term follow-up in VAD management. Aspirin is the most used agent
      and still remains the first-choice drug for lifelong administration after VAD
      implantation. Anticoagulant drugs are usually recommended, but with a wide range
      of efficacy targets. Dual antiplatelet therapy, targeting more than one pathway
      of platelet activation, has been used for patients developing a thrombotic event,
      despite an increased risk of bleeding complications. Although different
      strategies have been attempted, bleeding and thrombotic events remain frequent
      and there are no uniform strategies adopted for pharmacological management in the
      short and mid- or long-term follow up. The aim of this article is to provide an
      overview of the evidence from randomized clinical trials and observational
      studies with a focus on the pathophysiologic mechanisms underlying bleeding and
      thrombosis in VAD patients and the best antithrombotic regimens available.

PMID- 30229135
TI  - Association between stroke-like episodes and neuronal hyperexcitability in MELAS
      with m.3243A>G: A case report.
AB  - *The pathophysiology of the stroke-like episodes of MELAS has not completely been
      elucidated.*Here we report a case of stroke-like episodes, successfully treated
      with levetiracetam.*Neuronal hyperexcitability can be the underlying mechanism of
      stroke-like episodes in MELAS.

PMID- 30229134
TI  - Hemodynamic state of periictal hyperperfusion revealed by arterial spin-labeling
      perfusion MR images with dual postlabeling delay.
AB  - Background: Magnetic resonance imaging (MRI), including perfusion MRI with
      arterial spin labeling (ASL) and diffusion-weighted imaging (DWI), are applied in
      the periictal detection of circulatory and metabolic consequences associated with
      epilepsy. Although previous report revealed that prolonged ictal hyperperfusion
      on ASL can be firstly detected and cortical hyperintensity of cytotoxic edema on
      DWI secondarily obtained from an epileptically activated cortex, the hemodynamic
      state of the periictal hyperperfusion has not been fully demonstrated. Methods
      study-1: We retrospectively analyzed the relationship between seizure
      manifestations and the development of periictal MRI findings, in Case 1 with
      symptomatic partial epilepsy, who underwent repeated periictal ASL/DWI
      examination for three epileptic ictuses (one examination for each ictus). Study
      2: We evaluated the hemodynamic state of periictal hyperperfusion with the ASL
      technique using a dual postlabeling delay (PLD) of 1.5 and 2.5 s in nine
      patients, according to the presence or absence of the localized epileptogenic
      lesion (EL) on conventional 3 T-MRI, who were divided into Group EL+ (six
      patients) and Group EL- (three patients). Results: Study-1 confirmed that the
      stratified representation of the periictal MRI findings depends on the time
      interval between the ictal cessation and MRI examination in addition to the
      magnitude and duration of the epileptic activity. In Study-2, two types of
      periictal hyperperfusion were noted. In all six Group EL+ patients, periictal ASL
      findings showed "fast flow type". Markedly increased ASL signals were noted at
      the epileptically activated cortex, having a tight topographical relationship
      with EL, on ASL with a PLD of 1.5 s, which is decreased on ASL with a PLD of 2.5
      s. In all three Group EL- patients, periictal ASL findings showed "gradual flow
      type", which is characterized by gradual signal increase of the epileptically
      activated cortex on ASL with a PLD of 1.5 and 2.5 s. Conclusion: We confirmed
      that ASL hyperperfusion is superior to DWI in the periictal detection of
      epileptic events. ASL with dual PLD offers the ability to document two types of
      hemodynamics of periictal hyperperfusion.

PMID- 30229132
TI  - Electrophysiological Signature Reveals Laminar Structure of the Porcine
      Hippocampus.
AB  - The hippocampus is integral to working and episodic memory and is a central
      region of interest in diseases affecting these processes. Pig models are widely
      used in translational research and may provide an excellent bridge between
      rodents and nonhuman primates for CNS disease models because of their
      gyrencephalic neuroanatomy and significant white matter composition. However, the
      laminar structure of the pig hippocampus has not been well characterized.
      Therefore, we histologically characterized the dorsal hippocampus of Yucatan
      miniature pigs and quantified the cytoarchitecture of the hippocampal layers. We
      then utilized stereotaxis combined with single-unit electrophysiological mapping
      to precisely place multichannel laminar silicon probes into the dorsal
      hippocampus without the need for image guidance. We used in vivo
      electrophysiological recordings of simultaneous laminar field potentials and
      single-unit activity in multiple layers of the dorsal hippocampus to
      physiologically identify and quantify these layers under anesthesia. Consistent
      with previous reports, we found the porcine hippocampus to have the expected
      archicortical laminar structure, with some anatomical and histological features
      comparable to the rodent and others to the primate hippocampus. Importantly, we
      found these distinct features to be reflected in the laminar electrophysiology.
      This characterization, as well as our electrophysiology-based methodology
      targeting the porcine hippocampal lamina combined with high-channel-count silicon
      probes, will allow for analysis of spike-field interactions during normal and
      disease states in both anesthetized and future awake behaving neurophysiology in
      this large animal.

PMID- 30229136
TI  - Brain and spinal cord MRI lesions in primary progressive vs. relapsing-remitting
      multiple sclerosis.
AB  - Background: Primary progressive (PP) multiple sclerosis (MS) is considered a
      clinically distinct entity from the spectrum of relapsing-remitting (RR) forms of
      the disease. Objective: To compare the presence of brain and spinal cord lesions
      between PP and RR subjects. Methods: We studied people with PPMS [n = 40, 17
      (42.5%) men, age 50.7 +/- 7.7 years, disease duration 10.1 +/- 7.4 years,
      Expanded Disability Status Scale (EDSS) score 4.6 +/- 2.1] and RRMS [n = 40, 12
      (30%) men, age 47.9 +/- 4.2, disease duration 13.7 +/- 5.9, EDSS 1.7 +/- 1.3].
      MRI of the brain and full spinal cord at 1.5T was analyzed to define patients
      having: 1. brain only, 2. spinal cord only, or 3. brain and spinal cord MS
      lesions. Results: Lesions in the brain only were less common in PP (n = 1, 2.5%
      of people) than RR (n = 10, 25%) (Fisher's exact p = 0.007). Lesions in the
      spinal cord only (PP: n = 6, 15%, RR: n = 3, 7.5%, p = 0.481) or brain plus
      spinal cord (PP: n = 33, 83%, RR: n = 27, 68%, p = 0.196) were similar between
      groups. PP had higher EDSS and timed 25-ft walk (Wilcoxon tests, both p < 0.001),
      higher age (t-test p = 0.049), lower disease duration (t-test, p = 0.02), and a
      similar sex ratio (Fisher's exact p = 0.352) vs. RR. Conclusions: We report a
      topographic difference in MRI lesion involvement between PPMS and RRMS. Lesions
      restricted to the brain are more common in RRMS. These findings provide support
      to the notion that PP may have features distinctive from the RR spectrum of the
      disease. Longitudinal comparisons and quantitative MRI analysis would be
      necessary to confirm and extend these results.

PMID- 30229138
TI  - FBXW2 localizes with osteocalcin in bovine periosteum on culture dishes as
      visualized by double immunostaining.
AB  - Osteocalcin (OC) is a well-known protein related to bone, however, the role of F
      box and WD-40 domain-containing protein 2 (FBXW2) in bone remains unclear. In
      2016, the presence of FBXW2 in bovine periosteum was reported. In this study,
      double immunostaining was used to investigate the relationship between OC and
      FBXW2. FBXW2 showed tubular structures, and OC showed a similar localization
      pattern as FBXW2. Double immunostaining findings suggested that FBXW2 tubes were
      coated with OC. To the author's knowledge, this is the first study to reveal the
      interaction between OC and FBXW2.

PMID- 30229137
TI  - In vivo regeneration functionalities of experimental organo-biomaterials
      containing water-soluble nacre extract.
AB  - Background: Novel multifunctional biomaterials were recently designed to allow
      for an optimized tissue regeneration process. Purpose: To comprehensively assess
      (photographic, radiographic and histological) the in vivo functionality of
      demineralized bovine bone matrix (DBM) associated with an experimental marine
      organic extract (MOE) from nacre in a sheep ectopic grafting model. Materials and
      methods: Synthesis of MOE was based on mixing powdered nacre (0.05 g, particles
      average size <0.1 mm) with acetic acid (5 mL, pH 7) under constant stirring for
      72 hours (25  degrees C). Polyethylene tubes (3/animal, n = 4, diameter: 5.0 mm *
      length: 10.0 mm) from the control (empty) or experimental groups (DBM or DBM +
      MOE) were then intramuscularly implanted into the lumbar regions of sheep (n = 8,
      2-years old, ~45 kg). Animals were euthanized at 3 and 6 months to allow for the
      collection of tissue samples. Tissue samples were fixed in formalin 10%
      (buffered, 7 days) in preparation for photographic, radiographic and histological
      assessments. Acquired images were then analyzed using digital image analysis
      software to quantify the amount of neoformed tissues, whereas radiographic and
      histological analyses were performed to determine radiopacity and classification
      of tissues deposited inside of the tubes. Results: Photographic and radiographic
      analyses have shown that both pure (unaltered) and MOE-modified DBM were capable
      of depositing neoformed tissues (at 3 and 6 months), where higher levels of
      deposition and radiopacity were observed on groups treated with experimental
      materials. Histological results, however, demonstrated that tissues formed from
      both unaltered and MOE-modified DBM were only fibrous connective in origin.
      Conclusions: As an ectopic grafting in sheep, the experimental organo-biomaterial
      association applied did not reveal any osteoinductive property but led to a
      fibrous tissue repair only.

PMID- 30229139
TI  - Effect of brewery spent diatomite sludge on trace metal availability in soil and
      uptake by wheat crop, and trace metal risk on human health through the
      consumption of wheat grain.
AB  - Soil plays a crucial role in food safety as it determines the composition of food
      at the beginning of the food chain. However, the quality of soil resources in
      terms of their potential impact on human health caused by harmful elements is
      poorly understood in Ethiopia due to lack of reliable and appropriate
      experimental data. In this study, a field experiment was conducted to evaluate
      trace metal accumulation in soils amended with brewery spent diatomite sludge
      (BSDS) in comparison to control, recommended inorganic fertilizers (RIF) and
      integrated BSDS & RIF (BSDS:RIF). Trace metals uptake by wheat crop and the
      degree of soil contamination, and human health risk were investigated. BSDS
      application significantly increased the concentration of trace metals (Cu, Zn, Pb
      and Ni) in soil compared to that in the control, the RIF, and BSDS:RIF
      applications. It also significantly increased the concentration of Cu, Zn, Pb and
      Ni in the wheat grain compared to that in the control and the RIF, but the
      increase was not significantly different from that in BSDS:RIF amendment. All
      trace metal concentrations in soil and wheat grain (except Pb in wheat grain)
      were below the maximum permissible limits in some European countries of
      agricultural soils, and the maximum permissible limit of FAO/WHO. The degree of
      soil contamination from each of the treatments was below the maximum acceptable
      degree of contamination. The Health Risk Index (HRI) was <1 for all metals in all
      treatments. Thus, we conclude that consumption of wheat grain grown on soils
      amended with BSDS and BSDS:RIF has no human risks and has low likelihood of human
      exposure to trace metals.

PMID- 30229140
TI  - Autoimmune retinopathy and optic neuropathy associated with enolase-positive
      renal oncocytoma.
AB  - Purpose: To report a case of autoimmune retinopathy and optic neuropathy
      associated with an enolase-positive renal oncocytoma. Observations: A 41-year-old
      man presented with subacute, painless, bilateral vision loss. On initial
      examination, visual acuity measured 20/125 OD and 20/1250 OS, and telangiectatic
      vessels were noted on the optic nerves and in the maculae. Goldmann perimetry
      showed bilateral, cecocentral scotomas, and electroretinography demonstrated
      reduced photopic and scotopic signals, concerning for autoimmune retinopathy.
      Serum testing showed multiple positive anti-optic nerve and anti-retinal
      antibodies, including to alpha-enolase. Extensive systemic workup was negative
      except for a large, exophytic, right renal mass. Biopsy was consistent with a
      benign oncocytoma, and immunohistochemical staining showed diffusely positive
      alpha-enolase staining. The patient was treated with a five-day course of
      intravenous methylprednisolone and plasmapheresis with minimal improvement.
      Surgical excision of the oncocytoma was performed. At 9-months post-operatively,
      visual acuity had improved to 20/40 OU, with corresponding improvement on visual
      field and electroretinography testing. Conclusions and importance: To our
      knowledge, this is the first report of autoimmune retinopathy and optic
      neuropathy associated with a renal oncocytoma. The case highlights the importance
      of a thorough systemic workup in cases of suspected autoimmune retinopathy and
      reminds clinicians that even tumors considered benign can have distal effects on
      other organs.

PMID- 30229141
TI  - Quality and Safety-The View from the Corner Office.

PMID- 30229142
TI  - Moving the Needle in Children's Health with National Collaborative Networks-A
      CEO's Perspective.

PMID- 30229143
TI  - Let the Journey Begin.

PMID- 30229144
TI  - Envisioning the Future Morbidity and Mortality Conference: A Vehicle for Systems
      Change.

PMID- 30229145
TI  - Standardization of Postoperative Transitions of Care to the Pediatric Intensive
      Care Unit Enhances Efficiency and Handover Comprehensiveness.
AB  - Introduction: To determine the impact of standardization of postoperative
      transitions of care to the pediatric intensive care unit on handover efficiency
      and the quality of healthcare data exchange. Methods: This was a prospective, pre
      post observational study after standardization of postoperative transitions in a
      44-bed pediatric intensive care unit in a 313-bed tertiary care pediatric
      hospital from April to July 2015. Standardization was completed using a
      multidisciplinary handover checklist. Primary outcomes were efficiency expressed
      as mean handover duration and the comprehensiveness of healthcare data exchange.
      Results: Forty-seven postoperative transitions were observed of which 23 were
      preintervention and 24 were postintervention. After standardization, efficiency
      improved from 10.5 +/- 5.4 to 7.8 +/- 2.7 minutes (P < 0.05). Healthcare data
      exchanged between surgical, anesthesia, and critical care providers were more
      robust including intraoperative, historical, and anticipatory guidance (all P <
      0.05). After intervention, attendance through completion of handover for surgical
      services increased from 13% to 88% (P < 0.05). Conclusions: Standardization of
      postoperative transitions improved efficiency, healthcare data exchange, and
      anticipatory planning. Future research is required to link standardization of
      transitions to improved patient outcomes and measure the development of shared
      mental models.

PMID- 30229146
TI  - Impact of a Longitudinal Quality Improvement and Patient Safety Curriculum on
      Pediatric Residents.
AB  - Introduction: The effectiveness of longitudinal quality/safety resident curricula
      is uncertain. We developed and tested our longitudinal quality improvement (QI)
      and patient safety (PS) curriculum (QIPSC) to improve resident competence in
      QI/PS knowledge, skills, and attitudes. Methods: Using core features of adult
      education theory and QI/PS methodology, we developed QIPSC that includes self
      paced online modules, an interactive conference series, and mentored projects.
      Curriculum evaluation included knowledge and attitude assessments at 3 points in
      time (pre- and posttest in year 1 and end of curriculum [EOC] survey in year 3
      upon completion of all curricular elements) and skill assessment at the EOC.
      Results: Of 57 eligible residents in cohort 1, variable numbers of residents
      completed knowledge (n = 42, 20, and 31) and attitude (n = 11, 13, and 37)
      assessments in 3 points in time; 37 residents completed the EOC skills
      assessment. For knowledge assessments, there were significant differences between
      pre- and posttest and pretest and EOC scores, however, not between the posttest
      and EOC scores. In the EOC self-assessment, residents' attitudes and skills
      improved for all areas evaluated. Additional outcomes from project work included
      dissemination of QI projects to hospital-wide quality/safety initiatives and in
      peer-reviewed national conferences. Conclusions: Successful implementation of a
      QIPSC must be responsive to a number of learners, faculties, and institutional
      needs and integrate adult learning theory and QI/PS methodology. QIPSC is an
      initial effort to address this need; follow-up results from subsequent learner
      cohorts will be necessary to measure the true impact of this curriculum: behavior
      change and practice improvements.

PMID- 30229147
TI  - Return to Drive Counseling After Sports-Related Concussion: A Quality Improvement
      Project.
AB  - Introduction: Concussion is a common injury in adolescent athletes, many of whom
      also drive. Counseling athletes and their families about driving risks post
      concussion is a potentially significant intervention. The aim of this quality
      improvement project was to increase driving recommendations for concussed
      athletes in a pediatric sports medicine clinic. Methods: Patients in this quality
      improvement project were seen in the sports medicine concussion clinic between
      February 2014 and August 2015. We determined how often driving recommendations
      were documented through a retrospective chart review. Once the "return to drive"
      project was introduced to the sports medicine staff, multiple interventions were
      completed including handing out flyers to remind families about driving and
      creating changes to the electronic medical record. Results: At baseline, 9.3% of
      visits had driving recommendations documented. After an intervention requiring
      clinical documentation in the electronic medical record, 97% of patients received
      driving recommendations. Conclusions: The quality improvement effort was
      successful at increasing the frequency of delivery of appropriate driving
      recommendations provided to concussed athletes.

PMID- 30229148
TI  - Simulation to Predict Effect of Citywide Events on Emergency Department
      Operations.
AB  - Medical emergency preparedness has been an issue of medical relevance since the
      advent of hospital care. Studies have simulated emergency department (ED)
      overcrowding but not yet characterized effects of large-scale, planned events
      that drastically alter a city's demography, such as in Philadelphia, Pennsylvania
      during the 2015 World Meeting of Families. A discrete event simulation of the ED
      at the Children's Hospital of Philadelphia was designed and validated using past
      data. The model was used to predict the patient length of stay (LOS) and number
      of admitted patients if the arrival stream to the ED were to change by 50% from
      typical arrivals in either direction. We compared the model's estimations with
      data produced during the papal visit that had 39.65% fewer patient arrivals. For
      validation, the simulated mean LOS was 226.1 +/- 173.3 minutes (mean +/- SD) for
      all patients and 352.1 +/- 170.3 minutes for admitted patients. Real-world mean
      LOSs for the fiscal year 2014 were 230.6 +/- 134.8 for all patients and 345.0 +/-
      147.7 for admitted patients. For the estimation of the World Meeting of Families,
      the simulation accurately estimated the LOS of both patients overall and admitted
      patients within 10%. These results show that it is possible to use simulations to
      project the patient flow effects in EDs in case of large-scale events. Providing
      efficient care is essential to emergency operations, and projections of demand
      are crucial for targeting appropriate changes during large-scale events. Analysis
      of validated computer simulations allows for evidence-based decision making in a
      complex clinical environment.

PMID- 30229149
TI  - Set of Quality Indicators of Pediatric Intensive Care in Spain: Delphi Method
      Selection.
AB  - Introduction: This study objective was to identify, select, and define a basic
      set of quality indicators for pediatric intensive care in Spain. Methods: (1)
      Review of the literature to identify quality indicators and their defining
      elements and (2) selection of indicators by consensus of a group of experts using
      basic Delphi methodology (2 rounds) and forms distributed by email among experts
      from the Spanish society of pediatric intensive care. Results: We selected
      quality indicators according to their relevance and feasibility and the experts'
      agreement on their incorporation in the final set. We included only those
      indicators whose assessment was within the highest tertile and greater than or
      equal to 70% evaluator agreement in the final selection. Starting from an
      initially proposed set of 136 indicators, 31 experts first selected 43 indicators
      for inclusion in the second round. Twenty indicators were selected for the final
      set. This "top 20" set comprised 9 process indicators, 9 of results (especially
      treatment-associated adverse effects), and 2 indicators of structure. Several of
      them are classical indicators in intensive care medicine (rates of hospital
      acquired infections, pressure ulcers, etc.), whereas others are specifically
      pediatric (eg, unrestricted parent visitation or training the parents of
      technology-dependent children). Conclusions: We reached a consensus on a set of
      20 essential quality indicators for pediatric intensive care in Spain. A
      significant subset reflects the peculiarities of pediatric care. We consider this
      subset as a starting point for future projects of network collaboration between
      pediatric intensive care units in Spain.

PMID- 30229150
TI  - Optimizing a Nurse-led Transitional Home Visit Program in Preparation for a
      Randomized Control Trial.
AB  - Introduction: The Hospital to Home Outcomes study began with the end goal of
      evaluating the effectiveness of a single, nurse-led transitional home visit (home
      visit) program, for acutely ill, pediatric patients, which had been piloted at
      our institution. As part of the overall study design, building on prior
      randomized control trials that utilized a run-in period prior to the trial, our
      study team designed an optimization period to test the home visit and study
      procedures under real-world conditions. Methods: For this optimization project,
      there were 3 process improvement goals: to improve the referral process to the
      home visit, to optimize the home visit content, and to define and operationalize
      measures of patient- and family-centered outcomes to be used in the subsequent
      randomized control trial. During the optimization period, a multidisciplinary
      study team met weekly to review family and stakeholder feedback about the
      iterative modifications made to the home visit process, content, and outcome
      measures. Results: Optimization home visits were completed with 301 families
      across a variety of discharge diagnoses. The outcomes planned for the clinical
      trial were tested and refined. Feedback from families and stakeholders indicated
      that the content changes made to the home visits resulted in increased family
      knowledge of warning signs to monitor postdischarge. Thirty-one percent of
      families reported that they altered the care of their child after the home visit.
      Conclusion: Through iterative testing, informed by multistakeholder feedback, we
      leveraged patient and family engagement to maximize the effectiveness and
      generalizability of the home visit intervention.

PMID- 30229151
TI  - A Quality Improvement Initiative to Standardize Use of Inhaled Nitric Oxide in
      the PICU.
AB  - Background: Inhaled nitric oxide (iNO) is a potent pulmonary vasodilator used off
      label to treat refractory hypoxemia in the pediatric intensive care unit (PICU).
      However, clinical practice varies widely, and there is limited evidence to
      support this expensive therapy. Our objective was to test whether implementation
      of a clinical guideline for iNO therapy would decrease practice variability,
      reduce ineffective iNO utilization, and control iNO-related costs. Methods: We
      used quality improvement (QI) methodology to standardize the use of iNO in a
      single quaternary care PICU (noncardiac). All PICU patients receiving iNO therapy
      between January 1, 2010, and December 31, 2013, were included. The QI
      intervention was the development and implementation of a clinical guideline for
      iNO initiation, continuation, and weaning. iNO use was monitored using
      statistical process control charts. Results: We derived baseline data from 30
      preguideline patients (35 separate iNO courses) compared with 33 postguideline
      patients (36 separate iNO courses). Despite similar baseline characteristics,
      disease severity, and degree of hypoxemia, postguideline patients had a shorter
      median [interquartile range (IQR)] duration of iNO therapy than preguideline
      patients [76 (48-124) hours versus 162 (87-290) hours; P < 0.0001]. We have
      sustained the reduced iNO usage throughout the postguideline period.
      Postguideline patients also had improved provider documentation and a median iNO
      cost savings of $4,600. Conclusions: Implementation of iNO usage guidelines was
      associated with decreased iNO usage and cost of iNO therapy in the PICU.

PMID- 30229152
TI  - Impact of a Pressure Injury Prevention Bundle in the Solutions for Patient Safety
      Network.
AB  - Background: Our objective was to describe changes in pressure injury (PI) rates
      in pediatric hospitals after implementation of an active surveillance and
      prevention bundle and to assess the impact of bundle elements. Methods: The
      Children's Hospitals Solutions for Patient Safety (SPS) Network is a learning
      collaborative working together to eliminate harm to hospitalized children. SPS
      used a 3-pronged approach to prevent pressure injuries: (1) active surveillance,
      (2) implementing and measuring compliance with the prevention bundle, and (3)
      deploying a wound ostomy team. Among hospitals participating since 2011 (phase
      1), we used negative binomial analyses to assess change in PI rates. Only phase 1
      hospitals had a baseline period before any prevention bundle intervention. Among
      all hospitals participating in 2013 (phases 1 and 2), we used funnel charts to
      assess the association between reliable bundle implementation and PI rates.
      Results: Among the 33 hospitals that participated in SPS from 2011 to 2013 (phase
      1), the rate of stage 3 pressure injuries declined from 0.06 to 0.03 per 1,000
      patient-days (P < 0.001). Stage 4 pressure injuries declined from 0.01 to 0.004
      per 1,000 patient-days (P = 0.02). Among all 78 hospitals in phases 1 and 2, the
      cohort that adopted each bundle element, measured compliance, and achieved 80%
      prevention bundle compliance had significantly lower PI rates compared with all
      hospitals. Conclusions: SPS hospitals saw a significant reduction in stage 3 and
      4 PIs over a 2-year period. Reliable implementation of each element of a
      prevention bundle was associated with lower PI rates.

PMID- 30229154
TI  - Variation in Gentamicin Dosing and Monitoring in Pediatric Units across New South
      Wales.
AB  - Introduction: Gentamicin is an aminoglycoside antibiotic with broad-spectrum
      bactericidal activity and is widely used in pediatric units to treat infection
      with susceptible organisms. This study aimed to describe the dosage regimen for
      gentamicin and approach to its therapeutic drug monitoring (TDM) among the
      pediatric units within the state of New South Wales (NSW). Methods: A
      questionnaire was sent electronically to representatives of 40 pediatric units in
      NSW, requesting details of each unit's gentamicin dosing and TDM policy. Results:
      A total of 35 units responded to the survey. The majority (63%) of the units used
      a dose of 7.5 mg/kg of gentamicin in patients with normal renal function. More
      than half of the units (54%) did not have a local gentamicin dosing protocol and
      relied on other sources for dosing regimens. Dosing responses varied from a dose
      of 6 mg/kg once daily for patients more than 10 years of age to 7 mg/kg once
      daily on day 1, followed by 5 mg/kg once daily for patients over 10 years of age.
      For TDM of gentamicin, 63% of units indicated use of trough levels and 23% units
      used the Hartford Nomogram. Conclusions: A significant variation exists in
      clinical practice among pediatric units in NSW on gentamicin dosing and TDM
      guidelines. There is an urgent need for collaboration among nursing, medical, and
      pharmacy experts to achieve consensus to develop and adopt statewide uniform
      guidelines on gentamicin dosing and TDM.

PMID- 30229153
TI  - Reduced Necrotizing Enterocolitis after an Initiative to Promote Breastfeeding
      and Early Human Milk Administration.
AB  - Introduction: We sought to reduce the incidence of necrotizing enterocolitis
      (NEC) in premature infants (PI) by fostering the postnatal establishment of
      protective intestinal bacteria through early administration of human milk (HM)
      and probiotics. Methods: A multidisciplinary team implemented an initiative to
      support breastfeeding (BF) and provide early postnatal supplemental donor human
      milk (DHM) and probiotics to PI. Interventions included process improvements in
      milk preparation, storage, and fortification. PI admitted to our NICU between
      2006 and 2015 were monitored for feeding of HM, DHM, and preterm formula (PF),
      frequency of early feedings, and incidence of NEC. Results: Retrospective review
      of 2557 cases revealed post-initiative increases in the percentage of PI
      receiving HM (91.5% to 96.1%), HM within 48 hours of birth (75% to 90.6%), and
      DHM (17.7% to 71.9%). The percentage of infants receiving feedings on day one
      increased from 23.9% to 44.6% while the percentage receiving PF within the first
      72 hours declined (31.2% to 10.3%). The NEC rate declined from 4.1% to 0.4%.
      Reduction in NEC occurred despite a simultaneous increase in perinatal antibiotic
      exposure and the universal but late administration of bovine HM fortifier. The
      improvement associated with the decrease in NEC included initiation of probiotic
      administration, a reduction in PF feeding, and improvements in milk preparation,
      storage, and fortification processes. Conclusions: Early exclusive feedings of HM
      and avoidance of PF together with probiotics and milkhygiene may decrease NEC in
      PI. Neither brief perinatal antibiotic exposure nor late introduction of bovine
      fortifiers appears detrimental in this context.

PMID- 30229155
TI  - Pediatric Gastrostomy Tube Placement: Lessons Learned from High-performing
      Institutions through Structured Interviews.
AB  - Introduction: Gastrostomy tube (GT) placement is one of the most common
      operations performed in children, and it is plagued by high complication rates.
      Previous studies have shown variation in readmission and emergency room visit
      rates across different children's hospitals, with both low and high outliers.
      There is an opportunity to learn how to optimize outcomes by identifying
      practices at high-performing institutions. Methods: Surgeons and nurses routinely
      involved in GT care at 8 high-performing pediatric centers were identified. We
      conducted structured interviews focusing on the approach to GT education,
      technical aspects of GT placement, and postoperative management. Summary
      statistics were performed on quantitative data, and the open-ended responses were
      analyzed by 2 independent reviewers using content analysis. Results: Several
      common practices among high-performing centers were identified (standardized
      approach to education, availability by phone and in clinic to manage GT-related
      issues, and empowering families to feel confident with troubleshooting and
      dealing with GT problems). There was substantial variation in operative technique
      and postoperative care. The participants expressed that technical aspects of
      operative placement and postoperative management of feedings and common
      complications are not as important as education, availability, and empowerment in
      optimizing outcomes. Conclusions: We have identified common themes among
      pediatric centers with favorable outcomes after GT placement. Identifying which
      components of GT care are associated with optimal outcomes is critical to our
      understanding of current practice and may help identify opportunities to improve
      care quality.

PMID- 30229156
TI  - Is the "July Effect" Real? Pediatric Trainee Reported Medical Errors and Adverse
      Events.
AB  - Introduction: The "July Effect" suggests an increase in patient adverse events in
      July compared with other months due to the introduction of new providers
      throughout the training continuum. The aim of this initiative was to analyze
      reported pediatric trainee medical errors from May through September 2015 at a
      tertiary care free-standing academic children's hospital to determine if there
      were more reported medical errors and more adverse events from those errors in
      July. Methods: An error surveillance system is used to report and track near
      misses, adverse events, and medical errors. Three of the authors reviewed each
      report, which was electronically collected in the institution during the time
      period of interest. The reported medical error incidence per 1,000 trainee-days
      was compared against those in July for a significant difference. Results: There
      are a total of 282 trainees (86 pediatric residents, 81 nonpediatric residents,
      and 115 fellows) who are clinically active in the hospital at any given month.
      Pediatric residents had more reported medical errors in July (31) compared with
      May (16; P = 0.015), June (16; P = 0.019), and August (19; P = 0.046). There was
      no significant difference in the number of adverse events from reported medical
      errors by trainees in July (7) compared with May (5), June (8), August (4), or
      September (8; P > 0.2). Conclusion: In this single-center evaluation, there is an
      increase in reported medical errors involving pediatric residents in July
      compared with the months surrounding July. However, there is no difference in
      numbers of adverse events from those errors between these months.

PMID- 30229157
TI  - Quality Improvement in Pediatric Head Trauma with PECARN Rules Implementation as
      Computerized Decision Support.
AB  - Background: For the 1.4 million emergency department (ED) visits for traumatic
      brain injury (TBI) annually in the United States, computed tomography (CT) may be
      over utilized. The Pediatric Emergency Care Applied Research Network developed 2
      prediction rules to identify children at very low risk of clinically important
      TBI. We implemented these prediction rules as decision support within our
      electronic health record (EHR) to reduce CT. Objective: To test EHR decision
      support implementation in reducing CT rates for head trauma at 2 pediatric EDs.
      Methods: We compared monthly CT rates 1 year before [preimplementation (PRE)] and
      1 year after [postimplementation (POST)] decision support implementation. The
      primary outcome was change in CT use rate over time, measured using statistical
      process control charts. Secondary analyses included multivariate comparisons of
      PRE to POST. Balancing measures included ED length of stay and returns within 7
      days after ED release. Results: There were 2,878 patients with head trauma (1,329
      PRE and 1,549 POST) included. Statistical process control charts confirmed
      decreased CT rates over time POST that was not present PRE. Secondary statistical
      analyses confirmed that CT scan utilization rates decreased from 26.8% to 18.9%
      (unadjusted Odds Ratio [OR], 0.64; 95% Confidence Interval [CI], 0.53 -0.76;
      adjusted OR, 0.71; 95% CI, 0.58 -0.86). Length of stay was unchanged. There was
      no increase in returns within 7 days and no significant missed diagnoses.
      Conclusions: Implementation of EHR-integrated decision support for children with
      head trauma presenting to the ED is associated with a decrease in CT utilization
      and no increase in significant safety events.

PMID- 30229158
TI  - An Intervention to Improve Caregiver Adherence to Oral Rehydration Therapy.
AB  - Objective: To improve oral rehydration therapy (ORT) after discharge for children
      presenting to the emergency department (ED) with acute gastroenteritis (AGE).
      Methods: We designed and implemented a quality improvement initiative to improve
      caregiver adherence to ORT in children 6 months to 21 years old with AGE. The
      intervention consisted of ORT "kits" with rehydration supplies and caregiver
      instructions. In the preintervention period we monitored patient/caregiver
      adherence to ORT recommendations and additionally monitored ORT kit and
      educational material distribution during the intervention phase via a caregiver
      survey after discharge. We utilized statistical process control methodology to
      assess responses to the intervention. As a balancing measure, we monitored the ED
      length of stay for patients with AGE. Results: Over the study period from
      November 2013 to April 2015, we included 174 encounters during the
      preintervention period and 256 encounters during the intervention period. More
      than 9 of 10 children received ORT kits in the intervention period. Self-reported
      adherence to ORT between the 2 time periods remained constant. The ED length of
      stay did not change between the preintervention and intervention period.
      Conclusions: Despite successful distribution of novel ORT materials and education
      for caregivers of children with AGE in a pediatric ED, caregiver self-reported
      adherence to ORT postdischarge visit was unchanged. An unexpected high baseline
      adherence to ORT practices may have limited improvement.

PMID- 30229159
TI  - A Quality Improvement Intervention Reduces the Time to Administration of Stat
      Medications.
AB  - Introduction: The delivery of urgent ("stat") medications to hospitalized
      children is important for safe quality care. The goal of this study was to
      evaluate the effect of a set of interventions on the percentage of stat
      medications administered within 30 minutes of ordering. Methods: A pre-post study
      in 2 pediatric units (36 beds) in a private hospital in Saudi Arabia between
      January 2015 and September 2016. Interventions included structured communication
      requirements, introduction of a dedicated electronic inbox for stat medication
      orders sent by nurses to the pharmacy, and the use of a pink envelope for the
      delivery of stat medications. A multivariate logistic regression model was used
      to model percentage of medications administered within goal. Results: Three
      hundred four stat orders met inclusion criteria. The proportion of orders meeting
      the 30-minute goal increased from a mean of 20% to a mean of 49% after the
      interventions (P < 0.001). In the final month of the study, compliance reached a
      peak of 67%. The mean turnaround time from ordering to the administration of the
      medication decreased from 59.7 to 40.7 minutes (P < 0.001). On multivariate
      analysis, medication type and unit-based availability of medications were
      statistically significant predictors of turnaround time. The odds of compliance
      being achieved was 0.3 times less if the medication was not available on the
      unit. Conclusions: A set of interventions significantly increased the percentage
      of stat medications delivered within 30 minutes.

PMID- 30229161
TI  - The Promising Contributions of Behavioral Economics to Quality Improvement in
      Health Care.

PMID- 30229160
TI  - Improving the Performance of Anthropometry Measurements in the Pediatric
      Intensive Care Unit.
AB  - Introduction: Obtaining anthropometry measurements in critically ill children is
      challenging. Our objective was to improve the process of obtaining anthropometry
      measurements in the pediatric intensive care unit (PICU; even if previously
      obtained) using a dedicated PICU nutrition support team (NST). Methods: PICU
      staff were trained to perform anthropometry measurements through online
      education, skills training, and just-in-time bedside teaching by the PICU NST.
      Equipment was upgraded and standardized throughout the PICU along with
      implementation of preselected orders in the electronic medical record. Data were
      collected before and immediately after intervention and at monthly intervals from
      12 to 36 months to test sustainability of practice change. PICU staff were
      surveyed on barriers to anthropometry measurements at 36 months after initial
      intervention. Results: Compared with baseline, the intervention resulted in more
      patients with orders for weight, stature, and head circumference (all P < 0.001)
      at PICU admission. Correspondingly, more patients had measurements of weight (P =
      0.04), stature (P = 0.01), and head circumference (P = 0.009) at PICU admission.
      For long-stay patients (>7 days), compliance improved with measurements of serial
      weights (P = 0.002), stature (P < 0.001), and head circumference (P = 0.02).
      Between 12 and 36 months after the intervention, there was a noticeable trend to
      increases in weight measurements at PICU admission, and to a lesser extent, of
      stature and head circumference. Competing clinical priorities were a key barrier
      to anthropometry measurements. Conclusions: Performance of anthropometry
      measurements in the PICU can be improved by a dedicated PICU NST; however,
      sustaining these improvements is challenging due to competing clinical
      priorities.

PMID- 30229162
TI  - Improving Apparent Cause Analysis Reliability: A Quality Improvement Initiative.
AB  - Introduction: Apparent cause analysis (ACA) is a process in quality improvement
      used to examine events. A baseline assessment of completed ACAs at a tertiary
      care free-standing pediatric academic hospital revealed they were ineffective due
      to low-quality analysis, unreliable action plans, and poor spread, leading to
      error recurrence. The goal of this project was to increase ACA action plan
      reliability scores while maintaining or decreasing turnaround time. Methods: The
      Model for Improvement served as the framework for this quality improvement
      initiative. We developed a key driver diagram, established measures, tested
      interventions using plan- do-study-act cycles, and implemented the effective
      interventions. To measure reliability, we created a high reliability toolkit that
      links each action item/intervention to a level of reliability and scored each ACA
      action plan to determine overall reliability score. Action plans scored as low
      level of reliability required revision before implementation. Results: Average
      ACA action plan reliability scores increased from 86.4% to 96.1%. ACA turnaround
      time decreased from a baseline of 13 days to 8.6 days. Stakeholders reported a
      subjective increase in satisfaction with the revamped ACA process. Conclusions:
      Incorporating high reliability principles into ACA action plan development
      increased the effectiveness of ACA while decreasing turnaround time. The high
      reliability toolkit was instrumental in providing an organizational resource for
      approaching this subset of cause analyses. The toolkit provides a way for
      safety/quality leaders to connect with stakeholders to design highly reliable
      solutions that improve safety for patients, families, and staff.

PMID- 30229163
TI  - Long-Term Sustainability of Timely Emergency Department Analgesia for Fractures:
      A Time Series Study.
AB  - Objectives: To determine the long-term sustainability and unintended consequences
      of a quality improvement project to improve the timeliness of intravenous (IV)
      opioid administration to patients with long-bone extremity fractures within a
      dynamic pediatric emergency department. Methods: A retrospective study of
      patients with long-bone extremity fractures was conducted using electronic
      medical record data from 2007 to 2014. The primary outcome was the percentage of
      patients receiving timely IV opioids. Control charts and time series models were
      used to determine if changes in the clinical microenvironment were associated
      with shifts in the outcome measure. Unintended consequences included patients
      receiving potentially avoidable IVs and use of the quality improvement process
      for patients without long-bone extremity fractures. Results: Improved timeliness
      of IV opioids was sustained. The type of physician who staffed the process and
      optimization of faculty staffing hours were associated with a 9.6% decrease and
      11.8% increase in timely IV opioids, respectively. Implementation of the IV
      opioid process was not associated with increased placement of potentially
      avoidable IVs. Of patients receiving the IV opioid process, 22% did not have a
      long-bone extremity fracture, of whom 91% were diagnosed with a different painful
      injury. Conclusion: Sustainability of IV opioid timeliness was robust, despite
      changes in the clinical microenvironment. Changes in physician staffing and
      responsibilities in a pediatric emergency department may be especially important
      to consider when planning future improvement initiatives. Our findings support
      the importance of higher reliability interventions, such as identification and
      utilization of existing patterns of behavior, as high yield for sustaining
      outcomes.

PMID- 30229164
TI  - Identification of Critical to Quality Elements for Intensive Care Rounds by Kano
      Analysis.
AB  - Background: Pediatric cardiac intensive care unit rounds require high levels of
      efficiency in data transfer and decision making to achieve optimal performance.
      Traditional survey methods do not discriminate and prioritize effectively the
      elements of rounds essential to a provider. In this study, we describe our
      experience with a novel survey method (Kano analysis) to assess customers'
      (surgeons, intensivists, cardiologists, advanced practice nurses, and nurses)
      requirements from rounds. Methods: A 26-point survey divided into 3 domains
      (presentation, decision, and process elements) was conducted among Pediatric
      Intensive Care Unit (PICU) providers. Based on the survey, attractive, must be,
      performance, indifferent, and reverse categories were identified using methods
      described in the literature. Average satisfaction and dissatisfaction
      coefficients and percentages of attractive and mandatory elements in subgroups
      were compared. Results from the quantitative analysis were charted on a
      categorization plane. Results: The survey was returned by all providers with 96%
      valid responses. The highest satisfaction coefficient in the presentation domain
      was for "one line statement about the patient" (0.76), in the decision domain
      "rhythm/anti-arrhythmics" (0.54), and in the process domain "reformatting
      presentation script" (0.77). The highest dissatisfaction gradients were for
      "overnight events" (-0.91), "rhythm/anti-arrhythmics" (-0.71), and "asking
      families to join rounds" (-0.49). Among the 5 subgroups, surgeons required the
      largest percentage of items as mandatory or attractive and had the highest
      dissatisfaction coefficients in all 3 categories. Conclusion: Kano survey can
      provide rapid and precise actionable data to restructure a new process. Further
      research potentially also involving patients and families in the Kano survey may
      provide insight on patient-centered care models.

PMID- 30229165
TI  - Feasibility of Episode-Based Bundled Payment for a Pediatric Surgical Condition:
      Posterior Spinal Fusion.
AB  - Introduction: Episode-based bundled payment (EBBP) is an alternative model of
      health-care payment that aims to align providers' and hospitals' incentives
      toward delivery of more coordinated, higher quality, and lower cost care. EBBP
      programs have been studied for numerous adult conditions over the past decade,
      yet there have been no studies exploring the use of EBBP in pediatric conditions.
      Methods: This article explores the feasibility of EBBP for a relatively common,
      costly, pediatric surgical procedure: spinal fusion for adolescent idiopathic
      scoliosis. We begin with a review of successful EBBP programs in the United
      States. We then apply American College of Surgeons criteria for bundled payment
      episode selection to identify benefits and challenges of using EBBP for this
      condition. Results: We identify several features of pediatric spinal fusion that
      make it an attractive EBBP target: high variability in costs with multiple
      distinct targets for cost reduction, high variability in quality across
      hospitals, and proven methods for improvement via application of standardized,
      evidence based pathways. We find that challenges to EBBP may arise due to the
      relatively low incidence of the procedure, which limits overall savings to the
      health-care community. Conclusions: Our results suggest that spinal fusion for
      adolescent idiopathic scoliosis is an attractive pediatric target for EBBP, with
      potential benefits to patients, providers, health systems, and payers if
      limitations in procedure volume and administrative expense are overcome. The
      framework presented may also be useful for analyzing feasibility of EBBP for
      other pediatric conditions.

PMID- 30229166
TI  - Application of Conjoint Analysis to Improve Reliability of Dietician Consultation
      in Pediatric Celiac Disease.
AB  - Introduction: Celiac disease (CD) management involves lifelong adherence to a
      gluten-free diet, making the dietician a key member in CD care. However, our
      institution lacked a standardized process for dietary consultation in newly
      diagnosed CD. Methods: To understand provider CD care preferences, a 24-1
      fractional factorial conjoint analysis was performed. Attributes studied (2
      levels each) included type of initial follow-up gastroenterology (GI) provider,
      interval from diagnosis to follow-up, concurrence of initial dietary consultation
      with gastroenterology visit, and on-going follow-up GI provider. CD care was
      standardized in July 2014 to facilitate concurrent visits with the clinician and
      dietician during the same clinical session. Changes to mean time of dietary
      consultation and reliability of dietary consultation were monitored using an
      individual-control and G-control chart, respectively. Standard control chart
      rules were followed. Results: Conjoint analysis identified shorter time to
      initial follow-up visit and concurrent GI/dietician visits as more important
      attributes in newly diagnosed CD subjects' care. Types of follow-up provider
      during first or subsequent visits were identified as less important attributes.
      After initiation of a standardized follow-up process, a special cause was
      identified in December 2015 with a decrease in the mean time to dietary
      consultation from 30 to 20 days. In addition, standardized follow-up resulted in
      a more reliable process as evident by a special cause on the G-control chart in
      February 2015. Conclusion: Conjoint analysis identified attributes thought to be
      important in CD follow-up care. After redesign of our care process, a decrease in
      time to dietary consultation with improved reliability was observed.

PMID- 30229168
TI  - Deployment of a Second Victim Peer Support Program: A Replication Study.
AB  - Background: The second victim phenomenon occurs when health-care providers
      experience significant professional distress (compassion dissatisfaction,
      burnout, secondary traumatic stress) and psychological distress (shame, anxiety,
      and depression) as a result of medical errors or adverse patient outcomes. Few
      hospitals have institution-wide systems in place to assist employees through the
      recovery process. Methods: At Nationwide Children's Hospital (NCH), a peer-based
      support program called "YOU Matter" was executed and spread hospital-wide. The
      program emulated the framework and execution strategy designed by University of
      Missouri Health Care's (MUHC) "forYOU" Team. Strategic elements of the program's
      structure were reviewed and adapted for NCH with system-wide deployment and
      enhancement to include electronic peer support reporting. This article summarizes
      program implementation, management, and sustainment over the past 2 years.
      Results: By following University of Missouri Health Care's model, we successfully
      deployed an institution-wide second victim program. Since the November 2013
      initiation, we have documented 232 peer and 21 group encounters. High-risk
      clinical areas for second victimization at NCH included the emergency department
      (ED), pediatric intensive care unit (PICU), cardiothoracic intensive care unit
      (CTICU), and pharmacy department. Registered nurses (RNs) and licensed practical
      nurses (LPNs) have had the highest number of encounters necessitating second
      victim support (32%). Supported staff reported improved emotional state and
      improved return-to-work metrics. Conclusions: An organization's culture of
      patient safety can be enhanced by ensuring staff psychological safety. Programs
      like "YOU Matter" and the "forYOU" Team are essential building blocks to improve
      the overall safety culture and quality of care. Implementation of "YOU Matter" at
      NCH validates the MUHC program and demonstrates its generalizability to other
      health-care institutions.

PMID- 30229167
TI  - Effects of Skin-to-Skin Care on Late Preterm and Term Infants At-Risk for
      Neonatal Hypoglycemia.
AB  - Objective: The objective of this study was to evaluate the effects of prolonged
      skin-to-skin care (SSC) during blood glucose monitoring (12-24 hours) in late
      preterm and term infants at-risk for neonatal hypoglycemia (NH). Study design: We
      conducted a retrospective pre- and postintervention study. We compared late
      preterm and term infants at-risk for NH born in a 1-year period before the SSC
      intervention, May 1, 2013, to April 30, 2014 (pre-SSC) to at-risk infants born in
      the year following the implementation of SSC intervention, May 1, 2014, to April
      30, 2015 (post-SSC). Results: The number of hypoglycemia admissions to neonatal
      intensive care unit among at-risk infants for NH decreased significantly from
      8.1% pre-SSC period to 3.5% post-SSC period (P = 0.018). The number of infants
      receiving intravenous dextrose bolus in the newborn nursery also decreased
      significantly from 5.9% to 2.1% (P = 0.02). Number of infants discharged
      exclusively breastfeeding increased from 36.4% to 45.7%, although not
      statistically significant (P = 0.074). Conclusion: This SSC intervention, as
      implemented in our hospital, was associated with a significant decrease in
      newborn hypoglycemia admissions to neonatal intensive care unit. The SSC
      intervention was safe and feasible with no adverse events.

PMID- 30229170
TI  - Quality Improvement Leadership in Academic Children's Hospitals.

PMID- 30229169
TI  - Increasing Physical Exam Teaching on Family-Centered Rounds Utilizing a Web-Based
      Tool.
AB  - Introduction: Millennial trainees prefer innovative, multimodal education on
      topics including the physical exam (PE). Attendings inconsistently meet these
      needs on family-centered rounds. To enhance PE teaching, a Web site (PEToolkit)
      was created, but its use was infrequent. We aimed to increase PEToolkit use from
      2 to 5 page counts per week in 7 months. Methods: This quality improvement
      project took place at a large academic center in 1 Hospital Medicine team. Key
      drivers informed interventions, and an annotated run chart tracked progress. We
      tracked secondary measures, including changes in perception of teaching skill
      among attendings and resident-observed methods of PE teaching, through survey
      methodology. Results: Median page counts increased to 5 counts per week in 7
      months. The most impactful interventions included training senior residents to
      teach with the PEToolkit Web site and team feedback on Web site usage midweek.
      Survey responses from 37 attendings showed that those with more exposure to
      PEToolkit had increased self-perceived skill of PE teaching (P = 0.02). Survey
      responses from 52 residents showed that those on the intervention team reported
      more use of video for PE teaching (P < 0.001) and higher frequency of PE teaching
      (P = 0.02), compared with those on the nonintervention team. Conclusions: We
      increased PEToolkit Web site use during family-centered rounds, thereby
      emphasizing the importance of PE teaching in this setting in an innovative way.
      Engagement of learners, frequent feedback, and coaching should be considered when
      incorporating technology in teaching.

PMID- 30229172
TI  - Quality in Context: The Role of Social Determinants of Health in Pediatric
      Quality Improvement.

PMID- 30229171
TI  - Impact of a Successful Speaking Up Program on Health-Care Worker Hand Hygiene
      Behavior.
AB  - Background: Health-care worker (HCW) hand hygiene (HH) is the cornerstone of
      efforts to reduce hospital infections but remains low. Real-time mitigation of
      failures can increase process reliability to > 95% but has been challenging to
      implement for HH. Objective: To sustainably improve HCW HH to > 95%. Methods: A
      hospital-wide quality improvement initiative to improve HH was initiated in
      February 2012. HCW HH behavior was measured by covert direct observation
      utilizing multiple-trained HCW volunteers. HH compliance was defined as correct
      HH performed before and after contact with the patient or the patient's care
      area. Interventions focusing on leadership support, HCW knowledge, supply
      availability, and culture change were implemented using quality improvement
      science methodology. In February 2014, the hospital began the Speaking Up for
      Safety Program, which trained all HCWs to identify and mitigate HH failures at
      the moment of occurrence and addressed known barriers to speaking up. Results:
      Between January 1, 2012, and January 31, 2016, there were 30,514 HH observations,
      averaging 627 observations per month (9% attending physicians, 12% resident
      physicians, 46% nurses, 33% other HCW types). HCW HH gradually increased from 75%
      to > 90% by December 2014. After the Speaking Up for Safety Program, HCW HH has
      been > 95% for 20 months. Physician HH compliance has been above 90% for over a
      year. Conclusion: Creating a specific process for staff to speak up and prevent
      HH failures, as part of a multimodal improvement effort, can sustainably increase
      HCW HH above 95%.

PMID- 30229173
TI  - Utilizing Lean Principles to Improve Immunization Administration Efficiency in a
      Pediatric Mobile Clinic Program.
AB  - Introduction: Mobile clinics are vital health care delivery systems because they
      provide care to those who may not have access otherwise. Unfortunately, clinic
      flow on mobile clinics is often chaotic and inherently inefficient. Lean is a
      customer-centric methodology used in industries like health care to continuously
      improve processes by eliminating waste. The purpose of this project was to use
      lean principles to improve efficiency, as measured by total time spent receiving
      services, so that more underserved patients could receive needed immunizations.
      Methods: Using a certified lean expert, lean principles were applied to the
      mobile clinic program to uniformly organize the program, simplify registration
      processes, and standardize clinic procedures. Time study data were collected
      prospectively on a total of 309 patients for 2-week periods both before and after
      application of lean principles. Staff used a standardized time study form to
      record patient visit times. Pre- and postintervention data were analyzed using
      unpaired t tests and nonparametric Mann-Whitney tests as deemed appropriate.
      Results: Using lean principles significantly reduced total times spent for 1-, 2
      , and 4-children families. Wait times for 1- and 4-children families were also
      significantly decreased. Lastly, times spent on board the mobile clinic to
      receive immunizations for 1- and 3-children families were significantly
      decreased. Conclusion: Application of lean principles can improve efficiency by
      decreasing total time spent for patients receiving vaccine services on pediatric
      mobile clinics.

PMID- 30229174
TI  - Implementation of the Asthma Control Test in a Large Primary Care Network.
AB  - Introduction: Achieving control in asthma is a primary goal of pediatric care,
      and assessing the degree of control is a principal step in management. The
      purpose of this quality improvement project was to implement the Asthma Control
      Test (ACT) and the Childhood Asthma Control Test (C-ACT) in a large primary care
      network as a means to reliably and consistently assess asthma control at all
      visit types. Methods: A prospective design was used to measure provider
      documentation of the ACT or C-ACT. Patients (or caregivers) 4 years of age or
      older with a known diagnosis of asthma were administered the ACT (ages 12 and
      older) or the C-ACT (ages, 4-11). The quality improvement project, which involved
      multiple interventions, took place at 11 centers of the Primary Care Network of
      Nationwide Children's Hospital from November 2013 to December 2014. A goal was
      set for a 70% completion rate of the ACT/C-ACT at any visit type for patients 4
      years of age or older with asthma. Results: Six months after the introduction of
      the questionnaires, the 70% completion rate was reached. Rates of ACT/C-ACT
      completion have consistently exceeded 70% through December 2016. Conclusions: We
      demonstrated that the ACT/C-ACT can be integrated into a busy primary care
      network. It is imperative to work toward better asthma care; consistent
      assessment of asthma control can be the critical first step.

PMID- 30229175
TI  - Integrating a Geneticist in a Multidisciplinary Clinic for Down Syndrome
      Increases Commitment to Genetic Counseling.
AB  - Background: Although most physicians and genetic professionals are familiar with
      Down syndrome, many families do not have experience with Down syndrome before
      having a child diagnosed. The American Academy of Pediatrics has specific
      recommendations for genetic counseling and chromosome analysis for Down syndrome.
      Local Problem: The literature indicates that adherence to completion of
      appropriately timed genetic counseling is low at 31%. This study was initiated to
      determine our adherence rates and to improve if needed. Methods: In the Down
      syndrome clinic at Nationwide Children's Hospital, a subspecialty clinic in the
      Division of Developmental and Behavioral Pediatrics, a genetic counselor was on
      call but did not routinely attend. The intervention consisted of
      multidisciplinary care with the presence of a clinical geneticist. Statistical
      Process Control Charts and Fisher's exact test were used to determine the impact
      of the intervention. Results: Our baseline rate of adherence to genetic
      counseling was similar to previous publications. Direct genetics involvement in
      the Down syndrome clinic in place of an on-call genetic counselor led to
      significant improvement in adherence to genetic counseling recommendations over a
      6-month period from 35% to 62%, P < 0.001 and sustained for 6 months. Postclinic
      adherence rates and subanalyses by age showed similar results. The final
      postvisit adherence rate of 89% in February 2017 demonstrates continued
      improvement. Geneticist involvement allowed chromosome reports uploading and
      karyotype listing in electronic medical records. Implications and Lessons
      Learned: Genetic counseling in newborns with Down syndrome is important, yet was
      often not received at Nationwide Children's Hospital before this study.
      Integrating a geneticist resulted in improvement. Implementing similar models at
      other institutions can ensure that the correct genetic testing is completed,
      results documented and families counseled appropriately.

PMID- 30229176
TI  - Development of Pediatric Emergency Protocols and Communication Plans in Pediatric
      Radiation Oncology: Multidisciplinary Core Competencies.
AB  - Radiation therapy is an essential component of treatment for many pediatric
      cancers, yet the cost of maintaining a radiation facility at a dedicated
      pediatric center is often prohibitive. As a result, adult facilities treat
      pediatric patients where preparation for a pediatric emergency may be inadequate.
      The purpose of this quality improvement project was to develop a
      multidisciplinary emergency preparedness plan for a collaborative pediatric
      radiation oncology program at an adult community hospital with its partnering
      academic children's hospital. Using a cyclical process involving
      multidisciplinary collaboration that combines policy development, preparation,
      and team-building, the authors created the protocols and processes that would
      support the stabilization of a pediatric emergency and facilitate transfer to the
      partnering children's hospital. Further development of a communication plan
      outlines the flow of patient information through the multidisciplinary team
      during these transitions of care. Areas for future work include quantitative
      outcome measures to determine the effectiveness of the policies and procedures
      developed to prepare staff for pediatric emergencies.

PMID- 30229177
TI  - Improving Inpatient Asthma Management: The Implementation and Evaluation of a
      Pediatric Asthma Clinical Pathway.
AB  - Introduction: Asthma exacerbations are a leading cause of pediatric
      hospitalizations. Despite national guidelines, variability exists in the use and
      dosing of bronchodilators, oxygen management, and respiratory assessments of
      patients. We aimed to implement an inpatient Asthma Clinical Pathway (Pathway) to
      standardize care and reduce length of stay (LOS). Methods: A respiratory therapy
      driven Pathway was designed for inpatient asthma management. The Pathway included
      standardized respiratory therapy assessments, bronchodilator dosing, and
      protocols for progression and clinical worsening. We monitored key process
      measures. Patients admitted to the Pathway during pilot implementation (March to
      December 2011) were compared retrospectively with a "Usual Care" cohort admitted
      during the same period. We compared average LOS, average billed charges per
      hospitalization (charges), and 30-day readmissions between groups. Statistical
      process control charts were utilized to analyze LOS and charges for all asthma
      admissions following Pathway implementation (March 2011 to September 2016).
      Readmissions and Pathway removals were balancing measures. Results: During pilot,
      Pathway patients (n = 153) compared with "Usual Care" patients (n = 166) had
      shorter LOS (0.95 versus 1.86 days; P < 0.001) and lower charges ($7,413 versus
      $11,078; P < 0.001). Readmission rates were not significantly different between
      groups. LOS for all asthma admissions (n = 3,429) decreased from 2.30 to 1.44
      days (P < 0.001) following Pathway implementation. Charges remained stable. The
      readmission rate (per 100 discharges) for all asthma was 2.42 and not
      significantly different between Pathway and non-Pathway groups. Conclusions:
      Pathway implementation reduced LOS and stabilized charges while not increasing
      readmission rates. The Pathway facilitated sustainable widely adopted
      improvements in asthma care.

PMID- 30229179
TI  - Implementation of an Outcome Measure in Pediatric Behavioral Health: A Process
      Improvement Initiative.
AB  - Introduction: Efforts to monitor outcomes in pediatric behavioral health are
      becoming a quality, financial, and regulatory imperative. The implementation of a
      broad-based measure to assess patient functioning at the start of pediatric
      psychology services, as well as at subsequent visits, has not been demonstrated.
      This article describes the systematic implementation of a measure of health
      related quality of life (HRQOL) to assess functional impairment across an entire
      clinic population using quality improvement science and methodologies. Methods:
      The Pediatric Quality of Life Inventory Generic Core 4.0 (PedsQL) was
      administered at initial and subsequent visits for all patients seeking treatment
      at a large, tertiary care pediatric psychology clinic in an academic pediatric
      medical center (Nationwide Children's Hospital, Columbus, Ohio). The goal of this
      project was to design a process change to support a 90% completion rate of this
      measurement tool by all clinicians. Results: Within 16 months, the completion
      rate of the PedsQL increased from a baseline of 39% to the identified goal of
      90%. This process change was within control limits (over 80%) for over 12 months.
      Conclusion: This study demonstrates the implementation of a systematic process
      for collection of outcome measures in a pediatric behavioral health care setting.
      Successful administration of an outcome measure at multiple time points during
      the care of children and adolescents in a large psychology clinic can allow for
      quantitative assessment of treatment progress and identify a pathway for
      administration of additional measures.

PMID- 30229178
TI  - Noncompliance to a Postoperative Algorithm Using Feeding Readiness Assessments
      Prolonged Length of Stay at a Pediatric Heart Institute.
AB  - Introduction: Variable compliance to postoperative feeding algorithms after
      pediatric cardiac surgery may be associated with suboptimal growth, decreased
      parental satisfaction, and prolonged hospital length of stay (LOS). Our heart
      center performed an audit of compliance to a previously introduced postoperative
      feeding algorithm to guide quality improvement efforts. We hypothesized that
      algorithm noncompliance would be associated with increased LOS. Methods: We
      retrospectively identified children <= 3 months admitted for their first cardiac
      surgery between January 1, 2015 and December 31, 2016. The algorithm uses
      objective oral feeding readiness assessments (FRA). At the end of a predefined
      evaluation period, a "sentinel" FRA score is assigned. The sentinel FRA and FRA
      trend guide decisions to pursue gastrostomy tube (GT) or oral-only feeds. Among
      those who reached the sentinel FRA, we defined compliance as <= 3 days before
      pursuing GT or oral-only feeds once indicated by the algorithm. Results: Sixty
      nine patients were included. Forty-nine complied with the algorithm (71%), and 45
      received GT (65.2%). Noncompliers had significantly longer LOS (34 versus 25
      days; P = 0.01). Among GT recipients, noncompliers waited 6 additional days for a
      GT compared with compliers (P <= 0.001). Subjective decisions to extend oral
      feeding trials or await results of a swallow study were associated with algorithm
      noncompliance. Conclusions: This audit of compliance to a feeding algorithm after
      pediatric cardiac surgery highlighted variability of practice, including relying
      on subjective appraisals of feeding skills over objective FRAs. This variability
      was associated with increased LOS and can be hypothesis-generating for future
      quality improvement efforts.

PMID- 30229181
TI  - SAFEST: Use of a Rubric to Teach Safety Reporting to Pediatric House Officers.
AB  - Background: Among the many modalities of error detection in academic pediatric
      hospitals, patient safety reporting is an important component, particularly for
      unexpected events. Residents recognize the importance of reporting but cite some
      barriers to doing so. A rubric was developed to guide resident reporting and
      streamline information gathering in patient safety reports. The rubric used the
      acronym SAFEST as a reminder to include 6 key elements:1. Staff involved in the
      incident.2. Actual event description.3. Follow-up initiated.4. Effect on
      patient.5. Standard of care described.6. To-do/suggestions for improvement.
      Objectives: This study was designed to determine if the addition of this
      educational rubric into a standard quality improvement curriculum improves the
      consistency of information documented in patient safety reports as a subset of a
      larger quality improvement project aimed at improving safety reporting. Methods:
      A team of faculty members analyzed individual resident error reports for
      adherence to the 6 tenets of the SAFEST mnemonic. Results: From April to October
      of 2014, 2015, and 2016, a convenience sample of 131, 110, and 132 reports,
      respectively, were extracted and analyzed. For the rates of reporting "staff
      involved" and "standard of care," the differences over time were significant,
      both with P values < 0.001. After training, residents were 2.2 times more likely
      to report on the "staff involved" in the error and 1.8 times more likely to
      report the "standard of care." Discussion: These results describe successful
      education on a rubric designed to improve the content of patient safety reports.

PMID- 30229180
TI  - WE CARE 4 KIDS: Use of a Rounding Tool in the Pediatric Intensive Care Unit.
AB  - Objective: To implement a daily rounding tool in a pediatric intensive care unit
      (PICU) to improve the discussion performance of identified clinical elements. We
      hypothesized that a semi-structured rounding tool created by a multidisciplinary
      team would be successfully implemented and sustained in the PICU. Patients and
      Methods: A pre-post interventional study was conducted in a multidisciplinary
      medical-surgical PICU. Baseline data collection of undisclosed clinical elements
      was performed by covert observers, which resulted in the development of a
      comprehensive, nurse-driven rounding checklist. Frequencies of pre- and
      postintervention metrics were assessed after implementation, and sustainability
      was assessed at 5 years. Results: Six months after implementation, 70% (7/10) of
      checklist elements demonstrated significant improvement. Five years after
      implementation, 172 of a possible 222 (74%) checklists were collected. Eighty
      percentage (8/10) of the measures sustained discussion frequency after 5 years of
      use. Nursing presence significantly improved at year 5 compared with the
      preimplementation period. Nursing satisfaction surveys distributed at year 5
      showed that the rounding tool was useful and nurses were confident in
      understanding care plans at the end of rounds. Ninety-eight percentage of
      checklists revealed discrete transcription of qualitative daily goals.
      Conclusions: A semi-structured rounding tool created by a multidisciplinary team
      was successfully implemented, and performance was sustained at 5 years. This
      initiative led to improved bedside nursing presence during patient care rounds.

PMID- 30229182
TI  - Reducing Antibiotic Use in Respiratory Syncytial Virus-A Quality Improvement
      Approach to Antimicrobial Stewardship.
AB  - Objective: The increased incidence of multidrug-resistant organisms is associated
      with increased morbidity, mortality, hospital length of stay, and cost. Estimates
      show that up to 50% of antimicrobial use is inappropriate. This initiative
      focuses on inappropriate use of antibiotics in respiratory syncytial virus (RSV)
      infections. This virus is the most common cause of bronchiolitis during
      childhood. Methods: Baseline data from the 2011-2012 RSV season showed that 56.2%
      of our RSV-positive patients received antibiotics. To decrease inappropriate
      antibiotic use in RSV infections, we established an antimicrobial stewardship
      program (ASP). This process improvement initiative aimed to decrease exposure to
      antibiotics and days of antibiotic therapy per 1,000 patient days (DOT/1000PD) in
      hospitalized RSV-positive patients by 25%. Key drivers included building health
      care knowledge, proactive interventions using prospective audit and feedback,
      emergency department engagement, and performance dashboards. Results: We included
      a total of 290 children in the final analysis. After full implementation of the
      ASP, there was a significant reduction of antibiotic exposure from 56.2% to 30.9%
      (P < 0.001), an absolute reduction of 25% and a relative reduction of 45%. There
      was also a significant decrease in DOT/1000PD from 432.7 to 268.1 days (P =
      0.017). This change represents a reduction of 164.6 DOT/1000PD from baseline
      after full ASP implementation. Conclusion: Despite the lack of a unified
      hospitalist group in our institution, we were successful in reducing
      inappropriate antibiotic use by focusing on standardizing care among different
      private pediatricians in the community. A multifaceted strategy and well-designed
      quality improvement methodology led to a sustained reduction in antibiotic use.

PMID- 30229183
TI  - Reducing Blood Testing in Pediatric Patients after Heart Surgery: Proving
      Sustainability.
AB  - Introduction: Frequent blood testing increases risk of iatrogenic anemia,
      infection, and blood transfusion. This study describes 3 years of sustained blood
      testing reduction from a quality improvement (QI) initiative which began in 2011.
      Methods: The cohort consisted of postop children whose surgery had a Risk
      Adjustment for Congenital Heart Surgery (RACHS) classification consecutively
      admitted to a tertiary Cardiac Intensive Care Unit. Data were collected for a
      2010 preintervention, 2011 intervention, and 2012-13 postintervention periods,
      tabulating common laboratory studies per patient (labs/pt) and adjusted for
      length of stay (labs/pt/d). The QI initiative eliminated standing laboratory
      orders and changed to testing based on individualized patient condition. Adverse
      outcomes data were collected including reintubation, central line-associated
      bloodstream infections and hospital mortality. Safety was measured by the number
      of abnormal laboratory studies, electrolyte replacements, code blue events, and
      arrhythmias. Results: A total of 1169 patients were enrolled (303
      preintervention, 315 intervention, and 551 postintervention periods). The number
      of labs/pt after the QI intervention was sustained (38 vs. 23 vs. 23) and
      labs/pt/d (15 vs. 11 vs. 10). The postintervention group had greater surgical
      complexity (P = 0.002), were significantly younger (P = 0.002) and smaller (P =
      0.008). Children with RACHS 3-4 classification in the postintervention phase had
      significant increased risk of reintubation and arrhythmias. Conclusions: After
      the implementation of a QI initiative, blood testing was reduced and sustained in
      young, complex children after heart surgery. This may or may not have contributed
      to greater reintubation and arrhythmias among patients with RACHS 3-4 category
      procedures.

PMID- 30229184
TI  - Improving Human Papilloma Virus Vaccination Rates: Quality Improvement.
AB  - Background: Human papilloma virus (HPV) is a sexually transmitted infection with
      a national prevalence of greater than 70 million. Most infections are among
      persons 15-24 years of age. The HPV vaccine has nearly 100% efficacy when
      administered before natural exposure. However, national vaccination rates remain
      less than 50%. Our objective was to improve the rate of initiation of the HPV
      vaccination series in a resident teaching practice. Methods: We used the Plan Do
      Study Act methodology for quality improvement. Eligible patients included
      children 9 through 13 years of age who presented to a general pediatric clinic.
      We established baseline data by reviewing HPV immunization rates taken from a
      convenience sample of <=20 patients per month over 7 months. A key driver diagram
      guided interventions including resident communication, nursing staff education,
      family knowledge, and an electronic medical record prompt beginning at age 9.
      Using standard run chart rules, we plotted monthly postintervention vaccination
      rates over 7 months of data collection. Results: Baseline data included 136
      patients age 9-13. Run chart monitoring revealed an increase in our HPV
      vaccination rate from 53% at baseline to 62% by October 2015. Additionally, we
      observed a statistically significant increase in mean vaccination rates from 50%
      to 69% (odds ratio 2.071; P = 0.0042). We noted an increase in vaccination rates
      after resident education initiatives and after implementation of an electronic
      medical record prompt. Conclusions: Simple and practical interventions involving
      residents led to a marked increase in HPV vaccination in our patient population.

PMID- 30229185
TI  - Increasing Patient Portal Activation in a Pediatric Subspecialty Clinic.
AB  - Background: Online patient portals are not widely used, despite their advantages
      for efficient communication, especially for patients with chronic conditions. A
      hospital-based group practice of Developmental-Behavioral Pediatricians initiated
      this quality improvement (QI) project with a goal to increase the percentage of
      patients with an active MyChart (Epic Systems Corporation's patient portal)
      account and ultimately improve efficiency of communication between families and
      clinical staff. Methods: Using QI methodology, we identified staff commitment,
      workflow issues, and family awareness as gaps and implemented progressive Plan,
      Do, Study, Act cycles aimed at developing standard processes for activating
      families on MyChart. We tracked our project measures with statistical process
      control methodology and sustained our progress with improving awareness and
      regular feedback. Results: Patient portal activations increased from 1.8% to 30%
      in a 6-month time period. Highly successful interventions included development
      and implementation of a standard process for activation, staff education to
      ensure comfort and commitment, having families opt out instead of opt in, and
      completed activation of accounts before families leaving clinic. Conclusions:
      Patient portal activation can be significantly increased through systematic
      application of QI methodology to address staff training and workflow in a busy
      subspecialty clinic. Engagement of operations staff and completion of the
      activation process while the family is still in clinic seemed to be effective in
      getting families activated in MyChart. It is possible to improve patient portal
      activation with minimal impact to workflow.

PMID- 30229186
TI  - Using Length of Stay to Understand Patient Flow for Pediatric Inpatients.
AB  - Objectives: Develop and test a new metric to assess meaningful variability in
      inpatient flow. Methods: Using the pediatric administrative dataset, Pediatric
      Health Information System, that quantifies the length of stay (LOS) in hours, all
      inpatient and observation encounters with 21 common diagnoses were included from
      the calendar year 2013 in 38 pediatric hospitals. Two mutually exclusive
      composite groups based on diagnosis and presence or absence of an ICU
      hospitalization termed Acute Care Composite (ACC) and ICU Composite (ICUC),
      respectively, were created. These composites consisted of an observed-to-expected
      (O/E) LOS as well as an excess LOS percentage (ie, the percent of day beyond
      expected). Seven-day all-cause risk-adjusted rehospitalizations was used as a
      balancing measure. The combination of the ACC, the ICUC, and the
      rehospitalization measures forms this new metric. Results: The diagnosis groups
      in the ACC and the ICUC included 113,768 and 38,400 hospitalizations,
      respectively. The ACC had a median O/E LOS of 1.0, a median excess LOS percentage
      of 23.9% and a rehospitalization rate of 1.7%. The ICUC had a median O/E LOS of
      1.1, a median excess LOS percentage of 32.3%, and rehospitalization rate of 4.9%.
      There was no relationship of O/E LOS and rehospitalization for either ACC or
      ICUC. Conclusions: This metric shows variation among hospitals and could allow a
      pediatric hospital to assess the performance of inpatient flow.

PMID- 30229187
TI  - A Quality Improvement Collaborative for Pediatric Sepsis: Lessons Learned.
AB  - Background: Sepsis is a leading cause of morbidity and mortality in children
      worldwide. Barriers exist for timely recognition and management in emergency care
      settings. This 1-year quality improvement collaborative sought to reduce
      mortality from sepsis. Methods: Fifteen hospitals participated initially. We
      included children with a spectrum of illness from sepsis to septic shock. The
      intervention bundle focused on recognition, escalation of care, and the first
      hour of resuscitation. We conducted monthly learning sessions and disseminated
      data reports of site-specific and aggregated metrics to drive rapid cycle
      improvement. Results: Seven sites contributed enough data to be analyzed. Of the
      1,173 pediatric patients in the total cohort, 506 presented with severe
      sepsis/septic shock. Quarterly data demonstrated a mean improvement in initial
      clinical assessment from 46% to 60% (P < 0.001) and in adherence to the
      administration of first fluid bolus within 15 minutes from 38% to 46% (P <
      0.015). There was no statistically significant improvement in other process
      metrics. There was no statistically significant improvement in mortality for the
      total cohort (sepsis to septic shock) or either of the subgroups in either 3- or
      30-day mortality. Conclusions: A quality improvement collaborative focused on
      improving timely recognition and management of pediatric sepsis to septic shock
      led to some process improvements but did not show improvement in mortality.
      Future national efforts should standardize definitions and processes of care for
      sepsis to septic shock, including the identification of a "time zero" for
      measuring the timeliness of treatment.

PMID- 30229188
TI  - A Quality Improvement Initiative to Increase and Sustain Influenza Vaccination
      Rates in Pediatric Oncology and Stem Cell Transplant Patients.
AB  - Introduction: Influenza vaccination of pediatric oncology and stem cell
      transplant (SCT) patients is crucial due to high risk of complications. Achieving
      high vaccination rates to prevent illness is often limited by competing demands
      and intensive treatment. A quality improvement (QI) initiative beginning
      influenza season 2012-2013 aimed to achieve and sustain high vaccination rates in
      active patients > 6 months of age, receiving cancer therapy or SCT within 6
      months before or at any time during the season, and > 100 days after allogeneic
      SCT. Methods: We identified key drivers and barriers to success from an initially
      developed vaccination process that proved to be burdensome. Change ideas were
      implemented through multiple tests of change during the QI initiative. Iterations
      within and across 4 subsequent seasons included patient identification through
      chemotherapy orders, provider education, incorporating vaccination into routine
      work-flow, continuous data analysis and feedback, and use of new reporting
      technology. Results: Initial vaccination rates were < 70%, increasing to 89%
      after the QI initiative began and subsequently sustained between 85% and 90%.
      Active patients were significantly more likely to be vaccinated during the
      initiative (odds ratio, 3.7; 95% CI, 2.9-4.6) as compared with the first 2
      seasons. Conclusions: High influenza vaccination rates can be achieved and
      maintained in a pediatric oncology/SCT population using strategies that correctly
      identify patients at highest risk and minimize process burden.

PMID- 30229189
TI  - Reducing Interdisciplinary Communication Failures Through Secure Text Messaging:
      A Quality Improvement Project.
AB  - Introduction: Interdisciplinary communication failures contribute to medical
      mistakes and adverse events. At our institution, provider communication
      previously occurred through unidirectional pager systems. We utilized quality
      improvement methodology to (1) implement a secure text messaging system for
      providers on a pediatric ward and (2) evaluate its impact on communication
      failures. We aimed to reduce potential communication failures between providers
      by > 25% within 1 month. Methods: Implementation of secure text messaging
      occurred via Plan-Do-Study-Act cycles focused on education, feedback, and
      electronic health record interventions. We collected pager data before
      implementation and both pager and secure text messaging data after intervention.
      Potential communication failures were identified a priori through manual review
      of the messaging data to capture lack of closed-loop communication. A run chart
      was used to track daily potential communication failures and total communication
      volumes. Results: Before implementation of secure text messaging, the median
      daily potential communication failure rate was 5.5%. Usage of secure text
      messaging increased after implementation, representing 3.5 of 7.2 communications
      per patient-day. Paging communications decreased from 4.2 to 3.7 per patient-day.
      Potential communication failures decreased to a median daily rate of 2.2%,
      representing a 59% reduction in communication failures. Conclusion:
      Implementation of secure text messaging using quality improvement methods
      resulted in a significant reduction in potential communication failures between
      residents and nurses. Future interventions will be aimed at maintaining and
      augmenting providers' use of secure text messaging to ensure the potential for
      communication failure remains low.

PMID- 30229190
TI  - Impact of a Daily PICU Rounding Checklist on Urinary Catheter Utilization and
      Infection.
AB  - Introduction: In critically ill children, inappropriate urinary catheter (UC)
      utilization is associated with increased morbidity, including catheter-associated
      urinary tract infections (CAUTIs). Checklists are effective for reducing medical
      errors, but there is little data on their impact on device utilization in
      pediatric critical care. In this study, we evaluated UC utilization trends and
      CAUTI rate after implementing a daily rounding checklist. Methods: A
      retrospective review of our checklist database from 2006 through 2016 was
      performed. The study setting was a 36-bed pediatric intensive care unit in a
      quaternary-care pediatric hospital. Interventions included the "Daily QI
      Checklist" in 2006, ongoing education regarding device necessity, and a CAUTI
      prevention bundle in 2013. UC utilization and duration were assessed via auto
      correlated time series models and Cochran-Armitage tests for trend. Changes in
      CAUTI rate were assessed via Poisson regression. Results: UC utilization
      decreased from 30% of patient-days in 2006 to 18% in 2016 (P < 0.0001, Cochran
      Armitage trend test), while duration of UC use (median, 2.0 days; interquartile
      range, 1-4) did not change over time (P = 0.18). CAUTI rate declined from
      9.49/1,000 UC-days in 2009 to 1.04 in 2016 (P = 0.0047). Conclusions:
      Implementation of the checklist coincided with a sustained 40% reduction in UC
      utilization. The trend may be explained by a combination of more appropriate
      selection of patients for catheterization and improved timeliness of UC
      discontinuation. We also observed an 89% decline in CAUTI rate that occurred
      after stabilization of UC utilization. These findings underscore the potential
      impact of a checklist on incorporating best practices into daily care of
      critically ill children.

PMID- 30229191
TI  - Shortened Taper Duration after Implementation of a Standardized Protocol for
      Iatrogenic Benzodiazepine and Opioid Withdrawal in Pediatric Patients: Results of
      a Cohort Study.
AB  - Introduction: Methadone and lorazepam prescribing discrepancies for the use of
      iatrogenic withdrawal were observed among providers. A standardized pharmacist
      managed methadone and lorazepam taper protocol was implemented at a pediatric
      tertiary care facility with the aim to reduce the length of taper for patients
      with iatrogenic withdrawal. Methods: A multidisciplinary team of nurses,
      pharmacists, and physicians reviewed the current literature, then developed and
      implemented a standardized withdrawal taper protocol. Outcomes were compared with
      a retrospective control group using past prescribing practices. The primary
      endpoint was the length of methadone and/or lorazepam taper. Secondary endpoints
      included evaluation for significant differences between the control and
      standardized protocol groups regarding additional breakthrough withdrawal
      medications, pediatric intensive care unit (PICU) and hospital length of stay. We
      also evaluated provider satisfaction with the protocol. Results: The standardized
      protocol group included 25 patients who received methadone and/or lorazepam
      taper. A retrospective control group contained 24 patients. Median methadone
      taper length before protocol implementation was 9.5 days with an interquartile
      range (IQR) of 5.5-14.5 days; after protocol implementation, it was 6.0 (IQR, 3.0
      9.0) days (P = 0.0145). Median lorazepam taper length before protocol
      implementation was 13.0 (IQR, 8.0-18.0) days; after protocol implementation, it
      was 6.0 (4.0-7.0) days (P = 0.0006). A statistical difference between PICU length
      of stay, hospital length of stay, or the number of additional medications for
      breakthrough withdrawal was not found. Conclusions: The use of a standardized
      withdrawal protocol resulted in shorter taper duration for both the methadone and
      lorazepam groups. There was no difference in PICU or hospital length of stay.

PMID- 30229192
TI  - Evaluating the Impact of a Feeding Protocol in Neonates before and after
      Biventricular Cardiac Surgery.
AB  - Introduction: Feeding difficulties and malnutrition are important challenges when
      caring for newborns with critical congenital heart disease (CCHD) without clear
      available guidelines for providers. This study describes the utilization of a
      feeding protocol with the focus on standardization, feeding modality, and total
      parenteral nutrition (TPN) utilization postoperatively. Methods: Patients
      included neonates with CCHD undergoing complex biventricular repair using
      cardiopulmonary bypass. Data were collected in 2013 preintervention and from 2015
      to 2017 postintervention. The feeding protocol outlined guidelines for and
      postoperative use of TPN. Adverse outcomes data included rates of central line
      associated bloodstream infections, necrotizing enterocolitis, chylothorax, and
      vocal cord dysfunction. Balance outcomes measured were weight for age Z-score at
      discharge, number of abdominal radiographs obtained, readmission within 90 days,
      and central venous line utilization. Results: We included a total of 121
      neonates: 49 in the preintervention group and 72 in the postintervention group.
      The protocol standardized feeding practices in CCHD neonates undergoing surgery
      with improved compliance from 70% early in the study period to 90% at the end of
      the study. Infants were fed enterally more preoperatively (86% versus 67%; P =
      0.023), reached a fluid goal sooner (63 hours versus 72 hours; P = 0.035), and
      postoperative duration of TPN usage was significantly shorter in the
      postintervention period (48 hours versus 62 hours; P = 0.041) with no increase in
      adverse outcome events or unintended consequences. Conclusions: By implementing a
      feeding protocol, we reduced practice variation among providers, increased the
      number of patients fed enterally preoperatively and reduced postoperative use of
      TPN without increased complications.

PMID- 30229194
TI  - Improvement Science Takes Advantage of Methods beyond the Randomized Controlled
      Trial.

PMID- 30229195
TI  - Improving Wait Time for Patients in a Pediatric Echocardiography Laboratory - a
      Quality Improvement Project.
AB  - Background: Prolonged wait times for echocardiograms in the outpatient pediatric
      cardiology clinic led to patient and provider dissatisfaction at our institution.
      The aims of this project were to measure our baseline performance with regard to
      echocardiogram wait time (EWT), to implement a formal quality improvement (QI)
      program to improve EWT, and to measure the impact of QI on EWT. Methods: A QI
      team was formed comprising of cardiologists (A.P., T.S.), sonographer (A.W.), and
      QI mentor (J.M.). EWT was defined as time in minutes from initiation of the order
      in the electronic medical record to start of the echocardiogram. Goal EWT was set
      as <= 20 minutes for 90% patients. Flowcharts were created after process
      observation to identify sources of potential delay contributing to EWT. QI
      methodology such as driver diagrams were utilized to identify interventions,
      which were then implemented and studied as Plan-Do-Study-Act cycles. Results:
      Sequential interventions included early start time, huddles involving clinic and
      echo laboratory staff, patient tracking system, and repurposing of a clinic room
      for echo. EWT was tracked for 840 patients. Mean EWT was 22.5 +/- 17.5 minutes at
      baseline and decreased to 15.3 +/- 7.8 minutes postintervention (P < 0.001).
      Postintervention, 81% of the patients waited < 20 minutes for their echo, and 98%
      patients waited < 30 minutes, compared with baseline numbers of 62% and 76%,
      respectively (P < 0.001). Conclusions: We were able to utilize QI methodology to
      derive interventions and track changes, resulting in quantifiable improvement in
      EWT in a busy pediatric echo laboratory.

PMID- 30229193
TI  - Using a Pediatric Trigger Tool to Estimate Total Harm Burden Hospital-acquired
      Conditions Represent.
AB  - Introduction: To improve patient safety, the Centers for Medicare & Medicaid
      Services (CMS) has promoted systematically measuring and reporting harm due to
      patient care. The CMS's Partnership for Patients program identified 9 hospital
      acquired conditions (HACs) for reduction, to make care safer, more reliable, and
      less costly. However, the proportion of inpatient pediatric harm represented by
      these HACs is unknown. Methods: We conducted a retrospective review of 240 harms
      previously identified using the Pediatric All-Cause Harm Measurement Tool, a
      trigger tool that is applied to medical records to comprehensively identify
      harms. The original sample included 600 randomly selected patients from 6
      children's hospitals in February 2012. Patients with rehabilitation, obstetric,
      newborn nursery, and psychiatric admissions were excluded. The 240 identified
      harms were classified as a HAC if the event description potentially met the
      definition of 1 of the 9 CMS-defined HACs. HAC assessment was performed
      independently by 2 coauthors and compared using Cohen's Kappa. Results: Two
      hundred forty harms across 6 children's hospitals were identified in February
      2012 using a pediatric global trigger tool. Agreement between the coauthors on
      HAC classification was high (Kappa = 0.77). After reconciling differences, of the
      240 identified harms, 58 (24.2%; 95% confidence interval: 9.1-31.7%) were
      classified as a CMS-defined HAC. Conclusions: One-fourth of all harms detected by
      a pediatric-specific trigger tool are represented by HACs. Although substantial
      effort is focused on identifying and minimizing HACs, to better understand and
      ultimately mitigate harm, more comprehensive harm identification and
      quantification may be needed to address events unidentified using this approach.

PMID- 30229196
TI  - Assessing Barriers to Uveitis Screening in Patients with Juvenile Idiopathic
      Arthritis Through Semi-Structured Interviews.
AB  - Introduction: Uveitis is a significant complication in patients with juvenile
      idiopathic arthritis (JIA) and can be asymptomatic until vision loss develops.
      Published guidelines recommend uveitis screening eye examinations every 3-12
      months depending on multiple factors, but no literature evaluates adherence with
      and barriers to obtaining these screening eye examinations. This study assesses
      barriers in nonadherent patients to establish key drivers for future
      interventions. Methods: We identified patients with JIA who were nonadherent with
      uveitis screening guidelines through the electronic medical record (EMR). A
      rheumatologist conducted semistructured interviews with the patients or guardians
      regarding the patients' most recent eye examinations, knowledge of the screening
      frequency, and barriers to completing the eye examinations. The results were
      qualitatively analyzed to determine any categorical variables present. Results:
      Ninety-two patients were identified as nonadherent, and the rheumatologist
      interviewed 45 patients or guardians. Categories identified following the
      interviews were system problems, access to care issues, and knowledge deficits.
      The largest category identified was system problems that included most recent eye
      examination not being in the EMR, the wrong eye provider identified in the EMR or
      difficulty with scheduling eye appointments. Conclusions: This qualitative study
      identified categories of barriers to obtaining screening eye examinations in
      patients with JIA. Identification of these barriers will facilitate the
      development of a specific aim and key driver diagram to guide future quality
      improvement interventions.

PMID- 30229197
TI  - A Saturated Approach to the Four-Phase, Brain-Based Simulation Framework for
      TeamSTEPPS(r) in a Pediatric Medicine Unit.
AB  - Introduction: Although many organizations have reported successful outcomes as a
      result of Team Strategies and Tools to Enhance Performance and Patient Safety
      (TeamSTEPPS), implementation can be challenging, with its share of administrative
      obstacles and lack of research that shows observable change in practice. Methods:
      This quantitative, pretest/posttest design pilot research used a combination of
      classroom simulation-based instruction and in situ simulation in a Pediatrics
      department in an urban academic center. All personnel with direct patient care
      responsibilities (n = 547) were trained in TeamSTEPPS in an 8-week period.
      TeamSTEPPS course knowledge scores were compared pretraining to posttraining
      using the Wilcoxon rank-sum test. The performance of two-day and overnight shift
      teams, pre- and postintervention was assessed using the TeamSTEPPS Team
      Performance Observation Tool. Results: TeamSTEPPS course knowledge improved from
      the beginning of the course to completion with median scores of 16 and 19,
      respectively (P < 0.001). Both day and evening postintervention groups
      demonstrated greater team performance scores than their control counterparts.
      Specifically, postintervention day shift team showed the greatest improvement and
      demonstrated more TeamSTEPPS behaviors. Conclusion: This pilot study involving 1
      department in an urban hospital showed that TeamSTEPPS knowledge and performance
      could be improved to increase patient safety and reduce medical errors. However,
      teams need to be trained within a shorter period so they can apply a shared-model
      of teamwork and communication. Leaders and educators throughout the department
      must also reinforce the behaviors and include them in every education
      intervention.

PMID- 30229198
TI  - A Retrospective Review of a Bed-mounted Projection System for Managing Pediatric
      Preoperative Anxiety.
AB  - Introduction: Most children undergoing anesthesia experience significant
      preoperative anxiety. We developed a bedside entertainment and relaxation theater
      (BERT) as an alternative to midazolam for appropriate patients undergoing
      anesthesia. The primary aim of this study was to determine if BERT was as
      effective as midazolam in producing cooperative patients at anesthesia induction.
      Secondary aims reviewed patient emotion and timeliness of BERT utilization.
      Methods: We conducted a retrospective cohort study of pediatric patients
      undergoing anesthesia at Lucile Packard Children's Hospital Stanford between
      February 1, 2016, and October 1, 2016. Logistic regression compared induction
      cooperation between groups. Multinomial logistic regression compared patients'
      emotion at induction. Ordinary least squares regression compared preoperative
      time. Results: Of the 686 eligible patients, 163 were in the BERT group and 150
      in the midazolam. Ninety-three percentage of study patients (290/313) were
      cooperative at induction, and the BERT group were less likely to be cooperative
      (P = 0.04). The BERT group was more likely to be "playful" compared with
      "sedated" (P < 0.001). There was a reduction of 14.7 minutes in preoperative
      patient readiness associated with BERT (P = 0.001). Conclusions: Although most
      patients were cooperative for induction in both groups, the midazolam group was
      more cooperative. The BERT reduced the preinduction time and was associated with
      an increase in patients feeling "playful."

PMID- 30229199
TI  - I-PASS Handoff Program: Use of a Campaign to Effect Transformational Change.
AB  - Background: Behavior change is notoriously difficult to achieve within health
      care systems. Successful implementation of the I-PASS handoff bundle with
      subsequent decreases in medical errors and preventable adverse events represents
      an example of successful transformational change within academic medical centers.
      Objective: We designed a campaign to support and enhance uptake of the I-PASS
      handoff bundle at 9 study sites from 2011 to 2013. Methods: Following Kotter's
      model of transformational change, we established urgency using local data and
      institutional mandates, and site leaders built local guiding coalitions with
      institutional leaders, key faculty, and Chief Residents. We created and
      communicated our vision using a branded campaign and empowered others to act by
      soliciting and acting on feedback and supporting systems changes. Site leaders
      planned for and created short-term wins by recognizing residents who engaged with
      I-PASS, consolidated improvements, and institutionalized new approaches. Results:
      Implementation of I-PASS was successful, with achievement of substantial
      improvements in rates of medical errors and preventable adverse events. Data from
      the initial I-PASS study have continued to drive a national campaign that has
      included national recognition by leaders in the field of patient safety and
      pediatrics. Momentum has increased significantly to support mentored
      implementation of the I-PASS handoff program at over 35 academic medical centers
      across North America. Conclusions: I-PASS provides an example of transformational
      change achieved through a combination of educational interventions and change
      management to address resistance/barriers, supported by a robust campaign. We
      encourage others in academic medicine to consider using change models, including
      campaigns, to support health care improvement programs.

PMID- 30229200
TI  - Decreasing Radiograph Errors in Pediatric Sports Medicine Clinic.
AB  - Background: Radiographs are frequently ordered for general musculoskeletal
      complaints in the outpatient setting. However, incorrect laterality, incorrect
      location, or unnecessary radiographs have been reported as errors in our clinics.
      This quality improvement (QI) project aimed to reduce incorrect duplicate
      radiographs in outpatient pediatric sports medicine clinic. The overall global
      goal was to stop unnecessary radiation exposure in our pediatric patients.
      Methods: Using QI methodology, we evaluated the current clinic flow, the process
      of ordering radiographs, and the completion of radiographs at the main sports
      medicine outpatient clinic. Staff communication, staff education, and patient
      participation were identified as the prominent gaps in our clinic process. We
      implemented interventions using progressive biweekly Plan-Do-Study-Act (PDSA)
      cycles to promote change and to reduce our radiographic errors. Results:
      Retrospective baseline data demonstrated baseline errors of 9% (10/106) in the
      main outpatient clinic. After 6 months of PDSA cycles, we found no duplicate
      errors. Highly successful interventions included radiograph screening survey for
      families, staff education, and improved staff communication. The project was
      expanded to a second outpatient clinic with baseline errors of 6% (4/64). After 2
      months of PDSA cycles, no duplicate errors were found. Conclusion: Our goal was
      to reduce incorrect duplicate radiographs in outpatient sports medicine clinic
      and limit unnecessary radiation exposure in our pediatric patients. A reduction
      in duplicate errors at 2 clinics occurred using the Institute for Healthcare
      Improvement model to facilitate change. Effective communication between
      physicians, clinical athletic trainers, radiology technologists, patients, and
      families drove the success of this quality improvement initiative.

PMID- 30229201
TI  - A Quality Improvement Initiative to Decrease Time to Antibiotics for Children
      with Intestinal Failure, Fever, and a Central Line.
AB  - Introduction: Pediatric intestinal failure (IF) patients experience significant
      morbidity, including sepsis related to central line-associated bloodstream
      infections. Adult studies of sepsis demonstrate an association between time to
      antibiotic administration (TTA) and mortality. To overcome challenges in treating
      pediatric IF patients in an emergency department (ED), we appropriated an
      existing, reliable system for febrile immunocompromised oncology/bone marrow
      transplant children. We describe the translation of this process to febrile IF
      patients in the ED and steps toward sustained improvement. Methods: We formed a
      multidisciplinary team and used the Model for Improvement to define aims and
      identify key drivers. The goal was to use an existing improvement process to
      increase the percentage of patients with IF who receive antibiotics within 60
      minutes of arrival to the ED from 46% to 90%. Key drivers included pre- and
      postarrival processes, staff and family engagement, and a preoccupation with
      failure. We performed Plan-Do-Study-Act cycles targeting family engagement,
      prearrival efficiency, and postarrival consistency. Results: Two hundred seventy
      six encounters involving febrile IF patients between November 2012 and March 2017
      were evaluated. There was a sustained reduction in the median time from arrival
      to antibiotic administration (71-45 minutes). We decreased TTA to less than 60
      minutes for 77% of febrile IF patients. Conclusions: The basic tenets of process
      improvement for 1 high-risk population can be translated to another high-risk
      population but must be adjusted for variability in characteristics.

PMID- 30229202
TI  - Implementing a Standardized Clinical Pathway Leads to Reduced Asthma Admissions
      and Health Care Costs.
AB  - Introduction: Asthma exacerbations are 1 of the leading causes of hospital
      admissions in children in the United States. High volumes in the emergency
      department can lead to delayed treatment. Several studies have shown that
      implementation of a standardized clinical pathway can improve adherence to
      evidence-based standards. The purpose of our quality improvement project was to
      develop a standardized pathway of care for children with asthma exacerbations to
      improve time to treatment and reduce admissions. Methods: The team used process
      mapping to review the current process of care for patients with asthma
      exacerbations presenting to the Emergency Department. After identification of
      several barriers, the team used plan-do-study-act cycles to develop a
      standardized clinical pathway of care for children based on their respiratory
      clinical score. Further interventions occurred after data collection and
      analyzation through run charts. Results: Implementation of a standardized
      clinical pathway for children with asthma presenting to the Emergency Department
      resulted in treatment with steroids in less than 60 minutes. Overall admissions
      were decreased from an average of 24% to 17% throughout the intervention period.
      We estimated cost savings for the institution at over $230,000 for the 2 years
      after implementation of the pathway. Conclusions: Using a multidisciplinary team
      approach to develop a standardized clinical pathway for a common childhood
      illness like asthma can result in reduced time to treatment and admissions.

PMID- 30229203
TI  - Total Parenteral Nutrition Standardization and Electronic Ordering to Reduce
      Errors: a Quality Improvement Initiative.
AB  - Introduction: Total parenteral nutrition (TPN) provides vital intravenous
      nutrition for patients who cannot tolerate enteral nutrition but is susceptible
      to medical errors due to its formulation, ordering, and administrative
      complexities. At Johns Hopkins All Children's Hospital, 22% of TPN orders
      required clarification of errors and averaged 10 minutes per order for error
      correction by pharmacists. Quality improvement methodology improved patient
      safety by standardizing TPN formulations and incorporating TPN ordering processes
      into the electronic medical record. Methods: A multidisciplinary group of
      providers developed standardized TPN solutions for neonatal and pediatric
      patients. Inclusion, exclusion, and discontinuation criteria were defined. The
      primary outcome measure was reducing TPN ordering error rate, and secondary
      outcomes were improving TPN ordering and processing time along with reducing
      blood draws. Through multiple plan-do-study-act cycles, we standardized TPN
      solutions, incorporated them in the electronic medical record, monitored blood
      draws, and evaluated resource efficiency. Data were analyzed using chi-square
      tests of independence and t tests for 2 independent samples. Results: The TPN
      ordering error rate significantly decreased from baseline of 22% to 3.2% over the
      final quarter of the study period, chi2 (1, N = 2,467) = 89.13, P < 0.001. Order
      processing time fell from 10 to 5 minutes by project end. The average number of
      blood draws decreased significantly from 6.2 (SD = 3.12) blood draws to 4.3 (SD =
      2.13) in the last quarter of the study, t (506) = 5.97, P < 0.001. Conclusions:
      Standardizing TPN and transitioning to electronic ordering effectively and
      significantly reduced ordering errors and processing time. It also substantially
      improved resource efficiency by reducing the number of blood draws.

PMID- 30229204
TI  - Improving Follow-up Skeletal Survey Compliance in Suspected Nonaccidental Trauma
      Patients: What's the FUSS About?
AB  - Introduction: Nonaccidental trauma (NAT) victims account for a significant
      percentage of our pediatric trauma population. The skeletal survey (SS) and
      follow-up skeletal survey (FUSS) are essential in the evaluation of selected NAT
      patients. We identified that our clinically indicated FUSS completion rate was
      suboptimal. We hypothesized that implementing an intervention of postdischarge
      follow-up in our pediatric surgery clinic would improve FUSS completion rates.
      Methods: A follow-up clinic for NAT patients was established in July 2013. A
      retrospective review was performed of all suspected NAT cases younger than 2
      years old seen at Kentucky Children's Hospital between November 2012 and February
      2014. The study population was divided into pre (Group 1) and postintervention
      (Group 2). Bivariate analysis was performed. Results: Group 1 consisted of 50
      patients (58% male; median age, 9 months). Forty-7 (94%) had an SS; fractures
      were identified in 37 (74%) patients. Only 20 patients (40%) had FUSS; of those,
      4 had newly identified fractures. Group 2 consisted of 52 patients (54% male;
      median age, 7 months). All 52 children (100%) had an SS; fractures were
      identified in 35 (67%) patients. Forty-seven patients (90%) had FUSS. Of those, 6
      had new radiographic findings. Thirty-five patients (67%) were seen in our
      clinic. This improvement in FUSS (40% versus 90%) was statistically significant,
      P < 0.001. Conclusion: The decision to follow NAT patients in our clinic had
      significantly increased our rates of FUSS completion. This additional clinic
      follow-up also provided more evidence for NAT evaluation.

PMID- 30229206
TI  - Welcome to JBJS Open Access!: Authoritative and Accessible.

PMID- 30229205
TI  - Quality Initiative to Improve time to Antibiotics for Febrile Pediatric Patients
      with Potential Neutropenia.
AB  - Introduction: In patients who are immunocompromised, fever may indicate a life
      threatening infection. Prompt time to antibiotic administration in febrile
      patients at risk for neutropenia has been identified by national and
      international panels as a key benchmark of quality care in emergent situations. A
      quality improvement initiative to improve health care provided in a pediatric
      emergency department (ED) is described. Methods: A clinical pathway was
      previously initiated in a pediatric ED with a goal of improving time to
      antibiotics for febrile neutropenia patients. An agreed upon pathway and order
      set being initiated. Improvements were seen but not to the desired level. This
      project involved an improvement cycle that focused on nonvalue added time in the
      workflow. Results: Percent of patients receiving antibiotics within the goal time
      of 1 hour increased from 40% to 80% with the intervention. Process measures
      including arrival to ED bed time, ED bed to antibiotic order time and antibiotic
      order time to delivery time were followed. Conclusion: Clinical guidelines, order
      sets and detailed understanding of the actual workflow at the point of care
      delivery can be instrumental in achieving the goals of reducing time to
      antibiotics.

PMID- 30229207
TI  - Introducing JBJS Open Access.

PMID- 30229208
TI  - Interrater Reliability and Age-Based Normative Values for Radiographic Indices of
      the Ankle Syndesmosis in Children.
AB  - Background: While recent research has investigated the normative values,
      discriminative capacity, and interrater reliability of radiographic indices for
      the evaluation of the syndesmosis in adults, no such data exist for children. The
      purposes of the present study were (1) to determine the interrater reliability of
      common radiographic measures of syndesmosis and deltoid ligament competency in
      children and (2) to establish age-based normative values. Methods: A consecutive
      series of patient radiographs from a Level-I pediatric trauma center were
      identified and were used to create an age and sex-balanced cohort of 282
      patients. Subjects between 2 and 17 years of age were randomly selected from a
      pool of patients who had a complete 3-view (anteroposterior, lateral, and
      mortise) radiographic ankle series and a final diagnosis without osseous or
      ligamentous injury. Eight age and sex-balanced groups were created for analysis.
      Three independent raters evaluated all radiographs and recorded radiographic
      indices that are commonly used for the evaluation of ankle trauma: width of
      medial clear space, width of superior clear space, tibiofibular clear space,
      tibiofibular overlap, and medial clear space/superior clear space ratio.
      Interrater reliability was calculated with use of the intraclass correlation
      coefficient (ICC); means and standard deviations were used to report age-group
      normative values. Results: Two hundred and eighty-two patients (mean age [and
      standard deviation], 9.6 +/- 4.6 years) were analyzed. The superior clear space
      and tibiofibular overlap demonstrated excellent interrater reliability (ICC =
      0.915 and 0.964, respectively), the medial clear space and tibiofibular clear
      space demonstrated substantial agreement (ICC = 0.656 and 0.635, respectively),
      and the medial clear space/superior clear space ratio demonstrated moderate
      agreement (ICC = 0.418). The medial clear space could not be reliably measured
      until the age of 8 years because of insufficient ossification of the medial
      malleolus. Tibiofibular overlap demonstrated a linear increase over time, ranging
      from -1.4 mm in 2 and 3-year-old patients to 6.7 mm in 16 and 17-year-old
      patients (R2 = 0.995). Normative values varied by age and sex. Conclusions: The
      medial clear space and medial clear space/superior clear space ratio could not be
      reliably assessed for children under 8 years of age and were thus characterized
      by suboptimal interrater reliability. Tibiofibular overlap had excellent
      interrater agreement, changed predictably with skeletal growth, and may be useful
      for future research as well as the clinical assessment of pediatric ankle
      injuries to guide clinical decision-making. Level of Evidence: Diagnostic Level
      III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30229209
TI  - Postoperative Hyperglycemia Can Be Safely and Effectively Controlled in Both
      Diabetic and Nondiabetic Patients with Use of a Subcutaneous Insulin Protocol.
AB  - Background: Postoperative hyperglycemia related to stress has been shown to be an
      independent risk factor for periprosthetic joint infection. In a non-intensive
      care, general-surgery setting, a standardized postoperative insulin protocol has
      been shown to decrease the rate of wound infections. We hypothesized that the use
      of a similar protocol is both safe and effective for controlling hyperglycemia in
      patients who have undergone total joint replacement. Methods: We performed a
      retrospective cohort study of 489 consecutive patients who underwent primary or
      revision total hip or knee arthroplasty between January 2008 and April 2013. All
      patients were tested with point-of-care (finger-stick) glucose determinations
      postoperatively and were started on a subcutaneous insulin protocol if they had
      postoperative stress hyperglycemia of >140 mg/dL when fasting or >180 mg/dL after
      meals. Insulin was discontinued when blood glucose decreased to <100 mg/dL.
      Results: Of the 489 patients, 301 (62%) qualified for the insulin protocol.
      Thirty-seven (17%) of the 220 patients for whom the hemoglobin A1c level was
      available were diabetic, and 21 (11%) of the 187 patients for whom body mass
      index data were available were morbidly obese (body mass index, >=40 kg/m2).
      Diabetes (p < 0.001), revision surgery (p < 0.001), male sex (p = 0.0110), and
      obesity (including morbid obesity) (p = 0.0051) were independent factors
      resulting in significant glycemic elevation. A trend toward hyperglycemia
      occurred in younger patients but did not reach significance (p = 0.063). The
      glucose levels of patients in all of these groups responded well to insulin. None
      of the patients who were managed with the insulin experienced a periprosthetic
      joint infection. There were no injuries related to hypoglycemia. Conclusions: The
      findings of the present study suggest that hyperglycemia is a common link between
      seemingly disparate factors related to the increased prevalence of periprosthetic
      joint infection. The standardized subcutaneous insulin protocol was both safe and
      effective for the treatment of hyperglycemia for nondiabetic as well as diabetic
      patients. Patients who have undergone total joint replacement, especially those
      with revision procedures, male sex, morbid obesity, and diabetes, should be
      evaluated for hyperglycemia starting in the post-anesthesia care unit and should
      be managed with the insulin protocol when that risk is identified. Level of
      Evidence: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 30229210
TI  - Reliability and Validity of Radiographic Measurement of the Humerus-Elbow-Wrist
      Angle in Healthy Children.
AB  - : This article was updated on May 4, 2017, because of a previous error. The
      proximal line drawn in Figure 1 was different from the line described in the
      Materials and Methods section, which reads "The proximal line was drawn at the
      level of the radial tuberosity, and the distal line was made at the level of the
      top of the radial bowing (Fig. 1)." The correct figure is presented in this
      version of the article. An erratum has been published: JBJS Open Access. 2017 May
      26;2(2):e0012ER. Background: We conducted a retrospective cohort study to
      evaluate the normal value, range, reliability, and validity of measurement of the
      humerus-elbow-wrist angle, an index of valgus-varus angulation of the elbow, in
      healthy children. This measurement has been used to assess postoperative
      radiographic results. Methods: Radiographs of the elbow in 62 healthy children
      ranging from 2 to 11 years of age were reviewed by 6 examiners at 2 sessions. The
      mean value and the reliability of measurement of the humerus-elbow-wrist angle,
      the carrying angle, and the Baumann angle were assessed. Intraobserver and
      interobserver reliability were calculated with use of intraclass correlation
      coefficients (ICCs). To determine concurrent validity, the association between
      the humerus-elbow-wrist angle and carrying angle measurements was examined with
      use of Pearson correlation coefficients. Results: The mean humerus-elbow-wrist
      angle value was 12.0 degrees  (range, 1 degrees  to 24 degrees ), and the mean
      carrying angle was 14.6 degrees  (range, 4 degrees  to 28 degrees ). The ICCs for
      intraobserver measurements of the humerus-elbow-wrist angle were almost perfect
      for 4 examiners and were substantial for 2 examiners, with a mean value of 0.85
      (range, 0.73 to 0.94). The ICCs for interobserver reliability with regard to the
      first and second measurements of the humerus-elbow-wrist angle were both
      substantial (0.76 and 0.78). A significant association between the humerus-elbow
      wrist angle and the carrying angle was observed, with the Pearson correlation
      coefficients ranging from 0.74 to 0.90 (p < 0.001). Conclusions: Measurement of
      the humerus-elbow-wrist angle demonstrated good reliability and validity. The
      humerus-elbow-wrist angle is a reliable radiographic measure of coronal alignment
      of the humerus and forearm.

PMID- 30229211
TI  - Favorable Clinical and Radiographic Results of Transtrochanteric Anterior
      Rotational Osteotomy for Collapsed Subchondral Insufficiency Fracture of the
      Femoral Head in Young Adults.
AB  - Background: Subchondral insufficiency fracture of the femoral head (SIF) occurs
      infrequently in young adults. As the collapsed SIF lesion is usually located at
      the anterior portion of the femoral head, young adults with SIF are considered to
      be candidates for transtrochanteric anterior rotational osteotomy, similar to
      patients with osteonecrosis of the femoral head (ON). In the present study, we
      assessed the clinical and radiographic results of anterior rotational osteotomy
      for the treatment of SIF as compared with ON. Methods: We retrospectively
      reviewed 28 consecutive patients who underwent anterior rotational osteotomy for
      the treatment of unilateral SIF (7 patients) or unilateral ON (21 patients). The
      mean duration of follow-up was 3.7 years (range, 2.0 to 6.2 years). Clinical and
      radiographic assessments were performed with use of the Harris hip score (HHS),
      sequential radiographs, and single-photon emission computed tomography/computed
      tomography (SPECT/CT) with 99mTc-hydroxymethylene diphosphonate performed 5 weeks
      after surgery. Results: The mean HHS (and standard deviation) in the SIF group
      improved significantly from 51.6 +/- 11.7 preoperatively to 91.9 +/- 7.1 at 1
      year after surgery and to 96.9 +/- 3.8 at the time of the latest follow-up (p =
      0.0010 and 0.0002, respectively). Similarly, the mean HHS in the ON group
      improved significantly from 52.4 +/- 13.7 preoperatively to 80.7 +/- 10.0 at 1
      year after surgery and to 88.2 +/- 12.6 at the time of the latest follow-up (p <
      0.0001 for both). The HHS was significantly higher in the SIF group than in the
      ON group at 1 year after surgery (p = 0.019), but there was no significant
      difference between the groups at the time of the latest follow-up (p = 0.10). A
      postoperative intact ratio (calculated as the intact area of the femoral head
      divided by the weight-bearing area of the acetabulum on an anteroposterior
      radiograph) of >80% was achieved in association with smaller femoral neck-shaft
      varus angles in the SIF group (10.0 degrees  +/- 4.2 degrees ) as compared with
      the ON group (15.3 degrees  +/- 8.2 degrees ). Postoperative progression of
      collapse at the anteriorly rotated subchondral lesion was observed in 5 patients
      (23.8%) in the ON group but no patients in the SIF group. SPECT/CT images showed
      that rate of increased tracer uptake at the collapsed lesions in the SIF group
      was significantly higher than that in the ON group (p < 0.0001). Conclusions: The
      present study suggested that the absence of progression of collapse and a
      sufficient postoperative intact ratio without the need for marked varus
      realignment may be associated with favorable results following anterior
      rotational osteotomy for the treatment of SIF in young adults. Level of Evidence:
      Therapeutic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 30229212
TI  - Combined Intravenous and Intra-Articular Tranexamic Acid in Simultaneous
      Bilateral Total Knee Arthroplasty without Tourniquet Use.
AB  - Background: A combined intravenous and intra-articular regimen is one of the most
      effective administration routes of tranexamic acid (TXA) to reduce perioperative
      blood loss in unilateral total knee arthroplasty. However, there have been few
      reports regarding use of the combined regimen for patients undergoing
      simultaneous bilateral total knee arthroplasty, in which blood-management
      strategy is more challenging. Methods: We compared perioperative blood loss in 30
      consecutive patients undergoing simultaneous bilateral total knee arthroplasty
      who received both 1,000 mg of TXA intravenously and 1,000 mg of intra-articular
      TXA in each knee (combined TXA group) with that in a consecutive series of 51
      patients who only received 1,000 mg of TXA intravenously (intravenous TXA group).
      Additional intravenous TXA was administered 6 hours after the initial
      administration in both groups. Except for the intraoperative TXA administration
      regimen, an identical perioperative blood-management strategy was applied to both
      groups; this consisted of transfusion of 800 or 400 mL of predeposited autologous
      blood except for patients with a preoperative hemoglobin level of <11.0 g/dL, who
      received 4 units of allogenic blood. All surgical procedures were performed with
      spinal anesthesia and without use of a pneumatic tourniquet. Perioperative blood
      loss was calculated using the blood volume and change in hemoglobin level from
      the preoperative measurement to postoperative day 3. Results: There was
      significantly less perioperative blood loss in the combined TXA group compared
      with the intravenous TXA group (mean and standard deviation, 1,201 +/- 347 versus
      1,638 +/- 400 mL, respectively; mean difference, 437 mL; 95% confidence interval,
      263 to 613 mL; p < 0.0001). No patient in the combined TXA group and 1 patient
      (2%) in the intravenous TXA group required additional allogenic blood
      transfusion. No thrombotic events occurred in either group. Conclusions: In a
      nonrandomized comparison, combined intra-articular and intravenous TXA
      significantly reduced the calculated perioperative blood loss in simultaneous
      bilateral total knee arthroplasty compared with that found in patients treated
      only with intravenous TXA. Level of Evidence: Therapeutic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30229213
TI  - Clinical Results and Prognostic Factors for Outcomes of Valgus Femoral Osteotomy
      Combined with Chiari Pelvic Osteotomy for Osteoarthritis of the Hip.
AB  - Background: Surgeons have long debated whether advanced or end-stage
      osteoarthritis of the hip in young patients should be treated with total hip
      arthroplasty or osteotomy. We reviewed the intermediate-term clinical results of
      valgus femoral osteotomy combined with Chiari pelvic osteotomy (VCO) for advanced
      or end-stage osteoarthritis associated with severe acetabular dysplasia of the
      hip in young patients and analyzed prognostic factors related to conversion to
      total hip arthroplasty. Methods: The study group included 54 hips in 50 patients
      (5 men and 45 women; average age at the time of surgery, 45.6 years). The minimum
      and average durations of follow-up were 10 and 17.6 years, respectively. The
      Japanese Orthopaedic Association hip score (JOA score) was used for clinical
      evaluation. The probability of survival of the VCO from the time of the operation
      until the end point of conversion to total hip arthroplasty was calculated with
      use of the Kaplan-Meier method. We defined prognostic factors of outcome
      (conversion to total hip arthroplasty) with the Cox proportional hazards model.
      Results: The mean total JOA score increased from 53.0 points preoperatively to
      77.1 points at 1 year postoperatively, 81.6 points at 5 years, and 76.8 points at
      10 years. The survival rates were 83.3%, 59.7%, and 46.9% at 10, 15, and 20
      years, respectively. On univariate and multivariate analyses, patients with a low
      degree of acetabular roof obliquity had better postoperative results.
      Conclusions: VCO is a surgical approach that preserves joint function in young
      patients with advanced or end-stage osteoarthritis associated with severe
      acetabular dysplasia of the hip. The postoperative prognosis of VCO was improved
      in patients with a low degree of acetabular roof obliquity. Level of Evidence:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 30229214
TI  - Partial Resurfacing of the Knee with the BioPoly Implant: Interim Report at 2
      Years.
AB  - Background: Current treatments for focal chondral and osteochondral lesions of
      the femoral condyle have been associated with variable outcomes. We conducted a
      clinical trial of the BioPoly RS Partial Resurfacing Knee Implant to address this
      unmet need. Methods: We performed a single-arm, prospective study in which 33
      patients with focal cartilage lesions affecting the femoral condyle were managed
      with the BioPoly RS Partial Resurfacing Knee Implant. Knee injury and
      Osteoarthritis Outcome Score (KOOS) scores, a visual analog scale (VAS) for pain,
      the Short Form-36 (SF-36) physical component score , and the Tegner activity
      score were used to assess outcomes preoperatively and at 6 months, 1 year, and 2
      years postoperatively. The KOOS outcomes at 2 years were compared with historical
      outcomes following microfracture treatment. Results: We found significant and
      clinically meaningful improvements in the KOOS scores, VAS pain score, and SF-36
      physical component score (p < 0.025) when the values at all 3 postoperative time
      points were compared with the preoperative scores, and we also found significant
      improvements when the Tegner activity score at 2 years was compared with the
      preoperative score (p < 0.025). More than half of the cohort of patients had had
      a previous failure of cartilage-repair procedures. No significant differences
      were detected between younger patients (<=40 years) and older patients (>40
      years). When compared with historical microfracture data, the BioPoly RS Implant
      demonstrated significantly superior KOOS scores for quality of life and sports.
      Conclusions: The present study indicated that the BioPoly RS Partial Resurfacing
      Knee Implant is safe, that it resulted in significantly improved knee function by
      6 months, and that this improvement was sustained for 2 years regardless of
      patient age. The BioPoly RS Knee Implant allows return to a higher level of
      sporting activity than microfracture. Additional long-term follow-up is needed to
      determine the long-term effects of the device. Level of Evidence: Therapeutic
      Level IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30229215
TI  - Availability of Additional Mediolateral Implant Option During Total Knee
      Arthroplasty Improves Femoral Component Fit Across Ethnicities: Results of a
      Multicenter Study.
AB  - Background: Anatomical variation may represent a challenge in achieving a close
      fit between a prosthesis and a patient's osseous geometry in total knee
      arthroplasty (TKA). The purposes of this study were to determine whether the
      shape of the distal part of the femur differs among ethnicities, whether these
      differences affect the fit of the femoral component of a standard prosthesis, and
      whether the additional availability of a femoral component with a reduced
      mediolateral dimension for the same anteroposterior dimension improves femoral
      component fit across ethnicities. Methods: Femoral dimensions were measured
      intraoperatively during 967 TKAs performed using the same type of prosthesis in
      patients of 5 different ethnicities. Aspect ratios were calculated to determine
      whether the shapes of the femora differed among ethnicities. The component fit
      ("perfect," overhang, or underhang) when only standard prostheses were available
      was compared with the fit when both standard and narrow prostheses were available
      in all ethnic groups. This enabled us to determine whether the femoral component
      fit was improved by the additional availability of the narrow version. Results:
      Wide variations in shape were found among ethnicities as were variations among
      individuals of the same ethnicity. Differences in shape among ethnicities
      influenced the rate of overhang. However, overhang was more frequent at the
      trochlear than at the condylar level across all ethnicities. The availability of
      both the standard and the narrow femoral components improved the rate of a
      perfect fit in women in 3 of the 5 ethnic groups and reduced the overhang rate in
      women in all 5 of the ethnic groups. In contrast, only modest improvements in
      femoral component fit, which were not statistically significant, were seen in
      men. Conclusions: The shape of the distal part of the femur varies not only among
      ethnicities but also within ethnic groups, leading to a high prevalence of
      overhang when only standard prostheses are available. The additional availability
      of a femoral component with a reduced mediolateral dimension for the same
      anteroposterior size can reduce overhang and improve component fit across
      ethnicities.

PMID- 30229218
TI  - Erratum.
AB  - [This corrects the article on p. e00012 in vol. 2.].

PMID- 30229217
TI  - Percutaneous Palliative Surgery for Femoral Neck Metastasis Using Hollow
      Perforated Screw Fixation and Bone Cement.
AB  - Background: We introduced a new surgical method of percutaneous hollow perforated
      screw (HPS) fixation with concomitant bone-cement injection for the treatment of
      femoral neck metastasis and evaluated its efficacy for the palliative treatment
      of patients with advanced cancer. Methods: The study included 87 patients (39 men
      and 48 women; mean age [and standard deviation], 64.2 +/- 10.2 years; mean body
      mass index, 24.3 +/- 3.2 kg/m2) who underwent percutaneous HPS fixation and
      cementoplasty (mean cement amount, 19.8 +/- 8.3 mL) for the treatment of
      unilateral or bilateral femoral neck metastasis (total, 95 sites). Anesthesia
      type, operative time, operative blood loss, pain score changes (according to a
      visual analog scale [VAS]), walking status, and complications were assessed. The
      mean duration of follow-up was 10.1 +/- 10.8 months (range, 2 to 43 months).
      Results: The majority of procedures were performed with local (3 patients) or
      spinal (72 patients) anesthesia (total, 75 patients; 86.2%). The mean operative
      time was 35.9 minutes, and the mean operative blood loss was 97.0 mL. The VAS
      score for pain improved significantly, from 6.8 +/- 2.8 preoperatively to 2.8 +/-
      2.3 and 2.9 +/- 2.8 at 1 and 6 weeks postoperatively (p < 0.001). At 6 weeks
      postoperatively, 63 (80.8%) of 78 patients were able to walk (with either normal
      or limping gait, a cane or crutch, or a walker). The prevalence of major local
      complications (cement leakage into the hip joint, fixation failure) was 10.5% (10
      of 95), but major systemic complications (distant cement embolism) were not
      found. Conclusions: Percutaneous HPS fixation and cementoplasty for the treatment
      of femoral neck metastasis is a minimally invasive technique that provides
      effective pain relief and early stabilization. This technique seems to be useful
      for patients with advanced cancer for whom open surgery would be hazardous. Level
      of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 30229216
TI  - Intramedullary Nailing with a Suprapatellar Approach and Condylar Bolts for the
      Treatment of Bicondylar Fractures of the Tibial Plateau.
AB  - Background: Bicondylar tibial plateau fractures have been treated with either
      plating or external fixation techniques, with conflicting results. A recently
      introduced technique involving the combined use of intramedullary nailing via a
      suprapatellar approach and condylar bolts could represent a new pathway toward
      better treatment of this severe injury. Methods: The present report describes a
      retrospective and prospective study of all 17 patients (age range, 25 to 75
      years) who were admitted under the author's care for the treatment of a closed,
      bicondylar tibial plateau fracture between 2013 and 2015. All patients consented
      to undergo fixation of the fracture with intramedullary nailing through a
      suprapatellar approach and with use of condylar bolts. The reconstructed
      articular surface was supported with freeze-dried allograft that had been
      previously soaked in concentrated bone marrow. The patients were followed at
      regular intervals, and the results were assessed with the Knee injury and
      Osteoarthritis Outcome Score (KOOS). Results: All patients were followed for at
      least 1 year (average and standard deviation, 25.23 +/- 8.95 months; range, 12 to
      46 months). All fractures united clinically and radiographically between 10 and
      22 weeks (average, 15.1 +/- 2.91 weeks), with no instances of neurovascular
      complication, infection, or implant failure. One patient underwent early revision
      of the fixation because of unsatisfactory reduction of the articular surface, and
      1 patient had secondary fracture displacement. One condylar bolt was removed
      after fracture healing because of irritation at the insertion site. However, all
      patients regained knee motion without physiotherapy and all were fully weight
      bearing by the fifth postoperative month. Conclusions: The short and intermediate
      term results associated with the use of the proposed technique appear to be
      satisfactory. However, the effectiveness of the technique should be reassessed
      with long-term studies as well as comparative studies involving other fixation
      techniques. Level of Evidence: Therapeutic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 30229219
TI  - Anatomic Coracoclavicular Ligament Reconstruction for the Treatment of Acute
      Acromioclavicular Joint Dislocation: Minimum 10-Year Follow-up.
AB  - Background: The long-term clinical and radiographic outcomes following
      coracoclavicular (CC) ligament reconstruction for the operative treatment of
      acute acromioclavicular (AC) joint dislocation remain uncertain. The purpose of
      the present study was to determine the long-term clinical and radiographic
      outcomes of CC ligament reconstruction and to identify risk factors for
      unfavorable outcomes. Methods: We reviewed 20 cases of AC joint dislocation in 19
      patients (18 male and 1 female; mean age, 32.3 years) that were treated with
      single-bundle reconstruction. The mean duration of follow-up was 12.7 years. We
      measured the CC vertical distance (CCD) on the anteroposterior view and compared
      the affected and unaffected sides (CCD ratio). We divided the patients into those
      with a CCD ratio of <25% (Group 1) and those with a CCD ratio of >=25% (Group 2).
      We radiographically investigated the clavicular tunnel anteroposterior (CTAP)
      angle, clavicular tunnel ratio, and coracoid tunnel orientation on the basis of
      the entry and exit points at the base of the coracoid. For the coracoid tunnel
      orientation, we compared center-center orientation and noncenter-center
      orientation. Results: Group 1 comprised 17 cases (85%), and Group 2 comprised 3
      cases (15%). At the time of the latest follow-up, Group 1 had a significantly
      higher mean Constant score than Group 2 (98.2 compared with 90.7; p = 0.038). Of
      the 3 radiographic parameters, only the CTAP angle was significantly different
      between the 2 groups (p < 0.0001). Two (67%) of the 3 cases in Group 2 were
      associated with posterior AC joint displacement. Conclusions: CC ligament
      reconstruction for the treatment of acute AC joint dislocation resulted in
      successful long-term clinical and radiographic outcomes. It is important to
      decrease the CTAP angle and to ensure proper anatomic placement of the clavicular
      and coracoid tunnels at the time of surgery. Level of Evidence: Therapeutic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30229220
TI  - The Use of Ultrasound to Exclude Extremity Fractures in Adults.
AB  - Background: The purpose of the present study was to investigate whether
      ultrasonography can be used as a diagnostic tool to exclude extremity fractures
      in adults. Methods: This prospective comparative study involved 91 patients (age,
      >=18 years) who had been referred by general practitioners for a conventional
      radiographic examination of a suspected extremity fracture. No additional
      clinical examination was performed. Ultrasound examination was consistently
      carried out prior to conventional radiographic examination, which was regarded as
      the gold standard. At the end of the study, the positive scans were confirmed by
      a specialist who was highly skilled in ultrasonography. Results: The prevalence
      of fractures in the study population was 27%. Ultrasonography had a sensitivity
      of 92%, a specificity of 94%, a positive predictive value of 85%, a negative
      predictive value of 97%, a positive likelihood ratio of 15.33, and a negative
      likelihood ratio of 0.085. There seemed to be no association between the
      anomalous results and patient age or the specific anatomical region of the
      fracture. Conclusions: The present study indicates that ultrasonography, when
      performed and interpreted by experienced ultrasonographers, has high accuracy for
      the diagnosis of a suspected extremity fracture. No systematic differences were
      found between the results of radiography and ultrasonography, and ultrasonography
      showed a high sensitivity and specificity. Level of Evidence: Diagnostic Level
      II. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30229221
TI  - Coinfection with Hepatitis C and HIV Is a Risk Factor for Poor Outcomes After
      Total Knee Arthroplasty.
AB  - Background: As medical management continues to improve, orthopaedic surgeons are
      likely to encounter a greater proportion of patients who have coinfection with
      human immunodeficiency virus (HIV) and hepatitis-C virus (HCV). Methods: The New
      York Statewide Planning and Research Cooperative System (SPARCS) database was
      used to identify patients undergoing total knee arthroplasty between 2010 and
      2014. Patients were stratified into 4 groups on the basis of HCV and HIV status.
      Differences regarding baseline demographics, length of stay, total charges,
      discharge disposition, in-hospital complications and mortality, and 90-day
      hospital readmission were calculated. Results: Between 2010 and 2014, a total of
      137,801 patients underwent total knee arthroplasty. Of those, 99.13% (136,604) of
      the population were not infected, 0.62% (851) had HCV monoinfection, 0.20% (278)
      had HIV monoinfection, and 0.05% (68) were coinfected with both HCV and HIV.
      Coinfected patients were more likely to be younger, female, a member of a
      minority group, homeless, and insured by Medicare or Medicaid, and to have a
      history of substance abuse. HCV and HIV coinfection was a significant independent
      risk factor for increased length of hospital stay (odds ratio [OR], 2.9; 95%
      confidence interval [CI], 1.75 to 4.81), total hospital charges in the 90th
      percentile (OR, 2.02; 95% CI, 1.12 to 3.67), >=2 in-hospital complications (OR,
      2.04; 95% CI, 1.04 to 3.97), and 90-day hospital readmission (OR, 3.53; 95% CI,
      2.02 to 6.18). Conclusions: Patients coinfected with both HCV and HIV represent a
      rare but increasing population of individuals undergoing total knee arthroplasty.
      Recognition of unique baseline demographics in these patients that may lead to
      suboptimal outcomes will allow appropriate preoperative management and
      multidisciplinary coordination to reduce morbidity and mortality while containing
      costs. Level of Evidence: Prognostic Level III. See Instructions for Authors for
      a complete description of levels of evidence.

PMID- 30229222
TI  - Bone Graft Augmentation for Severe Glenoid Bone Loss in Primary Reverse Total
      Shoulder Arthroplasty: Outcomes and Evaluation of Host Bone Contact by 2D-3D
      Image Registration.
AB  - Background: The treatment of patients with severe glenoid bone loss using reverse
      total shoulder arthroplasty (RSA) is challenging because of the difficulty in
      obtaining glenoid fixation. The outcomes following primary RSA with structural
      bone-grafting for severe glenoid bone loss and the amount of native bone support
      necessary to achieve clinical improvement are unclear. Methods: We reviewed
      functional outcomes (American Shoulder and Elbow Surgeons [ASES] score, Simple
      Shoulder Test [SST], visual analog scale [VAS] for pain and function, patient
      satisfaction, and range of motion) for 57 patients who were treated with a
      primary RSA and glenoid bone-grafting for severe glenoid bone loss. Three
      glenoids were classified as type A2; 2, as type B2; and 2, as type C, according
      to the Walch classification; 16 glenoids, as grade E1; and 19, as grade E3,
      according to the Sirveaux classification; 9 glenoids, as grade 3, according to
      the Levigne classification; and 6 were unable to be classified. For the 44
      patients with adequate preoperative computed tomographic (CT) data and
      postoperative radiographs, we evaluated native bone contact under the glenoid
      baseplate by matching the projected shape of the implant and scapula from the
      postoperative radiographs with a generated 3-dimensional (3D) model of the
      preoperative scapula. We then analyzed functional outcomes in relation to native
      bone support of the baseplate. Results: At a mean of 46 months (minimum, 24
      months), the patients demonstrated significant improvements in function, motion,
      and pain (change in the ASES total score = 38.6, change in SST = 5.4, change in
      forward elevation = 72.4 degrees , change in abduction = 67.7 degrees , change in
      external rotation = 24.3 degrees , and change in VAS pain score = -4.6; p < 0.001
      for all). On the basis of the generated 3D model, the baseplate contact to host
      bone was a mean (and standard deviation) of 17% +/- 12% (range, 0% to 50%). There
      was no significant correlation between host bone coverage and change in the ASES
      score (p = 0.51) for the 44 patients included in this analysis. There were 4
      major complications (7%) in the study group but no glenoid baseplate failures.
      Conclusions: Glenoid bone-grafting in a primary RSA in a shoulder with severe
      bone loss produces good functional outcomes that do not correlate with the degree
      of native bone contact under the baseplate. We had observed no glenoid component
      failures at the time of writing. Level of Evidence: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30229223
TI  - Determinants of Health Status Three to Six Years After Surgical Treatment of
      Closed Ankle Fracture and Comparison with the General Population: A Historical
      Cohort Study.
AB  - Background: The purposes of the present study were to identify the determinants
      of health status 3 to 6 years after open reduction and internal fixation (ORIF)
      for the treatment of closed ankle fracture and to compare the health status of
      patients who had undergone this procedure with that in the general population
      after adjusting for sociodemographic variables, body mass index (BMI), and
      smoking status. Methods: The present study was a historical cohort study combined
      with a postal survey. In total, 1,149 patients who underwent ORIF for the
      treatment of closed ankle fractures at 2 hospitals were eligible for chart
      review; 959 with low-energy fractures were eligible for a postal survey, and 471
      (49%) responded to the Short Form Health Survey-36 (SF-36) health status
      questionnaire and provided data on BMI. Determinants of the physical functioning
      (PF), physical component summary (PCS), and mental component summary (MCS) scores
      of the SF-36 were analyzed by means of multivariable linear regression analysis.
      The health status of patients with an ankle fracture (n = 471) was compared with
      that in a sample of the general population (n = 5,396) by means of multivariable
      regression. Results: Age, American Society of Anesthesiologists (ASA) class III,
      and complications following surgery were associated with PF and PCS scores, and a
      BMI of >=30 kg/m2 and current smoking status was associated with PF and MCS
      scores. However, the PF, PCS, and MCS scores of patients with ankle fractures did
      not differ from those of the general population, with unstandardized regression
      coefficients of 0.25 (95% confidence interval [CI], -1.67 to 2.16; p = 0.80),
      0.67 (95% CI, -0.35 to 1.70; p = 0.199), and -0.57 (95% CI, -1.63 to 0.49; p =
      0.29), respectively. Conclusions: Age, ASA class III, and complications following
      surgery were associated with PF and PCS scores at 3 to 6 years after surgery for
      the treatment of closed ankle fractures. However, the health status of patients
      with ankle fractures did not differ from that in the general population after
      adjusting for differences in demographic variables, BMI, and smoking status.
      Level of Evidence: Therapeutic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 30229224
TI  - A Patient-Focused Technology-Enabled Program Improves Outcomes in Primary Total
      Hip and Knee Replacement Surgery.
AB  - Background: A patient-engagement and pathway-management program for patients
      undergoing primary total hip and knee replacement was evaluated. Health-service
      and multimedia features supported by technology were integrated with existing
      enhanced recovery after surgery (ERAS) practices. The primary objective was to
      demonstrate the impact on length of stay. The secondary objective was to assess
      the impact on clinical, patient-focused, and financial outcomes. Methods: Two
      thousand and eighty consecutive patients undergoing primary total hip replacement
      (n = 1,034) and total knee replacement (n = 1,046) were classified into "pre
      program" (retrospectively assessed [n = 1,038]) and "program" (prospectively
      assessed [n = 1,042]) cohorts. Patients in the program cohort were subdivided
      according to those who were eligible for criteria-based outreach support (OS) (n
      = 401) and those who were ineligible for this service (NOS) (n = 641). Clinical
      outcomes were assessed for all patients, and patient-focused outcomes were
      assessed for a subset (n = 223). Results: The mean reduction in length of stay
      ranged from 20% (1.2 days) to 42% (2.5 days) following total hip replacement and
      from 9% (0.6 day) to 31% (2 days) following total knee replacement (p < 0.001).
      Clinical outcomes (readmissions, complications, emergency department re
      attendance rates) were not significantly negatively impacted. The Oxford Hip
      Score had numerically larger improvement after total hip replacement in the OS
      group than in the pre-program group (4.1-point increase), and the Oxford Knee
      Score had numerically larger improvement after total knee replacement in the NOS
      group than in the pre-program group (0.8-point increase). The patients in the
      program cohort (either OS or NOS) rated overall health gain as higher than those
      in the pre-program cohort (gain in numerical rating scale, 1.4 points for
      patients managed with total hip replacement, 0.6 points for patients managed with
      total knee replacement). Older patients and those with higher comorbidity indices
      benefited most with respect to length of stay and multiple clinical outcomes.
      Patient experience was significantly improved across domains (p < 0.001 to p =
      0.003). Potential savings for patients managed with total hip replacement
      (L401.64 [$267.76] per patient) exceeded estimated program charges of L50
      [$33.33] to L60 [$40] per patient, whereas the potential savings for patients
      managed with total knee replacement (L76.67 [$51.11] per patient) were sufficient
      to achieve a reduction of total system costs. Conclusions: Technology-enabled
      programs may deliver enhanced care at lower costs for patients undergoing lower
      limb arthroplasty. Shorter durations of inpatient stay without a negative impact
      on clinical outcomes and improved patient-focused outcomes and experience can
      deliver substantial value that can be especially beneficial for older patients
      and those with greater medical complexity. Level of Evidence: Therapeutic Level
      III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30229225
TI  - Implant-Related Complications and Mortality After Use of Short or Long Gamma Nail
      for Intertrochanteric and Subtrochanteric Fractures: A Prospective Study with
      Minimum 13-Year Follow-up.
AB  - Background: The purpose of this study was to evaluate the rates of implant
      related complications and mortality after treatment of an intertrochanteric or
      subtrochanteric fracture with a short or long Gamma nail. Methods: Between
      September 1998 and August 2003, 644 patients at 2 centers treated with a long or
      short Gamma nail for a hip fracture were prospectively enrolled in this study.
      These patients were followed until they reached 1 of the study end points, which
      included death, a reoperation directly related to the Gamma nail, or the end date
      of the study. Results: The average age (and standard deviation) of the patients
      included in the study was 81.3 +/- 8.6 years at the time of the operation, and
      28.3% of the patients were male. The rate of implant-related complications was
      9.9%. The most common complications included peri-implant fracture (4.2%),
      proximal lateral thigh discomfort requiring extraction of the implant (2.0%), and
      lag-screw cutout (1.1%). Interestingly, more than half (56%) of the 27 peri
      implant fractures occurred >1.5 years after the index operation. The median time
      from the operation to death was 2.9 years (range, 0 to 17.1 years). The 30-day
      mortality rate after treatment was 9.5%. Patients with American Society of
      Anesthesiologists (ASA) class-3 or 4 physical status had a significantly higher
      risk of mortality than ASA class-1 patients. Conclusions: Gamma nails are
      effective in the treatment of intertrochanteric and subtrochanteric fractures.
      However, 9.8% of patients had complications requiring additional surgery. The
      most common serious complications include peri-implant fracture and lag-screw
      cutout. Several peri-implant fractures occurred long after the index procedure.
      Patients had a high rate of mortality (27%) after 1 year, and higher preoperative
      ASA class was found to be a predictor of increased risk of mortality. Therefore,
      clinicians must carefully consider patients' preoperative comorbidities when
      counselling patients on the risks of surgery. Level of Evidence: Therapeutic
      Level II. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30229226
TI  - Tip-Apex Distance Is Most Important of Six Predictors of Screw Cutout After
      Internal Fixation of Intertrochanteric Fractures in Women.
AB  - Background: Six risk factors for screw cutout after internal fixation of
      intertrochanteric fractures have been reported. The purpose of the present study
      was to evaluate and compare the impact of the 6 risk factors of screw cutout to
      clarify the most important one. Methods: We enrolled 8 consecutive patients who
      had screw cutout and 48 random control subjects after internal fixation of
      intertrochanteric fractures treated with proximal femoral nail antirotation
      systems at our institution. All of the patients were female. The group that had
      screw cutout and the control group were retrospectively evaluated and compared
      with respect to the OTA/AO classification, presence of a posterolateral fragment,
      types of reduction pattern on anteroposterior and lateral radiographic images,
      position of the screw, and the presence of a tip-apex distance (TAD) of >=20 mm.
      The impact of each factor on screw cutout was assessed using backward stepwise
      multivariable logistic regression analysis with the Akaike information criterion.
      Risk stratification was assessed using classification and regression tree (CART)
      analysis. Results: Among 6 risk factors, only a TAD of >=20 mm had a significant
      impact on screw cutout, with an adjusted odds ratio of 12.4 (95% confidence
      interval, 1.6 to 129.0; p = 0.019). CART analysis also demonstrated that a TAD of
      >=20 mm was the most important risk stratification factor (p < 0.001).
      Conclusions: Among the 6 previously reported screw cutout-related factors, only a
      TAD of >=20 mm was associated with screw cutout after internal fixation of
      intertrochanteric fractures with proximal femoral nail antirotation systems.
      Level of Evidence: Therapeutic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 30229228
TI  - Standardized Note Templates Improve Electronic Medical Record Documentation of
      Neurovascular Examinations for Pediatric Supracondylar Humeral Fractures.
AB  - Background: Optimization of the electronic medical record (EMR) is essential to
      support the clinician and to improve the quality and efficiency of patient care.
      The present report describes the development and implementation of a standardized
      template that is embedded in the EMR and is focused on a comprehensive physical
      examination during the evaluation of pediatric supracondylar humeral fractures.
      We compared the completeness of physical examinations as well as the timing of
      detection and documentation of neurovascular injuries before and after
      implementation of the template. We hypothesized that the use of a template would
      increase the completeness of examinations and would lead to earlier documentation
      of neurovascular injuries. Methods: A multidisciplinary quality-improvement task
      force was created to address neurovascular documentation practices for patients
      who underwent operative treatment of supracondylar humeral fractures. Following a
      series of formative and process evaluations, a standardized EMR template was
      implemented. Neurovascular examination documentation practices that were in use
      before (pre-template group, n = 224) and after (template group, n = 300) the
      implementation of the template were compared. Logistic regression analyses of the
      2 groups were used to compare the likelihood of a complete neurovascular
      examination and the timing of neurovascular injury identification. Results: There
      was significant improvement in the documentation of the vascular (odds ratio
      [OR], 70.7; 95% confidence interval [CI], 39.5 to 126.6; p < 0.0001), motor (OR,
      17.6; 95% CI, 9.5 to 32.7; p < 0.0001), and sensory (OR, 23.9; 95% CI, 12.9 to
      44.4; p < 0.0001) examinations in the template group. Neurological injuries were
      more likely to be identified preoperatively in the template group compared with
      the pre-template group (OR, 6.8; 95% CI, 1.7 to 27.1; p = 0.0067). Conclusions:
      The incorporation of a standardized template in the EMR improved the completeness
      and timing of documentation of neurological injury. Standardized EMR templates
      developed by a clinically driven multidisciplinary task force have the potential
      to improve the quality of clinical documentation and to ease communication among
      providers. Level of Evidence: Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 30229227
TI  - The Utility of False-Profile Radiographs for the Detection of Osteoarthritis
      Progression in Acetabular Dysplasia.
AB  - Background: Both the lateral center-edge angle and acetabular roof obliquity on
      anteroposterior radiographs are well-known prognostic predictors of
      osteoarthritis progression in patients with acetabular dysplasia. However, few
      studies have evaluated osteoarthritis progression on false-profile radiographs.
      In the present study, osteoarthritis progression was evaluated on anteroposterior
      and false-profile radiographs. Methods: We retrospectively evaluated 76 patients
      with acetabular dysplasia with Tonnis grade-0 or 1 osteoarthritis, from a group
      of 179 patients (209 hips), who had undergone unilateral periacetabular osteotomy
      from 1995 to 2005. We evaluated the hip joint of the contralateral, untreated
      side. All patients were followed for >=10 years. Of the 76 patients, 52 patients
      with Tonnis grade-0 or 1 osteoarthritis at the latest follow-up were categorized
      into the non-progression group and the remaining 24 patients with Tonnis grade-2
      or 3 osteoarthritis were categorized into the progression group. We evaluated
      patient characteristics as well as radiographic parameters, including the
      preoperative lateral center-edge angle, acetabular roof obliquity, and anterior
      center-edge angle. Results: The mean duration of follow-up was 12.6 years (range,
      10 to 19 years). On univariate analysis, body weight, body mass index, and all
      radiographic parameters indicating the severity of acetabular dysplasia
      significantly differed between the 2 groups. On multivariate analysis, both the
      anterior center-edge angle and acetabular roof obliquity were considered to be
      significant predictive factors for osteoarthritis progression. On receiver
      operating characteristic curve analysis, the cutoff values for the lateral center
      edge angle, acetabular roof obliquity, and anterior center-edge angle were 15.5
      degrees , 15.5 degrees , and 12.5 degrees , respectively. Conclusions: In
      addition to the lateral center-edge angle and acetabular roof obliquity, we
      showed that the anterior center-edge angle is a possible prognostic predictor of
      osteoarthritis progression. These findings indicate that radiographic parameters
      based on the false-profile view are relevant. Additionally, patients with an
      anterior center-edge angle of <=12.5 degrees  and a lateral center-edge angle of
      <=15.5 degrees  seem to be at higher risk of osteoarthritis progression over a 10
      year period. Level of Evidence: Prognostic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 30229229
TI  - Total Ankle Arthroplasty for Rheumatoid Arthritis in Japanese Patients: A
      Retrospective Study of Intermediate to Long-Term Follow-up.
AB  - Background: Outcomes after total ankle arthroplasty (TAA) combined with additive
      techniques (augmentation of bone strength, control of soft-tissue balance,
      adjustment of the loading axis) for the treatment of rheumatoid arthritis were
      evaluated after intermediate to long-term follow-up. The influences of biologic
      treatment on the outcomes after TAA were also evaluated. Methods: We performed a
      retrospective observational study involving 50 ankles (44 patients) that
      underwent TAA for the treatment of rheumatoid arthritis. The mean duration of
      follow-up was 7.1 years. Clinical outcomes were evaluated with use of the
      Japanese Society for Surgery of the Foot (JSSF) scale score and a postoperative
      self-administered foot-evaluation questionnaire (SAFE-Q). Radiographic findings
      were evaluated as well. These parameters also were compared between patients
      managed with and without biologic treatment. Results: This procedure
      significantly improved the clinical scores of the JSSF rheumatoid arthritis foot
      and ankle scale (p < 0.0001). Forty-eight of the 50 ankles had no revision TAA
      surgery. Subsidence of the talar component was seen in 8 ankles (6 in the
      biologic treatment group and 2 in the non-biologic treatment group); 2 of these
      ankles (both in the biologic treatment group) underwent revision TAA. The social
      functioning score of the SAFE-Q scale at the time of the latest follow-up was
      significantly higher in the biologic treatment group (p = 0.0079). The dosage of
      prednisolone (p = 0.0003), rate of usage of prednisolone (p = 0.0001), and
      disease-activity score (p < 0.01) at the time of the latest follow-up were all
      significantly lower in the biologic treatment group. Conclusions: TAA is
      recommended for the treatment of rheumatoid arthritis if disease control,
      augmentation of bone strength, control of soft-tissue balance, and adjustment of
      the loading axis are taken into account. The prevention of talar component
      subsidence remains a challenge in patients with the combination of subtalar
      fusion, rheumatoid arthritis, and higher social activity levels. Level of
      Evidence: Therapeutic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 30229230
TI  - The Anatomy of the Articularis Genus Muscle and Its Relation to the Extensor
      Apparatus of the Knee.
AB  - Background: The anatomy of the articularis genus muscle has prompted speculation
      that it elevates the suprapatellar bursa during extension of the knee joint.
      However, its architectural parameters indicate that this muscle is not capable of
      generating enough force to fulfill this function. The purpose of the present
      study was to investigate the anatomy of the articularis genus, with special
      emphasis on its relationship with the adjacent vastus intermedius and vastus
      medialis muscles. Methods: The articularis genus muscle was investigated in 18
      human cadaveric lower limbs with use of macrodissection techniques. All
      components of the quadriceps muscle group were traced from origin to insertion,
      and their affiliations were determined. Six limbs were cut transversely in the
      middle third of the thigh. The modes of origin and insertion of the articularis
      genus, its nerve supply, and its connections with the vastus intermedius and
      vastus medialis were studied. Results: The muscle bundles of the articularis
      genus were organized into 3 main layers: superficial, intermediate, and deep. The
      bundles of the superficial layer and, in 60% of the specimens, the bundles of the
      intermediate layer originated from both the vastus intermedius and the anterior
      and anterolateral surfaces of the femur. The bundles of the deep layer and, in
      40% of the specimens, the bundles of the intermediate layer arose solely from the
      anterior surface of the femur. The distal insertion sites included different
      levels of the suprapatellar bursa and the joint capsule. A number of connections
      between the articularis genus and the vastus intermedius were found. While the
      vastus medialis inserted into the whole length of the vastus intermedius
      aponeurosis, it included muscle fibers of the articularis genus, building an
      intricate muscle system supplied by nerve branches of the same medial deep
      division of the femoral nerve. Conclusions: The articularis genus, vastus
      medialis, and vastus intermedius have a complex, interacting architecture,
      suggesting that the articularis genus most likely does not act as an independent
      muscle. With support of the vastus intermedius and vastus medialis, the
      articularis genus might be able to function as a retractor of the suprapatellar
      bursa. The finding of likely interplay between the articularis genus, vastus
      intermedius, and vastus medialis is supported by their concurrent innervation.
      Clinical Relevance: The association between the articularis genus, vastus
      medialis, and vastus intermedius may be more complex than previously believed,
      and this close anatomical connection could have functional implications for knee
      surgery. Dysfunction, scarring, or postoperative arthrofibrosis of the
      sophisticated interactive mechanism needs further investigation.

PMID- 30229231
TI  - Magnetically Controlled Devices Parallel to the Spine in Children with Spinal
      Muscular Atrophy.
AB  - Background: Children with severe spinal deformity frequently are managed with
      growth-friendly implants. After initial surgery, externally controlled magnetic
      rods allow spinal deformity correction during growth without further surgical
      intervention. The ability to lengthen the spine without additional surgical
      procedures is especially beneficial in high-risk children, such as those with
      spinal muscular atrophy (SMA). The purpose of the present study was to assess the
      level of control of spinal deformity in a homogeneous group of patients with SMA
      who were managed with magnetically controlled implants for 2 years. Methods: This
      prospective, nonrandomized study included 21 non-ambulatory children with type-II
      SMA and progressive scoliosis who were managed bilaterally with a magnetically
      controlled implant that was inserted parallel to the spine with use of rib-to
      pelvis hook fixation. Radiographic measurements of scoliotic curves, kyphosis,
      lordosis, pelvic obliquity, and spinal length were performed before and after
      implantation of the magnetically controlled device and during external
      lengthening. The mean duration of follow-up was 2 years. Results: The mean main
      curve of patients without prior vertical expandable prosthetic titanium rib
      (VEPTR) treatment decreased from 70 degrees  before implantation of the
      magnetically controlled device to 30 degrees  after implantation of the device.
      Correction was maintained during the follow-up period, with a mean curve of 31
      degrees  at the time of the latest follow-up at 2.2 years. Pelvic obliquity was
      surgically corrected by 76% (from 17 degrees  to 4 degrees ) and remained stable
      during follow-up. Thoracic kyphosis could not be corrected within the follow-up
      period. Spinal length of children without prior spinal surgery increased by >50
      mm immediately after device implantation and steadily increased at a rate of 13.5
      mm/yr over the course of treatment. During treatment, 4 general complications
      occurred and 6 lengthening procedures failed, with 3 patients requiring surgical
      revision. Conclusions: Bilateral implantation of an externally controlled
      magnetic rod with rib-to-pelvis fixation represents a safe and efficient method
      to control spinal deformity in children with SMA, achieving sufficient and stable
      curve correction as well as increased spinal length. The complication rate was
      lower than those that have been described for VEPTR and other growing rod
      instrumentation strategies. Level of Evidence: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30229232
TI  - Pulsation and Collimation During Fluoroscopy to Decrease Radiation: A Cadaver
      Study.
AB  - Background: Awareness of the harmful effects of long-term low-dose radiation is
      rising. Many studies have assessed both patient and physician exposure to
      radiation in association with the use of fluoroscopy in the operating room.
      However, to our knowledge, previous studies have not assessed, in a detailed
      fashion, the reduction in radiation exposure that pulsation and collimation
      provide. Methods: Seven fresh cadavers were irradiated for 5 minutes with C-arm
      fluoroscopy with use of standard x-ray and pulsed and collimated x-ray beams. The
      x-ray sources were placed under the table, over the table, and lateral to the
      table. Radiation exposure doses were measured at different points, such as the
      center of the radiation field on the cadaver as well as at the locations of the
      surgeon's hand and thyroid gland. In addition, Monte Carlo simulation (a physics
      equation to predict exposure) was performed to estimate the dose reduction and to
      confirm the experimental results. Results: The radiation exposure doses
      associated with the use of pulsed fluoroscopy (8 times per second) were reduced
      by approximately 30% for the patient and by approximately 70% for the surgeon's
      hand and thyroid gland as compared with those associated with the use of
      continuous fluoroscopy. The radiation exposure doses associated with the use of
      collimated beams were reduced to approximately 65% for the surgeon's hand and
      thyroid gland as compared with those associated with the use of non-collimated
      fluoroscopy. These results were consistent with the simulation, and the phenomena
      could be appropriately explained by physics. Conclusions: The present study
      revealed the effectiveness of pulsed and collimated x-ray beams in reducing
      radiation exposure doses resulting from C-arm fluoroscopy. Surgeons should
      consider using the techniques of pulsed fluoroscopy and collimation to protect
      patients and themselves from radiation. Clinical Relevance: This study presents
      data regarding the reduction of radiation exposure provided by pulsed fluoroscopy
      and collimation.

PMID- 30229233
TI  - Total Knee Arthroplasty in a Low-Income Country: Short-Term Outcomes from a
      National Joint Registry.
AB  - Background: We describe our 10-year experience with total knee arthroplasty in
      patients who are included in the Malawi National Joint Registry. Methods: A total
      of 127 patients underwent 153 total knee arthroplasties (TKAs) between 2005 and
      2015. The mean duration of follow-up was 4 years and 3 months (range, 6 months to
      10 years and 6 months). The study group included 98 women and 29 men with a mean
      age of 65.3 years (range, 24 to 84 years). Nine patients were human
      immunodeficiency virus (HIV)-positive. Results: The primary indication for
      surgery was osteoarthritis (150 knees), and the mean preoperative and
      postoperative Oxford Knee Scores were 16.81 (range, 4 to 36) and 45.61 (range, 29
      to 48), respectively. Four knees (2.6%) were revised because of early
      periprosthetic joint infection (1 knee), aseptic loosening (1 knee), and late
      periprosthetic joint infection (2 knees). There were no perioperative deaths. In
      the group of 9 patients who were HIV-positive, there were no early or late
      complications and the mean Oxford Knee Score was 47 (range, 42 to 48) at the time
      of the latest follow-up. Conclusions: This study demonstrated good short-term
      results following 153 primary TKAs performed in a low-income country. Level of
      Evidence: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 30229234
TI  - A New, Easy, Fast, and Reliable Method to Correctly Classify Acetabular Fractures
      According to the Letournel System.
AB  - Background: Accurate classification of acetabular fractures remains difficult. To
      aid in the classification of acetabular fractures and to aid in teaching, our
      department developed a diagnostic algorithm that involves the use of 1
      standardized 3-dimensional reconstruction of a computed tomography (CT) scan (an
      exopelvic view without the femoral head) with 8 anatomical landmarks. The
      algorithm was integrated into a smartphone application (app). The main objective
      of this study was to test the efficacy of this algorithm and smartphone app.
      Methods: Fourteen reviewers (3 experts, 3 fellows, 3 residents, and 5 novice
      reviewers) evaluated a set of 35 CT scans of acetabular fractures in 2 phases.
      During the first phase, the scans (including axial 2-dimensional views and 3
      dimensional (3D) multiplanar reconstruction views) were assessed by each reviewer
      twice, with an interval of 4 weeks between the readings to decrease recall bias.
      During that phase, the reviewers were provided with a diagram of the Letournel
      classification system with no guidelines for interpretation. During the second
      phase, performed 4 weeks after the first phase, 1 standardized 3D reconstruction
      (an exopelvic view without the femoral head) was reviewed twice, with an interval
      of 4 weeks between the readings. During that phase, the reviewers used the
      smartphone app. The primary outcome was the accuracy of classification.
      Interobserver reliability, reading time, and time needed for accurate
      classification were noted. Results: The accuracy of fracture classification was
      64.5% when the standard method of analysis was used and 83.4% when the app was
      used (p < 0.001). Improvement was noted in all groups, with the expert group
      showing the least improvement (88.6% to 97.2%, p = 0.04) and the novice group
      showing the most improvement (42.0% to 75.5%, p < 0.001). Furthermore, use of the
      app greatly increased the accuracy of classification of complex fractures. The
      average reading time was 71.8 minutes when the standard method was used and 37.4
      minutes when the app was used. The interobserver reliability improved in all
      groups to an excellent reliability (interclass correlation coefficient [ICC] >
      0.79). Conclusions: The Letournel classification system is difficult to
      understand and to learn but remains the only system guiding the surgical strategy
      for acetabular fractures. The impact of diagnostic algorithms is debatable. The
      most important finding of the present study is the high accuracy for
      inexperienced groups when the app was used. Another important finding is the high
      reliability of this method for the diagnosis of complex acetabular fractures.

PMID- 30229236
TI  - Prevalence of and Predictive Factors for Scoliosis After Surgery for Congenital
      Heart Disease in the First Year of Life.
AB  - Background: The surgical treatment of congenital heart disease is reported to be
      associated with a high prevalence of scoliosis, although the detailed etiology is
      unknown. Surgical interventions involving the rib cage are considered to increase
      the risk of scoliosis. However, whether the cardiac condition or the procedure
      performed makes patients more susceptible to the development of spinal deformity
      is controversial. Methods: The present study included 483 patients who underwent
      surgery for the treatment of congenital heart disease with use of procedures
      involving the immature rib cage (sternotomy and/or thoracotomy) during the first
      year of life, followed by the evaluation of standing chest radiographs at >=10
      years of age. Patients with congenital spinal deformity and potential
      neuromuscular disease were excluded. The prevalence of and predictive factors for
      scoliosis were evaluated. The presence of scoliosis (Cobb angle >=10 degrees  to
      <20 degrees , >=20 degrees  to <30 degrees , >=30 degrees  to <45 degrees , >=45
      degrees ), the convex side of the curve, and the location of the curve were
      evaluated radiographically. Potential predictive factors that were analyzed
      included the age at the time of surgery, surgical approach, use of
      cardiopulmonary bypass, postoperative heart failure and/or cyanosis, New York
      Heart Association (NYHA) class, cardiomegaly, and age at the time of radiography.
      Results: The mean age at the time of surgery was 112 days, and the mean age at
      the time of radiography was 14.4 years. The prevalence of scoliosis was 42.4%,
      and the prevalences of >=10 degrees  to <20 degrees , >=20 degrees  to <30
      degrees , >=30 degrees  to <45 degrees , and >=45 degrees  scoliosis were 31.7%,
      5.8%, 2.5%, and 2.5%, respectively. Three patients underwent surgery for the
      treatment of progressive scoliosis. Multivariate analysis indicated that the
      predictive factors were female sex, left thoracotomy, bilateral thoracotomy, NYHA
      class, and age at the time of radiography for >=10 degrees  scoliosis;
      cardiomegaly, NYHA class, and age at the time of radiography for >=20 degrees 
      scoliosis; cardiomegaly, number of surgical procedures, and age at the time of
      radiography for >=30 degrees  scoliosis; and cardiomegaly for >=45 degrees 
      scoliosis. Age at the time of radiography was a predictor of <45 degrees 
      scoliosis; however, the relative association was small. Conclusions: Surgery for
      the treatment of congenital heart disease during the first year of life was
      associated with a high prevalence of scoliosis (>=40%). While female sex was one
      of several predictors of >=10 degrees  scoliosis, cardiomegaly was the sole
      predictor of >=45 degrees  scoliosis. Level of Evidence: Prognostic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30229235
TI  - The Effect of Rotator Cuff Repair on Natural History: A Systematic Review of
      Intermediate to Long-Term Outcomes.
AB  - Background: Rotator cuff disease can have a progressive natural history of
      increasing tear size and worsening function. It remains unknown whether rotator
      cuff repair alters this natural history. Methods: A systematic review of the
      intermediate to long-term (minimum 5-year) results of operative rotator cuff
      repair and no repair of rotator cuff injuries was performed to compare (1)
      patient-based outcomes, (2) future surgical intervention, (3) future tear
      progression or recurrence, and (4) tear size. The no-repair group included both
      conservative treatment and surgical treatment without repair. After the
      application of selection criteria, 29 studies with 1,583 patients remained. Meta
      regression was conducted to adjust for baseline age, sex, tear size, and duration
      of follow-up. Results: Comparison of the repair and no-repair groups revealed no
      significant differences in terms of age (p = 0.36), sex (p = 0.88), study level
      of evidence (p = 0.86), or Coleman methodology score (p = 0.8). The duration of
      follow-up was significantly longer for the no-repair group (p = 0.004), whereas
      baseline tear size was significantly larger in the repair group (p = 0.014). The
      percentage of patients requiring additional surgery was significantly higher in
      the no-repair group after adjustment for age, sex, duration of follow-up, and
      tear size (9.5% higher in estimated means between groups [95% confidence
      interval, 2.1% to 17%]; p = 0.012). The likelihood of a recurrent defect (repair
      group) or extension of the prior tear (no-repair group) was not different between
      groups after adjustment for age, sex, duration of follow-up, and tear size (p =
      0.4). There were no differences between the repair and no-repair groups in terms
      of the Constant score after adjustment for age, sex, duration of follow-up, and
      tear size (p = 0.31). The final tear size was significantly larger in the no
      repair group than the repair group (967 mm2 higher in estimated means between
      groups [95% confidence interval, 771 to 1,164 mm2]; p < 0.001). Conclusions: At
      intermediate to long-term follow-up, rotator cuff repair was associated with
      decreased final tear size and decreased need for future surgery after adjusting
      for age, sex, duration of follow-up, and tear size. The likelihood of a recurrent
      defect after rotator cuff repair did not differ from that of tear extension after
      nonoperative treatment. Thus, rotator cuff repair may not alter natural history.
      Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 30229237
TI  - Iliopsoas Disorder in Athletes with Groin Pain: Prevalence in 638 Consecutive
      Patients Assessed with MRI and Clinical Results in 134 Patients with Signal
      Intensity Changes in the Iliopsoas.
AB  - Background: Although iliopsoas disorder is one of the most frequent causes of
      groin pain in athletes, little is known about its prevalence and clinical impact.
      Methods: We retrospectively reviewed the cases of 638 consecutive athletes who
      had groin pain. Each athlete was assessed with magnetic resonance imaging (MRI).
      First, we identified the prevalence of changes in signal intensity in the
      iliopsoas. Then we classified the changes in signal intensity in the iliopsoas,
      as visualized on short tau inversion recovery MRI, into 2 types: the muscle
      strain type (characterized by a massive high-signal area in the muscle belly,
      with a clear border) and the peritendinitis type (characterized by a long and
      thin high-signal area extending proximally along the iliopsoas tendon from the
      lesser trochanter, without a clear border). Finally, we compared the time to
      return to play for the athletes who had these signal intensity changes. Results:
      Changes in signal intensity in the iliopsoas were detected in 134 (21.0%) of the
      638 athletes. According to our MRI classification, 66 athletes had peritendinitis
      changes and 68 had muscle-strain changes. The time from the onset of groin pain
      to return to play was significantly shorter for the patients with muscle-strain
      changes on MRI than for those with peritendinitis changes (8.6 +/- 8.3 versus
      20.1 +/- 13.9 weeks, respectively; p < 0.0001). Conclusions: Changes in MRI
      signal intensity in the iliopsoas were observed in 21.0% of 638 athletes who had
      groin pain. Distinguishing between muscle-strain changes and peritendinitis
      changes could help to determine the time to return to play.

PMID- 30229238
TI  - Preoperative Skin-Surface Cultures Can Help to Predict the Presence of
      Propionibacterium in Shoulder Arthroplasty Wounds.
AB  - Background: Propionibacterium species are commonly cultured from specimens
      harvested at the time of revision shoulder arthroplasty. These bacteria reside in
      normal sebaceous glands, out of reach of surgical skin preparation. The
      arthroplasty incision transects these structures, which allows Propionibacterium
      to inoculate the wound and to potentially lead to the formation of a biofilm on
      the inserted implant. To help identify patients who are at increased risk for
      wound inoculation, we investigated whether preoperative cultures of the specimens
      from the unprepared skin surface were predictive of the results of intraoperative
      cultures of dermal wound-edge specimens obtained immediately after incision of
      the surgically prepared skin. Methods: Sixty-six patients (mean age, 66.1 +/- 9.4
      years [range, 37 to 82 years]; 73% male) undergoing primary shoulder arthroplasty
      had preoperative cultures of the unprepared skin surface and intraoperative
      cultures of the freshly incised dermis using special culture swabs. For the first
      50 patients, a control swab was opened to air during the same time that the
      dermal specimen was obtained. The results for female and male patients were
      characterized as the Specimen Propionibacterium Value (SpPV). We then determined
      the degree to which the results of cultures of the skin surface specimens were
      predictive of the results of culture of the dermal specimens. Results: The skin
      surface SpPV was >=1 in 3 (17%) of the 18 female patients and 34 (71%) of the 48
      male patients (p < 0.001). The dermal SpPV was >=1 in 0 (0%) of the 18 female
      patients and 19 (40%) of the 48 male patients (p < 0.001). None of the control
      samples had an SpPV of >=1. The predictive characteristics of a skin-surface SpPV
      of >=1 for a dermal SpPV of >=1 were as follows: sensitivity, 1.00 (95%
      confidence interval [CI], 0.82 to 1.00); specificity, 0.62 (95% CI, 0.46 to
      0.75); positive predictive value, 0.51 (95% CI, 0.34 to 0.68); and negative
      predictive value, 1.00 (95% CI, 0.88 to 1.00). Conclusions: A preoperative
      culture of the unprepared skin surface can help to predict whether the freshly
      incised dermal edge is likely to be positive for Propionibacterium. This test may
      help to identify patients who may merit more aggressive topical and systemic
      antibiotic prophylaxis. Clinical Relevance: This study shows that surgeons have
      the opportunity to use preoperative skin cultures to determine the likelihood
      that the shoulder arthroplasty wound will be culture-positive for
      Propionibacterium.

PMID- 30229239
TI  - Nitrogen-free commercial carbon cloth with rich defects for electrocatalytic
      ammonia synthesis under ambient conditions.
AB  - Nitrogen-free commercial carbon cloth treated at 450  degrees C in air possesses
      abundant defects, exhibiting superior electrocatalytic activity for the nitrogen
      reduction reaction (NRR) with an NH3 yield of 2.59 * 10-10 mol cm-2 s-1 and a
      Faradaic efficiency of 6.92% at -0.3 V (vs. RHE) in 0.1 M Na2SO4 + 0.02 M H2SO4.

PMID- 30229240
TI  - A pressure-driven gas-diffusion/permeation micropump for self-activated sample
      transport in an extreme micro-environment.
AB  - The micropump is the most important functional unit of a micro total analysis
      system (MUTAS). An ideal microfluidics system should adopt simple, stable,
      robust, inexpensive, and integrated on-chip strategies to transport samples for
      downstream applications, with little or no external energy consumption and
      limited manual intervention. Nevertheless, it remains a key challenge for
      traditional micropumps to be directly integrated into self-contained and
      disposable MUTAS for velocity-stable and passive sample transport. The best way
      to assess the capability of passive micropumps is to evaluate their pumping
      performance in extreme environments, e.g. a 3D configurated microchannel instead
      of a 2D configuration, high temperature conditions instead of at room
      temperature, a long microchannel instead of short microchannel, a complex
      topological microsystem (e.g. a microvascular network interconnecting multiple
      inlets and outlets) instead of a simple topological microsystem (e.g. a one
      directional microchannel connecting only one inlet and one outlet), and multi
      phase microdroplet transport instead of single-phase plug transport. In this
      review, a novel micropumping methodology - a pressure-driven gas
      diffusion/permeation micropump - is described, which is the first review paper
      dedicated to this subject. A comprehensive overview is provided for comparison
      between this novel micropumping methodology and traditional passive micropumps,
      especially for applications in stable velocity control in the aforementioned
      extreme environments. Compared with mainstream conventional micropumps, we
      confirm that pressure-driven gas-diffusion/permeation micropumps combine a number
      of superior properties all into one device, such as small size, simple structure,
      without the need for microfabrication procedures or external power consumption,
      strong transport capacity, homogeneous flow velocity, delivery capacity for both
      multi-phase microdroplets and single-phase plugs, long-distance transport,
      persistent pumping for both 3D microchannels and complex topological microsystems
      (e.g. a biomimetic microvasculature), low cost, ease of microdevice integration,
      bubble suppression and amazing stability at high temperatures. An advanced
      outlook and perspectives for the future development of this novel micropump are
      also discussed, which may serve as a starting point for researchers in the
      microfluidics fields to harness pressure-driven gas-diffusion/permeation
      micropumps for downstream applications.

PMID- 30229241
TI  - Remarkably high catalyst efficiency of a disilaruthenacyclic complex for
      hydrosilane reduction of carbonyl compounds.
AB  - A disilaruthenacyclic complex (1) showed extremely high catalytic activity for
      hydrosilane reduction of aldehydes and ketones to silyl ethers and secondary and
      tertiary amides to the corresponding amines. An sigma-CAM mechanism was proposed
      to explain the activity.

PMID- 30229243
TI  - Atomistic dewetting mechanics of Wenzel and monostable Cassie-Baxter states.
AB  - Water adhesion underlies wettabilities, and thus hydrophobicities, and defines
      surface properties like self-cleaning, icephobicity and many others. The
      nanomechanics of water adhesion, especially in the dynamic dewetting processes,
      has not been fully investigated. Here in this article, atomistic modeling and
      molecular dynamics simulations were utilized to probe the adhesion mechanics of
      water droplets on nanopillars and flat surfaces, covering dewetting in the Wenzel
      and the newly discovered monostable Cassie-Baxter states. The simulations were
      able to identify intermediate dewetting states on rough surfaces, and resolve the
      transition between wetting states under force. The results revealed
      characteristic features of dynamic water adhering stress underpinning dewetting
      on the nanoscale, which provided deeper knowledge on surface dewetting mechanics.
      This work complements nanoscale dewetting experiments for new fundamental
      insights in studies including nanoroughness design, enhanced oil recovery, anti
      icing and others.

PMID- 30229242
TI  - Internalization of the pseudorabies virus via macropinocytosis analyzed by
      quantum dot-based single-virus tracking.
AB  - With the aid of the single-virus tracking technique and the quantum dot-labeling
      strategy, the internalization of the pseudorabies virus (PrV) has been visualized
      in real time. The results demonstrate that macropinocytosis can be considered as
      a major pathway for PrV entering HeLa cells, which facilitates the development of
      therapeutics for virus-triggered diseases.

PMID- 30229244
TI  - Post Hartree-Fock calculations of pnictogen-uranium bonding in EUF3 (E = N-Bi).
AB  - NUF3 is identified as having a N[triple bond, length as m-dash]U triple bond, as
      has been previously found (Andrews et al., Angew. Chem. Int. Ed., 2008, 47,
      5366). By contrast, while previously reported calculations on PUF3 and AsUF3
      (Andrews et al., Inorg. Chem., 2009, 48, 6594) gave a E[triple bond, length as m
      dash]U triple bond, our calculations suggest a single bond for both molecules,
      with antibonding pi* and non-bonding 5fU orbitals significantly occupied, and
      highly multiconfigurational wavefunctions. We propose this difference to be due
      to the smaller [6,6] active space used (sigma, pi, pi* and sigma*) in the
      previous studies. In our calculations, a [6,16] active space was employed in
      order to include uranium f-orbitals and pnictogen d-orbitals.

PMID- 30229246
TI  - Intermolecular interactions upon carbon dioxide capture in deep-eutectic
      solvents.
AB  - Herein we report the CO2 uptake in potential deep-eutectic solvents (DESs) formed
      between hydrogen bond acceptors (HBAs) such as monoethanolammonium chloride
      ([MEA.Cl]), 1-methylimidazolium chloride ([HMIM.Cl]) and tetra-n-butylammonium
      bromide ([TBAB]) and hydrogen bond donors (HBDs) like ethylenediamine ([EDA]),
      diethylenetriamine ([DETA]), tetraethylenepentamine ([TEPA]),
      pentaethylenehexamine ([PEHA]), 3-amino-1-propanol ([AP]) and
      aminomethoxypropanol ([AMP]) and analyzed the outcome in terms of the specific
      polarity parameters. Among various combinations of HBAs and HBDs, [MEA.Cl][EDA]-,
      [MEA.Cl][AP]-, [HMIM.Cl][EDA]- and [HMIM.Cl][AP] showed excellent CO2 uptake
      which was further improved upon increasing the mole ratio of HBA : HBD from 1 : 1
      to 1 : 4. The lowest CO2 uptake in [MEA.Cl][PEHA] (12.7 wt%) and [HMIM.Cl][PEHA]
      (8.4 wt%) despite the highest basicity of [PEHA] infers that the basicity is not
      the sole criteria for guiding the CO2 uptake but, in reality, CO2 capture in a
      DES relies on the interplay of H-bonding interactions between each HBA and HBD.
      The role of HBAs in guiding CO2 uptake was more prominent with weak HBDs such as
      [TEPA] and [PEHA]. The speciation of absorbed CO2 into carbamate, carbonate, and
      bicarbonate was favorable in DES characterized by comparable hydrogen bond donor
      acidity (alpha) and hydrogen bond acceptor basicity (beta) values, whereas the
      conversion of carbamate to carbonate/bicarbonate was observed to depend on alpha.
      The addition of water in DES resulted in lower CO2 uptake due to the decreased
      basicity (beta).

PMID- 30229247
TI  - Analysis of human menisci degeneration via infrared attenuated total reflection
      spectroscopy.
AB  - Degeneration of human meniscal tissue induces impairment of normal knee
      functions, and is a highly relevant etiology of knee joint tears and
      osteoarthritis. Currently, the grading scale of meniscus degeneration is
      conventionally derived from evaluating meniscal morphology and histological
      staining. However, mid-infrared attenuated total reflectance (IR-ATR)
      spectroscopy is a particularly useful technique that may analyze the biomolecular
      composition at a sample surface, and provide information on the intra- and/or
      inter-molecular chemical bonds. In the present study, 61 lyophilized human
      menisci samples at different grades of degeneration were analyzed via IR-ATR
      spectroscopy in a label-free fashion, and the data were evaluated via Gaussian
      peak fitting and 2D correlation analysis. During increasing meniscal degeneration
      (i.e., grade 1 to 4) along with calcification at grade 4, an evident blue shift
      of the amide I band (1700-1600 cm-1) was observed in the associated IR spectra.
      In addition, Gaussian peak fitting revealed significant area variance of the
      fitted sub-peaks. 2D correlation spectra provided further access to detailed
      changes of the amide I band during the degeneration process. Derived from this
      multi-tiered data analysis taking into account the protein secondary structure
      information within the amide I band, and the triple helical structure of meniscal
      collagen, the blue shift and peak area changes during meniscus degeneration are
      indicative of collagen fibril formation during evolving degeneration.
      Furthermore, a degradation of the water-binding proteoglycan and collagen network
      especially for degenerated menisci with calcification was observed. Results were
      compared with a collagen-chondroitin sulphate mixture model, confirming the
      observed changes in collagen fibrils and proteoglycans. In summary, this study
      confirms the utility of IR-ATR spectroscopy as a versatile tool providing access
      to meniscal tissue degeneration processes at molecular level detail, and may in
      future evolve into a useful diagnostic instrument for analyzing cartilage
      degeneration.

PMID- 30229245
TI  - Enzyme-immobilized metal-organic framework nanosheets as tandem catalysts for the
      generation of nitric oxide.
AB  - An enzyme-immobilized metal-organic framework (MOF) nanosheet system was
      developed as a tandem catalyst, which converted glucose into gluconic acid and
      H2O2, and sequentially the latter could be used to catalyze the oxidation of l
      arginine to generate nitric oxide in the presence of porphyrinic MOFs as
      artificial enzymes under physiological pH, showing great potential in cancer
      depleting glucose for starving-like/gas therapy.

PMID- 30229248
TI  - Wirelessly activated device with an integrated ionic polymer metal composite
      (IPMC) cantilever valve for targeted drug delivery.
AB  - This paper reports a wirelessly powered ionic polymer-metal composite (IPMC) soft
      actuator operated by external radio frequency (RF) magnetic fields for targeted
      drug delivery. A 183 MUm thick IPMC cantilever valve was fitted with an embedded
      LC resonant circuit to wirelessly control the actuator when the field frequency
      is tuned to its resonant frequency of approximately 25 MHz. Experimental
      characterization of the fabricated actuator showed a cumulative cantilever
      deflection of 160 MUm for three repeated RF ON-OFF cycles at 0.6 W input power.
      The device was loaded with a dye solution and immersed in DI water to demonstrate
      wireless drug release. The qualitative result shows the successful release of the
      dye solution from the device reservoir. The release rate can be controlled by
      tuning the RF input power. We achieved a maximum average release rate of ~0.1 MUl
      s-1. We further conducted an in vitro study with human tumor cells (HeLa) to
      demonstrate the proof of concept of the developed device. The experiments show
      promising results towards the intended drug delivery application.

PMID- 30229249
TI  - Dynamics of nanointerfaces: general discussion.

PMID- 30229250
TI  - Preparation and identification of novel inhibitory angiotensin-I-converting
      enzyme peptides from tilapia skin gelatin hydrolysates: inhibition kinetics and
      molecular docking.
AB  - Tilapia skin gelatin was hydrolyzed by successive simulated gastrointestinal
      digestion, and the hydrolysates were further separated by transport across a Caco
      2 cell monolayer. Angiotensin-I-converting enzyme inhibitory (ACEI) peptides were
      separated by successive chromatographic steps from the transport hydrolysates. We
      have identified two key ACEI peptides, namely VGLPNSR (741.4133 Da) and QAGLSPVR
      (826.4661 Da) with IC50 values of ACEI activity of 80.90 and 68.35 MUM,
      respectively. Lineweaver-Burk plots indicated that the inhibitory ACE kinetics of
      the two peptides were noncompetitive. Molecular docking simulation showed that
      the two peptides could interact with the ACE site via hydrogen bonds with high
      binding power. However, the hydrogen bonds were not formed with the key amino
      acid residues in the active site of ACE. This finding was in accordance with the
      noncompetitive inhibition. This study established a novel approach to identify
      key ACEI peptides and suggested the use of tilapia peptides as functional food
      ingredients to prevent hypertension.

PMID- 30229251
TI  - Structural insights and influence of V599 mutations on the overall dynamics of
      BRAF protein against its kinase domains.
AB  - Mutations in the BRAF gene are well known for their oncogenic effects. Point
      mutations in V599 are particularly oncogenic and are considered important for
      therapeutic purposes. Along with wild type, other V599 mutated BRAF variants viz.
      V599E, V599D and V599R are reported and crystals of the former two with inhibitor
      (BAY43-9006) are further detailed. Both wild-type and mutated BRAF forms show
      similar interaction patterns with BAY43-9006, but the 599th residue did not show
      any involvement in the interactions. Upon BAY43-9006 binding, kinase domains of
      both forms were found adopting essentially identical conformations. However,
      BAY43-9006 shows a varied activity profile in the case of the wild and V599E
      variant of the BRAF protein. Furthermore, MMGBSA binding energy results for all
      four BRAF variants, further revealed the importance of the 599th residue. In
      depth analysis viz. molecular dynamics, residue correlation studies and residue
      interaction network (RIN) analyses were conducted, providing a deep insight into
      the 599th residue and its impact on the overall dynamics of BRAF protein. Our
      findings reveal that the mutated residue at the 599th position not only changed
      the BAY43-9006-BRAF binding behaviour but also produced a massive impact on the
      overall dynamic behaviour of the protein. The insights obtained herein could be
      of great relevance for designing new BRAF inhibitors aimed at getting ideal
      activity against all BRAF forms.

PMID- 30229252
TI  - Benzylic C(sp3)-H bond sulfonylation of 4-methylphenols with the insertion of
      sulfur dioxide under photocatalysis.
AB  - Sulfonylation of the benzylic C-H bond is developed through a three-component
      reaction of aryldiazonium tetrafluoroborates, 4-methylphenols and sodium
      metabisulfite (Na2S2O5). The inorganic sulfite of sodium metabisulfite is used as
      the SO2 surrogate. In this transformation, benzylic C(sp3)-H bond sulfonylation
      is achieved in the presence of a photocatalyst under visible light. A radical
      pathway involving the arylsulfonyl radical and intermolecular hydrogen atom
      abstraction is proposed.

PMID- 30229253
TI  - A facile route to 1H- and 2H-indazoles from readily accessible acyl hydrazides by
      exploiting a novel aryne-based molecular rearrangement.
AB  - Herein we report the transformation of readily synthesised acyl hydrazides into 2
      hydrazobenzophenones via a novel molecular rearrangement pathway using aryne
      chemistry. The developed reaction protocol is performed under relatively mild
      conditions and is tolerant of a wide variety of functional groups, and the 2
      hydrazobenzophenone products provide access to both 1H- and 2H-indazoles from a
      single intermediate.

PMID- 30229254
TI  - Elucidating white light emissions in Tm3+/Dy3+ codoped polyoxometalates: a color
      tuning and energy transfer mechanism study.
AB  - The double-tartaric bridging Tm-substituted POM derivative
      [N(CH3)4]6K3H7[Tm(C4H2O6)(alpha-PW11O39)]2.27H2O (1) was successfully synthesized
      and well characterized by various physico-chemical analyses. Furthermore, the
      mixed Dy3+/Tm3+ ion-based POM derivatives [N(CH3)4]6K3H7[DyxTm1-x(C4H2O6)(alpha
      PW11O39)]2.27H2O (3-8) were first synthesized and confirmed by PXRD and IR
      spectra, indicating compounds 3-8 are isomorphic with 1. The detailed analyses of
      Ln-O-W bond angle and coordinated aqua ligands around emitting Ln3+ ions have
      revealed that the mentioned negative factors do not effectively affect the
      luminescence of emitting Ln3+ ions in 1-8. Investigations of PL emissions reveal
      that 3-8 can display color-tunable PL properties, emitting color from blue to
      white to yellow. The study of time-resolved emission spectroscopy of 6 indicates
      the energy can transfer from the LMCT excited state of POM fragments to Tm3+
      and/or Dy3+ ions. Furthermore, the decreased luminescent lifetime of Tm3+ ions in
      3-8 reasonably verifies the energy transfer from Tm3+ to Dy3+ ions to efficiently
      facilitate emissions of the Dy3+ centre.

PMID- 30229255
TI  - Remarkable difference in Al3+ and Zn2+ sensing properties of quinoline based
      isomers.
AB  - Two positional isomers, 4-methyl-2-((quinolin-6-ylimino)methyl)phenol (6-QMP) and
      4-methyl-2-((quinolin-2-ylimino)methyl)phenol (2-QMP), have been synthesized to
      compare their fluorescence sensing properties. 6-QMP and 2-QMP have been
      synthesized by Schiff-base condensation between 2-hydroxy-5-methylbenzaldehyde
      and the respective amine (6-aminoquinoline for 6-QMP and 2-aminoquinoline for 2
      QMP) under mild conditions. These compounds have been characterized by standard
      methods. 6-QMP and 2-QMP have been found to be dual fluorescence chemosensors for
      Al3+ and Zn2+ ions but the increment of fluorescence intensity varies. 6-QMP can
      detect Al3+ (emission at 543 nm) and Zn2+ (emission at 525 nm) by the enhancement
      of emission intensity by 97 and 79 fold, respectively, with the same excitation
      wavelength at 415 nm. However, 2-QMP shows two different excitation and emission
      wavelengths for the detection of Al3+ (emission at 376 nm; lambdaex = 330 nm) and
      Zn2+ (emission at 550 nm; lambdaex = 435 nm). The increase in emission intensity
      is low (4.5 fold for Al3+ and 35 fold for Zn2+) compared to that with 6-QMP. The
      enhancement of intensity may be explained by the PET mechanism. Both the probes
      form a 1 : 1 complex with both the metal ions as indicated by the elemental and
      different spectral analysis. 6-QMP shows better sensitivity towards both the
      metal ions than 2-QMP. Both the probes are able to detect Al3+ and Zn2+ ions by
      producing distinct color changes that can be observed by the naked eye. Some
      theoretical calculations have been performed to investigate spectral transitions
      of the probes along with their aluminum and zinc compounds. These compounds have
      been used for living cell imaging studies. A comparison with the recently
      published studies has been made.

PMID- 30229257
TI  - Pt NPs immobilized on a N-doped graphene@Al2O3 hybrid support as robust catalysts
      for low temperature CO oxidation.
AB  - Platinum nanoparticles (Pt NPs) immobilized on a N-doped graphene@Al2O3 hybrid
      support (Al2O3@CNx) were synthesized and employed for low temperature CO
      oxidation. The superior catalytic activity was attributed to a strong metal
      support interaction between Pt NPs and the N-doped graphene surface which was
      also confirmed in the direct dehydrogenation reaction.

PMID- 30229258
TI  - Homochiral coordination polymers constructed from V-shaped oxybisbenzoyl-based
      amino acid derivatives: structures, magnetic and photoluminescence properties.
AB  - Five novel homochiral coordination polymers (HCPs) [Cu2(ODBALa)2(bpa)2H2O].7H2O
      (1), [M(ODBALa)H2O].H2O (M = Mn for 2; Co for 3), [Cu(ODBPRo)(bpe)].7H2O (4) and
      [Cd2.5(ODBPRo)(HODBPRo)3(bpe)2.5].13H2O (5) have been successfully synthesized by
      using designed chiral 4,4'-oxybisbenzoyl alanine/proline derivatives in the
      absence/presence of N-donor ancillary ligands, where H2ODBALa = 4,4'
      oxybisbenzoyl-bis(l-alanine), H2ODBPRo = 4,4'-oxybisbenzoyl-bis(l-proline), bpa =
      1,2-bis(4-pyridyl)ethane, and bpe = 1,2-bis(4-pyridyl)ethene. Interestingly, the
      combination of the chiral derivatives and metal ions gives various chiral metal
      organic fragments, which are connected by N-donor ancillary ligands to construct
      the intriguing homochiral structures. In 1, 40-membered [Cu2(ODBALa)2]
      metallacycles as beads are strung by bpa ligands, yielding a one-dimension (1D)
      tortuous chain. Compounds 2 and 3 are isomorphous and possess a 3D metal-organic
      framework, embedding the unique (MU2-COO)(MU2-Ocarboxylate)(MU2-H2O) triple
      bridges and twisted (-Mn4(ODBALa)4-)n left-handed helical chains. In 4, the
      [Cu(ODBPRo)]n left-handed helical chains are linked by bpe ligands to constitute
      a high undulated 2D layer. In 5, the crab-like
      [(Cd1)2(Cd2)(Cd3)2(HODBPRo)6(ODBPRo)2] fragments are joined together to form a 1D
      left-handed helical chain, which is further connected by bpe ligands to build a
      remarkable layered network. Magnetic susceptibility measurements of 2 and 3
      indicate typical antiferromagnetic behaviour between the triple-bridging Mn(ii)
      ions in 2, whereas ferromagnetic coupling between the triple-bridging Co(ii) ions
      exists in 3. Moreover, the photoluminescent spectrum of 5 exhibits a strong solid
      state emission at 414 nm.

PMID- 30229260
TI  - Tri- and hexa-nuclear NiII-MnII complexes of a N2O2 donor unsymmetrical ligand:
      synthesis, structures, magnetic properties and catalytic oxidase activities.
AB  - A new mononuclear Ni(ii) complex, [NiL] (1) of an unsymmetrically dicondensed
      N2O2 donor ligand, H2L (where H2L = N-alpha-methylsalicylidene-N'-salicylidene
      1,3-propanediamine), has been synthesized. Complex 1, on reaction with Mn(ii) in
      the presence of different co-anions, yielded three heterometallic NiII-MnII
      complexes, [(NiL)2Mn(NCS)2].CH3CN (2), [(NiL)2Mn(N3)(H2O)](ClO4).H2O (3) and
      [{(NiL)2Mn(H2O)}2(MU1,3-N3)](ClO4)3 (4). Single crystal structural analyses show
      that complexes 2 and 3 contain similar bent trinuclear NiII2MnII structures, with
      the difference that in complex 2 two SCN- ions and in 3, one N3- and one H2O
      molecule are coordinated to the Mn(ii) centre. Complex 4 possesses a hexanuclear
      structure, in which two trinuclear NiII2MnII units are connected via a single
      MU1,3-azido bridge. Variable temperature dc molar magnetic susceptibility
      measurements reveal that the two Mn(ii) centres in complex 4 are
      antiferromagnetically coupled with an exchange coupling constant (J) of -3.73 cm
      1. Among the three heterometallic complexes, only 3 and 4 show bio-mimetic
      catalytic oxidase activities. For catecholase like activity, the turnover numbers
      (Kcat) of complexes 3 and 4 are 984 and 2081 h-1, respectively, whereas for
      phenoxazinone synthase-like activity, the turnover numbers of complexes 3 and 4
      are 6351 and 10 545 h-1, respectively. The high catalytic oxidase activities of
      complexes 3 and 4 in contrast to the inactivity of complex 2 are attributed to
      the coordination of a water molecule to the Mn(ii) centre in the former
      structures, which facilitates the binding of the substrate with the catalyst.
      Mass spectral analyses suggest the probable formation of a complex-substrate
      intermediate in these catalytic reactions and cyclic voltammetry measurements
      show that Ni(ii) is reducible to Ni(i).

PMID- 30229259
TI  - Towards rational design of RAD51-targeting prodrugs: platinumIV-artesunate
      conjugates with enhanced cytotoxicity against BRCA-proficient ovarian and breast
      cancer cells.
AB  - Two PtIV-artesunate anticancer prodrugs that target RAD51, a crucial protein in
      homologous recombination mediating the sensitivity of cancer cells to DNA
      damaging agents, were designed; their cytotoxicities against BRCA-proficient
      ovarian and breast cancer cells are significantly higher than those of cisplatin.

PMID- 30229264
TI  - Metallothionein diversity and distribution in the tree of life: a multifunctional
      protein.
AB  - MTs are small cysteine-rich proteins that chelate metal ions such as Cu+ and
      Zn2+, and are widely distributed in several life domains, in particular the
      eukaryotic one. They are present in the following phyla: Opisthokonta (mainly
      Fungi and Metazoa), Chloroplastida, Alveolata (ciliates) and Excavata
      (Trichomonas) for Eukaryota and Cyanobacteria, Actinobacteria, Proteobacteria and
      Firmicutes for Bacteria. However, their absence in some phyla underlines that MTs
      are far from being fully known. The MT amino acid sequences show a great
      diversity of sizes and structures both in terms of cysteine motifs and
      organization of these motifs. This review also highlights the different oxidized,
      apoprotein and metalated forms of MTs, the diversity of interactions they can
      establish with different molecules and their central and multifunctional cellular
      role. We present MTs as a protein system that could be a hub in molecular
      interaction networks. Studying MTs as a hub in cellular interaction networks
      should provide new insights for a better understanding of MT functioning and
      cellular processes.

PMID- 30229266
TI  - Fast-growing Painful Leg Ulcers in a 26-year-old Woman with Systemic Lupus
      Erythematosus: A Quiz.

PMID- 30229267
TI  - Some strains that have converged to infect Prunus spp. trees are members of
      distinct Pseudomonas syringae genomospecies and ecotypes as revealed by in silico
      genomic comparison.
AB  - A complementary taxonomic and population genetic study was performed to delineate
      genetically and ecologically distinct species within the Pseudomonas syringae
      complex by assessing 16 strains including pathovar strains that have converged to
      infect Prunus spp. trees, and two outgroups. Both average nucleotide identity and
      genome-to-genome distance comparison methods revealed the occurrence of distinct
      genomospecies, namely 1, 2, 3 and 8 (sensu Gardan et al.), with the latter two
      being closely related. Strains classified as P. s. pv. morsprunorum clustered
      into two distinct genomospecies, namely 2 and 8. Both the AdaptML and
      hierarchical Bayesian analysis of population structure methods highlighted the
      presence of three ecotypes, and the taxonomically related genomospecies 3 and 8
      strains were members of the same ecotype. The distribution of pathogenic and
      virulence-associated genetic traits among Pseudomonas strains did not reveal any
      distinct type III secretion system effector or phytotoxin distribution pattern
      that characterized single genomospecies and strains that infect Prunus spp. The
      complete WHOP (Woody HOst and Pseudomonas spp.) genomic region and the entire
      beta-ketoadipate gene cluster, including the catBCA operon, were found only in
      the members of genomospecies 2 and in the two P. s. pv. morsprunorum strains of
      genomospecies 8. A reduced gene flow between the three ecotypes suggested that
      point mutations played a larger role during the evolution of the strains than
      recombination. Our data support the idea that Prunus trees can be infected by
      different strains of distinct Pseudomonas genomospecies/ecotypes through diverse
      mechanisms of host colonization and infection. Such strains may represent
      particular lineages that emerged from environments other than that of the
      infected plant upon acquiring genetic traits that gave them the ability to cause
      plant diseases. The complementary assessment of bacterial strains using both
      taxonomic approaches and methods that reveal ecologically homogeneous populations
      has proven useful in confirming the cohesion of bacterial clusters.

PMID- 30229268
TI  - [An incidental finding].

PMID- 30229269
TI  - Outcomes after laparoscopic removal of retropubic midurethral slings for chronic
      pain.
AB  - INTRODUCTION AND HYPOTHESIS: Midurethral slings (MUS) are an established
      treatment for stress urinary incontinence (SUI), with good objective outcomes and
      low rates of complications. However, large population-based registry studies
      highlighted long-term complications from polypropylene slings including erosion,
      dyspareunia and chronic pain. With recent highly negative media coverage, many
      women are presenting with chronic pain attributed to the mesh to request complete
      removal. The available literature provides limited evidence on safety, symptom
      resolution and incontinence following MUS removal. METHODS: We identified all
      patients who underwent laparoscopic removal of MUS mesh at our hospital between
      2011 and 2016. We extracted data from medical records to assess operative safety
      and contacted all patients by questionnaire that incorporated pain scales,
      symptom severity and satisfaction. RESULTS: A total of 56 women were assessed.
      Removal occurred at a median of 44 months following sling insertion (range 3
      192). Mean operative time was 74 min (range 44-132). Two patients were returned
      to theatre (one at 24 hours and one at 14 days) to evacuate a retropubic
      haematoma, but no visceral injuries occurred. The median inpatient stay was 2
      days (range 1-7). Of the 46% of patients who returned the questionnaire (n = 26),
      88% said they would recommend the procedure. There was a median 6-point decrease
      in pain scores (10-point numerical scale, p < 0.0001); 44.6% reported worsening
      SUI, more common with removal of the suburethral mesh [odds ratio (OR) 10.72 95%
      confidence interval (CI) 1.10-104]. CONCLUSIONS: Laparoscopic removal of MUS is
      feasible and effective but carries a risk of worsening SUI.

PMID- 30229270
TI  - Quantitative assessment of mesorectal fat: new prognostic biomarker in patients
      with mid-to-lower rectal cancer.
AB  - OBJECTIVES: To investigate the impact of mesorectal fat area (MFA) on oncologic
      outcomes in patients with mid-to-lower rectal cancer who received curative-intent
      surgery. METHODS: Patients with mid-to-lower rectal cancer who underwent
      preoperative abdominopelvic computed tomography (CT) and curative-intent surgery
      in 2011 were divided into two groups by tumour recurrence (group A) or no
      recurrence (group B) during a 5-year follow-up. Visceral fat area (VFA) and MFA
      were measured on preoperative CT and cutoff values were calculated using the
      Youden index. Univariate and multivariate regression analyses including BMI, VFA,
      and MFA were performed to investigate meaningful prognostic biomarkers. The
      Kaplan-Meier method with log-rank testing was used to validate prognostic
      biomarkers. RESULTS: Group A contained 42 patients and group B had 155 patients.
      Cutoff values were 25 kg/m2 for BMI, 130 cm2 for VFA, and 10 cm2 for MFA using
      the Youden index. On multivariate Cox regression analysis, MFA (odds ratio [OR] =
      0.426, p = 0.010), TNM stage (p = 0.027), and perioperative complication grade (p
      = 0.028) were significantly different between groups. BMI and VFA did not show
      significant differences. By the Kaplan-Meier method with log-rank testing,
      disease-free survival (DFS) was significantly longer in patients with MFA >=10
      cm2 compared to patients with MFA <10 cm2 (p = 0.021), with no significant
      difference in overall survival (OS). CONCLUSIONS: MFA was an independent
      biomarker for predicting DFS in patients who underwent curative-intent surgery
      for mid-to-lower rectal cancer. KEY POINTS: * Mesorectal fat area is associated
      with the prognosis of rectal cancer patients. * Mesorectal fat area can be
      calculated easily in pre-operative CT scan. * Predicting prognosis of the cancer
      patient before operation is important.

PMID- 30229271
TI  - Background parenchymal enhancement in pregnancy-associated breast cancer: a
      hindrance to diagnosis?
AB  - PURPOSE: The purpose of this study is to investigate the detectability of
      pregnancy-associated breast cancer (PABC) in lactating glandular tissue on
      magnetic resonance imaging (MRI) by using pre- and post-contrast acquisitions and
      their derived postprocessed images and compare these results to ultrasound (US)
      and mammography (MG). MATERIALS AND METHODS: We reviewed the electronic database
      for women with PABC and existing breast MRI. MR images (T2-weighted short
      inversion-recovery sequence [STIR], dynamic contrast-enhanced T1-weighted
      gradient echo sequence and postprocessed subtraction images [early post-contrast
      minus pre-contrast]) were retrospectively evaluated (image quality,
      parenchymal/tumour enhancement kintetics, tumour size and additional lesions).
      Supplemental subtraction images (latest post-contrast minus early post-contrast)
      to reduce plateau enhancement were additionally calculated and tumour conspicuity
      and size were measured. Findings were compared to US and MG reports. RESULTS:
      Nineteen patients (range 27-42 years) were included. Background parenchymal
      enhancement (BPE) was minimal (n=1), mild (n=3), moderate (n=7) and marked (n=8)
      with kinetics measured plateau (n=8), continuous (n=10) and not quantifiable
      (n=1). Tumour kinetics presented wash-out (n=17) and plateau (n=2). Eighteen of
      nineteen tumours were identified on the supplemental subtraction images. All
      tumours were visible on US; 12/19 were visible on MG (63.2%). MRI detected
      additional malignant lesions in two patients. CONCLUSION: Despite high BPE of the
      lactating breast, MRI securely detects carcinomas and identifies satellite
      lesions. By using supplemental subtraction images, background enhancement can be
      eliminated to facilitate diagnosis. US remains a reliable diagnostic tool, but
      additional MRI is recommended to rule out satellite/contralateral lesions. MG
      interpretations can be difficult due to high parenchymal density. KEY POINTS: *
      Despite high background enhancement, MRI of the breast confidently detects
      carcinomas and identifies further lesions in the lactating breast. * By using
      supplemental subtraction images, background enhancement in the lactating breast
      can be eliminated to facilitate diagnosis. * US remains a reliable diagnostic
      tool. Mammography can be limited due to extremely dense breast tissue related to
      lactation.

PMID- 30229273
TI  - Dose-dependent effect of smoking on risk of coronary heart disease, heart failure
      and stroke in individuals with type 1 diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess the potential dose-dependent
      effects of smoking on the risk of CHD, heart failure and stroke in individuals
      with type 1 diabetes. METHODS: The study included 4506 individuals with type 1
      diabetes who were participating in the Finnish Diabetic Nephropathy (FinnDiane)
      study. Intensity of smoking was estimated by packs per day and cumulative smoking
      by pack-years. Cox regression analyses were used to estimate the risk of incident
      CHD, heart failure or stroke during follow-up. RESULTS: One pack per day
      significantly increased the risk of incident CHD in current smokers compared with
      never smokers (HR 1.45 [95% CI 1.15, 1.84]), after adjustment for age, sex,
      HbA1c, hypertension, duration of diabetes and BMI. The risk of CHD in former
      smokers was similar to the risk in never smokers. The risk of incident heart
      failure was 1.43 (95% CI 1.03, 1.97) in current smokers per one pack per day and
      1.37 (95% CI 1.05, 1.77) in former smokers, while the risk of incident stroke was
      1.70 (95% CI 1.26, 2.29) and 1.49 (95% CI 1.14, 1.93), respectively. After
      further adjustments for lipids, however, the difference in the risk of heart
      failure in current and former smokers was no longer significant. Cumulative
      smoking data were similar to smoking intensity data. CONCLUSIONS/INTERPRETATION:
      There is a dose-dependent association between smoking and cardiovascular disease
      in individuals with type 1 diabetes. In men in particular, the risk of incident
      stroke remains high even after smoking cessation and is increased in current and
      former smokers independently of other risk factors.

PMID- 30229272
TI  - Targeting senescence to delay progression of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic and often progressive, demyelinating disease
      of the central nervous system (CNS) white and gray matter and the single most
      common cause of disability in young adults. Age is one of the factors most
      strongly influencing the course of progression in MS. One of the hallmarks of
      aging is cellular senescence. The elimination of senescent cells with senolytics
      has very recently been shown to delay age-related dysfunction in animal models
      for other neurological diseases. In this review, the possible link between
      cellular senescence and the progression of MS is discussed, and the potential use
      of senolytics as a treatment for progressive MS is explored. Currently, there is
      no cure for MS and there are limited treatment options to slow the progression of
      MS. Current treatment is based on immunomodulatory approaches. Various cell types
      present in the CNS can become senescent and thus potentially contribute to MS
      disease progression. We propose that, after cellular senescence has indeed been
      shown to be directly implicated in disease progression, administration of
      senolytics should be tested as a potential therapeutic approach for the treatment
      of progressive MS.

PMID- 30229275
TI  - Effects of Wind Mixing in a Stratified Water Column on Toxic Cyanobacteria and
      Microcystin-LR Distribution in a Subtropical Reservoir.
AB  - We analyzed the effects of stratification changes due to wind on the vertical
      cyanobacteria distribution and microcystin-LR concentrations in a reservoir and
      assessed the implications for water management. Under stratified conditions, the
      highest microcystin concentrations (up to 4.16 ug/L) and toxic cyanobacteria
      biovolume occurred in the epilimnion (~ 1 m). The lowest microcystin
      concentrations were between 0.02 and 1.28 ug/L and occurred in the hypolimnion (~
      20 m). A cold front passage associated with high wind velocities induced water
      column mixing, promoting the redistribution of microcystin-LR and cyanobacteria
      throughout the water column and increasing their concentrations in deeper zones.
      Microcystin-LR concentration was positively correlated with cyanobacteria
      biovolume (r = 0.747) and chlorophyll a concentration (r = 0.798). Changes in
      thermal profile due to wind would imply a greater challenge for drinking water
      treatment plants, since high cyanobacterial and microcystin concentrations could
      reach deep-water intakes.

PMID- 30229274
TI  - A UK nationwide prospective study of treatment change in MODY: genetic subtype
      and clinical characteristics predict optimal glycaemic control after
      discontinuing insulin and metformin.
AB  - AIMS/HYPOTHESIS: Treatment change following a genetic diagnosis of MODY is
      frequently indicated, but little is known about the factors predicting future
      treatment success. We therefore conducted the first prospective study to
      determine the impact of a genetic diagnosis on individuals with GCK-, HNF1A- or
      HNF4A-MODY in the UK, and to identify clinical characteristics predicting
      treatment success (i.e. HbA1c <=58 mmol/mol [<=7.5%]) with the recommended
      treatment at 2 years. METHODS: This was an observational, prospective, non
      selective study of individuals referred to the Exeter Molecular Genetic
      Laboratory for genetic testing from December 2010 to December 2012. Individuals
      from the UK with GCK- or HNF1A/HNF4A-MODY who were not on recommended treatment
      at the time of genetic diagnosis, and who were diagnosed below the age of 30
      years and were currently aged less than 50 years, were eligible to participate.
      RESULTS: A total of 44 of 58 individuals (75.9%) changed treatment following
      their genetic diagnosis. Eight individuals diagnosed with GCK-MODY stopped all
      diabetes medication without experiencing any change in HbA1c (49.5 mmol/mol
      [6.6%] both before the genetic diagnosis and at a median of 1.25 years' follow-up
      without treatment, p = 0.88). A total of 36 of 49 individuals (73.5%) diagnosed
      with HNF1A/HNF4A-MODY changed treatment; however, of the 21 of these individuals
      who were being managed with diet or sulfonylurea alone at 2 years, only 13 (36.1%
      of the population that changed treatment) had an HbA1c <=58 mmol/mol (<=7.5%).
      These individuals had a shorter diabetes duration (median 4.6 vs 18.1 years),
      lower HbA1c (58 vs 73 mmol/mol [7.5% vs 8.8%]) and lower BMI (median 24.2 vs 26.0
      kg/m2) at the time of genetic diagnosis, compared with individuals (n = 23/36)
      with an HbA1c >58 mmol/mol (>7.5%) (or <58 mmol/mol [<7.5%] on additional
      treatment) at the 2 year follow-up. Overall, 64% (7/11) individuals with a
      diabetes duration of <=11 years and an HbA1c of <=69 mmol/mol (<=8.5%) at time of
      the genetic test achieved good glycaemic control (HbA1c <=58 mmol/mol [<=7.5%])
      with diet or sulfonylurea alone at 2 years, compared with no participants with a
      diabetes duration of >11 years and an HbA1c of >69 mmol/mol (>8.5%) at the time
      of genetic diagnosis. CONCLUSIONS/INTERPRETATION: In participants with GCK-MODY,
      treatment cessation was universally successful, with no change in HbA1c at follow
      up. In those with HNF1A/HNF4A-MODY, a shorter diabetes duration, lower HbA1c and
      lower BMI at genetic diagnosis predicted successful treatment with
      sulfonylurea/diet alone, supporting the need for early genetic diagnosis and
      treatment change. Our study suggests that, in individuals with HNF1A/HNF4A-MODY
      with a longer duration of diabetes (>11 years) at time of genetic test, rather
      than ceasing current treatment, a sulfonylurea should be added to existing
      therapy, particularly in those who are overweight or obese and have a high HbA1c.

PMID- 30229277
TI  - Evaluation of the Relevance of Myriophyllum alterniflorum (Haloragaceae) Cadmium
      Sensitive Biomarkers for Ecotoxicological Surveys.
AB  - Toxicity caused by trace metal elements in water is a major concern, leading to
      environmental disturbances and public health problems. The effect of cadmium on
      clonal macrophyte populations is poorly documented despite its high level of
      toxicity among aquatic organisms. Our aim here is to highlight the strong
      relationship existing between the physiological responses of Myriophyllum
      alterniflorum and the cadmium level over a long exposure period. Nine potential
      biomarkers of cadmium stress are tested, with three of them appearing to be
      highly sensitive: free proline, Hsp70, and malondialdehyde. Long-term follow-up
      analysis after metal exposure (27 days) also proves to be quite beneficial by
      providing a detailed overview of ecotoxicological events that is more complete
      and extensive than data recordings conducted over a few days. Taken together,
      these results support our initial hypothesis that leads to recommending biomarker
      analyses over at least 2 weeks of metal exposure.

PMID- 30229278
TI  - Geochemistry of Potentially Toxic Trace Elements in Soils of Mining Area: A Case
      Study from Zangezur Copper and Molybdenum Combine, Armenia.
AB  - Research was carried out to determine and asses the influence of mining
      industries on soil contamination with application of various pollution indices.
      For soil sampling 13 points were selected. Soil samples were analyzed for heavy
      metals by AAS. Eleven elements were determined and the greater quantities were
      generally observed in case of Mo and Cu. During the testing of soil pollution
      level pollution load index, degree of contamination (Cd) and geoaccumulation
      index were used. The correlation analysis revealed the strongest positive
      correlation between molybdenum and copper and that the high content of mentioned
      elements in soil was caused by mining industry. Assessment based on Cd showed
      that the 33.3% of A horizon soil samples referred to a very high degree of
      pollution. Obtained results will be useful for implementation of control measures
      of pollution and the remediation techniques.

PMID- 30229276
TI  - Effects of Glyphosate-, Glufosinate- and Flazasulfuron-Based Herbicides on Soil
      Microorganisms in a Vineyard.
AB  - In a vineyard we examined the effects of broad-spectrum herbicides with three
      different active ingredients (glyphosate, glufosinate, flazasulfuron) on soil
      microorganisms. Mechanical weeding served as control treatment. Treatments were
      applied within grapevine rows and soil samples taken from there in 10-20 cm depth
      77 days after application. Fungi were analyzed using classical sequencing
      technology and bacteria using next-generation sequencing. The number of colony
      forming units (CFU) comprising bacteria, yeasts and molds was higher under
      flazasulfuron compared to all other treatments which had similar CFU levels.
      Abundance of the fungus Mucor was higher under flazasulfuron than glufosinate and
      mechanical weeding; Mucor was absent under glyphosate. Several other fungi taxa
      were exclusively found under a specific treatment. Up to 160 different bacteria
      species were found - some of them for the first time in vineyard soils. Total
      bacterial counts under herbicides were on average 260% higher than under
      mechanical weeding; however due to high variability this was not statistically
      significant. We suggest that herbicide-induced alterations of soil microorganisms
      could have knock-on effects on other parts of the grapevine system.

PMID- 30229279
TI  - [Painful lymphadenopathy after an insect bite-a case report].
AB  - Tularemia is a bacterial zoonosis which is commonly transmitted through tick or
      insect bites or contact with meat of infected animals. We report the case of a 36
      year-old man who developed fever, chills, headaches, and a painful, unilateral,
      inguinal lymphadenopathy with a red-livid skin discoloration after an insect bite
      on his abdomen. Ulceroglandular tularemia was diagnosed through polymerase chain
      reaction (PCR) and serology. Treatment with doxycycline for 21 days resulted in
      an excellent outcome.

PMID- 30229281
TI  - [Regulator proteins of actin dynamics as possible targets of antineoplastic
      therapies].
AB  - BACKGROUND: The ability of tumor cells to leave the primary tumor is prerequisite
      for metastatic spread. In previous studies, we identified regulator proteins of
      actin reorganization with essential functions in both synaptogenesis and tumor
      cell migration. OBJECTIVE: The aim of the studies summarized in this article is
      to identify signaling pathways associated with actin-related proteins that might
      represent potential molecular targets for antiinvasive and/or antineoplastic
      therapies. MATERIALS AND METHODS: We used immunohistochemical analyses of protein
      expression as well as in vitro techniques (cell culture, fluorescence microscopy,
      RNAi-based knockdown of protein expression, protein biochemistry and in vivo
      animal experiment substitutes). RESULTS: We show that phosphorylation of Abelson
      interactor 1 (Abi1) is essential for the adhesion and invasion of colorectal
      carcinoma cells and might be targeted by the tyrosine kinase inhibitor
      STI571/Glivec(r). HnRNP K, a protein interaction partner of Abi1, is upregulated
      in malignant melanoma in response to ionizing radiation; this upregulation is
      impaired upon application of the MEK inhibitor PD98059, enhancing radiosensivity
      of melanoma. Edelfosin, an alkyl-lipid blocker of the Abi1 interaction partner
      SK3, inhibits invasion of urothelial carcinoma cells. CONCLUSION: The studies
      summarized in this overview confirm a central role for the investigated proteins
      in tumor cell invasion and resistance to antineoplastic therapies and identify
      possible molecular targets for novel therapeutic compounds.

PMID- 30229282
TI  - [Jurgen Vogel : 6 May 1946-23 July 2017].

PMID- 30229280
TI  - Infliximab biosimilar CT-P13 therapy in patients with Takayasu arteritis with low
      dose of glucocorticoids: a prospective single-arm study.
AB  - To evaluate the efficacy and safety of infliximab biosimilar CT-P13 in patients
      with active Takayasu arteritis (TAK). In this single-center open-label trial,
      patients with active TAK received CT-P13 at a starting dose of 5 mg/kg at weeks
      0, 2, 6, and then every 8 weeks up to week 46. They were followed up until week
      54. From week 14 to week 46, patients with inadequate response received increased
      dose of CT-P13 by 1.5 mg/kg. Concomitant prednisolone was allowed <= 10 mg/day.
      The primary efficacy end point was the achievement of partial or complete
      remission at week 30. All patients underwent positron emission tomography
      computed tomography (PET-CT) at baseline and week 30. Twelve patients with TAK
      received CT-P13; one patient with protocol violation was excluded from analysis.
      Nine (81.8%) patients had taken concomitant prednisolone with median dose of 5.0
      mg/day. At week 30, three (27.3%) patients achieved complete remission and six
      (54.5%) patients achieved partial remission. Statistically significant
      improvements in modified Indian Takayasu Clinical Activity Score (ITAS2010), ITAS
      A, and serum levels of erythrocyte sedimentation rate and C-reactive protein were
      seen at week 30 from baseline. PET parameters were significantly reduced from
      baseline to week 30, including maximum standardized uptake value, target-to-vein
      ratio, target-to-liver ratio, and PET Vascular Activity Score. There were no
      serious adverse events. Treatment with CT-P13 may lead to improvement in
      clinical, radiographic, and serological activities with lower glucocorticoid
      requirement in TAK.Trial registration number NCT02457585.

PMID- 30229283
TI  - [Crohn's disease-associated colorectal carcinogenesis : TP53 mutations and copy
      number gains of chromosome arm 5p as (early) markers of tumor progression].
AB  - BACKGROUND: Patients with inflammatory bowel diseases, i. e., ulcerative colitis
      and Crohn's disease (CD), face an increased risk of developing colorectal cancer
      (CRC). Evidence, mainly from ulcerative colitis, suggests that TP53 mutations
      represent an initial step in the progression from inflamed colonic epithelium to
      CRC. OBJECTIVES: In this study, we aimed to analyze the genetic events that
      define CD-CRCs, in particular the dynamics of their development from
      histologically undetectable precursor lesions to invasive disease. MATERIALS AND
      METHODS: We analyzed 73 tissue samples from 28 patients with CD-CRC, including
      precursor lesions by next generation sequencing (563 gene panel) and array-based
      comparative genomic hybridization. The results were compared with our own data
      and the Cancer Genome Atlas data on sporadic CRC. RESULTS: The gain of 5p was
      significantly more prevalent in CD-CRCs than in sporadic CRCs, despite an overall
      similar chromosomal aberration pattern. CD-CRCs had a distinct mutation signature
      with TP53 being the most frequently mutated gene in CD-CRCs. TP53 mutations and
      copy number alterations were early events in CD progression and could sometimes
      already be detected in non-dysplastic colonic mucosa, indicating occult tumor
      evolution. CONCLUSIONS: Molecular profiling of CD-CRCs and precursor lesions
      revealed an inflammation-associated landscape of genome alterations: gains of 5p
      and TP53 mutations occurred early in tumor development. Detection of these
      aberrations in precursor lesions may help predict disease progression and
      distinguishes CD-associated from sporadic colorectal neoplasia.

PMID- 30229284
TI  - [Minutes of the meeting of the working group on bone, joint, and soft tissue
      pathology : DGP Congress on 24 May 2018, Berlin].

PMID- 30229285
TI  - [Muraine sutures accelerate healing of corneal hydrops in acute keratotorus].
AB  - We report on a 52-year-old male patient presenting with unilateral loss of vision
      of one week's duration. Pellucid marginal corneal degeneration was known. Slit
      lamp examination showed pronounced corneal edema as defined by acute corneal
      hydrops. After inferior preventive YAG iridotomy through clear cornea,
      intracameral air injection was performed. Deep stromal 10-0 nylon sutures were
      applied along the Descemet's membrane tear. The next day, the corneal edema had
      already begun to decrease.

PMID- 30229286
TI  - [New/old viruses-up to the minute at any time].

PMID- 30229287
TI  - Overexpression of SmbHLH148 induced biosynthesis of tanshinones as well as
      phenolic acids in Salvia miltiorrhiza hairy roots.
AB  - KEY MESSAGE: SmbHLH148 activated the whole biosynthetic pathways of phenolic
      acids and tanshinones, thus upregulated the production of both the two groups of
      pharmaceutical ingredients in Salvia miltiorrhiza. Phenolic acids and tanshinones
      are the two important groups of pharmaceutical ingredients presented in Salvia
      miltiorrhiza Bunge. The bHLH transcription factors could regulate secondary
      metabolism efficiently in plants. However, there are only some MYCs have been
      studied on regulation of either phenolic acids or tanshinones biosynthesis. In
      this study, a bHLH TF named SmbHLH148, which is homologous to AtbHLH148,
      AtbHLH147 and CubHLH1, was isolated and functionally characterized from S.
      miltiorrhiza. Transcription of SmbHLH148 could be intensely induced by ABA and
      also be moderately induced by MeJA and GA. SmbHLH148 is present in all the six
      tissues and mostly expressed in fibrous root and flowers. Subcellular
      localization analysis found that SmbHLH148 was localized in the nucleus.
      Overexpression of SmbHLH148 significantly increased not only three phenolic acids
      components accumulation but also three tanshinones content. Content of caffeic
      acid, rosmarinic acid and salvianolic acid B were reached to 2.87-, 4.00- and
      5.99-fold of the control in the ObHLH148-3, respectively. Content of
      dihydrotanshinone I, cryptotanshinone, and tanshinone I were also present highest
      in ObHLH148-3, reached 2.5-, 5.04- and 3.97-fold of the control, respectively.
      Expression analysis of pathway genes of phenolic acids and tanshinones in
      transgenic lines showed that most of them were obviously upregulated. Moreover,
      transcription of AREB and JAZs were also induced in SmbHLH148 overexpression
      lines. These results suggested that SmbHLH148 might be taken part in ABA and MeJA
      signaling and activated almost the whole biosynthetic pathways of phenolic acids
      and tanshinones, thus the production of phenolic acids and tanshinones were
      upregulated.

PMID- 30229289
TI  - beta-Adrenergic signaling blocks murine CD8+ T-cell metabolic reprogramming
      during activation: a mechanism for immunosuppression by adrenergic stress.
AB  - Primary and secondary lymphoid organs are heavily innervated by the autonomic
      nervous system. Norepinephrine, the primary neurotransmitter secreted by post
      ganglionic sympathetic neurons, binds to and activates beta-adrenergic receptors
      expressed on the surface of immune cells and regulates the functions of these
      cells. While it is known that both activated and memory CD8+ T-cells primarily
      express the beta2-adrenergic receptor (beta2-AR) and that signaling through this
      receptor can inhibit CD8+ T-cell effector function, the mechanism(s) underlying
      this suppression is not understood. Under normal activation conditions, T-cells
      increase glucose uptake and undergo metabolic reprogramming. In this study, we
      show that treatment of murine CD8+ T-cells with the pan beta-AR agonist
      isoproterenol (ISO) was associated with a reduced expression of glucose
      transporter 1 following activation, as well as decreased glucose uptake and
      glycolysis compared to CD8+ T-cells activated in the absence of ISO. The effect
      of ISO was specifically dependent upon beta2-AR, since it was not seen in adrb2-/
      CD8+ T-cells and was blocked by the beta-AR antagonist propranolol. In addition,
      we found that mitochondrial function in CD8+ T-cells was also impaired by beta2
      AR signaling. This study demonstrates that one mechanism by which beta2-AR
      signaling can inhibit CD8+ T-cell activation is by suppressing the required
      metabolic reprogramming events which accompany activation of these immune cells
      and thus reveals a new mechanism by which adrenergic stress can suppress the
      effector activity of immune cells.

PMID- 30229288
TI  - Lysophosphatidylcholine induces cyclooxygenase-2-dependent IL-6 expression in
      human cardiac fibroblasts.
AB  - Lysophosphatidylcholine (LysoPC) has been shown to induce the expression of
      inflammatory proteins, including cyclooxygenase-2 (COX-2) and interleukin-6 (IL
      6), associated with cardiac fibrosis. Here, we demonstrated that LysoPC-induced
      COX-2 and IL-6 expression was inhibited by silencing NADPH oxidase 1, 2, 4, 5;
      p65; and FoxO1 in human cardiac fibroblasts (HCFs). LysoPC-induced IL-6
      expression was attenuated by a COX-2 inhibitor. LysoPC-induced responses were
      mediated via the NADPH oxidase-derived reactive oxygen species-dependent JNK1/2
      phosphorylation pathway, leading to NF-kappaB and FoxO1 activation. In addition,
      we demonstrated that both FoxO1 and p65 regulated COX-2 promoter activity
      stimulated by LysoPC. Overexpression of wild-type FoxO1 and S256D FoxO1 enhanced
      COX-2 promoter activity and protein expression in HCFs. These results were
      confirmed by ex vivo studies, where LysoPC-induced COX-2 and IL-6 expression was
      attenuated by the inhibitors of NADPH oxidase, NF-kappaB, and FoxO1. Our findings
      demonstrate that LysoPC-induced COX-2 expression is mediated via NADPH oxidase
      derived reactive oxygen species generation linked to the JNK1/2-dependent pathway
      leading to FoxO1 and NF-kappaB activation in HCFs. LysoPC-induced COX-2-dependent
      IL-6 expression provided novel insights into the therapeutic targets of the
      cardiac fibrotic responses.

PMID- 30229290
TI  - Orthopaedic publications from Egypt in the last five years: a bibliometric
      report.
AB  - INTRODUCTION: This review was done to find the trend for orthopaedic publications
      from Egypt in the last 5 years, detailing the specialties that are most published
      and comparing this with the surrounding Middle East region. METHODS: The search
      included orthopaedic-related articles published in journals that are listed in
      PubMed, including author affiliation from Egypt between 2013 and 2017. RESULTS:
      Four hundred eighty-one publications were found. The results showed that Trauma
      was the highest published branch while Arthroscopy has shown the highest increase
      since 2013 to become as Trauma by 2017. Two hundred seventy-two articles were
      published in Q1 and Q2 journals which represents 56.54% from the total
      publications. There were 1243 citations for these publications. The country
      ranking was between the fourth and fifth in Middle East region over the last five
      years. DISCUSSION: Publications are an important part of each country's research
      work. The trend for orthopaedic publication is showing an increase in
      subspecialty publications with a gradual increase in number of publications per
      year, while Egypt's position remains in the top five in the region.

PMID- 30229291
TI  - STEM tomography of high-pressure frozen and freeze-substituted cells: a
      comparison of image stacks obtained at 200 kV or 300 kV.
AB  - Scanning transmission electron microscopic (STEM) tomography of high-pressure
      frozen, freeze-substituted semi-thin sections is one of multiple approaches for
      three-dimensional recording and visualization of electron microscopic samples.
      Compared to regular TEM tomography thicker sample sections can be investigated
      since chromatic aberration due to inelastic scattering is not a limit. The method
      is ideal to investigate subcellular compartments or organelles such as synapses,
      mitochondria, or microtubule arrangements. STEM tomography fills the gap between
      single-particle electron cryo-tomography, and methods that allow investigations
      of large volumes, such as serial block-face SEM and FIB-SEM. In this article, we
      discuss technical challenges of the approach and show some applications in cell
      biology. It is ideal to use a 300-kV electron microscope with a very small
      convergence angle of the primary beam ("parallel" beam). These instruments are
      expensive and tomography is rather time consuming, and therefore, access to such
      a high-end microscope might be difficult. In this article, we demonstrate
      examples of successful STEM tomography in biology using a more standard 200-kV
      microscope equipped with a field emission tip.

PMID- 30229292
TI  - An efficient method for multigene co-interference by recombinant Bombyx mori
      nucleopolyhedrovirus.
AB  - Bombyx mori Nucleopolyhedrovirus (BmNPV), which is a member of the Baculoviridae
      family, is a significant pathogen of the silkworm. The infection of BmNPV is
      often lethal and causes about 20% loss of cocoon in the silk industry annually.
      To explore the effects of different gene inhibition strategies on the replication
      cycle of baculovirus, we constructed the mutant virus to infect BmN cells
      directly and further identified ie0, ie1, and gp64 as the essential viral genes
      of BmNPV. To elucidate the significance of the inhibition effect of different
      interference strategies, we characterized and constructed the recombinant BmNPV
      that carried a single or multigene-interfering cassette. The results showed that
      the inhibition effect of dsie1 on target gene expression, virus titer, and
      silkworm mortality was significantly better than that of dsie0 and dsgp64. It
      also showed that the dsie1 interference produced fewer progeny virions and was
      less lethal, which indicates that ie1 played a more critical role in the BmNPV
      replication cycle. Furthermore, the inhibitory effect of the virus titer and
      mortality indicated that the multigene co-interference constructed by the
      baculovirus expression system was significantly better than the interference of
      any single-gene (p < 0.05). In summary, the strategy of multigene synergy can
      achieve the function of continuous interference and provide a new platform for
      the breeding of silkworm disease resistant. In addition, this strategy improves
      the various traits of the silkworm.

PMID- 30229293
TI  - The influence of paternal diet on sncRNA-mediated epigenetic inheritance.
AB  - The risk of developing metabolic diseases is conferred by genetic predisposition
      from risk genes and by environmental exposures that can manifest in epigenetic
      changes. The global rise in obesity and type II diabetes has motivated a search
      for the epigenetic factors underlying these diseases. The possibility of
      transgenerational inheritance of epigenetic changes raises questions regarding
      how spermatozoa transmit acquired epigenetic changes that affect the metabolic
      health of the next generation. The purpose of this review is to describe current
      key literature concerning small non-coding RNA (sncRNA), specifically (1) the
      effects of high-fat or low-protein diets on sncRNA presence in spermatozoa; (2)
      sncRNA transmission from father to offspring; and (3) the functional effects of
      inherited sncRNA on offspring metabolic phenotype. Current research has
      identified alterations in the content of sncRNA subtypes, including microRNA
      (miRNA), Piwi-interacting RNA (piRNA), and transferRNA (tRNA)-derived small non
      coding RNA (tsncRNA), in spermatozoa in response to both high-fat diets and low
      protein diets. The altered content of spermatozoa sncRNA due to high-fat diets
      was associated with a changed phenotype in offspring, with offspring displaying
      insulin resistance, altered body weight, and glucose intolerance. The altered
      sncRNA content of spermatozoa due to a low-protein diet was associated with
      altered levels of lipid metabolites in offspring and decreased expression of
      specific genes starting in two-cell embryos. The current literature suggests that
      sncRNAs mediate paternal intergenerational epigenetic inheritance and thus has a
      direct functional importance, as well as possess biomarker potential, for
      metabolic diseases. Further research is urgently required to identify the
      specific sncRNAs with the most profound impacts.

PMID- 30229294
TI  - Coccidiostatic effects of tannin-rich diets in rabbit production.
AB  - The potential anti-eimerial effect of tannin containing resources such as
      sainfoin and carob in rabbits was tested on does at pre-weaning and to growing
      rabbits in their feed. The trial began at parturition (D0), when 24 does and
      their litters were assigned into three groups. They were fed either with a
      control (Group CO), a carob (containing 10% carob pods meal) (Group CP) or a
      sainfoin diet (containing 34% dehydrated sainfoin pellets) (Group SA). All diets
      were made isoproteic and isoenergetic and also balanced for crude fibre but
      differed by their tannin content. Weaning occurred at D37, and growing rabbits
      remained in the same cage until D51. Then, they were transferred to fattening
      cages until the end of the trial (D104) and slaughtering. Weight gain of young
      rabbits among the three groups (mean = 31.2 g/day) did not differ statistically.
      The mortality rates were 10% (SA), 15% (CP) and 20% (CO), respectively, but the
      differences were not statistically significant. Post-weaning economical feed
      conversion ratio (FCR) was reduced between rabbits of group SA compared to CO and
      CP groups. Faecal oocyst count (FOC) in group SA was 60% lower than in CO and CP
      groups. Areas under the curve (AUCs) calculated between sampling days and FOC,
      after transfer to fattening cages, was 62% lower in group SA than in CO and CP
      groups. The main Eimeria species identified (from D59 to D83) was Eimeria magna
      (53% of oocysts). AUCs for E. magna did not differ according to diet. In
      conclusion, the diet containing sainfoin reduced oocyst excretion of Eimeria spp.
      by 60%, and improved the economical FCR.

PMID- 30229295
TI  - Morphological and genetic characterisation of Sarcocystis halieti from the great
      cormorant (Phalacrocorax carbo).
AB  - Having examined 19 great cormorants (Phalacrocorax carbo) hunted in Lithuania,
      sarcocysts were found in the muscles of two birds. Sarcocysts detected were
      examined using light microscopy (LM), transmission electron microscopy (TEM), and
      18S rDNA, 28S rDNA, ITS1, cox1, and rpoB sequence comparison. Based on the
      molecular analysis, mainly of the ITS1 region, sarcocysts were identified as
      Sarcocystis halieti. This is the first Sarcocystis species characterised in the
      great cormorant. Under the LM sarcocysts were ribbon-shaped, very long and thin
      (the largest fragment found amounted to 6.5 * 0.1 mm) with a smooth and thin (up
      to 1.2 MUm) cyst wall. Banana-shaped bradyzoites were 7.2 * 1.9 (6.3-8.2 * 1.4
      2.4) MUm. Under TEM, the cyst wall was wavy, 0.8- to 1.2-MUm thick. The
      comparison of 12 species demonstrated cox1 and rpoB to be unsuitable for the
      identification of Sarcocystis spp. using birds as intermediate hosts.

PMID- 30229296
TI  - Influence of metrical structure on learning of positional regularities in
      movement sequences.
AB  - Sequential stimuli are usually perceived to have hierarchical temporal
      structures. However, some of these structures are only investigated in one type
      of sequence, regardless of the existing evidence, showing the domain-generality
      of the representation of these structures. Here, we assess whether the
      hierarchical representation of regularly segmented action sequences resembles the
      perceived metrical patterns that organize the representation of events
      hierarchically in temporally regular sequences. In all our experiments, we
      presented the participants with sequences of human movements and tested the
      perception of metrical pattern by segmenting the movement streams into temporally
      equal groups containing four movements. In Experiment 1, we found that a movement
      sequence with temporally equal groupings improves the learning of positional
      regularities inherent within each group of movements. To further clarify the
      degree to which this learning mechanism is affected by the perceived metrical
      patterns, we conducted Experiments 2a and 2b, in which the relative saliencies of
      the first and last positions in the movement groups, respectively, were studied.
      The results showed that, although in the learning of positional regularities, the
      rule-conforming first positions are as effective as when both first and last
      positions are legal, the last positions are not as influential. Based on these
      findings we conclude that, in grouped sequences, learning of positional
      regularities may be modulated by the metrical saliency patterns that are imposed
      by the temporal regularity of the sequential grouping pattern.

PMID- 30229297
TI  - To flourish or perish: evolutionary TRiPs into the sensory biology of plant
      herbivore interactions.
AB  - The interactions between plants and their herbivores are highly complex systems
      generating on one side an extraordinary diversity of plant protection mechanisms
      and on the other side sophisticated consumer feeding strategies. Herbivores have
      evolved complex, integrative sensory systems that allow them to distinguish
      between food sources having mere bad flavors from the actually toxic ones. These
      systems are based on the senses of taste, olfaction and somatosensation in the
      oral and nasal cavities, and on post-ingestive chemosensory mechanisms. The
      potential ability of plant defensive chemical traits to induce tissue damage in
      foragers is mainly encoded in the latter through chemesthetic sensations such as
      burning, pain, itch, irritation, tingling, and numbness, all of which induce
      innate aversive behavioral responses. Here, we discuss the involvement of
      transient receptor potential (TRP) channels in the chemosensory mechanisms that
      are at the core of complex and fascinating plant-herbivore ecological networks.
      We review how "sensory" TRPs are activated by a myriad of plant-derived
      compounds, leading to cation influx, membrane depolarization, and excitation of
      sensory nerve fibers of the oronasal cavities in mammals and bitter-sensing cells
      in insects. We also illustrate how TRP channel expression patterns and
      functionalities vary between species, leading to intriguing evolutionary
      adaptations to the specific habitats and life cycles of individual organisms.

PMID- 30229298
TI  - Hemodynamic effects of intramyometrial epinephrine injection for blood loss
      reduction in laparoscopic myomectomy.
AB  - PURPOSE: To evaluate changes in hemodynamic effects of intramyometrial
      epinephrine injection for blood loss reduction in laparoscopic myomectomy.
      METHODS: A total of 185 women with symptomatic uterine fibroids who underwent
      laparoscopic myomectomy were enrolled in this study. Eighty-six women (study
      collective) received an intramyometrial injection of epinephrine and were
      compared to ninety-nine women (control collective) who underwent laparoscopic
      myomectomy without an intramyometrial epinephrine injection. Demographic
      parameters, change of hemodynamic parameters during surgery as well as hemoglobin
      drop after surgery were analyzed. RESULTS: In the study collective maximum
      systolic blood pressure (p < 0.001), maximum increase of the systolic blood
      pressure within 5 min (p = 0.003), duration of hypertension (p = 0.012), maximal
      (p < 0.001) and mean heart rate (p = 0.005), maximal increase of heart rate
      within 5 min (p = 0.003) and difference of mean to maximal heart rate (p < 0.001)
      were higher compared to the control collective. There was no difference in pre-
      and postoperative hemoglobin levels in both collectives and no intraoperative
      clinically relevant complication occurred due to intramyometrial epinephrine
      injection. CONCLUSION: The intramyometrial application of epinephrine seems to be
      safe but leads to significant alterations of hemodynamic parameters without a
      significant change in postoperative hemoglobin levels.

PMID- 30229299
TI  - Development of the P300 from childhood to adulthood: a multimodal EEG and MRI
      study.
AB  - Maturation of attentional processes is central to cognitive development. The
      electrophysiological P300 is associated with rapid allocation of attention, and
      bridges stimulus and response processing. P300 is among the most studied and
      robust electrophysiological components, but how different subcomponents of the
      P300 develop from childhood to adulthood and relate to structural properties of
      the cerebral cortex is not well understood. We investigated age-related
      differences in both early visual and P300 components, and how individual
      differences in these components are related to cortical structure in a cross
      sectional sample of participants 8-19 years (n = 86). Participants completed a
      three-stimulus visual oddball task while high-density EEG was recorded. Cortical
      surface area and thickness were estimated from T1-weighted MRI. Group-level blind
      source separation of the EEG data identified two P300-like components, a fronto
      central P300 and a parietal P300, as well as a component reflecting N1 and P2.
      Differences in activity across age were found for the parietal P300, N1 and P2,
      with the parietal P300 showing stronger activity for older participants, while N1
      and P2 were stronger for younger participants. Stronger P300 components were
      positively associated with task performance, independently of age, while negative
      associations were found for P2 strength. Parietal P300 strength was age
      independently associated with larger surface area in a region in left lateral
      inferior temporal cortex. We suggest that the age differences in component
      strength reflect development of attentional mechanisms, with increased brain
      responses to task-relevant stimuli representing an increasing ability to focus on
      relevant information and to respond accurately and efficiently.

PMID- 30229300
TI  - Reduced CD8+ T cells infiltration can be associated to a malignant transformation
      in potentially malignant oral epithelial lesions.
AB  - OBJECTIVE: The aim of this study was to evaluate the immunohistochemical
      expressions of PD1, CD4+, and CD8+ in premalignant lesions (OPML) that were
      transformed into oral squamous cell carcinoma OSCC (OPML-OSCC), in OSCC and also
      in premalignant lesions that were not transformed into OSCC (OPML-NOSSC).
      MATERIALS AND METHODS: Retrospective analyses were performed in order to verify
      the demographic characteristics of the patients. CD4, CD8, and PD1 IMH studies
      were carried out on OPML and OSCC samples from 11 patients with OPML-OSCC and
      OPML, together with samples from 14 patients with OPML-NOSCC. The differences
      between OPML-OSCC and OPML-NOSCC were analyzed. RESULTS: Non-homogenous
      leukoplakia, together with the related oral subsite, and the lack of an exposure
      to tobacco, were all associated with malignant transformations. There were no
      statistical differences in the PD1 expression and the CD4+ cells in OPML-OSCC and
      OPML-NOSCC. A significant increment in the CD8+ cells was noted in the OPML that
      evolved into carcinomas when compared with OPML-NOSCC (p = 0.05), whereas there
      were higher CD8+ cells levels in the carcinomas when compared with the OPML that
      evolved into carcinomas (p = 0.027). CONCLUSIONS: CD8+ cells infiltrate more in
      OPML-NOSCC than in OPML-OSCC. Carcinoma is more infiltrated by CD8+ cells than
      its associated OPML. CLINICAL RELEVANCE: Understanding immunological factors
      associated with malignant transformation of oral premalignant lesions can open a
      new way to treat this disease.

PMID- 30229301
TI  - Full genome sequence of a novel iflavirus from the leafhopper Psammotettix
      alienus.
AB  - A novel iflavirus was discovered in Psammotettix alienus by RNA sequencing. The
      virus genome has 10,826 nucleotides (nt) excluding the poly A tail, encodes a
      3187-amino-acid polyprotein, and is tentatively named "Psammotettix alienus
      iflavirus 1" (PaIV1). PaIV1 has a similar genomic structure, conserved motifs,
      and a close phylogenetic relationship to members of the genus Iflavirus, but it
      shows only 41.9-55.2% sequence identity in the full genome and 16.2-49% in the
      deduced polyprotein. Thus, we suggest that it is a new member of the genus
      Iflavirus, family Iflaviridae.

PMID- 30229302
TI  - Hepatitis E virus infection in Wuhan, Central China.
AB  - Hepatitis E virus (HEV) is an emergent virus of global importance. Previous
      studies of HEV infection in China mainly focused on the rural areas. This work
      aims to study the epidemiology of HEV in a large urban environment. With a
      registered population of 10 million, the dense city of Wuhan presents itself as a
      prime opportunity to better understand this emergent virus. The epidemiological
      data from 2011 to 2016 were analyzed. A cross-sectional study on the
      seroprevalence of anti-HEV IgG was conducted among the general population (age
      range 0-59) in 2013. Serum and fecal samples of hepatitis E patients were
      collected over a period of two years: serum samples were tested for anti-HEV IgM
      and IgG, and fecal samples were tested for HEV-RNA. The overall seroprevalence of
      anti-HEV IgG was 35% in Wuhan. Among 415 hepatitis E patients, 286 cases (68.9%)
      were positive for HEV-IgM, 108 cases (26%) were positive for HEV-IgG alone, and
      21 cases (5.1%) were negative for both IgM and IgG. Phylogenetic analysis showed
      that the detected genotype of HEV was genotype 4. Reported cases occurred
      sporadically throughout the year with the peak value appearing in the first
      quarter and a large proportion of male cases (2.1:1). The incidence increased
      with age for persons under 60 years, reaching its peak level after 60 years of
      age. Wuhan is endemic for HEV with its currently detected genotype being genotype
      4. It is estimated that 68.9% hepatitis E cases were due to primary infection
      between 2012 and 2013 in Wuhan.

PMID- 30229303
TI  - Characterisation of a newly detected bacteriophage infecting Bordetella
      bronchiseptica in swine.
AB  - A novel virulent bacteriophage, vB_BbrM_PHB04, infecting Bordetella
      bronchiseptica was isolated from wastewater collected at a swine farm in China.
      Phage vB_BbrM_PHB04 exhibited growth over a wide range of temperature and pH
      conditions and showed different efficiency of plating values and lytic spectra
      within the same strains at 25  degrees C and 37  degrees C. High-throughput
      sequencing revealed that vB_BbrM_PHB04 has a linear double-stranded DNA genome
      with 124 putative open reading frames. Overall, the genome of vB_BbrM_PHB04
      showed very low similarity (the highest nucleotide identity 82%, 1% coverage) to
      other phage sequences in the GenBank database. Phylogenetic analysis indicated
      that vB_BbrM_PHB04 is a new member of the family Myoviridae. In addition,
      polymerase chain reaction-based detection of phage genes in phage-resistant B.
      bronchiseptica variants revealed no evidence of lysogenic activity of phage
      vB_BbrM_PHB04.

PMID- 30229304
TI  - Retinal pigment epithelium hyperplasia overlying pigment epithelial detachment in
      age-related macular degeneration can masquerade as neovascularization on optical
      coherence tomography angiography.
AB  - PURPOSE: To report the image artifacts due to retinal pigment epithelium (RPE)
      hyperplasia overlying retinal pigment epithelial detachment (PED) in age-related
      macular degeneration (AMD), which can masquerade as neovascularization on optical
      coherence tomography angiography (OCTA). METHODS: A hospital-based,
      retrospective, and cross-sectional study. Twenty-two eyes from 16 patients with
      non-vascularized PED related to AMD were included in this study. All patients
      were examined by OCTA, spectral-domain optical coherence tomography, fluorescence
      angiography, and indocyanine green angiography. Vascular flow signals (VFS) on
      both the outer retinal slab of en face OCTA and cross-sectional OCTA and their
      correspondence with RPE hyperplasia were evaluated. RESULTS: Fifteen eyes (68.2%)
      showed VFS on both the outer retina slab of en face OCTA and cross-sectional
      OCTA, all corresponding to the RPE hyperplasia overlying PED. Among them, 12 eyes
      with lump RPE hyperplasia outside foveal avascular zone (FAZ) all showed obvious
      VFS on the outer retina slab of OCTA, and 3 eyes with scattered RPE hyperplasia
      outside FAZ showed VFS fragments. Of note, 4 eyes had accompanied RPE hyperplasia
      inside FAZ, and 7 eyes without RPE hyperplasia overlying PED showed no
      corresponding VFS on the outer retina slab of OCTA. Additionally, a round-like
      dark band at the edge of PED was observed in the outer retina slab on en face
      OCTA in 17 eyes (77.3%). CONCLUSIONS: RPE hyperplasia overlying PED in AMD can
      masquerade as neovascularization on OCTA. To avoid misdiagnosis and unnecessary
      treatment, this RPE hyperplasia-related image artifact should be considered when
      interpreting OCTA images.

PMID- 30229306
TI  - Barriers and facilitators to shared decision making in child and youth mental
      health: clinician perspectives using the Theoretical Domains Framework.
AB  - Shared decision making (SDM) is increasingly being suggested as an integral part
      of mental health provision. Yet, there is little research on what clinicians
      believe the barriers and facilitators around practice to be. At the same time,
      there is also increasing recognition of a theory-practice gap within the field,
      with calls for more pragmatic uses of theory to inform and improve clinical
      practice. Using the Theoretical Domains Framework (TDF), a comprehensive,
      theoretical-led framework, underpinned by 33 behaviour change theories and 128
      constructs, clinician perceived barriers and facilitators to SDM are
      investigated. The sample comprised of 15 clinicians across two sites in England,
      who took part in qualitative semi-structured interviews and focus groups.
      Transcripts were analysed using a deductive thematic analysis, and themes were
      coded under each theoretical domain. Overall, 21 barriers and facilitators for
      SDM in child and youth mental health were identified across ten domains of the
      TDF. Under capability, barriers and facilitators were found for knowledge,
      skills, memory/attention/decision making processes, and behavioural regulation.
      For opportunity, barriers and facilitators were found for social influences, as
      well as environmental context and resources. Finally, for motivation, domains
      covered included: beliefs about consequences, beliefs about capabilities,
      emotions, and professional role and identity. Findings suggest that a range of
      barriers and facilitators affect clinicians' abilities to engage in SDM with
      young people and parents. Interventions which target different domains related to
      capability, opportunity and motivation should be developed to better facilitate
      young people and their families in care and treatment decisions.

PMID- 30229305
TI  - Hear speech, change your reach: changes in the left-hand grasp-to-eat action
      during speech processing.
AB  - Research has shown that the kinematic characteristics of right-hand movements
      change when executed during both speech production and processing. Despite the
      variety of prehension and manual actions used to examine this relationship, the
      literature has yet to examine potential movement effects using an action with a
      distinct kinematic signature: the hand-to-mouth (grasp-to-eat) action. In this
      study, participants performed grasp-to-eat and grasp-to-place actions in (a) a
      quiet environment and (b) while processing speech. Results during the quiet
      condition replicated the previous findings; consistently smaller grasp-to-eat
      (compared to grasp-to-place), maximum grip apertures appeared only when using the
      right hand. Interestingly, in the listen condition, smaller maximum grip
      apertures in the grasp-to-eat movement appeared in both the right and left hands,
      despite the fact that participants were right-handed. This paper addresses these
      results in relation with similar behaviour observed in children, and discusses
      implications for functional lateralization and neural organization.

PMID- 30229307
TI  - Deficits in auditory sensory discrimination among children with attention
      deficit/hyperactivity disorder.
AB  - Research into children with attention-deficit/hyperactivity disorder (ADHD) has
      focused on complex cognitive dysfunction, but less attention has been paid to
      sensory perception processes underlying the symptoms of ADHD. Based on signal
      detection theory, the present study compared the sensory discrimination ability
      and decision bias of children with and without ADHD. It also investigated the
      differences between ADHD with predominantly inattentive (ADHDi) and combined
      presentations (ADHDc). The sample of 75 children and adolescents with ADHD (24
      ADHDi, 51 ADHDc) (16 females and 59 males) and 22 typical developing controls
      (TD) (8 females and 14 males) completed an auditory signal detection task.
      Participants were asked to detect signals against levels of transient background
      noise (35, 45, 55, and 65 dB). The results showed that with the increase of noise
      levels, both the ADHD and TD groups demonstrated decreased sensory
      discrimination. Although both groups successfully detected signal against noise
      levels from 35 to 55 dB, the ADHD group showed lower discrimination ability than
      that of the TD group. For decision bias, no group difference was found. Further
      comparisons regarding the predominant symptom presentation of ADHD sub-groups
      showed no differences. Current research has suggested that the deficit in ADHD
      people's signal detection performance can be attributed to sensory discrimination
      rather than decision bias. We suggest that background noise should be taken into
      account when using auditory stimuli to investigate cognitive functions in people
      with ADHD.

PMID- 30229308
TI  - Breast and complementary feeding in Ethiopia: new national evidence from
      systematic review and meta-analyses of studies in the past 10 years.
AB  - PURPOSE: The aim of this systematic review and meta-analysis was to provide a
      national estimate of breast and complementary feeding practices and its
      predictors in Ethiopia. METHODS: PubMed, SCOPUS, EMBASE, CINHAL, Web of Science
      and WHO Global Health Library electronic databases were searched for all
      available literature published until April 2018. Observational studies including
      cross-sectional, case-control and cohort studies were included. Newcastle-Ottawa
      Scale was used to assess the quality of studies. Heterogeneity of studies was
      quantified using Cochran's Q chi2 statistic and Higgins's method (I2). A meta
      analysis using a weighted inverse variance method was performed. Subgroup
      analysis was carried out based on region and study area. RESULTS: In total, 70
      studies that involved > 55,000 women from nine regions and two chartered cities
      in Ethiopia were included. The pooled national prevalence for timely initiation
      of breastfeeding (TIBF), exclusive breastfeeding (EBF) and timely initiation of
      complementary feeding was 66.5%, 60.1% and 62.5%, respectively. Guidance and
      counselling on breastfeeding, vaginal delivery and health institution delivery
      significantly increased the odds of TIBF and EBF. In addition, TIBF significantly
      associated with high EBF practice. Maternal occupational status significantly
      associated with low EBF practice, but not TIBF. CONCLUSIONS: Based on the WHO
      standard, the current breast and complementary feeding practice in Ethiopia is
      good and improving. Integrated intervention is still required for further
      improvement and minimizing the effect of occupational status.

PMID- 30229309
TI  - New approach for the determination of ortho-phenylphenol exposure by measurement
      of sulfate and glucuronide conjugates in urine using liquid chromatography-tandem
      mass spectrometry.
AB  - Ortho-phenylphenol (OPP) has been widely used as a fungicide and preservative.
      Although low-dose studies have demonstrated its low toxicity in animals and
      humans, high-dose exposure to this contaminant has toxic effects that range from
      skin irritation to bladder cancer. Thus far, monitoring of OPP exposure in the
      general population has been performed by measuring OPP after urine hydrolysis
      with the beta-glucuronidase/arylsulfatase enzyme and sometimes by the use of a
      mineral acid. We developed a sensitive, accurate, and robust method using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) to specifically measure two
      phase II OPP metabolites excreted in human urine, OPP sulfate (OPP-S), and OPP
      glucuronide (OPP-G). Comparative analysis of urine samples from 50 volunteers
      living in the Quebec City area using a direct method and phosphoric acid
      hydrolysis method previously developed in our laboratory showed no statistically
      significant difference (p value for paired t test = 0.701) in OPP concentrations.
      Moreover, a significant difference showed that underestimation (p value for
      paired t test = 0.025) occurs when beta-glucuronidase/arylsulfatase enzyme
      deconjugation is used. The LOD achieved by the direct method permits the
      detection of OPP-S and OPP-G metabolites in urine at the submicrogram per liter
      level. Graphical abstract ?.

PMID- 30229310
TI  - Ionic liquid matrices for MALDI mass spectrometry of lignin.
AB  - The use of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry
      for the study of lignin is still extremely limited due to its low ionization
      efficiency. We have developed an approach for obtaining high-intensity MALDI mass
      spectra of lignin, based on the use of ionic liquids as matrices. Thirty-two
      ionic liquids consisting of large nitrogen-containing cations and anions of
      aromatic acids, traditionally used as crystalline matrices, were tested. It was
      established that ionic liquids based on N,N-diisopropyl-N-ethylammonium, N
      isopropyl-N-methyl-N-tert-butylammonium, 3-aminoquinolinium, pyridinium, and 1
      methylimidazolium cations and anions of ferulic, alpha-cyanohydroxycinnamic, and
      2,5-dihydroxybenzoic acids as MALDI matrices provided high efficiency of lignin
      desorption/ionization with generation of singly charged protonated molecules of
      its oligomers. The use of such matrices in combination with the MALDI quadrupole
      ion trap-time-of-flight technique allows high-intensity mass spectra of lignin to
      be obtained without interferences from the matrix in the molecular weight range
      up to 3 kDa, adequately reflecting the molecular mass characteristics of lignin
      preparations. Using ionic liquid matrices, MS2 and MS3 MALDI mass spectra of
      lignins for various precursor ions were first obtained, including in the region
      of large (> 2 kDa) molecular weights. Differences in tandem mass spectra of
      coniferous and deciduous lignins, reflecting the structural features of
      corresponding oligomers were demonstrated. Graphical abstract ?.

PMID- 30229311
TI  - A single-nucleotide polymorphism in a gene modulating glucocorticoid sensitivity
      is associated with the decline in total lung capacity after lung transplantation.
AB  - PURPOSE: Glucocorticoids are used to prevent chronic lung allograft dysfunction
      (CLAD) after lung transplantation (LT). Our study was aimed at assessing the
      association between the glucocorticoid-induced transcript 1 gene (GLCCI1)
      variant, which modulates glucocorticoid sensitivity, and the postoperative lung
      function and development of CLAD after LT. METHODS: A total of 71 recipients of
      LT were genotyped for the GLCCI1 variant (rs37972) and divided into three groups:
      the homozygous mutant allele (TT) group, the heterozygous mutant allele (CT)
      group, and the wild-type allele (CC) group. The results of pulmonary function
      tests were compared with the postoperative baseline values. RESULTS: The total
      lung capacity (TLC) in the TT group was significantly lower than that in the CC
      group at 3 years after LT (P = 0.029). In the recipients of cadaveric LT, the TLC
      and forced expiratory volume in 1 s in the TT group were significantly lower than
      those in the CC groups, resulting in a significant worse CLAD-free survival at 3
      years after LT (P = 0.016). CONCLUSION: The GLCCI1 variant was associated with a
      significant decrease of the TLC at 3 years after LT and the development of CLAD
      at 3 years, especially in patients undergoing cadaveric LT.

PMID- 30229312
TI  - Correction to: Microtissue size and cell-cell communication modulate cell
      migration in arrayed 3D collagen gels.
AB  - The original version of this article unfortunately contained a mistake. One line
      indicating statistical significance was improperly placed in Fig. 5.

PMID- 30229314
TI  - Vegetarian Diets and the Risk of Diabetes.
AB  - PURPOSE OF REVIEW: Worldwide, diabetes has increased steadily and in recent
      years, drastically. The majority of diabetes cases are type 2 (T2DM), caused by
      modifiable risk factors such as diet. Vegetarian diets have been studied over the
      past few decades for their preventative and therapeutic effects on diabetes and
      may be more beneficial than medication for diabetes management. RECENT FINDINGS:
      A vegetarian diet characterized by whole plant foods is most beneficial for
      diabetes prevention and management. Vegetarian diets are inversely associated
      with risk of developing diabetes independent of the positive association of meat
      consumption with diabetes development. Vegetarian diets range from vegan (no
      animal products), lacto-ovo-vegetarian (no animal meat, but consumes milk and
      eggs), pesco-vegetarian (consumes fish), and semi-vegetarian (occasional meat
      consumption). There has been an observed difference in the extent of preventative
      and therapeutic effects of these different types of diets. The most important
      aspect of any of these types of diets is emphasizing whole grains, fruits and
      vegetables, legumes, and nuts and reducing saturated and trans fats.

PMID- 30229315
TI  - Research on the Realization of Remote Clinical Skills Training.
AB  - According to the analysis of investigation, there are many problems in the
      current clinical skills training for medical education, such as large demand,
      high difficulty and less opportunity. With the development and application of
      computer network technology, it has provided new directions for the training in
      the medical field. Using modern management techniques, it has combined computer
      technology, biochemical science and microbiology principles with traditional
      clinical medical education experience, which has promoted the development of
      advanced clinical medicine concepts and skill levels. The combination of distance
      education and medical education is a process of integrating theoretical knowledge
      into practice, which not only improve the medical management capabilities of
      medical staff, but also improve the overall level of clinical skills.

PMID- 30229313
TI  - Red Meat Consumption (Heme Iron Intake) and Risk for Diabetes and Comorbidities?
AB  - PURPOSE OF REVIEW: To examine the role of red meat consumption, especially heme
      iron intake, and risk for diabetes and its comorbidities. RECENT FINDINGS:
      Studies consistently show that consumption of red meat has been contributory to a
      multitude of chronic conditions such as diabetes, CVD, and malignancies. There
      are various emerging reasons that strengthen this link-from the basic
      constituents of red meat like the heme iron component, the metabolic reactions
      that take place after consumption, and finally to the methods used to cook it.
      The causative links show that even occasional use raises the risk of T2DM. Prior
      studies show how nitrites and nitrates in red meat can lead to increased insulin
      resistance, dysregulated blood glucose levels, and elevated oxidative stress all
      leading to chronic diseases. With the rise in these preventable chronic diseases,
      we examine how disease-causing links can be eliminated with appropriate lifestyle
      choices.

PMID- 30229316
TI  - Solvothermal synthesis of phosphorus and nitrogen doped carbon quantum dots as a
      fluorescent probe for iron(III).
AB  - Carbon quantum dots (CQDs) doped with phosphorus and nitrogen were prepared via a
      hydrothermal method starting from citric acid, urea and phosphoric acid in
      dimethylformamide solution. The size, morphology, surface composition, energy
      levels, and optical properties of the CQDs were characterized. They show both
      green down-conversion and up-conversion fluorescence. Ferric ions (Fe3+) are
      found to quench the fluorescence. Cyclic voltammetry was used to identify the
      HOMO and LUMO levels of the doped CQDs. The quenching mechanism, as confirmed by
      energy level calculations and absorption spectra, can be attributed to the
      selective coordination of Fe3+ by the surface functional groups on the CQDs. This
      facilitates the photo-induced electron transfer from the CQDs to the d orbitals
      of Fe3+. The CQDs are shown to be viable fluorescent probes for determination of
      Fe3+ with high selectivity and sensitivity. The assay has a linear response in
      the 0.1 MUM to 0.9 MUM Fe3+ concentration range and a 50 nM as limit of detection
      (at a S/N ratio of 3). Graphical abstract Fluorescence probe for determination of
      ferric ions based on carbon quantum dot quenching via chelation facilitate photo
      electron transfer.

PMID- 30229318
TI  - ?

PMID- 30229317
TI  - Prenatal Diet and the Development of Childhood Allergic Diseases: Food for
      Thought.
AB  - PURPOSE OF REVIEW: The development of allergic disease is shaped by genetics and
      the environment, including diet. Many studies suggest a role for maternal diet
      during pregnancy. In this article, we discuss potential mechanisms by which
      specific nutrients, particular foods, and dietary patterns may influence allergic
      disease development and review studies examining the relationship between
      prenatal diet and the risk of childhood allergy. RECENT FINDINGS: The combination
      of in utero exposures and genetic predisposition may contribute to the
      development of allergic disease by altering immune and organ development.
      Inflammation predominates in the first and third trimesters whereas the second
      trimester is characterized by anti-inflammatory and Th2 immune responses.
      Maternal dietary exposures during pregnancy may interact with inherited genetic
      risk factors influence immune system development. There are varied results
      regarding the impact of maternal prenatal diet on the development of childhood
      allergies. Well-designed randomized controlled studies are needed to clarify this
      area.

PMID- 30229319
TI  - Unique dynamic crossover in supercooled x,3-dihydroxypropyl acrylate (x = 1, 2)
      isomers mixture.
AB  - The previtreous dynamics in the glass-forming monomer, glycerol monoacrylate
      (GMA), was tested using the broadband dielectric spectroscopy (BDS). The
      measurements revealed a clear dynamic crossover at the temperature [Formula: see
      text] K and the time scale [Formula: see text] ns for the primary (structural)
      relaxation time and no hallmarks for the crossover for the DC electric
      conductivity [Formula: see text]. This result was revealed via the derivative
      based and distortions-sensitive analysis [Formula: see text] vs. [Formula: see
      text] , where [Formula: see text] stands for the apparent activation energy.
      Subsequent tests of the fractional Debye-Stokes-Einsten relation [Formula: see
      text] showed that the crossover is associated with [Formula: see text] [Formula:
      see text] (for [Formula: see text]. The crossover coexists with the emergence of
      the secondary beta relaxation, which smoothly develops deeply into the solid
      amorphous phase below the glass temperature [Formula: see text].

PMID- 30229321
TI  - Preaponeurotic endoscopic repair (REPA) of diastasis recti associated or not to
      midline hernias.
AB  - BACKGROUND: Diastasis recti is a common pathology during pregnancy and
      puerperium, usually associated with midline hernias, with aesthetic and
      symptomatic problems. This approach allows us to restore the alba line, without
      entering the abdominal cavity. MATERIALS AND METHODS: Between April 2014 and July
      2017, 50 patients underwent surgery, 94% female (mean age 38). Ultrasonography
      confirmed diagnosis. Recti diastasis was associated with midline defects in 100%.
      The preaponeurotic endoscopic repair is done with suprapubic approach and in both
      iliac fossae. A preaponeurotic new cavity was created with dissection of the
      subcutaneous cellular tissue and then recti plication with barbed suture was
      performed. The wall is reinforced with polypropylene mesh. Drainage is left
      systematically. RESULTS: Diastasis recti < 50 mm (55.5%) was diagnosed, from 51
      to 80 mm (29.6%), and > 81 mm (14.9%). Recti plication with bearded suture was
      performed. It was associated with external oblique release in 32% of patients,
      being unilateral (87.5%). Light/intermediate (90%) and heavy (10%) polypropylene
      meshes were placed, being fixed with absorbable (62%) and non-absorbable material
      (38%). Navel was reinserted using internal or external sutures. The average
      surgical time is 83 min. There are no intraoperative complications, but PO seroma
      finding 12%. The average hospital stay was 1.3 days, with pain level 3/10
      according to AVS. The patients returned to their usual activities after 16.5
      days. No complications or recurrences were observed by clinical and sonographic
      control at 18 months in 74% of patients. The patients were followed up at 39
      months. Patient satisfaction was reported as 96%. CONCLUSIONS: Diastasis recti is
      a common pathology with aesthetic and symptomatic problems. Endoscopic surgery
      allowed us to resolve the parietal defect with plication of recti and placement
      of preaponeurotic reinforcement prosthesis, increasing the safety of the repair,
      without entering the abdominal cavity, with a short hospitalization and no
      complications or recurrence in 3 years.

PMID- 30229320
TI  - Characterization of peroxo reaction intermediates in the water oxidation process
      on hematite surfaces.
AB  - We use density functional theory-based calculations to study structural,
      electronic, and magnetic properties of two key reaction intermediates on a
      hematite, [Formula: see text]-Fe2O3, photoanode during the solar-driven water
      splitting reaction. Both intermediates contain an oxygen atom bonded to a surface
      iron atom. In one case, the adsorbed oxygen also forms a peroxo bond with a
      lattice oxygen from hematite; in the second case no such bond is formed. Both
      configurations are energetically equivalent and are related to the overpotential
      determining step in the oxygen evolution reaction. The calculated reaction path
      for the breaking of the peroxo bond shows a barrier of about 0.86 eV for the
      transformation between the two intermediates. We explain this high barrier with
      the drastically different electronic and magnetic structure, which we also
      analyze using maximally localized Wannier functions. Photo-generated electron
      holes are shown to localize preferentially close to the reaction center at the
      surface in both configurations. In the case of the oxo species, this localization
      favors subsequent electron transfer steps during the oxygen evolution cycle. In
      the case of the peroxo configuration, this fact together with the high barrier
      for breaking the oxygen-oxygen bond indicates a possible loss mechanism due to
      hole trapping. Graphical Abstract Calculated spin density at a hematite surface
      with peroxo intermediate.

PMID- 30229322
TI  - ndpT encodes a new protein involved in nicotine catabolism by Sphingomonas
      melonis TY.
AB  - Sphingomonas melonis TY utilizes nicotine as a sole source of carbon, nitrogen,
      and energy to grow. One of the genes in its ndp catabolic cluster, ndpT, encodes
      a hypothetical transporter. Since no transporter for nicotine has been identified
      in microorganisms, we investigated whether NdpT is responsible for nicotine
      transport. ndpT was induced by nicotine, and gene knockout and complementation
      studies clearly indicated that ndpT is essential for the catabolism of nicotine
      in strain TY. NdpT-GFP was located at the periphery of the cells, suggesting that
      NdpT is a membrane protein. Uptake assays with L-[14C] nicotine illustrated that
      nicotine uptake in strain TY is mediated by a constitutively synthesized permease
      with a Km of 0.362 +/- 0.07 MUM and a Vmax of 0.762 +/- 0.068 MUmol min-1 (mg
      cell dry weight)-1 and that ndpT may play a role in nicotine exclusion. Hence, we
      consider NdpT a nicotine catabolism-related protein.

PMID- 30229323
TI  - Genome-wide screening identifies promiscuous phosphatases impairing terpenoid
      biosynthesis in Escherichia coli.
AB  - Terpenoids are a large family of natural compounds that are important for both
      biotechnological applications and basic microorganism physiology. Inspired by the
      current literature, we hypothesized that recently deciphered phosphatase
      promiscuity may be an unexplored factor that negatively affects terpenoid
      biosynthesis by redirecting carbon flux away from the pathway via unrecognized
      catalytic activities on the phosphorylated intermediates. We used lycopene as a
      proof-of-concept to test this hypothesis. Based on an extensive bioinformatics
      analysis, we selected 56 phosphatase-encoding genes in Escherichia coli and
      constructed a knockdown library for these genes in a lycopene overproducer via
      CRISPR interference (CRISPRi). We screened this phosphatase knockdown library and
      observed enrichment (28 of 56) for genes that impair lycopene biosynthesis.
      Further scaled-up cultivation, combinatorial knockdown, and knockout assays in
      strains that overproduce lycopene or another terpenoid (beta-carotene) confirmed
      the proposed relationship between promiscuous phosphatases and impaired terpenoid
      biosynthesis. This study hence suggests the necessity of reconsidering the
      interactions of promiscuous phosphatases with ubiquitous phosphorylated
      components of metabolic networks with respect to engineering metabolism.

PMID- 30229324
TI  - Structural and functional properties of antimicrobial protein L5 of Lysobacter
      sp. XL1.
AB  - The Gram-negative bacterium Lysobacter sp. XL1 secretes into the extracellular
      space five bacteriolytic enzymes that lyse the cell walls of competing
      microorganisms. Of special interest are homologous lytic proteases L1 and L5.
      This work found protein L5 to possess Gly-Gly endopeptidase and N-acetylmuramoyl
      L-Ala amidase activities with respect to staphylococcal peptidoglycan. Protein L5
      was found to be capable of aggregating into amyloid-like fibril structures. The
      crystal structure of protein L5 was determined at a 1.60-A resolution. Protein L5
      was shown to have a rather high structural identity with bacteriolytic protease
      L1 of Lysobacter sp. XL1 and alpha-lytic protease of Lysobacter enzymogenes at a
      rather low identity of their amino acid sequences. Still, the structure of
      protein L5 was revealed to have regions that differed from their equivalents in
      the homologs. The revealed structural distinctions in L5 are suggested to be of
      importance in exhibiting its unique properties.

PMID- 30229325
TI  - Enhanced synthesis of poly gamma glutamic acid by increasing the intracellular
      reactive oxygen species in the Bacillus licheniformis Delta1-pyrroline-5
      carboxylate dehydrogenase gene ycgN-deficient strain.
AB  - Poly gamma glutamic acid (gamma-PGA) is an anionic polyamide with numerous
      applications. Previous studies revealed that L-proline metabolism is implicated
      in a wide range of cellular processes by increasing intercellular reactive oxygen
      species (ROS) generation. However, the relationship between L-proline metabolism
      and gamma-PGA synthesis has not yet been analyzed. In this study, our results
      confirmed that deletion of Delta1-pyrroline-5-carboxylate dehydrogenase gene ycgN
      in Bacillus licheniformis WX-02 increased gamma-PGA yield to 13.91 g L-1, 85.22%
      higher than that of the wild type (7.51 g L-1). However, deletion of proline
      dehydrogenase gene ycgM had no effect on gamma-PGA synthesis. Furthermore, a 2.92
      fold higher P5C content (19.24 MUmol gDCW-1) was detected in the ycgN deficient
      strain WXDeltaycgN, while the P5C levels of WXDeltaycgM and the double mutant
      strain WXDeltaycgMN showed no difference, compared to WX-02. Moreover, the ROS
      level of WXDeltaycgN was increased by 1.18-fold, and addition of n-acetylcysteine
      (antioxidant) decreased its ROS level, which further reduced gamma-PGA synthesis
      capability of WXDeltaycgN. Collectively, our results demonstrated that proline
      catabolism played an important role in maintaining ROS homeostasis, and deletion
      of ycgN-enhanced P5C accumulation, which induced a transient ROS signal to
      promote gamma-PGA synthesis in B. licheniformis.

PMID- 30229326
TI  - Phase behaviour of colloidal superballs mixed with non-adsorbing polymers.
AB  - Inspired by experimental work on colloidal cuboid-polymer dispersions (Rossi et
      al., Soft Matter, 7, 4139 (2011)) we have theoretically studied the phase
      behaviour of such mixtures. To that end, free volume theory (FVT) was applied to
      predict the phase behaviour of mixtures of superballs and non-adsorbing polymer
      chains in a common solvent. Closed expressions for the thermodynamic properties
      of a suspension of hard colloidal superballs have been derived, accounting for
      fluid (F), face-centred cubic (FCC) and simple cubic (SC) phase states. Even
      though the considered solid phases are approximate, the hard superballs phase
      diagram semi-quantitatively matches with more evolved methods. The theory
      developed for the cuboid-polymer mixture reveals a rich phase behaviour, which
      includes not only isostructural F1-F2 coexistence, but also SC1-SC2 coexistence,
      several triple coexistences, and even a quadruple-phase coexistence region (F1-F2
      SC-FCC). The model proposed offers a tool to asses the stability of cuboid
      polymer mixtures in terms of the colloid-to-polymer size ratio.

PMID- 30229327
TI  - Microbial calcium carbonate precipitation with high affinity to fill the concrete
      pore space: nanobiotechnological approach.
AB  - Despite the advantages of concrete, it has a pore structure and is susceptible to
      cracking. The initiated cracks as well as pores and their connectivity accelerate
      the structure degradation by permitting aggressive substances to flow into the
      concrete matrix. This phenomenon results in a considerable repair and maintenance
      costs and decreases the concrete lifespan. In recent years, biotechnological
      approach through immobilization of bacteria in/or protective vehicles has emerged
      as a viable solution to address this issue. However, the addition of macro- or
      micro scale size particles can decrease the integrity of matrix. In this study,
      the immobilization of bacteria with magnetic iron oxide nanoparticle (ION) was
      proposed to protect the bacterial cell and evaluate their effect on healing the
      concrete pore space. The results show that the addition of immobilized bacteria
      with IONs resulted in a lower water absorption and volume of permeable pore
      space. Crystal analysis using scanning electron microscope (SEM) and energy
      dispersive X-ray spectroscopy (EDS) revealed that CaCO3 was precipitated in bio
      concrete specimen as a result of microbial biosynthesis.

PMID- 30229328
TI  - Application of high-voltage electrical discharges and high-pressure
      homogenization for recovery of intracellular compounds from microalgae
      Parachlorella kessleri.
AB  - Treatments with high-voltage electrical discharges (HVED) and high-pressure
      homogenization (HPH) were studied and compared for the release of ionic
      components, carbohydrates, proteins, and pigments from microalgae Parachlorella
      kessleri (P. kessleri). Suspensions (1% w/w) of microalgae were treated by HVED
      (40 kV/cm, 1-8 ms) or by HPH (400-1200 bar, 1-10 passes). Particle-size
      distribution (PSD) and microscopic analyses were used to detect the disruption
      and damage of cells. HVED were very effective for the extraction of ionic cell
      components and carbohydrates (421 mg/L after 8 ms of the treatment). However,
      HVED were ineffective for pigments and protein extraction. The concentration of
      proteins extracted by HVED was just 750 mg/L and did not exceed 15% of the total
      quantity of proteins. HPH permitted an effective release overall of intracellular
      compounds from P. kessleri microalgae including a large quantity of proteins,
      whose release (at 1200 bar) was 4.9 times higher than that obtained by HVED.
      Consequently, HVED can be used at the first step of the overall extraction
      process for the selective recovery of low-molecular-weight components. HPH can be
      then used at the second step for the recovery of remaining cell compounds.

PMID- 30229329
TI  - Intraoperative ultrasonic navigation for laparoscopic colorectal surgery with
      preservation of the left colic artery.

PMID- 30229330
TI  - Carbon nanotubes and crystalline silica induce matrix remodeling and contraction
      by stimulating myofibroblast transformation in a three-dimensional culture of
      human pulmonary fibroblasts: role of dimension and rigidity.
AB  - Pulmonary fibrosis is a poorly understood pathologic condition. Carbon nanotubes
      (CNTs) are nanomaterials with potentials for broad applications. CNTs can induce
      pulmonary fibrosis in animals, a cause for concern for exposed workers and
      consumers. Given the large number of CNTs available on the market and the
      seemingly infinite number of ways these particles can be modified in ways that
      may affect toxicity, in vitro models that can be used to quickly and effectively
      investigate the relative fibrogenicity of CNTs are much needed. Here we analyzed
      the fibrogenic potentials of six CNTs of varying physical properties and
      crystalline silica using two- and three-dimensional (2D and 3D, respectively) in
      vitro models. WI38-VA13 human pulmonary fibroblasts were treated with CNTs or
      silica, with TGF-beta1, a known inducer of fibroblast differentiation, as
      positive control. The cells were examined for fibrotic matrix alterations,
      including myofibroblast transformation, matrix remodeling, and matrix
      contraction. While all tested CNTs induced myofibroblast differentiation in 2D
      and 3D cultures, the 3D culture allowed the examination of myofibroblast
      clustering, collagen deposition and rearrangement, cell division, and matrix
      contraction in response to fibrogenic exposures, processes critical for fibrosis
      in vivo. At 1 ug/ml, MWCNTs elicit higher induction of myofibroblast
      differentiation and matrix remodeling than SWCNTs. Among MWCNTs, those with the
      highest and lowest aspect ratios produced the largest effects, which were
      comparable to those by TGF-beta1 and higher than those by silica. Thus, the 3D
      collagen-based model enables the study of matrix fibrotic processes induced by
      CNTs and silica particles directly and effectively.

PMID- 30229331
TI  - A serum metabolomics signature of hypothermia fatalities involving arginase
      activity, tryptophan content, and phosphatidylcholine saturation.
AB  - INTRODUCTION: Hypothermia is a potentially lethal condition whose postmortem
      diagnosis is often complex to perform due to the absence of pathognomonic lesions
      and biomarkers. Our first study of human serum and urinary metabolome in
      hypothermia fatalities sought novel biomarkers with better diagnostic
      performances than those already existing. MATERIAL AND METHOD: Thirty-two cases
      of hypothermia deaths and 16 cases excluding known antemortem exposure to cold or
      postmortem elements suggesting hypothermia were selected. A targeted metabolomic
      study allowing the detection and quantitation of 188 metabolites was performed on
      collected serum and urine using direct flow injection (FIA) and liquid
      chromatography (LC) separation, both coupled to tandem mass spectrometry (MS/MS).
      Amino acid quantification was also carried on using an in-house LC-MS/MS method
      in order to replicate the results obtained with the metabolomic study. RESULTS: A
      discriminant metabolic signature allowing a clear separation between hypothermia
      and control groups was obtained in the serum. This signature was characterized by
      increased arginase activity and fatty acid unsaturation along with decreased
      levels of tryptophan in hypothermia fatalities compared to controls. By contrast,
      no discriminant metabolic signature separating hypothermia from control
      fatalities was found in urines. DISCUSSION: The serum metabolic signature of
      hypothermia fatalities herein observed pointed toward metabolic adaptations that
      likely aimed at heat production enhancement, endothelial function, and cell
      membrane fluidity preservation. Novel biomarkers potentially useful in a
      hypothermia diagnosis were also identified.

PMID- 30229332
TI  - Effective resolution of the Y chromosome sublineages of the Iberian haplogroup
      R1b-DF27 with forensic purposes.
AB  - Single-nucleotide polymorphisms (SNPs) found within the non-recombining region of
      the Y chromosome (NRY) represent a powerful tool in forensic genetics for
      inferring the paternal ancestry of a vestige and complement the determination of
      biogeographical origin in combination with other markers like AIMs. In the
      present study, we introduce a panel of 15 Y-SNPs for a fine-resolution subtyping
      of the haplogroup R1b-DF27, in a single minisequencing reaction. This is the
      first minisequencing panel that allows a fine subtyping of R1b-DF27, which
      displays high frequencies in Iberian and Iberian-influenced populations. This
      panel includes subhaplogroups of DF27 that display moderate geographical
      differentiation, of interest to link a sample with a specific location of the
      Iberian Peninsula or with Iberian ancestry. Conversely, part of the intricacy of
      a new minisequencing panel is to have all the included variants available to test
      the effectiveness of the analysis method. We have overcome the absence of the
      least common variants through site-directed mutagenesis. Overall, the results
      show that our panel is a robust and effective method for subtyping R1b-DF27
      lineages from a minimal amount of DNA, and its high resolution enables to improve
      male lineage discrimination in Iberian and Southwest European descent
      individuals. The small length of the amplicons and its reproducibility makes this
      assay suitable for forensic and population genetics purposes.

PMID- 30229333
TI  - [Reduction the risk in pediatric anesthesia-what should we know-what should we
      do].
AB  - Pediatric anesthesia has always been conjuncted with higher risk than anesthesia
      for adults (JP Morray; Pediatric Anesthesia 2011;21:722-9). Not only the imminent
      critical events, but also, caused by recently published data, the theoretical
      neurotoxicity of anesthetic agents and a potencial negative influence of
      anesthetics on braindevelopement, are in the spotlight.Concerns about the
      neurodevelopement and the general warnings from the U.S. Food and Drug
      Administration (FDA) for anesthesia in young children led to a worldwide
      discussion about safety in pediatric anesthesia (FDA Safety Anouncement
      2017).Beside these theoretical risks, which are based only on animal research, we
      have to pay much more attention to the widely spread out poor quality of
      anesthesia in children.The following article should summarize the state of
      science about the risks and the opportunities to minimize them.

PMID- 30229334
TI  - [Examination facility at Hannover Medical School].
AB  - Dissection of the examination system of Hannover Medical School has identified
      potential for improvement of the complete procudere. Five scopes has been
      identified: 1. advancement of electronic examinations, 2. improvement of quality
      control, 3. central management of all exams, 4. more transperancy, 5.
      establishment of an incentive structure. The strategies for improvement were
      presented.

PMID- 30229335
TI  - [Quality criteria for academic assessments according to Kane's framework].
AB  - Although the publication of the recommendations of GMA and MFT in 2014 concerning
      the improvement of assessment quality in medical education had been an important
      step for the German-speaking faculties, it is still necessary to increase the
      efforts. There are still some aspects of assessments which were only intimated by
      the recommendations.Kane's framework for the validation of tests, published in
      2013, is of special importance for assessments within medical studies. But the
      application of this framework hasn't been consequent enough until now. The
      article tries to give an indirect, general answer to the question, what has to be
      considered, when assessments in medical education were planned.

PMID- 30229336
TI  - Substantial renal conversion of L-threo-3,4-dihydroxyphenylserine (droxidopa) to
      norepinephrine in patients with neurogenic orthostatic hypotension.
AB  - BACKGROUND: The pressor effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS,
      droxidopa, NortheraTM) results from conversion of L-DOPS to norepinephrine (NE)
      in cells expressing L-aromatic-amino-acid decarboxylase (LAAAD). After L-DOPS
      administration the increase in systemic plasma NE is too small to explain the
      increase in blood pressure. Renal proximal tubular cells abundantly express
      LAAAD. Since NE generated locally in the kidneys could contribute to the pressor
      effect of L-DOPS, in this study we assessed renal conversion of L-DOPS to NE.
      METHODS: Ten patients who were taking L-DOPS for symptomatic orthostatic
      hypotension had blood and urine sampled about 2 h after the last L-DOPS dose. L
      DOPS and NE were assayed by alumina extraction followed by liquid chromatography
      with electrochemical detection. Data were compared in patients off vs. on
      levodopa/carbidopa. RESULTS: In patients off levodopa/carbidopa the ratio of NE/L
      DOPS in urine averaged 63 times that in plasma (p = 0.0009 by t test applied to
      log-transformed data). In marked contrast, in the three patients on
      levodopa/carbidopa the ratio of NE/L-DOPS in urine did not differ from that in
      plasma. CONCLUSION: There is extensive renal production of NE from L-DOPS.
      Carbidopa seems to attenuate the conversion of L-DOPS to NE in the kidneys.
      Further research is needed to assess whether the proposed paracrine effect of L
      DOPS in the kidneys contributes to the systemic pressor response.

PMID- 30229337
TI  - Long-term follow-up after rib fixation for flail chest and multiple rib
      fractures.
AB  - PURPOSE: Rib fixation for flail chest has been shown to improve in-hospital
      outcome, but little is known about treatment for multiple rib fractures and long
      term outcome is scarce. The aim of this study was to describe the safety, long
      term quality of life, and implant-related irritation after rib fixation for flail
      chest and multiple rib fractures. METHODS: All adult patients with blunt thoracic
      trauma who underwent rib fixation for flail chest or multiple rib fractures
      between January 2010 and December 2016 in our level 1 trauma facility were
      retrospectively included. In-hospital characteristics and implant removal were
      obtained via medical records and long-term quality of life was assessed over the
      telephone. RESULTS: Of the 864 patients admitted with >= 3 rib fractures, 166
      (19%) underwent rib fixation; 66 flail chest patients and 99 multiple rib
      fracture patients with an ISS of 24 (IQR 18-34) and 21 (IQR 16-29), respectively.
      Overall, the most common complication was pneumonia (n = 58, 35%). Six (9%)
      patients with a flail chest and three (3%) with multiple rib fractures died, only
      one because of injuries related to the thorax. On average at 3.9 years, follow-up
      was obtained from 103 patients (62%); 40 with flail chest and 63 with multiple
      rib fractures reported an EQ-5D index of 0.85 (IQR 0.62-1) and 0.79 (0.62-0.91),
      respectively. Forty-eight (48%) patients had implant-related irritation and nine
      (9%) had implant removal. CONCLUSIONS: We show that rib fixation is a safe
      procedure and that patients reported a relative good quality of life. Patients
      should be counseled that after rib fixation approximately half of the patients
      will experience implant-related irritation and about one in ten patients requires
      implant material removal.

PMID- 30229338
TI  - Contrast-induced nephropathy following CT scan for trauma is not rare and is
      associated with increased mortality in South African trauma patients.
AB  - PURPOSE: Acute trauma patients are at risk for the development of acute kidney
      injury (AKI). One potential nephrotoxic agent, which a trauma patient may be
      exposed to, is iodinated contrast media (ICM). We aim to review the incidence and
      outcome of contrast-induced nephropathy (CIN) in trauma patients in a busy trauma
      service, and to identify potentially modifiable risk factors. METHODS: During the
      period from December 2012 to April 2017, all patients who underwent a contrast
      enhanced CT scan for trauma were included. Data were examined and outcome data
      were reviewed. RESULTS: A total of 1566 patients required a CT scan following
      blunt trauma at our institution. Of this total 755 patients underwent a contrast
      enhanced CT scan. There were 173 females (22.9%) and 582 males (77.1%). All these
      patients received intravenous contrast. A total of 143 (18.9%) were admitted to
      ICU, and 58 (7.7%) of patients died. Detailed electrolyte studies pre- and post
      procedure were available for 312 patients. Of these 312 patients, 46 developed
      CIN (14.7%).There was no difference in the incidence of pre-CT AKI or deranged
      electrolytes between the patients who developed CIN and those who did not. The
      development of CIN was associated with an increased risk of death as well as
      increased need for renal replacement therapy as well as increased need for ICU.
      CONCLUSION: Contrast-induced nephropathy is a real risk in trauma patients
      undergoing contrast-enhanced CT scan for blunt trauma in our environment. Further
      work is needed to define and delineate risk factors.

PMID- 30229339
TI  - Prognostic evaluation in palliative care: final results from a prospective cohort
      study.
AB  - Prognostic characterization in the initial assessment of patients with advanced
      cancer disease is an essential step to plan the most appropriate therapeutic
      program. Since clinical prediction of survival (CPS) may be of limited value,
      some authors have tried to integrate specific prognostic factors into prognostic
      multidimensional scores. We carried out a prospective cohort study in two
      palliative care units to compare the accuracy of the Palliative Prognostic (PaP)
      Score, the Objective Prognostic Score (OPS), and the Palliative Prognostic Index
      (PPI). In addition, we compared the accuracy of the CPS independently estimated
      by different healthcare professionals and we tested the role of laboratory
      results, together with clinical and social factors in predicting survival.
      Clinical and laboratory data of 334 advanced cancer patients were prospectively
      collected from the time of in-hospital admission. PaP Score was the most accurate
      index of survival prediction, followed by PPI; CPS estimates' accuracy was
      similar among physicians and nurse. All healthcare professionals tended to
      underestimate the real survival. Integrating CPS with multidimensional indexes
      may further improve the patient's management. The degree of autonomy and the
      number of metastatic sites were independent prognostic factors for 30-days
      mortality and overall survival in multivariate analysis.

PMID- 30229340
TI  - Grandparents of children with cancer: a controlled comparison of perceived family
      functioning.
AB  - PURPOSE: Grandparents can be profoundly emotionally affected when a grandchild is
      diagnosed with cancer. They also often provide invaluable support for the family
      (e.g., caring for the sick child and/or siblings). Multigenerational family
      functioning may therefore change. Limited research has assessed grandparents'
      perspectives after their grandchild is diagnosed with cancer. In this study, we
      aimed to (1) assess differences in perceived family functioning among
      grandparents of a child with cancer and grandparents of healthy children and (2)
      assess the cancer-specific and demographic factors related to perceived family
      functioning in grandparents of a grandchild with cancer. PROCEDURE: Grandparents
      of a child with cancer (n = 89) and grandparents of healthy children (n = 133)
      completed the general functioning, communication, and problem-solving scales of
      the Family Assessment Device. We used multilevel models with a random intercept
      to detect (1) between-group differences and (2) identify factors related to
      perceived family functioning among grandparents with a grandchild with cancer.
      RESULTS: Grandparents with a grandchild with cancer reported poorer family
      functioning than grandparents with healthy grandchildren. Among the grandparents
      with a grandchild with cancer, impairments in family functioning were correlated
      with fewer years since diagnosis, providing care to their sick grandchild and/or
      siblings and living far away from the sick grandchild. CONCLUSIONS: The
      detrimental impact of childhood cancer likely extends beyond the immediate family
      members. Including grandparents in interventions-beginning at diagnosis-to reduce
      distress and increase cohesion for families of a child with cancer is warranted,
      particularly for grandparents who provide care to their sick grandchild or
      siblings.

PMID- 30229341
TI  - Preliminary results of a novel spacer technique in the management of septic
      revision hip arthroplasty.
AB  - INTRODUCTION: Mechanical failure due to dislocation, fracture and acetabular wear
      is a major complication associated with the use of spacers in the management of
      periprosthetic joint infection (PJI). We have developed a novel custom-made
      spacer in the setting of two-stage septic revision hip arthroplasty and present
      the preliminary results of our technique. MATERIALS AND METHODS: Between May 2015
      and November 2017, 30 patients underwent hip revision using the ENDO spacer
      technique in the setting of a two-stage septic exchange arthroplasty. The
      technique involves the dual mobility liner and the downsized stainless cemented
      straight stem in combination with antibiotic-loaded PMMA bone cement. The primary
      outcome measure was the overall spacer complication rate, particularly spacer
      dislocation. Furthermore, functional outcome using the Harris Hip Score (HHS)
      before spacer implantation and prior re-implantation was evaluated. RESULTS: The
      mean age of the patients was 69.8 years (range from 45 to 85; SD = 9.9 years). No
      microorganisms were preoperatively found in 23 (76.7%) cases. Successful re
      implantation was performed in all patients after a mean spacer duration time of
      53.6 days (range 14-288 days; SD = 48.2). Spacer-related complications occurred
      in only two patients (6.7%). The HHS significantly improved from 34.0 (range 3
      62; SD = 15.1) to 48.1 (range 11-73; SD = 15.7) (p = 0.0008). CONCLUSIONS: The
      ENDO spacer surgical technique is a feasible option in the treatment of
      periprosthetic joint infection (PJI), with a low dislocation rate. Furthermore,
      it allows early mobilization with the possibility of full-weight bearing.

PMID- 30229342
TI  - Return to car driving is safe 6 weeks after operative treatment of right ankle
      fractures.
AB  - BACKGROUND: There is no clear consensus on when patients with surgically treated
      right ankle fractures can return to car driving, or how best to assess their
      fitness to drive. Through a rigorous driving assessment program consisting of
      both off-road and on-road tests, we aim to determine if these patients are able
      to pass a standard driving test, even before weight bearing has been initiated.
      METHODS: A prospective grant-funded (Supported by AOTrauma Asia Pacific Ref:
      AOTAP12-17) clinical study was conducted. Patients aged 25-65 years who underwent
      surgery for right ankle fractures and held a valid motorcar driving license were
      recruited in a single institution from 2013 to 2015. The surgeon and a specialist
      occupational therapist assessed the patients at 2, 6 and 12 weeks post-surgery. A
      Short Musculoskeletal Functional Assessment (SMFA) Questionnaire was administered
      and the brake reaction time was measured using a driving simulator. Patients who
      met the minimal criteria were then subjected to a full on-road driving test in a
      real-world environment with a driving instructor. A follow-up telephone
      questionnaire was administered at least 6 months after return to driving to
      determine if patients had returned to driving safely. RESULTS: A total of 23
      patients (8 females, 15 males) were recruited. The mean age was 42.8 (+/- 12.9)
      years. There was a significant improvement in the SMFA (p < 0.05) and braking
      time (p < 0.05) at 6 and 12 weeks post-surgery. Nearly all (91%) patients passed
      the on-road driving test at 6 weeks, before their fractures had healed or weight
      bearing was initiated. The questionnaire administered at least 6 months after
      return to driving revealed that all patients had returned to regular driving
      safely. CONCLUSION: We conclude that patients with isolated, surgically treated
      right ankle fractures can successfully pass a standard driving test at 6 weeks
      post-surgery, even before weight bearing has been initiated. We also showed that
      the ability to drive correlates with improvements in the SMFA scores and braking
      times. LEVEL OF EVIDENCE: II.

PMID- 30229343
TI  - Technology Delivered Interventions for Depression and Anxiety in Children and
      Adolescents: A Systematic Review and Meta-analysis.
AB  - Depression and anxiety are common during adolescence. Whilst effective
      interventions are available treatment services are limited resulting in many
      adolescents being unable to access effective help. Delivering mental health
      interventions via technology, such as computers or the internet, offers one
      potential way to increase access to psychological treatment. The aim of this
      systematic review and meta-analysis was to update previous work and investigate
      the current evidence for the effect of technology delivered interventions for
      children and adolescents (aged up to 18 years) with depression and anxiety. A
      systematic search of eight electronic databases identified 34 randomized
      controlled trials involving 3113 children and young people aged 6-18. The trials
      evaluated computerized and internet cognitive behavior therapy programs (CBT: n =
      17), computer-delivered attention bias modification programs (ABM: n = 8)
      cognitive bias modification programs (CBM: n = 3) and other interventions (n =
      6). Our results demonstrated a small effect in favor of technology delivered
      interventions compared to a waiting list control group: g = 0.45 [95% CI 0.29,
      0.60] p < 0.001. CBT interventions yielded a medium effect size (n = 17, g = 0.66
      [95% CI 0.42-0.90] p < 0.001). ABM interventions yielded a small effect size (n =
      8, g = 0.41 [95%CI 0.08-0.73] p < 0.01). CBM and 'other' interventions failed to
      demonstrate a significant benefit over control groups. Type of control condition,
      problem severity, therapeutic support, parental support, and continuation of
      other ongoing treatment significantly influenced effect sizes. Our findings
      suggest there is a benefit in using CBT based technology delivered interventions
      where access to traditional psychotherapies is limited or delayed.

PMID- 30229344
TI  - Reproducibility of global left atrial strain and strain rate between novice and
      expert using multi-vendor analysis software.
AB  - Left atrial (LA) strain is an emerging technique with potential applications
      including arrhythmia prediction in atrial fibrillation and early identification
      of atrial dysfunction. The aim of this study was to evaluate reproducibility of
      LA strain and strain rate (SR) using multi-vendor analysis software between
      novice and expert. For LA strain to be a reliable tool, the technique must be
      reproducible by observers with variable experience. Use of multi-vendor analysis
      software allows serial strain assessment when echocardiographic images are
      acquired using different vendors. Fifty subjects underwent 2D-Speckle tracking
      echocardiographic (STE) derived LA strain and SR analysis measured from apical
      four and two-chamber views. Three strain parameters of LA function were assessed:
      reservoir (S-LAs, SR-LAs), contractile (S-LAa, SR-LAa) and conduit (S-LAs-S-LAa,
      SR-LAe). Strain analyses were performed by 2 independent, blinded novice and
      expert observers using multi-vendor analysis software. Intraobserver and
      interobserver analyses were performed using intra class correlation coefficients
      (ICC) and Bland-Altman analysis. LA strain and SR measured by novice observer
      demonstrated excellent intraobserver reproducibility (ICC for all strain and SR
      values > 0.88). There was good interobserver agreement of LA strain values
      between novice and expert (S-LAs:ICC 0.81, S-LAe:ICC 0.82, S-LAa:ICC 0.74). SR
      values also demonstrated good interobserver agreement (SR-LAs:ICC 0.83, SR
      LAe:ICC 0.79, SR-LAa:ICC 0.86). Of all parameters, SR-LAa had the best
      interobserver and intraobserver agreement (ICC 0.86, 0.96). Global LA strain and
      SR values were highly reproducible by novice strain reader using multi-vendor
      analysis software. Interobserver reproducibility between novice and experts were
      good and acceptable within limits of agreement.

PMID- 30229345
TI  - Calcium sustained release, pH changes and cell viability induced by chitosan
      based pastes for apexification.
AB  - We explored chitosan-based sustained release pastes for apexification. The study
      aimed to formulate chitosan-based pastes loaded with calcium hydroxide (CH) or
      with calcium chloride (CC), and to evaluate the sustained release of Ca2+ and pH
      changes in deionized water as well as the effect of the pastes on cell viability.
      The pastes were formulated by dissolution of the chitosan in 1% or 2% acetic acid
      (AAC) plus the addition of CH or CC, then were suspended in deionized water for
      50 days; the released Ca(II) and pH were measured with an electrode probe. The
      effect of the pastes on viability of human dental pulp cells was evaluated with a
      MTS assay. The results showed that the pastes prepared with 1% and 2% AAC and
      loaded with CH released a 74.9% and a 76.1% of the Ca2+ content, respectively,
      while the pastes prepared with 1% and 2% AAC loaded with CC released a content of
      Ca2+ of 90.8% and 76.6%, respectively. A control paste (CH and polyethylene
      glycol) released a 95.4%; significant statistical differences were found between
      the percentage of the experimental pastes and the control. The CH-loaded pastes
      caused an alkaline pH at the starting of the study, but the pH became neutral at
      the ending. The pH of the CC-loaded pastes was neutral at the starting and was
      acid at the ending. The pastes no affected on the cell viability. The chitosan
      based pastes showed a suitable sustained release profile and cytocompatibility.

PMID- 30229346
TI  - Effects and parameters of the photobiomodulation in experimental models of third
      degree burn: systematic review.
AB  - This systematic review was performed to identify the role of photobiomodulation
      therapy in experimental models of third-degree burns used to induce oxidative
      stress. EMBASE, PubMed, and CINAHL databases were searched for studies published
      between January 2003 and January 2018 on the topics of photobiomodulation therapy
      and third-degree burns. Any study that assessed the effects of photobiomodulation
      therapy in animal models of third-degree burns was included in the analysis. A
      total of 17 studies were selected from 1182 original articles targeted on
      photobiomodulation therapy and third-degree burns. Two independent raters with a
      structured tool for rating the research quality critically assessed the articles.
      Although the small number of studies limits the conclusions, the current
      literature research indicates that photobiomodulation therapy can be an effective
      short-term approach to accelerate the healing process of third-degree burns, to
      increase and modulate the inflammatory process, to accelerate the proliferation
      of fibroblasts, and to enhance the quality of the collagen network. However,
      differences still exist in the terminology used to describe the parameters and
      the dose of photobiomodulation therapy.

PMID- 30229347
TI  - The Management of Depressed Patients by the Tunisian General Practitioners: A
      Critical Trans-sectional Study.
AB  - Under-diagnosed and under-treated, depression has a pejorative prognosis. The
      general practitioners (GP) represent the most often consulted healthcare
      professionals by depressed patients. The aim was to describe how the Tunisian GPs
      manage the depressed patients and to note the difficulties they encounter in
      order to suggest corrective measures. A survey was conducted among 140 GPs in
      Sfax Governorate. The percentage of the GPs whose responses conformed to the
      scientific data in at least 67% of the items was 31.4%. Four factors were
      correlated to a good management of depression: age (p = 0.028), masculine gender
      (p = 0.016), long career (p = 0.034) and participation to continuous medical
      education sessions on depression (p = 0.01). Our study revealed inadequacies in
      the management of depression by the GPs. GPs were invited to sensitizing
      meetings. A training on depression was assured for the future internship
      supervisors by the commission of medicine of family in the Faculty of Medicine of
      Sfax.

PMID- 30229348
TI  - Desmoplastic fibroblastoma mimicking tenosynovial giant cell tumor encasing a
      tendon of the foot.
AB  - Desmoplastic fibroblastoma is an uncommon, benign fibrous soft tissue tumor that
      usually occurs in the arms, shoulders, neck, hands, and feet in the fifth to
      seventh decades of life. In general, it is commonly located in the subcutaneous
      tissue and skeletal muscle. The authors report an unusual case of a desmoplastic
      fibroblastoma mimicking tenosynovial giant cell tumor encasing a tendon of the
      foot in a 72-year-old woman. Ultrasonography revealed an inhomogeneously
      hypoechoic lobulated soft tissue lesion completely wrapped around the extensor
      digitorum longus tendon. Color Doppler study revealed increased vascularity in
      the internal and peripheral portions of the lesion. Magnetic resonance imaging
      revealed a well-defined, lobulated soft tissue mass encasing the extensor
      digitorum longus tendon with predominantly isointense signal with some areas of
      hypointense signal on T1-weighted images, predominantly hyperintense signal with
      some areas of hypointense signal on T2-weighted images, and inhomogeneous
      enhancement on fat-suppressed contrast-enhanced T1-weighted images. Surgical
      excision was performed, and the mass was diagnosed on pathological examination as
      a desmoplastic fibroblastoma. There has been no previously published radiologic
      case of a desmoplastic fibroblastoma encasing a tendon of the foot in the
      literature.

PMID- 30229349
TI  - Genetic validation study of protein tyrosine phosphatase receptor type D (PTPRD)
      gene variants and risk for antipsychotic-induced weight gain.
AB  - Schizophrenia is a severe, debilitating disorder with a lifetime prevalence of 1%
      irrespective of gender or ethnicity and is typically treated with antipsychotic
      drugs. Antipsychotic-induced weight gain (AIWG) is a leading factor of patient
      non-compliance and has previously been shown to increase the risk of type 2
      diabetes, metabolic syndrome, and cardiovascular events. The current study
      intends to replicate findings from a recent genome-wide association study in Han
      Chinese patients implicating two gene variants (rs10977144 and rs10977154) of the
      protein tyrosine phosphatase receptor type D (PTPRD) in antipsychotic-induced
      weight gain (AIWG). We investigated a sample of European and African American
      ancestry (n = 201) and calculated percentage of weight change using linear
      regression corrected for type of antipsychotics, duration of treatment and
      principal components from ancestry checks. As secondary goal, we investigated
      additional gene variants of PTPRD previously not associated with AIWG. We found
      no association with rs10977144 and rs10977154. However, we found nominally
      significant results between PTPRD and AIWG with rs73398242 in Europeans (BETA = -
      0.267, p = 0.002) and rs13294608 in African Americans (BETA = 0.423, p = 0.003).
      According to Haploreg, both SNPs are histone marks for enhancers and promoters
      across various brain regions including the cingulate gyrus and dorsolateral
      prefrontal cortex. In summary, our results tentatively suggest that PTPRD might
      be associated with AIWG although different SNPS might be involved in different
      ethnic groups.

PMID- 30229350
TI  - Structural aspects of human lactoferrin in the iron-binding process studied by
      molecular dynamics and small-angle neutron scattering.
AB  - Lactoferrin is a non-heme protein known for its ability to bind tightly Fe(III)
      ions in various physiological environments. Due to this feature lactoferrin plays
      an important role in the processes of iron regulation at the cellular level
      preventing the body from damages produced by high levels of free iron ions. The X
      ray crystal structure of human lactoferrin shows that the iron-binding process
      leads to conformational changes within the protein structure. The present study
      was addressed to conformation stability of human lactoferrin in solution. Using
      molecular dynamics simulations, it was shown that Arg121 is the key amino acid in
      the stabilization of the Fe(III) ion in the N-lobe of human lactoferrin. The
      small-angle neutron scattering method allowed us to detect the structural
      differences between the open and closed conformation of human lactoferrin in
      solution. Our results indicate that the radius of gyration of apolactoferrin
      appears to be smaller than that of the hololactoferrin, [Formula: see text] A and
      [Formula: see text] A, respectively. The low-resolution three-dimensional models
      computed for both forms of human lactoferrin in solution also show visible
      differences, both having a more compact conformation compared to the high
      resolution structure.

PMID- 30229352
TI  - Cardiovascular Outcomes Trials Update: Insights from the DEVOTE Trial.
AB  - PURPOSE OF REVIEW: The DEVOTE study compared the cardiovascular safety of two
      basal insulins, degludec, and glargine U100 in patients with type 2 diabetes
      (T2D) at high risk for cardiovascular disease (CVD). In this review, we summarize
      the results of DEVOTE and provide a clinical perspective. RECENT FINDINGS: DEVOTE
      was a phase 3b, multicenter, international, treat-to-target, double-blind, event
      driven trial. Patients with T2D > 50 years of age with prior CVD or > 60 years of
      age with CVD risk factors were randomly assigned to receive either degludec (n =
      3818) or insulin glargine U100 (n = 3819) and were followed until at least 633
      positively adjudicated major adverse cardiovascular events (MACE; cardiovascular
      death, nonfatal myocardial infarction, or nonfatal stroke) accrued. At baseline,
      the mean age of the subjects was 65.0 years, the mean duration of diabetes was
      16.4 years, and the mean HbA1c was 8.4 +/- 1.7%. After a median follow-up of 2
      years, HbA1c had decreased to 7.5 +/- 1.2% in each group. Degludec was non
      inferior to insulin glargine U100 with respect to the primary MACE outcome
      (hazard ratio 0.91; 95% CI 0.78-1.06). Significantly, lower rates of severe
      hypoglycemia and nocturnal severe hypoglycemia were observed with degludec
      compared to glargine U100 (rate ratios of 0.60; 95% CI 0.48-0.76 and 0.47; 95% CI
      0.31 to 0.73, respectively). DEVOTE demonstrated that the cardiovascular safety
      of degludec was comparable to that of insulin glargine U100 in patients with T2D
      at high risk for CVD. Additionally, degludec was superior to insulin glargine
      U100 with respect to the risk for severe hypoglycemia. These results suggest that
      degludec might be preferred in patients at risk for severe hypoglycemia,
      including the elderly, those with CVD and/or those with chronic kidney disease.

PMID- 30229353
TI  - Cell culture medium supplemented with taurine decreases basic charge variant
      levels of a monoclonal antibody.
AB  - OBJECTIVE: To explore the impact of taurine on monoclonal antibody (mAb) basic
      charge variants in Chinese hamster ovary (CHO) cell culture. RESULTS: In fed
      batch culture, adding taurine in the feed medium slightly increased the maximum
      viable cell density and mAb titers in CHO cells. What's more, taurine
      significantly decreased the lysine variant and oxidized variant levels, which
      further decreased basic variant contents from 32 to 27%. The lysine variant
      content in the taurine culture was approximately 4% lower than that in control
      condition, which was the main reason for the decrease in basic variants. Real
      time PCR and cell-free assay revealed that taurine played a critical role in the
      upregulation of relative basic carboxypeptidase and stimulating extracellular
      basic carboxypeptidase activities. CONCLUSION: Taurine exhibits noticeable impact
      on lower basic charge variants, which are mainly due to the decrease of lysine
      variant and oxidized protein variants.

PMID- 30229351
TI  - Issues in Defining the Burden of Prediabetes Globally.
AB  - PURPOSE OF REVIEW: Using a global perspective, this review collates evidence on
      the heterogeneity of prediabetes definitions and diagnostic methods, their
      clinical and public health implications, and discusses possible options for
      improvement. RECENT FINDINGS: Our review notes that the concept of prediabetes is
      increasingly recognized worldwide, but against a background of non-uniform
      definition and diagnostic criteria. This results in widely varying burden
      estimation. Current evidence shows a variety of prediabetes phenotypes. This
      reflects biological and diagnostic heterogeneity, resulting from the use of
      different tests (glucose or HbA1C) and thresholds to define prediabetes. The
      biological and diagnostic variabilities have implications for the
      characterization of the burden of prediabetes, natural history, prognosis,
      screening, implementation of lifestyle or drug interventions to mitigate related
      health risks, and monitoring of the effects of such interventions.

PMID- 30229354
TI  - Eat whole and less often: ontogenetic shift reveals size specialization on kelp
      bass by the California moray eel, Gymnothorax mordax.
AB  - Despite the importance of predation in many ecosystems, gaps remain in our
      understanding of nocturnal marine predators. Although the kelp forests of
      Southern California are some of the most well-studied ecosystems, California
      morays, Gymnothorax mordax, are predominately nocturnal predators that have
      remained largely unstudied and their predatory effects on the kelp forest
      ecosystem are unknown. We use a multi-year data set to examine the dietary
      breadth of G. mordax and to determine the functional role of this predator. We
      also quantify bite force to examine the potential performance limitations of
      morays in exploiting prey. Stomach content analyses and linear selectivity index
      values indicate that G. mordax specializes on kelp bass, Paralabrax clathratus.
      Average size of kelp bass consumed varies across years, suggesting that morays
      respond to fluctuations in prey size availability. The scaling relationship of
      kelp bass standard length and moray head length reveals an ontogenetic shift,
      where maximum prey size increases with moray size and small prey are dropped from
      the diet of larger individuals. Moray bite force exhibited strong positive
      allometry with moray head size, suggesting that larger morays exhibit greater
      bite forces for their head and body size. However, we found no relationship
      between prey size and bite force, suggesting that a disproportional increase in
      bite force does not facilitate the consumption of disproportionately larger prey.
      Our results indicate that while G. mordax of Catalina Island is a dietary
      specialist, it is capable of exhibiting functional shifts in prey size and
      species based on their abundance.

PMID- 30229355
TI  - Novel Floral Scent Compounds from Night-Blooming Araceae Pollinated by
      Cyclocephaline Scarabs (Melolonthidae, Cyclocephalini).
AB  - Nocturnal flowering plants often release strong scents to attract their
      pollinators. Among night active flower visitors are cyclocephaline scarab
      beetles, which have been demonstrated to respond to uncommon volatile organic
      compounds released in high amounts by their host plants. In Araceae, the
      molecular structure of several such compounds is yet to be unveiled. We
      investigated headspace floral scent samples of Philodendron squamiferum,
      Thaumatophyllum mello-baretoanum, and Xanthosoma hylaeae by a variety of
      approaches, leading to the identification of novel compounds. Dehydrojasmone, (Z)
      4-methylene-5-(pent-2-en-1-yl)cyclopent-2-en-1-one (1), (Z)-3-methylene-2-(pent-2
      en-1-yl)cyclopentyl acetate (isojasmyl acetate, 3), and (E)-4,8-dimethylnona
      1,3,7-trien-5-yl acetate (4) had not been previously reported, while full
      analytical data of the recently described (Z)-3-methylene-2-(pent-2-en-1
      yl)cyclopentan-1-ol (isojasmol, 2) are presented here. All these compounds are
      derived from more common precursors, (Z)-jasmone and (E)-4,8-dimethyl-1,3,7
      nonatriene, likely through biosynthetic "post-processing".

PMID- 30229356
TI  - Boron-nitrogen dative bond.
AB  - This study consists of the theoretical analysis of some organic molecules and
      their inorganic similar compounds, through substitution of two carbon atoms by
      boron and nitrogen atoms. The methods DFT/B3-LYP/TZVPP and CC2/TZVPP were
      considered. Firstly, ethane, ethene, and ethyne molecules (based on C atoms and
      their BN/NB analogs) were studied. These molecules were considered as a reference
      for the analysis of other molecules with functional groups. These molecules with
      functional groups are: ethanol, ethanal (and its isomer ethenol), ethanoic acid
      (and its isomer ethenediol), ethylamine, ethylbenzene, propane, and fluoroethane.
      We studied the energies, bond length, population analysis, and bond order. The
      dative bonds (BN) are bigger and weaker than that covalent based on C atoms. The
      dative bond has pi character when the BN bond is double and triple. It is
      possible to distinguish two different behaviors for BN bonds, one when the
      functional group is bounded to the B atom, and the other to the N atom. When the
      functional group is bounded to the B atom, the BN bond is weaker and lengthier
      than that when the same group is bounded to the N atom. However, the isomer with
      weaker BN bond is the most stable one. Graphical abstract Comparative studies of
      dative bonds among substituted inorganic molecules, e.g., BN-ethanol, show
      important differences in terms of length and energy in comparison to organic
      analogous. There is also a difference when comparing BN or NB molecules
      (according to witch atom the functional group is bonded to, B or N); bond length,
      for example, is bigger for BN molecules.

PMID- 30229357
TI  - In risk we trust/Editing embryos and mirroring future risks and uncertainties.
AB  - Tendencies and efforts have shifted from genome description, DNA mapping, and DNA
      sequencing to active and profound re-programming, repairing life on genetic and
      molecular levels in some parts of contemporary life science research. Mirroring
      and materializing this atmosphere, various life engineering technologies have
      been used and established in many areas of life sciences in the last decades. A
      contemporary progressive example of one such technology is DNA editing. Novel
      developments related to reproductive technologies, particularly embryo editing,
      prenatal human life engineering, and germline engineering need to be analyzed
      against the broader social and structural background. The crucial analytical
      scope for this paper is a specific field: the life-editing technologies used in
      reproductive medicine and performed experimentally on viable human embryos,
      particularly CRISPR/Cas9 technology. This text argues that germline editing
      technologies, as a representative part of contemporary biomedicine, are merging
      ideas of treatment and enhancement to avoid future risks. Using this specific
      life manipulation of embryos and gametes, the text analyzes these processes
      within the concept of power over life-biopower and the specific governing
      rationality that imagines, classifies, and governs contemporary societies. The
      text specifically focuses on the potential to create, define, and manage future
      risks and uncertainties related to prenatal life.

PMID- 30229359
TI  - Decreasing Food Stealing of Child with Prader-Willi Syndrome Through Function
      Based Differential Reinforcement.
AB  - Challenging behaviors involving food are common for individuals with Prader-Willi
      syndrome (PWS) and often lead to obesity and other chronic health conditions.
      Efforts to decrease these behaviors, such as isolation during meals and strict
      monitoring of food consumption, can be stigmatizing. To decrease the food
      stealing of a 7 year-old girl with PWS, therapists conducted a latency-based
      functional analysis in a clinic setting before implementing a function-based
      intervention to facilitate her inclusion at the family dinner table. Intervention
      components entailed differential reinforcement procedures which incorporated a
      token board and schedule thinning. The intervention successfully generalized to
      the home setting and across food preferences and implementers.

PMID- 30229360
TI  - The Role of Grandparents in Supporting Families of Children with Autism Spectrum
      Disorders: A Family Systems Approach.
AB  - A family systems approach is required to identify the needs of families of
      children with autism. This paper explores how grandparents support children with
      autism and their parents using a family systems perspective. A thematic analysis
      of eighteen semi-structured interviews was conducted with participants from nine
      families, capturing experiences of both parents' and grandparents'. Themes
      identified were family recalibrating; strengthening the family system; and
      current needs and future concerns of grandparents. The views of families
      indicated the overwhelming need to acknowledge the grandparental role in
      supporting families that strengthen the family system by supporting the needs of
      a child with autism. Findings revealed that grandfathers have a calming role in
      these families where children have significant behavioural difficulties.

PMID- 30229358
TI  - Adipose Tissue and Modulation of Hypertension.
AB  - PURPOSE OF REVIEW: Obesity is a major risk factor for the development of
      hypertension (HTN), a leading cause of cardiovascular morbidity and mortality.
      Growing body of research suggests that adipose tissue function is directly
      associated with the pathogenesis of obesity-related HTN. In this review, we will
      discuss recent research on the role of adipose tissue in blood pressure (BP)
      regulation and activation of brown adipose tissue (BAT) as a potentially new
      therapeutic means for obesity-related HTN. RECENT FINDINGS: Adipose tissue
      provides mechanical protection of the blood vessels and plays a role in
      regulation of vascular tone. Exercise and fasting activate BAT and induce
      browning of white adipose tissue (WAT). BAT-secreted FGF21 lowers BP and protects
      against HTN. Browning of perivascular WAT improves HTN. New insights on WAT
      browning and BAT activation can open new avenues of potential therapeutic
      interventions to treat obesity-related HTN.

PMID- 30229361
TI  - Exploring Traits of Autism and Their Impact on Functional Disability in Children
      with Somatic Symptom Disorder.
AB  - Subclinical traits of autism were measured in children with somatic symptom
      disorder (SSD, n = 28) and compared with age-matched controls (n = 26) using the
      Autism Spectrum Quotient (AQ) children's version. The KINDLR quality of life
      questionnaire was used to assess functional disability. Although there was no
      significant group difference in total traits of autism, SSD group had
      significantly greater difficulty in attention switching domain. Logistic
      regression analysis confirmed attention switching and age were associated with
      increased likelihood of SSD. In SSD group, difficulty in attention switching
      significantly negatively correlated with total, family, and friends quality of
      life scores. In conclusion, assessment and treatment targeting difficulties in
      attention switching could be useful when dealing with children with SSD.

PMID- 30229362
TI  - Depression, Anxiety, and Peer Victimization: Bidirectional Relationships and
      Associated Outcomes Transitioning from Childhood to Adolescence.
AB  - Experiences of depression, anxiety, and peer victimization have each been found
      to predict one another, and to predict negative outcomes in the domains of school
      connectedness, social functioning, quality of life, and physical health. However,
      the common co-occurrence of depression, anxiety, and peer victimization
      experiences has made it difficult to disentangle their unique roles in these
      associations. The present study thus sought to characterize the precise nature of
      the bidirectional relationships between depressive symptoms, anxiety, and
      victimization over time, and to examine their unique sequelae during the
      transition from childhood to early adolescence. Longitudinal multi-informant
      (child-reported, parent-reported, and teacher-reported) data from a nationally
      representative sample were analyzed using path analysis when the study child was
      aged 10-11 (n = 4169; Mage = 10.3; 48.8% female) and aged 12-13 (n = 3956; Mage =
      12.4; 48.2% female). Depressive symptoms, anxiety, and peer victimization had
      small but significant unique bidirectional relationships. All three constructs
      also uniquely and prospectively predicted poorer life functioning across all
      domains examined. These results demonstrate that current interventions should
      broaden their scope to simultaneously target depression, anxiety, and peer
      victimization, as each of these experiences independently act as additive risk
      factors for subsequent negative outcomes.

PMID- 30229364
TI  - Regional Supply of Medical Resources and Systemic Overuse of Health Care Among
      Medicare Beneficiaries.
AB  - BACKGROUND: Overuse of health care resources has been identified as the leading
      contributor to waste in the US health care system. OBJECTIVE: To explore health
      care system factors associated with regional variation in systemic overuse of
      health care resources as measured by the Johns Hopkins Overuse Index (JHOI) which
      aggregates systemic overuse of 20 health care services. DESIGN: Using Medicare
      fee-for-service claims data from beneficiaries age 65 or over in 2008, we
      calculated the JHOI for the 306 hospital referral regions in the United States.
      We used ordinary least squares regression and multilevel models to estimate the
      association of JHOI scores and characteristics of regional health care delivery
      systems listed in the Area Health Resource File and Dartmouth Atlas. KEY RESULTS:
      Regions with a higher density of primary care physicians had lower JHOI scores,
      indicating less systemic overuse (P < 0.001). Regional characteristics associated
      with higher JHOI scores, indicating more systemic overuse, included number per
      1000 residents of acute care hospital beds (P = 0.002) and of hospital-based
      anesthesiologists, pathologists, and radiologists (P = 0.02). CONCLUSIONS:
      Regional variations in health care resources including the clinician workforce
      are associated with the intensity of systemic overuse of health care. The role of
      primary care doctors in reducing health care overuse deserves further attention.

PMID- 30229363
TI  - ImFEATbox: a toolbox for extraction and analysis of medical image features.
AB  - PURPOSE: In medical imaging, the digital post-processing and analysis of acquired
      images has become an important research field. Topics include various
      applications of image processing and machine learning aiming to assist
      radiologists in their diagnostic work. A crucial step in successfully
      implementing such systems is finding appropriate mathematical descriptions to
      reflect characteristics of acquired images. Which features are the most
      meaningful ones strongly depends on the underlying scientific/diagnostic question
      and the image itself. This makes researching, implementing and testing features
      time-consuming and cost-intensive. In our work, we aim to address this issue by
      creating ImFEATbox, a publicly available toolbox to extract and analyze image
      features for a wide range of applications. METHODS: To reduce the amount of time
      spent for choosing the right features, we provide an assortment of feature
      extraction algorithms which are suitable for a broad variety of medical image
      processing problems. The toolbox includes both global and local features as well
      as feature descriptors. While being primarily developed in MATLAB, the majority
      of our algorithms is also available in Python to enable access to a wider range
      of researchers. RESULTS: We tested the applicability of ImFEATbox on an FDG
      PET/CT data set of 12 patients diagnosed with lung cancer and an MRI data set of
      50 patients with prostate lesions. Employing the implemented algorithms in an
      exemplary manner, we are able to demonstrate its potential for different
      scientific problems, e.g., show differences between features, indicate
      redundancies in extracted feature sets by means of a correlation analysis and
      training a SVM to distinguish between high-risk and low-risk prostate lesions.
      CONCLUSION: ImFEATbox provides a variety of feature extraction algorithms
      suitable for a large number of post-processing and analysis applications in
      medical imaging. The toolbox is publicly available and can thus be beneficial to
      a wide range of researchers working on medical image analysis.

PMID- 30229365
TI  - [Diabetes mellitus at the interface between pediatric and adult medicine].
AB  - Patients with chronic diseases manifesting in childhood, such as type 1 diabetes,
      need to make an optimal transition from pediatric to adult medical care. This or
      transitionis a challenge for patients and their treatment teams, since metabolic
      control is often unstable at this time of life. Additional factors like the
      social environment, as well as concomitant diseases, also need to be taken into
      account and often represent hurdles to optimal therapy. Transition is an
      important process to guarantee good self-management of diabetes therapy and good
      outcomes in the long term. This review provides an overview and recommendations
      on the topic of transition in diabetes.

PMID- 30229366
TI  - [Cystic fibrosis : A new disease pattern in adult medicine].
AB  - Cystic fibrosis (CF) is an inherited incurable multi-organ disease. Improvement
      in treatment approaches over the last 20 years have led to an increased life
      expectancy where the number of adult patients has doubled and will continue to
      increase exponentially. Due to the use of new substances which modulate the basic
      defect, a substantial improvement in the prognosis can be assumed but the
      existing healthcare structures in Germany do not meet these rising needs. With
      more than 50% of patients being adults, there are only very few internal medicine
      centers available. Only approximately one third of the patients are treated in
      adult health centers. Adolescence in particular is a very vulnerable phase of the
      disease, the risk of comorbidities is increased and adherence to the very
      laborious treatment recommendations is as a rule low. While in many other
      countries transition programs have been evaluated and implemented for more than
      20 years, in Germany there have only been rudimentary approaches to transition.
      Meanwhile investigations are available on the perceptions of adolescents with
      respect to coping with the disease and their treatment needs, including the
      perception of the time when the transition process should begin. Successful
      transition seems to be performed best in combined pediatric and adult centers,
      with the back-up of an experienced multidisciplinary team of healthcare
      providers.

PMID- 30229367
TI  - [Late effects following childhood cancer treatment : A special challenge for
      transition medicine].
AB  - BACKGROUND: Childhood cancer survivors are at risk of cancer- and treatment
      related chronic health conditions. Since these sequelae may occur years after the
      end of treatment, many patients are already adults and have completed pediatric
      oncological care. Thus, successful transition is essential in order to ensure
      long-term surveillance. OBJECTIVES: The present review outlines the most frequent
      late effects of childhood cancer treatment. Moreover, difficulties in transition
      of these patients are discussed and interdisciplinary models of care are
      presented. RESULTS: Late effects following childhood cancer treatment occur in
      over two thirds of patients 30 years after the end of the oncological treatment
      and can affect different organs. The most frequent sequelae are endocrine
      disturbances, cardiac conditions, and subsequent neoplasms. Many late effects are
      effectively manageable if detected early. This necessitates an interdisciplinary
      approach as well as life-long surveillance. CONCLUSIONS: Transition from
      pediatric to internal medicine care as well as a change in the focus of care,
      shifting from relapse centered follow-up to late-effects centered surveillance,
      constitute a special challenge for a successful transition of long-term childhood
      cancer survivors. Specialized late-effects survivorship clinics offering
      interdisciplinary care from pediatric oncologists, specialists of internal
      medicine, and further disciplines enable the early diagnosis and treatment of
      late-effects.

PMID- 30229368
TI  - Distribution and Bioavailability of Trace Metals in Shallow Sediments from Grand
      Lake, Oklahoma.
AB  - The Tri-State Mining District (TSMD) is a historic mining area containing the Tar
      Creek superfund site and is the source for sediment-bound metals in Grand Lake.
      Despite elevated concentrations of cadmium, lead, and zinc, no evidence of
      sediment toxicity has been observed during previous investigations; however,
      these studies were limited to lake transects with mostly deep-water sediments.
      The purpose of this study was to assess whether TSMD-specific sediment toxicity
      thresholds (STTs), developed for small streams and tributaries draining the TSMD,
      are predictive of biological effects within the greater lake body. Investigations
      focused on determining trace metal distribution within the northern reaches of
      Grand Lake, emphasizing shallow water areas (<= 6-m depth), and the effects of
      sediment disturbance on trace metal bioavailability and toxicity to two
      freshwater invertebrates. No significant mortality or differences in growth
      occurred under natural or disturbed sediment conditions for either aquatic
      invertebrate despite using some sediments that exceeded both McDonald general
      sediment quality guidelines (SQGs) and TSMD-specific STTs. Although the simulated
      disturbance event (i.e., vigorously aerating sediments for 30 days before
      toxicity tests) was sufficient to increase trace metal water concentrations and
      detection frequencies, no changes in overall sediment load, bioavailability, or
      toxicity were observed following a 10-day exposure duration. These results
      suggest that TSMD-specific STTs could be used to evaluate Grand Lake sediments
      that could potentially be disturbed by boat traffic, wave action, and dredging
      associated with dock construction as opposed to the more conservative general
      SQGs.

PMID- 30229370
TI  - The effect of anesthetic technique on u-opioid receptor expression and immune
      cell infiltration in breast cancer.
AB  - BACKGROUND: Clinical histological studies demonstrate that the distribution of
      natural killer (NK) cells, other immune cells and MU-opioid receptors (MOR)
      within cancer tissue can predict cancer prognosis. No clinical study has
      evaluated whether anesthetic technique influences immune cell and MOR expression
      within human breast cancer. METHODS: Excised preoperative biopsies and
      intraoperative breast cancer specimens from 20 patients randomly chosen from
      patients previously enrolled in an ongoing, prospective, randomized trial
      (NCT00418457) investigating the effect of anesthetic technique on long-term
      breast cancer outcome were immunohistochemically stained and microscopically
      examined by two independent investigators, masked to randomization, to quantify
      MOR and immune cell infiltration: CD56, CD57 (NK cells), CD4 (T helper cells),
      CD8 (cytotoxic T cells) and CD68 (macrophages). Patients had been randomized to
      receive either a propofol-paravertebral anesthetic with continuing analgesia
      (PPA, n = 10) or balanced general anesthetic with opioid analgesia (GA, n = 10).
      RESULTS: There were no differences between the groups in staining intensity in
      preoperative biopsy specimens. Expression intensity values (median 25-75%) for
      MOR in intraoperative resected biopsy were higher in GA 8.5 (3-17) versus PPA 1
      (0-10), p = 0.04. The numbers of MOR-positive cells were also higher in GA
      patients. Expression and absolute numbers of CD56, CD57, CD4 and CD68 were
      similar in resected tumor in both groups. CONCLUSION: General anesthesia with
      opioid analgesia increased resected tumor MOR expression compared with propofol
      paravertebral anesthetic technique, but the anesthetic technique did not
      significantly influence the expression of immune cell markers.

PMID- 30229369
TI  - Conformational exchange of aromatic side chains by 1H CPMG relaxation dispersion.
AB  - Aromatic side chains are attractive probes of protein dynamics on the millisecond
      time scale, because they are often key residues in enzyme active sites and
      protein binding sites. Further they allow to study specific processes, like
      histidine tautomerization and ring flips. Till now such processes have been
      studied by aromatic 13C CPMG relaxation dispersion experiments. Here we
      investigate the possibility of aromatic 1H CPMG relaxation dispersion experiments
      as a complementary method. Artifact-free dispersions are possible on uniformly 1H
      and 13C labeled samples for histidine delta2 and epsilon1, as well as for
      tryptophan delta1. The method has been validated by measuring fast folding
      unfolding kinetics of the small protein CspB under native conditions. The
      determined rate constants and populations agree well with previous results from
      13C CPMG relaxation dispersion experiments. The CPMG-derived chemical shift
      differences between the folded and unfolded states are in good agreement with
      those obtained directly from the spectra. In contrast, the 1H relaxation
      dispersion profiles in phenylalanine, tyrosine and the six-ring moiety of
      tryptophan, display anomalous behavior caused by 3J 1H-1H couplings and, if
      present, strong 13C-13C couplings. Therefore they require site-selective 1H/2H
      and, in case of strong couplings, 13C/12C labeling. In summary, aromatic 1H CPMG
      relaxation dispersion experiments work on certain positions (His delta2, His
      epsilon1 and Trp delta1) in uniformly labeled samples, while other positions
      require site-selective isotope labeling.

PMID- 30229371
TI  - Differences of physical vs. psychological stress: evidences from glucocorticoid
      receptor expression, hippocampal subfields injury, and behavioral abnormalities.
AB  - The glucocorticoid receptor (GR) is the main effector of the activation of the
      hypothalamus-pituitary-adrenal (HPA) axis, which is caused by different types of
      stress that can be divided into two major categories: physical stress and
      psychological stress. Given the marked presence of GR in the hippocampus, GR
      mediated hippocampal injury might be the core event under stress. The aim of this
      study was to investigate GR expression, hippocampal injury, and behaviors in rats
      to explore the differences between these types of stressors. Adult male rats were
      stressed using a classical model (electrical foot shock and a yoked
      psychologically stressful situation) to induce physical or psychological stress.
      The GR expression, injury of hippocampal subfields and behavioral abnormalities
      were dynamic, as demonstrated using immunofluorescence, 3D magnetic resonance
      imaging (MRI) and open field exploration (OFE), respectively. In addition,
      housing in a normal environment for 6 weeks was used to verify the recovery
      ability of rats. First, GR-mediated hippocampal atrophy and behavioral
      abnormalities were found in the second week under physical stress, but those
      changes did not appear until the fourth week under psychological stress. Second,
      the effects of stress were more pronounced after physical stressors than after
      psychological stressors in the fourth week, but this trend had reversed by the
      sixth week, especially in the DG (Dentate Gyrus) subfield. Except for the rats
      that had experienced 6 weeks of psychological stress, all rats showed significant
      recovery after 6 weeks of housing in a normal environment. The effects of
      physical stress appeared early but were relatively moderate, whereas the effects
      of psychological stress appeared late but were more severe. In addition, GR
      mediated serious injury in the DG might be the cause of the DG volume loss and
      behaviors that could not be reversed.

PMID- 30229372
TI  - Adoption of Liquefied Petroleum Gas Stoves in Guatemala: A Mixed-Methods Study.
AB  - Household air pollution is the sixth leading risk factor for premature mortality
      in Guatemala. Households in Guatemala are gradually adopting liquefied petroleum
      gas (LPG) stoves, but a strong tradition of woodstove use persists. We conducted
      a mixed-methods study of LPG stove use in peri-urban Guatemala. We used
      knowledge, attitudes and practices surveys with 187 LPG stove owners who also
      used woodstoves to identify perceptions of stove and cooking practices. Barriers
      to sustained use of LPG stoves were evaluated through focus groups, participant
      observations with stove users, and key informant interviews with community
      leaders. Seven themes emerged that explain household decisions to use LPG stoves:
      (1) The "new technology" should be framed in terms of what the "old technology"
      lacks, (2) income is not a predictor of gas stove acquisition but may predict
      sustained use, (3) men are key decision-makers but messages about LPG do not
      target them, (4) when stoves are viewed as "prize possessions" they may not be
      used, (5) collective fear about gas stoves is not based on personal experience,
      but on "stories we hear," (6) sustained LPG use is hampered by two major factors,
      seasonally available wood and LPG retailers who are perceived as dishonest, and
      (7) wood fuel collection is a time to enjoy the company of friends and family and
      is not "drudgery." National policies should promote the use of clean cookstove
      technologies in peri-urban and rapidly urbanizing areas in Guatemala where LPG
      stoves are in use, but used intermittently, instead of the current plan to
      install 100,000 "improved" woodstoves by 2032. This could be done by improving
      dependable cylinder distribution services, targeting gas safety and promoting
      positive health messages that appeal to men, as well as women.

PMID- 30229373
TI  - Hematopoietic stem cell and mesenchymal stem cell population size in bone marrow
      samples depends on patient's age and harvesting technique.
AB  - Mesenchymal stem cells (MSCs) are heterogeneous population of cells with great
      potential for regenerative medicine. MSCs are relatively easy to expand in a cell
      culture, however determination of their concentration in harvested tissue is more
      complex and is not implemented as routine procedure. To identify MSCs collected
      from bone marrow we have used two combinations of cell markers (CD45
      /CD73+/CD90+/CD105+ and CD45-/CD271+) and fibroblast colony-forming unit (CFU-F)
      assay. Further, in donors of various ages, mesenchymal stem cell concentration
      was compared with the result of CFU-F assay and with hematopoietic stem cell
      concentration, determined by a standardized flow cytometric assay. A positive
      correlation of MSC populations to the CFU-F numbers is observed, the population
      of the CD45-/CD271+ cells correlates better with CFU-F numbers than the
      population of the CD45-/CD73+/CD90+/CD105+ cells. The relationship between the
      hematopoietic CD45dim/CD34+ cell concentration and mesenchymal CFU-Fs or CD45
      /CD271+ cells shows a positive linear regression. An age-related quantitative
      reduction of hematopoietic CD45dim/CD34+, mesenchymal CD45-/CD73+/CD90+/CD105+
      and CD45-/CD271+ stem cells, and CFU-F numbers were noted. Additionally,
      statistically significant higher CFU-F numbers were observed when bone marrow
      samples were harvested from three different sites from the anterior iliac crest
      instead of harvesting the same sample amount only from one site.

PMID- 30229374
TI  - A QALY loss is a QALY loss is a QALY loss: a note on independence of loss
      aversion from health states.
AB  - Evidence has accumulated documenting loss aversion for monetary and, recently,
      for health outcomes-meaning that, generally, losses carry more weight than
      equally sized gains. In the conventional Quality-Adjusted Life Year (QALY)
      models, which comprise utility for quality and length of life, loss aversion is
      not taken into account. When measuring elements of the QALY model, commonly, the
      (implicit) assumption is that utility for length and quality of life are
      independent. First attempts to quantify loss aversion for QALYs typically
      measured loss aversion in the context of life duration, keeping quality of life
      constant (or vice versa). However, given that QALYs are multi-attribute
      utilities, it may be possible that the degree of loss aversion is dependent on,
      or inseparable from, quality of life and non-constant. We test this assumption
      using non-parametric methodology to quantify loss aversion, under different
      levels of quality of life. We measure utility of life duration for four health
      states within subjects, and present the results of a robustness test of loss
      aversion within the QALY model. We find loss aversion coefficients to be stable
      at the aggregate level, albeit with considerable heterogeneity at the individual
      level. Implications for applied work on prospect theory within health economics
      are discussed.

PMID- 30229375
TI  - Cost-effectiveness of controlling gestational diabetes mellitus: a systematic
      review.
AB  - OBJECTIVE: Timely screening for hyperglycaemia in pregnancy using a simple
      glucose test enhances early detection and control of gestational diabetes
      mellitus (GDM). The aim of this study was to provide an overview of the evidence
      on the cost-effectiveness of identification and/or treatment of GDM. METHODS: We
      conducted a systematic review using three electronic databases (PubMed, EMBASE,
      and Cochrane) of cost-effectiveness studies of GDM screening and treatment
      published during 2000-2017. RESULTS: The initial search discovered 287 references
      (PubMed 86, EMBASE 195, Cochrane library 6) of which six full articles were
      included in the review. Two articles were model-based analysis and the remaining
      four were trial based. Two studies demonstrated favorable cost-effectiveness of
      intensified management of mild GDM. In the other included studies, neither
      screening nor treatment of GDM was shown to be cost effective, although results
      varied with the particular outcome measures used and the assumptions that where
      applied. CONCLUSION: Neither screening nor treating GDM seems to be convincingly
      cost-effective from the studies reviewed. However, all studies were done in high
      income countries with obviously different health systems than low-/middle-income
      countries (LMIC) have. Since detection of GDM may be relatively poor in LMIC,
      screening might be more worthwhile in these countries. Comprehensive research is
      necessary in LMIC, including the potential outcomes of assessing its cost
      effectiveness. Favorable cost-effectiveness could help in bridging the need for
      and access to increased diabetes screening in early pregnancy in these countries.

PMID- 30229376
TI  - Advanced therapy medicinal products and health technology assessment principles
      and practices for value-based and sustainable healthcare.
AB  - BACKGROUND: Advanced therapy medicinal products (ATMPs) are beginning to reach
      European markets, and questions are being asked about their value for patients
      and how healthcare systems should pay for them. OBJECTIVES: To identify and
      discuss potential challenges of ATMPs in view of current health technology
      assessment (HTA) methodology-specifically economic evaluation methods-in Europe
      as it relates to ATMPs, and to suggest potential solutions to these challenges.
      METHODS: An Expert Panel reviewed current HTA principles and practices in
      relation to the specific characteristics of ATMPs. RESULTS: Three key topics were
      identified and prioritised for discussion-uncertainty, discounting, and health
      outcomes and value. The panel discussed that evidence challenges linked to
      increased uncertainty may be mitigated by collection of follow-on data, use of
      value of information analysis, and/or outcomes-based contracts. For discount
      rates, an international, multi-disciplinary forum should be established to
      consider the economic, social and ethical implications of the choice of rate.
      Finally, consideration of the feasibility of assessing the value of ATMPs beyond
      health gain may also be key for decision-making. CONCLUSIONS: ATMPs face a
      challenge in demonstrating their value within current HTA frameworks.
      Consideration of current HTA principles and practices with regards to the
      specific characteristics of ATMPs and continued dialogue will be key to ensuring
      appropriate market access. CLASSIFICATION CODE: I.

PMID- 30229377
TI  - Changes in retinal and choroidal morphology after cerebrospinal fluid pressure
      reduction: a Beijing iCOP study.

PMID- 30229379
TI  - Whole body vibration and treadmill training in Parkinson's disease
      rehabilitation: effects on energy cost and recovery phases.
AB  - BACKGROUND: Although physical treatment is recognized as being beneficial for
      patients with Parkinson's disease (PD), there is scant literature on the type of
      rehabilitation program most useful for patients with PD. The aim of the present
      study was to investigate the effects of two different training protocols (aerobic
      treadmill training, AER and whole body vibration training, WBVT) on energy cost
      and adaptations after exercise and recovery phases, by means of the oxygen
      consumption measurement and the assay of metabolic biochemical substrates.
      METHODS: Twenty male patients with idiopathic Parkinson's disease, aged 51-66
      years, were enrolled. Patients were randomly assigned to the training groups. The
      total work time was 20 min per group for 4 weeks, four times a week. In both
      groups, training intensity was monitored by the ratings of perceived exertion
      (RPE). Workload was gradually increased until patients worked up to the exertion
      level of 13 to 15 on the 20-point Borg scale RPE. The outcome measures were
      oxygen consumption, free fatty acid (FFA), and amino acid (AA) levels. RESULTS:
      The oxygen consumption during exercises does not show significant differences
      between the two training groups. Instead, only in the AER group, excess post
      exercise oxygen consumption measurements increased significantly (p < 0.01) as
      well as FFA availability (p < 0.01). CONCLUSION: The WBVT does not appear to
      require a long time of recovery and leads to less feeling of fatigue, whereas AER
      needs an appropriate recovery time after the training session.

PMID- 30229380
TI  - Suppression of Angiotensin-(1-7) on the Disruption of Blood-Brain Barrier in Rat
      of Brain Glioma.
AB  - Glioblastoma multiforme (GBM) is the most primary brain tumor, specially
      characterized with the damage of blood-brain barrier (BBB). The Ang-(1-7) was
      proven to have an inhibitory effect on glioblastoma growth. However, its role on
      blood-brain barrier (BBB) and the underlying molecular mechanism remains unclear.
      In this study, Ang-(1-7) significantly relieved the damage of blood-brain barrier
      in rats with intracranial U87 gliomas as evaluated by magnetic resonance imaging
      (MRI). Furthermore, its treatment attenuated BBB permeability, tumor growth and
      edema formation. Similarly, Ang-(1-7) also decreased U87 glioma cells barrier
      permeability in vitro. Further analysis showed that Ang-(1-7) could effectively
      restore tight junction protein (claudin-5 and ZO-1) expression levels both in
      rats and U87 glioma cells by affecting the activation of JNK pathway. SP600125,
      an inhibitor of JNK, significantly enhanced the expression of Claudin-5 and ZO-1,
      and decreased the disruption of BBB and enhanced the efficiency of Ang-(1-7) in
      glioma rats. Taken together, this study demonstrated a protective role of Ang-(1
      7) in glioma-induced blood-brain barrier damage by regulating tight junction
      protein expression. Accordingly, Ang-(1-7) may become a promising therapeutic
      agent against glioma.

PMID- 30229381
TI  - Spontaneous Deceleration and Acceleration of Growth Rate in Medullary Thyroid
      Carcinomas Suggested by Changes in Calcitonin Doubling Times Over Long-Term
      Surveillance.
AB  - BACKGROUND: Based on our long-term observation of medullary thyroid carcinoma
      (MTC) patients, we hypothesized that some MTCs have spontaneous deceleration or
      regression of tumor growth over a long term and that a minority may acquire
      growth acceleration. We thus compared the calcitonin doubling time (Ct-DT) in the
      earlier and later half-periods of MTC patients' postoperative course. METHODS: We
      followed 26 MTC patients (14 hereditary and 12 sporadic MTCs) with postoperative
      hypercalcitoninemia with periodic measurements of serum calcitonin (Ct) for >10
      years without major interventions. The median period of Ct measurements was 18.3
      years (range 10.6-30.2 years). We divided the individual patients' study periods
      into the earlier and later halves and calculated the Ct-DTs for both periods.
      RESULTS: In the hereditary group, the Ct-DT in the later half-period (Later-Ct
      DT) was significantly longer than that in the earlier half-period (Earlier-Ct-DT)
      (median 20.0 years vs. 7.1 years, p = 0.013). These values in the sporadic group
      were 20.0 years versus 11.1 years, respectively (p =0.774). Twelve patients
      (seven hereditary and five sporadic) had Later-Ct-DTs significantly longer than
      their Earlier-Ct-DTs (median 27.4 years vs. 4.9 years) and good prognoses. Two
      patients (one hereditary, one sporadic) had Later-Ct-DTs significantly shorter
      than their Earlier-Ct-DTs, and both developed structural recurrence and died of
      the disease. CONCLUSION: Many of the hereditary and some of the sporadic MTC
      patients had elongated Ct-DTs over a long period, suggesting spontaneous
      deceleration and regression of tumor growth. A minority of the MTC patients
      showed Ct-DT shortening, suggesting tumor growth acceleration.

PMID- 30229378
TI  - Will Genetic Engineering Carry Xenotransplantation of Pig Islets to the Clinic?
AB  - PURPOSE OF REVIEW: Porcine islets represent a potentially attractive beta-cell
      source for xenotransplantation into patients with type 1 diabetes, who are not
      eligible to islet allo-transplantation due to a lack of suitable human donor
      organs. Recent progress in genetic engineering/gene editing of donor pigs
      provides new opportunities to overcome rejection of xeno-islets, to improve their
      engraftment and insulin secretion capacity, and to reduce the risk for
      transmission of porcine endogenous retroviruses. This review summarizes the
      current issues and progress in islet xenotransplantation with special emphasis on
      genetically modified/gene edited donor pigs. RECENT FINDINGS: Attempts to
      overcome acute rejection of xeno-islets, especially after intraportal
      transplantation into the liver, include the genetic elimination of specific
      carbohydrate antigens such as alphaGal, Neu5Gc, and Sd(a) for which humans and-in
      part-non-human primates have natural antibodies that bind to these targets
      leading to activation of complement and coagulation. A complementary approach is
      the expression of one or more human complement regulatory proteins (hCD46, hCD55,
      hCD59). Transgenic attempts to overcome cellular rejection of islet
      xenotransplants include the expression of proteins that inhibit co-stimulation of
      T cells. Expression of glucagon-like peptide-1 and M3 muscarinic receptors has
      been shown to increase the insulin secretion of virally transduced porcine islets
      in vitro and it will be interesting to see the effects of these modifications in
      transgenic pigs and islet products derived from them. Genome-wide inactivation of
      porcine endogenous retrovirus (PERV) integrants by mutating their pol genes using
      CRISPR/Cas9 is a recent approach to reduce the risk for PERV transmission by xeno
      islets. Genetic engineering/gene editing of xeno-islet donor pigs facilitated
      major progress towards clinical islet xenotransplantation. The required set of
      genetic modifications will depend on the source of islets (fetal/neonatal vs.
      adult), the mode of delivery (encapsulated vs. free), and the transplantation
      site.

PMID- 30229382
TI  - Postoperative Recovery in Frail, Pre-frail, and Non-frail Elderly Patients
      Following Abdominal Surgery.
AB  - BACKGROUND: The objective of this study is to explore the association between
      frailty and surgical recovery over a 6-month period, in elderly patients
      undergoing elective abdominal surgery. METHODS: A total of 144 patients were
      categorized as frail, pre-frail, and non-frail based on five criteria: weight
      loss, exhaustion, weakness, slowness, and low activity. Recovery to preoperative
      functional status (activities of daily living (ADL) and instrumental activities
      of daily living (IADL)), cognition, quality of life, and mental health was
      assessed at 1, 3, and 6 months postoperatively. A repeated measure logistic
      regression was used to analyze the effect of frailty on recovery over time. The
      effect of frailty on hospitalization outcomes was also evaluated. RESULTS: Mean
      age was 78 +/- 5 years with 17.4% of patients categorized as frail, 60.4% pre
      frail, and 22.2% non-frail. At 6 months, the percent of patients who had
      recovered to preoperative values were: ADL 90%; IADL 76%; cognition 75.5%; mental
      health 66%; and quality of life 70%. While more frail patients experienced
      adverse hospitalization outcomes and fewer had recovered to preoperative
      functional status, these differences were not found to be statistically
      significant. Overall, frailty status was not significantly associated with the
      trajectory of recovery or hospitalization outcomes. CONCLUSION: Strong,
      institutional commitment to quality surgical care, as well as appropriate
      strategies for older patients, may have mitigated the impact of frailty on
      recovery. Further research is needed to examine the role of frailty in the
      surgical recovery process.

PMID- 30229383
TI  - Surgical and Long-Term Survival Outcomes After Laparoscopic and Open Total
      Gastrectomy for Locally Advanced Gastric Cancer: A Propensity Score-Matched
      Analysis.
AB  - BACKGROUND: To compare the surgical and long-term survival outcomes of
      laparoscopic and open total gastrectomy (OTG) for locally advanced gastric cancer
      (AGC). METHODS: We retrospectively evaluated 308 and 900 patients in pathological
      locally AGC who underwent laparoscopic total gastrectomy (LTG) or OTG between
      June 2008 and December 2014. We compared surgical and long-term outcomes between
      the two groups using propensity score matching method. RESULTS: The LTG group
      showed a longer operation time (261.42 vs. 171.00 min, P = 0.001), less blood
      loss (185.47 vs. 217.84 ml, P = 0.000), earlier time to first flatus (3.47 vs.
      4.12 days, P = 0.000), earlier time to start liquid diet (3.76 vs. 4.27 days, P =
      0.000), and shorter postoperative hospital stay (7.56 vs. 8.22 days, P = 0.007).
      The overall complication rate was 15.2% in the LTG group and 17.2% in the OTG (P
      = 0.503). No significant difference was observed in overall survival (OS) and
      disease-free survival (DFS) between LTG and OTG (60.5% vs. 57.1%, P = 0.337;
      57.4% vs. 54.4%, P = 0.341). CONCLUSIONS: Compared to OTG, LTG provides surgical
      benefits and comparable survival outcomes for patients with locally AGC.

PMID- 30229384
TI  - Leptin stimulates the release of pro-inflammatory cytokines in hypothalamic
      astrocyte cultures from adult and aged rats.
AB  - Leptin is an adipose tissue-derived hormone that acts on the hypothalamus in
      order to maintain energy homeostasis. However, leptin can also induce an
      inflammatory response. Increasing evidence has highlighted a critical role of
      astrocytes in the effects of leptin on the hypothalamus. In addition, astrocytes
      participate in neuroinflammation by producing and releasing a wide range of
      inflammatory mediators. In this study, we aimed to investigate the age-dependent
      effect of leptin on pro- and anti-inflammatory cytokines released by the
      hypothalamic astrocyte cultures obtained from newborn, adult, and aged Wistar
      rats. In hypothalamic astrocytes from newborn rats, leptin did not change the
      release of pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha)
      and interleukin 1beta (IL-1beta). On the other contrary, leptin increased the
      release of both TNF-alpha and IL-1beta in astrocyte cultures from adult and aged
      animals. Regarding the anti-inflammatory cytokine interleukin 10 (IL-10), we did
      not observe any change in response to leptin. In conclusion, our data suggests a
      pro-inflammatory action of leptin on the hypothalamus during aging. This in turn
      may be related to the triggering of metabolic disorders, as both of these
      conditions are associated with neuroinflammation.

PMID- 30229385
TI  - Standardized Citrus unshiu peel extract ameliorates dexamethasone-induced
      neurotoxicity and depressive-like behaviors in mice.
AB  - Dried Citrus unshiu peel, also known as Chinpi, have been commonly used as a
      traditional medicine to improve for allergy, inflammation and hepatopathy. Many
      previously studies have reported that citrus flavonoids show neuroprotective
      activities. However, the antidepressant-related effects of C. unshiu peels have
      not been well characterized. Here, the antidepressant-like effects of
      standardized C. unshiu peel extract (SCP) were evaluated in in vivo and in vitro
      depression models induced by dexamethasone (DEX), a synthetic glucocorticoid.
      Male ICR mice (9-week-old) were injected the DEX (40 mg/kg) and were orally given
      SCP daily (30, 100, and 300 mg/kg) for 14 consecutive days. The depressive-like
      behaviors were determined by use of open filed test (OFT), sucrose preference
      test (SPT), tail suspension test (TST), and forced swim test (FST). We show that
      treatment with SCP significantly alleviated DEX-induced depressive-like behaviors
      and reduced neurotoxicity in a concentration dependent manner in SH-SY5Y cells.
      Additionally, repeated DEX injection markedly decreased brain derived
      neurotrophic factor (BDNF) level, tropomyosin receptor kinase B (TrkB), and
      cyclic AMP-response element-binding protein (CREB), while SCP treatment improved
      these levels in the cerebral cortex and hippocampus regions. Our findings suggest
      that SCP exhibits significant antidepressant-like effects in the DEX-induced
      depressive animal model, and this activity may be mediated by preventing
      corticosterone-induced neurotoxicity.

PMID- 30229386
TI  - Carvacrol mitigates proconvulsive effects of lipopolysaccharide, possibly through
      the hippocampal cyclooxygenase-2 inhibition.
AB  - Systemic injection of LPS changes neuronal excitability and increase
      susceptibility for convulsions. Carvacrol exerts neuroprotective and
      antiepileptic effects in animal models. Herein, we investigated the
      anticonvulsive effect of carvacrol on LPS induced seizure severity and possible
      involvement of the hippocampal COX-1 and -2 activities in this effect. Adult male
      wistar rats were used. LPS was injected (400 MUg/kg; i.p.) four hours before the
      PTZ (80 mg/kg; i.p.) injection. Carvacrol was injected (100 mg/kg; i.p.)
      immediately after the LPS injection. Following the PTZ injection, behavioral
      seizures were observed for 30 min. Latency and duration for each stage were
      recorded for analysis. Rats divided into seven groups: (1) PTZ, (2) LPS + PTZ,
      (3) carvacrol + PTZ, (4) LPS + carvacrol + PTZ, (5) LPS, (6) carvacrol, (7)
      intact. At the end of the experimental procedure the hippocampus of all animals
      were extracted to measure COX- 1 and 2 levels using the ELISA. LPS injection four
      hours before the PTZ injection were significantly reduced latency to seizure
      stages 3-5 and increased duration of the stage 5 in compare with PTZ group (p <
      0.05). Carvacrol significantly reduced these effects of LPS on seizure
      susceptibility (p < 0.05). However, injection of carvacrol alone before the PTZ
      injection did not significantly affect seizure indexes in compare with PTZ group.
      Additionally, LPS significantly increased hippocampal level COX-2 but not COX-1
      (p < 0.01) and carvacrol significantly attenuates this effect of LPS (p < 0.001).
      Carvacrol prevents the proconvulsant effect of LPS possibly through the
      inhibition of the COX-2 increased activity.

PMID- 30229388
TI  - Depressive Symptoms Before and After Antiretroviral Therapy Initiation Among
      Older-Aged Individuals in Rural Uganda.
AB  - This study aims to characterize associations between depression symptom severity
      and HIV infection, both prior to and in years after ART initiation, among older
      adults. The Ugandan Non-Communicable Diseases & Aging Cohort Study (UGANDAC) is a
      study of 154 PLWH on ART and 142 community-based, HIV-negative controls. The
      Hopkins Checklist (HSCL), a 15-item depression scale, was used to screen for
      depression. We estimate differences in depressive symptoms by HIV and ART status
      and use multivariable log binomial regression to quantify differences in probable
      depression between PLWH on ART. HIV-infected and HIV-uninfected participants had
      a similar age (mean 52.0 vs. 51.9, p = 0.854) and sex distribution (47.4 vs.
      47.9% female, p = 0.934). PLWH on ART had lower depression symptom severity than
      HIV-uninfected controls (mean score: 1.50 vs. 1.60, p = 0.006) and a lower
      prevalence of probable depression (21.4 vs. 33.8%, p = 0.017). Among 102 PLWH
      with pre-ART depression screening scores available, their mean depression symptom
      severity was similar to HIV-uninfected participants (mean 1.56 vs. 1.60, p =
      0.512). In adjusted models, PLWH on ART had a lower prevalence of probable
      depression than HIV-negative controls [adjusted prevalence ratio: 0.68 (95% CI
      0.47-0.99)]. In an observational cohort of PLWH over 40 on long-term ART and
      matched, community-based HIV-uninfected controls in rural Uganda, we found a
      lower prevalence of self-reported depression among aging PLWH on ART.

PMID- 30229389
TI  - [Conventional and electroanatomical mapping-a pivotal diagnostic tool to provide
      a basis for ablative therapy of complex atrial and ventricular arrhythmias].

PMID- 30229387
TI  - Novel Concepts in Psoriatic Arthritis Management: Can We Treat to Target?
AB  - PURPOSE OF REVIEW: Psoriatic arthritis (PsA) is a chronic inflammatory
      spondyloarthritis that can cause progressive joint damage and irreversible
      disability. Advances in modern therapies, now mean a target of remission is an
      achievable goal in PsA. There is strong and consistent evidence that a treat-to
      target (T2T) approach to PsA management results in better patient outcomes;
      however, the practicalities of incorporating this strategy into routine clinical
      practice remain a challenge. The heterogeneous nature of this condition and the
      need for validated outcome measures have to-date hampered consensus on a
      definition of remission. This review aims to summarise the current T2T research
      landscape in PsA and highlight potential roles for biomarkers and imaging
      advances in revolutionising the T2T concept. RECENT FINDINGS: There is a growing
      body of evidence to support the implementation of a T2T strategy, using a pre
      defined target in PsA management, with significant benefits in disease outcome,
      physical function and quality of life. Whilst remission is the ultimately goal
      for PsA patients and their clinicians, further comparative studies of different
      treatment targets are needed to establish a widely acceptable definition of
      remission.

PMID- 30229390
TI  - Mapping of complex arrhythmias: where do we stand and where do we go from here?

PMID- 30229391
TI  - Effect of PET/CT standardized uptake values on complete response to treatment
      before definitive chemoradiotherapy in stage III non-small cell lung cancer.
AB  - PURPOSE: The standard treatment for patients with stage III non-small cell lung
      cancer (NSCLC), unsuitable for resection and with good performance, is definitive
      radiotherapy with cisplatin-based chemotherapy. Our aim is to evaluate the effect
      of the maximum value of standardized uptake values (SUVmax) of the primary tumor
      in positron emission tomography-computed tomography (PET/CT) before treatment on
      complete response (CR) and overall survival. METHODS: The data of 73 stage III
      NSCLC patients treated with concurrent definitive chemoradiotherapy (CRT) between
      2008 and 2017 and had PET/CT staging in the pretreatment period were evaluated.
      ROC curve analysis was performed to determine the ideal cut-off value of
      pretreatment SUVmax to predict CR. RESULTS: Median age was 58 years (range 27-83
      years) and 66 patients were male (90.4%). Median follow-up time was 18 months
      (range 3-98 months); median survival was 23 months. 1-year overall survival (OS)
      rate and 5-year OS rate were 72 and 19%, respectively. Median progression-free
      survival (PFS) was 9 months; 1-year PFS rate and 5-year PFS rate were 38 and 19%,
      respectively. The ideal cut-off value of pretreatment SUVmax that predicted the
      complete response of CRT was 12 in the ROC analysis [AUC 0.699 (0.550-0.833)/P <
      0.01] with a sensitivity of 83%, and specificity of 55%. In patients with SUVmax
      < 12, CR rate was 60%, while, in patients with SUV >= 12, it was only 19% (P =
      0.002). Median OS was 26 months in patients with pretreatment SUVmax < 12, and 21
      months in patients with SUVmax >= 12 (HR = 2.93; 95% CI 17.24-28.75; P = 0.087).
      CR rate of the whole patient population was 26%, and it was the only factor that
      showed a significant benefit on survival in both univariate and multivariate
      analyses. CONCLUSION: Pretreatment SUVmax of the primary tumor in PET/CT may
      predict CR in stage III NSCLC patients who were treated with definitive CRT.
      Having clinical CR is the only positive predictive factor for prolonged survival.

PMID- 30229392
TI  - Effect of Paclitaxel-based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on
      colonic anastomosis in a rat model.
AB  - BACKGROUND: Paclitaxel has been used frequently for Hyperthermic Intraperitoneal
      Chemotherapy (HIPEC) for ovarian carcinomatosis. Cytoreductive surgery and HIPEC
      are associated with high rates of morbidity being anastomotic dehiscence one of
      the most frequent. The objective of this study is to quantify the effect of
      Paclitaxel-based HIPEC on colonic anastomosis in an experimental rat model.
      METHODS: After left colon resection and anastomosis, animals were randomized into
      four groups: Controls (C); Hyperthermia (H); Normothermic Intraperitoneal
      Paclitaxel (CP) and Paclitaxel-based HIPEC (HP). On postoperative day four,
      animals' peritoneal cavities were examined macroscopically, colon anastomosis
      burst pressures measured and specimens analyzed histologically. RESULTS: Thirty
      nine animals were randomized and 36 were included in the analysis. H group
      presented the highest burst pressure 105.11 +/- 22.9 mmHg, which was 27% higher
      than C (77.89 +/- 27.6 mmHg). On the other hand, HP presented the lowest burst
      pressure 64 +/- 26 mmHg, 16% lower than C group and 39% lower than H, being this
      latter difference statistically significant (p = 0.004). There were no
      significant differences regarding weight loss, adhesion scores, perianastomotic
      abscesses and histological findings (inflammation, fibroblasts, neoangiogenesis,
      and collagen among groups). CONCLUSION: Strength of colonic anastomosis was
      improved by isolated hyperthermia and negatively affected by Paclitaxel-based
      HIPEC.

PMID- 30229393
TI  - S100B promotes microglia M1 polarization and migration to aggravate cerebral
      ischemia.
AB  - AIM AND OBJECTIVE: S100B has been found abundantly expressed in microglia during
      cerebral ischemia. However, S100B effects on phenotype changes and migration of
      microglia are unclear. METHODS: Real-time PCR of S100B, M1 and M2 markers were
      tested to characterize phenotypic changes in microglia in mice middle cerebral
      artery occlusion (MCAO) model. Migration assay and additional mechanism studies
      were performed to elucidate the role of NF-kappaB in S100B-mediated microglia
      M1/M2 phenotype change and migration. Finally, S100B treatment on MCAO models was
      performed to show the in vivo evidence. RESULTS: S100B was identified as an
      induced gene with its pattern in accordance with M1 markers in mice MCAO model.
      That S100B was promoted by M1 stimuli whereas inhibited by M2 stimuli further
      confirmed S100B a M1 marker. Moreover, S100B promotes microglia M1 polarization
      with enhanced migration ability and inhibits M2 polarization. Additionally, NF
      kappaB is essential in S100B control in microglia M1/M2 polarization and
      migration. Furthermore, S100B aggravated cerebral ischemia in murine MCAO model
      and exacerbated the microglia M1 polarization and migration. CONCLUSIONS: Our
      findings demonstrate that S100B promotes microglia M1 polarization to aggravate
      cerebral ischemia, and provide a better understanding on the therapeutic effects
      of S100B and/or its antagonist/neutralization antibody in stroke.

PMID- 30229394
TI  - Aptamer-Modified Magnetic Nanosensitizer for In Vivo MR Imaging of HER2
      Expressing Cancer.
AB  - The aim of this study was the development of a human epidermal growth factor
      receptor 2 (HER2)-targetable contrast agent for magnetic resonance imaging (MRI)
      with a high magnetic sensitivity. An anti-HER2 aptamer-modified magnetic
      nanosensitizer (AptHER2-MNS) was prepared by conjugation with 5'-thiol-modified
      aptamers and maleimidylated magnetic nanocrystals (MNCs). The physicochemical
      characteristics and targeting ability of AptHER2-MNS were confirmed, and the
      binding affinity (Kd) onto HER2 protein of AptHER2-MNS was 0.57 +/- 0.26 nM. In
      vivo MRI contrast enhancement ability was also verified at HER2+ cancer cell
      (NIH3T6.7)-xenograft mouse models (n = 3) at 3T clinical MRI instrument. The
      control experiment was carried out using non-labeled MNCs. The results indicated
      that up to 150% contrast enhancement was achieved at the tumor region in the T2
      weighted MR images after the injection of the AptHER2-MNS agent in mice that
      received the NIH3T6.7 cells.

PMID- 30229396
TI  - Exploring non-linear distance metrics in the structure-activity space: QSAR
      models for human estrogen receptor.
AB  - BACKGROUND: Quantitative structure-activity relationship (QSAR) models are
      important tools used in discovering new drug candidates and identifying
      potentially harmful environmental chemicals. These models often face two
      fundamental challenges: limited amount of available biological activity data and
      noise or uncertainty in the activity data themselves. To address these
      challenges, we introduce and explore a QSAR model based on custom distance
      metrics in the structure-activity space. METHODS: The model is built on top of
      the k-nearest neighbor model, incorporating non-linearity not only in the
      chemical structure space, but also in the biological activity space. The model is
      tuned and evaluated using activity data for human estrogen receptor from the US
      EPA ToxCast and Tox21 databases. RESULTS: The model closely trails the CERAPP
      consensus model (built on top of 48 individual human estrogen receptor activity
      models) in agonist activity predictions and consistently outperforms the CERAPP
      consensus model in antagonist activity predictions. DISCUSSION: We suggest that
      incorporating non-linear distance metrics may significantly improve QSAR model
      performance when the available biological activity data are limited.

PMID- 30229395
TI  - Acute Treatment of Stroke (Except Thrombectomy).
AB  - PURPOSE OF REVIEW: The management of patients with acute stroke has been
      revolutionized in recent years with the advent of new effective treatments. In
      this rapidly evolving field, we provide an update on the management of acute
      stroke excluding thrombectomy, looking to recent, ongoing, and future trials.
      RECENT FINDINGS: Large definitive trials have provided insight into acute stroke
      care including broadening the therapeutic window for thrombolysis, alternatives
      to standard dose alteplase, the use of dual antiplatelet therapy early after
      minor ischemic stroke, and treating elevated blood pressure in intracerebral
      hemorrhage. Further ongoing and future trials are eagerly awaited in this ever
      expanding area. Although definitive trials have led to improvements in acute
      stroke care, there remains a need for further research to improve our
      understanding of pathophysiological mechanisms underlying different stroke types
      with the potential for treatments to be tailored to the individual.

PMID- 30229397
TI  - ATP mediates a negative autocrine signal on stimulus-secretion coupling in mouse
      pancreatic beta-cells.
AB  - PURPOSE: The role of ATP, which is secreted by pancreatic beta-cells, is still a
      matter of debate. It has been postulated that extracellular ATP acts as a
      positive auto- or paracrine signal in beta-cells amplifying insulin secretion.
      However, there is rising evidence that extracellular ATP may also mediate a
      negative signal. METHODS: We evaluated whether extracellular ATP interferes with
      the Ca2+-mediated negative feedback mechanism that regulates oscillatory activity
      of beta-cells. RESULTS: To experimentally uncover the Ca2+-induced feedback we
      applied a high extracellular Ca2+ concentration. Under this condition ATP (100
      uM) inhibited glucose-evoked oscillations of electrical activity and
      hyperpolarized the membrane potential. Furthermore, ATP acutely increased the
      interburst phase of Ca2+ oscillations and reduced the current through L-type Ca2+
      channels. Accordingly, ATP (500 uM) decreased glucose-induced insulin secretion.
      The ATP effect was not mimicked by AMP, ADP, or adenosine. The use of specific
      agonists and antagonists and mice deficient of large conductance Ca2+-dependent
      K+ channels revealed that P2X, but not P2Y receptors, and Ca2+-dependent K+
      channels are involved in the underlying signaling cascade induced by ATP. The
      effectiveness of ATP to interfere with parameters of stimulus-secretion coupling
      is markedly reduced at low extracellular Ca2+ concentration. CONCLUSION: It is
      suggested that extracellular ATP which is co-secreted with insulin in a pulsatile
      manner during glucose-stimulated exocytosis provides a negative feedback signal
      driving beta-cell oscillations in co-operation with Ca2+ and other signals.

PMID- 30229398
TI  - Longitudinal Pharmacokinetics of Mycophenolic Acid in Elderly Renal Transplant
      Recipients Compared to a Younger Control Group: Data from the nEverOld Trial.
AB  - BACKGROUND AND OBJECTIVES: Elderly patients are increasingly likely to be
      recipients of transplants. However, the pharmacokinetics of mycophenolic acid
      (MPA) in this population are yet to be studied in detail. The objective of this
      study was to assess whether there were differences in MPA pharmacokinetic
      parameter values between elderly recipients and younger-adult recipients during
      the 6 months immediately following renal transplantation. METHODS: In this
      analysis, the longitudinal 12-h pharmacokinetics of MPA, administered as enteric
      coated mycophenolate sodium (EC-MPS), were evaluated in 44 elderly renal
      transplant recipients and compared with the corresponding pharmacokinetics of MPA
      in 31 younger adult recipients. Measurements were performed at 7, 30, 60, 90, and
      180 days post-transplantation. All patients received tacrolimus and prednisone.
      RESULTS: The elderly patients were 30 years older than the younger controls, with
      a predominance of males and Caucasians. Elderly patients had lower serum albumin
      than the younger controls during the first 6 months after transplantation. The
      mean estimated total body MPA clearance of the elderly recipients was not
      significantly different from that of the controls at any analyzed time point (the
      mean clearance across all time points was 0.31 +/- 0.17 vs 0.30 +/- 0.25 L/h/kg).
      MPA exposure, as evaluated from the area under the 12-h time versus measured MPA
      concentration (adjusted for dose/body weight) curve, did not differ between the
      groups at any time point (mean exposure across all time points was 4.68 +/- 3.61
      vs 5.95 +/- 4.29 ug.h/mL per mg/kg for the elderly recipients and the controls).
      CONCLUSIONS: These data show that the pharmacokinetics of MPA in elderly renal
      transplant recipients were no different to those of younger-adult recipients in
      this study population. CLINICALTRIALS.GOV: NCT 01631058.

PMID- 30229399
TI  - DNMT1, a Novel Regulator Mediating mTORC1/mTORC2 Pathway-Induced NGF Expression
      in Schwann Cells.
AB  - Schwann cells play an important role in maintaining the normal function of
      peripheral nerves via the secretion of nerve growth factor (NGF). The mTOR
      signaling pathway is known as a kind of Ser/Thr protein kinase that regulates
      various cell functions. DNA methyltransferase 1 (DNMT1) is an epigenetic
      regulator and downstream target of the mTOR pathway. In the present study, we
      explored the relationship between NGF expression and the mTOR pathway/DNMT1 in
      RSC96 cells. The results showed that both rapamycin and Torin 1 downregulated NGF
      expression via the inhibition of phospho-mTOR (Ser 2448) and phospho-S6K1 (Thr
      389). Similarly, the silencing of RAPTOR and RICTOR decreased NGF expression by
      56.7% and 52.4%, respectively, in RSC96 cells compared with the control siRNA
      treatment, which was accompanied by reduced phospho-S6K1 (Thr 389). The mTOR/S6K1
      activator MHY1485 increased NGF expression by 28.7% and 17.1% 1 day and 2 day
      after stimulation, respectively, compared to the corresponding control group in
      RSC96 cells. Furthermore, DNMT1 was enhanced by 94.5% and 42.5% with mTOR pathway
      inhibitor (rapamycin and Torin 1, respectively) treatment for 3 day compared with
      the control group. Additionally, the inhibition of DNMT1 with a chemical
      inhibitor or a specific shRNA plasmid upregulated NGF in RSC96 cells. In summary,
      our findings suggest that DNMT1 is the downstream target of the mTOR pathway and
      mediates the mTOR pathway inhibition-induced reduction in NGF expression in
      Schwann cells. Activation of the mTOR signaling pathway and/or inhibition of
      DNMT1 increased NGF expression, which may benefit patients suffering from NGF
      deficiencies, such as diabetic peripheral neuropathy.

PMID- 30229400
TI  - Deciphering the Role of EGL-3 for Neuropeptides Processing in Caenorhabditis
      elegans Using High-Resolution Quadrupole-Orbitrap Mass Spectrometry.
AB  - Neuropeptides are derived from large and inactive proteins which require
      endoproteolytic processing for the biosynthesis of the bioactive peptides. The
      maturation of pro-neuropeptide to neuropeptide is believed to be performed by
      ortholog pro-protein convertase EGL-3 in Caenorhabditis elegans (C. elegans).
      Furthermore, ortholog of Cathepsin L, CPL-1 are found in C. elegans and can
      potentially cleave paired basic amino acids at the N-terminal suggesting the
      presence of both pathways. The objective of this study was to decipher the role
      of EGL-3 in the proteolysis of FMRF amide-related peptides (FLPs) or neuropeptide
      like proteins (NLPs) using synthetic surrogate peptides based on a universal
      enzymatic cleavage pattern published by Schechter and Berger and used widely in
      enzymology. The results show evidence that proteolysis controls FLP-21 and NLP-8
      related neuropeptide levels in C. elegans. Surrogate peptides were degraded
      rapidly when exposed to C. elegans S9 fractions leading to the formation of
      specific peptide fragments related to EGL-3 and CPL-1 pathway. The results
      suggest that CPL-1 pathway does not compensate for the loss of the EGL-3 pathway.
      Proteolysis of pro-neuropeptides associated to FLP-21 and NLP-8 in elg-3 mutants
      are severely hampered leading to a lack of mature bioactive neuropeptides.

PMID- 30229401
TI  - Lung cancer screening: an emerging cancer control issue presents opportunities
      for an awareness campaign in rural Michigan.
AB  - Lung cancer is the leading cause of cancer deaths in the United States
      representing about 25% of all cancer deaths. The risk from smoking has increased
      over time with racial/ethnic minorities and disadvantaged populations having
      higher smoking rates and experiencing greater burden of lung cancer compared to
      other populations. Rural populations, in particular, experience higher rates of
      tobacco usage associated with increased incidence of lung cancer. National
      efforts to identify lung cancer in its early stage would greatly benefit high
      risk populations, consequently reducing advanced cancers and potentially
      decreasing smoking rates. In 2013, lung cancer screening with low-dose computed
      tomography was recommended by the US Preventive Services Task Force for early
      detection of lung cancer. These guidelines were developed after the results of
      the National Lung Screening Trial. The National Lung Screening Trial study showed
      a 20% reduction in deaths of participants who were current or former heavy
      smokers who were screened with low-dose computed tomography versus those screened
      by chest X-ray. In response to this evidence and using state lung cancer burden
      data and local smoking rates as a guide, Michigan implemented a lung cancer
      screening awareness campaign in the rural northern, lower peninsula. Awareness of
      lung cancer screening was increased through the use of a variety of media
      including gas station/convenience store small media, digital media, radio
      broadcast media, and the use and marketing of a website that provided lung cancer
      screening information and resources.

PMID- 30229402
TI  - Increasing Awareness of Uterine Cancer Risks and Symptoms by Using Campaign
      Materials from Inside Knowledge: Get the Facts About Gynecologic Cancer.
AB  - Uterine cancer is the fourth most commonly diagnosed cancer among women in the
      USA. To increase knowledge among women and healthcare providers about uterine
      cancer, the Centers for Disease Control and Prevention's National Comprehensive
      Cancer Control Program (NCCCP) partnered with the Inside Knowledge: Get The Facts
      About Gynecologic Cancer campaign to present facilitated discussions about
      uterine cancer with women and providers. After standardized training, local NCCCP
      grantees developed and led community-based, tailored, facilitated discussions for
      public participants and providers. Pre- and post-session surveys were
      administered to assess knowledge of risk factors, symptoms, testing, and
      diagnostic options for uterine cancer. Following the facilitated sessions,
      significantly, more public respondents identified uterine cancer risk factors
      (e.g., advanced age, post-menopausal status). However, they also equally
      identified factors not associated with uterine cancer (e.g., smoking, HPV). Non
      OB/GYN provider knowledge increased, significantly for some risks and symptoms,
      and their confidence with relaying uterine cancer information to patients
      significantly increased from 51.4 to 91.0% (P < 0.0001). Relatively low
      proportions of OB/GYNs (19.3%), other primary care providers (46.2%), and public
      participants (51.8%) knew post-session that genetic testing for Lynch syndrome
      can help stratify women for uterine cancer risk. Participant knowledge
      significantly increased for some risk factors and symptoms following Inside
      Knowledge educational sessions; however, some knowledge gaps remained. Overall,
      the Inside Knowledge materials are effective for increasing uterine cancer
      awareness among providers and women. Additional provider education could include
      specific resources related to uterine cancer genetic associations, as
      advancements in genetic testing for all uterine cancers are currently being made.

PMID- 30229403
TI  - Surgical outcome in smaller symptomatic vestibular schwannomas. Is there a role
      for surgery?
AB  - BACKGROUND: Currently, there is no consensus in the initial management of small
      vestibular schwannomas (VSs). They are routinely watched and/or referred for
      radiosurgical treatment, although surgical removal is also an option. We hereby
      evaluate clinical outcomes of patients who have undergone surgical removal of
      smaller symptomatic VSs. METHODS: Patients with vestibular schwannomas (grade T1
      T3b according to Hannover classification) were reviewed. Patients with
      symptomatic tumors who underwent surgery were evaluated. Their preoperative
      hearing status was based on the guideline of the committee on hearing and
      equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery (AAO
      HNS) foundation. Their postoperative facial nerve function, hearing status,
      vestibular symptoms, and degree of tumor resection were assessed. RESULTS: Thirty
      patients were selected for surgery via a retrosigmoid approach based on their
      age, symptoms, and their own decision-making after discussion of management
      options. Most patients presented with hearing loss. Seventeen patients had useful
      hearing preoperatively. Among them, 10 patients (59%) preserved useful hearing
      (class A or B) postoperatively. MRI at 1-year follow-up confirmed complete
      resection in 26/29 patients. Also, 29 patients (97%) had HB grade I-II, and 1
      patient had HB III at 1-year follow-up. Except for 1 patient with CSF leak, 1
      patient with delayed facial nerve palsy, and 2 patients with asymptomatic sigmoid
      sinus occlusion, there were no other new morbidities. CONCLUSION: Although both
      observation and radiosurgery are valid options in the management of smaller size
      vestibular schwannomas, surgical treatment seems to offer a high rate of facial
      nerve preservation, a reasonable rate of hearing sparing, and a high total
      resection rate. Clinicians should consider surgical treatment as a valid option
      in the initial management of symptomatic small vestibular schwannomas in younger
      patients.

PMID- 30229405
TI  - Single and dual coil shock efficacy and predictors of shock failure in patients
      with modern implantable cardioverter defibrillators-a single-center paired
      randomized study.
AB  - PURPOSE: Implantable cardioverter defibrillators (ICDs) can treat life
      threatening tachyarrhythmia with high-voltage shocks. The aims were to compare
      the efficacy of single and dual coil shock vectors in modern ICDs and to identify
      predictors of shock failure. METHODS: This is a single-center paired randomized
      study including 216 patients with mixed indications and ICDs from four
      manufacturers. All patients underwent two implant defibrillation tests using
      single and dual coil vectors with the test order randomized. Tested shock energy
      differed slightly between manufacturers because of differences in device
      programmability: first shock approximately 15 J below maximal output-if failed,
      second shock approximately 10 J below maximal output-if failed, third shock at
      maximal output. RESULTS: First shock success rate was 399/432 (92.4%). Comparing
      single and dual coil vectors, no differences were seen in first shock efficacy
      (91.7% vs. 93.1%, P = 0.629) or lowest tested succesfully stored energy (27.2 J
      vs. 27.1 J, P = 0.620). All successive internal shocks failed in 4/432 (0.9%) of
      inductions requiring external rescue shocks to restore circulation. Multivariate
      predictors of first shock failure were QRS duration (relative risk 0.81 per 10
      ms, P = 0.001), amiodarone treatment (relative risk 3.30, P = 0.003), and body
      height (relative risk 1.70 per 10 cm, P = 0.019). CONCLUSIONS: Implant
      defibrillation testing of modern intravenous ICD systems demonstrates high shock
      efficacy with no difference between single and dual coil vectors.

PMID- 30229404
TI  - Three dimensional neuro-retinal rim thickness and retinal nerve fiber layer
      thickness using high-definition optical coherence tomography for open-angle
      glaucoma.
AB  - PURPOSE: To compare the diagnostic capability of three-dimensional (3D) neuro
      retinal rim thickness (NRR) with existing optic nerve head and retinal nerve
      fiber layer (RNFL) scan parameters using high-definition optical coherence
      tomography (HD-OCT). DESIGN: Retrospective study. METHODS: Based on the mean
      deviation (MD) of the Humphrey Field Analyzer (HFA), the 152 subjects were
      categorized into mild (MD > - 6 dB, 100), moderate (MD - 6 to - 12 dB, 26), and
      severe (MD < - 12 dB, 26) glaucoma. The HD-OCT values of NRR, RNFL and ganglion
      cell inner plexiform layer (GCIPL) thicknesses, along with those of other
      parameters (rim area, disc area) were obtained, and the average NRR thickness was
      calculated. RESULTS: For all of the HD-OCT parameters, RNFL thickness showed a
      higher area under the ROC (AUROC) curve (range: 0.937-1.000) than did NRR
      thickness (range: 0.827-1.000). There were significant RNFL, NRR, and GCIPL AUROC
      curve differences among the mild, moderate and severe glaucoma groups. RNFL
      thickness for mild glaucoma showed a significantly larger area than did NRR
      thickness [area difference: 0.110 (+/- 0.025); p value < 0.0001). Furthermore,
      RNFL relative to NRR thickness yielded higher sensitivity (85-100% vs. 72-100%)
      and specificity (89-100% vs. 84-100%) for diagnosis of glaucoma. CONCLUSION: RNFL
      thickness remains significantly better than 3D NRR thickness in terms of glaucoma
      diagnostic capability in HD-OCT.

PMID- 30229406
TI  - Catheter ablation of atrial fibrillation with nonfluoroscopic catheter
      visualization-a prospective randomized comparison.
AB  - PURPOSE: The application of a novel platform for nonfluoroscopic catheter sensor
      tracking within pre-recorded x-ray loops in the context of catheter ablation of
      atrial fibrillation (AF) demonstrated significant potential for reduction of
      fluoroscopy. We sought to provide the first prospective randomized comparison of
      fluoroscopy needs, procedure times, and complications in AF catheter ablation
      with or without additional use of nonfluoroscopic catheter visualization (NFCV).
      METHODS: Patients with AF were randomized into two groups before scheduled
      radiofrequency ablation: (1) using established mapping systems and fluoroscopy as
      needed (CONV group) or (2) with additional NFCV (NFCV group). All procedures were
      performed in the same lab using the same ablation catheter tip technology and the
      same mapping and ablation strategies. Primary endpoints were radiation time and
      dose. Secondary endpoints were procedural parameters, complications, and long
      term success. RESULTS: A total of 80 patients (48 male patients, mean age 60
      years, 46 patients with paroxysmal AF) were randomized into the two groups.
      Clinical parameters between both groups were similar. NFCV use reduced mean
      fluoroscopy time (1.9 vs. 13.2 min, p < 0.001) and mean dose (510 vs. 1549 Gycm2,
      p < 0.001) significantly. Procedural parameters were similar in the two groups.
      One conservatively treated groin complication occurred (1.3%). CONCLUSIONS:
      Radiation exposure can be significantly reduced by using the novel NFCV
      technology in addition to standard AF ablation technologies without negative
      effects on procedure durations, success rates, or complication rates. With the
      use of the technology, abandonment of lead protection for EP staff is possible
      following transseptal puncture.

PMID- 30229407
TI  - Telomere and its role in the aging pathways: telomere shortening, cell senescence
      and mitochondria dysfunction.
AB  - Aging is a biological process characterized by a progressive functional decline
      in tissues and organs, which eventually leads to mortality. Telomeres, the
      repetitive DNA repeat sequences at the end of linear eukaryotic chromosomes
      protecting chromosome ends from degradation and illegitimate recombination, play
      a crucial role in cell fate and aging. Due to the mechanism of replication,
      telomeres shorten as cells proliferate, which consequently contributes to
      cellular senescence and mitochondrial dysfunction. Cells are the basic unit of
      organismal structure and function, and mitochondria are the powerhouse and
      metabolic center of cells. Therefore, cellular senescence and mitochondrial
      dysfunction would result in tissue or organ degeneration and dysfunction followed
      by somatic aging through multiple pathways. In this review, we summarized the
      main mechanisms of cellular senescence, mitochondrial malfunction and aging
      triggered by telomere attrition. Understanding the molecular mechanisms involved
      in the aging process may elicit new strategies for improving health and extending
      lifespan.

PMID- 30229408
TI  - Temperature inversion and air pollution relationship, and its effects on human
      health in Hanoi City, Vietnam.
AB  - This study aimed to investigate the effects of temperature inversions on the
      concentration of some pollutants in the atmosphere in Hanoi City, Vietnam, during
      the period from 2011 to 2015. This work also aimed to evaluate relationships
      between the thermal inversion and health effects that are associated with air
      pollution. During this period, the temperature inversions were most frequently
      presenting from November to March in Hanoi City. Air quality data was gathered
      from air quality monitoring stations located in the study area. The data showed
      that levels of NO2, SO2, PM10 and PM2.5 increased when the inversions
      strengthened. Cases of two types of diseases (acute respiratory diseases and
      cardiovascular diseases), which are linked to atmospheric air pollution, were
      considered on number of patients under 15 and above 60 years old at National
      Geriatric Hospital and National Otorhinolaryngology Hospital. There was
      significant increase in the daily average number of hospital visits with
      increasing surface-based inversions. The statistical analysis showed that the
      temperature inversions correlated with concentration of air pollutants and the
      number of patients in 5 years.

PMID- 30229409
TI  - Exploring the paths between self-compassionate attributes and actions, body
      compassion and disordered eating.
AB  - The relationship between self-compassion and well-being and health (e.g. a lower
      proneness for eating-related disturbances) is well stressed in the literature.
      However, the specific contribution of self-compassionate attributes, actions, and
      body compassion remains scarcely studied. The main aim of the present study was
      to examine whether the link between self-compassionate attributes and disordered
      eating attitudes and behaviours is mediated by self-compassionate actions and
      body compassion, in a sample of 299 Portuguese women from the general population.
      The tested model explained 44% of eating psychopathology's variance and presented
      excellent fit indices. The most interesting contribution of this study was the
      suggestion that the ability to act in accordance with self-compassionate
      attributes is associated with higher levels of body compassion, that is, an
      attitude of appreciation, acceptance, warmth toward body-related thoughts,
      perceptions and feelings, which reflects in a lower susceptibility to adopt
      disordered eating attitudes and behaviours. These results seem to offer an
      important contribution for research and clinical practice by supporting the
      importance of including strategies to develop self-compassionate skills and body
      compassion competencies in prevention and treatment programs in the area of
      eating psychopathology. Level of evidence Level III, evidence obtained from a
      well-designed cohort.

PMID- 30229410
TI  - Interrelationship in the prognostic efficacy of regional coronary flow reserve,
      fractional flow reserve, high-sensitivity cardiac troponin-I and NT-proBNP in
      patients with stable coronary artery disease.
AB  - This study aimed to investigate the combined efficacy in prediction of major
      adverse cardiac events (MACE) by coronary regional physiological indices
      including coronary flow reserve (CFR) or fractional flow reserve (FFR) and high
      sensitivity cardiac troponin-I (hs-cTnI) or N-terminal pro brain natriuretic
      peptide (NT-proBNP). Impaired CFR, decreased FFR, elevated cardiac troponin, and
      NT-proBNP are all associated with increased MACE, while these interaction or
      collinearity remains uncertain. The study included 429 patients with stable
      coronary artery disease (CAD) evaluated hs-cTnI and NT-proBNP levels before
      regional physiological measurement during coronary angiography. Patients were
      followed up for MACE including all-cause death, myocardial infarction, hospital
      admission for heart failure and target vessel remote revascularization. Median hs
      cTnI and NT-proBNP values were 4 ng/L and 85 ng/L, respectively. Regional CFR was
      significantly albeit weakly correlated with hs-cTnI and NT-proBNP, while
      fractional flow reserve (FFR) was only linked to hs-cTnI. The addition of hs-cTnI
      and NT-proBNP on clinical backgrounds and angiographic score significantly
      improved predictive accuracy for MACE incidence, and further consideration of FFR
      and CFR could refine the model. The combined stratification using hs-cTnI, NT
      proBNP, FFR and CFR could efficiently stratify patient risk for MACE. In patients
      with stable CAD, integrated assessment of cardiac biomarkers and physiological
      indices could be useful for predicting future cardiovascular events.

PMID- 30229411
TI  - Far-infrared therapy improves ankle brachial index in hemodialysis patients with
      peripheral artery disease.
AB  - Ankle brachial index (ABI) is a diagnostic tool for peripheral artery disease
      (PAD), which is an important issue in hemodialysis (HD) patients. We enrolled 198
      maintenance HD patients in this study. PAD is defined as ABI <= 0.90. Only PAD
      patients received far-infrared (FIR) therapy using the WS TY101 FIR emitter for
      40 min during each HD session, three times weekly for 6 months. The ABI was
      measured at the bilateral lower extremities for 4 times [pre-dialytic timing (0
      min) and 40 min after the initiation of HD session at both day 0 and 6 months
      after the FIR therapy]. The primary outcome is the change in ABI. There were 51
      out of 198 patients with PAD. In comparison with the period without FIR therapy
      in the 51 PAD patients, 6 months of FIR therapy significantly improved the ABI of
      the right/left side for 0 min (from 0.77 +/- 0.19 to 0.81 +/- 0.20, p =
      0.027/0.79 +/- 0.20 to 0.81 +/- 0.17, p = 0.049), 40 min during HD (from 0.73 +/-
      0.23 to 0.83 +/- 0.19, p < 0.001/from 0.77 +/- 0.21 to 0.83 +/- 0.18, p < 0.001),
      and the incremental change between 0 and 40 min (from - 0.04 +/- 0.14 to 0.05 +/-
      0.13, p = 0.007/from - 0.05 +/- 0.13 to 0.03 +/- 0.11, p = 0.012), respectively.
      In conclusion, the application of FIR therapy for 40 min, three times weekly for
      6 months, has improved the ABI of both lower extremities, thus providing a new
      strategy of PAD treatment in HD patients.

PMID- 30229412
TI  - Influence of Palliative Care Training on Last-Year Nursing Department Students'
      Perception on Regarding Spirituality and Spiritual Care: A Single-Group Pretest
      Posttest Intervention Study.
AB  - Spiritual care is a part of integrated care and should not be considered as a
      separate aspect of palliative care. Spirituality is seen as a requirement that
      must be met for all patients. The aim of this study is to determine the influence
      of palliative care on the perception levels of student nurses regarding
      spirituality and spiritual care. The research was carried out as a single-group
      pretest-posttest intervention study. The study was conducted with 70 student
      nurses. Data were collected via personal information form and spirituality and
      spiritual care grading scale (SSCGS). Frequency, percentage, average, standard
      deviation, paired sample t-test and Wilcoxon test were used to analyze the data.
      55.7% of the students who participated in research stated that they had never
      heard of spiritual care, and 81.4% of the students stated that they had not
      obtained any information regarding spiritual care. The point average of the
      student nurses related to SSCGS was found to be 3.27 +/- 0.21 before training and
      3.35 +/- 0.22 after training. The difference between the total point averages of
      the student nurses pre- and posttraining was found to be statistically
      significant (p < 0.05).As a result of the research, the perception of the student
      nurses regarding spirituality and spiritual support was found to be above the
      middle and increased significantly after the training. In accordance with these
      results, it is suggested that spiritual care training should be included more
      into nursing education.

PMID- 30229413
TI  - Belief in God's Help During Hepatitis C: A Qualitative Study on Muslim Patients
      in Pakistan.
AB  - Religious/spiritual beliefs play an important role in nursing of patients during
      chronic condition. Religion comprises an institutionalized set of transcendent
      ideas, while spirituality is personal and subjective dimension of religious
      experience in search of sacred (Hill and Pargament in Psychol Relig Spiritual
      S(1):3-17, 2008). The prevailing literature describes the influential impact of
      religiosity/spirituality on coping with chronic disease, but specifically
      patients with chronic liver disease (CLD) have not been studied in Pakistani
      context. This study examined the patients' belief in religious/spiritual coping,
      role of religious/spiritual beliefs and prayer as coping strategy. Furthermore,
      it explored the importance of religious/spiritual beliefs in diverting attention
      from pain and other needs of CLD patient. A total of 20 patients with chronic
      liver disease were selected through an appropriate screening process.
      Subsequently, in-depth detailed interviews were conducted to gather experiences
      of the hepatitis patients. Religious/spiritual beliefs put forth multiple
      positive effects that help in coping with chronic hepatitis C. It has been found
      that patients of hepatitis C use prayer as a coping strategy. Religious/spiritual
      beliefs have been found as source of diverting attention from pain for the
      patients suffering from chronic hepatitis C.

PMID- 30229414
TI  - The use of indocyanine green during robotic ureteroenteric reimplantation for the
      management of benign anastomotic strictures.
AB  - PURPOSE: We describe our technique for using intraureteral and intraurinary
      diversion indocyanine green (ICG) during robotic ureteroenteric reimplantation
      and report our outcomes. METHODS: We retrospectively reviewed eight patients who
      underwent ten robotic ureteroenteric reimplantations between August 2013 and July
      2017. ICG was injected antegrade and/or retrograde into the lumen of the ureter,
      and retrograde into the lumen of the urinary diversion. All patients consented to
      off-label use of ICG. Postoperatively, all patients were assessed for: clinical
      success: the absence of flank pain; and radiological success: the absence of
      obstruction on renal scan and/or loopogram. RESULTS: Visualization of ICG under
      near-infrared fluorescence allowed for precise identification of the strictured
      ureter and urinary diversion, which fluoresced green; and localization the
      ureteroenteric stricture margins, which poorly fluoresced green. The median
      operative time was 208 min (IQR 191-299), estimated blood loss was 125 ml (IQR 69
      150), and length of stay was 6 days (IQR 1-8). Three of eight (37.5%) patients
      suffered a minor (Clavien <= 2), and 2/8 (25.0%) patients suffered a major
      (Clavien > 2) post-operative complication. There were no complications related to
      ICG use. At a median follow-up of 29 months (IQR 21-38), 8/10 (80.0%)
      ureteroenteric reimplantations were clinically and radiologically successful.
      CONCLUSIONS: Intraureteral and intraurinary diversion ICG may be utilized as a
      real-time contrast agent during robotic ureteroenteric reimplantation to assist
      with identification of the strictured ureter and urinary diversion, and
      delineation of the ureteroenteric stricture margins. Despite this, RUER remains a
      technically difficult and morbid procedure.

PMID- 30229416
TI  - Prognostic Significance of Albumin-Globulin Score in Patients with Operable Non
      Small-Cell Lung Cancer.
AB  - OBJECTIVE: This study was designed to evaluate the prognostic value of the
      preoperative albumin-globulin score (AGS) in the patients with non-small cell
      lung cancer (NSCLC) after pulmonary lobectomy. METHODS AND RESULTS: The optimal
      cutoff level was 40.00 and 27.05 g/L for Alb and Glb, respectively. Based on this
      and the previous study, patients with both an hypoalbuminemia (< 40.00 g/L) and
      an elevated Glb level (>= 27.05 g/L) were assigned a score of 2, and patients
      with one or neither were assigned a score of 1 or 0, respectively. We
      investigated the correlations between the AGS and the clinicopathological
      characteristics of patients and found that AGS was significantly associated with
      TNM stage (P = 0.016). Multivariate Cox analyses indicated that the AGS was an
      independent prognostic indicator for NSCLC for disease-free survival (DFS) (P =
      0.001) and overall survival (OS) (P = 0.004). Kaplan-Meier analysis and log-rank
      test demonstrated that there were significant differences in DFS (P < 0.001) and
      OS (P < 0.001) among the three AGS groups. Furthermore, our study showed that DFS
      and OS are significantly different in three groups of patients with different
      AGS, in both Squamous carcinoma (P < 0.001 for DFS; P < 0.001 for OS) or
      adenocarcinoma (P = 0.034 for DFS; P = 0.035 for OS). In addition, we enrolled 53
      patients as an independent set of cases for the further validation of AGS.
      Multivariate analyses verified AGS was an independent prognostic factor for NSCLC
      patients (P = 0.020 for DFS; P = 0.018 for OS). CONCLUSIONS: Preoperative AGS is
      an independent prognostic factor for patients with operable NSCLC.

PMID- 30229415
TI  - Supplementation in mushroom crops and its impact on yield and quality.
AB  - Mushroom supplementation is an agronomic process which consists of the
      application of nutritional amendments to the substrates employed for mushroom
      cultivation. Different nitrogen and carbohydrate rich supplements have been
      evaluated in crops with a substantial impact on mushroom yield and quality;
      however, there is still controversy regarding the nutritional requirements of
      mushrooms and the necessity for the development of new commercial additives. The
      addition of external nutrients increases the productivity of some low-yielding
      mushroom varieties, and therefore is a useful tool for the industry to introduce
      new commercially viable varieties. Spent mushroom compost is a waste material
      that could feasibly be recycled as a substrate to support a new commercially
      viable crop cycle when amended with supplements. On the other hand, a new line of
      research based on the use of mushroom growth promoting microorganisms is rising
      above the horizon to supplement the native microbiota, which appears to cover
      nutritional deficiencies. Several supplements employed for the cultivated
      mushrooms and their agronomic potential in terms of yield and quality are
      reviewed in this paper as a useful guide to evaluate the nutritional requirements
      of the crop and to design new formulas for commercial supplementation.

PMID- 30229417
TI  - Liver Resection for Neuroendocrine Metastases and the Obligation to Individualize
      Care.

PMID- 30229418
TI  - Resectable Distal Pancreas Cancer: Time to Reconsider the Role of Upfront
      Surgery.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly utilized to optimize
      survival in proximal pancreatic adenocarcinoma. However, few studies have
      explored the impact of NAC in distal pancreas cancer. METHODS: Patients with
      resectable pancreatic adenocarcinoma of the body or tail treated with either
      upfront pancreatectomy or NAC followed by surgery were identified in the 2006
      2014 National Cancer Database. Trends in utilization, predictors of use, and
      impact of NAC on overall survival were determined. RESULTS: Of 1485 patients, 176
      (11.9%) received NAC. Use of NAC increased from 9.3% in 2006 to 16.9% in 2013
      [odds ratio 1.14; 95% confidence interval (CI) 1.05-1.24; p = 0.001]. NAC
      patients were younger, had higher clinical stage, and preoperative CA 19-9 levels
      (all p < 0.05). After adjustment for patient-, tumor-, and treatment-related
      factors, increased clinical stage was the greatest independent predictor of
      neoadjuvant approach (p < 0.001). On multivariable analysis, survival benefit
      from NAC did not reach threshold of significance (95% CI 0.66-1.04; p = 0.10) for
      the entire cohort. However, NAC was associated with a significant survival
      advantage in clinical stage III with a 51% decreased yearly risk of death
      (adjusted hazard ratio 0.49; 95% CI 0.25-0.98; p = 0.04). A trend towards
      improved survival with NAC was observed among stage IIA (p = 0.09) and IIB (p =
      0.07) patients. CONCLUSIONS: Neoadjuvant chemotherapy is associated with improved
      overall survival in Stage III distal pancreatic adenocarcinoma and shows promise
      in earlier stage disease. However, only a small percentage of patients receive
      NAC. Prospective evaluation of NAC in distal pancreatic adenocarcinoma is
      warranted based on these findings.

PMID- 30229419
TI  - Evaluation, Staging, and Surgical Management for Adrenocortical Carcinoma: An
      Update from the SSO Endocrine and Head and Neck Disease Site Working Group.
AB  - This is the first of a two-part review on adrenocortical carcinoma (ACC), a rare
      and aggressive malignancy that often presents at an advanced stage. Most patients
      present with symptoms related to cortisol and/or androgen excess. Appropriate
      biochemical evaluation and imaging is important in assessing the extent of
      disease, operative planning, and oncologic surveillance for patients with ACC.
      For patients with locoregional disease, potential cure requires margin-negative
      resection, and accumulating evidence suggests that regional lymphadenectomy
      should be performed. Although laparoscopic adrenalectomy is reported by some to
      be adequate for localized ACC, open resection in the hands of an experienced
      adrenal surgeon is the gold standard for operative management of this disease.
      Cure is rare following disease relapse, however select patients with severe
      symptoms related to hormone excess or pain may benefit from resection of local or
      distant recurrence. For best oncologic outcomes, it is recommended that all
      patients with ACC be treated at centers with multidisciplinary expertise in
      management of this rare and aggressive malignancy.

PMID- 30229420
TI  - Opportunistic bone density screening for the abdominal radiologist using colored
      CT images: a pilot retrospective study.
AB  - PURPOSE: The purpose of the study was to develop an accurate and reproducible
      method for detecting low spinal bone density on abdominal CT images. METHODS: For
      this IRB-approved HIPAA-compliant single-center retrospective study, nonenhanced
      CT images of the lower abdomen were obtained in 631 African-American
      participants. Mean attenuation of L3/L4 was associated with quantitative CT bone
      density (QCT) in a randomly selected training cohort (N = 511), and receiver
      operating characteristics analysis was used to identify the optimal mean
      attenuation threshold for differentiating normal from low bone density. Custom
      image processing software was used to generate grayscale and colored CT images of
      the midline spine, with green for normal and red for low bone density. Five
      radiologists independently assessed bone density at L3/L4 in a validation cohort
      (N = 120) using various methods: QCT, visual assessment of sagittal grayscale
      images (Grayscale), quantitative measurement of mean attenuation on a midline
      sagittal image (Attenuation), and visual assessment of a midline sagittal colored
      image (Color). Accuracy was calculated using the average QCT bone density as a
      reference standard. Inter-observer agreement was assessed using intraclass
      correlation coefficient (ICC). RESULTS: The optimal mean attenuation threshold
      for differentiating normal from low bone density at L3/L4 was 145 Hounsfield
      Units. The average accuracy of Grayscale, Attenuation, and Color methods was 58,
      87, and 91% (p < 0.001), respectively. Inter-observer agreement was poor for
      Grayscale (ICC: 0.20; 95% CI 0.12, 0.28) and excellent for both Attenuation (ICC:
      0.85; 95% CI 0.73, 0.91) and Color methods (ICC: 0.87; 95% CI 0.83, 0.90).
      CONCLUSION: Detection of low spinal bone density using colored abdominal CT
      images was highly accurate and reproducible.

PMID- 30229421
TI  - Hepatocellular carcinoma: preoperative gadoxetic acid-enhanced MR imaging can
      predict early recurrence after curative resection using image features and
      texture analysis.
AB  - PURPOSE: To investigate whether pre-operative gadoxetic acid-enhanced MRI can
      predict early recurrence after curative resection of single HCC using image
      features and texture analysis. MATERIALS AND METHODS: 179 patients with single
      HCC and who underwent pre-operative MRI were included. Two reviewers analyzed MR
      findings, including the tumor margin, peritumoral enhancement, peritumoral
      hypointensity on the hepatobiliary phase (HBP), diffusion restriction, capsule,
      tumoral fat, washout, portal-vein thrombus, signal intensity on HBP, and
      satellite nodule. Texture analysis on the HBP was also quantified. A multivariate
      analysis was used to identify predictive factors for early recurrence,
      microvascular invasion (MVI), and the tumor grade. RESULTS: For early recurrence,
      satellite nodule, peritumoral hypointensity, absence of capsule, and GLCM ASM
      were predictors (P < 0.05). For MVI, satellite nodule, peritumoral hypointensity,
      washout, and sphericity were predictors (P < 0.05). Satellite nodules,
      peritumoral hypointensity, diffusion restriction, and iso to high signal
      intensity on HBP were predictor for higher tumor grade (P < 0.05). Satellite
      nodules and peritumoral hypointensity were important showed common predictors for
      early recurrence, MVI, and grade (P < 0.05). The sensitivity and specificity for
      satellite nodule were 47.36% and 96.25%. When added texture variables to MRI
      findings, the diagnostic performance for predicting early recurrence is improved
      from 0.7 (SD 0.604-0.790) to 0.83 (SD 0.787-0.894). CONCLUSION: MR finding,
      including satellite nodule and peritumoral hypointensity on the HBP, as well as
      the texture parameters are useful to predict not only early recurrence, but also
      MVI and higher grade.

PMID- 30229422
TI  - Hypoenhancing prostate cancers on dynamic contrast-enhanced MRI are associated
      with poor outcomes in high-risk patients: results of a hypothesis generating
      study.
AB  - PURPOSE: To investigate the association of hypoenhancement on dynamic Contrast
      enhanced (DCE) with prostate cancer patient outcomes. MATERIAL AND METHODS: This
      was a single-institution retrospective Institutional Review Board (IRB)-approved
      cohort study of 54 men who had prostate Magnetic Resonance Imaging (MRI) within 6
      months of cancer diagnosis between 01/2012 to 03/2014. Two readers independently
      identified the dominant MRI-lesions utilizing Prostate Imaging-Reporting and Data
      System-version2- guidelines. These lesions were classified as hypoenhancing or
      hyperenhancing, compared to normal peripheral zone using quantitative DCE
      analysis. The t test for unequal sample sizes and the two-sample Wilcoxon rank
      sum tests were used to compare groups. Logistic regression determined if DCE
      characteristics predict the development of metastases or prostate cancer death.
      RESULTS: Time-to-progression was significantly shorter for hypoenhancing tumors
      (6.2 vs. 24.8 months, p = 0.05). Men with these lesions had a higher odds of
      having poor outcome (univariate logistic regression, odds ratio (OR) 6.79, 95%
      confidence interval (CI) 1.45-31.72, p = 0.02; multivariate analysis, OR 2.05,
      95% CI 0.30-13.72, p = 0.47). Hypoenhancing tumors were larger (33.1 vs. 19.1 mm,
      p < 0.001) and more likely to be intermediate (Gleason scores 3 + 4 and 4 + 3)
      and high-grade (Gleason scores >= 4 + 4) prostate cancers (p = 0.05). Men in the
      hypoenhancing group had a higher mean prostate-specific antigen (PSA) value (87.6
      vs. 24.8 ng/dL, p = 0.01) and PSA density (1.54 vs. 0.72, p = 0.03). The mean
      Ktrans and kep of hypoenhancing lesion were lower when compared to hyperenhancing
      lesions (p = 0.03 and p = 0.04). Ve values did not differ (p = 0.25). CONCLUSION:
      Men with hypoenhancing prostate cancers may have a worse prognosis than men with
      hyperenhancing tumors.

PMID- 30229423
TI  - Dual-energy CT in the obese: a preliminary retrospective review to evaluate
      quality and feasibility of the single-source dual-detector implementation.
AB  - PURPOSE: To determine the feasibility of performing dual-energy CT with a single
      source spectral detector system in obese patients. MATERIALS AND METHODS:
      Retrospective, IRB-approved review of 28 patients weighing >= 270 lbs (122 kg)
      who underwent CT of the abdomen on a single-source spectral detector system was
      performed. Two blinded, independent radiologists rated relative preference
      between conventional CT images taken at 120 kVp (CCT120) and monoenergetic 70 keV
      equivalent (MonoE70) as well as iodine map image quality in the spleen, pancreas,
      kidneys, and liver. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)
      were compared between conventional CT and MonoE70 images and correlated with body
      habitus markers of weight, height, and abdominal diameter. RESULTS: MonoE70
      images were preferred by radiologists 100% of the time (1-sample t test, p <
      0.0001) over conventional CCT120 images. Noise was significantly lower; SNR and
      CNR were significantly higher in MonoE70 images than in CCT120 images (paired t
      tests, p < 0.0001). Mean iodine map rating (scale 1-5) was 4.54 +/- 0.58,
      denoting near homogenous and complete iodine mapping through the spleen,
      pancreas, kidneys, and liver for the majority of patients. Body habitus markers
      were not significantly correlated with image preference score; noise; MonoE70
      SNR; MonoE70 CNR; change in noise, SNR, or CNR from CCT120 to MonoE70, or iodine
      map quality; ordinal and linear regression, p = 0.2547, p = 0.6837, p =  0.1888,
      p = 0.5489, p = 0.9830, p = 0.8849, p = 0.8741, p = 0.1522, respectively.
      CONCLUSION: The single-source spectral detector implementation of dual-energy CT
      provides viable, high-quality imaging for obese patients.

PMID- 30229424
TI  - Imaging in the pre-operative staging of ovarian cancer.
AB  - The main prognostic factor in ovarian cancer is the stage of disease at
      diagnosis. The staging system in use (FIGO classification, updated in 2014) is
      based on the surgical-pathological findings. Although surgical staging is the
      gold standard in ovarian cancer, the initial patient management depends on the
      imaging-based pre-surgical staging assessment, in order to identify unresectable
      or difficult to resect disease. Radiologists need to be aware of the strengths of
      the available imaging modalities, as well as the imaging pitfalls. Clear
      understanding of pattern of disease spread and review areas are critical for
      accurate staging and treatment planning. The current standard of care for pre
      surgical staging is CT of the thorax, abdomen, and pelvis. This allows a rapid
      evaluation of disease extent and is fairly accurate in identifying bulky disease
      but has definite limitations in assessing the extent of small volume disease and
      in the confirmation of certain sites of disease beyond the abdomen. Functional
      MRI has been reported to be superior in detecting small peritoneal deposits.
      PET/CT may be used as a problem-solving tool in some patients where determination
      remains unclear, particularly in confirmation of advanced stage beyond the
      abdomen.

PMID- 30229426
TI  - Modeling the Spread of Zika Virus in a Stage-Structured Population: Effect of
      Sexual Transmission.
AB  - The recent Zika virus outbreak has been spreading rapidly all over the world,
      expanding its traditionally geographical affected regions, making it a global
      public health hazard and endangering millions of people. One unique property of
      the Zika virus compared to most vector-borne diseases is the fact that the virus
      is transmitted both by mosquitoes and by direct sexual contact. In the present
      manuscript, we formulate and analyze five mathematical compartmental models of
      Zika transmission. We model both transmission routes (i.e., vector-borne and
      sexual transmission). In order to make the model more realistic, heterogeneity in
      the sexual transmission is modeled in several ways. We fitted the five different
      models to data, inferred the parameters and selected the most appropriated model,
      which describes the Zika outbreak in Columbia. For all the models, we estimate
      the reproduction numbers, namely direct (sexual) transmission, vector
      transmission and the basic reproduction number [Formula: see text]. The analysis
      revealed that the sexual transmission contribution to [Formula: see text] is
      highest [15.36% (95% CI 12.83-17.4)] for the model which stratifies each gender
      to high-risk and low-risk individuals in their sexual behavior. For this model,
      the estimated [Formula: see text] is 1.89 (95% CI 1.21-2.13), the direct
      transmission reproduction number is 0.42 (95% CI 0.29-0.64), and the vector
      transmission reproduction number is 1.51 (95% CI 1.23-1.87). The sensitivity
      analysis demonstrated that the value of [Formula: see text] depends on three
      controllable parameters: the biting rate, the sexual transmission rate and the
      average ratio of mosquito to human.

PMID- 30229425
TI  - Hispanic Spinocerebellar Ataxia Type 35 (SCA35) with a Novel Frameshift Mutation.
AB  - Genetic mutations in transglutaminase 6 (TGM6) are recently identified to be
      associated with spinocerebellar ataxia type 35 (SCA35). We report a Hispanic
      SCA35 patient, who was confirmed to have a heterozygous, single-nucleotide
      deletion in TGM6, causing a frameshift mutation with a premature stop codon. An
      immune-mediated ataxia previously found to be associated with autoantibody
      reactivity to TG6 may share a similar pathomechanism to SCA35, suggesting a
      converging role for TG6 in cerebellar function.

PMID- 30229427
TI  - The Appropriate Role of a Clinical Ethics Consultant's Religious Worldview in
      Consultative Work: Nearly None.
AB  - Ethical reasoning is an integral part of the work of a clinical ethics consultant
      (CEC). Ethical reasoning has a close relationship with an individual's beliefs
      and values, which, for religious adherents, are likely to be tightly connected
      with their spiritual perspectives. As a result, for individuals who identify with
      a religious tradition, the process of thinking through ethical questions is
      likely to be influenced by their religious worldview. The connection between
      ethical reasoning and one's spiritual perspective raises questions about the role
      that CECs' personal religious worldviews should play in their professional lives
      and their consultative work. This paper offers numerous arguments critiquing the
      inclusion of a consultant's own spiritual perspective in her work and has
      identified only limited circumstances under which such inclusion might be
      permissible. In particular, these arguments lead to the conclusion that a CEC's
      personal beliefs should never influence her ethical analysis or development of a
      recommendation. Further, religious appeals should not be used in communication
      during decision-making conversations other than to describe the patient or
      surrogate's stated perspective. There may be limited cases in which a CEC may
      share her spiritual worldview with a patient with the intent of building a
      collaborative relationship, but such situations should be approached with extreme
      caution.

PMID- 30229428
TI  - Another fatal case related to the recreational abuse of U-47700.
AB  - The abuse of synthetic opioids has become a major threat in recent years. Several
      clinical reports and fatal case reports exist discussing life-threatening
      hypoventilation and fatal respiratory depression following the abuse of trans-3,4
      dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide (U-47700). The
      reported concentration of U-47700 in peripheral blood varies between 0.01 MUg/mL
      and 1.46 MUg/mL. These values depend on the mode of administration and whether
      the drug was used in combination with other drugs and/or pharmaceuticals. In the
      past, U-47700 was predominantly insufflated and not injected. The current study
      presents a non-targeted liquid chromatography/mass spectrometry (LC/MS)-based
      screening approach of urine and cerebrospinal fluid samples after intravenous
      injection of U-47700. Furthermore, quantitative values on U-47700 as obtained by
      liquid chromatography coupled to a linear ion trap (LC/ESI-QTRAPMS) are presented
      concerning femoral blood (0.29 MUg/mL), urine (0.24 MUg/mL), gastric contents
      (0.57 MUg/mL), bile fluid (2.3 MUg/mL), heart blood (1.25 MUg/mL), liver (9.9
      MUg/g), cerebrospinal fluid (0.4 MUg/mL), and hair (0.14 ng/mg). Thereof,
      concentrations in hair, gastric contents, bile fluid and cerebrospinal fluid have
      never been reported before. Drug paraphernalia were also analyzed by liquid
      chromatography coupled to a diode array detector (LC/DAD) and nuclear magnetic
      resonance spectrometer (NMR). The analyses show that the powder had a relatively
      high purity and was adulterated to a low degree. This is the first case report
      which lists concentration distributions of various specimens after intravenous
      injection. These findings as well as the U-47700 concentration are important to
      evaluate autopsy cases of U-47700 intoxication in the future.

PMID- 30229429
TI  - Use of XRD and SEM/EDX to predict age and sex from fire-affected dental remains.
AB  - In fire scenarios, the application and accuracy of traditional odontological
      methods are often limited. Crystalline studies and elemental profiling have been
      evaluated for their applicability in determining biological profiles (age and
      sex) from human dentition, particularly fire- and heat-affected dental remains.
      Thirty-seven teeth were paired according to tooth type and donor age/sex for the
      analysis of crown and root surfaces pre- and post-incineration using X-ray
      diffraction (XRD) and scanning electron microscopy (SEM/EDX). In unburned crowns,
      carbon (C) content showed a positive correlation with age, whereas phosphorus (P)
      and calcium (Ca) contents showed a negative correlation with age. In unburned
      roots, C, P and Ca contents also showed significant changes that were opposite of
      those observed in the crowns. In relation to sex, females exhibited a higher C
      ratio than males, whereas males showed significantly higher levels of oxygen (O),
      P and Ca in unburned roots. Incineration resulted in an increase in the
      crystallite size that correlated with increasing temperature. No differences in
      hydroxyapatite (HA) crystallite size were found between age groups; however,
      unburned teeth from females exhibited a larger crystallite size than did those
      from males. The challenges of using XRD with a 3D sample were overcome to allow
      analysis of whole teeth in a nondestructive manner. Further studies may be useful
      in helping predict the temperature of a fire.

PMID- 30229430
TI  - Synergistic Anticancer Effect of a Combination of Paclitaxel and 5
      Demethylnobiletin Against Lung Cancer Cell Line In Vitro and In Vivo.
AB  - Lung cancer remains a highly prevalent disease and a leading cause of cancer
      related deaths worldwide. Currently, exploring antitumor drugs derived from herbs
      used in traditional Chinese medicine is increasingly becoming an attractive area
      of research. Paclitaxel (PTX), a highly effective chemotherapeutic drug, is
      widely used for treating different cancers; however, the clinical use of PTX is
      dose limited because of its adverse side effects. Chemotherapeutic agents are
      being developed to enhance the anticancer activity of PTX, particularly for use
      in combination therapy. 5-Demethylnobiletin (5-DMN), a natural, active compound
      isolated from orange peel, has been reported to induce apoptosis in several
      cancer cell lines. In this study, we tested the synergistic anticancer
      antiproliferative effects of combinations of PTX and 5-DMN on CL1-5 lung cancer
      cells through the MTT and propidium iodide assays. After low-dose combination
      treatments (PTX and 5-DMN), a reduction in cell viability and a concomitant
      increase in apoptosis were observed in the CL1-5 cells. We propose that 5-DMN
      cooperates with PTX to induce apoptosis via the caspase pathway (by modulating
      caspase-3, caspase-8, and caspase-9 activities). Furthermore, we observed that
      the combination treatment significantly suppressed tumor growth in the nude mouse
      xenograft model. The results suggest that the synergistic effects of PTX and 5
      DMN in lung cancer cells deserve particular attention and indicate the
      possibility of developing additional new strategies for treating lung cancer.

PMID- 30229431
TI  - Synthesis and Pharmacological Evaluation of Novel Selenoethers Glycerol
      Derivatives for the Treatment of Pain and Inflammation: Involvement of Nitrergic
      and Glutamatergic Systems.
AB  - In the present study, the synthesis of new selenoethers from nucleophilic
      substitution reaction between organyl halides and nucleophilic species of
      selenium generated in situ was demonstrated. After, this method was applied for
      the synthesis of pyridylselenides glycerol derivatives 9b and 9c and the
      antinociceptive and anti-inflammatory effects, as well as, acute toxicity were
      evaluated. In the formalin test, the compound 9b caused a reduction in licking
      time in both phases. Compounds 9b and 9c increased the latency to response in the
      hot-plate test and reduced the licking time induced by glutamate. Our results
      revealed the involvement of the nitrergic and/or glutamatergic pathways in the
      antinociceptive action of the compounds. Additionally, 9b and 9c did not cause
      any toxicity signals and oxidative stress parameters were not modified by
      treatments. Here, it was developed an alternative and efficient method for the
      synthesis of selenoethers glycerol derivatives. Furthermore, we demonstrated that
      this class is indeed interesting for the research of new drugs. Graphical
      Abstract ?.

PMID- 30229432
TI  - Establishment of a DGKtheta Endogenous Promoter Luciferase Reporter HepG2 Cell
      Line for Studying the Transcriptional Regulation of DGKtheta Gene.
AB  - DGKtheta protein expression levels are closely related to the development of
      diseases including diabetes, cancer, and neuronal disease. To investigate the
      transcriptional regulation of the DGKtheta gene, we used CRISPR/Cas9 to generate
      a DGKtheta endogenous promoter luciferase reporter HepG2 cell line, in which the
      endogenous DGKtheta promoter controls the expression of the luciferase reporter
      gene. To test the cell line, FXR, the transcription factor for upregulating the
      expression of DGKtheta gene, was used to validate the cell line. Furthermore, the
      reported agonists for the expression of DGKtheta, cAMP and GW4064, the known
      inhibitor for DGKtheta enzyme activity, R59949, and a potential regulator for
      DGKtheta enzyme expression, EGCG (the major catechin in green tea), were applied
      to the reporter cell line. The results indicated that these reagents could
      significantly regulate the expression of reporter luciferase. Finally, four
      transcription factors (E2F1, c-Myc, USF1, and Bmal1) potentially binding to the
      DGKtheta gene's upstream promoter region were tested. DGKtheta expression was
      upregulated by c-Myc and downregulated by E2F1, which was also confirmed in wild
      type HepG2 cells. We found that the cell line's luciferase activity was directly
      correlated with DGKtheta endogenous promoter activity, suggesting that it is
      liable and sensitive for studying DGKtheta transcriptional regulation. The study
      provides a useful tool for high-throughput drug screening for the treatment of
      DGKtheta-involved diseases.

PMID- 30229433
TI  - Stimulation of Wood Degradation by Daedaleopsis confragosa and D. tricolor.
AB  - Biological pretreatment of the lignocellulosic residues, in which white-rot fungi
      have a crucial role, has many advantages compared to the chemical, physical, and
      physico-chemical methods of delignification and therefore attracts increasing
      scientific attention. Regarding the fact that properties and capacities of the
      ligninolytic enzymes of Daedaleopsis spp. are still unknown, the aim of this
      study was to research how nitrogen sources and inducers affect the potential of
      Daedaleopsis confragosa and Daedaleopsis tricolor to degrade cherry sawdust.
      NH4NO3, (NH4)2SO4, and peptone were tested as nitrogen sources, while veratryl
      alcohol, p-anisidine, vanillic acid, and phenylmethylsulfonyl fluoride were the
      studied inducers. As Mn-dependent peroxidase and laccase were the leader enzymes
      and cherry sawdust/peptone medium the best stimulator of their activities, the
      effect of inducers on delignification potential of these species was studied
      during fermentation of that substrate. Veratryl alcohol was the best stimulator
      of laccase and phenylmethylsulfonyl fluoride of Mn-dependent peroxidase activity
      (27,610.0 and 1338.4 U/L, respectively). These inducers also increased cherry
      sawdust delignification selectivity, particularly in D. tricolor in the presence
      of phenylmethylsulfonyl fluoride (lignin:hemicellulose:cellulose =
      32.1%:0.9%:11.7%). Owing to the presented results, studied species could have an
      important role in the phase of lignocellulose pretreatment in various
      biotechnological processes.

PMID- 30229434
TI  - In Vitro Studies on Ameliorative Effects of Limonene on Cadmium-Induced
      Genotoxicity in Cultured Human Peripheral Blood Lymphocytes.
AB  - Cadmium (Cd) is a non-redox metal that can indirectly cause oxidative stress by
      depleting cellular levels of glutathione. It is well-known for the generating
      reactive oxygen species (ROS) such as hydroxyl radicals, superoxide anions,
      nitric oxide, and hydrogen peroxide. The latter inactivates antioxidant enzymes
      and induces lipid peroxidation and DNA damage in cells. In our study, we have
      investigated the ameliorative effect of limonene against Cd-induced genotoxicity
      using various biomarkers such as sister chromatid exchange (SCE), comet, and
      lipid peroxidation (LPA) assays in cultured human peripheral blood lymphocytes
      (PBL) from healthy individuals. It is a naturally occurring flavonoid, found in
      essential oil of citrus fruits. Limonene at 20-MUM and 100-MUM concentrations had
      significantly (P < 0.05 and P < 0.01) reduced the SCE frequency, tail moment, and
      peroxidation of lipids. Ameliorative effect of limonene was also determined by
      measuring the activity of antioxidant enzymes such as superoxide dismutase (SOD)
      and catalase (CAT). We found a significant increase (P < 0.05) in the enzyme
      activity after limonene treatment. We also studied the effect of GSTP1 gene
      polymorphism on Cd-induced genotoxicity and antigenotoxic potential of limonene.
      We found a significant decrease (P < 0.05) in SCE frequency, tail moment, and
      lipid peroxidation after limonene treatment compared to Cd. However, we did not
      observe any significant relationship (P > 0.05) between GSTP1 polymorphism and
      Cd, limonene genotoxicity and antigenotoxicity, respectively.

PMID- 30229435
TI  - An Insight into the Anaerobic Co-digestion of Municipal Solid Waste and Food
      Waste: Influence of Co-substrate Mixture Ratio and Substrate to Inoculum Ratio on
      Biogas Production.
AB  - The unbalanced nutrients of municipal solid waste (MSW), particularly high carbon
      contents, were regarded as a major limiting factor to anaerobic digestion
      process. In this study, the addition of MSW in food waste (FW) feedstock to have
      a balanced C/N ratio was studied. Different co-substrate mixtures with C/N ratio
      of 20 to 40 were subjected to anaerobic batch experiment at lab scale, under
      mesophilic conditions. The biogas production decreased with the increase in C/N
      ratio due to insufficient availability of organic nitrogen for anaerobic
      microbial growth. Specific biogas and methane yields were observed to be 827 and
      474.44 mL g-1VS, respectively, with volatile solids (VS) reduction rate of 88%,
      at C/N ratio of 20. Furthermore, the effect of the substrate to inoculum (S/I)
      ratio on digester performance was also studied. The biogas production decreased
      with the increase in S/I ratio due to the formation of more volatile fatty acids
      (VFAs) which led to decrease in pH and accumulated unionized ammonia-N. Specific
      biogas and methane yields were recorded to be 655 and 410.20 mL g-1VS, with 64%
      rate of biodegradability at S/I ratio of 0.5. Kinetics and statistics study
      showed that the higher S/I ratio could lead to VFA accumulation and result in low
      methane yield.

PMID- 30229437
TI  - Thoracoscopic resection of mediastinal tumor in a patient with azygos
      continuation of the inferior vena cava.
AB  - A 68-year-old man was referred to our hospital because of mediastinal tumor on
      chest computed tomography (CT). Contrast-enhanced CT showed azygos continuation
      of the inferior vena cava (IVC). The retro-hepatic IVC was absent superior to the
      renal veins. The IVC continued into the dilated azygos vein, which joined the
      superior vena cava. The hepatic vein drained directly into the right atrium. The
      mediastinal tumor was close to the dilated azygos vein. Video-assisted
      thoracoscopic resection of the mediastinal tumor was performed, using four ports
      and CO2 insufflation. Histological examination of the resected specimen revealed
      a pericardial cyst without malignancy. After a favorable postoperative course,
      the patient was discharged 4 days after surgery. It is important to recognize
      this anomaly before thoracic surgery, because transection of the azygos vein can
      be fatal. Video-assisted thoracoscopic resection of mediastinal tumor close to
      the azygos vein using CO2 insufflation avoids injury to the azygos vein.

PMID- 30229436
TI  - The FOXP3 rs3761547 Gene Polymorphism in Multiple Sclerosis as a Male-Specific
      Risk Factor.
AB  - The FOXP3 gene encodes a transcription factor and is predominantly expressed in
      the CD4+CD25+ regulatory T cells which plays a pivotal role in the maintenance of
      immune homeostasis. The defect of FOXP3 gene may provide a critical link between
      autoimmunity and immune deficiency. The purpose of our study was to evaluate the
      association of chosen polymorphisms of FOXP3 gene (rs3761549, rs3761548,
      rs3761547) with different clinical multiple sclerosis (MS) data of our relapsing
      remitting groups of patients and in control group. The study was performed on a
      group consisting of 174 relapsing-remitting MS patients, diagnosed under 40 years
      of life, and 174 healthy volunteers. Genotyping was performed using a real-time
      PCR-based method by TaqMan Assays. Significant differences in distribution of
      allele C rs3761547 were found in male MS patients in comparison to the male
      healthy group (p = 0.046, OR 1.95, CI 95%). No association between MS and the
      other two polymorphisms was observed in males and females of both studied groups.
      Our data may suggest that FOXP3 rs3761547 gene polymorphism are related notably
      with the increased risk of MS development in males patients. To our knowledge
      this is the first study which indicates gender-specific relation between
      rs3761547 FOXP3 gene polymorphism and multiple sclerosis.

PMID- 30229438
TI  - Sodium Butyrate Exerts Neuroprotective Effects in Spinal Cord Injury.
AB  - Sodium butyrate (SB) is a dietary microbial fermentation product and serves as an
      important neuromodulator in the central nervous system. Recent experimental
      evidence has suggested potential therapeutic applications for butyrate, including
      its utility in treating metabolic and inflammatory diseases. The aim of the
      present study was to evaluate the potential beneficial effects of SB in a mouse
      model of spinal cord injury (SCI) and its possible mechanism of action. SCI was
      induced by extradural compression for 1 min of the spinal cord at the T6-7 level
      using an aneurysm clip, and SB (10-30-100 mg/kg) was administered by oral gavage
      1 and 6 h after SCI. For locomotor activity, study mice were treated with SB once
      daily for 10 days. Morphological examination was performed by light microscopy
      through hematoxylin-eosin (H&E) staining. In addition, NF-kappaB, IkappaB-alpha,
      COX-2, and iNOS expressions were assayed by western blot analysis and IL-1beta
      and TNF-alpha levels by immunohistochemistry analysis. The results showed that SB
      treatment significantly ameliorated histopathology changes and improved recovery
      of motor function changes in spinal cord injury in a dose-dependent manner.
      Moreover, we demonstrated that SB modulated the NF-kappaB pathway showing a
      significant reduction in cytokine expression. Thus, this study showed that SB
      exerts neuroprotective effects anti-inflammatory properties following spinal cord
      injury suggesting that SB may serve as a potential candidate for future treatment
      of spinal cord injury.

PMID- 30229439
TI  - The efficacy of propranolol in very preterm infants at the risk of retinopathy of
      prematurity: Which newborn and when?
AB  - PURPOSE: Retinopathy of prematurity (ROP), a proliferative vitreoretinopathy
      resulting from the vascular disorder of the retina, is the most frequent cause of
      blindness in childhood. In our time, ROP in advanced stage, a serious problem in
      premature infants, has no other treatment more effective and with fewer side
      effects than laser photocoagulation (LPC) treatment, which narrows visual field.
      The search for methods with fewer side effects than LPC has increased in recent
      times for the treatment of ROP. We aimed to investigate the effects in question
      of propranolol on ROP in various stages (stages 1, 2, and 3 ROP). METHODS: This
      study is designed as a randomized, placebo-controlled, single-centered, double
      blind clinical trial with parallel groups. A total of 126 very preterm infants,
      followed up in our unit from April 2011 to January 2013, were randomly selected
      and included in our study. They were separated into the groups of 0, 1, and 2
      depending on their stage of ROP. In addition, all the patients were divided into
      control group (CG) and propranolol treatment group (PTG). While the cases in the
      CG were administered physiological saline solution, the cases in the PTG were
      administered propranolol (2 mg/kg/day) in the neovascularization phase (second
      phase) of the ROP. RESULTS: Propranolol given to the group of stage 0-1 ROP was
      observed to have had no effect on the level of statistical significance between
      the CG and PTG in terms of increase in ROP stages (p > 0.05). However,
      propranolol was found to be more useful in patients with stage 2 ROP (p < 0.05).
      CONCLUSION: When given in the neovascularization phase of the ROP, propranolol
      was found to be effective in the stage 2 (advanced stage) ROP patients but in
      stage 0-1 (early-stage) ROP patients, its efficacy was not sufficient.

PMID- 30229440
TI  - Distinct Activity Patterns of the Human Bed Nucleus of the Stria Terminalis and
      Amygdala during Fear Learning.
AB  - The amygdala and, more recently, also the bed nucleus of the stria terminalis,
      have been widely implicated in fear and anxiety. Much of our current knowledge is
      derived from animal studies and suggests an intricate convergence and divergence
      in functions related to defensive responding. In a recent paper, Klumpers and
      colleagues set out to examine these functions in a human fear learning procedure
      using functional magnetic resonance imaging. Their main findings were a role for
      the bed nucleus of the stria terminalis in threat anticipation, and for the
      amygdala in threat confrontation. Here, we provide a critical summary of this
      interesting study and point out some important issues that were not addressed by
      its authors. In particular, we first take a closer look at the striking
      differences between both samples that were combined for the study, and, secondly,
      we provide an in-depth discussion of their findings in relation to existing
      neurobehavioral models.

PMID- 30229441
TI  - IluvienTM (Fluocinolone Acetonide 0.19 mg Intravitreal Implant) in the Treatment
      of Diabetic Macular Edema: A Review.
AB  - Diabetic macular edema (DMO) is a leading cause of blindness in the working age
      population. Although anti-vascular endothelial growth factor (VEGF) therapy
      provided a major advance in treatment of DMO for many patients, there is a
      significant proportion of patients who maintain persistent DMO and have minimal
      response to anti-VEGF treatment. Iluvien (fluocinolone acetonide 0.19 mg [FAc])
      is an important additional treatment option for DMO. In this review we describe
      the clinical context and the evidence for the use of the FAc implant in treating
      DMO, from pilot to randomized controlled studies, to later phase real world data.
      These studies indicate that the FAc implant is effective, well tolerated and a
      cost-effective option in the treatment of insufficiently responsive DMO.

PMID- 30229442
TI  - Tafenoquine: First Global Approval.
AB  - Tafenoquine (KrintafelTM, ArakodaTM), an orally-active 8-aminoquinoline anti
      malarial drug, is a long-acting analogue of primaquine with activity against pre
      erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of
      Plasmodium species that include Plasmodium vivax (P. vivax) and Plasmodium
      falciparum. It has been developed by GlaxoSmithKline (formerly SmithKline
      Beecham) for the radical cure of P. vivax malaria and by 60 Degrees
      Pharmaceuticals for the prophylaxis of malaria. The exact mechanism(s) of action
      underlying the anti-Plasmodium activity of tafenoquine are unknown, although it
      may exert its effect by inhibiting haematin polymerization and, additionally, by
      inducing mitochondrial dysfunction leading to the apoptotic-like death of the
      organism. In July 2018, tafenoquine was approved in the USA for the radical cure
      of P. vivax malaria in patients aged >= 16 years who are receiving appropriate
      antimalarial therapy for acute P. vivax malaria. Subsequently, in August 2018,
      tafenoquine was approved in the USA for the prophylaxis of malaria in patients
      aged >= 18 years. This article primarily summarizes the milestones in the
      development of tafenoquine leading to its first global approval for the radical
      cure of P. vivax malaria.

PMID- 30229443
TI  - A Prospective Cohort Study on the Management of Young Patients with Newly
      Diagnosed Type 2 Diabetes Using Mobile Medical Applications.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of using a mobile
      medical application (app) for self-monitoring of blood glucose (SMBG) and blood
      glucose control in young patients with newly diagnosed type 2 diabetes mellitus
      (T2DM). METHODS: This was a prospective cohort study involving young patients
      with newly diagnosed T2DM. On a voluntary basis, the patients chose to be
      included in a group in which they were followed up for 24 weeks with a mobile
      medical app and the changes in laboratory data and frequency of SMBG observed via
      the app, or in a group in which they received traditional medical treatment and
      follow-up. The results between the two groups were compared. RESULTS: A total of
      126 patients signed the informed consent form and were enrolled in the study, of
      whom 66 chose the mobile medical group, which used the mobile medical app, and
      the remaining 60 patients chose the traditional medical treatment model. The
      differences in the physical and chemical indicators between the app-using group
      and the traditional medical model group were not statistically significant at
      baseline (p  > 0.05). At 24 weeks of treatment, the levels of glycosylated
      hemoglobin A1c (HbA1c), total cholesterol, triglycerides, and low-density
      lipoprotein cholesterol were significantly reduced in all patients compared to
      before treatment (p  < 0.05). The app-using group had a higher HbA1c compliance
      rate and higher frequency of both SMBG and doctor-patient communication than the
      traditional medical model group (p  < 0.01). The HbA1c compliance rate of
      patients using the mobile medical app was 1.53-fold higher than that of the
      traditional medical model group. At 24 weeks, HbA1c was negatively correlated
      with the frequency of SMBG (r  = - 0.208, p  = 0.020) and the frequency of doctor
      patient communication (r  = - 0.323, p  = 0.000). Additionally, there was a
      positive correlation between the frequency of SMBG and doctor-patient
      communication (r  = 0.579, p  = 0.000). CONCLUSION: A mobile medical app is
      helpful to young patients with newly diagnosed T2DM for monitoring their blood
      glucose level and improving their blood glucose control to meet the standard.

PMID- 30229444
TI  - Electronic referrals for virtual fracture clinic service using the National
      Integrated Medical Imaging System (NIMIS).
AB  - INTRODUCTION: Virtual fracture clinics (VFC) are now prevalent across many
      orthopaedic services in the UK and Ireland. The management of a variety of
      musculoskeletal injuries using the VFC model has been demonstrated to be safe,
      cost-effective and associated with high levels of patient satisfaction. Referrals
      were made available through the National Integrated Medical Imaging System
      (NIMIS). NIMIS allows for electronic movement of patient images throughout the
      Irish health service. METHODS: A retrospective review of 157 orthopaedic fracture
      referrals from a regional hospital was performed. The referrals were received
      during a 6-week period between May 2016 and June 2016. Each of these referrals
      was sent electronically. These referrals were reviewed each day by a consultant
      led multi-disciplinary team. RESULTS: Thirty (93%) patients agreed or strongly
      agreed that they received adequate information in relation to the VFC when they
      attended the emergency department (ED). All patients except for one either agreed
      or strongly agreed that they were satisfied with their recovery (97%). Fifteen
      parents advised us that they would have had to take time off to attend fracture
      clinic with their child. Two patients attended their general practitioner (GP) or
      ED to seek further pain relief following their injuries. Only one patient
      reported a poor clinical outcome. Nine (28%) patients reported that they would
      have preferred a face-to-face appointment rather than being treated by the VFC.
      CONCLUSION: Virtual review of orthopaedic trauma patients results in satisfactory
      patient outcomes. Clinical outcomes were acceptable with minimal additional
      medical attention required following injury. Electronic transfer of information
      allows for the virtual service to operate from sites long distances from the
      primary orthopaedic centre. The NIMIS is a safe and confidential means of
      collaborating with other institutions and has huge potential in the areas of
      trauma care delivery, clinical conferencing and other image-based disciplines.

PMID- 30229445
TI  - Type 2 retear after arthroscopic single-row, double-row and suture bridge rotator
      cuff repair: a systematic review.
AB  - AIM/PURPOSE: To provide a systematic review of the literature on patterns of
      retear after single-row (SR), double-row (DR) and suture bridge (SB) techniques.
      METHODS: The PubMed and MEDLINE databases were searched for published articles
      reporting both repair technique and retear pattern. Studies in languages other
      than English, those reporting open rotator cuff repair as the index procedure, as
      well as animal and cadaveric studies and those which did not describe patterns of
      retear, were excluded. MINORS scoring system was used to quantify potential bias
      in each study. Retears were classified into type 1 (failure at the tendon-bone
      interface) and type 2 (medial cuff failure). For all studies included, number and
      type of retears after different repair techniques were reported and analyzed.
      RESULTS: Fourteen studies were included yielding a total of 260 rotator cuff
      retears. Repair technique had a significant impact on the estimated incidence
      rate of type 2 retear (p = .001). The estimated incidence rate of type 2 retear
      was 24% with SR (95% CI 14-38%), 43% with DR (95% CI 22-66%), 62% with SB (95% CI
      54-70%) and 38% with SB (95% CI 23-57%). CONCLUSION: Despite the lack of high
      quality evidence, this study suggests that DR and SB techniques increase the risk
      of medial cuff failure. Modifications in surgical techniques in both DR and SB
      repairs can help decrease that risk. LEVEL OF EVIDENCE: Level IV, systematic
      review of investigations including level IV.

PMID- 30229446
TI  - Incidence, risk factors and clinical impact of postoperative delirium following
      open reduction and internal fixation (ORIF) for hip fractures: an analysis of
      7859 patients from the ACS-NSQIP hip fracture procedure targeted database.
AB  - OBJECTIVE: Delirium is one of the most common acute psychiatric disturbances
      taking place in patients, particularly elderly, following hip fractures. Using a
      validated national surgical database, we sought to define the incidence, risk
      factors and clinical impact associated with the occurrence of delirium following
      open reduction and internal fixation (ORIF) for hip fracture. METHODS: The 2016
      American College of Surgeons-National Surgical Quality Improvement Program (ACS
      NSQIP) Hip Fracture Targeted Procedure file-was retrieved and merged with the ACS
      NSQIP 2016 file. A total of 7859 patients were finally included in the study.
      RESULTS: A total of 2177 (27.7%) patients experienced an episode of delirium
      following the procedure. Adjusted analysis showed an increasing age >= 65 years
      (p < 0.001), partially dependent functional health status prior to surgery (p =
      0.001), bleeding disorder (p = 0.012), preoperative dementia (p < 0.001),
      preoperative delirium (p < 0.001), being bed-ridden postoperatively (p < 0.001),
      no weight bearing as tolerated on first postoperative day (p < 0.001), an ASA
      grade > II (p < 0.001), non-emergency case (p = 0.010) and a prolonged length of
      stay > 3 days (p < 0.001). In addition, Black or African-American ethnicity had a
      lower odds of developing postoperative delirium (p = 0.020) as compared to
      Whites. Moreover, postoperative delirium was significantly associated with non
      home discharge disposition (p < 0.001), higher odds of 30-day readmissions (p <
      0.001) and 30-day mortality (p < 0.001). CONCLUSION: This study identifies
      several risk factors associated with the occurrence of postoperative delirium in
      patients undergoing ORIF for hip fracture. Surgeons can utilize these data to
      risk stratify and consequently tailor an appropriate preoperative and
      postoperative care protocol to prevent the occurrence of delirium.

PMID- 30229447
TI  - Immune receptor recombinations from breast cancer exome files, independently and
      in combination with specific HLA alleles, correlate with better survival rates.
AB  - PURPOSE: Immune characterizations of cancers, including breast cancer, have led
      to information useful for prognoses and are considered to be important in the
      future of refining the use of immunotherapies, including immune checkpoint
      inhibitor therapies. In this study, we sought to extend these characterizations
      with genomics approaches, particularly with cost-effective employment of exome
      files. METHODS: By recovery of immune receptor recombination reads from the
      cancer genome atlas (TCGA) breast cancer dataset, we observed associations of
      these recombinations with T-cell and B-cell biomarkers and with distinct survival
      rates. RESULTS: Recovery of TRD or IGH recombination reads was associated with an
      improved disease-free survival (p = 0.047 and 0.045, respectively). Determination
      of the HLA types using the exome files allowed matching of T-cell receptor V- and
      J-gene segment usage with specific HLA alleles, in turn allowing a refinement of
      the association of immune receptor recombination read recoveries with survival.
      For example, the TRBV7, HLA-C*07:01 combination represented a significantly
      worse, disease-free outcome (p = 0.014) compared to all other breast cancer
      samples. By direct comparisons of distinct TRB gene segment usage, HLA allele
      combinations revealed breast cancer subgroups, within the entire TCGA breast
      cancer dataset with even more dramatic survival distinctions. CONCLUSIONS: In
      sum, the use of exome files for recovery of adaptive immune receptor
      recombination reads, and the simultaneous determination of HLA types, has the
      potential of advancing the use of immunogenomics for immune characterization of
      breast tumor samples.

PMID- 30229448
TI  - NMR 1H, 13C, 15N backbone and side chain resonance assignment of the N-terminal
      domain of yeast proteasome lid subunit Rpn5.
AB  - The 26S proteasome is responsible for the selective, ATP-dependent degradation of
      polyubiquitinated proteins in eukaryotic cells. It consists of a 20S barrel
      shaped core particle capped by two 19S regulatory particle at both ends. The Rpn5
      subunit is a non-ATPase subunit located in the lid subcomplex of the 19S
      regulatory particle and is identified to inhibit the Rpn11 deubiquitinase
      activity in the isolated lid. The protein contains a C-terminal proteasome-CSN
      eIF3 (PCI) domain and an N-terminal alpha-solenoid domain, the latter has been
      shown to be highly flexible in the isolated lid and may participate in
      interactions with different subunits of the proteasome. We herein report the 1H,
      13C and 15N atoms chemical shift assignments of the N-terminal domain (residues 1
      136) of Saccharomyces cerevisiae Rpn5, which provide the basis for further
      studies of the structure, dynamics and interactions of the Rpn5 subunit by NMR
      technique.

PMID- 30229449
TI  - Backbone chemical shift assignment of macrophage infectivity potentiator
      virulence factor of Trypanosoma cruzi.
AB  - Chagas disease is a trypanosomiasis disease inflicted by Trypanosoma cruzi
      parasite. In Latin America, at least 10 million people are infected and annually,
      10,000 casualties are deplored. Macrophage infectivity potentiator protein is one
      of the major virulence factors secreted by T. cruzi (TcMIP) in order to infect
      its host but little is known about its mechanism of action. Studies confer TcMIP
      an important role in the extracellular matrix transmigration and basal lamina
      penetration. Here, we report the backbone 1H, 13C, and 15N resonance assignment
      of TcMIP and the comparison of the secondary structure obtained against reported
      X-ray crystallography data.

PMID- 30229450
TI  - 1H, 13C, and 15N resonance assignments of the C-terminal lobe of the human HECT
      E3 ubiquitin ligase ITCH.
AB  - ITCH (aka Atrophin-1-interacting protein 4) is a prominent member of the NEDD4
      HECT (Homologous to E6AP C-Terminus) E3 ubiquitin ligase family that regulates
      numerous cellular functions including inflammatory responses through T-cell
      activation, cell differentiation, and apoptosis. Known intracellular targets of
      ITCH-dependent ubiquitylation include receptor proteins, signaling molecules, and
      transcription factors. The HECT C-terminal lobe of ITCH contains the conserved
      catalytic cysteine required for the covalent attachment of ubiquitin onto a
      substrate and polyubiquitin chain assembly. We report here the complete
      experimentally determined 1H, 13C, and 15N backbone and sidechain resonance
      assignments for the HECT C-terminal lobe of ITCH (residues 784-903) using
      heteronuclear, multidimensional NMR spectroscopy. These resonance assignments
      will be used in future NMR-based studies to examine the role of dynamics and
      conformational flexibility in HECT-dependent ubiquitylation as well as
      deciphering the structural and biochemical basis for polyubiquitin chain
      synthesis and specificity by ITCH.

PMID- 30229451
TI  - 1H, 13C and 15N NMR assignments of two plant protease inhibitors (IRD7 and IRD12)
      from the plant Capsicum annuum.
AB  - Helicoverpa species are polyphagous pests, with the larval stages causing major
      damage to economically valuable crops such as cotton, tomato, corn, sorghum,
      peas, sunflower, wheat and other pulses. Over the years, Helicoverpa armigera has
      developed resistance to most classes of chemical insecticides, and consequently
      it is now largely controlled on cotton plants via the use of Bt transgenic crops
      that express insecticidal Cry toxins which in-turn expedited resistance
      development in a number of pest species including H. armigera. In a hope to
      provide other eco-friendly alternatives solutions to counter the effect of the
      pest, people have identified a number of protease inhibitors (PIs) from the
      domesticated capsicum species Capsicum annuum, several of which potently
      inhibited H. armigera gut proteases and impeded growth of H. armigera larva. With
      a view to explore and enhance the specific nature or properties of these PIs on
      the mechanism of inhibition, structural and functional characterization of these
      PIs are inevitable. Towards this goal, we have carried out complete 1H, 13C and
      15N resonance assignments of two of these PIs, identified as IRD7 and IRD12,
      using a suite of 2D and 3D multi-dimensional and multi-nuclear NMR experiments.

PMID- 30229452
TI  - The (templar) knight cap: a new and simple way to prevent hair interference
      during ear surgery.
AB  - INTRODUCTION: Hair interference is a critical problem in ear surgery. The hair
      around the surgical area can get stuck unwantedly, making the surgeon habitually
      struggling with this hair rather than the surgery itself. Hair shaving can cause
      psychological discomfort, especially for women and data about shaving efficacy
      are conflicting. With the aim of solving this problem, we developed a new way to
      clear hair from the operating field named "The (Templar) Knight cap". TECHNICAL
      DESCRIPTION: This is a medical elastic stocking open at the ear to be treated and
      at the face that recalls the typical cap worn by Templar knight. This cap allows
      good hair retention and marks the surgical site. It is easy to wear does not
      require additional time for clinical staff. CONCLUSIONS: The described cap could
      be a valid instrument during ear surgery with a low cost pricing, making it
      applicable in very poor settings, such as developing countries.

PMID- 30229453
TI  - Adherence to ATA 2015 guidelines in the management of unifocal non-invasive
      papillary thyroid cancer: a clinical survey among endocrinologists and surgeons.
AB  - BACKGROUND: Despite updated guidelines, management of thyroid nodules remains
      controversial. We aim to check implementation of new guidelines by ear-nose
      throat (ENT) surgeons and endocrinologists. METHODS: A questionnaire was e-mailed
      including demographic data and an index case: a healthy 26-year-old women with a
      3-cm Bethesda III (B3) atypia of undetermined significance solitary nodule and
      eventually papillary thyroid cancer (PTC). RESULTS: Respondent rate was 50.5%, 93
      endocrinologists, 55 surgeons. For this case, 77.4% would repeat fine-needle
      aspiration (FNA), 25.3% order molecular analysis and 22.6% do surgery. If
      repeated FNA remained B3, 51% would choose surgery, 17.3% molecular analysis and
      31.6% follow-up only. If repeated FNA was B6, 58.5% would recommend total (TTx)
      and 41.5% hemithyroidectomy (HTx). In pathologically confirmed PTC after HTx,
      42.4% would recommend completion, 26.8% radioactive iodine (RAI) treatment. For a
      > = 4-cm tumor, 49.2% would recommend TTx. For a tumor 2-4 cm, 41% would
      recommend TTx. Variables favoring TTx were family history and radiation exposure.
      Only 17.4% would prefer TTx when small benign contralateral tumor is present.
      Reassessment at 1 year with undetectable thyroglobulin (Tg) included stimulated
      Tg (stTg) (72.5%), neck US only (27.5%) and combined US-stTg (59.4%); only 10.3%
      would order a diagnostic scan. For recurrence in two (13-9 mm) lymph nodes, 59.3%
      recommend reoperation, 16.3% RAI and 24.4% active surveillance. There were no
      major differences between endocrinologists and ENT surgeons. CONCLUSIONS: We
      report a considerable lack of adherence to new guidelines, with only 50%
      recommending HTx for a 4-cm unifocal low-risk PTC tumor.

PMID- 30229454
TI  - Cervical inlet patch: an important cause of Globus pharyngeus.

PMID- 30229455
TI  - Electrolyte balance and voice in hemodialysis patients.

PMID- 30229456
TI  - Impact of cochlear implantation on the management strategy of patients with
      neurofibromatosis type 2.
AB  - PURPOSE: To investigate the outcomes of cochlear implantation in patients with
      neurofibromatosis type 2 (NF2), and to discuss the current management strategy
      for NF2 patients. METHODS: The medical records of NF2 patients who received
      cochlear implants (CI) at our center between 2012 and 2016 were retrospectively
      reviewed. Pre-operative hearing status, tumor status, treatment of tumors, and
      auditory outcomes post-implantation were evaluated. RESULTS: Twelve patients were
      included in the study. Five were implanted with the tumor in situ; two of them
      received radiotherapy pre-implantation, and three were implanted without any
      previous treatment. Four patients were implanted simultaneously with tumor
      removal. Three patients were implanted as second-stage after failed hearing
      preservation surgery. The mean pure tone audiometry with the implant was 44 dB
      (range 25-80 dB) and the mean sentence recognition score (SRS) in a quiet
      environment without lip reading was 63% (range 0-97%). A poorer objective
      auditory outcome was identified in one patient who showed no response to
      electrical promontory stimulation (EPS), but the sound perception was still
      helpful. In total, 11 of 12 (91%) patients were daily users, and the other
      patient used the implant as a "sleeper" device due to its interference with
      contralateral hearing provided by a hearing aid. CONCLUSION: CI is an effective
      option in auditory rehabilitation and should be considered primarily for NF2
      patients with intact cochlear nerve. EPS might be a predictor for cochlear
      implant performance. Good contralateral hearing may present a barrier to daily
      use.

PMID- 30229457
TI  - Cartilaginous Eustachian tube length and carotid canal dehiscence in children: a
      radiological study.
AB  - PURPOSE: The use of Balloon Eustachian tuboplasty (BET) for Eustachian tube
      dysfunction is increasing in adults but to a lesser extent in children. Despite
      growing experience, concerns remain that BET could theoretically cause carotid
      artery rupture, which may be more likely if there is carotid canal dehiscence
      adjacent to the bony Eustachian tube. This radiological study aims to assess the
      prevalence of carotid canal dehiscence and length of cartilaginous Eustachian
      tube in children. MATERIALS AND METHODS: 75 consecutive computed tomography scans
      of the petrous temporal bones performed in children were identified (150 carotid
      canals/Eustachian tubes). Two independent raters measured the length of the
      cartilaginous Eustachian tube and thickness of carotid canal wall. RESULTS: 8% of
      carotid canals had radiological dehiscence. Prevalence of carotid canal
      dehiscence on either side per child was 12%. Mean cartilaginous Eustachian tube
      length was 24.5 mm (SD 3.1 mm) and the minimum measured was 14.1 mm. The minimum
      length measured in a child over 3 years old (n = 65) was 18.1 mm. The mean
      thickness of bone of the carotid canal was 0.7 mm (SD 0.27 mm). There was a
      positive relationship between age and Eustachian tube length (Pearson's
      correlation coefficient = 0.622, p < 0.001). CONCLUSIONS: Carotid canal
      dehiscence in children has a low prevalence. Variation in the length of the
      cartilaginous Eustachian tube is low but is correlated with age. More research is
      required to define the indications, safety, efficacy and technical aspects of BET
      in children.

PMID- 30229459
TI  - Acral Melanoma: A Patient's Experience and Physician's Commentary.
AB  - This article, co-authored by a patient diagnosed with acral melanoma, discusses
      the patient's experience of being diagnosed with and treated with surgery for
      this disease. The physician discusses the epidemiology, genetics, diagnosis,
      treatment, and prognosis of acral melanoma. Follow-up care plans are also
      discussed.

PMID- 30229458
TI  - Asymmetric hearing loss and the benefit of cochlear implantation regarding speech
      perception, tinnitus burden and psychological comorbidities: a prospective follow
      up study.
AB  - OBJECTIVES: We determined the audiological outcome, the subjective and objective
      hearing quality in patients suffering from asymmetric hearing loss (AHL).
      Furthermore, we evaluated psychological comorbidities and tinnitus burden before
      and after cochlear implantation. STUDY DESIGN: Prospective cohort study. METHODS:
      44 AHL patients were unilaterally implanted with a multichannel cochlear implant
      between 2011 and 2016. Speech discrimination (Freiburg Monosyllable Word Test,
      Oldenburg Sentence Test) was measured before, 6 and 12 months after implantation.
      Subjective hearing quality, health-related quality of life (HRQoL), tinnitus
      burden, anxiety, depressiveness, perceived stress level and coping abilities were
      evaluated before implantation, 6 and 12 months postoperative using specific
      validated questionnaires (Oldenburg Inventory, Nijmegen Cochlear Implantation
      Questionnaire, Tinnitus Questionnaire, General Anxiety Disorder-7, Depression
      Scale, Perceived Stress Questionnaire and Cope Inventory). RESULTS: Subjective
      and objective hearing quality, speech discrimination and health-related quality
      of life were significantly increased in AHL patients. Tinnitus burden
      significantly decreased over the 12 postoperative months. No significant
      alteration was observed for anxiety, depressiveness, coping abilities and stress
      level. CONCLUSIONS: This study demonstrates that cochlear implantation achieves
      hearing rehabilitation, increases HRQoL and decreases tinnitus burden in patients
      suffering from AHL. Subjective hearing quality increased, while tinnitus burden
      significantly decreased 6 and 12 months after implantation. HRQoL in AHL patients
      is an important factor to focus on and is significantly increased
      postoperatively. In contrast, general anxiety, depressiveness, coping abilities
      and perceived stress level remained unaffected.

PMID- 30229460
TI  - Effect of Body Mass Index, Metabolic Health and Adipose Tissue Inflammation on
      the Severity of Non-alcoholic Fatty Liver Disease in Bariatric Surgical Patients:
      a Prospective Study.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), driven by the obesity
      epidemic, has become the most common form of liver disease. Despite this, there
      is controversy regarding the prevalence and severity of NAFLD in obesity. Obesity
      related factors, such as increasing adiposity, metabolic disease and
      inflammation, may influence prevalence. We therefore prospectively measured NAFLD
      prevalence in obesity and studied factors associated with NAFLD. MATERIALS AND
      METHODS: We recruited consecutive bariatric patients. Intraoperative liver
      biopsies were taken. The liver, adipose tissue and serum were collected to
      measure inflammation. Adipocyte cell size was measured. NAFLD severity was
      correlated to body mass index (BMI), metabolic health and adipose
      characteristics. RESULTS: There were 216 participants; BMI 45.9 +/- 8.9 kg/m2,
      age 44.4 +/- 12.1 years, 75.5% female. Overall NAFLD prevalence was 74.1%, with
      17.1% having non-alcoholic steatohepatitis (NASH) and/or steatofibrosis. Odds of
      NASH/steatofibrosis increased independently with BMI category (odds ratio (OR)
      2.28-3.46, all p < 0.05) and metabolic disease (OR 3.79, p = 0.003). These odds
      markedly increased when both super obesity (BMI > 50) and metabolic disease were
      present (OR 9.71, p < 0.001). NASH/steatofibrosis prevalence was significantly
      greater with diabetes, hypertension and dyslipidemia. Although greater visceral
      adipocyte hypertrophy was evident in NASH/steatofibrosis, there was no
      significant association between adipose inflammation and NASH/steatofibrosis.
      CONCLUSION: NAFLD remains endemic in obesity; however, NASH/steatofibrosis are
      less common than previously reported. Worsening obesity and metabolic disease
      increase odds of NAFLD independently, with substantially compounded effect with
      both. These observations may help with risk stratification in obese populations.
      We were unable to delineate clear associations between adipose inflammation and
      NASH/steatofibrosis in this obese population. TRIAL REGISTRATION: Australian
      Clinical Trials Registry ( ACTRN12615000875505 ).

PMID- 30229461
TI  - Examination of the Effectiveness of a Brief, Adapted Dialectical Behavior Therapy
      Skills Training Group for Bariatric Surgical Candidates.
AB  - BACKGROUND: Bariatric surgery is the most effective treatment for morbid obesity,
      yet 20 to 30% of such patients regain weight approximately 2 years post-surgery.
      A psychological intervention adjunctive to bariatric surgery that addresses
      eating pathology often observed in bariatric populations may improve outcomes. In
      the present study, a brief, adapted DBT-ST group for bariatric surgical
      candidates was evaluated as an adjunctive intervention to bariatric surgery in
      the pre-surgical period to reduce eating pathology and clinical impairment.
      METHODS: Participants included 95 bariatric surgery candidates, with 50
      candidates in the DBT-ST plus treatment as usual (TAU) group and 45 candidates in
      the TAU (i.e., comparison) group. Participants completed measures of eating
      pathology at three time points (i.e., T1 = pre-DBT-ST program; T2 = post-DBT-ST
      program; T3 = 4 months post-DBT-ST; comparable time points employed for TAU
      group). Average wait time for surgery following the pre-surgical program was
      approximately 2 to 4 months. RESULTS: A series of 2 (group: DBT-ST + TAU versus
      TAU) * 3 (assessment time: T1, T2, and T3) mixed-model ANOVAs were completed.
      Participants in the DBT-ST plus TAU group showed significant reductions in binge
      eating, emotional eating, global eating pathology, and clinical impairment
      related to eating difficulties over time in comparison to TAU. CONCLUSIONS:
      Findings demonstrated that a brief DBT-ST group integrated as an adjunctive
      intervention to TAU in a bariatric pre-surgical program could aid in addressing
      eating pathology. Bariatric participants in a DBT-ST plus TAU group may be on a
      better weight loss trajectory than those who only receive TAU.

PMID- 30229462
TI  - Optimizing Lipid Pattern by Adding a Combined Nutraceutical or Pravastatin to
      Fenofibrate Treatment in Hypertriglyceridemic Subjects: Single Site, Randomized,
      Open-Label, Post-Market Clinical Investigation.
AB  - INTRODUCTION: Fenofibrate is an effective and safe treatment for
      hypertriglyceridemia. However, after TG reduction a residual dyslipidemia could
      appear and require further treatment. AIM: To comparatively evaluate the short
      term tolerability and efficacy of a combined lipid-lowering nutraceutical and
      pravastatin 40 mg in fenofibrate treated patients. METHOD: We prospectively
      enrolled 40 patients well-tolerating treatment with micronized fenofibrate 145
      mg/day and with residual dyslipidemia (LDL-C > 115 mg/dL and TG > 150 mg/dL).
      Exclusion criteria have been type 2 diabetes, Familial Hypercholesterolemia,
      previous cardiovascular diseases and severe chronic kidney disease. Then, we have
      randomly assigned the patients to treatment with pravastatin 40 mg or a combined
      lipid-lowering nutraceutical (Armolipid Plus(r), containing monacolin 3 mg and
      berberine 500 mg). RESULTS: After 8 weeks of treatment, 80% of pravastatin
      treated patients (N. 16/20) and 75% of those treated with Armolipid Plus(r) (N.
      15/20) reached the desired LDL-C target, while 50% of pravastatin treated
      patients (N. 10/20) and 80% of the Armolipid Plus(r) treated ones reached the
      desired TG target (N. 16/20). No one adverse event has been registered during
      Armolipid Plus(r), while 1 patient claimed myalgia and 1 reported significant
      increase of CPK (> 3 ULN) during pravastatin treatment. Both patients were then
      treated with Armolipid Plus(r) with resolution of symptoms and CPK increase,
      respectively. CONCLUSION: In hypertriglyceridemic patients treated with
      fenofibrate, the association with a combined lipid lowering nutraceutical seem to
      be more effective in optimizing residual hypertriglyceridemia than pravastatin 40
      mg, while being more tolerable and having similar effect on LDL-C plasma level.

PMID- 30229464
TI  - Correction to: Comparisons of percutaneous versus retroperitoneoscopic
      cryoablation for renal masses.
AB  - In the original publication, Prof. Lin-Nei Hsu's institution was incorrectly
      published as 'Tainan Municipal An-Nan Hospital' in affiliation 4. The correct
      affiliation should read as 'Department of Urology, An-Nan Hospital, China Medical
      University, Tainan, Taiwan'.

PMID- 30229463
TI  - What Is the Best Endoscopic Strategy in Acute Non-variceal Gastrointestinal
      Bleeding?
AB  - OPINION STATEMENT: PURPOSE OF REVIEW: Upper non-variceal gastrointestinal
      bleeding (UNVGIB) remains an important clinical challenge for endoscopists,
      requiring skill and expertise for correct management. In this paper, we suggest
      the best strategy for an effective treatment of this complex category of
      patients. RECENT FINDINGS: Early endoscopic examination, the increasingly
      widespread use of endoscopic hemostasis methods, and the most powerful
      antisecretory agents that induce clot stabilization have radically modified the
      clinical scenario for treating this pathology. While hospitalization for
      digestive hemorrhage is decreasing, the incidence of bleeding seems to be
      increasing, especially in the elderly for whom a greater use of gastrolesive
      drugs and the presence of comorbidities are more common. A multidisciplinary
      approach for initial patient evaluation and hemodynamic resuscitation prior to
      endoscopic treatment is crucial for correct management, prevention of rebleeding,
      and reduction of morbidity and mortality rates and hospital stays. Appropriate
      operator technical expertise, together with the availability of a wide range of
      endoscopes and devices, is mandatory. Newer endoscopic techniques may improve
      patient outcomes for difficult-to-treat lesions. Today, endoscopic hemostasis can
      be achieved in over 95% of patients.

PMID- 30229465
TI  - A negative multiparametric magnetic resonance imaging finding does not guarantee
      the absence of significant cancer among biopsy-proven prostate cancer patients: a
      real-life clinical experience.
AB  - PURPOSE: We analyzed the data of consecutive patients who had preoperative
      multiparametric magnetic resonance imaging (mpMRI) and underwent radical
      prostatectomy (RP) to evaluate the actual performance of mpMRI among biopsy
      proven prostate cancer (PCa) patients in predicting favorable pathology in the
      real-life clinical setting. METHODS: Among a total 730 biopsy-proven PCa patients
      underwent RP, the preoperative mpMRIs of 534 patients were positive,
      demonstrating one or more PI-RADs V2 grade >= 2 lesion(s). Other 196 mpMRIs were
      classified as negative, without any suspicious lesion. Pathology was classified
      to be unfavorable when showing Gleason score (GS) 4/5 or pT3/N1 features.
      Significant cancer was defined as non-organ-confined, GS 4/5, or cancer volume of
      >= 0.5 mL. RESULTS: Among a total 196 negative preoperative mpMRI patients, final
      RP pathology showed that 20 (10.2%) had pT3 disease and 2 (1.0%) had pN1 disease.
      Regarding the pathologic Gleason score, 117 (59.7%) had GS 3 + 4 and 44 (22.4%)
      had GS >= 4 + 3. The rate of a favorable PCa and an insignificant cancer was as
      low as 14.3% and 10.2%. Even among only the 101 D'Amico low-risk patients with
      negative MRI, the rates of a favorable pathology and an insignificant cancer were
      only 18.2% and 12.7%. The sensitivity, specificity, positive, and negative
      predictive value of mpMRI to predict a significant cancer were 74.3%, 45.5%,
      95.5%, and 10.2%, respectively. CONCLUSIONS: In the real-life clinical setting,
      mpMRI demonstrated limited performance in the prediction of favorable and
      insignificant prostate cancer as a negative mpMRI could not guarantee the absence
      of unfavorable pathology among PCa patients.

PMID- 30229466
TI  - Neoadjuvant chemohormonal therapy followed by robot-assisted and minimum incision
      endoscopic radical prostatectomy in patients with high-risk prostate cancer:
      comparison of perioperative and oncological outcomes at single institution.
AB  - PURPOSE: Optimal management strategies for patients with high-risk prostate
      cancer (PCa) have not been established. This study aimed to estimate the impact
      of surgical procedures on perioperative and oncological outcomes in patients with
      high-risk PCa who received neoadjuvant chemohormonal therapy (CHT) prior to
      radical prostatectomy (RP). METHODS: In this retrospective study, we focused on
      patients with high-risk PCa who received neoadjuvant CHT followed by RP. The
      enrolled patients were divided into the following two groups according to
      surgical procedure: the robot-assisted RP (RARP) group and minimum incision
      endoscopic RP (MIE-RP) group. The primary endpoint was biochemical recurrence
      free survival (BRFS). RESULTS: A total of 522 high-risk PCa patients were
      enrolled in this study. The median operating time was significantly shorter in
      the MIE-RP group than in the RARP group. The median estimated blood loss was
      significantly lower in the RARP group than in the MIE-RP group. The rates of
      positive surgical margins (PSMs) were not statistically significant in either
      group. During the follow-up period, biochemical recurrence (BCR) without clinical
      recurrence occurred in 60 (23.9%) patients in the MIE-RP group and 5 (1.8%) in
      the RARP group. The 5-year BRFS rate was 76.5% in the MIE-RP group and 97.6% in
      the RARP group (P < 0.001). On multivariate analysis, RARP, PSM, pathological T
      stage, and initial prostate-specific antigen were significantly associated with
      BCR. CONCLUSIONS: Neoadjuvant CHT with subsequent RARP may decrease the risk of
      BCR when compared to MIE-RP.

PMID- 30229467
TI  - A review of heavy metal cation binding to deoxyribonucleic acids for the creation
      of chemical sensors.
AB  - Various human activities lead to the pollution of ground, drinking, and
      wastewater with toxic metals. It is well known that metal ions preferentially
      bind to DNA phosphate backbones or DNA nucleobases, or both. Foreman et al.
      (Environ Toxicol Chem 30(8):1810-1818, 2011) reported the use of a DNA-dye based
      assay suitable for use as a toxicity test for potable environmental water. They
      compared the results of this test with the responses of live-organism bioassays.
      The DNA-based demonstrated that the loss of SYBR Green I fluorescence dye bound
      to calf thymus DNA was proportional to the toxicity of the water sample. However,
      this report raised questions about the mechanism that formed the basis of this
      quasi-quantitatively test. In this review, we identify the unique and preferred
      DNA-binding sites of individual metals. We show how highly sensitive and
      selective DNA-based sensors can be designed that contain multiple binding sites
      for 21 heavy metal cations that bind to DNA and change its structure, consistent
      with the release of the DNA-bound dye.

PMID- 30229469
TI  - Severe pulmonary haemorrhage syndrome in leptospirosis in a returning traveller.
AB  - Clinical presentation of leptospirosis ranges from asymptomatic infection to
      fulminant, life-threatening disease. Pulmonary involvement in terms of severe
      pulmonary haemorrhage syndrome (SPHS) has recently become a more frequently
      reported facet of leptospirosis and correlates with high mortality rates. It has
      not yet been described in returning German travellers. We present a case of a
      healthy young man developing massive pulmonary haemorrhage and severe ARDS
      requiring mechanical ventilation and high-dose catecholamines after travelling to
      Indonesia. Leptospirosis was verified by blood PCR as well as serology and
      treated with high-dose, intravenous penicillin. Outcome was favourable, the
      patient recovered completely. Leptospirosis and SPHS should be taken into account
      as an emerging infectious disease in patients with fever and lung involvement.

PMID- 30229468
TI  - Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent
      Literature.
AB  - PURPOSE OF REVIEW: To evaluate the degree to which recent studies provide
      evidence that the effects of prenatal maternal stress (PNMS) on child health
      outcomes vary depending on the child's biological sex. In this review, we used a
      broad definition of stress, including negative life events, psychological stress,
      and established stress biomarkers. We identified 50 peer-reviewed articles
      (published January 2015-December 2017) meeting the inclusion criteria. RECENT
      FINDINGS: Most articles (k = 35) found evidence of either sex-specific
      associations (significant in one sex but not the other) or significant
      PNMSxstress interactions for at least one child health outcome. Evidence for sex
      dependent effects was strongest in the group of studies evaluating child
      neural/nervous system development and temperament as outcomes. There is
      sufficient evidence of sex-dependent associations to recommend that researchers
      always consider the potential role of child sex in PNMS programming studies and
      report descriptive statistics for study outcomes stratified by child biological
      sex.

PMID- 30229470
TI  - 'Lost in Nasal Space': Staphylococcus aureus sepsis associated with Nasal
      Handkerchief Packing.
AB  - INTRODUCTION: Staphylococcus aureus frequently causes infections in outpatient
      and hospital settings and can present as a highly variable entity. Typical
      manifestations are endocarditis, osteoarticular infections or infection of
      implanted prostheses, intravascular devices or foreign bodies. A thorough
      diagnostic evaluation with early focus identification is mandatory to improve
      patient outcome. CASE REPORT: We report a case of a 68-year old patient with a
      history of double allogeneic stem cell transplant for acute myeloid leukemia who
      developed a S. aureus bacteremia with dissemination, severe sepsis and lethal
      outcome due to nasal handkerchief packing after nose bleeding. CONCLUSION: A
      thorough medical examination with further diagnostic work-up is most important in
      S. aureus blood stream infection to identify and eradicate the portal(s) of
      entry, to rule out endocarditis, to search for spinal abscesses, osteomyelitis or
      spondylodiscitis. Adherence to management guides for clinicians must be of major
      importance to achieve optimal quality of clinical care, and thus improve patient
      outcome.

PMID- 30229472
TI  - Incorporating Critical Reflection Activities into Psychiatry Education.

PMID- 30229473
TI  - Physical Therapy Approaches in the Treatment of Low Back Pain.
AB  - Globally, in 2016, low back pain (LBP) contributed 57.6 million of total years
      lived with disability. Low Back Pain Guidelines regularly recommend the use of
      physical exercise for non-specific LBP. Early non-pharmacological treatment is
      endorsed. This includes education and self-management, and the recommencement of
      normal activities and exercise, with the addition of psychological programs in
      those whose symptoms persist. The aim of physical treatments is to improve
      function and prevent disability from getting worse. There is no evidence
      available to show that one type of exercise is superior to another, and
      participation can be in a group or in an individual exercise program. Active
      strategies such as exercise are related to decreased disability. Passive methods
      (rest, medications) are associated with worsening disability, and are not
      recommended. The Danish, United States of America, and the United Kingdom
      Guidelines recommend the use of exercise on its own, or in combination with other
      non-pharmacological therapies. These include tai chi, yoga, massage, and spinal
      manipulation. Public health programs should educate the public on the prevention
      of low back pain. In chronic low back pain, the physical therapy exercise
      approach remains a first-line treatment, and should routinely be used.

PMID- 30229474
TI  - A PCR microreactor machinery with passive micropump and battery-powered heater
      for thermo-cycled amplifications of clinical-level and multiplexed DNA targets.
AB  - A self-contained polymerase chain reaction (PCR) platform with miniaturized power
      system is introduced. It is powered by portable lithium batteries and integrated
      continuous-flow PCR amplification platform. Generally speaking, traditional
      commercial thermal cyclers rely on external electric supply and thus they are too
      big in instrument size. This prevents real-timely and field testing during PCR
      diagnosis. The authors are introducing a continuous-flow 3D spiral microreactor
      for DNA amplifications and high-resolution multiplexed targets' detection by
      utilizing the polyvinyl chloride (PVC) tubing-polymer to fabricate the
      microreactor for the first time. The whole setup (that can all be placed in one
      hand) includes (a) the thermo-cycled control (5.5 cm width, 10 cm length and 11
      cm height), (b) the passive continuous-flow control, and (c) the trapezoidal PCR
      microreactor. The PCR platform can work for 4.5 h continuously. With minimal
      accessories and operations, the total cost of the self-contained PCR machinery is
      <20 $, much lower than the mainstream of commercial PCR machinery. By waiving
      external electric supply, this miniaturized PCR platform is applied to amplify
      the typical DNA fragments of plasma isolated hepatitis B virus (HBV), influenza
      virus (H7N9avian influenza) bacterium (Escherichia coli) plasmid and multiplexed
      targets. The efficiency of the method is 70% of that of commercial thermal cycler
      (CFX Connect, Bio Rad). The DNA of H7N9avian influenza can be detected in
      concentrations as low as 103 copies per MUL. Graphical abstract By utilizing the
      polyvinyl chloride (PVC) tubing-polymer to fabricate the microchip for the first
      time, this paper introduces a 3D spiral microreactor with a miniaturized power
      system supplied by portable AA-batteries, applied in DNA amplifications and high
      resolution multiplexed targets' detection. In this microdevice, we made the
      machinery portable by waiving the external plugs, which solved the problem of
      traditional commercial thermal cyclers about large volume and expensive price.

PMID- 30229475
TI  - Human leucocyte antigen (HLA)-A, -B, -C, -DRB1 and -DQB1 haplotype frequencies
      from 2491 cord blood units from Tamil speaking population from Tamil Nadu, India.
AB  - The Public Cord Blood Bank of Jeevan Stem Cell Foundation was established in 2008
      to harvest cord blood units and make them available to treat multiple blood
      disorders through Hematopoietic Stem Cell Transplants. We studied Human Leucocyte
      Antigen (HLA)-A, -B, -C, -DRB1 and -DQB1 allele and haplotype diversity in a
      sample of 2491 unrelated cord-blood units from Jeevan's Public Cord Blood Bank
      (part of Be The Cure Registry) in the Tamil Nadu state in the Indian Peninsula.

PMID- 30229471
TI  - Targeting Toll-Like Receptors for Cancer Therapy.
AB  - The immune system encompasses a broad array of defense mechanisms against foreign
      threats, including invading pathogens and transformed neoplastic cells. Toll-like
      receptors (TLRs) are critically involved in innate immunity, serving as pattern
      recognition receptors whose stimulation leads to additional innate and adaptive
      immune responses. Malignant cells exploit the natural immunomodulatory functions
      of TLRs, expressed mainly by infiltrating immune cells but also aberrantly by
      tumor cells, to foster their survival, invasion, and evasion of anti-tumor immune
      responses. An extensive body of research has demonstrated context-specific roles
      for TLR activation in different malignancies, promoting disease progression in
      certain instances while limiting cancer growth in others. Despite these
      conflicting roles, TLR agonists have established therapeutic benefits as anti
      cancer agents that activate immune cells in the tumor microenvironment and
      facilitate the expression of cytokines that allow for infiltration of anti-tumor
      lymphocytes and the suppression of oncogenic signaling pathways. This review
      focuses on the clinical application of TLR agonists for cancer treatment. We also
      highlight agents that are undergoing development in clinical trials, including
      investigations of TLR agonists in combination with other immunotherapies.

PMID- 30229476
TI  - Left ventricular remodeling after the first myocardial infarction in association
      with LGALS-3 neighbouring variants rs2274273 and rs17128183 and its relative mRNA
      expression: a prospective study.
AB  - Post-infarct left ventricular remodeling (LVR) process increases the risk of
      heart failure (HF). Circulating galectin-3 has been associated with fibrosis,
      inflammation and cardiac dysfunction during the remodeling process after
      myocardial infarction (MI). The aims of this prospective case study were to
      investigate the association of potentially functional variants in the vicinity of
      LGALS-3 locus, rs2274273 and rs17128183 with maladaptive LVR and whether these
      variants could affect LGALS-3 mRNA expression in peripheral blood mononuclear
      cells of patients 6 months after the first MI. This study encompassed 167
      patients with acute MI that were followed up for 6 months. Evidence of LVR was
      obtained by repeated 2D Doppler echocardiography. Rs2274273, rs17128183 and LGALS
      3 mRNA expression were detected by TaqMan(r) technology. Rs2274273 and rs17128183
      rare allele bearing genotypes, according to the dominant model (CT+TT vs. CC and
      AG+GG vs. AA, respectively), were significantly and independently associated with
      maladaptive LVR (adjusted OR = 3.02, P = 0.016; adjusted OR = 3.14, P = 0.019,
      respectively) and higher LGALS-3 mRNA expression (fold induction 1.203, P = 0.03
      and 1.214, P = 0.03, respectively). Our exploratory results suggest that
      rs2274273 and rs17128183 variants affect LGALS-3 mRNA and bear the risk for
      maladaptive LVR post-MI remodeling. Further replication and validation in a
      larger group of patients is inevitable.

PMID- 30229478
TI  - Confidence carryover during interleaved memory and perception judgments.
AB  - Recognition memory tests typically consist of randomly intermixed studied and
      nonstudied items that subjects classify as old or new, often while indicating
      their confidence in these classifications. Under most decision theories,
      confidence ratings index an item's memory strength-the extent to which it elicits
      evidence of prior occurrence. Because the test probes are randomly ordered, these
      theories predict that confidence judgments should be sequentially independent:
      confidence on trial n should not predict confidence on n + 1. However, analysis
      of two extant data sets demonstrated reliable serial correlations in recognition
      memory confidence (confidence carryover). In a new experiment, we examined the
      domain specificity of confidence carryover by serially interleaving recognition
      and perceptual classification judgments. Analysis revealed domain-general and
      domain-specific confidence carryover effects: The confidence of a current
      recognition judgment was shown to reflect both the confidence of an immediately
      preceding perceptual gender judgment (domain-general carryover at Lag 1) and also
      the confidence of the recognition judgment prior to that (domain-specific
      carryover at Lag 2). Moreover, the domain-specific effect was sensitive to
      response consistency: Confidence carryover was highest when old-new
      classifications repeated across trials. Whereas the domain-general effect may
      reflect metacognitive monitoring of internal factors such as alertness, the
      domain-specific effect was easily simulated by assuming that evidence within
      domains is "sticky," such that current memory or perceptual evidence is pulled
      toward prior evidence representations.

PMID- 30229477
TI  - The role of circulating tumor cells in metastatic breast cancer: prognostic and
      predictive value.
AB  - The aim of the current study was to assess the prognostic value of circulating
      tumor cells (CTCs) and their related markers at different points of chemotherapy
      regimens in metastatic breast cancer (MBC) patients. The impact of CTCs on
      progression free survival (PFS) and overall survival (OS) rates were also
      assessed. Peripheral blood samples were obtained from 66 female patients with MBC
      at different time intervals for evaluation of CTCs by flow cytometry (FC).
      cytokeratin 19 (CK19), mammaglobin, prolactin inducible peptide (PIP), aldehyde
      dehydrogenase 1 (ALDH1) and human chorionic gonadotropin (hCG) were also assessed
      by qRT-PCR. Analysis of different CTC levels (at 4, 5, and 6 cells/7 ml), showed
      statistically significant values at 4 cells/7 ml blood. The presence of baseline
      CTCs < 4 cells/7 ml, associated significantly with higher PFS (P value = 0.03).
      Patients showing a decrease in the CTCs level after treatment had significantly
      prolonged median PFS and OS rates compared to those whose CTCs level increased (P
      = 0.007 and P = 0.014; respectively). Mammaglobin, CK19, PIP, ALDH1 and hCG
      expression did not affect PFS or OS. However, patients with CTCs >= 4 at
      diagnosis had higher rates of progression compared to those with CTCs < 4 (1.9
      times, P = 0.07), and who metastasized before 4 years showed a worse decrease
      outcomes (they were 2.4 time more progressed than those who metastasized after 4
      years; P = 0.029). CTCs could be an independent prognostic and predictive
      biomarker for MBC patients' outcomes. Although none of the assessed genes
      (mammaglobin, CK19, PIP, ALDH1 and hCG) showed correlation with PFS or OS rates,
      further studies on a larger number of patients are required to validate the
      current results.

PMID- 30229479
TI  - Event memory uniquely predicts memory for large-scale space.
AB  - When a person explores a new environment, they begin to construct a spatial
      representation of it. Doing so is important for navigating and remaining
      oriented. How does one's ability to learn a new environment relate to one's
      ability to remember experiences in that environment? Here, 208 adults experienced
      a first-person videotaped route, and then completed a spatial map construction
      task. They also took tests of general cognitive abilities (working memory,
      laboratory episodic memory, processing speed, general knowledge) and of memory
      for familiar, everyday activities (event memory). Regression analyses revealed
      that event memory (memory for everyday events and their temporal structure),
      laboratory episodic memory (memory for words and pictures) and gender were unique
      predictors of spatial memory. These results implicate the processing of temporal
      structure and organization as an important cognitive ability in large-scale
      spatial-memory-from-route experience. Accounting for the temporal structure of
      people's experience while learning the layout of novel spaces may improve
      interventions for addressing navigation problems.

PMID- 30229480
TI  - Building Toward a Population-Based Approach to Diabetes Screening and Prevention
      for US Adults.
AB  - PURPOSE OF REVIEW: Evidence-based treatments for prediabetes can prevent and
      delay the development of type 2 diabetes in adults. In this review, we propose a
      framework for population-based diabetes prevention that links screening and
      prevention activities across key stakeholders. We also discuss gaps in current
      practice, while highlighting opportunities to improve diabetes screening and
      prevention efforts population-wide. RECENT FINDINGS: Awareness of diabetes risk
      is low, and many adults with prediabetes are not identified through existing
      screening efforts. Accumulating evidence and policies support expansion of the
      Diabetes Prevention Program (DPP) into clinical and community settings. However,
      the infrastructure to facilitate referrals and promote data exchange among
      patients, clinical settings, and community-based DPP programs is lacking.
      Development of evidence-driven, scalable processes for assessing diabetes risk,
      screening eligible adults, and delivering preventive treatments are needed to
      effectively improve the glycemic health of the US adult population.

PMID- 30229482
TI  - Lipids: a personal view of the past decade.
AB  - The past decade has witnessed considerable progress in the field of lipids. New
      drugs have been "rapidly" developed and some of these drugs have already been
      evaluated in event-based large trials. This evidence has led to the guidelines
      recommending new, more aggressive treatment goals for low-density lipoprotein
      cholesterol (LDL-C) levels. Although LDL-C remains the principal goal for
      cardiovascular disease (CVD) risk reduction, there has also been considerable
      interest in other lipid variables, such as high-density lipoprotein cholesterol,
      triglycerides, and lipoprotein(a). Statin intolerance is now considered a very
      important topic in daily clinical practice. This has resulted in more attention
      focusing on non-statin drugs [e.g., ezetimibe and proprotein convertase
      subtilisin/kexin 9 (PCSK9) inhibitors] and statin-related side effects. The
      latter mainly involve muscles, but there is also a need to consider other adverse
      effects associated with statin use (e.g., new onset diabetes). New specific areas
      of statin use have attracted interest. For example, statin-loading before
      procedures (e.g., coronary stenting), the prevention of stroke, and the treatment
      of non-alcoholic fatty liver disease (NAFLD). Statins will remain the most widely
      used drugs to treat dyslipidaemia and decrease CVD risk. However, we also need to
      briefly consider some other lipid-lowering drugs, including those that may become
      available in the future.

PMID- 30229481
TI  - Further data corroborating a pituitary contribution to the genesis of the
      Cyclopean myth.

PMID- 30229483
TI  - Assisted phytostabilisation of As, Pb and Sb-contaminated Technosols with mineral
      and organic amendments using Douglas fir (Pseudotsuga menziesii (Mirb.) Franco).
AB  - Phytoremediation of metal(loid)s by conifers is not widely studied, although
      conifers may be interesting, particularly in temperate-cold areas and/or on
      acidic soils. In this study, seeds of Douglas fir were sown in greenhouse and
      cultivated for 3 months on two Technosols highly contaminated with different
      concentrations of Pb, As and Sb and collected in two French old former mines
      located in massif Central or close to it: a mine of gold at La Petite Faye and a
      mine of lead and silver at Pontgibaud. Two amendments, a nutrient solution (NS)
      and composted sewage sludge (CSS), were tested in order to stimulate Douglas fir
      growth and to reduce the metal(loid)s mobility and phytoavailability. The
      speciation determined by sequential extractions as well as mineralogy highlight
      different geochemical behaviours of Pb, As and Sb as a function of the Technosol.
      In all cases, CSS amendments significantly reduced Pb phytoavailability as well
      as the uptake and translocation of Pb and As. Moreover, CSS stimulated the growth
      of Douglas firs highlighting that this amendment could be a good strategy for a
      better phytostabilisation of these metal(loid)s.

PMID- 30229485
TI  - Residues of endosulfan in cotton growing area of Vehari, Pakistan: an assessment
      of knowledge and awareness of pesticide use and health risks.
AB  - This study is based on self-reported information collected from selected farmers
      of Vehari District, Punjab, Pakistan, to determine their technical knowledge and
      awareness about pesticide use and associated environmental and health risks.
      Moreover, soil contamination by routinely used persistent organochlorine
      pesticide, endosulfan, was also evaluated. Survey data revealed very low literacy
      rate (on an average 9th grade education) and technical knowledge (almost missing)
      of the farmers in Vehari District. The farmers are unable to fully read and
      understand the instructions about the use of pesticide marked on the containers.
      They are not fully aware of pesticide persistence and toxicity (73%), unable to
      identify cotton pests and diseases (86%), and do not know which crop to grow in
      cotton adjacent fields (100%). Data also revealed that the farmers (100%) do not
      follow safety measure during pesticide application and are unaware of pesticide
      toxicity symptoms in human as well as the basic first-aid practices (89%).Poor
      literacy rate and lack of technical knowledge of farmers in Vehari regarding
      pesticide use and handling are posing serious environmental and health risks
      among the local inhabitants, particularly among farmers. Soil analysis results
      showed that concentration of alpha- and beta-endosulfan ranged from 0-14 to 0
      14.64 MUg/mg, respectively. Principal component analysis showed that soil organic
      matter is the key soil parameter controlling the occurrence and fate of
      endosulfan under sandy loam soil conditions of Vehari District. There is a
      serious need of improving technical and environmental knowledge of farmer about
      pesticide risks on human health in the studied area, in particular, and the
      entire country in general. Findings are of great use for policymaking in Pakistan
      to minimize pesticide risks in Pakistan.

PMID- 30229484
TI  - Probiotics and plant-derived compounds as eco-friendly agents to inhibit
      microbial toxins in poultry feed: a comprehensive review.
AB  - Some of pathogenic bacteria and fungi have the ability to produce fetal toxins
      which may be the direct causes of cytotoxicity or cellular dysfunction in the
      colonization site. Biological and non-biological environmental factors, challenge
      and microbes influence the effect of toxins on these pathogens. Modern research
      mentions that many natural materials can reduce the production of toxins in
      pathogenic microbes. However, researches that explain the mechanical theories of
      their effects are meager. This review aimed to discuss the ameliorative potential
      role of plant-derived compounds and probiotics to reduce the toxin production of
      food-borne microbes either in poultry bodies or poultry feedstuff. Moreover,
      studies that highlight their own toxicological mechanisms have been discussed.
      Adding natural additives to feed has a clear positive effect on the enzymatic and
      microbiological appearance of the small intestine without any adverse effect on
      the liver. Studies in this respect were proposed to clarify the effects of these
      natural additives for feed. In conclusion, it could be suggested that the
      incorporation of probiotics, herbal extracts, and herbs in the poultry diets has
      some beneficial effects on productive performance, without a positive impact on
      economic efficiency. In addition, the use of these natural additives in feed has
      a useful impact on the microbiological appearance of the small intestine and do
      not have any adverse impacts on intestinal absorption or liver activity as
      evidenced by histological examination.

PMID- 30229486
TI  - Adsorption and removal of chromium (VI) contained in aqueous solutions using a
      chitosan-based hydrogel.
AB  - The aim of this work was to study the adsorption and removal of chromium (VI)
      ions contained in aqueous solutions using a chitosan-based hydrogel synthesized
      via chemical crosslinking of radical chitosan, polyacrylic acid, and N,N'
      methylenebisacrylamide. Fourier-transform infrared spectroscopy confirmed the
      hydrogel synthesis and presence of reactive functional groups for the adsorption
      of chromium (VI) ions. The chromium (VI) adsorption mechanism was evaluated using
      non-linear Langmuir, Freundlich, Redlich-Peterson, and Sips isotherms, with the
      best fit found by the non-linear Redlich-Peterson isotherm. The maximum chromium
      (VI) adsorption capacities of the chitosan-based hydrogel were 73.14 and 93.03 mg
      metal per g dried hydrogel, according to the non-linear Langmuir and Sips
      isotherm models, respectively. The best kinetic fit was found with the pseudo-nth
      order kinetic model. The chromium (VI) removal percentage at pH 4.5 and 100 mg L
      1 initial metal concentration was 94.72%. The results obtained in this
      contribution can be useful for future works involving scale-up of a water and
      wastewater treatment method from a pilot plant to full-scale plant.

PMID- 30229488
TI  - A kinetic study for the Fenton and photo-Fenton paracetamol degradation in an
      annular photoreactor.
AB  - A kinetic model describing Fenton and photo-Fenton degradation of paracetamol
      (PCT) and consumption of hydrogen peroxide (H2O2) was proposed. A set of Fenton
      and photo-Fenton experiments (18 runs in total) was performed by fixing the
      initial concentration of PCT to 40 mg L-1 and varying the initial concentrations
      of H2O2 and ferrous ion, Fe2+. The experimental set-up was a well-stirred annular
      photoreactor equipped with an actinic BL TL-DK 36 W/10 1SL lamp. Experimental
      results highlighted that PCT is no more detected by HPLC analysis within a
      minimum reaction time of 2.5 and a maximum reaction time of 15.0 min. Besides, a
      maximum conversion of total organic carbon (TOC) of 68.5% was observed after 75
      min of reaction in case of using UV radiation and the highest concentrations of
      the Fenton reagents. The experimental data were used to fit the kinetic model.
      The radiation field inside the reactor was taken into account through the local
      volumetric rate of photon absorption, evaluated by assuming a line source model
      with spherical and isotropic emission. The kinetic parameters were estimated by
      using a non-linear least-squares regression procedure and root mean square errors
      (RMSE) were calculated in order to validate the feasibility of the proposed
      model. A good agreement between experimental and predicted data was observed and
      the lowest values of RMSE resulted in 5.84 and 9.59% for PCT and H2O2 normalized
      concentrations, respectively.

PMID- 30229487
TI  - Toxicity of linear alkylbenzene sulfonate to aquatic plant Potamogeton
      perfoliatus L.
AB  - Aquatic plants play an important role in maintaining the health of water
      environment in nature. Studies have shown that linear alkylbenzene sulfonate
      (LAS), a type of omnipresent pollutant, can cause toxic damage to aquatic plants.
      In the present research, we studied the physiological and growth response of
      submerged plant Potamogeton perfoliatus L. to different concentrations of LAS
      (0.1, 1.0, 10.0, 20.0, and 50.0 mg l-1). The results showed that LAS is toxic to
      P. perfoliatus, and the toxicity is dose-dependent. Only slightly reversible
      oxidative damages were observed in the physiological parameters of P. perfoliatus
      when P. perfoliatus was exposed to lower LAS doses (< 10 mg l-1): soluble sugar,
      soluble protein, H2O2, and malondialdehyde (MDA) content in P. perfoliatus
      increased significantly at 0.1 mg l-1 and then returned to normal levels at 1.0
      mg l-1. Antioxidant enzymes were activated before the LAS concentration reached
      10 mg l-1, and the activities of superoxide dismutase (SOD), catalase (CAT), and
      photosynthesis pigment content declined significantly when the concentration of
      LAS exceeded 10 mg l-1. In addition, at higher concentrations (20-50 mg l-1) of
      LAS, dry weight and fresh weight of P. perfoliatus showed significant declines.
      The results indicate that LAS above 10 mg l-1 can cause serious physiological and
      growth damage to P. perfoliatus.

PMID- 30229489
TI  - Utilization of high FFA landfill waste (leachates) as a feedstock for sustainable
      biodiesel production: its characterization and engine performance evaluation.
AB  - In present study, biodiesel was produced from landfill waste-derived oil by
      chemical transesterification process, to evaluate its potential as a renewable
      energy source for the first time. The free fatty acid percentage (FFA) in
      landfill waste oil is considered to be high, which was reduced by treating it
      with two different acids as catalyst, muriatic acid and phosphoric acid, in order
      to build a comparison between fatty acid methyl ester (FAME) contents. Further,
      it was treated with a base catalyst potassium hydroxide (KOH) to produce the
      final product. The FAME value of landfill oil when treated with muriatic acid was
      found to be 92.59%. The quality of biodiesel produced was analyzed by gas
      chromatography (GC), which indicated above 25.7% of conversion of oil into
      biodiesel when muriatic acid was used as a catalyst. The properties of the
      produced biodiesel were found to be in good agreement with ASTM D 6751 and EN
      14214 standards. Various test fuels were prepared for the engine test by blending
      10%, 20%, and 100% of landfill waste biodiesel in diesel on volumetric basis and
      designated as B10, B20, and B100, respectively. The brake thermal efficiency
      (BTE) of the engine was more while the exhaust emission was less except NOx with
      biodiesel and its blend (B10 and B20). Thus, landfill waste is a potential source
      of biodiesel, and blends of landfill waste up to 20% can be used for realizing
      better performance from the engine.

PMID- 30229490
TI  - Assessment of heavy metal in coal gangue: distribution, leaching characteristic
      and potential ecological risk.
AB  - In the process of excavation and utilization of the coal gangue hill, gangue at
      different weathering degree was exposed to the environment, which can be harmful
      to the surroundings. In order to find the law of heavy metal release and to
      evaluate the potential ecological risk, five kinds of coal gangue at different
      weathering degrees were collected from a coal mine named Suncun, an over 100-year
      old mine of Xinwen coal mining field located in Tai'an city, Shandong Province of
      China. Samples were processed with microwave digestion for total content
      determination of heavy metals, and another part of samples was processed by
      Tessier sequential extraction for chemical forms analysis. Leaching tests at
      various pH were carried out to investigate the release of heavy metal. The laws
      of transformation and release of heavy metals were discussed and potential
      ecological risk was evaluated. The results indicated that the weathering degree
      had a significant impact on the content of heavy metal. Exchangeable and
      carbonate fractions of Cr and Pb were a large proportion of the total and should
      attract great attention. Potential ecological risk was at strong level (light
      black) and was up to very strong level (deep black) because of Cd. But Cr had
      contributed the most for gray gangue, which was 71% of the total. The species of
      heavy metal in gangue changed due to weathering and lead to the difference of the
      leaching characteristic and risk.

PMID- 30229492
TI  - Unsubstituted metallophthalocyanine catalysts for the removal of endocrine
      disrupting compounds using H2O2 as oxidant.
AB  - Advanced oxidation processes have become increasingly important to treat non
      biodegradable compounds entering environmental waters. In recent decades, water
      soluble metallophthalocyanines have been shown to catalyse H2O2-containing
      oxidation reactions through the production of unique reactive species,
      nucleophilic metal-peroxo complexes. Few reports in the literature have examined
      water insoluble metallophthalocyanines (MPc). The oxidative catalytic activity of
      water insoluble manganese- and iron-phthalocyanine (MnPc, FePc) at pH 7 has been
      shown through the decolourisation of methylene blue and removal of bisphenol A.
      These studies expand on this previous study, exploring the catalytic activity of
      a range of metallophthalocyanines catalysts under both acidic and neutral
      conditions. FePc, while only active under neutral conditions, was the best
      performing catalyst. This activity was significantly improved upon by the
      addition of acetonitrile as a co-solvent, as well as increasing the ratio of H2O2
      to catalyst. MnPc was catalytically active at both pH 3 and 7. FePc and MnPc
      catalysts showed the ability to remove bisphenol A in the presence of dam water.
      Reaction rates were reduced for bisphenol A removal with FePc as a catalyst but
      were unchanged in the presence of MnPc. The removal of 17beta-estradiol, estrone,
      and coumestrol was successfully demonstrated, with greater than 96% removal of
      all tested EDC's achieved. This is the first reported study showing the removal
      of the phytoestrogen, coumestrol. Even though considerably lower concentrations
      of costly catalysts and oxidation reagents were used in our work, the removal
      extent of EDC's by the MPc-catalysed oxidation reactions achieved here compares
      favourably with literature.

PMID- 30229491
TI  - Chemical characteristics, source apportionment, and regional transport of marine
      fine particles toward offshore islands near the coastline of northwestern Taiwan
      Strait.
AB  - This study aims to investigate the spatiotemporal variation, chemical
      composition, and source apportionment of marine fine particles (PM2.5) as well as
      their regional transport toward the Matsu Islands located near the coastline of
      northwestern Taiwan Strait. Four offshore island sites located at the Matsu
      Islands were selected to conduct both regular and intensive sampling of marine
      PM2.5. Water-soluble ionic species, metallic elements, and carbonaceous contents
      were then analyzed to characterize the chemical characteristics of marine PM2.5.
      In order to identify the potential sources and their contributions to marine
      PM2.5, chemical mass balance (CMB) receptor model was employed along with the
      backward trajectory simulation to resolve the source apportionment of marine
      PM2.5 and to explore their transport routes in different seasons. The results
      showed that high PM2.5 concentrations were commonly observed during the
      northeastern monsoon periods. Additionally, marine PM2.5 concentration decreased
      from the west to the east with the highest PM2.5 at the Nankang Island and the
      lowest PM2.5 at the Donyin Island in all seasons, indicating an obvious
      concentration gradient of PM2.5 transported from the continental areas to the
      offshore islands. In terms of chemical characteristics of PM2.5, the most
      abundant water-soluble ions of PM2.5 were secondary inorganic aerosols (SO42-,
      NO3-, and NH4+) which accounted for 55-81% of water-soluble ions and 29-52% of
      marine PM2.5. The neutralization ratios of PM2.5 were always less than unity,
      indicating that NH4+ cannot solely neutralize nss-SO42+ and NO3- in marine PM2.5
      at the Matsu Islands. Although crustal elements (Al, Ca, Fe, K, and Mg) dominated
      the metallic content of marine PM2.5, trace anthropogenic metals (Cd, As, Ni, and
      Cr) increased significantly during the northeastern monsoon periods, particularly
      in winter. Organic carbons (OCs) were always higher than elemental carbons (ECs),
      and the mass ratios of OC and EC were generally higher than 2.2 in all seasons,
      implying that PM2.5 was likely to be aged particles. During the poor air quality
      periods, major air mass transport routes were the northern transport and the anti
      cyclonic circulation routes. Source apportionment results indicated that fugitive
      soil dusts and secondary aerosols were the major sources of marine PM2.5 at the
      Matsu Islands, while, in winter, biomass burning contributed up to 15% of marine
      PM2.5. This study revealed that cross-boundary transport accounted for 66~84% of
      PM2.5 at the Matsu Islands, suggesting that marine PM2.5 at the Matsu Islands has
      been highly influenced by anthropogenic emissions from neighboring Fuzhou City as
      well as long-range transport from Northeast Asia.

PMID- 30229493
TI  - Screening indices for cadmium-contaminated soil using earthworm as bioindicator.
AB  - Artificial soil simulation tests were conducted to study the response of
      oxidative stress in different parts of Eisenia fetida under cadmium Cd) stress.
      Factor analysis and analytic hierarchy process were used to establish a
      comprehensive mathematical model to screen key monitoring indices of the Cd
      contaminated soil early warning system. This paper sets the short-term group and
      the long-term group. The former lasted 10 days, and the latter was 30 days.
      Gradient solution of 0, 50, 100, 125, 250, and 500 mg kg-1 Cd2+ was used in each
      test group. The earthworm was cut into two parts from its clitellum to determine
      oxidative stress indices. Results showed that during the short-term stress, TP
      (total protein) in the head tissues of the earthworm was the key monitoring index
      for 3-4 and 8-9 days of Cd stress. In addition, the TP in tail tissues was the
      key index for 2, 4, 6, and 8-10 days of stress. On the first and second days, the
      key monitoring indices in the tail tissues were both the CAT (catalase), while in
      the head, they were CAT and TP, respectively. On the 5th, the 7th, and the 9th
      days, the focus should be on monitoring POD (peroxidase) in the tail tissues,
      while in the head tissues, they were POD, CAT, and TP, respectively. In the long
      term test after 10 days of Cd stress, the key monitoring index in head tissues
      was GPX (glutathione peroxidase), and in the tail, it was TP. At 20-30 days, the
      key monitoring indices were TP in the head and MDA (malondialdehyde) in the tail.

PMID- 30229494
TI  - In vitro assessment of the toxicity of small silver nanoparticles and silver ions
      to the red blood cells.
AB  - This work reports the toxicity of small silver nanoparticles (nanoAg, 20 nm) and
      silver ions (Ag+) to the red blood cells with the silver concentration level of
      10-6 g/mL. Results show that red blood cells (RBCs) start hemolysis when treated
      by nanoAg of 1.5 * 10-5 g/mL or Ag+ of 2.9 * 10-7 g/mL. A low ATPase activity of
      30% has been observed after RBCs being treated with Ag+ of 2.6 * 10-7 g/mL, while
      the nanoAg does not obviously affect the ATPase activity. In molecular level, Ag+
      is more toxic to the amino acid residues than nanoAg according to the change of
      fluorescence characteristics of hemoglobin (Hb). However, the nanoAg has been
      found to be more toxic than Ag+ to the secondary structure of Hb in terms of the
      loss of alpha-helix content.

PMID- 30229495
TI  - A revisit of the environmental Kuznets curve hypothesis for Turkey: new evidence
      from bootstrap rolling window causality.
AB  - This study aims at analyzing the Environmental Kuznets Curve (EKC) hypothesis for
      Turkey, spanning the period of 1961-2013. Unlike previous studies, instead of
      carbon emissions, the ecological footprint is used as a proxy for environmental
      degradation. Moreover, a bootstrap time-varying causality approach is used to
      detect the possible changes in causal relations and to obtain the parameters
      across subsample periods. The results clearly indicate that there are feedback
      relationships between economic growth and the ecological footprint in some
      subsample periods. In addition, the impact of economic growth on environmental
      degradation is positive and has a slowly increasing trend in all subsample
      periods. Therefore, the EKC hypothesis is not confirmed for the Turkish economy.
      Based on these results, some crucial policy implications are suggested.

PMID- 30229496
TI  - A Bayesian modeling approach for phosphorus load apportionment in a reservoir
      with high water transfer disturbance.
AB  - Phosphorus loading from external and internal sources poses a potential risk to
      eutrophication of lakes or reservoirs. However, the relative contribution of
      external and internal sources to eutrophication is still unclear especially for
      reservoirs with water transfer disturbance. The objective of this paper is to
      estimate the phosphorus loading from external (water transfer and diffusing
      emission) and internal sources (sediment release) in Yuqiao Reservoir (YQR) and
      compare their relative contribution of external and internal sources. In this
      study, we estimated the phosphorus loading considering both external (water
      transfer and diffusing source emission) and internal (release from sediment)
      sources of YQR. The phosphorus loading from water transfer was estimated by total
      phosphorus (TP) concentration * monthly flow of inflow. The phosphorus loading
      from nonpoint source emission was estimated using a generalized watershed loading
      function (GWLF). The phosphorus loading from internal sources was estimated with
      a Bayesian phosphorus budget model. Our result showed that water transfer TP load
      is the biggest (45.2%) source of TP load in YQR and internal TP load (20.5%)
      accounts for a comparable proportion of TP load as nonpoint source (34.3%) in YQR
      and dominates the total loading in some months. Analysis of seasonal total
      phosphorus load apportionment indicated that water transfer TP load takes the
      largest proportion in winter (60.8%), spring (60.2%), and autumn (47.8%).
      Nonpoint source TP load takes the largest proportion in summer (60.1%), and
      internal TP load is the second source of YQR in summer (22.4%). Our study
      indicates that water transfer may be the major driver of eutrophication for some
      reservoir systems, and sediment release may prevent recovery of many eutrophic
      lakes and reservoirs. Our analysis suggests that TP pollution control strategies
      in YQR should be preferentially focused on the improvement of water quality in
      the upstream reservoir, and nonpoint source TP load reductions should be focused
      on summer. Compared with conventional nutrient apportionment model applications,
      this paper provides a new approach to estimate external and internal TP loads
      simultaneously. Graphical abstract ?.

PMID- 30229497
TI  - Drosophila melanogaster as model organism for monitoring and analyzing
      genotoxicity associated with city air pollution.
AB  - This study evaluated the genotoxic potential of atmospheric pollution associated
      with urbanization using the model organism Drosophila melanogaster and the Comet
      assay with hemolymph cells. Larvae were exposed to atmospheric compounds in an
      urban and a rural area in the municipality of Vitoria de Santo Antao, Pernambuco,
      Brazil, for 6 days (from the embryo stage to the third larval stage) in April
      2015 and April 2017. The results were compared to a negative environmental
      control group exposed to a preserved area (Catimbau National Park) and to a
      negative control exposed to the laboratory room conditions. The Comet assay
      demonstrated significant genetic damage in the organisms exposed to the urban
      area compared with those exposed to the rural area and negative control groups.
      The evidences were supported by particulate matter analysis showing higher
      photopeaks of chemical elements such as aluminum, silicon, sulfur, potassium,
      calcium, titanium, and iron, associated to road dust fraction in urban
      environment. Once again, the results confirm D. melanogaster an ideal
      bioindicator organism to monitor genotoxic hazard associated with atmospheric
      pollution.

PMID- 30229499
TI  - Clinico-radiologic features and management of hematological tumors in the breast:
      a case series.
AB  - Hematological tumors arising in the breast are uncommon and require different
      treatment modalities dependent upon tumor type. Current treatment options include
      surgical excision, chemotherapy, and radiotherapy. Management of these breast
      malignancies are poorly outlined in the literature. The purpose of this case
      series is to report five cases consisting of extranodal marginal zone lymphoma,
      lymphoplasmacytic lymphoma, and extramedullary plasmacytoma occurring in the
      breast. The cases illustrate heterogeneous radiologic findings and varying
      management approaches to these tumors. The case series underscores the importance
      of having a wide differential at diagnosis and recognizes management of disease
      should be taken on an individual basis with consideration of prognosis and first
      line treatment options.

PMID- 30229500
TI  - A Non-Invasive Material Characterization Framework for Bioprosthetic Heart
      Valves.
AB  - Computational modeling and simulation has become more common in design and
      development of bioprosthetic heart valves. To have a reliable computational
      model, considering accurate mechanical properties of biological soft tissue is
      one of the most important steps. The goal of this study was to present a non
      invasive material characterization framework to determine mechanical propertied
      of soft tissue employed in bioprosthetic heart valves. Using integrated
      experimental methods (i.e., digital image correlation measurements and
      hemodynamic testing in a pulse duplicator system) and numerical methods (i.e.,
      finite element modeling and optimization), three-dimensional anisotropic
      mechanical properties of leaflets used in two commercially available
      transcatheter aortic valves (i.e., Edwards SAPIEN 3 and Medtronic CoreValve) were
      characterized and compared to that of a commonly used and well-examined surgical
      bioprosthesis (i.e., Carpentier-Edwards PERIMOUNT Magna aortic heart valve). The
      results of the simulations showed that the highest stress value during one
      cardiac cycle was at the peak of systole in the three bioprostheses. In addition,
      in the diastole, the peak of maximum in-plane principal stress was 0.98, 0.96,
      and 2.95 MPa for the PERIMOUNT Magna, CoreValve, and SAPIEN 3, respectively.
      Considering leaflet stress distributions, there might be a difference in the long
      term durability of different TAV models.

PMID- 30229498
TI  - Novel preclinical murine model of trauma-induced elbow stiffness.
AB  - BACKGROUND: Peri-articular injury may result in functional deficits and pain. In
      particular, post-traumatic elbow stiffness is a debilitating condition,
      precluding patients from performing activities of daily living. As such,
      clinicians and basic scientists alike, aim to develop novel therapeutic
      interventions to prevent and treat elbow stiffness; thereby reducing patient
      morbidity. Yet, there is a paucity of pre-clinical models of peri-articular
      stiffness, especially of the upper extremity, necessary to develop and test the
      efficacy of therapeutics. We set out to develop a pre-clinical murine model of
      elbow stiffness, resulting from soft tissue injury, with features characteristic
      of pathology observed in these patients. METHODS: A soft tissue peri-elbow injury
      was inflicted in mice using cardiotoxin. Pathologic tissue repair was induced by
      creating an investigator-imposed deficiency of plasminogen, a protease essential
      for musculoskeletal tissue repair. Functional testing was conducted through
      analysis of grip strength and gait. Radiography, microcomputed tomography, and
      histological analyses were employed to quantify development of heterotopic
      ossification. RESULTS: Animals with peri-elbow soft tissues injury in conjunction
      with an investigator-imposed plasminogen deficiency, developed a significant loss
      of elbow function measured by grip strength (2.387 +/- 0.136 N vs 1.921 +/- 0.157
      N, ****, p < 0.0001) and gait analysis (35.05 +/- 2.775 mm vs 29.87 +/- 2.075 mm,
      ***, p < 0.0002). Additionally, plasminogen deficient animals developed capsule
      thickening, delayed skeletal muscle repair, fibrosis, chronic inflammation, and
      heterotopic ossification; all features characteristic of pathology observed in
      patients with trauma-induced elbow stiffness. CONCLUSION: A soft tissue injury to
      the peri-elbow soft tissue with a concomitant deficiency in plasminogen,
      instigates elbow stiffness and pathologic features similar to those observed in
      humans. This pre-clinical model is valuable for translational studies designed to
      investigate the contributions of pathologic features to elbow stiffness or as a
      high-throughput model for testing therapeutic strategies designed to prevent and
      treat trauma-induced elbow stiffness.

PMID- 30229501
TI  - "Market withdrawals" of medicines in Germany after AMNOG: a comparison of HTA
      ratings and clinical guideline recommendations.
AB  - BACKGROUND: According to the AMNOG act, the German Federal Joint Committee (G-BA)
      determines the additional benefit of new medicines as a basis for subsequent
      price negotiations. Pharmaceutical companies may withdraw their medications from
      the market at any time during the process. This analysis aims to compare
      recommendations in clinical guidelines and HTA appraisals of medicines that were
      withdrawn from the German market since the introduction of AMNOG in 2011.
      METHODS: Medications withdrawn from the German market between January 2011 and
      June 2016 following benefit assessment were categorized as opt-outs (max. 2 weeks
      after start of price negotiations) or supply terminations (during or after
      further price negotiations). Related guidelines were systematically analyzed. For
      all withdrawals, therapeutic area, additional benefit rating and recommendation
      status in relevant clinical guidelines were assessed. RESULTS: Among 139
      medications, 10 opt-outs and 12 supply terminations were identified. Twenty-one
      out of 22 withdrawn medicines (95%) received 'no additional benefit' appraisal by
      the G-BA (average 'no additional benefit' rating for all AMNOG products: 47%). Of
      the 22 medicines, 15 (68%) were recommended by at least one guideline at the time
      of benefit assessment and 18 (82%) on 1 June 2016. Heterogeneity among guidelines
      was high. Acceptance of clinical trial endpoints was different between G-BA
      appraisals and clinical guidelines. CONCLUSION: Our analysis revealed
      considerable differences across clinical guidelines as well as between clinical
      guidelines and HTA appraisals of the medicines that were withdrawn from the
      German market. Better alignment of the clinical perspective and close
      collaboration between all involved parties is required to achieve and maintain
      optimization of patient care.

PMID- 30229503
TI  - Association of GRP78 promoter polymorphisms and serum GRP78 level with risk of
      asthenozoospermia.
AB  - PURPOSE: The aim of this study was undertaken to investigate the association of
      78-kDa glucose-regulated protein (GRP78) gene promoter polymorphisms with risk of
      asthenozoospermia (AZS) men. In addition, we performed association analysis
      between GRP78 promoter mutations and serum GRP78 level in asthenozoospermia.
      METHODS: The study population comprised 400 subjects with AZS patients and 400
      healthy controls. We assessed GRP78 rs3216733, rs17840761, and rs17840762
      polymorphisms by using Snapshot SNP genotyping assays; serum GRP78 level was
      measured by enzyme-linked immunosorbent assay (ELISA). Semen quality was assessed
      by computer-assisted semen analysis. RESULTS: We found that rs3216733 was
      associated with increased risk of AZS (Gd vs. dd: adjusted OR = 1.42, 95% CI,
      1.06-1.93, P = 0.020; Gd/GG vs. dd: adjusted OR = 1.43, 95% CI, 1.08-1.91, P =
      0.013; G vs. d adjusted OR = 1.26, 95% CI, 1.03-1.56, P = 0.027). The haplotype
      analyses showed the frequency of G-C-C haplotype was significantly higher in AZS
      (P = 0.026). The percentage of progressive motility sperm was lower in the
      asthenozoospermic men with Gd and Gd/GG genotypes than dd genotype (P = 0.003).
      Moreover, the serum GRP78 levels were significantly lower in rs3216733 Gd/GG
      genotypes compared with the dd genotype (P < 0.001). CONCLUSION: Our findings
      suggest that rs3216733 Gd/GG genotypes contribute to poor sperm motility,
      probably by decreasing the level of GRP78.

PMID- 30229502
TI  - Chromosome positioning and male infertility: it comes with the territory.
AB  - The production of functional spermatozoa through spermatogenesis requires a
      spatially and temporally highly regulated gene expression pattern, which in case
      of alterations, leads to male infertility. Changes of gene expression by
      chromosome anomalies, gene variants, and epigenetic alterations have been
      described as the main genetic causes of male infertility. Recent molecular and
      cytogenetic approaches have revealed that higher order chromosome positioning is
      essential for basic genome functions, including gene expression. This review
      addresses this issue by exposing well-founded evidences which support that
      alterations on the chromosome topology in spermatogenetic cells leads to
      defective sperm function and could be considered as an additional genetic cause
      of male infertility.

PMID- 30229505
TI  - Functional outcome and complication rate after percutaneous suture of fresh
      Achilles tendon ruptures with the Dresden instrument.
AB  - BACKGROUND: The aim of this study was to evaluate the outcome of patients with a
      rupture of the Achilles tendon (ATR) treated percutaneously with the Dresden
      instrument in the hands of surgeons others than its inventors. MATERIALS AND
      METHODS: 118 patients (FU rate: 77.1%) with an acute ATR treated with the Dresden
      instrument were retrospectively evaluated. The following data were evaluated:
      pain intensity, functional limitation, Hannover score, Achilles tendon total
      rupture score (ATRS), AOFAS ankle-hindfoot score, Tegner activity score,
      complications, maximum calf circumference (MCC) on both sides, and the Matles
      test for tendon lengthening. The effect of the time point of the surgery after
      trauma was examined. RESULTS: Hannover scores and ATRSs were good; AOFAS scores
      were excellent. Almost all patients returned to sporting activities
      postoperatively, and 66.1% were able to return to their previous level. The
      Tegner activity score revealed a slight posttraumatic decrease (p = 0.009) in the
      level of physical activity overall (pre-injury: 5.37 +/- 0.15; postoperatively:
      4.77 +/- 0.15). The re-rupture rate was 2%. No sural nerve lesions and no
      infections were reported. Even after 3 years, there was still a difference in MCC
      that was correlated with inferior clinical score and AT lengthening. Patients
      treated within the first 2 days after ATR showed inferior clinical outcomes in
      terms of AOFAS score, ATRS, and functional limitations. CONCLUSIONS: Percutaneous
      ATR suture with the Dresden instrument is a safe and reliable method. Low
      complication and re-rupture rates, good clinical results, and a high rate of
      return to play support this fact. The time point of the operation may influence
      the outcome.

PMID- 30229504
TI  - Graphene Family Materials in Bone Tissue Regeneration: Perspectives and
      Challenges.
AB  - We have witnessed abundant breakthroughs in research on the bio-applications of
      graphene family materials in current years. Owing to their nanoscale size, large
      specific surface area, photoluminescence properties, and antibacterial activity,
      graphene family materials possess huge potential for bone tissue engineering,
      drug/gene delivery, and biological sensing/imaging applications. In this review,
      we retrospect recent progress and achievements in graphene research, as well as
      critically analyze and discuss the bio-safety and feasibility of various
      biomedical applications of graphene family materials for bone tissue
      regeneration.

PMID- 30229508
TI  - Spermine and oxacillin stress response on the cell wall synthesis and the global
      gene expression analysis in Methicillin-resistance Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly emerging bacteria
      causing infection, which has developed resistance to most of the beta-lactam
      antibiotics because of newly acquired low-affinity penicillin-binding protein
      (PBP2a), which can continue to build the cell wall when beta-lactams block other
      PBPs. Exogenous spermine exerts a dose-dependent inhibition effect on the growth
      of Escherichia coli, Salmonella enterica serovar, and S. aureus. Selection of an
      MRSA Mu50 derivative which harbors mutation on PBP2 gene (named as MuM) showing
      spermine resistance and which confers a complete abolishment of spermine-beta
      lactam synergy was identified. To further investigate the gene expression
      changes, a transcriptome profiling of MuM against Mu50 (wild-type) without any
      treatment, MuM and Mu50 in response to high dose spermine and Mu50 in response to
      spermine-beta-lactam synergy at 15, 30 and 60 min time points was performed.
      Functional annotation was further performed to delineate the metabolic pathways
      associated with the significant genes. A significant down-regulation in the iron
      regulatory system, potassium channel uptake and polyamine transport system with
      an up-regulation in general stress response sigB dependent operon in MuM strain
      at 15, 30 and 60 min time points with spermine treatment compared to Mu50 strain
      was observed. Analysis of spermine-dependent synergy with beta-lactams on cell
      wall synthesis revealed that it significantly reduces the degree of cross-linkage
      on cell wall with no change in trypsin digestion pattern of purified PBPs and
      without affecting PBPs expression or PBPs acylation by Bocillin. A strong
      relation between PBP2 protein and general stress sigB response, iron, potassium
      and polyamine transport systems was observed. SigB regulon should be activated on
      stress, which was not seen in some of our previous studies where it was down
      regulated in wild-type Mu50 strain with spermine stress. Here, an intriguing
      finding is made where there seems to be a correction of this abnormal response of
      no SigB induction to a significant induction by PBP2 mutation. In MuM strain, a
      significant down-regulation of KdpABC operon genes at 15, 30 and 60 min time
      points on spermine stress is seen, which seems to be absent without spermine
      treatment. Since KCL has been found to protect the cell against spermine stress
      in wild-type strain by induction of KdpABC operon, it fails to do so in MuM
      strain underlying the importance of PBP2 protein in spermine stress. Analysis of
      spermine-dependent synergy with beta-lactams on cell wall synthesis revealed that
      it significantly reduces the degree of cross-linkage on cell wall with no change
      in trypsin digestion patterns of purified PBPs and without affecting PBPs
      expression or PBPs acylation by Bocillin. Furthermore, spermine does not help in
      enhancing the binding of beta-lactams to PBPs and binding of spermine to PBPs
      does not cause conformational changes to PBPs, as tested with trypsin digestion
      patterns. Future studies on the molecular mechanism of spermine interactions with
      these systems hold great potential for the development of new therapeutics for
      MRSA infections.

PMID- 30229507
TI  - The significant impact of apigenin on different aspects of autoimmune disease.
AB  - Autoimmune diseases are among the highest diseases to diagnose and treat. The
      current "gold standard" of care for these diseases is immunosuppressive drugs
      which interfere with overall immune responses; their long-term high-dose
      treatments would expose the patient to opportunistic, life-threatening and long
      term malignant infections. Considering the side effects and toxicity of these
      drug and also the beneficial effects of herbal compounds among their consumers,
      the professional investigation on the exact mechanism of the plant's major
      element has grown much attention in the last years. Apigenin as an extracting
      compound of plants, such as parsley and celery, which has a variety of biological
      effects, such as anti-inflammatory, anti-cancer and antioxidant effects. This
      review is intended to summarize the various effects of Apigenin on several
      autoimmune diseases which have been worked on so far. The pluralization of the
      obtained results has revealed Apigenin's effects on pro-inflammatory cytokines
      such as IL-1beta, chemokines such as ICAM-1, immune cells proliferation such as T
      cells, apoptosis, and various signaling pathways. According to these preclinical
      findings, we recommend that further robust unbiased studies should be done to use
      Apigenin as a supplementary or therapeutic element in autoimmune disease.

PMID- 30229506
TI  - High preoperative plasma endothelin-1 levels are associated with increased acute
      kidney injury risk after pulmonary endarterectomy.
AB  - OBJECTIVES: The only curative treatment for chronic thromboembolic pulmonary
      hypertension (CTEPH) is pulmonary endarterectomy (PEA). PEA requires
      cardiopulmonary bypass (CPB) which is associated with a high acute kidney injury
      (AKI) risk. Circulating endothelin-1 (ET-1) levels are elevated in CTEPH, and ET
      1 plays a pivotal role in AKI. Because AKI is burdened by high morbidity and
      mortality, we aimed to evaluate the association between preoperative ET-1 and the
      risk to develop AKI in CTEPH individuals who undergo PEA. We also evaluated the
      association of AKI and ET-1 with kidney function and mortality at 1 year after
      PEA. METHODS: In 385 consecutive patients diagnosed with CTEPH who underwent PEA
      at the Foundation IRCC Policlinico San Matteo (Pavia, Italy) from January 2009 to
      April 2015, we assessed preoperative circulating ET-1 by ELISA and identified
      presence of AKI based on 2012 KDIGO criteria. RESULTS: AKI occurred in 26.5% of
      the 347 patients included in the analysis, and was independently associated with
      preoperative ET-1 (p = 0.008), body mass index (BMI) (p = 0.022), male gender (p
      = 0.005) and duration of CPB (p = 0.002). At 1-year post PEA, estimated
      glomerular filtration rate (eGFR) significantly improved in patients who did not
      develop AKI [DeltaeGFR 5.6 ml/min/1.73 m2 (95% CI 3.6-7.6), p < 0.001] but not in
      those with perioperative AKI. AKI (p < 0.001), age (p < 0.001), preoperative eGFR
      (p < 0.001) and systemic hypertension diagnosis (p = 0.015) were independently
      associated with 1-year DeltaeGFR. Neither perioperative AKI nor preoperative ET-1
      was associated with 1-year survival. CONCLUSION: Perioperative AKI is associated
      with higher preoperative circulating ET-1 and it negatively influences long-term
      kidney function in patients with CTEPH who undergo PEA.

PMID- 30229509
TI  - Hair follicles transcriptome profiles in Bashang long-tailed chickens with
      different plumage colors.
AB  - Despite the rich variety in plumage color found in nature, genetic studies on how
      hair follicles affect pigmentation are often limited to animals that have black
      and white pigment. To test how gene expression influences plumage color,
      transcriptomes of chicken hair follicles with white, black, hemp, reed catkins,
      silvery grey, and landscape plumage colors were generated using Illumina
      sequencing. We generated six RNA-Seq libraries with over 25 million paired-end
      clean reads per library with percentage of paired-end clean reads ranging from
      96.73 to 96.98%. 78% of the reads mapped to the chicken genome, and approximately
      70% of the reads were mapped to exons and 6% mapped to introns. Transcriptomes of
      hair follicles producing hemp and land plumage were similar, but these two showed
      moderate differences compared with gray and reed colored plumage. The black and
      white follicle transcriptomes were most divergent from the other colors. We
      identified several candidate genes, including GPNMB, PMEL, TYRP1, GPR143, OCA2,
      SOX10, SLC45A2, KRT75, and TYR. All of these genes are known to induce pigment
      formation in mice. White feathers result from the lack of pigment formation, and
      our results suggest that the white chickens due to the recessive insertion
      mutation of TYR. The formation of black area size and color depth may be due to
      the expression levels of GPNMB, PMEL, TYRP1, GPR143, OCA2, SOX10, SLC45A2, KRT75,
      and TYR. The GO analysis of the differentially expressed genes (DEGs) revealed
      that DEGs in our transcriptome analysis were enriched in cytoskeleton and cell
      structure related pathways. The black plumage transcriptome showed significant
      differences in melanogenesis, tyrosine metabolism, and riboflavin metabolism
      compared with transcriptomes of other plumage colors. The transcriptome profiles
      of the different chicken plumage colors provide a valuable resource to understand
      how gene expression influences plumage color, and will be an important resource
      for identifying candidate genes in breeding programs.

PMID- 30229510
TI  - Interest in, willingness-to-pay for and willingness-to-recommend genetic testing
      for prostate cancer among affected men after radical prostatectomy.
AB  - Knowledge about interest in genetic testing and willingness-to-pay for a genetic
      test among men affected from prostate cancer (PCa) is limited. This study aimed
      to gain insight into men's attitudes in genetic testing for PCa. 4699 men with
      PCa from the German multicenter prospective database "Familial Prostate Cancer"
      were included. Interest in, Willingness-to-pay for and Willingness-to-recommend a
      genetic test for PCa were quantified. Associations with several sociodemographic
      and psychosocial variables were evaluated by logistic regression. 76.8% of the
      affected men with a median follow-up of 12.9 years were interested in a genetic
      test for PCa. Newly identified variables significantly associated with interest
      were having sons (OR 1.66, p < 0.001) and a high perceived severity of the PCa
      (OR 1.40, p < 0.001). 19% of men were willing to pay more than 500 ? for a
      genetic test. Men with higher education, men with a better self-reported economic
      situation and men with a lethal PCa in their family were more likely to be
      willing to pay a larger sum for a test. 84.9% of men were willing to recommend a
      test to their relatives. Interest in genetic testing for PCa among affected men
      was generally high with most men willing to recommend a test to their relatives.
      Various characteristics associated with interest and willingness-to-pay larger
      sums for genetic testing were uncovered and need to be addressed when designing
      both future educational material and genetic tests for PCa.

PMID- 30229511
TI  - The Thioredoxin-Like Family of Selenoproteins: Implications in Aging and Age
      Related Degeneration.
AB  - The thioredoxin-like (Rdx) family proteins contain four selenoproteins
      (selenoprotein H, SELENOH; selenoprotein T, SELENOT; selenoprotein V, SELENOV;
      selenoprotein W, SELENOW) and a nonselenoprotein Rdx12. They share a CxxU or a
      CxxC (C, cysteine; x, any amino acid; U, selenocysteine) motif and a stretch of
      eGxFEI(V) sequence. From the evolutionary perspective, SELENOW and SELENOV are
      clustered together and SELENOH and SELENOT are in another branch. Selenoproteins
      in the Rdx family exhibit tissue- and organelle-specific distribution and are
      differentially influenced in response to selenium deficiency. While SELENOH is
      nucleus-exclusive, SELENOT resides mainly in endoplasmic reticulum and SELENOW in
      cytosol. SELENOV is expressed essentially only in the testes with unknown
      cellular localization. SELENOH and SELENOW are more sensitive than SELENOT and
      SELENOV to selenium deficiency. While physiological functions of the Rdx family
      of selenoproteins are not fully understand, results from animal models
      demonstrated that (1) brain-specific SELENOT knockout mice are susceptible to 1
      methyl-4-phenylpyridinium-induced Parkinson's disease in association with redox
      imbalance and (2) adult zebrafishes with heterozygous SELENOH knockout are prone
      to dimethylbenzanthracene-induced tumorigenesis together with increased DNA
      damage and oxidative stress. Further animal and human studies are needed to fully
      understand physiological roles of the Rdx family of selenoproteins in redox
      regulation, genome maintenance, aging, and age-related degeneration.

PMID- 30229512
TI  - A first-in-human phase 1a study of the bispecific anti-DLL4/anti-VEGF antibody
      navicixizumab (OMP-305B83) in patients with previously treated solid tumors.
AB  - Purpose Navicixizumab (OMP-305B83) is a bispecific antibody that inhibits delta
      like ligand 4 and vascular endothelial growth factor. This Phase 1a trial
      assessed escalating doses of navicixizumab in refractory solid tumors patients.
      Design A 3 + 3 dose escalation design was used followed by the treatment of
      additional patients in an expansion cohort. Study objectives were determination
      of the maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics,
      immunogenicity and efficacy. Results Sixty-six patients were treated once every 3
      weeks in 8 dose-escalation cohorts (0.5, 1, 2.5, 3.5, 5, 7.5, 10, and 12.5 mg/kg)
      and an expansion cohort (7.5 mg/kg). The median age was 60 years and 68% of the
      patients were female. The most commonly enrolled tumor types were ovarian (12),
      colorectal (11) and breast, pancreatic, uterine and endometrial (4 each) cancers.
      As only 1 dose limiting toxicity occurred, the maximum tolerated dose was not
      reached, but 7.5 mg/kg was chosen as the dose for the expansion cohort. The
      treatment related adverse events (>=15% of patients) were hypertension (57.6%),
      headache (28.8%), fatigue (25.8%), and pulmonary hypertension (18.2%). Pulmonary
      hypertension was mostly asymptomatic at doses <=5 mg/kg (6 Gr1, 1 Gr2), but was
      more severe at higher doses (4 Gr2, 1 Gr3). Navicixizumab's half-life was 11.4
      days and there was a moderate (29%) incidence of anti-drug antibody formation.
      Four patients (3 ovarian cancer, 1 uterine carcinosarcoma) had a partial response
      and 17 patients had stable disease. Nineteen patients had a reduction in the size
      of their target lesions including 7/11 patients with ovarian cancer. Four
      patients remained on study for >300 days and 2 of these patients were on study
      for >500 days. Conclusions Navicixizumab can be safely administered with
      manageable toxicities and these data showed preliminary signs of antitumor
      activity in multiple tumor types, but was most promising in ovarian cancer. As a
      result these data justify its continued development in combination Phase 1b
      clinical trials.

PMID- 30229513
TI  - Genome Sequencing and Analysis of Bacillus pumilus ICVB403 Isolated from Acartia
      tonsa Copepod Eggs Revealed Surfactin and Bacteriocin Production: Insights on
      Anti-Staphylococcus Activity.
AB  - Here we show that Bacillus pumilus ICVB403 recently isolated from copepod eggs is
      able to produce, after 48-72 h of growth in Landy medium, extracellular
      inhibitory compounds, which are active against Staphylococcus aureus ATCC 25923,
      methicillin-resistant S. aureus (MRSA) ATCC 43300, MRSA-S1, Staphylococcus
      epidermidis 11EMB, Staphylococcus warneri 27EMB, and Staphylococcus hominis
      13EMB. Moreover, these extracellular inhibitory compound(s) were able to
      potentiate erythromycin against the aforementioned staphylococci. The minimum
      inhibitory concentration (MIC) of erythromycin was reduced from 32 MUg/mL to 8
      MUg/mL for MRSA ATCC 43300 and MRSA SA-1 strains, and from 32-64 MUg/mL to 4
      MUg/mL for S. epidermidis 11EMB and S. hominis 13EMB strains.The genome
      sequencing and analysis of B. pumilus ICVB403 unveiled 3.666.195 nucleotides
      contained in 22 contigs with a G + C ratio of 42.0%, 3.826 coding sequences, and
      73 RNAs. In silico analysis guided identification of two putative genes coding
      for synthesis of surfactin A, a lipopeptide with 7 amino acids, and for a
      circular bacteriocin belonging to the circularin A/uberolysin family,
      respectively.

PMID- 30229514
TI  - Antimicrobial Peptides: the Achilles' Heel of Antibiotic Resistance?
AB  - Antibiotic resistance is an imminent threat to the effective treatment of
      bacterial infections, and alternative antibiotic strategies are urgently
      required. The golden epoch of antibiotics is coming to an end, and the
      development of new therapeutic agents to combat bacterial infections should be
      prioritized. This article will review the potential of antimicrobial peptides
      (AMPs) to combat the threat of antimicrobial resistance. The modern-day
      antimicrobial resistance dilemma is briefly discussed followed by a review of the
      potential of AMPs to be used alone or in combination with current antibiotics in
      order to enhance antibacterial properties of antibiotics while also potentially
      combatting resistance. This article reiterates that many AMPs exhibit direct
      microbial killing activity and also play an integral role in the innate immune
      system. These properties make AMPs attractive alternative antimicrobial agents.
      Furthermore, AMPs are promising candidates to be used as adjuvants in combination
      with current antibiotics in order to combat antibiotic resistance. Combinations
      of AMPs and antibiotics are less likely to develop resistance or transmit cross
      resistance. The further identification and therapeutic development of AMPs and
      antibiotic-AMP combinations are strongly recommended.

PMID- 30229515
TI  - Identification of a Novel Potential Probiotic Lactobacillus plantarum FB003
      Isolated from Salted-Fermented Shrimp and its Effect on Cholesterol Absorption by
      Regulation of NPC1L1 and PPARalpha.
AB  - Cholesterol-lowering activity is an important health benefit of lactic acid
      bacteria (LAB). This study aimed to screen LAB strains with cholesterol-lowering
      activities from salted fermented shrimp and evaluate probiotic characteristics
      and cholesterol-lowering potentials of these LAB isolates. Among 191 lactic acid
      strains isolated from traditional salted-fermented shrimp food, FB003 isolate
      showed the highest cholesterol-lowering activity and investigated as probiotics
      with cholesterol-lowering ability. Biochemical analysis and 16S rRNA sequencing
      revealed that this LAB isolate was Lactobacillus plantarum FB003. To screen
      probiotic trait, L. plantarum FB003 was found to be susceptible to six
      antibiotics tested and broad-spectrum antimicrobial activity. It also produced
      various enzymes such as galactosidase, glucosidase, and mannosidase. In addition,
      this strain showed autoaggregation, and coaggregation capacity for various
      pathogens. Moreover, it could adhere to Caco-2 cells and be exerted lowering
      cholesterol effects in Caco-2 cells via an upregulation of PPARalpha to inhibit
      NPC1L1 mRNA expression. Strain L. plantarum FB003 might be effective as a
      candidate probiotic with high cholesterol-lowering activity. The results of the
      present study suggest that L. plantarum FB003 have an impact on preventing high
      cholesterol level and may be used as starter culture for shrimp fermentation.

PMID- 30229516
TI  - The Relationship Among Online Sexually Explicit Material Exposure to, Desire for,
      and Participation in Rough Sex.
AB  - The broad accessibility of online sexually explicit material (SEM) exposes
      viewers to a wide scope of sexual behaviors. Social concern tends to be
      heightened over SEM that incorporates highly graphic, "rough" sex. This study
      assessed the associations among exposure to rough sex in SEM, desire for rough
      sex, and participation in rough sex while accounting for gender, sexual
      orientation, and perceived realism of SEM. Young adults (N = 327; ages 19-30;
      50.8% men) were recruited through a crowdsourcing website. They completed an
      anonymous online survey that assessed viewing frequency for a range of sexual
      behaviors in SEM, the perceived realism of SEM, desire to participate in the
      behaviors viewed, and if they had ever participated in those behaviors. Hair
      pulling, spanking, scratching, biting, bondage, fisting, and double penetration
      were used to create the variable of rough sex. Rough sex desire and participation
      were common among individuals who have been exposed to rough sex in SEM, with
      91.4% desiring to engage in 1 + behaviors at least to a small degree and 81.7%
      having engaged in 1 + behaviors. Exposure to rough sex in SEM was positively
      associated with desire for and participation in rough sex, emphasizing the need
      to ensure that individuals can distinguish between consensual rough sex and
      sexual violence. This study did not parse out causal effects or directionality,
      but did provide some insights into the interrelatedness of viewing, desiring, and
      participating in rough sex.

PMID- 30229518
TI  - Incongruence as a Variable Feature of Problematic Sexual Behaviors in an Online
      Sample of Self-Reported "Sex Addiction".

PMID- 30229517
TI  - Moral Challenges in Transgender Care: A Thematic Analysis Based on a Focused
      Ethnography.
AB  - Treatment teams providing transgender-affirming medical care are inherently faced
      with various kinds of moral and ethical dilemmas and questions, which are
      becoming even more pressing due to increasing treatment numbers and public
      attention for transgender care. Little is known about what kinds of moral and
      ethical challenges manifest in clinical practice. The aim of the present research
      was to map the moral and ethical challenges of healthcare professionals working
      in a specialized multidisciplinary transgender care center. Over a period of 7
      months, during a focused ethnographic study, data were collected through
      participant observation of multidisciplinary team meetings, observation of
      individual psychodiagnostic assessment sessions with clients, and analysis of
      transcripts and reports of a series of moral case deliberations. A thematic
      content analysis of the data identified various implicit and explicit moral and
      ethical challenges around the following six themes: (1) assessing eligibility;
      (2) content of treatment; (3) sequential order of the treatment steps; (4) role
      of the clinical guidelines; (5) differing notions regarding gender identity, and
      (6) decision-making process. Our research provides a detailed insight into the
      way healthcare professionals experience these moral and ethical challenges and
      how they are related to (local) guidelines, the multidisciplinary character of GD
      care, and its inherent implicit and explicit gender norms. Our findings suggest
      that good transgender care may profit from continuous multidisciplinary
      deliberation of and sensitivity toward the normative dimension of transgender
      care. The paper ends with recommendations for ethics support mechanisms in
      transgender care.

PMID- 30229519
TI  - Hitting the Target: Considerations for Differential Diagnosis When Treating
      Individuals for Problematic Use of Pornography.

PMID- 30229520
TI  - Understanding the Latent Structure of Hypersexuality: A Taxometric Investigation.
AB  - We examined the latent structure and taxonicity of hypersexuality in large
      university and community samples of male and female respondents. Participants
      completed the Hypersexual Behavior Inventory (HBI) and Sexual Compulsivity Scale
      (SCS), each as part of larger anonymous online surveys of sexual behavior.
      Exploratory factor analyses (EFA) were performed in part to prepare the data for
      taxometric analysis and also to identify the putative dimensions underpinning
      each measure. Three latent dimensions were identified from each of the Sexual
      Compulsivity Scale (dyscontrol, consequences, and preoccupation) and Hypersexual
      Behavior Inventory (coping, dyscontrol, and consequences). Taxometric analyses of
      the generated factors using mean above minus below a cut (MAMBAC), maximum
      covariance (MAXCOV), and latent mode factor analysis (L-Mode) broadly supported a
      dimensional latent structure for hypersexuality, particularly in female
      participants. Implications pertaining to the assessment of hypersexuality are
      discussed.

PMID- 30229521
TI  - A Life History Approach to the Female Sexual Orientation Spectrum: Evolution,
      Development, Causal Mechanisms, and Health.
AB  - Women's capacity for sexual fluidity is at least as interesting a phenomenon from
      the point of view of evolutionary biology and behavioral endocrinology as
      exclusively homosexual orientation. Evolutionary hypotheses for female
      nonheterosexuality have failed to fully account for the existence of these
      different categories of nonheterosexual women, while also overlooking broader
      data on the causal mechanisms, physiology, ontogeny, and phylogeny of female
      nonheterosexuality. We review the evolutionary-developmental origins of various
      phenotypes in the female sexual orientation spectrum using the synergistic
      approach of Tinbergen's four questions. We also present femme-specific and butch
      specific hypotheses at proximate and ultimate levels of analysis. This review
      article indicates that various nonheterosexual female phenotypes emerge from and
      contribute to hormonally mediated fast life history strategies. Life history
      theory provides a biobehavioral explanatory framework for nonheterosexual women's
      masculinized body morphology, psychological dispositions, and their elevated
      likelihood of experiencing violence, substance use, obesity, teenage pregnancy,
      and lower general health. This pattern of life outcomes can create a feedback
      loop of environmental unpredictability and harshness which destabilizes
      intrauterine hormonal conditions in mothers, leading to a greater likelihood of
      fast life history strategies, global health problems, and nonheterosexual
      preferences in female offspring. We further explore the potential of female
      nonheterosexuality to function as an alloparental buffer that enables
      masculinizing alleles to execute their characteristic fast life history
      strategies as they appear in the female and the male phenotype. Synthesizing life
      history theory with the female sexual orientation spectrum enriches existing
      scientific knowledge on the evolutionary-developmental mechanisms of human sex
      differences.

PMID- 30229522
TI  - Contributions of the Bone Microenvironment to Monoclonal Gammopathy of
      Undetermined Significance Pathogenesis.
AB  - PURPOSE OF REVIEW: MGUS (monoclonal gammopathy of undetermined significance) is a
      plasma cell disorder characterized by a moderate increase in serum monoclonal
      protein (<= 3 g/dL), an increase in bone marrow plasma cell infiltration (<= 10%)
      and the absence of any end-organ damage. Although MGUS is considered a benign
      condition, evidence for clinical consequences is increasing. In this review, we
      examine the most recent evidence regarding MGUS manifestations and risks and
      present an overview of MGUS population studies as related to bone disease. Data
      reveals important MGUS-related bone alterations that may contribute to disease
      pathogenesis. RECENT FINDINGS: MGUS patients present a rate of 1% per year risk
      of progression to the more aggressive multiple myeloma (MM) and therefore
      research has focused on the study of risk factors and the events leading to this
      progression. However, the exact health implications of MGUS itself and the
      mechanisms behind them remain unclear. It is now evident that the bone
      microenvironment plays a key role in hematologic cancers and other oncogenic
      processes leading to bone metastasis.

PMID- 30229525
TI  - A Meta-Analysis of the Effect of PCSK9-Monoclonal Antibodies on Circulating
      Lipoprotein (a) Levels.
AB  - BACKGROUND: Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein. While no
      effective therapy for Lp(a) is currently available, recently, several pooled
      analyses with small sample sizes have suggested that proprotein convertase
      subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs) could reduce
      circulating Lp(a) levels. This meta-analysis was performed to comprehensively
      investigate the efficacy of PCSK9-mAbs with respect to serum Lp(a)
      concentrations. METHODS: PubMed, MEDLINE, Embase, ClinicalTrials.gov, Cochrane
      CENTRAL, Web of Science and recent conferences up to July 2018 were searched.
      Randomized clinical trials evaluating the effect of PCSK9-mAbs and control
      treatment on plasma Lp(a) concentrations were included. Mean differences and odds
      ratios with 95% confidence intervals (CIs) were used. RESULTS: Twenty-seven
      randomized clinical trials with a total of 11,864 participants were included.
      PCSK9-mAbs showed a significant efficacy in reducing Lp(a) (- 21.9%, 95% CI -
      24.3 to - 19.5), irrespective of PCSK9-mAb types, treatment duration, participant
      characteristics, treatment methods, differences of control treatment, baseline
      Lp(a) levels, and test methods. The greatest reduction was achieved with 150 mg
      alirocumab biweekly (- 24.6%, 95% CI - 28.0 to - 21.2) and  140 mg evolocumab
      monthly (- 26.8%, 95% CI - 31.6 to - 21.9). Meta-regression analyses found that
      the more intense low-density lipoprotein cholesterol levels declined during PCSK9
      mAb treatment, the greater the reduction in Lp(a) levels. Safety was in
      accordance with previous reports. CONCLUSIONS: The results of this analysis
      suggested that PCSK9-mAbs could significantly reduce circulating Lp(a) levels.
      Long-term studies may be needed to confirm the effect of PCSK9-mAbs on Lp(a) in
      the future.

PMID- 30229524
TI  - Barriers to compliance with emergency department discharge instructions: lessons
      learned from patients' perspectives.
AB  - The objective of this study is to understand patients' perspectives about system
      based barriers that may influence decision-making regarding following discharge
      instructions. In this qualitative study, subjects were interviewed by phone 1-4
      weeks following being discharged to home from the emergency department (ED). We
      used a semi-structured interview guide to ask a series of open-ended questions
      about subjects' recent ED visit and subsequent course, including discharge
      instructions, whether or not they complied with those instructions, and reasoning
      behind their decisions to follow-up or not. All interviews were recorded and
      transcribed to identify themes among the transcripts, which were analyzed to
      identify barriers to compliance. While the majority of those interviewed
      expressed no specific concerns or challenges, four system-based themes did emerge
      regarding patient attitudes toward and experiences with discharge instructions.
      They were: (1) failure to ensure clarity about diagnosis at the time of discharge
      from the ED, (2) failure to identify patients' feelings of hopelessness regarding
      the utility of follow-up, (3) difficulty in scheduling follow-up appointments,
      and (4) the importance of a clear discharge process. This study finds several
      system-based barriers might influence compliance. The four identified themes
      suggest a recurring cycle of visiting the ED, being discharged to primary care or
      specialists, and ultimately returning to the ED. We propose that systems-based
      interventions may help to break this cycle.

PMID- 30229526
TI  - Annual Congress of the European Association of Nuclear Medicine October 13 - 17,
      2018 Dusseldorf, Germany.

PMID- 30229523
TI  - Cognitive challenges while at work and work output in breast cancer survivors
      employed in a rapidly evolving economy.
AB  - OBJECTIVE: To determine whether work output was related to cognitive limitations
      while at work in occupationally active breast cancer survivors (BCS) employed in
      a rapidly developing economy. METHODS: Measures of demographics, job type, job
      stress, general distress (anxiety, depression), fatigue, work-related cognitive
      limitations, and work output were obtained using self-report measures in a cross
      sectional study in both BCS and controls (n = 267/group). RESULTS: Groups had
      similar educational backgrounds, job types, and levels of job stress. The BCS
      group was a median of 3.2 years post-primary treatment, slightly older, more
      likely to be divorced, have children, and was more likely working part-time. The
      BCS group reported higher levels of fatigue, general distress, and lower levels
      of work output (p < .05). A multivariate regression adjusting for group
      differences indicated that cognitive symptoms at work were related to lower
      levels of quantity, quality, and timeliness of completed work in the BCS group
      (adj. R2 = .57, unstandardized coefficient = 1.062, 95% CI = .436 to 1.689).
      CONCLUSION: When reported in the context of work, cognitive limitations were
      associated with lower levels of reported work output exclusively in the BCS
      group. IMPLICATIONS FOR CANCER SURVIVORS: This study provides further evidence
      that cognitive limitations reported in the context of work in a developing
      country is similar to that of BCS working in more developed economies and is
      specific to BCS and not healthy workers with similar job types and job stress.
      Solutions to this problem may be applicable across countries.

PMID- 30229527
TI  - A prospective study of the feasibility of FDG-PET/CT imaging to quantify
      radiation-induced lung inflammation in locally advanced non-small cell lung
      cancer patients receiving proton or photon radiotherapy.
AB  - PURPOSE: This prospective study assessed the feasibility of 18F-2-fluoro-2-deoxy
      D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) to
      quantify radiation-induced lung inflammation in patients with locally advanced
      non-small cell lung cancer (NSCLC) who received radiotherapy (RT), and compared
      the differences in inflammation in the ipsilateral and contralateral lungs
      following proton and photon RT. METHODS: Thirty-nine consecutive patients with
      NSCLC underwent FDG-PET/CT imaging before and after RT on a prospective study. A
      novel quantitative approach utilized regions of interest placed around the
      anatomical boundaries of the lung parenchyma and provided lung mean standardized
      uptake value (SUVmean), global lung glycolysis (GLG), global lung parenchymal
      glycolysis (GLPG) and total lung volume (LV). To quantify primary tumor metabolic
      response to RT, an adaptive contrast-oriented thresholding algorithm was applied
      to measure metabolically active tumor volume (MTV), tumor uncorrected SUVmean,
      tumor partial volume corrected SUVmean (tumor-PVC-SUVmean), and total lesion
      glycolysis (TLG). Parameters of FDG-PET/CT scans before and after RT were
      compared using two-tailed paired t-tests. RESULTS: All tumor parameters after
      either proton or photon RT decreased significantly (p < 0.001). Among the 21
      patients treated exclusively with proton RT, no significant increase in PVC
      SUVmean or PVC-GLPG was observed in ipsilateral lungs after the PVC parameters of
      primary tumor were subtracted (p = 0.114 and p = 0.453, respectively). Also,
      there were no significant increases in SUVmean or GLG of contralateral lungs of
      patients who received proton RT (p = 0.841, p = 0.241, respectively). In
      contrast, among the nine patients who received photon RT, there was a
      statistically significant increase in PVC-GLPG of ipsilateral lung (p < 0.001)
      and in GLG of contralateral (p = 0.036) lung. In the subset of nine patients who
      received a combined proton and photon RT, there was a statistically significant
      increase in PVC-GLPG of ipsilateral lung (p < 0.001). CONCLUSION: Our data
      suggest less induction of inflammatory response in both the ipsilateral and
      contralateral lungs of patients treated with proton compared to photon or
      combined proton-photon RT.

PMID- 30229530
TI  - Outliers and Influential Observations in Exponential Random Graph Models.
AB  - We discuss measuring and detecting influential observations and outliers in the
      context of exponential family random graph (ERG) models for social networks. We
      focus on the level of the nodes of the network and consider those nodes whose
      removal would result in changes to the model as extreme or "central" with respect
      to the structural features that "matter". We construe removal in terms of two
      case-deletion strategies: the tie-variables of an actor are assumed to be
      unobserved, or the node is removed resulting in the induced subgraph. We define
      the difference in inferred model resulting from case deletion from the
      perspective of information theory and difference in estimates, in both the
      natural and mean-value parameterisation, representing varying degrees of
      approximation. We arrive at several measures of influence and propose the use of
      two that do not require refitting of the model and lend themselves to routine
      application in the ERGM fitting procedure. MCMC p values are obtained for testing
      how extreme each node is with respect to the network structure. The influence
      measures are applied to two well-known data sets to illustrate the information
      they provide. From a network perspective, the proposed statistics offer an
      indication of which actors are most distinctive in the network structure, in
      terms of not abiding by the structural norms present across other actors.

PMID- 30229528
TI  - Improved specificity with 68Ga PSMA PET/CT to detect clinically significant
      lesions "invisible" on multiparametric MRI of the prostate: a single institution
      comparative analysis with radical prostatectomy histology.
AB  - PURPOSE: Positron emission tomography (PET) for prostate-specific membrane
      antigen (PSMA) represents a promising method for prostate cancer diagnosis and
      staging. Comparisons of PSMA-based tumour characterisation to multiparametric MRI
      (mpMRI) are limited, hence this study sought to compare the diagnostic accuracy
      of 68Ga-PSMA PET/CT to mpMRI against radical prostatectomy (RP) whole gland
      histopathology. METHODS: A retrospective cohort study of consecutive patients who
      underwent pre-operative mpMRI and 68Ga-PSMA PET/CT followed by a RP was
      performed. Standard clinical parameters were collected. "Per patient" and "per
      lesion" analyses for image-based detection according to RP histopathology were
      described using sensitivity, specificity and other measures of diagnostic
      accuracy. RESULTS: Fifty-eight patients (median age 65.5 years, median PSA 7.35
      ng/mL) underwent RP, resulting in a high-risk cohort (>=pT3 69%). Sensitivities
      for identification of index lesion, bilateral and multifocal disease were 90%,
      21%, 19% for mpMRI and 93%, 42%, 34% for 68Ga-PSMA PET/CT. Histology analyses
      revealed 88 cancer foci of Gleason grades 3 + 3 (4%), 3 + 4 (64%), 4 + 3 (19%), 4
      + 4 (3%) and >= 4 + 5 (10%), of which 68Ga-PSMA PET/CT correctly detected more
      foci (78%, AUC 0.817) than mpMRI (69%, AUC 0.729). CONCLUSIONS: 68Ga-PSMA PET/CT
      may better reflect RP histopathology compared to mpMRI when considering
      multifocal and bilateral disease. These findings may influence surgical planning,
      targeted biopsy and focal therapy strategies and require further research.

PMID- 30229531
TI  - Contribution to the Species of Oxyligyrus Arrow (Coleoptera, Melolonthidae) of
      the Peruanus Species Group with the Description of Two New Species.
AB  - Two new species of the genus Oxyligyrus Arrow, 1908 from the peruanus species
      group are described from Brazil and compared with other species of the genus
      Oxyligyrus limeirai sp. nov., from Maranhao state and Oxyligyrus vazdemelloi sp.
      nov. from Mato Grosso state. A key to the peruanus complex and a distribution map
      of their known brazilian localities is also provided. New state records from
      Brazil are also presented for Oxyligyrus zoilus (Olivier 1789) the most
      widespread species of the genus and for O. acutus Endrodi, 1966.

PMID- 30229529
TI  - Examining the readiness of best evidence in medical education guides for
      integration into educational practice: A meta-synthesis.
AB  - BACKGROUND: To support evidence-informed education, health professions education
      (HPE) stakeholders encourage the creation and use of knowledge syntheses or
      reviews. However, it is unclear if these knowledge syntheses are ready for
      translation into educational practice. Without understanding the readiness,
      defined by three criteria-quality, accessibility and relevance-we risk
      translating weak evidence into practice and/or providing information that is not
      useful to educators. METHODS: A librarian searched Web of Science for knowledge
      syntheses, specifically Best Evidence in Medical Education (BEME) Guides. This
      meta-synthesis focuses on BEME Guides because of their explicit goal to inform
      educational practice and policy. Two authors extracted data from all Guides,
      guided by the 25-item STructured apprOach to the Reporting In healthcare
      education of Evidence Synthesis (STORIES). RESULTS: Forty-two Guides published in
      Medical Teacher between 1999 and 2017 were analyzed. No Guide met all STORIES
      criteria, but all included structured summaries and most described their
      literature search (n = 39) and study inclusion/exclusion (n = 40) procedures.
      Eleven Guides reported the presence of theory and/or educational principles, and
      eight consulted with external subject matter experts. Accessibility to each
      Guide's full-text and supplemental materials was variable. DISCUSSION: For a
      subset of HPE knowledge syntheses, BEME Guides, this meta-synthesis identifies
      factors that support readiness and indicates potential areas of improvement, such
      as consistent access to Guides and inclusion of external subject matter experts
      on the review team. This analysis is useful for understanding the current
      readiness of HPE knowledge syntheses and informing future reviews to evolve so
      they can catalyze translation of evidence into educational practice.

PMID- 30229532
TI  - Development and content validity of a hemodialysis symptom patient-reported
      outcome measure.
AB  - PURPOSE: To describe the process and preliminary qualitative development of a new
      symptom-based patient-reported outcome measure (PROM) intended to assess
      hemodialysis treatment-related physical symptoms. METHODS: Experienced
      interviewers conducted concept elicitation and cognitive debriefing interviews
      with individuals receiving in-center hemodialysis in the United States. Concept
      elicitation interviews involved eliciting spontaneous reports of symptom
      experiences and probing to further explore and confirm concepts. We used patient
      reported concepts to generate a preliminary symptom PROM. We conducted 3 rounds
      of cognitive debriefing interviews to evaluate symptom relevance, item
      interpretability, and draft item structure. We iteratively refined the measure
      based on cognitive interview findings. RESULTS: Forty-two adults receiving in
      center hemodialysis participated in the concept elicitation interviews. A total
      of 12 symptoms were reported by > 10% of interviewees. We developed a 13-item
      initial draft instrument for testing in 3 rounds of cognitive interviews with an
      additional 52 hemodialysis patients. Participant responses and feedback during
      cognitive interviews led to changes in symptom descriptions, division of the
      single item "nausea/vomiting" into 2 distinct items, removal of daily activity
      interference items, addition of instructions, and clarification about the recall
      period, among other changes. CONCLUSIONS: Symptom Monitoring on Renal Replacement
      Therapy-Hemodialysis (SMaRRT-HDTM) is a 14-item PROM intended for use in
      hemodialysis patents. SMaRRT-HDTM uses a single treatment recall period and a 5
      point Likert scale to assess symptom severity. Qualitative interview data provide
      evidence of its content validity. SMaRRT-HDTM is undergoing additional testing to
      assess measurement properties and inform measure scoring.

PMID- 30229533
TI  - Problems persist in reporting of methods and results for the WOMAC measure in hip
      and knee osteoarthritis trials.
AB  - PURPOSE: The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is
      a commonly used outcome measure for osteoarthritis. There are different versions
      of the WOMAC (Likert, visual analogue or numeric scales). A previous review of
      trials published before 2010 found poor reporting and inconsistency in how the
      WOMAC was used. This review explores whether these problems persist. METHODS:
      This systematic review included randomised trials of hip and/or knee
      osteoarthritis published in 2016 that used the WOMAC. Data were extracted on the
      version used, score range, analysis and results of the WOMAC, and whether these
      details were clearly reported. RESULTS: This review included 62 trials and 41
      reported the WOMAC total score. The version used and item range for the WOMAC
      total score were unclear in 44% (n = 18/41) and 24% (n = 10/41) of trials,
      respectively. The smallest total score range was 0-10 (calculated by averaging 24
      items scored 0-10); the largest was 0-2400 (calculated by summing 24 items scored
      0-100). All trials reported the statistical analysis methods but only 29%
      reported the between-group mean difference and 95% confidence interval.
      CONCLUSION: Details on the use and scoring of the WOMAC were often not reported.
      We recommend that trials report the version of the WOMAC and the score range
      used. The between-group treatment effect and corresponding confidence interval
      should be reported. If all the items of the WOMAC are collected, the total score
      and individual subscale scores should be presented. Better reporting would
      facilitate the interpretation, comparison and synthesis of the WOMAC score in
      trials.

PMID- 30229534
TI  - Intensive Parenting: Fertility and Breastfeeding Duration in the United States.
AB  - Using 30 years of longitudinal data from a nationally representative cohort of
      women, we study the association between breastfeeding duration and completed
      fertility, fertility expectations, and birth spacing. We find that women who
      breastfeed their first child for five months or longer are a distinct group. They
      have more children overall and higher odds of having three or more children
      rather than two, compared with women who breastfeed for shorter durations or not
      at all. Expected fertility is associated with initiating breastfeeding but not
      with how long mothers breastfeed. Thus, women who breastfeed longer do not differ
      significantly from other breastfeeding women in their early fertility
      expectations. Rather, across the life course, these women achieve and even exceed
      their earlier fertility expectations. Women who breastfeed for shorter durations
      (1-21 weeks) are more likely to fall short of their expected fertility than to
      achieve or exceed their expectations, and they are significantly less likely than
      women who breastfeed for longer durations (>=22 weeks) to exceed their expected
      fertility. In contrast, women who breastfeed longer are as likely to exceed as to
      achieve their earlier expectations, and the difference between their probability
      of falling short versus exceeding their fertility expectations is relatively
      small and at the boundary of statistical significance (p = .096). These
      differences in fertility are not explained by differences in personal and family
      resources, including family income or labor market attachment. Our findings
      suggest that breastfeeding duration may serve as a proxy for identifying a
      distinct approach to parenting. Women who breastfeed longer have reproductive
      patterns quite different than their socioeconomic position would predict. They
      both have more children and invest more time in those children.

PMID- 30229535
TI  - Intraosseous schwannoma of the mobile spine: a report of twenty cases.
AB  - PURPOSE: To clarify the clinical features, surgical strategies, and outcomes of
      intraosseous schwannoma (IOS) of the mobile spine. METHODS: We retrospectively
      reviewed patients with primary benign spinal schwannoma who underwent surgery in
      our orthopedic department. RESULTS: A total of 101 patients with primary benign
      schwannoma located in the mobile spine underwent surgery in our orthopedic
      department from 2005 to 2015. Twenty-five patients presented with aggressive
      features. Twenty patients were regularly followed up, twelve with lesions in the
      cervical spine, six with lesions in the thoracic region, and two with lesions in
      the lumbar spine. Preoperative CT-guided biopsy was performed in fourteen cases;
      the accuracy of diagnosis was 100%, and IOS is not histologically different from
      conventional schwannoma. The computed tomography (CT) scan revealed expansile and
      osteolytic bone destruction in all these cases, with six patients having
      pathological fracture. On T2-weighted magnetic resonance imaging, the lobulated
      schwannomas showed heterogeneous signal intensity and significant heterogeneous
      enhancement on post-contrast images. Gross total resection was performed in
      seventeen patients and subtotal resection in three. Tumor-involved nerve roots
      resection were documented to decrease local recurrence in fourteen cases. The
      visual analog scale score decreased from 5.66 +/- 1.79 preoperatively to 1.16 +/-
      1.77 at the final follow-up. No local recurrence was noticed at the final follow
      up. CONCLUSION: CT-guided biopsy is effective for the preoperative diagnosis of
      spinal IOS. Total resection is the optimal treatment for IOS, whereas subtotal
      resection could be an alternative choice for high-risk cases. These slides can be
      retrieved under electronic supplementary material.

PMID- 30229536
TI  - Value of sharing and networking among birth defects surveillance programs: an
      ICBDSR perspective.
AB  - Birth defects (BD), also known as congenital anomalies, are structural or
      functional abnormalities present at birth as a result of abnormal prenatal
      development. Their cause can be broadly categorized as genetic, environmental, or
      a combination of both. It is estimated that approximately 3-6% of newborn infants
      worldwide are affected by BD, many of which are associated with serious
      morbidity, mortality, and lifelong disabilities. The International Clearinghouse
      for Birth Defects Surveillance and Research (ICBDSR), founded in 1974, promotes
      worldwide birth defect surveillance, research, and prevention through the ongoing
      sharing of data, expertise, and training. In this review, we show value and
      contribution of BD surveillance systems in pursuing these aims. In the time of
      personalized medicine for many rare and common diseases, there are still massive
      gaps in our understanding of the causes and mechanisms of many birth defects,
      especially structural congenital anomalies. The main aim of the Sustainable
      Development Goals (SDGs), adopted by the United Nations in 2015, is to ensure
      healthy lives and promote well-being for all children. One specific goal is to
      end preventable deaths of newborns and children less than 5 years of age by 2030.
      The SDGs also underscore the need to consider BD as a priority in the global
      child health agenda. It can be said that counting BD helps BD to count. By
      sharing data and expertise and joining in surveillance and research, BD
      surveillance programs can play a major role in increasing our understanding of
      the causes of BD, and promoting prevention.

PMID- 30229537
TI  - Direct-to-consumer carrier screening for cystic fibrosis via a hospital website:
      a 6-year evaluation.
AB  - A Dutch university hospital started offering cystic fibrosis (CF) carrier
      screening directly to consumers (DTC) through their website in 2010. A 6-year
      process evaluation was conducted to evaluate the offer. Screening was implemented
      as intended. However, uptake was lower than expected. Forty-four tests have been
      requested, partly by couples with a positive family history for CF, which was not
      the intended target group. Users were generally positive about the screening
      offer, citing accessibility, ease of testing, anonymity, and perceived
      shortcomings of regular healthcare as reasons for requesting screening. DTC CF
      carrier screening via a university hospital website is feasible, but is seldom
      used. Considering technological advances, continuation of this specific offer is
      questionable.

PMID- 30229538
TI  - Congenital disorders: epidemiological methods for answering calls for action.

PMID- 30229539
TI  - Insulin Receptor Substrate Suppression by the Tyrphostin NT157 Inhibits Responses
      to Insulin-Like Growth Factor-I and Insulin in Breast Cancer Cells.
AB  - Insulin and insulin-like growth factor (IGF) signaling systems regulate breast
      cancer growth, progression, and metastasis. The insulin receptor substrates 1 and
      2 (IRS1/2) transduce signaling from the type I IGF receptor (IGF-IR) and insulin
      receptor (InR) to mediate the biological effects of receptor activation. In
      breast cancer, IRS-1 plays a critical role in cancer cell proliferation while IRS
      2 is associated with motility and metastasis. NT157, a small-molecule tyrphostin,
      downregulates IRS proteins in several model systems. In breast cancer cells,
      NT157 treatment suppressed IRS protein expression in a dose-dependent manner.
      Exposure to NT157 inhibited the activation of downstream signaling mediated by
      the IRS proteins. NT157 induced a MAPK-dependent serine phosphorylation of IRS
      proteins which resulted in disassociation between IRS proteins and their
      receptors resulting in IRS degradation. In estrogen receptor-alpha-positive
      (ERalpha+) breast cancer cells (MCF-7 and T47D), NT157 also resulted in
      cytoplasmic ERalpha downregulation likely because of disruption of an IRS-1-IGF
      IR/InR/ERalpha complex. NT157 decreased S phase fraction, monolayer, and
      anchorage-independent growth after IGF/insulin treatment in ERalpha+ breast
      cancer cells. NT157 downregulation of IRS protein expression also sensitized
      ERalpha+ breast cancer cells to rapamycin. Moreover, NT157 inhibited the growth
      of tamoxifen-resistant ERalpha+ breast cancer cells. Given that both IGF-IR and
      InR play a role in cancer biology, targeting of IRS adaptor proteins may be a
      more effective strategy to inhibit the function of these receptors.

PMID- 30229540
TI  - Contribution of capsaicin-sensitive innervation to the continuous eruption of the
      rat mandibular incisors.
AB  - A major component of tooth innervation is made of capsaicin-sensitive primary
      afferents (CSPA). These fibers play a key role in tooth pain and inflammation;
      little is known, however, about the role of CSPA in tooth eruption. The aim of
      this study was to examine the role of the capsaicin-sensitive afferents in the
      process of eruption of intact rat incisors. CSPA fibers in several rat groups,
      were subjected to one of the following experimental procedures: systemic chemical
      ablation, systemic ablation followed by chemical sympathectomy and localized
      activation. The observed effects on incisor eruption were compared to those made
      on controls. The total amount of eruption in control/naive rats, measured over a
      total period of 144 h, was 3.18 +/- 0.07 mm and decreased to 2.43 +/- 0.08 mm (n
      = 7; p < 0.001) following systemic ablation of CSPA. Further decrease to 2.24 +/-
      0.08 mm (n = 7; p < 0.001) was noticed when chemical sympathectomy was added to
      CSPA ablation. The average rate of eruption was 1.7 +/- 0.25 mm following CSPA
      activation, compared to an average of 0.8 +/- 0.07 mm for controls (n = 7; p <
      0.001). Capsaicin sensitive fibers play an important role in tooth homeostasis,
      and intact neural supply is required for tooth growth under normal conditions.

PMID- 30229542
TI  - Handgrip dynamometry for continuous assessment of volitional control during
      induction of anesthesia: a prospective observational study.
AB  - PURPOSE: Response to commands is the gold standard to assess the level of
      consciousness during anesthesia induction but it only provides an intermittent,
      binary measure with low temporal resolution. To overcome these limitations, we
      combined the object hold method with handgrip dynamometry to continuously record
      the force applied to hold a dynamometer as a surrogate measure of the level of
      consciousness during induction of anesthesia. METHODS: Fourteen patients
      scheduled for elective lumbar surgery and 14 age-matched non-anesthetized
      controls were enrolled. The subjects held the dynamometer with their dominant
      hand for as long as possible (patients) or until told to stop (controls). After a
      one-minute baseline, propofol was infused (1.0 mg.kg-1.min-1) to the patient
      group until the subject dropped the dynamometer, which defined the object hold
      time. Three additional patients were also asked intermittently to squeeze the
      dynamometer during the propofol infusion to determine any retained ability to
      exert a strong grip despite any grip changes during induction. RESULTS: The mean
      (standard deviation) object hold time was 115 (22) seconds after the start of the
      propofol infusion. There was a progressive significant linear decrease (R2 =
      0.98; P < 0.001) in dynamometry-determined handgrip force starting approximately
      74 seconds before object drop. Age was inversely related to the object hold time
      (R2 = 0.47, P < 0.01). The three additional propofol induction patients had
      strong intermittent grip strength despite progressive decreases in the hold
      force. Of the 17 patients who completed the object hold task (14 with the
      standard protocol and three with intermittent squeeze requests), 16 (94%; 95%
      confidence interval, 76 to 99%) did not respond to verbal commands after dropping
      the dynamometer. CONCLUSION: Handgrip dynamometry can be used to continuously
      track volitional control during induction of anesthesia while also reliably
      showing a gradual loss of consciousness. This method could be useful for studies
      investigating mechanisms of anesthesia.

PMID- 30229543
TI  - Pilot Study of a Single Session Heart Rate Variability Biofeedback Intervention
      on Veterans' Posttraumatic Stress Symptoms.
AB  - Veterans with posttraumatic stress symptoms exhibit reduced heart rate
      variability characteristic of autonomic nervous system dysregulation. Studies
      show heart rate variability biofeedback (HRVB) is effective in reducing
      posttraumatic stress symptoms by improving autonomic functioning. Participants in
      this pilot study were veterans of different war eras with military-related
      posttraumatic stress symptoms. The study aims were to examine the impact of a
      single session HRVB intervention on posttraumatic stress symptoms and heart rate
      variability, test persistence of effects, and determine if veterans would find
      the intervention acceptable. One group (n = 6) received training in diaphragmatic
      breathing and heart rate variability biofeedback, augmented by twice-daily
      practice using a smart phone and breath pacing app. A second group (n = 6)
      received only a single session of diaphragmatic breathing training. After 4
      weeks, participants in the second group (n = 5) received the full intervention.
      HRVB significantly reduced global posttraumatic stress symptoms, whereas
      diaphragmatic breathing alone did not. Further, veterans found the approach
      acceptable, as demonstrated by a high degree of adherence with prescribed
      practice, low study attrition, and continued use over time. Results of this pilot
      study warrant further refinement of a protocol utilizing mHealth to treat
      posttraumatic stress symptoms in military populations.

PMID- 30229541
TI  - Pediatric Multiple Sclerosis: an Update.
AB  - PURPOSE OF REVIEW: Diagnostic criteria for pediatric-onset multiple sclerosis
      (POMS) and related demyelinating disorders have been updated, neuroimaging
      studies have revealed new insights, biological assays identify patients with
      specific antibodies that influence both diagnosis and treatment, clinical trials
      are informing on treatment efficacy and safety, and longitudinal studies of
      neurological, cognitive and quality of life outcomes are informing on the impact
      of these diseases. We provide updates to assist providers caring for these
      children. RECENT FINDINGS: The recent 2017 McDonald Criteria for MS provide a
      simplified means to confirm diagnosis at onset and over time, and have been shown
      to be equally applicable for POMS. MRI analyses demonstrate that brain volume is
      reduced at onset, and that both volumetric and tissue integrity measures decline
      over time, indicating that POMS shares the degenerative aspects that also
      characterize adult-onset disease. The presence of myelin oligodendrocyte
      glycoprotein (MOG) antibodies at onset is detected in more than 50% of children
      with acute disseminated encephalomyelitis. When persistent over time, they are
      associated with relapsing disease. The first randomized clinical trials of
      disease supports superiority of fingolimod over subcutaneous interferon beta 1a,
      and demonstrated a favorable safety profile. Finally, while Expanded Disability
      Status Scale (EDSS) scores remain low in the first 10 years post-onset, POMS is
      associated with high rates of patient-reported fatigue and reduced engagement in
      exercise and carries a risk for cognitive impairment. The past 15 years have
      borne witness to a marked expansion in recognition and research in POMS. There
      are now more specific diagnostic criteria, antibodies to CNS proteins appear to
      define diagnostically distinct disorders, clinical trials have successfully
      launched and one has completed, and we are gaining increasing appreciation of the
      impact of MS and related disorders on the lived experience of children and
      adolescents.

PMID- 30229544
TI  - Effective inhibition of different Japanese encephalitis virus genotypes by RNA
      interference targeting two conserved viral gene sequences in vitro and in vivo.
AB  - Japanese encephalitis is a zoonotic, mosquito-borne, infectious disease caused by
      Japanese encephalitis virus (JEV), which is prevalent in China. At present, there
      are no specific drugs or therapies for JEV infection, which can only be treated
      symptomatically. Lentivirus-mediated RNA interference (RNAi) is a highly
      efficient method to silence target genes. In this study, two lentiviral shRNA, LV
      C and LV-NS5, targeting the conserved viral gene sequences were used to inhibit
      different JEV genotypes strains in BHK21 cells and mice. The results showed that
      LV-C significantly inhibited JEV genotype I and genotype III strains in cells and
      mice. Quantitative RT-PCR analysis showed that JEV mRNA were reduced by 83.2
      90.9% in cells by LV-C and that flow cytometry analysis confirmed the inhibitory
      activity of LV-C. The viral titers were reduced by about 1000-fold in cells and
      the brains of suckling mice by LV-C, and the pretreatment of LV-C protected 60
      80% of mice against JEV-induced lethality. The inhibitory activities of LV-NS5 in
      cells and mice were weaker than those of LV-C. These results indicate that RNAi
      targeting of the two conserved viral gene sequences had significantly suppressed
      the replication of different JEV genotypes strains in vitro and in vivo,
      highlighting the feasibility of RNAi targeting of conserved viral gene sequences
      for controlling JEV infection.

PMID- 30229545
TI  - The Mode of Action of an Anti-Oligomeric Amyloid beta-Protein Antibody Affects
      its Protective Efficacy.
AB  - The process of developing antibody drugs for Alzheimer's disease therapy has been
      both long and difficult; however, recent advances suggest that antibodies against
      neurotoxic Alphabeta42 can suppress the progression of AD, especially on its
      early stage. Here, we obtained and characterized a novel anti-oligomeric Abeta42
      aggregate scFv antibody, HT7, which could induce the significant disaggregation
      of Abeta42 aggregates through the release of stable and non-cytotoxic hexameric
      complexes that were composed of three scFv HT7s and one Abeta42 trimer, the
      latter being found to serve as the assembled subunit within larger Abeta42
      aggregates in addition to existing freely between the cells. The docking model of
      the scFv HT7-Abeta42 complex revealed that only the N-terminal peptide of the
      Abeta42 molecule was bound into the groove between the VH and VL domains of scFv
      HT7. Thus, it was suggested that the hydrophobic interaction between the C
      terminal peptides of Abeta42 molecules maintained the stability of the Abeta42
      trimers or the Abeta42 trimer subunits. The saturation of Abeta42 trimer subunits
      by scFv HT7 and the subsequent dissociation of the scFv HT7-saturated Abeta42
      trimer subunits from larger Abeta42 aggregates constituted the primary mechanisms
      underlying the high efficacy of scFv HT7. Our findings revealed that it was not
      sufficient for an anti-oligomeric Abeta42 antibody to exhibit high specificity
      and high affinity to the oligomeric Abeta42 aggregates in order to promote
      Abeta42 aggregate clearance and neutralize their cytotoxic effects. Here, for the
      first time, we proposed a "post-saturation dissociation" mechanism of Abeta42
      oligomeric subunits for effective anti-Abeta42 antibodies.

PMID- 30229546
TI  - Brief Overview of Prostate Cancer Statistics, Grading, Diagnosis and Treatment
      Strategies.
AB  - This chapter provides a brief overview of prostate cancer statistics, grading,
      diagnosis and treatment strategies that are discussed in more detail in the
      subsequent chapters of this book and the companion book titled "Clinical
      Molecular and Diagnostic Imaging of Prostate Cancer and Treatment Strategies". It
      also points to websites that provide additional useful information for patients
      affected by prostate cancer and for students and teachers to obtain practical and
      updated information on research, new diagnostic modalities and new therapies
      including new updated clinical trials. Three sections are focused on overview of
      prostate cancer statistics; overview of detection, diagnosis, stages and grading
      of prostate cancer; and treatment possibilities and options.

PMID- 30229547
TI  - Novel Biomarkers for Prostate Cancer Detection and Prognosis.
AB  - Prostate cancer (PCa) remains as one of the most controversial issues in health
      care because of the dilemmas related to screening using Prostate Specific Antigen
      (PSA). A high number of false positive biopsies and an elevated rate of
      overdiagnosis are the main problems associated with PSA. New PCa biomarkers have
      been recently proposed to increase the predictive value of PSA. The published
      results showed that PCA3 score, Prostate Health Index and 4Kscore can reduce the
      number of unnecessary biopsies, outperforming better than PSA and the percentage
      of free PSA. Furthermore, 4Kscore provides with high accuracy an individual risk
      for high-grade PCa. High values of PHI are also associated with tumor
      aggressiveness. In contrast, the relationship of PCA3 score with aggressiveness
      remains controversial, with studies showing opposite conclusions. Finally, the
      development of molecular biology has opened the study of genes, among them
      TMPRSS2:ERG fusion gene and miRNAs, in PCa detection and prognosis.

PMID- 30229548
TI  - Inflammation and Prostate Cancer.
AB  - Chronic inflammation resulting from infections, altered metabolism, inflammatory
      diseases or other environmental factors can be a major contributor to the
      development of several types of cancer. In fact around 20% of all cancers are
      linked to some form of inflammation. Evidence gathered from genetic,
      epidemiological and molecular pathological studies suggest that inflammation
      plays a crucial role at various stages of prostatic carcinogenesis and tumor
      progression. These include initiation, promotion, malignant conversion, invasion,
      and metastasis. Detailed basic and clinical research in these areas, focused
      towards understanding the etiology of prostatic inflammation, as well as the
      exact roles that various signaling pathways play in promoting tumor growth, is
      critical for understanding this complex process. The information gained would be
      useful in developing novel therapeutic strategies such as molecular targeting of
      inflammatory mediators and immunotherapy-based approaches.

PMID- 30229549
TI  - The Impact of Centrosome Pathologies on Prostate Cancer Development and
      Progression.
AB  - The significant role of centrosomes in cancer cell proliferation has been well
      recognized (reviewed in Schatten H, Histochem Cell Biol 129:667-86 (2008);
      Schatten H, Sun Q-Y, Microsc Microanal 17(4):506-512 (2011); Schatten H, Sun Q-Y,
      Reprod Fertil Dev. https://doi.org/10.1071/RD14493 (2015a); Schatten H, Sun Q-Y,
      Centrosome-microtubule interactions in health, disease, and disorders. In:
      Schatten H (ed) The cytoskeleton in health and disease. Springer Science+Business
      Media, New York (2015b)) and new research has generated new interest and new
      insights into centrosomes as potential targets for cancer-specific therapies. The
      centrosome is a key organelle serving multiple functions through its primary
      functions as microtubule organizing center (MTOC) that is also an important
      communication center for processes involved in cellular regulation; transport to
      and away from centrosome-organized microtubules along microtubules is essential
      for cellular activities including signal transduction and metabolic activities.
      New research on cancer cell centrosomes has generated new insights into
      centrosome dysfunctions in cancer cells in which centrosome phosphorylation,
      balance of centrosomal proteins, centrosome regulation and duplication are
      impaired. Among the hallmarks of cancer cells are multipolar spindles or abnormal
      bipolar spindles that are formed as a result of centrosome protein expression
      imbalances, abnormalities in centrosome structure and abnormalities in clustering
      of centrosomal components that are critical for bipolar mitotic apparatus
      formation. Centrosome abnormalities in cancer cells can be the result of multiple
      factors including environmental influences and toxicants that can affect
      centrosome functions by inducing centrosome pathologies leading to abnormal
      cancer cell proliferation. These topics are addressed in this review with focus
      on prostate-specific therapy strategies to target centrosome abnormalities. We
      will also address loss of cell polarity in cancer cells in which centrosome
      dysfunctions play a role as well as the loss of primary cilia in prostate cancer
      development and progression.

PMID- 30229550
TI  - MicroRNAs as Regulators of Prostate Cancer Metastasis.
AB  - Prostate cancer causes significant morbidity in men and metastatic disease is a
      major cause of cancer related deaths. Prostate metastasis is controlled by
      various cellular intrinsic and extrinsic factors, which are often under the
      regulatory control of various metastasis-associated genes. Given the dynamic
      nature of metastatic cancer cells, the various factors controlling this process
      are themselves regulated by microRNAs which are small non-coding RNAs.
      Significant research work has shown differential microRNA expression in primary
      and metastatic prostate cancer suggesting their importance in prostate
      pathogenesis. We will review the roles of different microRNAs in controlling the
      various steps in prostate metastasis.

PMID- 30229551
TI  - Epithelial-Mesenchymal Transition (EMT) and Prostate Cancer.
AB  - Typically the normal epithelial cells are a single layer, held tightly by
      adherent proteins that prevent the mobilization of the cells from the monolayer
      sheet. During prostate cancer progression, the epithelial cells can undergo
      epithelial-mesenchymal transition or EMT, characterized by morphological changes
      in their phenotype from cuboidal to spindle-shaped. This is associated with
      biochemical changes in which epithelial cell markers such as E-cadherin and
      occludins are down-regulated, which leads to loss of cell-cell adhesion, while
      mesenchymal markers such as vimentin and N-cadherin are up-regulated, thereby
      allowing the cells to migrate or metastasize to different organs. The EMT
      transition can be regulated directly and indirectly by multiple molecular
      mechanisms including growth factors and cytokines such as transforming growth
      factor-beta (TGF-beta), epidermal growth factor (EGF) and insulin-like growth
      factor (IGF), and signaling pathways such as mitogen-activated protein kinase
      (MAPK) and Phosphatidylinositol 3-Kinase (PI3K). This signaling subsequently
      induces expression of various transcription factors like Snail, Twist, Zeb1/2,
      that are also known as master regulators of EMT. Various markers associated with
      EMT have been reported in prostate cancer patient tissue as well as a possible
      association with health disparities. There has been consideration to
      therapeutically target EMT in prostate cancer patients by targeting the EMT
      signaling pathways.

PMID- 30229552
TI  - The Role of Multi-Parametric MRI and Fusion Biopsy for the Diagnosis of Prostate
      Cancer - A Systematic Review of Current Literature.
AB  - Introduction The use of mutiparametric MRI (MpMRI) guided fusion biopsy is
      becoming an increasingly popular investigation in an aid to increase diagnostic
      yield in those suspected of having prostate cancer (PCa). Before adopting this
      technology, it is necessary to confirm the accuracy, so that PCa can be reliably
      diagnosed with characterisation. Materials and Methods This chapter analysed the
      evidences, which varied from well-designed randomised controlled trials to case
      series to detect the accuracy of MpMRI compared with biopsy/ histology. Results
      MpMRI incorporating T2 and diffusion weighted imaging only detects tumours in
      around 92% cases. When dynamic contrast enhancement is added, cancer diagnosis is
      significantly improved. Fusion biopsy increases the detection of high-risk PCa by
      32% over conventional biopsy alone. Conclusion This review also revealed that
      fusion biopsy did not increase cancer detection rate but combined biopsy
      (Systematic and fusion) provide the highest detection rate for the diagnosis of
      PCa.

PMID- 30229553
TI  - A Geneticist's View of Prostate Cancer: Prostate Cancer Treatment Considerations.
AB  - Prostate cancer remains a life-threatening disease of men. While early detection
      has been helpful to reduce the mortality rate, we currently do not have a desired
      therapy. In recent years, new strategies have been proposed to treat prostate
      cancers with poor prognosis by utilizing genetically modified bacteria, including
      Salmonella typhimurium that preferentially replicate within solid tumors (1000:1
      and up to 10,000:1 compared to non-cancerous tissue) destroying cancer cells
      without causing septic shock that is typically associated with wild-type S.
      typhimurium infections. Furthermore, these bacteria have the potential to be
      utilized as drug delivery systems to more effectively target different
      subpopulations of prostate tumor cells. This chapter reviews progress in using
      genetically modified S. typhimurium for destruction of prostate tumors.

PMID- 30229554
TI  - Serum progranulin levels are elevated in infertile women with obesity.
AB  - OBJECTIVE: The aim of the present study was to investigate the changes in serum
      progranulin and sex hormone levels in infertile women with obesity. MATERIALS AND
      METHOD: A total of 171 infertile women who have fertility desire were included in
      this cross-sectional study. The initial assessment included the measurements of
      weight, height, waist circumference and hip circumference to calculate body mass
      index (BMI), and waist/hip ratio. All participants were categorized into two
      groups in accordance with BMI as a control group (< 30 kg/m2, n=135), and a study
      group (>= 30 kg/m2, n=36). After anthropometric measurements, venous blood
      samples were taken for analyses of estradiol and follicle stimulating hormone
      (FSH), luteinizing hormone, total testosterone (TT), 17-hydroxyprogesterone,
      dehydroepiandrosterone sulphate, anti-mullerian hormone, and progranulin.
      RESULTS: The present study demonstrated that the normal-weight women had higher
      FSH levels (p<0.01). Elevated TT levels were detected in obese women (p<0.05).
      Progranulin concentrations were higher in the study group than control group
      (p<0.05). Regression analysis demonstrated that there was a relationship between
      the serum progranulin concentrations and BMI (p<0.05). CONCLUSIONS: Our findings
      support that the elevated progranulin levels are associated with obesity in
      infertile women. Therefore, progranulin may be a promising therapeutic target to
      prevent obesity and so infertility.

PMID- 30229555
TI  - Determinants of obesity in population of PURE study from Lower Silesia.
AB  - BACKGROUND: The knowledge about obesity pathogenesis is insufficient. The aim of
      our study was to investigate environmental and individual determinants of obesity
      in population of PURE study from Lower Silesia. MATERIALS AND METHODS: This was a
      cross sectional observation of 1064 inhabitants of Wroclaw and neighbouring rural
      area (671 women, 393 men), who took part in PURE study in years 2007-2010. Each
      participant answered PURE questionnaire and International Physical Activity
      Questionnaire providing information about obesity risk factors. Anthropometric
      measurements were collected, blood samples were taken for assessment of FTO gene
      polymorphism. A stepwise logistic regression analysis was performed to identify
      the most significant predictors of obesity. RESULTS: 31% of the study group had
      obesity (BMI over 30 kg/m2, no difference between men and women), overweight (BMI
      25 - 29.9 kg/m2 ) affected 48.1% of men and 36.7% of women. Determinants of
      obesity in female group were: rural inhabitancy, chronic medication,
      unemployment, age, sedentary leisure time activity, non-smoking, hypertension in
      family, family related stress (p= 0.665287 in the Hosmer-Lemeshow test).
      Determinants of obesity in male group were rural inhabitancy, chronic medication,
      family related stress, diabetes in family (p = 0.272337 in the Hosmer-Lemeshow
      test). Risk factors for central obesity were similar, however in women oral
      contraception and physical activity were associated with lower obesity risk.
      CONCLUSIONS: Environmental factors, especially rural inhabitancy and family
      related stress were associated with higher obesity risk in our study. Employment,
      smoking, physical activity and use of oral contraception seemed to have
      protective role in women.

PMID- 30229556
TI  - Pleistocene diversification in an ancient lineage: a role for glacial cycles in
      the evolutionary history of Dioon Lindl. (Zamiaceae).
AB  - PREMISE OF THE STUDY: Recent estimates of crown ages for cycad genera (Late
      Miocene) challenge us to consider what processes have produced the extant
      diversity of this ancient group in such relatively little time. Pleistocene
      climate change has driven major shifts in species distributions in Mexico and may
      have led to speciation in the genus Dioon by forcing populations to migrate up in
      elevation, thereby becoming separated by topography. METHODS: We inferred
      orthologs from transcriptomes of five species and sequenced these in 42
      individuals representing all Dioon species. From these data and published plastid
      sequences, we inferred dated species trees and lineage-specific diversification
      rates. KEY RESULTS: Analyses of 84 newly sequenced nuclear orthologs and
      published plastid data confirm four major clades within Dioon, all of Pleistocene
      age. Gene tree analysis, divergence dates, and an increase in diversification
      rate support very recent and rapid divergence of extant taxa. CONCLUSIONS: This
      study confirms the Pleistocene age of Dioon species and implicates Pleistocene
      climate change and established topography in lineage spitting. These results add
      to our understanding of the cycads as evolutionarily dynamic lineages, not
      relicts or evolutionary dead ends. We also find that well-supported secondary
      calibration points can be reliable in the absence of fossils. Our hypothesis of
      lineage splitting mediated by habitat shifts may be applicable to other taxa that
      are restricted to elevation specific ecotones.

PMID- 30229557
TI  - Interventions for promoting habitual exercise in people living with and beyond
      cancer.
AB  - BACKGROUND: This is an updated version of the original Cochrane Review published
      in the Cochrane Library 2013, Issue 9. Despite good evidence for the health
      benefits of regular exercise for people living with or beyond cancer,
      understanding how to promote sustainable exercise behaviour change in sedentary
      cancer survivors, particularly over the long term, is not as well understood. A
      large majority of people living with or recovering from cancer do not meet
      current exercise recommendations. Hence, reviewing the evidence on how to promote
      and sustain exercise behaviour is important for understanding the most effective
      strategies to ensure benefit in the patient population and identify research
      gaps. OBJECTIVES: To assess the effects of interventions designed to promote
      exercise behaviour in sedentary people living with and beyond cancer and to
      address the following secondary questions: Which interventions are most effective
      in improving aerobic fitness and skeletal muscle strength and endurance? Which
      interventions are most effective in improving exercise behaviour amongst patients
      with different cancers? Which interventions are most likely to promote long-term
      (12 months or longer) exercise behaviour? What frequency of contact with exercise
      professionals and/or healthcare professionals is associated with increased
      exercise behaviour? What theoretical basis is most often associated with better
      behavioural outcomes? What behaviour change techniques (BCTs) are most often
      associated with increased exercise behaviour? What adverse effects are attributed
      to different exercise interventions? SEARCH METHODS: We used standard
      methodological procedures expected by Cochrane. We updated our 2013 Cochrane
      systematic review by updating the searches of the following electronic databases:
      Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library,
      MEDLINE, Embase, AMED, CINAHL, PsycLIT/PsycINFO, SportDiscus and PEDro up to May
      2018. We also searched the grey literature, trial registries, wrote to leading
      experts in the field and searched reference lists of included studies and other
      related recent systematic reviews. SELECTION CRITERIA: We included only
      randomised controlled trials (RCTs) that compared an exercise intervention with
      usual care or 'waiting list' control in sedentary people over the age of 18 with
      a homogenous primary cancer diagnosis. DATA COLLECTION AND ANALYSIS: In the
      update, review authors independently screened all titles and abstracts to
      identify studies that might meet the inclusion criteria, or that could not be
      safely excluded without assessment of the full text (e.g. when no abstract is
      available). We extracted data from all eligible papers with at least two members
      of the author team working independently (RT, LS and RG). We coded BCTs according
      to the CALO-RE taxonomy. Risk of bias was assessed using the Cochrane's tool for
      assessing risk of bias. When possible, and if appropriate, we performed a fixed
      effect meta-analysis of study outcomes. If statistical heterogeneity was noted, a
      meta-analysis was performed using a random-effects model. For continuous outcomes
      (e.g. cardiorespiratory fitness), we extracted the final value, the standard
      deviation (SD) of the outcome of interest and the number of participants assessed
      at follow-up in each treatment arm, to estimate the standardised mean difference
      (SMD) between treatment arms. SMD was used, as investigators used heterogeneous
      methods to assess individual outcomes. If a meta-analysis was not possible or was
      not appropriate, we narratively synthesised studies. The quality of the evidence
      was assessed using the GRADE approach with the GRADE profiler. MAIN RESULTS: We
      included 23 studies in this review, involving a total of 1372 participants (an
      addition of 10 studies, 724 participants from the original review); 227 full
      texts were screened in the update and 377 full texts were screened in the
      original review leaving 35 publications from a total of 23 unique studies
      included in the review. We planned to include all cancers, but only studies
      involving breast, prostate, colorectal and lung cancer met the inclusion
      criteria. Thirteen studies incorporated a target level of exercise that could
      meet current recommendations for moderate-intensity aerobic exercise (i.e.150
      minutes per week); or resistance exercise (i.e. strength training exercises at
      least two days per week).Adherence to exercise interventions, which is crucial
      for understanding treatment dose, is still reported inconsistently. Eight studies
      reported intervention adherence of 75% or greater to an exercise prescription
      that met current guidelines. These studies all included a component of
      supervision: in our analysis of BCTs we designated these studies as 'Tier 1
      trials'. Six studies reported intervention adherence of 75% or greater to an
      aerobic exercise goal that was less than the current guideline recommendations:
      in our analysis of BCTs we designated these studies as 'Tier 2 trials.' A
      hierarchy of BCTs was developed for Tier 1 and Tier 2 trials, with programme goal
      setting, setting of graded tasks and instruction of how to perform behaviour
      being amongst the most frequent BCTs. Despite the uncertainty surrounding
      adherence in some of the included studies, interventions resulted in improvements
      in aerobic exercise tolerance at eight to 12 weeks (SMD 0.54, 95% CI 0.37 to
      0.70; 604 participants, 10 studies; low-quality evidence) versus usual care. At
      six months, aerobic exercise tolerance was also improved (SMD 0.56, 95% CI 0.39
      to 0.72; 591 participants; 7 studies; low-quality evidence). AUTHORS'
      CONCLUSIONS: Since the last version of this review, none of the new relevant
      studies have provided additional information to change the conclusions. We have
      found some improved understanding of how to encourage previously inactive cancer
      survivors to achieve international physical activity guidelines. Goal setting,
      setting of graded tasks and instruction of how to perform behaviour, feature in
      interventions that meet recommendations targets and report adherence of 75% or
      more. However, long-term follow-up data are still limited, and the majority of
      studies are in white women with breast cancer. There are still a considerable
      number of published studies with numerous and varied issues related to high risk
      of bias and poor reporting standards. Additionally, the meta-analyses were often
      graded as consisting of low- to very low-certainty evidence. A very small number
      of serious adverse effects were reported amongst the studies, providing
      reassurance exercise is safe for this population.

PMID- 30229558
TI  - Rigid motion-corrected magnetic resonance fingerprinting.
AB  - PURPOSE: Develop a method for rigid body motion-corrected magnetic resonance
      fingerprinting (MRF). METHODS: MRF has shown some robustness to abrupt motion
      toward the end of the acquisition. Here, we study the effects of different types
      of rigid body motion during the acquisition on MRF and propose a novel approach
      to correct for this motion. The proposed method (MC-MRF) follows 4 steps: (1)
      sliding window reconstruction is performed to produce high-quality auxiliary
      dynamic images; (2) rotation and translation motion is estimated from the dynamic
      images by image registration; (3) estimated motion is used to correct acquired k
      space data with corresponding rotations and phase shifts; and (4) motion
      corrected data are reconstructed with low-rank inversion. MC-MRF was validated in
      a standard T1 /T2 phantom and 2D in vivo brain acquisitions in 7 healthy
      subjects. Additionally, the effect of through-plane motion in 2D MC-MRF was
      investigated. RESULTS: Simulation results show that motion in MRF can introduce
      artifacts in T1 and T2 maps, depending when it occurs. MC-MRF improved parametric
      map quality in all phantom and in vivo experiments with in-plane motion,
      comparable to the no-motion ground truth. Reduced parametric map quality, even
      after motion correction, was observed for acquisitions with through-plane motion,
      particularly for smaller structures in T2 maps. CONCLUSION: Here, a novel method
      for motion correction in MRF (MC-MRF) is proposed, which improves parametric map
      quality and accuracy in comparison to no-motion correction approaches. Future
      work will include validation of 3D MC-MRF to enable also through-plane motion
      correction.

PMID- 30229559
TI  - Pancreatic perfusion and arterial-transit-time quantification using
      pseudocontinuous arterial spin labeling at 3T.
AB  - PURPOSE: To demonstrate the feasibility of noninvasively measuring pancreatic
      perfusion using pseudocontinuous arterial spin labeling (ASL) and to derive
      quantitative blood-flow and transit-time measurements in healthy volunteers.
      METHODS: A pseudocontinuous ASL sequence with background suppression and a single
      slice single-shot fast-spin-echo readout was acquired at 3 T in 10 subjects with
      a single standard postlabeling delay (PLD) of 1.5 s and in 4 additional subjects
      with 4 PLD from 0.7 to 2 s. An imaging synchronized breathing approach was used
      to minimize motion artifacts during the 3 min of acquisition. Scan-rescan
      reproducibility was assessed in 3 volunteers with single-delay ASL. Quantitative
      blood flow and arterial transit time (ATT) were derived and the impact of ATT
      correction was studied using either subject-specific ATT in the second group or
      an average ATT derived from the group with multidelay ASL for subjects with
      single-delay ASL. RESULTS: Successful ASL acquisitions were performed in all
      volunteers. An average pancreatic blood flow of 201 +/- 40 mL/100 g/min was
      measured in the single-delay group using an assumed ATT of 750 ms Average ATT
      measured in the multidelay group was 1029 +/- 89 ms Using the longer, measured
      ATT reduced the measured flow to 162 +/- 12 and 168 +/- 28 mL/100 g/min with
      subject-specific or average ATT correction, respectively. ASL signal
      heterogeneities were observed at shorter PLD, potentially linked to its complex
      vascular supply and islet distribution. CONCLUSIONS: ASL enables reliable
      measurement of pancreatic perfusion in healthy volunteers. It presents a valuable
      alternative to contrast-enhanced methods and may be useful for diagnosis and
      characterization of several inflammatory, metabolic, and neoplastic diseases
      affecting the pancreas.

PMID- 30229561
TI  - Erratum.

PMID- 30229560
TI  - Wideband myocardial perfusion pulse sequence for imaging patients with a cardiac
      implantable electronic device.
AB  - PURPOSE: To develop a wideband cardiac perfusion pulse sequence and test whether
      it is capable of suppressing image artifacts in patients with a cardiac
      implantable electronic device (CIED), while not exceeding the specific absorption
      rate (SAR) limit (2.0 W/kg). METHODS: A wideband perfusion pulse sequence was
      developed by incorporating a wideband saturation pulse to achieve a good balance
      between saturation of magnetization and SAR. Clinical standard and wideband
      perfusion MRI scans were performed back-to-back in a randomized order on 16
      patients with a CIED undergoing clinical cardiac MRI. Two expert readers graded
      the artifact intensity and extent on a segmental basis using a 5-point Likert
      scale, where significant artifact was defined by a composite score. The variance
      in myocardial signal before tissue-enhancement was analyzed to quantify artifact
      intensity. Whole-body SAR values computed by the MR scanner were read from the
      DICOM header. Either a paired t-test or Wilcoxon signed-rank test was performed
      to compare two groups. RESULTS: While the mean whole-body SAR for a single-slice
      wideband perfusion scan (0.38 +/- 0.08 W/kg) was significantly (P < 0.05) higher
      than for a single-slice standard perfusion scan (0.11 +/- 0.03 W/kg), it was 81%
      below 2.0 W/kg. The mean variance in myocardial signal before tissue-enhancement
      was significantly (P < 0.001) higher for standard (422.6 +/- 306.6 au) than
      wideband (107.0 +/- 60.9 au). Among 105 myocardial segments, standard produced 19
      segments (18%) that were deemed to have significant artifacts, whereas wideband
      produced only 3 segments (3%). CONCLUSION: A wideband perfusion pulse sequence is
      capable of suppressing image artifacts induced by a CIED while not exceeding SAR
      at 2.0 W/kg.

PMID- 30229563
TI  - Prevalence rates of arthritis among US older adults with varying degrees of
      depression: Findings from the 2011 to 2014 National Health and Nutrition
      Examination Survey.
AB  - OBJECTIVE: Arthritis and depressive symptoms often interact and negatively
      influence one another to worsen mental and physical health outcomes. Better
      characterization of arthritis rates among older adults with different levels of
      depressive symptoms is an important step toward informing mental health
      professionals of the need to detect and respond to arthritis and related mental
      health complications. The primary objective is to determine arthritis rates among
      US older adults with varying degrees of depression. METHODS: Using National
      Health and Nutrition Examination Survey 2011 to 2014 data (N = 4792), we first
      identified participants aged >=50 years. Measures screened for depressive
      symptoms and self-reported doctor-diagnosed arthritis. Weighted logistic
      regression models were conducted. RESULTS: Prevalence of arthritis was 55.0%,
      62.9%, and 67.8% in participants with minor, moderate, and severe depression,
      respectively. In both unadjusted and adjusted regression models, a significant
      association between moderate depression and arthritis persisted. There were also
      significant associations between minor and severe depression with arthritis.
      CONCLUSIONS: Arthritis is commonly reported in participants with varying degrees
      of depression. This study highlights the importance of screening for and treating
      arthritis-related pain in older adults with depressive symptoms and the need for
      future geriatric psychiatry research on developing integrated biopsychosocial
      interventions for these common conditions.

PMID- 30229562
TI  - Tilted-CAIPI for highly accelerated distortion-free EPI with point spread
      function (PSF) encoding.
AB  - PURPOSE: To develop a method for fast distortion- and blurring-free imaging.
      THEORY: EPI with point-spread-function (PSF) mapping can achieve distortion- and
      blurring-free imaging at a cost of long acquisition time. In this study, an
      acquisition/reconstruction technique, termed "tilted-CAIPI," is proposed to
      achieve >20* acceleration for PSF-EPI. The proposed method systematically
      optimized the k-space sampling trajectory with B0 -inhomogeneity-informed
      reconstruction, to exploit the inherent signal correlation in PSF-EPI and take
      full advantage of coil sensitivity. Susceptibility-induced phase accumulation is
      regarded as an additional encoding that is estimated by calibration data and
      integrated into reconstruction. Self-navigated phase correction was developed to
      correct shot-to-shot phase variation in diffusion imaging. METHODS: Tilted-CAIPI
      was implemented at 3T, with incorporation of partial Fourier and simultaneous
      multislice to achieve further accelerations. T2 -weighted, T2 * -weighted, and
      diffusion-weighted imaging experiments were conducted to evaluate the proposed
      method. RESULTS: The ability of tilted-CAIPI to provide highly accelerated
      imaging without distortion and blurring was demonstrated through in vivo brain
      experiments, where only 8 shots per simultaneous slice group were required to
      provide high-quality, high-SNR imaging at 0.8-1 mm resolution. CONCLUSION: Tilted
      CAIPI achieved fast distortion- and blurring-free imaging with high SNR. Whole
      brain T2 -weighted, T2 * -weighted, and diffusion imaging can be obtained in just
      15-60 s.

PMID- 30229564
TI  - Relevance of time-dependence for clinically viable diffusion imaging of the
      spinal cord.
AB  - PURPOSE: Time-dependence is a key feature of the diffusion-weighted (DW) signal,
      knowledge of which informs biophysical modelling. Here, we study time-dependence
      in the human spinal cord, as its axonal structure is specific and different from
      the brain. THEORY AND METHODS: We run Monte Carlo simulations using a synthetic
      model of spinal cord white matter (WM) (large axons), and of brain WM (smaller
      axons). Furthermore, we study clinically feasible multi-shell DW scans of the
      cervical spinal cord (b = 0; b = 711 s mm-2 ; b = 2855 s mm-2 ), obtained using
      three diffusion times (Delta of 29, 52 and 76 ms) from three volunteers. RESULTS:
      Both intra-/extra-axonal perpendicular diffusivities and kurtosis excess show
      time-dependence in our synthetic spinal cord model. This time-dependence is
      reflected mostly in the intra-axonal perpendicular DW signal, which also exhibits
      strong decay, unlike our brain model. Time-dependence of the total DW signal
      appears detectable in the presence of noise in our synthetic spinal cord model,
      but not in the brain. In WM in vivo, we observe time-dependent macroscopic and
      microscopic diffusivities and diffusion kurtosis, NODDI and two-compartment SMT
      metrics. Accounting for large axon calibers improves fitting of multi-compartment
      models to a minor extent. CONCLUSIONS: Time-dependence of clinically viable DW
      MRI metrics can be detected in vivo in spinal cord WM, thus providing new
      opportunities for the non-invasive estimation of microstructural properties. The
      time-dependence of the perpendicular DW signal may feature strong intra-axonal
      contributions due to large spinal axon caliber. Hence, a popular model known as
      "stick" (zero-radius cylinder) may be sub-optimal to describe signals from the
      largest spinal axons.

PMID- 30229565
TI  - Accelerated, free-breathing, noncontrast, electrocardiograph-triggered, thoracic
      MR angiography with stack-of-stars k-space sampling and GRASP reconstruction.
AB  - PURPOSE: To develop an accelerated, free-breathing, noncontrast,
      electrocardiograph-triggered, thoracic MR angiography (NC-MRA) pulse sequence
      capable of achieving high spatial resolution at clinically acceptable scan time
      and test whether it produces clinically acceptable image quality in patients with
      suspected aortic disease. METHODS: We modified a "coronary" MRA pulse sequence to
      use a stack-of-stars k-space sampling pattern and combined it with golden-angle
      radial sparse parallel (GRASP reconstruction to enable self-navigation of
      respiratory motion and high data acceleration. The performance of the proposed NC
      MRA was evaluated in 13 patients, where clinical standard contrast-enhanced MRA
      (CE-MRA) was used as control. For visual analysis, two readers graded the
      conspicuity of vessel lumen, artifacts, and noise level on a 5-point scale
      (overall score index = sum of three scores). The aortic diameters were measured
      at seven standardized locations. The mean visual scores, inter-observer
      variability, and vessel diameters were compared using appropriate statistical
      tests. RESULTS: The overall mean visual score index (12.1 +/- 1.7 for CE-MRA
      versus 12.1 +/- 1.0 for NC-MRA) scores were not significantly different (P >
      0.16). The two readers' scores were significantly different for CE-MRA (P = 0.01)
      but not for NC-MRA (P = 0.21). The mean vessel diameters were not significantly
      different, except at the proximal aortic arch (P < 0.03). The mean diameters were
      strongly correlated (R2 >= 0.96) and in good agreement (absolute mean difference
      <= 0.01 cm and 95% confidence interval <= 0.62 cm). CONCLUSION: This study shows
      that the proposed NC-MRA produces clinically acceptable image quality in patients
      at high spatial resolution (1.5 mm * 1.5 mm * 1.5 mm) and clinically acceptable
      scan time (~6 min).

PMID- 30229566
TI  - Computation of exact g-factor maps in 3D GRAPPA reconstructions.
AB  - PURPOSE: To characterize the noise distributions in 3D-MRI accelerated
      acquisitions reconstructed with GRAPPA using an exact noise propagation analysis
      that operates directly in k-space. THEORY AND METHODS: We exploit the extensive
      symmetries and separability in the reconstruction steps to account for the
      correlation between all the acquired k-space samples. Monte Carlo simulations and
      multi-repetition phantom experiments were conducted to test both the accuracy and
      feasibility of the proposed method; a high-resolution in-vivo experiment was
      performed to assess the applicability of our method to clinical scenarios.
      RESULTS: Our theoretical derivation shows that the direct k-space analysis
      renders an exact noise characterization under the assumptions of stationarity and
      uncorrelation in the original k-space. Simulations and phantom experiments
      provide empirical support to the theoretical proof. Finally, the high-resolution
      in-vivo experiment demonstrates the ability of the proposed method to assess the
      impact of the sub-sampling pattern on the overall noise behavior. CONCLUSIONS: By
      operating directly in the k-space, the proposed method is able to provide an
      exact characterization of noise for any Cartesian pattern sub-sampled along the
      two phase-encoding directions. Exploitation of the symmetries and separability
      into independent blocks through the image reconstruction procedure allows us to
      overcome the computational challenges related to the very large size of the
      covariance matrices involved.

PMID- 30229568
TI  - Evidence of the clinical utility of a prolonged grief disorder diagnosis.

PMID- 30229569
TI  - Personality traits and risk of suicide mortality: findings from a multi-cohort
      study in the general population.

PMID- 30229567
TI  - Adrenergic receptor blockade attenuates placental ischemia-induced hypertension.
AB  - Preeclampsia (PE), a disorder of new-onset maternal hypertension and vascular
      dysfunction during pregnancy, is thought to be linked to placental ischemia
      induced release of prohypertensive factors and reductions of vasoprotective
      factors in the maternal circulation. Although markers of sympathetic nervous
      activity are elevated in experimental models of placental ischemia-induced
      hypertension and women with PE compared with their normal pregnant counterparts,
      the importance of adrenergic receptor signaling in the development of
      hypertension in PE is unknown. Therefore, we tested the hypothesis that
      adrenergic receptor blockade attenuates the development of placental ischemia
      induced hypertension in rats. Wistar Hannover rats underwent reduced uterine
      perfusion pressure (RUPP) or Sham surgeries on gestational day 14. By day 19,
      mean arterial blood pressure (MAP) was increased in RUPP over Sham rats. Groups
      of RUPP and Sham pregnant rats received terazosin and propranolol (3 mg/kg per
      day of each via subcutaneous osmotic minipump) to block alpha1- and beta
      adrenergic receptors, respectively, beginning on gestational day 14. Adrenergic
      blockade significantly attenuated the development of hypertension in the RUPP
      rats with a slight blood pressure-lowering response in the Sham, normal pregnant
      rats by day 19. In conclusion, these data implicate that placental ischemia
      induced hypertension involves adrenergic receptor signaling to promote increases
      in blood pressure during PE.

PMID- 30229570
TI  - Insomnia and inflammation: a two hit model of depression risk and prevention.

PMID- 30229574
TI  - Update on the Aldosterone Resolution Score and Lateralization in Patients with
      Primary Aldosteronism.

PMID- 30229572
TI  - Recent Topics in Fibrodysplasia Ossificans Progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease that is
      characterized by the formation of heterotopic bone tissues in soft tissues, such
      as skeletal muscle, ligament, and tendon. It is difficult to remove such
      heterotopic bones via internal medicine or invasive procedures. The
      identification of activin A receptor, type I (ACVR1)/ALK2 gene mutations
      associated with FOP has allowed the genetic diagnosis of FOP. The ACVR1/ALK2 gene
      encodes the ALK2 protein, which is a transmembrane kinase receptor in the
      transforming growth factor-beta family. The relevant mutations activate
      intracellular signaling in vitro and induce heterotopic bone formation in vivo.
      Activin A is a potential ligand that activates mutant ALK2 but not wild-type
      ALK2. Various types of small chemical and biological inhibitors of ALK2 signaling
      have been developed to establish treatments for FOP. Some of these are in
      clinical trials in patients with FOP.

PMID- 30229571
TI  - Progress in achieving quantitative classification of psychopathology.
AB  - Shortcomings of approaches to classifying psychopathology based on expert
      consensus have given rise to contemporary efforts to classify psychopathology
      quantitatively. In this paper, we review progress in achieving a quantitative and
      empirical classification of psychopathology. A substantial empirical literature
      indicates that psychopathology is generally more dimensional than categorical.
      When the discreteness versus continuity of psychopathology is treated as a
      research question, as opposed to being decided as a matter of tradition, the
      evidence clearly supports the hypothesis of continuity. In addition, a related
      body of literature shows how psychopathology dimensions can be arranged in a
      hierarchy, ranging from very broad "spectrum level" dimensions, to specific and
      narrow clusters of symptoms. In this way, a quantitative approach solves the
      "problem of comorbidity" by explicitly modeling patterns of co-occurrence among
      signs and symptoms within a detailed and variegated hierarchy of dimensional
      concepts with direct clinical utility. Indeed, extensive evidence pertaining to
      the dimensional and hierarchical structure of psychopathology has led to the
      formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium.
      This is a group of 70 investigators working together to study empirical
      classification of psychopathology. In this paper, we describe the aims and
      current foci of the HiTOP Consortium. These aims pertain to continued research on
      the empirical organization of psychopathology; the connection between personality
      and psychopathology; the utility of empirically based psychopathology constructs
      in both research and the clinic; and the development of novel and comprehensive
      models and corresponding assessment instruments for psychopathology constructs
      derived from an empirical approach.

PMID- 30229573
TI  - Skeletal Fragility in Type 2 Diabetes Mellitus.
AB  - Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has
      been reported in several epidemiological studies. However, bone mineral density
      in T2D is increased and underestimates the fracture risk. Common risk factors for
      fracture do not fully explain the increased fracture risk observed in patients
      with T2D. We propose that the pathogenesis of increased fracture risk in T2D is
      due to low bone turnover caused by osteocyte dysfunction resulting in bone
      microcracks and fractures. Increased levels of sclerostin may mediate the low
      bone turnover and may be a novel marker of increased fracture risk, although
      further research is needed. An impaired incretin response in T2D may also affect
      bone turnover. Accumulation of advanced glycosylation endproducts may also impair
      bone strength. Concerning antidiabetic medication, the glitazones are detrimental
      to bone health and associated with increased fracture risk, and the
      sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the
      results on the effect of other antidiabetics are ambiguous. No specific guideline
      for the management of bone disease in T2D is available and current evidence on
      the effects of antiosteoporotic medication in T2D is sparse. The aim of this
      review is to collate current evidence of the pathogenesis, detection and
      treatment of diabetic bone disease.

PMID- 30229576
TI  - Iodine Status in Filipino Women of Childbearing Age.
AB  - BACKGROUND: Iodine deficiency (ID) has become a concern not only among pregnant
      women, but in women of childbearing age as well. In fact, a recent report
      suggested that women with moderate to severe ID may experience a significantly
      longer time to conceive. This study aimed to investigate iodine status in
      Filipino women of childbearing age. METHODS: The iodine status of 6,194 Filipino
      women aged 15 to 45 years old was assessed through urinary iodine analysis. A
      casual spot urine sample was collected from women in households participating in
      the eighth National Nutrition Survey conducted by the Food and Nutrition Research
      Institute. The sample was analyzed using ammonium persulfate digestion followed
      by the Sandell-Kolthoff colorimetric reaction. A median urinary iodine
      concentration (UIC) of less than 100 MUg/L was used to define ID. RESULTS: The
      median UIC was 123 MUg/L, indicative of adequate iodine nutrition; however, 21.5%
      of participants had a UIC below 50 MUg/L. The median UIC of women who lived in
      urban areas (142 MUg/L), belonged to the middle to richest class (>124 MUg/L),
      had reached a college education (136 MUg/L), and used iodized salt (15 ppm and
      above; 148 to 179 MUg/L) reflected adequate iodine nutrition. ID was found to
      have been eliminated in the regions of Central Luzon, Eastern Visayas,
      Calabarzon, Mimaropa, and the National Capital, while mild ID was identified in
      Western Visayas, Southern and Western Mindanao, and in the Autonomous Region in
      Muslim Mindanao. CONCLUSION: Pockets of ID among women of childbearing age exist
      in the Philippines. Proper information through education and the use of
      adequately iodized salt are key measures for improving the iodine status of the
      studied population.

PMID- 30229575
TI  - Calpain-10 and Adiponectin Gene Polymorphisms in Korean Type 2 Diabetes Patients.
AB  - BACKGROUND: Genetic variations in calpain-10 and adiponectin gene are known to
      influence insulin secretion and resistance in type 2 diabetes mellitus. Recently,
      several single nucleotide polymorphisms (SNPs) in calpain-10 and adiponectin gene
      have been reported to be associated with type 2 diabetes and various metabolic
      derangements. We investigated the associations between specific calpain-10 and
      adiponectin gene polymorphisms and Korean type 2 diabetes patients. METHODS:
      Overall, 249 type 2 diabetes patients and 131 non-diabetic control subjects were
      enrolled in this study. All the subjects were genotyped for SNP-43 and -63 of
      calpain-10 gene and G276T and T45G frequencies of the adiponectin gene. The
      clinical characteristics and measure of glucose metabolism were compared within
      these genotypes. RESULTS: Among calpain-10 polymorphisms, SNP-63 T/T were more
      frequent in diabetes patients, and single SNP-63 increases the susceptibility to
      type 2 diabetes. However, SNP-43 in calpain-10 and T45G and intron G276T in
      adiponectin gene were not significantly associated with diabetes, insulin
      resistance, nor insulin secretion. CONCLUSION: Variations in calpain-10, SNP-63
      seems to increase the susceptibility to type 2 diabetes in Koreans while SNP-43
      and adiponectin SNP-45, -276 are not associated with impaired glucose metabolism.

PMID- 30229577
TI  - Genetic Analysis of CLCN7 in an Old Female Patient with Type II Autosomal
      Dominant Osteopetrosis.
AB  - BACKGROUND: Type II autosomal dominant osteopetrosis (ADO II) is a rare
      genetically heterogeneous disorder characterized by osteosclerosis and increased
      bone mass, predominantly involving spine, pelvis, and skull. It is closely
      related to functional defect of osteoclasts caused by chloride voltage-gated
      channel 7 (CLCN7) gene mutations. In this study, we aimed to identify the
      pathogenic mutation in a Korean patient with ADO II using whole exome sequencing.
      METHODS: We evaluated the clinical, biochemical, and radiographic analysis of a
      68-year-old woman with ADO II. We also performed whole exome sequencing to
      identify pathogenic mutation of a rare genetic disorder of the skeleton.
      Moreover, a polymorphism phenotyping program, Polymorphism Phenotyping v2
      (PolyPhen-2), was used to assess the effect of the identified mutation on protein
      function. RESULTS: Whole exome sequencing using peripheral leukocytes revealed a
      heterozygous c.296A>G missense mutation in the CLCN7 gene. The mutation was also
      confirmed using Sanger sequencing. The mutation c.296A>G was regarded to have a
      pathogenic effect by PolyPhen-2 software. CONCLUSION: We detect a heterozygous
      mutation in CLCN7 gene of a patient with ADO II, which is the first report in
      Korea. Our present findings suggest that symptoms and signs of ADO II patient
      having a c.296A>G mutation in CLCN7 may appear at a very late age. The present
      study would also enrich the database of CLCN7 mutations and improve our
      understanding of ADO II.

PMID- 30229578
TI  - Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2
      Diabetes Mellitus with Non-alcoholic Fatty Liver Disease.
AB  - BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are expected to
      improve the liver function of patients with non-alcoholic fatty liver disease
      (NAFLD) combined type 2 diabetes mellitus (T2DM) by its characteristic mechanism.
      This study was designed to investigate the effect of dapagliflozin, one of the
      SGLT2i, on the liver function of T2DM with NAFLD when combined with metformin.
      METHODS: Among patients who received dual oral hypoglycemic agents within the 3
      months of diagnosing NAFLD, patients who had abnormal alanine aminotransferase
      (ALT) level (>40 IU/L) were included. Patients were divided into two groups:
      metformin+dapagliflozin group and metformin+dipeptidyl peptidase-4 inhibitors
      (DPP4i) group. Demographic data, biochemical data and the clinical and treatment
      histories of all patients were reviewed. RESULTS: A total of 102 patients were
      included (dapagliflozin group, n=50; DPP4i group, n=52). Dapagliflozin group
      showed more weight loss and more ALT decline than DPP4i group (-2.9 kg vs. -0.4
      kg, P=0.005; -21.1 U/L vs. -9.5 U/L, P=0.008, respectively) and the proportion of
      patients with ALT normalization after treatment was also significantly higher in
      the dapagliflozin group (80.0% vs. 61.5%, P=0.041). The effect of dapagliflozin
      with metformin on ALT normalization remained significant after adjustment for
      confounding variables including body weight loss (odds ratio, 3.489; P=0.046).
      CONCLUSION: ALT improvement was statistically significant in the dapagliflozin
      than the DPP4i when combined with metformin and the result was consistent after
      adjustment for confounding variables including body weight loss.

PMID- 30229579
TI  - Effects of Maternal Iodine Status during Pregnancy and Lactation on Maternal
      Thyroid Function and Offspring Growth and Development: A Prospective Study
      Protocol for the Ideal Breast Milk Cohort.
AB  - BACKGROUND: Iodine is an intrinsic element of thyroid hormone, which is essential
      for childhood growth and development. The Ideal Breast Milk (IBM) cohort study
      aims to evaluate the effects of maternal iodine status during pregnancy and
      lactation on maternal thyroid function, offspring growth and development, and
      offspring thyroid function. METHODS: The IBM cohort study recruited pregnant
      women from Seoul National University Hospital between June 2016 and August 2017,
      followed by enrollment of their offspring after delivery. For the maternal
      participants, iodine status is evaluated by urinary iodine concentration (UIC)
      and dietary records in the third trimester and at 3 to 4 weeks and 12 to 15
      months postpartum. For the child participants, cord blood sampling and UIC
      measurements are performed at birth. At 3 to 4 weeks of age, UIC and breastmilk
      iodine concentrations are measured. At 12 to 15 months of age, growth and
      development are assessed and measurements of UIC, a thyroid function test, and
      ultrasonography are performed. RESULTS: A total of 198 pregnant women in their
      third trimester were recruited. Their mean age was 35.1+/-3.5 years, and 78
      (39.4%) of them were pregnant with twins. Thirty-three (16.7%) of them had a
      previous history of thyroid disease. CONCLUSION: Korea is an iodine-replete area.
      In particular, lactating women in Korea are commonly exposed to excess iodine due
      to the traditional practice of consuming brown seaweed soup postpartum. The study
      of the IBM cohort is expected to contribute to developing guidelines for optimal
      iodine nutrition in pregnant or lactating women.

PMID- 30229580
TI  - Deficiency of Sphingosine-1-Phosphate Reduces the Expression of Prohibitin and
      Causes beta-Cell Impairment via Mitochondrial Dysregulation.
AB  - BACKGROUND: Emerging evidence suggests that sphingolipids may be involved in type
      2 diabetes. However, the exact signaling defect through which disordered
      sphingolipid metabolism induces beta-cell dysfunction remains unknown. The
      current study demonstrated that sphingosine-1-phosphate (S1P), the product of
      sphingosine kinase (SphK), is an essential factor for maintaining beta-cell
      function and survival via regulation of mitochondrial action, as mediated by
      prohibitin (PHB). METHODS: We examined beta-cell function and viability, as
      measured by mitochondrial function, in mouse insulinoma 6 (MIN6) cells in
      response to manipulation of cellular S1P and PHB levels. RESULTS: Lack of S1P
      induced by sphingosine kinase inhibitor (SphKi) treatment caused beta-cell
      dysfunction and apoptosis, with repression of mitochondrial function shown by
      decreases in cellular adenosine triphosphate content, the oxygen consumption
      rate, the expression of oxidative phosphorylation complexes, the mitochondrial
      membrane potential, and the expression of key regulators of mitochondrial
      dynamics (mitochondrial dynamin-like GTPase [OPA1] and mitofusin 1 [MFN1]).
      Supplementation of S1P led to the recovery of mitochondrial function and greatly
      improved beta-cell function and viability. Knockdown of SphK2 using small
      interfering RNA induced mitochondrial dysfunction, decreased glucose-stimulated
      insulin secretion (GSIS), and reduced the expression of PHB, an essential
      regulator of mitochondrial metabolism. PHB deficiency significantly reduced GSIS
      and induced mitochondrial dysfunction, and co-treatment with S1P did not reverse
      these trends. CONCLUSION: Altogether, these data suggest that S1P is an essential
      factor in the maintenance of beta-cell function and survival through its
      regulation of mitochondrial action and PHB expression.

PMID- 30229582
TI  - Response: The Association between Persistent Hypertriglyceridemia and the Risk of
      Diabetes Development: The Kangbuk Samsung Health Study (Endocrinol Metab
      2018;33:55-61, Yu Hyun Kwon et al.).

PMID- 30229583
TI  - [Ratios of Volatile Organic Compounds in Ambient Air of Various Cities of China].
AB  - Volatile organic compounds (VOC) ratios in urban atmosphere could provide
      important information on VOC data quality, sources, and options for removal
      processes. Based on seven VOC measurement datasets, useful VOC ratios were
      calculated using four methods, including orthogonal distance(ODR), linear
      regression, geometric mean, mean, and frequency distribution. Ambient levels of
      m,p-xylene and o-xylene from the seven datasets showed good correlation with r
      ranging from 0.975 to 0.997, and their ratios (m,p-xylene/o-xylene) were close,
      with values of 2.78-3.05, indicating therefore that the ratio of m,p-xylene/o
      xylene could be used to evaluate the quality of ambient measurement data in urban
      atmospheres. In addition, ratios of toluene versus benzene (T/B) and propane
      versus ethane (P/E) in different cities were compared, to investigate VOC sources
      in China. The highest T/B ratios were found in Shanghai and Guangzhou City, with
      values of 2.37 and 1.78, respectively, higher than the result from a tunnel study
      (1.52), suggesting the important influence of paint and solvent use. The T/B
      value for Beijing City during summer was close to that from the tunnel study,
      while the T/B ratios for Chengdu, Beijing during winter, and Chongqing were
      lower, with values ranging from 0.744 to 1.36, suggesting possible influences
      from biomass burning and coal combustion. The P/E value in Guangzhou was 1.27,
      significantly higher than the range of 0.270 to 0.645 found in other cities. The
      OH exposure in different cities were calculated based on o-xylene/ethylbenzene
      (X/E), with values ranging from 2.70*1010 to 4.45*1010 molecule.cm-3.s.

PMID- 30229584
TI  - [Temporal Variation, Spatial Distribution, and Reactivity Characteristics of Air
      VOCs in Beijing 2015].
AB  - In 2015, continuous volatile organic compound (VOC) monitoring was conducted for
      Dongsi (urban site), the southeast boundary site Yongledian, and Dingling
      (background site). The average annual mole fraction of atmospheric VOCs in urban
      areas was(48.93+/-31.03)*10-9, the average annual mole fraction of the southeast
      boundary was (54.55+/-39.64)*10-9, and the average annual mole fraction for the
      background site was(28.25+/-21.26)*10-9. Considering VOC components, alkanes
      occupy the highest proportion, followed by oxygen-containing VOCs, olefins,
      aromatic hydrocarbons, halogenated hydrocarbons, and acetylene. VOC concentration
      was higher in winter, lower in summer, higher at night and lower in the daytime.
      The concentration of acetylene in urban areas was higher in spring, summer and
      autumn, but higher in winter at the southeast boundary site. However, in the
      background, a small amount of direct anthropogenic interference was detectable,
      with the concentration of oxygen VOCs higher at noon and in summer. The species
      with high mole fractions in the VOCs were identified as mainly ethane, acetylene,
      ethylene, acetaldehyde, propane, acetone, n-butane, dichloromethane, and other
      low-carbon substances. The concentrations of benzene and toluene in the high
      carbon group was relatively high. From the toluene/benzene ratio, it was found
      that Beijing VOCs were influenced by many sources other than transportation.
      However, the ratio of ethane/acetylene has been found to be significantly
      dependent on the aging of air mass in Beijing, with the southeast boundary
      particularly affected by movement of the aging air mass. Changes in the ratio of
      isopentane/TVOC showed that high summer temperature enhanced gasoline
      volatilization. The southeastern boundary point of OFP was the highest, followed
      by the urban area, with Dingling lower. The species with greater contribution to
      OFP were ethylene, propylene, acetaldehyde, paraxylene and toluene, with the
      higher mole fraction of alkanes making little contribution to OFP.

PMID- 30229581
TI  - Functional Identification of Compound Heterozygous Mutations in the CYP17A1 Gene
      Resulting in Combined 17alpha-Hydroxylase/17,20-Lyase Deficiency.
AB  - BACKGROUND: We previously reported a patient with congenital adrenal hyperplasia
      (CAH) with compound heterozygous mutations in the cytochrome P450 17A1 (CYP17A1)
      gene. One allele had a p.His373Leu and the other a new p.Glu383fsX36 mutation.
      The aim of this study was to investigate the functional properties of a new
      allele present in a compound heterozygote of CYP17A1. METHODS: To understand how
      p.His373Leu and p.Glu383fsX36 affect P450c17 enzymatic activity, wild type and
      mutant CYP17A1 cDNAs were cloned into flag-tagged pcDNA3 vector and introduced
      into human embryonic kidney cells 293T (HEK293T) cells. Protein expression levels
      of CYP17A1 were then analyzed. And the activities of 17alpha-hydroxylase and
      17,20-lyase of CYP17A1 were evaluated by measuring the conversion of progesterone
      to 17alpha-hydroxyprogesterone and of 17alpha-hydroxypregnenolone to
      dehydroepiandrosterone, respectively. In addition a computer model was used to
      create the three-dimensional structure of the mutant CYP17A1 enzymes. RESULTS:
      Production of the p.His373Leu mutant protein was significantly lower than that of
      the wild type protein, and the p.Glu383fsX36 protein was hardly produced.
      Similarly the enzymatic activity derived from the p.His373Leu mutant vector was
      significantly lower than that obtained from the wild type vector, and little
      activity was obtained from the p.Glu383fsX36 vector. Three-dimensional modeling
      of the enzyme showed that p.His373 was located in region important for heme
      binding and proper folding. Neither the p.His373Leu nor the p.Glu383fsX36 mutant
      protein formed a heme-binding structure. CONCLUSION: Enzyme activity measured in
      both mutants disappeared completely in both 17alpha-hydroxylase and 17,20-lyase.
      This result accounts for the clinical manifestations of the patient with the
      compound heterozygous CYP17A1 mutations.

PMID- 30229585
TI  - [Research and Application of the Technical Method for the Compilation of VOCs
      Emission Inventories from Architectural Coatings in Beijing].
AB  - VOCs(volatile organic compounds) are important precursors of ozone and secondary
      organic aerosols in the atmosphere, which increase atmospheric oxidation,
      creating pollutants such as photochemical smog, fine particulate matter and so
      on. This study documented information about architectural coating VOC emission
      characteristics to facilitate formulation of control strategies by environmental
      management departments. This research was based on measured data for
      architectural wall and waterproof coatings to identify localized emission
      factors, used industry research to compile additional information, and was
      combined with the Beijing completed building inventory, to develop a compilation
      method for VOC emissions from architectural coatings. According to the above
      research to estimate VOC emissions of the interior wall, exterior wall and
      waterproof coatings in 2015, analysis of the spatial distribution of VOCs was
      performed and VOC emissions were estimated under two conditions regarding whether
      to limit the content of hazardous substances in architectural coatings from 2002
      2015. The results show that 1VOC emissions from the Beijing architechtural wall
      and waterproof coating was about 6914.2t.a-1 in 2015. The emissions from wall
      paint and waterproof coating were 2394.9 t.a-1and 4519.3 t.a-1, accounting for
      34.6% and 65.4%, respectively. 2The spatial distribution of VOC emissions showed
      that emissions were mainly concentrated around the new cities being developed in
      the Chaoyang and Tongzhou districts. The district with the highest VOC emission
      is Tongzhou District, where the proportion of emission is about 13.2%. Following
      it are the Changping and Chaoyang districts, respectively, at 11.8% and 10.5%.
      3In 2015, because of implementation of the standards < Indoor decorating and
      refurbishing materials-Limit of harmful substances of interior architectural
      coatings > (GB 18582-2008) and < Limit of harmful substances of exterior wall
      coatings > (GB 24408-2009), compared to the no control scenario, the VOCs
      emissions under control scenario was one where VOCs emissions were reduced by
      8954.2 t. 4It follows that environmental management and control of the hazardous
      substance contents of architectural coatings can effectively control the VOC
      emission in China.

PMID- 30229586
TI  - [Content Levels and Compositions Characteristics of Volatile Organic
      Compounds(VOCs) Emission from Architectural Coatings Based on Actual
      Measurement].
AB  - The content levels and composition characteristics of Volatile Organic Compounds
      (VOCs) from architectural coatings including interior wall coatings, exterior
      wall coatings, waterproofing coatings, anticorrosive coatings and floor coatings
      were investigated in this study. Architectural coating samples were obtained from
      manufacturers and retail outlets and the associated VOC contents and compositions
      were determined based on the domestic standard methods for measurement of VOCs in
      architectural coatings.The results showed that the VOC contents were 0-145 g.L-1
      and 0-171 g.L-1 for interior and exterior wall coatings respectively. The
      proportion of samples that met the standards of HJ 2537-2014 were 90%, 80%, 96%
      and 94% for interior wall finishing coats, interior wall primary coats, exterior
      wall finishing coats and exterior wall primary coats respectively.The VOC content
      was found to be less than 10 g.L-1 for more than 90% of polymer-cement based
      waterproof coatings and acrylate polymer emulsion waterproof coatings
      respectively, and 1-324 g.L-1 for polyurethane waterproof coatings. The VOC
      contents for solvent-based coatings were found to be generally high, with VOC
      contents ranging from between 291-681 g.L-1 and 16-580 g.L-1 for solvent-based
      anticorrosive coatings and solvent-based floor coatings respectively, with great
      variation shown between different compositions and brands. The 1,2-propanediol
      and ethylene glycol were the most VOC in water-based coatings with methanol and 2
      amino-2-methyl-1-propanol equal second. The main VOCs in solvent-based coatings
      were toluene, ethyl benzene, xylenes (total), ethyl acetate, butyl acetate and
      isobutyl acetate.

PMID- 30229587
TI  - [Characteristics of Primary Pollutants of Air Quality in Cities Along the Taihang
      Mountains in Beijing-Tianjin-Hebei Region During 2014-2016].
AB  - Primary pollutants of air quality in Beijing, Baoding, Shijiazhuang, Xingtai, and
      Handan cities along the Taihang Mountains were analyzed to investigate their
      spatial distribution characteristics and temporal variation trends during 2014
      2016. The results showed that the primary pollutants were ranked as PM2.5, O3-8h,
      NO2 and PM10 from most to least important in Beijing, and PM2.5, PM10, O3-8h,
      NO2, SO2 and CO in the other four cities. Three-year average percentages of days
      with PM2.5 as the primary pollutant in each city were similar (53.3%-58.1%),
      however, percentages of days with PM10 as primary pollutant increased, while
      percentages of O3-8h decreased basically, from north to south. Except for Handan
      with a significant descending trend, percentages of days with PM2.5 as primary
      pollutant varied slightly in the other four cities during the study period, and
      percentages of O3-8h of Shijiazhuang, Xingtai and Handan increased significantly
      in 2016. Percentages of NO2 slightly declined year by year in Beijing, and the
      other four cities mainly showed the opposite trend. Monthly variation curves of
      days with PM2.5 and O3-8h as primary pollutants showed "W" and "inverted U" types
      respectively, while the high value interval of days with PM10 as primary
      pollutant occurred between March and May. With the exception of Beijing, peak of
      monthly variation curves for days with NO2 as the primary pollutant was occurred
      in October in the other four cities. From "moderate" to "hazardous" levels for
      air quality, the percentages of days with PM2.5 and/or PM10 as primary pollutants
      increased level by level, with percentages of PM10 trending downwards and PM2.5
      upwards. Meanwhile, days with O3-8h as the primary pollutant mostly appeared in
      the range between "moderate" and "unhealthy" levels, and NO2 was only prominent
      in "moderate" level.

PMID- 30229588
TI  - [Seasonal Variation and Source Analysis for PM2.5, PM1 and Their Carbonaceous
      Components in Beijing].
AB  - Atmospheric particulate matter is the primary pollutant affecting the ambient air
      quality in most Chinese cities. In recent years, with the progress of monitoring
      technology and improvement in sampling equipment, the relevant research objects
      gradually shift from larger particle sizes (PM10 and PM2.5) to smaller particle
      size (PM1). The carbonaceous component is an important part of atmospheric
      particulate matter. Taking Beijing as the research area, sampling for PM2.5 and
      PM1 was conducted in July and October of 2016, and January and April of 2017 as
      representative months of four seasons. Mass concentrations and seasonal variation
      characteristics for PM2.5 and PM1 were analyzed. The two-layer, nested,
      meteorology-air quality coupling model system (WRF-CMAQ) was used to model air
      circulation during the sampling period and thus analyze the source contributions
      for PM2.5 and PM1. The factor analysis method was also used to analyze the source
      apportionment of carbonaceous components. The results are as followed:the mass
      concentrations of PM2.5 and PM1 showed an increasing trend by spring, summer,
      autumn and winter. PM1 was the main part of PM2.5, and with the increasing
      frequency of haze in autumn and winter, the mass concentration ratio of PM1/PM2.5
      became significantly higher. The authors contend that secondary pollution exists
      in Beijing's atmosphere, and SOC is more likely to accumulate in smaller particle
      size. Widespread coal combustion, vehicle emission, residential emission source
      and biomass combustion emissions are the major contributors to atmospheric
      particulates, while gasoline engine exhaust, diesel vehicle exhaust, biomass
      combustion and coal combustion emission are the main source of carbonaceous
      components in PM2.5 and PM1 in Beijing.

PMID- 30229589
TI  - [Chemical Constitution and Carbon Isotopic Compositions of PM2.5 in the Northern
      Suburb of Nanjing in Spring].
AB  - PM2.5 is an important atmospheric pollution component and has a complicated
      composition. The chemical constitution of PM2.5 in Nanjing northern region during
      March 2016 was analyzed using the Dinoex ICS-3000 and ICS-2000 ion chromatograph
      and DRI Model 2001A thermal/optical carbon analyzer, and the carbon isotopic
      compositions were analyzed using EA-IRMS from Thermo Scientific in order to
      explore pollution behaviors and source apportionment of PM2.5. The results showed
      that the mean concentration of atmospheric PM2.5 was (106.16+/-48.70) MUg.m-3,
      which equated with heavy pollution. Meanwhile, 88% of the samples exhibited the
      presence of the secondary organic pollutants. The average concentration of
      secondary organic carbon (SOC) was (3.58+/-2.78) MUg.m-3 and this high
      concentration was attributed to the reaction of O3 with atmospheric hydrocarbons
      under ultraviolet light on sunny days. In addition, delta13CTC in PM2.5 ranged
      from -26.560/00 to -23.750/00 and the mean was (-25.470/00+/-0.630/00). Combining
      the various analyses, we concluded that atmospheric PM2.5 for the study area was
      mainly derived from coal combustion, vehicle exhaust, geology (natural sources)
      and biomass burning.

PMID- 30229590
TI  - [Analysis of Non-polar Organic Compounds in PM2.5 by Rapid Thermo-desorption
      Method Coupled with GC/MS].
AB  - Non-polar organic compounds (NPOCs) associated with PM2.5 in the atmosphere were
      analyzed by automated thermo-desorption (TD) coupled with gas chromatography/mass
      spectrometry (TD-GC/MS). The analyses for a total of 72 NPOCs were reviewed,
      including 34 PAHs, one Debenzothiophene, 27 alkanes (C10-C34), 5 hopanes and 5
      steranes. Through this improved TD method, operation of filter loadings, TD
      condition and sample introduction were optimized. The MDL were 0.01-1.0, 0.1-8.0
      and 0.50-2.0 ng.m-3 for PAHs, alkanes, hopanes and steranes, respectively.
      Calibration curve linearities were above 0.9 for all compounds. The TD
      efficiencies were 95%-100% for PAHs, 81%-100% for alkanes and 83.1%-100% for
      hopanes and steranes. PM2.5 samples were pretreated by TD and ultrasonic
      extraction methods separately and analyzed by GC/MS in two laboratories. Results
      from these two methods were comparable, as the relative biases were less than 30%
      for most compounds. Analysis results of PM2.5 samples from Linan and Shanghai
      showed that NPOCs were higher in winter than that in summer. Alkanes were
      predominant among NPOCs, followed by PAHs. Source analysis by PAH characteristic
      ratios indicated that fossil fuel burning and coal burning were the main sources
      of NPOCs in the two sites during the sampling periods.

PMID- 30229592
TI  - [Hybrid Electric Bus SCR System Operation and NOx Emission Characteristics Based
      on Remote Communication Technology].
AB  - The selective catalytic reduction system (SCR) is an essential method to reduce
      NOx emissions from heavy-duty diesel engine-powered vehicles, which include
      conventional diesel buses and diesel-electric hybrid buses. Using wireless remote
      communication technology, the SCR system status and NOx emissions were reviewed
      for ten fully-operational hybrid buses from Hangzhou China in this research.
      Under the internal combustion engine mode, the main factors studied were vehicle
      speed, engine operation conditions and environment temperature, impact on the SCR
      catalyst outlet temperature and NOx concentration and dosing rate of the urea
      injector of the SCR system. The research result shows that (32.4+/-4)% of the
      operational time of the hybrid buses with SCR system was spent in internal
      combustion engine mode, and under (26.9+/-11)% of the operation time of this
      mode, the SCR system did not dose urea. The average NOx emission reduction rate
      of the SCR system, when operating normally with hybrid buses, is about 59%. The
      main reasons for the high NOx emission of the diesel-electric hybrid buses in
      operation condition are poor satisfaction of the requirements of the SCR system
      control strategy and the SCR catalyst's low temperature conversion efficiency.
      Whenever the speed of the hybrid buses was above 40 km.h-1, the SCR catalyst
      outlet temperatures were higher than the 230C, and the NOx emission
      concentrations were significantly reduced, as the urea injector working
      proportion and urea quantity increased. In the winter, the SCR catalyst outlet
      temperature and urea injection quantity dropped with the reduced environment
      temperature, which led to increased NOx emissions.

PMID- 30229591
TI  - [Association Between Fine Particulate Matter and Asthma Hospital Outpatient
      Visits in Hangzhou].
AB  - To study the short-term effects of air pollution on asthma visits and differences
      in susceptibility to various groups of people, data for asthma visits from
      January 1, 2013 to December 31, 2015 were obtained from a Hangzhou hospital.
      Considering the nonlinear relationships among concentration of air pollutants,
      respiratory hospital outpatient visits and meteorological factors, Generalized
      Additive Models (GAM) and stratification analysis were used to explore the lag
      effects and differences in people stratifications. The natural cubic spline
      function was used for smoothing the average temperature, the average relative
      humidity and the long-term trend, using dummy variables to control the effect of
      the day of the week and of holidays. Correlation of PM2.5, NO2 and SO2 daily mean
      concentrations were significant (under 0.01) in Spearman correlation analysis,
      while the correlations of daily mean temperature and 3 pollutants were
      significantly negative. The lag effects of PM2.5 concentration on outpatient
      visits of asthma peaked at 3-5 days. The relative risk of asthma reached maximum
      at lag day 5 as 1.0056 (95% CI:1.0021-1.0091), with per 10 MUg.m-3 increment of
      PM2.5 concentration. The relative risk of asthma outpatient visits of all groups
      of patients were statistically significant (P<0.05). The relative risk of asthma
      outpatient visits of males and young and middle-aged group were statistically
      significant at lag days 3-5, and for females and the elderly, were statistically
      significant at lag day 5. With the introduction of the effects of NO2, the
      relative risk of asthma outpatient visits increased at lag 5 day in co-pollutant
      models. The authors concluded that the increase of PM2.5 may be related to the
      increase of asthma hospital outpatient visits within 3-5 days in Hangzhou, and
      the effects on male group and elderly group were more definite.

PMID- 30229593
TI  - [Selection of Priority Contaminants in a Watershed Using Risk Ranking
      Methodology].
AB  - The present study focuses on the risk rankings of different contaminants from
      Daling River in Liaoning Province, China, for categorizing the environmental risk
      levels in the river. Eighteen surface water samples were collected from Daling
      River, which has been polluted by the surrounding fluorine industries for years.
      Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and heavy
      metals were analyzed, and relevant eco-toxicity data obtained from literatures
      were considered. The median concentrations of PFOS and PFOA were observed as 0.77
      3.57 ng.L-1 and 82.93-344 ng.L-1, respectively, which were lower than the
      standard limits of the United Kingdom. The concentrations of heavy metals and
      organochlorine pesticides (OCPs) were found to be lower than level IV of the
      Chinese national environmental quality standards for surface water. The maximum
      concentrations of mercury (Hg) and arsenic (As) were higher than the standard
      level III. The environmental risks ranged from 1.42*10-6 to 2.3*10-2. The order
      of the risks by potential environmental contaminants was Cu > Zn > As > p,p'-DDE
      > p,p'-DDT > Cd > Pb > Hg > PFOA > gamma-HCH > Cr > Ni > alpha-HCH > PFOS. The
      present findings revealed that the environmental risks of PFOS and PFOA were
      relatively low and these were not taken as priority contaminants, but the
      accumulation risks could not be overlooked for a long time. Among the
      contaminants, copper (Cu) was the priority contaminant of Daling River. Hence,
      necessary measures are recommended to reduce the potential effects of
      contaminants on the environment.

PMID- 30229594
TI  - [Characteristics and Sources of Atmospheric Inorganic Nitrogen Wet Deposition in
      Xueyu Cave Watershed, Outer Suburbs of Chongqing City].
AB  - Xueyu Cave watershed is located in Fengdu County in the outskirts of Chongqing,
      where rainfall events were monitored continuously from July 2015 to December
      2017. We explored the variation of mass concentration of atmospheric dissolved
      inorganic nitrogen (NH4+-N and NO3--N), and quantitatively calculated its wet
      deposition fluxes, then the sources of NH4+-N and NO3--N were tracked using the
      Xueyu cave air mass backward trajectory model. The results showed that:1During
      the monitoring period, the average annual dissolved inorganic nitrogen (DIN)
      deposition in the watershed was 14.25 kg.(hm2.a)-1, of which NH4+-N and NO3--N
      were 7.72 kg.(hm2.a)-1 and 6.53 kg.(hm2.a)-1, accounting for 54% and 46% of DIN
      wet precipitation, respectively, and indicating that NH4+-N is the dominant
      species, followed by NO3--N; 2DIN wet deposition flux and concentration showed
      marked seasonal changes. The DIN wet deposition flux in spring and summer was 50%
      higher than that in autumn and winter, while the DIN concentration of wet
      deposition in autumn and winter was 30% higher than those in spring and summer.
      3NH4+-N/NO3--N was between 0.29 and 2.27, and NH4+-N/NO3--N > 1 during the rainy
      season (April to October) and NH4+-N/NO3--N < 1 during the dry season (November
      to March), indicating that the main sources of DIN wet deposition results from
      agricultural activities in the rainy season, and urban contributions in the dry
      season. 4In the study area, the southeastern winds are dominant in the rainy
      season but southwestern winds are dominant in the dry season. These determine the
      sources of DIN wet deposition (agricultural or urban).

PMID- 30229595
TI  - [Characteristics of Nitrogen Deposition in Heilongjiang Liangshui National Nature
      Reserve].
AB  - To investigate the nitrogen deposition status in Heilongjiang Liangshui National
      Nature Reserve, a G78 nitrogen deposition collector was used to monitor dry
      particulate nitrogen deposition and wet nitrogen deposition during the growing
      season in 2015, and a bucket was used to monitor bulk nitrogen deposition during
      non-growing season. The results showed that:1Total nitrogen deposition (wet
      nitrogen deposition+dry particulate nitrogen deposition during the growing season
      and bulk deposition during the non-growing season) was 12.93 kg.(hm2.a)-1,
      inorganic nitrogen deposition was 8.27 kg.(hm2.a)-1 with NH4+/NO3- ratio of 1.3;
      organic nitrogen deposition was 4.66 kg.(hm2.a)-1, which was equivalent to 36.0%
      of the total nitrogen deposition. 2Total nitrogen deposition in the growing
      season (wet+dry particulate deposition) and non-growing season (bulk deposition)
      were 11.42 kg.hm-2 and 1.51 kg.hm-2respectively, which account for 88.3% and
      11.7% of the total nitrogen deposition respectively. 3Total wet nitrogen
      deposition during the growing season was 9.28 kg.hm-2, contributing to 81.3% of
      the total nitrogen deposition in the growing season, and was positively
      correlated with precipitation (R2=0.87, P<0.001); total dry particulate nitrogen
      deposition in the growing season was 2.14 kg.hm-2, which was 18.7% of the total
      nitrogen deposition in growing season. Wet nitrogen deposition in this region is
      moderate compared with other regions in China, and is significantly affected by
      precipitation. There is a potential risk of environmental pollution in this
      region. Thus, environmental protection and water quality monitoring are required
      in the process of production.

PMID- 30229596
TI  - [Key Production Process of Nitrous Oxide and Nitrogen Sources in Tuojia River].
AB  - The nitrogen (N) pollution of water is a common global problem. To understand the
      key production process of N2 O and identify the dominant N sources, Tuojia River,
      a typical agricultural watershed in a subtropical area, was investigated. To
      analyze the characteristics of dual nitrate isotopes (delta15N-NO3-,delta18O-NO3
      ) in water, and N isotope (delta15Norg) and carbon-nitrogen ratio (C/N) in
      sediment organic matter from four reaches(S1-S4), the stable isotopes method was
      used. The results showed that the sources of nitrate varied significantly among
      river segments and were affected by agricultural production and human habitation
      on the land surface. The average delta15N-NO3- in reaches S1, S2, S3, and S4 were
      1.720/00, 2.620/00, 4.100/00, and -1.280/00, respectively, while the average
      delta18O-NO3- were 2.600/00,-0.060/00, 0.850/00, and -0.620/00. The N in
      terrestrial soil made a large contribution to nitrate sources in reach S1, while
      soil N, ammonium N fertilizer, and manure played a main role in reaches S2 and
      S3. Most of the nitrate came from ammonium N fertilizer in reach S4. We also
      found that delta15Norg in sediment organic matter ranged from -0.690/00 to
      11.210/00, and C/N was between 7.30 and 12.02. The mean delta15Norg in reaches S1
      S4 were 1.910/00, 2.960/00, 4.720/00, and 3.230/00, respectively, and the mean
      C/N values were 10.62, 8.63, 9.05, and 9.22, respectively. Although there were
      some differences in delta15Norg among reaches S2-S4, the dominant N source was
      sewage in those reaches. However, soil organic matter was the main N source in
      the sediments of reach S1. The mean delta18O-NO3- in reaches S1-S4 were 
      7.010/00,-0.170/00,-0.280/00, and -0.600/00, respectively, indicating that
      nitrification was the key N2 O production process in these reaches. The ratios of
      delta15N-NO3- and delta18O-NO3- were 0.66,-41.01,-30.23, and 9.39 in reaches S1
      S4, respectively. Finally, we found that there was a positive correlation between
      NO3--N and delta15N-NO3-. To summarize, the N transformation and N2 O production
      could be dominated by the nitrification process in Tuojia River.

PMID- 30229597
TI  - [Impact of Biochar on Nitrogen Removal and Nitrous Oxide Emission in Aerated
      Vertical Flow Constructed Wetland].
AB  - In an intermittent aerated vertical flow constructed wetland, the dissolved
      oxygen (DO) distribution tends to be inhomogeneous because of poor diffusivity
      resulting in the production and emission of nitrous oxide (N2O). As a
      multifunctional environmental material with numerous porosities and a large
      specific area, biochar has been recently applied to enhance pollutant removal and
      reduce greenhouse gas emissions in traditional wetland systems. Using the
      conventional aerated vertical flow constructed wetlands (CW) as the comparison,
      biochar-amended wetland microcosms (SW) were built in greenhouses to investigate
      the influence of biochar on nitrogen removal and N2O emissions. The results
      showed that DO concentration in the aeration stage increased by 0.42 mg.L-1 in
      SW. Furthermore, SW achieved higher removal efficiencies for NH4+-N (99.5%) and
      total nitrogen (TN; 95.0%) than CW. Similar removal rates of chemical oxygen
      demand (COD), close to 94%, were observed in CW and SW, indicating that no
      significant effects resulted from adding biochar (P>0.05). Additionally, N2O
      emission fluxes of CW and SW were 0.92 mg.(m2.h)-1 and 0.27 mg.(m2.h)-1,
      respectively. The N2O cumulative emission in SW was 6.58 mg.m-2, which was
      significantly lower than that in CW (22.03 mg.m-2). Biochar addition could be an
      effective strategy to promote nitrogen removal and reduce N2O emissions.

PMID- 30229598
TI  - [Physiological Responses of Ryegrass in Cadmium-Nonylphenol Co-contaminated Water
      and the Phytoremediation Effects].
AB  - Physiological responses of ryegrass in cadmium-nonylphenol (Cd-NP) co
      contaminated water, as well as the phytoremediation effect were studied under
      laboratory conditions. The experiment revealed that the biomass and chlorophyll
      content of ryegrass significantly declined at high concentrations of Cd2+(10 mg.L
      1), while POD and PPO activities significantly increased. No significant changes
      to the biomass, chlorophyll content and MDA of ryegrass were observed in the
      presence of NP. POD activities significantly increased at high concentrations of
      NP (5 mg.L-1). The addition of high NP concentrate reduced the inhibition of Cd
      under co-contaminated stress, the MDA content and PPO activities both reduced.
      The experiment also revealed that the removal rate of Cd2+ by ryegrass reached
      55.3% after 12 h. The absorption efficiency was improved by high NP
      concentration. Absorption efficiency of Cd2+ by the subterranean part of the
      plant significantly increased in presence of NP, and the absorption efficiency
      increased with the increase of NP concentration. The absorption rate of NP was
      44.6% after 24 h at NP concentration of 5 mg.L-1. The removal rate was slightly
      influenced at low concentrations of Cd2+, but significant inhibition of
      absorption and degradation was observed at high concentrations of Cd2+.

PMID- 30229600
TI  - [Seasonal Variations of DOM Spectral Characteristics in the Surface Water of the
      Upstream Minjiang River].
AB  - Alpine wetlands and valleys of northwestern Sichuan are the main catchment areas
      of Minjiang River, where dissolved organic matter (DOM) in surface waters comes
      mainly from the natural background environment. Sources and structure parameters
      of DOM are important for calibrating the flux and pattern of organic carbon
      exports from plateau wetlands and alpine rivers. In this study, surface water
      samples along the upstream Minjiang River were collected at the end of dry season
      (April) and rainy season (October). Excitation emission matrix (EEM) fluorescence
      spectroscopy coupled with parallel factor analysis (PARAFAC) was used to
      characterize seasonal variations of DOM along Minjiang River. Results showed
      fluorescence peaks (humic-like peaks A and C, protein-like peaks B and T) were
      different along the river. Peak A and peak C were more obvious at the end of dry
      season, while peak B and peak T were more obvious at the end of rainy season.
      PARAFAC produced a three-component model including two humic-like components[C1
      (250-260/380-480 nm) and C2 (300-330/380-480 nm)] and one protein-like
      component[C3 (270-280/300-350 nm)], accounting relative intensity 48.68%-65.02%
      for C1, 23.17%-29.83% for C2, and 11.83%-21.53% for C3. Fluorescence components
      showed variations along the river more prominently in April than October, in
      which the most significant one was C1. Average fluorescence index (FI) values
      ranged from 1.4 to 1.9, indicating that DOM consisted of both autochthonous and
      allochthonous components. Moreover, higher degrees of humification, aromaticity
      and hydrophobicity were found in April than those in October, suggesting more
      terrigenous sources at the end of dry season and more biological sources at the
      end of rainy season. Additionally, chromophoric dissolved organic matter
      (CDOM)[a(355)] correlated significantly with humic-like substance[Fn(355)], which
      also indicated that DOM components originated from terrigenous input in the
      upstream Minjiang River. The results also showed significant positive correlation
      between C1 and C2 in April, with no significant correlation in October, which
      further proved that exogenous input and seasonal variations characterized DOM
      sources in the upstream Minjiang River.

PMID- 30229599
TI  - [Analysis of Absorption Characteristics of Urban Black-odor Water].
AB  - The urban black-odor water body has become a serious problem of urban water
      environment and identifying their optical characteristics in urban areas is the
      prerequisite and basis for their detection by remote sensing. A total of 85
      samples of urban black-odor water, from Changsha, Nanjing, and Wuxi, were
      collected from 2016 to 2017, and a total of 80 samples were collected from non
      black-odor (smelly) water samples. The water quality parameters such as suspended
      matter and the absorption coefficient were measured. The results showed that:1The
      total black-odor water body particulate matter absorption coefficients and non
      pigmented particulate matter absorption coefficients were generally higher than
      those for non-black-odor water bodies and they had a certain degree of
      discrimination at 440 nm, but their effect was not significant. The absorption of
      relatively high levels of particulate matter in black-odor water was mainly due
      to high absorption of non-pigmented particles. In the data collected, non
      pigmented particles in black-odor water accounted for more than 50% of the total
      particles. 2 The Colored Dissolved Organic Matter (CDOM) absorption coefficients
      for black-odor water bodies and non-black-odor water bodies differed. The average
      absorption coefficient of CDOM at 440 nm for black-odor water bodies was 1.7
      times higher than that for non-black-odor water bodies. Thus, the black-odor
      water body can be distinguished by using the slope of the absorption coefficient
      curve fitted in the characteristic wavelength band of 440 nm, as well as in
      different wavelength bands; the overall effect is good. However, as the
      wavelength increases, the discrimination effect decreases. Analysis of the
      absorption characteristics of urban black-odor water bodies will provide
      effective technical support for their detection by remote sensing and
      supervision, and the density of CDOM in black-odor water was generally high,
      which could be used as an important reference for identification.

PMID- 30229601
TI  - [Water Quality and Three-Dimensional Fluorescence of Stormwater Runoff from Lined
      Bioretention Field Cells].
AB  - Bioretention cells have become one of the most popular devices in urban
      stormwater runoff management for their high efficiency in reducing runoff volume
      and pollution loads. However, bioretention cells are unstable in nutrient
      pollutant removal, as is verified by many cases, especially at low temperatures.
      Dissolved organic matters (DOMs) plays an important role in denitrification, but
      the three-dimensional fluorescence characteristics of stormwater runoff in
      bioretention field cells are poorly understood, so to improve the performance of
      bioretention cells in nutrient pollutants control, the authors determined that it
      was necessary to clarify the characteristics of three-dimensional fluorescence of
      stormwater runoff from bioretention cells and explain their relationship to water
      quality. To be applicable to urban landuse in mountainous cities, two field lined
      bioretention cells were constructed, and, from March to April in 2017, while
      temperatures were still low, water quality and three-dimensional fluorescence of
      stormwater runoff were analyzed during low rainfall intensity precipitation
      events. Analysis results showed that the effluent pollutant concentrations had
      low fluctuation after purification by the bioretention cells, and both cells
      showed relatively stable removal rates for NH4+-N and total phosphorus (TP; i.
      e., 78.38%-95.03% and 72.04%-76.04%, respectively). Analysis of fluorescence
      spectra showed that the DOMs in the runoff from the two cells was mostly made up
      of protein and humic substances, mainly of biological origin or aquatic bacterial
      metabolites. Both cells performed well in the removal of protein at I, protein at
      II and fulvic acid (i. e., the removal rates could reach 57.33%-61.30%, 29.82%
      31.28%, and 35.55%-43.16% respectively). Correlation analyses between water
      quality and DOM showed that total Nitrogen (TN), TP and total organic carbon
      (TOC) were positively correlated with the protein content in runoff from the
      biorentention cells, while NO3--N and NH4+-N were negatively correlated with
      protein content. Meanwhile, TN was negatively correlated with DOMs in regions IV
      and V of the cells.

PMID- 30229602
TI  - [Nitrate-Nitrogen Pollution Sources of an Underground River in Karst Agricultural
      Area Using 15N and 18O Isotope Technique].
AB  - The objectives of this study were to reveal the sources of nitrate and the ratio
      of karst in an agricultural basin based on a 15N and 18O isotope technique and
      quantitative calculation of the IsoSource model. From May to October 2017, six
      sampling points in the Qingmuguan river basin, Chongqing, were monitored every 24
      d. Results showed that there was a great risk of nitrate pollution in the
      underground river system, because most NO3--N concentrations of the sampling
      points exceeded the threshold. Spatially, NO3--N concentrations in the
      underground river increased from upstream to downstream. Temporally, NO3--N
      concentrations of Fishpond and Yankou Ponor upstream and Jiangjia Spring
      downstream were impacted by agricultural fertilizer from May to June and
      fluctuated from June to September due to precipitation. With decreased
      agricultural activities, NO3--N concentrations gradually decreased after
      September. NO3--N concentrations were high in midstream soil water. Daluchi, in
      the middle and lower reaches, maintained relatively low NO3--N concentrations
      with stable fluctuations. Dual 15N and 18O isotopic compositions suggested that
      the upstream nitrates were derived from soil organic nitrogen and a mixture of
      manure and sewage. The midstream nitrates originated from soil organic nitrogen
      and NH4+ from fertilizer and rain. Nitrates in the middle and lower reaches were
      derived from the mixing of manure and sewage, soil organic nitrogen, and NH4+
      from fertilizer and rain. Jiangjia Spring, the outlet of the underground river,
      was seriously polluted by nitrates. It is believed that soil organic nitrogen,
      NH4+ in fertilizer and rain, the mixing of manure and sewage, and NO3- in
      precipitation were the main nitrate sources in the outlet. Nitrate source
      contribution of the outlet was calculated with the IsoSource model. The
      calculation results showed that manure and sewage, soil organic nitrogen, NH4+ in
      fertilizer and rain, and NO3- in precipitation contributed 46.4%, 32.6%, 18.6%,
      and 2.4%, respectively.

PMID- 30229603
TI  - [Spectral Characteristics of Dissolved Organic Matter in Landfill Groundwater].
AB  - Landfills have been the most common methods of organized waste disposal in China
      posing an incredible groundwater pollution threat. Dissolved organic matter (DOM)
      can be used to trace the source, species and migration of contaminants in
      groundwater, and the investigations of its composition, structure, and
      distribution play a role in environmental protection. This study investigated the
      DOM source, composition, and molecular structure in groundwater at landfills for
      different years of operation, and explored the dynamics of groundwater DOM
      evolution over time, usingmodern spectroscopy in combination with multivariate
      statistical analysis. The results showed that DOM in landfill groundwater was
      initially dominated by outputs from microbial activities, and this was followed
      by autogenous terrigenous input. In the early stages of landfilling, the DOM of
      microbial origin was significant; however, towards the late stages of
      landfilling, the presence of microbial DOM has weakened. The groundwater DOM with
      short landfill times were mainly composed of newly produced tryptophan and
      tyrosine, which had low humification, aromaticity, and molecular weight.
      Microbial activity was strong, and while there were initial, significant
      differences between sampling points, evidence of its presence could be used for
      early warning of contamination and monitoring should be conducted for its
      presence. Microbial activity weakened with longer landfill operation time,
      landfill waste tended towards stability, and the DOM in groundwater with high
      humification, aromaticity and molecular weight, was able to reduce the landfill
      impact on groundwater.

PMID- 30229604
TI  - [Adsorption Behavior of Phosphate from Water on Zirconium-loaded Granular Zeolite
      amended Sediment].
AB  - In this study, a zirconium-loaded granular zeolite (ZrGZ) was prepared,
      characterized and used as a sediment amendment to control internal phosphorus (P)
      loading in water samples from a heavily polluted river. The adsorption
      characteristics of phosphate on ZrGZ-amended sediment were investigated using
      batch experiments, and the stability of P in phosphate-adsorbed ZrGZ was
      evaluated using a sequential chemical extraction method. Results showed that the
      Langmuir isotherm model was more suitable for describing the equilibrium
      adsorption data of phosphate on ZrGZ-amended sediment than the Freundlich and
      Dubinin-Radushkevich isotherm models. The adsorption process of phosphate on ZrGZ
      amended sediment could be well described by the pseudo-second-order and Elovich
      kinetic models, and both film and intra-particle diffusion controlled the
      adsorption rate during the gradual adsorption stage. The coexistence of SO42- and
      HCO3- inhibited the adsorption of phosphate on ZrGZ-amended sediment, while
      coexisting Na+, K+, Mg2+ and Ca2+ enhanced the phosphate adsorption, and this
      promoting effect decreased in the order of Ca2+ > Mg2+ > Na+/K+. The ZrGZ-amended
      sediment exhibited a higher phosphate adsorption capacity than the unamended
      sediment, and the maximum phosphate adsorption capacity derived from the Langmuir
      isotherm model was found to be 336 mg.kg-1, which was higher than that for the
      unamended sediment (215 mg.kg-1). Sequential tests showed that P in phosphate
      adsorbed ZrGZ mainly existed in the form of NaOH-rP and Res-P, which was
      relatively unreactive. These results indicated that ZrGZ addition enhanced the
      phosphate adsorption capacity of river sediment, and that ZrGZ was a promising
      amendment for controlling the release of P from river sediment.

PMID- 30229605
TI  - [Control of Coagulant Dosing for Humic Substances Based on Ultraviolet Spectrum
      Analysis].
AB  - Humic substance (HS) is a main component of dissolved organic matter in the
      aquatic environment and significantly affects water treatment processes. To
      investigate the applicability and principle of UV spectrum analysis for
      coagulation control, laboratory jar tests were conducted with synthetic waters
      that had varying concentrations of HS and kaolinite. Thus, the influence of water
      quality conditions on the optimal coagulant dose (OCD) was determined and further
      correlated to Specific Ultraviolet Absorbance (SUVA254) and the ultraviolet
      spectral slopes of the coagulated water. Subsequently, the relationship between
      the UV spectral slopes and organic fractionation was further identified by using
      size exclusion chromatography (SEC). The results showed that the coagulant
      demands of the synthetic waters were positively related to dissolved organic
      carbon (DOC). Consequently, a stoichiometric relationship (0.61 mg.mg-1
      calculated as Al/DOC) was found between the coagulant demand and initial DOC of
      the synthetic water. As the coagulant dose increased, SUVA254 decreased from 8.9
      L.(mg.m)-1 to a steady level of 2.0 L.(mg.m)-1 and the removal efficiency of DOC
      was positively correlated with SUVA254. Spectral slopes in different wavelength
      ranges had showed similar tendencies, with S275-295 having the best correlation
      with SUVA254 (R2=0.81). Furthermore, SEC results demonstrated that coagulation
      preferentially removed humic substances, leading to reduced humification. As a
      result, S275-295 had the highest correlation with the portion of UVA254
      contributed by humic substances in water. Therefore, online measurement of
      ultraviolet spectral slopes was an important aspect in the control of coagulant
      dosing.

PMID- 30229606
TI  - [Reduction of Wastewater Organic Micro-pollutants and Genotoxicity in a Hybrid
      Process Involving Anaerobic-anoxic-oxic and Ozonation Treatments].
AB  - In recent years, researchers have drawn greater attention to the occurrence,
      fate, and risk of organic micro-pollutants (OMPs) in the environment. Effluent
      from municipal wastewater treatment plants (WWTPs) are an important source for
      the release of OMPs into aquatic environment and should be monitored and
      controlled. The migration and transformation of 14 selected OMPs and their
      reduction of genotoxicity after treatment by a hybrid process of anaerobic-anoxic
      oxic (AAO) and ozonation were investigated. Results showed that the activated
      sludge process was poor in removing most OMPs, with removal rates of less than
      50%. However, ozonation improved OMPs removal, and the hybrid process could
      reduce most of the OMPs by more than 90%-with OMPs containing phenolic, aniline,
      and anisole groups in their aromatic structures showing particular vulnerability
      to attack by ozone. The results of genotoxicity analyses showed that the
      wastewater influent and secondary effluent exhibited genotoxicity to an extent,
      and ozonation reduced the genotoxicity of secondary effluent by 98%, thus largely
      reducing the environmental risk posed by OMPs in WWTP effluent.

PMID- 30229607
TI  - [Distribution and Removal of Antibiotic Resistance Genes in Two Sequential
      Wastewater Treatment Plants].
AB  - Wastewater treatment plants (WWTPs) have been regarded as important point-sources
      of antibiotic resistance genes (ARGs) in aquatic environments. To investigate the
      distribution and removal of ARGs in WWTPs, a pharmaceutical wastewater treatment
      plant (PWWTP) and an integrated wastewater treatment plant (IWWTP) in a fine
      chemical industrial park were chosen, and polymerase chain reaction (PCR) and
      real-time PCR techniques were used to determine the occurrence and abundances of
      ARGs along the treatment processes. Ten and fifteen ARGs were detected initially
      in the influents of PWWTP and IWWTP respectively, in which tetracycline and
      sulfonamide resistance genes were frequently reported, while dfrA13 was first
      reported in WWTPs. The most abundant ARGs in the influents were sul I and sul II,
      followed by dfrA13, tetQ, floR, tetO, and tetW. The total ARGs increased by 0.21
      log after the treatment by PWWTP, whose effluent contributed 0.87% to the inflow
      yet 5.05% to the total ARGs of IWWTP. Finally the total ARGs removed by IWWTP was
      1.03 log, with the remaining ARGs then transported within the final effluent to
      the nearby coastal area. The authors concluded that the environmental and other
      impacts from the spread of ARGs on the microbial communities of the coastal
      environment needed further study.

PMID- 30229608
TI  - [Effect of Magnetic Chitosan Hydrogel Beads with Immobilized Feammox Bacteria on
      the Removal of Ammonium from Wastewater].
AB  - The bacterial reaction of ammonium oxidation coupling with iron reduction
      (Feammox) has been discovered recently. To improve the ammonium removal
      efficiency from wastewater of Feammox bacteria, magnetic chitosan hydrogel beads
      (MCHBs) were prepared via sodium hydroxide co-precipitating-sol-gel method,
      Feammox bacteria were immobilized to 1-5 mm MCHBs, and the ammonium removal
      efficiency by MCHBs-Feammox bacteria was compared to free-Feammox bacteria. In
      addition, the influences of initial ammonium concentration, pH and temperature
      were assessed. The results showed that the MCHBs were ferromagnetic and exhibited
      high crystallinity, with the magnetization of saturation of 29.46 emu.g-1. The
      average rates of ammonia oxidation and iron reduction increased by 42.96% and
      20.75% after Feammox bacteria immobilization, respectively, and the most
      significant effect was observed on 1-2 mm MCHBs-Feammox bacteria (P<0.05).
      Furthermore, 1-2 mm MCHBs immobilized bacteria worked in less favorable matrix
      concentrations, temperatures, and pH. Particularly, it could maintain high
      ammonium removal efficiency with 60.00 mg.L-1 initial ammonium concentration, 25C
      temperature and 4.50 pH. In addition, nitrate and ferrous ions were detected in
      the system. The highest ammonium removal rate occurred on day 16, reaching
      53.62%. These results indicated that MCHBs immobilization can improve the
      ammonium removal efficiency of Feammox.

PMID- 30229609
TI  - [Enhanced Nitrogen and Carbon Removal Performance of Simultaneous ANAMMOX and
      Denitrification (SAD) with Trehalose Addition Treating Saline Wastewater].
AB  - Enhanced nitrogen and carbon removal performance of simultaneous ANAMMOX and
      denitrification (SAD) process with trehalose addition treating saline wastewater
      was investigated in a sequencing batch reactor (SBR). The optimal nitrogen
      removal was achieved at 0.25 mmol.L-1 trehalose, during which NH4+-N, NO2--N, NO3
      -N, and COD could be completely removed. Compared to no addition of trehalose,
      ammonium removal efficiency (ARE), nitrite removal efficiency (NRE) and total
      nitrogen removal efficiency (TNRE) increased by 50%, 43% and 46%. Ammonium
      removal rate (ARR) and nitrite removal rate (NRR) increased by 81.25% and 75%,
      respectively. With increasing concentration of trehalose to 0.5 mmol.L-1, ARE was
      only 58.82% and the effluent concentration of NH4+-N was 33.25 mg.L-1. Compared
      to the Haldane model and the Aiba model, the Luong model was the most suitable to
      simulate the nitrogen removal performance of SAD with trehalose addition treating
      saline wastewater. The NRRmax, KS, Sm, and n fitted from Luong model were 0.954
      kg.(m3.d)-1, 0 mg.L-1, 184.785 mg.L-1, and 0.718, respectively. Compared to the
      modified Logistic model and the modified Boltzman model, the modified Gompertz
      model was the most suitable to describe the degradation of a substrate in a
      single cycle.

PMID- 30229610
TI  - [Characteristics of Denitrifying Phosphorus Removal by A2/O-BAF at Low
      Temperatures].
AB  - Low C/N domestic sewage was treated by an A2/O-biological aerated filter (BAF)
      system at low temperatures (11-14C). The characteristics of pollutant removal,
      the ratio of denitrifying phosphorus to nitrogen (DeltaPO43-/DeltaNO3-N) and
      effects of aeration flow and effective packing height on nitrification in BAF
      were studied. The results showed that when the average influent concentrations of
      COD, NH4+-N, TN and PO43- were 193.1, 58.6, 60.3 and 5.1 mg.L-1 respectively,
      their effluent concentrations were 46.3, 2.5, 13.4 and 0.3 mg.L-1 respectively,
      which met the first level A criteria specified in the discharge standard of
      pollutants for municipal wastewater treatment plant (GB 18918-2002). The linear
      fitting of DeltaPO43-/DeltaNO3--N was between 0.47 and 1.75. The normal
      distribution of mathematical statistics was applied-and the average standard
      deviation for DeltaPO43-/DeltaNO3--N were 1.20 and 0.29 respectively. When the
      aeration flows were 60 L.h-1 and 100 L.h-1, the effluent concentration of NH4+-N
      was less than 5.0 mg.L-1, corresponding to the effective packing heights in the
      BAF of 1.8 m and 1.0 m respectively. However, when the aeration flow was
      increased to 120 L.h-1, the air-water flow led to biofilm detachment, which
      caused the effluent concentration of NH4+-N to increase beyond 5.0 mg.L-1.

PMID- 30229611
TI  - [Characteristics of Advanced Treatment of Treated Petrochemical Water by O3-BAC
      and Analysis of Consortium Structure].
AB  - The advanced treatment of treated petrochemical water by Ozone-Biological
      Activated Carbon (O3-BAC) was carried out in this study. The effect of O3 on the
      removal of Chemical Oxygen Demand (COD) and Spectral Absorption Coefficient
      (UV254) were investigated. The characteristics of organic matter and the
      microbial consortium structure of BAC were also investigated at 20 mg.L-1 of O3
      dosage concentration, 40 min of O3 single stage contact time and 1.5 h of the
      empty bed residence time of BAC. Results showed that the effluent COD
      concentration of O3-BAC was 24 mg.L-1 with the removal efficiency of 40.4%. The
      COD removal efficiency of O3-BAC was higher than that for the BAC process. The
      UV254 removal efficiency of O3-BAC was 55.1%. Meanwhile, UV254 correlated with
      COD with a correlation coefficient of 0.89. The percentage of dissolved organic
      matters with relative molecular weight less than 1*103 increased from 69.0% to
      87.0% after O3 oxidation. The NPOC removal efficiency of O3-BAC (45.8%) was
      higher than that of the BAC process (23.0%). The NPOC removal efficiency of the
      BAC unit was mainly achieved by reduction of dissolved organic matters with
      relative molecular weight less than 1*103. GC-MS analysis results showed that
      organic substances such as alkanes, unsaturated esters, and phenols had been
      removed by O3 oxidation. The micro ecological environment of the BAC unit had
      been significantly improved after O3 oxidation, and the genera with relative
      abundance over 1.0% increased from 6 to 11. The combined O3-BAC system can be
      applied to the advanced treatment of petrochemical treated water.

PMID- 30229612
TI  - [Microbial Community Characteristics of Shortcut Nitrification Start-up in
      Different MBR-Inoculated Sludges].
AB  - In order to clarify the microbial community characteristics of the shortcut
      nitrification start-up with different inoculated sludges in the membrane
      bioreactor (MBR), the MBR was inoculated with nitrification sludge (R1),
      anaerobic nitrification sludge (R2) and 1:1 mixed inoculated anaerobic
      nitrification and denitrification sludge (R3). The results showed that the
      combination of intermittent aeration and shortened hydraulic retention time (HRT)
      successfully achieved the shortcut nitrification by R1, R2 and R3 reactors after
      46 d, 8 d and 30 d respectively, with the R2 reactor exhibiting the shortest
      start-up period. During stable operations, the average nitrite accumulation rates
      of R1, R2 and R3 reactors were 92%, 93% and 94% respectively, and the R3 reactor
      showed a more stable shortcut nitrification. The results of analyses using ACE,
      Chao, Shannon, and Simpson diversity indices showed that the microbial abundance
      and diversity levels of R1 and R2 were significantly lower than that of the
      inoculant during the stable operation period, while the species abundance in the
      R3 reactor was slightly reduced and the diversity level was slightly changed. The
      main bacteria in the three reactors were Proteobacteria and Bacteroidetes after
      the successful start-up of shortcut nitrification, and the relative abundance of
      Proteobacteria was increased compared with the inoculated sludge. Proteobacteria
      were the main denitrifying bacteria, with beta-Proteobacteria being the dominant
      bacteria of the shortcut nitrification system in the three reactors, accounting
      for 59.6%, 63.6% and 69.3% respectively. Through further analysis, the next
      dominant bacteria in R1, R2 and R3 were all Nitrosomonas, with 12.8%, 20.2% and
      19.7% respectively. Compared with the R1 reactor, there was a certain proportion
      of shortcut nitrification bacteria in the sludge of the R2 and R3 reactors, which
      was more favorable to the operation of the shortcut nitrification system.

PMID- 30229613
TI  - [Effect of Microbial Community Structure and Metabolites on Sludge Settling
      Ability Under Three Different Switching Condition Processes].
AB  - Using sodium acetate as the carbon source, sludge settling ability
      (settleability) was investigated under three processes:AAO nitrogen and
      phosphorus removal(process I), AO nitrification-denitrification (process II), and
      aerobic carbon removal (process III). The succession of microbial community
      structures in sludge was traced, the content and composition of microbial
      metabolites were monitored, and the effects of operational mode on sludge
      settleability were analyzed. The results showed that the settleability of process
      I was the best, followed by process III and II. Under the different operating
      conditions, the dominant bacteria and microbial community structure of the system
      changed significantly. The relative amount of Thiothrix was the dominant bacteria
      affecting the sludge settleability. The abundances of Thiothrix were only 0.08%
      and 1.51% with fresh sludge and in process I; this abundance increased to 9.41%
      in process II and decreased to 4.29% in process III. The anaerobic zone of
      process I had an inhibitory effect on the growth of the bacterium, while the
      anoxic zone of process II stimulated its dominant growth. At the same time,
      comparison showed that the microbial population diversity was highest in process
      I. followed by processes II and III. The introduction of anoxic and anaerobic
      zones led to the increase of system function and environmental complexity, and
      increased microbial community diversity. Analyses of extracellular polymeric
      substances (EPS) and fluorescence characteristics showed that the changes in
      microbial community structure had a significant effect on the composition and
      content of EPS, which aggravated the process of improving or deteriorating
      settleability. The sludge settleability was found to be positively correlated
      with the ratio of protein and polysaccharide in loosely bound EPS.

PMID- 30229614
TI  - [Adsorption Mechanisms of Ciprofloxacin by Extracellular Polymeric Substances of
      Sulfate-reducing Bacteria Sludge].
AB  - Extracellular polymeric substances (EPS) in microbial sludge, fulfils a key role
      in removal of micro-organic pollutants during biological wastewater treatment. In
      this study, the authors evaluated the removal of ciprofloxacin (CIP) by sulfate
      reducing bacteria (SRB) sludge in a sulfate-reducing up-flow sludge bed (SRUSB)
      reactor, and examined the role of EPS on CIP removal in an SRB sludge system. The
      results indicated that CIP was removed efficiently through adsorption and
      biodegradation by SRB sludge, with adsorption the major removal pathway. EPS also
      played an important role in CIP adsorption by SRB sludge, and the adsorption
      mechanisms of CIP by EPS were investigated using the three-dimensional excitation
      emission matrix fluorescence spectroscopy technologies combined with parallel
      factor analysis. The functional groups binding CIP onto EPS were identified
      through Fourier transform infrared (FTIR) spectra analysis. The results suggested
      that the static quenching of EPS following CIP adsorption led to formation of an
      EPS-CIP complex, and that the CIP was mainly bound with tryptophan and tyrosine
      like protein substances in EPS with the binding constants of 1.43*104 L.mol-1 and
      1.02*104 L.mol-1, respectively. The FTIR results suggested that hydroxyl, amino
      and carboxyl functional groups were mainly responsible for binding of CIP onto
      EPS. The results revealed the adsorption mechanisms of CIP by EPS in SRB sludge,
      and enhanced understanding of the role of EPS in sulfur-mediated biological
      processes for the removal of CIP and other organic micro-pollutants.

PMID- 30229615
TI  - [Rapid Improvement of Denitrification Performance of Embedded Activated Sludge
      and Community Analysis].
AB  - The purpose of this study was to rapidly improve the denitrification packing
      activity in the denitrification pond sludge of sewage plants, to realize the
      engineering application of embedding immobilization, and to explore the
      characteristics of the microbial community of the embedding packing. The effects
      of different C/N ratios, temperature, and pH on the activity of embedding filler
      were studied by batch experiments, and the biological community characteristics
      of embedding filler were studied by high-throughput sequencing. Results showed
      that the embedding packing in C/N to 10, the temperature of 30C, and pH of 7.5+/
      0.3, resumed 5.37 mg.(g.h)-1 of the initial activity after 7 days. Under the
      optimized culture conditions of C/N ratio of 10, temperature of 25C, and pH of
      8.0, the specific rate of denitrification can be increased by 15 times to 80.17
      mg.(g.h)-1 after 15 days, and stabilized at that level. SEM results showed that
      there were a large number of mass transfer channels inside the embedding fillers,
      and that the bacteria grew well as clusters in the encapsulated fillers. The high
      throughput sequencing showed that the denitrifying function of Thauera and
      Thermomonas were 24.27% and 8.23% respectively, which ensured the high efficiency
      of denitrifying nitrogen removal. The rapid proliferation of Thauera dominant
      bacteria and Thermomonas under optimal culture conditions was the main reason for
      the rapid increase of packing activity.

PMID- 30229617
TI  - [Spatial Interpolation Methods and Pollution Assessment of Heavy Metals of Soil
      in Typical Areas].
AB  - It is important to choose the best spatial interpolation method to reflect
      spatial distribution features and evaluate soil heavy metal pollution. The
      spatial distribution of arsenic (As) and cadmium (Cd) concentrations in top soil
      samples from Hubei Province were studied by four frequently-used spatial
      interpolation methods, including inverse distance weighted (IDW), radial basis
      function (RBF), local polynomial interpolation (LPI) and ordinary kriging (OK).
      The interpolation precision and effect of the spatial distribution of the four
      methods were compared with the results of cross validation and spatial
      distribution, and the pollution was assessed by the geoaccumulative index (Igeo)
      and indicator kriging (IK). The results showed that the four interpolation
      methods had small prediction errors, but that the interpolation effects were
      quite different. Among them, LPI had the most serious smoothing effect, followed
      by OK. The IDW and RBF best retained the extreme value information for element
      concentrations, and interpolation results were more detailed-and so to accurately
      understand the distribution of soil heavy metals, IDW or RBF methods were
      recommended. Taking the arithmetic mean of heavy metal concentrations in deep
      soil of Hubei Province as the background value, the evaluation result of geo
      cumulative index pollution allowed exceedance percentages for As and Cd accounted
      for 5.5% and 99.0% respectively. The soils of the study areas were heavily
      contaminated with Cd. The pollution evaluation result from IK showed that high
      probability contaminated areas, with moderate-heavy contamination levels, were
      mainly located in the central part of the study area. The authors concluded that
      development of agriculture in the research area should include attention to Cd
      pollution and that soils there required the effective treatment and restoration
      of Cd levels.

PMID- 30229616
TI  - [Spatial-Temporal Trends and Pollution Source Analysis for Heavy Metal
      Contamination of Cultivated Soils in Five Major Grain Producing Regions of
      China].
AB  - Heavy metal pollution of farmland soils in China has been identified as a threat
      to ecosystem safety and human health. A total of 3006 soil samples were analyzed
      from arable lands in five grain producing regions of China, which included data
      from published studies from 2000 up to now. An additional 656 historical samples
      were derived from the 1980s by a digitizing grained point sites map (Cd, Pb, As,
      Ni, Cu, Zn, Cr, and Hg) from the PRC Atlas of Soil Environmental Background
      Values. A GIS-based approach and single factor index method were employed to
      identify the current status and spatial distribution of heavy metal (Cd, Pb, As,
      Ni, Cu, Zn, Cr, and Hg) contamination in agricultural soils, and these were then
      compared with historical data to explore contamination trends over time. Then,
      based on the Igeo method and the effects of the surrounding environment on
      contamination rates, pollution sources were analyzed. Results showed that 21.49%
      of the agricultural soil samples exceeded the environmental quality standard set
      by the Ministry of Environmental Protection. The proportions of slight, moderate,
      and severe pollution were 13.97%, 2.50%, and 5.02%, respectively. Pollution is
      more extensive in the south compared with the north. Exceedance percentages in
      the Sichuan Basin (SC), Yangtze River Middle Plain and Jianghuai Plain (CJ),
      Huang-Huai-Hai Plain (HHH), Songnen Plain (SN), and Sanjiang Plain (SJ), were
      43.55%, 30.64%, 12.22%, 9.35%, and 1.67%, respectively. The main pollutants were
      Cd, Ni, Cu, Zn, and Hg, with exceedance percentages of 17.39%, 8.41%, 4.04%,
      2.84%, and 2.56%, respectively. Since the 1980s, heavy metal pollution has
      increased by 14.91%. The proportion of Cd, Ni, Cu, Zn, and Hg increased by
      16.07%, 4.56%, 3.68%, 2.24%, and 1.96%, respectively. Except for SJ, exceedance
      percentages in cultivated land increased significantly, while the exceedance
      percentages of Cd, Ni, and Cu in the southern areas were higher than for the
      northern areas-although the growth rate of Hg and Cr in the south was lower than
      that in the north. The main sources of Cd and Hg were anthropogenic pollution,
      while the other six heavy metals were from predominantly natural sources.
      However, about 20.00% of Pb, Zn, and Cu were affected by anthropogenic
      activities. Mining, industry, and sewage water were the main sources of
      pollution. In addition to the larger impact of sewage irrigation in the north,
      other sources of pollution showed greater influence in the south. Mining mainly
      caused pollution by Cd, Hg, Ni, Cr, and Cu, while excessive levels of Cd, Ni, Cu,
      Zn, and Hg was the signature of industrial pollution. Irrigation with sewage
      effluent causes excessive Cd, Ni, and Zn. Results from this study provide
      valuable information for agricultural soil management and food safety in China.

PMID- 30229618
TI  - [Effect of Straw Residues in Combination with Reduced Fertilization Rate on
      Greenhouse Gas Emissions from a Vegetable Field].
AB  - Greenhouse gases mainly come from farmland soils. Re-spreading chaff (straw
      returning) is an effective ecological management in China. Quantitative analysis
      of straw residues together with reduced fertilization rates can provide a
      scientific basis for reducing greenhouse gas emissions. A field experiment with
      six different fertilizer amounts combined with straw residues was carried out in
      a vegetable field (lettuce-cabbage-chili rotation), including the control (CK),
      conventional fertilizing (F), straw returning with 100% conventional fertilizing
      (100FS), straw returning with 70% conventional fertilizing (70FS), straw
      returning with 60% conventional fertilizing (60FS),and straw returning with 50%
      conventional fertilizing (50FS). The dynamic characteristics and emission factors
      of CO2, CH4 and N2O in the soil were analyzed using an in-situ, closed chamber,
      gas chromatography-based system, from November 2016 to September 2017. The
      results showed that the emission of CO2, CH4 and N2O has seasonal variation
      characteristics. The peak value mainly occurred in April to August, and the gas
      emission peak would appear after fertilizing and irrigating. Compared with F
      treatment, straw returning with fertilizing treatments reduced the N2O emission
      fluxes, cumulative emission and emission factor, especially in the 100FS
      treatment. The N2O cumulative emission and emission factor was 60.76 kg.hm-2,
      0.138 kg.kg-1 (N2O-N/N) respectively in 100FS treatment during planting chili was
      more than that during planting lettuce and cabbage. Moreover, straw returning
      with reducing conventional fertilizing could reduce the N2O emission factor
      compared with 100FS treatment. The CO2 emission fluxes 55.28-1831.62[mg.(m2.h)-1]
      and cumulative emission (7502.13-25988.55 kg.hm-2) in 70FS treatment were lower
      than that in CK and F treatments, while other treatments increased the CO2
      emission fluxes and cumulative emission, especially in 60FS and 50FS treatments.
      During planting lettuce and cabbage, the CH4 cumulative emission mainly showed
      negative values in treatments except for CK, indicating that soil could adsorb
      CH4. Moreover, straw returning with 30%-50% conventional fertilizing treatment
      could reduce CH4 emission fluxes and cumulative emission during planting chili,
      but increased in 100FS. Compared with CK and F treatment, generally, straw
      retuning with conventional fertilizing could significantly increase the global
      warming potential (GWP) in the study, except for 70FS treatment. 70FS could
      reduce the CO2, CH4 emission and the GWP of greenhouse gases, but could not
      significantly affect N2O emission reduction.

PMID- 30229619
TI  - [Emission of NH3 and N2O from Spinach Field Treated with Different Fertilizers].
AB  - Agricultural management techniques such as fertilizer or manure application have
      substantial influence on NH3 and N2O emissions and, by understanding this
      influence, management strategies can be developed to reduce them. An experiment
      was conducted in a greenhouse at Hunan Agricultural University during 2012 to
      2013, to investigate effects of different fertilizers on NH3 and N2O emissions.
      The treatments included control without fertilizer (CK), swine composting
      fertilizer (SC), stored swine manure fertilizer (SS), and chemical fertilizer
      (FC). The fluxes of NH3 and N2O were collected by venting method and static
      chamber method, respectively. The results showed that during the spinach growth
      season, compared with FC, loss of both NH3 and N2O for SC were reduced by 52.9%
      and 95.12%, respectively(P<0.01). However, loss of NH3 for SS increased by 24.8%,
      and loss of N2O reduced by 48.8% compared with FC. Loss rate of NH3 were SS
      (10.97%) > FC (4.19%) > SC(2.74%), and emission coefficient for N2O were
      FC(4.50%) > SC(2.21%) > SS(0.60%). Yield and utilization of nitrogen for SC were
      reduced by 19.61% and 13.20% compared with FC, respectively, but not
      significantly; and significantly reduced by 27.9% and 40.0% compared with SS,
      respectively. Loss of gases (NH3 and N2O) for SC were 1.83%, which was the
      lowest, while utilization of nitrogen for SC was 13.20%, similar with FC.
      Greenhouse temperature was not the critical factor during the spinach planting in
      winter, but soil water was. Therefore, optimizing manure management could reduce
      ammonia volatilization and N2O emission loss without decreasing vegetables
      production, and the present data indicated that SC would be optimal for better
      yields with reduced ammonia volatilization and N2O emission loss.

PMID- 30229620
TI  - [Effects of Various Combinations of Fertilizer, Soil Moisture, and Temperature on
      Nitrogen Mineralization and Soluble Organic Nitrogen in Agricultural Soil].
AB  - An 84-day laboratory incubation experiment was conducted to investigate the
      effects of different fertilizers (urea; manure), moisture conditions (60%, 75%
      and 90% water holding capacity) and temperatures (15, 25 and 35C) on nitrogen
      mineralization. The experiment included 3 treatments:1CK, unfertilized control; 2
      Ur, adding urea at N 120 mg.kg-1; 3 UM, adding urea and manure (equal to adding N
      120 mg.kg-1). Total inorganic nitrogen and soluble organic nitrogen (SON) were
      determined at different times throughout the experiment. The results showed that
      soil temperature and fertilization type had significant impacts on the net
      mineralization rates, cumulative mineralization, and the potentially
      mineralizable nitrogen (N0) (P<0.01). In addition, the soil net N mineralization
      rates and cumulative mineralization significantly (P<0.05) increased by 1.46-8.17
      and 2.00-8.15 times, respectively, when fertilizers were added into soils. The
      soil net N mineralization rates and cumulative mineralization increased with the
      increase of temperature. Compared with CK treatment, Ur and UM treatments could
      significantly increase the content of soil soluble organic nitrogen(SON). There
      was a significant negative correlation between the content of SON and cumulative
      mineralization. It indicated that SON was involved in soil nitrogen
      mineralization as a non-negligible component. Increasing the temperature could
      significantly increase the mineralization rate and mineralization intensity of
      SON in soil, but the water content had no significant influence on the SON of the
      soils. Moreover, the authors found that fertilization treatment worked
      significantly in decreasing the Q10 value for soil N mineralization compared with
      CK treatment. Further, the Q10 value was significantly lowest in UM
      treatment(Q10=1.01). The results showed that the application of organic manure
      significantly reduced the sensitivity of the rate of nitrogen mineralization to
      temperature changes, which was beneficial in slowing down the release rate of
      mineral nitrogen under high temperatures and improving the nitrogen utilization
      efficiency of crops.

PMID- 30229621
TI  - [Long-term Fertilization Effects on the Abundance of Complete Ammonia Oxidizing
      Bacteria(Comammox Nitrospira) in a Neutral Paddy Soil].
AB  - The discovery of the complete ammonia-oxidizing microbes, Comammox Nitrospira,
      had fundamentally changed our perspective on traditional nitrification. The
      microbe also played a potentially under-appreciated role in the biogeochemical N
      cycle and provided a new dimension for the research of nitrification. To
      investigate the abundance of Comammox in different ecosystems was urgently
      needed. In the present study, three treatments with different quantities of
      fertilization in a paddy soil (blank control, NPK and 1.5 NPKS) to investigate
      the nitrification and amoA gene abundance for nitrifying microorganisms,
      especially for the complete ammonia oxidizing bacteria (Comammox Nitrospira). The
      results showed that:1 Both Comammox Clade A and Comammox Clade B were detected in
      all three treatments, and the abundance of Comammox Clade A were 9.0*107,
      1.7*108, 7.2*108 copies.g-1 (dry soil), respectively, and for Comammox Clade B
      were 1.5*107, 1.2*107, 1.7*107 copies.g-1 (dry soil), respectively. 2 The
      abundances of both ammonia-oxidizing archaea (AOA)in the three fertilizers was
      1.5*107-1.2*108 copies.g-1 (dry soil), and the ammonia-oxidizing bacteria (AOB)
      in the three fertilizers was 2.0*105-9.3*107 copies.g-1 (dry soil), lower than
      the abundance of the Comammox. The ratio of Comammox to AOA was 7.2, and the
      ratio for Comammox to AOB was 524.4 for blank control, were greater than NPK and
      1.5 NPKS treatments. 3 The ratio of Comammox Clade A to Comammox Clade B showed
      an increasing trend with the increase in fertilizer application, at 6.1, 14.4 and
      43.1, respectively. 4 For NPK and 1.5 NPKS treatments, Comammox Clade A amoA gene
      copies were 1.9 and 8.0 times higher than that of the blank control treatment
      respectively, and the numbers for AOA significantly increased to 3.2 and 7.2
      times that of the blank control. The AOB gene copy numbers increased by two
      orders of magnitude compared with the blank control. In addition, the
      nitrification potential increased with the increase in N fertilizer application;
      however, the effects of different fertilizer treatments on Comammox Clade B were
      not significant. Results indicated that Comammox was widely distributed in the
      neutral purple paddy soil and was higher in abundance than AOA or AOB, which
      implied that Comammox-especially Clade A-may contribute to the nitrification of
      paddy soil.

PMID- 30229622
TI  - [Spatial Variation of Soil Organic Carbon and Stable Isotopes in Different Soil
      Types of a Typical Oasis].
AB  - Soil organic carbon (SOC) and its stable isotope composition reflect important
      information on ecosystem carbon cycle. Under the background of global change, it
      is of great significance to study carbon dynamics and sustainable development of
      carbon resources in terrestrial ecosystems. In this study, four soil types in
      Alar oasis were studied to determine SOC content and delta13 C value at different
      layers, and the differences of delta13CSOC abundance and its relationship with
      soil environmental factors were also discussed. Three main outcomes were drawn
      from the results. 1The total organic carbon (TOC) content of the soil was in the
      order of irrigated desert soil > brown desert soil > saline soil > aeolian sandy
      soil, and had a higher value in the surface layer (0-20 cm layer); delta13CSOC
      ranged from -260/00--230/00, the surface layer (0-20 cm) was in the order saline
      soil > aeolian sandy soil > irrigated desert soil > brown desert soi. 2 Both SOC
      and delta13CSOC were significantly affected by soil type and their interaction,
      and by soil depth. Furthermore, the effect test of interaction indicated that SOC
      was significantly impacted by environmental factors, but the impact on
      delta13CSOCwas relatively weak. 3 The results of redundancy analysis showed that
      SOC had a significant or extremely significant positive correlation with soil
      inorganic carbon, total nitrogen, soil water content and bulk density, and had a
      significant negative correlation with C/N. There was also a significant positive
      correlation between delta13CSOC and conductivity, and in addition, delta13CSOC
      was negatively correlated with soil inorganic carbon and soil water content. The
      analyses showed that SOC and its isotopes changed with soil types, and that the
      effect of soil type was stronger than that of soil depth, which was mainly
      determined by soil moisture content.

PMID- 30229623
TI  - [Effect and Mechanism of Attapulgite and Its Modified Materials on
      Bioavailability of Cadmium in Soil].
AB  - The effect of attapulgite (magnesium aluminium phyllosilicate) and its modified
      materials on the extractability of soil Cd and the accumulation of Cd in lettuce
      (Lactuca sativa) were investigated using a pot-culture experiment, and the
      immobilization mechanism of attapulgite and its modified materials was explored
      through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR)
      and X-ray photoelectron spectroscopy (XPS). The results showed that attapulgite
      and its modified materials could significantly reduce the Cd concentration in
      Lactuca sativa, with maximum reductions of 41.0% and 56.5%, respectively, and
      attapulgite modified materials treatments appeared more efficient than
      attapulgite treatments in reducing Cd uptake of Lactuca sativa. The saturated
      adsorption capacity for the adsorption of Cd2+ on attapulgite rose distinctly
      after being modified. Attapulgite and its modified materials could significantly
      reduce Cd content in soil CaCl2 extract at the dosage of 1%, with the maximum
      reduction rates of 34.2% and 34.3%, respectively. The attapulgite formed a
      complex to immobilize Cd mainly through the surface silanol and Cd2+ complexation
      reaction, while the modified attapulgite formed a complex mainly through the
      complexation of Cd2+ with carboxyl groups which existed in addition to the
      complexation with surface hydroxyl, thus reducing the mobility of Cd2+ and
      achieving remediation of Cd-contaminated soil. In summary, attapulgite and its
      modified materials can both be used for remediation of Cd-contaminated soil, and
      the mechanisms for this function were found to be different.

PMID- 30229624
TI  - [Persulfate Oxidation Effect of Soil Organic Pollutants by Natural Organic
      Matters].
AB  - This study explored the degradation effect and mechanism of persulfate oxidation
      activated by different macromolecular substances (polysaccharides, humic acid,
      and citric acid), combined with ferrous ions and different kinds of carbohydrate
      (monosaccharide, disaccharide, and polysaccharide). The results showed that the
      oxidation effects of total petroleum hydrocarbons (TPHs) and polycyclic aromatic
      hydrocarbons (PAHs) by different activation treatments were in the order:humic
      acid combined with ferrous ion > polysaccharide > citric acid chelated with iron
      > polysaccharide combined with ferrous ion > disaccharides > monosaccharide > CK.
      Among them, humic acid combined with ferrous ion-activated persulfate achieved
      the highest removal rates (up to 79.21% and 79.89%, respectively), and also
      showed the weakest pollutant content rebound phenomenon. For oxidation of high
      ring PAHs, humic acid combined with ferrous ion treatment and polysaccharide
      activation showed great advantages, with degradation rates being 77.96% and
      84.37%, much higher than other treatments. Humic acid combined with ferrous ion
      activated persulfate result in the highest Eh of soil (up to 618-676 mV), and
      polysaccharide treatment was secondary, indicating that macromolecular materials
      exhibited great oxidation ability and can degrade soil organic pollutants
      efficiently.

PMID- 30229625
TI  - [Lead Uptake and Accumulation in Rice (Oryza sativa L.) with Water Management and
      Selenite Fertilization].
AB  - Lead (Pb) accumulation in rice grains has been identified as a potential threat
      to human health. Our study investigated the effects of varied rates of selenite
      fertilization (0, 0.5 and 1.0 mg.kg-1) on the dynamics of Pb in soil solutions,
      and its uptake and translocation by rice under different water management
      scenarios (aerobic and flooded) in pot experiments. Plants were harvested at
      seedling stage and at maturity to determine the Pb contents, and soil solutions
      were extracted during the growing season to monitor the Pb dynamics. Results
      showed that flooding the soil significantly increased Pb concentrations in DCB
      extracts and rice roots both at seedling stage and maturity. Root Pb contents in
      flooded treatments were 4.2-8.5 and 1.4-1.5 times higher than those under aerobic
      conditions at rice seedling stage and maturity. Flooding also decreased the
      percentage of Pb in rice shoots. The Pb content in soil solutions, rice
      seedlings, rice roots and stems at maturity were significantly decreased by
      selenite additions. Relative to the control treatment, selenite additions
      decreased the rice root Pb contents by 5.4%-24.3% and 2.7%-61.7% under flooding
      and aerobic conditions at seedling stage, respectively; while decreased Pb in
      rice root by 56.1%-64.1% and 53.8%-63.2% respectively, at maturity. No
      significant differences existed in grain Pb levels among the treatments. Results
      demonstrated that water management regimes and selenite additions affected Pb
      uptake by rice roots significantly, but had no significant influence on Pb
      accumulation in rice grains.

PMID- 30229627
TI  - [Oxidation of Humic Acid Complexing As(III) by As(III)-Oxidizing Bacteria].
AB  - The interaction between soil arsenic and soil microorganisms has been identified
      as one of the important parts of the morphological transformation of soil
      arsenic. In order to investigate the interaction between Humic Acid complexing
      As(III)[HA-As(III)] and As(III)-oxidizing bacteria (HN-2), the changes in arsenic
      speciation in the liquid phase and the solid phase, with different pH, were
      studied. The results indicated there was better As(III) oxidation efficiency in
      the pH 7 reaction system. A part of As(III) would be discharged from the HA
      As(III) solid phase during hours 0-10 in the reaction system, with or without HN
      2, and meanwhile it was found that HN-2 oxidized As(III) to As(V) rapidly, while
      As(III) was oxidized into As(V) by HA gradually. As(III) complexing HA can be
      transformed into free-As(III), and then oxidized into free-As(V) by HN-2 over
      hours 10-24 of the reaction. The system achieved the equilibrium state after 48
      h. The results of the X-ray absorption near edge structure (XANES) further
      confirmed the conclusions above.

PMID- 30229626
TI  - [Key Bacteria for the Microbial Degradation of Pollutants in Cellar Water].
AB  - The study aimed to identify the key bacteria and the potential interactions among
      these bacteria during the degradation of pollutants in cellar water, The main
      pollution characteristics were nitrogen, phosphorus and organic pollution. The
      structure and function of the bacterial community and its correlation with water
      quality variables were analyzed. A network of seven associations of microbial co
      occurrence was set up, based on 16S rRNA and the model for inferring co
      occurrence or interspecific interactions of microbial species. This showed that
      there were a large number of microorganisms with relatively specific ecological
      functions in the cellar water, and that many metabolic activities were involved.
      The ecological relationships of most bacteria in the association network were a
      form of mutualism. The most prominent genera included Lacibacter, Arthrobacter,
      Candidatus Protochlamydia, Methylocaldum, Sulfuritalea, Mycobacterium,
      Aquirestis, Rhodobacter, and, Methylotenera. The strong associations were
      observed between following bacteria:Sulfuritalea-Rhodobacter, Azospirillum
      Rhodobacter, Methylocaldum-Rhodobacter, Arthrobacter-Rhodobacter, Rhodoplanes
      Rhodobacter, Candidatus Protochlamydia-Rhodobacter, Methylotenera-Rhodobacter,
      Rhodobacter-Aquirestis, Mycobacterium-Rhodobacter, Planctomyces-Candidatus
      Solibacter, Planctomyces-Legionella, Hymenobacter-Adhaeribacter, and
      Luteolibacter-Crenothrix. It was considered that Rhodobacter, Methylocaldum,
      Methylotenera, Acinetobacter, Novosphingobium, Planctomyces, Hymenobacter, and
      Luteolibacter were the key bacteria involved in microbial degradation of cellar
      water pollutants, and Rhodobacter was the representative genus of the key
      bacteria. The authors concluded that the research results improved understanding
      of the microbial degradation mechanism of pollutants in cellar water.

PMID- 30229628
TI  - [A Thermotolerant and Halotolerant Sulfate-reducing Bacterium in Produced Water
      from an Offshore High-temperature Oilfield in Bohai Bay, China: Isolation,
      Phenotypic Characterization, and Inhibition].
AB  - The growth and activity of sulfate-reducing prokaryotes (SRP) in oilfield
      environments could produce large amounts of H2S, leading to multifaceted
      problems, including oilfield souring and microbially-influenced corrosion, yet
      knowledge about the diversity and physiology of SRP therein was quite limited. To
      further understand the phenotypic characteristics of SRP residing in an offshore
      high-temperature oilfield at Bohai Bay, China, and to explore the potential
      methods for control of SRP-mediated problems, we isolated, using Hungate
      techniques, a thermotolerant, halotolerant SRP strain, designated BQ1, from the
      produced water of a high-temperature. We also presented the phenotypic features
      of BQ1, and investigated the efficacy of five biocides, or metabolic inhibitors,
      in suppressing the sulfidogenic activity of BQ1. Cells of BQ1 were motile, short
      rod-shaped, 1.2-2.5 MUm in length and 0.5-0.8 MUm in width. Although BQ1 shared
      99% 16S rRNA gene sequence similarity with Desulfovibrio vulgaris Hildenborough,
      distinct phenotypic traits between them were observed. Isolated BQ1 could grow at
      14-70C(optimum at 30C) and pH 6.0-9.0 (optimum pH 7.0), and in the presence of 0%
      10% NaCl. Isolated BQ1 utilized a wide range of carbon substrates, including
      sodium formate, sodium lactate, and acetate. Sulfate, sulfite, thiosulfate, and
      sulfur were utilized as electron acceptors, but not nitrate or nitrite. Sodium
      hypochlorite (600 mg.L-1), Benzyltrimethylammonium chloride (300 mg.L-1), or
      nitrate (800 mg.L-1) failed to inhibit H2S production by BQ1. By contrast,
      glutaraldehyde (50 mg.L-1), bronopol (30 mg.L-1), chlorine dioxide (50 mg.L-1),
      and nitrite (70 mg.L-1) inhibited H2S production by BQ1 for at least 30 d,
      indicating that these compounds may be suitable for the mitigation of microbial
      souring in this specific, high-temperature, offshore oilfield at Bohai Bay,
      China.

PMID- 30229629
TI  - [Isolation and Nitrogen Removal Characteristics of Salt-tolerant Heterotrophic
      Nitrification and Aerobic Denitrification Bacteria Zobellella sp. B307].
AB  - A heterotrophic nitrification and aerobic denitrification strain, B307, was
      isolated from the sediment of Jiaozhou Bay. The strain was identified by 16S rRNA
      sequence analysis, and its optimization condition and salt-tolerance
      characteristics were studied by single factor experiment. The denitrification
      effect in single or mixed nitrogen sources was investigated under optimum
      conditions. The results allowed the strain to be identified as Zobellella sp.,
      based on 16S rRNA sequence analysis. The best carbon source was sodium succinate,
      and the optimum C/N was 5, the optimal initial pH was 9, and the optimal
      temperature was 35-40C respectively. After 12 hours, the NH4+-N and the NO3--N
      removal efficiencies were 98.35% and 99.75% in a mixed nitrogen source system.
      The removal efficiencies for NH4+-N and NO3--N were 97.67% and 94.39% within 24
      hours when salinity was 75 g.L-1. The strain has highly efficient heterotrophic
      nitrification-aerobic denitrification ability and strong salt tolerance, which
      demonstrated that the strain has potential for extensive application for nitrogen
      removal in high salt wastewater.

PMID- 30229631
TI  - [Effect of Fluoroquinolones on Performance and Microbial Community of a Vertical
      Flow Constructed Wetland].
AB  - In order to investigate the effect of multiple fluoroquinolones on the
      performance and microbial community of a constructed wetland, ofloxacin,
      norfloxacin, and ciprofloxacin were added to the influent of the vertical flow
      constructed wetland for two months. Results indicated that COD removal rate
      gradually decreased after adding antibiotics, with the minimum removal rate of
      70.94%, followed by gradual recovery. TP removal rate also decreased, with some
      fluctuations, while ammonia removal remained stable. Fluoroquinolones thus have
      an important effect on COD and TP removal from the constructed wetland, but there
      is no evident effect on ammonia removal. Based on results of the Shannon index
      and Shannoneven index, there were no significant changes in the microbial
      community, while the Chao1 index increasing significantly. Comparing community
      composition before and after antibiotic addition, the relative abundance of
      Proteobacteria decreased from 44.90% to 34.12%, still maintaining its
      predominance, while Firmicutes increased from 2.55% to 10.55%. At the class
      level, beta-Proteobacteria declined from 17.03% to 8.36%, while the relative
      abundance of Clostridia, Bacilli, and Bacteroidia increased from 0.50%, 1.85%,
      and 0.10% to 4.21%, 4.64%, and 2.56%, respectively. The genera Dechloromonas and
      Pseudarthrobacter decreased from 8.56% and 5.10% to 3.16% and 1.53%,
      respectively, while Trichococcus, Tessaracoccus, and Desulfovibrio increased from
      0.66%, 0.03%, and 0.02% to 3.84%, 3.83%, and 2.06%, respectively. The microbial
      community of the constructed wetland thus changed under the pressure of multiple
      fluoroquinolones.

PMID- 30229630
TI  - [Isolation, Identification and Degradation Characteristics of a 17beta-estradiol
      Degrading Strain Fusarium sp. KY123915].
AB  - A 17beta-estradiol (E2) degrading strain (designated as Wu-SP1) was isolated from
      the activated sludge collected from a wastewater treatment plant (WWTP) in Xi'an.
      The strain was identified as Fusarium sp. according to 18S rDNA sequence and
      phylogenetic analysis. The optimal pH and temperature for E2 degradation were 6
      and 30C, respectively. Under these conditions, the E2 biodegradation rate of 2
      mg.L-1 E2 amounted to 92.5% within 48 h by this strain. The kinetics of E2
      degradation by the strain KY123915 were in good accord with the first-order
      equation, with the concentration ranged from 10 to 500 mg.L-1. UV spectrum
      analysis showed the strength of maximum absorption of metabolites became weak
      compared to E2, indicating that E2 may be degraded via estrone (E1) by Fusarium
      sp. KY123915.

PMID- 30229632
TI  - [Microbial Community Diversity Analysis During Composting of Lincomycin Mycelia
      Dreg with Manure].
AB  - Aerobic composting experiments were conducted using lincomycin mycelia wastes
      (dreg) and manure (T), using sewage sludge with manure as a control (CK). High
      performance liquid phase methods and high throughput sequencing were used to
      determine the concentration of lincomycin residue and to characterize the
      microbial community. The results showed that lincomycin was reduced
      significantly, with the concentration decreasing from 1800 mg.kg-1 to 483 mg.kg
      1, accounting for 73% degradation. In addition, the bacterial community abundance
      and diversity indices were all lower than that of sludge-manure at the mesophilic
      and thermophilic phases, because of the high concentration of lincomycin residue
      in lincomycin mycelia dreg. By contrast, the fungal community abundance and
      diversity indices showed the reverse, due to the high content of organic matter
      and nitrogen in lincomycin mycelia dreg. Therefore, the microbial communities
      were greatly different between T and CK treatment with the domain genera of
      Paucisalibacillus, Cerasibacillus, Bacillus, Virgibacillus, Ureibacillus,
      Paenibacillus, and Sinibacillus in T compost and Truepera, Actinomadura,
      Pseudosphingobacterium, Pseudomonas, Luteimonas and Ureibacillus in CK compost.
      However, as the composting continued to a mature phase, most of the lincomycin
      was reduced, and the differences between the two microbial communities gradually
      decreased. This showed that composting could make lincomycin mycelia dreg
      harmless and could be used to turn it into a resource.

PMID- 30229633
TI  - [Oxidative Stress and DNA Damage Induced by DEP Exposure in Earthworms].
AB  - Diethyl phthalate (DEP) is a plastic additive that entered the soil environment
      due to the extensive use of plastic products. However, its toxicity to soil
      animals and the associated toxicity mechanism were not completely understood.
      Eisenia foetida was selected as the research object and exposed to simulated
      contaminated soil with different concentrations of DEP. Antioxidant enzyme
      activity, reactive oxygen species (ROS) content, Glutathione-S-Transferase (GST)
      activity, Malondialdehyde (MDA) content and amount of DNA damage in the
      earthworms were used as evaluation parameters for the study. The results showed
      that under DEP stress, the activities of antioxidant enzymes, GST and ROS in
      earthworms changed and resulted in gene damage. Under the stress of 0.1-50 mg.kg
      1 DEP exposure during the 28 d experiment, the level of ROS increased and there
      was a "dose-effect" relationship. Excessive ROS gave rise to an increase of MDA
      content in the body from lipid peroxidation. Under the combined action of ROS and
      MDA, DNA in the body cavity of earthworm was damaged and there was also a "dose
      effect" relationship between the degree of damage and the concentration of DEP.
      In summary, DEP may cause a certain degree of damage to organisms, with damage to
      the DNA of earthworms representing fairly strong eco-toxicological effects.
      Therefore, adequate attention should be paid to DEP disposal.

PMID- 30229634
TI  - [Mineralogy Characteristics and Heavy Metal Distribution of MSWI Fly Ash].
AB  - Fly ash from municipal solid waste incineration (MSWI) plants can be categorized
      as a highly toxic mineral material due to the potential for leaching heavy
      metals. The mineralogical properties of MSWI fly ash visually reflect the heavy
      metals distribution in the ash, and are closely related to the release and
      migration behaviors of heavy metals in fly ash disposal or utilization scenarios.
      In order to understand the distribution of heavy metals in MSWI fly ash and
      provide support for heavy metals control technology, comprehensive tests on the
      macroscopic and microscopic mineralogical characteristics of the fly ash were
      conducted using X-ray diffraction (XRD), scanning electron microscope, a mineral
      liberation analysis system, and other methods. The results showed that MSWI fly
      ash was a heterogeneous material of closely combined mineral and non-mineral
      phases. The main mineral phases identified by XRD included chlorides and calcium
      bearing minerals, mainly calcite and portlandite. The element distribution
      analysis, conducted with a mineral liberation analyzer, revealed that heavy
      metals of MSWI fly ash were mainly present in three forms:uniform distribution in
      the non-mineral amorphous phase, isomorphism in calcite and other minerals, and
      adsorption on the surfaces of quartz and hematite. Most content of Cu and Cr were
      distributed in the non-mineral phase due to their lower volatility, while most of
      semi-volatile heavy metals (43.92% of Zn and 60.61% of Cd) were present in
      mineral phases. In particular, Cd, Cr and Zn were mainly present in calcite,
      hematite and silicates respectively.

PMID- 30229635
TI  - Kaposi's Sarcoma lung metastastis in transplanted patient treatment response with
      Paclitaxel and Everolimus.

PMID- 30229636
TI  - Analysis of neoplastic skin complications in transplant patients: experience of
      an italian multidisciplinary transplant unit.
AB  - BACKGROUND: Transplant patients need to be strictly followed, since the
      immunosuppressive therapies they usually receive can increase the risk of skin
      complications. This study aims to evaluate the prevalence of neoplastic skin
      complications in transplant patients. METHODS: We analyzed 256 liver or kidney
      transplant patients. The follow-up mean period was 7+/-3,5 years. It was also
      evaluated the prevalence of cutaneous neoplastic complications according to the
      immunosuppressive regimen received by patients as follows: cyclosporine,
      tacrolimus, steroids, mycophenolate mofetil or everolimus, in single, double or
      triple therapy. RESULTS: The 18.36% of patients developed neoplastic
      complications, among these 9,37% actinic keratoses , 8.20% non melanoma skin
      cancer, and 0.78% cutaneous melanoma. Among patients who developed non melanoma
      skin cancer, 61.90% had basal cell carcinoma, 23.81% squamous cell carcinoma, 52%
      Kaposi's sarcoma and 4.76%, Malherbe's epithelioma. CONCLUSIONS: This study
      demonstrated the increased risk of skin cancer in transplant patients during the
      first 7 years of follow-up and made the dermatologists aware about the need of a
      regular cutaneous follow up for this subset of patients.

PMID- 30229637
TI  - Isotretinoin-triggered acne fulminans: a rare, disabling occurrence.

PMID- 30229638
TI  - Clinical and trichoscopic correlation of primary neutrophilic scarring alopecia:
      folliculitis decalvans and dissecting cellulitis.

PMID- 30229639
TI  - Non-familial porphyria cutanea tarda: a case report of a rare disease.

PMID- 30229640
TI  - Skin involvement in patients with psoriatic arthritis: preliminary results of
      treatment with apremilast in real world setting.
AB  - BACKGROUND: Apremilast is a "small molecule", an oral phosphodiesterase 4
      inhibitor indicated for the twice- daily treatment of adults with psoriasis (PsO)
      and psoriatic arthritis (PsA). Data concerning clinical experience in real world
      setting with Apremilast for psoriasis are still exiguous, and aim of this report
      is to provide our experience in the use of Apremilast in out-patient setting.
      METHODS: Ten caucasian individuals (6 male, 4 females; mean age 69,3; range 53-81
      years) affected by moderate to severe plaque psoriasis (PASI>=10 e/o DLQI>=10 e/O
      BSA>=10) were treated with Apremilast, following dosing regimen of technical data
      sheet and clinically evaluated both after 12 weeks (T12) and 16 weeks (T16). At
      baseline median PASI was 14 (range 10 - 25, SD 5.0). The median BSA was 17,55 (10
      - 25, SD 6.0), the median PGA was 3.5 (2 - 5, SD 1.1), the median DLQI was 7,3 (5
      - 18, SD 3.6). The median absolute value of PASI, BSA, PGA and DLQI showed a
      statistically significant decrease (p<0.05) already after 12 weeks of treatment.
      RESULTS: At T12, 6 patients out from 10 (60%) reached PASI 50 and 3/10 patients
      (30%) reached PASI 75. At T16, 9 patients out from 10 patients (9/10, 90%)
      reached PASI75, and 3/10 (30%) reached PASI90. Five patients out from 10 (50%)
      reached MDA at T16. Diarrhoea was the main side effect occurring during the first
      weeks of treatment, that resolved spontaneously over the time. CONCLUSIONS:
      Although our preliminary results need to be confirmed by further larger
      observational studies, seem to confirm the efficacy and safety profile provided
      through the ESTEEM registrative trials (ESTEEM 1-2).

PMID- 30229641
TI  - Anetodermic lesions following pityriasis rosea and impetigo.

PMID- 30229642
TI  - Late-onset post-mammoplasty pyoderma gangrenosum treated with tobacco-pouch
      suture combined with oral corticosteroids.

PMID- 30229643
TI  - Role of high-resolution ultrasound in the evaluation of psoriatic onychopathy.

PMID- 30229644
TI  - [Risk factors and clinical evolution of carbapenemase-producing Klebsiella
      pneumoniae infections in a university hospital in Spain. Case-control study].
AB  - OBJECTIVE: Carbapenemase-producing Enterobacterias is a global health hazard due
      to their ease of transmission, difficulty of treatment, and their personal and
      economic impact. We analyze the factors associated with an increased risk of
      infection by Klebsiella pneumoniae carbapenemase-producing bacteria (KPC) and
      factors related to poor prognosis. METHODS: We designed a case-control study. KPC
      isolates were taken during an outbreak in a hospital in Madrid. A logistic
      regression was performed with the main variables. RESULTS: Sixteen cases of
      clinically documented infections were isolated. Overall mortality rates in the
      cases group was 25%. The most frequent location was blood (37.5%) followed by
      urine (25%). All but one were OXA-48. Regarding factors related to an increased
      risk of developing infection, only previous exposure to antibiotics presented
      statistical significance difference OR 13 (2.40-70.46). With respect to the
      overall mortality, the presence of pneumonia OR 25 (1.93-323.55) or the use of
      invasive mechanical ventilation was associated with greater risk 15 OR 33 (1.92
      122.8) For attributable mortality only invasive ventilation had a significant
      association OR 18 (1.48-218.95). CONCLUSIONS: Exposure to previous antibiotics is
      an independent risk factor for developing KPC infection, adjusted for all other
      clinical and demographic variables. Risk factors such as the presence of
      pneumonia or the use of invasive mechanical ventilation were associated with a
      worse prognosis in terms of overall and attributable mortality.

PMID- 30229645
TI  - Comparison of culture, microscopic smear and molecular methods in diagnosis of
      tuberculosis.
AB  - OBJECTIVE: Tuberculosis (TB) is a public health problem worldwide, with the
      highest mortality . The development of nucleic acid-based tests for detection of
      Mycobacterium tuberculosis complex (MTBC) has significantly increased sensitivity
      compared to conventional smear microscopy and provides results within a matter of
      hours compared to weeks for solid culture, which is the current gold standart.
      The aim of this study was to compare the culture, microscopic smear and molecular
      method in the diagnosis of TB. METHODS: Seven hundred ninety specimens belonging
      to clinically suspected cases of TB were studied retrospectively. The specimens
      were grouped as respiratory and non-respiratory and the groups were compared for
      mycobacterial detection assays. The culture and the molecular diagnostic
      GeneXpert MTB/RIF (GX) assay method were compared. RESULTS: When culture was used
      as the reference standart, 32 (4.05%) specimens were positive for MTBC. Of the 32
      culture positive clinical specimens 24 (3.03%) were respiratory and 8 (1.01%)
      were non-respiratory specimens. All 24 of the 24 respiratory specimens were
      positive by the GX test, Seven of the eight non-respiratory specimens positive
      for culture were positive by GX assay. Five of the seven hundred fifty-eight
      samples of culture negative were positive with GX assay. Sensitivity and
      specificity of GX were found to be 96.8 % and 99.3 %, respectively. CONCLUSIONS:
      Molecular methods to acquire time in diagnosis as well as the increase in
      linearity gives a different perspective to the diagnosis of tuberculosis. The GX
      assay has a diagnostic utility for rapid diagnosis of TB.

PMID- 30229646
TI  - Excellent Efficacy of MOF Films for Bronze Artwork Conservation: The Key Role of
      HKUST-1 Film Nanocontainers in Selectively Positioning and Protecting Inhibitors.
AB  - Development of metal-organic framework (MOF) films for selectively positioning
      inhibitors in metallic anticorrosion applications remains a substantial challenge
      due to the difficulty of controlling the arrangement of inhibitor molecules in
      MOF pores. Cetyltrimethyl ammonium bromide (CTAB), which contains hydrophobic and
      hydrophilic tails, was chosen as a prototypical inhibitor and was selectively
      located in the pores of the classic HKUST-1 thin film on a metallic surface.
      Experimental results reveal that the prepared CTAB@HKUST-1 film displays good
      metallic anticorrosion performances, especially for bronze conservation. A
      possible anticorrosion mechanism of CTAB@HKUST-1 is proposed and fully discussed.
      The study provides an avenue for developing MOF-based thin films for metallic
      anticorrosion applications to address the environmental development issues
      related to corrosion.

PMID- 30229647
TI  - Friction-Active Surfaces Based on Free-Standing Anchored Cellulose Nanofibrils.
AB  - A specific feature of fibrous surfaces is the dependence of their mechanical
      properties on the alignment of the fibers. Vertically aligned fibers enhance
      friction and adhesion, whereas horizontal fibers are known to act as a lubricant
      reducing the friction. Many plants form a specific fibrous mucilage cover around
      their seeds upon hydration. This mucilage consists of cellulose, hemicelluloses,
      and strongly hydrophilic pectins. We show that the controlled critical-point
      drying of hydrated seed mucilage of three exemplary seed mucilage-rich plant
      species results in the exposure of free-standing cellulose nanofibers with a very
      high aspect ratio and anchored to the seed surface. The structural dimensions of
      the cellulose nanofibers are similar to the vertically aligned carbon nanotubes
      and the contact elements in the adhesion system of the gecko that show an
      outstanding high dry friction and adhesion. Tribological experiments demonstrate
      very high average friction coefficients when sliding a smooth and stiff probe
      over the surface of such arrays of dry free-standing cellulose nanofibrils in the
      range from 1.4 to 1.8. The high friction values most likely arise from bending of
      the single cellulose fibers and their alignment with the counterpart surface in
      close contact. We suggest the potential of free-standing cellulose nanofibrils of
      plant seed mucilage as a natural and ecologically friendly material where high
      contact forces to surfaces in dry environments are desired.

PMID- 30229648
TI  - Theory of the Double Layer in Water-in-Salt Electrolytes.
AB  - One challenge in developing the next generation of lithium-ion batteries is the
      replacement of organic electrolytes, which are flammable and most often contain
      toxic and thermally unstable lithium salts, with safer, environmentally friendly
      alternatives. Recently developed water-in-salt electrolytes (WiSEs), which are
      nonflammable, nontoxic, and also have enhanced electrochemical stability, are
      promising alternatives. In this work, we develop a simple modified Poisson-Fermi
      theory for WiSEs, which demonstrates the fine interplay between electrosorption,
      solvation, and ion correlations. The phenomenological parameters are extracted
      from molecular dynamics simulations, also performed here. The theory reproduces
      the WiSEs' electrical double-layer structure with remarkable accuracy.

PMID- 30229650
TI  - Fluorinated Vitrimer Elastomers with a Dual Temperature Response.
AB  - Vitrimers are an emerging new class of permanently cross-linked polymeric
      materials that show a liquid behavior upon heating wherein the macroscopic
      deformation is controlled by the rate of internal chemical bond exchange
      reactions. Thus, quite uniquely among polymeric materials, flow rates and
      material viscosities can be enhanced or controlled by the addition of catalysts
      and additives. We now report a catalyst-free vitrimer system, prepared from
      mixing two simple components, wherein two competing bond exchange mechanisms
      coexist, each showing a strikingly different temperature dependence, related to
      the large difference in activation energy for the different exchange pathways (60
      vs 130-170 kJ/mol). The low barrier process is predominant at lower temperatures,
      but is outcompeted by the high barrier process that becomes dominant at higher
      temperatures because of its much more pronounced temperature dependence. The
      result is an interesting and highly unusual dual viscosity profile for this new
      class of vitrimer materials: a very gradual decrease in viscosity at lower
      temperatures, intercepted by a much sharper drop in viscosity at higher
      temperatures. The highly counterintuitive effect where a higher barrier pathway
      is dominant over a much lower barrier process can be rationalized by the exchange
      mechanisms that involve different reactive species, but lead to the overall same
      exchange. We observed this unusual but highly promising behavior first for
      fluorinated vitrimer elastomers, aimed at high performance materials, but the
      effect was also shown to hold in related nonfluorinated elastomers. A new way to
      control and design the rheological behavior of vitrimers toward finely tuned and
      precisely controlled processing applications has thus been provided.

PMID- 30229651
TI  - Proteomic Response to Thaxtomin Phytotoxin Elicitor Cellobiose and to Deletion of
      Cellulose Utilization Regulator CebR in Streptomyces scabies.
AB  - Streptomyces scabies is responsible for common scab disease on root and tuber
      vegetables. Production of its main phytotoxin thaxtomin A is triggered upon
      transport of cellulose byproducts cellotriose and cellobiose, which disable the
      repression of the thaxtomin biosynthesis activator gene txtR by the cellulose
      utilization regulator CebR. To assess the intracellular response under conditions
      where S. scabies develops a virulent behavior, we performed a comparative
      proteomic analysis of wild-type S. scabies 87-22 and its cebR null mutant (hyper
      virulent phenotype) grown in the absence or presence of cellobiose. Our study
      revealed significant changes in abundance of proteins belonging to metabolic
      pathways known or predicted to be involved in pathogenicity of S. scabies. Among
      these, we identified proteins of the cello-oligosaccharide-mediated induction of
      thaxtomin production, the starch utilization system required for utilization of
      the carbohydrate stored in S. scabies's hosts, and siderophore synthesis
      utilization systems, which are key features of pathogens to acquire iron once
      they colonized the host. Thus, proteomic analysis supported by targeted mass
      spectrometry-based metabolite quantitative analysis revealed the central role of
      CebR as a regulator of virulence of S. scabies.

PMID- 30229652
TI  - Synthesis and Mechanochemical Activation of Ladderene-Norbornene Block
      Copolymers.
AB  - We have recently reported a polymechanophore system, polyladderene (PLDE), which
      dramatically transforms into polyacetylene (PA) upon mechanical stimulation.
      Herein, we optimized conditions to synthesize unprecedented block copolymers
      (BCPs) containing a force-responsive block by sequential ring-opening metathesis
      polymerization of different norbornenes and bromoladderene. Successful extension
      from PLDE to other blocks required careful timing and low temperatures to
      preserve the reactivity of the PLDE-appended catalyst. The PLDE-containing BCPs
      were sonochemically activated into visually soluble PA with a maximum absorption
      lambda >= 600 nm and unique absorption patterns corresponding to noncontinuous
      activation of ladderene units. Access to polymechanophore BCPs paves the way for
      new stress-responsive materials with solution and solid state self-assembly
      behaviors and incorporation of polymechanophores into other materials.

PMID- 30229649
TI  - 1H NMR Metabolomics Identifies Underlying Inflammatory Pathology in
      Osteoarthritis and Rheumatoid Arthritis Synovial Joints.
AB  - Despite osteoarthritis (OA) and rheumatoid arthritis (RA) being typically age
      related, their underlying etiologies are markedly different. We used 1H nuclear
      magnetic resonance (NMR) spectroscopy to identify differences in metabolite
      profiles in low volumes of OA and RA synovial fluid (SF). SF was aspirated from
      knee joints of 10 OA and 14 RA patients. 100 MUL SF was analyzed using a 700 MHz
      Avance IIIHD Bruker NMR spectrometer with a TCI cryoprobe. Spectra were analyzed
      by Chenomx, Bruker TopSpin and AMIX software. Statistical analysis was undertaken
      using Metaboanalyst. 50 metabolites were annotated, including amino acids,
      saccharides, nucleotides and soluble lipids. Discriminant analysis identified
      group separation between OA and RA cohorts, with 32 metabolites significantly
      different between OA and RA SF (false discovery rate (FDR) < 0.05). Metabolites
      of glycolysis and the tricarboxylic acid cycle were lower in RA compared to OA;
      these results concur with higher levels of inflammation, synovial proliferation
      and hypoxia found in RA compared to OA. Elevated taurine in OA may indicate
      increased subchondral bone sclerosis. We demonstrate that quantifiable
      differences in metabolite abundance can be measured in low volumes of SF by 1H
      NMR spectroscopy, which may be clinically useful to aid diagnosis and improve
      understanding of disease pathogenesis.

PMID- 30229653
TI  - Total Mercury and Methylmercury in Lake Water of Canada's Oil Sands Region.
AB  - Increased delivery of mercury to ecosystems is a common consequence of
      industrialization, including in the Athabasca Oil Sands Region (AOSR) of Canada.
      Atmospheric mercury deposition has been studied previously in the AOSR; however,
      less is known about the impact of regional industry on toxic methylmercury (MeHg)
      concentrations in lake ecosystems. We measured total mercury (THg) and MeHg
      concentrations for five years from 50 lakes throughout the AOSR. Mean lake water
      concentrations of THg (0.4-5.3 ng L-1) and MeHg (0.01-0.34 ng L-1) were similar
      to those of other boreal lakes and <5% of all samples exceeded Provincial water
      quality guidelines. Lakes with the highest THg concentrations were found >100 km
      northwest of oil sands mines and received runoff from geological formations high
      in metals concentrations. MeHg concentrations were highest in those lakes, and in
      smaller productive lakes closer to oil sands mines. Simulated annual average
      direct deposition of THg to sampled lakes using an atmospheric chemical transport
      model showed <2% of all mercury deposited to sampled lakes was emitted from oil
      sands activities. Consequently, spatial patterns of mercury in AOSR lakes were
      likely most influenced by watershed and lake conditions, though mercury
      concentrations in these lakes may be perturbed with future development and
      climatic change.

PMID- 30229654
TI  - Novel Vapor-Phase Synthesis of Flexible, Homogeneous Organic-Inorganic Hybrid
      Gate Dielectric with sub 5 nm Equivalent Oxide Thickness.
AB  - Organic-inorganic hybrid dielectrics have attracted considerable attention for
      improving both the dielectric constant ( k) and mechanical flexibility of the
      gate dielectric layer for emerging flexible and wearable electronics. However,
      conventional solution-based hybrid materials, such as nanocomposite and self
      assembled nanodielectrics, have limitations in the dielectric quality when the
      thickness is deep-scaled, which is critical to realizing high-performance
      flexible devices. This study proposes a novel vapor-phase synthesis method to
      form an ultrathin, homogeneous, high- k organic-inorganic hybrid dielectric. A
      series of hybrid dielectrics is synthesized via initiated chemical vapor
      deposition (iCVD) in a one-step manner, where 2-hydroxyethyl methacrylate and
      trimethylaluminum are used as the monomer and inorganic precursor, respectively.
      The thickness and composition are effectively controlled to form a uniform,
      defect-free hybrid dielectric. As a result, the synthesized hybrid dielectric has
      a high- k value as high as 7 and exhibits a low leakage current density of less
      than 3 * 10-7 A/cm2 at 2 MV/cm, even with an equivalent oxide thickness of less
      than 5 nm. Furthermore, the dielectric layer shows exceptional chemical stability
      without any degradation in its dielectric performance and a smooth surface
      morphology. The dielectric layer also has good flexibility, maintaining its
      excellent dielectric performance under a tensile strain of up to 2.6%. Organic
      thin-film transistors with the developed hybrid dielectric as the gate dielectric
      achieved hysteresis-free transfer characteristics, with an operating voltage of
      up to 4 V and excellent mechanical flexibility as well. The hybrid dielectric
      synthesized via the iCVD process is a promising candidate for high-performance,
      low-power flexible electronics.

PMID- 30229655
TI  - Highly Sensitive and Discriminative Detection of BTEX in the Vapor Phase: A Film
      Based Fluorescent Approach.
AB  - BTEX (benzene, toluene, ethylbenzene, o-xylene, m-xylene, and p-xylene)
      represents a group of volatile organic compounds (VOCs) and constitutes a great
      threat to human health. However, sensitive, selective, and speedy detection of
      them on-site and in the vapor phase remains a challenge for years. Herein, we
      report a film-based fluorescent approach and a conceptual sensor, which shows
      unprecedented sensitivity, speed, and reversibility to the aromatic hydrocarbons
      in the vapor phase. In the studies, pentiptycene was employed to produce a
      nonplanar perylene bisimide (PBI) derivative, P-PBI. The compound was further
      utilized to fabricate the film. The novelty of the design is the combination of
      capillary condensation and solvent effect, which is expected to enrich the
      analytes from vapor phase and shows outputs at the same time. Importantly, the
      film permits instant response (~3 s) and real-time identification (<1 min) of
      benzene and toluene from other aromatic hydrocarbons. The experimental detection
      limits (DLs) of the six analytes are lower than 9.2, 2.7, 1.9, 0.2, 0.4, and 0.4
      ppm, which with the exception of benzene, are significantly lower than the NIOSH
      recommended long-term exposure limits. More importantly, the film is
      photochemically stable, and more than 300 repetitive tests showed no observable
      bleaching. In addition, the sensing is fully reversible. The superior performance
      of the film device is in support of the assumption that the combination of
      capillary condensation and solvation effect would constitute an effective way to
      design high-performance fluorescent films, especially for challenging chemical
      inert and photoelectronically inactive VOCs.

PMID- 30229656
TI  - Dynamics and Microstructures of Nicotine/Water Binary Mixtures near the Lower
      Critical Solution Temperature.
AB  - The orientational dynamics and microscopic structures of nicotine/water binary
      mixtures near the system's lower critical solution temperature (LCST) were
      elucidated using optical heterodyne-detected optical Kerr effect (OHD-OKE)
      spectroscopy, nuclear magnetic resonance correlation spectroscopy (NMR COSY),
      first-principles calculations, and molecular dynamics simulations. Water
      concentrations were investigated from zero to close to pure water. At
      temperatures below the LCST, OHD-OKE experiments measured an anomalous slowing as
      the phase transition concentration was approached. At moderate concentrations and
      low temperatures, intermolecular cross-peaks between nicotine and water molecules
      were observed in the COSY spectra, demonstrating the formation of structures that
      persist for milliseconds. These results suggest that pair correlations contribute
      to the slowdown in the OHD-OKE data at moderate water concentrations. First
      principles calculations revealed that intermolecular hydrogen bonding
      coordination between nitrogen atoms in pyridine moieties and water lowers the
      energy barriers for the reorientations of the two nicotine rings. Atomistic
      simulations demonstrate that with increasing water concentration, hydrogen
      bonding interactions between pyridine moieties and water molecules first increase
      and then decrease with a maximum at moderate water concentrations. These
      experimental and computational characterizations of the dynamics of nicotine
      molecules are attributed to the distinct configurations of water molecules around
      the pyridine ring moieties in nicotine molecules.

PMID- 30229657
TI  - Gold Nanoparticle Couples with Entropy-Driven Toehold-Mediated DNA Strand
      Displacement Reaction on Magnetic Beads: Toward Ultrasensitive Energy-Transfer
      Based Photoelectrochemical Detection of miRNA-141 in Real Blood Sample.
AB  - Highly stable circulating microRNAs (miRNAs) are currently recognized as a novel
      potential biomarker for clinical cancer diagnosis in the early stage. However,
      limited by its low concentration, high sequence similarity, as well as the
      numerous interferences in body fluids, detection of miRNA in whole blood with
      sufficient selectivity and sensitivity is still challenging. Herein, we reported
      the integration of entropy-driven toehold-mediated DNA strand displacement (ETSD)
      reaction with magnetic beads (MB) toward the energy-transfer-based
      photoelectrochemical (PEC) detection of the prostate carcinoma (PCa) biomarker
      miRNA-141 in a real blood sample. In this protocol, the ETSD reaction was divided
      into two steps, and cooperated with magnetic separation, target extraction and
      amplification could be realized in a single test and ultrasensitive detection of
      miRNA-141 could be achieved in undiluted whole blood sample. This work proposed a
      new solution for sensitive biomolecular detection in a complex biological milieu
      and exhibited great promise for future clinical cancer diagnosis.

PMID- 30229658
TI  - [4 + 2] Annulation of 3-Nitroindoles with Alkylidene Malononitriles: Entry to
      Substituted Carbazol-4-amine Derivatives.
AB  - A general and transition-metal-free method for the construction of the carbazol-4
      amine motif via a vinylogous Michael
      addition/cyclization/isomerization/elimination reaction of 3-nitroindoles with
      alkylidene malononitriles has been developed. This novel methodology allows the
      facile synthesis of a series of di- and trisubstituted carbazol-4-amine
      derivatives in moderate to good yields. A gram-scale experiment was successfully
      performed, highlighting the practicability of this method. Moreover, this
      strategy is also applicable to 3-nitrobenzothiophene, affording the corresponding
      dibenzo[ b, d]thiophen-1-amine derivatives in moderate yields.

PMID- 30229659
TI  - Switchable Single-Walled Carbon Nanotube-Polymer Composites for CO2 Sensing.
AB  - We report a chemiresistive CO2 sensor based on single-walled carbon nanotubes
      (SWCNTs) noncovalently functionalized with a CO2 switchable copolymer containing
      amidine pendant groups that transform into amidinium bicarbonates in response to
      CO2. To fabricate a robust surface-anchored polymer-SWCNT dispersion via spray
      coating, we first designed and synthesized a precursor copolymer, P(4VP-VBAz),
      bearing both 4-vinylpyridine (4VP) groups and azide groups. The SWCNT dispersant
      group, 4VP, is capable of debundling and stabilizing nanotubes to improve their
      solubility in organic solvents for solution processing. Well-dispersed P(4VP
      VBAz)-SWCNT composites are covalently immobilized onto a glass substrate
      functionalized with alkyl bromides, and then the amidine moieties are
      subsequently attached to form the resulting CO2-switchable P(Q4VP-VBAm)-SWCNT
      composites via a copper(I)-catalyzed azide-alkyne cycloaddition click reaction at
      the film surface. The amidine groups are strong donors that compensate or pin
      carriers in the SWCNTs. In the presence of CO2 under humid conditions, the
      generated amidinium bicarbonates from the polymer wrapping increase the
      concentration and/or liberate the hole carriers in the nanotubes, thereby
      increasing the net conductance of the composites. The amidinium moieties revert
      back to the amidines when purged with a CO2-free carrier gas with a reversible
      decrease in conductance. We also demonstrate high selectivity to CO2 over the
      other atmospheric gases such as O2 and Ar.

PMID- 30229660
TI  - Charge Injection and Electrical Response in Low-Temperature SnO2-Based Efficient
      Perovskite Solar Cells.
AB  - Defining low-temperature engineering protocols for efficient planar perovskite
      solar cell (PSC) preparation is important for fabrication simplification and low
      cost production. In the present work, we have defined a low-temperature (123 
      degrees C) protocol for the preparation from a solution of SnO2 layers which are
      efficient for an application as an electron transporting layer (ETL) in PSCs.
      Thin, conformal, and transparent layers have been obtained. The related PSCs have
      shown best devices with a power conversion efficiency of 18.22% and low
      hysteresis J- V curves (a hysteresis index of 6.7%). Charge injection has been
      thoroughly studied by photoluminescence decay measurements. The decay curves
      followed a biexponential function. The injection of holes into the spiro-OMeTAD
      layer was found very fast and is a no-limiting step. On the other side, the
      charge injection into the oxide ETLs depends on its structure and on the oxide.
      The time constant for the low-temperature SnO2 layers is close to that of the
      mesoporous benchmark layers with a fast (surface) and a slow (bulk) component at
      11 and 129 ns with relative contributions calculated at 13% and 87%,
      respectively. The phenomena occurring at a longer time scale have been
      investigated by impedance spectroscopy. The SnO2 cell spectra showed no
      intermediate-frequency inductive loop. The very low frequency part of the spectra
      was characterized by the beginning of an arc of a circle at the origin of a very
      large resistance over a large applied potential range. This resistance, along
      with an intermediate-frequency resistance, has been assigned to a recombination
      resistance and explains the very large  Voc achievable with SnO2 PSCs. The
      existence of a capacitance at the intermediate frequency with a noticeable low
      value at about 0.2 mF.cm-2 is linked with the low hysteresis of the devices.

PMID- 30229661
TI  - Integrase Strand Transfer Inhibitor Resistance Mutations in Antiretroviral
      Therapy-Naive and Treatment-Experienced HIV Patients in South Korea.
AB  - Updated guidelines for the treatment of antiretroviral therapy (ART)-negative
      patients with HIV recommend integrase strand transfer inhibitor (INSTI)-based
      regimens. HIV patients are tested for resistance to antiretrovirals, and the
      reported prevalence of transmitted INSTI resistance remains rare worldwide.
      However, no data related to INSTI resistance in Korean HIV patients have been
      reported. We aimed to determine the prevalence of INSTI resistance-related
      mutations in South Korea. We subjected both ART-naive (n = 58) and ART
      experienced Korean HIV patients (n = 41) to genotypic resistance analysis and
      determined a prevalence of INSTI major resistance mutations of 3.4% (n = 2) among
      ART-naive patients and 22.0% (n = 9) among ART-experienced patients. In the
      former group, both major INSTI resistance cases involved the nonpolymorphic E92Q
      mutation in the integrase strand. Our findings suggest that INSTI resistance
      testing should be included in the standard resistance screening protocols for
      Korean HIV patients.

PMID- 30229662
TI  - Comparative study of the efficacy of selective laser trabeculoplasty as initial
      or adjunctive treatment for primary open-angle glaucoma.
AB  - AIM: The aim of this study is to compare the efficacy of selective laser
      trabeculoplasty as initial or adjunctive treatment for primary open-angle
      glaucoma in a retrospective chart review. METHODS: 28 eyes of 28 patients with
      newly diagnosed primary open-angle glaucoma, who formed the initial selective
      laser trabeculoplasty group, and 31 eyes of 31 patients suffering from medical
      uncontrolled primary open-angle glaucoma, who formed the adjunctive selective
      laser trabeculoplasty group, were treated with 180 degrees  selective laser
      trabeculoplasty. Patients were evaluated 1, 3, 6, 12, 18 and 24 months after
      treatment. Success was defined as an intraocular pressure lowering exceeding 20%
      of pretreatment intraocular pressure. RESULTS: The mean follow-up time was 20.25
      months (standard deviation = 8.1) for the initial selective laser trabeculoplasty
      group and 18.87 months (standard deviation = 8.8) for the adjunctive selective
      laser trabeculoplasty group (p = 0.538). No significant difference was found
      between the two groups for mean pretreatment intraocular pressure (21.43 mmHg
      (standard deviation = 3.2) vs 21.97 mmHg (standard deviation = 2.6); p = 0.766),
      for mean intraocular pressures and mean intraocular pressure reductions during
      whole follow-up period. At all follow-up visits, the mean percent intraocular
      pressure reduction was smaller in the adjunctive selective laser trabeculoplasty
      group than in the initial selective laser trabeculoplasty group, and such a
      difference was significant at 1 month (21.55% vs 26.79%; p = 0.039) and 24 months
      (24.82% vs 28.10%; p = 0.041). According to the Kaplan-Meier survival analysis,
      the 24-month success rate was 71.4% in the initial selective laser
      trabeculoplasty group and 71% in the adjunctive selective laser trabeculoplasty
      group, with no differences between the groups (p = 0.913). CONCLUSION: Selective
      laser trabeculoplasty is equally efficient in reducing intraocular pressure as
      initial or adjunctive treatment for primary open-angle glaucoma over 24 months.

PMID- 30229663
TI  - TAX-mRNA-Carrying Exosomes from Human T Cell Lymphotropic Virus Type 1-Infected
      Cells Can Induce Interferon-Gamma Production In Vitro.
AB  - Human T cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV
      1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell
      leukemia/lymphoma. The development of HAM/TSP, a chronic neuroinflammatory
      disease, is correlated to complex interaction between the host immune response
      and the infecting virus. Tax expression plays an important role in HAM/TSP
      pathogenesis by activating various cellular genes, including the cytokines
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha).
      Exosomes have emerged as an important factor of cell-to-cell communication
      contributing to diverse cellular processes, including immune modulation.
      Considering the potential role of exosomes in modulating the immune response and
      inflammation, the main objective of this study was to examine if HTLV-1-infected
      cells produce exosomes carrying viral proteins or inflammatory molecules, which
      can participate in the chronic inflammation that is observed in patients with
      HAM/TSP. Exosomes were isolated from HTLV-1-infected cell line, evaluated for the
      tax mRNA presence, and tested for the ability to activate peripheral mononuclear
      cells (PBMC) in inducing an inflammatory immune response. We observed that the
      proinflammatory cytokines, IFN-gamma and TNF-alpha, were upregulated in T cells
      after treatment of the PBMC with Tax-carrying exosomes compared to the negative
      control. Interleukin-4, Granzyme B, and Perforin did not show alterations. Taken
      together, these results suggest that exosomes carrying tax-mRNA isolated from
      HTLV-1-infected cells might induce the production of proinflammatory cytokines
      and activate T helper (Th)1, and not Th2-immune response. If this finding is
      further confirmed, this study may have impact on investigations on the
      pathogenesis of HAM-TSP and the inflammatory response involved in this disease.

PMID- 30229664
TI  - Characterization of a New HIV-1 CRF01_AE/B Recombinant Virus Form Among Men Who
      Have Sex with Men in Shanghai, China.
AB  - To date, there are 16 types of CRF01_AE/B circulating recombinant forms
      identified, and most of them are distributed in Asian countries such as China,
      Malaysia, and Singapore. Previous HIV molecular epidemiological surveys showed
      that CRF01_AE (27.6%) and B (9.6%) subtypes are predominant strains in mainland
      of China. At the same time, the HIV-1 virus spreads faster in the men who have
      sex with men (MSM) population than in other risk groups. In Shanghai district,
      ~66.0% of newly reported cases were infected through homosexual transmission. In
      this study, we report a novel recombinant strain of CRF01_AE/B. The near full
      length genome phylogenetic tree showed that the strain clustered with the
      CRF01_AE reference sequence and placed in the peripheral position within the
      branch of the CRF01_AE strain. Subregional evolutionary results indicated that
      the CRF01_AE subtype was derived from cluster 4 of CRF01_AE, which is mainly
      distributed in northern China. The subtype B was correlated with the U.S./Europe
      B, which are widely prevalent in the Chinese MSM population. In recent years, a
      large number of recombinant forms between CRF01_AE and B strains are continuously
      emerging in China. Therefore, understanding the current epidemic recombinant
      forms will have significant implications for prevention and treatment of
      HIV/AIDS.

PMID- 30229665
TI  - Using Rasch analysis to investigate the validity of the Everyday Discrimination
      Scale in a national sample.
AB  - The Everyday Discrimination Scale (EDS) is a widely used measure of
      discrimination. Rasch analysis was used to examine the psychometric properties of
      the EDS based on a national sample ( N = 2666). Items largely fit the Rasch model
      and yielded excellent separation and item reliability. However, severe floor
      effects were observed. Implications are discussed for use of the scale in
      populations that experience low levels of discrimination. An ordinal-to-interval
      conversion table for the EDS is also provided.

PMID- 30229666
TI  - Monocyte and Alveolar Macrophage Skewing Is Associated with the Development of
      Pulmonary Arterial Hypertension in a Primate Model of HIV Infection.
AB  - We investigated the relationship of monocytes, alveolar, and tissue-resident
      macrophage populations and the development of pulmonary arterial hypertension
      (PAH) in a nonhuman primate model of HIV infection. A prospective study of simian
      immunodeficiency virus-associated pulmonary arterial hypertension (SIV-PAH) was
      done. Rhesus macaques (n = 21) were infected with SIV. Blood, bronchoalveolar
      lavage fluid (BALF), and lung tissue were analyzed for monocyte and macrophage
      phenotypes and inflammatory mediators. Serial right heart catheterizations were
      performed at three time points throughout the study to assess hemodynamic
      alterations and the development of PAH. All 21 animals showed similar courses of
      SIV infection with an increasing proinflammatory plasma environment. At 6 months
      postinfection (mpi), 11 of 21 animals developed SIV-PAH (mPAP <=25 mmHg; right
      ventricular systolic pressure [RVSP] <=36 mmHg). PAH+ animals had an increased
      frequency of proinflammatory, nonclassical monocytes (CD14dimCD16+) (p = .06) in
      the peripheral blood and CD14+CCR7-CD163-CD206+ macrophages (p = .04) in BALF
      compared with PAH- animals at 6 mpi. Increased frequencies of these monocyte and
      macrophage phenotypes correlated with elevated RVSP (p = .04; p = .03). In
      addition, PAH+ animals had greater frequencies of tissue resident inflammatory M1
      like CD68+STAT1+ (p = .001) and M2a-like CD68+STAT3+ macrophages (p = .003) and a
      lower frequency of anti-inflammatory M2c-like CD68+STAT6+ macrophages (p = .003)
      as well as fewer interleukin (IL)-10+ cells (p = .01). The results suggest that
      HIV-PAH is associated with skewing of monocytes and alveolar macrophages toward a
      proinflammatory, profibrotic phenotype. Furthermore, PAH+ animals may have
      diminished capacity to downregulate exaggerated chronic inflammation, as
      indicated by lower levels of IL-10 in PAH+ animals, contributing to disease
      progression.

PMID- 30229667
TI  - The effectiveness of backward walking as a treatment for people with gait
      impairments: a systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate the effectiveness of backward walking in the treatment
      of people with gait impairments related to neurological and musculoskeletal
      disorders. DESIGN: Systematic review and meta-analysis of randomized and quasi
      randomized control studies. DATA SOURCES: Searched from the date of inception to
      March 2018, and included PubMed, Scopus, Cochrane Library, PEDro, CINAHL, and the
      MEDLINE databases. METHODS: Investigating the effects of backward walking on
      pain, functional disability, muscle strength, gait parameters, balance,
      stability, and plantar pressure in people with gait impairments. The PEDro scale
      was used to assess the quality. Similar outcomes were pooled by calculating the
      standardized mean difference. RESULTS: Of the 21 studies (neurological 11 and
      musculoskeletal 10), 635 participants were included. The average PEDro score was
      5.4/10. The meta-analysis demonstrated significant standardized mean difference
      values in favour of backward walking, with conventional physiotherapy treatment
      for two to four weeks to reduce pain (-0.87) and functional disability (-1.19)
      and to improve quadriceps strength (1.22) in patients suffering from knee
      osteoarthritis. The balance and stability in cases of juvenile rheumatoid
      arthritis, and gait parameters and muscle strength in anterior cruciate ligament
      injury improved significantly when backward walking was included as an exercise.
      There was no significant evidence in favour of backward walking in any of the
      other conditions. CONCLUSION: The systematic review and meta-analysis suggests
      that backward walking with conventional physiotherapy treatment is effective and
      clinically worthwhile in patients with knee osteoarthritis. Insufficient evidence
      was available for the remaining gait impairment conditions and no conclusions
      could be drawn.

PMID- 30229668
TI  - Near Full-Length Genome Sequence of a Novel HIV-1 Second-Generation Recombinant
      Form (CRF01_AE/CRF07_BC) Detected Among Men Who Have Sex with Men in Tianjin,
      China.
AB  - In recent years, men who have sex with men (MSM) have been the most affected
      population with fastest growing human immunodeficiency virus (HIV) prevalence in
      China. In our study, a novel CRF01_AE/07_BC HIV-1 recombinant form (TJIH0069),
      with four unique breakpoints in the pol, vpr, and nef gene regions, was
      identified among MSM in Tianjin City in north China. The CRF01_AE regions
      (regions I, III, and V) of the recombinant are all clustered together with a
      previously described sequence (HQ215555), which was exclusively circulating among
      MSM in Shijiazhuang city of Hebei Province in north China. The CRF07_BC regions
      (II and IV) are clustered with BJ070032 and JX960600, which were discovered from
      MSM population in north China. The continuous emergence of a similar pattern of
      recombinant strain between the two MSM-adapted existing circulating recombinant
      forms (CRFs) highlights the importance to monitor potential new CRFs for early
      and precise control and prevention.

PMID- 30229669
TI  - Genetic Diversity and Drug Resistance of HIV-1 Circulating in North Sulawesi,
      Indonesia.
AB  - Manado, the capital city of North Sulawesi, is a unique region in Indonesia
      because of its religion. We collected peripheral blood samples from 63
      individuals on antiretroviral therapy. The amplification of viral genomic
      fragments, viral subtyping, detection of HIV drug resistance-associated mutations
      (DRAMs), and phylogenetic analyses were performed. Viral subtyping revealed that
      the most prevalent HIV type 1 (HIV-1) subtype/circulating recombinant form (CRF)
      was CRF01_AE (84.1%), followed by subtype B (6.8%) and recombinants between
      CRF01_AE and CRF02_AG (4.5%). Although no major DRAMs were present in protease
      genes, they were detected in reverse transcriptase (RT) genes. Nine of 38 samples
      (23.7%) had major DRAMs against nucleoside RT inhibitors (NRTIs) and/or non
      NRTIs. The results of phylogenetic analyses indicated that CRF01_AE in North
      Sulawesi is related to that in Bali. Therefore, Bali may play an important role
      in circulating CRF01_AE in North Sulawesi.

PMID- 30229671
TI  - A Meta-Analysis of the Effect of Multisession Transcranial Direct Current
      Stimulation on Cognition in Dementia and Mild Cognitive Impairment.
AB  - There have been increasing efforts to investigate the effects of neuromodulation
      techniques, such as transcranial direct current stimulation (tDCS), on cognitive
      impairment in dementia and related conditions. In this systematic review and meta
      analysis, we assessed the efficacy of multisession anodal tDCS compared with sham
      stimulation for improving global cognition and specific cognitive domains in both
      Alzheimer's disease and mild cognitive impairment. Eight articles meeting the
      criteria for inclusion in the meta-analysis were selected. Five studies used the
      Mini-Mental State Examination to examine mild cognitive impairment and dementia.
      In a fixed-effect model, there was a mean difference in the change score of -0.13
      points. Three trials for dementia using the Alzheimer's Disease Assessment Scale
      Cognition showed a mean difference of -0.53 points. At present, there is a lack
      of clear evidence concerning the efficacy of multisession anodal tDCS due to the
      small number of studies and different measures used. This underscores the need
      for further investigations using larger samples and common outcome measures.

PMID- 30229670
TI  - Cryotherapy for the Treatment of Chronic Rhinitis: A Qualitative Systematic
      Review.
AB  - BACKGROUND: Chronic rhinitis impacts 60 million Americans and is associated with
      significant costs for patients. Although medical treatments are first line, some
      patients require surgical intervention such as vidian or posterial nasal
      neurectomy. Previous reviews have investigated the role of surgical management in
      chronic rhinitis, but none have investigated a longstanding treatment with recent
      interest: cryotherapy. OBJECTIVE: To identify the safety, efficacy, and
      durability of treatment response of cryotherapy in treating chronic rhinitis.
      METHODS: A systematic literature review was performed to identify studies that
      investigated the utility of cryotherapy in chronic rhinitis. Only studies with
      the primary objective of assessing the efficacy of cryotherapy on chronic
      rhinitis were included. Patients were classified as allergic rhinitis,
      nonallergic rhinitis (vasomotor rhinitis), or mixed rhinitis using the original
      author's criteria. Data were extracted regarding reported complications,
      treatment efficacy, and length of follow-up. RESULTS: A total of 110 abstracts
      were identified, of which 15 were included in this review. Epistaxis and nasal
      obstruction were commonly reported complications. No serious adverse events were
      reported. For obstructive symptoms, "reduced" symptoms were reported in 63.4% to
      100% of patients. In regard to rhinorrhea, reports of reduced symptoms were
      experienced from 77% to 100% of patients. Seven studies used only patient
      reported improvements without stratifying results based on symptom type; general
      improvements ranged from 67% to 100%. Nine studies noted symptom improvement in
      nonallergic cohorts ranging from 67% to 97.5% of patients. Four studies noted
      improvement in allergic cohorts ranging from 63.4% to 80% of patients. Two
      studies noted improvement in patients with mixed pictures ranging from 92.5% to
      100%. CONCLUSIONS: Although cryotherapy appears safe and efficacious,
      heterogeneous past investigations with low-quality evidence make strong, evidence
      based recommendations difficult to make. Further study with validated metrics and
      controlled populations is certainly warranted and should be encouraged.

PMID- 30229672
TI  - The optical coherence tomography angiography findings of rheumatoid arthritis
      patients taking hydroxychloroquine.
AB  - PURPOSE: The aim of this study is to measure retinal vessel density and thickness
      of the macula by optical coherence tomography angiography in patients with
      rheumatoid arthritis taking hydroxychloroquine. METHODS: The study included 40
      patients with rheumatoid arthritis taking hydroxychloroquine and 20 age-, gender
      , and axial length-matched control subjects. Patients were divided into two
      groups according to the duration of hydroxychloroquine use. Twenty four of the
      patients were taking hydroxychloroquine for more than 5 years (Group 1), and the
      rest of 16 were taking hydroxychloroquine for less than 5 years (Group 2). A
      total of 20 age- and gender-matched volunteers with similar axial length were
      selected as Group 3. All of the patients underwent optical coherence tomography
      angiography, and 3 mm * 3 mm scanning mode was chosen for analyzing vascular
      density and morphological characteristics on the choriocapillaris layer. In
      addition, Humphrey visual field 10-2 was evaluated in each subject. RESULTS: The
      temporal deep vascular density was measured as 48.13% +/- 8.5% in Group 1, 54.42%
      +/- 10.3% in Group 2, and 60.35% +/- 13.1% in Group 3. Deep temporal and deep
      hemi-inferior vascular density was significantly lower in Group 1 in comparison
      with Group 3 (p = 0.041 and p = 0.046, respectively). Visual field testing was
      normal in all patients. CONCLUSION: The optical coherence tomography angiography
      findings showed that the parafoveal deep temporal and deep hemi-inferior vascular
      plexus density was reduced in patients taking hydroxychloroquine for more than 5
      years despite having normal perimetry. This observation, which can be obtained
      only through optical coherence tomography angiography, may be relevant to the
      early findings of hydroxychloroquine toxicity.

PMID- 30229673
TI  - Intestinal mucosa develops in a sex-dependent manner in Japanese quail (Coturnix
      japonica) fed Saccharomyces cerevisiae.
AB  - 1. The aim of study was to investigate whether the impact of the yeast
      Saccharomyces cerevisiae on the histological structure of the intestine,
      innervation of the small intestine wall, and basal biochemical serum parameters
      in Japanese quail was sex dependent. 2. One-day-old healthy male and female
      Japanese quail were fed either a basal diet containing no yeast (control group)
      or the basal diet plus 1.5% (15 g/kg of diet) of yeast (S. cerevisiae inactivated
      by drying). Samples from the duodenum and jejunum were taken from each bird at
      the age of 42 days. Blood samples were collected at this age and the
      concentrations of glucose, total protein, creatinine, uric acid, lipid profile
      (total cholesterol, low density lipoproteins (LDL), high density lipoproteins
      (HDL), and triacylglycerols (TG)), alanine aminotransferase (ALAT), aspartate
      aminotransferase (AspAT), lactate dehydrogenase (LDH), amylase (AMY), calcium,
      phosphorus, and iron were determined. 3. Female quail fed diets supplemented with
      yeast had significantly lower total cholesterol and amylase activity than the
      control females. The concentration of HDL was higher in the male quail than in
      the females, irrespective of the treatment. An opposite effect was observed in
      LDL. The diet treatments influenced the activity of AspAT, which was
      significantly less in the male quail fed diets with 1.5% yeast. 4.
      Supplementation with S. cerevisiae increased the myenteron, submucosa, and mucosa
      thickness, villus length and thickness and size of absorptive surface, while the
      number of villi and enterocytes were decreased in the duodenum in males. Female
      quail showed an increased absorptive surface in the jejunum. The Meissner
      (submucosal) plexuses were influenced by the feeding and sex to a greater extent
      than the Auerbach plexus (in the muscularis propria). 5. The results demonstrated
      that S. cerevisiae (1.5%) in the diet caused significant positive effects in
      Japanese quail, exerting an effect on the morphology of the small intestine in a
      sex-dependent manner.

PMID- 30229674
TI  - Limitations in contemporary self-reported medication adherence questionnaires:
      the concept and design of the General Medication Adherence Scale (GMAS)
      originating from a developing country.

PMID- 30229675
TI  - The double edge sword of John Henryism: Impact on patients' health in the
      People's Republic of China.
AB  - The People's Republic of China has experienced extraordinary economic growth,
      which is associated with increases in chronic health stressors. We examined the
      impact of John Henryism-a coping mechanism-on various health indicators in a
      sample of patients ( n = 642) in China. John Henryism significantly related to
      increased medical adherence [Formula: see text] and health-promotional behaviors
      [Formula: see text]. John Henryism predicted several indicators of psychological
      health through social support. John Henryism was also related to increased
      alcoholism [Formula: see text]. The findings highlight the complexity and
      paradoxical implications of John Henryism on health. Implications are discussed
      in relation to China's epidemiological and age demographic shifts.

PMID- 30229676
TI  - An Insertion of Seven Amino Acids in the Envelope Cytoplasmic Tail of HIV-2
      Selected During Disease Progression Enhances Viral Replication.
AB  - The cytoplasmic tail (CT) of the HIV-2 envelope glycoprotein (Env) includes amino
      acid (aa) sequences that are similar to lentiviral lytic peptides (LLP) described
      in other lentiviruses. Within the putative LLP-2 region, we previously observed
      insertions of 3 or 7 aa in sequences deduced from plasma viral RNA of symptomatic
      HIV-2-infected individuals. Based on these observations, we reproduced the
      insertions in a molecular clone to assess their impact on replicative fitness and
      cell death in vitro. Using a molecular clone of the HIV-2ROD reference strain,
      site-directed mutagenesis experiments allowed the generation of plasmids with the
      insertion L791TAI or L791QRALTAI in the Env protein. The clone with 7 aa
      insertion enhanced viral release 8 to 11 times in infected T cells and cell
      viability was impaired by more than 20%, compared with the wild-type HIV-2ROD
      virus. The effect of the 3 aa insertion was milder, with a nonsignificant trend
      to enhance viral replication and cell death compared with the wild-type virus.
      Interestingly, the insertions in the Env proteins did not induce a significant
      increase of viral infectivity, as revealed by the infectivity assay using TZM-bl
      cells. The insertions in the Env CT observed in vivo from disease progressors
      may, therefore, be involved in the higher viral load observed in these
      individuals. This study may open the way to the development of a prognostic
      marker related to the HIV-2 infection progression.

PMID- 30229677
TI  - Lessons From the Development of the Immune Checkpoint Inhibitors in Oncology.
AB  - Immunotherapies are becoming increasingly important in the treatment
      armamentarium of a variety of malignancies. Immune checkpoint inhibitors are the
      most representative drugs receiving regulatory approval over the past few years.
      In a recent study published in Clinical Cancer Research, we demonstrated that
      these agents are being developed faster than other prior anticancer therapies.
      All checkpoint inhibitors received priority review, being granted with at least
      one Food and Drug Administration expedited program. Hence, some of them are
      getting marketing approval after preliminary trials. The model continues to rely
      on phase I trials, designed with traditional models for dose definition, although
      a substantial number of patients are treated during the dose expansion cohorts.
      We demonstrated that efficacy and safety are reasonably predicted from the dose
      finding portion of phase I trials with these agents, assuring a low treatment
      related mortality for patients throughout the development process. In this
      article, we further discuss and summarize these findings and update some recent
      approval information for immune checkpoint inhibitors.

PMID- 30229678
TI  - Efficacy and Safety of Appetite-Stimulating Medications in the Inpatient Setting.
AB  - BACKGROUND: Hospitalized patients are subject to acute illness and stress which
      may impact appetite or weight. Loss of appetite may lead to increased morbidity
      or mortality. Medications such as dronabinol, megestrol, and mirtazapine are used
      for weight gain in the outpatient setting; however, there is limited information
      about safety or effectiveness when initiated inpatient. OBJECTIVES: To analyze
      the effectiveness and safety of appetite-stimulating medications in hospitalized
      patients. METHODS: This was a retrospective cohort study of hospitalized patients
      initiated on dronabinol, megestrol, or mirtazapine for appetite. The primary
      outcome was change in meal intake between drug initiation and discontinuation.
      Secondary outcomes included documented improvement in appetite, change in weight
      and various laboratory parameters, and incidence of adverse effects. RESULTS: A
      total of 38 patients met inclusion criteria, and mirtazapine was most commonly
      used (42%). There was no significant difference between groups of appetite
      stimulating medications with regard to mean change in meal intake, weight,
      albumin, or documented improvement in diet. Within groups, each agent showed
      numerical improvement in percentage meal intake, with a mean change from
      initiation to discontinuation of 17.12%. Almost half (48%) of the patients
      experienced improvement in diet after the start of medications. No serious
      adverse effects were observed. Conclusion and Relevance: In inpatients, there was
      no difference in change in meal intake or weight between dronabinol, megestrol,
      or mirtazapine, but they may show numerical improvements in meal intake. To our
      knowledge, this is the first study to evaluate the use of dronabinol, megestrol,
      and mirtazapine initiated in the inpatient setting.

PMID- 30229679
TI  - Teaching Residents Frontal Sinus Anatomy Using a Novel 3-Dimensional
      Conceptualization Planning Software-Based Module.
AB  - BACKGROUND: The Frontal Sinus Masterclass (FSMC) is an effective method for
      teaching frontal sinus anatomy. A third party developed new software using the
      same 3-dimensional building block concept. The authors sought to determine
      whether the use of the software for the educational module yielded similar
      results to the original FSMC, which used wooden blocks. METHODS: The study was
      performed at a sinus course for residents. A precourse test assessed the ability
      to decipher frontal sinus anatomy prior to the course. Computed tomography (CT)
      scans of the sinuses were evaluated in triplanar view, and participants attempted
      to reconstruct the anatomy using the new software. Subsequently, the course
      instructor explained the anatomy and showed a short corresponding surgical video
      of the frontal sinusotomy. Cases progressed in anatomical difficulty and
      inflammatory load. A postcourse test determined knowledge after the course.
      RESULTS: In sum, 50 residents completed the pre- and postcourse tests. Overall
      scores increased from 60.5% to 65.2% ( P = .004). Subanalysis also demonstrated
      improved ability to locate the frontal drainage pathway from 32.5% to 46% ( P =
      .011) and label the frontal recess cell structures from 64% to 67.6% ( P = .045).
      CONCLUSION: There is minimal literature on proven methods for teaching frontal
      sinus anatomy. Objectively, participants of the modified FSMC simulation training
      using new software improved their ability to recognize cells of the frontal
      recess on CT scans. They especially exhibited better localization of the frontal
      sinus drainage pathway. Subjectively, participants reported benefit from the
      course and felt they would be better surgeons.

PMID- 30229680
TI  - Making Triage Decisions for the Acute Community Care Program: Paramedics Caring
      for Urgent Health Problems in Patients' Homes.
AB  - The Acute Community Care Program (ACCP) initiative sends specially trained
      paramedics to evaluate and treat patients with urgent care problems in their
      residences during evening hours. ACCP safety depends on making appropriate triage
      decisions from patients' reports during phone calls about whether paramedics
      could care for patients' urgent needs or whether they require emergency
      department (ED) services. Furthermore, after ACCP paramedics are on scene,
      patients may nonetheless need ED care if their urgent health problems are not
      adequately treated by the paramedic's interventions. To train clinical staff
      participating in all aspects of ACCP, including these triage decisions, ACCP
      clinical leaders developed brief vignettes: 27 represented initial ACCP triage
      decisions and 10 the subsequent decision to send patients to EDs. This report
      describes findings from an online survey completed by 24 clinical staff involved
      with ACCP triage. Clinical vignettes could be useful for staff training and
      quality control in such paramedic initiatives.

PMID- 30229681
TI  - Relationships among resilience, self-esteem, and depressive symptoms in Chinese
      adolescents.
AB  - This study explored the relationships among resilience, self-esteem, and
      depressive symptoms in Hong Kong Chinese adolescents. We selected a stratified
      random sample of 1816 Form 1 students from all 18 districts of Hong Kong. This
      study revealed that about 21 percent adolescents are experiencing some depressive
      symptoms. Our results contribute novel findings to the literature showing that
      resilience is a strong indicator of adolescents at a higher risk of depression
      and increasing adolescents' resilience to psychological distress is crucial to
      enhance their mental well-being. It is crucial to develop interventions that can
      enhance resilience and promote positive mental well-being among adolescents.

PMID- 30229682
TI  - Like a Fish out of Water: Managing Chronic Pain in the Urban Safety Net.
AB  - The subjective nature of pain has always rendered it a point of entry for power
      and corresponding stratifying processes within biomedicine. The opioid crisis has
      further exacerbated these challenges by increasing the stakes of prescribing
      decisions for providers, which in turn has resulted in greater treatment
      disparities. Using the theoretical frame of cultural health capital (CHC) to
      account for these disparities in pain management as they unfold at both the macro
      and the microlevel, we present findings from an interdisciplinary study of two
      complex care management programs in urban safety-net hospitals that serve high
      utilizing patients. CHC, which considers the ways in which patient-provider
      interactions reflect and often reinforce broader social inequities, allows for a
      consideration of power as it circulates through and beyond the patient-provider
      encounter. Within the current sociopolitical era of pain management, attention
      must be paid to the stratifying processes that structure how suffering is
      addressed.

PMID- 30229683
TI  - Banxia Xiexin Decoction Is Effective to Prevent and Control Irinotecan-Induced
      Delayed Diarrhea in Recurrent Small Cell Lung Cancer.
AB  - BACKGROUND: Irinotecan (CPT-11) can be used as a first-line therapeutic drug
      against extensive-stage small cell lung cancer (SCLC); it can also be used in
      second-line treatment for SCLC. CPT-11-induced delayed diarrhea restricts its
      clinical application. This study aimed to confirm whether Banxia Xiexin decoction
      was effective in preventing and controlling CPT-11-induced delayed diarrhea.
      METHODS: A total of 27 patients with recurrent SCLC undergoing chemotherapy
      regimens including CPT-11 were enrolled for the study. UGT1A1*28, UGTlAl*6,
      ABCB1*2, and SLCO1B1*15 gene polymorphisms were detected. If delayed diarrhea
      occurred in the first cycle of chemotherapy, Banxia Xiexin decoction was orally
      administered for 5 consecutive days starting 1 day before the second cycle of
      chemotherapy to prevent and control the delayed diarrhea. The objective response,
      overall survival, and toxicity were recorded. RESULTS: Complete response, partial
      response, and stable disease were observed in none, 6, and 10 patients,
      respectively. Delayed diarrhea occurred in 6 patients, and 4 of 5 patients were
      relieved or controlled using Banxia Xiexin decoction. The median overall survival
      was 6 months. CONCLUSION: Banxia Xiexin decoction appeared to prevent and control
      delayed diarrhea induced by CPT-11 in this small observational study, and further
      study with a larger sample size, including potentially randomized trials, is
      suggested.

PMID- 30229686
TI  - Editorial.

PMID- 30229684
TI  - Qualitative Consumer Research on Acceptance of Long-Acting Pre-Exposure
      Prophylaxis Products Among Men Having Sex with Men and Medical Practitioners in
      the United States.
AB  - Pre-exposure prophylaxis (PrEP) with oral Truvada(r) prevents HIV infection.
      However, the adherence to pill taking required for efficacy has sparked interest
      in developing new antiretroviral delivery systems that decrease such demands.
      Long-acting formulations, such as injections and implants, represent promising
      options that require less frequent adherence. It is important, however, that
      development of these new modalities be driven by understanding of the value seen
      in them by target users to maximize their uptake. To identify the key product
      features that impact user acceptance, we used a three-phase marketing research
      approach. In this study, we describe the results of the first-phase, qualitative
      focus group research performed in Chicago and San Francisco that explored
      subjective perceptions of oral versus alternative PrEP modalities among men
      having sex with men (MSM) and medical practitioners caring for MSM. Data revealed
      that potential value in long-acting PrEP lies more in simplifying the lives of
      users rather than in making them more confident in their adherence. The results
      provide an important guidance for designing and promoting these future long
      acting products to enhance their contribution to increasing the current limited
      uptake of PrEP that will better stem the HIV epidemic.

PMID- 30229685
TI  - Mechanism of enhanced oral absorption of akebia saponin D by a self
      nanoemulsifying drug delivery system loaded with phospholipid complex.
AB  - Akebia saponin D (ASD) exhibits a variety of pharmacological activities, such as
      anti-osteoporosis, neuroprotection, hepatoprotection, but has poor oral
      bioavailability. A self-nanoemulsifying drug delivery system loaded with akebia
      saponin D - phospholipid complex (APC-SNEDDS) (composition: Peceol: Cremophor(r)
      EL: Transcutol HP: ASD: phospholipid; ratio: 10:45:45:51:12.3, w:w:w:w:w) was
      first developed to improve the oral absorption of saponins and it was found to
      significantly enhance ASD's oral bioavailability by 4.3 - fold (p < .01). This
      study was conducted to elucidate the mechanism of enhanced oral absorption of ASD
      by the drug delivery system of APC-SNEDDS. The aggregation morphology and
      particle size of ASD and APC-SNEDDS prepared in aqueous solutions were determined
      by transmission electron microscope and particle size analyzer, respectively.
      Stability of ASD and APC-SNEDDS in gastrointestinal luminal contents and mucosa
      homogenates were also explored. The differences of in situ intestinal
      permeability of ASD and APC-SNEDDS were compared. APC-SNEDDS reduced the
      aggregation size from 389 +/- 7 nm (ASD) to 148 +/- 3 nm (APC-SNEDDS). APC-SNEDDS
      increased the remaining drug in large intestine luminal contents from 47 +/- 1%
      (ASD) to 83 +/- 1% (APC-SNEDDS) during 4 h incubation. APC-SNEDDS provided an 11
      fold increase in Ka value and an 11-fold increase in Peff value compared to ASD.
      In summary, APC-SNEDDS improved ASD's oral bioavailability mainly by increasing
      membrane permeability, destroying self-micelles and inhibiting the intestinal
      metabolism.

PMID- 30229688
TI  - Family Nursing Network: Dr. Susan Sullivan-Bolyai Joins Journal of Family Nursing
      Editorial Board.

PMID- 30229689
TI  - Level of human development is associated with cervical cancer stage at diagnosis.
AB  - The objective was to describe the cervical cancer cases in Brazil by the age
      group and stage at diagnosis, and to associate them with the human development
      index (HDI), where the women live. This was a retrospective study that used data
      from the Brazilian hospital-based cancer registry from 2005 to 2014. The data
      were accessed by 5-year age/groups and the federal units. The association between
      the proportion of cases at Stage I and HDI was estimated in an adjusted linear
      regression analysis. Among the staged cases, the proportions of cases diagnosed
      at FIGO Stage I, II, III and IV were 21.2%, 30.7%, 39.9% and 8.2%, respectively.
      The cases were diagnosed mostly in women aged 45-49 years. There was a
      significant increase in the proportion of Stage I cases with an increasing HDI
      (coefficient, 0.46; 95% confidence interval, 0.17-0.76). In conclusion, most of
      the cases were diagnosed at late stages. The stage at the diagnosis was
      associated with the human development level. Impact Statement What is already
      known on this subject? The stage at diagnosis varies according to the level of
      organisation of the cancer control programme. It is expected that in well
      developed programmes there will be a shift to an early stage diagnosis. What the
      results of this study add? The stage at a diagnosis was associated with the human
      development level where the women live in Brazil, where most cases were diagnosed
      at the late stages. What the implications are of these findings for clinical
      practice and/or further research? This analysis can help with better planning
      strategies for cancer control. Regional strategies would improve the efficiency
      of cancer care interventions in countries with large socioeconomic disparities.

PMID- 30229690
TI  - Right Ventricular Function in Left Heart Disease: Relevance to the Mitral Valve.
AB  - Right ventricular (RV) function is an independent prognostic factor for short-
      and long-term outcomes in cardiac surgical patients. Patients with mitral valve
      (MV) disease are at increased risk of RV dysfunction before and after MV
      operations. Yet RV function is not part of criteria for decision making or risk
      stratification in this setting. The role of MV disease in the development of
      pulmonary hypertension (PHTN) and the ultimate impact of PHTN on RV function have
      been well described. Nonetheless, there are other mechanisms by which MV disease
      and MV surgery affect RV performance. Research suggests that PHTN may not be the
      most important determinant of RV dysfunction. Both RV dysfunction and PHTN have
      independent prognostic significance. This review explores the unique anatomic and
      functional features of the RV and the pathophysiologic and prognostic
      implications of RV dysfunction in patients with MV disease in the perioperative
      period.

PMID- 30229691
TI  - Baseline markers of inflammation, lipids, glucose, and Dietary Inflammatory Index
      scores do not differ between adults willing to participate in an intensive
      inflammation reduction intervention and those who do not.
AB  - BACKGROUND: Chronic inflammation is associated with numerous chronic diseases and
      can be managed with diet. AIM: The purpose of this study was to examine
      differences in baseline characteristics and plasma inflammation levels between
      two groups of participants that participated in an intensive, lifestyle
      intervention or a remotely delivered intervention. This work also assessed the
      association between Dietary Inflammatory Index (DII)(r) scores and participants'
      inflammatory and metabolic biomarkers at baseline. METHOD: Ninety-five
      participants (61 intervention, 34 control) chose to enroll in either a 12-month
      intervention consisting of a face-to-face nutrition, physical activity, and
      stress management intervention or a remotely-delivered intervention (control
      group) focusing on general cancer prevention. The intervention group met at the
      University of South Carolina for classes and the control group had materials
      emailed to them. A quantile regression was used to compare participants' high
      sensitivity C-reactive protein and interleukin-6 levels. Multiple linear
      regression was used to determine the association between DII scores and
      biomarkers. RESULTS: There were significant differences in age, body mass index,
      body fat percentage, and blood pressure between groups, but there were no
      differences in levels of inflammatory biomarkers. Values of interleukin-6 at the
      90th percentile of its distribution were 8.31 pg/ml higher among those in DII
      quartile 4 compared with quartile 1 ( p = 0.02). All other outcomes were not
      significant. CONCLUSION: Given similar levels of inflammatory biomarkers,
      participants opting for the control group would also have benefited from a more
      intensive lifestyle intervention focusing on reducing inflammation.

PMID- 30229692
TI  - Preparation, Optimization, and in vitro - in vivo Evaluation of Febuxostat
      Ternary Solid Dispersion.
AB  - The research aimed to prepare febuxostat (FEB) solid dispersion via solvent
      evaporation. Optimized solid dispersion composed of FEB, Polyvinylpyrrolidone
      (PVP K30) and poloxamer at ratio of 1:3:3 was characterized. Powder X-ray
      diffraction(XRD) and Differential scanning calorimetry (DSC) indicated FEB was
      transformed from crystalline into amorphous state in solid dispersion and
      Scanning electron microscopy (SEM) revealed the morphology. Fourier transform
      infrared spectroscopy (FT-IR) suggested the interactions formed between FEB and
      polymers. A remarkable increase was observed of the optimized formulation in
      saturation solubility, dissolution studies (96.17+/-0.79% in pH 6.0) and
      bioavailability (Cmax 18.25+/-2.44 vs. 7.72+/-0.48 MUg/mL and AUC0-infinity
      53.62+/-7.63 vs. 34.76+/-2.45 MUg.h/mL). Besides, the FEB solid dispersion showed
      great stability after 90 days storage. Thus, the present study supports the
      rationality of PVP K30 and poloxamer188 as co-carriers for the preparation of FEB
      solid dispersion.

PMID- 30229693
TI  - Trends in African Americans' Attitudes and Behaviors About Living Donor Kidney
      Transplantation.
AB  - BACKGROUND:: Due to marginal efforts to increase living donor kidney
      transplantation, it is unclear whether interventions to improve African
      Americans' interest and pursuit of living donation should be tailored to address
      patients' exposure to or familiarity with dialysis or transplant settings.
      DESIGN, SETTING, AND PARTICIPANTS:: We conducted a cross-sectional secondary
      analysis of baseline data from 3 separate randomized clinical trials among
      African Americans with varying degrees of experience with dialysis or
      transplantation (predialysis, on dialysis but not on transplant list, and on
      transplant wait-list) settings. METHODS:: Interest in living donation was
      described using a 0 to 10 scale and pursuit of living donor kidney
      transplantation by achievement of at least 1 pursuant behavior. In multivariable
      logistic regression analyses, we assessed the association of knowledge, health
      literacy, and trust in health care with interest in or pursuit of living
      donation. RESULTS:: Interest among the 3 study cohorts was high (predialysis,
      62.9%; dialysis, 67.4%; and transplant wait-list, 74.2%). The dialysis and
      transplant wait-list study cohorts pursued living donation more readily than
      those not on dialysis (73%, 92%, and 45%, respectively). Interest and pursuit
      were not statistically significantly associated with knowledge, health literacy,
      or the 3 factors reflecting medical mistrust. CONCLUSION:: Interest and pursuit
      of living donation were greater among study participants with greater exposure to
      dialysis or transplant settings. Efforts to promote patients' early interest and
      pursuit of living donor transplants may consider novel strategies to educate
      patients with less experience about the benefits of living donor kidney
      transplantation.

PMID- 30229694
TI  - miRNA-376c-3p Mediates TWIST-1 Inhibition of Bone Marrow-Derived Stromal Cell
      Osteogenesis and Can Reduce Aberrant Bone Formation of TWIST-1 Haploinsufficient
      Calvarial Cells.
AB  - Key transcription factors, which activate or repress master gene regulators and
      signaling pathways, tightly regulate self-renewal and cell lineage
      differentiation of bone marrow-derived stromal cells (BMSC). Among these factors
      is the basic helix-loop-helix transcription factor Twist-related protein 1 (TWIST
      1), which is important in BMSC self-renewal, life span, and differentiation.
      Another layer of gene regulation comes from microRNAs (miRNAs). miRNAs are short
      noncoding RNAs that interfere with translation of specific target mRNAs and
      thereby regulate diverse biological processes, including BMSC lineage commitment.
      However, little is known of how TWIST-1-regulated miRNAs control osteogenic
      commitment, and influence the fate of bone precursor cells. In this study, we
      have discovered a novel TWIST-1-regulated miRNA, miR-376c-3p. Reduced miR-376c-3p
      expression by a miR-376c-3p inhibitor or due to TWIST-1 haploinsufficiency
      promotes alkaline phosphatase (ALP) activity, mineral deposition, and expression
      of osteoblast-associated genes in BMSC and calvarial cells. Conversely,
      overexpression of miR-376c-3p using a miR-376c-3p mimic inhibited BMSC
      proliferation and the osteogenic potential of BMSC and TWIST-1 haploinsufficient
      calvarial cells. This was demonstrated by a decrease in insulin growth factor 1
      receptor (IGF1R) levels, Akt signaling, ALP activity, mineral deposition, and
      expression of osteoblast-associated genes. Thus, miR-376c-3p reduces IGF1R/Akt
      signaling in BMSC and is one mechanism by which osteogenesis may be inhibited.
      Overall, we have identified miR-376c-3p as a TWIST-1-regulated miRNA, which plays
      an important role in the osteogenesis of bone precursor cells and can mediate
      TWIST-1 inhibition of osteogenesis. Furthermore, overexpression of miRNA-376c-3p
      in TWIST-1 haploinsufficient calvarial cells can decrease the aberrant
      osteogenesis of these cells, which contributes to increased calvarial bone volume
      and premature fusion of the coronal sutures.

PMID- 30229695
TI  - A Bayesian adaptive phase II clinical trial design accounting for spatial
      variation.
AB  - Conventional phase II clinical trials evaluate the treatment effects under the
      assumption of patient homogeneity. However, due to inter-patient heterogeneity,
      the effect of a treatment may differ remarkably among subgroups of patients.
      Besides patient's individual characteristics such as age, gender, and biomarker
      status, a substantial amount of this heterogeneity could be due to the spatial
      variation across geographic regions because of unmeasured or unknown spatially
      varying environmental and social exposures. In this article, we propose a
      hierarchical Bayesian adaptive design for two-arm randomized phase II clinical
      trials that accounts for the spatial variation as well as patient's individual
      characteristics. We treat the treatment efficacy as an ordinal outcome and
      quantify the desirability of each possible category of the ordinal efficacy using
      a utility function. A cumulative probit mixed model is used to relate efficacy to
      patient-specific covariates and geographic region spatial effects. Spatial
      dependence between regions is induced through the conditional autoregressive
      priors on the spatial effects. A two-stage design is proposed to adaptively
      assign patients to desirable treatments according to each patient's spatial
      information and individual covariates and make treatment recommendations at the
      end of the trial based on the overall treatment effect. Simulation studies show
      that our proposed design has good operating characteristics and significantly
      outperforms an alternative phase II trial design that ignores the spatial
      variation.

PMID- 30229696
TI  - Quality of care for the dying across different levels of palliative care
      development: A population-based cohort study.
AB  - BACKGROUND:: There is a lack of knowledge about how the provision and
      availability of specialized palliative care relates to the quality of dying in
      hospital and community-based settings. AIM:: We aimed to explore the quality of
      care during last week of life in relation to different levels of palliative care
      development. DESIGN:: We investigated access to palliative care in Southern
      Sweden, where one region offers palliative care in accordance with European
      Association for Palliative Care guidelines for capacity, and the other region
      offers less developed palliative care. Data on approximately 12,000 deaths during
      2015 were collected from the Swedish Register of Palliative Care. The quality of
      care was investigated by region, and was measured in terms of assessment of oral
      health and of pain, and end-of-life conversation, companionship at death and
      artificial nutrition/fluid in the last 24 h. RESULTS:: The overall quality of
      care during last week of life was not consistently better in the region with
      fully developed palliative care compared with the less developed region. In fact,
      for patients dying in hospitals and community-based settings, the quality was
      statistically significantly better in the less developed region. The small
      proportion of patients who had access to specialized palliative care had superior
      quality of care during the last week of life as compared to patients in other
      care settings. CONCLUSION:: The capacity of specialized palliative care does not
      per se influence the quality of care during the last week of life for patients in
      other settings.

PMID- 30229697
TI  - How Do Actions Influence Attitudes? An Inferential Account of the Impact of
      Action Performance on Stimulus Evaluation.
AB  - Over the past decade, an increasing number of studies have shown that the
      performance of specific actions (e.g., approach and avoidance) in response to a
      stimulus can lead to changes in how that stimulus is evaluated. In contrast to
      the reigning idea that these effects are mediated by the automatic formation and
      activation of associations in memory, we describe an inferential account that
      specifies the inferences underlying the effects and how these inferences are
      formed. We draw on predictive processing theories to explain the basic processes
      underlying inferential reasoning and their main characteristics. Our inferential
      account accommodates past findings, is supported by new findings, and leads to
      novel predictions as well as concrete recommendations for how action performance
      can be used to influence real-world behavior.

PMID- 30229698
TI  - A spatial regression model for the disaggregation of areal unit based data to
      high-resolution grids with application to vaccination coverage mapping.
AB  - The growing demand for spatially detailed data to advance the Sustainable
      Development Goals agenda of 'leaving no one behind' has resulted in a shift in
      focus from aggregate national and province-based metrics to small areas and high
      resolution grids in the health and development arena. Vaccination coverage is
      customarily measured through aggregate-level statistics, which mask fine-scale
      heterogeneities and 'coldspots' of low coverage. This paper develops a
      methodology for high-resolution mapping of vaccination coverage using areal data
      in settings where point-referenced survey data are inaccessible. The proposed
      methodology is a binomial spatial regression model with a logit link and a
      combination of covariate data and random effects modelling two levels of spatial
      autocorrelation in the linear predictor. The principal aspect of the model is the
      melding of the misaligned areal data and the prediction grid points using the
      regression component and each of the conditional autoregressive and the Gaussian
      spatial process random effects. The Bayesian model is fitted using the INLA-SPDE
      approach. We demonstrate the predictive ability of the model using simulated data
      sets. The results obtained indicate a good predictive performance by the model,
      with correlations of between 0.66 and 0.98 obtained at the grid level between
      true and predicted values. The methodology is applied to predicting the coverage
      of measles and diphtheria-tetanus-pertussis vaccinations at 5 * 5 km2 in
      Afghanistan and Pakistan using subnational Demographic and Health Surveys data.
      The predicted maps are used to highlight vaccination coldspots and assess
      progress towards coverage targets to facilitate the implementation of more
      geographically precise interventions. The proposed methodology can be readily
      applied to wider disaggregation problems in related contexts, including mapping
      other health and development indicators.

PMID- 30229699
TI  - Clinical Phenomenology and Characteristics of Centenarians in Hospice.
AB  - OBJECTIVES: Little is known about the hospice experience of centenarians. As the
      population of centenarians is projected to increase, understanding their unique
      end-of-life needs will be important to inform delivery of quality end-of-life
      care. Our objective was to characterize the hospice experience of centenarians.
      METHODS: A retrospective single-institution cohort study of centenarians enrolled
      in hospice from January 1, 2015, to December 31, 2017, was conducted to collect
      demographic and clinical information. RESULTS: Seventeen centenarians, who
      comprised 1.4% of hospice admissions, had an average age of 102 years, were
      mostly female (71%) and widowed (76%), and all caucasian. Upon hospice admission,
      centenarians resided in nursing (8, 47%) and assisted living (4, 24%) residencies
      as well as at home (4, 24%) and in senior independent living (1, 6%). Sixty
      percent of centenarians died in a nursing home. The most common hospice admission
      diagnosis was dementia (35%). Median length of stay on hospice was 41 days
      (range: 16-85) for 15 persons who died or discharged live. CONCLUSIONS: In this
      group of centenarians, dementia was the most common condition for hospice
      enrollment. Slightly less than half resided in nursing homes on admission,
      although death occurred most frequently in a nursing home. Centenarians were
      generally able to remain out of the hospital at their time of death.

PMID- 30229700
TI  - The 'safe death': An ethnographic study exploring the perspectives of rural
      palliative care patients and family caregivers.
AB  - BACKGROUND:: In rural settings, relationships between place and self are often
      stronger than for urban residents, so one may expect that rural people would view
      dying at home as a major feature of the 'good death'. AIM:: To explore the
      concept of the 'good death' articulated by rural patients with life-limiting
      illnesses, and their family caregivers. DESIGN:: Ethnography, utilising open
      ended interviews, observations and field-notes. PARTICIPANTS:: In total, 12 rural
      (town and farm) patients with life-limiting illnesses, 18 family caregivers and 6
      clinicians, in the Snowy Monaro region of New South Wales, Australia,
      participated in this study over the course of the deaths of the patients.
      Interviews were transcribed and analysed with observational data using an
      emergent thematic process. RESULTS:: A 'safe death' was central to a 'good death'
      and was described as a death in which one could maintain (1) a connection with
      one's previous identity; (2) autonomy and control over decisions regarding
      management of end-of-life care and (3) not being overwhelmed by the physical
      management of the dying process. For all participants, the preferred place of
      death was the 'safe place', regardless of its physical location. CONCLUSION::
      Safety, in this study, is related to a familiar place for death. A home death is
      not essential for and does not ensure a 'good death'. We all have a
      responsibility to ensure all places for dying can deliver the 'safe death'.
      Future research could explore the inter-relationships between safety and
      preference for home or home-like places of death.

PMID- 30229701
TI  - Experimental assessment of biomechanical properties in human male elbow bone
      subjected to bending and compression loads.
AB  - This work discusses the biomechanical testing of 3 elbow bones, namely the
      humerus, ulna, and radius. There is a need to identify the mechanical properties
      of the bones at the organ level. The following tests were performed: 3-point
      bending, fracture toughness, and axial compression. Six sets of whole-bone
      samples of human male cadaveric humerus, ulna, and radius (age of donor: 35 to 56
      years) were tested. The results were analyzed for statistical significance by 2
      stage, repeated-measure analysis of variance (ANOVA). The difference between the
      bending strength of the humerus, ulna, and radius was statistically significant (
      P = .001) when compared to one another. However, the fracture toughness and
      compressive strength were observed to be similar for the 3 bones. The knowledge
      of mechanical properties of elbow bones can aid in the design of elbow implants
      and upper limb protection systems, and also allow us to identify criteria for
      injury. Further, knowledge of the mechanical properties of the elbow bones can
      aid in calibrating simulations through finite elements analysis.

PMID- 30229702
TI  - Steadfast Standards or Fluctuating Fancies? Stability and Change in People's Mate
      Criteria Over 27 Months.
AB  - Although research on mate preferences has been built on the assumption that the
      criteria people report at one point in time should predict their future
      partnering behavior, little is known about the temporal stability of people's
      standards. Using survey data collected at four time points from 285 originally
      unmarried individuals, this study examined the rank-order, mean-level, individual
      level and ipsative stability of people's mate criteria over 27 months. Overall,
      reported standards exhibited moderate to high baseline stability, with rank-order
      and ipsative estimates comparable to those reported for personality traits. At
      the same time, mean- and individual-level analyses revealed small, but
      significant, increases in participants' reported criteria over the study, as well
      as significant variability in individual trajectories. Consistent with theory,
      the stability of individuals' standards was moderated by several contextual
      factors, including age, changes in perceived mate value, and significant
      relationship events.

PMID- 30229703
TI  - Penalized multiple inflated values selection method with application to SAFER
      data.
AB  - Expanding on the zero-inflated Poisson model, the multiple-inflated Poisson model
      is applied to analyze count data with multiple inflated values. The existing
      studies on the multiple-inflated Poisson model determined the inflated values by
      inspecting the histogram of count response and fitting the model with different
      combinations of inflated values, which leads to relatively complicated
      computations and may overlook some real inflated points. We address a two-stage
      inflated values selection method, which takes all values of count response as
      potential inflated values and adopts the adaptive lasso regularization on the
      mixing proportion of those values. Numerical studies demonstrate the excellent
      performance both on inflated values selection and parameters estimation.
      Moreover, a specially designed simulation, based on the structure of data from a
      randomized clinical trial of an HIV sexual risk education intervention, performs
      well and ensures our method could be generalized to the real situation. An
      empirical analysis of a clinical trial dataset is used to elucidate the multiple
      inflated Poisson model.

PMID- 30229705
TI  - Commentary on "A Framework for Community and Stakeholder Engagement: Experiences
      From a Multicenter Study in Southern Africa".
AB  - Community and stakeholder engagement (CSE) is increasingly acknowledged as
      foundational to global health research. This commentary builds on the multisite
      framework for CSE described in an eco-health study conducted in Southern Africa.
      We acknowledge the context-specific nature of some of the challenges for CSE and
      draw attention to significant issues and concerns that arose from our studies of
      CSE in the context of multisite HIV prevention trials in South Africa, India, and
      Canada: (a) Pretrial-historically based mistrust, identification of appropriate
      gatekeepers, and considering the breadth of community; (b) Trial implementation
      impact of early trial cessations, appropriate community roles and
      responsibilities, and multifaceted stigma; and (c) Posttrial-supporting and
      sustaining CSE mechanisms independent of particular trials. Many of these
      challenges are exacerbated by widespread disparities in wealth and power between
      trial sponsors and participating communities, further supporting the central
      importance of sound CSE practices and infrastructures to advance ethical
      biomedical and public health research.

PMID- 30229704
TI  - Barriers and enablers to deprescribing in people with a life-limiting disease: A
      systematic review.
AB  - BACKGROUND: Knowing the barriers/enablers to deprescribing in people with a life
      limiting disease is crucial for the development of successful deprescribing
      interventions. These barriers/enablers have been studied, but the available
      evidence has not been summarized in a systematic review. AIM: To identify the
      barriers/enablers to deprescribing of medications in people with a life-limiting
      disease. DESIGN: Systematic review, registered in PROSPERO (CRD42017073693). DATA
      SOURCES: A systematic search of MEDLINE, Embase, Web of Science and CENTRAL was
      conducted and extended with a hand search. Peer-reviewed, primary studies
      reporting on barriers/enablers to deprescribing in the context of explicit life
      limiting disease were included in this review. RESULTS: A total of 1026
      references were checked. Five studies met the criteria and were included in this
      review. Three types of barriers/enablers were found: organizational, professional
      and patient (family)-related barriers/enablers. The most prominent enablers were
      organizational support (e.g. for standardized medication review), involvement of
      multidisciplinary teams in medication review and the perception of the importance
      of coming to a joint decision regarding deprescribing, which highlighted the need
      for interdisciplinary collaboration and involving the patient and his family in
      the decision-making process. The most important barriers were shortages in staff
      and the perceived difficulty or resistance of the nursing home resident's family 
      or the resident himself. Conclusion and implications of key findings: The
      scarcity of findings in the literature highlights the importance of filling this
      gap. Further research should focus on deepening the knowledge on these
      barriers/enablers in order to develop sustainable multifaceted deprescribing
      interventions in palliative care.

PMID- 30229709
TI  - Nutritional status and human milk intake of exclusively breast-fed infants at
      high altitude in La Paz, Bolivia - CORRIGENDUM.

PMID- 30229710
TI  - Beyond not bad or just okay: social predictors of young adults' wellbeing and
      functioning (a TRAILS study).
AB  - BACKGROUND: Various childhood social experiences have been reported to predict
      adult outcomes. However, it is unclear how different social contexts may
      influence each other's effects in the long run. This study examined the joint
      contribution of adolescent family and peer experiences to young adult wellbeing
      and functioning. METHODS: Participants came from the TRacking Adolescents'
      Individual Lives Survey (TRAILS) study (n = 2230). We measured family and peer
      relations at ages 11 and 16 (i.e. family functioning, perceived parenting, peer
      status, peer relationship quality), and functioning as the combination of
      subjective wellbeing, physical and mental health, and socio-academic functioning
      at age 22. Using structural equation modelling, overall functioning was indicated
      by two latent variables for positive and negative functioning. Positive, negative
      and overall functioning at young adulthood were regressed on adolescent family
      experiences, peer experiences and interactions between the two. RESULTS: Family
      experiences during early and mid-adolescence were most predictive for later
      functioning; peer experiences did not independently predict functioning.
      Interactions between family and peer experiences showed that both protective and
      risk factors can have context-dependent effects, being exacerbated or
      overshadowed by negative experiences or buffered by positive experiences in other
      contexts. Overall the effect sizes were modest at best. CONCLUSIONS: Adolescent
      family relations as well as the interplay with peer experiences predict young
      adult functioning. This emphasizes the importance of considering the relative
      effects of one context in relation to the other.

PMID- 30229711
TI  - Trauma-associated anterior cingulate connectivity during reward learning predicts
      affective and anxiety states in young adults.
AB  - BACKGROUND: Trauma exposure is associated with development of depression and
      anxiety; yet, some individuals are resilient to these trauma-associated effects.
      Differentiating mechanisms underlying development of negative affect and
      resilience following trauma is critical for developing effective interventions.
      One pathway through which trauma could exert its effects on negative affect is
      reward-learning networks. In this study, we examined relationships among lifetime
      trauma, reward-learning network function, and emotional states in young adults.
      METHODS: One hundred eleven young adults self-reported trauma and emotional
      states and underwent functional magnetic resonance imaging during a monetary
      reward task. Trauma-associated neural activation and functional connectivity were
      analyzed during reward prediction error (RPE). Relationships between trauma
      associated neural functioning and affective and anxiety symptoms were examined.
      RESULTS: Number of traumatic events was associated with greater ventral anterior
      cingulate cortex (vACC) activation, and lower vACC connectivity with the right
      insula, frontopolar, inferior parietal, and temporoparietal regions, during RPE.
      Lower trauma-associated vACC connectivity with frontoparietal regions implicated
      in regulatory and decision-making processes was associated with heightened
      affective and anxiety symptoms; lower vACC connectivity with insular regions
      implicated in interoception was associated with lower affective and anxiety
      symptoms. CONCLUSIONS: In a young adult sample, two pathways linked the impact of
      trauma on reward-learning networks with higher v. lower negative affective and
      anxiety symptoms. The disconnection between vACC and regions implicated in
      decision-making and self-referential processes may reflect aberrant regulatory
      but appropriate self-focused mechanisms, respectively, conferring risk for v.
      resilience against negative affective and anxiety symptoms.

PMID- 30229712
TI  - A single dose of beetroot juice improves endothelial function but not tissue
      oxygenation in pregnant women: a randomised clinical trial.
AB  - Beetroot juice (BJ) consumption has been associated with improved cardiovascular
      health owing to an increase in NO bioconversion. This study evaluates the effect
      of BJ consumption on macrovascular endothelial function (flow-mediated dilation
      (FMD)) and muscle oxygen saturation (StO2) parameters in pregnant women within a
      randomised, crossover, double-blind design in which twelve pregnant women
      consumed a single dose (140 ml) of BJ or placebo (PLA). Urinary nitrate was
      assessed before (T0) and 150 min after BJ/PLA consumption. FMD was used to
      evaluate macrovascular endothelial function, and near-IR spectroscopy was used to
      evaluate muscle StO2 parameters during the occlusion and reperfusion phases,
      which were taken at baseline (PRE) and 120 and 140 min after BJ/PLA consumption,
      respectively. A significant increase in urinary nitrate was observed at 150 min
      after BJ consumption when compared with T0 (BJ: 0.20 (sd 0.13) v. T0: 0.02 (sd
      0.00), P=0.000) and PLA intervention (PLA: 0.02 (sd 0.00), P=0.001). FMD improved
      after BJ consumption when compared with PRE (BJ: 11.00 (sd 1.67) v. PRE: 5.53 (sd
      1.17), P=0.000) and PLA (5.34 (sd 1.31), P=0.000). No significant difference
      between PLA and PRE in FMD (P=1.000) was observed. In StO2 parameters, a
      difference was not observed after BJ consumption compared with PRE and PLA
      intervention. The data demonstrate that a single dose of 140 ml of BJ consumption
      improves macrovascular endothelial function, but not StO2 parameters.

PMID- 30229713
TI  - Aberrant myelination of the cingulum and Schneiderian delusions in schizophrenia:
      a 7T magnetization transfer study.
AB  - BACKGROUND: The structural integrity of the anterior cingulum has been repeatedly
      observed to be abnormal in patients with schizophrenia. More recently, aberrant
      myelination of frontal fasciculi, especially, cingulum has been proposed to
      underlie delayed corollary discharges that can affect sense of agency and
      contribute to delusions of control (Schneiderian delusions). Using the
      magnetization transfer phenomenon at an ultra-high field 7T MRI, we investigated
      the putative myelin content of cingulum bundle in patients with schizophrenia.
      METHODS: Seventeen clinically stable patients with schizophrenia and 20 controls
      were recruited for this 7T MRI study. We used a region-of-interest method and
      extracted magnetization transfer ratio (MTR) from left and right dorsal cingulum
      bundles and estimated patients v. controls differences. We also related the
      cingulum MTR values to the severity of Schneiderian delusions. RESULTS: Patients
      had a significant reduction in the MTR, indicating reduced myelin content, in the
      cingulum bundle (right cingulum Hedges' g = 0.91; left cingulum g = 0.03). The
      reduced MTR of left cingulum was associated with higher severity of Schneiderian
      delusions (tau = -0.45, p = 0.026) but no such relationship was seen for the
      right cingulum MTR (tau = -0.136, p = 0.50) among patients. The association
      between the left cingulum MTR and Schneiderian delusions was not explained by the
      presence of other delusions, hallucinations, disorganization or negative
      symptoms. CONCLUSIONS: Dysmyelination of the cingulum bundle is seen in a
      subgroup of patients with schizophrenia and may be involved in the mechanism of
      Schneiderian delusions.

PMID- 30229714
TI  - Diarrhoeagenic Escherichia coli and Escherichia albertii in Brazil: pathotypes
      and serotypes over a 6-year period of surveillance.
AB  - Diarrhoeagenic Escherichia coli (DEC) is a leading cause of infectious diarrhoea
      worldwide. In recent years, Escherichia albertii has also been implicated as a
      cause of human enteric diseases. This study describes the occurrence of E. coli
      pathotypes and serotypes associated with enteric illness and haemolytic uremic
      syndrome (HUS) isolated in Brazil from 2011 to 2016. Pathotypes isolated included
      enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC),
      enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC) and Shiga toxin
      producing E. coli (STEC). PCR of stool enrichments for DEC pathotypes was
      employed, and E. albertii was also sought. O:H serotyping was performed on all
      DEC isolates. A total of 683 DEC and 10 E. albertii strains were isolated from
      5047 clinical samples. The frequencies of DEC pathotypes were 52.6% (359/683) for
      EPEC, 32.5% for EAEC, 6.3% for ETEC, 4.4% for EIEC and 4.2% for STEC. DEC strains
      occurred in patients from 3 months to 96 years old, but EPEC, EAEC and STEC were
      most prevalent among children. Both typical and atypical isolates of EPEC and
      EAEC were recovered and presented great serotype heterogeneity. HUS cases were
      only associated with STEC serotype O157:H7. Two E. albertii isolates belonged to
      serogroup O113 and one had the stx2f gene. The higher prevalence of atypical EPEC
      in relation to EAEC in community-acquired diarrhoea in Brazil suggests a shift in
      the trend of DEC pathotypes circulation as previously EAEC predominated. This is
      the first report of E. albertii isolation from active surveillance. These results
      highlight the need of continuing DEC and E. albertii surveillance, as a mean to
      detect changes in the pattern of pathotypes and serotypes circulation and provide
      useful information for intervention and control strategies.

PMID- 30229715
TI  - Hippocampal-subregion functional alterations associated with antidepressant
      effects and cognitive impairments of electroconvulsive therapy.
AB  - BACKGROUND: Electroconvulsive therapy (ECT), an effective antidepressive
      treatment, is frequently accompanied by cognitive impairment (predominantly
      memory), usually transient and self-limited. The hippocampus is a key region
      involved in memory and emotion processing, and in particular, the anterior
      posterior hippocampal subregions has been shown to be associated with emotion and
      memory. However, less is known about the relationship between hippocampal
      subregion alterations following ECT and antidepressant effects or cognitive
      impairments. METHODS: Resting-state functional connectivity (RSFC) based on the
      seeds of hippocampal subregions were investigated in 45 pre- and post-ECT
      depressed patients. Structural connectivity between hippocampal subregions and
      corresponding functionally abnormal regions was also conducted using
      probabilistic tractography. Antidepressant effects and cognitive impairments were
      measured by the Hamilton Depressive Rating Scale (HDRS) and the Category Verbal
      Fluency Test (CVFT), respectively. Their relationships with hippocampal
      subregions alterations were examined. RESULTS: After ECT, patients showed
      increased RSFC in the hippocampal emotional subregion (HIPe) with the left middle
      occipital gyrus (LMOG) and right medial temporal gyrus (RMTG). Decreased HDRS was
      associated with increased HIPe-RMTG RSFC (r = -0.316, p = 0.035) significantly
      and increased HIPe-LMOG RSFC at trend level (r = -0.283, p = 0.060). In contrast,
      the hippocampal cognitive subregion showed decreased RSFC with the bilateral
      angular gyrus, and was correlated with decreased CVFT (r = 0.418, p = 0.015 for
      left; r = 0.356, p = 0.042 for right). No significant changes were found in
      structural connectivity. CONCLUSION: The hippocampal-subregions functional
      alterations may be specially associated with the antidepressant and cognitive
      effects of ECT.

PMID- 30229716
TI  - Letter to editor in response to imported leishmaniasis in Sweden 1993-2016.

PMID- 30229717
TI  - Estimating the probability of freedom from bovine brucellosis in the Galapagos
      Islands.
AB  - Bovine brucellosis is a worldwide zoonotic disease that still burdens several
      countries in the Mediterranean, Asia, Africa and Latin America. Although the
      disease is present in Ecuador, the Galapagos Islands seem to be free from the
      disease based on a survey conducted in 1997 where all tested animals showed
      negative results. This study aimed at estimating the probability of freedom from
      brucellosis in this Ecuadorian province in 2014. A survey was implemented on the
      three main cattle-producing islands of the province: Santa Cruz, Isabela and San
      Cristobal. Thirty-three cattle farms and 410 cattle were tested for brucellosis
      using the Rose Bengal test and indirect ELISA. All animals showed negative
      results for both tests. Probability of freedom was estimated at 98%, 91% and 88%
      for Santa Cruz, Isabela and San Cristobal, respectively, considering a herd-level
      design seroprevalence of 20% and animal-level design seroprevalence of 15%, and
      assuming a perfect specificity of the survey. The negative results found in 1997
      and present surveys suggest that the Galapagos Islands are free from bovine
      brucellosis.

PMID- 30229718
TI  - What leads to innovation in mental healthcare? Reflections on clinical expertise
      in a bureaucratic age.
AB  - SummaryThis paper considers a witness seminar in which healthcare professionals
      discussed working on an acute admissions ward run along therapeutic community
      lines from the 1960s to the 1980s. Participants remarked that older styles of
      working are 'unimaginable' today. This paper discusses why. Literature from the
      humanities and social sciences suggest healthcare is reactive, reflecting wider
      cultural changes, including a preference for a more bureaucratic, standardised,
      explicit style of reasoning and a high valuation of personal autonomy. Such a
      reflection prompts questions about the nature of professional expertise, the role
      of evidence and the importance of the humanities and social sciences.Declaration
      of interestNone.

PMID- 30229719
TI  - An evaluation of sleep disturbance on in-patient psychiatric units in the UK.
AB  - : Aims and methodSleep disturbance is common on in-patient psychiatry wards. This
      study explored subjective and objective patterns of sleep disturbance and
      contributory environmental factors. Participants were recruited from mental
      health acute admission wards and had a range of subjective and objective
      assessments of sleep. Light intensity and noise levels were measured to
      characterise potential environmental causes for poor sleep. RESULTS: We recruited
      20 patients; 15% were high risk for obstructive sleep apnoea. Nineteen
      participants reported poor sleep quality on the Pittsburgh Sleep Quality Index,
      and 90% had significant sleep fragmentation with objective measures. Inside light
      levels were low (day <200 lux and night <10 lux). Night sound levels were 40-90
      db.Clinical implicationsSleep disturbance was highly prevalent. Increased
      awareness of sleep disorders is needed. Modifiable environmental factors on the
      ward were implicated, therefore increased awareness and a change of approach to
      sleep disturbance in in-patient psychiatry is recommended.Declaration of
      interestNone.

PMID- 30229720
TI  - Dear BJPsych Bulletin....
AB  - SummaryThe editor thanks the outgoing Correspondence Editor Greg Shields and
      welcomes Dr William Badenhorst as his successor. He reflects upon his own
      inadequacy as a letter writer in the hope it encourages others to be
      better.Declaration of interestNone.

PMID- 30229721
TI  - Job vacancy at the European Centre for Disease Prevention and Control.

PMID- 30229722
TI  - Letter to the editor: Occurrence of modified measles during outbreak in Taiwan in
      2018.

PMID- 30229723
TI  - Usability of the international HAVNet hepatitis A virus database for geographical
      annotation, backtracing and outbreak detection.
AB  - BackgroundHAVNet is an international laboratory network sharing sequences and
      corresponding metadata on hepatitis A virus in an online database. Aim: We give
      an overview of the epidemiological and genetic data and assess the usability of
      the present dataset for geographical annotation, backtracing and outbreak
      detection. Methods: A descriptive analysis was performed on the timeliness,
      completeness, epidemiological data and geographic coverage of the dataset. Length
      and genomic region of the sequences were reviewed as well as the numerical and
      geographical distribution of the genotypes. The geographical signal in the
      sequences was assessed based on a short common nt stretch using a 100% identity
      analysis. Results: The 9,211 reports were heterogeneous for completeness and
      timeliness, and for length and genomic region of the sequences. Some parts of the
      world were not represented by the sequences. Geographical differences in
      prevalence of HAV genotypes described previously could be confirmed with this
      dataset and for a third (1,075/3,124) of the included sequences, 100% identity of
      the short common sequence coincided with an identical country of origin.
      Conclusion: Analysis of a subset of short, shared sequences indicates that a
      geographical annotation on the level of individual countries is possible with the
      HAVNet data. If the current incompleteness and heterogeneity of the data can be
      improved on, HAVNet could become very useful as a worldwide reference set for
      geographical annotation and for backtracing and outbreak detection.

PMID- 30229724
TI  - Molecular diversity and biennial circulation of enterovirus D68: a systematic
      screening study in Lyon, France, 2010 to 2016.
AB  - BackgroundUnderstanding enterovirus D68 (EV-D68) circulation patterns as well as
      risk factors for severe respiratory and neurological illness is important for
      developing preventive strategies. Methods: Between 2010 and 2016, 11,132
      respiratory specimens from hospitalised patients in Lyon, France, were screened
      for EV-D68 by PCR. Phylogenetic relationships of the viral-protein-1 sequences
      were reconstructed using maximum-likelihood and Bayesian-Markov-Chain-Monte-Carlo
      approaches. Results: Overall, 171 infections with a biennial pattern were
      detected, including seven, one, 55, none, 42, one and 65 cases annually during
      2010-16. Children (< 16 years-old; n = 150) were mostly affected and 71% (n =
      121) of the total patients were under 5 years-old. In 146 patients with medical
      reviews, 73% (n = 107) presented with acute respiratory distress. Among
      paediatric patients with medical reviews (n = 133), 55% (n=73) had an
      asthma/wheezing history, while among adults (n = 13), 11 had underlying diseases.
      In total, 45 patients had severe infections and 28 patients needed intensive care
      unit stays. No acute flaccid myelitis (AFM) was detected. We found genotypes A,
      B1, B2 B3 and D circulating, and no associations between these and clinical
      presentations. During the study, new genotypes continuously emerged, being
      replaced over time. We estimated that ancestors of currently circulating
      genotypes emerged in the late-1990s to 2010. Rises of the EV-D68 effective
      population size in Lyon coincided with infection upsurges. Phylogenetic analyses
      showed ongoing diversification of EV-D68 worldwide, coinciding with more
      infections in recent years and increases of reported AFM paediatric cases.
      Conclusions: Reinforcement of diagnostic capacities and clinical-based
      surveillance of EV-D68 infections is needed in Europe to assess the EV-D68
      burden.

PMID- 30229726
TI  - Editorial.

PMID- 30229725
TI  - National outbreak of Pseudomonas aeruginosa associated with an aftercare solution
      following piercings, July to September 2016, England.
AB  - We report a national Pseudomonas aeruginosa outbreak from a common source
      following piercings between July and September 2016 in England. The multi-agency
      outbreak investigation included active case finding, microbiological testing of
      environmental samples and case specimens including Variable Number Tandem Repeat
      (VNTR) typing and a retrospective cohort study. Overall, 162 outbreak cases (29
      confirmed, 14 probable and 119 possible) and 14 non-outbreak cases were
      identified; all confirmed cases had ear piercings (93% cartilage). Outbreak cases
      were predominantly female (95%) and had a median age of 18 years (interquartile
      range: 13-56 years). Nineteen outbreak cases required surgery under general
      anaesthetic The same outbreak VNTR type (11,3,5,3,3,3,6,4,7) was isolated from
      bottles of an aftercare solution from a single manufacturer and in specimens from
      confirmed cases who attended eight different piercing studios supplied with this
      product. In the cohort study, use of aftercare solution was associated with
      becoming a case (aOR: 4.60, 95% confidence interval: 1.65-12.90). Environmental,
      microbiological and epidemiological investigations confirmed that contamination
      during production of aftercare solution was the source of this national outbreak;
      highlighting challenges in the regulation of a cosmetic products used in the
      piercing industry and that guidance on piercing aftercare may need to be
      reviewed.

PMID- 30229727
TI  - Nasopharyngeal colonisation and antimicrobial resistance of Streptococcus
      pneumoniae in Hong Kong children younger than 2 years.

PMID- 30229728
TI  - Influenza surveillance and vaccination in Hong Kong children.

PMID- 30229729
TI  - Influenza-like illness and viral aetiology in Hong Kong children.

PMID- 30229730
TI  - Surveillance of human- and swine-origin influenza in Hong Kong children.

PMID- 30229731
TI  - Estimation of excess mortality and hospitalisation associated with the 2009
      pandemic influenza.

PMID- 30229733
TI  - Real-time forecasting of infectious disease epidemics.

PMID- 30229732
TI  - Development of adaptable pandemic simulation models.

PMID- 30229734
TI  - Decision-making process of families about human papillomavirus vaccination of
      adolescent daughters: a qualitative study of Hong Kong Chinese families.

PMID- 30229735
TI  - Mothers' preference and willingness to pay for human papillomavirus vaccination
      for their daughters: a discrete choice experiment.

PMID- 30229737
TI  - Development of an automated 16S rRNA gene sequence database, 16SpathDB, for
      identification of medically important bacteria.

PMID- 30229736
TI  - Multilevel antimicrobial disinfectant coating in reducing the viability of
      multidrug-resistant organisms in hospital environment.

PMID- 30229738
TI  - Sonodynamic bactericidal activity of curcumin against foodborne bacteria.

PMID- 30229739
TI  - Indirubin-3'-oxime as an antiviral and immunomodulatory agent in treatment of
      severe human influenza virus infection.

PMID- 30229741
TI  - Hierarchical metal/polymer metamaterials of tunable negative Poisson's ratio
      fabricated by initiator-integrated 3D printing (i3DP).
AB  - Metamaterials with artificially designed architectures can achieve unique and
      even unprecedented physical properties, which show promising applications in
      actuators, amplifiers and micromechanical controls. An initiator-integrated 3D
      printing technology (i3DP) was applied in this study to create scalable,
      metal/polymer meta-mechanical materials, which can gradually achieve negative
      Poisson's ratio, high strength and ultralow density, as well as high compressive
      and super-elastic behavior. The i3DP was enabled by integrating an atomic
      transfer radical polymerization (ATRP) initiator with UV-curable resin, followed
      by polyelectrolyte brushes (PMETAC) grafting via surface-initiated ATRP and
      thereafter electroless plating to form metal coatings. Compared with polymer
      structures, the compressive stress of metal-polymer structure can be doubled when
      deposited with a 190 nm copper layer. The hollow metallic materials possess a
      tunable Poisson's ratio, and the highest average recoverability, which can
      recover nearly completely to their original shape after over 30% compression.
      Overall, this i3DP approach provides meta-structures with substantial benefits
      from the hierarchical design and fabrication flexibility.

PMID- 30229742
TI  - Controlling electron flow in anisotropic Dirac materials heterojunctions: a super
      diverging lens.
AB  - Ballistic heterojunctions of Dirac materials offer the opportunity of exploring
      optics-like phenomena in electronic systems. In this paper, a new perfect lens
      through special positive refraction is predicted with omnidirectional Klein
      tunneling of massless Dirac fermions. The novel optics component called a super
      diverging lens (SDL) is the counterpart of a Veselago lens (VL). The use of SDL
      and VL creates a device that simulates the ocular vision. This atypical
      refraction is due to electrons obeying different Snell's laws of pseudo-spin and
      group velocity in heterojunctions with elliptical Dirac cones. These findings
      pave the way for an electron elliptical Dirac optics and open up new
      possibilities for the guiding of electrons.

PMID- 30229740
TI  - Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using
      direct 100Mo(p,2n) reaction.
AB  - Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq
      amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets
      at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range
      was chosen since it is easily achievable by many conventional medical cyclotrons
      already available in the nuclear medicine departments of hospitals. The main
      motivation for such a study is in the framework of the research activities at the
      international level that have been conducted over the last few years to develop
      alternative production routes for the most widespread radioisotope used in
      medical imaging. The analysis of technetium isotopes and isomeric states (9xTc)
      present in the pertechnetate saline Na99mTcO4 solutions, obtained after the
      extraction/purification procedure, reveals radionuclidic purity levels basically
      in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018
      Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc
      contaminant nuclides on the final image quality is thoroughly evaluated,
      analyzing the emitted high-energy gamma rays and their influence on the image
      quality. The spatial resolution of images from cyclotron-produced 99mTc acquired
      with a mini-gamma camera was determined and compared with that obtained using
      technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect
      of the increased image background contribution due to Compton-scattered higher
      energy gamma rays (E gamma   >  200 keV), which could cause image-contrast
      deterioration, was also studied. It is concluded that, due to the high
      radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction
      at a proton beam energy in the range 15.7-19.4 MeV, the resulting image
      properties are well comparable with those from the generator-eluted 99mTc.

PMID- 30229743
TI  - Interplay between nematic fluctuation and superconductivity in a two-orbital
      Hubbard model: a quantum Monte Carlo study.
AB  - To understand the interplay between nematic fluctuation and superconductivity in
      iron-based superconductors, we performed a systematic study of the realistic two
      orbital Hubbard model at intermedium correlation regimes by using the constrained
      path quantum Monte Carlo method. Our numerical results showed that the on-site
      nematic interaction induces a strong enhancement of nematic fluctuations at
      various momentums, especially at ([Formula: see text]). Simultaneously, it was
      found that the on-site nematic interaction suppresses the [Formula: see text]
      antiferromagnetic order and long-range electron pairing correlations for dominant
      pairing channels. Our findings suggest that on-site nematic fluctuation seems to
      compete with superconductivity in iron-based superconductors.

PMID- 30229744
TI  - Efficient ion-slicing of InP thin film for Si-based hetero-integration.
AB  - Integration of high quality single crystalline InP thin film on Si substrate has
      potential applications in Si-based photonics and high-speed electronics. In this
      work, the exfoliation of a 634 nm crystalline InP layer from the bulk substrate
      was achieved by sequential implantation of He ions and H ions at room
      temperature. It was found that the sequence of He and H ion implantations has a
      decisive influence on the InP surface blistering and exfoliation, which only
      occur in the InP pre-implanted with He ions. The exfoliation efficiency first
      increases and then decreases as a function of H ion implantation fluence. A
      kinetics analysis of the thermally activated blistering process suggests that the
      sequential implantation of He and H ions can reduce the InP thin film splitting
      thermal budget dramatically. Finally, a high quality 2 inch InP-on-Si(100) hetero
      integration wafer was fabricated by He and H ion sequential implantation at room
      temperature in combination with direct wafer bonding.

PMID- 30229745
TI  - Robust simultaneous myoelectric control of multiple degrees of freedom in wrist
      hand prostheses by real-time neuromusculoskeletal modeling.
AB  - OBJECTIVE: Robotic prosthetic limbs promise to replace mechanical function of
      lost biological extremities and restore amputees' capacity of moving and
      interacting with the environment. Despite recent advances in biocompatible
      electrodes, surgical procedures, and mechatronics, the impact of current
      solutions is hampered by the lack of intuitive and robust man-machine interfaces.
      APPROACH: This work presents a biomimetic interface that synthetizes the
      musculoskeletal function of an individual's phantom limb as controlled by neural
      surrogates, i.e. electromyography-derived neural activations. With respect to
      current approaches based on machine learning, our method employs explicit
      representations of the musculoskeletal system to reduce the space of feasible
      solutions in the translation of electromyograms into prosthesis control commands.
      Electromyograms are mapped onto mechanical forces that belong to a subspace
      contained within the broader operational space of an individual's musculoskeletal
      system. MAIN RESULTS: Our results show that this constraint makes the approach
      applicable to real-world scenarios and robust to movement artefacts. This stems
      from the fact that any control command must always exist within the
      musculoskeletal model operational space and be therefore physiologically
      plausible. The approach was effective both on intact-limbed individuals and a
      transradial amputee displaying robust online control of multi-functional
      prostheses across a large repertoire of challenging tasks. SIGNIFICANCE: The
      development and translation of man-machine interfaces that account for an
      individual's neuromusculoskeletal system creates unprecedented opportunities to
      understand how disrupted neuro-mechanical processes can be restored or replaced
      via biomimetic wearable assistive technologies.

PMID- 30229746
TI  - One-particle Green's function of interacting two electrons using analytic
      solutions for a three-body problem: comparison with exact Kohn-Sham system.
AB  - For a three-electron system with finite-strength interactions confined to a one
      dimensional harmonic trap, we solve the Schrodinger equation analytically to
      obtain the exact solutions, from which we construct explicitly the simultaneous
      eigenstates of the energy and total spin for the first time. The solutions for
      the three-electron system allow us to derive analytic expressions for the exact
      one-particle Green's function (GF) for the corresponding two-electron system. We
      calculate the GF in frequency domain to examine systematically its behavior
      depending on the electronic interactions. We also compare the pole structure of
      non-interacting GF using the exact Kohn-Sham (KS) potential with that of the
      exact GF to find that the discrepancy of the energy gap between the KS system and
      the original system is larger for a stronger interaction. We perform numerical
      examination on the behavior of GFs in real space to demonstrate that the exact
      and KS GFs can have shapes quite different from each other. Our simple model will
      help to understand generic characteristics of interacting GFs.

PMID- 30229747
TI  - Relieving phantom limb pain with multimodal sensory-motor training.
AB  - OBJECTIVE: The causes for the disabling condition of phantom limb pain (PLP),
      affecting 85% of amputees, are so far unknown, with few effective treatments
      available. Sensory feedback based strategies to normalize the motor commands to
      control the phantom limb offer important targets for new effective treatments as
      the correlation between phantom limb motor control and sensory feedback from the
      motor intention has been identified as a possible mechanism for PLP development.
      APPROACH: Ten upper-limb amputees, suffering from chronic PLP, underwent 16 days
      of intensive training on phantom-limb movement control. Visual and tactile
      feedback, driven by muscular activity at the stump, was provided with the aim of
      reducing PLP intensity. MAIN RESULTS: A 32.1% reduction of PLP intensity was
      obtained at the follow-up (6 weeks after the end of the training, with an initial
      21.6% reduction immediately at the end of the training) reaching clinical
      effectiveness for chronic pain reduction. Multimodal sensory-motor training on
      phantom-limb movements with visual and tactile feedback is a new method for PLP
      reduction. SIGNIFICANCE: The study results revealed a substantial reduction in
      phantom limb pain intensity, obtained with a new training protocol focused on
      improving phantom limb motor output using visual and tactile feedback from the
      stump muscular activity executed to move the phantom limb.

PMID- 30229748
TI  - A gold nanoparticle system for the enhancement of radiotherapy and simultaneous
      monitoring of reactive-oxygen-species formation.
AB  - Gold nanoparticles (AuNPs) are known to sensitize cancer cells to radiation
      therapy (RT) by increasing the deposition of ionizing energy in their immediate
      vicinity. However, this process of dose enhancement is challenging to monitor
      because it is heterogeneous at the sub-cellular scale. Furthermore, radiation
      damage is primarily mediated by reactive oxygen species (ROS) that are produced
      following water radiolysis. Here, radiation-responsive PEGylated gold
      nanoparticles (RPAuNPs) were synthesized for the enhanced generation and
      concurrent detection of ROS in cancer cells and tumors. PEGylated gold particles
      (20 nm diameter) were functionalized with dihydrorhodamine 123 (DHR-123), a known
      ROS sensor, to monitor ROS generation in their immediate vicinity. These NPs were
      able to effectively radiosensitize cells, as measured by increased cell apoptosis
      following RT. Furthermore, the fluorescence of these RPAuNPs was 7-fold higher
      after 6 Gy RT due to the local production of ROS near the surface of the NP.
      Finally, multispectral fluorescence imaging was used to monitor NP-induced ROS in
      vivo, following conformal RT, in a xenograft model of breast cancer. This
      theranostic NP system provides a novel approach for monitoring the nanoscale
      enhancement of RT by high-Z metal NPs.

PMID- 30229749
TI  - A novel tissue-engineered 3D tumor model for anti-cancer drug discovery.
AB  - Cancer biology and drug discovery are heavily dependent on conventional 2D cell
      culture systems. However, a 2D culture is significantly limited by its ability to
      reflect 'true biology' of tumor in vivo. Three-dimensional (3D) in vitro cell
      culture models have been introduced to aid cancer drug discovery by better
      modeling the tumor microenvironment. Here, decellularized lung scaffolds cultured
      with MCF-7 cancer cells were bioengineered as a platform to study tumor
      development and anti-cancer drug evaluation. Excellent cell compatibility of
      decellularized lung scaffolds promoted cell growth and proliferation.
      Multicellular tumor cell spheroids (tumoriods) were formed and enlarged
      exclusively in decellularized lung scaffolds over time. The expression of breast
      cancer biomarkers (BRCA1 and HER2) in MCF-7 cells significantly increased in the
      lung matrix compared to those cultured in 2D systems. Insufficient oxygen and
      nutrient diffusion into the internal surface of lung scaffolds resulted in
      intracellular hypoxia, quantified by a significant upregulation of HIF-1alpha
      protein expression compared to that of cell monolayers. Higher survival rates
      after exposure to 5-FU were observed in lung scaffolds (52.04%) compared to that
      in 2D systems (18.39%) on day 3 of culture. Overall, this new breast tumor system
      provides a promising platform to study breast cancer progression and develop new
      targeted therapeutic strategies.

PMID- 30229750
TI  - Magnetic structure and field-dependent magnetic phase diagram of Ni2In-type
      PrCuSi.
AB  - The magnetic structure of the ternary equiatomic intermetallic compound PrCuSi is
      investigated using neutron powder diffraction experiments in 0 T as well as in
      external magnetic fields up to 2 T. The PrCuSi compound crystallizes in the
      hexagonal Ni2In-type structure, in the space group P63/mmc. In this structure,
      cationic ordering of Cu and Si takes place. The antiferromagnetic phase
      transition in the Pr sublattice takes place at [Formula: see text] K in 0 T.
      Under an external magnetic field of 2 T, a field-induced ferromagnetic phase is
      observed. Magnetoelastic coupling is evidenced by an increase in the unit cell
      volume. Clear signatures of a mixed antiferromagnetic and ferromagnetic phase in
      weak, intermediate fields, 0.4-0.8 T, are obtained from the present study. Using
      the present set of experimental data, we construct the H  -  T phase diagram of
      PrCuSi.

PMID- 30229751
TI  - Efficacy and Safety of High-Dose Controlled-Release Oxycodone in the Treatment of
      Moderate to Severe Pain in Patients with Advanced Cancer: A Retrospective Study.
AB  - BACKGROUND Opioid analgesics are used to relieve pain in patients with cancer and
      can improve their quality of life. This study aimed to investigate the efficacy
      and tolerability of high-dose (>150 mg/day) controlled-release oxycodone for the
      control of pain in patients with advanced solid malignant tumors. MATERIAL AND
      METHODS A retrospective clinical study was undertaken to include patients with
      advanced cancer treated at the Zhejiang Cancer Hospital who had treatment that
      included high-dose controlled-release oxycodone. The subjective numeric rating
      scale (NRS) for assessment of pain intensity (scores between 0-10) was used in
      all cases. RESULTS The study included 131 patients with advanced solid tumors
      with moderate to severe cancer pain. The mean NRS score before commencing high
      dose controlled-release oxycodone was 7.10. The effective rate of relief pain was
      achieved in 90.1% (118/131) of patients, with an average effective dose of
      controlled-release oxycodone of 177.18+/-11.71 mg/day, resulting in a mean NRS of
      2.15. There were 51 patients who achieved pain relief with mean treatment
      duration of 49.98+/-11.71 days. Combination therapy was required in 79 patients.
      Additional drugs included gabapentin (43 patients), pregabalin (10 patients) and
      non-steroidal anti-inflammatory drugs (NSAIDS) (26 patients). The main side
      effects of high-dose controlled-release oxycodone included constipation, nausea,
      vomiting, dysuria, dizziness, and drowsiness, but no patients discontinued
      treatment because of these. CONCLUSIONS This study showed that high-dose
      controlled-release oxycodone could effectively relieve moderate to severe cancer
      pain, without side effects that were severe enough to result in discontinuation
      of treatment.

PMID- 30229752
TI  - Erratum: Optimizing Performance: Emergency Department Sepsis Champions Past,
      Present, and Future: Erratum.
AB  - [This corrects the article DOI: 10.1097/pq9.0000000000000068.].

PMID- 30229753
TI  - Erratum: Introduction: Proceedings of the Improved Pediatric Sepsis Outcomes
      Colloquium-Dallas TX, December 2017: Erratum.
AB  - [This corrects the article DOI: 10.1097/pq9.0000000000000075.].

PMID- 30229754
TI  - Nontrivial topology and topological phase transition in two-dimensional monolayer
      Tl.
AB  - Topological insulating material with dissipationless edge states is a rising star
      in spintronics. While most two-dimensional (2D) topological insulators belong to
      group-IV or -V elements in a honeycomb lattice, herein, we propose a new
      topological phase in the 2D hexagonal group-III crystal, h-Tl, based on a tight
      binding model and density-functional theory calculation. Analysis of band
      dispersion reveals a Dirac nodal-ring near the Fermi level, which is attributed
      to px,y/pz band crossing. Upon inclusion of spin-orbit coupling (SOC), h-Tl turns
      into a quantum spin Hall insulator under 21% biaxial strain, confirmed by
      integrating spin Berry curvature in the Brillouin zone and spin-polarized edge
      states. A prominent feature of its electronic properties is that the effect of
      SOC plays two essential roles of both topological gap opening and band inversion
      between px,y/pz orbitals, which is the first observed phenomenon in 2D materials.
      This study extends the scope of 2D elemental topological insulators and presents
      a platform to design new 2D topotronics materials.

PMID- 30229755
TI  - EPR sensing of metal and organic cations using a novel spin-labelled dibenzo-24
      crown-8-ether.
AB  - The synthesis of novel dibenzo-24-crown ether substituted nitroxides and their
      use as spin probes for the detection of cation guests by EPR are reported.
      Formation of a host-guest complex between the proposed spin probes and several
      cations, both organic and inorganic, was evidenced by a significant change in the
      value of the benzylic and nitrogen EPR hyperfine splittings upon complexation.
      This favorable feature provided a reliable EPR sensor that is able to selectively
      distinguish different cationic guests.

PMID- 30229756
TI  - How do the hydrocarbon chain length and hydroxyl group position influence the
      solute dynamics in alcohol-based deep eutectic solvents?
AB  - Deep eutectic solvents (DESs) have received considerable attention in recent
      years as new sustainable green media and some of their interesting properties
      have stimulated investigations on the microscopic solution structure, solute
      solvent interactions and solute/solvation dynamics in these media. Even though
      the alcohol-based DESs, due to their low viscosity, serve as useful media in
      various applications, little is known about the structure and dynamics of these
      solvents. In order to obtain insight into the microscopic structure and
      interactions operating in these media, we have studied the rotational and
      translational diffusion dynamics of some carefully chosen molecular systems (both
      dipolar and nonpolar) using time-resolved fluorescence anisotropy and
      fluorescence correlation spectroscopy techniques in a series of choline
      chloride/alcohol based DESs differing in hydrocarbon chain length and positioning
      of the hydroxyl group on the hydrogen bond donor. The results reveal an increase
      of both spatial and dynamic heterogeneity upon an increase in chain length of one
      of the components of these solvents. No significant variation of heterogeneity,
      however, could be observed with the change in the hydroxyl group position. The
      analysis of the experimental results indicates that solute-solvent hydrogen
      bonding interaction plays a dominant role in determining both rotational and
      translational diffusion dynamics of AP in these DESs.

PMID- 30229758
TI  - Heat transport in pristine and polycrystalline single-layer hexagonal boron
      nitride.
AB  - We use a phase field crystal model to generate large-scale bicrystalline and
      polycrystalline single-layer hexagonal boron nitride (h-BN) samples and employ
      molecular dynamics (MD) simulations with the Tersoff many-body potential to study
      their heat transport properties. The Kapitza thermal resistance across individual
      h-BN grain boundaries is calculated using the inhomogeneous nonequilibrium MD
      method. The resistance displays strong dependence on the tilt angle, the line
      tension and the defect density of the grain boundaries. We also calculate the
      thermal conductivity of pristine h-BN and polycrystalline h-BN with different
      grain sizes using an efficient homogeneous nonequilibrium MD method. The in-plane
      and the out-of-plane (flexural) phonons exhibit different grain size scalings of
      the thermal conductivity in polycrystalline h-BN and the extracted Kapitza
      conductance is close to that of large-tilt-angle grain boundaries in bicrystals.

PMID- 30229757
TI  - Group-VIII transition metal boride as promising hydrogen evolution reaction
      catalysts.
AB  - Searching for alternative catalysts for hydrogen evolution reaction (HER) under
      acidic conditions has been a major challenge in chemistry. Herein, we demonstrate
      that it is now feasible to identify unprecedented transition metal boride phases
      that are both stable and active for HER via stochastic global potential energy
      surface scanning. We show that B alloying alters the most stable crystal phase
      from face-centered (fcc) to hexagonal close packing (hcp) for both Pd and Rh. In
      particular, Pd2B, the thermodynamically most stable Pd boride with the highest B
      content, is predicted to exhibit an ultra-high intrinsic HER activity, ~2 orders
      of magnitude higher than that of Pt nanoparticles at 0 V vs. NHE. The group VIII
      transition metal boride thus represents a promising HER catalyst to replace
      conventional Pt catalysts.

PMID- 30229759
TI  - Spin-orbit coupling induced spin polarized valley states in SrRuO3/BiIrO3
      heterostructures.
AB  - The electronic properties of SrRuO3/BiIrO3 superlattices are investigated by
      first-principles calculations with spin-orbit coupling. The results show that the
      strength of hybridization near the Fermi level is dependent on the distance
      between the closest transition metal Ru and Ir atoms. We find that both spin and
      valley polarizations in bilayered BiIrO3 are achieved in Bi-terminated models.
      Furthermore, different stacking patterns can modulate the magnitude and sign of
      valley polarization and switch the p- or n-type doping of bilayered BiIrO3.
      Meanwhile, a spin-down polarized valley polarization of 79.5 meV can be induced
      in bilayered SrRuO3. The different thicknesses calculated demonstrate that the
      valley in the SrRuO3/BiIrO3 model is limited to the bilayered structure. The
      tunable valley and spin polarizations in SrRuO3/BiIrO3 superlattices would enrich
      the diversity and boost the development of high-performance spintronic and
      valleytronic devices.

PMID- 30229760
TI  - Disorder in the hydrogen-atoms uninvolved in hydrogen bonds in a metal-organic
      framework.
AB  - Organic and hybrid materials are emerging classes of materials with interesting
      properties inclusive of ferroelectric and magnetic ordering. They also offer the
      possibility of proton disorder that is of fundamental importance and useful for
      applications. In materials that exhibit proton disorder, such disordered-protons
      usually participate in the hydrogen bonds. Unlike the cations that host the
      disordered-sites, it is discovered in metal guanidinium formates
      (C(NH2)3M2+(HCOO)3) that the proton disorder is in the anionic framework. This
      study based on single-crystal neutron diffraction uncovers the presence of
      disorder in the formato-hydrogens of metal guanidinium formates regardless of
      their symmetry. The target materials exhibit various types of potential energy
      surfaces. Here the proton disorder for the first time is identified in the
      hydrogen atoms that neither participate in the hydrogen bonds nor in
      physisorption. A future challenge is to understand the influence of this
      phenomenon on the physicochemical properties of various classes of materials.

PMID- 30229761
TI  - Stable structures and superconductivity of an At-H system at high pressure.
AB  - The phase diagram, electronic properties and superconductivity of an At-H system
      at high pressure are investigated through first principles calculation
      considering the effect of spin-orbit coupling (SOC). The Cmcm-AtH2, Pnma-AtH2,
      P6/mmm-AtH4, and Cmmm-AtH4 phases are uncovered above 50 GPa. Metallization is
      realized at 50 GPa for AtH2 and 60 GPa for AtH4, with Tc values of approximately
      5-10 K and 30-50 K, respectively. In P6/mmm-AtH4, phonon softening induced by
      Fermi surface nesting occurs as the pressure increases, which is closely related
      to the structural phase transition of P6/mmm -> Cmmm and plays a crucial role in
      the superconductivity of the P6/mmm phase. In addition, the spin-orbit coupling
      effect considerably influences the energy of ground states, pressure points of
      phase transitions, electronic structures, and even the electron-phonon coupling
      of the At-H system. Such an influence may also occur in other heavy atomic
      hydrides.

PMID- 30229762
TI  - A skeletal double gyroid formed by single coaxial bundles of catechol based
      bolapolyphiles.
AB  - A bolapolyphile, derived from a linear p-terphenyl core with glycerol groups at
      each end and two octadecyl chains fixed to the same side of the pi-conjugated
      rod, is synthesized and is found to form a new type of self-assembled cubic LC
      phase with the Ia3[combining macron]d lattice. Each unit cell involves 16 polar
      aggregates interconnected by 24 coaxial rod-bundles at the single-molecule
      length, forming two interwoven skeletal networks with three-way junctions, being
      separated by a continuum of the lateral alkyl chains located around the gyroid
      minimal surface.

PMID- 30229763
TI  - Photoprotection or photodamage: a direct observation of nonradiative dynamics
      from 2-ethylhexyl 4-dimethylaminobenzoate sunscreen agent.
AB  - Apart from being an analogue of the prototype for photoinduced intramolecular
      charge transfer (ICT), 2-ethylhexyl 4-dimethylaminobenzoate (EHDMABA) is also one
      of the earliest patented and most commonly used sunscreen components. There is,
      however, little documented information about the photophysics and factors
      affecting the photophysics of this molecule. Such information is of importance
      for both the understanding of the ICT reaction and assessing the underlying
      process of photoprotection, especially in view of the "sunscreen controversy"
      that has arisen from the contrasting in vivo vs. in vitro photobiological results
      on this and related UV filters. We report herein a femtosecond broadband time
      resolved fluorescence (fs-TRF), complemented by transient absorption (fs-TA) to
      allow a full probe of the excited state cascades for EHDMABA and two of its
      derivatives in solvents of varied properties. The results provide direct evidence
      for a nearly solvent independent inner sphere ICT reaction occurring on the sub
      picosecond time scale, and an ensuing solvent dictated deactivation of the ICT
      state. The ICT state in the aprotic solvent acetonitrile decayed solely through
      the intrinsic intersystem crossing (ISC) to produce a potentially harmful triplet
      excited state. In the protic solvent, the solvation and formation of ICT-induced
      solute-solvent hydrogen (H)-bonding opened the originally inaccessible internal
      conversion (IC) channel of the ICT state, leading to the rapid reformation of the
      ground state molecule with a unitary efficiency in the aqueous solution. This H
      bonding-mediated IC restrained or eliminated the intrinsic ISC, providing a
      mechanism at the molecular level for the benign dissipation of the electronic
      excitation. The precise rate of IC was observed to vary with the alkoxy
      substituent and its efficiency was affected by the H-bonding capacity of the
      solvent. The findings of this work demonstrate the pivotal role of the
      microenvironment and the direct participation of solvent molecules through H
      bonding in drastically altering the nonradiative dynamics and promoting or
      inhibiting photostability and photoprotection. This may assist in developing next
      generation UV filters and help in improving formulation design for the optimal
      efficacy of sunscreen products. The pronounced H-bonding-induced fluorescence
      quenching and variation in the fluorescence wavelength imply that these molecules
      may also serve as a sensitive fluorescence probe for the H-bonding properties of
      the microenvironment.

PMID- 30229764
TI  - Polarization propagator theory and the entanglement between MO excitations.
AB  - Entanglement is at the core of quantum physics and so, one may conjecture that it
      should have some influence on atomic and molecular response properties. The usual
      way of treating entanglement is by applying information theory via the von Newman
      entropy. Given that the principal propagator is the operator that contains the
      physical information that arises due to the transmission of the effects of two
      external perturbations through the electronic framework of a quantum system, it
      should have in it the information necessary to quantify the likely entanglement
      among molecular orbital excitations. In this article we first propose a proper
      density matrix and from it, the way to quantify entangled excitations by using
      information theory. The NMR J-couplings are among the best candidates to learn
      about the potentialities of this formalism. We applied this new tool to analyze
      the famous Karplus rule and found a relationship between the dihedral angular
      dependence and the entanglement. We also found that the entangled excitations are
      related to electron correlation. The new formalism can be applied to all other
      response properties.

PMID- 30229765
TI  - Multi-scale theoretical approach to X-ray absorption spectra in disordered
      systems: an application to the study of Zn(ii) in water.
AB  - We develop a multi-scale theoretical approach aimed at calculating from first
      principles X-ray absorption spectra of liquid solutions and disordered systems.
      We test the method by considering the paradigmatic case of Zn(ii) in water which,
      besides being relevant in itself, is also of interest for biology. With the help
      of classical molecular dynamics simulations we start by producing bunches of
      configurations differing for the Zn(ii)-water coordination mode. Different
      coordination modes are obtained by making use of the so-called dummy atoms
      method. From the collected molecular dynamics trajectories, snapshots of a more
      manageable subsystem encompassing the metal site and two solvation layers are cut
      out. Density functional theory is used to optimize and relax these reduced system
      configurations employing a uniform dielectric to mimic the surrounding bulk
      liquid water. On the resulting structures, fully quantum mechanical X-ray
      absorption spectra calculations are performed by including core-hole effects and
      core-level shifts. The proposed approach does not rely on any guessing or fitting
      of the force field or of the atomic positions of the system. The comparison of
      the theoretically computed spectrum with the experimental Zn K-edge XANES data
      unambiguously demonstrates that among the different a priori possible geometries,
      Zn(ii) in water lives in an octahedral coordination mode.

PMID- 30229766
TI  - Rhodium(iii)-catalyzed C-H activation at the C4-position of indole: switchable
      hydroarylation and oxidative Heck-type reactions of maleimides.
AB  - A Rh(iii)-catalyzed C-H activation of indole at the C4-position leading to novel
      and switchable functionalization has been reported by employing a weakly co
      ordinating COCF3 group as a directing group. An additive plays an important role
      in switching the selectivity between 1,4-addition products and Heck-type
      products. An acid additive led to the formation of 1,4-addition products whereas
      a base additive promotes the formation of Heck-type products. Deuteration studies
      and control experiments were helpful to propose the mechanism.

PMID- 30229767
TI  - PVDF-MWNT interactions control process induced beta-lamellar morphology and
      orientation in the nanocomposites.
AB  - The effect of methylene blue (MB) modified multiwall carbon nanotubes (MWNTs) on
      the nucleation and morphology of polyvinylidene fluoride (PVDF) in comparison
      with the effect of MWNTs was systematically assessed by DSC, 13C NMR, FT-IR, TEM,
      WAXS and SAXS analysis. TEM analysis of ultra-microtomed samples revealed that MB
      modification enhanced the dispersibility of MWNTs in PVDF. Further, the
      nanocomposites were subjected to mechanical rolling and the synergistic effect of
      processing and fillers on the PVDF morphology (before and after rolling) at
      different length scales was studied. Both FT-IR and WAXS analyses suggested that
      mechanical rolling transforms alpha-PVDF to beta-PVDF (ca. 88%). TEM and two
      dimensional WAXS analyses revealed that the MWNTs and beta-crystallites are
      oriented preferentially along the rolling direction and the degree of orientation
      is not influenced by the fillers suggesting that crystallite orientation is fully
      controlled by mechanical rolling. On the other hand, beta-lamellae showed
      perpendicular orientation with respect to the rolling direction. Unlike beta
      crystallites, the beta-lamellar morphology and orientation are highly governed by
      the fillers as evident from SAXS analysis. Using MWNTs and the MWNT-MB pi
      complex, we demonstrate that the beta-lamellar morphology and degree of
      orientation are controlled by the extent of interaction of fillers with PVDF.
      Interestingly, both beta-lamellar morphology and degree of orientation correlate
      well with the mechanical properties of the rolled PVDF. More specifically, the
      dynamic storage modulus of the samples in the rolling direction increases with
      increasing beta-lamellar morphology and degree of orientation. The present work
      demonstrates that the polymer-filler interaction plays a crucial role in
      regulating the processed polymer morphology and can be tuned by appropriately
      modifying the surface of fillers through either covalent or non-covalent
      interactions.

PMID- 30229770
TI  - Facile synthesis of a metal-organic framework nanocarrier for NIR imaging-guided
      photothermal therapy.
AB  - The NIR dye cyanine (Cy) is one of the most significant phototherapy agents
      (PTAs) due to its strong NIR absorbance, high thermal conversion capacity and
      good safety. However, its clinic application is seriously limited owing to its
      inherent properties as an organic dye, including low solubility, poor
      selectivity, and fast clearance. Thus, herein, we embed Cy into the zeolitic
      imidazolate framework-8 (Cy@ZIF-8) for antitumor photothermal therapy (PTT). The
      obtained Cy@ZIF-8 NPs not only have good water solubility and excellent
      photostability, but also exhibit strong NIR absorbance and great photothermal
      conversion efficiency. Especially, the Cy@ZIF-8 NPs efficaciously inhibit tumor
      growth and possess outstanding NIR imaging capacity both in vitro and in vivo.
      This work demonstrates the theranostic value of Cy@ZIF-8 NPs for imaging-guided
      PTT therapy, and also encourages the further study of other PTAs@ZIF-8 composites
      for better anticancer PTT.

PMID- 30229769
TI  - Tuning the photoreactivity of Z-hexatriene photoswitches by substituents - a non
      adiabatic molecular dynamics study.
AB  - To understand how substituents can be used to increase the quantum yield of
      photochemical electrocyclic ring-closing of the Z-hexa-1,3,5-triene (HT)
      photoswitch forming cyclohexadiene (CHD), we investigate the S1 photo dynamics of
      HT and its derivatives 2,5-dimethyl-HT (DMHT), 2-isopropyl-5-methyl-HT (2,5
      IMHT), 1-isopropyl-4-methyl-HT (1,4-IMHT), and 2,5-diisopropyl-HT (DIHT) using
      time-dependent density functional theory surface hopping dynamics. We report
      detailed photoproduct distributions, formation mechanisms, branching ratios, and
      wavelength-dependent product quantum yields. Most products have been confirmed
      experimentally and include all-trans HT derivatives, cyclopropanes, cyclobutenes,
      cyclopentene, cyclohexadienes, and bicyclic compounds. Regarding CHD formation,
      we find that for the 2,5-substituted derivatives DMHT, 2,5-IMHT, and DIHT, the
      branching ratios increase with increasing size of the substituents. In contrast
      the branching ratios of the E/Z-isomerization decrease with increasing size of
      the substituents. Due to steric interactions, increasing the size of the
      substituents increases the amount of gZg rotamers in the ground state, which are
      prone to CHD formation and have lower E/Z-isomerization probability. Furthermore,
      we find [1,4], [1,5], and [1,6]-sigmatropic hydrogen shift reactions occurring at
      large percentages (5% to 15%); for sterical reasons these reactions stem from tZg
      conformers. DIHT shows the lowest percentage of side product formation among the
      2,5-substituted molecules and highest CHD branching ratio; its CHD quantum yield
      can be increased up to more than 64%, by excitation of DIHT on the red tail of
      its absorption spectrum, whereas the Z/E-isomerization is reduced below 5% and
      side reactions practically vanish. This makes DIHT the best candidate for
      applications in molecular switches.

PMID- 30229768
TI  - Unimicellar hyperstars as multi-antigen cancer nanovaccines displaying clustered
      epitopes of immunostimulating peptides.
AB  - Unimicellar hyperstar macromolecular chimeras displaying multiple melanoma
      peptide antigens were prepared primarily via a combination of click chemistry and
      esterification reactions starting from a biodegradable hyperbranched polymer
      template. Solubilization of the hyperstars in aqueous solution afforded a multi
      antigen unimicellar cancer nanovaccine of about 20 nm. The nanovaccine showed
      good biocompatibility and uptake by dendritic cells in vitro. An in vivo
      evaluation of the nanovaccine therapeutic efficacy against melanoma in mice
      implanted with B16OVA tumors revealed significantly greater T-cell recruitment
      and improved survival rates for mice treated with nanovaccine and adjuvant
      compared to non-treated mice.

PMID- 30229771
TI  - Low-intensity focused ultrasound (LIFU)-activated nanodroplets as a theranostic
      agent for noninvasive cancer molecular imaging and drug delivery.
AB  - Theranostics is a new trend in the tumor research field, which involves the
      integration of diagnostic and therapeutic functions using imageable nanoparticles
      coupled with therapeutic drugs. Imaging-guided targeted delivery of therapeutics
      and diagnostics using nanocarriers hold great promise to minimize the side
      effects of conventional chemotherapy. Ultrasound microbubbles have been employed
      as theranostic agents over the last decade, which provide both real-time dynamic
      imaging for diagnosis and precise control for targeted tumor therapy. However,
      the intrinsic defects of microbubbles such as poor tissue penetration, short
      circulation time and instability hinder microbubble-based theranostic
      applications. In recent years, liquid-to-gas transitional perfluorocarbon
      nanoparticles have been developed as promising diagnostic and therapeutic
      nanoagents to solve the abovementioned problems. In this study, phase-changeable,
      folate-targeted perfluoropentane nanodroplets loaded with 10-hydroxycamptothecin
      (HCPT) and superparamagnetic Fe3O4 (denoted as FA-HCPT-Fe3O4-PFP NDs) are
      prepared and investigated for multimodal tumor imaging and targeted therapy.
      After intravenous administration into nude mice bearing SKOV3 ovarian cancer, FA
      HCPT-Fe3O4-PFP NDs exhibit the ability to enhance MR and PA imaging. Furthermore,
      after the phase transition activated by low-intensity focused ultrasound (LIFU)
      sonication, FA-HCPT-Fe3O4-PFP NDs remarkably enhance US imaging at the tumor
      location. Meanwhile, the HCPT released from FA-HCPT-Fe3O4-PFP NDs during the
      liquid-to-gas transition provides a therapeutic effect on tumor cells with
      relatively low side effects to normal tissue. Therefore, the combination of LIFU
      and FA-HCPT-Fe3O4-PFPNDs presents an ideal modality for tumor-targeted
      theranostics.

PMID- 30229772
TI  - Large amplitude motions within molecules trapped in solid parahydrogen.
AB  - Molecules of the beta-diketone and beta-dialdehyde families were trapped in solid
      parahydrogen (pH2) to investigate the vibrational behavior of systems containing
      an intramolecular hydrogen bond (IHB). In the simplest beta-diketone,
      acetylacetone (AcAc), H transfer related to the IHB is coupled with methyl
      torsions. In pH2, the study of nuclear spin conversion (NSC) in methyl groups
      allows the characterisation of the influence of these large amplitude motions on
      the vibrational modes. The deuteration of the OH group involved in the IHB has
      important consequences on the vibrational spectrum of the molecule and evidence
      of NSC in methyl groups is difficult to obtain. In the chlorine derivative (3
      chloroacetylacetone), the H-transfer is no longer coupled with methyl torsion,
      and NSC has undetectable effects on the IR spectrum. A search of H tunnelling
      splitting in the IR spectra of beta-dialdehydes trapped in pH2 was performed. A
      few modes of 2-chloromalonaldehyde appear as doublets and were assigned to
      tunnelling levels. The spectroscopic results related to large amplitude motions
      are detailed and discussed, highlighting puzzling effects.

PMID- 30229773
TI  - Stereochemistry-dependent hydrogen bonds stabilise stacked conformations in jet
      cooled cyclic dipeptides: (LD) vs. (LL) cyclo tyrosine-tyrosine.
AB  - Tyrosine-containing cyclic dipeptides based on a diketopiperazine (DKP) ring are
      studied under jet-cooled conditions using resonance-enhanced multi-photon
      ionisation (REMPI), conformer-selective IR-UV double resonance vibrational
      spectroscopy and quantum chemical calculations. The conformational landscape of
      the dipeptide containing natural L tyrosine (Tyr), namely c-LTyr-LTyr strongly
      differs from that of its diastereomer c-LTyr-DTyr. A similar family of conformers
      exists in both systems, with one aromatic ring folded on the dipeptide DKP ring
      and the other one extended. Weak NHpi and CHpi interactions are observed, which
      are slightly different in c-LTyr-LTyr and c-LTyr-DTyr. These structures are
      identical to those of LL and LD cyclo diphenylalanine, which only differ from c
      Tyr-Tyr by the absence of hydroxyl on the benzene rings. While this is the only
      conformation observed for c-LTyr-DTyr, c-LTyr-LTyr exhibits an additional form
      stabilised by the interaction of the two hydroxyls, in which the two aromatic
      rings are in a stacked geometry. Stereochemical effects are still visible in the
      radical cation, for which one structure is observed for c-LTyr-DTyr, while the
      spectrum of the c-LTyr-LTyr radical cation is explained in terms of two co
      existing structures.

PMID- 30229774
TI  - IR820 covalently linked with self-assembled polypeptide for photothermal therapy
      applications in cancer.
AB  - Owing to the unique advantages of high specificity and minimal invasiveness,
      photothermal therapy (PTT) has been evidenced with great potential in cancer
      treatment. However, most photothermal agents present a shortage of photobleaching
      and nonspecific biodistribution in clinical application. In this study, we
      conjugated a new Indocyanine Green Dye (IR820) with self-assembled polypeptide
      (ELP) via chemical bonding in an aqueous environment. This preparation method
      could effectively avoid damaging the polypeptide. ELP-IR820 was fabricated as
      nanoconjugates with diameters of approximately 50 nm. The use of ELP-IR820
      notably enhanced photothermal-mediated cytotoxicity on CT-26 cancer cells. We
      demonstrate that the ELP-IR820 nanoparticles significantly improved drug
      accumulation in the tumor and photothermal effect in vivo compared to the free
      dye and monomer ELP-IR820. ELP-IR820 nanoparticle also exhibited outstanding
      ability to cause prominent tumor tissue growth inhibition via the photothermal
      effect. No noticeable toxicity was detected for all treatment groups. These
      investigations broaden the application of NIR dyes as a multimodal photothermal
      therapy platform.

PMID- 30229775
TI  - Decellularized orthopaedic tissue-engineered grafts: biomaterial scaffolds
      synthesised by therapeutic cells.
AB  - In orthopaedic surgery, the reconstruction of musculoskeletal defects is a
      constant challenge. Biomaterials in tissue engineering are utilized as scaffolds
      which serve as templates for cell proliferation and secretion as well as guides
      for new tissue formation. The extracellular matrix (ECM) is a desirable
      biological scaffold due to its complex composition and three-dimensional
      ultrastructure, which drive the homeostasis and regeneration of tissues.
      Successfully used in a variety of regenerative medicine applications, ECM
      scaffolds can be achieved by decellularization of engineered tissue. In addition
      to using decellularized grafts directly as scaffolds, decellularized grafts can
      also be coated on or incorporated into synthetic biomaterials to substantially
      enhance their biological performance regarding integration into the surrounding
      tissue and bioactivity for neo-tissue generation. However, at present, the most
      widely adopted decellularized scaffolds are decellularized native scaffolds,
      which have the limitations of inherent heterogeneity, fixed shapes and
      insufficient sources. Decellularized tissue-engineered scaffolds are promising to
      avoid these restrictions and are receiving attention in the regenerative medicine
      field. This review describes the rationale of using decellularized tissue
      engineered grafts for different regenerative purposes and details their
      application in the repair of orthopaedic defects.

PMID- 30229776
TI  - Recent advances in the synthesis of cyclopropanes.
AB  - Cyclopropanes, one of the most important strained rings, have gained much
      attention for more than a century because of their interesting and unique
      reactivity. They not only exist in many natural products, but have also been
      widely used in the fields of organic synthesis, medicinal chemistry and materials
      science as versatile building blocks. Based on the sustainable development in
      this area, this review mainly focuses on the recent advances in the synthesis of
      cyclopropanes classified by the type of catalytic system, including regio-,
      diastereo-, and enantio-selective reactions.

PMID- 30229779
TI  - Redox modulation of polydopamine surface chemistry: a facile strategy to enhance
      the intrinsic fluorescence of polydopamine nanoparticles for sensitive and
      selective detection of Fe3.
AB  - In recent years, polydopamine (PDA) nanoparticles have attracted considerable
      attention in different research fields because of their many fascinating
      physicochemical properties. However, as an analogue of naturally occurring
      melanin, PDA nanoparticles (PDANPs) typically exhibit weak fluorescence
      properties. Herein, we report a facile one-pot method for synthesizing bright
      blue luminescent PDANPs through the redox modulation of PDA surface chemistry.
      The composition and morphology of the resultant NPs were systematically
      characterized by transmission electron microscopy and several spectroscopy
      methods, which verified the successful fabrication of PDANPs. More importantly,
      comparative chemical analysis of dopamine polymerization revealed the significant
      impacts of synthesis conditions and PDA surface chemistry on the luminescence
      properties of PDANPs. Remarkably, in addition to their excellent water
      solubility, salt-tolerance and high photostability under extreme pH conditions,
      the as-prepared PDANPs possess the highest quantum yield (5.1%) among all the
      reported intrinsic fluorescent PDANPs. Moreover, based on the coordination
      interaction between phenolic hydroxyl groups of PDANPs and ferric ions (Fe3+),
      the synthesized PDANPs were successfully utilized as a turn-off sensing platform
      for sensitive and selective detection of Fe3+ without using any additional
      targeting molecules. Upon increasing the Fe3+ concentration in the range from 0.5
      to 20 MUM, the fluorescence intensity of PDANPs decreased linearly. The detection
      limit of Fe3+ was 0.15 MUM. Finally, this fluorescent sensor was successfully
      used to determine Fe3+ in natural water samples, showing good prospects for
      practical applications and may pave the way for the development of new rational
      methodologies for further enhancing the intrinsic fluorescence of PDA and
      fabricating other novel fluorescent organic nanoparticles.

PMID- 30229780
TI  - Chromium sulfide halide monolayers: intrinsic ferromagnetic semiconductors with
      large spin polarization and high carrier mobility.
AB  - Two-dimensional (2D) ferromagnetic semiconductors (FMSs) are desirable for their
      potential to enhance the functionality of semiconductor devices via the
      utilization of spin degrees of freedom. Herein, we predict a series of intrinsic
      FMS monolayers in the chromium sulfide halide CrSX (X = Cl, Br, I) family with
      large spin polarization, large magnetic moments and high Curie temperatures. Such
      CrSCl and CrSBr monolayers also have high hole mobilities up to 6.6 * 103 and 5.3
      * 103 cm2 V-1 s-1, respectively. Furthermore, these 2D monolayers exhibit
      excellent dynamic and thermal stabilities and a small exfoliation energy from the
      bulk. These intrinsic FMSs with their high mobilities may provide competitive
      candidates for next-generation spintronics and electronics.

PMID- 30229781
TI  - Regioselective N-1 and C-2 diacylation of 3-substituted indoles with arylglyoxal
      hydrates for the synthesis of indolyl diketones.
AB  - A highly regioselective N-1 and C-2 diacylation of 3-substituted indoles with
      arylglyoxal hydrates to afford N-1 and C-2 indolyl diketones in moderate to good
      yields is described. Notably, the control of regioselectivity is achieved by
      small changes in the Cu catalyst, additive and solvent. Importantly, the
      intermediates for N-1 and C-2 diacylation were detected and two plausible
      pathways were also proposed.

PMID- 30229782
TI  - Nanoscale coherent interface strengthening of Mg alloys.
AB  - Structural materials with higher strength and ductility could reduce weight and
      improve energy efficiency from the ecological and economical viewpoints. However,
      most classical strengthening strategies, such as refining grain size and forming
      secondary particles, can effectively hinder dislocation motion but remarkably
      decrease ductility. In this research, a nanoscale contraction twins-stacking
      faults (CTWSFs) hierarchical structure was achieved in a model sample of
      magnesium-lithium (Mg-Li) alloy using an industrial ultrahigh pressure technique.
      The specific yield strength and elongation of the treated Mg-Li alloy were ~179
      kN m kg-1 and ~25% at room temperature, respectively. Both of these are the
      highest values reported so far, even compared to commercial aluminum alloys and
      steel. Depending on molecular dynamics simulations, it was demonstrated that the
      basal-plane stacking faults (SFs) attribute to the nucleation of contraction
      twins (CTWs), but prevented the broadening of the CTWs. The results were
      confirmed using ex situ transmission electron microscopy. The models also
      verified that the unique structure of nanoscale coherent boundaries-basal-plane
      SFs were effective in preventing dislocation motion in a single Mg crystal, which
      was analogous to twin boundaries. Finding this new CTWSFs structure might provide
      an alternative perspective for designing more innovative hexagonal close packed
      (hcp)-type structural materials with superior mechanical properties.

PMID- 30229783
TI  - Broadband 1T-titanium selenide-based saturable absorbers for solid-state bulk
      lasers.
AB  - 1T-titanium selenide (1T-TiSe2), a representative of 1T phase transition metal
      dichalcogenides (TMDs), exhibits semimetallic behaviour with a nearly zero
      bandgap structure, which makes it a promising photoelectric material. A high
      quality multilayer 1T-TiSe2 saturable absorber (SA) is successfully fabricated by
      a combination of liquid phase exfoliation and the spin coating method. The
      broadband nonlinear saturable absorption properties of the prepared 1T-TiSe2 SA
      are investigated by using the open aperture (OA) Z-scan method. Passively Q
      switched (PQS) all-solid-state lasers with different bulk crystals at the
      wavelengths of 1.0, 1.3, 2.0 and 2.8 MUm are realised based on the 1T-TiSe2 SA.
      To the best of our knowledge, this is the first presentation of the application
      of a 1T-TiSe2 material to all-solid-state bulk lasers. The results indicate that
      1T-TiSe2 could be an alternative broadband SA for solid-state pulsed lasers and
      exhibits promising potential applications in mode-locked ultrafast lasers.

PMID- 30229784
TI  - Enantioselective synthesis of alpha-perfluoroalkylated prolines, their 6,7
      membered homologues and derivatives.
AB  - Enantioselective synthesis of alpha-perfluoroalkylated cyclic amino acids and
      their derivatives was elaborated using the organocatalytic Strecker reaction with
      5-7 membered cyclic ketimines. The prepared amino nitriles could be transformed
      into chiral Rf-prolines and their 6,7-membered homologues as well as their
      corresponding amides and diamines (yields up to 99%, up to >99% ee).

PMID- 30229787
TI  - Synthesis and properties of dithienylethene-functionalized switchable
      antibacterial agents.
AB  - Photopharmacology involving azobenzene has offered a viable alternative for
      combating bacterial resistance. However, the degradation and potential toxicity
      of azobenzene limit its further study in vivo. Therefore, searching for an
      appropriate photoswitch for further clinical application is highly desirable.
      Herein a series of dithienylethene-functionalized switchable antibacterial agents
      have been designed and prepared by the introduction of the dithienylethene
      scaffold into fluoroquinolones. And it was found that these switchable
      antibacterial agents displayed good photochromism and fluorescence switching
      behaviors upon irradiation with UV/Vis light in DMSO. Surprisingly, methoxy
      substituted dithienylethenes 3a and 3b exhibited fluorescence turn-on behavior.
      Furthermore, it was found that all of the open-isomers showed partial
      antibacterial activity on E. coli and S. aureus compared with the native drugs.
      Apart from 2a and 2b, the other switchable antibacterial agents showed a large
      difference in antibacterial activity on Gram-negative E. coli between the open
      and closed forms, in which the antimicrobial activity of the ring-closed isomers
      for 1b and 3b was 16 times that of the corresponding ring-open isomers. DFT
      calculations showed that the ring-closed isomers of 1b and 3b presented a rigid
      "S-type" conformation, which may be conducive to forming more stable complexes
      with the DNA gyrase of E. coli.

PMID- 30229788
TI  - Serum protein corona-responsive autophagy tuning in cells.
AB  - Autophagy represents an important cellular response to nanoparticles (NPs), whose
      modulation holds great promise for developing nanomedicine. Here, we
      systematically studied cell autophagy responses elicited by the NP-protein corona
      with diverse protein corona types surrounding NPs with different sizes, shapes,
      and compositions. We demonstrated that these physicochemical properties of NP
      protein coronas exerted a remarkable influence on cell autophagy responses.
      Particularly, for surface protein type-associated modulation of cell autophagy,
      we correlated the autophagy level to adsorbed protein type on Fe3O4 NPs.
      Accordingly, we could modulate cell autophagy in response to various levels of
      protein adsorption. Our work provides new clues to modulate cell autophagy by
      rational designing NP-protein complexes, which could aid in further biological
      and therapeutic applications.

PMID- 30229789
TI  - Dirhodium(ii)-catalyzed ortho C-H amination of sterically congested N,N
      dialkylanilines.
AB  - Dirhodium(ii)-catalyzed ortho C-H amination of N,N-dialkylanilines has been
      developed. Sterically congested 1,2-diaminobenzenes were obtained in high yields
      with excellent chemo- and regioselectivities from para-substituted anilines and
      even from para-unsubstituted anilines. The ortho selectivity observed was
      rationalized in terms of the interaction between the dialkylamino group and a
      Rh(ii)-nitrene intermediate.

PMID- 30229791
TI  - Biomimetic synthesis of the bisindole framework present in sciodole, an alkaloid
      from Tricholoma sciodes.
AB  - A synthesis of the unique bisindole framework present in the mushroom-derived
      alkaloid sciodole has been achieved, validating a biosynthesis proposal that the
      C-N bisindole bond present in the natural product is forged by amination of an
      azafulvenium.

PMID- 30229790
TI  - Heavy doping of ceria by wet impregnation: a viable alternative to bulk doping
      approaches.
AB  - To avoid the deleterious effects of dopant segregation, synthesis methods that
      facilitate a homogenous dopant distribution in the ceria lattice were employed.
      Though doping ceria by wet impregnation was also credited to induce a homogeneous
      solid solution even in the heavy regime (concentration >=20%, A. Corma, P.
      Atienzar, H. Garcia and J. Chane-Ching, Nat. Mater., 2004, 3, 394-397), no follow
      up investigation has been reported. Herein, we investigated ceria nanoparticles
      (1%Tm-CeO2 and 1%Eu-CeO2) wet-impregnated with trivalent rare-earth (Yb, 20%),
      bivalent (Ca, 20%) and isovalent (Zr, 30%) metals, followed by annealing in air.
      Homogeneity of the solid solutions of Yb-impregnated ceria was confirmed by a two
      feature characterization toolbox that included X-ray diffraction, Raman
      spectroscopy, transmission electron microscopy, as well as up-conversion emission
      as a probe tool. Since the up-conversion emission of Tm was not detectable in the
      absence of Yb while its efficiency depends on the average distance between Yb and
      Tm ions, the Yb incorporation and its migration from the surface to the lattice
      bulk sites in wet-impregnated ceria can be "visualized" and compared with that of
      the Yb bulk-doped counterpart. The use of Eu luminescence as a local probe
      confirmed the homogeneity of solid solutions of Ca and Zr-impregnated ceria and
      also sustained the opposite roles of Ca and Zr as the repeller and the scavenger
      of oxygen vacancies, respectively. All these results suggested that heavy doping
      of ceria by wet impregnation with metals with +2, +3 and +4 valencies represent a
      facile alternative to conventional doping approaches. Therefore, the effects of
      the amount and the type of metal dopant on the structural properties of CeO2
      could be investigated in a more systematic and probably a more reproducible
      manner, which would significantly increase the potential of ceria in catalysis
      and other applications.

PMID- 30229793
TI  - Sialylated variants of lacto-N-tetraose exhibit antimicrobial activity against
      Group B Streptococcus.
AB  - Human milk oligosaccharides (HMOs) possess antimicrobial activity against a
      number of bacterial pathogens. HMOs prevent infection by serving as decoy
      receptors that competitively bind pathogens thus preventing pathogen attachment
      to host epithelial cell receptors. In a second mechanistic pathway, we recently
      demonstrated that heterogenous HMO extracts exert antimicrobial action against
      Group B Streptococcus by increasing cellular permeability. As human milk contains
      ca. 200 unique glycans however, our understanding of which pharmacophores are
      most important to HMO antimicrobial activity remains immature. In the present
      study, we describe the first evaluation of the antimicrobial and antibiofilm
      activities of five structurally defined, ubiquitous sialylated HMOs against Group
      B Streptococcus.

PMID- 30229794
TI  - Cyclic imines - preparation and application in synthesis.
AB  - The chemistry of cyclic imines has been gaining importance in the last decade
      because of their broad spectrum of applications and biological importance. This
      review focuses on the synthesis and utilization of these compounds with an
      emphasis on strategic transformations in organic chemistry. Electron-deficient
      sulfamate-derived and N-sulfonyl cyclic imines are also discussed as examples of
      versatile synthons in organic synthesis.

PMID- 30229795
TI  - Morphology modulation in evaporative drying mediated crystallization of sodium
      chloride solution droplet with surfactant.
AB  - We report the evaporative drying of an aqueous droplet containing a dilute
      solution of sodium chloride (NaCl) on a hydrophobic substrate made of cross
      linked poly-dimethyl siloxane (PDMS). The salt concentration Cn was varied
      between 0.08 molar (M) and 2.0 M. The contact line of the evaporating droplets
      shows significant initial retraction for all Cn, before they get pinned. While
      the final morphology comprises a few small NaCl crystals deposited around the
      pinned contact line, in droplets with a low Cn (<0.5 M), it transforms to a
      single large salt crystal when Cn > 0.7 M with no peripheral deposition. We
      further show that the deposition morphology drastically changes when an anionic
      surfactant, sodium dodecyl sulfate (SDS), is added into the salt-solutions. Even
      in the surfactant-laden droplets, the final deposition morphology changes
      significantly as a function of Cn. It transforms from a thick SDS ring
      surrounding a fractal-like deposit of NaCl crystallites at lower Cn to a
      peripheral deposit of NaCl crystals at higher Cn due to competition between
      micelle formation and crystallization. However, the crystallographic orientation
      of the deposited NaCl crystals remains unaltered irrespective of the presence of
      surfactant.

PMID- 30229796
TI  - Stereoselective synthesis of 1,3-disubstituted dihydroisoquinolines vial
      phenylalanine-derived dihydroisoquinoline N-oxides.
AB  - The preparation of chiral pool-derived nitrone 3 and its use in the protecting
      group free, stereoselective synthesis of a range of 1,3-disubstituted
      tetrahydroisoquinolines is described. Grignard reagent additions to nitrone 3
      yielded trans-1,3-disubstituted N-hydroxytetrahydroisoquinolines 6 with good
      levels of selectivity, while 1,3-dipolar cycloadditions to this nitrone provided
      access to 3-(2-hydroxyalkyl)isoquinolines 12 as single diastereomers.

PMID- 30229797
TI  - A convenient synthetic route towards H-bisphosphinates.
AB  - A practical generalisable procedure to synthesize hydroxymethylene H
      bisphosphinates has been optimised. Unlike previous reports, numerous alkyl
      (including an alendronate bisphosphinate analogue) or (hetero)aryl compounds were
      rapidly obtained in satisfactory to excellent yields. A side product could have
      been identified as a phosphino-phosphonate isomer and plausible mechanistic
      pathways are proposed here. Moreover to check the literature data, a pKa value
      study was also performed.

PMID- 30229798
TI  - Stereo- and regioselective photocycloaddition of extended alkenes using gamma
      cyclodextrin.
AB  - Photoexcitation of dibenzalacetones (1a-d) in homogeneous media and solid state
      yields a mixture of products with poor conversions. Irradiation of the reactants
      complexed to gamma-cyclodextrin predominantly affords a single dimer (syn adduct
      6) despite the possibility for several monomeric and dimeric products. High
      selectivity in the cavitand-mediated reaction along with the structural
      characterization of the inclusion complex provides insight into the
      supramolecular interactions that drive the self-assembly of the host-guest
      system.

PMID- 30229799
TI  - Self-assembly of a redox-active bolaamphiphile into supramolecular vesicles.
AB  - The synthesis and self-assembly of a water-soluble bolaamphiphilic
      cyclopenta[hi]aceanthrylene derivative is described. Self-assembly in aqueous
      medium leads to the formation of supramolecular vesicles with intense absorption
      bands over an extended range of the UV/vis spectral region and a narrow HOMO-LUMO
      bandgap of 1.65 eV.

PMID- 30229800
TI  - Light-driven exchange between extended and contracted lasso-like isomers of a
      bistable [1]rotaxane.
AB  - The synthesis of a set of benzylic amide [1]rotaxanes via a self-templating
      clipping approach is described. This methodology supposes the 1 + 1 coupling of
      isophthaloyl dichloride with an acyclic diamine precursor incorporating a
      templating arm. The structure of the threaded compounds was determined both in
      solution and in the solid state. The conversion into the corresponding unthreaded
      isomers, also obtained by deslipping of [2]rotaxane models, was evaluated in
      competitive and non-competitive hydrogen-bonding solvents. The switch of the
      extended and contracted lasso-like isomers of a bistable [1]rotaxane by an olefin
      isomerization promoted by UV light irradiation was also accomplished and their
      ring positional integrity was examined.

PMID- 30229801
TI  - Rhodium(iii)-catalyzed three-component cascade synthesis of 6H-benzo[c]chromenes
      through C-H activation.
AB  - A three-component cascade reaction is described that provides concise access to
      6H-benzo[c]chromenes via Rh(iii)-catalyzed annulation of aryl ketone O
      acyloximes, quinones and acetone. Acetone acts as a co-solvent and as a reactant.
      This reaction shows high efficiency, atom- and step-economy, good substrate
      scope, excellent functional group compatibility and gives the products in good
      yields.

PMID- 30229802
TI  - Meniscus instabilities in thin elastic layers.
AB  - We consider meniscus instabilities in thin elastic layers perfectly adhered to,
      and confined between, much stiffer bodies. When the free boundary associated with
      the meniscus of the elastic layer recedes into the layer, for example by pulling
      the stiffer bodies apart or injecting air between them, then the meniscus will
      eventually undergo a purely elastic instability in which fingers of air invade
      the layer. Here we show that the form of this instability is identical in a range
      of different loading conditions, provided only that the thickness of the
      meniscus, a, is small compared to the in-plane dimensions and to two emergent in
      plane length scales that arise if the substrate is soft or if the layer is
      compressible. In all such situations, we predict that the instability will occur
      when the meniscus has receded by approximately 1.27a, and that the instability
      will have wavelength lambda ~ 2.75a. We illustrate this by also calculating the
      threshold for fingering in a thin wedge of elastic material bonded to two rigid
      plates that are pried apart, and the threshold for fingering when a flexible
      plate is peeled from an elastic layer that glues the plate to a rigid substrate.

PMID- 30229808
TI  - LncRNA HOTTIP mediated DKK1 downregulation confers metastasis and invasion in
      colorectal cancer cells.
AB  - Recent studies highlight long non-coding RNAs (lncRNAs) as key regulators of
      cancer biology that contribute to carcinogenesis. The lncRNA HOXA transcript at
      the distal tip (HOTTIP) is involved in the development of several cancers.
      Previous studies demonstrated that HOTTIP could promote colorectal cancer (CRC)
      cell proliferation via silencing of p21 expression. However, the potential role
      of HOTTIP in CRC metastasis has not yet been discussed. Here, we found that
      HOTTIP level was significantly higher in CRC than in corresponding adjacent
      normal tissues, and patients with a larger tumor size, advanced pathological
      stage, or distant metastasis had higher HOTTIP expression. Moreover, silencing
      HOTTIP expression by siRNA or shRNA could inhibit CRC cell migration and invasion
      in vitro and in vivo, whereas HOTTIP overexpression promoted cell metastasis, as
      documented in the SW480 cell lines. Mechanistic analyses indicated that HOTTIP
      regulates CRC cell metastasis partly through the downregulation of tumor
      suppressor DKK1 expression. Collectively, our results suggest that tumor
      expression of lncRNA HOTTIP plays an important role in CRC metastasis. HOTTIP may
      serve as a candidate biomarker in this disease.

PMID- 30229809
TI  - Comment on: Correlation between HSD17B4 expression in rat liver cancer tissues
      and inflammation or proliferation.

PMID- 30229810
TI  - The Territorial Ethics Committee after approval of Italian Law No. 220/2017.

PMID- 30229811
TI  - Over-expressed miR-27a-3p inhibits inflammatory response to spinal cord injury by
      decreasing TLR4.
AB  - OBJECTIVE: We investigate whether microRNA-27a-3p (miR-27a-3p) can inhibit the
      inflammatory response of spinal cord injury by negatively regulating toll-like
      receptor 4 (TLR4). PATIENTS AND METHODS: The quantitative Real-time polymerase
      chain reaction (qRT-PCR) assay was used to detect the expression of miR-27a-3p
      and TLR4 in serum samples from patients with spinal cord injury and in hydrogen
      peroxide-treated C8-B4 and C8-D1A cells. Dual luciferase reporter assays were
      used to detect targeted binding of TLR4 to miR-27a-3p. The protein expression of
      miR-27a-3p and TLR4 and the two inflammatory factors, tumor necrosis factor alpha
      (TNF-alpha) and interleukin 6 (IL-6), were all detected by Western blot. RESULTS:
      TLR4 expression was elevated and miR-27a-3p was decreased in serum samples from
      patients with spinal cord injury and in hydrogen peroxide-treated C8-D1A and C8
      B4 cells. Dual luciferase reporter assays results demonstrated that miR-27a-3p
      can bind to TLR4. Up-regulation of miR-27a-3p can decrease the expression of TNF
      alpha and IL-6 and can also reduce TLR4 expression. After overexpression of TLR4,
      the expression of TNF-alpha and IL-6 were increased. CONCLUSIONS: miR-27a-3p can
      inhibit the inflammatory response of spinal cord injury by negatively regulating
      TLR4.

PMID- 30229812
TI  - Investigation for the role of CTX-III and microRNA-98 in diagnosis and treatment
      of osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis is a joint degeneration and proliferative inflammatory
      disease caused by obesity, joint deformities, trauma, and other factors. C
      terminal collagen (CTX) is associated with cartilage degradation, and healthy
      cartilage state is one of the factors that affect osteoarthritis. microRNA-98
      (miRNA-98) plays a role in inflammation. This study aims to investigate the
      levels of CTX-III and miRNA-98 in patients with osteoarthritis and their
      potential clinical usage. PATIENTS AND METHODS: Osteoarthritis was diagnosed
      according to the inclusion and exclusion criteria for osteoarthritis. Patients
      with osteoarthritis admitted to Jining No. 1 People's Hospital and healthy
      volunteers were included in this study. ELISA and Western blot analysis were used
      to detect levels of type III collagen CTX (CTX-III). Real time PCR was used to
      measure levels of miRNA-98 in the serum of both patients and healthy volunteers.
      RESULTS: Levels of CTX-III protein in osteoarthritis patients were significantly
      higher than that of healthy volunteers (p = 0.0013). Levels of miRNA-98 in the
      serum of osteoarthritis patients were significantly higher compared to that of
      healthy volunteers (p = 0.0065). After treatment, levels of CTX-III protein and
      serum miRNA-98 in patients with osteoarthritis were significantly decreased (p =
      0.014, p = 0.021). Levels of CTX-III protein and serum miRNA-98 in patients with
      osteoarthritis were significantly higher compared to that of healthy volunteers
      (p = 0.0013). CONCLUSIONS: Both of the CTX-III and microRNA-98 are potential
      diagnostic indicators for the osteoarthritis.

PMID- 30229813
TI  - Overexpression of miR-381-3p promotes the recovery of spinal cord injury.
AB  - OBJECTIVE: To study the effects of miR-381-3p on spinal cord injury and its
      underlying mechanism. MATERIALS AND METHODS: After the spinal cord injury rat
      model of was established, Sprague Dawley (SD) rats were randomly divided into the
      control group and the acute spinal cord injury (ASCI) group. Microglial BV2 cells
      were used as experimental cells, and the cells were divided into the control
      group and the lipopolysaccharide (LPS) group. The mRNA and protein expression
      level of miR-381-3p, IKKbeta, inflammatory factors, and p-p65 were detected by
      quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) and
      Western blot, respectively. Dual-luciferase reporter gene assay and Western blot
      were used to detect the regulatory effect of IKKbeta on miR-381-3p. Changes in
      grip ability and rotary performance of rats in the ASCI group were evaluated
      after miR-381-3p overexpression in vivo. RESULTS: The expression of miR-381-3p
      was downregulated in rats of the ASCI group, while the expression of IKKbeta and
      p-p65 were upregulated. In vitro experiments demonstrated that LPS could inhibit
      the expression of miR-381-3p and promote the upregulation of IKKbeta and p-p65.
      Overexpression of miR-381-3p could inhibit the mRNA and protein expression of
      IKKbeta. The upregulated expression of IKKbeta, p-p65, tumor necrosis factor
      alpha (TNF-alpha), and interleukins-1beta (IL-1beta) induced by LPS in BV2 cells
      were reversed by miR-381-3p mimic transfection. Besides, upregulated TNF-alpha
      and IL-1beta induced by miR-381-3p inhibitor in BV2 cells were reversed by
      IKKbeta inhibitor (BMS-345541). Results of animal experiments indicated that miR
      381-3p was overexpressed in rats of the ASCI group. The protein levels of IKKbeta
      and p-p65, and the mRNA expression levels of inflammatory cytokines TNF-alpha and
      IL-1beta were remarkably decreased in the ASCI group than those of the control
      group. The grip ability, coordination, and anti-fatigue performance of rats in
      the ASCI group recovered quicker than those of the control group. CONCLUSIONS:
      MiR-381-3p was downregulated in ASCI rats. The overexpression of miR-381-3p could
      recover the motor ability of rats in the ASCI group earlier and might inhibit
      injury aggravation by inhibiting inflammatory responses via the IKKbeta-NF-kappaB
      pathway.

PMID- 30229814
TI  - Osteoid osteoma treated with radiofrequency ablation in non-operating room
      anesthesia. A different way of approaching ablative therapy on osteoid osteoma.
AB  - OBJECTIVE: The purpose of this study is to verify the effectiveness and
      complications occurrence of radiofrequency ablation (RFA) in the treatment of
      osteoid osteoma (OO) in non-operating room anesthesia (N.O.R.A.). PATIENTS AND
      METHODS: From 2014 to 2017, 61 patients affected by OO (40 men and 21 women) with
      an age of 20.7 years on average (range, 4-51 years; 12 patients aged 20 years or
      younger) underwent computed tomography-guided percutaneous radiofrequency
      ablation (RFA) in N.O.R.A. (Non-Operating Room Anesthesia). Lesion sites treated
      were: femur (27), tibia (22), pelvis (2), talar bone (3), distal radius (1), and
      humerus (6). Mean follow-up time was 36 months. In each case, anesthesiologic
      support followed a new protocol (N.O.R.A. protocol), approved by our Institute.
      Primary success rate, complications, symptom-free intervals, and follow-up
      results were evaluated. RESULTS: Pain relief (evaluated with Visual Analogue
      Scale - VAS) was significant in 97% of patients; it disappeared within 24 hours
      of the procedure in 44 patients, within 3 days in 10 patients, and within 7 days
      in 7 patients. After 6 months of observation time, 60 of 61 patients were
      successfully treated and had no more complaints. In 2 patients, two major
      complications were found: infection of the site treated, healed with antibiotics,
      and a nerve lesion, healed with steroid therapy. No other complications were
      observed. CONCLUSIONS: RFA is a highly effective, efficient, minimally invasive
      and safe method for the treatment of OO following N.O.R.A. PROTOCOL: 

PMID- 30229815
TI  - Screening of parathyroid gland by high frequency ultrasound and the relationship
      between recurrent urinary calculi and primary hyperparathyroidism.
AB  - OBJECTIVE: To understand the value of high frequency ultrasound in the clinical
      screening of parathyroid gland, and to summarize the intrinsic relationship
      between primary hyperparathyroidism and recurrent urinary calculi. PATIENTS AND
      METHODS: 98 cases of urinary calculi were randomly selected, and the patients
      were admitted to our hospital from March 2014 to August 2017. A total of 100
      healthy subjects were selected as group B in the same period. High frequency
      color Doppler ultrasonography scan recorded the results. RESULTS: Among the
      subjects in group A, 67 (68.37%) showed parathyroid gland, 14 cases (14.29%) had
      tumor mass in the parathyroid system, 40 cases more than those in group B
      (40.00%) and 2 cases (2.00%), (p <0.05). There were 10 cases (10.20%) of primary
      hyperparathyroidism in group A and no cases of primary hyperparathyroidism in
      group B (p < 0.05). The occurrence of primary hyperparathyroidism was 26.92%
      (7/26) in the number of cases, with 3 and more cases of urinary calculi, which
      was higher than that in the first recurrent cases (3/72), (p<0.005). CONCLUSIONS:
      One of the key causes of recurrent episodes of urinary calculi is primary
      hyperparathyroidism, which can be applied to high frequency ultrasonography to
      develop professional screening of parathyroid gland in cases of urinary calculi.

PMID- 30229816
TI  - MiRNA-708/CUL4B axis contributes into cell proliferation and apoptosis of
      osteosarcoma.
AB  - OBJECTIVE: The functions of miRNA-708 for various diseases have been confirmed.
      However, its roles in osteosarcoma are unclear. In this study, we aimed to
      explore the role of miRNA-708 in osteosarcoma. PATIENTS AND METHODS: Detection of
      the expression of miRNA-708 and CUL4B was used by quantitative Real Time
      Polymerase Chain Reaction (qRT-PCR). Cells were transfected with miRNA-708 mimics
      (mimics group) and miRNA negative control (NC group). Detection of cell growth
      curve at 24 h, 48 h, 72 h, and 96 h was made by cell counting kit-8 (CCK-8).
      Examination of the apoptosis rate was made by flow cytometry. The identification
      of the regulatory function was made by the luciferase reporter assay. The
      expression level of CUL4B was detected by Western blot. RESULTS: MiRNA-708
      expression was reduced in the tumor cell lines. Compared with NC group, miRNA-708
      expression was up-regulated by transfecting with mimics. Lower proliferation
      efficiency and higher cell apoptosis were showed in miRNA-708 mimics group
      relative to NC group. MiRNA-708 could regulate the expression of CUL4B by binding
      to its 3'UTR area. Furthermore, lower miRNA-708 and higher CUL4B were expressed
      in tumor tissues. MiRNA-708 expression was lower in tissues with IIB-III stage
      than that in IA-IIA stage. CONCLUSIONS: MiRNA-708/CUL4B axis contributes into
      cell proliferation and apoptosis of osteosarcoma.

PMID- 30229817
TI  - MicroRNA-337-5p participates in the development and progression of osteosarcoma
      via ERBB, MAPK and VEGF pathways.
AB  - OBJECTIVE: To investigate the role of microRNA-337-5p in osteosarcoma (OS) and
      its underlying mechanism. PATIENTS AND METHODS: The microRNA (microRNA-337-5p)
      that may be related to OS development was screened out by GEO (Gene Expression
      Omnibus) database. Survival analysis and ROC curve were performed according to
      microRNA-337-5p expressions in OA patients. Besides, the correlation between
      microRNA-337-5p expression and clinical parameters was evaluated by Chi-square
      analysis. Cox regression analysis was performed to detect the relationship
      between the overall survival and clinical parameters of OA patients.
      Subsequently, enriched functions and pathways of microRNA-337-5p were predicted
      by GESA (gene enrichment sets analysis). MicroRNA-337-5p expression was detected
      in 65 OS tissue samples and 30 normal tissue samples by qRT-PCR (quantitative
      Real-Time Polymerase Chain Reaction). For in vitro experiments, after microRNA
      337-5p mimics or microRNA-337-5p inhibitor was transfected into OS cells,
      proliferative and invasive abilities were detected by CCK-8 (Cell Counting Kit-8)
      and transwell assay, respectively. Finally, Western blot was used to explore the
      underlying mechanism of microRNA-337-5p in regulating OS. RESULTS: MicroRNA-337
      5p was overexpressed in serum and tissue samples of OS patients, which was
      valuable in diagnosing OS. Besides, microRNA-337-5p expression was correlated
      with the overall survival and necrosis range of OA patients, whereas not
      correlated with age and sex. GESA indicated that microRNA-337-5p was enriched in
      ERBB, MAPK, and VEGF pathways. In vitro experiments indicated elevated
      proliferative and invasive abilities in MG63 and U2OS cells after microRNA-337-5p
      overexpression. Furthermore, increased expressions of ERBB2, Erk1/2, and VEGF121
      were observed in OS cells after microRNA-337-5p overexpression. CONCLUSIONS:
      MicroRNA-337-5p is upregulated in OS tissues, which is an independent prognostic
      factor in OS. Overexpressed microRNA-337-5p can promote proliferative and
      invasive abilities of OS cells via activating ERBB, MAPK, and VEGF pathways.

PMID- 30229818
TI  - UPK1B promotes the invasion and metastasis of bladder cancer via regulating the
      Wnt/beta-catenin pathway.
AB  - OBJECTIVE: The aim of this study was to investigate the expression of UPK1B in
      bladder cancer (BCa), and to further explore the correlation between UPK1B
      expression and pathological parameters as well as the prognosis of BCa. PATIENTS
      AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used
      to detect the expression of UPK1B in 92 pairs of BCa tissues and adjacent normal
      tissues. The relationship between UPK1B expression and pathological features as
      well as the prognosis of BCa patients was further analyzed. For in vitro
      experiments, the mRNA expression level of UPK1B in BCa cell lines (EJ and T-24)
      was detected by qRT-PCR. In addition, knockdown of UPK1B in BCa cells was
      constructed using small interfering RNA. Effects of UPK1B knockdown on biological
      functions of BCa cells were analyzed by Cell Counting Kit-8 (CCK-8), colony
      formation assay and transwell assay, respectively. Furthermore, the underlying
      mechanism of UPK1B in regulating BCa was evaluated by Western blot and qRT-PCR,
      respectively. RESULTS: The expression of UPK1B in BCa tissues was remarkably
      higher than that of adjacent normal tissues (p<0.05). Compared with BCa patients
      with lower UPK1B expression, those with higher UPK1B expression exhibited higher
      tumor stage, lymph node metastasis and distant metastasis. In vitro experiments
      indicated that cell proliferation, invasion and metastasis were remarkably
      decreased in cells transfected with si-UPK1B when compared with those transfected
      with negative controls. Western blot showed that the expression of key proteins
      in the Wnt/beta-catenin signaling pathway in cells transfected with si-UPK1B was
      significantly down-regulated compared with those transfected with negative
      controls, including beta-catenin, c-myc and cyclinD1. In addition, rescue
      experiments found that UPK1B was regulated by beta-catenin. CONCLUSIONS: UPK1B is
      upregulated in BCa, and is significantly correlated with tumor stage, lymph node
      metastasis, distant metastasis and poor prognosis of BCa. Moreover, UPK1B
      promotes the proliferation, invasion and migration of BCa via regulating the
      Wnt/beta-catenin signaling pathway.

PMID- 30229819
TI  - Desmoglein-2 overexpression predicts poor prognosis in hepatocellular carcinoma
      patients.
AB  - OBJECTIVE: Desmoglein-2 (Dsg2) plays a crucial role in the assembly and adhesion
      of desmosomes. The absent or aberrant expression of Dsg2 was reported to be
      associated with the progression of varies human cancers. However, the expression
      of Dsg2 in hepatocellular carcinoma (HCC) and its association with tumor
      prognosis is still unknown. The aim of this study was to evaluate the expression
      level of Dsg2 in HCC and of the correlation between Dsg2 expression and
      clinicopathological variables. PATIENTS AND METHODS: A total of 104 patients
      diagnosed with HCC were enrolled in this study. Real time-quantitative PCR (RT
      qPCR) and Western blot were performed to determine the expression level of Dsg2
      in HCC tumor tissues and matched noncancerous tissues. Cell proliferation and
      cell cycle were measured by cell counting kit-8 (CCK-8) assay and flow-cytometry
      assay, respectively. RESULTS: Our results revealed that Dsg2 expression was
      significantly higher in HCC tumor tissues than in matched noncancerous tissues (p
      < 0.01), positively correlated with tumor size (p = 0.035) and tumor stage (p =
      0.021). Univariate and multivariate analyses demonstrated Dsg2 expression was an
      independent prognostic factor for overall survival. Meanwhile, we found knockdown
      the expression of Dsg2 using small interfering RNA (siRNA) could efficiently
      impaired HCC cell proliferation rate and cell cycle progression (p < 0.05).
      CONCLUSIONS: Taken together, our results suggest that increased Dsg2 expression
      was associated with tumor progression in HCC and may function as a promising
      biomarker for unfavorable prognosis of HCC.

PMID- 30229820
TI  - The increase of miR-27a affects the role of cisplatin on proliferation and
      migration capacities of liver cancer cells.
AB  - OBJECTIVE: To study the effects of chronic virus-mediated micro ribonucleic acid
      miR-27a on proliferation and migration capacities of liver cancer cells. PATIENTS
      AND METHODS: A total of 60 patients with primary liver cancer from January 2015
      to December 2016 were selected as observation group, 60 patients with chronic
      liver disease were selected as control group, and another 60 healthy subjects who
      received physical examination during the same period were selected as healthy
      group. All patients received serum miRNA detection. The different expressions of
      serum miRNAs in healthy people, patients with chronic liver disease, and patients
      with liver cancer were analyzed. The correlations of miR-27a with growth and
      proliferation of liver cancer MCC-7721 cells were studied. RESULTS: The levels of
      miR-27a and miR-664b in subjects in control group and healthy group were
      significantly lower than those in observation group, but the expression levels of
      miR-30a were statistically elevated (p<0.05). The expression of serum miR-27a in
      liver cancer patients with higher tumor-node-metastasis (TNM) staging (stage III
      IV, number of tumors >1, tumor size >5 cm, and vascular invasion) was
      significantly higher than those in patients with lower TNM staging (stage I-II,
      number of tumors =1, tumor size <=5 cm, and no vascular invasion) (p<0.05). At 48
      h and 72 h after transfection, the proliferation of liver cancer MCC-7721 cells
      was significantly enhanced compared to that in non-transfection group (p<0.05).
      The level of miR-27a was significantly upregulated in cisplatin-resistant liver
      cancer A549/CDDP cells compared with that in parental A549 cells. MiR-27a
      regulated epithelial-mesenchymal transition (EMT) and cisplatin resistance in
      vitro, while modulated the in vivo response of liver cancer cells to cisplatin.
      Further studies identified the Raf kinase inhibitor protein (RKIP) as a direct
      and functional target of miR-27a. The knockdown of RKIP by RNAi showed a similar
      effect to ectopic miR-27a expression, whereas the over-expression of RKIP
      weakened the function of miR-27a in liver cancer cells. CONCLUSIONS: MiR-27a
      participated in the proliferation and migration capacities of liver cancer cells
      and influenced the effect of cisplatin via targeting RKIP. The high expression of
      miR-27a is closely related to the malignant degree of liver cancer, which
      provides guidance for the diagnosis, targeted therapy, and prognostic evaluation
      of liver cancer.

PMID- 30229821
TI  - Down-regulation of miR-29a facilitates apoptosis of colorectal carcinoma cell
      SW480 and suppresses its Paclitaxel resistance.
AB  - OBJECTIVE: PTEN can suppress PI3K/AKT activity, and regulate cell proliferation,
      apoptosis, and drug resistance. The previous study showed that up-regulation of
      miR-29a played an essential role in the occurrence of colorectal carcinoma. This
      study aimed to investigate the role and related mechanism of miR-29a in mediating
      Paclitaxel sensitivity of colorectal carcinoma cells. MATERIALS AND METHODS:
      Bioinformatics analysis was performed to study the existence of binding sites
      between miR-29a and targeting gene mRNA. Dual luciferase reporter assay was
      conducted to validate the targeted regulation. The expressions were compared
      between CCD841 CoN cells, colorectal carcinoma cell line SW480, and drug
      resistant cell line SW480/Paclitaxel. Cell apoptosis and proliferation were
      measured by flow cytometry. In vitro cultured SW480/Paclitaxel cells were
      transfected with miR-29a or pcDNA3.1-PTEN. MiR-29a and PTEN expressions were
      measured by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT
      PCR) and Western blot, followed by flow cytometry on the detection of cell
      apoptosis as well as proliferation assay. RESULTS: A targeted regulatory
      relationship existed between miR-29a and PTEN. Comparing to CCD841 CoN cells,
      high level of miR-29a and decreasing expression of PTEN were found in SW480
      cells. Moreover, further higher miR-29a and lower PTEN expressions were observed
      in SW480/Paclitaxel cells. Paclitaxel remarkably inhibited proliferation and
      facilitated apoptosis of SW480 cells but not SW480/Paclitaxel cells. Transfection
      of miR-29a inhibitor or pcDNA3.1-PTEN remarkably elevated PTEN expression,
      suppressed p-AKT expression, weakened proliferation, and enhanced apoptosis of
      SW480/Paclitaxel cells. CONCLUSIONS: Our data demonstrated that suppression of
      miR-29a enhanced PTEN expression, inhibited cancer cell proliferation,
      facilitated apoptosis, and weakened drug resistance, which provides academic
      basis for the treatment of colorectal cancer.

PMID- 30229822
TI  - The clinical observation of verapamil in combination with interventional
      chemotherapy in advanced gastric cancer.
AB  - OBJECTIVE: We analyzed the clinical observations of target arterial infusion of
      verapamil combined with chemotherapy as therapy for advanced gastric cancer.
      PATIENTS AND METHODS: From March 2012 to December 2015, a total of 63 patients
      with advanced gastric cancer were admitted to our department. The target artery
      in the control group was perfused with chemotherapy drugs only, and the target
      artery in the therapy group was injected with verapamil combined with
      chemotherapy drugs. RESULTS: The therapeutic effect of the therapy group was
      significantly better than that of the control group in the primary foci of
      gastric cancer. Liver metastatic lesions: 11 patients in the control group had
      liver metastases and 25 patients in the therapy group had liver metastases. The
      effective rate (CR+PR) of the therapy group was significantly better than the
      control group. Clinical benefit evaluation: in the therapy group of 43 cases, 40
      cases presented positive clinical benefit and 38 cases positive clinical weight
      in KFS scoring system; the clinical benefit of the therapy group was
      significantly better than control group. Survival analysis: the disease
      progression-free rate and survival rate of the therapy group were 12 months and
      24 months, which were higher than those in the control group. The median PFS and
      median OS were also significantly longer than those in the control group
      (p<0.01). In the therapy group, adverse effects of chemotherapy in 43 patients
      were relieved in a short time. CONCLUSIONS: Target arterial infusion of verapamil
      combined with chemotherapy drugs for advanced gastric cancer can significantly
      improve the efficacy of chemotherapy drugs and prolong the survival of patients.

PMID- 30229823
TI  - The SNORA21 expression is upregulated and acts as a novel independent indicator
      in human gastric cancer prognosis.
AB  - OBJECTIVE: Emerging evidence indicates that small nucleolar RNAs (snoRNAs) act
      crucial roles in oncogenesis. Herein, the aim of this study is to investigate the
      clinical value of SNORA21 expression in gastric cancer (GC). PATIENTS AND
      METHODS: The expression of SNORA21 was determined in 79 cases of GC tissues and
      adjacent normal tissues by quantitative Real-Time Polymerase Chain Reaction (qRT
      PCR) analysis. The association between SNORA21 expression and clinicopathological
      features was analyzed by the chi-square test. The survival curves were calculated
      by the Kaplan-Meier method and log-rank test. Univariate and multivariate
      analyses were used to assess the prognostic value of SNORA21 expression. RESULTS:
      Our results first demonstrated that SNORA21 expression was significantly
      upregulated in human GC tissues and cells compared to their corresponding
      adjacent normal tissues and GES-1 cells, respectively (p<0.05). Furthermore,
      elevated SNORA21 expression was significantly associated with distant metastasis
      (p<0.05) and lymph node metastasis (p<0.05) in GC patients. Kaplan-Meier survival
      plots demonstrated that higher SNORA21 expression was associated with poor
      disease-free survival (DFS) and overall survival (OS) rate, respectively.
      Univariate analysis and multivariate regression analysis indicated that a higher
      SNORA21 was an independent risk factor for prognosis in GC patients. CONCLUSIONS:
      The current results indicate that SNORA21 expression may be served as a predictor
      of GC prognosis.

PMID- 30229824
TI  - Expression of miR-1294 is downregulated and predicts a poor prognosis in gastric
      cancer.
AB  - OBJECTIVE: MicroRNAs (miRNAs) play critical roles in regulating tumor development
      and progression. The aim of the study is to investigate the clinical significance
      of miR-1294 expression in gastric cancer (GC). PATIENTS AND METHODS: The
      expression of miR-1294 in 82 cases of GC tissues and adjacent normal tissues was
      determined using quantitative Real Time-PCR (qRT-PCR) analyses. Survival plot was
      calculated using the Kaplan-Meier methods and log-rank test from the date of
      operation to the time of death or last follow-up date. The association between
      miR-1294 expression and clinical categorical data was analyzed using the chi
      squared test. Moreover, Univariate and multivariate Cox analysis were performed
      to assess the risk factors of GC prognosis. RESULTS: We showed that miR-1294
      expression was significantly downregulated in GC tissues compared to adjacent
      normal tissues. The low expression of miR-1294 in patients with GC was correlated
      with clinicopathological parameters including larger tumor size, lymph node
      metastasis, and distant metastasis. Kaplan-Meier survival analysis showed that GC
      patients with lower miR-1294 expression exhibited a shorter disease-free survival
      (DFS) and overall survival (OS) time compared to those patients with higher miR
      1294 expression. Multivariate Cox analysis showed that lower miR-1294 expression,
      tumor size, lymph node metastasis, and distant metastasis were identified as
      independent risk factors of GC prognosis. CONCLUSIONS: Our results provided
      evidence that miR-1294 expression was significantly downregulated in GC and may
      serve as a predictor of GC prognosis.

PMID- 30229825
TI  - Study on molecular mechanism of MiRNA-29a in promoting proliferation and invasion
      of non-small-cell lung cancer by inhibiting MTSS1.
AB  - OBJECTIVE: To investigate the biological role of micro-ribonucleic acid (miR)-29a
      in non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: 55 cases of NSCLC
      tissue specimens and paired normal lung tissue specimens collected in the
      Department II of Oncology, Ruikang Hospital Affiliated to Guangxi University of
      Chinese Medicine from July 2012 to April 2015 were randomly included. The
      fluorescent quantitative polymerase chain reaction, Western blotting, and
      immunohistochemistry were performed to detect the expression levels of miR-29a
      and metastasis suppressor 1 (MTSS1). Pearson correlation analysis was utilized to
      investigate the relationship between miR-29a expression and MTSS1 expression in
      NSCLC tissues, and the Kaplan-Meier survival curves were constructed to analyze
      the association of miR-29a expression with the survival time of NSCLC patients.
      A54 proliferation and invasion abilities were measured by means of plate clone
      formation assay, and transwell assay after the miR-29a was suppressed by miRNA
      inhibitor. Luciferase assay was used to detect the target gene of miR-29a.
      RESULTS: In NSCLC tissues, the miR-29a expression level was higher than that in
      normal lung tissues (p<0.05), while the expression level of MTSS1 protein was
      remarkably lower than that in normal lung tissues (p<0.05). The median survival
      time of the patients was 15.1 months in high miR-29a expression group and 18.3
      months in low miR-29a expression group (p<0.05). The miR-29a expression was
      negatively correlated with the expression level of MTSS1 protein in NSCLC tissues
      (r=-0.762, p<0.05). Luciferase results suggest that miR-29a binds to the promoter
      region of MTSS1 and inhibits its transcription level. The expression of MTSS1
      protein was up-regulated notably after miR-29a knockdown by an inhibitor. It was
      revealed in the results of transwell assay and plate clone formation assay that
      the proliferative and invasive capacity of A549 cells was significantly decreased
      after knockdown of miR-29a. CONCLUSIONS: The transcribed miR-29a down-regulates
      the protein level of MTSS1, suppressor of tumor proliferation and invasion,
      thereby promoting the proliferative and invasive capacity of NSCLC cells. Both
      miR-29a and MTSS1 are expected to become potential therapeutic targets for NSCLC.

PMID- 30229826
TI  - Correlations between the expression of C-erB-2, CD34 and ER in breast cancer
      patients and the signs of conventional ultrasonography and ultrasound
      elastography.
AB  - OBJECTIVE: This study aims to investigate the correlations between the expression
      of human epidermal growth factor receptor 2 (C-erB-2), CD34, and estrogen
      receptor (ER) in breast cancer (BC) patients, and the signs of conventional
      ultrasonography and ultrasound elastography. PATIENTS AND METHODS: Clinical data
      of 88 patients who were pathologically diagnosed as breast cancer were
      retrospectively analyzed. HI VISION Avius color ultrasound device was used to
      perform ultrasound and related ultrasound parameters were analyzed. Expressions
      of C-erB-2, CD34, and ER were detected by immunohistochemistry. RESULTS: There
      was a correlation between positive expression of C-erB-2 and the blood supply,
      lymph node metastasis and microcalcification in patients (p < 0.05). Patients
      were divided into high expression group and low expression group according to the
      median expression level of CD34. Expression of CD34 was correlated with the
      ultrasound sign of lymph node metastasis (p < 0.05). Positive expression of ER
      was correlated with the morphology, margin, and perimeter of the tumor (p <
      0.05). Expression levels of C-erB-2, CD34, and ER were found to be increased in
      BC patients. CONCLUSIONS: Combination of upregulated expression of C-erB-2, CD34,
      and ER and signs of ultrasound can improve the diagnosis of BC.

PMID- 30229827
TI  - MiR-411-5p acts as a tumor suppressor in non-small cell lung cancer through
      targeting PUM1.
AB  - OBJECTIVE: The aim of this study was to investigate the expression of micro
      ribonucleic acid-411-5P (miR-411-5p) in non-small cell lung cancer (NSCLC), and
      to explore the effect of miR-411-5p on the biological behavior of NSCLC cells as
      well as the underlying molecular mechanism. PATIENTS AND METHODS: Quantitative
      Real Time- Polymerase Chain Reaction (qRT-PCR) was used to detect the expression
      level of miR-411-5p in NSCLC tissues and cells. MiR-411-5p mimics and relevant
      controls were transfected into NSCLC cells according to the instructions of
      Lipidosome 2000. Transfected cells were divided into the experimental group and
      the control group. The transfection efficiency of each group was detected by qRT
      PCR. After miR-411-5p overexpression, methyl thiazolyl tetrazolium (MTT) assay,
      flow cytometry, and transwell assay were used to detect the biological changes of
      cells in each group. Bioinformatics predicted that pumilio homolog 1 (PUM1) was
      the target gene of miR-411-5p. Subsequently, the mRNA and protein expression
      level of PUM1 in each group was detected by qRT-PCR and Western blotting,
      respectively. Dual-luciferase reporter assay was used to validate the target
      regulatory relationship between miR-411-5p and PUM1. RESULTS: The results of qRT
      PCR showed that miR-411-5p was relatively lowly expressed in NSCLC tissues and
      cells. After miR-411-5p overexpression, MTT results revealed that the
      proliferation of NSCLC cells was decreased. Flow cytometry results indicated that
      the apoptosis rate of NSCLC cells was increased, and cell cycle was arrested in
      the G0-G1 phase. Meanwhile, the transwell assay demonstrated that the migration
      and invasion abilities of NSCLC cells were decreased. Bioinformatics predicted
      that PUM1 was the target gene of miR-411-5p. After miR-411-4p was overexpressed
      in NSCLC cells, qRT-PCR and Western blotting showed that both the mRNA and
      protein expression levels of PUM1 were up-regulated. Moreover, dual-luciferase
      reporter assay demonstrated that miR-411-5p could significantly inhibit the
      luciferase activity of wild-type PUM1-3'-untranslated region (3'-UTR). However,
      it exhibited no effect on the luciferase activity of cells transfected with
      mutant plasmids. CONCLUSIONS: MiR-411-5p may be involved in regulating the
      biological function of NSCLC cells via targeting PUM1. In addition, miR-411-5p
      may serve as a potential target for the molecular therapy of NSCLC.

PMID- 30229828
TI  - MiR-451a suppressed cell migration and invasion in non-small cell lung cancer
      through targeting ATF2.
AB  - OBJECTIVE: To explore the role of miR-451a in the migration and invasion of non
      small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: Quantitative Real
      time-polymerase chain reaction (qRT-PCR) and Western blot were performed to
      detect the levels of miR-451a and activating transcription factor 2 (ATF2) in
      NSCLC. Transwell assay was employed to analyze the migratory and invasive
      abilities in NSCLC cells. Dual-luciferase reporter assay was applied to confirm
      the binding condition of miR-451 and its target gene in NSCLC cells. RESULTS: MiR
      451a was downregulated in NSCLC tissues and lung cancer cell lines A549 and NCI
      H460, while ATF2 was upregulated. The mRNA level of miR-451a was negatively
      correlated to ATF2. Additionally, miR-451a regulated cell migration and invasion
      through targeting ATF2. Furthermore, ATF2 could reverse the inhibitory migration
      and invasion of A549 cells induced by miR-451a. CONCLUSIONS: MiR-451a inhibits
      the migratory and invasive abilities of NSCLC cells through ATF2 regulation. The
      newly identified miR-451a/ATF2 axis provides a novel insight into the
      pathogenesis ofNSCLC.

PMID- 30229829
TI  - MicroRNA-791 is an independent prognostic factor of papillary thyroid carcinoma
      and inhibits the proliferation of PTC cells.
AB  - OBJECTIVE: To investigate the significance and possible mechanism of miR-791 in
      the pathogenesis of papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: The
      expression of miR-791 in 80 cases of thyroid carcinoma tissues and 80 cases of
      paracancerous tissues was detected by quantitative Real-time-polymerase chain
      reaction (qRT-PCR). After miR-791 mimics were transfected into thyroid cancer
      cells by liposome method, the cell proliferation was detected by Cell Counting
      Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EDU), respectively. Cell cycle was
      detected by flow cytometry. RESULTS: The expression of miR-791 in thyroid cancer
      tissue was significantly lower than that of normal thyroid. The mir-719
      expression is positively correlated with the prognosis of thyroid carcinoma.
      After transfection of miR-791 mimics, the proliferation ability of TPC-1 and
      HTH83 cells was weakened, and the cell cycle was blocked in the G0/G1 phase.
      Further study on the underlying mechanism found that after overexpression of miR
      791, the expressions of Cyclin D1, CKD6 and CDK4 decreased significantly, while
      the expression of cyclin inhibitor P21 increased significantly. CONCLUSIONS: MiR
      791 is lowly expressed in thyroid cancer. MiR-791 may inhibit thyroid cancer cell
      proliferation by blocking thyroid cancer cells in G0/G1 phase, thus participating
      in the impediment of thyroid cancer development.

PMID- 30229830
TI  - MicroRNA-138 inhibits proliferation and induces apoptosis of laryngeal carcinoma
      via targeting MAPK6.
AB  - OBJECTIVE: To explore whether microRNA-138 could regulate the incidence and
      progression of laryngeal carcinoma through modulating proliferation and apoptosis
      of laryngeal carcinoma cells via MAPK6. PATIENTS AND METHODS: MicroRNA-138
      expression in laryngeal carcinoma tissues and paracancerous tissues were detected
      by qRT-PCR (Quantitative Real-Time Polymerase Chain Reaction). The regulatory
      effects of microRNA-138 on proliferation and apoptosis of laryngeal carcinoma
      cells were detected by colony formation assay and flow cytometry, respectively.
      Target gene of microRNA-138 was predicted by online software and verified by
      luciferase reporter gene assay. Corresponding plasmids of microRNA-138 and the
      target gene were constructed. Rescue experiments were conducted to explore the
      regulatory effect of microRNA-138 on the target gene. RESULTS: MicroRNA-138 was
      downregulated in laryngeal carcinoma tissues than that of paracancerous tissues.
      MicroRNA-138 knockdown resulted in increased proliferation and decreased
      apoptosis of laryngeal carcinoma cells. MAPK6 was predicted as the target gene of
      microRNA-138. Luciferase reporter gene assay further verified that MAPK6 could
      directly bind to microRNA-138. Both mRNA and protein levels of MAPK6 were
      downregulated after microRNA-13 overexpression in laryngeal carcinoma cells.
      Rescue experiment results indicated that increased proliferation and decreased
      apoptosis of laryngeal carcinoma cells resulted from microRNA-13 knockdown were
      partially reversed by MAPK6 overexpression. CONCLUSIONS: MicroRNA-138 is
      downregulated in laryngeal carcinoma patients. MicroRNA-138 knockdown promotes
      proliferation and inhibits apoptosis of laryngeal carcinoma cells via inhibiting
      MAPK6 expression.

PMID- 30229831
TI  - UCA1 promotes papillary thyroid carcinoma development by stimulating cell
      proliferation via Wnt pathway.
AB  - OBJECTIVE: To explore whether lncRNA UCA1 (long non-coding RNA urothelial
      carcinoma associated 1) could promote the development of papillary thyroid
      carcinoma (PTC) via Wnt pathway and its underlying mechanism. PATIENTS AND
      METHODS: UCA1 expression in PTC tissues, paracancerous tissues, and thyroid
      cancer cells were detected by quantitative Real Time-Polymerase Chain Reaction
      (qRT-PCR). UCA1 lentivirus was then constructed for the following in vitro
      experiments. Proliferative ability of MTC and SW579 cells was detected by cell
      counting kit-8 (CCK-8) and colony formation assay. Cell apoptosis after altering
      UCA1 expression in MTC and SW579 cells was detected by flow cytometry and Western
      blot. Invasive ability of MTC and SW579 cells was detected by transwell and wound
      healing assay. Finally, protein expressions of Wnt pathway-related genes were
      detected by Western blot. RESULTS: UCA1 was overexpressed in PTC tissues and
      thyroid cancer cells. UCA1 expression was positively correlated to tumor size,
      tumor stage, and metastasis of PTC. Overexpressed UCA1 promoted proliferation and
      invasion, whereas inhibited apoptosis of thyroid cancer cells via Wnt pathway.
      CONCLUSIONS: Overexpressed UCA1 promotes PTC development by stimulating
      proliferation, migration, and anti-apoptosis of thyroid cancer cells via
      activating Wnt pathway.

PMID- 30229832
TI  - Polymorphisms in lncRNA PTENP1 and the risk of oral squamous cell carcinoma in a
      Chinese population.
AB  - OBJECTIVE: PTENP1, a long noncoding RNA, has previously been reported to be
      involved in tumorigenesis and cancer progression. The relationship between PTENP1
      and susceptibility tumors is reported, while, an association of PTENP1 with the
      risk of oral squamous cell carcinoma (OSCC) in Chinese population is lacked. This
      research is designed to investigate the association of PTENP1 with susceptibility
      of OSCC. PATIENTS AND METHODS: In this research, TaqMan technology was used to
      test genotype in 342 OSCC patients and 711 healthy controls, so as to analyze the
      association between PTENP1 polymorphisms (rs7853346 rs865005 and rs10971638) and
      susceptibility of oral squamous cell carcinoma. RESULTS: The results of this
      research showed that rs7853346 [Additive model: Adjusted odds ratio (OR) = 0.81,
      95% confidence interval (CI) = 0.66-0.99] was related to the OSCC risk. It was
      not found that the other two sites were associated with the susceptibility of
      OSCC. CONCLUSIONS: This research indicated that rs7853346 is statistically
      correlated with the OSCC risk.

PMID- 30229833
TI  - Suppressed CCL2 expression inhibits the proliferation of leukemia cells via the
      cell cycle protein Cyclin D1: preliminary in vitro data.
AB  - OBJECTIVE: Chemokine (C-C motif) ligand 2 (CCL2) is a member of the CC subfamily,
      which displays chemotactic activity for monocytes and basophils. This molecule
      plays a very important role in many solid tumors and shows changes in the bone
      marrow microenvironment. However, its role in acute myeloid leukaemia (AML) is
      still unclear. MATERIALS AND METHODS: In this study, we established a HL-60 cell
      line with CCL2 knockdown to explore its effect on leukemogenesis. Lentivirus with
      CCL2-knockdown was successfully constructed after screening effective CCL2 short
      hairpin RNA (shRNA) sequences and was transfected into HL-60 cells, which was
      further validated at the mRNA and protein levels by real-time polymerase chain
      reaction (PCR) and Western blotting, respectively. RESULTS: Low expression of
      CCL2 significantly decreased HL-60 cell growth by increasing the cell arrest at
      G1 phase by 12% more than controls. We applied RNA sequencing technology to
      discriminate the gene expression profiles between the cells with CCL2 knockdown
      and the controls, and Cyclin D1 was selected for further experiments as its
      expression level was significantly downregulated, which was validated at the mRNA
      and protein levels. Cyclin D1 knockdown experiments showed that the cell
      proliferation rate was evidently decelerated, and cell cycle analysis also
      indicated a similar pattern for CCL2. CONCLUSIONS: Our study revealed that Cyclin
      D1 is an effector that mediates CCL2's function in cell proliferation by blocking
      cells at G1 phase.

PMID- 30229834
TI  - MiR-7 alleviates secondary inflammatory response of microglia caused by cerebral
      hemorrhage through inhibiting TLR4 expression.
AB  - OBJECTIVE: This study was conducted to analyze the effect of miR-7 on the
      inflammatory response of microglia in vitro and in vivo by constructing an
      intracerebral hemorrhage model. PATIENTS AND METHODS: In this study, we first
      established a model of cerebral hemorrhage in rat for in vivo experiments, and
      used lipoprotein (LPS) to induce an inflammatory response development in
      microglial cells, and constructed microglial inflammation models for in vitro
      experiments. Quantitative Real-time-polymerase chain reaction (qRT-PCR) was used
      to detect the expression of miR-7 in the rat model of cerebral hemorrhage and
      microglia with inflammation. The effect of miR-7 on the inflammation caused by
      intracerebral hemorrhage was evaluated through measuring the expression of IL
      1beta, IL-8 and TNF-alpha by enzyme-linked immunosorbent assay (ELISA). Dual
      luciferase reporter assay was used to detect the binding site of miR-7 to TLR4.
      Western blot was used to evaluate the level of TLR4 after overexpression and
      knockdown of miR-7 and to evaluate whether miR-7 alleviated the secondary
      inflammatory response of microglia after cerebral hemorrhage by inhibiting the
      expression of TLR4. RESULTS: The expression of miR-7 in the rat cerebral
      hemorrhage model and microglial inflammation model tissue was significantly lower
      than that in the normal control group. Expression of inflammatory cytokines
      including IL-1beta, IL-8 and TNF-alpha was significantly increased in rats with
      intracerebral hemorrhage and microglial inflammation in rats, and the expression
      of these inflammatory cytokines was partially reversed after overexpression of
      miR-7. Double luciferase reporter gene and ELISA results showed that miR-7 could
      inhibit the expression of TLR4 and relieve the secondary inflammatory response of
      microglia after cerebral hemorrhage. CONCLUSIONS: We demonstrated that, in in
      vivo and in vitro experiments, miR-7 could reduce the LPS-induced inflammatory
      response produced by microglial cells, and alleviate the inflammation in the
      brain of rats with cerebral hemorrhage.

PMID- 30229835
TI  - MicroRNA-544 inhibits inflammatory response and cell apoptosis after cerebral
      ischemia reperfusion by targeting IRAK4.
AB  - OBJECTIVE: Stroke remains the most common malignant cerebrovascular event in the
      world. The correlation between the expression of miR-544 and the degree of
      cerebral ischemia reperfusion (CIR) injury has not been well recognized in recent
      years. This study focuses on the effect of miR-544 on inflammation and apoptosis
      after CIR. PATIENTS AND METHODS: Plasma expression of miR-544 in ischemic stroke
      (IS) patients and healthy controls was determined by quantitative reverse
      transcriptase-polymerase chain reaction (qRT-PCR). The effects of miR-544 on
      cerebral infarction and neurological deficits were verified in vitro by tail vein
      injection of Ago-miR-544. Western blotting was utilized to examine protein
      expressions of key proteins involving in inflammation and apoptosis in mouse
      brain. Western blotting, immunofluorescence staining and luciferase assays were
      used to demonstrate whether miR-544 influences the expression of interleukin-1
      receptor-associated kinase 4 (IRAK4), downstream inflammatory and apoptosis
      related proteins. RESULTS: MiR-544 was found decreased in peripheral blood of IS
      patients compared with healthy controls. MiR-544 has been shown to relieve
      neurological deficits and reduce the volume of cerebral infarction in mice.
      Overexpression of miR-544 ameliorated the inflammation and apoptotic responses in
      brain tissue after ischemia reperfusion by down-regulating the expression of
      IRAK4, whereas the low expression was opposite in vivo and in vitro. CONCLUSIONS:
      We found that miR-544 may participate in controlling inflammation and apoptosis
      after ischemia-reperfusion by targeting IRAK4, providing possible diagnostic
      indicators and therapeutic targets for IS.

PMID- 30229836
TI  - IL-10 targets Th1/Th2 balance in vascular dementia.
AB  - OBJECTIVE: The pathogenesis of vascular dementia (VD) is not fully elucidated.
      Th1/Th2 balance may change in VD, leading to numerous inflammatory cytokines
      secretion. Interleukin-10 (IL-10) is an immune suppressor, while its function in
      VD and correlation with Th1/Th2 balance are still unclear. MATERIALS AND METHODS:
      The healthy male rats were randomly divided into three groups, including sham
      group, model group, and IL-10 group. Th1 and Th2 cytokines IL-2, IL-4, IL-6, and
      tumor necrosis factor-alpha (TNF-alpha) expressions in the serum were tested by
      enzyme-linked immunosorbent assay (ELISA). IL-10 expression in brain tissue and
      peripheral blood was detected by Real-Time PCR and ELISA. The correlation
      relationship between IL-10 and T helper cells 1/2 (Th1/Th2) cytokines was
      analyzed. Hippocampus cell apoptosis was determined by caspase 3 activity kit.
      Nuclear transcription factor 2 kappaB (NF-kappaB) expression was evaluated by
      Western blot. RESULTS: IL-10 levels were decreased, caspase 3 activity was
      enhanced, NF-kappaB expression was declined, IL-2 and TNF-alpha secretion were up
      regulated, while IL-4 and IL-6 secretion were reduced in hippocampus tissue and
      peripheral blood from VD model rat compared to sham group (p<0.05). IL-10
      significantly attenuated caspase 3 activity, up-regulated NF-kappaB expression,
      reduced IL-2 and TNF-alpha secretion, and enhanced IL-4 and IL-6 secretion
      (p<0.05). IL-10 was negatively correlated with Th1 cytokines and positively
      correlated with Th2 cytokines (p<0.05). CONCLUSIONS: IL-10 expression declined in
      VD and participated in regulating Th1/Th2 balance. IL-10 participated in VD
      incidence and development through regulating cell apoptosis and NF-kappaB
      expression.

PMID- 30229837
TI  - MicroRNA-218 alleviates sepsis inflammation by negatively regulating VOPP1 via
      JAK/STAT pathway.
AB  - OBJECTIVE: To investigate the possible role of microRNA-218 in the pathogenesis
      of sepsis and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-218
      expression in peripheral blood mononuclear cells (PBMCs) of 53 sepsis patients
      and 20 healthy controls was detected by quantitative Real-Time Polymerase Chain
      Reaction (qRT-PCR). MicroRNA-218 expression in Treg cells of sepsis patients and
      healthy controls was also detected. The binding condition of microRNA-218 to
      VOPP1 was confirmed by dual-luciferase reporter gene assay and RNA binding
      protein immunoprecipitation (RIP) assay, respectively. Furthermore, sepsis mouse
      model was constructed. MicroRNA-218 mimics or inhibitor was injected into mouse
      tail vein, respectively. The proportion of Treg cells was compared between sepsis
      mice injected with microRNA-218 mimics and inhibitor. Expressions of microRNA-218
      and VOPP1 in Treg cells extracted from sepsis mouse were detected. ELISA (enzyme
      linked immunosorbent assay) assay was conducted to detect serum levels of
      inflammatory factors (TNF-alpha, IL-6, TGF-beta, and IL-10) in sepsis mouse.
      Finally, protein expressions of key genes in JAK/STAT pathway in sepsis mouse
      spleen were detected by Western blot. RESULTS: MicroRNA-218 expression in sepsis
      patients was remarkably lower than that of healthy controls, which was gradually
      decreased with the deteriorating symptoms. Specifically, microRNA-218 expression
      was the lowest in patients who died of sepsis. Downregulated microRNA-218 was
      seen in Treg cells extracted from advanced sepsis patients. Both dual-luciferase
      reporter gene assay and RIP assay suggested that microRNA-218 can bind to VOPP1.
      VOPP1 expression was negatively regulated by microRNA-218. In advanced sepsis
      mouse, administration of microRNA-218 mimics increased expressions of TNF-alpha
      and IL-6, but decreased expressions of IL-10 and TGF-beta. Western blot results
      indicated that microRNA-218 can inhibit the JAK/STAT pathway in sepsis mice.
      CONCLUSIONS: MicroRNA-218 expression in the PBMCs of sepsis patients was
      remarkably reduced, which inhibited sepsis development via negatively regulating
      VOPP1 and suppressing JAK/STAT pathway.

PMID- 30229838
TI  - Low expression of miR-203 promoted diabetic nephropathy via increasing TLR4.
AB  - OBJECTIVE: To investigate the relationship between microRNA-203 (miR-203) and
      diabetic nephropathy and its potential mechanism. MATERIALS AND METHODS: The
      expression of microRNA-203 in mice with diabetic nephropathy and M4200 cells
      cultured with high glucose was detected by quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR). Toll-like receptor 4 (TLR4), the target gene
      of microRNA-203, was predicted and screened by bioinformatics method. Real-time
      quantitative PCR and Western blot were used to detect the endogenous TLR4 level
      in renal cortex of db/db mice with diabetic nephropathy and glomerular mesangial
      cells cultured in high glucose or low glucose. The expression of microRNA-203 and
      TLR4 mRNA were evaluated by RT-PCR after treatment of miR-203 mimics and
      inhibitor. The protein of TLR4 level was detected by Western blot. Additionally,
      the proliferation ability of cells was evaluated by Cell Counting Kit-8 (CCK8).
      The target relationship between microRNA-203 and TLR4 3' UTR was confirmed by
      luciferase reporter assay RESULTS: The expression of miR-203 was significantly
      decreased in the kidney of mice with diabetic nephropathy and M4200 cells
      cultured in high glucose. On the contrary, TLR4 expression was significantly
      increased. Results of in vitro experiments showed that miR-203 could bind to
      3'UTR region of TLR4. Overexpression of microRNA-203 significantly decreased the
      levels of TLR4 mRNA and protein. Meanwhile, low expression of miR-203 leaded to
      increased TLR4 expression, resulting in an enhanced proliferation of M4200 cells.
      CONCLUSIONS: The downregulation of microRNA-203 leaded to an increased level of
      TLR4, thus promoting proliferation of M4200 cells in the pathogenesis of diabetic
      nephropathy.

PMID- 30229839
TI  - Correlations of 25-hydroxyvitamin D3 level in patients with ulcerative colitis
      with inflammation level, immunity and disease activity.
AB  - OBJECTIVE: To investigate the correlations between 25-hydroxyvitamin D3 (25-OHD3)
      level in patients with ulcerative colitis (UC) and inflammation level, immunity,
      disease activity. PATIENTS AND METHODS: The serum level of 25-OHD3, inflammation
      status, immunity level and disease activity in patients (n=122) with UC in our
      hospital from 2015 to October 2017 were evaluated and analyzed. RESULTS: The
      levels of inflammatory factors [C-reactive protein (CRP) and tumor necrosis
      factor-alpha (TNF-alpha)] in low 25-OHD3 group were higher than those in non-low
      25-OHD3 group (p<0.01 and p<0.05), and both expressions of CRP and TNF-alpha in
      patients presented linearly negative correlations with the level of 25-OHD3
      (r2=0.8351, r2=0.7298). There were no significant differences in the levels of
      immunoglobulin G (IgG) and complement C3 in low 25-OHD3 group compared with those
      in non-low 25-OHD3 group (p>0.05). There was an overall decreasing trend of 25
      OHD3 level as disease activity increased, and there were statistically
      significant differences in the levels of 25-OHD3 in each group in remission
      period and mild, moderate and severe activity periods. The disease activity score
      of patients showed a linearly negative correlation with the level of 25-OHD3
      (r2=0.8465). The level of 25-OHD3 in the observation group (treated with
      mesalazine combined with vitamin D) was increased with the time of medication,
      and the level was higher than that in the control group (treated with mesalazine
      only). CRP, TNF-alpha, and disease activity score in the observation group were
      decreased with the time of medication, and the level was lower than that in the
      control group. CONCLUSIONS: The level of 25-OHD3 in UC patients is linearly
      correlated with the level of inflammation and disease activity. At the same time,
      combined treatment with vitamin D improves the reducing level of inflammation and
      limits the disease activity. Therefore, 25-OHD3 can be used in the assessment of
      the level of inflammation and disease activity, and as a potential tool in the
      treatment.

PMID- 30229840
TI  - Relations of hepatic steatosis with liver functions, inflammations, glucolipid
      metabolism in chronic hepatitis B patients.
AB  - OBJECTIVE: To investigate the relations between the steatosis and liver
      functions, inflammations, and glucolipid metabolism in chronic hepatitis B
      patients. PATIENTS AND METHODS: A total of 144 chronic hepatitis B patients who
      were admitted to our hospital from January 2015 to April 2017 were selected and
      divided into the steatosis group (n=73) and the non-steatosis group (n=71)
      according to the detection of hepatic puncture biopsy. The general information of
      the patients including age, sex, and body mass index (BMI) was collected, and
      patients' liver functions, inflammations, and glucolipid metabolism indicators
      were determined and compared between the chronic hepatitis patients with
      steatosis and without steatosis. The chronic hepatitis patients with steatosis
      were further divided into the normal group and the abnormal group based on the
      level of C-reactive protein (CRP) (8 mg/L). Besides, according to the level of
      aspartate aminotransferase (AST), these patients were divided into the normal
      liver function group (AST<40 U/L) and the abnormal liver function group (AST>40
      U/L), among whom the hepatic steatosis, glucolipid metabolism, and inflammations
      were compared. At the same time, the chronic hepatitis B patients with steatosis
      were divided into Group F1, Group F2, and Group F3 based on the fatty
      degeneration grade, the correlations of steatosis with inflammations, glucolipid
      metabolism, and liver functions were analyzed. At last, the regression analyses
      between steatosis and the inflammation grade, glucolipid metabolism and liver
      function indicators were conducted for Group F1, F2, and F3, respectively.
      RESULTS: In the chronic hepatitis B patients with steatosis, liver function
      indicators-alanine aminotransferase (ALT) and AST, levels of inflammatory factors
      interleukin-2 (IL-2), IL-6 and CRP and glucolipid metabolism indicators-fasting
      blood glucose (FBG), 2h postprandial blood glucose (2h PBG), fasting insulin
      (FINS), triacylglycerol (TG), total cholesterol (TC), and low-density lipoprotein
      (LDL) were significantly higher than those without steatosis (p<0.05). The
      steatosis, liver functions, and glucolipid metabolism indicators were
      statistically different between patients in the normal inflammatory factor group
      and the abnormal inflammatory factor group (p<0.06). In addition, the liver
      function indicators (ALT and AST) and glucolipid metabolism indicators (FBG, 2h
      PBG, FINS, TG, TC, HDL, and LDL) in the abnormal group were statistically higher
      than those of normal inflammatory factor group (p<0.05). In the normal liver
      function group, the average fatty degeneration grade was statistically lower than
      that in the abnormal liver function group (p<0.05), and glucolipid metabolism
      indicators (FBG, 2h PBG, FINS, TG, TC, IL-2, IL-6, CRP, HDL, and LDL) were also
      markedly lower than those in the abnormal liver function group (p<0.05). The
      steatosis was positively correlated with relevant indicators, including the blood
      glucose indicator of FBG (r=0.509, p<0.05), liver function indicator of AST
      (r=0.602, p<0.05), the blood lipid indicator of TG (r=0.740, p<0.05), and the
      inflammatory factor of CRP (r=0.882, p<0.05), respectively. The disease course,
      BMI, 2h FBG, FINS, TG, TC, HDL, LDL, AST, ALT, and inflammatory factors of IL-2,
      IL-6, and CRP were involved in risk factors of steatosis (p<0.05). CONCLUSIONS:
      Our data demonstrates that the steatosis is correlated with liver functions,
      glucolipid metabolism and inflammation level in chronic hepatitis B patients, and
      the foregoing indicators can affect the disease development of chronic hepatitis
      B patients with steatosis.

PMID- 30229841
TI  - Long non-coding RNA H19 protects acute myocardial infarction through activating
      autophagy in mice.
AB  - OBJECTIVE: We investigate the effect of long non-coding RNA H19 in acute
      myocardial infarction (AMI) and the underlying mechanism. MATERIALS AND METHODS:
      C57BL/6 mice were subjected to AMI and injected with lentivirus pcDNA-H19. After
      AMI procedures for 3 weeks, cardiac function was detected by echocardiography.
      The infarct size was stained by triphenyltetrazolium chloride. H19 expression in
      mice was measured by quantitative reverse transcriptase-polymerase chain reaction
      (qRT-PCR). Protein expressions of LC3, Beclin-1, and ATG-7 in mice were measured
      by Western blot. RESULTS: Our results indicated that H19 expression was
      significantly downregulated in the infarcted myocardium. Overexpression of H19
      after injection with pcDNA-H19 in mice could reduce infarct size and improve
      cardiac function through upregulating the ratio of LC3-II/I and expressions of
      Beclin-1 and ATG-7. CONCLUSIONS: Overexpression of H19 could protect AMI in mice
      via activating autophagy.

PMID- 30229842
TI  - Mechanism of vasoactive peptide intermedin in vascular collagen remodeling during
      angiotensin II-induced hypertention.
AB  - OBJECTIVE: Renin-angiotensin axis plays a pivotal role in the cardiovascular
      system, and Angiotensin II (Ang II) is of great importance in the progression of
      hypertension. Vasoactive peptide intermedin (IMD) belongs to calcitonin gene
      related peptide (CGRP) family, which is involved in the regulation of the
      cardiovascular function. This study aims to determine the effect of vasoactive
      peptide intermedin on vascular collagen remodeling caused by angiotensin II
      induced hypertension. MATERIALS AND METHODS: 12-week old rats were randomly
      assigned into three groups, and each group consisted of 12 rats. Rats were
      administered with Ang II or Ang II+IMD, respectively. Control group received
      saline administration. Blood pressure of caudal artery was examined two weeks
      after administration. Serum procollagen I and III were detected by enzyme-linked
      immunosorbent assay (ELISA). The vascular microstructure was examined via
      hematoxylin-eosin (HE) staining to evaluate vascular collagen remodeling.
      Expressions of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK)
      were tested by using Western-blot and RT-PCR. RESULTS: Compared with the control
      group (92.2+/-9.1 mmHg), blood pressure of group Ang II was increased by 88%
      (173.1+/-11.2 mmHg) (p<0.01). Moreover, blood pressure level in group Ang II+IMD
      (131.0+/-10.9 mmHg) was reduced compared to that in group Ang II (p<0.05).
      Compared with that in control group, higher level of serum procollagen, with
      significantly increasing vascular W/C ratio and collagen area percentage, was
      found in group Ang II, while all testing indexes above in group Ang II+IMD were
      lower than that in group Ang II. No differences were detected in the levels of
      Akt and MAPK mRNA among all three groups. However, highest expressions of
      phosphorylation Akt and MAPK protein were shown in group Ang II, and the levels
      were gradually lower in groups of Ang II+IMD and control. CONCLUSIONS: IMD could
      attenuate the vascular collagen remodeling caused by angiotensin II-induced
      hypertension via inhibiting phosphorylation of Akt and MAPK.

PMID- 30229843
TI  - The involvement of p38MAPK in the rat model of lower-extremity arterial ischemia
      reperfusion injury.
AB  - OBJECTIVE: This study aims to investigate the regulatory role of p38 mitogen
      activated protein kinase (p38MAPK) in rats with lower-extremity arterial ischemia
      reperfusion injury. MATERIALS AND METHODS: A total of 60 Sprague-Dawley (SD) rats
      were randomly divided into four groups: control group (Group A), lower-extremity
      arterial ischemia-reperfusion group (Group B), lower-extremity arterial ischemic
      postconditioning group (Group C), and lower-extremity arterial ischemic
      postconditioning + SB203580 group (Group D, 5 MUmol/L SB203580, the inhibitor of
      MAPK pathway, was injected after lower-extremity arterial ischemic
      postconditioning). The lower-extremity arterial vessels were collected after 24
      h. The apoptosis in the lower-extremity arterial vessel in each group was
      detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) method. The expression of phosphorylated (p)-p38MAPK was
      measured via Western blotting, and the level of p-activating transcription factor
      2 (ATF-2) was detected via immunohistochemical method. RESULTS: The positive rate
      of apoptotic cells (%) in Group B was significantly increased compared to that in
      Group A (p<0.05). However, the positive rate was statistically decreased by
      postcondition in Group C, the rate was further reduced after injection of
      SB203580 in Group D compared to Group B (p<0.05). Compared with that in Group C,
      the expressions of p-p38MAPK and p-ATF-2 in Group D were significantly
      downregulated after injection of SB203580 (p<0.05). CONCLUSIONS: Lower-extremity
      arterial ischemia-reperfusion postconditioning can significantly reduce the
      apoptosis level in vascular tissues, decrease the expressions of p-p38MAPK and
      downstream factor ATF-2, and alleviate the damage in lower-extremity arterial
      vessels. The inhibition of MAPK pathway further restricted the apoptosis and
      contributed to a promoting role in the recovery of lower-extremity arterial
      ischemia-reperfusion injury.

PMID- 30229844
TI  - Fasudil alleviates hepatic fibrosis in type 1 diabetic rats: involvement of the
      inflammation and RhoA/ROCK pathway.
AB  - OBJECTIVE: Rho-associated kinases (ROCKs) are recognized to be involved in many
      pathophysiological processes caused by hyperglycemia. We performed experiments to
      evaluate the effects of fasudil, the Rho/ROCK inhibitor, on preventing hepatic
      fibrosis in type 1 diabetic rats and to elucidate the underlying mechanisms.
      MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomly divided into five
      groups: normal control (NC), untreated diabetic (DM), low-dose fasudil-treated (L
      Fas), high-dose fasudil-treated (H-Fas) and captopril-treated (Cap) groups.
      Streptozotocin was injected to establish the diabetes model. Alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and inflammatory factors
      such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), were
      analyzed. Hematoxylin and eosin (HE) and Masson's trichrome staining were used
      for histological observations. The expression of transforming growth factor-beta
      (TGF-beta1), metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1
      (TIMP-1), collagen type Ialpha (Coll alpha1), nuclear factor-kappa B (NF-kappaB)
      and ROCK-1 were measured to investigate the mechanisms involved in fibrosis.
      RESULTS: The DM group exhibited hepatic fibrosis with remarkable liver damage and
      inflammation reaction by the activation of the NF-kappaB pathway. Treatment with
      fasudil or captopril suppressed not only the inflammation reaction but also the
      accumulation of the extracellular matrix due to the downregulation of TGF-beta1
      and MMP-9/TIMP-1, which induces the amelioration of the liver fibrosis with
      diabetes. Furthermore, fasudil significantly attenuated the activation of ROCK-1
      and NF-kappaB in the livers of diabetic rats. CONCLUSIONS: These results suggest
      that fasudil exert anti-inflammation actions and markedly decrease the
      accumulation of extracellular matrix. Fasudil is a good candidate agent for
      treating hepatic fibrosis in diabetes.

PMID- 30229845
TI  - DIXDC1 prevents oxygen-glucose deprivation/reoxygenation-induced injury in
      hippocampal neurons in vitro by promoting Wnt/beta-catenin signaling.
AB  - OBJECTIVE: Dishevelled-Axin (DIX) domain containing 1 (DIXDC1), a novel DIX
      domain-containing protein and a positive regulator of Wingless (Wnt) signaling,
      has previously been reported to play multiple roles in neurodevelopment and
      neurological disorders. However, whether DIXDC1 plays a role during cerebral
      ischemia/reperfusion injury remains unknown. In this study, we investigated the
      potential role of DIXDC1 in neuronal injury induced by oxygen-glucose deprivation
      and reoxygenation (OGD/R), an in vitro model of cerebral ischemia/reperfusion
      injury. MATERIALS AND METHODS: Neuronal injury was induced by OGD/R treatment.
      Relative mRNA expression of DIXDC1 was detected by real-time quantitative
      polymerase chain reaction (RT-qPCR). Protein expression of DIXDC1 and beta
      catenin was determined by Western blot. Cell viability was examined by the cell
      counting kit-8 assay. Cell cytotoxicity was detected by the lactate dehydrogenase
      assay. Cell apoptosis was detected by the caspase-3 activity assay. The activity
      of Wnt/beta-catenin signaling was detected by the luciferase reporter assay.
      RESULTS: TWe found that DIXDC1 expression was significantly upregulated in
      hippocampal neurons following OGD/R treatment. Small interfering RNA-mediated
      silencing of DIXDC1 significantly impaired viability and promoted cell injury and
      apoptosis in neurons with OGD/R treatment. In contrast, overexpression of DIXDC1
      increased the viability and reduced cell injury and apoptosis in neurons with
      OGD/R treatment, showing protective effects against OGD/R injury. Furthermore,
      our results showed that DIXDC1 promoted the expression of beta-catenin and
      activation of Wnt signaling. Notably, inhibition of Wnt signaling significantly
      abrogated DIXDC-mediated neuroprotective effects. CONCLUSIONS: Our results
      demonstrate that DIXDC1 prevents OGD/R-induced neuronal injury by promoting
      Wnt/beta-catenin signaling. Our study indicates that DIXDC1 may play an important
      role in cerebral ischemia and reperfusion serving as a potential target for the
      treatment of cerebral ischemia/reperfusion injury.

PMID- 30229846
TI  - Mifepristone alleviates cerebral ischemia-reperfusion injury in rats by
      stimulating PPAR gamma.
AB  - OBJECTIVE: To investigate the changes of peroxisome proliferator-activated
      receptor gamma (PPAR gamma) in focal cerebral ischemia-reperfusion injury, and to
      explore the effect and mechanism of mifepristone on the cerebral ischemia
      reperfusion injury. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were
      selected, and the middle cerebral artery occlusion and reperfusion (MCAO/R) rat
      model was constructed using the longa's suture-occluded method. The sham
      operation group was not inserted with occlusion sutures. All experimental rats
      were divided into four groups: the sham operation group (SHA group), the MCAO/R
      model group (MCR group), the mifepristone intervention group (MIF group) (3
      mg/kg, intragastric administration), and the mifepristone + bisphenol A
      diglycidyl ether (BADGE) intervention group (MIF+BAD group) [3 mg/kg mifepristone
      (intragastric administration) + 30 mg/kg BADGE (intraperitoneal injection)]. The
      long's scoring method (5 grades) was applied for scoring after reperfusion, at
      the time when the animals woke up, and at 48 h after awaking before execution,
      respectively. 48 h after the model was successfully established, triphenyl
      tetrazolium chloride (TTC) staining was performed to calculate the volume of
      cerebral infarction, and Nissl staining was conducted to observe the cranial
      nerve tissue morphology. Meanwhile, immune-histochemical staining was used to
      detect PPAR gamma. Moreover, the protein expression levels of PPAR gamma, tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), interleukin-6
      (IL-6), matrix metalloproteinase-2 (MMP-2), MMP-9 and tissue inhibitor of
      metalloproteinase 1 (TIMP-1) were examined by Western blotting (WB). RESULTS:
      Mifepristone could significantly enhance the neurological function after cerebral
      ischemia-reperfusion injury, reduce the volume of cerebral infarction, and
      improve the morphology of nerve tissues in rats. The expression of PPAR gamma in
      the brain tissues of rats after cerebral ischemia-reperfusion injury markedly
      declined, whereas mifepristone could remarkably increase the protein expression
      of PPAR gamma. After mifepristone intervention, the protein levels of TNF-alpha,
      IL-1beta, IL-6, MMP-2, and MMP-9 in the infarcted brain tissues of rats were
      markedly decreased, while the expression of the TIMP-1 protein was increased.
      When combined with BADGE, the effect of mifepristone was partially offset.
      CONCLUSIONS: Mifepristone acts as a PPAR gamma agonist, and relieves cerebral
      ischemia-reperfusion injury by restoring the balance between MMPs and TIMPs and
      inhibiting inflammatory cytokines.

PMID- 30229847
TI  - Effects of hydromorphone and morphine intravenous analgesia on plasma motilin and
      postoperative nausea and vomiting in patients undergoing total hysterectomy.
AB  - OBJECTIVE: To observe the effects of hydromorphone and morphine intravenous
      analgesia on plasma motilin and postoperative nausea and vomiting in patients
      undergoing a total hysterectomy. PATIENTS AND METHODS: 80 patients who underwent
      hysterectomy from April 2015 to June 2016 were randomly divided into two groups,
      with 40 patients in each group. The two groups received an intravenous infusion
      of hydromorphone or morphine for analgesia. The VAS pain score and Ramsey
      sedation score were recorded 4, 8, 12, 24, and 48 hours after the first dose of
      analgesia. The scores of nausea and vomiting were recorded. The levels of motilin
      were determined by radioimmunoassay before anesthesia, after anesthesia, during
      hysterectomy and 1 day after the operation. The results showed that the analgesic
      effect of hydromorphone was more rapid than morphine. RESULTS: There were
      significant differences in VAS scores between the two groups at each time point
      (p<0.05), indicating that the analgesic effect of hydromorphone was better than
      morphine's one. The scores of Ramsay sedation were less than 6 points at each
      time point within 48 hours after the operation. The content of plasma motilin in
      the hydromorphone group was higher than that in the morphine group during the
      first day after anesthesia. There were 34 cases (85%) of mild nausea and vomiting
      within 24 hours after the operation in the hydromorphone group. In the morphine
      group, there were 16 cases (40%) of mild nausea and vomiting within 24 hours
      after the operation, 10 cases (25%) of severe nausea and vomiting. CONCLUSIONS:
      The occurrence of severe malignant vomiting after the use of morphine was more
      than that after the use of hydromorphone. Normal level and function of motilin is
      the basis of avoiding nausea and vomiting. Too fast or too slow gastrointestinal
      motility can induce postoperative nausea and vomiting.

PMID- 30229848
TI  - Regulation by Pink1 on the mitochondrial dysfunction in endothelial cells post
      the hypoxia mimetic agent CoCl2 treatment.
AB  - OBJECTIVE: To explore the role of miR-451a in the migration and invasion of non
      small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: Quantitative Real
      time-polymerase chain reaction (qRT-PCR) and Western blot were performed to
      detect the levels of miR-451a and activating transcription factor 2 (ATF2) in
      NSCLC. Transwell assay was employed to analyze the migratory and invasive
      abilities in NSCLC cells. Dual-luciferase reporter assay was applied to confirm
      the binding condition of miR-451 and its target gene in NSCLC cells. RESULTS: MiR
      451a was downregulated in NSCLC tissues and lung cancer cell lines A549 and NCI
      H460, while ATF2 was upregulated. The mRNA level of miR-451a was negatively
      correlated to ATF2. Additionally, miR-451a regulated cell migration and invasion
      through targeting ATF2. Furthermore, ATF2 could reverse the inhibitory migration
      and invasion of A549 cells induced by miR-451a. CONCLUSIONS: MiR-451a inhibits
      the migratory and invasive abilities of NSCLC cells through ATF2 regulation. The
      newly identified miR-451a/ATF2 axis provides a novel insight into the
      pathogenesis of NSCLC.

PMID- 30229849
TI  - Protective effect of ulinastatin combined with dexmedetomidine on lung injury
      after cold ischemia-reperfusion in rats.
AB  - OBJECTIVE: We investigated the protective effect of ulinastatin combined with
      dexmedetomidine on lung injury after hepatic ischemia-reperfusion in rats.
      MATERIALS AND METHODS: A total of 60 healthy and clean male Sprague Dawley (SD)
      rats were divided into the blank control group (group O), the model control group
      (group K), the ulinastatin and dexmedetomidine group (group F) according to
      random number table with 20 rats in each group. RESULTS: The plasma
      concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      interleukin-8 (IL-8) and malondialdehyde (MDA) at T1, T2 and T3 time points in
      rats of the three groups were significantly higher than those of the T0 time
      point (p<0.05). The superoxide dismutase (SOD) activity in the plasma of rats of
      the three groups was significantly lower at T1, T2 and T3 time point when
      compared with that of T0 (p<0.05). The concentrations of TNF-alpha, IL-6, IL-8
      and MDA in group K at T1, T2 and T3 moments were significantly higher than those
      of group O (p<0.05). However, the concentrations of IL-6, IL-8, TNF-alpha and MDA
      in group F at T1, T2, T3 were significantly lower than those of group K (p<0.05).
      The activities of SOD in group K at T1, T2, T3 were all significantly higher than
      those of group O (p<0.05). Meanwhile, the activities of SOD in group F at T1, T2,
      T3 were significantly higher than those of group K (p<0.05). CONCLUSIONS:
      Ulinastatin combined with dexmedetomidine can reduce the inflammatory response
      and inhibit lipid peroxidation, eventually alleviating acute lung injury after
      hepatic ischemia-reperfusion in rats.

PMID- 30229851
TI  - Effectiveness of antimicrobial-coated sutures for the prevention of surgical site
      infection: a review of the literature.
AB  - OBJECTIVE: Surgical site infections (SSIs) are the third most common hospital
      acquired infections and account for 14% to 16% of all such infections, and suture
      material may play a role in SSI rate. Given this risk of infection, sutures with
      antimicrobial activity have been developed. Both in vitro and in vivo experiments
      have shown that triclosan-coated sutures (TCS) are effective in the prevention of
      SSIs. Our aim is to analyze currently available RCTs, comparing the effect of
      antimicrobial-coated suture (ACS) with uncoated suture on the occurrence of SSIs
      following surgical procedures, we highlighted major contributions of most
      significant studies and evaluate the current "state of the art" on antimicrobial
      coated sutures. MATERIALS AND METHODS: We reviewed 15 RCTs comparing
      antimicrobial-coated sutures with conventional sutures and assessing the clinical
      effectiveness of antimicrobial sutures to decrease the risk for SSIs. We focused
      our attention on each variable in all the analyzed study. RESULTS: Our selected
      RCTs, produced controversial results: 7 RCTs demonstrated a significant benefit,
      on the contrary, 8 RCTs presented a comparison in which there was no difference.
      CONCLUSIONS: On the basis of our selected trial results and the heterogeneous
      findings of our 7 selected meta-analyses, we conclude that even though the
      question of whether TCSs could reduce the occurrence of SSI remains still open,
      the antimicrobial suture was effective in decreasing the risk for postoperative
      SSIs in a broad population of patients undergoing surgery. Alternative substances
      are becoming clinically relevant, such as Chlorhexidine (CHX) coated sutures and
      only 6 in vivo scientific studies evaluated them. In vivo studies, large and
      comparative clinical research trials are necessary to validate the efficacy of
      CHX-coated sutures thus allowing their use in clinical practice.

PMID- 30229850
TI  - Effects of Ulinastatin on myocardial oxidative stress and inflammation in
      severely burned rats.
AB  - OBJECTIVE: By constructing the severe burns model in rat, we explored the effects
      of different doses of Ulinastatin (UTI) on protecting myocardium from oxidative
      stress and inflammatory reaction. MATERIALS AND METHODS: The severe burns model
      in rat was first constructed. Burned rats were intervened with different doses of
      UTI. Contents of cardiac troponin I (cTnI), Interleukin-1 (IL-1), Interleukin-6
      (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in rat serum and heart
      homogenate were detected by enzyme-linked immunosorbent assay (ELISA). Activities
      of SOD (superoxide dismutase), CAT (catalase), GSH-Px (glutathione peroxidase),
      and MDA (malondialdehyde) were detected by commercial kits. The inflammation and
      pathological changes in rat heart were observed by HE (Hematoxylin-Eosin)
      staining. Protein expressions of Cox-2, iNOS, NF-kappaB, Nrf2, and HO-1 in rat
      myocardium were detected by Western blot. RESULTS: Higher levels of cTnI, IL-1,
      IL-6, and TNF-alpha were found in model group than those of control group
      (p<0.05). Besides, decreased contents of cTnI, IL-1, IL-6, and TNF-alpha were
      observed in both UTI 50 ku/kg group and UTI 100 ku/kg group compared with those
      of model group (p<0.05). Decreased activities of SOD, CAT, and GSH-Px, as well as
      increased MDA level were observed in model group than those of control group
      (p<0.05). However, UTI treatment remarkably elevated SOD, CAT, and GSH-Px
      activities, whereas downregulated MDA level in burned rats (p<0.05). Abundant
      infiltration of inflammatory cells was found in the rat's myocardium of model
      group, which was alleviated in UTI group in a dose-dependent manner. Upregulated
      Cox-2, iNOS, and NF-kappaB, as well as downregulated Nrf2 and HO-1 were found in
      model group compared with those of control group (p<0.05). UTI pretreatment
      remarkably reversed the above-mentioned trends. CONCLUSIONS: Ulinastatin
      alleviates myocardial injury induced by severe burns. It exerts a protective role
      in myocardium via inhibiting oxidative stress and inflammatory response.

PMID- 30229852
TI  - Clinical treatment efficiency of mechanical thrombectomy combined with rhPro-UK
      thrombolysis for acute moderate/severe cerebral infarction.
AB  - OBJECTIVE: This study aims to compare clinical efficiency of mechanical
      thrombectomy combined with rhPro-UK thrombolysis on moderate or severe acute
      brain infarction. PATIENTS AND METHODS: A total of 90 acute cerebral infarction
      patients due to artery stenosis or blockade from May 2016 to May 2017 were
      recruited and randomly assigned into thrombolysis group (N = 30), mechanical
      thrombectomy (N = 30), and combined treatment group (N = 30). Clinical
      information was collected. Thrombolysis group received rhPro-UK, mechanical
      thrombectomy group received Solitaire scaffold, and combined group received rhPro
      UK after Solitaire scaffold. Barthel scale and NIHSS scale were used to evaluate
      the quality of life and mental deficit of patients. Modified thrombolysis in
      cerebral infarction (mTICI) was compared among three groups, along with the
      observation of hemorrhage, neurological recovery within 90 days, and adverse
      effects. RESULTS: No significant difference was found in NIHSS within 24 h of
      treatment among three groups (p > 0.05), but the decreasing levels were shown at
      24 h, 7 days, and 90 days comparing to those before treatment (p < 0.05). In
      combined treatment group, lower NIHSS at 7 d and 90 d were detected comparing to
      other two groups (p < 0.05). Recanalization rates were 53.33% and 60.00% in
      thrombolysis and mechanical groups (p > 0.05), respectively, which were
      significantly lower than that in combined group (83.33%) (p < 0.05). Curative
      rate in combined group was 70%, significantly higher than thrombolysis (46.67%)
      and mechanical group (53.33%) (p < 0.05). No statistical difference of curative
      rate was observed between thrombolysis and mechanical groups (p > 0.05).
      Moreover, neither significant difference of coagulation function nor platelet
      count was found among three groups (p > 0.05). CONCLUSIONS: Mechanical
      thrombectomy combined with thrombolysis presented favorable efficiency in the
      treatment of moderate to severe acute cerebral infarction than single treatment,
      among which the occurrence of adverse effects were similar.

PMID- 30229853
TI  - Childhood multiple sclerosis: clinical features and recent developments on
      treatment choices and outcomes.
AB  - Multiple sclerosis (MS) is an inflammatory idiopathic autoimmune disease causing
      demyelination of central nervous system (CNS). The incidence of pediatric MS is
      relatively rare, affecting 0.2 to 0.64/100,000 subjects; cases with MS onset
      before age 10-12 years, account for less than 1% of all MS cases, while 2.7 to
      10.5% of all MS cases worldwide are seen in children <18 years of age, with a
      strong female preponderance. The disease course of MS varies from a benign type
      with relatively low level of disability after a long duration (15 years) of the
      disease, to a malignant type of MS with severe disability or even death within
      few months following onset. Diagnostic criteria for pediatric MS include >= 2
      clinical events involving more areas of CNS inflammation in the absence of
      encephalopathy, separated by > 30 days, along with the involvement of brainstem.
      Pediatric MS generally presents relapsing-remittent form of MS, with majority of
      the patients recovering from the first attack. Major histocompatibility complex,
      more specifically, mutations in the human leukocyte antigen (HLA) DRB1*15 allele,
      are considered most important genetic factors that are contributory to the
      disease. Treatment choices for pediatric MS include many disease-modifying
      therapies (DMT) that are currently being used for adult MS and these are
      interferon-beta 1a/1b (IFN-beta1a/1b), glatiramer acetate, teriflunomide,
      dimethyl fumarate, alemtuzumab, etc. However, most of these have not gone through
      complete testing in randomized, placebo-controlled clinical trials for pediatric
      MS and are being prescribed off-label by clinicians. As these studies are
      progressing, it is important to address if these approaches of treating pediatric
      MS patients have any long-term impact on patients, in particular, physical,
      cognitive, developmental and social outcomes of the children.

PMID- 30229854
TI  - Molecular basis of trigeminal nerve disorders and healing.
AB  - OBJECTIVE: This review aims to describe trigeminal neuralgia and the molecular
      basis contributing to the pathophysiology of this condition by focusing on the
      state of the art. PATIENTS AND METHODS: An electronic search of PubMed was
      performed using the following keywords: "trigeminal neuralgia" AND
      "classification", "pathophysiology," "molecular basis" and "mitochondrial role."
      RESULTS: Mitochondrial abnormality, whether functional or morphological, can
      contribute to neurological disorders. Additionally, one recent finding showed
      that gain-of-function mutation in the voltage-gated sodium channel NaV1.6
      contributes to the pathophysiology of trigeminal neuralgia by increasing the
      excitability of trigeminal nerve ganglion neurons. It also exacerbates the
      pathophysiology of vascular compression. Healing of the trigeminal nerve is
      controlled by many molecular signaling pathways, including extracellular-signal
      regulated kinase, c-Jun, p38, Notch, and mitogen-activated protein kinases.
      CONCLUSIONS: More investigations regarding the gain-of-function mutation of
      NaV1.6 sodium channels are essential for the diagnosis and treatment of
      trigeminal nerve disorders, regardless of whether these are associated with
      vascular compression or not.

PMID- 30229855
TI  - Hypothalamus enlargement in mood disorders.
AB  - OBJECTIVE: The purpose of this study was to determine, in vivo, whether the
      hypothalamus volume is reduced in patients with mood disorders. METHODS: The
      cross-sectional study included 20 unmedicated (MDDu) and 20 medicated patients
      with major depressive disorder, 21 patients with bipolar disorder, and 23
      controls. Twenty of the controls were matched to the MDDu. Seven Tesla, T1
      weighted magnetic resonance images were acquired and processed using methods
      specifically developed for high-precision volumetry of the hypothalamus. RESULTS:
      An overall group difference was observed for the left hypothalamus volume
      corrected for intracranial volume. Planned contrasts identified that the left
      hypothalamus was approximately 5% larger in each patient group compared with the
      control group. A paired t-test with the 20 matched pairs of MDDu and controls and
      without correction for covariates confirmed the larger left hypothalamus volume
      in MDDu. CONCLUSIONS: Contrary to our expectations, the hypothalamus volume was
      increased in patients with uni- and bipolar affective disorders. The effect was
      left-sided and independent of medication status or statistical correction for
      covariates. Supported by emerging evidence that the stress response may be
      related to structural and functional asymmetry in the brain, our finding suggests
      a crucial role of the hypothalamus in mood disorders.

PMID- 30229856
TI  - High risk of early neurological worsening of lacunar infarction.
AB  - BACKGROUND AND PURPOSE: We aimed to evaluate factors associated with neurological
      worsening among patients with lacunar or non-lacunar infarction admitted within 3
      hours and between 3 and 24 hours after stroke onset. METHODS: All patients
      admitted to Haukeland university hospital between 2006 and 2016 with acute
      cerebral infarction on MRI and admission within 24 hours were included. Repeated
      National Institute of Health Stroke Scale (NIHSS) scoring was performed in all
      patients whenever possible. Neurological worsening during the hospital stay was
      defined as NIHSS score increase >=3 compared to NIHSS score on admission.
      RESULTS: In patients with lacunar infarction admitted within 3 hours of onset,
      neurological worsening was associated with low NIHSS score on admission, low body
      temperature, and leukoaraiosis, whereas only internal carotid artery stenosis or
      occlusion was associated with neurological worsening in non-lacunar infraction.
      For patients admitted 3-24 hours after onset, neurological worsening was
      associated with low body temperature, high systolic blood pressure, and short
      time from onset to admission in patients with lacunar infarction, whereas high
      systolic blood pressure, high NIHSS score on admission, middle cerebral artery
      occlusion, and high blood glucose were associated with neurological worsening in
      patients with non-lacunar infarction (all P < 0.05). CONCLUSIONS: Lacunar
      infarctions with minor neurological deficits within 3 hours of stroke onset are
      at high risk of neurological worsening especially if concomitant low body
      temperature and leukoaraiosis.

PMID- 30229857
TI  - Oropharyngeal leak pressure of the LMA ProtectorTM vs the LMA SupremeTM; a
      prospective, randomized, controlled clinical trial.
AB  - BACKGROUND: Clinical characteristics such as oropharyngeal leak pressure (OLP)
      and ventilation peak pressure are important factors for successful use of
      supraglottic airway devices in general anaesthesia. We hypothesized that the LMA
      ProtectorTM compared to the LMA SupremeTM may develop a higher OLP, which could
      be of clinical significance. METHODS: Ninety-six patients were randomized to the
      LMA ProtectorTM or LMA SupremeTM groups. We measured oropharyngeal leak pressure
      within 5 minutes after insertion of the supraglottic airway device with a
      standardized cuff pressure at 60 cm H2 O. Secondary parameters, such as insertion
      time of the supraglottic airway device, the number of attempts inserting the
      supraglottic airway device and the gastric tube, volume of gastric contents, and
      maximum airway pressure, as well as pulse oximetry throughout the operation were
      measured. Further, blood staining after removal of the supraglottic airway device
      and postoperative airway morbidity 3 hours after surgery were determined.
      RESULTS: The mean difference of oropharyngeal leak pressure was 5.2 (95% CI 2.8
      7.6), ie, 30.9 (7.4) cmH2 O for the LMA ProtectorTM vs 25.6 (4.4) cmH2 O for the
      LMA SupremeTM (P < 0.001; mean(SD)). Similarly, there was a mean difference
      between OLP and maximal ventilation peak pressure 5.6 (95% CI 3.1-8.2) ie 19.6
      (7.7) cmH2 O for the LMA ProtectorTM vs 14.0 (4.4) cmH2 O for the LMA SupremeTM
      (P < 0.001). No difference was found between the groups for other secondary
      parameters, as well as postoperative airway morbidity. CONCLUSION: The LMA
      ProtectorTM enabled a higher OLP compared to the LMA SupremeTM. This finding may
      be important for patients requiring a higher peak pressure for sufficient
      supraglottic airway device ventilation.

PMID- 30229858
TI  - Social egg freezing: Early is not always best.

PMID- 30229859
TI  - Pseudoxanthoma elasticum: Dermoscopy and mutation analysis.

PMID- 30229860
TI  - High-throughput identification of factors promoting neuronal differentiation of
      human neural progenitor cells in microscale 3D cell culture.
AB  - Identification of conditions for guided and specific differentiation of human
      stem cell and progenitor cells is important for continued development and
      engineering of in vitro cell culture systems for use in regenerative medicine,
      drug discovery, and human toxicology. Three-dimensional (3D) and organotypic cell
      culture models have been used increasingly for in vitro cell culture because they
      may better model endogenous tissue environments. However, detailed studies of
      stem cell differentiation within 3D cultures remain limited, particularly with
      respect to high-throughput screening. Herein, we demonstrate the use of a
      microarray chip-based platform to screen, in high-throughput, individual and
      paired effects of 12 soluble factors on the neuronal differentiation of a human
      neural progenitor cell line (ReNcell VM) encapsulated in microscale 3D Matrigel
      cultures. Dose-response analysis of selected combinations from the initial
      combinatorial screen revealed that the combined treatment of all-trans retinoic
      acid (RA) with the glycogen synthase kinase 3 inhibitor CHIR-99021 (CHIR)
      enhances neurogenesis while simultaneously decreases astrocyte differentiation,
      whereas the combined treatment of brain-derived neurotrophic factor and the small
      azide neuropathiazol enhances the differentiation into neurons and astrocytes.
      Subtype specification analysis of RA- and CHIR-differentiated cultures revealed
      that enhanced neurogenesis was not biased toward a specific neuronal subtype.
      Together, these results demonstrate a high-throughput screening platform for
      rapid evaluation of differentiation conditions in a 3D environment, which will
      aid the development and application of 3D stem cell culture models.

PMID- 30229862
TI  - Clinical Factors and Rate of Cough During Angiotensin-Converting Enzyme Inhibitor
      Treatment.

PMID- 30229861
TI  - Lewy body pathology in Alzheimer's disease: A clinicopathological prospective
      study.
AB  - OBJECTIVE: Identify clinical features predictive of Lewy body pathology in
      Alzheimer's disease (AD) patients in an ongoing longitudinal clinicopathologic
      study. MATERIAL AND METHODS: We queried the Arizona Study of Aging and
      Neurodegenerative Disorders (AZSAND) database for dementia cases with AD
      pathology (1997-2015). Subjects received longitudinal comprehensive clinical
      evaluations including motor/neuropsychological assessment and Apo-E4 genotyping.
      All cases were autopsied and had standard neuropathological assessments for AD
      and Lewy-type synucleinopathy (LTS). Subjects were categorized based on
      standardized pathological criteria with AD cases that had LTS but did not meet
      DLB pathologic criteria being categorized as ADLB. We performed pairwise
      comparison between the different diagnoses and multivariable modelling to
      identify clinical symptoms that predict the pathological diagnosis. RESULTS: We
      identified 32 DLB/AD, 54 ADLB, 70 AD only and 41 PDD/AD cases. AD subjects with
      LTS pathology had higher UPDRS II and III total scores as well as generally
      higher individual scores compared to AD alone. While depression scales and Trail
      making Test A correlated significantly with LTS, other neuropsychological
      variables were not significantly different. Apo E4 occurrence was similar in all
      groups (40%-49%). CONCLUSIONS: Our study suggests that the presence (or absence)
      of LTS influences motor and non-motor clinical findings in AD patients. These
      findings may lead to biomarkers that allow for more targeted treatment of AD.

PMID- 30229863
TI  - Exosomes in HNSCC plasma as surrogate markers of tumour progression and immune
      competence.
AB  - Exosomes in plasma of head and neck squamous cell carcinoma (HNSCC) patients
      comprise subsets of vesicles derived from various cells. Recently, we separated
      CD3(+) from CD3(-) exosomes by immune capture. CD3(-) exosomes were largely
      tumour-derived (CD44v3+ ). Both subsets carried immunosuppressive proteins and
      inhibited functions of human immune cells. The role of these subsets in immune
      cell reprogramming by the tumour was investigated by focusing on the adenosine
      pathway components. Spontaneous adenosine production by CD3(+) or CD3(-) exosomes
      was measured by mass spectrometry, as was the production of adenosine by CD4+
      CD39+ regulatory T cells (Treg ) co-incubated with these exosomes. The highest
      level of CD39/CD73 ectoenzymes and of adenosine production was found in CD3(-)
      exosomes in patients with the stages III/IV HNSCCs). Also, the production of 5'
      AMP and purines was significantly higher in Treg co-incubated with CD3(-) than
      CD3(+) exosomes. Consistently, CD26 and adenosine deaminase (ADA) levels were
      higher in CD3(+) than CD3(-) exosomes. ADA and CD26 levels in CD3(+) exosomes
      were significantly higher in patients with early (stages I/II) than advanced
      (stages III/IV) disease. HNSCC patients receiving and responding to photodynamic
      therapy had increased ADA levels in CD3(+) exosomes with no increase in CD3(-)
      exosomes. The opposite roles of CD3(+) ADA+ CD26+ and CD3(-) CD44v3+ adenosine
      producing exosomes in early versus advanced HNSCC suggest that, like their parent
      cells, these exosomes serve as surrogates of immune suppression in cancer.

PMID- 30229864
TI  - Combinatorial lentiviral gene delivery of pro-oligodendrogenic factors for
      improving myelination of regenerating axons after spinal cord injury.
AB  - Spinal cord injury (SCI) results in paralysis below the injury and strategies are
      being developed that support axonal regrowth, yet recovery lags, in part, because
      many axons are not remyelinated. Herein, we investigated strategies to increase
      myelination of regenerating axons by overexpression of platelet-derived growth
      factor (PDGF)-AA and noggin either alone or in combination in a mouse SCI model.
      Noggin and PDGF-AA have been identified as factors that enhance recruitment and
      differentiation of endogenous progenitors to promote myelination. Lentivirus
      encoding for these factors was delivered from a multichannel bridge, which we
      have previously shown creates a permissive environment and supports robust axonal
      growth through channels. The combination of noggin+PDGF enhanced total
      myelination of regenerating axons relative to either factor alone, and
      importantly, enhanced functional recovery relative to the control condition. The
      increase in myelination was consistent with an increase in oligodendrocyte
      derived myelin, which was also associated with a greater density of cells of an
      oligodendroglial lineage relative to each factor individually and control
      conditions. These results suggest enhanced myelination of regenerating axons by
      noggin+PDGF that act on oligodendrocyte-lineage cells post-SCI, which ultimately
      led to improved functional outcomes.

PMID- 30229865
TI  - Synthetic repetitive extragenic palindromic (REP) sequence as an efficient mRNA
      stabilizer for protein production and metabolic engineering in prokaryotic cells.
AB  - In prokaryotic cells, 3'-5' exonucleases can attenuate messenger RNA (mRNA)
      directionally from the direction of the 3'-5' untranslated region (UTR), and thus
      improving the stability of mRNAs without influencing normal cell growth and
      metabolism is a key challenge for protein production and metabolic engineering.
      Herein, we significantly improved mRNA stability by using synthetic repetitive
      extragenic palindromic (REP) sequences as an effective mRNA stabilizer in two
      typical prokaryotic microbes, namely, Escherichia coli for the production of
      cyclodextrin glucosyltransferase (CGTase) and Corynebacterium glutamicum for the
      production of N-acetylglucosamine (GlcNAc). First, we performed a high-throughput
      screen to select 4 out of 380 REP sequences generated by randomizing 6
      nonconservative bases in the REP sequence designed as the degenerate base "N."
      Secondly, the REP sequence was inserted at several different positions after the
      stop codon of the CGTase-encoding gene. We found that mRNA stability was improved
      only when the space between the REP sequence and stop codon was longer than 12
      base pairs (bp). Then, by reconstructing the spacer sequence and secondary
      structure of the REP sequence, a REP sequence with 8 bp in a stem-loop was
      obtained, and the CGTase activity increased from 210.6 to 291.5 U/ml.
      Furthermore, when this REP sequence was added to the 3'-UTR of glucosamine-6
      phosphate N-acetyltransferase 1 ( GNA1), which is a gene encoding a key enzyme
      GNA1 in the GlcNAc synthesis pathway, the GNA1 activity was increased from 524.8
      to 890.7 U/mg, and the GlcNAc titer was increased from 4.1 to 6.0 g/L in C.
      glutamicum. These findings suggest that the REP sequence plays an important
      function as an mRNA stabilizer in prokaryotic cells to stabilize its 3'-terminus
      of the mRNA by blocking the processing action of the 3'-5' exonuclease. Overall,
      this study provides new insight for the high-efficiency overexpression of target
      genes and pathway fine-tuning in bacteria.

PMID- 30229866
TI  - Drug-delivering nerve conduit improves regeneration in a critical-sized gap.
AB  - Autologous nerve grafts are the current "gold standard" for repairing large nerve
      gaps. However, they cause morbidity at the donor nerve site and only a limited
      amount of nerve can be harvested. Nerve conduits are a promising alternative to
      autografts and can act as guidance cues for the regenerating axons, without the
      need to harvest donor nerve. Separately, it has been shown that localized
      delivery of GDNF can enhance axon growth and motor recovery. FK506, an FDA
      approved small molecule, has also been shown to enhance peripheral nerve
      regeneration. This paper describes the design of a novel hole-based drug delivery
      apparatus integrated with a polytetrafluoroethylene (PTFE) nerve conduit for
      controlled local delivery of a protein such as GDNF or a small molecule such as
      FK506. The PTFE devices were tested in a diffusion chamber, and the bioactivity
      of the released media was evaluated by measuring neurite growth of dorsal root
      ganglions (DRGs) exposed to the released drugs. The drug delivering nerve guide
      was able to release bioactive concentrations of FK506 or GDNF. Following these
      tests, optimized drug releasing nerve conduits were implanted across 10 mm
      sciatic nerve gaps in a BL6 yellow fluorescent protein (YFP) mouse model, where
      they demonstrated significant improvement in muscle mass, compound muscle action
      potential, and axon myelination in vivo as compared with nerve conduits without
      the drug. The drug delivery nerve guide could release drug for extended periods
      of time and enhance axon growth in vitro and in vivo.

PMID- 30229867
TI  - On assessing binary regression models based on ungrouped data.
AB  - Assessing a binary regression model based on ungrouped data is a commonly
      encountered but very challenging problem. Although tests, such as Hosmer-Lemeshow
      test and le Cessie-van Houwelingen test, have been devised and widely used in
      applications, they often have low power in detecting lack of fit and not much
      theoretical justification has been made on when they can work well. In this
      article, we propose a new approach based on a cross-validation voting system to
      address the problem. In addition to a theoretical guarantee that the
      probabilities of type I and II errors both converge to zero as the sample size
      increases for the new method under proper conditions, our simulation results
      demonstrate that it performs very well.

PMID- 30229868
TI  - Exercise and nutrition may prolong the lives of patients with colon cancer.

PMID- 30229869
TI  - Blocking of YY1 reduce neutrophil infiltration by inhibiting IL-8 production via
      the PI3K-Akt-mTOR signaling pathway in rheumatoid arthritis.
AB  - Our previous study revealed that Yin Yang 1(YY1) played an important part in
      promoting interleukin (IL)-6 production in rheumatoid arthritis (RA). However,
      whether YY1 has any role in regulation of IL-8 in RA remains unclear. YY1 and IL
      8 expression in RA patients were analyzed by real-time polymerase chain reaction
      (PCR). Ingenuity pathway analysis (IPA) was used to analyze the signaling pathway
      involved in YY1-induced IL-8 production. The expression of YY1 and proteins
      involved in the pathway were detected by Western blot and enzyme-linked
      immunosorbent assay (ELISA). Migration of neutrophils was performed by chemotaxis
      assay. In this study, we found that high expression of IL-8 was positively
      associated with YY1 expression in RA. Blocking YY1 expression by YY1-short
      hairpin (sh)RNA lentivirus reduced IL-8 production. Mechanistically, we showed
      YY1 activated IL-8 production via the phosphatidylinositol-3-kinase/Akt/mammalian
      target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Further, using a co
      culture system consisting of peripheral blood mononuclear cells (PBMC) and
      neutrophils, we found that migration of neutrophils would be inhibited by YY1 RNA
      interference. Finally, using the collagen-induced arthritis animal model, we
      showed that treatment with the YY1-shRNA lentivirus led to reduction of IL-8
      levels and attenuation of inflammation and neutrophil infiltration in vivo. Our
      results reveal a role of YY1 involved in neutrophil infiltration in RA via the
      PI3K/Akt/mTOR/IL-8 signaling pathway. YY1 may be a new therapeutic target for
      treatment of RA.

PMID- 30229871
TI  - Frequent use of tests to monitor metastatic prostate cancer often may be
      unwarranted.

PMID- 30229870
TI  - Accuracy of surgical complication rate estimation using ICD-10 codes.
AB  - BACKGROUND: The ICD-10 codes are used globally for comparison of diagnoses and
      complications, and are an important tool for the development of patient safety,
      healthcare policies and the health economy. The aim of this study was to
      investigate the accuracy of verified complication rates in surgical admissions
      identified by ICD-10 codes and to validate these estimates against complications
      identified using the established Global Trigger Tool (GTT) methodology. METHODS:
      This was a prospective observational study of a sample of surgical admissions in
      two Norwegian hospitals. Complications were identified and classified by two
      expert GTT teams who reviewed patients' medical records. Three trained reviewers
      verified ICD-10 codes indicating a complication present on admission or emerging
      in hospital. RESULTS: A total of 700 admissions were drawn randomly from 12 966
      procedures. Some 519 possible complications were identified in 332 of 700
      admissions (47.4 per cent) from ICD-10 codes. Verification of the ICD-10 codes
      against information from patients' medical records confirmed 298 as in-hospital
      complications in 141 of 700 admissions (20.1 per cent). Using GTT methodology,
      331 complications were found in 212 of 700 admissions (30.3 per cent). Agreement
      between the two methods reached 83.3 per cent after verification of ICD-10 codes.
      The odds ratio for identifying complications using the GTT increased from 5.85
      (95 per cent c.i. 4.06 to 8.44) to 25.38 (15.41 to 41.79) when ICD-10
      complication codes were verified against patients' medical records. CONCLUSION:
      Verified ICD-10 codes strengthen the accuracy of complication rates. Use of non
      verified complication codes from administrative systems significantly
      overestimates in-hospital surgical complication rates.

PMID- 30229872
TI  - Risk of first-time and recurrent depression in patients with psoriasis: a
      population-based cohort study.
AB  - BACKGROUND: Psoriasis impairs quality of life, but it is unknown whether
      psoriasis is also an independent risk factor for depression. OBJECTIVES: To
      evaluate the incidence and risk of new and recurrent depression in patients with
      psoriasis. METHODS: We used individual-level linkage of Danish administrative
      registers. Patients with psoriasis aged >= 18 years between 1 January 1997 and 31
      December 2016 were matched 1 : 1 with individuals without psoriasis. Incidence
      rates were calculated and adjusted hazard ratios (HRs) estimated by Cox
      regression. RESULTS: There were 247 755 patients with psoriasis: 220 721 were
      treated with topicals (mild psoriasis), 24 771 with systemic nonbiologics
      (moderate psoriasis) and 2263 with biological therapy (severe psoriasis). The
      same number of matched referents without psoriasis were also analysed. During a
      maximum 20 years of follow-up, 45 641 patients with psoriasis and 36 299
      referents developed depression. In adjusted models, the HRs (95% confidence
      interval) of depression were 1.19 (1.17-1.20), 1.19 (1.15-1.23) and 1.50 (1.23
      1.84) for mild, moderate and severe psoriasis, respectively. The highest risk was
      observed among patients with severe psoriasis aged 40-50 years. Concurrent
      inflammatory bowel disease, but not psoriatic arthritis, was associated with
      increased risk of depression. The incidence of depression was markedly higher
      among patients with previous depression. CONCLUSIONS: Psoriasis was independently
      associated with risk of depression. These results may help clinicians identify
      particularly high-risk individuals.

PMID- 30229873
TI  - Multiple "halo nevi" occurring during pembrolizumab treatment for metastatic
      melanoma.

PMID- 30229874
TI  - Mutation in the SR6 region of desmoplakin is associated with pustular
      psoriasiform rash and left ventricular dysfunction.

PMID- 30229875
TI  - Plasma cell vulvitis: further confirmation of the diagnostic utility of
      dermoscopy.

PMID- 30229876
TI  - Cutaneous effects associated with fluconazole in patients treated for
      coccidioidomycosis.
AB  - BACKGROUND: Fluconazole is the most commonly used antifungal treatment for
      various forms of coccidioidomycosis. Although we had anecdotally observed a high
      proportion of patients reporting cutaneous adverse effects associated with
      fluconazole treatment, this observation was not well described in the medical
      literature, and we were unsure of the additional effect of the arid desert
      environment of Arizona. METHODS: We performed a one-time, voluntary survey of
      patients with coccidioidomycosis and compared the responses of patients treated
      with fluconazole with those of untreated patients. RESULTS: From January 1, 2015,
      to August 22, 2017, 62 fluconazole-treated and 35 untreated patients with
      coccidioidomycosis provided consent and were enrolled in the study; demographics
      were similar between the two groups. Among the 62 fluconazole-treated patients,
      daily dosages ranged from 200 mg to 800 mg. However, most (44/62, 71%) took 400
      mg daily, the typical dose for the treatment of coccidioidomycosis. The median
      fluconazole treatment duration at the time of study participation was 6 months.
      When compared with untreated patients, those taking fluconazole had more moderate
      to severe dry lips (74.2% [46/62] vs. 23.5% [8/34]; P < 0.001), dry skin (45.8%
      [27/59] vs. 22.9% [8/35]; P = 0.03), and alopecia (31.1% [19/61] vs. 11.4%
      [4/35]; P = 0.004). CONCLUSIONS: For the treatment of coccidioidomycosis,
      patients receiving fluconazole reported significantly more severe cutaneous
      effects, including dry lips, dry skin, and alopecia, than untreated patients. Our
      findings identify an association but do not prove causality.

PMID- 30229877
TI  - Aversion caused by skin diseases - a crowdsourcing study.
AB  - BACKGROUND: Disgust is a universal emotion that plays a role in reducing people's
      exposure to situations with risks of contamination. By the same token, skin
      diseases could generate aversion in observers. The present study aimed to assess
      the aversion triggered when viewing skin disease lesions on the face and hands.
      METHODS: A questionnaire was applied over the Internet containing demographic
      questions, assessment of personal sensitivity to disgust - by the Disgust Scale
      Revised (DS-R) -, and the aversion triggered when viewing eight images of skin
      diseases using an image aversion score (IAS) ranging from 0 to 10. RESULTS: Six
      hundred forty-nine people responded, 49% female, with a median age of 26 (p25
      p75: 22-34). A total of 2596 evaluations of images were collected. The overall
      IAS median was 2 (0-4), and Cronbach's alpha resulted 0.87. There was a
      significant correlation between DS-R and IAS (Spearman's rho = 0.42; P < 0.01).
      Seven-hundred twenty-four (28%) evaluations were considered as contagious
      diseases and received higher IAS: 5 (2-7) * 1 (0-3); P < 0.01. In multivariate
      analysis, the higher IAS was independently associated with male gender, with no
      children, not working as a health professional or caregiver, and presenting
      higher DS-R (P < 0.01). By analyzing the IAS according to morphological
      characteristics, we identified lower scores for macular dyschromic lesions (P <
      0.01). CONCLUSIONS: The aversion triggered by skin lesions varies according to
      the personal characteristics of the observer and the morphology of the lesion,
      being lower for macular dyschromic lesions, and associated with disgust
      sensitivity and the assignment of contagiousness to the lesion.

PMID- 30229878
TI  - Reflectance confocal microscopy of tinea capitis: comparing images with results
      of dermoscopy and mycological exams.

PMID- 30229879
TI  - Asymptomatic indurated plaque on the tongue in an immunocompetent man.

PMID- 30229880
TI  - C5a anaphylatoxin and its role in critical illness-induced organ dysfunction.
AB  - Critical illness is an aetiologically and clinically heterogeneous syndrome that
      is characterised by organ failure and immune dysfunction. Mortality in critically
      ill patients is driven by inflammation-associated organ damage and a profound
      vulnerability to nosocomial infection. Both factors are influenced by the
      activated complement protein C5a, released by unbridled activation of the
      complement system during critical illness. C5a exerts deleterious effects on
      organ systems directly and suppresses antimicrobial functions of key immune
      cells. Whilst several recent reports have added key knowledge of the cellular
      signalling pathways triggered by C5a, there remain a number of areas that are
      incompletely understood and therapeutic opportunities are still being evaluated.
      In this review, we summarise the cellular basis for C5a-induced vulnerability to
      nosocomial infection and organ dysfunction. We focus on cells of the innate
      immune system, highlighting the major areas in need of further research and
      potential avenues for targeted therapies.

PMID- 30229882
TI  - Sea Level Rise Cut in Half?

PMID- 30229881
TI  - Cutaneous collagenous vasculopathy induced by the vascular endothelial growth
      factor receptor inhibitor axitinib.

PMID- 30229883
TI  - A novel cognitive stress management technique for acne vulgaris: a short report
      of a pilot experimental study.
AB  - BACKGROUND: Acne vulgaris (AV) is one of the most common disorders treated by
      dermatologists and other healthcare providers. Stress is a well-attested
      contributor to AV pathogenesis. However, to our knowledge, stress management has
      not yet been performed in AV patients. In this 8-week experimental study, we
      primarily examined the effectiveness of a novel method, dubbed Pythagorean Self
      Awareness Intervention (PSAI) in AV. METHODS: This is a two-armed 1 : 1
      randomized non-blind experimental study. The total sample was comprised of 15
      female patients in the intervention group (mean age 27.2 +/- 6.6) and 15 female
      patients in the control group (mean age 29.1 +/- 6.9), all women. Measurements
      included clinical stage of AV, acne-related quality of life, perceived stress,
      and positive and negative affect assessed by validated self-administered tools.
      RESULTS: Fourteen (93.3%) patients in the intervention group and four (26.7%)
      patients in the control group showed improvement of the acne stage (relative
      risk: 3.5, 95% CI 1.5-8.2, P = 0.001). Significant improvements remained after
      adjusting for age and baseline acne stage. Large to moderate significant effects
      were observed for perceived stress and negative affect. There were no dropouts
      and side effects in the PSAI group, whereas compliance reached 100%. CONCLUSIONS:
      Pythagorean Self-Awareness Intervention is a feasible and possibly effective
      stress management method for AV. Future larger and longer randomized controlled
      studies are strongly encouraged.

PMID- 30229884
TI  - Variations in the provision and cost of oral healthcare in 11 European countries:
      a case study.
AB  - AIM: To compare the provision and costs at the point of delivery of dental
      treatments in a sample of European Union (EU) Member States. MATERIALS AND
      METHODS: A questionnaire with open-ended questions was sent to oral health policy
      makers in Denmark, England, France, Germany, Hungary, Ireland, Italy, the
      Netherlands, Poland, Romania, Scotland and Spain. They were asked to answer
      questions on the probable costs and provision of treatment in their country for a
      vignette presented as a pre-defined case. RESULTS: All respondents returned
      answers to all questions. Wide variations were reported in: who would deliver
      care, cost of items of care and total cost. For example, in France, only a
      dentist would provide the treatment. In Denmark, England, Germany, Ireland,
      Italy, the Netherlands and Scotland, it was likely that the treatment would be
      provided by a combination of dentist, dental hygienist and dental nurse. Fees
      ranged from ?72 in England (if treated within the NHS) to ?603 in Denmark. In
      Italy, Spain and for most patients in Romania, all treatment costs were paid by
      the patient. In the other nine countries, some subsidy from public funds was
      available. In terms of percentage of per capita Gross National Income, the cost
      to the patient ranged from 0.12% in France to 1.57% in Spain. CONCLUSIONS: It was
      apparent that there are wide variations between EU Member States in the manner in
      which oral healthcare is delivered, its cost and the extent to which the cost of
      treatment is subsidised from state funds or through private insurance.

PMID- 30229885
TI  - Variants in cardiac GATA genes associated with bicuspid aortic valve.
AB  - BACKGROUND: Bicuspid aortic valve (BAV) is a heterogeneous and still not fully
      understood condition, with diverse genetic aetiology and associated phenotypes
      ranging from aortic stenosis or regurgitation to aneurysm and dissection. Several
      genes have been associated with the presence of BAV, notably some members of the
      GATA family of transcription factors that play important roles in cardiac
      embryogenesis. METHODS: A case-control study with 122 unrelated and ethnically
      matched patients with bicuspid and 154 with tricuspid aortic valve was performed.
      All exons of GATA4, GATA5, and GATA6 genes were sequenced searching for variants.
      Frequencies were compared and functional effects of rare variants were analysed
      by informatic prediction tools. RESULTS: Four rare and potentially pathogenic
      variants were identified in only five sporadic cases: a missense p.Arg202Gln
      (rs782614097) in GATA5 and three synonymous variants, p.Cys274= (rs55980825) and
      p.His302= (rs201516339) in GATA4, and p.Asn458= (rs143026087) in GATA6. Minor
      alleles of p.His302=, p.Arg202Gln and rs3764962 are enriched in BAV patients
      compared to ExAC database (P = 0.01, 0.03, and 0.01 respectively). In addition, a
      common polymorphism in GATA5 (p.Asp203=, rs41305803) is associated with BAV
      showing a protective effect in carriers of the minor allele (OR [95%CI] =
      0.45[0.25-0.81]; P = 0.004). CONCLUSION: This study associates additional genetic
      variants in GATA4 and GATA5 with BAV, supporting the implication of these genes
      in the development of this valvulopathy. The discovery of all the genetic factors
      involved will contribute to a better understanding of the process and, therefore,
      to detect a genetic predisposition and even to the identification of therapeutic
      targets.

PMID- 30229886
TI  - Male competition drives song divergence along an ecological gradient in an avian
      ring species.
AB  - Sexual selection operates via female choice and male competition, which can act
      independently, in concert, or in opposition. Female choice is typically
      considered the stronger selective force, but how these two processes interact to
      shape phenotypic divergence is poorly understood. I tested the hypothesis that
      variation in sexual selection in different habitats drives song divergence in the
      greenish warbler ring species. I evaluated the strength, direction, and targets
      of female choice and male competition in three populations spanning 2400 km of
      latitude. Average song length increased with latitude, concomitant with a decline
      in population density. Within populations, males sang longer songs when females
      were fertile and shorter songs during territory establishment. Females
      consistently preferred males with longer songs and larger song repertoires. By
      contrast, playback experiments showed that males used short songs in territory
      defense. Songs were shortest at high densities, and in the highest density
      population only, song traits preferred by females correlated with male
      territoriality. Stronger male competition at high population densities likely
      constrains maximum song length, whereas weaker competition at low densities
      allows expression of female choice for long songs. Interactions between male
      competition and ecology may be a crucial but oft-overlooked component of
      phenotypic divergence and speciation.

PMID- 30229887
TI  - Certified testosterone immunoassays for hyperandrogenaemia.
AB  - BACKGROUND: Testosterone (T) measurement in women is problematic leading to
      initiatives aiming to improve laboratory standardization of commercial assays. We
      assessed the impact on the clinical diagnosis of functional hyperandrogenic
      disorders of a total T immunoassay recently certified by the Centers for Diseases
      Control and Prevention (CDC). METHODS: We conducted a cross-sectional study
      including 263 consecutive adult premenopausal women presenting with functional
      ovarian hyperandrogenism-including polycystic ovary syndrome (PCOS)-and 73
      nonhyperandrogenic female volunteers who served to define reference ranges. Total
      T was measured by a local routine direct radioimmunoassay and by a CDC-certified
      immunochemiluminescence assay. The main outcome measures were total and
      calculated free T concentrations and percentage of patients with
      hyperandrogenaemia. RESULTS: Both assays showed a poor concordance for total and
      calculated free T measurements. Hence, 147 (56%) and 109 (41%) of women had
      hyperandrogenaemia with the routine and CDC-certified assays, respectively [kappa
      (95%CI): 0.538 (0.441-0.634)]. Free T levels calculated from total T using both
      assays showed similar correlations with metabolic variables. Women showing
      hyperandrogenaemia by both methods had the worst metabolic profiles, yet women
      presenting with hyperandrogenaemia only when using the CDC-certified assay did
      not show any significant difference compared to nonhyperandrogenic women in
      anthropometric or metabolic variables. Those women with hyperandrogenaemia only
      when using the routine assay were more obese and insulin resistant than
      normoandrogenaemic hirsute patients. CONCLUSIONS: An isolated androgen
      measurement, even a very specific one, is unlikely to identify the
      hyperandrogenic milieu that characterizes patients with functional ovarian
      hyperandrogenism and PCOS.

PMID- 30229888
TI  - Predicting risk for seroma development after axillary or inguinal sentinel lymph
      node biopsy in melanoma patients.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) is currently a routine procedure in
      the staging of patients with cutaneous melanoma; however, little information is
      available about the risk factors for postoperative complications, especially for
      the risk of seroma formation. METHODS: Medical records of patients undergoing
      SLNB at the University Hospital of Cologne, Germany, between 2011 and 2016, were
      reviewed. Binary logistic regression was used to analyze the influence of a wide
      range of variables on seroma development. RESULTS: A total of 615 patients were
      included in the study. Overall, 20.4% of patients developed complications with
      seroma being the most common postoperative complication. Development of seroma
      was significantly more common among smokers than nonsmokers (OR = 1.956, P =
      0.007). Inguinal localization (OR = 3.644, P < 0.0001) was also associated with
      seroma formation. Male patients developed a seroma significantly more often than
      female patients following SLNB (OR = 2.104, P = 0.001). The presence or absence
      of metastasis in the lymph node did not influence seroma development.
      CONCLUSIONS: Male sex, inguinal localization, and smoking are risk factors for
      the development of seroma.

PMID- 30229889
TI  - Lymphoepithelioma-like carcinoma of the skin: a possible culprit when biopsy
      indicates a benign inflammatory reaction.

PMID- 30229890
TI  - The Association between Symptom Accommodation and Emotional Coregulation in
      Couples with Binge Eating Disorder.
AB  - Intense negative emotions and maladaptive behavioral strategies to reduce
      emotional distress occur not only in patients with various forms of
      psychopathology but also in their committed partners. One common strategy to
      reduce distress is for partners to accommodate to the symptoms of the disorder,
      which reduces distress short term but maintains symptoms long term. Accommodation
      is believed to be motivated by the partner reacting behaviorally to the patient's
      emotions, but the emotions of the partner in this context have yet to be
      examined. This pilot study examined how partner accommodation related to specific
      patterns of emotional coregulation between patients with binge eating disorder
      (BED) and their partners, before and after a couple-based intervention for BED.
      Vocally encoded emotional arousal was measured during couples' (n = 11)
      conversations about BED. As predicted, partners' emotional reactivity to
      patients' emotional arousal was associated with high accommodation before
      treatment. Thus, partners may use accommodation as a strategy to reduce both the
      patients' and their own distress. After treatment, partners' arousal was no
      longer associated with the patients' emotional arousal; instead, partners showed
      greater emotional stability over time, specifically when accommodation was low.
      Additionally, patients were less emotionally aroused after treatment. Therefore,
      treatment may have decreased overall emotionality of patients and altered the
      association between accommodation and partners' emotional reactivity. If
      replicated, this understanding of the emotional context associated with
      accommodation in BED can inform couple-based treatment by targeting specific
      emotional precipitants of behaviors that maintain symptoms.

PMID- 30229892
TI  - Relationship Distress as a Mediator of Adverse Childhood Experiences and Health:
      Implications for Clinical Practice with Economically Vulnerable Racial and Ethnic
      Minorities.
AB  - Adverse childhood experiences (ACE) are interpersonal sources of distress
      negatively correlated with physical and mental health, as well as maladaptive
      intimate partner conflict strategies in adulthood. Economically vulnerable racial
      and ethnic minorities report the greatest disparities in exposure to ACE, as well
      as relationship distress and health. Yet, little is known about the connections
      between ACE, relationship distress, and health. We therefore tested a theoretical
      model for the mediating role of relationship distress to explain the ACE-health
      connection with a sample (N = 96) predominantly racial/ethnic minorities (87%)
      with low income. We applied partial least squares structural equation modeling
      with bootstrapping (N = 500). Relationship distress strengthened the predictive
      relationship between ACE and health, and accounted for 42% of the variance in
      health. The results provide preliminary support for relationship distress as a
      social determinant of health disparities with implications for interdisciplinary
      health intervention.

PMID- 30229893
TI  - Expression and significance of phosphodiesterase 4B gene in peripheral blood of
      patients with oral lichen planus.
AB  - BACKGROUND: The pathogenesis of oral lichen planus (OLP) may be related to mental
      factors. In this study, we investigated the molecular mechanism of mental factors
      in the development of OLP. METHODS: The normal control group and OLP patients
      were tested and evaluated by Zung self-rating anxiety scale and self-rating
      depression scale. Secondly, Agilent human LncRNA chip technology was used to
      detect differential genes in the total RNA of the normal control group and OLP
      patients, and to screen out the differentially expressed genes related to anxiety
      and depression. Thirdly, we verified the genes at gene level and protein level,
      respectively. RESULTS: Zung self-rating anxiety scale and self-rating depression
      scale showed that tendency of anxiety and depression in OLP patients is
      significantly higher than that in normal controls, but there was no significant
      difference between the erosion form group and the reticular form group; the
      duration of OLP showed significant negative correlations between degree of
      anxiety and depression. Microarray analysis showed there were four differential
      genes (PDE4B, RGS2, SYNGR1, and SYNE1) related to anxiety and depression in OLP
      patients; real-time qPCR confirmed the expression of PDE4B mRNA was lower in the
      peripheral blood of normal control group (P < 0.001). The expression of RGS2,
      SYNGR1, and SYNE1 mRNA was higher in the normal control group (P < 0.05, P <
      0.05, P < 0.05). Wes automatic western blot confirmed that the expression of
      PDE4B protein was lower in the peripheral blood of the normal control group (P <
      0.01). CONCLUSION: PDE4B gene may play a role in the pathogenesis of OLP.

PMID- 30229891
TI  - Properties and functions of adipose tissue macrophages in obesity.
AB  - The expansion of adipose tissue (AT) in obesity is accompanied by the
      accumulation of immune cells that contribute to a state of low-grade, chronic
      inflammation and dysregulated metabolism. Adipose tissue macrophages (ATMs)
      represent the most abundant class of leukocytes in AT and are involved in the
      regulation of several regulatory physiological processes, such as tissue
      remodeling and insulin sensitivity. With progressive obesity, ATMs are key
      mediators of meta-inflammation, insulin resistance and impairment of adipocyte
      function. While macrophage recruitment from blood monocytes is a critical
      component of the generation of AT inflammation, new studies have revealed a role
      for ATM proliferation in the early stages of obesity and in sustaining AT
      inflammation. In addition, studies have revealed a more complex range of
      macrophage activation states than the previous M1/M2 model, and the existence of
      different macrophage profiles between human and animal models. This review will
      summarize the current understanding of the regulatory mechanisms of ATM function
      in relation to obesity, type 2 diabetes, depot of origin, and to other leukocytes
      such as AT dendritic cells, with hopes of emphasizing the regulatory nodes that
      can potentially be targeted to prevent and treat obesity-related metabolic
      disorders.

PMID- 30229894
TI  - Prevalence and risk factors for urinary tract infection following stress urinary
      incontinence surgery with two midurethral sling procedures.
AB  - OBJECTIVE: To compare prevalence and risk factors for urinary tract infection
      (UTI) following midurethral sling surgery with either the GYNECARE ABBREVO
      Continence System (Ethicon, Somerville, NJ, USA) or a standard transobturator.
      METHODS: A retrospective cohort study was conducted among women who underwent
      midurethral sling surgery to treat stress urinary incontinence at a single
      tertiary hospital in Israel between January 1, 2014, and August 11, 2015. Data
      were retrieved from medical records. The diagnosis of UTI was based on a positive
      urine culture result. RESULTS: Of 178 patients included, 30 (16.9%) underwent the
      ABBREVO procedure and 148 (83.1%) underwent the standard transobturator
      procedure. The mean +/- SD BMI at the time of surgery was 28.1 +/- 4.5 for the
      standard transobturator procedures and 30.7 +/- 15.2 for the ABBREVO procedures.
      Women who underwent the ABBREVO procedure had an increased duration of
      hospitalization (P=0.004), and higher rates of concomitant anterior colporrhaphy
      procedures (P=0.009) and concomitant hysterectomy (P=0.009). Only 38 (21.3%)
      women developed UTIs within 12 months of surgery (seven in the ABBREVO procedure
      group and 31 in the standard transobturator procedure group). No statistically
      significant between-group differences were found for the risk of UTI or for
      urinary tract adverse events, such as recurrent UTI and the need for
      rehospitalization. CONCLUSIONS: The two procedures were comparable in terms of
      prevalence and risk factors for UTI during the postoperative period.

PMID- 30229896
TI  - Near-fatal Intoxication with the "New" Synthetic Opioid U-47700: The First
      Reported Case in the Czech Republic.
AB  - Recreational use of the potent synthetic opioid 3,4- dichloro-N-(2
      (dimethylamino)cyclohexyl)-N-methylbenzamide (U-47700) is rising, accompanied by
      increasingly frequent cases of serious intoxication. This article reports a case
      of near-fatal U-47700 intoxication. A man was found unconscious (with drug powder
      residues). After 40 h in hospital (including 12 h of supported ventilation), he
      recovered and was discharged. Liquid chromatography/high-resolution mass
      spectrometry (LC/HRMS) or gas chromatography/mass spectrometry (GC/MS) were used
      to detect and quantify substances in powders, serum and urine. Powders contained
      U-47700 and two synthetic cannabinoids. Serum and urine were positive for U-47700
      (351.0 ng/mL), citalopram (<LOQ), tetrahydrocannabinol (THC: 3.3 ng/mL),
      midazolam (<LOQ) and a novel benzodiazepine, clonazolam (6.8 ng/mL) and their
      metabolites but negative for synthetic cannabinoids. If potent synthetic opioids
      become cheaper and more easily obtainable than their classical counterparts
      (e.g., heroin), they will inevitably replace them and users may be exposed to
      elevated risks of addiction and overdose.

PMID- 30229897
TI  - Single-cell genetic analysis of clonal dynamics in colorectal adenomas indicates
      CDX2 gain as a predictor of recurrence.
AB  - Colorectal adenomas are common precancerous lesions with the potential for
      malignant transformation to colorectal adenocarcinoma. Endoscopic polypectomy
      provides an opportunity for cancer prevention; however, recurrence rates are
      high. We collected formalin-fixed paraffin-embedded tissue of fifteen primary
      adenomas with recurrence, fifteen adenomas without recurrence, and fourteen
      matched pair samples (primary adenoma and the corresponding recurrent adenoma).
      The samples were analysed by array-comparative genomic hybridisation (aCGH) and
      single-cell multiplex-interphase fluorescence in situ hybridisation (miFISH) to
      understand clonal evolution, to examine the dynamics of copy number alterations
      (CNAs) and to identify molecular markers for recurrence prediction. The miFISH
      probe panel consisted of fourteen colorectal carcinogenesis-relevant genes (COX2,
      PIK3CA, APC, CLIC1, EGFR, MYC, CCND1, CDX2, CDH1, TP53, HER2, SMAD7, SMAD4 and
      ZNF217), and a centromere probe (CEP10). ACGH analysis confirmed the genetic
      landscape typical for colorectal tumorigenesis, i.e., CNAs of chromosomes 7, 13q,
      18 and 20q. Focal aberrations (<=10 Mbp) were mapped to chromosome bands 6p22.1
      p21.33 (33.3%), 7q22.1 (31.4%) and 16q21 (29.4%). MiFISH detected gains of EGFR
      (23.6%), CDX2 (21.8%) and ZNF217 (18.2%). Most adenomas exhibited a major clone
      population which was accompanied by multiple smaller clone populations. Gains of
      CDX2 were exclusively seen in primary adenomas with recurrence (25%) compared to
      primary adenomas without recurrence (0%). Generation of phylogenetic trees for
      matched pair samples revealed four distinct patterns of clonal dynamics. In
      conclusion, adenoma development and recurrence are complex genetic processes
      driven by multiple CNAs whose evaluation by miFISH, with emphasis on CDX2, might
      serve as predictor of recurrence. This article is protected by copyright. All
      rights reserved.

PMID- 30229898
TI  - Melatonin and pancreatic cancer: Current knowledge and future perspectives.
AB  - Pancreatic cancer has a high mortality rate due to the absence of early symptoms
      and subsequent late diagnosis; additionally, pancreatic cancer has a high
      resistance to radio- and chemotherapy. Multiple inflammatory pathways are
      involved in the pathophysiology of pancreatic cancer. Melatonin an indoleamine
      produced in the pineal gland mediated and receptor-independent action is the
      pancreas and other where has both receptors. Melatonin is a potent antioxidant
      and tissue protector against inflammation and oxidative stress. In vivo and in
      vitro studies have shown that melatonin supplementation is an appropriate
      therapeutic approach for pancreatic cancer. Melatonin may be an effective
      apoptosis inducer in cancer cells through regulation of a large number of
      molecular pathways including oxidative stress, heat shock proteins, and vascular
      endothelial growth factor. Limited clinical studies, however, have evaluated the
      role of melatonin in pancreatic cancer. This review summarizes what is known
      regarding the effects of melatonin on pancreatic cancer and the mechanisms
      involved.

PMID- 30229899
TI  - MicroRNA-363 inhibits angiogenesis, proliferation, invasion, and migration of
      renal cell carcinoma via inactivation of the Janus tyrosine kinases 2-signal
      transducers and activators of transcription 3 axis by suppressing growth hormone
      receptor gene.
AB  - Renal cell carcinoma (RCC) is the most common malignancy involving the kidneys
      and a major cause of cancer mortality. The involvement of microRNA (miRNA)
      expression in the tumorigenesis and progression of RCC has been previously
      highlighted. Therefore, we conducted this study to investigate whether microRNA
      363 (miR-363) affects the development of RCC via the Janus tyrosine kinases
      (JAK2)-signal transducers and activators of transcription (STAT) axis by
      targeting the growth hormone receptor (GHR), by observing the changes that
      occurred in the RCC and the normal adjacent tissues of patients with RCC. RCC
      cells were transfected with a series of miR-363 mimic, miR-363 inhibitor, or
      small interfering RNA against GHR to determine the influence of miR-363 on the
      expression of GHR and JAK2-STAT3 axis-related genes with the use of reverse
      transcription quantitative polymerase chain reaction and Western blot analysis.
      The angiogenesis, viability, invasion, and migration of cells were evaluated by
      means of in vitro angiogenesis, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di
      phenytetrazoliumromide (MTT), wound-healing, and Transwell assays. The results
      revealed reduced miR-363 expression and elevated GHR expression in RCC. It was
      also found that miR-363 altered the activation of the JAK2-STAT3 axis through the
      inhibition of GHR. Cells treated with the miR-363 inhibitor presented with
      increased capillary vessels, cell viability, invasion, and migration, whereas it
      was on the contrary in the RCC cells with overexpressed miR-363. These results
      implicated that the overexpression of miR-363 could specifically bind to GHR to
      downregulate the expression of GHR, which, in turn, inactivates the JAK2-STAT3
      axis, thereby influencing the angiogenesis, cell invasion, and migration
      abilities in RCC.

PMID- 30229900
TI  - Comparison of UVB effects on growth and induction of UVB screening compounds in
      isolates of metaphytic algae from temperate zone streams and ponds.
AB  - Filaments in the surface layers of metaphytic mats are exposed to high photon
      flux densities of PAR and UVBR. We investigated the effect of UVBR exposure on
      growth of eight isolates of common metaphytic algae (Cladophora, Mougeotia,
      Oedogonium, Pithophora, Spirogyra, and Zygnema) acclimated to either high or low
      PAR levels prior to UVBR exposure. All isolates acclimated to low PAR exhibited
      significant reductions in growth rate caused by the UVBR exposure (P < 0.05).
      Acclimation to high PAR resulted in seven of the isolates being more tolerant of
      the UVB exposure. The two Zygnema isolates exhibited the most pronounced effect
      of high PAR acclimation with growth rates of UVB exposed treatments being equal
      to that of controls (P > 0.05). High PAR acclimation also protected chlorophyll a
      levels in the Zygnema isolates. Absorption of UVB by methanol extracts increased
      322%-381% for the two Zygnema isolates when high PAR acclimated. The broad
      absorption peak at 270 nm suggests that phenolic compounds were responsible.
      Previous studies have shown that Zygnema isolates from extreme environments
      tolerate UVBR and contain UVB screening compounds, but our results extend these
      adaptions to Zygnema from typical temperate zone habitats. Although none of the
      other metaphytic algae produced UVB absorbing compounds, they all exhibited
      higher growth rates under UVBR exposure following high PAR acclimation. This
      suggests that the algae evaluated have inducible defenses against UVBR exposure
      that coupled with their mat structure would provide an adaption to the
      challenging light environment in shallow-water habitats.

PMID- 30229901
TI  - Association between glucose-lowering treatment and cancer metastasis among
      patients with preexisting type 2 diabetes and incident malignancy.
AB  - Preclinical data suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors may
      promote metastatic progression of preexisting cancer via nuclear factor erythroid
      2 related factor 2 (NRF2) activation. We aimed to investigate the association
      between different glucose-lowering treatments, including DPP-4 inhibitors and
      metformin, both with potential NRF2 modulating effects, and new-onset metastatic
      cancer among type 2 diabetes patients with comorbid incident cancer. This
      population-based cohort study included 223,530 diabetic patients newly diagnosed
      with primary cancer during 2009-2011 in Korea. The patients were categorized into
      five study cohorts in accordance with treatment modalities during the follow-up
      until the end of 2016: no-antidiabetic drugs (no-AD), metformin, DPP-4
      inhibitors, metformin+DPP-4 inhibitors, and insulin treatment. Following
      propensity score (PS) matching in a 1:1 ratio against the no-AD group, 18,805
      patients in metformin, 1,865 in DPP-4 inhibitors, 31,074 in metformin+DPP-4
      inhibitors, and 1,895 patients in insulin groups were identified for cohort entry
      and analyzed against the corresponding number of no-AD patients in each PS
      matched comparison pair. Metastatic risk was lower with metformin plus or minus
      DPP-4 inhibitors (HR 0.84, 95% CI 0.79-0.90 and 0.87, 0.80-0.95, respectively),
      not significantly associated with DPP-4 inhibitors (0.99, 0.77-1.29) except after
      thyroid cancer (3.89, 1.01-9.64), and higher with insulin therapy (1.81, 1.46
      2.24) compared with no-AD use for all cancers combined. In conclusion, DPP-4
      inhibitor therapy was not associated with significant risk of cancer metastasis
      relative to no-AD therapy, irrespective of patient age and sex, except after
      thyroid cancer, while metastatic risk was decreased with metformin treatment
      among type 2 diabetes patients with preexisting cancer. This article is protected
      by copyright. All rights reserved.

PMID- 30229895
TI  - BRAZIL ROAD-KILL: a data set of wildlife terrestrial vertebrate road-kills.
AB  - Mortality from collision with vehicles is the most visible impact of road traffic
      on wildlife. Mortality due to roads (hereafter road-kill) can affect the dynamic
      of populations of many species and can, therefore, increase the risk of local
      decline or extinction. This is especially true in Brazil, where plans for road
      network upgrading and expansion overlaps biodiversity hotspot areas, which are of
      high importance for global conservation. Researchers, conservationists and road
      planners face the challenge to define a national strategy for road mitigation and
      wildlife conservation. The main goal of this dataset is a compilation of geo
      referenced road-kill data from published and unpublished road surveys. This is
      the first Data Paper in the BRAZIL series (see ATLANTIC, NEOTROPICAL, and BRAZIL
      collections of Data Papers published in Ecology), which aims make public road
      kill data for species in the Brazilian Regions. The dataset encompasses road-kill
      records from 45 personal communications and 26 studies published in peer-reviewed
      journals, theses and reports. The road-kill dataset comprises 21,512 records, 83%
      of which are identified to the species level (n = 450 species). The dataset
      includes records of 31 amphibian species, 90 reptile species, 229 bird species,
      and 99 mammal species. One species is classified as Endangered, eight as
      Vulnerable and twelve as Near Threatened. The species with the highest number of
      records are: Didelphis albiventris (n = 1,549), Volatinia jacarina (n = 1,238),
      Cerdocyon thous (n = 1,135), Helicops infrataeniatus (n = 802), and Rhinella
      icterica (n = 692). Most of the records came from southern Brazil. However,
      observations of the road-kill incidence for non-Least Concern species are more
      spread across the country. This dataset can be used to identify which taxa seems
      to be vulnerable to traffic, analyze temporal and spatial patterns of road-kill
      at local, regional and national scales and also used to understand the effects of
      road-kill on population persistence. It may also contribute to studies that aims
      to understand the influence of landscape and environmental influences on road
      kills, improve our knowledge on road-related strategies on biodiversity
      conservation and be used as complementary information on large-scale and
      macroecological studies. No copyright or proprietary restrictions are associated
      with the use of this data set other than citation of this Data Paper.

PMID- 30229902
TI  - Pyruvate dehydrogenase kinase 1 contributes to cisplatin resistance of ovarian
      cancer through EGFR activation.
AB  - Patients with ovarian cancer frequently develop acquired drug resistance after
      the long-term chemotherapy, leading to disease progression. Enhanced epithelial
      mesenchymal transition (EMT) has been implicated in chemoresistance of ovarian
      cancer cells; however, the molecular mechanisms involved are largely undefined.
      Pyruvate dehydrogenase kinase 1 (PDK1), a key regulatory enzyme in glucose
      metabolism, has been recognized as a gatekeeper of the Warburg effect, a hallmark
      of cancer. In this study, the function of PDK1 in cisplatin resistance of ovarian
      cancer in terms of growth and EMT was investigated. PDK1 was upregulated in
      cisplatin-resistant ovarian cancer cells. PDK1 knockdown in resistant cells led
      to increased sensitivity to cisplatin-induced cell death and apoptosis. PDK1
      downregulation also reversed the EMT and cell motility in cisplatin-resistant
      cells. In a mouse xenograft model, tumors derived from PDK1-silenced ovarian
      cancer cells exhibited decreased tumor growth and EMT compared with control after
      the cisplatin treatment. Mechanistically, PDK1 overexpression led to increased
      phosphorylation of EGFR, and blocking EGFR kinase activity by erlotinib reversed
      cisplatin resistance induced by PDK1 overexpression. Furthermore, in patients
      with ovarian cancer, higher PDK1 and p-EGFR levels were associated with
      chemoresistance. These results supported that PDK1 contributes to chemoresistance
      of ovarian cancer by activating EGFR. Therefore, PDK1 may serve as a promising
      target to combat chemoresistance of ovarian cancer.

PMID- 30229904
TI  - Ochronosis Presenting as Methemoglobinemia.
AB  - Ochronosis is the blue-gray discoloration of collagen-containing tissues due to
      homogentisic acid (HGA) deposition, secondary to endogenous alkaptonuria or
      exogenous enzyme inhibition. In renal disease, accumulation of HGA in serum can
      cause methemoglobinemia. A 60-year-old woman with renal disease and anemia
      presented with 3 days of weakness and months of gray skin discoloration. Her
      hemoglobin was 8.1g/dl with 24.5% methemoglobin. Despite treatment with methylene
      blue, exchange transfusion, and continuous renal replacement therapy, the patient
      died. Autopsy revealed gray discoloration and ochronotic pigment in the ribs and
      cartilage. Based on these findings, the patient was diagnosed with ochronosis,
      suggestive of alkaptonuria, complicated by methemoglobinemia. The differential
      diagnosis for blue-gray skin discoloration includes argyria, methemoglobinemia,
      and ochronosis. This patient's clinical and autopsy findings suggested
      alkaptonuria complicated by methemoglobinemia due to progressive renal
      dysfunction. Development of methemoglobinemia in the setting of chronic skin
      discoloration and renal failure should prompt consideration of alkaptonuria.

PMID- 30229905
TI  - Egg Yolk Extracts as Potential Liposomes Shell Material: Composition Compared
      with Vesicles Characteristics.
AB  - : Our aim was to propose simple extraction process to obtain phospholipids along
      with yolk-derived vitamins and fats. Five extracts marked as ethanol/acetone,
      methanol-chloroform/acetone, hot ethanol, hexane, and cold ethanol were developed
      and compared. Extracts' compositions were analyzed in terms of phospholipid,
      polar and nonpolar fraction, cholesterol, carotenoids, and tocopherols content.
      Further, liposomes prepared from extracts were characterized. The highest
      extraction efficiency was achieved by a one-step hexane procedure. However, that
      sample, in contrast to the other four extracts, revealed distinctively lower
      permeability when used for liposomes membrane formation. Principal component
      analysis proved that major components contents were decisive for liposomes
      membranes permeability, whereas minor constituents' content controlled zeta
      potential and Z-average size. PRACTICAL APPLICATION: Liposomes are nanocarriers
      widely used in pharmaceutical industry. Due to intravenous route of
      administration, they have to be produced from phospholipids of very fine purity.
      On the other hand, there is increasing interest in nanoencapsulation of labile,
      bioactive substances for manufacturing of health promoting food. Unfortunately,
      high-price pure phospholipids are prohibitive for food applications. The use of
      raw material obtained by simple extraction procedure instead of highly purified
      phospholipids could be an attractive alternative for food industry.

PMID- 30229903
TI  - Pancreatic cancer and autoimmune diseases: An association sustained by
      computational and epidemiological case-control approaches.
AB  - Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its
      associated multimorbidities will enhance our knowledge toward PC control. The
      study investigated the common genetic background of PC and different morbidities
      through a computational approach and further evaluated the less explored
      association between PC and autoimmune diseases (AIDs) through an epidemiological
      analysis. Gene-disease associations (GDAs) of 26 morbidities of interest and PC
      were obtained using the DisGeNET public discovery platform. The association
      between AIDs and PC pointed by the computational analysis was confirmed through
      multivariable logistic regression models in the PanGen European case-control
      study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared
      at least one gene with PC in the DisGeNET database. Based on common genes,
      several AIDs were genetically associated with PC pointing to a potential link
      between them. An epidemiologic analysis confirmed that having any of the nine
      AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio
      (OR) = 0.74, 95% confidence interval (CI) 0.58-0.93) which decreased in subjects
      having >=2 AIDs (OR = 0.39, 95%CI 0.21-0.73). In independent analyses,
      polymyalgia rheumatica, and rheumatoid arthritis were significantly associated
      with low PC risk (OR = 0.40, 95%CI 0.19-0.89, and OR = 0.73, 95%CI 0.53-1.00,
      respectively). Several inflammatory-related morbidities shared a common genetic
      component with PC based on public databases. These molecular links could shed
      light into the molecular mechanisms underlying PC development and simultaneously
      generate novel hypotheses. In our study, we report sound findings pointing to an
      association between AIDs and a reduced risk of PC.

PMID- 30229906
TI  - A critical role of the transient receptor potential melastatin 2 channel in a
      positive feedback mechanism for reactive oxygen species-induced delayed cell
      death.
AB  - Transient receptor potential melastatin 2 (TRPM2) channel activation by reactive
      oxygen species (ROS) plays a critical role in delayed neuronal cell death,
      responsible for postischemia brain damage via altering intracellular Zn2+
      homeostasis, but a mechanistic understanding is still lacking. Here, we showed
      that H2 O2 induced neuroblastoma SH-SY5Y cell death with a significant delay,
      dependently of the TRPM2 channel and increased [Zn2+ ]i , and therefore used this
      cell model to investigate the mechanisms underlying ROS-induced TRPM2-mediated
      delayed cell death. H2 O2 increased concentration-dependently the [Zn2+ ]i and
      caused lysosomal dysfunction and Zn2+ loss and, furthermore, mitochondrial Zn2+
      accumulation, fragmentation, and ROS generation. Such effects were suppressed by
      preventing poly(adenosine diphosphate ribose, ADPR) polymerase-1-dependent TRPM2
      channel activation with PJ34 and 3,3',5,5'-tetra-tert-butyldiphenoquinone,
      inhibiting the TRPM2 channel with 2-aminoethoxydiphenyl borate (2-APB) and N-(p
      amylcinnamoyl)anthranilic acid, or chelating Zn2+ with N,N,N,N-tetrakis(2
      pyridylmethyl)-ethylenediamine (TPEN). Bafilomycin-induced lysosomal dysfunction
      also resulted in mitochondrial Zn2+ accumulation, fragmentation, and ROS
      generation that were inhibited by PJ34 or 2-APB, suggesting that these
      mitochondrial events are TRPM2 dependent and sequela of lysosomal dysfunction.
      Mitochondrial TRPM2 expression was detected and exposure to ADPR-induced Zn2+
      uptake in isolated mitochondria, which was prevented by TPEN. H2 O2 -induced
      delayed cell death was inhibited by apocynin and diphenyleneiodonium,
      nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase (NOX)
      inhibitors, GKT137831, an NOX1/4-specific inhibitor, or Go6983, a protein kinase
      C (PKC) inhibitor. Moreover, inhibition of PKC/NOX prevented H2 O2 -induced ROS
      generation, lysosomal dysfunction and Zn2+ release, and mitochondrial Zn2+
      accumulation, fragmentation and ROS generation. Collectively, these results
      support a critical role for the TRPM2 channel in coupling PKC/NOX-mediated ROS
      generation, lysosomal Zn2+ release, and mitochondrial Zn2+ accumulation, and ROS
      generation to form a vicious positive feedback signaling mechanism for ROS
      induced delayed cell death.

PMID- 30229907
TI  - The Formation of Acrylamide from and Its Reduction by 3-Aminopropanamide Occur
      Simultaneously During Thermal Treatment.
AB  - : 3-Aminopropanamide (3-APA) is the direct precursor of acrylamide produced in
      the Maillard reaction between asparagine and reducing sugars. In this research,
      we found that 3-APA could reduce acrylamide by the formation of adducts between
      acrylamide and 3-APA via Michael addition. The effects of temperature, heating
      duration and 3-APA/acrylamide ratio on the reduction of acrylamide were
      investigated. Addition of 3-APA to acrylamide at a molar ratio of 5:3 at 160 
      degrees C for 20 min reduced acrylamide by up to 47.29%. The major adduct was
      identified as 3,3',3'-nitrilotris, and its cytotoxicity on Caco-2 cells was
      evaluated to be much lower than acrylamide. The viability of Caco-2 cells
      retained at 88.31% and 86.43% after incubation with 16 mM 3,3',3'-nitrilotris for
      24 and 48 hr, respectively, while those incubated with the same concentration of
      acrylamide were 23.33% and 19.12%, respectively. PRACTICAL APPLICATION: The
      current study reported 3-APA could reduce acrylamide through the Micheal addition
      reaction between 3-APA and acrylamide. The adduct showed significantly reduced
      cytotoxicity compared to acrylamide. The research is critical in evaluation and
      control of food contaminants. The results brought new insights in the area of
      food safety, especially in the mechanism researches on formation and mitigation
      of endogenous contaminants in thermal-processed foods.

PMID- 30229908
TI  - New advances of lncRNAs in liver fibrosis, with specific focus on lncRNA-miRNA
      interactions.
AB  - Noncoding RNAs (ncRNAs) were initially thought to be transcriptional byproducts.
      However, recent advances of ncRNAs research have increased our understanding of
      the importance of ncRNA in gene regulation and disease pathogenesis. Consistent
      with these developments, liver fibrosis research is also experiencing rapid
      growth in the investigation of links between ncRNAs and the pathology of this
      disease. The initial focus was on studying the function and regulation mechanisms
      of microRNAs (miRNAs). However, recently, elucidation of the mechanisms of long
      noncoding RNAs (lncRNAs) and lncRNA-mediated liver fibrosis has just commenced.
      In this review, we emphasize on abnormal expression of lncRNAs in liver fibrosis.
      Furthermore, we also discuss that the interaction of lncRNAs with miRNAs is
      involved in the regulation of the expression of protein-coding genes in liver
      fibrosis. Recent advances in understanding dysregulated lncRNAs expression and
      the lncRNAs-miRNAs interaction in liver fibrosis will help for developing new
      therapeutic targets and biomarkers of liver fibrosis.

PMID- 30229910
TI  - Synthesis of new anticancer and anti-inflammatory isoxazolines and aziridines
      from the natural (-)-deltoin.
AB  - OBJECTIVES: This work describes the synthesis, the bioactivity and the structure
      activity relationship of new derivatives from a natural coumarin. METHODS: (-)
      Deltoin 1 and the corresponding isoxazolines and aziridines were characterized by
      spectroscopic means. The cytotoxic (HTC-116, IGROV-1 and OVCAR-3 cancer cell
      lines) and 5-lipoxygenase activity of (-)-deltoin 1 and its structural analogues
      have been evaluated. KEY FINDINGS: The phytochemical investigation of the ethyl
      acetate extract of the flowers of Ferula lutea (Poir.) Maire has led to the
      isolation of (-)-deltoin 1. A series of new isoxazoline 2a,a'-2f,f' and aziridine
      3a,a'-3e,e' derivatives have been prepared by 1,3-dipolar cycloaddition. It has
      been found that the derivatives 2a (IC50 = 3.3 +/- 0.1 MUm), 3a,a' (IC50 = 5.9 +/
      0.1 MUm), 3b,b' (IC50 = 6.1 +/- 0.7 MUm) and 3c,c' (IC50 = 7.3 +/- 0.9 MUm)
      bearing a phenyl isoxazoline, a phenylaziridine, a 4-methlphenylaziridine and a 4
      methoxyphenylaziridine, respectively, are more cytotoxic than (-)-deltoin 1 (IC50
      = 14.3 +/- 0.2 MUm). The diastereoisomers in mixture (2f,f') with a 6
      chloropyridin-2-yl system have shown the best anti-5-lipoxygenase activity (%
      inhibition = 53.1 +/- 4.8% at 200 MUm). CONCLUSIONS: Some analogues have been
      found more bioactive than deltoin 1. Their activity has been related to the
      nature of the added heterocycles. It would be interesting to evaluate their in
      vivo activity.

PMID- 30229909
TI  - Primordial germ cells as a potential shared cell of origin for mucinous cystic
      neoplasms of the pancreas and mucinous ovarian tumors.
AB  - Mucinous ovarian tumors (MOTs) morphologically and epidemiologically resemble
      mucinous cystic neoplasms (MCNs) of the pancreas, sharing a similar stroma and
      both occurring disproportionately among young females. Additionally, MOTs and
      MCNs share similar clinical characteristics and immunohistochemical phenotypes.
      Exome sequencing has revealed frequent recurrent mutations in KRAS and RNF43 in
      both MOTs and MCNs. The cell of origin for these tumors remains unclear, but MOTs
      sometimes arise in the context of mature cystic teratomas and other primordial
      germ cell (PGC) tumors. We undertook the present study to investigate whether non
      teratoma-associated MOTs and MCNs share a common cell of origin. Comparisons of
      the gene expression profiles of MOTs [including both the mucinous borderline
      ovarian tumors (MBOTs) and invasive mucinous ovarian carcinomas (MOCs)], high
      grade serous ovarian carcinomas, ovarian surface epithelium, Fallopian tube
      epithelium, normal pancreatic tissue, pancreatic duct adenocarcinomas, MCNs, and
      single-cell RNA-sequencing of PGCs revealed that both MOTs and MCNs are more
      closely related to PGCs than to either eutopic epithelial tumors or normal
      epithelia. We hypothesize that MCNs may arise from PGCs that stopped in the
      dorsal pancreas during their descent to the gonads during early human
      embryogenesis, while MOTs arise from PGCs in the ovary. Together, these data
      suggest a common pathway for the development of MCNs and MOTs, and suggest that
      these tumors may be more properly classified as germ cell tumor variants.
      Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 30229912
TI  - Do demographic disparities exist in the diagnosis and surgical management of
      otitis media?
AB  - OBJECTIVE: Determine if demographic disparities exist between the diagnosis of
      otitis media (OM) and the provision of myringotomy and tubes in children. STUDY
      DESIGN: Cross-sectional analysis of a national database. METHODS: The National
      Ambulatory Medical Care Survey 2010 and the National Hospital Ambulatory Medical
      Care Survey-Ambulatory Surgery 2010 were abstracted for cases with a diagnosis of
      OM and myringotomy and tube (MT) procedures in children, respectively. Sex, race,
      ethnic, and insurance distributions were computed for OM and MT and then compared
      for healthcare disparities between rates of OM diagnoses and MT procedures.
      RESULTS: A total of 13.6 million ambulatory pediatric OM diagnoses were
      identified in 2010 (55.9% male; 82.4% white, 11.3% black, and 6.3% other; 14.3%
      Hispanic, 85.7% non-Hispanic). A total of 413 thousand ambulatory myringotomy
      procedures were identified (59.6% male; 86.0% white, 11.0% black, and 3.0% other;
      13.0% Hispanic, 87.0% non-Hispanic). There was no statistically significant
      difference in the provision of MT versus OM diagnosis according to sex (P =
      0.400), race (P = 0.313), or ethnicity (P = 0.228). There was also no
      statistically significant difference in the percentage of Medicaid coverage for
      OM children (37.0%) versus those undergoing MT (31.1%; P = 0.376). There does,
      however, appear to be a statistically higher percentage of non-Hispanic children
      being diagnosed with otitis media than Hispanic children (P = 0.049). CONCLUSION:
      There were no significant demographic differences in the incidence of children
      with OM undergoing MT with respect to sex, race, ethnicity, or insurance status.
      As a specialty, otolaryngology does not appear to exhibit any disparate
      healthcare access bias in providing MT to children with OM. LEVEL OF EVIDENCE:
      NA. Laryngoscope, 2018.

PMID- 30229911
TI  - Transport of ACE Inhibitory Peptides Ile-Gln-Pro and Val-Glu-Pro Derived from
      Spirulina platensis Across Caco-2 Monolayers.
AB  - : This study evaluated transepithelial transport mechanisms of Ile-Gln-Pro (IQP)
      and Val-Glu-Pro (VEP), two ACE-inhibitory peptides derived from Spirulina
      platensis, using human intestinal Caco-2 cell monolayers. IQP and VEP were
      absorbed intact through Caco-2 cell monolayers with Papp values of 7.48 +/- 0.58
      * 10-6 and 5.05 +/- 0.74 * 10-6 cm/s, respectively. The transport of IQP and VEP
      were affected neither by Gly-Pro nor by wortmannin, indicating that they were not
      PepT1-mediated and did not involve endocytosis. However, transport of IQP and VEP
      were increased significantly by sodium deoxycholate, suggesting that the major
      transport mechanism was paracellular. In addition, the increased transport of VEP
      and IQP were followed with the addition of sodium azide, suggesting influence of
      energy to the process. The transport of VEP was also increased by verapamil,
      indicating an apical-to-basolateral flux mediated by P-gp. PRACTICAL APPLICATION:
      Bioactive peptides derived from food proteins have been considered as potentially
      ideal products to reduce hypertension because of their safety and positive
      impacts on health. IQP and VEP are the 2 ACE inhibitory peptides derived from
      Spirulina platensis, a kind of edible cyanobacteria with rich nutrition and
      multiple physiological functions, and were demonstrated to inhibit ACE and lower
      blood pressure in spontaneously hypertensive rats. However, it is prerequisite
      that such bioactive peptides must be absorbed intact across the intestinal
      epithelium, so as to exert antihypertensive effects in vivo. This study evaluated
      transepithelial transport mechanisms of IQP and VEP. It contributes to the study
      of Spirulina in lowering blood pressure and supports the development of bioactive
      peptide products.

PMID- 30229913
TI  - Association of the genetic polymorphisms in immunoinflammatory microRNAs with
      risk of ischemic stroke and subtypes in an Iranian population.
AB  - Stroke is one of the most common type of cerebrovascular disease threatening
      human health and life with high mortality, disability, and morbidity. Ischemic
      stroke (IS) is determined to be a complex disease containing a group of
      heterogeneous disorders with various environmental and genetic risk factors. This
      study evaluated the polymorphisms of microRNAs involved in inflammatory routes
      leading to stroke in an Iranian population. This study evaluated the associations
      of hsa-mir-608 C/G rs4919510, hsa-mir-499 A/G rs3746444, and hsa-mir-145 C/T
      rs190323149 polymorphisms in precursor miRNAs with the risk of IS. These microRNA
      polymorphisms were analyzed in 470 patients with IS and 489 control subjects. The
      TOAST criteria was applied for IS subtypes classification. The frequency of the
      allele G of hsa-mir-499/rs3746444 A/G revealed significant association with IS in
      comparison with controls ( p < 0.0001, OR = 1.838, 95% CI = 1.406-2.401).
      Increased IS risks were associated with hsa-mir-499/ rs3746444 A/G genotypes in
      diverse genetic model (homozygote comparison: p = 0.004, OR = 2.136, 95% CI =
      1.269-3.597; heterozygote comparison: p = 0.029, OR = 1.373, 95% CI = 1.033
      1.825). Statistical analysis in IS subtypes showed that cardio-embolic patients
      compared with other subtypes (large artery atherosclerosis and lacunar) had
      higher frequency of G allele (LAA vs. CEI, p = 0.017; LAC vs. CEI, p = 0.009), AG
      genotype (LAA vs. CEI, p = 0.016; LAC vs. CEI, p = 0.013). Nevertheless, this
      study did not find any association between the alleles and genotypes of mir-608
      C/G rs4919510 SNP and IS, respectively ( p > 0.05). The current investigation
      provided verification that hsa-mir-499 rs3746444 A/G polymorphism may be
      associated with a significantly increased risk of IS in an Iranian population.

PMID- 30229914
TI  - In reference to accuracy and reliability of the flow coupler in postoperative
      monitoring of head and neck free flaps.

PMID- 30229915
TI  - Early 2D/3D ultrasound diagnosis of pleural effusion in fetuses with Turner
      syndrome.
AB  - Most guidelines on ultrasound examinations during pregnancy do not recommend
      routine early pregnancy scan in uncomplicated and asymptomatic pregnancies (ie,
      before 10 weeks based on last menstrual period). There is, however, a growing
      patient's expectation to have an early scan to confirm dating and verify the
      pregnancy is intrauterine and viable. We present three well-documented cases of
      patients who had an early (7-8 weeks) dating transvaginal scan revealing pleural
      effusion in the embryo. In all cases cytogenetic analysis confirmed monosomy for
      the X chromosome, consistent with a clinical diagnosis of Turner syndrome.

PMID- 30229916
TI  - In Response to In Reference to Intervention for Elevated Intracranial Pressure
      Improves Success Rate After Repair of Spontaneous Cerebrospinal Fluid Leaks.

PMID- 30229917
TI  - The predictive value of intra-left atrial mechanical delay for 1-year recurrence
      of atrial fibrillation after catheter ablation: A clinical follow-up study using
      dual Doppler echocardiography.
AB  - PURPOSE: The availability of dual Doppler echocardiography (DDE), which
      facilitates the simultaneous recording of Doppler waveforms at two different
      sites, has enhanced ability to assess single-beat atrial mechanical delay. We
      sought to investigate the predictive value of intra-left atrial mechanical delay
      for atrial fibrillation (AF) recurrence after radiofrequency catheter ablation
      (RFCA) with DDE. METHODS: Eighty-six patients with paroxysmal AF scheduled to
      undergo RFCA were prospectively enrolled. Intra-atrial and interatrial mechanical
      delays were evaluated by DDE and traditional tissue Doppler imaging (tTDI),
      respectively. The time of whole analysis process with each method was recorded.
      After RFCA, patients were followed for 1 year. RESULTS: Thirty (34.88%) patients
      had AF recurrence, and 56 (65.12%) patients maintained sinus rhythm. Cut-off
      values of 39.38 ms for intra-left atrial mechanical delay obtained by DDE and
      32.70 ms by tTDI predicted AF recurrence. Areas under curves were comparable in
      receiver operator characteristic analysis (P > .05). The whole analysis time of
      DDE was less than tTDI. Parameters obtained by DDE had better reproducibility.
      CONCLUSION: Intra-left atrial mechanical delay best predicted 1-year AF
      recurrence after RFCA. Compared with tTDI, DDE can noninvasively assess single
      beat atrial mechanical delay with high predictive power, less analysis time, and
      better reproducibility.

PMID- 30229918
TI  - Long-term outcomes of cartilage-buttressed T-tube tympanoplasty for prolonged
      middle ear ventilation.
AB  - OBJECTIVES/HYPOTHESIS: To report on the safety and efficacy of cartilage
      buttressed T-tube tympanoplasty for long-term middle ear ventilation,
      specifically by examining duration of tube survival, as well as adverse events
      associated with prolonged middle ear intubation, including persistent tympanic
      membrane perforation. STUDY DESIGN: Retrospective case series of patients
      undergoing cartilage-buttressed T-tube tympanoplasty between January 2005 and
      December 2016 in a tertiary-care neurotology private practice. METHODS: Patients
      who underwent cartilage T-tube tympanoplasty with complete pre- and postoperative
      audiometric data and a minimum follow-up duration of 12 months were analyzed. T
      tube survival and adverse events including persistent tympanic membrane
      perforation were recorded and compared to published data for other long-term
      middle ear ventilation techniques. RESULTS: The study cohort included 72
      cartilage-buttressed T-tube tympanoplasties in 68 patients. Median tube survival
      was 34 months (range, 2-131 months). Incidence of persistent tympanic membrane
      perforation (n = 1) was 1.4% CONCLUSIONS: Cartilage-buttressed T-tube
      tympanoplasty is a safe and effective means of accomplishing long-term middle ear
      ventilation with a considerably lower rate of persistent tympanic membrane
      perforation as compared to alternative methods of prolonged middle ear
      ventilation. LEVEL OF EVIDENCE: 4 Laryngoscope, 2017.

PMID- 30229919
TI  - Membranous subaortic stenosis coexisting with hypertrophic cardiomyopathy: A case
      report.
AB  - Subaortic stenosis (SAS) is a congenital heart disease, and its association with
      hypertrophic cardiomyopathy is very rare and clinically underappreciated. We
      report here a case of a 45-year-old female who was admitted to our hospital with
      chest tightness and shortness of breath. Both transthoracic and transesophageal
      echocardiography revealed asymmetric left ventricular hypertrophy and a membrane
      like echo below the level of the aortic valve. This patient was diagnosed with
      membranous SAS with hypertrophic cardiomyopathy. Screening of her immediate
      family members revealed that her son also had hypertrophic cardiomyopathy. The
      patient chose conservative treatments and has been closely followed-up after
      discharge.

PMID- 30229920
TI  - Fabrication and characterization of 3D-printed elastic auricular scaffolds: A
      pilot study.
AB  - OBJECTIVE: Aesthetic reconstruction of the external ear is challenging due to the
      complex anatomical shape of the auricle. Recently, artificial scaffolds such as
      Medpor (Stryker, Kalamasoo, MI, USA) have become widely used in ear
      reconstruction. However, the Medpor scaffold is stiffer than the natural ear,
      which may lead to discomfort, and moreover has uniform design for every patient.
      In this study, we investigated whether three-dimensional (3D)-printed artificial
      polyurethane (PU) scaffolds are suitable for auricular reconstruction. METHODS:
      PU scaffolds were fabricated using 3D printing according to a design derived from
      a digital imaging and communications in medicine (DICOM) image of the human
      auricle. The microstructure of the scaffolds was observed using scanning electron
      microscopy, and the porosity was examined. Cell proliferation on the scaffolds
      was assessed in vitro using tonsil-derived mesenchymal stem cells to evaluate the
      biocompatibility of the scaffolds. The scaffolds were implanted in C57BL/6 mice,
      and histological analysis was performed. RESULTS: The structural study revealed
      that the 3D-printed porous PU scaffolds have rectangular microstructure with
      regular pitch and line, as well as high porosity (56.46% +/- 10.22%) with a pore
      diameter of 200 um. The mechanical properties of the 3D-printed PU scaffolds were
      similar to those of the human auricle cartilage. Cell proliferation on the PU
      scaffolds was greater than that on Medpor scaffolds. Histological evaluation
      demonstrated that the porous parts of the PU scaffolds became filled with
      collagen and vascular tissue. CONCLUSION: Elastic, porous PU scaffolds can be
      obtained using 3D printing, have biomechanical properties similar to those of the
      natural ear, and are suitable for use in auricular reconstruction. LEVEL OF
      EVIDENCE: NA. Laryngoscope, 2018.

PMID- 30229921
TI  - Prevalence and resource utilization for vocal fold paralysis/paresis after
      esophagectomy.
AB  - OBJECTIVES/HYPOTHESIS: Vocal fold paralysis/paresis (VFP) is an uncommon but
      serious complication following esophagectomy. The objectives of this study were
      to: 1) identify the prevalence of VFP and associated complications after
      esophagectomy in the United States, and 2) determine the utilization and
      otolaryngology-head and neck surgery/speech-language pathology (OHNS/SLP) and
      predictors of such utilization in the management of these patients. STUDY DESIGN:
      Retrospective database analysis. METHODS: The National Inpatient Sample (NIS)
      represents a 20% stratified sample of discharges from US hospitals. Using
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes, patients undergoing esophagectomy between 2008 and 2013 were identified in
      the NIS. Subcohorts of patients with VFP and OHNS/SLP utilization were also
      identified. Weighted logistic regression models were used to compare binary
      outcomes such as complications; generalized linear models were used to compare
      total hospital charges and length of stay (LOS). RESULTS: We studied 10,896
      discharges, representing a weighted estimate of 52,610 patients undergoing
      esophagectomy. The incidence of VFP after esophagectomy was 1.96%. Compared to
      those without VFP, patients with VFP had a higher incidence of postoperative
      pneumonia, more medical complications, and were more likely to undergo
      tracheostomy; hospital charges and LOS were also higher. Of the patients with
      VFP, 35.0% received OHNS/SLP intervention. CONCLUSIONS: VFP after esophagectomy
      is associated with postoperative complications, prolonged LOS, and higher
      hospital costs. OHNS/SLP intervention occurred in roughly one-third of
      postesophagectomy VFP patients, suggesting there may be opportunities for
      enhanced evaluation and management of these patients. LEVEL OF EVIDENCE: 4
      Laryngoscope, 2018.

PMID- 30229922
TI  - Voice Outcome Measures for Adult Patients With Unilateral Vocal Fold Paralysis: A
      Systematic Review.
AB  - OBJECTIVES: Unilateral vocal fold paralysis (UVFP) typically results in marked
      changes in voice quality and performance and has a significant impact on quality
      of life. Treatment approaches generally aim to restore glottal closure for
      phonation and improve vocal function. There are a wide range of voice outcome
      measures that are available to measure the treatment effect. Careful selection of
      voice outcome measures is required to ensure that they are adequate for purpose
      and are psychometrically sound to detect the treatment effect. This article aims
      to critically evaluate the literature for voice outcome measures that are used
      for patients with UVFP. STUDY DESIGN: Systematic review. METHODS: Nine databases
      were searched for UVFP treatment studies published since 2003 (n = 2,484
      articles). These articles and their references were screened using
      inclusion/exclusion criteria, including population characteristics, treatment,
      voice outcomes, and study findings. Data from the included articles was extracted
      and appraised with respect to multidimensionality, timing, selection rationale,
      validity, reliability, and responsiveness to change of the voice outcome
      measures. RESULTS: A total of 29 studies met the inclusion criteria for the
      systematic review. These studies showed considerable variability in the
      rationale, selection, and application of voice outcome measures for reporting the
      treatment effect for patients with UVFP. CONCLUSION: There is currently a
      significant disparity in the selection and use of voice outcome measures for
      patients with UVFP. A set of principles around selection rationale, validity,
      reliability, and responsiveness to change is proposed to enhance the judicious
      selection of voice outcome measures for this patient group. Laryngoscope, 2018.

PMID- 30229923
TI  - Patient-reported olfaction improves following outside-in Draf III frontal sinus
      surgery for chronic rhinosinusitis.
AB  - OBJECTIVES: The Draf III frontal sinusotomy is an established surgical procedure
      with an important role in the surgical management of recalcitrant chronic
      rhinosinusitis (CRS). In 2012, the outside-in approach to the Draf III was
      described as a safe and efficient procedure. Smell recovery in inflammatory CRS
      is challenging, and to date there is limited evidence suggesting that Draf III
      improves patient-reported olfactory dysfunction from CRS. METHODS: A consecutive
      series of patients who underwent an outside-in Draf III for inflammatory CRS by a
      single, tertiary rhinologist were reviewed. Patients were excluded if the Draf
      III was performed for noninflammatory conditions. Postoperatively, patients were
      maintained on long-term corticosteroid irrigations, and adherence was assessed.
      Prospectively collected data included patient demographics, a visual analogue
      scale for smell, overall Sinonasal Outcome Test Score (SNOT-22), global nasal
      function score, and a clinician-graded clinical outcome score. RESULTS: One
      hundred and four patients (41.1% female) aged 54 +/- 12 years underwent an
      outside-in Draf III. The median follow-up time was 30.6 months (range 12.2-72.1).
      The majority of patients rated their smell loss as moderate or worse
      preoperatively; however, this was significantly improved at postoperative review
      (71.2% vs. 27.6%; Kendall tau-b, P < 0.01). The SNOT-22 score improved after
      surgery (2.32 +/- 1.09 vs. 0.78 +/- 0.69, P < 0.0001). Medication adherence was
      significantly associated with improved clinical outcome score (Kendall tau-b, P <
      0.004). Aspirin exacerbated respiratory disease was found to be a significant
      risk factor predicting poor clinical outcome on univariate analysis (Odds Ratio =
      4.69 (1.03-21.2), P = 0.04). CONCLUSION: The outside-in Draf III appears to
      facilitate sustained, meaningful improvement in several self-reported outcomes,
      including smell. However, further study and comparison to less aggressive surgery
      will be required to confirm its true benefit. LEVEL OF EVIDENCE: Level 4.
      Laryngoscope, 2018.

PMID- 30229924
TI  - Intranasal Corticosteroids Do Not Lead to Ocular Changes: A Systematic Review and
      Meta-analysis.
AB  - OBJECTIVES: The safety and efficacy of intranasal corticosteroids (INCS) are well
      established, but there remains apprehension that INCS could lead to systemic side
      effects, as with oral steroids. The objective of this systematic review was to
      assess whether the use of INCS lead to increased intraocular pressure (IOP) above
      20 mm Hg, glaucoma, or formation of posterior subcapsular cataracts in adult
      patients with rhinitis. METHODS: Two medical librarians searched the published
      literature for records discussing the use of "nasal steroids" in "rhinitis" and
      their effect on "intraocular pressure," "cataracts," or "glaucoma." RESULTS: A
      total of 484 studies were identified, and 10 randomized controlled trials met our
      inclusion criteria. Meta-analysis of 2,226 patients revealed that the relative
      risk of elevated IOP in those who received INCS was 2.24 (95% confidence interval
      [CI]: 0.68 to 7.34) compared to placebo. The absolute increased incidence of
      elevated IOP in patients using INCS compared to placebo was 0.8% (95% CI: 0% to
      1.6%). There were zero cases of glaucoma in both placebo and INCS groups at 12
      months. The absolute increased incidence of developing a posterior subcapsular
      cataract was 0.02% (95% CI: -0.3% to 0.4%). CONCLUSIONS: Use of INCS is not
      associated with a significant risk of elevating IOP or developing a posterior
      subcapsular cataract in patients with allergic rhinitis. Presence of glaucoma,
      however, is the real clinical adverse event of concern. There were zero reported
      cases of glaucoma at 12 months. Future studies should formally evaluate for
      glaucoma rather than use IOP measures as a surrogate. Laryngoscope, 2018.

PMID- 30229925
TI  - Generation of procoagulant collagen- and thrombin-activated platelets in platelet
      concentrates derived from buffy coat: the role of processing, pathogen
      inactivation, and storage.
AB  - BACKGROUND: Collagen- and thrombin-activated (COAT) platelets (PLTs), generated
      by dual-agonist stimulation with collagen and thrombin (THR), enhance THR
      generation at the site of vessel wall injury. There is evidence that higher
      amounts of procoagulant COAT PLTs are associated with stroke, while a decreased
      ability to generate them is associated with bleeding diathesis. Our aim was to
      study PLT functions, particularly the ability to generate COAT PLTs, in PLT
      concentrates (PCs) from buffy coat. Thus, we investigated the effect of
      processing, pathogen inactivation treatment (amotosalen-UVA), and PC storage.
      STUDY DESIGN AND METHODS: Two PCs from five donors each were pooled and split in
      two bags; one of them was pathogen inactivated and the other one was left
      untreated (n = 5). Flow cytometric analyses were performed immediately after PC
      preparation (Day 1) and thereafter on Days 2, 5, 7, and 9 in treated and
      untreated PCs to measure the reactivity of PLTs (CD62P and PAC-1), the content
      and secretion of dense granule after stimulation with different agonists, and the
      percentage of COAT PLTs after dual stimulation with convulxin (agonist of the
      collagen receptor GPVI) and THR. RESULTS: Preparation of PCs resulted in a
      significant decrease of COAT PLTs and in an impaired response to adenosine 5'
      diphosphate sodium (ADP). Storage further decreased ADP response. Minor
      differences were observed between untreated or amotosalen-UVA-treated PCs.
      CONCLUSION: Preparation of PCs from buffy coats decreased the ability to generate
      COAT PLTs and impaired PLT response to ADP.

PMID- 30229926
TI  - Population Pharmacokinetics and Exposure-Response Relationship of Intravenous and
      Subcutaneous Abatacept in Patients With Rheumatoid Arthritis.
AB  - Abatacept population pharmacokinetics (PK) and exposure-response (E-R) models for
      selective efficacy end points were developed using phase 2 and 3 study data in
      patients with rheumatoid arthritis treated with abatacept (intravenous [IV] or
      subcutaneous [SC]), followed by simulations. Two efficacy end points were
      assessed in the E-R analyses: Disease Activity Score in 28 joints (DAS28) and
      American College of Rheumatology response criteria for 20/50/70% improvement
      (ACR20/50/70). The analyses were performed with data from 11 clinical studies for
      the population PK analysis and from 3 clinical studies for the E-R analyses
      (DAS28 and ACR20/50/70). The PK of abatacept were time invariant and can be
      described by a linear 2-compartment model with first-order elimination and with
      zero-order IV infusion or first-order absorption for SC abatacept. Baseline body
      weight was the only clinically meaningful covariate; that is, abatacept clearance
      and volume of central compartment increased with increasing baseline body weight.
      Steady-state trough concentration (Cminss ) of abatacept was identified as the
      best exposure predictor of DAS28 response compared with other exposure measures.
      In addition, the E-R relationship was the same for IV and SC abatacept. Similar
      results were confirmed in the ACR20/50/70 E-R analyses. Efficacy responses
      increased with increasing Cminss and a near-maximal response was associated with
      Cminss >=10 MUg/mL. The model-based analyses confirmed that the weight-tiered ~10
      mg/kg IV and fixed 125 mg SC abatacept dosing regimens are comparable and
      achieved plateau responses, by delivering Cminss >=10 MUg/mL in RA patients
      across all body weights.

PMID- 30229927
TI  - Short-term effects of levosimendan on strain/strain rate markers in patients with
      nonischemic dilated cardiomyopathy.
AB  - OBJECTIVE: To investigate whether repetitive measurements of speckle tracking
      echocardiography (STE)-derived strain (S) and strain rate (SR) could reveal
      changes in left ventricular function in patients with nonischemic dilated
      cardiomyopathy treated with levosimendan. METHODS: We included 22 consecutive
      patients (age 53 +/-12 years) with an ejection fraction (EF) below 35% and New
      York Heart Association (NYHA) class III-IV symptoms that required intravenous
      inotropic support despite optimal medical therapy. The absence of any occlusive
      coronary artery disease was identified via previous coronary angiography in all
      patients. Echocardiographic variables, including strain/strain rate, and NYHA
      functional class, were evaluated before and after levosimendan infusion at the
      72nd hour and one month. RESULTS: The strain and strain rate values for both left
      and right ventricles were observed to be increased NYHA functional class and left
      ventricular EF (P <.05). CONCLUSION: STE can successfully completed conventional
      echocardiography in the evaluation of patients with decompensated heart failure
      who were treated with levosimendan.

PMID- 30229928
TI  - Social and community program approaches to participants: Exploring best
      practices.
AB  - This article presents the results of a deepened study of the best practices and
      outcomes of 15 programs (across 9 countries) that work with socioeconomically
      disadvantagedd communities. Using thematic analysis, we identified best practices
      that participants, community leaders, and professionals recognized as key. Data
      collection involved in loco observation and semistructured interviews with
      participants and professionals, and focus groups with professionals. Associated
      with best practices, programs adopted two central perspectives on approaching
      participants: approaching participants as users and approaching participants as
      contributors. Such approaches were crossed with best practices and outcomes
      identified througout the analysis. For programs that approached participants as
      users, the best practices were valuing, facilitating the access to resources,
      showing availability, and promoting competencies and openness, and the main
      outcome was participants' improved self-confidence. For programs that approached
      participants as contributors, the best practices were contributing, encouraging
      participation, valuing participants, becoming masters, and reciprocity, and the
      main outcome was participants having an impact.

PMID- 30229929
TI  - First trimester expression of anorectal malformation: Case report and review of
      the literature.
AB  - A 26-years-old woman, underwent an ultrasound examination at 13.4 weeks. A cystic
      structure was identified in the right lower abdomen. Gradually, the cystic mass
      was replaced by echogenic content and eventually attained the appearance of
      hyperechoic bowel. At 21.2 weeks, the anal sphincter could not be demonstrated
      which was consistent with the diagnosis of isolated anal agenesis. Amniocentesis
      revealed 46XY karyotype with normal comparative genomic hybridization. After
      termination of pregnancy at 23 weeks, an autopsy revealed an isolated high type
      anorectal malformation (ARM) without fistula. We reviewed all 14 cases reported
      in the literature of first trimester sonographic expression of ARM.

PMID- 30229930
TI  - Reproducibility of the lung anatomy under active breathing coordinator control:
      Dosimetric consequences for scanned proton treatments.
AB  - PURPOSE: The treatment of moving targets with scanned proton beams is
      challenging. For motion mitigation, an Active Breathing Coordinator (ABC) can be
      used to assist breath-holding. The delivery of pencil beam scanning fields often
      exceeds feasible breath-hold durations, requiring high breath-hold
      reproducibility. We evaluated the robustness of scanned proton therapy against
      anatomical uncertainties when treating nonsmall-cell lung cancer (NSCLC) patients
      during ABC controlled breath-hold. METHODS: Four subsequent MRIs of five healthy
      volunteers (3 male, 2 female, age: 25-58, BMI: 19-29) were acquired under ABC
      controlled breath-hold during two simulated treatment fractions, providing both
      intrafractional and interfractional information about breath-hold
      reproducibility. Deformation vector fields between these MRIs were used to deform
      CTs of five NSCLC patients. Per patient, four or five cases with different tumor
      locations were modeled, simulating a total of 23 NSCLC patients. Robustly
      optimized (3 and 5 mm setup uncertainty respectively and 3% density perturbation)
      intensity-modulated proton plans (IMPT) were created and split into subplans of
      20 s duration (assumed breath-hold duration). A fully fractionated treatment was
      recalculated on the deformed CTs. For each treatment fraction the deformed CTs
      representing multiple breath-hold geometries were alternated to simulate repeated
      ABC breath-holding during irradiation. Also a worst-case scenario was simulated
      by recalculating the complete treatment plan on the deformed CT scan showing the
      largest deviation with the first deformed CT scan, introducing a systematic
      error. Both the fractionated breath-hold scenario and worst-case scenario were
      dosimetrically evaluated. RESULTS: Looking at the deformation vector fields
      between the MRIs of the volunteers, up to 8 mm median intra- and interfraction
      displacements (without outliers) were found for all lung segments. The dosimetric
      evaluation showed a median difference in D98% between the planned and breath-hold
      scenarios of -0.1 Gy (range: -4.1 Gy to 2.0 Gy). D98% target coverage was more
      than 57.0 Gy for 22/23 cases. The D1 cc of the CTV increased for 21/23
      simulations, with a median difference of 0.9 Gy (range: -0.3 to 4.6 Gy). For
      14/23 simulations the increment was beyond the allowed maximum dose of 63.0 Gy,
      though remained under 66.0 Gy (110% of the prescribed dose of 60.0 Gy). Organs at
      risk doses differed little compared to the planned doses (difference in mean
      doses <0.9 Gy for the heart and lungs, <1.4% difference in V35 [%] and V20 [%] to
      the esophagus and lung). CONCLUSIONS: When treating under ABC controlled breath
      hold, robustly optimized IMPT plans show limited dosimetric consequences due to
      anatomical variations between repeated ABC breath-holds for most cases. Thus, the
      combination of robustly optimized IMPT plans and the delivery under ABC
      controlled breath-hold presents a safe approach for PBS lung treatments.

PMID- 30229931
TI  - Readmission after surgery for oropharyngeal cancer: An analysis of rates, causes,
      and risk factors.
AB  - OBJECTIVES/HYPOTHESIS: Determine the rate, diagnoses, and risk factors associated
      with 30-day nonelective readmissions for patients undergoing surgery for
      oropharyngeal cancer. STUDY DESIGN: Retrospective cohort study. METHODS: We
      analyzed the Nationwide Readmissions Database for patients who underwent
      oropharyngeal cancer surgery between 2010 and 2014. Rates and causes of 30-day
      readmissions were determined. Multivariate logistic regression was used to
      identify risk factors for readmission. RESULTS: Among 16,902 identified cases,
      the 30-day, nonelective readmission rate was 10.2%, with an average cost per
      readmission of $14,170. The most common readmission diagnoses were postoperative
      bleeding (14.1%) and wound complications (12.6%) (surgical site infection [8.6%],
      dehiscence [2.3%], and fistula [1.7%]). On multivariate regression, significant
      risk factors for readmission were major ablative surgery (which included total
      glossectomy, pharyngectomy, and mandibulectomy) (odds ratio [OR]: 1.29, 95%
      confidence interval [CI]: 1.06-1.60), advanced Charlson/Deyo comorbidity (OR:
      2.00, 95% CI: 1.43-2.79), history of radiation (OR: 1.58, 95% CI: 1.15-2.17),
      Medicare (OR: 1.34, 95% CI: 1.06-1.69) or Medicaid (OR: 1.82, 95% CI: 1.32-2.50)
      payer status, index admission from the emergency department (OR: 1.19, 95% CI:
      1.02-1.40), and length of stay >=6 days (OR: 1.57, 95% CI: 1.19-2.08).
      CONCLUSIONS: In this large database analysis, we found that approximately one in
      10 patients undergoing surgery for oropharyngeal cancer is readmitted within 30
      days. Procedural complexity, insurance status, and advanced comorbidity are
      independent risk factors, whereas postoperative bleeding and wound complications
      are the most common reasons for readmission. LEVEL OF EVIDENCE: 4. Laryngoscope,
      2018.

PMID- 30229932
TI  - Determination of Iodine Value in Hydrogenated Oils: Comparison of Titration and
      Gas Chromatography with Flame-Ionization Detection Methodologies.
AB  - The United States Food and Drug Administration (FDA) recently issued its final
      determination that partially hydrogenated oils (PHO) are no longer generally
      recognized as safe (GRAS) for any use in human food. Consequently, the
      discrimination between PHO and fully hydrogenated oils (FHO), which is achieved
      by the iodine value (IV), has become an important regulatory issue. This study
      compared American Oil Chemists' Society (AOCS) and International Organization for
      Standardization (ISO) titration and gas chromatography with flame-ionization
      detection (GC-FID) methodologies for the determination of IV in seven samples of
      hydrogenated oil, namely coconut, cottonseed (n = 2), palm kernel, palm stearine,
      and soybean (n = 2) oils. Titrations produced statistically higher IV
      determinations than those achieved by GC-FID, for all samples except the FH
      coconut oil. The unsaponifiable matter content of the hydrogenated oils, which
      varied from 0.15% to 0.47% of total fat, likely contributed modest increases to
      the IV by titration. Both methodologies were prone to issues at low IV (~4), with
      titrations showing greater variability, and GC-FID being susceptible to
      incomplete separation, identification, and quantification of all unsaturated
      fatty acids. The variability observed with titrations could be minimized by
      careful execution of the titration protocol. Although both approaches
      successfully discriminated PHO and FHO in the test materials, at low IV (~4),
      titration is the most accurate method for determining the IV, and the only
      approach that has been validated in oils with a very low IV (<1).

PMID- 30229933
TI  - Diagnosis of vocal cord leukoplakia: The role of a novel narrow band imaging
      endoscopic classification.
AB  - OBJECTIVES: The purpose of this study was to introduce a new narrow band imaging
      (NBI) endoscopic classification for the diagnosis of vocal cord leukoplakia.
      STUDY DESIGN: Case series. METHODS: From January 2010 to February 2018, a total
      of 120 cases of vocal cord leukoplakia were enrolled in this study. The NBI
      endoscopic system was used to examine the vocal cords. Each lesion was observed
      by NBI endoscopy and evaluated according to the detailed morphologic findings of
      intraepithelial papillary capillary loop (IPCL). The superficial IPCL patterns
      were classified into six types (types I-VI). The differential diagnosis abilities
      of NBI classification for benign and malignant leukoplakia were investigated.
      RESULTS: Out of the 120 cases of vocal cord leukoplakia, 81% (97 of 120) related
      to benign lesions (including inflammation, epithelial proliferation,
      hyperkeratosis, dyskeratosis, mild dysplasia, and moderate dysplasia); the
      remaining 19% (23 of 120) consisted of malignant lesions (including severe
      dysplasia, carcinoma in situ, and invasive carcinoma). The accuracy of
      differential diagnosis for vocal cord leukoplakia using NBI endoscopy was up to
      90.8% (109 of 120), significantly higher than that of white light imaging (70.0%,
      84 of 120) (chi2  = 16.536, P =  0.000). The sensitivity, specificity, and
      positive and negative predictive values of the diagnosis for malignant vocal cord
      leukoplakia under the NBI endoscope were 82.6%, 92.8%, 73.1%, and 95.7%,
      respectively. There is relatively good consistency between the NBI endoscopic
      diagnosis and pathological diagnosis (kappa = 0.718, P = 0.000). CONCLUSION: The
      new NBI endoscopic classification of vocal cord leukoplakia can improve the
      accuracy of distinguishing benign and malignant leukoplakia. LEVEL OF EVIDENCE:
      4. Laryngoscope, 2018.

PMID- 30229934
TI  - Technical Note: Virtual CT for reducing CT dose in targeted radionuclide therapy
      dosimetry.
AB  - PURPOSE: Previously we have shown that using sequential CT images is superior to
      sequential SPECT for nonrigid registration in three-dimensional (3D) targeted
      radionuclide therapy (TRT) dosimetry. However, sequential CTs are often not
      available due to radiation concerns. In this paper, we propose a virtual CT (vCT)
      method for attenuation and scatter correction, image registration, and
      segmentation for improved dosimetric accuracy with single CT acquisition.
      METHODS: We used a population of nine XCAT phantoms with different In-111 Zevalin
      biokinetics and anatomical variations for the simulations. An analytical
      projector was used to simulate sequential SPECT/CT acquisitions for a medium
      energy general purpose collimator at 1, 12, 24, 72, and 144 h postinjection,
      modeling attenuation, scatter, and geometric collimator-detector response. The
      corresponding sequential attenuation maps of the phantoms served as real CT (rCT)
      images. For vCT generation, we investigated three registration methods, that is,
      (a) SPECT to SPECT; (b) SPECT to CT, and (c) CT to SPECT, and the optimal time
      point for single CT acquisition. Difference images and average normalized mean
      square errors (NMSE) were calculated between different vCTs and their
      corresponding rCTs. Absorbed dose and dose-volume histograms (DVHs) for critical
      organs were computed for the rCT, optimized vCT, and conventional single CT (1CT)
      protocols, respectively, for dosimetric analyses. RESULTS: For vCT generation,
      SPECT to SPECT registration with a single CT acquired at the first time point
      shows the smallest difference and NMSE. For organ absorbed doses, the results of
      vCT were similar to those of rCT and were superior to 1CT, that is, -0.24 +/-
      1.56% vs -0.49 +/- 1.76% vs -6.37 +/- 5.63% for the liver, -1.05 +/- 2.89% vs 
      0.69 +/- 2.74% vs -4.87 +/- 4.35% for kidneys, respectively. The results of DVHs
      also showed improvement for all organs using vCTs as compared to the conventional
      1CT protocol. CONCLUSION: The optimized vCT method can effectively increase the
      TRT dosimetric results if there is only a single CT available in the sequential
      imaging protocol, reducing the substantial increase in radiation burden from
      repeated CT scans.

PMID- 30229935
TI  - Dynamic Block Matching to assess the longitudinal component of the dense motion
      field of the carotid artery wall in B-mode ultrasound sequences - Association
      with coronary artery disease.
AB  - PURPOSE: The motion of the common carotid artery tissue layers along the vessel
      axis during the cardiac cycle, observed in ultrasound imaging, is associated with
      the presence of established cardiovascular risk factors. However, the vast
      majority of the (semi-)automatic methods devised to measure this so-called
      "longitudinal kinetics" phenomenon are based on the tracking of a single point,
      thus failing to capture the overall - and potentially inhomogeneous - motion of
      the entire arterial wall. The aim of this work is to introduce a motion tracking
      a framework to simultaneously extract the temporal trajectory of a large
      collection of points (several hundred) horizontally aligned and spanning the
      entire exploitable width of the image, thus providing a dense motion field.
      METHOD: The only action required from the user is to indicate the left and right
      borders of the region to be processed. A previously validated contour
      segmentation method is used to position one point in the arterial wall in each
      column of the image. Between two consecutive frames, the radial motion of each
      point is predetermined by the position of the segmentation contours. The
      longitudinal motion, which is the main focus of the present work, is determined
      in two steps. First, a series of independent block matching operations are
      carried out for all the tracked points. Here, the displacement of each point is
      not determined yet, instead the similarity map is stored. Then, an original
      dynamic-programming approach is exploited to regularize the collection of
      similarity maps and estimate the globally optimal motion over the entire vessel
      wall. Sixty-two atherosclerotic participants at high cardiovascular risk were
      involved in this study. Method training and validation was performed with 20 and
      42 participants, respectively. The amplitude-independent index sigmaX was
      introduced to quantitate the motion inhomogeneity across the length of the
      artery. RESULTS: A dense displacement field, describing the longitudinal motion
      of the carotid far wall over time, was extracted from all participants. For each
      cine-loop, the method was evaluated against manual reference tracings performed
      on three local points, and showed a good accuracy, with an average absolute error
      (+/- STD) of 150 (+/-163) MUm. It also demonstrated an overall greater robustness
      compared to a previously validated method based on single-point motion tracking.
      For all the 62 participants, the analyzed region had, in average, a width of 24.2
      mm, involving the simultaneous tracking of 357 points along 151 temporal frames,
      and requiring a total computational time of 68 s. Analyzing the inhomogeneity of
      the carotid artery motion showed a strong correlation between sigmaX and the
      presence of coronary artery disease (beta-coefficient = 0.586, P = 0.003).
      CONCLUSIONS: To the best of our knowledge, this is the first time that a method
      is specifically proposed to assess the dense motion field corresponding to the
      longitudinal kinetics of the carotid far wall. This approach has potential to
      evaluate the homogeneity (or lack thereof) of the wall dynamics. The proposed
      method has promising performances to improve the analysis of arterial
      longitudinal motion and the understanding of the underlying patho-physiological
      parameters.

PMID- 30229936
TI  - System justification: Experimental evidence, its contextual nature, and
      implications for social change.
AB  - We review conceptual and empirical contributions to system justification theory
      over the last fifteen years, emphasizing the importance of an experimental
      approach and consideration of context. First, we review the indirect evidence of
      the system justification motive via complimentary stereotyping. Second, we
      describe injunctification as direct evidence of a tendency to view the extant
      status quo (the way things are) as the way things should be. Third, we elaborate
      on system justification's contextual nature and the circumstances, such as
      threat, dependence, inescapability, and system confidence, which are likely to
      elicit defensive bolstering of the status quo and motivated ignorance of critical
      social issues. Fourth, we describe how system justification theory can increase
      our understanding of both resistance to and acceptance of social change, as a
      change moves from proposed, to imminent, to established. Finally, we discuss how
      threatened systems shore up their authority by co-opting legitimacy from other
      sources, such as governments that draw on religious concepts, and the role of
      institutional-level factors in perpetuating the status quo.

PMID- 30229937
TI  - Electronic medical record-based tools aid in timely triage of disc-shaped foreign
      body ingestions.
AB  - OBJECTIVES/HYPOTHESIS: Children presenting to the emergency department with coin
      shaped foreign body (FB) ingestion must be evaluated urgently to rule out a
      button battery. As many of these ingestions are well-appearing on presentation,
      delays in triage put patients at risk for further injury. STUDY DESIGN: Quality
      initiative. METHODS: A quality initiative, utilizing electronic medical record
      (EMR)-based tools, was implemented at our academic children's hospital. A chief
      complaint pertaining to coin-shaped FB ingestion was created and was linked to a
      best practice advisory, instructing assignment of acuity level 2 and the order of
      a Stat x-ray. A link to the hospital's relevant algorithm was provided. A review
      was conducted comparing children who underwent FB removal preinitiative (January
      1, 2016-January 28, 2017) and postinitiative (January 31, 2017-August 30, 2017).
      Primary outcomes were frequency of assignment of acuity level 2 and time from
      patient arrival to x-ray order placement and x-ray completion. RESULTS: Thirty
      six patients in the baseline group and 30 in the postintervention group underwent
      FB removal. The rate of appropriate acuity assignment increased from 63.8%
      (23/36) pre implementation to 100% (30/30) postimplementation (P = .0003). Median
      time from arrival to imaging ordered and completed decreased from 36.5 to 4
      minutes (95% confidence interval [CI]: -44 to -17) and 59 to 41 minutes (95% CI: 
      39 to -1), respectively. CONCLUSIONS: Utilization of EMR-based tools was
      associated with improved timeliness in initiation of care in metallic FB
      ingestion patients. Further initiatives will be aimed at downstream events in the
      diagnosis and treatment of these patients. LEVEL OF EVIDENCE: NA Laryngoscope,
      2018.

PMID- 30229938
TI  - Home transfusion: three decades of practice at a tertiary care hospital.
AB  - BACKGROUND: Hospital at Home (HH) provides specialized care at the patients'
      homes. Keeping patients in familial surroundings can result in better outcomes
      reducing readmission to hospital, mortality, and costs of care. Home transfusion
      (HT) can be a key element in HH management but is scarcely deployed due to
      concerns about safety and cost. We have reviewed our HT practice to assess its
      feasibility and safety. STUDY DESIGN AND METHODS: We prospectively reviewed data
      collected from 1985 to 2015, focusing specially on feasibility and procedural
      safety, looking for adverse events of transfusion. We also assessed the situation
      in similar hospitals in Spain with a survey about their practice. RESULTS: A
      total of 613 patients received 2260 blood components in 2126 transfusion
      episodes. A total of 93% patients received fewer than 10 transfusions. Most
      patients were treated for blood diseases (32%) or cancers (20%). The rate of
      adverse effects was 2.68% and decreased significantly with time. Fever was the
      most common adverse reaction. Patients who received transfusion of more than one
      blood product in a day were at higher risk of adverse events. No errors or near
      miss events were detected, and no patient had to be readmitted to hospital for
      this cause. The survey on HT practices in similar hospitals showed great
      variation in practice. CONCLUSION: HT is feasible, sustainable, and safe, when
      performed on selected patients by dedicated HH units with well-trained staff,
      under specific protocols.

PMID- 30229940
TI  - How Important Is a Closed-Loop Artificial Pancreas?

PMID- 30229939
TI  - A birch sublingual allergy immunotherapy tablet reduces rhinoconjunctivitis
      symptoms when exposed to birch and oak and induces IgG4 to allergens from all
      trees in the birch homologous group.
AB  - BACKGROUND: This randomized, double-blind trial was conducted to determine the
      optimal dose for clinical efficacy of the SQ tree SLIT-tablet. An environmental
      exposure chamber (EEC) was used to reduce variability of allergen exposure and
      allow investigation of symptom reduction towards different species from the birch
      homologous group in separate EEC sessions. METHODS: Eligible subjects (N = 219)
      were randomized to receive treatment with placebo or the SQ tree SLIT-tablet (2,
      7, or 12 DU) for 24 weeks. EEC pollen challenges were conducted outside the birch
      pollen season and included four birch and two oak EEC sessions. The primary
      efficacy endpoint was the average allergic rhinoconjunctivitis (ARC) total
      symptom score (TSS) after 24 weeks of treatment. RESULTS: There was a
      statistically significantly lower TSS during the 24-week birch EEC session for 7
      DU and 12 DU compared to placebo with relative differences of 24% (P = 0.03) and
      25% (P = 0.02). For the 24-week oak EEC session, there was a statistically
      significant difference for 12 DU (24%, P = 0.03). IgE and IgG4 measurements
      supported these findings and demonstrated cross-reactivity to all other species
      within the birch homologous group. Treatment was well-tolerated with the most
      frequently reported adverse reactions being the local reactions in the oral
      cavity of mild-to-moderate severity. CONCLUSION: This trial demonstrates that the
      SQ tree SLIT-tablet reduce ARC symptoms triggered by birch or oak pollen. The
      optimal dose for further development was 12 DU. Clinical and immunological
      findings suggest that the tablet may be used to treat allergies to all species
      within the birch homologous group.

PMID- 30229941
TI  - Hand-wrist, knee, and foot-ankle dosimetry and image quality measurements of a
      novel extremity imaging unit providing CBCT and 2D imaging options.
AB  - PURPOSE: Radiation dose is a general concern in diagnostic imaging and a special
      concern for children who are at greater risk from radiation effects. This study
      evaluates effective doses (E) produced during 2D and volume imaging with a novel
      cone beam computed tomography (CBCT) based extremity imaging device. The device's
      compact size and protocol options offer image choices that enhance the potential
      for reduced dose and improved diagnostics when evaluating sports injuries.
      METHODS: Hand-wrist, foot-ankle, and knee phantoms were developed for use with
      optically stimulated luminescent dosimeters (OSL). Dosimetry of transmission
      radiographs (2D) and CBCT volumes (3D) was assessed for Standard and lowered dose
      (Lite) exposure protocols. Effective dose was calculated for child and adult age
      groups. Image quality was assessed with contrast-to-noise ratio (CNR) and
      modulation transfer function (MTF). A figure of merit was calculated as the
      square of CNR divided by E. RESULTS: Standard 2D doses ranged from 0.001-0.06
      MUSv for adults, 0.001-0.05 MUSv for 15-yr olds, 0.003-0.13 MUSv for 10-yr olds,
      and 0.005-0.20 for 5-yr olds. Dose reductions with Lite protocols ranged from 26
      to 51%. Standard CBCT doses ranged from 0.3-4.6 MUSv for adults, 0.3-4.4 MUSv for
      15-yr olds, 0.6-9.8 MUSv for 10-yr olds, and 1-22.6 MUSv for 5-yr olds. For both
      2D and 3D a trend of increasing imaging dose with reduced age was present and was
      statistically significant for children below the age of 10 (P = 0.0009). Lite
      dose reductions averaged 47%. CNR was statistically reduced in Lite dose scans (P
      = 0.0384) but was not statistically different using FOM analysis (P = 0.3089).
      MTF was not significantly affected by the two dose protocols (P = 0.8104).
      CONCLUSION: CBCT effective doses calculated from anthropomorphic phantom
      exposures following manufacturer suggested protocols appear to be substantially
      less than previously reported doses for similar MDCT extremity examinations. In
      this study, effective dose from 2D radiographic imaging was approximately two
      orders of magnitude less than CBCT imaging. Doses were on the order of a few
      minutes to hours of ubiquitous per-capita background dose for 2D imaging and a
      few hours to days for 3D imaging. Dose significantly increased for children
      younger than age 10. Lite protocols resulted in substantial dose reductions and
      can be recommended for children and those examinations where reduced CNR will not
      affect diagnosis. Flexibility of 2D and 3D imaging options with low-dose
      protocols make this technology a promising option for radiographic evaluation of
      the extremities. Efficacy studies are needed to determine when MDCT, CBCT or
      Digital Radiography are best used for particular diagnostic tasks.

PMID- 30229942
TI  - Size-dependent Tumor Response to Photodynamic Therapy and Irinotecan
      Monotherapies Revealed by Longitudinal Ultrasound Monitoring in an Orthotopic
      Pancreatic Cancer Model.
AB  - Longitudinal monitoring of tumor size in vivo can provide important biological
      information about disease progression and treatment efficacy that is not captured
      by other modes of quantification. Ultrasound enables high-throughput evaluation
      of orthotopic mouse models via fast acquisition of three-dimensional tumor images
      and calculation of volume with a reasonable degree of accuracy. Herein, we
      compare orthotopic pancreatic tumor volume measurements determined by ultrasound
      with volume measured by calipers and tumor weight, and found strong correlations
      between the three modalities over a large range of tumor sizes, suggesting
      ultrasound can accurately quantify tumor volumes in this model. Furthermore, we
      demonstrate the unique ability of longitudinal treatment monitoring to reveal a
      tumor size-dependent response to Benzoporphyrin Derivative photodynamic therapy
      (BPD-PDT) and irinotecan. Small tumors (5-35 mm3 ) were found to respond well to
      a single round of PDT, while large tumors (35-65 mm3 ) showed no response to the
      same treatment. These results highlight the role that tumor size can play in
      preclinical interpretation of treatment response and more generally suggest that
      careful evaluation of subtle biological features such as this must be carefully
      considered in order to grant a more comprehensive understanding of disease
      biology in vivo.

PMID- 30229943
TI  - Inbreeding of house dust mites, a tool for genomic studies and allergy-related
      applications.

PMID- 30229944
TI  - Dual edge apparatus and algorithm for measurement of x-ray beam spot parameters.
AB  - PURPOSE: The shape, size, and location of the x-ray beam spot (where the electron
      beam strikes the target) in a linac-based radiation therapy machine are of
      potential clinical significance. Established techniques to measure the beam spot
      parameters involve specialized hardware and typically assess size and shape of
      the beam spot or its position, but not both. A simple apparatus and algorithm for
      measuring all beam spot parameters simultaneously is proposed here. METHODS: The
      apparatus is composed of two partially transmitting edge plates mounted at
      different vertical positions. The mount for the apparatus slides into the
      accessory tray of the linac treatment head so that it rotates with the
      collimator, and it is imaged by the existing electronic portal imaging device
      (EPID) over multiple collimator angles. A software algorithm takes the acquired
      images and uses a parallel-beam CT reconstruction technique to compute beam spot
      size, shape, and position in one computation. In addition, the wobble of the
      collimator assembly can be estimated. The overall method was validated with both
      Monte Carlo simulation and with comparison to in-house spot camera measurements
      on a radiation therapy system. RESULTS: The algorithm correctly predicted the
      beam spot parameters used for the Monte Carlo simulation to better than 50 MUm
      accuracy in all cases. Furthermore, results from the dual edge method matched
      spot camera results with 30 MUm accuracy for beam spot size and shape, with 80
      MUm average accuracy for beam spot position, and better than 200 MUm accuracy for
      collimator assembly wobble. CONCLUSIONS: We have developed a combination dual
      edge apparatus and image processing algorithm that, when used on a radiotherapy
      linac with an EPID, can accurately determine the size and shape of the electron
      beam spot, its position relative to collimator rotation axis, and the wobble of
      the collimator assembly.

PMID- 30229945
TI  - Measures of cutaneous pain perception and nociceptor density: More than skin
      deep.

PMID- 30229947
TI  - Soil-transmitted helminth parasites and allergy: Observations from Ecuador.
AB  - There is considerable interest as to potential protective effects of soil
      transmitted helminths (STH) against allergy and allergic diseases. Here, we
      discuss findings of studies done of the effects of STH parasites on atopy and
      allergic diseases in Ecuador. While cross-sectional studies have consistently
      shown a reduced prevalence of allergen skin prick test (SPT) reactivity among
      infected schoolchildren, the removal of these infections by repeated deworming
      did not affect SPT prevalence over the short-term (ie, 12 months) but may have
      increased SPT prevalence over the long-term (ie, 15-17 years). In the case of
      allergic symptoms, cross-sectional studies have generally not shown associations
      with STH and intervention studies showed no impact on prevalence. However, a
      birth cohort suggested that early STH infections might reduce wheeze by 5 years.
      Allergic sensitization to Ascaris, however, explained a significant proportion of
      wheezing among rural schoolchildren. Studies of the effects of STH on immune and
      inflammatory responses indicated a potential role of STH in contributing to more
      robust regulation. The effects of STH on allergy are likely to be determined by
      history of exposure over the life-course and by interactions with a wide variety
      of other infectious and non-infectious factors.

PMID- 30229948
TI  - Sibling bullying at 12 years and high-risk behavior in early adulthood: A
      prospective cohort study.
AB  - Emerging evidence suggests that sibling aggression is associated with the
      development of high-risk behavior. This study investigated the relationship
      between sibling bullying perpetration and victimization in early adolescence and
      high-risk behavior in early adulthood. Sibling bullying was assessed at 12 years
      in 6,988 individuals from the Avon Longitudinal Study of Parents and Children, a
      birth cohort based in the UK and high-risk behavioral outcomes were assessed at
      18-20 years. Frequent sibling bullying perpetration predicted antisocial behavior
      (OR = 1.74; 95%CI, 1.38-2.20), while frequent sibling bullying victimization
      increased the odds of nicotine dependence (OR = 2.87; 95%CI, 1.55-5.29), even
      after accounting for peer bullying and parent maltreatment. Categorical analysis
      revealed that particularly bullies and bully-victims were at risk of developing
      high-risk behavior. Finally, this study found that adolescents who were involved
      in bullying perpetration across multiple contexts (home and school) had the
      highest odds of reporting antisocial behavior (OR = 3.05; 95%CI, 2.09-4.44),
      criminal involvement (OR = 2.12; 95%CI, 1.23-3.66), and illicit drug use (OR =
      2.11; 95%CI, 1.44-3.08). Findings from this study suggest that sibling bullying
      perpetration may be a marker of or a contributory factor along the developmental
      trajectory to antisocial behavior problems. Intervention studies are needed in
      order to test whether reducing sibling bullying can alleviate long-term adverse
      social and behavioral outcomes.

PMID- 30229946
TI  - Performance/outcomes data and physician process challenges for practical big data
      efforts in radiation oncology.
AB  - It is an exciting time for big data efforts in radiation oncology. The use of big
      data to help aid both outcomes and decision-making research is becoming a
      reality. However, there are true challenges that exist in the space of gathering
      and utilizing performance and outcomes data. Here, we summarize the current state
      of big data in radiation oncology with respect to outcomes and discuss some of
      the efforts and challenges in radiation oncology big data.

PMID- 30229949
TI  - Distribution of the Epstein-Barr virus in the normal stomach and gastric lesions
      in Thai population.
AB  - The Epstein-Barr virus (EBV) is one of the infectious agents found in stomach
      tissue. Recently, EBV-associated gastric carcinoma (EBVaGC) was classified as a
      new subtype of gastric carcinoma. To date, there is a lack of knowledge about the
      distribution and prevalence of EBV infection in both the normal stomach and
      various gastric lesions, including EBVaGC, in the Thai population. In this study,
      we detected EBV in the normal stomach (NS; n = 19), chronic gastritis (CG; n =
      36), intestinal metaplasia (IM; n = 40), gastric dysplasia (GD; n = 15), and
      gastric adenocarcinoma (GC; n = 33) by polymerase chain reaction (PCR)
      amplification of the latent membrane protein (LMP1) gene of EBV. EBV-PCR
      amplification was positive in 42.1%, 36.1%, 22.5%, 13.3%, and 33.3% of NS, CG,
      IM, GD, and GC, respectively. For further clarification in EBVaGC, we performed
      EBV-encoded small RNA in situ hybridization (EBER-ISH) in PCR-positive cases of
      GD and GC. Four GC cases were EBER-ISH positive (12.1%), while both GD cases were
      EBER-ISH negative. In addition, we determined the distribution of the EBV strain
      (type A or B) based on EBNA3C sequence and EBV variants based on LMP1 variation
      (wild-type and 30-bp deletion variants; wt-LMP1 or del-LMP1). The results showed
      that type A and wt-LMP1 were the most prevalent in all lesions. In conclusion,
      EBV is common in both the NS and gastric lesions, and the frequency of EBVaGC was
      12.1% in Thai patients.

PMID- 30229950
TI  - Development and preliminary evaluation of a new screening instrument for atypical
      odontalgia and persistent dentoalveolar pain disorder.
AB  - AIM: To develop and preliminarily evaluate a new screening instrument for
      atypical odontalgia (AO) or persistent dentoalveolar pain disorder (PDAP). To
      evaluate the instrument's performance in detecting AO/PDAP amongst a
      heterogeneous group of orofacial pain conditions and pain-free controls and
      empirically compare its performance with an established neuropathic screening
      instrument (S-LANSS), which is the best available standard. METHODS: The study
      design was cross-sectional; subjects recruited included a convenience sample of
      pain-free controls (n = 21) and four groups of orofacial pain conditions: AO/PDAP
      (n = 22); trigeminal neuralgia (n = 21); temporomandibular disorder (n = 41); and
      acute dental pain (n = 41). The instrument's internal reliability and factor
      structure were examined alongside its sensitivity and specificity and ROC
      determined threshold score. RESULTS: The 9 AO/PDAP-specific items were found to
      moderately correlate with the S-LANSS (r = 0.58; P < 0.01). The 14-items of the
      full instrument were examined using exploratory factor analysis and reduced to
      ten items in a two-factor structure that explained 96% of the variance. This 10
      item final instrument had a ROC area of 0.77 (95% CI: 0.67; 0.88), sensitivity of
      77% (95% CI: 55; 92%), and specificity of 69% (95% CI: 60; 77%) with an
      intentionally higher false-positive rate than false-negative rate. In contrast,
      the S-LANSS exhibited sensitivity of 32% (95% CI: 14;55%) and specificity of 78%
      (95% CI: 70;85%) with less optimal false-positive versus false-negative rates.
      CONCLUSION: This preliminary study confirms the new screening instrument for
      AO/PDAP merits progression to field testing.

PMID- 30229951
TI  - Comparative evaluation of autocontouring in clinical practice: A practical method
      using the Turing test.
AB  - PURPOSE: Automated techniques for estimating the contours of organs and
      structures in medical images have become more widespread and a variety of
      measures are available for assessing their quality. Quantitative measures of
      geometric agreement, for example, overlap with a gold-standard delineation, are
      popular but may not predict the level of clinical acceptance for the contouring
      method. Therefore, surrogate measures that relate more directly to the clinical
      judgment of contours, and to the way they are used in routine workflows, need to
      be developed. The purpose of this study is to propose a method (inspired by the
      Turing Test) for providing contour quality measures that directly draw upon
      practitioners' assessments of manual and automatic contours. This approach
      assumes that an inability to distinguish automatically produced contours from
      those of clinical experts would indicate that the contours are of sufficient
      quality for clinical use. In turn, it is anticipated that such contours would
      receive less manual editing prior to being accepted for clinical use. In this
      study, an initial assessment of this approach is performed with radiation
      oncologists and therapists. METHODS: Eight clinical observers were presented with
      thoracic organ-at-risk contours through a web interface and were asked to
      determine if they were automatically generated or manually delineated. The
      accuracy of the visual determination was assessed, and the proportion of contours
      for which the source was misclassified recorded. Contours of six different organs
      in a clinical workflow were for 20 patient cases. The time required to edit
      autocontours to a clinically acceptable standard was also measured, as a gold
      standard of clinical utility. Established quantitative measures of autocontouring
      performance, such as Dice similarity coefficient with respect to the original
      clinical contour and the misclassification rate accessed with the proposed
      framework, were evaluated as surrogates of the editing time measured. RESULTS:
      The misclassification rates for each organ were: esophagus 30.0%, heart 22.9%,
      left lung 51.2%, right lung 58.5%, mediastinum envelope 43.9%, and spinal cord
      46.8%. The time savings resulting from editing the autocontours compared to the
      standard clinical workflow were 12%, 25%, 43%, 77%, 46%, and 50%, respectively,
      for these organs. The median Dice similarity coefficients between the clinical
      contours and the autocontours were 0.46, 0.90, 0.98, 0.98, 0.94, and 0.86,
      respectively, for these organs. CONCLUSIONS: A better correspondence with time
      saving was observed for the misclassification rate than the quantitative contour
      measures explored. From this, we conclude that the inability to accurately judge
      the source of a contour indicates a reduced need for editing and therefore a
      greater time saving overall. Hence, task-based assessments of contouring
      performance may be considered as an additional way of evaluating the clinical
      utility of autosegmentation methods.

PMID- 30229952
TI  - Volume-Based vs Rate-Based Enteral Nutrition in the Intensive Care Unit: Impact
      on Nutrition Delivery and Glycemic Control.
AB  - BACKGROUND: Underfeeding with enteral nutrition (EN) is prevalent in intensive
      care units (ICUs) and associated with negative outcomes. This study evaluated the
      impact of volume-based EN (VBEN) vs rate-based EN (RBEN) on delivery of
      prescribed energy and protein, and glycemic control (GC). METHODS: This
      retrospective study included adult patients who require mechanical ventilation
      within 48 hours of ICU admission and with an RBEN (n = 85) or VBEN (n = 86) order
      for >=3 consecutive days during the first 12 ICU days. RESULTS: Patients
      receiving VBEN, vs RBEN, received more prescribed energy (RBEN, 67.6%; VBEN,
      79.6%; P < .001) and protein (RBEN, 68.6%; VBEN, 79.3%; P < .001). Multiple
      linear regression analyses confirmed VBEN was significantly associated with an
      8.9% increase in energy (P = .002) and 7.7% increase in protein (P = .004)
      received, after adjusting for age, Acute Physiology and Chronic Health Evaluation
      II score, duration of and initiation day for EN, and ICU admission location.
      Presence of hyperglycemia (P = .40) and glycemic variability (GV) (P = .99) were
      not different between the 2 groups. After adjusting for age, body mass index,
      diabetes history, primary diagnosis, and percent of days receiving
      corticosteroids, GC outcomes (presence of hyperglycemia, P = .27; GV, P = .67)
      remained unrelated to EN order type in multivariable regression models.
      CONCLUSION: VBEN, compared with RBEN, was associated with increased energy and
      protein delivery without adversely affecting GC. These results suggest VBEN is an
      effective, safe strategy to enhance EN delivery in the ICU.

PMID- 30229953
TI  - Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced
      Glycation End Products, Decreases During the Summer in Dialysis Patients.
AB  - Tissue advanced glycation end products (AGEs) are a measure of cumulative
      metabolic and oxidative stress and cytokine-driven inflammatory reactions. AGEs
      are thought to contribute to the cardiovascular complications of hemodialysis
      (HD) patients. Skin autofluorescence (SAF) is related to the tissue accumulation
      of AGEs and rises with age. SAF is one of the strongest prognostic markers of
      mortality in these patients. The content of AGEs is high in barbecue food. Due to
      the location in northern Sweden, there is a short intense barbecue season between
      June and August. The aim of this study was to investigate if seasonal variations
      in SAF exist in HD patients, especially during the barbecue season. SAF was
      measured noninvasively with an AGE Reader in 34 HD-patients (15 of those with
      diabetes mellitus, DM). Each time the median of three measures were used. Skin-AF
      was measured before and after each one HD at the end of February and May in 31
      patients (22 men/9 women); the end of May and August in 28 (20 m/8 w); the end of
      August and March in 25 (19 m/6 w). Paired statistical analyses were performed
      during all four periods (n = 23, 17 m/6 w); as was HbA1c of those with DM. There
      was at a median 5.6% increase in skin-AF during the winter period (February-May,
      P = 0.004) and a 10.6% decrease in the skin-AF during the summer (May-August, P <
      0.001). HbA1c in the DM rose during the summer (P = 0.013). In conclusion, skin
      AF decreased significantly during the summer. Future studies should look for
      favorable factors that prevent skin-AF and subsequently cardiovascular diseases.

PMID- 30229954
TI  - Prevalence of thyroid stimulating hormone dysfunction among sofosbuvir-treated
      HCV-infected patients: A real-world clinical experience.
AB  - Thyroid dysfunctions occur frequently among hepatitis C virus (HCV)-infected
      patients. Accumulating evidence has shown the higher incidence of thyroid
      dysfunctions in interferon-treated patients that was previously the standard of
      care therapy. However, the prevalence of thyroid disorders has not been studied
      in the recently developed interferon-free regimens or direct-acting antiviral
      (DAA) drugs-treated patients. We recruited 37 patients who had just completed 6
      months long sofosbuvir-based treatment, and 26 interferon-treated patients were
      also included in the study. Serum thyrotropin level of all participants was
      measured using VIDAS. We observed thyroid dysfunctions in both pegylated
      interferon-experienced and DAA drug-experienced patients but the prevalence of
      hyperthyroidism was found significantly higher in patients treated with
      interferon-based regimen as compared with interferon-free regimens. This high
      prevalence of hypothyroidism in patients with HCV posttreatment highlights the
      need for regular periodic screening of patients during the treatment.

PMID- 30229955
TI  - Prenatal aqueduct stenosis: Association with rhombencephalosynapsis and neonatal
      outcome.
AB  - BACKGROUND AND PURPOSE: To examine prenatal MRI and postnatal imaging in fetuses
      with congenital aqueductal stenosis (CAS) to determine the frequency of
      association of rhombencephalosynapsis (RES) and how it may affect neonatal
      intensive care unit (NICU) course. MATERIALS AND METHODS: A single center IRB
      approved retrospective study of children with CAS was performed. Prenatal MRI,
      postnatal images, and clinical data were reviewed. Statistical analysis was
      performed with SAS statistical software package version 9.3. RESULTS: Aqueduct
      obstruction was confirmed for all 30 participants. Hydrocephalus required
      shunting in all but one (97%). Fifteen neonates had CAS with
      rhomboencephalosynapsis (RES) (50%). Although neonatal course between the two
      groups was comparable, 53% of CAS with RES neonates required feeding assistance
      versus 20% in CAS only (P = 0.128). Shunting in the CAS with RES group occurred
      at average of 6 days of life versus CAS group at 55 days (P = 0.196). Biometry
      measurements showed a statistically significant decrease in pons antero-posterior
      diameter in both groups (CAS only P = 0.0049 and CAS with RES P = 0.0003) when
      compared with norms for gestational age. CONCLUSION: CAS has a high association
      with RES. Feeding assistance in the NICU and earlier neurosurgical intervention
      may be required in patients with CAS who also have RES.

PMID- 30229956
TI  - The physical and chemical disruption of human hair after bleaching - studies by
      transmission electron microscopy and redox proteomics.
AB  - OBJECTIVE: To understand the structural and chemical effects of cosmetic peroxide
      bleaching on human hair. METHODS: Human hair was progressively bleached using
      alkaline peroxide-persulphate treatment. Proteins lost through leaching were
      examined using amino acid analysis and mass spectrometric sequencing. Fibre
      damage was assessed using transmission electron microscopy, amino acid analysis
      and redox proteomics. RESULTS: Protein loss through leaching increased with
      bleaching severity. Leached proteins were not limited to the cuticle, but also
      included cortical intermediate filaments and matrix keratin-associated proteins.
      The leached proteins were progressively oxidized as bleaching severity increased.
      Bleached fibres demonstrated substantial damage to the cuticle layers and to the
      cortex. Extensive melanin granule degradation was present after the mildest
      bleach treatment. Protein oxidation in bleached fibres was principally in
      cortical intermediate filaments - the most abundant hair proteins - and targeted
      the sulphur-containing amino acids, particularly the conversion of cystine
      disulphide bonds to cysteic acid. CONCLUSION: Peroxide chemical treatments
      quickly access the cortex, causing untargeted oxidative damage across the fibre
      in addition to the desired loss of melanin. Peroxide ingress is likely
      facilitated by the considerable structural degradation caused to the cuticle
      layers of hair fibres. The consequences of the peroxide action within the cuticle
      and cortex are oxidation of the proteins, and subsequent protein loss from the
      fibre that correlates to bleaching severity.

PMID- 30229957
TI  - Application of capillary electrophoresis combined with conductometric and UV
      detection to monitor meteorite simulant bioleaching by Acidithiobacillus
      ferrooxidans.
AB  - The importance of microorganisms and biotechnology in space exploration and
      future planets colonization has been discussed in the literature. Meteorites are
      interesting samples to study microbe-mineral interaction focused on space
      exploration. The chemolithotropic bacterium Acidithiobacillus ferrooxidans has
      been used as model to understand the iron and sulfur oxidation. In this work,
      capillary electrophoresis with capacitively coupled contactless conductivity
      detection and UV detection was used to monitor bacterial growth in a meteorite
      simulant by measuring the conversion of Fe2+ into Fe+3 . The effect of Co2+ and
      Ni2+ (metals also found in meteorites) on the bacterial growth was also
      evaluated. The presented method allowed the analyses of all metals in a single
      run (less than 8 min). The background electrolyte was composted of 10 mmol/L
      alpha-hydroxyisobutyric acid/Histidine. For comparison purpose, the samples were
      also analyzed by UV-Vis spectrophotometry. The Fe2+ conversion into Fe3+ by A.
      ferrooxidans was observed up to 36 h with the growth rate constant of 0.19/h and
      0.21/h in Tuovinen and Kelly (T&K) and in meteorite simulant media, respectively.
      The developed method presents favorable prospect to monitor the growth of other
      chemolithotropic microorganisms for biotechnology applications.

PMID- 30229958
TI  - Not a matter of parental choice but of social justice obligation: Children are
      owed measles vaccination.
AB  - This article presents arguments that reframe the discussion on vaccination
      ethics. The correct starting point for discussions on vaccination ethics is not
      what society owes parents, but rather what society owes children. Drawing on the
      justice theory of Powers and Faden, two conclusions are defended by presenting
      and defending a set of arguments. First, a just society is obligated to protect
      its children against serious vaccine-preventable diseases such as measles through
      adequate levels of vaccination. Second, this obligation of the just society rests
      on identifiable individuals and institutions: parents, healthcare professionals,
      government, and vaccine producers have important obligations in this regard. This
      removes vaccination out of the realm of individual or parental discretion, and
      situates it in the realm of societal obligation. Children are owed vaccination,
      society is obligated to provide it. If parents cannot or will not provide it,
      society ought to respond.

PMID- 30229959
TI  - Dielectric relaxation spectroscopy of aqueous micellar electrolyte solutions: A
      novel application to infer Dukhin number and zeta potential of a micelle.
AB  - : The complex permittivities of aqueous SDS solutions, with and without the
      addition of sodium chloride (NaCl), are measured in the frequency range from 200
      MHz to 14 GHz. The SDS concentrations are chosen such that the SDS molecules
      aggregate to micelles. In this frequency range, the measured spectra allow for
      the identification of two different relaxation processes. That is, the relaxation
      of the water molecules at frequencies above 1 GHz and the micellar relaxation at
      frequencies lower than 1 GHz. It is found that the addition of NaCl to the system
      mostly affects the micellar relaxation process. In detail, the time constant as
      well as the amplitude of the relaxation decrease by adding NaCl. These effects
      are attributed to the change in the solution conductivity that changes the
      properties of the micelle's electrical double layer. We also extract the Dukhin
      number of the micelles as a function of surfactant and electrolyte content from
      the measurements. The Dukhin number is a dimensionless group that describes the
      influence of the surface conductivity on a phenomena. A regression between Dukhin
      numbers and free sodium ions is found so that all data collapses on a single
      curve independent of the surfactant concentration. The surface conductivity is a
      manifestation of the electrical double layer and we use the Bikerman equation to
      infer the zeta potential of the micelles. Comparison to literature data shows
      very good agreement and proves that dielectric relaxation spectroscopy can be
      engaged to infer the zeta potential of micelles. ABBREVIATIONS: CMC critical
      micelle concentration, DRS dielectric relaxation spectroscopy, EDL electrical
      double layer.

PMID- 30229960
TI  - Occupational allergic contact dermatitis caused by colophonium.
AB  - BACKGROUND: Colophonium is a common contact allergen that is present not only in
      household products but also in occupational settings. OBJECTIVES: To describe the
      sources of occupational exposure to colophonium and the occupations at risk of
      colophonium allergy. METHODS: We reviewed patch test files from the years 2002 to
      2017 at the Finnish Institute of Occupational Health for patients with allergic
      reactions to colophonium and abietic acid. We analysed the patch test, occupation
      and exposure data of 39 patients diagnosed with occupational allergic contact
      dermatitis (OACD) caused by colophonium. RESULTS: Of the patients examined for
      suspected occupational dermatitis, 4.6% (n = 118) reacted positively to
      colophonium. The majority of the OACD patients worked in the wood industry, as
      machinists, or were involved in soldering or agriculture. The most common
      occupational sources of exposure were coniferous wood and wood-derived materials,
      followed by glues, metalworking fluids, and soldering materials. Colophonium is
      not always mentioned in safety data sheets (SDSs), and the sources of colophonium
      exposure are often materials for which there are no SDSs. CONCLUSION: OACD caused
      by colophonium is quite common and occurs in a variety of occupations. SDSs
      provide poor information for exposure assessment. Patch testing with the
      patient's own materials was often useful in establishing the diagnosis.

PMID- 30229961
TI  - Mercury Levels and Risk Implications Through Fish Consumption on the Sinaloa
      Coasts (Gulf of California, Northwest Mexico).
AB  - Fish consumption is the major source of mercury to humans. Fetuses and children
      are the most sensitive groups of populations to the effects of mercury.
      Consequently, fish consumption by pregnant women, children, and women of
      childbearing age is of concern because of the effects of mercury exposure on
      human health. To assess mercury exposure in a population in northwest Mexico, the
      allowed daily consumption of fish (which indicates the maximum daily amount of
      fish that can be consumed without causing adverse noncarcinogenic effects) was
      calculated for the general population (GP) and fishing-related population (FRP).
      The studied groups for both sectors of the population were children A (3-10 years
      old), children B (11-15 years old), women of childbearing age (16-40 years old),
      and the rest of the population (men >=16 years old, and women >=41 years old).
      Mercury content in canned and frozen tuna, smoked marlin, tilapia, Pacific
      sierra, dolphinfish, and bullseye puffer ranged from 0.01 to 0.23 MUg/g wet
      weight; none of the values were above the limit set by Mexico. Regarding mercury
      concentrations and rates of fish consumption, the GP consumes 1.7-2.7 times the
      allowed daily consumption, and the FRP consumes 1.6-3.9 that limit. The risk
      analysis showed the children A and B groups from the GP and adults of FRP to be
      the highest percentage of the population at risk (approximately 35%). These
      results highlight the need for adequate strategies that consider mercury exposure
      as part of public health policies associated with fish consumption in Mexico.

PMID- 30229962
TI  - Gene set enrichment analysis of SNP data in dairy and beef cattle with bovine
      respiratory disease.
AB  - Bovine respiratory disease (BRD) is a complex disease that is associated with
      infection by bacterial and viral pathogens when cattle fail to adequately respond
      to stress. The objective of this study was to use gene set enrichment analysis of
      SNP data (GSEA-SNP) and a network analysis (ingenuity pathway analysis) to
      identify gene sets, genes within gene sets (leading-edge genes) and upstream
      regulators associated with BRD in pre-weaned dairy calves and beef feedlot
      cattle. BRD cases and controls were diagnosed using the McGuirk health scoring
      system. Holstein calves were sampled from commercial calf-raising facilities in
      California (1003 cases and 1011 controls) and New Mexico (376 cases and 372
      controls). Commercial feedlot cattle were sampled from Colorado (500 cases and
      499 controls) and Washington (504 cases and 497 controls). There were 102 and 237
      unique leading-edge genes identified in the dairy calf and beef cattle
      populations respectively. Six leading-edge genes (ADIPOQ, HTR2A, MIF, PDE6G,
      PRDX3 and SNCA) were associated with BRD in both dairy and beef cattle. Network
      analysis identified glucose as the most influential upstream regulator in dairy
      cattle, whereas in beef cattle, TNF was the most influential upstream regulator.
      The genes, gene sets and upstream regulators associated with BRD have common
      functions associated with immunity, inflammation and pulmonary disease and
      provide insights into the mechanisms that are critical to BRD susceptibility in
      cattle.

PMID- 30229963
TI  - A case of canine high-grade T-cell lymphoma immunophenotypically consistent with
      T-zone lymphoma.
AB  - A 9-year-old spayed female Curly Coated Retriever was referred for evaluation of
      generalized peripheral lymphadenomegaly. The dog was clinically healthy on
      presentation with no anomalies detected on complete blood count, serum
      biochemistry, urinalysis, or three-view thoracic radiographs. Fine-needle
      aspiration (FNA) and cytology of the peripheral lymph nodes were consistent with
      lymphoma with an intermediate-sized lymphoid population. Flow cytometry of
      peripheral lymph nodes was consistent with a homogeneous population of CD4+ T
      cells that had lost expression of the pan-leukocyte antigen CD45. Variable
      expression of CD21, CD25, and class II major histocompatibility complex (MHC)
      were also noted. This was considered consistent with T-zone lymphoma (TZL),
      although the T cells were noted to be larger than usual based on flow cytometry.
      Due to the suspected indolent nature of this patient's disease and clinical
      progression, a careful monitoring approach was initially discussed with the
      owner. However, additional diagnostic testing was performed to confirm the
      diagnosis. Bone marrow cytology did not show any significant anomalies. The
      largest lymph node (left mandibular) was extirpated and submitted for
      histopathology. Based on the lymph node architecture, cellular features, and high
      mitotic activity, an unexpected diagnosis of peripheral T-cell lymphoma not
      otherwise specified (PTCL-NOS) was made. The dog was started on CHOP
      (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. This
      case illustrates the limitations of using flow cytometry as the sole means of
      diagnosing TZL and highlights the importance of using complementary tests when
      subtyping canine lymphoma, which is significant when considering a patient's
      treatment plan and prognosis.

PMID- 30229964
TI  - Trapping DNA with a high throughput microfluidic device.
AB  - Long strands of DNA can be trapped and concentrated near the inlet of a
      microfluidic channel by applying a pressure gradient and an opposing electric
      field. The mechanism for trapping involves a migration of DNA perpendicular to
      both the fluid flow and the electric field. Migration leads to a highly
      nonuniform distribution of DNA within a cross section of the channel, with the
      bulk of the DNA concentrated in a thin (10 MUm) layer next to the walls of the
      channel. This highly concentrated layer generates an electrophoretic flux toward
      the inlet to the device, despite the much larger fluid flow in the opposite
      direction. In this paper, the extent to which DNA can be trapped and concentrated
      by this means has been characterized by fluorescence measurements. At short times
      (<2 hours) nearly all the incoming DNA remains trapped within the device until
      the electric field is turned off. The DNA largely accumulates near the inlet, but
      after 30-60 minutes additional DNA starts to accumulate deeper into the channel.
      Eventually DNA leaks from the device itself, but ~80% of the incoming DNA can be
      retained for up to 5 hours. Optimizing the electric field strength can increase
      the amount of DNA that can be trapped, but the efficiency is not affected by the
      channel cross-section.

PMID- 30229965
TI  - Influence of crop residues, matric potential and temperature on growth of
      Exserohilum turcicum an emerging maize pathogen in Argentina.
AB  - Northern corn leaf blight (NCLB) caused by Exserohilum turcicum is an endemic
      foliar disease in the Argentinean maize production area. Before applying a
      control method, it is essential to focus on factors that lead to the survival and
      conservation of E. turcicum inoculum. However, there is little information about
      the life cycle of this emerging pathogen in our country. The objective of the
      present work was to analyse the growth ability of three E. turcicum isolates
      under different type and conditions of maize, wheat and soybean residues, matric
      potential, temperature and their interactions. Statistical analysis demonstrated
      a significant effect of three factors on growth rate: residues-based media,
      matric potential and temperature. Among them the major effect was produced by
      matric potential followed by temperature. Although there were no significant
      differences in the growth rate among different residues types, the range of
      conditions in which growth occurred was different. According to these results,
      soybean residues would allow a better survival of E. turcicum inoculum under no
      tillage system and providing an inoculum source for maize infections in
      subsequent year. SIGNIFICANCE AND IMPACT OF THE STUDY: Exserohilum turcicum is an
      emerging pathogen in Argentina that has caused significant economic losses in
      different maize growing areas. However, at present there is a lack of information
      about the life cycle of this fungal pathogen. The present study shows the
      influence of abiotic factors such as temperature and water potential on the
      growth of E. turcicum on different crop residues used in rotations with maize
      under no-till system cultivation. According to our results, soybean residues
      allowed the pathogen growth in a wider range of conditions compared to wheat and
      maize residue, providing an inoculum source for maize infections in subsequent
      season.

PMID- 30229966
TI  - Assessing the effect of triethyleneglycol dimethacrylate on tissue repair in 3D
      organotypic cultures.
AB  - Leachables from dental restoratives induce toxicity in gingival and pulp tissues
      and affect tissue regeneration/healing. Appropriate testing of these materials
      requires a platform that mimics the in vivo environment and allows the
      architectural self-assembly of cells into tissue constructs. In this study, we
      employ a new 3D model to assess the impact of triethyleneglycol dimethacrylate
      (TEGDMA) on early organization and advanced recruitment/accumulation of
      immortalized mouse gingival fibroblasts (GFs) and dental papilla mesenchymal
      cells (DPMCs) in extracellular matrix. We hypothesize that TEGDMA (1) interferes
      with the developmental architecture of GFs and DPMCs, and (2) inhibits the
      deposition of mineral. To test these hypotheses, GFs and DPMCs were incubated
      with the soluble TEGDMA at concentrations (0-2.5) mmol/L. Diameter and thickness
      of the constructs were determined by microscopic analysis. Cell differentiation
      was assessed by immunocytochemistry and the secreted mineral detected by alizarin
      red staining. TEGDMA interfered with the development of GFs and/or DPMCs
      microtissues in a dose-dependent manner by inhibiting growth of inter-spherical
      cell layers and decreasing spheroid size (four to six times). At low/moderate
      TEGDMA levels, GFs organoids retained their structures while reducing thickness
      up to 21%. In contrast, at low TEGDMA doses, architecture of DPMC organoids was
      altered and thickness decreased almost twofold. Overall, developmental ability of
      TEGDMA-exposed GFs and DPMCs depended on TEGDMA level. GFs constructs were more
      resistant to structural modifications. The employed 3D platform was proven as an
      efficient tool for quantifying the effects of leachables on tissue repair
      capacities of gingiva and dental pulp.

PMID- 30229967
TI  - Open source capillary electrophoresis.
AB  - Open source paradigm is becoming widely accepted in scientific communities and
      open source hardware is finding its steady place in chemistry research. In this
      review article, we provide the reader with the most up-to-date information on
      open source hardware and software resources enabling the construction and
      utilization of an "open source capillary electrophoresis instrument". While CE is
      still underused as a separation technique, it offers unique flexibility, low
      cost, and high efficiency and is particularly suitable for open source
      instrumental development. We overview the major parts of CE instruments, such as
      high voltage power supplies, detectors, data acquisition systems, and CE software
      resources with emphasis on availability of the open source information on the web
      and in the scientific literature. This review is the first of its kind, revealing
      accessible blueprints of most parts from which a fully functional open source CE
      system can be built. By collecting the extensive information on open source
      capillary electrophoresis in this review article, the authors aim at facilitating
      the dissemination of knowledge on CE within and outside the scientific community,
      fosters innovation and inspire other researchers to improve the shared CE
      blueprints.

PMID- 30229968
TI  - Modeling the Effectiveness of Respiratory Protective Devices in Reducing
      Influenza Outbreak.
AB  - Outbreaks of influenza represent an important health concern worldwide. In many
      cases, vaccines are only partially successful in reducing the infection rate, and
      respiratory protective devices (RPDs) are used as a complementary countermeasure.
      In devising a protection strategy against influenza for a given population,
      estimates of the level of protection afforded by different RPDs is valuable. In
      this article, a risk assessment model previously developed in general form was
      used to estimate the effectiveness of different types of protective equipment in
      reducing the rate of infection in an influenza outbreak. It was found that a 50%
      compliance in donning the device resulted in a significant (at least 50%
      prevalence and 20% cumulative incidence) reduction in risk for fitted and
      unfitted N95 respirators, high-filtration surgical masks, and both low-filtration
      and high-filtration pediatric masks. An 80% compliance rate essentially
      eliminated the influenza outbreak. The results of the present study, as well as
      the application of the model to related influenza scenarios, are potentially
      useful to public health officials in decisions involving resource allocation or
      education strategies.

PMID- 30229969
TI  - Population structure, genetic diversity and selection signatures within seven
      indigenous Pakistani goat populations.
AB  - Goat farming in Pakistan depends on indigenous breeds that have adapted to
      specific agro-ecological conditions. Pakistan has a rich resource of goat breeds,
      and the genetic diversity of these goat breeds is largely unknown. In this study,
      genetic diversity and population structure were characterized from seven
      indigenous goat breeds using the goat 50K SNP chip. The genetic diversity
      analysis showed that Bugi toori goats have the highest inbreeding level,
      consistent with the highest linkage disequilibrium, lowest diversity and long run
      of heterozygosity segments. This indicates that this breed should be prioritized
      in future conservation activities. The population structure analysis revealed
      four fairly distinct clusters (including Bugi toori, Bari, Black Tapri and some
      Kamori) and three other breeds that are seemingly the results of admixture
      between these or related groups (some Kamori, Pateri, Tapri and White Tapri). The
      selection signatures were evaluated in each breed. A total of 2508 putative
      selection signals were reported. The 26 significant windows were identified in
      more than four breeds, and selection signatures spanned several genes that
      directly or indirectly influence traits included coat colour variation (KIT),
      reproduction (BMPR1B, GNRHR, INSL6, JAK2 and EGR4), body size (SOCS2), ear size
      (MSRB3) and milk composition (ABCG2, SPP1, CSN1S2, CSN2, CSN3 and PROLACTIN).

PMID- 30229970
TI  - Fine-tuning of SIRT1 expression is essential to protect the liver from
      cholestatic liver disease.
AB  - : Cholestasis comprises aetiologically heterogeneous conditions characterized by
      accumulation of bile acids in the liver that actively contribute to liver damage.
      Sirtuin 1 (SIRT1) regulates liver regeneration and bile acid metabolism via
      modulating the farnesoid X receptor (FXR); we here investigate its role in
      cholestatic liver disease. We determined SIRT1 expression in livers from patients
      with cholestatic disease, in two experimental models of cholestasis, as well as
      in human and murine liver cells in response to bile acid loading. SIRT1
      overexpressing (SIRToe ) and hepatocyte-specific SIRT1-KO mice (SIRThep-/- ) were
      subjected to BDL and were fed with 0.1%DDC diet to determine the biological
      relevance of SIRT1 during cholestasis. The effect of NorUDCA was tested in
      BDL/SIRToe mice. We found that SIRT1 was highly expressed in livers from
      cholestatic patients, mice after BDL and Mdr2-/- animals. The detrimental effects
      of SIRT1 during cholestasis were validated in vivo and in vitro. SIRToe mice
      showed exacerbated parenchymal injury whereas SIRThep-/- mice evidenced a
      moderate improvement after BDL and 0.1%DDC feeding. Likewise, hepatocytes
      isolated from SIRToe mice showed increased apoptosis in response to bile acids,
      while a significant reduction was observed in SIRThep-/- hepatocytes.
      Importantly, the decrease, but not complete inhibition of SIRT1 exerted by
      NorUDCA treatment correlated with pronounced improvement in liver parenchyma in
      BDL/SIRToe mice. Interestingly, both SIRT1 overexpression and hepatocyte-specific
      SIRT1 depletion correlated with inhibition of the farnesoid X receptor (FXR),
      whereas modulation of SIRT1 by NorUDCA associated with restored FXR-signalling.
      CONCLUSION: SIRT1 expression is increased during human and murine cholestasis.
      Fine-tuning expression of SIRT1 is essential to protect the liver from
      cholestatic-liver damage. This article is protected by copyright. All rights
      reserved.

PMID- 30229971
TI  - Clinical efficacy and safety of sodium cantharidinate plus chemotherapy in non
      small-cell lung cancer: A systematic review and meta-analysis of 38 randomized
      controlled trials.
AB  - WHAT IS KNOWN AND OBJECTIVE: Sodium cantharidinate has been widely used in lung
      cancer treatment in China. To investigate whether sodium cantharidinate improves
      clinical effectiveness in non-small-cell lung cancer, we systematically re
      evaluated all related studies. METHODS: All studies of cantharidinate for non
      small-cell lung cancers (NSCLC) were selected from the MEDLINE, EMBASE, Web of
      Science (ISI), China National Knowledge Infrastructure Database (CNKI), Chinese
      Scientific Journals Full-Text Database (VIP), Wanfang, China Biological Medicine
      Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese
      clinical trial registry (Chi-CTR), WHO International Clinical Trials Registry
      Platform (WHO-ICTRP) and US-clinical trials databases (established to September
      2017). Their quality was evaluated using the Cochrane evaluation handbook of
      randomized controlled trials (RCTs) (5.1.0). The data were extracted following
      PICO principles and synthesized through meta-analysis. RESULTS AND DISCUSSION: We
      included 38 trials involving 2845 patients, but most trials had an unclear risk
      of bias. Sodium cantharidinate could increase the objective response rate (ORR)
      (1.52, (1.40-1.66]), disease control rate (DCR) (1.20, [1.16-1.25]) and quality
      of life (QOL) (1.76, [1.56-1.98]), but not the 1-year overall survival (OS) rate
      (1.16, [0.91-1.47]) and the 2-year OS rate (1.21, [0.51-2.91]). Subgroup analysis
      revealed that sodium cantharidinate and vitamin B6 at 0.5, 0.4 or 0.3 mg, and
      cantharidinate at 0.5 mg could all increase the ORR and DCR. Cantharidinate
      therapy had a lower risk of neutropenia (0.58, [0.50-0.67]), thrombocytopenia
      (0.57, [0.45-0.72]), gastrointestinal reaction (0.65, [0.52-0.82]) and
      nausea/vomiting (0.56, [0.41-0.76]) than that of chemotherapy alone. Sensitivity
      analysis showed that the results had good robustness. WHAT IS NEW AND CONCLUSION:
      Current evidence reveals that sodium cantharidinate can improve tumour responses
      and QOL with a lower risk of haematotoxicity and gastrointestinal toxicity than
      chemotherapy alone in NSCLC. However, the evidence does not indicate that it can
      improve long-term survival rates.

PMID- 30229972
TI  - Noradrenaline for Hepatorenal Syndrome in Patients With Acute on Chronic Liver
      Failure: Hope Remains!

PMID- 30229973
TI  - From Ideal to Real Risk: Philosophy of Causation Meets Risk Analysis.
AB  - A question has been raised in recent years as to whether the risk field,
      including analysis, assessment, and management, ought to be considered a
      discipline on its own. As suggested by Terje Aven, unification of the risk field
      would require a common understanding of basic concepts, such as risk and
      probability; hence, more discussion is needed of what he calls "foundational
      issues." In this article, we show that causation is a foundational issue of risk,
      and that a proper understanding of it is crucial. We propose that some old ideas
      about the nature of causation must be abandoned in order to overcome certain
      persisting challenges facing risk experts over the last decade. In particular, we
      discuss the challenge of including causally relevant knowledge from the local
      context when studying risk. Although it is uncontroversial that the receptor
      plays an important role for risk evaluations, we show how the implementation of
      receptor-based frameworks is hindered by methodological shortcomings that can be
      traced back to Humean orthodoxies about causation. We argue that the first step
      toward the development of frameworks better suited to make realistic risk
      predictions is to reconceptualize causation, by examining a philosophical
      alternative to the Humean understanding. In this article, we show how our
      preferred account, causal dispositionalism, offers a different perspective in how
      risk is evaluated and understood.

PMID- 30229974
TI  - Tobacco product use among workers in the construction industry, United States,
      2014-2016.
AB  - BACKGROUND: Although cigarette smoking has declined among U.S. workers, smoking
      remains high among construction workers. This study assessed tobacco product use
      among U.S. construction workers. METHODS: The 2014-2016 National Health Interview
      Survey data for U.S. working adults were analyzed. RESULTS: Of the 10.2 (6.3% of
      working adults) million construction workers, 35.1% used any tobacco product;
      24.4% were cigarette smokers, 8.3% were cigar, cigarillo, pipe or hookah smokers,
      7.8% were smokeless tobacco users, 4.4% were e-cigarette users, and 7.6% used >=2
      tobacco product users. Tobacco use varied by worker characteristics, with highest
      tobacco use (>35%) among those reporting <=5 years on the job, temporary work
      status, job insecurity, or an unsafe workplace. Construction workers had higher
      odds of tobacco product use than non-construction workers. CONCLUSIONS: Over one
      third of U.S. construction workers use tobacco products and disparities exist
      across sub-groups. Workplace tobacco control strategies could reduce tobacco use
      among this population.

PMID- 30229976
TI  - News & Announcements: American Society for Laser Medicine and Surgery, Inc.

PMID- 30229975
TI  - Modeling the Airborne Infection Risk of Tuberculosis for a Research Facility in
      eMalahleni, South Africa.
AB  - A detailed mathematical modeling framework for the risk of airborne infectious
      disease transmission in indoor spaces was developed to enable mathematical
      analysis of experiments conducted at the Airborne Infections Research (AIR)
      facility, eMalahleni, South Africa. A model was built using this framework to
      explore possible causes of why an experiment at the AIR facility did not produce
      expected results. The experiment was conducted at the AIR facility from August
      31, 2015 to December 4, 2015, in which the efficacy of upper room germicidal
      ultraviolet (GUV) irradiation as an environmental control was tested. However,
      the experiment did not produce the expected outcome of having fewer infections in
      the test animal room than the control room. The simulation results indicate that
      dynamic effects, caused by switching the GUV lights, power outages, or
      introduction of new patients, did not result in the unexpected outcomes. However,
      a sensitivity analysis highlights that significant uncertainty exists with risk
      of transmission predictions based on current measurement practices, due to the
      reliance on large viable literature ranges for parameters.

PMID- 30229977
TI  - Clinical outcome and viral genome variability of hepatitis B virus induced acute
      liver failure (HEP-18-0579).
AB  - INTRODUCTION: Acute hepatitis B virus (HBV) infection remains a frequent cause of
      acute liver failure (ALF) worldwide. ALF occurs in 0.1-0.5% of infected patients.
      Aim of this study was to scrutinize the outcome of patients with HBV induced ALF
      and mutational patterns of HBV variants, which might contribute to ALF. METHODS:
      From 2005 to 2016, 42 patients were treated for HBV-induced ALF in the University
      Hospital Essen, Germany. Clinical and virological data from these patients were
      collected. As a control, 38 patients with acute hepatitis B (AHB) without liver
      failure were included. The HBV genome was sequenced by Next Generation Sequencing
      (NGS). Mutations that were found by NGS were analyzed in vitro. RESULTS: 8/42
      patients had ALF without spontaneous recovery (NSR): 7 patients underwent liver
      transplantation (LTx) and one patient died before LTx. 34/42 patients (81%) had
      spontaneous recovery (SR) and cleared the infection, achieving either anti-HBs
      seroconversion or HBsAg loss. HBV genotype (GT)-D was the most frequent GT in ALF
      patients. Mutations in HBV core, preS2 and SHB (small hepatitis B surface
      antigen) were more frequent in patients with ALF -non spontaneous recovery (NSR)
      compared to ALF-spontaneous recovery (SR) or AHB patients. Amino acid deletions
      (16-22 and 20-22) in preS2 and SHB mutation L49R were exclusively detected in ALF
      NSR patients. In vitro analyses reveal that these mutations did not influence
      HBsAg secretion or infectivity. CONCLUSIONS: HBV GT-D and increased variability
      in HBV core, preS2 region and SHB are associated with a worse clinical outcome of
      acute HBV infection. This article is protected by copyright. All rights reserved.

PMID- 30229978
TI  - Is it time to reconsider the Milan Criteria for selecting patients with
      hepatocellular carcinoma for deceased-donor liver transplantation?
AB  - Liver transplantation (LT) is considered the optimal treatment for hepatocellular
      carcinoma (HCC) because it removes tumor as well as the underlying cirrhotic
      liver. Due to a global organ shortage, LT for patients with HCC is limited to
      patients with expected survival comparable to that of non-malignant indications.
      Therefore, identifying patients with lower rates of HCC recurrence and higher
      rates of survival is critical. International guidelines have considered the Milan
      Criteria (MC) as the standard for selecting HCC patients for deceased donor LT
      (DDLT). However, several alternative criteria have been reported in the Western
      world. Interestingly, the two most recent models combining AFP level, number of
      nodules, and size of the largest nodule, have been shown to outperform MC in
      identifying patients with low risk of HCC recurrence or those who will survive
      for 5 years after liver transplantation. In addition, new models overcome
      limitations of MC in improving classification of high versus low risk patients
      with HCC for DDLT. These recent scoring systems also provide clinicians with user
      friendly tools to better identify patients at lower risk of recurrence. Although
      most Western countries still select patients based on MC, there is a mounting
      change in recent practice patterns regarding the selection of patients with HCC
      for DDLT. Herein, we describe how alternative criteria should lead to re
      consideration of MC as it applies to selecting patients with HCC for DDLT in
      international guidelines. This article is protected by copyright. All rights
      reserved.

PMID- 30229979
TI  - 3D-Printed PCL/rGO Conductive Scaffolds for Peripheral Nerve Injury Repair.
AB  - The incidence of peripheral nerve injuries is on the rise and the current gold
      standard for treatment of such injuries is nerve autografting. Given the severe
      limitations of nerve autografts which include donor site morbidity and limited
      supply, neural guide conduits (NGCs) are considered as an effective alternative
      treatment. Conductivity is a desired property of an ideal NGC. Reduced graphene
      oxide (rGO) possesses several advantages in addition to its conductive nature
      such as high surface area to volume ratio due to its nanostructure and has been
      explored for its use in tissue engineering. However, most of the works reported
      are on traditional 2D culture with a layer of rGO coating, while the native
      tissue microenvironment is three-dimensional. In this study, PCL/rGO scaffolds
      are fabricated using electrohydrodynamic jet (EHD-jet) 3D printing method as a
      proof of concept study. Mechanical and material characterization of the printed
      PCL/rGO scaffolds and PCL scaffolds was done. The addition of rGO results in
      softer scaffolds which is favorable for neural differentiation. In vitro neural
      differentiation studies using PC12 cells were also performed. Cell proliferation
      was higher in the PCL/rGO scaffolds than the PCL scaffolds. Reverse transcription
      polymerase chain reaction and immunocytochemistry results reveal that PCL/rGO
      scaffolds support neural differentiation of PC12 cells.

PMID- 30229980
TI  - Skewed X chromosome inactivation in girls and female adolescents with autoimmune
      thyroid disease.
AB  - OBJECTIVE: Skewed X chromosome inactivation (XCI) was associated with female
      predominance in adult autoimmune thyroid disease (ATD). In normal females, skewed
      XCI is increased with age. Whether early-onset skewed XCI is associated with
      childhood ATD remains unknown. This study aimed to determine XCI skewing in
      paediatric ATD. DESIGN, PATIENTS AND MEASUREMENTS: Ninety-one female ATD
      patients, aged 3-20 years and 57 age-matched, female controls were enrolled. XCI
      was analysed by enzymatic digestion of DNA with methylation-sensitive enzymes
      followed by PCR of the polymorphic CAG repeat in the androgen receptor gene.
      Skewed XCI was defined as having 80% or greater of the cells preferentially
      inactivated on the same X chromosome. XCI pattern of the enrolled patients and
      parental origin of the skewed XCI were determined. RESULTS: After exclusion of
      samples with homozygous CAG repeats, skewed XCI was analysed in 83 patients (57
      Graves' disease and 26 Hashimoto thyroiditis) and 52 controls. There was an
      increased frequency of skewed XCI in ATD patients as compared with the controls
      (23% vs 8%, P = 0.022). Patients with Hashimoto thyroiditis had greater frequency
      of skewed XCI than patients with Graves' disease (38% vs 16%, P = 0.023). There
      were no differences in clinical parameters between patients with skewed and
      random XCI. Analysis of 7 patients with skewed XCI showed a preferential
      inactivation of paternal X chromosome in 6 patients (86%). CONCLUSIONS: Frequency
      of skewed XCI was increased in childhood ATD. This observation suggests a
      possible association of skewed XCI in the development of paediatric ATD.

PMID- 30229981
TI  - Identification and diversity of Y-chromosome haplotypes in Qinghai yak
      populations.
AB  - The aim of the present study was to perform a preliminary analysis of the
      characterization and diversity of Y-chromosome haplotypes/haplogroups in yak of
      Qinghai Province, China. A total of 322 male yaks from nine populations belonging
      to three officially recognized breeds (Gaoyuan, Huanhu and Datong) were sampled.
      Animals were genotyped using six previously reported Y-SNPs present in the SRY,
      USP9Y, UTY, AMELY and OFD1Y genes and four new Y-SNPs in the OFD1Y gene
      (g.569A>C, g.578A>C, g.608G>T and g.653G>C) identified in this study. Seven Y
      chromosome haplotypes (H1-H7) were identified according to the combination of the
      10 Y-SNPs. H1, H2 and H6 were the most common and shared haplotypes across all
      yak populations/breeds. Private haplotypes H3 and H7 were detected in the Datong
      breed; H4 in Guoleimude, Qumalai, Qilian, Tianjun and Ganglong populations; and
      H5 in Qumalai of Gaoyuan breed. Haplotype clustering and network analyses
      inferred two haplogroups, Y1 and Y2, indicating two divergent lineages of
      paternal origins of Qinghai yak. The analysis of molecular variance showed a
      significant difference among individuals (P < 0.0001) with more than 93% of the
      total genetic variation present within populations, suggesting a weak genetic
      structure among Qinghai yak populations. The overall Y-haplotype diversity was
      0.538 +/- 0.028, showing a relatively high diversity in Qinghai yak. The Gaoyuan
      and Datong breeds had similar haplotype diversities (0.547 +/- 0.030 and 0.553 +/
      0.083, respectively), which were higher than that of the Huanhu breed (0.441 +/-
      0.098). Our results support the conservation and sustainable use of unique yak
      genetic resources in Qinghai.

PMID- 30229983
TI  - Elevated 1-hour post-load plasma glucose identifies obese youth with abnormal
      glucose metabolism and an unfavourable inflammatory profile.
AB  - CONTEXT: Adults with plasma glucose levels at one hour (1h-GL) >=8.6 mmol/L
      during an oral glucose tolerance test (OGTT) are at increased risk for type 2
      diabetes mellitus and present an unfavourable cardiometabolic and inflammatory
      profile, but relevant data on children are scarce. OBJECTIVE: To investigate if
      elevated 1h-GL during OGTT in obese children and adolescents is associated with
      insulin resistance and specific pro-inflammatory biomarkers. RESEARCH DESIGN AND
      METHODS: The study group comprised 88 obese children who attended the Outpatient
      Pediatric Clinic of our Hospital between January and December 2016. Children were
      divided into two groups according to 1h-GL during an OGTT: group 1 (n = 57)
      consisted of those with 1h-GL <8.6 mmol/L and group 2 (n = 31) of those with 1h
      GL >=8.6 mmol/L. Arterial blood pressure, body mass index (BMI) and waist
      circumference (WC) z-scores were measured in all participants. Specific insulin
      resistance (IR) indices, that is HOMA-IR, Matsuda index and Cederholm insulin
      sensitivity index (ISI) were calculated. Further, pro-inflammatory biomarkers
      that have been correlated with obesity complications, namely adiponectin, leptin,
      visfatin and interleukin (IL)-6 together with lipid levels were measured in all
      participants. Logistic regression analysis was used. RESULTS: Children in group 2
      had higher insulin (15.5 +/- 6.4 vs 10.9 +/- 4.8 MUU/mL), HOMA-IR (3.41 +/- 1.4
      vs 2.34 +/- 1.05) and lower Matsuda index [4.7 (3.1) vs 18.4 (17) median plus
      IQR] and Cederholm ISI (38 +/- 6 vs 56 +/- 11), than children in group 1 (all P <
      0.001). They also had higher visfatin (15.4 +/- 5.2 vs 10.1 +/- 7 ng/mL), and IL
      6 [12.5 (6.7) vs 4.8 (4.4) pg/mL], and lower adiponectin (5.9 +/- 3.4 vs 11.8 +/-
      4.7 MUg/mL) than children in group 1 (all P < 0.001). Logistic regression showed
      that these differences between the two groups were independent of age, sex,
      Tanner stage, BMI and WC z-scores. CONCLUSIONS: In obese children, 1h-GL >=8.6
      mmol/L during an OGTT is correlated with worsened IR, and an unfavourable
      metabolic and inflammatory profile. Thus, 1h-GL could be used as an additional
      marker to identify obese children and adolescents at increased risk of developing
      obesity complications.

PMID- 30229982
TI  - Factors associated with the efficacy of intravenous methylprednisolone in
      moderate-to-severe and active thyroid-associated ophthalmopathy: A single-centre
      retrospective study.
AB  - OBJECTIVE: Intravenous methylprednisolone (IVMP) is recommended as the first-line
      treatment for moderate-to-severe and active thyroid-associated ophthalmopathy
      (TAO). This study aimed to identify potential predictors and establish a
      multivariable prediction model for the efficacy of IVMP therapy. DESIGN: A single
      centre retrospective study. PATIENTS: A total of 302 consecutive patients
      diagnosed with moderate-to-severe and active TAO who underwent the full course of
      IVMP therapy were included. METHODS: Participants were sequentially divided into
      the training set (n = 200) and the validation set (n = 102). Multivariate
      logistic regression analysis was used to identify the independent predictors and
      establish the predictive model. RESULTS: In addition to the pretreatment clinical
      activity score (OR = 3.506, P < 0.001), elevated thyroid-stimulating hormone
      (TSH) levels during treatment (OR = 0.145, P = 0.005), pretreatment anti-TSH
      receptor antibody levels (OR = 0.061, P < 0.001) and duration of eye symptoms (OR
      = 0.878, P = 0.017), a significant relationship was found between therapeutic
      efficacy and the pretreatment triglyceride levels (OR = 0.090, P = 0.001). The
      prediction model showed good calibration and excellent discrimination, with an
      area under curve of 0.915 (P < 0.001) and 0.885 (P < 0.001) in the training and
      validation sets, respectively. CONCLUSIONS: This study provides some novel
      insights into the factors associated with the efficacy of IVMP therapy. A
      multivariable prediction model has been established and validated to help
      determine the indication and prognosis of IVMP therapy. Moreover, several
      suggestions have been made in the management of TAO patients: early diagnosis and
      treatment (within 15 months); prompt restoration and maintenance of euthyroidism,
      especially meticulous control of TSH levels (<=5 MUIU/mL); and regular monitoring
      of triglyceride levels.

PMID- 30229984
TI  - Psoriasin (S100A7) and koebserisin (S100A15) as potential markers of
      atherosclerosis in patients with psoriasis.

PMID- 30229985
TI  - Characterization of virulence properties and multi-drug resistance profiles in
      motile Aeromonas spp. isolated from zebrafish (Danio rerio).
AB  - Aeromonas spp. are opportunistic pathogenic bacteria associated with a multitude
      of diseases in ornamental fish. In this study, virulence properties and
      antibiotic resistance patterns of 43 Aeromonas strains isolated from 46 zebrafish
      were investigated. The isolates were identified as Aeromonas veronii biovar
      veronii (n = 26), A. veronii biovar sobria (n = 3), Aeromonas hydrophila (n = 8),
      A. caviae (n = 3), Aeromonas enteropelogenes (n = 2) and Aeromonas dhakensis (n =
      1) by gyrB gene sequencing. The sequence divergence within and between the
      species ranged from 0-5.80% and 4.90-8.00%. Each species formed a distinct group
      in a neighbour-joining phylogenetic tree. The lipase production, biofilm
      formation, DNase activity, gelatinase production, caseinase production and beta
      hemolysis were phenotypically observed in 34 (79.07%), 33 (74.74%), 30 (69.77%),
      25 (58.14%), 22 (51.18%) and 21 (48.84%) isolates. The virulence genes were
      detected by polymerase chain reaction (PCR) in following frequencies- aer
      (86.05%), hlyA (83.72%), gcaT (83.72%), lip (72.09%), act (67.44%), fla (65.12%),
      ascV (58.14%), ast (55.81%), ser (41.86%), ahyB (39.53%) and alt (25.58%). Every
      isolate was resistant to at least four antibiotics in disk diffusion test. The
      multiple antibiotic resistance (MAR) index values ranged from 0.22-0.50 among the
      isolates. Our study suggests that zebrafish can be a potential reservoir of
      virulent and multi-drug resistant Aeromonas spp. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Aeromonas spp. are Gram-negative and facultative anaerobic bacteria which
      are ubiquitous in aquatic environments. Virulence properties and antibiotic
      resistance of ornamental fish-borne Aeromonas spp. are poorly understood. The
      virulence factors as well as multiple antibiotic resistance profiles of zebrafish
      borne Aeromonas spp. were characterized for the first time in Korea. Most of the
      isolates were positive for phenotypic virulence traits and harboured several
      virulence genes revealing the virulence potential of zebrafish-borne Aeromonas
      spp. Additionally, the high multiple antibiotic resistance (MAR) index values
      displayed by the isolates highlight the necessity of responsible use of
      antibiotics in the ornamental fish industry.

PMID- 30229987
TI  - Reply.

PMID- 30229986
TI  - The effects of iprodione fungicide on survival, behavior, and brood development
      of honeybees (Apis mellifera L.) after one foliar application during flowering on
      mustard.
AB  - A semifield study to assess the effects of iprodione on honeybees at label use
      rates was conducted on a bloom mustard crop. The present study followed the
      Organisation for Economic Co-operation and Development guideline 75 tunnel test
      and consisted of 3 groups: the iprodione-treated group, the untreated control
      group, and the toxic reference item group. In addition to the tunnels used for
      biological assessments, a tunnel was set up in the treatment and control groups
      to determine the level of residues in flowers, nectar, and pollen. The major
      endpoints to assess the effects of the application of iprodione were mortality,
      flight intensity, behavior, condition of the colonies, and development of the
      brood. Residue analysis showed that honeybees were exposed to significant
      residues of iprodione. However, no adverse effects were observed on overall
      mortality, flight intensity, behavior, or brood development of honeybees compared
      to control. It is concluded that iprodione does not adversely affect the health
      of honeybees when applied in agriculture at commercially relevant rates in a
      worst-case exposure scenario. Environ Toxicol Chem 2018;37:3086-3094. (c) 2018
      SETAC.

PMID- 30229988
TI  - Dual excitatory and smooth muscle-relaxant effect of beta-phenylethylamine on
      gastric fundus strips in rats.
AB  - beta-Phenylethylamine (beta-PEA) is a trace amine with chemical proximity to
      biogenic amines and amphetamines. It is an endogenous agonist of trace amine
      associated receptors (TAARs) that acts as a neuromodulator of classic
      neurotransmitters in the central nervous system. At high concentrations, beta-PEA
      contracts smooth muscle, and a role for TAARs in these responses has been
      postulated. The high dietary intake of trace amines has been associated with such
      symptoms as hypertension and migraine, especially after the intake of foods
      containing such compounds. In gastrointestinal tissues, TAAR expression was
      reported, although the effect of beta-PEA on gastric contractile behaviour is
      unknown. Here, isolated strips that were obtained from the rat gastric fundus
      were stimulated with high micromolar concentrations of beta-PEA. Under resting
      tonus, beta-PEA induced contractions. In contrast, when the strips were
      previously contracted with KCl, a relaxant response to beta-PEA was observed. The
      contractile effect of beta-PEA was inhibited by 5-hydroxytryptamine (5-HT)
      receptor antagonists (i.e., cyproheptadine and ketanserin) but not by the TAAR1
      antagonist EPPTB. In gastric fundus strips that were previously contracted with
      80 mmol/L KCl, the relaxant effect of beta-PEA intensified in the presence of 5
      HT receptor antagonists, which was inhibited by EPPTB and the adenylyl cyclase
      inhibitor MDL-12,330A. The guanylyl cyclase inhibitor ODQ did not alter the
      relaxant effects of beta-PEA. In conclusion, beta-PEA exerted dual contractile
      and relaxant effects on rat gastric fundus. The contractile effect appeared to
      involve the recruitment of 5-HT receptors, and the relaxant effect of beta-PEA on
      KCl-elicited contractions likely involved TAAR1 .

PMID- 30229989
TI  - Prevalence and impact of de novo DSA during a multicenter immunosuppression
      withdrawal trial in adult liver transplant recipients.
AB  - : The development of HLA donor-specific antibody/antibodies (DSA) is not well
      described in liver transplant (LT) patients undergoing immunosuppression (IS)
      withdrawal protocols despite the allograft risk associated with de novo DSA
      (dnDSA). We analyzed the development of dnDSA in 69 LT patients who received
      calcineurin inhibitor monotherapy and were enrolled in the ITN030ST study. Of
      these 69 patients, 40 stable patients were randomized to IS maintenance (n=9) or
      IS minimization (n=31). Nine of the 31 IS minimization patients achieved complete
      withdrawal and were free of IS. Among patients who achieved stable IS monotherapy
      1 year after transplantation, the prevalence of dnDSA was 18.8%. Acute rejections
      and the biopsy-proven findings disqualifying patients from IS withdrawal attempt
      were factors associated with dnDSA development (p=0.011 and p=0.041,
      respectively). Among randomized patients, dnDSA prevalence was 51.7% after IS
      minimization and 66.7% in IS free patients. dnDSA prevalence in patients on IS
      maintenance was 44.4%. dnDSA development during IS minimization was a risk factor
      for acute rejection (p=0.015). The majority of dnDSA were against HLA-DQ antigens
      (78.7%). CONCLUSION: During the first year following transplantation, acute
      rejections increased the risk of developing dnDSA. Therefore, dnDSA positivity
      should be considered for IS withdrawal eligibility. During IS minimization, dnDSA
      development was associated with acute rejection, which prevented further IS
      withdrawal attempts. This article is protected by copyright. All rights reserved.

PMID- 30229990
TI  - Prevalence and degree of insulin resistance in Chinese Han women with PCOS:
      Results from euglycemic-hyperinsulinemic clamps.
AB  - OBJECTIVE: The euglycemic-hyperinsulinemic clamp is the gold standard to evaluate
      insulin resistance (IR), but there are only a few studies on the prevalence of IR
      in Chinese Han women with polycystic ovary syndrome (PCOS). This study
      investigated: (a) the prevalence of IR in Chinese Han women with PCOS by clamp,
      (b) the degree of reduction in insulin sensitivity (IS) and the contribution of
      body mass index (BMI). DESIGN: Retrospective cross-sectional analysis. PATIENTS:
      Chinese Han women with PCOS (n = 448) visiting the Department of Endocrinology or
      the Department of Obstetrics and Gynaecology of the First Affiliated Hospital of
      Chongqing Medical University. Chinese Han women without PCOS (controls) from the
      same area (n = 40). MEASUREMENTS: Clamp-measured IS, age, BMI, and total
      testosterone. RESULTS: The prevalence of IR and reduction in IS were 56.3% and
      30.3%, respectively, in Chinese Han women with PCOS (both P < 0.001). The
      inherent reduction in IS was 18.8% in lean women with PCOS and BMI independently
      reduced IS by 37.9% in obese women with PCOS. The prevalence of IR estimated by
      homeostatic model assessment (HOMA) was lower than that determined by clamp. The
      multivariable analysis showed that IR by clamp (R2  = 0.48, P < 0.001) was
      independently associated with BMI (beta = -0.52, P < 0.001), waist-hip ratio
      (beta = -0.23, P < 0.001), total testosterone (beta = -0.07, P = 0.045) and age
      (beta = 0.17, P < 0.001), while IR by HOMA was only associated with BMI (R2  =
      0.25, beta = 0.50, P < 0.001). There were no differences in BMI groups
      distribution, HOMA-IR and M values among the four PCOS subtypes (all P > 0.05).
      CONCLUSIONS: 56.3% of Chinese Han women with PCOS had IR and their reduction in
      IS was 30.3%. Obesity exacerbated the reduction in IS. When being evaluated by
      HOMA, the prevalence and the risk factors of IR in Chinese women with PCOS were
      underestimated.

PMID- 30229991
TI  - Is APOE epsilon4 required for Alzheimer's disease to develop in TREM2 p.R47H
      variant carriers?

PMID- 30229992
TI  - The relationship between clinical and biochemical characteristics and quality of
      life in patients with polycystic ovary syndrome.
AB  - BACKGROUND AND OBJECTIVE: While has been well demonstrated that clinical
      characteristics of polycystic ovary syndrome (PCOS) are associated with an
      impaired quality of life (QoL) in patients, it is unclear that whether the
      biochemical aspects of PCOS can influence their QoL. We aimed to investigate the
      relationship between clinical and biochemical characteristics, and various
      domains of QoL in patients with PCOS. DESIGN: A cross-sectional study. PATIENTS
      AND MEASUREMENTS: We assessed the association between clinical and biochemical
      characteristics and QoL domains (psychosocial-emotional, fertility, sexual
      function, and obesity-menstrual) in a total of 211 women with PCOS using a
      specific health-related quality-of-life questionnaire for PCOS patients. RESULTS:
      Our findings showed positive significant association of QoL with age, and its
      negative significant associations with BMI, hirsutism and infertility (P < 0.05).
      We also found a negative association between FAI and total QoL (r = -0.14; P =
      0.042) and domains of hirsutism (r = -0.14; P = 0.045) and obesity-menstrual (r =
      -0.23; P = 0.001). DHEAS was positively associated with the sexual function
      aspect of QoL (r = 0.20; P = 0.043). There were no significant associations
      between QoL and other hormonal parameters including LH to FSH ratio and total
      testosterone (tT). Significant associations were found between triglycerides
      (TG), total cholesterol (TC), LDL and HDL cholesterol, and domain of obesity
      menstrual of QoL. HOMA-IR was significantly related to all QoL domains except
      self-image and hirsutism. CONCLUSION: Although biochemical markers can influence
      QoL in patients with PCOS, clinical manifestations of this syndrome such as
      obesity, infertility and hirsutism seem to play roles in worsening QoL, in
      particular for psychosocial domains. Hence, clinicians should regularly assess
      the clinical and psychosocial dimensions of PCOS as well as biochemical aspects.

PMID- 30229993
TI  - Safety of bivalent human papillomavirus vaccine in the US vaccine adverse event
      reporting system (VAERS), 2009-2017.
AB  - AIMS: Human papillomavirus (HPV) vaccines prevent infection with oncogenic virus
      types. We analysed reports to the US Vaccine Adverse Event Reporting System
      (VAERS) of adverse events (AE) following bivalent HPV vaccine (2vHPV). METHODS:
      We conducted descriptive analysis of 2vHPV reports, reviewed individual reports,
      calculated crude AE reporting rates and conducted empirical Bayesian data mining.
      RESULTS: Of 241 2vHPV reports, 158 were in females, 64 in males (2vHPV is
      approved for females only) and 19 with unknown sex; 95.8% were classified as
      nonserious. Dizziness, headache, nausea and injection site reactions were the
      most common symptoms. Crude AE reporting rates were 33.3 reports per 100 000
      doses distributed overall, and 1.4 per 100 000 for serious reports. Empirical
      Bayesian data mining identified disproportional reporting for three types of
      medical errors; assessment indicated findings that were probably driven by
      inadvertent 2vHPV use in males. CONCLUSIONS: We did not identify any new or
      unexpected safety concerns in our review of 2vHPV reports to VAERS.

PMID- 30229994
TI  - Per- and polyfluoroalkyl substances in Northern California cats: Temporal
      comparison and a possible link to cat hyperthyroidism.
AB  - The indoor environment and dietary intake are considered to be major human
      exposure pathways to per- and polyfluoroalkyl substances (PFASs). Cats have
      similar exposures to humans by sharing their residential environments, although
      they have different diet, body sizes, and indoor activities. In the present
      study, we report PFAS levels in the serum of 2 groups of Northern California cats
      (>10 yr old) collected during 2 time periods: 2008 to 2010 (n = 21) and 2012 to
      2013 (n = 22). Levels of ?PFAS (geometric mean) were lower in the second period
      (geometric mean = 8.10 ng/mL) than the first time period (geometric mean = 15.8
      ng/mL), although PFAS profiles remained similar. We also analyzed PFAS levels in
      human serum collected in the same time period (2008-2010) and geographic area,
      and compared the profiles and ?PFAS levels (15.8 vs 14.3 ng/mL for cat and human,
      respectively). Long chain perfluorinated carboxylic acids, especially
      perfluorononanoic acid and perfluoroundecanoic acid, were significantly higher in
      cat serum than in humans. Furthermore, serum from hyperthyroid cats in the second
      time period showed higher ?PFAS level (9.50 ng/mL) compared to nonhyperthyroid
      cats (7.24 ng/mL), and it is the perfluorooctanoic acid levels that were
      statistically significantly higher in hyperthyroid cats' serum (p < 0.05). This
      result may indicate a possible link between PFAS levels and cat hyperthyroid,
      warranting a larger study for further investigation. Environ Toxicol Chem
      2018;37:2523-2529. (c) 2018 SETAC.

PMID- 30229995
TI  - A rare cause of unilateral facial rash.

PMID- 30229996
TI  - Ultrastructure of vegetative cells and resting cysts, and live observations of
      the encystation and excystation processes in Diophrys oligothrix Borror, 1965
      (Protista, Ciliophora).
AB  - Ciliated protists can form cysts to resist unfavorable environmental conditions
      and then excyst when environmental conditions become favorable. This study used
      electron and light microscopy to investigate the structure of vegetative cells
      and resting cysts, as well as the encysting and excysting processes of Diophrys
      oligothrix. For the first time, ampules were revealed beneath the pellicle in the
      genus Diophrys, and their extrusome types differed between Diophrys species.
      Membrane-packed discs of diverse shapes were found in the cytoplasm just beneath
      the pellicle around the cytopharynx and were separated by rows of microtubule
      units. Beneath the discs, some double-layer microtubule structures were detected
      as well. During encystment, the ventral ciliature was folded in a ventral cavity
      of the cell, and the caudal cirri were retracted directly into the cyst in a
      separate cavity on the dorsal side. In the resting cysts, high autophagic
      activity occurred, possibly including digestion of membrane-packed discs and
      ampules. Two macronuclear nodules kept their basic shape, although the chromatin
      aggregation and fusion region were observed in ultrathin sections. The cyst wall
      contained two layers, namely, the ectocyst, and endocyst. In mature cysts, basal
      bodies and ciliary shafts were observed, demonstrating that D. oligothrix forms
      non-kinetosome-resorbing cysts. The process of excystment occurred in two modes,
      either with or without participation of a contractile vacuole.

PMID- 30229997
TI  - Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by
      inhibiting PI3K/AKT/mTOR and Ras/Raf pathways.
AB  - Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been
      reported for its antitumor activity on several cancers. However, its effect on
      human esophageal cancer remains unclear. In this study, we demonstrated that
      oridonin could inhibit the growth of human esophageal cancer cells both in vitro
      and in vivo. Oridonin not only suppressed the proliferation, but also induced
      cell cycle arrest and mitochondrial-mediated apoptosis in KYSE-30, KYSE-150, and
      EC9706 cells with dose-dependent manner. Further mechanism studies revealed that
      oridonin led cell cycle arrest in esophageal cancer cells via downregulating cell
      cycle-related proteins, such as cyclin B1 and CDK2, while upregulating p53 and
      p21. Oridonin also increased proapoptotic protein Bax and reduced antiapoptotic
      protein Bcl-2, as well as the increased expression of cleaved caspase-3, -8, and 
      9. In addition, oridonin treatment could significantly inhibit the PI3K/Akt/mTOR
      and Ras/Raf signaling pathway. In vivo results further demonstrated that oridonin
      treatment markedly inhibited tumor growth in the esophageal cancer xenograft mice
      model. Taken together, these results suggest that oridonin may be a potential
      anticancer agent for the treatment of esophageal cancer.

PMID- 30230000
TI  - Bernard Goldstein: Building Risk Analysis Institutions.

PMID- 30229998
TI  - Napping on night-shifts among nursing staff: A mixed-methods systematic review.
AB  - AIMS: To synthesize research on the influence of night-shift napping on nurses.
      BACKGROUND: Shift work is common for hospital nurses. Various studies corroborate
      that shift work causes adverse health consequences for nurses. Night-shift
      napping is a countermeasure to address the adverse outcomes of shift work.
      DESIGN: A mixed-methods systematic review. DATA SOURCES: The literature search
      included the PubMed, Web of Science, Embase, PsycINFO and Cochrane Library
      electronic databases from inception to December 2017. Reference lists were hand
      searched. Only English articles were chosen. REVIEW METHODS: A sequential
      explanatory design and Cochrane's methods for integrating qualitative and
      implementation evidence in intervention effectiveness reviews. The Mixed Methods
      Assessment Tool and Cochrane Risk of Bias Tool were applied to assess the
      methodological quality of included studies. RESULTS: Twenty-two studies met our
      inclusion criteria. Many nurses experienced napping during their night-shift
      although no clear policy emerged. Napping is beneficial to the well-being of
      nurses and could improve their psychomotor vigilance and performance. However,
      the related studies are limited. The evidence on reducing sleepiness and fatigue
      was also insufficient and napping in nursing still faces challenges. CONCLUSION:
      Although research on this topic has just started, napping during night-shift is
      beneficial to nurses' health and performance. Research should further explore the
      long-term impact on of night-shift napping on nurses, people and organization
      using sound methodological designs. Managers should actively develop strategies
      to address night-shift napping barriers.

PMID- 30229999
TI  - Evaluation of vitamin D status and its correlation with gonadal function in
      children at mini-puberty.
AB  - CONTEXT: The effects of Vitamin D on reproductive function in adults have gained
      interest. Studies have demonstrated some associations. Hypothalamic-pituitary
      gonadal axis is activated during the first 6 months of life, called as mini
      puberty. This HPG activation is important for future gonadal function. There are
      no data regarding the association of gonadal hormones and 25(OH)D levels at mini
      puberty. Demonstration of any association would form the basis for studies that
      will search for the effects of 25(OH)D on gonadal hormones at mini-puberty.
      OBJECTIVE: To characterize the associations between 25(OH)D levels and gonadal
      hormones at mini-puberty. DESIGN: Cross-sectional cohort analysis. PATIENT(S) OR
      OTHER PARTICIPANT(S): A total of 180 (94 boys and 86 girls) healthy appropriate
      for-gestational-age neonates were included. MAIN OUTCOME MEASURE(S): 25(OH)D, LH,
      FSH, total testosterone, oestradiol, AMH and inhibin B levels were measured at
      postnatal 30-45 days. All infants were divided into three groups including
      vitamin D deficiency (<10 ng/mL), vitamin D insufficiency (10-20 ng/mL) and
      vitamin D sufficiency (>20 ng/mL). Correlations between vitamin D status and
      reproductive hormones were analysed. RESULT(S): Total testosterone level was
      higher (mean: 0.52 +/- 0.32 vs 0.26 +/- 0.2 ng/mL; P: 0.008) and inhibin B was
      lower in 25(OH)D deficient than sufficient girls (mean: 21.2 +/- 15.71 vs 53.25
      +/- 47.25 pg/mL; P: 0.021). CONCLUSION(S): A modest effect of 25(OH)D was
      identified on total testosterone and inhibin B in girls at mini-puberty. The
      25(OH)D may have an effect on gonadal function during early life. Randomized
      controlled trials could clarify the importance of vitamin D on gonadal hormones
      at mini-puberty.

PMID- 30230001
TI  - From the Editors.

PMID- 30230002
TI  - Moderating effect of occupational stress on spirituality and depression of
      Registered Nurses in tertiary hospital: A structural equation model.
AB  - AIM: The aim of this study was to determine the influence of spirituality to
      depression and to determine the moderating effect of occupational stress among
      Registered Nurses. BACKGROUND: Depression is a major contributor to the global
      burden of disease and it is influenced by several factors. Spirituality can be a
      protective factor against depression. However, it remains underexplored among
      nurses who experience several precipitating factors of depression, including
      occupational stress. DESIGN: Cross-sectional, predictive-correlational study.
      METHODS: From August - December 2017, 242 purposively selected nurses from
      selected tertiary hospitals completed a four-part survey packet composed of the
      "robotfoto," Spirituality Assessment Scale, Expanded Nursing Stress Scale, and
      Beck's Depression Inventory-II. Structural equation modelling analysed the
      influence of spirituality to depression, while multigroup analysis determined the
      moderating effect of occupational stress. RESULTS: "Personal faith, spiritual
      contentment, and religious practice" negatively influenced depression, generating
      a good model. Occupational stress significantly moderated the influence of
      spirituality to depression, with a significant inverse U-shaped effect for both
      "personal faith" and "religious practice" and a non-significant decreasing effect
      for "spiritual contentment". CONCLUSION: The stress-moderated model of the
      influence of spirituality to depression highlights three significant points.
      First, there is a need to develop individualized, spiritually based interventions
      based on the spiritual needs of Registered Nurses. Second, policies geared
      towards positive spirituality in the workplace and spiritual support to nurses
      must be explored. Finally, nurse managers must identify the sources of
      occupational stress and implement stress-reducing programmes in the workplace.

PMID- 30230003
TI  - "Nurses' use of visual management in hospitals-A longitudinal, quantitative study
      on its implications on systems performance and working conditions".
AB  - AIM: The aim of this study was to examine potential benefits provided by daily
      visual management tool use and explore its association with systems performance
      and working conditions among hospital nurses. BACKGROUND: Visual management tools
      used in everyday work and improvement work in health care theoretically
      contribute to shared understanding of complex work systems and provide certain
      user benefits. Cognitive load, miscommunication within and between professional
      groups, and pressure to engage in care process redesign add to nurses' strained
      working conditions. DESIGN: Quantitative longitudinal. METHODS: Questionnaires
      were distributed at T0, (N = 948, 66% response rate), T1 (N = 900, 70% response
      rate), and T2 (N = 621, 72% response rate) to nurses at five hospitals. Three
      groups of users (daily users, start users, and non-daily users) were compared by
      means T1-T2 (significance tested with Wilcoxon signed rank test) and by mixed
      model repeated measures T0, T1, T2. RESULTS: Daily use associated to better
      overview of work, collaboration, social capital, and clinical engagement. Job
      resources were rated higher by daily users. Mental stress increased and
      development opportunities decreased over time among non-daily users. There were
      associations between use and perceptions of systems performance, though the
      differences between groups were small. CONCLUSION: This study specifically
      explores visual management tool use in the hospital setting, which contributes to
      research by broadening the understanding of cognitive, social, and emotional
      benefits provided by visual management tool use. Daily use was associated to
      positive working conditions, small but positive differences in systems
      performance, and indicated a buffering effect on nurses' mental stress.

PMID- 30230004
TI  - Multiple rapidly growing necrotic eruptions on the face.

PMID- 30230005
TI  - Comparable functional motor outcomes after repair of peripheral nerve injury with
      an elastase-processed allograft in a rat sciatic nerve model.
AB  - BACKGROUND: A bridging nerve autograft is the gold standard for the repair of
      segmental nerve injury that cannot be repaired directly. However, limited
      availability and donor site morbidity remain major disadvantages of autografts.
      Here, a nerve allograft decellularized with elastase was compared with an
      autograft regarding functional motor outcome in a rat sciatic segmental nerve
      defect model. Furthermore, the effect of storage on this allograft was studied.
      METHODS: Sixty-six Lewis rats (250-300 g) underwent a 10-mm sciatic nerve
      reconstruction using either a cold- (n = 22) or frozen-stored (n = 22)
      decellularized nerve allograft or an autograft (n = 22). Sprague-Dawley rats (300
      350 g) served as full major histocompatibility complex-mismatched donors.
      Functional motor outcome was evaluated after 12 and 16 weeks. Ankle angle,
      compound muscle action potential (CMAP), isometric tetanic force, wet muscle
      weight, and histomorphometry were tested bilaterally. RESULTS: For CMAP and
      isometric tetanic force, no significant differences were observed between groups.
      In contrast, for ankle angle, histomorphometry and muscle weight, the cold-stored
      allograft performed comparable to the autograft, while the frozen-stored
      allograft performed significantly inferior to the autograft. At week 16, ankle
      angle was 88.0 +/- 3.1% in the cold-stored group, 77.4 +/- 3.6% in the frozen
      stored group, and 74.1 +/- 3.1% in the autograft group (P < .001); At week 16,
      the muscle weight showed a recovery up to 71.1 +/- 4.8% in the autograft group,
      67.0 +/- 6.6% in the cold-stored group, and 64.7 +/- 3.7% in the frozen-stored
      group (P < .05). CONCLUSIONS: A nerve allograft decellularized with elastase, if
      stored under the right conditions, results in comparable functional motor
      outcomes as the gold standard, the autograft.

PMID- 30230007
TI  - Shutter-speed dynamic contrast-enhanced MRI: Is it fit for purpose?
AB  - PURPOSE: To test the ability of shutter-speed dynamic contrast-enhanced (DCE) MRI
      to estimate water exchange (WX) using simulations and assess its performance in
      clinical case studies of malignant and benign breast tumors. METHODS: Data were
      simulated using a 1-compartment tracer kinetic (TK) model combined with a 2-pool
      WX model (2PX) and with a 2-compartment TK model. Typical DCE-MRI acquisition
      parameters were used with both WX-sensitive (8 degrees ) and -insensitive (25
      degrees ) flip angles. Clinical data were obtained from patients with malignant
      and benign breast tumors. Data were fitted using a 2-compartment TK model and a 1
      compartment TK model combined with 4 WX models: fast exchange limit (FXL), no
      exchange, 2PX, and shutter-speed. RESULTS: Fits to the 1-compartment simulated
      data were excellent, but estimates of WX obtained using the 2PX and shutter-speed
      models were poor. One-compartment TK model fits to the clinical malignant tumor
      data were bad, except for the shutter-speed model. However, that overestimated TK
      parameters compared to the best-fit 2-compartment TK model, which predicted a
      significant blood volume and leaky capillaries (1 tracer compartment is
      insufficient, 2 are necessary). All models produced excellent fits to the
      clinical benign tumor data with little variation between parameter estimates (1
      tracer compartment is sufficient). CONCLUSION: The 2PX and shutter-speed models
      were unable to estimate WX from the DCE-MRI data. A good fit to malignant tumor
      data using the shutter-speed model was not explained by WX, but the choice of an
      inappropriate TK model leading to distorted parameter estimates.

PMID- 30230008
TI  - Editorial.

PMID- 30230006
TI  - High muscle co-contraction does not result in high joint forces during gait in
      anterior cruciate ligament deficient knees.
AB  - The mechanism of knee osteoarthritis development after anterior cruciate ligament
      injuries is poorly understood. The objective of this study was to evaluate knee
      gait variables, muscle co-contraction indices and knee joint loading in young
      subjects with anterior cruciate ligament deficiency (ACLD, n = 36), versus
      control subjects (n = 12). A validated, electromyography-informed model was used
      to estimate joint loading. For the involved limb of ACLD subjects versus control,
      muscle co-contraction indices were higher for the medial (p = 0.018, effect size
      = 0.93) and lateral (p = 0.028, effect size = 0.83) agonist-antagonist muscle
      pairs. Despite higher muscle co-contraction, medial compartment contact force was
      lower for the involved limb, compared to both the uninvolved limb (mean
      difference = 0.39 body weight, p = 0.009, effect size = 0.70) as well as the
      control limb (mean difference = 0.57 body weight, p = 0.007, effect size = 1.14).
      Similar observations were made for total contact force. For involved versus
      uninvolved limb, the ACLD group demonstrated lower vertical ground reaction force
      (mean difference = 0.08 body weight, p = 0.010, effect size = 0.70) and knee
      flexion moment (mean difference = 1.32% body weight * height, p = 0.003, effect
      size = 0.76), during weight acceptance. These results indicate that high muscle
      co-contraction does not always result in high knee joint loading, which is
      thought to be associated with knee osteoarthritis. Long-term follow-up is
      required to evaluate how gait alterations progress in non-osteoarthritic versus
      osteoarthritic subjects. (c) 2018 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res.

PMID- 30230009
TI  - TensorView: A software tool for displaying NMR tensors.
AB  - The representation of nuclear magnetic resonance (NMR) tensors as surfaces on
      three-dimensional molecular models is an information-rich presentation that
      highlights the geometric relationship between tensor principal components and the
      underlying molecular and electronic structure. Here, we describe a new
      computational tool, TensorView, for depicting NMR tensors on the molecular
      framework. This package makes use of the graphical interface and built-in
      molecular display functionality present within the Mathematica programming
      environment and is robust for displaying tensor properties from a broad range of
      commercial and user-specific computational chemistry packages. Two mathematical
      forms for representing tensor interaction surfaces are presented, the popular
      ellipsoidal construct and the more technically correct "ovaloid" form. Examples
      are provided for chemical shielding and shift tensors, dipole-dipole and
      quadrupolar couplings, and atomic anisotropic displacement parameters (thermal
      ellipsoids) derived from NMR crystallography.

PMID- 30230010
TI  - The learning history: A research method to advance the science and practice of
      organizational learning in healthcare.
AB  - AIMS: This paper presents a discussion of the learning history research method,
      including a description of how to conduct a learning history. Suggested
      applications of the method in research and clinical practice are also provided.
      BACKGROUND: Organizational learning has been linked to improved clinical
      performance and other positive outcomes in healthcare. Yet, the theoretical
      guidance available to researchers and clinical leaders who study and strive to
      foster organizational learning is sparse. Studying how organizational learning
      occurs in the healthcare context is a critical step toward addressing this
      knowledge gap. The learning history, a participatory research method, is
      specifically designed for studying the organizational learning process. Thus, it
      is precisely suited for the work of developing a theoretical foundation for
      organizational learning in healthcare. DESIGN: Discussion paper. DATA SOURCES:
      This discussion paper is based on relevant literature and the authors'
      experiences conducting learning histories. IMPLICATIONS FOR NURSING: Researchers
      can use learning histories to develop a better understanding of and a theoretical
      foundation for organizational learning in healthcare. Leaders in clinical
      practice can use learning histories to foster learning and improvement in their
      organizations. CONCLUSION: Learning histories are a promising approach to
      advancing the science and practice of organizational learning.

PMID- 30230011
TI  - Compassion focused therapy for people with dementia: A feasibility study.
AB  - OBJECTIVES: There is a lack of evidence-based psychological therapies for
      dementia and psychological distress. The study aimed to develop a compassion
      focused therapy intervention for people with dementia with depression and/or
      anxiety, and to assess its feasibility, acceptability, and utility. METHODS: A
      mixed methods multiple case series (n = 7) was used to assess the intervention's
      feasibility and changes in self-compassion, mood, anxiety, and quality of life.
      Outcome measures were administered at pre-intervention, midpoint, and post
      intervention. Data were analysed using reliable change and clinically significant
      change. Thematic analysis on post-therapy interviews and session rating forms was
      used to assess acceptability and perceived change from the intervention. RESULTS:
      Over the course of the intervention, improvements in mood, anxiety, and self
      compassion were seen, and three of six participants moved out of the clinical
      depression range. Six participants were able to engage in soothing rhythm
      breathing, and five in discussion of self-criticism and developing self
      compassion. Several participants and their carers described increased self
      compassion in response to cognitive decline. CONCLUSIONS: Compassion focused
      therapy can be adapted to be delivered to people with dementia and low mood,
      anxiety, or other distress. The intervention may improve self-compassion, mood,
      and anxiety. A larger pilot trial with a comparator group and follow-up is needed
      to evaluate the intervention's effectiveness for people with dementia.

PMID- 30230012
TI  - Social jetlag and quality of life among nursing students: A cross-sectional
      study.
AB  - AIMS: To investigate chronotype categories and social jetlag among nursing
      students and to identify associations between rhythm asynchrony and participants'
      physical and psychological health, academic performance and quality of life.
      BACKGROUND: Social jetlag refers to the asynchrony between chronotypes and social
      working hours, resulting in a misalignment of biological and social time. Recent
      studies have reported possible changes in psychosocial functioning owing to
      social jetlag. Therefore, the present study investigated chronotypes and the
      extent of social jetlag among nursing students. DESIGN: A cross-sectional study
      was conducted in 2015 with a sample of 346 nursing students in two universities
      in Korea. METHODS: Social jetlag and quality of life were measured with the
      Munich Chronotype Questionnaire and the abbreviated version of the World Health
      Organization Quality of Life Scale, respectively, in the year 2015. Data analysis
      was mainly based on a multiple regression to identify social jetlag's influence
      on students' quality of life. RESULTS: Average social jetlag was 1 hour and 36
      minutes. Social jetlag was negatively correlated with chronotype, academic
      performance and quality of life. A multiple regression analysis revealed that
      social jetlag, a positive emotional state, recovery resilience and depressive
      symptoms affected students' quality of life. These variables accounted for 41.7%
      of the variance in quality of life. CONCLUSIONS: Results suggest that decreases
      in social jetlag and depressive symptoms, as well as increases in the positive
      emotional state and recovery resilience, enhance students' quality of life. This
      article is protected by copyright. All rights reserved.

PMID- 30230013
TI  - Role of full-thickness cartilage defects in knee osteoarthritis (OA) incidence
      and progression: Data from the OA Initiative.
AB  - The purpose of this study is to determine whether full-thickness tibiofemoral
      cartilage defects are predictive of incident radiographic OA, progression of
      radiographic OA, and progression to severe radiographic OA. Participants in the
      OA Initiative (n = 1317, 38.1% male, mean age 60.9 years SD 9.2) with baseline
      MRIs and Kellgren-Lawrence (KL) OA grade 0-3 (none to moderate OA) were included.
      All participants had follow-up radiographs at mean 4.9 years (max 8.0). The
      effect of full-thickness defect presence, size, and location on risk of incident
      OA (KL grade 2+), overall progression of OA (increase in KL grade 1+ points), or
      compartment-specific OA progression was assessed with Cox proportional hazards
      modeling with adjustment for demographic factors, weight, and knee alignment. The
      yearly incidence of tibiofemoral OA was 0.3% (CI 0.2-0.4%); defect presence,
      size, and location were not associated with incident OA risk. The yearly rate of
      OA progression was 3.8% in participants without tibiofemoral full-thickness
      defects, 6.7% with medial defects, and 6.3% with lateral defects. Medial bipolar
      (kissing) lesions were an independent risk factor for OA progression as well as
      medial compartment progression. Lateral tibial-sided full-thickness defects
      increased risk of lateral progression (increase in lateral OARSI grade). In older
      adults, isolated full-thickness cartilage defects do not increase short-term risk
      of incident OA. However, in the setting of preexisting mild or moderate OA,
      medial bipolar (kissing) defects increase risk of overall OA progression (KL
      grade) as well as progression of medial compartment OA. Lateral tibial defects
      increase risk of lateral compartment OA progression. (c) 2018 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 30230014
TI  - Symplectomorphic registration with phase space regularization by entropy spectrum
      pathways.
AB  - PURPOSE: The ability to register image data to a common coordinate system is a
      critical feature of virtually all imaging studies. However, in spite of the
      abundance of literature on the subject and the existence of several variants of
      registration algorithms, their practical utility remains problematic, as commonly
      acknowledged even by developers of these methods. METHODS: A new registration
      method is presented that utilizes a Hamiltonian formalism and constructs
      registration as a sequence of symplectomorphic maps in conjunction with a novel
      phase space regularization. For validation of the framework a panel of
      deformations expressed in analytical form is developed that includes deformations
      based on known physical processes in MRI and reproduces various distortions and
      artifacts typically present in images collected using these different MRI
      modalities. RESULTS: The method is demonstrated on the three different magnetic
      resonance imaging (MRI) modalities by mapping between high resolution anatomical
      (HRA) volumes, medium resolution diffusion weighted MRI (DW-MRI) and HRA volumes,
      and low resolution functional MRI (fMRI) and HRA volumes. CONCLUSIONS: The method
      has shown an excellent performance and the panel of deformations was instrumental
      to quantify its repeatability and reproducibility in comparison to several
      available alternative approaches.

PMID- 30230015
TI  - The mitigation effects of exogenous melatonin on replant disease in apple.
AB  - Melatonin mediates many physiological processes in plants. The problem of apple
      replant disease is unsolved. Our study objectives were to evaluate the regulatory
      effect of melatonin on plant resistance to this challenge and investigate the
      preliminary mechanism by which melatonin helps alleviate the effects of this
      disease. Two-year-old trees of "Fuji" apple (Malus domestica), grafted onto
      rootstock M.26, were grown in "replant" soil for 6 months in the absence or
      presence of a 200 MUmol/L melatonin supplement. The addition of melatonin to the
      soil significantly increased the rates of plant growth and net photosynthesis and
      chlorophyll concentrations under replant conditions. This molecule elevated the
      levels of K in leaves and roots and enhanced the activity of soil enzymes. Such
      supplementation also changed the composition of the bacterial and fungal
      communities in the soil. We concluded that the application of melatonin to a
      replant soil can protect their chloroplasts from oxidative damage and release the
      apple root from membrane damage, and also lead to increased soil enzyme activity
      and soil quality while altering the composition of bacterial and fungal
      communities. These changes can then promote seedling growth, stimulate
      photosynthesis, and elevate K levels, thereby alleviating the effects of apple
      replant disease.

PMID- 30230016
TI  - Targeted partial reconstruction for real-time fMRI with arbitrary trajectories.
AB  - PURPOSE: A partial image reconstruction formalism is introduced for the targeted
      extraction of real-time feedback from arbitrary trajectories when full image
      reconstruction in real time is computationally too demanding. METHODS: Explicit
      calculation and storage of linear combinations of lines of the reconstruction
      matrix by an incomplete basis change in spatial coordinates lead to translation
      of the expensive full reconstruction from a frame-wise application to a region of
      interest (ROI)-wise application. This step is independent from signal data and
      can be executed before the experiment. Subsequently, the results of the sum over
      fully reconstructed voxels can be evaluated directly. Data from a high-speed fMRI
      acquisition was used to investigate the targeted partial reconstruction of a
      functional ROI atlas, incorporating an intravolume dephasing correction. The same
      data and ROIs were used for a comparison of the time series obtained with those
      obtained from already existing methods for compartment-wise reconstruction. To
      examine real-time feasibility, the reconstruction was implemented and tested for
      online reconstruction performance. RESULTS: The reconstruction yields results
      that are virtually identical to the standard reconstruction (i.e., the magnitude
      sums over the ROIs), with negligible discrepancies even after termination of the
      conjugate gradient algorithm at a feasible number of iterations. Notably, more
      discrepancies arise with existing compartment-wise reconstructions. The online
      real-time implementation evaluated 1 ROI within 2.8 ms in the case of a highly
      parallel 3D whole brain acquisition. CONCLUSION: The high reconstruction fidelity
      and speed are satisfying for the exemplary application of real-time functional
      feedback using a highly parallel 3D whole brain acquisition.

PMID- 30230017
TI  - Economic burden, impoverishment, and coping mechanisms associated with out-of
      pocket health expenditure in India: A disaggregated analysis at the state level.
AB  - INTRODUCTION: The high share of out-of-pocket (OOP) health expenditure imposes an
      extreme financial burden on households, and they have to incur a substantial
      amount of expenditure to avail health care services. This study analyses the
      inter-state differentials in the economic burden of OOP health expenditure,
      resultant impoverishment impact, and sources of finance used as coping
      mechanisms. MATERIALS AND METHODS: The study is based on health expenditure
      survey, namely the 71st Round on "Key Indicators of Social Consumption in India:
      Health," (2014) conducted in India by the National Sample Survey Organisation.
      The study uses headcount, payment gap, and concentration index to measure the
      economic burden, impoverishment impact of OOP health expenditure, and the level
      of inequality. RESULTS: On the basis of results, the states can be divided into
      four distinct categories: (1) States with low economic burden and low poverty
      impact of OOP health expenditure, (2) low economic burden and high poverty impact
      of OOP health expenditure, (3) high economic burden and low poverty impact of OOP
      health expenditure, and (4) high economic burden and high poverty impact of OOP
      health expenditure. CONCLUSIONS: Inter-state differentials in OOP health
      expenditure and impoverishment need proper attention of the government especially
      the policy makers.

PMID- 30230018
TI  - Resilience in family caregiving for people with dementia: A systematic review.
AB  - OBJECTIVE: The objective of this review is to critically examine, evaluate, and
      synthesize the literature on resilience in family caregiving for people with
      dementia. METHODS: A systematic literature review was conducted according to
      PRISMA guidelines to identify articles which examined resilience and related
      concepts in family caregiving for people with dementia. The review was based on a
      systematic search of scholarly databases, to yield peer-reviewed articles and
      grey literature, published between 2006 and 2016. Two independent reviewers
      prescreened the search results and conducted formal assessments and quality
      appraisals of the retrieved articles. RESULTS: A total of 13 863 articles were
      identified by the systematic search, and 52 articles were included in the review.
      Based on a critical narrative synthesis of the literature, the study proposes a
      model of resilience for family carers of people with dementia, which incorporates
      the context of caring, social and cultural characteristics, and psychological
      dimensions of caring. CONCLUSIONS: The results indicate that there is no single
      approach to enhancing resilience among family carers of people with dementia.
      Resilience is a multifaceted response to the caregiving role, and is influenced
      by a multitude of interrelated factors. However, the factors and resources
      outlined have been addressed, with limited success in some cases, by psychosocial
      interventions in the field. While the work conducted to date to develop
      resilience-enhancing interventions has been marked with some success, the next
      wave of carer research could usefully examine ecological perspectives on carer
      outcomes, including carer resilience.

PMID- 30230019
TI  - Cognitive functioning and structural brain abnormalities in people with Type 2
      diabetes mellitus.
AB  - AIMS: Type 2 diabetes mellitus is associated with cognitive dysfunction, but the
      underlying structural brain correlates are uncertain. This study examined the
      association between cognitive functioning and structural brain abnormalities in
      people with long-standing Type 2 diabetes. METHODS: Ninety-three people with Type
      2 diabetes (age 62.3 +/- 5.4 years, diabetes duration 9.7 +/- 6.7 years; HbA1c 65
      +/- 10 mmol/mol, 8.1 +/- 1.3%) were included. Cognitive functioning was assessed
      by a test battery covering the domains memory, processing speed and executive
      functioning. Brain tissue volumes and white matter hyperintensity volumes were
      automatically determined on MRI. Linear regression analyses were performed
      adjusted for age, sex and education. RESULTS: In people with Type 2 diabetes,
      increased white matter hyperintensity volume was associated with decreased
      processing speed [regression B coefficient = -0.22 (-0.38 to -0.06), P = 0.009],
      but not with memory or executive function (P > 0.05). Brain tissue volumes were
      not significantly related to cognitive functioning (P > 0.05). CONCLUSIONS: In
      people with long-standing, less strictly controlled Type 2 diabetes, white matter
      hyperintensities volumes were associated with decreased processing speed. This
      suggests that cerebral small vessel disease is an underlying disease mechanism of
      cognitive dysfunction in these individuals.

PMID- 30230020
TI  - Does tight glycaemic control with insulin therapy in the early neonatal period
      improve long-term outcomes?

PMID- 30230022
TI  - Efferocytosis: molecular mechanisms and pathophysiological perspectives.
AB  - During the life of a human being, several tons of apoptotic cells and debris are
      produced. These apoptotic particles should be cleared quickly and accurately from
      the body, as they may lose their membrane integrity with the probability of
      leakage of cytotoxic materials and other intracellular antigens into the
      environment. The action of removing apoptotic particles occurs by a process
      called efferocytosis. Efferocytosis is a highly regulated balance among a set of
      find-me, eat-me and don't-eat-me signals. Efferocytosis is accompanied by a
      suppression of the immune system that can explain its negative role in cancer.
      Additionally, defects in this process can lead to different diseases. In this
      review, we aim to describe the mechanism of efferocytosis and evaluate its
      association with the development of autoimmune diseases, airway inflammation,
      atherosclerosis and cancer to open a new window for the treatment of these
      diseases.

PMID- 30230021
TI  - Semi-automated generation of individual computational models of the human head
      and torso from MR images.
AB  - PURPOSE: Simulating the interaction of the human body with electromagnetic fields
      is an active field of research. Individualized models are increasingly being
      used, as anatomical differences affect the simulation results. We introduce a
      processing pipeline for creating individual surface-based models of the human
      head and torso for application in simulation software based on unstructured
      grids. The pipeline is designed for easy applicability and is publicly released
      on figshare. METHODS: The pipeline covers image acquisition, segmentation,
      generation of segmentation masks, and surface mesh generation of the single,
      external boundary of each structure of interest. Two gradient-echo sequences are
      used for image acquisition. Structures of the head and body are segmented using
      several atlas-based approaches. They consist of bone/skull, subarachnoid
      cerebrospinal fluid, gray matter, white matter, spinal cord, lungs, the sinuses
      of the skull, and a combined class of all other structures including skin. After
      minor manual preparation, segmentation images are processed to segmentation
      masks, which are binarized images per segmented structure free of misclassified
      voxels and without an internal boundary. The proposed workflow is applied to 2
      healthy subjects. RESULTS: Individual differences of the subjects are well
      represented. The models are proven to be suitable for simulation of the RF
      electromagnetic field distribution. CONCLUSION: Image segmentation, creation of
      segmentation masks, and surface mesh generation are highly automated. Manual
      interventions remain for preparing the segmentation images prior to segmentation
      mask generation. The generated surfaces exhibit a single boundary per structure
      and are suitable inputs for simulation software.

PMID- 30230023
TI  - Does abuse in late life worsen sleep quality? A two-year prospective cohort study
      among rural older adults.
AB  - BACKGROUND: Elder abuse and neglect (EAN) is a growing public health problem, and
      numerous adverse health effects of abuse in late life have been documented.
      Little is known, however, about the impact of elder abuse on sleep quality. This
      study examines the longitudinal relationship between EAN and sleep quality.
      METHODS: This was a 2-year prospective cohort study involving 1927 older adults
      in a rural Malaysian district, Kuala Pilah. A multi-stage cluster sampling
      strategy was employed. After 2 years, 1189 respondents were re-assessed. EAN was
      determined using the modified Conflict Tactic Scale, while sleep quality was
      measured using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The prevalence
      of elder abuse was 8.1% (95% CI:6.9,9.3). Longitudinal analysis using generalized
      estimating equations showed that elder abuse contributed to higher PSQI scores
      (B:0.49, 95% CI:0.17,0.58). Sub-analyses demonstrated that psychological abuse
      and neglect had significant longitudinal relationships with increase of PSQI
      scores, while other subtypes did not. CONCLUSION: Abuse in late life,
      particularly psychological abuse and neglect, result in greater PSQI scores. Even
      though this may imply decline in sleep quality, our findings were not considered
      clinically significant as they did not exceed the clinical cut-off score of five.
      Nevertheless, sleep quality is an important determinant of health and a predictor
      of mortality among older adults; thus, understanding its relationship with abuse
      is useful to health care providers and policy-makers in improving health services
      and upgrading preventive measures.

PMID- 30230024
TI  - Unusual skin manifestations associated with parvovirus B19 primary infection in
      children.
AB  - Parvovirus B19 is a DNA virus of the Parvoviridae family. We present four
      children with unusual exanthems associated with parvovirus infection: a purpuric
      periflexural pattern, a purpuric vasculitic pattern, and a combination of the
      two.

PMID- 30230026
TI  - Four-year outcome of randomly assigned lifestyle treatments in primary care of
      children with obesity.
AB  - AIM: To assess the four-year outcome in children with obesity randomised to one
      of two 12-month lifestyle treatment programmes in primary care. METHODS: At
      baseline, 64 children with obesity aged 8.0-13.0 years were randomised to a
      treatment programme managed either by a nurse, dietician and physiotherapist (n =
      32) or by a nurse and dietician (n = 32). RESULTS: From baseline to follow-up,
      the mean body mass standard deviation score (BMISDS) had decreased by -0.50
      [standard deviation (SD) 0.73], p = 0.002, in the nurse, dietician and
      physiotherapist group (n = 27), by -0.26 (SD 0.73), p = 0.057 in the other group
      (n = 29); adjusted mean difference was -0.22, 95% confidence interval -0.59;
      0.16, p = 0.25. Changes in weight categories did not differ between the groups:
      both had a change from obesity to normal weight in 1 and to overweight in 6; in
      the physiotherapist group 1 case of severe obesity changed to obesity. The
      combined treatment groups (n = 56) had a mean reduction in BMISDS of -0.37 (SD
      0.73) and an improved distribution in weight categories, p = 0.015. CONCLUSION:
      After four years, there was no difference in outcome between the treatment
      options. In the treatment groups combined the number of children with obesity and
      their adiposity measures were significantly lower.

PMID- 30230025
TI  - Long-term insulin treatment leads to a change in myosin heavy chain fiber
      distribution in OLETF rat skeletal muscle.
AB  - The objective of this study was to investigate molecular and physiological
      changes in response to long-term insulin glargine treatment in the skeletal
      muscle of OLETF rats. Male Otsuka Long-Evans Tokushima Fatty (OLETF) and Long
      Evans Tokushima Otsuka (LETO) rats aged 24 weeks were randomly allocated to
      either treatment with insulin for 24 weeks or no treatment, resulting in three
      groups. Insulin glargine treatment in OLETF rats (OLETF-G) for 24 weeks resulted
      in changes in blood glucose levels in intraperitoneal glucose tolerance tests
      compared with age-matched, untreated OLETF rats (OLETF-C), and the area under the
      curve was significantly decreased for OLETF-G rats compared with OLETF-C rats (P
      < 0.05). The protein levels of MHC isoforms were altered in gastrocnemius muscle
      of OLETF rats, and the proportions of myosin heavy chain type I and II fibers
      were lower and higher, respectively, in OLETF-G compared with OLETF-C rats.
      Activation of myokines (IL-6, IL-15, FNDC5, and myostatin) in gastrocnemius
      muscle was significantly inhibited in OLETF-G compared with OLETF-C rats ( P <
      0.05). MyoD and myogenin levels were decreased, while IGF-I and GLUT4 levels were
      increased, in the skeletal muscle of OLETF-G rats ( P < 0.05). Insulin glargine
      treatment significantly increased the phosphorylation levels of AMPK, SIRT1, and
      PGC-1alpha. Together, our results suggested that changes in the distribution of
      fiber types by insulin glargine could result in downregulation of myokines and
      muscle regulatory proteins. The effects were likely associated with activation of
      the AMPK/SIRT1/PGC-1alpha signaling pathway. Changes in these proteins may at
      least partly explain the effect of insulin in skeletal muscle of diabetes
      mellitus.

PMID- 30230027
TI  - Remission of proteinuria in multidrug-resistant idiopathic nephrotic syndrome
      following immunoglobulin immunoadsorption.
AB  - AIM: Complete or partial resistance to prednisone and calcineurin inhibitors in
      children with idiopathic nephrotic syndrome often leads to end-stage renal
      disease. The aim of the study was to report the outcome of patients with
      multidrug-resistant nephrotic syndrome treated with an association of
      immunoglobulin immunoadsorption, intravenous immunoglobulins and B-cell
      depletion. METHODS: At treatment initiation, patients received ten sessions of
      immunoglobulin immunoadsorption and intravenous immunoglobulins in two weeks
      followed by one rituximab in case of remission. RESULTS: A remission of
      proteinuria was obtained in nine out of 14 patients at the end of the initial
      phase and in two additional patients after an extended period. The remission was
      stable in three patients and after additional IgIA and heavy immunosuppression in
      six. Two patients that initially responded relapsed after IgIA withdrawal and
      remained with an uncontrolled disease at last follow-up. Three patients did not
      respond to the treatment including two who were found to have a genetic
      podocytopathy. CONCLUSION: Patients with multidrug-resistant idiopathic nephrotic
      syndrome can be successfully led into remission by IgIA prior to reaching end
      stage renal disease. However, IgIA does not suppress the need for heavy
      additional immunosuppression to control INS in most cases.

PMID- 30230029
TI  - Re: McKinney TB et al: Comparison of water and air charged transducer catheter
      pressures in the evaluation of cystometrogram and voiding pressure studies.
      Neurourol Urodyn 2018 DOI: 10.1002/nau23466.

PMID- 30230028
TI  - Comparative study of alpha- and beta-pinene effect on PTZ-induced convulsions in
      mice.
AB  - Convulsions occur in response to a loss of balance between excitatory and
      inhibitory neurotransmitters, and the treatment for this condition consists in
      restore such lost balance. Many anticonvulsant drugs present side effects which
      may limit their use. This fact has stimulated the search for new sources of
      treatment from aromatic plants. Many monoterpenes commonly present in essential
      oils are known because of their anticonvulsant properties. The anticonvulsant
      effect of alpha- and beta-pinene, two structural isomers, is still little
      studied. Thus, the present work evaluated the anticonvulsant effect of alpha- and
      beta-pinene in pentylenetetrazole-induced convulsions model. Initially, the oral
      LD50 for alpha- and beta-pinene was estimated. Following the oral administration,
      a mild sedation was observed and no deaths were recorded; the LD50 estimated for
      both monoterpenes was greater than 2 000 mg/kg, p.o. Further, animals were orally
      treated with alpha-pinene (100, 200 and 400 mg/kg), beta-pinene (100, 200 and 400
      mg/kg) and the equimolar mixture of alpha- and beta-pinene (400 mg/kg) and
      subjected to the pentylenetetrazole-induced convulsions model. In this model,
      only the dose of 400 mg/kg of the compounds was able to significantly decrease
      the seizure intensity. The latency of first convulsion was significantly
      increased by the mixture of alpha- and beta-pinene (400 mg/kg). In addition, beta
      pinene and the mixture of the two monoterpenes, both at a dose of 400 mg/kg,
      significantly increased the time of death of animals. The treatment with beta
      pinene and the equimolar mixture of the two monoterpenes significantly reduced
      hippocampal nitrite level and striatal content of dopamine (DA) and
      norepinephrine (NE). Taken together, the results suggest that alpha-pinene
      appears to be devoid of anticonvulsant action. This fact, however, seems to be
      dependent on the chemical structure of the compound, since pretreatment with the
      beta-pinene increased the time of death pf PTZ-treated mice, which seems to
      depend on the ability of the compound to reduce nitrite concentration and NE and
      DA content, during the pentylenetetrazole-induced seizure.

PMID- 30230030
TI  - Magnolin targeting of ERK1/2 inhibits cell proliferation and colony growth by
      induction of cellular senescence in ovarian cancer cells.
AB  - Ras/Raf/MEKs/ERKs and PI3 K/Akt/mTOR signaling pathways have key roles in cancer
      development and growth processes, as well as in cancer malignance and
      chemoresistance. In this study, we screened the therapeutic potential of magnolin
      using 15 human cancer cell lines and combined magnolin sensitivity with the CCLE
      mutaome analysis for relevant mutation information. The results showed that
      magnolin efficacy on cell proliferation inhibition were lower in TOV-112D ovarian
      cancer cells than that in SKOV3 cells by G1 and G2/M cell cycle phase
      accumulation. Notably, magnolin suppressed colony growth of TOV-112D cells in
      soft agar, whereas colony growth of SKOV3 cells in soft agar was not affected by
      magnolin treatment. Interestingly, phospho-protein profiles in the MAPK and PI3 K
      signaling pathways indicated that SKOV3 cells showed marked increase of Akt
      phosphorylation at Thr308 and Ser473 and very weak ERK1/2 phosphorylation levels
      by EGF stimulation. The phospho-protein profiles in TOV-112D cells were the
      opposite of those of SKOV3 cells. Importantly, magnolin treatment suppressed
      phosphorylation of RSKs in TOV-112D, but not in SKOV3 cells. Moreover, magnolin
      increased SA-beta-galactosidase-positive cells in a dose-dependent manner in TOV
      112D cells, but not in SKOV3 cells. Notably, oral administration of Shin-Yi
      fraction 1, which contained magnolin approximately 53%, suppressed TOV-112D cell
      growth in athymic nude mice by induction of p16Ink4a and p27Kip1 . Taken
      together, targeting of ERK1 and ERK2 is suitable for the treatment of ovarian
      cancer cells that do not harbor the constitutive active P13 K mutation and the
      loss-of-function mutations of the p16 and/or p53 tumor suppressor proteins.

PMID- 30230031
TI  - Genotoxicity and mutagenicity assessment of food contaminant mixtures present in
      the French diet.
AB  - Through diet, people are exposed simultaneously to a variety of contaminants
      (e.g. heavy metals, mycotoxins, pesticides) that could have combined adverse
      effects on human health. A previous study identified six main mixtures of food
      contaminants to which French adult consumers are exposed. These complex mixtures
      are comprised of 11 to 19 chemicals that have numerous toxic properties. In the
      present study, we investigated the genotoxic effects of these food contaminants,
      as single molecules and in mixtures that reflect their occurrence in the French
      diet, using the gammaH2AX assay in two human cell lines (HepG2, LS-174 T).
      Results of detailed analysis of the 49 individual contaminants (including 21
      tested in this study) demonstrated a positive genotoxic response to 14
      contaminants in HepG2 and 12 in LS-174 T cells. Next, our results indicated that
      two mixtures out of six triggered significant gammaH2AX induction after 24 hr of
      treatment, at concentrations for which individual compounds did not induce any
      DNA damage, suggesting more than additive interactions between chemicals.
      gammaH2AX positive mixtures were then tested for mutagenicity with the innovative
      in vitro PIG-A assay in HepG2 cells coupled with the soft agar colony formation
      assay. The two gammaH2AX positive mixtures led to a significant increase in the
      frequency of PIG-A GPI-deficient cells and in the number of colonies formed in
      soft agar. In conclusion, our study demonstrates that two mixtures of
      contaminants present in the French diet induce genotoxicity and mutagenicity, and
      that the combined effects of single molecules present in these mixtures are
      likely not additive, highlighting potential problems for hazard assessment of
      mixtures. Environ. Mol. Mutagen. 59:742-754, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 30230032
TI  - Long-term culture and in vitro maturation of macroencapsulated adult and neonatal
      porcine islets.
AB  - Encapsulated porcine islets could be used to treat type I diabetes without
      necessitating severe immunosuppression. Islet survival and secretory function in
      the encapsulation device need to be preserved to ensure efficient insulin output
      in response to surrounding stimuli. In the present study, we evaluated stimulated
      insulin secretion from adult and neonatal pig islets seeded on an acellular
      collagen matrix and encapsulated in alginate during long-term culture. Pig islets
      survived longer and secreted more insulin when cultured on acellular porcine
      dermis compared to human fascia. Islets from neonatal pigs could survive up to 33
      weeks in vitro, and their insulin secretion increased during the first 5 weeks of
      culture in a beta-cell maturation medium. In fact, by the 4th week of culture,
      insulin secretion from neonatal islets attained the same level as adult islets
      and even surpassed it by the 18th week. Our results show that in vitro maturation
      of encapsulated neonatal porcine islets is possible and can actually compensate
      the initial low insulin secretion from these islets while allowing enough time to
      perform complete functional and biosafety characterization of islets before
      transplantation.

PMID- 30230033
TI  - Amphiregulin enhances cell migration and resistance to doxorubicin in
      chondrosarcoma cells through the MAPK pathway.
AB  - Chondrosarcoma is characterized by the ability to produce extracellular matrix of
      cartilage. Curative surgical resection becomes difficult when high-grade
      chondrosarcoma metastasizes to other parts of the body. Doxorubicin (Dox) has
      been widely used clinically to treat many different types of cancers, including
      chondrosarcomas. However, chondrosarcoma is often resistant to chemotherapy and
      radiotherapy. New systemic treatment regimens are needed to improve the
      prognosis. Amphiregulin (AR) has been reported to be involved in cancer
      metastasis and drug resistance. The aim of the present study was to investigate
      the role of AR on cell migration and Dox sensitivity. To gain insight into the
      mechanisms used by AR to mediate its effects, we generated two chondrosarcoma
      cell lines, migration-prone JJ012 and Dox-resistant SW1353, to analyze the
      relationship between AR levels and cell functions. AR was highly expressed and
      secreted in mobile and drug-resistant cells. Next, we used the lentivirus
      mediated RNAi system to knock down AR expression and found that AR silencing was
      significantly attenuated in cell migration and drug resistance. In addition, we
      used exogenous recombinant AR (r-AR) to confirm cell function and we introduced
      antibody array analysis to investigate pathways of AR activation. The results
      showed that AR can promote migratory activity and Dox resistance through
      activation of the MAPK pathway. Whereas the inhibition of the MAPK pathway has
      the potential to inhibit chondrosarcoma cell migration, p38 inhibition, and ERK
      activation may render cells more sensitive to Dox. These findings suggest that
      combining AR with MAPK blockade may effectively treat chondrosarcoma.

PMID- 30230034
TI  - Unraveling the molecular effect of a rare missense mutation in BRIP1 associated
      with inherited breast cancer.
AB  - BRIP1 is a component of the Fanconi Anemia/BRCA pathway responsible for DNA
      reparation via helicase activity. Some heterozygous variants in BRIP1 could
      contribute to Hereditary Breast Cancer through a defective DNA repair. The
      clinical utility of BRIP1 mutations in a familial cancer context is compromised
      by the conflicting interpretation of "variants of uncertain significance" (VUS).
      Defining the clinical significance of variants identified in genetic tests is a
      major challenge; therefore, studies that evaluate the biological effect of these
      variants are definitely necessary. To contribute to this purpose, we have
      characterized the variant c.550G>T of BRIP1, a missense mutation with little
      evidence about its pathogenicity. Since Human Splicing FinderTM predicts the
      creation of a new exonic splicing enhancer site we decided to perform cDNA
      analysis revealing that the c.550G>T mutation located in exon 6 led to an
      aberrant transcript causing exon 5 skipping. Our results demonstrate that the
      c.550G>T BRIP1 variant disrupts normal splicing, causing exon 5 skipping.
      Considering that the exon 5 encodes the helicase domain of BRIP1, it is expected
      an alteration of the function. This finding enhances the interpretation of this
      VUS, suggesting a potential pathogenic effect.

PMID- 30230035
TI  - HIF-1alpha-mediated BMP6 down-regulation leads to hyperproliferation and abnormal
      differentiation of keratinocytes in vitro.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) has been reported to be up-regulated
      in psoriatic epidermis, resulting in increased proliferation and abnormal
      differentiation of human keratinocytes (KCs). However, the role of HIF-1alpha in
      psoriatic epidermis, which is mainly composed of KCs, is poorly understood. Here,
      we show that morphogenic protein 6 (BMP6) is down-regulated when HIF-1alpha is
      upregulated in patients with psoriasis skin lesions. HIF-1alpha overexpression in
      primary human KCs promoted proliferation and inhibited terminal differentiation.
      Furthermore, HIF1-alpha repressed the expression of BMP6 by binding directly to
      the hypoxia-response element (HRE) in the BMP6 promotor region, which shows that
      BMP6 is a novel target gene of HIF-1alpha. We also found that HIF-1alpha-mediated
      BMP6 suppression could alter the proliferation status by modulating the
      expression levels of cell cycle regulatory proteins and also affect the early
      differentiation of KCs. Therefore, we suggest that HIF-1alpha-dependent BMP6
      suppression has a critical role in the induction of hyper-proliferation and
      abnormal differentiation in psoriatic KCs.

PMID- 30230037
TI  - How sprinters accelerate beyond the velocity plateau of soccer players: Waveform
      analysis of ground reaction forces.
AB  - Forces applied to the ground during sprinting are vital to performance. This
      study aimed to understand how specific aspects of ground reaction force waveforms
      allow some individuals to continue to accelerate beyond the velocity plateau of
      others. Twenty-eight male sprint specialists and 24 male soccer players performed
      maximal-effort 60-m sprints. A 54-force-plate system captured ground reaction
      forces, which were used to calculate horizontal velocity profiles. Touchdown
      velocities of steps were matched (8.00, 8.25, and 8.50 m/s), and the subsequent
      ground contact forces were analyzed. Mean forces were compared across groups and
      statistical parametric mapping (t tests) assessed for differences between entire
      force waveforms. When individuals contacted the ground with matched horizontal
      velocity, ground contact durations were similar. Despite this, sprinters produced
      higher average horizontal power (15.7-17.9 W/kg) than the soccer players (7.9
      11.9 W/kg). Force waveforms did not differ in the initial braking phase (0%-~20%
      of stance). However, sprinters attenuated eccentric force more in the late
      braking phase and produced a higher antero-posterior component of force across
      the majority of the propulsive phase, for example, from 31%-82% and 92%-100% of
      stance at 8.5 m/s. At this velocity, resultant forces were also higher (33%-83%
      and 86%-100% of stance) and the force vector was more horizontally orientated
      (30%-60% and 95%-98% of stance) in the sprinters. These findings illustrate the
      mechanisms which allowed the sprinters to continue accelerating beyond the soccer
      players' velocity plateau. Moreover, these force production demands provide new
      insight regarding athletes' strength and technique training requirements to
      improve acceleration at high velocity.

PMID- 30230036
TI  - Association between the "Timed Up and Go Test" at transplant evaluation and
      outcomes after kidney transplantation.
AB  - BACKGROUND: Studies have demonstrated the Timed Up and Go Test's (TUGT) ability
      to forecast postoperative outcomes for several surgical specialties. Evaluations
      of the TUGT for waitlist and posttransplant outcomes have yet to be examined in
      kidney transplantation. OBJECTIVE: To assess the prognostic utility of the TUGT
      and its associations with waitlist and posttransplant outcomes for kidney
      transplant candidates. DESIGN AND METHODS: Single-center, prospective study of
      518 patients who performed TUGT during their transplant evaluation between
      9/1/2013-11/30/2014. TUGT times were evaluated as a continuous variable or 3
      level discrete categorical variable with TUGT times categorized as long (>9
      seconds), average (8-9 seconds), or short (5-8 seconds). RESULTS: Transplanted
      individuals had shorter TUGT times than those who remained on the waitlist (8.99
      vs 9.79 seconds, P < 0.001). Bivariable and multivariable logistic regression
      showed that after adjusting for age, there was no association between TUGT times
      and probability of waitlist removal (OR 0.997 [0.814-1.221]), prolonged length of
      stay posttransplant (OR 1.113 [0.958-1.306] for deceased donor, OR 0.983 [0.757
      1.277] for living donor), and 30-day readmissions (OR 0.984 [0.845-1.146] for
      deceased donor, OR 1.254 [0.976-1.613] for living donor). CONCLUSIONS: The TUGT
      was not associated with waitlist removal or prolonged hospitalization for kidney
      transplant candidates. Alternative assessments of global health, such as
      functional status or frailty, should be considered for evaluation of potential
      kidney transplant candidates.

PMID- 30230038
TI  - Inhibition of mTOR in head and neck cancer cells alters endothelial cell
      morphology in a paracrine fashion.
AB  - Head and neck squamous cell carcinoma (HNSCC) represent aggressive classes of
      tumors with a high mortality rate. The mammalian target of rapamycin (mTOR)
      pathway is instrumental in their initiation and expansion. Although results from
      pre-clinical models promise mTOR targeting as a potent novel therapeutic
      approach, its impact on the tumor microenvironment, such as endothelial cells is
      only scarcely investigated. Here, we first confirmed the effects of mTOR
      pharmacological inhibition on cell viability, clonogenicity, and proliferation in
      HNSCC human cell lines, HN26, and HN30. While Everolimus and Torin1 potently
      blunted mTOR-based proliferation of HN26 and HN30 lines, endothelial cells were
      left intact. To further explore the possibility of a paracrine bystander action
      of HNSCC-treated cells on endothelial cells, conditioned medium from Everolimus-
      and Torin1-challenged HN26 and HN30 cells were collected and applied to naive
      human endothelial cells. Although endothelial cell viability was again not
      modified, morphology and mobility were changed. Indeed, spreading of endothelial
      cells was altered upon challenge with mTOR-pretreated tumor conditioned-media, as
      measured via cell impedance and imagery. Interestingly, this was associated with
      an augmentation of focal adhesion kinase (FAK) active phosphorylation and
      enhanced migratory behavior. From a molecular standpoint, the production of
      vascular endothelial growth factor was elevated in treated HNSCC cells and might
      contribute to FAK phosphorylation. Although mTOR inhibition in tumor cells did
      hinder their growth, it also favors the release of factors that subsequently
      enable endothelial cell migration. Further studies will address how this
      paracrine action may affect tumor-driven angiogenesis upon pharmacological
      treatments.

PMID- 30230039
TI  - Effects of quorum-sensing inhibition on experimental periodontitis induced by
      mixed infection in mice.
AB  - This study aimed to verify, in in vivo settings, whether quorum-sensing
      inhibition molecules could attenuate alveolar bone loss induced by Porphyromonas
      gingivalis/Fusobacterium nucleatum co-infection and reduce the bacterial
      colonization of periodontal tissues. In BALB/c mice, periodontitis was induced
      through oral inoculation with P. gingivalis and F. nucleatum six times during a
      42-d period. Quorum sensing inhibitors (a furanone compound and D-ribose) were
      administered simultaneously with bacterial infection. Linear and volumetric
      modifications of interproximal alveolar bone levels were compared between groups
      using micro-computed tomography. Total bacteria, and P. gingivalis and F.
      nucleatum DNA in periodontal tissues, were quantified using real-time PCR.
      Radiographic linear measurements demonstrated a significant reduction of alveolar
      bone loss, of approximately 40%, in mice treated with quorum sensing inhibitors
      when compared with the co-infection group. This was confirmed by a significant
      increase of residual bone volume in the test group. While total bacterial genes
      in the treatment group significantly decreased by 93% in periodontal tissue
      samples when quorum sensing inhibitors were administered, no significant
      differences of P. gingivalis DNA were found. Quorum sensing inhibitors reduced
      periodontal breakdown and bacterial infection in periodontal tissues after co
      infection with P. gingivalis and F. nucleatum.

PMID- 30230040
TI  - Down-regulated SHARPIN may accelerate the development of atopic dermatitis
      through activating interleukin-33/ST2 signalling.
AB  - SHARPIN is an important component of the linear ubiquitin chain assembly complex
      (LUBAC). Loss of function of SHARPIN results in eosinophilic inflammation in
      multiple organs including skin with Th2 -dominant cytokines and dysregulated
      development of lymphoid tissues in mice. The clinicopathological features are
      similar to atopic dermatitis (AD) in humans. In order to investigate the
      potential role of SHARPIN in the pathogenesis of AD, we performed genetic
      association study of the genotypes and haplotypes as well as SHARPIN's expression
      between AD cases and controls. We found three mutations (g.480G>A, g.4576A>G and
      g.5070C>T) in patient group, and significantly decreased expression in AD
      lesions, suggesting a primary role of SHARPIN during AD development. Lentivirus
      mediated in vitro assays identified that knockdown of SHARPIN can induce elevated
      expression of IL-33 and its orphan receptor ST2, FLG and STAT3 and NF-kappaB
      inactivation in HaCaT keratinocytes, which has been widely evidenced in
      regulating AD development. ST2 expression was highly induced in SHARPIN-silenced
      HaCaT keratinocytes after the combined stimulation of IL-4 and IL-13. Our in vivo
      and in vitro findings implicated that SHARPIN may be a novel participant in the
      pathogenesis and/or new therapeutic target of AD.

PMID- 30230041
TI  - Virtual reality exercise intradialysis to improve physical function: A
      feasibility randomized trial.
AB  - OBJECTIVE: The main objective of this investigation was to assess feasibility of
      conducting a future RCT with an intradialysis non-immersive virtual reality
      exercise intervention. The secondary aim was to explore the impact of either
      conventional or VR exercise on physical function. DESIGN: Feasibility randomized
      trial. PARTICIPANTS: Eighteen subjects who participated in a 16-week
      intradialysis combined exercise program. INTERVENTIONS: The program lasted four
      additional weeks of either combined exercise or virtual reality exercise. MAIN
      OUTCOME MEASURES: Physical function was measured through several reliable tests
      (sit-to-stand-to-sit tests 10 and 60, gait speed, one-leg heel-rise tests, and 6
      minute walk test) at baseline, after 16 weeks of intradialysis combined exercise
      and by the end of four additional weeks of exercise. Adherence to the exercise
      programs was registered. RESULTS: There was a significant time effect, so that
      physical function improved in both groups. By the end of the 20 weeks, function
      improved as measured through the sit-to-stand-to-sit tests 10 and 60, gait speed,
      one-leg heel-rise left leg, and the 6-minute walk test. Changes that did not
      occur due to error in the test were seen after 20 weeks were achieved in the sit
      to-stand-to-sit test 60, gait speed, one-leg heel-rise test for the left leg, and
      6-minute walking test. CONCLUSION: Virtual reality was a feasible intervention.
      Both interventions improved physical function. Adherence was not significantly
      different between groups.

PMID- 30230042
TI  - High-density electromyography activity in various hamstring exercises.
AB  - Proximal-distal differences in muscle activity are rarely considered when
      defining the activity level of hamstring muscles. The aim of this study was to
      determine the inter-muscular and proximal-distal electromyography (EMG) activity
      patterns of hamstring muscles during common hamstring exercises. Nineteen amateur
      athletes without a history of hamstring injury performed 9 exercises, while EMG
      activity was recorded along the biceps femoris long head (BFlh) and
      semitendinosus (ST) muscles using 15-channel high-density electromyography (HD
      EMG) electrodes. EMG activity levels normalized to those of a maximal voluntary
      isometric contraction (%MVIC) were determined for the eccentric and concentric
      phase of each exercise and compared between different muscles and regions
      (proximal, middle, distal) within each muscle. Straight-knee bridge, upright hip
      extension, and leg curls exhibited the highest hamstrings activity in both the
      eccentric (40%-54%MVIC) and concentric phases (69%-85%MVIC). Hip extension was
      the only BF-dominant exercise (Cohen's d = 0.28 (eccentric) and 0.33
      (concentric)). Within ST, lower distal than middle/proximal activity was found in
      the bent-knee bridge and leg curl exercises (d range = 0.53-1.20), which was not
      evident in other exercises. BFlh also displayed large regional differences across
      exercises (d range = 0.00-1.28). This study demonstrates that inter-muscular and
      proximal-distal activity patterns are exercise-dependent, and in some exercises
      are affected by the contraction mode. Knowledge of activity levels and relative
      activity of hamstring muscles in different exercises may assist exercise
      selection in hamstring injury management.

PMID- 30230043
TI  - Tolerability of isavuconazole after posaconazole toxicity in leukaemia patients.
AB  - BACKGROUND: Posaconazole (PCZ) is widely used for prophylaxis or treatment of
      invasive fungal infections (IFIs) in leukaemia patients. However, issues with PCZ
      tolerability can result in treatment interruption. Isavuconazole (ISA) has a
      similar broad spectrum of activity to PCZ; however, real-world data regarding the
      tolerability of ISA after PCZ toxicity are lacking. OBJECTIVES: To describe the
      tolerability of ISA after PCZ toxicity in leukaemia patients. PATIENTS/METHODS:
      We retrospectively assessed tolerability of ISA after PCZ toxicity in adult
      leukaemia patients (March 2015 to November 2017). We included all patients who
      received >=7 days of ISA within 48 hours of PCZ discontinuation. Laboratory
      markers for liver toxicity were collected at three time points: prior to PCZ, at
      switch to ISA and after ISA therapy. RESULTS: We identified 23 such patients.
      Increased liver function tests (LFTs) were noted in 20 patients on PCZ, while
      three patients had Grade 3/4 QTc prolongation. No patient discontinued subsequent
      ISA due to toxicity. Grade 3/4 elevations in LFTs were decreased after changing
      to ISA (30% after PCZ vs 5% after ISA). No patient had significant QTc
      prolongation after switching to ISA. CONCLUSIONS: Isavuconazole was well
      tolerated in patients discontinuing PCZ due to toxicity, with no patient
      discontinuing ISA due to toxicity.

PMID- 30230044
TI  - Cutaneous infections by dematiaceous opportunistic fungi: Diagnosis and
      management in 11 solid organ transplant recipients.
AB  - BACKGROUND: The incidence of cutaneous infections by dematiaceous fungi is rising
      in our environment due to the high number of solid organ transplant recipients
      (SOTR). OBJECTIVE: To review our experience in the management of cutaneous
      phaeohyphomycoses in a Spanish reference centre for dermatological care of SOTR.
      METHODS: Retrospective clinical, histopathological and microbiological review of
      all SOTR diagnosed of a phaeohyphomycosis in a 7-year period. RESULTS: Eleven
      SOTR were identified (8 lung and 3 kidney). The lesions were solitary in six
      patients and multiple in five, affecting mostly the lower extremities. Early
      lesions showed epidermal hyperplasia and a diffuse dermal suppurative
      granulomatous infiltrate that was progressively substituted by fibrosis when the
      lesions were treated. Septated fungal structures with refractile walls were
      identified. DNA sequencing confirmed the presence of Alternaria spp (8 cases),
      Cladosporium cladosporioides, Microsphaeropsis arundinis and Exophiala
      oligosperma. Three patients with single lesions were treated with surgery, while
      the other 8 required long-term antifungal therapy, including itraconazole,
      voriconazole and/or terbinafine, combined with surgery and reduction in
      tacrolimus doses. CONCLUSION: A clinical, histopathological and microbiological
      correlation is essential to corroborate this diagnosis. Solitary lesions are
      easily treated with surgery, but larger or multiple lesions may require long
      medical treatments combined with surgery and modification of immunosuppressive
      medication. The list of dematiaceous fungi implicated in cutaneous infections is
      expanding, in line with the availability of more sophisticated identification
      methods and the increasing number of immunosuppressed patients.

PMID- 30230045
TI  - Causes and Solutions of Recombination in Perovskite Solar Cells.
AB  - Organic-inorganic hybrid perovskite materials are receiving increasing attention
      and becoming star materials on account of their unique and intriguing optical and
      electrical properties, such as high molar extinction coefficient, wide absorption
      spectrum, low excitonic binding energy, ambipolar carrier transport property,
      long carrier diffusion length, and high defects tolerance. Although a high power
      conversion efficiency (PCE) of up to 22.7% is certified for perovskite solar
      cells (PSCs), it is still far from the theoretical Shockley-Queisser limit
      efficiency (30.5%). Obviously, trap-assisted nonradiative (also called Shockley
      Read-Hall, SRH) recombination in perovskite films and interface recombination
      should be mainly responsible for the above efficiency distance. Here, recent
      research advancements in suppressing bulk SRH recombination and interface
      recombination are systematically investigated. For reducing SRH recombination in
      the films, engineering perovskite composition, additives, dimensionality, grain
      orientation, nonstoichiometric approach, precursor solution, and post-treatment
      are explored. The focus herein is on the recombination at perovskite/electron
      transporting material and perovskite/hole-transporting material interfaces in
      normal or inverted PSCs. Strategies for suppressing bulk and interface
      recombination are described. Additionally, the effect of trap-assisted
      nonradiative recombination on hysteresis and stability of PSCs is discussed.
      Finally, possible solutions and reasonable prospects for suppressing
      recombination losses are presented.

PMID- 30230046
TI  - Biofunctionalization of Nano Channels by Direct In-Pore Solid-Phase Peptide
      Synthesis.
AB  - Diatom biosilica are highly complex inorganic/organic hybrid materials. To get
      deeper insights on their structure at a molecular level, model systems that mimic
      the complex natural compounds were synthesized and characterized. A simple and
      efficient peptide immobilization strategy was developed, which uses a well
      ordered porous silica material as a support and commercially available Fmoc-amino
      acids, similar to the known solid-phase peptide synthesis. As an example, Fmoc
      glycine and Fmoc-phenylalanine are immobilized on the silica support. The success
      of functionalization was investigated by 13 C CP MAS and 29 Si CP MAS solid-state
      NMR. Thermogravimetric analysis (TGA) and elemental analysis (EA) were performed
      to quantify the functionalization. Changes of the specific surface area, pore
      volume, and pore diameters in all modification steps were studied by Brunauer
      Emmett-Teller based nitrogen adsorption-desorption measurements (BET). The
      combination of the analytical methods provided high grafting densities of 2.1+/
      0.2 molecules/nm2 on the surface. Furthermore, they allowed for monitoring
      chemical changes on the pore surface and changes of the pore properties of the
      material during the different functionalization steps. This universal approach is
      suitable for the selective synthesis of pores with tunable surface-peptide
      functionalization, with applications to the synthesis of a big variety of silica
      peptide model systems, which in the future may lead to a deeper understanding of
      complex biological systems.

PMID- 30230048
TI  - Endoscopic selective muscular dissection for gastric submucosal tumor.

PMID- 30230047
TI  - Clarithromycin added to bortezomib-cyclophosphamide-dexamethasone impairs health
      related quality of life in multiple myeloma patients.
AB  - OBJECTIVES: The Danish Myeloma Study Group initiated a randomized, placebo
      controlled, double-blinded phase II study to investigate the efficacy of adding
      clarithromycin to cyclophosphamide-bortezomib-dexamethasone (VCD) induction
      therapy in transplant eligible, newly diagnosed multiple myeloma patients. The
      study was prematurely terminated due to severe complications, and no effect of
      adding clarithromycin was found. The aim of this study was to compare health
      related quality of life (HRQoL) between the two groups and to explore the
      coherence hereof with adverse event (AE) registration by clinicians. METHODS:
      Patients completed three validated HRQoL questionnaires at inclusion, before
      cyclophosphamide priming, and two months after high-dose therapy (HDT). The mean
      score difference was interpreted by clinically relevant differences between
      groups. Spearman's correlation analysis was used to compare patient-reported
      toxicities with AEs. RESULTS: Of 58 included patients, 55 participated in the
      HRQoL reporting. Before cyclophosphamide priming, patients in the clarithromycin
      group reported clinically relevant reduced HRQoL for eleven domains with
      persistent reduction in four domains two months after HDT. Poor correlation
      between patient-reported toxicities and clinician-reported AEs was observed.
      CONCLUSIONS: Despite the premature study termination, our data demonstrate
      impaired HRQoL when clarithromycin was added to the VCD regimen. We found clear
      underreporting of toxicities by clinicians. ClinicalTrials.gov number
      NCT02573935.

PMID- 30230049
TI  - A study of coach-team perceptual distance concerning the coach-created
      motivational climate in youth sport.
AB  - The purpose of this study was to examine whether coach-team perceptual distance
      regarding the coach-created motivational climate related to achievement goal
      orientations and affective responses. To this end, we used polynomial regression
      analysis with response surface methodology. The sample consisted of 1359 youth
      soccer players (57.8% male; Mage  = 11.81 years, SD = 1.18), belonging to 87
      different teams (Msize  = 16.47), and 87 coaches (94.6% male, Mage  = 42 years,
      SD = 5.67). Results showed that team perceptions of a coach-created mastery
      climate were positively related to team-rated task goal orientation and
      enjoyment, whereas team perceptions of a coach-created performance climate were
      positively related to team-rated ego goal orientation and anxiety, and negatively
      related to team-rated enjoyment. When the coach and the team were in perceptual
      agreement, the outcomes increased as both coach and team perceptions of the
      climate increased. In situations of perceptual disagreement, the most negative
      effects were seen when the coach held a more favorable perception of the
      motivational climate compared to the team. The findings highlight the importance
      of perceptual agreement between the coach and his/her team, contributing to the
      literature focusing on the effects of the coach-created motivational climate.

PMID- 30230050
TI  - Corroles at the Real Solid-Liquid Interface: In Situ STM Investigation of a Water
      Soluble Corrole Layer Deposited onto Au(111).
AB  - Corrole derivatives have been recently employed in many applications at the solid
      liquid interface. Therefore, the structural arrangement of the molecular layers
      in direct contact with the liquid is of fundamental interest. We investigated in
      solution the deposition of molecular layers of the previously prepared water
      soluble phosphorus complex of a 2-sulfonato-10-(4-sulfonatophenyl)-5,15
      dimesitylcorrole [see synthesis in our previous paper, M. Naitana et al., Chem.
      Eur. J. 2017, 23, 905-916]. The layer formation of P corroles onto the Au(111)
      surface was monitored by STM in situ, that is, with the substrate immersed in the
      solution. Marked differences in the morphology between the organic layer formed
      on the substrate and that deposited after solvent evaporation (drop casting) are
      reported. In particular, the coating of gold was more effective and stable in the
      presence of liquid. Preservation of functionality of the corrole molecules after
      adsorption was verified. This result validates the relevance of corrole layers at
      the solid-liquid interface to exploit the peculiar properties of these molecules
      in real-world applications.

PMID- 30230051
TI  - The house dust mite allergen Der p 5 binds lipid ligands and stimulates airway
      epithelial cells through a TLR2-dependent pathway.
AB  - BACKGROUND: Protein crystallographic studies suggest that the house dust mite
      (HDM) allergen Der p 5 potentially interacts with hydrophobic ligands. Der p 5,
      in association with its ligand(s), might therefore trigger innate immune
      signalling pathways in the airway epithelium and influence the initiation of the
      HDM-allergic response. OBJECTIVE: We investigated the lipid binding propensities
      of recombinant (r)Der p 5 and characterized the signalling pathways triggered by
      the allergen in airway epithelial cells. METHODS: rDer p 5 was produced in Pichia
      pastoris and characterized by mass spectrometry, multi-angle light scattering and
      circular dichroism. Its interactions with hydrophobic ligands were investigated
      in fluorescence-based lipid binding assays and in-silico docking simulations.
      Innate immune signalling pathways triggered by rDer p 5 were investigated in
      airway epithelial cell activation assays in vitro. RESULTS: Biophysical analysis
      showed that rDer p 5 was monomeric and adopted a similar alpha-helix-rich fold at
      both physiological and acidic pH. Spectrofluorimetry experiments showed that rDer
      p 5 is able to selectively bind lipid ligands, but only under mild acidic pH
      conditions. Computer-based docking simulations identified potential binding sites
      for these ligands. This allergen, with putatively associated lipid(s), triggered
      the production of IL-8 in respiratory epithelial cells through a TLR2-, NF-kB-
      and MAPK-dependent signalling pathway. CONCLUSIONS AND CLINICAL RELEVANCE:
      Despite the fact that Der p 5 represents a HDM allergen of intermediate
      prevalence, our findings regarding its lipid binding and activation of TLR2
      indicate that it could participate in the initiation of the HDM-allergic state.

PMID- 30230052
TI  - Effects of barbell back squat stance width on sagittal and frontal hip and knee
      kinetics.
AB  - Different stance widths are commonly utilized when completing the barbell back
      squat during athletic general preparedness training. Width manipulation is
      thought to influence sagittal plane stimuli to the hip and knee extensors, the
      primary extensor musculature in the squat. However, how width manipulation
      affects frontal plane stimuli is less understood. Knowledge of hip and knee net
      joint moments (NJM) could improve exercise selection when aiming to improve sport
      specific performance and prevent injuries. Fourteen adult amateur rugby athletes
      were recruited for this study. After a familiarization period, participants
      performed wide- (WIDE, 1.5* greater trochanter width) and narrow-stance (NARROW,
      1* greater trochanter width) barbell back squats to femur parallel depth, using
      relative loads of 70% and 85% of one-repetition maximum. Sagittal and frontal
      plane hip and knee kinetics and kinematics were compared between widths. A
      Bonferroni-corrected alpha of 0.01 was employed as the threshold for statistical
      significance. Knee flexion angle was statistically greater in NARROW than WIDE (P
      < 0.0001, d = 2.56-2.86); no statistical differences were observed for hip
      flexion angle between conditions (P = 0.049-0.109, d = 0.33-0.38). Hip-to-knee
      extension NJM ratios and knee adduction NJMs were statistically greater in WIDE
      than NARROW (P < 0.007, d = 0.51-1.41). At femur parallel, stance width
      manipulation in the barbell back squat may provide substantial differences in
      biomechanical stimulus in both the sagittal plane and the frontal plane. In
      certain contexts, these differences may have clinically relevant longitudinal
      implications, from both a performance and a injury prevention standpoint, which
      are discussed.

PMID- 30230053
TI  - Mortality in liver transplant recipients with portal vein thrombosis - an updated
      meta-analysis.
AB  - Portal vein thrombosis (PVT) is the most common thrombotic event in liver
      transplant (LT) recipients, but its impact on mortality after LT has been
      analyzed in heterogeneous cohorts with mixed results. To conduct a meta-analysis
      on the impact of PVT on post-LT survival. A systematic search was conducted on
      studies (published from January 1986 to January 2018) that reported 30-day and 1
      year mortality after LT of PVT patients. Four hundred twenty-seven articles were
      reviewed and 44 were included. Among 98 558 LT, 7257 (7.3%) involved patients
      with PVT. The mean quality was high (7.1 on the Newcastle-Ottawa scale). The 30
      day pooled mortality rate was higher for patients with PVT (64/490; 13%) than for
      others (259/3357; 7%) (OR 2.29; 95% CI 1.43-3.68; P < 0.0001). One-year mortality
      was likewise higher in recipients with (853/6302; 13.5%) than in those without
      PVT (7476/75 355; 9.9%) (OR 1.38; 95% CI 1.14-1.66; P < 0.0001). Heterogeneity
      wasn't significant (I2 46% and 65%). Patients whose PVT was complete had a higher
      30-day pooled mortality rate (OR 5.65; 95% CI 2-15.96; P < 0.0001), and a 1-year
      mortality rate (OR 2.48; 95% CI 0.99-6.17; P = 0.38) than patients with partial
      PVT. PVT is common in LT candidates and it is associated with higher short- and
      medium-term mortality after LT.

PMID- 30230055
TI  - Symposium: Personalized Medicine.

PMID- 30230054
TI  - Chiral [MnII MnIII 3 M'] (M'=NaI , CaII , MnII ) and [MnII MnIII 6 NaI 2 ]
      Clusters Built from an Enantiomerically Pure Schiff Base: Synthetic, Chiroptical,
      and Magnetic Properties.
AB  - From the reaction of manganese halides with the chiral Schiff bases obtained by
      condensation of o-vanillin and (R)- or (S)-phenylglycinol, 11 complexes based on
      pentanuclear cages with trigonal bipyramidal [MnII MnIII 3 M'] (M'=NaI , CaII ,
      MnII ) or enneanuclear [MnII MnIII 6 NaI 2 ] cores were synthesized. Structural,
      supramolecular chirality, and optical properties were explored. The magnetic
      properties of related systems were reviewed, and the magnetic response of the new
      systems was rationalized to the bond parameters.

PMID- 30230056
TI  - A universal geochemical scenario for formamide condensation and prebiotic
      chemistry.
AB  - The condensation of formamide has been shown to be a robust chemical pathway
      affording molecules necessary for the origin of life. It has been experimentally
      demonstrated that condensation reactions of formamide are catalyzed by a number
      of minerals, including silicates, phosphates, sulfides, zirconia and borates, and
      by cosmic dusts and meteorites. However, a critical discussion of the catalytic
      power of the tested minerals, and the geochemical conditions under which the
      condensation would occur, is still missing. We show here that mineral self
      assembled structures forming under alkaline silica-rich solutions are excellent
      catalysts for the condensation of formamide as compared to other minerals. We
      also propose that these structures were likely forming as early as 4.4 billion
      years ago when the whole Earth surface was a reactor, a global scale factory,
      releasing large amounts of organic compounds. Our experimental results suggest
      that the conditions required for the synthesis of the molecular bricks from which
      life self-assembles, rather than being local and bizarre, appears to be universal
      and geologically rather conventional.

PMID- 30230057
TI  - Azolate Anions in Ionic Liquids: Promising and Under-Utilized Components of the
      Ionic Liquid Toolbox.
AB  - Owing to their ease of synthesis, diffuse positive charge, and chemical
      stability, 1-alkyl-3-methylimidazolium cations (i.e., [Cn mim]+ ) are one of the
      most routinely utilized and historically important components in ionic liquid
      (IL) chemistry. However, while this is a routinely encountered member of the IL
      family as cations, relatively few workers have explored the versatile chemistry
      of azoles to allow their use as an anionic component in ILs, as azolates. Azolate
      anions possess many of the desired properties for IL formation, including a
      diffuse ionic charge, tailorable asymmetry, and synthetic flexibility, with the
      added advantages of not relying on halogen atoms for electron-withdrawing
      effects, as is commonly encountered with IL anions such as hexafluorophosphate.
      This review explores the 122 azolate-containing ILs known in the literature
      (prepared from only 39 disparate azolate anions), with a view to highlighting not
      only their demonstrated utility as an IL component, but the ways in which the
      larger scientific community may utilize their advantageous properties for new
      tailored materials.

PMID- 30230058
TI  - Li2 BaSc(BO3 )2 F and LiBa2 Pb(BO3 )2 F with Layered Structures featuring Special
      Li-O/F Configurations.
AB  - Two new borate fluorides, Li2 BaSc(BO3 )2 F and LiBa2 Pb(BO3 )2 F, with layered
      structures featuring special Li-O/F configurations have been successfully
      prepared by the high-temperature solution method. Li2 BaSc(BO3 )2 F contains the
      first reported 2 infinity [Li2 (BO3 )2 F] double layers that are evolved from 2
      infinity [Be2 BO3 F2 ] single layers in KBe2 BO3 F2 through substituting BeO4
      with the LiO3 F tetrahedra. The adjacent double layers are tightly connected by
      strong Sc-O bonds, generating the strongest interlayer bond and smallest
      interlayer distance among KBe2 BO3 F2 derivatives with double-layered structures.
      LiBa2 Pb(BO3 )2 F features 2 infinity [Li(BO3 )2 F] single layers built up of
      special LiO4 F2 octahedra and the BO3 triangles. To our best knowledge, the LiO4
      F2 octahedron is observed for the first time in borates. Besides, the LiO4 F2
      octahedra construct unique 1 infinity [LiO4 F] straight chains through sharing
      apical F atoms, which is different from the configurations of the similar six
      coordinated LiO6 octahedra in other borates.

PMID- 30230059
TI  - Multifunctional Compounds for Activation of the p53-Y220C Mutant in Cancer.
AB  - The p53 protein plays a major role in cancer prevention, and over 50 % of cancer
      diagnoses can be attributed to p53 malfunction. The common p53 mutation Y220C
      causes local protein unfolding, aggregation, and can result in a loss of Zn in
      the DNA-binding domain. Structural analysis has shown that this mutant creates a
      surface site that can be stabilized using small molecules, and herein a
      multifunctional approach to restore function to p53-Y220C is reported. A series
      of compounds has been designed that contain iodinated phenols aimed for
      interaction and stabilization of the p53-Y220C surface cavity, and Zn-binding
      fragments for metallochaperone activity. Their Zn-binding affinity was
      characterized using spectroscopic methods and demonstrate the ability of
      compounds L4 and L5 to increase intracellular levels of Zn2+ in a p53-Y220C
      mutant cell line. The in vitro cytotoxicity of our compounds was initially
      screened by the National Cancer Institute (NCI-60), followed by testing in three
      stomach cancer cell lines with varying p53 status', including AGS (WTp53), MKN1
      (V143A), and NUGC3 (Y220C). Our most promising ligand, L5, is nearly 3-fold more
      cytotoxic than cisplatin in a large number of cell lines. The impressive
      cytotoxicity of L5 is further maintained in a NUGC3 3D spheroid model. L5 also
      induces Y220C-specific apoptosis in a cleaved caspase-3 assay, reduces levels of
      unfolded mutant p53, and recovers p53 transcriptional function in the NUGC3 cell
      line. These results show that these multifunctional scaffolds have the potential
      to restore wild-type function in mutant p53-Y220C.

PMID- 30230060
TI  - Multidisciplinary approach to the management of adult eosinophilic oesophagitis
      in the United Kingdom.

PMID- 30230061
TI  - Both toxic and beneficial effects of pyocyanin contribute to the lifecycle of
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa, an opportunistic pathogen, produces redox-active pigments
      called phenazines. Pyocyanin (PYO, the blue phenazine) plays an important role
      during biofilm development. Paradoxically, PYO auto-poisoning can stimulate cell
      death and release of extracellular DNA (eDNA), yet PYO can also promote survival
      within biofilms when cells are oxidant-limited. Here, we identify the
      environmental and physiological conditions in planktonic culture that promote PYO
      mediated cell death. We demonstrate that PYO auto-poisoning is enhanced when
      cells are starved for carbon. In the presence of PYO, cells activate a set of
      genes involved in energy-dependent defenses, including: (i) the oxidative stress
      response, (ii) RND efflux systems and (iii) iron-sulfur cluster biogenesis
      factors. P. aeruginosa can avoid PYO poisoning when reduced carbon is available,
      but blockage of adenosine triphosphate (ATP) synthesis either through carbon
      limitation or direct inhibition of the F0 F1 -ATP synthase triggers death and
      eDNA release. Finally, even though PYO is toxic to the majority of the population
      when cells are nutrient limited, a subset of cells is intrinsically PYO
      resistant. The effect of PYO on the producer population thus appears to be
      dynamic, playing dramatically different yet predictable roles throughout distinct
      stages of growth, helping rationalize its multifaceted contributions to biofilm
      development.

PMID- 30230063
TI  - Identification of rhinoceros keratin using direct analysis in real time time-of
      flight mass spectrometry and multivariate statistical analysis.
AB  - RATIONALE: Trade in rhinoceros horn is regulated or banned internationally in
      recognition of its impact on wild populations worldwide. Enforcement of the laws
      and regulations depends on successfully identifying when violations occur, which
      is complicated by the presence of alternative/imitation rhinoceros horn keratin
      (e.g., bovid horn keratin). In this study, we assess the potential for Direct
      Analysis in Real Time (DART) ionization paired with Time-Of-Flight Mass
      Spectrometry (DART-TOFMS) to classify different keratin types from four taxonomic
      groups: rhinoceros, bovid, domestic horse, and pangolin. METHODS: The spectra of
      156 keratin samples from all five rhinoceros species (horn keratin), eight genera
      of bovids (horn keratin), domestic horses (hoof keratin), and all extant species
      of pangolins (scale keratin) were collected. Fisher ratio analysis identified the
      most important ions that characterized each class and these ions were used for
      the training model, which consisted of 143 spectra. Kernel Discriminant Analysis
      (KDA) was used to classify the different groups. RESULTS: The spectra collected
      for each taxonomic group are distinctive. The chemotypes demonstrate that the
      spectra of rhinoceros, bovids, and domestic horse are similar to each other,
      whereas the chemotypes of pangolins show a different chemical profile. The model
      built by KDA resolved each taxonomic group: 95% of samples were correctly
      assigned using leave-one-out cross validation. The 13 blind samples not used in
      model development were all correctly classified to taxonomic source. CONCLUSIONS:
      DART-TOFMS appears to be a reliable approach for taxonomic identification of
      keratin. This analysis can be carried out with a small sliver of keratin, with
      minimal sample preparation, inexpensively and quickly, making it a potential
      valuable tool for identification of rhinoceros horn and other keratin types.

PMID- 30230062
TI  - The epidemiology of non-Candida yeast isolated from blood: The Asia Surveillance
      Study.
AB  - BACKGROUND: Current guidelines recommend echinocandins as first-line therapy for
      candidemia. However, several non-Candida yeast are non-susceptible to
      echinocandins (echinocandin non-susceptible yeast, ENSY), including Cryptococcus,
      Geotrichum, Malassezia, Pseudozyma, Rhodotorula, Saprochaete, Sporobolomyces and
      Trichosporon. In laboratories that are not equipped with rapid diagnostic tools,
      it often takes several days to identify yeast, and this may lead to inappropriate
      presumptive use of echinocandins in patients with ENSY fungemia. The aim of this
      study was to determine the distribution of ENSY species during a 1-year,
      laboratory surveillance programme in Asia. METHODS: Non-duplicate yeast isolated
      from blood or bone marrow cultures at 25 hospitals in China, Hong Kong, India,
      Singapore, Taiwan and Thailand were analysed. Isolates were considered to be
      duplicative if they were obtained within 7 days from the same patient. RESULTS:
      Of 2155 yeast isolates evaluated, 175 (8.1%) were non-Candida yeast. The majority
      of non-Candida yeast were ENSY (146/175, 83.4%). These included Cryptococcus (109
      isolates), Trichosporon (23), Rhodotorula (10) and Malassezia (4). The proportion
      of ENSY isolates (146/2155, 6.7%) differed between tropical (India, Thailand and
      Singapore; 51/593, 8.6%) and non-tropical countries/regions (China, Hong Kong and
      Taiwan; 95/1562, 6.1%, P = 0.038). ENSY was common in outpatient clinics (25.0%)
      and emergency departments (17.8%) but rare in intensive care units (4.7%) and in
      haematology-oncology units (2.9%). Cryptococcus accounted for the majority of the
      non-Candida species in emergency departments (21/24, 87.5%) and outpatient
      clinics (4/5, 80.0%). CONCLUSIONS: Isolation of non-Candida yeast from blood
      cultures was not rare, and the frequency varied among medical units and
      countries.

PMID- 30230064
TI  - Peak oxygen uptake cut-points to identify children at increased cardiometabolic
      risk - The PANIC Study.
AB  - We aimed to develop cut-points for directly measured peak oxygen uptake ( VO2peak
      ) to identify boys and girls at increased cardiometabolic risk using different
      scaling methods to control for body size and composition. Altogether 352 children
      (186 boys, 166 girls) aged 9-11 years were included in the analyses. We measured
      VO2peak directly during a maximal cycle ergometer exercise test and lean body
      mass (LM) by bioelectrical impedance. We computed a sex- and age-specific
      cardiometabolic risk score (CRS) by summing important cardiometabolic risk
      factors and defined increased cardiometabolic risk as >1 standard deviation above
      the mean of CRS. Receiver operating characteristics curves were used to detect
      VO2peak cut-points for increased cardiometabolic risk. Boys with VO2peak <45.8 mL
      kg body mass (BM)-1  min-1 (95% confidence interval [CI] = 45.1 to 54.6, area
      under the curve [AUC] = 0.86, P < 0.001) and <63.2 mL kg LM-1  min-1 (95% CI
      =52.4 to 67.5, AUC = 0.65, P = 0.006) had an increased CRS. Girls with VO2peak
      <44.1 mL kg BM-1  min-1 (95% CI = 44.0 to 58.6, AUC = 0.67, P = 0.013) had an
      increased CRS. VO2peak scaled by BM-0.49 and LM-0.77 derived from log-linear
      allometric modeling poorly predicted increased cardiometabolic risk in boys and
      girls. In conclusion, directly measured VO2peak <45.8 mL kg BM-1  min-1 among
      boys and <44.1 mL kg BM-1  min-1 among girls were cut-points to identify those at
      increased cardiometabolic risk. Appropriately controlling for body size and
      composition reduced the ability of cardiorespiratory fitness to identify children
      at increased cardiometabolic risk.

PMID- 30230065
TI  - How Do Substrates Bind to a Bifunctional Thiourea Catalyst? A Vibrational CD
      Study on Carboxylic Acid Binding.
AB  - Knowledge about the active conformation of an asymmetric catalyst is highly
      valuable in order to understand its stereoinductive power, but spectroscopic
      access to these structures is often limited. For the example of Takemoto's
      bifunctional thiourea, we demonstrate the capability of VCD spectroscopy to
      characterize the conformational preferences of the catalyst with and without
      having a reactant bound to it. In particular we show that the binding orientation
      of carboxylic acids can easily be derived from a computationally guided analysis
      of the spectra. Moreover, we identify characteristic marker bands, which are only
      visible in the VCD spectra of the catalyst/acid mixtures but not in the
      corresponding IR spectra. Lastly, we also discuss the problem that the popular
      DFT functional M06-2X, which we found to perform exceptionally well in the
      calculations of vibrational frequencies for fluorinated molecules, predicts
      incorrect structures of the molecular clusters. We relate this poor performance
      in predicting the structure of the binding topologies to an overestimation of
      dispersive CH-pi and pi-pi interactions, which occur due to a neglect of the
      solvent molecules in the clusters. VCD spectroscopy is thus shown to be a
      powerful tool to identify and subsequently correct such mispredictions of
      solution-phase structures.

PMID- 30230066
TI  - Reduced Graphene Oxide Chemically Modified with Aggregation-Induced Emission
      Polymer for Solid-State Optical Limiter.
AB  - Aggregation-induced emission (AIE) materials are usually not suitable for
      constructing solid nonlinear optical (NLO) devices because strong solid-state
      aggregation behavior would shorten the excited-state lifetime, add relaxation
      pathways, and thereby reduce effective NLO absorption. To address this problem a
      newly synthesized AIE material, poly{[9,9-bis(6-azidohexyl)-9H-fluorene]-alt
      (1,1,2,2-tetraphenylethene)} (PAHFTP), was treated with reduced graphene oxide
      (RGO) to give the soluble derivative of poly[(9,9-dihexyl-9H-fluorene)-alt
      (1,1,2,2-tetraphenylethene)] (PFTP) covalently grafted onto RGO (PFTP-RGO). Upon
      covalent grafting of PAHFTP onto the RGO surface, about 91.89 % of the
      fluorescence intensity of the PAHFTP film was quenched due to electron transfer
      from PFTP to RGO, which yielded PFTP.+ -RGO.- radical-ion pairs. The as-prepared
      PFTP-RGO was embedded into a non-optically active poly(methyl methacrylate)
      (PMMA) matrix to produce the PFTP-RGO/PMMA film with good optical quality. As
      expected, the PAHFTP/PMMA film did not show any NLO response. In contrast to the
      PFTP-RGO/PMMA and RGO/PMMA films, the annealed PFTP-RGO/PMMA exhibited superior
      OL performance, with low OL thresholds of 0.24 GW cm-2 (1.44 J cm-2 ) at 532 nm
      and 0.18 GW cm-2 (1.08 J cm-2 ) at 1064 nm. The damage thresholds of the annealed
      PFTP-RGO/PMMA film are around 33.88 J cm-2 at 900 MUJ at 532 nm and 37.32 J cm-2
      at 1000 MUJ at 1064 nm, respectively.

PMID- 30230067
TI  - Improving the Halogen-Magnesium Exchange by Using new Turbo-Grignard Reagents.
AB  - This mini-review describes the scope of the halogen-magnesium exchange. It shows
      that the use of turbo-Grignard reagent (iPrMgCl.LiCl) greatly enhances the rate
      of the Br- and I-Mg exchange. Furthermore, this magnesium reagent allows the
      performance of a fast sulfoxide-magnesium exchange. Also, the use of sBuMgOR.LiOR
      (R = 2-ethylhexyl) enables a Br/Mg-exchange in toluene leading to various
      Grignard reagents in toluene. Additionally, the new exchange reagent sBu2Mg.2LiOR
      (R = 2-ethylhexyl) further increases the rate of the halogen-magnesium exchange
      allowing to perform a chlorine-magnesium exchange for aromatic chlorides bearing
      an ortho-methoxy substituent in toluene.

PMID- 30230068
TI  - Advancing the case for nurse practitioner-based models to accelerate scale-up of
      HIV pre-exposure prophylaxis.
AB  - AIMS: To explore the factors that position nurse practitioners (NPs) to lead the
      implementation of HIV pre-exposure prophylaxis. BACKGROUND: The HIV epidemic
      represents a global health crisis. Reducing new HIV infections is a public health
      priority, especially for Black and Latino men who have sex with men (MSM). When
      taken as directed, co-formulated emtricitabine and tenofovir have over 95%
      efficacy in preventing HIV; however, substantial gaps remain between those who
      would benefit from pre-exposure prophylaxis (PrEP) and current PrEP prescribing
      practices. DESIGN: This is a position paper that draws on concurrent assessments
      of research literature and advanced practice nursing frameworks. METHOD: The
      arguments in this paper are grounded in the current literature on HIV PrEP
      implementation and evidence of the added value of nurse-based models in promoting
      health outcomes. The American Association of Colleges of Nursing's advanced
      nursing practice competencies were also included as a source of data for
      identifying and cross-referencing NP assets that align with HIV PrEP care
      continuum outcomes. CONCLUSIONS: There are four main evidence-based arguments
      that can be used to advance policy-level and practice-level changes that harness
      the assets of nurse practitioners in accelerating the scale-up of HIV PrEP.
      RELEVANCE TO CLINICAL PRACTICE: Global public health goals for HIV prevention
      cannot be achieved without the broader adoption of PrEP as a prevention practice
      among healthcare providers. NPs are the best hope for closing this gap in access
      for the populations that are most vulnerable to HIV infection.

PMID- 30230069
TI  - Feasibility of DAIly NURSE: A nursing intervention to change nursing staff
      behaviour towards encouraging residents' daily activities and independence in the
      nursing home.
AB  - AIMS AND OBJECTIVES: To examine the feasibility of DAIly NURSE and a nursing
      intervention to encourage nursing home residents' daily activities and
      independence. BACKGROUND: Nursing home residents are mainly inactive during the
      day. DAIly NURSE was developed to change nursing behaviour towards encouraging
      nursing home residents' activities and independence by creating awareness. It
      consists of three components: education, coaching-on-the-job and policy. DESIGN:
      A mixed-method study. METHODS: The feasibility of DAIly NURSE in practice was
      tested in six psychogeriatric nursing home wards, using attendance lists (reach),
      evaluation questionnaires (fidelity, dose received and barriers), notes made by
      the researcher (dose delivered and fidelity) and a focus group interview (dose
      received and barriers) with nursing home staff (n = 8) at the end of the study.
      RESULTS: The feasibility study showed that all three components (education,
      coaching-on-the-job and policy) were implemented in practice. The attendance rate
      in the workshops was high (average: 82%). Nursing home staff were satisfied with
      the workshops (mean score 9 out of 10 points) and agreed that DAIly NURSE was
      feasible in daily nursing care practice. Recommendations to optimise the
      feasibility of DAIly NURSE included the following: Add video observations of a
      specific moment of the day to create awareness of nursing behaviour; educate all
      nursing staff of the ward during the workshops; and organise information meetings
      for family members before the start of the intervention. Nursing staff were
      satisfied with the intervention and provided recommendations for adjustments to
      the content of the three components. The most important adjustment is the use of
      video observations to create awareness of nursing staff behaviour. CONCLUSIONS:
      DAIly NURSE, consisting of education, coaching-on-the-job and policy, is feasible
      in nursing home practice. RELEVANCE TO CLINICAL PRACTICE: DAIly NURSE might help
      to change nursing behaviour towards encouraging residents' daily activities and
      independence.

PMID- 30230070
TI  - A Diarylethene-Based Photoswitch and its Photomodulation of the Fluorescence of
      Conjugated Polymers.
AB  - Photochromic diarylethene derivatives, which can reversibly switch the
      fluorescence of adjacent fluorophores between the ON and OFF states under light
      irradiation, have been widely used to construct photoswitchable materials.
      Herein, eight dithienylethene (DTE) groups are integrated onto one polyhedral
      oligomeric silsesquioxane (POSS) core, obtaining a novel super molecular
      photoswitch. After being doped into conjugated polymer nanoparticles, the POSS
      DTE8 molecules show a higher contrast on/off photoswitching performance and a
      quicker responsive speed than free DTE molecules at same molar concentration of
      photochromic units. This enhanced photoswitching efficiency is attributed to the
      increased molecular interaction of the ring-open form and lowered energy of the
      ring-closed form of the DTE units on the POSS core, which is beneficial for the
      ring-closing reaction and subsequent energy transfer between photoswitch and
      fluorophores. In addition, POSS-DTE8 also exhibits good photomodulation behavior
      in the conjugated polymer film, giving it potential applications in optical
      devices.

PMID- 30230071
TI  - Long-Persistent Circularly Polarized Phosphorescence from Chiral Organic Ionic
      Crystals.
AB  - Long-persistent circularly polarized phosphorescence (LPCPP) is achieved for the
      first time in chiral organic ionic crystals at room temperature. The co-crystal
      composed of terephtalic acid (TPA) and chiral alpha-phenylethyamines (PEAs) gave
      rise to LPCPP with lifetimes up to 862 ms and large dissymmetric factor (glum ).
      The hybridization of TPA with chiral PEAs allows circular polarization of the
      generated long-persistent phosphorescence. The observed mirror-image twisted
      molecular structures in the rigid lattices were responsible for the chiroptical
      activation of the generated long-persistent phosphorescence.

PMID- 30230072
TI  - Enterovirus infection during pregnancy is inversely associated with atopic
      disease in the offspring.
AB  - BACKGROUND: Prenatal environment has been shown to influence child's risk of
      atopic diseases. Laboratory-confirmed data about the role of maternal infections
      during pregnancy is scarce. OBJECTIVE: The aim of this study was to determine the
      associations between serologically confirmed maternal infections during pregnancy
      and atopic disease in the offspring. METHODS: This was a nested case-control
      study within a prospective birth cohort study. Altogether 202 atopic case
      children and 333 matched non-atopic control children were included. Atopic
      outcome was defined as having an atopic disease and IgE sensitization by the age
      of 5 years. We analysed serologically acute enterovirus (EV), influenza virus A
      (IAV) and Mycoplasma pneumoniae (M. pneumoniae) infections during pregnancy, and
      mother's seropositivity against human cytomegalovirus (CMV) and Helicobacter
      pylori. RESULTS: Maternal EV infection during pregnancy was inversely associated
      with atopic outcome in the offspring (odds ratio 0.43; 95% confidence interval:
      0.23-0.80, P = 0.008). Acute IAV or M. pneumoniae infections or seropositivity
      against CMV or Helicobacter pylori were not associated with the atopic outcome.
      CONCLUSIONS AND CLINICAL RELEVANCE: Our results suggest that maternal EV
      infections during pregnancy are inversely associated with atopic disease in the
      offspring. Our finding provides further support to the previous studies
      suggesting an important role of the in utero environment in the development of
      atopic diseases.

PMID- 30230073
TI  - Assessing changes in arthropod predator-prey interactions through DNA-based gut
      content analysis-variable environment, stable diet.
AB  - Analysing the structure and dynamics of biotic interaction networks and the
      processes shaping them is currently one of the key fields in ecology. In this
      paper, we develop a novel approach to gut content analysis, thereby deriving a
      new perspective on community interactions and their responses to environment. For
      this, we use an elevational gradient in the High Arctic, asking how the
      environment and species traits interact in shaping predator-prey interactions
      involving the wolf spider Pardosa glacialis. To characterize the community of
      potential prey available to this predator, we used pitfall trapping and vacuum
      sampling. To characterize the prey actually consumed, we applied molecular gut
      content analysis. Using joint species distribution models, we found elevation and
      vegetation mass to explain the most variance in the composition of the prey
      community locally available. However, such environmental variables had only a
      small effect on the prey community found in the spider's gut. These observations
      indicate that Pardosa exerts selective feeding on particular taxa irrespective of
      environmental constraints. By directly modelling the probability of predation
      based on gut content data, we found that neither trait matching in terms of
      predator and prey body size nor phylogenetic or environmental constraints
      modified interaction probability. Our results indicate that taxonomic identity
      may be more important for predator-prey interactions than environmental
      constraints or prey traits. The impact of environmental change on predator-prey
      interactions thus appears to be indirect and mediated by its imprint on the
      community of available prey.

PMID- 30230074
TI  - Five-year experience with pulmonary vein isolation using the second-generation
      cryoballoon for treatment of persistent atrial fibrillation.
AB  - INTRODUCTION: We analyzed the procedural experience and clinical outcome after
      pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation
      (AF) gained over 5 years using the second-generation cryoballoon (CB-Adv).
      METHODS AND RESULTS: For this retrospective study, we enrolled 281 patients
      undergoing PVI at our institution between 2012 and 2016. The analyzed period was
      divided into 5 calendar years. Follow-up data, including Holter
      electrocardiography recordings, were collected during outpatient clinic visits.
      The impact of several variables on outcome was evaluated by means of univariate
      and multivariate analyses and Cox proportional hazards regression models. The
      median procedure and fluoroscopy times over the years were 90 (72 of 114) and 15
      (11 of 21) minutes, respectively. A continuous decline in complication rates and
      fluoroscopy and procedure times was observed in each subsequent year. During mid
      term follow-up (33 [25 of 48] months), 178 (63.3%) patients were AF, atrial
      flutter, or atrial tachycardia free. Multivariate analysis revealed left atrial
      area (hazard ratio [HR] = 1.05; P < 0.001), female sex (HR = 2.53; P < 0.001),
      and common ostium (HR = 1.93; P < 0.001) as significant predictors of outcome.
      The overall 1-year success rate was 76.2%. A gradual decrease in the 1-year
      success rate (from 90.5% in 2012 to 67.9% in 2016) was mainly related to a steady
      increase of left atrial area in the entire cohort with successive years of the
      study. CONCLUSIONS: PVI using CB-Adv in patients with persistent AF is
      accompanied by a learning curve and facilitates a satisfactory outcome, followed
      by the proper selection of patients.

PMID- 30230075
TI  - Metal-Organic Framework Templated 3D Hierarchical ZnCo2 O4 @Ni(OH)2 Core-Shell
      Nanosheet Arrays for High-Performance Supercapacitors.
AB  - Designing core-shell electrode materials with desired components and
      architectures is a promising strategy for boosting electrochemical performance.
      Here, three-dimensional hierarchical ZnCo2 O4 @Ni(OH)2 core-shell nanosheet
      arrays have been successfully fabricated on a Ni foam substrate, in which the
      porous ZnCo2 O4 nanosheet "core" as the conductive scaffold was synthesized by a
      metal-organic framework (MOF)-templated method, and the ultrathin Ni(OH)2
      nanoflakes "shell" with rich active sites were grafted on the ZnCo2 O4 nanosheet
      through a hydrothermal treatment. When directly used as a free-standing electrode
      for supercapacitor, these hierarchical ZnCo2 O4 @Ni(OH)2 core-shell nanosheet
      arrays exhibited a high capacitance of 3063.2 mF cm-2 (1021.1 F g-1 ) at the
      current density of 1 mA cm-2 . This electrode significantly outperformed
      individual Ni(OH)2 or ZnCo2 O4 nanosheet arrays, benefiting from the robust core
      shell arrays on Ni foam with good electrical conductivity and abundant active
      sites, as well as the synergetic effect between MOF-derived porous ZnCo2 O4
      "core" and the ultrathin Ni(OH)2 "shell". Moreover, the assembled ZnCo2 O4
      @Ni(OH)2 //activated-carbon asymmetric supercapacitor displayed excellent energy
      and power densities (maximum of 40.0 Wh kg-1 and 8.02 kW kg-1 ) and superior
      cycling stability of 98.4 % retention with 91.2 % coulombic efficiency over 5 000
      cycles at 10 A g-1 .

PMID- 30230076
TI  - The adaptive significance of chromosomal inversion polymorphisms in Drosophila
      melanogaster.
AB  - Chromosomal inversions, structural mutations that reverse a segment of a
      chromosome, cause suppression of recombination in the heterozygous state. Several
      studies have shown that inversion polymorphisms can form clines or fluctuate
      predictably in frequency over seasonal time spans. These observations prompted
      the hypothesis that chromosomal rearrangements might be subject to spatially
      and/or temporally varying selection. Here, we review what has been learned about
      the adaptive significance of inversion polymorphisms in the vinegar fly
      Drosophila melanogaster, the species in which they were first discovered by
      Sturtevant in 1917. A large body of work provides compelling evidence that
      several inversions in this system are adaptive; however, the precise selective
      mechanisms that maintain them polymorphic in natural populations remain poorly
      understood. Recent advances in population genomics, modelling and functional
      genetics promise to greatly improve our understanding of this long-standing and
      fundamental problem in the near future.

PMID- 30230077
TI  - Effects of two translated phrases of distress thermometer on screening distress
      in Chinese cancer patients: A comparative study.
AB  - AIMS AND OBJECTIVES: To compare the screening effectiveness of two translated
      phrases of the Distress Thermometer (DT), namely the XinLiTongKu Thermometer (DT
      X) and KunRao Thermometer (DT-K), in Chinese patients with cancer. BACKGROUND:
      The DT is one of the most commonly used tools to screen cancer patients'
      psychological states. However, translations of the DT are not uniform in China;
      this may affect the screening effectiveness of this tool. DESIGN: Cross-sectional
      survey with randomisation and self-control. METHODS: A sample of 172 cases was
      screened using the two DT translations, to check and compare the screening
      effectiveness of the two translations. The correlation between them was also
      investigated. The causes of the differences in screening effectiveness of the two
      translations were analysed, using 90 of the above 172 cases and an additional 68
      cases. STROBE guidelines were used in reporting this study. RESULTS: For the DT-X
      (using a cut-off score of 4), the sensitivity value was 0.82 and the specificity
      value was 0.95, where for the DT-K (using a cut-off score of 3), the values were
      0.78 and 0.79, respectively. The area under the receiver operating characteristic
      curve (AUC) was 0.914 and 0.797, respectively. Scores of the DT-X and the DT-K
      were positively correlated. In concepts of the participants, for both phrases,
      the sequences of the first three meanings were the same-worried, anxious and
      tired-while the fourth to sixth meanings were differed between phrases.
      CONCLUSION: The DT-X and DT-K were both effective screening tools. However, in
      this study, the DT-X had a larger AUC than the DT-K. RELEVANCE TO CLINICAL
      PRACTICE: This study may be useful for enabling better measurement of distress in
      Chinese patients and improving the indigenisation of the DT.

PMID- 30230078
TI  - Everyday life and mastocytosis from a patient perspective-a qualitative study.
AB  - AIM: To investigate and gain knowledge about patients' perspectives on everyday
      life with mastocytosis and how they experience, understand and manage symptoms
      and challenges. BACKGROUND: Indolent systemic mastocytosis (ISM) is a disease
      characterised by the accumulation and activation of mast cells. Symptoms are
      diverse and range from mild to severely debilitating or even fatal. It is
      considered rare but is underdiagnosed due to lack of awareness. Quantitative
      studies have shown that ISM can negatively impact quality of life. No qualitative
      studies have described everyday life with the disease. DESIGN: A qualitative
      interview study taking a phenomenological approach. METHODS: Seven qualitative,
      semi-structured interviews with adult patients with ISM. The analysis was
      inspired by Giorgi's phenomenological method. COREQ reporting guidelines were
      used. RESULTS: Three themes and five subthemes emerged from the analysis. (a) The
      everyday life with a rare disease, unknown to most people. Being perceived as a
      hypochondriac in the encounter with the health system. The diagnosis makes a
      difference. Expert knowledge is important. (b) Living with and handling the
      invisible and visible symptoms. The visible body. (c) Fearing an attack. Feeling
      safe and vulnerable at the same time. CONCLUSION: Patients with ISM are severely
      affected in their everyday lives, especially in terms of their relationship with
      family and social network. Symptoms restrict and complicate activities and
      participation in social contexts, and the fear of an anaphylactic attack is
      always present. The disease affects patients' self-perception and sexuality. The
      rarity of the disease and general low awareness seems to be of great importance
      in the encounter with the healthcare system, both before and after diagnosis, and
      there is a need for expert knowledge, support and care. RELEVANCE FOR CLINICAL
      PRACTICE: The focus of counselling should not only be on the disease itself, but
      also on living life with the disease.

PMID- 30230079
TI  - Characterization and significance of localized sources identified by a novel
      automated algorithm during mapping of human persistent atrial fibrillation.
AB  - BACKGROUND: Automated algorithms may identify focal (FA) and rotational (RoA)
      activations during persistent atrial fibrillation (PeAF). OBJECTIVE: To evaluate
      an automated algorithm for characterizing and assessing significance of FA/RoA.
      METHODS: Eighty-six PeAF ablation patients (1411 maps) were analyzed. Maps were
      obtained with a 64-electrode basket using CARTOFINDER, which filters/annotates
      atrial unipolar electrograms over 30 seconds. Operators ablated FA/RoA followed
      by pulmonary vein isolation (PVI). The automated algorithm was retrospectively
      applied using QS patterns to identify FA and sequential activation gradients for
      RoA without phase mapping. Algorithm-identified FA and RoA were validated against
      blinded adjudicators. Ablation of algorithm-identified FA/RoA was related to
      procedural AF termination. RESULTS: 73% +/- 18% of electrodes (65% +/- 11% atrial
      surface area) were adequate for analysis. Compared with adjudicators, the
      algorithm had a sensitivity of 84% for FA and 86% for RoA. There were 4 +/- 2 FA
      and 2 +/- 2 RoA per patient. FA occurred 8 +/- 6 times during the 30-second
      window (cumulative duration 8 +/- 6 seconds). RoA occurred 5 +/- 3 times (median
      2, consecutive rotations) with a cumulative duration of 3 +/- 2 seconds. Compared
      to patients without procedural AF termination, patients with termination had more
      FA ablated (75% vs 38%, P = 0.006). AF termination was not predicted by
      percentage of RoA ablated although there was a trend towards a higher percentage
      of left atrial RoA ablated ( P = 0.06). CONCLUSION: An automated algorithm had
      high sensitivity for FA and RoA. Acute AF termination was associated with FA
      ablation but not RoA ablation. Future studies need to define the significance of
      FA and RoA and whether they are overlapping or separate mechanisms.

PMID- 30230080
TI  - The function of spineless in antenna and wing development of the brown
      planthopper, Nilaparvata lugens.
AB  - A wide array of sensilla are distributed on insect antennae, and they play a
      variety of important roles. Rice planthoppers, destructive pests on rice, have a
      unique antenna sensilla structure called the 'sensory plaque organ'. The
      spineless (ss) gene encodes a bHLH-PAS transcription factor and plays a key role
      in antenna development. In the current study, a 3029 bp full-length cDNA of the
      Nilaparvata lugens ss gene (Nlss) was cloned, and it encodes 654 amino acid
      residues. The highest level of Nlss expression was detected in the thorax of
      fourth-instar nymphs. Knockdown of Nlss in nymphs led to a decrease in the number
      and size of plaque organs. Moreover, the flagella of the treated insects were
      poorly developed, wilted, and even dropped off from the pedicel. Nlss-knockdown
      also resulted in twisted wings in both long-winged and short-winged brown
      planthoppers. Y-type olfactometer analyses indicated that antenna defects
      originating from Nlss depletion resulted in less sensitivity to host volatiles.
      This study represents the first report of the characteristics and functions of
      Nlss in N. lugens antenna and wing development and illuminates the function of
      the plaque organ of N. lugens in host volatile perception.

PMID- 30230082
TI  - Estimating selection on the act of inbreeding in a population with strong
      inbreeding depression.
AB  - Inbreeding depression is widely regarded as a driving force in the evolution of
      dispersal, mate choice and sperm selection. However, due to likely costs of
      inbreeding avoidance, which are poorly understood, it is unclear to what extent
      selection to avoid inbreeding is expected in nature. Moreover, there are
      currently very few empirical estimates of the strength of selection against the
      act of inbreeding (mating with a relative), as opposed to the fitness costs of
      being inbred. Here, we use data from the individual-based study of red deer on
      the Scottish island of Rum, a strongly polygynous system which harbours a large
      inbreeding load, to estimate selection against the act of inbreeding for each
      sex. We use pedigree and genomic estimates of relatedness between individuals and
      measure fitness using both lifetime breeding success (number of calves born) and
      lifetime reproductive success (number of calves surviving to independence), with
      the latter incorporating inbreeding depression in calf survival. We find for both
      sexes that the repeatability of the act of inbreeding was low (< 0.1), suggesting
      little among-individual variation for this trait on which selection can act.
      Using the genomic measures, there was significant selection against the act of
      inbreeding in males, but not in females, and there was considerable uncertainty
      in the estimate in both sexes. We discuss possible explanations for these
      patterns and their implications for understanding the evolution of inbreeding
      avoidance in natural populations.

PMID- 30230081
TI  - Lineage-specific duplication and adaptive evolution of bitter taste receptor
      genes in bats.
AB  - By generating raw genetic material and diverse biological functions, gene
      duplication represents a major evolutionary mechanism that is of fundamental
      importance in ecological adaptation. The lineage-specific duplication events of
      bitter taste receptor genes (Tas2rs) have been identified in a number of
      vertebrates, but functional evolution of new Tas2r copies after duplication
      remains largely unknown. Here, we present the largest data set of bat Tas2rs to
      date, identified from existing genome sequences of 15 bat species and newly
      sequenced from 17 bat species, and demonstrate lineage-specific duplications of
      Tas2r16, Tas2r18 and Tas2r41 that only occurred in Myotis bats. Myotis bats are
      highly speciose and represent the only mammalian genus that is naturally
      distributed on every continent except Antarctica. The occupation of such diverse
      habitats might have driven the Tas2r gene expansion. New copies of Tas2rs in
      Myotis bats have shown molecular adaptation and functional divergence. For
      example, three copies of Tas2r16 in Myotis davidii showed differential
      sensitivities to arbutin and salicin that may occur in their insect prey, as
      suggested by cell-based functional assays. We hypothesize that functional
      differences among Tas2r copies in Myotis bats would increase their survival rate
      through preventing the ingestion of an elevated number of bitter-tasting dietary
      toxins from their insect prey, which may have facilitated their adaptation to
      diverse habitats. Our study demonstrates functional changes of new Tas2r copies
      after lineage-specific duplications in Myotis bats and highlights the potential
      role of taste perception in exploiting new environments.

PMID- 30230083
TI  - Nursing handover of vital signs at the transition of care from the emergency
      department to the inpatient ward: An integrative review.
AB  - AIM: To examine nursing handover of vital signs during patient care transition
      from the emergency department (ED) to inpatient wards. BACKGROUND: Communication
      failures are a leading cause of patient harm making communication through
      clinical handover an international healthcare priority. The transition of care
      from ED to ward settings is informed by nursing handover. Vital sign
      abnormalities in the ED are associated with clinical deterioration following
      hospital admission. Understanding the role and perceived value of vital sign
      content in clinical handover is important for patient safety. METHODS: An
      integrative design was used. A search of electronic databases was undertaken
      using MEDLINE, CINAHL, EMBASE, Cochrane, Web of Science and SCOPUS. Identified
      records were screened to elicit further studies for inclusion. A comprehensive
      peer-review screening process was performed. Studies were included that described
      the surrounding issues of handover, vital signs, ED, transition of care and ward.
      RESULTS: Five studies were included in the final review, one specific to nursing
      and four specific to emergency medicine. Vital signs were perceived to be an
      important inclusion in clinical handover, and the communication of vital signs in
      handover was perceived to be indicators for patient safety and risk factors for
      future clinical deterioration. The ED environment had an influence on effective
      communication within handover. CONCLUSIONS: Vital signs were an important
      inclusion for clinical handover. Deficiencies in vital sign content were
      perceived to be risk factors for patient adverse events following hospital
      admission. The quality of vital sign information in clinical handover may be
      important for accurate decision-making. RELEVANCE TO CLINICAL PRACTICE: Vital
      signs are an important component of clinical handover and are perceived to be
      indicators for patient safety and risk of future adverse events.

PMID- 30230084
TI  - Commentary on Livingston et al. (2018): Change in gender ratios, what do they
      signify?

PMID- 30230085
TI  - Demonstration of pulmonary vein exit block following pulmonary vein isolation: A
      novel use for adenosine.
AB  - INTRODUCTION: Demonstration of exit block after pulmonary vein isolation (PVI) is
      the cornerstone of ablation for atrial fibrillation (AF). It requires the
      demonstration of local pulmonary vein (PV) capture and absence of conduction to
      the atrium but is often challenging due to the inability to see local paced PV
      evoked potentials. We retrospectively examined the ability of adenosine to
      augment this technique during CARTO-based radiofrequency ablation procedures.
      METHODS: Retrospective analysis of evoked PV potentials during adenosine
      administration while testing for PV exit block at a single UK center. RESULTS:
      One hundred and twenty-nine PVs in 33 patients were isolated using radiofrequency
      energy to demonstrate entry block. Of those, the pacing of 24 veins under
      baseline conditions did not clearly demonstrate local PV-evoked potentials
      sufficient to be sure that the local vein was truly captured and dissociated from
      the atrium. Adenosine was administered in 19 of these, with 10 of 19 (52.6%)
      veins then demonstrating clear local PV-evoked potentials transiently during
      adenosine administration, sufficient to allow assessment of definite exit block.
      CONCLUSION: Adenosine administered during PV pacing allows transient
      visualization of local PV-evoked potentials after PVI facilitating the clearer
      demonstration of PV exit block in over 50% veins.

PMID- 30230086
TI  - Next generation sequencing of the cellular and liquid fraction of pancreatic cyst
      fluid supports discrimination of IPMN from pseudocysts and reveals cases with
      multiple mutated driver clones: First findings from the prospective ZYSTEUS
      biomarker study.
AB  - Approximately half of all pancreatic cysts are neoplastic, mainly comprising
      intraductal papillary mucinous neoplasms (IPMN), which can progress to invasive
      carcinoma. Current Fukuoka guidelines have limited sensitivity and specificity in
      predicting progression of asymptomatic pancreatic cysts. We present first results
      of the prospective ZYSTEUS biomarker study investigating (i) whether detection of
      driver mutations in IPMN by liquid biopsy is technically feasible, (ii) which
      compartment of IPMN is most suitable for analysis, and (iii) implications for
      clinical diagnostics. Twenty-two patients with clinical inclusion criteria were
      enrolled in ZYSTEUS. Fifteen cases underwent endoscopic ultrasound (EUS)-guided
      fine-needle aspiration and cytological diagnostics. Cellular and liquid fraction
      of the cysts of each case were separated and subjected to deep targeted next
      generation sequencing (NGS). Clinical parameters, imaging findings (EUS and MRI),
      and follow-up data were collected continuously. All IPMN cases (n = 12) showed at
      least one mutation in either KRAS (n = 11) or GNAS (n = 4). Three cases showed
      both KRAS and GNAS mutations. Six cases harbored multiple KRAS/GNAS mutations. In
      the three cases with pseudocysts, no KRAS or GNAS mutations were detected. DNA
      yields were higher and showed higher mutation diversity in the cellular fraction.
      In conclusion, mutation detection in pancreatic cyst fluid is technically
      feasible with more robust results in the cellular than in the liquid fraction.
      Current results suggest that, together with imaging, targeted sequencing supports
      discrimination of IPMN from pseudocysts. The prospective design of ZYSTEUS will
      provide insight into diagnostic value of NGS in preoperative risk stratification.
      Our data provide evidence for an oligoclonal nature of IPMN.

PMID- 30230087
TI  - Changing from 12-hr to 8-hr day shifts: A qualitative exploration of effects on
      organising nursing care and staffing.
AB  - AIMS AND OBJECTIVES: To investigate (a) How nursing care is organised on wards
      where nursing staff work different lengths of day shifts, and (b) How length of
      day shift affects the staffing of wards. BACKGROUND: Twelve-hour shifts have
      become increasingly common worldwide but there are concerns about impact on care
      quality and safety. Eight-hour shifts, and how day shift length affects how
      nurses organise their work, and staffing, have been little studied. DESIGN: Case
      study. METHODS: The setting was two older people's wards in an acute hospital in
      England. Nursing staff on one ward continued to work 12-hr day shifts; staff on
      the other ward worked 8 hr late and early day shifts, with an afternoon overlap,
      for 6 months. Qualitative interviews were conducted with 22 nursing staff. Semi
      structured observations were conducted from 12-15.00 (5 * 3 hr episodes on each
      ward). Data analysis was conducted using the Framework approach. RESULTS: Theme
      1: Organising nursing care and staff activities, (sub-themes: Care delivery
      across a 12 hr shift; Care delivery on early and late 8 hr shifts; Staff
      communication and documentation; Staff breaks; Teaching, supervision and staff
      development); Theme 2: Staffing wards with different length of day shift (sub
      themes:: Adequacy of staffing and use of temporary staff; Recruitment and
      retention of staff after introducing 8 hr shifts). CONCLUSION: Nursing staff
      organised care on 8-hr shifts similarly to 12-hr shifts but then felt
      dissatisfied with their care delivery and handovers. Nursing staff on both wards
      approached care in a task-focused way. There were concerns that adopting an 8-hr
      shift pattern negatively affected recruitment and retention. RELEVANCE TO
      CLINICAL PRACTICE: Changing from 12 hr to 8 hr day shifts may affect nursing
      staff satisfaction with their care delivery and handovers, and have a negative
      effect on staffing wards.

PMID- 30230088
TI  - The importance of extrapulmonary vein triggers and atypical atrial flutter in
      atrial fibrillation recurrence after cryoablation: Insights from repeat ablation
      procedures.
AB  - INTRODUCTION: It has not been previously investigated whether the recurrence
      mechanism after cryoballoon ablation (CBA) of paroxysmal atrial fibrillation (AF)
      is similar to that of radiofrequency catheter ablation (RFCA). We aimed to
      evaluate the differences of recurrence characteristics between RFCA and CBA after
      the index procedure. METHODS: A total of 210 patients were enrolled in the study,
      and 69 patients underwent pulmonary vein (PV) isolation using a 28-mm second
      generation CBA. The control group comprising 140 patients underwent PV isolation
      using an open-irrigated radiofrequency ablation catheter. A total of 69 patients
      in the CBA group and 69 patients in the RFCA group were investigated after
      propensity score matching. Recurrence patterns of AF were studied in the repeated
      procedure. RESULTS: During the index procedure, there was no difference in PV or
      non-PV triggers between the two groups. Nineteen (27.5%) patients in the CBA
      group and 19 (27.5%) patients in the RFCA group had recurrence after a follow-up
      of 11.3 +/- 7 months. The Kaplan-Meier curve did not reveal significant
      difference in recurrence (log-rank, P = 0.364) between the two groups. In the
      second procedure, the CBA group had more non-PV triggers (63.6%, P = 0.009) and
      left atrial (LA) flutters (54.5%, P = 0.027) compared with the RFCA group (12.5%
      and 12.5%, respectively). The PV reconnection rates were similar between both
      groups. CONCLUSIONS: There was no difference in AF recurrence after catheter
      ablation between CBA and RFCA, but significant increases of non-PV triggers and
      LA flutter during the second procedure suggest the importance of the atrial
      substrate in maintaining AF during the second procedure after previous CBA.

PMID- 30230090
TI  - The matrix-assisted laser desorption/ionisation in-source decay of peptides using
      ion mobility enabled quadrupole-time-of-flight mass spectrometry.
AB  - RATIONALE: In-source decay (ISD) matrix-assisted laser desorption/ionisation
      (MALDI) mass spectrometry with a 1,5-diaminonaphthalene (1,5-DAN) matrix is used
      for the structural characterisation of peptides. However, MALDI spectra are
      intrinsically complicated by the presence of matrix ions, which interfere with
      the peptide fragments. This may cause false-positive results or reduced sequence
      coverage. This paper reports investigations of ISD processes in an intermediate
      pressure MALDI ion source and a protocol for the removal of interfering ions
      using ion mobility separation (IMS). METHODS: An intermediate pressure MALDI
      source of a Q-IMS-Q-TOF instrument (Synapt G2) has been employed for the ISD of
      selected peptides using a 1,5-DAN matrix. RESULTS: Successful coupling of the
      MALDI source tuned for ISD experiments using IMS is demonstrated. The IMS made it
      possible to remove interfering matrix ions effectively from the spectra and thus
      to increase the confidence of spectral interpretation. Extensive fragment series
      corresponding to N-Calpha bond cleavages were observed under optimised
      conditions; on the other hand, weaker series of ions caused by peptide bond
      cleavages were prevalent for default conditions and/or the alpha-hydroxycinnamic
      acid matrix. CONCLUSIONS: Ion mobility has been used for the elimination of
      matrix ions. The technique has been applied to top-down sequencing of non-tryptic
      peptides, such as the human palmitoylated analogue of prolactin-releasing peptide
      used in recent obesity studies, and human and insect antimicrobial peptides.

PMID- 30230091
TI  - CT Reconstruction Levels Affect Automated and Reader-Based ASPECTS Ratings in
      Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: We investigated whether automated and reader-based
      ASPECTS in acute stroke patients are affected by different CT image
      reconstruction algorithms. METHODS: ASPECTS were assessed by commercial software
      and four independent blinded readers (two residents and two consultants) from
      different CT reconstructions (filtered back projection and two different
      iterative reconstruction [IR] levels) in 43 acute stroke patients with proximal
      middle cerebral artery occlusion. Ground truth was provided by an expert with
      unrestricted data access. RESULTS: The residents showed significant variations
      between IR levels and had a significantly lower internal consistency across
      different reconstructions compared to the software, which performed similarly to
      the consultants. The consultant as well as the software also showed different
      deviations from ground truth with different IR levels, which were least at IR
      strength level 2. CONCLUSIONS: CT image postprocessing affects either automated
      or human ASPECTS in acute stroke patients. This effect was most pronounced in the
      less experienced readers, while the software had the most robust performance.

PMID- 30230089
TI  - Inorganic polyphosphate interacts with nucleolar and glycosomal proteins in
      trypanosomatids.
AB  - Inorganic polyphosphate (polyP) is a polymer of three to hundreds of phosphate
      units bound by high-energy phosphoanhydride bonds and present from bacteria to
      humans. Most polyP in trypanosomatids is concentrated in acidocalcisomes, acidic
      calcium stores that possess a number of pumps, exchangers, and channels, and are
      important for their survival. In this work, using polyP as bait we identified >
      25 putative protein targets in cell lysates of both Trypanosoma cruzi and
      Trypanosoma brucei. Gene ontology analysis of the binding partners found a
      significant over-representation of nucleolar and glycosomal proteins. Using the
      polyphosphate-binding domain (PPBD) of Escherichia coli exopolyphosphatase (PPX),
      we localized long-chain polyP to the nucleoli and glycosomes of trypanosomes. A
      competitive assay based on the pre-incubation of PPBD with exogenous polyP and
      subsequent immunofluorescence assay of procyclic forms (PCF) of T. brucei showed
      polyP concentration-dependent and chain length-dependent decrease in the
      fluorescence signal. Subcellular fractionation experiments confirmed the presence
      of polyP in glycosomes of T. brucei PCF. Targeting of yeast PPX to the glycosomes
      of PCF resulted in polyP hydrolysis, alteration in their glycolytic flux and
      increase in their susceptibility to oxidative stress.

PMID- 30230092
TI  - Sex chromosome inversions enforce reproductive isolation across an avian hybrid
      zone.
AB  - Across hybrid zones, the sex chromosomes are often more strongly differentiated
      than the autosomes. This is regularly attributed to the greater frequency of
      reproductive incompatibilities accumulating on sex chromosomes and their exposure
      in the heterogametic sex. Working within an avian hybrid zone, we explore the
      possibility that chromosome inversions differentially accumulate on the Z
      chromosome compared to the autosomes and thereby contribute to Z chromosome
      differentiation. We analyse the northern Australian hybrid zone between two
      subspecies of the long-tailed finch (Poephila acuticauda), first described based
      on differences in bill colour, using reduced-representation genomic sequencing
      for 293 individuals over a 1,530-km transect. Autosomal differentiation between
      subspecies is minimal. In contrast, 75% of the Z chromosome is highly
      differentiated and shows a steep genomic cline, which is displaced 350 km to the
      west of the cline in bill colour. Differentiation is associated with two or more
      putative chromosomal inversions, each predominating in one subspecies. If
      inversions reduce recombination between hybrid incompatibilities, they are
      selectively favoured and should therefore accumulate in hybrid zones. We argue
      that this predisposes inversions to differentially accumulate on the Z
      chromosome. One genomic region affecting bill colour is on the Z, but the main
      candidates are on chromosome 8. This and the displacement of the bill colour and
      Z chromosome cline centres suggest that bill colour has not strongly contributed
      to inversion accumulation. Based on cline width, however, the Z chromosome and
      bill colour both contribute to reproductive isolation established between this
      pair of subspecies.

PMID- 30230093
TI  - Baseline ASPECTS and e-ASPECTS Correlation with Infarct Volume and Functional
      Outcome in Patients Undergoing Mechanical Thrombectomy.
AB  - BACKGROUND AND PURPOSE: The role of Alberta Stroke Program Early CT score
      (ASPECTS) in predicting which patients are likely to benefit from endovascular
      therapy (EVT) is not well defined. An automated software (e-ASPECTS) has been
      created to solve its poor interrater reliability. We aim to evaluate correlation
      between radiologist (Rx) and e-ASPECTS scoring with cerebral blood volume (CBV)
      infarct core and with final infarct volume; as well as with long-term functional
      outcome. METHODS: We included patients with acute ischemic stroke and large
      vessel occlusion who underwent EVT. We measured baseline radiologist (Rx) ASPECTS
      and e-ASPECTS, and baseline CBV infarct core on CT perfusion. Final infarct
      volume was measured on 24-hour control CT. RESULTS: We included 184 patients, in
      which 82.1% of patients achieved complete recanalization. Median Rx-ASPECTS/e
      ASPECTS was 9 (IQR 8-10 vs. IQR 7.75-10) and mean CBV lesion was 29.51 (+/-47.41)
      mL. Correlation (rs ) between ASPECTS and e-ASPECTS was .44 (P < .01). Both
      ASPECTS scores correlated with CBV after 180 minutes of symptom onset (rs = -.41
      vs. -.54, P < .01) and with final infarct volume in patients with complete
      recanalization (rs = -.40 vs. -.43, P < .01). In a logistic regression, either Rx
      ASPECTS, e-ASPECTS, and CBV (OR 1.60 vs. 1.87 vs. .96; P < .05) predicted a low
      infarct volume. Rx-ASPECTS and e-ASPECTS also predicted functional independence
      (mRS 0-2) at 3 months (1.52 vs. 1.37; P < .05). CONCLUSION: ASPECTS and e-ASPECTS
      showed a mild correlation with CBV. Rx-ASPECTS, e-ASPECTS, and CBV predicted a
      low infarct volume after thrombectomy in recanalized patients but only Rx-ASPECTS
      and e-ASPECTS predicted functional independence at 3 months.

PMID- 30230094
TI  - Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: An
      interobserver study of key cytomorphological features from a large academic
      medical centre.
AB  - OBJECTIVE: Because of the indolent nature of noninvasive follicular thyroid
      neoplasm with papillary-like nuclear features (NIFTP) and potential requisite for
      a more conservative treatment, it is crucial to identify features of this entity
      preoperatively. Our group recently published findings that there are several
      cytomorphological features that may be used as clues to distinguish NIFTP,
      papillary thyroid carcinoma (PTC) and follicular adenoma (FA) on fine needle
      aspiration. Therefore, we aimed to determine the interobserver reproducibility of
      these findings. METHODS: Presurgical fine-needle aspiration slides from NIFTP (n
      = 30), classic PTC (n = 30) and FA (n = 30) collected from 1/2013-8/2016 were
      reviewed by seven cytopathologists blindly. Presence of selected
      cytomorphological features was recorded and compared to determine percent
      agreement and inter-rater reliability among study cytopathologists using Gwet's
      AC1 statistics. RESULTS: For all the cytomorphological features, the overall
      percent agreement amongst the pathologists ranged between 65.1% and 86.8% (Gwet's
      AC1 0.30-0.80). There was substantial or almost perfect agreement (Gwet's AC1 >
      0.60) in seven cytomorphological features in the classic PTC group, in six
      features in the NIFTP group and in five features in the FA group. There were no
      features with poor agreement (Gwet's AC1 < 0.0). CONCLUSIONS: The current study
      supports the reproducibility of our previous findings. The high level of
      agreement amongst pathologists for these groups, and particularly the NIFTP
      group, supports the notion that when viewed in combination as a cytological
      profile, these cytomorphological features may assist the cytopathologist in
      raising the possibility of NIFTP preoperatively. This can potentially aid
      clinicians in deciding whether more conservative treatment may be appropriate.

PMID- 30230095
TI  - Comparing breast biomarker status between routine immunohistochemistry and FISH
      studies and Oncotype DX testing, a study of 610 cases.
AB  - INTRODUCTION: Oncotype DX (ODX) testing uses reverse transcription polymerase
      chain reaction (RT-PCR) to predict distant recurrence rate of estrogen receptor
      positive (ER+)/HER2-negative (HER2-)/lymph node-negative (LN-) breast cancers.
      ODX also reports the status of breast cancer biomarkers, ER, progesterone
      receptor (PR), and HER2. This study examined the discrepancy rate of breast
      cancer biomarker status as reported by ODX vs routinely used immunohistochemistry
      (IHC) and fluorescence in situ hybridization (FISH) methods. METHODS: A total of
      610 breast cancer cases (609 ER+ and 1 ER-negative (ER-) by IHC) with ODX reports
      were reviewed. ER, PR, and HER2 status from ODX reports were compared with
      results from IHC and FISH studies. RESULTS: There was an overall high concordance
      rate between IHC and ODX for ER expression (603/610 concordant, 98.9%) and
      moderate concordance for PR expression (549/610 concordant, 90%). Of the seven ER
      discrepant cases, six were positive by IHC but negative by ODX. Of the 61 PR
      discrepant cases, 41 were positive by IHC but negative by ODX. Of the 610 cases,
      568 had HER2 results reported by ODX. Five cases were HER2+ by IHC/FISH (0.88%).
      One of these five cases was reported as HER2+, two as HER2-, and two as HER2
      equivocal by ODX. None of the cases that were HER2- or equivocal by IHC/FISH was
      reported as HER2+ by ODX. CONCLUSIONS: There is good concordance between IHC and
      ODX for ER and PR expression, but IHC is more sensitive. The significant
      discordance in HER2+ cases may discourage reporting HER2 status by ODX testing.

PMID- 30230096
TI  - Diffusion Tensor Imaging of the Calf Muscles in Subjects With and Without
      Diabetes Mellitus.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) has been used to characterize calf
      skeletal muscle architecture. PURPOSE: To assess the diffusional properties of
      the calf muscles of subjects with and without diabetes, at rest and during
      isometric plantarflexion exercise. STUDY TYPE: Prospective. SUBJECTS: Twenty-six
      subjects in two groups: 13 healthy and 13 subjects with type 2 diabetes (DM);
      each group consisted of seven females and six males. FIELD STRENGTH/SEQUENCE:
      3T/2D single-shot spin echo planar imaging. ASSESSMENT: Fractional anisotropy
      (FA), mean diffusivity (MD), diffusion eigenvalues, and fiber tracking indices
      were obtained from the medial gastrocnemius (MG), lateral gastrocnemius (LG), and
      soleus (SOL) muscles of the calf at rest and during isometric plantarflexion
      exercise. STATISTICAL TESTS: We used a combination of nonparametric (Wilcoxon)
      and parametric (t-test) statistical assessments. RESULTS: The medial
      gastrocnemius muscle had more indices with significant differences between the
      two groups (six indices with P < 0.05) than did the lateral gastrocnemius (three
      indices with P < 0.05) and soleus muscles (only one index with P < 0.05). While
      the healthy group showed elevated MD values from rest to exercise (MG = 5.83%, LG
      = 13.45%, and SOL = 11.68%), the diabetic MD showed higher increases (MG =
      19.74%, LG = 29.31%, and SOL = 20.84%) that were different between groups (MG: P
      = 0.009, LG: P = 0.037, and SOL: P = 0.049). DATA CONCLUSION: Our results
      indicate considerable diffusional changes between healthy subjects and subjects
      with diabetes at rest and during isometric plantarflexion exercise in the calf
      muscles. The medial gastrocnemius muscle displayed the most diffusion sensitivity
      to diabetes-related microstructural changes. LEVEL OF EVIDENCE: 2 Technical
      Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30230097
TI  - Multiple functions of miR-8-3p in the development and metamorphosis of the red
      flour beetle, Tribolium castaneum.
AB  - The microRNA miR-8-3p is conserved among insects and closely involved in
      development and immunity, but its functions in vivo are unexplored in the red
      flour beetle, Tribolium castaneum. Here, we show that miR-8-3p was highly
      expressed in late larva and early adult stages, as determined by quantitative
      real-time PCR. It was enriched in the fat body and cuticle in late larval tissues
      and abundant in the head and cuticle in early adult tissues, indicating this
      microRNA plays important roles during T. castaneum development. Specific
      inhibition of miR-8-3p in late larvae led to metamorphosis defects in the
      development of wings, eyes, legs and embryo. Moreover, a series of genes related
      to organism development were identified as miR-8-3p targets by computational
      prediction and microRNA-messenger RNA interaction validation, including Wingless,
      Eyg, Fpps and Sema-1a. These genes were critical for the regulation of the larva
      to-adult transition. Eyg, as a functional target of miR-8-3p, participates in eye
      development, which was further confirmed by luciferase assay and loss-of-function
      analyses. In brief, miR-8-3p is broadly involved in the development of wings,
      eyes and legs through its target genes and has extensive regulatory roles during
      T. castaneum development.

PMID- 30230098
TI  - Feasibility of subcutaneous implantable cardioverter-defibrillator implantation
      with opioid sparing truncal plane blocks and deep sedation.
AB  - INTRODUCTION: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is
      most commonly implanted under general anesthesia (GA), due to the intraoperative
      discomfort associated with tunneling and dissection. Postoperative pain can be
      substantial and is often managed with opioids. There is a growing interest in
      transitioning away from the routine use of GA during S-ICD implantation, while
      also controlling perioperative discomfort without the use of narcotics. As such,
      we assessed the feasibility of a multimodal analgesia regimen that included
      regional anesthesia techniques in patients undergoing S-ICD implantation. METHODS
      AND RESULTS: Twenty patients received truncal plane block (TBL) immediately
      before S-ICD implantation. The first 10 patients were implanted under general
      anesthesia (GA + TBL), and the next 10 patients were implanted under deep
      sedation (DS + TBL). Additionally, the DS + TBL patients were also prescribed a
      structured regimen of nonopioid analgesics in the perioperative period. Opioid
      consumption was calculated as milligram morphine equivalents (MME). In-hospital
      opioid consumption was significantly lower in the patients implanted with DS +
      TBL (MME = 0) as compared with patients receiving GA + TBL (MME = 60; P = 0.004).
      CONCLUSIONS: Subcutaneous ICD implantation with anesthesia-delivered DS and a
      multimodal anesthetic regimen that includes TBL is feasible and associated with
      significantly less perioperative opioid consumption.

PMID- 30230099
TI  - Cine MRI assessment of motility in the unprepared small bowel in the fasting and
      fed state: Beyond the breath-hold.
AB  - BACKGROUND: The symptoms of functional bowel disorders are common in postprandial
      but investigations are generally undertaken in the fasted state using invasive
      procedures. MRI provides a noninvasive tool to study the gastrointestinal tract
      in an unperturbed, fed state. The aim of this study was to develop a technique to
      assess small bowel motility from cine MRI data in the unprepared bowel in fasting
      and fed states. METHODS: Fifteen healthy volunteers underwent a baseline MRI scan
      after which they consumed a 400 g soup. Subjects then underwent a postprandial
      scan followed by further scans at regular intervals. Small bowel motility was
      assessed using single-slice bTFE cine MRI. An optimized processing technique was
      used to generate motility data based on power spectrum analysis of voxel-signal
      changes with time. Interobserver variability (n = 15) and intra-observer (n = 6)
      variability were assessed. Changes in the motility index were compared between
      fasted and immediate postprandial state. KEY RESULTS: Excellent agreement between
      observers was seen across the range of motility measurements acquired, with
      intraclass correlation coefficient (ICC) of 0.979 (P < 0.0001) and Bland-Altman
      limits of agreement 95% CI: -28.9 to 45.9 au. Intra-observer variability was low
      with ICC of 0.992 and 0.960 (2 observers, P < 0.0001). Changes from the fasted to
      immediately postprandial state showed an average increase of 122.4% +/- 98.7% (n
      = 15). CONCLUSIONS & INFERENCES: This optimized technique showed excellent inter
      and intra observer agreement. It was sensitive to changes in motility induced
      feeding. This technique will be useful to study contractile activity and regional
      patterns along the gastrointestinal tract under physiological conditions.

PMID- 30230100
TI  - Combined functions of two RRMs in Dead-end1 mimic helicase activity to promote
      nanos1 translation in the germline.
AB  - Dead-end1 (Dnd1) expression is restricted to the vertebrate germline where it is
      believed to activate translation of messenger RNAs (mRNAs) required to protect
      and promote that unique lineage. Nanos1 is one such germline mRNA whose
      translation is blocked by a secondary mRNA structure within the open reading
      frame (ORF). Dnd1 contains a canonical RNA recognition motif (RRM1) in its N
      terminus but also contains a less conserved RRM2. Here we provide a mechanistic
      picture of the nanos1 mRNA-Dnd1 interaction in the Xenopus germline. We show that
      RRM1, but not RRM2, is required for binding nanos1. Similar to the zebrafish
      homolog, Xenopus Dnd1 possesses ATPase activity. Surprisingly, this activity
      appears to be within the RRM2, different from the C-terminal region where it is
      found in zebrafish. More importantly, we show that RRM2 is required for nanos1
      translation and germline survival. Further, Dnd1 functions as a homodimer and
      binds nanos1 mRNA just downstream of the secondary structure required for nanos1
      repression. We propose a model in which the RRM1 is required to bind nanos1 mRNA
      while the RRM2 is required to promote translation through the action of ATPase.
      Dnd1 appears to use RRMs to mimic the function of helicases.

PMID- 30230101
TI  - Outcomes of paroxysmal atrial fibrillation ablation studies are affected more by
      study design and patient mix than ablation technique.
AB  - OBJECTIVE: We tested whether ablation methodology and study design can explain
      the varying outcomes in terms of atrial fibrillation (AF)-free survival at 1
      year. BACKGROUND: There have been numerous paroxysmal AF ablation trials, which
      are heterogeneous in their use of different ablation techniques and study design.
      A useful approach to understanding how these factors influence outcome is to
      dismantle the trials into individual arms and reconstitute them as a large meta
      regression. METHODS: Data were collected from 66 studies (6941 patients). With
      freedom from AF as the dependent variable, we performed meta-regression using the
      individual study arm as the unit. RESULTS: Success rates did not change
      regardless of the technique used to produce pulmonary vein isolation (PVI).
      Neither was adjunctive lesion sets associated with any improvement in outcome.
      Studies that included more males and fewer hypertensive patients were found more
      likely to report better outcomes. The electrocardiography method selected to
      assess outcome also plays an important role. Outcomes were worse in studies that
      used regular telemonitoring (by 23%; P < 0.001) or in patients who had
      implantable loop recorders (by 21%; P = 0.006), rather than those with the less
      thorough periodic Holter monitoring. CONCLUSIONS: Outcomes of AF ablation studies
      involving PVI are not affected by the technologies used to produce PVI. Neither
      do adjunctive lesion sets change the outcome. Achieving high success rates in
      these studies appears to be dependent more on patient mix and on the thoroughness
      of AF detection protocols. These should be carefully considered when quoting the
      success rates of AF ablation procedures that are derived from such studies.

PMID- 30230103
TI  - Mandibular canines with additional roots: An ex vivo study of the external and
      internal morphology.
AB  - The aim of this study was to investigate the root and root canal morphologies of
      mandibular canines with additional roots using cone-beam computed tomography.
      Seventy-seven extracted two-rooted and one-three-rooted permanent human
      mandibular canines were selected. Aspects of the external morphology evaluated
      were crown length, root length, total length, root bifurcation distance from the
      cementoenamel junction, root size, and direction of the root curvature in the
      apical third. Features of internal morphology assessed were root canal number per
      root, root canal bifurcation distance from the cementoenamel junction, and the
      angle between the buccal or lingual canal and the main canal. The root size and
      length presented considerable diversity. Most of the roots bifurcated at the
      middle third and exhibited a buccal curvature. The main root canal bifurcated
      coronally in two root canals, a buccal and a lingual. The majority of the buccal
      and lingual root canal angles were blunt. The presence of a third root in a
      specimen was a novel finding of this study.

PMID- 30230102
TI  - Derealization and self-harm strategies are used to regulate disgust, fear, and
      sadness in adult survivors of childhood sexual abuse.
AB  - Emotion regulation (ER) difficulties have been identified as an important target
      for clinical intervention in the treatment of post-traumatic stress disorder
      (PTSD) symptoms in survivors of childhood sexual abuse (CSA). However, there is
      limited research regarding the use of specific strategies to regulate specific
      emotions following exposure to traumatic events. The aim of the current study was
      to investigate the indirect effects of four trauma-related emotions (anger,
      sadness, disgust, and fear) on PTSD severity via two mediators: derealization and
      self-harm. In particular, we tested that if the two hypothetical mediators
      operate sequentially, derealization precedes self-harm and/or self-harm precedes
      derealization. A predominate female clinical sample (N = 109) of CSA survivors
      completed measures of experience of emotions, ER, and post-traumatic stress.
      Bivariate and serial mediation analyses were conducted to test the direct and
      indirect effects of trauma-related emotions on PTSD severity. Serial mediation
      analyses indicated that there were significant total effects of all trauma
      related emotions on PTSD severity. Three trauma-related emotions (sadness,
      disgust, and fear) were indirectly associated to PTSD severity via derealization
      and self-harm and via self-harm and derealization. Results indicate that
      difficulties in regulating the emotions of sadness, disgust, and fear may result
      in more severe derealization and self-harm as coping strategies, which in turn
      lead to greater PTSD severity. The sequence of mediators does not hold great
      importance in these pathways. Overall, our findings suggest that therapeutically
      targeting derealization and self-harm might enable the reduction of PTSD among
      CSA survivors.

PMID- 30230104
TI  - Sexual Orientation-Based Depression and Suicidality Health Disparities: The
      Protective Role of School-Based Health Centers.
AB  - This study's purpose was to examine whether school-based health centers (SBHCs)
      support mental health indicators among sexual minority youth (SMY). Data came
      from the 2015 Oregon Healthy Teens Survey with 13,608 11th graders in 137 public
      high schools in Oregon. Regression results revealed significant SBHC by SMY
      status interactions indicating relative reductions in likelihood of depressive
      episodes (30%), suicidal ideation (34%), and suicide attempts (43%) among SMY in
      schools with SBHCs. SMY students in SBHC schools reported lower likelihood of a
      past-year depressive episode, suicidal ideation, and suicide attempt versus those
      attending non-SBHC schools. Conversely, no differences in these outcomes were
      observed for non-SMY by SBHC status. SBHCs may help reduce mental health
      disparities among SMY, a marginalized, underserved population.

PMID- 30230105
TI  - Survival of the fastest.

PMID- 30230106
TI  - Lead I R-wave amplitude to differentiate idiopathic ventricular arrhythmias with
      left bundle branch block right inferior axis originating from the left versus
      right ventricular outflow tract.
AB  - INTRODUCTION: Differentiation of right versus left ventricular outflow tract
      (RVOT vs. LVOT) arrhythmia origin with left bundle branch block right inferior
      axis (LBRI) morphology is relevant to ablation planning and risk discussion. Our
      aim was to determine if lead I R-wave amplitude is useful for differentiation of
      RVOT from LVOT arrhythmias with LBRI morphology. METHODS: The R-wave amplitude in
      lead I was measured in a retrospective cohort of 75 consecutive patients with
      LBRI pattern ventricular arrhythmias (VAs) successfully ablated from the RVOT (n
      = 54), LVOT (n = 16), or the anterior interventricular vein (AIV; n = 5). The
      optimal R-wave threshold was identified and diagnostic indices were compared with
      the previously reported transitional zone (TZ) index and V2S/V3R index. RESULTS:
      An R-wave amplitude greater than or equal to 0.1 mV predicted LVOT origin with
      75% sensitivity and 98.2% specificity. In comparison, the TZ and V2S/V3R indices
      had 50% and 68.8% sensitivity, and 75.9% and 88.9% specificity, respectively, for
      predicting LVOT origin. The area under the curve (AUC) was 0.85 for lead I R-wave
      amplitude, 0.87 for V2S/V3R, and 0.72 for the TZ index. Of 36 cases with QS in
      lead I, 30 (83.3%) were from the anterior RVOT, three (8.3%) from the LVOT, and
      three (8.3%) from the AIV. CONCLUSION: The presence of R-wave amplitude in lead I
      (>=0.1 mV) is a simple and useful criterion to identify LVOT cusp or endocardium
      focus in LBRI arrhythmias. A QS pattern in lead I suggests an origin in the
      anterior RVOT, or less commonly the adjacent LV summit.

PMID- 30230107
TI  - Relationship of Seminal Megavesicles, Prostate Median Cysts, and Genotype in
      Autosomal Dominant Polycystic Kidney Disease.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) can involve
      prostate and seminal vesicles but the potential interrelationship of these
      findings and associations with PKD gene mutation locus and type is unknown.
      PURPOSE: To determine the interrelationship of seminal megavesicles (seminal
      vesicles with lumen diameter > 10mm) and prostatic cysts in ADPKD and to
      determine whether there are associations with PKD gene mutations. STUDY TYPE:
      Retrospective, case control. POPULATION: Male ADPKD subjects (n = 92) with
      mutations in PKD1 (n = 71; 77%) or PKD2 (n = 21; 23%), and age/gender-matched
      controls without ADPKD (n = 92). FIELD STRENGTH/SEQUENCE: 1.5T, axial/coronal T2 
      weighted MR images. ASSESSMENT: Reviewers blinded to genotype independently
      measured seminal vesicle lumen diameter and prevalence of cysts in prostate,
      kidney, and liver. STATISTICAL TESTS: Nonparametric tests for group comparisons
      and univariate and multivariable logistic regression analyses to identify
      associations of megavesicles and prostate median cysts with mutations and
      renal/hepatic cyst burden. RESULTS: Seminal megavesicles were found in 23 of 92
      ADPKD (25%) subjects with PKD1 (22/71, 31%) or PKD2 (n = 1/21, 5%) mutations, but
      in only two control subjects (P < 0.0001). Prostate median cysts were found in
      17/92 (18%) ADPKD subjects, compared with only 6/92 (7%) controls (P = 0.01), and
      were correlated with seminal vesicle diameters (rho = 0.24, P = 0.02). Nonmedian
      prostate cyst prevalence was identical between ADPKD and controls (7/92, 8%).
      After adjusting for age, estimated glomerular filtration rate, and height
      adjusted total kidney volume, ADPKD subjects with megavesicles were 10 times more
      likely to have a PKD1 than a PKD2 mutation. Among PKD1 subjects, seminal
      megavesicles occurred more frequently with nontruncating mutations with less
      severe kidney involvement. DATA CONCLUSION: ADPKD is associated with prostate
      median cysts near ejaculatory ducts. These cysts correlate with seminal
      megavesicles (dilated to >10 mm) which predict a 10-fold greater likelihood of
      PKD1 vs. PKD2 mutation. Cysts elsewhere in the prostate are not related to ADPKD.
      LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30230108
TI  - Prostate Cancer Differentiation and Aggressiveness: Assessment With a Radiomic
      Based Model vs. PI-RADS v2.
AB  - BACKGROUND: Multiparametric MRI (mp-MRI) combined with machine-aided approaches
      have shown high accuracy and sensitivity in prostate cancer (PCa) diagnosis.
      However, radiomics-based analysis has not been thoroughly compared with Prostate
      Imaging and Reporting and Data System version 2 (PI-RADS v2) scores. PURPOSE: To
      develop and validate a radiomics-based model for differentiating PCa and
      assessing its aggressiveness compared with PI-RADS v2 scores. STUDY TYPE:
      Retrospective. POPULATION: In all, 182 patients with biopsy-proven PCa and 199
      patients with a biopsy-proven absence of cancer were enrolled in our study. FIELD
      STRENGTH/SEQUENCE: Conventional and diffusion-weighted MR images (b values = 0,
      1000 sec/mm2 ) were acquired on a 3.0T MR scanner. ASSESSMENT: A total of 396
      features and 385 features were extracted from apparent diffusion coefficient
      (ADC) images and T2 WI, respectively. A predictive model was constructed for
      differentiating PCa from non-PCa and high-grade from low-grade PCa. The
      diagnostic performance of each radiomics-based model was compared with that of
      the PI-RADS v2 scores. STATISTICAL TESTS: A radiomics-based predictive model was
      constructed by logistic regression analysis. 70% of the patients were assigned to
      the training group, and the remaining were assigned to the validation group. The
      diagnostic efficacy was analyzed with receiver operating characteristic (ROC) in
      both the training and validation groups. RESULTS: For PCa versus non-PCa, the
      validation model had an area under the ROC curve (AUC) of 0.985, 0.982, and 0.999
      with T2 WI, ADC, and T2 WI&ADC features, respectively. For low-grade versus high
      grade PCa, the validation model had an AUC of 0.865, 0.888, and 0.93 with T2 WI,
      ADC, and T2 WI&ADC features, respectively. PI-RADS v2 had an AUC of 0.867 in
      differentiating PCa from non-PCa and an AUC of 0.763 in differentiating high
      grade from low-grade PCa. DATA CONCLUSION: Both the T2 WI- and ADC-based
      radiomics models showed high diagnostic efficacy and outperformed the PI-RADS v2
      scores in distinguishing cancerous vs. noncancerous prostate tissue and high
      grade vs. low-grade PCa. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J.
      Magn. Reson. Imaging 2018.

PMID- 30230109
TI  - Effect of root canal debridement on inflammatory cytokine levels.
AB  - In endodontic infections, inflammatory mediators such as cytokines are released,
      recruited and retained until the infection is eradicated. Root canal therapy is
      performed to prevent the spread of infection. The aim of this study was to
      investigate the effects of root canal debridement (cleaning and shaping) on
      periapical inflammation by measuring the levels of inflammatory cytokines,
      Interleukin-8 (IL-8) and Interleukin-10 (IL-10). The study includes twenty
      patients with pulp necrosis and asymptomatic apical periodontitis. Periradicular
      sample was collected using paper points before and after root canal debridement.
      Cytokine levels were determined by Sandwich Enzyme-Linked Immunosorbent Assay
      (ELISA). Data were analysed using paired t-test (PASW Statistics 18) (P = 0.05).
      All samples showed the presence of IL-8 and IL-10 prior to root canal
      debridement. Significantly reduced levels (P < 0.05) of IL-8 and IL-10 were
      detected after root canal debridement. In conclusion, root canal debridement
      significantly decreased the levels of the tested pro- and anti-inflammatory
      cytokine in the periradicular interstitial fluid.

PMID- 30230111
TI  - PD-L1 expression and CD8-positive T cells are associated with favorable survival
      in HER2-positive invasive breast cancer.
AB  - Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic
      suppressors of the cytotoxic immune reaction. However, to date, the combination
      of PD1/PD-L1 expression and tumor-infiltrating lymphocytes (TILs) and antigen
      presenting cells has been only minimally reported in breast carcinoma, in
      particular in relation to HER2-positive cases. The goal of this study was to
      evaluate both cellular tumoral immune reaction and PD-L1/PD1 distribution in HER2
      positive cases, as well as any associations with clinical outcome using
      conventional chemotherapy combined with HER2 blocking. Multicolor
      immunohistochemical multiplex assays simultaneously demonstrating PD1, PD-L1, and
      CD8 or PD-L1, CD3, and CD163 were performed on tissue microarrays (TMA)
      representing 216 pretreatment cases of HER2-positive invasive breast carcinoma.
      PD-L1 expression was identified in 38 cases (18%), including 12 cases (6%) with
      PD-L1 labeling of tumor cells and 26 cases (12%) with PD-L1 labeling of immune
      cells only. Ten of 12 cases with PD-L1 staining of tumor cells showed staining of
      associated immune cells as well. With this assay method, PD1 was detectable in
      many fewer cases (6 cases or 3%). PD-L1 expression was positively associated with
      high Nottingham grade, negative ER and PR, the absence of lymph node metastasis,
      and high levels of CD8+ cells. The overall survival by univariate analysis was
      positively associated with lower tumor stage, the absence of lymph node
      metastasis, PD-L1 expression, and high levels of CD8+ cells. Therefore, our data
      suggest cytotoxic immune reaction mediated by CD8-positive T cells and PD-L1
      expression may predict a better outcome in patients with HER2-positive breast
      carcinoma managed with conventional chemotherapy and HER2-blocking therapy. These
      findings recommend clinical trials utilizing checkpoint blocking immunotherapy in
      some form for HER2-positive breast cancer.

PMID- 30230112
TI  - Characterizing Structural Changes With Devolving Remyelination Following
      Experimental Demyelination Using High Angular Resolution Diffusion MRI and
      Texture Analysis.
AB  - BACKGROUND: Changes in myelin integrity are associated with the pathophysiology
      of many neurological diseases, including multiple sclerosis. However, noninvasive
      measurement of myelin injury and repair remains challenging. Advanced MRI
      techniques including diffusion tensor imaging (DTI), neurite orientation
      dispersion and density index (NODDI), and texture analysis have shown promise in
      quantifying subtle abnormalities in white matter structure. PURPOSE: To determine
      whether and how these advanced imaging methods help understand remyelination
      changes after demyelination using a mouse model. STUDY TYPE: Prospective,
      longitudinal. ANIMAL MODEL: Demyelination was induced in the thoracic spinal cord
      of 21 mice using the chemical toxin lysolecithin. FIELD STRENGTH/SEQUENCES: 9.4T
      ASSESSMENT: Imaging was done at day 7 (demyelination) and days 14 to 35 (ongoing
      remyelination) postsurgery, followed by histology. Image analysis focused on both
      lesions and peri-lesional areas where remyelination began. In histology, we
      quantified the complexity of tissue alignment using angular entropy, in addition
      to staining area. STATISTICAL ANALYSIS: Two-way analysis of variance was
      performed for assessing differences between tissue types and across timepoints,
      followed by post-hoc analysis to correct for multiple comparisons (P < 0.05).
      RESULTS: All diffusion and texture parameters were worse in lesions than the
      control tissue (P < 0.05) except orientation dispersion index (ODI) and neurite
      density index (NDI) over late remyelination. Longitudinally, ODI decreased and
      NDI increased persistently in both lesions and peri-lesion regions (P < 0.05).
      Fractional anisotropy showed a mild decrease at day 35 after increase, when
      lesion texture heterogeneity showed a trend to decrease (P > 0.05). Both lesion
      size and angular entropy decreased over time, and no change in any measure in the
      control tissue. DATA CONCLUSION: Diffusion and MRI texture metrics may provide
      compensatory information on myelin repair and ODI and NDI could be sensitive
      measures of evolving remyelination, deserving further validation. LEVEL OF
      EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

PMID- 30230113
TI  - Comparison of Magee and Oncotype DX Recurrence Scores in estrogen receptor
      positive breast cancers.
AB  - Data from pathology reports of estrogen receptor positive (ER+) breast cancers
      with Ki67 < 14% (luminal-A; n = 128) and Ki67 >= 14% (luminal-B; n = 100) were
      entered into the automatic recurrence score (RS) calculator accessible at the
      University of Pittsburgh Department of Pathology website. Using RS obtained with
      Magee equations #1 and #3, an average modified Magee recurrence score (AMM RS)
      was calculated for each tumor. The AMM RS and the Oncotype DX RS (Onco RS) were
      compared per tumor and associated with follow-up. AMM RS and Onco RS agreed in
      64.9% (148 of 228) breast cancers (70.3% luminal-A and 58% luminal-B). There was
      only one two-step (low risk by Onco/high risk by AMM) RS disagreement. This
      luminal-B patient is alive without recurrence and free of tumor at 46 months
      postdiagnosis. Low-risk/intermediate-risk disagreements comprised 94.7% (36 of
      38) and 69% (29 of 42) of the RS disagreements in the luminal-A and luminal-B
      groups, respectively (P = 0.004). In luminal-A, there were only two
      intermediate/high-risk disagreements; both high-risk ratings were by Onco RS. In
      luminal-B, there were 12 intermediate/high-risk disagreements; 11 of the high
      risk ratings were by Onco RS. 100% (3 of 3) luminal-A tumors and 75% (6 of 8)
      luminal-B tumors that were high risk by AMM RS were also high risk by Onco RS.
      Eight tumors recurred and/or metastasized. AMM RS and Onco RS disagreed in only
      two of these eight tumors. The high percentage of tumors scored as intermediate
      risk (50% by AMM RS and 39% by Onco RS) is a major limitation of both scoring
      algorithms.

PMID- 30230114
TI  - Radiomics Analysis of Multiparametric MRI Evaluates the Pathological Features of
      Cervical Squamous Cell Carcinoma.
AB  - BACKGROUND: Robust parameters to evaluate pathological aggressiveness are needed
      to provide individualized therapy for cervical cancer patients. PURPOSE: To
      investigate the radiomics analysis of multiparametric MRI to evaluate tumor
      grade, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis of
      cervical squamous cell carcinoma (CSCC). STUDY TYPE: Retrospective. SUBJECTS:
      Fifty-six patients with histopathologically confirmed CSCC. FIELD
      STRENGTH/SEQUENCE: 3T, axial T2 and T2 with fat suppression (FS), diffusion
      weighted imaging (DWI) (multi-b values), axial dynamic contrast enhanced (DCE)
      MRI (8 sec temporal resolution). ASSESSMENT: Regions of interest were drawn
      around the tumor on each axial slice and fused to generate the whole tumor
      volume. Sixty-six radiomics features were derived from each image sequence,
      including axial T2 and T2 FS, ADC maps, and Ktrans , Ve , and Vp maps from DCE
      MRI. STATISTICAL TESTS: A univariate analysis was performed to assess each
      parameter's association with tumor grade and the presence of lymphovascular space
      invasion (LVSI) and lymph node (LN) metastasis. A principal component analysis
      was employed for dimension reduction and to generate new discriminative
      valuables. Using logistic regression, a discriminative model of each parameter
      was built and a receiver operating characteristic curve (ROC) was generated.
      RESULTS: The area under the ROC curve (AUC) of anatomical, diffusion, and
      permeability parameters in discriminating the presence of LVSI ranged from 0.659
      to 0.814, with Ve showing the best discriminative value. The AUC in
      discriminating the presence of LN metastasis and distinguishing tumor grade
      ranged from 0.747 to 0.850, 0.668 to 0.757, with ADC and Ve showing the best
      discriminative value, respectively. DATA CONCLUSION: Functional maps exhibit
      better discriminative values than anatomical images for discriminating the
      pathological features of CSCC, with ADC maps showing the best discrimination
      performance for LN metastasis and Ve maps showing the best discriminative value
      for LVSI and tumor grade. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J.
      Magn. Reson. Imaging 2018.

PMID- 30230115
TI  - Evaluation of root canal morphology of maxillary premolars: a cone-beam computed
      tomography study.
AB  - The aim of this study was to evaluate the root canal configuration of maxillary
      premolars using cone-beam computed tomography (CBCT). CBCT images of 999
      maxillary premolars from a database were analysed to determine the frequency of
      the number of roots, root canals and Vertucci's classification. The associations
      among these variables were evaluated by Chi-square test (P < 0.05). In the first
      premolars, 42.2% of single-rooted teeth had a type II configuration, whereas
      98.7% of 2-rooted teeth showed type IV. In the second premolars, type I was the
      most prevalent (49.9%). The presence of two roots was more prevalent in first
      premolars, and the presence of one root was more prevalent in second premolars (P
      < 0.05). Male patients had a higher percentage of two roots compared with female
      patients (P < 0.05). Type IV and I was more prevalent in first and second
      premolars respectively (P < 0.05). There was a high frequency of 2-rooted and
      single-rooted teeth among maxillary first and second premolars respectively.

PMID- 30230116
TI  - Intraoperative hypotension and flap loss in free tissue transfer surgery of the
      head and neck.
AB  - BACKGROUND: In free flap head and neck reconstructions, hemodynamic management is
      complicated by the deleterious effects of excessive crystalloid administration.
      Patients may undergo periods of hypotension or excess fluid administration. The
      purpose of this study was to present our examination of the hypotheses that
      intraoperative hypotension and blood pressure lability are associated with
      increased fluid administration and flap failure. METHODS: We reviewed the records
      of 445 patients undergoing head and neck surgery involving free tissue transfer.
      We used multivariate logistic regression to examine the relationship between
      hemodynamic variables and flap loss (primary outcome) and other complications.
      RESULTS: On multivariate analysis, intraoperative hypotension and large-volume
      fluid administration were associated with flap loss. Neither blood pressure
      lability nor vasopressor administration was significantly associated to our
      primary outcome. CONCLUSIONS: Intraoperative hypotension is associated to flap
      failure in head and neck free tissue transfer surgeries, as is large-volume fluid
      administration.

PMID- 30230117
TI  - Breast cancer histopathology is predictive of low-risk Oncotype Dx recurrence
      score.
AB  - BACKGROUND: Oncotype Dx is a genetic test that has been incorporated into the
      2017 AJCC breast cancer staging system for ER positive, HER2-negative, lymph node
      negative patients to predict the risk of recurrence. Recent data suggest that
      immunohistochemistry (ER, PR, HER2, and Ki-67) and histologic subtype may
      identify patients that will not benefit from Oncotype Dx testing. METHODS: A
      total of 371 patients underwent Oncotype Dx testing at our institution from 2012
      to 2016. Oncotype recurrence score was categorized as low- (ORS = 0-10),
      intermediate- (11-25), or high risk (26-100). Invasive carcinomas were
      categorized based on histologic subtype as "favorable" (mucinous, tubular,
      cribriform, tubulolobular, and lobular) and "unfavorable" (ductal, mixed ductal
      and lobular, and micropapillary carcinoma). All cases were estrogen receptor
      positive and HER2-negative. Clinical and histologic predictors of low-risk ORS
      were assessed in univariate and multivariate logistic regression. RESULTS: A
      total of 371 patients were categorized by ORS as low risk (n = 85, 22.9%),
      intermediate risk (n = 244, 65.8%), and high risk (n = 42, 11.3%). The histologic
      subtypes with the highest percentage of high-risk ORS were invasive
      micropapillary (n = 4/17, 23.5%), pleomorphic lobular (n = 2/10, 20%), and ductal
      carcinoma (n = 28/235, 11.9%). Low-grade invasive carcinomas with favorable
      histology rarely had a high-risk ORS (n = 1/97, 1%). In a simple multivariable
      model, favorable histologic subtype (OR = 2.39, 95% CI: 1.10 to 5.15, P = 0.026),
      and histologic grade (OR = 1.76, 95% CI: 1.07 to 2.90, P = 0.025) were the only
      significant predictors of an ORS less than 11 in estrogen receptor positive, HER2
      negative, and lymph node-negative patients. CONCLUSION: We question the utility
      of performing Oncotype Dx in subtypes of invasive carcinoma that are associated
      with excellent prognosis. We propose that immunohistochemistry for ER, PR, and
      HER2 is sufficient for patients with low-grade invasive carcinomas and can be
      used as a surrogate for Oncotype Dx.

PMID- 30230118
TI  - 18F-FPEB PET/CT Shows mGluR5 Upregulation in Parkinson's Disease.
AB  - BACKGROUND AND PURPOSE: Dopamine and glutamate reciprocally regulate each other
      in some of the neurocircuits affected by Parkinson's disease (PD). The objective
      of this pilot study was to explore relationships between these neurotransmitter
      systems with positron emission tomography. METHODS: The sample consisted of nine
      patients with PD and eight healthy volunteers (HVs). Dynamic images of the brain
      were acquired after the IV administration of ~370 MBq (10 mCi) of [11 C]PE2i, a
      dopamine transporter (DaT) imaging agent, and ~185 MBq (~5 mCi) of [18 F]FPEB, a
      selective metabotropic glutamate receptor 5 (mGluR5) antagonist. Multiple volumes
      of interest were semiautomatically placed on contemporaneously acquired MRI
      scans. Nondisplaceable binding potentials (BPND ) were calculated with the Logan
      reference tissue model using cerebellar white matter as the reference region.
      RESULTS: The findings showed that average [18 F]FPEB BPND values were slightly
      more than 20% higher in PD than HVs in several mesocortical regions, including
      the bilateral putamen (P = .01), hippocampus (P = .02), and amygdala (P = .05).
      Average [11 C]PE2i BPND was significantly reduced by about half or more in
      patients with PD in the bilateral caudate (P < .001) and putamen (P < .001).
      CONCLUSIONS: mGluR5 seems upregulated in strategic dopaminergic brain regions
      adversely affected by PD. The findings seem to confirm that DaT tracers are
      better discriminatory biomarkers for diagnosing PD; however, mGluR5 tracers might
      deserve further exploration as potential biomarkers of response in clinical
      trials.

PMID- 30230119
TI  - Direct-to-implant breast reconstruction: Higher complication rate vs cosmetic
      benefits.
AB  - BACKGROUND: Since skin- and nipple-sparing mastectomies (SSM/NSM) are now
      considered oncologically safe options, the number of immediate implant-based
      breast reconstructions (IBBR) has increased. We present our experience with
      different techniques of immediate and delayed IBBR over a period of 5 years.
      METHODS: A single center, retrospective, cohort study was performed from January
      2008 to January 2013. Complications, reconstructive failure, contralateral
      adjustment, cosmetic outcome, patient's quality of life, and the thickness of the
      overlying tissue were compared between different techniques of immediate and
      delayed IBBR. RESULTS: A total of 180 patients who underwent immediate (n = 148,
      82.2%) or delayed (n = 32, 17.8%) IBBR after SSM (n = 62, 34.4%), NSM (n = 21,
      11.7%), or total mastectomy (n = 97, 53.9%) were included. The mean follow-up was
      46 months. Immediate IBBR was associated with better cosmetic outcomes (P =
      0.026), fewer surgical interventions (P = 0.017), and better quality of life (P =
      0.004). Patients with NSM showed the best quality of life results (P =< 0.001)
      and the best cosmetic outcome (P = 0.001). While immediate IBBR with direct-to
      implant procedures achieved a trend toward best cosmetic outcomes (P = 0.66), it
      was associated with the highest complication rate (37.1%) compared to permanent
      expanders (10.5%) and a two-stage expander-to-implant procedure (22.9%; P =
      0.013) without a significant difference in the rate of implant loss (P = 0.51).
      CONCLUSION: Whenever oncologically feasible, immediate IBBR should be offered to
      the patient. The advantages of immediate IBBR with a direct-to-implant procedure
      such as better cosmetic outcome and fewer surgical interventions should be
      weighed up against the relatively high overall complication rate associated with
      this procedure.

PMID- 30230120
TI  - Epicardial ventricular tachycardia in ischemic cardiomyopathy: Prevalence,
      electrophysiological characteristics, and long-term ablation outcomes.
AB  - INTRODUCTION: The characteristics of the epicardial (EPI) substrate responsible
      for ventricular tachycardia (VT) in ischemic cardiomyopathy (ICM) are undefined,
      and data on the long-term outcomes of EPI catheter ablation limited. We evaluated
      the prevalence, electrophysiologic features, and outcomes of catheter ablation of
      EPI VT in ICM. METHODS AND RESULTS: From December 2010 to June 2013, a total of
      13 of 93 (14%) patients with ICM underwent catheter ablation at our institution
      and had conclusive evidence of critical EPI substrate demonstrated to participate
      in VT with activation, entrainment and/or pace mapping during sinus rhythm (two
      other patients underwent EPI mapping but had no optimal ablation targets). The
      electrophysiologic substrate characteristics and activation/entrainment mapping
      data were compared with a reference group of ICM patients without evidence of
      critical EPI substrate (N = 44), defined as a complete procedural success
      (noninducibility of any VT at programmed stimulation) after endocardial (ENDO)
      only ablation. Patients with failed EPI access (N = 2) or history of cardiac
      surgery (N = 92) were excluded from the study. All 13 patients had evidence of
      abnormal EPI substrate with fractionated/late/split electrograms and low-bipolar
      voltage areas. The critical VT ablation sites were all located within the EPI
      bipolar "dense" scar (<1.0 mV) opposite the ENDO bipolar scar in 77% of cases and
      extending beyond the ENDO bipolar scar (within the ENDO unipolar low-voltage
      area) in the remaining patients. Compared with the reference ENDO-only group,
      patients with EPI VT had a smaller ENDO bipolar scar area, 54.0 (37.1-84) vs 86.7
      (55.6-112) cm2 ; P = 0.0159, with a similar extent of ENDO unipolar low voltage.
      No other substrate characteristics or location differed between the two groups.
      After 35.2 +/- 24.2 months of follow-up, VT-free survival was 73% in patients
      with EPI VT compared with 66% in the ENDO-only group (log-rank P = 0.56).
      CONCLUSIONS: The presence of the critical EPI substrate responsible for VT can be
      demonstrated in at least 14% of patients with ICM. The majority of EPI critical
      ablation sites are distributed opposite the ENDO bipolar scar area and catheter
      ablation is effective in achieving long-term arrhythmia control.

PMID- 30230121
TI  - Abnormal repolarization: A common electrocardiographic finding in patients with
      epilepsy.
AB  - BACKGROUND: Recently, certain forms of early repolarization (ER) on
      electrocardiograms (ECGs) have been considered a possible marker of increased
      sudden cardiac death risk. The frequency, characteristics, and clinical follow-up
      with which these forms of ER are present in epilepsy patients, and whether or not
      abnormal ER contributes to sudden unexplained death in epilepsy patients (SUDEP)
      is unknown. METHODS AND RESULTS: The amplitude of J peak and ST-segment
      morphology after ER on 12-lead ECGs were assessed in 354 epilepsy patients (age,
      33 +/- 16 years; 54% men) and 140 age- and sex-matched control subjects (age, 31
      +/- 12 years; 50% men). Abnormal ER prevalence (J-wave amplitude >=0.1 mV) was
      greater in epilepsy patients (19.8%) compared with controls (8.6%; P = 0.002) in
      inferior ECG leads but not in lateral leads ( P = 0.40). ER with a horizontal or
      descending ST segment was also more prevalent in epilepsy patients ( P < 0.001).
      After introducing antiepileptic drugs in 36 epilepsy patients, there were no
      significant ER changes. Similarly, in 64 epilepsy patients with seizure
      suppression, ER comparison before and after seizure control revealed no
      significant changes. Male gender was the only significant predictor of abnormal
      ER in epilepsy patients ( P = 0.03). During a median follow-up of 7 years, SUDEP
      occurred in two patients, one with abnormal ER. CONCLUSIONS: Abnormal ER may be
      more prevalent in epilepsy patients than in controls and is not altered by
      antiepileptic drugs or achievement of epilepsy suppression. The relation of
      abnormal ER to SUDEP remains in need of further study.

PMID- 30230122
TI  - Relationship between call rate per individual and genotyping accuracy of bovine
      single-nucleotide polymorphism array using deoxyribonucleic acid of various
      qualities.
AB  - Single nucleotide polymorphism (SNP) arrays are widely used for genetic and
      genomic analyses in cattle breeding. However, the relationship among sample
      genotyping efficiency (call rate per individual), accuracy of SNP genotypes, and
      DNA quality (integrity, concentration, and mixture of DNA, i.e., chimerism)
      remains unknown. We determined the effect of DNA quality on call rate per
      individual and accuracy of SNP genotypes using artificial DNA samples of various
      qualities. Integrity and concentration of DNA were less sensitive to call rate
      per individual and accuracy of genotyping in the SNP array. Chimerism strongly
      affected call rate per individual and accuracy of SNP genotypes. Artificial
      chimerism experiments showed that relative to unmixed DNA, the genotypic matching
      error (%) of mixed DNAs linearly increased with mix ratio, whereas the call rate
      per individual in some samples at 50% mix ratio was >0.95. However, individuals
      with higher chimerism were readily identified based on standard deviation of B
      allele frequency (BAF) and BAF distribution across the genome from SNP array
      data. Thus, we effectively managed the balance by maximizing genotyping accuracy
      and minimizing the number of samples for re-genotyping by using quality control
      for combining call rate per individual with BAF.

PMID- 30230123
TI  - The dopamine transporter VNTR polymorphism moderates the relationship between
      acute response to alcohol and future alcohol use disorder symptoms.
AB  - Alcohol use disorder (AUD) is a genetically influenced disease with peak onset in
      young adulthood. Identification of factors that predict whether AUD symptoms will
      diminish or persist after young adulthood is a critical public health need. King
      and colleagues previously reported that acute response to alcohol predicted
      future AUD symptom trajectory. Genes associated with brain dopamine signaling,
      which underlies alcohol's rewarding effects, might influence this finding. This
      study analyzed whether variation at a variable number tandem repeat polymorphism
      in DAT1/SLC6A3, the gene encoding the dopamine transporter, moderated the
      predictive relationships between acute response to alcohol and future AUD
      symptoms among participants enrolled in the Chicago Social Drinking Project
      (first two cohorts). Heavy-drinking young adults (N = 197) completed an alcohol
      challenge, in which acute response (liking, wanting, stimulation, and sedation)
      was measured. Alcohol use disorder symptoms were assessed over the following 6
      years. DAT1 genotype significantly moderated the interactions between follow-up
      time and alcohol liking (P = 0.006) and wanting (P = 0.006) in predicting future
      AUD symptoms. These predictive effects were strongest among participants who
      carried the DAT1 9-repeat allele, previously associated with enhanced striatal
      dopamine tone relative to the 10-repeat allele. Exploratory analyses indicated
      that DAT1 effects on the relationship between alcohol liking and AUD symptoms
      appeared stronger for females (n = 79) than males (n = 118) (P = 0.0496). These
      data suggest that heavy-drinking DAT1 9-repeat allele carriers who display high
      alcohol-induced reward in young adulthood may be predisposed to persistent AUD
      symptoms and support combining genotypic and phenotypic information to predict
      future AUD risk.

PMID- 30230124
TI  - Intestinal involvement in amyloidosis is a sequential process.
AB  - BACKGROUND: Gastrointestinal amyloidosis causes dysmotility. A comprehensive
      histological analysis to explain these symptoms is lacking. Therefore, we
      systematically examined histological features of intestinal dysmotility in
      patients with AL and AA amyloidosis, compared to controls. METHODS: Autopsy
      tissue material from small bowel and colon was used for histological
      (semiquantitative) evaluation of the mucosa, blood vessels, muscular layers,
      enteric nervous system (ENS) and the interstitial cells of Cajal (ICC), using
      hematoxylin and eosin, periodic acid Schiff, Elastic von Gieson and Congo red
      staining, and immunohistochemistry with alpha-smooth muscle actin, HuC/D, S100
      and CD117 antibodies, according to guidelines of the Gastro 2009 International
      Working Group. KEY RESULTS: Amyloid deposits were present in the vascular walls
      of all amyloidosis patients. In the mucosa, amyloid was found in 67% of AA
      patients. The muscular layers were involved in 64% of amyloidosis patients, most
      prominent in AA patients, associated with the presence of polyglucosan inclusion
      bodies, but not with either abnormal alpha-actin patterns or fibrosis. Amyloid in
      the muscularis propria surrounding the myenteric plexus was found, but not inside
      the myenteric plexus. These deposits might be related to loss of the ICC network,
      but there was no association with decreased neuronal or nerve fiber density.
      CONCLUSIONS & INFERENCES: We hypothesize that intestinal dysmotility in
      amyloidosis patients is a sequential process: amyloid deposition starts in the
      vasculature, followed by involvement of the muscular layers, ICC loss, and
      potentially affect the myenteric plexus. This final stage may be accompanied by
      clinical symptoms of severe intestinal dysmotility.

PMID- 30230125
TI  - The effects of import competition on health in the local economy.
AB  - We provide evidence that average mental, physical, and general health worsens for
      employed workers in local U.S. labor markets exposed to greater import
      competition from China. The effects are greatest for mental health. Moving a
      region from the 25th to 75th percentiles of import exposure corresponds to a 7.8%
      increase in the morbidity of poor mental health, adding about 3 days of poor
      mental health per year for the average adult. Concurrently, the ability to afford
      health care decreases. Our results complement documented consequences of import
      competition on labor markets and temporary business cycle shocks on health
      outcomes.

PMID- 30230126
TI  - Detection and genomic analysis of genital group B streptococcus in pregnant
      Korean women.
AB  - AIM: Group B streptococcus (GBS) is a leading cause of life-threatening bacterial
      infections among newborns, and neonates born to heavily colonized women may be
      subject to vertical transmission. We sought to determine an appropriate detection
      method for genital GBS in pregnant women by comparing culture-based methods and
      real-time polymerase chain reaction (PCR). In addition, we performed molecular
      serotyping and multilocus sequence typing (MLST) on isolates. METHODS: A total of
      150 pregnant women were enrolled and underwent vaginal-rectal swabbing at 16-40
      weeks of gestation. GBS was identified by conventional culture and real-time PCR
      with or without enrichment. Molecular serotyping and MLST were performed on
      isolates. RESULTS: Overall genital GBS positive rate among the 150 study subjects
      was 17.3%. Direct culture identified 18 (12.0%) positive specimens, enrichment
      culture 22 (14.6%), direct PCR 24 (16.0%) and enrichment PCR 25 (16.6%). The
      sensitivity and specificity by direct and enrichment PCR were as follows: for
      direct PCR, 90.9% and 96.9%, respectively; and for enrichment PCR, 95.5% and
      96.9%, respectively. Resistance rates to clindamycin and erythromycin were 33.3%
      and 19.1%, respectively. Serotype III-1 was the most common (26.3%), followed by
      serotype Ib (21.1%), III-3 (15.8%), V (15.8%), II (10.5%), IV (5.3%) and VI
      (5.3%). Most common sequence types (ST) were ST-1, ST-19 and ST-862 (15.8%),
      followed by ST-2 and ST-654 (10.5%). CONCLUSION: Direct real-time PCR using
      vaginal-rectal specimen could be used for detecting GBS in emergent conditions.
      Molecular serotypes III, Ib and V were most common. MLST analysis frequently
      presented ST-1, ST-19 and ST-862.

PMID- 30230127
TI  - The use of chromophore gel-assisted blue light phototherapy (Lumiheal) for the
      treatment of surgical site infections in breast surgery.

PMID- 30230128
TI  - Enabling Fluorinated MOF-Based Membranes for Simultaneous Removal of H2 S and CO2
      from Natural Gas.
AB  - Membrane-based gas separations are energy efficient processes; however, major
      challenges remain to develop high-performance membranes enabling the replacement
      of conventional separation processes. Herein, a new fluorinated MOF-based mixed
      matrix membrane is reported, which is formed by incorporating the MOF crystals
      into selected polymers via a facile mixed-matrix approach. By finely controlling
      the molecular transport in the channels through the MOF apertures tuned by metal
      pillars and at the MOF-polymer interfaces, the resulting fluorinated MOF-based
      membranes exhibit excellent molecular sieving properties. These materials
      significantly outperform state-of-the-art membranes for simultaneous removal of
      H2 S and CO2 from natural gas-a challenging and economically important
      application. The robust fluorinated MOFs (NbOFFIVE-1-Ni, AlFFIVE-1-Ni), pave a
      way to efficient membrane separation processes that require precise
      discrimination of closely sized molecules.

PMID- 30230129
TI  - Efficacy of different irrigation methods on dentinal tubule penetration of
      Chlorhexidine, QMix and Irritrol: A confocal laser scanning microscopy study.
AB  - The aim of this in vitro study was to compare the percentage of penetration of
      three final irrigant into the dentinal tubules after application of several
      irrigation techniques. Mandibular premolars were divided into nine groups (n:10):
      chlorhexidine (CHX) + conventional syringe irrigation (CI), CHX + EndoActivator
      (SI), CHX + Er,Cr:YSGG laser (LAI), QMix + CI, QMix + SI, QMix + LAI, Irritrol +
      CI, Irritrol + SI and Irritrol + LAI. Following irrigation, all roots were
      horizontally sectioned at 2 mm and 5 mm from the apex and examined using a
      confocal laser scanning microscopy. QMix exhibited a significantly higher
      penetration percentage than CHX at the apical section (P < 0.05). In the Irritrol
      group, SI displayed a significantly higher penetration area than CI in the middle
      section. Statistically significant differences were also determined between
      middle and apical section (P < 0.05). Use of QMix with different agitation
      technique seems advantageous in dentinal tubule penetration.

PMID- 30230130
TI  - Asia & Oceania Federation of Obstetrics and Gynaecology, Maternal Fetal Medicine
      Committee's consensus statements on screening for hyperglycemia in pregnancy.
AB  - These are consensus statements on screening for hyperglycemia in pregnancy
      derived from AOFOG MFM Committee's Hyperglycemia in Pregnancy Consensus Working
      Group during a workshop in Singapore on 13 January 2018.

PMID- 30230131
TI  - Malignant peripheral nerve sheath tumor of the breast in a patient with
      neurofibromatosis 1.

PMID- 30230132
TI  - First trimester screening for preterm and term pre-eclampsia by maternal
      characteristics and biophysical markers in a low-risk population.
AB  - AIM: To develop a combined predictive model for preterm and term pre-eclampsia
      (PE) during the first trimester of pregnancy. METHODS: This investigation was a
      nested case-control study in singleton pregnancies at the Maternal-Fetal Medicine
      Unit, University of Chile Hospital. A priori risks for preterm and term PE were
      calculated by multivariate logistic regression analyses. Biophysical markers were
      log10 -transformed and expressed as multiples of the median. A multivariate
      logistic regression analysis was used to estimate a combined predictive model of
      preterm and term PE. Detection rates at different cut-off points were determined
      by a receiver operator curve analysis of a posteriori risks. RESULTS: First
      trimester mean arterial pressure and uterine artery Doppler pulsatility index
      were significantly higher in women who develop PE than in the unaffected group.
      The detection rate of preterm PE based on maternal characteristics and
      biophysical markers was 72% at a 10% false-positive rate, corresponding to a cut
      off risk of 1 in 50. The detection rate for term PE was 30% at a 10% false
      positive rate. CONCLUSION: Preterm PE can be predicted by a combination of
      maternal characteristics and biophysical markers. However, first trimester
      screening is less valuable for term PE.

PMID- 30230133
TI  - Hydrogen sulfide downregulates colonic afferent sensitivity by a nitric oxide
      synthase-dependent mechanism in mice.
AB  - BACKGROUND: The effect of hydrogen sulfide (H2 S) on visceral nociception is
      elusive. The conflicting evidence of its pro- and antinociceptive effects raises
      a series of questions with respect to the effect of H2 S on colonic afferent
      activity and the underlying mechanism, which was further elucidated in this
      study. METHODS: Colonic mesenteric afferent nerve spikes of normal male C57BL/6J
      mice, Cbs+/- mice, and Wistar rats were recorded in vitro. The abdominal
      withdrawal reflex (AWR) induced by colorectal distension (CRD) was evaluated in
      Cbs+/- mice and WT littermates. KEY RESULTS: Sodium hydrosulfide (NaHS)
      significantly decreased colonic afferent spontaneous discharge, chemosensitivity
      to bradykinin, mechanosensitivity to ramp distention, and intraluminal pressure
      in mice. Reducing the relaxant action of NaHS on intestinal smooth muscle using
      the nonspecific K+ channel blocker TEA (10 mmol/L) did not block the inhibition
      of NaHS on afferent nerve activity. The inhibitory effects of NaHS (0.5 mmol/L)
      on colonic afferent sensitivity were largely eliminated by the pretreatment with
      nonspecific NOS inhibitor NG -Methyl-l-arginine acetate salt (1 mmol/L), the
      specific nNOS inhibitor NPLA (1 MUmol/L), or N-type Ca2+ channel blocker omega
      conotoxin GVIA (1 MUmol/L). Compared with WT mice, Cbs+/- mice showed increased
      mesenteric afferent sensitivity to colonic distention and enhanced hyperalgesic
      response to CRD. Intraperitoneal administration of NaHS (60 MUmol/kg) alleviated
      the nociception response to CRD in both Cbs+/- and WT mice. CONCLUSIONS AND
      INFERENCES: H2 S downregulates colonic mesenteric afferent sensitivity by a nNOS
      dependent mechanism in mice. Our findings may demonstrate a new mechanism for the
      antinociceptive effect of H2 S in colon.

PMID- 30230134
TI  - Altered intestinal antibacterial gene expression response profile in irritable
      bowel syndrome is linked to bacterial composition and immune activation.
AB  - BACKGROUND: Immune activity and gut microbiota may impact the pathophysiology of
      irritable bowel syndrome (IBS). We aimed to determine whether antibacterial gene
      expression of immune activity-defined IBS patients differed compared to healthy
      subjects (HS) and ulcerative colitis (UC) patients and whether antibacterial
      profiles reflected gut microbiota composition and IBS symptoms. METHODS:
      Expression of 84 antibacterial genes in biopsies from HS, IBS patients (clustered
      according to immune activity (systemic and intestinal cytokines): immunonormal or
      immunoactive), and UC patients was assessed by Human Antibacterial Response RT2
      Profiler PCR Array. In IBS patients, 16S rRNA gene sequencing of fecal and
      mucosal bacteria was performed and symptom pattern and severity were assessed.
      KEY RESULTS: Intestinal antibacterial gene expression profiles differed between
      IBS patients (n = 31) and HS (n = 16), but did not differ between IBS subgroups
      based on bowel habit predominance or symptom severity. Based on previously
      identified IBS clusters, IBS patients with normal (n = 15) and enhanced immune
      activity (n = 16) had clearly separate antibacterial gene expression profiles
      from active UC patients (n = 12) and differed compared to each other and to HS.
      The differences in antibacterial gene expression profiles between immunonormal
      and immunoactive IBS patients were also reflected in distinct fecal and mucosal
      microbiota composition profiles, but not in symptom pattern or severity.
      CONCLUSIONS & INFERENCES: This study demonstrates an altered antibacterial gene
      expression profile in IBS patients compared to HS and UC patients. While not
      linked to symptoms, immune activity-defined IBS clusters showed different
      intestinal antibacterial gene expression and distinct fecal and mucosal bacterial
      profiles.

PMID- 30230135
TI  - Successful treatment of erythrodermic pityriasis rubra pilaris with acitretin.

PMID- 30230136
TI  - COMbined Physical and somatoSEnsory training after stroke: Development and
      description of a novel intervention to improve upper limb function.
AB  - BACKGROUND AND PURPOSE: After stroke, reach-to-grasp goal-directed movements are
      disrupted as a result of both residual motor and somatosensory impairments. This
      report describes the rationale and development of a new upper limb stroke
      rehabilitation intervention known as COMPoSE: "COMbined Physical and
      somatoSEnsory training," designed to improve somatosensory and motor deficits in
      the upper limb after stroke. A standardized training matrix has been developed to
      facilitate intervention delivery. METHODS: The COMPoSE intervention was developed
      through the following stages: (a) Definition and operationalization of
      somatosensory and motor variables used in training sensation and movement after
      stroke; (b) development of methods to give feedback to enhance skill acquisition;
      and (c) Combination of somatosensory and motor variables, and feedback, into a
      standardized training matrix. The reporting of the COMPoSE intervention adheres
      to the recommendations of the Template for Intervention Description and
      Replication checklist to facilitate replication of the intervention in the
      future. RESULTS: The essential features of COMPoSE include combined somatosensory
      motor training variables (grasp pressure, distance, object size, crushability,
      surface texture, and friction), feedback, and calibration using a haptic device
      providing measures of grasp pressure, use of anticipation trials, and high-dose
      repetitive task practice. Ten treatment sessions are delivered over 3 weeks,
      using a standardized matrix for treatment delivery. CONCLUSION: COMPoSE is a new
      intervention that combines somatosensory and movement training, delivered
      synchronously, within the same intervention, and within the same task.

PMID- 30230138
TI  - Do children's number words begin noisy?
AB  - How do children acquire exact meanings for number words like three or forty
      seven? In recent years, a lively debate has probed the cognitive systems that
      support learning, with some arguing that an evolutionarily ancient "approximate
      number system" drives early number word meanings, and others arguing that
      learning is supported chiefly by representations of small sets of discrete
      individuals. This debate has centered around the findings generated by Wynn's (,
      ) Give-a-Number task, which she used to categorize children into discrete "knower
      level" stages. Early reports confirmed Wynn's analysis, and took these stages to
      support the "small sets" hypothesis. However, more recent studies have disputed
      this analysis, and have argued that Give-a-Number data reveal a strong role for
      approximate number representations. In the present study, we use previously
      collected Give-a-Number data to replicate the analyses of these past studies, and
      to show that differences between past studies are due to assumptions made in
      analyses, rather than to differences in data themselves. We also show how Give-a
      Number data violate the assumptions of parametric tests used in past studies.
      Based on simple non-parametric tests and model simulations, we conclude that (a)
      before children learn exact meanings for words like one, two, three, and four,
      they first acquire noisy preliminary meanings for these words, (b) there is no
      reliable evidence of preliminary meanings for larger meanings, and (c) Give-a
      Number cannot be used to readily identify signatures of the approximate number
      system.

PMID- 30230139
TI  - 24/7 usage of continence pads and quality of life impairment in women with
      urinary incontinence.
AB  - AIMS: To compare quality of life (QoL) in women with urinary incontinence (UI)
      using continence pads during the day versus all day and night; to identify risk
      factors for a 24-hour pad use; to calculate quality-adjusted life years (QALY).
      METHODS: A cross-sectional study in 331 women with lower urinary tract symptoms
      referred to urogynaecologic examination was conducted. Main outcome measures were
      the scores of King's Health Questionnaire (KHQ), clinical data, and KHQ-derived
      utility values. RESULTS: A total of 270 women with UI were recruited: 176 (57.3%)
      using continence pads only during the day (group I) and 94 (30.6%) for 24 hours
      (group II). The groups did not differ in terms of age, menopause, parity, type of
      UI, stage of POP-Q, and percentage of sexually active subjects. Group II had
      significantly higher body mass index (BMI) and lower education than group I (P <
      0.05). QoL was significantly deteriorated in group II in KHQ Global score and in
      all domains except one (General Health). Risk factors for 24 hours pad use were
      as follows: BMI >= 30 vs BMI 25-30 (OR = 2.02 (1.09-3.73), P = 0.037), higher
      scores in KHQ Severity measures (OR = 1.03 (1.02-1.04), P < 0.001), KHQ Global
      score (OR = 1.03 (1.02-1.05), P < 0.001) and primary compared to secondary (OR =
      0.4 (0.19-0.84)) or higher education (OR = 0.41 (0.18-0.94), P < 0.05). Annual
      QALY was significantly lower in group II (0.9288 +/- 0.03 vs 0.9432 +/- 0.03, P <
      0.001). CONCLUSION: One-third of women with UI used continence pads for 24 hours.
      Among these patients QoL and QALY were found lower compared to women using
      continence pads only during the day. KHQ Severity measures domain was an
      independent predictor for a 24-hour usage of continence pads.

PMID- 30230137
TI  - Treatable traits can be identified in a severe asthma registry and predict future
      exacerbations.
AB  - BACKGROUND AND OBJECTIVE: A new taxonomic and management approach, termed
      treatable traits, has been proposed for airway diseases including severe asthma.
      This study examined whether treatable traits could be identified using registry
      data and whether particular treatable traits were associated with future
      exacerbation risk. METHODS: The Australasian Severe Asthma Web-Based Database
      (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102
      participants with non-severe asthma. Published treatable traits were mapped to
      registry data fields and their prevalence was described. Participants were
      characterized at baseline and every 6 months for 24 months. RESULTS: In SAWD, 24
      treatable traits were identified in three domains: pulmonary, extrapulmonary and
      behavioural/risk factors. Patients with severe asthma expressed more pulmonary
      and extrapulmonary treatable traits than non-severe asthma. Allergic
      sensitization, upper-airway disease, airflow limitation, eosinophilic
      inflammation and frequent exacerbations were common in severe asthma. Ten traits
      predicted exacerbation risk; among the strongest were being prone to
      exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction
      and obstructive sleep apnoea. CONCLUSION: Treatable traits can be assessed using
      a severe asthma registry. In severe asthma, patients express more treatable
      traits than non-severe asthma. Traits may be associated with future asthma
      exacerbation risk demonstrating the clinical utility of assessing treatable
      traits.

PMID- 30230141
TI  - How can nurses reclaim the inpatient research agenda?

PMID- 30230140
TI  - Sera with anti-enteric neuronal antibodies from patients with irritable bowel
      syndrome promote apoptosis in myenteric neurons of guinea pigs and human SH-Sy5Y
      cells.
AB  - BACKGROUND: Sera anti-enteric neuronal antibodies (AENA), neuronal inflammation,
      and degeneration in myenteric plexus in patients with irritable bowel syndrome
      (IBS) were reported. Effects of sera AENA in patients with IBS are unclear.
      METHODS: Patients with IBS met Rome III criteria were enrolled. Controls included
      healthy subjects (HS) and patients with slow transit functional constipation,
      inflammatory bowel disease, chronic intestinal pseudo-obstruction, and autoimmune
      diseases. Indirect immunofluorescence was used to detect AENA. Anti-enteric
      neuronal antibodies intensities were termed as "1" = weak fluorescence (mild
      positive); "2" = moderate fluorescence (moderate positive); "3" = very high
      fluorescence (intensive positive). Intensities of >=1 were defined as positive
      and >=2 were defined as obvious positive. Cultured myenteric neurons of small
      intestine from guinea pigs and human SH-Sy5Y cells were incubated with fetal
      bovine serum (FBS), HS sera, or IBS sera with or without AENA. Indirect
      immunofluorescence with anti-PGP9.5/DAPI/anti-active caspase-3 or TUNEL, Western
      blot, and flow cytometry were used to detect apoptosis. KEY RESULTS: Overall, 293
      patients with IBS were enrolled (41.7 +/- 11.5 years). AENA-positive and obvious
      positive rates in IBS were higher than HS (76.8% vs 33%; 43.7% vs 7%; all P <
      0.001). Myenteric neurons incubated with AENA moderate or intensive positive IBS
      sera showed higher rates of anti-active caspase-3 and TUNEL-positive cells than
      HS or FBS (20% +/- 7.3% and 35% +/- 13.3% vs 4.3% +/- 1.5% and 0.9% +/- 0.4%,
      respectively; 6.2% +/- 2.0% and 10.2% +/- 4.6% vs 1.3% +/- 1.9% and 0.5%+/-0.5%,
      respectively; all P < 0.05). Human SH-Sy5Y cells incubated with AENA moderate or
      intensive positive IBS sera showed increased cleaved caspase-3 and Bax expression
      and decreased Bcl-2 expression. Flow cytometry showed apoptosis rates of these
      two groups were higher than that of AENA mild positive, negative, HS, and FBS
      (7.6%+/-0.8% and 10.7%+/-1.3% vs 5.0%+/-0.8%, 3.8%+/-0.3%, 3.4%+/-0.2% and,
      2.8%+/-0.2%, P < 0.05). CONCLUSIONS AND INFERENCES: The AENA obvious positive
      rate in patients with IBS was higher than HS, and sera with higher levels of AENA
      promoted neuronal apoptosis. AENA-mediated neuropathy might exist in a subset of
      patients with IBS.

PMID- 30230142
TI  - Partial breast irradiation for ductal carcinoma in situ: The Goldilocks
      principle?

PMID- 30230143
TI  - Physical therapy practice in intensive care units in Jordanian hospitals: A
      national survey.
AB  - OBJECTIVE: A national survey was conducted to determine the current status of
      physical therapy practice in the intensive care units (ICUs) of Jordanian
      hospitals. METHODS: An online survey was sent via email to physical therapists
      working at Jordanian hospitals. Questions of the survey addressed the physical
      therapy demographics, staffing, education, training, and barriers of practice.
      The responses were compared among four different hospital sectors in the country.
      RESULTS: The response rate was 31% (50/161). Thirty-six percent of participants
      had more than 10 years of experience in physical therapy, and 26% had less than 1
      year of experience in the intensive care practice. Staffing of physical
      therapists working in ICUs relative to the total ICU beds was the highest in
      public hospitals compared with other hospital sectors. Among all participants,
      only 4% had received specialized postgraduate ICU training. The barriers to ICU
      physical therapy practice in Jordan included insufficient staffing, inadequate
      training, and lack of understanding of physical therapy role for ICU patients.
      CONCLUSION: The study showed the main barriers to ICU physical therapy practice
      in Jordan. There is a need for well-structured strategies to overcome these
      barriers to help improve the delivery of physical therapy services in Jordan.

PMID- 30230145
TI  - Manual removal of placenta in women having unpredictable adherent placenta.
AB  - AIM: Our aim is to provide expected outcomes for undergoing manual removal of
      placenta (MROP) following vaginal delivery in women having an unpredictable
      adherent placenta (AP). METHODS: The data were obtained from four hospitals in
      Miyazaki Prefecture, Japan. We used propensity score-matched (1:1) analysis to
      match women who underwent MROP with women who did not undergo MROP (control).
      Total blood loss and hemorrhagic rate used as a ratio of women who reached a
      certain amount of blood loss were compared. Subgroup analysis was undertaken and
      was dependent on the presence of AP. We found the cut-off value of blood loss for
      detecting AP. RESULTS: Thirty-seven MROP cases were identified. Total blood loss
      and hemorrhagic rate differed significantly between MROP cases and controls; 95%
      of controls had blood loss of 1000 mL or less, whereas for the MROP cases, it was
      14%. Fourteen MROP cases were diagnosed with AP. The hemorrhagic rate differed
      significantly between MROP cases with and without AP (n = 19); 79% of MROP cases
      without AP had blood loss of 2000 mL or less, whereas for the MROP cases with AP,
      it was 7%. There were seven incidents of hysterectomy and two of arterial
      embolization in MROP cases with AP. Through receiver operating characteristic
      curve analysis, 2035 mL of blood loss was determined to be the optimal cut-off
      value for detecting AP. CONCLUSION: The incidence of unpredictable AP in MROP
      cases was as high as 38%. The morbidity of MROP cases with unpredictable AP was
      severe. MROP should be prohibited in the absence of appropriate hemostatic
      preparations.

PMID- 30230144
TI  - Molecular docking and two-dimensional quantitative structure-activity
      relationship studies of synthetic flavonoids on horseradish peroxidase compounds
      (I, II, and III).
AB  - For the first time, the enzymatic inhibition activity of 13 synthetic flavonoids
      was assessed by quantitative structure-activity relationship (QSAR) modeling and
      molecular docking with the three states of the enzyme horseradish peroxidase
      (HRP). The results show that apigenin, quercetin, kaempferol, fisetin, tricetin,
      and luteolin exerted a high competitive inhibition on HRP (Ki between 0.14 and
      1.74 mM) compared with other flavonoids. The QSAR model of enzymatic activity (R2
      = 0.95, RMSE = 5.48) showed that Ghose-Crippen octanol-water partition
      coefficient (Alog P) and lowest unoccupied molecular orbital's energy
      (epsilonlumo ) correlated with 0.65 and 0.17, respectively, with Ki values.
      According to the docking results using Molegro Virtual Docker program, all the
      flavonoids have shown great binding affinity towards peroxidase. Apigenin has the
      largest MolDock score in the three states of HRP noting an increased affinity of
      these flavonoids between compound I and compound II by 2.26%. However, these
      affinities strongly decrease between compound II and compound III by 28.43%
      especially for luteolin whose MolDock score decreased by 74.7%. With the results
      of docking, the affinities of the flavonoids tested and translated by their Ki
      values are much more presentative of the inhibition of the first reaction states
      of HRP because their inhibitory effect is important.

PMID- 30230146
TI  - Ten-year retrospective review of the incidence of serious infections in patients
      on biologic disease modifying agents for rheumatoid arthritis in three tertiary
      hospitals in Western Australia.
AB  - INTRODUCTION: Biologic disease modifying anti rheumatic drugs (bDMARDs) have
      significantly improved the prognosis for patients with Rheumatoid Arthritis (RA).
      However, due to their immunosuppressive nature, concerns remain about the
      potential for infection in patients receiving these medications. AIMS: The aim of
      this review is to evaluate the incidence of serious infections (SI) in a Western
      Australian cohort of patients with RA who are receiving bDMARDs. The role of
      confounders including age, gender, co-morbidities and use of glucocorticoids was
      also evaluated. The incidence of SI was defined as any infection necessitating
      admission to the hospital and the use of antibiotics METHODS: A ten-year
      retrospective review was conducted of all patients with RA who were receiving
      bDMARDs at three tertiary hospitals in Western Australia (WA). Discharge
      summaries and all available clinic letters were reviewed and patient demographics
      and clinical data was collected. Pearson chi-squared test and student's t-test
      were used for comparing demographic factors and clinical variables between the
      groups with SI and those without. RESULTS: 102 patients met the inclusion
      criteria for the period 2006 - 2016, 25 of whom had been admitted with SI,
      accounting for a total of 46 admissions. Skin and soft tissue infections were the
      most common (28%) followed by respiratory infections (26%) and urinary tract
      infections (20%). The incidence rate of SI was 8.98 per 100 person years. The
      rate was lowest with adalimumab (5.27 per 100 person years) and highest with
      infliximab (34.5 per 100 person years). Those with SI were older (68 years vs 60
      years; p = 0.02) and had been on bDMARDs for longer period of time (6.05 years vs
      4.68 years; p = 0.04). There was no significant increase in length of stay due to
      co-administration of glucocorticoids. The presence of co-morbidities did not play
      a significant role in increasing the risk of SI. CONCLUSION: Age and duration of
      bDMARD use were statistically significant factors associated with an increased
      risk of SI. Co-morbidities did not play a significant role in increasing the
      incidence of SI. Patients who were on both glucocorticoids and bDMARDs did not
      have a significant increase in length of stay when compared with patients who
      were just on bDMARDs. More research is needed in this area with larger numbers to
      draw statistically significant conclusions regarding the role of co-morbidities
      in SI risk and the individual infection risk associated with each bDMARD. This
      article is protected by copyright. All rights reserved.

PMID- 30230147
TI  - Palladium/Graphitic Carbon Nitride (g-C3 N4 ) Stabilized Emulsion Microreactor as
      a Store for Hydrogen from Ammonia Borane for Use in Alkene Hydrogenation.
AB  - Direct hydrogenation of C=C double bonds is a basic transformation in organic
      chemistry which is vanishing from simple practice because of the need for
      pressurized hydrogen. Ammonia borane (AB) has emerged as a hydrogen source
      through its safety and high hydrogen content. However, in conventional systems
      the hydrogen liberated from the high-cost AB cannot be fully utilized. Herein, we
      develop a novel Pd/g-C3 N4 stabilized Pickering emulsion microreactor, in which
      alkenes are hydrogenated in the oil phase with hydrogen originating from AB in
      the water phase, catalysed by the Pd nanoparticles at the interfaces. This
      approach is advantageous for more economical hydrogen utilization over
      conventional systems. The emulsion microreactor can be applied to a range of
      alkene substrates, with the conversion rates achieving >95 % by a simple
      modification.

PMID- 30230148
TI  - The impact of preoperative anaemia and anaemic subtype on patient outcome in
      colorectal cancer.
AB  - AIM: Preoperative anaemia is associated with adverse outcomes in colorectal
      cancer (CRC). To clarify the reason for this we aimed to comprehensively assess
      the association of preoperative anaemia with tumour characteristics, host
      systemic inflammation and nutrition status, and perioperative blood transfusion.
      METHOD: We used an integrated database of 592 CRC patients. The association of
      preoperative anaemic subtype, calculated from haemoglobin and erythrocyte mean
      corpuscular volume levels, with patient outcome, preoperative serum data relating
      to systemic inflammation and nutrition and perioperative blood transfusion was
      analysed. RESULTS: Preoperative anaemia was significantly associated with poorer
      overall survival and relapse-free survival (RFS); in particular microcytic
      anaemia had a trend to poorer RFS than other forms of anaemia (P = 0.0648). In
      addition, preoperative anaemia was significantly correlated with right-sided
      tumours, greater depth of tumour invasion, use of neoadjuvant chemotherapy,
      poorer prognostic nutritional index and higher modified Glasgow Prognostic Score
      (mGPS). Microcytic anaemia in particular had a strong association with a greater
      depth of tumour invasion (P = 0.0072) and higher mGPS (P = 0.0058) than other
      causes of anaemia. Perioperative blood transfusion for CRC patients with anaemia
      was associated with adverse outcomes. CONCLUSIONS: Preoperative anaemia,
      especially microcytic anaemia, was associated with poor patient outcomes,
      possibly due to poor systemic inflammatory and nutritional status, and it was not
      improved by perioperative blood transfusion. Our data suggest that preoperative
      anaemia and the anaemic subtype may serve as an easily available predictor of
      outcome in CRC.

PMID- 30230150
TI  - Simple Alkaline-Earth Metal Catalysts for Effective Alkene Hydrogenation.
AB  - Alkaline earth metal amides (AeN''2 : Ae=Ca, Sr, Ba, N''=N(SiMe3 )2 ) catalyze
      alkene hydrogenation (80-120  degrees C, 1-6 bar H2 , 1-10 mol % cat.), with the
      activity increasing with metal size. Various activated C=C bonds (styrene, p-MeO
      styrene, alpha-Me-styrene, Ph2 C=CH2 , trans-stilbene, cyclohexadiene, 1-Ph
      cyclohexene), semi-activated C=C bonds (Me3 SiCH=CH2 , norbornadiene), or non
      activated (isolated) C=C bonds (norbornene, 4-vinylcyclohexene, 1-hexene) could
      be reduced. The results show that neutral Ca or Ba catalysts are active in the
      challenging hydrogenation of isolated double bonds. For activated alkenes (e.g.
      styrene), polymerization is fully suppressed due to fast protonation of the
      highly reactive benzyl intermediate by N''H (formed in the catalyst initiation).
      Using cyclohexadiene as the H source, the first Ae metal catalyzed H-transfer
      hydrogenation is reported. DFT calculations on styrene hydrogenation using CaN''2
      show that styrene oligomerization competes with styrene hydrogenation.
      Calculations also show that protonation of the benzylcalcium intermediate with
      N''H is a low-energy escape route, thus avoiding oligomerization.

PMID- 30230149
TI  - Electrophilic Phosphonium Cation-Mediated Phosphane Oxide Reduction Using Oxalyl
      Chloride and Hydrogen.
AB  - The metal-free reduction of phosphane oxides with molecular hydrogen (H2 ) using
      oxalyl chloride as activating agent was achieved. Quantum-mechanical
      investigations support the heterolytic splitting of H2 by the in situ formed
      electrophilic phosphonium cation (EPC) and phosphane oxide and subsequent
      barrierless conversion to the phosphane and HCl. The reaction can also be
      catalyzed by the frustrated Lewis pair (FLP) consisting of B(2,6-F2 C6 H3 )3 and
      2,6-lutidine or phosphane oxide as Lewis base. This novel reduction was
      demonstrated for triaryl and diaryl phosphane oxides providing access to
      phosphanes in good to excellent yields (51-93 %).

PMID- 30230151
TI  - Outcomes of an initiative to improve inpatient safety of small bore thoracostomy
      tube insertion.
AB  - BACKGROUND: Intercostal chest catheter (ICC) insertion is a common hospital
      procedure with attendant risks including life-threatening complications such as
      pneumothorax and visceral damage. OBJECTIVE: To investigate the effect of a
      quality improvement initiative on complications associated with inpatient
      thoracostomy tube insertion. METHODS: Following an audit of ICC complications in
      inpatients over a 2 year period we implemented a comprehensive quality
      improvement (QI) program. This involved, formal training in and mandatory use of
      thoracic ultrasound, standardization of the procedure and documentation, a
      dedicated procedure room with nurses trained in assisting ICC insertion, and
      senior supervision for medical staff. An audit over 2 years post implementation
      of the QI protocol was compared with pre-implementation results. RESULTS: 103
      cases were reviewed pre- and 105 cases were reviewed post-implementation of the
      QI program. All procedures following the QI initiative were image guided compared
      to 23.3% of cases pre-implementation. The rate of developing a pneumothorax
      requiring intervention post-implementation was less than pre-implementation (1.9%
      vs 5.8% (p=0.023). Post implementation, there were no instances of dry taps,
      viscera perforation, clinically significant bleeding or wrong side ICC insertion
      and documentation improved. CONCLUSIONS: A quality improvement initiative applied
      to thoracostomy tube insertion in hospital inpatients can reduce complications
      and improve procedure documentation. This article is protected by copyright. All
      rights reserved.

PMID- 30230152
TI  - Acneiform eruptions: An unusual dermatological side effect of ribavirin.

PMID- 30230153
TI  - End-stage kidney disease in Fiji.
AB  - BACKGROUND: Chronic kidney disease is now a leading cause of death in Fiji. The
      country lacks even basic statistics about the incidence of end stage kidney
      disease (ESKD) and presents significant challenges to conducting clinical
      research. AIM: To estimate the incidence and characteristics of ESKD in Fijian
      adults. METHODS: A retrospective cohort study was conducted of patients admitted
      to Colonial War Memorial Hospital in Suva, Fiji in 2012. Suspected ESKD cases
      were identified from laboratory registers of renal function tests and confirmed
      through medical record review. Population data were from the Fijian Bureau of
      Statistics. RESULTS: Screening identified 1474 suspected ESKD cases. Following
      removal of 763 duplicates and cases with discrepant identifiers, 711 unique cases
      remained. An additional 552 cases met exclusion criteria including acute kidney
      injury (247), failure to be admitted (131), and pre-existing ESKD diagnosis
      (103), leaving 159 cases of confirmed ESKD. Median age was 57 years (IQR 47-65).
      Crude and age-adjusted ESKD incidence rates were 753 per million population (pmp)
      (95% CI 636-870) and 793 pmp (95% CI 669-916) respectively, rising to 938 pmp
      (95% CI 804-1072) if African-American correction was removed. Diabetic
      nephropathy was the most common cause of ESKD (65.4%). CONCLUSIONS: The incidence
      of ESKD in Fiji is high. This is a substantial public health problem that is
      likely impacting life expectancy and quality of life. Improving screening,
      detection and management of kidney disease should be given more prominence in
      programs to address non-communicable diseases in Fiji and the Western Pacific.
      This article is protected by copyright. All rights reserved.

PMID- 30230154
TI  - Breeding new varieties for controlled environments.
AB  - Agricultural production in controlled environments is increasingly feasible, and
      may play an important role in providing nutrition and choice to growing urban
      centres. New technologies in lighting, ventilation, robotics and irrigation are
      just a few of the innovations that enable production of high-value specialty
      crops outside of a traditional field setting. However, despite all of the
      advances in the hardware within the plant factory operation, innovation of the
      most complex machine has been neglected - the plant itself. Indoor agricultural
      operations typically rely on legacy varieties, plants selected and bred for field
      conditions. In the field, phenotypic stability is paramount, as production must
      be consistent in an unpredictable and changing environment. However, the
      controlled environment affords focus on different breeding priorities as
      environmental flux, pests, pathogens and post-harvest quality are less formidable
      barriers to production. On the contrary, breeding for controlled environments
      shifts the focus to a completely different set of plant traits, such as rapid
      growth, performance in low light environments and active manipulation of plant
      stature. Instead of breeding for phenotypic stability, plants may be bred to
      maximise genetic plasticity, allowing specific traits to be presented as a
      function of the quality of the ambient light spectrum. In this scenario plant
      varieties may be grown with optimal size, supporting a focus on consumer traits
      like flavour or accumulation of health-related compounds. Gene editing may be a
      central technology in the production of designer plants for controlled
      environments. This review considers the opportunity for breeding for controlled
      environments, with a focus on a revision of priorities for controlled-environment
      breeders.

PMID- 30230155
TI  - Genetic structure of the Canarian palm tree (Phoenix canariensis) at the island
      scale: does the 'island within islands' concept apply to species with high
      colonisation ability?
AB  - Oceanic islands are dynamic settings that often promote within-island patterns of
      strong population differentiation. Species with high colonisation abilities,
      however, are less likely to be affected by genetic barriers, but island size may
      impact on species genetic structure regardless of dispersal ability. The aim of
      the present study was to identify the patterns and factors responsible for the
      structure of genetic diversity at the island scale in Phoenix canariensis, a palm
      species with high dispersal potential. To this end, we conducted extensive
      population sampling on the three Canary Islands where the species is more
      abundant and assessed patterns of genetic variation at eight microsatellite loci,
      considering different within-island scales. Our analyses revealed significant
      genetic structure on each of the three islands analysed, but the patterns and
      level of structure differed greatly among islands. Thus, genetic differentiation
      fitted an isolation-by-distance pattern on islands with high population densities
      (La Gomera and Gran Canaria), but such a pattern was not found on Tenerife due to
      strong isolation between colonised areas. In addition, we found a positive
      correlation between population geographic isolation and fine-scale genetic
      structure. This study highlights that island size is not necessarily a factor
      causing strong population differentiation on large islands, whereas high
      colonisation ability does not always promote genetic connectivity among
      neighbouring populations. The spatial distribution of populations (i.e. landscape
      occupancy) can thus be a more important driver of plant genetic structure than
      other island, or species' life-history attributes.

PMID- 30230157
TI  - Metastatic pattern and new primary tumours after neoadjuvant therapy and surgery
      in rectal cancer.
AB  - AIM: Current follow-up guidelines for distant tumour recurrence after rectal
      cancer surgery are not defined or agreed. The aim was to elucidate the pattern of
      recurrence over time and provide information that could help direct a strategy
      for surveillance. METHOD: In all, 378 patients with locally advanced rectal
      cancer were treated with preoperative chemoradiotherapy and surgery with curative
      intent. Patients were followed up with a standard protocol, and data were
      prospectively collected in a dedicated database. Disease-free survival and
      overall survival were calculated. RESULTS: Within a median follow-up time of 75
      months, rates of local and distant recurrence were 2.6% and 21.7%, respectively.
      Risk factors for recurrence were a baseline carcinoembryonic antigen > 5.0 ng/ml,
      a distance from the anal verge <= 5 cm, R1 resection margins, G3 grading, ypT
      staging > 2, positive lymph node status and a tumour regression grade of 3-5.
      Disease-free survival did not vary significantly between patients with lung and
      extra-pulmonary metastases (P = 0.59). The only factor associated with increased
      risk of lung metastases was a distance of the tumour from the anal verge of <= 5
      cm (P = 0.01). Most recurrences occurred within the first 3 years after surgery
      (74.4%). The first site of recurrence was most frequently the lung (52.0%). The
      most frequent new primary malignancy was lung cancer (22.5%). CONCLUSIONS:
      Patients undergoing curative therapy for rectal cancer often experience distant
      recurrence; the majority of recurrences occur within the first 3 years after
      surgery and lung metastases are the most common. A predictive factor for
      pulmonary recurrence is a tumour in the lower rectum.

PMID- 30230156
TI  - Front-line management of non-Hodgkin lymphoma in Australia. Part 1: follicular
      lymphoma.
AB  - Outcomes with follicular lymphoma (FL) have improved in the modern era and median
      survival is now beyond 15 years. Therapeutic decisions need to consider this
      increased survival as well as recent clinical trial data and emerging treatments.
      In this context, we present here current approaches to front-line management of
      FL in Australia. Treatment choices depend on the disease stage, tumour burden,
      the patient's age, symptoms, comorbidities and preferences. Only about 10-15% of
      patients with FL are diagnosed with early stage disease. For patients with low
      grade, early stage disease, radiotherapy is recommended. The addition of
      chemotherapy has been shown to increase progression free survival (PFS) but
      without demonstrated overall survival advantage. For patients with low tumour
      burden advanced stage FL, immediate treatment may not be required, and we
      recommend considering active monitoring. For stage III/IV disease that is
      symptomatic and/or with high tumour burden, established first-line treatment is
      chemotherapy in combination with rituximab, often followed by rituximab
      maintenance. The listing of bendamustine on the Pharmaceutical Benefits Scheme
      has expanded the first-line treatment options in Australia to include
      bendamustine in combination with rituximab for patients with Grade 1-2 disease.
      In the FL subgroup of the StiL trial, therapy with bendamustine plus rituximab
      significantly increased PFS compared with rituximab in combination with
      cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), without
      rituximab maintenance. Initial tolerability may be more favourable with
      bendamustine than other therapies overall, but clinical vigilance is still
      required because of concerns of late infectious toxicities associated with
      prolonged T-cell depletion. This article is protected by copyright. All rights
      reserved.

PMID- 30230158
TI  - Tuning Intramolecular Forster Resonance Energy Transfer and Activating
      Intramolecular Singlet Fission.
AB  - The synergy of panchromatic absorption throughout most of the visible range of
      the solar spectrum and intramolecular singlet fission (SF) has been realized in a
      series of conjugates featuring different light-harvesting subphthalocyanines
      (SubPcs) and an energy accepting pentacene dimer (Pnc2 ). At the focal point was
      a modular SubPc approach, which was based on decorating the SubPc core with
      different peripheral substituents to tailor and fine-tune their optical
      properties. Transient absorption measurements assisted in corroborating that the
      SubPcs act as energy-transfer antennas by means of unidirectional and
      quantitative intramolecular Forster resonance energy transfer (FRET) to the Pnc2
      , where an intramolecular SF affords triplet quantum yields reaching unity.

PMID- 30230159
TI  - Temporal scale of environmental correlations affects ecological synchrony.
AB  - Population densities of a species measured in different locations are often
      correlated over time, a phenomenon referred to as synchrony. Synchrony results
      from dispersal of individuals among locations and spatially correlated
      environmental variation, among other causes. Synchrony is often measured by a
      correlation coefficient. However, synchrony can vary with timescale. We
      demonstrate theoretically and experimentally that the timescale-specificity of
      environmental correlation affects the overall magnitude and timescale-specificity
      of synchrony, and that these effects are modified by population dispersal. Our
      laboratory experiments linked populations of flour beetles by changes in habitat
      size and dispersal. Linear filter theory, applied to a metapopulation model for
      the experimental system, predicted the observed timescale-specific effects. The
      timescales at which environmental covariation occurs can affect the population
      dynamics of species in fragmented habitats.

PMID- 30230160
TI  - Inflammatory bowel disease incidence, prevalence and twelve-month initial disease
      course in Tasmania, Australia.
AB  - BACKGROUND: High inflammatory bowel disease (IBD) rates have been reported in
      Australasia, but no state-wide studies have yet been performed. AIMS: This study
      estimates the one-year incidence and point prevalence of IBD in the state of
      Tasmania, Australia. It also reports clinical outcomes after twelve months of
      diagnosis in an incident cohort. METHODS: A prospective, population-based study
      was performed collecting prevalent and incident state-wide cases from 1st June
      2013 to 31st May 2014. Case data were identified from specialist doctors,
      pathology databases and hospital records. Age-standardised rates (ASRs) were
      calculated based on World Health Organization 2000 standard population
      characteristics. Incident cases were followed up twelve months after diagnosis.
      RESULTS: There were 1719 prevalent cases: ASRs for IBD, Crohn's disease (CD),
      ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBDU)
      prevalence were 303.9, 165.5, 131.4 and 6.9 per 100,000 respectively. Prevalent
      CD cases were younger, with greater immunomodulator/biologic use and bowel
      resections. There were 149 incident cases: ASRs for IBD, CD, UC and IBDU
      incidence were 29.5, 15.4, 12.4, and 1.7 per 100,000 respectively. Incident CD
      cases were more likely than UC or IBDU to require escalation of medical therapy,
      hospitalisation, and bowel resection especially among those with penetrating or
      stricturing disease. They had longer duration of symptoms prior to diagnosis.
      CONCLUSIONS: IBD prevalence and incidence rates are high in Tasmania, comparable
      to data from other Australasian studies and those from Northern Europe and
      America. Poorer twelve month clinical outcomes occurred in complicated CD, with
      greater use of healthcare resources. This article is protected by copyright. All
      rights reserved.

PMID- 30230161
TI  - Effects of early introduction of non-invasive positive pressure ventilation based
      on forced vital capacity rate of change: Variation across amyotrophic lateral
      sclerosis clinical phenotypes.
AB  - PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
      associated with high morbidity and mortality. We evaluated the ability of
      pulmonary function tests to predict disease progression by ALS clinical
      phenotypes, and the timing of the introduction of non-invasive positive pressure
      ventilation (NIPPV). MATERIALS AND METHODS: A cohort study was performed in all
      adult patients who fulfilled El Escorial criteria at a tertiary-care academic
      medical centre for veterans in the USA from 1 January 2010 to 31 December 2014.
      Eligible patients underwent sitting and supine forced vital capacity (FVC) and
      the FVC rate of change (RoC) per month was calculated. ALS Functional Rating
      Scale-Revised (ALSFRS-R) scores were collected. RESULTS: A total of 137 patients
      were included in our analysis. The average survival from ALS onset was 31.40 (+/
      40.04) months. The general cohort median (IQR) RoC was -0.87 (-2.55 to 0.34)/
      0.65 (-2.55 to 0.70) % per month (P = 0.81) of the sitting/supine FVC,
      respectively. However, mean monthly RoC varied among the ALS phenotypes, with
      higher variation among global ALS, where greater decline in RoC was noted. The
      average time from ALS onset to tracheostomy was 27.88 (+/-22.21) months. The
      average sitting/supine FVC RoC for subjects requiring tracheostomy was -2.86 (+/
      3.77)/-3.63 (+/-3.75) at the time of tracheostomy, compared to -1.190 (+/-2.38)/
      1.07 (+/-3.78) for those who did not require the procedure. Although NIPPV use
      did not result in statistically significant improvements in either the sitting or
      supine FVC %, it did slow the RoC decline of patients with global ALS phenotypes.
      CONCLUSIONS: Initiation of NIPPV based on decline in RoC rather than the absolute
      value of either sitting or supine FVC may result in early stabilisation of ALS
      patients' pulmonary deterioration for the global clinical phenotype, and thus may
      have the potential for prolonging survival until tracheostomy or death.

PMID- 30230162
TI  - When side effect becomes the effect: Efficacy of capecitabine in refractory
      psoriasis.

PMID- 30230163
TI  - Feasibility of all-in-one venoplasty with venous cuff using opened round ligament
      for right lobe graft in living donor liver transplantation.
AB  - Various hepatic vein reconstruction techniques using such as autologous inferior
      vena cava (IVC) patch grafts, internal jugular vein (IJV), saphenous vein,
      explanted portal vein (EPV), homologous cryopreserved vein grafts, and prosthetic
      vascular grafts have been reported to overcome primary graft dysfunction or small
      for-size graft syndrome in living donor liver transplantation (LDLT) using right
      lobe (RL) graft without middle hepatic vein (MHV) trunk This article is protected
      by copyright. All rights reserved.

PMID- 30230164
TI  - Overweight and obesity as major, modifiable risk factors for urinary incontinence
      in young to mid-aged women: a systematic review and meta-analysis.
AB  - The purpose of this review and meta-analysis was to evaluate overweight and
      obesity as risk factors for urinary incontinence in young to mid-aged women.
      Understanding these relationships during this life stage is important as early
      onset increases the risk for developing severe and persistent incontinence. A
      systematic search resulted in 497 citations, 14 of which were retained for
      review. Data were analysed by overweight and obesity and by subtype of urinary
      incontinence - stress, urge, mixed and severe. When compared with 'normal' body
      mass index, overweight was associated with a one-third increase in risk of
      urinary incontinence (relative risk = 1.35, 95% confidence interval = 1.20-1.53),
      while the risk was doubled in women with obesity (relative risk = 1.95, 95%
      confidence interval = 1.58-2.42). When estimates were pooled according to urinary
      incontinence subtype, there was no statistical difference in risk. Overweight and
      obesity are strong predictors of urinary incontinence, with a significantly
      greater risk observed for obesity. Clinical advice to young women at risk of, or
      presenting with, obesity should not be limited to metabolic health only but
      should emphasize the role of excess weight on pelvic floor weakening and
      subsequent risk of incontinence.

PMID- 30230165
TI  - Functional Imaging with Nucleic-Acid-Based Sensors: Technology, Application and
      Future Healthcare Prospects.
AB  - Timely monitoring and assessment of human health plays a crucial role in
      maintaining the wellbeing of our advancing society. In addition to medical tools
      and devices, suitable probe agents are crucial to assist such monitoring, either
      in passive or active ways (i.e., sensors) through inducible signals. In this
      review we highlight recent developments in activatable optical sensors based on
      nucleic acids. Sensing mechanisms and bio-applications of these nucleic acid
      sensors in ex vivo assays, intracellular or in vivo settings are described. In
      addition, we discuss the limitations of these sensors and how nanotechnology can
      complement/enhance sensor properties to promote translation into clinical
      applications.

PMID- 30230166
TI  - A twisted tale.

PMID- 30230167
TI  - Meeting guideline recommendations for vaccination: Can we get there from here?

PMID- 30230168
TI  - Development and evaluation of novel salt-tolerant Eucalyptus trees by molecular
      breeding using an RNA-Binding-Protein gene derived from common ice plant
      (Mesembryanthemum crystallinum L.).
AB  - The breeding of plantation forestry trees for the possible afforestation of
      marginal land would be one approach to addressing global warming issues. Here, we
      developed novel transgenic Eucalyptus trees (Eucalyptus camaldulensis Dehnh.)
      harbouring an RNA-Binding-Protein (McRBP) gene derived from a halophyte plant,
      common ice plant (Mesembryanthemum crystallinum L.). We conducted screened-house
      trials of the transgenic Eucalyptus using two different stringency salinity
      stress conditions to evaluate the plants' acute and chronic salt stress
      tolerances. Treatment with 400 mM NaCl, as the high-stringency salinity stress,
      resulted in soil electrical conductivity (EC) levels >20 mS/cm within 4 weeks.
      With the 400 mM NaCl treatment, >70% of the transgenic plants were intact,
      whereas >40% of the non-transgenic plants were withered. Treatment with 70 mM
      NaCl, as the moderate-stringency salinity stress, resulted in soil EC levels of
      approx. 9 mS/cm after 2 months, and these salinity levels were maintained for the
      next 4 months. All plants regardless of transgenic or non-transgenic status
      survived the 70 mM NaCl treatment, but after 6-month treatment the transgenic
      plants showed significantly higher growth and quantum yield of photosynthesis
      levels compared to the non-transgenic plants. In addition, the salt accumulation
      in the leaves of the transgenic plants was 30% lower than that of non-transgenic
      plants after 15-week moderate salt stress treatment. There results suggest that
      McRBP expression in the transgenic Eucalyptus enhances their salt tolerance both
      acutely and chronically.

PMID- 30230169
TI  - Population recovery of a common vole population (Microtus arvalis) after
      population collapse.
AB  - BACKGROUND: Population collapses in small mammals occur naturally after natural
      disasters and during multi-annual population fluctuations as well as after man
      made intervention such as rodent management action. Although there has been
      extensive previous work on patterns and mechanisms of population fluctuations and
      cyclicity, little is known about population recovery after collapse. In Europe,
      the common vole (Microtus arvalis) is the major pest species in agriculture,
      damaging crops, competing with livestock and potentially posing a health risk to
      people. In this study, we investigated population recovery, recovery mechanism
      and recovery time of common vole populations after artificially inducing a
      collapse through rodenticide application. RESULTS: The rodenticide treatment
      reduced abundance in spring (by about 90%) but not in summer. Demographic data
      (age, sex-ratio, breeding activity) suggest that it was mostly immigration and
      not reproduction that led to population recovery after collapse. CONCLUSIONS: The
      findings indicate that rodenticide treatment should be conducted in spring before
      the main reproductive season starts. The treatment effect was transient and
      lasted for about 3 months before immigration offset the initial reduction in
      population abundance. This indicates that immigration patterns should be
      considered by managing vole populations at an appropriate spatial scale and
      frequency to prevent rapid repopulation. (c) 2018 Society of Chemical Industry.

PMID- 30230171
TI  - Central nervous system manifestations of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is a neurocutaneous autosomal-dominant genetic
      syndrome marked by development of hamartomatous lesions arising from dysfunction
      of the mammalian target of rapamycin (mTOR) pathway. Although TSC remains a
      heterogeneous clinical entity, the recent inclusion of genetic diagnostic
      criteria reflects advancement in our understanding of its underlying
      etiopathogenesis. Abnormal cellular growth, differentiation, and migration result
      in multisystem sequelae, with neurologic manifestations of TSC representing the
      primary cause of morbidity and mortality for the majority of individuals. Modern
      imaging techniques aid in the diagnosis of TSC and guide treatment strategies by
      revealing central nervous system findings. Cortical tubers are the namesake
      lesion of the disorder and occur in up to 90% of cases, often exerting
      significant epileptogenic potential. Subependymal nodules are found in 80% of
      patients as calcified tumors lining the ependyma of the lateral ventricles. In
      some cases, these nodules are thought to progress to subependymal giant cell
      astrocytomas and may present with obstructive hydrocephalus. Retinal astrocytic
      hamartomas are also common, present in 50% of patients. Surgery remains the
      treatment of choice for large or symptomatic lesions, though clinical trials have
      highlighted a potential role for mTOR pathway antagonism. A multidisciplinary
      approach is necessary for achieving optimal patient outcomes.

PMID- 30230170
TI  - Predicting falls from behavioral and psychological symptoms of dementia in older
      people residing in facilities.
AB  - AIM: The aim of the present study was to examine whether behavioral and
      psychological symptoms of dementia at the time of admission could be a predictor
      of falls in older people with dementia residing in geriatric health service
      facilities. METHODS: Three geriatric health services facilities located in
      Fukushima Prefecture, Japan, were the targeted facilities. Of the 305 people
      admitted between May 2013 and November 2014, 242 (74 men, 168 women) who scored
      <=20 points on the Hasegawa Dementia Scale-Revised were targeted for analysis. A
      total of 15 items from the Long-term Care Certification Questionnaire Group 4
      were used to assess behavioral and psychological symptoms of dementia, and were
      compared by the presence or absence of falls. RESULTS: Of the 242 participants,
      153 were non-fallers and 89 were fallers. After adjusting for sex, age, Revised
      Hasegawa Dementia Scale-Revised, degree of care (which showed a significant
      relationship with falls in univariate analysis), activities of daily living and
      history of falls, the influence of behavioral and psychological symptoms of
      dementia on falls was examined, and showed a significant association with falls
      and a significant increase of hazard ratio for the behavioral symptoms
      "wandering" 2.23 (95% confidence interval 1.35-3.68) and "agitation" 1.94 (95%
      confidence interval 1.24-3.04). CONCLUSIONS: Because the risk of falling is high
      for residents who at the time of admission have the behavioral and psychological
      symptoms of dementia of "wandering" and "agitation," it is necessary to predict
      the possibility of falling at an early stage, monitor the residents and adjust
      the environment. Geriatr Gerontol Int 2018; 18: 1573-1577.

PMID- 30230172
TI  - Is metformin still the most efficacious first-line oral hypoglycaemic drug in
      treating type 2 diabetes? A network meta-analysis of randomized controlled
      trials.
AB  - OBJECTIVES: The objective of the study is to compare the efficacy of
      hypoglycaemic drugs for type 2 diabetes mellitus (T2DM) by network meta-analysis
      of randomized controlled trials (RCTs). METHODS: We compared 11 major oral
      hypoglycaemic drugs under five categories evaluated by RCTs as drug monotherapy
      for the patients with T2DM, measuring glycosylated haemoglobin (%) or fasting
      plasma glucose (mmol L-1) as outcomes. RCT quality was assessed with the Cochrane
      risk of bias tool. Network meta-analysis estimated the mean differences and 95%
      credible intervals. Subgroup and sensitivity analyses were performed to determine
      the results robustness. The Grading of Recommendation, Assessment, Development,
      and Evaluation evidence strength was assessed. RESULTS: Seventy-five RCTs
      including 33,830 patients were identified. Their study quality was high.
      Regarding glycosylated haemoglobin, top three anti-diabetics were repaglinide
      (mean differences -1.39 [95% credible intervals -1.75 to -1.03]), gliclazide (
      1.37 [-2.04 to -0.71]) and metformin (-1.13 [-1.37 to -0.90]), against placebo.
      Regarding fasting plasma glucose, top three anti-diabetics were repaglinide (
      2.01 [-2.75 to -0.97]), metformin (-1.72 [-2.16 to -1.27]) and glipizide (-1.57 [
      2.44 to -0.64]), against placebo. There was no difference between metformin and
      repaglinide. Subgroup and sensitivity analyses found the results to be robust.
      The evidence strength was moderate to high. CONCLUSION: This meta-analysis showed
      that repaglinide and metformin would be the most efficacious oral drugs for first
      line monotherapy of T2DM.

PMID- 30230173
TI  - Pancreatic islet of Langerhans' cytoarchitecture and ultrastructure in normal
      glucose tolerance and in type 2 diabetes mellitus.
AB  - While a number of structural and cellular abnormalities occur in the islet of
      Langerhans in diabetes, and in particular in type 2 diabetes, the focus has been
      mostly on the insulin producing beta-cells and only more recently on glucagon
      producing alpha- and delta-cells. There is ample evidence that in type 2 diabetes
      mellitus (T2DM), in addition to a progressive decline in beta-cell function and
      associated insulin resistance in a number of insulin-sensitive tissues,
      alterations in glucagon secretion are also present and may play an important role
      in the pathogenesis of hyperglycemia both in the fasting and in the postprandial
      state. Recently, a number of studies have showed that there are also functional
      and structural alterations in glucagon-producing alpha-cells and somatostatin
      producing delta-cells. Thus, it is becoming increasingly clear that multiple
      cellular alterations of multiple cell types occur, which adds even more
      complexity to our understanding of the pathophysiology of this common and severe
      disease. We believe that persistent efforts to increase the understanding of the
      pathophysiology of hormone secretion in the islets of Langerhans will also
      improve our capability to better prevent and treat diabetes mellitus.

PMID- 30230176
TI  - Single molecule approaches for studying gene regulation in metabolic tissues.
AB  - Gene expression in metabolic tissues can be regulated at multiple levels, ranging
      from the control of promoter accessibilities, transcription rates, mRNA
      degradation rates and mRNA localization. Modulating these processes can
      differentially affect important performance criteria of cells. These include
      precision, cellular economy, rapid response and maintenance of DNA integrity. In
      this review we will describe how distinct strategies of gene regulation impact
      the trade-offs between the cells' performance criteria. We will highlight tools
      based on single molecule visualization of transcripts that can be used to measure
      promoter states, transcription rates and mRNA degradation rates in intact
      tissues. These approaches revealed surprising recurrent patterns in mammalian
      tissues, that include transcriptional bursting, nuclear retention of mRNA, and
      coordination of mRNA lifetimes to facilitate rapid adaptation to changing
      metabolic inputs. The ability to characterize gene expression at the single
      molecule level can uncover the design principles of gene regulation in metabolic
      tissues such as the liver and the pancreas.

PMID- 30230177
TI  - Time zones of pancreatic islet metabolism.
AB  - Most living beings possess an intrinsic system of circadian oscillators, allowing
      anticipation of the Earth's rotation around its own axis. The mammalian circadian
      timing system orchestrates nearly all aspects of physiology and behaviour.
      Together with systemic signals originating from the central clock that resides in
      the hypothalamic suprachiasmatic nucleus, peripheral oscillators orchestrate
      tissue-specific fluctuations in gene transcription and translation, and
      posttranslational modifications, driving overt rhythms in physiology and
      behaviour. There is accumulating evidence of a reciprocal connection between the
      circadian oscillator and most aspects of physiology and metabolism, in particular
      as the circadian system plays a critical role in orchestrating body glucose
      homeostasis. Recent reports imply that circadian clocks operative in the
      endocrine pancreas regulate insulin secretion, and that islet clock perturbation
      in rodents leads to the development of overt type 2 diabetes. While whole islet
      clocks have been extensively studied during the last years, the heterogeneity of
      islet cell oscillators and the interplay between alpha- and beta-cellular clocks
      for orchestrating glucagon and insulin secretion have only recently gained
      attention. Here, we review recent findings on the molecular makeup of the
      circadian clocks operative in pancreatic islet cells in rodents and in humans,
      and focus on the physiologically relevant synchronizers that are resetting these
      time-keepers. Moreover, the implication of islet clock functional outputs in the
      temporal coordination of metabolism in health and disease will be highlighted.

PMID- 30230174
TI  - When one becomes many-Alternative splicing in beta-cell function and failure.
AB  - Pancreatic beta-cell dysfunction and death are determinant events in type 1
      diabetes (T1D), but the molecular mechanisms behind beta-cell fate remain poorly
      understood. Alternative splicing is a post-translational mechanism by which a
      single gene generates different mRNA and protein isoforms, expanding the
      transcriptome complexity and enhancing protein diversity. Neuron-specific and
      certain serine/arginine-rich RNA binding proteins (RBP) are enriched in beta
      cells, playing crucial roles in the regulation of insulin secretion and beta-cell
      survival. Moreover, alternative exon networks, regulated by inflammation or
      diabetes susceptibility genes, control key pathways and processes for the correct
      function and survival of beta-cells. The challenge ahead of us is to understand
      the precise role of alternative splicing regulators and splice variants on beta
      cell function, dysfunction and death and develop tools to modulate it.

PMID- 30230178
TI  - Islet stress, degradation and autoimmunity.
AB  - beta-cell destruction in type 1 diabetes (T1D) results from the effect of
      inflammation and autoimmunity. In response to inflammatory signals, islet cells
      engage adaptive mechanisms to restore and maintain cellular homeostasis. Among
      these mechanisms, the unfolded protein response (UPR) leads to a reduction of the
      general protein translation rate, increased production of endoplasmic reticulum
      chaperones and the initiation of degradation by activation of the ER associated
      degradation pathway (ERAD) in which newly synthetized proteins are
      ubiquitinylated and processed through the proteasome. This adaptive phase is also
      believed to play a critical role in the development of autoimmunity by the
      generation of neoantigens. While we have previously investigated the effect of
      stress on transcription, translation and post-translational events as possible
      source for neoantigens, the participation of the degradation machinery, yet
      crucial in the generation of antigenic peptides, remains to be investigated in
      the context of T1D pathology. In this review, we will describe the relation
      between the unfolded protein response and the Ubiquitin Proteasome System (UPS)
      and address the role of the cellular degradation machinery in the generation of
      antigens. Learning from tumour immunology, we propose how these processes may
      unmask beta-cells by triggering the generation of aberrant peptides recognized by
      the immune cells.

PMID- 30230175
TI  - A thing of beauty: Structure and function of insulin's "aromatic triplet".
AB  - The classical crystal structure of insulin was determined in 1969 by D.C. Hodgkin
      et al. following a 35-year program of research. This structure depicted a hexamer
      remarkable for its self-assembly as a zinc-coordinated trimer of dimer. Prominent
      at the dimer interface was an "aromatic triplet" of conserved residues at
      consecutive positions in the B chain: PheB24 , PheB25 and TyrB26 . The elegance
      of this interface inspired the Oxford team to poetry: "A thing of beauty is a joy
      forever" (John Keats as quoted by Blundell, T.L., et al. Advances in Protein
      Chemistry 26:279-286 [1972]). Here, we revisit this aromatic triplet in light of
      recent advances in the structural biology of insulin bound as a monomer to
      fragments of the insulin receptor. Such co-crystal structures have defined how
      these side chains pack at the primary hormone-binding surface of the receptor
      ectodomain. On receptor binding, the B-chain beta-strand (residues B24-B28)
      containing the aromatic triplet detaches from the alpha-helical core of the
      hormone. Whereas TyrB26 lies at the periphery of the receptor interface and may
      functionally be replaced by a diverse set of substitutions, PheB24 and PheB25
      engage invariant elements of receptor domains L1 and alphaCT. These critical
      contacts were anticipated by the discovery of diabetes-associated mutations at
      these positions by Donald Steiner et al. at the University of Chicago.
      Conservation of PheB24 , PheB25 and TyrB26 among vertebrate insulins reflects the
      striking confluence of structure-based evolutionary constraints: foldability,
      protective self-assembly and hormonal activity.

PMID- 30230179
TI  - Islet prohormone processing in health and disease.
AB  - Biosynthesis of peptide hormones by pancreatic islet endocrine cells is a tightly
      orchestrated process that is critical for metabolic homeostasis. Like
      neuroendocrine peptides, insulin and other islet hormones are first synthesized
      as larger precursor molecules that are processed to their mature secreted
      products through a series of proteolytic cleavages, mediated by the prohormone
      convertases Pc1/3 and Pc2, and carboxypeptidase E. Additional posttranslational
      modifications including C-terminal amidation of the beta-cell peptide islet
      amyloid polypeptide (IAPP) by peptidyl-glycine alpha-amidating monooxygenase
      (Pam) may also occur. Genome-wide association studies (GWAS) have showed genetic
      linkage of these processing enzymes to obesity, beta-cell dysfunction, and type 2
      diabetes (T2D), pointing to their important roles in metabolism and blood glucose
      regulation. In both type 1 diabetes (T1D) and T2D, and in the face of metabolic
      or inflammatory stresses, islet prohormone processing may become impaired; indeed
      elevated proinsulin:insulin (PI:I) ratios are a hallmark of the beta-cell
      dysfunction in T2D. Recent studies suggest that genetic or acquired defects in
      proIAPP processing may lead to the production and secretion of incompletely
      processed forms of proIAPP that could contribute to T2D pathogenesis, and
      additionally that impaired processing of both PI and proIAPP may be
      characteristic of beta-cell dysfunction in T1D. In islet alpha-cells, the
      prohormone proglucagon is normally processed to bioactive glucagon by Pc2 but may
      express Pc1/3 under certain conditions leading to production of GLP-1(7-36NH2 ).
      A better understanding of how beta-cell processing of PI and proIAPP, as well as
      alpha-cell processing of proglucagon, are impacted by genetic susceptibility and
      in the face of diabetogenic stresses, may lead to new therapeutic approaches for
      improving islet function in diabetes.

PMID- 30230181
TI  - MicroRNAs in islet hormone secretion.
AB  - Pancreatic islet hormone secretion is central in the maintenance of blood glucose
      homeostasis. During development of hyperglycaemia, the beta-cell is under
      pressure to release more insulin to compensate for increased insulin resistance.
      Failure of the beta-cells to secrete enough insulin results in type 2 diabetes
      (T2D). MicroRNAs (miRNAs) are short non-coding RNA molecules suitable for rapid
      regulation of the changes in target gene expression needed in beta-cell
      adaptations. Moreover, miRNAs are involved in the maintenance of alpha-cell and
      beta-cell phenotypic identities via cell-specific, or cell-enriched expression.
      Although many of the abundant miRNAs are highly expressed in both cell types,
      recent research has focused on the role of miRNAs in beta-cells. It has been
      shown that highly abundant miRNAs, such as miR-375, are involved in several
      cellular functions indispensable in maintaining beta-cell phenotypic identity,
      almost acting as "housekeeping genes" in the context of hormone secretion.
      Despite the abundance and importance of miR-375, it has not been shown to be
      differentially expressed in T2D islets. On the contrary, the less abundant miRNAs
      such as miR-212/miR-132, miR-335, miR-130a/b and miR-152 are deregulated in T2D
      islets, wherein the latter three miRNAs were shown to play key roles in
      regulating beta-cell metabolism. In this review, we focus on beta-cell function
      and describe miRNAs involved in insulin biosynthesis and processing, glucose
      uptake and metabolism, electrical activity and Ca2+ -influx and exocytosis of the
      insulin granules. We present current status on miRNA regulation in alpha-cells,
      and finally we discuss the involvement of miRNAs in beta-cell dysfunction
      underlying T2D pathogenesis.

PMID- 30230180
TI  - tRNA modifications and islet function.
AB  - Efficient and accurate protein translation is essential to producing insulin in
      pancreatic beta-cells. Transfer RNA (tRNA) is known as the key component of the
      protein translational machinery. Interestingly, tRNA contains a wide variety of
      chemical modifications, which are posttranscriptionally catalysed by tRNA
      modifying enzymes. Recent advances in genome-sequencing technology have unveiled
      a number of genetic variations that are associated with the development of type 2
      diabetes (T2D). Some of these mutations are located in the genes of tRNA
      modifying enzymes. Using cellular and animal models, it has been showed that
      dysregulation of tRNA modification impairs protein translation in pancreatic beta
      cells and leads to aberrant insulin production. In this review, we discuss the
      recent findings in the molecular functions of tRNA modifications and their
      involvement in the development of T2D.

PMID- 30230182
TI  - Effects of proinsulin misfolding on beta-cell dynamics, differentiation and
      function in diabetes.
AB  - ER stress due to proinsulin misfolding has an important role in the
      pathophysiology of rare forms of permanent neonatal diabetes (PNDM) and probably
      also of common type 1 (T1D) and type 2 diabetes (T2D). Accumulation of misfolded
      proinsulin in the ER stimulates the unfolded protein response (UPR) that may
      eventually lead to apoptosis through a process called the terminal UPR. However,
      the beta-cell ER has an incredible ability to cope with accumulation of misfolded
      proteins; therefore, it is not clear whether in common forms of diabetes the
      accumulation of misfolded proinsulin exceeds the point of no return in which
      terminal UPR is activated. Many studies showed that the UPR is altered in both
      T1D and T2D; however, the observed changes in the expression of different UPR
      markers are inconsistent and it is not clear whether they reflect an adaptive
      response to stress or indeed mediate the beta-cell dysfunction of diabetes.
      Herein, we critically review the literature on the effects of proinsulin
      misfolding and ER stress on beta-cell dysfunction and loss in diabetes with
      emphasis on beta-cell dynamics, and discuss the gaps in understanding the role of
      proinsulin misfolding in the pathophysiology of diabetes.

PMID- 30230184
TI  - Role of ghrelin in pancreatic development and function.
AB  - Ghrelin is a gastric peptide with anabolic functions. It acutely stimulates
      growth hormone (GH) secretion from the anterior pituitary glands and modulates
      hypothalamic circuits that control food intake and energy expenditure. Besides
      its central activity, ghrelin is also involved in the regulation of pancreatic
      development and physiology. Particularly, several studies highlighted the ability
      of ghrelin to sustain beta-cell viability and proliferation. Furthermore, ghrelin
      seems to exert inhibitory effects on pancreatic acinar and endocrine secretory
      functions. Due to its pleiotropic activity on energy metabolism, ghrelin has
      become a topic of great interest for experimental research focused on type II
      diabetes and obesity. The aim of this review is to illustrate the complex and not
      fully understood interplay between ghrelin, pancreas and glucose homeostasis.

PMID- 30230185
TI  - Biosynthesis, structure, and folding of the insulin precursor protein.
AB  - Insulin synthesis in pancreatic beta-cells is initiated as preproinsulin.
      Prevailing glucose concentrations, which oscillate pre- and postprandially, exert
      major dynamic variation in preproinsulin biosynthesis. Accompanying upregulated
      translation of the insulin precursor includes elements of the endoplasmic
      reticulum (ER) translocation apparatus linked to successful orientation of the
      signal peptide, translocation and signal peptide cleavage of preproinsulin-all of
      which are necessary to initiate the pathway of proper proinsulin folding.
      Evolutionary pressures on the primary structure of proinsulin itself have
      preserved the efficiency of folding ("foldability"), and remarkably, these
      evolutionary pressures are distinct from those protecting the ultimate biological
      activity of insulin. Proinsulin foldability is manifest in the ER, in which the
      local environment is designed to assist in the overall load of proinsulin folding
      and to favour its disulphide bond formation (while limiting misfolding), all of
      which is closely tuned to ER stress response pathways that have complex
      (beneficial, as well as potentially damaging) effects on pancreatic beta-cells.
      Proinsulin misfolding may occur as a consequence of exuberant proinsulin
      biosynthetic load in the ER, proinsulin coding sequence mutations, or genetic
      predispositions that lead to an altered ER folding environment. Proinsulin
      misfolding is a phenotype that is very much linked to deficient insulin
      production and diabetes, as is seen in a variety of contexts: rodent models
      bearing proinsulin-misfolding mutants, human patients with Mutant INS-gene
      induced Diabetes of Youth (MIDY), animal models and human patients bearing
      mutations in critical ER resident proteins, and, quite possibly, in more common
      variety type 2 diabetes.

PMID- 30230186
TI  - Lysosomes in nutrient signalling: A focus on pancreatic beta-cells.
AB  - Regulated insulin secretion from pancreatic beta-cells is a major process
      maintaining glucose homeostasis in mammals. Enhancing insulin release in response
      to chronic nutrient overload and obesity-related insulin resistance (pre
      diabetes) requires several adaptive cellular mechanisms maintaining beta-cell
      health under such stresses. Once these mechanisms are overwhelmed, beta-cell
      failure occurs leading to full-blown Type 2 Diabetes (T2D). Nutrient-dependent
      macroautophagy represents one such adaptive mechanism in beta-cells. While
      macroautophagy levels are high and protective in beta-cells in pre-diabetes, they
      decrease at later stages contributing to beta-cell failure. However, mechanisms
      compromising macroautophagy in beta-cells remain poorly understood. In this
      review, we discuss how recently discovered signalling cascades that emanate from
      the limiting membrane of lysosomes contribute to changes in macroautophagy flux
      in physiology and disease. In particular, these mechanisms are put into context
      with beta-cell function highlighting most recently described links between
      nutrient-dependent lysosomal signalling pathways and insulin secretion.
      Understanding these mechanisms in response to metabolic stress might pave the way
      for development of more tailored treatment strategies aimed at preserving beta
      cell health.

PMID- 30230183
TI  - Regulation of islet glucagon secretion: Beyond calcium.
AB  - The islet of Langerhans plays a key role in glucose homeostasis through regulated
      secretion of the hormones insulin and glucagon. Islet research has focused on the
      insulin-secreting beta-cells, even though aberrant glucagon secretion from alpha
      cells also contributes to the aetiology of diabetes. Despite its importance, the
      mechanisms controlling glucagon secretion remain controversial. Proper alpha-cell
      function requires the islet milieu, where beta- and delta-cells drive and
      constrain alpha-cell dynamics. The response of glucagon to glucose is similar
      between isolated islets and that measured in vivo, so it appears that the glucose
      dependence requires only islet-intrinsic factors and not input from blood flow or
      the nervous system. Elevated intracellular free Ca2+ is needed for alpha-cell
      exocytosis, but interpreting Ca2+ data is tricky since it is heterogeneous among
      alpha-cells at all physiological glucose levels. Total Ca2+ activity in alpha
      cells increases slightly with glucose, so Ca2+ may serve a permissive, rather
      than regulatory, role in glucagon secretion. On the other hand, cAMP is a more
      promising candidate for controlling glucagon secretion and is itself driven by
      paracrine signalling from beta- and delta-cells. Another pathway, juxtacrine
      signalling through the alpha-cell EphA receptors, stimulated by beta-cell ephrin
      ligands, leads to a tonic inhibition of glucagon secretion. We discuss potential
      combinations of Ca2+ , cAMP, paracrine and juxtacrine factors in the regulation
      of glucagon secretion, focusing on recent data in the literature that might unify
      the field towards a quantitative understanding of alpha-cell function.

PMID- 30230187
TI  - Variation in abundance of predicted resistance genes in the Brassica oleracea
      pangenome.
AB  - Brassica oleracea is an important agricultural species encompassing many
      vegetable crops including cabbage, cauliflower, broccoli and kale; however, it
      can be susceptible to a variety of fungal diseases such as clubroot, blackleg,
      leaf spot and downy mildew. Resistance to these diseases is meditated by specific
      disease resistance genes analogs (RGAs) which are differently distributed across
      B. oleracea lines. The sequenced reference cultivar does not contain all B.
      oleracea genes due to gene presence/absence variation between individuals, which
      makes it necessary to search for RGA candidates in the B. oleracea pangenome.
      Here we present a comparative analysis of RGA candidates in the pangenome of B.
      oleracea. We show that the presence of RGA candidates differs between lines and
      suggests that in B. oleracea, SNPs and presence/absence variation drive RGA
      diversity using separate mechanisms. We identified 59 RGA candidates linked to
      Sclerotinia, clubroot, and Fusarium wilt resistance QTL, and these findings have
      implications for crop breeding in B. oleracea, which may also be applicable in
      other crops species.

PMID- 30230188
TI  - Re: Patient-initiated follow up affects fear of recurrence and healthcare use: a
      randomised trial in early-stage endometrial cancer.

PMID- 30230189
TI  - Transcriptomic analysis of interactions between Hyphantria cunea larvae and
      nucleopolyhedrovirus.
AB  - BACKGROUND: Hyphantria cunea is a destructive forest pest. To utilise H. cunea
      nucleopolyhedrovirus (HcNPV) for biological control, understanding insect-virus
      interactions is essential. RESULTS: Four cDNA libraries were constructed from H.
      cunea larvae (two HcNPV-infected and two uninfected groups) and 76 004 expressed
      genes were obtained by next-generation sequencing. Compared with controls, 272
      differentially expressed genes (DEGs) were identified in infected groups,
      including 162 up-regulated and 110 down-regulated genes. Transcription levels of
      20 random DEGs were consistent with the Solexa expression profiles obtained by
      quantitative real-time PCR. DEGs associated with innate immunity were grouped
      into several categories, including pattern recognition proteins, heat-shock
      proteins, UDP-glycosyltransferases, cytochrome P450s, antimicrobial peptides and
      hormonal signalling proteins. Interestingly, up-regulated host genes included
      farnesoic acid O-methyltransferase, two juvenile hormone (JH) binding proteins,
      and a circadian clock-controlled protein related to JH regulation. Pathway
      enrichment analysis indicates that mitogen-activated protein kinase (MAPK)
      signalling pathways, key candidate genes and important biological pathways may be
      associated with molecular modification in H. cunea larvae in response to virus
      stress. CONCLUSION: These findings provide insight for future research on the
      molecular mechanisms of HcNPV invasion and anti-HcNPV mechanisms in H. cunea. A
      better understanding of gene regulation following HcNPV invasion could help to
      develop the virus as a bio-insecticide. (c) 2018 Society of Chemical Industry.

PMID- 30230191
TI  - Expansion of the Liver Donor Supply Through Greater Use of Split Liver
      Transplantation: Identifying Optimal Recipients.
AB  - The increased use of split liver transplantation (SLT) represents one strategy to
      increase the supply of organs. Although outcomes after SLT and whole liver
      transplantation (WLT) are similar on average among pediatric recipients, we
      hypothesized that the relationship between graft type and outcomes may vary
      depending on patient, donor, and surgical characteristics. We evaluated graft
      survival among pediatric (<18 years), deceased-donor, liver-only transplant
      recipients from March, 2002, until December, 2015, using data from the the
      Scientific Registry of Transplant Recipients. Graft survival was assessed in a
      Cox proportional hazards model, with and without effect modification between
      graft type and donor, recipient, and surgical characteristics, to identify
      conditions where the risk of graft loss for SLT and WLT were similar. In a
      traditional multivariable model, characteristics associated with graft loss
      included donor age >50 years, recipient weight <10 kg, acute hepatic necrosis,
      autoimmune diseases, tumor, public insurance, and cold ischemia time (CIT) >8
      hours. In an analysis that explored whether these characteristics modified the
      relationship between graft type and graft loss, many characteristics associated
      with loss actually had similar outcomes irrespective of graft type including
      weight <10 kg, acute hepatic necrosis, autoimmune diseases, and tumor. In
      contrast, several subgroups had worse outcomes when SLT was used, including
      recipient weight 10-35 kg, non-BA cholestasis, and metabolic disease. Allocation
      score, share type, or CIT did not modify risk of graft type and graft failure.
      Although one might anticipate that individuals with higher rates of graft loss
      would be worse candidates for SLT, data suggest that these patients actually have
      similar rates of graft loss. These findings can guide surgical decision-making
      and may support policy changes that promote the increased use of SLT for specific
      pediatric recipients. This article is protected by copyright. All rights
      reserved.

PMID- 30230190
TI  - Associations between maternal physical activity in early and late pregnancy and
      offspring birth size: remote federated individual level meta-analysis from eight
      cohort studies.
AB  - OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in
      pregnancy on birth size is inconsistent. We aimed to examine the association
      between LTPA during early and late pregnancy and newborn anthropometric outcomes.
      DESIGN: Individual level meta-analysis, which reduces heterogeneity across
      studies. SETTING: A consortium of eight population-based studies (seven European
      and one US) comprising 72 694 participants. METHODS: Generalised linear models
      with consistent inclusion of confounders (gestational age, sex, parity, maternal
      age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test
      associations between self-reported LTPA at either early (8-18 weeks gestation) or
      late pregnancy (30+ weeks) and the outcomes. Results were pooled using random
      effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational
      age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal
      index at birth. RESULTS: Late, but not early, gestation maternal moderate to
      vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure
      were modestly inversely associated with BW, LGA, macrosomia, and ponderal index,
      without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for
      LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98),
      respectively. Associations were only modestly reduced after additional
      adjustments for maternal BMI and gestational diabetes. No measure of LTPA was
      associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not
      early, pregnancy is consistently associated with modestly lower risk of LGA and
      macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta
      analysis, late pregnancy moderate to vigorous physical activity modestly reduced
      birth size outcomes.

PMID- 30230192
TI  - Whole-exome sequencing identifies novel pathogenic variants across the ATP7B gene
      and some modifiers of Wilson's disease phenotype.
AB  - BACKGROUND & AIMS: Wilson's disease (WD) is an autosomal recessive disorder
      associated with disease-causing alterations across the ATP7B gene, with highly
      variable symptoms and age of onset. We aimed to assess whether the clinical
      variability of WD relates to modifier genes. METHODS: A total of 248 WD patients
      were included, of whom 148 were diagnosed after age of 17. Human exome libraries
      were constructed using AmpliSeq technology and sequenced using the IonProton
      platform. RESULTS: ATP7B p.His1069Gln mutation was present in 215 patients, with
      112 homozygotes and 103 heterozygotes. Three other mutations: p.Gln1351Ter,
      p.Trp779Ter and c.3402delC were identified in >10 patients. Among patients, 117
      had a homozygous mutation, 101 were compound heterozygotes, 27 had one
      heterozygous mutation, and 3 other patients had no identifiable pathogenic
      variant of ATP7B. Sixteen mutations were novel, found as part of a compound
      mutation or as a sole, homozygous mutation. For disease phenotype prediction, age
      at diagnosis was a deciding factor, while frameshift allelic variants of ATP7B
      and being male increased the odds of developing a neurological phenotype. Rare
      allelic variants in ESD and INO80 increased and decreased chances for the
      neurological phenotype, respectively, while rare variants in APOE and MBD6
      decreased the chances of WD early manifestation. Compound mutations contributed
      to earlier age of onset. CONCLUSIONS: In a Polish population, genetic screening
      for WD may help genotype for four variants (p.His1069Gln, p.Gln1351Ter,
      p.Trp779Ter and c.3402delC), with direct sequencing of all ATP7B amplicons as a
      second diagnostic step. We also identified some allelic variants that may modify
      a WD phenotype.

PMID- 30230193
TI  - The Effect of Maternal Age on Obstetric Interventions in a Low-Risk Population.
AB  - INTRODUCTION: Obstetric interventions appear to increase with advancing maternal
      age, but limited supporting evidence exists, particularly for young women and
      specifically for prelabor and intrapartum cesarean birth. The aim of this study
      was to explore the association between obstetric interventions and maternal age
      in a low-risk population. METHODS: The study was restricted to all low-risk,
      nulliparous women with singleton, vertex, term births who gave birth in Iceland
      from 1997 to 2015, identified in the Icelandic Medical Birth Registry. Logistic
      regression models were used to calculate adjusted odds ratios (aORs) and 95% CIs
      for the risks of labor induction, instrumental birth, and cesarean birth
      (prelabor and intrapartum), according to maternal age group. All models were
      adjusted for gestational age, year of birth, and demographic factors, and the
      models for intrapartum cesarean birth were also adjusted for dystocia and fetal
      distress. RESULTS: For women aged more than 40 years, the aOR for induction of
      labor was 4.69 (95% CI, 3.2-6.8) compared with women aged between 25 and 29
      years. In women aged more than 40 years, the increased risks for prelabor
      cesarean birth and intrapartum cesarean birth were 7.4 (95% CI, 3.0-18.0) and 3.6
      (95% CI, 2.1-6.0), respectively. The risk of instrumental birth was slightly
      increased for women aged between 35 and 39 years (aOR, 1.6; 95% CI, 1.3-2.0),
      compared with women aged between 25 and 29 years, but not for women aged at least
      40 years (aOR, 1.1; 95% CI, 0.7-1.9). For women aged less than 20 years, the risk
      of induction of labor (aOR, 0.8; 95% CI, 0.7-0.9) and instrumental births (aOR,
      0.6; 95% CI, 0.5-0.7) was reduced compared with women aged between 25 and 29
      years. DISCUSSION: The risk of interventions generally increased with increasing
      maternal age, but the risk of instrumental births was not increased for women
      aged over 40 years. Also, young women were at a decreased risk of induction of
      labor and instrumental births.

PMID- 30230194
TI  - Hepatocellular carcinoma in Australia 1982-2014: Increasing incidence and
      improving survival.
AB  - BACKGROUND & AIMS: There is a paucity of accurate and current data on
      hepatocellular carcinoma (HCC) trends in incidence and survival in developed
      countries. We performed an Australia-wide assessment of HCC epidemiology across a
      33-year time span aiming to accurately describe changes in incidence and
      survival. METHODS: Cases of HCC from 1982 to 2014 were identified via the
      Australian Cancer Database (ACD). Trends in incidence rates were explored using
      piecewise linear regression. Survival was compared by Kaplan-Meier survival
      curves and 1-, 3- and 5-year survival probabilities by year of diagnosis.
      RESULTS: Age-adjusted HCC incidence rate increased from 1.38 per 100 000 (95% CI:
      1.34-1.43) in 1982 to 4.96 per 100 000 (95% CI: 4.89-5.03, P < 0.001) in 2014
      with an average annual percentage increase of 4.46% (95% CI: 4.24%-4.69%). The
      highest incidence rate in 2014 was in those aged 75-79 (24.31 per 100 000; 95%
      CI: 19.50-29.12). Almost 80% of cases across the period were men who had
      significantly higher age-adjusted incidence rates in 2014 than women (8.55 per
      100 000 [95% CI: 8.42-8.68] vs 1.65 per 100 000 [95% CI: 1.60-1.70]; P < 0.001).
      A hepatitis C (HCV) birth cohort effect was identified and associated with rapid
      increases in HCC incidence when members of the cohort aged and entered into age
      groups 45-49, 50-54 and 55-59. Median survival increased from 2.10 months (95%
      CI: 1.57-2.62 months) in those diagnosed between 1982 and 1984 to 12.07 months
      (95% CI: 11.17-12.97 months) when diagnosed between 2010 and 2014 (P < 0.001).
      CONCLUSIONS: An Australia-wide analysis of HCC epidemiological trends across
      three decades shows significant and consistent increases in both incidence and
      survival. LAY SUMMARY: There has been a significant increase in hepatocellular
      cancer (HCC) reported in Australia over the last three decades without evidence
      of slowing. Across the same time period, a significant improvement in survival
      has been identified with the average life expectancy after diagnosis now one
      year. This research lays the foundation for important public health service
      delivery.

PMID- 30230195
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 39/2018.

PMID- 30230196
TI  - Development of High Performance Heterogeneous Catalysts for Selective Cleavage of
      C-O and C-C Bonds of Biomass-derived Oxygenates.
AB  - The environmental impact of CO2 emissions via the use of fossil resources as
      chemical feedstock and fuels has stimulated research to utilize renewable biomass
      feedstock. The biogenic compounds such as polyols are highly oxygenated and their
      valorization requires the new methods to control the oxygen to carbon ratio of
      the chemicals. The catalytic cleavage of C-O bonds and C-C bonds is promising
      methods, but the conventional catalyst systems encounter the difficulty to obtain
      the high yields of the desired products. This review describes our recent
      development of the high performance heterogeneous catalysts for the valorization
      of the biogenic chemicals such as glycerol, furfural, and levulinic acid via
      selective cleavage of C-O bonds and C-C bonds in the liquid-phase. Selective C-O
      bond cleavage by hydrogenolysis enables production of various diols useful as
      engineering plastics, antifreeze, and cosmetics in high yields. The success of
      the selective C-C bond scission of levulinic acid can be applied to a wide range
      of the biogenic oxygenates such as carboxylic acids, esters, lactones, and
      primary alcohols, in which the selective C-C bond scission at adjacent to the
      oxygen functional groups are achieved. Furthermore, valorization of glycerol by
      selective acetylation and acetalization, and of levulinic acid by hydrogenation
      is described. Our catalysts show excellent performance compared to the reported
      catalysts in the aforementioned valorization.

PMID- 30230197
TI  - Automated Bright Field Segmentation of Cells and Vacuoles Using Image Processing
      Technique.
AB  - Understanding the mechanisms and other variants of programmed cell death will
      help provide deeper insight into various disease processes. Although complex
      procedures are required to distinguish each type of cell death, the formation of
      vacuoles is one of the important features in some process of cell death under
      different conditions. Thus, monitoring and counting the number of vacuoles and
      the ratio of cells with vacuoles is a commonly used method to indicate and
      quantify the efficacy of the therapy. Several studies have shown that image
      processing can provide a quick, convenient and precise mean of performing cell
      detection. Hence, this study uses an image processing technique to detect and
      quantify vacuolated cells without the need for dyes. The system both counts the
      number of vacuolated cells and determines the ratio of cells with vacuoles. The
      performance of the proposed image processing system was evaluated using 38
      images. It has been shown that a strong correlation exists between the automated
      counts and the manual counts. Furthermore, the absolute percentage errors between
      automated counts and manual counts for cell detection and vacuolated cell
      detection using data pooled from all images are 3.61 and 3.33%, respectively. A
      user-friendly graphical user interface (GUI) is also developed and freely
      available for download, providing researchers in biomedicine with a more
      convenient instrument for vacuolization analysis.

PMID- 30230198
TI  - Unusual presentation of an intra-abdominal mass: a rare case of Castleman disease
      of the greater omentum.

PMID- 30230200
TI  - Embracing the Focus of the Discipline of Nursing: Critical Caring Pedagogy.
AB  - PURPOSE: To present a theoretical model that grounds teaching and learning in
      nursing in the focus, values, and ideals of nursing as a discipline. ORGANIZING
      CONSTRUCTS: The critical caring pedagogy model was formed by integrating Falk
      Rafael's theory of critical caring in public health nursing, Noddings' philosophy
      of caring education, and Chinn's theory of peace and power. METHODS: The model of
      critical caring pedagogy was developed by logical analysis of the three
      organizing constructs and the conceptual relationships between and among these
      constructs. The analysis was informed by the authors' experiences implementing
      the theoretical constructs in teaching and learning. CONCLUSIONS: When nurse
      educators ground teaching and learning practice in nursing's own theoretical and
      philosophic foundation, they teach nursing in powerful ways that show nursing
      values and ideals through action, revealing deeper meanings of the words that
      form texts, lectures, and objectives set forth in a curriculum outline. CLINICAL
      RELEVANCE: Nursing students who experience education that is grounded in
      nursing's own disciplinary focus acquire an appreciation of nursing's
      disciplinary knowledge grounded in experience, paving the way for grounding their
      eventual practice in nursing theoretical perspectives.

PMID- 30230199
TI  - Dimerization of Metallofullerenes to Obtain Materials with Enhanced Nonlinear
      Optical Properties.
AB  - In this work, we theoretically designed a new class of fullerene derivatives,
      metallofullerene heterodimers, through cross dimerization of metallofullerene
      monomers Li@C60 , Y@C82 and Y2 @C80 . The molecular structures, electronic
      structures, linear and nonlinear optical properties of the heterodimers were
      studied by using density functional theory calculations. We found that two
      fullerene cages are connected through a relatively weak carbon-carbon single
      bond. Inter-cage electron transfer takes place in the heterodimers because of the
      different electron accepting abilities of the metallofullerene moieties. The
      first hyperpolarizability of the metallofullerenes increases remarkably as a
      result of dimerization. Time-dependent density functional theory calculations
      reveal that the enhanced first hyperpolarizability of the dimer is associated
      with charge-transfer transitions. This study demonstrates that covalent
      dimerization is an efficient means to improve the nonlinear optical response of
      metallofullerenes.

PMID- 30230202
TI  - Discovery and screening of novel metagenome-derived GH107 enzymes targeting
      sulfated fucans from brown algae.
AB  - Sulfated fucans, often denoted as fucoidans, are highly variable cell wall
      polysaccharides of brown algae, which possess a wide range of bioactive
      properties with potential pharmaceutical applications. Due to their complex
      architecture, the structures of algal fucans have until now only been partly
      determined. Enzymes capable of hydrolyzing sulfated fucans may allow specific
      release of defined bioactive oligosaccharides and may serve as a tool for
      structural elucidation of algal walls. Currently, such enzymes include only a few
      hydrolases belonging to the glycoside hydrolase family 107 (GH107), and little is
      known about their mechanistics and the substrates they degrade. In this study, we
      report the identification and recombinant production of three novel GH107 family
      proteins derived from a marine metagenome. Activity screening against a large
      substrate collection showed that all three enzymes degraded sulfated fucans from
      brown algae in the order Fucales. This is in accordance with a hydrolytic
      activity against alpha-1,4-fucosidic linkages in sulfated fucans as reported for
      previous GH107 members. Also, the activity screening gave new indications about
      the structural differences in brown algal cell walls. Finally, sequence analyses
      allowed identification of the proposed catalytic residues of the GH107 family.
      The findings presented here form a new basis for understanding the GH107 family
      of enzymes and investigating the complex sulfated fucans from brown algae.
      DATABASE: The assembled metagenome and raw sequence data is available at EMBL-EBI
      (Study number: PRJEB28480). Sequences of the GH107 fucanases (Fp273, Fp277, and
      Fp279) have been deposited in GenBank under accessions MH755451-MH755453.

PMID- 30230203
TI  - Five-tier utility: A start on the path to better reporting, in response to Schold
      and Buccini.

PMID- 30230204
TI  - Long-term administration of human albumin improves survival in patients with
      cirrhosis and refractory ascites.
AB  - BACKGROUND & AIMS: In patients with cirrhosis, the clinical benefit of the
      treatment with human albumin for ascites is debated, and no data are available
      regarding refractory ascites. In this study, in patients with cirrhosis and
      refractory ascites, we assessed the effect of long-term albumin administration on
      emergent hospitalization and mortality. METHODS: Seventy patients with cirrhosis
      and refractory ascites, followed at the Unit of Internal Medicine and Hepatology,
      University and General Hospital of Padova, Italy, were included into the study.
      Forty-five patients were non-randomly assigned to receive long-term
      administration of human albumin at the doses of 20 g twice per week (n = 45), in
      addition to standard medical of care (SOC), and compared to those followed
      according to SOC. Patients were followed up to the end of the study, liver
      transplantation or death. RESULTS: The cumulative incidence of 24-month mortality
      was significantly lower in patients treated with albumin than in the group of
      patients treated with SOC (41.6% vs 65.5%; P = 0.032). The period free of
      emergent hospitalization was significantly longer in patients treated with long
      term administration of albumin (P = 0.008). Analysing separately the causes of
      inpatient admission, patients treated with albumin showed a reduction in the
      incidence of overt hepatic encephalopathy, ascites, spontaneous bacterial
      peritonitis (SBP) and non-SBP infections. In addition, a non-significant trend
      towards a reduced probability of hepatorenal syndrome was observed. CONCLUSION:
      In patients with cirrhosis and refractory ascites, long-term treatment with
      albumin improves survival and reduces the probability of emergent
      hospitalizations.

PMID- 30230205
TI  - The quest for the optimal treatment for in-stent restenosis.

PMID- 30230201
TI  - Climatically controlled reproduction drives interannual growth variability in a
      temperate tree species.
AB  - Climatically controlled allocation to reproduction is a key mechanism by which
      climate influences tree growth and may explain lagged correlations between
      climate and growth. We used continent-wide datasets of tree-ring chronologies and
      annual reproductive effort in Fagus sylvatica from 1901 to 2015 to characterise
      relationships between climate, reproduction and growth. Results highlight that
      variable allocation to reproduction is a key factor for growth in this species,
      and that high reproductive effort ('mast years') is associated with stem growth
      reduction. Additionally, high reproductive effort is associated with previous
      summer temperature, creating lagged climate effects on growth. Consequently,
      understanding growth variability in forest ecosystems requires the incorporation
      of reproduction, which can be highly variable. Our results suggest that future
      response of growth dynamics to climate change in this species will be strongly
      influenced by the response of reproduction.

PMID- 30230206
TI  - Surgical aortic valve replacement and transcatheter aortic valve implantation for
      severe aortic stenosis: Equipoise remains a tenable assumption.

PMID- 30230207
TI  - TAVR for low-risk patients: The final Frontier.

PMID- 30230208
TI  - The less complex the case is, the more complex is it to choose? The case of lower
      risk patients with aortic valve stenosis.

PMID- 30230209
TI  - The Quandary of Volume! How Much Is Enough?

PMID- 30230210
TI  - Radial hemostasis: Harder, better, faster, stronger?

PMID- 30230211
TI  - Adventures across the second dimension: Predicting left ventricular outflow tract
      obstruction following transcatheter mitral valve replacement.

PMID- 30230212
TI  - Transcoronary pacing threshold predicts myocardial scar: Novel first-step towards
      intraprocedural myocardial functional assessment.

PMID- 30230213
TI  - BVS restenosis: "Reappearance of the disappeared stent".

PMID- 30230214
TI  - Subclinical brain lesions after left atrial appendage occlusion: Does silence
      mean reassurance?

PMID- 30230215
TI  - Submassive pulmonary embolus: The challenge of thrombolytic decision-making in a
      heterogenous cohort.

PMID- 30230216
TI  - Same day discharge for peripheral arterial interventions: Who are we trying to
      satisfy?

PMID- 30230217
TI  - Onyx is the new black.

PMID- 30230218
TI  - C-peptide levels do not correlate with pancreas allograft failure: Multicenter
      retrospective analysis and discussion of the new OPT definition of pancreas
      allograft failure.
AB  - The OPTN Pancreas Transplantation Committee performed a multicenter retrospective
      study to determine if undetectable serum C-peptide levels correspond to center
      reported pancreas graft failures. C-peptide data from seven participating centers
      (n = 415 graft failures for transplants performed from 2002 to 2012) were
      analyzed pretransplant, at graft failure, and at return to insulin. One hundred
      forty-nine C-peptide values were submitted at pretransplant, 94 at return to
      insulin, and 233 at graft failure. There were 77 transplants with two available
      values (at pretransplant and at graft failure). For recipients in the study with
      pretransplant C-peptide <0.75 ng/mL who had a posttransplant C-peptide value
      available (n = 61), graft failure was declared at varying levels of C-peptide.
      High C-peptide values at graft failure were not explained by nonfasting testing
      or by individual center bias. Transplant centers declare pancreas graft failure
      at varying levels of C-peptide and do not consistently report C-peptide data.
      Until February 28, 2018, OPTN did not require reporting of posttransplant C
      peptide levels and it appears that C-peptide levels are not consistently used for
      evaluating graft function. C-peptide levels should not be used as the sole
      criterion for the definition of pancreas graft failure.

PMID- 30230219
TI  - Catalytic Enantioselective Flow Processes with Solid-Supported Chiral Catalysts.
AB  - Sustainability concerns are the wind in the sails for the development of novel,
      more selective catalytic processes. Hence, chiral catalysts play a crucial role
      in the green production of enantioenriched compounds. To further increase the
      green profile of this approach, the use of solid-supported catalytic species is
      appealing due to the reduced generation of waste, as well as the possibility of
      reusing the precious catalyst. Even more attractive is the implementation of flow
      processes based on these immobilized catalysts, a flexible strategy that allows
      to generate from milli- to multi-gram amounts of chiral product with a reduced
      footprint set-up. Herein, we will present the efforts devoted in our laboratory
      towards the immobilization of chiral catalysts and their use in single-pass,
      highly enantioselective, flow processes. Proline, diarylprolinols, other
      aminocatalysts, squaramides, thioureas, phosphoric acids and even chiral ligands
      and metal-based catalysts constitute our current toolkit of supported species for
      enantioselective catalysis.

PMID- 30230220
TI  - Structural and Functional Analysis of the Gut Microbiome for Toxicologists.
AB  - Characterizing the reciprocal interactions between toxicants, the gut microbiota,
      and the host, holds great promise for improving our mechanistic understanding of
      toxic endpoints. Advances in culture-independent sequencing analysis (e.g., 16S
      rRNA gene amplicon sequencing) combined with quantitative metabolite profiling
      (i.e., metabolomics) have provided new ways of studying the gut microbiome and
      have begun to illuminate how toxicants influence the structure and function of
      the gut microbiome. Developing a standardized protocol is important for
      establishing robust, reproducible, and importantly, comparative data. This
      protocol can be used as a foundation for examining the gut microbiome via
      sequencing-based analysis and metabolomics. Two main units follow: (1) analysis
      of the gut microbiome via sequencing-based approaches; and (2) functional
      analysis of the gut microbiome via metabolomics. (c) 2018 by John Wiley & Sons,
      Inc.

PMID- 30230221
TI  - Sitagliptin treatment increases GLP-1 without improving diabetes outcomes after
      total pancreatectomy with islet autotransplantation.

PMID- 30230222
TI  - Facile Photochemical Modification of Silk Protein-Based Biomaterials.
AB  - Silk protein-based materials show promise for application as biomaterials for
      tissue engineering. The simple and rapid photochemical modification of silk
      protein-based materials composed of either Bombyx mori silkworm silk or
      engineered spider silk proteins (eADF4(C16)) is reported. Radicals formed on the
      silk-based materials initiate the polymerization of monomers (acrylic acid,
      methacrylic acid, or allylamine) which functionalize the surface of the silk
      materials with poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), or
      poly(allylamine) (PAAm). To demonstrate potential applications of this type of
      modification, the polymer-modified silks are mineralized. The PAA- and PMAA
      functionalized silks are mineralized with calcium carbonate, whereas the PAAm
      functionalized silks are mineralized with silica, both of which provide a coating
      on the materials that may be useful for bone tissue engineering, which will be
      the subject of future investigations.

PMID- 30230223
TI  - Mechanisms and Inhibitors of Histone Arginine Methylation.
AB  - Histone methylation plays an important regulatory role in chromatin restructuring
      and RNA transcription. Arginine methylation that is enzymatically catalyzed by
      the family of protein arginine methyltransferases (PRMTs) can either activate or
      repress gene expression depending on cellular contexts. Given the strong
      correlation of PRMTs with pathophysiology, great interest is seen in
      understanding molecular mechanisms of PRMTs in diseases and in developing potent
      PRMT inhibitors. Herein, we reviewed key research advances in the study of
      biochemical mechanisms of PRMT catalysis and their relevance to cell biology. We
      highlighted how a random binary, ordered ternary kinetic model for PRMT1
      catalysis reconciles the literature reports and endorses a distributive mechanism
      that the enzyme active site utilizes for multiple turnovers of arginine
      methylation. We discussed the impacts of histone arginine methylation and its
      biochemical interplays with other key epigenetic marks. Challenges in developing
      small-molecule PRMT inhibitors were also discussed.

PMID- 30230224
TI  - Proteomics Analysis for Verification of Rheumatoid Arthritis Biomarker Candidates
      Using Multiple Reaction Monitoring.
AB  - PURPOSE: Rheumatoid arthritis (RA) is an autoimmune disease in which
      autoantibodies attack the synovial membrane, causing joint inflammation. Blood
      tests would offer a powerful, minimally invasive method for early diagnosis of
      RA. However, no reliable biomarkers for RA are presently available. The aim is to
      develop biomarkers for RA by multiple reaction monitoring (MRM)-based
      quantification of candidate biomarkers. EXPERIMENTAL DESIGN: Proteomics
      approaches are commonly used to identify and verify disease biomarkers. For
      discovery of biomarkers for RA, SWATH acquisition is performed and selected
      candidate biomarkers are validated by MRM. Target serum proteins are compared
      between patients with RA and healthy controls divided into three groups based on
      rheumatoid factor level. RESULTS: A total of 45 differentially expressed proteins
      are identified, as determined by SWATH acquisition. Of these, 13 proteins are
      selected as novel candidate biomarkers. A total of five proteins (transthyretin,
      gelsolin, angiotensinogen, lipopolysaccharide-binding protein, and protein S100
      A9) are shown to have the potential to distinguish patients with RA from healthy
      controls. CONCLUSIONS AND CLINICAL RELEVANCE: These five proteins may improve the
      efficiency of diagnosis of RA. MRM can be used to easily diagnose RA by detecting
      five proteins simultaneously in a single sample with high sensitivity.

PMID- 30230225
TI  - Revised antiemetics guidelines and the impact on nutritional status during
      induction chemotherapy in children with high-risk neuroblastoma.
AB  - BACKGROUND: High-risk neuroblastoma (HR NBL) treatment requires intensive
      induction chemotherapy. The profoundly emetogenic agents used can compromise
      nutritional status. Our institution introduced a new antiemetic guideline in 2010
      incorporating regular dexamethasone, in addition to ondansetron, for all highly
      emetogenic protocols. PROCEDURE: A retrospective comparative review of pediatric
      patients diagnosed with HR NBL who received rapid COJEC induction chemotherapy as
      per HR-SIOPEN NBL trial. Prophylactic antiemetics were prescribed regardless of
      chemotherapy emetogenicity in group A (2004-2010) but for defined time periods
      considering chemotherapy emetogenicity in group B (2010-2017). RESULTS: Sixty
      three children were eligible for inclusion (median age, 31 months; range, 1-88
      months). Group A had more episodes of emesis than group B (189 vs. 116, P <
      0.0001). There was a significant difference in weight-for-age Z score change
      between the groups by induction end (P = 0.0027). Four children (13%) in group A
      lost >10% body weight versus none in group B. Nutrition support (NS) was utilized
      by 29 children (94%) in group A and 22 children (69%) in group B. Group A had a
      median of 3 (range, 1-7) admissions for febrile neutropenia (FN) versus a median
      of 1.5 (range, 0-4) for group B (P = 0.003) during induction. CONCLUSION: The
      review of our guidelines led to reduced emesis frequency for group B. They also
      required less NS, followed expected growth trajectories more closely and had
      fewer FN admissions. We propose that this may have occurred due to better emesis
      control resulting in improved nutritional status and associated enhanced immune
      function.

PMID- 30230226
TI  - Enhancing Type I Photochemistry in Photodynamic Therapy Under Near Infrared Light
      by Using Antennae-Fullerene Complexes.
AB  - Photodynamic therapy (PDT) has been developed as salvage or palliative treatment
      for a wide range of tumors. The principle underlying this therapy is the
      generation of reactive oxygen species through two types of photochemical
      pathways. As compared with the type II pathway, the type I pathway offers a
      higher oxidizing ability for photosensitive residues such as tryptophan, lower
      oxygen dependency, and deeper tissue penetration ability. In this review, we
      focus on the enhancement of the type I pathway in the near infrared (NIR) optical
      therapeutic window of wavelength 700-1,100 nm by using antennae-fullerene
      complexes. When photo-induced electron transfer occurs from antennas to
      fullerene, the pathway switches from type II to type I. Enhancing the type I
      pathway leads to less oxygen dependency and stronger capacity for tryptophan
      oxidation. Then, antennae that transfer long-wavelength light (e.g., NIR light)
      energy to fullerene via photo-induced energy and/or electron transfer have the
      ability to affect deep-seated tumors. On the basis of theories on photo-induced
      energy/electron transfer in other fields such as solar cells, here, we summarize
      the mechanism by which the switch from the type II to type I pathway occurs in
      antenna-fullerene-based PDT.

PMID- 30230227
TI  - Synthesis and evaluation of 2-azetidinone and 1H-pyrrole-2,5-dione derivatives as
      cholesterol absorption inhibitors for reducing inflammation response and
      oxidative stress.
AB  - Excess lipid accumulation can initiate the development and progression of
      atherosclerotic lesions, thus eventually leading to cardiovascular disease. Lipid
      lowering medication therapy is one of the cornerstones of cardiovascular disease
      therapy. On the basis of the cholesterol absorption inhibitor ezetimibe, we
      successfully synthesized seven 2-azetidinone derivatives and eighteen 1H-pyrrole
      2,5-dione derivatives. Most of the new compounds significantly inhibited
      cholesterol uptake in vitro. In addition, one of the most active inhibitors,
      compound 14q, showed no cytotoxicity in L02 and HEK293T cell lines. Further
      evaluation indicated 14q considerably inhibited the amount of TNF-alpha, ROS,
      MDA, and LDH in vitro. Therefore, 14q might be a novel cholesterol absorption
      inhibitor.

PMID- 30230228
TI  - Role of Skin Layers on Mechanical Properties and Supercontraction of Spider
      Dragline Silk Fiber.
AB  - Spider dragline silk is a composite biopolymer that harbors extraordinary
      mechanical characteristics, and consists of a hierarchically arranged protein
      core surrounded by outer "skin" layers. However, the contribution of the
      successive fiber layers on material properties has not been well defined. Here,
      the influence of the different components on the physicochemical and mechanical
      properties of dragline is investigated. The crystal structure and the mechanical
      properties are not changed significantly after the removal of skin constituents,
      indicating that the core region of dragline silk fibers determines the structural
      and mechanical properties. Furthermore, the outer layers have little influence on
      supercontraction, suggesting they do not function as protection against the
      penetration of water molecules. On the other hand, the outer layers offer some
      protection against protease digestion. The present study provides insight into
      how the function and structure of silk fibers are modulated and facilitates the
      design of silk-inspired functional materials.

PMID- 30230229
TI  - Ex vivo perfusion induces a time- and perfusate-dependent molecular repair
      response in explanted porcine lungs.
AB  - Ex vivo lung perfusion (EVLP) shows promise in ameliorating pretransplant acute
      lung injury (ALI) and expanding the donor organ pool, but the mechanisms of ex
      vivo repair remain poorly understood. We aimed to assess the utility of gene
      expression for characterizing ALI during EVLP. One hundred sixty-nine porcine
      lung samples were collected in vivo (n = 25), after 0 (n = 11) and 12 (n = 11)
      hours of cold static preservation (CSP), and after 0 (n = 57), 6 (n = 8), and 12
      (n = 57) hours of EVLP, utilizing various ventilation and perfusate strategies.
      The expression of 53 previously described ALI-related genes was measured and
      correlated with function and histology. Twenty-eight genes were significantly
      upregulated and 6 genes downregulated after 12 hours of EVLP. Aggregate gene sets
      demonstrated differential expression with EVLP (P < .001) but not CSP.
      Upregulated 28-gene set expression peaked after 6 hours of EVLP, whereas
      downregulated 6-gene set expression continued to decline after 12 hours. Cellular
      perfusates demonstrated a greater reduction in downregulated 6-gene set
      expression vs acellular perfusate (P < .038). Gene set expression correlated with
      relevant functional and histologic parameters, including P/F ratio (P < .001) and
      interstitial inflammation (P < .005). Further studies with posttransplant results
      are warranted to evaluate the clinical significance of this novel molecular
      approach for assessing organ quality during EVLP.

PMID- 30230230
TI  - Impact of acutely behavioural disturbed patients in the emergency department: A
      prospective observational study.
AB  - OBJECTIVE: The present study describes patients with acute behavioural
      disturbance presenting to the ED, the impact they have on the department and any
      complications that occur. METHODS: We performed a prospective observational study
      of adult patients (>17 years old) requiring parenteral sedation for acute
      behavioural disturbance over a 13 month period. Demographic data, mode of
      arrival, indication, drug type and dosing used for sedation were collected.
      Departmental data were recorded including the staff type and numbers involved and
      the condition of the department. The main outcomes were complications from
      sedative medication and injury sustained to patients or staff. RESULTS: Over the
      study period 173 patients met inclusion criteria, the majority (n = 104, 60%)
      were men with a mean age of 38.5 years (standard deviation 14.4); 51% of patients
      had more than one indication for sedation (n = 89), the commonest being mental
      health related plus drug intoxication (n = 30, 33.7%). Intoxication was
      frequently from either alcohol (n = 62, 47%) or methamphetamine (n = 41, 31%).
      The median number of staff involved was 10 (interquartile range 8-12). Staff
      members received an injury in 12% (n = 20) of sedations, with only 1% (n = 2) of
      patients receiving any physical injury; 12% (n = 20) had a minor complication
      from the sedation medication. No patient had any major complication (apnoea,
      intubation, arrhythmias or cardiac arrest). CONCLUSION: Patients with acute
      behavioural disturbance often have a history of mental illnesses and are commonly
      intoxicated. These patients have impacts on healthcare resources and pose risks
      to staff safety, but significant complications to patients do not occur
      frequently.

PMID- 30230231
TI  - Alternative treatment options for pediatric hemophilia B patients with high
      responding inhibitors: A thrombin generation-guided study.
AB  - Little is known about the challenging treatment of pediatric patients with
      hemophilia B and inhibitors due to disease rarity. We describe three patients
      diagnosed in childhood and followed up to 9 years. All three had allergic
      reactions to Factor IX, but two were later safely treated for bleeding episodes
      with activated prothrombin complex concentrates (APCC = FEIBA). The third was
      given only recombinant activated Factor VIIa. Based on ex vivo thrombin
      generation analysis, a new alternative treatment of combined bypassing agents was
      administered for bleeding episodes and several minor surgical procedures with no
      treatment-associated adverse events or thrombosis.

PMID- 30230232
TI  - Hospital resource utilization and presence of advance directives at the end of
      life for adults with congenital heart disease.
AB  - OBJECTIVE: Overall health care resource utilization by adults with congenital
      heart disease has increased dramatically in the past two decades, yet little is
      known about utilization patterns at the end of life. The objective of this study
      is to better understand the patterns and influences on end-of-life care intensity
      for adults with congenital heart disease. METHODS: We identified a sample of
      adults with congenital heart disease (n = 65), cancer (n = 10 784), or heart
      failure (n = 3809) who died between January 2010 and December 2015, cared for in
      one multi-hospital health care system. We used multivariate analysis to evaluate
      markers of resource utilization, location of death, and documentation of advance
      care planning among patients with congenital heart disease versus those with
      cancer and those with heart failure. RESULTS: Approximately 40% of adults with
      congenital heart disease experienced inpatient and intensive care unit (ICU)
      hospitalizations in the last 30 days of life; 64% died in the hospital. Compared
      to patients with cancer, patients with adult congenital heart disease (ACHD) were
      more likely to have inpatient (adjusted risk ratio 1.57; 95% CI 1.12-2.18) and
      ICU admissions in the last 30 days of life (adjusted risk ratio 2.56; 95% CI 1.83
      3.61), more likely to die in the hospital (adjusted risk ratio 1.75; 95% CI 1.43
      2.13), and more likely to have documentation of advance care planning (adjusted
      risk ratio 1.46; 95% CI 1.09-1.96). Compared to patients with heart failure (HF),
      patients with ACHD were less likely to have an ICU admission in the last 30 days
      of life (adjusted risk ratio 0.73; 95% CI 0.54-0.99). CONCLUSIONS: Adults with
      congenital heart disease have significant hospital resource utilization near the
      end of life compared to patients with cancer, notable for more hospitalizations
      and a higher likelihood of death in the hospital. This population represents an
      important opportunity for the application of palliative and supportive care.

PMID- 30230233
TI  - Maternal behavioural determinants and livestock ownership are associated with
      animal source food consumption among young children during fasting in rural
      Ethiopia.
AB  - Religious fasting often involves abstention from animal source foods (ASFs).
      Although children are exempt, their diets are influenced by the widespread
      fasting practices. This study investigated the factors influencing ASF
      consumption among young children during the Lent fasting period in western
      Amhara, Ethiopia. We used baseline survey data from households with children 6-23
      months of age (n = 2,646). We conducted regression analysis to examine the
      maternal and household factors associated with ASF consumption and path analysis
      to examine the direct and indirect effects of maternal knowledge, beliefs, social
      norms, and livestock ownership on ASF consumption. Only 24% of children consumed
      any ASF in the previous day-18% dairy products, 5% eggs, and 2% flesh foods.
      Mothers with high knowledge, beliefs, and social norms about feeding children
      ASFs during fasting had higher odds (odds ratio: 1.3-1.4) of children who
      consumed them. Compared with households with no ASFs, those with ASFs available
      were 4.8 times more likely to have children who consumed them. Most of the
      association between knowledge, beliefs and social norms, and ASF consumption was
      explained by pathways operating through ASF availability (approximately 9, 12,
      and 8 pp higher availability, respectively), which in turn were associated with
      higher consumption. Cow ownership was directly and indirectly associated with ASF
      consumption, whereas having chickens was indirectly associated with consumption
      via the availability pathway. Our findings corroborate the importance of maternal
      behavioural determinants related to feeding ASFs to children during fasting on
      ASF consumption via household availability and the positive influence of
      livestock ownership.

PMID- 30230234
TI  - Cobalt Nanocrystals Encapsulated in Heteroatom-Rich Porous Carbons Derived from
      Conjugated Microporous Polymers for Efficient Electrocatalytic Hydrogen
      Evolution.
AB  - Cobalt nanocrystals encapsulated in N,O-dual-doped porous carbons as efficient
      and stable electrocatalysts for hydrogen evolution reaction (HER) are reported. A
      heteroatom-rich-conjugated microporous polymer is first chemically deposited on a
      carbon fiber cloth, and after addition of a cobalt salt, pyrolyzed to produce a
      heteroatom-doped C/Co nanocrystal composite. With this process, the use of
      additional binders for preparation of electrodes can be avoided. With a trace
      cobalt loading (0.46 wt%), the electrodes achieve a low Tafel slope of 46 mV dec
      1 and overpotential of only 69 mV at a current density of 10 mA cm-2 in 0.5 m H2
      SO4 . Experimental and computational studies reveal that the superior HER
      behavior is due to a decreased free energy of hydrogen adsorption, induced by i)
      electrons transferred from the cobalt nanocrystals to graphite layers and ii) N,O
      dual doping reduced the Fermi level of neighboring C atoms.

PMID- 30230237
TI  - Center effect on posttransplant survival among currently active United States
      pediatric heart transplant centers.

PMID- 30230236
TI  - Measuring animal exposure in Canada: Foodbook study, 2014-2015.
AB  - Animal companionship can have many physical and psychological benefits; however,
      animals can also be a source of zoonotic infection, including enteric illnesses;
      it has been estimated that in Canada, nearly 85,000 enteric illnesses due to
      eight pathogens occur each year related to animal contact. There is a lack of
      baseline data on animal-related exposures in Canada and around the world. This
      information is critical to inform quantitative and qualitative risk assessments
      to prioritize intervention efforts in public health and reduce the associated
      burden of enteric illness. To help address this issue and assist evaluation of
      the risks associated with animal contact, the Foodbook study, conducted in 2014
      2015, assessed exposure to animals, animal food and animal-related venues within
      the last 7 days among Canadians. Data were analysed by province and territory,
      age group and urban/rural residency. Overall, dogs and cats were the most
      commonly reported animal exposures (43.3% and 31.9%, respectively). The data
      suggest farm animal exposure occurs primarily at a farm/barn, and to a lesser
      extent at other animal-related venues (e.g., petting zoos or agricultural fairs).
      Approximately one in 25 respondents handled raw pet food within the last 7 days;
      the majority of which had also been exposed to a dog (86.4%). Children aged 0-9
      years reported relatively high exposure to four types of high-risk animals:
      rodents (5.6%), poultry (4.0%), reptiles (2.1%) and amphibians (1.8%); with the
      most vulnerable children aged <5 years also reporting exposure to many of these
      high-risk animals. These results highlight potential areas for targeted
      intervention that can focus on high-risk populations (e.g., young children)
      exhibiting potentially risky behaviour such as being exposed to certain high-risk
      animals, or handling pet food, treats and raw pet food diets. Additionally, these
      results support the need to better understand the burden of enteric illness
      associated with animals and their environments.

PMID- 30230235
TI  - Redox-Responsive Nanoparticle-Mediated Systemic RNAi for Effective Cancer
      Therapy.
AB  - Biodegradable polymeric nanoparticles (NPs) have demonstrated significant
      potential to improve the systemic delivery of RNA interference (RNAi)
      therapeutics, such as small interfering RNA (siRNA), for cancer therapy. However,
      the slow and inefficient siRNA release inside tumor cells generally observed for
      most biodegradable polymeric NPs may result in compromised gene silencing
      efficacy. Herein, a biodegradable and redox-responsive NP platform, composed of a
      solid poly(disulfide amide) (PDSA)/cationic lipid core and a lipid-poly(ethylene
      glycol) (lipid-PEG) shell for systemic siRNA delivery to tumor cells, is
      developed. This newly generated NP platform can efficiently encapsulate siRNA
      under extracellular environments and can respond to the highly concentrated
      glutathione (GSH) in the cytoplasm to induce fast intracellular siRNA release. By
      screening a library of PDSA polymers with different structures and chain lengths,
      the optimized NP platform shows the unique features of i) long blood circulation,
      ii) high tumor accumulation, iii) fast GSH-triggered intracellular siRNA release,
      and iv) exceptionally effective gene silencing. Together with the facile polymer
      synthesis technique and robust NP formulation enabling scale-up, this new redox
      responsive NP platform may become an effective tool for RNAi-based cancer
      therapy.

PMID- 30230238
TI  - Design of multi-drug combinations for poly-pharmacological effects using
      composition-activity relationship modeling and multi-objective optimization
      approach: Application in traditional Chinese medicine.
AB  - In recent years, multi-component therapies are increasingly utilized to treat
      complex diseases such as cancer, diabetes, and other chronic complex diseases.
      Here, we proposed the protocol for rational design of drug combination with poly
      pharmacological effects by integration of design of experiments (DOE),
      computational modeling, and multiple-objective optimization algorithm. Here, we
      introduce a common workflow for modeling quantitative relationship of chemical
      composition and multiple activities of drug combinations. As an example, anti
      oxidation, neuroprotective, and anti-platelet activities of three different
      salvia polyphenols were measured, which were mathematically represented by
      multivariant regression models to evaluate the effect of combination. In
      validation, the optimized combination which obtained by weighed-sum method showed
      good activities in all three models. Our results demonstrate that the multiple
      objective optimization strategy is suitable to optimize the ratio of the
      compounds so to induce the best therapeutic action.

PMID- 30230239
TI  - Synthesis, insecticidal evaluation and 3D-QSAR study of novel anthranilic diamide
      derivatives as potential ryanodine receptor modulators.
AB  - BACKGROUND: Anthranilic diamide insecticides control lepidopteran pests through
      selectively binding and activating insect ryanodine receptors. In order to search
      for potential insecticides targeting the ryanodine receptors, a series of
      anthranilic diamide analogs including trifluoromethyl, nitro, or chloro groups
      were designed and synthesized by the principle of bioisosterism and structural
      optimization. RESULTS: Insecticidal data indicated that some compounds displayed
      good activity against oriental armyworm (Mythimna separata) and diamondback moth
      (Plutella xylostella). In particular, the larvicidal activity of 6p against P.
      xylostella was 95% at 0.01 mg L-1 , equivalent to chlorantraniliprole (85%, 0.01
      mg L-1 ). The comparative molecular similarity index analysis model obtained
      indicated that hydrogen bond acceptor and electron-withdrawing groups in the R'3
      group are favourable for insecticidal activity against M. separata, which is
      consistent with the structure-activity relationships. Moreover, the calcium
      imaging experiment indicated, like chlorantraniliprole, that 6h and 6p are
      interacting with the ryanodine receptor. CONCLUSION: Introducing trifluoromethyl,
      nitro, or chloro groups to a specific position in the N-phenylpyrazole could
      improve or maintain the activity against M. separata and P. xylostella. 6h and 6p
      could be used as potential lead compounds for ryanodine receptor modulators. (c)
      2018 Society of Chemical Industry.

PMID- 30230240
TI  - Inhibition of glial glutamate transporter GLT1 in the nucleus of the solitary
      tract attenuates baroreflex control of sympathetic nerve activity and heart rate.
AB  - The astrocytic glutamate transporter (GLT1) plays an important role in the
      maintenance of extracellular glutamate concentration below neurotoxic levels in
      brain. However, the functional role of GLT1 within the nucleus of the solitary
      tract (NTS) in the regulation of cardiovascular function remains unclear. We
      examined the effect of inhibiting GLT1 in the subpostremal NTS on mean arterial
      pressure (MAP), renal sympathetic nerve activity (RSNA) and heart rate (HR) in
      anesthetized, artificially ventilated rats. It was found that dihydrokainate
      (DHK; inhibitor of GLT1, 5 mmol/L, 100 nL) injections into the NTS (n = 6)
      decreased MAP (50 +/- 10 mmHg, mean +/- SD), RSNA (89 +/- 14%) and HR (37 +/- 6
      bpm). Pretreatment with kynurenate (KYN; glutamate receptor antagonist, 5 mmol/L,
      30 MUL) topically applied to the dorsal surface of the brainstem (n = 4)
      attenuated the responses to NTS injections of DHK (P < 0.01). The effect of DHK
      on arterial baroreflex function was examined using i.v. infusions of
      phenylephrine and nitroprusside. DHK reduced baroreflex response range (maximum
      minimum) of RSNA by 91 +/- 2% and HR by 83 +/- 5% (n = 6, P < 0.001). These
      results indicate that inhibition of GLT1 within the NTS decreases MAP, RSNA, and
      HR by the activation of ionotropic glutamate receptors. As a result, baroreflex
      control of RSNA and HR was dramatically attenuated. The astrocytic glutamate
      transporter in the NTS plays an important role in the maintenance and regulation
      of cardiovascular function.

PMID- 30230241
TI  - Determination of nitenpyram and 6-chloronicotinic acid in environmental samples
      by ion chromatography coupled with online photochemically induced fluorescence
      detector.
AB  - A simple, cost-effective, sensitive, and quick method for the determination of
      nitenpyram and its metabolite 6-chloronicotinic acid in environmental samples was
      developed by coupling an ion chromatograph with a fluorescence detector and a
      post-column photochemical reactor. This developed analytical method involved a
      rapid sample extraction by modified and miniaturized quick, easy, cheap,
      effective, rugged, and safe method followed by isocratic ion chromatographic
      separation of nitenpyram and 6-chloronicotinic acid into an IonPacTM AS11-HC
      column protected by IonPacTM AG11A guard column by running 30 mM NaOH + 10%
      acetonitrile mobile phase. A homemade post-column photochemical reactor was also
      integrated with the ion chromatographic system for online transformation of both
      analytes into their respective highly fluorescent photoproduct in basic media
      without using an extra pump. The developed method was validated by following
      SANTE/11945/2015 guidelines on analytical quality control and validation
      procedures. The method showed a good linear response (r > 0.999), improved limit
      of detection (0.101-0.132 MUg/L), minimum or no matrix effect, excellent
      recoveries (90.2-100.10%) and relative standard deviations were found to be
      <=6.50%.

PMID- 30230242
TI  - The Level of Personality Functioning Scale-Brief Form 2.0: Update of a brief
      instrument for assessing level of personality functioning.
AB  - Section III of the Diagnostic and Statistical Manual of Mental Disorders (5th
      ed.) introduced the alternative model of personality disorders that includes
      assessing levels of personality functioning. Here, we describe the development,
      preliminary psychometric evaluation and sensitivity to change of a revised brief
      self-report questionnaire, the Level of Personality Functioning Scale-Brief Form
      2.0 (LPFS-BF 2.0). Patients (N = 201) referred to a specialized centre for the
      assessment and treatment of personality disorders completed the LPFS-BF 2.0, the
      Brief Symptom Inventory and the Severity Indices of Personality Problems Short
      Form and were administered the Structured Clinical Interview for DSM-IV Axis I
      and Axis II Disorders. Internal structure and aspects of construct validity were
      examined. A subsample of 39 patients also completed the questionnaires after 3
      months of inpatient treatment. Confirmatory factor analyses demonstrated better
      fit for a two-factor solution (interpretable as self-functioning and
      interpersonal functioning) than for a unidimensional model, though acceptable
      model fit was evident only after two post hoc modifications. The LPFS-BF 2.0
      demonstrated satisfactory internal consistency and promising construct validity.
      Sensitivity to change after 3 months of treatment was high. The LPFS-BF 2.0
      constitutes a short, user-friendly instrument that provides a quick impression of
      the severity of personality pathology. (c) 2018 John Wiley & Sons, Ltd.

PMID- 30230244
TI  - Effects of Chronic NAD Supplementation on Energy Metabolism and Diurnal Rhythm in
      Obese Mice.
AB  - OBJECTIVE: Adequate nicotinamide adenine dinucleotide (NAD) content in
      hypothalamic neurons is critical for the maintenance of normal energy balance and
      circadian rhythm. In this study, the beneficial metabolic effects of chronic NAD
      supplementation on diet-induced obesity and obesity-related disruption of diurnal
      rhythms were examined. METHODS: C57BL/6 mice were fed a high-fat diet (HFD) for
      12 weeks and received an intraperitoneal injection of either saline or NAD (1
      mg/kg/day) for the last 4 weeks. The control mice were fed a chow diet and
      injected with saline for the same period. Body weights were monitored daily.
      Daily rhythms of food intake, energy expenditure, and locomotor activity were
      measured at the end of NAD treatment. The effect of NAD treatment on the clock
      gene Period 1 (PER1) transcription was also studied. RESULTS: Chronic NAD
      supplementation significantly attenuated weight gain in HFD-fed obese mice.
      Furthermore, NAD treatment recovered the suppressed rhythms in the diurnal
      locomotor activity patterns in obese mice. In addition, exogenous NAD supply
      rescued cellular NAD depletion-induced suppression of PER1 transcriptional
      activity in hypothalamic neuron cells as well as blunted daily fluctuations of
      hypothalamic arcuate nucleus PER1 expression in obese mice. CONCLUSIONS: NAD
      supplementation showed therapeutic effects in obese mice with altered diurnal
      behaviors.

PMID- 30230243
TI  - Quantitative Analysis of the Brain Ubiquitylome in Alzheimer's Disease.
AB  - Several neurodegenerative diseases including Alzheimer's Disease (AD) are
      characterized by ubiquitin-positive pathological protein aggregates. Here, an
      immunoaffinity approach is utilized to enrich ubiquitylated isopeptides after
      trypsin digestion from five AD and five age-matched control postmortem brain
      tissues. Label-free MS-based proteomic analysis identifies 4291 unique
      ubiquitylation sites mapping to 1682 unique proteins. Differential enrichment
      analysis shows that over 800 ubiquitylation sites are significantly altered
      between AD and control cases. Of these, ~80% are increased in AD, including seven
      poly ubiquitin linkages, which is consistent with proteolytic stress and high
      burden of ubiquitylated pathological aggregates in AD. The microtubule associated
      protein Tau, the core component of neurofibrillary tangles, has the highest
      number of increased sites of ubiquitylation per any protein in AD. Tau poly
      ubiquitylation from AD brain homogenates is confirmed by reciprocal co
      immunoprecipitation and by affinity capture using tandem ubiquitin binding
      entities. Co-modified peptides, with both ubiquitylation and phosphorylation
      sites, are also enriched in AD. Notably, many of the co-modified peptides mapped
      to Tau within KXGS motifs in the microtubule binding region suggesting that
      crosstalk between phosphorylation and ubiquitylation occurs on Tau in AD.
      Overall, these findings highlight the utility of MS to map ubiquitylated
      substrates in human brain and provides insight into mechanisms underlying
      pathological protein posttranslational modification in AD.

PMID- 30230245
TI  - Utility of three-dimensional models in resident education on simple and complex
      intracardiac congenital heart defects.
AB  - OBJECTIVE: Applications of three-dimensional (3D) printed models in medicine
      include preprocedure planning, patient education, and clinical training.
      Reproducing complex anatomy as a 3D printed model can be useful for understanding
      congenital heart defects (CHD). We hypothesized that using 3D printed models
      during didactic sessions with resident physicians will improve trainees'
      understanding of CHD. DESIGN AND INTERVENTION: We performed a prospective,
      randomized educational intervention for teaching pediatric and
      pediatric/emergency medicine residents about simple (ventricular septal defect
      [VSD]) and moderately complex (tetralogy of Fallot [ToF]) CHD. Residents were
      divided into two groups: intervention and control. Each group completed a
      subjective survey about their comfort with the anatomy, evaluation, and treatment
      of VSD and ToF and took an objective test on VSD and ToF. They separately
      received the same 20 min lecture, including projected two-dimensional digital
      images of VSD and ToF; the intervention group was given 3D printed models created
      using the same imaging data. After the lecture, the groups repeated the survey
      and test questions. RESULTS: Twenty-six residents participated in the VSD
      session, 34 in the ToF. There were no differences in demographics between control
      and intervention groups. All residents had higher subjective comfort with VSD and
      ToF after the lectures. There was no difference in baseline test scores for VSD
      or ToF groups. The control group scored higher on the VSD postlecture test. The
      intervention group scored higher on the ToF postlecture test. CONCLUSION:
      Incorporation of 3D printed models into lectures about CHD imparts a greater
      acute level of understanding, both subjective and objective, for pediatric and
      combined pediatric/emergency medicine residents. There does not seem to be an
      added benefit for understanding ventricular septal defects, but there is for
      tetralogy of Fallot, likely due to increased complexity of the lesion and
      difficulty visualizing spatial relationships in CHD with multiple components.

PMID- 30230246
TI  - Features and Trajectories of Eating Behavior in Weight-Loss Maintenance: Results
      from the German Weight Control Registry.
AB  - OBJECTIVE: Eating behaviors such as dietary restraint and disinhibition caused by
      emotional and external cues play a relevant role in weight-loss maintenance.
      METHODS: Four hundred forty individuals with successful weight-loss maintenance
      included in the prospective German Weight Control Registry completed the Dutch
      Eating Behavior Questionnaire. Participants were categorized into the following
      two weight groups: stable weight trajectory (WS) (n = 280) and unstable weight
      trajectory (WUS) (n = 160) over the 2-year assessment period. RESULTS: Those with
      successful weight-loss maintenance had significantly higher scores on the
      restrained and emotional eating subscales compared with a general population (GP)
      sample. At baseline, the WS individuals had lower restrained, emotional, and
      external eating scores compared with the WUS individuals. Over the 2-year follow
      up period, the trajectories of the restraint scores decreased in both groups but
      stayed elevated compared with the GP sample. Scores of the emotional and external
      eating subscales remained stable in the WS group but increased in the WUS group.
      CONCLUSIONS: A certain degree of restraint seems to be necessary for successful
      weight-loss maintenance; however, high emotional and external eating may
      counteract this effect, resulting in weight regain in the long run.

PMID- 30230248
TI  - Congenital coronary artery fistula: Presentation in the neonatal period and
      transcatheter closure.
AB  - BACKGROUND: Congenital coronary artery fistula is a rare coronary anomaly. Most
      commonly, such fistulae drain into the right side of the heart or the pulmonary
      artery. Children with coronary artery fistulae are generally asymptomatic,
      although they may have left ventricular enlargement in the setting of a moderate
      sized left to right shunt. Symptoms of congestive heart failure or ischemia are
      very rare in neonatal period, and suggest the presence of a very large shunt
      and/or coronary steal. METHODS: Single center retrospective review of
      transcatheter intervention on coronary artery fistulae presenting with symptoms
      in the neonatal period from January 2000 to March 2018. Patients with associated
      congenital heart diseases (except atrial septal defect) were excluded. Patient
      records, catheterization data, angiograms and noninvasive imaging were reviewed.
      RESULTS: Two patients underwent transcatheter intervention for symptomatic
      coronary artery fistula in the first few weeks of life. The first patient had
      multiple right and left coronary artery to right ventricle fistulae and presented
      with severe biventricular systolic dysfunction. Transcatheter closure of the
      fistulae was performed using multiple Gianturco coils. The second patient had a
      large left main coronary artery to left ventricle fistula (with left anterior
      descending and circumflex coronary artery atresia) presenting with symptoms of
      ischemia. This large fistula was closed using one Amplatzer Vascular Plug type-II
      and two Micro-Vascular Plugs. Both patients had improvement in symptoms post
      intervention and are doing well at the last follow up at 12 years and 7 months
      respectively. CONCLUSIONS: We hereby describe the rare presentation of
      symptomatic coronary artery fistulae in the neonatal period and their successful
      transcatheter management. This is also the first description of left anterior
      descending and circumflex coronary artery atresia in the setting of a large left
      main coronary artery to left ventricle fistula.

PMID- 30230247
TI  - Modification of a modulated arc total body irradiation technique: Implementation
      and first clinical experience for paediatric patients.
AB  - INTRODUCTION: To implement the modulated arc total body irradiation (MATBI)
      technique within the existing infrastructure of a radiation oncology department.
      The technique needed to treat paediatric patients of all ages, some of whom would
      require general anaesthesia (GA). METHODS: The MATBI technique required minor
      modifications to be incorporated within existing departmental infrastructure.
      Ancillary equipment essential to the technique were identified and in some cases
      custom designed to meet health and safety criteria. GA equipment was also
      considered. To evaluate the effectiveness of the implemented technique, an audit
      of the cases clinically treated was conducted. RESULTS: A motorised treatment
      couch was designed to allow the patient to be positioned in stabilisation
      equipment at a height, then lowered to the floor to accommodate source-to-skin
      distances from 180 cm to 198 cm to treat the fixed 40 cm * 40 cm field size.
      Treatment couch design also facilitated positioning of the bespoke two-part
      spoiler. While organ at risk dose is limited using a beam weight optimisation
      technique, the dose is further reduced using compensators placed close to the
      patient's skin on a 3D printed custom-made support bridge. A digital radiography
      system is used to verify compensator position. Fifteen patients have been treated
      to date for various diseases using a variety of dose fractionations ranging from
      2 Gy in a single fraction to 12 Gy in 6 fractions. Five patients have required GA
      due to age or behavioural issues. CONCLUSION: The modified MATBI technique and
      the equipment required for treatment delivery has been found to be well tolerated
      by all patients.

PMID- 30230250
TI  - Detection of piscine orthoreoviruses (PRV-1 and PRV-3) in Atlantic salmon and
      rainbow trout farmed in Germany.
AB  - Piscine orthoreoviruses (PRVs) are emerging pathogens causing circulatory
      disorders in salmonids. PRV-1 is the etiological cause of heart and skeletal
      muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar), characterized
      by epicarditis, inflammation and necrosis of the myocardium, myositis and
      necrosis of red skeletal muscle. In 2017, two German breeding farms for Atlantic
      salmon and rainbow trout (Oncorhynchus mykiss) experienced disease outbreaks with
      mortalities of 10% and 20% respectively. The main clinical signs were exhaustion
      and lethargic behaviour. During examinations, PRV-1 in salmon and PRV-3 in trout
      were detected for the first time in Germany. Further analyses also indicated the
      presence of Aeromonas salmonicida in internal tissues of both species. While PRV
      1 could be putatively linked with the disease in Atlantic salmon, most of the
      rainbow trout suffered from an infection with A. salmonicida and not with PRV-3.
      Interestingly, the sequence analysis suggests that the German PRV-3 isolate is
      more similar to a Chilean PRV-3 isolate from Coho salmon (Oncorhynchus kisutch)
      than to PRV-3 from rainbow trout from Norway. This indicates a wide geographic
      distribution of this virus or dispersal by global trade. These findings indicate
      that infections with PRVs should be considered when investigating disease
      outbreaks in salmonids.

PMID- 30230249
TI  - Primary diagnosis of ruptured biceps tendon "Baker's-type cyst" using fine needle
      aspiration biopsy: A case report.
AB  - Biceps tendon rupture is generally a clinical and radiographic diagnosis, and
      only rarely presents to the cytopathologist for fine needle aspiration biopsy. We
      present a case of ruptured biceps tendon associated with a cystic mass of the
      upper arm that was diagnosed using fine needle aspiration biopsy, and confirmed
      with subsequent MRI scan. We describe the clinical presentation, cytomorphology,
      and immunohistochemical profile of the marked chronic inflammatory infiltrate
      within the synovial fluid. We also provide a discussion of the differential
      diagnosis for a cystic mass associated with the biceps tendon on cytology.

PMID- 30230251
TI  - Fluorescence and Ultrafast Fluorescence Unveil the Formation, Folding
      Molecularity, and Excitation Dynamics of Homo-Oligomeric and Human Telomeric i
      Motifs at Acidic and Neutral pH.
AB  - i-Motifs are tetraplex DNAs known to be stable at acidic pH. The structure of i
      motifs is important in DNA nanotechnology; i-motif-forming sequences with
      consecutive cytosine (C) molecules are abundant throughout the human genome.
      There is, however, little information on the structure of C-rich DNAs under
      physiologically relevant neutral conditions. The electron dynamics of i-motifs,
      crucial to both biology and materials applications, also remains largely
      unexplored. In this work, we report a combined femtosecond and nanosecond
      broadband time-resolved fluorescence (TRF) and steady-state fluorescence
      investigation on homo-oligomer dC20 , a human telomeric sequence (HTS) 5'-dC3
      (TA2 C3 )3 , and its analogue performed with different excitation at both acidic
      and neutral pH. Our study provides direct observation of intrinsic fluorescence
      and the first full probe of the real-time dynamics of the intrinsic fluorescence
      from i-motifs formed from varied sequences and pH conditions. The results
      obtained demonstrate concrete evidence for the existence at neutral pH of i
      motifs from both dC20 and the HTS. It also identifies that, under neutral
      conditions, the i-motif from dC20 adopting the bimolecular folding structure is
      significantly more stable than the HTS i-motif featuring the unimolecular
      topology. Our femtosecond and nanosecond TRF study unveils excitation dynamics
      distinctive of the interdigitated architecture of i-motifs with the excited
      states involved exhibiting deactivation over a remarkably broad timescale through
      multiple channels involving proton-coupled electron transfer lasting tens of
      picoseconds, as signified by the solvent kinetic isotope effect, and structure
      dependent charge recombination in the hundreds of picoseconds to tens of
      nanoseconds time regime.

PMID- 30230253
TI  - Case Study: Atypical delta13 C values of urinary norandrosterone.
AB  - Isotope ratio mass spectrometry (IRMS) has been established in doping control
      analysis to identify the endogenous or exogenous origin of a variety of steroidal
      analytes including the 19-norsteroid metabolite norandrosterone (NorA). NorA can
      be found naturally in human urine in trace amounts due to endogenous
      demethylation or in situ microbial degradation. The administration of
      nortestosterone (nandrolone) or different prohormones results in the excretion of
      urinary NorA. Usually, this can be detected by IRMS due to differing delta13 C
      values of synthetic 19-norsteroids compared to endogenous reference compounds.
      The consumption of uncastrated pig edible parts like offal or even meat may also
      lead to a urinary excretion of NorA. In order to determine the delta13 C values
      of such a scenario, urine samples collected after consumption of a wild-boar
      testicle meal were analyzed. IRMS revealed highly enriched delta13 C values for
      urinary NorA, which could be related to the completely corn-based nutrition of
      the animal. Isotopic analysis of the boar's bristles demonstrated a dietary
      change from C3 -based forage, probably in winter and spring, to a C4 -based diet
      in the last weeks to months prior to death. These results supported the
      interpretation of an atypical test result of a Central European athlete's doping
      control sample with delta13 C values for NorA of -18 0/00, most probably caused
      by the consumption of a wild boar ragout. As stated before, athletes should be
      fully aware of the risk that consumption of wild boar may result in atypical or
      even adverse analytical findings in sports drug testing.

PMID- 30230252
TI  - Lifestyle Interventions Limit Gestational Weight Gain in Women with Overweight or
      Obesity: LIFE-Moms Prospective Meta-Analysis.
AB  - OBJECTIVE: This study aimed to evaluate the effects of varied lifestyle
      intervention programs designed to ameliorate excess gestational weight gain (GWG)
      in pregnant women with overweight or obesity compared with standard care,
      including effects on pregnancy outcomes. METHODS: Seven clinical centers
      conducted separate randomized clinical trials to test different lifestyle
      intervention strategies to modify GWG in diverse populations. Eligibility
      criteria, specific outcome measures, and assessment procedures were standardized
      across trials. The results of the separate trials were combined using an
      individual-participant data meta-analysis. RESULTS: For the 1,150 women
      randomized, the percent with excess GWG per week was significantly lower in the
      intervention group compared with the standard care group (61.8% vs. 75.0%; odds
      ratio [95% CI]: 0.52 [0.40 to 0.67]). Total GWG from enrollment to 36 weeks'
      gestation was also lower in the intervention group (8.1 +/- 5.2 vs. 9.7 +/- 5.4
      kg; mean difference: -1.59 kg [95% CI:-2.18 to -0.99 kg]). The results from the
      individual trials were similar. The intervention and standard care groups did not
      differ in preeclampsia, gestational diabetes, cesarean delivery, or birth weight.
      CONCLUSIONS: Behavioral lifestyle interventions focusing primarily on diet and
      physical activity among women with overweight and obesity resulted in a
      significantly lower proportion of women with excess GWG. This modest beneficial
      effect was consistent across diverse intervention modalities in a large, racially
      and socioeconomically diverse US population of pregnant women.

PMID- 30230254
TI  - Lactate administration activates the ERK1/2, mTORC1, and AMPK pathways
      differentially according to skeletal muscle type in mouse.
AB  - Skeletal muscle is described as an endocrine organ, constitutively or
      intermittently secreting bioactive molecules. The signaling pathways by which
      these molecules mediate changes in skeletal muscle and regulate interorgan
      crosstalk are only partly understood. Lactate is widely described as a signaling
      molecule in different cells, but the role of lactate as a signaling molecule in
      mature skeletal muscle has not been fully unveiled. The aim of this study was to
      determine the role of lactate on activation of signaling pathways in adult mouse
      skeletal muscle. Male mice were injected intraperitoneally with lactate or
      saline, and tissues were dissected after 40 min. Phosphorylation levels of
      relevant proteins in muscle were assessed by Western blotting. After lactate
      administration, we found an increase in p-ERK1/2Thr202/Tyr204 (3.5-fold; P =
      0.004) and p-p70S6KThr389 (1.9-fold; P = 0.01) in quadriceps; and an increase in
      p-rpS6Ser235/236 in both quadriceps (6.3-fold; P = 0.01) and EDL (2.3-fold; P =
      0.01), without changes in soleus. There was a tendency toward an increase in p
      AMPKThr172 (1.7-fold; P = 0.08), with a significant increase in p-ACCSer79 (1.5
      fold; P = 0.04) in soleus, without changes in quadriceps and EDL. These results
      support the hypothesis that lactate plays a role in the molecular signaling
      related to hypertrophy and to oxidative metabolism on adult skeletal muscle and
      suggest that this activation depends on the skeletal muscle type. The mechanisms
      that underlie the effect of lactate in mature skeletal muscles remain to be
      established.

PMID- 30230256
TI  - Recovering cellular biomass from fluids using chemical flocculation.
AB  - We developed an efficient, scalable and inexpensive method for recovering
      cellular biomass from complex fluid matrices that cannot be processed using
      conventional filtration methods. The method uses chemical flocculation with iron
      oxyhydroxides, is capable of recovering greater than 90% of cellular biomass from
      fluids with more than 103 cells ml-1 , and was validated using both mock
      communities and field samples. High quality DNA can be readily extracted from
      iron flocs using standard soil extraction kits. We applied chemical flocculation
      to fracing fluids from British Columbia, Canada and recovered a diversity of
      microbial taxa including abundant members of the Epsilon- and Deltaproteobacteria
      previously recovered from shale gas operations in the United States. Application
      of chemical flocculation presents new opportunities for scalable time-series
      monitoring and experimentation on complex fluid matrices including microbial
      community profiling and shotgun metagenomics over gas production well completion
      cycles.

PMID- 30230257
TI  - Relative and Absolute Bioavailability Study of Emicizumab to Bridge Drug Products
      and Subcutaneous Injection Sites in Healthy Volunteers.
AB  - Emicizumab (ACE910) is a bispecific antibody that is a novel, subcutaneously
      injectable treatment for patients with hemophilia A. This study assessed the
      relative bioavailability of emicizumab between old and new drug products (DPs)
      and among 3 commonly used subcutaneous injection sites (abdomen, upper arm, and
      thigh), together with its absolute bioavailability in healthy volunteers. Forty
      eight healthy volunteers were randomized into 4 groups to receive a single
      subcutaneous injection of 1 mg/kg with the old or new DP, and another 12
      volunteers each received a single, 90-minute, intravenous infusion of 0.25 mg/kg
      with the new DP. Similar pharmacokinetic profiles were observed between the DPs,
      with geometric mean ratios of 1.199 (90% confidence interval [CI] 1.060-1.355)
      for the maximum plasma concentration and 1.083 (90% CI 0.920-1.275) for area
      under the plasma concentration-time curve extrapolated to infinity. The geometric
      mean ratios of maximum plasma concentration and area under the plasma
      concentration-time curve extrapolated to infinity for upper arm versus abdomen
      were 0.823 (90% CI 0.718-0.943) and 0.926 (90% CI 0.814-1.053), respectively, and
      those for thigh versus abdomen were 1.168 (90% CI 1.030-1.324) and 1.073 (90% CI
      0.969-1.189), respectively. Absolute bioavailability ranged from 80.4% to 93.1%.
      These results suggested that no emicizumab dose adjustment would be needed when
      switching the DPs or injecting to different sites interchangeably and that
      emicizumab injected subcutaneously is highly bioavailable.

PMID- 30230255
TI  - A selective antagonist of prostaglandin E receptor subtype 4 attenuates abdominal
      aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a progressive disease that has an increasing
      prevalence with aging, but no effective pharmacological therapy to attenuate AAA
      progression is currently available. We reported that the prostaglandin E receptor
      EP4 plays roles in AAA progression. Here, we show the effect of CJ-42794, a
      selective EP4 antagonist, on AAA using two mouse models (angiotensin II- and
      CaCl2 -induced AAAs) and human aortic smooth muscle cells isolated from AAA
      tissue. Oral administration of CJ-42794 (0.2 mg/kg per day) for 4 weeks
      significantly decreased AAA formation in ApoE-/- mice infused with angiotensin II
      (1 MUg/kg per min), in which elastic fiber degradation and activations of matrix
      metalloproteinase (MMP)-2 and MMP-9 were attenuated. Interleukin-6 (IL-6)
      proteins were highly expressed in the medial layer of angiotensin II-induced
      mouse AAA tissues, whereas this expression was significantly decreased in mice
      treated with CJ-42794. AAA formation induced by periaortic CaCl2 application in
      wild-type mice was also reduced by oral administration of CJ-42794 for 4 weeks.
      After oral administration of CJ-42794 beginning 2 weeks after periaortic CaCl2
      application and continuing for an additional 4 weeks, the aortic diameter and
      elastic fiber degradation grade were significantly smaller in CJ-42794-treated
      mice than in untreated mice. Additionally, in smooth muscle cells isolated from
      human AAA tissues, stimulation of CJ-42794 inhibited PGE2 -induced IL-6 secretion
      in a dose-dependent manner and decreased PGE2 -induced MMP-2 activity. These data
      suggest that inhibition of EP4 has the potential to be a pharmacological strategy
      for attenuation of AAA progression.

PMID- 30230258
TI  - Somatic innervation contributes to the release of bulbourethral gland secretion
      in male rats.
AB  - BACKGROUND: In male rats, the bulbourethral glands (Bu-Gs) are the unique
      accessory sexual glands surrounded by striated musculature. However, until now
      the role of this musculature was unknown. OBJECTIVES: (i) To characterize the Bu
      Gs striated muscular layer in male rats and determine its innervation and
      response to genital stimulation. (ii) To reveal the role of the Bu-Gs striated
      musculature in the release of glandular secretion. (iii) To elucidate the effect
      of bilateral ablation of the Bu-Gs on copulatory behavior and seminal fluid
      characteristics. MATERIALS AND METHODS: Adult Wistar male rats were allocated in
      three experiments: in Experiment 1, the Bu-Gs striated musculature, innervation
      and reflex activity were determined by gross anatomy and histological and
      electrophysiological techniques; electromyographic activity of the Bu-Gs striated
      musculature was evoked with genital stimulation. In Experiment 2, Bu-Gs were
      analyzed after copulatory behavior of intact or animals with unilateral
      transected motor branch of the sacral plexus (MBSP). In Experiment 3, copulatory
      behavior and spermatobioscopy of males with bilateral ablation of the Bu-Gs or
      sham surgery were analyzed. RESULTS: The Bu-Gs striated fibers discharged in
      response to mechanostimulation of the prepuce, glans, and penile-urethra.
      Innervation of the Bu-Gs striated musculature originated from the MBSP; this
      nerve also innervates striated penile muscles. Unilateral transection of the MBSP
      significantly decreased the secretion from the ipsilateral Bu-G to the nerve
      transection. Bilateral ablation of Bu-Gs did not affect seminal plug formation
      but decreased semen viscosity. DISCUSSION AND CONCLUSION: The Bu-Gs striated
      musculature contributes to expel glandular secretion during sexual intercourse.
      The somatic control of Bu-Gs secretion is additional to the reported autonomic
      innervation supplied by the cavernosus nerve, which may underlie the synthesis of
      secretion as well as contraction of Bu-Gs smooth muscle.

PMID- 30230259
TI  - Sequence-based searching of custom proteome and transcriptome databases.
AB  - A long-term goal in renal physiology is to understand the mechanisms involved in
      collecting duct function and regulation at a cellular and molecular level. The
      first step in modeling of these mechanisms, which can provide a guide to
      experimentation, is the generation of a list of model components. We have curated
      a list of proteins expressed in the rat renal inner medullary collecting duct
      (IMCD) from proteomic data from 18 different publications. The database has been
      posted as a public resource at
      https://hpcwebapps.cit.nih.gov/ESBL/Database/IMCD_Proteome_Database/. It includes
      8956 different proteins. To search the IMCD Proteomic Database efficiently, we
      have created a Java-based program called curated database Basic Local Alignment
      Search Tool (cdbBLAST), which uses the NCBI BLAST kernel to search for specific
      amino acid sequences corresponding to proteins in the database. cdbBLAST reports
      information on the matched protein and identifies proteins in the database that
      have similar sequences. We have also adapted cdbBLAST to interrogate our
      previously published IMCD Transcriptome Database. We have made the cdbBLAST
      program available for use either as a web application or a downloadable .jar file
      at https://hpcwebapps.cit.nih.gov/ESBL/Database/cdbBLAST/. Database searching
      based on protein sequence removes ambiguities arising from the standard search
      method based on official gene symbols and allows the user efficient
      identification of related proteins that may fulfill the same functional roles.

PMID- 30230260
TI  - Bleeding from Wharton's duct after fine-needle aspiration biopsy on submandibular
      gland.
AB  - The case of a fine-needle aspiration biopsy (FNAB) of the patient's salivary
      gland lesions is considered a rapid, simple, reliable, minimal invasive procedure
      with markedly rare complications. Herein, we report a case of bleeding from the
      region of the Wharton's duct after a procedure of a FNAB on the patient's
      submandibular gland. To our knowledge, this is the first case of bleeding from a
      salivary duct after a FNAB. For this reason, it is important to recognize that
      bleeding from the salivary duct after a FNAB can be a rare occurrence.

PMID- 30230262
TI  - Use of a low-cost telecytopathology method for remote assessment of thyroid FNAs.
AB  - BACKGROUND: Rapid on-site evaluation is a great tool for optimizing the adequacy
      and quality of cytologic samples. The objective of the current study was to
      analyze a low-cost telecytopathology method for the remote assessment of thyroid
      fine-needle aspiration biopsies (FNABs), with comparison of the primarily
      rendered adequacy and diagnosis with the final conventional analysis. METHODS:
      Material collected from thyroid FNABs was immediately smeared onto glass slides
      and stained with Diff-Quik. A conventional microscope attached to a smart device
      was operated on-site by either a medical student or a pathology resident for Wi
      Fi transmission of the images by Skype. The cytopathologist would remotely guide
      the screening of the slides, zooming in and out of areas of interest. Remote
      assessment included an analysis of material adequacy and a preliminary diagnosis.
      The quality of the transmission and the number of slides also were recorded.
      After a washout period of 3 weeks, final diagnosis and adequacy were assigned by
      conventional microscopy. RESULTS: The final agreement rate for adequacy between
      remote and conventional analysis was 90.5%. For diagnosis, the final agreement
      rate was 83.3%. The diagnosis agreement rate varied, depending on the quality of
      transmission: there was 88% agreement when the quality was excellent, 77.8%
      agreement when it was good, and 62.5% agreement when it was poor. CONCLUSIONS:
      Low-cost telecytopathology is an efficient method for the remote assessment of
      thyroid FNAB adequacy and diagnosis. The wide use of such technology in low
      resource or remote centers may have a positive impact on the number of adequate
      or satisfactory samples, optimizing the management of patients who have thyroid
      nodules.

PMID- 30230261
TI  - PKCalpha replaces AMPK to regulate mitophagy: Another PEDF role on ischaemic
      cardioprotection.
AB  - Both decreased autophagy positive regulator AMP activated protein kinase (AMPK)
      level and promoted mitophagy are observed in oxygen-glucose deprivation (OGD)
      cardiomyocytes treated with pigment epithelium-derived factor (PEDF). This
      contradictory phenomenon and its underlying mechanisms have not been thoroughly
      elucidated. Our previous study reveals that PEDF increases the protein kinase
      Calpha (PKCalpha) and phospho-PKCalpha (p-PKCalpha) contents to promote
      mitophagy. Thus, we investigated the association between PKCalpha and mitophagy.
      Here we identify an interaction between PKCalpha and Unc-51-like kinase 1 (ULK1),
      essential component of mitophagy. Further analyses show this is a direct
      interaction within a domain of ULK1 that termed the serine/threonine-rich domain
      (S/T domain). Notably, a deletion mutant ULK1 that lacks the binding domain is
      defective in mediating PEDF-induced mitophagy. Furthermore, we demonstrate that
      ULK1 is phosphorylated at Ser317/555/777 and Raptor is also phosphorylated by
      phospho-PKCalpha. Phospho-ULK1 (p-ULK1) at these sites are all essential for PEDF
      induced mitophagy and reduce the release of mitochondrial ROS and DNA. This study
      therefore identifies a previously uncharacterized interaction between the ULK1
      and PKCalpha that can replace the AMPK-dependent mitophagy processes.

PMID- 30230264
TI  - Protease inhibitors: recent advancement in its usage as a potential biocontrol
      agent for insect pest management.
AB  - Plant-derived protease inhibitors (PIs) are a promising defensin for crop
      improvement and insect pest management. Although agronomist made significant
      efforts in utilizing PIs for managing insect pests, the potentials of PIs are
      still obscured. Insect ability to compensate nutrient starvation induced by
      dietary PI feeding using different strategies, that is, overexpression of PI
      sensitive protease, expression of PI-insensitive proteases, degradation of PI,
      has made this innumerable collection of PIs worthless. A practical challenge for
      agronomist is to identify potent PI candidates, to limit insect compensatory
      responses and to elucidate insect compensatory and resistance mechanisms
      activated upon herbivory. This knowledge could be further efficiently utilized to
      identify potential targets for RNAi-mediated pest control. These vital genes of
      insects could be functionally annotated using the advanced gene-editing
      technique, CRISPR/Cas9. Contemporary research is exploiting different in silico
      and modern molecular biology techniques to utilize PIs in controlling insect
      pests efficiently. This review is structured to update recent advancements in
      this field, along with its chronological background.

PMID- 30230263
TI  - Pharmacokinetics, Excretion, and Mass Balance of [14 C]-Batefenterol Following a
      Single Microtracer Intravenous Dose (Concomitant to an Inhaled Dose) or Oral Dose
      of Batefenterol in Healthy Men.
AB  - Inhaled batefenterol is an investigational bifunctional molecule for the
      treatment of chronic obstructive pulmonary disease. The excretion balance and
      pharmacokinetics of batefenterol using [14 C]-radiolabeled drug administered
      orally and as intravenous (IV) infusion were assessed. In this 2-period, open
      label study, 6 healthy male subjects received a single IV microtracer 1-hour
      infusion of 4 MUg [14 C]-batefenterol concomitant with inhaled nonradiolabeled
      batefenterol (1200 MUg) followed by oral [14 C]-batefenterol (200 MUg) in period
      2 after a 14-day washout. The primary end points included: the area under the
      concentration-time curve from time zero to last time of quantifiable
      concentration (AUC0-t ); maximum observed concentration (Cmax ); and time of
      occurrence of maximum observed concentration. Following IV administration, the
      geometric mean AUC0-t of [14 C]-batefenterol was 121.9 pgEq * h/mL; maximum
      observed concentration and time of occurrence of maximum observed concentration
      were 92.7 pgEq/mL and 0.8 hours, respectively; absolute oral bioavailability was
      0.012%. The mean AUC0-t ratio indicated that [14 C]-batefenterol accounted for
      85% of total circulating radioactivity in the plasma initially and declined
      rapidly following IV administration, but only ~0.2% of total circulating
      radioactivity following oral administration. Cumulative mean recovery of total
      radioactive [14 C]-batefenterol in urine and feces was 6.31% and 77.6%,
      respectively. Overall, batefenterol exhibited low systemic bioavailability after
      inhaled and oral administration, and high fecal excretion and low urinary
      excretion following IV and oral administration.

PMID- 30230265
TI  - Carbon dioxide CT angiography during endovascular treatment of bilateral common
      iliac disease with angio-CT utilisation.
AB  - This paper presents the application of carbon dioxide for CT imaging during an
      endovascular procedure to help characterise unexpected bilateral common iliac
      artery stenosis utilising an angio-CT system, confirming its application in
      interventional radiology while maintaining sterility. A 78 year old male was
      referred to the Radiology Interventional Suite with left lower limb rest pain. On
      imaging via digital subtraction angiography and CT utilising both iodinated
      contrast and carbon-dioxide (CO2 ), endovascular treatment of bilateral CIA
      stenosis was performed with good clinical result. The case presented demonstrates
      the advanced imaging techniques possible in suites that have ready access to
      angiography and conventional CT. CO2 CT angiography is optimally performed on
      combined Angio-CT systems where CT and angiography system are integrated into a
      single room.

PMID- 30230267
TI  - Presence of chromosomal abnormalities in fetuses with isolated ventriculomegaly
      on prenatal ultrasound in China.
AB  - BACKGROUND: The purpose of our study was to compare the incidence of chromosomal
      abnormalities of fetuses with isolated fetal ventriculomegaly (VM) to that of
      fetuses with the sole risk factor of being born to mothers of advanced age.
      METHOD: This prospective study included two groups. Group 1 included fetuses with
      isolated VM and were further categorized according to maternal age, fetal gender,
      laterality of VM (unilateral or bilateral), evolution of VM (resolved or
      persistent or progressive), and the gestational age at the time of diagnosis
      (<28w or >=28w). Group 2 were fetuses without any fetal structural abnormality,
      but maternal age was at or over 35 years. RESULT: Eighteen fetuses (18/231, 7.8%)
      with chromosomal abnormalities were identified for Group 1, and 13 fetuses
      (13/782, 1.7%) were identified for Group 2. When cases with mothers of advanced
      age were excluded from Group 1, the incidence of chromosomal abnormalities of
      isolated VM fetuses age was 7.2%, which is still higher than that of normal
      structural fetuses in mothers of advanced age (p < 0.001). CONCLUSION: The risk
      of chromosomal abnormalities for fetuses with isolated VM is high, especially
      when it is severe, bilateral, the first presence occurs in mid-gestation and is
      not resolved.

PMID- 30230266
TI  - Immunomodulatory placental-expanded, mesenchymal stromal cells improve muscle
      function following hip arthroplasty.
AB  - BACKGROUND: No regenerative approach has thus far been shown to be effective in
      skeletal muscle injuries, despite their high frequency and associated functional
      deficits. We sought to address surgical trauma-related muscle injuries using
      local intraoperative application of allogeneic placenta-derived, mesenchymal-like
      adherent cells (PLX-PAD), using hip arthroplasty as a standardized injury model,
      because of the high regenerative and immunomodulatory potency of this cell type.
      METHODS: Our pilot phase I/IIa study was prospective, randomized, double blind,
      and placebo-controlled. Twenty patients undergoing hip arthroplasty via a direct
      lateral approach received an injection of 3.0 * 108 (300 M, n = 6) or 1.5 * 108
      (150 M, n = 7) PLX-PAD or a placebo (n = 7) into the injured gluteus medius
      muscles. RESULTS: We did not observe any relevant PLX-PAD-related adverse events
      at the 2-year follow-up. Improved gluteus medius strength was noted as early as
      Week 6 in the treatment-groups. Surprisingly, until Week 26, the low-dose group
      outperformed the high-dose group and reached significantly improved strength
      compared with placebo [150 M vs. placebo: P = 0.007 (baseline adjusted; 95%
      confidence interval 7.6, 43.9); preoperative baseline values mean +/- SE:
      placebo: 24.4 +/- 6.7 Nm, 150 M: 27.3 +/- 5.6 Nm], mirrored by an increase in
      muscle volume [150 M vs. placebo: P = 0.004 (baseline adjusted; 95% confidence
      interval 6.0, 30.0); preoperative baseline values GM volume: placebo: 211.9 +/-
      15.3 cm3 , 150 M: 237.4 +/- 27.2 cm3 ]. Histology indicated accelerated healing
      after cell therapy. Biomarker studies revealed that low-dose treatment reduced
      the surgery-related immunological stress reaction more than high-dose treatment
      (exemplarily: CD16+ NK cells: Day 1 P = 0.06 vs. placebo, P = 0.07 vs. 150 M;
      CD4+ T-cells: Day 1 P = 0.04 vs. placebo, P = 0.08 vs. 150 M). Signs of late
      onset immune reactivity after high-dose treatment corresponded to reduced
      functional improvement. CONCLUSIONS: Allogeneic PLX-PAD therapy improved strength
      and volume of injured skeletal muscle with a reasonable safety profile. Outcomes
      could be positively correlated with the modulation of early postoperative stress
      related immunological reactions.

PMID- 30230268
TI  - Status of population-based birth defects surveillance programs before and after
      the Zika public health response in the United States.
AB  - BACKGROUND: The 2016 Zika public health response in the United States highlighted
      the need for birth defect surveillance (BDS) programs to collect population-based
      data on birth defects potentially related to Zika as rapidly as possible through
      enhanced case ascertainment and reporting. The National Birth Defects Prevention
      Network (NBDPN) assessed BDS program activities in the United States before and
      after the Zika response. METHODS: The NBDPN surveyed 54 BDS programs regarding
      activities before and after the Zika response, lessons learned, and programmatic
      needs. Follow-up emails were sent and phone calls were held for programs with
      incomplete or no response to the online survey. Survey data were cleaned and
      tallied, and responses to open-ended questions were placed into best-fit
      categories. RESULTS: A 100% response rate was achieved. Of the 54 programs
      surveyed, 42 reported participation in the Zika public health response that
      included BDS activities. Programs faced challenges in expanding their
      surveillance effort given the response requirements but reported mitigating
      factors such as establishing and enhancing partnerships and program experience
      with surveillance and clinical activities. Beyond funding, reported program needs
      included training, surveillance tools/resources, and availability of clinical
      experts. CONCLUSIONS: Existing BDS programs with experience implementing active
      case-finding and case verification were able to adapt their surveillance efforts
      rapidly to collect and report data necessary for the Zika response. Program
      sustainability for BDS remains challenging; thus, continued support, training,
      and resource development are important to ensure that the infrastructure built
      during the Zika response is available for the next public health response.

PMID- 30230269
TI  - Susceptibility of placental mitochondria to oxidative stress.
AB  - BACKGROUND: Two different mitochondrial fractions (MFs) have been characterized
      in the human placenta: the "light" and "heavy" fractions (LMF and HMF). Although
      these organelles are the main source of reactive oxygen species, an imbalance
      between their production and the rate of detoxification represents a serious
      threat to mitochondrial homeostasis and, in the case of the placenta, also to the
      fetus. The aim of this study was to evaluate the antioxidant capacity and
      susceptibility to oxidative stress in both types of MFs. METHODS: Human MFs were
      isolated from healthy donors (n = 11) and either incubated or not with H2 O2 .
      Catalase (CAT) activity, and reduced glutathione (GSH), lipid peroxidation (LP),
      and protein carbonylation (PC) levels were determined. RESULTS: H2 O2 treatment
      increased LP and PC levels and decreased CAT activity. GSH levels were similar in
      control and treated MFs. CONCLUSION: H2 O2 caused oxidative damage in both LMF
      and HMF and the antioxidant system measured in these two MFs responded similarly.
      To the best of our knowledge, this is the first partial description of the
      antioxidant defense in placental HMF and LMF performed in a cell-free assay. The
      small number of antioxidant system parameters measured did not allow detecting
      differences between HMF and LMF.

PMID- 30230270
TI  - Road-killed mammals provide insight into tick-borne bacterial pathogen
      communities within urban habitats.
AB  - Small- and medium-sized mammals play an important role in the life cycle of tick
      borne pathogens in urban habitats. Our aim was to apply the general protocol,
      DAMA (documentation-assessment-monitoring-action), which is an integrated
      proposal to build a proactive capacity to understand, anticipate, and respond to
      the outcomes of accelerating environmental change. Here we tested whether road
      killed carcasses in urban areas are useful sources of tissue and parasite samples
      to investigate these species' contribution to the epidemiology of vector-borne
      diseases. We collected 29 road-killed and 6 carcasses with different causes of
      mortality (23 northern white-breasted hedgehogs and 12 from seven other mammal
      species) mainly from Budapest, Hungary. We used quantitative and conventional
      PCRs to determine pathogens in 90 collected tissues (52 from hedgehogs; 38 from
      other species) and 417 ticks that were only found on hedgehogs. Tissue samples
      revealed a wide range of bacteria including human zoonotic pathogens identified
      as Anaplasma phagocytophilum ecotype I, Borrelia afzelii, B. spielmanii, Borrelia
      miyamotoi, Rickettsia helvetica, and Bartonella species. Among the 23 collected
      hedgehog carcasses, 17 (74%) were infected with A. phagocytophilum, 6 (26%) with
      Borrelia burgdorferi s.l., 12 (52%) with R. helvetica, and 15 (65%) with
      Rickettsia sp. Furthermore, we report the first detection of Rickettsia sp.
      infection in European moles and lesser weasel and R. helvetica in stone marten.
      Through sequencing B. afzelii, R. helvetica, R. monacensis and A. phagocytophilum
      ecotype I were identified in the ticks removed from the carcasses. We showed that
      road-killed urban mammal species are exposed to multiple tick-borne pathogens but
      further studies have to clarify whether they, in fact, also have a role in their
      maintenance and spread. Our study also demonstrates that roadkill can be used in
      the risk assessment of potential human infection and in the implementation of the
      DAMA protocol.

PMID- 30230271
TI  - Novel In Situ Gelling Hydrogels Loaded with Recombinant Collagen Peptide
      Microspheres as a Slow-Release System Induce Ectopic Bone Formation.
AB  - New solutions for large bone defect repair are needed. Here, in situ gelling slow
      release systems for bone induction are assessed. Collagen-I based Recombinant
      Peptide (RCP) microspheres (MSs) are produced and used as a carrier for bone
      morphogenetic protein 2 (BMP-2). The RCP-MSs are dispersed in three hydrogels:
      high mannuronate (SLM) alginate, high guluronate (SLG) alginate, and
      thermoresponsive hyaluronan derivative (HApN). HApN+RCP-MS forms a gel structure
      at 32 oC or above, while SLM+RCP-MS and SLG+RCP-MS respond to shear stress
      displaying thixotropic behavior. Alginate formulations show sustained release of
      BMP-2, while there is minimal release from HApN. These formulations are injected
      subcutaneously in rats. SLM+RCP-MS and SLG+RCP-MS loaded with BMP-2 induce
      ectopic bone formation as revealed by X-ray tomography and histology, whereas
      HApN+RCP-MS do not. Vascularization occurs within all the formulations studied
      and is significantly higher in SLG+MS and HApN+RCP-MS than in SLM+RCP-MS.
      Inflammation (based on macrophage subset staining) decreases over time in both
      alginate groups, but increases in the HApN+RCP-MS condition. It is shown that a
      balance between inflammatory cell infiltration, BMP-2 release, and
      vascularization, achieved in the SLG+RCP-MS alginate condition, is optimal for
      the induction of de novo bone formation.

PMID- 30230273
TI  - Clinical epidemiology of congenital heart disease in Nigerian children, 2012
      2017.
AB  - BACKGROUND: Congenital heart diseases (CHDs) affect ~1% of newborns and are a
      significant cause of morbidity and mortality in children. We present the clinical
      epidemiology of CHD as seen in a large university medical center in Nigeria.
      METHODS: Participants were 767 children with echocardiographically confirmed CHD
      seen over a 5-year period at the Lagos University Teaching Hospital, Nigeria.
      RESULTS: Clinical presentation was often late with just over half (58.1%)
      presenting in infancy. The male:female distribution was 1:1. The predominant
      types of cardiac lesion seen were septal defects (43%), conotruncal defects
      (23.7%), atrioventricular septal defects (9.8%), and right ventricular outflow
      tract obstruction (7.3%). Cyanotic CHD was seen in 28.4% of cases and the single
      most common cyanotic CHD was Tetralogy of Fallot (13.4%). Children with cyanotic
      CHD were older (p = .002), had more severe lesions (p < .0001) and were more
      likely to have cardiac intervention (p < .0001). Extracardiac malformations were
      present in nearly one-third of the children. Syndromes associated with CHD were
      identified in 15.5% of the children and included Down syndrome (11.9%),
      congenital rubella syndrome (1.0%), and Marfan syndrome (0.7%). CONCLUSIONS: This
      study is a large case series of CHD from a single site in sub-Saharan Africa
      utilizing clinical, epidemiological, and developmental considerations. It
      provides a rich and up-to-date description of the clinical epidemiology of CHD in
      Nigerian children while yielding data that could be useful for designing genetic,
      molecular, and biomarker studies.

PMID- 30230274
TI  - WE ARE AGENTS OF CHANGE.

PMID- 30230272
TI  - Ambient particulate matter enhances the pulmonary allergic immune response to
      house dust mite in a BALB/c mouse model by augmenting Th2- and Th17-immune
      responses.
AB  - Ambient particulate matter (PM) exacerbates airway inflammation and hyper
      reactivity in asthmatic patients. Studies show that PM has adjuvant-like
      properties that enhance the allergic inflammatory response; however, the
      mechanisms through which PM enhances these processes remain elusive. The
      objective of the study was to examine how ambient PM enhances the allergic immune
      response. Eight-week-old BALB/c mice were sensitized with house dust mite (HDM)
      or HDM and ambient particulate matter (PM, 2.5 MUm; Sacramento, CA) to assess how
      PM modulates the development of adaptive immune responses against allergens. Both
      groups were challenged with HDM only. Bronchoalveolar lavage (BAL) was analyzed
      for extent of airway inflammation. Lung tissue was used for histological
      analysis, mucosubstance quantification, and heme oxygenase-1 (HO-1)
      localization/quantification. Gene expression was analyzed in whole lung to
      characterize immune markers of inflammation: cytokines, chemokines, antioxidant
      enzymes, and transcription factors. Cytokine and chemokine protein levels were
      quantified in whole lung to confirm gene expression patterns. Compared to HDM
      only sensitization, exposure to PM during HDM sensitization led to significant
      immune cell recruitment into the airway subepithelium, IgE gene expression,
      mucosubstance production, and Th2-associated cytokine expression. HO-1 levels
      were not significantly different between the treatment groups. Gene expression
      profiles suggest that polycyclic aromatic hydrocarbon (PAH) content in PM
      activated the aryl hydrocarbon receptor (AhR) and enhanced Th17-responses in the
      mice that received HDM and PM compared to mice that received HDM-only. The
      findings suggest that PM enhances allergic sensitization via enhancement of Th2
      mediated inflammation and that AhR activation by PAHs in PM promotes Th17-immune
      responses.

PMID- 30230276
TI  - UNDERSTANDING THE IBM COMPLAINT PROCESS.

PMID- 30230275
TI  - ADVOCATING TO SHAPE THE FUTURE OF HEALTH CARE.

PMID- 30230277
TI  - LIFTOFF FOR THE MOONSHOT INITIATIVE.

PMID- 30230278
TI  - INVESTING IN INFRASTRUCTURE TO PRODUCE THE BEST PHYSICIANS.

PMID- 30230279
TI  - IHC'S COMPASS PRACTICE TRANSFORMATION NETWORK: HELPING PHYSICIANS TRANSITION TO
      VALUE-BASED PAYMENT.

PMID- 30230280
TI  - WHAT TO DO WITH YOUR EXTRA DOLLARS.

PMID- 30230281
TI  - A CLARION CALL FROM 1958.

PMID- 30230282
TI  - TO MAKE AN END IS TO MAKE A BEGINNING.

PMID- 30230284
TI  - CANDOR PILOT SITE A SUCCESS IMS receives grant tofurther Candor education.

PMID- 30230283
TI  - A PRESCRIPTION FOR PROFESSIONAL BURNOUT.
AB  - In the closing months of 2016, my work with the Iowa Medical Society gave me the
      privilege of visiting with many fellow physicians across our wonderful state. If
      is a deep honor to meet with colleagues who are so committed to the well-being of
      their patients, their communities, and our profession. Simultaneously, I am
      concerned to hear the all-too-common tales of exhaustion, stress, and frustration
      at work - classic signs of professional burnout.

PMID- 30230285
TI  - RENEWING PASSION AND PURPOSE IN PRACTICE.

PMID- 30230286
TI  - A NATIONAL UPSET The Remedy Starts Here.
AB  - When I penned this article in November, I was enamored by the improbable upset in
      the contest that stunned the pundits. Who would have believed Iowa could shock
      the heavily favored and 3rd- ranked Michigan Wolverines football team in a 14-to
      13 win? It was another historic November to remember, and Iowa was at the heart
      of it all. After the fans stormed the field with celebratory fervor, it was time
      to get back to business and reflect on the past to plan a course for the future.

PMID- 30230287
TI  - CONTENT MARKETING How Your Medical Practice Can Benefit.

PMID- 30230288
TI  - Practical impressions of interpretative phenomenological analysis from the
      novice's standpoint.
AB  - BACKGROUND: Interpretative phenomenological analysis (IPA) is an approach to
      qualitative analysis that has increasingly been used in health and psychology
      over the past 10-15 years. AIM: To address the practical impressions of applying
      IPA, from the perspective of novice researchers. DISCUSSION: The authors have
      observed two areas to which they would like to draw novice researchers'
      attention: interpretations of the six steps of IPA and what 'interpretation'
      means in IPA. They provide tentative suggestions in these areas for supporting
      researchers new to IPA. CONCLUSION: More transparency in analysis when publishing
      work, alongside the introduction of interpretation as the 'seventh' step of IPA,
      may increase the quality of IPA research and help new researchers to understand
      the approach better.

PMID- 30230289
TI  - Assessment, prevention and treatment of faecal incontinence in older people.
AB  - Faecal incontinence is an impaired ability to control the passage of stool, often
      described as involuntary loss of solid or liquid stool, and the symptom of an
      underlying diagnosis. It is a common problem in older adults. Although not a life
      threatening condition, it can have a significant negative effect on an
      individual's quality of life and adverse medical, social and economic
      consequences. Due to the taboo and stigmatising nature of the condition many
      individuals do not seek assistance. Healthcare professionals should take every
      opportunity to ask about faecal incontinence symptoms so that symptomatic relief
      and treatment interventions can be initiated. There are several conservative
      approaches available for the treatment of faecal incontinence, which should be
      considered as first line to target symptomatic relief.

PMID- 30230290
TI  - Fetal Myelomeningocele After Maternal Methotrexate Administration: A Case Report.
AB  - Background: Folate supplementation in women of reproductive age has a well
      established role in the prevention of neural tube defects. Methotrexate is a
      commonly used drug which functions by inhibiting normal folate metabolism in
      active cells. An association between fetal methotrexate exposure and
      myelomeningocele might be expected, considering this relationship. However, to
      our knowledge, no cases of myelomeningocele secondary to in utero methotrexate
      exposure have been reported. Case: We present the case of a gravid patient who,
      having received methotrexate for management of an ectopic pregnancy, was lost to
      follow-up and returned several weeks later carrying an intrauterine pregnancy.
      The fetus was found prenatally to be suffering from multiple congenital
      anomalies. At birth the infant demonstrated many of the abnormalities commonly
      associated with fetal methotrexate syndrome, including craniosynostosis and
      talipes equinovarus. Most interestingly, the newborn was also diagnosed with a
      lumbar myelomeningocele and concomitant type II Chiari malformation, as is often
      associated with such a neural tube defect. Conclusion: Methotrexate exposure may
      impact the fetal risk of myelomeningocele. Patients should be counseled
      thoroughly on the importance of follow-up care.

PMID- 30230291
TI  - Squamous Cell Carcinoma of the Vulva Presenting as an Isolated Inguinal Lymph
      Node Metastasis: A Case Report.
AB  - Background: Vulvar carcinoma is usually diagnosed after a patient notices
      bleeding, pruritis, or a lesion. We describe a case of vulvar carcinoma
      presenting as an isolated lymph node metastasis in the setting of negative pelvic
      examinations, with interval development of a vulvar lesion. Case: A 45-year-old
      woman presented with a left groin mass, and a biopsy revealed squamous cell
      carcinoma of unknown primary. She underwent an extensive work-up including
      several evaluations by gynecologic oncologists, all with negative results. Only
      after 11 months of clinical monitoring did a vulvar lesion appear and the primary
      tumor was diagnosed. Conclusion: Cancers of unknown primary site presenting in an
      inguinal lymph node are relatively rare. Vulvar carcinoma should remain in the
      differential diagnosis even in the setting of a previously negative pelvic
      examination.

PMID- 30230292
TI  - Intrasphincteric Botulinum Toxin Injections to Treat Achalasia Diagnosed in 615
      Pregnancy: A Case Report.
AB  - Background: Achalasia is an esophageal smooth muscle disorder characterized by
      failure of the lower esophageal sphincter to relax with swallowing. Case: A 17
      year-old primigravid woman with an intrauterine pregnancy at 31+3 weeks reported
      an unintentional 22.5 kg weight loss in 2 years. Her body mass index was 15.9.
      Her symptoms included nausea, regurgitation, and worsening dysphagia. MRI
      suggested achalasia. She was started on total parenteral nutrition until she
      developed bacteremia. An esophagogastroduodenoscopy with Duotube placement and
      botulinum toxin A injections were performed. Tube feeds were initiated and
      continued until the Duotube became obstructed. The patient delivered at 37+4
      weeks with mild preeclampsia. A postpartum barium swallow test indicated
      achalasia. Conclusion: A history of dysphagia to solids and/or liquids with
      weight loss should raise clinical suspicions for achalasia.

PMID- 30230293
TI  - Long-term oncologic and functional outcomes after robot-assisted partial
      nephrectomy in elderly patients.
AB  - BACKGROUND: The aim of this study was to assess the long-term oncologic and
      functional outcomes in elderly patients having undergone robot-assisted partial
      nephrectomy (RAPN) for renal cancer (RC). METHODS: Sixty one patients out of 323
      who underwent RAPN for localized RC between July 2009 and March 2016 in our high
      volume robotic surgery center (>800 procedures/year), had 70 years or more.
      Inclusion criteria of the study were age >=70 years; pathological confirmed RCC
      and ASA score <=3. All patients were stratified according to PADUA classification
      system in three groups: < 7 points, 8-9 points, > 10 points. Trifecta was defined
      as a warm ischemia time (WIT) less then 25min, negative surgical margins and no
      perioperative complications. RESULTS: A total of 52 patients were included;
      median follow-up was 47 months. Median age was 74 yrs. (IQR 72-76.5).
      Complication rate was 15.4%. Trifecta failure was associated to PADUA score
      (p=0.02), and tumor diameter (p=0.04). Renal function was altered in 10 (19.2%)
      patients before surgery and at last follow-up in 11 (21.1%) patients (CKD
      stage>2) The DFS, OS and CSS were 89.33%, 90.06% and 94.4%, respectively.
      CONCLUSIONS: In a high-volume center, robot-assisted approach is feasible and
      safe in surgical fit elderly patients with good long-term oncologic outcomes.

PMID- 30230294
TI  - Adherence to hormonal deprivation therapy in prostate cancer in clinical
      practice: a retrospective, single-centre study.
AB  - BACKGROUND: Androgen-deprivation therapy is one of the options available for
      treating both advanced and metastatic prostate cancer (PCa). It is used as an
      adjuvant or neoadjuvant therapy, either alone or in combination with radiotherapy
      (RT) or surgery. The aim of this study is to appraise adherence to ADT. METHODS:
      A total of 136 PCa patients on ADT (leuprorelin, triptorelin, and degarelix) were
      monitored between January 2008 and December 2015. Demographic, histopathological,
      and clinical data were collected. RESULTS: Mean age was 76 years and PSA was 91.9
      ng/ml. Forty-six patients (34%) had a Gleason score >7. One hundred and eight
      patients were treated exclusively with ADT (53 (49%) leuprorelin, 45 (42%)
      triptorelin, and 10 (9%) degarelix). Mean follow-up was 3.5 years, with a mean
      overall prescription time of 3.4 years. Adherence to ADT was 95%. Sixty-three
      patients are currently on therapy, while 45 have discontinued treatment. Reasons
      for discontinuation were death (56%), physician's choice (33%), and patient's
      preferences (11%). CONCLUSIONS: Adherence to ADT was optimal, probably owing to
      its balanced side effect and benefit profile. Patient's death was the most
      frequent reason for discontinuation.

PMID- 30230295
TI  - Cigarette smoking is not associated with prostate cancer diagnosis and
      agressiveness: a cross sectional italian study.
AB  - BACKGROUND: The aim of our study is to explore the association between cigarette
      smoking and the risk of prostate cancer (PCa) diagnosis as well as high grade
      disease in men undergoing prostate biopsies. METHODS: From 2008 to 2016, we
      prospectively enrolled a consecutive series of men with no history of PCa
      undergoing prostate biopsies. Variables assessed the day of the biopsy included:
      Family history of PCa, age, body mass index (BMI), comorbidities, digital rectal
      examination (DRE), prostate volume, PSA, free PSA, smoking status, number of
      cigarette/day, smoking time, smoking starting age and smoking cessation. Smoking
      variables were evaluated as predictors of PCa and high grade PCa (Prognostic
      Grade Group >= 3) using adjusted logistic regression analyses. RESULTS: Overall
      1080 patients were enrolled, out of them 499/1080/753 (46%) had never smoked;
      168/1080/753 (16%) were smokers and 413/1080 (38%) were former smokers. Out of
      the 451/1080 (41%) patients with PCa 175/451 (39%) presented high grade disease.
      As expected family history, age, dyslipidaemia, PSA, digital rectal examination
      and prostate volume were independent predictors of PCa. As well age, DRE, and PSA
      were independent predictors of high-grade disease. Smoking status (OR=0.983; CI:
      0.689-1.402) and the associated variables were not independent predictors of PCa
      or high grade PCa (OR:1.250; CI:0.593-1.327). CONCLUSIONS: In our cross-sectional
      study, smoking is not predictive of PCa or high-grade disease. Further studies
      should evaluate if smoking could influence PCa diagnosis and aggressiveness.

PMID- 30230296
TI  - Risk factors and prognostic implications for pathologic upstaging to T3a after
      partial nephrectomy.
AB  - BACKGROUND: Performing a partial nephrectomy (PN) on a cT1 tumor, which post-
      operatively is upgraded to pT3a can possibly lead to compromise of cancer
      specific mortality. We therefore aimed to identify risk factors for pathologic
      T3a upstaging of cT1 tumors and to analyze the association between upstaging,
      positive surgical margins (PSM) and overall survival (OS). METHODS: The present
      study included patients who underwent PN for a clinically localized T1 renal mass
      from 2 datasets: (1) 1,298 patients from a prospectively maintained multi-center
      database (MCDB) and (2) 7,940 patients from the National Cancer Database (NCDB).
      Multivariable logistic regression models within each cohort were used to identify
      predictors of cT1 to pT3a upstaging and its association with PSM. Cox proportion
      hazards regression models were used to compare overall survival in the NCDB
      cohort. RESULTS: The rate of pT3a upstaging was 5.7% (n=74) in the MCDB and 1.9%
      (n=156) in the NCDB cohort. Older age (MCDB OR=1.04, p=.001; NCDB OR=1.04,
      p=.001) and larger tumor size (MCDB OR=1.89, p<.001; NCDB OR=1.38, p<.001)
      increased the likelihood of upstaging. PSM was found to be more likely for pT3a
      upstaged patients in both cohorts (MCDB 14.9% vs. 3.5%, p<.001; NCDB 14.8% vs.
      8.3%, p=.006), even when adjusting for tumor size. At short term follow-up (NCDB
      median follow-up 27.3 months), pT3a upstaging was associated with worse OS in
      univariable (HR=1.89; 95% CI=1.00, 3.55; p=.049) but not multivariable analysis
      (HR=1.63; 95% CI=0.86, 3.08; p=.131). OS was 93.0% vs. 95.8% at 3 years for those
      with and without pT3a upstaging, respectively. CONCLUSIONS: Larger tumor size and
      increased age are associated with pathological upstaging to T3a for clinical T1
      tumors treated with partial nephrectomy. Steps to improve identification of
      occult pT3a disease are necessary as its occurrence significantly increased the
      likelihood of a PSM, both in a high volume multicenter cohort, as well as, a
      national data registry.

PMID- 30230297
TI  - New insight in penile cancer.
AB  - Penile cancer is a rare disease. Most of penile cancer are squamous cell
      carcinoma. Diagnosis is based on self-examination, clinical examination and
      confirmatory biopsy. Several imaging technique could be used for staging purpose.
      However, the best modality for staging in intermediate and high risk patients is
      by surgical evaluation and the use of inguinal lymph node dissection, that has
      also a therapeutic effect. Unfortunately, inguinal lymph node dissection is
      underused. Penile cancer treatment may have a major adverse impact on urinary and
      sexual function and on quality of life. Penile-sparing surgery and radiation
      therapies are available, and in selected patients offer good outcomes with
      acceptable rates of local recurrence. Penile-sparing surgery should be preferred
      when indicated. Follow-up with periodical controls is mandatory up to 5 years.
      However, risk of local, nodal and distant recurrence after 5 years was reported.
      Imaging is not routinely recommended during follow-up. Patients should be trained
      to self-examination during the follow-up.

PMID- 30230298
TI  - Fluoroscopy-free technique is reliable and safe in retrograde intrarenal surgery.
AB  - BACKGROUND: Traditional retrograde intrarenal surgery is performed under
      fluoroscopic guidance. In the present study, we assessed the efficacy and safety
      of retrograde intrarenal surgery without fluoroscopic guidance in selected
      patients with renal and proximal ureteral stone disease. METHODS: Between October
      2013 and August 2016, a total of 350 patients who underwent retrograde intrarenal
      surgery for upper urinary tract stone disease were retrospectively analyzed.
      Ninetyfive (Group 1) and 255 (Group 2) patients underwent retrograde intrarenal
      surgery with and without fluoroscopy guidance, respectively. We documented
      complications and success rates of the procedures retrospectively. RESULTS: The
      mean age of the patients was 45.3 years. The mean stone size was 14.5+/-5.5 (530)
      mm and 13.7+/-5.2 (430) mm in Group 1 and 2, respectively (p=0.197). The stone
      free rates one month after surgery were 86.3% and 87% in Group 1 and 2,
      respectively (p=0.739). The overall incidence of intraoperative complication was
      16.3%. In Group 1, incidence of intraoperative complication was 17.9% (n=17)
      while in Group 2 incidence was 15.7% (n=40) (p=0.620). The overall postoperative
      complication rate was 5.1%. Postoperative complications developed in 7 patients
      (7.4%) in Group 1 and in 11 patients (4.3%) in Group 2 (p=0.250). CONCLUSIONS:
      Fluoroscopyfree retrograde intrarenal surgery seems to be a technically feasible
      and safe for the treatment of renal and proximal ureteral stone disease in
      uncomplicated selected cases.

PMID- 30230299
TI  - Medicolegal Review of Methotrexate Administration to Viable Intrauterine
      Pregnancies.
AB  - Objective: To examine 3 legal cases in which physicians prescribed methotrexate
      to women with a viable intrauterine pregnancy, presumed to be ectopic, resulting
      in adverse fetal outcomes. Study Design: We conducted an electronic literature
      search for legal cases using the keywords "methotrexate" and "pregnancy" in the
      LexisNexis legal research  engine as well as an Internet-wide search using the
      additional keyword "verdict." We manually searched the resultant list of
      identified cases and categorized the studies identified in the search by verdict,
      award amount, and outcome of the embryo exposed to methotrexate. Results: The
      monetary awards are typically greater when the embryo exposed to methotrexate
      lives and requires continuous medical and custodial care as compared to when the
      fetus dies in utero or shortly after birth. Conclusion: Physicians who, with all
      good intentions, prescribe methotrexate to women with a viable pregnancy,
      presumed to be ectopic, could find them-selves liable for an adverse fetal
      outcome. For the benefit of patients, their unborn offspring, and the liability
      exposure of the physician, it is important to be very cautious when prescribing
      methotrexate.

PMID- 30230300
TI  - Abnormal Uterine Bleeding Control by Sequential Application of Hysteroscopic
      Lesion Morcellation and Endometrial Ablation.
AB  - Objective: To assess the efficacy and safety of combined hysteroscopic
      morcellation/endometrial ablation for treating abnormal uterine bleeding (AUB).
      Study Design: Prospective case series from 5 U.S. gynecology clinics. Women with
      intrauterine polyps and/or type-0 myomas and transformed Uterine Fibroid Symptom
      and Health-Related Quality-of-Life (UFS-HRQoL) symptom severity score >=47 points
      (100 possible) underwent hysteroscopic morcellation (MyoSure) of intrauterine
      pathologies before endometrial radiofrequency ablation (NovaSure). Outcome
      measures were amenorrhea rate, UFS-HRQoL scoring, AUB retreatment/reintervention,
      bleeding days, and perioperative adverse events, through 12 months. Results: Of
      26 enrolled women, 24 were available through study completion. Lesions were 27%
      myomas and 73% polyps. Procedure room time was 19+/-13 minutes. Complete lesion
      eradication occurred in 96% of women. At 12 months, amenorrhea prevalence was 46%
      (p<0.0001 vs. baseline), and 87% of women reported either no bleeding or
      normalized bleeding. Bleeding/spotting days decreased from 15.7+/-7.4 to 3.1+/
      4.2 days/month (p<0.0001), symptom severity decreased from 75+/-13 to 12+/-18
      points (p<0.0001), and QoL scores increased from 29+/-18 to 88+/-23 points
      (p<0.0001). Three women required additional AUB intervention. Perioperative
      adverse events were minor nausea (n=1) and abdominopelvic cramping (n=2) without
      sequelae. Conclusion: Sequential hysteroscopic morcellation and endometrial
      radiofrequency ablation of intrauterine lesions in women with AUB increases
      amenorrhea rate, alleviates bleeding symptoms, and improves quality of life, with
      an acceptable safety profile.

PMID- 30230301
TI  - Young Women's Attitudes Towards Modern Reproductive Practices: A Survey Study
      Assessing What Young Women Want.
AB  - Objective: To assess young women's preferences and attitudes towards various
      options to create families at a time when women are increasingly postponing
      childbearing due to greater career focus and widespread availability of
      contraceptives. Study Design: Reported data were obtained from an electronic
      survey distributed over 6 months to approximately 7,000 females enrolled in
      American universities. Results: Most respondents ranked preferable childbearing
      modalities as follows: natural conception, assisted reproductive technologies,
      adoption, anonymous oocyte donation, and directed oocyte donation. The majority
      would consider using autologous oocyte cryopreservation for childbearing, but
      only a minority saw oocyte donation as a viable option. When queried about
      donating oocytes, 61% said they would donate to a sibling/friend, 51% to
      research, and 40% for clinical usage. Most would prefer to receive donation
      outcome information and would be comfortable being contacted by offspring. Most
      believed selecting recipient characteristics would increase their likelihood of
      donation, and 43% felt donors should receive additional compensation for
      desirable characteristics. Conclusion: Reproductive autonomy and fertility
      preservation are important to young educated females, a population sought-after
      for oocyte donation. Potential donors' desires for additional rights merit
      consideration as oocyte demand increases and frozen-oocyte banks emerge.

PMID- 30230302
TI  - A Novel Approach to Prenatal Measurement of the Fetal Frontal Lobe Using Three
      Dimensional Sonography.
AB  - Objective: To assess the feasibility of a standardized approach to biometric
      measurement of the fetal frontal lobe and to construct frontal lobe growth
      trajectories throughout gestation. Study Design: A sonographic 3-dimensional (3D)
      volume set was obtained and measured in 101 patients between 16.1 and 33.7
      gestational weeks. Measurements were obtained by 2 independent raters. To model
      the relationship between gestational age and each frontal lobe measurement,
      flexible linear regression models were fit using penalized regression splines.
      Results: The sample contained an ethnically diverse population (7.9% Native
      Americans, 45.5% Hispanics/Latinas). There was high interrater reliability
      (correlation coefficients 0.95, 1.0, and 0.87 for frontal lobe length, width, and
      height; p values <0.001). Graphs of the growth trajectories and corresponding
      percentiles were estimated as a function of gestational age. The estimated rates
      of frontal lobe growth were 0.096 cm/week, 0.247 cm/week, and 0.111 cm/week for
      length, width, and height, respectively. Conclusion: To our knowledge, this is
      the first study to examine fetal frontal lobe growth trajectories through 3D
      prenatal ultrasound examination. Such normative data will allow for future
      prenatal evaluation of a particular disease state by 3D ultrasound imaging.

PMID- 30230303
TI  - Cost-Benefit Analysis of Hysteroscopic Polypectomy Before Controlled Ovarian
      Hyperstimulation and Intrauterine Insemination in Infertile Women.
AB  - Objective: To examine the cost benefit of performing hysteroscopic polypectomy
      (HP) in infertile women with endometrial polyp(s) before controlled ovarian
      hyperstimulation with intrauterine insemination (COH/IUI). Study Design: Decision
      analytic model comparing costs and clinical outcomes. Results: HP and COH/IUI
      costs ranged from $537-$12,530 and $800-$7,600, respectively. Performing an HP
      before COH/IUI lowered fertility cost by $7,652 per clinical pregnancy. When
      COH/IUI costs remained constant, HP was most cost beneficial when the cost of HP
      was below a threshold value of $9,452. When HP costs remained constant, the
      threshold value at which HP was no longer cost beneficial was at COH/IUI costs
      below $704. The cost benefit was greatest when an office-based HP is performed.
      Conclusion: HP before COH/IUI is more cost beneficial than fertility treatment
      alone, particularly when office-based hysteroscopy is performed.

PMID- 30230304
TI  - A Simple Method for Excluding Uterine Canalization Defects Using Two-Dimensional
      Ultrasound in Infertile Women.
AB  - Objective: To compare the uterine transverse diameter (UTD) in women with normal
      uteri and women with uterine canalization defects as well as to assess its
      performance for ruling out such defects. Study Design: Retrospective analysis of
      prospectively collected data in a series of selected women with primary or
      secondary infertility. Measurement of UTD and 3D volume acquisition for
      subsequent off-line analysis was performed in order to identify possible
      canalization defects. UTD of the normal uterus, measured by 2D ultrasound, was
      compared to that of arcuate, subseptate, and septate uteri. ROC curve was plotted
      to determine the best UTD cutoff for differentiating normal from abnormal uteri.
      Results: A total of 421 women were ultimately evaluated. UTD was significantly
      larger in women with arcuate (53.3 mm, SD 6.3, p<0.05), subseptate (55.0 mm, SD
      6.7, p<0.05), and septate (56.0 mm, SD 4.8, p<0.05) uterus as compared with the
      normal uterus (45.9 mm, SD 7.1). ROC curve showed that the best UTD cutoff for
      ruling out the presence of a uterine canalization defect was 45 mm (AUC 0.809,
      95% CI 0.768-0.849). Conclusion: Measurement of UTD may be a simple and practical
      method for ruling out a uterine canalization defect in infertile women.

PMID- 30230305
TI  - Effects of Estradiol at Different Levels on Rabbit Endometrial Repair After
      Curettage.
AB  - Objective: To evaluate the effects of estradiol on endometrial regeneration and
      stromal fibrosis after endometrial curettage. Study Design: This is an
      experimental, prospective study. Combining ovariectomized rabbits and different
      doses of estrogen replacement, we divided 33 female rabbits into 4 groups:
      control, low estrogen, moderate estrogen, and high estrogen. Hematoxylin-eosin
      staining and Masson's trichrome staining were used to assess the regeneration of
      endometrial glands and the degree of stromal fibrosis. Results: Before curettage,
      estradiol at high serum level could stimulate endometrial gland regeneration as
      assessed by the number of endometrial glands in paraffin sections stained with
      hematoxylin and eosin. However, after curettage, both high and low doses of
      estradiol impaired glandular regeneration while enhancing stro-ma fibrosis, which
      was calculated as the ratio of stromal fibrosis area to endometrial area in
      paraffin sections stained with Masson's trichrome, as compared with the control
      group. In addition, estradiol is favorable to endometrial repair at the
      physiological level. Conclusion: Estradiol compromises glandular regeneration and
      promotes stromal fibrosis at both low and high serum levels but is favorable to
      endometrial repair at the physiological level. This study may provide new insight
      for the role of estrogen therapy after hysteroscopic division of intrauterine
      adhesion.

PMID- 30230306
TI  - Primary Gestational Trophoblastic Disease of the Fallopian Tube: A Case Series
      Analysis and Literature Review.
AB  - Objective: To review the clinicopathological characteristics, diagnosis, and
      treatment of tubal gestational trophoblastic disease (GTD) misdiagnosed as tubal
      pregnancy. Study Design: From January 1, 2004, to December 31, 2013, a total of
      619 patients with GTD were recorded at the Obstetrics and Gynecology Hospital of
      Fudan University. Among them, 4 cases of tubal GTD were initially misdiagnosed as
      tubal pregnancies. We retrospectively analyzed the clinicopathologic
      characteristics, diagnosis, treatment, and prognosis of those 4 patients.
      Results: All 4 patients showed symptoms similar to those of tubal pregnancy. The
      serum human chorionic gonadotropin (beta-hCG) level at presentation was elevated
      >50,000 mIU/mL. All cases were treated by laparoscopic surgery. Misdiagnosis of
      the 3 cases of complete hydatidiform mole (CHM) and 1 choriocarcinoma were
      identified by postoperational histopathology. At 7 days postoperation the beta
      hCG level decreased to 304-6,115 mIU/mL. One case of tubal CHM received a second
      operation, and 3 cases received chemotherapy due to the unsatisfactory decrease
      in beta-hCG level. The patient with choriocarcinoma received routine adjuvant
      chemotherapy. All of the patients achieved complete remission, and none relapsed
      for a median of 20 months' follow-up. Conclusion: Tubal GTD is rare and is often
      misdiagnosed for tubal pregnancy. Salpingectomy, intraoperative frozen section,
      and close follow-up were recommended, and prophylactic chemotherapy was
      unnecessary.

PMID- 30230307
TI  - Severity of Diminished Ovarian Reserve and Chance of Success with Assisted
      Reproductive Technology.
AB  - Objective: To describe the relationship between severe diminished ovarian reserve
      (DOR) and assisted reproductive technology outcomes. Study Design: Retrospective
      cohort including all United States' fertility centers reporting to the CDC
      National ART Surveillance System, 2004-2012. Among women aged <41 (504,266 fresh
      autologous IVF cycles), we calculated cancellation rate/cycle and pregnancy
      rate/transfer, stratified by age, by maximum follicle-stimulating hormone (FSH).
      Cancellation rate per cycle and pregnancy, live birth, and miscarriage rates per
      transfer were compared among women with and without DOR. We used multivariable
      log binomial regression, stratified by age, to calculate adjusted relative risk
      (aRR) for the association between DOR and these outcomes and, within DOR groups,
      between stimulation type and outcomes. Results: Cancellation rate/cycle increased
      with increasing FSH and with DOR severity. For women aged <35 who underwent
      transfer, aRR for pregnancy and live birth indicated slightly reduced likelihood
      of these outcomes (severe vs. no DOR); confidence intervals approached the null.
      Among women with severe DOR, stimulation type was not associated with likelihood
      of pregnancy or live birth per transfer in any group except women ages 38-40.
      Conclusion: Women with severe DOR are at significantly increased risk of
      cancellation; however, those who undergo transfer have pregnancy and live birth
      chances similar to those of women without DOR after controlling for cycle
      characteristics.

PMID- 30230308
TI  - Contact Resistance in Ambipolar Organic Field-Effect Transistors Measured by
      Confocal Photoluminescence Electro-Modulation Microscopy.
AB  - Although it is theoretically expected that all organic semiconductors support
      ambipolar charge transport, most organic transistors either transport holes or
      electrons effectively. Single-layer ambipolar organic field-effect transistors
      enable the investigation of different mechanisms in hole and electron transport
      in a single device since the device architecture provides a controllable planar
      pn-junction within the transistor channel. However, a direct comparison of the
      injection barriers and of the channel conductivities between electrons and holes
      within the same device cannot be measured by standard electrical
      characterization. This article introduces a novel approach for determining
      threshold gate voltages for the onset of the ambipolar regime from the position
      of the pn-junction observed by photoluminescence electro-modulation (PLEM)
      microscopy. Indeed, the threshold gate voltage in the ambipolar bias regime
      considers a vanishing channel length, thus correlating the contact resistance.
      PLEM microscopy is a valuable tool to directly compare the contact and channel
      resistances for both carrier types in the same device. The reported results
      demonstrate that designing the metal/organic-semiconductor interfaces by aligning
      the bulk metal Fermi levels to the highest occupied molecular orbital or lowest
      unoccupied molecular orbital levels of the organic semiconductors is a too
      simplistic approach for optimizing the charge-injection process in organic field
      effect devices.

PMID- 30230309
TI  - Paving the Way for K-Ion Batteries: Role of Electrolyte Reactivity through the
      Example of Sb-Based Electrodes.
AB  - Developing potassium-ion batteries remains a challenge so far due to the lack of
      efficient electrolytes. Moreover, the high reactivity of K metal and the use of
      half-cells may greatly alter both the electrochemical performance and the solid
      electrolyte interphase formation. Here, it is shown that in K metal/Sb half
      cells, Coulombic efficiency improvement is achieved by the addition of
      fluoroethylene carbonate + vinylene carbonate to propylene carbonate (PC), the
      replacement of PC by ethylene carbonate/diethyl carbonate, and the replacement of
      KPF6 by potassium bis(fluorosulfonyl)imide. Surprisingly, however, storage of
      cells containing K metal leads to the coloration of K metal, separators, and Sb
      electrodes, whereas no change occurs for cells prepared without K metal. These
      results demonstrate that for all electrolytes, the high electrolyte reactivity
      with K metal also influences the Sb/electrolyte interface via a cross-talk
      mechanism. This observation is supported by gas chromatography/mass spectrometry
      analysis of electrolytes and X-ray photoelectron spectroscopy analysis of Sb
      electrodes. In summary, these results indicate that the search for efficient
      electrolytes for potassium-ion batteries must be carried out in full cells if one
      wants to obtain meaningful correlations between electrochemical performance and
      electrode/electrolyte interfacial properties. Overall, the results presented here
      are also likely to benefit the development of other emerging Na- and Mg-ion cell
      chemistries.

PMID- 30230310
TI  - Random Mutagenesis Analysis of the Influenza A M2 Proton Channel Reveals Novel
      Resistance Mutants.
AB  - The influenza M2 proton channel is a major drug target, but unfortunately, the
      acquisition of resistance mutations greatly reduces the functional life span of a
      drug in influenza treatment. New M2 inhibitors that inhibit mutant M2 channels
      otherwise resistant to the early adamantine-based drugs have been reported, but
      it remains unclear whether and how easy resistance could arise to such
      inhibitors. We have combined a newly developed proton conduction assay with an
      established method for selection and screening, both Escherichia coli-based, to
      enable the study of M2 function and inhibition. Combining this platform with two
      groups of structurally different M2 inhibitors allowed us to isolate drug
      resistant M2 channels from a mutant library. Two groups of M2 variants emerged
      from this analysis. A first group appeared almost unaffected by the inhibitor,
      M_089 (N13I, I35L, and F47L) and M_272 (G16C and D44H), and the single
      substitution variants derived from these (I35L, L43P, D44H, and L46P).
      Functionally, these resemble the known drug resistant M2 channels V27A, S31N, and
      swine flu. In addition, a second group of tested M2 variants were all still
      inhibited by drugs but to a lesser extent than wild type M2. Molecular dynamics
      simulations aided in distinguishing the two groups where drug binding to the wild
      type and the less resistant M2 group showed a stable positioning of the ligand in
      the canonical binding pose, as opposed to the drug resistant group in which the
      ligand rapidly dissociated from the complex during the simulations.

PMID- 30230312
TI  - A Robust Proton Flux (pHlux) Assay for Studying the Function and Inhibition of
      the Influenza A M2 Proton Channel.
AB  - The M2 protein is an important target for drugs in the fight against the
      influenza virus. Because of the emergence of resistance against antivirals
      directed toward the M2 proton channel, the search for new drugs against resistant
      M2 variants is of high importance. Robust and sensitive assays for testing
      potential drug compounds on different M2 variants are valuable tools in this
      search for new inhibitors. In this work, we describe a fluorescence sensor-based
      assay, which we termed "pHlux", that measures proton conduction through M2 when
      synthesized from an expression vector in Escherichia coli. The assay was compared
      to a previously established bacterial potassium ion transport complementation
      assay, and the results were compared to simulations obtained from analysis of a
      computational model of M2 and its interaction with inhibitor molecules. The
      inhibition of M2 was measured for five different inhibitors, including
      Rimantadine, Amantadine, and spiro type compounds, and the drug resistance of the
      M2 mutant variants (swine flu, V27A, and S31N) was confirmed. We demonstrate that
      the pHlux assay is robust and highly sensitive and shows potential for high
      throughput screening.

PMID- 30230311
TI  - Maintenance DNA Methyltransferase Activity in the Presence of Oxidized Forms of 5
      Methylcytosine: Structural Basis for Ten Eleven Translocation-Mediated DNA
      Demethylation.
AB  - A precise balance of DNA methylation and demethylation is required for epigenetic
      control of cell identity, development, and growth. DNA methylation marks are
      introduced by de novo DNA methyltransferases DNMT3a/b and are maintained
      throughout cell divisions by DNA methyltransferase 1 (DNMT1), which adds methyl
      groups to hemimethylated CpG dinucleotides generated during DNA replication. Ten
      eleven translocation (TET) dioxygenases oxidize 5-methylcytosine (mC) to 5
      hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxylcytosine (caC),
      a process known to induce DNA demethylation and gene reactivation. In this study,
      we investigated the catalytic activity of human DNMT1 in the presence of oxidized
      forms of mC. A mass spectrometry-based assay was employed to study the kinetics
      of DNMT1-mediated cytosine methylation in CG dinucleotides containing C, mC, hmC,
      fC, or caC across from the target cytosine. Homology modeling, coupled with
      molecular dynamics simulations, was used to explore the structural consequences
      of mC oxidation with regard to the geometry of protein-DNA complexes. The DNMT1
      enzymatic activity was strongly affected by the oxidation status of mC, with the
      catalytic efficiency decreasing in the following order: mC > hmC > fC > caC.
      Molecular dynamics simulations revealed that DNMT1 forms an unproductive complex
      with DNA duplexes containing oxidized forms of mC as a consequence of altered
      interactions of the target recognition domain of the protein with the C-5
      substituent on cytosine. Our results provide new structural and mechanistic
      insight into TET-mediated DNA demethylation.

PMID- 30230313
TI  - Ligand Impact on Monolayer Electrochromic Material Properties.
AB  - In this study, we present a range of efficient highly durable electrochromic
      materials that demonstrate excellent redox and lifetime stability, sufficient
      coloration contrast ratios, and the best-in-class electron-transfer constants.
      The materials were formed by anchoring as little as a monolayer of predefined
      iron complexes on a surface-enhanced conductive solid support. The thickness of
      the substrate was optimized to maximize the change in optical density. We
      demonstrate that even a slight change in molecular sterics and electronics
      results in materials with sufficiently different properties. Thus, minor changes
      in the ligand design give access to materials with a wide range of color
      variations, including green, purple, and brown. Moreover, ligand architecture
      dictates either orthogonal or parallel alignment of corresponding metal complexes
      on the surface due to mono- or bis-quaternization. We demonstrate that
      monoquaternization of the complexes during anchoring to the surface-bound
      template layer results in redshifts of the photoabsorption peak. The results of
      in-solution bis-methylation supported by density functional theory calculations
      show that the second quaternization may lead to an opposite blueshift (in
      comparison with monomethylated analogs), depending on the ligand electronics and
      the environmental change. It is shown that the variations of the photoabsorption
      peak position for different ligands upon attachment to the surface can be related
      to the calculated charge distribution and excitation-induced redistribution.
      Overall, the work demonstrates a well-defined method of electrochromic material
      color tuning via manipulation of sterics and electronics of terpyridine-based
      ligands.

PMID- 30230314
TI  - Essential Role of Spinel ZnFe2O4 Surfaces during Lithiation.
AB  - Spinel zinc ferrite (ZnFe2O4) is a well-known anode material in lithium ion
      batteries (LIBs) because of its large theoretical capacity. However, the high
      potentials observed at the initial stage of lithiation cannot be captured using a
      model of Li+ intercalation into the stoichiometric ZnFe2O4 bulk. Here, using
      density functional theory, we report for the first time that the ZnFe2O4 surfaces
      are responsible for the measured initial potentials. Among the three identified
      stable surfaces, ZnFeO2-terminated ZnFe2O4(1 1 0), O-terminated ZnFe2O4(1 1 1),
      and Zn-terminated ZnFe2O4(1 1 1), both (1 1 1) surfaces display higher lithiation
      potentials than the (1 1 0) surface, and the estimated potentials based on Zn
      terminated (1 1 1) fit well with the experimental observations, whereas using the
      models based on ZnFe2O4(1 1 0) and previously ZnFe2O4 bulk, the estimated
      potentials are much lower. In terms of Li+ diffusion, the Zn-terminated ZnFe2O4(1
      1 1) surface is the most active, where the energetically favorable saturation of
      Li+ on the surface is able to facilitate the process. Our results provide a new
      strategy for the design of LIB materials, via controlling the particle shape and
      the associated surface characteristics, thus enhancing the discharging
      performance.

PMID- 30230315
TI  - Multifunctional Epoxy-Based Solid Polymer Electrolytes for Solid-State
      Supercapacitors.
AB  - Solid polymer electrolytes (SPEs) have drawn attention for promising
      multifunctional electrolytes requiring very good mechanical properties and ionic
      conductivity. To develop a safe SPE for energy storage applications, mechanically
      robust cross-linked epoxy matrix is combined with fast ion-diffusing ionic
      liquid/lithium salt electrolyte (ILE) via a simple one-pot curing process. The
      epoxy-rich SPEs show higher Young's modulus ( E), with higher glass transition
      temperature ( Tg) but lower ionic conductivity (sigmadc) with a higher activation
      energy, compared to the ILE-rich SPEs. The incorporation of inorganic robust
      Al2O3 nanowire simultaneously provides excellent mechanical robustness ( E ~ 1
      GPa at 25  degrees C) and good conductivity (sigmadc ~ 2.9 * 10-4 S/cm at 25 
      degrees C) to the SPE. This suggests that the SPE has a bicontinuous microphase
      separation into ILE-rich and epoxy-rich microdomain, where ILE continuous
      conducting phases are intertwined with a sturdy cross-linked amorphous epoxy
      framework, supported by the observation of the two Tgs and low tortuosity as well
      as the microstructural investigation. After assembling the SPE with activated
      carbon electrodes, we successfully demonstrate the supercapacitor performance,
      exhibiting high energy and power density (75 W h/kg at 382 W/kg and 9.3 kW/kg at
      44 W h/kg). This facile strategy holds tremendous potential to advance
      multifunctional energy storage technology for next-generation electric vehicles.

PMID- 30230316
TI  - Robust and High Spatial Resolution Light Addressable Electrochemistry Using
      Hematite (alpha-Fe2O3) Photoanodes.
AB  - Light addressable/activated electrochemistry (LAE) has recently attracted
      attention as it can provide spatially resolved electrochemical information
      without using pre-patterned electrodes whose sizes and positions are
      unchangeable. Here, we propose hematite (alpha-Fe2O3) as the photoanode for LAE,
      which does not require any sort of surface modification for protection or
      facilitating charge transfer. As experimentally confirmed with various redox
      species, hematite is stable enough to be used for repetitive electroanalytical
      measurements. More importantly, it offers exceptionally high spatial resolution
      so that the "virtual electrode" is exactly as large as the light spot owing to
      the short diffusion length of the minority carriers. Quantitative analysis of
      dopamine in this study shows that the hematite-based photoanode is a promising
      platform for many potential LAE applications including spatially selective
      detection of oxidizable biomolecules.

PMID- 30230317
TI  - Polymer-Based Nanomaterials for Photothermal Therapy: From Light-Responsive to
      Multifunctional Nanoplatforms for Synergistically Combined Technologies.
AB  - Materials for the treatment of cancer have been studied comprehensively over the
      past few decades. Among the various kinds of biomaterials, polymer-based
      nanomaterials represent one of the most interesting research directions in
      nanomedicine because their controlled synthesis and tailored designs make it
      possible to obtain nanostructures with biomimetic features and outstanding
      biocompatibility. Understanding the chemical and physical mechanisms behind the
      cascading stimuli-responsiveness of smart polymers is fundamental for the design
      of multifunctional nanomaterials to be used as photothermal agents for targeted
      polytherapy. In this review, we offer an in-depth overview of the recent advances
      in polymer nanomaterials for photothermal therapy, describing the features of
      three different types of polymer-based nanomaterials. In each case, we
      systematically show the relevant benefits, highlighting the strategies for
      developing light-controlled multifunctional nanoplatforms that are responsive in
      a cascade manner and addressing the open issues by means of an inclusive state-of
      the-art review. Moreover, we face further challenges and provide new perspectives
      for future strategies for developing novel polymeric nanomaterials for
      photothermally assisted therapies.

PMID- 30230318
TI  - Comparative Pharmacokinetics of High and Low Doses of the Herbicide Propanil in
      Mice.
AB  - We have documented that the herbicide propanil is immunotoxic in mice, and our in
      vitro tissue culture experiments largely recapitulate the in vivo studies.
      Laboratory studies on environmental contaminants are the most meaningful when
      these studies are conducted using concentrations that approximate levels in the
      environment. Many techniques to measure the distribution and pharmacokinetics
      (PK) on compounds rely on techniques, such as liquid scintillation counting (LSC)
      of radio-labeled starting compound, that require concentrations higher than
      environmental levels. The aim of this study was to compare tissue PK after
      exposure to propanil concentrations more relevant to levels of exposure to
      agricultural workers and the general population to concentrations previously
      reported for laboratory studies. To this end, we conducted a study to measure
      propanil distribution in three immune organs, using ultrasensitive accelerator
      mass spectrometry (AMS). We used two doses: the lower dose modeled levels
      expected in the environment or long-term occupational exposure to low doses,
      while the higher dose was to model the effects of an accidental exposure. Our
      results showed that the distribution and PK profiles from these two different
      concentrations was markedly different. The profile of the high dose
      (concentration) exposure was indicative of saturation of the detoxifying
      capability of the animal. In contrast, at the lower environmentally relevant
      concentration, in vivo concentrations of propanil in spleen, liver, and blood
      dropped to a very low level by 720 min. In conclusion, these studies highlight
      the differences in PK of propanil at these two doses, which suggests that the
      toxicity of this chemical should be re-investigated to obtain better data on
      toxic effects at doses relevant for humans.

PMID- 30230319
TI  - Mussel-Inspired and Magnetic Co-functionalization of Hexagonal Boron Nitride in
      Poly(vinylidene fluoride) Composites Toward Enhanced Thermal and Mechanical
      Performance for Heat Exchangers.
AB  - Thermal-conductive polymer composites have developed to be a hotspot in academic
      and industrial fields recently. Both efficient heat transport and superior
      mechanical properties are of critical significance for high-performance thermal
      conductive devices. In this paper, magnetic hexagonal boron nitride (mhBN) with
      excellent interfacial compatibility is successfully synthesized by dopamine and
      magnetic co-functionalization, and mhBN-poly(vinylidene fluoride) (mhBN-PVDF)
      composites with a combination of high thermal conductivity and outstanding
      mechanical property are achieved due to the integration of excellent interfacial
      interaction and aligned filler architecture into one material's system. The
      thermal conductivity increases from 0.35 W/(m K) for the 20 wt % pure BN-PVDF to
      0.82 W/(m K) after the dopamine modification and further to 1.43 W/(m K) after
      alignment. The effective medium approximation model demonstrates that the
      optimization of mhBN orientation and decrease of thermal resistance are two major
      factors for the enhancement of thermal conductivity. Moreover, the mhBN-PVDF
      composites also exhibit excellent tensile strength (168.5 MPa at 15 wt % content)
      and impact strength (20-30 kJ/m2). The significantly enhanced thermal and
      mechanical properties result in the excellent heat exchange ability and
      durability in the heat exchange test, which is important for potential
      application in the heat exchange industry.

PMID- 30230320
TI  - Distinct Differences in Structural States of Conserved Histidines in Two Related
      Proteins: NMR Studies of the Chemokines CXCL1 and CXCL8 in the Free Form and
      Macromolecular Complexes.
AB  - Hydrogen-bonding and ionic interactions play fundamental roles in macromolecular
      recognition and function. In contrast to lysines and arginines, how histidines
      mediate these interactions is less well-understood due to the unique properties
      of its side chain imidazole that include an aromatic ring with two titratable
      nitrogens, a p Ka that can vary significantly, and the ability to exist in three
      distinct forms: protonated imidazolium and two tautomeric neutral (Ndelta1 and
      Nepsilon2) states. Here, we characterized the structural features of histidines
      in the chemokines CXCL8 and CXCL1 in the free, GAG heparin-bound, and CXCR2
      receptor N-terminal domain-bound states using solution NMR spectroscopy. CXCL8
      and CXCL1 share two conserved histidines, one in the N-loop and the other in the
      30s loop. In CXCL8, both histidines exist in the Nepsilon2 tautomeric state in
      the free, GAG-bound, and receptor-bound forms. On the other hand, in unliganded
      CXCL1, each of the two histidines exists in two states, as the neutral Nepsilon2
      tautomer and charged imidazolium. Further, both histidines exclusively exist as
      the imidazolium in the GAG-bound and as the Nepsilon2 tautomer in the receptor
      bound forms. The N-loop histidine alone in both chemokines is involved in direct
      GAG and receptor interactions, indicating the role of the 30s loop varies between
      the chemokines. Our observation that the structural features of conserved
      histidines and their functional role in two related proteins can be quite
      different is novel. We further propose that directly probing the imidazole
      structural features is essential to fully appreciate the molecular basis of
      histidine function.

PMID- 30230321
TI  - Identification of the Novel Capecitabine Metabolites in Capecitabine-Treated
      Patients with Hand-Foot Syndrome.
AB  - Hand-foot syndrome (HFS), the most common side effect of capecitabine, is a dose
      limiting cutaneous toxicity with only rare therapeutic options. The causative
      mechanisms of HFS are still unclear. Many studies suggested that capecitabine or
      its metabolites caused the toxicity. This study is attempting to determine if
      there are any new metabolites that may be present and be linked to toxicity. For
      this purpose, 25 patients who ingested capecitabine orally were enrolled and
      divided into HFS positive and negative groups. Urine and plasma samples were
      collected before administration and five cycles after administration. Eleven
      phase I and phase II metabolites of capecitabine were detected and identified by
      ultraperformance liquid chromatography coupled with quadrupole time-of-flight
      tandem mass spectrometry with a metabolomic approach and MetaboLynxXS. Nine novel
      metabolites of capecitabine were identified herein, which were not observed in
      the HFS negative group. Their structures were confirmed by chemical synthesis and
      nuclear magnetic resonance spectroscopy. The cytotoxities of capecitabine and its
      metabolites on HaCaT cells were measured. Among them, M9/10 exhibited significant
      inhibitory activity, and they were produced via acetylation mainly by N
      acetyltransferase 2. Our study comprehensively described the metabolism of
      capecitabine in patients with HFS and detected the novel pathways of
      capecitabine, which was a positive significance for the mechanism of HFS.

PMID- 30230322
TI  - Formation of Aluminum Hydroxide-Doped Surface Passivating Layers on Pyrite for
      Acid Rock Drainage Control.
AB  - The aim of this study was to test the performance of a novel method for acid rock
      drainage (ARD) control through the formation of Al(OH)3-doped passivating surface
      layers on pyrite. At pH 2.0 and 4.0, there was no obvious inhibition of the
      pyrite oxidation rate on addition of 20 mg L-1 Al3+ (added as AlCl3.6H2O). In
      comparison, the pyrite oxidation rate at circumneutral pH (7.4 +/- 0.4) decreased
      with increasing added Al3+ with ~98% reduction in long-term (282 days)
      dissolution rates in the presence of 20 mg L-1 Al3+. Al3+ was added to the
      solution and allowed to equilibrate prior to pyrite addition (2 g L-1).
      Consequently almost all Al3+ (>99.9%) was initially present as aluminum hydroxide
      precipitates at pH 7.4. X-ray photoelectron spectroscopy analysis showed a
      significant concentration of Al3+ (20.3 at. %) on the pyrite surface reacted at
      pH 7.4 with 20 mg L-1 added Al3+, but no Al3+ on pyrite surfaces reacted at pH
      2.0 and 4.0 with added Al3+. Transmission electron microscopy and synchrotron X
      ray absorption near edge spectroscopy analyses indicated that compact surface
      layers containing both goethite and amorphous or nanocrystalline Al(OH)3 formed
      in the presence of 20 mg L-1 Al3+ at circumneutral pH, in contrast to the porous
      goethite surface layers formed on pyrite dissolved in the absence of Al3+ under
      otherwise identical conditions. This work demonstrates the potential for novel Al
      based pyrite passivation of relevance to the mining industry where suitable Al
      rich waste materials are available for ARD control interventions.

PMID- 30230323
TI  - Influence of Structural (Cation and Anion) Order in the Superconducting
      Properties of Ozone-Oxidized Mo0.3Cu0.7Sr2RECu2O y (RE = Yb, Tm, Gd, Nd, and Pr).
AB  - The influence of rare earth (RE) elements on superconducting properties of the
      transition element (TE)-substituted TE xCu1- xSr2RECu2O y cuprates has not been
      sufficiently emphasized so far. In the case of molibdo-cuprates with the general
      formula Mo0.3Cu0.3Sr2RECu2O y, all the RE element containing compounds except La,
      Ce, and Lu can be prepared at room pressure. The influence of the crystal
      structure on the superconducting properties after ozone oxidation of the present
      system is reported selecting three groups of RE elements attending to their
      different atom sizes: small (Yb and Tm), medium (Gd), and big (Nd and Pr).
      Advanced transmission electron microscopy, various diffraction techniques, and
      spectroscopic analysis have been used to demonstrate that the increase of
      structural disorder complemented with a decrease in the hole content play a major
      role in the vanishing of superconductivity within the present system.

PMID- 30230324
TI  - Hemiporphyrazine-Involved Sandwich Dysprosium Double-Decker Single-Ion Magnets.
AB  - Both heteroleptic (phthalocyaninato)(hemiporphyrazinato) and homoleptic
      bis(hemiporphyrazinato) dysprosium double-decker complexes, Dy[H(Hp)2] (1) and
      Dy[H(Pc)(Hp)] (2) (H2Pc = metal-free phthalocyanine; H2Hp = metal-free
      hemiporphyrazine), were designed, synthesized, and structurally characterized.
      The dysprosium center in both double-deckers are octa-coordinated with a nearly
      ideal square-antiprismatic coordination geometry, which provides an increased
      molecular anisotropy for the dysprosium ion and ensures the strengthened magnetic
      properties of both single-ion magnets (SIMs) in terms of coordination geometry.
      Magnetic studies reveal that both double-deckers exhibit typical SIM behavior
      with a spin reversal energy barrier of 80.1 +/- 6.3 K for 1 and 57.3 +/- 3.8 K
      for 2 as well as the hysteresis loops emerging at 3 K. In particular,
      introduction of two Hp ligands with four pyridine nitrogen atoms coordinated with
      the dysprosium spin center endows Dy[H(Hp)2] (1) with the thus far highest energy
      barrier among the sandwich-type dysprosium SIMs with N4-macrocyclic ligands,
      revealing the potential applications of sandwich-type lanthanide complexes with
      Hp ligands in molecular-based information storage.

PMID- 30230325
TI  - Thionoesters: A Native Chemical Ligation-Inspired Approach to Cysteine-Triggered
      H2S Donors.
AB  - Native chemical ligation (NCL) is a simple, widely used, and powerful synthetic
      tool to ligate N-terminal cysteine residues and C-terminal alpha-thioesters via a
      thermodynamically stable amide bond. Building on this well-established
      reactivity, as well as advancing our interests in the chemical biology of
      reactive sulfur species including hydrogen sulfide (H2S), we hypothesized that
      thionoesters, which are constitutional isomers of thioesters, would undergo a
      similar NCL reaction in the presence of cysteine to release H2S under
      physiological conditions. Herein, we report mechanistic and kinetic
      investigations into cysteine-mediated H2S release from thionoesters. We found
      that this reaction proceeds with high H2S-releasing efficiency (~80%) and with a
      rate constant (9.1 +/- 0.3 M-1 s-1) comparable to that for copper-catalyzed azide
      alkyne cycloadditions (CuAAC). Additionally, we found that the final product of
      the reaction of cysteine with thionoesters results in the formation of a stable
      dihydrothiazole, which is an iron-binding motif commonly found in siderophores
      produced by bacteria during periods of nutrient deprivation.

PMID- 30230326
TI  - Copper-Catalyzed N-Formylation of Amines through Tandem
      Amination/Hydrolysis/Decarboxylation Reaction of Ethyl Bromodifluoroacetate.
AB  - Ethyl bromodifluoroacetate (BrCF2COOEt) was first used as the N-formylating
      reagent in the copper-catalyzed N-formylation of amines. A range of primary,
      secondary, cyclic arylamines, and aliphatic amines underwent the N-formylation
      smoothly to furnish the N-formamides in moderate-to-excellent yields.

PMID- 30230327
TI  - Biotransformation of Artemisinin to 14-Hydroxydeoxyartemisinin: C-14
      Hydroxylation by Aspergillus flavus.
AB  - The biotransformation of the front-line antimalarial drug, artemisinin (1) by the
      filamentous fungus Aspergillus flavus MTCC-9167 was investigated. Incubation of
      compound 1 with A. flavus afforded a new hydroxy derivative (2) along with three
      known metabolites (3-5). The new compound was characterized as 14
      hydroxydeoxyartemisinin (2) by extensive spectroscopic data analysis (IR, 1H and
      13C NMR, HSQC, HMBC, COSY, NOESY, and HR-ESIMS). The known metabolites were
      identified as deoxyartemisinin (3), artemisinin G (4), and 4alpha
      hydroxydeoxyartemisinin (5). This is the first report of hydroxylation of a
      secondary methyl of artemisinin at C-14 by the fungus A. flavus, which is
      synthetically not accessible. In addition, these compounds were evaluated for
      their in vitro antiplasmodial activity. Artemisinin G (4) exhibited IC50 values
      in the submicromolar range, which was better than those of the nonperoxidic
      metabolites.

PMID- 30230328
TI  - Construction of Fully Substituted 2-Pyridone Derivatives via Four-Component
      Branched Domino Reaction Utilizing Microwave Irradiation.
AB  - Microwave irradiation, four-component branched domino reaction of methyl
      acetoacetate/2,4-pentanedione, diethyl malonate, triethyl orthoformate and amines
      offering an extremely efficient strategy for the construction of fully
      substituted 2-pyridone derivatives under sustainable conditions is established.
      This self-sorting branched domino transformation is proposed to proceed separate
      through N-nucleophilic addition and imine-enamine tautomerization/condensation
      reaction generated from enamino ester and diethyl ethoxymethylenemalonate, and
      then would be subjected to an aza-ene reaction and intramolecular cyclization
      mechanism to afford the 2-pyridones with only water and ethanol as byproducts.
      The simple experimental procedure, high bond-forming efficiency, step and atom
      economy, inexpensive readily available starting materials, moderate to excellent
      yields, and good functional group compatibility are other noteworthy advantages
      of this method.

PMID- 30230329
TI  - Discrete and Stereospecific Oligomers Prepared by Sequential and Alternating
      Single Unit Monomer Insertion.
AB  - Natural biopolymers, such as DNA and proteins, have uniform microstructures with
      defined molecular weight, precise monomer sequence, and stereoregularity along
      the polymer main chain that affords them unique biological functions. To
      reproduce such structurally perfect polymers and understand the mechanism of
      specific functions through chemical approaches, researchers have proposed using
      synthetic polymers as an alternative due to their broad chemical diversity and
      relatively simple manipulation. Herein, we report a new methodology to prepare
      sequence-controlled and stereospecific oligomers using alternating radical chain
      growth and sequential photoinduced RAFT single unit monomer insertion (photo-RAFT
      SUMI). Two families of cyclic monomers, the indenes and the N-substituted
      maleimides, can be alternatively inserted into RAFT agents, one unit at a time,
      allowing the monomer sequence to be controlled through sequential and alternating
      monomer addition. Importantly, the stereochemistry of cyclic monomer insertion
      into the RAFT agents is found to be trans-selective along the main chains due to
      steric hindrance from the repeating monomer units. All investigated cyclic
      monomers provide such trans-selectivity, but analogous acyclic monomers give a
      mixed cis- and trans-insertion.

PMID- 30230330
TI  - High Volumetric Hydrogen Adsorption in a Porous Anthracene-Decorated Metal
      Organic Framework.
AB  - We report an unprecedented ligand-based binding domain for D2 within a porous
      metal-organic framework (MOF) material as confirmed by neutron powder diffraction
      studies of D2-loaded MFM-132a. A tight pocket of 6 A diameter is formed by the
      close packing of three anthracene panels, and it is here rather than the open
      metal sites where D2 binds preferentially. As a result, MFM-132a shows
      exceptional volumetric hydrogen adsorption (52 g L-1 at 60 bar and 77 K) and the
      highest density of adsorbed H2 within its pores among all the porous materials
      reported to date under the same conditions. This work points to a new direction
      for H2 storage in porous materials using polyaromatic ligand-based sites.

PMID- 30230331
TI  - Ligand Isomerism in Coordination Cages.
AB  - Complexation reactions of palladium(II) nitrate with a set of 3-pyridyl appended
      nonchelating bidentate ligands possessing regioisomeric phenylene-diurea
      functionalities as spacers were carried out. The ligands utilized in this study
      are 1,1'-(1,2-phenylene)bis(3-(pyridin-3-yl)urea), L1; 1,1'-(1,3-phenylene)bis(3
      (pyridin-3-yl)urea), L2; and 1,1'-(1,4-phenylene)bis(3-(pyridin-3-yl)urea), L3.
      The complexation reactions of the ligands (L1, L2, and L3) with palladium(II)
      produced single discrete isomeric cages (1, 2, and 3) of Pd2L4 formulation in
      each case and thereby illustrated ligand-isomerism in coordination cages. All 16
      hydrogen atoms of eight urea moieties present in four ligand strands are
      delineated completely endohedrally in cage 1 and completely exohedrally in cage
      3, whereas cage 2 exhibited half of the urea hydrogens in exohedral locations and
      the remaining half in endohedral locations. In addition to the variable number of
      solvent molecules, the cavities of cages 1 and 2 lodged four and two nitrate
      ions, respectively, using the endohedral (H)urea atoms (i.e., NH groups) as
      binding sites, whereas the cavity of 3 remained anion free. The abilities of the
      complexes 1-3 for adsorption of CO2 gas are demonstrated, and their behaviors are
      compared.

PMID- 30230332
TI  - Addition to "Reactions of Chemically Activated Formic Acid Formed via HCO + OH".

PMID- 30230333
TI  - Primed for Efficient Motion: Ultrafast Excited State Dynamics and Optical
      Manipulation of a Four Stage Rotary Molecular Motor.
AB  - All isomers of a four stage rotary molecular motor, dimethyl-tetrahydro
      bi(cyclopenta[alpha]napthal-enylidene), are studied with ultrafast transient
      absorption spectroscopy. Single and two pulse excitations (pump and delayed
      repump with a different wavelength) are used to optically probe the excited state
      dynamics. These measurements demonstrate that this motor is not only designed for
      unidirectional isomerization, but is also "primed" for efficient rotary motion.
      The yield for photoisomerization from the stable P-cis isomer to the metastable M
      trans isomer is 85% +/- 10%, while the yield for the undesired back reaction is
      ca. 0.08 (+0.02, -0.05). The yield for photoisomerization from stable P-trans to
      the metastable M-cis isomer is ca. 85% +/- 3% and the yield for the back reaction
      is 15% +/- 3%. Excitation of P-trans in the lowest singlet state results in
      formation of a dark state on a 3.6 ps time scale and formation of the M-cis
      isomer on a ca. 12 ps time scale. Excitation of P-cis in the lowest singlet state
      results in formation of a dark state on ca. 13 ps time scale and formation of the
      M-trans isomer on a 71 ps time scale. Excitation of either isomer at 269 nm,
      higher in the excited state manifold, accesses additional excited state pathways,
      but does not change the ultimate product formation. This result suggests that
      pulse sequences accessing higher excited states may provide a tool to manipulate
      the molecular motor. Pulse sequences using a 269 nm pump pulse and a 404 nm
      repump pulse are able to increase the yield of the P-cis to M-trans reaction but
      only decrease the yield of the P-trans to M-cis reaction. These pulse sequences
      are unable to access reaction pathways that bypass the helix inversion step,
      although other wavelengths and time delays might yet provide optical control of
      the entire reaction cycle. We propose intermediates and candidate conical
      intersections between all four isomers.

PMID- 30230334
TI  - Highly Efficient Tuning of Ferromagnetic Spin Interactions in High-Spin Arylamine
      Structures by Incorporation of Spin Bearing Carbazole Units.
AB  - Arylamine moieties oxidized to radical cations are considered promising spin
      bearing units in high-spin-type compounds. Here, we report the first use of
      carbazole-3,6-diamine units as efficient, rigid spin containing units. The use of
      rigid spin bearing units enhances significantly spin exchange interactions. The
      design using density functional theory calculations shows the progressive
      increase of the exchange coupling constant dependent on the considered model
      molecules. Two of the most representative molecules containing flexible (dimer 1)
      and rigid spin coupling unit (dimer 2) were synthesized. Electrochemical and
      pulsed-electron paramagnetic resonance nutation studies showed that both dimers
      can be oxidized to yield a majority of dicationic diradicals exhibiting S = 1
      ground states. The high values of the dimer 2 exchange coupling constant obtained
      both computationally ( J/ kB = 145 K; HHeis. = - JS1 S2) and experimentally ( J/
      kB = 90-100 K) indicate the beneficial role of the carbazole moiety incorporated
      into spin bearing units.

PMID- 30230335
TI  - Excited-State Decay Pathways of Flavin Molecules in Five Redox Forms: The Role of
      Conical Intersections.
AB  - Flavin molecules play an important role in light-driven biological activities.
      They have drawn significant interest for decades because of their rich
      photochemistry. In addition to the well-explored FADH- (anionic hydroquinone),
      which is supposed to be the only catalytic active state to repair DNA lesions,
      other four flavin molecules (i.e., FAD, FAD.-, FADH., and FADH2) in three redox
      forms combined the redox cycle of flavins. Although extensive studies have been
      carried out for steady-state spectroscopic properties of five redox flavins in
      various proteins and solutions, the photochemistry and photophysical properties
      of those different redox states significantly complicate the corresponding
      theoretical studies. In present work, we employed the ab initio wave function
      based CASSCF method to systematically investigate the excited state decay
      pathways of flavins in five redox forms through two approaches. First, the
      comparison of the absorption and emission spectra from both theoretical
      calculation and experiment allows a detailed mapping of the transition properties
      of different redox states in flavins. Second, we identified four kinds of conical
      intersections (CIs) for five different redox states as the possible deactivation
      mechanisms responsible for internal conversion or intersystem crossing from the
      initially populated excited state. The theoretical calculations provide atomic
      details for the photochemical and photophysical properties of flavins on
      photoinduced processes. Our findings highlight the indispensable effects of CIs
      in the excited state decay of flavin molecules and thereby provide basic
      theoretical information for light-driven biological activities.

PMID- 30230336
TI  - Characterization and Biological Activity of a Hydrogen Sulfide-Releasing Red
      Light-Activated Ruthenium(II) Complex.
AB  - Hydrogen sulfide (H2S) is a biological gasotransmitter that has been employed for
      the treatment of ischemia-reperfusion injury. Despite its therapeutic value, the
      implementation of this gaseous molecule for this purpose has required H2S
      releasing prodrugs for effective intracellular delivery. The majority of these
      prodrugs, however, spontaneously release H2S via uncontrolled hydrolysis. Here,
      we describe a Ru(II)-based H2S-releasing agent that can be activated selectively
      by red light irradiation. This compound operates in living cells, increasing
      intracellular H2S concentration only upon irradiation with red light.
      Furthermore, the red light irradiation of this compound protects H9c2
      cardiomyoblasts from an in vitro model of ischemia-reperfusion injury. These
      results validate the use of red light-activated H2S-releasing agents as valuable
      tools for studying the biology and therapeutic utility of this gasotransmitter.

PMID- 30230337
TI  - Cellular Durotaxis Revisited: Initial-Position-Dependent Determination of the
      Threshold Stiffness Gradient to Induce Durotaxis.
AB  - Directional cell movement from a softer to a stiffer region on a culture
      substrate with a stiffness gradient, so-called durotaxis, has attracted
      considerable interest in the field of mechanobiology. Although the strength of a
      stiffness gradient has been known to influence durotaxis, the precise
      manipulation of durotactic cells has not been established due to the limited
      knowledge available on how the threshold stiffness gradient (TG) for durotaxis is
      determined. In the present study, to clarify the principles for the manipulation
      of durotaxis, we focused on the absolute stiffness of the soft region and
      evaluated its effect on the determination of TG required to induce durotaxis.
      Microelastically patterned gels that differed with respect to both the absolute
      stiffness of the soft region and the strength of the stiffness gradient were
      photolithographically prepared using photo-cross-linkable gelatins, and the TG
      for mesenchymal stem cells (MSCs) was examined systematically for each stiffness
      value of the soft region. As a result, the TG values for soft regions with
      stiffnesses of 2.5, 5, and 10 kPa were 0.14, 1.0, and 1.4 kPa/MUm, respectively,
      i.e., TG markedly increased with an increase in the absolute stiffness of the
      soft region. An analysis of the area and long-axis length for focal adhesions
      revealed that the adhesivity of MSCs was more stable on a stiffer soft region.
      These results suggested that the initial location of cells starting durotaxis
      plays an essential role in determining the TG values and furthermore that the
      relationship between the position-dependent TG and intrinsic stiffness gradient
      (IG) of the culture substrate should be carefully reconsidered for inducing
      durotaxis; IG must be higher than TG (IG >= TG). This principle provides a
      fundamental guide for designing biomaterials to manipulate cellular durotaxis.

PMID- 30230338
TI  - Total Biosynthesis of Brassicicenes: Identification of a Key Enzyme for Skeletal
      Diversification.
AB  - The biosynthetic pathway of brassicicenes, derived from the phytopathogen
      Pseudocercospora fijiensis, was fully reconstituted. Heterologous expression of
      the eight genes highly expressed in infected leaf tissues generated a new
      brassicicene derivative as a final product. Together with the characterization of
      P450 from Alternaria brassicicola, a late stage of the biosynthetic pathway,
      which generates remarkable structural diversity, has been proposed. Notably, a
      unique P450 that converts 3 to the structurally distinct 4 and 6 was identified.

PMID- 30230339
TI  - Emulsion Droplets Stabilized by Close-Packed Janus Regular Polygonal Particles.
AB  - In Pickering-Ramsden emulsions, the packing structure of the colloidal particles
      at the liquid-liquid (or liquid-gas) interface significantly affects the
      structure and behavior of the emulsion. Here, using a series of platelike
      particles with regular polygonal shapes and Janus amphiphilicity, we created
      emulsion droplets stabilized by close-packed polygonal particles at the
      interface. The systematic variation of the particle morphology shows that the
      geometrical features of the regular polygons in (curved) planar packing dominate
      over the self-assembled structures. The structures are tessellations of
      triangular, square, and hexagonal particles at the surface for large droplets and
      regular tetrahedral, cubic, and dodecahedral particle shells of triangular,
      square, and pentagonal particles for small droplets, respectively. This work
      creates the possibility of geometrically designing the structure and
      functionality of emulsions.

PMID- 30230340
TI  - Polymorphism in Simvastatin: Twinning, Disorder, and Enantiotropic Phase
      Transitions.
AB  - Simvastatin is one of the most widely used active pharmaceutical ingredients for
      the treatment of hyperlipidemias. Because the compound is employed as a solid in
      drug formulations, particular attention should be given to the characterization
      of different polymorphs, their stability domains, and the nature of the phase
      transitions that relate them. In this work, the phase transitions delimiting the
      stability domains of three previously reported simvastatin forms were
      investigated from structural, energetics, and dynamical points of view based on
      single crystal X-ray diffraction (SCXRD), hot stage microscopy (HSM), and
      differential scanning calorimetry (DSC) experiments (conventional scans and heat
      capacity measurements), complemented with molecular dynamics (MD) simulations.
      Previous assignments of the crystal forms were confirmed by SCXRD: forms I and II
      were found to be orthorhombic ( P212121, Z'/ Z = 1/4) and form III was monoclinic
      ( P21, Z'/ Z = 2/4). The obtained results further indicated that (i) the
      transitions between different forms are observed at 235.9 +/- 0.1 K (form III ->
      form II) and at 275.2 +/- 0.2 K (form II -> form I) in DSC runs carried out at 10
      K min-1 and close to these values when other types of techniques are used (e.g.,
      HSM). (ii) They are enantiotropic (i.e., there is a transition temperature
      relating the two phases before fusion at which the stability order is reversed),
      fast, reversible, with very little hysteresis between heating and cooling modes,
      and occur under single crystal to single crystal conditions. (iii) A nucleation
      and growth mechanism seems to be followed since HSM experiments on single
      crystals evidenced the propagation of an interface, accompanied by a change of
      birefringence and crystal contraction or expansion (more subtle in the case of
      form III -> form II), when the phase transitions are triggered. (iv) Consistent
      with the reversible and small hysteresis nature of the phase transitions, the
      SCXRD results indicated that the molecular packing is very similar in all forms
      and the main structural differences are associated with conformational changes of
      the "ester tail". (v) The MD simulations further suggested that the tail is
      essentially "frozen" in two conformations below the III -> II transition
      temperature, becomes progressively less hindered throughout the stability domain
      of form II, and acquires a large conformational freedom above the II -> I
      transition. Finally, the fact that these transitions were found to be fast and
      reversible suggests that polymorphism is unlikely to be a problem for
      pharmaceutical formulations employing crystalline simvastatin because, if
      present, the III and II forms will readily convert to form I at ambient
      temperature.

PMID- 30230341
TI  - Diversity-Oriented Syntheses of beta-Substituted alpha-Amino gamma-Lactam Peptide
      Mimics with Constrained Backbone and Side Chain Residues.
AB  - alpha- N-(Fmoc)Amino-gamma-lactam dipeptides with a variety of beta-substituents
      were synthesized stereoselectively with minimal beta-elimination by routes
      employing, respectively, Mitsunobu chemistry and cyclic sulfamidate nucleophilic
      ring opening from trans- and cis-beta-hydroxy-alpha-amino-gamma-lactam
      precursors. This diversity-oriented method provides stereochemically pure
      dipeptide mimics bearing Cys, Ser, Thr, Dap, Dab, His, and other amino acid
      residues with constrained backbone and side chain conformations.

PMID- 30230342
TI  - Update of the Functional Mitochondrial Human Proteome Network.
AB  - Because of the pivotal role of mitochondrial alterations in several diseases, the
      Human Proteome Organization (HUPO) has promoted in recent years an initiative to
      characterize the mitochondrial human proteome, the mitochondrial human proteome
      project (mt-HPP). Here we generated an updated version of the functional
      mitochondrial human proteome network, made by nodes (mitochondrial proteins) and
      edges (gold binary interactions), using data retrieved from neXtProt, the
      reference database for HPP metrics. The principal new concept suggested was the
      consideration of mitochondria-associated proteins (first interactors), which may
      influence mitochondrial functions. All of the proteins described as mitochondrial
      in the sublocation or the GO Cellular Component sections of neXtProt were
      considered. Their other subcellular and submitochondrial localizations have been
      analyzed. The network represents the effort to collect all of the high-quality
      binary interactions described so far for mitochondrial proteins and the
      possibility for the community to reuse the information collected. As a proof of
      principle, we mapped proteins with no function, to speculate on their role by the
      background knowledge of their interactors, and proteins described to be involved
      in Parkinson's Disease, a neurodegenerative disorder, where it is known that
      mitochondria play a central role.

PMID- 30230343
TI  - Flexible and Fast Mapping of Peptides to a Proteome with ProteoMapper.
AB  - Bottom-up proteomics relies on the proteolytic or chemical cleavage of proteins
      into peptides, the identification of those peptides via mass spectrometry, and
      the mapping of the identified peptides back to the reference proteome to infer
      which possible proteins are identified. Reliable mapping of peptides to proteins
      still poses substantial challenges when considering similar proteins, protein
      families, splice isoforms, sequence variation, and possible residue mass
      modifications, combined with an imperfect and incomplete understanding of the
      proteome. The ProteoMapper tool enables a comprehensive and rapid mapping of
      peptides to a reference proteome. The indexer component creates a segmented index
      for an input proteome from a FASTA or PEFF file. The ProMaST component provides
      ultrafast mapping of one or more input peptides against the index. ProteoMapper
      allows searches that take into account known sequence variation encoded in PEFF
      files. It also enables fuzzy searches to find highly similar peptides with
      residue order changes or other isobaric or near-isobaric substitutions within a
      specified mass tolerance. We demonstrate an example of a one-hit-wonder
      identification in PeptideAtlas that may be better explained by a combination of
      catalogued and uncatalogued sequence variation in another highly observed
      protein. ProteoMapper is a free and open source, available for local use after
      downloading, embedding in other applications, as an online web tool at
      http://www.peptideatlas.org/map , and as a web service.

PMID- 30230345
TI  - Recommended Reading from the National University of Ireland Galway Regenerative
      Medicine Institute (REMEDI) Lung Biology Group Fellows.

PMID- 30230344
TI  - From Molecular Arrangement to Macroscopic Wetting of Ionic Liquids on the Mica
      Surface: Effect of Humidity.
AB  - To optimize the wetting performance of ionic liquids (ILs) on solid surfaces,
      which is important in catalysis, lubrication, and energy storage, it is critical
      to control the molecular arrangement of ILs at the IL/solid interface. Here, we
      report our experimental results, showing that tuning humidity is a facile and
      effective approach manipulating the molecular arrangement and thus controlling
      the macroscopic wettability of ILs on the mica surface. Fourier transform
      infrared spectroscopy, contact angle testing, and atomic force microscopy results
      showed that with the increase of humidity, more water adsorbs on the mica
      surface, which dissolves and mobilizes K+ on the mica. As a result, the cations
      of ILs occupy the empty spot left by the K+ and initiate the layering of ILs. The
      water-enabled ion exchange and IL layering processes result in not only the
      decrease of the IL contact angle on the mica but also the time-dependent contact
      angle. The finding here potentially provides a new dimension tailoring the
      performance of ILs at the IL/solid interface.

PMID- 30230346
TI  - The LIBERATE Trial: Options to Reduce the Risk of Post-Procedural Pneumothorax
      and Length of Stay.

PMID- 30230347
TI  - A Nonhospitable Host: Targeting Cellular Factors as an Antiviral Strategy for
      Respiratory Viruses.

PMID- 30230348
TI  - P311 Promotes Lung Fibrosis via Stimulation of TGF-beta1, 2 and 3 Translation.
AB  - Interstitial lung fibrosis, a frequently idiopathic and fatal disease, has been
      linked to the increased expression of profibrotic TGF-betas. P311 is an RNA
      binding protein, which stimulates TGF-beta1, 2 and 3 translation in several cell
      types through its interaction with the eukaryotic translation initiation factor
      3b. Here we report that P311 is switched on in the lungs of Idiopathic pulmonary
      fibrosis (IPF) patients and in the mouse model of bleomycin (BLM)-induced
      pulmonary fibrosis. To assess the in vivo role of P311 in lung fibrosis, BLM was
      instilled into the lungs of P311 knockout (KO) mice where fibrotic changes were
      significantly decreased in tandem with a reduction in TGF-beta1, 2 and 3
      levels/activity compared to BLM-treated wild type (WT) mice. Complementing these
      findings, forced P311 expression increased TGF-betas level/activity in mouse and
      human lung fibroblasts, thereby leading to an activated phenotype with increased
      collagen production, as seen in IPF. Consistent with a specific effect of P311 on
      TGF-betas translation, TGF-beta1, 2 and 3 neutralizing antibodies downregulated
      P311-induced collagen production by lung fibroblasts. Furthermore, treatment of
      BLM-exposed P311 KOs with recombinant TGF-beta1, 2 and 3 induced pulmonary
      fibrosis to a degree similar to that found in BLM-treated WT mice. These studies
      demonstrate the essential function of P311 in TGF-betas-mediated lung fibrosis.
      Targeting P311 could prove efficacious in ameliorating the severity of IPF while
      circumventing the development of autoimmune complications and toxicities
      associated with the use of global TGF-beta inhibitors.

PMID- 30230349
TI  - Reply to: The LIBERATE trial: Options to Reduce the Risk of Post-Procedural
      Pneumothorax and Length of Stay.

PMID- 30230350
TI  - Uncomfortable Uncertainty: Do OTC Analgesics Disrupt Fetal Germ Cell Development?

PMID- 30230351
TI  - The Medical Perspective on a Disease Life Cycle. Sepsis in the Realm of
      Implementation Science.

PMID- 30230352
TI  - Induced Pluripotent Stem Cells for Primary Ciliary Dyskinesia Modeling and
      Personalized Medicine.
AB  - Primary ciliary dyskinesia (PCD) is a rare and heterogeneous genetic disorder
      that affects the structure and function of motile cilia. In the airway
      epithelium, impaired ciliary motion results in reduced or absent mucociliary
      clearance that leads to the appearance of chronic airway infection, sinusitis,
      and bronchiectasis. Currently, there is no effective treatment for PCD, and
      research is limited by the lack of convenient models to study this disease and
      investigate innovative therapies. Furthermore, the high heterogeneity of PCD
      genotypes is likely to hinder the development of a single therapy for all
      patients. The generation of patient-derived, induced pluripotent stem cells, and
      their differentiation into airway epithelium, as well as genome editing
      technologies, could represent major tools for in vitro PCD modeling and for
      developing personalized therapies. Here, we review PCD pathogenesis and then
      discuss how human induced pluripotent stem cells could be used to model this
      disease for the development of innovative, patient-specific biotherapies.

PMID- 30230353
TI  - Intercellular Communication between Airway Epithelial Cells is Mediated by
      Exosome-Like Vesicles.
AB  - Airway epithelium structure/function can be altered by local inflammatory/immune
      signals, and this process is called epithelial remodeling. The mechanism by which
      this innate response is regulated, which causes mucin/mucus overproduction, is
      largely unknown. Exosomes are nano-vesicles that can be secreted and internalized
      by cells to transport cellular cargo, such as proteins, lipids, and miRNA. The
      objective of this study was to understand the role exosomes play in airway
      remodeling through cell-cell communication. We utilized two different human
      airway cell cultures: primary tracheobronchial (HTBE) cells and a cultured airway
      epithelial cell line (Calu-3). After intercellular exosomal transfer,
      comprehensive proteomic and genomic characterization of cell secretions and
      exosomes was performed. Quantitative proteomics and exosomal miRNA analysis
      profiles indicated that the two cell types are fundamentally distinct. HTBE cell
      secretions were typically dominated by fundamental innate/protective proteins,
      including mucin MUC5B, and Calu-3 cell secretions were dominated by pathology
      associated proteins, including mucin MUC5AC. After exosomal transfer/intake,
      approximately 20% of proteins, including MUC5AC and MUC5B, were significantly
      altered in HTBE secretions. After exosome transfer, approximately 90 miRNAs (~4%)
      were upregulated in HTBE exosomes, whereas Calu-3 exosomes exhibited a preserved
      miRNA profile. Together, our data suggest that the transfer of exosomal cargo
      between airway epithelial cells significantly alters the qualitative and
      quantitative profiles of airway secretions, including mucin hypersecretion, and
      the miRNA cargo of exosomes in target cells. This finding indicates that cellular
      information can be carried between airway epithelial cells via exosomes, which
      may play an important role in airway biology and epithelial remodeling.

PMID- 30230354
TI  - Superflare Ultraviolet Impact on Kepler-96 System: A Glimpse of Habitability When
      the Ozone Layer First Formed on Earth.
AB  - Kepler-96 is an active solar-type star harboring a Super-Earth planet in close
      orbit. Its age of 2.3 gigayears is the same as the Sun when there was a
      considerable increase of oxygen in Earth's atmosphere due to micro-organisms
      living in the ocean. We present the analysis of superflares seen on the transit
      light curves of Kepler-96b. The model used here simulates the planetary transit
      in a flaring star. By fitting the observational data with this model, it is
      possible to infer the physical properties of the flares, such as their duration
      and the energy released. We found three flares within the energy range of
      superflares, where the biggest superflare observed was found to have an energy of
      1.81 * 1029 J (1.81 * 1035 ergs). The goal is to analyze the biological impact of
      these superflares on a hypothetical Earth in the habitable zone of Kepler-96,
      assuming this planet has protection through different scenarios: an Archean and
      present-day atmospheres. Also, we compute the attenuation of the flare
      ultraviolet (UV) radiation through an Archean ocean. The conclusion is that
      considering the increase in the UV flux by the strongest superflare emission,
      Escherichia coli and Deinococcus radiodurans could survive on the surface of the
      planet only if there was an ozone layer present on the planet atmosphere.
      However, they could escape from the hazardous UV effects at a depth of 28 and 12
      m below the ocean surface, respectively. For smaller superflares contribution, D.
      radiodurans could survive in the surface even in an Archean atmosphere with no
      ozone.

PMID- 30230355
TI  - Probability-driven 3D pharmacophore mapping of antimycobacterial potential of
      hybrid molecules combining phenylcarbamoyloxy and N-arylpiperazine fragments.
AB  - The current study examines in silico characterization of the structure-inhibitory
      potency for a set of phenylcarbamic acid derivatives containing an N
      arylpiperazine scaffold, considering the electronic, steric and lipophilic
      properties. The main objective of the ligand-based modelling was the systematic
      study of classical comparative molecular field analysis (CoMFA)/comparative
      molecular surface analysis (CoMSA) performance for the modelling of in vitro
      efficiency observed for these phenylcarbamates, revealing their inhibitory
      activities against a virulent Mycobacterium tuberculosis H37Rv strain. We
      compared the findings of efficiency modelling produced by a standard 3D
      methodology (CoMFA) and its neural counterparts (CoMSA) regarding multiple
      training/test subsets and variables used. Moreover, systematic space inspection,
      splitting values into the analysed training/test subsets, was performed to
      monitor statistical estimator performance while mapping the probability-driven
      pharmacophore pattern. Consequently, a 'pseudo-consensus' 3D-quantitative
      structure-activity relationship (3D-QSAR) approach was applied to retrieve an
      'average' pharmacophore hypothesis by the investigation of the most densely
      populated training/test subpopulations to specify the potentially important
      factors contributing to the inhibitory activity of phenylcarbamic acid analogues.
      In addition, examination of descriptor-based similarity with a principal
      component analysis (PCA) procedure was employed to visualize noticeable
      variations in the performance of these molecules with respect to their structure
      and activity profiles.

PMID- 30230356
TI  - Nurses' knowledge and deliberations crucial to Barcoded Medication Administration
      technology in a Dutch hospital: Discovering nurses' agency inside ruling.
AB  - This article shows how Barcoded Medication Administration technology
      institutionally organizes and rules the daily actions of nurses. Although it is
      widely assumed that Barcoded Medication Administration technology improves
      quality and safety by reducing the risk of human error, little research has been
      done on how this technology alters the work of nurses. Drawing on empirical and
      conceptual strategies of analysis, this qualitative study used certain tools of
      institutional ethnography to provide a view of how nurses negotiate Barcoded
      Medication Administration technology. The approach also uses elements from
      practice theory in order to discern how technology operates as a player on the
      field instead of being viewed as a 'mere' tool. A literature review preceded
      participant observation, whereby 17 nurses were followed and data on an
      orthopaedic ward were collected over a period of 9 months in 2011 and 2012.
      Barcoded Medication Administration technology relies on nurses' knowledge to
      mediate between the embedded logics of its design and the unpredictable needs of
      patients. Nurses negotiate their own professional logic of care in the form of
      moment-to-moment deliberations which subvert the ruling frame of the barcoded
      system and its objectified model of patient safety. The logic of Barcoded
      Medication Administration technology differs from the logic of nursing care, as
      this technology presumes medication distribution to be linear, even though nurses
      follow another line of actor-bound safety practices that we characterize as
      'deliberations'.

PMID- 30230357
TI  - Physical and sociocultural facilitators and barriers to access and utilization of
      a nutrition program in rural Malawi: a qualitative study.
AB  - Childhood stunting holds consequences for child development. A nutrition program
      delivering small-quantity lipid based nutrient supplements (SQ-LNS) to children 6
      23 months and child feeding messages was implemented in Malawi to reduce
      stunting. This study sought to understand the facilitators and barriers to
      program participation using in-depth interviews, pile sorts, direct observations,
      and focus group discussions with caretakers, village leaders and program
      volunteers. Perceptions of the LNS were positive, and visible changes in child
      health contributed to program participation. Conflicting priorities that
      prevented monthly collection of SQ-LNS and limited knowledge of child feeding
      messages constituted barriers to program participation.

PMID- 30230359
TI  - Assembling the 'Fitbit subject': A Foucauldian-sociomaterialist examination of
      social class, gender and self-surveillance on Fitbit community message boards.
AB  - The rise of fitness-tracking devices such as the Fitbit in personal health and
      wellness is emblematic of the use of data-gathering health and fitness
      technologies by institutions to create a surveillance regime. Using postings on
      Fitbit community message boards and the theoretical frames of Michel Foucault and
      sociomaterialist scholars, the goal of this article is to analyse the experiences
      of those who choose to self-track using a Fitbit and the constellation of
      barriers and facilitators (human and non-human) related to social class and
      gender that enable and constrain one's ability to use a Fitbit as intended.
      First, we examine the social class assumptions of Fitbit as a risk management
      tool in the workplace, illustrating what elements must come together - both human
      and non-human - to create an environment that enables walking throughout the
      workday to combat the risks of sedentary work. Second, we explore the ways that
      Fitbit users 'confessed' to their past inactivity and how gendered home labour
      differently enables and constrains some of the users' abilities to act on their
      confessions. Ultimately, one's ability to engage in the idealized use of the
      Fitbit in the minds of its users, or what we term the 'Fitbit subject
      assemblage', is structured by numerous material and social factors that must be
      taken into account when examining the mechanics of power in fitness tracking.

PMID- 30230358
TI  - Feasibility of clinical hypnosis for transesophageal echocardiography in children
      and adolescents.
AB  - BACKGROUND: The use of hypnosis in children has been described more than two
      centuries ago, with a more recent research and clinical application. There is
      currently a good level of evidence for the efficacy of clinical hypnosis in
      children for minor surgery, medical procedures or pain management. The use of
      clinical hypnosis, in paediatric cardiology, for invasive procedures such as
      transesophageal echocardiography, has not been reported. AIMS: This study
      evaluated the feasibility of clinical hypnosis in children undergoing
      transesophageal echocardiography. METHOD: This prospective, non-randomised, cross
      sectional study was carried out over 24 months in a paediatric cardiology
      referral centre. All children aged 10-18 years requiring a transesophageal
      echocardiography examination, outside the operating room and the catheterisation
      laboratory, were eligible for the study. Children and families could choose
      between transesophageal echocardiography under clinical hypnosis or under general
      anaesthesia (<15 years) or sedation (?15 years). RESULTS: We included 16 children
      aged 11-18 years (seven girls, mean age 14.1+/-2.5 years). The hypnotic state was
      achieved for 15 out of the 16 participating children (94%). The transesophageal
      echocardiography examination could be completely achieved with a full diagnosis
      for 15 out of 16 children (94%). In all cases, a transesophageal echocardiography
      examination under clinical hypnosis provided a complete diagnosis. CONCLUSION:
      This study demonstrated that hypnosis was feasible and effective for
      transesophageal echocardiography in adolescents and might be a good alternative
      to general anaesthesia. Further study with larger numbers of subjects and more
      diverse congenital cardiac conditions are needed to confirm the results in a more
      diverse sample.

PMID- 30230360
TI  - Knowledge and awareness of HIV self-testing among Australian gay and bisexual
      men: a comparison of never, sub-optimal and optimal testers willingness to use.
AB  - This paper explores the willingness to use and pay for HIV Self-testing (HIVST)
      among Australian gay and bisexual men (GBM). Bivariate and univariate
      multinominal logistic regression of data from an online survey was performed.
      Thirty-one (13%) had never HIV tested and 41.9% (88) were testing sub-optimally
      by Australian guidelines. Half (58.4%, 136) had never heard of HIVST, however,
      56.2% (131) reported willingness to use HIVST, with sub-optimal (OR=2.13; p <
      0.01) and never-testers (OR=2.01; p < 0.10) significantly more likely to do so
      than optimal-testers. Most were confident (51.7%, 119) or somewhat confident
      (29.1%, 67) accessing support following a reactive result, however, never-testers
      were significantly less confident compared to previous testers (OR=3.47; p<
      0.05). Less than a quarter (23.6%, 57) were willing to pay for a kit with AUD$15
      (R2 = 0.9882) the estimated preferred price. This research confirms that HIVST is
      an important and accepted adjunct to established HIV testing modalities,
      particularly among sub-optimal and never-testers and that online (61.6%, 143) or
      clinic-based (61.6%, 143) dissemination are preferred. Research examining how
      best to disseminate HIVST in a range of safe and effective models needs to
      continue to ensure HIVST is part of a comprehensive strategy that facilitates
      usage and linkages to care.

PMID- 30230361
TI  - Secukinumab for psoriatic arthritis: comparative effectiveness versus licensed
      biologics/apremilast: a network meta-analysis.
AB  - AIM: A network meta-analysis using randomized controlled trial data compared
      psoriatic arthritis (PsA) outcomes (American College of Rheumatology [ACR],
      Psoriasis Area Severity Index [PASI] and Psoriatic Arthritis Response Criteria
      [PsARC] response rates) at 12-16 weeks for secukinumab, adalimumab, apremilast,
      certolizumab, etanercept, golimumab, infliximab and ustekinumab. PATIENTS &
      METHODS: Trials were identified by systematic review. Separate networks were
      developed for the full-study populations, biologic-naive patients and biologic
      experienced patients. RESULTS: In the full populations, secukinumab, adalimumab,
      golimumab and infliximab demonstrated the highest ACR response rates. Secukinumab
      and infliximab demonstrated the highest PASI response rates, and infliximab and
      etanercept demonstrated the highest PsARC response rates. CONCLUSION: In the full
      populations, secukinumab demonstrated good efficacy across all outcomes. All
      treatments for active PsA included in this comprehensive network meta-analysis
      demonstrated superiority to placebo.

PMID- 30230363
TI  - Presence of carbapenem-resistant bacteria in soils affected by illegal waste
      dumps.
AB  - The carbapenem-resistant bacteria (CRB) are currently at the top of the WHO
      priority list of bacteria that pose the greatest threat to human health.
      Considering that soil is one of the important environments for the emergence of
      antibiotic-resistant bacteria, we isolated and quantified cultivable CRB in soils
      across Croatia, including ones affected by illegal dumps. We cultivated CRB at
      two temperatures, distinguishing between the intrinsically resistant CRB (37
      degrees C, mostly Stenotrophomonas spp.) and the ones that are presumably human
      associated and clinically relevant (42 degrees C, Acinetobacter sp.,
      Enterobacteriaceae, Burkholderia spp.). Our study demonstrated that
      distinguishing between the two offers a better insight into the diversity of CRB
      in the environment. The ones cultivated at 37 degrees C were found in almost all
      soil samples, while the presumably clinically relevant ones were absent from
      uncontaminated pasture and grassland, indicating that human-associated CRB are
      unlikely to be found in soils spared from anthropogenic influence.

PMID- 30230364
TI  - Acquired CFTR Dysfunction and Radiographic Bronchiectasis in Current and Former
      Smokers: A Cross-Sectional Study.

PMID- 30230365
TI  - Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse
      Events: Methods for item selection in industry-sponsored oncology clinical
      trials.
AB  - As new cancer treatment regimens demonstrate increased potential to improve
      patients' survival, more focus is directed toward the quality of that extension
      of life and to obtaining additional information from patients regarding their
      experience with treatment. The utility of capturing patient-reported treatment
      related symptoms to complement traditional clinician-rated symptomatic adverse
      event reporting is well-documented. The National Cancer Institute's Patient
      Reported Outcomes version of the Common Terminology Criteria for Adverse Events
      is an item library aimed at capturing patient-reported symptoms to inform the
      patient perspective on a treatment's tolerability. The U.S. Food and Drug
      Administration has recommended using the Patient-Reported Outcomes version of the
      Common Terminology Criteria for Adverse Events in clinical trials. A practical
      guideline is needed to inform a priori selection of specific Patient-Reported
      Outcomes version of the Common Terminology Criteria for Adverse Events items for
      use in any given industry-sponsored oncology clinical trial. Standardizing this
      selection process will foster systematic and consistent data collection as part
      of drug development and enhance our knowledge on how to use patient-relevant
      information as part of a treatment's risk/benefit assessment. This article
      presents methods and consensus recommendations for selecting specific Patient
      Reported Outcomes version of the Common Terminology Criteria for Adverse Events
      items to include in early-phase and late-phase oncology clinical trials.

PMID- 30230362
TI  - Control of Confounding and Reporting of Results in Causal Inference Studies:
      Guidance for Authors from Editors of Respiratory, Sleep, and Critical Care
      Journals.

PMID- 30230366
TI  - Using geographically weighted regression for social inequality analysis:
      association between mentally unhealthy days (MUDs) and socioeconomic status (SES)
      in U.S. counties.
AB  - This research explores geographic variability of factors on social inequality
      related to mental health in the United States using county-level data in 2014.
      First, we account for complex design factors in Behavioural Risk Factor
      Surveillance System (BRFSS) data such as clustering, stratification, and sample
      weight using Complex Samples General Linear Model (CSGLM). Then, three variables
      are used in the model as indicators of social inequality, low socioeconomic
      status (SES): unemployment, education status, and social association status. A
      geographically weighted regression analysis is applied to examine the spatial
      variations in the associations of mentally unhealthy days (MUDs) with the
      indicators of SES in the United States. The results demonstrate that unemployment
      and education level show global positive and negative influences respectively on
      MUDs. Social association status ranged from positive to negative across the
      United States, implying some geographic clustering. These findings suggest that
      social and health policies should be adjusted to address the different effects of
      indicators of social inequality on mental health across different social
      characteristics of communities to more effectively manage mental health problems.

PMID- 30230367
TI  - Palmitate aggravates proteinuria-induced cell death and inflammation via CD36
      inflammasome axis in the proximal tubular cells of obese mice.
AB  - High levels of serum free fatty acids (FFAs) and proteinuria have been implicated
      in the pathogenesis of obesity-related nephropathy. CD36, a class B scavenger
      receptor, is highly expressed in the renal proximal tubules and mediates FFA
      uptake. It is not clear whether FFA- and proteinuria-mediated CD36 activation
      coordinates NLRP3 inflammasomes to induce renal tubular injury and inflammation.
      In this study, we investigated the roles of CD36 and NLRP3 inflammasomes in FFA
      induced renal injury in high-fat diet (HFD)-induced obesity. HFD-fed C57BL/6 mice
      and palmitate-treated HK2 renal tubular cells were used as in vivo and in vitro
      models. Immunohistochemical staining showed that CD36, IL-1beta, and IL-18 levels
      increased progressively in the kidneys of HFD-fed mice. Sulfo-N-succinimidyl
      oleate (SSO), a CD36 inhibitor, attenuated the HFD-induced upregulation of NLRP3,
      IL-1beta, and IL-18 and suppressed the colocalization of NLRP3 and ASC in renal
      tubular cells. In vitro, SSO abolished the palmitate-induced activation of IL
      1beta, IL-18, and caspase-1 in HK2 proximal tubular cells. Furthermore, treatment
      with SSO and the knockdown of caspase-1 expression by siRNA both inhibited
      palmitate-induced cell death and apoptosis in HK2 cells. Collectively, palmitate
      causes renal tubular inflammation, cell death, and apoptosis via the
      CD36/NLRP3/caspase-1 axis, which may explain, at least in part, the mechanism
      underlying FFA-related renal tubular injury. The blockade of CD36-induced
      cellular processes is therefore a promising strategy for treating obesity-related
      nephropathy.

PMID- 30230368
TI  - The Podocyte Protease Web: Uncovering the Gatekeepers of Glomerular Disease.
AB  - Proteases regulate glomerular physiology. The last decade has revealed a
      multitude of podocyte proteases that govern the glomerular response to numerous
      chemical, mechanical and metabolic cues. These proteases form a protein signaling
      web that integrates stress stimuli and serves as a key controller of the
      glomerular microenvironment. Both the extracellular and intracellular proteolytic
      networks are perturbed in focal segmental glomerulosclerosis, as well as
      hypertensive and diabetic nephropathy. Accordingly, the highly-intertwined
      podocyte protease web is an integrative part of the podocyte's damage response.
      Novel mass-spectrometry based technologies will help to untangle this proteolytic
      network: functional readouts acquired from deep podocyte proteomics, single
      glomerular proteomics, and degradomics have exposed unanticipated protease
      activity in podocytes. Future efforts should characterize the interdependency and
      upstream regulation of key proteases, along with their role in promoting tissue
      heterogeneity in glomerular diseases. These efforts will not only illuminate the
      machinery of podocyte proteostasis, but also reveal avenues for therapeutic
      intervention in the podocyte protease web.

PMID- 30230369
TI  - Stay in the Loop: New Insights about Randall's Plaques and Stone Disease.

PMID- 30230370
TI  - Tracking renal injury using multi-parametric MRI.

PMID- 30230371
TI  - Proteomic approaches in kidney disease biomarker discovery.
AB  - Biomarkers have the potential to greatly facilitate diagnosis and treatment of
      patients with various forms of kidney disease. State-of-the-art mass spectrometry
      based methods possess the capability, on a proteome scale and in an unbiased
      manner, to detect alterations in protein abundances and/or post-translational
      modifications in plasma, urine or tissue. Such approaches can provide a large
      unbiased database to facilitate identification of potential biomarkers. In the
      diagnosis of kidney diseases, urine is usually a more favorable specimen than
      plasma and kidney tissue due to its non-invasive collection and simplicity of
      processing. However, whether analysis of proteins in urine faithfully reflects
      their changes in the kidney tissue remains unclear. The use of proteomics to
      analyze kidney tissue samples collected during late-stage kidney diseases has
      also recently gathered pace. The goal of this mini-review is to provide an
      overview of the proteomic technologies currently applied to studies of kidney and
      their limitations, present existing kidney and urine proteome databases, and
      highlight a few applications of such approaches in kidney disease biomarker
      discovery.

PMID- 30230372
TI  - Cross-Contamination with Gluten by Using Kitchen Utensils: Fact or Fiction?
AB  - A risk of cross-contamination exists when preparing a gluten-free (GF) meal in
      kitchen facilities that usually handle gluten-containing (GC) foods. Cross
      contamination with gluten may occur during the preparation or cooking process;
      however, published data are lacking on gluten cross-contamination from
      kitchenware. This study was conducted to determine whether cross-contamination
      occurs through shared domestic kitchenware and, if so, which cleaning method is
      most reliable for avoiding this cross-contamination. Kitchenware (wooden spoon,
      colander, ladle, and knife) previously used to cook and/or prepare GC foods was
      used for the preparation of GF foods (bread and pasta). The gluten concentration
      of the GF foods was then determined using an established enzyme-linked
      immunosorbent assay. A PCR assay was also used to detect the presence of wheat
      omega-gliadin DNA in the food samples. Three cleaning methods were assessed to
      determine the concentrations of gluten and wheat DNA in GF foods cooked with
      utensils cleaned directly after the preparation of GC foods. Contrary to our
      expectations, gluten was not detected in relevant and quantifiable amounts in our
      samples (<20 mg/kg). The cleaning method used did not influence gluten
      concentrations: all samples contained <10 mg/kg. Based on PCR analyses, the only
      sample with lower cycle threshold ( CT) values (i.e., higher concentration of
      wheat DNA) was from the contaminated ladle used to serve GF pasta. This outcome
      led to the hypothesis that shared ladles pose a higher risk for contamination of
      GF foods than do shared wooden spoons, colanders, or knives. Cross-contamination
      with gluten in a kitchen environment may occur, but kitchen utensils used for
      preparing GC pasta and for cutting GC bread should not pose a relevant problem to
      patients with celiac disease, at least in a domestic environment.

PMID- 30230373
TI  - Optimizing the Addition of Functional Plant Extracts and Baking Conditions To
      Develop Acrylamide-Free Pita Bread.
AB  - The effects of using freeze-dried extracts (FDEs) of spearmint ( Mentha spicata),
      fennel ( Foeniculum vulgare), and turmeric ( Curcuma longa) as well as adjusting
      the baking temperature and time on acrylamide formation in pita bread were
      investigated to obtain the most acceptable conditions that produced the lowest
      acrylamide concentrations. A Box-Behnken design was adopted for optimization of
      the pita bread formulations by adding FDEs (3 to 25 g/100 g of wheat flour) and
      adjusting the baking temperature (200 to 300 degrees C) and baking time (3 to 11
      min), and the effects of these changes on color parameters, phytochemical
      attributes, and acrylamide concentrations were evaluated. Increasing the
      concentration of FDE and decreasing the baking temperature and time considerably
      decreased the acrylamide concentration in bread for all experimental trials. No
      acrylamide was detected in pita bread formulated with 25 g of mint FDE/100 g of
      wheat flour and baked at 250 degrees C for 3 min, formulated with 25 g of mint or
      fennel FDE/100 g and baked at 300 degrees C for 7 min, formulated with 3 g of
      mint, fennel, or turmeric FDE/100 g and baked at 200 degrees C for 7 min,
      formulated with 14 g of mint FDE/100 g and baked at 300 degrees C for 3 min, and
      formulated with 25 g of mint or fennel FDE/100 g and baked at 200 degrees C for 7
      min. Pita breads formulated with fennel and turmeric FDE were given high sensory
      scores.

PMID- 30230374
TI  - Radio-Frequency Processing for Inactivation of Salmonella enterica and
      Enterococcus faecium NRRL B-2354 in Black Peppercorn.
AB  - Several Salmonella outbreaks linked to black pepper call for effective
      inactivation processes, because current decontamination methods result in quality
      deterioration. Radio-frequency (RF) heating provides a rapid heating rate and
      volumetric heating, resulting in a shorter come-up time. This allows for choosing
      a high-temperature and short-time combination to achieve the desired inactivation
      with minimal quality deterioration. The objectives of this study were to evaluate
      RF heating for inactivation of Salmonella enterica and Enterococcus faecium in
      black peppercorn and evaluate quality changes of RF-treated black peppercorn.
      Black peppercorns were inoculated with a five-strain cocktail of Salmonella or E.
      faecium to attain initial population levels of 6.8 and 7.3 log CFU/g,
      respectively, and were then adjusted to a moisture content of 12.7% (wet basis)
      and a water activity of 0.60 at room temperature. A stability test was performed
      to quantify the microbial reduction during inoculation and equilibration before
      RF heating inactivation. During RF heating, the cold spot was determined to be at
      the center on the top surface of the treated sample. In addition to inoculating
      the entire sample, an inoculated packed sample was placed at the cold spot of the
      tray. An RF heating time of 2.5 min provided a 5.31- and 5.26-log CFU/g reduction
      in the entire sample contained in the tray for Salmonella and E. faecium,
      respectively. Color parameters (L*, a*, b*), piperine content, total phenolics,
      scavenging activity, and most of the volatile compounds of 2.5-min RF-treated
      samples were not significantly different from those of the control samples. These
      data suggest that RF heating is a promising thermal inactivation treatment for
      Salmonella without significant quality deterioration, and E. faecium seems to be
      a suitable surrogate for Salmonella to validate the efficacy of RF heating of
      black peppercorn.

PMID- 30230375
TI  - A comparative assessment of bracket survival and adhesive removal time using
      flash-free or conventional adhesive for orthodontic bracket bonding: A split
      mouth randomized controlled clinical trial.
AB  - OBJECTIVES:: To compare bracket survival and adhesive removal time between a
      flash-free and a conventional adhesive for orthodontic bracket bonding. MATERIALS
      AND METHODS:: Forty-five consecutive patients had their maxillary incisors,
      canines, and premolars bonded with ceramic brackets using a flash-free adhesive
      (APC Flash-Free Adhesive, 3M Unitek, Monrovia, Calif) on one side and a
      conventional adhesive (APCII Adhesive, 3M Unitek) on the other side. The side
      allocation was randomized. Bracket failure was recorded at 4-week intervals. The
      adhesive remnant index (ARI) was scored on debond and adhesive removal timed to
      the nearest second. The primary outcome was adhesive removal time per quadrant.
      Secondary outcomes were bracket failure rate, time to first-time failure of a
      bracket, and ARI score on debond. Paired t-tests were used to compare adhesive
      removal times and ARI scores between the adhesives with P < .05 considered
      statistically significant. RESULTS:: Bracket failure rates were 4.3% for the
      flash-free adhesive and 1.9% for the conventional adhesive, with mean times to
      first-time failure of 31 weeks for the flash-free adhesive and 42 weeks for the
      conventional adhesive; neither failure rates nor times to first failure were
      significantly different. Although the flash-free adhesive left significantly more
      adhesive on the tooth surface after debonding, the adhesive removal times were
      22.2% shorter than with the conventional adhesive. CONCLUSIONS:: Bracket survival
      with the flash-free adhesive was equivalent to the conventional adhesive when
      ceramic brackets were bonded. Adhesive removal was significantly faster when
      using the flash-free adhesive, which may result in time savings of more than 20%
      compared with the conventional adhesive.

PMID- 30230376
TI  - Reliability and reproducibility of the method of assessment of midpalatal suture
      maturation: A tomographic study.
AB  - OBJECTIVES:: To assess reliability and reproducibility of the individual
      assessment of midpalatal suture maturation in computed tomography among
      orthodontists and radiologists for potential diagnosis application. MATERIALS AND
      METHODS:: Sixty axial slices from cone-beam computed tomography and multi-slice
      CT scans of patients aged between 11 and 21 years old (33 females and 27 males)
      were selected. For the investigation of reliability and reproducibility of the
      method, two groups of examiners were established. The first group consisted of 11
      orthodontists and the second consisted of 10 radiologists. Each group examined
      the images and performed individual assessment of the midpalatal suture
      maturation method twice within an interval of 21 days. During the first and
      second analyses, the sequence of images was randomized to reduce potential bias.
      Weighted Cohen's kappa was performed to assess inter- and intra-examiners'
      agreement. The percentage of perfect agreement and the number of stages apart for
      each disagreement were calculated. The significance level was P < .05. RESULTS::
      The overall inter-examiner agreement was satisfactory in the first (kappaw: 0.37)
      and the second (kappaw: 0.34) analyses. Intra-examiner agreement outcomes were
      similar between orthodontists (kappaw: 0.44) and radiologists (kappaw: 0.41). The
      percentage of perfect agreement was 43.2%. CONCLUSIONS:: The method for
      individual assessment of midpalatal suture maturation revealed potential
      reliability and reproducibility. However, the agreement rate observed in the
      present study was not high enough for a method designed for routine clinical
      applications.

PMID- 30230377
TI  - Effect of loaded orthodontic miniscrew implant on compressive stresses in
      adjacent periodontal ligament.
AB  - OBJECTIVES:: To describe the relationship between the proximity of miniscrew
      implants (MSIs) to the periodontal ligament (PDL) and stress in the PDL under
      different load magnitudes and different bone properties. MATERIALS AND METHODS::
      Sixteen subject-specific finite element models of the region of the maxillary
      first molar and second premolar were developed using computed tomography images
      of four patients. For each patient, an MSI surface model derived from micro
      computed tomography was placed at four different distances from the premolar PDL.
      Finite element analysis was conducted with mesial load on the MSI, increasing
      from 1 N to 4 N. Peak absolute compression stress (CS) was calculated at each 1 N
      step. Stepwise multiple regression modeling was conducted to explain compressive
      stress by proximity, load magnitude, and bone properties. RESULTS:: The multiple
      regression model explained 83.47% of the variation of CS and included all three
      factors: proximity, load magnitude, and bone properties. The model expected
      significant interaction between the bone properties and load magnitude, implying
      that strong bone properties could be associated with significant increases in CS
      at small increases in load. CONCLUSIONS:: To ensure the safety of adjacent roots,
      MSIs should be placed at least 1 mm from the roots. Assessment of alveolar bone
      properties is recommended when the use of MSI is intended, as some patients may
      present with strong bone properties and thereby a high risk of MSI-induced root
      resorption.

PMID- 30230378
TI  - Three-dimensional study of the upper airway in different skeletal Class II
      malocclusion patterns.
AB  - OBJECTIVES:: To characterize upper airway volume and morphology in patients with
      different skeletal patterns of Class II malocclusion compared to Class I.
      MATERIALS AND METHODS:: A total of 197 individuals who had cone-beam computed
      tomography were allocated into groups according to ANB, SNA, and SNB angles
      (Class I, Class II maxillary protrusion, Class II mandibular retrusion), each
      subdivided into hypodivergent, normal, and hyperdivergent. Nasopharynx (NP),
      oropharynx (OP), and hypopharynx (HP) were assessed with three-dimensional image
      reconstruction software. RESULTS:: Intergroup comparison did not detect
      significant differences in volume and morphology of NP, OP, and HP. The males
      displayed larger OP and HP volume than the females. Positive correlations between
      age and NP, OP, HP volume and between craniocervical angle and OP and HP volume
      were observed. Linear regression analysis detected a tendency for OP and HP
      volume to increase as maxillary and mandibular length increased. CONCLUSIONS::
      Upper airway volume and morphology were similar in different skeletal patterns of
      Class II malocclusion. Actual upper and lower jaw lengths were more closely
      related to upper airway volume and morphology than the angles that reflected
      their position relative to the cranial base.

PMID- 30230379
TI  - Genetic Counselor and Healthcare Interpreter Perspectives on the Role of
      Interpreters in Cancer Genetic Counseling.
AB  - Cancer genetic counseling (CGC) combines psychosocial counseling and genetic
      education provided by genetic counselors to patients and families who have a
      history of cancer and are considering or have undergone genetic testing for
      hereditary cancer syndromes. The quantity and complexity of information provided
      can be challenging for any patient, but is even more so for those with limited
      English proficiency (LEP). This exploratory study investigated healthcare
      interpreters' and genetic counselors' perspectives on the role of interpreters in
      providing care to LEP patients during CGC. Through a survey of 18 interpreters
      and conventional content analysis of semi-structured interviews with 11
      interpreters and 10 GCs at two California public hospitals, we found that: 1)
      interpreters viewed their role as patient advocate, cultural broker, and
      emotional support, not simply a conduit; 2) interpreters were challenged by
      remote interpretation, lack of genetic knowledge, and the emotional content of
      encounters; 3) interpreters and GCs held conflicting views of the value of
      counselors' limited Spanish knowledge; and 4) trust, the foundation of the
      interpreter-provider dyad, was often lacking. The challenges identified here may
      result in poor healthcare experiences and outcomes for LEP patients. As genomics
      becomes more widespread and more LEP patients encounter CGC, the role of
      healthcare interpreters in facilitating effective communication must be further
      defined in order to facilitate better working relationships between interpreters
      and genetic counselors, and optimal communication experiences for patients.

PMID- 30230380
TI  - The Retinal Oxygen Saturation Measured by Dual Wavelength Oximetry in Larger
      Retinal Vessels is Influenced by the Linear Velocity of the Blood.
AB  - PURPOSE: Dual wavelength retinal oximetry allows the quantification of oxygen
      saturation in the larger retinal vessels. However, the technique might be refined
      further by identifying factors that are responsible for the different oxygen
      saturations in first order arterioles from the same eye shortly after their
      branching from the central retinal artery. The purpose of the present study is to
      investigate whether these factors involve rheological characteristics in the
      studied vessels. MATERIALS AND METHODS: In fourty healthy persons the oxygen
      saturation was measured by dual wavelength oximetry and the blood flow by Doppler
      OCT in the upper and lower temporal and nasal arterioles and venules shortly
      after their branching from the central retinal artery and vein. The relationship
      of the measured oxygen saturations with age, vessel diameter, and blood linear
      velocity were assessed. RESULTS: The measured oxygen saturations were (mean+/-
      SD) 97.8% +/- 6.4% in the arterioles and 60.2% +/- 8.8% in the venules. For both
      the arterioles and the venules the measured oxygen saturation (Sm) correlated
      significantly with the linear velocity (v) of the blood in mm/s (Sm = 101.6
      0.28*v, p < 0.0001 for arterioles and Sm = 64.5-0.38*v, p = 0.002 for venules).
      After correction for the variation in linear velocity, the differences in
      saturation between first order branches from both arterioles and venules were
      significantly reduced and the standard deviation of the oxygen saturations were
      reduced to less than one third. CONCLUSIONS: Measurements of oxygen saturation in
      larger retinal arterioles and venules using dual wavelength oximetry can be
      improved by correcting for the influence of the linear velocity of the blood.

PMID- 30230381
TI  - Executive functions and health behaviors associated with the leading causes of
      death in the United States: A systematic review.
AB  - Research indicates that executive functioning may predict health behavior. This
      systematic review provides an overview of the relationship between domains of
      executive functioning and health behaviors associated with the leading causes of
      death in the United States. A total of 114 articles met the inclusion criteria
      (adult sample, published in English between 1990 and November 2016) and were
      reviewed and synthesized. Results indicated that although many studies had mixed
      findings, at least one executive function component was associated with every
      health behavior. Based on these results, health professionals should consider the
      role of executive functions in behavior change interventions.

PMID- 30230383
TI  - How are smartphones associated with adolescent materialism?
AB  - This study examined whether smartphone addiction predicted adolescent materialism
      and whether self-esteem mediated the relation between smartphone addiction and
      adolescent materialism. Moreover, this study tested whether this mediating
      process was moderated by student-student relationship. Our theoretical model was
      tested among 748 middle school students in China (mean age = 16.80, standard
      deviation = .73). The results indicated that smartphone addiction was positively
      related to adolescent materialism. Mediation analysis showed that self-esteem
      mediated this relation. Moderated mediation test further revealed that the
      mediated path was moderated by student-student relationship.

PMID- 30230382
TI  - Immunohistochemical demonstration of RECK protein and interleukin-6 in fetal
      membranes from singleton pregnancies with late preterm delivery, intact membranes
      and histological chorioamnionitis.
AB  - We investigated whether chorioamnionitis affects immunohistochemical
      demonstration of RECK protein and interleukin-6 (IL-6) expression in fetal
      placental membranes following late preterm delivery with intact membranes. Fetal
      membranes of 28 women with single pregnancy, preterm delivery and histologically
      documented chorioamnionitis at gestational age 34-366/7 weeks constituted the
      chorioamnionitis study group. The control group consisted of 28 fetal membranes
      from women with preterm deliveries at the same gestational age without
      histological chorioamnionitis. Immunohistochemistry was performed using
      monoclonal antibodies against RECK protein and IL-6. We found a statistically
      significant difference in RECK expression between the chorioamnionitis and
      control groups; however, we found no difference in IL-6 expression between the
      groups. We demonstrated that RECK expression is down-regulated in fetal membranes
      from pregnancies with spontaneous late preterm birth and intact membranes, which
      suggests its role in preterm parturition. Equal expression of IL-6 in fetal
      membranes of pregnancies with and without histological chorioamnionitis is an
      intriguing and unexpected observation that requires further investigation.

PMID- 30230384
TI  - A Review of the Cytokine IL-17 in Ocular Surface and Corneal Disease.
AB  - AIM: To investigate the role of interleukin-17 in ocular surface and corneal
      disease. Ocular surface and corneal disease is a leading cause of blindness and
      is an ongoing challenge for the public health sector to implement effective
      therapies. The majority of cells in corneal lesions are derived primarily from
      neutrophils that induce inflammatory events that lead to tissue damage. One of
      the key pro-inflammatory cytokines is IL-17, and it has been investigated in
      order to facilitate the understanding of the pathogenesis of ocular surface
      lesion development. METHOD: A review of the literature was performed through a
      systematic approach. RESULTS: IL-17 has been shown to exacerbate dry eye disease,
      viral and bacterial keratitis lesion severity, although it was found to be
      protective for Acanthamoeba. Antibodies developed to neutralize IL-17 have shown
      some promise in reducing the severity of some diseases. CONCLUSION: IL-17 plays a
      role in the pathogenesis of ocular surface and corneal disease and targeting this
      cytokine may provide a useful treatment option in the future.

PMID- 30230385
TI  - Invasive pulmonary aspergillosis in patients with solid tumours: risk factors and
      predictors of clinical outcomes.
AB  - BACKGROUND: The characteristics and management of invasive pulmonary
      aspergillosis (IPA) in patients with hematologic malignancies are well known, but
      IPA in patients with solid tumours is not well described. METHODS: We
      retrospectively reviewed all Aspergillus-positive cultures at a tertiary cancer
      center during 2004-2017. We identified 101 patients with IPA and solid tumours.
      We analyzed the association between clinical features and treatment and 12-week
      mortality and response to antifungal therapy. RESULTS: Fifty-one patients had
      lung cancer, 77 had underlying lung disease, 47 received chest radiation and 33
      had chronic obstructive pulmonary disease. Aspergillus fumigatus was the most
      common type isolated (71%); 68 patients (70%) were treated with voriconazole
      monotherapy. Independent risk factors for 12-week mortality included receiving
      steroids within 30 days of diagnosis (hazard ratio 2.2, 95% confidence interval
      [CI]: 1.1-4.6; p = .03) and chest radiotherapy (hazard ratio 2.6, 95% CI: 1.2
      5.5; p = .01). In multivariate analysis, a positive fungal stain was associated
      with lower odds of a successful response (odds ratio 0.2; 95% CI: 0.05-0.75; p =
      .02), whereas voriconazole treatment was associated with higher odds (odds ratio
      10.1; 95% CI: 2.1-48.5; p < .01). CONCLUSIONS: IPA should be considered in
      patients with solid tumours, particularly those with underlying lung disease. Key
      messages Invasive pulmonary aspergillosis should be considered in patients with
      solid tumours, particularly those with underlying lung disease, lung cancer and
      those who received chest radiotherapy. Most of the patients with invasive
      pulmonary aspergillosis and solid tumours presented with nonspecific symptoms and
      signs as well as nonspecific CT findings. Unlike patients with hematologic
      malignancies, fever and hemoptysis were not predominant symptoms and the
      classical halo sign and the air-crescent sign were not described. Independent
      risk factors for 12-week mortality included receiving steroids within 30 days of
      diagnosis and chest radiotherapy. In multivariate analysis, a positive fungal
      stain was associated with lower odds of a successful response to antifungal
      therapy, whereas voriconazole treatment was associated with higher odds.

PMID- 30230386
TI  - Brain targeting of chitosan-based diazepam mucoadhesive microemulsions via nasal
      route: formulation optimization, characterization, pharmacokinetic and
      pharmacodynamic evaluation.
AB  - OBJECTIVE: The aim of present investigation was to develop microemulsions (MEs)
      and mucoadhesive microemulsions (MME) of diazepam for brain uptake through nasal
      administration for the treatment of seizure emergency. SIGNIFICANCE: Status
      epilepticus (SE) is a medical emergency, requires intravenous administration of
      diazepam which requires hospitalization of patient. Initiation of therapy at home
      via nasal administration of diazepam could prevent the damage of brain due to
      delay of therapy initiation. METHODS: Diazepam MEs were prepared by phase
      titration method, optimized by using Box-Behnken design. The influence of
      independent variables oleic acid, surfactant mixture (tween 80:propylene glycol),
      and water on dependent variables size, flux, and zeta potential was investigated.
      Optimized MEs, MMEs, and Calmpose (i.v route) were evaluated for pharmacokinetic
      and pharmacodynamic studies on rats. RESULTS: MME2 composed of oleic acid (5),
      surfactant mixture (50), water (45), and chitosan (0.5) showed size of 96.45 nm,
      PDI 0.21 and zeta potential 13.52 mV. MME2 showed significantly high flux of
      846.96 +/- 34 ug/cm2/h and AUCbrain 1206.49 +/- 145.8. The drug targeting
      efficiency (314%) and direct nose-to-brain transport (68.1%) of MME2 were
      significantly high compared to Calmpose (i.v) and ME. The latency periods of
      minimal clonal seizures and generalized tonic-clonic seizures of MME2 was
      significantly increased (p < 0.0001) compared to drug solution and Calmpose
      (i.v). CONCLUSION: The brain uptake of diazepam from chitosan-based MMEs via
      nasal route is significantly high compared to i.v route.

PMID- 30230388
TI  - Dissolution or disintegration - substitution of dissolution by disintegration
      testing for a fixed dose combination product.
AB  - According to International Council for Harmonisation (ICH) guideline Q6A,
      dissolution testing can be replaced by disintegration testing if it can be shown
      that the active pharmaceutical ingredient is highly soluble and the formulation
      is rapidly releasing. In addition, a relationship between dissolution and
      disintegration has to be established. For a fixed-dose combination tablet of
      empagliflozin and linagliptin, this relationship was established by applying two
      different approaches. In the first approach, the extent to which the
      disintegration process of the film-coated tablets contributes to the release of
      the active ingredients was investigated. In the second approach, the mean
      disintegration times in a disintegration tester were correlated with the mean
      dissolution rates at a selected sampling time point. By correlating
      disintegration times in the dissolution vessel with the dissolution rate at
      selected sampling times it is demonstrated that the disintegration into primary
      particles is the rate limiting step for the dissolution process. A direct
      correlation of disintegration times in the disintegration tester with dissolution
      rate at a selected sampling time is established supporting a relationship between
      dissolution and disintegration testing for this type of formulation.
      Additionally, it could also be shown that the disintegration test method exhibits
      at least a similar discriminatory power compared to the proposed dissolution
      method. Based on a statistical approach and data from a bioavailability study, a
      clinical relevant specification for the disintegration time was established. All
      presented data support the replacement of dissolution by disintegration testing
      according to ICH Q6A for the selected fixed-dose combination product.

PMID- 30230389
TI  - Female fertility in the cancer setting: availability and quality of online health
      information.
AB  - As cancer survival rates continue to increase, so does the relevance of starting
      or expanding a family after cancer, impacting quality of life. However, the
      option of fertility preservation is not always addressed by physicians before
      treatment. In the meanwhile, many patients look for health information online.
      Although potentially helpful in the decision-making process, the Internet could
      also have adverse effects for this vulnerable patient group when information is
      incorrect. We aimed to assess the availability and quality of information on
      female oncofertility on websites of (inter)national oncology, fertility and
      oncofertility organizations. Availability was identified using an original
      checklist. Quality was measured by reliability (DISCERN and LIDA instruments),
      usability (LIDA instrument), and readability (Flesch Kincaid Grade Level test).
      Of all investigated websites, 52% contained information on oncofertility, with
      32% containing a stand-alone page. Of those sites, the amount of treatment
      options covered were equivalent between specialty sites and general fertility and
      oncology sites (p = 0.07). The quality of information on treatment choices was
      the highest for oncofertility websites. Reliability and usability did not differ
      significantly between websites. No websites evaluated were at the recommended 7th
      8th grade reading level. Availability and quality should be improved, and high
      quality resources are recommended by physicians.

PMID- 30230387
TI  - Synthesis and structure-activity relationships of 2- and/or 4-halogenated 13beta-
      and 13alpha-estrone derivatives as enzyme inhibitors of estrogen biosynthesis.
AB  - Ring A halogenated 13alpha-, 13beta-, and 17-deoxy-13alpha-estrone derivatives
      were synthesised with N-halosuccinimides as electrophile triggers. Substitutions
      occurred at positions C-2 and/or C-4. The potential inhibitory action of the
      halogenated estrones on human aromatase, steroid sulfatase, or 17beta
      hydroxysteroid dehydrogenase 1 activity was investigated via in vitro
      radiosubstrate incubation. Potent submicromolar or low micromolar inhibitors were
      identified with occasional dual or multiple inhibitory properties. Valuable
      structure-activity relationships were established from the comparison of the
      inhibitory data obtained. Kinetic experiments performed with selected compounds
      revealed competitive reversible inhibition mechanisms against 17beta
      hydroxysteroid dehydrogenase 1 and competitive irreversible manner in the
      inhibition of the steroid sulfatase enzyme.

PMID- 30230390
TI  - SCC4 cell monolayers as an alternative sublingual barrier model: influence of
      nanoencapsulation on carvedilol transport.
AB  - OBJECTIVE: To evaluate, for the first time, the use of SCC4 cell monolayers as an
      alternative sublingual barrier model and study the influence of nanoencapsulation
      on carvedilol transport across SCC4 cell monolayers. SIGNIFICANCE: The sublingual
      cavity is an interesting route for administration of drugs with limited oral
      bioavailability due to hepatic first pass metabolism. By this route, the drug is
      directly absorbed into blood circulation. In this sense, mucoadhesive carvedilol
      loaded nanocapsules (CAR-NC) were previously proposed for the administration of
      this drug by sublingual route. Carvedilol is used for cardiovascular diseases and
      suffers metabolism in liver when orally administrated. Nanoencapsulation of
      carvedilol controlled its permeation across porcine sublingual mucosa. METHODS:
      Carvedilol-loaded cationic nanocapsules were prepared by interfacial deposition
      of a preformed polymer. Drug permeation studies were carried out in Transwell(r)
      inserts. The integrity of cell monolayers after the drug transport was assessed
      by transepithelial electric resistance. Compatibility of the CAR-NC with the SCC4
      cells was evaluated by the Sulforhodamine B assay. RESULTS: The drug permeated
      the cell monolayer by a controlled way when nanoencapsulated and this profile had
      a linear relation with those observed in porcine sublingual mucosa. The integrity
      of the cell monolayer was maintained after drug permeation and CAR-NC was no
      cytotoxic to SCC4 cells. CONCLUSION: Nanoencapsulated carvedilol permeated by a
      controlled and safe way by SCC4 cell monolayer. SCC4 cells monolayers may be used
      as in vitro model for sublingual drug transport studies in the development of
      novel formulations.

PMID- 30230391
TI  - Subjective social status and health: Multidisciplinary explanations and
      methodological challenges.
AB  - Since the early 2000s, evidence has been accumulating that subjective social
      status - a person's sense of their own position on the social ladder - affects
      health above and beyond objective socioeconomic status. To date, however, little
      is known about how these distinct health effects of subjective social status can
      be explained. This article narratively reviews different explanatory approaches
      and key methodological challenges, backed up by empirical findings and
      supplemented by the authors' own reflections. Both social-psychological and
      psychoneurobiological explanations can make a theoretically plausible
      contribution to explaining the subjective social status-health relationship.
      Experimental and panel designs appear promising for addressing important
      methodological challenges in this strand of research.

PMID- 30230392
TI  - Potentially avoidable inter-hospital transfer for gynaecology consultation at a
      tertiary care centre: a retrospective study.
AB  - Inter-hospital transfers for consultation are common and costly in the USA. Our
      objective was to evaluate the inter-hospital transfers between the emergency
      departments (ED) for a gynaecology consultation and to identify markers for
      potentially avoidable transfers. We performed a retrospective chart review of all
      transfers accepted by a tertiary care hospital gynaecology service via the ED
      over two years. Our primary outcome was the designation of the transfer as
      'potentially avoidable', defined as a patient discharged home directly from the
      ED, with no workup or treatment prior to their discharge. The Chi-square tests
      were used to assess what patient characteristics and medical diagnoses are
      associated with potentially avoidable transfers. Of 156 patients meeting the
      inclusion criteria, a total of 38 (24.4%) were potentially avoidable transfers.
      Women with potentially avoidable transfers were more likely to be pregnant than
      those whose transfers were necessary (63.2% vs. 40.7% p = .02), and more likely
      to specifically have a pregnancy of unknown location (PUL) or a complete abortion
      (p < .01).

PMID- 30230393
TI  - Risk of ovarian torsion is reduced in GnRH agonist triggered freeze-all cycles: a
      retrospective cohort study.
AB  - Ovarian torsion (OT) in IVF is rare, however, the consequences are significant,
      which include ovariotomy. In the present study, it was aimed for the first time
      to compare the incidence of OT between hCG triggered cycles with ICSI and fresh
      transfer and GnRH-agonist triggered cycles with the ICSI-freeze-all and frozen
      embryo transfer (FET). In total, 15,577 ICSI cycles performed between 2001 and
      2016 were categorised into two groups (Group 1, n: 9978): cycles with controlled
      ovarian stimulation (COS) and hCG-triggered (Group 2, n: 5599) and COS, with GnRH
      agonist only triggered and freeze-all. Thirteen patients (0.13%) were diagnosed
      with OT and corrected by laparoscopy (12) and laparotomy (1) in Group 1. One
      patient (0.018%) was diagnosed with OT and corrected by laparotomy in Group 2
      (Group 1 vs. Group 2, p = .049). The incidence of severe ovarian hyperstimulation
      syndrome (OHSS) was 2.4% in Group 1 and 0.05% in Group 2 (p < .001). The use of
      freeze-all with GnRH agonist trigger in ART significantly reduced the incidence
      of OT and concomitantly OHSS, with no effect on the reproductive outcome. Impact
      Statement What is already known on this subject? Adnexal ovarian torsion (OT) is
      a well-known gynaecological event that constitutes a surgical emergency. Assisted
      reproduction technologies (ART) may result in ovarian conditions that predispose
      patients to ovarian hyperstimulation syndrome (OHSS) and torsion. What the
      results of this study add? The combined use of GnRH agonist trigger for final
      oocyte maturation after OS with freeze-all and frozen embryo transfer (FET)
      significantly reduces the incidence of OT, as well as OHSS. What the implications
      are of these findings for clinical practice and/or further research? The
      treatment strategy of GnRH agonist trigger with freeze-all significantly reduces
      the risks of adverse complications.

PMID- 30230394
TI  - The use of colposcopic punch biopsy in the management of abnormal cervical
      cytology: a 5-year retrospective audit.
AB  - The aim of this study was to determine the accuracy of colposcopic punch biopsy
      to detect cervical epithelial neoplasia (CIN) II + in patients with abnormal
      cervical cytology and the major colposcopic findings in patients who underwent a
      loop electrosurgical excision procedure (LEEP), subsequently. A total of 231
      patients with abnormal cervical cytology who underwent a colposcopy guided
      cervical biopsy and subsequent LEEP were analysed. The mean age was 33.4 +/- 8.7
      years. CIN II + rate on LEEP pathology was significantly higher in patients with
      high-grade cytology, compared to those with a low-grade cytology (92 vs. 55%, p <
      .0001). CIN II + was found in 80, 98 and 100% of colpocopic biopsies of patients
      with LSIL, HSIL and AGC, respectively. The overall concordance rate between a
      colposcopic biopsy and LEEP was 41% with a kappa coefficient. The overall
      underestimation of CIN II + was 10.5%. On a patient-based analysis, the
      sensitivity, specificity, PPV and NPV of colposcopic biopsy were 89.4, 47.1, 79.5
      and 66%, respectively. More than two cervical biopsies had 100% sensitivity for
      CIN II + on LEEP pathology. The specificity and PPV decreased with increasing
      number of cervical biopsies. A see-and-treat strategy may be considered for high
      grade cytologies. Patients with a low-grade cytology should be managed with more
      than two colposcopic biopsies.

PMID- 30230395
TI  - Nationwide content analysis of undergraduate obstetrics and gynaecology clinical
      curricula in Turkish medical schools.
AB  - The aim was to perform a document content analysis of the subject titles in the
      undergraduate obstetrics and gynaecology (OG) curricula in Turkish medical
      schools regarding the National Core Curriculum revised in 2014 (NCC-2014). Two
      mini-focus group discussions with four voluntary OG faculty members in each
      session and one of the authors as the moderator were employed within a 1-week
      time frame to identify the primary (n = 36) and secondary (n = 15) NCC-2014 OG
      titles that were then compared for the alignment with the curricula of the
      various medical schools published on their website. The internet search and data
      analyses were each completed within 3 months. Overall, about 80% and 23% of
      primary and secondary OG topics were present in 54 medical schools, respectively.
      Teaching sessions on high-risk pregnancy and ovarian cancer were present in all
      of the curricula. Chromosomal disorders (11 schools), candidiasis/vaginal
      discharge (13 schools) and female sexual dysfunction (15 schools) were the least
      represented primary topics. None of the curricula had a title on neural tube
      defects or oncological emergencies. Obesity (one school), iron deficiency anaemia
      (four schools), genitourinary trauma (four schools) and domestic violence (four
      schools) were among the underrepresented secondary subject titles. This
      nationwide analysis revealed deficiencies in undergraduate OG core curricular
      content of the medical schools.

PMID- 30230396
TI  - Conservative management of huge spontaneous onset retroperitoneal haematoma
      following normal vaginal delivery.

PMID- 30230397
TI  - Completion surgery after chemoradiotherapy for cervical cancer - is there a role?
      UK Cancer Centre experience of hysterectomy post chemo-radiotherapy treatment for
      cervical cancer.
AB  - The standard treatment for locally advanced cervical cancer is chemo
      radiotherapy. The presence of the residual disease after treatment is directly
      related to the relapse risk and to poor survival. There is a lack of consensus on
      the role of a subsequent surgery due to morbidity concerns. Oncological and peri
      operative outcomes of completion surgery for cervical cancer were reviewed by
      retrospective descriptive analysis of the eligible cases between March 2012 and
      March 2016. Fifteen women were identified. Ten (66.7%) had a residual tumour on
      their post-treatment MRI. Surgical histology indicated a residual cancer in
      26.7%. There were three distant recurrences. Bowel and urinary complications were
      most commonly reported. Offering surgery to women with a residual cervical tumour
      found on MRI after chemo-radiation is beneficial, despite clear risks from the
      dual-modality treatment. A less radical surgery is preferable. An MRI has a
      reasonable negative predictive value, but this study has highlighted the need to
      further examine the role of MRI in predicting the residual disease and
      recurrence. Impact statement What is already known on this subject? The standard
      treatment for locally advanced cervical cancer is chemo-radiotherapy. The
      presence of residual disease after treatment is directly related to the relapse
      risk and poor survival. There is a lack of consensus on the role of a subsequent
      surgery due to morbidity concerns. The current evidence in the UK is limited, but
      across the world it appears that surgery can be beneficial for patients with
      incomplete chemo-radiotherapy, for certain histological subtypes of cervical
      cancer or for bulky residual disease. What do the results of this study add? The
      mode of surgery is more debateable, and this study concludes that both the
      laparoscopic and open surgeries are acceptable, but that radical surgery should
      be avoided as this contributes to a significant post-operative morbidity. This
      study explores the role of MRI imaging in predicting the residual disease and
      cervical cancer recurrence, concluding that a negative MRI post-chemoradiotherapy
      has a good negative predictive value for squamous cell cervical cancer, but
      otherwise can be unreliable. What are the implications of these findings for
      clinical practice and/or further research? An additional explored role of the MRI
      in predicting a recurrence in a larger cohort will be required, and it is likely
      that an additional assessment with PET-CT scanning will improve specificity.

PMID- 30230398
TI  - Genital tuberculosis in a post-menopausal Caucasian woman: a case report.

PMID- 30230399
TI  - Randomized crossover feasibility trial of helminthic Trichuris suis ova versus
      placebo for repetitive behaviors in adult autism spectrum disorder.
AB  - OBJECTIVES: Inflammatory mechanisms are implicated in the aetiology of autism
      spectrum disorder (ASD), and use of the immunomodulator Trichuris suis Ova (TSO)
      is a novel treatment approach. This pilot study determined the effect sizes for
      TSO versus placebo on repetitive behaviours, irritability and global functioning
      in adults with ASD. METHODS: A 28-week double-blind, randomised two-period
      crossover study of TSO versus placebo in ten ASD adults, aged 17-35, was
      completed, with a 4-week washout between each 12-week period at Montefiore
      Medical Center, Albert Einstein College of Medicine. Subjects with ASD, history
      of seasonal, medication or food allergies, Y-BOCS >=6 and IQ >=70 received 2,500
      TSO ova or matching placebo every 2 weeks of each 12-week period. RESULTS: Large
      effect sizes for improvement in repetitive behaviours (d = 1.0), restricted
      interests (d = 0.82), rigidity (d = 0.79) and irritability (d = 0.78) were
      observed after 12 weeks of treatment. No changes were observed in the social
      communication domain. Differences between treatment groups did not reach
      statistical significance. TSO had only minimal, non-serious side effects.
      CONCLUSIONS: This proof-of-concept study demonstrates the feasibility of TSO for
      the treatment of ASD, including a favourable safety profile, and moderate to
      large effect sizes for reducing repetitive behaviours and irritability.
      Clinicaltrials.gov: NCT01040221.

PMID- 30230401
TI  - Cognitive predictors of parent-rated inattention in very preterm children: The
      role of working memory and processing speed.
AB  - Inattention is one of the most common neurobehavioral problems following very
      preterm birth. Attention problems can persist into adulthood and are associated
      with negative socio-emotional and educational outcomes. This study aimed to
      determine whether the cognitive processes associated with inattention differ
      between term-born and very preterm children. Sixty-five children born very
      preterm (<33+0 weeks' gestation) aged 8-11 years were recruited alongside 48 term
      born controls (?37 20 +0 weeks' gestation). Both groups included children with a
      wide spectrum of parent-rated inattention (above average attention to severe
      inattention) measured as a continuous dimension using the Strengths and
      Weaknesses of ADHD and Normal-Behavior (SWAN) scale. The children completed tests
      to assess basic cognitive processes and executive function. A hierarchical
      multiple regression analysis was implemented to assess which neurocognitive
      processes explained variance in parent-rated inattention and whether these
      differed between preterm and term-born children. In both groups, poorer verbal
      and visuospatial short-term memory and poorer visuospatial working memory
      independently explained variance in parent-rated inattention. Slower motor
      processing speed explained variance in inattention among very preterm children
      only. The cognitive mechanisms associated with parent-rated inattention were
      predominantly overlapping between groups, but relationships between motor
      processing speed and inattention were unique to very preterm children. These
      associations may reflect risk factors for inattention in term and very preterm
      children. Future research should assess the efficacy of these cognitive processes
      as potential targets for intervention.

PMID- 30230400
TI  - Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple
      sclerosis.
AB  - BACKGROUND: Cognitive impairment (CI) profoundly impacts quality of life for
      patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in
      gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem
      pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM
      pathology is subtle and difficult to detect using conventional T1- and T2
      weighted magnetic resonance imaging (MRI). There is a need for high-resolution,
      clinically accessible imaging techniques that probe molecular changes in GM.
      OBJECTIVE: To study cortical GM pathology related to CI in MS using glutamate
      sensitive chemical exchange saturation transfer (GluCEST) MRI at 7.0 Tesla (7T).
      METHODS: A total of 20 patients with relapsing-remitting MS and 20 healthy
      controls underwent cognitive testing, anatomical imaging, and GluCEST imaging.
      Glutamate-sensitive image contrast was quantified for cortical GM, compared
      between cohorts, and correlated with clinical measures of CI. RESULTS AND
      CONCLUSION: Glutamate-sensitive contrast was significantly increased in the
      prefrontal cortex of MS patients with accumulated disability ( p < 0.05). In
      addition, glutamate-sensitive contrast in the prefrontal cortex was significantly
      correlated with symbol digit modality test ( rS = -0.814) and choice reaction
      time ( rS = 0.772) scores in patients ( p < 0.05), suggesting that GluCEST MRI
      may have utility as a marker for GM pathology and CI.

PMID- 30230402
TI  - The effects of fish oil omega-3 fatty acid supplementation on mental health
      parameters and metabolic status of patients with polycystic ovary syndrome: a
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: This study was conducted to evaluate the effects of fish oil omega-3
      fatty acid supplementation on mental health parameters and metabolic status of
      women with polycystic ovary syndrome (PCOS). METHODS: This randomized double
      blind, placebo-controlled trial was conducted on 60 women with PCOS, aged 18-40
      years old. Participants were randomly assigned into two groups to receive either
      2 * 1000 mg/day fish oil omega-3 fatty acid (n = 30) or placebo (n = 30) after
      lunch for 12 weeks. Metabolic profiles were quantified at baseline and after the
      12-week intervention. RESULTS: Compared with the placebo, omega-3 fatty acid
      intake led to a significant improvement in Beck Depression Inventory [beta
      (difference in the mean outcomes measures between treatment groups after
      intervention) -1.05; 95% CI: -1.84, -0.26; p = .01], general health questionnaire
      (beta -1.68; 95% CI: -3.12, -0.24; p = .02) and depression anxiety and stress
      scale (beta -2.03; 95% CI: -3.60, -0.46; p = .01). Omega-3 fatty acid
      supplementation significantly decreased serum insulin levels (beta -2.09 uIU/mL;
      95% CI: -3.77, -0.41; p = .01), homeostasis model of assessment-insulin
      resistance (beta -0.74; 95% CI: -1.13, -0.34; p < .001), total testosterone (beta
      -0.23 ng/mL; 95% CI: -0.39, -0.06; p = .03) and hirsutism (beta -0.75; 95% CI: 
      1.17, -0.33; p = .001), and significantly increased the quantitative insulin
      sensitivity check index (beta 0.01; 95% CI: 0.003, 0.02; p = .008) compared with
      the placebo. Additionally, omega-3 fatty acid intake resulted in a significant
      decrease in high sensitivity C-reactive protein (beta -1.46 mg/L; 95% CI: -2.16, 
      0.75; p < .001) and malondialdehyde (beta -0.28 umol/L; 95% CI: -0.52, -0.05; p =
      .03); also significant rises in plasma total glutathione (beta 59.09 umol/L; 95%
      CI: 7.07, 111.11; p = .02) was observed compared with the placebo. Omega-3 fatty
      acid supplementation did not change other metabolic parameters. CONCLUSION:
      Overall, omega-3 fatty acid supplementation for 12 weeks to patients with PCOS
      had beneficial effects on mental health parameters, insulin metabolism, total
      testosterone, hirsutism and few inflammatory markers and oxidative stress.

PMID- 30230403
TI  - A feasibility study on identifying drinking-related contents in Facebook through
      mining heterogeneous data.
AB  - Binge drinking is a severe health problem faced by many US colleges and
      universities. College students often post drinking-related text and images on
      social media, portraying their alcohol use as socially desirable. In this
      project, we investigated the feasibility of mining the heterogeneous data (e.g.
      text, images, and videos) on Facebook to identify drinking-related contents. We
      manually annotated 4266 posts during 21 October 2011 and 3 November 2014 from
      "I'm Shmacked" group on Facebook, where 511 posts were drinking-related. Our
      machine learning models show that by combining heterogeneous data types, we were
      able to identify drinking-related posts with an F1-score of 0.81. Prediction
      models built on text data were more reliable compared to those built on image and
      video data for predicting drinking-related contents. As the first step of our
      efforts in this direction, this feasibility study showed promise toward
      unleashing the potential of mining social media to identify students who binge
      drink.

PMID- 30230404
TI  - Impaired copper transport in schizophrenia results in a copper-deficient brain
      state: a new side to the dysbindin story.
AB  - Several schizophrenia brain regions exhibit decreased dysbindin. Dysbindin
      modulates copper transport crucial for myelination, monoamine metabolism, and
      cellular homeostasis. Schizophrenia patients (SZP) exhibit increased plasma
      copper, while copper-decreasing agents produce schizophrenia-like behavioral and
      pathological abnormalities. Therefore, we sought to determine dysbindin and
      copper transporter protein expression and copper content in SZP. We studied the
      copper-rich substantia nigra (SN) using Western blot and inductively-coupled
      plasma mass spectrometry. We characterized specific protein domains of copper
      transporters ATP7A, CTR1, ATP7B, and dysbindin isoforms 1A and 1B/C in SZP (n =
      15) and matched controls (n = 11), and SN copper content in SZP (n = 14) and
      matched controls (n = 11). As a preliminary investigation, we compared medicated
      (ON; n = 11) versus unmedicated SZP (OFF; n = 4). SZP exhibited increased C
      terminus, but not N-terminus, ATP7A. SZP expressed less transmembrane CTR1 and
      dysbindin 1B/C than controls. ON exhibited increased C-terminus ATP7A protein
      versus controls. OFF exhibited less N-terminus ATP7A protein than controls and
      ON, suggesting medication-induced rescue of the ATP7A N-terminus. SZP exhibited
      less SN copper content than controls. These results provide the first evidence of
      disrupted copper transport in schizophrenia SN that appears to result in a copper
      deficient state. Furthermore, copper homeostasis may be modulated by specific
      dysbindin isoforms and antipsychotic treatment.

PMID- 30230405
TI  - Editorial.

PMID- 30230406
TI  - Effects of agomelatine on behaviour, circadian expression of period 1 and period
      2 clock genes and neuroplastic markers in the predator scent stress rat model of
      PTSD.
AB  - OBJECTIVES: The therapeutic value of the antidepressant agomelatine in the
      aftermath of traumatic experience and early post-reminder has been questioned.
      Herein, agomelatine, its vehicle or melatonin agonist were administered either
      acutely 1 h post-stressor or repeatedly (7 days) after early post-reminder in a
      post-traumatic stress rat model (PSS) using the scent of predator urine. METHODS:
      Behavioural responses, and brain molecular and morphological changes were
      evaluated after each treatment procedure in PSS-exposed and unexposed rats.
      RESULTS: When administered immediately after PSS, agomelatine induced a
      significant reduction of anxiety-like behaviour as assessed in the elevated-plus
      maze and acoustic startle response at 8 days post-administration. Concomitantly,
      agomelatine significantly decreased Per1/Per2 expression in the CA1/CA3 areas,
      suprachiasmatic nucleus and basolateral amygdala, thereby partially restoring
      genes expression overregulated by PSS. Agomelatine further significantly
      increased cell growth and facilitated dendritic growth and arbour in dentate
      gyrus (DG) granule and apical CA1 cells and upregulated brain-derived
      neurotrophic factor protein in the DG and cortex III versus vehicle. When
      administered early post-reminder over 7 days before testing, agomelatine was
      ineffective on behavioural responses pattern, molecular and morphological changes
      induced by PSS. CONCLUSIONS: These findings suggest that agomelatine may be a
      potential agent in the acute aftermath of traumatic stress exposure.

PMID- 30230407
TI  - Physician Attitudes Toward Homosexuality and HIV: The PATHH-III Survey.
AB  - PURPOSE: The aims of this study were (1) to evaluate current physician attitudes
      toward homosexuality and homosexual, transgender, and HIV-positive individuals
      and (2) to compare current attitudes of those from prior surveys of the same
      population, the San Diego County medical community. METHODS: An online survey was
      conducted during November-December 2017 to assess general attitudes toward
      homosexuality and medically focused items that addressed homosexual orientation,
      transgender identity, and HIV. Responses were weighted for nonresponse.
      Predictors of stigma were assessed using generalized linear models. Trends across
      three surveys of the same population in 1982, 1999, and 2017 using common items
      were assessed using unweighted responses. RESULTS: Of 4418 eligible physicians,
      491 (11.1%) responded (median age 55 years, 38% female and 8.7% gay or bisexual).
      Regarding admission to medical school, 1% opposed admitting a homosexual
      applicant, 2% a transgender applicant, and 5% an HIV-positive applicant.
      Regarding consultative referral to a pediatrician, 3% would discontinue referral
      to a homosexual pediatrician, 5% to a transgender pediatrician, and 10% to an HIV
      positive pediatrician. Regarding discomfort treating patients, 7% reported
      discomfort treating homosexual patients, 22% transgender patients, and 13% HIV
      positive patients. Earlier year of graduation from medical school, male gender,
      and heterosexual orientation were significant predictors of stigma-associated
      responses. Compared with the results from surveys in 1982 and 1999, the current
      results suggest substantively less stigma associated with homosexuality and HIV.
      CONCLUSION: There have been substantive declines over a 35-year period in the
      prevalence of stigmatizing attitudes toward sexual minorities and HIV-positive
      people among physician respondents in three survey waves of the San Diego County
      medical community.

PMID- 30230408
TI  - The class imbalance problem detecting adverse drug reactions in electronic health
      records.
AB  - This work focuses on adverse drug reaction extraction tackling the class
      imbalance problem. Adverse drug reactions are infrequent events in electronic
      health records, nevertheless, it is compulsory to get them documented. Text
      mining techniques can help to retrieve this kind of valuable information from
      text. The class imbalance was tackled using different sampling methods, cost
      sensitive learning, ensemble learning and one-class classification and the Random
      Forest classifier was used. The adverse drug reaction extraction model was
      inferred from a dataset that comprises real electronic health records with an
      imbalance ratio of 1:222, this means that for each drug-disease pair that is an
      adverse drug reaction, there are approximately 222 that are not adverse drug
      reactions. The application of a sampling technique before using cost-sensitive
      learning offered the best result. On the test set, the f-measure was 0.121 for
      the minority class and 0.996 for the majority class.

PMID- 30230410
TI  - A qualitative study exploring the experiences of mindfulness training in people
      with acquired brain injury.
AB  - Recently, there has been increased interest in using mindfulness-based
      interventions (MBIs) in brain injury rehabilitation. However, no previous
      qualitative research has explored the experiences of individuals with acquired
      brain injury (ABI) receiving these interventions. The present study, therefore,
      aimed to explore how individuals with ABI make sense of their experiences of
      learning mindfulness skills. Six focus group interviews were conducted with 14
      participants with ABI after they had completed an eight-week mindfulness group.
      The group interviews were transcribed verbatim and analysed using Interpretative
      Phenomenological Analysis (IPA). Four themes provided in-depth information about
      participants' lived experiences of mindfulness training and being in the group;
      "Developmental learning process", "Group as a supportive environment for
      learning", "Increased awareness" and "Benefits of mindfulness". The accounts
      capture participants' journeys through the process of learning mindfulness skills
      and implementing them in their everyday lives. The findings also suggested that
      most participants considered mindfulness beneficial in terms of helping them to
      cope with the emotional and cognitive consequences of ABI.

PMID- 30230409
TI  - Effect of oral misoprostol, alone or in combination with aglepristone, on mid
      term pregnancy termination in cats.
AB  - Objectives This study aimed to determine the efficacy and safety of oral
      misoprostol (MIS) administration in the induction of mid-term pregnancy
      termination in cats. Methods Twenty-eight cats that were pregnant for 30-40 days
      were allocated to four groups. The aglepristone (AGL) group (n = 7) received 10
      mg/kg SC aglepristone q24h for two consecutive days. In the AGL+MIS group (n =
      7), AGL (as administered in the AGL group) and MIS (200 ug/cat PO q12h until the
      start of abortion) were administered. The MIS200 (n = 7) and MIS400 groups (n =
      7) received MIS (200 or 400 ug/cat misoprostol, respectively) alone PO q12h until
      the start of abortion. Blood samples were collected at the start of treatment
      (d0), 4 days after the start of treatment (d4) and on the day of complete
      abortion/end of administration (dA/d7). Results The efficacy of the treatment was
      71.4% in the AGL group, 100% in the AGL+MIS group, 0% in MIS200 group and 57.4%
      in MIS400 group ( P = 0.004). No significance was found in relation to the
      interval from treatment to the start/end of abortion and the duration of abortion
      in all groups. The most observed side effect was vomiting in both groups
      administered MIS, particularly in the MIS400 group (56.7%). Progesterone (P4)
      concentrations were reduced during the abortion, but not to basal levels, in all
      groups. P4 concentrations were significantly lower at dA/d7 in the MIS400 group
      compared with the AGL and AGL+MIS groups ( P = 0.002). Conclusions and relevance
      The results obtained from this study showed that low doses of MIS do not induce
      abortions in cats but increase the effect of AGL. Although higher doses could
      terminate pregnancies, this also causes intense unwanted side effects. Therefore,
      the use of MIS alone as an abortifacient in cats is not recommended. For mid-term
      pregnancy termination in cats, the combination of misoprostol and aglepristone
      provides a more effective abortifacient than using either of them alone.

PMID- 30230411
TI  - Volumetric voxelwise apparent diffusion coefficient histogram analysis for
      differentiation of the fourth ventricular tumors.
AB  - PURPOSE: We applied voxelwise apparent diffusion coefficient (ADC) histogram
      analysis in addition to structural magnetic resonance imaging (MRI) findings and
      patients' age for differentiation of intraaxial posterior fossa tumors involving
      the fourth ventricle. PARTICIPANTS AND METHODS: Pretreatment MRIs of 74 patients
      with intraaxial brain neoplasm involving the fourth ventricle, from January 1,
      2004 to December 31, 2015, were reviewed. The tumor solid components were
      segmented and voxelwise ADC histogram variables were determined. Histogram-driven
      variables, structural MRI findings, and patient age were combined to devise a
      differential diagnosis algorithm. RESULTS: The most common neoplasms were
      ependymomas ( n = 21), medulloblastoma ( n = 17), and pilocytic astrocytomas ( n
      = 13). Medulloblastomas followed by atypical teratoid/rhabdoid tumors had the
      lowest ADC histogram percentile values; whereas pilocytic astrocytomas and
      choroid plexus papillomas had the highest ADC histogram percentile values. In a
      multivariable multinominal regression analysis, the ADC 10th percentile value
      from voxelwise histogram was the only independent predictor of tumor type ( p <
      0.001). In separate binary logistic regression analyses, the 10th percentile ADC
      value, tumor morphology, enhancement pattern, extension into Luschka/Magendie
      foramina, and patient age were predictors of different tumor types. Combining
      these variables, we devised a stepwise diagnostic model yielding 71% to 82%
      sensitivity, 91% to 95% specificity, 75% to 78% positive predictive value, and
      89% to 95% negative predictive value for differentiation of ependymoma,
      medulloblastoma, and pilocytic astrocytoma. CONCLUSION: We have shown how the
      addition of quantitative voxelwise ADC histogram analysis of the tumor solid
      component to structural findings and patient age can help with accurate
      differentiation of intraaxial posterior fossa neoplasms involving the fourth
      ventricle based on pretreatment MRI.

PMID- 30230414
TI  - An accessible and efficient autism screening method for behavioural data and
      predictive analyses.
AB  - Autism spectrum disorder is associated with significant healthcare costs, and
      early diagnosis can substantially reduce these. Unfortunately, waiting times for
      an autism spectrum disorder diagnosis are lengthy due to the fact that current
      diagnostic procedures are time-consuming and not cost-effective. Overall, the
      economic impact of autism and the increase in the number of autism spectrum
      disorder cases across the world reveal an urgent need for the development of
      easily implemented and effective screening methods. This article proposes a new
      mobile application to overcome the problem by offering users and the health
      community a friendly, time-efficient and accessible mobile-based autism spectrum
      disorder screening tool called ASDTests. The proposed ASDTests app can be used by
      health professionals to assist their practice or to inform individuals whether
      they should pursue formal clinical diagnosis. Unlike existing autism screening
      apps being tested, the proposed app covers a larger audience since it contains
      four different tests, one each for toddlers, children, adolescents and adults as
      well as being available in 11 different languages. More importantly, the proposed
      app is a vital tool for data collection related to autism spectrum disorder for
      toddlers, children, adolescent and adults since initially over 1400 instances of
      cases and controls have been collected. Feature and predictive analyses
      demonstrate small groups of autistic traits improving the efficiency and accuracy
      of screening processes. In addition, classifiers derived using machine learning
      algorithms report promising results with respect to sensitivity, specificity and
      accuracy rates.

PMID- 30230412
TI  - Predictors of improvement in an open-trial multisite evaluation of emotion
      regulation group therapy.
AB  - Emotion regulation group therapy (ERGT) is a novel treatment specifically
      targeting deliberate non-suicidal self-harm (DSH) in individuals with borderline
      personality disorder (BPD). Identifying robust predictors of positive response to
      ERGT could aid clinicians in treatment selection; however, to date, only one such
      study has been conducted. Thus, we aimed to replicate previously identified
      predictors of treatment response to ERGT by investigating demographic, clinical,
      and diagnostic predictors in 95 women with BPD or subclinical BPD who had
      participated in an open-trial evaluation of ERGT. Outcomes evaluated were
      frequency of DSH and emotion dysregulation. Assessments were conducted at
      pretreatment, post-treatment, and 6-month follow-up. Multilevel mixed linear
      models and multilevel negative binomial generalized estimated equations were used
      to identify significant interactions between the predictors and outcomes. We
      found that greater pretreatment DSH frequency was associated with greater
      improvements in DSH during treatment (b = 0.998, SE = 0.00, p = 0.03) and follow
      up (b = 0.997, SE = 0.00, p < 0.01) and that greater BPD severity was associated
      with greater improvements in DSH during treatment (b = 0.84, SE = 0.06, p = 0.02)
      and in emotion dysregulation at follow-up (b = -3.05, SE = 1.47, p = 0.04). Co
      occurring disorders were associated with poorer treatment response during follow
      up. Results were generally consistent with a previous study of the predictors of
      response to ERGT. The findings provide further support for the utility of this
      treatment across a range of BPD patients, including patients with severe DSH and
      BPD.

PMID- 30230413
TI  - Clinical and genetic analysis of distal renal tubular acidosis in three Chinese
      children.
AB  - OBJECTIVE: Primary distal renal tubular acidosis (dRTA) is a rare genetic disease
      characterized by distal tubular dysfunction leading to metabolic acidosis and
      alkaline urine. Growth retardation is a major concern in these children. The
      disease is caused by defects in at least three genes (SLC4A1, ATP6V0A4, and
      ATP6V1B1) involved in urinary distal acidification. Several series of dRTA
      patients from different ethnic backgrounds have been genetically studied, but
      genetic studies regarding Chinese population is rare. Our aim was to investigate
      the clinical features and genetic basis of primary dRTA in Chinese children.
      METHODS: Three unrelated patients with dRTA participated in our study. Next
      generation sequencing was performed, and the findings were validated using the
      Sanger sequencing method. RESULTS: All patients exhibited hyperchloraemic
      metabolic acidosis, abnormally high urine pH, hypokalemia, and nephrocalcinosis.
      Growth retardation was observed in all patients. During the follow-up (range 1-4
      years), alkali replacement therapy corrected the systemic metabolic acidosis, and
      two patients demonstrated normal growth. rhGH therapy was administered to patient
      3 at the age of 6 years, and his growth rate was significantly improved (growth
      velocity 9.6 cm/yr). In total, 5 mutations were identified in our cohort of three
      patients, and four mutations were novel. CONCLUSIONS: We report the clinical and
      molecular characteristics of dRTA patients from China. The four novel mutations
      detected in our study extend the spectrum of gene mutations associated with
      primary dRTA. Furthermore, our study confirms the effect of early treatment in
      improving growth for dRTA patient and provides insight into the effects of rhGH
      on dRTA patients who were diagnosed late and exhibiting a persistent growth delay
      despite appropriate therapy.

PMID- 30230415
TI  - Examining interprofessional learning perceptions among students in a simulation
      based operating room team training experience.
AB  - High-fidelity simulation (HFS) operating room (OR) inter-professional team
      training improves healthcare students' team-based attitudes and behaviours. Such
      improvements can diminish tribalism among the professions in the OR by overcoming
      entrenched perceptions of team members. We investigated whether simulation-based
      interprofessional student OR team training impacts students differently based on
      their professional background. From 2010 to 2013, HFS OR interprofessional
      student team training sessions were conducted involving senior medical students,
      senior undergraduate nursing students, and nurse anaesthesia students. The
      training involved a two-scenario format, each followed by a structured debriefing
      focusing on team-based competencies. Before and after each session, students
      completed a 15-item teamwork competencies self-efficacy survey as well as, from
      2012-2013, the Readiness for Interprofessional Learning Scale (RIPLS). At the end
      of each session, they also completed a 6-item rating scale assessing overall team
      function during the session. Mean scores were calculated for each student
      professional group, post/pre mean differences were determined, and student t-test
      and ANOVA analyses were employed to compare within and between-group differences,
      respectively. Response rates were over 80% for each scale used. Medical students
      and undergraduate nursing students had significant improvements in team-based
      attitudes post- to pre-session. Medical students and nurse anaesthesia students
      had significant improvements in RIPLS scores. Statistically significant
      improvements from post- to pre-session were seen overall for both team-based
      attitudes (effect size = 0.83) and RIPLS (effect size = 0.37). The difference
      between the team-based scores between professions was significant; RIPLS
      differences were not. No significant difference existed between professions
      related to overall teamwork scores. HFS OR team training of healthcare students
      has beneficial but variable benefits for each professional group.

PMID- 30230416
TI  - Subcutaneous adipose tissue accumulation protects systemic glucose tolerance and
      muscle metabolism.
AB  - The protective effects of lower body subcutaneous adiposity are linked to the
      depot functioning as a "metabolic sink" receiving and sequestering excess lipid.
      This postulate, however, is based on indirect evidence. Mechanisms that mediate
      this protection are unknown. Here we directly examined this with progressive
      subcutaneous adipose tissue removal. Ad libitum chow fed mice underwent sham
      surgery, unilateral or bilateral removal of inguinal adipose tissue or bilateral
      removal of both inguinal and dorsal adipose tissue. Subsequently mice were
      separated into 5 week chow or 5 or 13 week HFD groups (N = 10 per group). Primary
      outcome measures included adipocyte distribution, muscle and liver triglycerides,
      glucose tolerance, circulating adipocytokines and muscle insulin sensitivity.
      Subcutaneous adipose tissue removal caused lipid accumulation in femoral muscle
      proximal to excision, however, lipid accumulation was not proportionally inverse
      to adipose tissue quantity excised. Accumulative adipose removal was associated
      with an incremental reduction in systemic glucose tolerance in 13 week HFD mice.
      Although insulin-stimulated pAkt/Akt did not progressively decrease among surgery
      groups following 13 weeks of HFD, there was a suppressed pAkt/Akt response in the
      non-insulin stimulated (saline-injected) 13 week HFD mice. Hence, increases in
      lower body subcutaneous adipose removal resulted in incremental decreases in the
      effectiveness of basal insulin sensitivity of femoral muscle. The current data
      supports that the subcutaneous depot protects systemic glucose homeostasis while
      also protecting proximal muscle from metabolic dysregulation and lipid
      accumulation. Removal of the "metabolic sink" likely leads to glucose intolerance
      because of decreased storage space for glucose and/or lipids.

PMID- 30230417
TI  - Shortcut to success? Negotiating genetic uniqueness in global biomedicine.
AB  - Since the sequencing of the human genome, as well as the completion of the first
      Human Genome Diversity Project, the benefits of studying one human population
      over another has been an ongoing debate relating to the replicability of findings
      in other populations. The leveraging of specific populations into research
      markets has made headlines in cases such as deCode in Iceland, Quebec Founder
      Population, and Generation Scotland. In such cases, researchers and policy makers
      have used the genetic and historical uniqueness of their populations to attract
      scientific, commercial and political interest. In this article, we explore how in
      countries with population isolates, such as Finland, the researchers balance
      considerations relating to the generalization and replicability of findings in
      small yet unique research populations to global biomedical research interests.
      This highlights challenges related to forms of competition associated with
      genetics research markets, as well as what counts as the 'right' population for
      genetic research.

PMID- 30230418
TI  - Brain-Resident T Cells Following Viral Infection.
AB  - Activated CD8+ lymphocytes infiltrate the brain in response to many viral
      infections; where some remain stationed long term as memory T cells. Brain
      resident memory T cells (bTRM) are positioned to impart immediate defense against
      recurrent or reactivated infection. The cytokine and chemokine milieu present
      within a tissue is critical for TRM generation and retention; and reciprocal
      interactions exist between brain-resident glia and bTRM. High concentrations of
      TGF-beta are found within brain and this cytokine has been shown to induce CD103
      (integrin alphaebeta7) expression. The majority of T cells persisting within
      brain express CD103, which aids in retention through interaction with E-cadherin.
      Likewise, cytokines produced by T cells also modulate microglia. The anti
      inflammatory cytokine IL-4 has been shown to preferentially polarize microglial
      cells toward an M2 phenotype, with a corresponding increase in E-cadherin
      expression. These findings demonstrate that the brain microenvironment, both
      during and following inflammation, prominently contributes to the role of CD103
      in T cell persistence. Further evidence shows that microglia, and astrocytes,
      upregulate programmed death (PD) ligand 1 during neuroinflammation, likely to
      limit neuropathology, and the PD-1: PD-L1 pathway also aids in bTRM generation
      and retention. Upon reactivation of quiescent neurotropic viruses, bTRM may
      respond to small amounts of de novo-produced viral antigen by rapidly releasing
      IFN-gamma, resulting in interferon-stimulated gene expression in surrounding
      glia, thereby amplifying activation of a small number of adaptive immune cells
      into an organ-wide innate antiviral response. While advantageous from an
      antiviral perspective; over time, recall response-driven, organ-wide innate
      immune activation likely has cumulative neurotoxic and neurocognitive
      consequences.

PMID- 30230420
TI  - How to train your oracle: The Delphi method and its turbulent youth in operations
      research and the policy sciences.
AB  - Delphi is a procedure that produces forecasts on technological and social
      developments. This article traces the history of Delphi's development to the
      early 1950s, where a group of logicians and mathematicians working at the RAND
      Corporation carried out experiments to assess the predictive capacities of groups
      of experts. While Delphi now has a rather stable methodological shape, this was
      not so in its early years. The vision that Delphi's creators had for their
      brainchild changed considerably. While they had initially seen it as a technique,
      a few years later they reconfigured it as a scientific method. After some more
      years, however, they conceived of Delphi as a tool. This turbulent youth of
      Delphi can be explained by parallel changes in the fields that were deemed
      relevant audiences for the technique, operations research and the policy
      sciences. While changing the shape of Delphi led to some success, it had severe,
      yet unrecognized methodological consequences. The core assumption of Delphi that
      the convergence of expert opinions observed over the iterative stages of the
      procedure can be interpreted as consensus, appears not to be justified for the
      third shape of Delphi as a tool that continues to be the most prominent one.

PMID- 30230421
TI  - Science writing in Greco-Roman antiquity.

PMID- 30230422
TI  - Is Payment for Egg Donation an Undue Inducement?
AB  - Should egg donors be paid? A negative answer might be offered on the ground that
      payment for egg donation is coercive. But is this viewpoint tenable? Is the offer
      of payment for egg donation really coercive? Even if not coercive, might payment
      for egg donation nonetheless be seen as exploitative? And if so why? The central
      argument of this paper focuses on the question whether the offer of payment for
      egg donation is an exploitative inducement and therefore an undue inducement.
      Another question raised in this paper is whether, given that it is commodifying,
      payment for egg donation constitutes a failure to recognize the giftedness and
      true value of human life.

PMID- 30230423
TI  - Working towards developing evidence based psychosocial interventions to promote
      health and wellbeing in pregnancy.

PMID- 30230424
TI  - The Neurostructure of Morality and the Hubris of Memory Manipulation.
AB  - Neurotechnologies that promise to dampen (via pharmacologicals), disassociate
      (via electro-convulsive therapy), erase (via deep brain stimulation), and replace
      (via false memory creation) unsavory episodic memories are no longer the subject
      of science fiction. They have already arrived, and their funding suggests that
      they will not disappear anytime soon. In light of their emergence, this essay
      examines the neurostructure of normative morality to clarify that memory
      manipulation, which promises to take away that which is bad in human experience,
      also removes that which enables human beings to be good. Concepts such as free
      will, moral responsibility, and the neurobiological basis of moral reasoning are
      explored to underscore the fundamental hubris inherent to the memory manipulation
      enterprise.

PMID- 30230425
TI  - Look before you leap: the role of negative urgency in appraisals of ambiguous and
      unambiguous scenarios in individuals high in generalized anxiety disorder
      symptoms.
AB  - Negative interpretation bias, the propensity to make threatening interpretations
      of ambiguous information, is associated with symptoms of generalized anxiety
      disorder (GAD). Apart from its relationship with intolerance of uncertainty (IU),
      little is known about what explains the presence of this cognitive bias in GAD.
      One factor may be negative urgency (NU), the tendency to take rash action when
      distressed, which is related to GAD symptoms and to cognitive biases in
      nonclinical populations. The aim of the present study was to examine the
      relationship between NU and interpretation bias in individuals high in GAD
      symptoms (N = 111). IU, trait anxiety, and other forms of impulsivity were
      examined concurrently as competing correlates of interpretation bias. Greater NU
      and IU were found to be unique correlates of greater threatening interpretations
      of ambiguous scenarios. Greater NU was also a unique correlate of greater
      threatening interpretations of negative and positive scenarios. No other forms of
      impulsivity were uniquely related to interpretation bias. The findings suggest
      that greater NU may have a role in the tendency for individuals high in GAD
      symptoms to make threatening interpretations in response to ambiguous scenarios,
      overtly threatening situations, and situations without indication of threat or
      danger. Theoretical implications of these findings are discussed.

PMID- 30230426
TI  - Utilisation of waste medicine wrappers as an efficient low-cost electrode
      material for microbial fuel cell.
AB  - Waste generation from healthcare facilities now has become a concerning issue as
      it contain plastic and metals. Medicine wrappers are one of the major portions of
      healthcare solid waste, which impel intensive solid waste management practice due
      to fewer possibilities of deriving by-products. However, it can be recycled and
      used as an electrode material in microbial fuel cells (MFCs). An electrode
      material for application in MFCs is a crucial component, which governs total
      fabrication cost as well as power recovery, thus a cost-effective, stable and
      durable electrode is essential. In this endeavour, a new metallic (aluminium)
      waste material, a waste medicine wrapper (WMW), was evaluated for feasibility to
      be used as anode/cathode in MFCs. Based on the stability test under corrosive
      environment (1 N KCl), the WMW electrode sustained a maximum current of 46 mA
      during cyclic voltammetry (CV) and noted only 14% reduction in current at an
      applied voltage of +0.4 V after 2500 s in chronoamperometry, indicating its good
      stability. Power recovery from MFC using WMW was higher than the MFC using bare
      carbon felt as an anode (27 vs. 21 mW/m2). The entire analytical test results
      viz. CV, electrochemical impedance spectroscopy and power performance established
      WMW as an excellent anode rather than cathode material.

PMID- 30230427
TI  - Tin and silver recovery from wave soldering dross.
AB  - This work proposes a method for the recovery of tin and silver from wave
      soldering dross produced during the manufacture of printed circuit boards.
      Samples of wave soldering dross were first subjected to carbothermic reduction to
      obtain an ingot containing the above metals plus other elements. This ingot was
      then subjected to electrorefining at different densities of electrical current,
      electrolyte flow rate, and cathode-anode separation distance, to determine the
      optimum conditions for recovering pure tin. Under such conditions, 82 wt% of the
      tin in the ingot was recovered at a purity of 99.94%. After subjecting ingots to
      continuous electrorefining under optimum conditions for 845 h, the slime
      collected at the anode was removed for the recovery of silver. This slime was
      subjected to thin-layer leaching with concentrated nitric acid. The leachate
      produced was subjected to copper-cementation; the silver adhering to the copper
      rod was collected by washing. This process recovered 92% of the silver in the
      wave soldering dross ingot at a purity of >99.6%. Some 99% of the copper entering
      the leachate from the copper rod during cementation was recovered by liquid
      liquid extraction with 40% LIX84 (dissolved in EXXOL D100). This method could
      provide a rapid, inexpensive means of recovering pure tin and silver from wave
      soldering dross.

PMID- 30230428
TI  - Comparing cognitive fusion and cognitive reappraisal as predictors of college
      student mental health.
AB  - Transdiagnostic cognitive behavioral interventions target different cognitive
      processes to promote mental health, including cognitive fusion and cognitive
      reappraisal. Determining the relative impact of cognitive fusion and reappraisal
      on a range of student mental health concerns could help interventions target
      psychopathological cognitive processes more effectively. Therefore, this study
      examined the longitudinal impact of cognitive fusion and reappraisal on mental
      health and functioning outcomes. A series of hierarchical regression models
      tested the effects of cognitive fusion and reappraisal in a sample of college
      students (n = 339). When controlling for reappraisal and baseline symptoms,
      fusion predicted distress, depression, generalized anxiety, social anxiety,
      hostility, academic distress, and student role problems 1 month later.
      Reappraisal predicted only student role problems longitudinally when controlling
      for fusion. These results suggest that cognitive fusion is a stronger predictor
      than reappraisal for a range of student mental health concerns and may be a
      particularly important target for improving student mental health.

PMID- 30230429
TI  - Evaluating The Swedish Approach to Motivating Improved Work Safety Conditions on
      Farms: Insights from Fear Appeals and the Extended Parallel Processing Model.
AB  - Farm work safety intervention programs based on educating and informing have been
      criticized for not demonstrably improving work safety. We argue that these
      criticisms are misplaced and that the problem with educating and informing lies
      not necessarily in the tool, but rather in its implementation. We arrive at this
      conclusion by systematically investigating eight of the largest farm work safety
      interventions in Sweden. In particular, we describe how they use fear and other
      emotional appeals in their communications in an attempt to motivate improved work
      safety. We then analyze their implementation using the extended parallel
      processing model (EPPM). We show that, although threat of injury and death is
      used in the majority of these interventions to motivate individuals, the threat
      is inconsistent with the behaviors targeted. Other shortcomings and implications
      for implementing wide-scale farm work safety interventions are discussed.

PMID- 30230430
TI  - A Review of 2016-2017 Agricultural Youth Injuries Involving Skid Steers and a
      Call for Intervention and Translational Research.
AB  - Skid steers or loaders are becoming prolific in U.S. agriculture - as are the
      injuries and fatalities related to their use. A review of incidents as queried in
      AgInjuryNews from 2016 to 2017 revealed an overrepresentation of youth being
      involved in these tragic incidents. This raises concerns over parental attitudes
      and beliefs about the safety of these machines. Skid steer incidents do not
      appear to be a result from a lack of safety education materials, however. Indeed,
      manufacturers, the Centers for Disease Control, and many state extension systems
      have safety manuals and general instruction, including YouTube videos and online
      resources. Thus, there appears to be a significant gap between safety knowledge
      and practice. There is also a lack of published research, including intervention
      strategies, training evaluation, and translational/implementation studies
      specific to skid steer machines. This review of youth incidents is therefore also
      a call for further research for foundational studies regarding attitudes and
      behaviors involving skid steers in agriculture, intervention models, and efforts
      to translate prevention knowledge beyond the existing materials.

PMID- 30230431
TI  - Occupational Injuries of Aquaculture Workers: Washington State.
AB  - OBJECTIVE: To characterize occupational injuries of aquaculture workers in
      Washington State. METHODS: We reviewed accepted Washington State workers'
      compensation claims from January 1, 2006 to December 31, 2014. Trends in
      employment, worker demographics (including age, sex, and body mass index), claim
      rate, and injury characteristics were summarized for accepted claims in the
      Washington State risk classes that include aquaculture workers. RESULTS: During
      the nine-year study period, there were 1,180 accepted claims, 836 (65.1%) were
      medical-aid only and 344 (26.8%) were compensable. Most commonly reported injury
      types included being struck by/against an object (n = 420) and work-related
      musculoskeletal disorders (n = 310). Over the study period, there was no
      statistically significant change in claim rates in aquaculture (p = 0.77), though
      they were elevated compared to claim rates for all WA industries combined. A
      significant upward trend (p = 0.003) in aquaculture employment was observed
      during our study period. CONCLUSIONS: Given the growth in aquaculture production,
      and that aquaculture workers in Washington are experiencing higher occupational
      injury rates compared to other workers in the state, our study suggests that the
      industry should devote greater attention to prevention of work-related injuries,
      especially those resulting in being struck by/against objects or work-related
      musculoskeletal disorders. Enhanced occupational safety and health programs for
      this industry could help reduce injuries, as well as the cost of workers'
      compensation claims.

PMID- 30230432
TI  - Migrant Farmworker Nutritional Strategies: Implications for Diabetes Management.
AB  - OBJECTIVES: Diabetes is a chronic disease prevalent in Hispanic/Latino adults,
      including migrant farmworkers in the US. Its management requires that individuals
      follow dietary guidelines, which may be difficult for migrant farmworkers due to
      work and environmental constraints. This analysis is designed to explore
      potential barriers to and supports for migrant farmworkers' practice of effective
      dietary self-management. METHODS: Interviews were conducted with 200 Latino
      migrant farmworkers in North Carolina, including workers with and without
      diabetes, recruited at housing sites throughout the 2017 agricultural season. The
      survey instrument included questions designed to elucidate how workers obtain
      food, prepare and consume food, and maintain food security. RESULTS: Most
      purchased food is obtained once per week at large grocery stores, with most
      farmworkers depending on others for transportation. Less than 1 in 5 supplement
      with garden produce and food from food pantries, farmers markets, and hunting and
      fishing. About half of lunches and a quarter of dinners are purchased from
      vendors or other commercial sources. More than 2 in 5 workers report they have to
      compromise on or lack control of meal content. About 1 in 5 report issues with
      food security. CONCLUSIONS: The food-related practices of farmworkers would
      require change to accommodate effective dietary self-management of diabetes.
      Greater use of sources of fresh produce and other nutrient-dense foods, coupled
      with greater control over meal content and cooking techniques would be needed.
      While some accommodations could be encouraged through education, others would
      require policy change in housing or access to community resources.

PMID- 30230433
TI  - Technology Use Among Youth While Operating Farm Equipment.
AB  - Distracted driving by using modern technologies has been linked with increased
      risk of injuries, however, the current research has focused primarily on the use
      of technology while operating roadway vehicles. The purpose of this study was to
      explore the use of technology while operating farm equipment among members of an
      agricultural youth organization (Pennsylvania FFA Association members). An online
      survey was used to examine the use of technology while operating a tractor,
      ATV/UTV, skid steer, and truck/car. Survey responses with 10 types of technology
      use were analyzed in relation to a wide variety of factors including frequency of
      use, safety beliefs, safety concern, and seeing others using technology. One
      hundred forty-three youth completed the questionnaire in 2017. Eighty-eight
      percent of youth surveyed used technology to some extent while operating farm
      equipment. Self-reported technology use was most influenced by safety beliefs and
      seeing others using technology while operating farm equipment regardless of the
      farm equipment type. Findings from this study provide insights into factors
      behind technology use while engaged in farm work-related driving by youth.

PMID- 30230437
TI  - Certified Safe Farm Implementation in North Carolina: Hazards, Safety
      Improvements, and Economic Incentives.
AB  - OBJECTIVES: Certified Safe Farm (CSF) is a multimodal intervention composed of
      four components: safety, health, education, and economic incentive. North
      Carolina has conducted the largest implementation of CSF outside of the
      Midwestern United States where it was developed. This paper describes the
      Efficacy dimension of the Reach Effectiveness Adoption Implementation Maintenance
      (RE-AIM) framework for the implementation of CSF in North Carolina during 2009
      2012 on 113 farms in a three-county, highly productive and diverse agricultural
      area. METHODS: Using descriptive statistics, analysis of variance, correlational
      analyses, and logistic regression, quantitative data were examined from on-farm
      safety reviews, as well as primary operators' use of cost-share funds as an
      economic incentive (34% participation) to make identified safety and health
      improvements on the farm. RESULTS: Overall farm safety review scores were
      generally high (96% passing rate). Category scores revealed hazards in seven key
      categories: Chemical Storage; Tractors; Machine Shop, Repair Area; Gravity Flow,
      Auger, and Forage Wagons; Portable Augers; Dairy and Beef Structures; and Swine
      and Poultry Structures. The cost-share economic incentive component was utilized
      in addressing hazards in five of these categories, as well as in nine others. The
      average per farm cost-share reimbursement was $3,276, with a median of $1,615. In
      total, an investment of $255,307 (farmer investment plus incentive) was made in
      safety and health improvements on farms (n = 38). Correlation and logistic
      regression analyses revealed no significant relationships among scores, cost
      share investments, and selected farm demographics. CONCLUSION: Findings suggest
      the 50% cost-share for safety and health improvements is a promising economic
      incentive model for CSF implementation.

PMID- 30230435
TI  - Pesticide use, allergic rhinitis, and asthma among US farm operators.
AB  - OBJECTIVE: The objective of the study is to examine associations between use of
      specific pesticides and lifetime allergic rhinitis and current asthma in US
      primary farm operators. METHODS: The 2011 Farm and Ranch Safety Survey data from
      11,210 primary farm operators were analyzed. Pesticide use on the farm was
      determined using an affirmative response to the question of whether the operator
      ever mixed, loaded, or applied pesticides on their farm in the 12 months prior to
      the interview. Operators who answered "yes" were further asked about the specific
      trade name and formulation identifiers of the product they used and personal
      protective equipment (PPE) used. Data were weighted to produce national
      estimates. Adjusted prevalence odds ratios (PORs) were calculated using logistic
      regression. The referent group included operators who did not use any pesticides
      in the 12 months prior to the interview. RESULTS: Of an estimated 2.1 million
      farm operators, 40.0% used pesticides, 30.8% had lifetime allergic rhinitis, and
      5.1% had current asthma. Insecticide and herbicide use were significantly
      associated with lifetime allergic rhinitis and current asthma. The use of 2,4
      dichlorophenoxyacetic acid (POR = 1.5; 95% CI 1.2-1.9) and carbaryl (POR = 2.3;
      1.4-3.7) was significantly associated with lifetime allergic rhinitis. Of
      operators using pesticides, 64.9% used PPE the last time they mixed, loaded, or
      applied pesticides. CONCLUSIONS: Pesticide use was associated with lifetime
      allergic rhinitis and current asthma among farm operators. Further studies are
      needed to clarify the dose-response relationship between pesticide use and
      adverse respiratory health effects.

PMID- 30230436
TI  - Using mobile technology to increase safety awareness among dairy workers in the
      United States.
AB  - BACKGROUND: Modern U.S. dairy farm operations present multiple safety hazards
      which may result in worker injuries, illnesses and fatalities. The U.S. industry
      trend towards large-herd milking operations, especially in the Western U.S.,
      necessitates an increased number of workers on each farm. The U.S. dairy
      workforce is comprised of an increasing percentage of immigrant workers with
      limited English proficiency which presents a safety training challenge. Our
      objective was to develop, deliver and evaluate safety awareness training to U.S.
      dairy farm workers using mobile tablets as a personal learning environment.
      METHODS: A non-random sample of 1,436 dairy workers received safety awareness
      training on a mobile device platform. Kirkpatrick Levels 1, 2 and 3 training
      effectiveness evaluations were performed. RESULTS: Approximately 58.7% of
      training participants received a middle school education, and 22.7% were from
      Guatemala who reported K'iche' as their native language. A statistically
      significant large effect size suggests safety knowledge was gained among training
      participants when comparing post-test scores to pre-test scores (Level-2).
      Training participants rated their training experience favorably (Level-1), and
      applied knowledge gained in their daily work activities three months after
      training (Level-3). CONCLUSION: Our findings suggest the utilization of mobile
      learning techniques is an effective means to deliver safety awareness training
      content to dairy workers. Dairy worker safety training should be culturally,
      linguistically, and literacy appropriate and comprehensive in nature to include
      all applicable dairy safety hazards. Our observations support the use of mobile
      devices as just one component of a more comprehensive health and safety
      management program on farms.

PMID- 30230438
TI  - Tooth wear during orthodontic treatment with fixed appliances: a systematic
      review.
AB  - OBJECTIVES: Tooth wear, additional to the physiologic alterations of the
      dentition, may occur during orthodontic treatment. The objective of the present
      review was to investigate systematically the literature relevant to its
      progression in patients having undergone comprehensive orthodontic treatment.
      DATA SOURCES: Search without restrictions in eight databases since inception and
      hand searching until October 2017 was performed. DATA SELECTION: Studies
      evaluating tooth wear immediately before and after the completion of orthodontic
      treatment with fixed appliance were evaluated independently and in duplicate.
      DATA EXTRACTION: Following study retrieval and selection, data on volumetric and
      surface tooth wear was extracted. Individual study risk of bias assessment was
      performed using the Risk Of Bias In Non-randomised Studies - of Interventions
      (ROBINS-I) tool, and the overall quality of the evidence was assessed with the
      Grades of Recommendation, Assessment, Development and Evaluation approach. DATA
      SYNTHESIS: All three finally included studies reported wear of teeth during the
      period of treatment but were at serious risk of bias. Two of them investigated
      tooth wear by 3D volumetric measurements and one used grading scales. The mean
      volume reduction was 1.02 mm3 per tooth for the incisor group [95% Confidence
      Interval (CI): 0.84-1.20], 1.62 mm3 for the canines [95% CI: 0.8-2.38; I2 = 96%;
      random effects method] and 0.95 mm3 for premolars and molars [95% CI: 0.84-1.07].
      The overall quality of evidence limited the confidence in the observed estimates.
      CONCLUSIONS: Varying degrees of tooth wear were reported after comprehensive
      orthodontic treatment. Further studies are needed in order to elucidate how much
      is associated with orthodontic treatment and/or physiologic alterations of the
      dentition.

PMID- 30230440
TI  - All I want for Christmas ... is an undergraduate GP curriculum.

PMID- 30230441
TI  - Marinifilum breve sp. nov., a marine bacterium isolated from the Yongle Blue Hole
      in the South China Sea and emended description of the genus Marinifilum.
AB  - A Gram-stain-negative, facultative anaerobic, non-motile, short-clavate and non
      flagellated marine bacterium strain, designated JC075T, was isolated from the
      Yongle Blue Hole in the South China Sea. Based on the 16S rRNA gene sequence,
      strain JC075T was found to be closely related to Marinifilum albidiflavum FB208T
      (97.10 %), Marinifilum flexuosum DSM 21950T (96.43 %) and Marinifilum fragile JCM
      15579T (95.58 %), with less than 90.24 % sequence similarity to other genera of
      the family Marinifilaceae. The growth temperature was in the range of 10-37 
      degrees C, and the optimum temperature was 16  degrees C. Optimal growth occurred
      at pH 7.0 and in the presence of 3 % (w/v) NaCl. The isoprenoid quinone of strain
      JC075T was identified as menaquinone-7 and the predominant fatty acids (>10 %)
      were iso-C15 : 0 (47.9 %), summed feature 9 (C17 : 1 or/and iso-C17 : 1omega9c;
      18.7 %) and iso-C17 : 0 3-OH (14.9 %). The major polar lipids were one
      phosphatidylethanolamine, one phospholipid, one aminophospholipid, one
      glycolipid, one aminolipid and two unidentified lipids. The DNA G+C content of
      strain JC075T was 35.8 mol%. On the basis of polyphasic analysis, strain JC075T
      was considered to represent a novel species of the genus Marinifilum, for which
      the name Marinifilumbreve sp. nov. is proposed. The type strain is JC075T (=KCTC
      15646T=MCCC 1K03477T=JCM 32401T).

PMID- 30230443
TI  - Generation of a potential koi herpesvirus live vaccine by simultaneous deletion
      of the viral thymidine kinase and dUTPase genes.
AB  - Koi herpesvirus (KHV, Cyprinidherpesvirus 3) causes a fatal disease of koi and
      common carp. To obtain safe and efficacious live vaccines, we generated deletion
      mutants of KHV lacking the nonessential genes encoding two enzymes of nucleotide
      metabolism, thymidine kinase (TK, ORF55) and deoxyuridine-triphosphatase (DUT,
      ORF123). Since single-deletion mutants based on a KHV isolate from Israel (KHV-I)
      only exhibited partial attenuation (Fuchs W, Fichtner D, Bergmann SM,
      Mettenleiter TC. Arch Virol 2011;156 : 1059-1063), a corresponding double mutant
      was generated and tested in vivo, and shown to be almost avirulent but still
      protective. To overcome the low in vitro virus titres of KHV-I (<=105 p.f.u. ml
      1), single and double TK and DUT deletions were also introduced into a cell
      culture-adapted KHV strain from Taiwan (KHV-T). The deletions did not affect in
      vitro virus replication, and all KHV-T mutants exhibited wild-type-like plaque
      sizes and titres exceeding 107 p.f.u. ml-1, as a prerequisite for economic
      vaccine production. Compared to wild-type and revertant viruses, the single
      deletion mutants of KHV-T were significantly attenuated in vivo, and immersion of
      juvenile carp in water containing high doses of the double mutant caused almost
      no fatalities. Nevertheless, the deletion mutants induced similar levels of KHV
      specific serum antibodies to the parental wild-type virus, and conferred solid
      protection against disease after challenge with wild-type KHV. For the convenient
      differentiation of DNA samples prepared from gill swabs of carp infected with
      wild-type and TK-deleted KHV we developed a triplex real-time PCR. Thus, KHV
      TDeltaDUT/TK might be suitable as a genetic DIVA vaccine in the field.

PMID- 30230442
TI  - Brachybacterium endophyticum sp. nov., a novel endophytic actinobacterium
      isolated from bark of Scutellaria baicalensis Georgi.
AB  - A Gram-positive, aerobic, coccus-shaped, non-spore-forming actinobacterium,
      designated strain M1HQ-2T, was isolated from a surface-sterilized bark of
      Scutellaria baicalensis Georgi collected from Guizhou, China and tested using a
      polyphasic approach to determine its taxonomic position. Strain M1HQ-2T grew at 4
      37  degrees C (optimum, 30  degrees C), pH 5.0-11.0 (pH 8.0) and in the presence
      of 0-15 % (w/v) NaCl (1-3 %). Substrate mycelia and aerial mycelia were not
      formed, and diffusible pigments were not observed on any media tested.
      Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain M1HQ
      2T belonged to the genus Brachybacterium and had the highest 16S rRNA gene
      sequence similarity of 97.6 % to Brachybacteriumsquillarum M-6-3T. Strain M1HQ-2T
      contained MK-7 as the dominant menaquinone. The cell-wall peptidoglycan contained
      meso-diaminopimelic acid. The polar lipids profile of strain M1HQ-2T contained
      diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an
      unidentified lipid. The predominant fatty acids were anteiso-C15 : 0 and anteiso
      C17 : 0. The DNA G+C content of strain M1HQ-2T was 71.0 mol%. The average
      nucleotide identity value between strain M1HQ-2T and type strain of
      Brachybacterium sacelli was 76.7 %. The estimated DNA-DNA hybridization value
      between strain M1HQ-2T and type strain of B. sacelli was 20.6 %. On the basis of
      phylogenetic analysis, chemotaxonomic characteristics and phenotypic data, strain
      M1HQ-2T represents a novel species of the genus Brachybacterium, for which the
      name Brachybacteriumendophyticum sp. nov. is proposed. The type strain is M1HQ-2T
      (=KCTC 49087T=CGMCC 1.16391T).

PMID- 30230444
TI  - Comparison of three commercial multiplex PCR assays for the diagnosis of
      intestinal protozoa.
AB  - Although microscopic examination of stool samples remains the reference method
      for the diagnosis of intestinal protozoal infections, these techniques are time
      consuming and require operators who are experienced and well trained. Molecular
      biology seems to offer performances at least equivalent in terms of sensitivity
      and specificity for certain parasites. This study aimed to compare three
      multiplex PCR assays on 93 prospectively collected positive stools (prospective
      cohort) and a panel of 12 more Cryptosporidium-positive samples (Cryptosporidium
      panel). On the prospective cohort, the sensitivity was 89%, 64% and 41% for
      Giardia sp. detection for BD MaxTM, G-DiaParaTM and RIDA(r)GENE, respectively and
      75%, 100% and 100% for C. parvum/hominis detection. The sensitivity of the
      RIDA(r)GENE assay for all Cryptosporidium species was 100%, and for D. fragilis
      71%. All the techniques obtained the same results for E. histolytica detection,
      with one positive sample. All species in the Cryptosporidium panel were
      identified by the RIDA(r)GENE PCR. The BD MaxTM and G-DiaParaTM assays detected
      only C. parvum/hominis with the exception of one positive sample for C.
      meleagridis. No assay showed satisfactory results for all parasites
      simultaneously, and the DNA extraction seems to be the critical step. More
      studies are needed to standardize this procedure.

PMID- 30230446
TI  - [From HGP-write to " Ultra-safe Cells "].
AB  - The HGP-write project, announced in 2016 but not really implemented yet, comes
      back as a project aimed at constructing an "ultra-safe" human cell line fully
      resistant to virus infection and with other desirable characteristics. This
      involves introducing 400,000 changes in the genome and raises a number of
      technical and financial issues, but may become realistic in mid-term.

PMID- 30230447
TI  - [Genetic data sharing: a new type of capital].
AB  - Over the last three decades, various biotech companies, mostly in North America,
      have become experts in the production, processing and analysis of large volumes
      of genetic data. They have surpassed the performance of traditional academic
      platforms, by appropriating a new economic model: the two-sided market. Thus, by
      applying web 2.0 ideas, these biotech companies have made it possible for
      millions of users to produce and "share" data including genetic data, with each
      other and with third parties through a digital network rich in information and
      "free" services. However, in reality, data have become a means of payment for
      access to these networks and the use of these services. In the era of the digital
      economy, data sharing has become synonymous with commercial exchange and genetic
      data synonymous with capital.

PMID- 30230445
TI  - Taenia solium cysticercosis in West Africa: status update.
AB  - Cysticercosis is caused by the larvae of the cestode Taenia solium. Few data are
      available on the prevalence of this disease in pigs and humans in West African
      countries. The aim of this study was to provide an overview of existing data
      concerning the spread of this parasitosis in the countries of the Economic
      Community of West African States (ECOWAS) on the basis of the literature
      published over the last five decades. Systematic searches for publications were
      carried out on PubMed and Google Scholar, as well as in certain regional and
      local journals. From a total of 501 articles initially retrieved concerning T.
      solium cysticercosis in West African countries, only 120 articles were relevant
      for this review and therefore finally retained. For pigs, only eight out of
      sixteen countries of the region have reported porcine cysticercosis. Post-mortem
      examination of carcasses at slaughterhouses, meat inspection at butcheries or
      tongue inspection in herds have been the main source of data, but may not
      entirely reflect actual parasite distribution. For humans, only five out of
      sixteen countries reported epidemiological data on neurocysticercosis. Most data
      referred to neurocysticercosis prevalence among epileptic patients or isolated
      clinical cases. Furthermore, existing data are often old. Overall, T. solium
      cysticercosis remains largely neglected in West Africa, and its prevalence
      appears not to be affected by any religion in particular. There is an urgent need
      to promote and implement health partnerships and programs on this disease in
      order to collect more data and identify sensitive populations in the countries of
      the ECOWAS area.

PMID- 30230448
TI  - [Social environment, biological embedding and social inequalities in health].
AB  - The social gradient in health refers to the fact that the higher individuals rise
      in the social hierarchy, the better is their health. Understanding the
      construction of this gradient is a major challenge in social epidemiology. An
      original approach consists in looking at how the different exposures (chemical,
      physical, behavioural, psychosocial...) associated with the social environment
      are ultimately expressed at the biological level influencing health positively or
      negatively, referring to the concept of biological embedding. Data from animal
      models and life course epidemiology have shed new light on the biological
      mechanisms potentially at play. Recent discoveries from the field of epigenetics
      provide a better understanding of how the social environment, especially the
      early environment, can influence biological functioning over the long term or
      even over several generations. The work on the biological embedding of the social
      environment in connection with epigenetics still needs to be very largely
      consolidated, but could constitute a change of perspective in human biology,
      particularly by reconsidering the influence of the environment on biological
      functioning, which is not without consequences in terms of public health
      interventions.

PMID- 30230449
TI  - [The digital pill, between beneficence and vigilance: ethical stakes].
AB  - Since November 2017, the digital pill, which makes it possible to know whether a
      patient has achieved compliance or not with the treatment has become a reality.
      This drug can benefit the patients by helping them to better follow their
      treatment and avoid misuse. However, even though the use of this device requests
      patient consent, major questions arise regarding the respect for privacy and
      freedom of action. Evidently, the correct use of drugs is both a public health
      and economic issue, but through this digital tool, the temptation could be to
      implement measures to control citizens, in particular regarding the use of
      treatments that affect health expenditure. A too prescriptive conception of
      monitoring algorithms could alter the care relationship, denying the part of
      adaptation that a patient can legitimately claim in taking his treatment. The
      digital pill could be a helpful tool but it is necessary to evaluate its fair
      place in terms of respect for the person and adequacy with its liberties.

PMID- 30230450
TI  - [P-TEFb and Brd4: actors of the transcription pause release as therapeutical
      targets].
AB  - Most cell physiology events are dictated by the integration of perceived signals
      and the elaboration by cells of adapted answers via the execution of proper
      transcriptional programs. In order to ensure an optimal control of these answers,
      many regulation mechanisms have been selected throughout the evolution, thus
      allowing to fine-tune transcript expression. The transcriptional pause and its
      release by P-TEFb (Positive Transcription Elongation Factor) have been evidenced
      two decades ago. Since then, the importance of such mechanisms has been
      highlighted by the association between alterations of this machinery and the
      appearance of diseases. P-TEFb and Brd4 have thus recently emerged as potential
      therapeutical targets for cancers and AIDS notably. In this review, we present a
      brief case history and an up-to-date synthesis of models for transcriptional
      pause release. We later discuss on the pathophysiological processes associated
      with this mechanism and clinical trials targeting Brd4 and P-TEFb.

PMID- 30230451
TI  - [Restoration of damaged cortical pathways by neural grafting].
AB  - The motor cortex plays a central role in the control, planning, and execution of
      voluntary motor commands in mammals. The loss of cortical neurons is a common
      feature of many neuropathological conditions such as traumatic and ischemic
      lesions or several neurodegenerative diseases. Cell transplantation presents a
      promising therapeutic strategy to overcome the limited abilities of axonal
      regrowth and spontaneous regeneration of the adult central nervous system. In
      this review, we will present a historical review of brain transplantation and the
      current state of research in the field of cortical transplantation.

PMID- 30230452
TI  - [Innate immunity evasion mechanisms of filoviruses].
AB  - Ebola virus is an important pathogen that emerged in Central Africa where it was
      responsible of numerous outbreaks of haemorrhagic fevers associated with a
      extremely high mortality rate (up to 90%). The filovirus pathogenicity is related
      to an inappropriate antiviral response. Indeed, this family of viruses has
      developed evasion strategies from early innate immunity mechanisms. As a result,
      a massive viral replication induces an unsuitable immune response causing an
      acute inflammatory reaction associated with the haemorrhagic syndrome. In this
      review, we describe the mechanisms adopted by filoviruses like Ebola virus to
      escape innate immunity response.

PMID- 30230453
TI  - [Bipartite organization of human lymphopoiesis].
AB  - Due to difficulties to access primary bone marrow samples, human hematopoiesis
      has long remained far less characterized than in the mouse. Using an in vivo
      modeling approach of fetal hematopoiesis in humanized mice, we recently showed
      that human lymphoid cells stem from two functionally specialized populations of
      CD127- and CD127+ early lymphoid progenitors (ELP) that differentiate
      independently, respond differently to growth factors, undergo divergent modes of
      lineage restriction and generate distinct lymphoid populations. Our results
      demonstrate that, conversely to the mouse, human lymphopoiesis displays a
      bipartite developmental architecture.

PMID- 30230454
TI  - [The multiple functions of the hepatitis B virus core protein: new research
      directions and therapeutic challenges].
AB  - Chronic infection by hepatitis B virus (HBV) is a major public health problem
      with more than 250 millions of people chronically infected worldwide who have a
      high risk to develop cirrhosis and hepatocellular carcinoma. Available treatments
      reduce viremia but do not eradicate the virus from hepatocytes. Therefore, there
      is an urgent need to develop new classes of antiviral molecules and the viral
      capsid protein, Core, constitutes a new favored target. Core protein Allosteric
      Modulators (CAMs) targeting its assembly functions are in clinical development.
      In addition, investigation of Core regulatory functions may lead to the
      development of compounds targeting cellular factors (HTA) that could be used in
      combined therapies aiming to achieve a better control of HBV replication.

PMID- 30230455
TI  - [MacP, a regulator of the cell wall assembly in the human bacterial pathogen
      Streptococcus pneumoniae].

PMID- 30230456
TI  - [Non-antibiotic drugs have large effect on the intestinal microbiota].

PMID- 30230457
TI  - [In bacteria veritas: pronostic role of intestinal microbiote in cancer therapy].

PMID- 30230459
TI  - [The pericyte of the pancreatic islet regulates capillary diameter and local
      blood flow].

PMID- 30230458
TI  - [Video games and mental health].

PMID- 30230460
TI  - [The TOR SAGA to the rescue of starved yeast cells].

PMID- 30230461
TI  - [The delta family of glutamate receptors].

PMID- 30230462
TI  - [New light shed on thalamocortical excitability in absence epilepsy].

PMID- 30230463
TI  - [Reptin: a new therapeutic target for metabolic syndrome and fatty liver
      diseases].

PMID- 30230464
TI  - [Adherence and new technologies: a new look at an old problem].
AB  - In medicine, new information and communication techniques find their interest in
      the effectiveness and safety of treatments, without ignoring the fact that not
      all patients will be able to benefit from these techniques without mastering
      them.

PMID- 30230465
TI  - [Suicide prevention and eHealth: towards personalized follow-up strategies?]
AB  - Suicide risk assessment usually rely on brief medical visit and does not report
      the evolution of this risk after the patient discharge. However, the reattempt
      risk is still high several months after the initial attempt. In these setting,
      long term suicide prevention of at risk subjects are challenging. Thanks to
      recent technological advances, electronic health (eHealth) data collection
      strategies now can provide access to real-time patient self-report data during
      the interval between visits. The extension of the clinical assessment to the
      patient environment and data processing using data mining will support medical
      decision making.

PMID- 30230466
TI  - [Even the Warburg effect can be oxidized: metabolic cooperation and tumor
      development].
AB  - During tumor development, malignant cells rewire their metabolism to meet the
      biosynthetic needs required to increase their biomass and to overcome their
      microenvironment constraints. The sustained activation of aerobic glycolysis,
      also called Warburg effect, is one of these adaptative mechanisms. The progresses
      in this area of research have revealed the flexibility of cancer cells that
      alternate between glycolytic and oxidative metabolism to cope with their
      conditions of development while sharing their energetic resources. In this
      survey, we review these recent breakthroughs and discuss a model that likens
      tumor to an evolutive metabolic ecosystem. We further emphasize the ensuing
      therapeutic applications that target metabolic weaknesses of neoplastic cells.

PMID- 30230468
TI  - [IDO, an enzyme that induces dangerously obesity].

PMID- 30230467
TI  - [Usutu virus: the phantom menace].
AB  - Usutu virus, an arbovirus discovered in Africa in 1959, has spread over a large
      part of Europe over the last twenty years causing significant bird mortality as
      reported in France since 2015. The zoonotic risk, associated with this succession
      of avian epizootics in Europe, deserves to be taken into account even if human
      cases remain rare to date. Human infections are most often asymptomatic or
      present a benign clinical expression. However, neurological complications such as
      encephalitis or meningoencephalitis have been described. In addition, the recent
      description of an atypical case of facial paralysis in France suggests that the
      clinical spectrum of infections caused by Usutu virus is not fully characterized.
      Finally, the recent history of other arboviral outbreaks invites the scientific
      community to be extremely vigilant.

PMID- 30230469
TI  - [France, a refuge for researchers in danger].

PMID- 30230470
TI  - [A biological anthropology of the disappearance of the Neandertal Man: recent
      data].
AB  - What could have been the causes of the disappearance of Neanderthals? We will try
      here to make a synthesis between one of the fundamental questions of biological
      anthropology relating to human evolution (hypotheses on the causes of the
      extinction of Neanderthals) and evolutionary bio-medical concepts, some of which
      have recently been reformulated thanks to the progress of paleogenomics
      (ancestral inheritance of the current human immune system, paleo-microbiology,
      host-pathogen relationship...).

PMID- 30230472
TI  - Humidity response depends on the small soluble protein Obp59a in Drosophila.
AB  - Hygrosensation is an essential sensory modality that is used to find sources of
      moisture. Hygroreception allows animals to avoid desiccation, an existential
      threat that is increasing with climate change. Humidity response, however,
      remains poorly understood. Here we find that humidity-detecting sensilla in the
      Drosophila antenna express and rely on a small protein, Obp59a. Mutants lacking
      this protein are defective in three hygrosensory behaviors, one operating over
      seconds, one over minutes, and one over hours. Remarkably, loss of Obp59a and
      humidity response leads to an increase in desiccation resistance. Obp59a is an
      exceptionally well-conserved, highly localized, and abundantly expressed member
      of a large family of secreted proteins. Antennal Obps have long been believed to
      transport hydrophobic odorants, and a role in hygroreception was unexpected. The
      results enhance our understanding of hygroreception, Obp function, and
      desiccation resistance, a process that is critical to insect survival.

PMID- 30230471
TI  - Insulin regulates POMC neuronal plasticity to control glucose metabolism.
AB  - Hypothalamic neurons respond to nutritional cues by altering gene expression and
      neuronal excitability. The mechanisms that control such adaptive processes remain
      unclear. Here we define populations of POMC neurons in mice that are activated or
      inhibited by insulin and thereby repress or inhibit hepatic glucose production
      (HGP). The proportion of POMC neurons activated by insulin was dependent on the
      regulation of insulin receptor signaling by the phosphatase TCPTP, which is
      increased by fasting, degraded after feeding and elevated in diet-induced
      obesity. TCPTP-deficiency enhanced insulin signaling and the proportion of POMC
      neurons activated by insulin to repress HGP. Elevated TCPTP in POMC neurons in
      obesity and/or after fasting repressed insulin signaling, the activation of POMC
      neurons by insulin and the insulin-induced and POMC-mediated repression of HGP.
      Our findings define a molecular mechanism for integrating POMC neural responses
      with feeding to control glucose metabolism.

PMID- 30230474
TI  - Substance use patterns and HIV-1 RNA viral load rebound among HIV-positive
      illicit drug users in a Canadian setting.
AB  - BACKGROUND: Active illicit drug use can present a barrier to the medical
      management of HIV infection by complicating adherence to antiretroviral therapy
      (ART). Plasma HIV-1 RNA viral load (VL) rebound, defined as a period of
      detectable HIV viral load (VL) following antiretroviral therapy (ART) and VL
      suppression, can lead to the generation of viral resistance and potential
      treatment failure. We sought to investigate the contribution of substance use
      patterns on rates of VL rebound. METHODS: We used data from the ACCESS study, a
      long-running community-recruited prospective cohort of HIV-positive people who
      use illicit drugs in Vancouver, Canada, a setting of universal no-cost HIV
      treatment. We analyzed time to VL rebound (i.e., two consecutive observations >=
      1000 copies/mL) after ART initiation and sustained viral suppression (i.e., two
      consecutive observations < 50 c/mL) using extended Cox regression models with a
      recurrent events framework. RESULTS: Between May 1996 and November 2013, 564 ART
      exposed participants achieved at least one instance of viral load suppression and
      contributed 1893.8 person-years of observation. Over follow-up, 198 (35.1%)
      participants experienced >= 1 instance of VL rebound. In adjusted analyses, VL
      rebound was associated with younger age (Adjusted Hazard Ratio = 0.97, 95%
      Confidence Interval: 0.95, 0.98), heroin injection (>= daily vs. < daily, AHR =
      1.52, 95% CI: 1.01, 2.30), crack use (>= daily vs. < daily, AHR = 1.73, 95% 1.08,
      1.92) and heavy alcohol use (>= 4 vs. < 4 drinks/day, AHR = 1.97, 95% CI: 1.17,
      3.31). CONCLUSIONS: The present study suggests that in addition to heavy alcohol
      use, high-intensity illicit drug use, particularly >=daily heroin injection and
      >=daily crack smoking are risk factors for VL rebound. In addition to the impact
      of high-intensity drug use on healthcare engagement and ART adherence, some
      evidence exists on the direct impact of psychoactive substances on ART metabolism
      and the natural progression of HIV disease. At-risk individuals should be
      provided additional supports to preserve virologic control and maintain the
      benefits of ART.

PMID- 30230475
TI  - Treatment plan complexity does not predict IROC Houston anthropomorphic head and
      neck phantom performance.
AB  - Previous works indicate that intensity-modulated radiotherapy (IMRT) and
      volumetric modulated arc therapy (VMAT) plans that are highly complex may produce
      more errors in dose calculation and treatment delivery. Multiple complexity
      metrics have been proposed and associated with IMRT QA results, but their
      relationships with plan performance using in situ dose measurements have not been
      thoroughly investigated. This study aimed to evaluate the relationships between
      IMRT treatment plan complexity and anthropomorphic phantom performance in order
      to assess the extent to which plan complexity is related to dosimetric
      performance in the IROC phantom credentialing program. Sixteen complexity
      metrics, including the modulation complexity score (MCS), several modulation
      indices, and total monitor units (MU) delivered, were evaluated for 343 head and
      neck phantom irradiations, comprising both IMRT (step-and-shoot and sliding
      window techniques) and VMAT. Spearman's correlations were used to explore the
      relationship between complexity and plan performance, as measured by the
      dosimetric differences between the treatment planning system (TPS) and
      thermoluminescent dosimeter (TLD) measurement, as well as film gamma analysis.
      Relationships were likewise determined for several combinations of
      subpopulations, based on the linear accelerator model, TPS used, and delivery
      modality. Evaluation of the complexity metrics presented here yielded no
      significant relationships (p  >  0.01, Bonferroni-corrected) and all correlations
      were weak (less than  +/-0.30). These results indicate that complexity metrics
      have limited predictive utility in assessing plan performance in multi
      institutional comparisons of IMRT plans. Other factors affecting plan accuracy,
      such as dosimetric modeling or multileaf collimator (MLC) performance, should be
      investigated to determine a more probable cause for dose delivery errors.

PMID- 30230473
TI  - Condensin controls cellular RNA levels through the accurate segregation of
      chromosomes instead of directly regulating transcription.
AB  - Condensins are genome organisers that shape chromosomes and promote their
      accurate transmission. Several studies have also implicated condensins in gene
      expression, although any mechanisms have remained enigmatic. Here, we report on
      the role of condensin in gene expression in fission and budding yeasts. In
      contrast to previous studies, we provide compelling evidence that condensin plays
      no direct role in the maintenance of the transcriptome, neither during interphase
      nor during mitosis. We further show that the changes in gene expression in post
      mitotic fission yeast cells that result from condensin inactivation are largely a
      consequence of chromosome missegregation during anaphase, which notably depletes
      the RNA-exosome from daughter cells. Crucially, preventing karyotype
      abnormalities in daughter cells restores a normal transcriptome despite condensin
      inactivation. Thus, chromosome instability, rather than a direct role of
      condensin in the transcription process, changes gene expression. This knowledge
      challenges the concept of gene regulation by canonical condensin complexes.

PMID- 30230476
TI  - Symbolic dynamics to enhance diagnostic ability of portable oximetry from the
      phone oximeter in the detection of paediatric sleep apnoea.
AB  - OBJECTIVE: This study is aimed at assessing symbolic dynamics as a reliable
      technique to characterise complex fluctuations of portable oximetry in the
      context of automated detection of childhood obstructive sleep apnoea-hypopnoea
      syndrome (OSAHS). APPROACH: Nocturnal oximetry signals from 142 children with
      suspected OSAHS were acquired using the Phone Oximeter: a portable device that
      integrates a pulse oximeter with a smartphone. An apnoea-hypopnoea index (AHI)
      >=5 events/h from simultaneous in-lab polysomnography was used to confirm
      moderate-to-severe childhood OSAHS. Symbolic dynamics was used to parameterise
      non-linear changes in the overnight oximetry profile. Conventional indices,
      anthropometric measures, and time-domain linear statistics were also considered.
      Forward stepwise logistic regression was used to obtain an optimum feature
      subset. Logistic regression (LR) was used to identify children with moderate-to
      severe OSAHS. MAIN RESULTS: The histogram of 3-symbol words from symbolic
      dynamics showed significant differences (p <0.01) between children with AHI <5
      events/h and moderate-to-severe patients (AHI >=5 events/h). Words representing
      increasing oximetry values after apnoeic events (re-saturations) showed relevant
      diagnostic information. Regarding the performance of individual characterization
      approaches, the LR model composed of features from symbolic dynamics alone
      reached a maximum performance of 78.4% accuracy (65.2% sensitivity; 86.8%
      specificity) and 0.83 area under the ROC curve (AUC). The classification
      performance improved combining all features. The optimum model from feature
      selection achieved 83.3% accuracy (73.5% sensitivity; 89.5% specificity) and 0.89
      AUC, significantly (p-value <0.01) outperforming the other models. SIGNIFICANCE:
      Symbolic dynamics provides complementary information to conventional oximetry
      analysis enabling reliable detection of moderate-to-severe paediatric OSAHS from
      portable oximetry.

PMID- 30230477
TI  - Protective Effects of Oleuropein Against Cerebral Ischemia/Reperfusion by
      Inhibiting Neuronal Apoptosis.
AB  - BACKGROUND In this study, we investigated the potential neuroprotective effect of
      oleuropein (OLE) on apoptotic changes via modulating Akt/glycogen synthase kinase
      3 beta (Akt/GSK-3b) signaling in a rat model of cerebral ischemia/reperfusion
      injury (IRI). MATERIAL AND METHODS Sprague-Dawley male rats (12 weeks, n=200)
      were randomly assigned to 5 groups: sham group, vehicle (IRI+ vehicle) group, OLE
      (IRI+OLE) group, OLE+LY294002 (IRI+OLE+LY294002) group, and
      LY294002(IRI+LY294002) group. The rats were subjected to cerebral
      ischemia/reperfusion injury (IRI) model and treated once daily for 5 days with
      vehicle and OLE (100 mg/kg via intraperitoneal injection) after IRI injury.
      LY294002 (0.3 mg/kg) was intraperitoneally injected once at 30 min after IRI
      injury. Brain edema, neurological deficit, rotarod latencies, and Morris water
      maze (MWM) performance were evaluated after IRI. The number of dead cells were
      assayed by TUNEL staining. Western blot was used to detect the expression of Bcl
      2, Bax, cleaved caspase-3 (CC3), neurotrophic factors, and the phosphorylation
      levels of Akt and GSK-3beta. RESULTS Compared with the vehicle group, brain water
      content, neurological deficits, rotarod latencies, and escape latency following
      IRI were reduced in the OLE group. Cell apoptosis and reduced neurotrophic factor
      caused by IRI was also attenuated by OLE. Furthermore, increased p-Akt and
      decreased p-GSK-3beta were caused by OLE, which were associated with decrease of
      Bax/Bcl-2 ratio and the suppression of Caspase-3 activity after IRI. Importantly,
      all the beneficial effects of OLE in the vehicle group were abrogated by PI3K
      inhibitor LY294002. CONCLUSIONS Cerebral ischemia was protected by OLE via
      suppressing apoptosis through the Akt/GSK-3beta pathway and upregulating
      neurotrophic factor after IRI.

PMID- 30230478
TI  - Hydrogen peroxide production via a redox reaction of N,N'-dimethyl-2,6-diaza-9,10
      anthraquinonediium by addition of bisulfite.
AB  - We demonstrate that bisulfite can be used for reduction of a highly electrophilic
      anthraquinone derivative, N,N'-dimethyl-2,6-diaza-9,10-anthraquinonediium (DAAQ),
      and subsequent autoxidation generates an equivalent of hydrogen peroxide. The
      mechanism for DAAQ reduction by bisulfite, DAAQ electrochemistry, and use of a
      simple test strip assay for H2O2, are described.

PMID- 30230479
TI  - A ratiometric photoelectrochemical immunosensor based on g-C3N4@TiO2 NTs
      amplified by signal antibodies-Co3O4 nanoparticle conjugates.
AB  - Herein, we report a ratiometric photoelectrochemical (PEC) immunosensor coupled
      with secondary antibodies-Co3O4 nanoparticle conjugates (Ab2-Co3O4 NPs) for
      signal amplification. The Ab1-g-C3N4@TiO2 NTs and BSA-g-C3N4@TiO2 NTs act as the
      sensing and reference photoelectrodes, where Ab1, BSA and TiO2 NTs are the
      capture antibodies, bovine serum albumin and TiO2 nanotube arrays, respectively.
      In the presence of target Ag, the sensing PEC photocurrent decreases due to the
      steric hindrance of Ab1 molecules, which increases the inner resistance of the
      photoelectrode. The signal-off response is enhanced further using Ab2-Co3O4 NP
      conjugates due to their steric hindrance effect and the consumption of electron
      donors by the Co3O4 NPs. Furthermore, the performance of the ratiometric PEC
      platform is tested using alpha-fetoprotein (AFP) as a model antigen. Under the
      optimal conditions, the concentration of AFP is detected in the range of 0.4 pg
      mL-1 to 40 ng mL-1 with a detection limit of 0.2 pg mL-1. This ratiometric
      strategy is beneficial to improve the reliability and anti-interference ability
      of PEC immunosensors.

PMID- 30230480
TI  - A new tetra-Zr(iv)-substituted polyoxotungstate aggregate.
AB  - A new tetra-Zr-substituted tungstophosphate (TP),
      [H2N(CH3)2]6Na6H8{Zr2[SbP2W4(OH)2O21][alpha2-PW10O38]}2.50H2O (1), has been made
      by the hydrothermal reaction of the [B-alpha-SbW9O33]9- building block with Zr4+
      cations and PO43- anions in the presence of dimethylamine hydrochloride and NaOAc
      HOAc (pH = 4.8), and further characterized by IR spectroscopy, elemental
      analysis, thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), 31P
      NMR spectroscopy and single-crystal X-ray diffraction. 1 is a toroidal structure
      formed by two divacant [alpha2-PW10O38]11- units and two [SbP2W4(OH)2O21]7-
      fragments linked by four Zr4+ cations. Note that the TP is reassembled with
      tetrahedral PO4 replacing the triangular pyramidal SbO3 in the [B-alpha-SbW9O33]9
      precursor. In addition, the pendant SbO3 derives from the dissociation of the [B
      alpha-SbW9O33]9- precursor. Furthermore, the electrochemical properties of 1 have
      been studied in Na2SO4 + H2SO4 supporting electrolyte (0.5 mol L-1), and indicate
      that 1 exhibits apparent catalytic activity toward H2O2 and BrO3- reduction. The
      31P NMR spectrum of 1 exhibits three signals with approximately proportional
      intensities, which is consistent with the solid-state structure.

PMID- 30230481
TI  - Exploring (bio)catalytic activities of structurally characterised Cu(ii) and
      Mn(iii) complexes: histidine recognition and photocatalytic application of Cu(ii)
      complex and derived CuO nano-cubes.
AB  - Structurally characterised two polymeric complexes of Cu(ii) (3) and Mn(iii) (4)
      of the ligand L (2-(((2-(phenylamino)ethyl)imino)methyl)phenol) have been
      explored for catecholase-like activity, fluorescence recognition of histidine and
      catalytic activity towards coupling of aryl iodides with benzamide, leading to N
      arylbenzamides. CuO nano-cubes (NCs) prepared by thermal decomposition of the
      Cu(ii) complex function as photocatalysts for the degradation of methylene blue.
      Cube-like morphology of CuO nanocrystal and flake-shaped micrometer order Cu(ii)
      complex have been established from the field emissive scanning electron
      microscopy (FESEM) images.

PMID- 30230482
TI  - Anchoring of carboxyl-functionalized porphyrins on MgO, TiO2, and Co3O4
      nanoparticles.
AB  - Hybrid materials consisting of functional organic molecules on metal oxide
      nanomaterials are key components in emerging technologies, for example in energy
      conversion and molecular electronics. In this work, we present the results of a
      comparative study of carboxyl-functionalized porphyrins on different oxide
      nanomaterials. Specifically, we investigated the interaction of 5(3
      carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin (2H-3-MCTPP) and 5(4
      carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin (2H-4-MCTPP), on MgO, TiO2,
      and Co3O4 nanoparticles (NPs) using isothermal and temperature-programmed diffuse
      reflection infrared Fourier transform spectroscopy (DRIFTS). We show that both
      porphyrins bind to the NPs, yielding stable monolayer films consisting of tilted
      surface carboxylates. In all cases, anchoring through the carboxylic acid group
      suppresses self-metalation of the porphyrin unit. Upon annealing, all anchored
      porphyrin films undergo metalation. The position of the acid group has no major
      influence on the reactivity. The same is true for the nature of the metal oxide,
      suggesting that the observed behaviour is general for most anchored porphyrin
      films on oxide nanomaterials.

PMID- 30230483
TI  - Dual conical shell illumination for volumetric high-energy X-ray diffraction
      imaging.
AB  - To retrieve crystallographic information from extended sample volumes requires a
      high-energy probe. The use of X-rays to combine imaging with materials
      characterisation is well-established. However, if fundamental crystallographic
      parameters are required, then the collection and analysis of X-rays diffracted by
      the inspected samples are prerequisites. We present a new X-ray diffraction
      imaging architecture, which in comparison with previous depth-resolving hollow
      beam techniques requires significantly less X-ray power or alternatively supports
      significantly increased scanning speeds. Our conceptual configuration employs a
      pair of conical shell X-ray beams derived from a single point source to
      illuminate extended samples. Diffracted flux measurements would then be obtained
      using a pair of energy resolving point detectors. This dual beam configuration is
      tested using a single X-ray beam set-up employing a dual scan. The use of
      commercial off-the-shelf low-cost components has the potential to provide rapid
      and cost-effective performance in areas including industrial process control,
      medical imaging and explosives detection.

PMID- 30230484
TI  - Supramolecular self-assembly for designing non-centrosymmetric crystals based on
      Keggin polyoxometallates and crown ether.
AB  - We report the synthesis of five novel crystals [(4-BrAni+)(DB[18]crown
      6)]2[SMo12O402-].2CH3CN (1), [(4-BrAni+)(B[18]crown-6)]2[SMo12O402-].CH3CN (2),
      [(4-BrAni+)(B[18]crown-6)]3[PMo12O402-].2CH3CN (3), [(3-AP+)3(B[18]crown
      6)2][PMo12O403-] (4) and [NBu4+][(3-AP2+)(DB[30]crown-10)][PMo12O403-].CH3CN (5)
      (4-BrAni+ = 4-bromoanilinium; B[18]crown-6 = benzo[18]-crown-6; DB[18]crown-6 =
      dibenzo[18]-crown-6; DB[30]crown-10 = dibenzo[30]-crown-10; 3-AP+ = 3
      aminopyridinium; 3-AP2+ = 3-ammoniumpyridinium; NBu4+ = tetrabutylammonium). In
      order to construct non-centrosymmetric crystals, the five crystals were designed
      using a method to gradually introduce asymmetry into the building units. Crystal
      1 was constructed with a symmetric supramolecular cation (SPC) [(4
      BrAni+)(DB[18]crown-6)], resulting in a P21/n space group. The asymmetric SPC [(4
      BrAni+)(B[18]crown-6)] was introduced into [SMo12O402-] to obtain crystal 2,
      which belongs to the symmetric P1[combining macron] space group. Introducing
      trivalent [PMo12O403-], [(4-BrAni+)(B[18]crown-6)] produced crystal 3 with a non
      centrosymmetric Pc space group. The asymmetric sandwich SPC [(3-AP+)3(B[18]crown
      6)2] was designed with multiple hydrogen bonding sites on the 3-AP+ cation, and
      crystal 4 was obtained with trivalent [PMo12O403-]. Crystal 4 has the properties
      of the chiral P1 space group. The distorted SPC (3-AP2+)(DB[30]crown-10) was
      constructed using flexible DB[30]crown-10, resulting in crystal 5 which matched
      the chiral P21 space group with trivalent [PMo12O403-]. This work focuses on
      strategies for the rational design of novel non-centrosymmetric crystals without
      a chiral synthon.

PMID- 30230486
TI  - Binding of halogens by a Cr8 metallacrown.
AB  - A Cr8 metallacrown binds halogens X2 (Cl2, Br2 and I2) without loss of
      crystallinity; the binding has been studied by X-ray diffraction and
      thermodynamic techniques.

PMID- 30230487
TI  - Cu(i) vs. Ru(ii) photosensitizers: elucidation of electron transfer processes
      within a series of structurally related complexes containing an extended pi
      system.
AB  - Heteroleptic Cu(i) complexes are a promising alternative towards traditional
      Ru(ii) photosensitizers. In particular, Cu(i) complexes of the type
      [Cu(P^P)(N^N)]+, where N^N represents a diimine and P^P a bulky diphosphine
      ligand, are already successfully applied for photocatalysis, organic light
      emitting diodes or dye-sensitized solar cells. Therefore, this study aims for the
      systematic comparison of three novel heteroleptic Cu(i) compounds, composed of
      xantphos (xant) as P^P ligand and different diimine ligands with an extended pi
      system in the backbone, with their structurally related Ru(ii) analogues. In
      these Ru(ii) photosensitizers [Ru(bpy)2(N^N)]2+ (bpy = 2,2'-bipyridine) the same
      N^N ligands were used, namely, dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) and
      dipyrido[3,2-a:2',3'-c]phenazine (dppz). To gain an in-depth understanding of the
      photoinduced charge transfer processes, the photophysical features of these
      complexes and their electrochemically oxidized/reduced species were studied by a
      combination of UV-vis absorption, resonance Raman and spectroelectrochemistry.
      (TD)DFT calculations were applied to qualitatively analyze these measurements. As
      a result, the heteroleptic Cu(i) complexes exhibit comparable charge transfer
      properties to their Ru(ii) analogues, i.e. upon visible light excitation they
      undergo a metal-to-ligand charge transfer to the diimine ligand(s). In contrast,
      the reduced Cu(i)- and Ru(ii)-dppz complexes show considerably different
      electronic transitions. The singly reduced Cu(i)-dppz complexes are able to
      accumulate an additional electron at the phenanthroline moiety upon blue-light
      excitation, which is beneficial for multi-electron-transfer reactions. Upon low
      energy light irradiation electronic transitions from the dppz- anion to the xant
      ligand are excited, which could shorten the lifetime of the photosensitizer
      intermediates in an unwanted way.

PMID- 30230488
TI  - Multiple pulse coherent dynamics and wave packet control of the N2 a'' 1Sigma
      dark state by attosecond four-wave mixing.
AB  - Nonlinear multidimensional spectroscopy is ubiquitous in the optical and radio
      frequency regions as a powerful tool to access structure and dynamics. The
      extension of this technique into the extreme ultraviolet (XUV) region with
      attosecond pulses holds promise for probing electronic dynamics and correlations
      with unprecedented time and spatial resolution. In this work, we use noncollinear
      four-wave mixing of a weak XUV attosecond pulse train (11-17 eV) and few
      femtosecond NIR pulses (800 nm) to spectroscopically and dynamically probe the
      dipole-forbidden double-well potential of the a'' 1?+g electronic state of
      nitrogen. The results demonstrate optical coupling of the inner and outer limits
      of the initial XUV-prepared vibrational wave packet in the valence character b'
      1?+u state to the inner and outer wells, respectively, of the a'' 1?+g double
      well state by 800 nm light. Two four-wave mixing schemes with different pulse
      timing sequences and noncollinear beam geometries are used (one NIR pulse
      collinear and one NIR pulse noncollinear versus both NIR pulses noncollinear to
      the XUV beam) to measure the a'' dark state energetic structure and to control
      the dynamical preparation and motion of a dark state wave packet by selective
      population of either the inner Rydberg or outer valence-character potential well.
      Experimental measurements of the a'' 1?+g outer well vibrational spacing and
      anharmonicity closely match the values theoretically predicted for this
      previously unobserved state.

PMID- 30230489
TI  - Structure modulation from unstable to stable MOFs by regulating secondary N-donor
      ligands.
AB  - Four new Zn(ii)/Cd(ii)-based metal-organic frameworks (MOFs), namely
      {[Cd(tmdb)(bib)0.5].solvents}n (YZ-7, YZ stands for the initials of the author
      Yong-Zheng Zhang), {[Cd(tmdb)(bmib)0.5].solvents}n (YZ-8),
      {[Zn2(tmdb)2(bmib)].solvents}n (YZ-9) and {[Zn2(tmdb)2(bmip)2].solvents}n (YZ-10)
      have been solvothermally synthesized by using a semi-rigid ligand, 4,4'-(H-1,2,4
      triazol-1-yl)methylene-dibenzoic acid (H2tmdb), and a series of secondary bis
      imidazole ligands (bib = 1,4-bis(1H-imidazol-1-yl)benzene, bmib = 1,4-bis(2
      methyl-1H-imidazol-1-yl)benzene, and bmip = 1,3-bis(2-methyl-1H-imidazol-1
      yl)propane). By tuning the flexibility of the auxiliary ligands, these MOFs could
      be modulated from unstable (YZ-7-YZ-9) to stable (YZ-10) frameworks. Therefore,
      the gas adsorption properties of YZ-10 are further studied. Interestingly, it
      shows excellent CO2 selective uptake over CH4 and N2. At 298 K, both
      selectivities of CO2/CH4 and CO2/N2 show increasing trends and significantly
      reach 133.2 and 19.9 at 1 atm, respectively. Also, YZ-10 shows uncommon H2
      selective uptake over N2 at 77 K. Moreover, the luminescence properties of YZ-8
      YZ-10 were studied in the solid state at room temperature.

PMID- 30230490
TI  - Using chromate to investigate the impact of mineral-organic contact time on the
      surface reactivity of goethite.
AB  - Chromate was used as a chemical probe to investigate the impact of mineral
      organic contact time on the surface reactivity of two different sizes of goethite
      particles. A series of goethite-chromate sorption batch reactions were conducted
      in the presence and absence of Suwannee River humic acid (HA) and natural organic
      matter (NOM) using nano- and micro-scale goethite particles. In experiments with
      added organics the amount of time allowed for goethite-organic matter interaction
      (i.e. contact time) was varied from less than 1 minute, up to 24 hours prior to
      the addition of chromate. Results indicated that nano- and micro-scale goethite
      in the absence of organics sorbed nearly identical amounts of chromate on a per
      mass basis, despite the greater surface area of the smaller particles. Results
      also indicated that the presence of ~10 mg L-1 of HA and a contact time of less
      than 1 minute reduced the amount of chromate sorbed by both nano- and micro-scale
      goethite. Increasing the contact time resulted in greater decreases in chromate
      sorption. Experiments using NOM produced similar results. While chromate sorption
      was most rapid during the first hour of the experiments, goethite particles
      continued to sorb additional chromate over a period of up to 7 days.
      Additionally, a noticeable impact on chromate sorption due to increased contact
      time was present over that time period.

PMID- 30230491
TI  - Processes at nanopores and bio-nanointerfaces: general discussion.

PMID- 30230493
TI  - Enantio- and regioselective ene-reductions using F420H2-dependent enzymes.
AB  - In the past decade it has become clear that many microbes harbor enzymes that
      employ an unusual flavin cofactor, the F420 deazaflavin cofactor. Herein we show
      that F420-dependent reductases (FDRs) can successfully perform enantio-, regio-
      and chemoselective ene-reductions. For the first time, we have demonstrated that
      F420H2-driven reductases can be used as biocatalysts for the reduction of
      alpha,beta-unsaturated ketones and aldehydes with good conversions (>99%) and
      excellent regioselectivities and enantiomeric excesses (>99% ee). Noteworthily,
      FDRs typically display an opposite enantioselectivity when compared to the well
      established FMN-dependent Old Yellow Enzymes (OYEs).

PMID- 30230495
TI  - Ab initio instanton rate theory made efficient using Gaussian process regression.
AB  - Ab initio instanton rate theory is a computational method for rigorously
      including tunnelling effects into the calculations of chemical reaction rates
      based on a potential-energy surface computed on the fly from electronic-structure
      theory. This approach is necessary to extend conventional transition-state theory
      into the deep-tunnelling regime, but it is also more computationally expensive as
      it requires many more ab initio calculations. We propose an approach which uses
      Gaussian process regression to fit the potential-energy surface locally around
      the dominant tunnelling pathway. The method can be converged to give the same
      result as from an on-the-fly ab initio instanton calculation but it requires far
      fewer electronic-structure calculations. This makes it a practical approach for
      obtaining accurate rate constants based on high-level electronic-structure
      methods. We show fast convergence to reproduce benchmark H + CH4 results and
      evaluate new low-temperature rates of H + C2H6 in full dimensionality at a
      UCCSD(T)-F12b/cc-pVTZ-F12 level.

PMID- 30230496
TI  - On the consequences of the stereochemical activity of the Bi(iii) 6s2 lone pair
      in cyclen-based complexes. The [Bi(DO3A)] case.
AB  - We report a detailed study of the structure of the [Bi(DO3A)] complex both in the
      solid state and in solution. The X-ray crystal structure of [Bi(DO3A)] evidences
      the octa-coordination of the Bi(iii) ion, which is directly coordinated to the
      four nitrogen atoms of the cyclen unit and three oxygen atoms of the carboxylate
      groups. The octa-coordination is completed by an oxygen atom of a neighboring
      carboxylate group, which bridges Bi(iii) ions thanks to MU2-eta1:eta1
      coordination, resulting in the formation of a coordination polymer. The Bi(iii)
      ion presents a twisted-square antiprismatic (TSAP) coordination geometry
      associated with the Delta(deltadeltadeltadelta)/Lambda(lambdalambdalambdalambda)
      enantiomeric pair. A computational DFT study indicates that the 6s2 lone pair of
      Bi(iii) is stereochemically active in [Bi(DO3A)] and most of the cyclen-based
      complexes reported in the literature. Depending on the spatial arrangement of the
      donor atoms of the ligand the lone pair points in different directions, so that
      Bi(iii) can easily accommodate different coordination environments. In solution
      the [Bi(DO3A)] complex exists as a monomeric complex, as demonstrated by DOSY
      measurements. The stability constant of the [Bi(DO3A)] complex, determined by
      using batch spectrophotometric titrations, was found to be rather high (log K =
      26.85(5)). The complex presents characteristic absorption in the UV spectrum at
      299 nm (epsilon = 8770 M-1 cm-1) that was attributed to the Bi(iii)-centered 6p <
      6s band on the basis of TDDFT calculations. Spectrophotometric titrations reveal
      weak binding of different anions to the [Bi(DO3A)] complex, with association
      constants of K11 = 3.55(8), 3.09(7), 6.2(1) and 2.19(5) for Cl-, Br-, I- and N3-,
      respectively.

PMID- 30230497
TI  - Acid induced reduction of the glycaemic response to starch-rich foods: the
      salivary alpha-amylase inhibition hypothesis.
AB  - Numerous studies have reported that the glycaemic response to starch-rich meals
      can be reduced by 20-50% with acidic drinks or foods. A number of candidate
      explanations have been put forward, but this phenomenon still remains vaguely
      understood. This study intends to demonstrate the remarkable effect of acid
      inhibition of salivary alpha-amylase during oro-gastric hydrolysis of starch,
      shedding light on this often overlooked mechanism. Oro-gastric digestions of
      bread, wheat and gluten-free pastas, combined with either water or lemon juice
      were performed using a dynamic in vitro system that reproduces gastric
      acidification kinetics observed in humans. In the presence of water, large
      proportions of starch (25-85%) and oligosaccharides (15-50%) were released from
      all foods within the first hour of gastric digestion (pH > 3.5). In the presence
      of lemon juice (pH < 3.5 at all time), starch release was about twice as low, and
      amylolysis into oligosaccharides was completely interrupted. Acid-inhibition of
      salivary alpha-amylase may explain, at least in part, the reduction of the blood
      glucose response through acidification of starch-rich foods/meals. This offers
      new perspectives for the development of strategies to improve the glycaemic
      response elicited by starch-rich diets.

PMID- 30230501
TI  - Low-temperature nanospectroscopy of the structural ferroelectric phases in single
      crystalline barium titanate.
AB  - We optically investigate the local-scale ferroelectric domain structure of
      tetragonal, orthorhombic, and rhombohedral barium titanate (BTO) single crystals
      using scattering-type scanning near-field infrared (IR) optical microscopy (s
      SNIM) at temperatures down to 150 K. Thanks to the precisely tunable narrow-band
      free-electron laser FELBE, we are able to explore the spectral fingerprints and
      IR resonances of these three phases and their domain orientations in the optical
      IR near-field. More clearly, every structural phase is analyzed with respect to
      its near-field resonances close to a wavelength of 17 MUm when exploring the
      (111)-oriented BTO sample surface. Furthermore, near-field imaging at these
      resonances is performed, that clearly allows for the unambiguous optical
      identification of different domain orientations. Since our s-SNIM is based on a
      non-contact scanning force microscope, our s-SNIM findings are backed up by
      sample-topography and piezoresponse force microscopy (PFM) imaging, providing
      complementary information in an excellent match to the s-SNIM results.

PMID- 30230498
TI  - Processes at nanoelectrodes: general discussion.

PMID- 30230504
TI  - Tryptophol and derivatives: natural occurrence and applications to the synthesis
      of bioactive compounds.
AB  - Covering: up to 2018Tryptophol (indole-3-ethanol) is a metabolite produced by
      plants, bacteria, fungi and sponges. This review reports on the natural
      occurrence, bioactivity and various synthetic approaches to the preparation of
      tryptophol and its derivatives. Syntheses of various naturally occurring
      tryptophol derivatives known for their enhanced pharmacological profile are also
      presented.

PMID- 30230508
TI  - Phase diagrams of mixtures of dipolar rods and discs.
AB  - Self-assembly of binary mixtures that contain anisotropic, interacting colloidal
      particles have been proposed as a way to create new, multi-functional materials.
      We simulate binary mixtures of dipolar rods and dipolar discs in two-dimensions
      using discontinuous molecular dynamics to determine how the assembled structures
      of these mixtures differ from those seen in single component systems. Two
      different binary mixtures are investigated: a mixture of an equal number of
      dipolar rods and dipolar discs ("equal number"), and a mixture where the area
      fraction of dipolar rods is equal to the area fraction of dipolar discs ("equal
      area"). Phase boundaries between fluid, string-fluid, and "gel" phases are
      calculated and compared to the phase boundaries of the pure components. Looking
      deeper at the underlying structure of the mixture reveals a complex interplay
      between the rods and discs and the formation of states where the two components
      are in different phases. The mixtures exhibit phases where both rods and discs
      are in the fluid phase, where rods form a string-fluid while discs remain in the
      fluid phase, a rod string-fluid coexisting with a disc string-fluid, a "gel" that
      consists primarily of rods while the discs form either a fluid or string-fluid
      phase, and a "gel" that contains both rods and discs. Our results give insight
      into the general assembly pathway of binary mixtures, and how complex aggregates
      can be created by varying the mixture composition, strength of interaction
      between the two components, and the temperature. By manipulating the properties
      of one of the components it should be possible to fabricate bifunctional,
      thermally responsive self-assembled materials.

PMID- 30230509
TI  - Phase separation around a heated colloid in bulk and under confinement.
AB  - We study the non-equilibrium coarsening dynamics of a binary liquid solvent
      around a colloidal particle in the presence of a time-dependent temperature
      gradient that emerges after a temperature quench of a suitable coated colloid
      surface. The solvent is maintained at its critical concentration and the colloid
      is fixed in space. The coarsening patterns near the surface are shown to be
      strongly dependent on the colloid surface adsorption properties and on the
      temperature evolution. The temperature gradient alters the morphology of the
      binary solvent near the surface of the colloid as compared to the coarsening
      proceeding at a constant temperature everywhere. We also present results for the
      evolution of coarsening in thin films with confining surfaces preferring one
      species of the binary liquid mixture over the other. Confinement leads to a
      faster phase segregation process and formation of a bridge connecting the colloid
      and both confining walls.

PMID- 30230511
TI  - Accurate estimation of the polymer coverage of hairy nanoparticles.
AB  - Understanding and predicting the mechanisms underpinning the self-assembly of
      polymer-grafted nanoparticles (PGNPs) are important for controlling the
      engineering applications of these novel materials. The self-assembly of these
      materials is driven by their surfactancy, i.e., by the fact that the (inorganic)
      nanoparticles energetically dislike the (organic) polymer tethers. In previous
      work we developed a model in which a grafted polymer chain was treated as a rigid
      equivalent sphere (ES) which was impenetrable to the NPs, but completely
      penetrable to other ESs. This description, along with a geometric analogy with
      patchy particles, allowed us to facilely explain the self-assembly of PGNPs.
      However, since we model an ES as being completely penetrable to other ESs but
      impenetrable to the NPs the physical correspondence between a "real" grafted
      polymer and an ES is not clear. The application of the ES model to experiments
      and to computer simulations has therefore seen limited success, and only
      qualitative agreement has been obtained. In this paper, we develop a more
      realistic description, termed the modified ES (mES) model, based on the work of
      Daoud and Cotton on curved polymer brushes, which takes the impenetrability of
      the individual chain monomers into account. While this approach increases the
      complexity of our formalism, we find that the resulting mES model quantitatively
      captures computer simulation results on the structure of the PGNPs and also
      quantitatively explains their self-assembly over a broad range of conditions.

PMID- 30230512
TI  - Disseminated Skin Lesions After Allogeneic Hematopietic Stem Cell
      Transplantation.

PMID- 30230513
TI  - In the Literature.

PMID- 30230515
TI  - Research in Gerontological Nursing: How Are We Doing?

PMID- 30230516
TI  - Progress and Changes in Gerontological Nursing Research in the Midwest: A Review.
AB  - Gerontological nursing has a rich research history. The current article reports
      trends in gerontological nursing research found through review of abstracts of
      presentations at the Midwest Nursing Research Society annual conference at 10
      year increments over the 40-year existence of the organization. Researchers
      studied a wide range of topics, from quality of life to use of technology, with a
      variety of older adult populations represented. Designs, theoretical frameworks,
      and other methods mirrored trends in nursing research from 1977 to 2017.
      Gerontological nursing researchers had a strong and sustained presence in the
      Midwest, as evidenced by these abstracts. [Res Gerontol Nurs. 2018; 11(5):231
      237.].

PMID- 30230517
TI  - Psychosocial Factors Associated With Reduced Muscle Mass, Strength, and Function
      in Residential Care Apartment Complex Residents.
AB  - Sarcopenia is a major source of disability in older adults. However, limited data
      are available about sarcopenia components (i.e., muscle mass, strength, and
      function) and their relationship to psychosocial factors among older adults
      living in residential care apartment complexes (RCACs). The current study
      examined muscle mass, strength, and function and explored their relationship to
      self-efficacy for exercise, depressive symptoms, and social support in 31 RCAC
      residents. RCAC residents had lower muscle mass, strength, and function compared
      to values reported in studies of community-dwelling older adults. Men had higher
      muscle mass and strength than women. The current findings showed a trend for
      individuals with high self-efficacy, without depressive symptoms, and with strong
      social support to present numerically greater muscle mass, strength, and
      function. Further studies with larger samples are needed to confirm the current
      study findings and inform development of interventions implemented in RCAC
      settings. [Res Gerontol Nurs. 2018; 11(5):238-248.].

PMID- 30230518
TI  - African American Older Adults' Perceived Use of Technology for Hypertension Self
      Management.
AB  - With the unprecedented growth of technology for disease prevention and
      management, little is known about the experience and adoption of such technology
      in African American older adults with hypertension. A 90-minute focus group
      session was used to explore African American older adults' (N = 21) experiences
      with using technology (mobile devices and applications) for hypertension self
      management. Twenty participants reported owning smartphones and used this
      technology to communicate; seek, acquire, and share information; engage in
      entertainment; and organize and manage time. Participants expressed concerns
      about not being informed or trained sufficiently to integrate technology for
      hypertension self-management. There is a need to develop novel hypertension self
      management interventions that integrate technology and training programs for this
      marginalized population that may help improve blood pressure control and address
      important clinical and public health priorities of uncontrolled hypertension.
      [Res Gerontol Nurs. 2018; 11(5):249-256.].

PMID- 30230519
TI  - Effects of Pain and Sleep Quality on Falls Among Nursing Home Residents in
      Turkey.
AB  - The current study was conducted to detect the incidence of falls among
      individuals in nursing homes, as well as the impact of pain and sleep quality on
      falls. The sample for this cross-sectional study comprised 291 older adults. Pain
      was assessed using the Geriatric Pain Measure and insomnia was assessed using the
      Insomnia Severity Index. Incidence of falls within the past 1 year was 40.9%.
      Risk factors for falling were determined using logistic regression analysis.
      Based on the analysis, being single (odds ratio [OR] = 2.502, 95% confidence
      interval [CI] [1.155, 6.195]) and experiencing pain (OR = 2.841, 95% CI [1.195
      6.754]) were risk factors for falling. In the current study, falling was seen as
      a common problem among older adults. Pain in particular should be addressed when
      planning the prevention of falls in nursing homes. [Res Gerontol Nurs. 2018;
      11(5):257-264.].

PMID- 30230520
TI  - Formal home care use in Canada.
AB  - BACKGROUND: Formal home care services (those typically delivered by health care
      providers or volunteer organizations) are different from informal home care
      services (given by family, friends or neighbours), and thus represent a partial
      picture of all home care provided. Home care has been associated with decreased
      mortality, improved quality of life, and reduced hospitalizations and health care
      costs. DATA AND METHODS: New data from the annual Canadian Community Health
      Survey (CCHS) 2015/2016 are used to estimate, for the first time, the number and
      percentage of households in which at least one person of any age received formal
      home care services in Canada during the previous year. A descriptive analysis of
      socioeconomic characteristics of households receiving formal home care is
      presented. RESULTS: An estimated 6.4% of households (881,800) in Canada received
      formal home care services in the past year, most frequently nursing (46%) and
      personal/home support services (46%). Households with parents and adult children
      (age 25 or older), one-person households, and households with lower socioeconomic
      status were most likely to have received formal home care. Costs were covered by
      a range of sources. They were paid solely by government (52%), solely out of
      pocket (27%), solely by insurance (7%), at least partially by insurance and/or
      government (8%), and by other sources (6%). Households that received home health
      care services only-particularly nursing services-were more likely to have their
      costs entirely covered by government, while those that received support services
      only were more likely to pay out-of-pocket costs. DISCUSSION: This descriptive
      analysis of household use of formal home care services by socioeconomic
      characteristics and type of care will help inform health care policies and
      programs. Future person-level analysis can examine the independent factors
      associated with home care use.

PMID- 30230521
TI  - Progress in net cancer survival in Canada over 20 years.
AB  - BACKGROUND: Monitoring the progress of cancer survival in a population over time
      is an important part of cancer surveillance. DATA AND METHODS: Data are from the
      Canadian Cancer Registry with mortality follow-up through record linkage to the
      Canadian Vital Statistics Death Database and tax files. Net survival (NS) was
      derived using the Pohar Perme method. Predicted estimates of NS for the period
      from 2012 to 2014 were calculated using the period method. Age-standardized and
      age-specific changes in five-year NS between the periods from 1992 to 1994 and
      2012 to 2014 were determined for 30 individual cancers. RESULTS: Predicted five
      year NS for 2012 to 2014 ranged from 98% for thyroid cancer to 7% for
      mesothelioma. Between 1992 to 1994 and 2012 to 2014, improvements in five-year
      age standardized NS were greatest for chronic myeloid leukemia (23.9 percentage
      points), though a large majority of the increase occurred in the first decade.
      Increases exceeding 15.0 percentage points were also observed for non-Hodgkin
      lymphoma (19.5), cancer of the small intestine (17.4) and multiple myeloma
      (16.9). In contrast, little to no improvement was observed for cancers of the
      anus, larynx, soft tissue or uterus, or for mesothelioma. Increases in five-year
      NS were greatest for chronic myeloid leukemia in each age group with the
      exception of those aged 75 to 84 years (thyroid). DISCUSSION: This study reveals
      important areas of progress in cancer outcomes in Canada since the early 1990s.
      It also sheds light on cancers for which there has seemingly been no improvement
      in five-year net survival over a 20-year period.

PMID- 30230523
TI  - The PRISM intervention for adolescents and young adults with cancer: Paying
      attention to the patient as a whole person.

PMID- 30230525
TI  - Sixth International Symposium on Childhood, Adolescent and Young Adult Non
      Hodgkin Lymphoma Abstracts, 26-29 September 2018, De Doelen International
      Congress Centre, Rotterdam, Netherlands.

PMID- 30230522
TI  - Subtype-specific inherited predisposition to pemphigus in the Chinese population.
AB  - BACKGROUND: Pemphigus is a group of rare life-threatening mucocutaneous
      autoimmune diseases, presenting mainly as two subtypes: pemphigus vulgaris (PV)
      and pemphigus foliaceus (PF). Inherited predispositions to pemphigus have long
      been speculated but they remain poorly understood. OBJECTIVES: To identify common
      and specific nongenetic and genetic factors associated with pemphigus and its
      subtypes in the Chinese population. METHODS: A genome-wide association study
      (GWAS) was performed in 496 unrelated patients with pemphigus (including 365 with
      PV and 104 with PF) and 1105 controls without pemphigus. RESULTS: A sex
      preference was observed only in PV (57.5% female) and not in PF (47.1% female).
      For male patients only, the mean age at diagnosis was significantly lower for PV
      than for PF (P < 0.001). The strongest associated single-nucleotide polymorphisms
      are in the human leucocyte antigen (HLA) region: rs70993900 (PV; P = 1.5 * 10-45
      ) and rs9469220 (PF; P = 1.1 * 10-8 ). HLA-DQB1*05:03 ranks at the top (P = 4.7 *
      10-40 ; odds ratio 12.4) in both subtypes, with significantly different risk
      allele frequency (RAFPV = 34.2% vs. RAFPF = 18.8% vs. RAFcontrol = 4.4%), whereas
      HLA-DRB1*14:01 and HLA-DRB1*04:06 are PV specific. HLA-DQB1*03:03 and HLA
      DQB1*03:02 show significant subtype specificity in opposite directions. All of
      these associations were validated in the replication series with 147 cases of
      pemphigus and 604 controls. Multiple novel non-HLA susceptibility loci were also
      identified in the GWAS. CONCLUSIONS: This study represents the largest GWAS on
      pemphigus in the Chinese population published to date, and has allowed us to
      identify HLA haplotypes significantly shared between or specific to the two main
      subtypes of pemphigus.

PMID- 30230524
TI  - Early-SEPs' amplitude reduction is reliable for poor-outcome prediction after
      cardiac arrest?
AB  - OBJECTIVE: The bilateral absence of cortical Somatosensory Evoked Potentials
      (SEPs), after cardiac arrest (CA), is a high reliable predictor of poor outcome
      but it is present in no more than 40% of patients. An amplitude reduction of
      cortical SEPs was found in about 30% of subjects, but few papers analysed its
      prognostic significance. The aim of our study is to identify a value of SEP
      amplitude reduction below which all the CA patients had poor outcome and the
      relationship between SEP and Electroencephalogram (EEG) patterns. MATERIAL AND
      METHODS: We analysed comatose patients in whom SEPs and EEG were recorded at 6-12
      hours after CA. We evaluated the sensitivity at specificity of 100% of SEP
      amplitude in predicting the non-recovery of consciousness by plotting Receiver
      Operating Characteristic (ROC) curves. We also analysed the relationship between
      SEP amplitude and EEG patterns. Outcome was evaluated at 6 months by Glasgow
      Outcome Scale. RESULTS: We analysed 119 subjects. According to the ROC analysis
      (area under the curve = 0.95/CI 0.91-0.99), all patients with a cortical SEP
      amplitude <0.65 MUV did not recover consciousness (GOS 1-2), with a sensitivity
      of 71.8%. Severe EEG abnormalities (suppression and burst-suppression patterns)
      were also observed in all these patients. CONCLUSION: Not only the absence but
      also a bilateral amplitude reduction of cortical SEPs (<0.65 MUV) is associated
      with ominous prognosis (death or non-recovery of consciousness) with a very high
      predictive value. However, we emphasize that great caution should be applied
      before adopting amplitude reduction as a criterion for the poor prognosis of CA
      patients.

PMID- 30230526
TI  - Direct RIG-I activation in human NK cells induces TRAIL-dependent cytotoxicity
      towards autologous melanoma cells.
AB  - Activation of the innate immune receptor retinoic acid-inducible gene I (RIG-I)
      by its specific ligand 5'-triphosphate RNA (3pRNA) triggers anti-tumor immunity,
      which is dependent on natural killer (NK) cell activation and cytokine induction.
      However, to date, RIG-I expression and the functional consequences of RIG-I
      activation in NK cells have not been examined. Here, we show for the first time
      the expression of RIG-I in human NK cells and their activation upon RIG-I ligand
      (3pRNA) transfection. 3pRNA-activated NK cells killed melanoma cells more
      efficiently than NK cells activated by type I interferon. Stimulation of RIG-I in
      NK cells specifically increased the surface expression of membrane-bound TNF
      related apoptosis-inducing ligand (TRAIL) on NK cells, while activated NK cell
      receptors were not affected. RIG-I-induced membrane-bound TRAIL initiated death
      receptor-pathway-mediated apoptosis not only in allogeneic but also in autologous
      human leukocyte antigen (HLA) class I-positive and HLA class I-negative melanoma
      cells. These results identify the direct activation of RIG-I in NK cells as a
      novel mechanism for how RIG-I can trigger enhanced NK cell killing of tumor
      cells, underscoring the potential of RIG-I activation for tumor immunotherapy.
      This article is protected by copyright. All rights reserved.

PMID- 30230527
TI  - LncRNA CRNDE promotes hepatocellular carcinoma cell proliferation, invasion, and
      migration through regulating miR-203/ BCAT1 axis.
AB  - OBJECTIVE: To investigate the impact of long noncodingRNA (lncRNA) colorectal
      neoplasia differentially expressed (CRNDE) on hepatocellular cancer (HCC) cell
      propagation, invasion, and migration by mediating miR-203/ BCAT1 axis. METHODS:
      Microarray analysis was based on 25 pairs of HCC cancerous tissues and adjacent
      tissues. The expression levels of CRNDE, miR-203, and BCAT1 in HCC tissues were
      analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The liver
      cell line L-02 and HCC cell lines HepG2 and Huh-7 were utilized to assess the
      regulatory effects of CRNDE and miR-203 on HCC progression in vitro. Western blot
      was used to qualify BCAT1 protein expression level. Cell proliferation and
      apoptosis were evaluated using CCK-8 and flow cytometry analysis, whereas cell
      invasion and migration assay were performed by the Transwell assay. The
      relationship among CRNDE, miR-203, and BCAT1 was validated by dual luciferase
      assay. Tumor Xenograft study was established to verify the pathological effect of
      CRNDE on HCC development in vivo. RESULTS: The expression levels of the CRNDE and
      BCAT1 were upregulated in HCC tissues and cells, whereas miR-203 was
      downregulated in HCC. Knockdown of CRNDE or miR-203 overexpression would inhibit
      HCC cell propagation and metastasis, and induced cell apoptosis. Moreover, miR
      203 was negatively correlated with CRNDE, the same as miR-203 with BCAT1. Dual
      luciferase assay showed that miR-203 was an inhibitory target of CRNDE, and BCAT1
      was directly targeted by miR-203 as well. CONCLUSION: LncRNA CRNDE could enhance
      HCC tumorgenesis by sponging miR-203 and mediating BCAT1. LncRNA CRNDE might
      facilitate HCC cell propagation, invasiveness, and migration through regulating
      miR-203/ BCAT1 axis.

PMID- 30230528
TI  - Sertad1 promotes prostate cancer progression through binding androgen receptor
      ligand binding domain.
AB  - Androgen receptor (AR) signaling is involved in the initiation and progression of
      prostate cancer (PCa), which is the most frequently diagnosed nonskin cancer and
      remains a leading cause of cancer-related death in men. Further investigation of
      the involvement of AR signaling in PCa progression is urgently needed. In the
      present study, we performed a yeast two-hybrid screen and demonstrated that SERTA
      domain-containing protein 1 (Sertad1) is a novel AR-binding protein that binds to
      the AR ligand binding domain (LBD). The binding between AR-LBD and Sertad1 was
      confirmed by glutathione S-transferase (GST) pull-down assays and
      immunoprecipitation (IP) and confocal immunofluorescence co-localization
      experiments. Furthermore, we demonstrated that DHT inhibited Sertad1 protein
      degradation in prostate cancer cell lines and that Sertad1 knockdown inhibited
      the proliferation of prostate cancer cells in vitro. In human PCa tumor tissues,
      Sertad1 expression is positively correlated with AR expression and the Gleason
      score. Taken together, this report is the first to show that Sertad1 is a novel
      AR-LBD-binding protein, and DHT-liganded AR-LBD inhibits Sertad1 degradation.
      Thus, Sertad1 may represent a novel therapeutic target for the treatment of AR
      positive PCa.

PMID- 30230529
TI  - What lengths for a lash?

PMID- 30230530
TI  - Exercise interventions to improve balance for young people with intellectual
      disabilities: a systematic review and meta-analysis.
AB  - AIM: To conduct a systematic review and meta-analysis of the effects of exercise
      interventions designed to improve balance in young people with intellectual
      disabilities. METHOD: A systematic literature search was performed on 10
      databases. Studies in press or published in English in a peer-reviewed journal
      were included if: (1) participants were young people with intellectual
      disabilities; (2) exercise interventions were designed to improve balance; and
      (3) they used quasi-experimental or experimental designs. Studies focusing only
      on a specific subpopulation of young people with intellectual disabilities or
      having a specific physical characteristic were excluded. Risk of bias was
      assessed for randomization, allocation sequence concealment, blinding, incomplete
      outcome data, selective outcome reporting, and other biases. RESULTS: The search
      strategy identified 937 articles and 15 studies, published between 1991 and 2017,
      that met the inclusion criteria. Exercise intervention groups showed a
      significant and larger improvement in static (pooled effect size, Hedges' g=0.98)
      and dynamic (g=1.34) balance compared with the control groups. However, although
      the pooled improvement of static-dynamic balance was large (g=2.80), the result
      was non-significant. None of the subgroup analyses were significant, except for
      the improvement in: (1) static balance (higher in quasi-experimental than in
      experimental studies); and (2) dynamic balance (higher in young people with a
      mild vs a mild-moderate intellectual disability). INTERPRETATION: The reviewed
      exercise interventions seem to represent an effective means for improving the
      static and dynamic balance of young people with intellectual disabilities.
      However, the present findings should be considered as preliminary given the small
      number of studies and their limitations. WHAT THIS PAPER ADDS: Exercise
      intervention results in large and significant improvements in static and dynamic
      balance in young people with intellectual disabilities. Exercise intervention
      results in a large but non-significant improvement in static-dynamic balance.
      Static balance improvement was significantly higher in quasi-experimental versus
      experimental studies. Dynamic balance improvement was significantly higher in
      young people with mild versus mild-moderate intellectual disability. No
      significant differences related to age group, balance measures, and components of
      exercise intervention were found.

PMID- 30230531
TI  - Promoting resilience in adolescents and young adults with cancer: Results from
      the PRISM randomized controlled trial.
AB  - BACKGROUND: Adolescents and young adults (AYAs) with cancer are at risk for poor
      psychosocial outcomes. This study aimed to determine whether a novel intervention
      targeting resilience resources would improve patient-reported resilience, quality
      of life, and psychological distress. METHODS: In this parallel, phase 2
      randomized controlled trial, English-speaking AYAs (12-25 years old) with cancer
      were randomized to the Promoting Resilience in Stress Management (PRISM)
      intervention or usual care (UC). PRISM is a brief, skills-based intervention
      targeting stress management, goal setting, cognitive reframing, and meaning
      making. Participants completed surveys at enrollment and 6 months. Mixed effects
      regression models evaluated associations between PRISM and the primary outcome
      (10-item Connor-Davidson Resilience Scale scores) and secondary outcomes (generic
      and cancer-related quality of life [Pediatric Quality of Life modules],
      psychological distress [Kessler-6], and anxiety/depression [Hospital Anxiety and
      Depression]) at 6 months. RESULTS: Ninety-two AYAs were enrolled, were
      randomized, and completed baseline surveys (48 in the PRISM group and 44 in the
      UC group); 73% were 12 to 17 years old, and 62% had leukemia or lymphoma.
      Attrition was primarily due to medical complications and/or death; 36 PRISM
      participants and 38 UC participants completed 6-month surveys. PRISM was
      associated with improved resilience (+3.0 points; 95% confidence interval [CI],
      0.5-5.4; P = .02) and cancer-specific quality of life (+9.6; 95% CI, 2.6-16.7; P
      = .01) and reduced psychological distress (-2.1; 95% CI, -4.1 to -0.2; P = .03)
      but not generic quality of life (+7.2; 95% CI, -0.8 to 15.2; P = .08). Although
      anxiety was similar between the groups, 2 PRISM participants (6%) and 8 UC
      participants (21%) met the criteria for depression at 6 months (odds ratio, 0.09;
      95% CI, 0.01-1.09; P = .06). CONCLUSIONS: PRISM was associated with improved
      psychosocial outcomes in comparison with UC, suggesting that brief, skills-based
      interventions for AYAs may provide a benefit.

PMID- 30230532
TI  - Asking Children to "Be Helpers" Can Backfire After Setbacks.
AB  - Describing behaviors as reflecting categories (e.g., asking children to "be
      helpers") has been found to increase pro-social behavior. The present studies (N
      = 139, ages 4-5) tested whether such effects backfire if children experience
      setbacks while performing category-relevant actions. In Study 1, children were
      asked either to "be helpers" or "to help," and then pretended to complete a
      series of successful scenarios (e.g., pouring milk) and unsuccessful scenarios
      (e.g., spilling milk while trying to pour). After the unsuccessful trials,
      children asked to "be helpers" had more negative attitudes. In Study 2, asking
      children to "be helpers" impeded children's helping behavior after they
      experienced difficulties while trying to help. Implications for how category
      labels shape beliefs and behavior are discussed.

PMID- 30230533
TI  - Linear IgA bullous dermatosis presenting as chronic prurigo: unveiling of the
      diagnosis by serrated pattern analysis.

PMID- 30230534
TI  - Comprehensive transcriptome profiling in elderly cancer patients reveals aging
      altered immune cells and immune checkpoints.
AB  - Aging is the single most significant risk factor for cancer development. However,
      the potential impact of aging on cancer microenvironment remains poorly
      understood. Here, we performed a pan-cancer transcriptome analysis to identify
      aging-specific molecular patterns across 18 cancer types. Strikingly, aging
      specific molecular features define human cancers into two types, including the
      strong and weak aging-effect groups. Significant aging associated molecular
      signature was observed in 16 cancer types (strong aging-effect group) such as
      breast invasive carcinoma and acute myeloid leukemia. In such 16 cancer types,
      old patients showed obvious poor survival compared to young patients, but this
      observation was not found in the weak aging-effect cancers. Aging-associated
      cancer-relevant molecules significantly enriched in 23 pathways including EMT and
      KRAS signaling. More interestingly, in cancer microenvironment, aging
      significantly restrains adaptive immunity, but strikingly, increases the number
      of infiltrated innate immune cells. Further analysis shows that the expression of
      immune checkpoints including PD-1, PD-L1, PD-L2, and CTLA-4 are mostly correlated
      with age. In general, cancer cells in elderly patients show a more aggressive
      phenotype and their surrounding microenvironment is under a more immune
      suppression status compared with young patients. Our study provides a systematic
      understanding of aging-associated molecular features in pan-cancer and indicates
      a clinical requirement to develop aging-specific therapeutic strategies in a
      majority of cancer types. Furthermore, aging-altered immune cells and immune
      checkpoints should be considered in cancer immunotherapy. This article is
      protected by copyright. All rights reserved.

PMID- 30230535
TI  - Onycholysis and subungual purpura of nails.

PMID- 30230536
TI  - Mediterranean diet adherence and risk of pancreatic cancer: A pooled analysis of
      two Dutch cohorts.
AB  - 3w?>Studies investigating the association of Mediterranean diet (MD) adherence
      with pancreatic cancer risk are limited and had inconsistent results. We examined
      the association between MD adherence and pancreatic cancer incidence by pooling
      data from the Netherlands Cohort Study (NLCS, 120,852 subjects) and the Dutch
      cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC
      NL, 40,011 subjects). MD adherence was assessed using alternate and modified
      Mediterranean diet scores (aMED and mMED, respectively), including and excluding
      alcohol. After median follow-ups of 20.3 (NLCS) and 19.2 (EPIC-NL) years, 449
      microscopically confirmed pancreatic cancer (MCPC) cases were included in study
      specific multivariable Cox models. Study-specific estimates were pooled using a
      random-effects model. MD adherence was not significantly associated with MCPC
      risk in pooled and study-specific analyses, regardless of sex and MD score.
      Pooled hazard ratios (95% confidence interval) for high (6-8) compared to low (0
      3) values of mMED excluding alcohol were 0.66 (0.40-1.10) in men and 0.94 (0.63
      1.40) in women. In never smokers, mMED excluding alcohol seemed to be inversely
      associated with MCPC risk (nonsignificant). However, no association was observed
      in ever smokers (pheterogeneity = 0.03). Hazard ratios were consistent across
      strata of other potential effect modifiers. Considering MD scores excluding
      alcohol, mMED-containing models generally fitted better than aMED-containing
      models, particularly in men. Although associations somewhat differed when all
      pancreatic cancers were considered instead of MCPC, the overall conclusion was
      similar. In conclusion, MD adherence was not associated with pancreatic cancer
      risk in a pooled analysis of two Dutch cohorts.

PMID- 30230537
TI  - Inhibition of MYC attenuates tumor cell self-renewal and promotes senescence in
      SMARCB1 deficient Group 2 Atypical Teratoid Rhabdoid Tumors to suppress tumor
      growth in vivo.
AB  - Loss of SMARCB1 is the hallmark genetic event that characterizes rhabdoid tumors
      in children. Rhabdoid tumors of the brain (ATRT) occur in young children and are
      particularly challenging with poor long term survival. SMARCB1 is a member of the
      SWI/SNF chromatin remodeling complex that is responsible for determining cellular
      pluripotency and lineage commitment. The mechanisms by which SMARCB1 deletion
      results in tumorigenesis remain unclear. Recent studies demonstrate that ATRT
      consists of 3 genomic sub-groups with a subset of poor outcome tumors expressing
      high BMP and MYC pathway activation. Here we show that MYC occupies distinct
      promoter loci in ATRT compared to embryonic stem (ES) cells. Further, using human
      ATRT cell lines, patient-derived cell culture, ex-vivo patient-derived tumor, and
      orthotopic xenograft models, we show that MYC inhibition is a molecular
      vulnerability in SMARCB1-deleted tumors and that such inhibition effectively
      suppresses BMP and pluripotency-associated genomic programs, attenuates tumor
      cell self-renewal, promotes senescence and inhibits ATRT tumor growth in vivo.
      Transgenic expression of Omomyc (a bona-fide MYC dominant negative) or chemical
      inhibition of MYC transcriptomic programs with the BET inhibitor JQ1 phenocopy
      genetic depletion of MYC, effectively restricting ATRT tumor growth and opening a
      promising therapeutic avenue for rhabdoid tumors in children. This article is
      protected by copyright. All rights reserved.

PMID- 30230538
TI  - A comparison of group contingencies on academic compliance.
AB  - We used a reversal design with an embedded multielement design to compare the
      effects of an independent group contingency and a randomized dependent group
      contingency on compliance with assigned literacy worksheets in a first-grade
      general education classroom. Nine participants were selected based on low levels
      of compliance in baseline or by teacher identification. Results indicated that
      both group contingencies increased compliance relative to baseline for the
      majority of participants. The independent condition produced higher levels of
      compliance for four students and the randomized dependent condition produced
      higher levels of compliance for one student. For four students, the two group
      contingencies were equally effective. A preference assessment indicated that the
      majority of target students preferred the randomized dependent condition and the
      majority of nontarget students preferred the independent condition. A number of
      potential explanations for our preference findings, including the possible role
      of obtained reinforcement, are discussed.

PMID- 30230539
TI  - Circulating sCD27 and sCD30 in pre-diagnostic samples collected fifteen years
      apart and future non-Hodgkin lymphoma risk.
AB  - Elevated serum sCD27 and sCD30 from a single banked sample have been associated
      with future non-Hodgkin lymphoma risk; however, the etiologic relevance of this
      finding is unclear. To address this question, we conducted a case-control study
      (235 cases, 235 controls) nested within the CLUE-I and CLUE-II cohorts, which
      enrolled participants in 1974 and 1989 respectively in Washington County,
      Maryland. Our study features a subset of 102 cases and 102 controls with two
      banked pre-diagnostic samples each, collected fifteen years apart. In analyses
      involving an individual sample per subject, both sCD27 and sCD30 were associated
      with NHL diagnosed up to 20 years later. In analyses involving repeated samples,
      cases were significantly more likely than controls to have higher analyte levels
      in the CLUE-II vs. CLUE-I sample for sCD27 (P = 0.006) but not sCD30 (P = 0.16).
      In joint analyses of dichotomized analyte levels in both samples, the strongest
      NHL association observed for sCD27 was for having below-median levels in CLUE-I
      and above-median levels in CLUE-II [odds ratio (OR) 3.6, 95% confidence interval
      (CI) 1.4-9.2 vs. below-median levels in both). In joint analyses for sCD30, the
      strongest NHL association was observed for having above-median levels in both
      samples (OR 1.7, 95% CI 0.8-3.7), particularly for cases diagnosed >10 years
      after the CLUE-II sample (OR 2.4, 95% CI 0.9-6.7). Our findings suggest that
      sCD27 is a disease marker for NHL and add to the weight of evidence that elevated
      circulating sCD30 is a marker of increased NHL susceptibility. This article is
      protected by copyright. All rights reserved.

PMID- 30230540
TI  - MiR-499 regulates myoblast proliferation and differentiation by targeting
      transforming growth factor beta receptor 1.
AB  - MicroRNAs (miRNAs or miRs) are small noncoding RNAs that play critical roles in
      muscle cell proliferation and differentiation via post-transcriptional regulation
      of gene expression. Here, based on our previous high-throughput sequencing
      results, we evaluated miRNA-499 (miR-499) functions during myoblast proliferation
      and differentiation. In addition, we analyzed miR-499 expression profiles and
      characterized the associated functional roles. MiR-499 is known to be a skeletal
      muscle fiber-type-associated miRNA. However, its roles in skeletal myoblast
      proliferation and differentiation are poorly understood. MiR-499 overexpression
      promoted C2C12 cell proliferation and significantly attenuated C2C12 cell
      myogenic differentiation. Furthermore, miR-499 inhibition enhanced C2C12 cell
      proliferation and suppressed C2C12 cell differentiation. Using dual-luciferase
      reporter assays and western blot analysis, we confirmed that miR-499 targeted
      transforming growth factor beta receptor 1 (TGFbetaR1), a known regulator of
      skeletal myoblast development. Additionally, our RNA interference analysis, in
      which TGFbetaR1 was downregulated, showed that TGFbetaR1 significantly promoted
      the differentiation of C2C12 cells and inhibited their proliferation.

PMID- 30230541
TI  - Frequency and clinical significance of NF1 mutation in lung adenocarcinomas from
      East Asian patients.
AB  - NF1 is a tumor suppressor gene that negatively regulates Ras signaling. NF1
      deficiency plays an important role in carcinogenesis. To investigate the
      frequency and clinical significance of NF1 mutation, we examined mutation status
      of NF1, TP53, LKB1 and RB1 in 704 surgically resected lung adenocarcinomas from
      East Asian patients using semiconductor-based Ion Torrent sequencing platform.
      Common driver events, including mutations in EGFR, KRAS, HER2, BRAF, MET, and
      fusions affecting ALK, RET and ROS1, were also concurrently detected. The
      correlation between NF1 mutations and clinicomolecular features of patients was
      further evaluated. Among 704 patients, 42 NF1 mutations were found in 33 patients
      (33/704, 4.7%), including 14 patients harboring EGFR/NF1 comutations (14/33,
      42.4%). Comparing with EGFR-mutant patients, patients harboring NF1 mutations
      were closely associated with solid component subtype (p = 0.028). Comparing with
      KRAS mutations, NF1 mutations were found more common in female and never smokers
      (p = 0.003 and p = 0.004, respectively). Kaplan-Meier survival analysis revealed
      that patients harboring NF1 mutation had similar disease-free survival (DFS) and
      overall survival (OS) with patients with KRAS mutation. Although frequently
      overlapped with EGFR mutation, patients harboring NF1 mutation had significantly
      shorter DFS (p = 0.019) and OS (p = 0.004) than patients with EGFR mutation.
      During follow-up, one female patient with EGFR exon 19 deletion and NF1 Q1815X
      comutation showed poor response to EGFR TKIs (Gefitinib and Osimertinib) after
      disease relapse. In conclusion, NF1 mutations define a unique molecular and
      clinicopathologic subtype of lung adenocarcinoma. Examination of NF1 mutation may
      contribute to molecular subtyping and therapeutic intervention of lung
      adenocarcinoma.

PMID- 30230542
TI  - HPV16 E6 promotes cervical cancer cell migration and invasion by downregulation
      of NHERF1.
AB  - HPV16 is the predominant type of HPV causing invasive cervical cancer. However,
      the underlying molecular mechanism of the unparalleled carcinogenic power of
      HPV16 compared with other types of High-risk (HR)-HPV including HPV18 is still
      elusive. The PDZ binding motif (PBM) of high-risk HPV E6 plays an important role
      in neoplasia and progression of cervical cancer. HPV16 E6 rather than HPV18 E6,
      interacted with NHERF1 by its PBM region, and induced degradation of NHERF1.
      NHERF1 retarded the assembly of cytoskeleton by downregulation of ACTN4, thereby
      inhibited the migration and invasion of cervical cancer cells in both cell and
      mouse model. HPV16 E6 was confirmed to enhance actin polymerization with
      increased ACTN4 level by downregulation of NHERF1, and result in enhanced
      migration and invasion of cervical cancer cells. GSEA analysis of cervical cancer
      specimens also showed that HPV16 E6 rather than HPV18 E6, was significantly
      associated with actin cytoskeleton assembly. That downregulation of NHERF1 by
      HPV16 E6 promoted cytoskeleton assembly and cell invasion, was an important cause
      in cervical cancer carcinogenesis. These findings provided the differential
      mechanism between HPV16 E6 and HPV18 E6 in the development and progression of
      cervical cancer, which may partially explain the differences of carcinogenic
      power between these two types of HR-HPVs. This article is protected by copyright.
      All rights reserved.

PMID- 30230543
TI  - Efficient penetration of Scp01-b and its DNA transfer abilities into cells.
AB  - The in vivo application potential of viral-based gene delivery approaches is
      hindered by a risk of insertional oncogenesis. Of the many delivery methods, cell
      penetrating peptides (CPP)-based delivery has good biocompatibility and
      biodegradability. However, low efficiency is still the disadvantage of CPPs-based
      nucleic acid transfection, and delivery efficiency may vary from different CPPs.
      Here, we describe Scp01-b, as a new CPP, which can enter cultured cell lines and
      primary cultured cells examined by fluorescence microscopy and quantitative
      assay, the internalization process is a concentration, temperature, and
      incubation time-dependent manner. Scp01-b does not insert into the membrane
      directly and its uptake is mediated through endocytosis pathway. Moreover, Scp01
      b could mediate the uptake of plasmid DNA into the Caski and HSC-T6 cells, and we
      noted that Scp01-b-mediated transfection efficiency was nearly the same with
      traditional liposome (TurboFectin)-mediated transfection. These findings suggest
      that Scp01-b can act as a useful tool for non-viral-based delivery in further
      application such as reprogramming and gene editing.

PMID- 30230544
TI  - Chloride channel-3 mediates multidrug resistance of cancer by upregulating P
      glycoprotein expression.
AB  - Chloride channel-3 (ClC-3), a member of the ClC family of voltage-gated Cl-
      channels, is involved in the resistance of tumor cells to chemotherapeutic drugs.
      Here, we report a new mechanism for ClC-3 in mediating multidrug resistance
      (MDR). ClC-3 was highly expressed in the P-glycoprotein (P-gp)-dependent human
      lung adenocarcinoma cell line (A549)/paclitaxel (PTX) and the human breast
      carcinoma cell line (MCF-7)/doxorubicin (DOX) resistant cells. Changes in the ClC
      3 expression resulted in the development of drug resistance in formerly drug
      sensitive A549 or MCF-7 cells, and drug sensitivity in formerly drug-resistant
      A549/Taxol and MCF-7/DOX cells. Double transgenic MMTV-PyMT/CLCN3 mice with
      spontaneous mammary cancer and ClC-3 overexpression demonstrated drug resistance
      to PTX and DOX. ClC-3 expression upregulated the expression of MDR1 messenger RNA
      and P-gp by activating the nuclear factor-kappaB (NF-kappaB)-signaling pathway.
      These data suggest that ClC-3 expression in cancer cells induces MDR by
      upregulating NF-kappaB-signaling-dependent P-gp expression involving another new
      mechanism for ClC-3 in the development of drug resistance of cancers.

PMID- 30230545
TI  - Slug mediates myofibroblastic differentiation to promote fibrogenesis in buccal
      mucosa.
AB  - Epithelial-mesenchymal transition (EMT) has been implicated in fibrogenesis and
      carcinogenesis; however, the exact role of EMT-inducer Slug in the progression of
      precancerous oral submucous fibrosis (OSF) has not been investigated. In the
      current study, we showed that the expression of Slug was upregulated in OSF
      tissues and associated with various myofibroblast markers. After silence of Slug
      in fibrotic buccal mucosal fibroblasts (fBMFs), the elevated myofibroblast
      activities and fibrosis markers were all downregulated. Our data revealed that
      arecoline, an areca nut alkaloid, increased the expression of Slug in normal
      BMFs, and inhibition of Slug successfully prevented the arecoline-induced
      myofibroblast activation. Additionally, overexpression of Slug in BMFs stimulated
      the activities of myofibroblasts, indicating that upregulation of Slug by
      arecoline contributes to the myofibroblast transdifferentiation. Most
      importantly, Slug was able to bind to the E-box of type I collagen, leading to
      increased expression of type I collagen. Altogether, this study demonstrated the
      abnormal elevation of Slug in OSF and its significance in arecoline-induced
      fibrogenesis. Moreover, downregulation of Slug could be a potential target for
      OSF remedy via suppression of myofibroblast activities and type I collagen.

PMID- 30230547
TI  - Oxidative protein folding: state-of-the-art and current avenues of research in
      plants.
AB  - Contents Summary I. Introduction II. Formation and isomerization of disulfides in
      the ER and the Golgi apparatus III. The disulfide relay in the mitochondrial
      intermembrane space: why are plants different? IV. Disulfide bond formation on
      luminal proteins in thylakoids V. Conclusion Acknowledgements References SUMMARY:
      Disulfide bonds are post-translational modifications crucial for the structure
      and function of thousands of proteins. Their formation and isomerization,
      referred to as oxidative folding, require specific protein machineries found in
      oxidizing subcellular compartments, namely the endoplasmic reticulum and the
      associated endomembrane system, the intermembrane space of mitochondria and the
      thylakoid lumen of chloroplasts. At least one protein component is required for
      transferring electrons from substrate proteins to an acceptor that is usually
      molecular oxygen. For oxidation reactions, incoming reduced substrates are
      oxidized by thiol-oxidoreductase proteins (or domains in case of chimeric
      proteins), which are usually themselves oxidized by a single thiol oxidase, the
      enzyme generating disulfide bonds de novo. By contrast, the description of the
      molecular actors and pathways involved in proofreading and isomerization of
      misfolded proteins, which require a tightly controlled redox balance, lags
      behind. Herein we provide a general overview of the knowledge acquired on the
      systems responsible for oxidative protein folding in photosynthetic organisms,
      highlighting their particularities compared to other eukaryotes. Current research
      challenges are discussed including the importance and specificity of these
      oxidation systems in the context of the existence of reducing systems in the same
      compartments.

PMID- 30230546
TI  - Spontaneous retroperitoneal liposarcoma in a free-ranging juvenile golden-headed
      lion tamarin (Leontopithecus chrysomelas).
AB  - Malignant adipocytic neoplasia is rare among nonhuman primates. We report the
      gross and microscopic features of a retroperitoneal liposarcoma with
      myxofibrosarcoma-like dedifferentiation in a free-ranging juvenile golden-headed
      lion tamarin (Leontopithecus chrysomelas). To our knowledge, this is the first
      report of such tumor subtype in New World primates.

PMID- 30230548
TI  - Transmission detectors are safe and the future for patient-specific QA in
      radiation therapy.

PMID- 30230549
TI  - BES1 hinders ABSCISIC ACID INSENSITIVE5 and promotes seed germination in
      Arabidopsis.
AB  - Proper regulation of seed germination is essential for the successful propagation
      of a plant. The transcription factor ABSCISIC ACID INSENSITIVE5 (ABI5) of the
      abscisic acid (ABA) signaling pathway plays a central role in the inhibition of
      seed germination. ABI5 is precisely regulated by the core ABA signaling
      components and multiple other factors. However, the complex regulatory network of
      ABI5 remains largely unknown. In this study, we determined the biochemical
      interaction between ABI5 and the BRINSENSITIVE1 (BRI1)-EMS-SUPPRESSOR1 (BES1)
      transcription factor of the brassinosteroid (BR) signaling pathway, as well as
      the function of BES1 regulating ABI5 during seed germination in Arabidopsis. BES1
      directly interacts with ABI5 both in vitro and in vivo. The bZIP domain of ABI5,
      which is responsible for DNA binding, is critical for ABI5 binding to BES1. The
      interaction of BES1 with ABI5 significantly suppressed the binding of ABI5 to the
      promoter regions of downstream genes, which resulted in their reduced expression
      and consequently facilitated seed germination. This study shed new light on the
      coordination of multiple signaling pathways during seed germination. In
      particular, BES1 directly binds to ABI5, which interferes with its
      transcriptional activity and suppresses ABA signaling output.

PMID- 30230550
TI  - Lay conceptions of norm-based approach and avoidance motivation: Implications for
      the performance-approach and performance-avoidance goal relation.
AB  - OBJECTIVE: Performance-approach goals and performance-avoidance goals are
      conceptually distinct, but they are often moderately or even highly positively
      correlated. The present research examines lay conceptions of approach and
      avoidance motivation as a moderator of this intergoal relation. METHOD: Study 1
      (N = 281) assessed whether participants considered norm-based approach motivation
      as being the same or different from norm-based avoidance motivation and tested
      these conceptions as a moderator of the performance goal correlation. Study 2 (N
      = 990) measured and experimentally manipulated lay conceptions. RESULTS: In both
      studies, individuals who viewed approach and avoidance motivation as different
      exhibited a smaller performance goal correlation and lower performance-based goal
      adoption than those who viewed approach and avoidance goals as the same. Findings
      from experimentally manipulated conceptions provided further clarity regarding
      the precise nature of the relations and mean differences observed. Specifically,
      moderation was driven by the different condition (where the differences between
      approach and avoidance were highlighted). CONCLUSIONS: This research sheds light
      on the nature and magnitude of the focal performance-based goal correlation and
      highlights the value of attending to lay conceptions of approach and avoidance
      motivation as well as lay conceptions of ability.

PMID- 30230551
TI  - A system for the real-time tracking of operant behavior as an application of 3D
      camera.
AB  - The capacity of 3D cameras to measure many different aspects of behavior (e.g.,
      velocity, pattern, and posture) could contribute to the understanding of
      behavior. The present article describes a system for the real-time tracking of
      operant behavior, which is applicable to other domains of behavioral science as
      well. Methods for real-time 3D tracking of animal behavior are described, along
      with sample C++ programs. A demonstration using one zebrafish as a subject
      indicated that the present system successfully tracked the 3D motion of the fish.
      Moreover, the acquisition of a target response (i.e., approach to a corner of the
      aquarium) was demonstrated with the arrangement of a reinforcement contingency at
      the corner in the absence of a traditional, salient operandum. The system offers
      the capacity to characterize more completely ongoing behavior in learning tasks
      across a range of species than simply performance of discrete operant responses.
      The system also is capable of tracking multiple individuals simultaneously so it
      is possible both to study social interactions and arrange contingencies for
      engaging in social behavior. Other possible applications of 3D cameras are
      discussed.

PMID- 30230552
TI  - Anti-D from alloimmunization versus RhIG: detective work in the blood bank and
      transfusion medicine services.
AB  - BACKGROUND: The blood bank and transfusion medicine services (BBTMS) engages with
      electronic health records (EHRs), clinicians, and outside hospitals (OHs) to
      obtain comprehensive patient history to optimize care. Detection of anti-D in a
      pregnant patient underscores this work. Differentiating passive anti-D due to
      RhIG administration versus alloanti-D affects clinical decision making. The
      objectives of this study were to identify the required steps, barriers, and
      outcomes of anti-D investigations in obstetric patients. STUDY DESIGN AND
      METHODS: This retrospective case series reviewed nine pregnant patients over 24
      months, for whom anti-D was identified with no reported RhIG history. Six steps
      were performed to ascertain anti-D history: 1) review the on-site EHR; 2) contact
      the on-site obstetrician, 3) review history from the automatic health information
      exchange (HIE) with OHs using the same EHR platform, 4) request information from
      OHs with a shared EHR platform and without automatic HIE, 5) contact the OH
      BBTMS, and 6) communicate with the outside ambulatory practice (OAP). RESULTS:
      The investigations revealed that eight of nine patients received RhIG before
      their presentation. Five patients received RhIG at an OH's emergency department
      and three at an OAP. One patient's history remained unknown after initial
      investigations; however, a subsequent sample unveiled a confounding alloantibody.
      CONCLUSION: In the absence of a national HIE, continuity of care suffers through
      omission of critical information. Strategies to avoid confusing passive anti-D
      and alloanti-D include expanding HIE capabilities and use of patient
      identification cards with critical BBTMS information to include RhIG
      administration dates.

PMID- 30230553
TI  - Determination of baseline values for routine ophthalmic tests in bearded capuchin
      (Sapajus libidinosus).
AB  - BACKGROUND: Establish baseline values for ophthalmic diagnostic tests in Sapajus
      libidinosus. METHODS: Ophthalmic diagnostic tests, namely Schirmer tear test 1
      (STT-1), intraocular pressure (IOP), B-mode ultrasound, culture of the bacterial
      conjunctival microbiota, and conjunctival exfoliative cytology, were performed in
      15 S. libidinosus. RESULTS: Mean values found were as follows: 2.50 +/- 2.94
      mm/min for the STT-1; 13.3 +/- 3.32 mm Hg for the IOP; 2.47 +/- 0.41 mm for the
      depth of the anterior chamber; 2.86 +/- 0.96 mm for the axial length of the lens;
      10.97 +/- 0.48 mm for the depth of the vitreous chamber; and 16.32 +/- 1.24 mm
      for the axial length of the eyeball. The bacterial genus most frequently found
      was Staphylococcus spp. Conjunctival cytology showed intermediate epithelial,
      squamous superficial epithelial, and keratinized cells. CONCLUSIONS:
      Determination of baseline values for eye measurements and ophthalmic tests will
      assist in the diagnosis of eye diseases in S. libidinosus monkeys.

PMID- 30230554
TI  - Pathways to resilience: adapting to sea level rise in Los Angeles.
AB  - Los Angeles (LA) County's coastal areas are highly valued for their natural
      benefits and their economic contributions to the region. While LA County already
      has a high level of exposure to flooding (e.g. people, ports, and harbors),
      climate change and sea level rise will increase flood risk; anticipating this
      risk requires adaptation planning to mitigate social, economic, and physical
      damage. This study provides an overview of the potential effects of sea level
      rise on coastal LA County and describes adaptation pathways and estimates
      associated costs in order to cope with sea level rise. An adaptation pathway in
      this study is defined as the collection of measures (e.g., beach nourishment,
      dune restoration, flood-proofing buildings, and levees) required to lower flood
      risk. The aim of using different adaptation pathways is to enable a transition
      from one methodology to another over time. These pathways address uncertainty in
      future projections, allowing for flexibility among policies and potentially
      spreading the costs over time. Maintaining beaches, dunes, and their natural
      dynamics is the foundation of each of the three adaptation pathways, which
      address the importance of beaches for recreation, environmental value, and flood
      protection. In some scenarios, owing to high projections of sea level rise,
      additional technical engineering options such as levees and sluices may be needed
      to reduce flood risk. The research suggests three adaptation pathways,
      anticipating a +1 ft (0.3 m) to +7 ft (+2 m) sea level rise by year 2100. Total
      adaptation costs vary between $4.3 and $6.4 bn, depending on measures included in
      the adaptation pathway.

PMID- 30230555
TI  - Dispersal biophysics and adaptive significance of dimorphic diaspores in the
      annual Aethionema arabicum (Brassicaceae).
AB  - Heteromorphic diaspores (fruits and seeds) are an adaptive bet-hedging strategy
      to cope with spatiotemporally variable environments, particularly fluctuations in
      favourable temperatures and unpredictable precipitation regimes in arid climates.
      We conducted comparative analyses of the biophysical and ecophysiological
      properties of the two distinct diaspores (mucilaginous seed (M+ ) vs indehiscent
      (IND) fruit) in the dimorphic annual Aethionema arabicum (Brassicaceae), linking
      fruit biomechanics, dispersal aerodynamics, pericarp-imposed dormancy, diaspore
      abscisic acid (ABA) concentration, and phenotypic plasticity of dimorphic
      diaspore production to its natural habitat and climate. Two very contrasting
      dispersal mechanisms of the A. arabicum dimorphic diaspores were revealed.
      Dehiscence of large fruits leads to the release of M+ seed diaspores, which
      adhere to substrata via seed coat mucilage, thereby preventing dispersal
      (antitelechory). IND fruit diaspores (containing nonmucilaginous seeds) disperse
      by wind or water currents, promoting dispersal (telechory) over a longer range.
      The pericarp properties confer enhanced dispersal ability and degree of dormancy
      on the IND fruit morph to support telechory, while the M+ seed morph supports
      antitelechory. Combined with the phenotypic plasticity to produce more IND fruit
      diaspores in colder temperatures, this constitutes a bet-hedging survival
      strategy to magnify the prevalence in response to selection pressures acting over
      hilly terrain.

PMID- 30230556
TI  - Identification of optimal mother wavelets in survival prediction of lung cancer
      patients using wavelet decomposition-based radiomic features.
AB  - PURPOSE: To identify the optimal mother wavelets in survival prediction of lung
      cancer patients using wavelet decomposition-based (WDB) radiomic features in CT
      images. MATERIALS AND METHODS: The CT images of patients with histologically
      confirmed nonsmall cell lung carcinomas (NSCLCs) in training (Dataset T; n = 162)
      and validation (Dataset V; n = 143) datasets were analyzed for this study. The
      optimal mother wavelets were identified based on the impacts of the WDB radiomic
      features on the patient survival times. Four hundred and thirty-two three
      dimensional WDB radiomic features were calculated from regions of interest (ROI)
      of 162 tumor contours. A Coxnet algorithm was used to select a subset of radiomic
      features (signature) based on the prediction of survival times with a fivefold
      cross validation. The impacts of the radiomic features on the patients' survival
      times were assessed by using a multivariate Cox proportional hazard regression
      (MCPHR) model. The major contribution of this study was to identify optimal
      mother wavelets based on a maximization of a novel ranking index (RI)
      incorporating the Coxnet cross-validated partial log-likelihood and the summation
      of the P-values of the radiomic features in the MCPHR model on Dataset T. The
      prognostic performance of the optimal mother wavelets was validated based on the
      concordance index (CI) of the MCPHR models when applied to Dataset V. The
      proposed approach was tested by using 31 mother wavelets from 6 wavelet families
      that were available in a commercially available software (Matlab(r) 2016b).
      RESULTS: The optimal mother wavelets were Symlet 5 and Biorthogonal 2.6 at 128
      requantization levels, which yielded RIs of 4.27 +/- 0.29 (3 features) and 6.50
      +/- 0.50 (5 features), respectively. The CIs of the MCPHR models of Symlet 5 were
      0.66 +/- 0.03 (Dataset T) and 0.64 +/- 0.00 (Dataset V), whereas those of
      Biorthogonal 2.6 were 0.68 +/- 0.03 (Dataset T) and 0.62 +/- 0.02 (Dataset V).
      The radiomic signatures included the GLRLM-based LHL gray level nonuniformity
      feature that demonstrated statistically significant differences in stratifying
      patients with better and worse prognoses in Datasets T and V. CONCLUSION: This
      study has revealed the potential of Symlet and Biorthogonal mother wavelets in 
      the survival prediction of lung cancer patients by using WDB radiomic features in
      CT images.

PMID- 30230558
TI  - Effects of Strength Training in Amyotrophic Lateral Sclerosis: How Much Do We
      Know?

PMID- 30230557
TI  - Action-associated modulation of visual event-related potentials evoked by
      abstract and ecological stimuli.
AB  - This study investigated the influence of action-associated predictive processes
      on visual ERPs. In two experiments, we sought evidence for sensory attenuation
      (SA) indexed by ERP amplitude reductions for self-induced stimuli when compared
      to passive viewing of the same images. We assessed if SA is (a) present for both
      ecological and abstract stimuli (pictures depicting hands or checkerboards), (b)
      modulated by the degree of stimulus predictability (certain or uncertain action
      effect contingencies), and (c) sensitive to laterality of hand movements
      (dominant or subdominant hand actions). We found reduced occipital responses in
      the early 77-90 ms time interval (C1 component), irrespective of stimulus type,
      predictability, or the laterality of hand movements. However, the subsequent P1
      component was increased (rather than reduced) for all action-associated stimuli.
      In addition, this P1 effect was influenced by the degree of stimulus
      predictability for ecological stimuli only. Finally, the posterior N1 component
      was not modulated by self-initiated actions. Overall, our findings indicate that
      movement-related predictive processes attenuate early visual responses. Moreover,
      we propose that amplitude modulations in the P1 time range reflect the
      interaction between expectation-based SA and attention-associated amplitude
      enhancements. These results can have implications for assessing the influence of
      action-associated predictions on visual processing in psychiatric disorders
      characterized by aberrant sensory predictions and alterations in hemispheric
      asymmetry, such as schizophrenia.

PMID- 30230559
TI  - Anatomy of the vestibulum esophagi and surgical implications during prosthetic
      laryngoplasty in horses.
AB  - OBJECTIVE: To describe the anatomy of the entry to the equine esophagus
      (vestibulum esophagi) and to assess the risk of penetrating its adventitia and/or
      lumen during laryngoplasty. STUDY DESIGN: Ex vivo cadaveric study. SAMPLE
      POPULATION: Five isolated equine larynges and 39 equine head and neck specimens.
      METHODS: The anatomy of the vestibulum esophagi was studied by dissection of 5
      cadaver specimens. Then, a bilateral laryngoplasty was performed, including 5
      suture placements through the muscular processes, caudal, rostral, and sagittal,
      with straight and curved needles. Two of the 3 surgeons performing the
      implantations were unaware of the goals of the study. Suture positions and
      iatrogenic trauma to the lumen and/or adventitia of the vestibulum esophagi were
      identified during dissection of the specimens. Risk factors for penetrating the
      adventitia were evaluated with a multivariate regression model. RESULTS: The
      vestibulum esophagi spans between both wings of the thyroid cartilage over the
      entire width of the larynx, covering the rostral spine (arcuate crest) of the
      arytenoid cartilages. It is covered by the thyropharyngeus and cricopharyngeus
      muscles. Masked surgeons were associated with a significantly higher number of
      adventitia penetrations (72%) compared to the nonmasked surgeon (9%). The lumen
      of the vestibulum esophagi was penetrated in 4.6% of suture placements and only
      by the 2 masked surgeons. CONCLUSION: Penetration of the adventitia was more
      common when surgeons were unaware of the anatomical extent of the vestibulum
      esophagi. CLINICAL SIGNIFICANCE: Anatomical knowledge of the extent of the
      vestibulum esophagi reduces the risk of penetrating its lumen or adventitia
      during suture placement on the muscular process of the arytenoid cartilage.

PMID- 30230560
TI  - Muscle does not drive persistent posttraumatic elbow contracture in a rat model.
AB  - INTRODUCTION: Posttraumatic elbow contracture is clinically challenging because
      injury often disrupts multiple periarticular soft tissues. Tissue specific
      contribution to contracture, particularly muscle, remains poorly understood.
      METHODS: In this study we used a previously developed animal model of elbow
      contracture. After surgically inducing a unilateral soft tissue injury, injured
      limbs were immobilized for 3, 7, 21, and 42 days (IM) or for 42 IM with 42 days
      of free mobilization (42/42 IM-FM). Biceps brachii active/passive mechanics and
      morphology were evaluated at 42 IM and 42/42 IM-FM, whereas biceps brachii and
      brachialis gene expression was evaluated at all time points. RESULTS: Injured
      limb muscle exhibited significantly altered active/passive mechanics and
      decreased fiber area at 42 IM but returned to control levels by 42/42 IM-FM. Gene
      expression suggested muscle growth rather than a fibrotic response at 42/42 IM
      FM. DISCUSSION: Muscle is a transient contributor to motion loss in our rat model
      of posttraumatic elbow contracture. Muscle Nerve, 2018.

PMID- 30230561
TI  - Functional exercise capacity evaluated by timed walk tests in myasthenia gravis.
AB  - INTRODUCTION: We sought to evaluate the test-retest reliability and construct
      validity of the 6- and 2-minute walk tests (6mWT and 2mWT, respectively) in
      patients with myasthenia gravis (MG). METHODS: Thirty-one patients with
      generalized MG were enrolled in this study. The 6mWT, 2mWT, MG-specific quality
      of life questionnaire Turkish version (MG-QoL15T), quantitative myasthenia gravis
      test (QMG), and pulmonary function tests were administered. RESULTS: The
      intraclass correlation coefficients of 2mWT and 6mWT were 0.894 and 0.932,
      respectively. The 6mWT and 2mWT had moderate correlations with forced vital
      capacity, maximal inspiratory pressure, QMG score, and MG-QoL15T score (rho for
      6mWT: 0.579, 0.539, -0.572, and -0.474; rho for 2mWT: 0.460, 0.446, -0.532, 
      0.457). Both tests had similar performances for predicting disease severity (area
      under the curve = 0.761 for 6mWT and 0.759 for 2mWT). DISCUSSION: The 6mWT and
      2mWT have excellent test-retest reliability as well as moderate construct
      validity for the evaluation of functional exercise capacity patients with MG.
      Muscle Nerve, 2018.

PMID- 30230562
TI  - A New Template and Teleoperation System for Human-Guided Spine Surgery.
AB  - Fluoroscopy-guided placement of pedicle screws is usually used to position
      pedicle screws, although it is highly risky due to lack of accuracy during
      operation and surgeon's intensive labor requirement during surgery. In this
      study, a new method was introduced to consider the issues and we tried to reduce
      the risk of pedicle screw placement and drilling process. To put pedicle screws
      in the correct position and orientation, a specific drill guide is designed and
      fabricated by additive manufacturing technology. In addition, since the drilling
      process is remarkably important and it is usually dependent on surgeon skill,
      therefore a teleoperation system is proposed to perform this task. In order to
      let the surgeon to have better control on the patient, a control scheme including
      position and velocity signals along with surgeon force and reaction force of
      vertebra was proposed. This helped the surgeon for proper control on the patient
      during surgery. A force estimation algorithm was presented to eliminate measuring
      external force signal. Consequently, 10 vertebras were used to evaluate specific
      drill guide and teleoperation system simultaneously. Then, the computed
      tomography evaluation demonstrated that Kirschner wire trajectories followed the
      planned axes with an error between 1 and 2 mm in 20% of cases and less than 1 mm
      in 80% of cases. The results obtained by the teleoperation system showed that the
      surgeon, in the master side, has proper control over the patient body in the
      slave side because the slave robot followed the master position. Furthermore, the
      surgeon in the master side sensed the reaction force of vertebra in the slave
      side appropriately.

PMID- 30230563
TI  - Persistent abdominal pain related to portal vein thrombosis in young adult with
      sickle cell disease.

PMID- 30230564
TI  - A systematic review of the use of music interventions to improve outcomes for
      patients undergoing hip or knee surgery.
AB  - AIM: To examine the effectiveness of music as an adjunct treatment for pain,
      anxiety, and/or postoperative delirium, for patients undergoing hip or knee
      surgery. BACKGROUND: Patients undergoing hip or knee surgery are known to
      experience pain and anxiety before and after surgery and be prone to
      postoperative delirium. DESIGN: Quantitative systematic review. DATA SOURCES:
      CENTRAL, Embase, Ovid MEDLINE, CINAHL, and PsycINFO databases were systematically
      searched without time limits (to June 2018). REVIEW METHODS: A systematic search
      yielded 10 randomized controlled trials and quasi-experimental designs. Studies
      were appraised using the Cochrane Risk of Bias Tool. Data were extracted using
      the Effective Practice and Organization of Care data extraction tool. RESULTS:
      Mixed results were found for the effect of music on anxiety, pain, and
      postoperative delirium in patients undergoing hip or knee surgery. Six of 10
      included studies provided evidence that music can improve anxiety, pain, or
      postoperative delirium outcomes for patients undergoing hip or knee surgery.
      Music effectively reduced anxiety in one of three studies. Three of seven studies
      reported benefits of music for reducing postoperative pain. Positive effects of
      music on postoperative delirium were reported in all three studies that evaluated
      this outcome. Within group improvements were observed in many of the studies.
      CONCLUSION: Music has the potential to improve outcomes of anxiety, pain, and
      postoperative delirium, for patients undergoing hip or knee surgery. The low
      number of studies found indicates results should be treated with caution. Further
      studies are required to provide strong evidence generalizable to a broader
      population.

PMID- 30230565
TI  - Sirtuin 6 inhibits myofibroblast differentiation via inactivating transforming
      growth factor-beta1/Smad2 and nuclear factor-kappaB signaling pathways in human
      fetal lung fibroblasts.
AB  - Fibroblast-to-myofibroblast differentiation, which is characterized by increased
      expression of alpha-smooth muscle actin, is known to be involved in the
      pathogenesis of idiopathic pulmonary fibrosis. Sirtuin 6 (SIRT6), a member of the
      sirtuin family, has been proved to inhibit epithelial-to-mesenchymal transition
      during idiopathic pulmonary fibrosis. However, the function of SIRT6 in lung
      myofibroblast differentiation is still obscure. Transforming growth factor-beta1
      (TGF-beta1) is one of the main factors that can powerfully promote myofibroblast
      differentiation. In the current study, we aimed to explore the role of SIRT6 in
      the cellular model of fibroblast-to-myofibroblast differentiation induced by TGF
      beta1 using human fetal lung fibroblasts (HFL1). We demonstrated that the SIRT6
      protein level is upregulated by TGF-beta1 in HFL1 cells. Overexpression of SIRT6
      significantly suppresses TGF-beta1-induced myofibroblast differentiation in HFL1
      cells. Mechanistically, SIRT6 decreases phosphorylation and nuclear translocation
      of Smad2 under TGF-beta1 stimulation. Nevertheless, mutant SIRT6 (H133Y) without
      histone deacetylase activity fails to inhibit phosphorylation and nuclear
      translocation of Smad2. Meanwhile, SIRT6 interacts with the nuclear factor-kappaB
      (NF-kappaB) subunit p65 and represses TGF-beta1-induced NF-kappaB-dependent
      transcriptional activity, which is also dependent on its deacetylase activity.
      Overexpression of wild-type SIRT6 but not the H133Y mutant inhibits the
      expression of NF-kappaB-dependent genes including interleukin (IL)-1beta, IL-6
      and matrix metalloproteinase-9 (MMP-9) induced by TGF-beta1, all of which have
      been demonstrated to promote myofibroblast differentiation. Collectively, our
      study reveals that SIRT6 prevents TGF-beta1-induced lung myofibroblast
      differentiation through inhibiting TGF-beta1/Smad2 and NF-kappaB signaling
      pathways.

PMID- 30230566
TI  - The remarkable phenotypic variability of the p.Arg269HiS variant in the TRPV4
      gene.
AB  - INTRODUCTION: Mutations in the TRPV4 gene are associated with neuromuscular
      disorders and skeletal dysplasias, which present a phenotypic overlap. METHODS:
      Next-generation sequencing and Sanger sequencing were used to analyze the TRPV4
      gene. RESULTS: We present 2 Polish families with TRPV4-related disorder harboring
      the same p.Arg269His mutation. The disease phenotypic expression was extremely
      variable (from mild scapular winging to severe hypotonia, global weakness,
      inability to walk unaided, congenital contractures, scoliosis, and respiratory
      insufficiency), but did not suggest anticipation. The 2 most severely affected
      patients showed congenital distal contractures of the upper limbs and involvement
      of cranial nerves (manifesting as facial asymmetry and strabismus). The disease
      course seemed to be stable, although in later stages it caused respiratory
      insufficiency and progression of physical disability. DISCUSSION: The phenotypic
      variability observed in p.Arg269His carriers suggests that an additional modifier
      or a more complex pathogenic mechanism exists. Muscle Nerve, 2018.

PMID- 30230567
TI  - Bone scintigraphy analysis of 44 cases of pustulotic arthro-osteitis associated
      with palmoplantar pustulosis.

PMID- 30230568
TI  - Accuracy of Point-of-Care Blood Glucose Level Measurements in Critically Ill
      Patients with Sepsis Receiving High-Dose Intravenous Vitamin C.
AB  - STUDY OBJECTIVE: High-dose intravenous vitamin C is a potential treatment option
      for patients with sepsis and may interfere with point-of-care (POC) blood glucose
      (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis
      affected POC BG level results. DESIGN: Prospective observational pilot study.
      SETTING: Intensive care unit in a large academic tertiary care medical center.
      PATIENTS: Five consecutive critically ill adults hospitalized between April 1 and
      June 1, 2017, who received two or more doses of intravenous vitamin C 1500 mg for
      the treatment of sepsis and had at least two paired POC BG levels and laboratory
      venous BG levels measured within 1 hour of each other during vitamin C therapy.
      MEASUREMENTS AND MAIN RESULTS: The performance of POC BG level measurement was
      compared with the reference method of laboratory BG level measurement. The
      concordance to minimum accuracy criteria for BG meters set forth by the
      International Organization for Standardization (ISO) 15197:2013, the measurement
      of agreement between POC BG level and laboratory BG level using the Bland-Altman
      method, and the clinical accuracy through Parkes error grid analysis were
      assessed. A total of 16 paired POC and laboratory BG level measurements from the
      five patients were included. The accuracy of POC BG with laboratory BG level
      measurements during vitamin C administration according to ISO 15197:2013 criteria
      was 81.3%, which did not meet the minimum accuracy criteria of 95%. The Bland
      Altman analysis showed a mean difference between POC and laboratory BG levels of
      8.9 mg/dl, and the Parkes error grid analysis showed that the differences between
      POC and laboratory BG level measurements would not have resulted in a change in
      clinical action. CONCLUSION: The accuracy and agreement of POC and laboratory BG
      level measurements in critically ill patients receiving vitamin C were consistent
      with previously published reports in critically ill patients not receiving
      vitamin C and did not demonstrate clinically significant interference due to
      vitamin C dosing for sepsis.

PMID- 30230569
TI  - Case of psoriatic erythroderma induced by the discontinuation of the chronic use
      of topical steroid after dialysis initiation and successfully treated with
      secukinumab.

PMID- 30230570
TI  - Severe bupropion XR abuse in a patient with long-standing bulimia nervosa and
      complex PTSD.
AB  - OBJECTIVE: Although abuse of bupropion to achieve euphoria or a stimulant-like
      effect has been described in the literature, to our knowledge abuse of bupropion
      XR to control binge eating and reduce appetite by a patient with eating disorder
      has not been previously reported. METHOD: We report the case of a 22-year-old
      woman with bulimia nervosa and complex PTSD who abused bupropion XR to doses that
      at peak reached 3,000-4,500 mg/day. She suffered from adverse effects including
      headaches, tachycardia, anxiety, insomnia, and, finally, grand mal seizures.
      RESULTS: Unable to control the abuse on her own, she sought inpatient treatment,
      following which she remained off bupropion XR for a year. However, she
      subsequently relapsed. DISCUSSION: The stimulant, euphoriant, and anorexic
      effects of bupropion XR contribute to its potential for abuse, particularly among
      patients with eating disorders. Clinicians are reminded to screen for anorexia
      nervosa and bulimia nervosa histories prior to prescribing this medication, and
      to consider its abuse among eating disorder patients presenting with seizures.
      For patients abusing this medication, motivational interviewing in the context of
      a strong, ongoing therapeutic relationship might help to achieve sustained
      periods of abstinence.

PMID- 30230571
TI  - Omega-3 fatty acids in coronary heart disease: Recent updates and future
      perspectives.
AB  - Incidence of coronary heart disease (CHD) increases worldwide with varying
      etiological factors. In addition to the control of risk factors, dietary
      modification has been recommended to reduce the prevalence. Omega-3 (omega-3)
      fatty acids (FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of
      fish oil are beneficial for the prevention of CHD. The effect can be ascribed to
      anti-inflammatory, vasodilating, antiarrhythmic, antihypertensive activities and
      lowering of triacyl glycerol level. The American Heart Association advises two
      fish meals per week in subjects without CHD or supplementation of 1 g of EPA plus
      DHA per day in subjects with CHD. Despite the beneficial effects of EPA/DHA
      reported in some of the clinical trials, results of many others were inconsistent
      that can be ascribed to short duration of studies, low doses of omega-3 FAs,
      variations in the EPA:DHA ratio, selection of patients with different risk
      factors or interaction of omega-3 FAs with drugs used in the therapy. Therefore,
      well designed clinical trials in various populations are warranted. This article
      discusses the current situation and future prospective of omega-3 FAs in CHD.

PMID- 30230573
TI  - Validation of the clinical perfectionism questionnaire in an eating disorder
      sample: A bifactor approach.
AB  - OBJECTIVE: Clinical perfectionism is involved in the etiology and maintenance of
      eating disorders. Limited research has examined the factor structure of the
      Clinical Perfectionism Questionnaire (CPQ) in clinical eating disorder samples.
      The aim of this research was to examine the validity and reliability of the CPQ
      in a mixed eating disorder sample. METHOD: Patients (N = 211) with an eating
      disorder completed the CPQ at pretreatment. A bifactor model was tested that
      included a general clinical perfectionism factor and two group factors;
      overevaluation of striving and concern over mistakes. The unique contributions
      that general and group factors make to the prediction of eating disorder symptoms
      were also investigated. Unidimensional, correlated two-factor, and bifactor
      models were tested using confirmatory factor analysis. RESULTS: A bifactor
      structure for a revised 10-item version of the CPQ provided the best fit, with a
      strong and reliable general clinical perfectionism factor. The general clinical
      perfectionism factor and the overevaluation of striving group factor explained
      reliable variance in the CPQ, and but only the general factor predicted eating
      disorder symptoms. DISCUSSION: The results suggested that a total score is
      generally appropriate for assessing clinical perfectionism in a clinical eating
      disorder sample.

PMID- 30230572
TI  - Japanese guidelines for the management and treatment of generalized pustular
      psoriasis: The new pathogenesis and treatment of GPP.
AB  - Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent
      fever and systemic flushing accompanied by extensive sterile pustules. The
      committee of the guidelines was founded as a collaborative project between the
      Japanese Dermatological Association and the Study Group for Rare Intractable Skin
      Diseases under the Ministry of Health, Labour, and Welfare Research Project on
      Overcoming Intractable Diseases. The aim of the guidelines was to provide current
      information to aid in the treatment of patients with GPP in Japan. Its contents
      include the diagnostic and severity classification criteria for GPP, its
      pathogenesis, and recommendations for the treatment of GPP. Since there are few
      clinical trial data with high levels of evidence for this rare disease,
      recommendations by the committee are described in the present guidelines.

PMID- 30230574
TI  - Power of the Wilcoxon-Mann-Whitney test for non-inferiority in the presence of
      death-censored observations.
AB  - In clinical trials with patients in a critical state, death may preclude
      measurement of a quantitative endpoint of interest, and even early measurements,
      for example for intention-to-treat analysis, may not be available. For example, a
      non-negligible proportion of patients with acute pulmonary embolism will die
      before 30 day measurements on the efficacy of thrombolysis can be obtained. As
      excluding such patients may introduce bias, alternative analyses, and
      corresponding means for sample size calculation are needed. We specifically
      consider power analysis in a randomized clinical trial setting in which the goal
      is to demonstrate noninferiority of a new treatment as compared to a reference
      treatment. Also, a nonparametric approach may be needed due to the distribution
      of the quantitative endpoint of interest. While some approaches have been
      developed in a composite endpoint setting, our focus is on the continuous
      endpoint affected by death-related censoring, for which no approach for
      noninferiority is available. We propose a solution based on ranking the
      quantitative outcome and assigning worst rank scores to the patients without
      quantitative outcome because of death. Based on this, we derive power formulae
      for a noninferiority test in the presence of death-censored observations,
      considering settings with and without ties. The approach is illustrated for an
      exemplary clinical trial in pulmonary embolism. The results there show a
      substantial effect of death on power, also depending on differential effects in
      the two trial arms. Therefore, use of the proposed formulae is advisable whenever
      there is death to be expected before measurement of a quantitative primary
      outcome of interest.

PMID- 30230575
TI  - UBE3A suppresses overnutrition-induced expression of the steatosis target genes
      of MLL4 by degrading MLL4.
AB  - Regulation of the protein stability of epigenetic regulators remains ill-defined
      despite its potential applicability in epigenetic therapies. The histone H3
      lysine 4-methyltransferase MLL4 is an epigenetic transcriptional coactivator that
      directs overnutrition-induced obesity and fatty liver formation, and Mll4+/- mice
      are resistant to both. Here we show that the E3 ubiquitin ligase UBE3A targets
      MLL4 for degradation thereby suppressing high fat diet (HFD)-induced expression
      of the hepatic steatosis target genes of MLL4. In contrast to Mll4+/- mice,
      Ube3a+/- mice are hypersensitive to HFD-induced obesity and fatty liver
      development. Ube3a+/- ;Mll4+/- mice lose this hypersensitivity, supporting roles
      of increased MLL4 levels in both phenotypes of Ube3a+/- mice. Correspondingly,
      our comparative studies with wild-type, Ube3a+/- and Ube3a-/- and UBE3A
      overexpressing transgenic mouse livers demonstrate inverse-correlation of UBE3A
      protein levels with MLL4 protein levels, expression of the steatosis target genes
      of MLL4, and their decoration by H3-lysine 4-monomethylation, a surrogate marker
      for the epigenetic action of MLL4. Therefore, UBE3A indirectly exerts an
      epigenetic regulation of obesity and steatosis by degrading MLL4. This UBE3A-MLL4
      regulatory axis provides a potential therapeutic venue for treating various MLL4
      directed pathogeneses, including obesity and hepatic steatosis. This article is
      protected by copyright. All rights reserved.

PMID- 30230576
TI  - Primary cutaneous diffuse large B-cell lymphoma, leg type, localized in the right
      periorbital region.

PMID- 30230577
TI  - The missing middle of sickle therapeutics: Multi-agent therapy, targeting risk,
      using biomarkers.

PMID- 30230578
TI  - Epidemiology of pyoderma gangrenosum in Japanese patients by questionnaire
      survey.

PMID- 30230579
TI  - Distant recurrence of Merkel cell carcinoma after spontaneous regression.

PMID- 30230580
TI  - DNA methylation in breast cancers: Differences based on estrogen receptor status
      and recurrence.
AB  - DNA methylation plays a role in the etiology of primary breast cancers. We
      analyzed paired primary and second breast tumors to elucidate the role of
      methylation in recurrence. Methylation profiles from paired primary and second
      breast tumors of 23 women were assessed using the HumanMethylation450 BeadChip.
      Twelve women had estrogen receptor positive (ERpos) primary and second tumors,
      five had estrogen receptor negative (ERneg) primary and second tumors, and six
      had an ERpos primary tumor but an ERneg second tumor. Stratifying tumors by
      occurrence revealed that the greater methylation previously associated with ERpos
      tumors, is more pronounced in primary tumors than in second tumors. Further,
      ERneg second tumors are more methylated than ERpos second tumors among women who
      had ERpos primary tumors. Pathway analyses using gene lists generated from
      comparisons of methylation in ERpos primary tumors from the paired sets with
      ERpos tumors from six women without recurrences, identified differences between
      groups based on the ER status of the second tumor. Hypermethylated genes of
      significantly enriched pathways were differentially associated with survival. DNA
      methylation profiles of ERpos primary breast tumors support the development and
      use of tumor methylation profiles for stratifying women with breast cancer both
      for prognosis and therapy.

PMID- 30230582
TI  - Anti-PL-12 antibody-positive antisynthetase syndrome with recurrent digital
      ulcers.

PMID- 30230581
TI  - The association of physical activity before and after lymphoma diagnosis with
      survival outcomes.
AB  - The impact of physical activity (PA) on lymphoma survival is not known. The
      association of PA and change in PA with overall (OS), lymphoma-specific (LSS) and
      event-free (EFS) survival was evaluated in a prospective cohort of newly
      diagnosed lymphoma patients (2002-2012). We calculated Leisure Score Indexes
      (mLSI) from the self-reported usual adult PA (baseline) and at 3-years post
      diagnosis (FU3), grouping patients by active vs insufficiently active by the
      American Cancer Society PA guidelines. Associations of PA with survival were
      assessed using hazard ratios (HRs) and 95% confidence intervals (CI) from Cox
      models stratified by lymphoma subtype, adjusted for age, sex, baseline BMI, and
      comorbidity score with change scores further adjusted for baseline PA. Three
      thousand sixty participants were evaluable at baseline and 1371 at FU3. Active
      patients had superior survival from baseline [HR (CI): OS 0.82 (0.72-0.94); LSS
      0.74 (0.61-0.90); EFS 0.92 (0.82-1.02)] and FU3 [HR (CI): OS 0.64 (0.46-0.88);
      LSS 0.32 (0.18-0.59); EFS 0.82 (0.61-1.10)] compared to insufficiently active. An
      increase in mLSI from baseline to FU3 (vs stable mLSI) was associated with
      superior OS (HR = 0.70, CI 0.49-1.00) and LSS (HR = 0.49, CI 0.26-0.94).The
      continuous change in mLSI at FU3 was significantly associated with OS, LSS and
      EFS; maintained across subgroups and appeared linear. Higher PA among lymphoma
      patients at diagnosis and 3 years is significantly associated with OS, LSS, and
      EFS. Increasing PA after diagnosis is significantly associated with improved OS
      and LSS supporting an important role for PA in lymphoma survivorship and the need
      for intervention trials.

PMID- 30230583
TI  - The regulatory roles of VEGF-Notch signaling pathway on aplastic anemia with
      kidney deficiency and blood stasis.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF)-Notch signaling pathway
      plays an important role in aplastic anemia (AA). This study aimed to evaluate the
      regulatory roles of VEGF-Notch signaling pathway on mesenchymal stem cells (MSCs)
      isolated from AA patients with kidney deficiency and blood stasis (KB) (AA MSCs).
      METHODS: Expression of VEGF-Notch signaling related factors, including VEGF,
      VEGFR, Notch-1, Jagged1, Delta-like1, and hes1 was detected in bone marrow (BM)
      tissues and AA MSCs by Western blot analysis. VEGF (100 ng/mL) and gamma
      secretase inhibitor (DAPT) (10 MUM) was used to active and inhibit VEGF-Notch
      signaling in AA MSCs, respectively. After treatment, the proliferation,
      apoptosis, and adipogenic differentiation of AA MSCs was detected by Cell
      Counting Kit-8, flow cytometry, and Oil red O staining, respectively. Lentivirus
      short hairpin RNA (shRNA) were constructed to downregulate Notch-1 and VEGF in
      normal bone marrow mesenchymal stem cells (BMSCs), and the effects of VEGF/Notch
      1 shRNA transfected BMSCs on the proliferation, migration, and angiogenesis of
      human umbilical vein endothelial cells (HUVECs) were evaluated. RESULTS:
      Significantly lower expression of VEGF, VEGFR, Notch-1, Jagged1, Delta-like1, and
      hes1 was revealed in AA BM tissues and AA MSCs when compared with the normal
      control (P < 0.05). The intervention of DAPT significantly inhibited the
      proliferation, and promoted the apoptosis and adipogenic differentiation of AA
      MSCs, while VEGF intervention exhibited opposite results (P < 0.05). Meanwhile,
      the proliferation, migration, and angiogenesis of HUVECs were significantly
      promoted by normal BMSCs, while inhibited by VEGF/Notch-1 shRNA transfected BMSCs
      (P < 0.05). CONCLUSION: The activation of VEGF-Notch signaling pathway may be a
      potential therapeutic target for AA with KB.

PMID- 30230584
TI  - Successful treatment of refractory juvenile generalized pustular psoriasis with
      secukinumab monotherapy: A case report and review of published work.
AB  - Juvenile generalized pustular psoriasis (GPP) is rare and often resistant to
      conventional systemic therapy such as methotrexate, retinoic acid and cyclosporin
      A. GPP can be induced by deficiency of interleukin (IL)-36 receptor antagonist
      (DITRA). No standardized guidelines are available for juvenile GPP or DITRA, and
      a uniformly safe and effective biologic agent has not been identified. However,
      multiple biologics approved for use in plaque-type psoriasis have also been used
      in GPP. Herein, we report a case of a 6-year-old Taiwanese boy with GPP and
      homozygous mutation at c.115+6T>C within the IL-36 receptor antagonist (IL36RN)
      gene, who was treated successfully with secukinumab after failure of prior
      methotrexate, acitretin, cyclosporin A, etanercept and adalimumab. Similar to two
      previously reported non-adult cases of GPP successfully treated with secukinumab,
      our case also demonstrated a history of repeated treatment failures with several
      conventional oral systemic agents and biologics. Different from these two cases,
      however, ours is the first of juvenile GPP successfully treated with secukinumab
      monotherapy, without using other systemic agent concurrently during the use of
      secukinumab.

PMID- 30230585
TI  - Identification and validation of l-asparaginase as a potential metabolic target
      against Mycobacterium tuberculosis.
AB  - Multidrug-resistant Mycobacterium tuberculosis (Mtb) has emerged as a major
      health challenge, necessitating the search for new molecular targets. A secretory
      amidohydrolase, l-asparaginase of Mtb (MtA), originally implicated in nitrogen
      assimilation and neutralization of acidic microenvironment inside human alveolar
      macrophages, has been proposed as a crucial metabolic enzyme. To investigate
      whether this enzyme could serve as a potential drug target, it was studied for
      structural details and active site-specific inhibitors were tested on cultured
      Mycobacterial strain. The structural details of MtA obtained through comparative
      modeling and molecular dynamics simulations provided insights about the
      orchestration of an alternate reaction mechanism at the active site. This was
      contrary to the critical Tyr flipping mechanism reported in other asparaginases.
      We report the novel finding of Tyr to Val replacement in catalytic triad I along
      with the structural reorganization of a beta-hairpin loop upon substrate binding
      in MtA active site. Further, 5 MtA-specific, active-site-based inhibitors were
      obtained by following a rigorous differential screening protocol. When tested on
      Mycobacterium culture, 3 of these, M3 (ZINC 4740895), M26 (ZINC 33535), and
      doxorubicin showed promising results with inhibitory concentrations (IC 50 ) of
      431, 100, and 56 uM, respectively. Based on our findings and considering stark
      differences with human asparaginase, we project MtA as a promising molecular
      target against which the selected inhibitors may be used to counteract Mtb
      infection effectively.

PMID- 30230586
TI  - MED12 somatic mutations encompassing exon 2 associated with benign breast
      fibroadenomas and not breast carcinoma in Indian women.
AB  - Fibroadenoma is the most common type of benign breast tumor, accounting for 90%
      of benign lesions in India. Somatic mutations in the mediator complex subunit 12
      (MED12) gene play a critical role in fibroepithelial tumorigenesis. The current
      study evaluated the hotspot region encompassing exon 2 of the MED12 gene, in
      benign and malignant breast tumor tissue from women who presented for breast lump
      evaluation. A total of 100 (80 fibroadenoma and 20 breast cancer) samples were
      analyzed by polymerase chain reaction-Sanger sequencing. Sequence variant
      analysis showed that 68.75% of nucleotide changes were found in exon 2 and the
      remaining in the adjacent intron 1. Codon 44 was implicated as a hotspot mutation
      in benign tumors, and 86.36% of the identified mutations involved this codon. An
      in silico functional analysis of missense mutations using consensus scoring
      sorting intolerant from tolerant (SIFT), SIFT seq, Polyphen2, Mutation Assessor,
      SIFT transFIC, Polyphen2 transFIC, Mutation Assesor transFIC, I-Mutant, DUET, PON
      PS, SNAP2, and protein variation effect analyzer] revealed that apart from
      variants involving codon 44 (G44S; G44H), others like V41A and E55D were also
      predicted to be deleterious. Most of the missense mutations appeared in the loop
      region of the MED12 protein, which is expected to affect its functional
      interaction with cyclin C-CDK8/CDK19, causing loss of mediator-associated cyclin
      depended kinase (CDK) activity. These results suggest a key role of MED12 somatic
      variations in the pathogenesis of fibroadenoma. For the first time, it was
      demonstrated that MED12 sequence variations are present in benign breast tumors
      in the south Indian population.

PMID- 30230587
TI  - CCL17-CCR4 axis promotes metastasis via ERK/MMP13 pathway in bladder cancer.
AB  - As an important chemokine receptor, the role of CCR4 in the progression of
      bladder cancer (BC) remains unknown. In this study, we have shown that CCR4
      expression was upregulated in bladder carcinoma tissues compared with adjacent
      nontumor tissues. Kaplan-Meier survival analysis revealed that CCR4 expression
      was an independent prognostic risk factor in BC patients, and the addition of
      CCL17 induced CCR4 production and promoted migration and invasion of BC cells. In
      addition, CCR4 knockdown significantly attenuated the migratory and invasive
      capabilities of BC cells. Mechanistically, CCL17-CCR4 axis is involved in ERK1/2
      signaling and could mediate the migration and invasion of BC cells by regulating
      MMP13 activation. This study suggests that CCR4 might represent a promising
      prognostic biomarker and a potential therapeutic option for BC.

PMID- 30230588
TI  - Compressed sensing acceleration of biexponential 3D-T1rho relaxation mapping of
      knee cartilage.
AB  - PURPOSE: Use compressed sensing (CS) for 3D biexponential spin-lattice relaxation
      time in the rotating frame (T1rho ) mapping of knee cartilage, reducing the total
      scan time and maintaining the quality of estimated biexponential T1rho parameters
      (short and long relaxation times and corresponding fractions) comparable to fully
      sampled scans. METHODS: Fully sampled 3D-T1rho -weighted data sets were
      retrospectively undersampled by factors 2-10. CS reconstruction using 12
      different sparsifying transforms were compared for biexponential T1rho -mapping
      of knee cartilage, including temporal and spatial wavelets and finite
      differences, dictionary from principal component analysis (PCA), k-means singular
      value decomposition (K-SVD), exponential decay models, and also low rank and low
      rank plus sparse models. Synthetic phantom (N = 6) and in vivo human knee
      cartilage data sets (N = 7) were included in the experiments. Spatial filtering
      before biexponential T1rho parameter estimation was also tested. RESULTS: Most CS
      methods performed satisfactorily for an acceleration factor (AF) of 2, with
      relative median normalized absolute deviation (MNAD) around 10%. Some sparsifying
      transforms, such as low rank with spatial finite difference (L + S SFD),
      spatiotemporal finite difference (STFD), and exponential dictionaries (EXP)
      significantly improved this performance, reaching MNAD below 15% with AF up to
      10, when spatial filtering was used. CONCLUSION: Accelerating biexponential 3D
      T1rho mapping of knee cartilage with CS is feasible. The best results were
      obtained by STFD, EXP, and L + S SFD regularizers combined with spatial
      prefiltering. These 3 CS methods performed satisfactorily on synthetic phantom as
      well as in vivo knee cartilage for AFs up to 10, with median error below 15%.

PMID- 30230589
TI  - Optimization of the spatial modulation function of vessel-encoded pseudo
      continuous arterial spin labeling and its application to dynamic angiography.
AB  - PURPOSE: In vessel-encoded pseudo-continuous arterial spin labeling (ve-pCASL),
      vessel-selective labeling is achieved by modulation of the inversion efficiency
      across space. However, the spatial transition between the labeling and control
      conditions is rather gradual, which can cause partial labeling of vessels,
      reducing SNR-efficiency and necessitating complex postprocessing to decode the
      vessel-selective signals. The purpose of this study is to optimize the pCASL
      labeling parameters to obtain a sharper spatial inversion profile of the labeling
      and thereby minimizing the risk of partial labeling of untargeted arteries.
      METHODS: Bloch simulations were performed to investigate how the inversion
      profile was influenced by the pCASL labeling parameters: the maximum (Gmax ) and
      mean (Gmean ) labeling gradient were varied for ve-pCASL with unipolar and
      bipolar gradients. The findings in the simulation study were subsequently
      confirmed in an in vivo volunteer study. Moreover, conventional and optimized
      settings were compared for 4D-MRA using four-cycle Hadamard ve-pCASL; the
      visualization of arteries and the presence of the partial labeling were assessed
      by an expert observer. RESULTS: When using unipolar gradient, lower Gmean
      resulted in a steeper spatial transition, whereas the width of the control region
      was broader for higher Gmax . The in vivo study confirmed these findings. When
      using bipolar gradients, the control region was always very narrow. Qualitative
      comparison of the 4D-MRA demonstrated lower occurrence of partial labeling when
      using the optimized gradient parameters. CONCLUSION: The shape of the ve-pCASL
      inversion profile can be optimized by changing Gmean and Gmax to reduce partial
      labeling of untargeted arteries.

PMID- 30230591
TI  - Ghost writing and conflict of interest - Editor's comments.

PMID- 30230590
TI  - Long noncoding RNAs antisense noncoding RNA in the INK4 locus (ANRIL) correlates
      with lower acute exacerbation risk, decreased inflammatory cytokines, and mild
      GOLD stage in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: We aimed to assess the predictive value of long noncoding RNAs
      antisense noncoding RNA in the INK4 locus (lncRNAs ANRIL) for acute exacerbation
      of chronic obstructive pulmonary disease (COPD) and evaluate its correlation with
      inflammatory cytokines as well as the Global Initiative for Chronic Obstructive
      Lung Disease (GOLD) stage in COPD patients. METHODS: A total of 136 acute
      exacerbations of COPD (AECOPD) patients, 138 stable COPD patients, and 140
      healthy controls (HCs) were consecutively recruited, and plasma samples were
      collected. Real-time polymerase chain reaction was used to detect lncRNA ANRIL
      expression. Enzyme-linked immunosorbent assay was performed to detect
      inflammatory cytokines expressions. RESULTS: LncRNA ANRIL expression was lower in
      AECOPD patients compared with stable COPD patients and HCs (Both P < 0.001).
      Receiver operating characteristic curves revealed lncRNA ANRIL could distinguish
      AECOPD patients from HCs (area under curve (AUC):0.700, 95% CI: 0.638-0.762) and
      stable COPD patients (AUC: 0.659, 95% CI: 0.594-0.724). For inflammatory
      cytokines, lncRNA ANRIL expression was negatively correlated with TNF-alpha (P <
      0.001), IL-1beta (P = 0.015), IL-8 (P = 0.008), IL-17A (P = 0.002), and LTB-4 (P
      = 0.004) in AECOPD patients, while it was negatively correlated with TNF-alpha (P
      = 0.049), IL-1beta (P = 0.005), IL-17A (P = 0.030), and LTB-4 (P = 0.011) in
      stable COPD patients. Furthermore, lncRNA ANRIL expression negatively correlated
      with GOLD stage in AECOPD patients (P = 0.001), but not in stable COPD patients
      (P = 0.131). CONCLUSION: LncRNA ANRIL associates with lower acute exacerbation
      risk, decreased inflammatory cytokines, and mild GOLD stage in COPD patients.

PMID- 30230592
TI  - Long noncoding RNA DGCR5 represses hepatocellular carcinoma progression by
      inactivating Wnt signaling pathway.
AB  - Increasing studies have indicated that long noncoding RNAs (lncRNAs) exert
      important roles in hepatocellular carcinoma (HCC). Therefore, it is of great
      significance to identify the dysregulated lncRNAs in HCC. According to the
      previous reports, it has been suggested that DiGeorge syndrome critical region
      gene 5 (DGCR5) might participate in HCC and can serve as potential biomarker for
      HCC. In our current study, we concentrated on the biological function and roles
      of lncRNA-DGCR5 in HCC. It was indicated that DGCR5 was decreased in HCC tissues
      and HCC cells including HepG2, Hep3B, MHCC-97L, SNU-449, and SNU-182 cells
      compared with the normal human liver cell line LO2. Overexpression of DGCR5 was
      able to restrain HCC growth, migration, and invasion capacity in HepG2 and SNU
      449 cells. In addition, whether lncRNA-DGCR5 can regulate Wnt/beta-catenin
      pathway during HCC progression is unclear. In our study, it was found that
      upregulation of DGCR5 inactivated Wnt signaling pathway through inhibiting beta
      catenin, cyclin D1 and increasing GSK-3beta levels. Subsequently, in vivo tumor
      xenografts were established using HepG2 cells to investigate the function of
      DGCR5 in HCC development. Inconsistent with the in vitro findings, increase of
      DGCR5 dramatically suppressed HCC tumor progression in vivo. Taken these
      together, it was uncovered in our research that DGCR5 could play tumor
      suppressive role by targeting Wnt signaling in HCC progression.

PMID- 30230593
TI  - Trachelas tranquillus envenomation with presumed bacterial superinfection in a
      child.
AB  - A 27-month-old girl with a history of congenital myopathy presented with two
      indurated, pink plaques involving the right arm and left thigh. Closer
      examination identified central puncta within these plaques, which reportedly
      occurred at sites of witnessed arachnid bites. After confirmation of the spider
      species as Trachelas tranquillus, she was treated to address cutaneous
      inflammation and suspected superinfection using oral and topical antibiotics as
      well as topical corticosteroid resulting in prompt resolution of her lesions.
      Trachelas tranquillus should be considered as a possible source of inflammatory
      spider bites that can become superinfected.

PMID- 30230594
TI  - Melatonin reprogramming of gut microbiota improves lipid dysmetabolism in high
      fat diet-fed mice.
AB  - Melatonin has been shown to improve lipid metabolism and gut microbiota
      communities in animals and humans; however, it remains to know whether melatonin
      prevents obesity through gut microbiota. Here, we found that high-fat diet
      promoted the lipid accumulation and intestinal microbiota dysbiosis in mice,
      while oral melatonin supplementation alleviated the lipid accumulation and
      reversed gut microbiota dysbiosis, including the diversity of intestinal
      microbiota, relative abundances of Bacteroides and Alistipes, and functional
      profiling of microbial communities, such as energy metabolism, lipid metabolism,
      and carbohydrate metabolism. Interestingly, melatonin failed to alleviate the
      high-fat-induced lipid accumulation in antibiotic-treated mice; however,
      microbiota transplantation from melatonin-treated mice alleviated high-fat diet
      induced lipid metabolic disorders. Notably, short-chain fatty acids were
      decreased in high-fat diet-fed mice, while melatonin treatment improved the
      production of acetic acid. Correlation analysis found a marked correlation
      between production of acetic acid and relative abundances of Bacteroides and
      Alistipes. Importantly, sodium acetate treatment also alleviated high-fat diet
      induced lipid metabolic disorders. Taken together, our results suggest that
      melatonin improves lipid metabolism in high-fat diet-fed mice, and the potential
      mechanisms may be associated with reprogramming gut microbiota, especially,
      Bacteroides and Alistipes-mediated acetic acid production. Future studies are
      needed for patients with metabolic syndrome to fully understand melatonin's
      effects on body weight and lipid profiles and the potential mechanism of gut
      microbiota.

PMID- 30230595
TI  - Dual-step iterative temperature estimation method for accurate and precise fat
      referenced PRFS temperature imaging.
AB  - PURPOSE: The aim of this study was to propose dual-step iterative temperature
      estimation (DITE) of a fat-referenced proton resonance frequency shift (PRFS)
      method to improve both the accuracy and precision of temperature estimations in
      fat-containing tissues. METHODS: A fat-water signal model with multiple fat peaks
      was used to simultaneously estimate the temperature, fat/water intensity and 
      RESULTS: In fat/water phantom experiment with a smooth temperature profile, the
      temperatures estimated by DITE are consistent with the thermometer results and
      present a better accuracy and precision than those of previous fat-referenced
      proton resonance frequency shift methods. In the brown adipose tissue heating
      experiment, the average mean error, SD, and RMS error were -0.08oC, 0.46oC, and
      0.56oC, respectively, over all of the measurements within the region of interest.
      CONCLUSION: Our proposed DITE method improves both the accuracy and precision of
      temperature measurements in tissues with fat fractions between 20% and 80% under
      smooth distribution of the temperature profile and represents a simple fat
      referenced thermometry method.

PMID- 30230596
TI  - Translation and validation of the Nepalese version of the Geriatric Oral Health
      Assessment Index.
AB  - OBJECTIVE: To translate and validate the Geriatric Oral Health Assessment Index
      (GOHAI) (Nepali version) from original English version. BACKGROUND: Growing
      numbers of elderly people have problems in different aspects of oral health
      increasing the demand for dental care services among them GOHAI may be one of the
      effective means of gathering information on oral health problems of the elderly
      people. MATERIALS AND METHODS: A total of 168 individuals >=60 years from seven
      old-age homes located in Eastern Nepal were included in the study. The Nepali
      version of GOHAI was translated and validated. RESULTS: A total of 168 elderly
      people (79 male and 89 female participants) completed GOHAI questionnaire. The
      mean age (+/-SD) of the participants was 72.49 (+/-10.00) years. The mean GOHAI
      score (+/-SD) was 42.29 (+/-6.93) and ranged from 17 to 59. Cronbach's alpha
      coefficient for the Nepali version of GOHAI (GOHAI-N) was 0.74, which is
      categorised as very good agreement. Analysis of discriminant validity showed that
      lower mean GOHAI score was seen in study participants with more number of missing
      and decayed teeth. However, those who had more than one filled surface had higher
      mean GOHAI score. CONCLUSION: The Nepali version of the GOHAI exhibited
      acceptable reliability and validity when used for older people residing in old
      age homes. The GOHAI-N showed good consistency and homogeneity among the items.

PMID- 30230597
TI  - Identification specific miRNA in t(4;14) multiple myeloma based on miRNA-mRNA
      expressing profile correlation analysis.
AB  - BACKGROUND: Multiple myeloma (MM) is a common malignancy belonging to the
      hematological system. The translocation t(4;14)(p16.3;q32.3) is a critical
      cytogenetic change of MM, which is presenting a poor prognosis. The specific
      microRNAs (miRNAs) that are involved in t(4;14) myeloma are still unknown. Thus,
      the main purpose of this research was to identify specific miRNAs in t(4;14)
      positive myeloma. METHODS: The expression profiles of miRNA and messenger RNA
      (mRNA) in t(4; 14) positive and negative samples were obtained from the gene
      expression omnibus data series. The miRNA-mRNA regulatory network was constructed
      based on two self-defined regulation models. Subsequently, we performed the
      topology analysis for mining the hub genes, and Pearson's correlation coefficient
      analysis was used to calculate the relevance of the hub genes and specific
      miRNAs. RESULTS: Thirteen differentially expressed miRNAs and 206 differential
      mRNAs were extracted between t(4;14) positive group and negative group. The
      network consisted of 8 miRNAs and 154 mRNAs in 2 reverse regulated models, which
      showed a total of 485 interactions, including 376 cis-regulated and 109 trans
      regulated relationships. The miR-125a-3p, miR-125a-5p, miR-99b-5p, and let-7e
      were powerful miRNAs correlating with the FGFR3, MAP1B, MYRIP, and CDC42BPA under
      the relevance analysis in the subnetwork. CONCLUSION: In our study, a distinctive
      correlation analysis of miRNA-mRNA was established to excavate specific miRNAs
      and hub target mRNAs in patients with t(4;14), but it was only a matter of
      theoretical principles. The further experimental explorations are needed to
      confirm valuable diagnostic and therapeutic symbols specific associated with
      t(4;14) in the future.

PMID- 30230598
TI  - Physical exercise prevents alterations in purinergic system and oxidative status
      in lipopolysaccharide-induced sepsis in rats.
AB  - Sepsis is a generalized infection that involves alterations in inflammatory
      parameters, oxidant status, and purinergic signaling in many tissues. Physical
      exercise has emerged as a tool to prevent this disease because of its anti
      inflammatory and antioxidant properties. Thus, in this study, we investigated the
      effects of physical exercise on preventing alterations in purinergic system
      components, oxidative stress, and inflammatory parameters in lipopolysaccharide
      (LPS)-induced sepsis in rats. Male Wistar rats were divided into four groups:
      control, exercise (EX), LPS, and EX+LPS. The resisted physical exercise was
      performed for 12 weeks on a ladder with 1 m height. After 72 hours of the last
      exercise session, the animals received 2.5 mg/kg of LPS for induction of sepsis,
      and after 24 hours, lungs and blood samples were collected for analysis. The
      results showed that the exercise protocol used was able to prevent, in septic
      animals: (1) the increase in body temperature; (2) the increase of lipid
      peroxidation and reactive species levels in the lung, (3) the increase in
      adenosine triphosphate levels in serum; (4) the change in the activity of the
      enzymes ectonucleotidases in lymphocytes, partially; (5) the change in the
      density of purinergic enzymes and receptors in the lung, and (6) the increase of
      IL-6 and IL-1beta gene expression. Our results revealed the involvement of
      purinergic signaling and oxidative damage in the mechanisms by which exercise
      prevents sepsis aggravations. Therefore, the regular practice of physical
      exercise is encouraged as a better way to prepare the body against sepsis
      complications.

PMID- 30230599
TI  - T2 relaxation time bias in gagCEST at 3T and 7T: comparison of saturation
      schemes.
AB  - PURPOSE: To characterize the effects of water T2 relaxation time in the
      glycosaminoglycan chemical exchange saturation transfer method (gagCEST) and
      compare them between 3T and 7T as well as between various saturation schemes.
      METHODS: Simulations and a phantom experiment were conducted at 3T and 7T in a
      range of water T2 values and GAG concentrations using various saturation schemes.
      For both simulations and MRI measurements, unsaturated signal as well as the
      saturated Z-spectrum were generated, and the magnetization transfer ratio
      asymmetry at 1 parts per million was used as a measure of the gagCEST effect
      size. RESULTS: The simulations and phantom experiment results showed a clear GAG
      concentration and T2 dependence of the gagCEST effect size. Whereas the gagCEST
      effect size was much larger at 7T, the impact of the T2 bias was more pronounced
      at 3T. The saturation train length, duty cycle, and average B1 all had clear
      impact on both the gagCEST effect size and T2 bias. CONCLUSION: The water T2
      relaxation is important to consider in gagCEST, especially at 3T. The T2
      differences can introduce a pronounced bias, which may obscure the gagCEST effect
      when using low duty cycles and long saturation trains.

PMID- 30230600
TI  - Long noncoding RNA HEIH promotes the proliferation and metastasis of non-small
      cell lung cancer.
AB  - OBJECTIVES: This study is aimed to explore the functions of long noncoding RNA
      (lncRNA) HEIH on the proliferation as well as metastasis of non-small cell lung
      cancer (NSCLC). METHODS: HEIH was shown to be increased in NSCLC by a microarray
      study on lncRNA profiling. We detected the expression of HEIH in different human
      NSCLC lines and tissues by quantitative real-time PCR. After gain- and loss-of
      function approaches in A549 and Calu-1 cells, 3-(4,5-dimethyl-2-thiazolyl)-2,5
      diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide (MTT) assays
      and a colony formation assay were applied to test the proliferative activity of
      cells, and the apoptosis of cells was measured by flow cytometry. Western blot
      analysis was used to evaluate the protein expression, and the effects of lncRNA
      HEIH on cell migratory and invasive abilities of A549 and Calu-1 cells were
      evaluated using wound healing and transwell assays. RESULTS: In our study, we
      confirmed the elevated expression of HEIH in NSCLC tissues and cell lines
      compared with the normal ones. After constructing A549 and Calu-1 cells with
      altered HEIH expression by transient transfection, cell viability was found to be
      positively regulated by the HEIH level. Moreover, overexpression of HEIH
      accelerated the cell migrating rate and increased the invasive cell number
      according to the results of a wound healing assay and transwell assay.
      CONCLUSIONS: HEIH could accelerate the proliferation and metastasis of NSCLC,
      providing a novel therapeutic target for clinical treatment.

PMID- 30230601
TI  - Interaction of long noncoding RNA MEG3 with miRNAs: A reciprocal regulation.
AB  - The competitive endogenous RNA (ceRNA) hypothesis suggests that a long noncoding
      RNA (lncRNA) can function as sinks for pools of microRNAs (miRNAs); thereby, in
      the presence of ceRNA, messenger RNAs (mRNAs) targeted by specific miRNAs can
      liberate and translate to protein. Maternally expressed gene 3 (MEG3) is a
      lncRNA, which its expression has been detected in various normal tissues, while
      it is lost or downregulated in human tumors. The MEG3 is an imprinted gene which,
      is methylated and suppressed by DNA methyltransferases (DNMTs) family. Also,
      miRNAs are involved in the regulation of MEG3 gene expression. Interestingly, the
      lncRNA MEG3 (lnc-MEG3), as a ceRNA affects various cell processes such as
      proliferation, apoptosis, and angiogenesis by sponging miRNAs. These miRNAs, in
      turn, regulate different mRNAs in different pathways. This review focuses on the
      interaction between lnc-MEG3 and experimentally validated miRNAs. In addition,
      the discussion supplemented by some data obtained from mirPath (v.3) and TarBase
      (v.8) databanks to provide more details about the pathways affected by this
      ceRNA.

PMID- 30230602
TI  - Oral care as a life course project: A qualitative grounded theory study.
AB  - OBJECTIVE: To report on a theory to explain the oral health of older people over
      the life course. BACKGROUND: The study of ageing has burgeoned into a complex
      interdisciplinary field of research, yet there are few studies in oral health
      from the perspective of older people that bridge the gap between sociology and
      oral health related research. METHODS: A grounded theory study involving a
      convenience sample of 15 men and 28 women aged between 65 and 91 years across
      different levels of education. Data were subjected to grounded theory analysis
      using QSR NVivo 11.0 and where relevant phenomenological theory. RESULTS:
      Participants conceived of oral care as a life course project that resulted from
      an active plan to keep one's teeth into older age. This involved accessing the
      social world of dentistry, holding appropriate values, understanding the
      associated personality types, social practices, goals and outcomes. The life
      course project is a social project supported by social institutions. It involves
      ideas about appropriate ageing including how oral health is to be managed at
      different stages in the life course. The degree to which individuals are able to
      participate in this project is determined by both individual and social factors.
      CONCLUSIONS: The theory explains why the loss of a single tooth might be
      experienced as traumatic but also why older people adapt to their changing oral
      health. Oral health in older age represented a lifetime's investment in oral
      care. Future health policies should consider this lifetime investment when
      considering care for older people.

PMID- 30230604
TI  - Ageing patients in forensic psychiatric settings: A review of the literature.
AB  - OBJECTIVES: The prevalence of ageing patients in forensic psychiatric settings is
      increasing. However, limited research has reported around this population. The
      aim of this scoping review is to synthesise the current evidence around ageing
      forensic psychiatric patients. METHODS: The literature was searched through four
      databases and Google searches. The identified outputs were screened for
      suitability and assessed for quality. Quantitative data were extracted and
      analysed on SPSS; qualitative data were extracted and analysed onto NVivo.
      RESULTS: Seven studies were included in the review. Quantitative results reported
      around demographics, service contact, offending patterns, mental, and physical
      health of ageing patients. Qualitative findings focused on age-friendliness of
      services, staff-patient rapport, activities, security issues, and discharge
      planning. CONCLUSIONS: Ageing forensic psychiatric patients present with complex
      and unique needs in relation to treatment, activities, mental, physical, and
      support. Further research looking at individual patients' needs is paramount to
      inform policy development and good practice in this area.

PMID- 30230603
TI  - Mapping electrical properties heterogeneity of tumor using boundary informed
      electrical properties tomography (BIEPT) at 7T.
AB  - PURPOSES: To develop and evaluate a boundary informed electrical properties
      tomography (BIEPT) technique for high-resolution imaging of tumor electrical
      properties (EPs) heterogeneity on a rodent tumor xenograft model. METHODS: Tumor
      EP distributions were inferred from a reference area external to the tumor, as
      well as internal EP spatial variations derived from a plurality of relative
      transmit B1 measurements at 7T. Edge sparsity constraint was enforced to enhance
      numerical stability. Phantom experiments were performed to determine the imaging
      accuracy and sensitivity for structures of various EP values, as well as
      geometrical sizes down to 1.5 mm. Numerical simulation of a realistic rodent
      model was used to quantify the algorithm performance in the presence of noise.
      Eleven athymic rats with human breast cancer xenograft were imaged in vivo, and
      representative pathological samples were acquired for comparison. RESULTS:
      Reconstructed EPs of the phantoms correspond well to the ground truth acquired
      from dielectric probe measurements, with the smallest structure reliably
      detectable being 3 mm. EPs heterogeneity inside a tumor is successfully retrieved
      in both simulated and experimental cases. In vivo tumor imaging results
      demonstrate similar local features and spatial patterns to anatomical MRI and
      pathological slides. The imaged conductivity of necrotic tissue is higher than
      that of viable tissues, which agrees with our expectation. CONCLUSION: BIEPT
      enables robust detection of tumor EPs heterogeneity with high accuracy and
      sensitivity to small structures. The retrieved quantitative EPs reflect tumor
      pathological features (e.g., necrosis). These results provide strong rationale to
      further expand BIEPT studies toward pathological conditions where EPs may yield
      valuable, non-invasive biomarkers.

PMID- 30230605
TI  - White matter intercompartmental water exchange rates determined from detailed
      modeling of the myelin sheath.
AB  - PURPOSE: Magnetization exchange (ME) between hydrogen protons of water and large
      molecules (semisolids [SS]) in lipid bilayers is an important factor in MRI
      signal generation and can be exploited to study white matter pathology. Current
      models used to quantify ME in white matter generally consider water to reside in
      1 or 2 distinct compartments, ignoring the complexities of the myelin sheath's
      multicompartment structure of alternating myelin SS and myelin water (MW) layers.
      Here, we investigated the effect of this by fitting ME data obtained from human
      brain at 7 T with a multilayer model of myelin. METHODS: A multi-echo acquisition
      for a T2 * -based separation of MW from other water signals was combined with
      various preparation pulses to change the (relative) state of the SS and water
      pools and analyzed by fitting with a multilayer exchange model. RESULTS: The
      estimated lifetime within a single MW layer was 260 us, corresponding to a lipid
      bilayer permeability of 6.7 um/s. The magnetization lifetime of the aggregate of
      all MW was estimated at 13 ms, shorter than previously reported values in the
      range of 40 to 140 ms. CONCLUSION: Contrary to expectations and previous reports,
      ME between protons in myelin SS and water is not limited by the myelin sheath but
      rather by the exchange between SS and water protons. The analysis of ME contrast
      should account for the relatively short MW lifetime and affects the
      interpretation of tissue compartmentalization from MRI contrasts such as T1 - and
      diffusion-weighting.

PMID- 30230606
TI  - Segmentation of left ventricle in late gadolinium enhanced MRI through 2D-4D
      registration for infarct localization in 3D patient-specific left ventricular
      model.
AB  - PURPOSE: To evaluate a 2D-4D registration-cum-segmentation framework for the
      delineation of left ventricle (LV) in late gadolinium enhanced (LGE) MRI and for
      the localization of infarcts in patient-specific 3D LV models. METHODS: A 3-step
      framework was proposed, consisting of: (1) 3D LV model reconstruction from motion
      corrected 4D cine-MRI; (2) Registration of 2D LGE-MRI with 4D cine-MRI; (3) LV
      contour extraction from the intersection of LGE slices with the LV model. The
      framework was evaluated against cardiac MRI data from 27 patients scanned within
      6 months after acute myocardial infarction. We compared the use of local
      Pearson's correlation (LPC) and normalized mutual information (NMI) as similarity
      measures for the registration. The use of 2 and 6 long-axis (LA) cine-MRI scans
      was also compared. The accuracy of the framework was evaluated using manual
      segmentation, and the interobserver variability of the scar volume derived from
      the segmented LV was determined using Bland-Altman analysis. RESULTS: LPC
      outperformed NMI as a similarity measure for the proposed framework using 6 LA
      scans, with Hausdorrf distance (HD) of 1.19 +/- 0.53 mm versus 1.51 +/- 2.01 mm
      (endocardial) and 1.21 +/- 0.48 mm versus 1.46 +/- 1.78 mm (epicardial),
      respectively. Segmentation using 2 LA scans was comparable to 6 LA scans with a
      HD of 1.23 +/- 0.70 mm (endocardial) and 1.25 +/- 0.74 mm (epicardial). The
      framework yielded a lower interobserver variability in scar volumes compared with
      manual segmentation. CONCLUSION: The framework showed high accuracy and
      robustness in delineating LV in LGE-MRI and allowed for bidirectional mapping of
      information between LGE- and cine-MRI scans, crucial in personalized model
      studies for treatment planning.

PMID- 30230607
TI  - Hepatitis E virus genotype 3 is a common finding in liver-transplanted patients
      undergoing liver biopsy for elevated liver enzymes with a low De Ritis ratio and
      suspected acute rejection: A real-world cohort.
AB  - BACKGROUND: Hepatitis E virus (HEV) infection is a potential reason for elevated
      liver enzymes after liver transplantation (LT). Our aim was to analyze a real
      world cohort of LT patients, who underwent liver biopsy for elevated
      transaminases and suspected acute rejection, to evaluate frequency of post
      transplant HEV infection. PATIENTS: Data from 160 liver biopsies were analyzed.
      Seventy-one patients were biopsied on schedule after LT without elevated liver
      enzymes. A subgroup of 25 patients with elevated liver enzymes and suspected
      rejection was chosen for further analysis. Patient demographics and data were
      retrieved from a clinical database, patients' charts, and reports. RESULTS:
      Hepatitis E virus infection was diagnosed in five of 25 patients with suspected
      acute rejection (20%). HEV genotype 3 was detected in three of the five HEV
      infected patients. Patients with HEV infection showed higher ALT levels (P =
      0.014), lower De Ritis ratio (P = 0.021), and more frequent glucocorticoid
      therapy (P = 0.012) compared to HEV-negative patients. CONCLUSION: We found a
      rate of 20% HEV infections in LT patients undergoing liver biopsy for elevated
      liver enzymes and suspected acute rejection. These data indicate the necessity
      for HEV testing in all LT patients with elevated liver enzymes and suspected
      acute rejection.

PMID- 30230608
TI  - Resilience attenuates the association between neurocognitive functioning and
      everyday functioning in individuals aging with HIV in the Deep South.
AB  - OBJECTIVES: Adults aging with HIV are at risk for poorer neurocognitive and daily
      functioning. Identifying factors to protect such outcomes is a significant
      research priority. The aim of this study was to explore the role of resilience in
      cognitive and everyday functioning in a largely African American and low
      socioeconomic status sample of adults and older adults with HIV in the Deep
      South. METHODS/DESIGN: In this cross-sectional study 100 HIV+ middle-aged and
      older adults (range 40-73; 61% aged 50+) completed a comprehensive neurocognitive
      battery along with self-reported measures of resilience and everyday functioning.
      RESULTS: Higher resilience was associated with better global neurocognitive
      functioning (rho = 0.31, P < 0.01), as well as better functioning in all domains
      (verbal fluency, executive functioning, speed of information processing,
      learning, working memory) except recall and motor skills. Resilience was also
      significantly associated with instrumental activities of daily living (IADL)
      dependence, with lower resilience observed in those with IADL dependence compared
      with those who were IADL independent (P < 0.01). In a multiple regression
      adjusting for data-driven covariates (verbal IQ, income, depression), and global
      neurocognitive impairment, resilience was the only significant (P = 0.02)
      correlate of IADL dependence. A follow-up mediation showed that the direct
      relationship between neurocognitive functioning and IADL declines was fully
      attenuated after accounting for shared variance with resilience. CONCLUSIONS:
      Resilience is associated with better cognitive and functional outcomes in people
      aging with HIV. While further work is needed to understand these associations
      over time, results suggest interventions to build resilience may promote
      successful aging in this vulnerable population.

PMID- 30230609
TI  - Non-contrast enhanced simultaneous 3D whole-heart bright-blood pulmonary veins
      visualization and black-blood quantification of atrial wall thickness.
AB  - PURPOSE: Pre-interventional assessment of atrial wall thickness (AWT) and of
      subject-specific variations in the anatomy of the pulmonary veins may affect the
      success rate of RF ablation procedures for the treatment of atrial fibrillation
      (AF). This study introduces a novel non-contrast enhanced 3D whole-heart sequence
      providing simultaneous information on the cardiac anatomy-including both the
      arterial and the venous system-(bright-blood volume) and AWT (black-blood
      volume). METHODS: The proposed MT-prepared bright-blood and black-blood phase
      sensitive inversion recovery (PSIR) BOOST framework acquires 2 differently
      weighted bright-blood volumes in an interleaved fashion. The 2 data sets are then
      combined in a PSIR-like reconstruction to obtain a complementary black-blood
      volume for atrial wall visualization. Image-based navigation and non-rigid
      respiratory motion correction are exploited for 100% scan efficiency and
      predictable acquisition time. The proposed approach was evaluated in 11 healthy
      subjects and 4 patients with AF scheduled for RF ablation. RESULTS: Improved
      depiction of the cardiac venous system was obtained in comparison to a T2 
      prepared BOOST implementation, and quantified AWT was shown to be in good
      agreement with previously reported measurements obtained in healthy subjects
      (right atrium AWT: 2.54 +/- 0.87 mm, left atrium AWT: 2.51 +/- 0.61 mm).
      Feasibility for MT-prepared BOOST acquisitions in patients with AF was
      demonstrated. CONCLUSION: The proposed motion-corrected MT-prepared BOOST
      sequence provides simultaneous non-contrast pulmonary vein depiction as well as
      black-blood visualization of atrial walls. The proposed sequence has a large
      spectrum of potential clinical applications and further validation in patients is
      warranted.

PMID- 30230610
TI  - A novel predictive model of outcome in acute myeloid leukemia without favorable
      karyotype based on treatment strategy, karyotype and FLT3-ITD mutational status.

PMID- 30230612
TI  - Lipomatosis of the brachial plexus with associated overgrowth and macrodactyly.

PMID- 30230611
TI  - Low-dose ACTH stimulation testing in dogs suspected of hypoadrenocorticism.
AB  - BACKGROUND: Low-dose ACTH stimulation testing would lower cost and may increase
      sensitivity for identification of partial ACTH deficiency. HYPOTHESIS: (1) The
      low-dose ACTH stimulation test will provide comparable results to the standard
      dose ACTH stimulation test in dogs suspected of hypoadrenocorticism and (2)
      partial ACTH deficiency exists in dogs and can result in chronic, intermittent
      gastrointestinal signs. ANIMALS: Thirty-one client-owned dogs suspected of having
      hypoadrenocorticism. METHODS: Prospective study. Dogs suspected of having
      hypoadrenocorticism received 1 MUg/kg cosyntropin IV for the first ACTH
      stimulation test; the second test was performed 4 h later and dogs received 5
      MUg/kg cosyntropin IV. Blood samples were obtained pre-ACTH and 1 hour post-ACTH
      for each dose (4 measurements total). Samples for endogenous ACTH measurement
      were obtained at the time of initial blood collection. RESULTS: No significant
      difference was observed in the basal cortisol concentration before administration
      of a 1 MUg/kg versus before a 5 MUg/kg dose of cosyntropin (P = .544). For dogs
      suspected of having hypoadrenocorticism, the ACTH-stimulated cortisol
      concentrations in response to both doses of ACTH were equivalent (90% confidence
      interval [CI], 80.5-97.2%; P = .04). No cases with partial ACTH deficiency were
      identified conclusively. CONCLUSIONS AND CLINICAL IMPORTANCE: A 1 MUg/kg dose of
      cosyntropin is equivalent to a 5 MUg/kg dose of cosyntropin for screening dogs
      suspected of hypoadrenocorticism. The existence of partial ACTH deficiency was
      not identified in this small group of dogs.

PMID- 30230613
TI  - Impact of hepatic encephalopathy on liver transplant waiting list mortality in
      regions with different transplantation rates.
AB  - Overt hepatic encephalopathy (OHE) negatively impacts the prognosis of liver
      transplant candidates. However, it is not taken into account in most prioritizing
      organ allocation systems. We aimed to assess the impact of OHE on waitlist
      mortality in 3 cohorts of cirrhotic patients awaiting liver transplantation, with
      differences in the composition of patient population, transplantation policy, and
      transplantation rates. These cohorts were derived from two centers in the
      Netherlands (reference and validation cohort, n = 246 and n = 205, respectively)
      and one in Spain (validation cohort, n = 253). Competing-risk regression analysis
      was applied to assess the association of OHE with 1-year waitlist mortality. OHE
      was found to be associated with mortality, independently of MELD score, other
      cirrhosis-related complications and hepatocellular carcinoma (HCC; sHR = 4.19,
      95% CI = 1.9-9.5, P = 0.001). The addition of extra MELD points for OHE
      counteracted its negative impact on survival. These findings were confirmed in
      the Dutch validation cohort, whereas in the Spanish cohort, containing a
      significantly greater proportion of HCC and with higher transplantation rates,
      OHE was not associated with mortality. In conclusion, OHE is an independent risk
      factor for 1-year waitlist mortality and might be a prioritization rule for organ
      allocation. However, its impact seems to be attenuated in settings with
      significantly higher transplantation rates.

PMID- 30230614
TI  - Molecular Networks in Dynamic Multilevel Systems.
AB  - Dynamic multilevel systems can be assembled from molecular building blocks
      through two or more reversible reactions that form covalent bonds. Molecular
      networks of dynamic multilevel systems can exhibit different connectivities
      between nodes. The design and creation of molecular networks in multilevel
      systems require control of the crossed reactivity of the functional groups (how
      to connect nodes) and the conditions of the reactions (when to connect nodes). In
      recent years, the combination of orthogonal and communicating reactions, which
      can be simultaneous or individually activated, has produced a variety of systems
      that have given rise to macrocycles and cages, as well as molecular motors and
      multicomponent architectures on surfaces. A given set of reactions can lead to
      systems with unique responsiveness, compositions, and functions as a result of
      the relative reactivities. In this Concept article, different molecular networks
      from synthetic systems that can be produced by combinations of different reaction
      types are discussed. Moreover, applications of this chemistry are highlighted,
      and future perspectives are envisioned.

PMID- 30230615
TI  - Reactions of Arylcarbenes with Lewis Acids.
AB  - The reactions of the three triplet ground state arylcarbenes diphenylcarbene 1,
      fluorenylidene 2, and dibenzocycloheptadienylidene 3 with the Lewis acids H2 O,
      ICF3 , and BF3 were studied under the conditions of matrix isolation. H2 O was
      selected as typical hydrogen bond donor, ICF3 as halogen bond donor, and BF3 as
      strong Lewis acid. H2 O forms hydrogen-bonded complexes of the singlet carbenes
      with 1 and 2, but not with 3. This is rationalized by the larger singlet-triplet
      gap of 3, which does not allow to stabilize the singlet state below the triplet
      state by hydrogen bonding. With ICF3 , both 1 and 3 form halogen-bonded complexes
      of the singlet states of the carbenes. This indicates that halogen bonding
      stabilizes singlet carbenes more than hydrogen bonding. Carbene 2 reacts
      differently from 1 and 3 by forming an iodonium ylide, thus avoiding antiaromatic
      destabilization of the fluorenyl unit. With BF3 , all three carbenes form
      zwitterionic Lewis acid/base complexes.

PMID- 30230616
TI  - Chiral recognition of the carnitine enantiomers using rhodamine B as a resonance
      Rayleigh scattering probe.
AB  - A novel and simple method for simultaneous determination of chiral carnitine (CA)
      enantiomers was proposed. In this work, the rhodamine B (RhB) could react with D
      CA and L-CA, and new resonance Rayleigh scattering (RRS) peaks were generated.
      According to the polarization experiments, it could be testified that scattering
      peak of this system was composed of resonance fluorescence and scattering light.
      The RRS intensity of the RhB could be enhanced with the addition of D- or L-CA.
      However, The RRS signal with L-CA had greater degree increased. So a useful assay
      program for the selective and simultaneous determination of CA enantiomers was
      built via the RRS signal differences of the two CA enantiomers responding to RhB.
      The results showing a good linear relationship and high correlation coefficient
      were obtained, and the detection limit was calculated as 0.086 MUg.mL-1 (D-CA)
      and 0.042 MUg.mL-1 (CA). Here, new built RRS method with RhB as chiral probe
      could be applied to achieve selective analysis through this work. The
      applicability of the chiral recognition of CA enantiomers mixtures in samples had
      been demonstrated by its low cost, sensitivity, enantioselectivity, simplicity,
      and good availability of the materials.

PMID- 30230617
TI  - 3D Plate-Lattices: An Emerging Class of Low-Density Metamaterial Exhibiting
      Optimal Isotropic Stiffness.
AB  - In lightweight engineering, there is a constant quest for low-density materials
      featuring high mass-specific stiffness and strength. Additively-manufactured
      metamaterials are particularly promising candidates as the controlled
      introduction of porosity allows for tailoring their density while activating
      strengthening size-effects at the nano- and microstructural level. Here, plate
      lattices are conceived by placing plates along the closest-packed planes of
      crystal structures. Based on theoretical analysis, a general design map is
      developed for elastically isotropic plate-lattices of cubic symmetry. In addition
      to validating the design map, detailed computational analysis reveals that there
      even exist plate-lattice compositions that provide nearly isotropic yield
      strength together with elastic isotropy. The most striking feature of plate
      lattices is that their stiffness and yield strength are within a few percent of
      the theoretical limits for isotropic porous solids. This implies that the
      stiffness of isotropic plate-lattices is up to three times higher than that of
      the stiffest truss-lattices of equal mass. This stiffness advantage is also
      confirmed by experiments on truss- and plate-lattice specimens fabricated through
      direct laser writing. Due to their porous internal structure, the potential
      impact of the new metamaterials reported here goes beyond lightweight
      engineering, including applications for heat-exchange, thermal insulation,
      acoustics, and biomedical engineering.

PMID- 30230618
TI  - Borane-Catalyzed Synthesis of Quinolines Bearing Tetrasubstituted Stereocenters
      by Hydride Abstraction-Induced Electrocyclization.
AB  - The borane-catalyzed synthesis of quinoline derivatives bearing tetrasubstituted
      stereocenters from vinyl anilines has been developed. Mechanistic studies and
      quantum-mechanical investigations support the hydride
      abstraction/electrocyclization/hydride addition mechanism. The products were
      obtained in up to 99 % yield with a diastereoselectivity of >99 % in favour for
      the 3a-5-cis isomer.

PMID- 30230619
TI  - First Micelle-Free Photoredox Catalytic Access to Hydrated Electrons for
      Syntheses and Remediations with a Visible LED or even Sunlight.
AB  - Hydrated electrons are super-reductants, yet can be generated with visible light
      when two photons are pooled, most efficiently through storing the energy of the
      first photon in a radical pair formed by the reduction of an excited catalyst by
      a sacrificial donor. All previous such systems for producing synthetically
      useable amounts of hydrated electrons with an LED in the visible range had to
      resort to compartmentalization by SDS micelles to curb the performance-limiting
      recombination of the pair. To overcome micelle-imposed constraints on
      sustainability and applications, we have instead attached carboxylate groups to a
      ruthenium (tris)bipyridyl catalyst such that its pentaanionic radical strongly
      repels the dianionic radical of the bioavailable donor urate. We have explored
      the influence of the Coulombic interactions on the electron generation by a time
      resolved study from microseconds to hours, including for comparison the
      unsubstituted complex, which forms a monocationic radical, with and without SDS
      micelles. The new homogeneous electron source is best with regard to stability
      and total electron output; it has a broader synthetic scope because it does not
      entail micellar shielding of less hydrophilic compounds, which particularly
      facilitates cross-couplings; and it tolerates supramolecular containers as
      carriers of water-insoluble substrates or products. As an application in the
      field, we demonstrate the solar remediation of a recalcitrant chloro-organic bulk
      chemical.

PMID- 30230620
TI  - Ultraviolet B-induced immunosuppression is not associated with receptor activator
      of nuclear factor kappa B ligand upregulation in human skin.

PMID- 30230621
TI  - Dopamine: Opening the door of movement.

PMID- 30230622
TI  - alpha-Synuclein strains in multiple system atrophy: A product of their
      environment?

PMID- 30230623
TI  - Disease-causing or benign? challenges in genetic variant interpretation and
      limitations of ClinVar.

PMID- 30230625
TI  - Ataxia-telangiectasia: A review of movement disorders, clinical features and
      genotype correlations - Addendum.

PMID- 30230624
TI  - Neurobiology of placebo effect in Parkinson's disease: What we have learned and
      where we are going.
AB  - The placebo effect is a phenomenon produced when an inert substance administered
      like a regular treatment improves the clinical outcome. Parkinson's disease (PD)
      is one of the main clinical disorders for which the placebo response rates are
      high. The first evidence of the neurobiological mechanisms underlying the placebo
      effect in PD stems from 2001, when de la Fuente-Fernandez and colleagues
      demonstrated that a placebo injection led to the release of dopamine in the
      striatal nuclei of PD measured with positron emission tomography technology.
      Since then, several studies have been conducted to investigate the
      neurobiological underpinnings of placebo responses. This article presents a
      systematic review following the Preferred Reporting Items for Systematic Reviews
      and Meta-Analysis guidelines. Of an initial yield of 143 papers, 19 were
      included. The lessons learned from these studies are threefold: (i) motor
      improvement is dependent on the activation of the entire nigrostriatal pathway
      induced by dopamine release in the dorsal striatum; (ii) the magnitude of placebo
      induced effects is modulated by an expectancy of improvement, which is in turn
      related to the release of dopamine within the ventral striatum; (iii) the
      functioning of the neural pathways underlying the placebo response can be tuned
      by prior exposure and learning strategies. In conclusion, although the neural
      network underlying the placebo effect in PD has been largely confirmed and
      accepted, what remains to be established is how, when, and where the expectation
      of reward (mediated by the ventral striatum) interacts with the primary motor
      system (mediated by the dorsal striatum) to induce clinical improvement in motor
      symptoms. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 30230626
TI  - Placebo and nocebo responses in other movement disorders besides Parkinson's
      disease: How much do we know?
AB  - Among movement disorders and medicine in general, PD is one of the conditions for
      which there is a greater knowledge of the placebo and nocebo responses. In other
      movement disorders, the knowledge of placebo and nocebo responses is less. An
      advance in this field is expected to contribute to a better understanding of the
      nature of a therapeutic benefit in clinical research and clinical practice, and
      mechanisms of placebo and nocebo. We conducted a review on placebo and nocebo
      responses in other movement disorders besides PD by primarily examining meta
      analyses of clinical trials assessing specifically the placebo and/or nocebo
      responses. Second, we examined both efficacy and safety results of a placebo arm
      in pivotal placebo-controlled trials for the different movement disorders. RLS is
      the movement disorder for which the most data exist, followed by tic disorders
      and Huntington's disease. Data available in other conditions document a placebo
      response in a varied phenomenology. We found different placebo responses
      according to clinical domains assessed, type of outcomes used for the same
      clinical domain, and modes of treatment administration, including rehabilitation
      and surgical interventions. Data on the nocebo response were very scarce.
      Although the data available are limited, RLS has the better documentation of
      placebo and nocebo responses. In contrast, atypical parkinsonisms are the group
      of movement disorders with the least knowledge. The clinical entities with a more
      robust placebo response are those that have the most beneficial available
      symptomatic treatments. (c) 2018 International Parkinson and Movement Disorder
      Society.

PMID- 30230628
TI  - The placebo response in Parkinson's disease and other movement disorders.

PMID- 30230627
TI  - alpha-Synuclein antibody 5G4 identifies manifest and prodromal Parkinson's
      disease in colonic mucosa.

PMID- 30230630
TI  - Why does the goalkeeper eschew medication? The challenge of new treatments for
      tourette syndrome.

PMID- 30230629
TI  - On the rise: Quantitative measures in Huntington's disease.

PMID- 30230631
TI  - A Facile Synthesis of Ternary Nickel Iron Sulfide Nanospheres as Counter
      Electrode in Dye-Sensitized Solar Cells.
AB  - The incorporation of a foreign metal into a material may adjust the surface
      electronic structure and promote charge transfer, which then ultimately improves
      electrical conductivity and electrocatalytic performance because of the possible
      charge delocalization between the metal cations. As a result, for the first time,
      ternary nickel iron sulfide nanospheres have been successfully fabricated through
      a two-step solvothermal approach with the help of glucose (Ni0.5 Fe0.5 S2 /C).
      Subsequently, the electrochemical performance and electrocatalytic activity of
      Ni0.5 Fe0.5 S2 /C were evaluated by electrochemical impedance spectroscopy, Tafel
      polarization and cyclic voltammetry, indicating high electrical conductivity and
      great electrocatalytic activity. Ni0.5 Fe0.5 S2 /C was employed as a counter
      electrode for dye-sensitized solar cells, and exhibited higher power conversion
      efficiency (6.79 %) than the device with Pt CE (6.31 %) under full sunlight
      illumination (100 mW cm-2 , AM 1.5G).

PMID- 30230632
TI  - FlhF(T368A) modulates motility in the bacteriophage carrier state of
      Campylobacter jejuni.
AB  - The carrier state is an alternative bacteriophage life cycle by which virulent
      bacteriophage can persist in association with host bacteria. Campylobacter jejuni
      carrier state strains exhibit growth phase dependent motility due to a truncated
      flagella phenotype. Genome sequencing identified a T368A substitution in the G3
      domain of the SRP-like GTPase FlhF from C. jejuni PT14CP30A carrier state
      strains, which we hypothesized to be the cause of the complex motility phenotype.
      We have analyzed the role of this mutation in C. jejuni PT14 and demonstrated
      that flhF(T368A) leads to a large proportion of cells unable to synthesize
      flagella, while the remaining cells form a single flagellum at one pole leading
      to significantly reduced motility. The flhF(T368A) mutation causes a reduction in
      the phage adsorption constant, which leads to a decrease in infection efficiency.
      Down-regulation of sigma28 and sigma54 dependent flagellar genes were observed as
      responses to the flhF(T368A) mutation. FlhF(T368A) protein is impaired in GTPase
      activity and exhibits reduced stability. C. jejuni carrying flhF(T368A) are less
      sensitive to bacteriophage infection and formation of the carrier state. The
      acquisition of flhF(T368A) in carrier state strains acts to prevent super
      infection and maintain association with the bacteriophage that provoked the
      interaction.

PMID- 30230633
TI  - Fluoroalkyl radical generation by homolytic bond dissociation in
      pentacarbonylmanganese derivatives.
AB  - Thermal decarbonylation of the acyl compounds [Mn(CO)5(CORF)] (RF = CF3, 1; CHF2,
      2; CH2CF3, 3; CF2CH3, 4) yields the corresponding alkyl derivatives [Mn(CO)5(RF)]
      (RF = CF3, 5; CHF2, 6; CH2CF3, 7; CF2CH3, 8). Compounds 3, 4, 7 and 8 have not
      been previously reported. All compounds, except 8 which could not be obtained in
      a pure state, were fully characterized by analytical and spectroscopic methods,
      as well as by single-crystal X-ray diffraction for 1, 2, 4, 5, 6 and 7. The
      solution IR characterization in the CO stretching region, with the assistance of
      DFT calculations, has allowed the assignment of several weak bands to vibrations
      of the [Mn(12CO)4(eq-13CO)(RF)] and [Mn(12CO)4(ax-13CO)(RF)] isotopomers and a
      ranking of the RF donor power in the order CF3 < CHF2 < CH2CF3 ~ CF2CH3. The
      homolytic Mn-RF bond cleavage in [Mn(CO)5(RF)], carried out at various
      temperatures for compounds 5, 6 and 7 under saturation conditions, with trapping
      of the generated RF radicals by tris(trimethylsilyl)silane (TTMSS, 10 equiv), has
      yielded activation parameters DeltaH? and DeltaS? that are believed to represent
      close estimates of the homolytic bond dissociation thermodynamic parameters. The
      values (DeltaH? = 53.8 +/- 3.5 (5), 46.3+/-1.6 (6), 50.6+/-0.8 (7) kcal/mol;
      DeltaS? = 66.0+/-9.5 (5), 55.8+/-4.7 (6), 65.4+/-2.2 (7) cal mol-1 K-1) are in
      close agreement with the results of a recent DFT study (J. Organomet. Chem. 2018,
      864, 12-18).

PMID- 30230634
TI  - Enantioselective Bromolactonization of Trisubstituted Olefinic Acids Catalyzed by
      Chiral Pyridyl Phosphoramides.
AB  - Enantioselective bromolactonization of trisubstituted olefinic acids producing
      synthetically useful chiral lactones with two contiguous asymmetric centers has
      remained mainly unexplored except for the 6-exo cyclization mode. In this work,
      the 5-exo- and 6-endo modes of bromocyclization of trisubstituted olefinic acids
      were enabled for the first time using N-bromosuccinimide and a pyridyl
      phosphoramide catalyst. The utility of the resulting bromolactones was
      demonstrated by transformations harnessing reactive alkyl bromide moieties
      without losing stereochemical information. Optimization studies and control
      experiments revealed that the basicity of pyridine moieties and presence of N-H
      protons in the phosphoramide species strongly affected both the reactivity and
      enantioselectivity parameters.

PMID- 30230635
TI  - Optimal repetition time reduction for single subject event-related functional
      magnetic resonance imaging.
AB  - PURPOSE: Short TRs are increasingly used for fMRI as fast sequences such as
      simultaneous multislice excitation become available. These have been associated
      with apparent sensitivity improvements, although greater temporal autocorrelation
      at shorter TRs can inflate sensitivity measurements leading to uncertainty
      regarding the optimal approach. METHODS: In volunteers (n = 10), the optimal TR
      was assessed at the single subject level for event-related designs (visual
      stimulation) with 4 frequencies of presentation at 4 TR values (412-2550 ms). T
      values in the visual cortex localized in each individual were obtained and
      receiver operating characteristics (ROC) analysis was performed by counting
      voxels within and outside expected task active regions at different thresholds.
      This analysis was repeated using 4 different autoregressive (AR) models; SPM
      AR(1) and SPM AR(fast) which globally estimate autocorrelation, and fMRIstat
      AR(1) and AR(5) that use a local estimate. RESULTS: The use of modest multiband
      factors of 2 or 3 with a reduction in TR to 1000 +/- 200 ms had greater
      sensitivity and specificity as shown by higher T-values in visual cortex and ROC
      analysis. At these TRs, the ROC analysis demonstrated that a local AR model fit
      improved performance while high order AR models were unnecessary. CONCLUSIONS:
      Modest TR reductions (to 1000 +/- 200 ms) optimally improved event-related fMRI
      performance independent of design frequency. Autoregressive models with a local
      as opposed to global fit performed better, while low order autoregressive models
      were sufficient at the optimal TR.

PMID- 30230636
TI  - A Solanum neorickii introgression population providing a powerful complement to
      the extensively characterized Solanum pennellii population.
AB  - We present a complementary resource for trait fine-mapping in tomato to those
      based on the intra-specific cross between cultivated tomato and the wild tomato
      species Solanum pennellii, which have been extensively used for quantitative
      genetics in tomato over the last 20 years. The current population of backcross
      inbred lines (BILs) is composed of 107 lines derived after three backcrosses of
      progeny of the wild species Solanum neorickii (LA2133) and cultivated tomato
      (cultivar TA209) and is freely available to the scientific community. These S.
      neorickii BILs were genotyped using the 10K SolCAP single nucleotide polymorphism
      chip, and 3111 polymorphic markers were used to map recombination break points
      relative to the physical map of Solanum lycopersicum. The BILs harbor on average
      4.3 introgressions per line, with a mean introgression length of 34.7 Mbp,
      allowing partitioning of the genome into 340 bins and thereby facilitating rapid
      trait mapping. We demonstrate the power of using this resource in comparison with
      archival data from the S. pennellii resources by carrying out metabolic
      quantitative trait locus analysis following gas chromatography-mass spectrometry
      on fruits harvested from the S. neorickii BILs. The metabolic candidate genes
      phenylalanine ammonia-lyase and cystathionine gamma-lyase were then tested and
      validated in F2 populations and via agroinfiltration-based overexpression in
      order to exemplify the fidelity of this method in identifying the genes that
      drive tomato metabolic phenotypes.

PMID- 30230637
TI  - Effective antimicrobial activity of rifabutin against multidrug-resistant
      Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori resistance to more than one antibiotic is the
      main reason for failure in bacterial eradication in a considerable number of
      patients. Rifabutin (RFB) with a broad-spectrum of antimicrobial therapy has been
      suggested for treatment of refractory multidrug-resistant infections. METHODS:
      Helicobacter pylori isolates from 104 patients were examined for resistance to 5
      currently used antibiotics and RFB, using agar dilution method. Twofold serial
      dilutions of antibiotics were used and MICs (MUg/mL) determined as metronidazole
      (MTZ 8), clarithromycin (CLR 2), amoxicillin (AMX 1), tetracycline (TET 0.5),
      furazolidone (FRZ 0.5), and RFB (0.06). RESULTS: Of 104 H. pylori isolates, only
      7 (6.7%) were sensitive to all the 6 antibiotics. However, 30 (28.8%) were
      resistant to one antibiotic, 28 (26.9%) to two, 19 (18.2%) to three, 14 (13.4%)
      to four, and 6 (5.7%) to five currently used antibiotics. Overall, 67(64.4%) of
      isolates were resistant to 2-5 currently used antibiotics and considered as
      multidrug-resistant (MDR), with 59 (88.1%) showing sensitivity to RFB and 8
      (11.9%) resistance (P < 0.05). Of 33 isolates resistant to both MTZ and CLR, 25
      (75.7%) were sensitive to RFB and 8 (24.3%) resistant (P < 0.05). DISCUSSION: In
      vitro antimicrobial effectiveness of RFB on MDR H. pylori including those with
      resistance to both MTZ and CLR was demonstrated. However, RFB efficacy decreased
      as the number of antibiotics responsible for MDR increased. Considering that RFB
      inhibits both extra- and intracellular H. pylori, it can be suggested as an
      effective antibiotic against of MDR H. pylori.

PMID- 30230638
TI  - Multicenter Measurements of T1 Relaxation and Diffusion Tensor Imaging: Intra and
      Intersite Reproducibility.
AB  - BACKGROUND AND PURPOSE: Quantitative T1 and diffusion tensor imaging (DTI) may
      provide information about pathological changes underlying disability and
      progression in diseases like multiple sclerosis (MS). Imaging the corpus callosum
      (CC), a primary site of damage in MS with a critical role in interhemispheric
      connectivity, may be useful for assessing overall brain health, prognosis, and
      therapy efficacy. We assessed the feasibility of multisite clinical trials using
      advanced MRI by examining the intra and intersite reproducibility of T1 and DTI
      measurements in the CC and segmented white matter (WM). METHODS: Five healthy
      volunteers were scanned twice within 24 hours at six 3T sites. Coefficients of
      variation (COVs) and intraclass correlation coefficients (ICCs) for CC and WM T1
      , fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Dax ),
      and radial diffusivity (Drad ) assessed intrasite and intersite reliability.
      RESULTS: CC and WM T1 showed excellent intrasite reproducibility with low COVs
      (mean = .90% and .89%, respectively) and good ICCs (CC = .78, WM = .90). T1 also
      demonstrated intersite reliability (low COVs: CC = 2.4%, WM = 1.8%; moderate
      ICCs: CC = .43, WM = .69). DTI had low intrasite COVs (CC: FA = 1.3%, MD = 1.5%,
      Dax = 1.4%, Drad = 2.2%; WM: FA = .9%, MD = .9%, Dax = .7%, Drad = 1.2%) and high
      intrasite ICCs (CC: FA = .95, MD = .97, Dax = .94, Drad = .97; CC: FA = .9, MD =
      .66, Dax = .88, Drad = .63), indicating excellent intrasite reproducibility. DTI
      also showed excellent intersite reliability with low COVs (CC: FA = 2.1%, MD =
      4.1%, Dax = 3.4%, Drad = 5.3%, WM: FA = 1.3%, MD = 1.9%, Dax = 1.8%, Drad =
      2.1%,) and good ICCs (CC: FA = .90, MD = .84, Dax = .72, Drad = .90; WM: FA =
      .83, MD = .34, Dax = .62, Drad = .41). CONCLUSIONS: T1 and DTI measures are
      reproducible using equivalent MRI scanners and sequence protocols. Using a
      similar MR system, it is feasible to carry out multicenter studies using T1 and
      DTI to evaluate changes within the CC and WM.

PMID- 30230639
TI  - Rare-Earth Cyclobutadienyl Sandwich Complexes: Synthesis, Structure and Dynamic
      Magnetic Properties.
AB  - The potassium cyclobutadienyl [K2 {eta4 -C4 (SiMe3 )4 }] (1) reacts with MCl3
      (THF)3.5 (M=Y, Dy) to give the first rare-earth cyclobutadienyl complexes, that
      is, the complex anions [M{eta4 -C4 (SiMe3 )4 }{eta4 -C4 (SiMe3 )3 -kappa-(CH2
      SiMe2 }]2- , (2M ), as their dipotassium salts. The tuck-in alkyl ligand in 2M is
      thought to form through deprotonation of the "squarocene" complexes [M{eta4 -C4
      (SiMe3 )4 }2 ]- by 1. Complex 2Dy is a single-molecule magnet, but with prominent
      quantum tunneling. An anisotropy barrier of 323(22) cm-1 was determined for 2Dy
      in an applied field of 1 kOe, and magnetic hysteresis loops were observed up to 7
      K.

PMID- 30230640
TI  - Peptide-based multi-agonists: a new paradigm in metabolic pharmacology.
AB  - Obesity and its comorbidities, such as type 2 diabetes, are pressing worldwide
      health concerns. Available anti-obesity treatments include weight loss
      pharmacotherapies and bariatric surgery. Whilst surgical interventions typically
      result in significant and sustained weight loss, available pharmacotherapies are
      far less effective, typically decreasing body weight by no more than 5-10%. An
      emerging class of multi-agonist drugs may eventually bridge this gap. This new
      class of specially tailored drugs hybridizes the amino acid sequences of key
      metabolic hormones into one single entity with enhanced potency and sustained
      action. Successful examples of this strategy include multi-agonist drugs
      targeting the receptors for glucagon-like peptide-1 (GLP-1), glucagon and the
      glucose-dependent insulinotropic polypeptide (GIP). Due to the simultaneous
      activity at several metabolically relevant receptors, these multi-agonists offer
      improved body weight loss and glucose tolerance relative to their constituent
      monotherapies. Further advancing this concept, chimeras were generated that
      covalently link nuclear acting hormones such as oestrogen, thyroid hormone (T3 )
      or dexamethasone to peptide hormones such as GLP-1 or glucagon. The benefit of
      this strategy is to restrict the nuclear hormone action exclusively to cells
      expressing the peptide hormone receptor, thereby maximizing combinatorial
      metabolic efficacy of both drug constituents in the target cells whilst
      preventing the nuclear hormone cargo from entering and acting on cells devoid of
      the peptide hormone receptor, in which the nuclear hormone might have unwanted
      effects. Many of these multi-agonists are in preclinical and clinical development
      and may represent new and effective tools in the fight against obesity and its
      comorbidities.

PMID- 30230641
TI  - High-dose vitamin D: Without benefit but not without risk.

PMID- 30230642
TI  - Catalytic diversity and cell wall binding repeats in the phage-encoded
      endolysins.
AB  - Bacteriophage-encoded endolysins can recognize and bind specific bacteria, and
      act to cleave the glycosidic and/or amide bonds in the peptidoglycan (PG)
      bacterial cell wall. Cleavage of the cell wall generally results in the death of
      the bacteria. Their utility as bacteriolytic agents could be exploited for human
      and veterinary medicines as well as various biotechnological applications. As
      interest grows in the commercial uses of these proteins, there has been much
      effort to successfully employ rational design and engineering to produce
      endolysins with bespoke properties. In this review, we interrogate the current
      structural data and identify structural features that would be of benefit to
      engineering the activity and specificity of phage endolysins. We show that the
      growing body of structural data can be used to predict catalytic residues and
      mechanism of action from sequences of hypothetical endolysins, and probe the
      importance of secondary structure repeats in bacterial cell wall-binding domains.

PMID- 30230643
TI  - Genomic features of the Helicobacter pylori strain PMSS1 and its virulence
      attributes as deduced from its in vivo colonisation patterns.
AB  - The human gastric pathogen Helicobacter pylori occurs in two basic variants,
      either exhibiting a functional cagPAI-encoded type-4-secretion-system (T4SS) or
      not. Only a few cagPAI-positive strains have been successfully adapted for long
      term infection of mice, including the pre-mouse Sydney strain 1 (PMSS1). Here we
      confirm that PMSS1 induces gastric inflammation and neutrophil infiltration in
      mice, progressing to intestinal metaplasia. Complete genome analysis of PMSS1
      revealed 1,423 coding sequences, encompassing the cagPAI gene cluster and,
      unusually, the location of the cytotoxin-associated gene A (cagA) approximately
      15 kb downstream of the island. PMSS1 harbours three genetically exchangeable
      loci that are occupied by the hopQ coding sequences. HopQ represents a critical
      co-factor required for the translocation of CagA into the host cell and
      activation of NF-kappaB via the T4SS. Long-term colonisation of mice led to an
      impairment of cagPAI functionality. One of the bacterial clones re-isolated at
      four months post-infection revealed a mutation in the cagPAI gene cagW, resulting
      in a frame shift mutation, which prevented CagA translocation, possibly due to an
      impairment of T4SS function. Rescue of the mutant cagW re-established CagA
      translocation. Our data reveal intriguing insights into the adaptive abilities of
      PMSS1, suggesting functional modulation of the H. pylori cagPAI virulence
      attribute.

PMID- 30230644
TI  - Wheat grain protein accumulation and polymerization mechanisms driven by nitrogen
      fertilization.
AB  - In wheat (Triticum aestivum) grain yield and grain protein content are negatively
      correlated, making the simultaneous increase of the two traits challenging. Apart
      from genetic approaches, modification of nitrogen fertilization offers a feasible
      option to achieve this aim. In this study, a range of traits related to nitrogen
      use efficiency in six Australian bread wheat varieties were investigated under
      different nitrogen treatments using 3-year multisite field trials. Changes in the
      individual storage protein composition were detected by high-performance liquid
      chromatography. Our results indicated that wheat grain yield and grain protein
      content reacted similarly to nitrogen availability, with grain yield being
      slightly more sensitive than grain protein content, and that genotype is a vital
      determinant of grain protein yield. Measurement of the glutamine synthetase
      activity of flag leaves and developing grains revealed that high nitrogen
      availability prompted the participation of glutamine in biological processes. In
      addition, a more significant accumulation of gluten macropolymer was observed
      under the high-nitrogen treatment from 21 days post-anthesis, and the underlying
      mechanism was elucidated by a comparative proteomics study. A yeast two-hybrid
      experiment confirmed this mechanism. The results of this study revealed that
      peptidyl-prolyl cis-trans isomerase (PPIase) was SUMOylated with the assistance
      of small ubiquitin-related modifier 1 and that high nitrogen availability
      facilitated this connection for the subsequent protein polymerization.
      Additionally, luminal-binding protein 2 in the endoplasmic reticulum played a
      similar role to PPIase in the aggregation of protein under high-nitrogen
      conditions.

PMID- 30230645
TI  - Striatal cholinergic interneurons regulate cognitive and affective dysfunction in
      partially dopamine-depleted mice.
AB  - Early non-motor symptoms such as mood disorders and cognitive deficits are
      increasingly recognised in Parkinson's disease (PD). They may precede the
      characteristic motor symptomatology caused by dopamine (DA) neuronal loss in the
      substantia nigra pars compacta (SNc). It is well known that striatal cholinergic
      interneurons (ChIs) are emerging as key regulators of PD motor symptom, however,
      their involvement in the cognitive and affective alterations occurring in the
      premotor phase of PD is poorly understood. We used optogenetic photoinhibition of
      striatal ChIs in mice with mild nigrostriatal 6-hydroxydopamine (6-OHDA) lesions
      and assessed their role in anxiety-like behaviour in the elevated plus maze,
      social memory recognition of a congener and visuospatial object recognition. In
      transgenic mice specifically expressing halorhodopsin (eNpHR) in cholinergic
      neurons, striatal ChIs photoinhibition reduced the anxiety-like behaviour and
      reversed social and spatial short-term memory impairment induced by moderate DA
      depletion (e.g., 50% loss of tyrosine hydroxylase TH-positive neurons in the
      SNc). Systemic injection of telenzepine (0.3 mg/kg), a preferential M1 muscarinic
      cholinergic receptors antagonist, improved anxiety-like behaviour, social memory
      recognition but not spatial memory deficits. Our results suggest that dysfunction
      of the striatal cholinergic system may play a role in the short-term cognitive
      and emotional deficits of partially DA-depleted mice. Blocking cholinergic
      activity with M1 muscarinic receptor antagonists may represent a possible
      therapeutic target, although not exclusive, to modulate these early non-motor
      deficits.

PMID- 30230647
TI  - Influence of ultrasonic activation using different final irrigants on
      antimicrobial activity, smear layer removal and bond strength of filling
      material.
AB  - The aim of this study was to evaluate the influence of ultrasonic activation (US)
      over final irrigants on antimicrobial activity, smear layer removal and bond
      strength. The root canals of 180 extracted human teeth were distributed into
      three experimental tests (n = 60). In each test, the samples were subdivided into
      six groups (n = 10) according to final irrigation protocols: G1:distilled water
      (DW); G2:DW + US; G3:17% EDTA; G4:QMix; G5:17% EDTA + US; and G6:QMix + US. The
      antimicrobial activity was evaluated by counting of colony-forming units (CFUs),
      the smear layer removal by scanning electron microscopy and the bond strength by
      push-out test. Statistical analysis was performed for each evaluation (alpha =
      5%). Groups 4 and 6 provided higher bacterial reduction, groups 5 and 6 provided
      higher smear layer removal, groups 3, 4, 5 and 6 provided the higher bond
      strength (P < 0.05). US activation did not improve the antimicrobial activity and
      the bond strength, whereas it improved the smear layer removal.

PMID- 30230646
TI  - Investigation of analysis methods for hyperpolarized 13C-pyruvate metabolic MRI
      in prostate cancer patients.
AB  - MRI using hyperpolarized (HP) carbon-13 pyruvate is being investigated in
      clinical trials to provide non-invasive measurements of metabolism for cancer and
      cardiac imaging. In this project, we applied HP [1-13 C]pyruvate dynamic MRI in
      prostate cancer to measure the conversion from pyruvate to lactate, which is
      expected to increase in aggressive cancers. The goal of this work was to develop
      and test analysis methods for improved quantification of this metabolic
      conversion. In this work, we compared specialized kinetic modeling methods to
      estimate the pyruvate-to-lactate conversion rate, kPL , as well as the lactate-to
      pyruvate area-under-curve (AUC) ratio. The kinetic modeling included an
      "inputless" method requiring no assumptions regarding the input function, as well
      as a method incorporating bolus characteristics in the fitting. These were first
      evaluated with simulated data designed to match human prostate data, where we
      examined the expected sensitivity of metabolism quantification to variations in
      kPL , signal-to-noise ratio (SNR), bolus characteristics, relaxation rates, and
      B1 variability. They were then applied to 17 prostate cancer patient datasets.
      The simulations indicated that the inputless method with fixed relaxation rates
      provided high expected accuracy with no sensitivity to bolus characteristics. The
      AUC ratio showed an undesired strong sensitivity to bolus variations. Fitting the
      input function as well did not improve accuracy over the inputless method. In
      vivo results showed qualitatively accurate kPL maps with inputless fitting. The
      AUC ratio was sensitive to bolus delivery variations. Fitting with the input
      function showed high variability in parameter maps. Overall, we found the
      inputless kPL fitting method to be a simple, robust approach for quantification
      of metabolic conversion following HP [1-13 C]pyruvate injection in human prostate
      cancer studies. This study also provided initial ranges of HP [1-13 C]pyruvate
      parameters (SNR, kPL , bolus characteristics) in the human prostate.

PMID- 30230648
TI  - Cell cycle-dependent regulation of FtsZ in Escherichia coli in slow growth
      conditions.
AB  - FtsZ is the key regulator of bacterial cell division. It initiates division by
      forming a dynamic ring-like structure, the Z-ring, at the mid-cell. What triggers
      the formation of the Z-ring during the cell cycle is poorly understood. In
      Escherichia coli, the common view is that FtsZ concentration is constant
      throughout its doubling time and therefore regulation of assembly is controlled
      by some yet-to-be-identified protein-protein interactions. Using a newly
      developed functional, fluorescent FtsZ reporter, we performed a quantitative
      analysis of the FtsZ concentration throughout the cell cycle under slow growth
      conditions. In contrast to the common expectation, we show that FtsZ
      concentrations vary in a cell cycle-dependent manner, and that upregulation of
      FtsZ synthesis correlates with the formation of the Z-ring. The first half of the
      cell cycle shows an approximately fourfold upregulation of FtsZ synthesis,
      followed by its rapid degradation by ClpXP protease in the last 10% of the cell
      cycle. The initiation of rapid degradation coincides with the dissociation of
      FtsZ from the septum. Altogether, our data suggest that the Z-ring formation in
      slow growth conditions in E. coli is partially controlled by a regulatory
      sequence wherein upregulation of an essential cell cycle factor is followed by
      its degradation.

PMID- 30230650
TI  - Annual decline in arterial blood oxygen predicts development of chronic
      respiratory failure in COPD with mild hypoxaemia: A 6-year follow-up study.
AB  - BACKGROUND AND OBJECTIVE: Chronic respiratory failure (CRF) with hypoxaemia is an
      important pathophysiology in patients with chronic obstructive pulmonary disease
      (COPD), and existing mild hypoxaemia may be a sign of future CRF development.
      However, little is known about the trajectory of partial arterial pressure of
      oxygen (PaO2 ) decline in patients with COPD. We assessed decline in PaO2 and the
      impact of short-term reductions in PaO2 to predict future decline in PaO2 .
      METHODS: A total of 172 outpatients with COPD from a prospective cohort study
      were enrolled. Pulmonary function tests and arterial blood gas (ABG) analyses
      were conducted at baseline and 1 year after enrolment and changes in PaO2
      (DeltaPaO2 ) and other parameters were calculated. Survival and incidence of CRF
      (as assessed by prescription of long-term home oxygen therapy) were monitored for
      6 years. RESULTS: A total of 164 patients completed the observation period and
      101 patients had mild hypoxaemia (PaO2  < 80 Torr) at baseline. No patients with
      normal PaO2 (>=80 Torr) developed CRF, and 10 patients with mild hypoxaemia
      developed CRF in 6 years. Baseline airflow limitation and diffusion capacity were
      significantly associated with development of CRF. Receiver-operating
      characteristic curve analysis showed that DeltaPaO2 of -3.05 Torr/year is a
      useful cut-off value to predict development of CRF in 6 years (hazard ratio (HR):
      12.6, 95% CI: 3.48-58.73, P < 0.0001). CONCLUSION: Patients with COPD and mild
      hypoxaemia may benefit from repeat ABG after 1 year. Although PaO2 trajectories
      widely varied, significant annual changes in PaO2 of at least -3.0 Torr/year were
      predictive of CRF development.

PMID- 30230649
TI  - Association of antithyroglobulin antibodies with the development of thyroid
      dysfunction induced by nivolumab.
AB  - Thyroid dysfunction (TD) induced by immune checkpoint inhibitors is not
      sufficiently understood. The purpose of this retrospective observational study
      was to identify risk factors and the clinical course of TD induced by nivolumab.
      Patients with advanced solid tumors who were treated with nivolumab from March
      2009 through to March 2016 at the National Cancer Center Hospital (Tokyo, Japan)
      were included. Thyroid function and antithyroid Abs from serum samples among all
      patients were evaluated at baseline and during nivolumab treatment. Overt
      hypothyroidism was defined as low serum-free T4 together with elevated thyroid
      stimulating hormone (TSH) >10 MUIU/mL. Thyrotoxicosis was defined as low TSH with
      elevated free T4 and/or free T3. We defined thyroid autoimmunity as the presence
      of antithyroid Abs at baseline, including antithyroid peroxidase Abs and
      antithyroglobulin Abs (TgAb). Twenty-three (14%) of a total of 168 patients
      developed TD, including 17 cases of hypothyroidism and 20 of thyrotoxicosis.
      Thyrotoxicosis followed by hypothyroidism occurred in 14 cases. Fourteen of 35
      patients (40%) with thyroid autoimmunity developed TD vs 9 of 133 (7%) without
      (odds ratio 9.19; 95% confidence interval [CI], 3.53-23.9). In multivariate
      analysis, elevated TSH and TgAb at baseline were significantly associated with
      the development of TD, with odds ratio of 7.36 (95% CI, 1.66-32.7) and 26.5 (95%
      CI, 8.18-85.8), respectively. Association between TD and elevated antithyroid
      peroxidase Abs at baseline was not significant. These results suggest that
      patients with pre-existing TgAb and elevated TSH at baseline are at high risk of
      TD.

PMID- 30230651
TI  - Designing Eco-Sustainable Dye-Sensitized Solar Cells by the Use of a Menthol
      Based Hydrophobic Eutectic Solvent as an Effective Electrolyte Medium.
AB  - The use of a hydrophobic eutectic solvent based on dl-menthol and a naturally
      occurring acid such as acetic acid has been tested as an eco-friendly electrolyte
      medium in dye-sensitized solar cells. In the presence of a de-aggregating agent
      and a representative hydrophobic organic photosensitizer, the corresponding
      devices displayed relatively good power conversion efficiencies in very thin
      active layers. In particular, the higher cell photovoltage detected in comparison
      to devices based on toxic and volatile organic compounds may stem from a more
      efficient interface interaction, as suggested by electrochemical impedance
      spectroscopy studies showing greater charge recombination resistance and electron
      lifetime.

PMID- 30230652
TI  - Active site flexibility revealed in crystal structures of Parabacteroides merdae
      beta-glucuronidase from the human gut microbiome.
AB  - beta-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in
      maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy
      and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop
      2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database.
      Here, we report the crystal structure of P. merdae GUS and highlight the
      differences between this enzyme and extant structures of gut microbial GUS
      proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary
      structure and that the mL2 motif traces a unique path within the active site,
      which also includes two arginines distinctive to this GUS. We observe two states
      of the P. merdae GUS active site; a loop repositions itself by more than 50 A to
      place a functionally-relevant residue into the enzyme's catalytic site. Finally,
      we find that P. merdae GUS is able to bind to homo and heteropolymers of the
      polysaccharide alginic acid. Together, these data broaden our understanding of
      the structural and functional diversity in the GUS family of enzymes present in
      the human gut microbiome and point to specialization as an important feature of
      microbial GUS orthologs.

PMID- 30230654
TI  - Insight into the Mechanochemical Synthesis and Structural Evolution of Hybrid
      Organic-Inorganic Guanidinium Lead(II) Iodides.
AB  - The in situ investigations of the mechanochemical synthesis of four hybrid
      organic-inorganic lead(II) iodides with the formula (C(NH2 )3 )n PbI2+n (n=1, 2,
      3, and 4) are presented. Synchrotron X-ray diffraction data show that the four
      guanidinium lead(II) iodides easily convert into each other. Although the end
      product is dictated by the initial stoichiometry, complex pathways were found
      with different behaviors of the compounds in terms of nucleation, growth, and
      intermediate formation. This appears to be linked to the respective structural
      features of the different compounds, especially the connectivity of the inorganic
      framework and the strength of ionic interactions. High-temperature studies were
      conducted on compounds 1, 3, and 4 to reveal the new phases 1-II, 3-II, and 3
      III. Unknown structures were solved from single-crystal analysis and powder X-ray
      diffraction.

PMID- 30230655
TI  - Triaging treatable traits in asthma.

PMID- 30230656
TI  - Family impact of childhood neurodevelopmental disability: considering adaptive
      and maladaptive behaviour.
AB  - BACKGROUND: The aim of the current study was to identify functional predictors of
      perceived impact of childhood disability among families of children with
      neurodevelopmental disorders and disabilities. We first examined the relationship
      between sub-domains of adaptive and problematic behaviour and perceived family
      impact. Second, we examined whether the same sub-domains would emerge as
      significant after controlling for the impact of child diagnosis, including autism
      spectrum disorder, cerebral palsy and intellectual disability. METHOD: Caregivers
      of 216 children and adolescents (M = 8.17 years) with neurodevelopmental disorder
      and disability completed measures of children's practical, conceptual and social
      skills (i.e. adaptive behaviour), behaviour problems and positive and negative
      family impact. RESULTS: Indices of child adaptive and problematic behaviour were
      only significantly associated with perceived negative family impact. Children's
      practical and social skills, as well as emotional symptoms, emerged as
      significant predictors of perceived negative family impact, with emotional
      symptoms accounting for greatest variance. Including diagnosis in our statistical
      models did not explain additional variance above and beyond these particular sub
      domains of child functioning. CONCLUSIONS: The study findings suggest that it is
      not children's most impaired domains of functioning that are perceived as
      significantly impactful by the family. The findings highlight the importance of
      devoting consideration to the ways in which the functional limitations
      experienced by children with chronic developmental health conditions similarly
      impact family life and well-being, regardless of disorder designation.

PMID- 30230653
TI  - Optimizing poly (ADP-ribose) polymerase inhibition through combined epigenetic
      and immunotherapy.
AB  - Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with
      poor survival outcomes. Currently, there are no targeted therapies available for
      TNBCs despite remarkable progress in targeted and immune-directed therapies for
      other solid organ malignancies. Poly (ADP-ribose) polymerase inhibitors (PARPi)
      are effective anticancer drugs that produce good initial clinical responses,
      especially in homologous recombination DNA repair-deficient cancers. However,
      resistance is the rule rather than the exception, and recurrent tumors tend to
      have an aggressive phenotype associated with poor survival. Many efforts have
      been made to overcome PARPi resistance, mostly by targeting genes and effector
      proteins participating in homologous recombination that are overexpressed during
      PARPi therapy. Due to many known and unknown compensatory pathways, genes, and
      effector proteins, overlap and shared resistance are common. Overexpression of
      programmed cell death-ligand 1 (PD-L1) and cancer stem cell (CSC) sparing are
      novel PARPi resistance hypotheses. Although adding programmed cell death-1 (PD
      1)/PD-L1 inhibitors to PARPi might improve immunogenic cell death and be crucial
      for durable responses, they are less likely to target the CSC population that
      drives recurrent tumor growth. Lysine-specific histone demethylase-1A and histone
      deacetylase inhibitors have shown promising activity against CSCs. Combining
      epigenetic drugs such as lysine-specific histone demethylase-1A inhibitors or
      histone deacetylase inhibitors with PARPi/anti-PD-1/PD-L1 is a novel, potentially
      synergistic strategy for priming tumors and overcoming resistance. Furthermore,
      such an approach could pave the way for the identification of new upstream
      epigenetic and genetic signatures.

PMID- 30230657
TI  - Ruthenium Complexes Bearing Thiophene-Based Unsymmetrical N-Heterocyclic Carbene
      Ligands as Selective Catalysts for Olefin Metathesis in Toluene and
      Environmentally Friendly 2-Methyltetrahydrofuran.
AB  - Three mono-N-heterocyclic carbene (NHC) ruthenium 2-isopropoxybenzylidene (10 a
      c) and one bis(NHC) indenylidene complex (8) bearing an unsymmetrical N
      heterocyclic carbene ligand were synthesized and structurally characterized by
      single-crystal X-ray diffraction. The catalytic activity of the newly obtained
      complexes were evaluated in ring-closing metathesis (RCM) and ene-yne (RCEYM)
      reactions in toluene and environmentally friendly 2-MeTHF under air. The results
      confirmed that although all tested reactions can be successfully mediated by
      catalysts 10 a-c, their general reactivity is lower than the benchmark all
      purpose Ru catalysts with symmetrical NHC ligands. However, the latter cannot
      compete with specialized ruthenium complex 10 a in industrially relevant self-CM
      of terminal olefins in neat conditions.

PMID- 30230659
TI  - Melbourne epidemic thunderstorm asthma event 2016: Lessons learnt from the
      perfect storm.

PMID- 30230658
TI  - Enhancing the language development of toddlers in foster care by promoting foster
      parents' sensitivity: Results from a randomized controlled trial.
AB  - : Young children in foster care are at increased risk for problematic language
      development, making early intervention a critical tool in enhancing these
      children's foundational language abilities. This study examined the efficacy of
      an early preventative intervention, Attachment and Biobehavioral Catch-up for
      Toddlers (ABC-T), in improving the receptive vocabulary abilities of toddlers
      placed in foster care. All the children had been removed from their biological
      parents' care and placed into foster care. When children were between 24 and 36
      months old, foster parents were contacted by research staff and consented to
      participate. Parents were randomly assigned using a random number generator to
      receive either ABC-T (n = 45), which aimed to promote sensitive parenting for
      children who have experienced early adversity, or a control intervention (n =
      43). Foster children's receptive vocabulary skills were assessed post
      intervention using the Peabody Picture Vocabulary Test, Third Edition, when
      children were between 36 and 60 months old. Children whose foster parents
      received ABC-T demonstrated more advanced receptive vocabulary abilities than
      children whose foster parents received the control intervention. The positive
      effect of ABC-T on foster children's receptive vocabulary was mediated by
      increases in foster parents' sensitivity during parent-child interactions. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01261806.

PMID- 30230660
TI  - Declining glacier cover threatens the biodiversity of alpine river diatom
      assemblages.
AB  - Climate change poses a considerable threat to the biodiversity of high altitude
      ecosystems worldwide, including cold-water river systems that are responding
      rapidly to a shrinking cryosphere. Most recent research has demonstrated the
      severe vulnerability of river invertebrates to glacier retreat but effects upon
      other aquatic groups remain poorly quantified. Using new data sets from the
      European Alps, we show significant responses to declining glacier cover for
      diatoms, which play a critical functional role as freshwater primary producers.
      Specifically, diatom alpha-diversity and density in rivers presently fed by
      glaciers will increase with future deglaciation, yet beta-diversity within and
      between sites will reduce because declining glacier influence will lower the
      spatiotemporal variability of glacier cover and its associated habitat
      heterogeneity. Changes in diatom assemblage composition as glacier cover declined
      were associated strongly with increasing riverbed stability and water
      temperature. At the species level, diatoms showed a gradation of responses; for
      example, Eunotia trinacria, found exclusively at river sites with high (>=52%)
      catchment glacier cover, may be affected negatively by ice loss. Conversely,
      seven taxa confined to sites with no glacier cover, including Gomphonema
      calcareum, stand to benefit. Nineteen (22%) taxa were noted as threatened,
      endangered, rare or decreasing on the Red List of Algae for Germany, with most at
      sites <=26% glacier cover, meaning further ice loss may benefit these diatoms.
      However, six taxa found only in rivers >=28% glacier cover may require
      reclassification of their Red List conservation status, as this habitat is
      threatened by deglaciation. Our identification of clear links between decreasing
      glacier cover and river diatom biodiversity suggests there could be significant
      reorganization of river ecosystems with deglaciation, for example, through
      alterations to primary production, biogeochemical cycles, and the shifting
      resource base of alpine freshwater food webs which lack significant allochthonous
      energy inputs.

PMID- 30230661
TI  - Bacterial community response to a preindustrial-to-future CO2 gradient is limited
      and soil specific in Texas Prairie grassland.
AB  - Rising atmospheric CO2 concentration directly stimulates plant productivity and
      affects nutrient dynamics in the soil. However, the influence of CO2 enrichment
      on soil bacterial communities remains elusive, likely due to their complex
      interactions with a wide range of plant and soil properties. Here, we
      investigated the bacterial community response to a decade long preindustrial-to
      future CO2 gradient (250-500 ppm) among three contrasting soil types using 16S
      rRNA gene amplicon sequencing. In addition, we examined the effect of seasonal
      variation and plant species composition on bacterial communities. We found that
      Shannon index (H') and Faith's phylogenetic diversity (PD) did not change in
      response to the CO2 gradient (R2  = 0.01, p > 0.05). CO2 gradient and season also
      had a negligible effect on overall community structure, although silty clay soil
      communities were better structured on a CO2 gradient (p < 0.001) among three
      soils. Similarly, CO2 gradient had no significant effect on the relative
      abundance of different phyla. However, we observed soil-specific variation of CO2
      effects in a few individual families. For example, the abundance of Pirellulaceae
      family decreased linearly with CO2 gradient, but only in sandy loam soils.
      Conversely, the abundance of Micromonosporaceae and Gaillaceae families increased
      with CO2 gradient in clay soils. Soil water content (SWC) and nutrient properties
      were the key environmental constraints shaping bacterial community structure, one
      manifestation of which was a decline in bacterial diversity with increasing SWC.
      Furthermore, the impact of plant species composition on community structure was
      secondary to the strong influence of soil properties. Taken together, our
      findings indicate that bacterial communities may be largely unresponsive to
      indirect effects of CO2 enrichment through plants. Instead, bacterial communities
      are strongly regulated by edaphic conditions, presumably because soil differences
      create distinct environmental niches for bacteria.

PMID- 30230662
TI  - Specialized pro-resolving lipid mediators in experimental periodontitis: A
      systematic review.
AB  - Recently, several studies demonstrated the potential of using specialized pro
      resolving lipid mediators (SPMs), as a novel approach, in treating periodontitis
      in pre-clinical models. This review aimed to systematically evaluate the
      biological actions of SPMs on periodontal tissues in animals with experimentally
      induced periodontitis. This systematic review was performed by following the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines. Studies were searched in three databases. Meta-analysis was not
      performed because of the data heterogeneity. Study quality was assessed using
      Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) Risk of
      Bias tool. Six studies using an experimental periodontitis model to test the
      efficacy of SPMs were selected. Resolvin E1 and lipoxins were topically applied
      to treat experimental periodontitis. Alveolar bone loss could be significantly
      prevented and regenerated by applying SPMs, when compared to the control group.
      The dosages of SPMs and the periods of disease induction varied based on the pre
      clinical model employed. Two studies further demonstrated the positive shift in
      microbial composition, in line with positive shift in inflammatory status, that
      are regulated by SPMs. Clinical studies are needed to optimize the application of
      SPMs in treating periodontal diseases in humans.

PMID- 30230663
TI  - Predicting X-ray solution scattering from flexible macromolecules.
AB  - Wide-angle X-ray solution scattering (WAXS) patterns contain substantial
      information about the structure and dynamics of a protein. Solution scattering
      from a rigid protein can be predicted from atomic coordinate sets to within
      experimental error. However, structural fluctuations of proteins in solution can
      lead to significant changes in the observed intensities. The magnitude and form
      of these changes contain information about the nature and spatial extent of
      structural fluctuations in the protein. Molecular dynamics (MD) simulations based
      on a crystal structure and selected force field generate models for protein
      internal motions, and here we demonstrate that they can be used to predict the
      impact of structural fluctuations on solution scattering data. In cases where the
      observed and calculated intensities correspond, we can conclude that the X-ray
      scattering provides direct experimental validation of the structural and MD
      results. In cases where calculated and observed intensities are at odds, the
      inconsistencies can be used to determine the origins of these discrepancies. They
      may be because of overestimates or underestimates of structural fluctuations in
      MD simulations, under-sampling of the structural ensemble in the simulations,
      errors in the structural model, or a mismatch between the experimental conditions
      and the parameters used in carrying out the MD simulation.

PMID- 30230664
TI  - Fire severity effects on soil carbon and nutrients and microbial processes in a
      Siberian larch forest.
AB  - Fire frequency and severity are increasing in tundra and boreal regions as
      climate warms, which can directly affect climate feedbacks by increasing carbon
      (C) emissions from combustion of the large soil C pool and indirectly via changes
      in vegetation, permafrost thaw, hydrology, and nutrient availability. To better
      understand the direct and indirect effects of changing fire regimes in northern
      ecosystems, we examined how differences in soil burn severity (i.e., extent of
      soil organic matter combustion) affect soil C, nitrogen (N), and phosphorus (P)
      availability and microbial processes over time. We created experimental burns of
      three fire severities (low, moderate, and high) in a larch forest in the
      northeastern Siberian Arctic and analyzed soils at 1, 8 days, and 1 year
      postfire. Labile dissolved C and N increased with increasing soil burn severity
      immediately (1 day) postfire by up to an order of magnitude, but declined
      significantly 1 week later; both variables were comparable or lower than unburned
      soils by 1 year postfire. Soil burn severity had no effect on P in the organic
      layer, but P increased with increasing severity in mineral soil horizons. Most
      extracellular enzyme activities decreased by up to 70% with increasing soil burn
      severity. Increasing soil burn severity reduced soil respiration 1 year postfire
      by 50%. However, increasing soil burn severity increased net N mineralization
      rates 1 year postfire, which were 10-fold higher in the highest burn severity.
      While fires of high severity consumed approximately five times more soil C than
      those of low severity, soil C pools will also be driven by indirect effects of
      fire on soil processes. Our data suggest that despite an initial increase in
      labile C and nutrients with soil burn severity, soil respiration and
      extracellular activities related to the turnover of organic matter were greatly
      reduced, which may mitigate future C losses following fire.

PMID- 30230665
TI  - Physician-Assisted Death: Ethical Implications for Emergency Physicians.
AB  - Physician-assisted death (PAD) has long been a strongly debated moral and public
      policy issue in the United States (US), and an increasing number of jurisdictions
      have legalized this practice under certain circumstances. In light of changing
      terminology, laws, public and professional attitudes, and the availability of
      published data about the practice, we review key concepts and terms in the
      ongoing PAD debate, moral arguments for and against PAD, the current legal status
      of PAD in the US and in other nations, and data on the reported experience with
      PAD in those US jurisdictions where it is a legal practice. We then identify
      situations in which emergency physicians (EPs) may encounter patients who request
      PAD or have attempted to end their lives with physician assistance and consider
      EP responses in those situations. Based on our analysis, we offer recommendations
      for emergency medical practice and professional association policy. This article
      is protected by copyright. All rights reserved.

PMID- 30230666
TI  - Telemedical Interventional Management in Heart Failure II (TIM-HF2), a
      randomised, controlled trial investigating the impact of telemedicine on
      unplanned cardiovascular hospitalisations and mortality in heart failure
      patients: study design and description of the intervention.
AB  - BACKGROUND: Heart failure (HF) is a complex, chronic condition that is associated
      with debilitating symptoms, all of which necessitate close follow-up by health
      care providers. Lack of disease monitoring may result in increased mortality and
      more frequent hospital readmissions for decompensated HF. Remote patient
      management (RPM) in this patient population may help to detect early signs and
      symptoms of cardiac decompensation, thus enabling a prompt initiation of the
      appropriate treatment and care before a manifestation of HF decompensation.
      OBJECTIVE: The objective of the present article is to describe the design of a
      new trial investigating the impact of RPM on unplanned cardiovascular
      hospitalisations and mortality in HF patients. METHODS: The TIM-HF2 trial is
      designed as a prospective, randomised, controlled, parallel group, open (with
      randomisation concealment), multicentre trial with pragmatic elements introduced
      for data collection. Eligible patients with HF are randomised (1:1) to either RPM
      + usual care or to usual care only and are followed for 12 months. The primary
      outcome is the percentage of days lost due to unplanned cardiovascular
      hospitalisations or all-cause death. The main secondary outcomes are all-cause
      and cardiovascular mortality. CONCLUSION: The TIM-HF2 trial will provide
      important prospective data on the potential beneficial effect of telemedical
      monitoring and RPM on unplanned cardiovascular hospitalisations and mortality in
      HF patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01878630.

PMID- 30230667
TI  - Potassium control in chronic kidney disease: Implications for neuromuscular
      function.
AB  - In Australia approximately 1.7million adults have evidence of chronic kidney
      disease (CKD). This complex disease can result in a multitude of complications,
      including hyperkalaemia which common and well recognised. . The advent of new
      therapeutics aimed at lowering serum potassium have raised the possibility of
      optimising potassium control to enable greater use of renin-angiotensin
      aldosterone system inhibitors in the management of CKD. Recent studies suggest
      that hyperkalaemia also has implications for peripheral neuropathy in CKD, a
      complication that substantially contributes to patient morbidity. This review
      examines evidence of the relationship between potassium and peripheral neuropathy
      with discussion of clinical implications. We searched PubMed for original and
      review articles using prespecified key words, clinical guidelines and population
      data. The major findings were that contemporary CKD cohorts demonstrate a high
      prevalence of peripheral neuropathy, even in stage 3-4 CKD, including those
      without diabetes. The severity of the problem has been emphasized by an ominous
      rise in foot complications and amputation rates in dialysis patients,
      highlighting the need for increased awareness of the condition in earlier stages
      of CKD and targeted treatment strategies. It is likely that the pathophysiology
      of peripheral neuropathy in CKD is multifaceted with potential influences from
      potassium, vascular abnormalities, diabetes, inflammation and unknown middle
      molecules. Despite these complexities, the relationship between potassium and
      nerve function in dialysis has been well established and recent research in stage
      3-4 CKD suggests that assertive potassium control may improve neuromuscular
      outcomes in CKD. These small studies should be confirmed in large, multicenter
      settings. This article is protected by copyright. All rights reserved.

PMID- 30230668
TI  - Treatment of the Mayer-Rokitansky-Kuster-Hauser syndrome with autologous in vitro
      cultured vaginal tissue: descriptive study of long-term results and patient
      outcomes.
AB  - OBJECTIVE: Evaluating sexual function and quality of life (QoL) in patients
      treated with a modified Abbe-McIndoe technique using in vitro cultured autologous
      vaginal mucosa. DESIGN: Descriptive study. SETTING: Policlinico Umberto I,
      Sapienza University of Rome. POPULATION: From 2006 to 2016, 39 women affected by
      Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) underwent vaginoplasty at our
      centre using a modified Abbe-McIndoe technique with in vitro cultured autologous
      vaginal tissue. METHODS: For each patient, vaginal tissue was obtained by full
      thickness biopsy of the vaginal vestibule. Following enzymatic dissociation,
      cells were cultured for 2-3 weeks before the transplant. MAIN OUTCOME MEASURES:
      Each patient completed two validated questionnaires to quantify sexual function
      and QoL: the Female Sexual Function Index (FSFI), administered at 12, 36, and 60
      months, and the Psychological General Well Being Index (PGWBI) administered at 0,
      6, and 36 months after surgery. RESULTS: Twelve months after surgery, 29 patients
      were engaging in regular sexual activity. The FSFI test results showed a
      satisfactory sexual function compared to the general population, with median
      values of 25.85 (range 4.6-30.5) at 12 months, 27.2 (range 4.4-33.6) at 36
      months, and 29.6 (range 23.9-33.6) at 60 months. The PGWBI questionnaire showed a
      median score of 420.5 (range 108-540) before surgery, and 459 (range 252-533) at
      the 60-month follow-up. CONCLUSIONS: Vaginoplasty performed with the use of
      autologous vaginal tissue, besides ensuring a long-term satisfying sex life,
      helps in achieving an improvement in QoL that is maintained over time. TWEETABLE
      ABSTRACT: Vaginoplasty using in vitro vaginal tissue ensures a satisfactory
      sexual function and improves quality of life.

PMID- 30230669
TI  - Access, knowledge and experience with FDG-PET/CT in infection management: a
      survey of Australia and New Zealand infectious diseases physicians and
      microbiologists.
AB  - BACKGROUND: Despite FDG-PET/CT being funded only for staging and restaging of
      some malignancies in Australia, there is evidence of benefit of FDG-PET/CT for
      infection indications such as pyrexia of unknown origin (PUO), prolonged
      neutropenic fever (NF) and prosthetic device infection. AIMS: To evaluate the
      current knowledge, utilisation of and gaps in access to FDG-PET/CT for infectious
      indications by Australasian infectious diseases (ID) physicians and
      microbiologists. METHODS: An online survey was administered to ID and
      microbiology doctors practicing in adult medicine in Australia and New Zealand
      via two established email networks. Using targeted questions and case-based
      examples, multiple themes were explored, including: access to FDG-PET/CT, use and
      perceived benefit of FDG-PET/CT in diagnosis and monitoring of non-malignant
      conditions such as NF and PUO, and barriers to clinical use of FDG-PET/CT.
      RESULTS: A response was received from 120 participants across all states and
      territories. Onsite and offsite FDG-PET/CT access was 63% and 31%, respectively.
      Eighty-six per cent reported using FDG-PET/CT for one or more infection
      indications and all had found it clinically useful, with common indications being
      PUO, prosthetic device infections and use in the immunocompromised host for
      prolonged NF and IFI. Thirty-eight per cent reported barriers in accessing FDG
      PET/CT for infection indications and 76% would utilise FDG-PET/CT more frequently
      if funding existed for infection indications. CONCLUSIONS: Access to FDG-PET/CT
      in Australia and New Zealand is modest and is limited by lack of reimbursement
      for infection indications. There is discrepancy between recognised ID indications
      for FDG-PET/CT and funded indications. This article is protected by copyright.
      All rights reserved.

PMID- 30230670
TI  - Total Syntheses of Bisdehydroneostemoninine and Bisdehydrostemoninine by
      Catalytic Carbonylative Spirolactonization.
AB  - The first total syntheses of the stemona alkaloids bisdehydroneostemoninine and
      bisdehydrostemoninine in racemic forms have been achieved. The synthetic strategy
      features a novel palladium-catalyzed carbonylative spirolactonization of a
      hydroxycyclopropanol to rapidly construct the oxaspirolactone moiety. It also
      features a Lewis acid promoted tandem Friedel-Crafts cyclization and
      lactonization to form the 5-7-5 tricyclic core of the target stemona alkaloids.

PMID- 30230671
TI  - Transcript Profiling of MRSA Biofilms Treated with a Halogenated Phenazine
      Eradicating Agent: A Platform for Defining Cellular Targets and Pathways Critical
      to Biofilm Survival.
AB  - Bacterial biofilms are surface-attached communities of non-replicating bacteria
      innately tolerant to antibiotics. Biofilms display differential gene expression
      profiles and physiologies as compared to their planktonic counterparts; however,
      their biology remains largely unknown. In this study, we used a halogenated
      phenazine (HP) biofilm eradicator in transcript profiling experiments (RNA-seq)
      to define cellular targets and pathways critical to biofilm viability. WoPPER
      analysis with time-course validation (RT-qPCR) revealed that HP-14 induces rapid
      iron starvation in MRSA biofilms, as evident by the activation of iron
      acquisition gene clusters in 1 hour. Serine proteases and oligopeptide
      transporters were also found to be up-regulated, whereas glycolysis, arginine
      deiminase, and urease gene clusters were down-regulated. KEGG analysis revealed
      that HP-14 impacts metabolic and ABC transporter functional pathways. These
      findings suggest that MRSA biofilm viability relies on iron homeostasis.

PMID- 30230672
TI  - Boosting the Electrochemical Performance of Li-S Batteries with a Dual
      Polysulfides Confinement Strategy.
AB  - Lithium-sulfur (Li-S) batteries have attracted more and more attention because
      they represent one of the most promising candidates to satisfy emerging energy
      storage demands. The biggest challenge regarding the application of the Li-S
      battery is to suppress the polysulfide shuttle while maintaining a high sulfur
      loading mass. Here, a dual polysulfide confinement strategy is designed by
      confinement of sulfur in polydopamine-coated MXene nanosheets (denoted as
      S@Mxe@PDA) that performs as a high-performance cathode for Li-S cells owing to
      their inherently high underlying metallic conductivity and chemical bonding and
      strong chemical adsorption to lithium polysulfides (LPs). This dual LPs
      confinement strategy is supported by the results of density functional theory
      calculations. It is demonstrated that the S@Mxe@PDA cathode exhibits outstanding
      electrochemical properties, including high reversible capacity (1044 mAh g-1
      after 150 cycles at 0.2 C), superior rate capability (624 mAh g-1 at 6 C) and
      excellent cycling stability (556 mAh g-1 after 330 cycles at 0.5 C with 4.4 mg cm
      2 sulfur loading). This work offers a facile and effective method for boosting Li
      S batteries into practical applications.

PMID- 30230673
TI  - A Stereodynamic Redox-Interconversion Network of Vicinal Tertiary and Quaternary
      Carbon Stereocenters in Hydroquinone-Quinone Hybrid Dihydrobenzofurans.
AB  - Reversible redox processes involving hydroquinones and quinones are ubiquitous in
      biological reaction networks, materials science, and catalysis. While extensively
      studied in intermolecular settings, less is known about intramolecular scenarios.
      Herein, we report hydroquinone-quinone hybrid molecules that form two
      stereocenter dihydrobenzofurans via intramolecular cyclization under
      thermodynamic control. A pi-methylhistidine peptide-catalyzed kinetic resolution
      allowed us to study the stereodynamic behavior of enantio- and diastereo-enriched
      dihydrofurans. In the course of this study, it was revealed that a reversible
      intramolecular redox-interconversion network connects all four possible
      stereoisomers via inversion of a quaternary carbon stereocenter without achiral
      intermediates. As a result, these findings on hydroquinone-quinone hybrid
      molecules provide insights into potential natural origin and synthetic access of
      the common dihydrobenzofuran motif.

PMID- 30230675
TI  - Blavatnik Awards for Young Scientists: K. K. Devaraj, C. E. Diesendruck, and A.
      L. Goodwin / FCI Dozentenpreise: F. Dielmann, F. Wurm, and B. Morandi.

PMID- 30230674
TI  - Magnetite Fe3 O4 Has no Intrinsic Peroxidase Activity, and Is Probably not
      Involved in Alzheimer's Oxidative Stress.
AB  - Despite stated in some highly cited articles, magnetite is devoided of peroxidase
      activity. In fact, this very stable mixed valence FeII O?FeIII 2 O3 complex is
      not catalytically competent to oxidize standard peroxidase substrates, especially
      at the biologically relevant pH value of 7.4. In addition, magnetite whose
      deleterious redox activity has been suspected in Alzheimer's disease brain
      damages, does not significantly interact with amyloid peptide Abeta in vitro, and
      is not able to induce, either in the presence or absence of Abeta, the reductive
      activation of dioxygen, the first step of an oxidative stress. In fact, this
      highly insoluble mineral iron derivative is probably not involved in the
      oxidative damage of brain neurons of patients with AD.

PMID- 30230676
TI  - The Living Dead: Mitochondria and Metabolic Arrest.
AB  - Mitochondria are not just the powerhouses of the cell; these 'end of function'
      organelles are crucial components of cellular physiology and influence many
      central metabolic and signaling pathways that support complex multicellular life.
      Not surprisingly, these organelles play vital roles in adaptations for extreme
      survival strategies including hibernation and freeze tolerance, both of which are
      united by requirements for a strong reduction and reprioritization of metabolic
      processes. To facilitate metabolic rate depression, adaptations of all aspects of
      mitochondrial function are required, including; energetics, physiology,
      abundance, gene regulation, and enzymatic controls. This review discusses these
      factors with a focus on the stress-specific nature of mitochondrial genes and
      transcriptional regulators, and processes including apoptosis and chaperone
      protein responses. We also analyze the regulation of glutamate dehydrogenase and
      pyruvate dehydrogenase, central mitochondrial enzymes involved in coordinating
      the shifts in metabolic fuel use associated with extreme survival strategies.
      Finally, an emphasis is given to the novel mitochondrial research areas of
      microRNAs, peptides, epigenetics, and gaseous mediators and their potential roles
      in facilitating hypometabolism. (c) 2018 IUBMB Life, 70(12):1260-1266, 2018.

PMID- 30230677
TI  - Carving Out Pores in Redox-Active One-Dimensional Coordination Polymers.
AB  - Reduction of the insulating one-dimensional coordination polymer [Cu(abpy)PF6 ]n
      , 1 a(PF6 ), (abpy=2,2'-azobispyridine) yields the conductive, porous polymer
      [Cu(abpy)]n , 2 a. Pressed pellets of neutral 2 a exhibit a conductivity of 0.093
      S cm-1 at room temperature and a Brunauer-Emmett-Teller (BET) surface area of 56
      m2  g-1 . Fine powders of 2 a have a BET surface area of 90 m2  g-1 . Cyclic
      voltammetry shows that the reduction of 1 a(PF6 ) to 2 a is quasi-reversible,
      indicative of facile charge transfer through the bulk material. The BET surface
      area of the reduced polymer 2 can be controlled by changing the size of the
      counteranion X in the cationic [Cu(abpy)X]n . Reduction of [Cu(abpy)X]n with X=Br
      (2 b) or BArF (2 c; BArF =tetrakis(3,5-bis(trifluoromethyl)phenyl)), affords
      [Cu(abpy)]n polymers with surface areas of 60 and 200 m2  g-1 , respectively.

PMID- 30230678
TI  - A retrospective study of an alternative technique for implant repositioning in
      the maxillary esthetic region.
AB  - BACKGROUND: Implant-bone block segment repositioning may be an option of
      treatment for patients with vertical alveolar bone atrophy. PURPOSE: To assess
      implant-bone block movement, gingival outcome and the subjective appreciation of
      patients after an alternative treatment of an implant-bone block segment
      repositioning in the maxillary esthetic region. MATERIALS AND METHODS: Patients
      who underwent implant-bone block segment relocation in areas of vertical alveolar
      bone atrophy in the anterior esthetic region were assessed. The outcome measures
      were implant failure, complications after initial loading, vertical bone
      augmentation, papilla index, width of the keratinized mucosa, and patient
      satisfaction. RESULTS: Twenty-five implants in nine consecutive patients were
      included in this study. During the follow-up period, only one implant failed.
      Vertical bone augmentation ranged from 3.0 to 8.4 mm (mean 4.9 mm). A significant
      improvement (P < .001) in the papilla index was observed, improving the esthetic
      outcome. Six patients (66.6%) had more than 2 mm of keratinized mucosa and all of
      the patients were satisfied with the treatment. CONCLUSIONS: The esthetics and
      functional gingival outcome of oral rehabilitation in areas with vertical
      alveolar bone atrophy can be successfully improved with the presented technique,
      which had a high overall implant survival rate within a short period.

PMID- 30230680
TI  - Automation in radiation oncology - cautionary considerations in the push for
      planning efficiency.

PMID- 30230681
TI  - Autogenous DDM versus Bio-Oss granules in GBR for immediate implantation in
      periodontal postextraction sites: A prospective clinical study.
AB  - PURPOSE: Demineralized dentin matrix (DDM) from the patient's own extracted
      healthy tooth can be recycled as an autogenous biomaterial for reconstructive
      dentistry. The aim of the present study was to evaluate the clinical efficacy of
      autogenous DDM versus Bio-Oss granules in guided bone regeneration (GBR) for
      immediate implantation in periodontal postextraction sites. MATERIALS AND
      METHODS: From November 2015 to March 2017, patients referred to the Foshan
      Stomatology Hospital, who had been diagnosed with severe periodontitis of the
      posterior mandibular tooth and agreed to dental implant treatment, were
      consecutively included. The patients were randomly allocated to the DDM group,
      treated with immediate implantation + GBR with autogenous DDM granules from the
      extracted tooth, or the BIO group, treated with immediate implantation + GBR with
      Bio-Oss granules. The implant stability and marginal bone resorption were
      measured immediately, at 6 and 18 months after surgery. RESULTS: Forty patients
      (45 implants) were included. Except 2 cases with wound infection, 43 implants did
      not have postoperative complications and achieved a satisfactory outcome after 1
      year prosthetic loading. There was no statistically significant difference
      between the 2 groups in implant stability quotient values and marginal bone
      resorption. CONCLUSION: The autogenous DDM granules prepared at the chairside
      after extractions could act as an excellent readily available alternative to bone
      graft material in GBR, even for implantation of severe periodontitis cases.

PMID- 30230679
TI  - Chemotherapy and biologic use in the routine management of metastatic colorectal
      cancer in Australia: is clinical practice following the evidence?
AB  - BACKGROUND: Emerging evidence on the optimal use of chemotherapy and biologics in
      patients with metastatic colorectal cancer (mCRC) should impact management in
      routine care. Recent studies have demonstrated benefits for initial triplet
      chemotherapy (FOLFOXIRI) and for initial treatment with an epidermal growth
      factor receptor inhibitor (EGFRi) in patients with a RAS wild type tumour and a
      left-sided primary. AIM: To explore evolving patterns of mCRC care over time in
      Australia. METHODS: We analysed data from the Treatment of Recurrent and Advanced
      Colorectal Cancer (TRACC) registry. RESULTS: From July 2009 to December 2017,
      2552 mCRC patients were entered into the TRACC registry. Of 1585 patients who
      initially underwent chemotherapy, treatment was with a doublet in 76%. FOLFOXIRI
      was given to 22 patients (1.4%), mostly young patients and those with potentially
      resectable disease. Along with first-line chemotherapy, 61% received bevacizumab,
      while 3.3% received an EGFRi, predominantly over the last two years. Within the
      KRAS wild-type left-sided tumour cohort, EGFRi use increased from 9% in 2015 to
      37% in 2017. Across treatment sites, there was wide variation in the utilization
      of FOLFOXIRI and EGFRi therapy; bevacizumab use was more consistent. A clear
      impact on survival outcomes from these regimens is not evident, potentially due
      to multiple confounders. CONCLUSION: Doublet chemotherapy plus bevacizumab
      remains the dominant initial strategy, with limited uptake of triplet
      chemotherapy and of EGFRi. Potential explanations include uncertainty about the
      significance of post-hoc analyses for EGFRi and concerns regarding adverse events
      for both strategies. This article is protected by copyright. All rights reserved.

PMID- 30230682
TI  - A fibrin-coated pericardial extracellular matrix prevented heart adhesion in a
      rat model.
AB  - As most surgical treatments pose a risk of tissue adhesion, methods to prevent
      adhesion are needed across various surgical fields. In this study, we
      investigated the use of a decellularized pericardium with fibrin glue to prevent
      rat heart adhesion. Porcine pericardia were decellularized by a high-hydrostatic
      pressure method. Cells adhered to the resulting pericardial extracellular matrix
      (ECM) during an in vitro cell-seeding test, but fibrin-coated pericardial ECM
      showed reduced cell adhesion. In a rat surgical model of heart adhesion, the
      fibrin-coated pericardial ECM did not adhere to the heart and mesothelial cell
      adhesion was observed on the ECM surface. Notably, the anti-adhesion effect of
      fibrin-coated pericardial ECM was observed 4 weeks after surgery. These results
      support the utility of fibrin-coated pericardial ECM as an adhesion prevention
      material for cardiovascular surgery. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res B Part B: Appl Biomater 00B: 000-000, 2018.

PMID- 30230683
TI  - Clustering of Lifestyle Risk Factors in Acute Coronary Syndrome: Prevalence and
      Change after the First Event.
AB  - BACKGROUND: Healthy lifestyles are modifiable risk factors for acute coronary
      syndrome (ACS) onset and recurrence. While unhealthy lifestyles tend to cluster
      together within the general healthy population, little is known about the
      prevalence and clustering of these behaviours in people with ACS before and after
      the first acute event. The aim of this study was to identify lifestyle profiles
      of patients with ACS and to explore their change after their first coronary
      event. METHODS: Three hundred and fifty-six patients completed self-report
      measures of healthy habits at the beginning of cardiac rehabilitation and 6
      months later. By adopting a person-oriented approach, we analysed lifestyle
      clustering and its change over time. Differences in depression, anxiety, and
      negative illness perception among lifestyle profiles were assessed. RESULTS: We
      identified seven profiles, ranging from more maladaptive to healthier clusters.
      Findings showed a strong interrelation among unhealthy habits in patients. We
      highlighted a moderate individual and group stability of cluster membership over
      time. Moreover, unhealthier lifestyle profiles were associated with higher levels
      of depression, anxiety, and negative illness perception. CONCLUSION: These
      results may have implications for the development and implementation of
      multimodal interventions addressing wider-ranging improvement in lifestyles by
      targeting multiple unhealthy behaviours in patients with ACS.

PMID- 30230684
TI  - Industrial-scale fabrication of an osteogenic and antibacterial PLA/silver-loaded
      calcium phosphate composite with significantly reduced cytotoxicity.
AB  - In this study, we report an industrial-scale fabrication method of a
      multifunctional polymer composite as a scaffold material for bone tissue
      engineering. This study successfully demonstrated the potential of applying
      industrial polymer processing technologies to produce specially functionalized
      tissue engineering scaffolds. With the inclusion of a newly synthesized
      multifunctional additive, silver-doped-calcium phosphate (silver-CaP), the
      composite material exhibited excellent osteogenic inducibility of human adipose
      derived stem cells (hASC) and satisfactory antibacterial efficacy against
      Escherichia coli and Staphylococcus aureus. Also, relative to previously reported
      methods of direct loading silver particles into polymeric materials, our
      composite exhibited significantly reduced silver associated cytotoxicity. The
      enhanced biocompatibility could be a significant advantage for materials to be
      used for regenerative medicine applications where clinical safety is a major
      consideration. The impact of different silver loading methodologies on hASC'
      osteogenic differentiation was also studied. Overall, the results of this study
      indicate a promising alternative approach to produce multifunctional scaffolds at
      industrial-scale with higher throughput, lower cost, and enhanced
      reproducibility. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B:
      Appl Biomater, 2018.

PMID- 30230685
TI  - Antibacterial 3D bone scaffolds for tissue engineering application.
AB  - Open bone fractures are not only difficult to heal but also are at a high risk of
      infections. Annual cases of fractures which result from osteoporosis amount to
      approximately 9 million. Endogenously released nitric oxide (NO) has been shown
      to play a role in osteogenic differentiation in addition to eradicating infection
      against a wide variety of pathogens. In the current work, antimicrobial NO
      releasing 3D bone scaffolds were fabricated using S-nitroso-N-acetyl
      penicillamine (SNAP) as the NO donor. During fabrication, nano-hydroxyapatite
      (nHA) was added to each of the scaffolds in the concentration range of 10-50 wt %
      in nHA-starch-alginate and nHA-starch-chitosan scaffolds. The mechanical strength
      of the scaffolds increased proportionally to the concentration of nHA and 50 wt %
      nHA-starch-alginate possessed the highest load bearing capacity of 203.95 +/- 0.3
      N. The NO flux of the 50 wt % nHA-starch-alginate scaffolds was found to be 0.50
      +/- 0.06 * 10-10 mol/min/mg initially which reduced to 0.23 +/- 0.02 * 10-10 over
      a 24 h period under physiological conditions. As a result, a 99.76% +/- 0.33%
      reduction in a gram-positive bacterium, Staphylococcus aureus and a 99.80% +/-
      0.62% reduction in the adhered viable colonies of gram-negative bacterium,
      Pseudomonas aeruginosa were observed, which is a significant stride in the field
      of antibacterial natural polymers. The surface morphology and pore size were
      observed to be appropriate for the potential bone cell growth. The material
      showed no toxic response toward mouse fibroblast cells. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B, 2018.

PMID- 30230686
TI  - Piggyback or Cava Replacement: Which Implantation Technique Protects Liver
      Recipients From Acute Kidney Injury and Complications?
AB  - The cava-preserving piggyback (PB) technique requires only partial cava clamping
      during the anhepatic phase in liver transplantation (LT) and, therefore,
      maintains venous return and may hemodynamically stabilize the recipient. Hence,
      it is an ongoing debate whether PB implantation is more protective from acute
      kidney injury (AKI) after LT when compared with a classic cava replacement (CR)
      technique. The aim of this study was to assess the rate of AKI and other
      complications after LT comparing both transplant techniques without the use of
      venovenous bypass. We retrospectively analyzed the adult donation after brain
      death LT cohort between 2008 and 2016 at our center. Liver and kidney function
      and general outcomes including complications were assessed. Overall 378
      transplantations were analyzed, of which 177 (46.8%) were performed as PB and 201
      (53.2%) as CR technique. AKI occurred equally often in both groups. Transient
      renal replacement therapy was required in 22.6% and 22.4% comparing the PB and CR
      techniques (P = 0.81). Further outcome parameters including the complication rate
      were similar in both cohorts. Five-year graft and patient survival were
      comparable between the groups with 81% and 85%, respectively (P = 0.48; P =
      0.58). In conclusion, both liver implantation techniques are equal in terms of
      kidney function and overall complications following LT.

PMID- 30230688
TI  - Nanoarchitectonic-Based Material Platforms for Environmental and Bioprocessing
      Applications.
AB  - The challenges of pollution, environmental science, and energy consumption have
      become global issues of broad societal importance. In order to address these
      challenges, novel functional systems and advanced materials are needed to achieve
      high efficiency, low emission, and environmentally friendly performance. A
      promising approach involves nanostructure-level controls of functional material
      design through a novel concept, nanoarchitectonics. In this account article, we
      summarize nanoarchitectonic approaches to create nanoscale platform structures
      that are potentially useful for environmentally green and bioprocessing
      applications. The introduced platforms are roughly classified into (i) membrane
      platforms and (ii) nanostructured platforms. The examples are discussed together
      with the relevant chemical processes, environmental sensing, bio-related
      interaction analyses, materials for environmental remediation, non-precious metal
      catalysts, and facile separation for biomedical uses.

PMID- 30230687
TI  - Sensory manipulation results in increased dorsolateral prefrontal cortex
      activation during static postural balance in sedentary older adults: An fNIRS
      study.
AB  - BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) is involved with
      allocating attentional resources to maintain postural control. However, it is
      unknown whether age-related structural and functional declines of the DLPFC may
      impair postural control during sensory manipulation. In this study, we aim to
      understand the effects of aging on the DLPFC when sensory cues were removed or
      presented inaccurately (i.e., increased sensory complexity) during the sensory
      orientation test (SOT). METHODS: Twenty young (18-25 years) and 18 older (66-73
      years) healthy adults were recruited to undertake the SOT, which consisted of six
      conditions aimed at removing or disrupting the visual, vestibular, and
      proprioceptive senses. During these six SOT conditions, functional near-infrared
      spectroscopy (fNIRS), consisting of eight transmitter-receiver optode pairs (four
      channels over the left and right DLPFC), was used to measure hemodynamic
      responses (i.e., changes in oxy- [O2 Hb] and deoxyhemoglobin [HHb]) from the
      bilateral DLPFC. RESULTS: Our results show an increase in bilateral DLPFC
      activation (i.e., increase in O2 Hb and concomitant smaller decrease in HHb) with
      increasing sensory complexity in both young and older adults. The increase in
      left and right DLPFC activation during more complex sensory conditions was
      greater, which was concomitant with reduced balance performance in older adults
      compared to younger adults. Furthermore, we observed a right lateralized DLPFC
      activation in younger adults. Finally, a significant positive association was
      observed between balance performance and increased bilateral DLPFC activation
      particularly for SOT conditions with greater sensory disruptions. CONCLUSION: Our
      findings highlight the involvement of the DLPFC in maintaining postural control,
      particularly during complex sensory tasks, and provide direct evidence for the
      role of the DLPFC during postural control of a clinically relevant measure of
      balance.

PMID- 30230690
TI  - Recent Developments in the Biosynthesis of Cu-based Recyclable Nanocatalysts
      Using Plant Extracts and their Application in the Chemical Reactions.
AB  - Copper nanoparticles (NPs) are one of the most commercialized nanomaterials. From
      the standpoint of nanotechnology copper-based nanostructured materials have many
      applications in biological process, folk medicine, electronics, and industrial
      fields. With growing concern regarding the energy crisis and problems of chemical
      and physical procedures to prepare the metal nanoparticles, efforts for
      alternative traditional chemistry attracted particular considerations. A
      widespread of researches have studied on biological methods which do not generate
      hazardous waste and therefore, don't need the purification processes. Plants
      could be remarkably valuable to exploring the biogenic synthesis of metal
      nanoparticles. The aim of this review is to provide further insight in to
      connections between plant extracts and synthesis of copper NPs. The utilization
      of living plants for biosynthesis of metal nanoparticles (MNPs) is a cost
      effective and eco-friendly procedure. To date, the obtained results demonstrated
      several aspects of the plant physiology and their relations to nanoparticle
      synthesis. This work describes the state of the art and future challenges in
      green synthesis of copper NPs. This review has proven recent elevation in the
      green synthesis of Cu NPs, CuO NPs, Cu2 O NPs, CuS NPs, CuAl2 O4 and immobilized
      copper nanoparticles on the numerous supports such as Natrolite, bentonite,
      perlite, ZnO, MgO, MnO2 , reduced graphene oxide (RGO), and Fe3 O4 by a wide
      range of plant extracts. Therefore, detailed description of green synthesis and
      stabilizing agents concerning copper nanoparticles using these green sources is
      presented. Also, the catalytic activities of synthesized Cu-based recyclable
      nanocatalysts using various plant extracts in several chemical reactions such as
      oxidation, reduction, hydration, cyanation, cycloaddition, and coupling reactions
      were consciously investigated.

PMID- 30230689
TI  - Nitrosylruthenium Complexes as Polymerization Catalysts for Acrylonitrile in DMF.
AB  - Nitrosylruthenium complexes bearing two 2,2'-bipyridine (bpy) or 2
      pyridinecarboxylate (pyc) ligands, [Ru(NO)X(bpy)2 ]3+ (X=CH3 CN, CH2 =CHCN, H2 O,
      Cl, ONO2 ) and [Ru(NO)(OH2 )(pyc)2 ]+ , were used as catalysts for the
      polymerization of acrylonitrile in N,N-dimethylformamide (DMF) under air without
      initiators to obtain polyacrylonitrile (PAN) with a high molecular weight and a
      narrow molecular weight distribution.

PMID- 30230691
TI  - Promoting Youth Mental Health via Text-Messages: A New Zealand Feasibility Study.
AB  - BACKGROUND: A growing body of research has documented the positive effects of
      gratitude programs on participants' mental health and well-being. For children
      and adolescents, these programs typically rely on school-based group designs tied
      with a health curriculum, whereas innovative technology-based programs are
      relatively understudied. METHODS: This experiment investigated the feasibility
      and efficacy of a gratitude text-messaging program for promoting adolescent
      mental health relative to a positive reflective control condition. RESULTS: Young
      people showed positive changes over the course of the program in their general
      sense of gratitude, subjective well-being, and reduced depressive symptoms, with
      some evidence that those with higher levels of depressive symptoms benefited more
      from the gratitude program. However, there were no significant differences across
      the two groups in the magnitude of these mental health changes. Participants in
      both conditions valued and were highly engaged with the interactive text
      messaging approach. CONCLUSION: This interactive e-health promotion strategy
      seemed to promote strong engagement and showed promising effectiveness with young
      people, with some challenges to feasibility due to the labor intensive nature of
      sending and responding to a large number of text-messages. The importance of
      carefully considering risk management strategies when developing such programs
      was also highlighted.

PMID- 30230693
TI  - Primary pulmonary melanoma diagnosed by semi-rigid thoracoscopy.

PMID- 30230692
TI  - Comfort and Attitudes Towards Robots Among Young, Middle-Aged, and Older Adults:
      A Cross-Sectional Study.
AB  - PURPOSE: To explore the social impact of, comfort with, and negative attitudes
      towards robots among young, middle-aged, and older adults in the United States.
      DESIGN: Descriptive, cross-sectional. Conducted in 2014-2015 in an urban area of
      the western United States using a purposive sample of adults 18 years of age or
      older. METHODS: Respondents completed a survey that included the Negative
      Attitudes Toward Robots Scale (NARS) and two questions taken or modified from the
      European Commission's Autonomous System 2015 Report. Analyses were conducted to
      compare perceptions and demographic factors by age groups (young adults:18-44,
      middle-aged adults: 45-64, and older adults: >65 years old). FINDINGS: Sample
      included 499 individuals (n = 322 age 18-44 years, n = 50 age 45-64 years, and n
      = 102 age 65-98 years). There were no significant differences between age groups
      for 9 of the 11 items regarding social impact of robots and comfort with robots.
      There were no significant differences by age groups for 9 of the 14 items in the
      NARS. Among those items with statistically significant differences, the mean
      scores indicate similar sentiments for each group. CONCLUSIONS: Older, middle
      aged, and younger adults had similar attitudes regarding the social impact of and
      comfort with robots; they also had similar negative attitudes towards robots.
      Findings dispel current perceptions that older adults are not as receptive to
      robots as other adults. This has implications for nurses who integrate supportive
      robots in their practice. CLINICAL RELEVANCE: Nurses working in clinical and
      community roles can use these findings when developing and implementing robotic
      solutions. Understanding attitudes towards robots can support how, where, and
      with whom robots can be used in nursing practice.

PMID- 30230694
TI  - Effect of a High-Fat Meal on the Pharmacokinetics of the HIV Integrase Inhibitor
      Cabotegravir.
AB  - Cabotegravir is an integrase inhibitor in clinical development for the treatment
      and prevention of HIV infection using oral tablets for short-term, lead-in use
      before subsequent administration of a long-acting injectable formulation. This
      phase 1, single-center, randomized, 2 * 2 crossover study evaluated the effect of
      a high-fat meal on the pharmacokinetics (PK) of oral cabotegravir. Healthy adults
      received oral cabotegravir 30 mg as a single dose on 2 separate occasions, either
      after fasting or following a high-fat meal (~53% fat, ~870 kcal). Safety
      evaluations and serial PK samples were collected, and a mixed-effects model was
      used to determine within-participant treatment comparison of noncompartmental PK
      parameters. Twenty-four patients were enrolled and had a mean body mass index of
      25.6 kg/m2 ; 67% were male. Compared with the fasting state, coadministration of
      cabotegravir with a high-fat meal increased plasma cabotegravir area under the
      concentration-time curve and maximal drug concentration, each by 14%. The slight
      14% to 17% increase in exposure associated with a high-fat, high-calorie meal was
      not considered clinically significant. No grade 3/4 adverse events (AEs), drug
      related AEs, or AEs leading to discontinuation were reported.

PMID- 30230695
TI  - Molecular tools enabling pennycress (Thlaspi arvense) as a model plant and
      oilseed cash cover crop.
AB  - Thlapsi arvense L. (pennycress) is being developed as a profitable oilseed cover
      crop for the winter fallow period throughout the temperate regions of the world,
      controlling soil erosion and nutrients run-off on otherwise barren farmland. We
      demonstrate that pennycress can serve as a user-friendly model system akin to
      Arabidopsis that is well-suited for both laboratory and field experimentation. We
      sequenced the diploid genome of the spring-type Spring 32-10 inbred line (1C DNA
      content of 539 Mb; 2n = 14), identifying variation that may explain phenotypic
      differences with winter-type pennycress, as well as predominantly a one-to-one
      correspondence with Arabidopsis genes, which makes translational research
      straightforward. We developed an Agrobacterium-mediated floral dip transformation
      method (0.5% transformation efficiency) and introduced CRISPR-Cas9 constructs to
      produce indel mutations in the putative FATTY ACID ELONGATION1 (FAE1) gene,
      thereby abolishing erucic acid production and creating an edible seed oil
      comparable to that of canola. We also stably transformed pennycress with the
      Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) gene, producing low
      viscosity acetyl-triacylglycerol-containing seed oil suitable as a diesel-engine
      drop-in fuel. Adoption of pennycress as a model system will accelerate oilseed
      crop translational research and facilitate pennycress' rapid domestication to
      meet the growing sustainable food and fuel demands.

PMID- 30230696
TI  - Endovascular clot retrieval in acute stroke with large ischemic core is not
      always associated with poor outcomes.
AB  - BACKGROUND: The benefits of endovascular clot retrieval (ECR) for anterior
      circulation stroke with large ischemic cores remain uncertain. In spite of recent
      pooled analysis of randomized controlled studies, conclusions regarding the fate
      of large ischemic cores cannot be reached given the small number of included
      patients. METHODS: This was a single centre retrospective study of patients
      treated with ECR in the period 2012 to 2017. The inclusion criteria were anterior
      circulation stroke with symptom onset less than 6 hours, baseline CT perfusion
      and 90 day clinical follow up defined by the Modified Rankin Score (mRS).
      RESULTS: 261 patients were included. Median age of 72 (IQR 61-78) and 59% were
      male. The mean ischemic core volume was 27.6ml (SD 34.9ml). There were 235
      patients with an ischemic core volume of <70ml and 26 patients with an ischemic
      core volume of >=70ml. There was no statistically significant difference however
      in 90 day functional independence with 66% (154/235) in the <70ml core group and
      54% (14/26) in the >=70ml core group reaching a 90 day mRS<=2. CONCLUSIONS: We
      found that patients selected for ECR with ischemic core size >=70ml had clinical
      outcomes not significantly different compared with those with smaller ischemic
      cores. We recommend that large ischemic core size alone does not necessarily
      constitute an absolute contraindication for ECR. Randomized controlled studies
      are needed to better define the benefits for this group of patients. This article
      is protected by copyright. All rights reserved.

PMID- 30230697
TI  - A stable mesoporous metal-organic framework as highly efficient sorbent of
      dispersive micro solid-phase extraction for the determination of polycyclic
      aromatic hydrocarbons by HPLC.
AB  - Owing to the large molecular sizes of polycyclic aromatic hydrocarbons, their
      adsorption using microporous sorbents leads to a low adsorption capacity. Here,
      to increase the extraction capacity and detection sensitivity of polycyclic
      aromatic hydrocarbons, a highly efficient dispersive micro solid-phase extraction
      method was developed based on a stable mesoporous metal-organic framework named
      Jilin University China 48. Jilin University China 48 is a super hybrid with large
      one-dimensional hexagonal nanotube-like channels of 24.5 * 27.9 A, which exhibits
      high potential to be an efficient sorbent of dispersive micro solid-phase
      extraction to adsorb polycyclic aromatic hydrocarbons. By combining with high
      performance liquid chromatography, a sensitive method was developed for the
      determination of seven polycyclic aromatic hydrocarbons. The synthesized Jilin
      University China 48 exhibited excellent characteristics of stability, good
      morphology, large surface area, and open adsorption sites. Under the optimized
      extraction conditions, better extraction results were obtained than that of other
      methods reported previously. The proposed method exhibited high sensitivity with
      the limit of detections in the range of 0.021-0.13 ng/mL, good linearity in the
      range of 0.068-50 ng/mL with related coefficients of >0.9988, satisfactory
      precision with relative standard deviation of <4.3%, and adequate recoveries
      between 85.8 to 109.55% for all the target compounds.

PMID- 30230698
TI  - Chemical Composition, Security and Bioactivity of the Red Pigment from
      Penicillium purpurogenum Li-3.
AB  - The chemical composition, security and bioactivity of pigments from Penicillium
      purpurogenum Li-3 strain screened by our group were firstly studied in this work.
      DPPH and the filter disc diffusion method were used to determine the biological
      activities of the red pigments. The pigment was characterized by UV/VIS, FT-IR,
      NMR and UPLC-Q-TOF-MS. HPLC/MS was used to detect mycotoxins (citrinin) in
      fermentation broth. An acute toxicity was detected in the embryos of zebrafish.
      As a consequence, the crude red pigment from the AcOEt fraction showed better
      DPPH scavenge capacity and antibacterial activity. Spectroscopic (UV, FT-IR, 13 C
      NMR) and UPLC-Q-TOF-MS analysis revealed that the Penicillium purpurogenum Li-3
      red pigment (RPs) was monascus-like pigment and its molecular weight was
      439.1997. Moreover, the red pigment was shown to be weak cytotoxic against the
      zebrafish embryos. The yield of the red pigment increased 69 % under optimized
      culture conditions. These outstanding properties will enlarge the application of
      RPs for natural food additives, new antioxidant and antibacterial drug
      development.

PMID- 30230699
TI  - The efficacy and safety of ALK inhibitors in the treatment of ALK-positive non
      small cell lung cancer: A network meta-analysis.
AB  - PURPOSE: The current study was carried out to compare the effectiveness and
      safety of different ALK inhibitors in treating ALK+ NSCLC. METHODS: Progression
      free survival (PFS), disease control rate (DCR), overall response rate (ORR), and
      intracranial ORR and DCR have been aggregated to appraise the effectiveness of
      each ALKi. The discontinuation rate due to adverse events (AEs) was pooled to
      evaluate their safety. Bayesian network meta-analyses were used to compare the
      ORR, DCR, PFS, and discontinuation rate of patients treated with alectinib,
      ceritinib, crizotinib, and chemotherapy. RESULTS: Compared with chemotherapy, ALK
      inhibitors significantly prolonged PFS [hazard ratio (HR) and 95% confidence
      interval (CI): alectinib, 0.50 (0.43-0.58); ceritinib, 0.75 (0.69-0.83);
      crizotinib, 0.71 (0.66-0.76)]. The ORRs were significantly higher for ALK
      inhibitors than for chemotherapy [odds ratio (OR) and corresponding 95% CI:
      alectinib, 11.69 (4.29-36.56); ceritinib, 7.85 (3.44-19.27); crizotinib, 6.04
      (3.33-11.71)]. The discontinuation rates were lower for ALK inhibitors than for
      chemotherapy [OR and corresponding 95% CI: alectinib, 0.42 (0.12-1.36);
      ceritinib, 0.52 (0.20-1.35); crizotinib, 0.70 (0.30-1.62)]. CONCLUSIONS: ALK+
      NSCLC patients treated with ALKi tend to have longer PFS than those treated with
      chemotherapy. ALKi-naive patients tended to response better than their ALKi
      pretreated counterparts. Alectinib appeared to be preferable for treating brain
      metastases due to its high intracranial efficacy. Patients treated with alectinib
      or ceritinib tended to have higher ORR and DCR than patients with similar
      baselines treated with crizotinib or chemotherapy. No significant differences in
      discontinuation rate were found for alectinib, ceritinib, crizotinib, and
      chemotherapy.

PMID- 30230701
TI  - Corrigendum: Structure-Based Design of a Monosaccharide Ligand Targeting Galectin
      8.

PMID- 30230700
TI  - Behavioral predictors of improved speech output in minimally verbal children with
      autism.
AB  - We investigated the relationship between eight theoretically motivated behavioral
      variables and a spoken-language-related outcome measure, after 25 sessions of
      treatment for speech production in 38 minimally verbal children with autism.
      After removing potential predictors that were uncorrelated with the outcome
      variable, two remained. We used both complete-case and multiple-imputation
      analyses to address missing predictor data and performed linear regressions to
      identify significant predictors of change in percent syllables approximately
      correct after treatment. Baseline phonetic inventory (the number of English
      phonemes repeated correctly) was the most robust predictor of improvement. In the
      group of 17 participants with complete data, ADOS score also significantly
      predicted the outcome. In contrast to some earlier studies, nonverbal IQ,
      baseline levels of expressive language, and younger age did not significantly
      predict improvement. The present results are not only consistent with previous
      studies showing that verbal imitation and autism severity significantly predict
      spoken language outcomes in preschool-aged minimally verbal children with autism,
      but also extend these findings to older minimally verbal children with autism.
      Autism Res 2018, 11: 1356-1365. (c) 2018 International Society for Autism
      Research, Wiley Periodicals, Inc. LAY SUMMARY: We wished to understand what
      baseline factors predicted whether minimally verbal children with autism would
      improve after treatment for spoken language. The outcome measure was change in
      percentage (%) syllables approximately correct on a set of 30 two-syllable words
      or phrases. Fifteen were both practiced in treatment and tested; the remainder
      were not practiced in treatment, but only tested, to assess how well children
      were able to generalize their new skills to an untrained set of words. Potential
      predictors tested were sex, age, expressive language, phonetic inventory (the
      number of English speech sounds repeated correctly), autism severity, and
      nonverbal IQ. Phonetic inventory and (for some children) autism severity
      predicted children's posttreatment improvement. Nonverbal IQ and expressive
      language ability did not predict improvement, nor did younger age, suggesting
      that some older children with autism may be candidates for speech therapy.

PMID- 30230702
TI  - Improving the early screening procedure for autism spectrum disorder in young
      children: Experience from a community-based model in shanghai.
AB  - Most children with autism spectrum disorder (ASD) are not diagnosed until the age
      of 4, thus missing the opportunity for early intervention. The objective of this
      study was to investigate the feasibility of an early screening program for ASD
      applied during well-child visits in a community-based sample. The study lasted
      for 4 years and was divided into two stages. Stage I involved the implementation
      of the basic screening model in 2014. Toddlers received level 1 screening via
      section A of the Chinese-validated version of the Checklist for Autism in
      Toddlers (CHAT-23) during 18- and 24-month well-child visits in Xuhui District,
      Shanghai, China. Screen-positive children were referred to receive section B of
      the CHAT-23 for level 2 screening, and those still screen-positive were referred
      to undergo diagnosis and evaluation. Stage II involved the implementation of the
      improved screening model from 2015 to 2017 with the following modifications: (a)
      an added observational component in level 1 screening; (b) telephone follow-ups
      with the screen-positive families; and (c) dissemination of information on ASD to
      families. The results showed that 42 of 22,247 screened children were diagnosed
      with ASD. The ASD diagnosis rates were 0.1% in Stage I and 0.21% in Stage II. The
      screen-positive rate and the show rate of referral for level 1 screening
      increased by 76.92% and 58.43%, respectively, in Stage II compared to Stage I.
      Our results suggest that with appropriate logistic support, this two-level
      screening model is feasible and effective for the early screening of ASD during
      well-child visits. Autism Res 2018, 11: 1206-1217. (c) 2018 International Society
      for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Difficulty in the
      timely identification of autism spectrum disorder (ASD) results in missed
      opportunities for many ASD children to receive early intervention. In this study,
      we established an early screening model for ASD among children aged 18-24 months
      in the community by relying on the three-level child healthcare system in China.
      The results showed that this model can effectively identify and diagnose ASD in
      children at an early age and thus enable early intervention.

PMID- 30230705
TI  - Corrigendum.

PMID- 30230706
TI  - Erratum.

PMID- 30230707
TI  - How millennials could impact the evolution of wound care.

PMID- 30230708
TI  - Maternal pre-pregnancy weight and autistic-like traits among offspring in the
      general population.
AB  - : There is an emerging body of evidence demonstrating that maternal obesity at
      the time of conception increases the risk for Autism Spectrum Disorders (ASD)
      among offspring. We explored whether pre-pregnancy weight was related to autistic
      like traits among offspring not diagnosed with ASD. A large sample of women,
      recruited during the second trimester of pregnancy, had their height measured and
      reported their pre-pregnancy weight. These measurements were then converted to a
      Body Mass Index (BMI) using the formula: (weight in kilograms)/(height in metres2
      ). At 19-20 years of age, 1238 offspring of these women completed a measure of
      autistic-like traits, the Autism-Spectrum Quotient (AQ). Regression analyses
      identified a positive association between increasing maternal pre-pregnancy BMI
      and increasing AQ Total Score amongst offspring; this association was maintained
      even after controlling for a range of variables including maternal/obstetric
      factors (age at conception, education, smoking, alcohol consumption, hypertensive
      diseases, diabetes, threatened abortion), paternal BMI at pregnancy, and child
      factors (parity, sex) (P < .01, R2 =.03). Chi-square analyses found that women
      with pre-pregnancy obesity (BMI >= 30) were more likely to have offspring with
      high scores (>=26) on the AQ (P = .01). Follow-up binary logistic regression
      analyses also accounting for the same obstetric and sociodemographic variables
      found that the offspring of women with pre-pregnancy obesity were at a
      statistically significantly increased risk of having high scores (>=26) on the AQ
      (OR: 2.80; 95% CI: 1.06, 7.43). This study provides further evidence that
      maternal pre-pregnancy obesity is associated with autism-like behaviors in
      offspring. LAY SUMMARY: The current study explored whether pre-pregnancy weight
      was related to autistic-like traits among offspring not diagnosed with ASD. We
      found that pre-pregnancy body mass index in women is associated with the amount
      of autistic-like traits in their children in early adulthood. Specifically, women
      who were obese at the time of conception were more likely to have a child who had
      high levels of autistic-like traits in early adulthood.

PMID- 30230709
TI  - Bioengineering Organs for Blood Detoxification.
AB  - For patients with severe kidney or liver failure the best solution is currently
      organ transplantation. However, not all patients are eligible for transplantation
      and due to limited organ availability, most patients are currently treated with
      therapies using artificial kidney and artificial liver devices. These therapies,
      despite their relative success in preserving the patients' life, have important
      limitations since they can only replace part of the natural kidney or liver
      functions. As blood detoxification (and other functions) in these highly perfused
      organs is achieved by specialized cells, it seems relevant to review the
      approaches leading to bioengineered organs fulfilling most of the native organ
      functions. There, the culture of cells of specific phenotypes on adapted
      scaffolds that can be perfused takes place. In this review paper, first the
      functions of kidney and liver organs are briefly described. Then artificial
      kidney/liver devices, bioartificial kidney devices, and bioartificial liver
      devices are focused on, as well as biohybrid constructs obtained by
      decellularization and recellularization of animal organs. For all organs, a
      thorough overview of the literature is given and the perspectives for their
      application in the clinic are discussed.

PMID- 30230710
TI  - Prognostic value of metabolic tumour volume and total lesion glycolysis measured
      by 18F-fluorodeoxyglucose positron emission tomography/computed tomography in
      small cell lung cancer: A systematic review and meta-analysis.
AB  - INTRODUCTION: The aim of this study was to evaluate the prognostic value of
      metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for small cell
      lung cancer (SCLC). METHODS: MEDLINE, EMBASE and Cochrane Library databases were
      systematically searched. The pooled hazard ratio (HR) was used to measure the
      influence of MTV and TLG on survival. The subgroup analysis according to VALSG
      stage and the measured extent of MTV was performed. RESULTS: Patients with high
      MTV values experienced a significantly poorer prognosis with a HR of 2.42 (95% CI
      1.46-4.03) for overall survival (OS) and a HR of 2.78 (95% CI 1.39-5.53) for
      progression-free survival (PFS) from the random effect model, and the pooled HR
      from the fixed effect model was 2.10 (95% CI 1.77-2.50) for OS and 2.27 (95% CI
      1.83-2.81) for PFS. Patients with high TLG experienced a poorer prognosis with a
      HR of 1.61 (95% CI: 1.24-2.07) for OS from the random effect model, and the
      pooled HR from the fixed effect model was 1.64 (95% CI 1.37-1.96). Heterogeneity
      among studies was high for MTV in both OS and PFS meta-analyses (I2  = 87% and
      88% respectively). After removing one outlier study the heterogeneity was
      substantially reduced (I2  = 0%) and the pooled HR for the effect of MTV on OS
      was 1.80 (1.51-2.16, P < 0.00001), and on PFS it was 1.86 (1.49-2.33, P <
      0.00001), using either the fixed or random effects model. CONCLUSION: High MTV is
      associated with a significantly poorer prognosis OS and PFS, and high TLG is
      associated with a significantly poorer prognosis regarding OS for SCLC.

PMID- 30230711
TI  - Sliding behavior of zirconia porous implant surfaces against bone.
AB  - Different zirconia porous layers were produced on zirconia dense zirconia
      substrates by slip casting using powder with different mean sizes: 40 MUm (Z40),
      70 MUm (Z70), and 100 MUm (Z100). The dynamic and static coefficients of friction
      against bovine femoral bone, mimicking the implantation process, were conducted
      using a ball-on-flat reciprocating sliding tribometer under 3 N of normal load.
      Additionally, the porous layers were assessed with regard to their low
      temperature degradation (aging). Results revealed that the porous layers were
      able to keep their integrity during the sliding testes against bone, with no
      zirconia particles being transferred to the bone. Results did not show
      significant differences (p > 0.05) in kinetic and static COF values for Z40, Z70,
      Z100, and GRAD specimens, ranging from 0.53 to 0.77 and 0.65 to 0.90,
      respectively. The aging tests revealed that all surfaces were prone to low
      temperature degradation (~49% of monoclinic content after 18 h). In conclusion,
      the cohesive integrity of the layers and relatively high COF observed reveled
      that zirconia porous layers may be considered for replacing the current implant
      surfaces, and are expected to improve their primary stability. (c) 2018 Wiley
      Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018.

PMID- 30230712
TI  - Reproductive toxicology studies supporting the safety of molindone, a dopamine
      receptor antagonist.
AB  - BACKGROUND: An extended-release molindone (a dopamine D2 and serotonin
      antagonist) is currently being developed as a novel treatment for impulsive
      aggression (IA) in patients optimally treated for ADHD. Oral Good Laboratory
      Practice reproductive toxicology studies (fertility and early embryonic [FEE],
      prenatal/postnatal [PPN], embryo-fetal development [EFD]) were conducted with
      molindone HCl using International Conference on Harmonisation (ICH) S5(R2)
      compliant protocols. METHODS: In the FEE study, 0, 5, 15, or 30 mg kg-1  day-1
      was administered to female (2 weeks premating through implantation) and male (4
      weeks premating for 57 days) rats, and fertility parameters were evaluated. In
      the EFD studies, rats received 0, 5, 20, or 40 mg kg-1 day-1 on gestational days
      (GDs) 6-17; rabbits received 0, 5, 10, or 15 mg kg-1 day-1 on GDs 6-18.
      Ovarian/uterine and fetal parameters were evaluated at term. In the PPN study, F0
      rats received 0, 5, 20, or 40 mg kg-1 day-1 (GD6-LD21); behavior and reproduction
      were evaluated in F1 offspring. RESULTS: Parental hypoactivity and reduced body
      weight gain occurred in all studies. In the FEE, prolonged estrous cycles and
      delayed mating occurred at >=15 mg kg-1 day-1 , without effects on fertility or
      embryonic development. No developmental toxicity occurred in F1 fetuses. In F1
      pups, reduced preweaning growth was observed at 40 mg kg-1 day-1 , but there were
      no effects on postweaning growth, behavior, or reproduction. CONCLUSIONS:
      Molindone was not developmentally toxic in rats or rabbits at 69X and 6X clinical
      exposures, confirming the reproductive safety of molindone. Changes in estrous
      cyclicity were related to species-specific pharmacological effects of molindone
      in rodents and are not considered relevant to human risk.

PMID- 30230713
TI  - Acute molecular effects of pressure-controlled intermittent coronary sinus
      occlusion in patients with advanced heart failure.
AB  - AIMS: Cardiac repair has steered clinical attention and remains an unmet need,
      because available regenerative therapies lack robust mechanistic evidence.
      Pressure-controlled intermittent coronary sinus occlusion (PICSO), known to
      induce angiogenetic and vasoactive molecules as well as to reduce regional
      ischemia, may activate endogenous regenerative processes in failing myocardium.
      We aimed to investigate the effects of PICSO in patients with advanced heart
      failure undergoing cardiac resynchronization therapy. METHODS AND RESULTS: Eight
      out of 32 patients were treated with PICSO, and the remainder served as controls.
      After electrode testing including left ventricular leads, PICSO was performed for
      20 min. To test immediate molecular responses, in both patient groups, coronary
      venous blood samples were taken at baseline and after 20 min, the time required
      for the intervention. Sera were tested for microRNAs and growth factors. To test
      the ability of up-regulated soluble factors on cell proliferation and expression
      of transcription factors [e.g. Kruppel-like factor 4 (KLF-4)], sera were co
      cultured with human cardiomyocytes and fibroblasts. As compared with controls,
      significant differential expression (differences between pre-values and post
      values in relation to both patient cohorts) of microRNA patterns associated with
      cardiac development was observed with PICSO. Importantly, miR-143 (P < 0.048) and
      miR-145 (P < 0,047) increased, both targeting a network of transcription factors
      (including KLF-4) that promote differentiation and repress proliferation of
      vascular smooth muscle cells. Additionally, an increase of miR-19b (P < 0.019)
      known to alleviate endothelial cell apoptosis was found, whereas disadvantageous
      miR-320b (P < 0.023) suspect to impair expression of c-myc, normally provoking
      cell cycle re-entry in post-mitotic myocytes and miR-25 (P < 0.023), decreased, a
      target of anti-miR application to improve contractility in the failing heart. Co
      cultured post-PICSO sera significantly increased cellular proliferation both in
      fibroblasts (P < 0.001) and adult cardiomycytes (P < 0.004) sampled from a
      transplant recipient as compared with controls. Adult cardiomyocytes showed a
      seven-fold increase of the transcription factor KLF-4 protein when co-cultured
      with treated sera as compared with controls. CONCLUSIONS: Here, we show for the
      first time that PICSO, a trans-coronary sinus catheter intervention, is
      associated with an increase in morphogens secreted into cardiac veins, normally
      present during cardiac development, and a significant induction of cell
      proliferation. Present findings support the notion that epigenetic modifications,
      that is, haemodynamic stimuli on venous vascular cells, may reverse myocardial
      deterioration. Further investigations are needed to decipher the maze of complex
      interacting molecular pathways in failing myocardium and the potential role of
      PICSO to reinitiate developmental processes to prevent further myocardial decay
      eventually reaching clinical significance.

PMID- 30230714
TI  - Interaction of Non-polarizable Cations with Azaborine Isomers and Their Mono
      Substituted Derivatives: Position, Induction, and Non-Classical Effects Matter.
AB  - Progress in BN/CC isosterism has opened an overwhelming urge to find prospective
      applications of this class of materials. Herein, the interaction of three BN
      isosteres of benzene, i. e. 1,2-, 1,3-, 1,4-azaborines and their mono-substituted
      derivatives with Na+ and Mg2+ cations has been surveyed in light of symmetry
      adapted perturbation theory (SAPT) and interacting quantum atoms method (IQA). We
      have found that the orientation of the cations towards azaborines depends
      considerably on boron and nitrogen dispersion pattern. However, this tendency
      cannot be justified by electrostatics alone, without taking into account the
      induction as the major stabilizing factor, and Pauli repulsion, which effectively
      shapes the potential energy surface. Due to the significant role of induction,
      molecular electrostatic potentials (MEPs) can predict the interaction strength
      and anisotropy only if they are obtained from densities perturbed by the
      effective field of the cations. Through-bond and through-space effects of the
      substituents strongly depend on their position in the ring, where the through
      bond effects are dominated by the inductive contribution. The importance of the
      induction energy even at short distances, and of the non-classical IQA component
      signify the multi-center covalency character of azaborine-cation interactions.
      Therefore, a pure classical view on the interaction between the cation and
      compounds standing on the organic/inorganic border is to a large extent
      misleading.

PMID- 30230715
TI  - Spatial and temporal variations of childhood cancers: Literature review and
      contribution of the French national registry.
AB  - BACKGROUND: Significant increases in childhood cancer incidence since the 1970s
      have been consistently reported worldwide, but the persistence of the increase on
      recent periods is discussed. No conclusion can be drawn concerning the spatial
      variations of childhood cancer, either. This study is an in-depth investigation
      of the spatial and temporal variations of childhood cancer in France. An
      extensive review of all the studies published since 2000 on those issues is
      provided. METHODS: The study included 25 877 cases of childhood cancer registered
      nationwide over 2000-2014. The spatial heterogeneity (overdispersion,
      autocorrelation, overall heterogeneity) was tested, on two geographic scales, and
      two spatial scan methods were used to detect clusters of cases. The annual
      average percent change (AAPC) in incidence rate was estimated with Poisson
      regression models, and joinpoint analyses were considered. RESULTS: Glioma and
      non-Hodgkin lymphoma cases exhibited some spatial heterogeneity and two large
      clusters were detected. Overall, the incidence rate of childhood cancer was
      stable over 2000-2014 (AAPC = -0.1% [-0.3%; 0.2%]). A log-linear positive trend
      was significantly evidenced for gliomas other than pilocytic astrocytomas (AAPC =
      1.8% [0.9%; 2.7%]), with some suggestion of a leveling-off at the end of the
      period, while Burkitt lymphoma and germ cell tumor incidence rates decreased
      (AAPC = -2.2% [-3.8%; -0.5%] and AAPC = -1.9% [-3.4%; -0.3%], respectively). No
      spatial heterogeneity or significant time variation was evidenced for other
      cancers. CONCLUSION: Several types of childhood cancer displayed some spatial
      heterogeneity and two large clusters were detected, the origins of which are to
      be investigated and might include differences in case ascertainment. Overall, the
      results do not support a sustained increase in incidence rates of childhood
      cancer in recent years.

PMID- 30230716
TI  - Autocyclized and oxidized forms of SCR7 induce cancer cell death by inhibiting
      nonhomologous DNA end joining in a Ligase IV dependent manner.
AB  - Nonhomologous DNA end joining (NHEJ) is the major DNA double-strand break (DSB)
      repair pathway in mammals. Previously, we have described a small molecule
      inhibitor, SCR7, which can inhibit NHEJ in a Ligase IV-dependent manner.
      Administration of SCR7 within the cells resulted in the accumulation of DNA
      breaks, cell death, and inhibition of tumor growth in mice. In the present study,
      we report that parental SCR7, which is unstable, can be autocyclized into a
      stable form. Both parental SCR7 and cyclized SCR7 possess the same molecular
      weight (334.09) and molecular formula (C18 H14 N4 OS), whereas its oxidized form,
      SCR7-pyrazine, possesses a different molecular formula (C18 H12 N4 OS), molecular
      weight (332.07), and structure. While cyclized form of SCR7 showed robust
      inhibition of NHEJ in vitro, both forms exhibited efficient cytotoxicity.
      Cyclized and oxidized forms of SCR7 inhibited DNA end joining catalyzed by Ligase
      IV, whereas their impact was minimal on Ligase III, Ligase I, and T4 DNA Ligase
      mediated joining. Importantly, both forms inhibited V(D)J recombination, although
      the effect was more pronounced for SCR7-cyclized. Both forms blocked NHEJ in a
      Ligase IV-dependent manner leading to the accumulation of DSBs within the cells.
      Although cytotoxicity due to SCR7-cyclized was Ligase IV specific, the pyrazine
      form exhibited nonspecific cytotoxicity at higher concentrations in Ligase IV
      null cells. Finally, we demonstrate that both forms can potentiate the effect of
      radiation. Thus, we report that cyclized and oxidized forms of SCR7 can inhibit
      NHEJ in a Ligase IV-dependent manner, although SCR7-pyrazine is less specific to
      Ligase IV inside the cell.

PMID- 30230718
TI  - Top Standards Compliance Data Announced for 2016.

PMID- 30230719
TI  - New Alert Focuses on Safety Culture in Health Care.

PMID- 30230720
TI  - Understanding Key Changes to the Life Safety Standards.

PMID- 30230717
TI  - Descriptive epidemiology of cerebellar hypoplasia in the National Birth Defects
      Prevention Study.
AB  - BACKGROUND: Cerebellar hypoplasia is a rare disorder of cerebellar formation in
      which the cerebellum is not completely developed, smaller than it should be, or
      completely absent. The prevalence of cerebellar hypoplasia at birth is unknown,
      and little is known about epidemiological risk factors. Using data from the
      National Birth Defects Prevention Study (NBDPS), a population-based, case-control
      study, we analyzed clinical features and potential risk factors for nonsyndromic
      cerebellar hypoplasia. METHODS: The NBDPS included pregnancies with estimated
      delivery dates from 1997-2011. We described clinical features of cerebellar
      hypoplasia cases from the study area. We explored risk factors for cerebellar
      hypoplasia (case characteristics, demographics, pregnancy characteristics,
      maternal health conditions, maternal medication use, and maternal behavioral
      exposures) by comparing cases to non-malformed live born control infants. We
      calculated crude odds ratios (ORs) and 95% confidence intervals using logistic
      regression models. RESULTS: We identified 87 eligible cerebellar hypoplasia cases
      and 55 mothers who participated in the NBDPS. There were no differences in
      clinical features between interviewed and non-interviewed cases. Cerebellar
      hypoplasia cases were more likely than controls to be from a multiple pregnancy,
      be born preterm, and have low birth weight. Cerebellar hypoplasia cases were more
      likely to be born in or after 2005, as opposed to earlier in NBDPS. We found
      elevated ORs that were not statistically significant for maternal use of
      vasoactive medications, non-Hispanic black mothers, and mothers with a history of
      hypertension. CONCLUSIONS: Although unadjusted, our findings from a large,
      population-based study can contribute to new hypotheses regarding the etiology of
      cerebellar hypoplasia.

PMID- 30230721
TI  - Mississippi Telemedicine: Interviews with the Innovators.

PMID- 30230722
TI  - Top 10 Facts You Need to Know about Melanoma.

PMID- 30230723
TI  - Unusual Manifestations of NSAID Overdoses.

PMID- 30230724
TI  - Patient Health Information Breaches: What Now?.

PMID- 30230725
TI  - "Queen of GME" Reduces Hours but not Commitment.

PMID- 30230726
TI  - Michigan Licensing Board Members Have Immunity from Lawsuits.

PMID- 30230727
TI  - Making Accommodations for Hearing-impaired Employees.

PMID- 30230729
TI  - Top Tips to Protect Your Home against Seasonal Storms.

PMID- 30230728
TI  - Speaking Disparagingly about Minorities and LGBT Patients.

PMID- 30230730
TI  - Meet Dr. Michele Tulak-Gorecki An Interview with the MDA's 2017-18 President.

PMID- 30230731
TI  - Smoking Cessation Drugs: A Summary for Dental Professionals.
AB  - Currently, seven pharmaceutical products are approved by the United States Food
      and Drug Administration for smoking cessation. Five of these are nicotine
      replacement products. The remaining two are the non-nicotine containing
      medications varenicline and bupropion. This paper provides a summary of these
      smoking cessation pharmaceuticals for dental health professionals.

PMID- 30230732
TI  - The Flint Water Crisis: An Opportunity for Dentists to Help.

PMID- 30230733
TI  - Why Do We Prescribe Vicodin?.

PMID- 30230734
TI  - Fundamentals of Fluorescein Angiography.
AB  - In order to provide safe patient care during fluorescein angiography, it is
      critical that ophthalmic team members understand the use of fluorescein for
      diagnosing eye-related diseases and conditions, including appropriate doses for
      adult and pediatric patients. Awareness of side effects, adverse reactions, and
      complications of the contrast agent allow the ophthalmic health-care team to
      anticipate, respond quickly, and support the patient during and following the
      angiographic procedure using fluorescein.

PMID- 30230735
TI  - Glaucoma Diagnosis and Treatment: The Role of the Ophthalmic Nurse.
AB  - Glaucoma is one of the single largest causes of irreversible blindness.
      Glaucomatous vision loss is preventable with the appropriate diagnostic testing
      and treatment. Ophthalmic nurses play and important role in ensuring the success
      of glaucoma diagnosis and treatment.

PMID- 30230736
TI  - Improving Communication in the Ophthalmic Perioperative Setting.

PMID- 30230738
TI  - Certification vs. Registration or Licensing.

PMID- 30230737
TI  - Medical Marijuana and Glaucoma.

PMID- 30230739
TI  - DID YOU KNOW? What Direction Are You Heading? Horizontal Violence in the
      Workplace.

PMID- 30230740
TI  - New 2016 federal overtime compensation law possible this year: How Will This
      Affect Health Care Workers?

PMID- 30230741
TI  - IMPORTED MALARIA TO MAKKAH DISTRICT, SAUDI ARABIA: IS THERE ANY RISK OF LOCAL
      TRANSMISSION?
AB  - In Makkah, Saudi Arabia, there is an impending risk of imported malaria. This
      risk comes from the fact that millions of people, in majority from tropical and
      subtropical countries where malaria is endemic, visit the country to perform Hajj
      and Umrah every year. Moreover, millions of expatriates from endemic countries
      come to Makkah for work. Likewise, many Saudi citizens travel to endemic areas
      overseas for business and pleasure. We performed a retrospective analysis of all
      reported malaria cases in Makkah region, Saudi Arabia for years 2014 and 2015. In
      addition, sorting of mosquito populations in Makkah region was undertaken. Based
      on national data regarding reported malaria cases, 235 malaria cases were
      recorded in years 2014 and 2015. Of the reported cases 232 were non-Saudi and
      only 3 cases were Saudi. Those recorded Saudi cases were just returning from a
      travel to an endemic area. Most of the cases (79.6%) were P. falciprum and the
      remaining was P. vivax. Infected male represent 62% and female represent 38%. Age
      of the majority of reported cases (71.5%) lie between 31 and 50 years. Most of
      reported cases were from Chad, Pakistan, Nigeria and Sudan. Sorting of mosquito
      populations revealed the absence of malaria vectors in Makkah District.

PMID- 30230742
TI  - SEROPREVALENCE OF TOXOPLASMA GONDII INFECTION AND ITS AS- SOCIATED RISK FACTORS
      IN NEUROPSYCHIATRIC PATIENTS IN JAZAN PROVINCE, SAUDI ARABIA.
AB  - Toxoplasma gondii has worldwide distribution in nearly one-third of the human
      population. It is a neurotropic protozoan parasite so a potential role of T.
      gondii infection for some neuropsychiatric disorders was postulated. Patients
      with psychiatric disorders had high toxoplasmosis se- roprevalence. Limited
      information about toxoplasmosis seroprevalence in psychiatric patients was known
      in southern area of Saudi Arabia. The current cross sectional case control study
      aims at determination of the prevalence of T. gondii IgG & IgM in
      neuropsychiatric patients in Jazan Province. A total of 162 neuropsychiatric
      patients from Al-Amal hospital for psychiatric health and 162 subjects without
      neuropsychiatric manifestations from Jazan General Hospital, Jazan City, KSA.
      were enrolled in the study. Psychiatric diagnosis was based on the International
      Classification of Diseases-10 (ICD-10 classification). Serological analysis for
      latent toxoplasmosis (IgG) and active toxoplasmosis (IgM) was done using Enzyme
      Linked Immunosorbent Assay (ELISA). Investigations for the association with socio
      demographic, clinical and behavioral characteristics in psychiatric patients were
      also done. The serofrequency of IgG antibodies among neuropsychiatric patients
      was significantly higher than that of the controls (35.8% vs 14.8%) P = 0.0022.
      OR 3.2 with 95% CI= (1.4952 to 6.8774). However; serofrequency of toxoplasma IgM
      antibody between neuro-psychiatric patients and controls was not statistically
      significant (P > 0.05).,Bivariate and multivariate analysis for socio
      demographics and possible associated risk factors showed that contact to cats
      and/or dogs, eating under cooked meat, and contact to soil were significantly
      higher in neuropsychiatric patients than controls.

PMID- 30230743
TI  - ELECTRON MICROSCOPIC ASSAY OF BACTERIAL BIOFILM FORMED ON INDWELLING URETHRAL
      CATHETERS.
AB  - Biofilm formation on indwelling urinary catheters is a leading cause of Urinary
      tract infection (UTI). Presence of biofilm is associated with increased bacterial
      resistance to antimicrobial therapy and resultant treatment failure. The study
      detected a reliable method for diagnosis of biofilm formation by comparing
      scanning electron microscopy (SEM) and tissue culture plate method (TCP). The
      work was conducted on 20 urinary catheters from patients ranging from 1.5 to 85
      years with catheters that remained in situ for a period of 3 to 20 days. Samples
      of catheters for culture and SEM and samples of urine were taken at the same
      time. The correlation between renal conditions and biofilm formation was not
      significant (p=0.336). No significant correlation (p =0.836, 0.163 respectively)
      was found between predisposing conditions (DM, renal insufficiency, diarrhea and
      impaired immunity) and development of Catheter associated urinary tract infection
      ( CAUTI )and biofilm formation. Biofilm formation increased with duration of
      catheter in situ, but no significant.correlation was found (p=0.095). This could
      be due to small number of specimens. 9/20(45%) urine samples, 12/20(60%) catheter
      samples were positive by culture and 14/20(70%) catheters showed biofilm on SEM.
      4/12(33.33%) organisms isolated from catheter culture produced biofilm by TCP
      method. 9 isolates were recovered from 9 positive urine cultures. The
      microorganisms isolated were non Candida albicans (3/9), E. coli (2/9), C.
      albicans (2/9) and Acenitobacter (2/9). 14 isolates were recovered from 12
      culture- positive catheters. The organisms isolated were E.- coli (3/14), non
      Candida albicans (3/14), C. albicans (2/14), C tropicalis (2/14), Acenitobacter
      (2/14), Klebsiella (1/14) and Enterococcus (1/14). Reduction in microbial
      diversity with antimicrobial use was noticed but the correlation was
      insignificant (p=0.317). The correlation between urine culture results as well as
      catheter culture results and biofilm formation by SEM were both significant (p =
      0.008 & 0.000 respectively). The correlation between urine culture and TCP assay
      was insignificant (p =0.237). Using SEM as the gold standard method for the
      detection of biofilm, the sensitivity, specificity; total accuracy, PPV & NPV of
      urine culture and catheter culture were, 64.30%, 100%, 75%, 100%, 54% & 85.70%,
      100%, 90%, 100%, 75% respectively.

PMID- 30230745
TI  - PROTOZOA CAUSING FOOD POISONING.
AB  - Food poisoning also called foodbome illness, or illness caused by eating
      contaminated food is a term used to cover an unpleasant range of illnesses. Food
      poisoning symptoms vary with the source of contamination. Most types of food
      poisoning cause one or more of the following signs and symptoms: nausea,
      vomiting, watery diarrhea, abdominal pain and cramps and fever Signs and symptoms
      may start within hours after eating the contaminated food, or they may begin days
      or even weeks later. Sickness caused by food poisoning generally lasts from a few
      hours to several days.

PMID- 30230744
TI  - EPIDEMIOLOGICAL SITUATION OF URINARY SCHISTOSOMIASIS IN TAMWAH AREA, GIZA, EGYPT:
      ASSESSMENT AND CONTROL.
AB  - Preliminary studies were carried out on schistosomiasis in Giza Governorate for
      the last three years. These studies revealed that Tamwah village was one of areas
      afflicted by the highest number of Schistosoma haematobium infection cases. 'The
      study assessed the epidemiological situation of S. haematobium by parasitological
      and snail surveys. During April 2016, urine samples of 1285 children collected
      from three primary schools were centrifuged for microscopic examination. Also a
      snail survey was done along the shore (700m length). The snail were classified
      and examined for cercariae by light exposure and crushing. The results revealed
      that S. haematobiwn was 4.04% (52 cases). Majority were males (76.9% out of
      positive cases), with highly significant. There was a strong correlation between
      age of children and infection (44.2%) among oldest children (11 years) lowest
      (3.8%) was among the youngest group (6 years). Enterobius verinicularis ova in
      females' urine samples was 0.54% (7 cases). One was mixed infection with S.
      haematobium. The highest percentage among children infected with S. haematobium
      had pus cells 6- 30/HPF and RBCs less than 100/HPF in urine. There were crystals
      of uric acid, Ca oxalates and triple phosphate 5.8 %, 1.8% & 0.8% respectively.
      The snails were Lanistes carinatus, Bellamya unicolor, Physa micropleura,
      Succinia cleopatra, Cleopatra bulmnoides, Bulinus trancatus & Lymnaea natalensis.
      The commonest was B. trancatus followed by L. natalensis. Builinus spp. were
      positive for schistosomiasis -cercaria and Lymnaea spp were positive for
      virgulate xiphidiocercariae; parasites of bates, birds and amphibians.

PMID- 30230746
TI  - DIVERSITY AND COMPARATIVE STUDIES ON BULINUS SNAILS COLLECTED FROM TWO LOCALITIES
      IN EGYPT.
AB  - A comparative study of the shell structure, seasonal temperature and Calcium
      content of Bulinus snails from two areas (Damietta and Giza) in Egypt was done
      and compared with laboratory snails from Schistosome Biological Supply Center
      (SBSC). The shells of collected snails identified as Bulinus truncatus, showed a
      wide variation in shape. The results showed a significant differences were
      detected between the populations from SBSC and Damietta (p<0.05) for mean of
      measured shell width, aperture length, length of spire and number of whorls. The
      populations from Giza and Damietta governorates showed significant differences
      (P<0.05) in mean of measured length of diagonal, length of body whorl above
      aperture, length of spire and number of whorls. There were no statically
      significant differences between the populations from SBSC and Giza. The seasonal
      temperature affected on susceptibility of snails to infection with Schistosoma
      haematobium. The. mean prepatent period was short in summer and long in winter.
      The shells of S. haematobium - infected B. truncatus snails showed
      hypocalcifiction from all localities.

PMID- 30230747
TI  - CHITOSAN NANOPARTICLES PREPARED FROM LUCILIA CUPRINA MAGGOTS AS ANTIBACTERIAL
      AGENT.
AB  - Chitosan were prepared from cuticle of Lucilia cuprina maggots with two steps;
      deproteinization and deacetylation. It was characterized with solubility and
      Fourier Transform Infrared spectroscopy (FT-IR). Chitosan was ball-milled to
      obtain the chitosan nanoparticles which characterized with dynamic light
      scattering (DLS) and transmission electron microscope (TEM). Chitosan
      nanoparticles with degree of deacetylation (DDA) 80.5% were showed antibacterial
      activities against Klebsiella pneumoniae and Bacillus subtilis. The mode of
      action of chitosan nanoparticles on the tested bacteria was studied by TEM.
      Leakage of some cell contents, cell deformation and rupture of cell were
      observed, therefore, the chitosan nanoparticles were observed to be a powerful
      antibacterial agent.

PMID- 30230748
TI  - ZOONOTIC CUTANEOUS LESHMAIASIS THREE YEARS FEVER HOSPITAL RECORDS: WITH GENERAL
      DISCUSSION.
AB  - Leishmaniasis is widely present in more than 88 countries worldwide, resulting in
      up to 80,000 deaths annually. Leishmaniasis occurs as visceral, cutaneous, or
      mucocutaneous variants. Mucosal involvement can occur secondarily to the
      cutaneous or visceral varieties.

PMID- 30230749
TI  - INTESTINAL PARASITIC INFECTION IN EGYPTIAN CHILDREN: COULD IT BE A RISK FACTOR
      FOR IRON DEFICIENCY ANEMIA?.
AB  - A case control study that associates IDA with different parasitic infections and
      socioeconomic factors. The study enrolled 194 children with IDA and 180 age
      matched control. Patients diagnosed as IDA by complete blood count (CBC), and
      iron indices. All cases were subjected to complete history, anthropometric
      measures, and CBC and stool analysis. Ancylostoma duodenal, Ascaris lumbercoides
      and Giardia lamblia infections, lower family income, increased number of family
      members and eating meat in low frequency could be independent risk factors for
      IDA as detected by multivariate regression analysis. A. duodenale and G. lamblia
      were associated with lower ferritin levels in anemic patients. No significant
      associations as regards residence, body mass index, mother employment or
      education levels (p>0.05).

PMID- 30230750
TI  - MODIFIED CULTURE METHODOLOGY FOR SPECIFIC DETECTION OF BLASTOCYSTIS HOMINIS IN
      STOOL SAMPLES.
AB  - Blastocystis hominis provides major challenges for laboratory diagnosis due to
      its polymorphic nature in wet mounts which can result in confusion with other
      protozoa, yeast or even fat globules. Studies revealed that simple smears were
      less sensitive than in vitro cultivation using different media for the detection
      of B. hominis in stool specimens. Cultures of B. hominis are usually enriched by
      different types of sera to enhance growth and multiplication of the parasite. The
      aim of this study is to assess the use of two sera types other than horse serum
      that is commonly used in culture media for the growth, multiplication and
      detection of B. hominis in examined stool samples and comparing the results with
      those obtained using horse serum. Fifty stool samples were collected from
      patients suffering from different colonic manifestations attending Cairo
      University Hospitals. The samples were freshly cultured in three different
      culture media using horse serum (in Jones' medium), donkey serum (as a
      modification ii Jones' medium) and human plasma (in modified Pavlova's medium) in
      adequate preparations. Cultures were then left for incubation and examined by
      direct microscopy to detect Blastocystis hominis. The result showed of 50 stool
      samples studied,. 18 samples (36%) were positive results for B. hominis. The
      number of positive results obtained by horse serum, donkey serum and human plasma
      were 13,18and 11 respectively. Paired comparisons were made between each 2
      cultures with each culture set as a reference once to detect the most appropriate
      one for diagnosis When horse was set as the reference method, donkey serum showed
      a sensitivity of 100% and specificity of 86.5% with a 90% agreement between the 2
      methods. While human plasma showed a sensitivity of 46.2% and specificity of
      86.5% with an agreement of 76%. In addition, the vacuolar form was the commonest
      pattern observed in this study throughout all the three cultures.

PMID- 30230751
TI  - LIMIT OF MOLECULAR DETECTION OF STRONGYLOIDES STERCORALIS PARASITE PERFORMING.TWO
      PCR PROTOCOLS.
AB  - Low parasite density in chronic infection with S. stercoralis is a challenging
      diagnostic issue. Generally, molecular techniques don't depend on parasite
      viability while copro-culture or Baermann concentration method relies on the
      presence of living larvae in fecal samples. Therefore, evaluation of PCR-based
      methods is important to increase the detection rates in light or chronic
      infection. This study was designed to analyze the sensitivity of quantitative PCR
      (qPCR) and nested PCR (nPCR) regarding the minimum amount of S. stercoralis DNA
      template that can be reliably detected by each molecular technique. Strongyloides
      larvae were collected from cultured stool samples from suspected infected
      Egyptian children. After counting larvae present in a known volume under the
      microscope, DNA extraction was done and se- rial dilution of genomic materials
      was prepared. Then, qPCR and nPCR targeting the, small subunit of the rRNA gene
      were performed. Regarding qPCR, the limit of detection was 0.0005 S. stercoralis
      larvae/MUl, with crossing threshold (Ct) Value ranged from 17.8 to 38.7 while,
      nPCR did not detect from (0.002 to 0.0012 S tercopilis larvae/MUl) with minimum
      limit 0.004 S. stercoralis larvae/MUl. Real-time quantitative PCR is very
      sensitive technique that can detect very low genomic load up to about 10 (9.765)
      genome copies/reaction compared to. nested PCR which started positivity from
      78.125 genome copies/reaction. Therefore, qPCR is recommended to detect chronic
      strongyloidiasis especially in high-risk groups to prevent life- threatening
      spread of such infection.

PMID- 30230752
TI  - RESPONSE OF DOMINANT RODENTS TO COUMATETRALYL AND BROMADIOLONE IN GREATER CAIRO,
      EGYPT.
AB  - Since the 1950s, anticoagulant rodenticides are used to control rodents in public
      health and agriculture sectors. The extensive use of these compounds has acted as
      selective force to rodents, leading to resistance. Resistance mechanisms have
      been iden- tified in rats and mice, including the modification of the enzyme that
      activates vitamin K, vitamin K epoxide reductase (VKOR). Susceptibility levels of
      the Norway rat, Rattus norvegicus and the roof rat, Rattus rattus to
      coumatetralyl (first generation anticoagulant) and broamdiolone (second
      generation anticoagulant) by bioassay detection method under laboratory
      conditions were studied. Animals were trapped from Greater Cairo, Egypt in which
      the anticoagulant rodenticides were used to control rodents for long periods.
      Complete mortality was recorded for both species and sexes within the standard
      feeding periods (under no-choice feeding test for 6-days to coumatetralyl and 4
      days to bromadiolone). Rat species under studied still susceptible to
      coumatetralyl and bromadiolone. The present work revealed a significant
      correlation between species in comparison with consumed dose and death time. R.
      rattus showed more active ingredient intake (mg/kg) than R. norvegicus. Death
      time (days), R. rattus recorded higher mean values than R. norvegicus, also
      females showed higher mean values compared to males.

PMID- 30230753
TI  - ANTIMICROBIAL ACTIVITIES OF CHITOSAN NANOPARTICLES PREPARED-FROM LUCILA CUPRINA
      MAGGOTS (DIPTERA: CALLIPHORIDAE).
AB  - Chitosan nanoparticles Were studied as antimicrobial agent. The antibacterial
      activity of chitosan nanoparticles were investigated against three Gram-negative
      bacteria; Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi, and
      three Gram-positive bacteria; Staphylococcus aureus, Enterococcus faecalis and
      Streptococcus pyogenes. The 'antifungal activity were examined against three
      fungi; Geotrichum candidum, Candida krusei and Candida parapsilosis. The
      antiviral activities were tested against three viruses; Rift Valley Fever (RVFV),
      Herpes simplex-I (HSV-1) and Coxsackie viruses. Chitosan nanoparticles were
      inhibited all bacteria and fungi except E. faecalis seemed to be resistant
      strain. Infectivity titers of all viruses were reduced by chitosan nanoparticles,
      which are a natural antimicrobial agent.

PMID- 30230754
TI  - ZIKA VIRUS STRATEGIC RESPONSE FRAMEWORK FOR THE GULF STATES-2016: AN URGENT NEED
      FOR COLLABORATION.
AB  - The Zika virus (ZIKV) became the latest threat to global health security when WHO
      declared on 1t February 2016, that recently reported clusters of microcephaly and
      other neurological disorders in Brazil constitute a Public Health Emergency of
      International Concern (PHEIC). These clusters were reported concurrently with an
      outbreak of ZIKV, which has been ongoing in Brazil and other countries in the
      America region since 2015. A growing body of clinical and epidemiological data
      possibly leans towards a causal role for ZIKV as the occurrence of the clusters
      of microcephaly and other neurological disorders principally the Guillain-Barre'
      syndrome are associated in time and place with the ongoing ZIKV transmission in
      the America region. So far, Zika viral transmission has been documented in a
      total of 69 countries and territories with autochthonous transmission from 20I7
      to 10 August 2016. The geographical range of ZIKV has been increasing steadily.
      Consid'ring the presence of competent vectors that transmit ZIKV in, some parts
      of the Gulf countries, and the close relationship with Brazil, a local
      transmission of the virus is plausible once the virus is introduced through
      travel. This review suggests the integration of epidemiologicalind entomological
      surveillance for monitoring and control of the vectors of ZIKV. The risks
      associated with ZIKV infection and the possible threat to the Gulf States was
      described. A strategic Zika response framework (SRF) for the Gulf States has been
      developed to meet'their,urgent need for a collaborative and coordinated response
      for prevention and spread of ZIKV infection. A coordinated response of all
      partners in the Gulf States across sectors and services at national, as well as,
      regional levels is required.

PMID- 30230755
TI  - PARASITOLOGICAL STUDIES ON SOME INTESTINAL PARASITES IN PRIMARY SCHOOL CHILDREN
      IN ASWAN GOVERNORATE, EGYPT.
AB  - This cross sectional study in Aswan Governorate determined the prevalence of
      intestinal parasites and to identify the risk factors for infection in primary
      school children in this geographical area. The results would facilitate
      evaluation of the endemic level of different intestinal parasites and the
      determination of whether wiqespread or focal measures of parasite control are
      required. After obtaining official permission from the school administration,
      information and consent forms were given to the parents of all the
      schoolchildren. They were three-hundreds children aged between 6-12 year were
      enrolled; a detailed questionnaire, complete clinical assessment complete as well
      as stool analysis was done The study showed that the over-all infection was 31%,
      single parasitic infection was 26% and mixed one was 5%.The commonest helminthic
      infection was E. vermicularis 6.6% followed by H. nana 3% Ascaris lumbricoidesl%.
      The commonest protozoa infection was E. histolytica 8.3% followed by Giardia
      lamblia 3.7% and Cryptosporidium parvum 1.7%. Mixed infection was E.
      vernficularis plus E. histolytica (23.4%), E vermicularis plus G. lamblia
      (17.6%), E. vermicularis plus C. parvum (11.8%), E. histolytica plus H. nana
      (11.85%), A. -lumbricoides plus E. histolytica (17.6%) and G. lamblia plus E.
      histolytica in (11.8%). Parasitic infection was more prevalent in boys (53.8%)
      than girls (46.2%) and more prevalent in rural children (39.73%) than urban ones
      (20.13%) among age ranged from 6 to 12 years (8.97+/-1.72).

PMID- 30230757
TI  - THE PARASITIC PROFILE AMONG SCHOOL CHILDREN IN EI-WADI EL-GADDED GOVERNORATE,
      EGYPT.
AB  - Parasitic infection is still a serious public health problem in the world,
      especially in developing countries including Egypt. It represents a major cause
      of morbidity and mortality in childhood and among high-risk groups-in most parts
      of the world. This study detected the prevalence of parasitic infection among
      school children in-El-Wadi El-Gadded (the New Valley Governorate). A total of
      randomly chosen 1615 students aged from 6-16 years, (771 males & 844 female) from
      12 primary schools and 12 preparatory schools related to four centers (El
      Dakhala, El Farfra, Paris and Platt) from the New Valley. Governorate. Each child
      was subject to: A questionnaire sheet, Urine examination through sedimentation
      methods, Stool examination using: Direct smear, Simple sedimentation method and
      Modified Ziehl-Neelsen Stain, Blood samples were collected randomly from 450
      children and examined for Seropositivity of toxoplasmosis using (On
      SiteToxolgG/IgM Rapid Test- Cassette) and examination of hair & clothes for
      ectoparasites (lice). The overall prevalence of parasites was (39.1%) among
      primary and preparatory school children. The helminthes were E. vermicularis
      (15.2% & 17.1%); A. lumbricoides (1.3% & 1.9%) and then H. nana (0.9% & 0.6%) and
      the protozoa were E. histolytica (14.1% & 13.2%), Giardia lamblia (3.8% & 3.9%),
      and then Cryptosporidium parvum (0.09%) and seropositivity of toxoplasmosis was
      in (3.0% & 2.7%) among primary and preparatory school children respectively.
      Mixed infection was in (0.4%) among primary school children. Head lice
      infestaiion was more prevalent among primary school children than preparatory
      school ones with a ratio (3.5% &0.2%) respectively, was nil among males.

PMID- 30230756
TI  - PORTAL HYPERTENSION TREATMENT WITH CANDESARTAN PLUS PROPRANOLOL FOR NINE MONTHS
      RESTORES NORMAL PORTAL CIRCULATION HEMODYNAMIC PATTERN.
AB  - Post HCV liver cirrhosis is one of the most prominent etiologies behind the
      abnormal portal circulation hemodynamics. It occurs as a result of distorted
      balance between portal venous flow (PVF) and intrahepatic resistances (IHR). PVF
      is partially controlled by using both specific and non-specific beta blockers
      (NSBBs) that have insignificant effects on IHR. Angiotensin recep- tor blockers
      (ARBs) inhibit the activated hepatic stellate cell (HSC) contraction and thought
      to reduce the dynamic portion of IHR. The study aimed to slow down the venous
      blood flow and to reduce the IHR of portal vein vasculature to control sequelae
      of the enhanced post cirrhosis portal venous turbulence. We evaluated the effects
      of Candesartan plus propranolol compared to each of them individually in
      management of portal hypertension (PH). Three groups of 25 patients each,
      presented with chronic HCV infection and grade II- III esophageal varices (OV),
      were randomly assigned to one of three treatment regimens: Propranolol or
      Candesartan or both. Subjects were screened every three month by Doppler
      Ultrasound for a total of nine months. Damping Index(DI),,pu1se Pulsatiity Index
      (P), Portal Venous Flow (PVF) Volume, Portal Venous Peak Velocity (PVPV), and
      Portal Vein Diameter (PVD) were evaluated once every.third month. Our study
      concluded that combined therapy (Propranolol + Candesartan) induced highly
      significant improvements that led to restoration of normal values of DI, PI, PVF
      volume & PVPV overtime compared to monotherapy regimens (P>O.001). Data strongly
      recommended using Propranolol plus Candesartan' in overtime management of portal
      hypertension.

PMID- 30230758
TI  - AN OVERVIEW OF OSTEOMYELITIS WITH REFERENCE TO TREATMENT IN PARTICULAR MAGGOT
      DEBRIDEMENT THERAPY (MDT).
AB  - Osteomyelitis occurs either as a result of hematogenous seeding, contiguous
      spread of infection to bone from adjacent soft tissues and joints, or direct
      inoculation of infection into the bone as a result of trauma or surgery.
      Hematogenous'osteomyelitis is usually monomicrobial, while osteomyelitis due to
      contiguous spread or direct inoculation is, usually polymicrobial. Staphylococcus
      aureus, coagulase-negative staphylococci and aerobic grani-negative bacilli are
      the most common organisms; other pathogens including streptococci, enterococci,
      anaerobes, fungi and mycobacteria have also been implicated. Acute osteomyelitis
      typically presents with gradual onset of pain over several days. Local findings
      (tenderness, warmth, erythema and swelling) and systemic symptoms (fever, rigors)
      may. also be present. Chronic osteomyelitis tends to occur in the setting of
      previous osteomyelitis and presents with recurrent pain, erythema or swelling,
      sometimes in association with a draining sinus tract. Treatment of osteomyelitis
      often requires both surgical debridement of necrotic material and antimicrobial
      therapy for eradication of infection. The optimal duration of antibiotic therapy
      is not certain; but continuing parenteral antimicrobial therapy at least six
      weeks from the last debridement.. Maggot therapy is an effective and
      environmentally friendly treatment of complicated necrotic wounds that are
      resistant to conventional reatment and should also be considered in earlier.
      stages of treatment. The history of maggot therapy, and the mechanisms by which
      it works, is discussed..

PMID- 30230760
TI  - IMMUNOGENICITY ASSESSMENT FOR LUNG-STAGE AND BIOMPHALARIA ALEXANDRINA
      COCKTAIIVACCINE IN SCHISTOSOMA MANSONI INFECTED MICE.
AB  - : The availability of a new vaccine is usually needed as an additional component
      to chemotherapy for control of schistosomiasis. Different strategies of different
      types of vaccines were assessed to decrease morbidity but did not give the best
      protection. The study assessed the efficacy of BAAP, SLAP and their combined
      preparations together with BCG adjuvant as an effective anti-schistosomal
      vaccine. METHODOLOGY: Six groups of Swiss albino mice were used; (Gl) as a
      control, (G2) infected non immunized; (G3) infected and supported by Adj.; (G4)
      infected; vaccinated with BAAP and supported by Adj.; (G5) infected, vaccinated
      with SLAP and supported by Adj. and the target group (G6) infected, vaccinated
      with combined antigens (BAAP + SLAP) and supported by Adjuvant. Mice were
      sacrificed 8 weeks post infection for assessment the effect of our vaccine
      through parasitological, histopathological, serological and immunohisto- chemical
      study. The vaccination of mice with BAAP, SLAP and Adjuvant followed by challenge
      S. mansoni infection resulted in highest reduction percentages (92% & 86%) for
      mean numbers of adult burdens and fecal egg counts respectively,(82.4%, 81%) for
      granuloma number and diameter respectively compared with other groups. The
      improvement % of all measured enzymes was higher in G6 than other groups.IL1O was
      significantly increased in G6 than other groups; also, TNF was significantly
      decreased in G6 than other groups.

PMID- 30230759
TI  - COMPARISON OF IMMUNOCHROMATOGRAPHIC TEST AND MICROSCOPY IN THE DETECTION OF SOME
      ENTERIC PROTOZOA IN STOOL SAMPLES.
AB  - Infection with pathogenic intestinal protozoa. as Giardia lamblia,, Entamoeba
      histolytica and Cryptosporidium parvum cause considerable gastrointestinal
      morbidity, malnutrition and mortality worldwide, especially among young children
      in developing countries. The present study was carried out on 71 cases (44 males
      & 27 females) chosen from Pediatric and Internal Medicine Inpatient and
      Outpatient Clinics of Zagazig University Hospitals, complaining of different
      gastrointestinal troubles with an age range of 6-60 years. Also, 20 apparently
      healthy individuals (11 males & 9 females) cross matched were considered as a
      control negative group. All stool samples were examined by direct wet smears,
      concentration techniques, staining of the smears using trichrome stain and
      Modified Ziehl-Neelsen method. Copro-antigen detection in faecal sample was by
      using quick immunochromatographic test. A total of 71 cases suffering from
      different GIT manifestations showed G. lamblia (30.7%), Cryptosporidium parvum
      (19.8%), EntamoebahistolyticalE. dispar (11%) and mixed infection of three
      protozoa (6.6%). However, by copro-antigen G. lamblia was positive in (31.8%) of
      C. parvum in (20.9%); E. histolytica/E. dispar in (11%) of cases.
      Immunochromatography/copro-antigen test recorded sensitivity and spec- ificity of
      (100%) and (96.6%) respectively in G. lamblia detection. For C. parvum,
      sensitivity was (100%) and specificity was (97.1%) while for E. histolytica/E.
      dispar. sensitivity and specificity were (100%) for both. Immunochromatographic
      assay proved to be simple, easy and useful in confirming absence or the presence
      of intestinal protozoan infection in clinically suspected cases with negative
      stool examination.

PMID- 30230761
TI  - COMPARISON BETWEEN KATO-KATZ THICK SMEAR AND SEDIMENTATION TECHNIQUES IN
      DIAGNOSIS OF FAECAL-ORALLY TRANSMITTED HELMINTHES AND OTHER GEOHELMINTHES.
AB  - Kato-Katz technique is widely used for the diagnosis of Fecal-orally transmitted
      helminthic infections. It is relatively simple and inexpensive. However, a single
      slide prepared from a single stool specimen has low sensitivity, particularly in
      light infections. Therefore, there is a great need for concentration techniques.
      This study detected an accurate and affordable method for diagnosis of fecal
      orally transmitted helminthes and other geohelminthes. The study was carried out
      on 217 stool samples of different sex and age groups. Stool samples were
      collected from different urban and rural areas in Sharkia Governorate. Stool
      samples were examined macroscopically and analyzed by different parasitological
      techniques: direct wet mount (DWM), Kato-Katz thick smear, spontaneous
      sedimentation in tube technique (SSTT) and formol ether sedimentation technique
      (FEC). The results showed that formol ether sedimentation method detected 59
      positive samples followed by spontaneous sedimentation in tube technique (48/59
      positive samples). FEC showed significant difference when compared to direct wet
      mount and Kato-Katz thick smear. SSTT also showed significant difference when
      compared to DWM (P <0.05).The overall prevalence of intestinal helminthes was
      (29.6%) among studied samples in Sharkia Governorate. The commonest helminthic
      infection was H. nana (12%) followed by E. vemicularis(10%) then A. lumbricoides
      (3.7%).

PMID- 30230762
TI  - SPONDYLODISCITIS DESEASE EVALUATION IN PATIENTS WITH
      SERONEGATIVESPONDYLOARTHROPATHIES.
AB  - Spondylodiscitis (SD) is a destructive discovertebral lesion which is uncommon,
      but well recognised as a complication of Ankylosing Spondylitis (AS), and also
      called the Andersson lesion. This prospective study described 24 cases of AS, 12
      of them with SD with variable clinical presentation and radiological appearance
      (SD). Two had multiple lesions, in one patient spondylodiscitis was the
      presenting symptom of AS. None had a history of even a minor trauma and
      radiological appearance of Andersson lesion in AS. In a prospective analysis of
      24 patients with ankylosing spondylitis (AS) with multiple nationalities, 12
      individuals (50%) had spondylodiscitis, affecting the spine at various levels, we
      described the demographic data, full medical history, clinical examination and
      radiological findings including thoracolumbar spinal magnetic resonance imaging
      (MRI) in all patients diagnosed as SD with AS admitted to our department. All
      patients we're fulfilling the modified New York criteria and ASAS criteria. for
      AS. The results showed that the mean age of patients was 43 +/- 10.8 yrs, 16
      (66.667%) were males. Half of the 12 patients had multiple lesions (between two
      and six levels). Mean disease duration were 11+/-8.7. The most common site of
      lesion was the thoracic spine The prognosis was good with conservative treatment
      including NSAID's, rest, and physio- therapy. The literature was reviewed
      regarding the mechanisms that may contribute to these lesions: mainly
      inflammatory like increasing enthesopathy or mainly mechanical like
      pseudoarthrosis about a fracture site. It might be that both mechanisms could
      result in similar destructive intervertebral disc lesions.

PMID- 30230763
TI  - THE ANTIGENIC RELATIONSHIP BETWEEN SCHISTOSOMA MANSONI AND ITS INTERMEDIATE SNAIL
      HOST.
AB  - Schistosomiasis is a public health problem, in many developing: countries
      including Egypt, Determination of the antigenic relationship between S mansoni
      and its intermediate snail host (IMH) Biomphalaria alexandrina can open a new
      field for diagnosis and control of the dis- ease. In the present study infected
      and non-infected B. alexandrina foot and visceral hump tissue as well as S.
      mansion crude Ag (SWAg) were fractionated using SDS-PAGE. It's specific and cross
      reacted protein fractions were determine using EITB versus experimentally
      prepared mice hyper immune sera (HIS) versus each antigen. After treatment of
      fractionated S.mansoni crude worm antigens (SWAg) versus HIS produced after
      vaccination of mice by the same Ag, 8 kda protein fractions ranged from 35-140
      kda were reacted specifically. Treatment of fractionated B.alexandrina infected
      and non-infected foot and visceral hump Ag versus previous HIS revealed presence
      of common polypeptides bands between SWAg and non-infected snail antigens. The
      fraction at 135 kda, 68 kda, were detected in all cases, while that at 40-42 kda
      and that at 35 kda was diagnosed in SWAg and that of infected snails only. The
      fraction at 68 kda was reacted specifically between SWAg and all tested
      fractionated snail antigens either that of foot or visceral hump when they
      treated separately by HIS of mice vaccinated by each snail A eparately. The
      fraction at 135 kda was common between SWAg and snail (infected and non-infected)
      visceral hump antigen. The fraction at the level of 110 kda was diagnosed inSWAg,
      in non-infected foot antigen and visceral hump Ag. The fraction at the level of
      46-48 (da are common between SWAg and snail foot and visceral hump Ag after
      treated by HIS of mice vaccinated by foot Ag, Presence of common antigenic
      fractions between snail tissues and Schistosoma species can prefer an easily
      source of antigen valuable for diaguosis or vaccination as well as can be
      considered as new tool for determination to the snail IMH of new discovered
      trematode Darasites.

PMID- 30230764
TI  - CHARACTERIZATION OF THE HEMOCYTES OF SUSCEPTIBLE AND RESISTANT BIOMPHALARIA
      ALEXANDRINA SNAIL.
AB  - The internal defense system consists of soluble components of hemolymph and
      circulating cells known as hemocytes. The circulating hemocytes play a central
      role in innate immunity. This work aimed to study the hemocytes of both
      susceptible and resistant B. alexandrina snails exposed to S. mansoni infection
      using light and electron microscopes. Two tested groups were included in the
      study; 60 susceptible and 60 resistant B. alexandrina snails. Both tested groups
      were studied as regad the hemocyte count (before and after infection) and the
      morphological characteristics of both circulating and tissue hemocytes by light
      and electron microscopes. Before infection, .there was no significant difference
      between the two groups as regard the hemocyte count, however after infection,
      there is a significant decrease in the circulating hemocytes of the resistant
      group. Light microscopy revealed five morphological types of circulating cells of
      both susceptible and resistant snails. Regarding scannig electron microscopy,
      hemocytes of susceptible snails appeared rounded with smooth or slightly rough
      surface. However, that of the resistant snails appeared irregular in shaped with
      corrugated surface. Furthermore, Light microscopy and the transmission electron
      microscopy revealed signs of cell activation in the hemocytes of the resistant
      group. The circulating hemocytes consist of five cell types in both susceptible
      and resistant B. alexandarina and morphologies of these cells are quite similar,
      but with more signs of cell activations in the resistant group. More specific
      studies on the functional activities of the hemocytes and mechanisms that may
      affect or influence the susceptibility and/or non-susceptibility of molluscs to
      invade microorganisms is essential and how they can act in the immune response.

PMID- 30230765
TI  - ASSESSING THE EFFICACY OF NITAZOXANIDE IN TREATMENT OF CRYPTOSPORIDIOSIS USING
      PCR EXAMINATION.
AB  - Cryptosporidiosis is a gastrointestinal disease of humans and other animals,
      caused by the genus Cryptosporidium spp. It causes persistent diarrhea and
      malnutrition and is associated with increased mortality. This study aimed to
      assess the efficacy of nitazoxanide (NTZ) on clearing the oocysts of C. parvum
      among infected children using both parasitological and PCR techniques.120
      children (1-12y) shedding Cryptosporidium oocysts in their stools were enrolled
      in the study. They were classified on the basis of the immune status into
      immunocompetent (ICT) and immunocompromised (ICZ) groups. Each group were
      subdivided into two groups one of them received'NTZ, and the other received
      placebo. The efficacy of nitazoxanide was assessed clinically, parasitologically
      and by nested-PCR technique. At the end of 1st week of treatment, 80% of ICT/ NTZ
      group and 40% of ICT/ placebo group were free by PCR and 83.3% & 20% respectively
      were microscopically free. While at the end of 4th week, 93.3% of ICT/NTZ group
      and 43.3% of ICT/ placebo group were free by PCR and 96.7% & 26.7% respectively
      were microscopically free. Among the ICZ group, diarrhea was resolved in most
      patients receiving NTZ within 21 to 28 days of treatment initiation While, it
      resolved in the ICT group receiving NTZ in most patients within 3 to 5 days of
      treatment initiation.

PMID- 30230766
TI  - THE EFFECT OF STEM CELLS AS AN ADJUVANT ON THE IMMUNOGENICITY OF A POTENTIAL ANTI
      SCHISTOSOMAL VACCINE IN MICE.
AB  - Vaccination against schistosomes can be targeted towards the prevention of
      infection and/or to the reduction of parasite fecundity and pathology. However,
      as eggs are responsible mainly for schistosomiasis pathology, so crude soluble
      egg antigen (SEA) seems suitable to be used as a potential vaccine. Many studies
      have provided new insights establishing a role for mesenchymal stem cells (MSCs)
      in liver regeneration and improvement of schistosomiasis hepatic fibrosis, in
      addition to the need for standardized and effective adjuvant-vaccine
      formulations. So, the aim of this work is to evaluate the effect of stem cells
      when used as an adjuvant of a potential anti-schistosomal vaccine (crude SEA) in
      murine models. The current work was carried out on 100 mice (30 males for
      harvesting MSCs + 70 females for seven study groups, each of 10). A schedule of
      vaccination and challenge infection was followed so, GI (control healthy), G2
      (control infected only) infected subcutaneously with S. mansoni cercaria (80-90
      Schistosoma mansoni cercariae suspended in 0.2 ml distilled Water), G 3 (FCA then
      infected) received Freund's complete adjuvant (FCA) then infected, G4 (MSCs then
      infected) received MSCs then infected, G5 (SEA then infected) received SEA
      vaccine then infected, G6 (SEA+FCA then infected) received SEA vaccine and FCA
      then infected, G7 (SEA+MSCs then infected) received SEA vaccine and MSCs then
      infected. The current work was assessed by histopathological study and
      morphometric analysis (using H&E and Masson's Trichrome stains) to highlight
      number, size and type of liver granulomas and percentage of liver fibrosis,
      immunological and molecular studies (RNA extraction, Re- verse Transcriptase and
      PCR technique) for detection of interleukin-10 mRNA gene expression in liver
      tissue by reverse transcriptase & polymerase chain reaction (RT & PCR). The
      results showed that a- SEA alone as a potential anti-schistosomal vaccine was
      more or less moderately protective, b- MSCs alone before the infection had mild
      prophylactic effects, c- MSCs as an adjuvant of the crude SEA increased its
      capabilities with highly significant results regarding the decrease in granuloma
      number, size, percentage and density of hepatic fi- brosis, and d-There was
      significant increase in IL-10 mRNA gene expression on using (SEA+MSCs) (G7) if
      compared to other tested groups.

PMID- 30230767
TI  - DEVELOPMENT OF AN IN VITRO RNAI TO INVESTIGATE GENE FUNCTION IN BRUGIA MALAYI.
AB  - The RNA interference (RNAi) has the ability to turn off individual gene
      expression. So, it affords a remarkably specific tool for studying the effects of
      genes. It is regarded as a direct approach for determining such gene/genes
      functions and offers a valuable tool for modern drug discovery. The study aimed
      to develop in vitro RNAil in Brugia malayi with particular interest to study the
      function of Brugia malayi avr-14 (Bm-avr-14) and Brugia malayi f-tubulin (Bm-fi
      tubulin) genes. Bm-avr-14 is a gene encoding glutamate gated chloride channel
      (GluCl) which binds ivermectin and Bm-beta-tubulin is a gene encoding beta
      tubulin which binds albendazole. Adult female worms were soaked in heterogeneous
      short interfering RNA (hsiRNA) with interest to study the role of two genes Bm
      avr-14 and Bm-beta-tubulin. Then, we assessed the knock down effects of target
      genes using worminator system and real time PCR. We found that worms treated with
      hsiRNA of Bm-avr-14 had a significant reduction in microfilariae (mf) production
      in comparison with untreated worms or worms treated with hsiRNA of green
      fluorescent protein (GFP). No significant reduction in mf production with Bm-beta
      tubulin gene was obtained. There were no changes in the movement of adults
      treated with either Bm-avr-14 or Bm- beta-tubulin hsiRNAs. Inconsistent RNAi
      mediated suppression was achieved with Bm-avr-14 and Bm-beta- tubulin using real
      time PCR. The data may be helpful in assessment of drug target potential of
      genes.

PMID- 30230768
TI  - SERO-PREVALENCE OF ANTI- TOXOPLASMA GONDII ANTIBODIES AMONG PATIENTS WITH
      NEUROPSYCHIATRIC DISORDERS: EPILEPSY AND DEPRESSION.
AB  - Toxoplasma gondii infection is concerned to have an association with epilepsy and
      depression either as a cause or a potential risk factor for their occurrence.
      Nevertheless, there has been long-standing interest in investigating this
      possible association, the evidence for such relationship is yet not conclusive.
      The current study correlated between T. gondii infection and Neuropsychiatric
      disorders: epilepsy and depression, through serological valuation of anti
      Toxoplasma immunoglobulin (Ig) G antibodies. In the current study, 112 patients
      suffered from epilepsy (72 cryptogenic and 40 non-cryptogenic), 118 had
      depression and 60 healthy volunteers that had no history of any neuropsychiatric
      disorders in their first degree relatives were enrolled. Full history taking,
      complete physical examination, cranial magnetic resonance imaging (MRI), scalp
      electroencephalography (EEG), a structured questionnaire and T. gondii specific
      IgG antibody ELISA were performed to all groups. The results showed that the anti
      Toxoplasma IgG antibodies were detected among cases with cryptogenic epilepsy
      34.7% (25 out of 72 cases), non-cryptogenic epilepsy 2.5% (1 out of 40) and
      depression 20.3% (24 out of 118) groups compared to healthy. control group
      (11.7%). There were significant associations between T. gondii seropositivity of
      epilepsy and depression groups in age, residence, contact with pets and social
      class compared to control healthy group (p<0.05). Youth and adults had the
      highest sero-T. gondii infection especially male in rural areas with low social
      class.

PMID- 30230769
TI  - ?

PMID- 30230770
TI  - [Coordination meeting during psychiatric hospitalization : expectations,
      challenges and solutions].
AB  - Psychiatric treatments often involve numerous partners. The organization of
      coordination meetings during in-patient admissions is necessary in order to
      harmonize interventions. The expectations of each partner during such meetings
      may however differ and some issues that may seem important to some of them may be
      neglected. In this paper, we report the results of a survey conducted among the
      various partners involved in psychiatric patient's treatment in order to identify
      their expectations, the challenges they may have faced and the solutions they
      would propose. If perfection ca not be warrantied in all situations, taking these
      elements into account may improve these meetings and allow to better respect the
      role of each actor while giving to the patient the central role that they should
      play when defining their treatment.

PMID- 30230771
TI  - [Adverse effects of psychotropic drugs : when and how to talk to patients ?]
AB  - The way the potential adverse effects are presented during the introduction of a
      new medication in the context of psychiatric care can be decisive for subsequent
      care. This issue is approached from the testimonies of patients who have received
      multiple treatments over a long period of time and by several therapists. After
      describing the main adverse effects of psychotropic drugs, this article proposes
      a method to help patients documenting the adverse effects they experienced, in a
      way which should improve the dialogue with their therapists.

PMID- 30230772
TI  - [State of the art about credibility assessment of minors].
AB  - The issue of the credibility of a child's or adolescent's testimony in judicial
      sexual allegations has already been developed in many articles and books of the
      scientific literature. This article reports on the expert practices in the field
      of child psychology and legal psychiatry for credibility expertise in
      Switzerland. After illustrating the issues at stake in the analysis of various
      testimonies in the context of a recent trial (the Outreau case), we will describe
      the Statement Validity Analysis, a credibility assessment methodology recognized
      by the scientific literature and Swiss case law.

PMID- 30230773
TI  - [Evolution of customs and their impact on therapeutic demand].
AB  - The authors (a psychiatrist, and a pediatrician cum child psychiatrist, both
      family therapists) would like to share their thoughts about the increase in
      demand for therapeutic interventions in families reporting " problematic
      behaviour ", " reckless conduct ", or " disrespect of parental authority " in one
      or several of their children. The therapists have observed a shift in parental
      attitudes with respect to this type of behaviour. A clinical case will illustrate
      their statements. The authors then suggest some systemically oriented
      therapeutical options.

PMID- 30230774
TI  - [Negative symptoms in schizophrenia - overview and practical implications].
AB  - Negative symptoms in schizophrenia can be categorized in the symptom-dimensions
      of apathy (avolition, anhedonia and social withdrawal) and reduced expression
      (blunted affect and alogia). Based on the strong relevance for the quality of
      life and functional outcome during the course of an illness, a differentiated
      diagnostic and therapeutic approach is of high importance. Such a differentiation
      specifies primary negative symptoms (regarded as an integral part of
      schizophrenia) and secondary negative symptoms (regarded as a result of positive
      symptoms, comorbid depression, effects of antipsychotic medication, substance
      abuse or social deprivation). The following overview will summarize the various
      aspects of negative symptoms and discuss current diagnostic and therapeutic
      recommendations.

PMID- 30230775
TI  - [Intellectual disability: contribution of genetic studies to the etiological
      diagnosis].
AB  - The multidiscipinary care of patients with intellectual disability requires a
      structured and systematic etiological process. Today, advances in technology make
      it possible to perform diagnostic genetic analyzes that are highly contributive
      in this process. The CGH-array (Comparative Genomic Hybridization array) makes it
      possible to search for chromosomal anomalies with a very high level of
      resolution; high throughput sequencing can detect gene abnormalities on the whole
      exome or on a panel of genes. For the patient the detection of genetic anomalies
      aims to improve the quality of care; for related parties, genetic counseling is
      systematically offered.

PMID- 30230776
TI  - ?

PMID- 30230777
TI  - ?

PMID- 30230778
TI  - ?

PMID- 30230779
TI  - ?

PMID- 30230780
TI  - ?

PMID- 30230781
TI  - ?

PMID- 30230782
TI  - ?

PMID- 30230783
TI  - Serendipitous Signs, Symptoms, Laboratory Parameters, and Instrumental Patterns
      of Amniotic Fluid Embolism: Lessons from an Analysis of Case Reports.
AB  - Objective: Serendipitous Signs, Symptoms, Laboratory Parameters, and Instrumental
      Patterns of Amniotic Fluid Embolism: Lessons from an Analysis of Case Reports.
      Study Design: Wide analysis of the case reports on AFE published from 1990 to
      2014. A scoring system for quantifying the relevance was attributed to each sign,
      symptom, laboratory parameter, and instrumental abnormal pattern in AFE cases.
      Principal component rotated factor analysis was used to reduce data. The residual
      signs, symptoms, and laboratory and instrumental parameters were introduced in a
      multivariable logistic regression model (dependent variable: survival). Results:
      AFE, clinically, has at least 2 serendipitous symptoms (restlessness and
      confusion, at rates between 10-15%) and a serendipitous laboratory parameter
      (rise in C-reactive protein blood levels, between 2-3%). Fatal AFE cases relate
      mostly to the severity of cardiac and pulmonary impairment, rather than with
      restlessness, confusion, and rise in C-reactive protein. Conclusion: The
      hypothesis that AFE has atypical behavior should be retained; the extent to which
      serendipitous findings of AFE relate to AFE outcomes is uncertain.

PMID- 30230784
TI  - X-RAY SEMIOTICS OF ENDOCRINE OPHTHALMOPATHY. PART 2. THE OPTIC NERVE, LACRIMAL
      GLAND, SUPERIOR OPHTHALMIC VEIN.
AB  - Objective: to study the optic nerve, lacrimal gland, and superior ophthalmic vein
      in patients with different clinical forms of endocrine ophthalmopathy (EOP).
      Material and methods. 294 patients (559 orbits) with EOP were examined.
      Hydrodynamic disorders were detected in 43 patients. 46 patients (91 orbits) with
      mixed or myogenic types of edematous exophthalmos (EE) were diagnosed as having
      optic neuropathy (ON). Results and discussion. The paper presents the indicators
      of the optic nerve, lacrimal gland, and superior ophthalmic vein in patients with
      different clinical forms of EOP. This study provides evidence that ON in patients
      with EOP is characterized by specific changes in the optic nerve, as shown by
      computed tomography. It is ascertained that there are volumetric and structural
      changes in the lacrimal gland in 40.62% of the patients with mixed EE and in
      33.89% of those with myogenic EE. Conclusion. The study of the extraocular
      muscles in patients with ON-complicated EE may confirm that enlargement of the
      extraocular muscles at the orbital apex plays a major role in the pathogenesis of
      ON in this disease. The change in the anatomictopographic relationships of the
      orbit leads to compression of the superior ophthalmic vein, which entails
      obstruction of blood outflow from the orbit and causes ocular hypertension.

PMID- 30230785
TI  - NEW DIRECTIONS FOR IMPROVEMENT OF BREAST CANCER SCREENING.
AB  - Objective: to improve breast cancer diagnosis using an independent mammographic
      teleassessment by two radiologists. Material and methods. The results of a dual
      independent assessment of 3440 X-ray mammographic examinations were analyzed. The
      first assessment was made by a radiologist from a therapeutic-and-prophylactic
      establishment who had less than one year of practical experience in a mammography
      screening room. The second assessment was carried out by a radiologist with more
      than 5 years of experience from a specialized cancer institution. Results.
      According to the developed specialized interpretation software, recommendations
      and statistics for mammographic breast cancer screening, the investigators
      identified a group of 31 women who were recommended to be additionally examined
      at an oncology dispensary to verify the diagnosis of breast cancer. Eight of 17
      (47%) women with morphologically confirmed cancers after dual assessments of X
      ray mammographs were called again and referred to the oncology dispensary.
      Conclusion. Dual independent assessment of X-ray mammographs improved the
      diagnosis of BC with a maximum size of 1.5 cm or less, as well as that of
      malignant tumors manifesting as microcalcifications or imitating a benign
      process.

PMID- 30230786
TI  - Role of Proopiomelanocortin in Preventing Miscarriage.
AB  - Objective: To compare the distribution of proopiomelanocortin (POMC) in decidua
      and placenta samples from missed abortion and voluntary termination cases in
      order to research the effects in the etiology of missed abortion. Study Design:
      Decidual materials were collected from patients who were diagnosed with missed
      abortion (n=19) and legal voluntary termination cases (n=15) under 10 gestational
      weeks. Materials were divided into 2 groups for examination. For all samples,
      POMC primary antibody was performed by immunohistochemical staining. The number
      of stained cells was calculated by using the H-score technique. Results: In the
      missed abortion group the mean age was 28.7 (18-41), and in the control group the
      mean age was 27.5 (21-37). POMC immunoreactivity was determined to be lower in
      the parenchyma and placenta of the missed abortion group than those of the
      control group. POMC immunoreactivities were found to be higher in both the
      syncytiotrophoblast and cytotrophoblast cells of the missed abortion group than
      those of the control group (p<0.005). Conclusion: POMC has become a paradigmatic
      polypeptide precursor and has a role in the parturition process. Local production
      of POMC in placenta and decidua may influence pregnancy and may have a role in
      missed abortion pathogenesis.

PMID- 30230787
TI  - NEW APPROACH OF QUANTITATIVE NUCLEAR CARDIAC PERFUSION ASSESSMENT IN PATIENTS
      WITH PULMONARY HYPERTENSION.
AB  - Objective: to develop and implement a new processing approach of myocardial
      perfusion images obtained by single-photon emission computed tomography (SPECT)
      in patients with pulmonary hypertension (PH). Material and methods. 18 patients
      with idiopathic pulmonary hypertension underwent gated rest-stress perfusion
      SPECT with 99mTc-MIBI with CT-attenuation correction. Images were processed
      manually, with separate reorientation and semi-automatic contouring of both
      ventricles. MIBI intensity ratio in the right and left ventricles (RV/LV) was
      calculated using novel volumetric method, in comparison with other described
      approaches. Results. In patients with PH myocardial perfusion SPECT revealed
      abnormal RV visualization, dilation and reduced contractility, paradoxical motion
      and typical perfusion defects of interventricular septum. RV contouring in semi
      automatic mode was possible in 100% of cases. The average values of RV/LV ratio
      in PH patients and normal group was 0.6097 +/- 0.0090 and 0.2750 +/- 0.0355,
      respectively (p<0.001). Conclusion. The new method of quantitative calculation of
      perfusion impairments allows to reveal the features of myocardial perfusion of
      the right and left ventricles in patients with pulmonary hypertension, with the
      potential to assess therapy effectiveness in these patients.> <0.001).
      Conclusion. The new method of quantitative calculation of perfusion impairments
      allows to reveal the features of myocardial perfusion of the right and left
      ventricles in patients with pulmonary hypertension, with the potential to assess
      therapy effectiveness in these patients.

PMID- 30230788
TI  - CURRENT CAPABILITIES OF COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING FOR
      THE DETECTION OF COMPLICATIONS AFTER COMBINED PANCREAS AND KIDNEY
      TRANSPLANTATION.
AB  - Objective: to give computed tomography (CT)- and magnetic resonance imaging (MRI)
      based new anatomic-topographic relationships in patients after combined pancreas
      and kidney transplantation and to describe main visualization tasks and the types
      and frequency of various complications occurring in different periods after
      transplantation. Material and methods. Spiral CT and MRI images were analyzed in
      45 patients after pancreas and kidney transplantation. A total of 51 studies (35
      CTs and 16 MRIs) using intravenous contrast enhancement (n=34 (66%)) were
      performed. Results. A total of 55 complications, among which pancreatitis after
      pancreas transplantation was most common (55%), were found. Necrotizing
      pancreatitis following pancreas transplantation, which required open operative or
      percutaneous intervention, was diagnosed in 6.6%. Vascular complications were
      detected in 22%. Conclusion. The current capabilities of CT and MRI enable us to
      quickly obtain objective information on the status of transplanted organs, their
      vascular architectonics, as well as on the presence and type of occurred
      complications. Timely correction of identified complications positively affects
      the survival of transplanted organs and quality of life in a recipient.

PMID- 30230789
TI  - DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING IN THE DIAGNOSIS OF INTERVERTEBRAL
      DISC DEGENERATION IN THE LUMBOSACRAL SPINE.
AB  - Objective: to quantify the degree of degeneration of intervertebral discs (IVDs),
      by constructing functional diffusion-weighted imaging (DWI) maps, and to
      determine a correlation between the measured diffusion coefficient (DC) values
      and IVD changes on T1- and T2-weighted images. Material and methods. 545 IVDs
      were examined in 109 patients with no history of back pain syndrome and surgical
      spinal interventions. All the patients underwent magnetic resonance imaging of
      the lumbar spine; DWI maps were constructed and DC values estimated. Results.
      Statistically significant differences in the mean values of DC were determined
      for each of five IVDs. Multiple regression analysis showed that age and degree of
      degeneration were the most significant factors. The degree of IVD degeneration
      was negatively correlated with the values of DC at all levels (p<0.001). Also,
      there was a negative correlation between age and the value of DC at all levels
      (p<0.001). However, gender did not affect the value of DC (p>0.05), with the
      exception of L3-4. Conclusion. Age and the degree of degenerative changes in IVDs
      affect the value of DC. The value of DC is negatively correlated with the IVD
      degeneration graded by Pfirrmann and with the age of the examined patients. DW
      MRI can be used as a promising noninvasive method to diagnose the early stages of
      IVD degeneration.

PMID- 30230790
TI  - ASSESSMENT OF CEREBRAL PERFUSION IN PATIENTS WITH HEMODYNAMIC ISCHEMIC STROKE
      UNDERGOING RECONSTRUCTIVE BRACHIOCEPHALIC ARTERY INTERVENTIONS.
AB  - The paper deals with the assessment of cerebral perfusion in patients in the
      acute period of acute cerebrovascular accident before and after revascularization
      surgery. It gives a clinical example of using contrast-free perfusion magnetic
      resonance imaging (MRI) in a patient with hemodynamic ischemic stroke. The use of
      this technique made it possible to determine indications for early carotid
      endarterectomy for the contralateral internal carotid artery and to evaluate
      positive postoperative changes in cerebral perfusion and the patient's
      neurological status. The authors analyzed the current literature on this problem
      with a particular emphasis on the possibilities of using dynamic susceptibility
      contrast-enhanced and arterial spin-labeling contrast-free perfusion MRI in this
      category of patients. Carotid endarterectomy in the acute period of acute
      cerebrovascular accident can improve cerebral hemodynamics and the patient's
      neurological status and prevent recurrent cerebral circulatory disorders.
      Indications for this surgery should be determined by taking into consideration
      the results of perfusion MRI techniques (single-photon computed tomography
      contrastenhanced and contrast-free perfusion MRI).

PMID- 30230791
TI  - Impact of Cord Blood Adiponectin and Leptin Levels and Maternal Obesity on Birth
      Weight of Infants Born to Women with Gestational Diabetes Mellitus.
AB  - Objective: To evaluate the association between leptin level, adiponectin level,
      gestational weight gain, maternal constitutional factors, and the weights at
      birth and at 1 year of age in infants born to women with gestational diabetes
      mellitus (GDM). Study Design: Fifty-one women with GDM were recruited from June
      2011 to September 2011. Leptin and adiponectin levels in maternal and cord blood
      were measured and their correlations with infant's birth weight and weight after
      1 year were evaluated using Pearson correlation analysis. The weight correlations
      were also determined with maternal constitutional factors. Results: The neonatal
      birth weight positively correlates with cord blood leptin (r=0.316, p=0.024) and
      adiponectin (r=0.855, p=0.026) levels. One-year-old infant's weight correlates
      only with the cord blood adiponectin level (r=0.753, p=0.036). The infant's birth
      weight had positive correlations with maternal constitutional factors such as
      prepregnancy weight (r=0.340, p=0.015), prepregnancy BMI (r=0.289, p=0.040),
      prepartum weight (r=0.404, p=0.003), prepartum BMI (r=0.348, p=0.012), and
      gestational weight gain (r= 0.280, p=0.047). Conclusion: The infant's birth
      weight is closely associated with cord blood levels of both leptin and
      adiponectin and with pregravid and prepartum maternal obesity. The 1-year weight
      of infants born to GDM mothers is only associated with levels of adiponectin in
      cord blood.

PMID- 30230792
TI  - THE ROLE OF PREOPERATIVE BREAST MAGNETIC RESONANCE IMAGING IN PLANNING OF OPTIMUM
      SURGICAL TREATMENT FOR BREAST CANCER PATIENTS.
AB  - Breast cancer represents a global healthcare problem. In spite of all advances in
      treatment regimens for breast cancer, mortality from the disease stays high in
      countries where population based screening has not yet been introduced. On the
      other hand, there is a significant decrease in mortality from breast cancer in
      those countries where treatment is applied in an early phase of the disease, as a
      result of regular, population-based screening with mammography. Although
      mammography is the gold standard in diagnosing breast cancer in its early stage,
      it has limitations in detecting breast cancer sufficiently early in the dense
      portion of the breast. This calls for using the multimodality approach also for
      screening. In addition, the high frequency of multifocal and diffuse breast
      cancers calls for the need to describe the true extent of the disease
      preoperatively. The best modality to accomplish this goal is the use of magnetic
      resonance imaging of the breast (MRI). This report describes the role of breast
      MRI in the preoperative workup of the different subtypes of breast cancer.

PMID- 30230793
TI  - Heterotopic Triplet Pregnancy in Gonadotropin Stimulation Cycle: A Case Report.
AB  - Background: Heterotopic pregnancy is defined as the simultaneous presence of 2 or
      more pregnancies at different implantation sites, most commonly one intrauterine
      and one ectopic. Triplet heterotopic pregnancy refers to the presence of
      specifically 3 concurrent gestations with at least 1 being abnormally implanted.
      Heterotopic pregnancy is a potentially life-threatening condition that requires
      thorough diagnostic workup and prompt intervention. Case: We report the fourth
      case of triplet heterotopic pregnancy after ovarian stimulation with
      gonadotropins. A 24-year-old woman, G0, presented at 6 weeks of gestation with
      bilateral tubal ectopic pregnancies and a nonviable intrauterine pregnancy (IUP)
      after gonadotropin stimulation cycle. Bilateral tubal pregnancies were removed
      laparoscopically and the nonviable IUP via dilation and curettage. Conclusion:
      Although rare, heterotopic pregnancy of 2 or more gestations must be kept in mind
      when managing patients undergoing treatment with ART. Careful examination of
      bilateral adnexa and consideration of uterine sampling at the time of surgery for
      ectopic pregnancy is advisable, even for patients with few or no risk factors.

PMID- 30230794
TI  - Successful Closure of Small Iatrogenic Chorioamniotic Membranes Defect After
      Fetoscopy with Laser: A Case Report.
AB  - Background: Fetoscopic laser coagulation of the placental anastomoses is the
      standard treatment for twin-to-twin transfusion syndrome (TTTS). Despite certain
      improvements in fetoscopic technique, every fourth fetoscopic procedure is still
      complicated by preterm premature rupture of membranes, leading to ascending
      infection, fetal demise, and/or preterm delivery. re-TTTS occurs after fetoscopy
      in 2-14% of cases, impairing the outcome. Case: A 26-year-old woman underwent
      laser coagulation of placental anastomoses because of stage III TTTS at 21/6
      weeks of gestation. A microinvasive fetoscopic technique with 1-mm optic was
      used. Three weeks later, during a second fetoscopy because of re-TTTS, a defect
      of the chorioamniotic membranes of about 3 mm2 in area was visualized. This was
      without any signs of wound healing. We decided to perform laser coagulation with
      Nd:YAG laser of 10-30 W energy, moving from the wound's edge to the center until
      complete closure of the defect could be achieved. The patient gave birth at 34/0
      weeks to 2 healthy female infants weighing 2,013 g and 1,712 g. Microscopic
      evaluation of chorioamniotic membranes found dystrophic calcification within the
      treated membranes; this had been covered by amniotic epithelium. Conclusion:
      Small iatrogenic amniotic membrane defects could be successfully treated by laser
      technique.

PMID- 30230795
TI  - Term Delivery in a Woman with Severe Uterine Dehiscence After a Previous Cesarean
      Section: A Case Report.
AB  - Background: Cesarean section is the most frequently performed obstetrics
      operation. It can be associated with short- and long-term risks, one of which is
      uterine scar dehiscence. Women with uterine scar dehiscence often fear pregnancy
      because they are advised it may increase the risk of uterine rupture. It is
      generally recommended that women undergo transvaginal or laparoscopic repair of
      the uterine dehiscence before any future pregnancies. Case: A 32-year-old woman
      with a previous transverse lower-segment cesarean section complicated by severe
      uterine dehiscence, diagnosed by MRI before pregnancy, was treated with expectant
      management during a subsequent pregnancy. She was asymptomatic during pregnancy
      until term delivery with expectant management. Conclusion: We recommend that
      patients with severe uterine dehiscence undergo transvaginal or laparoscopic
      repair before attempting another pregnancy. However, if they become pregnant
      without repair of the dehiscence, they can be managed conservatively with routine
      surveillance and intermittent monitoring by ultrasound to term unless there is an
      emergency.

PMID- 30230796
TI  - Pretesticular and Testicular Effects of Systemic Sarcoidosis: A Case Report.
AB  - Background: Sarcoidosis is a multisystem inflammatory disease of unknown
      etiology. It is uncommon, with an incidence of approximately 16.5 per 100,000
      men.1 It is characterized by noncaseating epithelioid granulomata that typically
      affect the chest, skin, eyes, and, much less commonly, the genital system (<0.2%
      of cases). Sarcoidosis can affect any of the scrotal structures, although due to
      its rarity, investigation of solid masses of the testes are largely targeted
      towards excluding either a malignant or infective etiology.2 Case: We report a
      rare case of a 27-year-old male who presented with bilateral testicular and neck
      swellings. He underwent orchidectomy, and histopathology demonstrated
      sarcoidosis. He subsequently developed both pituitary and testicular sarcoidosis
      resulting in azoospermia. Through the administration of gonadotropins and
      surgical sperm retrieval we were able to retrieve sperm suitable for assisted
      reproductive technologies. Conclusion: This case illustrates the difficulties
      faced in managing the fertility of men who develop systemic sarcoidosis. It also
      highlights the diagnostic and therapeutic challenges faced by physicians when
      presented with a case of systemic sarcoidosis.

PMID- 30230798
TI  - Adrenal Mass Diagnosed in the Third Trimester of Pregnancy: A Case Report.

PMID- 30230799
TI  - Cesarean Section Revealing an Unsuspected Renal Angiomyolipoma in a Woman with
      Severe Hypertension During Pregnancy: A Case Report.
AB  - Background: Renal angiomyolipomas are uncommon during pregnancy, but it is
      important to consider them in the differential diagnosis, for the increased risk
      of complications such as bleeding, renal artery compression, and renovascular
      hypertension. Case: A 42-year-old woman was admitted at 34 weeks of gestation for
      severe abdominal pain in the right flank associated with severe hypertension.
      During the postadmission immediate cesarean section for fetal compromise,
      abdominal exploration revealed a massive retroperitoneal hematoma (around 30 cm)
      up to the cecal region until the lower edge of the liver. The diagnosis was the
      rupture of a renal angiomyolipoma causing renovascular hypertension. Conclusion:
      Renovascular hypertension should be considered in patients who present with
      accelerated hypertension, particularly if the hypertension is resistant to
      medical therapy and not associated with laboratory features of
      preeclampsia/eclampsia.

PMID- 30230800
TI  - Levonorgestrel-Releasing Intrauterine Contraceptive Device in the Peritoneal
      Cavity: A Report of Two Cases.
AB  - Background: In modern gynecology an intrauterine device (IUD) with levonorgestrel
      is often used as a method of contraception. The levonorgestrel-releasing
      intrauterine system is small and T-shaped. In Slovenia, only a gynecologist may
      insert it.  CASES: We present 2 clinical cases in which, despite strong evidence
      that no perforation had occurred during insertion, the IUD was found outside the
      uterus. If the IUD threads are not visible or the IUD cannot be located in the
      uterine cavity, an X-ray of the abdomen must be performed. If the IUD is found in
      the abdominal cavity outside the uterus, removal by laparoscopy is carried out.
      Conclusion: Given the large number of inserted IUDs, the complications associated
      with the levonorgestrel-releasing intrauterine system are quite rare, and
      therefore it remains one of the most widely used contraceptive methods.

PMID- 30230801
TI  - Letter to the Editor: Modified Posterior Perineoplasty in Women.

PMID- 30230802
TI  - Reply: Modified Posterior Perineoplasty in Women.

PMID- 30230803
TI  - [Early bucco-naso-sinus communication and shutter prosthetic treatment: About a
      clinical case].
AB  - The authors describe the early neglected oral communication of maxillary sinus
      and nasal cavity, causing reflux of liquid and sometimes solids through the nose,
      followed by immediate intrabuccal flow or posterior pharyngeal with fetidness.
      The objective of this work was to improve the therapy of immediate or delayed
      oral communication of maxillary sinus with nasal cavity and eventually and the
      quality of life.

PMID- 30230804
TI  - [Enlargement of mandibular canal and lower lip hypoesthesia revealing non
      Hodgkin's lymphoma of the mandible].
AB  - Introduction: Primary lymphoma of the mandible are rare and most often revealed
      by painless swelling. They are often confused with odontogenic lesions. Hence,
      their diagnosis is delayed. The authors report the case of an isolated mandibular
      lymphoma revealed by hypoesthesia of the lower lip and enlargement of the left
      mandibular canal. Case Report: A 35-year-old woman patient consulted for hemi
      mandibular pain with episodes of left labial hypoesthesia. Clinically, we noted
      the presence of a vestibular tumor in front of tooth 34. A panoramic radiograph
      revealed that the left mandibular canal was widely enlarged, extending from the
      mandibular foramen to the mental foramen. The biopsy revealed a B-cell lymphoma.
      No other localization was found. After treatment with seven courses of a
      chemotherapy based on R-CHOP followed by local radiotherapy, the patient was in
      remission eighteen months after treatment. Discussion: Primitive lymphoma of the
      mandible are rare; they represent about 0.6% of extra-nodal non-Hodgkin lymphoma.
      They occur at any age and mainly affect males. They most often come out as a
      painless swelling, sometimes ulcerated in the mouth. They are often misdiagnosed
      as a dental problem. Treatment combines variably radiotherapy and/or
      chemotherapy. The prognosis of bone lymphoma is more favorable than others
      malignancies bone, with a survival rate of 40-50% at five years.

PMID- 30230805
TI  - Undergraduate dental education in Nigeria: perceptions of dental students and
      recent dental graduates.
AB  - Background: Students' perception of their education is a subject that has
      received very little attention by those providing dental school education. This
      is more so in the Nigerian environment, where limited research has been carried
      out in dental education, particularly with respect to the students' perspectives
      on the quality of training received. Objective: Thus, the aim of this study was
      to determine the perceptions of dental students and recent dental graduates in
      Nigeria on their level of satisfaction with the quality of academic and clinical
      training received in their respective dental schools and the challenges faced in
      receiving this training. Methods: This was a cross-sectional descriptive study
      carried out amongst 271 dental students and recent dental graduates from eight
      dental schools in the country. Ethical approval for the study was obtained from
      the Institutional Review Board of the Lagos University Teaching Hospital (LUTH).
      Data collection was via self-administered questionnaires. Statistical analysis
      was carried out using SPSS 17. Results: The final study sample was made up of 239
      students, with a mean age of 24.57 (2.21) years. The two dental specialties in
      which the least level of satisfaction was recorded with regard to the quality of
      academic training received were Conservative Dentistry and Orthodontics, while
      for clinical training they were Conservative Dentistry and Oral
      Biology/Pathology. The three most common factors which were adversely affecting
      the quality of clinical training received were, poor electricity supply,
      insufficient dental chairs and quality of training received. Conclusion: Dental
      students and recent graduates of Nigerian Dental schools are not satisfied with
      the quality of undergraduate training received in some dental specialties at
      their respective dental schools.

PMID- 30230806
TI  - ECMO for Severe Acute Respiratory Distress Syndrome.

PMID- 30230807
TI  - Multifunctional Scaffolds with Improved Antimicrobial Properties and
      Osteogenicity Based on Piezoelectric Electrospun Fibers Decorated with Bioactive
      Composite Microcapsules.
AB  - The incorporation of bioactive compounds onto polymer fibrous scaffolds with
      further control of drug release kinetics is essential to improve the
      functionality of scaffolds for personalized drug therapy and regenerative
      medicine. In this study, polymer and hybrid microcapsules were prepared and used
      as drug carriers, which are further deposited onto polymer microfiber scaffolds
      [polycaprolactone (PCL), poly(3-hydroxybutyrate) (PHB), and PHB doping with the
      conductive polyaniline (PANi) of 2 wt % (PHB-PANi)]. The number of immobilized
      microcapsules decreased with increase in their zeta-potential due to
      electrostatic repulsion with the negatively charged fiber surface, depending on
      the polymer used for the scaffold's fabrication. Additionally, the immobilization
      of the capsules in dynamic mechanical conditions at a frequency of 10 Hz resulted
      in an increase in the number of the capsules on the fibers with increase in the
      scaffold piezoelectric response in the order PCL < PHB < PHB-PANi, depending on
      the chemical composition of the capsules. The immobilization of microcapsules
      loaded with different bioactive molecules onto the scaffold surface enabled
      multimodal triggering by physical (ultrasound, laser radiation) and biological
      (enzymatic treatment) stimuli, providing controllable release of the cargo from
      scaffolds. Importantly, the microcapsules immobilized onto the surface of the
      scaffolds did not influence the cell growth, viability, and cell proliferation on
      the scaffolds. Moreover, the attachment of human mesenchymal stem cells (hMSCs)
      on the scaffolds revealed that the PHB and PHB-PANi scaffolds promoted adhesion
      of hMSCs compared to that of the PCL scaffolds. Two bioactive compounds,
      antibiotic ceftriaxone sodium (CS) and osteogenic factor dexamethasone (DEXA),
      were chosen to load the microcapsules and demonstrate the antimicrobial
      properties and osteogenesis of the scaffolds. The modified scaffolds had
      prolonged release of CS or DEXA, which provided an improved antimicrobial effect,
      as well as enhanced osteogenic differentiation and mineralization of the
      scaffolds modified with capsules compared to that of individual scaffolds soaked
      in CS solution or incubated in an osteogenic medium. Thus, the immobilization of
      microcapsules provides a simple, convenient way to incorporate bioactive
      compounds onto polymer scaffolds, which makes these multimodal materials suitable
      for personalized drug therapy and bone tissue engineering.

PMID- 30230808
TI  - Induction of Oxidative Stress and Cell Death in Neural Cells by Silica
      Nanoparticles.
AB  - Silica nanoparticles (SiNPs) are produced on an industrial scale and used in
      various fields including health care, because silica is stable, inexpensive, and
      easy to handle. Despite these benefits, there is concern that exposure to SiNPs
      may lead to adverse effects in certain types of cells or tissues, such as
      hemolysis, immune responses, and developmental abnormalities in the brain and
      developing embryos. Although investigations on the toxicity of SiNPs against
      neurons are essential for medicinal use, only a few studies have assessed the
      direct effects of SiNPs on cells derived from the central nervous system. In this
      study, we investigated the toxic effects of SiNPs on primary cultures of
      hippocampal cells, using SiNPs with diameters of 10-1500 nm. We showed that
      treatment with SiNPs caused oxidative stress and cell death. Furthermore, we
      found that these cytotoxicities were dependent on the particle size,
      concentration, and surface charge of SiNPs, as well as the treatment temperature.
      The toxicity was reduced by SiNP surface functionalization or protein coating and
      by pretreating cells with an antioxidant, suggesting that contact-induced
      oxidative stress may be partially responsible for SiNP-induced cell death. These
      data will be valuable for utilizing SiNPs in biomedical applications.

PMID- 30230809
TI  - Untemplated Resveratrol-Mediated Polydopamine Nanocapsule Formation.
AB  - Nanocapsules can be designed for applications including drug delivery, catalysis,
      and biological imaging. The mussel-inspired material polydopamine is a promising
      shell layer for nanocapsules because of its free radical scavenging capacity,
      ability to react with a broad range of functional molecules, lack of toxicity,
      and biodegradability. Previous reports of polydopamine nanocapsule formation have
      relied on a templating approach. Herein, we report a template-free approach to
      polydopamine nanocapsule formation in the presence of resveratrol, a naturally
      occurring anti-inflammatory and antioxidant compound found in red wine and
      grapes. Synthesis of nanocapsules occurs spontaneously in an ethanolic
      resveratrol/dopamine.HCl solution at pH 8.5. UV-vis absorbance spectroscopy and X
      ray photoelectron spectroscopy indicate that resveratrol is incorporated into the
      nanocapsules. We also observed the formation of a soluble fluorescent dopamine
      resveratrol adduct during synthesis, which was identified by high-performance
      liquid chromatography, UV-vis spectroscopy, and electrospray ionization mass
      spectrometry. Using transmission electron microscopy and dynamic light
      scattering, we studied the influence of solvent composition, dopamine
      concentration, and resveratrol/dopamine ratio on the nanocapsule diameter and
      shell thickness. The resulting nanocapsules have excellent free radical
      scavenging activity as measured by a 2,2-diphenyl-1-picrylhydrazyl radical
      scavenging assay. Our work provides a convenient pathway by which resveratrol,
      and possibly other hydrophobic bioactive compounds, may be encapsulated within
      polydopamine nanocapsules.

PMID- 30230810
TI  - Disentangling the Role of Surface Chemical Interactions on Interfacial Charge
      Transport at BiVO4 Photoanodes.
AB  - Chemical transformations that occur on photoactive materials, such as
      photoelectrochemical water splitting, are strongly influenced by the surface
      properties as well as by the surrounding environment. Herein, we elucidate the
      effects of oxygen and water surface adsorption on band alignment, interfacial
      charge transfer, and charge-carrier transport by using complementary Kelvin probe
      measurements and photoconductive atomic force microscopy on bismuth vanadate. By
      observing variations in surface potential, we show that adsorbed oxygen acts as
      an electron-trap state at the surface of bismuth vanadate, whereas adsorbed water
      results in formation of a dipole layer without inducing interfacial charge
      transfer. The apparent change of trap state density under dry or humid nitrogen,
      as well as under oxygen-rich atmosphere, proves that surface adsorbates influence
      charge-carrier transport properties in the material. The finding that oxygen
      introduces electronically active states on the surface of bismuth vanadate may
      have important implications for understanding functional characteristics of water
      splitting photoanodes, devising strategies to passivate interfacial trap states,
      and elucidating important couplings between energetics and charge transport in
      reaction environments.

PMID- 30230811
TI  - Fast-Response Flexible Photochromic Gels for Self-Erasing Rewritable Media and
      Colorimetric Oxygen Indicator Applications.
AB  - Photoreversible color switching that can change colors with fast response and
      high stability is urgently desired in color-on-demand applications. Yet,
      developing such materials has long been a significant challenge. In this work, a
      strategy based on the integration of TiO2 nanoparticle (NP) photocatalytic color
      switching of redox dyes and poly(vinyl alcohol) gel matrix could produce robust
      and flexible photochromic gels (FPGs) that exhibit fast light-responsive time and
      high photoreversible stability. Benefited by the soft network structures and
      monomeric form of redox dyes in the FPG maintained by poly(vinyl alcohol) and
      ethylene glycol molecules, as well as enhanced photoreductive activity of TiO2
      NPs modified by both surface ligands and oxygen vacancies, the FPG exhibits long
      photoreversible switching cycles (>=50 times), decoloration in a short period of
      less than 8 s upon UV illumination, and recoloration in 16 min in ambient air and
      rapidly in 140 s upon near-infrared light illumination. Consequently, the
      excellent photoreversible color switching of the FPGs is highly applicable as
      both self-erasing rewritable media and colorimetric oxygen indicators. We believe
      that the current systems represent a big step forward toward practical
      applications, such as time-sensitive information storage, colorimetric oxygen
      sensor, and potentially many other technologies.

PMID- 30230812
TI  - Enhancement of Out-of-Plane Charge Transport in a Vertically Stacked Two
      Dimensional Heterostructure Using Point Defects.
AB  - Point defects in 2D materials block in-plane charge transport, which incurs
      negative effects on the photoresponse of 2D monolayer materials. In contrast to
      in-plane charge transport, we show that out-of-plane charge transport in 2D
      materials can be enhanced through controllable formation of point defects, thus
      enhancing the photoresponse of a vertical heterostructure. Graphene and WSe2
      monolayers were stacked together to construct a vertical heterostructure (W/G).
      Se point defects were artificially formed on the top atomic layer of WSe2 with
      controllable density via Ga ion irradiation. The interlayer charge transport in
      the W/G heterostructure was detected with femtosecond optical probe-pump
      measurements and photoelectric detection. Our experiments show that point defects
      can be used to provide higher transfer rate for out-of-plane charge transport and
      more electronic states for photoexcitation, leading to enhanced photoinduced
      interlayer charge transfer from WSe2 to graphene. Based on this feature, a
      photodetector based on W/G modified by point defects is proposed and implemented,
      exhibiting a fast photoresponsivity (~0.6 ms) (2 orders of magnitude larger than
      the photoresponse in pristine W/G). This work demonstrates that out-of-plane
      charge transport is enhanced by the presence of point defects and illustrates an
      efficient method to optimize the performance of photoelectric devices based on
      vertical heterostructures.

PMID- 30230813
TI  - SuFEx in Metal-Organic Frameworks: Versatile Postsynthetic Modification Tool.
AB  - A new type of click reaction, sulfur(VI) fluoride exchange (SuFEx), has been
      utilized to prepare five postsynthetically modified UiO-67 series metal-organic
      frameworks (MOFs). The postsynthetic modification (PSM) via SuFEx can be achieved
      selectively for the sulfonyl fluoride (R-SO2F) without degrading the MOF
      structure as confirmed by X-ray crystallographic analysis. The present SuFEx
      method provides a straightforward tool for introducing new functionality inside
      MOFs. Introduction of an imidazolium group into the MOF afforded a heterogeneous
      catalyst for the benzoin condensation reaction.

PMID- 30230814
TI  - Metabolic Labeling of Pseudaminic Acid-Containing Glycans on Bacterial Surfaces.
AB  - The rise in antibiotic-resistant bacteria is causing worldwide concerns. The
      urgent need for new antibacterial drugs calls for new thinking and strategies to
      explore novel, narrow-spectrum, and pathogen-specific antibacterial targets.
      Legionaminic acid (Leg) and pseudaminic acid (Pse) are nonulosonic acid
      carbohydrates with structural similarity to eukaryotic sialic acid, and are
      distributed in numerous pathogenic Gram-negative bacteria as components of cell
      surface-associated glycans. They are involved in the host interaction,
      pathogenicity, antiphage defense mechanism, and immune escape mechanism. To
      further explore their biological significance, we developed a synthesis of 2
      acetamido-4-azidoacetamido-2,4,6-trideoxy-l-altrose (Alt-4NAz) and 2
      azidoacetamido-4-acetamido-2,4,6-trideoxy-l-altrose (Alt-2NAz), among which Alt
      4NAz served as an effective chemical reporter to realize bacterial Pse metabolic
      labeling. The effectiveness of this chemical reporter has been demonstrated in
      Pseudomonas aeruginosa, Vibrio vulnificus, and Acinetobacter baumannii strains.
      Expectedly, this strategy can provide a useful assay to detect phenotypic
      presence of Pse biosynthesis and screen for agents targeting this pathway.

PMID- 30230815
TI  - Photocatalysis in Two-Dimensional Black Phosphorus: The Roles of Many-Body
      Effects.
AB  - Two-dimensional (2D) black phosphorus (BP) has drawn tremendous attention in
      solar-light-driven catalytic processes for its intriguing chemical and physical
      properties. Benefiting from the highly anisotropic electronic structure induced
      by its puckered crystal geometry, 2D BP tends to have greater confinement with
      respect to traditional inorganic nanomaterials, thereby leading to robust many
      body effects. Such Coulomb-interaction-mediated effects dominate the electronic
      and optical properties of 2D BP-based nanosystems, where exotic correlations
      between photoinduced species give rise to unique photoexcitation processes that
      are closely associated with the involved photocatalytic behavior. In this
      Perspective, we highlight the critical role of many-body effects in 2D BP-based
      photocatalysis and exemplify the relationships between the correlated
      photoinduced species-dominated photoexcitation processes and photocatalytic
      behavior involved therein. The relevant challenges and opportunities in pursuing
      efficient 2D BP-based solar energy utilization are also discussed.

PMID- 30230817
TI  - Surface-Enhanced Raman Scattering Based Microfluidics for Single-Cell Analysis.
AB  - The integration of surface-enhanced Raman scattering (SERS) with droplet
      microfluidics has the potential to improve our understanding of cellular systems.
      Herein, we present the first application of SERS droplet microfluidics for single
      cell analysis. A microfluidic device was used to encapsulate single prostate
      cancer cells and wheat germ agglutin (WGA)-functionalized SERS nanoprobes in
      water-in-oil droplets that were subsequently locked into a storage droplet array
      for spectroscopic investigation. The stationary droplets enabled the rapid
      identification of SERS regions of interest in live cancer cells by allowing
      collection of "fast" coarse maps over an area of several square millimeters
      followed by "slower" detailed interrogation of the identified hotspots. We
      demonstrate SERS at cellular resolution via a proof-of-concept assay that detects
      glycan expression on the surface of prostate cancer cells using WGA-modified
      metallic nanoparticles. The data illustrates the potential of SERS optofluidic
      systems for high-throughput cell screening and illustrates a previously
      unobserved high degree of cell-to-cell variability in the size and number of
      glycan islands.

PMID- 30230816
TI  - Automated Plasma Glycomics with Linkage-Specific Sialic Acid Esterification and
      Ultrahigh Resolution MS.
AB  - High-throughput mass spectrometry (MS) glycomics is an emerging field driven by
      technological advancements including sample preparation and data processing.
      Previously, we reported an automated protocol for the analysis of N-glycans
      released from plasma proteins that included sialic acid derivatization with
      linkage-specificity, namely, ethylation of alpha2,6-linked sialic acid residues
      and lactone formation of alpha2,3-linked sialic acids. In the current study, each
      step in this protocol was further optimized. Method improvements included
      minimizing the extent of side-reaction during derivatization, an adjusted glycan
      purification strategy and mass analysis of the released N-glycans by ultrahigh
      resolution matrix-assisted laser desorption/ionization Fourier transform ion
      cyclotron resonance MS. The latter resolved peak overlap and simplified spectral
      alignment due to high mass measurement precision. Moreover, this resulted in more
      confident glycan assignments and improved signal-to-noise for low-abundant
      species. The performance of the protocol renders high-throughput applications
      feasible in the exciting field of clinical glycomics.

PMID- 30230818
TI  - Structure-Stability-Function Mechanistic Links in the Anti-Measles Virus Action
      of Tocopherol-Derivatized Peptide Nanoparticles.
AB  - Measles remains one of the leading causes of child mortality worldwide and is re
      emerging in some countries due to poor vaccine coverage, concomitant with
      importation of measles virus (MV) from endemic areas. The lack of specific
      chemotherapy contributes to negative outcomes, especially in infants or
      immunodeficient individuals. Fusion inhibitor peptides derived from the MV Fusion
      protein C-terminal Heptad Repeat (HRC) targeting MV envelope fusion glycoproteins
      block infection at the stage of entry into host cells, thus preventing viral
      multiplication. To improve efficacy of such entry inhibitors, we have modified a
      HRC peptide inhibitor by introducing properties of self-assembly into
      nanoparticles (NP) and higher affinity for both viral and cell membranes.
      Modification of the peptide consisted of covalent grafting with tocopherol to
      increase amphipathicity and lipophilicity (HRC5). One additional peptide
      inhibitor consisting of a peptide dimer grafted to tocopherol was also used
      (HRC6). Spectroscopic, imaging, and simulation techniques were used to
      characterize the NP and explore the molecular basis for their antiviral efficacy.
      HRC5 forms micellar stable NP while HRC6 aggregates into amorphous, loose,
      unstable NP. Interpeptide cluster bridging governs NP assembly into dynamic
      metastable states. The results are consistent with the conclusion that the
      improved efficacy of HRC6 relative to HRC5 can be attributed to NP instability,
      which leads to more extensive partition to target membranes and binding to viral
      target proteins.

PMID- 30230819
TI  - Coupled Kinetics of Ferrihydrite Transformation and As(V) Sequestration under the
      Effect of Humic Acids: A Mechanistic and Quantitative Study.
AB  - In natural environments, kinetics of As(V) sequestration/release is usually
      coupled with dynamic Fe mineral transformation, which is further influenced by
      the presence of natural organic matter (NOM). Previous work mainly focused on the
      interactions between As(V) and Fe minerals. However, there is a lack of both
      mechanistic and quantitative understanding on the coupled kinetic processes in
      the As(V)-Fe mineral-NOM system. In this study, we investigated the effect of
      humic acids (HA) on the coupled kinetics of ferrihydrite transformation into
      hematite/goethite and sequestration of As(V) on Fe minerals. Time-resolved As(V)
      and HA interactions with Fe minerals during the kinetic processes were studied
      using aberration-corrected scanning transmission electron microscopy, chemical
      extractions, stirred-flow kinetic experiments, and X-ray absorption spectroscopy.
      Based on the experimental results, we developed a mechanistic kinetics model for
      As(V) fate during Fe mineral transformation. Our results demonstrated that the
      rates of As(V) speciation changes within Fe minerals were coupled with
      ferrihydrite transformation rates, and the overall reactions were slowed down by
      the presence of HA that sorbed on Fe minerals. Our kinetics model is able to
      account for variations of Fe mineral compositions, solution chemistry, and As(V)
      speciation, which has significant environmental implications for predicting As(V)
      behavior in the environment.

PMID- 30230820
TI  - What Goes Up Must Come Down: Integrating Air and Water Quality Monitoring for
      Nutrients.
AB  - Excess nitrogen and phosphorus ("nutrients") loadings continue to affect
      ecosystem function and human health across the U.S. Our ability to connect
      atmospheric inputs of nutrients to aquatic end points remains limited due to
      uncoupled air and water quality monitoring. Where connections exist, the
      information provides insights about source apportionment, trends, risk to
      sensitive ecosystems, and efficacy of pollution reduction efforts. We examine
      several issues driving the need for better integrated monitoring, including:
      coastal eutrophication, urban hotspots of deposition, a shift from oxidized to
      reduced nitrogen deposition, and the disappearance of pristine lakes. Successful
      coordination requires consistent data reporting; collocating deposition and water
      quality monitoring; improving phosphorus deposition measurements; and filling
      coverage gaps in urban corridors, agricultural areas, undeveloped watersheds, and
      coastal zones.

PMID- 30230821
TI  - Conformation and Aggregation of Selectively PEGylated and Lipidated Gastric
      Peptide Hormone Human PYY3-36.
AB  - The gastric peptide hormone human PYY3-36 is a target for the development of
      therapeutics, especially for treatment of obesity. The conformation and
      aggregation behavior of PEGylated and lipidated derivatives of this peptide are
      examined using a combination of fluorescence dye assays, circular dichroism (CD)
      spectroscopy, analytical ultracentrifugation (AUC) measurements, small-angle X
      ray scattering (SAXS) and cryogenic-transmission electron microscopy (cryo-TEM).
      The behavior of two PYY3-36 derivatives lipidated (with octyl chains) in
      different positions is compared to that of two derivatives with PEG attached at
      different residues and to that of the native peptide. We find that, unexpectedly,
      PYY3-36 forms amyloid fibril structures above a critical aggregation
      concentration. Formation of these structures is suppressed by PEGylation or
      lipidation. PEGylation significantly reduces the (reversible) loss of alpha-helix
      content observed on heating PYY3-36. The PEG conjugates form mainly monomeric
      structures in solution- coiled-coil formation, and other aggregation presumably
      being sterically hindered by swollen PEG chains. However, some small aggregates
      are detected by AUC. In complete contrast, both of the two lipidated peptides
      show the formation of spherical micelle-like structures which are small
      oligomeric aggregates. Our findings show that PEGylation and lipidation are
      complementary strategies to tune the conformation and aggregation of the
      important gastric peptide hormone human PYY3-36.

PMID- 30230822
TI  - Blue Emitting Single Crystalline Assembly of Metal Halide Clusters.
AB  - The rich chemistry of organic-inorganic metal halide hybrids has enabled the
      development of a variety of crystalline structures with controlled morphological
      and molecular dimensionalities. Here we report for the first time a single
      crystalline assembly of metal halide clusters, (C9NH20)7(PbCl4)Pb3Cl11, in which
      lead chloride tetrahedrons (PbCl42-) and face-sharing lead chloride trimer
      clusters (Pb3Cl115-) cocrystallize with organic cations (C9NH20+) to form a
      periodical zero-dimensional (0D) structure at the molecular level. Blue light
      emission peaked at 470 nm with a photoluminescence quantum efficiency (PLQE) of
      around 83% was realized for this single crystalline hybrid material, which is
      attributed to the individual lead chloride clusters. Our discovery of single
      crystalline assembly of metal halide clusters paves a new path to functional
      cluster assemblies with highly tunable structures and remarkable properties.

PMID- 30230824
TI  - New in Silico Trends in Food Toxicology.
AB  - Ever growing numbers of chemicals in food and drinking water make it impossible
      to address safety by classical approaches in toxicology. In silico chemical
      methods could be a first-line for hazard characterization, requiring food
      toxicology to expand the use of approaches currently well applied in medicinal
      chemistry.

PMID- 30230823
TI  - Dicationic Ionic Liquids of Herbicide 2,4-Dichlorophenoxyacetic Acid with Reduced
      Negative Effects on Environment.
AB  - Due to high volatility and water solubility, 2,4-dichlorophenoxyacetic acid (2,4
      D) can easily enter into the atmosphere and water bodies by volatilization,
      drift, leaching, or runoff, which results in potential threats to the environment
      and human health. The physicochemical properties of pesticides can be regulated
      by preparing their ionic liquids. In this work, a series of dicationic ionic
      liquids (DILs) of 2,4-D were prepared to reduce its environmental risk and
      enhance herbicidal activity. The solubility, octanol-water partition coefficient,
      surface tension, and volatilization rate results of DILs showed that these
      properties could be optimized by choosing appropriate countercations. Compared to
      2,4-D ammonium salt, DILs have lower volatility, water solubility, and surface
      tension as well as higher lipophilicity. Benefiting from optimized
      physicochemical properties, DILs HIL8-12 exhibited better herbicidal activity
      against three typical broadleaf weeds than 2,4-D ammonium salt, and their fresh
      weight inhibition rates increased by 2.74-46.84%. The safety assessment
      experiment indicated that DILs were safer to wheat than commercialized forms of
      2,4-D. The DILs could reduce the environmental risk of 2,4-D caused by high
      volatility and water solubility and would be potential alternatives to its
      commercialized formulations.

PMID- 30230828
TI  - Synthesis and in Vitro Bioactivity of Polyunsaturated Fatty Acid Conjugates of
      Combretastatin A-4.
AB  - Combretastatin A-4 (CA-4) (1) is a plant-derived anticancer agent binding to the
      tubulin colchicine site. Polyunsaturated fatty acids (PUFAs) are readily taken up
      by cancer cells and have been used to improve cell targeting. In the present
      study, four CA-4-PUFA conjugates were synthesized by coupling combretastatin A-4
      (1) with several polyunsaturated fatty acids. The conjugates (2a-d) were
      characterized using spectroscopic methods. Their cytotoxicity was evaluated
      against human breast cancer cells (MCF-7), and the inhibition of tubulin
      polymerization was determined in vitro. All conjugates influenced tubulin
      polymerization, with the arachidonic acid conjugate (2c) displaying cytotoxicity
      similar in potency to the natural product CA-4 (1).

PMID- 30230825
TI  - Plant Sr Isotope Ratios As Affected by the Sr Isotope Ratio of the Soil and of
      the External Sr Inputs.
AB  - The 87Sr/86Sr ratio of a produce is generally linked with the soil geological
      features of the growing areas. This study aimed at assessing to which extent the
      addition of external Sr by agricultural practices, like irrigation and mineral
      nutrient supply, influences this relationship. In a first experiment, oat plants
      in two soils reflected the 87Sr/86Sr of the soil. However, this link was
      significantly altered at increasing levels of external Sr soil supplies. In a
      second experiment, apple trees transplanted in pots modified their original
      87Sr/86Sr, which became progressively closer to the soil Sr isotope ratio. The
      addition of tap water and fertilizers, with different Sr isotopic signatures,
      slightly affected plant 87Sr/86Sr. Results confirm the potential of the 87Sr/86Sr
      ratio as a geographical tracer of agricultural commodities, but whenever the
      range of 87Sr/86Sr variability among soils from different geographical areas is
      narrow, the influence of external Sr-sources may smooth over these diversities.

PMID- 30230827
TI  - In Vivo Selectivity and Localization of Reactive Oxygen Species (ROS) Induction
      by Osmium Anticancer Complexes That Circumvent Platinum Resistance.
AB  - Platinum drugs are widely used for cancer treatment. Other precious metals are
      promising, but their clinical progress depends on achieving different mechanisms
      of action to overcome Pt-resistance. Here, we evaluate 13 organo-Os complexes: 16
      electron sulfonyl-diamine catalysts [(eta6-arene)Os( N, N')], and 18-electron
      phenylazopyridine complexes [(eta6-arene)Os( N, N')Cl/I]+ (arene = p-cymene,
      biphenyl, or terphenyl). Their antiproliferative activity does not depend on p21
      or p53 status, unlike cisplatin, and their selective potency toward cancer cells
      involves the generation of reactive oxygen species. Evidence of such a mechanism
      of action has been found both in vitro and in vivo. This work appears to provide
      the first study of osmium complexes in the zebrafish model, which has been shown
      to closely model toxicity in humans. A fluorescent osmium complex, derived from a
      lead compound, was employed to confirm internalization of the complex, visualize
      in vivo distribution, and confirm colocalization with reactive oxygen species
      generated in zebrafish.

PMID- 30230829
TI  - Catalysis of Thiol-Thioester Exchange by Water-Soluble Alkyldiselenols Applied to
      the Synthesis of Peptide Thioesters and SEA-Mediated Ligation.
AB  - N-Alkyl bis(2-selanylethyl)amines catalyze the synthesis of peptide thioesters or
      peptide ligation from bis(2-sulfanylethyl)amido (SEA) peptides. These catalysts
      are generated in situ by reduction of the corresponding cyclic diselenides by
      tris(2-carboxyethyl)phosphine. They are particularly efficient at pH 4.0 by
      accelerating the thiol-thioester exchange processes, which are otherwise rate
      limiting at this pH. By promoting SEA-mediated reactions at mildly acidic pH,
      they facilitate the synthesis of complex peptides such as cyclic O-acyl
      isopeptides that are otherwise hardly accessible.

PMID- 30230830
TI  - Understanding the Behavior of the Above-Room-Temperature Molecular Ferroelectric
      5,6-Dichloro-2-methylbenzimidazole Using Symmetry Adapted Distortion Mode
      Analysis.
AB  - The exploitable properties of many functional materials are intimately linked
      with symmetry-changing phase transitions. These include properties such as
      ferroelectricity, second harmonic generation, conductivity, magnetism and many
      others. We describe a new symmetry-inspired method for systematic and exhaustive
      evaluation of the symmetry changes possible in molecular systems using molecular
      distortion modes, and how different models can be automatically tested against
      diffraction data. The method produces a quantitative structural landscape from
      which the most appropriate structural description of a child phase can be chosen.
      It can be applied to any molecular or molecular-fragment containing material
      where a (semi) rigid molecule description is appropriate. We exemplify the method
      on 5,6-dichloro-2-methylbenzimidazole (DC-MBI), an important molecular
      ferroelectric. We show that DC-MBI undergoes an unusual symmetry-lowering
      transition on warming from orthorhombic Pca21 ( T ? 400 K) to monoclinic Pc.
      Contrary to expectations, the high temperature phase of DC-MBI remains polar.

PMID- 30230831
TI  - Unraveling the Origin of Solvent Induced Enantioselectivity in the Henry Reaction
      with Cinchona Thiourea as Catalyst.
AB  - In this work, we report an energy decomposition and electronic structure analysis
      using DFT calculations for the C-C coupling step in the Henry reaction with
      cinchona thiourea as catalyst and DMF solvent to unravel the origin of
      enantioselectivity. We found that the conformation of flexible thiourea moiety is
      affected by the solvent, and in the preferred conformation of thiourea in strong
      Lewis basic DMF solvent, the N-H sites are in the opposite direction, i.e., in
      trans conformation. Hence, the thiourea moiety acts via single hydrogen bonding
      with substrates. The conformation of the substrates with respect to the forming C
      C bond plays critical role to increase orbital interaction between two substrates
      and enhances hydrogen bond strength between substrates and catalyst, which in
      turn stabilizes the positive charge developing on the catalyst at the transition
      state for one of the enantiomers ( S). Thus, the enantioselectivity has
      electronic structure origin. The stronger H-bond formation in the S enantiomer
      has been confirmed by the calculated IR spectra and is in agreement with thus far
      experimental and computational results.

PMID- 30230832
TI  - Mode-Specific Quasiclassical Dynamics of the F- + CH3I SN2 and Proton-Transfer
      Reactions.
AB  - Mode-specific quasiclassical trajectory computations are performed for the F- +
      CH3I( v k = 0, 1) SN2 and proton-transfer reactions at nine different collision
      energies in the range of 1.0-35.3 kcal/mol using a full-dimensional high-level ab
      initio analytical potential energy surface with ground-state and excited CI
      stretching ( v3), CH3 rocking ( v6), CH3 umbrella ( v2), CH3 deformation ( v5),
      CH symmetric stretching ( v1), and CH asymmetric stretching ( v4) initial
      vibrational modes. Millions of trajectories provide statistically definitive mode
      specific cross sections, opacity functions, scattering angle distributions, and
      product internal energy distributions. The excitation functions reveal slight
      vibrational SN2 inversion inhibition/enhancement at low/high collision energies (
      Ecoll), whereas large decaying-with- Ecoll vibrational enhancement effects for
      the SN2 retention (double inversion) and proton-transfer channels. The most
      efficient vibrational enhancement is found by exciting the CI stretching (high
      Ecoll) for SN2 inversion and the CH stretching modes (low Ecoll) for double
      inversion and proton transfer. Mode-specific effects do not show up in the
      scattering angle distributions and do blue-shift the hot/cold SN2/proton-transfer
      product internal energies.

PMID- 30230833
TI  - Theoretical Study of the Copper-Catalyzed Hydroarylation of
      (Trifluoromethyl)alkyne with Phenylboronic Acid.
AB  - The copper-catalyzed hydroarylation of 1,1,1-trifluoro-2-butyne with
      phenylboronic acid was investigated by performing density functional theory
      calculations, and a plausible mechanism was proposed. The initial transmetalation
      step was first examined to compare the feasibility of the catalytically active
      copper species. Subsequently, the carbocupration of 1,1,1-trifluoro-2-butyne by
      the phenylcopper species was examined in terms of regioselectivity. The impacts
      of the alkyne terminal group and the para-substituents of phenylboronic acids on
      the carbocupration were also examined. Moreover, to shed light on the role of the
      electron-withdrawing groups on the alkyne substrates, the activation barrier for
      the carbocupration of 1,1,1-trifluoro-2-butyne was compared to those for several
      alkyne substrates bearing ester, ketone, cyano, and pentafluorophenyl groups, as
      well as 2-butyne, which has no electron-withdrawing group. The final
      protodecupration step involving methanol, acetic acid, or phenylboronic acid was
      examined to determine possible proton donors.

PMID- 30230834
TI  - Molecular Dynamics Simulations of Ether- and Ester-Linked Phospholipid Bilayers:
      A Comparative Study of Water Models.
AB  - Membrane dipole potential influences a variety of important biological processes
      involving cell membranes. Because it is quite challenging to directly measure the
      membrane dipole potential in experiments, molecular dynamics (MD) simulation has
      emerged as a powerful tool for a reasonable prediction of the dipole potential.
      Although MD predictions agree well with experiments about the sign of the dipole
      potential, the magnitude of the dipole potential varies significantly with the
      force field parameters. It has been shown that the positive dipole potential of
      phosphatidylcholine (PC) bilayer membranes would be overestimated by a
      nonpolarizable model owing to the treatment of many-body polarization effects in
      a mean-field fashion. In this work, we carried out atomistic MD simulations of
      the diphytanyl PC (ether-DPhPC) and diphytanoyl PC (ester-DPhPC) bilayers and
      made a comparative study of three different nonpolarizable water models (TIP3P,
      TIP4P, and TIP5P). Interestingly, we discover that the calculated dipole
      potential by the TIP5P model shows good agreement with the result obtained using
      the cryoelectron microscopy experiment, suggesting that a better description of
      electrostatic interactions in a nonpolarizable water model can effectively
      ameliorate the overestimation in the calculation of the dipole potential. In
      addition, our MD results show that the substitution of the ether linkage for the
      ester linkage of phospholipid bilayers would bring about a change in the
      orientation of the linkage group with respect to the bilayer normal, leading to
      the difference in the membrane dipole potential. Surprisingly, although water
      molecules provide a major contribution to the positive dipole potential, they
      have a limited impact on the difference of the dipole potential between the ether
      DPhPC and ester-DPhPC bilayer membranes.

PMID- 30230835
TI  - Three-Color Single-Molecule FRET and Fluorescence Lifetime Analysis of Fast
      Protein Folding.
AB  - We describe the theory, experiment, and analysis of three-color Forster resonance
      energy transfer (FRET) spectroscopy for probing conformational dynamics of a fast
      folding protein, alpha3D. In three-color FRET, site-specific labeling of
      fluorophores is required to avoid ambiguity resulting from various species with
      different combinations of labeling positions. To this end, we first attached two
      dyes to a cysteine residue and an unnatural amino acid and then appended a
      cysteine residue to the C-terminus of the protein by the sortase-mediated
      ligation for attaching the third dye. To determine all three FRET efficiencies,
      we used alternating excitation of the donor and acceptor 1 with two picosecond
      pulsed lasers. Since the folded and unfolded states are not distinguishable in
      binned fluorescence trajectories due to fast-folding on a millisecond time scale,
      we used a maximum likelihood method that analyzes photon trajectories without
      binning the data. The extracted kinetic parameters agree very well with the
      previously measured parameters for the same protein with two-color FRET,
      suggesting that the addition of the third fluorophore does not affect the folding
      dynamics of the protein. From the extracted fractions of acceptor photon counts,
      the FRET efficiencies for all three dye pairs were calculated after various
      corrections. They were compared with the FRET efficiencies obtained from the
      global analysis of two-color segments collected in the same experiment. The FRET
      efficiencies of the folded state from the three-color segments agree with those
      from the two-color segments, whereas the three-color and two-color FRET
      efficiencies of the unfolded state are different. This happens because
      fluctuations of all three interdye distances contribute to the FRET efficiency
      measured in three-color FRET. We show that this difference can be accounted for
      by using the Gaussian chain model for the unfolded state with the parameters
      obtained from the analysis of two-color segments. This result shows that three
      color FRET provides additional information on the flexibility of molecules that
      cannot be obtained from a combination of two-color FRET experiments with three
      dye pairs. Using the delay times of photons from the laser pulse, fluorescence
      lifetimes were determined using the maximum likelihood analysis. The correlation
      between FRET efficiencies and lifetimes of the donor, acceptor 1, and acceptor 2
      was visualized in two-dimensional FRET efficiency-lifetime histograms. These
      histograms can be used to demonstrate the presence of conformational dynamics in
      a protein.

PMID- 30230836
TI  - Synthesis, Optoelectronic Properties, Self-Association, and Base Pairing of
      Nucleobase-Functionalized Oligothiophenes.
AB  - Device-relevant pi-conjugated oligothiophenes with the canonical nucleobases
      directly embedded into the pi-framework have been designed, synthesized, and
      characterized. These oligomers offer the ability to tune optoelectronic
      properties via the intimate merging of the nucleobase molecular electronic
      structure with base-pairing fidelity. Analysis of their optical and electronic
      properties in a hydrogen-bond-disrupting solvent (DMF) indicates that the
      nucleobase identity influences the intrinsic electronic properties of the
      semiconductors. These differences are supported by DFT calculations which
      demonstrate that the HOMO/LUMO orbitals are distributed differently for each
      compound. The solubility and competition between self-association and base
      pairing in a hydrogen-bond-supporting solvent (chloroform) was studied to better
      understand the oligomer behavior under conditions relevant for downstream
      solution processing into thin-film devices. These solution studies reveal that in
      each case base-pairing is preferred to self-aggregation; the relatively weak
      heteroassociation of 1A-1U (35 +/- 5 M-1) should be amenable to facile solution
      processing and successive hydrogen bond formation in the solid state, while the
      strong heteroassociation between 1G and 1C (>104 M-1) should enable assemblies to
      be preformed in solution. These results are expected to enable the synthesis of
      more complex pi-conjugated architectures and facilitate their extension to
      optoelectronic devices.

PMID- 30230837
TI  - Unexpected Reaction Pathways Leading to Thiodiglycol During the Degradation of
      Long-Chain Sulfur Mustards.
AB  - Degradation of long-chain sulfur mustards with various commercial decontaminants
      unexpectedly forms thiodiglycol (TDG) through unreported reaction pathways.
      Chemical warfare agents (CWAs) degradation products have to be unambiguously
      related to their reference compounds in order to fulfill international
      verification protocols. Thus, the formation of TDG using water-based
      decontaminants introduces an uncertainty in the origin of this chemical that has
      been systematically used to unambiguously demonstrate the presence of yperite in
      environmental and biomedical samples. Therefore, these novel and unprecedented
      degradation pathways will result either in modifications of the international
      verification protocols for forensic purposes or in the exclusion of TDG as an
      exclusive marker of yperite.

PMID- 30230838
TI  - Peptide and Protein Structure Prediction with a Simplified Continuum Solvent
      Model.
AB  - A continuum solvent model based on screened Coulomb potentials has been
      simplified and parametrized to sample native-like structures in replica-exchange
      simulations of each of six different peptides and miniproteins. Low-energy,
      native, and non-native structures were used to iteratively refine 11 parameter
      values. The centroid of the largest cluster of structures sampled in simulations
      initiated from an extended conformation represents the predicted structure. The
      main-chain rms deviation of this prediction from the experimental structure was
      0.47 A for the 12-residue Trp-zip2, 0.86 A for the 14-residue MBH12, 2.53 A for
      the 17-residue U(1-17)T9D, 2.03 A for the 20-residue BS1, 1.08 A for the 20
      residue Trp-cage, and 3.64 A for the 35-residue villin headpiece subdomain HP35.
      The centroid of the sixth largest cluster sampled for HP35 deviated by 0.91 A.
      The CHARMM22/CMAP force field was used, with an additional psi torsion term for
      residues other than glycine and proline. Six parameters govern the dielectric
      response of the continuum solvent, and four values of surface tension approximate
      nonpolar effects. An atom's self-energy and interaction energies are screened
      independently, each depending on whether the atom is part of a charged group, a
      neutral hydrogen-bonding main-chain group, or any other neutral group. The
      parameters inferred result in strong main-chain hydrogen bonds, consistent with
      the view that protein folding is dominated by the formation of these bonds. (1,2)
      Conformations of MBH12 and BS1 were excluded from the energy-function refinement,
      suggesting the parameters, referred to as SCP18, are transferable. An efficient
      estimate of solvent-accessible surface area is also described.

PMID- 30230839
TI  - Atomistic Modeling of Intrinsically Disordered Proteins Under Polyethylene Glycol
      Crowding: Quantitative Comparison with Experimental Data and Implication of
      Protein-Crowder Attraction.
AB  - The malleability of intrinsically disordered proteins (IDPs) has generated great
      interest in understanding how their conformations respond to crowded cellular
      environments. Experiments can report gross properties such as fluorescence
      resonance energy transfer (FRET) efficiency but cannot resolve the conformational
      ensembles of IDPs and their interactions with macromolecular crowders.
      Computation can in principle provide the latter information but in practice has
      been hampered by the enormous expense for realistic modeling of IDPs and crowders
      and for sufficient conformational sampling. Here, taking advantage of a powerful
      method called FMAP (fast Fourier transform-based modeling of atomistic protein
      crowder interactions), we computed how the conformational ensembles of three IDPs
      are modified in concentrated polyethylene glycol (PEG) 6000 solutions. We
      represented the IDPs at the all-atom level and the PEG molecules at a coarse
      grained level and calculated the experimental observable, i.e., FRET efficiency.
      Whereas accounting for only steric repulsion of PEG led to overestimation of
      crowding effects, quantitative agreement with experimental data was obtained upon
      including mild IDP-PEG attraction. The present work demonstrates that realistic
      modeling of IDPs under crowded conditions for direct comparison with experiments
      is now achievable.

PMID- 30230840
TI  - Multibond Forming Tandem Reactions of Anilines via Stable Aryl Diazonium Salts:
      One-Pot Synthesis of 3,4-Dihydroquinolin-2-ones.
AB  - A fast and effective one-pot tandem process that generates Heck coupled products
      from readily available anilines via stable aryl diazonium tosylate salts was
      developed. The mild and simple procedure involves rapid formation of aryl
      diazonium salts using a polymer-supported nitrite reagent and p-tosic acid,
      followed by a base-free Heck-Matsuda coupling with acrylates and styrenes. Using
      2-nitroanilines as substrates, the one-pot tandem process was extended for the
      direct synthesis of 3,4-dihydroquinolin-2-ones. In this case, following
      diazotization and Heck-Matsuda coupling to give methyl cinnamates, addition of
      hydrogen and reutilization of the palladium catalyst for reduction of the nitro
      group and hydrogenation of the alkene resulted in efficient formation of 3,4
      dihydroquinolin-2-ones. The synthetic utility of this one-pot, four-stage process
      was demonstrated with the five-pot synthesis of a quinolinone-based sodium ion
      channel modulator.

PMID- 30230841
TI  - Molecular Photon Upconversion Solar Cells Using Multilayer Assemblies: Progress
      and Prospects.
AB  - Molecular photon upconversion via triplet-triplet annihilation (TTA-UC) is an
      intriguing strategy to increase solar cell efficiencies and surpass the Shockley
      Quiesser (SQ) limit. In this Perspective, we recount our group's efforts to
      harness TTA-UC by directly incorporating metal ion linked multilayers of acceptor
      and sensitizer molecules into an organic-inorganic hybrid solar cell
      architecture. These self-assembled multilayers facilitate both upconverted
      emission and photocurrent generation from the upconverted state with a record
      contribution of 0.158 mA cm-2 under 1 sun solar flux. We recount the progression
      toward this record and the mechanistic insights learned along the way, summarize
      the rate- and efficiency-limiting events, and outline improvements that must be
      made to produce a viable TTA-UC solar cell that can surpass the SQ limit. We also
      discuss the potential impact that efficient TTA-UC and photocurrent generation
      could have on existing record solar cells.

PMID- 30230842
TI  - Elimination of S Vacancy as the Cause for the n-Type Behavior of MoS2 from the
      First-Principles Perspective.
AB  - Molybdenum disulfide (2H-MoS2) based low-dimensional nanostructure materials have
      great potential for applications in electronic and optoelectronic devices.
      However, some of the properties such as the origin of the native n-type
      electrical conductivity (EC) observed in these materials still remain elusive.
      Here, the defect properties in the 2H-MoS2 bulk system are systematically
      investigated by first-principles calculation to address these issues. We find
      that the S vacancy VS with low formation energy cannot be the origin of n-type EC
      owing to its deep defect levels within the valence band region. All other donor
      defects such as antisite MoS or Mo interstitial MoI also have deep levels that
      can trap electrons leading to depressed EC. SMo and SI could be the origin of the
      p-type EC in 2H-MoS2, but the concentrations are expected to be rather low due to
      their high formation energies and can only be enhanced under S-rich/Mo-poor
      conditions. These results provide the underlying insights on the defect
      properties 2H-MoS2 and explain well the experimental observations.

PMID- 30230843
TI  - Adiabatic Ligand Binding in Heme Proteins: Ultrafast Kinetics of Methionine
      Rebinding in Ferrous Cytochrome c.
AB  - The dynamics of methionine geminate recombination following photodissociation in
      ferrous cytochrome c is investigated over a broad temperature range. The kinetic
      response, above the solvent glass transition ( Tg), is nearly monoexponential and
      displays a weak temperature dependence. Below Tg, the rebinding kinetics are
      nonexponential and can be explained using a quenched distribution of enthalpic
      rebinding barriers, arising from a relatively narrow distribution of heme out-of
      plane displacements. The Arrhenius prefactor of this (Delta S = 2) reaction is
      ~1011 s-1, which is similar to what has been found for the (Delta S = 1) NO
      binding reaction in heme proteins. This observation, along with other examples of
      ultrafast CO binding, provides strong evidence that ligand binding to heme is an
      adiabatic reaction with a spin-independent prefactor. In order to simultaneously
      account for the adiabatic nature of the reaction as well as the temperature
      dependence of both ultrafast CO and methionine geminate rebinding, it is proposed
      that a spin triplet state intersects and strongly couples to the reactant ( S =
      2) and product ( S = 0) state surfaces in the transition state region along the
      reaction coordinate. It is also suggested that the nature of the intersecting
      triplet state and the reaction path may depend upon the proximity of the
      photolyzed ligand relative to the iron atom. At temperatures below ~60 K, the
      kinetic data suggest that there is either an unexpected retardation of the heme
      photoproduct relaxation or that heavy atom quantum mechanical tunneling becomes
      significant.

PMID- 30230844
TI  - Cold-Adaptation Signatures in the Ligand Rebinding Kinetics to the Truncated
      Hemoglobin of the Antarctic Bacterium Pseudoalteromonas haloplanktis TAC125.
AB  - Cold-adapted organisms have evolved proteins endowed with higher flexibility and
      lower stability in comparison to their thermophilic homologues, resulting in
      enhanced reaction rates at low temperatures. In this context, protein-bound water
      molecules were suggested to play a major role, and their weaker interactions at
      protein active sites have been associated with cold adaptation. In this work, we
      tested this hypothesis on truncated hemoglobins (a family of microbial heme
      proteins of yet-unclear function) applying molecular dynamics simulations and
      ligand-rebinding kinetics on a protein from the Antarctic bacterium
      Pseudoalteromonas haloplanktis TAC125 in comparison with its thermophilic
      Thermobifida fusca homologue. The CO rebinding kinetics of the former highlight
      several geminate phases, with an unusually long-lived geminate intermediate. An
      articulated tunnel with at least two distinct docking sites was identified by
      analysis of molecular dynamics simulations and was suggested to be at the origin
      of the unusual geminate rebinding phase. Water molecules are present in the
      distal pocket, but their stabilization by TrpG8, TyrB10, and HisCD1 is much
      weaker than in thermophilic Thermobifida fusca truncated hemoglobin, resulting in
      a faster geminate rebinding. Our results support the hypothesis that weaker water
      molecule interactions at the reaction site are associated with cold adaptation.

PMID- 30230845
TI  - Interactions of Fly Ash Particles with Mucin and Serum Albumin.
AB  - Fly ash particles can contribute to haze and adverse health outcomes. In this
      study, two mucins, one from bovine submaxillary glands (bovine submaxillary
      mucin, BSM) and one from porcine stomach (porcine gastric mucin), as well as
      bovine serum albumin (BSA), which served as the physical barriers against foreign
      substances entering the tissues and the blood protein, respectively, were chosen
      as models for the investigations of the interactions between the proteins and the
      fly ash particles. Their adsorption behaviors were studied using spectroscopy and
      a quartz crystal microbalance with a dissipation monitor (QCM-D). The results
      indicated that the fly ash particles can induce the loosening of mucins and BSA,
      probably via the formation of complexes. Further, the secondary structure of
      proteins changed in the presence of fly ash particles. The alpha-helix content
      decreased with an increasing fly ash particle concentration. The addition of fly
      ash particles into protein solutions led to fluorescence quenching, which
      suggested that there were interactions between these particles and the mucins and
      BSA. The association constants ( Ka) for BSM and BSA were 5.35 and 4.18 L/g,
      respectively. Furthermore, the results of QCM-D analyses showed that the amount
      decreased on the mucin surface but increased slightly on the BSA surface, which
      indicated that the fly ash particles disrupted the mucin layer upon adsorption.
      These findings provide clear evidence of the interactions between the fly ash
      particles and the mucins and BSA, which can lead to structural changes. This
      study contributes to a better understanding of the interactions and adsorptions
      of atmospheric particulate pollutants with the proteins in the human body.

PMID- 30230846
TI  - Size-Defined Cracked Vesicle Formation via Self-Assembly of Gold Nanoparticles
      Covered with Carboxylic Acid-Terminated Surface Ligands.
AB  - The self-assembly of gold nanoparticles (GNPs) into a defined structure,
      particularly hollow capsule structures, provides great potential for applications
      in materials science and medicine. However, the complexity of the parameters for
      the preparation of those structures through self-assembly has limited access to
      critical mechanistic questions. With this in mind, we have studied GNP vesicle
      (GNV) formation through self-assembly by the surface modification of GNPs with
      low-molecular-weight ligands. Here, we successfully prepared GNVs composed of
      GNPs with a diameter of 30 nm by surface modification with carboxylic acid
      terminated fluorinated oligo(ethylene glycol) ligands (CFLs). As the carboxylic
      acid has two states (protonated and deprotonated), the balance of the attraction
      and repulsion between GNPs covered with CFLs is tunable. Sodium carboxylate
      terminated fluorinated oligo(ethylene glycol) ligands (SCFLs) provided smaller
      GNVs than did CFLs at 0.8 * 1011 NPs/mL. Time-course study revealed that CFL
      covered GNPs quickly form small aggregates and gradually grow to larger GNVs (ca.
      200 nm), but no gradual growth was observed for SCFL-covered GNPs. This result
      indicated that the electrostatic repulsion inhibits fusion of the small GNVs. The
      size of the GNVs formed with the aid of CFLs was independent of the initial GNP
      concentration, but the extinction spectra were concentration-dependent. Electron
      microscopy imaging and simulations supported the defect formation in the
      assemblies. These results provided new insights into the vesicle formation
      mechanism.

PMID- 30230847
TI  - Ultrafast Structure and Dynamics in the Thermally Activated Delayed Fluorescence
      of a Carbene-Metal-Amide.
AB  - Thermally activated delayed fluorescence has enormous potential for the
      development of efficient light emitting diodes. A recently discovered class of
      molecules (the carbene-metal-amides, CMAs) are exceptionally promising as they
      combine the small singlet-triplet energy gap required for thermal activation with
      a large transition moment for emission. Calculations suggest excited state
      structural dynamics modulate the critical coupling between singlet and triplet,
      but they disagree on the nature of those dynamics. Here we report ultrafast time
      resolved transient absorption and Raman studies of CMA photodynamics. The
      measurements reveal complex structural evolution following intersystem crossing
      on the tens to hundreds of picoseconds time scale, and a change in the low
      frequency vibrational spectrum between singlet and triplet states. The latter is
      assigned to changes in Raman active modes localized on the metal center.

PMID- 30230848
TI  - Unidirectional Droplet Transport on the Biofabricated Butterfly Wing.
AB  - Water droplet unidirectional transport on the asymmetric superhydrophobic surface
      has attracted much interest in theory analysis and applications, such as self
      cleaning, antifogging, anti-icing, heat transfer, and so on. Different from the
      symmetrical performance on the uniform topographies, the droplets acting on the
      asymmetric surface exhibit an anisotropic state and easily roll off the surface
      along the special direction. This phenomenon is indicated by natural butterfly
      wings. The flexible asymmetrically arranged microstep induces the droplet to
      release along the outside radial (RO) direction and to pin against the RO
      direction. Here, inspired by butterfly wings, a kind of surface for
      superhydrophobic and unidirectional droplet transport is achieved by integrating
      the methods of soft lithography and enhanced crystal growth. The water droplet
      shows the anisotropic state on the biofabricated surface, and it rolls off easily
      along the step direction. The droplet is unidirectionally driven off the surface
      by the asymmetric surface tension force generated by the microstep topography.
      This experiment is significant for designing self-cleaning surfaces.

PMID- 30230849
TI  - All-Atom Molecular Dynamics Simulations of Whole Viruses.
AB  - Classical molecular dynamics modeling of whole viruses or their capsids in
      explicit water is discussed, and known examples from the literature are analyzed.
      Only works on all-atom modeling in explicit water are included. Physical
      chemistry of the whole system is the focus, which includes the structure and
      dynamics of the biomolecules as well as water and ion behavior in and around the
      virus particle. It was demonstrated that in most investigations molecular
      phenomena that currently can not be studied experimentally are successfully
      reproduced and explained by the simulations. These include, for example,
      transport and distribution of ions inside viruses that ultimately connected to
      their stability, the hydrodynamic pressure in the capsid related to viruses'
      elastic properties, the role of metal ions in virus swelling, and others. Current
      and future tendencies in the development of all-atom virus simulations are
      outlined.

PMID- 30230850
TI  - Tilted Electron Pulses.
AB  - We report the all-optical generation and characterization of tilted electron
      pulses by means of single-cycle terahertz radiation at an electron-transmitting
      mirror at slanted orientation. Femtosecond electron pulses with a chosen tilt
      angle are produced at an almost arbitrary target location. The experiments along
      with theory further reveal that the pulse front tilt in electron optics is
      directly connected to angular dispersion. Quantum mechanical considerations
      suggest that this relation is general for particle beams at any degree of
      coherence. These results indicate that ultrashort electron pulses can be shaped
      in space and time as versatilely as femtosecond laser pulses, but at 10^{5} times
      finer wavelength and subnanometer imaging resolution.

PMID- 30230852
TI  - Anomalous Scaling of Dynamical Large Deviations.
AB  - The typical values and fluctuations of time-integrated observables of
      nonequilibrium processes driven in steady states are known to be characterized by
      large deviation functions, generalizing the entropy and free energy to
      nonequilibrium systems. The definition of these functions involves a scaling
      limit, similar to the thermodynamic limit, in which the integration time tau
      appears linearly, unless the process considered has long-range correlations, in
      which case tau is generally replaced by tau^{xi} with xi?1. Here, we show that
      such an anomalous power-law scaling in time of large deviations can also arise
      without long-range correlations in Markovian processes as simple as the Langevin
      equation. We describe the mechanism underlying this scaling using path integrals
      and discuss its physical consequences for more general processes.

PMID- 30230853
TI  - Thermal Conductivity and Electrical Resistivity of Solid Iron at Earth's Core
      Conditions from First Principles.
AB  - We compute the thermal conductivity and electrical resistivity of solid hcp Fe to
      pressures and temperatures of Earth's core. We find significant contributions
      from electron-electron scattering, usually neglected at high temperatures in
      transition metals. Our calculations show a quasilinear relation between the
      electrical resistivity and temperature for hcp Fe at extreme high pressures. We
      obtain thermal and electrical conductivities that are consistent with experiments
      considering reasonable error. The predicted thermal conductivity is reduced from
      previous estimates that neglect electron-electron scattering. Our estimated
      thermal conductivity for the outer core is 77+/-10  W m^{-1} K^{-1} and is
      consistent with a geodynamo driven by thermal convection.

PMID- 30230855
TI  - Erratum: Prediction for a Four-Neutron Resonance [Phys. Rev. Lett. 117, 182502
      (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.117.182502.

PMID- 30230854
TI  - Fluctuations of Energy-Relaxation Times in Superconducting Qubits.
AB  - Superconducting qubits are an attractive platform for quantum computing since
      they have demonstrated high-fidelity quantum gates and extensibility to modest
      system sizes. Nonetheless, an outstanding challenge is stabilizing their energy
      relaxation times, which can fluctuate unpredictably in frequency and time. Here,
      we use qubits as spectral and temporal probes of individual two-level-system
      defects to provide direct evidence that they are responsible for the largest
      fluctuations. This research lays the foundation for stabilizing qubit performance
      through calibration, design, and fabrication.

PMID- 30230856
TI  - Structural Nonequilibrium Forces in Driven Colloidal Systems.
AB  - We identify a structural one-body force field that sustains spatial
      inhomogeneities in nonequilibrium overdamped Brownian many-body systems. The
      structural force is perpendicular to the local flow direction, it is free of
      viscous dissipation, it is microscopically resolved in both space and time, and
      it can stabilize density gradients. From the time evolution in the exact
      (Smoluchowski) low-density limit, Brownian dynamics simulations, and a novel
      power functional approximation, we obtain a quantitative understanding of viscous
      and structural forces, including memory and shear migration.

PMID- 30230857
TI  - Standard Model Fermions and Infinite-Dimensional R Symmetries.
AB  - Following up on our earlier work [K. A. Meissner and H. Nicolai, Phys. Rev. D 91,
      065029 (2015)] where we showed how to amend a scheme originally proposed by M.
      Gell-Mann to identify the 48 spin-1/2 fermions of N=8 supergravity that remain
      after complete breaking of N=8 supersymmetry with the 3*16 quarks and leptons of
      the standard model, we further generalize the construction to account for the
      full SU(3)_{c}*SU(2)_{w}*U(1)_{Y} assignments, with an additional family symmetry
      SU(3)_{f}. Our proposal relies in an essential way on embedding the SU(8) R
      symmetry of N=8 supergravity into the (infinite-dimensional) "maximal compact"
      subgroup K(E_{10}) of the conjectured maximal duality symmetry E_{10}. As a by
      product, it predicts fractionally charged and possibly strongly interacting
      massive gravitinos. It also indicates how E_{10} and K(E_{10}) can supersede
      supersymmetry as a guiding principle for unification.

PMID- 30230858
TI  - Rotation-Symmetry-Enforced Coupling of Spin and Angular Momentum for p-Orbital
      Bosons.
AB  - Intrinsic spin angular-momentum coupling of an electron has a relativistic
      quantum origin with the coupling arising from charged orbits, which does not
      carry over to charge-neutral atoms. Here, we propose a mechanism of spontaneous
      generation of spin angular-momentum coupling with spinor atomic bosons loaded
      into p-orbital bands of a two-dimensional optical lattice. This spin angular
      momentum coupling originates from many-body correlations and spontaneous symmetry
      breaking in a superfluid, with the key ingredients attributed to spin-channel
      quantum fluctuations and an approximate rotation symmetry. The resultant spin
      angular-momentum intertwined superfluid has Dirac excitations. In the presence of
      a chemical potential difference for adjacent sites, it provides a bosonic
      analogue of a symmetry-protected-topological insulator. Through a dynamical mean
      field calculation, this novel superfluid is found to be a generic low-temperature
      phase, and it gives way to Mott localization only at strong interactions and even
      integer fillings. We show the temperature to reach this order is accessible with
      present experiments.

PMID- 30230859
TI  - Topological Waveguiding near an Exceptional Point: Defect-Immune, Slow-Light, and
      Loss-Immune Propagation.
AB  - Electromagnetic waves propagating in conventional wave-guiding structures are
      reflected by discontinuities and decay in lossy regions. In this Letter, we
      drastically modify this typical guided-wave behavior by combining concepts from
      non-Hermitian physics and topological photonics. To this aim, we theoretically
      study, for the first time, the possibility of realizing an exceptional point
      between coupled topological modes in a non-Hermitian nonreciprocal waveguide. Our
      proposed system is composed of oppositely biased gyrotropic materials (e.g.,
      biased plasmas or graphene layers) with a balanced distribution of loss and gain.
      To study this complex wave-guiding problem, we put forward an exact analysis
      based on classical Green's function theory, and we elucidate the behavior of
      coupled topological modes and the nature of their non-Hermitian degeneracies. We
      find that, by operating near an exceptional point, we can realize anomalous
      topological wave propagation with, at the same time, low group velocity, inherent
      immunity to backscattering at discontinuities, and immunity to losses. These
      theoretical findings may open exciting research directions and stimulate further
      investigations of non-Hermitian topological waveguides to realize robust wave
      propagation in practical scenarios.

PMID- 30230860
TI  - Majorana Corner Modes in a High-Temperature Platform.
AB  - We introduce two-dimensional topological insulators in proximity to high
      temperature cuprate or iron-based superconductors as high-temperature platforms
      of Majorana Kramers pairs of zero modes. The proximity-induced pairing at the
      helical edge state of the topological insulator serves as a Dirac mass, whose
      sign changes at the sample corner because of the pairing symmetry of high-T_{c}
      superconductors. This sign changing naturally creates at each corner a pair of
      Majorana zero modes protected by time-reversal symmetry. Conceptually, this is a
      topologically trivial superconductor-based approach for Majorana zero modes. We
      provide quantitative criteria and suggest candidate materials for this proposal.

PMID- 30230861
TI  - Monodromy Inflation in the Strong Coupling Regime of the Effective Field Theory.
AB  - We present a simple effective field theory formulation of a general family of
      single-field flux monodromy models for which strong coupling effects at large
      field values can flatten the potential and activate higher-derivative operators.
      Both of these effects can suppress the tensor amplitude. These models are
      radiatively and nonperturbatively stable and can sustain ?60 e folds of
      inflation. The dynamics combines features of both large-field chaotic inflation
      and k inflation. Reducing the tensor-scalar ratio below the observational bound
      r?0.1 while keeping the scalar spectral index n_{s} within experimental bounds
      either yields equilateral non-Gaussianity f_{NL}^{eq}?O(1), close to the current
      observational bounds, or gives very small r.

PMID- 30230862
TI  - Flatbands and Emergent Ferromagnetic Ordering in Fe_{3}Sn_{2} Kagome Lattices.
AB  - A flatband representing a highly degenerate and dispersionless manifold state of
      electrons may offer unique opportunities for the emergence of exotic quantum
      phases. To date, definitive experimental demonstrations of flatbands remain to be
      accomplished in realistic materials. Here, we present the first experimental
      observation of a striking flatband near the Fermi level in the layered
      Fe_{3}Sn_{2} crystal consisting of two Fe kagome lattices separated by a Sn
      spacing layer. The band flatness is attributed to the local destructive
      interferences of Bloch wave functions within the kagome lattices, as confirmed
      through theoretical calculations and modelings. We also establish high
      temperature ferromagnetic ordering in the system and interpret the observed
      collective phenomenon as a consequence of the synergetic effect of electron
      correlation and the peculiar lattice geometry. Specifically, local spin moments
      formed by intramolecular exchange interaction are ferromagnetically coupled
      through a unique network of the hexagonal units in the kagome lattice. Our
      findings have important implications to exploit emergent flat-band physics in
      special lattice geometries.

PMID- 30230863
TI  - Dynamical Critical Exponents in Driven-Dissipative Quantum Systems.
AB  - We study the phase ordering of parametrically and incoherently driven microcavity
      polaritons after an infinitely rapid quench across the critical region. We
      confirm that the system, despite its driven-dissipative nature, satisfies the
      dynamical scaling hypothesis for both driving schemes by exhibiting self-similar
      patterns for the two-point correlator at late times of the phase ordering. We
      show that polaritons are characterized by the dynamical critical exponent z~2
      with topological defects playing a fundamental role in the dynamics, giving
      logarithmic corrections both to the power-law decay of the number of vortices and
      to the associated growth of the characteristic length scale.

PMID- 30230864
TI  - Monopole-Induced Emergent Electric Fields in Ferromagnetic Nanowires.
AB  - We predict that complete magnetization reversal in simple metallic ferromagnetic
      nanoparticles is directly linked to the pair creation of topological point
      defects in the form of hedgehog-antihedgehog pairs. These dynamical point defects
      move at exceptionally high speeds in excess of 1500  m/s, faster than any other
      known magnetic object. Their rapid motion generates unprecedented solenoidal
      emergent fields on the order of megavolts per meter, in analogy to the magnetic
      field of a moving electric charge, providing a striking example that a moving
      hedgehog constitutes an emergent magnetic monopole.

PMID- 30230865
TI  - Rydberg Excitons in the Presence of an Ultralow-Density Electron-Hole Plasma.
AB  - We study the Rydberg exciton absorption of Cu_{2}O in the presence of free
      carriers injected by above-band-gap illumination. Already at plasma densities
      rho_{EH} below one hundredth electron-hole pair per MUm^{3}, exciton lines are
      bleached, starting from the highest observed principal quantum number, while
      their energies remain constant. Simultaneously, the band gap decreases by
      correlation effects with the plasma. An exciton line loses oscillator strength
      when the band gap approaches its energy, vanishing completely at the crossing
      point. Adapting a plasma-physics description, we describe the observations by an
      effective Bohr radius that increases with rising plasma density, reflecting the
      Coulomb interaction screening by the plasma.

PMID- 30230866
TI  - Equilibrium Shapes and Their Stability for Liquid Films in Fast Flows.
AB  - We study how a suspended liquid film is deformed by an external flow en route to
      forming a bubble through experiments and a model. We identify a family of
      nonminimal but stable equilibrium shapes for flow speeds up to a critical value
      beyond which the film inflates unstably, and the model accounts for the observed
      nonlinear deformations and forces. A saddle-node or fold bifurcation in the
      solution diagram suggests that bubble formation at high speeds results from the
      loss of equilibrium and at low speeds from the loss of stability for overly
      inflated shapes.

PMID- 30230868
TI  - Quantum Relaxation and Metastability of Lattice Bosons with Cavity-Induced Long
      Range Interactions.
AB  - The coupling of cold atoms to the radiation field within a high-finesse optical
      resonator, an optical cavity, induces long-range interactions which can compete
      with an underlying optical lattice. The interplay between short- and long-range
      interactions gives rise to new phases of matter including supersolidity (SS) and
      density waves (DW), and interesting quantum dynamics. Here it is shown that for
      hard-core bosons in one dimension the ground state phase diagram and the quantum
      relaxation after sudden quenches can be calculated exactly in the thermodynamic
      limit. Remanent DW order is observed for quenches from a DW ground state into the
      superfluid (SF) phase below a dynamical transition line. After sufficiently
      strong SF to DW quenches beyond a static metastability line DW order emerges on
      top of remanent SF order, giving rise to a dynamically generated SS state. Our
      method to handle infinite- and short-range interactions in the infinite system
      size limit opens a way to solve exactly other Hamiltonians with infinite- and
      short-range interactions as well.

PMID- 30230867
TI  - Erratum: Persistence of the Z=28 Shell Gap Around ^{78}Ni: First Spectroscopy of
      ^{79}Cu [Phys. Rev. Lett. 119, 192501 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.192501.

PMID- 30230870
TI  - Thermally Driven Out-of-Equilibrium Two-Impurity Kondo System.
AB  - The archetypal two-impurity Kondo problem in a serially coupled double quantum
      dot is investigated in the presence of a thermal bias theta. The slave-boson
      formulation is employed to obtain the nonlinear thermal and thermoelectrical
      responses. When the Kondo correlations prevail over the antiferromagnetic
      coupling J between dot spins, we demonstrate that the setup shows negative
      differential thermal conductance regions behaving as a thermal diode. In
      addition, we report a sign reversal of the thermoelectric current I(theta)
      controlled by t/Gamma (t and Gamma denote the interdot tunnel and reservoir-dot
      tunnel couplings, respectively) and theta. All these features are attributed to
      the fact that at large theta both Q(theta) (heat current) and I(theta) are
      suppressed regardless of the value of t/Gamma because the double dot decouples at
      high thermal biases. Finally, for a finite J, we investigate how the Kondo-to
      antiferromagnetic crossover is altered by theta.

PMID- 30230871
TI  - Damping of Josephson Oscillations in Strongly Correlated One-Dimensional Atomic
      Gases.
AB  - We study Josephson oscillations of two strongly correlated one-dimensional
      bosonic clouds separated by a localized barrier. Using a quantum-Langevin
      approach and the exact Tonks-Girardeau solution in the impenetrable-boson limit,
      we determine the dynamical evolution of the particle-number imbalance, displaying
      an effective damping of the Josephson oscillations which depends on barrier
      height, interaction strength, and temperature. We show that the damping
      originates from the quantum and thermal fluctuations intrinsically present in the
      strongly correlated gas. Because of the density-phase duality of the model, the
      same results apply to particle-current oscillations in a one-dimensional ring
      where a weak barrier couples different angular momentum states.

PMID- 30230872
TI  - Tidal Deformabilities and Radii of Neutron Stars from the Observation of
      GW170817.
AB  - We use gravitational-wave observations of the binary neutron star merger GW170817
      to explore the tidal deformabilities and radii of neutron stars. We perform a
      Bayesian parameter estimation with the source location and distance informed by
      electromagnetic observations. We also assume that the two stars have the same
      equation of state; we demonstrate that, for stars with masses comparable to the
      component masses of GW170817, this is effectively implemented by assuming that
      the stars' dimensionless tidal deformabilities are determined by the binary's
      mass ratio q by Lambda_{1}/Lambda_{2}=q^{6}. We investigate different choices of
      prior on the component masses of the neutron stars. We find that the tidal
      deformability and 90% credible interval is Lambda[over ~]=222_{-138}^{+420} for a
      uniform component mass prior, Lambda[over ~]=245_{-151}^{+453} for a component
      mass prior informed by radio observations of Galactic double neutron stars, and
      Lambda[over ~]=233_{-144}^{+448} for a component mass prior informed by radio
      pulsars. We find a robust measurement of the common areal radius of the neutron
      stars across all mass priors of 8.9<=R[over ^]<=13.2  km, with a mean value of
      ?R[over ^]?=10.8  km. Our results are the first measurement of tidal
      deformability with a physical constraint on the star's equation of state and
      place the first lower bounds on the deformability and areal radii of neutron
      stars using gravitational waves.

PMID- 30230873
TI  - Theory of the Topological Spin Hall Effect in Antiferromagnetic Skyrmions: Impact
      on Current-Induced Motion.
AB  - We demonstrate that the nontrivial magnetic texture of antiferromagnetic
      Skyrmions (AFM Sks) promotes a nonvanishing topological spin Hall effect (TSHE)
      on the flowing electrons. This effect results in a substantial enhancement of the
      nonadiabatic torque and, hence, improves the Skyrmion mobility. This nonadiabatic
      torque increases when decreasing the Skyrmion size, and, therefore, scaling down
      results in a much higher torque efficiency. In clean AFM Sks, we find a
      significant boost of the TSHE close to the van Hove singularity. Interestingly,
      this effect is enhanced away from the band gap in the presence of nonmagnetic
      interstitial defects. Furthermore, unlike their ferromagnetic counterpart, the
      TSHE in AFM Sks increases with an increase in the disorder strength, thus opening
      promising avenues for materials engineering of this effect.

PMID- 30230874
TI  - Full Phase Diagram of Active Brownian Disks: From Melting to Motility-Induced
      Phase Separation.
AB  - We establish the complete phase diagram of self-propelled hard disks in two
      spatial dimensions from the analysis of the equation of state and the statistics
      of local order parameters. The equilibrium melting scenario is maintained at
      small activities, with coexistence between active liquid and hexatic order,
      followed by a proper hexatic phase, and a further transition to an active solid.
      As activity increases, the emergence of hexatic and solid order is shifted
      towards higher densities. Above a critical activity and for a certain range of
      packing fractions, the system undergoes motility-induced phase separation and
      demixes into low and high density phases; the latter can be either disordered
      (liquid) or ordered (hexatic or solid) depending on the activity.

PMID- 30230875
TI  - Biermann-Battery-Mediated Magnetic Reconnection in 3D Colliding Plasmas.
AB  - Recent experiments have demonstrated magnetic reconnection between colliding
      plasma plumes, where the reconnecting magnetic fields were self-generated in the
      plasma by the Biermann-battery effect. Using fully kinetic 3D simulations, we
      show the full evolution of the magnetic fields and plasma in these experiments,
      including self-consistent magnetic field generation about the expanding plume.
      The collision of the two plasmas drives the formation of a current sheet, where
      reconnection occurs in a strongly time- and space-dependent manner, demonstrating
      a new 3D reconnection mechanism. Specifically, we observe a fast, vertically
      localized Biermann-mediated reconnection, an inherently 3D process where the
      temperature profile in the current sheet coupled with the out-of-plane ablation
      density profile conspires to break inflowing field lines, reconnecting the field
      downstream. Fast reconnection is sustained by both the Biermann effect and the
      traceless electron pressure tensor, where the development of plasmoids appears to
      modulate the contribution of the latter. We present a simple and general
      formulation to consider the relevance of Biermann-mediated reconnection in
      general astrophysical scenarios.

PMID- 30230869
TI  - Center of Mass Motion of Short-Range Correlated Nucleon Pairs studied via the
      A(e,e^{'}pp) Reaction.
AB  - Short-range correlated (SRC) nucleon pairs are a vital part of the nucleus,
      accounting for almost all nucleons with momentum greater than the Fermi momentum
      (k_{F}). A fundamental characteristic of SRC pairs is having large relative
      momenta as compared to k_{F}, and smaller center of mass (c.m.) which indicates a
      small separation distance between the nucleons in the pair. Determining the c.m.
      momentum distribution of SRC pairs is essential for understanding their formation
      process. We report here on the extraction of the c.m. motion of proton-proton
      (pp) SRC pairs in carbon and, for the first time in heavier and ansymetric
      nuclei: aluminum, iron, and lead, from measurements of the A(e,e^{'}pp) reaction.
      We find that the pair c.m. motion for these nuclei can be described by a three
      dimensional Gaussian with a narrow width ranging from 140 to 170  MeV/c,
      approximately consistent with the sum of two mean-field nucleon momenta.
      Comparison with calculations appears to show that the SRC pairs are formed from
      mean-field nucleons in specific quantum states.

PMID- 30230876
TI  - Quantum-Limited Time-Frequency Estimation through Mode-Selective Photon
      Measurement.
AB  - By projecting onto complex optical mode profiles, it is possible to estimate
      arbitrarily small separations between objects with quantum-limited precision,
      free of uncertainty arising from overlapping intensity profiles. Here we extend
      these techniques to the time-frequency domain using mode-selective sum-frequency
      generation with shaped ultrafast pulses. We experimentally resolve temporal and
      spectral separations between incoherent mixtures of single-photon level signals
      ten times smaller than their optical bandwidths with a tenfold improvement in
      precision over the intensity-only Cramer-Rao bound.

PMID- 30230877
TI  - Elementary Edge and Screw Dislocations Visualized at the Lattice Periodicity
      Level in the Smectic Phase of Colloidal Rods.
AB  - Topological defects such as dislocations play a major role in science, from
      condensed matter and geophysics to cosmology. These line defects present in
      periodically ordered structures mediate phase transitions and determine many
      distinctive features of materials, from crystal growth to mechanical properties.
      However, despite theoretical predictions, the detailed structure of dislocations
      remains largely elusive. By using a model system of tip-labeled rod-shaped
      particles enabling improved resolution and contrast by optical microscopy, in
      situ visualization and quantitative characterization of elementary dislocations
      has been performed at the lattice periodicity level in a colloidal smectic phase.
      Thanks to the micrometer layer spacing, the displacement field around an edge
      dislocation has been experimentally established and compared with the profile
      predicted by elastic theory. The local morphology of screw dislocations has also
      been evidenced, with the determination of the core size as well as the chiral
      handedness of the defect. Self-diffusion experiments performed at the individual
      particle level reveal for the first time nematiclike or "melted" ordering of the
      defect core.

PMID- 30230878
TI  - Effect of Cosmic Rays on the Evolution and Momentum Deposition of Supernova
      Remnants.
AB  - Using a semianalytical approach based on the thin-shell approximation, we
      calculate the long-term evolution of supernova remnants (SNRs) while also
      accounting for the cosmic rays (CRs) accelerated at their blast waves. Our
      solution reproduces the results of state-of-the-art fluid simulations across the
      adiabatic and radiative stages for the gas-only case, and it predicts that
      typical CR acceleration efficiencies (~10%) can boost SNR momentum deposition by
      a factor of 2-3. This enhancement can become as large as an order of magnitude in
      environments in which the gas experiences more severe radiative losses. This
      result may have a crucial impact on modeling the effect of supernova feedback on
      star formation and galaxy evolution.

PMID- 30230880
TI  - Ultrafast Modification of Hubbard U in a Strongly Correlated Material: Ab initio
      High-Harmonic Generation in NiO.
AB  - Engineering effective electronic parameters is a major focus in condensed matter
      physics. Their dynamical modulation opens the possibility of creating and
      controlling physical properties in systems driven out of equilibrium. In this
      Letter, we demonstrate that the Hubbard U, the widely used on-site Coulomb
      repulsion in strongly correlated materials, can be modified on femtosecond
      timescales by a strong nonresonant laser pulse excitation in the prototypical
      charge-transfer insulator NiO. Using our recently developed time-dependent
      density-functional theory plus self-consistent U method, we demonstrate the
      importance of a dynamically modulated U in the description of the high-harmonic
      generation of NiO. Our study opens the door to novel ways of modifying effective
      interactions in strongly correlated materials via laser driving, which may lead
      to new control paradigms for field-induced phase transitions and perhaps laser
      induced Mott insulation in charge-transfer materials.

PMID- 30230879
TI  - Edge Modes and Asymmetric Wave Transport in Topological Lattices: Experimental
      Characterization at Finite Frequencies.
AB  - Although topological mechanical metamaterials have been extensively studied from
      a theoretical perspective, their experimental characterization has been lagging.
      To address this shortcoming, we present a systematic, laser-assisted experimental
      characterization of topological kagome lattices, aimed at elucidating their in
      plane phononic and topological characteristics. We specifically explore the
      continuum elasticity limit, which is established when the ideal hinges that
      appear in the theoretical models are replaced by ligaments capable of supporting
      bending deformation, as observed for instance in realistic physical lattices. We
      reveal how the zero-energy floppy edge modes predicted for ideal configurations
      morph into finite-frequency phonon modes that localize at the edges. By probing
      the lattices with carefully designed excitation signals, we are able to extract
      and characterize all the features of a complex, low-frequency acoustic regime in
      which bulk modes and topological edge modes overlap and entangle in response. The
      experiments provide unequivocal evidence of the existence of strong asymmetric
      wave transport regimes at finite frequencies.

PMID- 30230881
TI  - Modulation Instability Induced Frequency Comb Generation in a Continuously Pumped
      Optical Parametric Oscillator.
AB  - Continuously pumped passive nonlinear cavities can be harnessed for the creation
      of novel optical frequency combs. While most research has focused on third-order
      "Kerr" nonlinear interactions, recent studies have shown that frequency comb
      formation can also occur via second-order nonlinear effects. Here, we report on
      the formation of quadratic combs in optical parametric oscillator (OPO)
      configurations. Specifically, we demonstrate that optical frequency combs can be
      generated in the parametric region around half of the pump frequency in a
      continuously driven OPO. We also model the OPO dynamics through a single time
      domain mean-field equation, identifying previously unknown dynamical regimes,
      induced by modulation instabilities, which lead to comb formation. Numerical
      simulation results are in good agreement with experimentally observed spectra.
      Moreover, the analysis of the coherence properties of the simulated spectra shows
      the existence of correlated and phase-locked combs. Our results reveal previously
      unnoticed dynamics of an apparently well assessed optical system, and can lead to
      a new class of frequency comb sources that may stimulate novel applications by
      enabling straightforward access to elusive spectral regions, such as the
      midinfrared.

PMID- 30230882
TI  - High-Sensitivity rf Spectroscopy of a Strongly Interacting Fermi Gas.
AB  - rf spectroscopy is one of the most powerful probing techniques in the field of
      ultracold gases. We report on a novel rf spectroscopy scheme with which we can
      detect very weak signals of only a few atoms. Using this method, we extended the
      experimentally accessible photon-energies range by an order of magnitude compared
      to previous studies. We directly verify a universal property of fermions with
      short-range interactions which is a power-law scaling of the rf spectrum tail all
      the way up to the interaction scale. We also determine, with high precision, the
      trap average contact parameter for different interaction strength. Finally, we
      employ our technique to precisely measure the binding energy of Feshbach
      molecules in an extended range of magnetic fields. These data are used to extract
      a new calibration of the Feshbach resonance between the two lowest energy levels
      of ^{40}K.

PMID- 30230883
TI  - Localization Transition for Light Scattering by Cold Atoms in an External
      Magnetic Field.
AB  - We establish a localization phase diagram for light in a random three-dimensional
      (3D) ensemble of motionless two-level atoms with a threefold degenerate upper
      level, in a strong static magnetic field. Localized modes appear in a narrow
      spectral band when the number density of atoms rho exceeds a critical value
      rho_{c}?0.1k_{0}^{3}, where k_{0} is the wave number of light in the free space.
      A critical exponent of the localization transition taking place upon varying the
      frequency of light at a constant rho>rho_{c} is estimated to be nu=1.57+/-0.07.
      This classifies the transition as an Anderson localization transition of 3D
      orthogonal universality class.

PMID- 30230884
TI  - Indefinite Causal Order in a Quantum Switch.
AB  - Quantum mechanics allows events to happen with no definite causal order: this can
      be verified by measuring a causal witness, in the same way that an entanglement
      witness verifies entanglement. Here, we realize a photonic quantum switch, where
      two operations A[over ^] and B[over ^] act in a quantum superposition of their
      two possible orders. The operations are on the transverse spatial mode of the
      photons; polarization coherently controls their order. Our implementation ensures
      that the operations cannot be distinguished by spatial or temporal position
      further it allows qudit encoding in the target. We confirm our quantum switch has
      no definite causal order by constructing a causal witness and measuring its value
      to be 18 standard deviations beyond the definite-order bound.

PMID- 30230885
TI  - Frequency- and Amplitude-Dependent Microbial Population Dynamics during Cycles of
      Feast and Famine.
AB  - In nature microbial populations are subject to fluctuating nutrient levels.
      Nutrient fluctuations are important for evolutionary and ecological dynamics in
      microbial communities since they impact growth rates, population sizes, and
      biofilm formation. Here we use automated continuous-culture devices and high
      throughput imaging to show that when populations of Escherichia coli are
      subjected to cycles of nutrient excess (feasts) and scarcity (famine) their
      abundance dynamics during famines depend on the frequency and amplitude of
      feasts. We show that frequency and amplitude dependent dynamics in planktonic
      populations arise from nutrient and history dependent rates of aggregation and
      dispersal. A phenomenological model recapitulates our experimental observations.
      Our results show that the statistical properties of environmental fluctuations
      have substantial impacts on spatial structure in bacterial populations driving
      large changes in abundance dynamics.

PMID- 30230886
TI  - Strongly Correlated Bosons on a Dynamical Lattice.
AB  - We study a one-dimensional system of strongly correlated bosons on a dynamical
      lattice. To this end, we extend the standard Bose-Hubbard Hamiltonian to include
      extra degrees of freedom on the bonds of the lattice. We show that this minimal
      model exhibits phenomena reminiscent of fermion-phonon models. In particular, we
      discover a bosonic analog of the Peierls transition, where the translational
      symmetry of the underlying lattice is spontaneously broken. This provides a
      dynamical mechanism to obtain a topological insulator in the presence of
      interactions, analogous to the Su-Schrieffer-Heeger model for electrons. We
      characterize the phase diagram numerically, showing different types of bond order
      waves and topological solitons. Finally, we study the possibility of implementing
      the model using atomic systems.

PMID- 30230887
TI  - Cavity Formation in Confined Growing Crystals.
AB  - Growing crystals form a cavity when placed against a wall. The birth of the
      cavity is observed both by optical microscopy of sodium chlorate crystals
      (NaClO_{3}) growing in the vicinity of a glass surface, and in simulations with a
      thin film model. The cavity appears when growth cannot be maintained in the
      center of the contact region due to an insufficient supply of growth units
      through the liquid film between the crystal and the wall. We obtain a
      nonequilibrium morphology diagram characterizing the conditions under which a
      cavity appears. Cavity formation is a generic phenomenon at the origin of the
      formation of growth rims observed in many experiments, and is a source of
      complexity for the morphology of growing crystals in natural environments. Our
      results also provide restrictions for the conditions under which compact crystals
      can grow in confinement.

PMID- 30230851
TI  - Measurement of Angular and CP Asymmetries in D^{0}->pi^{+}pi^{-}MU^{+}MU^{-} and
      D^{0}->K^{+}K^{-}MU^{+}MU^{-} Decays.
AB  - The first measurements of the forward-backward asymmetry of the dimuon pair
      (A_{FB}), the triple-product asymmetry (A_{2phi}), and the charge-parity
      conjugation asymmetry (A_{CP}), in D^{0}->pi^{+}pi^{-}MU^{+}MU^{-} and D^{0}
      >K^{+}K^{-}MU^{+}MU^{-} decays are reported. They are performed using data from
      proton-proton collisions collected with the LHCb experiment from 2011 to 2016,
      corresponding to a total integrated luminosity of 5  fb^{-1}. The asymmetries are
      measured to be A_{FB}(D^{0}->pi^{+}pi^{-}MU^{+}MU^{-})=(3.3+/-3.7+/-0.6)%,
      A_{2phi}(D^{0}->pi^{+}pi^{-}MU^{+}MU^{-})=(-0.6+/-3.7+/-0.6)%, A_{CP}(D^{0}
      >pi^{+}pi^{-}MU^{+}MU^{-})=(4.9+/-3.8+/-0.7)%, A_{FB}(D^{0}->K^{+}K^{-}MU^{+}MU^{
      })=(0+/-11+/-2)%, A_{2phi}(D^{0}->K^{+}K^{-}MU^{+}MU^{-})=(9+/-11+/-1)%,
      A_{CP}(D^{0}->K^{+}K^{-}MU^{+}MU^{-})=(0+/-11+/-2)%, where the first uncertainty
      is statistical and the second systematic. The asymmetries are also measured as a
      function of the dimuon invariant mass. The results are consistent with the
      standard model predictions.

PMID- 30230888
TI  - Hectometer Revivals of Quantum Interference.
AB  - Cavity-enhanced single photon sources exhibit mode-locked biphoton states with
      comblike correlation functions. Our ultrabright source additionally emits single
      photon pairs as well as two-photon NOON states, dividing the output into an even
      and an odd comb, respectively. With even-comb photons we demonstrate revivals of
      the typical nonclassical Hong-Ou-Mandel interference up to the 84th dip,
      corresponding to a path length difference exceeding 100 m. With odd-comb photons
      we observe single photon interference fringes modulated over twice the
      displacement range of the Hong-Ou-Mandel interference.

PMID- 30230891
TI  - Weak-link Josephson Junctions Made from Topological Crystalline Insulators.
AB  - We report on the fabrication of Josephson junctions using the topological
      crystalline insulator Pb_{0.5}Sn_{0.5}Te as the weak link. The properties of
      these junctions are characterized and compared to those fabricated with weak
      links of PbTe, a similar material yet topologically trivial. Most striking is the
      difference in the ac Josephson effect: junctions made with Pb_{0.5}Sn_{0.5}Te
      exhibit a rich subharmonic structure consistent with a skewed current-phase
      relation. This structure is absent in junctions fabricated from PbTe. A
      discussion is given on the origin of this effect as an indication of novel
      behavior arising from the topologically nontrivial surface state.

PMID- 30230892
TI  - Quasiparticles in Quantum Spin Chains with Long-Range Interactions.
AB  - We study quasiparticle excitations for quantum spin chains with long-range
      interactions using variational matrix product state techniques. It is confirmed
      that the local quasiparticle ansatz is able to capture those excitations very
      accurately, even when the correlation length becomes very large and in the case
      of topological nontrivial excitation such as spinons. It is demonstrated that the
      breaking of the Lieb-Robinson bound follows from the appearance of cusps in the
      dispersion relation, and evidence is given for a crossover between different
      quasiparticles as the long-range interactions are tuned.

PMID- 30230890
TI  - Twin-Image-Free Holography: A Compressive Sensing Approach.
AB  - Holographic reconstruction is troubled by the phase-conjugate wave front arising
      from Hermitian symmetry of the complex field. The so-called twin image obfuscates
      the reconstruction in solving the inverse problem. Here we quantitatively reveal
      how and how much the twin image affects the reconstruction and propose a
      compressive sensing (CS) approach to reconstruct a hologram completely free from
      the twin image. Using the canonical basis, the incoherence condition of CS is
      naturally satisfied by the Fourier transformation associated with wave
      propagation. With the propagation kernel function related to the distance, the
      object wave diffracts into a sharp pattern while the phase-conjugate wave
      diffracts into a diffuse pattern. An iterative algorithm using a total variation
      sparsity constraint could filter out the diffuse conjugated signal and overcome
      the inherent physical symmetry of holographic reconstruction. The feasibility is
      verified by simulation and experimental results, as well as a comparative study
      to an existing phase retrieval method.

PMID- 30230894
TI  - Experimental Constraint on an Exotic Spin- and Velocity-Dependent Interaction in
      the Sub-meV Range of Axion Mass with a Spin-Exchange Relaxation-Free
      Magnetometer.
AB  - We conducted a search for an exotic spin- and velocity-dependent interaction for
      polarized electrons with an experimental approach based on a high-sensitivity
      spin-exchange relaxation-free (SERF) magnetometer, which serves as both a source
      of polarized electrons and a magnetic-field sensor. The experiment aims to
      sensitively detect magnetic-fieldlike effects from the exotic interaction between
      the polarized electrons in a SERF vapor cell and unpolarized nucleons of a
      closely located solid-state mass. We report experimental results on the
      interaction with 82 h of data averaging, which sets an experimental limit on the
      coupling strength around 10^{-19} for the axion mass m_{a}?10^{-3}  eV, within
      the important axion window.

PMID- 30230893
TI  - Developing an Experimental Basis for Understanding Transport in NIF Hohlraum
      Plasmas.
AB  - We report on the first multilocation electron temperature (T_{e}) and flow
      measurements in an ignition hohlraum at the National Ignition Facility using the
      novel technique of mid-Z spectroscopic tracer "dots." The measurements define a
      low resolution "map" of hohlraum plasma conditions and provide a basis for the
      first multilocation tests of particle and energy transport physics in a laser
      driven x-ray cavity. The data set is consistent with classical heat flow near the
      capsule but reduced heat flow near the laser entrance hole. We evaluate the role
      of kinetic effects, self-generated magnetic fields, and instabilities in causing
      spatially dependent heat transport in the hohlraum.

PMID- 30230897
TI  - Effects of Lifshitz Transitions in Ferromagnetic Superconductors: The Case of
      URhGe.
AB  - In ferromagnetic superconductors, like URhGe, superconductivity coexists with
      magnetism near zero field, but then reappears in a finite field range, where the
      system also displays mass enhancement in the normal state. We present the
      theoretical understanding of this nonmonotonic behavior. We explore the multiband
      nature of URhGe and associate reentrant superconductivity and mass enhancement
      with the topological transition (Lifshitz) in one of the bands in a finite
      magnetic field. We find excellent agreement between our theory and a number of
      experimental results for URhGe, such as weakly first-order reentrant transition,
      the dependence of superconducting T_{c} on a magnetic field, and the field
      dependence of the effective mass, the specific heat, and the resistivity in the
      normal state. Our theory can be applied to other ferromagnetic multiband
      superconductors.

PMID- 30230898
TI  - Monogamy of Particle Statistics in Tripartite Systems Simulating Bosons and
      Fermions.
AB  - In the quantum world, correlations can take the form of entanglement which is
      known to be monogamous. In this Letter we show that another type of correlation,
      indistinguishability, is also restricted by some form of monogamy. Namely, if
      particles A and B simulate bosons, then A and C cannot perfectly imitate
      fermions. Our main result consists in demonstrating to what extent it is
      possible.

PMID- 30230896
TI  - Spin Thermal Hall Conductivity of a Kagome Antiferromagnet.
AB  - A clear thermal Hall signal (kappa_{xy}) was observed in the spin-liquid phase of
      the S=1/2 kagome antiferromagnet Ca kapellasite
      [CaCu_{3}(OH)_{6}Cl_{2}.0.6H_{2}O]. We found that kappa_{xy} is well reproduced,
      both qualitatively and quantitatively, using the Schwinger-boson mean-field
      theory with the Dzyaloshinskii-Moriya interaction of D/J~0.1. In particular,
      kappa_{xy} values of Ca kapellasite and those of another kagome antiferromagnet,
      volborthite, converge to one single curve in simulations modeled using Schwinger
      bosons, indicating a common temperature dependence of kappa_{xy} for the spins of
      a kagome antiferromagnet.

PMID- 30230899
TI  - Arcsine Laws in Stochastic Thermodynamics.
AB  - We show that the fraction of time that a thermodynamic current spends above its
      average value follows the arcsine law, a prominent result obtained by Levy for
      Brownian motion. Stochastic currents with long streaks above or below their
      average are much more likely than those that spend similar fractions of time
      above and below their average. Our result is confirmed with experimental data
      from a Brownian Carnot engine. We also conjecture that two other random times
      associated with currents obey the arcsine law: the time a current reaches its
      maximum value and the last time a current crosses its average value. These
      results apply to, inter alia, molecular motors, quantum dots, and colloidal
      systems.

PMID- 30230900
TI  - Laser-Based Metastable Krypton Generation.
AB  - We demonstrate the generation of metastable krypton in the long-lived 1s^{5}
      state using laser excitation. The atoms are excited through a two-photon
      absorption process into the 2p^{6} state using a pulsed optical parametric
      oscillator laser operating near 215 nm, after which the atoms decay quickly into
      the metastable state with a branching ratio of 75%. The interaction dynamics are
      modeled using density matrix formalism and, by combining this with experimental
      observations, we are able to calculate photoionization and two-photon absorption
      cross sections. When compared to traditional approaches to metastable production,
      this approach shows great potential for high-density metastable krypton
      production with minimal heating of the sample. Here, we show metastable
      production efficiencies of up to 2% per pulse. The new experimental results
      gained here, when combined with the density matrix model we have developed,
      suggest that fractional efficiencies up to 30% are possible under optimal
      conditions.

PMID- 30230901
TI  - Magnetosensitivity in Dipolarly Coupled Three-Spin Systems.
AB  - The radical pair mechanism is a canonical model for the magnetosensitivity of
      chemical reaction processes. The key ingredient of this model is the hyperfine
      interaction that induces a coherent mixing of singlet and triplet electron spin
      states in pairs of radicals, thereby facilitating magnetic field effects (MFEs)
      on reaction yields through spin-selective reaction channels. We show that the
      hyperfine interaction is not a categorical requirement to realize the sensitivity
      of radical reactions to weak magnetic fields. We propose that, in systems
      comprising three instead of two radicals, dipolar interactions provide an
      alternative pathway for MFEs. By considering the role of symmetries and energy
      level crossings, we present a model that demonstrates a directional sensitivity
      to fields weaker than the geomagnetic field and remarkable spikes in the reaction
      yield as a function of the magnetic field intensity; these effects can moreover
      be tuned by the exchange interaction. Our results further the current
      understanding of the effects of weak magnetic fields on chemical reactions, could
      pave the way to a clearer understanding of the mysteries of magnetoreception and
      other biological MFEs and motivate the design of quantum sensors. Further still,
      this phenomenon will affect spin systems used in quantum information processing
      in the solid state and may also be applicable to spintronics.

PMID- 30230902
TI  - Spatial-Translation-Induced Discrete Time Crystals.
AB  - A discrete time crystal is a phase unique to nonequilibrium systems, where
      discrete time translation symmetry is spontaneously broken. Most conventional
      time crystals proposed so far rely on the spontaneous breaking of on-site
      symmetries and their corresponding on-site symmetry operations. In this Letter,
      we propose a new time crystal dubbed the "spatial-translation-induced discrete
      time crystal," which is realized by spatial translation and its symmetry
      breaking. Owing to the properties of spatial translation, in this new time
      crystal, various time crystal orders can only emerge by changing the filling but
      not changing the driving protocol. We demonstrate that the local transport of
      charges or spins shows a nontrivial oscillation, enabling detection and
      applications of time crystal orders, and also provide promising platforms
      including quantum circuits. Our proposal opens up a new avenue of realizing time
      crystal orders by spatial translation in various quantum simulators.

PMID- 30230904
TI  - Emergent SU(4) Symmetry in alpha-ZrCl_{3} and Crystalline Spin-Orbital Liquids.
AB  - While the enhancement of spin-space symmetry from the usual SU(2) to SU(N) is
      promising for finding nontrivial quantum spin liquids, its realization in
      magnetic materials remains challenging. Here, we propose a new mechanism by which
      SU(4) symmetry emerges in the strong spin-orbit coupling limit. In d^{1}
      transition metal compounds with edge-sharing anion octahedra, the spin-orbit
      coupling gives rise to strongly bond-dependent and apparently SU(4)-breaking
      hopping between the J_{eff}=3/2 quartets. However, in the honeycomb structure, a
      gauge transformation maps the system to an SU(4)-symmetric Hubbard model. In the
      strong repulsion limit at quarter filling, as realized in alpha-ZrCl_{3}, the low
      energy effective model is the SU(4) Heisenberg model on the honeycomb lattice,
      which cannot have a trivial gapped ground state and is expected to host a gapless
      spin-orbital liquid. By generalizing this model to other three-dimensional
      lattices, we also propose crystalline spin-orbital liquids protected by this
      emergent SU(4) symmetry and space group symmetries.

PMID- 30230907
TI  - Topology of One-Dimensional Quantum Systems Out of Equilibrium.
AB  - We study the topological properties of one-dimensional systems undergoing unitary
      time evolution. We show that symmetries possessed both by the initial wave
      function and by the Hamiltonian at all times may not be present in the time
      dependent wave function-a phenomenon which we dub "dynamically induced symmetry
      breaking." This leads to the possibility of a time-varying bulk index after
      quenching within noninteracting gapped topological phases. The consequences are
      observable experimentally through particle transport measurements. With reference
      to the entanglement spectrum, we explain how the topology of the wave function
      can change out of equilibrium, both for noninteracting fermions and for symmetry
      protected topological phases protected by antiunitary symmetries.

PMID- 30230905
TI  - Realization of a Strongly Interacting Fermi Gas of Dipolar Atoms.
AB  - We realize a two-component dipolar Fermi gas with tunable interactions, using
      erbium atoms. Employing a lattice-protection technique, we selectively prepare
      deeply degenerate mixtures of the two lowest spin states and perform high
      resolution Feshbach spectroscopy in an optical dipole trap. We identify a
      comparatively broad Feshbach resonance and map the interspin scattering length in
      its vicinity. The Fermi mixture shows a remarkable collisional stability in the
      strongly interacting regime, providing a first step towards studies of superfluid
      pairing, crossing from Cooper pairs to bound molecules, in presence of dipole
      dipole interactions.

PMID- 30230908
TI  - Topological Transitions Induced by Antiferromagnetism in a Thin-Film Topological
      Insulator.
AB  - Magnetism in topological insulators (TIs) opens a topologically nontrivial
      exchange band gap, providing an exciting platform for manipulating the
      topological order through an external magnetic field. Here, we show that the
      surface of an antiferromagnetic thin film can magnetize the top and the bottom TI
      surface states through interfacial couplings. During the magnetization reversal,
      intermediate spin configurations are ascribed from unsynchronized magnetic
      switchings. This unsynchronized switching develops antisymmetric
      magnetoresistance spikes during magnetization reversals, which might originate
      from a series of topological transitions. With the high Neel ordering temperature
      provided by the antiferromagnetic layers, the signature of the induced
      topological transition persists up to ~90  K.

PMID- 30230909
TI  - Clinical Significance of Upper Airway Virus Detection in Critically Ill
      Hematology Patients.
AB  - RATIONALE: Noninvasive diagnostic tests can ensure the early identification and
      treatment of viral infections in patients with hematological malignancies.
      OBJECTIVES: To assess the clinical relevance of a positive virus PCR test on
      nasal swabs in critically ill hematology patients Methods: Post-hoc analysis of a
      prospective cohort of critically ill hematology patients admitted to 17 ICUs.
      Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR
      assay. Predictors of ICU mortality and assay positivity were identified.
      MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory
      failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and
      30.7% influenza/parainfluenza [PIV]/respiratory syncytial viruses [RSV]). Overall
      ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity
      was associated with lymphoproliferative disorders, hematopoietic stem cell
      transplantation, treatment with steroids or other immunosuppressants, ARF (25.5%
      vs. 16.3%, P=0.004), and death in the ICU (28.9% vs. 19.3%, P=0.008). The
      association with ICU mortality was significant for all viruses and was strongest
      for influenza/PIV/RSV. In patients with ARF, detection of any respiratory virus
      was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence
      interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper
      airway by multiplex PCR assay is common in critically ill hematology patients. In
      patients with ARF, respiratory virus detection was independently associated with
      ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification
      of hematology patients with ARF. Studies to understand whether respiratory tract
      viruses play a causal role in outcomes are warranted.

PMID- 30230910
TI  - Pitching Performance After Ulnar Collateral Ligament Reconstruction at a Single
      Institution in Major League Baseball Pitchers.
AB  - BACKGROUND:: Ulnar collateral ligament (UCL) reconstruction (UCLR) has shown
      reliable rates of return to play, with conflicting results on pitching
      performance after players' return. PURPOSE:: To evaluate Major League Baseball
      (MLB) pitching performance before and after UCLR performed at a single
      institution. STUDY DESIGN:: Cohort study; Level of evidence, 3. METHODS:: MLB
      pitchers (minor league players were excluded) who underwent UCLR at our
      institution between 2002 and 2016 were identified. Player information and return
      to play were determined including pitching level (MLB vs minor league) and total
      number of years played after surgery. Pitching performance statistics were
      evaluated for 3 years before surgery and for 3 years after returning to play
      including earned run average (ERA), walks plus hits per inning pitched (WHIP),
      innings pitched, wins above replacement, runs above replacement, and pitch
      velocity. RESULTS:: A total of 54 MLB pitchers were identified, with 46 primary
      and 8 revision reconstructions. The mean time to return to play was 13.8 months
      (primary reconstruction: 13.7 months). The majority returned to play with a 94%
      return rate (primary reconstruction: 96%), and 80% returned to MLB play (primary
      reconstruction: 82%). Three primary reconstructions required revision surgery.
      Pitchers played a mean of 3.2 years in MLB and 4.6 years total after surgery (39%
      still playing). Pitching workload and performance were maintained or improved
      after surgery. The preoperative ERA was 4.63 versus 4.13 after returning to play
      ( P = .268). Fastball velocity ( P = .032), ERA ( P = .003), and WHIP ( P = .001)
      worsened the first year after surgery and then improved the second year (ERA:
      4.63 to 4.06 [ P = .380]; WHIP: 1.35 to 1.32 [ P = .221]; fastball velocity: 91.3
      to 91.9 mph [ P = .097]). Compared with a matched control group, pitchers who had
      UCLR showed improvements or maintained performance after reconstruction including
      improved ERA ( P = .007), WHIP ( P = .025), and fastball velocity ( P = .006).
      CONCLUSION:: MLB players experienced a high rate of return to play and previous
      level of play after UCLR. Pitching workload was maintained after returning to
      play. Pitching performance initially decreased the first year after returning and
      then improved or reverted to previous levels after the first year from UCLR.

PMID- 30230906
TI  - Characterizing the Analogy Between Hyperbolic Embedding and Community Structure
      of Complex Networks.
AB  - We show that the community structure of a network can be used as a coarse version
      of its embedding in a hidden space with hyperbolic geometry. The finding emerges
      from a systematic analysis of several real-world and synthetic networks. We take
      advantage of the analogy for reinterpreting results originally obtained through
      network hyperbolic embedding in terms of community structure only. First, we show
      that the robustness of a multiplex network can be controlled by tuning the
      correlation between the community structures across different layers. Second, we
      deploy an efficient greedy protocol for network navigability that makes use of
      routing tables based on community structure.

PMID- 30230911
TI  - Characterization and sequence analysis of potential biofertilizer and biocontrol
      agent Bacillus subtilis strain SEM-9 from silkworm excrement.
AB  - Fusarium wilt is a devastating soil-borne disease caused mainly by highly host
      specific formae speciales of Fusarium oxysporum. Antagonistic microorganisms play
      a very important role in Fusarium wilt control, and the isolation of potential
      biocontrol strains is becoming more and more important. We isolated a bacterial
      strain (SEM-9) from the high-temperature stage of silkworm excrement composting,
      which had a marked ability to solubilize phosphorus, promote the growth and
      increase the yield of the small Chinese cabbage, and which also exhibited
      considerable antagonistic effect towards Fusarium sambucinum and other fungi. The
      result of physiological and biochemical analyses, as well as genome sequencing,
      showed that SEM-9 was a strain of Bacillus subtilis. Through genome annotation
      and analysis, it was found that SEM-9 contained genes related to the regulation
      of biofilm formation, which may play an important role in colonization, and gene
      clusters encoding the biosynthesis of antimicrobials, such as surfactin,
      bacilysin, fengycin, and subtilosin-A. The production of such antifungal
      compounds may constitute the basis of the mode-of-action of SEM-9 against
      Fusarium spp. These data suggested that the SEM-9 strain has potential as both a
      biofertilizer and a biocontrol agent, with the potential to manage Fusarium wilt
      disease in crops.

PMID- 30230913
TI  - Night work effects on salivary cytokines TNF, IL-1beta and IL-6.
AB  - Shift work is unavoidable in modern societies, but at the same time disrupts
      biological rhythms and contributes to social distress and disturbance of sleep,
      health and well-being of shift workers. Shift work has been associated with some
      chronic diseases in which a chronic inflammatory condition may play a role.
      However, few studies investigating the association of cytokine and other
      inflammation markers with shift workers have been published in recent years. In
      this study we evaluated the effects of permanent night work on the production of
      tumor necrosis factor (TNF), interleukin-1beta (IL-1beta), IL-6 and melatonin in
      saliva. Another aim was to demonstrate the benefit of the use of salivary
      cytokines for studies in chronobiology, since it is an easy and non-invasive
      method that allows for sampling at several times. Thirty-eight healthy male
      workers, being 21 day workers and 17 night workers, agreed to participate in this
      study. Sleep was evaluated by actigraphy and activity protocols. Saliva was
      collected during three workdays approximately at the middle of the work shift and
      at bed and wake times of the main sleep episode. Saliva samples were then
      analyzed by enzyme-linked immunosorbent assay to measure TNF, IL-1beta, IL-6 and
      melatonin levels, and the results were submitted to non-parametric statistical
      analysis. The use of saliva instead of blood allowed for a greater number of
      samples from the same subjects, allowing identifying alterations in the daily
      production patterns of salivary cytokines TNF, IL-1beta and IL-6 that probably
      are linked to night work. Salivary TNF and IL-1beta levels were similar for day
      and night workers, with higher daily production after awakening, in the morning
      hours for day workers and in the afternoon for night workers. Both groups
      presented a significant daily variation pattern of these two cytokines. Day and
      night workers produced similar amounts of salivary IL-6. Nevertheless, the daily
      variation pattern observed among day workers, with a peak after awakening, was
      absent among night workers. Thus, in our study, night workers showed partially
      adjusted daily variation patterns for salivary TNF and IL-1beta, not seen for
      salivary IL-6. Results for salivary IL-6 could be better explained as a
      consequence of circadian disruption due to permanent night work. Our results
      suggest that the whole circadian system, including clocks and pineal gland, is
      involved in regulating cytokine profile in shift workers and that a coordinated
      production of these cytokines, important for an adequate inflammatory response,
      could be disturbed by shift work. The distinct effects that shift work may have
      on different cytokines could give some cues about the mechanisms involved in this
      association.

PMID- 30230912
TI  - Concussion History and Cognitive Function in a Large Cohort of Adolescent
      Athletes.
AB  - BACKGROUND:: The incidence of reported concussions in the adolescent population
      is increasing, yet research on the effects of concussions in this population is
      minimal and inconclusive. PURPOSE:: To assess the association between concussion
      and performance on a cognitive test battery. STUDY DESIGN:: Cross-sectional
      study; Level of evidence, 3. METHODS:: Using multivariate models, the authors
      assessed the association between concussion and performance on a cognitive test
      battery among 5616 high school and junior high school athletes. The researchers
      utilized a global cognitive score and scores for 5 domains: verbal memory, visual
      memory, visual motor, reaction time, and impulse control. Each cognitive score
      was converted to a z score with the mean and SD of the nonconcussed population.
      Results from each model were then interpreted as change in the standardized unit
      score. In the models, concussion was evaluated as ever having a concussion,
      number of concussions, time since last concussion, and age at first concussion.
      RESULTS:: Ever having a concussion was associated with a mean decrease of 0.11
      standardized units (95% CI, -0.20 to -0.01) on the global cognitive score and
      lower scores in all cognitive domains. Each additional concussion was associated
      with lower scores on global cognitive function (effect estimate, -0.06; 95% CI, 
      0.11 to -0.02), verbal memory, visual memory, and impulse control. Concussion in
      early childhood was associated with lower global cognition (effect estimate, 
      0.05; 95% CI, -0.08 to -0.01), visual memory, and motor visual scores as compared
      with concussions in later childhood. The associations between time since last
      concussion and cognitive test scores were nonlinear, and on all tests, lower
      scores were observed even >=1 year after the concussion. CONCLUSION:: On the
      basis of objective performance metrics for cognitive function, concussions had a
      more persistent effect on cognitive function than previously thought. The age at
      which an individual has his or her first concussion may be an important factor in
      determining long-lasting cognitive effects.

PMID- 30230914
TI  - TGF-beta/Smads Signaling Affects Radiation Response and Prolongs Survival by
      Regulating DNA Repair Genes in Malignant Glioma.
AB  - To understand the molecular mechanism underlying the causal relationship between
      aberrant upregulation of transforming growth factor beta (TGF-beta) and radio
      resistance in glioma. The mouse glioma cell GL261 was irradiated, and relative
      expression of TGF-beta/Smad signaling genes was determined by real-time PCR and
      western blotting. The DNA repair response on exogenous TGF-beta or LY2109761 was
      evaluated by quantification of diverse genes by real-time PCR and western
      blotting. Xenograft mice were employed for in vivo investigation to assess the
      response to irradiation and LY2109761 either alone or in combination. The
      expression of DNA repair genes was further determined in the xenograft tumor. The
      TGF-beta/Smad signaling pathway was activated by radiation in the GL261 cell
      line. The exogenous complement of TGF-beta significantly stimulated DNA repair
      response. Administration of LY2109761 suppressed DNA repair genes. Simultaneous
      treatment with LY2109761 abrogated the upregulation of DNA repair genes in GL261.
      In the xenograft tumor model, LY2109761 synergistically improved the therapeutic
      effect of radiation via improvement of sensitivity. Our data suggested that
      LY2109761 treatment re-sensitized glioma to radiation via antagonizing TGF
      beta/Smad-induced DNA repair.

PMID- 30230917
TI  - Health Care Spending Under Employer-Sponsored Insurance: A 10-Year Retrospective.
AB  - Using a national sample of health care claims data from the Health Care Cost
      Institute, we found that total spending per capita (not including premiums) on
      health services for enrollees in employer-sponsored insurance plans increased by
      44 percent from 2007 through 2016 (average annual growth of 4.1 percent).
      Spending increased across all major categories of health services, although the
      increases were not uniform across years or categories. Growth rates for total per
      capita spending generally slowed after 2009 but increased between 2014 and 2016.
      Spending on outpatient services grew more quickly (average annual growth of 5.7
      percent) compared to spending on the other types of services. However, the
      overall distribution of spending across categories remained largely unchanged. In
      the context of the dramatic economic and policy events that have taken place
      since 2007-including the Great Recession, the Affordable Care Act, and numerous
      medical innovations-this assessment of ten-year spending trends provides insights
      into how the largest insured population in the US contributes to health care
      spending growth.

PMID- 30230916
TI  - Influence of study population definition on the effect of age on outcomes after
      blunt head trauma.
AB  - OBJECTIVES: The purpose of this study was to assess whether study population
      definition influences the effect of age on outcomes after blunt head trauma. We
      hypothesized that examining 'all comers' receiving head computerized tomography
      after blunt head trauma, fewer older individuals would meet Veterans
      Administration and Department of Defense (VA/DoD) criteria for traumatic brain
      injury (TBI), and would, therefore, display better outcomes than younger cohorts.
      However, restricting to participants meeting VA/DoD criteria for TBI, we
      hypothesized that older individuals would have worse outcomes. METHODS: Data from
      a recently completed prospective cohort study were analysed with age dichotomized
      at 65 years. Logistic regression modelling, controlled for potential confounders
      including head trauma severity, was estimated to measure the effect of age on
      functional recovery, post-concussion symptoms (PCS), and depressive symptoms at 1
      month post-TBI. RESULTS: Fewer older than younger individuals met VA/DoD criteria
      for TBI. Older individuals had better functional, PCS, and depressive outcomes at
      1 month. Restricting to those meeting VA/DoD criteria for TBI, older individuals
      continued to have better functional and PCS outcomes but had outcomes comparable
      to younger on depressive symptoms. CONCLUSIONS: Contrary to our hypothesis, there
      was a tendency for older adults to have better outcomes than younger, independent
      of the diagnostic criteria applied.

PMID- 30230915
TI  - Cardiac Fgf-16 Expression Supports Cardiomyocyte Survival and Increases
      Resistance to Doxorubicin Cytotoxicity.
AB  - The fibroblast growth factor (FGF) 16 gene is preferentially expressed by
      cardiomyocytes after birth with levels increasing into adulthood. Null mice and
      isolated heart studies suggest a role for FGF-16 in cardiac maintenance and
      survival, including increased resistance to doxorubicin (DOX)-induced injury. A
      single treatment with DOX was also shown to rapidly deplete endogenous rat FGF-16
      mRNA at 6 h in both adult heart and neonatal cardiomyocytes. However, the effect
      of DOX on rat cardiac function at the time of decreased FGF-16 gene expression
      and the effect of FGF-16 availability on cardiomyocyte survival, including in the
      context of acute DOX cytotoxicity, have not been reported. The objective was to
      assess the effect of acute (6 and 24 h) DOX treatment on cardiac function and the
      effects of FGF-16 small interfering RNA "knockdown," as well as adenoviral
      overexpression, in the context of acute DOX cytotoxicity, including cardiomyocyte
      survival and DOX efflux transport. A significant decrease in heart systolic
      function was detected by echocardiography in adult rats treated with 15 mg DOX/kg
      at 6 h; however, unlike FGF-16, there was no change in atrial natriuretic peptide
      transcript levels. Both systolic and diastolic dysfunctions were observed at 24
      h. In addition, specific FGF-16 "knockdown" in neonatal rat cardiomyocytes
      results in a significant increase in cell death. Conversely, adenoviral FGF-16
      overexpression was associated with a significant decrease in cardiomyocyte injury
      as a result of 1 MUM DOX treatment. A specific increase in efflux transporter
      gene expression and DOX efflux was also seen, which is consistent with a
      reduction in DOX cytotoxicity. Finally, the increased efflux and decreased DOX
      induced damage with FGF-16 overexpression were blunted by inhibition of FGF
      receptor signaling. These observations are consistent with FGF-16 serving as an
      endogenous cardiomyocyte survival factor, which may involve a positive effect on
      regulating efflux transport to reduce cardiotoxicity.

PMID- 30230918
TI  - A comparison between two retrospective alcohol consumption measures and the daily
      drinking diary method with university students.
AB  - BACKGROUND: There are two main categories of retrospective self-report alcohol
      consumption measures: summary and daily drinking. Time-efficient summary measures
      have been criticized for being less able to capture sporadic and unpatterned
      drinking. A novel retrospective summary measure, the Typical and Atypical
      Drinking Diary (TADD), may produce more precise estimates of alcohol consumption
      than the gold-standard daily measure, the Timeline Followback (TLFB). OBJECTIVE:
      To establish how accurately the TADD and TLFB retrospectively capture alcohol
      consumption compared to the Daily Drinking Diary (DDD) method. METHOD: Forty
      three university undergraduates (77% female) concurrently recorded their daily
      alcohol consumption for 28 consecutive days using daily drinking diaries.
      Participants then retrospectively estimated their alcohol consumption using both
      the TADD and TLFB 28 days following completion of the 28-day daily consumption
      period. RESULTS: When compared against the drinking data obtained from the DDD
      method, the TADD consistently produced accurate retrospective estimates of total
      alcohol consumption, number of drinking days, and number of heavy drinking
      episodes. Contrariwise, the TLFB significantly underestimated all aspects of
      drinking. Underreporting on the TLFB was hypothesized to be associated with
      social desirability bias. CONCLUSION: The TADD is a valid and reliable instrument
      for retrospectively measuring alcohol consumption and drinking variability in the
      university student population.

PMID- 30230919
TI  - Nucleosides block AICAR-stimulated activation of AMPK in skeletal muscle and
      cancer cells.
AB  - AMP-activated kinase (AMPK) is a major regulator of energy metabolism and a
      promising target for development of new treatments for type 2 diabetes and
      cancer. 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), an
      adenosine analogue, is a standard positive control for AMPK activation in cell
      based assays. Some broadly used cell culture media, such as MEMalpha, contain
      high concentrations of adenosine and other nucleosides. We determined whether
      such media alter AICAR action in skeletal muscle and cancer cells. In nucleoside
      free media, AICAR stimulated AMPK activation, increased glucose uptake and
      suppressed cell proliferation. Conversely, these effects were blunted or
      completely blocked in MEMalpha that contains nucleosides. Addition of adenosine
      or 2'-deoxyadenosine to nucleoside-free media also suppressed AICAR action.
      MEMalpha with nucleosides blocked AICAR-stimulated AMPK activation even in the
      presence of methotrexate, which normally markedly enhances AICAR action by
      reducing its intracellular clearance. Other common media components, such as
      vitamin B12, vitamin C and alpha-lipoic acid, had a minor modulatory effect on
      AICAR action. Our findings show that nucleoside-containing media, commonly used
      in AMPK research, block action of the most widely used pharmacological AMPK
      activator AICAR. Results of cell-based assays in which AICAR is used for AMPK
      activation therefore critically depend on media formulation. Furthermore, our
      findings highlight a role for extracellular nucleosides and nucleoside
      transporters in regulation of AMPK activation.

PMID- 30230895
TI  - Measurement of the Omega_{c}^{0} Baryon Lifetime.
AB  - We report a measurement of the lifetime of the Omega_{c}^{0} baryon using proton
      proton collision data at center-of-mass energies of 7 and 8 TeV, corresponding to
      an integrated luminosity of 3.0  fb^{-1} collected by the LHCb experiment. The
      sample consists of about 1000  Omega_{b}^{-}->Omega_{c}^{0}MU^{-}nu[over -]_{MU}X
      signal decays, where the Omega_{c}^{0} baryon is detected in the pK^{-}K^{
      }pi^{+} final state and X represents possible additional undetected particles in
      the decay. The Omega_{c}^{0} lifetime is measured to be tau_{Omega_{c}^{0}}=268+/
      24+/-10+/-2  fs, where the uncertainties are statistical, systematic, and from
      the uncertainty in the D^{+} lifetime, respectively. This value is nearly four
      times larger than, and inconsistent with, the current world-average value.

PMID- 30230920
TI  - Prescribing High-intensity Interval Exercise by RPE in Individuals with Type 2
      Diabetes: Metabolic and Hemodynamic Responses.
AB  - We tested the hypothesis that rating of perceived exertion (RPE) is a tool as
      efficient as heart rate (HR) response to cardiopulmonary exercise test (CPX) for
      prescribing and self-regulating high-intensity interval exercise (HIIE), and that
      metabolic and hemodynamic response to HIIE is superior than to continuous
      moderate-intensity exercise (MICE) in individuals with type 2 diabetes mellitus
      (T2DM). Eleven participants (age=52.3+/-3yr) underwent HIIE prescribed and self
      regulated by RPE (HIIERPE; 25 min), HIIE prescribed and regulated by individuals'
      HR response to CPX (HIIEHR; 25 min), MICE prescribed and self-regulated by RPE
      (30 min) and control (CON; 30 min of seated resting) intervention in random
      order. HR, blood pressure (BP), capillary glucose, endothelial reactivity and
      carotid-femoral pulse wave velocity (PWV) were assessed before, immediately after
      and 45 min after each intervention. Exercise HR, speed and distance were measured
      during exercise sessions. 24-h ambulatory BP was measured after each
      intervention. Exercise HR, speed and distance were similar between HIIERPE and
      HIIEHR. BP response was not different among HIIERPE, HIIEHR, and MICE. Capillary
      glycaemia reduction was greater (P < 0.05) after HIIERPE (48.6+/-9.6 mg/dL) and
      HIIEHR (47.2+/-9.5 mg/dL) than MICE (29.5+/-11.5 mg/dL). Reduction (P < 0.05) in
      24-h (6.7+/-2.2 mmHg) and tendency toward reduction (P = 0.06) in daytime
      systolic (7.0+/-2.5 mmHg) ambulatory BP were found only after HIIERPE. These
      results suggest that HIIE is superior to MICE for reducing glycaemia and
      ambulatory BP, and that the 6 to 20 RPE scale is an useful tool for prescribing
      and self-regulating HIIE in individuals with T2DM.

PMID- 30230923
TI  - Comparing the effect of intestinal bacteria from rabbit, pig, and chicken on
      inflammatory response in cultured rabbit crypt and villus.
AB  - Rabbit is susceptible to intestinal infection, which often results in severe
      inflammatory response. To investigate whether the special community structure of
      rabbit intestinal bacteria contributes to this susceptibility, we compared the
      inflammatory responses of isolated rabbit crypt and villus to heat-treated total
      bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig
      and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit
      ileum. The intestinal bacteria from rabbit induced higher expression of toll-like
      receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression
      was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but
      not by those of rabbit. The ileal bacteria from those three animals all increased
      the expression of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL
      6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also
      stimulated the expression of anti-inflammatory factors interferon beta (IFN-beta)
      and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a
      higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more
      expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a
      higher percentage of Lactobacillus in chicken ileum might result in more
      expressive anti-inflammatory factors.

PMID- 30230922
TI  - Signature-oriented investigation of the efficacy of multicomponent drugs against
      heart failure.
AB  - Increasing attention has been paid to the application of precision medicine in
      heart failure (HF), and biomarker-based personalized medical care has shown great
      progress in HF management. Additionally, multicomponent drugs represented by
      traditional Chinese medicine (TCM) are demonstrating safety and efficacy in the
      management of HF. However, the potential mechanism is unclear, and the ambiguous
      clinical locations of TCM remain a hindrance to its extensive application. To
      meet this requirement, a precise investigation on the efficacy of multicomponent
      drugs against HF using the signature biomarkers-oriented approach was developed
      and applied to a conventional drug for cardiac disease, YiXinShu (YXS). On the
      basis of in vitro and in vivo efficacy evaluation of YXS against HF, and with the
      aid of proteomics and network pharmacology approaches, specific signatures
      regulated by YXS against HF were identified. YXS may show distinctive treatment
      features for those HF patients showing the elevation of fatty acid-binding
      protein 3 and cytoskeleton-associated protein 5, as well as other classic HF
      biomarkers. This study provides the first precise investigation of the efficacy
      of multicomponent drugs against HF and offers a practicable and low-cost approach
      for personalized management of HF.-Wei, J., Guo, F., Zhang, M., Xian, M., Wang,
      T., Gao, J., Wu, H., Song, L., Zhang, Y., Li, D., Yang, H., Huang, L. Signature
      oriented investigation of the efficacy of multicomponent drugs against heart
      failure.

PMID- 30230924
TI  - Barriers to accurately assessing prescription opioid misuse on surveys.
AB  - Surveys are the leading method of gathering data on prevalence and correlates of
      prescription opioid misuse. As the opioid crisis continues in the United States,
      reliable data on misuse have become increasingly important as under- and
      overreporting is common. This perspective discusses six potential barriers to
      researchers accurately assessing opioid misuse on surveys. These barriers include
      lack of respondent drug knowledge, researchers not properly defining opioids for
      respondents, querying overall opioid misuse rather than misuse of specific
      opioids, varying terminology (e.g., of opioids and misuse), and lack of
      understanding of medical versus nonmedical use or misuse. Finally, a recent
      barrier is use of counterfeit or adulterated drugs that contain fentanyl, its
      analogs, or other new synthetic opioids, which can lead to underreporting of
      exposure. Survey researchers should consider such barriers when querying opioid
      misuse.

PMID- 30230921
TI  - Calmodulin regulates MGRN1-GP78 interaction mediated ubiquitin proteasomal
      degradation system.
AB  - The mechanism by which the endoplasmic reticulum (ER) ubiquitin ligases sense
      stress to potentiate their activity is poorly understood. GP78, an ER E3 ligase,
      is best known for its role in ER-associated protein degradation, although its
      activity is also linked to mitophagy, ER-mitochondria junctions, and MAPK
      signaling, thus highlighting the importance of understanding its regulation. In
      healthy cells, Mahogunin really interesting new gene (RING) finger 1 (MGRN1)
      interacts with GP78 and proteasomally degrades it to alleviate mitophagy. Here,
      we identify calmodulin (CaM) as the adapter protein that senses fluctuating
      cytosolic Ca2+ levels and modulates the Ca2+-dependent MGRN1-GP78 interactions.
      When stress elevates cytosolic Ca2+ levels in cultured and primary neuronal
      cells, CaM binds to both E3 ligases and inhibits their interaction. Molecular
      docking, simulation, and biophysical studies show that CaM interacts with both
      proteins with different affinities and binding modes. The physiological impact of
      this interaction switch manifests in the regulation of ER-associated protein
      degradation, ER-mitochondria junctions, and relative distribution of smooth ER
      and rough ER.-Mukherjee, R., Bhattacharya, A., Sau, A., Basu, S., Chakrabarti,
      S., Chakrabarti, O. Calmodulin regulates MGRN1-GP78 interaction mediated
      ubiquitin proteasomal degradation system.

PMID- 30230925
TI  - Left ventricular hypertrophy is associated with increased sirtuin level in newly
      diagnosed hypertensive patients.
AB  - BACKGROUND: Arterial hypertension is one of the leading causes of mortality and
      morbidity in general population. Sirtuin 1 (SIRT1) has diverse anti-inflammation,
      anti-oxidant, and anti-apopytosis effects on endothelium and is associated with
      endothelial aging and dysfunction. The objective of this study was to evaluate
      the relation of serum SIRT1 level with left ventricular hypertrophy (LVH) in
      newly diagnosed hypertensive patients. METHODS: One hundered and twenty-five
      consecutive, newly diagnosed hypertensive patients were divided into two groups
      with regard to presence of LVH and compared to 40 healthy control subjects. LVH
      was determined by transthoracic echocardiography using the cube formula. Serum
      SIRT1 level was analyzed with enzyme-linked immunosorbent assay. RESULTS: Serum
      SIRT1 level was significantly higher in patients with LVH compared to those
      without LVH (14.3 +/- 3.9 ng/ml vs. 7.9 +/- 3.6 ng/ml, P < 0.001) and healthy
      control subjects (14.3 +/- 3.9 ng/ml vs 6.6 +/- 2.0 ng/ml, P < 0.001).
      Multivariate logistic regression analysis revealed higher serum SIRT1 level
      independently predicted LVH in hypertensive patients (OR 1.50; 95% CI, 1.30-1.73;
      P < 0.001). Receiver-operating characteristic curve analysis demonstrated a
      cutoff value of 9.4 had a sensitivity of 90% and specificity of 74% for the
      prediction of LVH (AUC 0.885; 95% CI, 0.815-0.935; P < 0.0001). CONCLUSION: SIRT1
      was a powerful biomarker for predicting LVH in hypertensive patients.

PMID- 30230926
TI  - Antibacterial, Preservative, and Mutagenic Potential of Copaifera spp. Oleoresins
      Against Causative Agents of Foodborne Diseases.
AB  - Foodborne diseases (FBDs) are a serious public health concern worldwide. In this
      scenario, preservatives based on natural products, especially plants, have
      attracted researchers' attention because they offer potential antimicrobial
      action as well as reduced health impact. The genus Copaifera spp., which is
      native of tropical South America and West Africa, contains several species for
      which pharmacological activities, including antibacterial effects, have been
      described. On the basis of minimum inhibitory concentration (MIC), minimum
      bactericidal concentration (MBC), antibiofilm activity (inhibition and
      eradication), preservative capacity, and Ames test, we evaluated the
      antibacterial, preservative, and mutagenic potential of Copaifera spp. oleoresins
      against the causative agents of FBDs. The Copaifera duckei, Copaifera reticulata,
      Copaifera paupera, and Copaifera pubiflora oleoresins displayed promising MIC/MBC
      values-from 12.5 to 100 MUg/mL-against Staphylococcus aureus (American Type
      Culture Collection [ATCC] 29213), Listeria monocytogenes (ATCC 15313), and
      Bacillus cereus (ATCC 14579). C. duckei, C. reticulata, C. paupera, and C.
      pubiflora oleoresin concentrations ranging from 25 to 200 MUg/mL and from 100 to
      400 MUg/mL inhibited biofilm formation and eradicated biofilms, respectively. The
      oleoresins did not exert mutagenic effects and had superior food preservative
      action to sodium benzoate (positive control). In conclusion, Copaifera oleoresins
      exhibit potential antibacterial activity and are not mutagenic, which makes them
      a promising source to develop novel natural food preservatives to inhibit
      foodborne pathogens.

PMID- 30230927
TI  - Chemical Modifications in the Life of an mRNA Transcript.
AB  - Investigations over the past eight years of chemical modifications on messenger
      RNA (mRNA) have revealed a new level of posttranscriptional gene regulation in
      eukaryotes. Rapid progress in our understanding of these modifications,
      particularly, N6-methyladenosine (m6A), has revealed their roles throughout the
      life cycle of an mRNA transcript. m6A methylation provides a rapid mechanism for
      coordinated transcriptome processing and turnover that is important in embryonic
      development and cell differentiation. In response to cellular signals, m6A can
      also regulate the translation of specific pools of transcripts. These mechanisms
      can be hijacked in human diseases, including numerous cancers and viral
      infection. Beyond m6A, many other mRNA modifications have been mapped in the
      transcriptome, but much less is known about their biological functions. As
      methods continue to be developed, we will be able to study these modifications
      both more broadly and in greater depth, which will likely reveal a wealth of new
      RNA biology.

PMID- 30230929
TI  - President and Program Chair's Introduction.

PMID- 30230928
TI  - The Multiple Levels of Mitonuclear Coregulation.
AB  - Together, the nuclear and mitochondrial genomes encode the oxidative
      phosphorylation (OXPHOS) complexes that reside in the mitochondrial inner
      membrane and enable aerobic life. Mitochondria maintain their own genome that is
      expressed and regulated by factors distinct from their nuclear counterparts. For
      optimal function, the cell must ensure proper stoichiometric production of OXPHOS
      subunits by coordinating two physically separated and evolutionarily distinct
      gene expression systems. Here, we review our current understanding of mitonuclear
      coregulation primarily at the levels of transcription and translation.
      Additionally, we discuss other levels of coregulation that may exist but remain
      largely unexplored, including mRNA modification and stability and
      posttranslational protein degradation.

PMID- 30230930
TI  - The emergence of multiword utterances in children with Down syndrome.
AB  - Morphosyntax is one of the most impaired aspects of language development in
      children with Down syndrome. The present study aimed to assess the emergence of
      multiword utterances in this population. Sixteen Italian-speaking children with
      Down syndrome were followed from 36 to 48 months of age. Data derived from an
      analysis of their spontaneous productions showed that although the mean
      productivity of multiword utterances increased over the three time points (36, 42
      and 48 months), different growth patterns of early syntactic development could be
      identified: (1) null or marginal development; (2) a gradual increase in multiword
      production over time; (3) an increase in the production of more complex multiword
      utterances and a decrease or inverted U-shaped profile in the production of
      simpler multiword productions; (4) an inverted U-shaped profile in multiword
      productions. In addition, children showed an improvement in their ability to
      express different semantic functions by word combinations. Significant
      relationships were found between early syntactic skills and both the child's
      vocabulary size and developmental age. A better knowledge of the acquisition pace
      and content of word combinations could allow more effective rehabilitative
      treatment during the first steps of children's syntactic development.

PMID- 30230931
TI  - Atypical Perinuclear Anti-Neutrophil Cytoplasmic Antibodies in Ocular
      Inflammatory Diseases.
AB  - PURPOSE: To characterize the clinical features of patients with ocular
      inflammatory diseases (OID) who tested positive for atypical perinuclear anti
      neutrophil cytoplasmic antibodies (P-ANCA). METHODS: Retrospective case series of
      patients with OID seen at the Massachusetts Eye Research and Surgery Institute
      (MERSI) from April 2014 to April 2016. RESULTS: 813 patients were tested for ANCA
      with 34 patients (4%) being positive for atypical P-ANCA. Among those with
      positive atypical P-ANCA, the most frequent diagnoses were anterior uveitis in
      62% (n = 21) followed by scleritis in 20% (n = 7). Only one patient had an
      episode of recurrent disease flare-up. All but one patient, who had concomitant C
      ANCA seropositivity and granulomatosis with polyangiitis, had a favorable disease
      course with controlled inflammation using topical and/or systemic
      immunomodulatory therapy. CONCLUSION: In contrast to typical C-ANCA and P-ANCA,
      atypical P-ANCA seropositivity was not associated with severe vasculitis or poor
      prognosis in patients with the OID.

PMID- 30230932
TI  - Neuropathology as a consequence of neonatal ventilation in premature growth
      restricted lambs.
AB  - Fetal growth restriction (FGR) and prematurity are associated with risk of brain
      injury and long-term neurological deficits. FGR infants born preterm are commonly
      exposed to mechanical ventilation, but it is not known whether ventilation
      differentially induces brain pathology in FGR infants, compared to appropriate
      for gestational age (AGA) infants. We investigated markers of neuropathology in
      preterm FGR lambs, compared with AGA lambs, delivered by caesarean birth and
      ventilated under standard neonatal conditions for 24 hours. FGR was induced by
      single umbilical artery ligation in fetal sheep at 88d gestation (term, 150d). At
      125d gestation, FGR and AGA lambs were delivered, dried, intubated and commenced
      on non-injurious ventilation, with surfactant administration at 10 min. A group
      of unventilated FGR and AGA lambs at the same gestation were also examined. Over
      24 hours, circulating pH, pO2 and lactate levels were similar between groups.
      Ventilated FGR lambs had lower cerebral blood flow compared to AGA lambs
      (p=0.01). The brain of ventilated FGR lambs showed neuropathology compared to
      unventilated FGR, and unventilated and ventilated AGA lambs, with increased
      apoptosis (caspase-3), blood brain barrier dysfunction (albumin extravasation),
      activated microglia (Iba-1), and increased expression of cellular oxidative
      stress (4HNE). The neuropathologies seen in the ventilated FGR brain were most
      pronounced in the periventricular and subcortical white matter, but also evident
      in the subventricular zone, cortical grey matter and hippocampus. Ventilation of
      preterm FGR lambs increased brain injury compared to AGA preterm lambs and
      unventilated FGR lambs, mediated via increased vascular permeability,
      neuroinflammation and oxidative stress.

PMID- 30230934
TI  - Microbiota modulation by eating patterns, dietary and macronutrient composition;
      impact on food intake.
AB  - There is accumulating evidence that the gut microbiota and its composition
      dynamics play a crucial role in regulating the host physiological functions and
      behavior. Diet composition is the primary modulator of bacterial richness and
      abundance in the gastrointestinal (GI) tract. Macronutrient (fat, sugar and
      protein) and fiber contents are especially important in determining microbiota
      composition and its effect on health outcomes and behavior. In addition to food
      composition, time of intake and eating patterns have recently been shown to
      significantly affect gut bacterial make up. Diet-driven unfavorable microbiota
      composition or dysbiosis can lead to an increased production of pro-inflammatory
      byproducts such as lipopolysaccharide (LPS). Increased inflammatory potential is
      associated with alteration in gut permeability, resulting in elevated levels of
      LPS in the bloodstream, or metabolic endotoxemia. We have found that a chronic
      increase in circulating LPS is sufficient to induce hyperphagia in rodents.
      Chronic LPS treatment appears to specifically impair the gut-brain axis and
      vagally-mediated satiety signaling. The vagus nerve relays information on the
      quantity and quality of nutrients in the GI tract to the nucleus of solitary
      tract in the brainstem. There is evidence that microbiota dysbiosis is associated
      with remodeling of the vagal afferent pathway and that normalizing the microbiota
      composition in high fat diet (HFD) fed rats is sufficient to prevent vagal
      remodeling. Taken together, these data support a role for the microbiota in
      regulating gut-brain communication and eating behavior. Bacteria-originating
      inflammation may play a key role in impairment of diet-driven satiety and the
      development of hyperphagia.

PMID- 30230933
TI  - Hypoxia activates a neuropeptidergic pathway from the paraventricular nucleus of
      the hypothalamus to the nucleus tractus solitarii.
AB  - The paraventricular nucleus of the hypothalamus (PVN) contributes to both
      autonomic and neuroendocrine function. PVN lesion or inhibition blunts
      cardiorespiratory responses to peripheral chemoreflex activation, suggesting that
      the PVN is required for full expression of these effects. However, the role of
      efferent projections to cardiorespiratory nuclei and the
      neurotransmitters/neuromodulators that are involved is unclear. The PVN sends
      dense projections to the nucleus tractus solitarii (nTS), a region that displays
      neuronal activation following hypoxia. We hypothesized that acute hypoxia
      activates nTS-projecting PVN neurons. Using a combination of retrograde tracing
      and immunohistochemistry, we determined whether hypoxia activates PVN neurons
      that project to the nTS and examined the phenotype of these neurons. Conscious
      rats underwent 2 hr normoxia (21% O2, n=5) or hypoxia (10% O2, n=6). Hypoxia
      significantly increased Fos immunoreactivity in nTS-projecting neurons, primarily
      in the caudal PVN. The majority of activated nTS-projecting neurons contained
      corticotropin releasing hormone (CRH). In the nTS, fibers expressing the CRH
      receptor CRFR2 were co-localized with oxytocin fibers and were closely associated
      with hypoxia-activated nTS neurons. A separate group of animals that received
      microinjection of AAV2-hSyn-GFP into the PVN exhibited GFP-expressing fibers in
      the nTS; a proportion of these fibers displayed OT immunoreactivity. Thus, nTS
      CRFR2s appear to be located on the fibers of PVN OT neurons that project to the
      nTS. Taken together, our findings suggest that PVN CRH projections to the nTS may
      modulate nTS neuronal activation, possibly via OTergic mechanisms, and thus
      contribute to chemoreflex cardiorespiratory responses.

PMID- 30230937
TI  - Gene Therapy Briefs.

PMID- 30230936
TI  - DNA Vaccination in 2018: An Update.

PMID- 30230938
TI  - The RAC Retires After a Job Well Done.

PMID- 30230939
TI  - Endogenous Endophthalmitis Caused by Carbapenem-Resistant Hypervirulent
      Klebsiella Pneumoniae: A Case Report and Literature Review.
AB  - PURPOSE: To report a rare case of endogenous endophthalmitis caused by carbapenem
      resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). METHODS: A retrospective
      chart review was conducted. The isolates were characterized by
      hypermucoviscosity, resistance genes, virulence genes, and multilocus sequence
      typing. RESULTS: A 47-year-old diabetic woman acquired carbapenem-resistant K.
      pneumoniae (CRKP) nosocomial pneumonia. Metastatic endophthalmitis occurred in
      the right eye a week after the occurrence of CRKP bloodstream infection (BSI).
      Visual acuity decreased to light perception within 3 days. Although vitrectomy
      relieved ocular pain, endophthalmitis deteriorated due to uncontrollable BSI, and
      developed to corneal perforation. The strains isolated from bronchoalveolar
      lavage fluid, blood, and intraocular pus originated from the same clone. The
      pathogen was hypermucoviscous, belonged to sequence type 11, harbored resistance
      genes blaKPC-2, blaTEM, blaSHV, rmtB, and virulence genes rmpA2, iucABCD, iroBCD.
      CONCLUSIONS: Endogenous endophthalmitis caused by CR-hvKP has emerged, which is a
      treatment challenge for both ophthalmologists and physicians.

PMID- 30230940
TI  - Innate Immunity Biomarkers for Early Detection of Keratoconus.
AB  - PURPOSE: To compare toll-like receptors 2 (TLR2) and 4 (TLR4) expression in cells
      of corneal and conjunctival epithelium between unilateral KC patients and control
      subjects. METHODS: Prospective cross-sectional case-control study, including 50
      unilateral KC patients and 20 control subjects. TLR2 and TLR4 expression was
      measured with flow cytometry. RESULTS: Mean expression of TLR2 and TLR4, in
      corneal and conjunctival cells, was significantly higher in KC than in
      subclinical and control groups (all p < 0.0001). TLR2 expression in corneal
      epithelial cells can predict with the highest sensitivity and specificity the
      probability of KC existence compared to a control (area under the curve 0.995,
      95% CI: 0.987-1.000; p < 0.0001). Corneal TLR2 expression also has a predictive
      capacity to discriminate between subclinical KC and controls (area under the
      curve 0.989, 95% CI: 0.975-1.000; p < 0.0001). CONCLUSIONS: TLR2 and TLR4
      expression in corneal and conjunctival epithelial cells may constitute predictive
      biomarkers for the early detection of KC.

PMID- 30230941
TI  - Long-term renal function and hypertension in adult survivors of childhood
      sarcoma: Single center experience.
AB  - AIM: Little data is available on long-term renal impairment in survivors from
      childhood sarcoma. We investigated the prevalence of renal impairment and
      hypertension after very long-term follow-up in survivors who reached adulthood
      after treatment for childhood sarcoma. METHODS: A cross-sectional single center
      study was performed. Outcomes included estimating glomerular filtration rate
      (eGFR), albuminuria, glycosuria, serum phosphate and magnesium, tubular
      reabsorption phosphate (TRP), chronic kidney disease (CKD) according to the
      "Kidney Disease: Improving Global Outcomes" (KDIGO) guidelines and blood pressure
      (BP). RESULTS: Out of 87 > 5-year sarcoma survivors, 30 adults (10F/20M, median
      age at diagnosis 9 years, median age at investigation 26 years, median follow-up
      16 years, mean 19 years) were identified. Renal impairment was detected in four
      cases (13.3%); three of these fulfilled the criteria for CKD. Among the adult
      survivors, a subgroup of 15 cases (50%) had received ifosfamide without
      confounding factors such as a diagnosis of genito-urinary rhabdomyosarcoma or
      administration of other potentially nephrotoxic chemotherapy (platinum-based
      drugs or methotrexate); no renal dysfunction was detected in this subgroup. In
      the whole cohort of sarcoma survivors, hypertension was diagnosed in four cases
      (13.3%); BP was significantly correlated with body mass index [p .014].
      CONCLUSION: In our series of adult survivors treated for a diagnosis of sarcoma
      in their childhood, the prevalence of CKD was 10%. We found survivors treated
      with ifosfamide as the only nephrotoxic agent did not present glomerular or
      tubular toxicity at long term follow-up, but further studies including a larger
      number of cases are required to confirm it.

PMID- 30230942
TI  - Rural-Urban Residence and Stage at Breast Cancer Diagnosis Among Postmenopausal
      Women: The Women's Health Initiative.
AB  - BACKGROUND: Although social exposures have complex and dynamic relationships and
      interactions, the existing literature on the impact of rural-urban residence on
      stage at breast cancer diagnosis does not examine heterogeneity of effect. We
      examined the joint effect of social support, social relationship strain, and
      rural-urban residence on stage at breast cancer diagnosis. METHODS: Using data
      from the Women's Health Initiative (WHI) (n = 161,808), we describe the
      distribution of social, behavioral, and clinical factors by rural-urban residence
      among postmenopausal women with incident breast cancer (n = 7,120). We used rural
      urban commuting area (RUCA) codes to categorize baseline residential addresses as
      urban, large rural city/town, or small rural town, and the surveillance,
      epidemiology, and end results staging system to categorize breast cancer stage at
      diagnosis (dichotomized as early or late). We then used univariable and
      multivariable logistic regression to estimate odds ratios (ORs) and associated
      95% confidence intervals (95% CI) for the relationship between rural-urban
      residence and stage at breast cancer diagnosis. We included separate interaction
      terms between rural-urban residence and social strain and social support to test
      for statistical interaction. RESULTS: Of the social, behavioral, and clinical
      factors we examined, only younger age at WHI enrollment screening was
      significantly associated with late stage at breast cancer diagnosis (p = 0.003).
      Contrary to our hypothesis, rural-urban residence was not significantly
      associated with stage at breast cancer diagnosis among postmenopausal women
      ([adjusted OR, 95% CI] for urban compared with small town: 1.08 [0.76-1.53];
      large town compared with small town: 1.16 [0.74-1.84]; and urban compared with
      large town: 0.93 [0.68-1.26]).The associations did not vary by social support or
      social strain (p for interaction between RUCA and social strain and social
      support, respectively: 0.99 and 0.17). CONCLUSIONS: Future studies should examine
      other potential effect modifiers to identify novel factors predictive or
      protective for late stage at breast cancer diagnosis associated with rural-urban
      residence.

PMID- 30230943
TI  - Clinical Manifestations and Cerebrospinal Fluid Status in Ocular Syphilis.
AB  - PURPOSE: To review the clinical manifestations, cerebrospinal fluid findings and
      outcomes of patients diagnosed with ocular syphilis. METHODS: Retrospective case
      review of all patients treated with ocular syphilis at Groote Schuur Hospital in
      Cape Town, South Africa between January 2008 and January 2013. RESULTS: A total
      of 77 eyes of 49 patients were included. Panuveitis was the most common
      presenting sign (48.9%). A lumbar puncture was performed on 37 patients (75.5%)
      and 64.8% (24/37) of samples had positive treponemal testing (CSF-FTA) while
      24.3% (9/37) had positive non-treponemal testing (CSF-VDRL). Elevated CSF
      lymphocyte cell count was a strong predictor of neurosyphilis (p = 0.06 for CSF
      FTA positive samples and p = 0.03 for CSF-VDRL positive samples). CONCLUSION: The
      majority of patients (64.8%) who underwent lumbar puncture had cerebrospinal
      fluid findings suggestive of neurosyphilis. Elevated CSF lymphocyte cell count
      and total protein count are highly suggestive of neurosyphilis.

PMID- 30230944
TI  - IgY antibodies for the immunoprophylaxis and therapy of respiratory infections.
AB  - Emergence of drug resistance among the causative organisms for respiratory tract
      infections represents a critical challenge to the global health care community.
      Further, although vaccination can prevent disease, vaccine development is impeded
      by several factors. Therefore, novel approaches to treat and manage respiratory
      infections are urgently needed. Passive immunization represents a possible
      alternative to meet this need. Immunoglobulin Y antibodies (IgYs) from the yolk
      of chicken eggs have previously been used against bacterial and viral infections
      in human and animals. Their advantages include lack of reaction with mammalian Fc
      receptors, low production cost, and ease of extraction. Compared to mammalian
      IgGs, they have higher target specificity and greater binding avidity. They also
      possess remarkable pathogen-neutralizing activity in the respiratory tract and
      lungs. In this review, we provide an overview of avian IgYs and describe their
      potential therapeutic applications for the prevention and treatment of
      respiratory infections.

PMID- 30230945
TI  - MicroRNA-886-3P functions as a tumor suppressor in small cell lung cancer.
AB  - Small cell lung cancer (SCLC) is a highly aggressive disease and miRNAs may play
      an important role in modulating SCLC progression. We have previously screened 924
      miRNAs and found that miR-886-3P was negatively associated with SCLC survival. In
      the current study, we further investigated the role of miR-886-3P mimic in
      regulating SCLC cell phenotypic alteration in vitro and xenograft tumor formation
      in vivo. We found that transfection of miR-886-3P mimic significantly inhibited
      SCLC cell proliferation, migration, and colony formation, and induced mesenchymal
      epithelial transition (MET) by suppressing TGF-beta1 synthesis in vitro.
      Furthermore, intra-tumor injection of miR-886-3P mimic lead to necrosis and
      suppression of tumor invasion to the surrounding tissue in the subcutaneous
      xenograft tumor, and intra-vein injection of miR-886-3P mimic suppressed
      xenograft lung cancer growth in vivo. These findings suggested that miR-886-3P
      functions as a tumor suppressor in SCLC and thus, it might be a potential
      therapeutic molecule in the treatment of lung cancer.

PMID- 30230946
TI  - HPV vaccination acceptability among men who have sex with men in Urumqi, China.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is common among men who have sex
      with men (MSM), especially among Human Immunodeficiency Virus (HIV)-infected MSM.
      The prevalence of HPV among MSM, accounts for the higher incidence of HPV-related
      cancer observed in this population. It is well known that targeted HPV
      vaccination is an effective way to prevent HPV infection; an intervention which
      could be beneficial for a high-risk group such as MSM. The current study aimed to
      assess the attitudes towards and acceptability of the HPV vaccine among MSM in in
      Urumqi, China. METHODS: A total of 253 HIV-uninfected and 205 HIV-infected MSM
      (in Urumqi, China participated in the current cross-sectional study. Information
      on HPV-related knowledge, willingness to be vaccinated as well as demographic
      data were collected through a self-administered survey. A logistic regression
      model was applied to determine the predictors of HPV vaccine acceptability among
      the population. RESULTS: The survey results indicated that only 218 (47.6%) of
      MSM questioned were aware of the term HPV, nevertheless, once awareness was
      established the prevalence of acceptability of free HPV vaccine was recorded at
      96.7% of the total MSM sample. However, HIV-uninfected and HIV-infected MSM
      demonstrated significantly different attitudes in regard to their acceptability
      of free HPV vaccination (94.9% vs. 99.0%, p < 0.001) as well as their willingness
      to pay for the HPV vaccination (64.8% vs. 80.5%, p < 0.001), with the HIV
      infected group being significantly more receptive towards HPV immunization. A
      multivariate logistic regression analysis indicated that local residency,
      employment status, hepatitis B vaccination status, previous awareness of HPV and
      HIV status were independent predictors of the participants' willingness to pay
      for HPV vaccination. CONCLUSIONS: Participants in the current study demonstrated
      poor knowledge of HPV but the majority of MSM were willing to accept HPV vaccine
      after consultation; with HIV-infected MSM displaying higher acceptability towards
      a potential HPV vaccination than HIV-uninfected MSM. MSM who were previously
      aware of HPV were more likely to be willing to pay for HPV vaccine.

PMID- 30230948
TI  - Correction.

PMID- 30230947
TI  - Modeling the long-term persistence of neutralizing antibody in children and
      toddlers after vaccination with live attenuated Japanese encephalitis chimeric
      virus vaccine.
AB  - The live-attenuated Japanese encephalitis chimeric virus vaccine JE-CV
      (IMOJEV(r), Sanofi Pasteur) elicits a robust antibody response in children, which
      wanes over time. Clinical efficacy is based on a correlate of protection against
      JE infection defined as neutralizing antibody levels equal to or greater than the
      threshold of 10 (1/dil). Information on the duration of persistence of the JE
      antibody response above this threshold is needed. We constructed statistical
      models using 5-year persistence data from a randomised clinical trial
      (NCT00621764) in children (2-5 years old) primed with inactivated JE vaccine who
      received a booster dose of JE-CV, and in JE-naive toddlers (12-24 months) who
      received a JE-CV single dose primary vaccination. Models were constructed using a
      Bayesian Monte-Carlo Markov Chain approach and implemented with OpenBugs V3.2.1.
      Antibody persistence was predicted for up to 10 years following JE-CV
      vaccination. Findings from a piecewise model with 2 phases (children) and a
      classic linear model (toddlers) are presented. For children, predicted median
      antibody titers (77 [2.5th-97.5th percentile range 41-144] 1/dil) remained above
      the threshold for seroprotection over the 10 years following booster JE-CV
      vaccination; the predicted median duration of protection was 19.5 years. For
      toddlers, 10 years after JE-CV primary vaccination median antibody titers were
      predicted to wane to around the level required for seroprotection (10.8 [5.8
      20.1] 1/dil). A booster dose of JE-CV in children is predicted to provide long
      term protection against JE. Such data are useful to facilitate decisions on
      implementation of and recommendations for future vaccination strategies.

PMID- 30230949
TI  - Is immunisation education in midwifery degrees adequate?
AB  - Maternal and childhood vaccination decisions begin during pregnancy, and midwives
      are an important information resource. Their role is set to increase with the
      expansion of maternal immunisations into new jurisdictions, and new maternal
      vaccines in development. Meanwhile, other health providers are orienting parents
      towards vaccine acceptance, using strategies at odds with midwifery norms around
      information provision and maternal autonomy. To better understand and address the
      implications of these developments, we conducted a pilot study to ascertain how
      midwifery students in Australian universities are taught about immunisation,
      including dedicated time, assessment, who teaches it, and when. We also analysed
      teaching materials, looking for messaging regarding the importance of vaccination
      and whether midwives should be advocating for it. We found that education on
      immunisation comprises less than four hours of the degree, and encountered the
      norm of midwives informing about rather than recommending vaccination. The
      considerations we brought to our small project, and what it illuminated, suggest
      that midwifery university education is an important arena for developing future
      vaccine advocates. However, midwifery ideology and professional practice mean
      that such efforts will be challenging, and must commence from a position of
      respect for the values midwives hold.

PMID- 30230950
TI  - Burden, Prevalence, and Treatment of Uterine Fibroids: A Survey of U.S. Women.
AB  - BACKGROUND: Most women will experience uterine fibroids by the age of 50, yet few
      data exist describing the overall patient experience with fibroids. The objective
      of this population-based survey was to characterize symptom burden, patient
      awareness, and treatment decision-making for fibroids, including a comparison
      among women of varying backgrounds. MATERIALS AND METHODS: Women (>=18 years)
      were recruited via email from GfK KnowledgePanel(r), a representative panel of US
      households, or identified with opt-in consumer panels. The Uterine Fibroid
      Symptom and Health-Related Quality of Life (UFS-QOL) questionnaire and Aberdeen
      Menorrhagia Severity Scale (AMSS) were included. RESULTS: Eligible women were
      grouped into three cohorts: "at-risk" (symptoms suggestive of fibroids without
      clinical diagnosis, n = 300), "diagnosed" (n = 871), and fibroid-related
      "hysterectomy" (n = 272). Cohort and intracohort race/ethnicity and income
      analyses revealed differences in symptom burden, awareness/perception, and
      treatment history. Based on UFS-QOL scores, at-risk women reported significantly
      greater symptom severity and decreased health-related QOL versus diagnosed women;
      Hispanic women reported greater symptom severity versus white and black women. At
      risk women also reported heavy menstrual bleeding and significant impact on work
      productivity. Among diagnosed women, 71% used pharmacologic therapy for symptom
      relief, and 30% underwent surgical or procedural treatment. Initial discussions
      with healthcare providers significantly impacted treatment outcomes; the
      hysterectomy cohort was most likely to first discuss hysterectomy. CONCLUSIONS:
      Women with fibroids or symptoms suggestive of fibroids experience significant
      distress that reduces QOL, particularly racial minorities and women in lower
      income brackets. Survey results suggest that many women are likely undiagnosed,
      underscoring the need for improved awareness and education.

PMID- 30230952
TI  - Symptomatology and symptomatic treatment in multiple sclerosis: Results from a
      nationwide MS registry.
AB  - BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative
      disease. Over time, symptoms accumulate leading to increased disability of
      patients. OBJECTIVE: The objective of this article is to analyze the prevalence
      of symptoms and symptomatic treatment patterns in a nationwide MS registry.
      METHODS: Data sets from 35,755 patients were analyzed. RESULTS: More than two
      thirds of patients were women with a mean age of 46.1 (+/-12.8) years. Median
      Expanded Disability Status Score (EDSS) was 3.0. The most frequently reported
      symptoms were fatigue, spasticity, and voiding disorders. In patients with short
      disease duration, fatigue was reported most frequently. Symptomatic treatment was
      most common for spasticity and depression, whereas fatigue was treated only in a
      third of affected patients. Almost a fifth of patients with EDSS ? 3.5 and
      neuropsychological symptoms had retired from work. CONCLUSION: Whereas treatment
      for spasticity and depression is common in our cohort, sexual dysfunction,
      dysphagia, cognitive dysfunction, and fatigue are treated to a far lesser extent.
      The need for psychological support, physical, and occupational therapy has to be
      recognized as neuropsychological symptoms have a great impact on retirement at an
      early stage. Overall symptomatic treatment rates for the most common symptoms
      have increased over the last years ( p < 0.001).

PMID- 30230951
TI  - A novel role for PsbO1 in photosynthetic electron transport as suggested by its
      light-triggered selective nitration in Arabidopsis thaliana.
AB  - Exposure of Arabidopsis leaves to nitrogen dioxide (NO2) results in the selective
      nitration of specific proteins, such as PsbO1. The 9th tyrosine residue (9Tyr) of
      PsbO1 has been identified as the nitration site. This nitration is triggered by
      light and inhibited by photosynthetic electron transport inhibitors. During
      protein nitration, tyrosyl and NO2 radicals are formed concurrently and combine
      rapidly to form 3-nitrotyrosine. A selective oxidation mechanism for 9Tyr of
      PsbO1 is required. We postulated that, similar to 161Tyr of D1, 9Tyr of PsbO1 is
      selectively photo-oxidized by photosynthetic electron transport in response to
      illumination to a tyrosyl radical. In corroboration, after reappraising our
      oxygen evolution analysis, the nitration of PsbO1 proved responsible for
      decreased oxygen evolution from the thylakoid membranes. NO2 is reportedly taken
      into cells as nitrous acid, which dissociates to form NO2-. NO2- may be oxidized
      into NO2 by the oxygen-evolving complex. Light may synchronize this reaction with
      tyrosyl radical formation. These findings suggest a novel role for PsbO1 in
      photosynthetic electron transport.

PMID- 30230953
TI  - Vaccination herd effect experience in Latin America: a systematic literature
      review.
AB  - BACKGROUND: National pediatric vaccination programs have been introduced in Latin
      America (LatAm) to reduce the burden of diseases due to pathogens such as
      rotavirus, Haemophilus influenzae type b (Hib) and pneumococcus. Vaccination
      health benefits may extend to unvaccinated populations by reducing pathogen
      transmission. Understanding herd effect is important for implementation and
      assessment of vaccination programs. The objective was to conduct a systematic
      review of published epidemiological evidence of herd effect with Hib, rotavirus
      and pneumococcal conjugate vaccines (PCV) in LatAm. METHODS: Searches were
      conducted in PubMed, Virtual Health Library (VHL), SciELO and SCOPUS databases,
      for studies reporting data on herd effect from Hib, rotavirus and PCV vaccination
      in LatAm, without age restriction. Searches were limited to articles published in
      English, Spanish or Portuguese (1990-2016). After screening and full-text review,
      articles meeting the selection criteria were included to be critically appraised
      following criteria for observational and interventional studies. The presence of
      a herd effect was defined as a significant decrease in incidence of disease,
      hospitalization, or mortality. RESULTS: 3,465 unique articles were identified,
      and 23 were included (Hib vaccine n = 5, PCV n = 8, rotavirus vaccine n = 10).
      Most studies included children and/or adolescents (age range varied between
      studies). Studies in adults, including older adults (aged > 65 years), were
      limited. Few studies reported statistically significant reductions in disease
      incidence in age groups not targeted for vaccination. Hib-confirmed meningitis
      hospitalization decreased in children but herd effect could not be quantified.
      Some evidence of herd effect was identified for PCV and rotavirus vaccine in
      unvaccinated children. Evidence for herd effects due to PCV in adults was
      limited. CONCLUSION: After introduction of Hib, PCV and rotavirus vaccination in
      LatAm, reductions in morbidity/mortality have been reported in children not
      targeted for vaccination. However, due to methodological limitations (e.g. short
      post-vaccination periods and age range studied), there is currently insufficient
      evidence to quantify the herd effect in adult populations. More research and
      higher quality surveillance is needed to characterize herd effect of these
      vaccines in LatAm.

PMID- 30230954
TI  - PPP1R35 ensures centriole homeostasis by promoting centriole-to-centrosome
      conversion.
AB  - Centriole-to-centrosome conversion (CCC) safeguards centriole homeostasis by
      coupling centriole duplication with segregation, and is essential for
      stabilization of mature vertebrate centrioles naturally devoid of the geometric
      scaffold or the cartwheel. Here we identified PPP1R35, a putative regulator of
      the protein phosphatase PP1, as a novel centriolar protein required for CCC. We
      found that PPP1R35 is enriched at newborn daughter centrioles in S or G2 phase.
      In the absence of PPP1R35, centriole assembly initiates normally in S phase, but
      none of the nascent centrioles can form active centrosomes or recruit CEP295, an
      essential factor for CCC. Instead, all PPP1R35-null centrioles, although stable
      during their birth in interphase, become disintegrated after mitosis upon
      cartwheel removal. Surprisingly, we found that neither the centriolar
      localization nor the function of PPP1R35 in CCC requires the putative PP1
      interacting motif. PPP1R35 is thus acting upstream of CEP295 to induce CCC for
      proper centriole maintenance.

PMID- 30230956
TI  - Comprehensive characterization of monoclonal antibody by Fourier transform ion
      cyclotron resonance mass spectrometry.
AB  - The pharmaceutical industry's interest in monoclonal antibodies (mAbs) and their
      derivatives has spurred rapid growth in the commercial clinical pipeline of these
      effective therapeutics. The complex micro-heterogeneity of mAbs requires in-depth
      structural characterization for critical quality attribute assessment and quality
      assurance. Currently, mass spectrometry (MS)-based methods are the gold standard
      in mAb analysis, primarily with a bottom-up approach in which immunoglobulins G
      (IgGs) and their variants are digested into peptides to facilitate the analysis.
      Comprehensive characterization of IgGs and the micro-variants remains challenging
      at the proteoform level. Here, we used both top-down and middle-down MS for in
      depth characterization of a human IgG1 using ultra-high resolution Fourier
      transform MS. Our top-down MS analysis provided characteristic fingerprinting of
      the IgG1 proteoforms at unit mass resolution. Subsequently, the tandem MS
      analysis of intact IgG1 enabled the detailed sequence characterization of a
      representative IgG1 proteoform at the intact protein level. Moreover, we used the
      middle-down MS analysis to characterize the primary glycoforms and micro
      variants. Micro-variants such as low-abundance glycoforms, C-terminal glycine
      clipping, and C-terminal proline amidation were characterized with bond cleavages
      higher than 44% at the subunit level. By combining top-down and middle-down
      analysis, 76% of bond cleavage (509/666 amino acid bond cleaved) of IgG1 was
      achieved. Taken together, we demonstrated the combination of top-down and middle
      down MS as powerful tools in the comprehensive characterization of mAbs.

PMID- 30230955
TI  - Intracellular mechanism by which genotoxic stress activates yeast SAPK Mpk1.
AB  - Stress-activated MAP kinases (SAPKs) respond to a wide variety of stressors. In
      most cases, the pathways through which specific stress signals are transmitted to
      the SAPKs are not known. The Saccharomyces cerevisiae SAPK Mpk1 (Slt2) is a well
      characterized component of the cell-wall integrity (CWI) signaling pathway, which
      responds to physical and chemical challenges to the cell wall. However, Mpk1 is
      also activated in response to genotoxic stress through an unknown pathway. We
      show that, in contrast to cell-wall stress, the pathway for Mpk1 activation by
      genotoxic stress does not involve the stimulation of the MAP kinase kinases
      (MEKs) that function immediately upstream of Mpk1. Instead, DNA damage activates
      Mpk1 through induction of proteasomal degradation of Msg5, the dual-specificity
      protein phosphatase principally responsible for maintaining Mpk1 in a low
      activity state in the absence of stress. Blocking Msg5 degradation in response to
      genotoxic stress prevented Mpk1 activation. This work raises the possibility that
      other Mpk1-activating stressors act intracellularly at different points along the
      canonical Mpk1 activation pathway.

PMID- 30230957
TI  - Liver injury with drugs used for multiple sclerosis: A contemporary analysis of
      the FDA Adverse Event Reporting System.
AB  - BACKGROUND: Drug-induced liver injury (DILI) has been observed in patients with
      multiple sclerosis (MS), raising concerns on the liver safety of MS drugs.
      OBJECTIVE: To describe DILI events with MS drugs by analyzing the FDA Adverse
      Event Reporting System. METHODS: DILI reports were extracted and classified in
      overall liver injury (OLI), including asymptomatic elevation of liver enzymes,
      and severe liver injury (SLI). We performed disproportionality analysis by
      calculating adjusted reporting odds ratios (RORs) with 95% confidence interval
      (CI) and case-by-case evaluation for concomitant drugs with hepatotoxic
      potential. RESULTS: Fampridine showed statistically significant ROR for both OLI
      and SLI, whereas teriflunomide and fingolimod generated solid disproportionality
      (ROR > 2) only for OLI (ROR, 2.31; 95% CI, 2.12-2.52; and 2.53; 2.40-2.66,
      respectively). Among monoclonal antibodies, only alemtuzumab generated higher
      than-expected ROR for OLI (1.34; 1.09-1.65). We also detected the expected
      hepatotoxic potential of beta interferon and mitoxantrone. Concomitant reporting
      of hepatotoxic drugs ranged from 26% (dimethyl fumarate) to 90% (mitoxantrone).
      CONCLUSION: These real-world pharmacovigilance findings suggest that DILI might
      be a common feature of MS drugs and call for (1) formal population-based study to
      verify the risk of fampridine and (2) awareness by clinicians, who should assess
      the possible responsibility of MS drugs when they diagnose DILI.

PMID- 30230958
TI  - Estimates of parameters for formaldehyde emission model from plywood panel under
      various temperature and relative humidity conditions.
AB  - The initial emittable concentration, Cm,0, the material phase diffusion
      coefficient, Dm, and the air/material partition coefficient, K, are the key
      parameters used to predict the formaldehyde emissions from indoor building
      materials. This work presents formaldehyde emission experiments of plywood panels
      in a climatic chamber under various environmental conditions, which provides
      information on how relative humidity, temperature, and loading degree affect the
      formaldehyde emission. The experimental results showed that formaldehyde
      concentration in the climatic chamber increased rapidly during the initial 3 h,
      and then reached equilibrium after 7 h. The equilibrium concentration of
      formaldehyde in the closed chamber was increased by 1.1-1.3 times with the
      relative humidity increased by 20%, and 1.3-2.5 times with the temperature
      increased by 5  degrees C, respectively. In agreement with the experimental
      treatment, a new method of estimating parameters was carried out in a theoretical
      model from formaldehyde emission, opening the way to a factorial analysis of the
      relevant parameters for relative humidity and temperature. The theoretical model
      with estimated parameters was further validated by experiments with different
      environmental conditions, which should help to quickly determine the parameters
      needed to predict formaldehyde emissions.

PMID- 30230959
TI  - Long-term survival of pancreatic cancer patients treated with multimodal therapy
      combined with WT1-targeted dendritic cell vaccines.
AB  - BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDA) remains one of the most
      aggressive tumors with a dismally poor prognosis. Although surgical resection
      remains the only potentially curative treatment, most PDAs are not surgically
      resectable at diagnosis. Therefore, multimodal therapy is urgently needed to
      improve the long-term survival of PDA patients. METHODS: Six eligible PDA
      patients underwent multimodal therapy comprising dendritic cells (DCs) pulsed
      with Wilms' tumor 1 (WT1) peptide (DC/WT1-I) restricted by the human leukocyte
      antigen (HLA) class I (A*24:02 or A*02:06) allele, chemotherapy, radiation,
      and/or surgery. Patient laboratory data, DC/WT1-I-specific delayed-type
      hypersensitivity (DTH) reactions, and WT1-specific immune responses were analyzed
      to assess the prognostic markers of multimodal therapy. RESULTS: Compared to 2
      treatment type combinations, multimodal therapy involving 3 to 4 treatment types
      was significantly associated with longer overall survival (p = 0.0177). Moreover,
      after 7 DC/WT1-I vaccinations, the progression-free survival (PFS) of PDA
      patients with a neutrophil to lymphocyte ratio (NLR) or C-reactive protein (CRP)
      level less than the median was superior to that of PDA patients with values above
      the median (p = 0.0246). PDA patients with an overall survival (OS)>1000 days had
      significantly more lymphocytes after one DC/WT1-I vaccination course than did
      those with an OS<1000 days. CONCLUSION: Multimodal therapy involving the DC/WT1-I
      vaccination may benefit patients with advanced PDA. However, comparing the
      limited number of PDA patients in terms of survival is difficult because the
      patients were at different disease stages and received different treatments.
      Further studies are needed to evaluate the clinical benefits of this multimodal
      therapy.

PMID- 30230960
TI  - Novel Clinical Toxicology and Pharmacology of Organophosphorus Insecticide Self
      Poisoning.
AB  - Organophosphorus insecticide self-poisoning is a major global health problem,
      killing over 100,000 people annually. It is a complex multi-organ condition,
      involving the inhibition of cholinesterases, and perhaps other enzymes, and the
      effects of large doses of ingested solvents. Variability between organophosphorus
      insecticides-in lipophilicity, speed of activation, speed and potency of
      acetylcholinesterase inhibition, and in the chemical groups attached to the
      phosphorus-results in variable speed of poisoning onset, severity, clinical
      toxidrome, and case fatality. Current treatment is modestly effective, aiming
      only to reactivate acetylcholinesterase and counter the effects of excess
      acetylcholine at muscarinic receptors. Rapid titration of atropine during
      resuscitation is lifesaving and can be performed in the absence of oxygen. The
      role of oximes in therapy remains unclear. Novel antidotes have been tested in
      small trials, but the great variability in poisoning makes interpretation of such
      trials difficult. More effort is required to test treatments in adequately
      powered studies. Expected final online publication date for the Annual Review of
      Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30230961
TI  - Payment and Delivery-System Reform - The Next Phase.

PMID- 30230962
TI  - Treatment of active rheumatoid arthritis: comparison of patients younger vs older
      than 75 years (CORPUS cohort).
AB  - OBJECTIVES: Little information is available on the characteristics of elderly
      patients starting TNFalpha antagonist treatment for rheumatoid arthritis (RA).
      The objective of this work was to compare prescription patterns in RA patients
      younger vs. older than 75 years. METHODS: Biologic-naive patients with active RA
      (DAS28 > 3.2) despite first-line therapy were included between 2007 and 2009 in
      the prospective, multicentre, longitudinal, observational, population-based
      CORPUS-RA cohort. TNFalpha antagonist users were defined as having received at
      least one TNFalpha antagonist during the first study year. The groups < 75 years
      and >= 75 years were compared regarding comorbidities, inflammation (CRP and
      ESR), disease activity (DAS28), disability (HAQ-DI), number of physician visits,
      and treatment. To verify the impact of the cut off, we also compared patients
      aged 70 years or more to patients younger than 70 years. RESULTS: Of 543 RA
      patients, 382 had complete one-year follow-up data, including 114 TNFalpha
      antagonist users, 3 (6%) among the 49 patients aged 75 years or over and 111
      (32%) of the 333 patients younger than 75 years (p < 0.01). Disease activity in
      the two age groups was similar at inclusion and after one year. Comorbidities and
      a history of auto-immunity were more common in the older group. Compared to their
      younger counterparts, the older patients received glucocorticoids more often (p =
      0.003) and synthetic disease-modifying anti-rheumatic drugs less often (p =
      0.01). CONCLUSION: TNFalpha antagonists are used less often and glucocorticoids
      more often in elderly patients with active RA compared to their younger
      counterparts. The fact that this study was performed in 2007-9 is a limitation in
      terms of relevance to today's patients and further studies should be conducted in
      new cohorts of active RA.

PMID- 30230964
TI  - Active Surveillance as First-Line Management of Papillary Microcarcinoma.
AB  - Papillary thyroid microcarcinoma (PMC) is defined as papillary thyroid carcinoma
      <=10 mm. Active surveillance of PMC without high-risk features, such as clinical
      node metastasis, distant metastasis, and clinical evidence of significant
      extrathyroid extension, was initiated in two Japanese hospitals in the mid-1990s.
      This strategy was incorporated into guidelines in Japan in 2010 and in the United
      States in 2015. In studies conducted by the two hospitals, most PMCs grew very
      slowly or did not grow, and none of the patients during active surveillance
      showed distant metastasis or died of thyroid carcinoma. Furthermore, none of the
      patients who underwent surgery after progression signs were detected showed
      significant recurrence. Therefore, we conclude that active surveillance should be
      the first line in management of low-risk PMC, because it is safer and less costly
      than immediate surgery. Active surveillance helps in avoiding adverse events of
      surgery and is an economical strategy. Expected final online publication date for
      the Annual Review of Medicine Volume 70 is January 27, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30230965
TI  - Being PrEPared - Preexposure Prophylaxis and HIV Disparities.

PMID- 30230966
TI  - Systematic development of temperature shift strategies for Chinese hamster ovary
      cells based on short duration cultures and kinetic modeling.
AB  - Temperature shift (TS) to a hypothermic condition has been widely used during
      protein production processes that use Chinese hamster ovary (CHO) cells. The
      effect of temperature on cell growth, metabolites, protein titer and quality
      depends on cell line, product, and other bioreactor conditions. Due to the large
      numbers of experiments, which typically last 2-3 weeks each, limited systematic
      TS studies have been reported with multiple shift temperatures and steps at
      different times. Here, we systematically studied the effect of temperature on
      cell culture performance for the production of two monoclonal antibodies by
      industrial GS and DG44 CHO cell lines. Three 2-8 day short-duration methods were
      developed and validated for researching the effect of many different temperatures
      on CHO cell culture and quality attributes. We found that minor temperature
      differences (1-1.5  degrees C) affected cell culture performance. The kinetic
      parameters extracted from the short duration data were subsequently used to
      compute and predict cell culture performance in extended duration of 10-14 days
      with multiple TS conditions for both CHO cell lines. These short-duration culture
      methods with kinetic modeling tools may be used for effective TS optimization to
      achieve the best profiles for cell growth, metabolites, titer and quality
      attributes. Although only three short-duration methods were developed with two
      CHO cell lines, similar short-duration methods with kinetic modeling may be
      applied for different hosts, including both microbial and other mammalian cells.

PMID- 30230967
TI  - Innate Immune Signaling in Nonalcoholic Fatty Liver Disease and Cardiovascular
      Diseases.
AB  - The physiological significance of innate immune signaling lies primarily in its
      role in host defense against invading pathogens. It is becoming increasingly
      clear that innate immune signaling also modulates the development of metabolic
      diseases, especially nonalcoholic fatty liver disease and cardiovascular
      diseases, which are characterized by chronic, low-grade inflammation due to a
      disarrangement of innate immune signaling. Notably, recent studies indicate that
      in addition to regulating canonical innate immune-mediated inflammatory responses
      (or immune-dependent signaling-induced responses), molecules of the innate immune
      system regulate pathophysiological responses in multiple organs during metabolic
      disturbances (termed immune-independent signaling-induced responses), including
      the disruption of metabolic homeostasis, tissue repair, and cell survival. In
      addition, emerging evidence from the study of immunometabolism indicates that the
      systemic metabolic status may have profound effects on cellular immune function
      and phenotypes through the alteration of cell-intrinsic metabolism. We summarize
      how the innate immune system interacts with metabolic disturbances to trigger
      immune-dependent and immune-independent pathogenesis in the context of
      nonalcoholic fatty liver disease, as representative of metabolic diseases, and
      cardiovascular diseases. Expected final online publication date for the Annual
      Review of Pathology: Mechanisms of Disease Volume 14 is January 24, 2019. Please
      see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30230963
TI  - Body Temperature, Heart Rate, and Short-Term Outcome of Cooled Infants.
AB  - Therapeutic hypothermia following neonatal encephalopathy is neuroprotective.
      However, approximately one in two cooled infants still die or develop permanent
      neurological impairments. Further understanding of variables associated with the
      effectiveness of cooling is important to improve the therapeutic regimen. To
      identify clinical factors associated with short-term outcomes of cooled infants,
      clinical data of 509 cooled infants registered to the Baby Cooling Registry of
      Japan between 2012 and 2014 were evaluated. Independent variables of death during
      the initial hospitalization and survival discharge from the cooling hospital at
      <=28 days of life were assessed. Death was associated with higher Thompson scores
      at admission (p < 0.001); higher heart rates after 3-72 hours of cooling (p <
      0.001); and higher body temperature after 24 hours of cooling (p = 0.002).
      Survival discharge was associated with higher 10 minutes Apgar scores (p <
      0.001); higher blood pH and base excess (both p < 0.001); lower Thompson scores
      (at admission and after 24 hours of cooling; both p < 0.001); lower heart rates
      at initiating cooling (p = 0.003) and after 24 hours of cooling (p < 0.001) and
      lower average values after 3-72 hours of cooling (p < 0.001); higher body
      temperature at admission (p < 0.001); and lower body temperature after 24 hours
      and lower mean values after 3-72 hours of cooling (both p < 0.001). Survival
      discharge was best explained by higher blood pH (p < 0.05), higher body
      temperature at admission (p < 0.01), and lower body temperature and heart rate
      after 24 hours of cooling (p < 0.01 and <0.001, respectively). Lower heart rate,
      higher body temperature at admission, and lower body temperature during cooling
      were associated with favorable short-term outcomes.

PMID- 30230968
TI  - Characterization of the incipient smoke point for steam-/air-assisted and
      nonassisted flares.
AB  - Flares are important safety devices for pressure relief; at the same time, flares
      are a significant point source for soot and highly reactive volatile organic
      compounds (HRVOCs). Currently, simple guidelines for flare operations to maintain
      high combustion efficiency (CE) remain elusive. This paper fills the gap by
      investigating the characteristics of the incipient smoke point (ISP), which is
      widely recognized as the condition for good combustion. This study characterizes
      the ISP in terms of 100-% combustion inefficiency (CE), percent opacity,
      absorbance, air assist, steam assist, air equivalence ratio, steam equivalence
      ratio, exit velocity, vent gas net heating value, and combustion zone net heating
      value. Flame lengths were calculated for buoyant and momentum-dominated plumes
      under calm and windy conditions at stable and neutral atmosphere. Opacity was
      calculated using the Beer-Lambert law based on soot concentration, flame
      diameter, and mass-specific extinction cross section of soot. The calculated
      opacity and absorbance were found to be lognormally distributed. Linear relations
      were established for soot yield versus absorptivity with R2 > 0.99 and power-law
      relations for opacity versus soot emission rate with R2 >= 0.97 for steam
      assisted, air-assisted, and nonassisted flares. The characterized steam/air
      assists, combustion zone/vent gas heating values, exit velocity, steam, and air
      equivalence ratios for the incipient smoke point will serve as a useful guideline
      for efficient flare operations. Implications: A Recent EPA rule requires an
      evaluation of visible emissions in terms of opacity in compliance with the
      standards. In this paper, visible emissions such as soot particles are
      characterized in terms of opacity at ISP. Since ISP is widely recognized as most
      efficient flare operation for high combustion efficiency (CE)/destruction
      efficiency (DE) with initial soot particles formed in the flame, this
      characterization provides a useful guideline for flare operators in the refinery,
      oil and gas, and chemical industries to sustain smokeless and high combustion
      efficiency flaring in compliance with recent EPA regulations, in addition to
      protecting the environment.

PMID- 30230969
TI  - A comparative analysis of Lophodermium fissuratum, sp. nov., found in haploxylon
      pine needles in the Pacific Northwest, and other Lophodermium endophytes.
AB  - Lophodermium is a large fungal genus consisting of over 100 named species, with
      ca. 38 of these commonly found as endophytes of pine needles. In this study, we
      use both morphological and sequencing data to describe a new Lophodermium species
      associated with haploxylon pines from the Pacific Northwest. This new species
      resembled the morphology of L. nitens, another commonly occurring species from
      the same geographic regions and host species. They both present dark subcuticular
      ascocarps without lips. However, the upper walls of their ascocarps are
      different, as the new species forms an inward V-shaped folding, not present in L.
      nitens. Phylogenies using nuc rDNA internal transcribed spacer barcodes (ITS1
      5.8S-ITS2 = ITS), partial D1-D2 domains of nuc rDNA 28S, and partial sequences of
      the nuc actin gene confirmed that this species represents a unique lineage not
      closely related to L. nitens. We discuss the current state of the phylogeny in
      light of all currently available sequences from pine-associated Lophodermium
      species.

PMID- 30230970
TI  - A single-session positive cognitive intervention on first-year students' mental
      health: Short-term effectiveness and the mediating role of strengths knowledge.
AB  - OBJECTIVE: To better understand the effectiveness of a single-session positive
      cognitive intervention and uncover the possible mechanisms. PARTICIPANTS:
      Participants were 79 first-year students (aged 17-21) who volunteered for the
      intervention during the 2016 fall semester. METHODS: Participants were randomly
      assigned into the intervention group and the control group. All participants
      completed pretest, post-test, 1 week, and 3-month follow-up tests. Thriving,
      negative emotional states, strengths knowledge were assessed. RESULTS: Results
      showed significant increases of thriving in the intervention group at post-test
      and after 1 week, and significant decreases of negative emotions at the post-test
      and after 1 week and 3 months. Strengths knowledge fully mediated the
      intervention effect on thriving at post-test. CONCLUSIONS: The single-session
      positive cognitive intervention could be a responsive and effective approach to
      promote first-year students mental health. More attention should be paid to
      mechanisms of the single-session positive cognitive intervention so as to
      optimize the effects of the single-session positive cognitive intervention.

PMID- 30230971
TI  - Analysis of autoantibody profiles in two asbestiform fiber exposure cohorts.
AB  - An increased risk for Systemic Autoimmune Diseases (SAID) was reported in the
      population of Libby, Montana, where extensive exposure to asbestiform amphiboles
      occurred through mining and use of asbestiform fiber-laden vermiculite. High
      frequencies of antinuclear autoantibodies (ANA) were detected in individuals and
      mice exposed to Libby Asbestiform Amphiboles (LAA). Among the 6603 individuals
      who have undergone health screening at the Center for Asbestos Related Diseases
      (CARD, Libby MT), the frequencies of rheumatoid arthritis, systemic lupus
      erythematosus, sarcoidosis, and systemic sclerosis are significantly higher than
      expected prevalence in the United States. While these data support the hypothesis
      that LAA can trigger autoimmune responses, evidence suggests that chrysotile
      asbestos does not. Serological testing was therefore performed in subjects
      exposed to LAA or predominantly chrysotile (New York steamfitters) using
      multiplexed array technologies. Analyses were performed in order to determine a)
      autoantibody profiles in each cohort, and b) whether the two populations could be
      distinguished through predictive modeling. Analysis using perMANOVA testing
      confirmed a significant difference between autoantibody profiles suggesting
      differential pathways leading to autoantibody formation. ANA were more frequent
      in the LAA cohort. Specific autoantibodies more highly expressed with LAA
      exposure were to histone, ribosomal P protein, Sm/Ribonucleoproteins, and Jo-1
      (histidyl tRNA synthetase). Myositis autoantibodies more highly expressed in the
      LAA cohort were Jo-1, PM100, NXP2, and Mi2a. Predictive modeling demonstrated
      that anti-histone antibodies were most predictive for LAA exposure, and anti-Sm
      was predictive for the steamfitters' exposure. This emphasizes the need to
      consider fiber types when evaluating risk of SAID with asbestos exposure.

PMID- 30230972
TI  - Application of the adverse outcome pathway (AOP) approach to inform mode of
      action (MOA): A case study with inorganic arsenic.
AB  - The aim of this study was to establish a process for deriving a chemical-specific
      mode of action (MOA) from chemical-agnostic adverse outcome pathway (AOPs), using
      inorganic arsenic (iAs) as a case study. The AOP developed for this case study
      are related to disruption of cellular signaling by chemicals that strongly bind
      to vicinal dithiols in cellular proteins, leading to disruption of inflammatory
      and oxidative stress signaling along with inhibition of the DNA damage responses.
      The proposed MOA for iAs incorporates this AOP, overlaid on a background of
      increasing oxidative stress and/or co-exposure to mutagenic chemicals or
      radiation. The most challenging aspect of developing a MOA from AOP is the
      incorporation of metabolism and dose-response, neither of which may be considered
      in the development of an AOP. The cellular responses to relatively low
      concentrations (below 100 parts per billion) of iAs in drinking water appear to
      be secondary to binding of trivalent arsenite and its trivalent metabolite,
      monomethyl arsenous acid to key cellular vicinal dithiols in target tissues,
      resulting in a co-carcinogenic MOA. The proposed AOP may also be applied to non
      cancer endpoints, enabling an integrated approach to conducting a risk assessment
      for iAs.

PMID- 30230973
TI  - Tip60 complex promotes expression of a differentiation factor to regulate
      germline differentiation in female Drosophila.
AB  - Germline stem cells (GSCs) self-renew and differentiate to sustain a continuous
      production of gametes. In the female Drosophila germ line, two differentiation
      factors, bag of marbles ( bam) and benign gonial cell neoplasm ( bgcn), work in
      concert in the stem cell daughter to promote the generation of eggs. In GSCs, bam
      transcription is repressed by signaling from the niche and is activated in stem
      cell daughters. In contrast, bgcn is transcribed in both the GSCs and stem cell
      daughters, but little is known about how bgcn is transcriptionally modulated.
      Here we find that the conserved protein Nipped-A acts through the Tat interactive
      protein 60-kDa (Tip60) histone acetyl transferase complex in the germ line to
      promote GSC daughter differentiation. We find that Nipped-A is required for
      efficient exit from the gap phase 2 (G2) of cell cycle of the GSC daughter and
      for expression of a differentiation factor, bgcn. Loss of Nipped-A results in
      accumulation of GSC daughters . Forced expression of bgcn in Nipped-A germline
      depleted ovaries rescues this differentiation defect. Together, our results
      indicate that Tip60 complex coordinates cell cycle progression and expression of
      bgcn to help drive GSC daughters toward a differentiation program.

PMID- 30230974
TI  - Occupational Coccidioidomycosis in a heavy equipment operator.
AB  - This paper describes a case of Coccidioidomycosis pneumonia in an individual who
      worked in the McKittrick Oil Field, Kern County, California, for fifteen days
      during an approximate one-month period in 2016. Coccidioidomycosis is caused by
      inhaling spores of Coccidioides immitis, a soil fungus endemic in regions of
      California, most notably the San Joaquin Valley. In California, Kern County has
      the highest incidence rate of Coccidioidomycosis, and the McKittrick Oil Field
      lies within the most highly endemic part of Kern County. The affected individual,
      who resided in a nonendemic state, traveled to Kern County to operate heavy
      equipment and also perform some laborer tasks. He experienced substantial
      exposure to soil dust without wearing adequate respiratory protection.
      Consideration of the relative amounts of soil dust exposure due to the
      individual's oil field work versus ambient air permits a conclusion that his
      infection was work-related. In addition to respiratory protection, some measures
      needed to reduce soil dust exposure during construction work in areas endemic for
      C. immitis are discussed.

PMID- 30230975
TI  - Barriers to college success among students that experienced adverse childhood
      events.
AB  - OBJECTIVE: This study examines the relationship between adverse childhood
      experiences (ACEs) and academic barriers to college success. PARTICIPANTS:
      College students (n = 525) were surveyed about exposure to ACEs and academic
      barriers on a large university campus in the Southeast. METHODS: Multivariate
      regression was used to model the academic barriers among college students for
      students with different levels of ACEs exposure controlling for depression,
      health and family barriers, and sociodemographic characteristics. RESULTS:
      Students with ACEs reported more family difficulties and health problems compared
      with those without ACEs. Depressive symptomology, poorer health ratings, and
      other health and family issues significantly predicted higher counts of academic
      barriers. CONCLUSIONS: Students with ACEs face greater difficulty with relation
      to health and family barriers which in turn impacts academic barriers.

PMID- 30230976
TI  - Efficacy of four cleaning solutions for the decontamination of selected cytotoxic
      drugs on the different surfaces of an automated compounding system.
AB  - The automated aseptic preparation of ready-to-administer antineoplastic drug
      solutions with robotic systems reduces the risk of occupational exposure.
      However, the surfaces in the preparation area of the robot are to be cleaned by
      wiping with an appropriate cleaning solution. The aim of the study was to
      evaluate the cleaning efficacy of four cleaning solutions on four surface
      materials installed in the APOTECAchemo robot. Predefined amounts of cisplatin
      (Cis), 5-fluorouracil (5-FU) and cyclophosphamide (CP) were intentionally spread
      on test plates made of stainless steel, aluminium, polyoxymethylene and
      polycarbonate just as installed in the robotic system APOTECAchemo. After drying,
      the plates were cleaned with 0.2% ethanolic NaOH, 0.23% isopropanolic sodium
      dodecylsulfate (SDS-2P), 0.5% sodium hypochlorite (NaOCl), and 0.1% benzalkonium
      chloride (BZK) solutions following a standardized wiping protocol. Residual
      contamination was recovered with wipe tests, Pt was quantified by voltammetry,
      and 5-FU and CP was quantified by gas chromatography-tandem mass spectrometry (GC
      MSMS). The mean residual contamination after cleaning and the cleaning efficacy
      (CE) rates were calculated and aggregated on different levels. The CE rates
      varied between 81.5% and 100% and lay in the majority of cases above 90%. The
      lowest CE rates were registered for Pt contamination. Especially on aluminium
      surfaces the residual contamination was high. The overall CE rates of the three
      different drugs and four different surface types amounted to 98.3% for NaOCl,
      97.9% for SDS-2P, 96.9% for ethanolic NaOH, and 96.5% for BZK. The tested
      cleaning solutions proved to be higher than 90% in most cases, but none of them
      was able to eliminate 100% of the intentional surface contamination of three
      antineoplastic drugs on the test plates. The cleaning efficacy varied according
      to the different surface types and antineoplastic drug. Results could be used in
      the daily clinical practice to develop and implement effective cleaning
      procedures.

PMID- 30230977
TI  - Effect modification of ambient particle mortality by radon: a time series
      analysis in 108 U.S. cities.

PMID- 30230978
TI  - The combined effect of granulocyte-colony stimulating factor (G-CSF) treatment
      and exercise in rats with spinal cord injury.
AB  - OBJECTIVE: To identify that the combined G-CSF and treadmill exercise is more
      effective in functional recovery after spinal cord injury (SCI). DESIGN: Rats
      were divided into 4 groups: a SCI group treated with G-CSF (G-CSF group, n = 6),
      a SCI group treated with treadmill exercise plus G-CSF (G-CSF/exercise group, n =
      6), a SCI group with treadmill exercise (exercise group, n = 6), and a SCI group
      without treatments (control group, n = 6). We performed laminectomy at the T8-10
      spinal levels with compression injury of the spinal cord in all rats. G-CSF (20
      MUg/ml) was administered intraperitoneally for 5 consecutive days after SCI in G
      CSF and G-CSF/exercise groups. From one week after surgery, animals in G
      CSF/exercise and exercise groups received 30 min of exercise 5 days per week for
      4 weeks. Functional recoveries were assessed using the Basso, Beattie, and
      Bresnahan (BBB) scale and the inclined plane test. Five weeks after SCI,
      hematoxylin and eosin staining for cavity size and immunohistochemistry for glial
      scar formation and neuro-regeneration factor expression were conducted. SETTING:
      Inha University School of medicine, Incheon, Korea Results: Rats in G
      CSF/exercise group showed the most effective functional recovery in the BBB scale
      and the inclined plane test, and spinal cord cavity size by injury were the
      smallest, and immunohistochemistry revealed expression of higher BDNF (brain
      derived neurotrophic factor) and VEGF (vascular endothelial growth factor) and
      lower GFAP (glial fibrillary acidic protein) than others. CONCLUSION: Combined
      treatment provided more effective neuroplasty and functional recovery than
      individual treatments.

PMID- 30230979
TI  - Ginger and 6-shogaol protect intestinal tight junction and enteric dopaminergic
      neurons against 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine in mice.
AB  - OBJECTIVE: Ginger and its compound, 6-shogaol, have been known for improving
      gastrointestinal (GI) function and reducing inflammatory responses in GI tract.
      Recently, the treatment of GI dysfunction has been recognized as an important
      part of the management of neurodegenerative diseases, especially for Parkinson's
      disease (PD). In this study, we investigated whether ginger and 6-shogaol
      attenuate disruptions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) on the intestinal barrier and the enteric dopaminergic neurons. METHODS:
      C57BL/6J mice received MPTP (30 mg/kg) for 5 days to induce GI alterations.
      Ginger (30, 100, 300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage
      feeding for 15 days including the period of MPTP injection. RESULTS: Ginger and 6
      shogaol protected intestinal tight junction proteins disrupted by MPTP in mouse
      colon. In addition, ginger and 6-shogaol suppressed the increase of inducible
      nitric oxide synthase, cyclooxygenase-2, TNF-alpha and IL-1beta activated by
      macrophage. Moreover, ginger and 6-shogaol suppressed the MPTP-induced enteric
      dopaminergic neuronal damage via increasing the cell survival signaling pathway.
      CONCLUSION: These results indicate that ginger and 6-shogaol restore the
      disruption of intestinal integrity and enteric dopaminergic neurons in an MPTP
      injected mouse PD model by inhibiting the processes of inflammation and
      apoptosis, suggesting that they may attenuate the GI dysfunction in PD patients.

PMID- 30230980
TI  - Cardiorespiratory Responses to Downhill Versus Uphill Running in Endurance
      Athletes.
AB  - PURPOSE: Mountain running races are becoming increasingly popular, although our
      understanding of the particular physiology associated with downhill running (DR)
      in trained athletes remains scarce. This study explored the cardiorespiratory
      responses to high-slope constant velocity uphill running (UR) and DR. METHOD:
      Eight endurance athletes performed a maximal incremental test and 2 15-min
      running bouts (UR, +15%, or DR, -15%) at the same running velocity (8.5 +/- 0.4
      km.h-1). Oxygen uptake ([Formula: see text]O2), heart rate (HR), and ventilation
      rates ([Formula: see text]E) were continuously recorded, and blood lactate (bLa)
      was measured before and after each trial. RESULTS: Downhill running induced a
      more superficial [Formula: see text]E pattern featuring reduced tidal volume (p <
      .05, ES = 6.05) but similar respiratory frequency (p > .05, ES = 0.68) despite
      lower [Formula: see text]E (p < .05, ES = 5.46), [Formula: see text]O2 (p < .05,
      ES = 12.68), HR (p < .05, ES = 6.42), and bLa (p < .05, ES = 1.70). A negative
      slow component was observed during DR for [Formula: see text]O2 (p < .05, ES =
      1.72) and HR (p < .05, ES = 0.80). CONCLUSIONS: These results emphasize the
      cardiorespiratory responses to DR and highlight the need for cautious
      interpretation of [Formula: see text]O2, HR, and [Formula: see text]E patterns as
      markers of exercise intensity for training load prescription and management.

PMID- 30230981
TI  - Metformin Inhibits Chemokine Expression Through the AMPK/NF-kappaB Signaling
      Pathway.
AB  - Inflammation is mediated by cytokines and chemokines, which are considered
      targets of inflammatory diseases. Mounting evidence has demonstrated the anti
      inflammatory benefits of metformin. However, the underlying mechanisms are not
      completely understood. In this study, we aim to elucidate the regulatory effects
      of metformin on chemokine expression and the possible mechanisms using RAW264.7
      cells, a mouse macrophage cell line, as a model. First, we treated the cells with
      lipopolysaccharide (LPS), and found that the expression of CXCL10 and CXCL11 was
      markedly induced in a dose- and time-dependent fashion concurrent with the
      inhibition of AMPK activity. Then, we treated the cells with metformin, and
      analyzed the expression of CCL2, CXCL10, and CXCL11 by quantitative real-time
      polymerase chain reaction (PCR). We observed that metformin prevented the
      stimulating effect of LPS on these chemokines as well as IL-1 and IL-6. Second,
      the inhibitory effects of metformin on LPS-induced chemokine expression were
      diminished by Compound C, a chemical inhibitor of AMPK. Finally, we investigated
      whether the NF-kappaB signaling pathway is regulated by metformin in this
      setting. Our results showed that metformin inhibited the phosphorylation of I
      kappaBalpha and p65 while it activated AMPK. Therefore, the results suggest that
      metformin inhibits LPS-induced chemokine expression through the AMPK and NF
      kappaB signaling pathways.

PMID- 30230982
TI  - An Evidence-Based Meta-Analysis on the Roles of Functional Interleukin-6
      Polymorphisms in Coronary Artery Disease.
AB  - Recently, the relationship between functional interleukin-6 (IL-6) polymorphisms
      and coronary artery disease (CAD) was extensively studied, with controversial
      findings. Therefore, we conducted this meta-analysis to better elucidate the
      relationship between these polymorphisms and the risk of CAD. A total of 57 case
      control studies were finally included. The overall analyses showed that IL-6 
      174G>C and -572G>C polymorphisms were significantly associated with the risk of
      CAD, the C allele of -174G>C (G versus C, odds ratio [OR] = 0.82, confidence
      interval [95% CI] = 0.75-0.89) and -572G>C polymorphisms (G versus C, OR = 0.82,
      95% CI = 0.74-0.92) conferred an increased susceptibility to CAD. Further
      subgroup analyses yielded similar positive results for -174G>C polymorphism in
      Asian and Caucasian populations, and for -572G>C polymorphism in Asian and
      African populations. In conclusion, our findings suggest that IL-6 -174G>C and 
      572G>C polymorphisms may serve as potential genetic markers of CAD.

PMID- 30230984
TI  - Synergistic Suppression of Melanoma Growth by a Combination of Natural dsRNA and
      Panaxadiolsaponins.
AB  - Melanoma is one of the most lethal skin malignancies in the world. Interferons
      (IFNs) have been also demonstrated in response to tumor cell and IFNs such as IFN
      alpha have been used for melanoma treatment. The long chain double-stranded RNA
      (dsRNA) (from a variety of nonviral sources) is a potent activator of the IFN
      system and an inducer of cell apoptosis. Panaxadiolsaponins (PDS) is a major
      Panax ginseng-derived active component with known antitumor activity and immune
      modulation. Here, we investigated a hypothesis that the combination of PDS and
      total natural dsRNA (as opposed to the synthetic dsRNA) will suppress tumor
      growth better than the individual agents. We have evaluated the antitumor and
      immunostimulatory effects of the combination of natural long chain dsRNA (derived
      from yeast) and PDS on melanoma cell line B16 and mice xenograft model. The
      underlying mechanisms of growth suppression were investigated by analyzing dsRNA
      activated pathways, apoptosis, and cell cycle. Natural dsRNA and PDS exert
      superior anticancer effects than either agent alone. Natural dsRNA and PDS
      combination might be a promising strategy for treating malignancies, including
      melanoma.

PMID- 30230986
TI  - Impaired sensorimotor control of the hand in congenital absence of functional
      muscle spindles.
AB  - Patients with Hereditary Sensory & Autonomic Neuropathy type III exhibit marked
      ataxia, including gait disturbances. We recently showed that functional muscle
      spindle afferents in the leg, recorded via intraneural microelectrodes inserted
      into the peroneal nerve, are absent in HSAN III, although large-diameter
      cutaneous afferents are intact. Moreover, there is a tight correlation between
      loss of proprioceptive acuity at the knee and the severity of gait impairment. We
      tested the hypothesis that manual motor performance is also compromised in HSAN
      III, attributed to the predicted absence of muscle spindles in the intrinsic
      muscles of the hand. Manual performance in the Purdue pegboard task was assessed
      in 12 individuals with HSAN III and 11 age-matched healthy controls. The mean
      (?SD) pegboard score (number of pins inserted in 30 s) was 8.1?1.9 and 8.6?1.8
      for the left and right hand respectively, significantly lower than the scores for
      the controls (15.0?1.3 and 16.0?1.1; p<0.0001). Performance was not improved
      after applying kinesiology tape over the joints of the hand. In five patients we
      inserted a tungsten microelectrode into the ulnar nerve at the wrist. No
      spontaneous or stretch-evoked muscle afferent activity could be identified in any
      of the 11 fascicles supplying intrinsic muscles of the hand, whereas rich tactile
      afferent activity could be recorded from four cutaneous fascicles. We conclude
      that functional muscle spindles are absent in the hand, and most likely absent in
      the long finger flexors and extensors, and that this largely accounts for the
      poor manual motor performance in HSAN III.

PMID- 30230985
TI  - Increased Serum MCP-1 Levels in Systemic Vasculitis Patients with Renal
      Involvement.
AB  - Monocyte chemotactic protein 1 (MCP-1) plays a significant role in inflammation
      pathways by affecting monocyte/macrophage migration, the number of monocytes and
      T lymphocytes, and osmosis. Inflammation is closely linked to various types of
      systematic vasculitis. Here we characterized serum MCP-1 levels in systemic
      vasculitis patients. This cross-sectional study included serum samples collected
      from 43 patients with systemic vasculitis and 43 healthy controls (HCs). Serum
      MCP-1 levels in the samples were measured using commercially available enzyme
      linked immunosorbent assay (ELISA) kits. Serum MCP-1 levels were significantly
      higher in patients with systemic vasculitis relative to HCs (parentheses indicate
      quartile values) [134.65 (73.74, 262.75) pg/mL versus 59.1 (37.41, 90.18) pg/mL,
      P < 0.001]. Furthermore, systemic vasculitis patients having renal involvement
      had significantly higher MCP-1 levels relative to patients without renal
      involvement [196.16 (104.41, 310.35) pg/mL versus 73.74 (41.24, 145.95) pg/mL, P
      = 0.001] and HCs [196.16 (104.41, 310.35) pg/mL versus 59.10 (37.41, 90.18)
      pg/mL, P < 0.001]. Serum MCP-1 levels in systemic vasculitis patients were
      positively correlated with serum creatinine levels (r = 0.387, P < 0.010) and
      with 24-h proteinuria (r = 0.404, P < 0.014). Receiver operating characteristic
      (ROC) analysis showed that the cutoff value for MCP-1 to distinguish systemic
      vasculitis from HCs was 72.73 pg/mg, and the area under the ROC curve was 0.772.
      The sensitivity and specificity were 76.7% and 72.1%, respectively. Serum MCP-1
      levels were significantly higher in patients with systemic vasculitis than in
      HCs, especially in patients with renal involvement. Thus, serum MCP-1 has the
      potential to be a biomarker for systemic vasculitis with renal involvement.

PMID- 30230987
TI  - Plan-based generalization shapes local implicit adaptation to opposing visuomotor
      transformations.
AB  - The human ability to use different tools demonstrates our capability of forming
      and maintaining multiple, context specific motor memories. Experimentally, this
      has been investigated in dual adaptation, where participants adjust their
      reaching movements to opposing visuomotor transformations. Adaptation in these
      paradigms occurs by distinct processes, such as strategies for each
      transformation or the implicit acquisition of distinct visuomotor mappings. While
      distinct, transformation-dependent aftereffects have been interpreted as support
      for the latter, they could reflect adaptation of a single visuomotor map, which
      is locally adjusted in different regions of the workspace. Indeed, recent studies
      suggest that explicit aiming strategies direct where in the workspace implicit
      adaptation occurs, thus potentially serving as a cue to enable dual adaptation.
      Disentangling these possibilities is critical to understanding how humans acquire
      and maintain motor memories for different skills and tools. We therefore
      investigated generalization of explicit and implicit adaptation to untrained
      movement directions after participants practiced two opposing cursor rotations,
      which were associated with the visual display being presented in the left or
      right half of the screen. Whereas participants learned to compensate for opposing
      rotations by explicit strategies specific to this visual workspace cue,
      aftereffects were not cue-sensitive. Instead, aftereffects displayed bimodal
      generalization patterns that appeared to reflect locally limited learning of both
      transformations. By varying target arrangements and instructions, we show that
      these patterns are consistent with implicit adaptation that generalizes locally
      around movement plans associated with opposing visuomotor transformations. Our
      findings show that strategies can shape implicit adaptation in a complex manner.

PMID- 30230983
TI  - Long Noncoding RNA Signatures Induced by Toll-Like Receptor 7 and Type I
      Interferon Signaling in Activated Human Plasmacytoid Dendritic Cells.
AB  - Long noncoding RNAs (lncRNAs) exhibit highly lineage-specific expression and act
      through diverse mechanisms to exert control over a wide range of cellular
      processes. lncRNAs can function as potent modulators of innate immune responses
      through control of transcriptional and posttranscriptional regulation of mRNA
      expression and processing. Recent studies have demonstrated that lncRNAs
      participate in the regulation of antiviral responses and autoimmune disease.
      Despite their emerging role as immune mediators, the mechanisms that govern
      lncRNA expression and function have only begun to be characterized. In this
      study, we explore the role of lncRNAs in human plasmacytoid dendritic cells
      (pDCs), which are critical sentinel sensors of viral infection and contribute to
      the development of autoimmune disease. Using genome-wide sequencing approaches,
      we dissect the contributions of Toll-like receptor 7 (TLR7) and type I interferon
      (IFN-I) in the regulation of coding and noncoding RNA expression in CAL-1 pDCs
      treated with R848 or IFNbeta. Functional enrichment analysis reveals both the
      unique and synergistic roles of TLR7 and IFN-I signaling in the orchestration of
      pDC function. These observations were consistent with primary cell immune
      responses elicited by detection of viral infection. We identified and
      characterized the conditional TLR7- and IFN-I-dependent regulation of 588
      lncRNAs. Dysregulation of these lncRNAs could significantly alter pDC maturation,
      IFN-I and inflammatory cytokine production, antigen presentation, costimulation
      or tolerance cues, turnover, or localization, all consequential events during
      viral infection or IFN-I-driven autoimmune diseases such as systemic lupus
      erythematosus. These findings demonstrate the differential responsiveness of
      lncRNAs to unique immune stimuli, uncover regulatory mechanisms of lncRNA
      expression, and reveal a novel and tractable platform for the study of lncRNA
      expression and function.

PMID- 30230988
TI  - Calcium stores regulate excitability in cultured rat hippocampal neurons.
AB  - Extracellular calcium ions support synaptic activity, but also reduce
      excitability of central neurons. In the present study, the effect of calcium on
      excitability was explored in cultured hippocampal neurons. CaCl2 injected by
      pressure in the vicinity of a neuron that is bathed only in MgCl2 as the main
      divalent cation, caused a depolarizing shift in action potential threshold and a
      reduction in excitability. This effect was not seen if the intracellular milieu
      consisted of Cs+ instead of K-gluconate as the main cation, or when it contained
      ruthenium red, which blocks release of calcium from stores. The suppression of
      excitability by calcium was mimicked by caffeine, and calcium store antagonists
      CPA or thapsigargin blocked this action. Neurons taken from synaptopodin (SP)-
      knockout mice show significantly reduced efficacy of calcium modulation of action
      potential threshold. Likewise, in Orai-1 knockdown cells calcium is less
      effective in modulating excitability of neurons. Activation of SK channels
      increased action potential threshold akin to that produced by calcium ions,
      whereas blockade of SK channels but not BK channels reduced the threshold for
      action potential discharge. These results indicate that calcium released from
      stores may suppress excitability of central neurons.

PMID- 30230989
TI  - Age-related differences in binaural masking level differences: Behavioral and
      electrophysiological evidence.
AB  - The effects of aging and stimulus configuration on binaural masking level
      differences (BMLDs) were measured behaviorally and electrophysiologically, using
      the frequency-following response (FFR) to target brainstem/midbrain encoding. The
      tests were performed in 15 younger normal-hearing (YNH; <30 yrs) and 15 older
      normal-hearing (ONH; >60 yrs) participants. The stimuli consisted of a 500-Hz
      target tone embedded in a narrowband (50-Hz bandwidth) or wideband (1500-Hz
      bandwidth) noise masker. The interaural phase conditions included NoSo (tone and
      noise presented interaurally in-phase), NoSpi (noise presented interaurally in
      phase and tone presented out-of-phase), and NpiSo (noise presented interaurally
      out-of-phase and tone presented in-phase) configurations. In the behavioral
      experiment, aging reduced the magnitude of the BMLD. The magnitude of the BMLD
      was smaller for the NoSo-NpiSo threshold difference compared to the NoSo-NoSpi
      threshold difference, and it was also smaller in narrowband compared to wideband
      conditions, consistent with previous measurements. In the electrophysiology
      experiment, older adults had reduced FFR magnitudes and smaller differences
      between configurations. The changes in FFR magnitude between the NoSo to NpiSo
      configurations were not significant for either bandwidth. The age-related
      reduction in FFR magnitudes suggests a temporal processing deficit, but no
      correlation was found between FFR magnitudes and behavioral BMLDs. Therefore,
      independent mechanisms may be contributing to the behavioral and neural deficits.
      Specifically, older adults had higher behavioral thresholds than younger adults
      for the NoSpi and NpiSo configurations, but had equivalent thresholds for the
      NoSo configuration. However, FFR magnitudes were reduced in older adults across
      all configurations.

PMID- 30230991
TI  - Functional Anatomy of Human Extraocular Muscles During Fusional Divergence.
AB  - We employed magnetic resonance imaging (MRI) to quantify human extraocular muscle
      contractility during centered target fusion, and fusional divergence repeated
      with each eye viewing monocularly at 20 cm through 8Delta, and at 400 cm through
      4Delta base in prism. Contractility, indicated by posterior partial volume (PPV)
      change, was analyzed in transverse rectus and in medial and lateral superior
      oblique (SO) muscle compartments, and by cross sectional area change in the
      inferior oblique (IO). At 20 cm, 3.1+/-0.5 degrees  (SEM) diverging eye abduction
      in 10 subjects was associated with 4.2+/-1.5% whole lateral rectus (LR) PPV
      increase (P<0.05), and 1.7+/-1.1% overall MR PPV decrease attributable to 3.1+/
      1.8% reduction in the superior compartment (P<0.025), without change in its
      inferior compartment, or in muscles of the aligned eye. At 400 cm, 2.2+/-0.5
      degrees  diverging eye abduction in 9 subjects was associated with 6.1+/-1.3%
      whole LR PPV increase (P<10-5) but no change in MR, with compartmentally similar
      relaxation in the LR and MR of the aligned eye. Unlike convergence, there were no
      IO or SO contractile changes for divergence to either target, nor any change in
      rectus pulley positions. Results confirm and extend to proximal divergence the
      unique role of the superior MR compartment, yet no MR role for far divergence. Co
      relaxation of aligned eye LR and MR combined with failure of MR relaxation during
      divergence is consistent with the limited behavioral range of divergence.

PMID- 30230990
TI  - Somatosensory Perceptual Training Enhances Motor Learning by Observing.
AB  - Action observation activates brain regions involved in sensory-motor control.
      Recent research has shown that action observation can also facilitate motor
      learning; observing a tutor undergoing motor learning results in functional
      plasticity within the motor system and gains in subsequent motor performance.
      However, the effects of observing motor learning extend beyond the motor domain.
      Converging evidence suggests that observation also results in somatosensory
      functional plasticity and somatosensory perceptual changes. This work has raised
      the possibility that the somatosensory system is also involved in motor learning
      that results from observation. Here we tested this hypothesis using a
      somatosensory perceptual training paradigm. If the somatosensory system is indeed
      involved in motor learning by observing, then improving subjects' somatosensory
      function before observation should enhance subsequent motor learning by
      observing. Subjects performed a proprioceptive discrimination task in which a
      robotic manipulandum moved the arm and subjects made judgments about the position
      of their hand. Subjects in a Trained Learning group received trial-by-trial
      feedback to improve their proprioceptive perception. Subjects in an Untrained
      Learning group performed the same task without feedback. All subjects then
      observed a learning video showing a tutor adapting her reaches to a left force
      field. Subjects in the Trained Learning group, who had superior proprioceptive
      acuity prior to observation, benefited more from observing learning than subjects
      in the Untrained Learning group. Improving somatosensory function can therefore
      enhance subsequent observation-related gains in motor learning. This study
      provides further evidence in favor of the involvement of the somatosensory system
      in motor learning by observing.

PMID- 30230993
TI  - Single-cell responses to three-dimensional structure in a functionally-defined
      patch in macaque area TEO.
AB  - Both dorsal and ventral visual pathways harbor several areas sensitive to
      gradients of binocular disparity (i.e. higher-order disparity). While a wealth of
      information exists about disparity processing in early visual areas (V1, V2, and
      V3) as well as in end-stage areas TE in the ventral stream and the Anterior
      Intraparietal area (AIP) in the dorsal stream, little is known about mid-level
      area TEO in the ventral pathway. We recorded single unit responses to disparity
      defined curved stimuli in a functional Magnetic Resonance Imaging (fMRI)
      activation elicited by curved surfaces compared to flat surfaces in the macaque
      area TEO. This fMRI activation contained a small proportion of disparity
      selective neurons, with very few of them second-order disparity selective.
      Overall, this population of TEO neurons did not preserve its 3D-structure
      selectivity across positions in depth, indicating a lack of higher-order
      disparity selectivity, but showed stronger responses to flat surfaces than to
      curved surfaces, as predicted by the fMRI experiment. The receptive fields of the
      responsive TEO cells were relatively small and generally foveal. A linear Support
      Vector Machine classifier showed that this population of disparity-selective TEO
      neurons contains reliable information about the sign of curvature and the
      position in depth of the stimulus.

PMID- 30230992
TI  - Effects of the swimming exercise on the extinction of fear memory in rats.
AB  - We investigated the relation between swimming exercise and fear memory
      extinction. Rats that performed regular swimming exercise over six weeks
      underwent a fear conditioning. Twenty-eight days later, they were submitted to
      extinction tests. Swimming rats had enhanced extinction process throughout the 5
      days of the extinction test when compared to sedentary ones (Exercise vs. Fear
      Conditioning vs. Test days interaction effect. This suggests that the swimming
      exercise accelerated the process of aversive memory extinction, reducing the
      expression of conditioned fear behavior. These results encourage further studies
      addressing the anxiolytic effects of exercise, with potential implications for
      anxiety disorders such as post-traumatic stress disorder.

PMID- 30230994
TI  - The Bislett Effect and Telemedicine.

PMID- 30230995
TI  - The Water Mass Transformation Framework for Ocean Physics and Biogeochemistry.
AB  - The water mass transformation (WMT) framework weaves together circulation,
      thermodynamics, and biogeochemistry into a description of the ocean that
      complements traditional Eulerian and Lagrangian methods. In so doing, a WMT
      analysis renders novel insights and predictive capabilities for studies of ocean
      physics and biogeochemistry. In this review, we describe fundamentals of the WMT
      framework and illustrate its practical analysis capabilities. We show how it
      provides a robust methodology to characterize and quantify the impact of physical
      processes on buoyancy and other thermodynamic fields. We also detail how to
      extend WMT to insightful analysis of biogeochemical cycles. Expected final online
      publication date for the Annual Review of Marine Science Volume 11 is January 3,
      2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised
      estimates.

PMID- 30230996
TI  - Evolution of 1, 3, 5-trisubstituted bipyrazole scaffold based platinum(II)
      complexes as a biological active agent.
AB  - Square planar mononuclear platinum(II) complexes having general formula
      [Pt(Ln)Cl2], (where, Ln = L1-4) were synthesized with neutral bidentate
      heterocyclic 1,3,5-trisubstituted bipyrazole based ligands. The synthesized
      compounds were characterized by physicochemical method such as TGA, molar
      conductance, micro-elemental analysis and magnetic moment, and spectroscopic
      method such as, FT-IR, UV-vis, 1H NMR, 13C NMR and mass spectrometry. Biological
      applications of the compounds were carried out using in vitro brine shrimp
      lethality bioassay, in vitro antimicrobial study against five different
      pathogens, and cellular level cytotoxicity against Schizosaccharomyces pombe (S.
      Pombe) cells. Pt(II) complexes were tested for DNA interaction activities using
      electronic absorption titration, viscosity measurements study, fluorescence
      quenching technique and molecular docking assay. Binding constants (Kb) of
      ligands and complexes were observed in the range of 0.23-1.07 * 105 M-1 and 0.51
      3.13 * 105 M-1, respectively. Pt(II) complexes (I-IV) display an excellent
      binding tendency to biomolecule (DNA) and possess comparatively high binding
      constant (Kb) values than the ligands. The DNA binding study indicate partial
      intercalative mode of binding in complex-DNA. The gel electrophoresis activity
      was carried out to examine DNA nuclease property of pUC19 plasmid DNA.

PMID- 30230997
TI  - Case 258: Granulomatous Prostatitis.
AB  - History A 68-year-old man with a remote history of a previously resected high
      grade urothelial carcinoma in the renal pelvis was being observed and was
      undergoing urologic treatment for recurrent low-grade urothelial carcinoma of the
      bladder. During his most recent evaluation, he reported no specific symptoms and
      denied experiencing hematuria, dysuria, or abdominal pain. At routine
      surveillance MRI of the abdomen and pelvis (images not shown), a lesion was noted
      in the peripheral zone of the prostate gland. The prostate-specific antigen level
      was elevated (7.51 ng/mL [normal range, 0.00-4.00 ng/mL]). The patient had no
      family history of prostate cancer and had never undergone prostate biopsy. MRI of
      the prostate with an endorectal coil was subsequently performed.

PMID- 30230998
TI  - Case 262.
AB  - History A 17-year-old white male adolescent was re-evaluated for a withheld
      cardiac condition initially detected during prenatal imaging at an outside
      institution. He had previously experienced intermittent episodes of shortness of
      breath, chest pain, and palpitations with exertion, but more recently he had been
      asymptomatic. He had no other comorbidities and no family history of congenital
      heart disease, cardiomyopathy, arrhythmia, or sudden cardiac death. At physical
      examination, the patient had a grade II/IV rumbling systolic murmur best heard at
      the left upper sternal border. Otherwise, cardiovascular and other physical
      examination findings were normal. An electrocardiogram showed sinus bradycardia
      and nonspecific T wave changes. A graded exercise stress test was normal. Cardiac
      MRI was performed without and with gadolinium-based contrast material ( Figs 1 -
      3 ). Multiple echocardiograms obtained since birth, cardiac MR images obtained 2
      and 4 years earlier ( Fig 4 ), and nongated CT images obtained with iodinated
      contrast material to evaluate trauma 8 years prior ( Fig 5 ) showed findings
      similar to those of the current examination. Prior chest radiographs (not shown)
      were normal, and angiography performed when the patient was 4 years old revealed
      normal coronary arteries. [Figure: see text][Figure: see text][Figure: see
      text][Figure: see text][Figure: see text][Figure: see text][Figure: see text].

PMID- 30230999
TI  - Mate Preferences and Their Behavioral Manifestations.
AB  - Evolved mate preferences comprise a central causal process in Darwin's theory of
      sexual selection. Their powerful influences have been documented in all sexually
      reproducing species, including in sexual strategies in humans. This article
      reviews the science of human mate preferences and their myriad behavioral
      manifestations. We discuss sex differences and sex similarities in human sexual
      psychology, which vary according to short-term and long-term mating contexts. We
      review context-specific shifts in mating strategy depending on individual,
      social, and ecological qualities such as mate value, life history strategy, sex
      ratio, gender economic inequality, and cultural norms. We review the empirical
      evidence for the impact of mate preferences on actual mating decisions. Mate
      preferences also dramatically influence tactics of mate attraction, tactics of
      mate retention, patterns of deception, causes of sexual regret, attraction to
      cues to sexual exploitability, attraction to cues to fertility, attraction to
      cues to resources and protection, derogation of competitors, causes of breakups,
      and patterns of remarriage. We conclude by articulating unresolved issues and
      offer a future agenda for the science of human mating, including how humans
      invent novel cultural technologies to better implement ancient sexual strategies
      and how cultural evolution may be dramatically influencing our evolved mating
      psychology. Expected final online publication date for the Annual Review of
      Psychology Volume 70 is January 4, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30231000
TI  - A Mechanistic Framework for Explaining Audience Design in Language Production.
AB  - Audience design refers to the situation in which speakers fashion their
      utterances so as to cater to the needs of their addressees. In this article, a
      range of audience design effects are reviewed, organized by a novel cognitive
      framework for understanding audience design effects. Within this framework,
      feedforward (or one-shot) production is responsible for feedforward audience
      design effects, or effects based on already known properties of the addressee
      (e.g., child versus adult status) or the message (e.g., that it includes meanings
      that might be confusable). Then, a forward modeling approach is described,
      whereby speakers independently generate communicatively relevant features to
      predict potential communicative effects. This can explain recurrent processing
      audience design effects, or effects based on features of the produced utterance
      itself or on idiosyncratic features of the addressee or communicative situation.
      Predictions from the framework are delineated. Expected final online publication
      date for the Annual Review of Psychology Volume 70 is January 4, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30231001
TI  - The Caring Continuum: Evolved Hormonal and Proximal Mechanisms Explain Prosocial
      and Antisocial Extremes.
AB  - Implicit in the longstanding disagreements about whether humans' fundamental
      nature is predominantly caring or callous is an assumption of uniformity. This
      article reviews evidence that instead supports inherent variation in caring
      motivation and behavior. The continuum between prosocial and antisocial extremes
      reflects variation in the structure and function of neurohormonal systems
      originally adapted to motivate parental care and since repurposed to support
      generalized forms of care. Extreme social behaviors such as extraordinary acts of
      altruism and aggression can often be best understood as reflecting variation in
      the neural systems that support care. A review of comparative, developmental, and
      neurobiological research finds consistent evidence that variations in caring
      motivations and behavior reflect individual differences in sensitivity to cues
      that signal vulnerability and distress and in the tendency to generalize care
      outward from socially close to distant others. The often complex relationships
      between caring motivation and various forms of altruism and aggression are
      discussed. Expected final online publication date for the Annual Review of
      Psychology Volume 70 is January 4, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30231002
TI  - Personality Across the Life Span.
AB  - Trait stability and maturation are fundamental principles of contemporary
      personality psychology and have been shown to hold across many cultures. However,
      it has proven difficult to move beyond these general findings to a detailed
      account of trait development. There are pervasive and unexplained inconsistencies
      across studies that may be due to (a) insufficient attention to measurement
      error, (b) subtle but age-sensitive differences in alternative measures of the
      same trait, or (c) different perspectives reflected in self-reports and observer
      ratings. Multiscale, multimethod-and ideally multinational-studies are needed.
      Several hypotheses have been proposed to account for trait stability and change,
      but supporting evidence is currently weak or indirect; trait development is a
      fertile if sometimes frustrating field for theory and research. Beyond traits,
      there are approaches to personality development that are of interest to students
      of adult development, and these may be fruitfully addressed from a trait
      perspective. Expected final online publication date for the Annual Review of
      Psychology Volume 70 is January 4, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30231003
TI  - Computer Games in Education.
AB  - Visionaries offer strong claims for the educational benefits of computer games,
      but there is a need to test those claims with rigorous scientific research and
      ground them in evidence-based theories of how people learn. Three genres of game
      research are (a) value-added research, which compares the learning outcomes of
      groups that learn academic material from playing a base version of a game to the
      outcomes of those playing the same game with one feature added; (b) cognitive
      consequences research, which compares improvements in cognitive skills of groups
      that play an off-the-shelf game to the skill improvements of those who engage in
      a control activity; and (c) media comparison research, which compares the
      learning outcomes of groups that learn academic material in a game to the
      outcomes of those who learn with conventional media. Value-added research
      suggests five promising features to include in educational computer games:
      modality, personalization, pretraining, coaching, and self-explanation. Cognitive
      consequences research suggests two promising approaches to cognitive training
      with computer games: using first-person shooter games to train perceptual
      attention skills and using spatial puzzle games to train two-dimensional mental
      rotation skills. Media comparison research suggests three promising areas where
      games may be more effective than conventional media: science, mathematics, and
      second-language learning. Future research is needed to pinpoint the cognitive,
      motivational, affective, and social processes that underlie learning with
      educational computer games. Expected final online publication date for the Annual
      Review of Psychology Volume 70 is January 4, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30231004
TI  - e-Health and multiple sclerosis: An update.
AB  - e-Health (or digital healthcare) is becoming increasingly relevant in multiple
      sclerosis (MS) clinical management. We aim to review and discuss current status
      and future perspective of e-health in people with multiple sclerosis (pwMS). The
      first part of this review describes how information on MS can be conveyed through
      the Web and digital media. The second part illustrates recent advances in digital
      technology that can improve clinical management and in motor and cognitive
      rehabilitation of pwMS. Finally, this review advocates future development of the
      "digital case manager" as a new figure to coordinate clinical management and care
      of pwMS. The digital revolution is changing the medical approach to MS in terms
      of information conveying and sharing, rehabilitation, and healthcare management.

PMID- 30231005
TI  - Development of a wheeled walker braking device using the four-bar mechanism.
AB  - The elderly population in many countries has been rising rapidly, and falls are a
      serious event many elderly people experience. Assistive equipment is actively
      used to reduce falls among elderly people. Popular types of assistive equipment
      include canes, electric wheelchairs, and wheeled walkers. Wheeled walkers support
      the body of elderly people, making their gait comfortable as they age or recover
      from injuries. Wheeled walkers may be equipped with hand brakes; however, frail
      older people may experience difficulty using such hand brakes, as they require
      force to operate. Thus, in the present study, a braking method using a wire
      connected to a user's belt or clothes was designed and implemented; if the
      tension of the wire connecting the safety device and the user exceeds a critical
      value, the wheeled walker brakes, which can prevent the rapid motion of walkers.
      Two feasibility tests of the wheeled walker with the braking device were
      conducted: one with 10 healthy adults in their 20s and the other with 10 elderly
      people over 65 years of age; the tests measured the braking time and speed
      control using a speed measuring device. The results of the first and second
      feasibility tests demonstrated that the average braking time of participants was
      50.3 ms and 50.7 ms, respectively. All participants in the feasibility tests
      succeeded in the speed control test. Thus, based on the results, the braking
      device on the wheeled walker worked properly.

PMID- 30231006
TI  - Electrically evoked wrist extensor muscle fatigue throughout repetitive motion as
      measured by mechanomyography and near-infrared spectroscopy.
AB  - Repetitive electrically-evoked muscle contraction leads to accelerated muscle
      fatigue. This study assessed electrically-evoked fatiguing muscle with changes to
      mechanomyography root mean square percentage (%RMS-MMG) and tissue saturation
      index (%TSI) in extensor carpi radialis. Forty healthy volunteers (n=40)
      performed repetitive electrical-evoked wrist extension to fatigue and results
      were analyzed pre- and post-fatigue, i.e. 50% power output (%PO) drop. Responses
      of %PO, %TSI and %RMS-MMG were correlated while the relationships between %RMS
      MMG and %TSI were investigated using linear regression. The %TSI for both groups
      were negatively correlated with declining %PO as the ability of the muscle to
      take up oxygen became limited due to fatigued muscle. The %RMS-MMG behaved in two
      different patterns post-fatigue against declining %PO whereby; (i) group A showed
      positive correlation (%RMS-MMG decreased) throughout the session and (ii) group B
      demonstrated negative correlation (%RMS-MMG increased) with declining %PO until
      the end of the session. Regression analysis showed %TSI was inversely
      proportional to %RMS-MMG during post-fatigue in group A. Small gradients in both
      groups suggested that %TSI was not sensitive to the changes in %RMS-MMG and they
      were mutually exclusive. Most correlation and regression changed significantly
      post-fatigue indicating that after fatigue, the condition of muscle had changed
      mechanically and physiologically.

PMID- 30231007
TI  - Optical measurement of the corneal oscillation for the determination of the
      intraocular pressure.
AB  - Motivation Glaucoma is currently the most common irreversible cause of blindness
      worldwide. A significant risk factor is an individually increased intraocular
      pressure (IOP). A precise measurement method is needed to determine the IOP in
      order to support the diagnosis of the disease and to monitor the outcome of the
      IOP reduction as a medical intervention. A handheld device is under development
      with which the patient can perform self-measurements outside the clinical
      environment. Method For the measurement principle of the self-tonometer the eye
      is acoustically excited to oscillate, which is analyzed and attributed to the
      present IOP. In order to detect the corneal oscillation, an optical sensor is
      required which meets the demands of a compact, battery driven self-tonometer. A
      combination of an infrared diode and a phototransistor provides a high-resolution
      measurement of the corneal oscillation in the range of 10 MUm-150 MUm, which is
      compared to a reference sensor in the context of this study. By means of an
      angular arrangement of the emitter and the detector, the degree of reflected
      radiation of the cornea can be increased, allowing a measurement with a high
      signal-to-noise ratio. Results By adjusting the angle of incidence between the
      detector and the emitter, the signal-to-noise ratio was improved by 40 dB which
      now allows reasonable measurements of the corneal oscillation. For low amplitudes
      (10 MUm) the signal-to-noise ratio is 10% higher than that of the commercial
      reference sensor. On the basis of amplitude variations at different IOP levels,
      the estimated standard uncertainty amounts to <0.5 mm Hg in the physiological
      pressure range with the proposed measuring approach. Conclusion With a compact
      and cost-effective approach, that suits the requirements for a handheld self
      tonometer, the corneal oscillation can be detected with high temporal resolution.
      The cross-sensitivity of the sensor concept concerning a distance variation can
      be reduced by adding a distance sensor. Existing systematic influences of corneal
      biomechanics will be integrated in the sensor concept as a consecutive step.

PMID- 30231008
TI  - Serum cytokines, adipokines and ferritin for non-invasive assessment of liver
      fibrosis in chronic liver disease: a systematic review.
AB  - Chronic liver disease (CLD) is a major health problem worldwide. Non-alcoholic
      fatty liver disease (NAFLD), chronic hepatitis C (CHC), chronic hepatitis B
      (CHB), and alcoholic liver disease (ALD) are the most common etiologies of CLD.
      Liver biopsy is the gold standard for assessment of liver fibrosis, however, it
      is an invasive method. This review attempts to evaluate the usefulness of serum
      adiponectin, serum leptin, serum ferritin, serum transforming growth factor-beta1
      (TGF-beta1), and serum platelet derived growth factor-BB (PDGF-BB) as non
      invasive markers in the diagnosis of liver fibrosis/cirrhosis. A systematic
      search in MEDLINE, Web of Science, Scopus, and local databases was performed to
      identify articles published in English or Persian as of November 2017. Studies
      conducted among CLD patients, with biopsy proven fibrosis/cirrhosis, and
      providing sufficient details of patients' clinicopathological characteristics
      were included. In the 95 studies included, there were a total of 15,548 CLD
      patients. More than 83% of studies were carried out in Asia and Europe. The
      relationship between liver fibrosis/cirrhosis and serum levels of ferritin,
      adiponectin, leptin, TGF-beta1, and PDGF-BB was assessed in 42, 33, 27, nine, and
      three studies, respectively. Serum levels of the markers, particularly ferritin,
      could successfully predict liver fibrosis/cirrhosis, however, these data might
      not be clinically replicated and further studies are needed.

PMID- 30231009
TI  - Cannabinoids determination in bronchoalveolar lavages of cannabis smokers with
      lung disease.
AB  - Background Cannabis smoke affects the lungs similarly to tobacco smoke, causing
      symptoms such as increased cough, sputum, hyperinflation and chronic bronchitis.
      Chronic use can also cause serious lung diseases and airway obstruction. We
      developed and validated a method for the identification and quantification of
      cannabinol (CBN), cannabidiol (CBD), Delta-9-tetrahydrocannabinol (THC) and its
      metabolites 11-hydroxy-THC (11-OH-THC) and 11-nor-9-carboxy-THC (THC-COOH) in
      bronchoalveolar lavages (BALs) from hospitalized former or current tobacco
      smoking patients with lung disease and a long history of cannabis consumption and
      limited current tobacco use. Methods For the extraction of cannabinoids from
      BALs, a 1 mL sample was added with 300 uL of 0.1 N NaOH and 3 mL of hexane/ethyl
      acetate (9:1). The solvent was then evaporated to dryness. Trimethylsilyl
      derivatives were prepared and then analyzed by gas chromatography/mass
      spectrometry. Results The method was linear for the analytes under investigation
      with coefficients of determination of at least 0.99. Absolute analytical recovery
      was always better than 80%, imprecision and inaccuracy was always under 15%. Six
      cases out of 15 were positive for THC, CBN and CBD. In two BALs samples, the
      presence of 11-OH-THC was also measured while THC-COOH was not detected. In the
      six positive cases, the last cannabis smoking occurred in the previous 2-14 days.
      Conclusions This is the first time that cannabinoids have been detected in BALs,
      demonstrating the presence of a drug with its metabolites in a target organ of
      consumers who present with a lung disease. This occurrence let us hypothesize a
      role of cannabinoids in the development of the disease and prompted an
      investigation on possible associations between cannabis smoking and clinical
      outcomes in patients with lung disease and eventually evaluate a cytotoxic effect
      of cannabinoids themselves.

PMID- 30231010
TI  - Blinding or information control in diagnosis: could it reduce errors in clinical
      decision-making?
AB  - Background Clinical medicine has long recognized the potential for cognitive bias
      in the development of new treatments, and in response developed a tradition of
      blinding both clinicians and patients to address this specific concern. Although
      cognitive biases have been shown to exist which impact the accuracy of clinical
      diagnosis, blinding the diagnostician to potentially misleading information has
      received little attention as a possible solution. Recently, within the forensic
      sciences, the control of contextual information (i.e. information apart from the
      objective test results) has been studied as a technique to reduce errors. We
      consider the applicability of this technique to clinical medicine. Content This
      article briefly describes the empirical research examining cognitive biases
      arising from context which impact clinical diagnosis. We then review the recent
      awakening of forensic sciences to the serious effects of misleading information.
      Comparing the approaches, we discuss whether blinding to contextual information
      might (and in what circumstances) reduce clinical errors. Summary and outlook
      Substantial research indicates contextual information plays a significant role in
      diagnostic error and conclusions across several medical specialties. The forensic
      sciences may provide a useful model for the control of potentially misleading
      information in diagnosis. A conceptual analog of the forensic blinding process
      (the "agnostic" first reading) may be applicable to diagnostic investigations
      such as imaging, microscopic tissue examinations and waveform recognition. An
      "agnostic" approach, where the first reading occurs with minimal clinical
      referral information, but is followed by incorporation of the clinical history
      and reinterpretation, has the potential to reduce errors.

PMID- 30231011
TI  - Comparison of serum 25-hydroxyvitamin D levels between radioimmunoassay and
      liquid chromatography-tandem mass spectrometry in infants and postpartum women.
AB  - Background Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become
      the gold standard for the measurement of serum 25-hydroxyvitamin D (25(OH)D)
      levels instead of the conventional method, radioimmunoassay (RIA). However, there
      was no study that compared RIA and LC-MS/MS for measuring serum 25(OH)D levels in
      infants and their mothers. The aim of this study was to assess the agreement of
      RIA and LC-MS/MS for measuring the serum levels in infants and postpartum women.
      Methods This study enrolled 70 preterm infants, 113 term infants (134 samples),
      and 120 postpartum women. Serum concentration of 25(OH)D was measured by RIA and
      LC-MS/MS. We evaluated the correlation between RIA and LC-MS/MS. Also, we
      evaluated the bias between RIA and LC-MS/MS using Bland-Altman analysis. Results
      Sixty percent of preterm infants had serum 25(OH)D levels below the lower limit
      of quantification (LOQ) (4 ng/mL) and 90% of them were classified as vitamin D
      deficient. The serum 25(OH)D levels measured by RIA were significantly correlated
      with those measured by LC-MS/MS in all groups. According to the Bland-Altman
      plot, the serum 25(OH)D levels of infants measured by RIA had constant positive
      bias (mean+/-standard deviation [SD] [95% confidence interval, CI], preterm:
      +4.8+/- 2.4 ng/mL [4.2-5.4], term: +5.8+/-4.0 [5.1-6.5]) and proportional bias
      (preterm: r=0.44, p<0.01, term: r=0.50, p<0.01) compared with LC-MS/MS. The serum
      25(OH)D levels of postpartum women measured by RIA had constant positive bias
      compared with LC-MS/MS, but no proportional bias was found. Conclusions RIA
      demonstrated falsely high 25(OH)D levels when used for infants and postpartum
      women.

PMID- 30231012
TI  - Vitamin A and beta-carotene in pregnant and breastfeeding post-bariatric women in
      an urban population.
AB  - Background As breastfeeding awareness and social acceptance are increased,
      maternal nutritional deficiency requires more investigation. Methods A
      prospective cohort study was conducted to determine if vitamin A deficiency is
      more common in pregnant, lactating post-bariatric surgery women in an inner city
      population. Antepartum, women after bariatric surgery and controls with no
      history of malabsorption were recruited. Third trimester, postpartum maternal
      blood and cord blood were collected as well as three breast milk samples:
      colostrum, transitional and mature milk. A nutritional survey of diet was
      completed. Each serum sample was analyzed for total retinol and beta-carotene;
      breast milk samples were analyzed for retinol and retinyl esters, total retinol
      and beta-carotene. Results Fifty-three women after bariatric surgery and 66
      controls were recruited. Postpartum serum retinol was significantly higher in
      women after bariatric surgery in the univariate analysis (P<0.0001) and confirmed
      in the multiple linear mixed model (P=0.0001). Breast milk colostrum retinol and
      transitional milk total retinol were significantly greater in the bariatric
      surgery group in the univariate analysis (P=0.03 and P=0.02, respectively), but
      not after adjusting for confounders. Serum beta-carotene in the third trimester
      and postpartum were lower (P<0.0001 and P=0.003, respectively) in the bariatric
      surgery group but not after adjusting for confounders. Vitamin A deficiency was
      high in both groups in serum and breast milk samples. Conclusions Nutritional
      deficiencies in breastfeeding women after bariatric surgeries may in fact be less
      common than in control women in an inner city.

PMID- 30231013
TI  - Mechanisms of death in structurally normal stillbirths.
AB  - Objectives To investigate mechanisms of in utero death in normally formed fetuses
      by measuring amniotic fluid (AF) biomarkers for hypoxia (erythropoietin [EPO]),
      myocardial damage (cardiac troponin I [cTnI]) and brain injury (glial fibrillary
      acidic protein [GFAP]), correlated with risk factors for fetal death and
      placental histopathology. Methods This retrospective, observational cohort study
      included intrauterine deaths with transabdominal amniocentesis prior to induction
      of labor. Women with a normal pregnancy and an indicated amniocentesis at term
      were randomly selected as controls. AF was assayed for EPO, cTnI and GFAP using
      commercial immunoassays. Placental histopathology was reviewed, and CD15
      immunohistochemistry was used. Analyte concentrations >90th centile for controls
      were considered "raised". Raised AF EPO, AF cTnI and AF GFAP concentrations were
      considered evidence of hypoxia, myocardial and brain injury, respectively.
      Results There were 60 cases and 60 controls. Hypoxia was present in 88% (53/60),
      myocardial damage in 70% (42/60) and brain injury in 45% (27/60) of fetal deaths.
      Hypoxic fetuses had evidence of myocardial injury, brain injury or both in 77%
      (41/53), 49% (26/53) and 13% (7/53) of cases, respectively. Histopathological
      evidence for placental dysfunction was found in 74% (43/58) of these cases.
      Conclusions Hypoxia, secondary to placental dysfunction, was found to be the
      mechanism of death in the majority of fetal deaths among structurally normal
      fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial
      or both brain and myocardial injuries in utero. Hypoxic myocardial injury was an
      attributable mechanism of death in 70% of the cases. Non-hypoxic cases may be
      caused by cardiac arrhythmia secondary to a cardiac conduction defect.

PMID- 30231015
TI  - Phenotype of Vascular Smooth Muscle Cells (VSMCs) Is Regulated by miR-29b by
      Targeting Sirtuin 1.
AB  - BACKGROUND Phenotypic switch of vascular smooth muscle cells (VSMCs) participates
      in the etiology of various vascular diseases. It has been proved that microRNAs
      (miRNAs) serve as crucial regulators of functions of VSMCs. This study aimed to
      discover how miR-29b regulates the transformation of VSMCs phenotypes in mice.
      MATERIAL AND METHODS Primary VSMCs of aorta in mice were cultured in DMEM medium.
      A series of experiments involving transfection of oligonucleotides in cultured
      VSMCs, quantitative reverse transcription PCR (qRT-PCR), luciferase reporter
      assay, and Western blotting analysis were performed in this study. RESULTS We
      found that in VSMCs cultured in presence of stimulator, platelet-derived growth
      factor-BB (PDGF-BB), miR-29b was upregulated significantly and expressions of
      VSMC-phenotype-related genes (alpha-SMA, calponin, and SM-MHC) were regulated by
      miR-29b. Moreover, through downregulation of sirtuin 1 (SIRT1), miR-29b affects
      phenotypic transformation of VSMCs. Luciferase report assay identified a
      significant increase of SIRT1 3'-UTR activity in treatment with miR-29b
      inhibitor, which, however, was reversed in the presence of miR-29b mimic.
      Suppression of miR-29b reversed the activation of NF-kappaB induced by PDGF-BB in
      VSMCs. CONCLUSIONS We concluded that miR-29b is an important regulator in the
      PDGF-BB-mediated VSMC phenotypic transition by targeting SIRT1. Interventions
      aimed at miR-29b may be promising in treating numerous proliferative vascular
      disorders.

PMID- 30231014
TI  - Assessing genome-wide significance for the detection of differentially methylated
      regions.
AB  - DNA methylation plays an important role in human health and disease, and methods
      for the identification of differently methylated regions are of increasing
      interest. There is currently a lack of statistical methods which properly address
      multiple testing, i.e. control genome-wide significance for differentially
      methylated regions. We introduce a scan statistic (DMRScan), which overcomes
      these limitations. We benchmark DMRScan against two well established methods
      (bumphunter, DMRcate), using a simulation study based on real methylation data.
      An implementation of DMRScan is available from Bioconductor. Our method has
      higher power than alternative methods across different simulation scenarios,
      particularly for small effect sizes. DMRScan exhibits greater flexibility in
      statistical modeling and can be used with more complex designs than current
      methods. DMRScan is the first dynamic approach which properly addresses the
      multiple-testing challenges for the identification of differently methylated
      regions. DMRScan outperformed alternative methods in terms of power, while
      keeping the false discovery rate controlled.

PMID- 30231017
TI  - Correction: Comparative genomics and the nature of placozoan species.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.2005359.].

PMID- 30231018
TI  - Reconstruction of the socio-semantic dynamics of political activist Twitter
      networks-Method and application to the 2017 French presidential election.
AB  - BACKGROUND: Digital spaces, and in particular social networking sites, are
      becoming increasingly present and influential in the functioning of our
      democracies. In this paper, we propose an integrated methodology for the data
      collection, the reconstruction, the analysis and the visualization of the
      development of a country's political landscape from Twitter data. METHOD: The
      proposed method relies solely on the interactions between Twitter accounts and is
      independent of the characteristics of the shared contents such as the language of
      the tweets. We validate our methodology on a case study on the 2017 French
      presidential election (60 million Twitter exchanges between more than 2.4 million
      users) via two independent methods: the comparison between our automated
      political categorization and a human categorization based on the evaluation of a
      sample of 5000 profiles descriptions; the correspondence between the
      reconfigurations detected in the reconstructed political landscape and key
      political events reported in the media. This latter validation demonstrated the
      ability of our approach to accurately reflect the reconfigurations at play in the
      off-line political scene. RESULTS: We built on this reconstruction to give
      insights into the opinion dynamics and the reconfigurations of political
      communities at play during a presidential election. First, we propose a
      quantitative description and analysis of the political engagement of members of
      political communities. Second, we analyze the impact of political communities on
      information diffusion and in particular on their role in the fake news phenomena.
      We measure a differential echo chamber effect on the different types of political
      news (fake news, debunks, standard news) caused by the community structure and
      emphasize the importance of addressing the meso-structures of political networks
      in understanding the fake news phenomena. CONCLUSIONS: Giving access to an
      intermediate level, between sociological surveys in the field and large
      statistical studies (such as those conducted by national or international
      organizations) we demonstrate that social networks data make it possible to
      qualify and quantify the activity of political communities in a multi-polar
      political environment; as well as their temporal evolution and reconfiguration,
      their structure, their alliance strategies and their semantic particularities
      during a presidential campaign through the analysis of their digital traces. We
      conclude this paper with a comment on the political and ethical implications of
      the use of social networks data in politics. We stress the importance of
      developing social macroscopes that will enable citizens to better understand how
      they collectively make society and propose as example the "Politoscope", a
      macroscope that delivers some of our results in an interactive way.

PMID- 30231016
TI  - Anthropoid primate-specific retroviral element THE1B controls expression of CRH
      in placenta and alters gestation length.
AB  - Pregnancy and parturition are intricately regulated to ensure successful
      reproductive outcomes. However, the factors that control gestational length in
      humans and other anthropoid primates remain poorly defined. Here, we show the
      endogenous retroviral long terminal repeat transposon-like human element 1B
      (THE1B) selectively controls placental expression of corticotropin-releasing
      hormone (CRH) that, in turn, influences gestational length and birth timing.
      Placental expression of CRH and subsequently prolonged gestational length were
      found in two independent strains of transgenic mice carrying a 180-kb human
      bacterial artificial chromosome (BAC) DNA that contained the full length of CRH
      and extended flanking regions, including THE1B. Restricted deletion of THE1B
      silenced placental CRH expression and normalized birth timing in these transgenic
      lines. Furthermore, we revealed an interaction at the 5' insertion site of THE1B
      with distal-less homeobox 3 (DLX3), a transcription factor expressed in placenta.
      Together, these findings suggest that retroviral insertion of THE1B into the
      anthropoid primate genome may have initiated expression of CRH in placental
      syncytiotrophoblasts via DLX3 and that this placental CRH is sufficient to alter
      the timing of birth.

PMID- 30231020
TI  - Pre-existing technological core and roots for the CRISPR breakthrough.
AB  - This paper applies objective methods to explore the technological origins of the
      widely acclaimed CRISPR breakthrough in the technological domain of genome
      engineering. Previously developed patent search techniques are first used to
      recover a set of patents that well-represent the genome editing domain before
      CRISPR. Main paths are then determined from the citation network associated with
      this patent set allowing identification of the three major knowledge
      trajectories. The most significant of these trajectories for CRISPR involves the
      core of genome editing with less significant trajectories involving cloning and
      endonuclease specific developments. The major patents on the core trajectory are
      consistent with qualitative expert knowledge of the topical area. A second set of
      patents that we call the CRISPR roots are obtained by finding the patents
      directly cited by the recent CRISPR patents along with patents cited by that set
      of patents. We find that the CRISPR roots contain 8 key patents from the genome
      engineering main path associated with restriction endonucleases and the expected
      strong connection of CRISPR to prior genome editing technology such as Zn finger
      nucleases. Nonetheless, analysis of the full CRISPR roots shows that a very wide
      array of technological knowledge beyond genome engineering has contributed to
      achieving the CRISPR breakthrough. Such breadth in origins is not surprising
      since "spillover" is generally perceived as important and previous qualitative
      studies of CRISPR have shown not only technological breadth in origins but
      scientific breadth as well. In addition, we find that the estimated rate of
      functional performance improvement of the CRISPR roots set is about 9% per year
      compared to the genome engineering set (~4% per year). These estimates indicate
      below average rates of improvement and may indicate that CRISPR (and perhaps yet
      undiscovered) genome engineering developments could evolve in effectiveness over
      an upcoming long rather than short time period.

PMID- 30231019
TI  - Combined exposure to lifting and psychosocial strain at work and adverse
      pregnancy outcomes-A study in the Danish National Birth Cohort.
AB  - BACKGROUND: Previous studies have investigated physical and psychosocial job
      exposures separately in relation to foetal growth. We therefore investigated if
      occupational lifting and psychosocial job strain interact to affect foetal growth
      and gestational length. We hypothesised that heavy lifting and high job strain
      would increase the risk of impacted foetal growth (small or large for gestational
      age) and preterm birth. METHODS: The cohort included 47,582 pregnancies from the
      Danish National Birth Cohort (1996-2002), where the woman was pregnant at 22
      gestational weeks (GW), expected one child and worked >=30 hours/week.
      Information on occupational lifting and psychosocial job strain was derived from
      an interview (16+/-3.0 GW). Data to calculate small and large for gestational age
      (SGA/LGA) and gestational length was retrieved from the Medical Birth Register.
      Interaction between lifting and job strain (Karasek's model) was analysed by
      multinomial logistic regression. RESULTS: Overall, the adjusted regression
      analysis showed statistically significant interaction between lifting and job
      strain for SGA and LGA. For each additional 250 kg lifted/day, high strain women
      (high Demand/low Control) had increased odds of giving birth to a LGA-child (OR =
      1.15; 95% CI 1.06-1.26), whereas women in the active group (high Demand/high
      Control) had increased odds of giving birth to a SGA child (OR = 1.12; 95% CI
      1.03-1.23). When women lifting <=1000 kg/day were excluded in the sensitivity
      analyses the interaction between lifting and job strain became insignificant. No
      interaction of lifting and job strain was found for gestational length.
      CONCLUSIONS: The main findings may give some support to our hypothesis, as
      lifting in combination high with job strain increased the risk of giving birth to
      a LGA child. This finding was, however, not supported in the sensitivity analysis
      and no association of the interaction was found relative to gestational length.

PMID- 30231021
TI  - Balancing selection on a recessive lethal deletion with pleiotropic effects on
      two neighboring genes in the porcine genome.
AB  - Livestock populations can be used to study recessive defects caused by
      deleterious alleles. The frequency of deleterious alleles including recessive
      lethal alleles can stay at high or moderate frequency within a population,
      especially if recessive lethal alleles exhibit an advantage for favourable traits
      in heterozygotes. In this study, we report such a recessive lethal deletion of
      212kb (del) within the BBS9 gene in a breeding population of pigs. The deletion
      produces a truncated BBS9 protein expected to cause a complete loss-of-function,
      and we find a reduction of approximately 20% on the total number of piglets born
      from carrier by carrier matings. Homozygous del/del animals die mid- to late
      gestation, as observed from high increase in numbers of mummified piglets
      resulting from carrier-by-carrier crosses. The moderate 10.8% carrier frequency
      (5.4% allele frequency) in this pig population suggests an advantage on a
      favourable trait in heterozygotes. Indeed, heterozygous carriers exhibit
      increased growth rate, an important selection trait in pig breeding. Increased
      growth and appetite together with a lower birth weight for carriers of the BBS9
      null allele in pigs is analogous to the phenotype described in human and mouse
      for (naturally occurring) BBS9 null-mutants. We show that fetal death, however,
      is induced by reduced expression of the downstream BMPER gene, an essential gene
      for normal foetal development. In conclusion, this study describes a lethal 212kb
      deletion with pleiotropic effects on two different genes, one resulting in fetal
      death in homozygous state (BMPER), and the other increasing growth (BBS9) in
      heterozygous state. We provide strong evidence for balancing selection resulting
      in an unexpected high frequency of a lethal allele in the population. This study
      shows that the large amounts of genomic and phenotypic data routinely generated
      in modern commercial breeding programs deliver a powerful tool to monitor and
      control lethal alleles much more efficiently.

PMID- 30231022
TI  - Forecasting the global demand for HIV monitoring and diagnostic tests: A 2016
      2021 analysis.
AB  - INTRODUCTION: Despite considerable progress, just over half of the 37 million
      people eligible to start antiretroviral therapy (ART) have accessed treatment and
      millions of HIV-positive people still do not know their status. With demand for
      ART continuing to grow, meeting the ambitious 90-90-90 HIV treatment targets will
      depend on improved access to high-quality diagnostics to both diagnose infection
      and monitor treatment adherence in low and middle-income countries (LMICs).
      Robust projections of future demand for CD4, viral load (VL), HIV early-infant
      diagnosis (EID) tests and HIV rapid diagnostic tests (RDTs) are needed as scale
      up continues. METHODS: We estimate the current coverage for HIV diagnostics and
      project future demand to 2021 using a consolidated forecast using data on past
      coverage and current demand from a number of sources, from 130 predominantly LMIC
      countries. RESULTS: We forecast that the overall number of CD4 tests is expected
      to decline between now and 2021 as more countries adopt test-and-treat and shift
      to VL testing for patient monitoring. Our consolidated forecast projects a
      gradual decline in demand for CD4 tests to 16.6 million by 2021. We anticipate
      that demand for VL tests will increase to 28.5 million by 2021, reflecting the
      increasing number of people who will receive ART and the adoption of VL testing
      for patient monitoring. We expect that the demand for EID tests will grow more
      rapidly than in past years, driven by the implementation of testing at birth in
      programmes globally, in line with WHO guideline recommendations, doubling to 2.1
      million tests by 2021. Demand for rapid diagnostic tests is also likely to
      increase, reaching 509 million tests by 2021. DISCUSSION: In order to achieve the
      ambitious 90-90-90 targets, it will be essential to maintain and improve access
      to CD4, VL, EID tests and RDTs. These projections provide insight into the global
      demand we can expect to see for these HIV monitoring and diagnostic tests, both
      in relation to historical trends, and the 90-90-90 targets. Our projections will
      better enable producers to ensure adequate supply, and to support procurement
      organisations in planning future funding and purchase plans to meet the
      anticipated demand. The findings highlight the ongoing need for governments and
      international funding bodies to prioritise improving capacity and access to HIV
      diagnostic and monitoring technologies in line with demand.

PMID- 30231023
TI  - Heavy metal sensitivities of gene deletion strains for ITT1 and RPS1A connect
      their activities to the expression of URE2, a key gene involved in metal
      detoxification in yeast.
AB  - Heavy metal and metalloid contaminations are among the most concerning types of
      pollutant in the environment. Consequently, it is important to investigate the
      molecular mechanisms of cellular responses and detoxification pathways for these
      compounds in living organisms. To date, a number of genes have been linked to the
      detoxification process. The expression of these genes can be controlled at both
      transcriptional and translational levels. In baker's yeast, Saccharomyces
      cerevisiae, resistance to a wide range of toxic metals is regulated by
      glutathione S-transferases. Yeast URE2 encodes for a protein that has glutathione
      peroxidase activity and is homologous to mammalian glutathione S-transferases.
      The URE2 expression is critical to cell survival under heavy metal stress. Here,
      we report on the finding of two genes, ITT1, an inhibitor of translation
      termination, and RPS1A, a small ribosomal protein, that when deleted yeast cells
      exhibit similar metal sensitivity phenotypes to gene deletion strain for URE2.
      Neither of these genes were previously linked to metal toxicity. Our gene
      expression analysis illustrates that these two genes affect URE2 mRNA expression
      at the level of translation.

PMID- 30231024
TI  - Community delivery of antiretroviral drugs: A non-inferiority cluster-randomized
      pragmatic trial in Dar es Salaam, Tanzania.
AB  - BACKGROUND: With the increase in people living with HIV in sub-Saharan Africa and
      expanding eligibility criteria for antiretroviral therapy (ART), there is intense
      interest in the use of novel delivery models that allow understaffed health
      systems to successfully deal with an increasing demand for antiretroviral drugs
      (ARVs). This pragmatic randomized controlled trial in Dar es Salaam, Tanzania,
      evaluated a novel model of ARV community delivery: lay health workers (home-based
      carers [HBCs]) deliver ARVs to the homes of patients who are clinically stable on
      ART, while nurses and physicians deliver standard facility-based care for
      patients who are clinically unstable. Specifically, the trial aimed to assess
      whether the ARV community delivery model performed at least equally well in
      averting virological failure as the standard of care (facility-based care for all
      ART patients). METHODS AND FINDINGS: The study took place from March 1, 2016, to
      October 27, 2017. All (48) healthcare facilities in Dar es Salaam that provided
      ART and had an affiliated team of public-sector HBCs were randomized 1:1 to
      either (i) ARV community delivery (intervention) or (ii) the standard of care
      (control). Our prespecified primary endpoint was the proportion of adult non
      pregnant ART patients with virological failure at the end of the study period.
      The prespecified margin of non-inferiority was a risk ratio (RR) of 1.45. The
      mean follow-up period was 326 days. We obtained intent-to-treat (ITT) RRs using a
      log-binomial model adjusting standard errors for clustering at the level of the
      healthcare facility. A total of 2,172 patients were enrolled at intervention
      (1,163 patients) and control (1,009 patients) facilities. Of the 1,163 patients
      in the intervention arm, 516 (44.4%) were both clinically stable on ART and opted
      to receive ARVs in their homes or at another meeting point of their choosing in
      the community. At the end of the study period, 10.9% (95/872) of patients in the
      control arm and 9.7% (91/943) in the intervention arm were failing virologically.
      The ITT RR for virological failure demonstrated non-inferiority of the ARV
      community delivery model (RR 0.89 [1-sided 95% CI 0.00-1.18]). We observed no
      significant difference between study arms in self-reported patient healthcare
      expenditures over the last 6 months before study exit. Of those who received ARVs
      in the community, 97.2% (95% CI 94.7%-98.7%) reported being either "satisfied" or
      "very satisfied" with the program. Other than loss to follow-up (18.9% in the
      intervention and 13.6% in the control arm), the main limitation of this trial was
      that substantial decongestion of healthcare facilities was not achieved, thus
      making the logic for our preregistered ITT approach (which includes those
      ineligible to receive ARVs at home in the intervention sample) less compelling.
      CONCLUSIONS: In this study, an ARV community delivery model performed at least as
      well as the standard of care regarding the critical health indicator of
      virological failure. The intervention did not significantly reduce patient
      healthcare expenditures, but satisfaction with the program was high and it is
      likely to save patients time. Policy-makers should consider piloting, evaluating,
      and scaling more ambitious ARV community delivery programs that can reach higher
      proportions of ART patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02711293.

PMID- 30231025
TI  - Karnatukul (Serpent's Glen): A new chronology for the oldest site in Australia's
      Western Desert.
AB  - The re-excavation of Karnatukul (Serpent's Glen) has provided evidence for the
      human occupation of the Australian Western Desert to before 47,830 cal. BP
      (modelled median age). This new sequence is 20,000 years older than the previous
      known age for occupation at this site. Re-excavation of Karnatukul aimed to
      contextualise the site's painted art assemblage. We report on analyses of
      assemblages of stone artefacts and pigment art, pigment fragments, anthracology,
      new radiocarbon dates and detailed sediment analyses. Combined these add
      significantly to our understanding of this earliest occupation of Australia's
      Western Desert. The large lithic assemblage of over 25,000 artefacts includes a
      symmetrical geometric backed artefact dated to 45,570-41,650 cal. BP. The
      assemblage includes other evidence for hafting technology in its earliest phase
      of occupation. This research recalibrates the earliest Pleistocene occupation of
      Australia's desert core and confirms that people remained in this part of the
      arid zone during the Last Glacial Maximum. Changes in occupation intensity are
      demonstrated throughout the sequence: at the late Pleistocene/Holocene
      transition, the mid-Holocene and then during the last millennium. Karnatukul
      documents intensive site use with a range of occupation activities and different
      signalling behaviours during the last 1,000 years. This correlation of rock art
      and occupation evidence refines our understanding of how Western Desert peoples
      have inscribed their landscapes in the recent past, while the newly described
      occupation sequence highlights the dynamic adaptive culture of the first
      Australians, supporting arguments for their rapid very early migration from the
      coasts and northern tropics throughout the arid interior of the continent.

PMID- 30231026
TI  - New polybranchiaspiform fishes (Agnatha: Galeaspida) from the Middle Palaeozoic
      of China and their ecomorphological implications.
AB  - The 438-370-million-year-old galeaspids, diversified armoured jawless vertebrates
      ('ostracoderms') from China and northern Vietnam, were assumed to have a benthic
      feeding habit in a coastal, marine environment. Here, we describe two new genera
      of galeaspid fishes, Platylomaspis gen. nov. and Nanningaspis gen. nov. from the
      Middle Palaeozoic of China. The two new forms are characterized by a rostral
      process and strikingly broad ventral rim, and clustered with Gumuaspis to form a
      new family, Gumuaspidae, which represents the most primitive clade of
      Polybranchiaspiformes. They extend the earliest occurrence of
      Polybranchiaspiformes backward about 19 million years, and expand its
      geographical distribution from southern China and northern Vietnam to the Tarim
      Basin, northwestern China. The new taxa exhibit many morphological convergences
      with modern rays, and might specify a new kind of lifestyle of galeaspids, the
      half burrowing habit. Probably benefiting from the new lifestyle, the Gumuaspidae
      has become the longest lasting galeaspid family. The new findings demonstrated
      that the demersal galeaspids had developed three different kinds of lifestyles:
      semi-infaunal benthic (half buried), epibenthic, and suprabenthic (nektonic)
      habits to accommodate to differentiated ecological niches, and reached the peak
      of their diversity by the Pragian of the Early Devonian.

PMID- 30231027
TI  - Perspective of elderly patients on chronic use of potentially inappropriate
      medication - Results of the qualitative CIM-TRIAD study.
AB  - Although potentially inappropriate medication (PIM) is associated with risk of
      harm due to adverse effects, it is frequently prescribed for elderly patients.
      The aim of this qualitative multi-center study was to gain insight into
      contextual factors that might lead to chronic PIM use. We conducted semi
      structured interviews with elderly patients with or without chronic PIM use
      (patient interviews: n = 52). Patients were between 86 and 96 years old. The
      participants were recruited from the AgeCoDe study. Interviews were audiotaped
      and transcribed verbatim. The transcripts of the interviews were analysed using
      qualitative content analysis. Deductive and inductive categories were determined.
      We found contextual factors related to the patient and related to patient-general
      practitioner (GP) communication that might lead to chronic PIM use (i.e.,
      positive features of PIM, maintaining characteristics of medication intake,
      barriers to deprescribe PIM, external actors supporting PIM intake, system
      related factors). Besides certain health-related behaviours (e.g., own obligation
      to report to GP) and medication-related attitudes and knowledge (e.g., awareness
      of side effects and interaction of medicines), patient-GP-interactions that were
      characterised by mutual agreements on drugs (e.g., concerning dosage or
      discontinuation of a drug) might be advantageous to reduce the probability of
      chronic PIM use. The results might assist in the development of guidelines and
      educational programs aiming to reduce PIM use in the elderly.

PMID- 30231028
TI  - Discovery of microRNA-like RNAs during early fruiting body development in the
      model mushroom Coprinopsis cinerea.
AB  - Coprinopsis cinerea is a model mushroom particularly suited for the study of
      fungal fruiting body development and the evolution of multicellularity in fungi.
      While microRNAs (miRNAs) have been extensively studied in animals and plants for
      their essential roles in post-transcriptional regulation of gene expression,
      miRNAs in fungi are less well characterized and their potential roles in
      controlling mushroom development remain unknown. To identify miRNA-like RNAs
      (milRNAs) in C. cinerea and explore their expression patterns during the early
      developmental transition of mushroom development, small RNA libraries of
      vegetative mycelium and primordium were generated and putative milRNA candidates
      were identified following the standards of miRNA prediction in animals and
      plants. Two out of 22 novel predicted milRNAs, cci-milR-12c and cci-milR-13e-5p,
      were validated by northern blot and stem-loop reverse transcription real-time
      PCR. Cci-milR-12c was differentially expressed whereas the expression levels of
      cci-milR-13e-5p were similar in the two developmental stages. Target prediction
      of the validated milRNAs resulted in genes associated with fruiting body
      development, including pheromone, hydrophobin, cytochrome P450, and protein
      kinase. Essential genes for miRNA biogenesis, including three coding for Dicer
      like (DCL), one for Argonaute (AGO), one for AGO-like and one for quelling
      deficient-2 (QDE-2) proteins, were also identified in the C. cinerea genome.
      Phylogenetic analysis showed that the DCL and AGO proteins of C. cinerea were
      more closely related to those in other basidiomycetes and ascomycetes than to
      those in animals and plants. Taken together, our findings provided the first
      evidence for milRNAs in the model mushroom and their potential roles in
      regulating fruiting body development. New information on the evolutionary
      relationship of milRNA biogenesis proteins across kingdoms has also provided new
      insights for guiding further functional and evolutionary studies of miRNAs.

PMID- 30231029
TI  - Improved methods to capture the total societal benefits of zoonotic disease
      control: Demonstrating the cost-effectiveness of an integrated control programme
      for Taenia solium, soil transmitted helminths and classical swine fever in
      northern Lao PDR.
AB  - BACKGROUND: Control and elimination of zoonotic diseases requires robust
      information about their effect on both human and livestock health in order to
      enable policy formulation and the allocation of resources. This study aimed to
      evaluate the cost-effectiveness of controlling Taenia solium
      taeniasis/cysticercosis in both humans and pigs, and soil-transmitted helminths
      (STH) in humans by integrating their control to on-going human and animal health
      control programmes in northern Lao People's Democratic Republic. METHOD: A cross
      sectional study was carried out in 49 households, focusing on the prevalence of
      T. solium taenias/cysticercosis and soil transmitted helminths before and after a
      twelve month intervention. The village data was collected using a semi-structured
      questionnaire through a door-to-door survey. The village data was then projected
      to the wider northern Lao PDR population using stochastic modelling and cost
      effectiveness ratio (after aggregating the net cost to capture both human and
      animal health parameters) and GDP per capita as a threshold, to determine the
      cost-effectiveness of the integrated control of T. solium taeniasis/
      cysticercosis and STH, assuming linear scaling out of the intervention. The
      zoonotic DALY (zDALY) approach was also used as an alternative method of
      estimating the cost-effectiveness ratio of controlling T. solium
      taeniasis/cysticercosis in humans and pigs. FINDINGS: Using cost-effectiveness
      analysis after aggregating the net cost and control of T. solium
      taeniasis/cysticercosis alone as the base case, the study found that simultaneous
      control of T. solium taeniasis/cysticercosis in humans and pigs, STH in humans
      and Classical Swine Fever (CSF) in pigs was USD 14 per DALY averted and USD 234
      per zDALY averted using zDALY method hence considered highly cost-effective
      whereas controlling T. solium taeniasis/cysticercosis without incorporating STH
      and CSF was the least cost-effective (USD 3,672 per DALY averted). Additionally,
      the cost-effectiveness of controlling T. solium taeniasis/cysticercosis in people
      and pigs using zDALY as an alternative method was USD 3,662 per zDALY averted
      which was quite close to our findings using the aggregate net cost method.
      CONCLUSION: The study showed that control of T. solium taeniasis/cysticercosis
      alone in humans and pigs is not cost-effective in northern Lao PDR whereas
      control of STH is. Consequently, integrating T. solium taeniasis/cysticercosis
      control with other cost-effective programmes such as STH and CSF markedly
      improved the cost-effectiveness of the intervention. This is especially important
      in low resource countries where control of zoonotic neglected tropical diseases
      could be integrated with the human and animal health sectors to optimize use of
      the limited resources. TRIAL REGISTRATION: Australia New Zealand Clinical Trials
      Registry (ANZCTR) ACTRN12614001067662.

PMID- 30231030
TI  - Progress toward UNAIDS 90-90-90 targets: A respondent-driven survey among female
      sex workers in Kampala, Uganda.
AB  - BACKGROUND: We investigated progress towards UNAIDS 90-90-90 targets among female
      sex workers in Kampala, Uganda, who bear a disproportionate burden of HIV.
      METHODS: Between April and December 2012, 1,487 female sex workers, defined as
      women, 15-49 years, residing in greater Kampala, and selling sex for money in the
      last 6 months, were recruited using respondent-driven sampling. Venous blood was
      collected for HIV and viral load testing [viral load suppression (VLS) defined as
      <1,000 copies/mL]. We collected data using audio computer-assisted self
      interviews and calculated weighted population-level estimates. RESULTS: The
      median age was 27 years (interquartile range: 23 to 32). HIV seroprevalence was
      31.4% (95% confidence interval [CI]: 29.0, 33.7%). Among all female sex workers
      who tested HIV-positive in the survey (population-level targets), 45.5% (95% CI:
      40.1, 51.0) had knowledge of their serostatus (population-level target: 90%),
      37.8% (95% CI: 32.2, 42.8) self-reported to be on ART (population-level target:
      81%), and 35.2% (95% CI: 20.7, 30.4) were virally suppressed (population-level
      target: 73%). CONCLUSIONS: HIV prevalence among Kampala female sex workers is
      high, whereas serostatus knowledge and VLS are far below UNAIDS targets. Kampala
      female sex workers are in need of intensified and targeted HIV prevention and
      control efforts.

PMID- 30231032
TI  - A novel mathematical method for disclosing oscillations in gene transcription: A
      comparative study.
AB  - : Circadian rhythmicity, the 24-hour cycle responsive to light and dark, is
      determined by periodic oscillations in gene transcription. This phenomenon has
      broad ramifications in physiologic function. Recent work has disclosed more
      cycles in gene transcription, and to the uncovering of these we apply a novel
      signal processing methodology known as the pencil method and compare it to
      conventional parametric, nonparametric, and statistical methods. METHODS: In
      order to assess periodicity of gene expression over time, we analyzed a database
      derived from livers of mice entrained to a 12-hour light/12-hour dark cycle. We
      also analyzed artificially generated signals to identify differences between the
      pencil decomposition and other alternative methods. RESULTS: The pencil
      decomposition revealed hitherto-unsuspected oscillations in gene transcription
      with 12-hour periodicity. The pencil method was robust in detecting the 24-hour
      circadian cycle that was known to exist, as well as confirming the existence of
      shorter-period oscillations. A key consequence of this approach is that
      orthogonality of the different oscillatory components can be demonstrated. thus
      indicating a biological independence of these oscillations, that has been
      subsequently confirmed empirically by knocking out the gene responsible for the
      24-hour clock. CONCLUSION: System identification techniques can be applied to
      biological systems and can uncover important characteristics that may elude
      visual inspection of the data. SIGNIFICANCE: The pencil method provides new
      insights on the essence of gene expression and discloses a wide variety of
      oscillations in addition to the well-studied circadian pattern. This insight
      opens the door to the study of novel mechanisms by which oscillatory gene
      expression signals exert their regulatory effect on cells to influence human
      diseases.

PMID- 30231031
TI  - Influence of natural variation in berry size on the volatile profiles of Vitis
      vinifera L. cv. Merlot and Cabernet Gernischt grapes.
AB  - This study was conducted during the 2014 and 2015 vintages on Vitis vinifera L.
      cv. Merlot and Cabernet Gernischt to investigate whether natural variation in
      berry size could affect grape aromatic compounds. Grape berries were separated
      into three size categories based on their diameter: small, middle and large. The
      results showed that berry size exerted a significant influence on the volatile
      profiles of both winegrape varieties. Hierarchical clustering analysis
      demonstrated that the volatile profiles of middle berries were different from
      those of large and small berries. Middle berries had the greatest abundance of
      aroma compounds, followed by small and large berries. Especially, C6/C9
      compounds, norisoprenoids, terpenoids showed markedly different concentrations
      among differently sized Merlot berries and C6/C9 compounds, terpenoids among
      differently sized Cabernet Gernischt berries. Middle berries of both grape
      varieties may possess the greatest intensity of fresh-green, fruity and floral
      aromas due to the high odour activity values (OAVs) of decanal, hexanal, (E)-2
      hexenal, (E)-beta-damascenone and beta-ionone in middle sizes of Merlot berries
      and the high OAVs of (E)-2-hexenal and (E)-beta-damascenone in middle sizes of
      Cabernet Gernischt berries. This knowledge could be important for winemakers to
      conduct targeted berry sorting, thereby improving the aromatic quality of grapes.

PMID- 30230889
TI  - Observation of the chi_{b1}(3P) and chi_{b2}(3P) and Measurement of their Masses.
AB  - The chi_{b1}(3P) and chi_{b2}(3P) states are observed through their
      Upsilon(3S)gamma decays, using an event sample of proton-proton collisions
      collected by the CMS experiment at the CERN LHC. The data were collected at a
      center-of-mass energy of 13 TeV and correspond to an integrated luminosity of
      80.0  fb^{-1}. The Upsilon(3S) mesons are identified through their dimuon decay
      channel, while the low-energy photons are detected after converting to e^{+}e^{-}
      pairs in the silicon tracker, leading to a chi_{b}(3P) mass resolution of 2.2
      MeV. This is the first time that the J=1 and 2 states are well resolved and their
      masses individually measured: 10513.42+/-0.41(stat)+/-0.18(syst)  MeV and
      10524.02+/-0.57(stat)+/-0.18(syst)  MeV; they are determined with respect to the
      world-average value of the Upsilon(3S) mass, which has an uncertainty of 0.5 MeV.
      The mass splitting is measured to be 10.60+/-0.64(stat)+/-0.17(syst)  MeV.

PMID- 30231033
TI  - The relationship between nursing home quality and costs: Evidence from the VA.
AB  - Ensuring quality of care in nursing homes is a public health priority, yet how
      nursing home quality relates to cost is not well understood. This paper addresses
      this relationship for 132 VA community living centers (nursing homes), for fiscal
      years 2014 and 2015. We estimated cost models using the VA Decision Support
      System which tracks total direct costs and nursing direct costs for individual
      resident segments of care. We summed residents' total costs and nursing costs to
      the community living center level for each year. Annual facility costs then were
      regressed on quality of care measured with composite scores based on 13 distinct
      adverse events. Results indicated that higher quality was associated with higher
      predicted cost. However, we did not find evidence that higher costs were driven
      by high nurse staffing levels.

PMID- 30231034
TI  - Easy and efficient production of completely embryonic-stem-cell-derived mice
      using a micro-aggregation device.
AB  - There is an increasing demand for genetically modified mice produced without
      crossing, for rapid phenotypic screening studies at the organismal level. For
      this purpose, generation of completely embryonic-stem-cell (ESC)-derived chimeric
      mice without crossing is now possible using a microinjection or aggregation
      method with 3i culture medium. However, the microinjection of ESCs into
      blastocyst, morula, or 8-cell-stage embryos requires a highly skilled operator.
      The aggregation method is an easier alternative, but the conventional aggregation
      protocol still requires special skills. To make the aggregation method easier and
      more precise, here we developed a micro-aggregation device. Unlike conventional 3
      dimensional culture, which uses hanging-drop devices for aggregation, we
      fabricated a polystyrene funnel-like structure to smoothly drop ESCs into a small
      area (300-MUm in diameter) at the bottom of the device. The bottom area was
      designed so that the surface tension of the liquid-air interface prevents the
      cells from falling. After aggregation, the cells can be recovered by simply
      exerting pressure on the liquid from the top. The microdevice can be set upon a
      regular 96-well plate, so it is compatible with multichannel pipette use or
      machine operation. Using the microdevice, we successfully obtained chimeric
      blastocysts, which when transplanted resulted in completely ESC-derived chimeric
      mice with high efficiency. By changing the number of ESCs in the aggregate, we
      found that the optimum number of co-cultured ESCs was around 90~120 per embryo.
      Under this condition, the efficiency of generating completely ESC-derived mice
      was the same or better than that of the injection method. These results indicated
      that our microdevice can be used to produce completely ESC-derived chimeric mice
      easily and with a high success rate, and thus represents a promising alternative
      to the conventional microinjection or aggregation method, especially for high
      throughput, parallel experimental applications.

PMID- 30231035
TI  - Use of scientific evidence by dentists in Brazil: Room for improving the evidence
      based practice.
AB  - This study investigated the use of scientific evidence and the practice of
      evidence-based dentistry (EBD) among dentists working in Brazil. An online
      questionnaire was emailed to dentists registered with Brazilian state dental
      councils. The questionnaire assessed the demographic, educational, and work
      characteristics of the sample, along with habits in reading scientific articles
      and other updating resources. Data were analyzed descriptively and by using
      Bonferroni, Kruskal-Wallis, ANOVA, and T-test statistical methods (alpha = 0.05).
      A total of 795 responses were received between June, 2015 and January, 2016. The
      response rate was not calculated because it was not possible to determine
      precisely how many dentists received these e-mails. Over 77% of the responding
      dentists completed postgraduate training. They referred mainly to books,
      scientific or clinical journals, conferences, and short-term courses for updating
      their knowledge. Dentists who reported having a habit of reading scientific
      journals (60.9%) showed a preference for reading case reports, clinical research
      articles, and literature reviews. Most dentists (77.5%) reported changing their
      clinical behaviors or procedures based on information gleaned from journal
      articles. The types of articles that led them to change their clinical practices
      were primarily clinical research articles and case reports. Working in the public
      sector was also associated with a lower prevalence of a habit of reading
      scientific journals and practicing EBD (i.e., self-reported practice). The
      results suggest that dentists are interested in reading journal articles,
      especially those addressing clinical outcomes, and that there is room for
      improving the practice of EBD, particularly in the public sector.

PMID- 30231036
TI  - The Dark Triad and framing effects predict selfish behavior in a one-shot
      Prisoner's Dilemma.
AB  - What causes us to display selfish behaviors? We explored the extent to which Dark
      Triad traits (sub-clinical psychopathy, narcissism, and Machiavellianism) support
      a selfish behavioral strategy. We related performance on a hypothetical
      Prisoner's Dilemma (an economic game that simulates a two-person social dilemma)
      to participants' (N = 1400) Dark Triad scores. Because contextual factors also
      impact selfish behaviors, we tested how framing (gain vs. loss; and social vs.
      nonsocial) shaped performance in the Prisoner's Dilemma. Participants with high
      Dark Triad scores were more likely to behave selfishly in the Prisoner's Dilemma.
      Participants were also most likely to betray their partner in loss-framed and non
      socially framed contexts. These effects did not interact with Dark Triad scores.
      Our data are consistent with the view that seemingly negative personality traits
      (like those associated with the Dark Triad traits) that persist in the population
      may serve as evolutionarily adaptive behavioral strategies.

PMID- 30231040
TI  - Perspectives on using decision-making nudges in physician-patient communications.
AB  - Patients engaging in shared decision making must weigh the likelihood of positive
      and negative outcomes and deal with uncertainty and negative emotions in the
      situations where desirable options might not be available. The use of "nudges,"
      or communication techniques that influence patients' choices in a predictable
      direction, may assist patients in making complex decisions. However, nudging
      patients may be perceived as inappropriate influence on patients' choices. We
      sought to determine whether key stakeholders, physicians, and laypersons without
      clinical training consider the use of nudges to be ethical and appropriate in
      medical decision making. Eighty-nine resident-physicians and 336 Mechanical-Turk
      workers (i.e., non-clinicians) evaluated two hypothetical preference-sensitive
      situations, in which a patient with advanced cancer chooses between chemotherapy
      and hospice care. We varied the following: (1) whether or not the patient's
      decision was influenced by a mistaken judgment (i.e., decision-making bias) and
      (2) whether or not the physician used a nudge. Each participant reported the
      extent to which the communication was ethical, appropriate, and desirable. Both
      physicians and non-clinicians considered using nudges more positively than not
      using them, regardless of an initial decision-making bias in patients'
      considerations. Decomposing this effect, we found that physicians viewed the
      nudge that endorsed hospice care more favorably than the nudge that endorsed
      chemotherapy, while non-clinicians viewed the nudge that endorsed chemotherapy
      more favorably than the nudge that endorsed hospice care. We discuss implications
      and propose exploring further physicians' and patients' differences in the
      perception of nudges; the differences may suggest limitations for using nudges in
      medical decisions.

PMID- 30231038
TI  - Optimization of an ecological integrity monitoring program for protected areas:
      Case study for a network of national parks.
AB  - Over the last few years, several of the world's national park networks have
      implemented ecological integrity monitoring programs. These programs are based on
      a series of indicators to detect changes in ecosystem integrity. There are many
      scientific and logistical challenges in developing these programs due to limits
      in both our knowledge of ecosystems functioning and the resources for
      implementing such programs. Thus, the relatively quick and simple implementation
      of many monitoring programs has been to the detriment of their scientific
      validity. Few studies have focused on evaluating an entire monitoring program.
      This project presents an approach to evaluate the ecological and statistical
      relevance of ecosystem integrity indicators measured within a program with the
      goal of iterative optimization. The approach is based on three complementary
      elements: (1) spatial characterization of park ecosystems based on the
      classification of satellite imagery, (2) ecological validation of indicators
      based on ecosystem conceptual models and (3) statistical validation of indicators
      based on analyses of statistical power. This innovative approach allows a
      systematic, quantified, reproducible and generalizable review of the indicators
      of an ecological integrity monitoring program. It provides managers with an
      overview of the spatial representativeness of indicators, their ecological and
      statistical relevance according to different parameters such as the period
      monitored, the amount of change to be detected, and the degree of significance.
      Thus, the approach identifies monitoring gaps and offers various alternatives for
      improving sampling. The approach was developed and tested in the network of
      Quebec national parks, more specifically in the Frontenac, Jacques-Cartier and
      Bic national parks. The results clearly identify the strengths and weaknesses of
      the current program in place and possible improvements are proposed for these
      parks. This approach is a relevant tool for park networks, particularly for those
      that have limited resources for monitoring ecological integrity.

PMID- 30231039
TI  - 'Love at first sight': The effect of personality and colouration patterns in the
      reproductive success of zebrafish (Danio rerio).
AB  - Individual differences in animal personality and external appearance such as
      colouration patterns have both been extensively studied separately. A significant
      body of research has explored many of pertinent ecological and biological aspects
      that can be affected by them and their impact upon fitness. Currently little is
      known about how both factors interact and their effect on reproductive success.
      In this study, we evaluated two major parameters contributing to the fitness of
      the species: reproduction and offspring survival. We selected two different
      phenotypes of the zebrafish (Danio rerio) selected by their colouration patterns:
      phenotype 1) named Wild type, UAB line (WT-UAB) with a homogeneous colouration
      pattern (clear and defined lateral stripes) and phenotype 2) Wild type indefinite
      (WT-I) had a heterogeneous colouration pattern and different degrees of lateral
      stripe definition. All animals were also screened for personality. We then
      compared their reproductive success (spawning rate) and offspring survival at
      different stages, from egg to larvae, and for 2 successive generations (parental
      generation was G0; First and second generations were G1 and G2 respectively). Our
      results show that personality traits were the main source of variability between
      the fitness components measured: both personalities had similar total numbers of
      eggs spawned but proactive animals, for both colour phenotypes, had higher
      reproductive success. This was reflected in a higher percentage of spawning
      viability at 1day post fertilization (dpf), higher total survival and growth
      rates at larval stages. Proactive phenotypes from WT-UAB population had a higher
      overall fitness in comparison to the other phenotypes studied. Our findings imply
      that fitness of this species when kept under similar husbandry conditions is
      significantly influenced by parental personality and not by their external
      appearance. Under these conditions the reproductive success is enhanced. The
      implications of this study are important for zebrafish breeding and husbandry in
      captivity and are relevant toward understanding the underlying drivers of trait
      selection in natural environments.

PMID- 30231037
TI  - Acute muscle fatigue and CPR quality assisted by visual feedback devices: A
      randomized-crossover simulation trial.
AB  - OBJECTIVE: To analyse the acute muscular fatigue (AMF) in triceps brachii and
      rectus abdominis during compression-only and standard cardiopulmonary
      resuscitation (CPR) performed by certified basic life support providers. METHODS:
      Twenty-six subjects were initially recruited and randomly allocated to two study
      groups according to the muscles analysed; eighteen finally met the inclusion
      criteria (nine in each group). Both groups carried out two CPR tests (compression
      only and standard CPR) of 10 min divided into five 2-min intermittent periods.
      The ventilation method was freely chosen by each participant (mouth-to-mouth,
      pocket-mask or bag-valve-mask). CPR feedback was provided all the time. AMF was
      measured by tensiomyography at baseline and after each 2-min period of the CPR
      test, in triceps brachii or rectus abdominis according to the study group.
      RESULTS: Rectus abdominis' contraction time increased significantly during the
      fifth CPR period (p = 0.020). Triceps brachii's radial muscle belly displacement
      (p = 0.047) and contraction velocity (p = 0.018) were lower during compression
      only CPR than during standard CPR. Participants who had trained previously with
      feedback devices achieved better CPR quality results in both protocols. Half of
      participants chose bag-valve-mask to perform ventilations but attained lower
      significant ventilation quality than the other subjects. CONCLUSIONS: Compression
      only CPR induces higher AMF than standard CPR. Significantly higher fatigue
      levels were found during the fifth CPR test period, regardless of the method.
      Adequate rescuer's strength seems to be a requisite to take advantage of CPR
      quality feedback devices. Training should put more emphasis on the quality of
      ventilation during CPR.

PMID- 30231041
TI  - Is nonalcoholic fatty liver disease associated with the development of prostate
      cancer? A nationwide study with 10,516,985 Korean men.
AB  - BACKGROUND: Growing evidence supports that prostate cancer (PCa) is a metabolic
      syndrome-related cancer, but the evidence is lacking regarding the association
      between nonalcoholic fatty liver disease (NAFLD) and PCa. We aimed to investigate
      whether PCa is related with NAFLD in Korean adults. METHODS: Data from the
      National Health Insurance Corporation between 2009 and 2012 were analyzed using
      multivariate logistic regression method. NALFD was defined based on the fatty
      liver index (FLI) and hepatic steatosis index (HSI). Newly diagnosed PCa was
      identified using the claims data. RESULTS: NAFLD based on FLI and HSI was
      identified in 2,002,375 (19%) and 2,629,858 (25%) of 10,516,985 subjects,
      respectively. Each FLI >= 60 and HSI >= 36 was independently associated with the
      development of PCa after adjusting for other confounders (hazard ratio (HR) 1.09,
      95% CI: 1.06-1.12 and HR 1.19, 95% CI: 1.16-1.23). The association was more
      prominent among those who were older (FLI, >= 65 years old and HSI, >= 40 years
      old), were not currently smoking, were presently consuming alcohol (< 30g/day)
      and had null components of metabolic syndrome than each counterpart. Non-obese
      persons with NAFLD defined by HSI had a higher risk of developing PCa than those
      with body mass index > 25 Kg/m2. CONCLUSIONS: NAFLD defined by FLI or HSI may
      help identify high-risk individuals for developing PCa particular in the elderly,
      even in the absence of obesity or metabolic syndrome. Future studies on this
      topic should necessarily be repeated based on ultrasonographic findings.

PMID- 30231044
TI  - Scientific impact increases when researchers publish in open access and
      international collaboration: A bibliometric analysis on poverty-related disease
      papers.
AB  - BACKGROUND: The European & Developing Countries Clinical Trials Partnership
      (EDCTP), like many other research funders, requires its grantees to make papers
      available via open access (OA). This article investigates the effect of
      publishing in OA journals and international collaboration within and between
      European and sub-Saharan African countries on citation impact and likelihood of
      falling into the top 1% and top 10% most cited papers in poverty-related disease
      (PRD) research. METHODS: Disease-specific research publications were identified
      in the Web of ScienceTM and MEDLINE using Medical Subject Heading (MeSH) terms.
      Data on the open accessibility of scientific literature were derived from
      1science oaFindr. Publication data, including relative citation counts, were
      extracted for 2003-2015. Regression models were applied to quantify the
      relationship between relative citations and presence in the 1% and top 10% most
      cited papers versus OA and international collaboration. RESULTS: The results show
      that since 2003 papers on PRDs have become increasingly available in OA. Among
      all PRD areas, malaria research is most frequently published in OA and in
      international collaboration. The adjusted regression analyses show that holding
      other factors constant, publishing research in OA and in international
      collaboration has a significant and meaningful citation advantage over non-OA or
      non-international collaborative research. Publishing papers as part of a European
      wide or European- sub-Saharan African collaboration increases research impact. In
      contrast, such collaboration advantage is not observed for research output
      involving sub-Saharan Africa only which seems to decrease research impact.
      CONCLUSIONS: Our results indicate that there is a real, measurable citation
      advantage for publishing PRD research in OA and international collaboration.
      However, the international collaboration advantage seems to be region-specific
      with increased research impact for European-wide and European-sub-Saharan African
      collaborations but a decrease in research impact of collaborations confined to
      sub-Saharan African research institutions. Further research is required to
      further verify this finding and to understand the underlying factors related to
      this observed decrease in research impact. To target future research capacity
      building activities in sub-Saharan Africa it is important to assess whether the
      observed decreased impact reflects the scientific competencies and geographic
      distribution of individual researchers or institutional-, national- or funder
      specific research requirements.

PMID- 30231043
TI  - Assessing the spatiotemporal interactions of mesopredators in Sumatra's tropical
      rainforest.
AB  - Co-occurrence between mesopredators can be achieved by differentiation of prey,
      temporal activity, and spatial habitat use. The study of mesopredator
      interactions is a growing area of research in tropical forests and shedding new
      light on inter-guild competition between threatened vertebrate species that were
      previously little understood. Here, we investigate sympatry between the Sunda
      clouded leopard (Neofelis diardi) and Asiatic golden cat (Pardofelis temminckii)
      living in the Sumatran rainforests of Indonesia. We investigate: i) spatial
      overlap of predator-prey species using a combination of single-species occupancy
      modelling and Bayesian two-species modelling, while controlling for the possible
      influence of several confounding landscape variables; and, ii) temporal overlap
      between mesopredators and their shared prey through calculating their kernel
      density estimate associations. From four study areas, representing lowland, hill,
      sub-montane and montane forest, 28,404 camera trap nights were sampled. Clouded
      leopard and golden cat were respectively detected in 24.3% and 22.6% of the 292
      sampling sites (camera stations) and co-occurred in 29.6% of the sites where they
      were detected. Golden cat occupancy was highest in the study area where clouded
      leopard occupancy was lowest and conversely lowest in the study area where
      clouded leopard occupancy was highest. However, our fine-scale (camera trap site)
      analyses found no evidence of avoidance between these two felid species. While
      both mesopredators exhibited highest spatial overlap with the larger-bodied prey
      species, temporal niche separation was also found. Clouded leopard was more
      nocturnal and, consequently, had higher temporal overlap with the more nocturnal
      prey species, such as porcupine and mouse deer, whereas the more diurnal golden
      cat had higher overlap with the strictly diurnal great argus pheasant. The
      Bayesian two species occupancy modelling approach applied in our study fills
      several important knowledge gaps of Sumatra's lesser known mesopredators and
      provides a replicable methodology for studying interspecific competition for
      other small-medium sized carnivore species in the tropics.

PMID- 30231045
TI  - Rutin derivatives obtained by transesterification reactions catalyzed by Novozym
      435: Antioxidant properties and absence of toxicity in mammalian cells.
AB  - Flavonoids are one of the most important and diversified phenolic groups among
      products of natural origin. An important property of this metabolite class is the
      antioxidant action. This study evaluated the antioxidant and cytotoxic activities
      and oxidative stress of transesterification products of the flavonoid rutin,
      catalyzed by Novozym(r) 435. The presence of monoacetate and diacetate was
      confirmed by quantitative evaluation of the retention times (rutin, 15.68 min;
      rutin monoacetate, 18.14 min; and rutin diacetate, 18.57 min) and by the data
      from LC-MS and NMR 1H and 13C. The experiment showed excellent conversion values
      of 96% in total acetates (rutin monoacetate and diacetate). These results
      confirmed that rutin derivatives have antioxidant potential, as evaluated by the
      ORAC method (rutin standard: 0.53 +/- 0.08 MUM Trolox/g and rutin derivatives:
      2.33 +/- 1.08 MUM Trolox/g) and also show low cytotoxicity in human and animal
      cells. Rutin derivatives reduced the production of reactive oxygen species in RAW
      macrophages as well. Many qualities attributed to rutin derivatives make them
      promising potential candidates for use as nutraceuticals, including their high
      amounts of antioxidants, biological potential and low toxicity, which contribute
      to the reduction of oxidative stress.

PMID- 30231046
TI  - Best practices for standardized performance testing of infrared thermographs
      intended for fever screening.
AB  - Infrared (IR) modalities represent the only currently viable mass fever screening
      approaches for outbreaks of infectious disease pandemics such as Ebola virus
      disease and severe acute respiratory syndrome. Non-contact IR thermometers
      (NCITs) and IR thermographs (IRTs) have been used for fever screening in public
      areas such as airports. While NCITs remain a more popular choice than IRTs, there
      has been increasing evidences in the literature that IRTs can provide great
      accuracy in estimating body temperature if qualified systems are used and
      appropriate procedures are consistently applied. In this study, we addressed the
      issue of IRT qualification by implementing and evaluating a battery of test
      methods for objective, quantitative assessment of IRT performance based on a
      recent international standard (IEC 80601-2-59). We tested two commercial IRTs to
      evaluate their stability and drift, image uniformity, minimum resolvable
      temperature difference, and radiometric temperature laboratory accuracy. Based on
      these tests, we illustrated how experimental and data processing procedures could
      affect results, and suggested methods for clarifying and optimizing test methods.
      Overall, the insights into thermograph standardization and acquisition methods
      provided by this study may improve the utility of IR thermography and aid in
      comparing IRT performance, thus improving the potential for producing high
      quality disease pandemic countermeasures.

PMID- 30231042
TI  - Development of a complex intervention for early integration of palliative home
      care into standard care for end-stage COPD patients: A Phase 0-I study.
AB  - BACKGROUND: Research suggests that palliative home care should be integrated
      early into standard care for end-stage COPD patients. Patients also express the
      wish to be cared for and to die at home. However, a practice model for early
      integration of palliative home care (PHC) into standard care for end-stage COPD
      has not been fully developed. AIM: To develop an intervention for early
      integration of PHC into standard care for end-stage COPD patients. METHODS: We
      conducted a Phase 0-I study according to the Medical Research Council Framework
      for the development of complex interventions. Phase 0 aimed to identify the
      inclusion criteria and key components of the intervention by way of an
      explorative literature search of interventions, expert consultations, and seven
      focus groups with general practitioners and community nurses on perceived
      barriers to and facilitators of early integrated PHC for COPD. In Phase 1, the
      intervention, its inclusion criteria and its components were developed and
      further refined by an expert panel and two expert opinions. RESULTS: Phase 0
      resulted in identification of inclusion criteria and components from existing
      interventions, and barriers to and facilitators of early integration of PHC for
      end-stage COPD. Based on these findings, a nurse-led intervention was developed
      in Phase I consisting of training for PHC nurses in symptom recognition and
      physical therapy exercises for end-stage COPD, regular visits by PHC nurses at
      the patients' homes, two information leaflets on self-management, a semi
      structured protocol and follow-up plan to record the outcomes of the home visits,
      and integration of care by enabling collaboration and communication between home
      and hospital-based professional caregivers. CONCLUSION: This Phase 0-I trial
      succeeded in developing a complex intervention for early integration of PHC for
      end-stage COPD. The use of three methods in Phase 0 gave reliable data on which
      to base inclusion criteria and components of the intervention. The preliminary
      effectiveness, feasibility and acceptability of the intervention will be
      subsequently tested in a Phase II study.

PMID- 30231047
TI  - Ultrastructure of Meelsvirus: A nuclear virus of arrow worms (phylum
      Chaetognatha) producing giant "tailed" virions.
AB  - Most known giant viruses, i.e., viruses producing giant virions, parasitize
      amoebae and other unicellular eukaryotes. Although they vary in the level of
      dependence on host nuclear functions, their virions self-assemble in the host
      cell's cytoplasm. Here we report the discovery of a new prototype of giant virus
      infecting epidermal cells of the marine arrow worm Adhesisagitta hispida. Its
      1.25 MUm-long virions self-assemble and accumulate in the host cell's nucleus.
      Conventional transmission electron microscopy reveals that the virions have a
      unique bipartite structure. An ovoid nucleocapsid, situated in a broad "head" end
      of the virion is surrounded by a thin envelope. The latter extends away from the
      head to form a voluminous conical "tail" filled with electron-dense
      extracapsidular material. The 31nm-thick capsid wall has a distinctive
      substructure resulting from a patterned arrangement of subunits; it bears no
      ultrastructural resemblance to the virion walls of other known giant viruses. The
      envelope self-assembles coincident with the capsid and remotely from all host
      membranes. We postulate that transmission to new hosts occurs by rupture of
      protruding virion-filled nuclei when infected arrow worms mate. Future genomic
      work is needed to determine the phylogenetic position of this new virus, which we
      have provisionally named Meelsvirus.

PMID- 30231048
TI  - Rainfall trends and variation in the Maasai Mara ecosystem and their implications
      for animal population and biodiversity dynamics.
AB  - Rainfall exerts a controlling influence on the availability and quality of
      vegetation and surface water for herbivores in African terrestrial ecosystems. We
      analyse temporal trends and variation in rainfall in the Maasai Mara ecosystem of
      East Africa and infer their implications for animal population and biodiversity
      dynamics. The data originated from 15 rain gauges in the Mara region (1965-2015)
      and one station in Narok Town (1913-2015), in Kenya's Narok County. This is the
      first comprehensive and most detailed analysis of changes in rainfall in the
      region of its kind. Our results do not support the current predictions of the
      International Panel of Climate Change (IPCC) of very likely increases of rainfall
      over parts of Eastern Africa. The dry season rainfall component increased during
      1935-2015 but annual rainfall decreased during 1962-2015 in Narok Town. Monthly
      rainfall was more stable and higher in the Mara than in Narok Town, likely
      because the Mara lies closer to the high-precipitation areas along the shores of
      Lake Victoria. Predominantly deterministic and persistent inter-annual cycles and
      extremely stable seasonal rainfall oscillations characterize rainfall in the Mara
      and Narok regions. The frequency of severe droughts increased and floods
      intensified in the Mara but droughts became less frequent and less severe in
      Narok Town. The timings of extreme droughts and floods coincided with significant
      periodicity in rainfall oscillations, implicating strong influences of global
      atmospheric and oceanic circulation patterns on regional rainfall variability.
      These changing rainfall patterns have implications for animal population
      dynamics. The increase in dry season rainfall during 1935-2015 possibly
      counterbalanced the impacts of resource scarcity generated by the declining
      annual rainfall during 1965-2015 in Narok Town. However, the increasing rainfall
      extremes in the Mara can be expected to create conditions conducive to outbreaks
      of infectious animal diseases and reduced vegetation quality for herbivores,
      particularly when droughts and floods persist over multiple years. The more
      extreme wet season rainfall may also alter herbivore space use, including
      migration patterns.

PMID- 30231049
TI  - Genetic analysis of resistance to stripe rust in durum wheat (Triticum turgidum
      L. var. durum).
AB  - Stripe rust, caused by the fungal pathogen Puccinia striiformis Westend. f. sp.
      tritici Eriks, is an important disease of bread wheat (Triticum aestivum L.)
      worldwide and there is an indication that it may also become a serious disease of
      durum wheat (T. turgidum L. var. durum). Therefore, we investigated the genetic
      architecture underlying resistance to stripe rust in adapted durum wheat
      germplasm. Wheat infection assays were conducted under controlled conditions in
      Canada and under field conditions in Mexico. Disease assessments were performed
      on a population of 155 doubled haploid (DH) lines derived from the cross of Kofa
      (susceptible) and W9262-260D3 (moderately resistant) and on a breeding panel that
      consisted of 92 diverse cultivars and breeding lines. Both populations were
      genotyped using the 90K single-nucleotide polymorphism (SNP) iSelect assay. In
      the DH population, QTL for stripe rust resistance were identified on chromosome
      7B (LOD 6.87-11.47) and chromosome 5B (LOD 3.88-9.17). The QTL for stripe rust
      resistance on chromosome 7B was supported in the breeding panel. Both QTL were
      anchored to the genome sequence of wild emmer wheat, which identified gene
      candidates involved in disease resistance. Exome capture sequencing identified
      variation in the candidate genes between Kofa and W9262-260D3. These genetic
      insights will be useful in durum breeding to enhance resistance to stripe rust.

PMID- 30231050
TI  - Tubulin's response to external electric fields by molecular dynamics simulations.
AB  - Tubulin heterodimers are the building blocks of microtubules and disruption of
      their dynamics is exploited in the treatment of cancer. Electric fields at
      certain frequencies and magnitudes are believed to do the same. Here, the tubulin
      dimer's response to external electric fields was determined by atomistic
      simulation. External fields from 50 to 750 kV/cm, applied for 10 ns, caused
      significant conformational rearrangements that were dependent upon the field's
      directionality. Charged and flexible regions, including the alpha:H1-B2 loop,
      beta:M-loop, and C-termini, were susceptible. Closer inspection of the alpha:H1
      B2 loop in lower strength fields revealed that these effects were consistent and
      proportional to field strength, and the findings indicate that external electric
      fields modulate the stability of microtubules through conformational changes to
      key loops involved in lateral contacts. We also find evidence that tubulin's
      curvature and elongation are affected, and external electric fields may bias
      tubulin towards depolymerization.

PMID- 30231051
TI  - Can patient-reported profiles avoid unnecessary referral to a spine surgeon? An
      observational study to further develop the Nijmegen Decision Tool for Chronic Low
      Back Pain.
AB  - INTRODUCTION: Chronic Low Back Pain (CLBP) is a heterogeneous condition with lack
      of diagnostic clarity. Therapeutic interventions show small effects. To improve
      outcomes by targeting interventions it is recommended to develop a triage system
      to surgical and non-surgical treatments based on treatment outcomes. The
      objective of the current study was to develop and internally validate prognostic
      models based on pre-treatment patient-reported profiles that identify patients
      who either respond or do not respond to two frequently performed treatments
      (lumbar spine surgery and multidisciplinary pain management program). METHODS: A
      consecutive cohort study in a secondary referral spine center was performed. The
      study followed the recommendations of the PROGRESS framework and was registered
      in the Dutch Trial Register (NTR5946). Data of forty-seven potential pre
      consultation (baseline) indicators predicting 'response' or 'non-response' at one
      year follow-up for the two treatments were obtained to develop and validate four
      multivariable logistic regression models. The source population consisted of
      3,410 referred CLBP-patients. Two treatment cohorts were defined: elective 'spine
      surgery' (n = 217 [6.4%]) and multidisciplinary bio-psychosocial 'pain management
      program' (n = 171 [5.0%]). Main inclusion criteria were age >=18, CLBP (>=6
      months), and not responding to primary care treatment. The primary outcome was
      functional ability: 'response' (Oswestry Disability Index [ODI] <=22) and 'non
      response' (ODI >=41). RESULTS: Baseline indicators predictive of treatment
      outcome were: degree of disability (all models), >=2 previous spine surgeries,
      psychosocial complaints, age (onset <20 or >50), and patient expectations of
      treatment outcomes. The explained variances were low for the models predicting
      response and non-response to pain management program (R2 respectively 23% and
      26%) and modest for surgery (R2 30% and 39%). The overall performance was
      acceptable (c-index; 0.72-0.83), the model predicting non-response to surgery
      performed best (R2 = 39%; c-index = 0.83). CONCLUSION: This study was the first
      to identify different patient-reported profiles that predict response to
      different treatments for CLBP. The model predicting 'non-response' to elective
      lumbar spine surgery performed remarkably well, suggesting that referrals of
      these patients to a spine surgeon could be avoided. After external validation,
      the patient-reported profiles could potentially enhance timely patient triage to
      the right secondary care specialist and improve decision-making between clinican
      and patient. This could lead to improved treatment outcomes, which results in a
      more efficient use of healthcare resources.

PMID- 30231052
TI  - The efficacy and safety of dexmedetomidine in cardiac surgery patients: A
      systematic review and meta-analysis.
AB  - This study aimed to evaluate the efficacy and safety of dexmedetomidine versus
      any other treatment without dexmedetomidine in patients who have undergone
      cardiac surgery. Electronic databases including PubMed, Embase, and Cochrane
      Library were systematically searched without limitations of language and
      publication time. Randomized controlled trials (RCTs) aiming to evaluate the
      efficacy and safety of dexmedetomidine versus any other treatment without
      dexmedetomidine in patients that have undergone cardiac surgery were selected.
      Endpoints such as hemodynamic indexes and adverse events in eligible studies were
      extracted by two researchers, independently. The data was analyzed using RevMan
      5.3 and Stata 11.0 software. A total of 18 RCTs met the inclusion criteria,
      involving 1730 patients. Compared to control (any treatment without
      dexmedetomidine), dexmedetomidine showed a pooled mean difference (MD) of -14.46
      [95% confidence interval(CI): -24.69, -4.23; p<0.01] for systolic arterial
      pressure, a standardized mean difference (SMD) of -1.74 for mean arterial blood
      pressure (95% CI: -2.80, -0.68; P < 0.01), -2.12 (95%CI: -3.23, -1.00; p<0.01)
      for heart rate, and combined odds ratio (OR) of 0.22 (95%CI: 0.11, 0.44; p<0.01)
      for tachycardia, 3.44 (95%CI: 1.95, 5.96; p<0.01) for bradycardia, 0.74 (95%CI:
      0.49, 1.12; p>0.05) for atrial fibrillation, and 0.99 (95%CI: 0.51, 1.90; p>0.05)
      for hypotension. In addition, dexmedetomidine could reduce time of surgery and
      stay in intensive care units, improve delirium with good safety. Our study shows
      clinical application of dexmedetomidine in cardiac surgery patients can reduce
      risks of abnormal hemodynamics with good safety.

PMID- 30231053
TI  - Strength, microstructure, and thermal conductivity of the insulation wallboards
      prepared with rice husk fiber and recycled concrete aggregates.
AB  - This paper intends to evaluate the influence of content of rice husk fiber and
      cementitious materials on mechanical properties and thermal conductivity of
      thermal insulation wallboards. Thermal insulation wallboard contained different
      mass of rice husk fiber was prepared when the weight of cement, fly ash,
      cellulose ether, naphthalene superplasticizer, and recycled concrete aggregates
      was equal. Scanning electron microscopy (SEM) shows the internal structure of the
      insulation wallboards is very dense. Compared to thermal conductivity of blank
      group (0.9600 W/m. degrees C), B2 (0.1997 W/m. degrees C) and C2 (0.1810 W/m.
      degrees C) measured by the DRCD-3030 intelligent thermal conductivity tester can
      meet certain engineering requirements. Average compressive strength, flexural
      strength, and thermal conductivity of wallboards decreases with content of rice
      husk fiber increasing when other materials mass are the same. Under the same
      conditions of curing time and rice husk content, average compressive and flexural
      strength increase with the increase of the amount of cementitious material.

PMID- 30231054
TI  - Published estimates of group differences in multisensory integration are
      inflated.
AB  - A common measure of multisensory integration is the McGurk effect, an illusion in
      which incongruent auditory and visual speech are integrated to produce an
      entirely different percept. Published studies report that participants who differ
      in age, gender, culture, native language, or traits related to neurological or
      psychiatric disorders also differ in their susceptibility to the McGurk effect.
      These group-level differences are used as evidence for fundamental alterations in
      sensory processing between populations. Using empirical data and statistical
      simulations tested under a range of conditions, we show that published estimates
      of group differences in the McGurk effect are inflated when only statistically
      significant (p < 0.05) results are published. With a sample size typical of
      published studies, a group difference of 10% would be reported as 31%. As a
      consequence of this inflation, follow-up studies often fail to replicate
      published reports of large between-group differences. Inaccurate estimates of
      effect sizes and replication failures are especially problematic in studies of
      clinical populations involving expensive and time-consuming interventions, such
      as training paradigms to improve sensory processing. Reducing effect size
      inflation and increasing replicability requires increasing the number of
      participants by an order of magnitude compared with current practice.

PMID- 30231055
TI  - Oxygen conserving mitochondrial adaptations in the skeletal muscles of breath
      hold divers.
AB  - BACKGROUND: The performance of elite breath hold divers (BHD) includes static
      breath hold for more than 11 minutes, swimming as far as 300 m, or going below
      250 m in depth, all on a single breath of air. Diving mammals are adapted to
      sustain oxidative metabolism in hypoxic conditions through several metabolic
      adaptations, including improved capacity for oxygen transport and mitochondrial
      oxidative phosphorylation in skeletal muscle. It was hypothesized that similar
      adaptations characterized human BHD. Hence, the purpose of this study was to
      examine the capacity for oxidative metabolism in skeletal muscle of BHD compared
      to matched controls. METHODS: Biopsies were obtained from the lateral vastus of
      the femoral muscle from 8 Danish BHD and 8 non-diving controls (Judo athletes)
      matched for morphometry and whole body VO2max. High resolution respirometry was
      used to determine mitochondrial respiratory capacity and leak respiration with
      simultaneous measurement of mitochondrial H2O2 emission. Maximal citrate synthase
      (CS) and 3-hydroxyacyl CoA dehydrogenase (HAD) activity were measured in muscle
      tissue homogenates. Western Blotting was used to determine protein contents of
      respiratory complex I-V subunits and myoglobin in muscle tissue lysates. RESULTS:
      Muscle biopsies of BHD revealed lower mitochondrial leak respiration and electron
      transfer system (ETS) capacity and higher H2O2 emission during leak respiration
      than controls, with no differences in enzyme activities (CS and HAD) or protein
      content of mitochondrial complex subunits myoglobin, myosin heavy chain isoforms,
      markers of glucose metabolism and antioxidant enzymes. CONCLUSION: We
      demonstrated for the first time in humans, that the skeletal muscles of BHD are
      characterized by lower mitochondrial oxygen consumption both during low leak and
      high (ETS) respiration than matched controls. This supports previous observations
      of diving mammals demonstrating a lower aerobic mitochondrial capacity of the
      skeletal muscles as an oxygen conserving adaptation during prolonged dives.

PMID- 30231056
TI  - Is India ready for mental health apps (MHApps)? A quantitative-qualitative
      exploration of caregivers' perspective on smartphone-based solutions for managing
      severe mental illnesses in low resource settings.
AB  - BACKGROUND: Mobile application based delivery of psycho-social interventions may
      help reduce the treatment gap for severe mental illnesses (SMIs) and decrease the
      burden on caregivers. Apps developed in high income settings show effectiveness,
      but they suffer from lack of applicability in low resource scenarios due to the
      difference in technology penetration, affordability, and acceptance. OBJECTIVE:
      This study aimed to understand health technology usage, perceived needs, and
      acceptability of app based interventions in patients with SMIs to improve illness
      management and reduce caregiver burden. METHODS: The study was conducted in
      inpatient and outpatient settings of a tertiary care center in North India. A
      cross-sectional survey assessed smartphone and health app usage. Further, three
      focus group discussions evaluated the needs and apprehensions in using apps in
      management of SMIs. RESULTS: A total of 176 participants including 88 patients
      and 88 caregivers completed the survey. Smartphone ownership was similar to the
      national average (30%) in both caregivers (38.6%) and in patients (31.8%).
      Although subjects regularly used a third party app, health app usage was very
      low. Cost, unfamiliarity, and language were significant barriers to adoption. The
      focus group discussions provided insight into the various apprehensions of
      caregivers in using and in allowing patients to use smartphones and such apps.
      Caregivers wanted mobile apps for accessing information regarding services and
      resources available for people with SMI, and they felt such apps can be helpful
      if they could automate some of their routine caregiving activities. However, the
      significant difficulty was perceived in regards to the cost of the device,
      language of the medium, and unfamiliarity in using technology. Apprehensions that
      SMI patients might misuse technology, or damage the device were also prevalent.
      CONCLUSIONS: The study systematically looks into the scope, design considerations
      and limitations of implementing a mobile technology based intervention for low
      resource settings. With only one-third of the patients and caregivers having
      access to smartphones and internet, parallel outreach strategies like IVRS should
      be actively considered while designing interventions. The difficulty of
      understanding and searching in a non-native language needs to be addressed. Hand
      holding of caregivers and frequent encouragement from treating doctors might
      significantly help in technology adoption and in surmounting the apprehensions
      related to using technology. To make the solution acceptable and useful to the
      already over-burdened caregivers, developers need to work closely with patients'
      family members and follow a ground-up collaborative approach to app development.
      The scope of delivering mental health services through technology is immense in
      resource constrained settings like India, provided we, researchers, appreciate
      and accept the fact that in the varied landscape of a divergent economic,
      educational, and cultural milieu, a single solution will never suffice for all,
      and intervention modality matching with end user capacity will be of paramount
      importance in determining the success of the endeavor.

PMID- 30231058
TI  - Bedrock geology affects foliar nutrient status but has minor influence on leaf
      carbon isotope discrimination across altitudinal gradients.
AB  - Carbon isotope discrimination (Delta13C) in plant leaves generally decreases with
      increasing altitude in mountains. Lower foliar Delta13C at high elevation usually
      is associated with higher leaf mass per area (LMA) in thicker leaves. However, it
      is unclear if lower foliar Delta13C in high-altitude plants is caused by improved
      photosynthetic capacity as an effect of higher nutrient, especially nitrogen,
      content in thicker leaves. We investigated trends of foliar Delta13C in four
      species, each belonging to a different plant functional type (PFT), across two
      altitudinal gradients, each on a different bedrock type (carbonate and silicate
      bedrock, respectively) in a region of the southern Alps (Italy) where the foliar
      Delta13C was not affected by water limitation. Our objective was to assess
      whether the altitudinal patterns of foliar Delta13C in relation to leaf
      morphology and foliar nutrients were conditioned by indirect control of bedrock
      geology on soil nutrient availability. The foliar Delta13C of the four species
      was mainly affected by LMA and, secondarily, by stomatal density (SD) but the
      relative importance of these foliar traits varied among species. Area-based
      nutrient contents had overall minor importance in controlling C discrimination.
      Relationships among foliar Delta13C, foliar nutrient content and leaf growth rate
      strongly depended on soil nutrient availability varying differently across the
      two gradients. In the absence of water limitation, the foliar Delta13C was
      primarily controlled by irradiance which can shape anatomical leaf traits,
      especially LMA and/or SD, whose relative importance in determining C isotope
      discrimination differed among species and/or PFT. Decreasing foliar Delta13C
      across altitudinal gradients need not be determined by improved photosynthetic
      capacity deriving from higher nutrient content in thicker leaves.

PMID- 30231059
TI  - Diversity of miniaturized frogs of the genus Adelophryne (Anura:
      Eleutherodactylidae): A new species from the Atlantic Forest of northeast Brazil.
AB  - The number of species of frogs in the South American genus Adelophryne has
      increased in recent years, and it has become apparent that this group contains a
      substantial amount of undescribed diversity. Currently the genus contains nine
      described species and five candidate species. Here we describe the tenth species
      of the genus Adelophryne from the municipality of Igrapiuna, southern Bahia
      state, Brazil. The new species is characterized by its small body size,
      indistinct tympanum, and two phalanges in the finger IV. The species of the genus
      are distributed in three groups, Northern Amazonia Clade, Northern Atlantic
      Forest Clade and Southern Atlantic Forest Clade. The new species is
      phylogenetically related to species of the Northern Atlantic Forest Clade of
      Adelophryne and restricted to forested habitat, as typical for other Adelophryne.
      The species is restricted to the pristine forests in the type locality, and we
      consider its conservation status as Near Threatened. New morphological and
      molecular data of other Adelophryne species are presented, extending the
      distribution of Adelophryne sp. 2, Adelophryne sp. 4, Adelophryne mucronata and
      Adelophryne glandulata. However, a more comprehensive revision of the diversity
      and phylogenetic position of most Adelophryne species is needed, and the
      evolutionary relationships of A. meridionalis and A. pachydactyla remain unknown.

PMID- 30231057
TI  - Prediction of leprosy in the Chinese population based on a weighted genetic risk
      score.
AB  - Genome wide association studies (GWASs) have revealed multiple genetic variants
      associated with leprosy in the Chinese population. The aim of our study was to
      utilize the genetic variants to construct a risk prediction model through a
      weighted genetic risk score (GRS) in a Chinese set and to further assess the
      performance of the model in identifying higher-risk contact individuals in an
      independent set. The highest prediction accuracy, with an area under the curve
      (AUC) of 0.743 (95% confidence interval (CI): 0.729-0.757), was achieved with a
      GRS encompassing 25 GWAS variants in a discovery set that included 2,144 people
      affected by leprosy and 2,671 controls. Individuals in the high-risk group, based
      on genetic factors (GRS > 28.06), have a 24.65 higher odds ratio (OR) for
      developing leprosy relative to those in the low-risk group (GRS<=18.17). The
      model was then applied to a validation set consisting of 1,385 people affected by
      leprosy and 7,541 individuals in contact with leprosy, which yielded a
      discriminatory ability with an AUC of 0.707 (95% CI: 0.691-0.723). When a GRS cut
      off value of 22.38 was selected with the optimal sensitivity and specificity, it
      was found that 39.31% of high risk contact individuals should be screened in
      order to detect leprosy in 64.9% of those people affected by leprosy. In summary,
      we developed and validated a risk model for the prediction of leprosy that showed
      good discrimination capabilities, which may help physicians in the identification
      of patients coming into contact with leprosy and are at a higher-risk of
      developing this condition.

PMID- 30231061
TI  - Correction: Induction of circulating T follicular helper cells and regulatory T
      cells correlating with HIV-1 gp120 variable loop antibodies by a subtype C
      prophylactic vaccine tested in a Phase I trial in India.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0203037.].

PMID- 30231060
TI  - Subgingival microbiome of rheumatoid arthritis patients in relation to their
      disease status and periodontal health.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory
      diseases that share common risk factors. However, the bidirectional relationship
      between RA and periodontal disease is not fully understood. This study was
      undertaken to describe the bacterial component of the subgingival microbiome in
      RA patients and to relate this to RA disease activity and periodontal status.
      METHODS: Patients with chronic established RA (N = 78) were periodontally
      examined and their subgingival plaque samples were collected; their clinical and
      laboratory data on RA status and medication were obtained from medical records.
      Bacterial DNA was quantified by universal 16S rDNA qPCR, and Porphyromonas
      gingivalis by species-specific qPCR. For microbiome assessment, 16S rDNA amplicon
      sequencing was performed. RESULTS: Active RA was diagnosed in 58% of the patients
      and periodontitis in 82% (mild: 9%, moderate: 55%, severe: 18%). P. gingivalis
      was present in 14% of the samples. Different levels of gingival bleeding,
      periodontal probing depth, RA disease status, prednisolone use and smoking were
      associated with significantly different microbiome compositions. Two subgingival
      microbial community types were discerned. CONCLUSION: In RA patients with active
      disease, anti-inflammatory medication as part of RA therapy was associated with
      better oral health status and a healthier subgingival microbiome compared to that
      of RA patients in remission, especially those in remission who were current
      smokers. RA patients in remission with current smoking status may particularly
      benefit from a systematic periodontal treatment program. The potential role of
      microbial community types in patient stratification and personalized therapy
      should be assessed in longitudinal studies.

PMID- 30231063
TI  - Loss of the Spinocerebellar Ataxia type 3 disease protein ATXN3 alters
      transcription of multiple signal transduction pathways.
AB  - Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative
      disorder caused by a polyglutamine-encoding CAG repeat expansion in the ATXN3
      gene which encodes the deubiquitinating enzyme, ATXN3. Several mechanisms have
      been proposed to explain the pathogenic role of mutant, polyQ-expanded ATXN3 in
      SCA3 including disease protein aggregation, impairment of ubiquitin-proteasomal
      degradation and transcriptional dysregulation. A better understanding of the
      normal functions of this protein may shed light on SCA3 disease pathogenesis. To
      assess the potential normal role of ATXN3 in regulating gene expression, we
      compared transcriptional profiles in WT versus Atxn3 null mouse embryonic
      fibroblasts. Differentially expressed genes in the absence of ATXN3 contribute to
      multiple signal transduction pathways, suggesting a status switch of signaling
      pathways including depressed Wnt and BMP4 pathways and elevated growth factor
      pathways such as Prolactin, TGF-beta, and Ephrin pathways. The Eph receptor A3
      (Efna3), a receptor protein-tyrosine kinase in the Ephrin pathway that is highly
      expressed in the nervous system, was the most differentially upregulated gene in
      Atxn3 null MEFs. This increased expression of Efna3 was recapitulated in Atxn3
      knockout mouse brainstem, a selectively vulnerable brain region in SCA3.
      Overexpression of normal or expanded ATXN3 was sufficient to repress Efna3
      expression, supporting a role for ATXN3 in regulating Ephrin signaling. We
      further show that, in the absence of ATXN3, Efna3 upregulation is associated with
      hyperacetylation of histones H3 and H4 at the Efna3 promoter, which in turn is
      induced by decreased levels of HDAC3 and NCoR in ATXN3 null cells. Together,
      these results reveal a normal role for ATXN3 in transcriptional regulation of
      multiple signaling pathways of potential relevance to disease processes in SCA3.

PMID- 30231062
TI  - Bone remodeling: A tissue-level process emerging from cell-level molecular
      algorithms.
AB  - The human skeleton undergoes constant remodeling throughout the lifetime.
      Processes occurring on microscopic and molecular scales degrade bone and replace
      it with new, fully functional tissue. Multiple bone remodeling events occur
      simultaneously, continuously and independently throughout the body, so that the
      entire skeleton is completely renewed about every ten years.Bone remodeling is
      performed by groups of cells called Bone Multicellular Units (BMU). BMUs consist
      of different cell types, some specialized in the resorption of old bone, others
      encharged with producing new bone to replace the former. These processes are
      tightly regulated so that the amount of new bone produced is in perfect
      equilibrium with that of old bone removed, thus maintaining bone microscopic
      structure.To date, many regulatory molecules involved in bone remodeling have
      been identified, but the precise mechanism of BMU operation remains to be fully
      elucidated. Given the complexity of the signaling pathways already known, one may
      question whether such complexity is an inherent requirement of the process or
      whether some subset of the multiple constituents could fulfill the essential
      role, leaving functional redundancy to serve an alternative safety role. We
      propose in this work a minimal model of BMU function that involves a limited
      number of signals able to account for fully functional BMU operation. Our main
      assumptions were i) at any given time, any cell within a BMU can select only one
      among a limited choice of decisions, i.e. divide, die, migrate or differentiate,
      ii) this decision is irreversibly determined by depletion of an appropriate
      internal inhibitor and iii) the dynamics of any such inhibitor are coupled to
      that of specific external mediators, such as hormones, cytokines, growth factors.
      It was thus shown that efficient BMU operation manifests as an emergent process,
      which results from the individual and collective decisions taken by cells within
      the BMU unit in the absence of any external planning.

PMID- 30231064
TI  - A multiple hypothesis approach to explain species richness patterns in
      neotropical stream-dweller fish communities.
AB  - Several hypotheses are used to explain species richness patterns. Some of them
      (e.g. species-area, species-energy, environment-energy, water-energy, terrestrial
      primary productivity, environmental spatial heterogeneity, and climatic
      heterogeneity) are known to explain species richness patterns of terrestrial
      organisms, especially when they are combined. For aquatic organisms, however, it
      is unclear if these hypotheses can be useful to explain for these purposes.
      Therefore, we used a selection model approach to assess the predictive capacity
      of such hypotheses, and to determine which of them (combined or not) would be the
      most appropriate to explain the fish species distribution in small Brazilian
      streams. We perform the Akaike's information criteria for models selections and
      the eigenvector analysis to control the special autocorrelation. The spatial
      structure was equal to 0.453, Moran's I, and require 11 spatial filters. All
      models were significant and had adjustments ranging from 0.370 to 0.416 with
      strong spatial component (ranging from 0.226 to 0.369) and low adjustments for
      environmental data (ranging from 0.001 to 0.119) We obtained two groups of
      hypothesis are able to explain the richness pattern (1) water-energy, temporal
      productivity-heterogeneity (AIC = 4498.800) and (2) water-energy, temporal
      productivity-heterogeneity and area (AIC = 4500.400). We conclude that the fish
      richness patterns in small Brazilian streams are better explained by a
      combination of Water-Energy + Productivity + Temporal Heterogeneity hypotheses
      and not by just one.

PMID- 30231066
TI  - The presence of depression in de novo Parkinson's disease reflects poor motor
      compensation.
AB  - Depression frequently accompanies Parkinson's disease and often precedes the
      onset of motor symptoms. This study aimed to evaluate the impact of depression on
      motor compensation in patients with de novo Parkinson's disease. This
      retrospective cohort study analyzed data from 474 non-demented patients with de
      novo Parkinson's disease (mean age, 64.6+/-9.8 years; 242 men) who underwent both
      dopamine transporter PET scan and depression assessment using the Beck Depression
      Inventory at baseline. Patients were classified into tertiles by Beck Depression
      Inventory score. At baseline, high-tertile group (Beck Depression Inventory score
      >=15, n = 157) showed more severe motor deficits and lower cognitive function
      than low-tertile group (Beck Depression Inventory score <=7, n = 158, P = 0.034
      and P = 0.008, respectively). Greater motor deficits in high-tertile group than
      low-tertile group remained significant after controlling for dopamine transporter
      binding in the posterior putamen, as well as other confounding variables. During
      follow-up of a median duration of 47 months, high-tertile group received higher
      levodopa-equivalent doses for symptom control than did low-tertile group after
      controlling for age, gender, and initial motor deficit severity. These results
      demonstrate that depression in de novo Parkinson's disease is associated with
      motor deficit severity at baseline and dose of PD medications during follow-up,
      suggesting that the presence of depression in de novo Parkinson's disease
      represents poor motor compensation.

PMID- 30231065
TI  - Circulating HLA-DR+CD4+ effector memory T cells resistant to CCR5 and PD-L1
      mediated suppression compromise regulatory T cell function in tuberculosis.
AB  - Chronic T cell activation is a hallmark of pulmonary tuberculosis (PTB). The
      mechanisms underpinning this important phenomenon are however, poorly elucidated,
      though known to rely on control of T effector cells (Teff) by regulatory T cells
      (Treg). Our studies show that circulating natural Treg cells in adults with PTB
      preserve their suppressive potential but Teff cells from such subjects are
      resistant to Treg-mediated suppression. We found this to be due to expansion of
      an activated Teff subset identified by Human Leukocyte Antigen (HLA)-DR
      expression. Sensitivity to suppression was restored to control levels by
      depletion of this subset. Comparative transcriptome analysis of Teff cells that
      contain HLA-DR+ cells versus the fraction depleted of this population identified
      putative resistance mechanisms linked to IFNG, IL17A, IL22, PD-L1 and beta
      chemokines CCL3L3, CCL4 expression. Antibody blocking experiments confirmed HLA
      DR+ Teff cells, but not the fraction depleted of HLA-DR+ effectors, to be
      resistant to Treg suppression mediated via CCR5 and PD-L1 associated pathways. In
      the presence of HLA-DR+ Teff cells, activation of NFkappaB downstream of CCR5 and
      PD-L1 was perturbed. In addition, HLA-DR+ Teff cells expressed significantly
      higher levels of Th1/Th17 cytokines that may regulate Treg function through a
      reciprocal counter-balancing relationship. Taken together, our study provides
      novel insight on how activated HLA-DR+CD4+ T cells may contribute to disease
      associated inflammation by compromising Treg-mediated suppression in PTB.

PMID- 30231067
TI  - Risk of ischemic stroke and the use of individual non-steroidal anti-inflammatory
      drugs: A multi-country European database study within the SOS Project.
AB  - BACKGROUND AND PURPOSE: A multi-country European study using data from six
      healthcare databases from four countries was performed to evaluate in a large
      study population (>32 million) the risk of ischemic stroke (IS) associated with
      individual NSAIDs and to assess the impact of risk factors of IS and co
      medication. METHODS: Case-control study nested in a cohort of new NSAID users.
      For each case, up to 100 sex- and age-matched controls were selected and
      confounder-adjusted odds ratios for current use of individual NSAIDs compared to
      past use calculated. RESULTS: 49,170 cases of IS were observed among 4,593,778
      new NSAID users. Use of coxibs (odds ratio 1.08, 95%-confidence interval 1.02
      1.15) and use of traditional NSAIDs (1.16, 1.12-1.19) were associated with an
      increased risk of IS. Among 32 individual NSAIDs evaluated, the highest
      significant risk of IS was observed for ketorolac (1.46, 1.19-1.78), but
      significantly increased risks (in decreasing order) were also found for
      diclofenac, indomethacin, rofecoxib, ibuprofen, nimesulide, diclofenac with
      misoprostol, and piroxicam. IS risk associated with NSAID use was generally
      higher in persons of younger age, males, and those with a prior history of IS.
      CONCLUSIONS: Risk of IS differs between individual NSAIDs and appears to be
      higher in patients with a prior history of IS or transient ischemic attack (TIA),
      in younger or male patients. Co-medication with aspirin, other antiplatelets or
      anticoagulants might mitigate this risk. The small to moderate observed risk
      increase (by 13-46%) associated with NSAIDs use represents a public health
      concern due to widespread NSAID usage.

PMID- 30231068
TI  - Age-related accumulation of toxic metals in the human locus ceruleus.
AB  - Damage to the locus ceruleus has been implicated in the pathogenesis of a number
      of neurological conditions. Locus ceruleus neurons accumulate toxic metals such
      as mercury selectively, however, the presence of toxic metals in locus ceruleus
      neurons of people of different ages, and with a variety of disorders, is not
      known. To demonstrate at what age toxic metals are first detectable in the locus
      ceruleus, and to evaluate whether their presence is more common in certain
      clinicopathological conditions, we looked for these metals in 228 locus ceruleus
      samples. Samples were taken at coronial autopsies from individuals with a wide
      range of ages, pre-existing conditions and causes of death. Paraffin sections of
      pons containing the locus ceruleus were stained with silver nitrate
      autometallography, which indicates inorganic mercury, silver and bismuth within
      cells (termed autometallography-detected toxic metals, or AMGTM). No locus
      ceruleus AMG neurons were seen in 38 individuals aged under 20 years. 47% of the
      190 adults (ie, aged 20 years and over) had AMG locus ceruleus neurons. The
      proportion of adults with locus ceruleus AMG neurons increased during aging,
      except for a decreased proportion in the 90-plus years age group. No differences
      were found in the proportions of locus ceruleus AMG neurons between groups with
      different neurological, psychiatric, or other clinicopathological conditions, or
      among various causes of death. Elemental analysis with laser ablation-inductively
      coupled plasma-mass spectrometry was used to cross-validate the metals detected
      by AMG, by looking for silver, gold, bismuth, cadmium, chromium, iron, mercury,
      nickel, and lead in the locus ceruleus of ten individuals. This confirmed the
      presence of mercury in locus ceruleus samples containing AMG neurons, and showed
      cadmium, silver, lead, iron, and nickel in the locus ceruleus of some
      individuals. In conclusion, toxic metals stained by AMG (most likely inorganic
      mercury) appear in locus ceruleus neurons in early adult life. About half of
      adults in this study had locus ceruleus neurons containing inorganic mercury, and
      elemental analysis found a range of other toxic metals in the locus ceruleus.
      Locus ceruleus inorganic mercury increased during aging, except for a decrease in
      advanced age, but was not found more often in any single clinicopathological
      condition or cause of death.

PMID- 30231070
TI  - Wild great and blue tits do not avoid chemical cues of predators when selecting
      cavities for roosting.
AB  - Small birds use cavities for roosting to decrease the thermoregulatory costs
      during the winter nights. The ability of birds to detect and escape from an
      approaching predator is impaired during roosting and thus the selection of such
      cavities should take into account the risk that a predator will find the cavity.
      Previous evidence suggested that birds in captivity are able to detect predator
      scent and avoid roosting in nest-boxes containing such predator chemical cues.
      Here, we tested whether birds also show this avoidance response under natural
      conditions. We performed three studies in three populations of blue and great
      tits. We added predator scent, a pungency scent or an odourless control to nest
      boxes and compared the use of these nest-boxes for roosting. We found no
      differences between the scent treatments in the use of nest-boxes. Therefore,
      chemical cues indicating the potential presence of a predator are not enough for
      birds to avoid roosting in nest-boxes under natural conditions.

PMID- 30231069
TI  - Therapeutic potential of extracellular vesicles derived from human mesenchymal
      stem cells in a model of progressive multiple sclerosis.
AB  - Extracellular vesicles (EVs) have emerged as important mediators of intercellular
      communication and as possible therapeutic agents in inflammation-mediated
      demyelinating diseases, including multiple sclerosis (MS). In the present study,
      we investigated whether intravenously administered EVs derived from mesenchymal
      stem cells (MSCs) from human adipose tissue might mediate recovery in Theiler's
      murine encephalomyelitis virus (TMEV)-induced demyelinating disease, a
      progressive model of MS. SJL/J mice were subjected to EV treatment once the
      disease was established. We found that intravenous EV administration improved
      motor deficits, reduced brain atrophy, increased cell proliferation in the
      subventricular zone and decreased inflammatory infiltrates in the spinal cord in
      mice infected with TMEV. EV treatment was also capable of modulating
      neuroinflammation, given glial fibrillary acidic protein and Iba-1 staining were
      reduced in the brain, whereas myelin protein expression was increased. Changes in
      the morphology of microglial cells in the spinal cord suggest that EVs also
      modulate the activation state of microglia. The clear reduction in plasma
      cytokine levels, mainly in the Th1 and Th17 phenotypes, in TMEV mice treated with
      EVs confirms the immunomodulatory ability of intravenous EVs. According to our
      results, EV administration attenuates motor deficits through immunomodulatory
      actions, diminishing brain atrophy and promoting remyelination. Further studies
      are necessary to establish EV delivery as a possible therapy for the
      neurodegenerative phase of MS.

PMID- 30231071
TI  - Euler's elastica and curvature based model for image restoration.
AB  - Minimization functionals related to Euler's elastica energy has a broad range of
      applications in computer vision and image processing. This paper proposes a novel
      Euler's elastica and curvature-based variational model for image restoration
      corrupted with multiplicative noise. It combines Euler's elastica curvature with
      a Weberized total variation (TV) regularization and gets a novel Euler's elastica
      energy and TV-based minimization functional. The combined approach in this
      variational model can preserve edges while reducing the blocky effect in smooth
      regions. The implicit gradient descent scheme is applied to efficiently finding
      the minimizer of the proposed functional. Experimental results demonstrate the
      effectiveness of the proposed model in visual improvement, as well as an increase
      in the peak signal-to-noise ratio, compared to the PDE-based methods.

PMID- 30231072
TI  - Changes in HIV prevention programme outcomes among key populations in Kenya: Data
      from periodic surveys.
AB  - The Kenya National AIDS and STI Control Programme (NASCOP) conducted annual
      polling booth surveys (PBS) in 2014 and 2015 to measure outcomes from the
      national HIV prevention programme for key populations (KPs), comprising
      behavioural, biomedical and structural interventions. KPs included female sex
      workers (FSWs), men who have sex with men (MSM) and people who inject drugs
      (PWID). We compared survey results from the first and second rounds. Comparing
      the second to the first round, significantly more FSWs (93% vs. 88%, p<0.001) and
      MSM (77% vs. 58%, p<0.001) reported condom use at last sex with a paying client,
      and at last anal sex among MSM (80% vs. 77%, p<0.05) and PWID (48% vs. 27%,
      p<0.01). However, condom use with regular partners remained low, at less than 53%
      for FSWs and 69% for MSM. Among PWID, there was a significant increase in use of
      new needles and syringes at last injection (93% vs. 88%, p<0.001), and a
      significant decrease in reported non-availability of clean needles (23% vs. 36%,
      p<0.001). The number of overdoses in the past six months reduced significantly
      but remained high (40% vs. 51%, p<0.001). FSWs and MSM reported significantly
      higher HIV testing, and in all KP groups, over 93% reported ever having been
      tested for HIV. Among the respondents self-reporting to have tested HIV positive
      (24% of FSW, 22% of MSM and 19% of PWID), 80% of FSWs, 70% of MSM, and 73% of
      PWID reported currently taking antiretroviral therapy (ART). While the experience
      of forced intercourse by partners declined among FSWs (18% vs. 22%, p<0.01) and
      MSM (13% vs. 17%, p<0.01), more FSWs reported violence by law enforcement
      personnel (49% vs. 44%, p<0.001). These findings provide valuable information on
      the programme's progress, and a signpost for the integrated behavioural,
      biomedical and structural interventions to achieve their HIV prevention targets.

PMID- 30231073
TI  - Shifts in ovine cardiopulmonary microRNA expression in late gestation and the
      perinatal period.
AB  - BACKGROUND: MicroRNAs (miRNAs) have been identified as important contributors to
      the regulation of early fetal cardiopulmonary development. However, miRNA
      expression profiles during late gestation and the early neonatal period are not
      fully elaborated in large mammals such as sheep (ovis aries). The aim of this
      study was to sequence miRNA from cardiopulmonary tissues in late gestation and
      neonate sheep to identify changes in miRNA expression. METHODS: Illumina HiSeq
      next-generation deep sequencing (NGS) was performed on ovine tissues from the
      left (LV) and right ventricles (RV), lungs and pulmonary artery (PA) of preterm
      fetuses (128 days), near-term fetuses (140 days) (term = 148 days) and neonatal
      lambs (5 days). NGS reads were mapped to the sheep genome (OviAri) and published
      miRNA sequences. RESULTS: Of 1345 cardiopulmonary miRNAs that were sequenced,
      relatively few major shifts in miRNA expression were detected with increased age
      from near term to neonates, and were confirmed by quantitative real-time PCR: bta
      miR-146a (lung), bta-miR-22-3p (lung, LV), hsa-miR-335* (lung, PA), and miR-210
      (lung, PA, LV). CONCLUSIONS: Sequencing of miRNA led to identification of four
      predominant miRNA in ovine cardiopulmonary tissues which alter expression during
      late gestation and the early neonatal period, concurrent with important
      functional changes in heart and lungs.

PMID- 30231074
TI  - Particulate metal exposures induce plasma metabolome changes in a commuter panel
      study.
AB  - INTRODUCTION: Advances in liquid chromatography-mass spectrometry (LC-MS) have
      enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for
      measuring environmental exposures and corresponding biological response. Using
      measurements collected as part of a large, panel-based study of car commuters,
      the current analysis examines in-vehicle air pollution concentrations, targeted
      inflammatory biomarker levels, and metabolomic profiles to trace potential
      metabolic perturbations associated with on-road traffic exposures. METHODS: A 60
      person panel of adults participated in a crossover study, where each participant
      conducted a highway commute and randomized to either a side-street commute or
      clinic exposure session. In addition to in-vehicle exposure characterizations,
      participants contributed pre- and post-exposure dried blood spots for 2-hr
      changes in targeted proinflammatory and vascular injury biomarkers and 10-hr
      changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS
      system in positive and negative electrospray ionization (ESI) mode. Data were
      processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features
      associated with environmental exposures or biological endpoints were identified
      with a linear mixed effects model and annotated through human metabolic pathway
      analysis in mummichog. RESULTS: HRM detected 10-hr perturbations in 110 features
      associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which
      reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two
      hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1beta were
      also associated with 10-hr changes in the plasma metabolome, suggesting diverse
      amino acid, leukotriene, and antioxidant metabolism effects. A putatively
      identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to
      particulate metals, suggesting a subclinical immune response. CONCLUSIONS: Acute
      exposures to traffic-related air pollutants are associated with broad
      inflammatory response, including several traditional markers of inflammation.

PMID- 30231075
TI  - ART initiation in an outpatient treatment center in Dakar, Senegal: A
      retrospective cohort analysis (1998-2015).
AB  - OBJECTIVE: To examine how patient characteristics combined with ART eligibility
      expansions affect the initiation of antiretroviral therapy (ART) among eligible
      patients attending a referral center in Senegal from 1998 to 2015. METHODS: This
      is a retrospective observational study carried out at the outpatient treatment
      Centre (Centre de Traitement Ambulatoire) in Dakar, Senegal, based on
      computerized medical records, gathered from 1998 to 2015, of ART-naive patients
      over 15 years of age. ART eligibility was defined as (CD4 count below 200) or as
      (WHO stage 4) or as (WHO stage 3 with (CD4 count below 350 or with unavailable
      CD4 count)) in 1998-2010; as (CD4 count below 350) or as (WHO stage 3 or 4) in
      2011-2013; as (CD4 count below 500) or as (WHO stage 3 or 4) in 2014-2015. Four
      periods were defined according to ART eligibility expansions and Senegal's HIV
      care history: 1998-2003 (P 1), 2004-2010 (P 2), 2011-2013 (P3), and 2014-2015
      (P4). Patients were expected to participate financially in their treatment during
      the first period (P1). RESULTS: A total of 3651 patient records were included.
      The median patient age was 40 years (IQR: 32-48). Women represented 56% of the
      population. The median CD4 count was 183 cells/mm3. Overall, 53% of patients had
      CD4 < 200 cells/mm3 at entry. This proportion reached 45% in 2014-2015. 2535
      patients (69%) were eligible for therapy, including 1503 (41%) who started ART.
      The proportion of treated patients among those who were eligible at entry or
      later increased steadily from 25%, 47%, 75% to 82% in the four periods,
      respectively. The median time to treatment decreased from 5.6 months (IQR: 3-11)
      in P1 to 0.8 months (IQR: 0-2) in P4. Eligible patients with more advanced
      disease (CD4<200 cells/mm3 and/or clinical stage 3 or 4) were more likely to be
      ART initiated than those with CD4>=200 cells/mm3 and/or clinical stage 1 or 2 at
      each stage of ART eligibility expansion. CONCLUSION: ART eligibility expansions
      were marked by a sharp increase in the proportion of eligible patients initiating
      treatment. These results show that in terms of management, the target of "Test
      and Treat" can be easily reached but that HIV testing will remain a key element
      to improve treatment success, as illustrated by the high proportion of people
      with advanced stage of infection at the time of ART initiation.

PMID- 30231076
TI  - Diagnostic accuracy of contrast-enhanced dynamic CT for small hypervascular
      hepatocellular carcinoma and assessment of dynamic enhancement patterns: Results
      of two-year follow-up using cone-beam CT hepatic arteriography.
AB  - OBJECTIVE: To evaluate the accuracy of CT for small, hypervascular hepatocellular
      carcinomas (HCCs) and assess the enhancement patterns on CT. MATERIALS AND
      METHODS: Ninety-nine patients who underwent cone-beam CT hepatic arteriography
      (CBCT-HA) during initial chemoembolization for HCC suspected on CT were enrolled
      in this study. A total of 297 hypervascular HCCs (142 >= 1 cm, 155 < 1 cm) were
      confirmed as HCCs based on two-year follow-up CT and CBCT-HA images. During the
      two-year follow-up, pre-existing hypervascular foci on CBCT-HA were regarded as
      HCCs at the initial presentation. Two radiologists categorized HCCs according to
      the following enhancement patterns on CT: type I, arterial enhancement and
      washout; type II, arterial enhancement without washout; and type III, no arterial
      enhancement. Two blinded reviewers rated the possibility of HCC. RESULTS: For the
      297 HCCs, the enhancement patterns according to size were as follows: type I >=1
      cm in 114 HCCs; type I <1 cm in 40 HCCs; type II >=1 cm in 16 HCCs; type II <1 cm
      in 37 HCCs; type III >=1 cm in 12 HCCs; and type III <1 cm in 10 HCCs. The
      remaining 68 HCCs (22.9%) were not detected on CT. The detection rates of HCCs >=
      1 cm were 83.1%, 76.8%, and 83.1% in the formal report for reviewer 1 and
      reviewer 2. In comparison, the detection rates of HCCs < 1 cm were 20.6%, 17.4%,
      and 17.4% in the formal report for reviewer 1 and reviewer 2. CONCLUSION: Many
      subcentimeter sized hypervascular HCCs were frequently missed or not evident on
      CT at the initial diagnostic workup. CT has limitations for diagnosing HCCs that
      are <1 cm in size or have atypical enhancement patterns.

PMID- 30231077
TI  - Multi-stage optimization of a deep model: A case study on ground motion modeling.
AB  - In this study, a multi-stage optimization procedure is proposed to develop deep
      neural network models which results in a powerful deep learning pipeline called
      intelligent deep learning (iDeepLe). The proposed pipeline is then evaluated by a
      challenging real-world problem, the modeling of the spectral acceleration
      experienced by a particle during earthquakes. This approach has three main stages
      to optimize the deep model topology, the hyper-parameters, and its performance,
      respectively. This pipeline optimizes the deep model via adaptive learning rate
      optimization algorithms for both accuracy and complexity in multiple stages,
      while simultaneously solving the unknown parameters of the regression model.
      Among the seven adaptive learning rate optimization algorithms, Nadam
      optimization algorithm has shown the best performance results in the current
      study. The proposed approach is shown to be a suitable tool to generate solid
      models for this complex real-world system. The results also show that the
      parallel pipeline of iDeepLe has the capacity to handle big data problems as
      well.

PMID- 30231078
TI  - Crystal structure of a soluble fragment of poliovirus 2CATPase.
AB  - Poliovirus (PV) 2CATPase is the most studied 2C protein in the Picornaviridae
      family. It is involved in RNA replication, encapsidation and uncoating and many
      inhibitors have been found that target PV 2CATPase. Despite numerous
      investigations to characterize its functions, a high-resolution structure of PV
      2C has not yet been determined. We report here the crystal structure of a soluble
      fragment of PV 2CATPase to 2.55A, containing an ATPase domain, a zinc finger and
      a C-terminal helical domain but missing the N-terminal domain. The ATPase domain
      shares the common structural features with EV71 2C and other Superfamily 3
      helicases. The C-terminal cysteine-rich motif folds into a CCCC type zinc finger
      in which four cysteine ligands and several auxiliary residues assist in zinc
      binding. By comparing with the known zinc finger fold groups, we found the zinc
      finger of 2C proteins belong to a new fold group, which we denote the
      "Enterovirus 2C-like" group. The C-terminus of PV 2CATPase forms an amphipathic
      helix that occupies a hydrophobic pocket located on an adjacent PV 2CATPase in
      the crystal lattice. The C-terminus mediated PV 2C-2C interaction promotes self
      oligomerization, most likely hexamerization, which is fundamental to the ATPase
      activity of 2C. The zinc finger is the most structurally diverse feature in 2C
      proteins. Available structural and virological data suggest that the zinc finger
      of 2C might confer the specificity of interaction with other proteins. We built a
      hexameric ring model of PV 2CATPase and visualized the previously identified
      functional motifs and drug-resistant sites, thus providing a structure framework
      for antiviral drug development.

PMID- 30231079
TI  - What's in a name? A naming convention for geomorphic river types using the River
      Styles Framework.
AB  - Meaningful iteration between place-based knowledge of rivers and generalised,
      theoretically-framed understandings is a significant challenge in river science
      and management. How can we communicate knowledge of the inherent complexity of
      river systems in light of managerial quests for simple, easy-to-apply frameworks
      that can be used by a wide range of practitioners, such that we can meaningfully
      transfer experiences in river science and management from one situation to
      another? Identification, definition, classification and naming are vital parts of
      this process. In a sense, a name is like a 'brand', for which a consistency of
      product is expected. The River Styles Framework is a flexible, open-ended
      approach to river science and management. The Framework applies a set of
      hierarchical principles to differentiate reaches, interpret their process-based
      behaviour and examine interactions between patterns of reaches at the catchment
      scale. Here we outline an evolution and tightening of the Framework to better
      communicate how to identify and name types of river at the reach scale. Like the
      River Styles Framework itself, the naming convention applies hierarchical
      procedures, starting at the valley setting scale, and incorporating analyses of
      river planform, channel and floodplain landforms (geomorphic units) and bed
      material texture. Using a series of examples from around the world, we show how
      this naming convention can be applied to name river reaches and can be adapted to
      particular purposes in a consistent, readily communicable manner. We outline
      various challenges that are faced in managing the use of such a naming
      convention.

PMID- 30231080
TI  - Role of p53 and transcription-independent p53-induced apoptosis in shear
      stimulated megakaryocytic maturation, particle generation, and platelet
      biogenesis.
AB  - Megakaryocytes (Mks) derive from hematopoietic stem and progenitor cells (HSPCs)
      in the bone marrow and develop into large, polyploid cells that eventually give
      rise to platelets. As Mks mature, they migrate from the bone marrow niche into
      the vasculature, where they are exposed to shear forces from blood flow,
      releasing Mk particles (platelet-like particles (PLPs), pro/preplatelets (PPTs),
      and Mk microparticles (MkMPs)) into circulation. We have previously shown that
      transcription factor p53 is important in Mk maturation, and that physiological
      levels of shear promote Mk particle generation and platelet biogenesis. Here we
      examine the role of p53 in the Mk shear-stress response. We show that p53 is
      acetylated in response to shear in both immature and mature Mks, and that
      decreased expression of deacetylase HDAC1, and increased expression of the
      acetyltransferases p300 and PCAF might be responsible for these changes. We also
      examined the hypothesis that p53 might be involved in the shear-induced Caspase 3
      activation, phosphatidylserine (PS) externalization, and increased biogenesis of
      PLPs, PPTs, and MkMPs. We show that p53 is involved in all these shear-induced
      processes. We show that in response to shear, acetyl-p53 binds Bax, cytochrome c
      is released from mitochondria, and Caspase 9 is activated. We also show that
      shear-stimulated Caspase 9 activation and Mk particle biogenesis depend on
      transcription-independent p53-induced apoptosis (TIPA), but PS externalization is
      not. This is the first report to show that shear flow stimulates TIPA and that
      Caspase 9 activation and Mk-particle biogenesis are directly modulated by TIPA.

PMID- 30231082
TI  - A Novel Experimental Dental Implant Permits Quantitative Grading of Surface
      Property Effects on Osseointegration.
AB  - PURPOSE: To test the hypothesis if a novel single-chamber experimental dental
      implant allows in vivo the quantitative assessment of osseointegration over time
      and as a function of different surface properties (physical, chemical, geometric,
      biologic [osteoconductive or osteoinductive]) in a biologically unfavorable
      environment (local osteoporosis). MATERIALS AND METHODS: Three prototypes of a
      novel experimental implant with different chamber sizes (small, medium, and
      large) were compared with each other to find out the minimum size of bone
      chambers needed to allow a discriminative quantification of osseointegration over
      time. For the comparison of low and high surface osteoconductivity properties,
      conventional sandblasted, acid-etched chamber surfaces (low surface
      osteoconductivity) were compared with biomimetically (calcium phosphate) coated
      ones (high surface osteoconductivity). The implants (4 implants per animal; 88
      implants per time point) were inserted into the edentulous maxillae of a total of
      66 adult goats with a physiologically osteoporotic masticatory apparatus. Two, 4,
      and 8 weeks later, they were excised and prepared for a histomorphometric
      analysis of the volume of neoformed bone within the chamber space and of the bone
      to-implant contact (BIC) area. RESULTS: The implants with small chambers did not
      show significant differences in bone coverage (BIC) nor bone volume (relative and
      absolute volume), neither as a function of time nor as of implant surface
      property (low versus high surface osteoconductivity). However, medium and large
      chambers revealed significant differences respecting both of these parameters
      over the 8-week postoperative time period. CONCLUSION: The new implant model
      permits a discriminative quantification of osseointegration in vivo in an
      osteoporotic bone environment for implants with medium-sized and large-sized
      chambers. Quantitative assessment of osseointegration is possible, both over time
      and as a function of low and high surface osteoconductivity properties.

PMID- 30231081
TI  - Impact of repeated anesthesia with ketamine and xylazine on the well-being of
      C57BL/6JRj mice.
AB  - Within the scope of the 3Rs of Russel and Burch, the number of laboratory animals
      can be reduced by repeated use of an animal. This strategy only becomes relevant,
      if the total amount of pain, distress or harm the individual animal experiences
      does not exceed the severity of a single manipulation. For example, when using
      imaging techniques, an animal can be examined several times during a study, but
      it has to be anesthetized each time imaging is performed. The severity of
      anesthesia is thought to be mild according to the Directive 2010/63/EU. However,
      the Directive does not differentiate between single and repeated anesthesia,
      although repeated anesthesia may have a greater impact on well-being. Hence, we
      compared the impact of single and repeated anesthesia (six times at an interval
      of three to four days) by injection of ketamine and xylazine (KX) on the well
      being of adult female and male C57BL/6JRj mice. After anesthesia, well-being of
      mice was assessed according to a protocol for systematic assessment of well-being
      including nesting, the Mouse Grimace Scale (MGS), a test for trait anxiety, home
      cage activity, and the rotarod test for motor activity, food intake, and body
      weight, as well as corticosterone (metabolite) analysis. Repeated anesthesia
      increased the MGS in mice of both sexes and caused short-term effects on well
      being of female mice in the immediate post-anesthetic period, indicated by longer
      lasting effects on trait anxiety-related behavior. However, corticosterone
      metabolite concentrations suggested that mice habituated to the stress induced by
      repeated KX administration. Hence, the mildly negative effects on well-being of
      repeated KX anesthesia do not seem to accumulate over time using the respective
      regimen. However, further observations for severity classification are warranted
      in order to more specifically determine the duration of mild distress and trait
      anxiety.

PMID- 30231083
TI  - Systematic Review and Meta-Analysis of Hard Tissue Outcomes of Alveolar Ridge
      Preservation.
AB  - PURPOSE: Alveolar ridge preservation procedures have been advocated to minimize
      postextraction dimensional loss. There is a need for systematic analyses of
      clinical factors affecting the outcomes of these procedures in order to improve
      their clinical outcomes. This systematic review and meta-analysis aimed to assess
      the efficacy of alveolar ridge preservation procedures in terms of hard tissue
      dimensional changes and to determine clinical factors affecting outcomes of these
      procedures. MATERIALS AND METHODS: Studies comparing alveolar ridge preservation
      procedures with tooth extraction alone that reported quantitative outcomes for
      hard tissue dimensional changes were included. The primary outcome variable was
      horizontal dimensional changes of alveolar bone. Subgroup analyses evaluated
      effects of wound closure, flap elevation, type of grafting materials, use of
      barrier membranes, use of growth factors, socket morphology, and the position of
      teeth on outcomes of alveolar ridge preservation procedures. RESULTS: Twenty-one
      studies were included, and quantitative analyses were performed for seven outcome
      variables. Significant differences between alveolar ridge preservation and
      control sites were found for six outcome variables, all favoring alveolar ridge
      preservation procedures. The magnitude of effect for the primary outcome variable
      (horizontal dimensional changes of alveolar bone) was 1.86 mm (95% CI = 1.44,
      2.28; P < .001). This magnitude of effect for the primary variable (as determined
      by subgroup analysis) was also significantly affected by type of wound closure (P
      = .033), type of grafting materials (P = .001), use of barrier membranes (P =
      .006), use of growth factors (P = .003), and socket morphology (P < .001).
      CONCLUSION: Alveolar ridge preservation procedures are effective in minimizing
      postextraction hard tissue dimensional loss. The outcomes of these procedures are
      affected by morphology of extraction sockets, type of wound closure, type of
      grafting materials, use of barrier membranes, and use of growth factors.

PMID- 30231084
TI  - Intrasinus Bone Gain with the Osteotome Sinus Floor Elevation Technique: A Review
      of the Literature.
AB  - PURPOSE: To evaluate the mean amount of intrasinus bone obtainable with the
      osteotome technique for transcrestal maxillary sinus elevation combined with
      simultaneous implant insertion, with and without the use of grafting materials.
      MATERIALS AND METHODS: A review was conducted on PubMed, Scopus, and Cochrane
      central databases. Only human studies in which implant placement was contextual
      to the sinus elevation procedure, without additional crestal regenerative
      procedures and with a minimum 1-year follow-up, were selected. Seventeen studies
      were found to meet the selection criteria. RESULTS: No statistically significant
      difference between the two procedures was detected. The mean intrasinus bone gain
      at 3 years after surgery was 2.99 mm in cases where no grafting material was used
      and 4.24 mm in cases in which grafting materials were used. The mean percentage
      of crestal height increase at the implant site at 3 years after surgery,
      referring to a selection of studies with initial bone height > 4 mm, was 47.28%
      in procedures without grafting material and 62.68% in procedures with grafting
      material. A different dimensional behavior of the newly formed bone during the
      first 3 years after surgery was found: a slight volumetric shrinkage in grafting
      procedures and a slight bone increase in procedures without grafting material. No
      statistically significant difference in implant survival rate was found.
      CONCLUSION: Both osteotome transcrestal sinus elevation procedures seem to
      guarantee predictable short- and medium-term results with reference to the
      intrasinus bone gain. However, the use of grafting materials, compared with their
      nonuse, does not seem to have substantial advantages in the short and medium term
      as far as mean intrasinus bone gain is concerned.

PMID- 30231085
TI  - Enhancement of Bone Augmentation in Osteoporotic Conditions by the Intermittent
      Parathyroid Hormone: An Animal Study in the Calvarium of Ovariectomized Rat.
AB  - PURPOSE: Intermittent parathyroid hormone (PTH) is the commonly used therapeutic
      approach for patients with severe osteoporosis. The goal of this study was to
      elucidate the effect of the intermittent PTH treatment on guided bone
      augmentation (GBA) in the calvarium of ovariectomized (OVX) rats. MATERIALS AND
      METHODS: Surgical ovariectomy on 14 rats and sham surgery on 7 rats were
      conducted on all rats as the first surgery. GBA surgery was conducted 8 weeks
      following the first surgery in the rat calvarium by placing 5-mm-diameter
      cylindrical plastic caps. Following surgery, rats were treated with 40 MUg/kg PTH
      (OVX-PTH) or saline (Sham-Saline, OVX-Saline) via intraperitoneal injection three
      times per week during the all-observational period. Longitudinal microcomputed
      tomography (micro-CT) imaging was performed every 2 weeks following the GBA
      surgery without euthanasia, and the amount of newly generated bone volume (BV)
      was calculated. All rats were euthanized 12 weeks after GBA surgery, and
      histology was obtained. Sections stained with hematoxylin and eosin were used for
      the quantitative analysis of newly generated tissue, and immunohistology was used
      to visualize Runx2-positive cells and TRAP-positive cells. RESULTS: Throughout
      the monitoring period, the BVs of OVX rats without PTH treatment (OVX-Saline)
      were significantly lower than that of the other two groups at weeks 8 and 12 in
      micro-CT analysis. During all experimental periods, the BV was highest in the OVX
      rats that were treated with PTH (OVX-PTH). Histologic analysis confirmed the
      result of micro-CT, and determined that the OVX-PTH presented a greater number of
      Runx2-positive cells. The number of TRAP-positive multinucleated osteoclasts was
      highest in OVX-PTH rats; there were no significant differences between the other
      two groups. CONCLUSION: The results of this study suggest that treatment with
      intermittent PTH was associated with increased newly regenerated bone volume in
      ovariectomized rat calvarial bone augmentation, which may have important clinical
      implications.

PMID- 30231086
TI  - Effect of Plasma Oxidation-Treated TiOx Film on Early Osseointegration.
AB  - PURPOSE: To develop a TiOx film with high wettability using plasma oxidation
      methodology and to evaluate the effect of such surface modification on new bone
      formation and early osseointegration. MATERIALS AND METHODS: Twenty sandblasted
      and acid-etched (SLA) titanium implants layered with a TiOx film layer were
      modified by plasma oxidation using a Radio Frequency Plasma Enhanced Chemical
      Vapor Deposition (RFPECVD) system. Twenty SLA implants without any treatment were
      employed as the control group. Scanning electron microscopy was used to evaluate
      surface morphology of the coating. X-ray photoelectron spectroscopy (XPS) was
      utilized to identify the chemical composition of the implant surface, and the
      wettability was tested with the help of the contact angle calculation. All
      implants were randomly inserted into the proximal tibia of 20 rats with a split
      plot design. Four weeks after implantation, early osseointegration of the two
      groups was analyzed by a removal torque test and histologic analysis. RESULTS:
      The surface characteristics showed that both SLA and plasma oxidization-treated
      SLA (PO-SLA) surfaces displayed similar typical isotropic irregular indentations.
      As revealed by the XPS analyses, both TiO2 and Ti2O3 were coexistent in the PO
      SLA surface. The contact angle measurement revealed that the super-hydrophilic
      surface was created out in the PO-SLA surface. Four weeks after implantation, a
      higher removal torque value was observed in the group of implants with the PO-SLA
      surface compared with the control group (12.68 +/- 1.07 vs 9.95 +/- 1.42 Ncm, P <
      .05), and a higher rate of bone-to-implant contact was also detected in the same
      group of implants with the PO-SLA surface (47.79% +/- 9.59% vs 39.41% +/- 9.00%,
      P < .05). The bone area ratio was also higher in the PO-SLA surface group than
      the control group (39.10% +/- 10.01% vs 29.01% +/- 7.24%, P < .05). CONCLUSION:
      It was indicated that the PO-SLA surface has combined the effect of high
      wettability and micro/nano-structures to notably increase early bone apposition.

PMID- 30231087
TI  - Microstructural Evaluation of Contaminated Implant Surface Treated by Laser,
      Photodynamic Therapy, and Chlorhexidine 2 percent.
AB  - PURPOSE: Decontamination of the rough surfaces of dental implants is a challenge
      in the treatment of peri-implantitis. An acceptable cleaning technique must be
      able to debride and detoxify the surface without traumatizing it. This study
      assessed the possible implant surface alterations following decontamination with
      laser, photodynamic therapy (PDT), and application of chlorhexidine (CHX).
      MATERIALS AND METHODS: Of 16 dental implants with sandblasted, large-grit, acid
      etched surfaces, Aggregatibacter actinomycetemcomitans was cultured on the
      surfaces of 15 implants for 48 hours. These 15 implants were divided into five
      groups of three and were subjected to erbium-doped yttrium aluminum garnet
      (Er:YAG) laser irradiation, 630 nm light-emitting diode and toluidine blue O
      photosensitizer, 810 nm diode laser, and indocyanine green-based photosensitizer,
      2% CHX, and control group (no treatment). One implant remained intact. The
      morphology and element/phase identification of the implants were studied using
      scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy
      (EDS), respectively. RESULTS: The SEM images and EDS maps revealed that the
      decontamination methods did not alter the surface quality of the implants.
      However, in photodynamic therapy, sodium chloride that remained from rinsing
      liquid can make an adhesive layer on the surface of the treated implants.
      CONCLUSION: Er:YAG laser irradiation and PDT did not alter the surfaces of
      sandblasted, large-grit, acid-etched implants.

PMID- 30231088
TI  - Evaluation of Vertical Misfit of CAD/CAM Implant-Supported Titanium and Zirconia
      Frameworks.
AB  - PURPOSE: This study compared the vertical misfit of fixed implant-supported
      titanium (Ti6Al4V) and yttria-stabilized tetragonal zirconia frameworks milled
      using the computer-aided design/computer-aided manufacturing (CAD/CAM) Zirkonzahn
      system. MATERIALS AND METHODS: An aluminum mandibular master cast was used, and
      four analogs of the Regular CrossFit implant for straight multibase titanium
      alloy abutments (Institut Straumann) were fixed with self-curing acrylic resin in
      mandibular canine and second premolar tooth locations with the aid of a
      parallelometer. Scan abutments were placed over the four straight multibase
      Regular CrossFit abutments to determine their correct three-dimensional (3D)
      positioning in the virtual model. Implant frameworks were designed virtually, and
      five frameworks of each material (titanium alloy or yttria-stabilized tetragonal
      zirconia) were milled using the CAD/CAM system. Scanning electron microscope
      (SEM) images, with magnifications of 50*, 250*, and 1,000*, were obtained from
      three points on the buccal surface, three points on the lingual surface, and
      three points on the mesial surface of each abutment. The measurements were
      performed in the center of each of the thirds, thus defining points one, two, and
      three. The degree of vertical misfit at the framework-abutment interface was
      determined using ImageJ software and analyzed using the Student t test (P = .05).
      RESULTS: The mean misalignment value was 6.011 +/- 0.750 MUm for the titanium
      group and 9.055 +/- 3.692 MUm for the zirconia group. CONCLUSION: Within the
      limitations of this study, there was no significant difference in vertical misfit
      between the titanium and zirconia implant frameworks produced using the CAD/CAM
      system. Regardless of the material used, the CAD/CAM frameworks achieved an
      adequate vertical fit.

PMID- 30231089
TI  - Control Variable Implants Improve Interpretation of Surface Modification and
      Implant Design Effects on Early Bone Responses: An In Vivo Study.
AB  - PURPOSE: This in vivo study used control variable implants to compare early bone
      responses in fluoride-modified (F-mod) and hydrophilic, sandblasted, large-grit,
      acid-etched (modSLA) surface implants that differed in implant design. MATERIALS
      AND METHODS: Four different types of implants (n = 24) were prepared: F-mod
      surface with Astra Tech implant design; modSLA surface with Straumann implant
      design; sandblasted, large-grit, acid-etched (SLA) surface with Astra Tech
      design; and SLA surface with Straumann implant design. Scanning electron
      microscopy, confocal laser scanning microscopy, and x-ray photoelectron
      spectroscopy were performed to assess implant surface characteristics. Four
      implants from each implant type were inserted in the tibiae of four rabbits that
      were sacrificed 10 days after surgery. Bone-to-implant contact (BIC) and bone
      area (BA) were measured to evaluate early bone responses. Analysis of variance
      with Tukey's multiple comparison method was used for the histomorphometric data
      to find any significant difference. The surface characteristic-related data were
      analyzed using the Kruskal-Wallis test. The level of significance was .05 in
      statistical analyses. RESULTS: No significant differences in BIC and BA were
      found among the modified surfaces (P > .05), whereas significant differences were
      found in surface topography and surface chemistry. The different designs showed
      no significant effects on early bone responses when identical surface
      modifications were applied (P > .05). CONCLUSION: F-mod and modSLA surfaces
      showed no significant differences in early bone responses. Furthermore, the
      implant design had no influence on the bone response. This in vivo experimental
      model will help improve the evaluation of surface modification factors by
      allowing an independent estimation of one variable (surface modification) against
      a constant (implant design).

PMID- 30231090
TI  - Debonding Forces for Two-Piece Zirconia Abutments with Implant Platforms of
      Different Diameter and Use of Different Luting Strategies.
AB  - PURPOSE: The forces needed to detach zirconia copings from titanium inserts of
      two-piece abutments were evaluated for implant platforms of different diameters
      (4.8 and 6.5 mm) and different luting strategies. MATERIALS AND METHODS: Eight
      specimens (four for each platform diameter) were prepared to simulate two-piece
      zirconia implant abutments with prefabricated titanium inserts and computer-aided
      design/computer-aided manufactured (CAD/CAM) zirconia copings. Half of the
      copings were luted to their titanium inserts by use of composite cement; the
      others were luted after additional bonding treatment of the titanium and zirconia
      surfaces. All specimens were subjected to tensile forces up to failure. Samples
      were used with or without artificial aging. Each specimen was luted and
      subsequently debonded 12 times; thus, a total of 96 tests were conducted.
      RESULTS: All debonding forces exceeded approximately 600 N. Larger platform
      diameters (P < .001) and additional bonding treatment (P = .021) resulted in
      significantly better retention; artificial aging had no effect (P = .165).
      CONCLUSION: Forces for debonding of titanium bases from zirconia abutments were
      favorable. The use of these abutments might be a viable prosthetic treatment
      option in specific clinical cases.

PMID- 30231091
TI  - Recombinant Human Platelet-Derived Growth Factor-BB in Human Alveolar Ridge
      Augmentation: A Review of the Literature.
AB  - PURPOSE: The objective of this study was to review the available literature
      regarding the use of recombinant human platelet-derived growth factor-BB (rhPDGF
      BB) in human alveolar ridge augmentation and to assess its effectiveness for this
      specific use. MATERIALS AND METHODS: Three electronic searches of the MEDLINE
      database were performed. RESULTS: This review noted a wide range of study
      protocols, carrier systems, study periods, and outcome measures. CONCLUSION:
      Within the limits of this literature review, the use of rhPDGF-BB and bone
      regeneration/ridge augmentation led to greater clinical attachment level gain and
      bone regeneration prior to implant placement. More controlled clinical studies
      are needed to establish the effectiveness of rhPDGF-BB in alveolar ridge
      augmentation.

PMID- 30231092
TI  - Vertical Bone Augmentation Using Ring Technique with Three Different Materials in
      the Sheep Mandible Bone.
AB  - PURPOSE: The purpose of this study was to examine the volumetric alterations and
      osseointegration properties in the augmented area of the ring technique using
      different types of bone graft material in sheep mandible bone. MATERIALS AND
      METHODS: Three different materials (columnar forms, 7-mm diameter, 3-mm height)
      were stabilized using dental implants with a turned surface in the mandible bone
      of Finnish Dorset cross-bred sheep: group A, autogenous bone; group B, bovine
      bone; group C, biphasic bone substitute. Animals were euthanized after 5 weeks (N
      = 6). Three-dimensional image data by digital oral scanner were taken at the
      surgery and sacrifice, and the volume alteration of the material was calculated.
      The bone samples were fixed in formalin and dehydrated in ethanol. Resin-embedded
      samples were subjected to non-decalcified ground sectioning, and histologic and
      histomorphometric analysis (bone and material area alteration, bone-to-implant
      contact [BIC]) were done. RESULTS: In three-dimensional (3D) image analysis,
      group A showed a statistically higher percentage of remaining materials compared
      with groups B and C. The histologic observation showed no new bone formations
      around the implants in all groups, especially at the maxillary site of the
      implant in the augmented area. In histomorphometric analysis, group A showed a
      statistically higher percentage of bone area (BA) compared with groups B and C;
      however, in all groups, bone-to-implant contact (BIC) showed low values, and
      there were no statistical differences between groups. CONCLUSION: The results of
      this study suggested that the autogenous bone maintained bone volume around the
      dental implant using the ring technique, and the impact of surface properties was
      of some importance; osseointegration with the turned surface in the augmented
      area showed low BIC values in all groups.

PMID- 30231093
TI  - Marginal Adaptation of Provisional CAD/CAM Restorations Fabricated Using Various
      Simulated Digital Cement Space Settings.
AB  - PURPOSE: The ideal digital cement space value for the fabrication of provisional
      computer-aided design/computer-aided manufacturing (CAD/CAM) crowns with
      clinically acceptable marginal adaptation is not well known. The aim of this
      study was to evaluate the effect of different simulated cement space settings on
      the marginal fit of poly(methyl methacrylate) (PMMA) provisional CAD/CAM
      restorations. MATERIALS AND METHODS: An extracted premolar tooth was prepared
      using ceramic crown preparation guidelines and represented both natural teeth
      and/or custom implant abutments. The prepared tooth abutment was scanned with a
      three-dimensional (3D) laboratory scanner (D900, 3Shape). CAD design software was
      used to subsequently design a premolar crown core with three different simulated
      cement space settings (20 to 40 MUm, 20 to 50 MUm, 20 to 60 MUm). PMMA blocks
      were used to mill the specimens (n = 9, N = 27). Using a stereo zoom microscope,
      a total of 36 images for each of the 3 groups (9 crowns per group, 4 sites per
      crown) were captured to measure the mean vertical marginal discrepancy for every
      group. One-way analysis of variance (ANOVA) was used to analyze the data, and the
      post hoc Tukey multiple comparison test was performed. RESULTS: The marginal gap
      values of the PMMA cores fabricated using the three cement space settings were
      significantly different from each other (P < .001). The marginal gap was smaller
      with a 20- to 60-MUm setting compared with 20 to 50 MUm and 20 to 40 MUm, and the
      20- to 50-MUm setting allowed for smaller marginal gaps compared with 20 to 40
      MUm (P < .001). CONCLUSION: Within the limitations of this study, the marginal
      gaps of CAD/CAM-fabricated PMMA cores were smaller when the cement space was
      larger. The smallest marginal gaps were achieved when a 20- to 60-MUm cement
      space was used (P < .001).

PMID- 30231095
TI  - Retentive Properties of Two Stud Attachments with Polyetherketoneketone or Nylon
      Insert in Mandibular Implant Overdentures.
AB  - PURPOSE: The aim of this study was to compare the retentive properties of an
      attachment with a nylon insert and an attachment with a polyetherketoneketone
      (PEKK) insert on two-implant mandibular overdentures during simulated masticatory
      loadings and insertion/removal cycles. MATERIALS AND METHODS: Two attachment
      systems with nylon inserts or PEKK inserts were investigated, including
      nylon/low, nylon/medium, nylon/high, PEKK/x-low, PEKK/low, PEKK/medium, and
      PEKK/high. The canine region of edentulous mandibular overdenture models was
      retained with two implant analogs through two different stud attachments at
      interimplant angulations of 0 and 20 degrees. The simulated mastication and
      insertion/removal cycles were 400,000 cyclic loadings and 1,080 times of
      insertion/removal. Wear patterns and deformations on the attachment surface were
      analyzed with scanning electron microscopy. RESULTS: At 0 and 20 degrees, initial
      retentive force was highest in nylon/high and lowest in PEKK/x-low. Final
      retentive force was highest in PEKK/high and PEKK/medium at 0 and 20 degrees,
      respectively, and PEKK/x-low was lowest at both angulations. At 0 degrees,
      nylon/low, nylon/medium, PEKK/x-low, and PEKK/low displayed a significant
      increase in retention (P < .05), and nylon/high and PEKK/medium showed a
      significant decrease in retention (P < .05), except PEKK/high, which exhibited no
      significant decrease (P > .05). At 20 degrees, nylon/low and PEKK/x-low increased
      retention significantly (P < .05), and nylon/medium, nylon/high, PEKK/low,
      PEKK/medium, and PEKK/high decreased retention significantly (P < .05). Patrices
      of both attachment systems barely showed detectable abrasion, while matrices
      revealed severe wear and surface deformation. Nylon inserts particularly
      displayed more noticeable wear and deformation than PEKK inserts. CONCLUSION:
      Within the limitations of this investigation, the attachment system with a PEKK
      insert indicated less abrasion and retention change than the attachment system
      with a nylon insert on both paralleled implants and axially tilted implants under
      400,000 cyclic loadings and 1,080 insertion/removal cycles for 1 year.

PMID- 30231094
TI  - Influences of Implant and Framework Materials on Stress Distribution: A Three
      Dimensional Finite Element Analysis Study.
AB  - PURPOSE: The aim of this study was to analyze and compare the stress distribution
      patterns of different implant and restorative materials in the supporting tissue
      and implants. MATERIALS AND METHODS: Twelve different implant/bone models were
      created using SolidWorks 2015 software (SolidWorks Corp) and analyzed using the
      finite element method. Straumann Bone Level implants with zirconia abutments and
      single-piece Straumann PURE Ceramic implants (Institute Straumann) restored with
      lithium disilicate glass-ceramic and zirconia ceramic cement-retained crowns were
      evaluated. A 118.2-N load was applied to the coronal aspect of the buccal cusp at
      a 75.8-degree angle in relation to the occlusal plane. Principal stress values
      for cortical and trabecular bone and the equivalent von Mises stress values for
      implants and frameworks were calculated. RESULTS: Zirconia (ZrO2) implant models
      showed lower principal stress values than the commercially pure titanium (cpTi)
      and titanium-zirconium (TiZr) implant models in cortical bone. All models showed
      similar principal stress values in trabecular bone. Von Mises stress values at
      the cpTi and TiZr implants were similar; however, values observed of ZrO2
      implants were higher. TiZr implants of 3.3 mm diameter showed similar strength to
      4.1-mm-diameter cpTi implants. Both zirconia and lithium disilicate glass-ceramic
      frameworks transferred similar von Mises stress values in the supporting tissue
      of implant-supported prostheses. CONCLUSION: Narrow-diameter TiZr implants may be
      preferred for patients who have insufficient bone volume without bone
      augmentation procedures due to the material's enhanced biomechanical properties.
      ZrO2 implants may be a suitable alternative for esthetic regions. Further
      clinical studies are recommended to investigate the long-term performance of TiZr
      and ZrO2 implants.

PMID- 30231096
TI  - Prevention and the Management of Complications Using the Zygoma Implant: A Review
      and Clinical Experiences.
AB  - PURPOSE: To review potential complications that may occur using the zygoma
      implant published in the literature as well as complications encountered by the
      primary author. Solutions for prevention as well as the management of such
      complications are also discussed in detail. MATERIALS AND METHODS: The authors
      have reviewed and outlined reports discussing the etiology as well as the
      management of potential complications associated with the use of the zygoma
      implant and have offered recommendations for the management of these
      complications. RESULTS: Predictable clinical solutions are offered for the
      identification of the cause as well as the management of complications, including
      orbital involvement, intracranial involvement, paresthesia of V2, subperiosteal
      infections, overextended apical extension, vestibular dehiscence, failed zygoma
      implant, fractured implant, and management of sinus infections. CONCLUSION: A
      comprehensive knowledge of the specific steps for the proper execution of this
      complex procedure will allow for a predictable outcome as presented by the
      systematic reviews of the zygoma implant, which have reported a cumulative
      survival rate of 96.7% to 97.8%. Understanding the cause, the prevention, as well
      as the management of potential complications is imperative for the contemporary
      surgeon using the zygoma implant.

PMID- 30231097
TI  - Effect of Photofunctionalization on Early Implant Failure.
AB  - PURPOSE: This study retrospectively evaluated the effects of bone density,
      staging strategy, implant stability, healing process, implant length, surface
      type, and photofunctionalization on early implant failure. MATERIALS AND METHODS:
      Consecutive study samples at Yokohama City University Hospital were analyzed for
      their early implant failure potentially influenced by patient-, surgical protocol
      , and implant-related factors. Through the screening process using univariate
      analysis for those factors, candidate influential factors such as bone density,
      staging strategy, the level of initial implant stability, postoperative wound
      breakdown, the length of implants, the surface type of implants, and use or
      nonuse of photofunctionalization were selected as independent variables in
      forward multivariate logistic regression analysis. The odds ratio (OR) for
      candidate factors was calculated. RESULTS: A total of 563 implants placed in 219
      patients from 2005 to 2017 were analyzed for their early implant failure.
      Stepwise logistic regression analysis finally identified postoperative wound
      breakdown (OR = 0.21) and the use of photofunctionalization (OR = 0.30) that
      significantly reduced the risk of early implant failure (P < .01 and P < .05,
      respectively). The implant failure rate was 10.0% with postoperative wound
      breakdown and 1.0% without it, whereas it was 4.3% without photofunctionalization
      and 1.3% with it. CONCLUSION: Among various patient-, surgical protocol-, and
      implant-related factors, the absence of postoperative wound breakdown and use of
      photofunctionalization significantly reduced the risk of early implant failure.
      It was notable that photofunctionalization, a unique, chairside measure to
      improve implant surfaces, was effective exclusively among implant-related
      factors.

PMID- 30231098
TI  - Clinical and Radiographic Evaluation of Bar, Telescopic, and Locator Attachments
      for Implant-Stabilized Overdentures in Patients with Mandibular Atrophied Ridges:
      A Randomized Controlled Clinical Trial.
AB  - PURPOSE: The aim of this study was to evaluate the clinical and radiographic peri
      implant tissues of bar, Locator, and resilient telescopic attachments for two
      implant stabilized overdentures in subjects with mandibular atrophied ridges.
      MATERIALS AND METHODS: Ninety edentulous individuals with mandibular ridge
      atrophy were randomly assigned into three equal groups and received two implants
      in the canine areas. Mandibular overdentures were constructed and attached to
      implants with Dolder bar attachments (BOD), resilient telescopes (TOD), and
      Locators (LOD). Plaque scores, gingival scores, pocket depths, implant stability,
      width of keratinized mucosa, vertical bone loss, and horizontal bone loss were
      evaluated at the time of prosthesis delivery and 6 months and 12 months after
      delivery. RESULTS: With the exception of pocket depth and implant stability, all
      parameters showed a significant increase from prosthesis delivery to 6 months.
      BOD recorded the highest plaque scores, gingival scores, and pocket depths
      followed by LOD, and TOD recorded the lowest values. No significant difference in
      implant stability and keratinized mucosa was observed between groups. TOD and BOD
      recorded the highest vertical and horizontal bone losses, respectively. LOD
      recorded the lowest vertical and horizontal bone losses. There was no difference
      in implant survival rate between groups. CONCLUSION: Bar, resilient telescopic,
      and Locator attachments can be used successfully for two-implant stabilized
      overdentures in subjects with mandibular atrophied ridges after a 1-year follow
      up period. Telescopic attachments were associated with improved clinical peri
      implant soft tissues compared with other attachments. However, Locator
      attachments may be advantageous in terms of peri-implant bone preservation.

PMID- 30231099
TI  - Facial Fenestration and Dehiscence Defects Associated With Immediate Implant
      Placement Without Flap Elevation in Anterior Maxillary Ridge: A Preliminary Cone
      Beam Computed Tomography Study.
AB  - PURPOSE: To examine cone beam computed tomography (CBCT) anatomical findings,
      such as the concavity of the ridge and angulation of the tooth and alveolar
      ridge, either facial or palatal, in order to assess the potential clinical risks
      of performing flapless implant surgery. MATERIALS AND METHODS: CBCT images that
      met the inclusion criteria were examined. All images in maxillary anterior areas
      (canine to canine), facial bone thickness at 3 and 5 mm from the cementoenamel
      junction (CEJ), angulation of the tooth and alveolar ridge (Angle T: the
      angulation between the long axis of the tooth and the palatal plane; Angle D: the
      angulation between the long axis of the tooth and the midline of the ridge), the
      deepest point of facial concavity, the distance from the deepest point of facial
      concavity to the apex of the tooth and alveolar bone crest, nasopalatine canal,
      dehiscence, and fenestrations were measured and statistically analyzed. RESULTS:
      In total, 21 patients (12 women and 9 men) with a mean age of 55.9 years who met
      the inclusion criteria were included in the analysis. Data from 21 patients, 6
      image sections per patient (total of 126 CBCT images) were analyzed. The mean
      value of facial bone thickness was 0.99 mm and 0.60 mm at 3 and 5 mm from CEJ,
      respectively. The distance from the deepest point of facial concavity to the apex
      of the tooth and alveolar bone crest was 2.79 and 11.29 mm, respectively. In
      canine areas, the mean values of facial bone thickness were larger at 3 mm but
      thinner at 5 mm. Also, canines were found to have a larger Angle D and a higher
      incidence of fenestration and dehiscence. CONCLUSION: Based on the findings,
      fenestration and a larger Angle D were associated with thinner facial bone
      thickness at 5 mm, and the tooth types also had an impact. Hence, for immediate
      implant surgery without flap elevation, besides anatomical structures, both
      angulation of the tooth and the alveolar ridge also need to be assessed.

PMID- 30231100
TI  - Peri-implant Bone Loss of Tissue-Level and Bone-Level Implants in the Esthetic
      Zone with Gingival Biotype Analysis.
AB  - PURPOSE: The esthetic outcome of dental implants can be compromised when some
      degree of bone loss occurs around the implant. This may particularly affect the
      tissue-level (TL) design. Therefore, bone-level (BL) design implants may be
      preferable if a natural emergence profile is important. Notwithstanding the
      implant design, the gingival biotype has been identified as a crucial factor in
      the stability of crestal bone. The objective of this study was to investigate
      bone loss in patients with different gingival biotypes at TL and BL implant sites
      in the esthetic zone. MATERIALS AND METHODS: In 41 patients, 20 TL and 22 BL
      implant procedures were carried out. Intraoral radiographs of all of the 42 sites
      were taken immediately after implant insertion as well as during the follow-up
      examination. The analysis of bone height was conducted using a computerized
      technique. The TRAN method was used to determine the gingival biotype. RESULTS:
      After a mean in situ period of 4.9 years in the TL group, 12 implants with a
      thick biotype had a mean bone loss of 0.21 mm (SD: 0.43 mm). The eight implants
      with a thin biotype had a loss of 0.05 mm (SD: 0.47 mm; P = .31). After a mean in
      situ period of 1.9 years, the 14 BL sites with a thick biotype showed a mean bone
      change of -0.03 mm (SD: 0.38 mm). In the eight implants with a thin biotype, a
      change of +0.09 mm (SD: 0.32 mm; P = .84) was noted. CONCLUSION: Analysis of the
      obtained results did not reveal a dependency of bone height on implant design or
      on gingival biotype. However, prior to choosing an implant design, it may
      nevertheless be beneficial to screen for transparent soft tissues, where the BL
      design offers a more natural emergence profile. For this purpose, the TRAN method
      is clearly the fastest and easiest.

PMID- 30231101
TI  - Pink Esthetic Score Outcomes Around Three Implant-Abutment Configurations: 3-Year
      Results.
AB  - PURPOSE: To evaluate the influence that three different implant-abutment
      interface designs had on peri-implant mucosal outcomes as assessed by the pink
      esthetic score (PES) 3 years after delayed implant placement and immediate
      provisionalization. MATERIALS AND METHODS: Adult subjects (n = 141) requiring
      replacement of a bounded single tooth in the anterior maxilla as well as first
      premolar sites were randomized to receive one of three unique implant-abutment
      interface designs (conical interface [CI]; flat-to-flat interface [FI]; or
      platform-switch interface [PS]). Treatment included immediate provisionalization
      with prefabricated titanium abutments, followed by custom computer-aided
      design/computer-aided manufacturing (CAD/CAM) zirconia abutments and cement
      retained, all-ceramic crowns delivered after 12 weeks. Bilateral (anterior sites)
      or unilateral (premolar sites) digital clinical photographs were made at 1, 3, 6,
      12, 24, and 36 months post-implant placement. Five calibrated faculty evaluators
      who previously scored the 1-year PES image dataset scored the 24- and 36-month
      photographs using a digital, cloud-based tablet interface. RESULTS: Six hundred
      ten clinical photographs were evaluated, resulting in a total of 3,050 sum PES
      values and 21,350 individual PES values. Faculty evaluator intrarater and
      interrater reliability were found to be "substantial," with intraclass
      correlation coefficient (ICC) values of 0.76 and 0.77, respectively. All three
      implant-abutment interface groups demonstrated acceptable esthetics at 3 years
      (mean sum PES = 10.1 +/- 1.9, 4.0 to 13.2), with no single group demonstrating
      significantly greater mean sum PES values than another at the 3-year follow-up or
      at any recall interval in between. CONCLUSION: No significant differences were
      observed in mean sum PES scores for subjects randomized to one of three different
      implant-abutment interface geometries. Within the limitations of this study thus
      far, the first 6 months following definitive prosthesis delivery appear to still
      be the most significant with regard to improvement in PES outcomes for all three
      treatment groups.

PMID- 30231102
TI  - Sinus Augmentation Failure and Postoperative Infections Associated with
      Prophylactic Clindamycin Therapy: An Observational Case Series.
AB  - PURPOSE: This observational study was based on a series of clinical cases in
      which failure of sinus augmentations occurred in patients who received
      prophylactic clindamycin therapy. MATERIALS AND METHODS: Between the years 2006
      and 2010, a retrospective observational study was performed. The study consisted
      of 1,874 patients (723 males and 1,151 females) in whom sinus augmentations were
      performed prior to placement of dental implants. RESULTS: In nine (0.48%)
      patients (four males and five females), infection of the graft material inside
      the sinus floor occurred, and six patients developed an abscess in the site of
      surgery, 4 to 6 weeks postoperatively. In three patients, a buccal fistula with
      pus draining was observed 5 to 8 weeks postoperatively. In all patients, the
      source of infection was from the grafted material within the sinus. A common
      manifestation in all nine patients was that they had self-reported penicillin
      allergy and had been prescribed clindamycin (300 mg every 6 hours for 10 days).
      CONCLUSION: Prophylactic clindamycin therapy following sinus augmentation
      procedures seems to be a risk factor for infections and loss of grafting material
      following these surgical techniques.

PMID- 30231103
TI  - Rehabilitation of a Severely Resorbed Posterior Mandible with 4-mm Extra-Short
      Implants and Guided Bone Regeneration: Case Report with 3-year Follow-up.
AB  - Alveolar bone resorption has been a major challenge for implant placement in
      regions limited by anatomical structures. New alternatives have been introduced
      with the inclusion of extra-short implants in dentistry. The association of
      guided bone regeneration (GBR) with the use of extra-short implants might be a
      viable alternative for regions with limited bone height. This case report aimed
      to present the rehabilitation of a patient with severe mandibular bone resorption
      in the posterior region. The association of GBR with the use of extra-short
      implants was a viable alternative after a 3-year follow-up.

PMID- 30231104
TI  - Study on Oral Health-Related Quality of Life in Patients After Dental Implant
      Treatment with Patient-Reported Outcome.
AB  - PURPOSE: The objective of this study was to use patient-reported outcome to
      explore patient characteristics that influence the oral health-related quality of
      life of post-implant patients. MATERIALS AND METHODS: The study design was a
      nested case-control study. The target population was patients who had undergone
      implant treatment at the Department of Oral Implantology, Osaka Dental
      University, with a superstructure fitted >= 3 months previously. The survey
      period was from April 2014 to the end of October 2016. Oral health-related
      quality of life was evaluated using the General Oral Health Assessment Index
      (GOHAI). The relationship between patient characteristics and oral health-related
      quality of life was investigated by binomial logistic regression analysis. The
      Japanese GOHAI norm for the 50s and 60s age groups was used as the dependent
      variable for comparison with this study population. Explanatory variables were
      age, sex, time of survey, implant site, type of superstructure, pre-implant
      number of molar occlusal support zones, pre-implant deficit status, and number of
      missing teeth. RESULTS: Of the total of 1,967 subjects, data were missing for 176
      subjects, the time of survey was < 3 months since fitting of the superstructure
      for 1,021 subjects, and 123 subjects did not meet the inclusion criteria.
      Therefore, 647 subjects were finally analyzed. As a result of implant treatment,
      64.5% of subjects exceeded the Japanese GOHAI norm for the same age group (52.2).
      From logistic regression analysis, patient characteristics that were extracted as
      influencing oral health-related quality of life were age < 65 years (odds ratio:
      1.8); women (odds ratio: 1.8); and 1 pre-implant molar occlusal support zone
      (reference value of 4 zones) (odds ratio: 2.5). CONCLUSION: This study showed
      that implant treatment is an effective method for dental prosthetic treatment
      from the perspective of patient-reported outcome. In addition, patient
      characteristics that influence the oral health-related quality of life of post
      implant patients were shown to be age < 65 years, women, and one pre-implant
      molar occlusal support zone. This study may help to predict posttreatment oral
      health-related quality of life and determine treatment plans.

PMID- 30231105
TI  - Crestal Sinus Floor Augmentation Using Hydraulic Pressure and Vibrations: A
      Retrospective Single Cohort Study.
AB  - PURPOSE: To evaluate the sinus membrane perforation and implant survival rate
      after crestal minimally invasive sinus floor augmentation using hydraulic
      pressure and vibrations. MATERIALS AND METHODS: In this retrospective single
      cohort study, all patients who underwent minimally invasive sinus floor
      augmentation between 2007 and 2015 using hydraulic pressure and vibrations were
      included. The sinus membrane is elevated by physiologic saline at 1.5 bar. The
      fluid is then set into vibration to further separate the sinus membrane from the
      bony floor. The endpoints were sinus membrane perforation and the survival rate
      of implants. RESULTS: The hydraulic pressure and vibration technique was applied
      in 156 patients. Seven patients with perforations of the sinus membrane were
      treated with the lateral window approach and excluded from the follow-up
      analysis. In the remaining 149 patients, 184 crestal sinus floor augmentations
      were performed and 184 implants were placed. In 10 of these 184 cases, a
      perforation was suspected in the postoperative computed tomography (CT) scan. In
      total, the perforation rate was 8.9% (17/191). Nineteen implants were lost during
      the follow-up period ranging from 0.2 to 8.4 years with a median of 2.3 years.
      The cumulative implant survival rates after 1, 3, and 5 years were 94.4%, 87.7%,
      and 87.7%, respectively. No severe perioperative complications were noted.
      CONCLUSION: The hydraulic pressure and vibration technique allows a minimally
      invasive crestal sinus augmentation with a perforation rate less than 10% and
      implant survival rates of approximately 90%.

PMID- 30231106
TI  - A Prospective, Randomized, Open-Label Study Comparing an Opioid-Sparing
      Postsurgical Pain Management Protocol With and Without Liposomal Bupivacaine for
      Full-Arch Implant Surgery.
AB  - PURPOSE: Mild to moderate pain is common following dental implant surgeries,
      although severe pain is reported in some patients. This randomized, open-label
      trial was designed to determine the efficacy and safety of an opioid-sparing
      postsurgical pain management protocol with or without local infiltration of
      liposomal bupivacaine for full-arch implant surgery. This procedure is used in
      edentulous and/or failing dentition patients and involves securing four or more
      implants to the maxilla and/or mandible to serve as anchors for dental
      prostheses. MATERIALS AND METHODS: Patients scheduled to undergo full-arch
      implant surgery were randomly assigned to receive an opioid-sparing postsurgical
      pain management protocol with or without liposomal bupivacaine 266 mg at the end
      of surgery. All patients received infiltration with <= 40 mL lidocaine 2% with
      epinephrine at the beginning of surgery and bupivacaine 0.5% with epinephrine
      near the end of surgery and oral opioid or nonopioid analgesics (oxycodone 5 mg
      tablets or ibuprofen 600 mg), as needed, postsurgically. Pain severity at the
      surgical site was assessed using a verbal 0 to 10 numeric rating scale (0 [no
      pain] to 10 [worst pain imaginable]). Patients separately assessed pain in their
      mandible and maxilla. Reports of treatment-emergent adverse events were
      collected. RESULTS: Sixty-nine patients were randomized to the liposomal
      bupivacaine 266 mg (n = 34) or control group (n = 35). At all time points
      postsurgery for both the mandible (all P <= .0112) and the maxilla (all P <=
      .0083), the liposomal bupivacaine group reported significantly less cumulative
      pain than the control group. At the conclusion of the 7-day follow-up, patients
      in the liposomal bupivacaine group experienced one-third less cumulative
      postsurgical pain than patients in the control group. Seventy-seven percent of
      patients in the liposomal bupivacaine group and 80% in the control group
      experienced a treatment-emergent adverse event. A higher percentage of patients
      in the liposomal bupivacaine versus control group reported itching (15% vs 9%)
      and constipation (38% vs 23%). CONCLUSION: Patients receiving an opioid-sparing
      postsurgical pain management protocol with liposomal bupivacaine 266 mg
      experienced a statistically significant reduction of postsurgical pain and
      clinically relevant reduction in opioid consumption. The overall incidence of
      treatment-emergent adverse events was comparable in patients receiving an opioid
      sparing postsurgical pain management protocol with or without liposomal
      bupivacaine.

PMID- 30231111
TI  - Characteristics of auditory evaluation in Williams syndrome: a systematic review.
AB  - PURPOSE: Identify the characteristics of the clinical audiological evaluation of
      individuals with Williams syndrome by means of a systematic literature review.
      RESEARCH STRATEGIES: The following research question was initially determined:
      "What are the characteristics of clinical auditory assessment in individuals with
      Williams syndrome?". From this, a bibliographic search was conducted in four
      databases using the descriptors: Williams syndrome, Hearing loss, and Audiology.
      SELECTION CRITERIA: Only full articles with evidence levels 1 or 2, published in
      Brazilian Portuguese or English, were selected. DATA ANALYSIS: Results obtained
      in the auditory tests used in the clinical routine, namely: immittance test, pure
      tone audiometry, otoacoustic emissions, and brainstem auditory evoked potential
      were analyzed. RESULTS: Two hundred nine studies were found, but only 12 met the
      inclusion criteria for the study. It was possible to observe prevalence of type A
      tympanometry curve, which may occur with absence of acoustic reflexes, mild to
      moderate sensorineural hearing loss, affecting mainly the high frequencies,
      absent or less amplified otoacoustic emissions, and brainstem auditory evoked
      potential without retrocochlear alteration. CONCLUSION: Cochlear impairment is
      common in individuals with Williams syndrome and the main disorders found in the
      hearing assessment in this population are absence of otoacoustic emissions and
      acoustic reflexes, as well as presence of mild to moderate sensorineural hearing
      loss, mainly in the high-frequency range, observed by audiometry.

PMID- 30231112
TI  - Multiplex polymerase chain reaction as an improved method for screening
      Histoplasma capsulatum mating types.
AB  - Histoplasmosis is a systemic mycosis infection caused by Histoplasma capsulatum,
      a heterothallic ascomycete. The sexual reproduction of this fungus is regulated
      by the mating type (MAT1) locus that contains MAT1-1 and MAT1-2 idiomorphs, which
      were identified by uniplex polymerase chain reaction (PCR). This study aimed to
      optimise single-step multiplex PCR for the accurate detection of the distinct
      mating types of H. capsulatum. Among the 26 isolates tested, 20 had MAT1-1
      genotype, while six showed MAT1-2 genotype, in agreement with the uniplex PCR
      results. These results suggest that multiplex PCR is a fast and specific tool for
      screening H. capsulatum mating types.

PMID- 30231113
TI  - Colonoscopy complications: experience with 8968 consecutive patients in a single
      institution.
AB  - OBJECTIVE: to evaluate the incidence, epidemiological characteristics, diagnosis
      and evolution of patients who returned to the emergency care units of the Albert
      Einstein Hospital in Sao Paulo/SP with signs and symptoms suggestive of
      colonoscopy complications up to 30 days after the procedure. METHODS: we
      conducted a retrospective, uni-institutional study of patients submitted to
      colonoscopy in 2014 who returned to the Emergency department (ED) within 30 days
      after the procedure. RESULTS: 8968 patients underwent colonoscopies, 95 (1.06%)
      of whom had complaints related to possible complications. Most of the procedures
      were elective ones. Minor complications (nonspecific abdominal pain/distension)
      were frequent (0.49%) and most of the patients were discharged after consultation
      at the ED. Severe complications were less frequent: perforation (0.033%), lower
      gastrointestinal bleeding (0.044%), and intestinal obstruction (0.044%). ED
      consultations in less than 24 hours after the procedure was associated with a
      higher index of normal colonoscopies (p=0.006), more diagnosis of fever
      (p=0.0003) and dyspeptic syndrome (p=0.043), and less diagnosis of
      colitis/ileitis (p=0.015). The observation of fever in patients treated at the ED
      was associated with the diagnosis of polyps at colonoscopy (p=0.030). CONCLUSION:
      the data corroborate the safety of the colonoscopy exam and points to a reduction
      in major complications rates.

PMID- 30231114
TI  - How to reduce pleural drainage complications using an ultrasound- guided
      technique.

PMID- 30231115
TI  - Life experience of adolescent drug users: a phenomenological approach.
AB  - OBJECTIVE: To understand the life experience of adolescents who use illicit
      drugs. METHOD: A phenomenological qualitative study conducted in a Youth
      Integration Center of Sinaloa Mexico from October 2016 to July 2017. The
      phenomenological interview was conducted with 11 adolescent informants and was
      based on a leading question. Heideggerian hermeneutics were used as a reference
      for the analysis of the narratives that identified the phenomenon described.
      RESULTS: Three categories expressed the phenomenon: family roughness, which
      revealed a violent, oppressive world lacking in affection and moral values;
      experimenting in the world of drug use, which revealed its existence and
      experimentation with several drugs and the novelty in that world; and the hope of
      "being there", which portrays an individual with possibilities to coexist with
      themselves, society, family, loved ones and their spirituality. CONCLUSION: The
      understanding of the life experience reflects the adolescent drug user's need for
      sensitive and comprehensive human care provided by a multidisciplinary health
      team.

PMID- 30231116
TI  - Scientific production on workplace bullying and nursing: a bibliometric study.
AB  - OBJECTIVE: To verify bibliometric indicators of the scientific production
      available in online journals that approach workplace bullying and nursing.
      METHOD: A bibliometric study making use of Bradford's law, Zipf's law, and
      textual statistics was carried out with publications in Portuguese, English, and
      Spanish, made available in national and international databases, from 2000 to
      2016. RESULTS: The sample was made up of 111 publications. The main authors had
      connections with 91 institutions distributed in 24 countries. The United States,
      Brazil, and Australia were the countries with the most publications. The
      populations of the studies were made up of nursing professionals and students,
      and the hospital environment was the most studied setting. The journals with a
      higher number of publications have international scientific influence. The terms
      that presented greater semantic power and high frequency in the abstracts were:
      bullying; assedio moral; and acoso laboral. CONCLUSION: Indicators showed that
      workplace bullying occurs in the nursing work environments of several countries,
      and the number of publications on this theme has tended to increase. Diversifying
      methods and study settings is important to contribute to the advancement of
      knowledge and fight against this violence.

PMID- 30231117
TI  - Assistive technology and active aging according to professionals working in
      community groups.
AB  - OBJECTIVE: To identify the knowledge of professionals about assistive technology
      and its importance in the elderly's life. METHOD: Exploratory descriptive
      qualitative study performed with professionals working in three community groups
      in the city of Cajazeiras (state of Paraiba/PB). Data were collected through an
      interview with semi-structured script and analyzed according to the Content
      Analysis Technique. RESULTS: Participation of 45 professionals. Four categories
      were identified, namely: Knowledge about assistive technology; Professionals'
      lack of knowledge about available assistive technologies for implementation in
      work with the elderly; Use of assistive technology by the elderly; Impact on
      professional practices after implementation of assistive technology. CONCLUSION:
      Some of professionals have knowledge about assistive technology and others make a
      wrong interpretation by confusing it with working instruments. In spite of the
      positive impact of assistive technology on certain professionals' practice, there
      is need for training in order to provide a better use of assistive technologies
      by the elderly.

PMID- 30231118
TI  - International academic mobility: the experience of undergraduate nursing
      students.
AB  - OBJECTIVE: To understand/reveal the experiences of undergraduate students of the
      Nursing School of the Universidade de Sao Paulo in international academic
      mobility. METHOD: A cross-sectional, descriptive study with a qualitative
      approach conducted between February and July 2017. Data were collected using a
      semi-structured interview and submitted to content analysis. RESULTS: Twenty-two
      (22) students participated in the study. Five analytical categories emerged from
      the analysis of the interviews: Interinstitutional Relationships Dimension,
      Personal Dimension, Professional Dimension, Academic Dimension and Cultural
      Dimension. CONCLUSION: There are many advantages that international mobility can
      bring to vocational training. Greater governmental and institutional investment
      is considered necessary, but with mutual planning and monitoring by the
      institutions in order for it to contribute to the development of Nursing and the
      Country.

PMID- 30231119
TI  - Factors associated with the knowledge of patients and caregivers about clean
      intermittent urethral catheterization: an integrative review.
AB  - OBJECTIVE: To identify the factors associated with the knowledge of patients and
      caregivers about Clean Intermittent Urethral Catheterization in the literature
      which hinder or facilitate the procedure. METHOD: An integrative review of the
      literature conducted in the MEDLINE/PubMed, CINAHL, Cochrane, Web of Science,
      SCOPUS and LILACS databases. RESULTS: 13 primary studies were included in the
      sample after the peer review. A synthesis of knowledge was performed in two
      categories: Factors associated with the knowledge of patients and caregivers
      which hinder the procedure and Factors associated with the knowledge of patients
      and caregivers which facilitate the procedure. Factors that hinder and facilitate
      the procedure respectively related to the need of information and negative
      feelings, use of easy-to-understand language, and application of information
      leaflets, among others. CONCLUSION: There is a shortage of published articles on
      the subject, and those which were identified had a low level of evidence,
      therefore requiring greater commitment and effort on the part of health
      professionals and researchers to use more robust designs.

PMID- 30231120
TI  - Managing anxiety in Parkinson's disease: the role of nonpharmacological
      strategies.

PMID- 30231121
TI  - The effect of resistance training on the anxiety symptoms and quality of life in
      elderly people with Parkinson's disease: a randomized controlled trial.
AB  - OBJECTIVES: To assess the effects of resistance training on the anxiety symptoms
      and quality of life in patients with Parkinson's disease. METHODS: Thirty-five
      elderly patients were randomly divided into two groups: 17 patients in the
      control group and 18 in the intervention group. All patients maintained standard
      pharmacological treatment for Parkinson's disease, but the intervention group
      participated in a 24-week resistance training program. The anxiety symptoms were
      assessed through the Beck's Anxiety Inventory, and quality of life by the
      Parkinson's Disease Questionnaire-39. RESULTS: There was a significant reduction
      in anxiety level and increase in quality of life after 24 weeks of resistance
      training. CONCLUSION: The results of the present study indicate that resistance
      training is an effective intervention in the reduction of anxiety symptoms and
      improves the quality of life in elderly people with Parkinson's disease.

PMID- 30231122
TI  - Spontaneous intracranial hypotension and its complications.
AB  - Spontaneous intracranial hypotension (SIH) is a syndrome that was unknown until
      the advent of magnetic resonance imaging (MRI). It is a cause of orthostatic
      headache, which remains underdiagnosed and, rarely, can result in several
      complications including dural venous sinus thrombosis, subdural hematoma and
      subarachnoid hemorrhage. Some of these complications are potentially life
      threatening and should be recognized promptly, mainly by imaging studies. We
      reviewed the MRI of nine patients with SIH and describe the complications
      observed in three of these patients. Two of them had subdural hematoma and one
      had a dural venous sinus thrombosis detected by computed tomography and MRI. We
      concluded that MRI findings are of great importance in the diagnosis of SIH and
      its complications, which often influence the clinical-surgical treatment of the
      patient.

PMID- 30231123
TI  - Cross-cultural adaptation to Brazilian Portuguese of the Dementia Knowledge
      Assessment Tool Version Two: DKAT2.
AB  - OBJECTIVES: The Dementia Knowledge Assessment Tool Version Two (DKAT2) was
      developed to measure caregivers' knowledge about the trajectory of dementia and
      assess changes in the knowledge before and after educational programs. The DKAT2
      is a 21-item tool with questions about several aspects of dementia. The possible
      answers for each question are "yes", "no" or "don't know". The maximum score is
      21. The aim of the study was to cross-culturally adapt the DKAT2 to Brazilian
      Portuguese. METHODS: The essential steps to cross-culturally adapt were conducted
      and the final version administered to 30 caregivers of older people with
      dementia, sampled by convenience. RESULTS: In the sample assessed, the mean age
      was 55.7 (+/- 12.5) years, 93.3% were female, 56.7% were sons/daughters and 23.3%
      were spouses of the older adults with dementia. The mean time caring for the
      elder was 4.7 (+/- 3.3) years and 70% of the caregivers had some level of burden.
      The mean age of the older people was 82.4 (+/- 6.7) years, 19 (63.3%) had a
      diagnosis of Alzheimer's disease, 100% were dependent for instrumental activities
      of daily living and 70% had some degree of dependence for basic activities of
      daily living. The mean score for the caregivers' knowledge level was 15.0 (+/-
      2.5) correct answers. CONCLUSIONS: The Brazilian Portuguese version was developed
      and the final version is suitable for use in Brazil.

PMID- 30231124
TI  - Motor and non-motor wearing-off and its impact in the quality of life of patients
      with Parkinson's disease.
AB  - OBJECTIVES: The wearing-off phenomenon is common in patients with Parkinson's
      disease. Motor and non-motor symptoms can fluctuate in relation to the "on/off"
      periods. To assess the impact of motor and non-motor wearing-off on activities of
      daily living and quality of life of patients with PD. METHODS: A cross-sectional
      study was carried out. All patients were evaluated using the Movement Disorders
      Society Unified Parkinson's Disease Rating Scale. Wearing-off was assessed using
      the Wearing-Off Questionnaire-19, and quality of life was assessed using the
      Parkinson's Disease Questionnaire-8. RESULTS: A total of 271 patients were
      included; 73.4% had wearing-off; 46.8% had both motor and non-motor fluctuations.
      Patients with both motor and non-motor wearing-off had a worst quality of life
      compared with those with only motor fluctuations (p = 0.047). CONCLUSIONS: Motor
      and non-motor fluctuations have an impact on activities of daily living and
      quality of life. Non-motor wearing-off may have a higher impact.

PMID- 30231125
TI  - Blepharospasm with elevated anti-acetylcholine receptor antibody titer.
AB  - OBJECTIVES: To determine whether serum levels of anti-acetylcholine receptor
      antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm
      (BSP). METHODS: Eighty-three adults with BSP, 60 outpatients with hemifacial
      spasm (HFS) and 58 controls were recruited. Personal history, demographic
      factors, response to botulinum toxin type A (BoNT-A) and other neurological
      conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme
      linked immunosorbent assay. RESULTS: The anti-AChR Abs levels were 0.237 +/-
      0.022 optical density units in the BSP group, which was significantly different
      from the HFS group (0.160 +/- 0.064) and control group (0.126 +/- 0.038). The
      anti-AChR Abs level was correlated with age and the duration of response to the
      BoNT-A injection. CONCLUSION: Patients with BSP had an elevated anti-AChR Abs
      titer, which suggests that dysimmunity plays a role in the onset of BSP. An
      increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in
      BSP.

PMID- 30231126
TI  - Quality of life in individuals with spinocerebellar ataxia type 10: a preliminary
      study.
AB  - OBJECTIVES: Spinocerebellar ataxia type 10 (SCA10) is characterized by gait
      ataxia, dysarthria, nystagmus, epilepsy, reduced cognitive ability and
      depression, which lead to functional loss and behavioral changes. These signs
      gradually evolve and may interfere with the physical, emotional, and social
      aspects of quality of life (QoL). To assess the self-perception of quality of
      life and its association with disease duration, severity of ataxia, balance and
      functional independence. METHODS: This study focused on the disease duration,
      ataxia severity (SARA), balance (Berg Balance Scale), functionality (FIM, Lawton
      IADL) and QoL (SF-36 v.2) of 15 individuals with SCA10. RESULTS: The population
      sample consisted of eight females and seven males, with a mean age of 43.8 (+/-
      8.2) years, mean age of symptom onset of 33.1 (+/- 8.9) years and mean disease
      duration of 9.8 (+/- 11.2) years. The mean Berg Balance Scale score was 47.2 (+/-
      12), mean SARA score (n = 14) 11.5 (+/- 7.3), mean Lawton IADL score 20.4 (+/-
      1.8) and mean FIM score 120.3 (+/- 5.4). Individuals with SCA10 had a greater
      impairment of QoL in the "role-physical" domain (p = 0.04). The longer the
      disease duration (p = 0.02), risk of falling (p = 0.04), severity of ataxia (p =
      0.00) and functional dependence in activities of daily living (p = 0.03) and
      instrumental activities of daily living (p = 0.00), the worse the QoL was in the
      "physical functioning" domain, with a decrease of 1.62 points for each year of
      disease duration. CONCLUSION: In this sample, the greatest impairment of QoL in
      individuals with SCA10 was observed in "physical functioning" and "physical
      role".

PMID- 30231127
TI  - Tumarkin-like phenomenon as a sign of therapeutic success in benign paroxysmal
      positional vertigo.
AB  - OBJECTIVES: To describe an unusual patient reaction to maneuvers used in the
      treatment of posterior canal benign paroxysmal positional vertigo (PC-BPPV) that
      we termed the "Tumarkin-like phenomenon". METHODS: At a private practice, 221
      outpatients were diagnosed and treated for PC-BPPV. The treatment consisted of
      performing the Epley or Semont maneuvers. At the end of these maneuvers, when
      assuming the sitting position, the patients' reactions were recorded. RESULTS:
      Thirty-three patients showed a Tumarkin-like phenomenon described by a self
      reported sensation of suddenly being thrown to the ground. In the follow-up, this
      group of patients remained without PC-BPPV symptoms up to at least 72 hours after
      the maneuvers. CONCLUSION: The occurrence of a Tumarkin-like phenomenon at the
      end of Epley and Semont maneuvers for PC-BPPV may be linked with treatment
      success.

PMID- 30231129
TI  - Twenty-five years since the identification of the first SCA gene: history,
      clinical features and perspectives for SCA1.
AB  - Spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous
      group of monogenic diseases that share ataxia and autosomal dominant inheritance
      as the core features. An important proportion of SCAs are caused by CAG
      trinucleotide repeat expansions in the coding region of different genes. In
      addition to genetic heterogeneity, clinical features transcend motor symptoms,
      including cognitive, electrophysiological and imaging aspects. Despite all the
      progress in the past 25 years, the mechanisms that determine how neuronal death
      is mediated by these unstable expansions are still unclear. The aim of this
      article is to review, from an historical point of view, the first CAG-related
      ataxia to be genetically described: SCA 1.

PMID- 30231128
TI  - Brazilian Consensus for the Treatment of Multiple Sclerosis: Brazilian Academy of
      Neurology and Brazilian Committee on Treatment and Research in Multiple
      Sclerosis.
AB  - The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more
      effective and personalized treatment, but the choice and management of disease
      modifying therapies (DMTs) is becoming increasingly complex. In this context,
      experts from the Brazilian Committee on Treatment and Research in Multiple
      Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy
      of Neurology have convened to establish this Brazilian Consensus for the
      Treatment of MS, based on their understanding that neurologists should be able to
      prescribe MS DMTs according to what is better for each patient, based on up-to
      date evidence and practice. We herein propose practical recommendations for the
      treatment of MS, with the main focus on the choice and management of DMTs, as
      well as present a review of the scientific rationale supporting therapeutic
      strategies in MS.

PMID- 30231130
TI  - Margaret Dix, Charles Hallpike and the 'Lagerungs' Manoeuvre.
AB  - The main objective of this manuscript is to describe some personal and
      professional aspects of two outstanding researchers and pioneers in neuro
      otology. Among other achievements, Margaret Ruth Dix, and Charles Skinner
      Hallpike, designed the most-used provocative test for positional nystagmus for
      the diagnosis of lithiasis in the vestibular posterior semicircular canal.

PMID- 30231131
TI  - Primary central nervous system post-transplant lymphoproliferative disorder
      mimicking toxoplasmosis.

PMID- 30231132
TI  - Added value of arterial spin-labeling (ASL) and susceptibility weighted-images
      (SWI) in detecting a mild symptomatic intracranial arteriovenous fistula.

PMID- 30231133
TI  - Perforating palmar disease in TTR-related familial amyloid polyneuropathy.

PMID- 30231134
TI  - Management of chronic subdural hematoma in Brazil.

PMID- 30231135
TI  - Reply.

PMID- 30231136
TI  - Herbivore, parasitoid and hyperparasitoid insects associated with fruits and
      seeds of Enterolobium contortisiliquum (Vell.) Morong (Fabaceae).
AB  - This study aimed to inventory the herbivore insects associated with Enterolobium
      contortisiliquum (Vell.) Morong (Fabaceae) fruits and seeds and their primary and
      secondary parasitoids. Six samples collected between May and October 2013 yielded
      210 fruits, from which 326 insects of six orders emerged: Coleoptera,
      Hymenoptera, Lepidoptera, Diptera, Thysanoptera and Psocoptera. Coleoptera (five
      families) was represented by the seed consumers Merobruchus bicoloripes Pic,
      Stator sp. Bridwell (Chrysomelidae, Bruchinae), two species of Silvanidae, one
      species of Scolytinae (Curculionidae), one species of Nitidulidae and one species
      of Cerambycidae. The cerambycid was also observed forming galleries on fruit
      mesocarp. Immature individuals of Lepidoptera were observed consuming the fruits
      and seeds. From the seven Hymenoptera families, only two species were associated
      with Coleoptera, being Horismenus Walker sp. (Eulophidae) as parasitoid of M.
      bicoloripes, and Neoheterospilus falcatus (Marsh) (Braconidae) as parasitoid of
      Scolytinae. The Lepidoptera parasitoids represented four genera:
      Pseudophanerotoma Zetel, Chelonus Panzer (Braconidae), Orgilus Nees (Braconidae)
      and Goniozus Forster (Bethylidae). The host associations for the reared
      parasitoids Bracon Fabricius (Braconidae), Pimplinae sp. (Ichneumonidae) and
      Perilampus Forster (Perilampidae) were not confirmed. We obtained a single
      representative of Diptera (Tachinidae) associated with Lepidoptera hosts in this
      food web.

PMID- 30231137
TI  - Faunistic analyses of fruit fly species (Diptera: Tephritidae) in orchards
      surrounded by Atlantic Forest fragments in the metropolitan region of Curitiba,
      Parana state, Brazil.
AB  - The objective of this trial was to characterize the assemblage structure of fruit
      flies (Diptera: Tephritidae) by determining the diversity and faunal indices.
      Fruit flies were collected for ten years between 2003 and 2015 in six
      municipalities of the Metropolitan Region of Curitiba, Parana. The orchards were
      divided into three crop protection strategies: organic, conventional, and
      integrated pest management. The characteristic of each community was determined
      using the Shannon-Wiener, Margalef, and Pielou's indexes. The frequency,
      constancy, and dominance indexes were also determined. Biological material was
      analyzed using the explanatory variables: site, crop, plant protection strategy,
      and susceptibility period. A total of 8,089 fruit flies were collected, of which
      4,681 were females. The species Anastrepha daciformis Bezzi, A. dissimilis Stone,
      A. distincta Greene and A. pickeli Lima were recorded for the first time in
      Parana State, the occurrence of three other species was recorded for the first
      time in the Metropolitan Region of Curitiba (A. montei Lima, A. obliqua Macquart,
      and A. sororcula Zucchi), in addition A. fraterculus (Wiedemann), A. grandis
      (Macquart) and Ceratitis capitata (Wiedemann). A. fraterculus accounted for 98.5%
      of the collected species. Only A. fraterculus and A. sororcula were found in
      fruits. Fruit flies occurred predominantly in peach trees cultivated under
      organic conditions. The Shannon index indicated that the municipality of Cerro
      Azul had the highest diversity and richness whereas apple orchards had the lowest
      diversity. Crops cultivated under organic conditions exhibited the highest
      diversity whereas those cultivated under conventional conditions had the highest
      evenness index. The largest specimens number was collected during the period of
      crop susceptibility.

PMID- 30231138
TI  - Volatilization of ammonia in systems of treatment of swine manure with aquatic
      macrophytes.
AB  - The usage of aquatic plants represents an alternative in the treatment of
      residues originating from swine. In these systems, one of the N removal methods
      is the ammonium (NH4 +) uptake and volatilization of ammonia (NH3). In this way,
      the objective of this work was to evaluate the volatilization rates of NH3 in
      waste treatment systems swine fluids (SSF) with aquatic macrophytes, as well as
      the concentration of NH 4+ present in the swine fluids. The experiment was
      carried out at Campus II/UNOESTE. The treatment systems were composed of 16 boxes
      of PVC and characterized as: T1 = Control sample 50% of SSF/50% of water; T2 =
      50% SSF/50% water + Eichhornia crassipes (Mart.) Solms; T3 = 50% SSF/50% water +
      Pistia stratiotes L.; T4 = 50% SSF/50% water + Salvinia auriculata Aubl. The
      design was randomized blocks, with 4 treatments and 4 replicates. The hydrogen
      potential (pH) and the NH4 + content of the effluent were analyzed weekly, and
      the volatilization of NH 3 by means of collectors installed in each treatment
      unit. The presence of aquatic macrophytes promoted the reduction of NH4+
      concentration and of the pH values of swine fluids, and this resulted in the
      reduction of NH3 volatilization rates to the environment, with emphasis on the
      system with Eichhornia crassipes (Mart.) Solms, which presented the lowest rate
      of volatilization.

PMID- 30231139
TI  - New distribution record of Epipompilus aztecus (Cresson, 1869) (Hymenoptera:
      Pompilidae) in the Brazilian Pantanal.
AB  - Epipompilus aztecus (Cresson, 1869) was registered in South America in 2010. The
      aim of this paper is to report the first record of E. aztecus in the Brazilian
      Pantanal. Two female individuals of E. aztecus were collected in the northern
      portion of the Brazilian Pantanal in Mato Grosso State during November 2015. This
      new record of E. aztecus represents a range extension for the species.

PMID- 30231140
TI  - Marsupial vena cava mimicking lymph node enlargement on tomography.

PMID- 30231141
TI  - Latent tuberculosis infection and tuberculosis in children and adolescents.
AB  - OBJECTIVE: To describe the characteristics of patients diagnosed with
      tuberculosis and latent tuberculosis infection. METHODS: A retrospective study,
      between 2012 and 2015, with data from patients of Programa Einstein na Comunidade
      de Paraisopolis. To evaluate possible factors associated with patient's sex and
      diagnoses of tuberculosis and latent tuberculosis infection, chi2 or Fisher's
      exact tests were used for qualitative variables, and Mann-Whitney test for
      quantitative or ordinal qualitative variables. RESULTS: A total of 77 patients
      were evaluated. Age ranged from 6 months to 13.4 years, with a majority of males
      (54.5%), aged zero to 4 years (54.5%), diagnosed with latent tuberculosis
      infection (64.9%), and classified as eutrophic (71.2%). The tuberculin test was
      positive in 92% and in most cases the values were above 10mm (68.0%).
      Approximately three-quarters of chest X-ray tests were normal (72.7%). After
      chest X-ray, computed tomography of thorax was the most ordered exam (29.9%),
      followed by smear and culture for Mycobacterium tuberculosis in the gastric
      aspirate (28.6%). The frequencies of altered chest X-ray (70.4% versus 4.0%),
      computed tomography of thorax requests (55.6% versus 16.0%) and other tests
      requested (81.5% versus 38.0%) were significantly higher in patients with a
      diagnosis of tuberculosis, relative to those with latent tuberculosis infection,
      respectively. CONCLUSION: In our sample, proportions of altered chest X-ray, and
      performing computed tomography of thorax and other tests in patients diagnosed
      with tuberculosis were higher than in those with latent tuberculosis infection.

PMID- 30231142
TI  - Types and frequency of errors in the preparation and administration of drugs.
AB  - OBJECTIVE: To identify compatibility, types and frequency of errors in
      preparation and administration of intravenous drugs. METHODS: A cross-sectional
      and descriptive study performed at the emergency department of a university
      hospital in the city of Sao Paulo (SP). The sample consisted of 303 observations
      of the preparation and administration of intravenous drugs by nursing aides,
      nursing technicians and registered nurses, using a systematized script, similar
      to a checklist. The following variables were collected: errors related to
      dispensing, omission, schedule, unauthorized administration, dosage, formulation,
      incompatibility, preparation and administration. RESULTS: In the preparation
      stage, the following errors were identified: no hand hygiene (70.29%), and no use
      of aseptic technique (80.85%). Upon administration, no hand hygiene (81.18%), and
      no use of aseptic technique (84.81%). In 31.35% of observations, there was more
      than one medication at the same time for the same patient, of which 17.89% were
      compatible, 56.84% were incompatible and 25.26% were not tested, according to the
      Micromedex database. CONCLUSION: In both preparation and administration stages,
      the most frequent errors were no hand hygiene and no use of aseptic technique,
      indicating the need to develop and implement education programs focused on
      patient safety.

PMID- 30231143
TI  - Analysis of the muscle tissue of Wistar rats submitted to the sciatic nerve
      compression model and cryotherapy.
AB  - OBJECTIVE: To evaluate the effects of right sciatic nerve compression and
      cryotherapy on muscle tissue. METHODS: We used 42 male Wistar rats, subdivided in
      the following Groups Control, Injury 3, Injury 8 and Injury 15 submitted to nerve
      compression and euthanized in the 3rd, 8th and 15th day after surgery. The
      Cryotherapy Injury 3 was entailed treatment with cryotherapy by immersion of the
      animal in recipient for 20 minutes during 1 day, then animals were euthanized at
      the 3rd day after surgery, and the Cryotherapy Injury 8 and the Cryotherapy
      Injury 15 was treated for 6 days, and euthanized at the 8th and 15th day after
      surgery. Functional evaluation was performed by the grasping strength of the
      right pelvic limb. The right tibialis anterior muscles were evaluated for mass,
      smaller diameter and cross-sectional area. In the Cryotherapy Injury 8 and the
      Cryotherapy Injury 15 groups, the hydroxyproline was dosed in the right soles.
      RESULTS: In the compression there was a significant difference in the Injury
      Groups compared with the Control Group (p<0.05). In the smaller diameter, the
      compression in Control Group was higher than Injury 8 (p=0.0094), Injury 15
      (p=0.002) and Cryotherapy Injury 15 (p<0.001) groups. The comparison between
      groups with euthanasia in the same post-operative period, a significant
      difference (p=0.0363) was seen in day 8th after surgery, and this result in
      Cryotherapy Injury Group was greater than Injury Group. In the fiber area,
      Control Group was also higher than the Injury 8 (p=0.0018), the Injury 15
      (p<0.001) and the Cryotherapy Injury 15 (p<0.001). In hydroxyproline, no
      significant difference was seen between groups. CONCLUSION: Nerve damage resulted
      in decreased muscle strength and trophism, the cryotherapy delayed hypotrophy,
      but this effect did not persist after cessation of treatment.

PMID- 30231145
TI  - Analysis of optimal solutions in article on linear programming.

PMID- 30230903
TI  - Measurement of the Soft-Drop Jet Mass in pp Collisions at sqrt[s]=13  TeV with
      the ATLAS Detector.
AB  - Jet substructure observables have significantly extended the search program for
      physics beyond the standard model at the Large Hadron Collider. The state-of-the
      art tools have been motivated by theoretical calculations, but there has never
      been a direct comparison between data and calculations of jet substructure
      observables that are accurate beyond leading-logarithm approximation. Such
      observables are significant not only for probing the collinear regime of QCD that
      is largely unexplored at a hadron collider, but also for improving the
      understanding of jet substructure properties that are used in many studies at the
      Large Hadron Collider. This Letter documents a measurement of the first jet
      substructure quantity at a hadron collider to be calculated at next-to-next-to
      leading-logarithm accuracy. The normalized, differential cross section is
      measured as a function of log_{10}rho^{2}, where rho is the ratio of the soft
      drop mass to the ungroomed jet transverse momentum. This quantity is measured in
      dijet events from 32.9  fb^{-1} of sqrt[s]=13  TeV proton-proton collisions
      recorded by the ATLAS detector. The data are unfolded to correct for detector
      effects and compared to precise QCD calculations and leading-logarithm particle
      level Monte Carlo simulations.

PMID- 30231146
TI  - Big Data use in medical research.

PMID- 30231147
TI  - Partnership for productive development of biosimilar products: perspectives of
      access to biological products in the Brazilian market.
AB  - The manufacturing process for biological products is complex, expensive and
      critical to the final product, with an impact on their efficacy and safety. They
      have been increasingly used to treat several diseases, and account for
      approximately 50% of the yearly budget for the Brazilian public health system. As
      the patents of biological products expire, several biosimilars are developed.
      However, there are concerns regarding their efficacy and safety; therefore, the
      regulatory agencies establish rules to approve and monitor these products. In
      Brazil, partnership programs between national government-owned companies and
      private technology holders have been implemented, aiming at knowledge sharing,
      capacity-building and technological transfer. Such partnerships locally promote
      manufacturing of these strategic drugs at reduced costs to the public health
      system. These agreements offer mutual advantages to both the government and
      patent holders: for the former, a biotechnological development flow is
      established and enables potential cost reduction and self-sufficient production;
      whereas for the latter, exclusive sales of the product are ensured during
      technological transfer, for a fixed period.

PMID- 30231144
TI  - Sexual behaviors: study in the youth.
AB  - OBJECTIVE: To characterize sexual behaviors in a sample of adolescents and youth.
      METHODS: An analytical descriptive study using a questionnaire about sexual
      behaviors, adapted from the World Health Organization. It was distributed to
      students from a Portuguese city aged 14-24 years, during two months. Two age
      groups were defined: G1 - students aged 14-19 years; G2 - aged 20-24 years.
      RESULTS: The sample included 2,369 students, 61% females and 70% in G1. The mean
      age of first sexual intercourse was 16.4+/-1.8 years; 93% used some contraceptive
      method in the first sexual intercourse. Out of those who did not use
      contraception in the first sexual intercourse, 83% were in G1 (p<0.001).
      Emergency contraception was used at least once by 54% (63% in G2, p<0.001). Among
      those who had unprotected sexual intercourses, 9% were under the influence of
      alcohol, 53.6% were female and 53.4% were in G2 (p<0.001). Homosexual contacts
      occurred in 21% of cases; in that, 62% in G1 and 84% among females (p<0.001).
      CONCLUSION: The use of contraceptionin the first sexual intercourse was common in
      our sample. However, the number of adolescents not using any contraceptive method
      in subsequent sexual intercourses, and the high percentage of them who consider
      it unnecessary, are a concern. Unprotected sexual intercourses, as well as
      unplanned intercourses and under influence of alcohol or drugs, especially in the
      youngest, urge the need for intervention regarding sexual education.

PMID- 30231149
TI  - Burnout or the emotional impact of working with special populations.

PMID- 30231155
TI  - On the rational use of opiates in penitentiary centres. The balance between
      opiophobia and opiophilia.

PMID- 30231150
TI  - Burnout syndrome and work satisfaction in professionals of social work in prisons
      of Spain.
AB  - Introduction: The specialized literature has revealed the high prevalence of
      burnout syndrome in the workforce of different prisons worldwide, as well as the
      influence of various risk factors associated with sociodemographic and
      occupational factors linked of the emergence of this occupational health problem.
      The current study measures the level of burnout and job satisfaction among the
      group of social workers Spanish prisons. Methods: A cross-sectional analytical
      study was carried out on 59 social work professionals at the national level
      during 2017. Using ad hoc questionnaires, the participants offered information
      regarding sociodemographic, labour, Maslach Burnout Inventory and job
      satisfaction from Warr, Cook and Wall information. Results: The values obtained
      were 20.1 (standard deviation [SD]: 11.9) in the emotional exhaustion dimension,
      10.6 (SD: 5.0) in depersonalization and 27.7 (SD: 23.2), for personal
      accomplishment, and a general level of satisfaction of 55.3 (SD: 11.9). We found
      statistically significant associations and predictive values between the
      different dimensions of burnout and job satisfaction at sociodemographic (age)
      and work level (time in the profession) level. Conclusions: In line with the
      scientific literature, social workers in prison have a high level of burnout,
      especially emotional exhaustion, in addition to a moderate level of job
      satisfaction. The information offered could be useful in the elaboration of
      prevention strategies aimed at improving the occupational health of this group.

PMID- 30231156
TI  - Evaluation of choroidal perfusion changes in obese patients: ocular effects of
      insulin resistance.
AB  - PURPOSE: We aimed to evaluate choroidal per-fusion changes in obese patients
      using optical coherence tomography and dynamic contour tonometry, to determine
      whether these changes are associated with body mass index, and to assess the
      ocular effects of insulin resistance. METHODS: We retrospectively evaluated the
      data of 32 obese patients with body mass index >30 kg/m2 and 45 healthy control
      individuals. Intraocular pressure and ocular pulse amplitude values of the
      patients were measured using dynamic contour tonometry, and the mean choroidal
      thickness was measured using enhanced depth imaging optical coherence tomography.
      Insulin resistance was assessed using the homeostasis model assessment-estimated
      insulin resistance index. RESULTS: The mean choroidal thickness (294.30 +/- 60.87
      MUm) and ocular pulse amplitude (2.10 +/- 0.74) were lower, whereas the mean
      intraocular pressure (16.61 +/- 2.35 mmHg) was higher in obese patients than in
      controls. There was a significant negative correlation between body mass index
      and ocular pulse amplitude (r=-0.274; p=0.029) and an insignificant negative
      correlation between mean choroidal thickness, intraocular pressure, and body mass
      index. There was an insignificant negative correlation between homeostasis model
      assessment-estimated insulin resistance index, mean choroidal thickness, and
      intraocular pressure and significant ne-gative correlation between homeostasis
      model assessment-estimated insulin resistance index and ocular pulse amplitude
      (r=-0.317; p=0.022). CONCLUSION: We found reduced mean choroidal thickness and
      ocular pulse amplitude and increased mean intraocular pressure in obese patients.
      These changes indicated a decrease in choroidal perfusion and ocular blood flow.
      It may be possible to detect ocular blood flow changes in obese patients through
      noninvasive assessment using the choroid. The negative correlation between
      insulin resistance and ocular pulse amplitude may be associated with
      intracellular fat accumulation in obese patients.

PMID- 30231151
TI  - Syphilis, human immunodeficiency virus, herpes genital and hepatitis B in a
      women's prison in Cochabamba, Bolivia: prevalence and risk factors.
AB  - Objective: To determine the prevalence and factors associated with syphilis,
      human immunodeficiency virus (HIV), hepatitis B (HBV) and herpes type 2 (HSV2)
      among women in the prison of San Sebastian in Cochabamba (Bolivia). Material and
      methods: We carried out a cross-sectional study including a standardized
      questionnaire to assess socio-demographics characteristics and risk factors
      (sexual practices and exposure to blood); and serological tests for syphilis,
      HSV2, VIH, and HBV. We performed bivariate and multivariate analyses to test the
      associations between variables of interest and infections. Results: A total of
      219 out of 220 prisoners (99.5%) participated in the study. For syphilis, 12.8%
      of participants had both reactive tests (RPR+/TPPA+). The prevalence of HSV2 and
      VIH was 62.6% and 1.4%, respectively. Anti-HBc, indicating a resolved or chronic
      HBV, was positive in 11.9% of participants and 0.5% had active HBV (HBsAg
      positive). A low level of education was associated with syphilis, HSV2 and HBV.
      Having occasional sexual partners was associated with syphilis and HSV2. Being
      over 36 years old and having more than 3 children were associated with HBV. The
      number of sexual partners, history of prostitution and rape, having sexual
      intercourses in prison and detention time were not associated with any of these
      infections. Discussion: The prevalence of syphilis, HIV, HSV2 and HBV was higher
      in this vulnerable female population than in the general population in Bolivia.
      Control measures in detention are needed to limit the spread of these infections
      both in prisons and in the community.

PMID- 30231154
TI  - Prickling or Formication after the use of cocaine.

PMID- 30231153
TI  - Catalan contribution in the European project MEntally Disturbed Inmates Care and
      Support (MEDICS).
AB  - Objective: To know the criteria of penitentiary professionals about the causes,
      management methods and improvement proposal, in the attention and care of inmates
      suffering non-serious mental disorders. Material and methods: Activity developed
      from March to May 2015. In Catalonia, three prisons participated. Seven different
      models of anonymous and written questionnaires were distributed, designed by
      Italy, and aimed at directors, treatment teams, correctional officers, teachers,
      doctors, nursing staff and volunteers. They presented the degree of
      participation, descriptive characteristics of groups and main answers given. To
      study the association between qualitative variables, the Chi squared and the
      exact Fisher test was used. Results: Questionnaires distributed among the 744
      employees and there were obtained 174 filled (23.4%). There was more
      participation among health staff and treatment teams (88% and 36%). About the age
      of participants, doctors were the most senior group with meaningful differences
      (p <0.001). 40.7% were men and 57.7% women. Among the non-health staff 70% of
      correctional officers held a degree. Most of the total (62.4%) had their work as
      their main sources of knowledge about mental health. The main answers given are
      presented. Discussion: Almost 25% of penitentiary professionals participated in
      the MEDICS project. Most of them (67%) held a degree. There is a professional
      concern about mental disorders but not discrimination. Some groups (doctors and,
      specially, non-health professionals) believe as basic a continuing training and
      working in multidisciplinary teams.

PMID- 30231152
TI  - Prevalence of reactivity to the tuberculin test and associated factors in the
      population attended at a drug addiction center in the period 2013-2016.
AB  - Objective: Epidemiological study of prevalence, carried out at Center for Drug
      Addiction of the center of addictions of Nou Barris (Barcelona, Spain) during
      2013-2016 in order to know the prevalence of tuberculin test reactivity (TTR) and
      its predictive factors in drug-dependent population. Material and methods:
      Epidemiological and clinical variables, associated with the consumption of drugs
      and the practice of the tuberculin test, were collected. The reading rate and the
      prevalence of TTR for annual periods, as well as the predictive factors through a
      bivariate and multivariate logistic regression analysis. Results: 389 patients
      were studied (109 in 2013, 84 in 2014, 111 in 2015 and 85 in 2016) and they went
      to the reading of the TT 337 (86.6%). The prevalence of TTR was 33.2% in the
      readings. At the bivariate level, TTR was associated with sex, origin and prior
      history. In the multivariate analysis, the predictive value of age was confirmed
      (more reactivity in >=40 years; p <0.001, odds ratio [OR]: 4.85, confidence
      interval [IC]: 2.68-8.78), being male (p = 0.003, OR: 2.81, IC: 1.43-5.53), and
      being an immigrant (p <0.001; OR: 7.32, IC: 3.56-15.03). Discussion: It is
      concluded that the prevalence of TTR is high, especially in men, in those of more
      age, and in immigrants and that the drug addiction devices continue to be basic
      in the detection and monitoring of the latent tuberculosis infection.

PMID- 30231148
TI  - Isoenzymatic genotyping of Staphylococcus aureus from dairy cattle and human
      clinical environments reveal evolutionary divergences.
AB  - Background The genetic variability of 610 S. aureus isolates from the hands of
      professional dentists (A), dental clinic environment air (B), bovine milk from
      cows with and without mastitis (C), an insufflator for milking equipment (D) and
      milking environment air (E) was studied by isoenzyme genotyping and genetic and
      cluster analysis. Results Monoclonal and polyclonal patterns of S. aureus were
      detected in every bacterial population; however, isolates belonging to the same
      strain were not found among the populations, suggesting the genetic heterogeneity
      and the intrapopulation spread of strains. Genetic relationship analysis revealed
      the co-existence of highly related strains at low frequency among populations.
      Conclusion The data suggest that some strains can adapt and colonize new
      epidemiologically unrelated habitats. Consequently, the occurrence of an
      epidemiological genotypic identity can assume a dynamic character (spread to new
      habitats), however infrequently. A tendency of microevolutionary and genetic
      divergences among populations of S. aureus from human sources (AB) and bovine
      milk (DE), and especially the mammary quarter (C), is also suggested. This
      research can contribute to the knowledge on the distribution and dissemination of
      strains and the implementation of control measures and eradication of S. aureus
      in important dental clinic environments, as well as animal environments and dairy
      production.

PMID- 30231157
TI  - Visual performance of scleral lenses and their impact on quality of life in
      patients with irregular corneas.
AB  - PURPOSE: We aimed to evaluate the visual quality performance of scleral contact
      lenses in patients with keratoconus, pellucid marginal degeneration, and post
      keratoplasty astigmatism, and their impact on quality of life. METHODS: We
      included 40 patients (58 eyes) with keratoconus, pellucid marginal degeneration,
      and post-keratoplasty astigmatism who were examined between October 2014 and June
      2017 and fitted with scleral contact lenses in this study. Before fitting scleral
      contact lenses, we noted refraction, uncorrected distance visual acuity,
      spectacle-corrected distance visual acuity, uncorrected contrast sensitivity, and
      spectacle-corrected contrast sensitivity. We performed corneal topography on and
      applied a questionnaire that included the National Eye Institute Visual
      Functioning Questionnaire to all participants. We recorded corrected contrast
      sensitivity and corrected distance visual acuity on the third month after fitting
      scleral contact lenses and requested that subjects repeat the National Eye
      Institute Visual Functioning Questionnaire. RESULTS: The mean age of patients was
      28.12 +/- 13.19 years. Mean logMAR uncorrected distance visual acuity, spectacle
      corrected distance visual acuity, and corrected distance visual acuity with
      scleral contact lenses were 0.91 +/- 0.21 (0.40-1.80), 0.57 +/- 0.12 (0.10-1.80),
      and 0.16 +/- 0.02 (0.00-1.30), respectively. We observed significantly higher
      corrected distance visual acuity with scleral contact lenses compared with
      uncorrected distance visual acuity and spectacle-corrected distance visual acuity
      (p<0.05). Mean uncorrected contrast sensitivity, spectacle-corrected contrast
      sensitivity and CCS with scleral contact lenses were 0.97 +/- 0.12 (0.30-1.65),
      1.16 +/- 0.51 (0.30-1.80), and 1.51 +/- 0.25 (0.90-1.80), respectively.
      Significantly higher contrast sensitivity levels were recorded with scleral
      contact lenses compared with those recorded with uncorrected contrast sensitivity
      and spectacle-corrected contrast sensitivity (p<0.05). We found the National Eye
      Institute Visual Functioning Questionnaire overall score for patients with
      scleral contact lens treatment to be significantly higher compared with that for
      patients with uncorrected sight (p<0.05). CONCLUSION: Scleral contact lenses are
      an effective alternative visual correction method for keratoconus, pellucid
      marginal degeneration, and post-keratoplasty astigmatism. A significant increase
      in visual acuity and contrast sensitivity can be obtained with scleral contact
      lenses in patients with irregular corneas.

PMID- 30231158
TI  - Ocular delivery of moxifloxacin-loaded liposomes.
AB  - PURPOSE: To determine the release profile of moxifloxacin encapsulated in
      liposomes in the aqueous humor as a controlled release system for intracameral
      application. METHODS: Liposomes containing moxifloxacin were obtained using the
      lipid film hydration method and were characterized by particle size and
      encapsulation efficiency. Female rabbits were used for the in vivo profile
      release study. Liposomes containing moxifloxacin was injected into the anterior
      chamber of the right eye of each animal. The rabbits were divided into five
      groups, and a sample of aqueous humor was collected 2, 4, 8, 24, and 48 h after
      administration of liposomes containing moxifloxacin administration. Moxifloxacin
      concentrations in the aqueous humor were analyzed using high-performance liquid
      chromatography. RESULTS: The average size of the liposomes containing
      moxifloxacin was 60.5 +/- 0.72 nm with a particle size distribution of 0.307. The
      encapsulation efficiency of moxifloxacin in liposomes was 92.24 +/- 0.24%. The
      results of an in vivo release study of liposomes containing moxifloxacin, showed
      that the maximum moxifloxacin concentration was achieved within the first 2 h
      after administration (5.27 +/- 1.09 mg/mL) and was followed by a decrease in
      intracameral concentration (0.35 +/- 0.05 mg/mL) until the 24 h mark.
      CONCLUSIONS: The in vivo experiments resulted in liposomes containing
      moxifloxacin that were homogenous in size and exhibited high drug encapsulation
      efficiency. The results indicate that liposomes containing moxifloxacin offers a
      satisfactory aqueous humor release profile after intracameral application.

PMID- 30231159
TI  - Impact of environmental pollution on the ocular surface of Sjogren's syndrome
      patients.
AB  - PURPOSE: To evaluate the effect of air pollution on the ocular surface of
      patients with Sjogren's syndrome. METHODS: We investigated the ocular surfaces of
      thirty patients with Sjogren's syndrome and thirty healthy volunteers (control
      group) living in the Metropolitan Area of Buenos Aires. We used nitrogen dioxide
      as an indicator of exposure to air pollution. An ocular symptoms questionnaire
      was answered by all subjects, who also underwent a complete ocular surface
      ophthalmic examination-including an Ocular Surface Disease Index questionnaire,
      biomicroscopy, tear breakup time, Schirmer 1 test, corneal and conjunctival vital
      staining with fluorescein and lissamine green, tear lysozyme concentration, and
      impression cytology. RESULTS: In almost all ocular surface test findings, we
      found a positive and significant correlation between higher levels of exposure to
      air pollution and higher levels of ocular surface damage in both the control
      group and Sjogren's syndrome patients. In Sjogren's syndrome patients, the Ocular
      Surface Disease Index questionnaire, tear breakup time, vital staining and
      impression cytology showed a significant correlation between high levels of air
      pollution and ocular surface disease. In the control group, the Ocular Surface
      Disease Index questionnaire, tear breakup time, and impression cytology showed a
      significant correlation between high levels of air pollution and ocular surface
      disease. CONCLUSIONS: Here we demonstrated that in patients with dry eye syndrome
      associated with Sjogren, abnormalities of the ocular surface and eye irritation
      related to air pollution are more severe than those in the control group. We
      believe that measuring air quality should be not only an integral part of the
      evaluation of ocular surface disease but also a therapeutic consideration.

PMID- 30231162
TI  - Knowledge on the HPV vaccine among university students.
AB  - The objective is to evaluate knowledge on HPV vaccine and its use among
      university students. This is a cross-sectional study with 301 participants, of
      which 202 medical students from UERJ and UNIFESO (101 freshmen = M1 and 101 from
      the 6th year = M2) and 99 UERJ literature students (50 freshmen = L1 and 49 of
      the last year = L2). Information was obtained by questionnaires. Input and
      statistical analysis were carried out with the EPI-INFO 3.5.2 Program. Results
      showed that, among medical students, 21% of M1 and 16% of M2 used the HPV vaccine
      (p=0.35), mostly adopted by women (M1=29.7% and M2=21.3%) than men (M1=5.4% and
      M2=7.5%). Similarly, female students showed more interest in using the vaccine
      (M1=85.1% and M2=80%) than male (M1=56.2% and M2=20.5%). Among literature
      students, only women received the vaccine (L1=6.5% and L2=22.2%) and no men were
      vaccinated (p=0.04). More women expressed interest in receiving the vaccine than
      men (? L1=76%, L2=65% and ?, L1=47%, L2=40%). Comparison among genders regardless
      of the course showed that the vaccination rate is higher among women (p<0.001),
      as is the interest in being vaccinated (p=0.004). We concluded that the majority
      of male university students know less about the HPV vaccine than the female ones,
      use less and are less interested in being vaccinated, in all the groups
      interviewed. Vaccination coverage is low among the university population and is
      higher among medical students.

PMID- 30231160
TI  - Evaluation of renin and angiotensin II levels in pseudoexfoliation syndrome.
AB  - PURPOSE: Pseudoexfoliation syndrome has been linked to impaired function of the
      heart and blood vessels. We conducted a study to investigate the role of the
      renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome.
      METHODS: The subjects were 14 patients with pseudoexfoliation syndrome and 14
      healthy controls who underwent cataract extraction. Preoperative 5-ml samples of
      peripheral venous blood and perioperative aqueous humor were collected from the
      patients in both groups. Plasma and aqueous humor renin levels were analyzed by
      an immunoradiometric method, and angiotensin II levels were analyzed by
      radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value
      <0.05 was considered to indicate a statistically significant difference. RESULTS:
      The mean ages of the patients in pseudoexfoliation and control groups were 71.7
      +/- 7.1 and 67.4 +/- 9.3 years, respectively (p=0.140). The median aqueous humor
      renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75
      18.54) in pseudoexfoliation group (p=0.022). There were no differences between
      the two groups in the plasma renin, plasma angiotensin II, or aqueous humor
      angiotensin II levels. The correlations between plasma and aqueous humor renin
      levels and between plasma and aqueous humor angiotensin II levels were examined
      separately for each group; no significant correlations were observed in
      pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control
      group (r=-0.232, p=0.425; r=0.482, p=0.081). CONCLUSION: Aqueous humor renin
      levels are higher in pseudoexfoliation syndrome. The results indicate a probable
      role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies
      with larger numbers of cases are needed to clarify the precise association of
      renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.

PMID- 30231163
TI  - Thrombotic thrombocytopenic purpura associated with dengue and chikungunya virus
      coinfection: case report during an epidemic period.
AB  - The present report shows the occurrence of thrombotic thrombocytopenic purpura
      (TTP) associated with acute dengue and chikungunya virus coinfection, manifesting
      as a severe disease with high mortality potential. The patient was a 28 year-old
      man with clinical and epidemiological diagnosis of arboviruses infections who
      developed thrombocytopenia and anemia, after which oral corticosteroid therapy
      was started. On the third day of hospitalization, he showed neurological
      alterations that simulated a cerebral vascular accident, but the imaging
      examination did not identify ischemic or hemorrhagic alterations. At that moment,
      the TTP hypothesis was raised so that plasmapheresis and corticosteroid pulse
      therapy were started, have been essential for the favorable evolution of the
      case.

PMID- 30231161
TI  - Potential role of zinc in the visceromegaly regression and recovery of
      hematological parameters during treatment of visceral leishmaniasis in children
      from an endemic area.
AB  - Leishmaniasis is a disease complex with various clinical symptoms caused by
      different species of parasites of the genus Leishmania. The visceral form of the
      disease, characterized by severe symptoms is fatal, if not treated. The high
      toxicity of current antileishmanial drugs and the need for long-term treatment
      make the therapy complicated, especially in a large number of infected children.
      Hence, the search for new therapies must be intensified. Oral administration of
      the trace element zinc has been considered in alternative treatments against
      different clinical forms of leishmaniasis. This study revealed that the
      administration of zinc in children with visceral leishmaniasis, during treatment
      with amphotericin B or glucantime, accelerates the regression of the spleen
      enlargement without interfering with the recovery of hematological parameters.

PMID- 30231164
TI  - Molecular detection of Borrelia burgdorferi in free-living golden headed lion
      tamarins (Leontopithecus chrysomelas) in Rio de Janeiro, Brazil.

PMID- 30231165
TI  - First records of molluscs naturally infected with Angiostrongylus cantonensis
      (Nematoda: Metastrongyloidea) in Northeastern Brazil, including new global
      records of natural intermediate hosts.
AB  - Human neural angiostrongyliasis is an emerging infectious disease caused by
      nematode Angiostrongylus cantonensis. The present study investigated the presence
      of Angiostrongylus spp. in terrestrial molluscs collected from the following
      areas in the Metropolitan Region of Aracaju, Sergipe State, Brazil: Barra dos
      Coqueiros, Nossa Senhora do Socorro, Sao Cristovao and Aracaju. In total, 703
      specimens representing 13 mollusc species were screened for Angiostrongylus spp.
      Larvae of Angiostrongylus spp. were found in three species. Larvae recovered from
      Achatina fulica were used for experimental infection in Wistar rats (Rattus
      norvegicus). For specific identification of nematodes, the mitochondrial
      cytochrome c oxidase subunit I (COI) was sequenced from both larvae and adults
      recovered from molluscs and rats, respectively. Infection with A. cantonensis was
      detected in all municipalities and in the following three host species: Bulimulus
      tenuissimus, Cyclodontina fasciata (Barra dos Coqueiros), and A. fulica (Aracaju,
      Nossa Senhora do Socorro and Sao Cristovao). Co-infections were also found with
      Caenorhabditis sp. and Strongyluris sp. larvae. This is the first study of the
      helminth fauna associated with the terrestrial malacofauna in Sergipe State, and
      confirms that these three snail species are involved in the transmission of A.
      cantonensis in the state. In addition, B. tenuissimus and C. fasciata are newly
      reported natural hosts of the parasite.

PMID- 30231166
TI  - Tinea nigra palmaris: a clinical case in a rural Ethiopian hospital.
AB  - Tinea nigra is an infrequent, superficial fungal infection, mainly caused by
      Hortaea werneckii, which is still underreported in Ethiopia. An asymptomatic 62
      year-old male patient sought a rural hospital of Ethiopia, showing dark plaques
      on the palms of both hands. A superficial mycosis was suspected and a direct
      light microscopic mycological examination from skin scrapings revealed short
      brownish hyphae. To our knowledge, this is the first case of tinea nigra from the
      Ethiopian highlands. This may be due to the actual rarity of the condition or to
      underreporting.

PMID- 30231167
TI  - Artificial blood feeding for Culicidae colony maintenance in laboratories: does
      the blood source condition matter?
AB  - Culicidae colonization in laboratory is paramount to conduct studies aiming at a
      better understanding of mosquitoes' capacity to transmit pathogens that cause
      deadly diseases. Colonization requires female blood feeding, a necessary step for
      maturation of female's oocytes. Direct blood feeding on anesthetized mammals
      implies in a number of disadvantages when compared to artificial blood feeding.
      Consequently, laboratories worldwide have been trying to -feed female mosquitoes
      artificially in order to replace direct feeding. In this study, we compared the
      effects of direct blood feeding and artificial blood feeding on important life
      traits of three Culicidae species. Artificial feeding was performed using
      citrated or defibrinated sheep blood and citrated or defibrinated rabbit blood.
      Direct feeding was performed using anesthetized guinea pigs as the blood source
      and the experiment control. Results indicated that artificial feeding using sheep
      blood was not good enough to justify its use in the maintenance of laboratory
      colonies of Culicidae. However, artificial feeding using rabbit blood maintained
      a recovery rate always very close to the control, especially when blood was
      citrated. We concluded that artificial feeding using citrated rabbit blood can
      substitute direct feeding on mammals reducing the use of animals, eliminating the
      need to maintain a bioterium in the laboratory and reducing costs in scientific
      researches involving Culicidae vectors.

PMID- 30231168
TI  - A globally applicable PCR-based detection and discrimination of BK and JC
      polyomaviruses.
AB  - BKV and JCV belong to the Polyomaviridae family and are opportunistic agents
      associated with complications in immunocompromised individuals. Although a single
      screening assay for both viruses would be convenient, the diversity of BKV and
      JCV serotypes and genotypes is a methodological challenge. In this paper, we
      developed a PCR method able to detect and segregate BKV and JCV, despite these
      genetic discrepancies. A duplex semi-nested PCR (duplex snPCR) was designed to
      target a conserved region (639nt-1516nt) within the VP2 gene. In the first PCR, a
      primer set common to all BKV and JCV serotypes/ genotypes was used, followed by a
      semi-nested PCR with internal primers for BKV and JCV segregation. The limit of
      detection of the duplex snPCR was as low as 10 copies of BKV or JCV plasmids/MUL.
      Specific products were observed when JCV and BKV plasmids were mixed in the same
      reaction. In field sample testing, the duplex snPCR detected and distinguished
      both viruses in different biological samples. Results were confirmed by Sanger's
      sequencing. The geographical complexity of BKV and JCV serotypes and genotypes
      imposes limits to a simple and universal method that could detect each virus.
      However, we describe here a sensitive and reliable PCR technique for BKV and JCV
      diagnosis that overcomes these limitations and could be universally applied.

PMID- 30231169
TI  - Evaluation of a new brand of immunochromatographic test for visceral
      leishmaniasis in Brazil made available from 2018.
AB  - Immunochromatographic tests based on the recombinant antigen K39 represent a
      major advance in diagnosing visceral leishmaniasis (VL) in recent years. Some
      performance variations are expected and have occurred in the use of several
      commercial rapid tests, especially in different geographical settings. This is
      the first evaluation in the Americas of the test recently provided by the public
      health system in Brazil for the diagnostic of VL, the OnSiteTM Leishmania IgG/IgM
      Combo. In this first clinical test evaluation, 113 VL-positive patient samples
      and 73 negative controls were tested and a sensitivity of 91.2% and specificity
      of 94.5% were observed. These results indicate the need for further analysis and
      comparisons with the performance of other available commercial tests in order to
      define the impact of this new test on the quality of VL diagnosis in Brazil.

PMID- 30231170
TI  - Impact of malocclusion on oral health-related quality of life among
      schoolchildren.
AB  - The aim of the present study was to evaluate the prevalence and impact of
      malocclusion on oral health-related quality of life (OHRQoL) among schoolchildren
      aged 8 to 10 years and their parents in Diamantina, a town in the southeast of
      Brazil. A cross-sectional study was conducted with a sample of 390 randomly
      selected children who were subjected to a clinical oral examination. The Dental
      Aesthetic Index was used to diagnose malocclusion and the need for orthodontic
      treatment. The Child Perceptions Questionnaire (CPQ (8-10)) was used to evaluate
      the impact of malocclusion on OHRQoL. The children's parents answered the
      Brazilian Economic Criterion Questionnaire for the socioeconomic classification.
      Data analysis involved the nonparametric Kruskal-Wallis test and Spearman's
      correlation coefficients. The variables were grouped into a hierarchy of
      categories ranging from distal to proximal determinants. Poisson regression
      analysis with robust variance was performed at each level to correlate the total
      CPQ (8-10) score with the independent variables. The prevalence of malocclusion
      was 78.7%. Crossbite remained significantly associated with a negative impact on
      OHRQoL (PR = 1.28; 95%CI:1.17-1.39; p < 0.001). The prevalence of malocclusion
      was high in the sample investigated and exerted a negative impact on OHRQoL.

PMID- 30231172
TI  - A single-center 18-year experience with oral candidiasis in Brazil: a
      retrospective study of 1,534 cases.
AB  - Despite the large number of published studies about oral candidiasis and
      associated risk factors, reports of large single-center retrospective studies on
      the prevalence of oral candidiasis, risk factors, and the oral candidiasis types
      diagnosed more frequently in oral diagnostic reference centers are scarce. The
      objective of the present study was to retrospectively survey the demographic and
      clinical profiles of 1,534 patients diagnosed with candidiasis and treated at the
      Center for Diagnosis of Oral Diseases (CDOD), Pelotas Dental School, Federal
      University of Pelotas between 1997 and 2014. Using a retrospective, cross
      sectional, epidemiological design, data on race, gender, age, systemic diseases,
      oral candidiasis type and location, symptoms, and harmful habits such as smoking
      and alcohol consumption were collected. The statistical analysis was performed
      using STATA version 13.1. Risk factors for chronic atrophic candidiasis (CAC)
      were evaluated using Poisson regression with robust variance (p <= 0.05). The
      majority of patients with oral candidiasis seen at the CDOD over the 18-year
      period of analysis were Caucasian women, aged 51-60 years, nonsmokers, and
      nondrinkers, with no systemic disease, and who wore some form of dental
      prostheses. CAC was the single most common clinical type of candidiasis detected,
      and the most frequently affected oral site was the palate. These data from a
      large single-center in Brazil agree with previous evidence about the clinical and
      demographic profiles of patients with oral candidiasis.

PMID- 30231171
TI  - Caries in children with lactose intolerance and cow's milk protein allergy.
AB  - Dental caries in 5-to-8-year-old children with cow's milk protein allergy (CMPA)
      and lactose intolerance (LI), their treatment needs, and the consumption of milk
      based products and milk derivatives by these patients were investigated. A cross
      sectional study was undertaken with 200 children in southern Brazil in 2017. The
      clinical examination was based on the World Health Organization criteria and a
      questionnaire was sent to parents or legal guardians to collect information on
      the children's food intake, pre-existing systemic diseases, medication use, and
      CMPA and LI. Standardization was performed to verify concordance among examiners
      (kappa = 0.96). Caries prevalence was 67.50% in children with CMPA or LI, but
      34.37% in those without these conditions. The mean dmft (decayed, missing, and
      filled teeth) index in children with CMPA or LI was 1.75 +/- 1.84, significantly
      higher than among non-allergic or lactose-tolerant children (0.83 +/- 1.60) (p <
      0.001). In children with CMPA or LI, the mean for treatment needs was 1.58 +/-
      1.50. Lactose-free milk was the most frequently consumed food among
      allergic/intolerant children (65.00%), with a mean dmft of 2.00 +/- 2.08, higher
      than that obtained for those without CMPA/LI (0.82 +/- 0.87), showing no
      significant difference (p = 0.129). Although dental caries and treatment needs in
      primary dentition were associated with CMPA or LI, children's intake of
      replacement foods did not pose any risk for the development of carious lesions.
      Statistically significant differences were obtained for the prevalence and
      severity of dental caries. This shows the need for treatment of children with
      CMPA or LI, who had the worst caries prevalence and severity rates.

PMID- 30231173
TI  - Hyaluronic acid accelerates bone repair in human dental sockets: a randomized
      triple-blind clinical trial.
AB  - This study evaluated the effects of hyaluronic acid (HA) on bone repair of human
      dental sockets. Thirty-two lower first premolars were extracted from 16 patients
      (2 per patient) for orthodontic reasons. Following the extractions, one socket
      was randomly filled with 1% HA gel, while the other was allowed to naturally fill
      with blood clot. After 30 and 90 days of surgery, patients underwent cone beam
      computed tomography. Five central orthoradial slices were captured from each
      socket. The gray intensity was measured in each image and results were reported
      as mean percentage of bone formation. The buccolingual alveolar ridge width was
      measured and dimensional changes were compared between the postoperative
      intervals. The pattern of alveolar trabecular bone was evaluated through the
      fractal dimension. Treated sockets showed a higher percentage of bone formation
      and fractal dimension values (58.17% and 1.098, respectively) compared with
      controls (48.97% and 1.074, respectively) in the 30-day postoperative period (p <
      0.05). After 90 days, there was no significant difference between groups.
      Additionally, no significant difference was found between groups regarding the
      alveolar dimensions (p > 0.05). Use of 1% HA gel after tooth extraction
      accelerates bone repair in human dental sockets.

PMID- 30231174
TI  - Evaluation of the efficacy of filling material removal and re-filling after
      different retreatment procedures.
AB  - This study analyzed the influence of different retreatment protocols on amount of
      remaining filling material and amount of new sealer after endodontic retreatment.
      Forty mandibular molars with curved mesial roots were prepared with ProTaper
      Universal system, and filled with AH Plus sealer mixed with 0.1% rhodamine B and
      gutta-percha. After 7 days, the specimens were randomized according to the
      retreatment protocol (n = 10): ProTaper Retreatment System (PTR); PTR+Orange Oil
      (PTR+OO); PTR+Passive Ultrasonic Irrigation (PTR+PUI). No retreatment was
      performed in the control group (CG). After retreatment, the root canals were
      filled with AH Plus mixed with 0.1% fluorescein and gutta-percha. Samples were
      evaluated under confocal laser scanning microscopy and analyzed using Image J
      software. Data were analyzed using Kruskal-Wallis and Dunn tests (p < 0.05).
      Regarding presence of residual filling, the Kruskal-Wallis test indicated no
      differences among the different retreatment techniques in the perimeter and the
      isthmus analyses (p > 0.05); however, PTR+PUI was associated with a lesser amount
      of residual filling material in the canal area analysis (p < 0.05). In evaluating
      the new filling, the perimeter analysis showed a lesser amount of new endodontic
      sealer in the PTR group (p < 0.05). Moreover, the PTR+PUI group presented a
      significantly greater amount of new endodontic sealer in the canal area analysis
      (p < 0.05). There was no difference among groups in the isthmus analysis (p >
      0.05). It can be concluded that PTR associated to PUI yielded better results in
      removing root canal filling material from the canal area. However, none of the
      protocols resulted in root walls completely free of remnants.

PMID- 30231177
TI  - Surgical Management of Nystagmus.

PMID- 30231175
TI  - Expression of urokinase-type plasminogen activator and its receptor in squamous
      cell carcinoma of the oral tongue.
AB  - Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) act in the
      proteolysis of basement membrane and extracellular matrix structures,
      facilitating tumor invasion. The purpose of this study was to evaluate the
      relationship between these proteins and clinicopathological parameters in
      squamous cell carcinoma of the oral tongue (SCCOT). Sixty cases of SCCOT were
      submitted to immunohistochemistry and analyzed semiquantitatively at the invasion
      front and in the tumor core. The results were associated with lymph node
      metastasis, clinical stage, locoregional recurrence, clinical outcome and
      histological grade of malignancy. A higher expression of uPA was observed in
      cases of tumors of high-grade versus low-grade malignancy (p = 0.010). Moreover,
      the cases with the worst pattern of invasion presented an overexpression of uPA
      (p = 0.011). The presence of locoregional recurrence was associated with uPAR (p
      = 0.039), and the expression of both biomarkers was much higher at the invasion
      front than in the tumor core (p < 0.001). The results suggest uPA and uPAR are
      involved in the progression and aggressiveness of SCCOT, mainly at the tumor-host
      interface.

PMID- 30231176
TI  - Short implants versus longer implants with maxillary sinus lift. A systematic
      review and meta-analysis.
AB  - This study compared the survival rate of dental implants, amount of marginal bone
      loss, and rates of complications (biological and prosthetic) between short
      implants and long implants placed after maxillary sinus augmentation. This
      systematic review has been registered at PROSPERO under the number
      (CRD42017073929). Two reviewers searched the PubMed/MEDLINE, Embase, LILACS, and
      Cochrane Library databases. Eligibility criteria included randomized controlled
      trials, comparisons between short implants and long implants placed after
      maxillary sinus augmentation in the same study, and follow-up for >6 months. The
      Cochrane Collaboration's tool for assessing the risk of bias in randomized trials
      was used to assess the quality and risk of bias of the included studies. The
      search identified 1366 references. After applying the inclusion criteria, 11
      trials including 420 patients who received 911 dental implants were considered
      eligible. No significant difference was observed in the survival rate [p = 0.86;
      risk ratio (RR): 1.08; 95% confidence interval (CI): 0.46-2.52] or in the amount
      of marginal bone loss (p = 0.08; RR: -0.05; 95%CI: -0.10 to 0.01). However,
      higher rates of biological complications for long implants associated with
      maxillary sinus augmentation were observed (p < 0.00001; RR: 0.21; 95%CI: 0.10
      0.41), whereas a higher prosthetic complication rate for short implants was noted
      (p = 0.010; RR: 3.15; 95%CI: 1.32-7.51). Short implant placement is an effective
      alternative because of fewer biological complications and similar survival and
      marginal bone loss than long implant placement with maxillary sinus augmentation.
      However, the risk of mechanical complications associated with the prostheses
      fitted on short implants should be considered.

PMID- 30231178
TI  - I Have a Bump.

PMID- 30231179
TI  - Light Come Shining: Fundus Autofluorescence.

PMID- 30231180
TI  - Macula Damage From Laser Pointers.

PMID- 30231181
TI  - Temporal Macular Pulsation During Retinopathy of Prematurity Screening.

PMID- 30231182
TI  - Aicardi Syndrome.

PMID- 30231183
TI  - Early Career Reflections: Observations From the First 5 Years in Practice.

PMID- 30231184
TI  - The Conservative Treatment of Osteoarthritis of the Knee.
AB  - Osteoarthritis has one of the highest associations for all-cause mortality in the
      United States. Comorbidities are common in patients with end-stage disease. In
      most cases, it is critical to exhaust conservative modalities of care before
      resorting to surgical intervention. This article discusses common conservative
      approaches focusing on injectable treatments that can be employed prior to total
      knee replacement. [Orthopedics. 2018; 41(5):256-260.].

PMID- 30231185
TI  - Discrete and Polymeric Self-Assembled Palladium(II) Complexes as Supramolecular
      Gelators.
AB  - Supramolecular gels prepared from low-molecular-weight gelators have been
      extensively explored. However, the exploitation of discrete or polymeric metal
      complexes as gelators is a relatively recent trend. The synthesis of self
      assembled coordination complexes from palladium(II) and selected ligands is well
      established, but the potential of these complexes as gelators is a less explored
      treasure. Herein we focus on the gelation abilities of some self-assembled
      palladium(II) complexes and the resulting unique properties. First, discrete
      complexes with PdL, PdL2 , Pd2 L, Pd2 L2 , Pd2 L4 , and Pd3 L6 compositions are
      discussed. Second, gelation behavior promoted by coordination-polymer-like
      gelators formed in situ is explored. These gel samples have been employed in
      catalysis and the uptake of organic and dye molecules from the solution and gas
      phases. It is concluded that untapped unique properties can be realized by
      further exploration of designer palladium(II) complexes.

PMID- 30231186
TI  - Chemoproteomic Profiling of Phosphoaspartate Modifications in Prokaryotes.
AB  - Phosphorylation at aspartic acid residues represents an abundant and critical
      post-translational modification (PTM) in prokaryotes. In contrast to most
      characterized PTMs, such as phosphorylation at serine or threonine, the
      phosphoaspartate moiety is intrinsically labile, and therefore incompatible with
      common proteomic profiling methods. Herein, we report a nucleophilic,
      desthiobiotin-containing hydroxylamine (DBHA) chemical probe that covalently
      labels modified aspartic acid residues in native proteomes. DBHA treatment
      coupled with LC-MS/MS analysis enabled detection of known phosphoaspartate
      modifications, as well as novel aspartic acid sites in the E. coli proteome.
      Coupled with isotopic labelling, DBHA-dependent proteomic profiling also
      permitted global quantification of changes in endogenous protein modification
      status, as demonstrated with the detection of increased E. coli OmpR
      phosphorylation, but not abundance, in response to changes in osmolarity.

PMID- 30231188
TI  - Associations between imprinted gene differentially methylated regions, appetitive
      traits and body mass index in children.
AB  - BACKGROUND: Knowledge regarding genetic influences on eating behaviours is
      expanding; yet less is known regarding contributions of epigenetic variation to
      appetitive traits and body mass index (BMI) in children. OBJECTIVE: The purpose
      of this study was to explore relationships between methylation at differentially
      methylated regions (DMRs) of imprinted genes (insulin-like growth factor 2/H19
      and Delta-like, Drosophila, homolog 1/maternally expressed gene 3) using DNA
      extracted from umbilical cord blood leucocytes, two genetically influenced
      appetitive traits (food responsiveness and satiety responsiveness) and BMI.
      METHODS: Data were obtained from participants (N = 317; mean age = 3.6 years; SD
      = 1.8 years) from the Newborn Epigenetic STudy. Conditional process models were
      implemented to investigate the associations between DMRs of imprinted genes and
      BMI, and test whether this association was mediated by appetitive traits and
      birthweight and moderated by sex. RESULTS: Appetitive traits and birthweight did
      not mediate the relationship between methylation at DMRs. Increased insulin-like
      growth factor 2 DMR methylation was associated with higher satiety
      responsiveness. Higher satiety responsiveness was associated with lower BMI.
      Associations between methylation at DMRs, appetitive traits and BMI differed by
      sex. CONCLUSIONS: This is one of the first studies to demonstrate associations
      between epigenetic variation established prior to birth with appetitive traits
      and BMI in children, providing support for the need to uncover genetic and
      epigenetic mechanisms for appetitive traits predisposing some individuals to
      obesity.

PMID- 30231189
TI  - Energy expenditure of household activities and cardiorespiratory fitness in women
      with obesity.

PMID- 30231187
TI  - Aronia (Aronia melanocarpa) Polyphenols Modulate the Microbial Community in a
      Simulator of the Human Intestinal Microbial Ecosystem (SHIME) and Decrease
      Secretion of Proinflammatory Markers in a Caco-2/endothelial Cell Coculture
      Model.
AB  - SCOPE: To explore the mechanisms behind the health effects of Aronia (Aronia
      melanocarpa), the microbial community modulating and anti-inflammatory effects of
      Aronia polyphenols are investigated by combining the similutor of the human
      intestinal microbial ecosystem (SHIME) with a coculture of intestinal and
      endothelial cells. RESULTS: Administration of Aronia juice (6.5g L-1 ) to the
      SHIME for 2 weeks increases the abundance of firmicutes to 92% in the ascending
      colon (AC), 85% in the transverse colon (TC), and 82% in the descending colon
      (DC; p < 0.001), proteobacteria (6.7% in AC, p < 0.001), and Akkermansia (14% in
      TC and 18% in DC, p < 0.001) and decreases the abundance of Bifidobacterium
      species, associated with a decrease of acetate and increase of propionate and
      butyrate, whereas no significant difference is observed upon placebo juice
      treatment. After addition of the digests to TNF-alpha challenged Caco
      2/endothelial cocultures, intercellular adhesion molecule (ICAM)-1, IL-8, and
      monocyte chemoattractant protein-1 levels are significantly downregulated.
      Interestingly, Aronia juice treats digests from each colon compartment resulting
      in a stronger decrease of the ICAM-1 secretion (up to 73%, p < 0.001) compared to
      their corresponding placebo treated digests, thereby pointing to a polyphenol
      dependent effect. CONCLUSIONS: Aronia polyphenols modulate intestinal microbial
      composition, induce beneficial short chain fatty acid production, and prevent
      inflammatory stress in endothelial cells. This opens perspectives for the use of
      Aronia polyphenols as prebiotics in the context of intestinal and cardiovascular
      health.

PMID- 30231190
TI  - "Then you raise them with Shirchoy or cookies": Understanding influences on
      delayed dietary diversity among children in Tajikistan.
AB  - Dietary diversity is a key component of infant and young child feeding (IYCF) as
      well as adult health. In Tajikistan, a predominantly rural, former Soviet country
      in Central Asia, we conducted formative research to identify barriers to dietary
      diversity and strategies for nutrition behaviour change. In Spring, 2016, mixed
      methods data collection took place across 13 villages in all five regions,
      collecting collaborative mapping; structured assessments of stores and markets;
      home visits for dietary recalls; food storage, preparation, and meal
      observations; focus groups with pregnant women, mothers of young children,
      fathers, and mothers-in-law; and in-depth expert interviews with local nutrition
      and health influentials. Overall, maternal diet was adequate in terms of
      diversity (only 13% reported <5/10 food groups in the past 24 hr); however, only
      42% of index children 6-24 months met WHO guidelines for diversity, and only 34%
      met minimum acceptable diet criteria. In addition to issues of poverty and food
      scarcity, qualitative data reveal many behavioural barriers to timely
      introduction of diverse complementary foods. Women's strategies focused on
      gradual introduction of household diet components, without regard for diversity
      or nutrition. Foods such as meat were seen as costly and thus inappropriate for
      IYCF, and food taboos (i.e., fresh vegetables) further reduced diversity. Infant
      food preparation methods such as grinding were seen as impractical, and many
      foods were withheld until children develop teeth. Possible nutrition education
      strategies include point-of-purchase campaigns to improve availability and appeal
      of IYCF-friendly foods, as well as influencing other key household members
      through mosques, schools, and health care providers.

PMID- 30231191
TI  - Corrigendum.

PMID- 30231192
TI  - Multipurpose Energetic Materials by Shuffling Nitro Groups on a 3,3'-Bipyrazole
      Moiety.
AB  - A family of 3,3'-bipyrazole-based energetic compounds having C-NO2 /N-NO2
      functionalities was synthesized by using various nitrating conditions. These
      nitro derivatives of bipyrazole are significantly more dense and energetic
      compared to the corresponding nitropyrazole analogues while maintaining the
      desired thermal stability and sensitivity. Depending on the number and nature of
      energetic nitro groups (C-NO2 /N-NO2 ), different classes of energetic materials,
      such as green primary explosives, high-performance secondary explosives and heat
      resistant explosives, were obtained. All the compounds were thoroughly
      characterized by IR, NMR [1 H, 13 C{1 H}, 15 N], elemental analysis, and
      differential scanning calorimetry (DSC). Four were also structurally
      characterized with single-crystal X-ray diffraction studies. Heats of formation
      and detonation performance were calculated using Gaussian 03 and EXPLO5 v6.01
      programs, respectively.

PMID- 30231193
TI  - 3D task-transfer function representation of the signal transfer properties of low
      contrast lesions in FBP- and iterative-reconstructed CT.
AB  - PURPOSE: The purpose of this study was to investigate how accurately the task
      transfer function (TTF) models the signal transfer properties of low-contrast
      features in a non-linear commercial CT system. METHODS: A cylindrical phantom
      containing 24 anthropomorphic "physical" lesions was 3D printed. Lesions had two
      sizes (523, 2145 mm3 ), and two nominal radio-densities (80 and 100 HU at 120
      kV). CT images were acquired on a commercial CT system (Siemens Flash scanner) at
      four dose levels (CTDIvol , 32 cm phantom:1.5, 3.0, 6.0, 22.0 mGy) and
      reconstructed using FBP and IR kernels (B31f, B45f, I31f?2, I44f?2). Low-contrast
      rod inserts (in-plane) and a slanted edge (z-direction) were used to estimate 3D
      TTFs. CAD versions of lesions were blurred by the 3D-TTFs, virtually superimposed
      into corresponding phantom images, and compared to the physical lesions in terms
      of (a) a 4AFC visual assessment, (b) edge gradient, (c) size, and (d) shape
      similarity. Assessments 2 and 3 were based on an equivalence criterion  RESULTS:
      The readers detected simulated lesions at a rate of 37.9 +/- 3.1% (25% implies
      random guessing). Lesion edge blur and volume differences  CONCLUSIONS: The
      visual appearance, edge blur, size, and shape of simulated lesions were similar
      to the physical lesions, which suggests 3D-TTF models the low-contrast signal
      transfer properties of this non-linear CT system reasonably well.

PMID- 30231194
TI  - Detection and genotyping of enteric viruses in hospitalized children with acute
      gastroenteritis in Belem, Brazil: Occurrence of adenovirus viremia by species F,
      types 40/41.
AB  - Enteric adenovirus (AdV), sapovirus (SaV), and human astrovirus (HAstV) are
      important pathogens involved in the gastroenteritis etiology. In this study, a
      total of 219 fecal samples and sera were collected from children hospitalized for
      acute gastroenteritis (AGE) in two large pediatric hospitals in Belem, from March
      2012 to April 2015. The samples were analyzed by polymerase chain reaction (PCR)
      for AdV and HAstV (astrovirus) detection, and Nested-PCR and qPCR for SaV
      detection. AdV was detected in 50.2% (110/219) of the cases, with 42.7% (47/110)
      being sequenced and classified as: species F (63.9% - 30/47), A (4.2% - 2/47), B
      (6.4% - 3/47), C (17.1% - 8/47), D (4.2% - 2/47), and E (4.2% - 2/47). Of the 110
      AdV-positive feces samples, 80 paired sera presented sufficient amounts and were
      also tested for this virus, of which 51 (63.7%) showed positive results and 26
      (70.3%) pairs (feces plus sera) presented concordant results after sequencing
      being classified as: species F (21/26; 80.8%), A (1/26; 3.8%), B (1/26; 3.8%),
      and C (3/26; 11.5%). Overall, HAstV rate in the feces samples was 1.8% (4/219),
      including both HAstV-1a (2/4; 50%) and HAstV-2c (2/4; 50%). SaV was detected in
      4.6% (10/219) of the fecal samples, out of which 50% (5/10) of the positive
      samples were characterized into the genogroups GI.1 (1), GI.2 (2), and GII.4 (2).
      These findings highlighted the important contributions of AdV, HAstV, and SaV in
      the enteric virus spectrum in our region and showed the high genetic diversity of
      AdV. In addition, it demonstrated for the first time in Brazil, the circulation
      of AdV in the serum of hospitalized children with AGE.

PMID- 30231195
TI  - Metabolic GWAS-based dissection of genetic bases underlying the diversity of
      plant metabolism.
AB  - Plants have served as sources providing humans with metabolites for food and
      nutrition, biomaterials for living, and treatment for pain and disease. Plants
      produce a huge array of metabolites, with an immense diversity at both the
      population and individual levels. Dissection of the genetic bases for metabolic
      diversity has attracted increasing research attention. The concept of genome-wide
      association study (GWAS) was extended to studies on the diversity of plant
      metabolome that benefitted from the development of mass-spectrometry-based
      analytical systems and genome sequencing technologies. Metabolic genome-wide
      association study (mGWAS) is one of the most powerful tools for global
      identification of genetic determinants for diversity of plant metabolism.
      Recently, mGWAS has been performed for various species with continuous
      improvements, providing deeper insights into the genetic bases of metabolic
      diversity. In this review, we discuss fully the achievements to date and
      remaining challenges that are associated with both mGWAS and mGWAS-based multi
      dimensional analysis. We begin with a summary of GWAS and its development based
      on statistical methods and populations. As variation in targeted traits is
      essential for GWAS, we review metabolic diversity and its rise at both the
      population and individual levels. Subsequently, the application of mGWAS for
      plants and its corresponding achievements are fully discussed. We address the
      current knowledge on mGWAS-based multi-dimensional analysis and emerging insights
      into the diversity of metabolism.

PMID- 30231196
TI  - Biochemical characteristics of a nitroreductase with diverse substrate
      specificity from Streptomyces mirabilis DUT001.
AB  - A nitroreductase-encoded gene from an efficient nitro-reducing bacterium
      Streptomyces mirabilis DUT001, named snr, was cloned and heterogeneously
      expressed in Escherichia coli. The purified Streptomyces nitroreductase SNR was a
      homodimer with an apparent subunit molecular weight of 24 kDa and preferred NADH
      to NADPH as a cofactor. By enzyme incubation and isothermal calorimetry
      experiments, flavin mononucleotide (FMN) was found to be the preferred flavin
      cofactor; the binding process was exothermic and primarily enthalpy driven. The
      enzyme can reduce multiple nitro compounds and flavins, including antibacterial
      drug nitrofurazone, priority pollutants 2,4-dinitrotoluene and 2,4,6
      trinitrotoluene, as well as key chemical intermediates 3-nitrophthalimide, 4
      nitrophthalimide, and 4-nitro-1,8-naphthalic anhydride. Among the substrates
      tested, the highest activity of kcat(app) /Km(app) (0.234 MUM-1  Sec-1 ) was
      observed for the reduction of FMN. Multiple sequence alignment revealed that the
      high FMN reduction activity of SNR may be due to the absence of a helix,
      constituting the entrance to the substrate pocket in other nitroreductases.

PMID- 30231197
TI  - Noncovalent Pyrene-Polyethylene Glycol Coatings of Carbon Nanotubes Achieve in
      Vitro Biocompatibility.
AB  - Single-walled carbon nanotubes (SWNTs) have become increasingly exploited in
      biological applications, such as imaging and drug delivery. The application of
      SWNTs in biological settings requires the surface chemistry to remain through the
      low solubility in aqueous media. In this research, a facile approach for the
      preparation of a polyethylene glycol (PEG)-coated SWNT-based nanocarrier was
      reported. We focused on the effect of PEG chain length and SWNT size on the
      cytotoxicity of PEG-coated SWNTs as a superior drug delivery nanovector. First,
      all-atom molecular dynamics (MD) simulations were employed to explore the
      stability and behavior of SWNT/pyrene-PEG (SWNT/Pyr-PEG) structures at a
      molecular level that is not attainable with experiments. The MD studies revealed
      that (i) pi-pi stacking interactions between the pyrene bearing PEG molecules and
      SWNTs are maintained in bulky situations, regardless of PEG molecular weight or
      SWNT size; (ii) pyrene molecules diffuse over the SWNT surface without detaching;
      and (iii) both short and long dynamic Pyr-PEG chains have the capability of
      effectively coating the SWNT surface. In light of the simulations, noncovalent
      (pi-pi stacking) assemblies of SWNT/Pyr-PEG with different molecular weights of
      PEG ( Mw = 2000, 5000, and 12000) were successfully fabricated and characterized.
      For longer PEG chains, more effective coating of SWNTs was obtained, resulting in
      more biocompatible SWNT/Pyr-PEG nanomaterials. The number of SWNTs coated by Pyr
      PEG was highly dependent on the length of pyrene bearing PEG polymers. Moreover,
      the short SWNTs showed a higher amount of PEG coating with respect to the long
      SWNTs. Cell viability results demonstrated a dose-dependent cytotoxicity of
      coated SWNTs. Short SWNTs coated with longer PEG chains have low cytotoxicity to
      be used in in vivo studies.

PMID- 30231198
TI  - Crystal Structures of Candida albicans Phosphodiesterase 2 and Implications for
      Its Biological Functions.
AB  - The cAMP signaling system plays important roles in the physiological processes of
      pathogen yeast Candida albicans, but its functional mechanism has not been well
      illustrated. Here, we report the enzymatic characterization and crystal
      structures of C. albicans phosphodiesterase 2 (caPDE2) in the unliganded and 3
      isobutyl-1-methylxanthine-complexed forms. caPDE2 is a monomer in liquid and
      crystal states and specifically hydrolyzes cAMP with a KM of 35 nM. It does not
      effectively hydrolyze cGMP as shown by the 1.32 * 105-fold specificity of
      cAMP/cGMP. The crystal structure of caPDE2 shows significant differences from
      those of human PDEs. First, the N-terminal fragment of caPDE2 (residues 1-201)
      tightly associates with the catalytic domain to form a rigid molecular entity,
      implying its stable molecular conformation for C. albicans to resist
      environmental stresses. Second, the M-loop, a critical fragment for binding of
      the substrate and inhibitors to human PDEs, is not a part of the caPDE2 active
      site. This feature of caPDE2 may provide a structural basis for the design of
      selective inhibitors for the treatment of yeast infection.

PMID- 30231199
TI  - H2 Oxidation over Supported Au Nanoparticle Catalysts: Evidence for Heterolytic
      H2 Activation at the Metal-Support Interface.
AB  - Water adsorbed at the metal-support interface (MSI) plays an important role in
      multiple reactions. Due to its importance in CO preferential oxidation (PrOx), we
      examined H2 oxidation kinetics in the presence of water over Au/TiO2 and Au/Al2O3
      catalysts, reaching the following mechanistic conclusions: (i) O2 activation
      follows a similar mechanism to that proposed in CO oxidation catalysis; (ii)
      weakly adsorbed H2O is a strong reaction inhibitor; (iii) fast H2 activation
      occurs at the MSI, and (iv) H2 activation kinetics are inconsistent with
      traditional dissociative H2 chemisorption on metals. Density functional theory
      (DFT) calculations using a supported Au nanorod model suggest H2 activation
      proceeds through a heterolytic dissociation mechanism, resulting in a formal
      hydride residing on the Au and a proton bound to a surface TiOH group. This
      potential mechanism was supported by infrared spectroscopy experiments during H2
      adsorption on a deuterated Au/TiO2 surface, which showed rapid H-D scrambling
      with surface hydroxyl groups. DFT calculations suggest that the reaction proceeds
      largely through proton-mediated pathways and that typical Bronsted-Evans Polanyi
      behavior is broken by introducing weak acid/base sites at the MSI. The kinetics
      data were successfully reinterpreted in the context of the heterolytic H2
      activation mechanism, tying together the experimental and computational evidence
      and rationalizing the observed inhibition by physiorbed water on the support as
      blocking the MSI sites required for heterolytic H2 activation. In addition to
      providing evidence for this unusual H2 activation mechanism, these results offer
      additional insight into why water dramatically improves CO PrOx catalysis over
      Au.

PMID- 30231200
TI  - Shape-Transformable, Fusible Rodlike Swimming Liquid Metal Nanomachine.
AB  - The T-1000 liquid metal terminator, which can transform and self-repair,
      represents a dream for decades that robots can fundamentally change our daily
      life. Until now, some large-scale liquid metal machines have been developed.
      However, there is no report on nanoscaled liquid metal machines and their
      biomedical applications. We describe here a shape-transformable and fusible
      rodlike swimming liquid metal nanomachine, based on the biocompatible and
      transformable liquid metal gallium. These nanomachines were prepared by a
      pressure-filter-template technology, and the diameter and length could be
      controlled by adjusting the nanoporous templates, filter time, and pressure. The
      as-prepared liquid gallium nanomotors display a core-shell nanorod structure
      composed of a liquid gallium core and solid gallium oxide shell. Upon exposure to
      an ultrasound field, the generated acoustic radiation force in the levitation
      plane can propel them to move autonomously. The liquid metal nanomachine can
      actively seek cancer cells and transform from a rod to a droplet after drilling
      into cells owing to the removal of gallium oxide layers in the acidic endosomes.
      These transformed nanomachines could fuse together inside cells and
      photothermally kill cancer cells under illumination of near-infrared light. Such
      acoustically propelled shape-transformable rodlike liquid metal nanomachines have
      great potential for biomedical applications.

PMID- 30231201
TI  - Zinc Coordinated Cationic Polymers Break Up the Paradox between Low Molecular
      Weight and High Transfection Efficacy.
AB  - Cationic polymers have emerged as appealing nonviral gene vectors for decades,
      which, however, suffer from the paradox between low molecular weight and high
      transfection efficacy. Low molecular weight cationic polymers (LCPs) are well
      cell tolerated but are perplexed by orders-of-magnitude less efficacy compared to
      their macromolecular counterparts. The deficiency mainly lies in weak DNA binding
      of polymers and difficulty in endosomal escape of formulated polyplexes. Herein,
      we demonstrate that, through zinc (Zn) coordinated modification of LCPs, the high
      transfection efficiency and low molecular weight (thus low cytotoxicity) can be
      achieved simultaneously. The Zn coordinated ligand shows a high affinity to
      phosphate components and therefore will largely benefit the DNA packaging and
      endosomal membrane destabilization, addressing the defects of LCPs in gene
      delivery. Zn coordinative functionalization of LCPs breaks up the "efficacy
      toxicity" paradox and provides great promise for the development of clinically
      efficient and safe nonviral gene vectors.

PMID- 30231202
TI  - Surface Plasmon Resonance Sensing on Naturally Derived Membranes: A Remyelination
      Promoting Human Antibody Binds Myelin with Extraordinary Affinity.
AB  - rHIgM22 is a recombinant human monoclonal IgM designed to promote remyelination,
      and it is currently in Phase I clinical trials in patients with multiple
      sclerosis (MS). In animal models of demyelination, a single low dose of rHIgM22
      stimulates oligodendrocyte maturation, induces remyelination, preserves axons,
      and slows the decline of locomotor deficits. Natural autoantibodies like rHIgM22
      typically bind to multiple antigens with weak affinity. rHIgM22 binds to
      oligodendrocytes and myelin. Because the antigens for rHIgM22 is prevalent within
      and exclusive to central nervous system (CNS) myelin, we used CNS myelin
      particles in combination with surface plasmon resonance to determine the kinetic
      and affinity constants for the interaction of rHIgM22 to myelin. We found that
      both the serum and recombinant forms of the antibody bind to myelin with very
      small dissociation constants in the 100 pM range, which is highly unusual for
      natural autoantibodies. The extraordinary affinity between rHIgM22 and myelin may
      explain why such a low effective dose can stimulate CNS repair in animal models
      of demyelination and underlie the accumulation of rHIgM22 in the CSF in treated
      MS patients by targeting myelin.

PMID- 30231204
TI  - Enhanced Skull Bone Regeneration by Sustained Release of BMP-2 in
      Interpenetrating Composite Hydrogels.
AB  - Direct administration of bone morphogenetic protein-2 (BMP-2) for bone
      regeneration could cause various clinical side effects such as osteoclast
      activation, inflammation, adipogenesis, and bone cyst formation. In this study,
      thiolated gelatin/poly(ethylene glycol) diacrylate (PEGDA) interpenetrating (IPN)
      composite hydrogels were developed for guided skull bone regeneration. To promote
      bone regeneration, either polycation-based coacervates (Coa) or gelatin
      microparticles (GMPs) were incorporated within IPN gels as BMP-2 carriers. Both
      BMP-2 loaded Coa and BMP-2 loaded GMPs showed significantly enhanced in vitro
      alkaline phosphate (ALP) activity of human mesenchymal stem cells (hMSCs) than
      non-BMP-2 treated control. Moreover, BMP-2 loaded GMPs group exhibited
      statistically increased ALP activity compared to both bolus BMP-2 administration
      and BMP-2 loaded Coa group, indicating that our carriers could protect and
      maintain biological activity of cargo BMP-2. Sustained release kinetics of BMP-2
      from IPN composite hydrogels could be controlled by different formulations. For
      in vivo bone regeneration, various IPN gel formulations (i.e., (1) control, (2)
      only hydrogel, (3) hydrogel with bolus BMP-2, (4) hydrogel with BMP-2-loaded Coa,
      and (5) hydrogel with BMP-2-loaded GMPs) were bilaterally implanted into 5 mm
      sized rat calvarial defects. After 4 weeks, micro-CT and histological analysis
      were performed to evaluate new bone formation. Significantly higher scores for
      bony bridging and union were observed in BMP-2-loaded Coa and BMP-2-loaded GMP
      groups as compared to other formulations. In addition, rats treated with BMP-2
      loaded GMPs showed a significantly higher ratio of bone volume/total volume and
      lower trabecular separation scores than others. Finally, rats treated with either
      Coa or GMP groups exhibited a significant increase in bone formation area, as
      assessed via histomorphometric analysis. Taken together, it could be concluded
      that Coa and GMPs were effective carriers to maintain the bioactivity of cargo
      BMP-2 during its sustained release. Consequently, our IPN composite hydrogel
      system that combines such BMP-2 carriers could effectively promote skull bone
      regeneration.

PMID- 30231203
TI  - Stromal Modulation Reverses Primary Resistance to Immune Checkpoint Blockade in
      Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers
      to treat. It is refractory to most existing therapies, including immunotherapies,
      due to the presence of an excessive desmoplastic stroma, which restricts
      penetration of drugs and cytotoxic CD8+ T cells. Stromal modulation has shown
      promising results in the enhancement of immune checkpoint blockade treatment in
      PDAC. We demonstrate here effective stromal modulation by a polymeric micelle
      based nanoformulation to codeliver a sonic hedgehog inhibitor (cyclopamine,
      abbreviated as CPA) and a cytotoxic chemotherapy drug (paclitaxel, abbreviated as
      PTX). The formulation, M-CPA/PTX, modulated the PDAC stroma by increasing the
      intratumoral vasculature density, which then promoted the tumor infiltration by
      cytotoxic CD8+ T cells without depletion of tumor-restraining alpha-smooth muscle
      action-positive fibroblasts and type I collage in the stroma. The combination of
      M-CPA/PTX and the PD-1 checkpoint blockade significantly prolonged animal
      survival in an orthotopic murine PDAC model as well as a genetically engineered
      mouse model of PDAC. The superior antitumor efficacy was mediated by enhanced
      tumor infiltration of CD8+ T cells without concomitant infiltration of
      suppressive regulatory T cells or myeloid-derived suppressor cells and by the
      coordinated action of PTX and interferon-gamma. Our results demonstrate that
      stroma-modulating nanoformulations are a promising approach to potentiate immune
      checkpoint blockade therapy of pancreatic cancer.

PMID- 30231205
TI  - Epitaxial Crystallization of Isotactic Poly(methyl methacrylate) from Different
      States on Highly Oriented Polyethylene Thin Film.
AB  - Through fixing the orientation of oriented polyethylene (PE) thin film during
      melt-recrystallization with the help of a vacuum evaporated thin carbon layer,
      the isothermal melt- and cold-crystallization of isotactic poly(methyl
      methacrylate) (iPMMA) on oriented PE substrate was studied. The results show that
      same parallel chain epitaxy of iPMMA on the oriented PE substrate takes place in
      both cold- and melt-crystallization processes based on a two-dimensional lattice
      matching. However, the crystallization kinetics in the two processes is quite
      different. The induction time of iPMMA during melt-crystallization is
      significantly longer than during cold-crystallization (11 h vs 2.5 h). This is
      related to the different nucleation mechanism for cold- and melt-crystallization
      processes. On the other hand, the crystal growth rate of iPMMA from melt is much
      higher than from glassy solid state. This is associated with a higher molecular
      chain mobility of iPMMA in supercooled melt than in the frozen amorphous solid
      film.

PMID- 30231206
TI  - Plasma-Deposited Nanocapsules Containing Coatings for Drug Delivery Applications.
AB  - Coatings consisting in gentamicin-containing nanocapsules have been synthetized
      by means of an aerosol-assisted atmospheric pressure plasma deposition process.
      The influence of different parameters affecting the process has been extensively
      investigated by means of a morphological and chemical characterization of the
      coatings. Scanning electron microscopy highlighted the presence of nanocapsules
      whose size and abundance depend on power input and deposition time. A detailed
      analysis carried out with matrix-assisted laser desorption ionization coupled to
      high-resolution mass spectrometry allowed to detect and identify the presence of
      gentamicin embedded in the coatings and its rearrangement, as a result of the
      interaction with the plasma. The release of gentamicin in water has been
      monitored by means of UV-vis fluorescence spectroscopy, and its biological
      activity has been evaluated as well by the disk diffusion assay against
      Staphylococcus aureus and Pseudomonas aeruginosa. It is confirmed that the
      antibacterial activity of gentamicin is preserved in the plasma-deposited
      coatings. Preliminary cytocompatibility investigations indicated that eukaryotic
      cells well tolerate the release of gentamicin from the coatings.

PMID- 30231207
TI  - Organophosphate Ester Transport, Fate, and Emissions in Toronto, Canada,
      Estimated Using an Updated Multimedia Urban Model.
AB  - Organophosphate esters (OPEs), used as flame retardants and plasticizers, occur
      at relatively high concentrations in urban air and surface waters. We tested the
      hypothesis that some OPEs could be considered persistent and mobile organic
      compounds (PMOCs), using the poly parameter linear free energy relationship
      modified Multimedia Urban Model (ppLFER-MUM) in Toronto, Canada, as a case study.
      Modeled air emissions of ?6OPEs of 3300 (190-190 000) kg yr-1 were 10-100 times
      higher than emissions of polychlorinated biphenyls (?5PCBs) and polybrominated
      diphenyl ethers (?5PBDEs). Model results suggested that measured ?6OPE stream
      concentrations of ~2000 ng L-1 originate from emissions to urban air transferred
      to water mostly via precipitation. Water transport removed 7-28% of total air
      inputs compared to 0.1-10% for PCBs and 2-10% for PBDEs. Chlorinated OPEs were
      efficiently transported via surface water due to their persistence and high
      solubility. Loadings of ?6OPEs to Lake Ontario from wastewater treatment plants,
      streams, and atmospheric deposition were 70%, 18%, and 13%, respectively, of
      ?6OPE loadings of 3100 (1200-45 000) kg yr-1. Our results support the hypothesis
      that three chlorinated OPEs, tris(2-chloroethyl)phosphate phosphate (TCEP),
      tris(chloroisopropyl)phosphate (TCiPP), and tris(1,3-dichloroisopropyl)phosphate
      (TDCiPP), fit the profile of PMOCs due to their mobility and persistence in
      surface waters.

PMID- 30231208
TI  - Thermoresponsive Gel Embedded with Adipose Stem-Cell-Derived Extracellular
      Vesicles Promotes Esophageal Fistula Healing in a Thermo-Actuated Delivery
      Strategy.
AB  - Extracellular vesicles (EVs) are increasingly envisioned as the next generation
      of biological pro-regenerative nanotherapeutic agents, as has already been
      demonstrated for heart, kidney, liver, and brain tissues; lung injury repair; and
      skin regeneration. Herein, we explore another potential EV therapeutic
      application, fistula healing, together with a local minimally invasive delivery
      strategy. Allogenic extracellular vesicles (EVs) from adipose tissue-derived
      stromal cells (ASCs) are administered in a porcine fistula model through a
      thermoresponsive Pluronic F-127 (PF-127) gel, injected locally at 4  degrees C
      and gelling at body temperature to retain EVs in the entire fistula tract.
      Complete fistula healing is reported to be 100% for the gel plus EVs group, 67%
      for the gel group, and 0% for the control, supporting the therapeutic use of
      Pluronic F-127 gel alone or combined with EVs. However, only the combination of
      gel and EVs results in a statistically significant (i) reduction of fibrosis,
      (ii) decline of inflammatory response, (iii) decrease in the density of
      myofibroblasts, and (iv) increase of angiogenesis. Overall, we demonstrate that
      ASC-EV delivery into a PF-127 gel represents a successful local minimally
      invasive strategy to induce a therapeutic effect in a swine fistula model. Our
      study presents prospects for EV administration strategies and for the management
      of post-operative fistulas.

PMID- 30231209
TI  - Multicompartmentalized Microreactors Containing Nuclei and Catalase-Loaded
      Liposomes.
AB  - Multicompartmentalized microreactors are considered as cell mimics with
      hierarchical structures inspired by mammalian cells. We report the successful
      assembly and encapsulation of purified nuclei from RAW 264.7 cells (pNuc) into
      alginate-based microreactors. We demonstrate the preserved function of nuclei
      within the microreactors for mRNA production. Further, we load catalase-loaded
      liposomes (Lcat) into the microreactors to break down hydrogen peroxide (H2O2)
      into oxygen and water. Assemblies containing both natural pNuc and synthetic Lcat
      show significantly higher mRNA production in the presence of H2O2 compared to
      microreactors without Lcat or no H2O2 present, suggesting a beneficial effect of
      the locally enzymatically produced oxygen for transcription. This novel type of
      microreactors, containing both natural and synthetic compartments, presents a
      substantial advancement from assemblies equipped with solely synthetic units and
      offers opportunities as hypoxia models or for cell-free protein synthesis.

PMID- 30231210
TI  - Hemostatic responses to exercise, dehydration, and simulated bleeding in heat
      stressed humans.
AB  - Heat stress followed by an accompanying hemorrhagic challenge may influence
      hemostasis. We tested the hypothesis that hemostatic responses are increased by
      passive heat stress, and exercise-induced heat stress, each with accompanying
      central hypovolemia to simulate a hemorrhagic insult. In Aim 1, subjects were
      exposed to passive heating or normothermic time control, each followed by
      progressive lower-body negative pressure (LBNP) to pre-syncope. In Aim 2 subjects
      exercised in hyperthermic environmental conditions, with and without accompanying
      dehydration, each also followed by progressive LBNP to pre-syncope. At baseline,
      pre-LBNP and post-LBNP, hemostatic activity of venous blood was evaluated by
      plasma markers of hemostasis and thrombelastography. For Aim 1, both hyperthermic
      and normothermic LBNP (H-LBNP and N-LBNP, respectively) resulted in higher levels
      of Factor V, Factor VIII, and vWF antigen compared to the time control trial (all
      P<0.05), but these responses were temperature independent. Hyperthermia increased
      fibrinolysis (LY30) to 5.1% post-LBNP, compared to 1.5% (time control) and 2.7%
      in N-LBNP (P=0.05 for main effect). Hyperthermia also potentiated increased
      platelet counts post-LBNP: 274(k/uL) for H-LBNP, 246(k/uL) for N-LBNP, 196(k/uL)
      for time control (P<0.05 for the interaction). For Aim 2, hydration status during
      exercise in the heat did not affect the hemostatic activity, but fibrinolysis
      (LY30) was increased to 6-10% when subjects were dehydrated compared to an
      increase to 2-4% when hydrated (P=0.05 for treatment). Central hypovolemia is a
      primary driver of hemostasis when compared to hyperthermia and dehydration.
      However, hyperthermia induces significant thrombocytosis and by itself causes an
      increase in clot lysis. Dehydration associated with exercise-induced heat stress
      increases clot lysis but does not affect exercise-activated or hypovolemia
      activated hemostasis in hyperthermic humans. Clinical implications of these
      findings are that quickly restoring a hemorrhaging hypovolemic trauma patient
      with cold, non-coagulant fluids (crystalloids) can have serious deleterious
      effects on the body's ability to form essential clots.

PMID- 30231212
TI  - JHL News.

PMID- 30231211
TI  - Another Look at WIC's Breastfeeding Data: State Totals Reveal More Than Regional
      Averages.
AB  - BACKGROUND: Breastfeeding is known to be the most beneficial way of feeding
      infants, but 68% of the infants enrolled in the U.S. Department of Agriculture's
      Special Supplemental Nutrition Program for Women, Infants, and Children are fully
      formula fed (FFF). Mandated annual reports about breastfeeding aggregate data
      from the states into regions, which obscures important information. Research Aim:
      The aim of this study is to reexamine the data supplied by the Special
      Supplemental Nutrition Program for Women, Infants, and Children to identify which
      areas of the United States have the lowest incidence of breastfeeding infants.
      METHODS: A retrospective cross-sectional observational study was conducted. Data
      from the Breastfeeding Data Local Agency Report were extracted, graphed, and
      analyzed. RESULTS: Data provided from the Special Supplemental Nutrition Program
      for Women, Infants, and Children for fiscal year 2016 show that the range of FFF
      infants at the regional level is 60% to 78%, while at the state level the range
      is wider, at 51% to 89%. The states with the largest numbers of FFF infants were
      Mississippi (89%), Louisiana (88%), Alabama (88%), and Arkansas (87%). When
      examining data from all 90 reporting agencies, the range of FFF infants was 38%
      to 95%. CONCLUSIONS: Aggregating state, Native American nation, and territorial
      data at the regional level resulted in a loss of important information. WIC's
      current breastfeeding interventions may be more effective in some areas than
      others. Future research can examine successful and unsuccessful interventions on
      a state or local level.

PMID- 30231213
TI  - Conspiracy Theories: Evolved Functions and Psychological Mechanisms.
AB  - Belief in conspiracy theories-such as that the 9/11 terrorist attacks were an
      inside job or that the pharmaceutical industry deliberately spreads diseases-is a
      widespread and culturally universal phenomenon. Why do so many people around the
      globe believe conspiracy theories, and why are they so influential? Previous
      research focused on the proximate mechanisms underlying conspiracy beliefs but
      ignored the distal, evolutionary origins and functions. We review evidence
      pertaining to two competing evolutionary hypotheses: (a) conspiracy beliefs are a
      by-product of a suite of psychological mechanisms (e.g., pattern recognition,
      agency detection, threat management, alliance detection) that evolved for
      different reasons, or (b) conspiracy beliefs are part of an evolved psychological
      mechanism specifically aimed at detecting dangerous coalitions. This latter
      perspective assumes that conspiracy theories are activated after specific
      coalition cues, which produce functional counterstrategies to cope with suspected
      conspiracies. Insights from social, cultural and evolutionary psychology provide
      tentative support for six propositions that follow from the adaptation
      hypothesis. We propose that people possess a functionally integrated mental
      system to detect conspiracies that in all likelihood has been shaped in an
      ancestral human environment in which hostile coalitions-that is, conspiracies
      that truly existed-were a frequent cause of misery, death, and reproductive loss.

PMID- 30231214
TI  - BFHI News Brief: The Baby-Friendly Hospital Initiative Network.

PMID- 30231215
TI  - Weight-Related Concerns as Barriers to Exclusive Breastfeeding at 6 Months.
AB  - BACKGROUND: Human milk is considered the gold standard for infant nutrition, but
      more data are needed that examine the constellation of weight-related concerns as
      barriers to exclusive breastfeeding. Research Aims: The aim of this study was to
      examine how mothers' concerns regarding their own and their infants' weight, as
      well as disordered eating behaviors, were associated with breastfeeding self
      efficacy and exclusive breastfeeding at 6 months. METHODS: A prospective,
      quantitative, and self-report online survey design was used. Participants
      included 206 women (88.30% White, 59.20% with graduate degrees), with a mean age
      of 33.04 years ( SD = 4.31 years) and a mean prepregnancy body mass index (BMI)
      of 24.80 kg/m2 ( SD = 5.50 kg/m2), who had given birth within the past 6 months.
      RESULTS: Participants who reported not exclusively breastfeeding at 6 months had
      significantly higher prepregnancy BMI ( p < .001), higher body dissatisfaction (
      p = .003), more disordered eating ( p = .036), higher child weight concerns ( p <
      .001), and lower breastfeeding self-efficacy ( p < .001). Mediation modeling
      revealed a direct negative relationship between prepregnancy BMI and exclusive
      breastfeeding at 6 months ( p < .001). Indirect negative relationships between
      prepregnancy BMI and exclusive breastfeeding at six months via (a) body
      dissatisfaction, (b) disordered eating, and (c) child weight concern, as well as
      breastfeeding self-efficacy (entered as concurrent mediators), were all
      significant. CONCLUSIONS: Mothers' weight, body image and eating concerns,
      concern regarding their children's weight, and breastfeeding self-efficacy may
      constitute critical barriers to exclusive breastfeeding at 6 months.
      Interventions to improve breastfeeding duration and confidence should target
      maternal body image and eating concerns.

PMID- 30231216
TI  - Therapeutic systemic hypothermia for a pediatric patient with an isolated
      cervical spinal cord injury.
AB  - CONTEXT: While uncommon, spinal cord injuries most frequently occur in adolescent
      and young adult males. Established treatment options are limited and focused on
      supportive care. Therapeutic systemic hypothermia is an emerging experimental
      treatment currently undergoing clinical trials in adults. FINDINGS: Here we
      report a case of a 13-year-old male with an American Spinal Injury Association
      Impairment Scale grade C traumatic cervical spinal cord injury treated with 48
      hours of therapeutic systemic hypothermia who made a complete neurological
      recovery. To our knowledge, this is the youngest such case report. CLINICAL
      RELEVANCE: This case suggests that consideration should be given to including
      pediatric patients in future clinical trials of therapeutic hypothermia for
      spinal cord injury.

PMID- 30231217
TI  - Black Nurse, White Milk: Breastfeeding, Slavery, and Abolition in 19th-Century
      Brazil.
AB  - Brazil imported more enslaved Africans than any other slave-owning society in the
      Americas, and it was the last country in the western hemisphere to abolish the
      institution. Whereas many enslaved persons toiled on plantations and in mines,
      urban slavery was also prominent, with enslaved men carrying coffee through the
      streets and enslaved women washing clothes. One gendered aspect of urban slavery
      in 19th-century Brazil included slave owners renting out enslaved women as wet
      nurses to breastfeed the children of elite families. This article reviews medical
      dissertations, debates, and journal articles, as well as advertisements for wet
      nurses, showing that physicians believed that enslaved women's milk was both
      nutritionally and morally inferior to white women's milk. In the latter half of
      the 19th century, physicians viewed abolition as the only answer to what they
      deemed the increasingly "dangerous" practice of enslaved wet nursing, which they
      believed was the root cause of high infant mortality rates across races and
      classes. Readers should consider the ethical dilemmas of the practice of enslaved
      wet nursing, which often resulted in the violent separation of mother and child.

PMID- 30231218
TI  - Graduate-entry medicine: a worthwhile innovation.

PMID- 30231219
TI  - Cultured Cells and ROCK Inhibitor for Bullous Keratopathy.

PMID- 30231220
TI  - The FDA Amendments Act of 2007 - Assessing Its Effects a Decade Later.

PMID- 30231221
TI  - Trends in Modern Phase 1 Oncology Trials.

PMID- 30231222
TI  - Doctoring while Sick - Is Living with Cancer Making Me a Better or Worse Doctor?

PMID- 30231223
TI  - Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

PMID- 30231225
TI  - Tuberculous Peritonitis.

PMID- 30231224
TI  - Variation in Childhood Diarrheal Morbidity and Mortality in Africa, 2000-2015.
AB  - BACKGROUND: Diarrheal diseases are the third leading cause of disease and death
      in children younger than 5 years of age in Africa and were responsible for an
      estimated 30 million cases of severe diarrhea (95% credible interval, 27 million
      to 33 million) and 330,000 deaths (95% credible interval, 270,000 to 380,000) in
      2015. The development of targeted approaches to address this burden has been
      hampered by a paucity of comprehensive, fine-scale estimates of diarrhea-related
      disease and death among and within countries. METHODS: We produced annual
      estimates of the prevalence and incidence of diarrhea and diarrhea-related
      mortality with high geographic detail (5 km2) across Africa from 2000 through
      2015. Estimates were created with the use of Bayesian geostatistical techniques
      and were calibrated to the results from the Global Burden of Diseases, Injuries,
      and Risk Factors Study 2016. RESULTS: The results revealed geographic inequality
      with regard to diarrhea risk in Africa. Of the estimated 330,000 childhood deaths
      that were attributable to diarrhea in 2015, more than 50% occurred in 55 of the
      782 first-level administrative subdivisions (e.g., states). In 2015, mortality
      rates among first-level administrative subdivisions in Nigeria differed by up to
      a factor of 6. The case fatality rates were highly varied at the national level
      across Africa, with the highest values observed in Benin, Lesotho, Mali, Nigeria,
      and Sierra Leone. CONCLUSIONS: Our findings showed concentrated areas of
      diarrheal disease and diarrhea-related death in countries that had a consistently
      high burden as well as in countries that had considerable national-level
      reductions in diarrhea burden. (Funded by the Bill and Melinda Gates
      Foundation.).

PMID- 30231226
TI  - Ivosidenib in IDH1-Mutated Acute Myeloid Leukemia.

PMID- 30231227
TI  - Sodium Thiosulfate and Cisplatin-Induced Hearing Loss.

PMID- 30231228
TI  - Prevalence of Self-Reported Head Injury in the United States.

PMID- 30231229
TI  - Case 29-2018: A 31-Year-Old Woman with Infertility.

PMID- 30231230
TI  - Systemic AA Amyloidosis Caused by Inflammatory Hepatocellular Adenoma.

PMID- 30231231
TI  - Atezolizumab Treatment of Nonsquamous NSCLC.

PMID- 30231232
TI  - Antibody-Mediated Rejection of Solid-Organ Allografts.

PMID- 30231233
TI  - Tuberculosis of the Finger.

PMID- 30231234
TI  - Occupational and Take-home Lead Exposure Among Lead Oxide Manufacturing
      Employees, North Carolina, 2016.
AB  - OBJECTIVE:: In 2016, North Carolina blood lead level (BLL) surveillance
      activities identified elevated BLLs among 3 children exposed to take-home lead by
      household members employed at a lead oxide manufacturing facility. We
      characterized BLLs among employees and associated children and identified risk
      factors for occupational and take-home lead exposure. METHODS:: We reviewed BLL
      surveillance data for 2012-2016 to identify facility employees and associated
      children. We considered a BLL >=5 MUg/dL elevated for adults and children and
      compared adult BLLs with regulatory limits and recommended health-based
      thresholds. We also conducted an environmental investigation and interviewed
      current employees about exposure controls and cleanup procedures. RESULTS::
      During 2012-2016, 5 children associated with facility employees had a confirmed
      BLL >=5 MUg/dL. Among 77 people employed during 2012-2016, median BLLs increased
      from 22 MUg/dL (range, 4-45 MUg/dL) in 2012 to 37 MUg/dL (range, 16-54 MUg/dL) in
      2016. All employee BLLs were <60 MUg/dL, the national regulatory threshold for
      immediate medical removal from lead exposure; however, 55 (71%) had a BLL >=20
      MUg/dL, a recommended health-based threshold for removal from lead exposure.
      Because of inadequate controls in the facility, areas considered clean were
      visibly contaminated with lead dust. Employees reported bringing personal items
      to work and then into their cars and homes, resulting in take-home lead exposure.
      CONCLUSIONS:: Integration of child and adult BLL surveillance activities
      identified an occupational source of lead exposure among workers and associated
      children. Our findings support recent recommendations that implementation of
      updated lead standards will support better control of lead in the workplace and
      prevent lead from being carried home.

PMID- 30231235
TI  - Head-to-Head Comparison of Modified Laparoscopic Pyeloplasty and Robot-Assisted
      Pyeloplasty for Ureteropelvic Junction Obstruction in China.
AB  - OBJECTIVE: To compare the outcomes of modified laparoscopic pyeloplasty (LP) and
      robot-assisted pyeloplasty (RLP) for ureteropelvic junction obstruction (UPJO) in
      China patients. MATERIALS AND METHODS: We retrospectively reviewed the medical
      records of patients who underwent modified LP and RLP using a transperitoneal
      laparoscopic approach at 2 different medical institutions between October 2009
      and November 2017. RESULTS: Seventy-six patients underwent modified LP and 140
      patients underwent RLP. No open conversion occurred. The mean operative time of
      RLP was shorter than that of modified LP (p = 0.042). For UPJO concomitant with
      renal calculi, there was no difference in operative time between 2 groups (p =
      0.656). With RLP, the operative time for UPJO concomitant with horseshoe was
      shorter (p = 0.011). In terms of complication rate, there was no significant
      difference between 2 groups (p = 0.596). The postoperative hospital stay for
      modified LP was shorter than that for RLP (p < 0.05). The mean follow-up time for
      modified LP and RLP was 31.79 months and 10.85 months respectively (p < 0.05).
      The success rate was 96.05 and 97.86% for modified LP and RLP, respectively (p =
      0.736). CONCLUSIONS: Modified LP and RLP are safe and efficient treatment for
      UPJO with similar success rates.

PMID- 30231236
TI  - Effects of Ghrelin on iNOS-Derived NO Promoted LPS-Induced Pulmonary Alveolar
      Epithelial A549 Cells Apoptosis.
AB  - BACKGROUND/AIMS: In the process of abnormal apoptosis of pulmonary alveolar type
      II epithelial A549 cells in acute respiratory distress syndrome (ARDS), inducible
      nitric oxide synthase (iNOS) activity in the lung, nitric oxide (NO) production,
      and the level of protein S-nitrosylation were increased. However, the role of
      excessive NO production in sepsis-induced ARDS is controversial. Additionally,
      ghrelin is a growth hormone that exerts an inhibitory role in cell apoptosis. We
      examined the effect of NO and S-nitrosylation on apoptosis of A549 cells induced
      by Lipopolysaccharide (LPS) and molecular mechanism underlying the anti-apoptotic
      effect of ghrelin in this process. METHODS: Flow cytometry and qPCR were used to
      detect lentiviral infection efficiency and iNOS gene level, respectively.
      Extracellular and intracellular NO levels were observed by Griess assay kit and
      DAF-FM DA. Mitochondrial transmembrane potential, apoptosis rate and SNO levels
      were determined by flow cytometry, Biotin-Switch method and immunofluoresence
      staining. The expression of iNOS, apoptotic proteins and JNK were assessed by
      immunoblot analysis. RESULTS: The results showed about two times increase in iNOS
      expression and intracellular NO levels response to LPS exposure at 24 hours (P<
      0.05), while not in extracellular NO levels. NO donors, S-nitroso-N
      acetylpenicillamine (SNAP) significantly raised (36.7%, P< 0.05; 38.4%, P< 0.05;
      41.8%, P< 0.05) extracellular NO levels without influencing the intracellular NO
      levels. LPS increased the apoptosis rate (42.4%+/-2.6% vs 2.8%+/-1%, P< 0.05) of
      A549 accompanied by increased Bax levels and decreased Bcl-2 levels through
      activating JNK signaling, which was reversed when we diminished the iNOS
      expression in A549 cells using lentiviral vectors encoding iNOS shRNA in the
      presence of LPS (24.8%+/-3.8% vs 42.4%+/-2.6%, P< 0.05). However, the apoptosis
      rate was increased when SNAP was added (38.8%+/-1.3% vs 24.8%+/-3.8%, P< 0.05).
      Furthermore, we investigated whether ghrelin exert a protective role against LPS
      induced apoptosis and the potential mechanism involved in. Ghrelin alone appeared
      to decrease iNOS expression (32.3%, P< 0.05; 42.3%, P< 0.05), which showed no
      signifiant difference between LPS+ghrelin group and LPS group. However, this
      study showed that ghrelin decreased the intracellular NO production (38.9%, P<
      0.05), protein S-nitrosylation levels (33.5%, P< 0.05), Bax protein expression
      (70.2%, P< 0.05), whereas increasing Bcl-2 protein expression (14.1%, P< 0.05)
      and mitochondrial transmembrane potential (?PsiM) (20.7%, P< 0.05) in the
      presence of LPS. CONCLUSION: The data suggested that NO derived from iNOS induced
      by LPS stimulation exerts an important role in promoting apoptosis of A549 cells,
      and ghrelin abolished intracellular NO production and protein S-nitrosylation
      levels, abrogating the apoptosis of A549 cells partly through inhibiting
      mitochondrial-dependent pathways.

PMID- 30231237
TI  - EYA4 Promotes Cell Proliferation Through Downregulation of p27Kip1 in Glioma.
AB  - BACKGROUND/AIMS: Accumulating evidence suggests that Eyes Absent Homologue 4
      (EYA4) plays an important role in tumorigenesis and progression of various
      cancers. However, the role of EYA4 in glioma development is still unclear.
      METHODS: The expression of EYA4 was examined in glioma tissues by
      immunohistochemistry. Cell viability and apoptosis were analyzed by CCK-8, BrdU
      assay, and flow cytometry. RESULTS: We found that EYA4 was upregulated in glioma,
      and its expression was positively correlated with advanced tumor stage. Moreover,
      higher expression of EYA4 predicted a worse overall survival in patients with
      glioma. Forced overexpression of EYA4 enhanced glioma cell proliferation, and
      EYA4 suppressed the expression of p27Kip1 directly in these cells. Furthermore,
      Six1 was required for EYA4 to suppress the expression of p27Kip1 in glioma.
      CONCLUSION: Together, we demonstrate that EYA4 promotes cell proliferation by
      directly suppressing the expression of p27Kip1 in glioma.

PMID- 30231238
TI  - lncRNA DLG1-AS1 Promotes Cell Proliferation by Competitively Binding with miR-107
      and Up-Regulating ZHX1 Expression in Cervical Cancer.
AB  - BACKGROUND/AIMS: Recent studies have revealed that long non-coding RNAs (lncRNAs)
      are involved in the occurrence and development of various tumors, thereby
      attracting increasing attention from researchers. The important biological
      functions of lncRNAs have been recognized gradually, but their mechanism in
      cervical cancer remains unclear. METHODS: Differentially expressed lncRNAs in
      cervical cancer and para-carcinoma tissues were identified by screening using an
      lncRNA array, and candidate lncRNAs were verified by quantitative real-time PCR.
      A series of bioinformatics and molecular biological methods were adopted to
      investigate the interactions among lncRNAs, microRNAs (miRNAs), and miRNA target
      genes in cervical cancer. Cell viability was measured using a Cell Counting Kit-8
      assay. RESULTS: DLG1-AS1 was the most significantly up-regulated lncRNA in
      cervical cancer tissues, and it was confirmed that cervical cancer patients with
      high DLG1-AS1 expression had a poor prognosis. Down-regulation of DLG1-AS1
      expression suppressed the proliferation of cervical cancer cells. Further
      investigation revealed that DLG1-AS1 eliminated the inhibition of miR-107 on the
      expression of its target gene ZHX1 by competitively binding to miR-107. Moreover,
      rescue assays proved that the effect of DLG1-AS1 on the proliferation of cervical
      cancer cells was dependent on miR-107. CONCLUSION: DLG1-AS1/miR-107/ZHX1 can form
      a competitive endogenous RNA network that regulates the proliferation of cervical
      cancer cells, resulting in tumor progression.

PMID- 30231239
TI  - miR-216b Post-Transcriptionally Downregulates Oncogene KRAS and Inhibits Cell
      Proliferation and Invasion in Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND/AIMS: Increasing evidence has shown that miR-216b plays an important
      role in human cancer progression. However, little is known about the function of
      miR-216b in renal cell carcinoma. METHODS: The expression levels of miR-216b in
      renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The
      biological role of miR-216b in renal cell carcinoma proliferation and/or
      metastasis was examined in vitro and in vivo. The target of miR-216b was
      identified by a dual-luciferase reporter assay. The expression level of KRAS
      protein was measured by western blotting. RESULTS: The expression of miR-216b was
      downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens
      compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the
      3'untranslated region (UTR) of KRAS and inhibit the expression of KRAS through
      translational repression. The in vitro study revealed that miR-216b attenuated
      ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed
      that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor
      function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways.
      CONCLUSION: Our findings provide, for the first time, significant clues regarding
      the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.

PMID- 30231240
TI  - Recovery Time after Hemodialysis Is Inversely Associated with the Ultrafiltration
      Rate.
AB  - INTRODUCTION: The present study aimed to determine the variables that are
      associated with a longer dialysis recovery time (DRT) and to define the
      relationship that exists between DRT and the ultrafiltration rate (UFR) in
      prevalent chronic hemodialysis (CHD) patients. METHODS: We studied 210 prevalent
      CHD of 5 hemodialysis units in Central Italy. Patients were invited to answer to
      the question: "How long does it take you to recover from a dialysis session?"
      Answers to this question were subsequently converted into minutes. Demographic,
      clinical and laboratory parameters were recorded for each patient as well as the
      UFR (mL/kg/h), the dialysate sodium concentration and temperature. RESULTS:
      Median DRT was 180 min (60-420). Ninety five (45%) patients had a DRT >= the
      median value. Mean UFR was 9.2 +/- 3.0 mL/kg/h. Patients with a lower DRT had a
      less prevalent disability in the instrumental activities daily living, had a
      higher UFR, and a lower dialysate temperature, as compared with subjects with
      higher DRT. According to the logistic regression model, UFR was associated with a
      DRT below the median (i.e., 180) in the unadjusted model (OR 1.12; 95% CI 1.02
      1.23; p = 0.019), after adjusting for age and sex (OR 1.11; 95% CI 1.01-1.22; p =
      0.025), and in the fully adjusted model (OR 1.11; 95% CI 1.04-1.22; p = 0.040).
      UFR increase was associated with increasing probability of DRT below the median
      (p for trend = 0.035). The highest tertile of DRT was associated with UFR below
      the mean value (i.e., 9.2 mL/kg/h) in multinomial logistic regression having the
      lowest DRT tertile as reference. DRT was significantly lower in patients with UFR
      > 13 mL/kg/h than in patients with UFR 10-13 or < 10 mL/kg/h. CONCLUSION: DRT is
      inversely associated with UFR in CHD patients. Whether a high UFR should be
      recommended to reduce the DRT needs to be elucidated through an adequate
      prospective randomized study.

PMID- 30231241
TI  - PINK1/Parkin-Mediated Mitophagy Promotes Resistance to Sonodynamic Therapy.
AB  - BACKGROUND/AIMS: Sonodynamic therapy (SDT), based on the synergistic effect of
      low-intensity ultrasound and sonosensitizer, is a potential approach for non
      invasive treatment of cancers. In SDT, mitochondria played a crucial role in cell
      fate determination. However, mitochondrial activities and their response to SDT
      remain elusive. The purpose of this study was to examine the response of
      mitochondria to SDT in tumor cells. METHODS: A human breast adenocarcinoma cell
      line - MCF-7 cells were subjected to 5-aminolevulinic acid (ALA)-SDT, with an
      average ultrasonic intensity of 0.25W/cm2. Mitochondrial dynamics and redox
      balance were examined by confocal immunofluorescence microscopy and western blot.
      The occurrence of mitophagy was determined by confocal immunofluorescence
      microscopy. RESULTS: Our results showed that ALA-SDT could induce mitochondrial
      dysfunction through mitochondrial depolarization and fragmentation and lead to
      mitophagy. The Parkin-dependent signaling pathway was involved and promoted
      resistance to ALA-SDT induced cell death. Finally, excessive production of ROS
      was found to be necessary for the initiation of mitophagy. CONCLUSION: Taken
      together, we conclude that ROS produced by 5-ALA-SDT could initiate PINK1/Parkin
      mediated mitophagy which may exert a protective effect against 5-ALA-SDT-induced
      cell death in MCF-7 cells.

PMID- 30231242
TI  - Oxysophocarpine Retards the Growth and Metastasis of Oral Squamous Cell Carcinoma
      by Targeting the Nrf2/HO-1 Axis.
AB  - BACKGROUND/AIMS: Nuclear factor erythroid 2-related factor 2 (Nrf2) is an
      oncogene in various types of cancers, including oral squamous cell carcinoma
      (OSCC). Oxysophocarpine (OSC) is a natural alkaloid that has multiple
      pharmacological activities. However, the biological functions and molecular
      mechanism underlying the effects of OSC on the growth and metastasis of OSCC are
      unclear. METHODS: Nrf2 levels were determined in OSCC tissues and non-cancerous
      specimens by quantitative real-time PCR, western blotting, and
      immunohistochemistry (IHC) assays. The effects of OSC on OSCC cell growth and
      metastasis were explored (1) using 5-ethynyl-20-deoxyuridine staining and Cell
      Counting Kit-8, colony formation, flow cytometry, wound-healing, Transwell, and
      tube formation assays in vitro; and (2) by establishing a xenograft nude mouse
      model in vivo. The molecular mechanisms underlying the effects of OSC on the
      growth and metastasis of OSCC were investigated in vitro by western blotting,
      caspase-3 activity, and enzyme-linked immunosorbent assays, and in vivo by
      western blotting and IHC assays. RESULTS: The expression levels of Nrf2 in OSCC
      tissues and in cell lines were much higher than in non-cancerous tissues and
      normal oral keratinocytes. The upregulation of Nrf2 was positively correlated
      with a high incidence of lymph node metastasis and advanced histological grade
      and TNM stage, but inversely associated with differentiation and survival of OSCC
      patients. OSC reduced the expression of Nrf2 and heme oxygenase 1 (HO-1) in OSCC
      cells. OSC also inhibited proliferation, migration, invasion, and pro
      angiogenesis of OSCC cells. Moreover, OSC induced cell cycle arrest, enhanced
      apoptosis of OSCC cells in vitro, and decreased OSCC tumor growth in vivo.
      Mechanically, OSC reduced the aggressive behavior of OSCC cells by inactivation
      of the Nrf2/HO-1 signaling pathway. CONCLUSION: Our findings provide evidence
      that OSC inhibits the growth and metastasis of OSCC by targeting the Nrf2/ HO-1
      axis, suggesting that OSC may be a potential therapeutic agent for OSCC.

PMID- 30231243
TI  - FSCN1 Promotes Epithelial-Mesenchymal Transition Through Increasing Snail1 in
      Ovarian Cancer Cells.
AB  - BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT) is one of the key
      mechanisms mediating cancer progression. Snail1 has a pivotal role in the
      regulation of EMT, involving the loss of E-cadherin and concomitant upregulation
      of vimentin, among other biomarkers. We have found FSCN1 promoted EMT in ovarian
      cancer cells, but the precise mechanism of FSCN1 in EMT process has not been
      clearly elucidated. METHODS: The levels of FSCN1 and snail1 were determined in
      epithelial ovarian cancer(EOC) specimen and in ovarian cancer cells by RT-qPCR.
      The changes of EMT makers and effects on snail1 by FSCN1 were examined by
      overexpression or depletion of FSCN1 in EOC cells by RT-qPCR and western
      blotting. The invasiveness of the FSCN1-modified EOC cells was examined in
      transwell assay. Co-immunoprecipitation (IP) was performed to detect the
      interaction between snail1 and FSCN1 in EOC cells. RESULTS: We found FSCN1 and
      snail1 significantly increased in EOC, and especially in EOC with metastasis.
      FSCN1 was positively correlated with snail1 expression at the
      cellular/histological levels. Moreover, we further showed that FSCN1
      physiologically interacted with and increased the levels of snail1 to promote
      ovarian cancer cell EMT. CONCLUSION: FSCN1 promote EMT through snail1 in ovarian
      cancer cells. FSCN1 is an attractive novel target for inhibiting invasion and
      metastasis of EOC cells.

PMID- 30231244
TI  - Analysis of Oral Microbiota Revealed High Abundance of Prevotella Intermedia in
      Gout Patients.
AB  - BACKGROUND/AIMS: Microbes reside in a number of body sites, including the oral
      cavity, and are associated with the progression of many systemic diseases. In
      this study, we aimed to investigate the effects of gout and hyperuricemia (HUA)
      on the composition of oral microbiomes. METHODS: Analysis of the oral microbiota
      from 12 gout patients, 11 HUA patients, and 19 healthy control subjects was
      performed using a deep sequencing approach, and validation of significant changes
      in Prevotella intermedia and Serratia marcescens in new patient cohorts was
      performed using quantitative PCR (qPCR). RESULTS: Our analysis indicated that
      both gout and HUA significantly altered the composition of the oral microbiome in
      patients. Patients with gout or HUA had significantly greater levels of salivary
      Prevotella intermedia but significantly lower levels of Serratia marcescens than
      healthy control subjects. CONCLUSION: We demonstrated the association between the
      oral microbiome and gout and HUA for the first time. In particular, 16S
      sequencing and qPCR analysis revealed significantly higher levels of oral
      Prevotella intermedia in gout/HUA patients, which suggests that these patients
      might be at risk for the development of periodontitis.

PMID- 30231245
TI  - TRPV1 is a Responding Channel for Acupuncture Manipulation in Mice Peripheral and
      Central Nerve System.
AB  - BACKGROUND/AIMS: Acupuncture involves inserting a fine needle into a specific
      point, often called an acupoint, thereby initiating a therapeutic effect
      accompanied by phenomena such as soreness, heaviness, fullness, and numbness.
      Acupoints are characterized as points located in deep tissues with abundant
      sensory nerve terminals, which suggests that there is a strong relationship
      between acupoints and peripheral sensory afferents. In this study, we determined
      whether manual acupuncture (MA) or different frequencies of electroacupuncture
      (EA) share similar mechanisms for activating excitatory neurotransmission.
      METHODS: We performed MA or EA at acupoint ST36 and we also used western blot and
      immunostaining techniques to determine neural changes at the peripheral dorsal
      root ganglion (DRG), spinal cord (SC), and somatosensory cortex (SSC) levels.
      RESULTS: Our results show that either MA or EA at the ST36 acupoint significantly
      increased components of the TRPV1-related signaling pathway, such as pPKA, pPI3K,
      pPKC-pERK, and pAKT (but not pp38 or pJNK) at the peripheral DRG and central SC
      SSC levels. Furthermore, excitatory phosphorylated N-methyl-D-aspartate receptor
      (pNMDA) and pCaMKIIalpha (but not pNR2B, pCaMKIIdelta, or pCaMKIIgamma) also
      increased. These molecules could not increase in the DRG and SC-SSC of TRPV1-/
      mice. CONCLUSION: Our data demonstrates that both MA and EA can activate
      excitatory signals in either peripheral or central levels. We also define that
      TRPV1 is crucial for an acupuncture effect and then initiate excitatory pNR1
      pCaMKII pathway, at peripheral DRG and central SC-SSC level. We suggest that the
      TRPV1 signaling pathway is highly correlated to Acupuncture effect that implies
      the real clinical significance.

PMID- 30231246
TI  - Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor
      Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism.
AB  - BACKGROUND/AIMS: Diabetic nephropathy is the one of the most serious
      microvascular complications of diabetes mellitus, and "metabolic memory" plays a
      vital role in the development of diabetic complications. To investigate the
      effect of epigenetics on metabolic memory, we analyzed the impact of transient
      high-glucose stimulation on the secretion of inflammatory factors from rat
      glomerular mesangial cells. METHODS: Rat glomerular mesangial cells (HBZY-1) were
      divided into three groups: high-glucose group (25 mM glucose), hypertonic group
      (5.5 mM glucose+19.5 mM mannitol), and normal-glucose control group (5.5 mM
      glucose). Mesangial cells were cultured in high-glucose, hypertonic, and normal
      glucose media for 24 h and transitioned to normal-glucose culture for 24, 48, and
      72 h. Then, protein, mRNA, and supernatants were harvested. The expression of
      monomethylated H3K4 was determined by western blot analysis, and the expression
      of the NF-kappaB subunit p65 and histone methyltransferase set7/9 was determined
      by quantitative real-time PCR. The expression of monocyte chemoattractant protein
      1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) was detected by an
      enzyme-linked immunosorbent assay. RESULTS: Compared with the control group,
      H3K4me1 expression was upregulated after transient high-glucose stimulation,
      gradually downregulated in the following 48 h (P < 0.05), and reached the level
      of the control group at 72 h (P > 0.05). The expression of set7/9 was increased
      after 24 h of high-glucose stimulation and the following 24 h and 48 h (P <
      0.05); it then returned to the level of the control group at 72 h. Compared with
      the control group, the increased expression of p65, VCAM-1, and MCP-1 was
      sustained for at least 72 h in the high-glucose group. CONCLUSION: Transient high
      glucose stimulation can induce the persistent secretion of inflammatory factors
      from rat glomerular mesangial cells via histone modification.

PMID- 30231247
TI  - The Plasma LncRNA Acting as Fingerprint in Hilar Cholangiocarcinoma.
AB  - BACKGROUND & AIMS: Current studies have indicated that long non-coding RNAs
      (lncRNAs) could act as tumor biomarkers for disease diagnosis and prognosis
      prediction. In this study, we mainly focused on determining the expression of
      circulating lncRNAs in patients suffering for hilar cholangiocarcinoma (HC),
      aiming to reveal the potential lncRNA as a fingerprint. METHODS: A total 12
      lncRNAs were previously proven to be aberrantly expressed in HC tumor tissues.
      All of the 12 lncRNAs were selected as candidate targets for subsequent
      circulating lncRNA assay. The candidate lncRNAs were validated by qRT-PCR
      arranged in training and validation sets. The risk score analysis was employed.
      Data was presented with receiver operating characteristic curve (ROC). RESULTS:
      Circulating PCAT1, MALAT1, and CPS1-IT1 were significantly increased in plasma
      samples of HC patients in both the training set and validation set. Through ROC
      analysis, we found that the three plasmatic lncRNAs presented the area under ROC
      curve value (AUC) as 0.784, 0.860, and 0.677. Further combination with the three
      factors indicated a higher power (AUC, 0.893; sensitivity, 85.5%; specificity,
      93.2%). CONCLUSION: This was the first time to reveal the potential circulating
      fingerprints for predicting HC. PCAT1, MALAT1, and CPS1-IT1 may act as novel
      early diagnosis biomarkers for predicting HC.

PMID- 30231248
TI  - Sphingosine 1-Phosphate (S1P)/S1P Receptor2/3 Axis Promotes Inflammatory M1
      Polarization of Bone Marrow-Derived Monocyte/Macrophage via G(alpha)i/o/PI3K/JNK
      Pathway.
AB  - BACKGROUND/AIMS: Macrophages, the most plastic cells in the haematopoietic
      system, are found in all tissues and show great functional heterogeneity.
      Sphingosine 1-phosphate (S1P)/ S1P receptors (S1PRs) system is widely involved in
      the process of inflammatory disease, whereas little evidence concerning its role
      in functional macrophage polarization is available. Thus, the present study was
      designed to evaluate the effects of S1P/S1PRs on functional polarization of
      macrophage in mouse bone marrow (BM)-derived monocyte/macrophages (BMMs).
      METHODS: For the detection of M1 macrophage markers, such as CD86, tumor necrosis
      factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1/ chemokine (C-C motif)
      ligand (CCL) 2, nitric oxide synthase (NOS) 2, and macrophage inflammatory
      protein (MIP)-1beta, RT-qPCR and cytometric bead array (CBA) were performed in
      cultured primary BMMs after the treatment with selective S1PR2/3 antagonists or
      specific S1PRs siRNA. Western blotting and immunofluorescence were used for the
      detection of phosphorylation of JNK1/2. RESULTS: BMMs expressed S1PR1-3 and
      interestingly, S1PR2/3, but not S1PR1, mediates S1P-induced M1 macrophage
      polarization of BMMs as their siRNA or antagonists reduced M1 genes' expression.
      We found that PTX (inhibitor of G(alpha)i/o), LY294002 (inhibitor of PI3K) or
      SP600125 (inhibitor of JNK1/2) prevented up-regulation of M1 genes expression
      mediated by S1P/S1PR2/3 signal, and S1P-induced JNK phosphorylation was inhibited
      by antagonists of S1PR2/3, PTX or LY294002. CONCLUSION: Collectively, our results
      demonstrate that S1P/S1PR2/3 plays a key role in regulating M1 type polarization
      of BMMs and acts by activating G(alpha)i/o/PI3K/JNK signaling pathway, with
      potential implications for new approaches to inflammatory liver disease therapy.

PMID- 30231250
TI  - A Survey of Knowledge and Beliefs regarding Autism in Speech-Language
      Pathologists in India.
AB  - BACKGROUND: Speech-language pathologists (SLPs) are significant team members in
      the identification, assessment, and rehabilitation of children with autism. With
      a recent upsurge in the number of children with autism, there arises a need to
      examine SLPs knowledge and skills in identification and intervention of children
      with autism. AIM: The present study is, thus, a novel attempt aimed to
      investigate knowledge and belief of SLPs in the assessment and intervention of
      autism in the Indian context. METHOD: A total of 219 SLPs participated in a web
      based online survey. The study adopted a cross-sectional observational research
      design. RESULTS: The results of the study showed around 43% of the total SLPs
      obtained a good score on the knowledge section and 27% received a positive rating
      for the belief section. Additionally, factors like "educational qualification,"
      "duration of clinical experience," and "caseload of children with autism"
      influenced knowledge and beliefs of SLPs about autism. CONCLUSION: The study
      results indicate that SLPs practicing in India show average and below average
      scores on a questionnaire assessing knowledge and beliefs regarding autism. The
      study findings have implications towards developing improved training and course
      structure related to assessment and intervention of children with autism for SLPs
      practicing in India.

PMID- 30231249
TI  - Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers
      in Human Colon Adenocarcinoma.
AB  - BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) acting as competing endogenous
      RNAs (ceRNAs) play significant roles in the development of tumors, but the
      functions of specific lncRNAs and lncRNA-related ceRNA networks have not been
      fully elucidated for colon adenocarcinoma (COAD). In this study, we aimed to
      clarify the lncRNA-microRNA (miRNA)-mRNA ceRNA network and potential lncRNA
      biomarkers in COAD. METHODS: We extracted data from The Cancer Genome Atlas
      (TCGA) and identified COAD-specific mRNAs, miRNAs, and lncRNAs. The biological
      processes in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes
      (KEGG) were analyzed for COAD-specific mRNAs. We then constructed a ceRNA network
      of COAD-specific mRNAs, miRNAs and lncRNAs and analyzed the correlation between
      expression patterns and clinical features of the lncRNAs involved. After
      identifying potential mRNA targets of 4 lncRNAs related to overall survival (OS),
      we conducted stepwise analysis of these targets through GO and KEGG. Using tissue
      samples from our own patients, we also verified certain analytical results using
      quantitative real-time PCR (qRT-PCR). RESULTS: Data from 521 samples (480 tumor
      tissue and 41 adjacent non-tumor tissue samples) were extracted from TCGA. A
      total of 258 specific lncRNAs, 206 specific miRNAs, and 1467 specific mRNAs were
      identified (absolute log2 [fold change] > 2, false discovery rate < 0.01).
      Analysis of KEGG revealed that specific mRNAs were enriched in cancer-related
      pathways. The ceRNA network was constructed with 64 lncRNAs, 18 miRNAs, and 42
      mRNAs. Among these lncRNAs involved in the network, 3 lncRNAs (LINC00355, HULC,
      and IGF2-AS) were confirmed to be associated with certain clinical features and 4
      lncRNAs (HOTAIR, LINC00355, KCNQ1OT1, and TSSC1-IT1) were found to be negatively
      linked to OS (log-rank p < 0.05). KEGG showed that the potential mRNA targets of
      these 4 lncRNAs may be concentrated in the MAPK pathway. Certain results were
      validated by qRT-PCR. CONCLUSION: This study providing novel insights into the
      lncRNA-miRNA-mRNA ceRNA network and reveals potential lncRNA biomarkers in COAD.

PMID- 30231251
TI  - Diagnostic Difficulties in Primary Pauci-Melanotic Leptomeningeal Melanomatosis.
AB  - We present a rare case of primary malignant melanoma of the central nervous
      system. We underline the difficulties we faced during diagnostic procedures.
      Finally, postmortem examination revealed the diagnosis of primary pauci-
      melanotic leptomeningeal melanomatosis.

PMID- 30231252
TI  - Non-Antibiotic Herbal Therapy (BNO 1045) versus Antibiotic Therapy (Fosfomycin
      Trometamol) for the Treatment of Acute Lower Uncomplicated Urinary Tract
      Infections in Women: A Double-Blind, Parallel-Group, Randomized, Multicentre, Non
      Inferiority Phase III Trial.
AB  - INTRODUCTION: This randomized, controlled, Phase III non-inferiority clinical
      trial aimed to determine whether herbal therapy with Canephron(r) N (BNO 1045) is
      non-inferior to fosfomycin trometamol (FT) in treating acute lower uncomplicated
      urinary tract infections (uUTIs). MATERIALS AND METHODS: Women aged 18-70 years
      with typical symptoms of newly diagnosed acute lower uUTIs were randomized to BNO
      1045 (n = 325) or FT (n = 334), with corresponding matched placebo. The primary
      endpoint was the proportion of patients who received additional antibiotics (ABs)
      to treat uUTIs between Days 1 and 38 +/-3. RESULTS: Between Days 1 and 38, 238
      (83.5%) patients in the BNO 1045 group and 272 (89.8%) patients in the FT group
      received no additional ABs. At a 15% non-inferiority margin, BNO 1045 was non
      inferior to FT in treating uUTIs (non-AB rate difference: -6.26%; 95% CI -11.99
      to -0.53%; 2-sided p = 0.0014). Adverse event rates were similar between groups,
      with higher rates of gastrointestinal disorders in the FT group and
      pyelonephritis in the BNO 1045 group. During the trial, no patient died or
      discontinued due to a treatment-related adverse event. CONCLUSIONS: BNO 1045 has
      the potential to reduce outpatient use of ABs for uUTIs and thus may have a
      significant impact on antimicrobial stewardship strategies. TRIAL REGISTRATION:
      NCT02639520, EudraCT number 2013-004529-99.

PMID- 30231253
TI  - The Pubic Diastasis Measurement, a Key Element for the Diagnosis, Management, and
      Prognosis of the Bladder Exstrophy.
AB  - OBJECTIVE: To demonstrate the feasibility of measuring the fetal pubic diastasis
      (PD) distance on antenatal ultrasound in normal fetuses and to compare it to
      fetuses with bladder exstrophy. METHODS: Firstly, a prospective multicentric
      study was conducted to determine the feasibility of the PD ultrasound measurement
      during the second half of pregnancy. Secondly, data from a single center were
      used to develop a nomogram for PD values in normal fetuses. Thirdly,
      retrospective PD measurements were collected from fetuses with bladder exstrophy,
      diagnosed in seven French Multidisciplinary Centers for Prenatal Diagnosis
      (MCPDs). RESULTS: Operators from several MCPDs examined 868 fetuses and found
      that overall PD ultrasound measurement was feasible in 71% of cases and that the
      ossification of pubic points increased to be always visible from 27 weeks of
      gestation onward. Performed in a single center by a referring operator on 1,539
      fetuses, the feasibility reached 94.74%. Both set of measurements were concordant
      (mean PD distance value of 5.42 +/- 1.8 mm). Interestingly, all 23 fetuses with
      bladder exstrophy showed a significantly larger PD distance (mean 15.74 +/- 3.9
      mm). CONCLUSION: PD measurement in the fetus is feasible and reliable in the
      second half of gestation and can be used to support the antenatal diagnosis of
      bladder exstrophy with PD values exceeding 10 mm.

PMID- 30231254
TI  - Histological and Mechanical Assessment of Decellularized Porcine Biografts, and
      Its Biological Evaluation following Aortic Implantation during Mid-Term Follow
      Up.
AB  - AIMS: Prosthetic graft infection frequently requires graft replacement. Among
      other options, a biological graft could serve as an alternative choice.
      Decellularization reduces tissue immunogenicity. Our aim was to determine an
      efficient decellularization method and to evaluate the decellularized porcine
      biografts' adaptability. METHODS: Four different protocols were implemented to
      decellularize porcine aortic segments (n = 4). Cell removal effectiveness and
      matrix structure preservation were histologically examined. Mechanical tests were
      performed. Decellularized porcine grafts were interpositioned in a porcine aorta.
      After a 6-month period, implanted samples were removed and evaluated using light
      and electron microscopy. RESULTS: Histological results showed complete removal of
      cells and preserved connective tissue fiber structure following
      decellularization, using sodium dodecyl sulfate and sodium azide. Pressure tests
      demonstrated similar compliance to fresh vessels. In 9 out of 10 cases, pigs
      survived the follow-up period. Graft rejection, intimal hyperplasia, reocclusion
      and/or aneurysm formation were not observed. Presence of host cells and
      neoendothelialization were microscopically confirmed. CONCLUSIONS: This
      decellularization protocol enables a cost-effective preparation of biological
      grafts featuring reduced immunogenicity. The implanted grafts did not degenerate
      during the 6-month follow-up period, the lack of graft rejection suggests
      acceptable immunological tolerance, while recipient cells migrate into,
      proliferate and differentiate, thus creating the possibility for further use as
      an optional vascular graft.

PMID- 30231255
TI  - Using the Kinetic Estimating Glomerular Filtration Rate Equation for Estimating
      Glomerular Filtration Rate and Detecting Acute Kidney Injury: A Pilot Study.
AB  - BACKGROUND: Estimating the glomerular filtration rate (eGFR) when the creatinine
      (Cr) is rapidly changing, as in acute kidney injury (AKI), has been a challenge.
      The Kinetic Estimated Glomerular Filtration Rate (KeGFR) formula by S. Chen
      estimates the GFR in the acute state by factoring the time interval between
      rising Cr values and the volume of distribution (VD). It provides the clinician
      with an eGFR value for each non-steady state Cr value. We applied the KeGFR
      formula to detect AKI in an adult non-ICU inpatient setting. We then compared
      KeGFR with the current standard Acute Kidney Injury Network (AKIN criteria) and
      Risk Injury Failure Loss End-Stage Kidney Disease (RIFLE criteria) and new
      criteria (Waikar-Bonventre, Delta check) for AKI detection. METHODS: A total of
      250 consecutive adult patients admitted to the Medical wards were screened.
      Patient episodes with a change in Cr of > 4.3% (Biological Variation) were
      included in the study (n = 80). The KeGFR equation was applied to this cohort
      after calculating the VD individually after estimating the initial GFR by using
      MDRD equation. A fall in KeGFR of 25% or more was considered as AKI. The AKIN,
      Waikar-Bonventre, RIFLE, and Delta Check criteria were also applied to this
      cohort and compared with the KeGFR criterion. Clinical adjudication was performed
      when there was discordance between AKI episodes detected by AKIN and KeGFR
      criteria. RESULTS: There were 50 episodes of AKI by AKIN classification and 31
      episodes by KeGFR criterion. All but 1 (30) episode detected by KeGFR criterion
      fulfilled the AKI definition by AKIN. AKIN diagnosed an additional 20 episodes.
      However, all of these had an elevated Cr level on admission; thus, requiring the
      incorporation of baseline Cr by AKIN which is not part of the KeGFR formula. Five
      of these 20 patients were deemed as not having AKI by clinical adjudication. All
      patients with in-hospital AKI and ongoing AKI were detected by both the criteria.
      The KeGFR criteria detected almost all (24/25) episodes of AKI identified by the
      Waikar-Bonventre method. The latter method detected 77% (24/31) of the AKI
      episodes identified by KeGFR. CONCLUSION: The KeGFR equation can be readily
      applied to estimate GFR in the non-steady state. A KeGFR-based criterion
      successfully detected ongoing and in-hospital AKI in this study. Community
      acquired AKI that did not progress after admission was not detected by the KeGFR
      criterion.

PMID- 30231256
TI  - A Kinematic Analysis of Coarticulation Effects on Schwa.
AB  - PURPOSE: This study investigated coarticulatory effects on schwa. The purpose was
      to establish a viable phonetic environment and analysis for future studies of
      coarticulation, particularly in motor speech disorders. METHOD: Seven female
      adults read 2 phrases containing 4 target words in a CVC structure embedded in
      the carrier phrases, "Put a CVC here" and "Get CVC a puppy." A 3D electromagnetic
      articulography system was used to track lingual movements during schwa
      production. Two indices of coarticulation were employed: (a) tongue position
      difference between the temporal midpoint (grand mean of each speaker) and the
      onset/offset of schwa immediately following or preceding a transconsonantal vowel
      and (b) tongue position differences between the grand mean of each speaker and
      each utterance repetition, both measured at the temporal midpoint of the schwa.
      RESULTS: Both measures indicated that schwa is significantly influenced by
      transconsonantal corner vowels. The magnitude of coarticulation effects on schwa
      varied among the 4 corner vowels in the order of /i/>/alpha/ = /ae/>/u/.
      CONCLUSION: Findings support the use of schwa in future studies when examining
      coarticulatory effects in people with and without motor speech disorders. Some
      methodological issues such as selection of measurement points and speech stimuli
      are also discussed.

PMID- 30231257
TI  - Mind the Gap: Genetic Variation and Personalized Therapies for Cardiomyopathies.
AB  - Inherited cardiomyopathies are cardiovascular disorders that are one of the
      leading causes of death and are strongly associated with genetic mutations. These
      include hypertrophic, dilated, restrictive, as well as arrhythmogenic right
      ventricular cardiomyopathies. Among the patients presenting with these specific
      forms of cardiomyopathies, there is significant phenotypic, genotypic, and
      environmental heterogeneity. Over the years, the identification of the underlying
      mutations common to specific forms of cardiomyopathies have facilitated clinic
      diagnosis. However, the variation between patient genetics and phenotypes
      highlights the need for improved understanding of these diseases and the
      development of innovative treatments. To better understand the diseases,
      researchers are capitalizing on two innovative technologies: cardiac
      reprogramming and gene editing using CRISPR-Cas9. Deriving cardiomyocytes from
      patient blood samples and gene editing allows for the efficient generation of
      cellular and animal models that allow researchers to model the disease more
      accurately. In addition, the recent advances in high throughput drug screening
      allows for the efficient testing of patient-derived cardiomyocytes for patient
      specific susceptibility to various drugs that are currently approved. In
      addition, this technology can facilitate the development of new pharmacological
      compounds for the treatment of specific cardiomyopathies. Overall, the recent
      technological advances in molecular medicine now presents an opportunity to gain
      unprecedented insight into solving the complex issue of inherited
      cardiomyopathies. These techniques pave the way for the new generation of
      personalized medicine in treating cardiovascular diseases.

PMID- 30231258
TI  - Elevated G-Protein Receptor 125 (GPR125) Expression Predicts Good Outcomes in
      Colorectal Cancer and Inhibits Wnt/beta-Catenin Signaling Pathway.
AB  - BACKGROUND G-protein receptor 125 (GPR125), as a transmembrane signal transducer,
      is involved in regulating cancer development. Although GPR125 is related with
      several cancers, its role in colorectal cancer (CRC) and the underlying mechanism
      are still unknown. Here, we investigated the clinical significance of GPR125 in
      CRC. MATERIAL AND METHODS We assessed the expression level of GPR125 in CRC
      tissues by analyzing 3 datasets in the Gene Expression Omnibus (GEO) database and
      in human samples. The correlation between GPR125 expression and
      clinicopathological features was further analyzed. Survival analysis was
      performed to assess the association between GPR125 expression and recurrence-free
      survival (RFS). Cox logistic regression analysis was used to analyze the role of
      GPR125 expression in overall survival (OS). Moreover, we activated the Wnt
      pathway in HCT116 cells to investigate their potential mechanism. RESULTS
      Analysis of the GEO database showed that the expression of GPR125 was down
      regulated in CRC tissues, consistent with our human samples experiments, and
      patients with higher GPR125 expression had a longer RFS. Also, we found that high
      GPR125 expression was associated with better tumor outcomes in clinical stage,
      metastasis, and KRAS status. Cox logistic regression analysis demonstrated that
      GPR125 was an independent prognostic factor for favorable outcome.
      Mechanistically, GPR125 overexpression inhibited the beta-catenin transcriptional
      activity, and down-regulated the expression levels of the Wnt downstream proteins
      Axin2, c-Myc, cylinD1, and lef-1. CONCLUSIONS GPR125 may be a potential prognosis
      related anti-oncogene and its effects on inactivating Wnt/beta-catenin signaling
      pathway might be a key link to inhibiting CRC formation.

PMID- 30231260
TI  - Peroral endoscopic myotomy and peroral endoscopic pyloromyotomy as a single
      procedure for concomitant achalasia and gastroparesis.

PMID- 30231259
TI  - Integrated Electronic Discharge Summaries-Experience of a Tertiary Pediatric
      Institution.
AB  - OBJECTIVE:  Succinct and timely discharge summaries (DSs) facilitate ongoing care
      for patients discharged from acute care settings. Many institutions have
      introduced electronic DS (eDS) templates to improve quality and timeliness of
      clinical correspondence. However, significant intrahospital and intraunit
      variability and application exists. A review of the literature and guidelines
      revealed 13 key elements that should be included in a best practice DS. This was
      compared against our pediatric institution's eDS template-housed within an
      integrated electronic medical record (EMR) and used across most inpatient
      hospital units. METHODS:  Uptake and adherence to the suggested key elements was
      measured by comparing all DSs for long stay inpatients (> 21-day admission)
      during the first year of the EMR eDS template's usage (May 2016-April 2017).
      RESULTS:  A total of 472 DSs were evaluated. Six of 13 key elements were
      completed in > 98.0% of DSs. Conversely, only < 5.0% included allergies or
      adverse reaction data, and < 11.0% included ceased medications or pending
      laboratory results. Inclusion of procedure information and pending laboratory
      results significantly improved with time (p = 0.05 and p < 0.04, respectively),
      likely as doctors became more familiar with EMR and autopopulation functions.
      Inclusion of "discharge diagnosis" differed significantly between medical (n =
      406/472; 99.0%) and surgical (n = 32/472; 51.6%) DSs. CONCLUSION:  Uptake and
      adherence to an EMR eDS template designed to meet best practice guidelines in a
      pediatric institution was strong, although significant improvements in specific
      data elements are needed. Strategies can include a modification of existing eDS
      templates and junior medical staff education around best practice.

PMID- 30231261
TI  - Recanalization of postoperative biliary disconnection with intraductal
      cholangioscopy-assisted forceps retrieval of rendezvous guidewire.

PMID- 30231262
TI  - Visual Distraction During Sleep Induction with Propofol in Pediatric Patients -
      Can Cartoon Watching Influence the Sedative Dose?
AB  - BACKGROUND: In general anesthesia, cartoon watching and playing video games
      reduce anxiety in children. It is unknown whether watching a video in the
      intervention room has a similar effect, and therefore is able to reduce sedative
      doses in children undergoing small medical procedures. Aim of this prospective
      study was to determine the effect of watching a standardized cartoon immediately
      before and during sleep induction for deep sedation on consumption of propofol in
      children. PATIENTS AND METHODS: 50 children aged 2-14 years undergoing deep
      sedation were randomly assigned to 2 groups: (A) watching or (B) not watching a
      standardized videoclip during sleep induction with propofol. The achievement of
      predefined sedation depth was objectified by measuring Comfort Score (aim 10-14)
      and Bispectral Index (aim 50-60). RESULTS: The median sleep induction dose of
      propofol did not differ in both groups (A: 1.76 (0.62-4.37) mg/kg; B: 1.37 (0.66
      5.26) mg/kgKG; p=0.65). Cartoon watching was associated with shorter sleep onset
      latency (A: 120 (60-480)s; B: 240 (40-600)s; p=0.043). Subgroup analysis reveals
      this especially for school children and girls. In both groups no complications
      occurred. CONCLUSION: Children watching a standard cartoon during sleep induction
      for deep sedation have a shorter sleep onset time but sedative dose is not
      reduced.

PMID- 30231263
TI  - New Cytotoxic Cycloartane Triterpenes from the Aerial Parts of Actaea
      heracleifolia (syn. Cimicifuga heracleifolia).
AB  - One new 15,16-seco-cycloartane triterpene (1: ), three new cycloartane triterpene
      glycosides (2: -4: ), and five known compounds (5: -9: ) were isolated from the
      aerial parts of Actaea heracleifolia. The chemical structures of these compounds
      were determined on the basis of NMR analysis, HRTOF-ESIMS data, and other
      spectroscopic methods. Selected compounds were evaluated for their cytotoxicity
      against human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) in
      vitro. Compounds 3: and 4: showed weak activity against the HL-60, A-549, and MCF
      7 cell lines with IC50 values ranging from 21.34 to 36.98 uM.

PMID- 30231264
TI  - Endobronchial Ultrasound for Benign Tracheal Stenosis.
AB  - We reported the role of endobronchial ultrasound as complement to standard
      diagnostic exams to better define the benign tracheal stenosis (i.e., thickness
      and tracheal cartilage integrity) and to plan the treatment with flexible instead
      of rigid bronchoscope. Under sedation and spontaneous ventilation, the flexible
      bronchoscope was inserted through the laryngeal mask airway that assured the
      ventilation. The stenosis was first resected with cold scissors and then dilated
      with balloon catheter. This strategy was successfully applied in five consecutive
      patients. Inclusion criteria for the procedure were stenosis < 1 cm in length,
      without tracheomalacia and with integrity of airway cartilage.

PMID- 30231265
TI  - Introducing the New Fifth Issue of Seminars.

PMID- 30231266
TI  - Exploring the Effectiveness of an Intensive Treatment Program for School-Age
      Children Who Stutter, Camp Dream. Speak. Live.: A Follow-up Study.
AB  - The purpose of this follow-up study was to explore the effectiveness of an
      intensive treatment program-Camp Dream. Speak. Live.-within older, school-age
      children who stutter. Twenty-three school-age children who stutter (age range: 7
      14 years) attended this week-long intensive therapy program for the first time.
      Outcome measures included Overall Assessment of the Speaker's Experience of
      Stuttering and the Patient Reported Outcomes Measurement Information System
      Pediatric Peer Relationships Form. Findings demonstrate significant improvements
      in quality of life and communication attitudes can be achieved in a short period
      of time when increasing fluency is not a target.

PMID- 30231267
TI  - Friendship Quality, Friendship Quantity, and Social Participation in Adults with
      Traumatic Brain Injury.
AB  - Adults with traumatic brain injury (TBI) often report reduced social
      participation and loss of friends, but little is known about quality of
      friendship after TBI. Our objective was to characterize social participation,
      friendship quantity, and friendship quality of adults with TBI and a comparison
      group of uninjured adults. Participants included 18 adults with moderate to
      severe TBI and 16 of their informant friends; and 18 uninjured adults and 11 of
      their informant friends. The main measures used were the Participation Assessment
      with Recombined Tools-Objective, the Social Network Questionnaire, and the McGill
      Friendship Questionnaire. Participants with TBI reported significantly less
      social participation and had fewer total friends, although this difference was
      not statistically significant. Adults with TBI differed from their friends on one
      measure of friendship quality, but reports for friendship quality were high in
      both groups. Adults with TBI reported overall high levels of friendship quality
      despite having lower levels of social participation compared with uninjured
      adults. Future research should investigate how the balance of quantity and
      quality of friendships relates to satisfaction with social participation and
      overall quality of life.

PMID- 30231268
TI  - Caregivers' Perceptions of Their Child's Language Disorder: Alignment between
      Caregivers and Speech-Language Pathologists.
AB  - Caregivers' perceptions regarding their child's language disorder may influence
      caregivers' involvement in therapy as well as daily home interactions, thus
      impacting developmental outcomes. However, little is known about the alignment
      between caregivers' perceptions of their child's language disorder and those of
      speech-language pathologists (SLPs), nor of factors that might relate to
      alignment between caregivers and SLPs. This study addressed three aims: (1) to
      characterize caregivers' perceptions regarding children's quality of
      communicative interactions, competence in communicative abilities, and outcomes
      of communicative improvement; (2) to measure alignment between caregivers' and
      SLPs' perceptions; and (3) to explore caregiver- and child-level factors that
      might relate to alignment. Caregivers and SLPs of 3- to 4-year-old children
      currently receiving treatment for language disorders completed questionnaires to
      assess perceptions along with two caregiver factors (maternal education and self
      efficacy) and child language disorder severity. Caregivers' perceptions were more
      positive and more variable than those of SLPs. However, caregivers and SLPs
      agreed in rating perceptions of present and future outcomes higher than either
      quality or competence. Maternal education, caregiver's self-efficacy, and
      children's language disorder severity were not related to alignment between
      caregivers and SLPs. Given the variability in caregivers' perceptions, future
      research should explore the role of perceptions in children's language
      intervention outcomes.

PMID- 30231269
TI  - Radiation-Induced Skin Changes after Postmastectomy Radiation Therapy: A Pilot
      Study on Indicators for Timing of Delayed Breast Reconstruction.
AB  - BACKGROUND:  Delayed autologous breast reconstruction is commonly recommended in
      patients requiring postmastectomy radiation. This study examines gross and
      histologic changes in the breast skin of patients who have undergone
      postmastectomy radiation to help determine when radiation-induced skin changes
      begin to stabilize. METHODS:  A prospective pilot study was conducted on eight
      patients with invasive breast cancer who required mastectomy and radiotherapy. At
      the time of mastectomy and 2, 4, 6, 8, and 12 months after completion of
      radiotherapy, a punch biopsy was taken from the radiated mastectomy skin of each
      patient. Serial standardized photographs were taken before and after radiotherapy
      to evaluate the degree of hyperpigmentation and graded by three blinded plastic
      surgeons. Skin biopsies were processed for histologic assessment of inflammation,
      elastin organization, and vascularity. RESULTS:  Grading of patient photographs
      revealed an increase in hyperpigmentation after radiotherapy compared with
      baseline with a gradual improvement over time. SMAD3 immunostaining demonstrated
      a trend toward an increase in inflammation over 12 months. The elastin
      distribution within samples showed an increase in fiber disorganization,
      thickening, and clumping, with no improvement throughout the study period. The
      average number of vessels per high powered field decreased steadily through the
      duration of the study. CONCLUSIONS:  Histologic changes in dermal inflammation,
      elastin organization, and vascularity do not appear to correspond with the
      gradual improvement of hyperpigmentation, resulting from postmastectomy
      radiation. These histologic changes persist beyond the 12 month observation
      period and will require clinical correlation to determine the potential impact on
      postoperative outcomes.

PMID- 30231270
TI  - Effects of Systemic and Local Caffeine on Vessel Diameter, Anastomosis Patency,
      and Intimal Hyperplasia in the Rat.
AB  - BACKGROUND:  The use of caffeine is not recommended prior to elective
      microsurgery due to its demonstrated negative effects on vessel anastomosis by
      the presumed sympathomimetic induction of vasoconstriction. In this study, we
      aimed to elucidate the systemic and local effects of caffeine on vessel diameter,
      anastomosis patency, and degree of intimal hyperplasia during the healing
      process. METHODS:  Twenty-five rats were randomly assigned to five groups: (1)
      negative control, (2) preoperative systemic caffeine, (3) postoperative systemic
      caffeine, (4) perioperative systemic caffeine, and (5) a local caffeine group.
      Both the right and left femoral arteries were used. Ten anastomoses were
      performed per group. The arterial diameter was measured by micrometer,
      anastomosis patency was assessed surgically and histologically, and the
      histological examination was conducted 3 weeks postoperatively to determine
      intimal hyperplasia. RESULTS:  The overall patency rate was 96%. Mild
      vasoconstriction was observed in the systemic caffeine groups (statistically
      insignificant); however, there were no negative effects on anastomosis patency.
      Local caffeine irrigation resulted in significant vasodilatation in the local
      caffeine group (p = 0.001); a similar effect was not observed in the other
      groups. There was a significant decrease in the intima/media ratio in the local
      caffeine group (p < 0.01), when compared with the control and systemic caffeine
      groups. No other intima/media ratio differences were observed among other
      comparison groups. CONCLUSION:  The systemic administration of caffeine, although
      statistically insignificant, has an observable effect on vasoconstriction.
      However, it does not appear to have negative effects on anastomosis patency
      regardless of its application period (pre-, post-, or perioperatively). The local
      application of caffeine resulted in considerable vasodilatation as opposed to the
      vasoconstriction effect in the systemic caffeine groups. Decreased intimal
      hyperplasia at the anastomosis edge, and antifibrotic properties in the surgical
      field were also observed in this group. Histologically, the local caffeine group
      demonstrated an additional beneficial effect on anastomosis remodeling.

PMID- 30231272
TI  - Prenatal Prediction of Difficult Intubation in Periviable Neonates Using Standard
      Fetal Biometric Parameters.
AB  - OBJECTIVE:  To assess whether standard fetal biometric parameters can be used to
      predict difficult intubations in periviable neonates undergoing resuscitation.
      STUDY DESIGN:  This is a retrospective case-control study of periviable neonates
      delivered at 23 to 256/7 weeks at an academic hospital during a 5-year period in
      whom intubation was attempted. Standard fetal biometric measurements were
      included if they were taken within 7 days of delivery. Primary outcome was
      intubation in one attempt and was compared with more than one attempt. Data were
      also collected for fetal gestational age at delivery, neonatal birth weight,
      estimated fetal weight, head circumference, biparietal diameter, and abdominal
      circumference. Parametric and nonparametric statistical tests used p < 0.05 as
      significant. RESULTS:  In total, 93 neonates met the inclusion criteria. The mean
      estimated fetal weight was 675 g (standard deviation [SD] +/- 140), and the mean
      neonatal birth weight was 706 g (SD +/- 151). The median interval between fetal
      ultrasound and delivery was 3 days (range: 0-7 days). A total of 45 neonates
      (48.3%) required more than one intubation attempt. The median number of
      intubation attempts was 1 (range: 1-10). There was no association between
      intubation difficulty and fetal abdominal circumference, biparietal diameter,
      head circumference, gestational age, estimated fetal weight, and neonatal birth
      weight (all p > 0.05). CONCLUSION:  Standard biometry in periviable neonates does
      not predict intubation difficulty.

PMID- 30231271
TI  - Management of Microsurgical Patients using Intraoperative Unfractionated Heparin
      and Thromboelastography.
AB  - BACKGROUND:  Maintaining optimal coagulation is vital for successful
      microvascular tissue transfer. The viscoelastic thromboelastography (TEG) is a
      modern and dynamic method to assess a patient's coagulation status. The aim of
      this study was to evaluate its diagnostic capabilities of identifying
      microvascular complications. METHODS:  A retrospective chart review was conducted
      for the most recent 100 cases of abdominal free flap breast reconstruction of a
      single surgeon. Patient demographics, medical history, clinical, and operative
      details were documented. Thrombocyte counts, prothrombin time (PT), activated
      partial thromboplastin time (aPTT), and various TEG parameters were gathered for
      preoperative, intraoperative, and two postoperative time points. RESULTS:  A
      total of hundred patients were identified, who underwent 172 abdominal-based free
      flaps for breast reconstruction. TEG was more dynamic compared with PT or aPTT
      and demonstrated borderline hypocoagulate values intraoperatively upon
      unfractionated heparin administration and hypercoagulate values postoperatively.
      In contrast, PT and aPTT demonstrated a continuously hypocoagulable state.
      Complications included five thrombotic events and three hematomas. The thrombotic
      cases had much steeper increases of TEG-G between surgery and postoperative day 2
      (p = 0.049), while PT and aPTT failed to identify these patients. Of those, two
      resulted in flap loss (1.2%) that both occurred in patients with abdominal scars
      from previous surgery. CONCLUSION:  The TEG is a useful adjunct for monitoring
      coagulation status in microsurgical breast reconstruction. When thrombosis at the
      anastomosis occurs, TEG correlates with a more rapid rebound from an
      intraoperative hypocoagulable state to a postoperative hypercoagulable state,
      when using the TEG. The TEG is a valuable tool for a more dynamic assessment of
      the patients' changing coagulation status.

PMID- 30231273
TI  - Gestational Weight Gain during Pregnancy as an Important Factor Influencing a
      Successful Trial of Labor following Two Previous Cesareans.
AB  - OBJECTIVE:  We sought to identify factors associated with a successful trial of
      labor (TOL) following two cesarean deliveries (CDs) in a contemporary North
      American cohort. STUDY DESIGN:  This is a retrospective cohort study of term,
      nonanomalous, singleton, vertex pregnancies attempting a vaginal birth after
      cesarean (VBAC) following a history of two previous CDs in the United States from
      2012 to 2014. Maternal and intrapartum factors were analyzed using chi-square
      tests and multivariable logistic regression. RESULTS:  A total of 22,762 women
      met the inclusion criteria and underwent TOL. Of these, 12,192 (53.6%) had a
      VBAC. Using multivariate logistic regression, previous vaginal delivery and
      delivery at 40 to 41 weeks' gestation were associated with VBAC; maternal age,
      education, Medicaid insurance, non-Caucasian race/ethnicity, weight (overweight
      or obese), and gestational weight gain above the Institute of Medicine guidelines
      (adjusted odds ratio: 0.88; 95% confidence interval: 0.81-0.95) were associated
      with CD. Induction of labor did not affect the VBAC rate. CONCLUSION:  For those
      desiring a TOL after two previous CDs, prospective studies are needed to assess
      interventions that limit gestational weight gain as well as the safety and
      optimal timing of an induction of labor. The decision to attempt a TOL should be
      guided by counseling regarding the risks, benefits, and chances of a successful
      TOL.

PMID- 30231274
TI  - Opioid Detoxification in Pregnancy: Systematic Review and Meta-Analysis of
      Perinatal Outcomes.
AB  - OBJECTIVE:  We sought to compare the efficacy and safety of detoxification from
      opioids compared with opioid replacement therapy (ORT) during pregnancy. STUDY
      DESIGN:  We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov
      from inception to June 2017 for English-language randomized-controlled trials or
      cohort studies that compared detoxification with ORT. We sought studies with
      outcomes data on maternal abstinence at the time of delivery, neonatal abstinence
      syndrome (NAS), stillbirth, and preterm birth (PTB). We calculated pooled
      relative risks (RRs) with a random-effects model, assessed heterogeneity using
      the chi-square test for heterogeneity, and quantified heterogeneity using the I2
      test. We assessed publication bias using funnel plots and the Harbord test.
      RESULTS:  Three cohort studies met the inclusion criteria; eligible studies
      included 235 women with opioid use disorder in pregnancy. Maternal detoxification
      was associated with increased risk of relapse (RR = 1.91; 95% confidence interval
      [CI] = 1.14-3.21); however, no treatment differences were observed for the rates
      of NAS (RR = 0.99; 95% CI = 0.38-2.53) or PTB (RR = 0.39; 95% CI = 0.10-1.60).
      CONCLUSION:  Our findings suggest an increased risk of relapse with
      detoxification treatment compared with ORT; however, detoxification does not
      alter the risk of PTB or NAS. Further studies should confirm our findings and
      explore mechanisms to fight the current opioid epidemic.

PMID- 30231275
TI  - Risk Assessment and Treatment Guide for Obstetric Thromboprophylaxis:
      Comprehensive Review of Current Guidelines.
AB  - OBJECTIVE:  Currently, there are numerous recommendations and often conflicting
      guidance provided for venous thromboembolism (VTE) prophylaxis in pregnancy. Our
      objective was to create a one-page risk assessment and treatment guide based on a
      review of the most recent and evidence-based publications on this subject to
      simplify the approach and allow all obstetric patients to be properly assessed
      for risk of VTE and treated if indicated. STUDY DESIGN:  We identified studies by
      completing a Pubmed and MEDLINE search from January of 1980 through March 2017
      with articles utilizing a specific combination of the selected general keywords
      (thrombophilia, pregnancy, VTE, prophylaxis, hypercoagulability, antepartum,
      postpartum, risk, etc.). We completed the search at the saturation point, meaning
      that all combinations of the relevant words were directing us to the same
      articles. After collecting the relevant sources and reviewing them, a total of 10
      articles/guidelines were selected for inclusion in the analysis. RESULTS:  We
      outlined every recommendation in the identified articles and guidelines and
      included any recommendation that was cited in at least three different sources in
      the final guide. We used American College of Obstetrics and Gynecology
      recommendations as the base for screening and dosing guidelines and utilized
      known and published absolute risk values and odds ratios to stratify risk
      factors. This stratification was used for both antepartum and postpartum
      recommendations and a single-page guideline was created. CONCLUSION:  This
      compilation of guidelines integrates the complicated topic into a simple
      comprehensive guide where women can be identified early and accurately for
      appropriate VTE prophylaxis to protect them during and after pregnancy.

PMID- 30231276
TI  - MR Pelvimetry for Breech Presentation at Term- Interobserver Reliability,
      Incidental Findings and Reference Values.
AB  - PURPOSE:  Antepartal MR pelvimetry is used to assess the viability of vaginal
      breech delivery. We evaluated the reliability of MR pelvimetric measurements as
      well as incidental findings noted by different clinicians and assessed potential
      reference values. METHODS:  In this monocentric study, the radiologic database
      was searched for obstetric MR pelvimetries with singleton breech pregnancies
      between 1999 and 2016. 99 consecutive MR pelvimetries were included. A
      structured, independent review was performed by six observers with three clinical
      experience levels (attending, fellow, junior resident from the departments of
      radiology and obstetrics). Image analysis entailed the quantitative assessment of
      conjugata vera (CV) and diameter transversalis (DT), image quality and incidental
      findings. Obstetric data was retrieved from the obstetric database for reference
      value assessment. RESULTS:  Interobserver agreement was strong throughout (mean
      intraclass correlation coefficient range: 0.889 - 0.968). The individual
      measuring biases ranged between 0 - 2 mm, and the average limits of agreement
      were +/- 3 mm. Regarding the mode of delivery, the recommended cesarean section
      (rCS) group showed significantly smaller CV measurements (CV: 11.37 +/- 0.73, p
      value < 0.0001) than any other delivery group. No statistical difference in CV
      between the vaginal delivery and unplanned cesarean section groups was found (p
      value 0.902). DT measurements only showed a significant difference between rCS
      and elective cesarean section (p-value 0.039). 134 incidental findings were
      noted. CONCLUSION:  Strong interobserver agreement irrespective of the reader's
      experience level supports MR pelvimetry as a reliable method for identifying
      women with fetopelvic disproportion in breech presentation. For a comprehensive
      appraisal of incidental findings, radiologic expertise is vital. KEY POINTS:   .
      MR pelvimetry is a reliable method irrespective of the reader's experience
      level.. . Conjugata vera measurements aid in the prepartal viability assessment
      of vaginal breech delivery.. . Incidental findings are relatively common..
      CITATION FORMAT: . von Bismarck A, Ertl-Wagner B, Stocklein S et al. MR
      Pelvimetry for Breech Presentation at Term- Interobserver Reliability, Incidental
      Findings and Reference Values. Fortschr Rontgenstr 2018; DOI: 10.1055/a-0715
      2122.

PMID- 30231277
TI  - ?

PMID- 30231278
TI  - [Dementia Diagnosis in General Practitioner Care - Attitudes, Procedures and
      Challenges from the Perspective of General Practitioners in Rhineland
      Palatinate].
AB  - BACKGROUND: It is regularly criticized that the detection of dementia in primary
      care is not effective enough, especially with regard to early stages of dementia.
      Previous research results suggest that there are reservations among general
      practitioners towards dementia diagnostics. So far, however, the causes for this
      or the positions and strategies of general practitioners towards dementia care
      have not been sufficiently investigated. The aim of the study was to investigate
      the attitudes of general practitioners towards dementia diagnostics, to identify
      common challenges in day-to-day practice and to derive starting points for
      optimization. METHODS AND PARTICIPANTS: In the course of a survey, which was
      developed on the basis of a separate preliminary interview study, 425 general
      practitioners in Rhineland-Palatinate were interviewed (survey period: November
      2017 - January 2018). RESULTS: The results show that a considerable part of the
      doctors surveyed have withdrawn from dementia diagnostics and delegated the care
      of dementia patients exclusively to the medical specialist level. From the data
      material, various reservations and challenges can be summarized, which can be
      seen as barriers to the effectiveness of primary care for dementia patients: 1)
      Low self-efficacy perception towards dementia, 2) differential diagnosis as
      hurdle, 3) challenges in doctor-patient communication, 4) lack of remuneration,
      5) low involvement of practice staff members, 6) more negative attitudes towards
      dementia diagnosis due to lack of geriatric education, 7) limited cooperation
      with and knowledge of regional counseling and care services. DISCUSSION: Several
      starting points can be identified to further optimize the GP dementia diagnoses
      and care: 1) Increased awareness of options beyond therapeutic interventions, 2)
      differential diagnosis and care pathways, 3) doctor-patient communication, 4)
      remuneration and incentives, 5) involvement of practice staff members, 6) higher
      sensitivity due to geriatric education, 7) cooperation with and knowledge of
      dementia care and counseling services.

PMID- 30231279
TI  - [How do Doctors Manage Their Own Colorectal Cancer Screening and What Do They
      Recommend Their Patients? - Results of a Survey Under General Physicians and
      Internists].
AB  - INTRODUCTION: Screening programs efficiently reduce incidence of and mortality
      from colorectal cancer. Participation rates in Germany are still relatively low.
      By knowing how doctors manage their own colorectal cancer screening provides
      information how they estimate the potential of these strategies and what they
      recommend their patients. METHOD: A postal survey was conducted with 450 general
      physicians and internists aged above 50 years and registered at the KV
      Unterfranken. They received a questionnaire asking for their personal data, their
      own colorectal cancer screening and their attitude towards this topic and their
      patients. RESULTS: Based on 237 questionnaires received, 72 % of the doctors had
      undergone cancer screening. 81 % decided for colonoscopy. Convinced of the
      benefit of colorectal cancer screening 90 % of the respondents actively recommend
      their patients to participate screning programs. 88 % advise to undergo
      colonoscopy. CONCLUSION: A high percentage of physicians undergo colorectal
      cancer screening. Their high participation rate can be used as an additional
      motivating factor in colorectal cancer prevention campaigns.

PMID- 30231281
TI  - [Pain Treatment - Complex and Individual].

PMID- 30231280
TI  - [Diagnosis and Management of Adrenal Insufficiency].

PMID- 30231282
TI  - [34-Year-Old Patient with Scarred-Scaly Skin Changes].

PMID- 30231283
TI  - [Pharmacological Basis of Pain Treatment].
AB  - Many chronic diseases or their consequences are associated with pain.
      Furthermore, the pain itself can become the disease. Pharmaceuticals are an
      important component in the treatment of pain. This article presents different
      analgesic drugs, their mode of action, indications, dosage and adverse drug
      reactions.

PMID- 30231284
TI  - [Treatment-Refractory Pain].
AB  - Pain therapy concepts should be based on a biopsychosocial model. A prerequisite
      for adequate pain therapy is the detailed medical history. The questions about
      the intensity of pain and especially about the quality of pain are crucial for
      the selection of drug therapy. In addition to the questioning, targeted physical
      examination is essential. This should be repeated in case of therapy-refractory
      pain in the course. The transfer of clinically relevant knowledge about the
      emergence and the development of pain occurs in the new cross-sectional area 14
      "pain medicine" and has been anchored in the licensing regulations. Treatment
      refractory pain, despite adequate pharmacological therapy, may be the result of
      individual metabolism. For tumor-related pain, opioid rotation is a suitable
      symptom control procedure. To avoid treatment-refractory pain peaks, the
      medication for the need for basic medication should be adjusted in the dose. Non
      drug treatment should be targeted for treatment-refractory pain to promote
      patient's ownership. Physiotherapeutic measures have the goal of increasing the
      self-efficacy of pain and regaining confidence in one's own bodily functions.

PMID- 30231285
TI  - [Errors and Solutions During Medical Therapy for Chronic Pain].
AB  - Chronic pain is a main symptom of many diseases in internal medicine. The
      symptomatic treatment of pain in medical diseases is the task of the internist.
      Errors in drug therapy of pain can be reduced by a systematic approach of
      selection, application and monitoring of used medicine, taking effectiveness,
      duration, dose, comedication and safety into account.

PMID- 30231286
TI  - [Emergency sonography of the heart - step by step].

PMID- 30231287
TI  - [Hormone Replacement Therapy in Males].
AB  - Testosterone is a natural hormone which is essential to maintain physical and
      emotional wellbeing in men. Male hypogonadism is an endocrine condition of
      testosterone deficiency with the potential to cause multiple morbidities and
      psychosocial complaints. The condition can be of primary (testicular), secondary
      (hypothalamic-pituitary) or so-called functional origin (as a result of
      inflammatory conditions, obesity or chronic illness). Testosterone deficiency can
      cause symptoms of sexual nature, insulin resistance, osteoporosis, anemia among
      others. A replacement of testosterone should not be initiated in case of desired
      paternity, unclear processes of the prostate, mammary gland, or high hematocrit.
      Diagnosis and treatment as well as surveillance of the therapy of hypogonadism
      are clearly regulated by international guidelines and replacement therapy is
      proven to be effective to ameliorate the above-named complaints when performed
      according to these guidelines.

PMID- 30231288
TI  - Maternal Mortality in Brazil: Proposals and Strategies for its Reduction.

PMID- 30231289
TI  - Risk Assessment for Preterm Delivery using the Fetal Fibronectin Test Associated
      with the Measurement of Uterine Cervix Length in Symptomatic Pregnant Women.
AB  - OBJECTIVE:  To analyze the use of the measurement of uterine cervix length (MUCL)
      and the fetal fibronectin (fFN) rapid test as predictors of preterm delivery
      (PTD) in symptomatic pregnant women assisted at the Santa Casa de Misericordia de
      Sobral Maternity Hospital. METHODS:  This was a prospective and analytic study
      involving 53 parturients assisted between September of 2015 and July of 2016; the
      participants were between 24 and 34 weeks of gestational age (GA) and presented
      complaints related to preterm labor (PTL) prodromes. Vaginal secretion was
      collected for fFN testing, and the MUCL was obtained via transvaginal
      ultrasonography. RESULTS:  A total of 58.49% of the subjects showed MUCL < 25 mm,
      and 41.51% were positive in the fFN rapid test. A total of 48 patients were
      followed-up until their delivery date, and 54.17% resulted in PTL. The relative
      risk (RR) for PTD in patients with MUCL < 25 mm was 1.83 (p = 0.09, 0.99-3.36,
      95% confidence interval [CI]), with a mean time before delivery of 2.98 weeks.
      Based on fFN positive results, the RR was 3.50 (p = 0.002, 1.39-8.79, 95%CI) and
      the mean time until delivery was 1.94 weeks. The RR was 2.70 (p = 0.002, 1.08
      6.72, 95%CI) when both tests were used. The RR of PTD within 48 hours, and 7 and
      14 days were, respectively, 1.30 (p = 0.11, 95% CI 1.02-1.67), 1.43 (p = 0.12,
      95% CI % 0.99-2.06), and 2.03 (p = 0.008, 95% CI 1.26-3.27), when based on the
      MUCL, and 1.75 (p = 0.0006, 95% CI 1.20-2.53), 2.88 (p = 0.0001, 95% CI, 1.57
      5.31), and 3.57 (p = 0.0002, 95% CI 1.63-7.81) when based on positive fFN
      results. The RR at 48 hours and 7 and 14 days considering both tests was 1.74 (p
      = 0.0001, 95% CI 1.14-2.64), 2.22 (p = 0.0001, 95% CI 1.22-4.04), and 2.76 (p =
      0.0002, 95% CI 1.27-5.96), respectively. CONCLUSION:  In symptomatic pregnant
      women, we concluded that the MUCL < 25 mm associated with positive fFN rapid test
      indicate increased the risk for PTD. Further studies with larger sample sizes
      could contribute in supporting the results presented in the current study.

PMID- 30231290
TI  - Shared Oocyte Donation: Ideas and Expectations in a Bioethical Context Based on a
      Qualitative Survey of Brazilian Women.
AB  - OBJECTIVE:  Assisted reproduction combines innovative technologies and new forms
      of procreation through gamete donation; however, it also leads to moral and
      ethical issues and to the wide application of referential bioethics. The
      objective of the present study was to understand the bioethical context of shared
      oocyte donation. METHODS:  The present qualitative study used the Collective
      Subject Discourse methodology to interview donors and recipients in Brazil.
      RESULTS:  Donors suffer from infertility, and in vitro fertilization opens the
      possibility of having a child; however, the cost is high, and helping the
      recipient is more important than the financial cost. The recipients regret
      delaying motherhood; adopting a child is their last option, and they desire to
      feel the physical stages of pregnancy. The recipients find the rules unfair
      regarding the lack of an oocyte bank and the fact that the treatment must be
      performed in shared cycles; however, oocyte donation makes it possible to realize
      the common dream of motherhood. CONCLUSION:  The obtained data showed that the
      patients are suffering and frustrated due to infertility, and they realize that
      in vitro fertilization may be the treatment they need. These women believe that
      children are essential in the constitution of the family, and scientific advances
      bring about innovative technologies and new forms of family constitution, with
      repercussions in the social, economic, political, and family contexts that lead
      to bioethical questions in Postmodernity.

PMID- 30231291
TI  - Quality Information about Uterine Fibroids on the Internet.
AB  - OBJECTIVE:  There are no published studies analyzing the quality of the
      information for lay women on the Internet regarding uterine fibroids. The
      accuracy of the provided material is also unknown. Thus, we have performed a
      cross-sectional study with 381 websites in the English and Brazilian Portuguese
      languages between May and December 2017. METHODS:  Two investigators performed
      the analysis, and the Cohen kappa coefficient was calculated to analyze the
      agreement between them. Search terms (uterine fibroids and derivatives) in the
      English and Brazilian Portuguese languages were used. The accuracy was analyzed
      by a 10-item checklist created based on the American Society for Reproductive
      Medicine (ASRM), National Institutes of Health (NIH) and European Menopause and
      Andropause Society (EMAS) consensuses about uterine fibroids. The item-test
      correlation and the intraclass coefficient were performed in the 16 questions
      from the DISCERN instrument, which was designed to measure the quality of health
      information on the Internet. Analysis of variance (ANOVA) measurements were
      performed for the independent variables and the DISCERN/accuracy scores. RESULTS:
      Google was the most used search engine, and uterine fibroid was the search term
      that generated most of the analyzed material. The median score for accuracy in
      all websites was 5 out of 10, and the median score of the DISCERN instrument was
      38 out of 80. The top-scoring sites in the English language were derived from
      scientific organizations and federal governments, and they regarded the DISCERN
      score (The American College of Obstetricians and Gynecologists [ACOG], the Food
      and Drug Administration [FDA]) and the accuracy criteria (NIH, and FDA). On the
      other hand, in the Brazilian Portuguese language, the highest scores in both
      instruments were from magazines or physician's blogs. The Cronbach alpha test
      showed a higher correlation (0.77-0.79) between the sites and DISCERN; however,
      the item-test correlation varied from 0.39 to 0.56. CONCLUSION:  There is a need
      to improve the quality of the information regarding uterine fibroids for lay
      women.

PMID- 30231292
TI  - Urinary Incontinence and Quality of Life in Female Patients with Obesity.
AB  - OBJECTIVE:  To analyze the prevalence of urinary incontinence (UI) in female
      patients with an indication for bariatric surgery, to investigate the potential
      risk factors and the impact on quality of life. METHODS:  A cross-sectional study
      with female patients with obesity. The evaluation consisted of a structured
      interview, a specific study form and quality of life questionnaires. The Poisson
      regression was performed to identify independent risk factors related to UI.
      RESULTS:  A total of 221 patients were enrolled; 118 of the study participants
      (53.4%) reported UI episodes. Mixed UI (MUI), stress UI (SUI) only, and urgency
      UI (UUI) only were reported by 52.5% (62), 33.9% (40) , and 13.5% (16) of these
      patients respectively. The prevalence of UI was increased by 47% among the women
      who had given birth vaginally and by 34% of the women who had entered menopause.
      Vaginal delivery and menopause were identified as independent risk factors
      related to UI. The mean International Consultation on Incontinence Questionnaire 
      Short Form (ICIQ-SF) score was 9.36 +/- 4.9. The severity of symptoms was
      considered moderate in 53.3% (63) of the patients with UI. CONCLUSION:  Urinary
      incontinence impacts quality of life negatively, and the prevalence of UI is high
      among obese patients. In the present study, vaginal delivery and menopause were
      independently associated with UI.

PMID- 30231293
TI  - Sexually Transmitted Infections Detected by Multiplex Real Time PCR in
      Asymptomatic Women and Association with Cervical Intraepithelial Neoplasia.
AB  - OBJECTIVE:  To determine the frequency of sexually transmitted infections (STIs)
      in asymptomatic women and the association of STIs with cervical intraepithelial
      neoplasia (CIN). METHODS:  A cross-sectional study was performed, enrolling women
      examined in a general gynecology clinic and in a colposcopy referral center from
      October 2014 to October 2015. The colposcopy group consisted of 71 women, and the
      general gynecology group consisted of 55 women. Cervical samples were collected
      for cervical cytology and a multiplex real-time polymerase chain reaction (PCR)
      was developed to detect human papillomavirus (HPV) and the STIs caused by the
      following microorganisms: Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma
      genitalium, Ureaplasma urealyticum, and Neisseria gonorrhoeae. A multivariate
      analysis was performed by logistic regression, considering the significance level
      of 0.05. RESULTS:  The general frequency of STIs was: 46.8% (HPV); 27.8% (C.
      trachomatis); 28.6% (M. genitalium); 0.8% (M. hominis); 4.8% (U. urealyticum);
      and 4.8% (N. gonorrhoeae). The significant risk factors for CIN were: HPV
      infection (odds ratio [OR] = 2.53; p = 0.024); C. trachomatis (OR = 3.04; p =
      0.009); M. genitalium (OR = 2.37; p = 0.04); and HPV and C. trachomatis
      coinfection (OR = 3.11; p = 0.023). After the multivariate analysis, a
      significant association was found between HPV and CIN (OR = 2.48; 95% confidence
      interval [95%CI]: 1.04-5.92; p = 0.04); and between C. trachomatis and CIN (OR =
      2.69; 95%CI: 1.11-6.53; p = 0.028). CONCLUSION:  The frequency of STIs was high
      in asymptomatic patients. Infections by HPV and C. trachomatis were independently
      associated with the presence of CIN. The high frequency of STIs in asymptomatic
      women suggests the need for routine screening of these infections.

PMID- 30231294
TI  - Multiple Pregnancy: Epidemiology and Association with Maternal and Perinatal
      Morbidity.
AB  - Twin pregnancy accounts for 2 to 4% of total births, with a prevalence ranging
      from 0.9 to 2.4% in Brazil. It is associated with worse maternal and perinatal
      outcomes. Many conditions, such as severe maternal morbidity (SMM) (potentially
      life-threatening conditions and maternal near-miss) and neonatal near-miss (NNM)
      still have not been properly investigated in the literature. The difficulty in
      determining the conditions associated with twin pregnancy probably lies in its
      relatively low occurrence and the need for larger population studies. The use of
      the whole population and of databases from large multicenter studies, therefore,
      may provide unprecedented results. Since it is a rare condition, it is more
      easily evaluated using vital statistics from birth e-registries. Therefore, we
      have performed a literature review to identify the characteristics of twin
      pregnancy in Brazil and worldwide. Twin pregnancy has consistently been
      associated with SMM, maternal near-miss (MNM) and perinatal morbidity, with still
      worse results for the second twin, possibly due to some characteristics of the
      delivery, including safety and availability of appropriate obstetric care to
      women at a high risk of perinatal complications.

PMID- 30231295
TI  - Vesicouterine Fistula (Youssef Syndrome): Case Report and Literature Review.
AB  - OBJECTIVE:  To describe a case of vesicouterine fistula and to review the
      literature related to this condition. METHODS:  For the review, we accessed the
      MEDLINE, BIREME and LILACS databases; the references of the searched articles
      were also reviewed. RESULTS:  A 38-year-old woman, in the 1st day after her 3rd
      cesarean, presented heavy hematuria, which was considered secondary to a
      difficult dissection of the bladder. A total of 6 months after delivery, she
      failed to resume her regular menstrual cycles and presented cyclic menouria and
      amenorrhea. At this time, she had two episodes of urethral obstruction by blood
      clots. She remained without a correct diagnosis until about two years
      postdelivery, when a vesicouterine fistula was confirmed through cystoscopy. A
      surgical correction through open abdominal route, coupled with hysterectomy, was
      performed. After the surgery, the symptoms disappeared. The review showed a
      tendency of change in the relative frequency of the different types of
      genitourinary fistulae. Vesicovaginal fistulae, usually caused by inadequate care
      during labor, are becoming less frequent than those secondary to medical
      procedures, such as vesicouterine fistulae. The most common cause of this latter
      kind of fistula is cesarean section, especially repeated cesarean sections. The
      diagnosis is confirmed through one or more imaging exams, or through cystoscopy.
      The most common treatment is surgical, and the routes are: open abdominal,
      laparoscopic, vaginal or robotic. There are some reports of success with the
      conservative treatment. CONCLUSION:  Vesicouterine fistulae are becoming more
      common because of the increase in the performance of cesarean sections, and the
      condition must be considered a possible complication thereof.

PMID- 30231296
TI  - Diagnosis of Atelosteogenesis Type I suggested by Fetal Ultrasonography and
      Atypical Paternal Phenotype with Mosaicism.
AB  - Atelosteogenesis type I (AOI) is an autosomal dominant skeletal dysplasia caused
      by mutations in the filaminB (FLNB) gene with classic and well-recognizable
      clinical findings. However, parents affected with a mild phenotype, probably with
      somatic mosaicism, can generate offspring with a much more severe phenotype of
      AOI. In the present report, we describe a female newborn with classic AOI leading
      to early neonatal death, whose diagnostic was based on prenatal radiological
      findings and on the physical examination of the father. Since her father had limb
      deformities and corporal asymmetry, suggesting somatic mosaicism, his biological
      samples were analyzed through a gene panel for skeletal dysplasias. A missense
      mutation not previously described in the literature was detected in the FLNB
      gene, affecting ~ 20% of the evaluated cells and, therefore, confirming the
      diagnosis of mosaic AOI in the father. The molecular analysis of the father was
      crucial to suggest the diagnosis of AOI in the newborn, since she died early and
      there were no biological samples available.

PMID- 30231298
TI  - Investigation of Different Ways in Which the CODIS 7.0 May be Used in Mass
      Disaster Identification.
AB  - DNA analysis is a key method for the identification of human remains in mass
      disasters. Reference samples from relatives may be used to identify missing
      persons by kinship analysis. Different methods of applying the CODIS in disaster
      victim identification (DVI) were investigated. Two searches were evaluated: (i)
      relating family relatives to a pedigree tree (FPT) and (ii) relating unidentified
      human remains to a pedigree tree (UPT). A joint pedigree likelihood ratio (JPLR)
      and rank were calculated for each search. Both searches were similar in average
      JPLR and rank. In exceptional cases, namely the existence of a mutation different
      from the CODIS model, a nonbiological father, a mistake in STR, or incorrect
      profile association, the UPT search returned one true rank, whereas the FPT
      search returned no results. This paper suggests a novel strategy to overcome
      these limitations and increase efficiency in conducting identification of mass
      disaster victims.

PMID- 30231297
TI  - High MDR-1 expression by MAIT cells confers resistance to cytotoxic but not
      immunosuppressive MDR-1 substrates.
AB  - High expression of the ATP-binding cassette-multi-drug efflux protein 1 (MDR1) is
      a striking feature of mucosal-associated invariant T (MAIT) cells, a prominent
      human innate-like T cell subset. We demonstrate significantly higher MDR1
      expression by CD8 + CD161 ++ Valpha7.2 + MAIT cells than the phenotypically and
      functionally related CD8 + CD161 ++ Valpha7.2-subset and show MDR1 expression to
      be similarly high throughout MAIT CD4 + , CD8 + , double-negative (DN) and double
      positive (DP) cell subsets. We demonstrate the MAIT cell-predominant CD8+ CD161++
      subset to uniquely and efficiently efflux the cytotoxic anthracycline
      daunorubicin, retain function on daunorubicin exposure and demonstrate MDR1
      dependent protection from daunorubicin-induced apoptosis. By contrast, CD8+
      CD161++ Valpha7.2+ MAIT cells were not protected from the anti-proliferative and
      cytotoxic effects of the immunosuppressive MDR1 substrates tacrolimus and
      mycophenoic acid, although function following MAIT cell-specific T cell receptor
      (TCR)-dependent and -independent stimulation was preserved on in-vitro exposure
      to these agents. Overall, our data further define MDR1 expression by CD161++ T
      and MAIT cells and demonstrate the potential for high MDR1 expression by MAIT
      cells to confer resistance to cytotoxic MDR1 substrates in vivo . As our
      understanding of the importance of MAIT cells in human immunity and
      immunopathology grows, this is an important observation for clinical contexts
      such as the treatment of malignancy, autoimmunity and post-transplant
      immunosuppression.

PMID- 30231299
TI  - Early Signs of Fracture Repair in the Human Rib Cage: Implications for Forensic
      Casework.
AB  - The decomposed body of a woman discovered beneath a collapsed structure was
      examined at the C.A. Pound Human Identification Laboratory. Despite a mix of rib
      fractures with and without indications of healing, it is most likely that all
      fractures occurred as a result of a single, compressive event. Signs of
      intramembranous, and possibly direct, fracture healing at the incomplete
      fractures without signs of endochondral ossification at the complete fractures
      suggest the individual died very shortly-but not immediately-after injury. Given
      the case circumstances, the findings inform immediate cause of death. This case
      study highlights that differential healing as a result of a single event is
      possible. Further, it illustrates the importance of careful examination of micro
      discontinuities/cracks that can occur in association with major fractures.
      Fracture healing and dating data are discussed, as is the possible need for
      critical evaluation of the antemortem/perimortem boundary.

PMID- 30231300
TI  - Neuropsychological and Criminological Features of Female Homicide Offenders.
AB  - Few studies have examined life history and cognitive characteristics unique to
      female homicide offenders. Understanding these characteristics could aid in risk
      assessment for extreme violence in this group of offenders. The current study
      utilized t-tests or chi-square tests to compare 27 female and 81 male homicide
      offenders on psychiatric, neurologic, criminal, and cognitive characteristics.
      Additionally, we explored the role of abuse history in female offenders through
      Kruskal-Wallis or Fisher's exact tests. Results indicate that in comparison with
      male counterparts, females are more likely to have history of mood disorder,
      borderline personality disorder, and abuse. Cognitively, female homicide
      offenders exhibit circumscribed cognitive impairment in verbal abilities and
      perform similarly to male homicide offenders across most cognitive tasks. Within
      the female offender group, history of sexual abuse is associated with higher
      rates of impulsive homicide and poorer verbal abilities. These findings provide
      preliminary evidence for distinct factors associated with homicide in women.

PMID- 30231301
TI  - Red blood cell transfusion in acute pulmonary embolism.

PMID- 30231302
TI  - Lymphoscintigraphic Findings That Predict Favorable Outcome after
      Lymphaticovenous Anastomosis.
AB  - Radionuclide lymphoscintigraphy is an imaging technique used to radiologically
      evaluate the lymphatic system which can be utilized to evaluate signs of
      lymphatic obstruction that could be indication for lymphaticovenous anastomosis
      (LVA) operations. Our objective was to investigate and identify the radiographic
      signs in lymphoscinigraphy that predict favorable outcome after LVA. We
      retrospectively reviewed the medical charts of 80 patients with upper or lower
      limb lymphedema who underwent initial lymphoscintigraphy before LVA during the
      2011 to 2014 study period to evaluate statistical association between
      lymphoscintigraphic findings and the clinical result after LVA. Following LVA,
      clinical improvement was observed in 50 patients (48 female and 2 male) with no
      clinical improvement evident in the remaining 1 male and 29 females. Dilated
      lymph vessels and dermal backflow were identified as the abnormal finding in
      lymphoscintigraphy that were significantly correlated with improved clinical
      result after LVA. Our conclusion is that radionuclide lymphoscintigraphy prior to
      LVA is helpful in identifying patients for whom LVA is of benefit. Based on our
      findings, presence of dilated lymph vessels and presence of dermal backflow are
      significantly correlated with improved clinical result after LVA.

PMID- 30231303
TI  - A LYVE-1/CRSBP-1 Mutation in Inherited Primary Lymphedema.
AB  - Primary lymphedema is clinically and genetically heterogeneous with germline
      mutations identified in approximately 20 primary lymphedema genes. The lymphatic
      vessel endothelial hyaluronan receptor-1 (LYVE-1) gene, also known as cell
      surface retention sequence binding protein-1 (CRSBP-1), encodes the major
      hyaluronan receptor in lymphatic endothelia and is one of the most specific
      lymphatic vessel markers. However, the role of this lymphatic endothelial
      specific protein in the development of the lymphatic system and lymphatic
      diseases remains unclear. Here, we report a missense mutation c.18C>G (p.S6R) in
      exon 1 within the N-terminal extension domain (outside the hyaluronan binding
      region) of LYVE-1 in three generations of an inherited lymphedema family with or
      without clinical symptoms. Lymphatic imaging revealed a partial, weak and delayed
      enhancement of tortuous lymph collectors in the distal part of the lymphedematous
      lower limb. Our findings revealed that LYVE-1/CRSBP-1 mutation in primary
      lymphedema cases is connected with both structural and functional lymphatic
      defects.

PMID- 30231304
TI  - Parental Experience of Prenatal Diagnosis of Lymphatic Malformation.
AB  - Lymphatic malformations are a developmental anomaly arising from a somatic
      mutation in the lymphatic endothelial cells. This study investigated parental
      experiences associated with prenatal diagnosis of LM. Parents of 5 children
      diagnosed prenatally with LM were recruited from the Vascular Anomalies Clinic at
      the Royal Childrens Hospital, Melbourne. Ten in-depth semistructured interviews
      were conducted with each parent separately to explore their experiences and views
      at the time of diagnosis and immediately after childbirth. Transcribed interviews
      were coded and thematically analyzed. Parents experienced prenatal diagnosis of
      LM as an unexpected and traumatic event. The lack of adequate information and
      clear care pathway created confusion and added to the difficulty of understanding
      the impact of LM on the unborn child and what to expect after the child was born.
      Parents used the internet as the primary source of additional information;
      however, some parents found that information distressing. Differences between
      mothers and fathers were noted in terms of roles that each parent played and
      their emotional responses during pregnancy and the prenatal diagnosis. Closer
      connection between obstetric centers and specialized treatment clinics are
      suggested to facilitate better understanding of the LM impact on the unborn child
      and available treatment options after birth.

PMID- 30231305
TI  - Pedicled Vascularized Lymph Node Transfer Treats Lymphedema in Rat Hind Limb: A
      Simple Experimental Study Design.
AB  - Vascularized lymph node transfer is a new and promising technique for the
      physiologic treatment of lymphedema and several clinical and experimental studies
      have been conducted in recent years. However, the exact mechanism of vascularized
      lymph node transfer is still unknown. In this study, we aimed to investigate
      treatment efficacy through the design of a simple and feasible experimental
      lymphedema model for testing a vascularized lymph node transfer technique. After
      a pilot study, 30 male Sprague-Dawley rats were divided into two groups and
      lymphedema was induced in the hindlimb of both groups. In Group 1 (control, n=15)
      no treatment was applied while pedicled lymph node transfer was applied in Group
      2 (experimental, n=15). Model dynamics were assessed with lymphoscintigraphy,
      limb measurement, and histological analysis. A statistically significant limb
      circumference reduction at the ankle was seen on days 30 and 90 in Group 2 as
      compared to Group 1, p<0.05, and lymphatic tracer transport improved in 13 out of
      the 15 animals in Group 2. A statistically significant reduction in histological
      scores was achieved in Group 2, p<0.05. In this rat hindlimb lymphedema model,
      our vascularized lymph node transfer technique is an effective physiologic
      surgical treatment and represents a feasible experimental model for future
      studies.

PMID- 30231306
TI  - Top 50 Landmarks in Sentinel Lymph Node Imaging: A Bibliometric Analysis.
AB  - Bibliometric analysis can be utilized to identify the most influential literature
      and track the trajectory of the research development in a given area. The purpose
      of this study is to summarize the top 50 most-cited landmarks and to examine the
      recent advances in the field of sentinel lymph node imaging. Web of Science was
      searched to create a database of all English language scientific journals. This
      search was then cross referenced with a similar search term query of Scopus to
      identify articles that may have been missed on the initial search. Articles were
      ranked by citation counts and screened by two independent reviewers. Citations
      for the top 50 papers ranged from 2725 to 163 with a median of 240. 10 papers
      were cited more than 500 times. The articles were published between 1993 - 2009
      across 23 journals. Our study identifies intellectual milestones in Sentinel
      Lymph Node Imaging research, reflecting on the characteristics and quality of the
      most highly cited literature, and provides a list of the most influential
      references related to SLNI.

PMID- 30231307
TI  - Assessing the Value of Next-Generation Sequencing Tests in a Dynamic Environment.
AB  - Next-generation sequencing (NGS)-based technology has lowered the cost of cancer
      testing for genomic alterations and is now commercially available from a growing
      number of diagnostic laboratories. However, laboratories vary in the
      methodologies underlying their tests, the types and numbers of genomic
      alterations covered by the test, and the clinical annotation of the sequencing
      findings. Determining the value of NGS tests is dependent on whether it is used
      to support clinical trials or as a part of routine clinical care at a time when
      both the investigational drug pipeline and the list of U.S. Food and Drug
      Administration-approved or Compendium-listed therapeutics is in a high state of
      flux. Reimbursement policy for NGS testing by the Centers for Medicare & Medicaid
      is evolving as the value of NGS testing becomes more clearly defined for specific
      clinical situations. Patient care and clinical decisions-making are dependent on
      the oncologist's knowledge of when NGS testing has value. Here, we review
      principles and practice for NGS testing in this dynamic confluence of technology,
      cancer biology, and health care policy.

PMID- 30231308
TI  - Incorporating Immunotherapy Into the Treatment Strategies of B-Cell Adult Acute
      Lymphoblastic Leukemia: The Role of Blinatumomab and Inotuzumab Ozogamicin.
AB  - Monoclonal antibodies and bispecific antibody constructs hold considerable
      promise in improving the outcomes of patients with acute lymphoblastic leukemia
      (ALL). Antibody-drug conjugates such as inotuzumab ozogamicin and the bispecific
      T-cell engager blinatumomab represent novel antibody constructs that have shown
      substantial clinical activity in ALL. Although most studies have focused on the
      use of these agents in the salvage setting, incorporation of these antibodies
      into the frontline regimens is imperative to improve long-term survival for
      patients with ALL and to increase the cure rates of adult ALL to the levels
      achieved in the pediatric population.

PMID- 30231309
TI  - Precision Medicine in Non-Small Cell Lung Cancer: Current Standards in Pathology
      and Biomarker Interpretation.
AB  - Non-small cell lung cancer (NSCLC) has become a prominent example of precision
      medicine among solid tumor malignancies. Clinical management of NSCLC now depends
      on surgical, chemotherapeutic, and radiation treatment regimens based on
      pathologic findings and clinical staging as well as targeted therapies based on
      molecular profiling. As molecular testing becomes increasingly important,
      preserving tissue for this purpose while rendering an accurate histologic
      diagnosis becomes a key consideration, particularly in advanced-stage NSCLC, in
      which small biopsy samples or aspirates are often the only specimen available.
      Next-generation sequencing panels are a powerful method of providing information
      relevant for both standard-of-care and investigational treatment options.
      However, taking advantage of the abundance of information gleaned from these
      panels requires careful annotation, prioritization, and reporting of molecular
      findings and their clinical significance. Although molecular profiling has
      traditionally relied on direct sampling of neoplastic tissue, blood-based
      diagnostics now offer the potential to provide some clinically useful information
      noninvasively.

PMID- 30231310
TI  - Supportive Care in Lung Cancer: Improving Value in the Era of Modern Therapies.
AB  - Driven by a discipline-wide imperative to maximize patient centeredness and
      value, supportive care services have experienced remarkable growth and acceptance
      in oncology care. Two such services with a growing evidence base and examples of
      routine integration into usual oncology care are palliative care and integrative
      medicine. Both focus on the patient experience with cancer during and after
      cancer-directed treatments occur, from diagnosis through survivorship or end-of
      life care. With a frame of increasing value for all in the oncology care
      ecosystem, we highlight the evidence for how these two disciplines can improve
      the experience of patients with cancer and their loved ones. We further highlight
      how additional focus in palliative care and integrative medicine can continue to
      build toward a shared vision of high-value, high-quality cancer care.

PMID- 30231311
TI  - Practical Methods for Integrating Genetic Testing Into Clinical Practice for
      Advanced Prostate Cancer.
AB  - Recent advances clearly demonstrate the potential clinical relevance of germline
      genetic testing and somatic genomic profiling in identifying possible therapeutic
      and/or clinical trial options, particularly in advanced prostate cancer. In
      addition, if a germline genetic mutation/pathogenic variant is identified, there
      may be important family implications and possible life-saving changes to
      healthcare management. However, there is substantial debate and uncertainty about
      how best to offer genetic testing services, which tests to use, which patients to
      test, what sequence of testing, what timing, by whom, and with what kind of
      follow-up. To help address this new area of potential benefit and confusion, we
      provide a practical overview of recent advances, discuss options and
      considerations for both germline and somatic testing, and offer practical advice
      on what providers should understand before referring and/or ordering testing, key
      discussion points for patients and families, and available genetics resources.

PMID- 30231312
TI  - So Much Data, So Little Knowledge: Using Formal Logic to Aggregate Data and
      Interpret Information.
AB  - Formal logic is the use of symbols to structure how we make inferences such that
      the structure can be applied beyond specific cases. The structure of clinical
      trials and the values equation (value = outcomes/cost) lend themselves to
      evaluation using formal logic. Doing this demonstrates the unique position of
      randomized clinical trials as a defensible format for gathering information and
      identifies the shortcomings of historical controls and meta-analyses and
      retrospective studies using large databases. A practical example using literature
      on maintenance therapy in metastatic colorectal cancer is assessed. It is
      important to emphasize that value will be relative to a viewpoint, with many
      interested parties having competing values. This underscores the place of
      physicians and professional societies as putting patient values first.

PMID- 30231313
TI  - Tumor-Agnostic Drug Development.
AB  - Therapies designed to target cancers that harbor specific molecular signatures
      have reshaped the landscape of oncologic drug development, and advances in next
      generation sequencing have led to an increase in the identification of these
      alterations across tumor types. Tumor-agnostic trial designs, such as the "basket
      trial," have been developed as an approach to study the efficacy of these
      treatments and increase patient access, especially for patients whose tumors
      carry these alterations infrequently. We review key aspects of these genomically
      enriched trial strategies and their impact on drug development and approval.

PMID- 30231315
TI  - Personalizing Postoperative Treatment of Head and Neck Cancers.
AB  - Head and neck cancer (HNC) treatment is a complex multidisciplinary undertaking.
      Although overtreatment can result in functional and cosmetic defects,
      undertreatment can result in cancer recurrence. Surgery and chemoradiotherapy are
      both accepted standards for the curative intent treatment of locally advanced
      mucosal squamous cell carcinoma of the head and neck, but are often prioritized
      differently depending on the site of tumor origin (e.g., oral cavity/sinonasal
      vs. oropharynx/larynx), tumor burden, tumor biology, quality-life considerations,
      and patient preference. Regardless of modalities chosen, failure to cure remains
      a considerable problem in locally advanced disease. For patients treated with
      primary surgery, high-risk pathologic features portend higher recurrence rates,
      and adjuvant therapy can reduce these rates and improve outcomes. This report
      details which tumor- and nodal-related factors are indications for adjuvant
      therapy, examines the impact of tumor HPV status on adjuvant treatment paradigms,
      and considers which systemic therapies should be used for which patients when
      trimodality therapy is indicated.

PMID- 30231316
TI  - Beyond Chemotherapy: Checkpoint Inhibition and Cell-Based Therapy in Non-Hodgkin
      Lymphoma.
AB  - Immune-based treatment strategies, such as checkpoint inhibition and chimeric
      antigen receptor (CAR) T cells, have started a new frontier for treatment in non
      Hodgkin lymphoma (NHL). Checkpoint inhibition has been most successful in Hodgkin
      lymphoma, where higher expression of PD-L1 is correlated with better overall
      response rate. Combinations of checkpoint inhibition with various chemotherapy or
      biologics are in clinical trials, with initially promising results and manageable
      safety profiles. CAR T-cell therapies that target CD19 are a promising and
      attractive therapy for B-cell NHLs, with a product approved by the US Food and
      Drug Administration in 2017. Changes in the target, hinge, or costimulatory
      domain can dramatically alter the persistence and efficacy of the CAR T cells.
      The ZUMA trials from Kite used CD19-(CD28z) CAR T cells, whereas the TRANSCEND
      studies from Juno and the JULIET studies from Novartis used CD19-(4-1BBz) CARs.
      Despite the recent successes with CAR T-cell clinical trials, major concerns
      associated with this therapy include cytokine release syndrome, potential
      neurotoxicities, B-cell aplasia, loss of tumor antigen leading to relapse, and
      cost and accessibility of the treatment. Although first-generation CAR T-cell
      therapies have failed in solid malignancies, newer second- and third-generation
      CAR T cells that target antigens other than CD19 (such as mesothelin or B-cell
      maturation antigen) are being studied in clinical trials for treatment of lung
      cancer or multiple myeloma. Overall, immune-based treatment strategies have given
      oncologists and patients hope when there used to be none, as well as a new basket
      of tools yet to come with further research and development.

PMID- 30231317
TI  - Treatment of Primary Central Nervous System Lymphoma: From Chemotherapy to Small
      Molecules.
AB  - Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non
      Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal
      fluid (CSF) without evidence of systemic spread. PCNSL is an uncommon tumor, and
      only four randomized trials and one phase III trial have been completed so far,
      all in the first-line setting. The prognosis of patients with PCNSL has improved
      during the past few decades with the introduction of high-dose methotrexate (HD
      MTX), which now serves as the backbone of all first-line treatment regimens.
      Despite recent progress, results after treatment are durable in half of patients,
      and therapy can be associated with late neurotoxicity. Novel insights into the
      pathophysiology of PCNSL have identified the B-cell receptor (BCR) pathway as a
      key mechanism in the pathogenesis of PCNSL. The use of novel agents targeting
      components of the BCR pathway, namely the Bruton tyrosine kinase (BTK) inhibitor
      ibrutinib, and immunomodulatory drugs (IMIDs) like lenalidomide and pomalidomide,
      has so far been limited to patients who have recurrent/refractory PCNSL with
      promising high response rates. Within the past 5 years, there has been a peak in
      clinical trials investigating small molecules and novel reagents in the
      recurrent/refractory setting, including immune checkpoint inhibitors, IMIDs, and
      BTK and PI3K/AKT/mTOR inhibitors.

PMID- 30231314
TI  - Novel Quantitative Imaging for Predicting Response to Therapy: Techniques and
      Clinical Applications.
AB  - The current standard of Response Evaluation Criteria in Solid Tumors (RECIST)
      based tumor response evaluation is limited in its ability to accurately monitor
      treatment response. Radiomics, an approach involving computerized extraction of
      several quantitative imaging features, has shown promise in predicting as well as
      monitoring response to therapy. In this article, we provide a brief overview of
      radiomic approaches and the various analytical methods and techniques,
      specifically in the context of predicting and monitoring treatment response for
      non-small cell lung cancer (NSCLC). We briefly summarize some of the various
      types of radiomic features, including tumor shape and textural patterns, both
      within the tumor and within the adjacent tumor microenvironment. Additionally, we
      also discuss work in delta-radiomics or change in radiomic features (e.g.,
      texture within the nodule) across longitudinally interspersed images in time for
      monitoring changes in therapy. We discuss the utility of these approaches for
      NSCLC, specifically the role of radiomics as a prognostic marker for treatment
      effectiveness and early therapy response, including chemoradiation,
      immunotherapy, and trimodality therapy.

PMID- 30231318
TI  - Complexity of Delivering Precision Medicine: Opportunities and Challenges.
AB  - Precision medicine has emerged as a tool to match patients with the appropriate
      treatment based on the precise molecular features of an individual patient's
      tumor. Although examples of targeted therapies exist resulting in dramatic
      improvements in patient outcomes, comprehensive genomic profiling of tumors has
      also demonstrated the incredible complexity of molecular alterations in tissue
      and blood. These sequencing methods provide opportunities to study the landscape
      of tumors at baseline and serially in response to treatment. These tools also
      serve as important biomarkers to detect resistance to treatment and determine
      higher likelihood of responding to particular treatments, such as immune
      checkpoint blockade. Federally funded and publicly available data repositories
      have emerged as mechanisms for data sharing. In addition, novel clinical trials
      are emerging to develop new ways of incorporating molecular matched therapy into
      clinical trials. Various challenges to delivery of precision oncology include
      understanding the complexity of advanced tumors based on evolving "omics" and
      treatment resistance. For physicians, determining when and how to incorporate
      genetic and molecular tools into clinic in a cost-effective manner is critical.
      Finally, we discuss the importance of well-designed prospective clinical trials,
      biomarkers such as liquid biopsies, the use of multidisciplinary tumor boards,
      and data sharing as evidence-based medicine tools to optimally study and deliver
      precision oncology to our patients.

PMID- 30231319
TI  - New Treatment Algorithms in Hodgkin Lymphoma: Too Much or Too Little?
AB  - Hodgkin lymphoma treatment continues to evolve as new means of assessing response
      to treatment, new appreciation of important risk factors, and more effective
      therapeutic agents become available. Treatment algorithms integrating functional
      imaging now provide the opportunity to modify therapy during its delivery,
      allowing adjustment of duration and intensity of chemotherapy and rationale
      identification of patients who may benefit from the addition of therapeutic
      irradiation. Novel agents, including the antibody drug conjugate brentuximab
      vedotin and checkpoint inhibitors such as nivolumab and pembrolizumab can improve
      the effectiveness of treatment while keeping toxicity within acceptable limits.
      Carefully designed clinical trials permit the identification of superior
      approaches in which efficacy is enhanced and toxicity minimized. Clinicians
      treating patients with Hodgkin lymphoma now have access to novel treatment
      approaches, which will require detailed assessment of each patient and careful
      discussion of the goals and risks of treatment at the time of planning primary
      treatment, again during delivery of that treatment as data indicating ongoing
      effectiveness become available, at the conclusion of initial intervention, and,
      when the need arises, at the time of recurrence of disease.

PMID- 30231320
TI  - Cancer Care for Refugees and Displaced Populations: Middle East Conflicts and
      Global Natural Disasters.
AB  - Conflicts and natural disasters can cause major disruptions to people's lives.
      Media and news agencies usually focus on immediate consequences of these events,
      including loss of life and injuries, environmental and property destruction, and
      relief efforts. In this article, we will examine the effects of conflicts
      (focusing on in the Middle East) and global natural disasters on patients already
      diagnosed with cancer and on those who are diagnosed with cancer during and in
      the immediate aftermath of these events. We will review the limited literature,
      provide situational analysis, and discuss medical relief efforts, governmental
      readiness, and the role of United Nations agencies and international
      nongovernmental organizations. We will also discuss treatment of patients with
      cancer in the context of prolonged displacements and limited resources.

PMID- 30231321
TI  - Practical Considerations for Antibodies in Myeloma.
AB  - The development of the monoclonal antibodies daratumumab and elotuzumab has
      expanded treatment options for multiple myeloma and led to great improvement in
      patient outcomes. These agents have favorable safety profiles and synergize
      effectively with established agents used in the management of myeloma, namely
      immunomodulatory drugs and proteasome inhibitors. This article reviews the
      rationale for use of monoclonal antibodies in myeloma, current approved
      indications for daratumumab and elotuzumab, the manner in which these agents are
      used in the overall management of myeloma, and specific challenges associated
      with their use in the clinic. It also highlights other, emerging drug
      combinations that incorporate daratumumab or elotuzumab and profiles new
      therapeutic antibodies currently under development.

PMID- 30231322
TI  - Precision Medicine for Primary Central Nervous System Tumors: Are We There Yet?
AB  - In recent years, technologic advances have increased tremendously our
      understanding of the molecular characteristics and genetic drivers of a variety
      of brain tumors. These discoveries have led to paradigm shifts in the treatment
      of these tumor entities and may therefore have a considerable impact on the
      outcome of affected patients in the near future. Here, we provide a broad
      overview of recently discovered clinically actionable mutations that have been
      identified in three different primary brain tumors: gliomas, meningiomas, and
      craniopharyngiomas. We furthermore highlight the diagnostic and therapeutic
      implications of these findings and summarize recently published and ongoing
      trials.

PMID- 30231323
TI  - Management of Biochemically Recurrent Prostate Cancer: Ensuring the Right
      Treatment of the Right Patient at the Right Time.
AB  - Biochemically recurrent prostate cancer is an increasingly common disease state,
      with more than 25,000 cases occurring annually in the United States. Fortunately,
      progress continues to be made to more effectively identify metastatic disease,
      optimize existing therapies, and develop new technologies and therapeutic
      strategies for the timing and delivery of systemic treatments to improve
      outcomes. This review covers three topics related to the diagnosis and treatment
      of men with biochemical recurrence (BCR). First, we provide an update on the
      state of the rapidly evolving field of molecular imaging and its place in
      practice. Second, we describe validated clinicopathologic methods to risk
      stratify patients with biochemically recurrent disease, including new gene
      expression classifiers, to personalize postoperative radiotherapy (RT) timing.
      Last, we define our approach to optimal management with systemic therapy,
      including identifying the patients who may benefit most and balancing the
      duration and timing of treatment with consideration of the effect of therapy on
      quality of life (QOL) and medical complications associated with treatment.

PMID- 30231324
TI  - Using a Neoadjuvant Approach for Evaluating Novel Therapies for Patients With
      Breast Cancer.
AB  - Preoperative systemic therapy, though primarily used to downstage breast cancers,
      can offer, using pathologic complete response (pCR) as an endpoint, a rapid
      assessment of efficacy of a given therapeutic approach, particularly in triple
      negative (TNBC) and HER2-positive breast cancers. Recently, this approach
      resulted in the approval of pertuzumab for HER2-positive cancers, in a
      considerably quicker timeline than would have been possible with its assessment
      in the adjuvant setting. However, the use of preoperative systemic therapy
      remains controversial, as the higher response rates noted with newer approaches
      have not routinely translated into improved longer-term outcomes, nor have they
      been confirmed in larger adjuvant trials. Almost all trials have demonstrated
      that pCR is a robust prognostic marker in patients with TNBC and HER2-positive
      cancers, so part of this discrepancy may be due to inadequate power in the
      preoperative trials and/or due to the heterogeneous nature of breast cancers. PCR
      following preoperative chemotherapy is not prognostic in many hormone receptor
      (HR)-positive breast cancers, especially those with a luminal A phenotype, which
      typically has minimal response to chemotherapy. Given this lack of response to
      chemotherapy, there is considerable interest in the use of neoadjuvant endocrine
      therapy (NET). The rate of pCR to NET in HR-positive cancers is low, leading to
      the use of surrogate markers, including changes in Ki-67 and the preoperative
      endocrine prognostic index (PEPI) score, as biomarkers of efficacy. Overall, the
      use of neoadjuvant approaches offers a rapid assessment of efficacy of novel
      therapies and remains a useful research tool for drug evaluation.

PMID- 30231325
TI  - Next-Generation Novel Noninvasive Cancer Molecular Diagnostics Platforms Beyond
      Tissues.
AB  - In recent years, there has been a revolutionary expansion in technologic advances
      and therapeutic innovations in cancer medicine. Cancer diagnostics has begun to
      move away from a sole dependence on direct tumor tissue biopsy for cancer
      detection, diagnosis, and treatment monitoring. The need for improvement in
      molecular cancer diagnostics has never been more important, with not only the
      advent of cancer genomics and genomics-guided precision medicine but also the
      recent arrival of cancer immunotherapies. Owing to the practical limitations and
      risks associated with tissue-based biopsy diagnostics, novel noninvasive cancer
      diagnostics platforms have continued to evolve and expand in recent years.
      Examples of these platforms include the liquid biopsy, which is used to
      interrogate ctDNA or circulating tumor cells, proteomics, metabolomics, and
      exosomes; the urine biopsy, which is used to assay ctDNAs; saliva and stool
      biopsies, which are used for molecular genomics assays; and the breath biopsy,
      which measures volatile organic compounds. These next-generation noninvasive
      molecular diagnostics assays beyond tissues fundamentally transform the potential
      utilities of cancer diagnostics to enable repeat, prospective, and serial
      longitudinal "biopsies" to monitor disease response resistance and progression on
      therapies. Moreover, they allow continual interrogation and molecular in-depth
      analysis of the evolving tumor's pan-canceromics under therapeutic stress. These
      technological and diagnostic advances have already brought about paradigm
      changing next-generation cancer therapeutic strategies to enhance overall
      treatment efficacies. This article reviews the key noninvasive next-generation
      molecular diagnostics platforms beyond tissues, with emphasis on clinical
      utilities and applications.

PMID- 30231326
TI  - Ultimate Precision: Targeting Cancer but Not Normal Self-replication.
AB  - Self-replication is the engine that drives all biologic evolution, including
      neoplastic evolution. A key oncotherapy challenge is to target this, the heart of
      malignancy, while sparing the normal self-replication mandatory for health and
      life. Self-replication can be demystified: it is activation of replication, the
      most ancient of cell programs, uncoupled from activation of lineage
      differentiation, metazoan programs more recent in origin. The uncoupling can be
      physiologic, as in normal tissue stem cells, or pathologic, as in cancer.
      Neoplastic evolution selects to disengage replication from forward
      differentiation where intrinsic replication rates are the highest, in committed
      progenitors that have division times measured in hours versus weeks for tissue
      stem cells, via partial loss of function in master transcription factors that
      activate terminal-differentiation programs (e.g., GATA4) or in the coactivators
      they use for this purpose (e.g., ARID1A). These loss-of-function mutations bias
      master transcription factor circuits, which normally regulate corepressor versus
      coactivator recruitment, toward corepressors (e.g., DNMT1) that repress rather
      than activate terminal-differentiation genes. Pharmacologic inhibition of the
      corepressors rebalances to coactivator function, activating lineage
      differentiation genes that dominantly antagonize MYC (the master transcription
      factor coordinator of replication) to terminate malignant self-replication.
      Physiologic self-replication continues, because the master transcription factors
      in tissue stem cells activate stem cell, not terminal-differentiation, programs.
      Druggable corepressor proteins are thus the barriers between self-replicating
      cancer cells and the terminal-differentiation fates intended by their master
      transcription factor content. This final common pathway to oncogenic self
      replication, being separate and distinct from the normal, offers the favorable
      therapeutic indices needed for clinical progress.

PMID- 30231327
TI  - Addressing the Unintentional Consequences of Cancer Therapy With Novel
      Integrative Therapeutics.
AB  - There are 15.5 million cancer survivors in the United States because of, in part,
      improvements in therapy. As a result, there will be an increased burden of long-
      and late-term complications of cancer care, such as metabolic alterations. These
      metabolic changes will include alterations in bone resorption, obesity,
      hypercholesterolemia, and diabetes mellitus. The majority of cancer treatment
      related toxicities have focused on endocrine therapy; however, chemotherapy and
      supportive medications, such as steroids, contribute to the development of these
      disorders. Because of the chronicity of these metabolic changes and their impact
      on morbidity, cancer risk, and outcomes as well other negative effects, including
      musculoskeletal pain and vasomotor symptoms, alternative strategies must be
      developed. These strategies should include nonpharmacologic approaches. Here, we
      summarize metabolic changes secondary to cancer care and integrative approaches
      to help alleviate therapy-associated toxicities.

PMID- 30231328
TI  - Innovative Strategies: Targeting Subtypes in Metastatic Breast Cancer.
AB  - Metastatic breast cancer continues to be a life-threatening diagnosis that
      impacts hundreds of thousands of patients around the world. Targeted therapies
      are usually associated with less toxicity compared with cytotoxic chemotherapies
      and often induce response or durable disease control in estrogen receptor (ER)
      and/or HER2+ breast cancers. Drugs that target CDK 4/6 either alone or in
      combination with endocrine therapy have demonstrated substantial improvements in
      progression-free survival (PFS) compared with endocrine monotherapy. Most
      recently, PARP inhibitors have shown longer PFS compared with physician's choice
      of chemotherapy in BRCA-associated cancers, leading to the first U.S. Food and
      Drug Administration (FDA) approval of a targeted therapy with the potential to
      benefit a subgroup of patients with triple-negative breast cancer (TNBC).
      Finally, newer drug delivery strategies using antibody drug conjugates have also
      allowed a "targeted approach" to deliver moderate to extremely potent cytotoxins
      directly to sites of metastatic disease, with less toxicity.

PMID- 30231329
TI  - The American Society of Hematology and ASCO Curricular Milestones for Assessment
      of Fellows in Hematology/Oncology: Development, Reflection, and Next Steps.
AB  - The American Society of Hematology (ASH)/ASCO Curricular Milestones is a tool for
      assessment and teaching for fellows in hematology/oncology. The expectations of
      the Next Accreditation System of the Accreditation Council of Graduate Medical
      Education (ACGME) was developed over years from the creation of the six core
      competencies in 1999 to the current data-driven outcomes-based system. The
      current internal medicine subspecialty milestones (ACGME reporting milestones)
      follow the general rubric of the general internal medicine milestones. The
      ASH/ASCO curricular milestones were developed from the foundational elements of
      the specialty, and they are interwoven with the ACGME reporting milestones. The
      2017 ACGME Milestones Report shows that the milestones display progression in
      performance through clear anchors. Educational outcomes are available in many
      specialties. The internal medicine subspecialties have been given the opportunity
      to update the ACGME reporting milestones. The ACGME has acknowledged that these
      milestones may be different for each of the specialties. The program committees
      of ASH and ASCO agree that revision of the ACGME reporting milestones would
      decrease the overlap of domains, lack of clarity, and negative language that is
      present in version 1.0. ASH and ASCO are working with the ACGME and American
      Board of Internal Medicine (ABIM) to develop Curricular Milestones, version 2.0.

PMID- 30231330
TI  - Acute Myeloid Leukemia: The Good, the Bad, and the Ugly.
AB  - Acute myeloid leukemia (AML) was initially subdivided according to morphology
      (the French-American-British system), which proved helpful in pathologic
      categorization. Subsequently, clinical and genomic factors were found to
      correlate with response to chemotherapy and with overall survival. These included
      a history of antecedent hematologic disease, a history of chemotherapy or
      radiation therapy, the presence of various recurrent cytogenetic abnormalities,
      and, more recently, the presence of specific point mutations. This article
      reviews the biology and responses of one AML subgroup with consistent response
      and good outcomes following chemotherapy (core-binding factor leukemia), and two
      subgroups with persistently bad, and even ugly, outcomes (secondary AML and TP53
      mutated AML).

PMID- 30231331
TI  - Liquid Biopsy to Identify Actionable Genomic Alterations.
AB  - Liquid biopsy has been used extensively in solid malignancies to detect
      actionable driver mutations, to monitor treatment response, to detect recurrence,
      to identify resistance mechanisms, and to prognosticate outcome. Although many
      liquid biopsy sequencing platforms are being used, only five test kits have
      received government approval. We review representative literature on these
      government-approved liquid biopsy kits, which are primarily used to detect EGFR
      mutation in lung cancer and RAS ( KRAS, NRAS, BRAF) mutations in colorectal
      carcinoma. Another emerging use of single-gene liquid biopsy is to detect PIK3CA
      mutations and to understand resistance to hormonal blockade in breast and
      prostate cancers. The two most commonly used next-generation sequencing (NGS)
      liquid biopsy tests (Guardant 360, Guardant Health; FoundationACT, Foundation
      Medicine Inc.) are discussed. The ability and the applicability of NGS platform
      to detect tumor mutation burden are also addressed. Finally, the use of
      circulating tumor DNA (ctDNA) to detect minimal residual disease may be the most
      important use of ctDNA in the setting of tumor heterogeneity. The ability to
      identify "shedders" and "nonshedders" of ctDNA may provide important insight into
      the clinicopathologic characteristics of the tumor and portend important
      prognostic significance regarding survival.

PMID- 30231332
TI  - Global Approaches in Myeloma: Critical Trials That May Change Practice.
AB  - The treatment of multiple myeloma (MM) has changed dramatically in the past
      decade with the introduction of new drugs into therapeutic strategies both in the
      frontline and relapse settings. With the availability of at least six different
      classes of agents that can be combined in doublet, triplet, or even quadruplet
      regimens and used together with high-dose therapy and autologous stem cell
      transplantation, the choice of the optimal strategy at diagnosis and at relapse
      represents a challenge for physicians. Also problematic is the lack of trials
      addressing questions, such as sequencing or the duration of maintenance. This
      review will focus on the results of recent clinical trials both in the frontline
      and relapse settings that have induced changes in clinical practice and will
      discuss the impact of important ongoing trials. A specific section will discuss
      therapeutic strategies when new drugs are not available.

PMID- 30231333
TI  - Combination Immunotherapy Development in Melanoma.
AB  - Melanoma has been the most important cancer to drive immunotherapy development of
      solid tumors. Since 2010, immunotherapy has been revolutionized by the concept of
      breaking tolerance. It represents a major paradigm shift and marks the beginning
      of a new era. The impact of the first immune checkpoint inhibitors, anti-CTLA-4
      and anti-PD-1/anti-PD-L1, is unprecedented. In 7 years, it transformed advanced
      stage melanoma into a curable disease in over 50% of patients. Another major step
      has been the development of the combination of BRAF inhibitors plus MEK
      inhibitors in the treatment of BRAF-mutant melanomas. For the treatment of
      advanced disease, approvals were obtained for the immune checkpoint inhibitors
      ipilimumab (2011), nivolumab (2014), pembrolizumab (2014), the combination
      ipilimumab plus nivolumab (2015), and the oncolytic virus vaccine laherparepvec
      (2015). The combination dabrafenib plus trametinib for BRAF-mutant melanoma was
      approved in 2014, with similar success for other BRAF plus MEK inhibitor
      combinations. Because of its unique therapeutic index (high efficacy and low
      toxicity) anti-PD-1 agents (nivolumab and pembrolizumab) have now been placed at
      the center of practically all combination therapy development strategies in
      melanoma. Anti-PD-1 agents are the central molecule for combinations with a great
      variety of other immunotherapeutics such as immune checkpoint inhibitors,
      agonists, IDO inhibitors, macrophage polarizing agents, monoclonal antibodies,
      vaccines, targeted agents, chemotherapeutics, radiation therapy, and even
      microbiome modulators.

PMID- 30231334
TI  - State-of-the-Art Management of Germ Cell Tumors.
AB  - The state of the art management of germ cell tumors (GCT) in 2018 does not
      include novel agents targeting genomic alterations or exciting immunologic-based
      approaches but rather the avoidance of pitfalls in everyday practice. The
      relative rarity of GCT and high curability with correct management create the
      "perfect storm" for high-stakes errors to occur. This review focuses on several
      common pitfalls that should be avoided in staging and management of early-stage
      and advanced GCT in order to maximize patient outcomes. A particularly frequent
      misstep is to base treatment decisions on pre- rather than postorchiectomy tumor
      markers that, depending on marker directionality, can lead to either
      undertreatment with potentially inferior outcomes or overtreatment with excess
      toxicity. Another common mistake is the failure to consider the unique ability of
      GCT to differentiate and the distinct biology of teratoma (chemoresistance and
      lack of increased glucose uptake compared with normal tissue), which exerts a
      pervasive influence on nonseminoma management. This may lead to inappropriate use
      of PET scan to evaluate the postchemotherapy residual mass and, if negative, the
      conclusion that surgery is not needed whereas (FDG-negative) teratoma should be
      removed. It could also result in administration of additional unnecessary
      chemotherapy to patients with marker normalization but without robust
      radiographic response after 3 to 4 cycles of BEP. Finally, oncologists should
      strive to maintain standard chemotherapy doses, not substitute carboplatin for
      cisplatin, and refer to expert centers when expertise (e.g., RPLND) is not
      available locally in order to achieve optimal cure rates in advanced disease.

PMID- 30231335
TI  - The Epigenetic Landscape in the Treatment of Gynecologic Malignancies.
AB  - The care of patients with advanced-stage or recurrent endometrial, ovarian, and
      cervical cancer remains clinically challenging. Despite the identification of
      novel therapeutics and advancements in supportive care, survival outcomes have
      been relatively unchanged over the past decade. In addition to established
      genomic alterations and the contributions of the tumor microenvironment to cancer
      progression, epigenetic mechanisms have emerged as important contributors to
      gynecologic cancer progression. DNA methylation, histone modification, and
      noncoding RNA expression may be important contributors to disease initiation and
      progression and may represent novel therapeutic targets. This article reviews the
      epigenetic landscape of endometrial, ovarian, and cervical cancer, describing the
      state of the science and discussing potential clinical applications. To date, the
      role of epigenetic drugs in the treatment of gynecologic cancers remains unclear,
      although continued progress may inform future treatment modalities.

PMID- 30231336
TI  - Patient-Clinician Communication Is a Joint Creation: Working Together Toward Well
      Being.
AB  - Oncology clinicians face a monumentally difficult task: to guide patients on what
      may be the scariest and most unpleasant journey of their lives. They must
      preserve their patients' hope while at the same time giving them accurate
      information. And patients with cancer face a monumentally difficult task:
      navigating a path while confronting an often-terrifying disease. Communication
      between patients with cancer, their loved ones, and the treating clinicians
      presents many challenges. We must become better at communicating with each other;
      patients need easier access to information about their medical condition and
      their health care; and we must establish relationships that are stronger and more
      respectful, trusting, and empathic. If we are to deliver patient-centered or
      whole-person care, we must know who our patients are, what is important to them,
      and how they derive meaning in their lives. In this review, we discuss ASCO's
      first Patient-Clinician Communication guideline, the importance and value of
      patients having direct access to their medical record, and how to address
      spirituality and/or religion with patients with cancer.

PMID- 30231337
TI  - Precision Medicine Versus Population Medicine in Colon Cancer: From Prospects of
      Prevention, Adjuvant Chemotherapy, and Surveillance.
AB  - With the advances of technologic revolution that provides new insights into human
      biology, genetics and cancer, as well as advantages of big data which amasses
      large amounts of information for us to approach cancer treatment and prevention,
      we are facing challenges of organically combining data from studies based on
      general population and information from individual testing and setting out
      precisional recommendations in cancer diagnosis, prevention, and treatment. We
      are obligated to accelerate the adaptation of new scientific discoveries into
      effective treatments and prevention for cancer. In this review, we introduce our
      opinions on bringing knowledge of precision and population medicine together to
      guide our clinical practice from the prospects of colorectal cancer prevention,
      stage III colon cancer adjuvant therapy, and postsurgery surveillance.

PMID- 30231338
TI  - Progress Through Collaboration: An ASCO and U.S. Food and Drug Administration
      Workshop to Improve the Evidence Base for Treating Older Adults With Cancer.
AB  - Older adults represent the majority of patients diagnosed with cancer, yet the
      evidence base used to guide therapy for this growing segment of the population is
      limited compared with data available for younger adults. Information is
      particularly limited for adults commonly seen in practice, including those over
      age 75 and those with comorbidity or frailty. Efforts have been underway to raise
      awareness of this substantial gap in evidence and identify strategies to build an
      evidence base for older adults. Recently, the ASCO and the U.S. Food and Drug
      Administration convened a public workshop to address this issue. There is a need
      for innovative trial design to test the efficacy and tolerability of therapies
      among generalizable older adult populations. Incorporation of endpoints such as
      functional independence and quality of life as well as investigation of geriatric
      assessment-based treatment allocation strategies will be needed to individualize
      care planning. Strategies to increase trial enrollment need to be emphasized,
      including modernizing eligibility criteria, addressing patient and provider
      barriers to clinical trial enrollment, and consideration of incentives for
      patients, providers, and sponsors. Finally, investigation of real-world data and
      incorporation of patient-reported outcomes into the drug-development process may
      provide opportunities to build evidence related to treatment benefit and
      tolerance with an emphasis on the patient experience among older adults in
      diverse treatment settings.

PMID- 30231339
TI  - Understanding Utilization Management Policy: How to Manage This Increasingly
      Complex Environment in Collaboration and With Better Data.
AB  - As innovation in cancer care continues and newer costly therapies receive
      approval, utilization management will continue to grow as an important way that
      payers can attempt to control costs and value while providing service to their
      patients. Although utilization management may be necessary, it takes many forms
      and is optimized when it ensures appropriate patient access to services and
      minimizes administrative burdens of physicians and staff. These opportunities are
      best explored in collaboration with payers. Information systems today provide an
      excellent platform for data sharing to facilitate collaborative efforts between
      care delivery organizations and payers to optimize these efforts. As state and
      national policies differ regarding utilization management, it is important for
      clinicians to be both aware and involved.

PMID- 30231340
TI  - Multidisciplinary Management of Muscle-Invasive Bladder Cancer: Current
      Challenges and Future Directions.
AB  - The treatment of muscle-invasive bladder cancer (MIBC) is complex and requires a
      multidisciplinary collaboration among surgery, radiation, and medical oncology.
      Although neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) and
      lymph node dissection has been considered the standard treatment for MIBC, many
      patients are unfit for surgery or cisplatin-ineligible, and considerations for
      bladder-preservation strategies not only are increasingly recognized as optimal
      treatment alternatives, but also should feature in the range of management
      options presented to patients at the time of diagnosis. Apart from chemotherapy,
      immunotherapy has also been used with success in locally advanced and metastatic
      bladder cancer and is moving into the MIBC space. Prospective studies addressing
      trends in management that span systemic, surgical, and radiation options for
      patients are discussed in this article.

PMID- 30231341
TI  - Pain Management in the Era of the Opioid Crisis.
AB  - PRACTICAL APPLICATIONS Recognize patients at higher risk for nonmedical opioid
      use. Learn about screening for chemical coping risk. Diagnose nonmedical opioid
      use. Manage nonmedical opioid use in the clinical oncology setting. Understand
      clinical criteria for referral to supportive and palliative care teams.

PMID- 30231342
TI  - Molecular Subtypes and the Evolution of Treatment Decisions in Metastatic
      Colorectal Cancer.
AB  - Colorectal cancer (CRC) has clinically relevant molecular heterogeneity at
      multiple levels: genomics, epigenomics, transcriptomics, and microenvironment
      features. Genomic events acquired during carcinogenesis remain drivers of cancer
      progression in the metastatic setting. For example, KRAS and NRAS mutations
      define a population refractory to epidermal growth factor receptor monoclonal
      antibodies, BRAFV600E mutations associate with poor outcomes under standard
      therapies and response to targeted inhibitors in combinations, and HER2
      amplifications confer unique sensitivity to double HER2 blockade. Multiple rare
      gene alterations driving resistance to epidermal growth factor receptor
      monoclonal antibodies have been described, with substantial overlap in primary
      and acquired mechanisms, in line with a clonal selection process. In this
      context, sequential analysis of circulating tumor DNA has the potential to guide
      drug development in a treatment-refractory setting. Rare kinase fusion events and
      complex alterations in genes involved in DNA damage repair have been described,
      with emerging evidence for targetability. On the other hand, transcriptomic
      subtypes and pathway activation signatures have also shown prognostic and
      potential predictive value in metastatic CRC. These markers reflect stromal and
      immune microenvironment interactions with cancer cells. For example, the
      microsatellite instable or POLE ultramutant CRC population is particularly
      sensitive to immune checkpoint inhibitors, whereas tumors with a mesenchymal
      phenotype are characterized by activation of immunosuppressive molecules that
      mandate stratified development of novel immunotherapy combinations. Here, we
      review the expanding landscape of targetable oncogenic alterations and signatures
      in metastatic CRC and discuss the clinical implementation of novel molecular
      diagnostic tests.

PMID- 30231343
TI  - Lifestyle Modifications and Policy Implications for Primary and Secondary Cancer
      Prevention: Diet, Exercise, Sun Safety, and Alcohol Reduction.
AB  - Improved cancer treatments and cancer detection methods are not likely to
      completely eradicate the burden of cancer. Primary prevention of cancer is a
      logical strategy to use to control cancer while also seeking novel treatments and
      earlier detection. Lifestyle modification strategies to improve primary
      prevention and risk reduction for the development of cancer include choosing a
      healthy diet with an emphasis on plant sources, maintaining a healthy weight
      throughout life, being physically active, regularly using sunscreen and wearing
      protective clothing, limiting sun exposure during the hours of 10 AM to 2 PM,
      avoiding indoor tanning, and reducing or eliminating alcohol use. In addition to
      continued use of ongoing education of the public, health care providers, and
      cancer support communities, other policy and public health efforts should be
      pursued as well. Examples of supported and successful policy approaches are
      included in this article, including efforts to limit indoor tanning and improve
      community-wide interventions to reduce ultraviolet radiation exposure as well as
      to formally support various alcohol policy strategies including increasing
      alcohol taxes, reducing alcohol outlet density, improving clinical screening for
      alcohol use disorders, and limiting youth exposure to alcohol marketing and
      advertising. These prevention strategies are expected to have the largest impact
      on the development of melanoma as well as breast, colorectal, head and neck,
      liver, and esophageal cancers. The impact of these strategies as secondary
      prevention is less well understood. Areas of additional needed research and
      implementation are also highlighted. Future areas of needed research are the
      effects of these modifications after the diagnosis of cancer (as secondary
      prevention).

PMID- 30231344
TI  - Biology and Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine
      Tumors.
AB  - In recent years, there have been important scientific advances in the biologic
      characterization of neuroendocrine neoplasms and in their treatment. This review
      will describe these scientific advances, the evolving systemic treatment
      approaches, and important topics to be addressed in future research.

PMID- 30231345
TI  - New Era in the Management of Melanoma Brain Metastases.
AB  - The remarkable advances in the systemic therapy of metastatic melanoma have now
      extended the 1-year overall survival rate from 25% to nearing 85%. Systemic
      treatment in the form of BRAF-targeted therapy and immunotherapy is slowly but
      surely proving its efficacy in the treatment of metatstatic brain metastases
      (MBM). Single-agent BRAF inhibitors provide an intracranial response rate of 25%
      to 40%, whereas the combination of BRAFi/MEKi leads to responses in up to 58%.
      However, the durability of responses induced by BRAFi/MEKi seems to be even
      shorter than in extracranial disease. On the other hand, single-agent ipilimumab
      provides comparable clinical benefit in MBMs as it does in extracranial
      metastases. Single-agent PD-1 anitbodies induce response rates of approximately
      20%, and those responses appear durable. Similarly the combination of CTLA-4+ PD
      1 antibodies induces durable responses at an impressive rate of 55% and is safe
      to administer. Although the local treatment approaches with radiation and surgery
      remain important and are critically needed in the management of MBM, systemic
      therapy offers a new dimension that can augment the impact of those therapies and
      come at a potentially lower cost of neurocognitive impairment. Considerations for
      combining those modalities are direly needed, in addition to considering novel
      systemic combinations that target mechanisms specific to MBM. In this report, we
      will discuss the underlying biology of melanoma brain metastases, the clinical
      outcomes from recent clinical trials of targeted and immunotherapy, and their
      impact on clinical practice in the context of existing local therapeutic
      modalities.

PMID- 30231346
TI  - Latest Advances in the Diagnosis and Treatment of Large Granular Lymphocytic
      Leukemia.
AB  - Large granular lymphocyte (LGL) leukemia has been recognized in the World Health
      Organization classifications among mature T cell and natural killer cell
      neoplasms and is divided into three categories. Chronic T cell leukemia and
      natural killer cell lymphocytosis can be considered as a similar spectrum of an
      indolent disease characterized by cytopenias and autoimmune conditions. The last
      category, aggressive natural killer cell LGL leukemia is very rare, related to
      Epstein-Barr virus, and seen mainly in young Asian people. Clonal LGL expansion
      arises from chronic antigenic stimulation sustained by interleukin-15 and
      platelet-derived growth factor cytokine signal. Those leukemic cells are
      resistant to apoptosis, mainly because of constitutive activation of survival
      pathways including Jak/Stat, MapK, Pi3k-Akt, RasRaf-1, MEK1/ERK, sphingolipid,
      and NFkappaB. Stat3 constitutive activation is the hallmark of this
      lymphoproliferative disorder. Socs3 is downregulated, but no mutation could be
      found to explain this status. However, several somatic mutations, including
      Stat3, Stat5b, and tumor necrosis factor alpha-induced protein 3, have been
      demonstrated recently in LGL leukemia; they are identified in half of patients
      and cannot explain by themselves LGL leukemogenesis. Recurrent infections as a
      result of chronic neutropenia, anemia, and autoimmune disorders are the main
      complications related to LGL leukemia. Despite an indolent presentation, 10% of
      patients die, mainly because of infectious complications. Current treatments are
      based on immunosuppressive therapies. A better mechanistic understanding of LGL
      leukemia will allow future consideration of a personalized therapeutic approach
      perhaps based on Jak/Stat inhibitors, which may offer better results than current
      immunosuppressive therapy.

PMID- 30231347
TI  - Global Breast Cancer Research: Moving Forward.
AB  - Breast cancer is a major global health problem and major cause of mortality.
      Although mortality trends are declining in high-income countries, trends are
      increasing in low- and middle-income countries (LMICs). Addressing global breast
      cancer research is a challenging endeavor, as notable disparities and extremely
      heterogeneous realities exist in different regions across the world. Basic global
      cancer health care needs have been addressed by the World Health Organization's
      (WHO) proposed list of essential medicines and by resource-stratified guidelines
      for screening and treatment. However, specific strategies are needed to address
      disparities in access to health care, particularly access to new therapies.
      Discussions about global research in breast cancer should take into account the
      ongoing globalization of clinical trials. Collaboration fostered by well
      established research organizations in North America and Europe is essential for
      the development of infrastructure and human resources in LMICs so that
      researchers in these countries can begin to address regional questions. Specific
      challenges that impact the future of global breast cancer research include
      increasing the availability of trials in LMICs, developing strategies to increase
      patient participation in clinical trials, and creation of clear guidelines for
      the development of real-world evidence-based research. The main objective of this
      review is to encourage the discussion of challenges in global breast cancer
      research with the hope that collectively we will be able to generate workable
      proposals to advance the field.

PMID- 30231348
TI  - Management of Refractory Germ Cell Cancer.
AB  - Over the past 5 decades, the use of well-validated, guideline-based strategies
      has resulted in high cure rates in newly diagnosed patients with germ cell
      cancer. However, about 30% of those with metastatic disease at initial
      presentation will experience refractory disease. Salvage treatment is far more
      complex and less validated than first-line treatment because it is rare, patient
      cohorts are more heterogeneous, and prognostic factors seem to have greater
      impact. Prior to the initiation of any salvage treatment, several considerations
      must be made, including assessment of known prognostic factors and choice of the
      optimal salvage strategy. Evaluation of patients according to their disease
      biology, response to prior treatment, and the extent of their tumor burden at the
      time of salvage treatment is crucial for establishing the optimal salvage
      strategy. Patients with metastatic germ cell cancer in whom adequate cisplatin
      based first-line chemotherapy fails should be included in the ongoing randomized
      TIGER trial comparing conventional-dose chemotherapy with high-dose chemotherapy
      as first salvage treatment. Outside this trial, patients may be treated with
      conventional or high-dose chemotherapy depending on the presence or absence of
      adverse prognostic factors, availability of resources, and patient and physician
      preferences.

PMID- 30231349
TI  - Integrating Social Media in Modern Oncology Practice and Research.
AB  - The widespread adoption and diffusion of social media provides oncology
      professionals with a unique and unprecedented opportunity to engage with the
      public. However, there remains a paucity of literature examining how clinicians
      and researchers can effectively use social media to complement modern oncology
      practice and research. In this review, we dissect the benefits and risks of
      professional social media use in oncology and offer several best practices for
      clinicians and researchers to achieve effective engagement. We also describe how
      to participate constructively in Twitter conversations at the time of medical or
      scientific conferences. Additionally, we demonstrate how to communicate
      appropriately and safely with patients and families online. Finally, we explore
      the exciting and nascent field of social media research and highlight the need to
      investigate its potential value in personalized cancer medicine.

PMID- 30231350
TI  - The Landscape of CAR T Cells Beyond Acute Lymphoblastic Leukemia for Pediatric
      Solid Tumors.
AB  - Adoptive cell therapy with genetically modified T cells holds the promise to
      improve outcomes for children with recurrent/refractory solid tumors and has the
      potential to reduce treatment complications for all patients. Although T cells
      that express chimeric antigen receptors (CARs) specific for CD19 have had
      remarkable success for B-cell-derived malignancies, which has led to their
      approval by the U.S. Food and Drug Administration, CAR T cells have been less
      effective for solid tumors and brain tumors. Lack of efficacy is most likely
      multifactorial, but heterogeneous antigen expression; limited migration of T
      cells to tumor sites; and the immunosuppressive, hostile tumor microenvironment
      have emerged as major roadblocks that must be addressed. In this review, we
      summarize the clinical experience with CAR T-cell therapy for pediatric solid
      tumors, including brain tumors. In addition, we review strategies that have been
      and are being developed to enhance their antitumor activity.

PMID- 30231351
TI  - Filling the Gap: Creating an Outpatient Palliative Care Program in Your
      Institution.
AB  - Well-designed, randomized trials demonstrate that outpatient palliative care
      improves symptom burden and quality of life (QOL) while it reduces unnecessary
      health care use in patients with cancer. Despite the strong evidence of benefit
      and ASCO recommendations, implementation of outpatient palliative care,
      especially in community oncology settings, faces considerable hurdles. This
      article, which is based on published literature and expert opinion, presents
      practical strategies to help oncologists make a strong clinical and fiscal case
      for outpatient palliative care. This article outlines key considerations for how
      to build an outpatient palliative care program in an institution by (1) defining
      the scope and benefits; (2) identifying strategies to overcome common barriers to
      integration of outpatient palliative care into cancer care; (3) outlining a
      business case; (4) describing successful models of outpatient palliative care;
      and (5) examining important factors in design and operation of a palliative care
      clinic. The advantages and disadvantages of different delivery models (e.g.,
      embedded vs. independent) and different methods of referral (triggered vs.
      physician discretion) are reviewed. Strategies to make the case for outpatient
      palliative care that align with institutional values and/or are supported by
      local institutional data on cost savings are included.

PMID- 30231352
TI  - More Than 50 Subtypes of Soft Tissue Sarcoma: Paving the Path for Histology
      Driven Treatments.
AB  - Sarcomas are a diverse group of cancers with mesenchymal origin. Although
      sarcomas comprise less than 1% of cancers, there are more than 50 different
      subtypes that are quite different from one another in terms of both their biology
      and clinical behavior. Historically, the need for adequate patient numbers in
      clinical trials has pushed sarcoma researchers to lump these very different
      malignancies together and treat the patients using a "one-size-fits-all"
      approach. However, with improvements in our scientific understanding, we are
      finally ready for a histology-tailored therapeutic approach to these complex
      diseases. In this review, we discuss key advances in our understanding of the
      biology underlying selected sarcoma subtypes and how targeting these subtypes is
      relevant therapeutically with respect to both molecularly targeted agents as well
      as immunotherapy.

PMID- 30231353
TI  - Moving From Mutation to Actionability.
AB  - The diffusion of high-throughput next-generation sequencing technologies has
      sustained massive parallel sequencing of tumor tissue providing a deep insight
      into tumor biology and advancement of personalized medicine. A substantial number
      of targeted agents have been investigated in gynecologic cancer and some have
      received U.S. Food and Drug Administration approval, like PARP inhibitors in
      ovarian cancer, bevacizumab in ovarian and cervical cancers, and pembrolizumab in
      microsatellite-unstable or mismatch repair-deficient endometrial cancer. To
      improve effectiveness of targeted therapy, identification of predictive
      biomarkers able to guide the selection of the correct drug for the correct
      patient is crucial. Different limitations must be addressed to favor a more rapid
      implementation of a genotyping approach in treatment selection, such as the
      possibility to easily assess tumor heterogeneity and clonal evolution along the
      disease trajectory and the need for innovative trial designs like adaptive or
      basket trials incorporating molecular features as selection criteria. A deep dive
      into the genomic features of exceptional responders may also favor better
      understanding of tumor biology, mechanism of action of a specific target agent,
      and identification or predictive biomarkers for subsequent tailored studies.

PMID- 30231354
TI  - Telemedicine in Cancer Care.
AB  - Telemedicine uses telecommunications technology as a tool to deliver health care
      to populations with limited access to care. Telemedicine has been tested in
      multiple clinical settings, demonstrating at least equivalency to in-person care
      and high levels of patient and health professional satisfaction. Teleoncology has
      been demonstrated to improve access to care and decrease health care costs.
      Teleconsultations may take place in a synchronous, asynchronous, or blended
      format. Examples of successful teleoncology applications include cancer
      telegenetics, bundling of cancer-related teleapplications, remote chemotherapy
      supervision, symptom management, survivorship care, palliative care, and
      approaches to increase access to cancer clinical trials. Telepathology is
      critical to cancer care and may be accomplished synchronously and asynchronously
      for both cytology and tissue diagnoses. Mobile applications support symptom
      management, lifestyle modification, and medication adherence as a tool for home
      based care. Telemedicine can support the oncologist with access to interactive
      tele-education. Teleoncology practice should maintain in-person professional
      standards, including documentation integrated into the patient's electronic
      health record. Telemedicine training is essential to facilitate rapport, maximize
      engagement, and conduct an accurate virtual exam. With the appropriate
      attachments, the only limitation to the virtual exam is palpation. The national
      telehealth resource centers can provide interested clinicians with the latest
      information on telemedicine reimbursement, parity, and practice. To experience
      the gains of teleoncology, appropriate training, education, as well as paying
      close attention to gaps, such as those inherent in the digital divide, are
      essential.

PMID- 30231355
TI  - Beyond the Knife: The Evolving Nonsurgical Management of Oligometastatic
      Colorectal Cancer.
AB  - In patients with liver-limited oligometastatic disease, the goal of treatment can
      be curative intent. Historically, this was accomplished in patients presenting
      with upfront resectable disease. The availability of increasingly efficacious
      chemotherapy and biologic combinations with encouraging response rates led to the
      potential to convert unresectable disease to resectability. Beyond the backbone
      of surgery, we now have a portfolio of locoregional strategies to consider.From
      an interventional radiology perspective, the use of portal vein embolization can
      facilitate hypertrophy of the liver in anticipation of resection, thus converting
      unresectable disease to one amenable to a surgical approach with curative intent.
      Technological advances in liver-directed ablative therapies have afforded the
      possibility of eliminate radiographically evident disease with the hope for long
      term disease control. Advanced radiotherapy techniques are further increasing the
      therapeutic options for patients with metastatic colorectal cancer. Improvements
      in external-beam radiotherapy over the past 2 decades include image-guided
      radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy,
      and proton-beam therapy. Finally, selective internal radiation therapy (SIRT)
      with microspheres labeled with the beta-emitter 90Y enable targeted delivery of
      radiation to hepatic tumors. A coordinated multidisciplinary approach is required
      to integrate these nonsurgical adjuncts in an evidence-based manner to optimize
      outcomes for patients with potentially resectable metastatic disease. In this
      article, we summarize recent developments in systemic therapy, radiotherapy, and
      interventional liver-directed therapies that have changed the treatment landscape
      for patients with oligometastatic colorectal cancer.

PMID- 30231356
TI  - Systemic Therapy for Advanced Urothelial Carcinoma: Current Standards and
      Treatment Considerations.
AB  - Urothelial carcinoma is the sixth most common malignancy in the United States.
      Although most are diagnosed with non-muscle-invasive malignancy, many patients
      will develop recurrent disease within 5 years, with 10% to 20% developing
      advanced muscle-invasive or more distant incurable disease. For such patients,
      clinical outcomes have remained suboptimal, although recent therapeutic advances
      have brought new hope to the field. Here, we discuss the main systemic treatment
      options available for the treatment of patients with advanced disease. This
      review begins with traditional chemotherapy, which remains a first-line treatment
      option for many patients. The second section focuses on the evolving landscape of
      immunotherapy, specifically on approved checkpoint inhibitors and future
      challenges. Last, we address advances in targeted treatments, including
      angiogenesis and fibroblast growth factor receptor (FGFR) inhibitors as well as
      antibody-drug conjugates. As the number of available treatment options continues
      to expand, ongoing trials to investigate the best sequence and combination
      strategies to incorporate these drugs into clinical practice will help delineate
      the future.

PMID- 30231357
TI  - Advances in Fertility Preservation for Young Women With Cancer.
AB  - Female patients of reproductive age with cancer often require treatment that can
      compromise their future fertility. Treatment-related infertility is an important
      cancer survivorship issue and is associated with depression and diminished
      quality of life. Recent advances in reproductive health care provide the
      opportunity to preserve fertility prior to the initiation of cancer therapy.
      Clinical guidelines recommend that oncology providers counsel patients about the
      risk of treatment-related infertility and fertility preservation options, and
      that they refer those who are interested in fertility preservation to fertility
      specialists. Guidelines endorse the use of assisted reproductive techniques (ART)
      provided by reproductive endocrinologists to preserve fertility in young female
      patients with cancer. In addition, ovarian suppression with gonadotropin
      releasing hormone (GnRH) agonists may be considered for ovarian protection during
      chemotherapy. This article reviews currently available and emerging ART for
      fertility preservation in female patients of reproductive age with cancer and
      current data supporting the use of ovarian suppression for ovarian protection
      during chemotherapy in this population. We also review the uptake of fertility
      services and discuss barriers to fertility preservation in female patients of
      reproductive age with cancer.

PMID- 30231358
TI  - Where We Stand With Immunotherapy in Colorectal Cancer: Deficient Mismatch
      Repair, Proficient Mismatch Repair, and Toxicity Management.
AB  - With the recent U.S. Food and Drug Administration approvals of pembrolizumab and
      nivolumab for refractory deficient mismatch repair metastatic colorectal cancer,
      immune checkpoint inhibitors have now entered into clinical care for
      gastrointestinal cancers. Extensive ongoing efforts are exploring additional
      combinations of therapy in both deficient and proficient mismatch repair
      colorectal cancer. This review will outline the current status of such efforts
      and discuss the critical aspects of recognition and management of immune-related
      toxicities from checkpoint inhibitors.

PMID- 30231359
TI  - Global Epidemiology, Prevention, and Management of Hepatocellular Carcinoma.
AB  - The incidence rate of hepatocellular carcinoma (HCC) is rising. It is one of the
      most common cancers worldwide and accounts for substantial morbidity and
      mortality. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus
      (HCV) infection, and nonalcoholic fatty liver disease (NAFLD) are the most
      important etiologies of HCC, and effective screening and management strategies
      are crucial to reduce the HCC risk. For HBV, which accounts for the majority of
      HCC cases, most infections were acquired via perinatal and early horizontal
      transmission. Universal vaccination of newborns has led to a decline in HCC
      incidence compared with the pre-vaccination era. Effective antiviral therapies
      with nucleos(t)ide analogues or pegylated interferon reduced the incidence of
      HCC. For HCV, the emergence of effective direct-acting antiviral (DAA) agents has
      substantially improved cure rates; therefore all patients with HCV should be
      considered for DAA treatment. The most important obstacle in eliminating HCV is
      access to therapy. For NAFLD, the global incidence is increasing rapidly, thus
      its impact on HCC incidence may be explosive. Progression to HCC in NAFLD happens
      particularly in those with nonalcoholic steatohepatitis (NASH) and exacerbated by
      metabolic syndrome, or PNPLA3 gene polymorphism. Lifestyle changes are imperative
      while drug therapy has yet to demonstrate substantive protective effects on HCC
      prevention. For management of HCC, early diagnosis via imaging surveillance among
      persons with HCC risk factors remains the most important strategy to identify
      early-stage disease appropriate for resection or transplantation.

PMID- 30231360
TI  - Is There a Precise Adjuvant Therapy for Esophagogastric Carcinoma?
AB  - Esophagogastric cancer remains a leading cause of cancer-related mortality
      worldwide. The prognosis for patients with locally advanced disease is poor and
      the majority of patients with operable tumors treated with surgery alone will
      have recurrent disease. A multimodal approach to treatment with adjunctive
      chemotherapy or chemoradiotherapy is therefore the standard of care for these
      patients. However, there is no global consensus on the optimal treatment strategy
      and international guidelines vary. National clinical trials inform local
      practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy
      combinations are all possible treatment options in the management of resectable
      esophagogastric cancer. A number of clinical trials are ongoing, which seek to
      directly compare multimodal treatment options and hope to provide clarity in this
      area. Furthermore, increased understanding of the molecular and genetic features
      of esophagogastric cancer may help to guide management of operable disease by
      determining optimal patient selection through identification of predictive
      biomarkers of response and the application of novel targeted agents.

PMID- 30231361
TI  - Preventing Treatment-Related Functional Decline: Strategies to Maximize
      Resilience.
AB  - The majority of patients with cancer are older adults. A comprehensive geriatric
      assessment (CGA) will help the clinical team identify underlying medical and
      functional status issues that can affect cancer treatment delivery, cancer
      prognosis, and treatment tolerability. The CGA, as well as more abbreviated
      assessments and geriatric screening tools, can aid in the treatment decision
      making process through improved individualized prediction of mortality, toxicity
      of cancer therapy, and postoperative complications and can also help clinicians
      develop an integrated care plan for the older adult with cancer. In this article,
      we will review the latest evidence with regard to the use of CGA in oncology. In
      addition, we will describe the benefits of conducting a CGA and the types of
      interventions that can be taken by the interprofessional team to improve the
      treatment outcomes and well-being of older adults.

PMID- 30231362
TI  - "My Patient Was Diagnosed With Nontargetable Advanced Non-Small Cell Lung Cancer.
      What Now?" Diagnosis and Initial Treatment Options for Newly Diagnosed Patients
      With Advanced NSCLC.
AB  - Although lung cancer remains the leading cause of cancer-related mortality in the
      United States and worldwide, the rate at which Americans are dying from lung
      cancer is declining. Improving survival can be explained, in large part, by a
      growing understanding of the heterogeneous biology of non-small cell lung cancer
      (NSCLC) as well as recent successes of novel therapeutic strategies more
      effective and tolerable than platinum-based chemotherapy. We now recognize
      distinct subtypes of NSCLC, defined by molecular profiling and
      immunohistochemistry, with different treatment algorithms, including targeted
      small molecular inhibitors and immunotherapy for each. Both biomarker selection
      and preferred frontline strategies continue to evolve rapidly, making it
      difficult for many practitioners to keep up. In this review, we will first
      describe the recommended initial workup for a patient with advanced or metastatic
      NSCLC in 2018; next, we present an algorithm to aid oncologists in the selection
      of the most appropriate therapy for treatment-naive patients with NSCLC, and
      finally, we offer a look into future treatment options through a discussion of
      ongoing clinical trials.

PMID- 30231363
TI  - Implementing Precision Medicine Programs and Clinical Trials in the Community
      Based Oncology Practice: Barriers and Best Practices.
AB  - There has been a rapid uptick in the pace of oncology precision medicine
      advancements over the past several decades as a result of increasingly
      sophisticated technology and the ability to study more patients through
      innovative trial designs. As more precision oncology approaches are developed,
      the need for precision medicine trials is increasing in the community setting,
      where most patients with cancer are treated. However, community-based practices,
      as well as some academic centers, may face unique barriers to implementing
      precision medicine programs and trials within their communities. Such challenges
      include understanding the tissue needs of molecular tests (e.g., tumor, blood),
      identifying which molecular tests are best used and when tissue should be tested,
      interpreting the test results and determining actionability, understanding the
      role of genetic counseling and/or follow-up testing, determining clinical trial
      eligibility, and assessing patient attitudes and financial concerns. The purpose
      of this article is to provide guidance to community-based oncology practices
      currently conducting clinical trials who want to expand their research program to
      include precision medicine trials. Here, we describe the core components of
      precision medicine programs and offer best practices for successful
      implementation of precision medicine trials in community-based practices.

PMID- 30231364
TI  - Cost, Value, and Financial Hardship in Cancer Care: Implications for Pediatric
      Oncology.
AB  - Cancer care in the United States faces a perfect storm: an aging population and
      expected increased cancer incidence, growing numbers of cancer survivors with
      ongoing care needs, and continued scientific advancements, offering extraordinary
      promise at extraordinary cost. How, then, do we as pediatric oncologists engage
      in the dialogue about cancer cost considerations? The purpose of this article and
      its accompanying session presented at the 2018 ASCO Annual Meeting is to
      introduce concepts of cost, value, and financial hardship. In the first section,
      we will provide an overview of principles of health economics, including
      components of cost, time horizon consideration, discounting, and methods to
      calculate incremental cost-effectiveness among therapeutic approaches. We will
      then introduce the value framework being debated in adult oncology and offer
      potential opportunities for its application in pediatric oncology. In the second
      section, we will describe the integration of the cost-effectiveness paradigm in
      an ongoing pediatric clinical trial, including design and analytic
      considerations. In the third section, we will shift away from cost to the health
      care system to cost to the patient, which is also termed "financial toxicity" or
      "financial hardship," focusing on the ongoing burden of cost on survivors of
      childhood cancer. Our goal is to provide our readers with the vocabulary and
      understanding of this complex and often thorny debate so that they can be active
      participants and informed advocates for their patients.

PMID- 30231365
TI  - National Cancer Institute Programmatic Collaboration for Investigational
      Radiopharmaceuticals.
AB  - Radiopharmaceutical therapies have provided an attractive therapeutic approach
      since the introduction of 131I to treat thyroid cancer. New insights in cancer
      biology and radiochemistry have brought radiopharmaceuticals to the leading edge
      of oncology clinical research. National Cancer Institute (NCI) programs watch for
      new radiopharmaceutical breakthroughs that should be used to treat patients with
      unmet therapeutic needs. Such efforts occur through leveraged partnerships
      between NCI's Cancer Therapy Evaluation Program and its Radiation Research
      Program. If groundbreaking discoveries are made, NCI pulls together clinician
      scientists to design novel radiopharmaceutical phase I and II monotherapy or
      combination trials. The specific infrastructure needs, such as
      radiopharmaceutical dosimetry and treatment planning, demand new programmatic
      workflow and regulatory oversight. This article discusses a modern approach to
      the development of radiopharmaceutical therapies in the era of personalized
      medicine.

PMID- 30231366
TI  - Value and Cost of Myeloma Therapy-We Can Afford It.
AB  - A national conversation regarding the price and affordability of drugs exists,
      where concern for value and benefits of medications is challenged by the
      increasing price of both injectable and oral medications, including the cost of
      care of myeloma. At the same time, we have seen unprecedented improvements in the
      overall survival of patients with myeloma, mostly because of the availability of
      these new drugs. Here, we present data to assert that these medications and
      associated expenses are of direct benefit to patients and society. The
      entrepreneurial reward for drug development in the United States has fueled
      vigorous drug development efforts that have culminated in the approval of 11 new
      drugs for the treatment of myeloma by the U.S. Food and Drug Administration (FDA)
      since 1999. These patented drugs are available to patients in the United States
      usually at a higher price than in the rest of the world. Nevertheless, the
      majority of patients, via direct copay assistance or through indirect support via
      third parties, have access to these drugs irrespective of their socioeconomic
      status. One of the major regulatory hurdles that prevents access to these drugs
      is the legal impossibility that pharmaceutical companies have in directly
      supporting copay assistance for patients with government-funded health care.
      Moreover, assessments of value should include formal pharmacoeconomic analyses
      performed by experts. Interference with market forces and coercive action, such
      as price controls, or exercising eminent domain in the quest for cheaper
      medications will stymie innovation and rob us of the cures of the future.

PMID- 30231367
TI  - Immune Checkpoint Inhibitors in the Management of Lung Cancer.
AB  - Immune checkpoint inhibitors, specifically PD-1-directed agents, have changed the
      treatment paradigm of non-small cell lung cancer (NSCLC) and are being actively
      evaluated in patients with small cell lung cancer. After initial studies
      demonstrated survival advantage with these agents in patients with recurrent
      NSCLC, these agents now have demonstrated survival advantage in some patients
      with early-stage NSCLC. Further evaluation of these agents in combination with
      chemotherapy regimens and other checkpoint inhibitors is ongoing. Recent data
      suggest that addition of these agents to chemotherapy may improve survival
      compared with chemotherapy alone. Promising results have also been observed in
      patients with recurrent small cell lung cancer. Ongoing studies will define the
      role of these agents in the management of patients with small cell lung cancer.
      Tumor PD-L1 assessment has become standard of care since use of frontline
      pembrolizumab in patients with advanced NSCLC is based on tumor PD-L1 expression.
      Other biomarkers are being actively evaluated to identify the patients most
      likely to benefit from these agents. Unique adverse effects are observed with the
      use of immune checkpoint inhibitors. Knowledge of the adverse effects and their
      management is crucial in treating patients with lung cancer using immune
      checkpoint inhibitors.

PMID- 30231368
TI  - Risk Stratification and Targets in Multiple Myeloma: From Genomics to the
      Bedside.
AB  - In the past 15 years, significant improvements in overall survival have been
      observed in multiple myeloma (MM), mainly due to the availability of novel drugs
      with variable mechanisms of action. However, these improvements do not benefit
      all patients, and some of them, defined as high risk, still display short
      survival. The most important risk factors are the genetic abnormalities present
      in the malignant plasma cells. The most important high-risk features are the
      del(17p), the del(1p32), the t(4;14), and 1q gains. Assessing these markers is
      mandatory at diagnosis and at least at first relapse, since it has been clearly
      shown that the lenalidomide-dexamethasone combination is not efficient in these
      high-risk patients. In contrast, a triplet combination adding a proteasome
      inhibitor or a monoclonal antibody to the lenalidomide-dexamethasone backbone
      clearly improves the survival. Another way to improve the outcome would be to
      specifically target genetic abnormalities with specific inhibitors. The
      sequencing of more than 1,000 MM exomes revealed again a huge heterogeneity. The
      most frequent mutations involve the KRAS and NRAS genes (20%-25% each). However,
      to date, no good RAS-inhibitors are clinically available, preventing targeted
      therapy. The only drugable target is the V600E BRAF mutation. Unfortunately, this
      specific mutation is present in only 3% of the patients. Finally, it has been
      recently reported a specific efficiency of the BCL2-inhibitor venetoclax in
      patients with the t(11;14) translocation, which is found in 20% of the patients.

PMID- 30231369
TI  - Art and Challenges of Precision Medicine: Interpreting and Integrating Genomic
      Data Into Clinical Practice.
AB  - Precision medicine is at the forefront of innovation in cancer care. With the
      development of technologies to rapidly sequence DNA from tumors, cell-free DNA,
      proteins, and even metabolites coupled with the rapid decline in the cost of
      genomic sequencing, there has been an exponential increase in the amount of data
      generated for each patient diagnosed with cancer. The ability to harness this
      explosion of data will be critical to improving treatments for patients.
      Precision medicine lends itself to big data or "informatics" approaches and is
      focused on storing, accessing, sharing, and studying these data while taking
      necessary precautions to protect patients' privacy. Major cancer care
      stakeholders have developed a variety of systems to incorporate precision
      medicine technologies into patient care as soon as possible and also to provide
      the ability to store and analyze the omics and clinical data aggregately in the
      future. Scaling these precision medicine programs within the confines of health
      care system silos is challenging, and research consortiums are being formed to
      overcome these limitations. Incorporating and interpreting the results of
      precision medicine sequencing is complex and rapidly changing, necessitating
      reliance on a group of experts. This is often performed at molecular tumor boards
      at large academic and research institutions with available in-house expertise,
      but alternative models clinical decision support software or of virtual tumor
      boards potentially expand these advances to almost any patient, regardless of
      site of care. The promises of precision medicine will be more quickly realized by
      expanding collaborations to rapidly process and interpret the growing volumes of
      omics data.

PMID- 30231370
TI  - Practice-Changing Developments in Stage III Melanoma: Surgery, Adjuvant Targeted
      Therapy, and Immunotherapy.
AB  - In this article, we will focus on the practice-changing developments for stage
      III melanoma, from the use of the sentinel node (SN) biopsy to complete lymph
      node dissection (CLND) and upcoming adjuvant therapies. MSLT-1 (Multicenter
      Selective Lymphadenectomy Trial-1) was the first and only prospective randomized
      controlled trial to examine whether the SN biopsy has any notable melanoma
      specific survival benefit (primary endpoint). MSLT-1 randomly assigned 2,001
      patients to undergo either wide local excision (WLE) and an SN biopsy or WLE and
      nodal observation. Two prospective randomized controlled trials have examined the
      potential benefit for immediate CLND versus delayed CLND after sequential
      observation. Both the DECOG-SLT and MSLT-2 trials failed to demonstrate a notable
      benefit for immediate CLND; therefore, sequential follow-up with ultrasonography
      and a delayed CLND in the case of relapse should be considered the new standard
      of care. The CheckMate 238 study demonstrated a notable benefit for adjuvant
      nivolumab in terms of 18-month relapse-free survival (RFS) rates compared with
      high-dose adjuvant ipilimumab. Single-agent adjuvant BRAF inhibition has been
      examined and failed to improve RFS. However, the COMBI-AD study did demonstrate a
      substantial benefit for combination BRAF and MEK inhibition for patients with
      BRAF-mutated resected stage IIIA to IIIC melanoma.

PMID- 30231371
TI  - Emerging Strategies in Systemic Therapy for the Treatment of Melanoma.
AB  - Recent years have seen major improvements in survival of patients with advanced
      melanoma with the advent of various novel systemic immunotherapies and targeted
      therapies. As our understanding of these agents and their various mechanisms of
      action improves, even more impressive outcomes are being achieved through use of
      various combination strategies, including the combining of different
      immunotherapies with one another as well as with other modalities. However,
      despite the improved outcomes that have been achieved in advanced melanoma,
      responses to treatment are heterogeneous and may not always be durable.
      Additional advances in therapy are required, and several emerging strategies are
      a focus of interest. These include the investigation of several new immunotherapy
      and/or targeted therapy combinations, such as checkpoint inhibitors (anti-PD
      1/anti-CTLA-4) with other immunotherapies (e.g., indoleamine 2,3 dioxygenase
      [IDO] inhibitors, antilymphocyte activation 3 [anti-LAG-3], histone deacetylase
      [HDAC] inhibitors, Toll-like receptor 9 [TLR-9] agonists, antiglucocorticoid
      induced tumor necrosis factor receptor [anti-GITR], pegylated interleukin-2 [IL
      2]), combined targeted therapies (e.g., MEK and CDK4/6 coinhibition), and
      combined immunotherapy and targeted therapy (e.g., the triplet combination of
      BRAF/MEK inhibition with anti-PD-1s). The identification of novel therapeutic
      targets in the MAP kinase pathway also offers opportunities to improve outcomes
      by overcoming de novo and acquired resistance to BRAF/MEK inhibition (e.g., the
      development of ERK inhibitors). In addition, adoptive cell transfer, the infusion
      of large numbers of activated autologous lymphocytes, may have a potential role
      in patients whose disease has progressed after immunotherapy. Taken together,
      these new approaches offer further potential to increase systemic treatment
      options and improve long-term outcomes for patients with advanced melanoma.

PMID- 30231372
TI  - Cognitive Changes in Cancer Survivors.
AB  - Advances in cancer treatments have led to substantially improved survival for
      patients with cancer. However, many patients experience changes in cognition as a
      side effect of both cancer and cancer treatment. This occurs with both central
      nervous system (CNS) tumors and non-CNS tumors and in both children and adults.
      Studies of patients with non-CNS cancer have shown that cancer-related cognitive
      impairment (CRCI), which can include changes in memory, executive function,
      attention, and processing speed, occurs in up to 30% of patients prior to any
      treatment and in up to 75% of patients during treatment. A subset of patients
      with non-CNS and CNS cancer appear to be at higher risk for CRCI, so much
      research has gone into identifying who is vulnerable. Risk factors for CRCI in
      adults include cognitive reserve, age, genetic factors, and ethnicity; risk
      factors for children include genetic factors, female sex, younger age at
      diagnosis, chemotherapy dose, and both dose and field size for radiation.
      Although the field has made substantial strides in understanding and treating
      CRCI, more research is still needed to improve outcomes for both pediatric and
      adult cancer survivors.

PMID- 30231373
TI  - CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update.
AB  - Cellular therapies are a rapidly evolving approach to myeloma treatment, which
      bring a unique mechanism of action with the potential to overcome drug resistance
      and induce long-term remissions. Two primary approaches are being studied: non
      gene-modified strategies, which rely on the endogenous anti-myeloma T-cell
      repertoire, and gene-modified strategies, which introduce a new T-cell receptor
      (TCR) or a chimeric antigen receptor (CAR) to confer novel antigen specificity.
      CAR T cells show the greatest activity to date. Multiple antigen targets,
      including B-cell maturation antigen (BCMA), CD19, CD38, CD138, and SLAMF7, are
      being explored for myeloma, and BCMA has emerged as the most promising.
      Preliminary data from four phase I studies of BCMA CAR T cells, each using a
      different CAR construct, that involved 90 evaluable patients with
      relapsed/refractory disease have been reported. These data show response rates of
      60% to 100%, including minimal residual disease (MRD)-negative complete
      remissions, at effective doses (> 108 CAR-positive cells) after lymphodepleting
      conditioning. Response durability has been more variable, likely related to
      differences in CAR T-cell products, lymphodepleting regimens, patient selection
      criteria, and/or underlying biology/prognostic factors. In the two most recent
      studies, however, most patients remained progression free with median follow-up
      time of 6 to 10 months; some ongoing remissions lasted more than 1 year.
      Toxicities are similar to those from CD19 CAR T cells and include cytokine
      release syndrome and neurotoxicity that is reversible but can be severe. Multiple
      BCMA CAR T-cell studies are ongoing. Future directions include combinations with
      immunomodulatory drugs, checkpoint inhibitors, or other CAR T cells, as well as
      use of gene-edited cellular products to enhance the safety and efficacy of this
      approach.

PMID- 30231374
TI  - Integrating Genomics Into Neuro-Oncology Clinical Trials and Practice.
AB  - Important advances in our understanding of the molecular biology of brain tumors
      have resulted in a rapid evolution in the taxonomy of central nervous system
      (CNS) tumors, which culminated in the revised 2016 World Health Organization
      classification of CNS tumors that incorporates an integrated molecular/histologic
      diagnostic approach. Our expanding understanding of brain tumor genomics and
      molecular evolution during the disease course has started to impact clinical
      management. Furthermore, incorporation of genomic information in ongoing and
      planned neuro-oncology clinical trials is expected to lead to improved outcomes
      and result in personalized treatment options for patients with CNS malignancies.

PMID- 30231375
TI  - Personalized Management of Advanced Kidney Cancer.
AB  - The treatment of renal cell carcinoma represents one of the great success stories
      in translational cancer research, with the development of novel therapies
      targeting key oncogenic pathways. These include drugs that target the VEGF and
      mTOR pathways, as well as novel immuno-oncology agents. Despite the therapeutic
      advancements, there is a paucity of well-validated prognostic and predictive
      biomarkers in advanced kidney cancer. With a number of highly effective therapies
      available across multiple lines, it will become increasingly important to develop
      a more tailored approach to treatment selection. Prognostic clinical models, such
      the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)
      model, are routinely used for prognostication in clinical practice. The IMDC
      model has demonstrated a predictive capability in the context of these treatments
      including immune checkpoint inhibition. A number of promising molecular markers
      and gene expression signatures are being explored as prognostic and predictive
      biomarkers, but none are ready to be widely used for treatment selection. In this
      review, we will explore the current landscape of personalized care in metastatic
      renal cell carcinoma. This will include a focus on both prognostic and predictive
      factors as well as clinical applications of biology in kidney cancer.

PMID- 30231376
TI  - Caring for Colleagues and Loved Ones With Cancer.
AB  - Throughout the arc of a career in medicine, physicians are universally faced with
      the difficult decision of when to provide care for a colleague and when to refer
      to another physician. Gauging the magnitude of your relationship, both
      professionally and personally, and then weighing how to add the roles of
      physician and patient to your preexisting relationship is complex. We review and
      discuss care of family and colleagues, address ethical boundaries both firm and
      flexible, and explore the emotional weight of those relationships.

PMID- 30231377
TI  - Communicating the Financial Burden of Treatment With Patients.
AB  - In recent years, high health care costs and the financial burden of cancer care
      have received increased attention. In response to the financial burden of cancer
      care, patients may jeopardize their health outcomes by not properly adhering to
      prescribed therapies or even forgoing and delaying care in an effort to defray
      costs. In addition, the financial burden experienced by patients with cancer may
      negatively impact clinical outcomes, such as quality of life, physical and
      psychological symptoms, and potentially, even survival. Notably, in the current
      era of targeted treatment and immunotherapies for patients with cancer, the
      rising costs of cancer continue to remain at the forefront of patient concerns.
      Therefore, a critical need exists to determine how best to assist patients with
      the cost burden of cancer diagnosis and treatment.

PMID- 30231378
TI  - Tumor Response Assessment for Precision Cancer Therapy: Response Evaluation
      Criteria in Solid Tumors and Beyond.
AB  - Objective assessment of tumor responses and treatment results has been the basis
      for the advancement of cancer therapies, and imaging plays a key role to provide
      a "common language" to describe the results of cancer treatment. Although
      Response Evaluation Criteria in Solid Tumors (RECIST) has been the most widely
      accepted method for assessing tumor response in the past decades, the limitations
      of RECIST have increasingly becoming recognized, especially with the recent
      advances of precision-medicine approaches to cancer. This article reviews the
      current concept of tumor response evaluations based on RECIST, describes the
      limitations of RECIST, and proposes strategies to overcome the limitations. The
      article emphasizes specific limitations in the setting of precision cancer
      therapy and cancer immunotherapy and discusses the important insights provided by
      the cutting-edge investigations in the emerging fields.

PMID- 30231379
TI  - The Winds of Change: Emerging Therapeutics in Prostate Cancer.
AB  - The last decade has seen substantial advances in androgen receptor targeting in
      prostate cancer. In addition, advances have been made in immunotherapy and
      radiopharmaceutical-based therapy, although their optimal use in the clinic
      remains unclear. Recent understanding of the relevance and actionability of DNA
      damage repair mutations in a considerable minority of patients with prostate
      cancer is likely to open up a new frontier in prostate cancer therapeutics. As
      androgen receptor-directed therapy moves earlier in the disease process for
      prostate cancer, advances in these nonandrogen receptor-based therapeutics may
      take on greater significance in the years to come.

PMID- 30231380
TI  - Patterns of Response and Progression to Immunotherapy.
AB  - Patterns of response and progression to immunotherapy may differ from those
      observed with drugs such as chemotherapy and molecularly targeted agents.
      Specifically, some patients experience a response after progression that is
      retrospectively named pseudoprogression. This phenomenon of pseudoprogression,
      first reported in patients with melanoma who were treated with ipilimumab, has
      led to the development of immune-specific related response criteria, such as irRC
      (immune-related response criteria), irRECIST (immune-related RECIST), and iRECIST
      (immunotherapy RECIST) that allow continued treatment beyond progression.
      However, the rate of pseudoprogression has never exceeded 10% of patients across
      tumor types. Conversely, rapid progressions after immunotherapy, called
      hyperprogressions, were reported by three different teams in 9% to 29% of
      patients treated with immunotherapy. Because of the absence of control arms in
      these studies, it remains to be determined whether these rapid progressions
      reflect a detrimental effect of immunotherapy in these patients. Finally,
      preliminary data suggest that immunotherapy might also affect response to
      subsequent standard therapies. In total, given the rarity of pseudoprogressions
      across tumor types and the recent description of hyperprogressions, classic
      RECIST remains a reasonable and rational method to assess response to
      immunotherapy. Continuation of treatment beyond progression should be proposed
      only in carefully selected patients whose clinical conditions have improved and
      who have not experienced severe toxicities. Although there is an urgent need to
      identify predictive biomarkers of efficacy to immunotherapy, there is an equally
      urgent need to identify predictive factors of progression or possibly
      hyperprogression.

PMID- 30231381
TI  - Implementation of Patient-Reported Outcomes in Routine Medical Care.
AB  - There is increasing interest to integrate collection of patient-reported outcomes
      (PROs) in routine practice to enhance clinical care. Multiple studies show that
      systematic monitoring of patients using PROs improves patient-clinician
      communication, clinician awareness of symptoms, symptom management, patient
      satisfaction, quality of life, and overall survival. The general approach
      includes a brief electronic survey, administered via the Web or an app or an
      automated telephone system, with alerts to clinicians for concerning or worsening
      issues. Patients have generally been asked to self-report on a regular basis
      (remotely between visits and/or at visits), with reminders prompting patients to
      self-report that are sent via email, text, or automated phone message. More
      recently, care management pathways for patients and clinicians have been
      triggered by PRO system alerts. PRO systems may be free-standing, integrated into
      electronic health record systems or patient portals, or native functionality of
      an electronic health record. Despite potential benefits, there are challenges
      with integrating PROs into practice for monitoring patient status, as there are
      with any modifications to existing clinical processes. These challenges range
      from administrative to technical to workflow. A session at the 2018 ASCO Annual
      Meeting was dedicated to the implementation of PROs in clinical practice. The
      session focused on practical examples of PRO implementations, with honest
      reflections on barriers and strategies that may be generalizable to other systems
      looking to implement PROs. Panelists for that session are the authors of this
      paper, which describes their respective experiences implementing PROs in practice
      settings.

PMID- 30231382
TI  - Sequencing Therapy for Genetically Defined Subgroups of Non-Small Cell Lung
      Cancer.
AB  - The practice of precision medicine for patients with metastatic non-small cell
      lung cancer (NSCLC), particularly those patients with adenocarcinoma histology
      (the predominant subtype of NSCLC), has become the accepted standard of care
      worldwide. Implementation of prospective tumor molecular profiling and rational
      therapeutic decision-making based on the presence of recurrently detected
      oncogenic "driver" alterations in the tumor genome has revolutionized the way
      that lung cancer is diagnosed and treated in the clinic. Over the past two
      decades, there has been a deluge of therapeutically actionable driver alterations
      and accompanying small molecule inhibitors to target these drivers. Herein, we
      synthesize a large and rapidly growing body of literature regarding therapeutic
      inhibition of driver mutations. We focus on established targets, including EGFR,
      anaplastic lymphoma kinase (ALK), ROS1, BRAF, RET, MET, HER2, and neurotrophic
      tyrosine kinase receptor (NTRK), with a particular emphasis on the sequencing of
      small molecule inhibitors in these genetically defined cohorts of patients with
      lung cancer.

PMID- 30231383
TI  - Neoadjuvant Chemotherapy, Concurrent Chemoradiation, and Adjuvant Chemotherapy
      for High-Risk Extremity Soft Tissue Sarcoma.
AB  - Standard treatment of large intermediate- and high-grade extremity soft tissue
      sarcoma (ESTS) typically includes wide excision and radiation therapy. Many
      patients do well with this approach, but for those with unfavorable features,
      risk for distant recurrence and, ultimately, mortality can exceed 50%.
      Unfortunately, universally accepted data elucidating effective treatments to
      prevent recurrences and improve survival for such high-risk patients are lacking.
      Accordingly, opinions about the appropriate role of systemic therapy for patients
      with high-risk localized ESTS vary. This article reviews the current literature
      pertaining to neoadjuvant chemotherapy, concurrent chemoradiation, and adjuvant
      chemotherapy for high-risk ESTS. All of these approaches are feasible and
      reasonable to consider. Ultimately, the decision to incorporate chemotherapy into
      the treatment regimen is best reached by discussion among an experienced
      multidisciplinary sarcoma team and should be tailored to the individual patient
      risk profile.

PMID- 30231384
TI  - "How Much Time Do I Have?": Communicating Prognosis in the Era of Exceptional
      Responders.
AB  - Prognostication is the science by which clinicians estimate a patient's expected
      outcome. A robust literature shows that many patients with advanced cancer have
      inaccurate perceptions of their prognosis, thus raising questions about whether
      patients are truly making informed decisions. Clinicians' ability to communicate
      prognostic information is further complicated today by the availability of novel,
      efficacious immunotherapies and genome-guided treatments. Currently, clinicians
      lack tools to predict which patients with advanced disease will achieve an
      exceptional response to these new therapies. This increased prognostic
      uncertainty on the part of clinicians further complicates prognostic
      communication with patients. Evidence also suggests that many oncologists avoid
      or rarely engage in prognosis-related communication and/or lack skills in this
      area. Although communication skills training interventions can have a positive
      impact on complex communication skills for some clinicians, there is no one-size
      fits-all approach to improving patient-clinician communication about prognosis.
      Yet improving patient understanding of prognosis is critical, because patient
      understanding of prognosis is linked with end-of-life care outcomes. Solutions to
      this problem will likely require a combination of interventions beyond
      communication skills training programs, including enhanced use of other cancer
      clinicians, such as oncology nurses and social workers, increased use of
      palliative care specialists, and organizational support to facilitate advance
      care planning.

PMID- 30231385
TI  - Bones in Multiple Myeloma: Imaging and Therapy.
AB  - Bone disease is the most frequent disease-defining clinical feature of multiple
      myeloma (MM), with 90% of patients developing bone lesions over the course of
      their disease. For this reason, imaging plays a major role in the management of
      disease in patients with MM. Although conventional radiography has traditionally
      been the standard of care, its low sensitivity in detecting osteolytic lesions
      has called for more advanced imaging modalities. In this review, we discuss the
      advantages, indications, and applications of whole-body low-dose CT (WBLDCT), 18F
      fluorodeoxyglucose (FDG)-PET/CT, MRI, and other novel imaging modalities in the
      management of disease in patients with plasma cell dyscrasias. We also review the
      state of the art in treatment of MM bone disease (MMBD) and the role of
      bisphosphonates and denosumab, a monoclonal antibody that binds and blocks the
      activity of receptor activator of nuclear factor-kappa B ligand (RANKL), which
      was recently approved by the U.S. Food and Drug Administration for MMBD.

PMID- 30231386
TI  - Multidisciplinary Management of Oligometastatic Soft Tissue Sarcoma.
AB  - Soft tissue sarcomas (STS) encompass a group of rare but heterogeneous diseases.
      Nevertheless, many patients, particularly those with oligometastatic disease can
      benefit from thoughtful multimodality evaluation and treatment regardless of the
      STS subtype. Here, we review surgical, interventional radiology, radiation, and
      chemotherapy approaches to maximize disease palliation and improve survival,
      including occasionally long-term disease-free survival. Surgical resection can
      include lung or other visceral, soft tissue and bone metastases with a goal of
      rendering the patient disease free. Staged resections can be appropriate, and
      serial resection of oligometastatic recurrent disease can be appropriate.
      Retrospective series suggest survival benefit from this approach, although
      selection bias may contribute. Interventional radiology techniques such as
      percutaneous thermal ablation (PTA) and arterial embolization can present
      nonoperative local approaches in patients who are not medically fit for surgery,
      surgery is too morbid, or patients who decline surgery. Similarly, radiation
      therapy can be delivered safely to areas that are inaccessible surgically or
      would result in excessive morbidity. Currently no randomized trials exist
      comparing interventional radiologic approaches or radiation therapy to surgery
      but retrospective reviews show relatively similar magnitude of benefit in terms
      of disease palliation and survival, although it is felt unlikely that these
      procedures will render a patient to long-term disease-free status. Chemotherapy
      has evolved recently with the addition of several new treatment options, briefly
      reviewed here. Importantly, if a patient sustains a good response to chemotherapy
      resulting in true oligometastatic disease, consideration of multimodality local
      therapy approaches can be considered in the appropriate patient.

PMID- 30231387
TI  - Incorporating Genomics Into the Care of Patients With Advanced Breast Cancer.
AB  - Metastatic breast cancer is a very heterogeneous disease. Recent advances in
      genomic sequencing have revealed genetic diversity between patients and across
      distinct subclonal cell populations within the same patient that may evolve
      across metastatic tumor sites and during treatment. With the increasing
      availability of commercial and laboratory-developed tests that can detect genomic
      alterations from patient tumor and blood samples, translating this knowledge into
      improved clinical care remains a challenge. The goals of this review are to
      outline the clinical relevance of tumor genomic heterogeneity and clonal
      evolution, to help clinicians understand how to interpret genomic testing
      reports, and to provide an overview of recurrent genomic alterations that may be
      relevant for clinical trials with investigational drug treatments.

PMID- 30231388
TI  - Metastatic Castration-Sensitive Prostate Cancer: Optimizing Patient Selection and
      Treatment.
AB  - The treatment landscape for metastatic castration-sensitive prostate cancer
      (mCSPC) has rapidly evolved over the past 5 years. Although androgen-deprivation
      therapy (ADT) is still the backbone of treatment, the addition of docetaxel or
      abiraterone acetate has improved outcomes for patients with mCSPC and become
      standard of care. With multiple treatment options available for patients with
      mCSPC, treatment selection to optimize patient outcomes has become increasingly
      difficult. Here, we review the clinical trials involving ADT plus docetaxel or
      abiraterone and provide clinicians with guidelines for treatment. Although
      surgery and/or radiation are standard of care for localized, intermediate- and
      high-risk prostate cancer, these treatments are not routinely used as part of
      initial treatment plans for patients with de novo mCSPC. Recent clinical data are
      challenging that dogma, and we review the literature on the addition of surgery
      and radiation to systemic therapy for mCSPC. Finally, the standard of care for
      oligometastatic prostate cancer (a subset of mCSPC with limited metastases) has
      not been established compared with that for some other cancers. We discuss the
      recent studies on metastasis-directed therapy for treatment of oligometastatic
      prostate cancer.

PMID- 30231389
TI  - Identification, Prioritization, and Treatment of Mutations Identified by Next
      Generation Sequencing.
AB  - Many targeted therapies-and, more recently, immunotherapies-have been approved by
      the U.S. Food and Drug Administration (FDA) with companion diagnostic tests. Next
      generation sequencing (NGS) platforms are now approved to screen for many of
      these abnormalities, and they are increasingly being applied to guide therapeutic
      decision-making outside of these intended uses. The results provided by NGS
      testing can vary significantly based on the exact test performed and the analysis
      of the sequencing data. Given the complexities associated with interpreting NGS
      test results and acting on them, academic and community molecular tumor boards
      have been developed to provide multidisciplinary expertise for this endeavor. NGS
      test results may identify FDA-approved therapies, guide clinical trial
      recommendations, or prompt consideration of expanded access to investigational
      agents or off-label use of therapies approved for other indications. Many
      clinical trials now include NGS testing to assign treatments to patients based on
      the molecular profiles of their tumors. Although NGS testing may eventually help
      realize the development of individualized treatment regimens based on
      combinations of targeted therapies, the use of unproven and nonapproved
      combinations can be toxic and expensive. Given the increasing reliance on genetic
      biomarkers to guide therapeutic recommendations for FDA-approved therapies or
      enrollment into clinical trials, NGS will remain an integral part of the evolving
      medical oncology practice.

PMID- 30231390
TI  - Recent Advances in Lynch Syndrome: Diagnosis, Treatment, and Cancer Prevention.
AB  - Identification of individuals with inherited predispositions to cancer, including
      Lynch syndrome, can help prevent cancer and cancer-related death by allowing for
      the uptake of specific cancer prevention and screening as well as the use of
      therapies directed toward the underlying neoplastic process for individuals with
      advanced cancer. In the 25 years since the discovery of microsatellite
      instability (MSI) and the first recognition of germline mismatch repair (MMR)
      gene variants as the etiologic basis of Lynch syndrome, there has been tremendous
      progress in the understanding of the spectrum of cancer risk associated with
      Lynch syndrome as well as in cancer prevention and risk-reduction strategies. The
      past few years, in particular, have brought transformative changes in the
      treatment of Lynch syndrome-associated cancers with immune checkpoint inhibitors.
      In parallel, advances in next-generation sequencing (NGS) technologies now allow
      rapid and scalable somatic and germline sequencing that promises to help identify
      Lynch syndrome in individuals who otherwise lack classic phenotypes. Last, real
      progress is being made to understand more sophisticated methods of precision
      cancer prevention, including chemotherapeutic prevention agents (e.g., aspirin)
      and strategies that leverage the immune system to facilitate primary cancer
      prevention in otherwise-healthy Lynch syndrome carriers.

PMID- 30231391
TI  - Best Practices in Oncology Distress Management: Beyond the Screen.
AB  - The field of psychosocial oncology is a young discipline with a rapidly expanding
      evidence base. Over the past few decades, several lines of research have
      established that psychosocial problems, such as anxiety, depression, post
      traumatic stress, fatigue, sexual dysfunction, and cognitive complaints, are
      common and consequential in patients with cancer. The word "distress" was chosen
      deliberately to capture a broad concept; consequently, distress screening is
      meant to function as an initial step in the more targeted evaluation of the
      source(s) of the patient's distress. In 2015, the American College of Surgeons'
      Commission on Cancer mandated psychosocial distress screening as part of their
      accreditation process. Similar screening requirements are in place
      internationally, including in Canada, where screening for distress is endorsed as
      the sixth vital sign and a standard of care that must be met by any Canadian
      health care organization providing cancer services that seeks to be accredited.
      Over the past few years, cancer centers around the world have been exploring
      optimum ways to implement and evaluate distress screening initiatives. This paper
      presents three approaches to distress screening implementation: (1) a model that
      incorporates the importance of shared values, perceived benefits, and relevant
      outcomes in the implementation of distress management protocols; (2) a Canadian
      knowledge translation application to distress screening, including triage
      considerations and interventions; and (3) a novel approach to distress management
      via the use of a mobile application to manage post-traumatic stress symptoms. In
      closing, future opportunities and challenges associated with the emergence of
      technology will be discussed.

PMID- 30231392
TI  - Cancer of Unknown Primary Site: New Treatment Paradigms in the Era of Precision
      Medicine.

PMID- 30231393
TI  - Approaches to Chronic Lymphocytic Leukemia Therapy in the Era of New Agents: The
      Conundrum of Many Options.
AB  - Three small molecule inhibitors have been approved for the treatment of chronic
      lymphocytic leukemia (CLL) in the last 4 years. Ibrutinib, idelalisib, and
      venetoclax are oral agents with excellent efficacy and different toxicity
      profiles. Issues discussed herein include the current role for chemoimmunotherapy
      in CLL, the use of oral inhibitors in older patients, and the sequencing of these
      molecules in daily practice.

PMID- 30231394
TI  - From Burnout to Resilience: An Update for Oncologists.
AB  - Physician burnout remains a highly complex and topical issue. The negative impact
      of burnout on physicians, patients, and institutions has become increasingly
      apparent. Globally, a multitude of professional bodies and organizational leaders
      are giving this important subject much-deserved attention. In this review, we
      provide a summary of the latest evidence, with a focus on solutions and future
      strategies, while incorporating our own perspectives as practicing oncologists.

PMID- 30231395
TI  - Evolution of Targeted Therapy in Breast Cancer: Where Precision Medicine Began.
AB  - As we consider best practices and approaches to targeted therapy in the clinic
      and in terms of trial design, breast cancer can serve as a useful model for other
      disease types, because estrogen receptor-positive and HER2-positive breast cancer
      have been known entities for several decades. In this review, we provide a
      history of the development of anti-estrogen therapy and anti-HER2-directed
      therapy and we discuss our growing understanding of resistance to targeted
      therapy as seen through this lens. We highlight some of the recent breakthroughs
      that have enhanced our understanding of resistance to endocrine and anti-HER2
      therapy, and we discuss some of the ongoing research in the field.

PMID- 30231396
TI  - Predicting and Preventing Anthracycline-Related Cardiotoxicity.
AB  - Anthracyclines (doxorubicin, daunorubicin, epirubicin, and idarubicin) are among
      the most potent chemotherapeutic agents and have truly revolutionized the
      management of childhood cancer. They form the backbone of chemotherapy regimens
      used to treat childhood acute lymphoblastic leukemia, acute myeloid leukemia,
      Hodgkin lymphoma, Ewing sarcoma, osteosarcoma, and neuroblastoma. More than 50%
      of children with cancer are treated with anthracyclines. The clinical utility of
      anthracyclines is compromised by dose-dependent cardiotoxicity, manifesting
      initially as asymptomatic cardiac dysfunction and evolving irreversibly to
      congestive heart failure. Childhood cancer survivors are at a five- to 15-fold
      increased risk for congestive heart failure compared with the general population.
      Once diagnosed with congestive heart failure, the 5-year survival rate is less
      than 50%. Prediction models have been developed for childhood cancer survivors
      (i.e., after exposure to anthracyclines) to identify those at increased risk for
      cardiotoxicity. Studies are currently under way to test risk-reducing strategies.
      There remains a critical need to identify patients with childhood cancer at
      diagnosis (i.e., prior to anthracycline exposure) such that noncardiotoxic
      therapies can be contemplated.

PMID- 30231397
TI  - Immunotherapy in Older Adults With Advanced Cancers: Implications for Clinical
      Decision-Making and Future Research.
AB  - Immunotherapy has expanded the therapeutic landscape for advanced cancers,
      including solid tumors and lymphomas. For many patients with cancer, these agents
      have been shown to have substantial efficacy and favorable toxicity compared with
      cytotoxic agents, particularly in the second-line setting. With the advent of
      anti-PD-1 and anti-PD-L1 checkpoint inhibitors, combination immunotherapy- and
      chemoimmunotherapy-based strategies have emerged as promising novel regimens to
      improve cancer-related outcomes. Older adults age 65 or older represent the
      growing majority of patients diagnosed with cancer. However, older adults are
      under-represented in clinical trials in general, as well as in the landmark
      studies that led to approval of these immunotherapy agents. Because of increasing
      age and attendant multimorbidity and impaired functional status, many of these
      patients seen in the community-based oncology practices would not have been
      considered eligible for such studies. Thus, the results of these studies are
      difficult to generalize to a broader patient population with these competing
      risks. Furthermore, robust evaluation of toxicities, effect on quality of life
      and functional status, and aging-related (i.e., immunosenescence) and
      immunotherapy-related changes affecting the immune system remain underexplored
      research areas for older adults. This review examines the role of immunotherapy
      and its unique issues, specifically in older adults with lung cancer, bladder
      cancer, and lymphomas.

PMID- 30231398
TI  - What Will We Expect From Novel Therapies to Esophageal and Gastric Malignancies?
AB  - Esophageal cancer and gastric cancer are aggressive diseases for which treatment
      approaches are facing a new era. Some molecular pathways, such as VEGF, EGFR,
      fibroblast growth factor receptor, PIK3CA, and PARP-1, have been studied, and
      novel targeted drugs are presumed to be developed in the near future. From The
      Cancer Genome Atlas report, 80% of Epstein-Barr virus tumors and 42% of tumors
      with microsatellite instability have PIK3CA mutations, suggesting that this
      pathway could be reevaluated as a possible target for new systemic treatment of
      gastric cancer. Notably, higher PARP-1 expression can be found in gastric cancer,
      which might be related to more advanced disease and worse prognosis. In addition,
      PD-L1 expression, high microsatellite instability, and mismatch repair deficiency
      can be found in gastric cancer, thus suggesting that immunotherapy may also play
      a role in those patients. We discuss trends related to the potential of novel
      therapies for patients with esophageal and gastric cancers in the near future.

PMID- 30231399
TI  - New and Important Changes in the TNM Staging System for Breast Cancer.
AB  - Expanded understanding of biologic factors that modulate the clinical course of
      malignant disease have led to the gradual integration of biomarkers into staging
      classifications. The American Joint Committee on Cancer (AJCC) TNM staging system
      is universally used and has largely displaced other staging classifications for
      most, although not all, cancers. Many of the chapters of the eighth edition of
      the AJCC TNM staging system integrated biomarkers with anatomic definitions. The
      Breast Chapter added estrogen receptor (ER) and progesterone receptor (PR)
      expression, HER2 expression, and/or amplification and histologic grade to the
      anatomic assessment of tumor size, regional lymph node involvement, and distant
      metastases (known as TNM). While preserving an anatomic staging system for
      continuity and for regions where modern biomarkers are not always available, the
      eighth edition emphasizes the increased prognostic precision of the clinical
      prognostic stage groups and the pathologic prognostic stage groups. The clinical
      prognostic stage groups are applicable to all patients with primary breast cancer
      before any treatment has been implemented, but require a clinical and imaging
      evaluation as well as a biopsy with grade and available ER, PR, and HER2 results;
      the pathologic prognostic stage groups are applicable to all patients treated
      with complete surgical excision as first treatment and also require a complete
      pathology report, grade, and ER, PR, and HER2. Applying the pathologic prognostic
      stage groups to a large database of patients staged by basic TNM groupings
      changed the stage grouping of almost 40% of patients. Grouping by pathologic
      prognostic stage groups led to a better prognostic distribution of the group and
      more precise individual prognostication.

PMID- 30231400
TI  - Major Changes in Head and Neck Staging for 2018.
AB  - Oncologists should be aware of three major modifications and additions to staging
      head and neck cancer that became effective in 2018. Oral cavity cancers have the
      addition of depth of invasion; oropharyngeal cancers (OPCs) are now distinguished
      by the immunohistochemical stain, p16, into those that are associated with high
      risk human papillomavirus and those that are not; and all sites except
      nasopharyngeal carcinoma and high-risk human papillomavirus OPC will now include
      the important parameter of extranodal extension. The rationale and emerging data
      supporting these changes are discussed in this article and the accompanying oral
      presentation at the 2018 ASCO Annual Meeting.

PMID- 30231401
TI  - Gastrointestinal and Hepatic Toxicities of Checkpoint Inhibitors: Algorithms for
      Management.
AB  - Gastrointestinal toxicities are among the leading causes of immune-related
      adverse effects of checkpoint blockade. These adverse events can be severe enough
      to require interruption or withdrawal of immune checkpoint blockade therapy.
      Patients with immune-related adverse effects require early recognition with an
      evaluation to rule out alternative etiologies and effective management to
      minimize complications. This article reviews the gastrointestinal and hepatic
      toxicities of the antibodies that target immune checkpoints CTLA-4 and PD-1/PD-L1
      and provides an approach to their diagnosis and management.

PMID- 30231402
TI  - No Decision Is Final: Career Planning and Career Transitions.
AB  - Several factors play a role in job selection after completion of a
      hematology/oncology training program, such as a fellows' overall career goals,
      expected income potential, and limitations imposed by visa status, among many
      others. Training programs play an integral role in mentoring trainees in career
      selection. For many, the first job is often not career-long. In addition to
      considerations for a fellow considering a first job out of fellowship, physicians
      will consider a change because of dissatisfaction at one's current position,
      desire for advancement opportunities, or a desire to work in a different sector.
      Other factors include non-occupational issues such as career opportunities for a
      spouse or desire for a different geographic location. Frequent employment changes
      are common with crossover between academia, clinical practice, industry, or
      government service. Possessing the skills needed to recognize one's strengths,
      weaknesses, and goal prioritization can allow for more optimal job selection
      should a career transition into a different discipline occur. Recognizing
      opportunities that present themselves and potentially taking advantage of them
      can lead to professional and personal growth.

PMID- 30231403
TI  - Challenging Cases: Management of Immune-Related Toxicity.
AB  - The approvals of six checkpoint inhibitory antibodies since 2011 have established
      immunotherapy for cancer as a fifth treatment modality after chemotherapy,
      surgery, radiation, and targeted therapy. Long-lasting responses have been
      observed in melanoma, non-small cell lung cancer, renal cell cancer, and head and
      neck cancer, to name a few, and more approvals for these drugs undoubtedly are
      coming in the near future. The application of checkpoint inhibitors has expanded
      well beyond melanoma, and, with wider use, the management of the immune-related
      adverse events (irAEs) that accompany these drugs has received increased
      attention. In this work, several patient cases are presented that highlight how
      to optimally manage these unique toxicities and that illustrate the basic
      principles of care for patients who receive checkpoint inhibition.

PMID- 30231405
TI  - Value and Cost of Myeloma Therapy.
AB  - Major advances have occurred in the treatment of multiple myeloma, including
      several new drugs that typically cost more than $100,000 per year. Although the
      gains in myeloma therapy improve overall survival considerably, they are
      available to only a fraction of the population of patients with myeloma in the
      world because of regulatory barriers and cost. Myeloma is an example of what is
      happening in cancer on a much larger scale. Many of the problems discussed call
      for a wider discussion across all cancers, but they are amplified in myeloma
      because of the need for multidrug regimens that combine three or more expensive
      new drugs for prolonged periods of time. In this article, the reasons for the
      high cost of cancer drugs and possible solutions are examined. The lack of
      correlation of value and price, the remarkable rise in prices of existing old
      medications over time, and the lack of access to lifesaving drugs across various
      countries are also discussed.

PMID- 30231404
TI  - Breast Cancer in Latin America: A Map of the Disease in the Region.
AB  - In the next few decades, breast cancer will become a leading global public health
      problem as it increases disproportionately in low- and middle-income countries.
      Disparities are clear when comparisons are made with rates in Europe and the
      United States, but they also exist between the countries of the region or even
      within the same country in Latin America. Large cities or urban areas have better
      access and resource availability than small towns or remote zones. This article
      presents the status of the disease across 12 years with data obtained through
      three studies performed in 2006, 2010, and 2013 and based on surveys, reviews of
      literature, patient organizations, and public databases. The first study provided
      a general picture of breast cancer control in the region (Latin America); the
      second compared expert perceptions with medical care standards; and the third was
      a review of literature and public databases together with surveys of breast
      cancer experts and patient organizations. We conclude that breast cancer is the
      most frequent cancer and kills more women than any other cancer; we also suggest
      that aging is the principal risk factor, which will drive the incidence to
      epidemic levels as a result of demographic transition in Latin America. The
      economic burden also is large and can be clearly observed: in countries that
      today allocate insufficient resources, women go undiagnosed or uncared for or
      receive treatment with suboptimal therapies, all of which results in high
      morbidity and the associated societal costs. The vast inequities in access to
      health care in countries translates into unequal results in outcomes. National
      cancer control plans are the fundamental building block to an organized
      governance, financing, and delivery of health care for breast cancer.

PMID- 30231406
TI  - Global Health Perspective in Sarcomas and Other Rare Cancers.
AB  - Sarcomas, rare and heterogenous malignancies that comprise less than 1% of all
      cancers, have poor outcomes in the metastatic and refractory setting. Their
      management requires a multidisciplinary approach that consists of medical and
      surgical oncologists, radiation oncologists, and pathologists as well as
      ancillary support. In addition to systemic treatments, most patients will require
      surgical resection and radiation therapy, which mandates the use of the latest
      technologies and specialized expertise. Management guidelines have been developed
      in high-income countries, but their applicability in low-income countries, where
      resources may be limited, remains a challenge. In this article, we propose the
      best possible evidence-based practices specifically for income-constrained
      settings to overcome this challenge. In addition, we review the different methods
      that can be used in low-income countries to access new and expensive treatments,
      which often times carry prohibitive costs for these areas.

PMID- 30231407
TI  - Cardiac Toxicities in the Era of Precision Medicine: Underlying Risk Factors,
      Targeted Therapies, and Cardiac Biomarkers.
AB  - Cancer therapies can cause a variety of cardiac toxicities, including ischemia,
      cardiomyopathy, heart failure, myocarditis, arrhythmias, vascular disease,
      hypertension, and hyperlipidemia. Addressing cardiovascular risk at baseline,
      before initiating therapy, during cancer treatment, and in the survivorship
      period is imperative. It may be useful to risk stratify individuals with
      cardiovascular risk factors using biomarkers or imaging before they receive
      potentially cardiotoxic therapies. Additionally, new guidelines recommend cardiac
      imaging with echocardiography in the survivorship period 6 to 12 months after
      completing cancer therapy for these high-risk individuals. Close collaboration
      between cardiology and oncology in both clinical practice and future research is
      essential.

PMID- 30231408
TI  - What Makes a Pancreatic Cancer Resectable?
AB  - The majority of patients with localized pancreatic cancer who undergo surgery
      with or without adjuvant therapy will develop metastatic disease, suggesting that
      surgery alone is not sufficient for cure and micrometastases are present at the
      time of diagnosis even when not clinically apparent. As such, the field is
      rapidly moving to consensus on treatment sequencing, which emphasizes the early
      delivery of systemic therapy and the application of surgery to the population of
      patients most likely to receive clinical benefit from such large operations
      namely, those with stable or responding disease following systemic therapy and
      often chemoradiation. There remains incomplete consensus about the definition of
      what is operable (both tumor anatomy and patient age/comorbidities) and whether
      the operation should be performed in a high-volume center by more experienced
      surgeons. In this article, we try to provide a comprehensive description of when
      surgery should be performed and what constitutes an operable tumor. Such
      information is critically important for the optimal delivery of stage-specific
      therapy and to allow physicians to provide accurate expectations to all patients
      for treatment outcome. The complex issues of where and by whom such large
      operations should be performed is beyond the scope of this review.

PMID- 30231409
TI  - Incorporating Biology Into Breast Cancer Staging: American Joint Committee on
      Cancer, Eighth Edition, Revisions and Beyond.
AB  - Higher-quality imaging, refined surgical procedures, enhanced pathologic
      evaluation, and improved understanding of the impact of tumor biology on
      treatment and prognosis have necessitated revisions of the AJCC breast cancer
      staging system. The eighth edition includes clinical and pathologic prognostic
      stages that incorporate biologic variables-grade, estrogen and progesterone
      receptor status, HER2 status, and multigene panels-with the anatomic extent of
      disease defined by tumor, node, and metastasis categories. The prognostic staging
      systems facilitate more refined stratification with respect to survival than
      anatomic stage alone. Because the prognostic staging systems are dependent on
      biologic factors, accuracy is dependent on rigorous pathologic evaluation of
      tumors and on administration of treatment dictated by tumor biology. It is
      anticipated that technological advances will facilitate even more refined
      determination of underlying biology within tumors and in the peripheral blood,
      which increasingly is being evaluated as a compartment that reflects the primary
      tumor and sites of distant metastases. Diseases should be staged according to the
      eighth edition staging system to accurately reflect prognosis and to allow
      standardized data collection. Such standardization will facilitate assessment of
      the impact of advances in diagnosis and treatment of patients with breast cancer.

PMID- 30231410
TI  - Role of Germline Genetics in Identifying Survivors at Risk for Adverse Effects of
      Cancer Treatment.
AB  - The growing population of cancer survivors often faces adverse effects of
      treatment, which have a substantial impact on morbidity and mortality. Although
      certain adverse effects are thought to have a significant heritable component,
      much work remains to be done to understand the role of germline genetic factors
      in the development of treatment-related toxicities. In this article, we review
      current understanding of genetic susceptibility to a range of adverse outcomes
      among cancer survivors (e.g., fibrosis, urinary and rectal toxicities,
      ototoxicity, chemotherapy-induced peripheral neuropathy, subsequent
      malignancies). Most previous research has been narrowly focused, investigating
      variation in candidate genes and pathways such as drug metabolism, DNA damage and
      repair, and inflammation. Few of the findings from these earlier candidate gene
      studies have been replicated in independent populations. Advances in
      understanding of the genome, improvements in technology, and reduction in
      laboratory costs have led to recent genome-wide studies, which agnostically
      interrogate common and/or rare variants across the entire genome. Larger cohorts
      of patients with homogeneous treatment exposures and systematic ascertainment of
      well-defined outcomes as well as replication in independent study populations are
      essential aspects of the study design and are increasingly leading to the
      discovery of variants associated with each of the adverse outcomes considered in
      this review. In the long-term, validated germline genetic associations hold
      tremendous promise for more precisely identifying patients at highest risk for
      developing adverse treatment effects, with implications for frontline therapy
      decision-making, personalization of long-term follow-up guidelines, and potential
      identification of targets for prevention or treatment of the toxicity.

PMID- 30231412
TI  - Supporting Caregivers of Patients With Cancer: A Summary of Technology-Mediated
      Interventions and Future Directions.
AB  - This paper aims to review literature published on the support of cancer
      caregivers with health technology. Eighteen articles were reviewed to better
      understand cancer caregiving and categorized into four different themes: (1)
      design guidelines, (2) information facilitation, (3) social support, and (4)
      multicomponent interventions. Analysis of the current articles revealed that
      there are substantial gaps in knowledge regarding a range of health technologies
      that facilitate family caregiver support and its distribution to health
      institutions. Further research is needed in this area, as family caregivers are
      primary providers of essential elements of care to patients. Future studies
      should unpack existing barriers that interfere with the development of health
      technology interventions in cancer care.

PMID- 30231413
TI  - The Role of Statistics in Regulatory Decision Making.
AB  - The number of statistical challenges facing regulators remains high, as does the
      importance of statistical thinking in the regulatory decision-making process.
      Statisticians in the Office of Biostatistics at the US Food and Drug
      Administration review hundreds of new drug and therapeutic biologic applications
      each year and advise sponsors on protocols numbering in the thousands. In
      addition to remaining up to date on the newest statistical methods, statisticians
      are often called upon for innovative approaches to difficult regulatory problems.
      This article presents the author's view of the important role that statisticians
      play in regulatory decision making, beginning with a broad overview of current
      office initiatives, including the development of guidance documents and a recent
      push for open and transparent collaboration with industry on methods development.
      Several recent examples are provided to illustrate the impact that statisticians
      can have on regulatory decisions through the use of strategic quantitative
      thinking. Also discussed are areas where it is believed that innovative
      statistical solutions or greater clarity on existing approaches is still needed.

PMID- 30231414
TI  - Recent Statistical Contributions to Medical Device Development.
AB  - Clinical trials in the development of new medical device products are in many
      ways analogous to clinical trials in the development of new drug or biologic
      products. However, the differences are important and not always intuitive to a
      statistician with only experience supporting development of drug and biologic
      products. In this paper we discuss some of the interesting differences with focus
      on the statistical innovation that is coming out of the medical device area. We
      discuss examples of the differences in clinical trial design and effects of these
      differences on clinical development programs.

PMID- 30231411
TI  - Care After Chemotherapy: Peripheral Neuropathy, Cannabis for Symptom Control, and
      Mindfulness.
AB  - As cancer therapies improve, patients are living longer. With these improvements
      in therapy comes a responsibility to optimize patients' quality of life during
      cancer therapy and beyond. This report reviews three timely and important topics.
      The first section reviews the mechanism underlying chemotherapy-induced
      peripheral neuropathy and evaluates the evidence for interventions to prevent and
      treat peripheral neuropathy. It also provides a framework for approaching the
      diagnosis and management of this common and bothersome side effect. The second
      section addresses the controversial but effective use of cannabinoids for cancer
      and chemotherapy symptoms. Although clinical trials are difficult to conduct
      because of the political and social stigma of this class of drugs, this review
      provides evidence of the efficacy of cannabinoids for treatment of pain and
      nausea. The last section addresses the mind-body connection, with a focus on the
      negative emotions patients with cancer often experience. This section assesses
      the literature regarding mindfulness-based programs to improve cancer-related
      stress. These three topics may appear unrelated, but all address one common goal:
      treating the body and the mind to optimize quality of life during and after
      cancer therapy.

PMID- 30231415
TI  - Statistical Evaluation of Drug Safety Data.
AB  - There has been growing awareness of the importance of the statistical evaluation
      of drug safety data both in the premarketing and postmarketing settings. Careful
      and comprehensive approaches are warranted in safety evaluation. This paper
      offers a high-level review of some key issues and emerging statistical
      methodological developments. Specifically, the following topics are discussed:
      prospective program-level safety planning, evaluation, and reporting; the impact
      of adverse event grouping on statistical analysis; the applications of Bayesian
      methods in safety signal detection; meta-analysis for analyzing safety data; and
      safety graphics. Aspects related to benefit-risk assessments are also covered.

PMID- 30231416
TI  - Commentary: Statistics in Therapeutic Innovation and Regulatory Decision Making.

PMID- 30231417
TI  - Adaptive Clinical Trials: Overview of Phase III Designs and Challenges.
AB  - Adaptive designs use accruing data to make changes in an ongoing trial according
      to a prespecified plan and potentially offer great efficiencies for clinical
      development. There are many types of adaptive designs and many trial aspects that
      could in theory be adapted. However, the scope of adaptive designs with relevance
      in confirmatory trials is narrower, and in addition, extensive pre-planning is
      needed and various types of challenges need to be addressed in order to use these
      designs in this stage of development. Nevertheless, with careful planning, there
      are opportunities for these designs to offer important benefits even in the
      confirmatory stage of development. We provide an overview of adaptive designs
      that have relevance for confirmatory trials and discuss considerations that may
      affect whether they should or should not be used in particular trials or programs
      as well as the challenges that need to be addressed.

PMID- 30231418
TI  - Remaining Challenges in Assessing Non-Inferiority.
AB  - Despite decades of experience with non-inferiority trials, they remain a source
      of great controversy and involve fundamental areas of disagreement. Indeed, there
      can be little more fundamental than the definition of the hypothesis to be
      tested, and yet it can be argued that the null hypothesis commonly used in these
      trials, which involves specification of a non-inferiority margin, is the wrong
      one. Non-inferiority trials involve an indirect comparison between the
      experimental treatment under evaluation and placebo, but the null hypothesis
      based on a non-inferiority margin does not address this aspect of the trial's
      objective. In addition, the criterion in common use for concluding that the
      experimental treatment preserves a prespecified fraction of the control
      treatment's effect is in conflict with a reasonable criterion for preference of
      the experimental treatment over the control, and can lead to inconsistencies in
      drug approval decisions. This review discusses these issues and provides
      recommendations.

PMID- 30231419
TI  - Recent Developments in the Prevention and Treatment of Missing Data.
AB  - Recent research has fostered new guidance on preventing and treating missing
      data, most notably the landmark expert panel report from the National Research
      Council (NRC) that was commissioned by FDA. One of the findings from that panel
      was the need for better software tools to conduct missing data sensitivity
      analyses and frameworks for drawing inference from them. In response to the NRC
      recommendations, a Scientific Working Group was formed under the Auspices of the
      Drug Information Association (DIASWG). The present paper is from work of the
      DIASWG. Specifically, the NRC panel's 18 recommendations are distilled into 3
      pillars for dealing with missing data: (1) providing clearly stated objectives
      and causal estimands; (2) preventing as much missing data as possible; and (3)
      combining a sensible primary analysis with sensitivity analyses to assess
      robustness of inferences to missing data assumptions. Sample data sets are used
      to illustrate how sensitivity analyses can be used to assess robustness of
      inferences to missing data assumptions. The suite of software tools used to
      conduct the sensitivity analyses are freely available for public use at
      www.missingdata.org.uk.

PMID- 30231420
TI  - A Conditional Adaptive Weighted Test Method for Confirmatory Trials.
AB  - The authors consider a statistically valid method that has little concern caused
      by down weighting in stage 2 or slight loss in efficiency and possibly improves
      power performance for a trial design that allows for adaptation of statistical
      information. In addition to the need for a priori sound data-based planning that
      accounts for limited uncertainty, the criteria for statistical information
      adaptation are scientifically sound and can foster transparent trial logistics
      that are necessary for such adaptation in confirmatory trials. A major rationale
      of the proposed conditional adaptive weighted test method is to increase the
      probability of success of an adequate and well-controlled confirmatory trial that
      may otherwise fall short of statistical significance despite initial rigorous
      planning for statistical information.

PMID- 30231421
TI  - Adaptive Design Applied to Identification of the Minimum Effective Dose in
      Schizophrenia: Simulations of Scientific and Commercial Value.
AB  - The International Society for CNS Clinical Trials and Methodology (ISCTM)
      Adaptive Design Working Group (IADWG) designed a case study simulation exercise
      to compare the value of traditional versus adaptive design approaches to phase II
      clinical trial design in schizophrenia in statistical and economic terms.
      Operational characteristics of both designs were compared across 7 likely dose
      response curves. Based on IADWG members' recent research experience in
      schizophrenia, estimates of expected net present value (eNPV) for the molecule
      were compared for the traditional and adaptive designs. Across dose-response
      curve scenarios with a minimum effective dose (MED), the adaptive design was more
      likely to show proof of concept and correctly identify the MED than was the
      traditional design. Even with a conservative weighting of possible dose-response
      curves, using an adaptive design in phase II resulted in higher eNPV. This
      simulation supports the statistical and economic value for decision makers
      exploring the use of adaptive approaches to phase II research in schizophrenia.

PMID- 30231422
TI  - Dose-Response Determination in Multistage Endpoint Clinical Trials.
AB  - Improper dose selection remains one of the key drivers of the large attrition
      rates observed in confirmatory studies in clinical drug development. Many factors
      contribute to this problem, such as insufficient resources allocated to dose
      ranging studies and the use of statistical methods better suited for phase 3
      studies than for dose selection. This paper describes a model-based dose-finding
      method that leverages all longitudinal data collected in the trial to estimate
      the dose-response relationship at any desired visit, using it to estimate target
      doses of interest, such as the minimum dose producing a desired clinical benefit.
      The approach uses a Markov chain model to account for correlation in the repeated
      measures obtained on the same patient. An actual phase 2 study and simulations
      are used to illustrate the methodology.

PMID- 30231424
TI  - Editor-in-Chief's Commentary: Gene Penetrance, Therapeutic Targets, and
      Regulatory Science.

PMID- 30231423
TI  - A Review of Statistical Methods for Safety Surveillance.
AB  - The data-mining statistical methods used for disproportionality analysis of drug
      adverse event combinations from large drug safety databases such as the FDA's
      Adverse Event Reporting System (FAERS), consisting of spontaneous reports on
      adverse events for postmarket drugs, are called passive surveillance methods.
      However, the statistical signal detection methods for longitudinal data, as the
      data accrue in time, are called active surveillance methods. A review of the most
      commonly used passive surveillance statistical methods and the relationships
      among them is presented with unified notations. These methods are applied to the
      2006-2012 FAERS data; the number of drug signals of disproportionate rates (SDRs)
      detected by each of these methods with the common SDRs from all of these methods,
      for the adverse event myocardial infarction, are given. Finally, there is a brief
      discussion on the recently developed active surveillance methods.

PMID- 30231425
TI  - Summary of DIA Workshop on Co-Development of Personalized Medicine and In Vitro
      Diagnostic Companion Devices.
AB  - The pairing of personalized medicine, including targeted drug therapy, and in
      vitro diagnostic (IVD) companion devices (ie, "companion diagnostics") allows
      treatment decisions to be tailored for each patient. However, development of
      companion diagnostics and personalized medicine still faces challenges in
      clinical development as regulatory policy tries to keep up with and accommodate
      this growing field. To assist industry and regulators, the DIA provided a forum
      for the discussion of current challenges and opportunities for progressive
      alignment approaches to regulating personalized medicine and IVD devices.

PMID- 30231426
TI  - Associate Editor's Commentary: Measuring Responsibility.
AB  - The Access to Medicine Index (ATMi) is an attempt to measure and compare the
      corporate social responsibility of both innovator (20) and generics (7) companies
      based on a number of different (and often quixotic) indicators. According the
      Access to Medicine Foundation, the index "aims to help poor people in developing
      countries gain access to medicine by encouraging the pharmaceutical industry to
      improve its commitments and practices related to this issue." Since it's a
      comparison, the theory is that competition amongst companies will drive desirous
      "socially responsible" behaviors. A noble goal-but the devil is in the details.
      As Abraham Lincoln said, "You cannot escape the responsibility of tomorrow by
      evading it today."

PMID- 30231427
TI  - Achieving a Culture of Quality in Pharmaceutical Biostatistics: One Approach to
      Achieving Quality Deliverables.
AB  - Biostatistics units within the pharmaceutical industry are faced with the
      challenge of increasing productivity, reducing costs, and accelerating timelines
      while at the same time maintaining high quality. This paper describes how the
      global biostatistics unit in one company is addressing this challenge by
      nurturing a "culture of quality" to engage frontline staff responsible for daily
      deliverables. The approach ties together the measurement, improvement, and
      maintenance of quality, thus inviting staff to understand their role in achieving
      quality deliverables. Appointment within the operations unit of a quality lead,
      who is responsible for quality oversight, further increases visibility and
      contributes to the culture. Measurement is addressed through the use of a
      quarterly quality report card in which quality-related metrics are consolidated
      and tracked over time. Trends and outliers are explored. Through established
      process improvement practices, a Lean Sigma team tackles select high-value
      processes. Quality is maintained through continuous feedback loops driven by
      formal quality assurance audits and logs of lessons learned. This paper first
      considers how to define quality in this context; then addresses the sometimes
      disjointed areas of measurement, improvement, and maintenance; and ultimately
      ties them together to drive a culture of quality.

PMID- 30231428
TI  - Impact of In-Pharmacy Education on Patients' Knowledge and Attitudes About
      Clinical Trials.
AB  - The lack of public awareness and understanding about clinical research has long
      hindered the efficiency and speed in recruiting patients to participate in
      clinical trials. Earlier research conducted by the Center for Information and
      Study on Clinical Research Participation (CISCRP) examined whether pharmacists
      might be a viable channel to educate and engage the public about clinical
      research, and the results suggested that pharmacy-directed outreach and education
      are feasible. This study measured the impact of in-pharmacy education on patient
      comprehension and willingness to participate in clinical research. In
      collaboration with McKesson and its network of independent community pharmacies,
      CISCRP trained 32 pharmacists and provided them with educational materials to
      display and/or distribute at their pharmacies for a period of 2 to 3 months.
      Presurveys and postsurveys among 487 patients were conducted to gather baseline
      measures and to assess the impact of educational materials and in-pharmacy
      discussions. A postsurvey was also conducted among pharmacists. The results of
      the study show that patient discussions with their pharmacists and patient review
      of educational materials distributed through pharmacies positively impacted
      patient awareness, comprehension, and willingness to participate in clinical
      trials. Indeed, during the study period, 4% of patients who reviewed the
      materials chose to volunteer for clinical trials. Nearly all baseline measures of
      awareness and comprehension increased by 10 to 20 percentage points. Respondents
      were more interested in learning about clinical research after speaking with
      their pharmacists and reviewing educational materials, and 40% were more likely
      to recommend participation to a friend or family member.

PMID- 30231429
TI  - Drug Development in the 21st Century: The Synergy of Public, Private, and
      International Collaboration.
AB  - The traditional economic model for drug development by leading pharmaceutical
      companies in the developed world has yielded diminishing returns in recent years,
      with large pharmaceutical companies relying less on research and development and
      more on cost cutting and obtaining promising drug candidates through mergers and
      acquisitions. Concurrently, drug companies in emerging markets have flourished
      under a different economic model characterized by public-private partnerships,
      government subsidy, and profitable marketing of generic drugs. These companies
      are now focusing on research and development of innovative drug candidates,
      including drugs that treat neglected diseases such as tuberculosis and hepatitis.
      However, drug companies in developing countries may lack the expertise of leading
      drug companies to navigate the complicated regulatory system. This article
      highlights an opportunity for companies with drug development expertise to
      partner with companies in the developing world with innovative pipeline drugs.

PMID- 30231430
TI  - Product Registration in Developing Countries: A Proposal for an Integrated
      Regional Licensing System Among Countries in Regional Economic Blocs.
AB  - The product pipeline for diseases that disproportionately affect the developing
      world has considerably expanded over the last decade. Indeed, there are about 134
      products for these diseases in the pipeline, including vaccines, drugs,
      diagnostics, microbicides, and vector control tools, and dozens of these products
      are currently being evaluated in human trials in developing countries where the
      disease of interest exists. While these efforts are underway, the need to
      identify regulatory pathways for licensing these new products is becoming obvious
      to many manufacturers. In many developing countries, where the need of these
      products is greatest, the national regulatory authorities often lack the
      resources and regulatory capacity to review the registration dossiers to approve
      the use of new products. Given this challenge, new regulatory models are urgently
      needed to offset product registration. In this paper, we propose how regional
      regulatory frameworks established by regional harmonization initiatives can be
      used to set up an integrated regional licensing system, a system that will
      provide for a single product dossier application and a single review, leading to
      a single approval that will grant access to all the markets in the region. The
      proposed model aims at complementing the ongoing regional regulatory
      harmonization efforts by pooling the activities of different national expertise
      groups so as to make the best use of the available skills at a reduced cost. By
      sharing the various regulatory tasks in an integrated manner, the total process
      will be accelerated and will facilitate product registration in the region.

PMID- 30231431
TI  - Optimizing Drug Development Programs: Type 2 Diabetes Case Study.
AB  - Recently, consideration was given to the impact of dose selection strategies in
      phase IIb on the overall success of drug development programs. A natural next
      step is to simultaneously optimize design aspects of both phase IIB and phase
      III. We used type 2 diabetes as an example, including realistic regulatory and
      commercial scenarios for this indication. The expected net present value (eNPV)
      has been selected as the primary outcome because it naturally accommodates
      optimization, providing an explicit trade-off between the probability of success
      (PoS) and time delays and trial costs. Our findings are that larger studies
      and/or implementation of an adaptive design over a fixed design in phase IIb
      provide more precise dose selection and reduce the bias of treatment effects and
      uncertainty in the estimated eNPV within the range of sample sizes that we
      examined. Developers also have to ensure that dose selection criteria are
      consistent with development strategy and objectives.

PMID- 30231433
TI  - Transparency at the EMA: More Evidence Is Needed.
AB  - Ever since its establishment in 1995, the European Medicines Agency (EMA) has
      been committed to transparency. That said, as of late the Agency has been
      criticized for lacking it. To address this criticism, the Agency is attempting to
      become even more transparent. In this commentary the author argues that the EMA
      is now moving almost too quickly toward complete transparency. Before launching a
      number of new transparency initiatives, it should consider arranging some
      workshops on the topic as well as pretesting its communication messages before
      they are put in the public domain.

PMID- 30231432
TI  - Translation and Labeling in Europe: Thoughts on the Process and Organization for
      Efficient Translation Sourcing.
AB  - The constant adjustment of pharmaceutical labeling to accurately portray the
      benefit, risk, and appropriate usage is a task that will continue to grow.
      Coordination of multilingual text across the EU markets will remain a challenge,
      as will coordination with other global markets. Literally thousands of
      coordination and execution steps are done today in a highly manual and labor
      intensive way. The geographically and organizationally distributed stakeholders
      often follow largely diverting procedures. Managing global product information
      efficiently depends largely on how the central labeling group and the local
      affiliates organize their interaction. The availability, capacity, and skills of
      the local organizations; the product portfolio; the commercial value of a
      product; the commercial status of the target market; and status of the submission
      (new product vs maintenance work) influence how the thousands of multilingual
      tasks are best distributed among centers, affiliates, and external service
      providers. This paper provides guidelines on how the various methods of local
      control, local outsourcing, or central outsourcing can be best applied and what
      the potential risks of each of those methods are. The article further addresses
      the potential to significantly lower the workload through applying translation
      technologies and to increase the efficiency of coordinating global labeling
      maintenance.

PMID- 30231434
TI  - Defining Patient-Centricity: Opportunities, Challenges, and Implications for
      Clinical Care and Research.
AB  - The Patient-Centered Outcomes Research Institute (PCORI), created and funded by
      the Affordable Care Act, is charged with bringing the patient perspective to
      clinical research design and the outcomes that are studied. However, there is no
      consensus definition of "patient-centeredness" or "patient-centricity." This
      paper distinguishes between the terms and describes an infrastructure for
      supporting the concept of patient-centricity. The patient's role needs to be
      described in a way that makes it feasible to implement health care delivery and
      support parameters to conduct clinical research over a sustained period of time.
      The authors propose the use of a structured Practice-Based Clinical Research
      Network to perform patient-centered outcomes research consistent with the
      requirements of the pharmaceutical sector in a safe, ethical, and effective
      manner and congruent with the principles of Good Clinical Practice (GCP).

PMID- 30231435
TI  - Public Health Innovation: Biopharmaceuticals Lost in Translation?
AB  - Taking treatments from bench to bedside, or bench to community, requires a viable
      pathway connecting molecular science to global need through public and private
      research funding, clinical development, drug marketing, and policy making. In
      this paper, the authors present a systematic analysis of the effectiveness of
      translating basic science into reduced global burden of disease as a proxy for
      systemic public health impact. They pose a compound research question: Is the
      current drug development pipeline aligned with current and future global burden
      of disease, and, if not, where do the disconnections occur?

PMID- 30231436
TI  - Chronically Ill Czech Patients' Beliefs About Medicines: The Psychometric
      Properties and Factor Structure of the BMQ-CZ.
AB  - The main objective of this study was to assess the factor structure and
      psychometric properties of the Czech translation of the Beliefs about Medicines
      Questionnaire (BMQ-CZ). It was hypothesized that the 4-factor structure of the
      BMQ-CZ would be confirmed and that psychometric properties would be verified by
      using positive or negative correlations with self-reported adherence, illness
      perceptions, and medication statements. A total of 627 people were approached,
      and 467 agreed to participate. The sample included chronically ill patients as
      well as patients seeking allopathic and homeopathic care. As a measure of
      criterion-related validity, the BMQ-CZ was administered along with the translated
      Czech versions of the Medication Adherence Report Scale (MARS-CZ) and the Brief
      Illness Perception Questionnaire (Brief IPQ-CZ) and additional assertions. The
      factor structure, reliability, and validity of the BMQ-CZ were evaluated. The
      internal consistency of the BMQ-CZ was satisfactory (Cronbach alpha = .69-.85). A
      factor analysis supported the BMQ-CZ's 4-factor structure, and the concurrrent
      validity of the BMQ-CZ was supported by positive correlations with self-reported
      measures of adherence and beliefs about medicines and disease. The BMQ-CZ
      demonstrated sufficient psychometric performance as a self-reported measure of
      medication beliefs among patients with hypertension, diabetes, and rheumatic
      disease.

PMID- 30231438
TI  - A Model for the Role of TIRS in Helping to Develop and Validate Best Practices
      Across Clinical Trial Management.

PMID- 30231437
TI  - Training New-Hire Medical Information Specialists in the Pharmaceutical Industry:
      A Benchmarking Survey.
AB  - Most pharmaceutical and biotechnology companies have a medical information (MI)
      department staffed by medical information specialists (MISs); to ensure that MISs
      perform their role in an accurate and compliant manner, companies must have
      robust training processes in place. The primary objective of this study was to
      benchmark the training processes for new-hire MISs in the pharmaceutical industry
      as well as their training preferences. Nineteen respondents from 19 companies
      completed a web-based survey, which resulted in a 41.3% response rate. These
      companies represented a variety of MI department sizes and number of products
      supported. Eighty-four percent (16/19) of companies had structured new-hire
      training processes in place. Approximately two-thirds of all respondents
      preferred live training on new-hire training topics. After completion of new-hire
      training, several companies (10/18) offered ongoing refresher training to their
      MISs. The results indicate that companies may benefit from having structured new
      hire training procedures and tailoring training to MIS learning preferences.

PMID- 30231439
TI  - The Imperfect Intellectual Bridge Between a Master Medicinal Product and Its
      Associated Custom-Made Medicinal Products.
AB  - To obtain a license to be placed on the marketplace, a medicinal product must be
      accompanied by data on quality and data from preclinical studies and studies of
      clinical safety and efficacy. At the time of first production, a custom-made
      medicinal product will have data on quality but will not be accompanied by data
      from preclinical studies or from studies of clinical safety and efficacy. To span
      the gap in data, an "imperfect intellectual bridge" between data for a custom
      made medicinal product and data for its master medicinal product is described.
      The imperfect intellectual bridge will allow the custom-made medicinal product to
      draw on data associated with its master medicinal product. In time, it may be
      possible for a custom-made medicinal product to transfer to an independent
      license after collection of data on clinical safety and efficacy by means of a
      pharmacovigilance exercise.

PMID- 30231440
TI  - Technology Considerations to Enable the Risk-Based Monitoring Methodology.
AB  - TransCelerate BioPharma Inc developed a methodology based on the notion that
      shifting monitoring processes from an excessive concentration on source data
      verification to comprehensive risk-driven monitoring will increase efficiencies
      and enhance patient safety and data integrity while maintaining adherence to good
      clinical practice regulations. This philosophical shift in monitoring processes
      employs the addition of centralized and off-site mechanisms to monitor important
      trial parameters holistically, and it uses adaptive on-site monitoring to further
      support site processes, subject safety, and data quality. The main tenet is to
      use available data to monitor, assess, and mitigate the overall risk associated
      with clinical trials. Having the right technology is critical to collect and
      aggregate data, provide analytical capabilities, and track issues to demonstrate
      that a thorough quality management framework is in place. This paper lays out the
      high-level considerations when designing and building an integrated technology
      solution that will aid in scaling the methodology across an organization's
      portfolio.

PMID- 30231441
TI  - Site Characteristics Influencing the Translation of Clinical Research Into
      Clinical Practice.
AB  - Investigative sites participating in clinical trials play an instrumental role in
      aiding market adoption. Site experiences in clinical research help physician
      investigators and research professionals gain familiarity with and exposure to
      investigational treatments. This knowledge may be passed on to sponsor companies
      and may ultimately assist in positioning new products and driving
      commercialization success. This study evaluates site characteristics that
      influence the acquisition and sharing of knowledge gained through clinical trial
      experience. The impact of 2 central site characteristics on the process of
      translating drug experience is assessed: site location (North America/rest of the
      world) and site type or setting (academic/independent). The results show that
      investigative sites located outside North America generate and share more
      knowledge than those within North America. Furthermore, although both academic
      and independent sites generate the same level of knowledge, academic sites share
      more of this knowledge with sponsor companies. This study suggests new strategies
      that sponsors can leverage to drive greater transfer of clinical research
      knowledge into clinical practice and ultimately improve the commercialization of
      newly launched therapies.

PMID- 30231442
TI  - Defining a Central Monitoring Capability: Sharing the Experience of TransCelerate
      BioPharma's Approach, Part 1.
AB  - Central monitoring, on-site monitoring, and off-site monitoring provide an
      integrated approach to clinical trial quality management. TransCelerate
      distinguishes central monitoring from other types of central data review
      activities and puts it in the context of an overall monitoring strategy. Any
      organization seeking to implement central monitoring will need people with the
      right skills, technology options that support a holistic review of study-related
      information, and adaptable processes. There are different approaches actively
      being used to implement central monitoring. This article provides a description
      of how companies are deploying central monitoring, as well as samples of the
      workflows that illustrate how some have implemented it. The desired outcomes
      include earlier, more predictive detection of quality issues. This paper
      describes the initial implementation steps designed to learn what organizational
      capabilities are necessary.

PMID- 30231444
TI  - Patient Comprehension of Medication Guides for Asthma and Chronic Obstructive
      Pulmonary Disease Medications.
AB  - PURPOSE: This study assessed patients' comprehension of the Advair and Serevent
      medication guides (MGs) and MG reading behaviors with the goal to improve risk
      communication. METHODS: After reading their assigned MGs, 452 adults with asthma
      or chronic obstructive pulmonary disease participated in structured interviews to
      assess comprehension of safety risks in the Advair MG (asthma, n = 150; chronic
      obstructive pulmonary disease, n = 153) and Serevent MG (asthma, n = 149).
      Generalized estimating equations for correlated binary data were used to identify
      factors associated with correct responses. RESULTS: For 10 of 12 individual risk
      questions, >=75% of patients reported correct responses. After adjusting for
      patient characteristics, health literacy was significantly associated with
      correct responses (odds ratio = 1.03, 95% confidence interval = 1.02-1.05 per 1
      point increase in the Rapid Estimate of Adult Literacy in Medicine). MG reading
      behaviors were inconsistent, with many patients reading MGs only once (40%)
      despite multiple prescriptions. CONCLUSIONS: Comprehension of safety risks in the
      Advair and Serevent MGs was adequate for most patients in the study but decreased
      with health literacy. Initiatives to improve patient-directed risk communication
      should consider health literacy and reasons for inconsistent reading behaviors.

PMID- 30231443
TI  - Promotion of Patient-Reported Outcome Label Claims Based on Nonprimary Endpoints.
AB  - INTRODUCTION: Patient-reported outcomes (PROs) play an increasingly pivotal role
      in confirmatory clinical trials with pressures to develop drug differentiation
      strategies. Claims based on primary endpoints that are included in the product
      label are likely to be fully promoted by the manufacturers; however, the extent
      to which manufacturers promote claims based on secondary PRO endpoints is
      unknown. The purpose of this review is to assess the extent of promotion of PRO
      label claims for 6 pharmaceutical products with nonprimary PRO endpoints.
      METHODS: Six products were reviewed that received PRO label claims based on
      nonprimary PRO endpoints between 2006 and 2008. Promotional documents distributed
      in the United States by the drug manufacturers between the year of launch and
      2011 were identified from a PharmaVoxx database. Circulation of these documents
      was calculated according to quarterly distributions. Two researchers reviewed the
      documents using standard criteria. Promotional activities based on nonprimary PRO
      endpoint claims were compared with total number of messages. RESULTS:
      Manufacturers of the 6 products distributed 973 unique promotional documents 2998
      times. Messages based on primary endpoints were distributed 1798 times, whereas
      messages relating to nonprimary PRO endpoints were distributed 1200 times (40% of
      distributions) and varied among products (4%-70%). Messages relating to PROs were
      targeted mostly at patients and consumers (65%) versus physicians and health care
      professionals (34%). CONCLUSIONS: Promotion of PRO messages based on nonprimary
      endpoints is much lower than those based on primary endpoints, suggesting that
      manufacturers do not always optimize the potential of PRO messages.

PMID- 30231445
TI  - Approval Status and Regulatory Actions for Radiopharmaceuticals in the United
      States and Japan.
AB  - The aim of this study was to identify the differences between Japan and the
      United States in the approval status and regulatory actions for
      radiopharmaceuticals. The package inserts of radiopharmaceuticals that have been
      approved in the United States and Japan were used to investigate the status of
      approval in each country, examining the similarities and differences thereof and
      taking the regulatory systems of the 2 countries into account. Results revealed
      that since 1995, fewer products have been approved in Japan than in the United
      States: 16 radiopharmaceuticals have been approved in the United States, compared
      to only 7 in Japan. Although the clinical evaluation methodology for
      radiopharmaceuticals is still being developed, study results suggest that
      international harmonization of the regulatory systems and manufacturing controls
      for positron emission tomography drugs will be important for the development of
      such drugs in multinational countries, including Japan.

PMID- 30231446
TI  - A New Method for the Comparison of Powers of Noninferiority Exact Tests for the
      Difference of Proportions.
AB  - Noninferiority tests for comparing 2 proportions are frequently used in clinical
      trials to prove that a new drug with few side effects or low cost is not
      significantly inferior in efficacy to the standard drug. In the literature, the
      reported comparisons of powers of noninferiority tests are based on simulations
      or gross approximations. By using the concept of "mean power," Martin-Andres and
      Silva-Mato developed a new method to compare the powers of superiority tests for
      the difference of proportions. In the present article, this method is extended to
      the comparison of powers of noninferiority exact tests for trials with equal
      sample sizes. To illustrate this new method, we have compared 2 popular
      noninferiority exact tests for the difference of proportions: the likelihood
      ratio test and the Farrington-Manning test. The conclusion is that the likelihood
      ratio test has greater mean power than the Farrington-Manning test.

PMID- 30231447
TI  - FDA Studies New Strategies for Presentation of Patient Information.

PMID- 30231448
TI  - Just Say No?

PMID- 30231449
TI  - FDA Analysis of Atorvastatin Products Refutes Report of Methyl Ester Impurities.

PMID- 30231450
TI  - Building an Integrated Early Clinical Development Platform to Improve the Path to
      Proof of Concept.
AB  - Probability of success in phase II dominates the drug development cost calculus,
      with phase I/II as the critical juncture for proof of concept. Failure to address
      fundamental pharmacologic questions in early development is alarmingly frequent
      and a strong predictor of failure. Safety, manufacture, formulation, and
      commercialization issues are also vital. Systems biology provides a framework to
      analyze genomic, proteomic, and metabolomic data and construct complex network
      models of molecular pathophysiology. Biomarkers offer the largest learning
      opportunity, and combined adaptive protocol designs provide a lean but
      scientifically robust path to proof of concept. The traditional model of phase I
      study execution in a clinical pharmacology unit is evolving to a networked model
      of an integrated early clinical development platform. The power of this platform
      is enhanced with a proactive multidisciplinary approach to quality and safety,
      including lean 6 sigma tools and simulations.

PMID- 30231451
TI  - Responsible Parties-Is It Time to Clean Up Your ACTs?
AB  - This brief study examined applicable clinical trials (ACTs) registered in the
      ClinicalTrials.gov website that may be considered by the Food and Drug
      Administration to be noncompliant and subject to enforcement penalties after the
      Food and Drug Administration Amendments Act of 2007 rulemaking, anticipated in
      2014. Prior literature verifies the existence of ACT recordkeeping issues. The
      results of this simple analysis are valuable with providing baselines for the
      tracking of record maintenance trends because no documented prior analyses could
      be located. Ascertaining which registered studies meet the criteria of an ACT is
      quite difficult because there is no element in each ClinicalTrials.gov record
      specifically indicating as much. Neither is there an element in each record
      indicating whether trial sponsors have received an extension from the National
      Institutes of Health (NIH) to delay reporting study results that exceed the
      regulatory mandated timeline of 12 months after the "primary completion date"
      element. Therefore, studies that meet the fundamental criteria for being an ACT
      were extracted through the ClinicalTrials.gov database advanced search function.
      The extracted records were downloaded to an Excel spreadsheet to filter for the
      intervention types of biologics, devices, and drugs. Advanced search filtering
      procedures yielded 39,564 records. From this pool of "potential ACT" records, 2
      noncompliance issues were extracted: first, studies that had not been updated in
      2 years and were marked by the NIH as "unknown"; second, studies that were marked
      by the responsible party as "completed" or "terminated" but did not have any
      results posted 12 months after the primary completion date. This resulted in a
      total of 13,060 (33%) potential ACT records identified as being at risk for
      having noncompliance issues. The idea behind this article was substantiated-that
      maintenance of ACT records in the ClinicalTrials.gov database needs to improve.
      Responsible parties are urged to avoid FDA issued noncompliance penalties, by
      ensuring that all their ACT records are updated and regulatory compliant prior to
      the rulemaking that is on the agenda for 2014. Sponsors can accomplish this by
      developing standard operating procedures that facilitate proper study
      registration, routine updates of ongoing ACT records, and timely posting of study
      results. Using regulatory requirements and NIH guidelines, ideas are provided for
      improving recordkeeping practices, data disclosure timeliness, and the structure
      of the records found in ClinicalTrials.gov.

PMID- 30231452
TI  - Novel Statistical Designs for Phase I/II and Phase II Clinical Trials With Dose
      Finding Objectives.
AB  - In modern drug development, there has been an increasing interest in adaptive
      clinical trials-research designs that allow judicious modification of certain
      aspects of an ongoing clinical trial based on prespecified criteria according to
      accumulating data to achieve predetermined experimental objectives. A
      particularly important application of adaptive designs is in phase I and II
      stages of drug development. Many novel adaptive designs have been proposed in the
      context of phase I oncology trials of cytotoxic agents where acceptable toxicity
      frequently translates into therapeutic response. However, an assessment of
      efficacy measurements based on biomarkers in early development is also very
      important. The current paper gives an overview of adaptive designs for early
      development studies that utilize efficacy measurements in design adaptation
      rules. These include seamless phase I/II designs, where efficacy and safety
      considerations are both incorporated in dose-finding objectives, and phase II
      dose-response studies, which typically aim at establishing a dose-response
      relationship with respect to some efficacy outcome and at identifying the most
      promising doses to be tested in subsequent confirmatory trials. The authors
      discuss statistical, logistical, and regulatory aspects of these designs and
      provide perspectives on their applications in modern clinical trials.

PMID- 30231453
TI  - Exploring Ethnic Differences in Toxicity in Early-Phase Clinical Trials for
      Oncology Drugs.
AB  - During oncology drug development, it is important that ethnic differences are
      evaluated to determine the optimal dose and administration schedule in a new
      region based on the clinical data from other regions. The objective of this study
      was to explore the possibility of detecting ethnic differences in toxicity during
      early-phase clinical trials. Data were reviewed from phase I clinical trials for
      new drug applications conducted in Japan and Western countries. The maximum
      tolerated doses (MTDs), recommended phase II doses (RP2Ds), and approved doses in
      Japan were compared with those in Western countries. There were 4 of 28 drugs
      eligible for analysis that showed differences in MTDs or RP2Ds between Japanese
      and Western patients. Differences in MTDs or RP2Ds in 2 phase I trials were
      associated with ethnic differences in toxicity. It may be worthwhile to evaluate
      ethnic differences in toxicity during early-phase clinical trials for oncology
      drugs.

PMID- 30231454
TI  - Structured Approaches to Benefit-Risk Assessment: A Case Study and the Patient
      Perspective.
AB  - Assessing the utility of structured approaches to benefit-risk assessment of
      medicinal products is challenging, in part due to the lack of a gold standard for
      results and the uncertainty inherent in the data. In place of conducting formal
      testing, obtaining feedback from users of structured approaches provides insight
      into their value and limitations. The authors conducted a simulated single
      session benefit-risk decision in which 3 groups applied the PhRMA
      BRAT(Pharmaceutical Research and Manufacturers of America Benefit-Risk Action
      Team) framework or the multicriteria decision analysis approach. The groups were
      provided with background and data for a hypothetical triptan for acute migraine
      in a population with cardiovascular risk factors and were asked to determine and
      defend an approval decision. Three insights emerged consistently from the groups:
      (1) the value of a structured approach to benefit-risk assessment, (2) the
      clarity provided by real-time visualization tools, and, most critically, (3) the
      importance of bringing the patient into the discussion early.

PMID- 30231455
TI  - Statistical Properties of Large Sample Tests for Dose Content Uniformity.
AB  - The European Union (EU) test for uniformity of dosage units using large sample
      sizes was published in European Pharmacopoeia 7.7 in 2012. There are 2
      alternative tests. Option 1 is a parametric two-sided tolerance interval-based
      method modified with an indifference zone and counting units outside of (0.75 M,
      1.25 M) (here, M is defined by sample mean, [Formula: see text], as M = 98.5% if
      [Formula: see text] < 98.5%, M = 101.5% if [Formula: see text] > 101.5%, and M =
      [Formula: see text] otherwise). Option 2 is a nonparametric counting method with
      an additional indifference-zone concept. The authors extended the parametric two
      one-sided tolerance interval-based method that was proposed for dose content
      uniformity testing based on 30 tablets to large sample sizes with the restriction
      that all operating characteristic curves of the two one-sided tolerance intervals
      for any given sample size intersect with the operating characteristic curve of
      the US Pharmacopoeia harmonized method for a sample size of 30 at the acceptance
      probability of 90% when the individual tablets with on-target mean are assumed to
      be normally distributed. This paper studies the acceptance probabilities in
      relation to the batch mean and batch standard deviation among the 2 EU options
      and the authors' proposed method. The acceptance probabilities of EU options 1
      and 2 and the proposed method were compared using simulation; results revealed
      that both EU options 1 and 2 produce larger acceptance probabilities when the
      batch mean is off-target. Furthermore, for a given standard deviation, the
      acceptance probability of EU option 2 at a mean 102% of the label claim is larger
      than that at a mean of 100% of the label claim under the normality assumption.

PMID- 30231456
TI  - Diabetic Patients' Knowledge of Their Disease, Therapeutic Goals, and Self
      management: Association With Goal Attainment at Dessie Referral Hospital,
      Ethiopia.
AB  - PURPOSE: This study aims to assess diabetic patients' knowledge of their disease,
      therapeutic goals, self-management, and its association with goal attainment at a
      hospital in Ethiopia. METHODS: A prospective cross-sectional study was conducted
      from February to March 2012 at the diabetic follow-up clinic of Dessie Referral
      Hospital. Diabetic patients who came for their diabetic follow-up were included
      consecutively until a calculated sample size of 303 was obtained. Data were
      collected by face-to-face interview through a pretested structured questionnaire
      and by medical record review. Binary logistic regression analysis was used to
      determine predictors of fasting glycemic control. RESULTS: Ninety-nine patients
      (32.7%) had poor knowledge about their disease. The average fasting blood glucose
      was 226.57 +/- 85.86 mg/dL, and only 61 patients (20.1%) achieved the recommended
      fasting glycemic goal (70-130 mg/dL). Diabetic patients who had poor knowledge
      were 5.53 times (95% confidence interval [CI]: 1.85, 16.49) more likely to not
      attain fasting glycemic goal compared to those who had good knowledge. Patients
      who did not practice self-monitoring of blood glucose were 3.09 times (95% CI:
      1.33, 7.21) more likely to not attain fasting glycemic goal than those who
      practiced. Failure to achieve fasting glycemic goal was 2.43 times (95% CI: 1.15,
      5.13) more common among patients who did not regularly exercise as compared to
      those who did. Patients who did not adhere to their medication were 3.72 times
      (95% CI: 1.69, 8.20) more likely to fail to achieve fasting glycemic goal
      compared to those who adhered to their medication. CONCLUSIONS: Fasting glycemic
      control was below the recommended standard among the study participants. Glycemic
      control was poor among patients who had poor knowledge, did not practice self
      monitoring of blood glucose, did not participate in regular exercise, and were
      nonadherent to their medication. This study population had poor knowledge about
      their disease.

PMID- 30231457
TI  - A comparative review and analysis of tentative ecological quality objectives
      (EcoQOs) for protection of marine environments in Korea and China.
AB  - Ecological quality objectives (EcoQOs), as tools for implementing ecosystem
      approach, have long been acknowledged to protect the marine ecosystems and
      fisheries in regional seas through joint efforts by surrounding countries over
      the past decade. The present review analyzed the best available meta-data
      relating to the five ecosystem elements that were recently proposed by the
      Northwest Pacific Action Plan to evaluate the current status of coastal ecosystem
      health in marine environment of the Yellow Sea. We suggested the six tentative
      EcoQOs among five ecological quality elements including: 1) biological and
      habitat diversity; 2) invasive species; 3) eutrophication; 4) pollutants; and 5)
      marine litters. Environmental status was assessed, depending on the EcoQOs
      targets, by comparison to the world average values, existing environmental
      standards, or reported values of other regional seas. Results of analysis
      revealed that among the six tentative EcoQOs, two target objectives to marine
      biodiversity and concentrations of nutrients (viz., DIN and DIP) were met towards
      good environmental status. Whilst, three EcoQOs relating to hypoxia and red-tide,
      pollutants (persistent toxic substances and metals), and marine litters
      (including microplastics) did not meet and one relating to invasive species could
      not be judged due to insufficient data sets. The biggest weak point for
      developing suitable EcoQOs and assessing status of ecosystem health could be
      insufficient meta-data sets available and/or discrepancy in methodological
      details cross the data-sets or between the two targeted countries. Thus, the
      cooperation of neighboring countries, viz., Korea and China for the Yellow Sea,
      is necessary for the ecosystem based management of our regional sea in the
      future. Overall, this first time review for the assessment of target tentative
      EcoQOs in the Yellow Sea region encompassing coasts of Korea and China would
      provide a better understanding of the current status of environmental pollution
      and ecosystem health.

PMID- 30231458
TI  - Coastal landscape planning for improving the value of ecosystem services in
      coastal areas: Using system dynamics model.
AB  - Coastal areas provide important ecosystem services and affect local tourism.
      However, these areas are also sensitive to coastal erosion. The purpose of this
      study was to simulate a landscape plan scenario to improve the value of ecosystem
      services. The Shinduri coastal area in South Korea which has important natural
      resources, such as coastal sand dunes and coastal forests. To simulate landscape
      changes, this study was conducted using system dynamics. The study progressed in
      three stages: first, an analysis of the landscape change behavior model of
      Shinduri in its current state and an evaluation of the value of ecosystem
      services was conducted. Second, a simulation was carried out by applying a
      coastal erosion scenario. Third, a simulation of landscape change was run, and
      the value of ecosystem services was estimated, with regard to afforestation,
      thinning, weeding and coastal sand dune restoration plan scenarios. The results
      were as follows: in the absence of disturbances, current landscape change models
      are stable, and the value of ecosystem services, which was $859,259 in 2014, has
      increased over time. However, the value of ecosystem services decreased when
      subjected to a coastal erosion scenario. The evaluation of value of ecosystem
      services under afforestation, thinning, weeding and coastal sand dune plan
      scenarios revealed an optimal landscape plan that focuses on a coastal sand dune
      restoration plan suggesting restoration of these dunes at a rate of 27.05 ha per
      year. When the coastal sand dune restoration plan is applied, the value of
      ecosystem services increases to $ 895,474 by 2054. The coastal sand dune
      restoration plan should prioritize the protection of the coastal sand dune area
      as component of the restoration of coastal ecological resources in the area.
      These findings could contribute to the ecological management and improvement of
      coastal ecosystem services.

PMID- 30231459
TI  - Rainfall effects on the erodibility of sediment and microphytobenthos in the
      intertidal flat.
AB  - The frequent rainfall during the low tide would erode and transport the surface
      sediment and microphytobenthos (MPB) in the intertidal flat. In order to quantify
      the rainfall effects on the erodibility of sediment and MPB at the salt marsh and
      mixed flat, a series of erosion experiments have been conducted with a Gust
      erosion microcosm system. Surface sediments were sampled for analyzing algal
      biomass (Chl-a) and primary production (PP) during three typical weather (without
      rain, rain, and post-rain) conditions. The results of erosion experiment, in both
      salt marsh and mixed flat, showed that the sediment erodibility under rain
      condition was higher than that under without rain condition, with increased total
      eroded mass by 37-86%. It indicated that the rainfall effects caused to
      significantly disturb the surface sediment. After the rainfall events, the
      removal of highly-erodible sediments resulted in the reduction in eroded mass.
      The MPB erodibility under rain condition was lower than that under without rain
      condition, with decreased total eroded Chl-a by 29%. At the mixed flat, the
      rainfall effects caused to significantly decrease biological activities of MPB
      (biomass and PP) associated with surface sediment. The surface Chl-a
      concentration under post-rain condition decreased by 73%, compared to that under
      rain condition. At the salt marsh, in contrast, the rainfall effects were barely
      shown when the biological activities of MPB were rather stable. This implied that
      the eroded MPB induced by rainfall was retained within the marsh system due to
      vegetation canopy.

PMID- 30231460
TI  - Seasonal and annual variations in removal efficiency of perfluoroalkyl substances
      by different wastewater treatment processes.
AB  - Municipal wastewater treatment plants (WWTPs) are important in the migration and
      transformation of perfluoroalkyl substances (PFASs) in water bodies. Six
      municipal WWTPs located in the upper reaches of the Guanting reservoir, along the
      Yanghe River, were sampled from November 2016 to July 2017. Influents, effluents,
      and activated sludge solutions were sampled and the concentrations of 17 PFASs
      were analyzed. Perfluorobutanoic acid (PFBA), Perfluorooctanoic acid (PFOA),
      Perfluorohexanoic acid (PFHxA), Perfluoropentanoic acid (PFPeA), Perfluorobutane
      sulfonat (PFBS) and Perfluorooctane sulfonate (PFOS) accounted for more than 90%
      of these. Seasonal variations in PFASs in influent directly influenced
      concentrations in supernatant and effluent. The annual average PFAS
      concentrations were 46.4, 45.1, and 38.5 ng L-1 in influent, supernatant, and
      effluent, respectively, indicating that WWTPs do not efficiently remove PFASs
      from wastewater. Annual average PFAS removal efficiencies differed among WWTPs,
      were influenced primarily by the treatment process used at each, and followed the
      order Cyclic Activated Sludge System (CASS, 32.2%) > Orbal Oxidation Ditch (OD,
      17.5%) > Anaeroxic-Anoxic-Oxic (A2/O, -1.49%). Short-chain PFASs were removed
      significantly more efficiently in the CASS compared to the other systems. These
      results can show how traditional wastewater treatment plants can help remove
      PFASs from the environment.

PMID- 30231461
TI  - The Effect of Gradient Bias Design on Electrochemistry and Tribology Behaviors of
      PVD CrN Film in a Simulative Marine Environment.
AB  - CrN films with various bias voltage designs (-20, -50, -80, -20~-80 V gradient
      change) were prepared via arc ion plating. Scanning electron microscope (SEM), X
      ray diffraction (XRD), nanoIndentor, electrochemistry workstation and tribo-meter
      were selected to evaluate the microstructure, mechanics, electrochemistry and
      tribology behaviors of as-prepared specimens in a simulative marine environment.
      By comparison, the adhesion force and anti-corrosion ability of CrN film with a
      gradient bias design were greatly enhanced compared with other films. The
      tribology behaviors of as-prepared specimens under various normal loads and
      sliding frequencies were deeply discussed. The result showed that the bias design
      played a critical role to impact the friction and wear behavior of film.
      Meanwhile, the CrN film with gradient bias design could bear a load of 25 N while
      other single CrN films failed, implying the strongest load-bearing capacity.
      Furthermore, at the same test condition, the lowest friction coefficient (COF)
      and wear loss were observed for CrN film with a gradient bias design, implying
      outstanding anti-friction and anti-wear abilities.

PMID- 30231462
TI  - Role of Magnesium Perrhenate in an Oil/Solid Mixed System for Tribological
      Application at Various Temperatures.
AB  - Magnesium perrhenate used as a lubricating additive was prepared by an aqueous
      solution method in this paper, and was suspended in a base oil poly alpha olefin
      (PAO6) with the aid of surface active agents (SA). The thermal stability of the
      mixed oil with/without magnesium perrhenate and surface active agents was
      investigated by thermogravimetry testing. The influences of magnesium perrhenate
      as solid lubricating additive on the extreme pressure performance and the
      friction-reducing properties over a wide temperature range of the mixed
      lubricants were determined by four-ball tests and ball-on-disc frictional tests
      for the commercially available silicon nitride ball and a Ni-base superalloy
      frictional pair. The results revealed that the added magnesium perrhenate did not
      obviously affect the thermostability and oxidation resistance of the base oil.
      Meanwhile, it minimized the coefficients of friction and wear scar diameter to a
      certain extent in the four-ball experimental conditions. Ball-on-disc rubbing
      tests suggested the mixed oil had a similar lubricating performance to the base
      oil below the decomposition temperature point. The most significant advancement
      was the impressive antifriction improvement at the high temperature range, while
      the friction coefficients of the oil containing magnesium perrhenate compound
      were obviously below that of the base stock. This better tribological performance
      of the mixed lubricant was attributed to the native shear susceptible property
      and chemical stability of magnesium perrhenate under high temperature conditions,
      which could form an effective durable and stable antifriction layer with the
      oxides from the superalloy matrix, thereby decreasing the friction in the high
      temperature environment.

PMID- 30231463
TI  - Individual Differences in the Perception of Color Solutions.
AB  - The color of food is important for flavor perception and food selection. The aim
      of the present study was to evaluate the visual color perception of liquid
      samples among Finnish adult consumers by their background variables. Participants
      (n = 205) ranked six different colored solutions just by looking according to
      four attributes: from most to least pleasant, healthy, sweet and sour. The color
      sample rated most frequently as the most pleasant was red (37%), the most healthy
      white (57%), the most sweet red and orange (34% both) and the most sour yellow
      (54%). Ratings of certain colors differed between gender, age, body mass index
      (BMI) and education groups. Females regarded the red color as the sweetest more
      often than males (p = 0.013) while overweight subjects rated the orange as the
      sweetest more often than normal weight subjects (p = 0.029). Personal
      characteristics may be associated with some differences in color associations.

PMID- 30231465
TI  - A Facile Synthesis Procedure for Sulfonated Aniline Oligomers with Distinct
      Microstructures.
AB  - Well-defined sulfonated aniline oligomer (SAO) microstructures with rod and flake
      morphologies were successfully synthesized using an aniline and oxidant with a
      molar ratio of 10:1 in ethanol and acidic conditions (pH 4.8). The synthesized
      oligomers showed excellent dispersibility and assembled as well-defined
      structures in contrast to the shapeless aggregated material produced in a water
      medium. The synergistic effects among the monomer concentration, oxidant
      concentration, pH, and reaction medium are shown to be controlling parameters to
      generate SAO microstructures with distinct morphologies, whether micro sheets or
      micro rods.

PMID- 30231464
TI  - Bioactive Compounds from Marine Organisms: Potential for Bone Growth and Healing.
AB  - Marine organisms represent a highly diverse reserve of bioactives which could aid
      in the treatment of a wide range of diseases, including various musculoskeletal
      conditions. Osteoporosis in particular would benefit from a novel and effective
      marine-based treatment, due to its large disease burden and the inefficiencies of
      current treatment options. Osteogenic bioactives have been isolated from many
      marine organisms, including nacre powder derived from molluscan shells and
      fucoidan-the sulphated polysaccharide commonly sourced from brown macroalgae.
      Such extracts and compounds are known to have a range of osteogenic effects,
      including stimulation of osteoblast activity and mineralisation, as well as
      suppression of osteoclast resorption. This review describes currently known
      soluble osteogenic extracts and compounds from marine invertebrates and algae,
      and assesses their preclinical potential.

PMID- 30231467
TI  - Smartphone-Based Microfluidic Colorimetric Sensor for Gaseous Formaldehyde
      Determination with High Sensitivity and Selectivity.
AB  - Formaldehyde is one of the most dangerous air pollutants, which can cause sick
      building syndrome. Thus, it is very crucial to precisely determine formaldehyde
      with a low cost and simple operation. In this paper, a smartphone-based
      microfluidic colorimetric sensor is devised for gaseous formaldehyde
      determination with high sensitivity and selectivity. Specifically, a novel
      microfluidic chip is proposed based on the 4-aminohydrazine-5-mercapto-1,2,4
      triazole (AHMT) method to determine formaldehyde; the chip consists of two
      reagent reservoirs, one reaction reservoir and a mixing column. In this design to
      prevent the fluid from flowing out while letting the gas molecule in, a
      hydrophobic porous poly tetra fluoroethylene (PTFE) membrane is put on the top of
      the reaction reservoir. Using the microfluidic chip sensor, a smartphone-based
      formaldehyde determination system is developed, which makes the measuring process
      automated and simple. As per the experiment results, the limit-of-detection (LOD)
      of the system is as low as 0.01 ppm, which is much lower than the maximum
      exposure concentration (0.08 ppm) recommended by the World Health Organization
      (WHO). Moreover, the sensor is hardly affected by acetaldehyde, volatile organic
      compounds (VOCs) or acidic-alkaline, which shows great selectivity. Finally, the
      performance of the proposed sensor is verified by using it for the determination
      of formaldehyde in a newly decorated house.

PMID- 30231468
TI  - Preparing the Degradable, Flame-Retardant and Low Dielectric Constant
      Nanocomposites for Flexible and Miniaturized Electronics with Poly(lactic acid),
      Nano ZIF-8@GO and Resorcinol Di(phenyl phosphate).
AB  - Degradable, flame retardant, and flexible nanocomposite films with low dielectric
      constant were prepared with poly (lactic acid) (PLA), nano ZIF-8@GO, and
      degradable flame-retardant resorcinol di(phenyl phosphate) (RDP). The SEM results
      of the fractured surfaces indicated that ZIF-8@GO and RDP were dispersed
      uniformly in the PLA matrix. The prepared films had good mechanical properties
      and the tensile strength of the film with 1.5 wt% of ZIF-8@GO was increased to
      48.2 MPa, compared with 38.5 MPa of pure PLA. Meanwhile, the nanocomposite films
      were flexible due to the toughing effect of RDP. Moreover, above 27.0% of limited
      oxygen index (LOI) and a VTM-0 rating were achieved for the nanocomposite films.
      The effects of nano ZIF-8@GO hybrids and RDP on the dielectric properties were
      investigated, and the results showed that ZIF-8@GO and RDP were beneficial in
      reducing the dielectric constant and dielectric loss of the nanocomposites.

PMID- 30231466
TI  - Effects of Long-Term Walnut Supplementation on Body Weight in Free-Living
      Elderly: Results of a Randomized Controlled Trial.
AB  - Objective: To assess the effects of chronic walnut consumption on body weight and
      adiposity in elderly individuals. Methods: The Walnuts and Healthy Aging study is
      a dual-center (Barcelona, Spain and Loma Linda University (LLU)), 2-year
      randomized parallel trial. This report concerns only the LLU cohort. Healthy
      elders (mean age 69 year, 67% women) were randomly assigned to walnut (n = 183)
      or control diets (n = 173). Subjects in the walnut group received packaged
      walnuts (28-56 g/day), equivalent to ~15% of daily energy requirements, to
      incorporate into their habitual diet, while those in the control group abstained
      from walnuts. Adiposity was measured periodically, and data were adjusted for in
      trial changes in self-reported physical activity. Results: After 2 years, body
      weight significantly decreased (p = 0.031), while body fat significantly
      increased (p = 0.0001). However, no significant differences were observed between
      the control and walnut groups regarding body weight (-0.6 kg and -0.4 kg,
      respectively, p = 0.67) or body fat (+0.9% and +1.3%, respectively, p = 0.53).
      Lean body mass, waist circumference, and waist-to-hip ratio remained essentially
      unchanged. Sensitivity analyses were consistent with the findings of primary
      analysis. Conclusion: Our findings indicate that walnuts can be incorporated into
      the daily diet of healthy elders without concern for adverse effects on body
      weight or body composition.

PMID- 30231469
TI  - Thermoelectric Nanocomposite Foams Using Non-Conducting Polymers with Hybrid 1D
      and 2D Nanofillers.
AB  - A facile processing strategy to fabricate thermoelectric (TE) polymer
      nanocomposite foams with non-conducting polymers is reported in this study.
      Multilayered networks of graphene nanoplatelets (GnPs) and multi-walled carbon
      nanotubes (MWCNTs) are deposited on macroporous polyvinylidene fluoride (PVDF)
      foam templates using a layer-by-layer (LBL) assembly technique. The open cellular
      structures of foam templates provide a platform to form segregated 3D networks
      consisting of one-dimensional (1D) and/or two-dimensional (2D) carbon
      nanoparticles. Hybrid nanostructures of GnP and MWCNT networks synergistically
      enhance the material system's electrical conductivity. Furthermore, the polymer
      foam substrates possess high porosity to provide ultra-low thermal conductivity
      without compromising the electrical conductivity of the TE nanocomposites. With
      an extremely low GnP loading (i.e., ~1.5 vol.%), the macroporous PVDF
      nanocomposites exhibit a thermoelectric figure-of-merit of ~10-3. To the best of
      our knowledge, this ZT value is the highest value reported for organic TE
      materials using non-conducting polymers and MWCNT/GnP nanofillers. The proposed
      technique represents an industrially viable approach to fabricate organic TE
      materials with enhanced energy conversion efficiencies. The current study
      demonstrates the potential to develop light-weight, low-cost, and flexible TE
      materials for green energy generation.

PMID- 30231470
TI  - Bioactive Novel Indole Alkaloids and Steroids from Deep Sea-Derived Fungus
      Aspergillus fumigatus SCSIO 41012.
AB  - Two new alkaloids, fumigatosides E (1) and F (2), and a new natural product, 3, 7
      diketo-cephalosporin P1 (6) along with five known compounds (3-5, 7, 8) were
      isolated from deep-sea derived fungal Aspergillus fumigatus SCSIO 41012. Their
      structures were determined by extensive spectroscopic data analysis, including
      1D, 2D nuclear magnetic resonance (NMR) and mass spectrometry (MS), and
      comparison between the calculated and experimental electronic circular dichroism
      (ECD) spectra. In addition, all compounds were tested for antibacterial and
      antifungal inhibitory activities. Compound 1 showed significant antifungal
      activity against Fusarium oxysporum f. sp. momordicae with MIC at 1.56 ug/mL.
      Compound 4 exhibited significant higher activity against S. aureus (16,339 and
      29,213) with MIC values of 1.56 and 0.78 ug/mL, respectively, and compound 2
      exhibited significant activity against A. baumanii ATCC 19606 with a MIC value of
      6.25 ug/mL.

PMID- 30231471
TI  - Influenza Vaccinations for All Pregnant Women? Better Evidence Is Needed.
AB  - Pregnant women are a World Health Organization (WHO) priority group for influenza
      vaccination, but evidence of effectiveness and safety for pregnant women comes
      from observational studies, which are notoriously prone to confounding by
      indication and healthy-vaccinee bias. The latter type of bias leads to an
      overestimation of the effectiveness and safety of the vaccine, which may be what
      occurs in pregnant women. Indeed, better educated women with healthier behaviors
      and who seek better medical care may be more adherent to vaccinations recommended
      by doctors, scientific societies and health authorities. Therefore, it is
      fundamental to obtain information about vaccine effectiveness and safety from
      randomized controlled trials (RCTs). Cochrane reviews have identified only one
      RCT with "low risk of bias". Its results were unclear in terms of maternal,
      perinatal, and infant deaths and hospitalization, and showed a Number Needed to
      Vaccine (NNV) of 55 for mothers, with an excess of local adverse effects. A
      Cochrane review concluded that the inactivated influenza vaccine provides
      pregnant women with uncertain or very limited protection against influenza-like
      illnesses and influenza. Some observational studies have suggested possible
      adverse effects of the inflammation following the vaccination. Consistent with
      the Cochrane reviewers' conclusions, further trials for influenza vaccines with
      appropriate study designs and comparison groups are required before promoting
      universal seasonal influenza vaccinations of pregnant women. Meanwhile,
      vaccination in second to third trimester should be offered while communicating
      the uncertainties that still exist, promoting informed choices. Vaccination in
      the first trimester is debatable and debated. This does not mean leaving women
      defenseless; many other useful behavioral and environmental measures can reduce
      infectious disease.

PMID- 30231472
TI  - From Signal to Image: Enabling Fine-Grained Gesture Recognition with Commercial
      Wi-Fi Devices.
AB  - Gesture recognition acts as a key enabler for user-friendly human-computer
      interfaces (HCI). To bridge the human-computer barrier, numerous efforts have
      been devoted to designing accurate fine-grained gesture recognition systems.
      Recent advances in wireless sensing hold promise for a ubiquitous, non-invasive
      and low-cost system with existing Wi-Fi infrastructures. In this paper, we
      propose DeepNum, which enables fine-grained finger gesture recognition with only
      a pair of commercial Wi-Fi devices. The key insight of DeepNum is to incorporate
      the quintessence of deep learning-based image processing so as to better depict
      the influence induced by subtle finger movements. In particular, we make multiple
      efforts to transfer sensitive Channel State Information (CSI) into depth radio
      images, including antenna selection, gesture segmentation and image construction,
      followed by noisy image purification using high-dimensional relations. To fulfill
      the restrictive size requirements of deep learning model, we propose a novel
      region-selection method to constrain the image size and select qualified regions
      with dominant color and texture features. Finally, a 7-layer Convolutional Neural
      Network (CNN) and SoftMax function are adopted to achieve automatic feature
      extraction and accurate gesture classification. Experimental results demonstrate
      the excellent performance of DeepNum, which recognizes 10 finger gestures with
      overall accuracy of 98% in three typical indoor scenarios.

PMID- 30231474
TI  - Revisiting Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Cancer: Saint or
      Sinner?
AB  - Human neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein present
      in a wide variety of tissues and cell types. NGAL exists as a 25 kDa monomer, a
      46 kDa homodimer (the most abundant form in healthy subjects) and a 130 kDa
      disulfide-linked heterodimer bound to latent matrix metalloproteinase-9.
      Dysregulated expression of NGAL in human malignancies suggests its value as a
      clinical marker. A growing body of evidence is highlighting NGAL's paradoxical
      (i.e., both beneficial and detrimental) effects on cellular processes associated
      with tumor development (proliferation, survival, migration, invasion, and
      multidrug resistance). At least two distinct cell surface receptors are
      identified for NGAL. This review (i) summarizes our current knowledge of NGAL's
      expression profiles in solid tumors and leukemias, and (ii) critically evaluates
      the beneficial and detrimental activities of NGAL having been documented in a
      diverse range of cancer-derived cell lines. A better understanding of the causal
      relationships between NGAL dysregulation and tumor development will require a
      fine analysis of the molecular aspects and biological role(s) of NGAL both in
      primary tumors and at different stages of disease. Having an accurate picture of
      NGAL's contribution to tumor progression is a prerequisite for attempting to
      modulate this protein as a putative therapeutic target.

PMID- 30231473
TI  - The Role of Proton Transport in Gating Current in a Voltage Gated Ion Channel, as
      Shown by Quantum Calculations.
AB  - Over two-thirds of a century ago, Hodgkin and Huxley proposed the existence of
      voltage gated ion channels (VGICs) to carry Na+ and K+ ions across the cell
      membrane to create the nerve impulse, in response to depolarization of the
      membrane. The channels have multiple physiological roles, and play a central role
      in a wide variety of diseases when they malfunction. The first channel structure
      was found by MacKinnon and coworkers in 1998. Subsequently, the structure of a
      number of VGICs was determined in the open (ion conducting) state. This type of
      channel consists of four voltage sensing domains (VSDs), each formed from four
      transmembrane (TM) segments, plus a pore domain through which ions move.
      Understanding the gating mechanism (how the channel opens and closes) requires
      structures. One TM segment (S4) has an arginine in every third position, with one
      such segment per domain. It is usually assumed that these arginines are all
      ionized, and in the resting state are held toward the intracellular side of the
      membrane by voltage across the membrane. They are assumed to move outward
      (extracellular direction) when released by depolarization of this voltage,
      producing a capacitive gating current and opening the channel. We suggest
      alternate interpretations of the evidence that led to these models. Measured
      gating current is the total charge displacement of all atoms in the VSD; we
      propose that the prime, but not sole, contributor is proton motion, not
      displacement of the charges on the arginines of S4. It is known that the VSD can
      conduct protons. Quantum calculations on the Kv1.2 potassium channel VSD show
      how; the key is the amphoteric nature of the arginine side chain, which allows it
      to transfer a proton. This appears to be the first time the arginine side chain
      has had its amphoteric character considered. We have calculated one such proton
      transfer in detail: this proton starts from a tyrosine that can ionize,
      transferring to the NE of the third arginine on S4; that arginine's NH then
      transfers a proton to a glutamate. The backbone remains static. A mutation
      predicted to affect the proton transfer has been qualitatively confirmed
      experimentally, from the change in the gating current-voltage curve. The total
      charge displacement in going from a normal closed potential of -70 mV across the
      membrane to 0 mV (open), is calculated to be approximately consistent with
      measured values, although the error limits on the calculation require caution in
      interpretation.

PMID- 30231475
TI  - Excellent Degradation Performance of a Versatile Phthalic Acid Esters-Degrading
      Bacterium and Catalytic Mechanism of Monoalkyl Phthalate Hydrolase.
AB  - Despites lots of characterized microorganisms that are capable of degrading
      phthalic acid esters (PAEs), there are few isolated strains with high activity
      towards PAEs under a broad range of environmental conditions. In this study,
      Gordonia sp. YC-JH1 had advantages over its counterparts in terms of di(2
      ethylhexyl) phthalate (DEHP) degradation performance. It possessed an excellent
      degradation ability in the range of 20-50  degrees C, pH 5.0-12.0, or 0-8% NaCl
      with the optimal degradation condition 40  degrees C and pH 10.0. Therefore,
      strain YC-JH1 appeared suitable for bioremediation application at various
      conditions. Metabolites analysis revealed that DEHP was sequentially hydrolyzed
      by strain YC-JH1 to mono(2-ethylhexyl) phthalate (MEHP) and phthalic acid (PA).
      The hydrolase MphG1 from strain YC-JH1 hydrolyzed monoethyl phthalate (MEP), mono
      n-butyl phthalate (MBP), mono-n-hexyl phthalate (MHP), and MEHP to PA. According
      to molecular docking and molecular dynamics simulation between MphG1 and
      monoalkyl phthalates (MAPs), some key residues were detected, including the
      catalytic triad (S125-H291-D259) and the residues R126 and F54 potentially
      binding substrates. The mutation of these residues accounted for the reduced
      activity. Together, the mechanism of MphG1 catalyzing MAPs was elucidated, and
      would shed insights into catalytic mechanism of more hydrolases.

PMID- 30231476
TI  - Tipping the Balance: C. albicans Adaptation in Polymicrobial Environments.
AB  - Candida albicans is a pleiomorphic fungus which co-exists with commensal bacteria
      in mucosal and skin sites of mammalian hosts. It is also a major co-isolated
      organism from polymicrobial systemic infections, with high potential for
      morbidity or mortality in immunocompromised patients. Traditionally, resident
      mucosal bacteria have been thought to antagonize C. albicans in its ability to
      colonize or cause infection. However, recent investigations have revealed
      synergistic relationships with certain bacterial species that colonize the same
      mucosal sites with C. albicans. Such relationships broaden the research landscape
      in pathogenesis but also contribute to clinical challenges in the prevention or
      treatment of mucosal candidiasis. This review sheds light on interactions of C.
      albicans and mucosal bacteria, with special emphasis on the effects of the
      resident bacterial microbiota on C. albicans physiology as they relate to its
      adaptation in mucosal sites as a commensal colonizer or as a pathogenic organism.

PMID- 30231478
TI  - Enrichment and Purification of Aucubin from Eucommia ulmoides Ionic Liquid
      Extract Using Macroporous Resins.
AB  - Aiming to address the shortcomings of high-concentration ethanol or methanol
      extraction solutions that need to be diluted and concentrated prior to use in
      conventional macroporous resin adsorption approaches, an efficient approach for
      enrichment and purification of aucubin from the ionic liquid extraction solution
      of samaras of Eucommia ulmoides was proposed. Among the nine kinds of macroporous
      resins investigated, the HPD850 resin was found to be the most suitable.
      Equilibrium adsorption tests were investigated and found to be better fitted by
      the Langmuir isotherm model. After the dynamic tests on a column packed with
      HPD850, the optimum operational conditions were as follows: for the absorption
      process, an initial aucubin concentration of 9.87 mg/L, a sample volume of 13 bed
      volumes (BV), and a flow rate of 2 BV/h; for the water washing process, 5 BV of
      deionized water and a flow rate of 3 BV/h; for the ethanol desorption process, a
      10-80% ethanol volume fraction as the eluent, 2 BV for each ethanol volume
      fraction, and a flow rate of 3 BV/h. The 40-80% ethanol volume fraction eluent
      was collected and concentrated to produce the final products, resulting in an
      aucubin purity and recovery of 79.41% and 72.92%, respectively.

PMID- 30231477
TI  - Affinity Ionic Liquids for Chemoselective Gas Sensing.
AB  - Selective gas sensing is of great importance for applications in health, safety,
      military, industry and environment. Many man-made and naturally occurring
      volatile organic compounds (VOCs) can harmfully affect human health or cause
      impairment to the environment. Gas analysis based on different principles has
      been developed to convert gaseous analytes into readable output signals. However,
      gas sensors such as metal-oxide semiconductors suffer from high operating
      temperatures that are impractical and therefore have limited its applications.
      The cost-effective quartz crystal microbalance (QCM) device represents an
      excellent platform if sensitive, selective and versatile sensing materials were
      available. Recent advances in affinity ionic liquids (AILs) have led them to
      incorporation with QCM to be highly sensitive for real-time detection of target
      gases at ambient temperature. The tailorable functional groups in AIL structures
      allow for chemoselective reaction with target analytes for single digit parts-per
      billion detection on mass-sensitive QCM. This structural diversity makes AILs
      promising for the creation of a library of chemical sensor arrays that could be
      designed to efficiently detect gas mixtures simultaneously as a potential
      electronic in future. This review first provides brief introduction to some
      conventional gas sensing technologies and then delivers the latest results on our
      development of chemoselective AIL-on-QCM methods.

PMID- 30231479
TI  - Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium
      tuberculosis(H37Ra) Model.
AB  - The purpose of the study was to evaluate the antimycobacterial activity and the
      possible action mode of cinnamon bark essential oil and its main constituent
      cinnamaldehyde-against the Mycobacterium tuberculosis ATCC 25177 strain.
      Cinnamaldehyde was proved to be the main bioactive compound responsible for
      mycobacterial growth inhibition and bactericidal effects. The antimycobacterial
      activity of cinnamaldehyde was found to be comparable with that of ethambutol,
      one of the first-line anti-TB antibiotics. The selectivity index determined using
      cell culture studies in vitro showed a high biological potential of
      cinnamaldehyde. In M. tuberculosis cells exposed to cinnamaldehyde the cell
      membrane stress sensing and envelope preserving system are activated.
      Overexpression of clgR gene indicates a threat to the stability of the cell
      membrane and suggests a possible mechanism of action. No synergism was detected
      with the basic set of antibiotics used in tuberculosis treatment: ethambutol,
      isoniazid, streptomycin, rifampicin, and ciprofloxacin.

PMID- 30231480
TI  - Socio-Cultural Reasons and Community Perceptions Regarding Indoor Cooking Using
      Biomass Fuel and Traditional Stoves in Rural Ethiopia: A Qualitative Study.
AB  - Around three billion people in the world and 90% of the rural households in low
      and middle-income countries are exposed to wood smoke with varying exposure
      levels and resulting health risks. We aimed to explore perceptions of the
      community towards indoor cooking and the socio-cultural barriers to bring change
      in Butajira, rural Ethiopia. We conducted a qualitative study involving ten
      separate focus group discussions with purposively selected members of the
      community and two key informant interviews with health extension workers. Content
      analysis was carried out using ATLAS.ti software. Participants reported the use
      of fuel wood and traditional three-stone cook stove to cook food. Economic
      status, lack of commitment, cultural views and concern along with safety and
      security issues were found to be barriers to change from traditional to cleaner
      methods of cooking. The community perceived wood smoke to have effects on their
      eyes and respiratory health, though they culturally viewed it as beneficial for
      postpartum mothers and newborns, avoiding bad smell and insects and in order to
      strengthen the fabric of their houses. Health education at community level is
      essential in order to bring about change in the cultural views and cooking
      behaviors focusing on opening windows and keeping young children away during
      cooking.

PMID- 30231481
TI  - Origanum vulgare Terpenoids Induce Oxidative Stress and Reduce the Feeding
      Activity of Spodoptera littoralis.
AB  - Terpenoids are toxic compounds produced by plants as a defense strategy against
      insect herbivores. We tested the effect of Origanum vulgare terpenoids on the
      generalist herbivore Spodoptera littoralis and the response of the plant to
      herbivory. Terpenoids were analyzed by GC-FID and GC-MS and quantitative gene
      expression (qPCR) was evaluated on selected plant genes involved in both terpene
      biosynthesis. The insect detoxification response to terpenes was evaluated by
      monitoring antioxidant enzymes activity and expression of insect genes involved
      in terpene detoxification. O. vulgare terpenoid biosynthesis and gene expression
      was modulated by S. littoralis feeding. The herbivore-induced increased level of
      terpenoids (particularly carvacrol and p-cymene) interacted with the herbivore by
      decreasing larval survival and growth rate. The assimilation by S. littoralis of
      more than 50% of ingested terpenes correlated with the possible toxic effects of
      O. vulgare terpenoids. In choice test experiments, carvacrol and gamma-terpinene
      mediated the larval feeding preferences, wherease the prolonged feeding on O.
      vulgare terpenoids (particularly on gamma-terpinene) exerted relevant
      antinutritional effects on larvae. S. littoralis was found to react to O. vulgare
      terpenoids by increasing its antioxidant enzymes activities and gene expression,
      although this was not sufficient to sustain the toxicity of O. vulgare
      terpenoids.

PMID- 30231482
TI  - ATP-Induced Increase in Intracellular Calcium Levels and Subsequent Activation of
      mTOR as Regulators of Skeletal Muscle Hypertrophy.
AB  - Intracellular signaling pathways, including the mammalian target of rapamycin
      (mTOR) and the mitogen-activated protein kinase (MAPK) pathway, are activated by
      exercise, and promote skeletal muscle hypertrophy. However, the mechanisms by
      which these pathways are activated by physiological stimulation are not fully
      understood. Here we show that extracellular ATP activates these pathways by
      increasing intracellular Ca2+ levels ([Ca2+]i), and promotes muscle hypertrophy.
      [Ca2+]i in skeletal muscle was transiently increased after exercise. Treatment
      with ATP induced the increase in [Ca2+]i through the P2Y2 receptor/inositol 1,4,5
      trisphosphate receptor pathway, and subsequent activation of mTOR in vitro. In
      addition, the ATP-induced increase in [Ca2+]i coordinately activated Erk1/2, p38
      MAPK and mTOR that upregulated translation of JunB and interleukin-6. ATP also
      induced an increase in [Ca2+]i in isolated soleus muscle fibers, but not in
      extensor digitorum longus muscle fibers. Furthermore, administration of ATP led
      to muscle hypertrophy in an mTOR- and Ca2+-dependent manner in soleus, but not in
      plantaris muscle, suggesting that ATP specifically regulated [Ca2+]i in slow
      muscles. These findings suggest that ATP and [Ca2+]i are important mediators that
      convert mechanical stimulation into the activation of intracellular signaling
      pathways, and point to the P2Y receptor as a therapeutic target for treating
      muscle atrophy.

PMID- 30231483
TI  - Stress-Induced Mucus Secretion and Its Composition by a Combination of Proteomics
      and Metabolomics of the Jellyfish Aurelia coerulea.
AB  - BACKGROUND: Jellyfish respond quickly to external stress that stimulates mucus
      secretion as a defense. Neither the composition of secreted mucus nor the process
      of secretion are well understood. METHODS: Aurelia coerulea jellyfish were
      stimulated by removing them from environmental seawater. Secreted mucus and
      tissue samples were then collected within 60 min, and analyzed by a combination
      of proteomics and metabolomics using liquid chromatography coupled with tandem
      mass spectrometry (LC-MS/MS) and ultra-performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS),
      respectively. RESULTS: Two phases of sample collection displayed a quick decrease
      in volume, followed by a gradual increase. A total of 2421 and 1208 proteins were
      identified in tissue homogenate and secreted mucus, respectively. Gene Ontology
      (GO) analysis showed that the mucus-enriched proteins are mainly located in
      extracellular or membrane-associated regions, while the tissue-enriched proteins
      are distributed throughout intracellular compartments. Tryptamine, among 16
      different metabolites, increased with the largest-fold change value of 7.8 in
      mucus, which is consistent with its involvement in the Kyoto Encyclopedia of
      Genes and Genomes (KEGG) pathway 'tryptophan metabolism'. We identified 11
      metalloproteinases, four serpins, three superoxide dismutases and three
      complements, and their presence was speculated to be related to self-protective
      defense. CONCLUSIONS: Our results provide a composition profile of proteins and
      metabolites in stress-induced mucus and tissue homogenate of A. coerulea. This
      provides insight for the ongoing endeavors to discover novel bioactive compounds.
      The large increase of tryptamine in mucus may indicate a strong stress response
      when jellyfish were taken out of seawater and the active self-protective
      components such as enzymes, serpins and complements potentially play a key role
      in innate immunity of jellyfish.

PMID- 30231484
TI  - Repressed Exercise-Induced Hepcidin Levels after Danggui Buxue Tang
      Supplementation in Male Recreational Runners.
AB  - This study was to investigate the protective and recovery effects of Danggui
      Buxue Tang (DBT) supplementation on exercise performance, hepcidin, iron status,
      and other related biochemical parameters after being challenged by a single bout
      of intense aerobic exercise. A total of 36 recreationally active males were pair
      matched and randomly assigned to receive DBT or a placebo for 11 days, while
      using clusters based on their aerobic capacities. On the eighth day of the
      supplementation, the participants performed a 13-km run with maximal effort.
      Blood and urine samples were collected and analysed before treatment (Pre-Tre)
      and immediately after (Post-Ex), 24 h after (24-h Rec), and 72 h after (72-h Rec)
      the run. DBT supplementation dramatically shortened the finish times by 14.0%
      (12.3 min) when compared with that in the placebo group. Significant group * time
      effects were observed in serum hepcidin and iron levels. DBT supplementation
      repressed hepcidin levels at Post-Ex and 24-h Rec, thereby causing a significant
      increase in iron levels by 63.3% and 31.4% at Post-Ex and 72-h Rec, respectively.
      However, DBT supplementation had no significant anti-inflammatory or haemolysis
      preventative effects. Short-term DBT supplementation shortened the running time
      and repressed exercise-induced hepcidin levels, thereby boosting iron levels and
      accelerating iron homeostasis during recovery.

PMID- 30231485
TI  - Brucella spp. at the Wildlife-Livestock Interface: An Evolutionary Trajectory
      through a Livestock-to-Wildlife "Host Jump"?
AB  - Brucella infections in wildlife have gained a lot of interest from the scientific
      community and different stakeholders. These interests are often different and
      sometimes conflicting. As a result, different management perspectives and aims
      have been implemented (One Health, public health, veterinary public health,
      maintenance of a brucellosis free status in livestock, sustainable wildlife
      harvesting by hunters, wildlife and environmental health). When addressing
      Brucella infection in wildlife, the most important features of Brucella infection
      should be considered and the following questions need to be answered: (1) Is
      Brucella infection a result of a spillover from livestock or is it a sustainable
      infection in one or more wildlife host species? (2) Did the epidemiological
      situation of Brucella infection in wildlife change over time and, if so, what are
      the main drivers of change and does it impact the wildlife population dynamics?
      (3) Does Brucella infection in wildlife represent a reservoir of Brucella strains
      for livestock? (4) Is Brucella infection in wildlife of zoonotic concern? These
      questions point to the fundamental biological question of how animal (domestic
      and wildlife)/Brucella spp. partnerships are established. Will we be able to
      decipher an evolutionary trajectory through a livestock-to-wildlife "host jump"?
      Whole genome sequencing and new "omics" techniques will help in deciphering the
      molecular basis of Brucella host preference and open new avenues in brucellosis
      management aimed at preventing opportunities for Brucella host jumps.

PMID- 30231486
TI  - Direct Transamidation Reactions: Mechanism and Recent Advances.
AB  - Amides are undeniably some of the most important compounds in Nature and the
      chemical industry, being present in biomolecules, materials, pharmaceuticals and
      many other substances. Unfortunately, the traditional synthesis of amides suffers
      from some important drawbacks, principally the use of stoichiometric activators
      or the need to use highly reactive carboxylic acid derivatives. In recent years,
      the transamidation reaction has emerged as a valuable alternative to prepare
      amides. The reactivity of amides makes their direct reaction with nitrogen
      nucleophiles difficult; thus, the direct transamidation reaction needs a catalyst
      in order to activate the amide moiety and to promote the completion of the
      reaction because equilibrium is established. In this review, we present research
      on direct transamidation reactions ranging from studies of the mechanism to the
      recent developments of more applicable and versatile methodologies, emphasizing
      those reactions involving activation with metal catalysts.

PMID- 30231488
TI  - Acoustic Emissions in 3D Printed Parts under Mode I Delamination Test.
AB  - This paper applies an innovative approach based on the acoustic emission
      technique to monitor the delamination process of 3D parts. Fused deposition
      modelling (FDM) is currently one of the most widespread techniques for additive
      manufacturing of a solid object from a computer model. Fundamentally, this
      process is based on a layer-by-layer deposition of a fused filament. The FDM
      technique has evolved to the point where it can now be proposed, not only as a
      prototyping technique, but also as one applicable to direct manufacturing.
      Nonetheless, a deeper comprehension of mechanical behavior and its dependence on
      process parameters must include the determination of material properties as a
      function of the service load. In this work, the effects of extrusion temperature
      on inter-layer cohesion are studied using a method employing a double cantilever
      beam (DCB). The ASTM D5528 standard was used to determine the delamination
      energy, GI. In addition, the acoustic emission technique was employed to follow
      the delamination process during testing. Finally, a Charge-Coupled Device (CCD)
      camera and a calibrated grid was employed to evaluate crack propagation during
      testing.

PMID- 30231487
TI  - lncRNA NTT/PBOV1 Axis Promotes Monocyte Differentiation and Is Elevated in
      Rheumatoid Arthritis.
AB  - Monocytes/macrophages are important in orchestrating inflammatory responses.
      However, knowledge of the long noncoding RNA (lncRNA) regulation of monocytic
      cell differentiation and diseases remains limited. We aimed to elucidate the role
      of the 17 kb lncRNA noncoding transcript in T cells (NTT) in monocyte functions.
      Knockdown and chromatin immunoprecipitation (ChIP) assays in THP-1 cells (human
      monocytic leukemia cell line) revealed that NTT is regulated by the monocyte key
      transcription factor C/EBPbeta and that it binds to the promoter of nearby gene
      PBOV1 via hnRNP-U. Overexpression of PBOV1 in THP-1 cells resulted in cell cycle
      G1 arrest, differentiation into macrophages, a marked increase in IL-10 and
      CXCL10 mRNA levels, and upregulation of the costimulatory molecules. In contrast
      to the downregulated NTT observed in lipopolysaccharide (LPS)-treated THP-1
      cells, the C/EBPbeta/NTT/PBOV1 axis was found to be hyperactivated in peripheral
      blood mononuclear cells (PBMCs) of first-time diagnosed untreated early
      rheumatoid arthritis (RA) patients, and their gene expression levels decreased
      markedly after treatment. Higher initial C/EBPbeta/NTT/PBOV1 expression levels
      were associated with a trend of higher disease activity DAS28 scores. In
      conclusion, our study suggests that the lncRNA NTT is a regulator of inflammation
      in monocytes, and its activation participates in monocyte/macrophage
      differentiation and the pathogenesis of RA.

PMID- 30231489
TI  - Surface Hydrophobicity and Functional Properties of Citric Acid Cross-Linked Whey
      Protein Isolate: The Impact of pH and Concentration of Citric Acid.
AB  - The effects of citric acid-mediated cross-linking under non-acidic conditions on
      the surface hydrophobicity, solubility, emulsifying, and foaming properties of
      whey protein isolate (WPI) were investigated. In this research, citric acid
      mediated cross-linking could not only increase the surface hydrophobicity of whey
      proteins at pH 7.0 and 8.0, but it also improved its emulsifying and foaming
      properties. The emulsifying activity and foaming ability of WPI reached a maximum
      under the condition of 1% citric acid and pH 7.0. However, the solubility of WPI
      CA gradually decreased with pH and the content of citric acid increased.
      Therefore, the cross-linking mediated by citric acid under non-acidic aqueous
      conditions, markedly altered the surface hydrophobicity and enhanced emulsifying
      and foaming properties of WPI.

PMID- 30231490
TI  - Genome-Wide Identification, Molecular Evolution, and Expression Divergence of
      Aluminum-Activated Malate Transporters in Apples.
AB  - Aluminum-activated malate transporters (ALMTs) play an important role in aluminum
      tolerance, stomatal opening, and fruit acidity in plants. However, the
      evolutionary pattern of the ALMT gene family in apples remains relatively
      unknown. In this study, a total of 25 MdALMT genes were identified from the apple
      reference genome of the "Golden Delicious" doubled-haploid tree (GDDH13). The
      physiological and biochemical properties, gene structure, and conserved motifs of
      MdALMT genes were examined. Chromosome location and gene-duplication analysis
      indicated that whole-genome duplication/segmental duplication played an important
      role in the expansion of the MdALMT gene family. The Ka/Ks ratio of duplicated
      MdALMT genes showed that members of this family have undergone strong purifying
      selection. Through exploration of the phylogenetic relationships, seven subgroups
      were classified, and higher old gene duplication frequency and significantly
      different evolutionary rates of the ALMT gene families were detected. In
      addition, the functional divergence of ALMT genes occurred during the
      evolutionary process of Rosaceae species. Furthermore, the functional divergence
      of MdALMT genes was confirmed by expression discrepancy and different subcellular
      localizations. This study provides the foundation to better understand the
      molecular evolution of MdALMT genes and further facilitate functional analysis to
      unravel their exact role in apples.

PMID- 30231492
TI  - Simultaneous Localization and Map Change Update for the High Definition Map-Based
      Autonomous Driving Car.
AB  - High Definition (HD) maps are becoming key elements of the autonomous driving
      because they can provide information about the surrounding environment of the
      autonomous car without being affected by the real-time perception limit. To
      provide the most recent environmental information to the autonomous driving
      system, the HD map must maintain up-to-date data by updating changes in the real
      world. This paper presents a simultaneous localization and map change update
      (SLAMCU) algorithm to detect and update the HD map changes. A Dempster-Shafer
      evidence theory is applied to infer the HD map changes based on the evaluation of
      the HD map feature existence. A Rao-Blackwellized particle filter (RBPF) approach
      is used to concurrently estimate the vehicle position and update the new map
      state. The detected and updated map changes by the SLAMCU are reported to the HD
      map database in order to reflect the changes to the HD map and share the changing
      information with the other autonomous cars. The SLAMCU was evaluated through
      experiments using the HD map of traffic signs in the real traffic conditions.

PMID- 30231491
TI  - The Dynamic Changes of Gut Microbiota in Muc2 Deficient Mice.
AB  - Gut dysbiosis is associated with colitis-associated colorectal carcinogenesis,
      and the genetic deficiency of the Muc2 gene causes spontaneous development of
      colitis and colorectal cancer. Whether there are changes of gut microbiota and a
      linkage between the changes of microbiota and intestinal pathology in Muc2-/-
      mice are unclear. Muc2-/- and Muc2+/+ mice were generated by backcrossing from
      Muc2+/- mice, and the fecal samples were collected at different dates (48th,
      98th, 118th, 138th, and 178th day). Gut microbiota were analyzed by high
      throughput sequencing with the universal 16S rRNA primers (V3-V5 region). All
      mice were sacrificed at day 178 to collect colonic tissue and epithelial cells
      for the analysis of histopathology and inflammatory cytokines. On the 178th day,
      Muc2-/- mice developed colorectal chronic colitis, hyperplasia, adenomas and
      adenocarcinomas, and inflammatory cytokines (e.g., cyclooxygenase 2 (COX-2),
      interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta
      (IL-1beta), i-kappa-B-kinase beta (IKKbeta)) were significantly increased in
      colonic epithelial cells of Muc2-/- mice. In general, structural segregation of
      gut microbiota was observed throughout the experimental time points between the
      Muc2-/- and Muc2+/+ mice. Impressively, in Muc2-/- mice, Alpha diversities
      reflected by Shannon and Chao indexes were higher, the phylum of Firmicutes was
      enriched and Bacteroidetes was decreased, and Desulfovibrio, Escherichia,
      Akkermansia, Turicibacter, and Erysipelotrichaceae were significantly increased,
      but Lactobacilli and Lachnospiraceae were significantly decreased. Moreover, the
      abundance of Ruminococcaceae and butyrate-producing bacteria was significantly
      higher in the Muc2-/- mice. There were significant differences of gut microbiota
      between Muc2-/- and Muc2+/+ mice. The dynamic changes of microbiota might
      contribute to the development of colitis and colitis-associated colorectal
      carcinogenesis. Therefore, this study revealed specific functional bacteria in
      the development of colitis and colitis-associated colorectal carcinogenesis,
      which will benefit the development of preventive and therapeutic strategies for
      chronic inflammation and its malignant transformation.

PMID- 30231495
TI  - Perovskite Thin Film Consisting with One-Dimensional Nanowires.
AB  - Organic-inorganic hybrid perovskite solar cells had attracted extensive attention
      due to their high-power conversion efficiency and low cost. The morphology and
      structure of the light absorption layer are crucially important for the device
      performance. The one-dimensional or two dimensional nano-structure perovskite
      material exhibits better optical and electrical properties than three-dimensional
      bulk perovskite. In this article, the perovskite CH3NH3PbI3 thin films with one
      dimensional nanowires structure were prepared while using the solution method
      with N,N-Dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) mixed solvent
      under atmospheric environment. During the perovskite thin films growth, the DMSO
      solvent as a structure directing agent played a guiding role in the formation of
      nanowires. The effects of DMSO solvent added ratio on the perovskite thin film
      structure, morphology, optical properties, and the device performance were
      studied. By changing the ratio of DMSO solvent added can effectively adjust the
      orientation order and optical properties of the nanowires perovskite thin films.
      The results showed that the best ratio of DMSO solvent added in the mixed solvent
      was 10%. The high order orientation of the perovskite thin film with nanowires
      forest was obtained. It showed the high optical absorption and electrical
      properties. The perovskite absorption layer presents ordered and dispersed
      nanowires forest; the device power conversation efficiency is increased by 50%
      when compared with the perovskite layer presents disordered nanowires.

PMID- 30231493
TI  - Methodological Approaches to Study Extracellular Vesicle miRNAs in Epstein-Barr
      Virus-Associated Cancers.
AB  - Epstein Barr-virus (EBV) was the first virus identified to be associated with
      human cancer in 1964 and is found ubiquitously throughout the world's population.
      It is now established that EBV contributes to the development and progression of
      multiple human cancers of both lymphoid and epithelial cell origins. EBV encoded
      miRNAs play an important role in tumor proliferation, angiogenesis, immune
      escape, tissue invasion, and metastasis. Recently, EBV miRNAs have been found to
      be released from infected cancer cells in extracellular vesicles (EVs) and
      regulate gene expression in neighboring uninfected cells present in the tumor
      microenvironment and possibly at distal sites. As EVs are abundant in many
      biological fluids, the viral and cellular miRNAs present within EBV-modified EVs
      may serve as noninvasion markers for cancer diagnosis and prognosis. In this
      review, we discuss recent advances in EV isolation and miRNA detection, and
      provide a complete workflow for EV purification from plasma and deep-sequencing
      for biomarker discovery.

PMID- 30231497
TI  - Evaluation of Metal Oxide Surface Catalysts for the Electrochemical Activation of
      Amino Acids.
AB  - Electrochemical detection of amino acids is important due to their correlation
      with certain diseases; however, most amino acids require a catalyst to
      electrochemically activate. One common catalyst for electrochemical detection of
      amino acids are metal oxides. Metal oxide nanoparticles were electrodeposited
      onto glassy carbon and platinum working electrodes. Cyclic voltammetry (CV)
      experiments in a flow cell were performed to evaluate the sensors' ability to
      detect arginine, alanine, serine, and valine at micromolar and nanomolar
      concentrations as high as 4 mM. Solutions were prepared in phosphate buffer
      saline (PBS) and then 100 mM NaOH. Specifically, NiO surfaces were responsive to
      amino acids but variable, especially when exposed to arginine. Polarization
      resistance experiments and scanning electron microscopy (SEM) and energy
      dispersive X-ray spectroscopy (EDS) data indicated that arginine accelerated the
      corrosion of the NiO catalyst through the formation of a Schiff base complex.

PMID- 30231494
TI  - Relationship of Time-Activity-Adjusted Particle Number Concentration with Blood
      Pressure.
AB  - Emerging evidence suggests long-term exposure to ultrafine particulate matter
      (UFP, aerodynamic diameter < 0.1 um) is associated with adverse cardiovascular
      outcomes. We investigated whether annual average UFP exposure was associated with
      measured systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse
      pressure (PP), and hypertension prevalence among 409 adults participating in the
      cross-sectional Community Assessment of Freeway Exposure and Health (CAFEH)
      study. We used measurements of particle number concentration (PNC, a proxy for
      UFP) obtained from mobile monitoring campaigns in three near-highway and three
      urban background areas in and near Boston, Massachusetts to develop PNC
      regression models (20-m spatial and hourly temporal resolution). Individual
      modeled estimates were adjusted for time spent in different micro-environments
      (time-activity-adjusted PNC, TAA-PNC). Mean TAA-PNC was 22,000 particles/cm3 (sd
      = 6500). In linear models (logistic for hypertension) adjusted for the minimally
      sufficient set of covariates indicated by a directed acyclic graph (DAG), we
      found positive, non-significant associations between natural log-transformed TAA
      PNC and SBP (beta = 5.23, 95%CI: -0.68, 11.14 mmHg), PP (beta = 4.27, 95%CI: 
      0.79, 9.32 mmHg), and hypertension (OR = 1.81, 95%CI: 0.94, 3.48), but not DBP
      (beta = 0.96, 95%CI: -2.08, 4.00 mmHg). Associations were stronger among non
      Hispanic white participants and among diabetics in analyses stratified by
      race/ethnicity and, separately, by health status.

PMID- 30231496
TI  - The Functions of the Mammalian Methionine Sulfoxide Reductase System and Related
      Diseases.
AB  - This review article describes and discusses the current knowledge on the general
      role of the methionine sulfoxide reductase (MSR) system and the particular role
      of MSR type A (MSRA) in mammals. A powerful tool to investigate the contribution
      of MSRA to molecular processes within a mammalian system/organism is the MSRA
      knockout. The deficiency of MSRA in this mouse model provides hints and evidence
      for this enzyme function in health and disease. Accordingly, the potential
      involvement of MSRA in the processes leading to neurodegenerative diseases,
      neurological disorders, cystic fibrosis, cancer, and hearing loss will be
      deliberated and evaluated.

PMID- 30231498
TI  - A Critical Role for HlgA in Staphylococcus aureus Pathogenesis Revealed by A
      Switch in the SaeRS Two-Component Regulatory System.
AB  - Cytolytic pore-forming toxins including alpha hemolysin (Hla) and bicomponent
      leukotoxins play an important role in the pathogenesis of Staphylococcus aureus.
      These toxins kill the polymorphonuclear phagocytes (PMNs), disrupt epithelial and
      endothelial barriers, and lyse erythrocytes to provide iron for bacterial growth.
      The expression of these toxins is regulated by the two-component sensing systems
      Sae and Agr. Here, we report that a point mutation (L18P) in SaeS, the histidine
      kinase sensor of the Sae system, renders the S. aureus Newman hemolytic activity
      fully independent of Hla and drastically increases the PMN lytic activity.
      Furthermore, this Hla-independent activity, unlike Hla itself, can lyse human
      erythrocytes. The Hla-independent activity towards human erythrocytes was also
      evident in USA300, however, under strict agr control. Gene knockout studies
      revealed that this Hla-independent Sae-regulated activity was entirely dependent
      on gamma hemolysin A subunit (HlgA). In contrast, hemolytic activity of Newman
      towards human erythrocytes from HlgAB resistant donors was completely dependent
      on agr. The culture supernatant from Newman S. aureus could be neutralized by
      antisera against two vaccine candidates based on LukS and LukF subunits of Panton
      Valentine leukocidin but not by an anti-Hla neutralizing antibody. These findings
      display the complex involvement of Sae and Agr systems in regulating the
      virulence of S. aureus and have important implications for vaccine and
      immunotherapeutics development for S. aureus disease in humans.

PMID- 30231500
TI  - Effects of Interfacial Passivation on the Electrical Performance, Stability, and
      Contact Properties of Solution Process Based ZnO Thin Film Transistors.
AB  - This paper reports low temperature solution processed ZnO thin film transistors
      (TFTs), and the effects of interfacial passivation of a 4-chlorobenzoic acid
      (PCBA) layer on device performance. It was found that the ZnO TFTs with PCBA
      interfacial modification layers exhibited a higher electron mobility of 4.50 cm2
      V-1 s-1 compared to the pristine ZnO TFTs with a charge carrier mobility of 2.70
      cm2 V-1 s-1. Moreover, the ZnO TFTs with interfacial modification layers could
      significantly improve device shelf-life stability and bias stress stability
      compared to the pristine ZnO TFTs. Most importantly, interfacial modification
      layers could also decrease the contact potential barrier between the source/drain
      electrodes and the ZnO films when using high work-function metals such as Ag and
      Au. These results indicate that high performance TFTs can be obtained with a low
      temperature solution process with interfacial modification layers, which strongly
      implies further potential for their applications.

PMID- 30231499
TI  - Deep Learning in Drug Discovery and Medicine; Scratching the Surface.
AB  - The practice of medicine is ever evolving. Diagnosing disease, which is often the
      first step in a cure, has seen a sea change from the discerning hands of the
      neighborhood physician to the use of sophisticated machines to use of information
      gleaned from biomarkers obtained by the most minimally invasive of means. The
      last 100 or so years have borne witness to the enormous success story of
      allopathy, a practice that found favor over earlier practices of medical
      purgatory and homeopathy. Nevertheless, failures of this approach coupled with
      the omics and bioinformatics revolution spurred precision medicine, a platform
      wherein the molecular profile of an individual patient drives the selection of
      therapy. Indeed, precision medicine-based therapies that first found their place
      in oncology are rapidly finding uses in autoimmune, renal and other diseases.
      More recently a new renaissance that is shaping everyday life is making its way
      into healthcare. Drug discovery and medicine that started with Ayurveda in India
      are now benefiting from an altogether different artificial intelligence (AI)-one
      which is automating the invention of new chemical entities and the mining of
      large databases in health-privacy-protected vaults. Indeed, disciplines as
      diverse as language, neurophysiology, chemistry, toxicology, biostatistics,
      medicine and computing have come together to harness algorithms based on transfer
      learning and recurrent neural networks to design novel drug candidates, a priori
      inform on their safety, metabolism and clearance, and engineer their delivery but
      only on demand, all the while cataloging and comparing omics signatures across
      traditionally classified diseases to enable basket treatment strategies. This
      review highlights inroads made and being made in directed-drug design and
      molecular therapy.

PMID- 30231501
TI  - Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone
      Hydrolase and V153H Mutant.
AB  - Zearalenone hydrolase (ZHD) is the only reported alpha/beta-hydrolase that can
      detoxify zearalenone (ZEN). ZHD has demonstrated its potential as a treatment for
      ZEN contamination that will not result in damage to cereal crops. Recent
      researches have shown that the V153H mutant ZHD increased the specific activity
      against alpha-ZOL, but decreased its specific activity to beta-ZOL. To understand
      whyV153H mutation showed catalytic specificity for alpha-ZOL, four molecular
      dynamics simulations combining with protein network analysis for wild type ZHD
      alpha-ZOL, ZHD beta-ZOL, V153H alpha-ZOL, and V153H beta-ZOL complexes were
      performed using Gromacs software. Our theoretical results indicated that the
      V153H mutant could cause a conformational switch at the cap domain (residues
      Gly161-Thr190) to affect the relative position catalytic residue (H242). Protein
      network analysis illustrated that the V153H mutation enhanced the communication
      with the whole protein and residues with high betweenness in the four complexes,
      which were primarily assembled in the cap domain and residues Met241 to Tyr245
      regions. In addition, the existence of alpha-ZOL binding to V153H mutation
      enlarged the distance from the OAE atom in alpha-ZOL to the NE2 atom in His242,
      which prompted the side chain of H242 to the position with catalytic activity,
      thereby increasing the activity of V153H on the alpha-ZOL. Furthermore, alpha-ZOL
      could easily form a right attack angle and attack distance in the ZHD and alpha
      ZOL complex to guarantee catalytic reaction. The alanine scanning results
      indicated that modifications of the residues in the cap domain produced
      significant changes in the binding affinity for alpha-ZOL and beta-ZOL. Our
      results may provide useful theoretical evidence for the mechanism underlying the
      catalytic specificity of ZHD.

PMID- 30231502
TI  - Bioactive Composition, Antioxidant Activity, and Anticancer Potential of Freeze
      Dried Extracts from Defatted Gac (Momordica cochinchinensis Spreng) Seeds.
AB  - Background: Gac (Momordica cochinchinensis Spreng) seeds have long been used in
      traditional medicine as a remedy for numerous conditions due to a range of
      bioactive compounds. This study investigated the solvent extraction of compounds
      that could be responsible for antioxidant activity and anticancer potential.
      Methods: Defatted Gac seed kernel powder was extracted with different solvents:
      100% water, 50% methanol:water, 70% ethanol:water, water saturated butanol, 100%
      methanol, and 100% ethanol. Trypsin inhibitors, saponins, phenolics, and
      antioxidant activity using the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic
      acid) diammonium salt (ABTS), the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the
      ferric reducing antioxidant power (FRAP) assays; and anticancer potential against
      two melanoma cancer cell lines (MM418C1 and D24) were analysed to determine the
      best extraction solvents. Results: Water was best for extracting trypsin
      inhibitors (581.4 +/- 18.5 mg trypsin/mg) and reducing the viability of MM418C1
      and D24 melanoma cells (75.5 +/- 1.3 and 66.9 +/- 2.2%, respectively); the
      anticancer potential against the MM418C1 cells was highly correlated with trypsin
      inhibitors (r = 0.92, p < 0.05), but there was no correlation between anticancer
      potential and antioxidant activity. The water saturated butanol had the highest
      saponins (71.8 +/- 4.31 mg aescin equivalents/g), phenolic compounds (20.4 +/-
      0.86 mg gallic acid equivalents/g), and antioxidant activity, but these measures
      were not related to anticancer potential. Conclusions: Water yielded a Gac seed
      extract, rich in trypsin inhibitors, which had high anticancer potential against
      two melanoma cell lines.

PMID- 30231503
TI  - Phenolic Compounds in Organic and Aqueous Extracts from Acacia farnesiana Pods
      Analyzed by ULPS-ESI-Q-oa/TOF-MS. In Vitro Antioxidant Activity and Anti
      Inflammatory Response in CD-1 Mice.
AB  - BACKGROUND: Acacia farnesiana (AF) pods have been traditionally used to treat
      dyspepsia, diarrhea and topically for dermal inflammation. Main objectives: (1)
      investigate the antioxidant activity and protection against oxidative-induced
      damage of six extracts from AF pods and (2) their capacity to curb the
      inflammation process as well as to down-regulate the pro-inflammatory mediators.
      METHODS: Five organic extracts (chloroformic, hexanic, ketonic, methanolic,
      methanolic:aqueous and one aqueous extract) were obtained and analyzed by UPLC
      ESI-Q-oa/TOF-MS. Antioxidant activity (DPPH*, ORAC and FRAP assays) and lipid
      peroxidation (TBARS assay) were performed. Assessment of anti-inflammatory
      properties was made by the ear edema induced model in CD-1 mice and MPO activity
      assay. Likewise, histological analysis, IL-1beta, IL-6, IL-10, TNF-alpha, COX
      measurements plus nitrite and immunohistochemistry analysis were carried out.
      RESULTS: Methyl gallate, gallic acid, galloyl glucose isomer 1, galloyl glucose
      isomer 2, galloyl glucose isomer 3, digalloyl glucose isomer 1, digalloyl glucose
      isomer 2, digalloyl glucose isomer 3, digalloyl glucose isomer 4, hydroxytyrosol
      acetate, quinic acid, and caffeoylmalic acid were identified. Both organic and
      aqueous extracts displayed antioxidant activity. All extracts exhibited a
      positive effect on the interleukins, COX and immunohistochemistry assays.
      CONCLUSION: All AF pod extracts can be effective as antioxidant and topical anti
      inflammatory agents.

PMID- 30231505
TI  - Lactobacillus rhamnosus GG in the Primary Prevention of Eczema in Children: A
      Systematic Review and Meta-Analysis.
AB  - Current guidelines recommend the use of probiotics to reduce the risk of eczema.
      It remains unclear which strain(s) to use. We systematically evaluated data on
      the efficacy of Lactobacillus rhamnosus GG (LGG) supplementation prenatally
      and/or postnatally for the primary prevention of eczema. The Cochrane Library,
      MEDLINE, and EMBASE databases were searched up to August 2018, with no language
      restrictions, for systematic reviews of randomized controlled trials (RCTs) and
      RCTs published afterwards. The primary outcome was eczema. For dichotomous
      outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A
      random-effects model was used to pool data. Heterogeneity was explored using the
      I2 statistics. The GRADE criteria were used to assess the overall quality of
      evidence supporting the primary outcome. Seven publications reporting 5 RCTs (889
      participants) were included. High to moderate certainty in the body of evidence
      suggests that LGG supplementation (regardless of the timing of administration)
      did not reduce the risk of eczema. There was also no consistent effect on other
      allergic outcomes. This meta-analysis shows that LGG was ineffective in reducing
      eczema. It does not support the general recommendation to use probiotics for
      preventing eczema, unless specific strains would be indicated.

PMID- 30231504
TI  - Preclinical Evaluation of [68Ga]Ga-DFO-ZEGFR:2377: A Promising Affibody-Based
      Probe for Noninvasive PET Imaging of EGFR Expression in Tumors.
AB  - : Radionuclide imaging of epidermal growth factor receptor (EGFR) expression in
      tumors may stratify patients for EGFR-targeting therapies and predict response or
      resistance to certain treatments. Affibody molecules, which are nonimmunoglobulin
      scaffold proteins, have a high potential as probes for molecular imaging. In this
      study, maleimido derivative of desferrioxamine B (DFO) chelator was site
      specifically coupled to the C-terminal cysteine of the anti-EGFR affibody
      molecule ZEGFR:2377, and the DFO-ZEGFR:2377 conjugate was labeled with the
      generator-produced positron-emitting radionuclide 68Ga. Stability, specificity of
      binding to EGFR-expressing cells, and processing of [68Ga]Ga-DFO-ZEGFR:2377 by
      cancer cells after binding were evaluated in vitro. In vivo studies were
      performed in nude mice bearing human EGFR-expressing A431 epidermoid cancer
      xenografts. The biodistribution of [68Ga]Ga-DFO-ZEGFR:2377 was directly compared
      with the biodistribution of [89Zr]Zr-DFO-ZEGFR:2377. DFO-ZEGFR: 2377 was
      efficiently (isolated yield of 73 +/- 3%) and stably labeled with 68Ga. Binding
      of [68Ga]Ga-DFO-ZEGFR:2377 to EGFR-expressing cells in vitro was receptor
      specific and proportional to the EGFR expression level. In vivo saturation
      experiment demonstrated EGFR-specific accumulation of [68Ga]Ga-DFO-ZEGFR:2377 in
      A431 xenografts. Compared to [89Zr]Zr-DFO-ZEGFR:2377, [68Ga]Ga-DFO-ZEGFR:2377
      demonstrated significantly (p < 0.05) higher uptake in tumors and lower uptake in
      spleen and bones. This resulted in significantly higher tumor-to-organ ratios for
      [68Ga]Ga-DFO-ZEGFR:2377. In conclusion, [68Ga]Ga-DFO-ZEGFR:2377 is a promising
      probe for imaging of EGFR expression.

PMID- 30231507
TI  - "We Always Hurt the Things We Love"-Unnoticed Abuse of Companion Animals.
AB  - Despite the fact that companion animals enjoy the status of "members of the
      family" in contemporary society, there are numerous diseases affecting the
      longevity of these animals and their quality of life. Some of the most pervasive
      and damaging problems accrue to pedigreed animals whose genetic lines contain
      many major and severe diseases which are detrimental to both the quality and
      length of life. If one considers the most popular dog breeds in the United
      States, the top 10 include the Labrador Retriever, German Shepherd, Golden
      Retriever, French Bulldog, Beagle, Poodle, Rottweiler, Yorkshire Terrier, and
      German Shorthaired Pointer. Some idea of the pervasiveness of genetic defects
      across breeds can be gleaned from a recent book detailing genetic predisposition
      to disease. The book contains 93 pages of references. The list of diseases for
      the most popular dog, the Labrador Retriever, is 6.25 pages long. Yet, despite
      the tragic consequences of such diseases in animals regarded as beloved family
      members, breed standards associated with these diseases remain unchanged. This
      represents a major tragedy to which insufficient attention is paid. The point of
      this paper is to show that even as dogs have increasingly become viewed as
      "members of the family", this status is belied by the proliferation of genetic
      diseases perpetuated by breed standards.

PMID- 30231506
TI  - A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for
      Designing Novel Drugs.
AB  - A combined in silico method was developed to predict potential protein targets
      that are involved in cardiotoxicity induced by aconitine alkaloids and to study
      the quantitative structure-toxicity relationship (QSTR) of these compounds. For
      the prediction research, a Protein-Protein Interaction (PPI) network was built
      from the extraction of useful information about protein interactions connected
      with aconitine cardiotoxicity, based on nearly a decade of literature and the
      STRING database. The software Cytoscape and the PharmMapper server were utilized
      to screen for essential proteins in the constructed network. The Calcium
      Calmodulin-Dependent Protein Kinase II alpha (CAMK2A) and gamma (CAMK2G) were
      identified as potential targets. To obtain a deeper insight on the relationship
      between the toxicity and the structure of aconitine alkaloids, the present study
      utilized QSAR models built in Sybyl software that possess internal robustness and
      external high predictions. The molecular dynamics simulation carried out here
      have demonstrated that aconitine alkaloids possess binding stability for the
      receptor CAMK2G. In conclusion, this comprehensive method will serve as a tool
      for following a structural modification of the aconitine alkaloids and lead to a
      better insight into the cardiotoxicity induced by the compounds that have similar
      structures to its derivatives.

PMID- 30231509
TI  - Multi-Robot Cyber Physical System for Sensing Environmental Variables of
      Transmission Line.
AB  - The normal operation of a power grid largely depends on the effective monitoring
      and maintenance of transmission lines, which is a process that has many
      challenges. The traditional method of the manual or remote inspection of
      transmission lines is time-consuming, laborious, and inefficient. To address this
      problem, a novel method has been proposed for the Multi-Robot Cyber Physical
      System (MRCPS) of a power grid based on inspection robots, a wireless sensor
      network (WSN), and multi-agent theory to achieve a low-cost, efficient, fault
      tolerant, and remote monitoring of power grids. For the sake of an effective
      monitoring system for smart grids, the very research is conducted focusing on
      designing a methodology that will realize the efficient, fault-tolerant, and
      financial balance of a multi-robot team for monitoring transmission lines.
      Multiple testing scenarios are performed, in which various aspects are explored
      so as to determine the optimal parameters balancing team performance and
      financial cost. Furthermore, multi-robot team communication and navigation
      control in smart grid environments are introduced.

PMID- 30231510
TI  - New Molecular Technologies for Minimal Residual Disease Evaluation in B-Cell
      Lymphoid Malignancies.
AB  - The clearance of malignant clonal cells significantly correlates with clinical
      outcomes in many hematologic malignancies. Accurate and high throughput tools for
      minimal residual disease (MRD) detection are needed to overcome some drawbacks of
      standard molecular techniques; such novel tools have allowed for higher
      sensitivity analyses and more precise stratification of patients, based on
      molecular response to therapy. In this review, we depict the recently introduced
      digital PCR and next-generation sequencing technologies, describing their current
      application for MRD monitoring in lymphoproliferative disorders. Moreover, we
      illustrate the feasibility of these new technologies to test less invasive and
      more patient-friendly tissues sources, such as "liquid biopsy".

PMID- 30231511
TI  - The Quality of Tuberculosis Care in Urban Migrant Clinics in China.
AB  - Large and increasing numbers of rural-to-urban migrants provided new challenges
      for tuberculosis control in large cities in China and increased the need for high
      quality tuberculosis care delivered by clinics in urban migrant communities.
      Based on a household survey in migrant communities, we selected and separated
      clinics into those that mainly serve migrants and those that mainly serve local
      residents. Using standardized patients, this study provided an objective
      comparison of the quality of tuberculosis care delivered by both types of clinics
      and examined factors related to quality care. Only 27% (95% confidence interval
      (CI) 14-46) of cases were correctly managed in migrant clinics, which is
      significantly worse than it in local clinics (50%, 95% CI 28-72). Clinicians with
      a base salary were 41 percentage points more likely to demonstrate better case
      management. Furthermore, clinicians with upper secondary or higher education
      level charged 20 RMB lower out of pocket fees than less-educated clinicians. In
      conclusion, the quality of tuberculosis care accessed by migrants was very poor
      and policies to improve the quality should be prioritized in current health
      reforms. Providing a base salary was a possible way to improve quality of care
      and increasing the education attainment of urban community clinicians might
      reduce the heavy barrier of medical expenses for migrants.

PMID- 30231512
TI  - Relationship between Rectal Temperature and Vaginal Temperature in Grazing Bos
      taurus Heifers.
AB  - This study evaluated the relationship between rectal temperature (TREC,  degrees
      C) and vaginal temperature (TVAG,  degrees C) in grazing Bos taurus heifers, to
      develop an understanding of the reliability of these measures as estimates of
      core body temperature. Nineteen Angus heifers (BW = 232.2 +/- 6.91 kg) were
      implanted with intra-rectal and intra-vaginal data loggers. Rectal temperature
      and TVAG were simultaneously recorded at 20 s intervals over 18.5 h. Heifers were
      housed as a singular cohort on grazing pastures for the duration of the study. A
      strong linear relationship (R2 = 0.72, p < 0.0001) between the measurement sites
      was identified. The mean difference between TREC and TVAG was small, in which
      TVAG was on average 0.22 +/- 0.01  degrees C lower than TREC. Individual twenty
      second TREC and TVAG data were used to determine the pooled mean TREC and TVAG
      and then to highlight the within measure variation over time. The coefficient of
      variation was, on average, lower (p < 0.001) for TVAG (0.38%) than TREC (0.44%),
      indicating that TVAG exhibited less variation. Overall, the results from the
      current study suggest that a strong relationship exists between TREC and TVAG,
      and that TVAG may be a more reliable estimate of core body temperature than TREC
      in grazing Bos taurus heifers.

PMID- 30231513
TI  - Molecular and Physiological Study of Candida albicans by Quantitative Proteome
      Analysis.
AB  - Candida albicans is one of the major pathogens that cause the serious infectious
      condition known as candidiasis. C. albicans was investigated by proteome analysis
      to systematically examine its virulence factors and to promote the development of
      novel pharmaceuticals against candidiasis. Here, we review quantitative time
      course proteomics data related to C. albicans adaptation to fetal bovine serum,
      which were obtained using a nano-liquid chromatography/tandem mass spectrometry
      system equipped with a long monolithic silica capillary column. It was revealed
      that C. albicans induced proteins involved in iron acquisition, detoxification of
      oxidative species, energy production, and pleiotropic stress tolerance. Native
      interactions of C. albicans with macrophages were also investigated with the same
      proteome-analysis system. Simultaneous analysis of C. albicans and macrophages
      without isolating individual living cells revealed an attractive strategy for
      studying the survival of C. albicans. Although those data were obtained by
      performing proteome analyses, the molecular physiology of C. albicans is
      discussed and trials related to pharmaceutical applications are also examined.

PMID- 30231508
TI  - Mineralocorticoid Receptor and Aldosterone-Related Biomarkers of End-Organ Damage
      in Cardiometabolic Disease.
AB  - The mineralocorticoid receptor (MR) was first identified as a blood pressure
      regulator, modulating renal sodium handling in response to its principal ligand
      aldosterone. The mineralocorticoid receptor is also expressed in many tissues
      other than the kidney, such as adipose tissue, heart and vasculature. Recent
      studies have shown that MR plays a relevant role in the control of cardiovascular
      and metabolic function, as well as in adipogenesis. Dysregulation of
      aldosterone/MR signaling represents an important cause of disease as high plasma
      levels of aldosterone are associated with hypertension, obesity and increased
      cardiovascular risk. Aldosterone displays powerful vascular effects and acts as a
      potent pro-fibrotic agent in cardiovascular remodeling. Mineralocorticoid
      receptor activation regulates genes involved in vascular and cardiac fibrosis,
      calcification and inflammation. This review focuses on the role of novel
      potential biomarkers related to aldosterone/MR system that could help identify
      cardiovascular and metabolic detrimental conditions, as a result of altered MR
      activation. Specifically, we discuss: (1) how MR signaling regulates the number
      and function of different subpopulations of circulating and intra-tissue immune
      cells; (2) the role of aldosterone/MR system in mediating cardiometabolic
      diseases induced by obesity; and (3) the role of several MR downstream molecules
      as novel potential biomarkers of cardiometabolic diseases, end-organ damage and
      rehabilitation outcome.

PMID- 30231514
TI  - Effects of Clockwise and Counterclockwise Job Shift Work Rotation on Sleep and
      Work-Life Balance on Hospital Nurses.
AB  - Rotational shift work is associated with sleep disturbances, increased risk of
      cardiovascular and psychological disorders, and may negatively impact work-life
      balance. The direction of shift rotation (Clockwise, CW or counterclockwise, CCW)
      and its role in these disorders are poorly understood. The aim of the study was
      to investigate the effect of the shift schedule direction on sleep quantity and
      quality, alertness and work performance, and on work-life balance on hospital
      nurses. One-hundred female nurses, working a continuous rapid shift schedule in
      hospitals in the north of Italy, participated in this cross-sectional study.
      Fifty worked on CW rotation schedule (Morning: 6 a.m.-2 p.m., Afternoon: 2 p.m.
      10 p.m., Night: 10 p.m.-6 a.m., 2 rest days) and fifty on CCW rotation
      (Afternoon, Morning, Morning, Night, 3 rest days). Data were collected by ad hoc
      questionnaire and daily diary. During the shift cycle CW nurses slept longer
      (7.40 +/- 2.24 h) than CCW (6.09 +/- 1.73; p < 0.001). CW nurses reported less
      frequently than CCW awakening during sleep (40% vs. 80%; p < 0.001), attention
      disturbance during work (20% vs. 64%; p < 0.001), and interference with social
      and family life (60% vs. 96% and 20% vs. 70%, respectively; p < 0.001). CCW
      rotating shift schedule seems to be characterized by higher sleep disturbances
      and a worse work-life balance.

PMID- 30231516
TI  - Physico-Chemical and Antifungal Properties of a Trypsin Inhibitor from the Roots
      of Pseudostellaria heterophylla.
AB  - Plant peptidase inhibitors play essential roles in the defense systems of plants.
      A trypsin inhibitor (PHTI) with a molecular mass of 20.5 kDa was isolated from
      the fresh roots of the medicinal herb, Pseudostellaria heterophylla. The
      purification process involved ammonium sulfate precipitation, gel filtration
      chromatography on Sephadex G50, and ion-exchange chromatography on DEAE 650M. The
      PHTI contained 3.7% alpha-helix, 42.1% beta-sheets, 21.2% beta-turns, and 33%
      disordered structures, which showed similarity with several Kunitz-type trypsin
      inhibitors. Inhibition kinetic studies indicated that PHTI was a competitive
      inhibitor, with a Ki value of 3.01 * 10-9 M, indicating a high affinity to
      trypsin. The PHTI exhibited considerable stability over a broad range of pH (2
      10) and temperatures (20-70  degrees C); however, metal ions, including Fe3+,
      Ba2+, Mn2+, and Al3+, could inactivate PHTI to different degrees. Results of
      fluorescence spectroscopy and circular dichroism showed that Fe3+ could bind to
      TI with an association constant of 2.75 * 105 M-1 to form a 1:1 complex, inducing
      conformation changes and inactivation of PHTI. In addition, PHTI could inhibit
      the growth of the phytopathogens, Colletotrichum gloeosporioides and Fusarium
      oxysporum, through disruption of the cell membrane integrity. The present study
      extended research on Pseudostellaria heterophylla proteins and makes PHTI an
      exploitable candidate as an antifungal protein for further investigation.

PMID- 30231518
TI  - SA4503, A Potent Sigma-1 Receptor Ligand, Ameliorates Synaptic Abnormalities and
      Cognitive Dysfunction in a Mouse Model of ATR-X Syndrome.
AB  - alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by
      mutations in ATRX. An ATR-X model mouse lacking Atrx exon 2 displays phenotypes
      that resemble symptoms in the human intellectual disability: cognitive defects
      and abnormal dendritic spine formation. We herein target activation of sigma-1
      receptor (Sig-1R) that can induce potent neuroprotective and neuroregenerative
      effects by promoting the activity of neurotrophic factors, such as brain-derived
      neurotrophic factor (BDNF). We demonstrated that treatment with SA4503, a potent
      activator of Sig-1R, reverses axonal development and dendritic spine
      abnormalities in cultured cortical neurons from ATR-X model mice. Moreover, the
      SA4503 treatment rescued cognitive deficits exhibited by the ATR-X model mice. We
      further found that significant decreases in the BDNF-protein level in the medial
      prefrontal cortex of ATR-X model mice were recovered with treatment of SA4503.
      These results indicate that the rescue of dendritic spine abnormalities through
      the activation of Sig-1R has a potential for post-diagnostic therapy in ATR-X
      syndrome.

PMID- 30231515
TI  - Interferon-Mediated Response to Human Metapneumovirus Infection.
AB  - Human metapneumovirus (HMPV) is one of the leading causes of respiratory diseases
      in infants and children worldwide. Although this pathogen infects mainly young
      children, elderly and immunocompromised people can be also seriously affected. To
      date, there is no commercial vaccine available against it. Upon HMPV infection,
      the host innate arm of defense produces interferons (IFNs), which are critical
      for limiting HMPV replication. In this review, we offer an updated landscape of
      the HMPV mediated-IFN response in different models as well as some of the defense
      tactics employed by the virus to circumvent IFN response.

PMID- 30231519
TI  - Physiological Changes as a Measure of Crustacean Welfare under Different
      Standardized Stunning Techniques: Cooling and Electroshock.
AB  - Stunning of edible crustaceans to reduce sensory perception prior and during
      slaughter is an important topic in animal welfare. The purpose of this project
      was to determine how neural circuits were affected during stunning by examining
      the physiological function of neural circuits. The central nervous system circuit
      to a cardiac or skeletal muscle response was examined. Three commercially
      important crustacean species were utilized for stunning by immersion in an ice
      slurry below 4  degrees C and by electrocution; both practices are used in the
      seafood industry. The blue crab (Callinectes sapidus), the red swamp crayfish
      (Procambarus clarkii), and the whiteleg shrimp (Litopenaeus vannamei) responded
      differently to stunning by cold and electric shock. Immersion in ice slurry
      induced sedation within seconds in crayfish and shrimp but not crabs and cardiac
      function was reduced fastest in shrimp. However, crabs could retain a functional
      neural circuit over the same time when shrimp and crayfish were nonresponsive. An
      electroshock of 10 s paralyzed all three species and subsequently decreased heart
      rate within 1 min and then heart rate increased but resulted in irregularity over
      time. Further research is needed to study a state of responsiveness by these
      methods.

PMID- 30231517
TI  - Graphene-Based Light Sensing: Fabrication, Characterisation, Physical Properties
      and Performance.
AB  - Graphene and graphene-based materials exhibit exceptional optical and electrical
      properties with great promise for novel applications in light detection. However,
      several challenges prevent the full exploitation of these properties in
      commercial devices. Such challenges include the limited linear dynamic range
      (LDR) of graphene-based photodetectors, the lack of efficient generation and
      extraction of photoexcited charges, the smearing of photoactive junctions due to
      hot-carriers effects, large-scale fabrication and ultimately the environmental
      stability of the constituent materials. In order to overcome the aforementioned
      limits, different approaches to tune the properties of graphene have been
      explored. A new class of graphene-based devices has emerged where chemical
      functionalisation, hybridisation with light-sensitising materials and the
      formation of heterostructures with other 2D materials have led to improved
      performance, stability or versatility. For example, intercalation of graphene
      with FeCl 3 is highly stable in ambient conditions and can be used to define
      photo-active junctions characterized by an unprecedented LDR while graphene oxide
      (GO) is a very scalable and versatile material which supports the photodetection
      from UV to THz frequencies. Nanoparticles and quantum dots have been used to
      enhance the absorption of pristine graphene and to enable high gain thanks to the
      photogating effect. In the same way, hybrid detectors made from stacked sequences
      of graphene and layered transition-metal dichalcogenides enabled a class of
      devices with high gain and responsivity. In this work, we will review the
      performance and advances in functionalised graphene and hybrid photodetectors,
      with particular focus on the physical mechanisms governing the photoresponse, the
      performance and possible future paths of investigation.

PMID- 30231520
TI  - d-Amino Acid Pseudopeptides as Potential Amyloid-Beta Aggregation Inhibitors.
AB  - A causative factor for neurotoxicity associated with Alzheimer's disease is the
      aggregation of the amyloid-beta (Abeta) peptide into soluble oligomers. Two all d
      amino acid pseudo-peptides, SGB1 and SGD1, were designed to stop the aggregation.
      Molecular dynamics (MD) simulations have been carried out to study the
      interaction of the pseudo-peptides with both Abeta13-23 (the core recognition
      site of Abeta) and full-length Abeta1-42. Umbrella sampling MD calculations have
      been used to estimate the free energy of binding, ?G, of these peptides to
      Abeta13-23. The highest ?Gbinding is found for SGB1. Each of the pseudo-peptides
      was also docked to Abeta1-42 and subjected up to seven microseconds of all atom
      molecular dynamics simulations. The resulting structures lend insight into how
      the dynamics of Abeta1-42 are altered by complexation with the pseudo-peptides
      and confirmed that SGB1 may be a better candidate for developing into a drug to
      prevent Alzheimer's disease.

PMID- 30231522
TI  - A Reduced GO-Graphene Hybrid Gas Sensor for Ultra-Low Concentration Ammonia
      Detection.
AB  - A hybrid structure gas sensor of reduced graphene oxide (RGO) decorated graphene
      (RGO-Gr) is designed for ultra-low concentration ammonia detection. The
      resistance value of the RGO-Gr hybrid is the indicator of the ammonia
      concentration and controlled by effective charge transport from RGO to graphene
      after ammonia molecule adsorption. In this hybrid material, RGO is the adsorbing
      layer to catch ammonia molecules and graphene is the conductive layer to
      effectively enhance charge/electron transport. Compared to a RGO gas sensor, the
      signal-to-noise ratio (SNR) of the RGO-Gr is increased from 22 to 1008.
      Meanwhile, the response of the RGO-Gr gas sensor is better than that of either a
      pristine graphene or RGO gas sensor. It is found that the RGO reduction time is
      related to the content of functional groups that directly reflect on the gas
      sensing properties of the sensor. The RGO-Gr gas sensor with 10 min reduction
      time has the best gas sensing properties in this type of sensor. The highest
      sensitivity is 2.88% towards 0.5 ppm, and the ammonia gas detection limit is
      calculated to be 36 ppb.

PMID- 30231523
TI  - Health Risks Associated with Occupational Exposure to Ambient Air Pollution in
      Commercial Drivers: A Systematic Review.
AB  - Ambient air pollution is a major global health problem and commercial drivers are
      particularly exposed to it. As no systematic assessment of the health risks
      associated with occupational exposure to ambient air pollution in this population
      had yet been carried out, we conducted a systematic review using a protocol
      driven strategy. Papers published from inception to April 20, 2018 in MEDLINE,
      EMBASE, CINAHL, African journals online, the Cochrane library, ISRCTN WHO ICTRP,
      and the Web of Science and Scopus databases were screened for inclusion by two
      independent reviewers. Original articles with at least an available abstract in
      English or French were included. The initial search retrieved 1454 published
      articles of which 20 articles were included. Three studies reported a significant
      difference in white blood cells (106/L) among commercial motorcyclists compared
      to rural inhabitants (5.041 +/- 1.209 vs. 5.900 +/- 1.213, p = 0.001), an
      increased risk of lung cancer (RR = 1.6, 95%CI 1.5-1.8) in bus drivers and an
      increased standardized mortality ratio (SMR) in bus drivers from Hodgkin's
      lymphoma (SMR 2.17, 95%CI 1.19-3.87) compared to white-collar workers. Other
      studies also found that drivers had more oxidative DNA damage and chromosome
      breaks. Four papers failed to demonstrate that the drivers were more exposed to
      air pollution than the controls. Three other studies also reported no significant
      difference in lung function parameters and respiratory symptoms. The genetic
      polymorphisms of detoxifying enzymes were also not homogeneously distributed
      compared to the controls. There is some evidence that occupational exposure to
      ambient air pollution among commercial drivers is associated with adverse health
      outcomes, but the existing literature is limited, with few studies on small
      sample size, methodological weaknesses, and contradictory findings-thus, further
      research is recommended.

PMID- 30231524
TI  - Selective Laser Melting Strategy for Fabrication of Thin Struts Usable in Lattice
      Structures.
AB  - This paper deals with the selective laser melting (SLM) processing strategy for
      strut-lattice structure production which uses only contour lines and allows the
      porosity and roughness level to be managed based on combination of the input and
      linear energy parameters. To evaluate the influence of a laser scanning strategy
      on material properties and surface roughness a set of experiments was performed.
      The single welds test was used to find the appropriate processing parameters to
      achieve continuous welds with known width. Strut samples were used to find a
      suitable value of weld overlapping and to clarify the influence of input and
      linear laser energy on the strut porosity and surface roughness. The samples of
      inclined hollow struts were used to compare the wall thickness with single welds
      width; the results showed about 25% wider welds in the case of a hollow strut.
      Using the proposed SLM strategy it is possible to reach a significantly lower
      porosity and surface roughness of the struts. The best results for struts with an
      inclination of 35.26 degrees  were achieved with 25% track overlapping, input
      energy in the range from 9 J to 10.5 J and linear energy Elin from 0.25 to 0.4
      J/mm; in particular, the relative density of 99.83% and the surface roughness on
      the side of the strut of Ra 14.6 MUm in an as-built state was achieved.

PMID- 30231525
TI  - Astaxanthin Inhibits Mitochondrial Dysfunction and Interleukin-8 Expression in
      Helicobacter pylori-Infected Gastric Epithelial Cells.
AB  - Helicobacter pylori (H. pylori) infection leads to gastric inflammation, peptic
      ulcer and gastric carcinoma. H. pylori activates NADPH oxidase and increases
      reactive oxygen species (ROS), which induce NF-kappaB activation and IL-8
      expression in gastric epithelial cells. Dysfunctional mitochondria trigger
      inflammatory cytokine production. Peroxisome proliferator-activated receptors
      gamma (PPAR-gamma) regulate inflammatory response. Astaxanthin is a powerful
      antioxidant that protects cells against oxidative stress. The present study was
      aimed at determining whether astaxanthin inhibits H. pylori-induced mitochondrial
      dysfunction, NF-kappaB activation, and IL-8 expression via PPAR-gamma activation
      in gastric epithelial cells. Gastric epithelial AGS cells were treated with
      astaxanthin, NADPH oxidase inhibitor apocynin and PPAR-gamma antagonist GW9662,
      and infected with H. pylori. As a result, H. pylori caused an increase in
      intracellular and mitochondrial ROS, NF-kappaB activation and IL-8 expression,
      but decreased mitochondrial membrane potential and ATP level. Astaxanthin
      inhibited H. pylori-induced alterations (increased ROS, mitochondrial
      dysfunction, NF-kappaB activation, and IL-8 expression). Astaxanthin activated
      PPAR-gamma and its target gene catalase in H. pylori-infected cells. Apocynin
      reduced ROS and inhibited IL-8 expression while astaxanthin did not affect NADPH
      oxidase activity. Inhibitory effects of astaxanthin on ROS levels and IL-8
      expression were suppressed by addition of GW9662. In conclusion, astaxanthin
      inhibits H. pylori-induced mitochondrial dysfunction and ROS-mediated IL-8
      expression by activating PPAR-gamma and catalase in gastric epithelial cells.
      Astaxanthin may be beneficial for preventing oxidative stress-mediated gastric
      inflammation-associated H. pylori infection.

PMID- 30231521
TI  - Hydrogen Peroxide: Its Role in Plant Biology and Crosstalk with Signalling
      Networks.
AB  - Hydrogen peroxide (H2O2) is steadily gaining more attention in the field of
      molecular biology research. It is a major REDOX (reduction-oxidation reaction)
      metabolite and at high concentrations induces oxidative damage to biomolecules,
      which can culminate in cell death. However, at concentrations in the low
      nanomolar range, H2O2 acts as a signalling molecule and in many aspects,
      resembles phytohormones. Though its signalling network in plants is much less
      well characterized than are those of its counterparts in yeast or mammals,
      accumulating evidence indicates that the role of H2O2-mediated signalling in
      plant cells is possibly even more indispensable. In this review, we summarize
      hydrogen peroxide metabolism in plants, the sources and sinks of this compound
      and its transport via peroxiporins. We outline H2O2 perception, its direct and
      indirect effects and known targets in the transcriptional machinery. We focus on
      the role of H2O2 in plant growth and development and discuss the crosstalk
      between it and phytohormones. In addition to a literature review, we performed a
      meta-analysis of available transcriptomics data which provided further evidence
      for crosstalk between H2O2 and light, nutrient signalling, temperature stress,
      drought stress and hormonal pathways.

PMID- 30231526
TI  - Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7
      Ethylcamptothecin.
AB  - A previous study showed that intravenous immunoglobulin (IVIG) could preserve
      higher levels of biologically active lactone moieties of topotecan, 7-ethyl-10
      hydroxycamptothecin (SN-38) and 10-hydroxycamptothecin at physiological pH 7.40.
      As one of camptothecin analogues (CPTs), the interaction of 7-ethylcamptothecin
      and IVIG was studied in vitro in this study. It was shown that the main binding
      mode of IVIG to 7-ethylcamptothecin was hydrophobic interaction and hydrogen
      bonding, which is a non-specific and spontaneous interaction. The hydrophobic
      antigen-binding cavity of IgG would enwrap the drug into a host-guest inclusion
      complex and prevent hydrolysis of the encapsulated drug, while the drug is
      adjacent to the chromophores of IgG and may exchange energy with chromophores and
      quench the fluorescence of the protein. Also, the typical beta-sheet structure of
      IVIG unfolded partially after binding to 7-ethylcamptothecin. Additionally, the
      binding properties of IVIG and six CPTs with different substituents at A-ring
      and/or B-ring including camptothecin, topotecan, irinotecan, 10
      hydroxycamptothecin, 7-ethylcamptothecin and SN-38 were collected together and
      compared each other. Synergizing with anti-cancer drugs, IVIG could be used as a
      transporter protein for 7-ethylcamptothecin and other CPTs, allowing clinicians
      to devise new treatment protocols for patients.

PMID- 30231527
TI  - The Role of Objectively Measured, Altered Physical Activity Patterns for Body
      Mass Index Change during Inpatient Treatment in Female Patients with Anorexia
      Nervosa.
AB  - Increased physical activity (PA) affects outcomes in patients with anorexia
      nervosa (AN). To objectively assess PA patterns of hospitalized AN patients in
      comparison with healthy, outpatient controls (HC), and to analyze the effect of
      PA on Body Mass Index (BMI) change in patients with AN, we measured PA in 50
      female patients with AN (median age = 25 years, range = 18-52 years; mean BMI =
      14.4 +/- 2.0 kg/m2) at the initiation of inpatient treatment and in 30 female
      healthy controls (median age = 26 years, range = 19-53 years; mean BMI = 21.3 +/-
      1.7 kg/m2) using the SenseWearTM armband. Duration of inpatient stay and weight
      at discharge were abstracted from medical records. Compared with controls, AN
      patients spent more time in very light-intensity physical activity (VLPA) (median
      VLPA = 647 vs. 566 min/day, p = 0.004) and light-intensity physical activity
      (LPA) (median LPA = 126 vs. 84 min/day, p < 0.001) and less time in moderate
      intensity physical activity (MPA) (median MPA = 82 vs. 114 min/day, p = 0.022)
      and vigorous physical activity (VPA) (median VPA = 0 vs. 16 min/day, p < 0.001).
      PA and BMI increase were not associated in a linear model, and BMI increase was
      mostly explained by lower admission BMI and longer inpatient stay. In a non
      linear model, an influence of PA on BMI increase seemed probable (jack knife
      validation, r2 = 0.203; p < 0.001). No direct association was observed between
      physical inactivity and BMI increase in AN. An altered PA pattern exists in AN
      patients compared to controls, yet the origin and consequences thereof deserve
      further investigation.

PMID- 30231529
TI  - 3DoF+ 360 Video Location-Based Asymmetric Down-Sampling for View Synthesis to
      Immersive VR Video Streaming.
AB  - Recently, with the increasing demand for virtual reality (VR), experiencing
      immersive contents with VR has become easier. However, a tremendous amount of
      calculation and bandwidth is required when processing 360 videos. Moreover,
      additional information such as the depth of the video is required to enjoy
      stereoscopic 360 contents. Therefore, this paper proposes an efficient method of
      streaming high-quality 360 videos. To reduce the bandwidth when streaming and
      synthesizing the 3DoF+ 360 videos, which supports limited movements of the user,
      a proper down-sampling ratio and quantization parameter are offered from the
      analysis of the graph between bitrate and peak signal-to-noise ratio. High
      efficiency video coding (HEVC) is used to encode and decode the 360 videos, and
      the view synthesizer produces the video of intermediate view, providing the user
      with an immersive experience.

PMID- 30231528
TI  - Mimiviridae: An Expanding Family of Highly Diverse Large dsDNA Viruses Infecting
      a Wide Phylogenetic Range of Aquatic Eukaryotes.
AB  - Since 1998, when Jim van Etten's team initiated its characterization, Paramecium
      bursaria Chlorella virus 1 (PBCV-1) had been the largest known DNA virus, both in
      terms of particle size and genome complexity. In 2003, the Acanthamoeba-infecting
      Mimivirus unexpectedly superseded PBCV-1, opening the era of giant viruses, i.e.,
      with virions large enough to be visible by light microscopy and genomes encoding
      more proteins than many bacteria. During the following 15 years, the isolation of
      many Mimivirus relatives has made Mimiviridae one of the largest and most diverse
      families of eukaryotic viruses, most of which have been isolated from aquatic
      environments. Metagenomic studies of various ecosystems (including soils) suggest
      that many more remain to be isolated. As Mimiviridae members are found to infect
      an increasing range of phytoplankton species, their taxonomic position compared
      to the traditional Phycodnaviridae (i.e., etymologically "algal viruses") became
      a source of confusion in the literature. Following a quick historical review of
      the key discoveries that established the Mimiviridae family, we describe its
      current taxonomic structure and propose a set of operational criteria to help in
      the classification of future isolates.

PMID- 30231530
TI  - A Cross Sectional Examination of the Relation Between Depression and Frequency of
      Leisure Time Physical Exercise among the Elderly in Jinan, China.
AB  - Depression has become a major global public health problem. Many studies have
      shown the positive effects of physical exercise on depression. However, few
      studies have examined the relationship between frequency of leisure time physical
      exercise and depression without considering the time and intensity of exercise
      among middle-aged and elderly people of urban communities in northern China. We
      conducted a cross-sectional survey that included 1604 participants among urban
      residents aged 50 years or older in China to evaluate how the frequency of
      physical exercise was related to depression. Our study showed that the prevalence
      of depression in the urban community of Jinan is 16.52%. For physical exercise,
      the odds ratios (ORs) and 95% confidence intervals (CIs) for 1~2 times per week,
      3~4 times per week and >=5 times per week were 1.137 (0.661, 1.953), 0.516
      (0.304, 0.875) and 0.548 (0.392, 0.768) respectively, with adjustment for age,
      gender, marital status, BMI, hypertension, previously diagnosed type 2 diabetes,
      triglyceride, total cholesterol, soy food intake, milk food intake, vegetable and
      fruit intake and meat intake. We concluded that physically exercising three times
      a week is associated with a low prevalence of depression.

PMID- 30231531
TI  - Adherence to the Mediterranean Diet among School Children and Adolescents Living
      in Northern Italy and Unhealthy Food Behaviors Associated to Overweight.
AB  - The purposes of this study were to evaluate the differences in Mediterranean diet
      and its components among primary and secondary school children and adolescents
      living in northern Italy, and the associations with the weight status. Adherence
      was assessed by the KIDMED (Mediterranean Diet Quality Index) questionnaire on
      669 subjects (6-16 years) attending five schools of Novara. The adherence was
      poor in 16.7%, average in 63.7%, and high in 19.6% of the students. Poor
      adherence was more frequent in primary than in secondary schools (20.7% vs.
      13.7%, p < 0.04). Some unhealthy behaviors were more prevalent in younger
      children. Children of other ethnic origins had a mixed behavior, choosing both
      traditional healthy and unhealthy foods. Besides male gender and primary school,
      in Italian children, the risk of overweight was directly associated with eating
      at fast-food restaurants (OR: 1.890, CI 95% 1.002-3.563), and inversely with
      consumption of vegetables more than once a day (OR: 0.588, CI 95% 0.349-0.991),
      and olive oil at home (OR: 0.382, CI 95% 0.176-0.826). In children of other
      ethnic origins, this risk was associated with skipping breakfast (OR: 16.046, CI
      95% 1.933-133.266), or consuming commercial baked good or pastries for breakfast
      (OR: 10.255, CI 95% 1.052-99.927). The overall KIDMED score correlated with
      height (beta: 0.108; p < 0.005). Poor food quality is replacing the Mediterranean
      dietary pattern in children and adolescents, in particular among younger
      children. Because the risk of overweight was associated with different components
      of the Mediterranean diet depending on ethnic origins, tailored nutritional
      programs remain a need.

PMID- 30231534
TI  - Smartphone-Based Traveled Distance Estimation Using Individual Walking Patterns
      for Indoor Localization.
AB  - We introduce a novel method for indoor localization with the user's own
      smartphone by learning personalized walking patterns outdoors. Most smartphone
      and pedestrian dead reckoning (PDR)-based indoor localization studies have used
      an operation between step count and stride length to estimate the distance
      traveled via generalized formulas based on the manually designed features of the
      measured sensory signal. In contrast, we have applied a different approach to
      learn the velocity of the pedestrian by using a segmented signal frame with our
      proposed hybrid multiscale convolutional and recurrent neural network model, and
      we estimate the distance traveled by computing the velocity and the moved time.
      We measured the inertial sensor and global position service (GPS) position at a
      synchronized time while walking outdoors with a reliable GPS fix, and we assigned
      the velocity as a label obtained from the displacement between the current
      position and a prior position to the corresponding signal frame. Our proposed
      real-time and automatic dataset construction method dramatically reduces the cost
      and significantly increases the efficiency of constructing a dataset. Moreover,
      our proposed deep learning model can be naturally applied to all kinds of time
      series sensory signal processing. The performance was evaluated on an Android
      application (app) that exported the trained model and parameters. Our proposed
      method achieved a distance error of <2.4% and >1.5% on indoor experiments.

PMID- 30231535
TI  - The Measure of the Family Caregivers' Experience.
AB  - Objective: Design and validate a measure of the experience of family caregivers
      with the integrated care that receive the persons they care for. Methods: The new
      instrument for measuring the experience of caregivers is based on the Instrument
      to Evaluate the EXperience of PAtients with Chronic Diseases (acronym in Spanish:
      IEXPAC) scale instrument. With the qualitative technique of the discussion group,
      nine professionals and eight caregivers assessed the face validity of the
      instrument and they advised on issues to explore and the measuring scale to use.
      The instrument's items were analyzed individually, as well as its consistency,
      reliability, and construct and empirical validity. Results: 235 caregivers
      responded, of which 186 (79%) were women. The average age of the persons under
      their care was 83.9 years (SD 9.7). The scale's score when eliminating its items
      one by one ranged between 38.6 and 41.1. The factorial saturations of the items
      ranged between 0.53 and 0.82. Cronbach's alpha (12 elements) was 0.88 and the
      Kuder-Richardson coefficient was 0.91. The factorial solution explained 64.3% of
      the total variance and allowed isolating two factors (with 11 items with
      saturations greater than 0.65): care for the patient, and care for the caregiver.
      The internal consistency of both factors was greater than 0.80. The scale's score
      was 41.1 (SD 9.7). Conclusions: The Caregivers Experience Instrument combines
      acceptability, ease of comprehension, and perceived usefulness for the
      caregivers. It has adequate internal consistency, reliability, and construct and
      empirical validity.

PMID- 30231536
TI  - A Type of Annulus-Based Energy Balanced Data Collection Method in Wireless
      Rechargeable Sensor Networks.
AB  - With the increasing number of ubiquitous terminals and the continuous expansion
      of network scale, the problem of unbalanced energy consumption in sensor networks
      has become increasingly prominent in recent years. However, a node scheduling
      strategy or an energy consumption optimization algorithm may be not enough to
      meet the requirements of large-scale application. To address this problem a type
      of Annulus-based Energy Balanced Data Collection (AEBDC) method is proposed in
      this paper. The circular network is divided into several annular sectors of
      different sizes. Nodes in the same annulus-sector form a cluster. Based on this
      model, a multi-hop data forwarding strategy with the help of the candidate
      cluster headers is proposed to balance energy consumption during transmission and
      to avoid buffer overflow. Meanwhile, in each annulus, there is a Wireless
      Charging Vehicle (WCV) that is responsible for periodically recharging the
      cluster headers as well as the candidate cluster headers. By minimizing the
      recharging cost, the energy efficiency is enhanced. Simulation results show that
      AEBDC can not only alleviate the "energy hole problem" in sensor networks, but
      also effectively prolong the network lifetime.

PMID- 30231532
TI  - The Effect of Lutein on Eye and Extra-Eye Health.
AB  - Lutein is a carotenoid with reported anti-inflammatory properties. A large body
      of evidence shows that lutein has several beneficial effects, especially on eye
      health. In particular, lutein is known to improve or even prevent age-related
      macular disease which is the leading cause of blindness and vision impairment.
      Furthermore, many studies have reported that lutein may also have positive
      effects in different clinical conditions, thus ameliorating cognitive function,
      decreasing the risk of cancer, and improving measures of cardiovascular health.
      At present, the available data have been obtained from both observational studies
      investigating lutein intake with food, and a few intervention trials assessing
      the efficacy of lutein supplementation. In general, sustained lutein consumption,
      either through diet or supplementation, may contribute to reducing the burden of
      several chronic diseases. However, there are also conflicting data concerning
      lutein efficacy in inducing favorable effects on human health and there are no
      univocal data concerning the most appropriate dosage for daily lutein
      supplementation. Therefore, based on the most recent findings, this review will
      focus on lutein properties, dietary sources, usual intake, efficacy in human
      health, and toxicity.

PMID- 30231533
TI  - Mitochondrial Targeting in Neurodegeneration: A Heme Perspective.
AB  - Mitochondrial dysfunction has achieved an increasing interest in the field of
      neurodegeneration as a pathological hallmark for different disorders. The impact
      of mitochondria is related to a variety of mechanisms and several of them can co
      exist in the same disease. The central role of mitochondria in neurodegenerative
      disorders has stimulated studies intended to implement therapeutic protocols
      based on the targeting of the distinct mitochondrial processes. The review
      summarizes the most relevant mechanisms by which mitochondria contribute to
      neurodegeneration, encompassing therapeutic approaches. Moreover, a new
      perspective is proposed based on the heme impact on neurodegeneration. The heme
      metabolism plays a central role in mitochondrial functions, and several evidences
      indicate that alterations of the heme metabolism are associated with
      neurodegenerative disorders. By reporting the body of knowledge on this topic,
      the review intends to stimulate future studies on the role of heme metabolism in
      neurodegeneration, envisioning innovative strategies in the struggle against
      neurodegenerative diseases.

PMID- 30231537
TI  - Deletion of Bmal1 Prevents Diet-Induced Ectopic Fat Accumulation by Controlling
      Oxidative Capacity in the Skeletal Muscle.
AB  - Brain and muscle arnt-like protein 1 (BMAL1), is a transcription factor known to
      regulate circadian rhythm. BMAL1 was originally characterized by its high
      expression in the skeletal muscle. Since the skeletal muscle is the dominant
      organ system in energy metabolism, the possible functions of BMAL1 in the
      skeletal muscle include the control of metabolism. Here, we established that its
      involvement in the regulation of oxidative capacity in the skeletal muscle.
      Muscle-specific Bmal1 KO mice (MKO mice) displayed several physiological
      hallmarks for the increase of oxidative capacity. This included increased energy
      expenditure and oxygen consumption, high running endurance and resistance to
      obesity with improved metabolic profiles. Also, the phosphorylation status of AMP
      activated protein kinase and its downstream signaling substrate acetyl-CoA
      carboxylase in the MKO mice were substantially higher than those in the
      Bmal1flox/flox mice. In addition, biochemical and histological studies confirmed
      the substantial activation of oxidative fibers in the skeletal muscle of the MKO
      mice. The mechanism includes the regulation of Cacna1s expression, followed by
      the activation of calcium-nuclear factor of activated T cells (NFAT) axis. We
      thus conclude that BMAL1 is a critical regulator of the muscular fatty acid level
      under nutrition overloading and that the mechanism involves the control of
      oxidative capacity.

PMID- 30231538
TI  - High-Throughput Direct Mass Spectrometry-Based Metabolomics to Characterize
      Metabolite Fingerprints Associated with Alzheimer's Disease Pathogenesis.
AB  - Direct mass spectrometry-based metabolomics has been widely employed in recent
      years to characterize the metabolic alterations underlying Alzheimer's disease
      development and progression. This high-throughput approach presents great
      potential for fast and simultaneous fingerprinting of a vast number of
      metabolites, which can be applied to multiple biological matrices including
      serum/plasma, urine, cerebrospinal fluid and tissues. In this review article, we
      present the main advantages and drawbacks of metabolomics based on direct mass
      spectrometry compared with conventional analytical techniques, and provide a
      comprehensive revision of the literature on the use of these tools in the
      investigation of Alzheimer's disease.

PMID- 30231539
TI  - Natural and Modified Montmorillonite Clays as Catalysts for Synthesis of
      Biolubricants.
AB  - In this study, natural and modified clays were evaluated as catalysts in an
      esterification reaction to obtain bio-based lubricants. The biolubricants are
      environmentally preferred to petroleum-based lubricants because they are
      biodegradable and non-toxic. Other advantages include very low volatility due to
      the high molecular weight and excellent viscosity properties with temperature
      variations. Modifications in natural clay were performed intending to obtain
      materials with different textural properties that could improve the reaction
      under study. The modified clays were obtained in two ways: by pillarization using
      Al13 Keggin polyoxocations or by acid treatments with H2SO4, HCl and HNO3. All
      samples were evaluated for the esterification reaction of fatty acids from castor
      oil (FACO) using 2-ethyl-hexanol. During the reaction step, a zeolite-based
      adsorbent was used for water removal to increase the reaction equilibrium
      conversion. Gas chromatography and nuclear magnetic resonance were performed to
      ensure the formation of the products. The highest conversion of fatty acids to
      esters was obtained using pillared clays. Adding adsorbent in the reaction medium
      (10 g of 3A zeolite to 100 g of FACO), the conversion improved from 74-88 wt %
      after 6 h at 50  degrees C.

PMID- 30231540
TI  - On the Interactions and Synergism between Phases of Carbon-Phosphorus-Titanium
      Composites Synthetized from Cellulose for the Removal of the Orange-G Dye.
AB  - Carbon-phosphorus-titanium composites (CPT) were synthesized by Ti-impregnation
      and carbonization of cellulose. Microcrystalline cellulose used as carbon
      precursor was initially dissolved by phosphoric acid (H3PO4) to favor the Ti
      dispersion and the simultaneous functionalization of the cellulose chains with
      phosphorus-containing groups, namely phosphates and polyphosphates. These groups
      interacted with the Ti-precursor during impregnation and determined the interface
      transformations during carbonization as a function of the Ti-content and
      carbonization temperature. Amorphous composites with high surface area and
      mesoporosity were obtained at low Ti-content (Ti:cellulose ratio = 1) and
      carbonization temperature (500  degrees C), while in composites with Ti:cellulose
      ratio = 12 and 800  degrees C, Ti-particles reacted with the cellulose groups
      leading to different Ti-crystalline polyphosphates and a marked loss of the
      porosity. The efficiency of composites in the removal of the Orange G dye in
      solution by adsorption and photocatalysis was discussed based on their
      physicochemical properties. These materials were more active than the benchmark
      TiO2 material (Degussa P25), showing a clear synergism between phases.

PMID- 30231541
TI  - Transcriptional Homeostasis of Oxidative Stress-Related Pathways in Altered
      Gravity.
AB  - Whereby several types of cultured cells are sensitive to gravity, the immune
      system belongs to the most affected systems during spaceflight. Since reactive
      oxygen species/reactive nitrogen species (ROS/RNS) are serving as signals of
      cellular homeostasis, particularly in the cells of the immune system, we
      investigated the immediate effect of altered gravity on the transcription of 86
      genes involved in reactive oxygen species metabolism, antioxidative systems, and
      cellular response to oxidative stress, using parabolic flight and suborbital
      ballistic rocket experiments and microarray analysis. In human myelomonocytic
      U937 cells, we detected a rapid response of 19.8% of all of the investigated
      oxidative stress-related transcripts to 1.8 g of hypergravity and 1.1% to
      microgravity as early as after 20 s. Nearly all (97.2%) of the initially altered
      transcripts adapted after 75 s of hypergravity (max. 13.5 g), and 100% adapted
      after 5 min of microgravity. After the almost complete adaptation of initially
      altered transcripts, a significant second pool of differentially expressed
      transcripts appeared. In contrast, we detected nearly no response of oxidative
      stress-related transcripts in human Jurkat T cells to altered gravity. In
      conclusion, we assume a very well-regulated homeostasis and transcriptional
      stability of oxidative stress-related pathways in altered gravity in cells of the
      human immune system.

PMID- 30231542
TI  - The Effect of White Rice and White Bread as Staple Foods on Gut Microbiota and
      Host Metabolism.
AB  - The purpose of this study was to examine the influence of two kinds of major
      Japanese staple foods, white rice and white bread, on gut microbiota against the
      background in which participants eat common side dishes. Seven healthy subjects
      completed the dietary intervention with two 1-week test periods with a 1-week
      wash-out period in cross-over design (UMIN registration UMIN000023142). White
      bread or white rice and 21 frozen prepared side dishes were consumed during the
      test periods. At baseline and at the end of each period, fasting blood samples,
      breath samples, and fecal samples were collected. For fecal samples, 16S rRNA
      gene sequencing was used to analyze the gut microbiota. After the bread period,
      the abundance of fecal Bifidobacterium genus (19.2 +/- 14.5 vs. 6.2 +/- 6.6 (%),
      p = 0.03), fasting glucagon-like peptide 1 (GLP-1) (13.6 +/- 2.0 vs. 10.5 +/- 2.9
      (pg/mL), p = 0.03), and breath hydrogen (23.4 +/- 9.9 vs. 8.2 +/- 5.5 (ppm), p =
      0.02) were significantly higher than those of after the rice period. Plasma SCFAs
      also tended to be higher after the bread period. White bread contains more
      dietary fiber than refined short grain rice. These findings suggest that
      indigestible carbohydrate intake from short grain rice as a staple food may be
      smaller than that of white bread.

PMID- 30231544
TI  - Design, Synthesis and Evaluation of N-pyrazinylbenzamides as Potential
      Antimycobacterial Agents.
AB  - Three series of N-(pyrazin-2-yl)benzamides were designed as retro-amide analogues
      of previously published N-phenylpyrazine-2-carboxamides with in vitro
      antimycobacterial activity. The synthesized retro-amides were evaluated for in
      vitro growth inhibiting activity against Mycobacterium tuberculosis H37Rv (Mtb),
      three non-tuberculous mycobacterial strains (M. avium, M. kansasii, M. smegmatis)
      and selected bacterial and fungal strains of clinical importance. Regarding
      activity against Mtb, most N-pyrazinylbenzamides (retro-amides) possessed lower
      or no activity compared to the corresponding N-phenylpyrazine-2-carboxamides with
      the same substitution pattern. However, the active retro-amides tended to have
      lower HepG2 cytotoxicity and better selectivity. Derivatives with 5-chloro
      substitution on the pyrazine ring were generally more active compared to their 6
      cloro positional isomers or non-chlorinated analogues. The best antimycobacterial
      activity against Mtb was found in N-(5-chloropyrazin-2-yl)benzamides with short
      alkyl (2h: R2 = Me; 2i: R2 = Et) in position 4 of the benzene ring (MIC = 6.25
      and 3.13 ug/mL, respectively, with SI > 10). N-(5-Chloropyrazin-2-ylbenzamides
      with hydroxy substitution (2b: R2 = 2-OH; 2d: R2 = 4-OH) on the benzene ring or
      their acetylated synthetic precursors possessed the broadest spectrum of
      activity, being active in all three groups of mycobacterial, bacterial and fungal
      strains. The substantial differences in in silico calculated properties (hydrogen
      bond pattern analysis, molecular electrostatic potential, HOMO and LUMO) can
      justify the differences in biological activities between N-pyrazinylbenzamides
      and N-phenylpyrazine-2-carboxamides.

PMID- 30231543
TI  - Phase I Study of Carbon Ion Radiotherapy and Image-Guided Brachytherapy for
      Locally Advanced Cervical Cancer.
AB  - A phase I study was performed to determine the recommended dose of carbon ion
      radiotherapy and 3D image-guided brachytherapy for histologically confirmed stage
      II (>=4 cm), III, or IVA cervical cancer. Dose-limiting toxicities (treatment
      related toxicities occurring within three months from the start of carbon ion
      radiotherapy) included Grade 3 non-hematological toxicity, Grade 4 hematological
      toxicity, or interruption of treatment for more than two weeks due to treatment
      related toxicities. Carbon ion radiotherapy consisted of whole-pelvic irradiation
      with 36.0 Gy (relative biological effectiveness) in 12 fractions and local boost
      with 19.2 Gy in four fractions for the primary site, and for positive lymph
      nodes. Three sessions of three-dimensional (3D) image-guided brachytherapy were
      administered after completion of carbon ion radiotherapy. Weekly cisplatin at a
      dose of 40 mg/m2 was given concurrently. At a dose level of one, a total
      rectosigmoid D2cc dose between 67.2 Gy and 71.3 Gy at a biological equivalent
      dose of 2 Gy per fraction from carbon ion radiotherapy and 3D image-guided
      brachytherapy was prescribed. Six patients were enrolled into this dose level. No
      patients developed the pre-defined dose-limiting toxicities. For late toxicities,
      however, one patient developed Grade 3 rectal hemorrhage requiring transfusion at
      10 months after treatment. The median survival time was 50.0 months for the five
      surviving patients. No further dose escalation was performed, and we determined
      the dose of level one as the recommended rectosigmoid dose. Although our results
      are preliminary, the study regimen encourages further investigation
      (registration: UMIN000013340).

PMID- 30231545
TI  - Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in
      Mice.
AB  - Protein O-linked beta-N-acetylglucosamine glycosylation (O-GlcNAcylation)
      regulates many biological processes. Studies have shown that O-GlcNAc
      modification levels can increase during acute stress and suggested that this may
      contribute to the survival of the cell. This study investigated the possible
      effects of O-GlcNAcylation that regulate glucose metabolism, apoptosis, and
      autophagy in the liver after acute cold stress. Male C57BL/6 mice were exposed to
      cold conditions (4  degrees C) for 0, 2, 4, and 6 h, then their livers were
      extracted and the expression of proteins involved in glucose metabolism,
      apoptosis, and autophagy was determined. It was found that acute cold stress
      increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation
      levels. This was accompanied by significantly increased activation levels of the
      glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2
      kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3beta
      (GSK3beta). The levels of glycolytic intermediates, fructose-1,6-diphosphate
      (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a
      sharp decrease. Additionally, adenosine triphosphate (ATP), as the main cellular
      energy source, had a sharp increase. Furthermore, the B-cell lymphoma 2(Bcl
      2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine
      aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were
      reduced after acute cold stress. Therefore, acute cold stress was found to
      increase O-GlcNAc modification levels, which may have resulted in the decrease of
      the essential processes of apoptosis and autophagy, promoting cell survival,
      while altering glycose transport, glycogen synthesis, and glycolysis in the
      liver.

PMID- 30231547
TI  - Performance Evaluation Strategies for Eye Gaze Estimation Systems with
      Quantitative Metrics and Visualizations.
AB  - An eye tracker's accuracy and system behavior play critical roles in determining
      the reliability and usability of eye gaze data obtained from them. However, in
      contemporary eye gaze research, there exists a lot of ambiguity in the
      definitions of gaze estimation accuracy parameters and lack of well-defined
      methods for evaluating the performance of eye tracking systems. In this paper, a
      set of fully defined evaluation metrics are therefore developed and presented for
      complete performance characterization of generic commercial eye trackers, when
      they operate under varying conditions on desktop or mobile platforms. In
      addition, some useful visualization methods are implemented, which will help in
      studying the performance and data quality of eye trackers irrespective of their
      design principles and application areas. Also the concept of a graphical user
      interface software named GazeVisual v1.1 is proposed that would integrate all
      these methods and enable general users to effortlessly access the described
      metrics, generate visualizations and extract valuable information from their own
      gaze datasets. We intend to present these tools as open resources in future to
      the eye gaze research community for use and further advancement, as a
      contribution towards standardization of gaze research outputs and analysis.

PMID- 30231546
TI  - Increased Oral Bioavailability of Resveratrol by Its Encapsulation in Casein
      Nanoparticles.
AB  - Resveratrol is a naturally occurring polyphenol that provides several health
      benefits including cardioprotection and cancer prevention. However, its
      biological activity is limited by a poor bioavailability when taken orally. The
      aim of this work was to evaluate the capability of casein nanoparticles as oral
      carriers for resveratrol. Nanoparticles were prepared by a coacervation process,
      purified and dried by spray-drying. The mean size of nanoparticles was around 200
      nm with a resveratrol payload close to 30 MUg/mg nanoparticle. In vitro studies
      demonstrated that the resveratrol release from casein nanoparticles was not
      affected by the pH conditions and followed a zero-order kinetic. When
      nanoparticles were administered orally to rats, they remained within the gut,
      displaying an important capability to reach the intestinal epithelium. No
      evidence of nanoparticle "translocation" were observed. The resveratrol plasma
      levels were high and sustained for at least 8 h with a similar profile to that
      observed for the presence of the major metabolite in plasma. The oral
      bioavailability of resveratrol when loaded in casein nanoparticles was calculated
      to be 26.5%, 10 times higher than when the polyphenol was administered as oral
      solution. Finally, a good correlation between in vitro and in vivo data was
      observed.

PMID- 30231548
TI  - Analysis of Angiotensin Converting Enzyme, Endothelial Nitric Oxide Synthase &
      Serotonin Gene Polymorphisms among Atrial Septal Defect Subjects with and without
      Pulmonary Arterial Hypertension.
AB  - Genetic polymorphisms are variations in DNA sequences which can influence either
      disease susceptibility, severity, or prognosis. Pulmonary arterial hypertension
      (PAH) is one of the complications that occurs in certain patients who have atrial
      septal defect (ASD). This study seeks to determine the association of gene
      polymorphisms with the pathogenesis of PAH in ASD patients. This study was
      conducted on 30 ASD patients with PAH, and 50 ASD patients who were not diagnosed
      with PAH. All respondents were Malay. Patients were selected based on stringent
      inclusion and exclusion criteria. Molecular analyses were done to detect the
      genetic polymorphisms of angiotensin converting enzyme (ACE I/D), serotonin
      transporter (5-HTTLPR), endothelial nitric oxide synthase (eNOS) G894T, and eNOS
      4b/4a. The genotypes of these genetic polymorphisms were determined using
      conventional PCR and PCR-RFLP methods. The PCR products were analysed using
      agarose gel electrophoresis. Statistical analysis was done using SPSS Version 22.
      Clinical characteristics, such as the diameter of ASD, mean arterial pressure
      (MAP), and mean pulmonary artery pressure (mPAP) differed significantly (p <
      0.05). Based on the statistical analysis, ACE I/D, eNOS G894T, and eNOS 4b/4a do
      not contribute to the progression of PAH amongst ASD patients (p > 0.05).
      However, the L allele of the 5-HTTLPR gene polymorphism may have an affect on the
      development of PAH in ASD patients (p < 0.05).

PMID- 30231549
TI  - Effect of CO2 Partial Pressure on the Corrosion Behavior of J55 Carbon Steel in
      30% Crude Oil/Brine Mixture.
AB  - The influence of CO2 partial pressure on the corrosion properties, including
      corrosion rate, morphology, chemical composition, and corrosion depth, of J55
      carbon steel in 30% crude oil/brine at 65  degrees C was investigated. A
      corrosion mechanism was then proposed based on the understanding of the formation
      of localized corrosion. Results showed that localized corrosion occurred in 30%
      crude oil/brine with CO2. The corrosion rate sharply increased as the CO2 partial
      pressure (P co 2 ) was increased from 0 to 1.5 MPa, decreased from P co 2 = 1.5
      MPa to P co 2 = 5.0 MPa, increased again at P co 2 = 5.0 MPa, and then reached a
      constant value after P co 2 = 9.0 MPa. The system pH initially decreased, rapidly
      increased, and then stabilized as CO2 partial pressure was increased. In the
      initial period, the surface of J55 carbon steel in the CO2/30% crude oil/brine
      mixtures showed intense corrosion. In conclusion, CO2 partial pressure affects
      the protection performance of FeCO3 by changing the formation of corrosion scale
      and further affecting the corrosion rate.

PMID- 30231550
TI  - A Hybrid Deep Learning Model for Predicting Protein Hydroxylation Sites.
AB  - Protein hydroxylation is one type of post-translational modifications (PTMs)
      playing critical roles in human diseases. It is known that protein sequence
      contains many uncharacterized residues of proline and lysine. The question that
      needs to be answered is: which residue can be hydroxylated, and which one cannot.
      The answer will not only help understand the mechanism of hydroxylation but can
      also benefit the development of new drugs. In this paper, we proposed a novel
      approach for predicting hydroxylation using a hybrid deep learning model
      integrating the convolutional neural network (CNN) and long short-term memory
      network (LSTM). We employed a pseudo amino acid composition (PseAAC) method to
      construct valid benchmark datasets based on a sliding window strategy and used
      the position-specific scoring matrix (PSSM) to represent samples as inputs to the
      deep learning model. In addition, we compared our method with popular predictors
      including CNN, iHyd-PseAAC, and iHyd-PseCp. The results for 5-fold cross
      validations all demonstrated that our method significantly outperforms the other
      methods in prediction accuracy.

PMID- 30231551
TI  - Breakfast Consumption in Spain: Patterns, Nutrient Intake and Quality. Findings
      from the ANIBES Study, a Study from the International Breakfast Research
      Initiative.
AB  - This study aimed to investigate energy, nutrient and food group intakes at
      breakfast in Spain and to examine for the first time, their relationship to the
      overall Diet Quality (DQ). The data used were from the Spanish ANIBES
      (anthropometric data, macronutrients and micronutrients intake, practice of
      physical activity, socioeconomic data and lifestyles in Spain), a cross-sectional
      study using a nationally representative sample of the Spanish population (9-75
      years old). DQ was assessed using the Nutrient Rich Foods Index, adapted to total
      diets (NRF9.3d). Most (>85%) of the Spanish population were regular breakfast
      consumers, although one in five adolescents were breakfast skippers. Breakfast
      provides just 16-19% of the daily intake of energy. Relative to its daily energy
      contribution, the Spanish breakfast contributed a higher proportion of daily
      total carbohydrates, added sugars, sodium, thiamin, riboflavin, folates, iron,
      potassium, magnesium, phosphorus and especially in calcium. By contrast, the
      breakfast is low in water intake, protein, dietary fibre, total fat,
      polyunsaturated fatty acids, beta-carotene and vitamins E and D. In children and
      teenagers, the most commonly consumed breakfast food was chocolate (mainly as
      chocolate-flavoured milk and powder), followed by bakery and pastry, whole milk
      and semi-skimmed milk. In the older groups, a bigger variety of foods were
      reported. Consumers in the highest NRF9.3d tertile for diet quality tended to
      have a higher intake of positive nutrients at breakfast than other tertiles, most
      notably among adults.

PMID- 30231552
TI  - Innovative Extraction Techniques and Hyphenated Instrument Configuration for
      Complex Matrices Analysis.

PMID- 30231553
TI  - STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context.
AB  - Signal transducer and activator of transcription 3 (STAT3) is responsible for
      mediating the transcriptional programs downstream of several cytokine, growth
      factor, and oncogenic stimuli. Its expression and activity are consistently
      linked to cellular transformation, as well as tumor initiation and progression.
      Due to this central role, STAT3 is widely considered a good target for anti
      cancer therapy; however, the success of these approaches has been, so far, very
      limited. Notably, on one side, STAT3 is aberrantly active in many breast cancers,
      on the other, at the physiological level, it is the main mediator of epithelial
      cell death during post-lactation mammary-gland involution, thus strongly
      suggesting that its biological functions are highly context-specific. One of the
      most peculiar features of STAT3 is that it can act both in cell-autonomous and
      non-cell-autonomous manners, simultaneously modulating the phenotypes of the
      tumor cells and their microenvironment. Here, we focus on the role of STAT3 in
      breast cancer progression, discussing the potential contrasting roles of STAT3
      activation in the establishment of locally recurrent and distant metastatic
      disease. Based on the most recent literature, depending on the tumor cell type,
      the local microenvironment status, and the stage of the disease, either STAT3
      activation or inactivation can support disease progression. Accordingly, cancer
      cells dynamically exploit STAT3 activity to carry out transcriptional programs
      somehow contrasting and complementary, such as supporting survival and growth,
      dormancy and awakening, stem cell-like features, and inflammation, immune
      response, and immune evasion. As a consequence, to achieve clinical efficacy, the
      conception and testing of anti-STAT3 targeted therapies will need a very careful
      evaluation of these opposing roles and of the most appropriate tumor context,
      disease stage and patient population to treat.

PMID- 30231554
TI  - The Streptococcus pneumoniaeyefM-yoeB and relBE Toxin-Antitoxin Operons
      Participate in Oxidative Stress and Biofilm Formation.
AB  - Type II (proteic) toxin-antitoxin systems (TAs) are widely distributed among
      bacteria and archaea. They are generally organized as operons integrated by two
      genes, the first encoding the antitoxin that binds to its cognate toxin to
      generate a harmless protein-protein complex. Under stress conditions, the
      unstable antitoxin is degraded by host proteases, releasing the toxin to achieve
      its toxic effect. In the Gram-positive pathogen Streptococcus pneumoniae we have
      characterized four TAs: pezAT, relBE, yefM-yoeB, and phD-doc, although the latter
      is missing in strain R6. We have assessed the role of the two yefM-yoeB and relBE
      systems encoded by S. pneumoniae R6 by construction of isogenic strains lacking
      one or two of the operons, and by complementation assays. We have analyzed the
      phenotypes of the wild type and mutants in terms of cell growth, response to
      environmental stress, and ability to generate biofilms. Compared to the wild
      type, the mutants exhibited lower resistance to oxidative stress. Further,
      strains deleted in yefM-yoeB and the double mutant lacking yefM-yoeB and relBE
      exhibited a significant reduction in their ability for biofilm formation.
      Complementation assays showed that defective phenotypes were restored to wild
      type levels. We conclude that these two loci may play a relevant role in these
      aspects of the S. pneumoniae lifestyle and contribute to the bacterial
      colonization of new niches.

PMID- 30231555
TI  - Exfoliation and Characterization of V2Se9 Atomic Crystals.
AB  - Mass production of one-dimensional, V2Se9 crystals, was successfully synthesized
      using the solid-state reaction of vanadium and selenium. Through the mechanical
      exfoliation method, the bulk V2Se9 crystal was easily separated to nanoribbon
      structure and we have confirmed that as-grown V2Se9 crystals consist of
      innumerable single V2Se9 chains linked by van der Waals interaction. The
      exfoliated V2Se9 flakes can be controlled thickness by the repeated-peeling
      method. In addition, atomic thick nanoribbon structure of V2Se9 was also obtained
      on a 300 nm SiO2/Si substrate. Scanning Kelvin probe microscopy analysis was used
      to explore the variation of work function depending on the thickness of V2Se9
      flakes. We believe that these observations will be of great help in selecting
      suitable metal contacts for V2Se9 and that a V2Se9 crystal is expected to have an
      important role in future nano-electronic devices.

PMID- 30231557
TI  - A Bayesian Quantile Modeling for Spatiotemporal Relative Risk: An Application to
      Adverse Risk Detection of Respiratory Diseases in South Carolina, USA.
AB  - Quantile modeling has been seen as an alternative and useful complement to
      ordinary regression mainly focusing on the mean. To directly apply quantile
      modeling to areal data the discrete conditional quantile function of the data can
      be an issue. Although jittering by adding a small number from a uniform
      distribution to impose pseudo-continuity has been proposed, the approach can have
      a great influence on responses with small values. Thus we proposed an alternative
      to model the quantiles of relative risk for spatiotemporal areal health data
      within a Bayesian framework using the log-Laplace distribution. A simulation
      study was conducted to assess the performance of the proposed method and examine
      whether the model could robustly estimate quantiles of spatiotemporal count data.
      To perform a test with a real data example, we evaluated the potential
      application of clustering under the proposed log-Laplace and mean regression. The
      data were obtained from the total number of emergency room discharges for
      respiratory conditions, both infectious and non-infectious diseases, in the U.S.
      state of South Carolina in 2009. From both simulation and case studies, the
      proposed quantile modeling demonstrated potential for broad applicability in
      various areas of spatial health studies including anomaly detection.

PMID- 30231556
TI  - A Mini Review Focused on the Recent Applications of Graphene Oxide in Stem Cell
      Growth and Differentiation.
AB  - Stem cells are undifferentiated cells that can give rise to any types of cells in
      our body. Hence, they have been utilized for various applications, such as drug
      testing and disease modeling. However, for the successful of those applications,
      the survival and differentiation of stem cells into specialized lineages should
      be well controlled. Growth factors and chemical agents are the most common
      signals to promote the proliferation and differentiation of stem cells. However,
      those approaches holds several drawbacks such as the negative side effects,
      degradation or denaturation, and expensive. To address such limitations,
      nanomaterials have been recently used as a better approach for controlling stem
      cells behaviors. Graphene oxide is the derivative of graphene, the first two
      dimensional (2D) materials in the world. Recently, due to its extraordinary
      properties and great biological effects on stem cells, many scientists around the
      world have utilized graphene oxide to enhance the differentiation potential of
      stem cells. In this mini review, we highlight the key advances about the effects
      of graphene oxide on controlling stem cell growth and various types of stem cell
      differentiation. We also discuss the possible molecular mechanisms of graphene
      oxide in controlling stem cell growth and differentiation.

PMID- 30231558
TI  - The Epidemiology of Food Allergy in the Global Context.
AB  - There is a lack of high-quality evidence based on the gold standard of oral food
      challenges to determine food allergy prevalence. Nevertheless, studies using
      surrogate measures of food allergy, such as health service utilization and
      clinical history, together with allergen-specific immunoglobulin E (sIgE),
      provide compelling data that the prevalence of food allergy is increasing in both
      Western and developing countries. In Western countries, challenge-diagnosed food
      allergy has been reported to be as high as 10%, with the greatest prevalence
      noted among younger children. There is also growing evidence of increasing
      prevalence in developing countries, with rates of challenge-diagnosed food
      allergy in China and Africa reported to be similar to that in Western countries.
      An interesting observation is that children of East Asian or African descent born
      in a Western environment are at higher risk of food allergy compared to Caucasian
      children; this intriguing finding emphasizes the importance of genome-environment
      interactions and forecasts future increases in food allergy in Asia and Africa as
      economic growth continues in these regions. While cow's milk and egg allergy are
      two of the most common food allergies in most countries, diverse patterns of food
      allergy can be observed in individual geographic regions determined by each
      country's feeding patterns. More robust studies investigating food allergy
      prevalence, particularly in Asia and the developing world, are necessary to
      understand the extent of the food allergy problem and identify preventive
      strategies to cope with the potential increase in these regions.

PMID- 30231559
TI  - A Brief Review of Personality in Marathon Runners: The Role of Sex, Age and
      Performance Level.
AB  - The participation of recreational runners in sport events ranging from 5 km to
      ultra-endurance races have increased dramatically during the last decades and
      this phenomenon has attracted scientific interest. Most research has focused on
      the physiological characteristics of these runners and less in their
      psychological characteristics. Therefore, the aim of the present study was to
      review the existing knowledge with regards to the personality of recreational
      endurance runners and the role of sex, age and performance. It was concluded that
      limited information was available with regards to the personality of recreational
      marathon runners. So far, our knowledge on the personality of marathon runners
      relied on studies conducted a few decades ago, mostly on competitive marathon
      runners, highlighting the need for original research on recreational runners.

PMID- 30231560
TI  - Caerin1.1 Suppresses the Growth of Porcine Epidemic Diarrhea Virus In Vitro via
      Direct Binding to the Virus.
AB  - Porcine epidemic diarrhea (PED) has re-emerged in recent years and has already
      caused huge economic losses to the porcine industry all over the world.
      Therefore, it is urgent for us to find out efficient ways to prevent and control
      this disease. In this study, the antiviral activity of a cationic amphibian
      antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV)
      was evaluated by an in vitro system using Vero cells. We found that even at a
      very low concentration, Caerin1.1 has the ability to destroy the integrity of the
      virus particles to block the release of the viruses, resulting in a considerable
      decrease in PEDV infections. In addition, Caerin1.1 showed powerful antiviral
      activity without interfering with the binding progress between PEDV and the
      receptor of the cells, therefore, it could be used as a potential antiviral drug
      or as a microbicide compound for prevention and control of PEDV.

PMID- 30231562
TI  - Short-Term and Long-Term Effects of Off-Job Activities on Recovery and Sleep: A
      Two-Wave Panel Study among Health Care Employees.
AB  - This study examined whether particular recovery activities after work have a
      positive or negative effect on employee recovery from work (i.e., cognitive,
      emotional, and physical detachment) and sleep quality. We used a two-wave panel
      study of 230 health care employees which enabled looking at both short-term and
      long-term effects (i.e., two-year time interval). Gender, age, marital status,
      children at home, education level, management position, and working hours were
      used as control variables. Hierarchical multiple regression analyses showed that
      work-related off-job activities were negatively associated with cognitive and
      emotional detachment in both the short and long run, whereas low-effort off-job
      activities were positively related to cognitive detachment in the short run.
      Moreover, household/care off-job activities were positively related to sleep
      quality in the long run, whereas physical off-job activities were negatively
      associated with sleep quality in the long run. The long-term findings existed
      beyond the strong effects of baseline detachment and sleep quality. This study
      highlights the importance of off-job recovery activities for health care
      employees' detachment from work and sleep quality. Practical implications and
      avenues for further research are discussed.

PMID- 30231563
TI  - Experimental Investigation of Compression Properties of Composites with Printed
      Braiding Structure.
AB  - A kind of composite was designed and additive manufacturing (AM) technology was
      utilized in the braiding structure fabrication. The printed polylactic acid (PLA)
      braiding structures were integrated with two types of resins (Epon 828 resin and
      urethane dimethacrylate/triethylene glycol dimethacrylate (UDMA/TEDGMA) resin)
      used as the matrix to make composite specimens. The compression test of the
      composite specimens showed that the printed PLA braiding structures had the
      effect of varying the compression properties of pure resins: it decreased the
      compression properties of Epon 828 resin, but increased those of UDMA/TEGDMA
      resin. Observing scanning electron microscope (SEM) images, it was noted that the
      decreasing and increasing in the compression properties of the specimens were
      related to the bonding compactness between the printed braiding structure and
      resins. Our results may suggest a new methods for the fast manufacturing of AM
      based composites, further research directions, and potential applications of this
      kind of composites.

PMID- 30231561
TI  - Current Immunotherapeutic Approaches in T Cell Non-Hodgkin Lymphomas.
AB  - T cell non-Hodgkin lymphoma (T-NHL) is a rare and heterogeneous group of
      neoplasms of the lymphoid system. With the exception of a few relatively indolent
      entities, T-NHL is typically aggressive, treatment resistant, and associated with
      poor prognosis. Relatively few options with proven clinical benefit are available
      for patients with relapsed or refractory disease. Immunotherapy has emerged as a
      promising treatment for the management of patients with hematological
      malignancies. The identification of tumor antigens has provided a large number of
      potential targets. Therefore, several monoclonal antibodies (alemtuzumab, SGN-30,
      brentuximab vedotin, and mogamulizumab), directed against tumor antigens, have
      been investigated in different subtypes of T-NHL. In addition to targeting
      antigens involved in cancer cell physiology, antibodies can stimulate immune
      effector functions or counteract immunosuppressive mechanisms. Chimeric antigen
      receptor (CAR)-T cells directed against CD30 and immune checkpoint inhibitors are
      currently being investigated in clinical trials. In this review, we summarize the
      currently available clinical evidence for immunotherapy in T-NHL, focusing on the
      results of clinical trials using first generation monoclonal antibodies, new
      immunotherapeutic agents, immune checkpoint inhibitors, and CAR-T cell therapies.

PMID- 30231565
TI  - Let's Talk about TEX-Understanding Consumer Preferences for Smart Interactive
      Textile Products Using a Conjoint Analysis Approach.
AB  - Interactive textiles are reaching maturity. First technology augmented textiles
      in form of clothes and furnitures are becoming commercially available. In
      contrast to the close link between technological development and innovations,
      future users' acceptance and usage of such interactive textiles has not been
      integrated sufficiently, yet. The current study investigates future users'
      consumer behavior and acceptance of interactive textiles using a scenario-based
      conjoint analysis study, which was presented in an online questionnaire ( n = 324
      ). Two prototypical interactive textiles were focused on: a smart jacket and a
      smart armchair. To assess the textile products, the participants had to choose
      the preferred product alternative consisting each of the acceptance-relevant
      factors "connectivity", "input modality", "feature range", "usability", and "ease
      of cleaning"and their respective levels. The results revealed that the "ease of
      cleaning" is the most important decision criterion for both textile devices (even
      more important for the smart jacket), followed by "feature range",
      "connectivity", and "usability". In contrast, the "input modality" is perceived
      as least important. The study also identified user profiles based on the
      projected consumer behavior ("adopters", "rejecters", and "undecided") for both
      products. Besides the differences in product evaluation and projected consumer
      behavior, the user groups are significantly influenced by the individual affinity
      to textiles (both products) and gender (smart jacket). The findings are used to
      derive design and communication guidelines referring to interactive textiles in
      order to incorporate users' needs, wishes, and requirements into future products.

PMID- 30231566
TI  - Surface Properties of SnO2 Nanowires Deposited on Si Substrate Covered by Au
      Catalyst Studies by XPS, TDS and SEM.
AB  - The surface chemistry and the morphology of SnO2 nanowires of average length and
      diameter of several um and around 100 nm, respectively, deposited by vapor phase
      deposition (VPD) method on Au-covered Si substrate, were studied before and after
      subsequent air exposure. For this purpose, surface-sensitive methods, including X
      ray photoelectron spectroscopy (XPS), thermal desorption spectroscopy (TDS) and
      the scanning electron microscopy (SEM), were applied. The studies presented
      within this paper allowed to determine their surface non-stoichiometry combined
      with the presence of carbon contaminations, in a good correlation with their
      surface morphology. The relative concentrations of the main components [O]/[Sn];
      [C]/[Sn]; [Au]/[Sn], together with the O-Sn; O-Si bonds, were analyzed. The
      results of TDS remained in a good agreement with the observations from XPS.
      Moreover, conclusions obtained for SnO2 nanowires deposited with the use of Au
      catalyst were compared to the previous obtained for Ag-assisted tin dioxide
      nanowires. The information obtained within these studies is of a great importance
      for the potential application of SnO2 nanowires in the field of novel chemical
      nanosensor devices, since the results can provide an interpretation of how aging
      effects influence gas sensor dynamic characteristics.

PMID- 30231564
TI  - Oxidative Phosphorylation: A Target for Novel Therapeutic Strategies Against
      Ovarian Cancer.
AB  - Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is
      growing evidence that oxidative phosphorylation is also an active metabolic
      pathway in many tumors, including in high grade serous ovarian cancer.
      Metastasized ovarian tumors use fatty acids for their energy needs. There is also
      evidence of ovarian cancer stem cells privileging oxidative phosphorylation
      (OXPHOS) for their metabolic needs. Metformin and thiazolidinediones such as
      rosiglitazone restrict tumor growth by inhibiting specific steps in the
      mitochondrial electron transport chain. These observations suggest that
      strategies to interfere with oxidative phosphorylation should be considered for
      the treatment of ovarian tumors. Here, we review the literature that supports
      this hypothesis and describe potential agents and critical control points in the
      oxidative phosphorylation pathway that can be targeted using small molecule
      agents. In this review, we also discuss potential barriers that can reduce the
      efficacy of the inhibitors of oxidative phosphorylation.

PMID- 30231568
TI  - Extra Surfactant-Assisted Self-Assembly of Highly Ordered Monolayers of BaTiO3
      Nanocubes at the Air-Water Interface.
AB  - Assembly of nanocrystals into ordered two- or three-dimensional arrays is an
      essential technology to achieve their application in novel functional devices.
      Among a variety of assembly techniques, evaporation-induced self-assembly (EISA)
      is one of the prospective approaches because of its simplicity. Although EISA has
      shown its potential to form highly ordered nanocrystal arrays, the formation of
      uniform nanocrystal arrays over large areas remains a challenging subject. Here,
      we introduce a new EISA method and demonstrate the formation of large-scale
      highly ordered monolayers of barium titanate (BaTiO3, BT) nanocubes at the air
      water interface. In our method, the addition of an extra surfactant to a water
      surface assists the EISA of BT nanocubes with a size of 15-20 nm into a highly
      ordered arrangement. We reveal that the compression pressure exerted by the extra
      surfactant on BT nanocubes during the solvent evaporation is a key factor in the
      self-assembly in our method. The BT nanocube monolayers transferred to substrates
      have sizes up to the millimeter scale and a high out-of-plane crystal
      orientation, containing almost no microcracks and voids.

PMID- 30231569
TI  - Nitric Oxide Enhancing Resistance to PEG-Induced Water Deficiency is Associated
      with the Primary Photosynthesis Reaction in Triticum aestivum L.
AB  - Photosynthesis is affected by water-deficiency (WD) stress, and nitric oxide (NO)
      is a free radical that participates in the photosynthesis process. Previous
      studies have suggested that NO regulates excitation-energy distribution of
      photosynthesis under WD stress. Here, quantitative phosphoproteomic profiling was
      conducted using iTRAQ. Differentially phosphorylated protein species (DEPs) were
      identified in leaves of NO- or polyethylene glycol (PEG)-treated wheat seedlings
      (D), and in control seedlings. From 1396 unique phosphoproteins, 2257 unique
      phosphorylated peptides and 2416 phosphorylation sites were identified. Of these,
      96 DEPs displayed significant changes (>=1.50-fold, p < 0.01). These DEPs are
      involved in photosynthesis, signal transduction, etc. Furthermore,
      phosphorylation of several DEPs was upregulated by both D and NO treatments, but
      downregulated only in NO treatment. These differences affected the chlorophyll A
      B binding protein, chloroplast post-illumination chlorophyll-fluorescence
      increase protein, and SNT7, implying that NO indirectly regulated the absorption
      and transport of light energy in photosynthesis in response to WD stress. The
      significant difference of chlorophyll (Chl) content, Chl a fluorescence
      transient, photosynthesis index, and trapping and transport of light energy
      further indicated that exogenous NO under D stress enhanced the primary
      photosynthesis reaction compared to D treatment. A putative pathway is proposed
      to elucidate NO regulation of the primary reaction of photosynthesis under WD.

PMID- 30231567
TI  - Treatment Strategies for Infected Wounds.
AB  - The treatment of skin wounds is a key research domain owing to the important
      functional and aesthetic role of this tissue. When the skin is impaired, bacteria
      can soon infiltrate into underlying tissues which can lead to life-threatening
      infections. Consequently, effective treatments are necessary to deal with such
      pathological conditions. Recently, wound dressings loaded with antimicrobial
      agents have emerged as viable options to reduce wound bacterial colonization and
      infection, in order to improve the healing process. In this paper, we present an
      overview of the most prominent antibiotic-embedded wound dressings, as well as
      the limitations of their use. A promising, but still an underrated group of
      potential antibacterial agents that can be integrated into wound dressings are
      natural products, especially essential oils. Some of the most commonly used
      essential oils against multidrug-resistant microorganisms, such as tea tree, St.
      John's Wort, lavender and oregano, together with their incorporation into wound
      dressings are presented. In addition, another natural product that exhibits
      encouraging antibacterial activity is honey. We highlight recent results of
      several studies carried out by researchers from different regions of the world on
      wound dressings impregnated with honey, with a special emphasis on Manuka honey.
      Finally, we highlight recent advances in using nanoparticles as platforms to
      increase the effect of pharmaceutical formulations aimed at wound healing.
      Silver, gold, and zinc nanoparticles alone or functionalized with diverse
      antimicrobial compounds have been integrated into wound dressings and
      demonstrated therapeutic effects on wounds.

PMID- 30231570
TI  - Soluble Toll-Like Receptor 4 Impairs the Interaction of Shiga Toxin 2a with Human
      Serum Amyloid P Component.
AB  - Shiga toxin 2a (Stx2a) is the main virulence factor produced by pathogenic
      Escherichia coli strains (Stx-producing E. coli, STEC) responsible for
      hemorrhagic colitis and the life-threatening sequela hemolytic uremic syndrome in
      children. The toxin released in the intestine by STEC targets the
      globotriaosylceramide receptor (Gb3Cer) present on the endothelial cells of the
      brain and the kidney after a transient blood phase during which Stx2a interacts
      with blood components, such as neutrophils, which, conversely, recognize Stx
      through Toll-like receptor 4 (TLR4). Among non-cellular blood constituents, human
      amyloid P component (HuSAP) is considered a negative modulating factor that
      specifically binds Stx2a and impairs its toxic action. Here, we show that the
      soluble extracellular domain of TLR4 inhibits the binding of Stx2a to
      neutrophils, assessed by indirect flow cytometric analysis. Moreover, by using
      human sensitive Gb3Cer-expressing cells (Raji cells) we found that the complex
      Stx2a/soluble TLR4 escaped from capture by HuSAP allowing the toxin to target and
      damage human cells, as assayed by measuring translation inhibition, the typical
      Stx-induced functional impairment. Thus, soluble TLR4 stood out as a positive
      modulating factor for Stx2a. In the paper, these findings have been discussed in
      the context of the pathogenesis of hemolytic uremic syndrome.

PMID- 30231571
TI  - Recent Advances in Fluorescent Probes for Lipid Droplets.
AB  - Lipid droplets (LDs) are organelles that serve as the storage of intracellular
      neutral lipids. LDs regulate many physiological processes. They recently
      attracted attention after extensive studies showed their involvement in metabolic
      disorders and diseases such as obesity, diabetes, and cancer. Therefore, it is of
      the highest importance to have reliable imaging tools. In this review, we focus
      on recent advances in the development of selective fluorescent probes for LDs.
      Their photophysical properties are described, and their advantages and drawbacks
      in fluorescence imaging are discussed. At last, we review the reported
      applications using these probes including two-photon excitation, in vivo and
      tissue imaging, as well as LDs tracking.

PMID- 30231574
TI  - Hyperspectral Image Classification with Capsule Network Using Limited Training
      Samples.
AB  - Deep learning techniques have boosted the performance of hyperspectral image
      (HSI) classification. In particular, convolutional neural networks (CNNs) have
      shown superior performance to that of the conventional machine learning
      algorithms. Recently, a novel type of neural networks called capsule networks
      (CapsNets) was presented to improve the most advanced CNNs. In this paper, we
      present a modified two-layer CapsNet with limited training samples for HSI
      classification, which is inspired by the comparability and simplicity of the
      shallower deep learning models. The presented CapsNet is trained using two real
      HSI datasets, i.e., the PaviaU (PU) and SalinasA datasets, representing complex
      and simple datasets, respectively, and which are used to investigate the
      robustness or representation of every model or classifier. In addition, a
      comparable paradigm of network architecture design has been proposed for the
      comparison of CNN and CapsNet. Experiments demonstrate that CapsNet shows better
      accuracy and convergence behavior for the complex data than the state-of-the-art
      CNN. For CapsNet using the PU dataset, the Kappa coefficient, overall accuracy,
      and average accuracy are 0.9456, 95.90%, and 96.27%, respectively, compared to
      the corresponding values yielded by CNN of 0.9345, 95.11%, and 95.63%. Moreover,
      we observed that CapsNet has much higher confidence for the predicted
      probabilities. Subsequently, this finding was analyzed and discussed with
      probability maps and uncertainty analysis. In terms of the existing literature,
      CapsNet provides promising results and explicit merits in comparison with CNN and
      two baseline classifiers, i.e., random forests (RFs) and support vector machines
      (SVMs).

PMID- 30231572
TI  - Functional Calcium Binding Peptides from Pacific Cod (Gadus macrocephalus) Bone:
      Calcium Bioavailability Enhancing Activity and Anti-Osteoporosis Effects in the
      Ovariectomy-Induced Osteoporosis Rat Model.
AB  - Calcium binding peptides from Pacific cod (Gadus macrocephalus) bone have
      attracted attention due to their potential effects on bone health. In this study,
      calcium binding peptides (CBP) were prepared from Pacific cod bone by trypsin and
      neutral protease. Ultraviolet spectra, circular dichroism (CD), and Fourier
      transform infrared spectroscopy (FTIR) revealed that carboxyl and amino groups in
      CBP could bind to Ca2+, and form the peptide-calcium complex (CBP-Ca). Single
      pass intestinal perfusion (SPIP) experiments indicated that the intestinal
      calcium absorption was significantly enhanced (p < 0.01) in CBP-Ca treated Wistar
      rats. The anti-osteoporosis activity of CBP-Ca was investigated in the
      ovariectomized (OVX) Wistar rat model. The administration of CBP-Ca significantly
      (p < 0.01) improved the calcium bioavailability, trabecular bone structure, bone
      biomechanical properties, bone mineral density, and bone mineralization degree.
      CBP-Ca notably (p < 0.01) increased serum calcium, however, it remarkably (p <
      0.01) reduced the levels of osteocalcin (OCN), bone alkaline phosphatase (BALP),
      tartrate-resistant acid phosphatase isoform 5b (TRAP5b), and C-telopeptide of
      type I collagen (CTX-1) in serum. Results suggested that the cod bone derived CBP
      could bind with calcium, improve the intestinal calcium absorption, calcium
      bioavailability, and serum calcium, then reduce the bone turnover rate, and thus
      ameliorate osteoporosis.

PMID- 30231573
TI  - Adverse Drug Reactions, Power, Harm Reduction, Regulation and the ADRe Profiles.
AB  - The power and influence of healthcare systems comes largely from the ability to
      prescribe efficacious medicine. However, medicine can sometimes cause harm rather
      than bring benefits. Systematically checking patients for the adverse effects of
      medicines, as listed in manufacturers' literature, would protect patients from
      iatrogenic harm, but this is rarely undertaken. We argue for the benefits of this
      approach using the example of the prescription of antipsychotics to older adults.
      Prescribing antipsychotics to control challenging behaviours associated with
      dementia is a controversial matter, and regulatory intervention is under
      discussion. Improved regulatory systems could protect against iatrogenic harm,
      such as over-sedation, falls, tremor, or drug-induced Parkinsonism. However,
      measuring the impact and outcomes of regulatory interventions has proved
      difficult, not least because there are rarely systematic records of all adverse
      effects of medicines. We indicate how regulatory initiatives to reduce
      antipsychotic prescribing can be supported by systematic monitoring and
      documentation of patients' signs and symptoms of putative adverse drug reactions.
      Monitoring documentation then provides the rationale and support for
      professionals' responses to identified problems. Longitudinal monitoring records
      would improve understanding of the impact and outcomes of adverse drug reactions
      (ADRs) on health and wellbeing, and the many costs of ADRs.

PMID- 30231575
TI  - A Paradigmatic Interplay between Human Cytomegalovirus and Host Immune System:
      Possible Involvement of Viral Antigen-Driven CD8+ T Cell Responses in Systemic
      Sclerosis.
AB  - Human cytomegalovirus (HCMV) is a highly prevalent opportunistic agent in the
      world population, which persists as a latent virus after a primary infection.
      Besides the well-established role of this agent causing severe diseases in
      immunocompromised individuals, more recently, HCMV has been evoked as a possible
      factor contributing to the pathogenesis of autoimmune diseases such as systemic
      sclerosis (SSc). The interplay between HCMV and immune surveillance is supposed
      to become unbalanced in SSc patients with expanded anti-HCMV immune responses,
      which are likely involved in the exacerbation of inflammatory processes. In this
      study, blood samples from a cohort of SSc patients vs. healthy subjects were
      tested for anti-HCMV immune responses (IgM, IgG antibodies, and T cells to
      peptide pools spanning the most immunogenic HCMV proteins). Statistically
      significant increase of HCMV-specific CD8+ T cell responses in SSc patients vs.
      healthy subjects was observed. Moreover, significantly greater HCMV-specific CD8+
      T cell responses were found in SSc patients with a longer disease duration and
      those with higher modified Rodnan skin scores. Given the known importance of T
      cells in the development of SSc and that this virus may contribute to chronic
      inflammatory diseases, these data support a relevant role of HCMV-specific CD8+ T
      cell responses in SSc pathogenesis.

PMID- 30231576
TI  - Estimating Vaccine-Driven Selection in Seasonal Influenza.
AB  - Vaccination could be an evolutionary pressure on seasonal influenza if vaccines
      reduce the transmission rates of some ("targeted") strains more than others. In
      theory, more vaccinated populations should have a lower prevalence of targeted
      strains compared to less vaccinated populations. We tested for vaccine-induced
      selection in influenza by comparing strain frequencies between more and less
      vaccinated human populations. We defined strains in three ways: first as
      influenza types and subtypes, next as lineages of type B, and finally as clades
      of influenza A/H3N2. We detected spatial differences partially consistent with
      vaccine use in the frequencies of subtypes and types and between the lineages of
      influenza B, suggesting that vaccines do not select strongly among all these
      phylogenetic groups at regional scales. We did detect a significantly greater
      frequency of an H3N2 clade with known vaccine escape mutations in more vaccinated
      countries during the 2014-2015 season, which is consistent with vaccine-driven
      selection within the H3N2 subtype. Overall, we find more support for vaccine
      driven selection when large differences in vaccine effectiveness suggest a strong
      effect size. Variation in surveillance practices across countries could obscure
      signals of selection, especially when strain-specific differences in vaccine
      effectiveness are small. Further examination of the influenza vaccine's
      evolutionary effects would benefit from improvements in epidemiological
      surveillance and reporting.

PMID- 30231577
TI  - Endometrial Stem Cells in Farm Animals: Potential Role in Uterine Physiology and
      Pathology.
AB  - The endometrium is an accessible source of mesenchymal stem cells. Most
      investigations of endometrial mesenchymal stem cells (eMSCs) have been conducted
      in humans. In animals, particularly in livestock, eMSC research is scarce. Such
      cells have been described in the bovine, ovine, caprine, porcine, and equine
      endometrium. Here we provide the state of the art of eMSCs in farm animals with a
      focus on the bovine species. In bovines, eMSCs have been identified during the
      phases of the estrous cycle, during which their functionality and the presence of
      eMSC-specific markers has been shown to change. Moreover, postpartum inflammation
      related to endometritis affects the presence and functionality of eMSCs, and
      prostaglandin E2 (PGE2) may be the mediator of such changes. We demonstrated that
      exposure to PGE2 in vitro modifies the transcriptomic profile of eMSCs, showing
      its potential role in the fate of stem cell activation, migration, and homing
      during pathological uterine inflammation in endometritis and in healthy puerperal
      endometrium. Farm animal research on eMSCs can be of great value in translational
      research for certain uterine pathologies and for immunomodulation of local
      responses to pathogens, hormones, and other substances. Further research is
      necessary in areas such as in vivo location of the niches and their
      immunomodulatory and anti-infective properties.

PMID- 30231579
TI  - The Non-Coding RNA Journal Club: Highlights on Recent Papers-6.
AB  - We are delighted to share with you our sixth Journal Club and highlight some of
      the most interesting papers published recently [...].

PMID- 30231578
TI  - Creatinine-Based Renal Function Estimates and Dosage of Postoperative Pain
      Management for Elderly Acute Hip Fracture Patients.
AB  - Many analgesics and their metabolites are renally excreted. The widely used
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-estimated glomerular
      filtration rate (eGFR) equations are not developed for use in the elderly, while
      the recent Berlin Initiative Study (BIS), Full Age Spectrum (FAS), and Lund-Malmo
      revised (LMR) equations are. This observational study investigated differences
      between creatinine-based eGFR equations and how the choice of equation influences
      dosage of analgesics in elderly (>=70 years) patients admitted with acute hip
      fracture. eGFR was calculated by the CKD-EPI, BIS, Cockcroft-Gault (CG), FAS,
      LMR, and Modification of Diet in Renal Disease (MDRD) equations. Standard daily
      dose for postoperative pain medications ibuprofen, morphine and gabapentin was
      simulated for each equation according to dosage recommendations in Renbase(r).
      For 118 patients, mean eGFR from the CKD-EPI, BIS, CG, FAS, LMR, and MDRD
      equations was 67.3 mL/min/1.73 m2, 59.1 mL/min/1.73 m2, 56.9 mL/min/1.73 m2, 60.3
      mL/min/1.73 m2, 58.9 mL/min/1.73 m2, and 79.1 mL/min/1.73 m2, respectively (p <
      0.0001). Mean difference to CKD-EPI was -10.4 mL/min/1.73 m2 to 11.8 mL/min/1.73
      m2. Choice of eGFR equation significantly influenced the recommended dose (p <
      0.0001). Shifting to BIS, FAS, or LMR equations led to a lower recommended dose
      in 20% to 31% of patients. Choice of eGFR equation significantly influenced
      dosing of ibuprofen, morphine, and gabapentin.

PMID- 30231581
TI  - Actinofuranones D-I from a Lichen-Associated Actinomycetes, Streptomyces
      gramineus, and Their Anti-Inflammatory Effects.
AB  - Six new metabolites, actinofuranones D-I (compounds 1-6), were isolated together
      with three known compounds-JBIR-108 (7), E-975 (8), and E-492 (9)-from a
      fermentation broth of Streptomyces gramineus derived from the lichen Leptogium
      trichophorum. The structures of the new compounds 1-6 were established using
      comprehensive NMR spectroscopic data analysis, as well as UV, IR, and MS data.
      The anti-inflammatory activity of these isolated compounds were evaluated by
      examining their ability to inhibit nitric oxide (NO) production in LPS-stimulated
      RAW 264.7 macrophage cells. Compounds 4, 5, 8, and 9 attenuated the production of
      NO due to the suppression of the expression of nitric oxide synthase (iNOS) in
      LPS-induced RAW 264.7 cells. Moreover, 4, 5, 8, and 9 also inhibited LPS-induced
      release of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis
      factor alpha (TNF-alpha).

PMID- 30231580
TI  - Passive Smoking Indicators in Italy: Does the Gross Domestic Product Matter?
AB  - BACKGROUND: The aim of this study is to analyse the correlation between regional
      values of Gross Domestic Product (GDP) and passive smoking in Italy. METHODS: The
      outcome measures were smoking ban respect in public places, workplaces and at
      home, derived from the PASSI surveillance for the period 2011-2017. The
      explanatory variable was GDP per capita. The statistical analysis was carried out
      using bivariate and linear regression analyses, taking into consideration two
      different periods, Years 2011-2014 and 2014-2017. RESULTS: GDP is showed to be
      positively correlated with smoking ban respect in public places (r = 0.779 p <
      0.001; r = 0.723 p < 0.001 in the two periods, respectively), as well as smoking
      ban respect in the workplace (r = 0.662 p = 0.001; r = 0.603 p = 0.004) and no
      smoking at home adherence (r = 0.424 p = 0.056; r = 0.362 p = 0.107). In multiple
      linear regression GDP is significantly associated to smoking ban respect in
      public places (adjusted beta = 0.730 p < 0.001; beta = 0.698 p < 0.001 in the two
      periods, respectively), smoking ban in workplaces (adjusted beta = 0.525 p =
      0.020; beta = 0.570 p = 0.009) and no smoking at home (adjusted beta = 0.332 p =
      0.070; beta = 0.362 p = 0.052). CONCLUSIONS: Smoking ban is more respected in
      Regions with higher GDP. For a better health promotion, systematic vigilance and
      sanctions should be maintained and strengthened, particularly in regions with low
      compliance with smoking bans.

PMID- 30231583
TI  - Phase Transformation and Morphology Evolution of Ti50Cu25Ni20Sn5 during
      Mechanical Milling.
AB  - Nanocrystalline/amorphous powder was produced by ball milling of Ti50Cu25Ni20Sn5
      (at.%) master alloy. Both laser diffraction particle size analyzer and scanning
      electron microscope (SEM) were used to monitor the changes in the particle size
      as well as in the shape of particles as a function of milling time. During ball
      milling, the average particle size decreased with milling time from >320 um to
      ~38 um after 180 min of milling. The deformation-induced hardening and phase
      transformation caused the hardness value to increase from 506 to 779 HV. X-ray
      diffraction (XRD) analysis was used to observe the changes in the
      phases/amorphous content as a function of milling time. The amount of amorphous
      fraction increased continuously until 120 min milling (36 wt % amorphous
      content). The interval of crystallite size was between 1 and 10 nm after 180 min
      of milling with 25 wt % amorphous fractions. Cubic Cu(Ni,Cu)Ti2 structure was
      transformed into the orthorhombic structure owing to the shear/stress,
      dislocations, and Cu substitution during the milling process.

PMID- 30231582
TI  - Nucleus, Mitochondrion, or Reticulum? STAT3 a La Carte.
AB  - The transcription factor signal transducer and activator of transcription (STAT)3
      mediates the functions of cytokines, growth factors, and oncogenes under both
      physiological and pathological conditions. Uncontrolled/constitutive STAT3
      activity is often detected in tumors of different types, where its role is mostly
      that of an oncogene, contributing in multiple ways to tumor transformation,
      growth, and progression. For this reason, many laboratories and pharmaceutical
      companies are making efforts to develop specific inhibitors. However, STAT3 has
      also been shown to act as a tumor suppressor in a number of cases, suggesting
      that its activity is strongly context-specific. Here, we discuss the bases that
      can explain the multiple roles of this factor in both physiological and
      pathological contexts. In particular, we focus on the following four features:
      (i) the distinct properties of the STAT3alpha and beta isoforms; (ii) the
      multiple post-translational modifications (phosphorylation on tyrosine or serine,
      acetylation and methylation on different residues, and oxidation and
      glutathionylation) that can affect its activities downstream of multiple
      different signals; (iii) the non-canonical functions in the mitochondria,
      contributing to the maintenance of energy homeostasis under stress conditions;
      and (iv) the recently discovered functions in the endoplasmic reticulum, where
      STAT3 contributes to the regulation of calcium homeostasis, energy production,
      and apoptosis.

PMID- 30231585
TI  - The Effect of Ultrasound, Oxygen and Sunlight on the Stability of (-)
      Epigallocatechin Gallate.
AB  - (-)-Epigallocatechin gallate (EGCG), is the main catechin found in green tea, and
      has several beneficial effects. This study investigated the stability of EGCG
      aqueous solution under different stored and ultrasonic conditions to determine
      whether it can be used with an ultrasonic dental scaler to treat periodontal
      infection. Four concentrations (0.05, 0.1, 0.15, 2 mg/mL) of EGCG aqueous
      solution were prepared and stored under four different conditions (A: Exposed to
      neither sunlight nor air, B: Exposed to sunlight, but not air, C: Not exposed to
      sunlight, but air, D: Exposed to sunlight and air) for two days. The degradation
      rate of EGCG was measured by high performance liquid chromatography (HPLC). On
      the other hand, an ultrasonic dental scaler was used to atomize the EGCG solution
      under four different conditions (a: Exposed to neither air nor sunlight, b: Not
      exposed to air, but sunlight, c: Not exposed to sunlight, but air, d: Exposed to
      air and sunlight), the degradation of EGCG was measured by HPLC. We found that
      the stability of EGCG was concentration-dependent in water at room temperature.
      Both sunlight and oxygen influenced the stability of EGCG, and oxygen had a more
      pronounced effect on stability of EGCG than sunlight. The most important
      conclusion was that the ultrasound may accelerate the degradation of EGCG due to
      the presence of oxygen and sunlight, but not because of the ultrasonic vibration.
      Thus, EGCG aqueous solution has the potential to be used through an ultrasonic
      dental scaler to treat periodontal infection in the future.

PMID- 30231584
TI  - Short Review on Porous Metal Membranes-Fabrication, Commercial Products, and
      Applications.
AB  - Porous metal membranes have recently received increasing attention, and
      significant progress has been made in their preparation and characterisation.
      This progress has stimulated research in their applications in a number of key
      industries including wastewater treatment, dairy processing, wineries, and
      biofuel purification. This review examines recent significant progress in porous
      metal membranes including novel fabrication concepts and applications that have
      been reported in open literature or obtained in our laboratories. The advantages
      and disadvantages of the different membrane fabrication methods were presented in
      light of improving the properties of current membrane materials for targeted
      applications. Sintering of particles is one of the main approaches that has been
      used for the fabrication of commercial porous metal membranes, and it has great
      advantages for the fabrication of hollow fibre metal membranes. However,
      sintering processes usually result in large pores (e.g., >1 um). So far, porous
      metal membranes have been mainly used for the filtration of liquids to remove the
      solid particles. For porous metal membranes to be more widely used across a
      number of separation applications, particularly for water applications, further
      work needs to focus on the development of smaller pore (e.g., sub-micron) metal
      membranes and the significant reduction of capital and maintenance costs.

PMID- 30231588
TI  - Air Pollutant and Health-Efficiency Evaluation Based on a Dynamic Network Data
      Envelopment Analysis.
AB  - Environmental pollution and the associated societal health issues have attracted
      recent research attention. While most research has focused on the effect of air
      pollution on human health and local economies, few articles have discussed the
      environment, health, and economic development in in an integrated analysis. This
      paper used a Dynamic Network SBM Model to evaluate production and health
      efficiencies in Chinese cities and found that the production efficiency scores
      were slightly higher than the health efficiency scores, with the two-stage
      efficiency scores in most cities having significant fluctuations. Labor, fixed
      assets, energy, GDP, and lung disease and mortality reduction efficiencies in the
      first stage were generally high; however, the medical input efficiencies in the
      second stage were low, indicating that there was there significant room for
      improvement in many cities.

PMID- 30231586
TI  - Monocytes and Macrophages as Viral Targets and Reservoirs.
AB  - Viruses manipulate cell biology to utilize monocytes/macrophages as vessels for
      dissemination, long-term persistence within tissues and virus replication.
      Viruses enter cells through endocytosis, phagocytosis, macropinocytosis or
      membrane fusion. These processes play important roles in the mechanisms
      contributing to the pathogenesis of these agents and in establishing viral genome
      persistence and latency. Upon viral infection, monocytes respond with an elevated
      expression of proinflammatory signalling molecules and antiviral responses, as is
      shown in the case of the influenza, Chikungunya, human herpes and Zika viruses.
      Human immunodeficiency virus initiates acute inflammation on site during the
      early stages of infection but there is a shift of M1 to M2 at the later stages of
      infection. Cytomegalovirus creates a balance between pro- and anti-inflammatory
      processes by inducing a specific phenotype within the M1/M2 continuum. Despite
      facilitating inflammation, infected macrophages generally display abolished
      apoptosis and restricted cytopathic effect, which sustains the virus production.
      The majority of viruses discussed in this review employ monocytes/macrophages as
      a repository but certain viruses use these cells for productive replication. This
      review focuses on viral adaptations to enter monocytes/macrophages, immune
      escape, reprogramming of infected cells and the response of the host cells.

PMID- 30231587
TI  - Magnetic Nanoparticles Applications for Amyloidosis Study and Detection: A
      Review.
AB  - Magnetic nanoparticles (MNPs) have great potential in biomedical and clinical
      applications because of their many unique properties. This contribution provides
      an overview of the MNPs mainly used in the field of amyloid diseases. The first
      part discusses their use in understanding the amyloid mechanisms of fibrillation,
      with emphasis on their ability to control aggregation of amyloidogenic proteins.
      The second part deals with the functionalization by various moieties of numerous
      MNPs' surfaces (molecules, peptides, antibody fragments, or whole antibodies of
      MNPs) for the detection and the quantification of amyloid aggregates. The last
      part of this review focuses on the use of MNPs for magnetic-resonance-based
      amyloid imaging in biomedical fields, with particular attention to the
      application of gadolinium-based paramagnetic nanoparticles (AGuIX), which have
      been recently developed. Biocompatible AGuIX nanoparticles show favorable
      characteristics for in vivo use, such as nanometric and straightforward
      functionalization. Their properties have enabled their application in MRI. Here,
      we report that AGuIX nanoparticles grafted with the Pittsburgh compound B can
      actively target amyloid aggregates in the brain, beyond the blood-brain barrier,
      and remain the first step in observing amyloid plaques in a mouse model of
      Alzheimer's disease.

PMID- 30231590
TI  - Pediatric Pleomorphic Adenoma of the Parotid: Case Report, Review of Literature
      and Novel Therapeutic Targets.
AB  - Salivary gland tumors are extremely rare and encompass a diverse group of
      histologies. Less than 5% of the affected population is pediatric. We present a
      case of 6-year-old child with pleomorphic adenoma of the parotid. The patient
      underwent a superficial parotidectomy. Recurrence was not observed in the six
      months of follow-up. Surgery is the mainstay of the management of benign salivary
      gland tumors. Although novel molecular agents are being explored, personalized
      therapy would be a challenge due to the rarity and vast genetic/histologic
      variations of salivary gland tumors.

PMID- 30231591
TI  - An Overview of the Focus of the International Gap Junction Conference 2017 and
      Future Perspectives.
AB  - This Special Issue relates to the 18th biannual International Gap Junction
      Conference (IGJC2017), held at the Crowne Plaza Hotel, Glasgow, U.K., from the 29
      July-2 August 2017 [...].

PMID- 30231589
TI  - Extracellular Vesicles in Bladder Cancer: Biomarkers and Beyond.
AB  - Tumor-derived extracellular vesicles (TEVs) are membrane-bound, nanosized
      vesicles released by cancer cells and taken up by cells in the tumor
      microenvironment to modulate the molecular makeup and behavior of recipient
      cells. In this report, we summarize the pivotal roles of TEVs involved in bladder
      cancer (BC) development, progression and treatment resistance through
      transferring their bioactive cargos, including proteins and nucleic acids. We
      also report on the molecular profiling of TEV cargos derived from urine and blood
      of BC patients as non-invasive disease biomarkers. The current hurdles in EV
      research and plausible solutions are discussed.

PMID- 30231593
TI  - Sub-Diffraction Visible Imaging Using Macroscopic Fourier Ptychography and
      Regularization by Denoising.
AB  - Imaging past the diffraction limit is of significance to an optical system.
      Fourier ptychography (FP) is a novel coherent imaging technique that can achieve
      this goal and it is widely used in microscopic imaging. Most phase retrieval
      algorithms for FP reconstruction are based on Gaussian measurements which cannot
      extend straightforwardly to long range, sub-diffraction imaging setup because of
      laser speckle noise corruption. In this work, a new FP reconstruction framework
      is proposed for macroscopic visible imaging. When compared with existing
      research, the reweighted amplitude flow algorithm is adopted for better signal
      modeling, and the Regularization by Denoising (RED) scheme is introduced to
      reduce the effects of speckle. Experiments demonstrate that the proposed method
      can obtain state-of-the-art recovered results on both visual and quantitative
      metrics without increasing computation cost, and it is flexible for real imaging
      applications.

PMID- 30231592
TI  - Zinc Supplementation Stimulates Red Blood Cell Formation in Rats.
AB  - In rats, mice, and humans, it is known that zinc deficiency may be related to
      anemia, and zinc supplementation influences hemoglobin production. Our previous
      studies indicate that in fish, zinc supplementation stimulates red blood cell
      (RBC) formation (erythropoiesis). However, it is not clear whether the mechanism
      of zinc-induced erythropoiesis stimulation in fish also occurs in rats. We
      induced anemia in rats using phenylhydrazine (PHZ) and injected either saline or
      ZnSO4 solution. We found that an appropriate amount of zinc stimulated
      erythropoiesis in the PHZ-induced anemic rats. The effects of ZnSO4 injection
      were dose-dependent. When the concentration of ZnSO4 was higher than 2.8 mg
      zinc/kg body weight, the RBC level of the anemic rats increased from 60 +/- 7% to
      88 +/- 10% that of the normal rats in two days. Rat bone marrow cells with or
      without ZnCl2 supplementation were cultured in suspension in vitro. In the cell
      culture when the zinc concentration was at 0.3 mM, a 1.6-fold proliferation of
      nascent immature reticulocytes (new RBCs) was observed after one day. In the rat
      blood, zinc was combined with serum transferrin to induce erythropoiesis. The
      stimulation of RBC formation by zinc appears to be common among different
      animals.

PMID- 30231596
TI  - Morphology of the epithelium in the alimentary tract of the larval lamprey,
      Petromyzon marinus L.
AB  - The alimentary tract of the ammocoete of the lamprey, Petromyzon marinus L., is
      divisible into three morphologically distinct regions: the oesophagus, the
      anterior intestine, and the posterior intestine. The epithelium of the oesophagus
      possesses mucous, ciliated, and columnar cells and appears to be specialized for
      movement of food particles. The epithelium of the anterior intestine possesses
      secretory cells with numerous zymogen granules, ciliated cells, and columnar
      absorptive cells. Although some absorption occurs in the anterior intestine, the
      main function of this region seems to be the release of digestive enzymes and the
      continued movement of food particles. The epithelium of the posterior intestine
      is entirely comprised of columnar absorptive cells, namely tall (light and dark)
      columnar and low columnar, and the primary function of this region is one of
      absorption. The epithelium of the hindgut resembles that of the archinephric duct
      (Youson and McMillan, '71). The morphology of the alimentary tract of ammocoetes
      suggests that some differentiation and renewal of cell types may occur in the
      epithelium of the three regions. Comparison of the alimentary tract of larval
      lamprey with that of other vertebrates indicates that the gut of the ammocoete
      represents a less specialized level of vertebrate development.

PMID- 30231597
TI  - Origin and evolution of insect wings and their relation to metamorphosis, as
      documented by the fossil record.
AB  - In contemporary entomology the morphological characters of insects are not always
      treated according to their phylogenetic rank. Fossil evidence often gives clues
      for different interpretations. All primitive Paleozoic pterygote nymphs are now
      known to have had articulated, freely movable wings reinforced by tubular veins.
      This suggests that the wings of early Pterygota were engaged in flapping
      movements, that the immobilized, fixed, veinless wing pads of Recent nymphs have
      resulted from a later adaptation affecting only juveniles, and that the paranotal
      theory of wing origin is not valid. The wings of Paleozoic nymphs were curved
      backwards in Paleoptera and were flexed backwards at will in Neoptera, in both to
      reduce resistance during forward movement. Therefore, the fixed oblique-backwards
      position of wing pads in all modern nymphs is secondary and is not homologous in
      Paleoptera and Neoptera. Primitive Paleozoic nymphs had articulated and movable
      prothoracic wings which became in some modern insects transformed into
      prothoracic lobes and shields. The nine pairs of abdominal gillplates of
      Paleozoic mayfly nymphs have a venation pattern, position, and development
      comparable to that in thoracic wings, to which they are serially homologous.
      Vestigial equivalents of wings and legs were present in the abdomen of all
      primitive Paleoptera and primitive Neoptera. The ontogenetic development of
      Paleozoic nymphs was confluent, with many nymphal and subimaginal instars, and
      the metamorphic instar was missing. The metamorphic instar originated by the
      merging together of several instars of old nymphs; it occurred in most orders
      only after the Paleozoic, separately and in parallel in all modern major lineages
      (at least twice in Paleoptera, in Ephemeroptera and Odonata; separately in
      hemipteroid, blattoid, orthopteroid, and plecopteroid lineages of exopterygote
      Neoptera; and once only in Endopterygota). Endopterygota evolved from
      ametabolous, not from hemimetabolous, exopterygote Neoptera. The full primitive
      wing venation consists of six symmetrical pairs of veins; in each pair, the first
      branch is always convex and the second always concave; therefore costa, subcosta,
      radius, media, cubitus, and anal are all primitively composed of two separate
      branches. Each pair arises from a single veinal base formed from a sclerotized
      blood sinus. In the most primitive wings the circulatory system was as follows:
      the costa did not encircle the wing, the axillary cord was missing, and the blood
      pulsed in and out of each of the six primary, convex-concave vein pair systems
      through the six basal blood sinuses. This type of circulation is found as an
      archaic feature in modern mayflies. Wing corrugation first appeared in preflight
      wings, and hence is considered primitive for early (paleopterous) Pterygota.
      Somewhat leveled corrugation of the central wing veins is primitive for Neoptera.
      Leveled corrugation in some modern Ephemeroptera, as well as accentuated
      corrugation in higher Neoptera, are both derived characters. The wing tracheation
      of Recent Ephemeroptera is not fully homologous to that of other insects and
      represents a more primitive, segmental stage of tracheal system. Morphology of an
      ancient articular region in Palaeodictyoptera shows that the primitive pterygote
      wing hinge in its simplest form was straight and composed of two separate but
      adjoining morphological units: the tergal, formed by the tegula and axillaries;
      and the alar, formed by six sclerotized blood sinuses, the basivenales. The
      tergal sclerites were derived from the tergum as follows: the lateral part of the
      tergum became incised into five lobes; the prealare, suralare, median lobe,
      postmedian lobe and posterior notal wing process. From the tips of these lobes,
      five slanted tergal sclerites separated along the deep paranotal sulcus: the
      tegula, first axillary, second axillary, median sclerite, and third axillary.
      Primitively, all pteralia were arranged in two parallel series on both sides of
      the hinge. In Paleoptera, the series stayed more or less straight; in Neoptera,
      the series became V-shaped. Pteralia in Paleoptera and Neoptera have been
      homologized on the basis of the fossil record. A differential diagnosis between
      Paleoptera and Neoptera is given. Fossil evidence indicates that the major steps
      in evolution, which led to the origin first of Pterygota, then of Neoptera and
      Endopterygota, were triggered by the origin and the diversification of flight
      apparatus. It is believed here that all above mentioned major events in pterygote
      evolution occurred first in the immature stages.

PMID- 30231594
TI  - Oxidative Stress-Protective and Anti-Melanogenic Effects of Loliolide and Ethanol
      Extract from Fresh Water Green Algae, Prasiola japonica.
AB  - Loliolide is a monoterpenoid hydroxylactone found in many algae, including fresh
      water green algae, Prasiola japonica. To date, loliolide and compounds in P.
      japonica have not been studied systematically with respect to skin pharmacology.
      In this study, we investigated oxidative stress-protective and anti-melanogenic
      effects of loliolide and P. japonica ethanol extract (Pj-EE), known to contain
      loliolide, in human keratinocyte (HaCaT) cells and mouse melanoma (B16F10) cells.
      Loliolide suppressed the transcription of genes encoding matrix
      metalloproteinases (MMPS), which were induced in HaCaT cells by hydrogen peroxide
      (H2O2) treatment. Loliolide and Pj-EE not only reduced the melanin secretion and
      content in B16F10 cells but also increased the expression of the antioxidant
      proteins nuclear factor (erythroid-derived 2)-like 2 (NRF2) and heme oxygenase-1
      (HO-1) in HaCaT cells subjected to H2O2 treatment. Furthermore, loliolide and Pj
      EE decreased expression of the anti-melanogenic protein microphthalmia-associated
      transcription factor (MITF) and tyrosinase in B16F10 cells subjected to alpha
      melanocyte-stimulating hormone (alpha-MSH) treatment. Our findings demonstrate
      that loliolide and Pj-EE have antioxidant and anti-melanogenic effects on skin.

PMID- 30231595
TI  - Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD
      Induced by Dietary Cholesterol.
AB  - While the impact of dietary cholesterol on the progression of atherosclerosis has
      probably been overestimated, increasing evidence suggests that dietary
      cholesterol might favor the transition from blunt steatosis to non-alcoholic
      steatohepatitis (NASH), especially in combination with high fat diets. It is
      poorly understood how cholesterol alone or in combination with other dietary
      lipid components contributes to the development of lipotoxicity. The current
      study demonstrated that liver damage caused by dietary cholesterol in mice was
      strongly enhanced by a high fat diet containing soybean oil-derived omega6-poly
      unsaturated fatty acids (omega6-PUFA), but not by a lard-based high fat diet
      containing mainly saturated fatty acids. In contrast to the lard-based diet the
      soybean oil-based diet augmented cholesterol accumulation in hepatocytes,
      presumably by impairing cholesterol-eliminating pathways. The soybean oil-based
      diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing
      oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This
      resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis,
      and caused a transition from steatosis to NASH, doubling the NASH activity score.
      Thus, the recommendation to reduce cholesterol intake, in particular in diets
      rich in omega6-PUFA, although not necessary to reduce the risk of
      atherosclerosis, might be sensible for patients suffering from non-alcoholic
      fatty liver disease.

PMID- 30231599
TI  - Structure of the integument in Paranthessius anemoniae claus, a copepod associate
      of the snakelocks anemone Anemonia sulcata (Pennant).
AB  - The integument of Paranthessius anemoniae has been studied with light and
      electron microscopy. A cuticle with clearly defined epicuticular, exocuticular
      and endocuticular regions overlies a cellular hypodermal layer. The distribution
      of carbohydrate, lipid and protein components of the cuticle were demonstrated
      histochemically. Parabolic striations in oblique sections of cuticle suggest that
      its molecular architecture fits a "twisted sheet" theory proposed for other
      species. Arthrodial membranes at body and limb joints have a homogeneous
      structure, lacking exocuticle and endocuticle. Subcuticular glands appear to
      secrete substances thought to be responsible for the immunity which Paranthessius
      seems to have to the nematocysts of its host. Small hairs, situated in cuticular
      cups which occur over the dorsal body surface are considered to function as
      rheoreceptors.

PMID- 30231598
TI  - Observations on the brain of the coelacanth Latimeria chalumnae: External anatomy
      and quantitative analysis.
AB  - New data on the brain of Latimeria indicate that previous estimates of the brain
      weight were too high by a factor of two. Our data suggest a brain weight of 1.1
      1.5 grams for a specimen with a body weight of 30 kilograms. Quantitative data on
      major divisions of the brain are presented for the first time, and the relative
      size of the major brain divisions is similar to that of sturgeons and generalized
      sharks (such as hexanchids and squalids). Examination of brain component weight
      (s): body weight plots in a sample of non-teleost actinopterygian fishes
      indicates that all major divisions of the brain, except the telencephalon, are
      larger than in Latimeria. Brain component sizes in Latimeria are more similar to
      those extrapolated for amphibian brains than to those for actinopterygians.
      However, the cerebellum of Latimeria is considerably larger than that of
      amphibians.

PMID- 30231600
TI  - Studies on the mid-gut of the desert locust Schistocerca gregaria. II.
      Ultrastructure of the muscle coat and its innervation.
AB  - The fine structure of the mid-gut musculature of the desert locust, Schistocerca
      gregaria is described and compared with that of the visceral muscles of other
      species. The gross morphology and fine structure of the nervous system which
      supplies the mid-gut muscle fibres is described.

PMID- 30231601
TI  - Sense organs on the antennae of two species of collembola (insecta).
AB  - The antennae of Folsomia candida and Hypogastrura copiosa are provided with
      tactile hairs on all four segments and, in addition, with chemoreceptors on
      segments three and four. The cuticle of the thin-walled chemo-receptors of
      Folsomia, as in most other insects, is penetrated by many small pores uniformly
      distributed over the surface. In contrast, the cuticle of the thin-walled
      chemoreceptors of Hypogastrura is unusual in that a band of cuticle without
      perforations spirals around, or partly around, the hair. The cuticle between the
      spirals is very thin, and has extremely small openings in it. The tip of the
      antenna of Folsomia is thin, permeable to dyes in aqueous solution and apparently
      glandular. The antennal tip of Hypogastrura is definitely glandular.

PMID- 30231602
TI  - The anatomy of the forelimb in the anteater (Tamandua) and its functional
      implications.
AB  - The forelimbs of anteaters play a major role in obtainment of food, defense, and
      locomotion. The greatly enlarged claws on the manus are used for ripping open
      insect nests and insect-infested wood; the claws also serve as the animals' only
      defensive weapons, since they lack teeth. Specialization of the claws for these
      functions has also had a substantial effect on the ways in which the forelimb is
      used for posture and locomotion. Modifications of the forelimb in the anteater
      Tamandua include the following. Attachments of the medial head of triceps are
      rearranged so as to greatly increase capability for powerful flexion of the
      claws. Ability to flex the elbow and to retract the humerus is also augmented;
      these movements would assist digital flexion in applying traction with the claws
      to material being torn away during food procurement. This traction can be
      supplemented by a variety of powerful side-to-side and/or twisting movements of
      the hand, brought about primarily by axial rotation of the upper arm and forearm.
      The digital joints are reinforced to resist the deviational and torsional loading
      to which the digits would be subjected during such movements. The morphological
      modifications of the forelimb in Tamandua are discussed in terms of how they
      affect the mechanical capabilities of the limb, what functions the limb is best
      designed to perform, how they may relate to what little is known about the
      specialized behavior of this animal, and what behavioral predictions may be made
      based on mechanical design.

PMID- 30231603
TI  - Studies on the annual reproductive cycle of the female cobra, Naja naja. IV.
      OVARIAN HISTOLOGY.
AB  - Morphological changes of the ovary of the Chinese cobra, Naja naja, throughout
      the annual reproductive cycle are described. A single clutch of between 6 and 22
      eggs is produced in late June. From July to the following April the ovary remains
      quiescent and contains small previtellogenic, hydration stage follicles. The
      growth of an ovarian follicle from a primary oocyte to maturation and ovulation
      is estimated to take three years. The histology of the germinal epithelium and
      the follicular granulosa shows seasonal changes correlated with the growth of the
      oocyte. During the quiescent period, the germinal epithelium lacks mitotic
      activity, but during April, when yolk deposition and rapid growth of the
      preovulatory follicles take place, the germinal epithelium shows intense mitotic
      activity. The growth of the smallest hydration stage follicles, and the
      occurrence of cytoplasmic bridges between the pyriform cells of the granulosa and
      the developing oocyte, also appear to increase during this period. The possible
      function of the pyriform cell is discussed and the literature on the origin and
      fate of these cells in the squamate ovary is reviewed. Postovulatory follicles
      (corpora lutea) and two types of atresia are described and compared with what is
      known of these structures in other reptiles.

PMID- 30231604
TI  - Reinforced tracheoles in three firefly lanterns: Further reflections on
      specialized tracheoles.
AB  - The structures of the lantern tracheoles of three genera of flashing fireflies
      are compared. All three genera have stiff, reinforced tracheoles which resist
      folding or collapsing under conditions which flatten more typical tracheoles.
      This common specialization supports the hypothesis that the tracheoles play a
      major role in flash control in these fireflies, especially as the morphological
      basis of the stiffening is different in the three genera. Study of the tracheoles
      of other tissues reveals that there is great variety in structure and flexibility
      of these vessels from tissue to tissue and organism to organism, suggesting that
      tracheolar specialization may be a general phenomenon, with the fine structure of
      these air tubes being tailored to the particular demands and conditions of the
      tissues in which they are found.

PMID- 30231606
TI  - Transglutaminase 2 Promotes Autophagy by LC3 Induction Through p53 Depletion in
      Cancer Cell.
AB  - Transglutaminase 2 (TGase 2) plays a key role in p53 regulation, depleting p53
      tumor suppressor through autophagy in renal cell carcinoma. We found that
      microtubule-associated protein 1A/1B-light chain 3 (LC3), a hallmark of
      autophagy, were tightly associated with the level of TGase 2 in cancer cells.
      TGase 2 overexpression increased LC3 levels, and TGase 2 knockdown decreased LC3
      levels in cancer cells. Transcript abundance of LC3 was inversely correlated with
      level of wild type p53. TGase 2 knockdown using siRNA, or TGase 2 inhibition
      using GK921 significantly reduced autophagy through reduction of LC3
      transcription, which was followed by restoration of p53 levels in cancer cells.
      TGase 2 overexpression promoted the autophagy process by LC3 induction, which was
      correlated with p53 depletion in cancer cells. Rapamycin-resistant cancer cells
      also showed higher expression of LC3 compared to the rapamycin-sensitive cancer
      cells, which was tightly correlated with TGase 2 levels. TGase 2 knockdown or
      TGase 2 inhibition sensitized rapamycin-resistant cancer cells to drug treatment.
      In summary, TGase 2 induces drug resistance by potentiating autophagy through LC3
      induction via p53 regulation in cancer.

PMID- 30231605
TI  - Development of a Label-Free LC-MS/MS-Based Glucosylceramide Synthase Assay and
      Its Application to Inhibitors Screening for Ceramide-Related Diseases.
AB  - Ceramide metabolism is known to be an essential etiology for various diseases,
      such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is
      a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main
      ceramide metabolism pathway in mammalian cells. In this article, we developed a
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS
      activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The
      reaction products, C8-GlcCer for GCS, could be separated on a C18 column by
      reverse-phase high-performance liquid chromatography (HPLC). Quantification was
      conducted using the multiple reaction monitoring (MRM) mode to monitor the
      precursor-to-product ion transitions of m/z 588.6 -> 264.4 for C8-GlcCer at
      positive ionization mode. The calibration curve was established over the range of
      0.625-160 ng/mL, and the correlation coefficient was larger than 0.999. This
      method was successfully applied to detect GCS in the human hepatocellular
      carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells.
      We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2
      decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved
      that this method could be successfully applied to GCS inhibitor screening of
      preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic
      dermatitis and Gaucher disease.

PMID- 30231607
TI  - Neolignan Constituents with Potential Beneficial Effects in Prevention of Type 2
      Diabetes from Viburnum fordiae Hance Fruits.
AB  - Nine new neolignan glycosides (1-9), viburfordosides A-I, two new neolignans,
      fordianes A and B (10, 11), and seven known analogues (12-18) have been isolated
      and identified from the fruits of Viburnum fordiae Hance. The structures and
      absolute configurations of undescribed neolignan constituents were identified by
      chemical methods and spectroscopic analyses. The alpha-glucosidase inhibitory,
      ABTS*+ and DPPH* scavenging, and anti-inflammatory activities of these secondary
      metabolites were evaluated. Some of them exhibited significant potency in
      inhibiting alpha-glucosidase and scavenging free radicals. Among the 14
      metabolites that were found to have the capacity to inhibit NO production in LPS
      stimulated RAW264.7 macrophage cells, compounds 2, 4, 6, 10, 11, 14, 17, and 18
      were potent with IC50 values of 10.88-41.10 MUM. These results support that V.
      fordiae fruits possessing the neolignan compounds may serve as both a functional
      food and a medicinal resource to prevent and treat type 2 diabetes (T2D).

PMID- 30231608
TI  - One-Pot Dual Labeling of IgG 1 and Preparation of C-to-C Fusion Proteins Through
      a Combination of Sortase A and Butelase 1.
AB  - Site-specific chemical modification of proteins can assist in the study of their
      function. Furthermore, these methods are essential to develop biologicals for
      diagnostic and therapeutic use. Standard protein engineering protocols and
      recombinant expression enable the production of proteins with short peptide tags
      recognized by enzymes capable of site-specific modification. We report here the
      application of two enzymes of orthogonal specificity, sortase A and butelase 1,
      to prepare non-natural C-to-C fusion proteins. Using these enzymes, we further
      demonstrate site-selective installation of different chemical moieties at two
      sites in a full-size antibody molecule.

PMID- 30231609
TI  - Facile Electrodeposition of Ni-Cu-P Dendrite Nanotube Films with Enhanced
      Hydrogen Evolution Reaction Activity and Durability.
AB  - Hydrogen can be the potential substitute energy carrier for fuel while
      electrolysis water with hydrogen evolution reaction (HER) is an efficient way to
      produce hydrogen. Highly active and robust electrocatalysts composed by earth
      abundant elements are required. Herein, nickel-copper-phosphorus (Ni-Cu-P)
      electrocatalysts are designed and synthesized by a facile one-step
      electrodeposition method. A unique pine-needle-like dendrite nanotube morphology
      of Ni-Cu-P electrocatalyst can be synthesized when copper content changed and
      impressive HER activity obtained in alkaline and acidic media. Briefly, the
      overpotential reaches 120 mV in 1 M KOH and 150 mV in 0.5 M H2SO4 at the current
      density of 10 mA cm-2, with the corresponding Tafel slope reaching 69 mV dec-1.
      The results are close to that of commercial Pt/C catalysts (37 mV in 1 M KOH).
      Furthermore, the density functional theory calculations also demonstrate that P
      incorporated Ni-Cu, Cu-incorporated Ni-P, and Ni-incorporated Cu-P have the
      optimized hydrogen adsorption free energy (Delta GH*) of -0.066, -0.157, and 
      0.003 eV, respectively, which are more suitable than those of Ni-Cu, Ni-P, and Cu
      P, respectively. The Ni-incorporated Cu-P even has a much smaller Delta GH* of 
      0.003 than that of Pt (~-0.09 eV). We believe that our study will provide a new
      strategy to design non-noble metal alloy materials for practical applications in
      catalysis and energy fields.

PMID- 30231610
TI  - Palladium-Catalyzed Selective Five-Fold Cascade Arylation of the 12-Vertex
      Monocarborane Anion by B-H Activation.
AB  - A series of cage penta-arylated carboranes have been synthesized by palladium
      catalyzed intermolecular coupling of the C-carboxylic acid of the monocarba-
      closo-dodecaborate anion [CB11H12]- with iodoarenes by direct cage B-H bond
      functionalization. These transformations set a record in terms of one-pot
      directing group-mediated activation of inert bonds in a single molecule. The
      methodology is characterized by high yields, good functional group tolerance, and
      complete cage regioselectivity. The directing group COOH can be easily removed
      during or after the intermolecular coupling reaction. The mechanistic pathways
      were probed using density functional theory calculations. A Pd(II)-Pd(IV)-Pd(II)
      catalytic cycle is proposed, in which initial coupling is followed by preferred B
      H activation of the adjacent boron vertex, and continuation of this selectivity
      results in a continuous walking process of the palladium center. The methodology
      opens a new avenue toward building blocks with 5-fold symmetry.

PMID- 30231611
TI  - Glucose Glycation of alpha-Lactalbumin and beta-Lactoglobulin in Glycerol
      Solutions.
AB  - The glucose glycation of alpha-lactalbumin and beta-lactoglobulin at 50  degrees
      C in a glycerol-based liquid system was investigated to evaluate the effect of
      water activity on glycation and site-specificity in a glycerol matrix. Glycation
      extent during the reaction was determined using the o-phthalaldehyde (OPA) method
      as well as ultraperformance liquid chromatography combined with electro-spray
      ionization mass spectrum (UPLC-ESI-MS) analysis. Glycation sites were identified
      by data-independent acquisition LC-MS (LC-MSE). The surface potential achieved by
      PyMOL and the tertiary structure determined by circular dichroism (CD) were used
      to assist the analysis of the glycation site-specificity in the glycerol matrix.
      The water activity of glycerol solutions was negatively correlated to the
      glycerol concentration. Results showed that the initial glycation rate in
      glycerol matrix was fitted to a linear equation in the first 48 h. Glycation
      accelerated with the increase of glycerol concentration, namely, the decrease of
      water activity, regardless of the native structure of the protein. The glycation
      sites were identical at a similar DSP although achieved at different water
      activities, with 4 and 7 sites detected in alpha-lactalbumin and beta
      lactoglobulin, respectively. However, compared with the glycation sites in a
      water-based matrix, the site-specificity of glycation was affected by the
      glycerol matrix, depending on the native structure of the proteins. Glycation was
      prone to occur at the reactive sites distributed on the surface of the proteins,
      particularly in the region with positive potential.

PMID- 30231612
TI  - Branching Ratio Measurements of the Predissociation of 12C16O by Time-Slice
      Velocity-Map Ion Imaging in the Energy Region from 106 250 to 107 800 cm-1.
AB  - Photodissociation of CO is a fundamental chemical mechanism for mass-independent
      oxygen isotope fractionation in the early Solar System. Branching ratios of
      photodissociation channels for individual bands quantitatively yield the trapping
      efficiencies of atomic oxygen resulting into oxides. We measured the branching
      ratios for the spin-forbidden and spin-allowed photodissociation channels of
      12C16O in the vacuum ultraviolet (VUV) photon energy region from 106 250 to 107
      800 cm-1 using the VUV laser time-slice velocity-map imaging photoion technique.
      The excitations to four 1Pi bands and three 1Sigma+ bands of 12C16O were
      identified and investigated. The branching ratios for the product channels C(3P)
      + O(3P), C(1D) + O(3P), and C(3P) + O(1D) of these predissociative states
      strongly depend on the electronic and vibrational states of CO being excited. By
      plotting the branching ratio of the spin-forbidden dissociation channels versus
      the excitation energy from 102 500 to 110 500 cm-1 that has been measured so far,
      the global pattern of the 1Pi-3Pi interaction that plays a key role in the
      predissociation of CO is revealed and discussed.

PMID- 30231613
TI  - Rapid, Wet Chemical Fabrication of Radial Junction Electroluminescent Wires.
AB  - A wet chemical process involving two electrodeposition steps followed by a
      solution casting step, the "EESC" process, is described for the fabrication of
      electroluminescent, radial junction wires. EESC is demonstrated by assembling
      three well-studied nanocrystalline (or amorphous) materials: Au, CdSe, and
      poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS). The tri
      layered device architecture produced by EESC minimizes the influence of an
      electrically resistive CdSe emitter layer by using a highly conductive gold
      nanowire that serves as both a current collector and a negative electrode. Hole
      injection, at a high barrier CdSe-PEDOT:PSS interface (phih ~ 1.1 V), is
      facilitated by a contact area that is 1.9-4.7-fold larger than the complimentary
      gold-CdSe electron-injecting contact (phie ~ 0.6 V), contributing to low-voltage
      thresholds (1.4-1.7 V) for electroluminescence (EL) emission. Au@CdSe@PEDOT:PSS
      wire EL emitters are 25 MUm in length, amongst the longest so far demonstrated to
      our knowledge, but the EESC process is scalable to nanowires of any length,
      limited only by the length of the central gold nanowire that serves as a template
      for the fabrication process. Radial carrier transport within these multishell
      wires conforms to the back-to-back diode model.

PMID- 30231614
TI  - Probing the Lowest-Lying Electronic States of Acrylic Acid by Experimental and
      Theoretical Methods.
AB  - We report a combined experimental and theoretical study of the electronic state
      spectroscopy of acrylic acid (C3H4O2) in the gas phase, by high-resolution vacuum
      ultraviolet (VUV) photoabsorption measurements in the 4.0-10.8 eV energy range,
      together with ab initio calculations (vertical energies and oscillator
      strengths), which were used in the assignment of the valence transitions. We also
      discuss the Rydberg transitions for this molecular target, obtained using the
      experimental ionization energies available in the literature. The experimental
      spectrum presented in this paper represents the highest resolution data yet
      reported for acrylic acid and reveals new features not previously reported in the
      literature. The dominant transitions have been assigned to (pi*(4a") <- pi(3a"))
      and (pi*(4a") <- pi(2a")), the latter exhibiting excitation of the nu5'( a') C =
      O stretching mode with mean energy of 0.155 eV. The measured absolute
      photoabsorption cross sections have been used to calculate the photolysis
      lifetime of acrylic acid in the upper stratosphere (20-50 km).

PMID- 30231616
TI  - Spotlights: Volume 9, Issue 18.

PMID- 30231615
TI  - Influence of Branching on the Conformational Space: Case Study of Tri- sec-butyl
      Phosphate Using Matrix Isolation Infrared Spectroscopy and DFT Computations.
AB  - The conformational analysis of long chain phosphates poses a serious challenge
      due to the presence of rotationally flexible multiple alkyl groups. Tri- sec
      butyl phosphate (TsBP) is an interesting example, in which branching can be
      expected to influence the conformational landscape. To solve the conformational
      problem of TsBP systematically, the conformations of model dimethyl- sec-butyl
      phosphate (DMsBP), a molecule possessing a single secondary butyl strand, were
      analyzed. On the basis of the analysis of the energy profile of DMsBP, a few
      conformational bunches were eliminated. The presence of branched methyl group
      appears to completely influence the conformational space of TsBP and as a result,
      the number of conformations is drastically reduced in comparison to its
      structural isomer, tri- n-butyl phosphate (TBP). B3LYP level of theory in
      association with 6-311++G(d,p) basis set was used for computing all the conformer
      geometries. Experimentally, the conformations of TsBP were studied using infrared
      spectroscopy by trapping the molecule in N2 and Ar matrixes at low temperatures,
      which were correlated well with the computational results.

PMID- 30231618
TI  - SYNTAX Score and Severity of Atherosclerosis.

PMID- 30231619
TI  - Cerebrovascular Events in Stenting for Carotid Artery Stenosis.

PMID- 30231617
TI  - Exploring the anomalous cytotoxicity of commercially-available poly(N-isopropyl
      acrylamide) substrates.
AB  - Poly(N-isopropyl acrylamide) (pNIPAM) is a stimulus-responsive polymer that has
      been of great interest to the bioengineering community. When the temperature is
      lowered below its lower critical solution temperature (~32  degrees C), pNIPAM
      rapidly hydrates, and adherent cells detach as intact cell sheets. This cell
      releasing behavior in a physiologically relevant temperature range has led to
      NIPAM's use for engineered tissues and other devices. In a previous study,
      however, the authors found that although most techniques used to polymerize NIPAM
      yield biocompatible films, some formulations from commercially-available NIPAM
      (cpNIPAM) can be cytotoxic. In this work, the authors investigate the reasons
      underlying this anomaly. The authors evaluated the response of a variety of cell
      types (e.g., bovine aortic endothelial cells, BAECs; monkey kidney epithelial
      cells, Vero cells; and mouse embryonic fibroblasts, 3T3s) after culture on
      substrates spin-coated with sol-gel (spNIPAM) and commercially-prepared
      (cpNIPAM). The relative biocompatibility of each cell type was evaluated using
      observations of its cell morphology and function (e.g., XTT and Live/Dead assays)
      after 48 and 96 h in culture. In addition, the substrates themselves were
      analyzed using NMR, goniometry, and XPS. The authors find that all the cell types
      were compromised by 96 h in culture with cpNIPAM, although the manner in which
      the cells are compromised differs; in particular, while Vero and 3T3 cells appear
      to be undergoing cytotoxic death, BAECs undergo apoptic death. The authors
      believe that this result is due to a combination of factors, including the
      presence of short chain oligomers of NIPAM in the commercially-available
      preparation. This work will provide valuable insights into the cytotoxicity of
      commercially-prepared polymer substrates for this type of bioengineering work and
      therefore into the applicability of cells grown on such surfaces for human
      subjects.

PMID- 30231620
TI  - Radiation treatment monitoring with DCE-US in CWR22 prostate tumor xenografts.
AB  - Background Longitudinal monitoring of potential radiotherapy treatment effects
      can be determined by dynamic contrast-enhanced ultrasound (DCE-US). Purpose To
      assess functional parameters by means of DCE-US in a murine subcutaneous model of
      human prostate cancer, and their relationship to dose deposition and time-frame
      after treatment. A special focus has been placed to evaluate the vascular
      heterogeneity of the tumor and on the most suitable data analysis approach that
      reflects this heterogeneity. Material and Methods In vivo DCE-US was acquired 24
      h and 48 h after radiation treatment with a single dose of 7.5 Gy and 10 Gy,
      respectively. Tumor vasculature was characterized pixelwise using the Brix
      pharmacokinetic analysis of the time-intensity curves. Results Longitudinal
      changes were detected ( P < 0.001) at 24 h and 48 h after treatment. At 48 h, the
      eliminating rate constant of the contrast agent from the plasma, kel, was
      correlated ( P <= 0.05) positively with microvessel density (MVD; rtau = 0.7) and
      negatively with necrosis (rtau = -0.6) for the treated group. Furthermore, Akep,
      a parameter related to transcapillary transport properties, was also correlated
      to MVD (rtau = 0.6, P <= 0.05). Conclusion DCE-US has been shown to detect
      vascular changes at a very early stage after radiotherapy, which is a great
      advantage since DCE-US is non-invasive, available at most hospitals, and is low
      in cost compared to other techniques used in clinical practice.

PMID- 30231621
TI  - Advantages and Pitfalls of the Glycated Hemoglobin A1c Measurement in Acute
      Coronary Syndrome: Start Simple, Evolve to More Sophisticated.

PMID- 30231622
TI  - Status of Diabetes Mellitus or HbA1c Levels for Burden of Coronary Artery
      Disease.

PMID- 30231623
TI  - Economics of dementia: A review of methods.
AB  - Given the expected increase in the number of people with dementia in the coming
      years, it is anticipated that the resources necessary to support those with
      dementia will significantly increase. There will therefore likely be increased
      emphasis on how best to use limited resources across a number of domains
      including prevention, diagnosis, treatment and supporting informal caregivers.
      There has been increasing use of economic methods in dementia in the past number
      of years, in particular, cost-of-illness analysis and economic evaluation. This
      paper reviews the aforementioned methods and identities a number of
      methodological issues that require development. Addressing these methodological
      issues will enhance the quality of economic analysis in dementia and provide some
      useful insights about the best use of limited resources for dementia.

PMID- 30231624
TI  - Trends in the Incidence and In-Hospital Outcomes of Patients With Atrial
      Fibrillation Complicated by Non-ST-Segment Elevation Myocardial Infarction.
AB  - Atrial fibrillation (AF) can present with non-ST-segment elevation myocardial
      infarction (NSTEMI). The incidence, characteristics, outcomes, and treatment of
      this subgroup of patients with AF remains poorly studied. Using data from the
      National Inpatient Sample database, we (1) compared baseline characteristics of
      patients with AF with/without NSTEMI, (2) evaluated their outcomes and associated
      trends over the study period (2004-2013), and (3) evaluated revascularization (by
      percutaneous coronary intervention or coronary artery bypass graft [CABG]) and
      the impact on patient outcomes. Of the 3 923 436 patients admitted with a primary
      diagnosis of AF, 47 785 (1.2%) had a secondary diagnosis of NSTEMI. In this
      subgroup with AF and NSTEMI, there was a significant trend toward a decrease in
      mortality ( P = .002), stroke ( P < .001), and gastrointestinal bleeding ( P <
      .001) during the study period. Compared to unrevascularized patients,
      revascularized patients were more likely to be younger (72.2 +/- 10.2 vs 77.0 +/-
      11.8 years old, P < .001), male (57.8 vs 42.7%, P < .001), and had a much higher
      incidence of coronary risk factors. Revascularization was associated with
      increased survival in multivariable analysis (odds ratio: 0.562, 95% confidence
      interval: 0.334-0.946, P = .03). In conclusion, among patients admitted with AF,
      1.2% were diagnosed with NSTEMI. A minority of patients with AF and NSTEMI
      underwent revascularization and had better in-hospital outcomes.

PMID- 30231626
TI  - Benefit-risk assessment of erenumab and current migraine prophylactic treatments
      using the likelihood of being helped or harmed.
AB  - Objective This study evaluated the benefit-risk profile of erenumab relative to
      other therapies approved for migraine prophylaxis and available in the majority
      of European countries. Methods Trials were identified via a published systematic
      literature review updated to December 2017 using MEDLINE. Erenumab's pivotal
      trials study reports were also included (NCT02066415, NCT02456740). From these
      sources, >= 50% responder rates and discontinuations due to adverse events were
      extracted to generate numbers needed to treat and harm and likelihood of being
      helped or harmed, a quantitative benefit-risk measure. Results Eleven articles
      (nine randomized clinical trials) met the inclusion/exclusion criteria. Low
      numbers needed to treat (range: 4-13) were observed for most treatments, while
      numbers needed to harm showed substantial differences (erenumab's higher numbers
      needed to harm indicating better tolerability). In chronic and episodic migraine,
      likelihoods of being helped or harmed for erenumab 70 mg were 143 and 167, and 42
      and 167 for erenumab 140 mg. Likelihoods of being helped or harmed in chronic
      migraine were 2 and 3 for topiramate (two studies) and 4 for onabotulinumtoxinA.
      In episodic migraine, likelihoods of being helped or harmed were 2 for topiramate
      and 2 for propranolol. Conclusions While all prophylactic treatments were more
      likely to help than harm (likelihood of being helped or harmed > 1), erenumab
      showed a likelihood of being helped or harmed of high magnitude, supporting its
      favorable benefit-risk profile across the entire migraine frequency spectrum, in
      contrast with other prophylactic treatments.

PMID- 30231627
TI  - More About the Effect of Dynamic Potassium Change in STEMI.

PMID- 30231628
TI  - Leaky brain in neurological and psychiatric disorders: Drivers and consequences.
AB  - BACKGROUND: The blood-brain barrier acts as a highly regulated interface; its
      dysfunction may exacerbate, and perhaps initiate, neurological and
      neuropsychiatric disorders. METHODS: In this narrative review, focussing on
      redox, inflammatory and mitochondrial pathways and their effects on the blood
      brain barrier, a model is proposed detailing mechanisms which might explain how
      increases in blood-brain barrier permeability occur and can be maintained with
      increasing inflammatory and oxidative and nitrosative stress being the initial
      drivers. RESULTS: Peripheral inflammation, which is causatively implicated in the
      pathogenesis of major psychiatric disorders, is associated with elevated
      peripheral pro-inflammatory cytokines, which in turn cause increased blood-brain
      barrier permeability. Reactive oxygen species, such as superoxide radicals and
      hydrogen peroxide, and reactive nitrogen species, such as nitric oxide and
      peroxynitrite, play essential roles in normal brain capillary endothelial cell
      functioning; however, chronically elevated oxidative and nitrosative stress can
      lead to mitochondrial dysfunction and damage to the blood-brain barrier.
      Activated microglia, redox control of which is mediated by nitric oxide synthases
      and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, secrete
      neurotoxic molecules such as reactive oxygen species, nitric oxide,
      prostaglandin, cyclooxygenase-2, quinolinic acid, several chemokines (including
      monocyte chemoattractant protein-1 [MCP-1], C-X-C motif chemokine ligand 1 [CXCL
      1] and macrophage inflammatory protein 1alpha [MIP-1alpha]) and the pro
      inflammatory cytokines interleukin-6, tumour necrosis factor-alpha and
      interleukin-1beta, which can exert a detrimental effect on blood-brain barrier
      integrity and function. Similarly, reactive astrocytes produce neurotoxic
      molecules such as prostaglandin E2 and pro-inflammatory cytokines, which can
      cause a 'leaky brain'. CONCLUSION: Chronic inflammatory and oxidative and
      nitrosative stress is associated with the development of a 'leaky gut'. The
      following evidence-based approaches, which address the leaky gut and blood-brain
      barrier dysfunction, are suggested as potential therapeutic interventions for
      neurological and neuropsychiatric disorders: melatonin, statins, probiotics
      containing Bifidobacteria and Lactobacilli, N-acetylcysteine, and prebiotics
      containing fructo-oligosaccharides and galacto-oligosaccharides.

PMID- 30231629
TI  - Improving the impact of treatments and services.

PMID- 30231630
TI  - Phenomenal insights: Is the idea of defining a delusion overvalued?

PMID- 30231631
TI  - ?

PMID- 30231633
TI  - [Laser surgery on varicose veins].
AB  - INTRODUCTION: With the development of medicine, technical inventions have been
      intoduced into the therapy of varicose veins, such as ultrasound examination and
      laser treatment. PATIENTS AND METHODS: Over 11 years 1729 laser surgery were
      performed on varicose veins. Junctions of saphenous veins, saphenous stems and
      perforator veins were treated with lasers, but reticular and spider veins were
      treated with other methods. The most important elements of laser surgery are the
      introduction of the laser fibre into the lumen of the vein and delivering the
      laser energy. All of this is performed without incisions under ultrasound
      guidance. Laser crossectomy is an innovation in our technique. This procedure is
      performed under a combination of local and intravenous anaesthesia. RESULTS:
      After 1 year 58% of operated legs (998) were checked (mean 3.3 years) and
      recurrent varicosity was found in 114 legs (11.4%). Recurrences were found mainly
      in those cases which would have been excluded from other studies, but in everyday
      practice they occur in a high percentage, such as being overweight, after
      delivery and previously operated cases. In selected cases, the recurrence rate is
      only 6.0%. Complications after laser surgery are less frequent than following
      classic varicose vein surgery. CONCLUSIONS: According to international guidelines
      and this study, endovascular interventions can be recommended instead of classic
      varicose vein surgery because they are less demanding, and cause fewer
      complications. Using laser crossectomy, the number of early recurrences
      decreases. All stem varicosities are suitable for laser surgery.

PMID- 30231636
TI  - ?

PMID- 30231634
TI  - [Treatment of adult intrapulmonary sequestration with video-assisted
      thoracoscopic lobectomy].
AB  - INTRODUCTION: Surgical removal is the gold standard method for the treatment of
      pulmonary sequestration (PS); nowadays, video-assisted thoracoscopic lobectomy
      (VATS) is more frequently applied in the surgical treatment of malignant
      pulmonary tumours and appears to be suitable also in case of benign pulmonary
      diseases. We are the first in Hungary, who report three, radiologically
      identified intralobar PS treated with VATS. METHOD: Surgeries were performed in
      general anaesthesia with double-lumen separated ventilation in lateral decubitus
      position through two ports (1.5 cm camera port and 5-6 cm axillary working port,
      protected by a plastic ring). Results and cases: Two of the patients presented
      with the symptoms of haemoptysis and pneumonia, and the third patient after
      radiological screening (one 37 years old woman and 2 men, 39 and 46 years old).
      The nutritive artery was identified on the CT scans in all cases. We removed the
      right lower lobe in two cases and the left lower lobe in one case without major
      complications. CONCLUSION: We recommend the video-thoracoscopic lobectomy for the
      treatment of PS as a suitable treatment option.

PMID- 30231625
TI  - Sensory Processing Phenotypes in Fragile X Syndrome.
AB  - Fragile X syndrome (FXS) is a neurodevelopmental disorder that causes
      intellectual disability. It is a leading known genetic cause of autism. In
      addition to cognitive, social, and communication deficits, humans with FXS
      demonstrate abnormal sensory processing including sensory hypersensitivity.
      Sensory hypersensitivity commonly manifests as auditory, tactile, or visual
      defensiveness or avoidance. Clinical, behavioral, and electrophysiological
      studies consistently show auditory hypersensitivity, impaired habituation to
      repeated sounds, and reduced auditory attention in humans with FXS. Children with
      FXS also exhibit significant visuospatial impairments. Studies in infants and
      toddlers with FXS have documented impairments in processing texture-defined
      motion stimuli, temporal flicker, perceiving ordinal numerical sequence, and the
      ability to maintain the identity of dynamic object information during occlusion.
      Consistent with the observations in humans with FXS, fragile X mental retardation
      1 ( Fmr1) gene knockout (KO) rodent models of FXS also show seizures, abnormal
      visual-evoked responses, auditory hypersensitivity, and abnormal processing at
      multiple levels of the auditory system, including altered acoustic startle
      responses. Among other sensory symptoms, individuals with FXS exhibit tactile
      defensiveness. Fmr1 KO mice also show impaired encoding of tactile stimulation
      frequency and larger size of receptive fields in the somatosensory cortex. Since
      sensory deficits are relatively more tractable from circuit mechanisms and
      developmental perspectives than more complex social behaviors, the focus of this
      review is on clinical, functional, and structural studies that outline the
      auditory, visual, and somatosensory processing deficits in FXS. The similarities
      in sensory phenotypes between humans with FXS and animal models suggest a likely
      conservation of basic sensory processing circuits across species and may provide
      a translational platform to not just develop biomarkers but also to understand
      underlying mechanisms. We argue that preclinical studies in animal models of FXS
      can facilitate the ongoing search for new therapeutic approaches in FXS by
      understanding mechanisms of basic sensory processing circuits and behaviors that
      are conserved across species.

PMID- 30231635
TI  - [Computer-assisted decision-making in cardiac surgery: from 3D preoperative
      planning to computational fluid dynamics in the design of surgical procedures].
AB  - INTRODUCTION: Although surgical specialties utilize static models for
      preoperative planning, the evolution of dynamic planning methods and computer
      simulations created the opportunity for the introduction of dynamic parameters in
      cardiac surgery. Our aim was to apply 3D models in cardiac surgical practice,
      predicting fluid dynamic results, ventricular shape, volume and function before
      the operation. METHODS: Using a script developed by us, the raw DICOM files were
      imported, the dilated left ventricle was modeled and fluid dynamic parameters
      were simulated, such as flow kinematic and profile analysis, turbulence
      calculation and myocardial response to shear stress. Then step-by-step simulation
      of the surgical ventricle restoration procedure was accomplished and the
      calculated variables were imbedded in silico model. The length of resection lines
      was modified based on the previous computer simulation and applied during the
      operation, if feasible. RESULTS: The sphericity and conicity indexes were
      improved significantly in postoperative period (0.42 vs. 0.67 and 0.36 vs. 0.72,
      p < 0.05). The occurred shear stress at endocardium decreased 83% due to the
      normalization of flow kinematic pattern of the ventricle in postoperative period
      (132.21 +/- 29.5 dyne/cm2 vs. 22.92 +/- 10.3 p < 0.05 dyne/?cm2). The
      postoperative turbulent flow pattern significantly decreased, according to our
      computational method (2712 vs. 1823, p < 0.0001). CONCLUSION: With our method,
      the standardization of the surgical ventricle reconstruction was achievable and
      the surgical steps were predictable. Therefore, a new decision making support
      system was established in cardiac surgery for high risk patients. A personalized
      surgical technique was offered to our patients, improving their life expectancy
      and quality of life.

PMID- 30231638
TI  - War, law and humanity, the campaign to control warfare, 1853-1914.

PMID- 30231637
TI  - Effects of Emergency Department Physical Design Elements on Security, Wayfinding,
      Visibility, Privacy, and Efficiency and Its Implications on Staff Satisfaction
      and Performance.
AB  - OBJECTIVE: The purpose of this study was to identify the role of emergency
      department (ED) design on ED staff satisfaction and performance. BACKGROUND: High
      patient volume, surging workloads, and violent behaviors are expected pressures
      for ED staff. Literature suggests the substantial role of the physical
      environment in the delivery of care and its role in staff and patient
      experiences. Nevertheless, limited studies have explored simultaneous
      interactions between ED physical design elements, attributes (security,
      wayfinding, visibility, privacy, and efficiency), and staff satisfaction or
      performance. METHOD: Interviews, surveys, visibility graph analysis, and agent
      simulations were employed to understand the connection between ED physical
      design, attributes, performance, and staff satisfaction. RESULTS: Enhanced
      security, effective wayfinding, team visibility, noise reduction, adequate
      privacy, and accessible supplies and equipment were significant predictors of
      staff satisfaction and performance. Unobstructed views in waiting and triage and
      controlled entrances were critical for improving security. To improve wayfinding,
      eye-level signage, reducing surveillance obstacles, and creating direct public
      routes were recommended. Rectangular units with multiple perpendicularly
      connected corridors and linear pod arrangements enhanced movement. Including team
      rooms and enclosed ERs were recommended for privacy improvements. Visibility was
      critical for team communication and improved by including short-distanced
      perpendicular corridors and eliminating columns. Enhancing access to supplies or
      equipment and reducing noise levels improved the perception of staff efficiency.
      CONCLUSION: The findings contribute to the general body of knowledge on the
      impact of ED physical design on attributes that potentially improve staff
      satisfaction and work performance.

PMID- 30231639
TI  - Life History, Fertility, and Short-Term Mating Motivation.
AB  - The current research examines the impact of women's early-life socioeconomic
      status (SES; used as a proxy measure of life history strategy), relationship
      status, and ovulatory cycle phase on their desire for short-term mating. Results
      revealed that during the periovulatory phase (i.e., the high-fertility phase of
      the monthly ovulatory cycle), single women from low SES environments expressed an
      increased desire for short-term mating, whereas the opposite was found for single
      women from high SES environments. No such pattern was found for partnered women.
      These results suggest that one's early-life environment and relationship status
      may play a key role in how women respond to internal fertility cues, providing
      important new insights into factors that may moderate ovulatory shifts in mating
      behavior. Results provide some of the first evidence that one's developmental
      history may alter the expression of ovulatory cycle adaptations.

PMID- 30231640
TI  - Celebrity Opinion Influences Public Acceptance of Human Evolution.
AB  - The present research examined the influence of celebrity opinion upon
      individuals' acceptance of the theory of evolution. Priming stimuli were
      developed purveying pro-evolution, anti-evolution, or neutral opinion (Study 1).
      When paired with a male celebrity or expert source (Study 2), the male celebrity,
      but not the male expert, influenced undergraduates' acceptance of evolution. The
      influence of the male celebrity on acceptance of evolution was replicated in a
      community sample (Study 3). When paired with a female celebrity source,
      undergraduates' acceptance of evolution was similarly influenced (Study 4).
      Together, these findings extend our understanding of the reach of credible
      celebrity endorsers beyond consumer behavior to core individual beliefs, such as
      those surrounding the acceptance of human evolution.

PMID- 30231641
TI  - Severe hemolytic anemia due to transient acquired G6PD deficiency after ingestion
      of sodium chlorite.

PMID- 30231642
TI  - Effect of AAC partner training using video on peers' interpretation of the
      behaviors of presymbolic middle-schoolers with multiple disabilities.
AB  - Children require consistent responses from partners to their presymbolic
      behaviors in order to increase the frequency and variety of these behaviors and
      eventually build symbolic language. This study served as an initial attempt to
      evaluate the effect of AAC training on typically-developing peers' interpretation
      of the behavior of three students with multiple disabilities whose communication
      was presymbolic and idiosyncratic in nature. The study used a pretest-posttest
      control group design with 12 peers in each condition (i.e., experimental and
      control). During the pretest, peers in both groups were inaccurate in their
      interpretations of the behaviors of the students with multiple disabilities.
      During the posttest, peers who completed the training interpreted the behaviors
      of the students with multiple disabilities with statistically significantly
      higher accuracy than participants who did not complete the training. The training
      may be an effective intervention approach to increase the accuracy and
      consistency with which communication partners interpret the idiosyncratic
      behaviors of children with multiple disabilities. Future research should evaluate
      the efficacy of using such training to increase communication partners'
      identification of and responsivity to idiosyncratic behaviors within the context
      of real-world interactions.

PMID- 30231643
TI  - A critical synthesis of barriers and facilitators to the use of AAC by children
      with autism spectrum disorder and their communication partners.
AB  - The aim of this review was to critically synthesize barriers and facilitators to
      the use of AAC systems by children with autism spectrum disorder (ASD) and their
      communication partners. Qualitative data related to barriers and facilitators
      were synthesized from 42 studies located using a systematic search. A diverse
      range of studies was examined in order to identify the span of barriers and
      facilitators reported in the literature. Included studies comprised quasi
      experimental, non-experimental, and qualitative study designs. The full range of
      unaided, low-tech aided, and high-tech aided AAC systems were reported across the
      included studies. The critical synthesis identified 5 themes to which barriers
      and facilitators are related: (a) Intervention Services and Service Providers,
      (b) AAC Systems and Technologies (c), Communication Partners of Children with
      ASD, (d) Parents of Children with ASD, and (e) Children with ASD. The findings
      suggest that barriers and facilitators to the use of AAC vary across individuals,
      AAC modalities, and environments. By identifying barriers and facilitators to the
      use of AAC experienced by children with ASD and their communication partners,
      service providers might be better equipped to support these children and their
      communication partners. Clinical implications and future research directions are
      discussed.

PMID- 30231644
TI  - Quantitative proteomic analysis to the first commercialized liposomal paclitaxel
      nano-platform Lipusu revealed the molecular mechanism of the enhanced anti-tumor
      effect.
AB  - The first nano-platform commercialized as a drug delivery system was a liposomal
      formulation. The application of liposome technology resolved the issues of
      paclitaxel (PTX) insolubility and eliminated the use of solvents causing toxic
      side-effects, which enabled to apply higher drug doses leading to an enhanced
      drug efficacy. The growth-inhibitory activity of liposome-encapsulated PTX was
      retained in vitro against a variety of tumor cell. To investigate the drug
      efficacy in the system biological level, quantitative proteomic analysis was
      employed to study the molecular mechanism of the anti-tumor effect of Lipusu(r)
      (lip) compared with PTX on lung cancer cell A549. The functions of the
      differential expressed proteins were correlated to the negative effect to cell
      proliferation due to regulation of hippo pathway and prolonged cell cycle, as
      well as inhibitory cell exocytosis, which would cause the aggregation of free
      PTX. This investigation focused on the direct biological effect of lip to cancer
      cells. It was different from pharmaceutical issues about drug exposure, delivery
      and distribution which were widely investigated in other traditional studies. It
      was the first study about the drug effect of lip from the global molecular
      biological aspect.

PMID- 30231645
TI  - Fibroblasts from recurrent fibrotic overgrowths reveal high rate of proliferation
      in vitro - findings from the study of hereditary and idiopathic gingival
      fibromatosis.
AB  - PURPOSE: Investigate the content of fibrotic fibrils in gingival tissue and the
      proliferation of fibroblasts collected from recurrent and non-recurrent
      hereditary gingival fibromatosis (HGF) and idiopathic gingival fibromatosis
      (IGF). METHODS: Gingival biopsies were collected from HGF (n = 3) and IGF (n = 3)
      donors with recurrent and non-recurrent gingival overgrowths and from a control
      group (Ctrl, n = 3). Hematoxylin staining was performed to evaluate the
      histomorphology of gingival tissue. Heidenhain's AZAN trichrome staining served
      for visualization of fibrotic fibrils in gingiva. Quantitative analysis of the
      content of fibrotic fibrils in gingival tissue was performed using a polarized
      light microscope. Proliferation was evaluated at 24 h, 48 h, and 72 h in
      fibroblast cultures using a cell proliferation ELISA assay based on 5-bromo-2'
      deoxyuridine (BrdU). RESULTS: Numerous blood vessels and fibroblasts were
      observed in recurrent overgrowths, whereas moderate blood vessels and moderate to
      scanty fibroblasts were detected in non-recurrent overgrowths. Heidenhain's
      staining revealed numerous collagen fibers in both recurrent and non-recurrent
      overgrowths. Quantitative analysis in a polarizing microscope showed significant
      accumulation of fibrotic fibrils exclusively in the overgrowths with the
      recurrence. In all time-points, increased proliferation of cells from all
      recurrent overgrowths was observed, but not from overgrowths which do not
      reoccur. CONCLUSIONS: The study revealed that recurrent gingival overgrowths
      consist of highly fibrotic and dense connective tissue with numerous blood
      vessels and abundant fibroblasts. We also demonstrated that unlike fibroblasts
      derived from overgrowths, which did not present recurrence, fibroblasts derived
      from highly fibrotic and recurrent overgrowths maintain high rate of
      proliferation in vitro.

PMID- 30231647
TI  - Influence of punch geometry (head-flat diameter) and tooling type ('B' or 'D') on
      the physical-mechanical properties of formulation tablets.
AB  - The presented study assessed the influence of punch geometry (head-flat [HF]
      diameter) and tooling type ('B' or 'D') on the physical-mechanical properties of
      tablets prepared by direct-compression of two guaifenesin (25% or 40% w/w)
      formulations. Tablets of both formulations were prepared on instrumented, single
      layer, rotary tablet press using 10 mm, flat-faced, 'B' or 'D'-type tooling with
      different HF diameters, and compression forces (CF) ranging from 5 to 25 kN with
      5 kN increments. The tablets were evaluated for dimensions, weight variation,
      tensile strength (TS), friability, and capping index. In general, tablets
      prepared using 'D' tooling showed a significantly (p < 0.05) higher TS compared
      to those prepared using 'B' tooling, likely due to higher dwell-times associated
      with 'D' tooling. Formulations containing 25% w/w guaifenesin showed a
      significantly (p < 0.05) higher TS compared to those containing 40% w/w
      guaifenesin, at given compression CF, punch geometry, or tooling type. This could
      be due to the higher ratio of Prosolv(r) SMCC contributing to the
      compressibility. For both formulations compressed using 'B' tooling, differences
      in TS profiles were observed between different HF tooling. The TS of these
      tablets increased significantly with increasing HF diameter. For formulations
      compressed using 'D' tooling, this trend was observed only up to a CF of 15 kN,
      beyond which the TS plateaued, possibly due to work-hardening of the formulation
      at higher CF. These formulations also exhibited capping at CF above 15 kN and
      with higher HF diameters. The study showed a significant influence of punch
      geometry and tooling type on the physical properties of tablets.

PMID- 30231646
TI  - Synergistic effects of dual growth factor delivery from composite hydrogels
      incorporating 2-N,6-O-sulphated chitosan on bone regeneration.
AB  - A promising strategy to accelerate bone generation is to deliver a combination of
      certain growth factors to the integration site via a controlled spatial and
      temporal delivery mode. Here, a composite hydrogel incorporating poly(lactide-co
      glycolide) (PLGA) microspheres was accordingly prepared to load and deliver the
      osteogenic rhBMP-2 and angiogenic rhVEGF165 in the required manner. In addition,
      2-N,6-O-sulphated chitosan (26SCS), which is a synergetic factor of growth
      factors, was incorporated in the composite hydrogel as well. The system showed a
      similar release behaviour of the two growth factors regardless of 26SCS
      inclusion. RhBMP-2 loaded in PLGA microspheres showed a sustained release over a
      period of 2 weeks, whereas rhVEGF165 loaded in hydrogel eluted almost completely
      from the hydrogel over the first 16 days. Both growth factors retained their
      efficacy, as quantified with relevant in vitro assays. Moreover, an enhanced cell
      response was achieved upon the delivery of dual growth factors, compared to that
      obtained with a single factor. Furthermore, in the presence of 26SCS, the system
      revealed significantly upregulated alkaline phosphatase activity, human umbilical
      vein endothelial cell proliferation, sprouting, nitric oxide secretion, and
      angiogenic gene expression. This study highlighted that the composite hydrogel
      incorporated with 26SCS appears to constitute a promising approach to deliver
      multiple growth factors. From our findings, we could also conclude that rhBMP-2
      can promote angiogenesis and that the mechanism is worthy of further study in
      subsequent research.

PMID- 30231648
TI  - Cellular, matrix, and mechano-biological differences in load-bearing versus
      positional tendons throughout development and aging: a narrative review.
AB  - PURPOSE: Summarise available evidence comparing the cellular, biochemical,
      structural and biomechanical properties, and the changes that occur in these
      parameters in response to stimuli, in differentially loaded tendons across
      different stages of life. METHODS: The PubMed database was searched for
      literature pertaining to differences between tendons using the term "tendon" or
      "tendinopathy", plus one or more of the following descriptors: "loading",
      "positional", "weight- or load-bearing", and "energy-storing". The abstracts were
      reviewed and relevant full-length articles retrieved and used to assemble a
      narrative review. RESULTS: The incidence and prevalence of tendon disorders
      ("tendinopathies") is increasing in Western societies, with limited evidence that
      currently available treatments have any significant long-term effect on the
      disease course. A key emerging hypothesis is that disease in different tendons
      and even different regions within a tendon may be distinct. The available
      literature indicates that there are phenotypic differences, not only in the
      constitutive compositional and material properties but also in resident cells of
      positional compared with load-bearing tendons. Evident during early tendon
      growth, such differences have become well established by adulthood. CONCLUSIONS:
      The pheno-endotype of tendinopathy may be distinct between load-bearing tendons
      compared to positional tendons, which has translational implications with regard
      to preventing and managing tendinopathy. Better understanding of the molecular,
      cellular, and biomechanical pathophysiology underlying disease phenotypes, will
      allow more targeted/personalised treatment and therefore improve outcomes.

PMID- 30231649
TI  - Serum calcium derangements in neonates with moderate to severe hypoxic ischemic
      encephalopathy and the impact of therapeutic hypothermia: a cohort study.
AB  - BACKGROUND: Perinatal hypoxia is a recognized cause of hypocalcemia in neonates
      in the first 3 days of life. Therapeutic hypothermia (TH) promotes
      neuroprotection by decreasing calcium influx into the cells during the
      reperfusion phase thereby increase serum calcium levels. This study examines the
      trends of serum calcium levels in neonates with hypoxic ischemic encephalopathy
      (HIE) and the effect of TH. MATERIAL AND METHODS: A retrospective cohort study of
      neonates with moderate to severe HIE admitted to level III neonatal intensive
      care units (NICU's) in Calgary between September 2011 and October 2015. HIE was
      staged using modified Sarnat scoring system. Ionized calcium levels were followed
      in the first 3 days of age. RESULTS: One hundred thirteen neonates admitted with
      the diagnosis of moderate to severe HIE were included; 89 (79%) underwent TH.
      Hypercalcemia was significantly higher with TH 57 (64%) compared to 8 (33%) in
      noncooled group (p = .007). Hypocalcemia was less in TH group; 11 (12%) compared
      to 5 (21%) in non TH group. Hypo/hypercarbia did not alter the serum calcium
      levels. Furthermore; there was no increase in the incidence of intracranial
      hemorrhage, clinical or electrographic seizures, antiepileptic drug use, or
      hypoxic/ischemic MRI changes with calcium derangements. CONCLUSION: The incidence
      of hypocalcemia was reduced by almost half and hypercalcemia was significantly
      increased with TH in the first 3 days of life. The reduction in hypocalcemia and
      the increase in hypercalcemia may be attributed to the neuroprotective effect of
      TH.

PMID- 30231650
TI  - Multiple biomarker approach in the fiddler crab to assess anthropogenic pollution
      in tropical coastal environments.
AB  - CONTEXT: Fiddler crabs are important to the ecology of estuarine systems around
      the world, however, few studies have incorporated them as bioindicators. Urias
      estuary represents one of the most urbanized lagoons in the Gulf of California
      region and received discharges from different sources: shrimp farm,
      thermoelectric plant, fish processing plants, and untreated domestic and sewage
      wastes. OBJECTIVE: Assess the effects on anthropogenic contamination on female
      fiddler crabs reproduction, survival and genetic stability. METHODS: Exposition
      of wild crabs from a less impacted (reference) site to naturally contaminated
      sediments on under controlled laboratory conditions. Reproductive parameters,
      levels of DNA damage and mortality rates were measured, together with chemical
      analyses of sediments. RESULTS: The most contaminated sediments corresponded to
      the site where fish processing plants were located and the integrated biomarker
      response analysis revealed that the most adverse effects were produced by
      exposure to sediments from this site; these crabs showed higher mortality (67%)
      and poorer ovarian development than those crabs exposed to sediments from other
      sites. CONCLUSIONS: Female crabs under pollution stress are able to trade-off
      reproduction for survival, and surviving animals were able to restore genetic
      stability possibly by activating DNA repair mechanisms. Multiple biomarker
      approach discriminates different coastal contamination scenarios.

PMID- 30231651
TI  - Roadmap of molecular, compositional, and functional markers during embryonic
      tendon development.
AB  - Tendon is a specialized connective tissue that connects muscle to bone, thereby
      enabling musculoskeletal movement. Tendon injury leads to formation of tissue
      with aberrant functional properties. Current approaches to treat tendon injuries,
      including surgical repair and tissue engineering, have not achieved normal
      tendon. A roadmap of markers could help with identifying when mis-steps occur
      during aberrant tendon formation and providing instructions for normal tendon
      formation. We propose this roadmap should be based on the embryo-the perfect
      model of tissue formation. Our prior studies have shown that adult mesenchymal
      stem cells mimic tendon progenitor cell behavior when treated with tendon
      developmental cues. Although transcription factors and extracellular matrix
      molecules are commonly used to assess tendon development, we have shown that
      these markers do not reliably reflect functional property elaboration. Thus,
      evaluating tendon formation on the basis of a combination of these molecular,
      compositional, and functional markers is important. In this review, we highlight
      various tendon markers with focus on their temporal profiles and roles in tendon
      development to outline a roadmap that may be useful for informing tendon healing
      and tissue engineering strategies.

PMID- 30231653
TI  - A qualitative metasynthesis of the meaning of speech-generating devices for
      people with complex communication needs.
AB  - The aim of this metasynthesis review of published qualitative research was to
      investigate the lived experience and meaning ascribed to speech-generating
      devices (SGDs) by people with complex communication needs and their familiar
      communication partners. Bibliographic databases were searched up to June 2016,
      and selected articles were assessed for their relevance to the research aim. The
      metasynthesis included 21 original articles and resulted in the identification of
      six main themes, each of which was comprised of two or more sub-themes that
      related to the experience of using SGD: It's an Inefficient Voice, It's Not a
      Natural Voice, Making the Most of This Voice, It's My Voice, It's More Than a
      Voice, and Having a Voice: Being Heard. The findings depict how use of an SGD is
      a complex process of understanding the limitations of the device, acknowledging
      expectations of society, using strategies to optimize communication, being aware
      of what an SGD represents, and using the SGD to enable social participation and a
      sense of empowerment.

PMID- 30231652
TI  - Assessment of lisdexamfetamine dimesylate stability and identification of its
      degradation product by NMR spectroscopy.
AB  - Lisdexamfetamine dimesylate (LDX), a long-acting prodrug stimulant indicated for
      the treatment of the attention-deficit/hyperactivity disorder (ADHD), was
      subjected to forced degradation studies by acid and alkaline hydrolysis and the
      degradation profile was studied. To obtain between 10-30% of degraded product,
      acid and alkaline conditions were assessed with solutions of 0.01 M, 0.1 M, 0.5
      M, and 1 M of DCl and NaOD. These solutions were analyzed through 1 H NMR
      spectra. Acid hydrolysis produced no degradation in 0.01 M and 0.1 M DCl and
      4.38%, 9.69%, and 17.75% of degradation LDX, respectively, in 0.5 M, 1 M (4h) and
      1 M (4 + 12 h) DCl. And alkaline hydrolysis produced no degradation in 0.01 M and
      0.1 M DCl and a degradation LDX extension of 8.5%, 14.30%, and 22.91%,
      respectively, in 0.5 M, 1 M (4h) and 1 M (4 + 12 h) NaOD. LDX solutions subjected
      to 1 M (4 + 12 h) acid and alkaline hydrolysis were evaluated by NMR spectra (1 H
      NMR, 13 C NMR, HSQC and HMBC). LDX degradation product (DP) was identified and
      its structure elucidated as a diastereoisomer of LDX: (2R)-2,6-diamino-N-[(2S)-1
      phenylpropan-2-yl] hexanamide without their physical separation.

PMID- 30231654
TI  - Research on the relationship between cephalosporin structure, solution clarity,
      and rubber closure compatibility using volatile components profile of butyl
      rubber closures.
AB  - OBJECTIVE: Establish an effective experimental strategy to determine the
      compatibility of rubber closures for drugs. SIGNIFICANCE: Various types of rubber
      closures with different compositions are available for drug packaging. Many
      additives of rubber closures can be released from rubber closures and may affect
      the quality of drugs and pose a risk to human health. In this study, we aimed to
      determine the relationship between cephalosporin structure, solution clarity, and
      rubber closure compatibility using volatile components profile of butyl rubber
      closures. METHODS: Two opposite polarity gas chromatography (GC) systems and GC
      mass spectrometry (MS) were used to achieve rapid qualitative determination of
      the main volatile components in rubber closures. Simulated adsorption experiment
      was performed to investigate the adsorption of main volatile components in rubber
      closures by cephalosporins with different side chain structures, and to determine
      the effects of adsorption on solution clarity. RESULTS: A volatile components
      screening library of rubber closures was established and the structures of some
      volatile component were confirmed. The specific adsorption of the structure of
      cephalosporins on volatile components from rubber closures was studied.
      CONCLUSION: Based on the results of this study, rubber closures with good
      compatibility for cephalosporins with different side chain structures can be
      selected rapidly. This experimental strategy not only facilitates the screening
      of suitable rubber closures more effectively, but also enables the quick
      determination of volatile components adsorbed by drugs.

PMID- 30231655
TI  - Physicochemical characterization and thermal behavior of hexosomes containing
      ketoconazole as potential topical antifungal delivery system.
AB  - OBJECTIVE: The main purpose of this article is to show the valuable
      characteristics that liotropic liquid crystal systems possess to be employed as
      new drug delivery systems. SIGNIFICANCE: Colloidal aqueous dispersions of
      lyotropic liquid crystal mesophases such as the identified as cubosomes and
      hexosomes, and so on, have received considerable attention due to their unique
      nanostructures and their thermodynamic properties, which provide the potential as
      a sustained drug release matrix. Additionally, their large surface area and
      similarity with the liquid crystal structures of intercellular lipids of stratum
      corneum enhances the interaction with the skin and mucous, increasing the
      potential for topical drug delivery efficiency of biopharmaceutical class II
      drugs as the antifungal ketoconazole. METHODS: This article presents the results
      in morphological characteristics, particle size, zeta potential, flow, thermal
      behavior and drug release studies of hexosomes containing ketoconazole (LHLC-K)
      obtained with glycerol monooleate, propylene glycol monolaurate, poloxamer, and
      water mixtures. RESULTS: This colloidal system exhibits a Newtonian-type flow and
      a hexagonal nanostructure with a median particle size of 107 +/- 20 nm and zeta
      potential of +4.45 +/- 0.50 mV. Through differential scanning calorimetry
      studies, the LHLC-K demonstrated physical and chemical stability for more than
      six months and mesophasic thermal reversibility between 10 and 50  degrees C.
      Finally, LHLC-K releases ketoconazole following a kinetics described by the first
      order model. CONCLUSIONS: Physicochemical properties of the hexosomes containing
      ketoconazole are important for topical mycosis treatment administration,
      conditions of storage, and for its incorporation into the formulation of semi
      solid dosage forms.

PMID- 30231656
TI  - A national measure to reduce primary cesarean rates in Turkey.
AB  - PURPOSE: To examine the influence of the "Physician Unit Performance Coefficient"
      (PUPC) regulation, taken into force by the TR Ministry of Health in January 2013
      in our country, based on the cesarean rates in our clinic. METHODS: The pregnant
      women who gave birth at the Diyarbakir Maternity and Pediatrics Hospital within a
      period of three years before the PUPC has been taken into force and the pregnant
      women who have birth within a period of three years after January 2013, when the
      regulation has been taken into force, have been divided into two groups as Group
      1 and Group 2, respectively. Comparisons have been made between the two groups
      with respect to primary cesarean, total cesarean, neonatal mortality, and
      maternal mortality rates. RESULTS: From the 125,816 pregnant women who gave birth
      between February 2010 and January 2016, 58,856 (46.7%) are included in Group 1
      and the remaining 66,960 (53.3%) are in Group 2. The total Cesarean Rate is 27%
      in Group 2 and 24.8% in Group 1. The primary Cesarean Rate is 11.3% in Group 2
      and 13.5% in Group 1. The neonatal mortality rate is 7.810/00 in Group 2 and
      100/00 in Group 1. The differences in the total cesarean rates, primary cesarean
      rates and neonatal mortality rates have been found statistically significant.
      Maternal mortality rates have been found to be 5.1 in 100,000 in Group one and
      4.48 in 100,000 in Group 2 and the difference between the two groups has not been
      found as statistically significant. CONCLUSIONS: A meaningful reduction has been
      achieved in the primary cesarean rates without increasing maternal and neonatal
      mortality rates after the PUPC, implemented by the TR Ministry of Health, has
      been taken into force.

PMID- 30231657
TI  - Implementation of a standardized nurse initiated protocol to manage severe
      hypertension in pregnancy.
AB  - OBJECTIVES: Hypertensive disorders of pregnancy are a leading cause of maternal
      morbidity and mortality, studies have shown that standardized protocols for
      treating severe hypertension improves outcomes. Our goal was to examine the
      effects of a protocol for treating severe hypertension. METHODS: Using quality
      improvement methodology, we developed an evidence-based nurse-initiated protocol
      for management of severe hypertension. We used a before and after study design,
      with the primary outcome of time to administration of antihypertensive
      medications and time to achieve blood pressure control. Secondary outcomes
      included medication usage, time to repeat blood pressure, and proportion of women
      receiving appropriate treatment. Statistical analysis was completed with Stata,
      using data medians, 95% confidence intervals and a rank-sum test. RESULTS: Data
      was collected for 5 months before and 5 months after protocol implementation,
      with 67 patients included before and 125 patients after implementation. The
      median time to treatment of severe range blood pressure decreased from 25 min
      before to 11 min after protocol implementation, p <.001. Twenty-four% of women
      were treated within 15 min before and 60.6% were treated within 15 min after
      protocol implementation. Median time required to regain sustained mild range
      blood pressure was reduced from 45 min before to 41 min after protocol
      implementation, p = .004. 67.5% of women regained mild range blood pressure
      within 60 min before and 81.9% achieved blood pressure control within 60 min
      after protocol implementation. These improved outcomes were evident within the
      first month after protocol implementation and remained stable throughout the
      follow-up period. DISCUSSION: Implementation of an evidence-based nurse-initiated
      protocol for the treatment of severe hypertension in pregnancy decreases the time
      required to administer antihypertensive medication, time required to regain blood
      pressure control and nonbeneficial clinical variation. In addition, these
      benefits were achieved rapidly within a large hospital setting.

PMID- 30231658
TI  - Pregnancy managed by unfractionated heparin after mechanical aortic valve
      replacement.
AB  - Pregnancy after mechanical valve replacement involves high risk. Maternal valve
      thrombosis and hemorrhagic complications are associated with lethal outcomes;
      therefore, strict anticoagulant therapy is needed. Our patient was 26-year-old
      primiparous woman. She had undergone aortic valve replacement with a mechanical
      valve at 4 years of age and had used warfarin 3 mg per day since then. Because of
      her desire for a baby, she stopped warfarin and conceived spontaneously. She was
      referred to our hospital. After being informed of her choices, unfractionated
      heparin (UFH) administration was started. She experienced mild heart failure with
      sacroiliitis, bacteremia, and hematuria during pregnancy. She delivered her
      newborn at 37 weeks. Blood loss at delivery was 220 g. Administration of UFH was
      restarted 4 h after delivery and 3 mg of warfarin was administered from
      postpartum day (PPD) 6. Hemostatic suturing was required for vaginal bleeding on
      PPD7. A therapeutic dose of warfarin was achieved on PPD9. Although warfarin use
      is recommended as anticoagulant therapy for pregnant woman with mechanical
      valves, the safety and efficacy of UFH have not yet been clarified because of its
      limited use. More cases are needed to clarify this.

PMID- 30231659
TI  - Effects of mode of delivery on pro-oxidant/antioxidant balance in fetal
      circulation.
AB  - OBJECTIVE: This study was undertaken to assess the influence of mode of delivery
      on the balance between pro-oxidant/antioxidant systems in fetal circulation.
      MATERIALS AND METHODS: Both umbilical arterial and venous blood samples were
      obtained from 37 pregnant women who delivered by spontaneous vaginal delivery (VD
      group) and from 29 pregnant women who delivered by elective cesarean section (CS
      group). Oxidative stress and antioxidant activity were evaluated by reactive
      oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP),
      respectively. RESULTS: The d-ROMs values of the VD group were higher than that of
      the CS group in both umbilical arterial and venous blood and these differences
      were found to be statistically significant (p < .01 and p < .01, respectively).
      The BAP values of only the umbilical arterial blood were found to be
      statistically significant (p < .01), with values from the VD group being higher
      than those of the CS group. In all measurements, the d-ROMs values averaged below
      120 CARR U and BAP values averaged above 2200 umol/L. The ratio of BAP/d-ROMs
      difference was found to be statistically significant (p < .01) only in the
      umbilical venous blood, with ratios in the VD group being lower than those in the
      CS group. CONCLUSIONS: Our statistical analyses suggest that vaginal delivery has
      an effect on increasing oxidative stress as a result of the stress of labor and
      that an elective cesarean section does not impair the mother's oxidative stress
      status. Furthermore, the high BAP values in all the measurements suggest that
      neonates just after birth have the ability to cope with oxidative stress.
      Rationale   In many studies, the diversity of views on the influence of mode of
      delivery on the redox status of neonates is likely to be caused by the use of
      different biomarkers to measure either the oxidative stress, the antioxidant
      activity, or both. Furthermore, incomplete explanation for sampling cord blood in
      these studies, either arterial, venous blood or both, complicates matters. To
      solve the above, this study was designed to assess the effects of mode of
      delivery on both pro-oxidants, via d-ROMs, and antioxidants, via BAP, in both
      umbilical arterial and venous blood samples obtained just after birth. There are
      no existing studies of BAP in both umbilical arterial and venous blood to which
      we can refer. In conclusion, our study suggests that the pro-oxidant/antioxidant
      balance in neonates just after birth is better than may be expected when compared
      to the potentials of adults (including pregnant mothers) according to
      interpretations of BAP/d-ROMs. This can be understood that neonates may have
      already been endowed with the ability to cope with oxidative stress, as informed
      by high BAP values in both umbilical arterial and venous blood. Vaginal delivery
      may have an effect on increasing oxidative stress as a result of the stress of
      labors (as measured by d-ROMs), and an elective cesarean section, which has
      better BAP/d-ROMs in umbilical venous blood than that of vaginal delivery, may
      not impair the mother's oxidative stress status.

PMID- 30231660
TI  - Prediction of postnatal abnormal coiling of the umbilical cord in gestational
      diabetes mellitus: a diagnostic accuracy study.
AB  - OBJECTIVE: To investigate whether evaluations of antenatal umbilical coiling
      index (aUCI) could predict postnatal umbilical coiling index (UCI) (pUCI) in
      people with gestational diabetes mellitus (GDM) compared with normal pregnancy
      independent of maternal demographic and reproductive characteristics. METHOD: In
      this prospective study, 105 women with normal pregnancy, and 117 women with
      pregnancy complicated by GDM were recruited. Ultrasound scan of umbilical cord
      was performed at 18-23 and 37-41 weeks of gestation (WG). Evaluation of pUCI, as
      the reference standard, was performed within 24 hours after delivery. FINDINGS:
      There was no significant relationship between aUCI and maternal demographic and
      reproductive characteristics. The mean for pUCI was 0.21 +/- 0.12 in the GDM
      group, and 0.21 +/- 0.09 in the normal pregnancy (p = .61). In the GDM group, a
      significant association was found between aUCI and pUCI categories (p = .004).
      The area under curve (AUC) was less than 0.5 for hypocoiling in both groups. For
      hypercoiling it was 0.84 +/- 0.04 in the GDM group and 0.75 +/- 0.06 in the
      normal pregnancy group (18-23 WG). In the GDM group the cutoff points that
      predict hypercoiling were 0.28 (18-23WG), and 0.21 (37-41WG). These were 0.35 (18
      23WG), and 0.33 (37-41WG) in the normal pregnancy group. Diagnostic accuracy
      analysis revealed that in the GDM group, the sensitivity and specificity of
      hypercoiling for prediction of pUCI were 0.94 and 0.70 respectively at 18-23 WG.
      CONCLUSIONS: Antenatal hypercoiling at the second trimester of pregnancy strongly
      predict postnatal hypercoiling in pregnancies complicated by GDM.

PMID- 30231661
TI  - Three-dimensional volumetric study with VOCAL in normal and abnormal posterior
      fossa fetuses.
AB  - PURPOSE: The aim of this study was to compare volumetric parameters in the
      abnormal and normal posterior fossa using the Virtual Organ Computer-aided
      AnaLysis (VOCALTM) technique to determine whether fetuses with an abnormal
      posterior fossa have different volumes. METHODS: A prospective study was
      conducted on 17 fetuses with an abnormal posterior fossa including, Dandy Walker
      malformation (DWM) (n = 6), vermian hypoplasia (VH) (n = 3), mega cisterna magna
      (MCM) (n = 8), and 99 healthy control fetuses from 20 to 34 weeks' gestation.
      Measurement of the fetal cisterna magna and cerebellar volume was performed in
      the standard transcerebellar plane through the VOCALTM method. To establish the
      correlation of volumes with gestational age, polynomial regression analysis was
      performed. For comparison between groups, univariate ANCOVA was performed using
      gestational age as a covariate. The reliability was analyzed by the intraclass
      correlation coefficient (ICC). RESULTS: Cerebellar volume and cisterna magna
      volume were correlated with gestational age. Posterior fossa volume was
      significantly larger in DWM (p < .0001) and MCM (p < .0001) in comparison to the
      control group. In VH group, cisterna magna volume does not seem to expand (p =
      .298). Cerebellar volume does not seem to change in subgroups when the influence
      of gestational age is discarded (p = .09). The ratio of cerebellar volume to the
      cisterna magna volume decreases significantly in abnormal fetuses (p < .0001).
      Good intraobserver and interobserver reliabilities were found for both cerebellum
      and cisterna magna measurements. CONCLUSIONS: Volume analysis may have a role in
      discrimination of different posterior fossa pathologies.

PMID- 30231662
TI  - Prenatal diagnosis of fetal multiple hemivertebrae: the importance of 3D
      ultrasound assessment.
AB  - We herein present a case of fetal multiple hemivertebrae detected at antenatal
      sonography. The use of the 3 D technology supported by a new contrast enhancement
      rendering algorithm (Crystal Vue) has allowed the accurate prenatal
      classification of the defect, confirmed at follow up, that would have been
      difficult to define by 2 D only.

PMID- 30231663
TI  - Obstetrical and neonatal outcomes after a single episode of third-trimester
      vaginal bleeding ?.
AB  - OBJECTIVE: The objective of this study is to determine whether a single episode
      of vaginal bleeding occurring between 24 and 34 weeks gestation is associated
      with preterm delivery and other adverse maternal and neonatal outcomes. STUDY
      DESIGN: We conducted a retrospective cohort study in the Maternal-Fetal unit of
      two campuses of a large tertiary, medical center with approximately 12,000
      deliveries annually. The study group consisted of all women with a singleton
      pregnancy between 24 + 0/7 and 33 + 6/7 weeks of gestation, admitted to the high
      risk antenatal ward due to a single episode of vaginal bleeding of unknown origin
      between May 2003 and December 2014. Maternal and neonatal parameters of the study
      group were compared to the maternal and neonatal parameters of the rest of the
      singleton deliveries occurring in our institution during the study period. The
      primary outcome was rate of preterm delivery while secondary outcomes were other
      adverse maternal and neonatal outcomes. Multivariate logistic regression was
      performed to identify risk factors for preterm delivery in the study group.
      RESULTS: Two hundred thirty women met the inclusion criteria and 51,468 women
      were in the comparison group. Preterm delivery rates were 20% and 5.5% in the
      study and the comparison group, respectively OR = 3.55 [2.63-4.78] (p < .001).
      The aOR for preterm delivery among the study group for women with a previous
      preterm delivery was 4.62 [1.17-18.20] (p = .029) and for women with a short
      cervix was 9.35 [2.30-37.95] (p = .002). CONCLUSIONS: A single episode of third
      trimester vaginal bleeding is an independent risk factor for spontaneous preterm
      delivery. The presence of a shortened cervix or a history of a prior spontaneous
      preterm delivery increases this risk significantly. Key message Third trimester
      vaginal bleeding is strongly associated with preterm delivery. Knowledge of this
      relationship has valuable clinical implications for practicing obstetricians.

PMID- 30231664
TI  - Effects of Shuanghuanglian Injection on the activities of CYP1A2, 2C9, 2D6 and
      3A1/2 in rats in vivo and in vitro.
AB  - Shuanghuanglian Injection (SHLI), one of the most popular herbal prescription in
      China, has been commonly used to treat pneumonia, tonsillitis, and other
      respiratory diseases caused by bacterium and virus. This study is to investigate
      the effects of SHLI on the activities of Cytochrome P450 (CYP) 1A2, 2C11, 2D1 and
      3A1/2 in rats. Sixteen rats were randomly divided into two groups (SHLI-treated
      and blank control). They were administered SHLI or physiological saline for
      consecutive seven days. On day eight, sixteen animals were administrated cocktail
      drugs as probe substrates of the four CYP in vivo. In addition, other four probe
      drugs were added respectively into incubation systems of rat liver microsomes to
      assess the effects of SHLI on the four CYP isoforms in vitro. SHLI exhibited an
      inductive effect on CYP2C11 in vivo by decreasing Cmax, t1/2 and AUC0-infinity of
      tolbutamide, while the main pharmacokinetic parameters of caffeine, metoprolol
      and dapsone have no significant changes. In vitro study, SHLI showed no
      significant effects on the activities of CYP1A2, 2D1 and 3A1/2, but increasing
      the metabolism of tolbutamide in rat liver microsomes (RLM). SHLI induced the
      activities of CYP2C11, but had no significant effects on the activities of
      CYP1A2, CYP2D1 and CYP3A1/2 in rats.

PMID- 30231665
TI  - Absorption, Disposition and Metabolic Pathway of Amiselimod (MT-1303) in Healthy
      Volunteers in a Mass Balance Study.
AB  - 1. The absorption, metabolism and excretion of MT-1303 were investigated in
      healthy male subjects after a single oral dose of 0.4 mg [14C]-MT-1303
      (ClinicalTrials.gov NCT02293967). 2. The MT-1303 concentration in the plasma
      reached a maximum at 12 h after administration. Thereafter, the concentration
      declined with a half-life of 451 h. At the final assessment on Day 57, 91.16% of
      the administered radioactivity was excreted, and the cumulative excretion in the
      urine and faeces was 35.32% and 55.84%, respectively. 3. The most abundant
      metabolite in plasma was MT-1303-P, which accounted for 42.6% of the area under
      the plasma concentration-time curve (AUC) of the total radioactivity. The major
      component excreted in urine was Human Urine (HU)4 (3066434), accounting for 28.1%
      of radioactivity in the sample (4.05% of the dose), whereas MT-1303 was a major
      component in the faeces, accounting for 89.8% of radioactivity in the sample
      (25.49% of the dose) up to 240 h after administration. 4. This study indicates
      multiple metabolic pathways are involved in the elimination of MT-1303 from the
      human body and the excretion of MT-1303 and MT-1303-P via kidney is low.
      Therefore, MT-1303 is unlikely to cause conspicuous drug interactions or alter
      pharmacokinetics in patients with renal impairment.

PMID- 30231666
TI  - Percutaneous Cannulation for Extracorporeal Life Support in Severely and Morbidly
      Obese Patients.
AB  - BACKGROUND: Extracorporeal life support systems are well-established devices for
      treating patients with acute cardiopulmonary failure. Severe or morbid obesity
      may result in complications such as limb ischemia, bleeding, unsuccessful
      cannulation, or infection at the cannulation sites. This article reports on our
      experience with cannulation and associated complications in severely and morbidly
      obese patients. METHODS: Between January 2006 and September 2016, 153 severely or
      morbidly obese patients with a body mass index >35 kg/m2 were cannulated
      percutaneously for extracorporeal life support at our center. Among those, 115
      patients were treated with venovenous extracorporeal membrane oxygenation (VV
      ECMO) for acute lung failure and 38 patients with venoarterial extracorporeal
      membrane oxygenation (VA ECMO) for cardiogenic shock. Complications related to
      percutaneous access and long-term follow-up were analyzed retrospectively.
      Primary focus was on the success of cannulation, outcome, thrombosis, bleeding,
      limb ischemia, and infection at the cannulation site. Normal-weight patients
      receiving extracorporeal life support served as control. RESULTS: Percutaneous
      cannulation was successfully performed in all patients. Eighty-five (74%)
      patients were weaned from VV ECMO and 20 (52%) patients were weaned from VA ECMO.
      Limb ischemia requiring surgical intervention occurred in 5 (3%) patients,
      bleeding in 7 (5%) patients, and wound infection in 3 (2%) patients. In all other
      patients, decannulation was uneventful. These data as well as the long-term
      survival rates were comparable to those of normal-weight patients ( P > .05).
      CONCLUSION: Percutaneous vessel cannulation for extracorporeal life support
      systems is generally feasible. Therefore, percutaneous cannulation may well be
      performed in severely and morbidly obese patients. Patient outcome rather depends
      on appropriate support than on anatomy.

PMID- 30231667
TI  - TRIM59 regulates autophagy through modulating both the transcription and the
      ubiquitination of BECN1.
AB  - Macroautophagy/autophagy is a multistep cellular process that sequesters
      cytoplasmic components for lysosomal degradation. BECN1/Beclin1 is a central
      protein that assembles cofactors for the formation of a BECN1-PIK3C3-PIK3R4
      complex to trigger the autophagy protein cascade. Discovering the regulators of
      BECN1 is important for understanding the mechanism of autophagy induction. Here,
      we demonstrate that TRIM59, a tripartite motif protein, plays an important role
      in autophagy regulation in non-small cell lung cancer (NSCLC). On the one hand,
      TRIM59 regulates the transcription of BECN1 through negatively modulating the
      NFKB pathway. On the other hand, TRIM59 regulates TRAF6 induced K63-linked
      ubiquitination of BECN1, thus affecting the formation of the BECN1-PIK3C3
      complex. We further demonstrate that TRIM59 can mediate K48-linked ubiquitination
      of TRAF6 and promote the proteasomal degradation of TRAF6. Taken together, our
      findings reveal novel dual roles for TRIM59 in autophagy regulation by affecting
      both the transcription and the ubiquitination of BECN1. Abbreviations: ACTB:
      actin beta; BECN1: beclin 1; CHX: cycloheximide; CQ: chloroquine; GFP: green
      fluorescent protein; HA: haemagglutinin tag; His: polyhistidine tag; LC3B:
      microtubule associated protein 1 light chain 3 beta; NFKB: nuclear factor kappa
      B; NFKBIA: NFKB inhibitor alpha; NSCLC: non-small cell lung cancer; PIK3C3:
      phosphatidylinositol 3-kinase catalytic subunit type 3; RELA: RELA proto
      oncogene, NF-kB subunit; SQSTM1: sequestosome 1; tGFP: Turbo green fluorescent
      protein; TRAF6: TNF receptor associated factor 6; TRIM59: tripartite motif
      containing 59; B: ubiquitin.

PMID- 30231668
TI  - Anatomic Site-Specific Complication Rates for Central Venous Catheter Insertions.
AB  - BACKGROUND: Central venous catheter (CVC) complication rates reflecting the
      application of modern insertion techniques to a clinically heterogeneous patient
      populations are needed to better understand procedural risk attributable to the 3
      common anatomic insertion sites: internal jugular, subclavian, and femoral veins.
      We sought to define site-specific mechanical and duration-associated CVC
      complication rates across all hospital inpatients. METHODS: A retrospective chart
      review was conducted over 9 months at Georgetown University Hospital and
      Washington Hospital Center. Peripherally inserted central catheters and tunneled
      or fluoroscopically placed CVC's were excluded. Mechanical complications
      (retained guidewire, arterial injury, and pneumothorax) and duration-associated
      complications (deep vein thrombosis or pulmonary embolism, and central line
      associated bloodstream infections) were identified. RESULTS: In all, 1179 CVC
      insertions in 801 adult patients were analyzed. Approximately 32% of patients had
      multiple lines placed. Of 1179 CVCs, 73 total complications were recorded, giving
      a total rate of one or more complications occurring per CVC of 5.9%. There was no
      statistically significant difference between site-specific complications. A total
      of 19 mechanical complications were documented, with a 1.5% complication rate of
      one or more mechanical complications occurring. A total of 54 delayed
      complications were documented, with a 4.4% complication rate of 1 or more delayed
      complications occurring. There were no statistically significant differences
      between anatomic sites for either total mechanical or total delayed
      complications. CONCLUSIONS: These results suggest that site-specific CVC
      complication rates may be less common than previously reported. These data
      further inform on the safety of modern CVC insertion techniques across all
      patient populations and clinical settings.

PMID- 30231671
TI  - CD24 is required for regulating gene expression, but not glucose uptake, during
      adipogenesis.
AB  - Adipose tissue dysfunction in obesity and lipodystrophy results in major health
      complications such as heart disease and stroke, and is associated with an
      increased risk of some cancers. We have previously found that the cell surface
      receptor CD24 regulates adipogenesis as measured by lipid accumulation and gene
      expression in mature adipocytes. How CD24 regulates these processes remains
      unknown. To begin answering this question, we first determined that CD24 does not
      affect glucose uptake in differentiating adipocytes in vitro. We then examined
      changes in global gene expression via DNA microarray in 3T3-L1 adipocytes with
      siRNA-mediated knock-down of CD24 expression. We found that CD24 expression is
      necessary for upregulation of up to 134 genes. We validated the CD24-mediated
      regulation of 4 of these genes during in vitro adipogenesis of 3T3-L1 and primary
      cells isolated from the inguinal white adipose tissue depots of CD24 knockout
      mice. Surprisingly, we found that only 1 of these genes was also regulated by
      CD24 in cells from the epididymal depot. Overall, these data suggest that CD24 is
      necessary for select gene expression in a depot-specific manner during
      adipogenesis in vitro. These findings could help elucidate the mechanisms
      regulating lipid accumulation in adipocytes thereby aiding in the development of
      novel treatment strategies for obesity and lipodystophy.

PMID- 30231672
TI  - Positive Impact of Technician-Driven MTM Program on Performance Measures.
AB  - OBJECTIVE: To determine the effect of using a technician-driven medication
      therapy management (MTM) program on quality performance measures for a community
      pharmacy chain. METHODS: A technician-driven MTM program was incorporated in 35
      stores of a regional supermarket pharmacy chain. The overall chain percentage
      score for the 4 quality measures used in Medicare Part D Star Ratings-proportion
      of days covered (PDC) for cholesterol, diabetes, renin-angiotensin system
      antagonists (RASA), and high-risk medication use-was compared pre- and
      postimplementation of the technician-driven MTM program. Data were collected from
      Electronic Quality Improvement Platform for Plans and Pharmacies (EQuIPP)
      platform and t tests were used to analyze 1 year pre- and postimplementation.
      RESULTS: The PDC for RASA, high cholesterol medications, and diabetes medications
      significantly increased pre- to postimplementation for each drug class ( P <
      .001, P = .011, P = .001, respectively). The combined overall mean PDC score for
      RASA, cholesterol medications, and diabetes medication classes significantly
      increased by 5.6% from 2015 to 2016 (74.2% vs 79.8%, P < .001); there was also a
      nonsignificant decrease in high-risk medication use for the entire chain.
      CONCLUSIONS: This technician-driven MTM program can positively affect pharmacy
      quality performance and potentially improve patient outcomes.

PMID- 30231670
TI  - Critical role of mitosis in spontaneous late-onset Alzheimer's disease; from a
      Shugoshin 1 cohesinopathy mouse model.
AB  - From early-onset Alzheimer's disease (EOAD) studies, the amyloid-beta hypothesis
      emerged as the foremost theory of the pathological causes of AD. However, how
      amyloid-beta accumulation is triggered and progresses toward senile plaques in
      spontaneous late-onset Alzheimer's disease (LOAD) in humans remains unanswered.
      Various LOAD facilitators have been proposed, and LOAD is currently considered a
      complex disease with multiple causes. Mice do not normally develop LOAD. Possibly
      due to the multiple causes, proposed LOAD facilitators have not been able to
      replicate spontaneous LOAD in mice, representing a disease modeling issue.
      Recently, we reported spontaneous late-onset development of amyloid-beta
      accumulation in brains of Shugoshin 1 (Sgo1) haploinsufficient mice, a
      cohesinopathy-mediated chromosome instability model. The result for the first
      time expands disease relevance of mitosis studies to a major disease other than
      cancers. Reverse-engineering of the model would shed light on the process of late
      onset amyloid-beta accumulation in the brain and spontaneous LOAD development,
      and contribute to development of interventions for LOAD. This review will discuss
      the Sgo1 model, our current "three-hit hypothesis" regarding LOAD development
      with an emphasis on critical role of prolonged mitosis in amyloid-beta
      accumulation, and implications for human LOAD intervention and treatment.
      Abbreviations: Alzheimer's disease (AD); Late-onset Alzheimer's disease (LOAD);
      Early-onset Alzheimer's disease (EOAD); Shugoshin-1 (Sgo1); Chromosome
      Instability (CIN); apolipoprotein (Apoe); Central nervous system (CNS); Amyloid
      precursor protein (APP); N-methyl-d-aspartate (NMDA); Hazard ratio (HR); Cyclin
      dependent kinase (CDK); Chronic Atrial Intestinal Dysrhythmia (CAID); beta
      secretase 1 (BACE); phosphor-Histone H3 (p-H3); Research and development (R&D);
      Non-steroidal anti-inflammatory drugs (NSAIDs); Brain blood barrier (BBB).

PMID- 30231677
TI  - DIA Then and Now: A Half-Century Odyssey.

PMID- 30231674
TI  - Invasive Fungal Disease in Critically Ill Patients at High Risk: Usefulness of
      Lymphocyte Subtyping.
AB  - OBJECTIVES: This study aimed to investigate the distinguishing ability of
      lymphocyte subtyping for diagnosis and prognosis of invasive fungal disease
      (IFD). METHODS: We assessed lymphocyte subtyping and evaluated the quantitative
      changes in key immunological parameters at intensive care unit (ICU) admission in
      critically ill patients at high risk and their potential influence on diagnosis
      and outcome of IFD. The primary outcome was 28-day mortality. RESULTS: Among the
      124 critically ill patients with mean Candida score 3.89 (0.76), 19 (15.3%) were
      in the IFD group. CD28+CD8+ T-cell counts (area under the curve [AUC] 0.899, 95%
      confidence interval [CI], 0.834-0.964, P < .001) had better distinguishing
      ability than other immune parameters for IFD diagnosis. The cutoff value of
      CD28+CD8+ T-cell counts at ICU admission for IFD diagnosis was 59.5 cells/mm3,
      with 83.3% sensitivity and 86.4% specificity. Multivariate logistic regression
      analysis identified CD28+CD8+ T-cell count <59.5 cells/mm3 (odds ratio 59.7, 95%
      CI, 7.33-486.9, P < .001) as an independent predictor for IFD diagnosis.
      CD28+CD8+ T-cell counts could also predict 28-day mortality (AUC 0.656, 95% CI,
      0.525-0.788, P = .045). Kaplan-Meier survival analysis provided evidence that
      natural killer cell count <76.0 cells/mm3 (log-rank test; P = .001), CD8+ T-cell
      count <321.5 cells/mm3 (log-rank test; P = .04), and CD28+CD8+ T-cell count
      <129.0 cells/mm3 (log-rank test; P = .02) at ICU admission were associated with
      lower survival probabilities. CONCLUSION: CD28+CD8+ T-cell counts play an
      important role in early diagnosis of IFD. Low counts are associated with early
      mortality in critically ill patients at high risk of IFD. Our findings add
      evidence to the utility of lymphocyte subtyping in a diagnostic algorithm to
      better define IFD in critically ill patients at high risk.

PMID- 30231673
TI  - MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting
      inflammation and apoptosis through modulating TLR4/MyD88/NF-kappaB pathway.
AB  - Acute lung injury (ALI) is a critical clinical condition with a high mortality
      rate, characterized with excessive uncontrolled inflammation and apoptosis.
      Recently, microRNAs (miRNAs) have been found to play crucial roles in the
      amelioration of various inflammation-induced diseases, including ALI. However, it
      remains unknown the biological function and regulatory mechanisms of miRNAs in
      the regulation of inflammation and apoptosis in ALI. The aim of this study is to
      identify and evaluate the potential role of miRNAs in ALI and reveal the
      underlying molecular mechanisms of their effects. Here, we analyzed microRNA
      expression profiles in lung tissues from LPS-challenged mice using miRNA
      microarray. Because microRNA-27a (miR-27a) was one of the miRNAs being most
      significantly downregulated, which has an important role in regulation of
      inflammation, we investigated its function. Overexpression of miR-27a by agomir
      27a improved lung injury, as evidenced by the reduced histopathological changes,
      lung wet/dry (W/D) ratio, lung microvascular permeability and apoptosis in the
      lung tissues, as well as ameliorative survival of ALI mice. This was accompanied
      by the alleviating of inflammation, such as the reduced total BALF cell and
      neutrophil counts, decreased levels of tumor necrosis factor alpha (TNF-alpha),
      interleukin-1 (IL-6) interleukin-1beta (IL-1beta) and myeloperoxidase (MPO)
      activity in BAL fluid. Toll-like receptor 4 (TLR4), an important regulator of the
      nuclear factor kappa-B (NF-kappaB) signaling pathway, was identified as a novel
      target of miR-27a in RAW264.7 cells. Furthermore, our results showed that LPS
      stimulation increased the expression of MyD88 and NF-kappaB p65 (p-p65), but
      inhibited the expression of inhibitor of nuclear factor-kappaB-alpha (IkappaB
      alpha), suggesting the activation of NF-kappaB signaling pathway. Further
      investigations revealed that agomir-miR-27a reversed the promoting effect of LPS
      on NF-kappaB signaling pathway. The results here suggested that miR-27a
      alleviates LPS-induced ALI in mice via reducing inflammation and apoptosis
      through blocking TLR4/MyD88/NF-kappaB activation.

PMID- 30231678
TI  - Import Testing: An Outdated Practice? Opportunities for Improved Access to Safe
      and Efficient Medicines.
AB  - Import testing of medicines is performed in the middle of the legitimate supply
      chain when a product enters a country. Risks, however, are identified in the
      illegitimate supply chain and in the trade within a country. Hence, import
      testing does not add any significant value to the quality and safety of drugs nor
      reduces risks, provided the manufacturers apply good practices, for example, Good
      Manufacturing Practices (GMPs) and Good Distribution Practices (GDPs). The
      consideration to implement additional regulations does not correlate with the
      increasing convergence between National Regulatory Authorities (NRAs) and
      international harmonization, for example, Pharmaceutical Inspection Co-Operation
      Scheme (PIC/S) and International Council for Harmonisation (ICH). This
      publication reflects the historical application of import testing and today's
      practice, concerns, and misconceptions of this redundant procedure. It explains
      why postmarketing surveillance testing is better suited to control the quality of
      medicines, addressing highly relevant concerns: counterfeits and supply
      interruptions.

PMID- 30231679
TI  - Improving Investigative Site Contact Options on Clinical Trial Registries::
      Making It Easier for Patients to Find Clinical Trials.
AB  - BACKGROUND: Survey data has suggested a gap between individuals willing to
      participate in a clinical trial and those who enroll. Clearer research must be
      done to better understand this discrepancy and the accessibility of patient
      desired information, such that steps can be identified to assist sponsors in
      empowering patients to drive their own clinical trial search journey. METHODS:
      Patients, sponsors, and health care professionals were engaged through surveys
      and advisory boards to determine the ideal information for sponsors to provide
      during a clinical trial search. Public registries were analyzed to assess
      availability of basic investigator and site contact location information.
      RESULTS: Data reiterated the need for patients to have easy and unambiguous
      methods of connecting with the clinical trial site. Analysis of data on
      registries prove that sponsors have the opportunity to better utilize contact
      information on databases to enable a patient's clinical trial search journey.
      CONCLUSIONS: More robust disclosure of site location and contact details on
      public registries could lay the foundation for a more user-friendly clinical
      trial search. Allowing sites autonomy in site contact methods while promoting
      accessibility will facilitate the connection of interested patients with
      appropriate trial opportunities.

PMID- 30231680
TI  - Quantitative Assessment of Premium Rates for Clinical Usefulness in New Drug
      Price Calculation in Japan.
AB  - BACKGROUND: In Japan, the reimbursement price of a newly approved drug is
      calculated according to the rule established by the government. As an incentive
      to innovative Research & Development, a new drug that meets certain criteria
      obtains premiums on its price. To quantify the clinical value of new drugs in
      pricing, a point-based system was proposed by an academic study group. This paper
      gives the background to and overview of the system, and reviews the drugs that
      gained the premiums after its introduction. METHODS: For drugs to which premiums
      for innovativeness/usefulness were applied between April 2008 and August 2013,
      detailed information including the grounds for the premiums was identified. Then,
      subdivided factors for the requirement of the premium were set and points were
      allocated to them inductively depending on the degree of clinical impact.
      Finally, consistency between the rate actually applied and that calculated based
      on the system were reviewed for new drugs that gained the premiums after its
      introduction. RESULTS: Forty-seven drugs gained the premium for usefulness
      between April 2008 and August 2013. Based on the grounds for the premium, a point
      based system was established. After its introduction, 11 drugs gained premium for
      innovativeness/usefulness. The applied rates of premium were consistent with the
      calculated rate by the system in most cases. CONCLUSIONS: Predictability of
      future drug price is expected to be enhanced by the point-based system. As the
      control of health expenditure becomes strict, the importance of considering drug
      pricing policy that properly reflects the drug's clinical value increases.

PMID- 30231681
TI  - The Case for a Bayesian Approach to Benefit-Risk Assessment:: Overview and Future
      Directions.
AB  - The benefit-risk assessment of a new medicinal product or intervention is one of
      the most complex tasks that sponsors, regulators, payers, physicians, and
      patients face. Therefore, communicating the trade-off of benefits and risks in a
      clear and transparent manner, using all available evidence, is critical to ensure
      that the best decisions are made. Several quantitative methods have been proposed
      in recent years that try to provide insight into this challenging problem.
      Bayesian inference, with its coherent approach for integrating different sources
      of information and uncertainty, along with its links to optimal decision theory,
      provides a natural framework to perform quantitative assessments of the benefit
      risk trade-off. This paper describes the current state of the art in Bayesian
      methodologies for quantitative benefit-risk assessment, and how these may be
      leveraged throughout the life cycle of a medicinal product to support and augment
      clinical judgment and qualitative benefit-risk assessments. Gaps and potential
      new directions that extend the current approaches are also identified.

PMID- 30231683
TI  - Baseline Assessment of a Global Clinical Investigator Landscape Poised for
      Structural Change.
AB  - Mergers and acquisitions, the convergence of clinical research into clinical
      practice, more effective site selection and management practices, and efforts to
      improve investigator competence and credentials are all expected to contribute to
      consolidation in the global investigative site landscape during the coming 3 to 5
      years. Tufts CSDD conducted an analysis of the FDA's Bioresearch Monitoring
      Information System (BMIS) to gather baseline data with which to monitor this
      anticipated structural change. More than half-a-million records were analyzed on
      clinical investigators who have filed at least 1 form 1572 with the FDA annually
      between 2008 and 2015. The results show that the global landscape of unique FDA
      regulated principal investigators remains highly fragmented, nascent, and
      unstable. Principal investigators who file the lowest volume of 1572 forms each
      year make up the highest proportion of the global landscape, and one-third of all
      principal investigators each year are first-time filers. Each year, 40% of
      principal investigators drop out of the clinical research enterprise. However,
      there are signs that the landscape is beginning to scale and mature, particularly
      among investigators in North America. In addition, the rate of globalization is
      slowing and shifting, where recent growth in the number of active principal
      investigators in Europe has outpaced that in North America and in the rest of
      world. The implications of this study and future areas of research are discussed.

PMID- 30231682
TI  - Comparison of New Drug Accessibility and Price Between Japan and Major European
      Countries.
AB  - BACKGROUND: A common concern about universal health insurance coverage is how to
      control health expenditure. The escalation of health care costs raises public
      awareness of the optimization of drug price and increased demand for cost
      effectiveness assessment. In this paper, we show the differences in patient
      access to new drugs and drug price among countries, in which the situation of
      introduction of cost-effectiveness assessment scheme is different. METHODS: We
      investigated the health insurance coverage proportion of newly approved drugs in
      Japan, France, Germany, and the United Kingdom (UK). Then, we calculated the
      ratios of the European to the Japanese price for products that were reimbursed in
      both countries. RESULTS: Japan had the highest health insurance coverage
      proportion (98.6%) in the 4 countries. In Japan, all the drugs that were approved
      in 2015 had been already listed in the latest formulary of February 2016. As for
      drug price, there wasn't much difference between Japan and the European countries
      in many cases. CONCLUSION: From the viewpoint of the health insurance coverage
      proportion and the speed of reimbursement decision, the hurdle to access new
      drugs in Japan is lower than that in major European countries. While extensive
      coverage of health insurance and prompt reimbursement decision lower the hurdles
      to access new drugs and expand treatment options, they could lead to the
      increased medical expenditure. We should continue to discuss sustainable health
      insurance systems and drug price calculation schemes that properly reflect the
      drug's clinical value while keeping the availability of new drugs to patients.

PMID- 30231684
TI  - The Benefit-Risk Assessment of Medicines: Experience of a Consortium of Medium
      Sized Regulatory Authorities.
AB  - BACKGROUND: In 2008, a consortium of 4 regulatory authorities, the Australian
      Therapeutic Goods Administration (TGA), Health Canada, Swissmedic, and Singapore
      Health Sciences Authority (HSA) approached the Centre for Innovation in
      Regulatory Science (CIRS) to support the development of a benefit-risk framework
      and template that could be used by all 4 authorities and that would enable joint
      and shared reviews to maximize resources. CIRS facilitated this collaboration,
      the Consortium on Benefit-Risk Assessment (COBRA), between 2008 and 2013.
      METHODS: COBRA developed a benefit-risk assessment template based on the EMA
      reflection paper of 2008, which was constructed and then evaluated in 3 phases: a
      feasibility study, a retrospective pilot study, and a prospective study. The
      final template corresponded to the Universal Methodology for Benefit-Risk
      Assessment (UMBRA) developed by CIRS. RESULTS: By 2014, elements of the template,
      which had been developed during the program of work, aided the authorities in
      documenting the benefit-risk assessment of medicines in a systematic and
      structured way. However, its role in the individual authority's assessment
      toolkit was influenced by the number of key elements within the template that
      were already included in their current clinical assessment templates. Notably,
      the agencies indicated that they will modify their clinical assessment templates
      to align with the UMBRA 8-step framework approach. CONCLUSIONS: Overall, the
      authorities believed that the project had given them a better understanding of
      the value of using a structured approach to the benefit-risk assessment of
      medicines as well as enabling shared learnings between the authorities.

PMID- 30231685
TI  - Best Practices for Submitting Promotional 2253 Submissions in the New Module 1
      Specification.
AB  - June 2016 marks 1 full year since the optional implementation of US Module 1
      Specification v2.3. Since its release, pharma companies have dealt with expanded
      submission-level metadata fields, the ability to submit advertising and
      promotional submissions, and more rigid validation criteria. Prior to
      transitioning, sponsors must ensure their building and validating tools are up-to
      date, that a system is in place to integrate departments working together for the
      first time, and that all guidance documents are understood and implemented.
      Sponsors now can group submissions across application types, which will help save
      rework across submissions. Looking at one submission type now accepted in eCTD,
      this paper will explore the new functionality that has created new possibilities
      and challenges for Regulatory Operations.

PMID- 30231686
TI  - On a Stepwise Quantitative Approach for Benefit-Risk Assessment.
AB  - The field of structured benefit-risk assessment has evolved rapidly in the last
      few years with a great deal of regulatory and industry-wide initiatives. The
      available structured approaches to benefit-risk assessments exhibit and share
      many common elements in terms of defining the decision problem and therapeutic
      context, identifying key benefit and risk factors, and interpreting and
      communicating benefit-risk findings. However, there is limited guidance with
      these initiatives that is specific to metrics and methods to conduct benefit-risk
      assessment. Although we agree that benefit-risk metrics and analysis methods may
      be specific to individual clinical settings, we believe that there are general
      principles that can be followed. In this article, we propose a stepwise
      quantitative approach for benefit-risk assessment. We applied the stepwise
      quantitative approach to 3 real case studies.

PMID- 30231687
TI  - Optimizing the Use of Electronic Data Sources in Clinical Trials: The Technology
      Landscape.
AB  - TransCelerate has created an initiative to facilitate the industry's movement
      toward optimal use of electronic data sources for clinical research. Although
      guidance and standards have been in place for some time, gaps remain.
      Consequently, transcription among electronic systems continues to be the norm. In
      the initial phase of the eSource Initiative, TransCelerate is developing a
      thorough understanding of the current landscape. As a preliminary step in this
      process, the TransCelerate eSource Initiative published Optimizing the Use of
      Electronic Data Sources in Clinical Trials: The Landscape Part I, which provided
      insight into sponsor company eSource activities and the environment affecting
      eSource adoption based on input from TransCelerate member companies, standards
      organizations, and regulatory authorities. For Part II (this article),
      TransCelerate surveyed technology companies, including CROs providing technology,
      to better understand capabilities available today, plans for eSource, and
      perceived barriers to greater adoption. This information is a vital input that
      will help shape upcoming TransCelerate proposals for best practices for industry
      utilization of electronic data collection tools and methods. It is clear from the
      survey results that the technologies needed to support the various eSource
      modalities are mature. However, the approach to implementing eSource is
      fragmented. Greater collaboration is needed not only within the pharmaceutical
      industry but across industries that include health care and technology. The
      industry must reach common understandings about novel endpoints, data standards,
      system validation, and related issues. While technology in itself is not a
      significant barrier to eSource implementation, interoperability among systems is
      an enormous challenge to establishing a complete end-to-end electronic health
      care and research ecosystem. The TransCelerate eSource Initiative will continue
      to evaluate the technology, regulatory environment, data standards, and health
      care landscape to support the goal of improving global clinical science and
      global clinical trial execution. Forthcoming publications will focus on future
      vision and demonstration projects.

PMID- 30231688
TI  - Drugs Targeted for Price Cutting in Japan: The Case of Price Revisions Based on
      the Divergence of Official Versus Delivery Prices.
AB  - BACKGROUND: Official drug prices have been set by the government and revised
      every other year in Japan. However, most drug prices are revised based on the
      price divergence rate of official and delivery prices every other year. This
      paper overviews how the drug price revision process works and reveals factors
      associated with price cutting, based on the price divergence rate. METHODS: Drugs
      approved as new molecular entities from 2005 to 2014 were selected for price
      cutting analysis, based on the price divergence rate. Logistic regression
      assessed the determinants of whether drugs were targeted for price cutting in
      2016. Additionally, generic drugs approved from 2009 to 2013 and their off-patent
      drugs were also analyzed by multiple linear regression analysis to reveal
      determinants related to price divergence rates. RESULTS: From the targeted on
      patent drugs, 90% were targeted for price revision based on the price divergence
      rate. Of these drugs, 23% were targeted for price cutting. Drugs whose
      characteristics are larger sales, lower cost/patient, being followers, and being
      longer in the market were more likely to be targeted for price cutting. The
      number of generic manufacturers is directly proportional to the price cutting of
      both generic and off-patent branded drugs. CONCLUSIONS: As drug price revision
      policy is under reconstruction in Japan, the characteristics of drugs targeted
      for price cutting shown in this study should be considered for establishing drug
      price revision policies that reflect market conditions adequately.

PMID- 30231689
TI  - Investigation of the Factors Affecting Risk-Based Quality Management of
      Investigator-Initiated Investigational New-Drug Trials for Unapproved Anticancer
      Drugs in Japan.
AB  - BACKGROUND: With an increase in the complexity and cost of clinical trials and
      the advances in information technology, monitoring guidance issued by regulatory
      authorities recommends risk-adapted monitoring. To introduce the monitoring
      method for investigator-initiated investigational new drug (IND) trials using
      unapproved anticancer drugs, we performed exploratory retrospective analyses to
      identify risk factors for data quality. METHODS: To select investigator-initiated
      IND trials using unapproved anticancer drugs, we set the trial selection
      criteria. Data collection was performed by using audit trails and monitoring
      reports. Collected data were analyzed by univariate and multivariate analyses to
      identify the independent risk factors related to error. RESULTS: By trial
      selection criteria, 5 investigator-initiated IND trials using unapproved
      anticancer drugs were selected. The error rates of the total data, critical data,
      and noncritical data were 7.4%, 9.7%, and 5.9%, respectively. There was no
      difference between clinical research core hospitals certified by the Ministry of
      Health, Labour and Welfare and other hospitals in univariate analysis (odds ratio
      [OR], 1.00; 99% confidence interval [CI], 0.96-1.05; P = .9179). As the main
      independent risk factors related to error, critical data in the importance of
      data (OR, 1.28; 99% CI, 1.24-1.33; P < .0001) and groups with <=3 patients after
      registration (OR, 1.12; 99% CI, 1.10-1.15; P < .0001) were significantly related
      to errors in multivariate analysis. CONCLUSIONS: The results of this research
      suggest that the feasibility of risk-based monitoring and sampling source data
      verification was indicated for noncritical data and patients after the third
      case.

PMID- 30231690
TI  - Improving Information Exchange with Clinical Trial Participants: A Proposal for
      Industry.
AB  - BACKGROUND: Researchers are increasingly motivated to move toward patient-centric
      drug development. TransCelerate has identified improved "information exchange" as
      an important component of creating a more satisfying clinical trial experience
      for patients and their health care professionals (HCPs). METHODS: Patients,
      sponsors, sites, and HCPs were engaged through surveys, interviews, and/or
      advisory boards to capture the current status of information exchange and
      identify possible future practices between the major stakeholders within the
      clinical research ecosystem. RESULTS: Data suggest that patients have numerous
      desires and preferences for information exchange during their clinical trial
      journey that are not commonly met. Various opportunities exist to improve the
      clinical trial participants' experiences by improving information exchange
      practices across various stages of the participant's journey. CONCLUSIONS: A
      shift in industry focus toward more comprehensive information exchange with trial
      participants has the potential to positively impact many patients.

PMID- 30231691
TI  - Analysis of Review Times for Recent 505(b)(2) Applications.
AB  - BACKGROUND: Annual review statistics released by the Food and Drug Administration
      (FDA) and a number of studies indicate that the review process improvements
      introduced under various versions of the Prescription Drug Use Fee Act (PDUFA)
      have been successful in decreasing average times for marketing approval of new
      molecular entities (NMEs). Similar statistics are not available, however, for non
      NME new drug applications. These application types, such as those covered under
      section 505(b)(2) of the Food and Drug and Cosmetic Act, represent more than half
      of all new drug application (NDA) submissions annually and they are primarily
      based on previously approved drugs. To our knowledge, this is the first study to
      gather review statistics on 505(b)(2) designations. METHODS: For this study, we
      analyzed total review times and review designations for 284 505(b)(2) NDA
      approvals between 2009 and 2015. RESULTS: Our results show that overall, the
      505(b)(2) regulatory pathway results in longer review time than for NMEs despite
      the intent of the 505(b)(2) designation to simplify and streamline the review
      process. Several illustrative examples and the implications are discussed.
      CONCLUSIONS: For drug developers, the important take home message is that-as for
      any program at the FDA-shorter review times and fewer FDA requirements under a
      505(b)(2) designation should not be anticipated or expected. The study results
      serve as benchmark data providing insights into regulatory submission strategy
      and planning.

PMID- 30231692
TI  - Improving Patient Involvement in Medicines Research and Development:: A Practical
      Roadmap.
AB  - The value of patient involvement (PI) in medicines research and development (R&D)
      is increasingly recognized by all health stakeholders. Despite numerous ongoing
      PI initiatives, PI so far lacks structure and consistency in approach. Limited
      formal documentation of PI activities further hampers the sharing of experience
      and learnings, preventing timely and systematic implementation. This article
      summarizes the outcomes of several multistakeholder discussions during 2013-2016
      in a practical roadmap for PI in medicines R&D. The roadmap highlights specific
      opportunities for PI along the 4 key stages of the medicines R&D life cycle and
      is illustrated with concrete examples. This roadmap's aim is to provide a tool to
      facilitate PI during medicines research and development and is being shared to
      encourage implementation and further refinement.

PMID- 30231693
TI  - Editor in Chief's Comment: External Validity in Systematic Reviews.

PMID- 30231694
TI  - MicroRNA-19b Promotes Nasopharyngeal Carcinoma More Sensitive to Cisplatin by
      Suppressing KRAS.
AB  - MicroRNAs have been reported to play a vital role in diverse biological processes
      and tumorigenesis. MicroRNA-19b-5p has been observed to be downregulated in other
      cancers, but the function of microRNA-19b-5p in human nasopharyngeal carcinoma
      has not been well investigated. In our study, these results demonstrated that
      microRNA-19b-5p was significantly downregulated in 37 pairs of nasopharyngeal
      carcinoma tissues when compared to normal tissues. Enforced expression of
      microRNA-19b-5p inhibited activity of cell proliferation and cell migration of
      nasopharyngeal carcinoma cancer cells, CNE1 and HNE1. Furthermore, microRNA-19b
      5p targeted KRAS proto-oncogene, GTPase in cancer cells. In human clinical
      specimens, KRAS was higher expressed in cancer tissues when compared with normal
      tissues, which was inversely correlated with the expression of microRNA-19b-5p.
      More interestingly, microRNA-19b-5p sensitizes CNE1 cells to cisplatin by
      inhibiting its target KRAS. Finally, microRNA-19b-5p inhibits tumorigenesis in
      vivo. Thus, our results investigated that microRNA-19b-5p functioned as a tumor
      suppressor and indicated its potential application for the treatment of human
      nasopharyngeal carcinoma in future.

PMID- 30231695
TI  - Advances in Clinical Research in Ecuador.
AB  - Ecuador is undergoing a process of clinical research development and
      strengthening. At the turn of the century, Ecuador experienced a favorable
      transition period of economic stability, which enabled advances in the health
      system and improvements in population welfare indicators. During this period,
      Ecuador created an institutional infrastructure to support the implementation and
      development of research projects. In turn, Ecuador created institutions,
      including the National Agency for Health Regulation, Control, and Surveillance
      (Agencia Nacional de Regulacion, Control y Vigilancia Sanitaria [ARCSA]), and
      regulations establishing clinical trial (CT) design, conduct, recording, and
      reporting parameters, whose compliance ensures the protection of the rights of
      research subjects and requires compliance with Good Clinical Practice (GCP).
      Ecuador has favorable conditions for fostering the development of clinical
      research. The regulation of CTs is a process undergoing consistent changes toward
      harmonization with international standards and quality assurance.

PMID- 30231696
TI  - Phase 1: An Upcoming Series of White Papers for Successful Early Clinical
      Development.

PMID- 30231697
TI  - The Impact of Innovation: How the Changing Nature of Data Will Challenge FDA's
      Regulatory Framework.
AB  - Rapid advances in technology and our understanding of disease will lead to a
      shift in how the health care system thinks about data, which will in turn
      challenge current regulatory constructs. In the future, there will be a shift
      away from milestone-based data to continuous, contextual data; we believe this
      data shift will impact the current model of medical product regulation, with
      potential implications across the regulatory landscape, reflecting the
      convergence of clinical development and clinical practice.

PMID- 30231698
TI  - Using Off-Label Communications to Responsibly Advance the Public Health.
AB  - The debate over off-label communications doesn't begin or end with the Caronia or
      Amarin decisions. It's a continuing dialogue between manufacturers and the FDA,
      between doctors and patients, between doctors and academics, between lawyers and
      judges, and between advocates on all sides. And the red thread that ties these
      conversations together is responsible off-label communications. Not sales
      strategies. Not Direct-to-Consumer (DTC) advertising and marketing tactics. Not
      managed market negotiations-the responsible sharing of truthful and accurate
      information via nonregulated speech. Off-label communications, properly done,
      advances precision medicine, delivering speedier positive patient outcomes and
      reducing costs to our health care system. Off-label communications provides
      patients with more options for effective medicines.

PMID- 30231699
TI  - Our Annual Meeting Is Fast Approaching: Chicago Here We Come!

PMID- 30231700
TI  - Reducing Call Volume at Medical Information Centers by Switching to a Web-Based
      Self-Service Facility-What to Consider? Providing Customers With Digital Medical
      Information on the Internet.
AB  - BACKGROUND: Medical Information Centers (MedInfo Centers) at pharmaceutical
      companies receive a high volume of requests for product-related information.
      While this service is generally restricted to working hours, the use of a web
      based self-service portal allows provision of information 24 hours a day 7 days a
      week (24/7). METHODS: In 2012 Sanofi (Frankfurt, Germany) launched their web
      based self-service portal, which provides Medical Information for all Sanofi
      products in a nonpromotional manner. Here, we present data on the background and
      evolution of the service over time, as well as the rate of acceptance by
      pharmacists, physicians, and patients. RESULTS: In the pilot phase of portal
      development (July 2012-January 2013), we provided information such as the summary
      of product characteristics (SmPC) and a list of frequently asked questions
      (FAQs). These were subsequently followed by patient information leaflets (PILs),
      as of February 2013. While SmPCs and FAQs were initially password protected,
      German drug law allowed us to make the PILs and SmPCs openly available in
      February 2013. Once content was obtainable without authentication, a good uptake
      of the online service for accessing both SmPCs and PILs was observed, while FAQs
      were initially less popular. Subsequent redesign of the user interface, provision
      of more access options and revision of content based on search engine
      optimization was able to substantially increase the use of FAQs. The web-based
      self-service portal led to the number of MedInfo Center requests falling by about
      20% within the observation phase, with a corresponding increase in the use of web
      based self-service. CONCLUSION: The increasing demand for 24/7 information
      coupled with the wide accessibility of the Internet has led to a movement toward
      redirecting information requests received by pharmaceutical companies to the web.
      We have found that, wherever possible, publishing information in open-access
      areas and keeping the navigation simple are key factors in the success of this
      service.

PMID- 30231701
TI  - Introduction to the Special Section: Phase I Clinical Trials.

PMID- 30231702
TI  - Development of the Observable Behaviors of Autism Spectrum Disorder Scale.
AB  - BACKGROUND: The objective of this research was to develop a caregiver-reported
      clinical outcome assessment (COA) measure designed to assess observable behaviors
      of children, ages 4 to 12 years, with autism spectrum disorder (ASD) for
      supporting labeling claims of treatment benefit. METHODS: Development of the
      measure included a review of the literature and existing instruments, conceptual
      disease model development, concept elicitation focus groups, item generation, and
      cognitive debriefing interviews. RESULTS: Predominant characteristics and
      behaviors of ASD identified by the literature and instrument reviews included
      sociability, communication deficits, stereotypy, inattention and hyperactivity,
      irritability, anxiety, and familial impact. In each of the 10 instruments
      reviewed, evidence of content validity was limited or nonexistent. Predominant
      themes arose across 8 major categories during concept elicitation. A total of 27
      concepts were identified through focus group feedback and formed the basis for
      item development and cognitive pre-testing. Revisions to the items yielded a
      final version of a daily diary containing 21 items assessing observable behaviors
      and characteristics of ASD in children 4 to 12 years old. CONCLUSIONS: The
      Observable Behaviors of ASD Scale (OBAS) was developed as a self-administered,
      caregiver-reported measure containing 8 predominant themes. Items are scored on
      one of two 5-point ordinal categorical response scales, and the recall period for
      each item is "the past 24 hours." This research provides evidence that the OBAS
      is content valid for assessing treatment benefit, which was found to be lacking
      in other instruments.

PMID- 30231703
TI  - Special Populations in Clinical Pharmacology Studies: Evolving Challenges.
AB  - The clinical research industry is changing, and the number of protocols requiring
      specialty populations for early-phase clinical studies is increasing. In
      particular, the demand for studies on renal specialty populations has grown,
      given the prominent role of the renal system in excreting drugs from the body.
      Understanding the challenges associated with the use of specialty populations is
      critical to ensure that the study design will allow for the timely and successful
      completion of the project, while minimizing costs and safety risks.

PMID- 30231704
TI  - Describing the Endpoint: Consistency Across Protocols, Study Reports, Postings,
      and Publications.
AB  - Endpoints are the cornerstone of clinical trial design and are the critical
      elements for evaluating the success of a clinical study. Endpoints are
      communicated in clinical protocols, study reports, study registration and result
      posting sites, as well as publications. It is, therefore, important that
      endpoints are presented consistently, correctly, and completely. The FDAAA Final
      Rule expectations of describing endpoints in specific terms provides a way to
      keep this consistency across all documents.

PMID- 30231705
TI  - Hot Button Protocol and Operational Issues Between Sponsors and Sites in Clinical
      Pharmacology Studies: A Moderated Forum Session.
AB  - This paper summarizes a discussion that took place at the 52nd Annual DIA Meeting
      in Philadelphia, PA, on June 30, 2016, titled "Hot-Button Protocol and
      Operational Issues between Sponsors and Sites in Clinical Pharmacology Studies."
      The symposium was a moderated panel of phase 1 clinical research experts
      representing the sponsor, and investigational sites. Conference attendees of
      similar experience joined in the discussion after commentary by each panelist.
      The learning objectives of the symposium were (1) to recognize issues that can
      provoke sponsor/site conflict or diminish conduct efficiency when they arise in
      the course of preparing to conduct or execution of phase 1 clinical studies, (2)
      to discuss how to handle such issues with counterparts when they arise and
      describe ways to negotiate and formulate a successful resolution. Sponsors and
      sites both have challenges in executing clinical trials on time and within
      budget. Both need to set and maintain realistic expectations and communicate with
      honesty, transparency, and timeliness. Achieving this goal will advance the more
      important take-away message, that developing new drugs requires sound execution
      of clinical trials.

PMID- 30231706
TI  - Safety in FIH Trials: A Summary of the Symposium "Fatal Drug Trial in Phase 1:
      Understanding Risk, Subject Safety, Timelines, and Cost".
AB  - A cross-section of clinical research professionals convened at the June 2016 Drug
      Information Association annual meeting in Philadelphia to discuss and critically
      analyze the first-in-human (FIH) clinical trial conducted by a French CRO with
      BIA 10-2474 (BIA) under development for pain relief by Bial-Portela & Ca., S.A.,
      that resulted in 6 healthy volunteers hospitalized with serious adverse events,
      which resulted in 1 death. This paper summarizes the background, presentations,
      and discussion points of Symposium no. 107 in an effort to share the learnings of
      our symposium with others who conduct studies. Novel investigational products
      studied in phase 1 clinical trials propose a heightened risk of adverse events
      that may not be foreseeable when relying on animal studies to project outcomes in
      humans. Novelty of molecular structure, drug class, mechanism of action, proper
      dose selection, pharmacokinetics, and therapeutic window are all contributing
      factors that heighten risks when transitioning from animal to human trials. The
      potential for catastrophic events confronts every sponsor/investigator in
      clinical trials. Minimizing risks to subjects is an essential ethical and
      scientific mandate for all those involved in the clinical trials. A complex
      matrix of planning, conducting, and communicating preclinical and clinical
      observations need to be considered carefully by the Sponsor, Investigator and
      others during the planning, execution, and interpretation of FIH studies, in
      order to promote participant safety and study data integrity. Suggestions may be
      applied to FIH studies, which may provide a new or improved way to address
      complex system and prevent or mitigate situations such as what occurred with the
      Bial FIH trial, where seemingly a number of issues coincided in a "perfect storm"
      and the system failed to sound a warning or detect an issue before a life was
      tragically lost.

PMID- 30231707
TI  - A Comparison of PMDA and EMA Consultations for Regulatory and Scientific Matters
      in Drugs and Regenerative Medicine Products.
AB  - The Pharmaceuticals and Medical Devices Agency (PMDA) and the European Medicines
      Agency (EMA) have provided a wide range of regulatory and scientific consultation
      menus to cover any development stage of drugs and regenerative medicine products,
      respectively. The current study compares Consultations by PMDA and Scientific
      Advice by EMA in terms of consultation types, consultation performances, and
      specific consultation procedures with timelines. Each agency sets intensive but
      highly professional procedures and timelines in order to provide sufficient
      advice in a timely manner. Both agencies complete the consultation process for
      approximately 3 months while an application is reviewed by experts and close
      communication with the applicant is provided. Although PMDA and EMA have some
      differences of approaches to provide well-considered scientific opinions as
      quickly as possible, both agencies have made efforts to support the development
      of better products for patients. Sharing technical insights through consultation
      experiences will contribute to earlier access of patents to new products in both
      Japan and the EU.

PMID- 30231708
TI  - Empirical Study on Job Satisfaction of Clinical Research Associates in China.
AB  - BACKGROUNDS: The level of job satisfaction among clinical research associates
      (CRAs) is of importance because it may affect CRAs' retention, turnover, and then
      further affect the quality of clinical trials. OBJECTIVES: The objectives of this
      study were to (1) examine the level of job satisfaction among CRAs in China and
      (2) explore the association between CRAs' demographic and work-related
      characteristics and their job satisfaction. METHODS: A Chinese CRA job
      satisfaction questionnaire was developed to measure CRAs' attitudes in relation
      to their job. The questionnaire contained 6 subcomponents, including work
      content, work reward, supervisors, coworkers, investigators, and organization
      administration. Then an anonymous cross-sectional web-based survey was conducted
      among CRAs in China. RESULTS: 465 valid questionnaires were received (93%
      response rate). The overall job satisfaction of Chinese CRAs was moderate. As for
      the individual subcomponents, coworkers ranked the highest and work reward ranked
      the lowest. The female group was more satisfied with investigators than were the
      male group. Different scores with supervisors were seen among age groups.
      Different scores with overall satisfaction, work reward, and organizational
      administration were seen among geographic location groups and also among company
      type groups. There were no significant differences in job satisfaction based on
      marital status, education level, and working position of the respondents.
      CONCLUSIONS: Chinese CRAs were moderately satisfied with their job. They were
      most satisfied with coworkers and most dissatisfied with work reward. Further,
      Chinese CRAs' job satisfaction levels were more related with work-related
      characteristics, including geographic location and company type.

PMID- 30231709
TI  - Risk of Acute Asthma Attacks Associated With Nonsteroidal Anti-inflammatory
      Drugs: A Self-Controlled Case Series.
AB  - BACKGROUND: Although asthma attacks are known adverse events associated with
      nonsteroidal anti-inflammatory drug (NSAID) use, few studies have quantified
      these risks. The objectives of this study were to utilize an epidemiological
      approach to quantitatively evaluate the risk of acute asthma attacks associated
      with NSAID prescription in Japan and to compare the risks among NSAIDs according
      to their cyclooxygenase (COX)-2 selectivity. METHODS: We conducted a self
      controlled case series study using Japanese health insurance claims data. Exposed
      cases were identified as those who had experienced both NSAID prescription and
      acute asthma attack, which was defined as the combination of an inhalation
      procedure and the prescription of any inhaled beta2-agonist. The incidence rate
      ratios (IRRs) and 95% confidence intervals (CIs) for NSAID prescription periods
      compared with baseline periods were calculated using conditional Poisson
      regression models; COX-2 selective and nonselective NSAIDs were similarly
      compared. RESULTS: We identified 9769 subjects, more than 95% of whom were
      younger than 60 years. There was a significantly higher risk of acute asthma
      attacks during the NSAID prescription period when compared with the baseline
      period. The quantified IRRs were, in descending order, 93.94 (95% CI, 90.10
      97.95) for the prescription start date, 3.96 (95% CI, 3.63-4.33) for 1 to 9 days
      after the prescription start date, 3.01 (95% CI, 2.78-3.25) for 7 days after the
      prescription end date, 2.19 (95% CI, 1.82-2.65) for >9 days after the
      prescription start date, and 1.44 (95% CI, 1.29 -1.61) for 7 days before the
      prescription start date. There were lower asthmatic risks for COX-2 selective
      NSAIDs compared with nonselective NSAIDs. CONCLUSIONS: The use of NSAIDs in Japan
      was associated with an increased risk of acute asthma attacks. However, this risk
      was lower in COX-2 selective NSAIDs.

PMID- 30231710
TI  - The Company Core Data Sheet in Light of XML-Authoring and IDMP Master Data
      Implementation.
AB  - Labeling decisions for core labeling and/or local labeling capture the outcome of
      all discussions on the product statements that are necessary to ensure safe and
      effective handling of pharmaceutical products, with a special focus on the
      decision concerning known, suspected, or hypothetical risks. Such decisions may
      determine if a topic is to be included in the label or provide a rationale for
      exclusion from the label. The need to provide special advice to users and the
      type of advice (eg, contraindications, precautions) are subject to labeling
      decisions as well. While the problem is well known to pharmaceutical companies,
      and technical solutions such as XML-based authoring/coding systems try to offer
      support from the information technology sector to handle the business problem,
      the current identification of medicinal products (IDMP) requirements raised by
      health authorities worldwide have put a new focus on the problem. This article
      will elaborate on the basic business problem and its requirements with respect to
      a solution.

PMID- 30231711
TI  - Structured Risk Assessment for First-in-Human Studies.
AB  - We describe a structured risk assessment and risk mitigation process that is
      currently used to evaluate proposed first-in human (FiH) studies. This process
      balances the inherent risks of an FiH study with maximal protection of subjects.
      Risk assessment should consider all available data, carefully identifying aspects
      that may lead to risk for healthy subjects. A structured risk assessment avoids
      omissions and promotes consistency. Such a risk assessment should be performed
      for Investigational Products as well as for challenge agents and study
      procedures. Careful risk assessment recognizes gaps of knowledge and emphasizes
      that FiH studies are tolerability, not toxicity, studies.

PMID- 30231712
TI  - Clinically Meaningful Outcomes in Early Alzheimer Disease: A Consortia-Driven
      Approach to Identifying What Matters to Patients.
AB  - BACKGROUND: Numerous statistically derived composite measures have recently been
      proposed as clinical outcome assessments (COAs) for clinical trials in the early
      stages of Alzheimer disease. Critical Path Institute's Coalition Against Major
      Diseases (CAMD) advanced a proposed statistically derived composite measure to
      regulatory agencies with the goal of qualifying it as a COA for pre-dementia
      trials. In response to FDA's requirement to demonstrate that proposed COAs are
      meaningful to patients, this project aimed to identify the most important
      cognition-related concerns patients and informants report early in the disease
      and determine how this information maps to what is assessed by several
      statistically derived composite measures. METHODS: Leveraging qualitative
      research completed by Critical Path Institute's Patient-Reported Outcome
      Consortium, CAMD utilized a summary report that included frequency grids of
      reported concerns of amnestic mild cognitive impairment patients and their
      informants, as well as the narrative transcripts from focus groups. Transcripts
      were reviewed and analyzed to identify which cognitive domains the patient- and
      informant-reported concerns mapped onto. The results were then compared to see
      how well these cognitive domains were represented in various statistically
      derived composite measures. RESULTS: The patient- and informant-reported concerns
      primarily mapped to the cognitive domains of episodic memory and, secondarily,
      orientation and language. Depending on the specified composite, there were
      varying levels of alignment between their subcomponents and these cognitive
      domains. CONCLUSION: Through secondary analyses of existing qualitative data,
      this study examined several statistically derived composite measures and found
      that they generally capture cognitive domains that reflect aspects of day-to-day
      functioning that patients and informants consider meaningful.

PMID- 30231713
TI  - An Analysis of Japanese Patients Enrolled in Multiregional Clinical Trials in
      Oncology.
AB  - The Japanese regulatory agency, the Ministry of Health, Labour and Welfare,
      requires sponsors to enroll a specific number or proportion of Japanese patients
      in multiregional clinical trials (MRCTs) in order to allow for the appropriate
      statistical evaluation of the efficacy and safety of an investigational drug in
      the Japanese population. This means the actual proportion of Japanese patients to
      the total sample size would need to be determined by taking into account the
      proportion of patients in other regions as well as the appropriate statistical
      considerations. Determining the proportion of Japanese patients that satisfies
      the regulatory agency's statistical requirement, along with taking into account
      the practical limitations of patient enrollment, would be difficult for sponsors.
      We believe that recent studies about the proportion of Japanese patients enrolled
      in MRCTs provides sponsors with useful information about partitioning sample size
      into individual regions for MRCTs in oncology. In this study, we investigated the
      proportion of Japanese patients in MRCTs and further compared the efficacy
      results from the overall population to that of the Japanese population. The
      proportion of Japanese patients averaged approximately 10.9%, but the proportion
      varied depending on the drug type. The results of the primary endpoints in
      Japanese patients were similar to those of the overall population, regardless of
      the proportion of Japanese patients.

PMID- 30231714
TI  - Goods and Services Tax on Pharmaceuticals in Malaysia.
AB  - In Malaysia, the goods and services tax (GST) was implemented in 2015. Within
      this context, medicines are subjected to GST. However, essential medicines are
      exempted. In fact, exempting essential medicines from tax is in line with the
      Malaysian National Medicines Policy which aims to promote equitable access to
      affordable essential medicines of good quality to improve health outcomes of the
      people. The implementation of GST on medicines can generate a stable source of
      revenue for the nation. However, there are some ways/actions that could be
      considered to ensure the affordability and accessibility of all medicines post
      implementation of GST in Malaysia.

PMID- 30231715
TI  - Accelerated Access to Medicines: An Ethical Analysis.
AB  - In recent years, a range of initiatives have been introduced to provide patients
      with access to medicines outside of traditional regulatory and/or funding
      channels; we term these processes "accelerated access to medicines." These
      generally take 1 of 3 forms: those that provide access by making existing
      regulatory and funding processes more efficient, those that provide access
      despite uncertainties surrounding safety or efficacy, and those that provide
      access despite uncertainties surrounding cost-effectiveness. These latter 2 types
      are the subject of intense debate, as they generally require us to suspend or
      override accepted standards of evidence of safety, effectiveness, and/or cost
      effectiveness. Ethical analysis provides valuable insights into these debates and
      highlights the risks and benefits that may accrue as a consequence of different
      accelerated access schemes. In this article, we use the principle-based approach
      to ethical analysis described by Beauchamp and Childress (sometimes called the
      "four principles approach" because it frames analysis by reference to
      beneficence, non-maleficence, autonomy, and justice) to analyze initiatives that
      provide accelerated access to medicines. We identify a number of ethical issues
      that may arise in the context of accelerated access initiatives, including
      potential patient harms, impacts on patient autonomy and informed consent, and
      effects on research and regulatory systems. The complex ethical issues at play
      emphasize that there is no single answer to questions as to whether such schemes
      are "ethical"; rather, ethical principles will need balancing, context will be
      critically important, and discussion among the various stakeholder groups will be
      needed to reach an "ethically good" outcome.

PMID- 30231716
TI  - Preapproval Access and Right-to-Try Initiatives: What Are We Willing to Give Up?
AB  - There is a growing concern within the US Food and Drug Administration (FDA) and
      the pharmaceutical/biotechnology communities about state-based initiatives to
      provide access to drugs that are in the early stages of development. These
      legislative bills allow a patient to circumvent the protections afforded by
      regulated procedures as embodied in FDA regulation and guidance. Over the course
      of more than 80 years, the latter have served to best ensure the safety and
      therapeutic efficacy of new medicines and have evolved into an effective set of
      protections of human privacy, dignity, and fairness. To undermine these
      longstanding principles may have consequences which we, as society, must be
      prepared to address. This article examines the dynamic tensions that exist
      between the perceived best interests of the individual patient, the patient
      community, legislators, regulators, physicians, and the society at large.
      Decisions have consequences and, too often, these fail to be considered in the
      process of choosing the pathway that, in a context fraught with uncertainty, best
      meets a desperate need.

PMID- 30231717
TI  - Challenges With the Development of Biosimilars in Asia for Western Markets: An
      Overview and Suggested Solutions.
AB  - There is a great interest from companies located in Asia to bring biosimilars
      into Western markets such as the United States, European Union, and Canada,
      because these are lucrative markets with patents expiring or close to expiry for
      many originator biologics. Although many sponsors are successfully developing and
      marketing biosimilars for their own countries, there is an increasing interest
      among companies in China, Hong Kong, India, Korea, Taiwan, and other Asian
      countries in targeting markets in the West. As a result, there is widespread
      interest among these companies in learning about the requirements for regulatory
      approval in Western countries. This paper, specifically prepared for this
      journal's wide readership, presents an overview of common challenges identified
      while working on global biosimilar programs for companies in Asia targeting
      registration in the West, and also proffers some suggested solutions.

PMID- 30231718
TI  - Characteristics That May Help in the Identification of Potentially Confusing
      Proprietary Drug Names.
AB  - PURPOSE: This study aimed to provide a descriptive analysis of characteristics
      that are common among drug name pairs involved in name confusion medication
      errors. METHODS: We evaluated drug name pairs that contained at least one
      proprietary name from the Institute for Safe Medication Practices (ISMP) List of
      Confused Drug Names. For each name pair, we analyzed whether the following
      characteristics were present: (1) the same first letter, (2) a shared letter
      string of at least 3 letters, and (3) similarity in the number of letters.
      Additionally, we obtained the combined Phonetic and Orthographic Computer
      Analysis (POCA) score. RESULTS: Ninety-nine percent of the drug name pairs
      reflected at least one of the 3 characteristics analyzed. Additionally, 75% of
      the names had a combined POCA score of >=50%. CONCLUSIONS: This descriptive
      analysis provides some insight into characteristics that may be associated with
      name confusion, which should be considered when formulating and evaluating
      proposed proprietary drug names.

PMID- 30231719
TI  - Innovation for Safe and Effective Medical Devices: Contributions From Postmarket
      Surveillance.
AB  - BACKGROUND: Recent years have seen great interest in finding new ways to develop
      innovative, safe, and effective medical devices. While there has been
      considerable research on the lead user and open innovation approach, relatively
      little attention has been given to postmarket surveillance as a valuable source
      of safety-related information on medical devices. METHODS: An online
      questionnaire was sent to 118 postmarket surveillance experts throughout Germany
      to find out (1) what instruments medical device manufactures use to promote an
      internal transfer of postmarket surveillance knowledge and (2) to what extent
      this can lead to impulses for research and development meant to improve or
      develop new medical devices. RESULTS: Our results showed that technical and human
      resource-related instruments are of particularly high importance for the
      intraorganizational transfer of postmarket knowledge. CONCLUSIONS: The transfer
      of this postmarket-related device knowledge can have a positive impact on the
      improvement or development of (especially incremental) medical device
      innovations, thus contributing to a company's success and strengthening device
      related patient safety at the same time.

PMID- 30231720
TI  - Assessing the Quality of Decision Making in the Development and Regulatory Review
      of Medicines: Identifying Biases and Best Practices.
AB  - BACKGROUND: Although the quality of decision making (QDM) in the development and
      regulatory review of medicines influences the delivery of new products, there
      appears to be no suitable instrument to assess QDM in this area. The aim of this
      study was to assess differences in QDM using a validated instrument, the Quality
      of Decision-Making Orientation Scheme (QoDoS), to identify best practices and
      biases affecting individuals and their organization, as well as to assess
      differences in decision-making behaviors between pharmaceutical companies and
      regulatory agencies. QoDoS also enables the measurement against 10 quality
      decision-making practices (QDMPs) that underpin a quality process. METHODS:
      QoDoS, consisting of 47 items that assess individual and organizational decision
      making approaches and influences, was completed by 76 participants from
      regulatory agencies and pharmaceutical companies. RESULTS: Having a systematic,
      structured approach to aid in decision making is achieved to a greater extent at
      an individual level (72%) compared with that of the organization (38%). Key
      differences between company and agency decision making were uncovered. While it
      was recognized that both stakeholders felt that their decision making could be
      improved (100% agencies; 92% companies), training in the science of decision
      making was rarely provided. CONCLUSIONS: QoDoS has the ability to measure
      differences in QDM between individuals and organizations within companies and
      agencies. The benefits of assessing QDMPs with QoDoS include enabling an
      increased awareness of biases and best practices that should be incorporated into
      a decision-making framework; increasing productivity and reducing uncertainty
      around decision making, thereby resulting in more predictable outcomes for
      organizations. In addition, it provides a basis for discussion of the issues in
      decision making within an organization as well as between stakeholders to
      encourage a level of partnership. Finally, measurements of QDM will enable trust,
      consistency, transparency, and timeliness to be built into critical decisions
      that affect medicines' availability.

PMID- 30231722
TI  - Introduction to the "Right to Try" Special Section.

PMID- 30231721
TI  - Accelerated Pathways Work-Now What? A Survey of Payers in the United States.
AB  - BACKGROUND: The US FDA has developed numerous accelerated pathways (APs) to
      facilitate faster development and approval of innovative drugs addressing unmet
      needs. METHODS: To gauge how payers in the United States view APs, PAREXEL and
      the Network for Excellence in Healthcare Innovation (NEHI) surveyed 20 national,
      regional, public, and private payers whose coverage decisions impact 228 million
      patients. RESULTS: The survey shows that APs have created new challenges and
      concerns for payers, including greater difficulty valuing drugs that have less
      clinical information available at launch. CONCLUSIONS: Our survey indicates that
      policies must further the goal of getting needed new medicines to patients
      expeditiously, while managing the risks AP drugs entail for payers and, most
      importantly, patients. For developers, a trend toward value-based assessments of
      both AP and non-AP drugs by payers may require ever-earlier and more data-driven
      decision making about the value of new products in development.

PMID- 30231723
TI  - Reconciling States' "Right to Try" Legislation and FDA's Expanded Access Program:
      Legal Issues.
AB  - In the past few years, a number of states have passed "Right to Try" (RTT) laws.
      These laws aim to facilitate access by terminally ill patients to potentially
      lifesaving investigational products (most commonly drugs) that are not approved
      for the market but have passed phase I of the Food and Drug Administration's
      (FDA's) clinical trial process and continue to undergo testing in clinical
      trials. Two other conventional ways for patients to access potentially life
      prolonging investigational drugs are through a clinical trial (if the patient
      meets enrollment criteria) or through the FDA's expanded access program. This
      article discusses legal issues relating to the role of state and federal
      governments in expanded access to investigational drugs.

PMID- 30231724
TI  - Patient Voice in Rare Disease Drug Development and Endpoints.
AB  - While planning for a successful clinical trial in a prevalent condition is no
      trivial orchestration, even more complicated is the coordination of novel,
      delicate and critical operational components necessary for the successful conduct
      of clinical trials of rare disease (RD). We highlight some of the inherent and
      practical challenges to conducting clinical trials and selecting or developing
      endpoints for RD and the importance of including the patient voice or
      perspective. These challenges include the lack of regulatory precedent for
      proposed endpoints, a void of available measures, little or no published
      literature or natural history information, the practicalities of obtaining access
      to patients, and the appropriateness of placebo-controlled trials. As part of our
      review, we include practical considerations for addressing these issues along
      with a regulatory perspective regarding potential logistic and methodologic
      challenges. We conclude that the patient perspective is a critical component in
      defining treatment benefit and in interpreting the meaningfulness of a change (or
      lack thereof). Engaging with patients is needed at multiple steps along the long
      road of drug discovery.

PMID- 30231726
TI  - Transitions, Introductions, and a Notable Announcement From the US FDA in
      December 2016.

PMID- 30231725
TI  - A Global Perspective on Compassionate Use and Expanded Access.
AB  - Whilst the complex ethical and benefit/risk questions that need to be considered
      when determining whether an investigational treatment should be given to a
      patient remain constant throughout the world, the practical and logistical
      realities of running an Early Access Program (EAP) differ widely globally
      presenting a whole range of challenges if the objective is to find solutions that
      are in the patients best interest and are as fair and equitable as possible. Some
      of the complexities can create extreme challenges for Pharma Companies looking to
      set up global programs, but with the right planning and strategy it is possible
      to overcome hurdles allowing patients to access critical treatments they
      desperately need. The exact design and scope of any global EAP will depend on
      country scope, expected demand, regulatory feasibility, the license status of the
      product, necessary drug pricing structure, as well as company strategy, costs,
      and product supply. Having worked in this space for many years, I am constantly
      reminded of the dramatic positive impact early access to critical treatments can
      have on the lives of patients and their families. I am also well aware of the
      potential risks that need to be well thought through and managed in order to
      provide access in a timely and compliant manner to the right patients and to
      compliment and support, rather than disrupt, traditional development pathways.

PMID- 30231727
TI  - Ethical Considerations in Adaptive Design Clinical Trials.
AB  - Adaptive design clinical trial methodologies offer both opportunities and
      challenges for observing basic ethical principles in human subject research.
      Using both published and unpublished adaptive design clinical trials, we have
      selected and reviewed examples of clinical trials with different design
      adaptations to discuss the ethical obstacles presented and often successfully
      resolved by these approaches, including (1) confirmatory trials for treatments
      widely accepted on the basis of uncontrolled case series or open-label trials
      (clinical equipoise and "justice" in the sense of which trial groups will
      "receive the benefits of research and bear its burdens") (infantile
      hemangioma/propranolol); (2) interim results analysis by unblinded data
      monitoring committees ("withholding information necessary to make a considered
      judgment" ["respect for persons"] versus compromising the trial's scientific
      basis) (BIG 1-98); (3) adaptations involving sample size reassessment or dose
      adjustment via dropping or adding treatment arms, allowing fewer subjects to
      produce statistically significant results, fewer subjects treated with
      ineffective/toxic doses, and more subjects given doses showing tolerance and
      treatment activity ("beneficence" or "protecting from harm and making efforts to
      secure wellbeing") (ECMO, Neuromyelitis Optica); (4) adaptive randomization
      inferential problems balanced against ethical benefits (trastuzumab vs taxane in
      advanced gastric cancer; ADVENT); (5) more efficient allocation of societal
      resources for research, in both public and commercial realms, versus uncertain
      regulatory acceptance (indicaterol; VALOR); and (6) platform, umbrella, and
      basket trials offering additional efficiencies (I-SPY II, BATTLE, Lung-MAP). The
      importance of careful design, meticulous planning, and rigorous ethical review of
      adaptive design trials on a case-by-case basis cannot be overemphasized.

PMID- 30231728
TI  - Who Stands to Benefit? Right to Try Law Provisions and Implications.
AB  - As of late November 2016, 32 states had adopted right to try laws. These laws are
      intended to allow terminally ill patients pre-approval, or "compassionate,"
      access to drugs, devices, or biologics that are in development and have not yet
      been approved by the United States Food and Drug Administration (FDA). While the
      laws' intentions and their impact have been examined, little has been written
      about variations among the state laws. An examination of the specific provisions
      in and differences among the 32 statutes, and who stands to gain from them,
      suggests that the benefits of right to try laws are largely rhetorical. So,
      although the laws have been heralded as pro-patient, they ought to be understood
      as merely masquerading as patient-centric legislation. We call for a re
      examination and amendment or, ideally, repeal of these laws in order to prevent
      the very real risk of patient harm caused by both some of the laws' provisions
      and patients' confusion arising from these misleading statutes.

PMID- 30231729
TI  - A Cross-Sectional Study on the Use of, Preference for, and Perceived Reliability
      of Mass Media for Drug-Related Information Among the General Public in Sarawak.
AB  - BACKGROUND: Because of the large size of Sarawak and the high proportion of
      people residing in rural areas in this Malaysian state, disseminating drug
      related information there can be challenging. It is, therefore, important to
      recognize the type of mass media for drug-related information that are salient to
      the people of Sarawak. This study was aimed at identifying the use of and the
      preferences for mass media to obtain drug-related information among the public in
      Sarawak. We also aimed to recognize the media perceived as the most reliable for
      drug-related information. METHODS: This was a cross-sectional study using a self
      administered questionnaire carried out from September to October 2013. Survey
      respondents were recruited from 4 divisions in Sarawak: Kuching, Sibu, Miri, and
      Bintulu. RESULTS: A total of 433 completed questionnaires were obtained at the
      end of the study period. All respondents had access to common mass media such as
      television (89.8%, 389/433), radio (68.6%, 297/433), and the Internet (66.1%,
      286/433). Among all respondents, television (71.4%, 309/433) was noted as the
      most preferred media for drug-related information. Compared with rural
      respondents, urban respondents were significantly more likely to have access to
      and prefer the Internet to obtain drug-related information. On the other hand,
      rural respondents were more likely to have access to and prefer radio for such
      information compared to their urban counterparts. CONCLUSIONS: Television can be
      an important and attractive choice of mass media in a quality use of medicines
      (QUM) campaign. The Internet can be used to disseminate drug-related information
      in urban areas, whereas radio can be used in a QUM campaign targeting the rural
      public.

PMID- 30231730
TI  - Sample Size Calculations for Combination Drugs of 2 Monotherapies With a Single
      Approved Dose Level: Binary Endpoint Cases.
AB  - BACKGROUND: In this article, we study the sample size calculations for the
      combination drugs of 2 monotherapies with a single approved dose level when the
      primary endpoints are binary. METHODS: Two study cases are examined: In the
      first, each monotherapy has the same indication, while in the second, each
      monotherapy has a different indication. The sample sizes are calculated by using
      an asymptotic joint distribution of test statistics and employing unequal
      allocation for 3 popular measures of 2 proportions: the risk difference, the log
      relative risk, and the log odds ratio. RESULTS: Results show that our proposed
      method produces smaller total sample sizes compared with the heuristic method.
      CONCLUSIONS: The total sample sizes can be reduced by incorporating unequal
      allocation and dependency between 2 test statistics.

PMID- 30231731
TI  - A Bayesian Exposure-Time Method for Clinical Trial Safety Monitoring With Blinded
      Data.
AB  - The FDA safety reporting Final Rule requires an expedited safety report whenever
      aggregate analysis indicates a clinically meaningful imbalance with an adverse
      event occurring more frequently in the drug treatment group than in a concurrent
      or historic control group. We introduce a safety monitoring procedure for two-arm
      blinded clinical trials that can be used to help address new requirements from
      the recent FDA safety reporting Final Rule. This procedure incorporates a
      Bayesian hierarchical exposure-time model for using prior information and blinded
      event data to make inferences on the rate of adverse events of special interest
      in the test treatment arm. We describe a collaborative process and provide free
      software for eliciting the required prior information and calibrating operating
      characteristics through simulation. We illustrate the use of our procedure with a
      case study composed of a combination of real and simulated data. Our procedure
      provides good operating characteristics for detecting higher than expected rates
      of adverse events in the drug treatment group, and is appropriate for inferring
      the rate of adverse events in multi-armed clinical trials with blinded data.

PMID- 30231732
TI  - Comparison of Drug Use Between Clinical Practice and Regulatory Approval: Results
      in Older Japanese Patients With Rheumatoid Arthritis, Diabetes, High Blood
      Pressure, or Depression.
AB  - BACKGROUND: In this study, differences in older patients between drug use as
      reported in clinical practice and in clinical trials for regulatory approval were
      examined. METHODS: Electronic medical record (EMR) data such as patient
      background (age, sex), concomitant drugs, data on laboratory tests, and
      prescribed doses of drugs from outpatients with rheumatoid arthritis, diabetes,
      high blood pressure, or depression at Chiba University Hospital were obtained for
      the period from January 2003 to December 2012. These data were compared with data
      from relevant clinical trials for regulatory approval in order to examine
      differences in drug use. RESULTS: There were 5134 eligible patients. The
      prescribed doses of drugs were lower than the standard approved doses for
      depression and rheumatoid arthritis but were generally within the approved dose
      range for type 2 diabetes mellitus and hypertension. When comparing the
      characteristics of older patients taking tacrolimus, 5.6% to 17.0% of those would
      not be able to participate in clinical trials because of liver or renal
      abnormality, and the incidence rates of some adverse drug events (ADEs) differed
      significantly between clinical practice and clinical trials. CONCLUSIONS:
      Appropriate doses of drugs for older patients may differ from approved doses in
      certain diseases. Complex situations such as a lot of polypharmacy, comorbidity,
      and functional impairment in older patients in clinical practice make it
      difficult to evaluate safety based on data from clinical trials. In the future,
      utilization of a database created from the EMR of older patients should be
      considered for assessment of drug safety in older patients in clinical practice.

PMID- 30231733
TI  - The PharmD/MD Dual-Degree Program and Its Potential Value in the Pharmaceutical
      Industry.
AB  - The first dual-degree program combining both the doctor of pharmacy (PharmD) and
      the doctor of medicine (MD) degrees was designed and launched by Rutgers, The
      State University of New Jersey, in academic year 2013-2014. This joint effort was
      led by the Ernest Mario School of Pharmacy (EMSOP) and the Robert Wood Johnson
      Medical School (RWJMS) to combine expertise in both diagnostic and treatment
      facets of health care and to prepare graduates for leadership roles in providing
      and managing comprehensive patient care in a variety of settings. One area of
      potential value of these skill sets is the drug development industry. A survey
      was conducted among pharmaceutical executive stakeholders associated with a
      postdoctoral training program to assess the perceived value of this new dual
      degree skill set and to identify particular functions where the combined training
      has its best fit. Results indicate that the combined nature of this training is
      highly valued in this setting, especially in the areas of clinical pharmacology,
      drug safety and pharmacovigilance, medical affairs/strategy, and medical science
      liaisons. Future monitoring of graduates will further define the value of this
      dual degree in this and other health care settings.

PMID- 30231734
TI  - Evaluating the Effectiveness of Repricing for Market Expansion in the Japanese
      Drug Pricing System.
AB  - BACKGROUND: In 1994, the "Repricing for Market Expansion" system (the repricing
      system) was introduced to the pharmaceutical market in Japan to improve the
      financial performance of the national health insurance system. In 2010, the
      "Reward Premiums for the Promotion of Innovative Drug Discovery and the
      Resolution of Off-Label Use Issue, Etc." system (the reward system) was
      introduced to promote the development of new drugs. This study evaluates the
      effectiveness of these systems from an empirical perspective. METHOD: The data
      set used in this study was created using publicly available information from the
      Ministry of Health, Labour and Welfare (MHLW) website and a market database
      maintained by IMS Japan Pharmaceutical Market Sales. RESULTS: Anticancer or
      immunomodulating drugs were the most frequently affected by the repricing system.
      The sales of similar drugs did not exceed double the sales forecast, and to begin
      with, the repricing system was not applied to these drugs, unintentionally
      reducing the profitability of pharmaceutical companies. In addition, we found
      that pharmaceutical expenditures have been steadily and significantly increasing,
      although this aspect is just one of the circumstances surrounding the Japanese
      pharmaceutical market. CONCLUSIONS: On the basis of these results, we propose
      that the current repricing system be replaced with one using a market mechanism
      that can evaluate the value of drugs from an economic perspective and help
      improving the financial performance of the national health insurance system. We
      also suggest that the number of generic medications on the market in Japan be
      increased to a ratio equivalent to those of the US and EU. We hope that the
      perspectives on Japan's unique drug pricing system obtained from this article are
      utilized by pharmaceutical companies in developing their businesses in Japan.

PMID- 30231735
TI  - Public- and Private-Sector Contributions to the Research and Development of the
      Most Transformational Drugs in the Past 25 Years: From Theory to Therapy.
AB  - BACKGROUND: With available funding from the public sector decreasing while
      medical needs and scientific complexity increase, private-sector collaborations
      with academia and government have become increasingly key in furthering medical
      innovation. Nonetheless, some skeptics diminish the contribution of the private
      sector to the discovery and development of truly innovative drugs on the one
      hand, while on the other hand they assert that research and development (R&D) of
      new medicines could and should be exclusively within control (at least
      financially) of the government. This begs the question, How much government
      funding would be needed to replace industry new drug R&D spending? METHODS: We
      address the respective roles of the private and public sectors in drug
      development by examining a diverse array of evidentiary materials on the history
      of 19 individual drugs, 6 drug classes, and 1 drug combination identified as the
      most transformative drugs in health care over the past 25 years by a survey of
      over 200 physicians. RESULTS: Only 4 of the individual drugs appear to have been
      almost completely researched and developed by one sector. One sector or the
      other, however, did dominate particular phases of the R&D continuum. For example,
      54% of basic science milestones were achieved predominantly by the public sector
      and 27% by the private sector. For discovery milestones, it was 15% by the public
      sector and 58% by the private sector. The private sector was also dominant in
      achieving the major milestones for both the production and drug development
      phases (81% and 73% of the drugs reviewed, respectively). For 19% to 27% of the
      case histories for the various categories, dominance of one sector versus the
      other could not be determined. On the question of replacing industry's spending
      on the R&D of medicines, we estimate quite conservatively that the amount that
      would have to be spent by government would be nearly double the budget of the
      National Institutes of Health just to maintain the flow of the most innovative
      drug approvals and would have to increase nearly 2.5 times that level to maintain
      the development of all new drugs. CONCLUSIONS: Our analysis indicates that
      industry's contributions to the R&D of innovative drugs go beyond development and
      marketing and include basic and applied science, discovery technologies, and
      manufacturing protocols, and that without private investment in the applied
      sciences there would be no return on public investment in basic science.

PMID- 30231736
TI  - Current Practice on Multiplicity Adjustment and Sample Size Calculation in Multi
      arm Clinical Trials: An Industry Survey in Japan.
AB  - BACKGROUND: This study provides the results of a survey on the current practice
      of multiplicity adjustment and sample size calculation in multi-arm clinical
      trials. METHODS: The survey was aimed at members of the Japan Pharmaceutical
      Manufacturers Association (JPMA) and was conducted in 2015. RESULTS: Of the 66
      JPMA member companies, effective responses were obtained on 151 trials from 33
      companies based in Japan and 11 companies based in other countries. The results
      from this survey indicate that multiplicity adjustment in confirmatory multi-arm
      trials is adequate in terms of controlling the familywise error rate.
      Multiplicity was adjusted in 38.3% of exploratory multi-arm trials. Various
      multiple comparison procedures (MCPs) were applied, with the fixed sequence
      procedure being the one applied most frequently. This survey also reveals that
      there are issues that need to be addressed within sample size calculation.
      CONCLUSIONS: To adequately design a multi-arm clinical trial, it is important
      within sample size calculation to consider whether to perform multiplicity
      adjustment, select MCPs, and define their power.

PMID- 30231737
TI  - Postmarketing Benefit-Risk Assessment for Erythropoiesis-Stimulating Agents Using
      a Health Care Database.
AB  - BACKGROUND: While benefit-risk (B-R) assessment in the real-world setting is an
      important challenge for pharmacovigilance, few studies have explored this
      approach. To investigate the utility and limitations of B-R assessment using a
      health care database by applying the Benefit Risk Action Team (BRAT) framework,
      we have conducted a case study with erythropoietin agents. METHODS: Postmarketing
      data from the Medical Data Vision health care database were used in a B-R
      comparison between methoxy polyethylene glycol-epoetin beta (continuous
      erythropoietin receptor activator; C.E.R.A.) and other erythropoiesis-stimulating
      agents (ESAs). Data were from patients with chronic kidney disease (CKD) treated
      with C.E.R.A. (n = 131: nondialysis, 109; hemodialysis, 22) or other ESAs (n =
      542: nondialysis, 327; hemodialysis, 215) between July 2011 and March 2014.
      RESULTS: The B-R profile for C.E.R.A. appeared to be similar to that for other
      ESAs in both nondialysis and hemodialysis patients with CKD, when benefits and
      risks were mainly assessed in terms of odds ratios. Despite various point
      estimates and confidence intervals for each outcome, the results of subgroup
      analyses showed no notable differences from the overall analysis in B-R
      assessment. CONCLUSIONS: B-R assessment can be performed using the BRAT framework
      with a health care database, but limitations exist when using a single data
      source. Care should be taken when selecting data for extraction and defining
      outcomes of interest. Further research is necessary to facilitate practical
      application of this approach.

PMID- 30231738
TI  - Pharmaceutical Organizational Size and Phase 3 Clinical Trial Completion Times.
AB  - BACKGROUND: The pharmaceutical industry has continued to experience a large
      number of mergers, often involving the very largest companies. Behind many of
      these mergers has been the desire to achieve scale efficiencies and improved
      performance in both commercial and research and development (R&D) activities.
      METHODS: This research draws upon ClinicalTrials.gov data about commercially
      sponsored phase 3 clinical trials started and completed between 2008 and 2013.
      The research uses the bidirectional stepwise Akaike information criterion for
      model selection, adding a second-order term to the model where second-order terms
      were significant. RESULTS: First, and least surprising, the study therapeutic
      area has a major impact on study completion times. Second, the protocol design
      itself, as well as the clinical study execution plan, can have important
      consequences on study completion times. Several study execution variables are
      also critical to understanding completion times. While the size of clinical trial
      organization is not associated with more rapid completion times, the amount of
      organizational experience that an organization has in a particular therapeutic
      area does have a demonstrable impact. The models are able to supply the specific
      number of incremental completion days associated with each significant variable.
      CONCLUSIONS: Recent years have witnessed increasingly larger pharmaceutical R&D
      organizations, as many companies have worked to achieve the scale benefits of
      organizational size for R&D as well as commercial activity. Larger pharmaceutical
      companies may still achieve scale benefits. Faster phase 3 study completion times
      is not one of them.

PMID- 30231739
TI  - A Toolkit for the Management of Protocol Deviations.
AB  - BACKGROUND: The DIA's Good Clinical Practice and Quality Assurance Community (DIA
      GCP/QA) created a working group to develop templates for a protocol deviation
      standard operating procedure (SOP) and protocol deviation handling plan (PDHP).
      METHODS: The working group consisted of QA auditors, data managers,
      statisticians, and clinical monitors from several pharmaceutical companies,
      academia, and independent auditing firms. Various examples of standard operating
      procedures, data handling plans, and auditing plans were examined, and the core
      elements extracted into the initial PD SOP and PDHP templates. The draft
      templates were presented at a workshop at the DIA 51st Annual Meeting held in
      June 2015 in Washington, DC, and feedback was incorporated. The workshop came at
      the heels of a previously published position paper, "The Lifecycle and Management
      of Protocol Deviations." RESULTS: The PD SOP and the PDHP templates are presented
      in this article. They are a starting point, and each company will need to modify
      to suit its individual needs. CONCLUSIONS: This article expands on the position
      paper to include concrete tools for the management of protocol deviations,
      including best practices for detection, classification, mitigation, and
      management of protocol deviations with a goal to reduce the impact on subject
      safety and data integrity.

PMID- 30231741
TI  - Glory Enough for All.

PMID- 30231740
TI  - An Analysis of Regulatory Timing and Outcomes for New Drug Applications Submitted
      to Swissmedic: Comparison With the US Food and Drug Administration and the
      European Medicines Agency.
AB  - BACKGROUND: This study compared the timing, regulatory marketing authorization
      decisions, and the final labeling for products submitted to Swissmedic to those
      submitted to European Medicines Agency (EMA) and the US Food & Drug
      Administration (FDA). METHODS: The Centre for Innovation in Regulatory Science
      (CIRS) conducted an analysis of a representative cohort of 63 new molecular
      entities (NMEs) that were submitted to Swissmedic from 2006 through 2010 and that
      were also submitted to, and approved by, the EMA centralized procedure and FDA.
      Parameters considered included the outcome and timing of regulatory marketing
      authorization decisions and the comparison of each product's Summary of Product
      Characteristics (SPC) from the 3 agencies. The results were presented at the
      Swissmedic 10th Anniversary Symposium, "The Challenges of Regulation and Changing
      Regulations Paradigms," and they form the basis of this article. RESULTS: The
      median approval times for these NMEs were longer for Swissmedic (480 days)
      compared with FDA (303 days) and EMA (416 days). However, if an expedited
      application review procedure (a "priority review" [FDA], "accelerated assessment"
      [EMA], or "accelerated review" [Swissmedic]) was applied, Swissmedic was faster
      (207 days) than EMA (300 days) and essentially as fast as FDA (229 days). The
      main differences were in the nature of the wording of parts of the initial SPC,
      particularly the "Contraindications" and "Special warnings and precautions" for
      FDA and "Special warnings and precautions" for EMA. CONCLUSIONS: Results suggest
      there is no clear evidence that Swissmedic was substantially different in its
      initial regulatory decisions or SPC recommendations compared with the EMA or FDA.

PMID- 30231742
TI  - Can Registration Procedures of Pharmaceuticals Inadvertently Contribute to Off
      Label Prescribing in Children?
AB  - BACKGROUND: In Malta, off-label prescribing of medicines in children stands at
      45%, mainly because of failure by prescribers to follow the dosing
      recommendations in the product literature. In addition, registration procedures
      of pharmaceuticals may inadvertently contribute to this high incidence of off
      label prescribing. METHODS: A literature review was conducted to identify
      regulatory provisions relating to the registration of medicines in Malta that
      could give rise to off-label use. Furthermore, the product literature of the 2
      classes of medicines most commonly prescribed in children, antibiotics and
      respiratory medicines, were reviewed. This was done in order to gauge whether the
      different registration routes implemented in Malta to market these medicines
      could give rise to off-label use. RESULTS: The national registration procedure
      relating to Article 126a of Directive 2001/83/EC and, to a lesser extent, line
      extensions, parallel importation, and the provision detailed in Article 11 of
      Directive 2001/83/EC were found to lead to discrepancies and potentially
      misleading inclusions in the product literature. These, in turn, may well
      contribute to off-label use of medicines in children. CONCLUSIONS: Off-label
      prescribing does not necessarily mean that efficacy and safety data are
      unavailable. Variances in the product literature of medicines having the same
      active ingredients but imported from different countries may cause divergent
      prescribing practices, leading to inadvertent off-label use. The various
      stakeholders, including member states such as Malta, should devise strategies to
      harmonize the most recent labeling information in order to support the safe and
      effective use of pediatric medicines, thereby decreasing off-label use.

PMID- 30231743
TI  - Implementation of Structured Benefit-Risk Assessments in Marketing Authorization
      Applications: Lessons Learned.
AB  - BACKGROUND: A recent publication from Eli Lilly and Company provided guidance on
      incorporation of a structured benefit-risk assessment framework into Section
      2.5.6 of the Clinical Overview of marketing authorization applications. Because a
      template alone cannot deliver a judicious benefit-risk evaluation, the purpose of
      this manuscript is to present lessons learned and practical approaches that
      pharmaceutical companies (sponsors) can apply in developing holistic benefit risk
      assessments of medicinal products for their marketing authorization applications.
      METHODS: Benefit-risk scientists at Eli Lilly and Company facilitated use of a
      structured benefit-risk assessment in Section 2.5.6 of the Clinical Overview for
      a number of marketing authorization applications submitted to regulators between
      2013 and the 2016. Based on our experiences in implementing the approach
      described in the publication by Wolka et al, we have identified commonalities
      that contributed to successful implementation. RESULTS: The 3 key learnings from
      the authors' experience are to (1) use a cross-functional team approach; (2)
      employ a process that lends to the objectivity and efficiency of benefit-risk
      assessments; and (3) leverage data visualizations for clear and concise
      communication of benefit-risk information. CONCLUSIONS: Sponsors can apply these
      approaches to incorporate benefit-risk assessments into their marketing
      authorization applications. Further shared learnings and benchmarking among the
      pharmaceutical industry will be necessary to further advance the science and
      practice of benefit-risk assessment.

PMID- 30231744
TI  - An FDA Analysis of Formal Dispute Resolution in the Center for Drug Evaluation
      and Research: 2003 Through 2014.
AB  - Scientific and/or medical disputes will inevitably arise with regard to the US
      Food and Drug Administration's (FDA's) decision making related to drug
      development, new drug review, generic drug review, and postmarketing oversight.
      As these disputes can involve complex judgments and issues that are
      scientifically and commercially important, it is critical that FDA have
      procedures for effective and efficient resolution. FDA regulations allow a
      sponsor to obtain a review of an FDA decision by submitting a request for formal
      dispute resolution (an appeal). FDA's Center for Drug Evaluation and Research
      (CDER) received 137 appeal issues for fiscal years 2003 through 2014. However,
      sponsors can appeal the same issue multiple times, and each is considered a
      unique appeal; CDER received and analyzed 173 of these unique appeals. Of these
      173 unique appeals, CDER accepted 140 (81%) for review and refused to accept for
      review 25 (14%). Eight (5%) were withdrawn by the sponsor prior to CDER making a
      decision whether to accept the appeal for review. Of the 140 unique appeals
      accepted and reviewed, CDER granted 23 (16%) appeals and denied 117 (84%). The
      analysis also examines an array of aspects of the process, such as (1) reasons
      why CDER rejected appeals, (2) reasons why sponsors submitted appeals, (3) the
      types of appeals that sponsors submitted, (4) the characteristics of the sponsors
      that submitted appeals (eg, size, past regulatory experience, legal
      representation), and (5) CDER's performance in meeting user fee goals associated
      with dispute resolution.

PMID- 30231745
TI  - Drug Target Identification and Validation: Global Pharmaceutical Industry Experts
      on Challenges, Best Strategies, Innovative Precompetitive Collaboration Concepts,
      and Future Areas of Industry Precompetitive Research and Development.
AB  - Focused interviews were conducted with global pharmaceutical company
      representatives in order to derive a consistent view on drug target
      identification/validation challenges, collaborative strategies, and future
      developments in a precompetitive space. Analysis revealed translation into
      clinical utility as a major hurdle of novel drug target validation, originating
      from lack of biological understanding, irreproducibility of published results,
      and lack of valid animal models. Direct and close collaborations with academia
      are the preferred model to tackle basic research on novel drug targets in high
      risk projects. Efforts to conduct target identification in large precompetitive
      consortia are acknowledged with some doubts about the pace of progress and data
      sharing policies, while concept to extend the precompetitive space to target
      validation in phase II trials was curtailed to niche indications together with a
      revision of current intellectual property (IP) practice. Public-private
      partnerships in established areas are forecasted to increase. Novel emerging
      themes are toxicology data sharing, joint genetic patient data analysis, and
      reimbursement concepts.

PMID- 30231746
TI  - Prospects for Harmonizing Regulatory Science Programs in Europe, Japan, and the
      United States to Advance Regenerative Medicine.
AB  - BACKGROUND: Regenerative medicine (RM) is a game-changing technology with the
      potential to repair damaged tissues and organs, but its introduction into the
      clinic is complicated by the fact that Europe, Japan, and the United States are
      struggling to make appropriate regulatory decisions about advanced technologies
      that are highly promising but also uncertain and potentially risky. They have
      adopted the new approach of regulatory science (RS), applying science-based
      approaches and standards to support regulatory decision making, to address the
      challenge. METHODS: Is RS the right approach for harmonizing the regulatory
      mechanisms needed to integrate RM into the mainstream of the development
      continuum for medical products? If so, what are the prospects for harmonization?
      We examine the current state of the art for RM and RS in the 3 major drug
      development regions to answer these questions. RESULTS: Among the practical
      obstacles to harmonization is the fact that the 3 regions represent different
      legal jurisdictions and health care systems, with disparate regulatory and
      reimbursement requirements. However, the regulatory regimes are not without
      commonalities. Thus, it is not the practical differences that should be debated
      but rather how best to enhance collaboration. CONCLUSIONS: Just as consistent and
      predictable regulatory support founded on common principles in regulatory science
      provide the confidence and certainty required to bolster investment in
      regenerative medicine, harmonization is essential to building that framework on a
      global scale.

PMID- 30231747
TI  - Adaptive Design Practice at the Center for Devices and Radiological Health
      (CDRH), January 2007 to May 2013.
AB  - Adaptive designs have generated great interest in the clinical trial community as
      a result of their versatility and efficiency. Recently, the Center for Devices
      and Radiological Health (CDRH) at the US Food and Drug Administration (FDA)
      surveyed all adaptive design applications submitted between 2007 and May 2013 for
      regulatory review. In this paper, we discuss the overall results and findings
      that emerged from an in-depth examination of the submissions. We summarize the
      current status of adaptive designs used in medical device studies. We also
      identify some of the lessons learned and common pitfalls that we encountered in
      our review of the designs.

PMID- 30231748
TI  - Novel Gastroretentive Controlled Release Formulations for Once-Daily
      Administration: Assessment of Clinical Feasibility and Formulation Concept for
      Raltegravir.
AB  - BACKGROUND: Raltegravir is an integrase strand transfer inhibitor indicated in
      combination with other anti-retroviral medicinal products for the treatment of
      HIV-1 infection, given twice daily. Although a BCS class II compound, raltegravir
      exhibits low colonic absorption, thus making development of modified release
      formulations challenging. It was hypothesized that a gastroretentive (GR)
      formulation would increase trough (C24 h) concentrations of raltegravir, hence
      being amenable to a once-daily (QD) regimen. METHODS: Iterative prototype GR
      formulations were developed in monolithic, bilayer, and trilayer tablet designs.
      Four phase I studies in healthy subjects were conducted to provide proof of
      formulation concept. RESULTS: Raltegravir C24 h was increased by a GR formulation
      with scintigraphy data supporting gastric retention. Single-dose exposures from a
      trilayer tablet administered in the morning with a high-fat meal resulted in
      acceptable C24 h values. However, C24 h values for evening dosing with a high-fat
      meal did not meet the success criteria for QD administration. Raltegravir C24 h
      and area under the curve (AUC) values after AM dosing with a low-fat meal were
      significantly lower than after dosing with a moderate-fat meal. Skipping,
      delaying, or giving a low-fat, low-calorie lunch after dosing with a high-calorie
      breakfast also resulted in an unacceptable decline in C24 h values. The
      requirements for consistent product performance under varying conditions of diet,
      timing of dosing, and dose were not favorable when given as GR tablets.
      CONCLUSIONS: The findings from these studies offer valuable insights into
      modifying the absorption of candidate drugs with limiting colonic permeability
      and solubility characteristics and the interplay between meal, dose timing, and
      GR formulation performance.

PMID- 30231749
TI  - Optimizing the Use of Electronic Data Sources in Clinical Trials: The Landscape,
      Part 1.
AB  - BACKGROUND: TransCelerate BioPharma has created the eSource Initiative with the
      intent to facilitate the industry's movement toward optimal usage of electronic
      data sources. Although guidance and standards have been in place for some time,
      data collection methods and technology have not been utilized to their fullest
      capability, and transcription between electronic systems continues to be the
      norm. METHODS: The TransCelerate approach for the eSource Initiative is to
      understand the current landscape and highlight factors that are influencing the
      adoption of new technologies. As a preliminary step in this process,
      TransCelerate surveyed member companies regarding eSource usage and barriers.
      RESULTS: Literature review, stakeholder engagement, and the member survey have
      provided insight into the current landscape, which will help TransCelerate to
      develop proposals for best practices for industry utilization of electronic data
      collection tools and methods to benefit all stakeholders. CONCLUSIONS: Based on
      survey results, companies generally have taken steps to leverage current eSource
      technologies and prepare for optimal utilization of electronic data sources. The
      TransCelerate eSource Initiative will continue to evaluate the technology,
      regulatory, standards, and health care landscape to support the goal of improving
      global clinical science and global clinical trial execution. Forthcoming
      publications will focus on technology landscape, future vision, and demonstration
      projects.

PMID- 30231751
TI  - Progress on Behalf of Children.

PMID- 30231750
TI  - "Partner in Prime"? Effects of repeated mobile security priming on attachment
      security and perceived stress in daily life.
AB  - Lacking secure attachment representations is associated with vulnerability to
      mental and physical health problems, perhaps mediated by increased susceptibility
      to stress and impaired emotion regulation. Even though cognitive representations
      of self and others tend to favor confirmation over information, research has
      shown that adult attachment security can be positively influenced. In a
      randomized control trial using a mixed between- and within-subjects design,
      participants (N = 112) were mobile primed with attachment security stimulating
      visualization tasks, over a 7-day period. Self-reported attachment security was
      unchanged; however, reduced attachment avoidance and perceived stress and
      increased resilience and self-compassion scores were obtained up to one week
      after the last prime. Participants who reported less effort and more pleasure in
      carrying out the visualization tasks experienced the highest gains. Results
      highlight the potential of mobile attachment security priming for intervention,
      but also the differential potential of such intervention for people with
      different attachment orientations.

PMID- 30231752
TI  - Nonclinical Safety Considerations for the Development of Pediatric-First Drugs:
      An Industry View.
AB  - This paper provides considerations on approaches to the development of medicines
      initially developed for pediatric use (ie, "pediatric-first" or "pediatric-only"
      drugs). The most common development approach for these types of medicines
      involves a first-in-human (FIH) clinical trial with healthy adult volunteers to
      assess safety and tolerability. This approach generally requires nonclinical
      repeat-dose studies in adult animals; safety pharmacology and in vivo genetic
      toxicology studies in adult animals are also performed for small-molecule drugs.
      Additional studies in juvenile animals may be required prior to clinical trials
      in pediatric patients, on a case-by-case basis. In this paradigm, the starting
      dose for pediatric patients is primarily driven by modeling from the adult
      pharmacokinetic assessment and pharmacology data. A second development approach
      is where the FIH clinical trial is conducted in pediatric patients. This approach
      is generally supported by repeat-dose studies in juvenile animals, with the onset
      of dosing at ages that developmentally correlate to the age of the pediatric
      patients. Safety pharmacology and in vivo genetic toxicology studies are
      generally performed in adult animals for small-molecule drugs. To define a safe
      yet minimally efficacious starting dose for pediatric patients, various
      complementing approaches can be used, including human equivalent dose, minimal
      anticipated biological effect level, and physiologically based pharmacokinetic
      modeling. Case examples for pediatric-first drug candidates show how both drug
      development approaches (ie, entry into human first in adults or directly in
      pediatric populations) are used in the pharmaceutical industry.

PMID- 30231753
TI  - A Theory on the Relativity of Factors Impacting the Utilization of Medical
      Information Services From the Pharmaceutical Industry.
AB  - Health care providers have many options for obtaining answers to their questions
      about pharmaceutical products. These options include drug information curators
      and aggregators such as ePocrates, WebMD, and Wikipedia, as well as professional
      journals. However, drug information obtained directly from a pharmaceutical
      company is arguably the best source of information regarding that company's
      medicine. This is because medical information (MI) professionals from the
      pharmaceutical industry have the product expertise, technical skills, and access
      to relevant information that enable current, evidence-based, and scientifically
      accurate information to be provided. Further, it is reasonable to assume that
      "good" information leads to better patient decisions and therefore better patient
      outcomes. Several factors are implicated in the use of a pharmaceutical company's
      medical information resource. These factors include, but are not limited to,
      awareness of the availability of the resource, ease of access, and trust of the
      information. In this paper, the authors discuss the relevance of these factors
      and propose an integrated relational theory (referred to as the "MI Theory of
      Relativity") to model the utilization and value of a medical information service.

PMID- 30231754
TI  - The Impact of Adaptive Design on Portfolio Optimization.
AB  - BACKGROUND: Pharmaceutical portfolios are optimized by improved allocation of a
      fixed budget into individual trials that leads to an improved value of a
      portfolio. This paper investigates how flexibility of adaptive design contributes
      to portfolio optimization. METHODS: An example portfolio was designed, and
      strategies that did or did not include trials with adaptive designs were
      specified. Operating characteristics of a traditional portfolio were compared to
      that of an adaptive portfolio. Adaptive portfolios offer potential advantages
      over traditional ones. Its flexibility largely increases the number of decision
      points, and as such it allows for a much more frequent reassessment of
      portfolios. Additionally, an adaptive portfolio can correct itself if initial
      decisions were made incorrectly. RESULTS: Despite all these advantages, the
      adaptive portfolio did not outperform the traditional portfolio. The main reason
      is that in this case, adaptive designs allowed for increases in sample size to
      the point where improvements per unit increase were minimal, instead of
      allocating this budget to additional trials. CONCLUSIONS: It is critical to
      minimize missed opportunities to initiate new promising trials, and to increase
      sample size only in regions that promise meaningful improvements in power.

PMID- 30231755
TI  - Patient Engagement at a Tipping Point-The Need for Cultural Change Across
      Patient, Sponsor, and Regulator Stakeholders: Insights From the DIA Conference,
      "Patient Engagement in Benefit Risk Assessment Throughout the Life Cycle of
      Medical Products".
AB  - Benefit-risk assessment is the foundation for decision making throughout the life
      cycle of medical products. Because patients are the beneficiaries of the efficacy
      of medical treatments and also bear their possible risks, their perspectives and
      judgments about value and the relative importance of benefits and risks should be
      at the heart of the medical decision-making process. Patient engagement is now at
      a tipping point; there have been a growing number of patient engagement
      initiatives over the past several years, but there remains the need for a common
      language, alignment on engagement approaches and best practices, and a shared
      vision regarding a desired future state. This article discusses insights gleaned
      from the DIA conference, "Patient Engagement in Benefit-Risk Assessment
      throughout the Life Cycle of Medical Products" (September 2015). It highlights
      the changes that will need to occur within the patient, medical-product sponsor,
      and regulatory cultures in order for patient engagement to become integrated into
      the medical-product development process and life cycle maintenance. Furthermore,
      it emphasizes that reaching the desired future state will require a conscious
      commitment from all stakeholders to work collaboratively to develop shared
      solutions and to map a common path forward.

PMID- 30231756
TI  - Attitudes Toward Clinical Trials Among Physicians in China With Different Levels
      of Experience.
AB  - BACKGROUND: Physicians play an important role in clinical trials, but attitudes
      toward clinical trials among physicians with different levels of experience have
      seldom been studied. The objective of this study was to assess the different
      attitudes toward clinical trials among junior, intermediate, and senior
      physicians. METHODS: An anonymous cross-sectional survey was conducted between
      April 1 and May 1, 2015. A total of 217 physicians (66 junior, 86 intermediate,
      and 65 senior positions) completed and submitted the validated questionnaires.
      RESULTS: The surveyed physicians responded with a high degree of agreement on the
      necessity of conducting clinical trials. Senior and intermediate physicians
      considered most about helping patients with new treatments in conducting a
      clinical trial. For junior physicians, the opportunity to have access to clinical
      trial methodology and enhancing their reputation in society or in the hospital
      were the 2 most significant factors. In addition, physicians with lower titles
      perceived greater difficulties in conducting clinical trials, especially in
      communicating with the Good Clinical Practice (GCP) office and the trial sponsor,
      enrolling trial participants, and obtaining informed consent. CONCLUSIONS: Our
      results revealed that physicians with different positional titles perceived
      different benefits and difficulties in conducting clinical trials. Junior
      physicians need more administrative assistance in clinical trials and related
      training.

PMID- 30231757
TI  - Regulation of New Drug Approval in Taiwan.
AB  - Taiwan Food and Drug Administration (TFDA) was established in 2010 as the
      nation's principal consumer product protection agency of food, drugs, medical
      devices, and cosmetics. By integrating 4 agencies (the Bureau of Food Safety,
      Bureau of Pharmaceutical Affairs, Bureau of Food and Drug Analysis, and Bureau of
      Controlled Drugs), TFDA holds the mission of protecting and promoting the public
      health through regulation modernization to enhance the availability of safe
      medical products and foods. To address the unmet medical needs and public health,
      TFDA has utilized regulatory science to evaluate review principles and risk
      management to properly oversee the overall life cycle of medicinal products. A
      lot of measures have been accomplished to build an efficient, transparent, and
      internationally harmonized regulatory system. With the first-in-the-world new
      drug afatinib approved in Taiwan, TFDA has successfully built up capacity and
      capability in the review and approval of new drugs. This article summarizes the
      efforts TFDA has been making in the domain of medicinal product management,
      highlighting policies and strategies for the future.

PMID- 30231758
TI  - The Early Engagement Model in Product Development: Linking "Proof of Concept" to
      "Proof of Medical Value".
AB  - In a rapidly changing health care environment, it is more important than ever
      that pharmaceutical manufacturers improve the quality and efficiency of their
      research and development efforts in order to help ensure the right drug gets to
      the right patient at the right time. The evolving role of the Medical Affairs,
      Health Economics & Outcomes Research (HEOR) and other functions engaged in
      evidence generation within the pharmaceutical industry is leading to earlier
      involvement in the clinical development process so that the proof of concept for
      new therapies can be more strongly linked to the proof of medical value. In this
      article, the authors outline key components of an Early Engagement Model that
      connects the proof of concept to proof of medical value through a systematic
      approach linking molecular profile with early insights on disease, unmet needs,
      stakeholder requirements, and patient-centric differentiation.

PMID- 30231759
TI  - A Knowledge Management Framework and Approach for Clinical Development.
AB  - A knowledge management (KM) framework enhances knowledge gathering, sharing,
      application, and retention within clinical development and enables the effective
      and successful implementation of a clinical quality management system (QMS). The
      goal of managing knowledge is to improve organizational performance by getting
      the right information to the right people at the right time. The concepts of KM
      have been around for decades but, to date, have not been widely adopted within
      the clinical development arena. Implementing a structured approach and strategy
      to managing knowledge can enable more timely and informed decision making,
      enhance quality and productivity, and ultimately support the delivery of new
      products to patients. This paper outlines in general terms key elements of a
      clinical knowledge management (CKM) framework to assist clinical development
      organizations in understanding its benefits and basic components. Ideas are
      provided at a high level for flexible approaches and solutions aimed to enhance
      knowledge gathering, sharing, application, and retention within clinical
      development.

PMID- 30231760
TI  - Responsibilities of Data Monitoring Committees: Consensus Recommendations.
AB  - BACKGROUND: A data monitoring committee (DMC) has special responsibilities for
      protecting the safety of clinical trial participants. Few guidance documents are
      available that address the operations and mechanics of establishing, serving on,
      or reporting to a DMC. This article provides a practical guide to sponsors,
      institutions, and individuals responsible for, or serving on, a DMC. METHODS: A
      workgroup of professionals from academia and not-for-profit and commercial
      organizations that included investigators, statisticians, patient advocates, and
      ethicists met to define the essential elements of planning, coordinating, and
      populating a DMC. All members of the group have formed, served on, advised, or
      worked with DMCs. RESULTS: The group outlined the objectives and mechanics of
      running a DMC, including operational and practical considerations, membership
      characteristics, roles, members' liability, and indemnification. Further, it
      delineated the roles and responsibilities of each DMC member. CONCLUSIONS: The
      group recommended practices for each phase of the DMC process from inception
      through execution of a clinical trial, with appropriate considerations for
      confidentiality. The group's practical guidance should assist in comprehensive
      oversight of appropriate clinical trials and should help DMC members execute
      their obligations with greater assurance.

PMID- 30231761
TI  - Pragmatic Multicriteria Decision Analysis (MCDA) Combined With Advanced
      Pharmacoepidemiology for Benefit-Risk Assessments of Medicines Adapted to the
      Real-Life Constraints of Regulators: Development and Case Study.
AB  - BACKGROUND: Multicriteria decision analysis (MCDA) represents a promising method
      for benefit-risk assessment. Our goal was to develop features of pragmatic MCDA
      (EVIDEM [Evidence and Value: Impact on DEcisionMaking]) addressing real-life
      regulatory decision-making needs, incorporate advanced pharmacoepidemiology, and
      test the resulting benefit-risk framework using a case study. METHODS: The
      Intervention Outcomes domain of EVIDEM was transformed into a generic benefit
      risk framework including clinical efficacy, patient-reported outcomes, and
      adverse event (AE) criteria. The concept of relative benefit-risk balance (RBRB)
      was developed for comparability across products and therapeutic areas and over
      time. Evidence matrix was designed to include most relevant data from trials,
      observational studies, and models, including Bayesian and longitudinal modeling.
      The framework was tested with a panel of stakeholders using efalizumab for
      psoriasis as retrospective case study. Uncertainty was explored. RESULTS: The
      MCDA benefit-risk tree was adapted with psoriasis-specific subcriteria. Panelists
      assigned similar weights to benefits (0.48; SD, 0.20-0.70) and risks (0.52; SD,
      0.10-0.60), with large variations reflecting diverse perspectives. Panelist
      scores reflected higher efficacy versus placebo, lower efficacy versus active
      comparators, and serious and fatal AEs identified postlicensing. Efalizumab's
      RBRB was positive at licensing in 2004 (0.29, scale -1 to +1) and ranged from 
      0.41 (vs active comparators) to 0.01 (vs placebo) in 2009, when its market
      authorization was withdrawn. Retesting indicated good reproducibility. Panelists
      acknowledged good face validity and the importance of criteria beyond benefit
      risk in real-life assessments. CONCLUSIONS: The approach allows quantification
      and visualization of benefit-risk over time and across comparators. Combination
      of pragmatic MCDA designed to integrate criteria beyond benefit-risk and advanced
      statistics supports application of MCDA to further accountable benefit-risk
      assessments for real-life decision making.

PMID- 30231762
TI  - A Patient Centricity Team Tool to Enable Patient-Focused Drug Development.
AB  - In order to better understand and advance the field of patient-focused drug
      development, a multifunctional patient affairs team developed and piloted a
      Patient Centricity Team Tool (PCTT) within a large pharmaceutical organization.
      The tool is a computer-based survey designed to interrogate the frequency of team
      efforts in 20 areas of patient centricity across 4 dimensions: people, purpose,
      process, and actions. Results from a pilot with a Phase III product team indicate
      a spectrum of team activity of different frequencies related to patient-focused
      drug development. Given the lack of tool validation, interpretation of results
      remains a reflection of the team, asset, and lifecycle stage as opposed to a
      diagnostic of activities. Over time and with increased use across teams, tool
      implementation and associated learnings may yield organizational, product, and
      ultimately patient benefits.

PMID- 30231763
TI  - TransCelerate's Clinical Quality Management System: Issue Management.
AB  - Issue management is one of the elements of the TransCelerate clinical quality
      management (QMS) conceptual framework. Effective issue management benefits
      clinical development organizations by allowing them to focus efforts on those
      issues that materially impact patient safety, rights, and well-being; data
      integrity and/or scientific rigor; compliance with regulatory requirements; or
      trust in the clinical research enterprise, which have been defined as "Issues
      that Matter." Issue management begins with a triage of issues to identify those
      issues that materially impact as defined above, which are then handled by an end
      to-end corrective and preventive action (CAPA) process. An added benefit of a
      well-defined issue management framework is the capability for trending and
      analytics designed to provide data and insights into risk management and
      knowledge management efforts.

PMID- 30231764
TI  - Improving Information Processing: The Effect of Label Format Among Current and
      Potential Over-the-Counter Medication Users.
AB  - OBJECTIVE: To test the effect of current versus 2 experimental label formats on
      information processing among current and potential over-the-counter (OTC) users.
      METHODS: A cross-sectional survey was conducted in a cohort of adults across a
      metropolitan community, Houston, Texas. Three labels were designed. We placed a
      chunk of like information together (uses, direction, other information). Label A
      (control) followed the format of the existing FDA Drug Facts panel format for an
      antiallergy medication, label B had warnings placed before, while label C had
      warnings placed after the chunk. The 2 label designs were compared using the
      information-processing constructs derived from the OTC Label Evaluation Process
      Model (LEPM). RESULTS: A multivariate analysis of covariance and Dunnett's test
      revealed that the mean scores for constructs of OTC LEPM were significantly
      better for label C compared to the control and label B ( P < .0001). CONCLUSION:
      Our label format improved information processing among consumers but only when
      warning placement was placed at the end in the Drug Facts panel, giving an
      opportunity for the FDA to consider revising the format of the OTC Drug Facts
      panel, to improve patient understanding and reciprocally enhance patient safety.

PMID- 30231765
TI  - Product Development Under FDA's Animal Rule: Understanding FDA's Expectations and
      Potential Implications for Traditional Development Programs.
AB  - In 2002 the US Food and Drug Administration (FDA) established a regulatory
      pathway for drug and biological products targeting indications for which human
      efficacy studies are not feasible or ethical. These regulations (21 CFR 314.600
      for drugs and 21 CFR 601.90 for biologics), commonly referred to as the "Animal
      Rule," were the result of many years of thinking about how to make such products
      available to people who might need them. A handful of products have been approved
      under the Animal Rule, and several others are in development. This article
      reviews how different products met the requirements for licensure under the
      Animal Rule, based on information publicly available on FDA's website. The
      primary aim of this manuscript is to offer an understanding of FDA's
      interpretation of relevant regulations and guidances in the context of this
      licensure pathway. Some of the methods used for Animal Rule approvals may also
      have potential application in more traditional development programs. Thus, this
      article may also offer insight into methods for accelerating product development
      in general.

PMID- 30231766
TI  - Survey of Health Care Practitioners' Preferences for Medical Information:
      Collective Insights for Impacting Patient Care.
AB  - BACKGROUND: Medical information (MI) departments play an integral role in
      providing fair and scientifically balanced MI to health care professionals,
      patients, and caregivers. Though there have been multiple surveys conducted to
      assess the value of MI, insights on what the informational needs are from the
      perspective of the health care professional to confidently making patient care
      decisions have not been addressed. A survey administered to health care
      professionals that collected insights and feedback on the utility of MI services
      across different pharmaceutical companies provided an understanding of the
      informational needs of different health care professionals for prescribing drug
      therapy with confidence. METHODS: A total of 276 health care professionals who
      requested medical information in a 6-month time frame from 8 companies completed
      a 30-minute Internet-based survey (n = 260) or a 20-minute telephone survey (n =
      16). RESULTS: Most health care professionals preferred obtaining medical
      information from traditional routes such as discussions with sales
      representatives or via the telephone, while very few preferred alternate routes
      such as mobile applications, video chats, or text. The type of medical
      information requested among practitioners included topics related to dosing,
      safety, patient selection, and differentiating between therapeutic options. When
      making patient care decisions, health care professionals identified 3 levels of
      evidence-prospective studies, practice guidelines, and meta-analyses-to be most
      important. Medical information responses were used for education purposes and
      provided physicians the confidence to make treatment decisions. For nurse
      practitioners/physician assistants, nurses, and pharmacists, the information
      provided by MI departments enhanced the quality of patient management.
      CONCLUSIONS: These findings provide information regarding the utility of medical
      information services while providing insights on the informational needs of
      health care professionals today. MI departments provide an important service to
      health care professionals that impart confidence for making treatment decisions.

PMID- 30231767
TI  - Do Patients Use a Headline Section in a Leaflet to Find Key Information About
      Their Medicines? Findings From a User-Test Study.
AB  - BACKGROUND: In the European Union (EU), all medicines are mandated to be provided
      with a patient information leaflet (PIL). Many patients express concerns about
      the length and complexity of some PILs, and this can be a disincentive for
      patients to read the PILS. In order to address this, the UK's regulatory body
      (Medicine and Healthcare products Regulatory Agency [MHRA]) suggested leaflets
      might include a headline section-information presented prominently at the
      beginning of a leaflet that summarizes key safety messages about a drug.
      OBJECTIVE: To explore the extent to which readers used a headline section in a
      PIL, using a form of diagnostic testing called user-testing, which examines how
      readers find and understand key information. METHODS: The study used a cross
      sectional design to user-test a PIL with a headline section in a target sample of
      20 participants. Participants were provided with an exemplar PIL, and the
      performance of the PIL was evaluated by a questionnaire and semistructured
      interview. RESULTS: The results showed that a headline section was used just over
      one-third of the time (39%); 90% of participants used the headline section to
      find information when they initially began the user-test. The qualitative
      findings suggested that the participants valued the presence of the headline
      section. CONCLUSION: The research suggests there does not appear to be any
      negative impact from including a headline section in a PIL, and it is a technique
      that is highly valued by the consumers of medicines information.

PMID- 30231768
TI  - Nurse Prescribing From the Global Vantage Point: The Intersection Between Role
      and Policy.
AB  - Nurses around the world are increasingly prescribing and managing pharmaceutical
      agents. Prescribing by nurses is currently based on varying nursing roles,
      depending on national and regional norms and practices. Prescribing occurs within
      the advance practice, advanced level, and task-sharing roles, depending on the
      country. It is evolving both within and outside of traditional regulatory
      frameworks. Therefore, the purpose of this article is to describe the nurse
      prescribing globally among various nursing roles that support and facilitate the
      practice. We gathered practice, statutory, and regulatory information from gray
      and peer-reviewed literature, Google search and Google scholar, government
      websites, PubMed, and CINAHL electronic databases. In contrast to previous global
      policy reviews that focus primarily on high-income nations, our findings suggest
      that nurse prescribing occurs extensively in all six continents. Nurse
      prescribing within the context of advanced practice nursing occurs mostly in high
      income countries. However, the predominant model of nurse prescribing from the
      global context occurs within the advanced level role by postbasic or
      postprofessional nurses. Additional nurse prescribing occurs through less formal
      task-sharing arrangements, primarily in low- to middle-income countries. In
      general, nurse prescribing is evolving rapidly around the world but within highly
      variable roles and regulatory frameworks. Codifying these roles by strengthening
      of educational and regulatory standards may serve to enhance the health system
      capacity, especially in low- to middle-income countries.

PMID- 30231769
TI  - Effect of Physical Exercise on Endometriosis Experimentally Induced in Rats.
AB  - OBJECTIVE: Endometriosis is characterized by the growth of endometrial tissue
      outside the uterine cavity. The prevalence of endometriosis among women
      experiencing pain, infertility, or both is as high as 35% to 50%. The most common
      symptoms of endometriosis are dysmenorrhea, dyspareunia, chronic pelvic pain, and
      infertility. Evidence has suggested that endometriosis symptoms result from a
      local inflammatory peritoneal reaction caused by ectopic endometrial implants
      that undergo cyclic bleeding. On the other hand, regular physical exercise seems
      to have protective effects against diseases that involve inflammatory processes
      such as type 2 diabetes and colon and breast cancer. On this basis, it is
      possible that the practice of physical exercise may have beneficial effects on
      endometriosis. Therefore, the objective of this study was to evaluate the
      possible anti-inflammatory effect of physical exercise on endometriosis
      experimentally induced in rats. STUDY DESIGN: Seventy female Wistar rats were
      divided into 7groups of 10 animals each. Animals performed light exercise
      (swimming once a week), moderate exercise (swimming 3 times a week), and intense
      exercise (swimming 5 times a week) before or after endometriosis induction.
      RESULTS: At the end of the experimental protocol, a reduction in the size of
      endometriotic lesions was observed after physical exercise regardless of its
      frequency, with a greater reduction in the groups practicing moderate and intense
      activity; an increase in FAS levels and a decrease in matrix metalloproteinases 9
      and proliferating cell nuclear antigen (PCNA)levels was also observed. The
      immunohistochemistry results did not lead to conclusive results. As expected,
      oxidative stress was reduced in all groups. These results show that the practice
      of physical exercise could be beneficial, at least in part, for the treatment of
      endometriosis.

PMID- 30231770
TI  - A zero-waste process for the management of MSWI fly ashes: production of ordinary
      Portland cement.
AB  - Municipal solid waste incineration (MSWI) fly ashes are hazardous waste since
      they contain organic pollutants, heavy metals and an important amount of various
      soluble salts. However their chemical composition is interesting for their
      valorization in cement production. The objective of this paper is to assess the
      possibility of MSWI fly ashes reuse as cement raw meal, after pre-treatment, at a
      laboratory scale. The environmental impact has also been studied (analyses of the
      metals, of dioxins and furans and leaching tests on clinker produced).
      Experimental results show that the replacement of MSWI fly ash could be taken up
      to 30% in the raw mixes, according to the chemical composition of the MSWI fly
      ashes. This substitution is also to be refined according to the content of
      hazardous elements contents. This study also shows that the pre-treatment must be
      well carried out in order to limit the alkaline contents which may affect the
      quality of the cementitious phases.

PMID- 30231772
TI  - Maternal exposure to di-n-butyl phthalate induces alterations of c-Myc gene, some
      apoptotic and growth related genes in pups' testes.
AB  - The aim of this study was to investigate the effects of maternal exposure to di-(
      n-butyl) phthalate (DBP) on testicular development and function in pre-pubertal
      and post-pubertal male rat offspring. Fourteen pregnant female rats were equally
      divided into two groups: a control group and a DBP-treated group. During
      gestation day (GD) 12 to postnatal day (PND) 14, the control group was
      administered 1 ml/day corn oil, and the DBP-treated group was administered DBP
      500 mg/kg/day by oral gavage. On PND 25 (pre-puberty) and PND 60 (post-puberty),
      blood for serum and the testes were collected from five male offspring of each
      group. To determine the relationship between the methylation state of the c-Myc
      promoter and the expression of the c-Myc gene, some apoptotic-related genes, such
      as p53 and Bax, the anti-apoptotic Bcl-2 gene, and some growth arrest-related
      genes, such as BRD7 and GAS1, were examined. Compared with the control ( p <
      0.05), at pre-puberty, DBP induces c-Myc hyper-methylation with significant
      downregulation for c-Myc, p53, Bax genes, and significant upregulation for Bcl-2,
      BRD7, and GAS1, while at post puberty, the methylation state and expression of c
      Myc and apoptosis-related genes returned to control levels in the same sequence
      with the fold change in the expression of BRD7 and GAS1 genes. These findings
      suggest that DBP induced a transient pre-pubertal increase in c-Myc promoter
      methylation that may be associated with disruption of both apoptotic and growth
      mechanisms in the testes.

PMID- 30231774
TI  - Endometrial miR-543 Is Downregulated During the Implantation Window in Women With
      Endometriosis-Related Infertility.
AB  - BACKGROUND: Differentially expressed microRNAs (miRNAs) and their target mRNAs
      may lead to alterations in normal physiological status of the tissues and
      initiate pathological processes. The aim of this study was to investigate the
      expression of the most relevant miRNAs in the eutopic endometrial tissue during
      the window of implantation in women with endometriosis-related infertility.
      METHODS: In the study, 76 infertile women with a regular menstrual cycle were
      recruited from the Center for Reproductive Medicine, Peking University Third
      Hospital between January 2014 and June 2016. We performed a combined messenger
      RNA and miRNA microarray and bioinformatics analysis of eutopic endometrium in 6
      women with and without endometriosis-related infertility at the time of
      implantation window. Quantitative real-time polymerase chain reaction arrays were
      utilized to examine the expression levels of selected miRNAs (from 35 patients
      with endometriosis and 35 disease-free individuals at different menstrual
      stages). RESULTS: Five differentially expressed miRNAs (miR-142-5p, miR-146a-5p,
      miR-1281, miR-940, and miR-4634) were significantly upregulated, whereas miR-543
      was significantly downregulated in the eutopic endometrium during the window of
      implantation in patients with endometriosis. Further analysis showed that miR-543
      was significantly upregulated at the peri-implantation phase compared with that
      at proliferative phase in the endometrium of disease-free patients ( P < .05).
      However, the expression level of miR-543 was significantly decreased in patients
      with endometriosis ( P < .05), especially downregulated at the window of
      implantation phase ( P < .05). CONCLUSIONS: miR-543 plays an important role
      during embryo implantation process and is associated with endometrial
      receptivity. Downregulation of miR-543 may affect embryo implantation, resulting
      in the pathogenesis of endometriosis-related infertility.

PMID- 30231775
TI  - Stereotactic Body Radiotherapy as an Alternative to Definitive Surgery in Cancers
      of Various Organs.

PMID- 30231773
TI  - Long-term outcome of elderly out-of-hospital cardiac arrest survivors as compared
      with their younger counterparts and the general population.
AB  - BACKGROUND:: Over the past decade, prehospital and in-hospital treatment for out
      of-hospital cardiac arrest (OHCA) has improved considerably. There are sparse
      data on the long-term outcome, especially in elderly patients. We studied whether
      elderly patients benefit to the same extent compared with younger patients and at
      long-term follow up as compared with the general population. METHODS:: Between
      2001 and 2010, data from all patients presented to our hospital after OHCA were
      recorded. Elderly patients (?75 years) were compared with younger patients.
      Neurological outcome was classified as cerebral performance category (CPC) at
      hospital discharge and long-term survival was compared with younger patients and
      predicted survival rates of the general population. RESULTS:: Of the 810 patients
      admitted after OHCA, a total of 551 patients (68%) achieved return of spontaneous
      circulation, including 125 (23%) elderly patients with a mean age of 81 +/- 5
      years. In-hospital survival was lower in elderly patients compared with younger
      patients with rates of 33% versus 57% ( p < 0.001). A CPC of 1 was present in 73%
      of the elderly patients versus 86% of the younger patients ( p = 0.031). In 7.3%
      of the elderly patients, a CPC >2 was observed versus 2.5% of their younger
      counterparts ( p = 0.103). Elderly patients had a median survival of 6.5 [95%
      confidence interval (CI) 2.0-7.9] years compared with 7.7 (95% CI 7.5-7.9) years
      of the general population ( p = 0.019). CONCLUSIONS:: The survival rate after
      OHCA in elderly patients is approximately half that of younger patients. Elderly
      patients who survive to discharge frequently have favorable neurological outcomes
      and a long-term survival that approximates that of the general population.

PMID- 30231777
TI  - Impact of bariatric surgery on cardiovascular and renal complications of
      diabetes: a focus on clinical outcomes and putative mechanisms.
AB  - INTRODUCTION: Cardiovascular and renal disease accounts for a substantial
      proportion of the morbidity and mortality associated with obesity and type 2
      diabetes mellitus (T2DM). Bariatric surgery is associated with improved long-term
      cardiovascular and renal outcomes. Areas covered: All major case-control, cohort,
      and randomized controlled trial studies of bariatric surgery in adults with T2DM
      were screened and data on prespecified cardiovascular and renal outcomes
      collated. Bariatric surgery reduces all-cause mortality and risk of
      cardiovascular disease, albuminuria and progressive chronic kidney disease.
      Patients with poorer glycemic control and established microvascular disease
      preoperatively may stand to benefit the most from the surgical approach. Reduced
      sympathetic drive, remission of glomerular hypertension, enhanced natriuresis,
      gut microbiota shifts, reduced systemic and renal inflammation, improved
      lipoprotein profiles, and reductions in chronic cardiac remodeling may all be
      implicated. Expert commentary: Ongoing RCTs of bariatric surgery selectively
      recruiting patients with class 1 obesity and established microvascular
      complications of diabetes will help to better characterize which subgroups of
      patients benefit most from this effective therapy.

PMID- 30231776
TI  - Characterization of Cell Membrane Permeability In Vitro Part II: Computational
      Model of Electroporation-Mediated Membrane Transport.
AB  - Electroporation is the process by which applied electric fields generate
      nanoscale defects in biological membranes to more efficiently deliver drugs and
      other small molecules into the cells. Due to the complexity of the process,
      computational models of cellular electroporation are difficult to validate
      against quantitative molecular uptake data. In part I of this two-part report, we
      describe a novel method for quantitatively determining cell membrane permeability
      and molecular membrane transport using fluorescence microscopy. Here, in part II,
      we use the data from part I to develop a two-stage ordinary differential equation
      model of cellular electroporation. We fit our model using experimental data from
      cells immersed in three buffer solutions and exposed to electric field strengths
      of 170 to 400 kV/m and pulse durations of 1 to 1000 MUs. We report that a low
      conductivity 4-(2-hydroxyethyl)-1 piperazineethanesulfonic acid buffer enables
      molecular transport into the cell to increase more rapidly than with phosphate
      buffered saline or culture medium-based buffer. For multipulse schemes, our model
      suggests that the interpulse delay between two opposite polarity electric field
      pulses does not play an appreciable role in the resultant molecular uptake for
      delays up to 100 MUs. Our model also predicts the per-pulse permeability
      enhancement decreases as a function of the pulse number. This is the first report
      of an ordinary differential equation model of electroporation to be validated
      with quantitative molecular uptake data and consider both membrane permeability
      and charging.

PMID- 30231780
TI  - Correction.

PMID- 30231779
TI  - Rapidly screening of alpha-glucosidase inhibitors from Dioscorea opposita Thunb.
      peel based on rGO@Fe3O4 nanocomposites microreactor.
AB  - Present study aimed to immobilise the alpha-glucosidase on suitable supports to
      construct enzymatic microreactors and their subsequent applicability in efficient
      inhibitor screening from the Chinese Yam (Dioscorea opposita Thunb.) peel. A type
      of lamellar and porous composites (rGO@Fe3O4) were synthesised with a facile one
      step solvothermal method and employed as carriers to construct enzymatic
      microreactors for screening alpha-glucosidase ligand from the Chinese Yam peel in
      league with the high performance liquid chromatography and mass spectrometry
      (HPLC-MS). The immobilisation amount of alpha-glucosidase on rGO@Fe3O4 under the
      optimised conditions was about 40 MUg alpha-glucosidase/mg carriers. Furthermore,
      the binding capacities of screened inhibitors, 2,4-dimethoxy-6,7
      dihydroxyphenanthrene and batatasin I, were 35.6 and 68.2%, respectively. Hence,
      considering their high screening efficiency and excellent magnetic separation
      ability, these as-prepared nanocomposite consisting of rGO and Fe3O4 may be
      potential supports for the enzyme (such as alpha-glucosidase) immobilisation for
      rapid alpha-glucosidase inhibitors screening from the diverse nature resources.

PMID- 30231781
TI  - Risk factors for obstetric anal sphincter injuries (OASIS) during vacuum
      extraction delivery in a university affiliated maternity hospital.
AB  - INTRODUCTION: Instrumental delivery is a well-known risk factor for obstetric
      anal sphincter injuries (OASIS). The specific characteristics among patient
      undergoing vacuum extraction delivery (VE) are less studied. Therefore, we aimed
      to evaluate risk factors for OASIS among parturient that underwent a VE delivery
      in a large university affiliated maternity hospital. MATERIAL AND METHODS: The
      study population contained 9116 women who delivered by VE in tertiary medical
      center from 1988 to 2015. Inclusion criteria included deliveries beyond 24-week
      gestation. Multiple gestations and pregnancies complicated with stillbirth were
      excluded from the analysis. Maternal obstetric variables were compared between
      parturient with and without OASIS. Independent risk factors for OASIS were
      assessed by multivariable logistic regression modeling. RESULTS: OASIS was
      diagnosed in 94 women (1.03%) following vacuum extraction. Among patients who
      underwent a VE delivery, gravidity and parity were found to be significantly
      lower in patients with OASIS. A multivariable logistic regression model with
      OASIS as the outcome variable revealed that among women who underwent VE, while
      episiotomy and delivery of a macrosomic neonate were not independently associated
      with OASIS, a strong association between nulliparity and OASIS was found (OR
      3.34; 95% CI 1.93-5.78; p < .001). CONCLUSIONS: OASIS is uncommon in our
      population. Vacuum extraction in nulliparous parturient is a significant risk
      factor for OASIS. Our results should be taken into account when managing
      nulliparous deliveries.

PMID- 30231778
TI  - Synthesis and biological evaluation of pyrrolidine-based T-type calcium channel
      inhibitors for the treatment of neuropathic pain.
AB  - The treatment of neuropathic pain is one of the urgent unmet medical needs and T
      type calcium channels are promising therapeutic targets for neuropathic pain.
      Several potent T-type channel inhibitors showed promising in vivo efficacy in
      neuropathic pain animal models and are being investigated in clinical trials.
      Herein we report development of novel pyrrolidine-based T-type calcium channel
      inhibitors by pharmacophore mapping and structural hybridisation followed by
      evaluation of their Cav3.1 and Cav3.2 channel inhibitory activities. Among potent
      inhibitors against both Cav3.1 and Cav3.2 channels, a promising compound 20n
      based on in vitro ADME properties displayed satisfactory plasma and brain
      exposure in rats according to in vivo pharmacokinetic studies. We further
      demonstrated that 20n effectively improved the symptoms of neuropathic pain in
      both SNL and STZ neuropathic pain animal models, suggesting modulation of T-type
      calcium channels can be a promising therapeutic strategy for the treatment of
      neuropathic pain.

PMID- 30231782
TI  - Influence of low-glycemic index diet for gestational diabetes: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Low-glycemic index (GI) diet might be beneficial for gestational
      diabetes. However, the results remained controversial. We conducted a systematic
      review and meta-analysis to explore the influence of low-GI diet on gestational
      diabetes. METHODS: PubMed, EMbase, Web of Science, EBSCO, and Cochrane library
      databases were systematically searched. Randomized controlled trials (RCTs)
      assessing the effect of low-GI diet on gestational diabetes were included. Two
      investigators independently searched articles, extracted data, and assessed the
      quality of included studies. This meta-analysis was performed using the random
      effect model. RESULTS: Six RCTs involving 532 patients were included in the meta
      analysis. Overall, compared with a control intervention in gestational diabetes,
      low-GI diet was found to significantly reduce 2 h postprandial glucose (Std. MD =
      -0.46; 95% CI = -0.82 to -0.10; p = .01), but demonstrated no substantial
      influence on fasting plasma glucose (Std. MD = -0.24; 95% CI = -0.72 to 0.24; p =
      .33), HbA1c (Std. MD = 0.01; 95% CI = -0.29 to 0.31; p = .94), birth weight (Std.
      MD = -0.17; 95% CI = -0.41 to 0.06; p = .15), macrosomia (Std. MD = 0.45; 95% CI
      = 0.16 to 1.30; p = .14) and insulin requirement (Std. MD = 0.91; 95% CI = 0.68
      to 1.22; p = .55). CONCLUSIONS: Compared with control intervention in gestational
      diabetes, low-GI diet was found to significantly decrease 2 h postprandial
      glucose, but showed no notable impact on fasting plasma glucose, HbA1c, birth
      weight, macrosomia, and insulin requirement.

PMID- 30231784
TI  - What is the effect of intertwin delivery interval on the outcome of the second
      twin delivered vaginally?

PMID- 30231783
TI  - Description of criteria for near miss in high-complexity obstetric population
      with sickle cell anemia: an observational study.
AB  - INTRODUCTION: Sickle cell disease (SCD) is one of the most common monogenic
      diseases worldwide, affecting approximately 30 million people across the globe.
      It is one of the most common hemoglobinopathies affecting pregnancy, particularly
      in the black population. Pregnant women with SCD, in conjunction with the
      physiological changes of pregnancy, have an increased risk of developing severe
      maternal and fetal complications. MATERIALS AND METHODS: A descriptive,
      observational study was conducted retrospectively to determine the maternal and
      neonatal disease burden of pregnant women with SCD between 2011 and 2016. The
      study included pregnant patients with SCD admitted to the hospital, with
      confirmed diagnosis through hemoglobin electrophoresis. Patients having no
      confirmatory testing of the disease were excluded. RESULTS: In all, 54% (34
      patients) had no previous diagnosis of sickle cell anemia or presence of sickle
      cell trait, and so an in-hospital diagnosis was carried out through hemoglobin
      gel electrophoresis, whereas the remaining 46% (28 patients) had already a
      peripheral diagnosis. In total, the following profiles were obtained: Hb AS 62.9%
      (39 patients), Hb SC 17.7% (11 patients), Hb SS 16.1% (10 patients), Hb AC 3.2%
      (2 patients), and Hb CC 0% (0 patients). Vaso-occlusive pain crises constituted
      the most common cause of hospital admission antepartum (54.8% of the general
      population), occurring in 100% of the patients with Hb SS and Hb AC, in 45% of
      the Hb SC group and in 43% of those with the Hb AS trait. The second cause of
      hospital admission encompassed infectious processes, which affected 45% of the
      general population, 30% of the Hb AS group, 60% of the Hb SS group, 77% of the Hb
      SC group, and 100% of the Hb AC group. The method of termination of pregnancy of
      44% (27 patients) was C-section. The most common perinatal complication was
      preterm birth, occurring in 26% (16 patients), with the highest incidence in the
      Hb AC group. The second most common complication was the intrauterine growth
      restriction, reported in 6% (4 patients) of all patients, being most frequently
      in the Hb SS group. CONCLUSION: Pregnant women having SCD should be assessed and
      managed by a multidisciplinary team composed of hematology, perinatology, and
      intensive care. Management should be conducted preferably in high-quality centers
      experienced in treating this entity, thereby decreasing the great impact of
      morbidity and mortality associated with SCD in the pregnant population.

PMID- 30231785
TI  - T-cell immunoglobulin mucin-3 and galectin-9 levels in peripheral blood
      mononuclear cells predict fetal acidemia in twin pregnancies.
AB  - PURPOSES: The pH in the umbilical artery at delivery provides information on the
      fetal environment and is related to postnatal outcomes. The ability to predict
      fetal acidemia at delivery would improve clinical management and neonatal well
      being. We hypothesized that an alteration in maternal immunity would accompany
      placental changes that precede a decrease in pH in the fetal circulation in twin
      gestations. METHODS: Peripheral blood mononuclear cells (PBMCs), obtained from 86
      women with twin pregnancies, were lysed and assayed for concentrations of T-cell
      immunoglobulin mucin domain 3 (Tim-3) and galectin-9 (gal-9) by ELISA. Tim-3-gal
      9 interaction is a primary mechanism promoting immune suppression. At delivery,
      the pH of arterial cord blood was determined. RESULTS: In eight women (9.3%), the
      pH in the placental arteries from both twins was <7.15, indicating fetal
      acidosis. In the remaining 78 women the arterial pH was >=7.15 in both twins. The
      median Tim-3 level was 361 pg/ml when arterial pH was <7.15 and 199 pg/ml when pH
      was >=7.15 (p = .003). Similarly, gal-9 was 31.2 versus 12.4 ng/ml when pH was
      <7.15 or >=7.15, respectively (p = .001). A Tim-3 concentration >260 pg/ml
      predicted arterial pH <7.15 with a sensitivity of 87.5%, specificity of 79.5% and
      negative predictive value of 98.4%. A gal-9 level >18.4 predicted arterial pH
      <7.15 with a sensitivity of 100%, specificity of 73.8% and a negative predictive
      value of 100%. CONCLUSION: We conclude that elevations in Tim-3 and gal-9 in
      PBMCs during gestation predict the subsequent occurrence of a pH <7.15 in the
      fetal arteries at delivery in twin gestations.

PMID- 30231786
TI  - Effect of exercise on type 2 diabetes-associated cognitive impairment in rats.
AB  - OBJECTIVES: Type 2 diabetes (T2D)-associated cognitive impairment is highly
      prevalent especially among the geriatric population. Here, we investigate the
      role of exercise in T2D-associated cognitive decline in rats. METHODS: T2D was
      induced using high-fat diet (15 days) followed by low-dose STZ (25mg/kg). The T2D
      animals were subjected to aerobic exercise on running wheel for 6 weeks. Effect
      of aerobic exercise on cognitive performance of T2D animals was measured using
      step-down and transfer latency tests. This was followed by the measurement of
      reduced glutathione levels in hippocampal homogenates. We also measured
      hippocampal AchE activity and levels of neuroinflammatory markers such as IL-1
      beta, TNF-alpha and MCP-1. Morphology and density of hippocampal neurons were
      also determined by histopathological studies. RESULTS: Exercise led to the
      following changes in T2D animals. It led to decrease in fasting blood glucose
      level (<250 mg/kg) and HbA1c (8.5 +/- 0.23) compared to diabetic (11.73 +/- 0.14)
      animals and improved insulin resistance. There was an increase in step-down
      latency (p < 0.001) and a decrease in transfer latency (p < 0.01) suggesting
      improved cognitive function. A significant increase in GSH levels (1.828 +/-
      0.024) compared to diabetic group (1.52 +/- 0.03; p < 0.001) and decrease in AchE
      activity (1.4 +/- 0.05) compared to diabetic group (1.65 +/- 0.03; p < 0.05) were
      also observed. It reduced the levels of neuroinflammatory markers such as IL
      1beta, TNF-alpha and MCP-1 (p < 0.01). Hippocampal sections showed higher CA1 and
      CA3 neuronal density (p < 0.001) than T2D group. CONCLUSION: We may conclude that
      aerobic exercise could partially reverse diabetes-associated cognitive decline by
      reducing oxidative stress and inflammatory milieu in T2D animal brain.

PMID- 30231791
TI  - Perspectives on Neuroscience and Behavior.

PMID- 30231787
TI  - The effect of gum chewing on the return of bowel motility after planned cesarean
      delivery: a randomized controlled trial.
AB  - OBJECTIVE: To endorse the impact of chewing gum on the intestinal functions'
      restoration, hospital stay and gastrointestinal complications after planned
      cesarean delivery (CD). METHODS: Women aged between 20 and 35 years scheduled for
      planned CD; either first or repeated, with term, singleton, viable and healthy
      pregnancy at obstetrics and gynecology department, Armed Forces Hospital Southern
      Region, Khamis Mushayt, Saudi Arabia were invited to participate and randomized
      if eligible into three groups. The first group chewed sugar-free gum 2 h after
      recovery at least for half an hour and at 2-h interval during daytime. The second
      group received oral fluids 6 h postoperatively, while the third group was the
      control group. The primary outcome measure was the time to first passage of
      stool. The secondary outcomes included the time of the first passage of flatus,
      the first hearing of normal intestinal sounds, the duration of hospital stay the
      duration of parenteral therapy by intravenous fluids, the time of initiating
      breast-feeding and the cost of hospital stay. The study was prospectively
      registered at ClinicalTrials.gov (NCT02386748). RESULTS: The study included 372
      women randomized into three groups (124 women in each group). Chewing gum
      significantly improved intestinal recovery with faster onset of bowel movements,
      first audible intestinal sounds, passage of flatus and passage of stool (p =
      .0001). It was associated with significantly shorter duration of hospital stay
      and parenteral therapy duration (p = .0001). Abdominal distension, vomiting and
      ileus postoperatively were significantly higher in nonchewing gum groups. Neither
      paralytic ileus nor side effects were recorded with gum use. CONCLUSION: Chewing
      gum, within 2 h postoperatively, is a simple, safe and well-tolerated
      intervention that can boost rapid intestinal recovery and shorten hospital stay
      after planned cesarean deliveries.

PMID- 30231788
TI  - Structural basis for extremely strong binding affinity of giant ankyrins to
      LC3/GABARAP and its application in the inhibition of autophagy.
AB  - The Atg8/LC3/GABARAP family of proteins binds its physiological binding partners,
      which function in macroautophagy (hereafter autophagy), via recognition of their
      short linear motif, also known as the LC3-interactiong region (LIR) or Atg8
      interacting motif (AIM). The AIM/LIR motif, with the consensus sequence
      [W/F/Y]xx[L/I/V], utilizes the aromatic and hydrophobic residues that bind on the
      surface of Atg8/LC3/GABARAP. Despite modest binding affinity, this interaction is
      essential for efficient autophagy. Here we highlight the recent paper by Li and
      collaborators who discovered the structural basis for a much stronger interaction
      between the LIR motif-containing peptides and LC3/GABARAP. Moreover, they showed
      that these peptides are potent and selective inhibitors of autophagy in cultured
      cells and in C. elegans.

PMID- 30231792
TI  - The impact of omega-3 fatty acid supplementation on glycemic control in patients
      with gestational diabetes: a systematic review and meta-analysis of randomized
      controlled studies.
AB  - BACKGROUND: Omega-3 fatty acid supplementation shows some treatment efficacy for
      gestational diabetes. This systematic review and meta-analysis is conducted to
      investigate the efficacy of omega-3 fatty acid supplementation for glycemic
      control in patients with gestational diabetes. METHODS: The databases including
      PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases are
      systematically searched for collecting the randomized controlled trials (RCTs)
      regarding the efficacy of omega-3 fatty acid versus placebo for gestational
      diabetes. RESULTS: This meta-analysis has included seven RCTs. Compared with
      placebo group in patients with gestational diabetes, omega-3 fatty acids
      supplementation results in remarkably reduced fasting plasma glucose (FPG)
      (standard mean difference (std. MD) = -0.56; 95% confidence interval (CI) = -0.87
      to -0.24; p = .0005), homeostatic model of assessment for insulin resistance
      (HOMA-IR) (std. MD = -0.52; 95% CI = -0.83 to -0.21; p = .001), but has no
      statistical impact on macrosomia (risk ratio (RR) = 0.48; 95% CI = 0.22-1.02; p =
      .06), newborns' hyperbilirubinemia (RR = 0.46; 95% CI = 0.19-1.10; p = .08),
      nitric oxide (NO) (std. MD = 0.17; 95% CI = -0.64-0.98; p = .68), preterm
      delivery (RR = 1.75; 95% CI = 0.08-3.80; p=.16) and preeclampsia (RR =0.74; 95%
      CI = 0.26-2.16; p = .59). However, notably decreased high sensitivity C-reactive
      protein (hs-CRP) is revealed after omega-3 fatty acids supplementation (std. MD =
      -1.14; 95% CI = -2.0 to -0.29; p = .009). CONCLUSIONS: Omega-3 fatty acids
      supplementation can provide substantially beneficial effects on glycemic control
      and inflammatory response for gestational diabetes.

PMID- 30231793
TI  - 'I know how stressful it is to lack water!' Exploring the lived experiences of
      household water insecurity among pregnant and postpartum women in western Kenya.
AB  - There is rapidly evolving literature on water insecurity in the general adult
      population, but the role of water insecurity during the vulnerable periods of
      pregnancy and postpartum, or in the context of HIV, has been largely overlooked.
      Therefore, we conducted an exploratory study, using Go Along interviews, photo
      elicitation interviews, and pile sorts with 40 pregnant and postpartum Kenyan
      women living in an area of high HIV prevalence. We sought to (1) describe their
      lived experiences of water acquisition, prioritisation, and use and (2) explore
      the consequences of water insecurity. The results suggest that water insecurity
      is particularly acute in this period, and impacts women in far-reaching and
      unexpected ways. We propose a broader conceptualisation of water insecurity to
      include consideration of the consequences of water insecurity for maternal and
      infant psychosocial and physical health, nutrition, and economic well-being.

PMID- 30231794
TI  - Antennae sense heat stress to inhibit mating and promote escaping in Drosophila
      females.
AB  - Environmental stress is a major factor that affects courtship behavior and
      evolutionary fitness. Although mature virgin females of Drosophila melanogaster
      usually accept a courting male to mate, they may not mate under stressful
      conditions. Above the temperature optimal for mating (20-25  degrees C),
      copulation success of D. melanogaster declines with increasing temperature
      although we observed vigorous courtship attempts by males, and no copulation
      takes place at temperatures over 36  degrees C. We attempted to identify the
      sensory pathway for detecting heat threat that drives a female to escape rather
      than to engage in mating that detects hot temperature and suppresses courtship
      behavior. We found that the artificial activation of warmth-sensitive neurons
      ('hot cells') in the antennal arista of females completely abrogates female
      copulation success even at permissive temperatures below 32  degrees C. Moreover,
      mutational loss of the GR28b.d thermoreceptor protein caused females to copulate
      even at 36  degrees C. These results indicate that antennal hot cells provide the
      input channel for detecting the high ambient temperature in the control of virgin
      female mating under stressful conditions.

PMID- 30231795
TI  - The Polymorphism of SREBF1 Gene rs11868035 G/A Is Associated with susceptibility
      to Parkinson's disease in a Chinese Population.
AB  - PURPOSE: To explore the potential association between the single-nucleotide
      polymorphism of two functional genes (SREBF1gene rs11868035 and USP25 gene
      rs2823357) and susceptibility to Parkinson's disease (PD) in people of Northeast
      China. METHODS: 649 cases of Parkinson's disease from consecutive outpatient and
      inpatient ward of our hospital were included in this retrospective study, and 355
      healthy people were also included as control group. The technique of Kompetitive
      Allele Specific PCR (KASP) was applied to determine the frequency distribution of
      genotype and allele gene of rs11868035 and rs2823357 in both groups. RESULTS: The
      significant association was observed for SREBF1 gene rs11868035 in G carriers in
      PD patients. The frequency of GA+GG genotype and G allele in PD group was
      significantly higher than in control group of SREBF1 gene rs11868035 (P < 0.001).
      PD patients with G/A variant got higher UPDRSII+III score and lower MMSE score
      than non-carriers, which was statistically different (P = 0.017, P = 0.003,
      respectively). As for USP25, there was no significant difference in the
      distributions of genotypes and alleles of rs2823357 between PD patients and
      controls (P > 0.05). CONCLUSION: Polymorphism of SREBF1 gene rs11868035 may
      increase susceptibility to Parkinson's disease in the northeastern Chinese
      population, while variant of USP25 gene rs2823357 may have no association with
      susceptibility to Parkinson's disease in northeastern Chinese. PD patients with
      G/A variant may worsen their motor and cognitive function disorder.

PMID- 30231796
TI  - Embolization of a peripheral cerebral aneurysm associated with intracranial major
      artery occlusion through a transdural anastomotic artery: Case report.
AB  - A peripheral cerebral aneurysm is known to develop at collateral vessels as a
      result of hemodynamic stress by the occlusion of the intracranial major arteries.
      We report a case of successful embolization of a ruptured aneurysm through a
      transdural anastomotic artery. The aneurysm formed at the developed collateral
      vessel from the meningeal branch of the occipital artery (OA) to the posterior
      pericallosal artery. A 59-year-old man presented with acute-onset headache, and
      computed tomography revealed subarachnoid hemorrhage and intracerebral hemorrhage
      at the splenium of the corpus callosum with intraventricular hemorrhage. Digital
      subtraction angiography demonstrated a ruptured aneurysm located at a transdural
      anastomotic artery from the right OA to the posterior pericallosal artery. The
      patient underwent endovascular treatment for the aneurysm through the transdural
      anastomotic artery with a coil and n-butyl-2-cyanoacrylate. Because it was
      impossible to navigate a microcatheter to the aneurysm through the right anterior
      cerebral artery because of the occlusion of its proximal portion, it was advanced
      through the transdural anastomosis from the right OA. The aneurysm was completely
      occluded without complications. Endovascular embolization is a useful treatment
      option for a peripheral cerebral aneurysm developed at a collateral vessel with
      intracranial major artery occlusion.

PMID- 30231797
TI  - Endovascular intervention of acute ischemic stroke due to occlusion of fetal
      posterior cerebral artery.
AB  - A fetal posterior cerebral artery (FPCA) is an anatomic variant in which the
      posterior cerebral artery is an embryological derivative of the internal carotid
      artery. Although most cases of ischemic strokes in patients with FPCAs involve
      embolic infarcts, emergent large vessel occlusion of a FPCA is extremely rare. We
      present two cases of successful endovascular intervention for emergent occlusion
      of a FPCA, one of which is only the second reported case of a mechanical
      thrombectomy of a FPCA. We review the embryology of FPCA, the controversy
      regarding its association with cerebral infarcts, and various approaches used in
      the treatment of such occlusive lesions.

PMID- 30231798
TI  - Optimizing contrast-enhanced cone-beam CT protocol to facilitate simultaneous
      visualization of neurovascular pathologies and surrounding structures of
      interest.
AB  - Objective Contrast-enhanced cone-beam computed tomography (CBCT) imaging is
      commonly used for evaluating neurovascular stents and their relationship to the
      parent artery or vascular pathologies such as arteriovenous malformations (AVMs)
      and dural arteriovenous fistulas (dAVFs) in the context of surrounding anatomical
      structures. The purpose of this study was to understand the effects of varying
      concentrations of contrast medium used in CBCT imaging for optimal visualization
      of various endovascular devices and anatomical pathologies. Methods Thirty-five
      patients with various neurovascular pathologies were included in the study.
      Contrast-enhanced CBCT images (20 s DR, Siemens syngo DynaCT, Siemens AG,
      Forchheim, Germany) were acquired in all cases, with varying dilutions of
      contrast medium, from 1% to 30%. The injection rate was kept constant at 3 cc/sec
      with an X-ray delay of two sec, and a total volume of 66 cc of diluted contrast
      was administered. Results from visual and quantitative analysis were reported.
      Results Ten percent dilution of contrast medium resulted in the best image
      differentiation between flow-diverter devices and the parent artery.
      Concentrations as low as 2.5% contrast medium also resulted in identifying AVMs
      in the context of the surrounding brain parenchyma, whereas 20% to 30% dilution
      provided the best visualization of residual AVMs with prior Onyx embolization and
      dAVFs in the presence of bony structures. Conclusions Simultaneous visualization
      of brain parenchyma, bony structures, devices, and pathological anatomy using
      contrast-enhanced CBCT imaging is feasible with appropriate doses of iodinated
      contrast, and should be tailored to the individual case based on the goals of
      CBCT.

PMID- 30231799
TI  - Population structure, genetic diversity and phylogenetic analysis of different
      rural and commercial chickens of Pakistan using complete sequence of mtDNA D
      loop.
AB  - Chicken is the most important poultry bird in Pakistan that not only provides
      nutrition but also contributes to country's economy. The Pakistani chicken and
      its germplasm resources are not genetically characterized and explored. Here, we
      focused at rural and commercial chickens of Pakistan and explored genetic
      diversity, population structure and phylogeny. We first collected feather samples
      from Rural and Broiler populations of Pakistani chickens, isolated DNA and
      sequenced complete D-loop of mtDNA. The length of complete D-loop ranged from
      1231 to 1234 bp in Pakistani chickens. The GC content was 39%. Hotspots of
      mutations were three hypervariable sites (HVS). Most of the variations (77%) were
      in HVS1. In a total, 26 polymorphic sites defined 12 haplotypes and all major
      haplogroups (A-I) in genetic structure of Pakistani chickens. Genetic diversity
      remained relatively very low in Broiler (Pi = 0.00212 +/- 0.00136). There was a
      low sharing of matrilineages between the two populations (Fst = 0.170). With high
      Hd value (0.825 +/- 0.051) and presence of all nine major haplogroups the rural
      chicken population showed relatively rich genepool. Finally we did molecular
      phylogenetic analysis and inferred phylogeny. Presence of subcontinent specific
      haplogroups E3 and I and clustering of Indian red junglefowl closely with
      Pakistani chickens in Bayesian inference tree, provide further evidence for an
      independent domestication event of chicken in subcontinent.

PMID- 30231802
TI  - New-onset lupus nephritis after male-to-female sex reassignment surgery.
AB  - We report an original case of a 27-year-old transgender woman who developed lupus
      nephritis after male-to-female sex reassignment surgery. The patient had been
      taking hormones to induce feminization since the age of 18. She was admitted with
      malar "butterfly" rash, anasarca and hypertension, associated with an increase in
      serum creatinine (1.7 mg/dl). Renal involvement was characterized by nephritic
      and nephrotic syndrome. Autoantibody tests were positive for antinuclear
      antibodies and anti-double-stranded DNA, and complement levels were markedly
      reduced. Renal biopsy demonstrated diffuse proliferative glomerulonephritis and
      granular immune complexes deposits with a "full-house" pattern at the
      immunofluorescence level. The induction treatment was realized with
      corticosteroid and cyclophosphamide and maintenance immunosuppression phase with
      mycophenolate, obtaining complete remission. We speculated that lupus nephritis
      was induced by estrogens and antiandrogen therapy and gonadectomy. In the present
      case, we discuss the role of sex hormones in systemic lupus erythematosus onset
      and review the cases linked to transgender patients.

PMID- 30231800
TI  - Drosophila Caliban mediates G1-S transition and ionizing radiation induced S
      phase checkpoint.
AB  - Cell cycle progression is precisely regulated by diverse extrinsic and intrinsic
      cellular factors. Understanding the underlying mechanisms of cell cycle
      regulation is essential to address how normal development and tissue homeostasis
      are achieved. Here, we present a novel cell cycle regulator Caliban (Clbn), the
      Drosophila ortholog of human Serologically defined colon cancer antigen 1
      (SDCCAG1) gene. We show that ionizing radiation induces expression of clbn, and
      over-expression of clbn blocks G1-to-S cell cycle transition in Drosophila, while
      flies loss of clbn have defective S phase checkpoint in response to irradiation.
      Mechanistically, induced expression of clbn suppressed E2F1 activity and down
      regulates the DNA replication and expression of its downstream target cyclin E, a
      key regulator of G1-to-S transition. Meanwhile, clbn over-expression leads to
      upregulation of the CDK inhibitor Dacapo (Dap), and upregulated Dap is decreased
      when e2f1 is over-expressed. Furthermore, expression of clbn is down-regulated in
      cells with e2f1 over-expression or rbf1 knockdown, indicating that Clbn and E2F1
      act antagonistically in mediating G1-to-S transition. Thus we provide genetic
      evidence that Clbn works together with E2F1 in regulating cell cycle progression,
      and Clbn is required for S phase cell cycle checkpoint in response to DNA damage.

PMID- 30231801
TI  - Short-term changes in added sugar consumption by adolescents reflected in the
      carbon isotope ratio of fingerstick blood.
AB  - BACKGROUND: Consumption of added sugars (AS) and sugar-sweetened beverages (SSB)
      may adversely affect adolescents' weight and cardiovascular disease risk.
      Reliance on self-reported dietary assessment methods is a common research
      limitation, which could be overcome by dietary intake biomarkers. AIM: The
      investigation was a proof-of-concept study to evaluate the proposed carbon
      isotope ratio (delta13C) biomarker of AS intake in adolescents, using a
      controlled feeding design. METHODS: Participants ( n = 33, age 15.3 years, 53%
      female) underwent two seven-day controlled feeding periods in a randomly assigned
      order. Diets were matched in composition except for AS content (5% or 25% of
      total energy). Fasting fingerstick blood samples were collected daily during each
      diet period. RESULTS: Fingerstick delta13C values changed from day 1 to 8 by 
      0.05 +/- 0.0710/00 on 5% AS, and +0.03 +/- 0.0830/00 on 25% AS ( p <= 0.001).
      Reliability was demonstrated between day 7 and 8 delta13C values on the 5% (ICC =
      0.996 , p <= 0.001) and 25% (ICC = 0.997, p <= 0.001) AS diets. CONCLUSIONS:
      Larger scale investigations are warranted to determine if this technique could be
      applied to population-level research in order to help assess the effectiveness of
      interventions aimed at reducing the consumption of AS or SSB intake.

PMID- 30231803
TI  - Deep Femoral Vein Reconstruction of the Abdominal Aorta and Adaptation of the Neo
      Aortoiliac System Bypass Technique in an Endovascular Era.
AB  - BACKGROUND: Primary infection of the abdominal aorta is a rare pathology that may
      threaten the integrity of the aortic wall, while secondary aortic prosthesis
      infection represents a devastating complication to open surgical and endovascular
      aortic surgery. Curative treatment is achievable by removal of all infected
      prosthetic material followed by a vascular reconstruction. DESIGN AND METHODS:
      Twelve consecutive patients treated with the neo-aortoiliac system bypass (NAIS)
      procedure were reviewed. Nine were treated for a secondary aortic prosthesis
      infection (tube graft n = 3, bifurcated graft n = 4, endovascular aortic repair
      (EVAR) stent graft n = 1, and fenestrated EVAR [FEVAR] stent graft n = 1), while
      3 patients underwent NAIS repair due to an emergent primary mycotic aortoiliac
      aneurysm. Primary Results: Ten of 12 patients survived 30 days. Three patients
      were operated on acutely, and 9 patients had elective or subacute NAIS surgery.
      Two of 3 patients operated acutely died within 30 days, whereas no 30-day or 1
      year mortality was observed in patients undergoing elective or subacute surgery.
      The median time from primary reconstruction to the NAIS procedure was 11 months
      (range: 0-201 months). Stent grafts (n = 5 of 12) were in 4 cases explanted using
      endovascular balloon clamping. Of the explanted endografts, 2 patients presented
      with a secondary graft infection after EVAR/FEVAR, while 3 patients had been
      emergently treated with endovascular cuffs as a "bridge-to-surgery" procedure due
      to aortoenteric fistula (AEF). Patients who received a "bridge-to-surgery"
      regimen were treated with the NAIS procedure within 8 weeks (median 27 days,
      range: 27-60) after receiving emergency stent grafting. PRINCIPAL CONCLUSIONS:
      Aortic balloon-clamping during explantation of infected aortic prosthetic
      endografts is feasible and facilitates complete endograft removal. Endovascular
      bridging procedures could be beneficiary in the treatment of AEF or anastomotic
      dehiscence due to graft infection, offering a possibility to convert the acute
      setting to an elective definitive reconstructive procedure with a higher overall
      success rate.

PMID- 30231804
TI  - Anemia following Roux-en-Y gastric bypass for morbid obesity; a 5-year follow-up
      study.
AB  - OBJECTIVES: Patients are at risk of anemia post Roux-en-Y gastric bypass (RYGB).
      We sought to determine the prevalence of anemia and related nutritional
      deficiencies 5 years after RYGB and to evaluate adherence to nutritional
      supplements with iron, vitamin B12, and folate. MATERIAL AND METHODS: Patients
      operated with RYGB 2004-2006 were eligible for evaluation. Blood samples were
      collected and use of nutritional supplements was recorded preoperatively, and at
      outpatients' consultations 1, 2, and 5 years postoperatively. Of 203 patients
      operated, 184 (91%) completed the 5 year follow-up and were included in the
      study. Of these, 97% had valid measurements of hemoglobin both at baseline and
      after 5 years. RESULTS: During the 5 years after RYGB, the prevalence of anemia
      increased from 4% preoperatively to 24% in females, and from 0% to 7% in males.
      Ferritin levels decreased gradually in both genders. Iron deficiency increased
      from 6% preoperatively to 42% at 5 years in females, and from 0% to 9% in males.
      Vitamin B12 deficiency was not altered while folate deficiency decreased from 10%
      preoperatively to 1% at 5 years. Five years after surgery 25% reported the use of
      supplements with iron, while 83% used vitamin B12 and 65% used multivitamins with
      folate. CONCLUSIONS: We observed a long-term increase in anemia and iron
      deficiency after RYGB in both genders, but most pronounced in women. Our
      postoperative protocol for prevention of vitamin B12 and folate deficiencies
      appear acceptable. Iron status and iron supplementation seems to need stronger
      emphasis during follow-up after RYGB.

PMID- 30231805
TI  - Late HCC onset after direct antiviral agents therapy in patients with sustained
      virological response: do we need to reconsider their efficacy according to long
      term follow-up?

PMID- 30231806
TI  - Outcome after accidental food bolus-induced esophageal perforation.
AB  - OBJECTIVES: Food bolus-induced esophageal perforation is much more seldom than
      iatrogenic and emetic esophageal rupture. We present results from a non-operative
      treatment approach as well as long-term functional outcome. MATERIALS AND
      METHODS: Medical records of 10 consecutive patients with food bolus-induced
      esophageal perforation from October 2007 to May 2015 were retrospectively
      registered in a database. Six patients developed perforation related to
      endoscopic removal of impacted food, and four during esophageal passage of bone,
      meat or bread. Treatment was sealing the perforation by stenting (n = 7) with (n
      = 4) or without (n = 3) chest tube drainage, chest tube drainage (n = 1),
      observation (n = 1) and gastroesophageal resection (n = 1) because of concomitant
      emesis of gastric effluent. After median 51 months nine patients reported about
      dysphagia, fatigue and health-related quality of life. RESULTS: Ten patients aged
      median 62.5 years (range 30-85) stayed in our hospital for 12 days (5-68 days).
      There was no treatment-related mortality. Nine patients were alive 63 months (18
      126) after perforation. Five needed restenting (leakage, migration, impacted
      stent), two had drainage of a mediastinal abscess, one patient developed a
      transient esophagobronchial fistula. Dysphagia score was 0 (0-1). One patient
      developed dysphagia for some solid food. Scores for fatigue and HRQoL was similar
      to a Norwegian reference population. CONCLUSION: Treatment mainly with a non
      operative approach occurred without mortality. Complications were handled by
      restenting and abscess drainage. Functional result for dysphagia was excellent.
      Interesting results on fatigue and HRQoL must be interpreted with caution because
      of a limited patient material.

PMID- 30231807
TI  - Understandings of self-managed abortion as health inequity, harm reduction and
      social change.
AB  - This commentary explores how self-managed abortion (SMA) has transformed
      understandings of and discourses on safe abortion and associated health
      inequities through an intersection of harm reduction, human rights and collective
      activism. The article examines three primary understandings of the relationship
      between SMA and safe abortion: first SMA as health inequity, second SMA as harm
      reduction, and third SMA as social change, including health system innovation and
      reform. A more dynamic understanding of the relationship between SMA, safe
      abortion and health inequities can both improve the design of interventions in
      the field, and more radically reset reform goals for health systems and other
      state institutions towards the full realisation of sexual and reproductive health
      and human rights.

PMID- 30231808
TI  - Risk of intra-amniotic infection/inflammation and respiratory distress syndrome
      according to the birth order in twin preterm neonates.
AB  - OBJECTIVE: Prior studies have suggested that nonpresenting twins are more likely
      to develop respiratory distress syndrome (RDS) than presenting twins. While the
      underlying mechanism is not known, exposure to intra-amniotic
      infection/inflammation (IAI) has been associated with a reduced risk of RDS in
      singleton gestations. In the current study, we compared the risk of RDS in
      preterm twin neonates according to birth order with adjustment for the presence
      or absence of IAI. METHODS: The study population consisted of consecutive twin
      neonates who delivered <=35 weeks and underwent amniocentesis within 7 days of
      delivery. The frequency of RDS and IAI was compared between presenting and
      nonpresenting twin pairs. Amniotic fluid (AF) was cultured for aerobic/anaerobic
      bacteria and genital mycoplasma. IAI was defined as a positive AF culture or an
      AF white cell count >=19/mm3. RESULTS: A total of 120 twin pairs were enrolled.
      Compared with presenting twins, nonpresenting twins had a lower risk of IAI (36
      vs. 26%, respectively, p < .05), but a higher risk of RDS (18 vs. 25%,
      respectively, p < .05). In multivariate analysis, only IAI remained significantly
      associated with RDS (OR 0.18, 95% CI 0.05-0.65), whereas birth order was not.
      CONCLUSIONS: In preterm twin neonates, the increased risk of RDS in nonpresenting
      twins is likely due to lower exposure to IAI and not birth order.

PMID- 30231809
TI  - Liquid platelet-rich fibrin injections as a treatment adjunct for painful
      temporomandibular joints: preliminary results.
AB  - OBJECTIVE: To evaluate the clinical benefits of liquid platelet-rich fibrin (PRF)
      in patients with temporomandibular joint (TMJ) pain and dysfunction. METHODS:
      Forty-eight TMJs in 37 patients with painful internal derangement (ID) (Wilkes' I
      V) were included. Patients were injected with 1.5-2cc of PRF within the superior
      joint space at 2-week intervals. Pain and subjective dysfunction were recorded
      using a visual analog scale. Statistical analyses were done using the ANOVA test.
      RESULTS: Thirty-three of 48 TMJs (69%) showed significant reduction in pain at 8
      weeks, and at 3, 6, and 12 months (Responders). Fifteen of 48 TMJs (31%) did not
      improve (Non-responders). The best Responders to liquid PRF injections were ID
      stages Wilkes' IV (78.5%) and V (100%), compared to Wilkes' I (0%), II (47%), and
      III (33%). A non-significant, but notable decrease in dysfunction was found.
      CONCLUSION: Preliminary findings support that liquid PRF exhibits long-term
      analgesic effects in most patients with painful TMJ ID.

PMID- 30231810
TI  - Perspectives on Neuroscience and Behavior.

PMID- 30231813
TI  - Experience of Stress and Coping Strategies among Pastors' Wives in China.
AB  - A qualitative study was conducted to examine the experience of stress and coping
      strategies among 15 pastors' wives from a city in mainland China. Results
      indicated that nearly all interviewees experienced financial stress and
      loneliness, a phenomenon consistent with that seen in literature in the West.
      However, stress arising from role expectations among the spouses' congregations
      was low. Most interviewees coped with stress through family and social support,
      as well as through praying.

PMID- 30231814
TI  - Chronic Disease Prevention in Faith-Based Organizations.
AB  - According to the Centers for Disease Control and Prevention, currently one in two
      adults in the USA has a chronic disease and one in four has multiple chronic
      diseases. Many chronic diseases are largely preventable by engaging in an ongoing
      healthy lifestyle. This article provides (a) current rates of selected chronic
      diseases and their effects on individuals, (b) common modifiable risk factors for
      the diseases, and

PMID- 30231815
TI  - Medical Assistance in Dying: Challenges for Muslim Healthcare Professionals.
AB  - There appears to be a great deal of discussion among non-Muslim healthcare
      professionals, especially nurses and physicians, about medical assistance in
      dying. However, the discussion of medical assistance in dying among Muslim health
      caregivers including physicians, social workers, spiritual caregivers, etc.
      remains insufficient. A thorough analysis of the content of available resources
      revealed that we need more literature to analyze the attitude of Muslim health
      caregivers towards medical assistance in dying. This article describes the
      general attitude towards medical assistance in dying among non-Muslim. This will
      allow us to observe the challenges and dilemmas faced by Muslim healthcare
      professionals around medical assistance in dying.

PMID- 30231816
TI  - Assumptions about Frailty and the Tenacity of Ageism among Care Professionals.
AB  - Health, mental health, and pastoral care professionals encourage individuals to
      care for themselves in order to age successfully. Younger persons who live with
      long-term physical or mental health challenges are perceived as disabled or
      health-challenged. When older persons possess long-term physical or psychiatric
      challenges the older individual is perceived as frail or with deficits.
      Implications for clinical and pastoral care are considered as a result of
      perceptions of frailty in an ageist culture.

PMID- 30231817
TI  - Spiritual Care in a Social Media Landscape.
AB  - Given that social media extends both connection and suffering that occurs in
      physical spaces into digital spaces, issues of connection and suffering are
      increasingly integrated across people's online and in-person lives. Spiritual
      care in a new media landscape necessitates spiritual care practitioners who are
      invested in listening to, exploring, and ministering to people's social media
      experiences, both their joys and their laments.

PMID- 30231819
TI  - Personal Reflections on the Blame Game: The Game Everyone Loses.

PMID- 30231818
TI  - Are You Ready?
AB  - This is a reflection on being a chaplain. This reflection is an expression of the
      many emotional challenges I have encountered on any given day. This reflection
      could also be used to help new chaplains assimilate into the ministry.

PMID- 30231820
TI  - The Pastors.

PMID- 30231821
TI  - Where are You, God?

PMID- 30231822
TI  - Ministry to Transgender Teenagers (Part One): Pursuing Awareness and
      Understanding about Trans Youth.
AB  - Several significant aspects are addressed in this article to gain clarity and to
      pursue awareness regarding transgender teenagers. It begins by offering a brief
      introduction and then moves towards a common understanding of the language and
      landscape surrounding transgender teenagers. Next the paper centers on maligned,
      marginalized, and misunderstood transgender teenagers and the experiences they
      encounter. Hopefully, the information gleaned in this article will empower
      pastoral care givers to minister directly to this particular underserved sexual
      minority group.

PMID- 30231823
TI  - Reflection: A Supervisor's Journey through Middle Earth.
AB  - A brief metaphorical reflection on the work of supervision that draws on
      Tolkien's Lord of the Rings trilogy.

PMID- 30231825
TI  - The Journal of Pastoral Care & Counseling Quiz: (Continuing Education Quiz).

PMID- 30231824
TI  - Islam, The Holy Qur'an, and Medical Decision-Making: The Experience of Middle
      Eastern Muslim Families with Children Undergoing Bone Marrow Transplantation in
      the United States.
AB  - Some Arabic-speaking Muslim family members of children requiring bone marrow
      transplantation receive medical care for their children in the United States.
      Muslim family members' use of Islam in the course of their child's bone marrow
      transplantation was studied using grounded theory, a qualitative research method.
      Eighteen members of Middle Eastern Muslim families with a total of 13 children
      receiving bone marrow transplantation were interviewed by an Arabic-speaking
      healthcare provider. Interviews were coded by an interdisciplinary team. Seven
      key themes were identified.

PMID- 30231827
TI  - Words, Meanings, and Consequences.

PMID- 30231826
TI  - Integrating Pastoral and Clinical Identities: A Narrative Inquiry of Pastoral
      Counselors.
AB  - Narrative inquiry methodology was used to understand the lived experiences of two
      ordained pastoral counselors who obtained licensure as clinical mental health
      professionals, particularly in terms of their identity development and
      integration of pastoral and clinical identities. Data analysis from semi
      structured interviews revealed rich experiences with five themes: the journey;
      God's call; self and identity; the role of mentors; and relationships.
      Implications for research and practice associated with pastoral counseling and
      counselor education are discussed.

PMID- 30231829
TI  - Introduction.

PMID- 30231830
TI  - Demography of Living Arrangements Among Oldest-Old Mexican Americans: Evidence
      From the Hispanic Epidemiologic Study of the Elderly.
AB  - OBJECTIVE: In this article, we examine the demographics of living arrangements
      and household headship status among Mexican-origin individuals aged 85+ years.
      METHOD: Data come from the Hispanic Established Populations for the Epidemiologic
      Study of the Elderly (H-EPESE) caregiver and respondent surveys. RESULTS:
      Finances of the elderly individual and their caregiver inform living arrangement
      decisions. Physical and cognitive disability differentiate among living
      arrangements: The most mentally and physically impaired are most likely to live
      with others and less likely to be the head of the household. DISCUSSION:
      Motivations for living with others are clearly more complex than simple filial
      piety considerations might hold. Extended living arrangements provide concrete
      financial and instrumental benefits for both elderly parents and their adult
      child caregiver. Future research should address the question of the capacity of
      the Mexican American family to provide care for elderly parents in the face of
      major demographic and social changes.

PMID- 30231831
TI  - Impact of the Ebola epidemic on clinical outcomes of HIV-infected soldiers and
      their dependents in Sierra Leone.
AB  - The impact of the 2014-2016 Ebola epidemic in West Africa on human
      immunodeficiency virus (HIV) treatment in Sierra Leone is unknown, especially for
      groups with higher HIV prevalence such as the military. Using a retrospective
      study design, clinical outcomes were evaluated prior to and during the epidemic
      for 264 HIV-infected soldiers of the Republic of Sierra Leone Armed Forces
      (RSLAF) and their dependents receiving HIV treatment at the primary RSLAF HIV
      clinic. Medical records were abstracted for baseline clinical data and clinic
      attendance. Estimated risk of lost to follow-up (LTFU), default, and number of
      days without antiretroviral therapy (DWA) were calculated using repeated measures
      general estimating equations adjusted for age and gender. Due to missing data,
      262 patients were included in the final analyses. There was higher risk of LTFU
      throughout the Ebola epidemic in Sierra Leone compared to the pre-Ebola baseline,
      with the largest increase in LTFU risk occurring at the peak of the epidemic
      (relative risk: 3.22, 95% CI: 2.22-4.67). There was an increased risk of default
      and DWA during the Ebola epidemic for soldiers but not for their dependents. The
      risk of LTFU, default, and DWA stabilized once the epidemic was largely resolved
      but remained elevated compared to the pre-Ebola baseline. Our findings
      demonstrate the negative and potentially lasting impact of the Ebola epidemic on
      HIV care in Sierra Leone and highlight the need to develop strategies to minimize
      disruptions in HIV care with future disease outbreaks.

PMID- 30231832
TI  - HIV testing amongst older sexual health clinic attendees in England: an
      epidemiological study.
AB  - Older adults with HIV are at increased risk of late diagnosis. We aimed to
      explore the association between age and HIV testing rates in sexual health
      clinics in England using Public Health England data for 2009-2014. We
      investigated associations between attendee age and likelihood of HIV test offer,
      acceptance, and coverage. For each year, increasing age was associated with
      reduced likelihood of test offer (Rs -0.797 to -0.958, p < 0.01). Offer rates
      were highest for men who have sex with men (MSM), and lowest for heterosexual
      females (HSFs). HSFs had the greatest decline in offer rates with age (from 86.2%
      for age 25-29 to 52.1% for age 70+ in 2014). Odds ratios for test offer in 2014
      for attendees aged 15-49 compared with attendees aged 50+ were 1.94 (95%CI: 1.88,
      2.00) for heterosexual males (HSMs), 1.86 (95%CI: 1.81, 1.91) for HSFs, and 1.54
      (95%CI: 1.45, 1.64) for MSM. Overall, there was no significant association
      between age and test acceptance in any year (Rs -0.070 to -0.547; p > 0.05). The
      strongest determinant of acceptance was sexual orientation; for attendees aged
      50+, compared with HSMs, acceptance was higher for MSM (OR: 1.10; 95%CI: 1.06,
      1.13) and lower for HSFs (OR: 0.30; 95%CI: 0.30, 0.31).

PMID- 30231833
TI  - Do healthcare professionals and young adults know about the National Chlamydia
      Screening Programme? Findings from two cross-sectional surveys.
AB  - The extent to which healthcare professionals (HCPs) and young people (YP) are
      aware of, and adhere to, National Chlamydia Screening Programme (NCSP)
      recommendations on testing frequency is unclear. To address this two cross
      sectional surveys in 2015-2016: one among genitourinary medicine (GUM) and non
      GUM HCPs (n = 109) and the other among YP attending a GUM clinic in England (n =
      195). For both, questions were designed to measure awareness of NCSP guidance and
      whether respondents acted on that knowledge. This included questions about YP's
      most recent test(s) (if ever) and the time since first and last sex with their
      most recent partners. Knowledge of NCSP testing guidelines varied among both GUM
      and non-GUM HCP respondents. However, lack of knowledge of the guidelines did not
      preclude HCPs from recommending testing in line with NCSP recommendations in
      practice. While most YP were not aware of NCSP recommendations, around two-thirds
      had tested for Chlamydia at least once in the last year. However, testing seldom
      appeared to coincide with partnership change. There is a knowledge gap and a
      discord between testing recommendations and practice. Interventions are needed to
      encourage appropriate testing patterns to maximise the individual and public
      health benefits of testing.

PMID- 30231834
TI  - Crushed dolutegravir/abacavir/lamivudine given via nasogastric tube in gastric
      outlet obstruction caused by cancer resulted in rapid viral load suppression.
AB  - Alternative modes of antiretroviral administration are sought for people with
      impaired intestinal passage and/or absorption. We present a case of late HIV
      diagnosis (CD4+ count 160 cells/uL) with gastric outlet obstruction due to
      stomach adenocarcinoma. Co-morbidities included oesophageal candidiasis,
      Helicobacter pylori-positive duodenal ulcers and cytomegalovirus duodenitis. The
      gastric outlet obstruction required total parenteral nutrition and parenteral
      medication during four weeks of diagnostic work-up leading to pyloric resection.
      Crushed dolutegravir, abacavir and lamivudine were administered during this time
      in the evening via nasogastric tube, which was kept clamped overnight. The tube
      was unclamped in the morning and stomach content was drained during the daytime.
      This mode of administration resulted in rapid and sustained viral load
      suppression (from 300,000 to 115 copies per mL in 28 days, 81 copies/mL after 42
      days of treatment and less than 40 copies/mL thereafter). Therapeutic drug
      monitoring confirmed sufficient antiretroviral plasma levels during this mode of
      administration. The absorption of crushed dolutegravir, abacavir and lamivudine
      in the stomach may be considered in people with questionable gastrointestinal
      passage or impaired gastric emptying to achieve viral load suppression.

PMID- 30231835
TI  - Assessing the Unique Experiences and Needs of Muslim Oncology Patients Receiving
      Palliative and End-of-Life Care: An Integrative Review.
AB  - The objective of this review was to detail the experiences of Muslim oncology
      patients receiving palliative and end-of-life care and identify where gaps in the
      providing of culturally aware care occur. We also sought to examine ways in which
      providers could be better educated on the needs of Muslim patients at the end-of
      life and identify barriers Muslims faced when being treated with hospice and
      palliative care models developed for non-Muslim populations. We conducted a
      search in April 2018 in the National Library of Medicine and CINAHL databases
      using the search terms "palliative care," "Muslim," and "cancer." Included were
      articles with focuses on adult Muslims with palliative and end-of-life care
      experiences. We then followed the PRISMA guidelines for an integrative review and
      used a data extraction matrix to identify 20 papers that met the inclusion
      criteria of the review. We identified four major themes patient experiences,
      patient care delivery suggestions, Muslim provider experiences, and definitions
      of death, present in all 20 papers of the review. Each of the included papers was
      categorized based on the dominant theme in the paper. This review ultimately
      found that the care provided to Muslim patients is subpar for the standard of
      culturally competent care and that the needs of Muslim patients at the end-of
      life, as well as the needs of their families, are not being met. Moving forward
      further research on this topic is needed with a particular focus on examining the
      experiences of terminally ill Muslim patients receiving treatment in non-Muslim
      majority settings.

PMID- 30231838
TI  - Perspectives on Neuroscience and Behavior.

PMID- 30231839
TI  - Perspectives on Neuroscience and Behavior.

PMID- 30231842
TI  - Working Memory: How Important Is White Matter?
AB  - Working memory, the ability to transiently keep, process, and use information as
      part of ongoing mental processes is an essential feature of cognitive
      functioning. The largest number of items that people can hold in their working
      memory, referred to as the capacity of working memory, is limited and varies
      substantially among individuals. Uncovering the biological factors that underlie
      these two defining properties of working memory capacity remains a key
      undertaking of modern cognitive neuroscience since capacity strongly predicts how
      well we reason, learn, and even do math. In this work we review data that
      highlights the role white matter, which provides the wiring of the extensive
      neural networks that activate during working memory tasks, may play in
      interindividual variations in capacity. We also describe advanced diffusion
      imaging methods, which may be uniquely suited in capturing those white matter
      features that are most relevant to capacity. Finally, we discuss several possible
      mechanisms through which white matter may both contribute to and limit working
      memory.

PMID- 30231843
TI  - Perception of Affordances for Stepping Over an Expanse With Crutches.
AB  - Perception of possibilities for behavior reflects the task-specific fit between
      action capabilities and environmental properties. We investigated whether this is
      so for a behavior that requires spontaneously and temporarily coordinating
      anatomical components and inert objects into a person-plus-object action system
      stepping over an expanse with crutches. We found that perception of this
      affordance (a) scaled to an anthropometric property of primary relevance to
      performing this behavior (leg length), (b) reflected the ability to perform this
      behavior, and that (c) variability in perception decreased with practice
      perceiving this affordance. The results are consistent with the proposal that
      perceiving affordances for a given behavior requires assembling a task-specific
      perceptual instrument.

PMID- 30231846
TI  - Marine debris, plastics, microplastics and nano-plastics: What next?

PMID- 30231848
TI  - Perspectives on Neuroscience and Behavior.

PMID- 30231844
TI  - Anxiety Body Odors as Context for Dynamic Faces: Categorization and
      Psychophysiological Biases.
AB  - Body odors (BOs) can convey social information. In particular, their effects are
      maximal when their presence is paired with meaningful social contexts. Static
      faces have been widely used as social stimuli. However, they miss a key feature
      of our phenomenological experience, characterized by multisensory dynamic
      stimulations. Here, we investigate how BO sampled from individuals experiencing a
      transitory anxiety state, (a) induce a stress response and (b) bias the
      recognition of dynamic facial expressions, compared with BO of relaxed
      individuals. Participants ( n=46) categorized the emotion of a face, morphing
      from a neutral expression to either an angry or happy expression, during exposure
      to either BO condition. In addition, their cardiac activity was measured.
      Exposure to anxiety BO increased the accuracy of dynamic facial recognition and
      reduced cardiac parasympathetic activity. These results suggest that in social
      situations that simulate part of the multisensory and dynamic features of real
      life social contexts, anxiety BOs will induce a stress response in recipients,
      modulating both arousal and cognitive-emotional skills but facilitating emotional
      facial processing.

PMID- 30231850
TI  - Exome scale map of genetic alterations promoting metastasis in colorectal cancer.
AB  - BACKGROUND: Approximately 90% of colorectal cancer (CRC) deaths are caused by
      tumors ability to migrate into the adjacent tissues and metastase into distant
      organs. More than 40 genes have been causally linked to the development of CRC
      but no mutations have been associated with metastasis yet. To identify molecular
      basis of CRC metastasis we performed whole-exome and genome-scale transcriptome
      sequencing of 7 liver metastases along with their matched primary tumours and
      normal tissue. Multiple, spatially separated fragments of primary tumours were
      analyzed in each case. Uniformly malignant tissue specimen were selected with
      macrodissection, for three samples followed with laser microdissection. RESULTS:
      > 100 sequencing coverage allowed for detection of genetic alterations in
      subpopulation of tumour cells. Mutations in KRAS, APC, POLE, and PTPRT,
      previously associated with CRC development, were detected in most patients.
      Several new associations were identified, including PLXND1, CELSR3, BAHD1 and
      PNPLA6. CONCLUSIONS: We confirm the essential role of inflammation in CRC
      progression but question the mechanism of matrix metalloproteinases activation
      described in other work. Comprehensive sequencing data made it possible to
      associate genome-scale mutation distribution with gene expression patterns. To
      our knowledge, this is the first work to report such link in CRC metastasis
      context.

PMID- 30231851
TI  - Onset and progression of diabetes in kidney transplant patients receiving
      everolimus or cyclosporine therapy: an analysis of two randomized, multicenter
      trials.
AB  - BACKGROUND: Conversion from calcineurin inhibitor (CNI) therapy to a mammalian
      target of rapamycin (mTOR) inhibitor following kidney transplantation may help to
      preserve graft function. Data are sparse, however, concerning the impact of
      conversion on posttransplant diabetes mellitus (PTDM) or the progression of pre
      existing diabetes. METHODS: PTDM and other diabetes-related parameters were
      assessed post hoc in two large open-label multicenter trials. Kidney transplant
      recipients were randomized (i) at month 4.5 to switch to everolimus or remain on
      a standard cyclosporine (CsA)-based regimen (ZEUS, n = 300), or (ii) at month 3
      to switch to everolimus, remain on standard CNI therapy or convert to everolimus
      with reduced-exposure CsA (HERAKLES, n = 497). RESULTS: There were no significant
      differences in the incidence of PTDM between treatment groups (log rank p = 0.97
      [ZEUS], p = 0.90 [HERAKLES]). The mean change in random blood glucose from
      randomization to month 12 was also similar between treatment groups in both
      trials for patients with or without PTDM, and with or without pre-existing
      diabetes. The change in eGFR from randomization to month 12 showed a benefit for
      everolimus versus comparator groups in all subpopulations, but only reached
      significance in larger subgroups (no PTDM or no pre-existing diabetes).
      CONCLUSIONS: Within the restrictions of this post hoc analysis, including non
      standardized diagnostic criteria and limited glycemia laboratory parameters,
      these data do not indicate any difference in the incidence or severity of PTDM
      with early conversion from a CsA-based regimen to everolimus, or in the
      progression of pre-existing diabetes. TRIAL REGISTRATION: clinicaltrials.gov ,
      NCT00154310 (registered September 2005) and NCT00514514 (registered August 2007);
      EudraCT ( 2006-007021-32 and 2004-004346-40 ).

PMID- 30231852
TI  - Atypical sensory processing pattern following median or ulnar nerve injury - a
      case-control study.
AB  - BACKGROUND: Due to brain plasticity a transection of a median or ulnar nerve
      results in profound changes in the somatosensory areas in the brain. The
      permanent sensory deprivation after a peripheral nerve injury might influence the
      interaction between all senses. The aim of the study was to investigate if a
      median and/or ulnar nerve injury gives rise to a changed sensory processing
      pattern. In addition we examined if age at injury, injured nerve or time since
      injury influence the sensory processing pattern. METHODS: Fifty patients (40 men
      and 10 women, median age 43) operated due to a median and/or ulnar nerve injury
      were included. The patients completed the Adolescent/Adult Sensory Profile
      questionnaire, which includes a comprehensive characterization on how sensory
      information is processed and how an individual responds to multiple sensory
      modalities. AASP categorizes the results into four possible Quadrants of
      behavioral profiles (Q1-low registration, Q2-sensory seeking, Q3-sensory
      sensitivity and Q4-sensory avoiding). The results were compared to 209 healthy
      age and gender matched controls. Anova Matched Design was used for evaluation of
      differences between the patient group and the control group. Atypical sensory
      processing behavior was determined in relation to the normative distribution of
      the control group. RESULTS: Significant difference was seen in Q1, low
      registration. 40% in the patient group scored atypically in this Quadrant
      compared to 16% of the controls. No correlation between atypical sensory
      processing pattern and age or time since injury was seen. CONCLUSION: A
      peripheral nerve injury entails altered sensory processing pattern with increased
      proportion of patients with low registration to sensory stimulus overall. Our
      results can guide us into more client centered rehabilitation strategies.

PMID- 30231853
TI  - AgriSeqDB: an online RNA-Seq database for functional studies of agriculturally
      relevant plant species.
AB  - BACKGROUND: The genome-wide expression profile of genes in different tissues/cell
      types and developmental stages is a vital component of many functional genomic
      studies. Transcriptome data obtained by RNA-sequencing (RNA-Seq) is often
      deposited in public databases that are made available via data portals. Data
      visualization is one of the first steps in assessment and hypothesis generation.
      However, these databases do not typically include visualization tools and
      establishing one is not trivial for users who are not computational experts.
      This, as well as the various formats in which data is commonly deposited, makes
      the processes of data access, sharing and utility more difficult. Our goal was to
      provide a simple and user-friendly repository that meets these needs for data
      sets from major agricultural crops. DESCRIPTION: AgriSeqDB (
      https://expression.latrobe.edu.au/agriseqdb ) is a database for viewing,
      analysing and interpreting developmental and tissue/cell-specific transcriptome
      data from several species, including major agricultural crops such as wheat,
      rice, maize, barley and tomato. The disparate manner in which public
      transcriptome data is often warehoused and the challenge of visualizing raw data
      are both major hurdles to data reuse. The popular eFP browser does an excellent
      job of presenting transcriptome data in an easily interpretable view, but
      previous implementation has been mostly on a case-by-case basis. Here we present
      an integrated visualisation database of transcriptome data-sets from six species
      that did not previously have public-facing visualisations. We combine the eFP
      browser, for gene-by-gene investigation, with the Degust browser, which enables
      visualisation of all transcripts across multiple samples. The two visualisation
      interfaces launch from the same point, enabling users to easily switch between
      analysis modes. The tools allow users, even those without bioinformatics
      expertise, to mine into data-sets and understand the behaviour of transcripts of
      interest across samples and time. We have also incorporated an additional graphic
      download option to simplify incorporation into presentations or publications.
      CONCLUSION: Powered by eFP and Degust browsers, AgriSeqDB is a quick and easy-to
      use platform for data analysis and visualization in five crops and Arabidopsis.
      Furthermore, it provides a tool that makes it easy for researchers to share their
      data-sets, promoting research collaborations and data-set reuse.

PMID- 30231854
TI  - Predicting treatment Response based on Dual assessment of magnetic resonance
      Imaging kinetics and Circulating Tumor cells in patients with Head and Neck
      cancer (PREDICT-HN): matching 'liquid biopsy' and quantitative tumor modeling.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has improved capacity to visualize
      tumor and soft tissue involvement in head and neck cancers. Using advanced MRI,
      we can interrogate cell density using diffusion weighted imaging, a quantitative
      imaging that can be used during radiotherapy, when diffuse inflammatory reaction
      precludes PET imaging, and can assist with target delineation as well.
      Correlation of circulating tumor cells (CTCs) measurements with 3D quantitative
      tumor characterization could potentially allow selective, patient-specific
      response-adapted escalation or de-escalation of local therapy, and improve the
      therapeutic ratio, curing the greatest number of patients with the least
      toxicity. METHODS: The proposed study is designed as a prospective observational
      study and will collect pretreatment CT, MRI and PET/CT images, weekly serial MR
      imaging during RT and post treatment CT, MRI and PET/CT images. In addition,
      blood sample will be collected for biomarker analysis at those time intervals.
      CTC assessments will be performed on the CellSave tube using the FDA-approved
      CellSearch(r) Circulating Tumor Cell Kit (Janssen Diagnostics), and plasma from
      the EDTA blood samples will be collected, labeled with a de-identifying number,
      and stored at - 80  degrees C for future analyses. DISCUSSION: The primary
      objective of the study is to evaluate the prognostic value and correlation of
      weekly tumor response kinetics (gross tumor volume and MR signal changes) and
      circulating tumor cells of mucosal head and neck cancers during radiation therapy
      using MRI in predicting treatment response and clinical outcomes. This study will
      provide landmark information as to the utility of CTCs ('liquid biopsy) and tumor
      specific functional quantitative imaging changes during treatment to guide
      personalization of treatment for future patients. Combining the biological
      information from CTCs and the structural information from MRI may provide more
      information than either modality alone. In addition, this study could potentially
      allow us to determine the optimal time to obtain MR imaging and/ or CTCs during
      radiotherapy to assess tumor response and provide guidance for patient selection
      and stratification for future dose escalation or de-escalation strategies. TRIAL
      REGISTRATION: Clinicaltrials.gov ( NCT03491176 ). Date of registration: 9th April
      2018. (retrospectively registered). Date of enrolment of the first participant:
      30th May 2017.

PMID- 30231855
TI  - Bacterial endosymbiont Cardinium cSfur genome sequence provides insights for
      understanding the symbiotic relationship in Sogatella furcifera host.
AB  - BACKGROUND: Sogatella furcifera is a migratory pest that damages rice plants and
      causes severe economic losses. Due to its ability to annually migrate long
      distances, S. furcifera has emerged as a major pest of rice in several Asian
      countries. Symbiotic relationships of inherited bacteria with terrestrial
      arthropods have significant implications. The genus Cardinium is present in many
      types of arthropods, where it influences some host characteristics. We present a
      report of a newly identified strain of the bacterial endosymbiont Cardinium cSfur
      in S. furcifera. RESULT: From the whole genome of S. furcifera previously
      sequenced by our laboratory, we assembled the whole genome sequence of Cardinium
      cSfur. The sequence comprised 1,103,593 bp with a GC content of 39.2%. The
      phylogenetic tree of the Bacteroides phylum to which Cardinium cSfur belongs
      suggests that Cardinium cSfur is closely related to the other strains (Cardinium
      cBtQ1 and cEper1) that are members of the Amoebophilaceae family. Genome
      comparison between the host-dependent endosymbiont including Cardinium cSfur and
      free-living bacteria revealed that the endosymbiont has a smaller genome size and
      lower GC content, and has lost some genes related to metabolism because of its
      special environment, which is similar to the genome pattern observed in other
      insect symbionts. Cardinium cSfur has limited metabolic capability, which makes
      it less contributive to metabolic and biosynthetic processes in its host. From
      our findings, we inferred that, to compensate for its limited metabolic
      capability, Cardinium cSfur harbors a relatively high proportion of transport
      proteins, which might act as the hub between it and its host. With its
      acquisition of the whole operon related to biotin synthesis and glycolysis
      related genes through HGT event, Cardinium cSfur seems to be undergoing changes
      while establishing a symbiotic relationship with its host. CONCLUSION: A novel
      bacterial endosymbiont strain (Cardinium cSfur) has been discovered. A genomic
      analysis of the endosymbiont in S. furcifera suggests that its genome has
      undergone certain changes to facilitate its settlement in the host. The envisaged
      potential reproduction manipulative ability of the new endosymbiont strain in its
      S. furcifera host has vital implications in designing eco-friendly approaches to
      combat the insect pest.

PMID- 30231856
TI  - Transcriptome dynamics of rooting zone and aboveground parts of cuttings during
      adventitious root formation in Cryptomeria japonica D. Don.
AB  - BACKGROUND: Adventitious root formation is an essential physiological process for
      successful propagation of cuttings in various plant species. Because coniferous
      species are highly heterozygous, propagation of cuttings is of great practical
      use in breeding. Although various factors influence adventitious root formation,
      little is known of the associated regulatory mechanisms. Whereas adventitious
      roots generally form from the base of cuttings, this process is accompanied by
      physiological changes in leaves, which supply assimilates and metabolites.
      Herein, we present microarray analyses of transcriptome dynamics during
      adventitious root formation in whole cuttings in the coniferous species,
      Cryptomeria japonica. RESULTS: Temporal patterns of gene expression were
      determined in the base, the middle, and needles of cuttings at eight time points
      during adventitious root formation. Global gene expression at the base had
      diverged from that in the middle by 3-h post-insertion, and changed little in the
      subsequent 3-days post-insertion, and global gene expression in needles altered
      characteristically at 3- and 6-weeks post-insertion. In Gene Ontology enrichment
      analysis of major gene clusters based on hierarchical clustering, the expression
      profiles of genes related to carbohydrates, plant hormones, and other categories
      indicated multiple biological changes that were involved in adventitious root
      formation. CONCLUSIONS: The present comprehensive transcriptome analyses indicate
      major transcriptional turning and contribute to the understanding of the
      biological processes and molecular factors that influence adventitious root
      formation in C. japonica.

PMID- 30231857
TI  - Epidemiological characteristics and influential factors of hand, foot, and mouth
      disease reinfection in Wuxi, China, 2008-2016.
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) is a viral disease caused by
      human enteroviruses. Although HFMD reinfection is common, studies investigating
      this phenomenon are insufficient. METHODS: The present study focused on HFMD
      reinfection in Wuxi from 2008 to 2016 using surveillance system data. RESULTS: Of
      107,677 cases included in the study, 6470 cases were classified as reinfections.
      The overall reinfection rate was 6.01% (6.37% male and 5.48% female patients),
      which decreased with increasing age (chi2 = 1125.477, p < 0.001). The rate was
      6.17 and 5.79% in urban and rural areas, respectively, and 7.83 and 5.98% of the
      cases were severe and mild, respectively. Multivariate logistic regression
      analysis showed that male sex, younger age, residence in an urban area, and
      severe disease were risk factors for HFMD reinfection. The case-severity rate in
      secondary infection cases was lower than that in non-reinfection cases (odds
      ratio 0.675, 95% confidence interval 0.526-0.866). CONCLUSIONS: Boys younger than
      4 years of age living in urban areas were more prone to reinfection. Specific
      health education and intervention should be developed to protect these
      susceptible populations.

PMID- 30231858
TI  - Activation of RAAS in a rat model of liver cirrhosis: no effect of losartan on
      renal sodium excretion.
AB  - BACKGROUND: Liver cirrhosis is characterized by avid sodium retention where the
      activation of the renin angiotensin aldosterone system (RAAS) is considered to be
      the hallmark of the sodium retaining mechanisms. The direct effect of angiotensin
      II (ANGII) on the AT-1 receptor in the proximal tubules is partly responsible for
      the sodium retention. The aim was to estimate the natriuretic and neurohumoral
      effects of an ANGII receptor antagonist (losartan) in the late phase of the
      disease in a rat model of liver cirrhosis. METHODS: Bile duct ligated (BDL) and
      sham operated rats received 2 weeks of treatment with losartan 4 mg/kg/day or
      placebo, given by gastric gavage 5 weeks after surgery. Daily sodium and
      potassium intakes and renal excretions were measured. RESULTS: The renal sodium
      excretion decreased in the BDL animals and this was not affected by losartan
      treatment. At baseline the plasma renin concentration (PRC) was similar in sham
      and BDL animals, but increased urinary excretion of ANGII and an increase P
      Aldosterone was observed in the placebo treated BDL animals. The PRC was more
      than 150 times higher in the losartan treated BDL animals (p < 0.001) which
      indicated hemodynamic impairment. CONCLUSIONS: Losartan 4 mg/kg/day did not
      increase renal sodium excretion in this model of liver cirrhosis, although the
      urinary ANGII excretion was increased. The BDL animals tolerated Losartan poorly,
      and the treatment induced a 150 times higher PRC.

PMID- 30231859
TI  - Pancreas grafts for transplantation from donors with hypertension: an analysis of
      the scientific registry of transplant recipients database.
AB  - BACKGROUND: With the rising demands for pancreas transplantation, surgeons are
      trying to extend the donors pool and set up a more appropriate assessment system.
      We aim to evaluate the effect of donor hypertension on recipient overall and
      graft survival rates. METHODS: Twenty-four thousand one hundred ninety-two
      pancreas transplantation patients from the Scientific Registry of Transplant
      Recipients database were subdivided into hypertension group (HTN, n = 1531) and
      non-hypertension group (non-HTN, n = 22,661) according to the hypertension status
      of donors. Recipient overall and graft survival were analyzed and compared by log
      rank test, and hazard ratios of predictors were estimated using Cox proportional
      hazard models. RESULTS: Patient overall and graft survival of non-HTN group were
      higher than that of the HTN group (both p < 0.001). The duration of hypertension
      negatively influenced both overall and graft survival rates (both p < 0.001).
      Multivariate analyses demonstrated that hypertension was an independent factor
      for reduced survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.01
      1.18; p < 0.001). Other independent factors included recipient body mass index
      (HR, 1.02; 95% CI, 1.01-1.05; p < 0.001) and transplant type (pancreas after
      kidney transplants / pancreas transplant alone vs. simultaneous pancreas-kidney
      transplants; HR, 1.41; 95% CI, 134-1.55; p < 0.001). CONCLUSIONS: Donor
      hypertension is an independent factor for recipient survival after pancreas
      transplantation and could be considered in donor selection as well as post
      transplant surveillance in clinical practice.

PMID- 30231861
TI  - Transcranial focused ultrasound stimulation of motor cortical areas in freely
      moving awake rats.
AB  - BACKGROUND: Low-intensity transcranial focused ultrasound (tFUS) has emerged as a
      new non-invasive modality of brain stimulation with the potential for high
      spatial selectivity and penetration depth. Anesthesia is typically applied in
      animal-based tFUS brain stimulation models; however, the type and depth of
      anesthesia are known to introduce variability in responsiveness to the
      stimulation. Therefore, the ability to conduct sonication experiments on awake
      small animals, such as rats, is warranted to avoid confounding effects of
      anesthesia. RESULTS: We developed a miniature tFUS headgear, operating at 600
      kHz, which can be attached to the skull of Sprague-Dawley rats through an
      implanted pedestal, allowing the ultrasound to be transcranially delivered to
      motor cortical areas of unanesthetized freely-moving rats. Video recordings were
      obtained to monitor physical responses from the rat during acoustic brain
      stimulation. The stimulation elicited body movements from various areas, such as
      the tail, limbs, and whiskers. Movement of the head, including chewing behavior,
      was also observed. When compared to the light ketamine/xylazine and isoflurane
      anesthetic conditions, the response rate increased while the latency to
      stimulation decreased in the awake condition. The individual variability in
      response rates was smaller during the awake condition compared to the anesthetic
      conditions. Our analysis of latency distribution of responses also suggested
      possible presence of acoustic startle responses mixed with stimulation-related
      physical movement. Post-tFUS monitoring of animal behaviors and histological
      analysis performed on the brain did not reveal any abnormalities after the
      repeated tFUS sessions. CONCLUSIONS: The wearable miniature tFUS configuration
      allowed for the stimulation of motor cortical areas in rats and elicited
      sonication-related movements under both awake and anesthetized conditions. The
      awake condition yielded diverse physical responses compared to those reported in
      existing literatures. The ability to conduct an experiment in freely-moving awake
      animals can be gainfully used to investigate the effects of acoustic
      neuromodulation free from the confounding effects of anesthesia, thus, may serve
      as a translational platform to large animals and humans.

PMID- 30231863
TI  - Epidemiological and clinical profiles of acute poisoning in patients admitted to
      the intensive care unit in eastern Iran (2010 to 2017).
AB  - BACKGROUND: Acute poisoning is a common chief complaint leading to emergency
      department visits and hospital admissions in developing countries such as Iran.
      Data describing the epidemiology of different poisonings, characteristics of the
      clinical presentations, and the predictors of outcome are lacking. Such data can
      help develop more efficient preventative and management strategies to decrease
      morbidity and mortality related to these poisonings. This manuscript describes
      the epidemiology of acute poisoning among patients admitted to the intensive care
      unit (ICU) in Birjand, Iran. METHODS: This retrospective, cross-sectional study
      was conducted to characterize acute poisonings managed in the ICU during a 7-year
      period from March 2010 to March 2017 in a single center in Birjand, Iran. Patient
      characteristics, suspected exposure, the route of exposure, and outcome data were
      collected from hospital medical records. RESULTS: During the study period, 267
      (64% male and 36% female) patients met inclusion criteria. Pharmaceutical
      medication (36.6%), opioids (26.2%) followed by pesticides (13.9%) were the most
      common exposures 38.2% of these cases were identified as suicide attempts. There
      were different frequencies in terms of xenobiotic exposure in relation to gender
      (p = 0.04) and the survival (p = 0.001). There was a significant difference
      between various xenobiotics identified as the cause of poisoning (p = 0.001).
      Mortality rate in our study was 19.5%. The incidence of outcomes was
      significantly higher in patients poisoned with opioids, pesticides,
      benzodiazepines, and tricyclic antidepressants (p < 0.05). The median length of
      hospital stay was higher in pesticide-poisoned patients (p = 0.04). CONCLUSION:
      Opioids and pesticides were the most common exposures. The mortality rate of the
      poisoned patients in the ICU was proportionately high. The mortality rate due to
      opioid poisoning is a major concern and the most significant cause death due to
      poisoning in the region. Further monitoring and characterization of acute
      poisoning in Birjand, Iran is needed. These data can help develop educational and
      preventative programs to reduce these exposures and improve management of
      exposures in the prehospital and hospital settings.

PMID- 30231860
TI  - Inadequate dietary energy intake associates with higher prevalence of metabolic
      syndrome in different groups of hemodialysis patients: a clinical observational
      study in multiple dialysis centers.
AB  - BACKGROUND: Metabolic syndrome (MetS) has been established as a risk for
      cardiovascular diseases and mortality in hemodialysis patients. Energy intake
      (EI) is an important nutritional therapy for preventing MetS. We examined the
      association of self-reported dietary EI with metabolic abnormalities and MetS
      among hemodialysis patients. METHODS: A cross-sectional study design was carried
      out from September 2013 to April 2017 in seven hemodialysis centers. Data were
      collected from 228 hemodialysis patients with acceptable EI report, 20 years old
      and above, underwent three hemodialysis sessions a week for at least past 3
      months. Dietary EI was evaluated by a three-day dietary record, and confirmed by
      24-h dietary recall. Body compositions were measured by bioelectrical impedance
      analysis. Biochemical data were analyzed using standard laboratory tests. The cut
      off values of daily EI were 30 kcal/kg, and 35 kcal/kg for age >= 60 years and <
      60 years, respectively. MetS was defined by the American Association of Clinical
      Endocrinologists (AACE-MetS), and Harmonizing Metabolic Syndrome (HMetS).
      Logistic regression models were utilized for examining the association between EI
      and MetS. Age, gender, physical activity, hemodialysis vintage, Charlson
      comorbidity index, high sensitive C-reactive protein, and interdialytic weight
      gains were adjusted in the multivariate analysis. RESULTS: The prevalence of
      inadequate EI, AACE-MetS, and HMetS were 60.5%, 63.2%, and 53.9%, respectively.
      Inadequate EI was related to higher proportion of metabolic abnormalities and
      MetS (p <  0.05). Results of the multivariate analysis shows that inadequate EI
      was significantly linked with higher prevalence of impaired fasting glucose (OR =
      2.42, p <  0.01), overweight/obese (OR = 6.70, p <  0.001), elevated waist
      circumference (OR = 8.17, p <  0.001), AACE-MetS (OR = 2.26, p <  0.01), and
      HMetS (OR = 3.52, p <  0.01). In subgroup anslysis, inadequate EI strongly
      associated with AACE-MetS in groups of non-hypertension (OR = 4.09, p = 0.004),
      and non-cardiovascular diseases (OR = 2.59, p = 0.012), and with HMetS in all sub
      groups of hypertension (OR = 2.59~ 5.33, p <  0.05), diabetic group (OR = 8.33, p
      = 0.003), and non-cardiovascular diseases (OR = 3.79, p <  0.001). CONCLUSIONS:
      Inadequate EI and MetS prevalence was high. Energy intake strongly determined
      MetS in different groups of hemodialysis patients.

PMID- 30231862
TI  - Exploring transcription factors reveals crucial members and regulatory networks
      involved in different abiotic stresses in Brassica napus L.
AB  - BACKGROUND: Brassica napus (B. napus) encompasses diverse transcription factors
      (TFs), but thorough identification and characterization of TF families, as well
      as their transcriptional responsiveness to multifarious stresses are still not
      clear. RESULTS: Totally 2167 TFs belonging to five families were genome-widely
      identified in B. napus, including 518 BnAP2/EREBPs, 252 BnbZIPs, 721 BnMYBs, 398
      BnNACs and 278 BnWRKYs, which contained some novel members in comparison with
      existing results. Sub-genome distributions of BnAP2/EREBPs and BnMYBs indicated
      that the two families might have suffered from duplication and divergence during
      evolution. Synteny analysis revealed strong co-linearity between B. napus and its
      two ancestors, although chromosomal rearrangements have occurred and 85 TFs were
      lost. About 7.6% and 9.4% TFs of the five families in B. napus were novel genes
      and conserved genes, which both showed preference on the C sub-genome. RNA-Seq
      revealed that more than 80% TFs were abiotic stress inducible and 315 crucial
      differentially expressed genes (DEGs) were screened out. Network analysis
      revealed that the 315 DEGs are highly co-expressed. The homologous gene network
      in A. thaliana revealed that a considerable amount of TFs could trigger the
      differential expression of targeted genes, resulting in a complex clustered
      network with clusters of genes responsible for targeted stress responsiveness.
      CONCLUSIONS: We identified and characterized five TF families in B. napus. Some
      crucial members and regulatory networks involved in different abiotic stresses
      have been explored. The investigations deepen our understanding of TFs for stress
      tolerance in B. napus.

PMID- 30231865
TI  - The survivability of dialectical behaviour therapy programmes: a mixed methods
      analysis of barriers and facilitators to implementation within UK healthcare
      settings.
AB  - BACKGROUND: Dialectical Behaviour Therapy (DBT) is an evidence-based intervention
      that has been included in the National Institute of Health and Care Excellence
      guidelines as a recommended treatment for Borderline Personality Disorder in the
      UK. However, implementing and sustaining evidence-based treatments in routine
      practice can be difficult to achieve. This study compared the survival of early
      and late adopters of DBT as well as teams trained via different training modes
      (on-site versus off-site), and explored factors that aided or hindered
      implementation of DBT into routine healthcare settings. METHODS: A mixed-method
      approach was used. Kaplan-Meier survival analyses were conducted to quantify and
      compare survivability as a measure of sustainability between early and late
      implementers and those trained on- and off-site. An online questionnaire based on
      the Consolidated Framework for Implementation Research was used to explore
      barriers and facilitators in implementation. A quantitative content analysis of
      survey responses was carried out. RESULTS: Early implementers were significantly
      less likely to survive than late implementers, although, the effect size was
      small. DBT teams trained off-site were significantly more likely to survive. The
      effect size for this difference was large.  An unequal amount of censored data
      between groups in both analyses means that findings should be considered
      tentative. Practitioner turnover and financing were the most frequently cited
      barriers to implementation. Individual characteristics of practitioners and
      quality of the evidence base were the most commonly reported facilitators to
      implementation. CONCLUSIONS: A number of common barriers and facilitators to
      successful implementation of DBT were found among DBT programmes. Location of DBT
      training may mediate programme survival.

PMID- 30231864
TI  - Microhabitat change drives diversification in pholcid spiders.
AB  - BACKGROUND: Microhabitat changes are thought to be among the main drivers of
      diversification. However, this conclusion is mostly based on studies on
      vertebrates. Here, we investigate the influence of microhabitat on
      diversification rates in pholcid spiders (Araneae, Pholcidae). Diversification
      analyses were conducted in the framework of the largest molecular phylogeny of
      pholcid spiders to date based on three nuclear and three mitochondrial loci from
      600 species representing more than 85% of the currently described pholcid genera.
      RESULTS: Assessments of ancestral microhabitat revealed frequent evolutionary
      change. In particular, within the largest subfamily Pholcinae, numerous changes
      from near-ground habitats towards leaves and back were found. In general, taxa
      occupying leaves and large sheltered spaces had higher diversification rates than
      ground-dwelling taxa. Shifts in speciation rate were found in leaf- and space
      dwelling taxa. CONCLUSIONS: Our analyses result in one of the most comprehensive
      phylogenies available for a major spider family and provide a framework for any
      subsequent studies of pholcid spider biology. Diversification analyses strongly
      suggest that microhabitat is an important factor influencing diversification
      patterns in pholcid spiders.

PMID- 30231867
TI  - Correction to: Associations between post-operative rehabilitation of hip fracture
      and outcomes: national database analysis.
AB  - Following publication of the original article [1], the author reported an error
      in the Title. The original article has been corrected.

PMID- 30231866
TI  - Study protocol: a randomised controlled trial on the clinical effects of
      levothyroxine treatment for subclinical hypothyroidism in people aged 80 years
      and over.
AB  - BACKGROUND: Subclinical hypothyroidism is common in older people and its
      contribution to health and disease needs to be elucidated further. Observational
      and clinical trial data on the clinical effects of subclinical hypothyroidism in
      persons aged 80 years and over is inconclusive, with some studies suggesting harm
      and some suggesting benefits, translating into equipoise whether levothyroxine
      therapy provides clinical benefits. This manuscript describes the study protocol
      for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid
      trial to generate the necessary evidence base. METHODS: The IEMO 80-plus thyroid
      trial was explicitly designed as an ancillary experiment to the Thyroid hormone
      Replacement for Untreated older adults with Subclinical hypothyroidism randomised
      placebo controlled Trial (TRUST) with a near identical protocol and shared
      research infrastructure. Outcomes will be presented separately for the IEMO and
      TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145
      participants included in the IEMO trial and the 146 participants from the TRUST
      thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi
      centre randomised double-blind placebo-controlled parallel group trial of
      levothyroxine treatment in community-dwelling participants aged 80 years and over
      with persistent subclinical hypothyroidism (TSH >=4.6 and <= 19.9 mU/L and fT4
      within laboratory reference ranges). Participants are randomised to levothyroxine
      25 or 50 micrograms daily or matching placebo with dose titrations according to
      TSH levels, for a minimum follow-up of one and a maximum of three years. Primary
      study endpoints: hypothyroid physical symptoms and tiredness on the thyroid
      related quality of life patient-reported outcome (ThyPRO) at one year. Secondary
      endpoints: generic quality of life, executive cognitive function, handgrip
      strength, functional ability, blood pressure, weight, body mass index, and
      mortality. Adverse events will be recorded with specific interest on
      cardiovascular endpoints such as atrial fibrillation and heart failure.
      DISCUSSION: The combined analysis of participants in the IEMO 80-plus thyroid
      trial with the participants aged over 80 in the TRUST trial will provide the
      largest experimental evidence base on multimodal effects of levothyroxine
      treatment in 80-plus persons to date. TRIAL REGISTRATION: Nederlands (Dutch)
      Trial Register: NTR3851 (12-02-2013), EudraCT: 2012-004160-22 (17-02-2013), ABR
      41259.058.13 (12-02-2013).

PMID- 30231868
TI  - Evolution in chronic cold: varied loss of cellular response to heat in Antarctic
      notothenioid fish.
AB  - BACKGROUND: Confined within the freezing Southern Ocean, the Antarctic
      notothenioids have evolved to become both cold adapted and cold specialized. A
      marked signature of cold specialization is an apparent loss of the cellular heat
      shock response (HSR). As the HSR has been examined in very few notothenioid
      species to-date, it remains unknown whether HSR loss pervades the Antarctic
      radiation, or whether the broader cellular responses to heat stress has sustained
      similar loss. Understanding the evolutionary status of these responses in this
      stenothermal taxon is crucial for evaluating its adaptive potential to ocean
      warming under climate change. RESULTS: In this study, we used an acute heat
      stress protocol followed by RNA-Seq analyses to study the evolution of cellular
      wide transcriptional responses to heat stress across three select notothenioid
      lineages - the basal temperate and nearest non-Antarctic sister species Eleginops
      maclovinus serving as ancestral proxy, the cryopelagic Pagothenia borchgrevinki
      and the icefish Chionodraco rastrospinosus representing cold-adapted red-blooded
      and hemoglobinless Antarctic notothenioids respectively. E. maclovinus displayed
      robust cellular stress responses including the ER Unfolded Protein Response and
      the cytosolic HSR, cementing the HSR as a plesiomorphy that preceded Antarctic
      notothenioid radiation. While the transcriptional response to heat stress was
      minimal in P. borchgrevinki, C. rastrospinosus exhibited robust responses in the
      broader cellular networks especially in inflammatory responses despite lacking
      the classic HSR and UPR. CONCLUSION: The disparate patterns observed in these two
      archetypal Antarctic species indicate the evolutionary status in cellular ability
      to mitigate acute heat stress varies even among Antarctic lineages, which may
      affect their adaptive potential in coping with a warming world.

PMID- 30231869
TI  - Effects of a clinical pathway on antibiotic use in patients with community
      acquired pneumonia: a multi-site study in China.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a common condition with high
      mortality, morbidity and healthcare costs. This study aimed to determine whether
      clinical pathway (CP) implementation in different hospitals in China increased
      antibiotic compliance with the national CP in inpatients with CAP. METHODS: Chart
      reviews of CAP cases were conducted in 18 public hospitals from 3 different
      regions of China in 2015. Chi-square tests and the t-test were used to compare
      differences between hospitals that implemented CP (CP group) and those that did
      not (non-CP group). Multivariate logistic analysis was adopted to test whether CP
      implementation for CAP in hospitals affected their overall antibiotic use
      compliance rates with the national CP for CAP. RESULTS: The overall compliance
      rate with the national CP for inpatients with CAP was 43.69%. The compliance
      rates for timely initial antibiotic use, recommended antibiotic use and use of
      the recommended combination of antibiotics and the overall compliance rate were
      substantially higher in the CP group than in the non-CP group. A multivariate
      logistic model for overall compliance in inpatients with CAP showed that the
      hospitals in the CP group had greater overall compliance than those in the non-CP
      group (odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.16-2.71) after
      controlling for hospital and inpatient characteristics. CONCLUSION: In China, the
      overall compliance rate with the national CP for inpatients with CAP was low, but
      inpatients with CAP in the hospitals in the CP group received antibiotics more
      concordantly with the national CP. Since adherence to evidence-based care has
      been shown to improve clinical outcomes, internal and external support from
      hospitals is required to facilitate CP implementation for inpatients with CAP.
      Additionally, governmental commitment, hospital input and population involvement
      are required to improve antibiotic utilization.

PMID- 30231871
TI  - Correction to: A comparative genomic analysis of putative pathogenicity genes in
      the host-specific sibling species Colletotrichum graminicola and Colletotrichum
      sublineola.
AB  - Following the publication of this article [1], the authors informed us of the
      following error.

PMID- 30231870
TI  - Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial
      cells and wild-type mice.
AB  - BACKGROUND: The FDA-approved small-molecule drug ibrutinib is an effective
      targeted therapy for patients with chronic lymphocytic leukemia (CLL). Ibrutinib
      inhibits Bruton's tyrosine kinase (BTK), a kinase involved in B cell receptor
      signaling. However, the potential regulation of neuroinflammatory responses in
      the brain by ibrutinib has not been comprehensively examined. METHODS: BV2
      microglial cells were treated with ibrutinib (1 MUM) or vehicle (1% DMSO),
      followed by lipopolysaccharide (LPS; 1 MUg/ml) or PBS. RT-PCR,
      immunocytochemistry, and subcellular fractionation were performed to examine the
      effects of ibrutinib on neuroinflammatory responses. In addition, wild-type mice
      were sequentially injected with ibrutinib (10 mg/kg, i.p.) or vehicle (10% DMSO,
      i.p.), followed by LPS (10 mg/kg, i.p.) or PBS, and microglial and astrocyte
      activations were assessed using immunohistochemistry. RESULTS: Ibrutinib
      significantly reduced LPS-induced increases in proinflammatory cytokine levels in
      BV2 microglial and primary microglial cells but not in primary astrocytes.
      Ibrutinib regulated TLR4 signaling to alter LPS-induced proinflammatory cytokine
      levels. In addition, ibrutinib significantly decreased LPS-induced increases in p
      AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced
      neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways.
      Interestingly, ibrutinib also reduced LPS-induced BV2 microglial cell migration
      by inhibiting AKT signaling. Moreover, ibrutinib-injected wild-type mice
      exhibited significantly reduced microglial/astrocyte activation and COX-2 and IL
      1beta proinflammatory cytokine levels. CONCLUSIONS: Our data provide insights on
      the mechanisms of a potential therapeutic strategy for neuroinflammation-related
      diseases.

PMID- 30231872
TI  - Health care experiences of mothers of children with bronchiectasis in Counties
      Manukau, Auckland, New Zealand.
AB  - BACKGROUND: Bronchiectasis is a worsening public health problem in New Zealand.
      This study aimed to explore the health care experiences of mothers of children
      with bronchiectasis in the Counties Manukau District Health Board area of
      Auckland, New Zealand. METHODS: Semi-structured interviews were undertaken with
      ten mothers of children with bronchiectasis. Data were analysed using thematic
      analysis. RESULTS: Five themes emerged: 1) Searching for answers, describing
      mothers' search for a diagnosis; 2) (Dis)empowerment, describing mothers'
      acquisition of knowledge, leading to empowerment; 3) Health care and
      relationships, describing the impact of relationships on the mother's health care
      experiences; 4) A juggling act, describing the challenges of juggling health care
      with school, work and family; 5) Making it work, describing how mothers overcome
      barriers to access health care for their child. CONCLUSIONS: The health provider
      parent relationship was crucial for fostering positive health care experiences.
      Mothers' acquisition of knowledge facilitated empowerment within those
      relationships. Additionally, mothers' perceptions of the quality and benefit of
      health services motivated them to overcome barriers to accessing care. Study
      findings may help to improve health care experiences for parents of children with
      bronchiectasis if identified issues are addressed.

PMID- 30231873
TI  - Maternal socioeconomic factors and the risk of premature birth and low birth
      weight in Cyprus: a case-control study.
AB  - BACKGROUND: Prematurity and low birth weight are significant predictors of
      perinatal morbidity and mortality and are influenced by the overall health and
      socioeconomic status of the pregnant mother. Although Cyprus is characterized by
      the highest prematurity rate in Europe (13.1% in 2014), the relationship between
      maternal health and socioeconomic characteristics with prematurity and low birth
      weight has never been investigated. We aimed to investigate the association of
      maternal demographic, clinical and socioeconomic characteristics with premature
      delivery and low neonatal birth weight in Cyprus. METHODS: In a case-control
      design, questionnaire data were collected from 348 women who gave birth
      prematurely (cases) and 349 women who gave birth at term (controls). Information
      was obtained on gestation duration and birth weight as well as maternal
      demographic, socioeconomic and clinical profiles, including parameters such as
      smoking, body mass index, alcohol consumption, presence of gestational diabetes
      and mental health factors. RESULTS: Premature delivery was associated with
      greater maternal age (OR: 1.12, 95% CI: 1.06-1.18), absence of gestational
      diabetes (OR: 0.53, 95% CI: 0.30-0.97), long working hours (OR: 3.77, 95% CI:
      2.08-6.84) and emotional stress (OR: 8.5, 95% CI: 3.03-23.89). Within the cases
      group, emotional stress was also associated with lower birth-weight (beta: 
      323.68 (95% CI: -570.36, - 77.00). CONCLUSIONS: The findings of this study
      demonstrate the positive association of maternal psychological factors, working
      conditions as well as maternal age with prematurity and low birth weight in
      Cyprus. Additional, prospective, studies are needed in the country to further
      investigate these associations and inform public health intervention measures.

PMID- 30231874
TI  - Research on the horizontal equity of inpatient benefits among NCMS enrollees in
      China: evidence from Shaanxi Province.
AB  - BACKGROUND: Equity is an important goal for countries in formulating relevant
      health policies, and research on the equity of health services is more important
      for China, where the gap between the rich and poor is widening. The aims of this
      study are to explore to what extent the benefit equity of New Rural Cooperative
      Medical System enrollees has been achieved and to determine the geographical
      disparities in Shaanxi province and thus provide suggestions for future policy
      formulations. METHODS: Data were obtained from the fifth Health Service Survey of
      Shaanxi province in 2013. A two-step mode was used to analyse the influencing
      factors of the inpatient benefit rate and inpatient compensation fee.
      Concentration indexes and concentration curves were applied to measure the
      inequity of the inpatient benefit rate and inpatient compensation fee. The
      decomposition method was employed to explore the source of inequity and
      horizontal inequity. RESULTS: Based on a sample of 38,032 enrollees, our results
      showed that there were pro-rich inequities in the inpatient benefit rate and
      compensation fee. The concentration index of the inpatient benefit rate and
      compensation fee in 2013 were 0.064 and 0.174, respectively. The economic level
      (224.62%), self-evaluated health status (- 25.89%) and occupation status (-
      12.32%) were the primary three contributors to the inequity of the inpatient
      benefit rate, and the economic level (106.16%) and age (- 2.88%) were the first
      two contributors to the inequity of the compensation fee. There were regional
      differences in the sources of inequities. Moreover, pro-rich horizontal inequity
      remained after standardizing health care needs. CONCLUSIONS: Our results
      indicated that there were pro-rich inequities in the inpatient benefit rate and
      compensation fee in the New Rural Cooperative Medical System. The economic levels
      of enrollees accounted for most of the existing inequity, followed by self
      evaluated health scores and age. Efforts should be made to strengthen policies
      and programmes in the New Rural Cooperative Medical System to achieve basic
      health services equity, such as implementing hierarchical medical treatments and
      reducing extra inpatient benefits for the rich.

PMID- 30231875
TI  - Effect of isolated left bundle-branch block on biventricular volumes and ejection
      fraction: a cardiovascular magnetic resonance assessment.
AB  - BACKGROUND: Left bundle branch block (LBBB) is associated with abnormal left
      ventricular (LV) contraction, and is frequently associated with co-morbid
      cardiovascular disease, but the effect of an isolated (i.e. in the absence of
      cardiovascular dissease) LBBB on biventricular volumes and ejection fraction (EF)
      is not well characterized. The objective of this study was to compare LV and
      right ventricular (RV) volumes and EF in adults with an isolated LBBB to matched
      healthy controls and to population-derived normative values, using cardiovascular
      magnetic resonance (CMR) imaging. METHODS: We reviewed our clinical
      echocardiography database and the Framingham Heart Study Offspring cohort CMR
      database to identify adults with an isolated LBBB. Age-, sex-, hypertension
      status, and body-surface area (BSA)-matched controls were identified from the
      Offspring cohort. All study subjects were scanned using the same CMR hardware and
      imaging sequence. Isolated-LBBB cases were compared with matched controls using
      Wilcoxon paired signed-rank test, and to normative reference values via Z-score.
      RESULTS: Isolated-LBBB subjects (n = 18, 10F) ranged in age from 37 to 82 years.
      An isolated LBBB was associated with larger LV end-diastolic and end-systolic
      volumes (both p < 0.01) and lower LVEF (56+/- 7% vs. 68+/- 6%; p  <0.001) with
      similar myocardial contraction fraction. LVEF in isolated LBBB was nearly two
      standard deviations (Z = - 1.95) below mean sex and age-matched group values. LV
      stroke volume, cardiac output, and mass, and all RV parameters were similar (p =
      NS) between the groups. CONCLUSIONS: Adults with an isolated LBBB have greater LV
      volumes and markedly reduced LVEF, despite the absence of overt cardiovascular
      disease. These data may be useful toward the clinical interpretation of imaging
      studies performed on patients with an isolated LBBB.

PMID- 30231876
TI  - Comparative genomics of molybdenum utilization in prokaryotes and eukaryotes.
AB  - BACKGROUND: Molybdenum (Mo) is an essential micronutrient for almost all
      biological systems, which holds key positions in several enzymes involved in
      carbon, nitrogen and sulfur metabolism. In general, this transition metal needs
      to be coordinated to a unique pterin, thus forming a prosthetic group named
      molybdenum cofactor (Moco) at the catalytic sites of molybdoenzymes. The
      biochemical functions of many molybdoenzymes have been characterized; however,
      comprehensive analyses of the evolution of Mo metabolism and molybdoproteomes are
      quite limited. RESULTS: In this study, we analyzed almost 5900 sequenced
      organisms to examine the occurrence of the Mo utilization trait at the levels of
      Mo transport system, Moco biosynthetic pathway and molybdoproteins in all three
      domains of life. A global map of Moco biosynthesis and molybdoproteins has been
      generated, which shows the most detailed understanding of Mo utilization in
      prokaryotes and eukaryotes so far. Our results revealed that most prokaryotes and
      all higher eukaryotes utilize Mo whereas many unicellular eukaryotes such as
      parasites and most yeasts lost the ability to use this metal. By characterizing
      the molybdoproteomes of all organisms, we found many new molybdoprotein-rich
      species, especially in bacteria. A variety of new domain fusions were detected
      for different molybdoprotein families, suggesting the presence of novel proteins
      that are functionally linked to molybdoproteins or Moco biosynthesis. Moreover,
      horizontal gene transfer event involving both the Moco biosynthetic pathway and
      molybdoproteins was identified. Finally, analysis of the relationship between
      environmental factors and Mo utilization showed new evolutionary trends of the Mo
      utilization trait. CONCLUSIONS: Our data provide new insights into the
      evolutionary history of Mo utilization in nature.

PMID- 30231879
TI  - A super-resolution method-based pipeline for fundus fluorescein angiography
      imaging.
AB  - BACKGROUND: Fundus fluorescein angiography (FFA) imaging is a standard diagnostic
      tool for many retinal diseases such as age-related macular degeneration and
      diabetic retinopathy. High-resolution FFA images facilitate the detection of
      small lesions such as microaneurysms, and other landmark changes, in the early
      stages; this can help an ophthalmologist improve a patient's cure rate. However,
      only low-resolution images are available in most clinical cases. Super-resolution
      (SR), which is a method to improve the resolution of an image, has been
      successfully employed for natural and remote sensing images. To the best of our
      knowledge, no one has applied SR techniques to FFA imaging so far. METHODS: In
      this work, we propose a SR method-based pipeline for FFA imaging. The aim of this
      pipeline is to enhance the image quality of FFA by using SR techniques. Several
      SR frameworks including neighborhood embedding, sparsity-based, locally-linear
      regression and deep learning-based approaches are investigated. Based on a
      clinical FFA dataset collected from Second Affiliated Hospital to Xuzhou Medical
      University, each SR method is implemented and evaluated for the pipeline to
      improve the resolution of FFA images. RESULTS AND CONCLUSION: As shown in our
      results, most SR algorithms have a positive impact on the enhancement of FFA
      images. Super-resolution forests (SRF), a random forest-based SR method has
      displayed remarkable high effectiveness and outperformed other methods. Hence,
      SRF should be one potential way to benefit ophthalmologists by obtaining high
      resolution FFA images in a clinical setting.

PMID- 30231878
TI  - Analysis of porcine body size variation using re-sequencing data of miniature and
      large pigs.
AB  - BACKGROUND: Domestication has led to substantial phenotypic and genetic variation
      in domestic animals. In pigs, the size of so called minipigs differs by one order
      of magnitude compared to breeds of large body size. We used biallelic SNPs
      identified from re-sequencing data to compare various publicly available wild and
      domestic populations against two minipig breeds to gain better understanding of
      the genetic background of the extensive body size variation. We combined two
      complementary measures, expected heterozygosity and the composite likelihood
      ratio test implemented in "SweepFinder", to identify signatures of selection in
      Minipigs. We intersected these sweep regions with a measure of differentiation,
      namely FST, to remove regions of low variation across pigs. An extraordinary
      large sweep between 52 and 61 Mb on chromosome X was separately analyzed based on
      SNP-array data of F2 individuals from a cross of Goettingen Minipigs and large
      pigs. RESULTS: Selective sweep analysis identified putative sweep regions for
      growth and subsequent gene annotation provided a comprehensive set of putative
      candidate genes. A long swept haplotype on chromosome X, descending from the
      Goettingen Minipig founders was associated with a reduction of adult body length
      by 3% in F2 cross-breds. CONCLUSION: The resulting set of genes in putative sweep
      regions implies that the genetic background of body size variation in pigs is
      polygenic rather than mono- or oligogenic. Identified genes suggest alterations
      in metabolic functions and a possible insulin resistance to contribute to
      miniaturization. A size QTL located within the sweep on chromosome X, with an
      estimated effect of 3% on body length, is comparable to the largest known in pigs
      or other species. The androgen receptor AR, previously known to influence pig
      performance and carcass traits, is the most obvious potential candidate gene
      within this region.

PMID- 30231880
TI  - Hypolipidemic effect of Fragarianilgerrensis Schlecht. medicine compound on
      hyperlipidemic rats.
AB  - BACKGROUND: Fragarianilgerrensis Schlecht. medicine compound (FN-MC) is a kind of
      Chinese herbs' compound consisted of Fragarianilgerrensis Schlecht. and Centella
      asiatica (L.) Urban. The study was to investigate the hypolipidemia effect of FN
      MC in a hypolipidemic rat model. METHODS: Male SD rats were randomly divided into
      five groups: normal-fat diet (NFD) group, high-fat diet (HFD) group, FN-MC (2
      g/Kg) group, FN-MC (4 g/Kg) group and simvastatin (PDC) group. After FN-MC
      treatment, body weight, food intake, serum and hepatic biochemistry parameters of
      rats were measured and the pathological changes of liver and its cells were
      observed by optical microscope and transmission electron microscopy. RESULTS: The
      results showed that FN-MC significantly decreased the levels of serum
      triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C),
      apolipoprotein B (ApoB) and hepatic malondialdehyde (MDA), while increased serum
      high-density lipoprotein (HDL-C), apolipoprotein A1 (ApoA1) and hepatic
      Superoxide Dismutase (SOD). FN-MC also improved the structure of liver and
      decreased the lipid drops in the cytoplasm significantly. In addition, FN-MC
      significantly decreased the weight gain and had no significant effects on food
      intake. CONCLUSIONS: The study suggested that FN-MC exhibited strong ability to
      improve the dyslipidemia and prevent hepatic fatty deposition in rats fed with
      high-fat diet. Meanwhile, FN-MC exerted anti-obesity and antioxidant properties.
      HIGHLIGHTS: Fragarianilgerrensis Schlecht. medicine compound possesses a
      hypolipidemic effect on hyperlipidemic rat model Fragarianilgerrensis Schlecht.
      medicine compound administration improves the antioxidant capacity of rats
      Fragarianilgerrensis Schlecht. medicine compound prevents hepatic fatty
      deposition.

PMID- 30231881
TI  - IGFBP6 controls the expansion of chemoresistant glioblastoma through paracrine
      IGF2/IGF-1R signaling.
AB  - BACKGROUND: Glioblastomas (GBMs), the most common and most lethal of the primary
      brain tumors, are characterized by marked intra-tumor heterogeneity. Several
      studies have suggested that within these tumors a restricted population of
      chemoresistant glioma cells is responsible for recurrence. However, the gene
      expression patterns underlying chemoresistance are largely unknown. Numerous
      efforts have been made to block IGF-1R signaling pathway in GBM. However, those
      therapies have been repeatedly unsuccessful. This failure may not only be due to
      the complexity of IGF receptor signaling, but also due to complex cell-cell
      interactions in the tumor mass. We hypothesized that differential expression of
      proteins in the insulin-like growth factor (IGF) system underlie cell-specific
      differences in the resistance to temozolomide (TMZ) within GBM tumors. METHODS:
      Expression of IGF-1R was analyzed in cell lines, patient-derived xenograft cell
      lines and human biopsies by cell surface proteomics, flow cytometry,
      immunofluorescence and quantitative real time polymerase chain reaction (qRT
      PCR). Using gain-of-function and loss-of-function strategies, we dissected the
      molecular mechanism responsible for IGF-binding protein 6 (IGFBP6) tumor
      suppressor functions both in in vitro and in vivo. Site direct mutagenesis was
      used to study IGFBP6-IGF2 interactions. RESULTS: We determined that in human
      glioma tissue, glioma cell lines, and patient-derived xenograft cell lines,
      treatment with TMZ enhances the expression of IGF1 receptor (IGF-1R) and IGF2 and
      decreases the expression of IGFBP6, which sequesters IGF2. Using chemoresistant
      and chemosensitive wild-type and transgenic glioma cells, we further found that a
      paracrine mechanism driven by IGFBP6 secreted from TMZ-sensitive cells abrogates
      the proliferation of IGF-1R-expressing TMZ-resistant cells in vitro and in vivo.
      In mice bearing intracranial human glioma xenografts, overexpression of IGFBP6 in
      TMZ-resistant cells increased survival. Finally, elevated expression of IGF-1R
      and IGF2 in gliomas associated with poor patient survival and tumor expression
      levels of IGFBP6 directly correlated with overall survival time in patients with
      GBM. CONCLUSIONS: Our findings support the view that proliferation of
      chemoresistant tumor cells is controlled within the tumor mass by IGFBP6
      producing tumor cells; however, TMZ treatment eliminates this population and
      enriches the TMZ-resistant cell populationleading to accelerated growth of the
      entire tumor mass.

PMID- 30231877
TI  - Nano based drug delivery systems: recent developments and future prospects.
AB  - Nanomedicine and nano delivery systems are a relatively new but rapidly
      developing science where materials in the nanoscale range are employed to serve
      as means of diagnostic tools or to deliver therapeutic agents to specific
      targeted sites in a controlled manner. Nanotechnology offers multiple benefits in
      treating chronic human diseases by site-specific, and target-oriented delivery of
      precise medicines. Recently, there are a number of outstanding applications of
      the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic
      agents etc.) in the treatment of various diseases. The current review, presents
      an updated summary of recent advances in the field of nanomedicines and nano
      based drug delivery systems through comprehensive scrutiny of the discovery and
      application of nanomaterials in improving both the efficacy of novel and old
      drugs (e.g., natural products) and selective diagnosis through disease marker
      molecules. The opportunities and challenges of nanomedicines in drug delivery
      from synthetic/natural sources to their clinical applications are also discussed.
      In addition, we have included information regarding the trends and perspectives
      in nanomedicine area.

PMID- 30231882
TI  - Related factors of quality of life of type 2 diabetes patients: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Diabetes is a chronic disease, and it could affect both health and
      quality of life (QOL). A lot of studies have reported some predictors of QOL of
      type 2 diabetes patients. While their results were not completely consistent. So
      the aim of our study was finding out the related factors (including
      characteristics related to the disease, life styles and mental health factors) of
      QOL of type 2 diabetes patients. METHODS: We searched Cochrane library, EmBase,
      PubMed and CNKI databases for published studies that evaluated the related
      factors of QOL of type 2 diabetes patients by using a proper statistic method and
      had effect sizes (OR or beta) and 95% confidence intervals from January 1st 2000
      to May 31st 2016. Any study types were acceptable, and we excluded the reviews,
      letters, editorials and pooled analyses. The data were analyzed using STATA
      software (Version 12.0; Stata Corporation). Effect sizes and 95% confidence
      intervals were calculated to evaluate the relationship between these factors and
      QOL. RESULTS: Eighteen studies were included into our systematic review and meta
      analysis, totaling 57,109 type 2 diabetes patients. Do more physical exercises
      (The pooled ORs ranged from 0.635 to 0.825 for different scales, less than 1.00),
      glucose check more frequently [pooled OR (95%CI): 0.175 (0.041, 0.756)] were
      associated with a better QOL. Presence of complications (The pooled ORs ranged
      from 1.462 to 3.038 for different scales, more than 1.00), presence of
      hypertension [pooled OR (95%CI): 1.389 (1.173, 1644)], longer duration of
      diabetes [pooled OR (95%CI): 1.865 (1.088, 3.197)], diet with more red meat
      [pooled OR (95%CI): 2.085 (1.063, 4.089)] and depression (The pooled ORs ranged
      from 3.003 to 11.473 for different scales, higher than 1.00) were associated with
      a worse QOL. CONCLUSION: The results of this study show that physical exercise,
      glucose check frequently, complications, hypertension, duration of diabetes, diet
      with more red meat, and depression were associated with the QOL of type 2
      diabetes patients.

PMID- 30231884
TI  - Correction to: ONE SHOT - single shot radiotherapy for localized prostate cancer:
      study protocol of a single arm, multicenter phase I/II trial.
AB  - Following publication of the original article [1], the authors reported that one
      of the authors' names is spelled incorrectly. In this Correction the incorrect
      and correct author name are shown. The original publication of this article has
      been corrected.

PMID- 30231883
TI  - A longitudinal study of the prevalence and characteristics of breast disorders
      detected by clinical breast examination during pregnancy and six months
      postpartum in Ibadan, Southwestern Nigeria.
AB  - BACKGROUND: Breast disorders cause great anxiety for women especially when they
      occur in pregnancy because breast cancer is the most common cause of cancer
      related deaths in women. Majority of the disorders are Benign Breast Diseases
      (BBD) with various degrees of associated breast cancer risks. With increasing
      breast cancer awareness in Nigeria, we sought to determine the prevalence and
      characteristics of breast disorders among a cohort of pregnant women. METHODS: A
      longitudinal study of 1248 pregnant women recruited in their first trimester-
      till 26 weeks gestational age consecutively from selected antenatal clinics
      (ANCs), in Ibadan, Southwest Nigeria. A pretested interviewer- administered
      questionnaire was used to collect information at recruitment. Clinical Breast
      Examination (CBE) using MammaCare(r) technique was performed at recruitment and
      follow up visits at third trimester, six weeks postpartum and six months
      postpartum. Women with breast disorders were referred for Breast Ultrasound Scan
      (BUS) and those with Breast Imaging Reporting and Data System (BIRADS) >=4 had
      ultrasound guided biopsy. Statistical analysis was performed using Stata version
      14. RESULTS: Mean age of participants was 29.7 +/- 5.2 years and mean gestational
      age at recruitment was 20.4 +/- 4.4 weeks. Seventy-two participants (5.8%) had a
      past history of BBD and 345 (27.6%) were primigravidae. Overall, breast disorder
      was detected among 223 (17.9%) participants and 149 (11.9%) had it detected at
      baseline. Findings from the CBE showed that 208 (69.6%) of 299 breast disorders
      signs found were palpable lumps or thickenings in the breast, 28 (9.4%) were
      persistent pain, and 63 (21.1%) were abscesses, infection and mastitis. Twenty
      out of 127 (15.7%) participants who had BUS performed were classified as BIRADS
      >=3. Lesions found by BUS were reactive lymph nodes (42.5%), prominent ducts
      (27.1%), fibroadenoma (9.6%), breast cysts (3.8%) and fibrocystic changes (2.5%).
      No malignant pathology was found on ultrasound guided biopsy. CONCLUSIONS: Breast
      lump is a major breast disorder among pregnant women attending antenatal clinics
      in Ibadan. Routine clinical breast examination and follow up of pregnant women
      found with breast disorders could facilitate early detection of pregnancy
      associated breast cancer in low resource settings.

PMID- 30231885
TI  - Identifying factors associated with depression among men living with HIV/AIDS and
      undergoing antiretroviral therapy: a cross-sectional study in Heilongjiang,
      China.
AB  - BACKGROUND: Depression is common among people living with HIV/AIDS; however,
      studies focusing on the depression of men living with HIV/AIDS are limited.
      Therefore, we examined the prevalence of depression and its associated factors
      among men living with HIV/AIDS in China. METHODS: A cross-sectional questionnaire
      survey was conducted in Harbin, China between March and August in 2013. Two
      hundred twenty participants completed the Burns Depression Checklist, the Berger
      HIV Stigma, and the SPIEGEL questionnaire. We also investigated demographics,
      family support, hostility, and the antiretroviral therapy side effects of men
      living with HIV/AIDS. RESULTS: More than 40% of respondents had depressive
      symptoms and worry about the health was the major symptom of depression (40.9%).
      The logistic regression model indicated that bad sleep quality (OR = 3.452),
      hostility (OR = 1.120), perceived discrimination (OR = 1.110), and antiretroviral
      therapy side effects (OR = 1.083) were positively associated with depression.
      Family support (OR = 0.860) was negatively associated with depression for men
      living with HIV/AIDS. Demographic variables, HIV infection route, disease
      duration, and CD4+ cell count had no significant associations with depression.
      CONCLUSION: Although China's work of national HIV prevention and treatment has
      made much progress during the past several years, the prevalence of depression
      among men living with patients with HIV/AIDS is still prominent. The strongest
      factor associated with depression among men living with HIV/AIDS was sleep
      quality. Future studies should explore the effects of interventions for
      depression among PLWHA.

PMID- 30231887
TI  - How do gender and disability influence the ability of the poor to benefit from
      pro-poor health financing policies in Kenya? An intersectional analysis.
AB  - BACKGROUND: Health inequity has mainly been linked to differences in economic
      status, with the poor facing greater challenges accessing healthcare than the
      less poor. To extend financial coverage to the poor and vulnerable, Kenya has
      therefore implemented several pro-poor health policy reforms. However, other
      social determinants of health such as gender and disability also influence health
      status and access to care. This study employed an intersectional approach to
      explore how gender disability and poverty interact to influence how poor women in
      Kenya benefit from pro-poor financing policies that target them. METHODS: We
      applied a qualitative cross-sectional study approach in two purposively selected
      counties in Kenya. We collected data using in-depth interviews with women with
      disabilities living in poverty who were beneficiaries of the health insurance
      subsidy programme and those in the lowest wealth quintiles residing in the health
      and demographic surveillance system. We analyzed data using a thematic approach
      drawing from the study's conceptual framework. RESULTS: Women with disabilities
      living in poverty often opted to forgo seeking free healthcare services because
      of their roles as the primary household providers and caregivers. Due to limited
      mobility, they needed someone to accompany them to health facilities, leading to
      greater transport costs. The absence of someone to accompany them and
      unaffordability of the high transport costs, for example, made some women forgo
      seeking antenatal and skilled delivery services despite the existence of a free
      maternity programme. The layout and equipment at health facilities offering care
      under pro-poor health financing policies were disability-unfriendly. The latter
      in addition to negative healthcare worker attitudes towards women with
      disabilities discouraged them from seeking care. Negative stereotypes against
      women with disabilities in the society led to their exclusion from public
      participation forums thereby limiting their awareness about health services.
      CONCLUSIONS: Intersections of gender, poverty, and disability influenced the
      experiences of women with disabilities living in poverty with pro-poor health
      financing policies in Kenya. Addressing the healthcare access barriers they face
      could entail ensuring availability of disability-friendly health facilities and
      public transport systems, building cultural competence in health service
      delivery, and empowering them to engage in public participation.

PMID- 30231886
TI  - Society for Cardiovascular Magnetic Resonance (SCMR) expert consensus for CMR
      imaging endpoints in clinical research: part I - analytical validation and
      clinical qualification.
AB  - Cardiovascular disease remains a leading cause of morbidity and mortality
      globally. Changing natural history of the disease due to improved care of acute
      conditions and ageing population necessitates new strategies to tackle conditions
      which have more chronic and indolent course. These include an increased
      deployment of safe screening methods, life-long surveillance, and monitoring of
      both disease activity and tailored-treatment, by way of increasingly personalized
      medical care. Cardiovascular magnetic resonance (CMR) is a non-invasive, ionising
      radiation-free method, which can support a significant number of clinically
      relevant measurements and offers new opportunities to advance the state of art of
      diagnosis, prognosis and treatment. The objective of the SCMR Clinical Trial
      Taskforce was to summarizes the evidence to emphasize where currently CMR-guided
      clinical care can indeed translate into meaningful use and efficient deployment
      of resources results in meaningful and efficient use. The objective of the
      present initiative was to provide an appraisal of evidence on analytical
      validation, including the accuracy and precision, and clinical qualification of
      parameters in disease context, clarifying the strengths and weaknesses of the
      state of art, as well as the gaps in the current evidence This paper is
      complementary to the existing position papers on standardized acquisition and
      post-processing ensuring robustness and transferability for widespread use.
      Themed imaging-endpoint guidance on trial design to support drug-discovery or
      change in clinical practice (part II), will be presented in a follow-up paper in
      due course. As CMR continues to undergo rapid development, regular updates of the
      present recommendations are foreseen.

PMID- 30231888
TI  - Kinetics of mRNA delivery and protein translation in dendritic cells using lipid
      coated PLGA nanoparticles.
AB  - BACKGROUND: Messenger RNA (mRNA) has gained remarkable attention as an
      alternative to DNA-based therapies in biomedical research. A variety of
      biodegradable nanoparticles (NPs) has been developed including lipid-based and
      polymer-based systems for mRNA delivery. However, both systems still lack in
      achieving an efficient transfection rate and a detailed understanding of the mRNA
      transgene expression kinetics. Therefore, quantitative analysis of the time
      dependent translation behavior would provide a better understanding of mRNA's
      transient nature and further aid the enhancement of appropriate carriers with the
      perspective to generate future precision nanomedicines with quick response to
      treat various diseases. RESULTS: A lipid-polymer hybrid system complexed with
      mRNA was evaluated regarding its efficiency to transfect dendritic cells (DCs) by
      simultaneous live cell video imaging of both particle uptake and reporter gene
      expression. We prepared and optimized NPs consisting of poly (lactid-co-glycolid)
      (PLGA) coated with the cationic lipid 1, 2-di-O-octadecenyl-3-trimethylammonium
      propane abbreviated as LPNs. An earlier developed polymer-based delivery system
      (chitosan-PLGA NPs) served for comparison. Both NPs types were complexed with
      mRNA-mCherry at various ratios. While cellular uptake and toxicity of either NPs
      was comparable, LPNs showed a significantly higher transfection efficiency of ~
      80% while chitosan-PLGA NPs revealed only ~ 5%. Further kinetic analysis elicited
      a start of protein translation after 1 h, with a maximum after 4 h and drop of
      transgene expression after 48 h post-transfection, in agreement with the
      transient nature of mRNA. CONCLUSIONS: Charge-mediated complexation of mRNA to
      NPs enables efficient and fast cellular delivery and subsequent protein
      translation. While cellular uptake of both NP types was comparable, mRNA
      transgene expression was superior to polymer-based NPs when delivered by lipid
      polymer NPs.

PMID- 30231889
TI  - Expression of the neuroprotective protein aryl hydrocarbon receptor nuclear
      translocator 2 correlates with neuronal stress and disability in models of
      multiple sclerosis.
AB  - BACKGROUND: Axonal degeneration and neuronal loss have been described as the
      major causes of irreversible clinical disability in multiple sclerosis (MS). The
      aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) protein has been
      associated with neuroprotection in models of ischemia and neuronal responses to
      stressors. METHODS: To characterize its potential to influence inflammatory
      neurodegeneration, we examined ARNT2 expression in the experimental autoimmune
      encephalomyelitis (EAE) model of MS and characterized mediators that influence
      ARNT2 expression as well as plausible partners and targets. RESULTS: Arnt2
      message and protein levels dropped significantly in EAE spinal cords as disease
      developed and were lowest at peak disability. ARNT2 expression is prominent in
      neuronal cell bodies within the gray matter with some staining in glial
      fibrillary acidic protein (GFAP)+ astrocytes in healthy animals. At peak disease,
      ARNT2 expression is reduced by 20-50% in gray matter neurons compared to healthy
      controls. ARNT2 intensity in neurons throughout the EAE spinal cord correlated
      inversely with the degree of immune cell infiltration (r = - 0.5085, p < 0.01)
      and axonal damage identified with SMI32 staining (r = - 0.376, p = 0.032). To
      understand the relationship between ARNT2 expression and neuronal health, we
      exposed enriched cortical cultures of neurons to hydrogen peroxide (H2O2) to
      mimic oxidative stress. H2O2 at lower doses rapidly increased ARNT2 protein
      levels which returned to baseline within 3-4 h. Exposure to higher doses of H2O2)
      dropped ARNT2 levels below baseline, preceding cytotoxicity measured by
      morphological changes and lactate dehydrogenase release from cells. Decreases in
      ARNT2 secondary to staurosporine and H2O2 preceded increases in cleaved caspase 3
      and associated apoptosis. We also examined expression of neuronal pas 4 (Npas4),
      whose heterodimerization with ARNT2 drives expression of the neurotrophic factor
      brain-derived neurotrophic factor (Bdnf). Like ARNT2, Npas4 levels also decline
      at the onset of EAE and are linked to decreases in Bdnf. In vitro, H2O2 exposure
      drives Npas4 expression that is tied to increases in Bdnf. CONCLUSION: Our data
      support ARNT2 as a neuronal transcription factor whose sustained expression is
      linked to neuronal and axonal health, protection that may primarily be driven
      through its partnering with Npas4 to influence BDNF expression.

PMID- 30231892
TI  - Sexual and physical abuse and its determinants among street children in Addis
      Ababa, Ethiopia 2016.
AB  - BACKGROUND: The life and health of street children is becoming a global concern.
      Street children are vulnerable to a variety of problems including physical,
      psychological and sexual exploitations as well as social isolation. Therefore, it
      was the purpose of this study to point out the experience of sexual and physical
      exploitation and its determinant factors among street children in Addis Ababa,
      the capital city of Ethiopia. METHODOLOGY: A phenomenological qualitative method
      was conducted from March to June 2016 in Addis Ababa, Ethiopia. Data were
      collected from street children by focus group discussion (FGD) and in-depth
      interview. Open code was used to analyze data. The transcribed note was
      translated. Following this coding was done. Based on a coding book, major themes
      and main categories were developed and analyzed. RESULT: The study has explored
      the life experience of street children in the city. Deaths of parents/unhealthy
      relationship of extended families forced them be on a street. Thus, flee to
      street to search for work was the main reason for joining to a street. Street
      children are vulnerable to sexual and physical exploitations on a daily basis.
      For street children, street is the world characterized by misery deprivation,
      physical, verbal and sexual abuse and become daily victims of violence. There is
      no safe place for the children of on-street. Most street children are involved in
      all types of sex; heterosexual, bisexual, homosexual and group sex are common
      among themselves and out siders. They are involved highly in transactional sex
      for survival. Drug use, stress and depression are common experiences. Thus, they
      were socially isolated. The main challenges of living on a street are lack of
      basic needs, social isolation, lack of safety and security and being out of
      school are the common problems these vulnerable groups are facing. CONCLUSIONS:
      Street children are at high risk of sexual and physical exploitation.
      Interventions targeting integration and reunion with families, reduction of
      physical and sexual exploitation, access to education, mental health promotion
      and reduction of drug use behavior should be taken in to considerations.

PMID- 30231890
TI  - Assessment of denosumab treatment effects and imaging response in patients with
      giant cell tumor of bone.
AB  - BACKGROUND: Denosumab has been shown to reduce tumor size and progression, reform
      mineralized bone, and increase intralesional bone density in patients with giant
      cell tumor of bone (GCTB); however, radiologic assessment of tumors in bone is
      challenging. The study objective was to assess tumor response to denosumab using
      three different imaging parameters in a prespecified analysis in patients with
      GCTB from two phase 2 studies. METHODS: The studies enrolled adults and
      adolescents (skeletally mature and at least 12 years of age) with
      radiographically measurable GCTB that were given denosumab 120 mg every 4 weeks,
      with additional doses on days 8 and 15 of cycle 1. The proportion of patients
      with an objective tumor response was assessed using either Response Evaluation
      Criteria in Solid Tumors version 1.1 (RECIST), European Organisation for Research
      and Treatment of Cancer response criteria (positron emission tomography [PET]
      scan criteria), or inverse Choi density/size (ICDS) criteria. Target lesions were
      measured by computed tomography or magnetic resonance imaging (both studies), PET
      (study 2 only), or plain film radiograph (study 2 only). RESULTS: Most patients
      (71.6%) had an objective tumor response by at least one response criteria. Per
      RECIST, 25.1% of patients had a response; per PET scan criteria, 96.2% had a
      response; per ICDS, 76.1% had a response. 68.5% had an objective tumor response
      >= 24 weeks. Using any criteria, crude incidence of response ranged from 56%
      (vertebrae/skull) to 91% (lung/soft tissue), and 98.2% had tumor control >= 24
      weeks. Reduced PET avidity appeared to be an early sign of response to denosumab
      treatment. CONCLUSION: Modified PET scan criteria and ICDS criteria indicate that
      most patients show responses and higher benefit rates than modified RECIST, and
      therefore may be useful for early assessment of response to denosumab. TRIAL
      REGISTRATION: ClinicalTrials.gov Clinical Trials Registry NCT00396279
      (retrospectively registered November 6, 2006) and NCT00680992 (retrospectively
      registered May 20, 2008).

PMID- 30231891
TI  - Characteristics of patients with thromboembolic disorders on warfarin therapy in
      resource limited settings.
AB  - BACKGROUND: Warfarin is a drug with narrow therapeutic index used in the
      management of thromboembolic disorders. Several factors affect its plasma
      concentrations with a resultant risk of toxicity. We examined the database of
      patients on warfarin therapy in order to establish the factors that affect the
      stability of INR and correlated them to clinical outcomes in resource limited
      settings. METHODS: We analysed retrospective data of patients admitted to adult
      medical wards at Moi Teaching and Referral Hospital (MTRH) in 2015. Inclusion
      criteria were patients with thromboembolic and related disorders and on warfarin
      treatment. Derived data included demographics, indications for warfarin use, co
      prescribed drugs, co-morbidities, INR measurements, duration of hospital stay and
      clinical outcomes. Descriptive statistics were used to summarize the data.
      Pearson's correlation coefficient was used to assess relationships between
      duration of hospitalization and number of INR tests. Regression splines were used
      to capture INR trends during the follow up period. Data was analysed using R v.
      3.3.1. RESULTS: A total of 310 patients had thromboembolic disorders, out of
      which 63 met the study criteria. The median age was 48 years, while the mean
      number of INR measurements was once every four days. Majority of patients did not
      achieve stable INR values, with only two having consecutive INR values within
      therapeutic goal. Patients who died had high INR levels. The median duration of
      hospital stay was 9 days (IQR: 7.0, 16.5). There was a significant correlation
      between length of stay in hospital and the number of times that INR were measured
      (Corr = 0.667, p < 0.001). The two most common indications for warfarin were DVT
      (64.4%) and atrial fibrillation (24.7%). All the patients had one or more
      comorbid conditions except for 11 with DVT alone, with cardiovascular diseases
      and infections being the most frequent, and on concomitant medications, majority
      of which are known to interact with warfarin. CONCLUSIONS: It was difficult to
      achieve stable INR under the prevailing conditions despite the frequent tests.
      The potential factors that may have contributed to the fluctuations include drug
      drug interactions, frequency of INR tests, comorbidities and the short duration
      of hospital stay.

PMID- 30231893
TI  - Requirements for the implementation of open door policies in acute psychiatry
      from a mental health professionals' and patients' view: a qualitative interview
      study.
AB  - BACKGROUND: Treating legally committed patients on open, instead of locked wards
      is controversially discussed and the affected stakeholders (patients, mental
      health professionals) have ambiguous views on the benefits and disadvantages. The
      study aims to assess the opinions and values of relevant stakeholders with regard
      to the requirements for implementing open wards in psychiatric hospitals.
      METHODS: Semi-structured interviews were conducted with 15 psychiatrists, 15
      psychiatric nurses and 15 patients, and were analyzed using qualitative content
      analysis. RESULTS: The interviewees identified conceptual, personnel and spatial
      requirements necessary for an open door policy. Observation and door watch
      concepts are judged to be essential for open wards, and patients appreciate the
      therapeutic value they hold. However, nurses find the door watch problematic. All
      groups suggest seclusion or small locked divisions as a possible way of handling
      agitated patients. All stakeholders agree that such concepts can only succeed if
      sufficient, qualified staff is available. They also agree that freedom of
      movement is a key element in the management of acutely ill patients, which can be
      achieved with an open door policy. Finally, the interviewees suggested removing
      the door from direct view to prevent absconding. CONCLUSIONS: For psychiatric
      institutions seeking to implement (partially) open wards, the present results may
      have high practical relevance. The stakeholders' suggestions also illustrate that
      fundamental clinical changes depend on resource investments which - at least at a
      certain point - might not be feasible for individual psychiatric institutions but
      presumably require initiatives on the level of mental health care providers or
      policy makers.

PMID- 30231894
TI  - The use of low-cost Android tablets to train community health workers in Mukono,
      Uganda, in the recognition, treatment and prevention of pneumonia in children
      under five: a pilot randomised controlled trial.
AB  - BACKGROUND: Since 2012, The World Health Organization and UNICEF have advocated
      for community health workers (CHWs) to be trained in Integrated Community Case
      Management (iCCM) of common childhood illnesses, such as pneumonia. Despite the
      effectiveness of iCCM, CHWs face many barriers to accessing training. This pilot
      study compares traditional training with using locally made videos loaded onto
      low-cost Android tablets to train CHWs on the pneumonia component of iCCM.
      METHODS: We conducted a pilot randomised controlled trial with CHWs in the Mukono
      District of Uganda. The unit of randomisation was the sub-county level, and the
      unit of analysis was at the level of the individual CHW. Eligible CHWs had
      completed basic iCCM training but had not received any refresher training on the
      pneumonia component of iCCM in the preceding 2 years. CHWs in the control group
      received training in the recognition, treatment, and prevention of pneumonia as
      it is currently delivered, through a 1-day, in-person workshop. CHWs allocated to
      the intervention group received training via locally made educational videos
      hosted on low-cost Android tablets. The primary outcome was change in knowledge
      acquisition, assessed through a multiple choice questionnaire before and after
      training, and a post-training clinical assessment. The secondary outcome was a
      qualitative evaluation of CHW experiences of using the tablet platform. RESULTS:
      In the study, 129 CHWs were enrolled, 66 and 63 in the control and intervention
      groups respectively. CHWs in both groups demonstrated an improvement in multiple
      choice question test scores before and after training; however, there was no
      statistically significant difference in the improvement between groups (t = 1.15,
      p = 0.254). There was a statistically significant positive correlation (Pearson's
      r = 0.26, p = 0.03) linking years of education to improvement in test scores in
      the control group, which was not present in the intervention group. The majority
      of CHWs expressed satisfaction with the use of tablets as a training tool;
      however, some reported technical issues (n = 9). CONCLUSION: Tablet-based
      training is comparable to traditional training in terms of knowledge acquisition.
      It also proved to be feasible and a satisfactory means of delivering training to
      CHWs. Further research is required to understand the impacts of scaling such an
      intervention. TRIAL REGISTRATION: Registered on 23/11/2016 at clinicaltrials.gov
      ( NCT02971449 ).

PMID- 30231895
TI  - Polymorphisms in the human serotonin receptor 1B (HTR1B) gene are associated with
      schizophrenia: a case control study.
AB  - BACKGROUND: Schizophrenia is associated with multiple neurotransmitter disorders,
      including serotonin (5-hydroxytryptamine, 5-HT). The neuromodulatory action of
      serotonin on brain function largely depends on the action of specific subtypes of
      serotonin receptors. The serotonin receptor 1B (HTR1B) gene has been proposed to
      play putative roles in the development of multiple emotional and psychiatric
      disorders. METHODS: To study the relationship of HTR1B polymorphisms and
      schizophrenia, gene information was drawn from a cohort of 310 schizophrenic
      patients (152 men and 158 women) and 313 healthy controls (153 men and 160 women)
      of northern Han Chinese descent. The chi2 test was used to compare allele and
      genotype distributions between case and control groups. The haplotype and linkage
      equilibrium were also assessed in two group comparisons. RESULTS: We detected 14
      SNPs. Male patients were observed to have higher frequencies of the A-allele and
      AA+AG genotype at rs1778258 than female patients (p = 0.012 and p = 0.015,
      respectively). Both the A-allele and AA+AG genotype were associated with
      schizophrenia risk (OR = 1.986 and OR = 2.061, respectively), although the
      statistical significance of the genotype was lost after Bonferroni correction.
      Linkage analysis showed that rs17273700, rs11568817, rs9361234 and rs58138557
      polymorphisms exhibit strong linkage disequilibrium (LD). In addition,
      schizophrenic patients show stronger linkage between 11,568,817 and rs130058 than
      healthy controls. CONCLUSIONS: HTR1B polymorphisms are associated with
      schizophrenia in the northern Han Chinese population, which provides an
      etiological reference for schizophrenia.

PMID- 30231897
TI  - Surgically assisted rapid maxillary expansion in lingual orthodontics -
      optimizing of coupling and timing : Best oral presentation from the 21st Meeting
      of German Society of Lingual Orthodontics.
AB  - BACKGROUND: Surgically assisted rapid maxillary expansion (SARME) is primarily
      used in adult orthodontics. In many cases it is followed by further surgery to
      address further anteroposterior and/or vertical discrepancies. Treatment times in
      such cases are often long with adult patients usually requesting invisible
      appliances. Lingual appliances can provide the mechanical control required as
      well as fulfil the aesthetic demands in such cases. However lingual appliances
      are usually custom made and indirectly bonded. Due to tooth movement following
      surgery there is usually a long delay before impressions can be made for
      customized lingual appliances. This results in a long delay before alignement and
      leveling can be commenced post-surgery. CASE PRESENTATIONS: Three cases are
      presented here demonstrating the simultaneous placement of bone anchored
      expansion devices for surgically assisted rapid maxillary expansion with
      customized lingual appliances. CONCLUSIONS: The combination of the two procedures
      allows the alignement and leveling to commence very soon after surgery
      significantly reducing treatment times. The design of the appliances and the
      clinical procedures are described and discussed.

PMID- 30231896
TI  - Amyloid positron emission tomography and cerebrospinal fluid results from a
      crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled,
      randomized phase II study in mild-to-moderate Alzheimer's disease (BLAZE).
AB  - BACKGROUND: We investigated the effect of crenezumab, a humanized anti-amyloid
      beta (Abeta) immunoglobulin (Ig)G4 monoclonal antibody, on biomarkers of amyloid
      pathology, neurodegeneration, and disease progression in patients with mild-to
      moderate Alzheimer's disease (AD). METHODS: This double-blind, placebo
      controlled, randomized phase II study enrolled patients with mild-to-moderate AD
      and a Mini-Mental State Examination (MMSE) score of 18-26. In part 1 of the
      study, patients were 2:1 randomized to receive low-dose subcutaneous (SC) 300 mg
      crenezumab every 2 weeks (q2w) or placebo for 68 weeks; in part 2, patients were
      2:1 randomized to receive high-dose intravenous (IV) 15 mg/kg crenezumab every 4
      weeks (q4w) or placebo for 68 weeks. The primary endpoint was change in amyloid
      burden from baseline to week 69 assessed by florbetapir positron emission
      tomography (PET) in the modified intent-to-treat population. Secondary endpoints
      were change from baseline to week 69 in cerebrospinal fluid (CSF) biomarkers and
      fluorodeoxyglucose PET, and change from baseline to week 73 in 12-point
      Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog12) and Clinical
      Dementia Rating Sum of Boxes (CDR-SB). Safety was assessed in patients who
      received at least one dose of study treatment. RESULTS: From August 2011 to
      September 2012, 91 patients were enrolled and randomized (low-dose SC cohort:
      crenezumab (n = 26) or placebo (n = 13); high-dose IV cohort: crenezumab (n = 36)
      or placebo (n = 16)). The primary endpoint was not met using a prespecified
      cerebellar reference region to calculate standard uptake value ratios (SUVRs)
      from florbetapir PET. Exploratory analyses using subcortical white matter
      reference regions showed nonsignificant trends toward slower accumulation of
      plaque amyloid in the high-dose IV cohort. In both cohorts, a significant mean
      increase from baseline in CSF Abeta(1-42) levels versus placebo was observed.
      Nonsignificant trends toward ADAS-Cog12 and CDR-SB benefits were identified in a
      mild (MMSE 20-26) subset of the high-dose IV cohort. No amyloid-related imaging
      abnormalities due to edema/effusion were observed. CONCLUSION: The primary
      endpoint was not met. Exploratory findings suggest potential Abeta target
      engagement with crenezumab and possible slower accumulation of plaque amyloid.
      Studies investigating the effects of higher doses of crenezumab on amyloid load
      and disease progression are ongoing. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01397578 . Registered on 18 July 2011.

PMID- 30231898
TI  - Leptin receptor gene polymorphisms and sex modify the association between
      acetaminophen use and asthma among young adults: results from two observational
      studies.
AB  - BACKGROUND: Epidemiologic studies have demonstrated associations between
      acetaminophen use and asthma. This investigation sought to determine whether sex
      modifies the acetaminophen-asthma association and whether leptin (LEP) and leptin
      receptor (LEPR) gene polymorphisms modulate the sex-specific associations.
      METHODS: Data from the Isle of Wight birth cohort (IOW; n = 1456, aged 18 years)
      and Kuwait University Allergy (KUA; n = 1154, aged 18-26 years) studies were
      analyzed. Acetaminophen use and current asthma were self-reported. Genotype
      information for eighteen polymorphisms in LEP and LEPR genes were available in
      the IOW study. Associations between acetaminophen use and asthma were stratified
      by sex and genotype. Poisson regression models with robust variance estimation
      were evaluated to estimate adjusted prevalence ratios (aPR) and 95% confidence
      intervals (CI). RESULTS: Acetaminophen use was dose-dependently associated with
      an increased prevalence of current asthma in the IOW and KUA studies. In both
      studies, sex-stratified analysis showed that acetaminophen use was associated
      with asthma among males, but not in females (Pinteraction <  0.05). Moreover, a
      sex- and genotype-stratified analysis of the IOW data indicated that
      acetaminophen was associated with asthma to a similar extent among males and
      females carrying two common alleles of LEPR polymorphisms. In contrast, among
      those carrying at least one copy of the minor allele of LEPR polymorphisms, the
      magnitude of association between acetaminophen use and asthma was pronounced
      among males (aPR = 6.83, 95% CI: 2.87-16.24), but not among females (aPR = 1.22,
      95% CI: 0.61-2.45). CONCLUSIONS: The identified sex-related effect modification
      of the acetaminophen-asthma association varied across LEPR genotypes, indicating
      that the sex-specific association was confined to individuals with certain
      genetic susceptibility. If the acetaminophen-asthma association is causal, then
      our findings will aid susceptibility-based stratification of at-risk individuals
      and augment preventive public health efforts.

PMID- 30231899
TI  - A protocol update for the Selenium Treatment and Chagasic Cardiomyopathy (STCC)
      trial.
AB  - : Several studies evaluating clinical forms of chronic Chagas disease show that
      about one-third of patients present cardiac involvement. Heart failure, sudden
      death and cardioembolic stroke are the main mechanisms of death in Chagas heart
      disease. The impact of specific etiologic treatment on the prognosis of patients
      with chronic Chagas heart disease is very limited regardless of the presence or
      absence of heart failure. Patients with symptomatic Chagas heart disease present
      serum selenium (Se) levels lower than patients without Chagas heart disease.
      Moreover, Se supplementation in animal models showed promising results. The aim
      of this trial is to estimate the effect of Se treatment on prevention of heart
      disease progression in patients with Chagas cardiomyopathy. However, we had to
      introduce some protocol modifications in order to keep trial feasibility, as
      follows: the primary outcome was restricted to left ventricular ejection fraction
      as a continuous variable, excluding disease progression; the follow-up period was
      decreased from 5 years to 1 year, an adjustment that might increase the
      participation rate of our study; the superior age limit was increased from 65 to
      75 years; and diabetes mellitus was no longer considered an exclusion criterion.
      All of these protocol modifications were extensively debated by the research team
      enrolled in the design, recruitment and conduction of the clinical trial to
      guarantee a high scientific quality. TRIAL REGISTRATION: Clinical Trials.gov,
      NCT00875173 . Registered on 20 October 2008.

PMID- 30231901
TI  - Serological and entomological survey of canine leishmaniasis in Lampedusa island,
      Italy.
AB  - BACKGROUND: During last decade Lampedusa island (Italy) has been interested by a
      deep social change caused by the massive arrival of migrants from north Africa.
      The goal of this study was to evaluate current CanL burden and risk factors for
      Visceral Leishmaniosis (VL) on Lampedusa, actually based on very few data
      obtained in a previous study performed fifteen years ago. Two hundred and forty
      two dogs were enrolled for the detection of Leishmania infantum infection by
      serology. In addition, an entomological investigation was performed to confirm
      the presence of Leishmania-vectors. RESULTS: Seroprevalence was of 54.13%. 223
      sand flies specimens were collected. Among them, 4 species were identified:
      Phlebotomus perniciosus, P. papatasi, P. neglectus, Sergentomia minuta, with P.
      perniciosus the most abundant (67.7%; p < 0.01). CONCLUSION: The high proportion
      of seropositive dogs together with the presence of the most competent vector for
      L. infantum, P. perniciosus, demonstrate that L. infantum abundantly circulates
      in the island and may constitute a risk for people, particularly for hosted
      migrants.

PMID- 30231902
TI  - An unusual case of extensive truncal cutaneous larva migrans in a Cameroonian
      baby: a case report.
AB  - BACKGROUND: Cutaneous larva migrans is a neglected zoonotic helminthic disease
      which is paradoxically underreported in low-income and middle-income countries
      from where a majority of the cases emanate. It presents as migratory, raised,
      erythematous serpentine lesions, responsive to treatment with antihelminthics. It
      is common in children, but rare in babies. We report an unusual case of cutaneous
      larva migrans in a Cameroonian baby. CASE PRESENTATION: We report the case of a 9
      month-old Cameroonian baby girl, whose mother had the habit of drying the child's
      clothes on the grass in her courtyard. The child was brought to our hospital
      after she developed itchy, snake-like, slowly progressing lesions on her abdomen
      and chest. An examination revealed multiple raised serpentine and erythematous
      skin lesions consistent with cutaneous larva migrans which subsided on
      antihelminthic and antihistaminic therapy. CONCLUSIONS: Cutaneous larva migrans
      is an endemic disease with predilection for poor and vulnerable persons.
      Preventive efforts such as wearing of slippers, usage of drying lines, and
      deworming of pets are crucial in preventing the occurrence of this disease and
      should be encouraged.

PMID- 30231900
TI  - Comparative genome analysis of jujube witches'-broom Phytoplasma, an obligate
      pathogen that causes jujube witches'-broom disease.
AB  - BACKGROUND: JWB phytoplasma is a kind of insect-transmitted and uncultivable
      bacterial plant pathogen causeing a destructive Jujube disease. To date, no
      genome information about JWB phytoplasma has been published, which hindered its
      characterization at genomic level. To understand its pathogenicity and ecology,
      the genome of a JWB phytoplasma isolate jwb-nky was sequenced and compared with
      other phytoplasmas enabled us to explore the mechanisms of genomic rearrangement.
      RESULTS: The complete genome sequence of JWB phytoplasma (jwb-nky) was
      determined, which consisting of one circular chromosome of 750,803 bp with a GC
      content of 23.3%. 694 protein-encoding genes, 2 operons for rRNA genes and 31
      tRNA genes as well as 4 potential mobile units (PMUs) containing clusters of DNA
      repeats were identified. Based on PHIbaes analysis, a large number of genes were
      genome-specific and approximately 13% of JWB phytoplasma genes were predicted to
      be associated with virulence. Although transporters for maltose,
      dipeptides/oligopeptides, spermidine/putrescine, cobalt, Mn/Zn and methionine
      were identified, KEGG pathway analysis revealed the reduced metabolic
      capabilities of JWB phytoplasma. Comparative genome analyses between JWB
      phytoplasma and other phytoplasmas shows the occurrence of large-scale gene
      rearrangements. The low synteny with other phytoplasmas indicated that the
      expansion of multiple gene families/duplication probably occurred separately
      after differentiation. CONCLUSIONS: In this study, the complete genome sequence
      of a JWB phytoplasma isolate jwb-nky that causing JWB disease was reported for
      the first time and a number of species-specific genes were identified in the
      genome. The study enhanced our understandings about genomic basis and the
      pathogenicity mechanism of this pathogen, which will aid in the development of
      improved strategies for efficient management of JWB diseases.

PMID- 30231903
TI  - Exploring physicians' decision-making in hospital readmission processes - a
      comparative case study.
AB  - BACKGROUND: Hospital readmissions is an increasingly serious international
      problem, associated with higher risks of adverse events, especially in elderly
      patients. There can be many causes and influential factors leading to hospital
      readmissions, but they are often closely related, making hospital readmissions an
      overall complex area. In addition, a comprehensive coordination reform was
      introduced into the Norwegian healthcare system in 2012. The reform changed the
      premises for readmissions with economic incentives enhancing early transfer from
      secondary to primary care, making research on readmissions in the municipalities
      more urgent than ever. General practitioners (GPs) and nursing home physicians,
      have traditionally held a gatekeepers function in hospital readmissions from the
      municipal healthcare service, as they are the main decision-makers in questions
      of hospital readmissions. Still, the GPs' gatekeeper function is an under
      investigated area in hospital readmission research. The aim of the study was to
      increase knowledge about factors that lead to hospital readmissions among elderly
      in municipal healthcare, with special attention to GPs' and nursing home
      physicians' decision making. METHOD: The study was conducted as a comparative
      case study. Two municipalities affiliated with the same hospital, but with
      different readmission rates were recruited. Twenty GPs and nursing home
      physicians from each municipality were recruited and interviewed. Forty hours of
      observation were conducted during the huddles in one long-term and one short-term
      nursing home in each municipality. RESULTS: Seven themes describing how different
      factors influence physicians' decision-making in the hospital readmission process
      in two municipalities were identified. Poor communication, continuity and
      information flow account for hospital readmissions in both municipalities.
      Several factors, including nurse staffing and competence, patients and their
      families, time constraints and experience affected physicians' decision-making.
      CONCLUSION: Communication, continuity and information flow contributed to
      hospital readmissions in both municipalities. The cross-case analysis revealed
      slight differences between municipalities. More research focusing on GPs' and
      nursing home physicians' decision-making, nursing home nurses and home care
      nurses' experience of hospital readmissions and discharges is needed.

PMID- 30231904
TI  - From motor performance to participation: a quantitative descriptive study in
      adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay.
AB  - BACKGROUND: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is
      a recessive neurological disorder with cerebellar, pyramidal and neuropathic
      features. Natural history data are urgently needed to increase trial readiness.
      This study aimed to describe the clinical phenotype including dexterity,
      coordination, strength, mobility, balance, disease severity, participation, and
      quality of life observed in adults with ARSACS homozygous for the c.8844delT
      mutation. METHODS: Cross-sectional study with comparisons between disease stages
      and with reference values. Outcome measures included Standardized Finger-to-Nose
      Test, Grip/pinch strength, LEMOCOT, Six-Minute Walk Test, 10-Meter Walk Test,
      Berg Balance Scale, Spastic Paraplegia Rating Scale, Scale for the Assessment and
      Rating of Ataxia, LIFE-H, and SF-12. RESULTS: Twenty-eight participants were
      recruited with a mean age of 38.1 years. The majority presented with lower limb
      coordination and fine dexterity scores below three standard deviations compare to
      reference values, scored under predicted values for mobility measures and were at
      increased risk of fall. Participants at an earlier disease stage performed better
      than the others, but individual variability was observed. CONCLUSIONS: Results
      showed overall impaired motor performances and, even in a genetically homogeneous
      ARSACS population, an individual variability within disease stages. This study
      lays the foundation for a longitudinal study using quantified measurements.

PMID- 30231906
TI  - Cross-sectional study on risk factors for Porcine Reproductive and Respiratory
      Syndrome virus sow herd instability in German breeding herds.
AB  - BACKGROUND: Porcine Reproductive and Respiratory Syndrome virus (PRRSV)
      stability, besides meeting production targets, is also a requirement for several
      control options of PRRS in pig breeding farms. This study aimed to investigate
      the frequency of, and risk factors associated with, PRRSV instability in pig
      breeding farms in northern Germany. In 120 sow herds, a questionnaire on
      production and management parameters was filled, and blood samples from 30
      suckling pigs from 10 different litters were taken and examined using real-time
      polymerase chain reaction (PCR). RESULTS: PRRSV was detected in 32 herds (27%),
      thus classified as PRRSV-unstable. According to multivariable logistic regression
      analysis, a suckling period <= 21 days, a low distance between the cadaver
      collection site and the actual sow barn, >= 2 pig herds in a 1000 m radius,
      presence of external employees, a time interval between purchase of gilts of <= 9
      weeks and a 1- or 2-weekly farrowing rhythm were associated with a higher risk of
      PRRSV instability. CONCLUSIONS: External and internal biosecurity as well as
      management factors were associated with PRRSV instability, which could be
      targeted by farmers and veterinarians to help them to achieve PRRSV PCR-negative
      status and in the control of PRRS.

PMID- 30231907
TI  - When to initiate ECMO with low likelihood of success.

PMID- 30231905
TI  - Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high
      plasma levels as combined risk markers for sepsis survival.
AB  - BACKGROUND: Nitric oxide (NO) regulates processes involved in sepsis progression,
      including vascular and immune function. NO is generated by nitric oxide synthases
      (NOS) from L-arginine. Cellular L-arginine uptake is inhibited by symmetric
      dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) is a competitive
      inhibitor of NOS. Increased inhibitor blood concentrations lead to reduce NO
      bioavailability. The aim of this study was to determine whether plasma
      concentrations of SDMA and ADMA are markers for sepsis survival. METHOD: This
      prospective, single center study involved 120 ICU patients with sepsis. Plasma
      SDMA and ADMA were measured on admission (day 1), day 3 and day 7 by mass
      spectrometry together with other laboratory markers. The sequential organ failure
      assessment (SOFA) score was used to evaluate sepsis severity. Survival was
      documented until day 28. Groups were compared using the Mann-Whitney U test, chi
      squared test or non-parametric analysis of variance (ANOVA). Mortality was
      assessed using Kaplan-Meier curves and compared using the log-rank test. Specific
      risk groups were identified using a decision tree algorithm. RESULTS: Median
      plasma SDMA and ADMA levels were significantly higher in non-survivors than in
      survivors of sepsis: SDMA 1.14 vs. 0.82 MUmol/L (P = 0.002) and ADMA 0.93 vs.
      0.73 MUmol/L (P = 0.016). ANOVA showed that increased plasma SDMA and ADMA
      concentrations were significantly associated with SOFA scores. The 28-day
      mortality was compared by chi-square test: for SDMA the mortality was 12% in the
      lower, 25% in the intermediate and 43% in the 75th percentile (P = 0.018); for
      ADMA the mortality was 18-20% in the lower and intermediate but 48% in the 75th
      percentile (P = 0.006). The highest mortality (61%) was found in patients with
      plasma SDMA > 1.34 together with ADMA levels > 0.97 MUmol/L. CONCLUSIONS:
      Increased plasma concentrations of SDMA and ADMA are associated with sepsis
      severity. Therefore, our findings suggest reduced NO bioavailability in non
      survivors of sepsis. One may use individual SDMA and ADMA levels to identify
      patients at risk. In view of the pathophysiological role of NO we conclude that
      the vascular system and immune response are most severely affected when SDMA and
      ADMA levels are high.

PMID- 30231909
TI  - Refractory septic shock: our pragmatic approach.
AB  - Despite timely intervention, there exists a small subgroup of patients with
      septic shock who develop progressive multi-organ failure. Seemingly refractory to
      conventional therapy, they exhibit a very high mortality. Such patients are often
      poorly represented in large clinical trials. Consequently, good evidence for
      effective treatment strategies is lacking. In this article, we describe a
      pragmatic, multi-faceted approach to managing patients with refractory septic
      shock based on our experience of toxin-mediated sepsis in a specialist referral
      centre. Many components of this strategy are inexpensive and widely accessible,
      and so may offer an opportunity to improve outcomes in these critically ill
      patients.

PMID- 30231908
TI  - Rapid dissemination of alpha-synuclein seeds through neural circuits in an in
      vivo prion-like seeding experiment.
AB  - Accumulating evidence suggests that the lesions of Parkinson's disease (PD)
      expand due to transneuronal spreading of fibrils composed of misfolded alpha
      synuclein (a-syn), over the course of 5-10 years. However, the precise mechanisms
      and the processes underlying the spread of these fibril seeds have not been
      clarified in vivo. Here, we investigated the speed of a-syn transmission, which
      has not been a focus of previous a-syn transmission experiments, and whether a
      syn pathologies spread in a neural circuit-dependent manner in the mouse brain.
      We injected a-syn preformed fibrils (PFFs), which are seeds for the propagation
      of a-syn deposits, either before or after callosotomy, to disconnect bilateral
      hemispheric connections. In mice that underwent callosotomy before the injection,
      the propagation of a-syn pathology to the contralateral hemisphere was clearly
      reduced. In contrast, mice that underwent callosotomy 24 h after a-syn PFFs
      injection showed a-syn pathology similar to that seen in mice without
      callosotomy. These results suggest that a-syn seeds are rapidly disseminated
      through neuronal circuits immediately after seed injection, in a prion-like
      seeding experiment in vivo, although it is believed that clinical a-syn
      pathologies take years to spread throughout the brain. In addition, we found that
      botulinum toxin B blocked the transsynaptic transmission of a-syn seeds by
      specifically inactivating the synaptic vesicle fusion machinery. This study
      offers a novel concept regarding a-syn propagation, based on the Braak
      hypothesis, and also cautions that experimental transmission systems may be
      examining a unique type of transmission, which differs from the clinical disease
      state.

PMID- 30231910
TI  - A comparison of emotion-focused therapy and cognitive-behavioural therapy in the
      treatment of generalised anxiety disorder: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Generalised anxiety disorder (GAD) is a chronic and debilitating
      condition characterised by high co-morbidity. Alongside pharmacological
      treatment, cognitive behavioural therapy (CBT) is an established psychological
      therapy for GAD. Its effectiveness is limited, however, with only an estimated
      50% of clients presenting in the non-clinical range after a course of treatment.
      Furthermore, not all clients prefer CBT as a psychological therapy. Recently,
      emotion-focused therapy (EFT) was developed for GAD and was tested in an open
      trial with promising results. METHODS/DESIGN: The present research project is a
      feasibility testing randomised controlled trial (RCT) that compares the efficacy
      of EFT with an established treatment for GAD, CBT. Sixty clients presenting in a
      primary care psychology/counselling service will be randomly assigned to one of
      two conditions: EFT or CBT. Outcomes will be assessed using several measures
      (Generalised Anxiety Disorder-7, Generalised Anxiety Disorder Severity Scale,
      Patient Health Questionnaire-9, and Clinical Outcome in Routine Evaluation -
      Outcome Measure). Clients will be assessed prior to and at the end of therapy, as
      well as at 6-month follow-up. On the basis of findings from the initial open EFT
      trial with regard to the optimal length of therapy, it is proposed that therapy
      last between 16 and 20 sessions. DISCUSSION: This study aims to test the
      feasibility of a full comparison RCT. It will test subject recruitment, therapist
      adherence to manualised treatment, and client retention rates. It will also
      provide estimates of comparative outcomes that can inform power calculations for
      a definitive trial. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN52689081 .
      Registered on 24 October 2017.

PMID- 30231911
TI  - The impact of human papillomavirus (HPV) status on functional outcomes and
      quality of life (QOL) after surgical treatment of oropharyngeal carcinoma with
      free-flap reconstruction.
AB  - BACKGROUND: To determine the impact of Human Papillomavirus (HPV) status on
      speech, swallowing, and quality of life (QOL) outcomes after surgical treatment
      of oropharyngeal cancer (OPSCC). METHODS: A retrospective review of a
      prospectively collected database of all patients with OPSCC diagnosed and treated
      from 1998 to 2009. Speech, swallowing, and quality of life data were gathered at
      3 different evaluation points. HPV status was determined using p16 positivity as
      a surrogate marker. Univariate and multivariate statistical analyses were
      performed to identify whether p16 status is a significant predictor of functional
      outcome and QOL. RESULTS: One hundred twelve patients with OPSCC and known p16
      status were treated with primary surgery between 1998 and 2009, with mean age of
      56 years. Out of those patients 63 (56%) were p16 positive. Speech
      intelligibility remained high at 1-year post operation (95.4%). Only 11.5% of the
      patients required a feeding tube at 1 year after surgery to maintain their daily
      caloric requirements and the risk of aspiration after surgery was not significant
      (p = 0.097). There was no statistically or clinically significant difference in
      speech, swallowing ability, swallowing safety and QOL outcomes between p16
      positive and negative OPSCC. CONCLUSIONS: Surgically treated OPSCC patients
      demonstrate excellent swallowing function and can achieve excellent speech
      perception. P16 status may not be predictive of functional outcomes or QOL in
      surgically treated OPSCC.

PMID- 30231912
TI  - The Comparative Effectiveness of Innovative Treatments for Cancer (CEIT-Cancer)
      project: Rationale and design of the database and the collection of evidence
      available at approval of novel drugs.
AB  - BACKGROUND: The available evidence on the benefits and harms of novel drugs and
      therapeutic biologics at the time of approval is reported in publicly available
      documents provided by the US Food and Drug Administration (FDA). We aimed to
      create a comprehensive database providing the relevant information required to
      systematically analyze and assess this early evidence in meta-epidemiological
      research. METHODS: We designed a modular and flexible database of systematically
      collected data. We identified all novel cancer drugs and therapeutic biologics
      approved by the FDA between 2000 and 2016, recorded regulatory characteristics,
      acquired the corresponding FDA approval documents, identified all clinical trials
      reported therein, and extracted trial design characteristics and treatment
      effects. Herein, we describe the rationale and design of the data collection
      process, particularly the organization of the data capture, the identification
      and eligibility assessment of clinical trials, and the data extraction
      activities. DISCUSSION: We established a comprehensive database on the
      comparative effects of drugs and therapeutic biologics approved by the FDA over a
      time period of 17 years for the treatment of cancer (solid tumors and
      hematological malignancies). The database provides information on the clinical
      trial evidence available at the time of approval of novel cancer treatments. The
      modular nature and structure of the database and the data collection processes
      allow updates, expansions, and adaption for a continuous meta-epidemiological
      analysis of novel drugs. The database allows us to systematically evaluate
      benefits and harms of novel drugs and therapeutic biologics. It provides a useful
      basis for meta-epidemiological research on the comparative effects of innovative
      cancer treatments and continuous evaluations of regulatory developments.

PMID- 30231913
TI  - Waves of chromatin modifications in mouse dendritic cells in response to LPS
      stimulation.
AB  - BACKGROUND: The importance of transcription factors (TFs) and epigenetic
      modifications in the control of gene expression is widely accepted. However,
      causal relationships between changes in TF binding, histone modifications, and
      gene expression during the response to extracellular stimuli are not well
      understood. Here, we analyze the ordering of these events on a genome-wide scale
      in dendritic cells in response to lipopolysaccharide (LPS) stimulation. RESULTS:
      Using a ChIP-seq time series dataset, we find that the LPS-induced accumulation
      of different histone modifications follows clearly distinct patterns. Increases
      in H3K4me3 appear to coincide with transcriptional activation. In contrast,
      H3K9K14ac accumulates early after stimulation, and H3K36me3 at later time points.
      Integrative analysis with TF binding data reveals potential links between TF
      activation and dynamics in histone modifications. Especially, LPS-induced
      increases in H3K9K14ac and H3K4me3 are associated with binding by STAT1/2 and
      were severely impaired in Stat1-/- cells. CONCLUSIONS: While the timing of short
      term changes of some histone modifications coincides with changes in
      transcriptional activity, this is not the case for others. In the latter case,
      dynamics in modifications more likely reflect strict regulation by stimulus
      induced TFs and their interactions with chromatin modifiers.

PMID- 30231914
TI  - All-in-one adeno-associated virus delivery and genome editing by Neisseria
      meningitidis Cas9 in vivo.
AB  - BACKGROUND: Clustered, regularly interspaced, short palindromic repeats (CRISPR)
      and CRISPR-associated proteins (Cas) have recently opened a new avenue for gene
      therapy. Cas9 nuclease guided by a single-guide RNA (sgRNA) has been extensively
      used for genome editing. Currently, three Cas9 orthologs have been adapted for in
      vivo genome engineering applications: Streptococcus pyogenes Cas9 (SpyCas9),
      Staphylococcus aureus Cas9 (SauCas9), and Campylobacter jejuni (CjeCas9).
      However, additional in vivo editing platforms are needed, in part to enable a
      greater range of sequences to be accessed via viral vectors, especially those in
      which Cas9 and sgRNA are combined into a single vector genome. RESULTS: Here, we
      present in vivo editing using Neisseria meningitidis Cas9 (NmeCas9). NmeCas9 is
      compact, edits with high accuracy, and possesses a distinct protospacer adjacent
      motif (PAM), making it an excellent candidate for safe gene therapy applications.
      We find that NmeCas9 can be used to target the Pcsk9 and Hpd genes in mice. Using
      tail-vein hydrodynamic-based delivery of NmeCas9 plasmid to target the Hpd gene,
      we successfully reprogram the tyrosine degradation pathway in Hereditary
      Tyrosinemia Type I mice. More importantly, we deliver NmeCas9 with its sgRNA in a
      single recombinant adeno-associated vector (rAAV) to target Pcsk9, resulting in
      lower cholesterol levels in mice. This all-in-one vector yielded > 35% gene
      modification after two weeks of vector administration, with minimal off-target
      cleavage in vivo. CONCLUSIONS: Our findings indicate that NmeCas9 can enable the
      editing of disease-causing loci in vivo, expanding the targeting scope of RNA
      guided nucleases.

PMID- 30231915
TI  - A randomized pragmatic care trial on endovascular acute stroke interventions
      (EASI): criticisms, responses, and ethics of integrating research and clinical
      care.
AB  - BACKGROUND: The Endovascular Acute Stroke Intervention (EASI) trial was conceived
      as a pragmatic care trial, designed to integrate trial methods with clinical
      practice. Reporting the EASI experience was met with objections and criticisms
      during peer review concerning both scientific and ethical issues. Our goal is to
      discuss these criticisms in order to promote the pragmatic approach of care
      trials in outcome-based medical care. METHODS: The comments and criticisms of 11
      reviewers from 5 journals were collected and analyzed. The EASI protocol was also
      compared to the protocols of seven thrombectomy trials using the pragmatic
      explanatory continuum indicator summary (PRECIS). RESULTS: Main criticisms of
      EASI concerned selection criteria that were judged to be too vague and too
      inclusive, brain and vascular imaging methods that were not sufficiently
      prescribed by protocol, lack of blinding of outcome assessment, and lack of
      power. EASI was at the pragmatic end of the spectrum of thrombectomy trials.
      CONCLUSION: The pragmatic care trial methodology is not currently well
      established. More work needs to be done to integrate scientific methods and
      ethical care in the best medical interest of current patients.

PMID- 30231916
TI  - Effects of gait support in patients with spinocerebellar degeneration by a
      wearable robot based on synchronization control.
AB  - BACKGROUND: Spinocerebellar degeneration (SCD) mainly manifests a cerebellar
      ataxic gait, leading to marked postural sway and the risk of falling down. Gait
      support using a wearable robot is expected to be an effective solution to
      maintaining the status quo and/or delaying symptom progression. The aim of this
      study was to evaluate the effects of gait support in patients with SCD by using a
      wearable robotic system called curara (r); while undergoing walking tests.
      METHODS: The curara system assists both the hip and knee joints and supports the
      wearer's rhythmic gait using a synchronization control based on a central pattern
      generator. The system reflects the wearer's intended motion in response to the
      gait support by detecting an interactive force that is generated from slight
      movements of the wearer. The degree of coordinated motion between the robot and
      the wearer can be adjusted by modifying the synchronization gain. In this study,
      we provided gait support using three high-gain conditions (A, B, C) to more
      easily follow the wearer's movement in each joint. The synchronization gains for
      both the hip and knee joints (i.e., Ch and Ck) were set at 0.5 for condition A
      and at 0.4 for condition B. Condition C had different gains for the hip and knee
      joints (i.e., Ch=0.4 and Ck=0.5). With the walking test, we assessed the effects
      of the gait support provided by the curara system on walking smoothness (measured
      using the harmonic ratio: HR) and spatiotemporal parameters (gait speed, stride
      length, cadence) in SCD patients (n=12). We compared the performance between the
      three high-gain conditions and without assistance from the robot. RESULTS: Under
      condition C, the HRs in the anteroposterior, mediolateral, and vertical
      directions (HR-AP, HR-ML, and HR-V) were especially high compared with those
      under conditions A and B. The results of the statistical analyses using repeated
      measures analysis of variance followed by Tukey's test showed that gait support
      with condition C results in a statistically significant increase in the HR-AP
      (2.04 +/-0.52; p=0.025) and HR-V (2.06 +/-0.37; p=0.032) when compared with
      walking without assistance from the system. In contrast, the gait speed, stride
      length, and cadence under condition C were no major changes in most patients,
      compared with the patient's walking without assistance. CONCLUSIONS: The
      significantly increased HR indicates that gait support under condition C achieved
      smoother walking than when not wearing the power unit of the system.
      Consequently, we suggest that gait support using the curara system has the
      potential to improve walking smoothness in patients with SCD.

PMID- 30231917
TI  - Surveying knowledge, practice and attitudes towards intervention fidelity within
      trials of complex healthcare interventions.
AB  - BACKGROUND: Intervention fidelity is the degree to which interventions have been
      implemented as intended by their developers. Assessing fidelity is crucial for
      accurate interpretation of intervention effectiveness, but fidelity is often
      poorly addressed within trials of complex healthcare interventions. The reasons
      for this are unclear, and information on the use of methods to enhance and assess
      fidelity in trials of complex interventions remains insufficient. This study
      aimed to explore the knowledge, practice and attitudes towards intervention
      fidelity amongst researchers, triallists and healthcare professionals involved
      with the design and conduct of trials of complex healthcare interventions.
      METHODS: An online survey consisting of closed and open-ended questions exploring
      four sections (Demographics, Fidelity knowledge, Practice and Attitudes) was
      conducted. This was an opportunistic sample of individuals with experience of
      direct involvement in trials of complex healthcare interventions (e.g.
      design/development, conduct, evaluation). RESULTS: Data from 264 participants
      representing 15 countries were analysed. The majority (65.9%, n = 174) of
      participants identified themselves as 'Researchers'. The majority of participants
      were familiar with the term "intervention fidelity" (69.7%, n = 184) and
      indicated that fidelity is important (89.7%, n = 236). Mean self-reported
      understanding of fidelity was moderate. Although 68% (n = 182) had previously
      used strategies to assess (e.g. audio/video-recording sessions) and enhance (e.g.
      training manual) fidelity in trials of complex interventions, only a limited
      proportion of participants indicated always reporting these strategies in
      subsequent publications (30.9%, n = 56). Poor knowledge or understanding was the
      most commonly cited barrier to addressing intervention fidelity in trials (77.4%,
      n = 202). Over half of respondents (52.1%, n = 137) had never completed specific
      fidelity training or research, and the vast majority (89.7%, n = 236) would
      welcome specific training in this area. CONCLUSION: Despite good awareness of
      intervention fidelity and its importance, poor knowledge and understanding
      appears to be a key factor limiting how intervention fidelity is addressed in
      trials of complex interventions. Participants identified a need for further
      training and education in this area. Additionally, clarification of the
      terminology, definition and components of intervention fidelity would facilitate
      better understanding of the concept. A discrepancy between participants' use of
      fidelity strategies and subsequent reporting raises concerns around inadequate
      fidelity reporting in the trials literature.

PMID- 30231918
TI  - The effect of Neuroligin-2 absence on sleep architecture and
      electroencephalographic activity in mice.
AB  - Sleep disorders are comorbid with most psychiatric disorders, but the link
      between these is not well understood. Neuroligin-2 (NLGN2) is a cell adhesion
      molecule that plays roles in synapse formation and neurotransmission. Moreover,
      NLGN2 has been associated with psychiatric disorders, but its implication in
      sleep remains underexplored. In the present study, the effect of Nlgn2 knockout
      (Nlgn2-/-) on sleep architecture and electroencephalographic (EEG) activity in
      mice has been investigated. The EEG and electromyogram (EMG) were recorded in
      Nlgn2-/- mice and littermates for 24 h from which three vigilance states (i.e.,
      wakefulness, rapid eye movement [REM] sleep, non-REM [NREM] sleep) were visually
      identified. Spectral analysis of the EEG was performed for the three states.
      Nlgn2-/- mice showed more wakefulness and less NREM and REM sleep compared to
      wild-type (Nlgn2+/+) mice, especially during the dark period. This was
      accompanied by changes in the number and duration of individual episodes of
      wakefulness and sleep, indexing changes in state consolidation, as well as
      widespread changes in EEG spectral activity in all states. Abnormal
      'hypersynchronized' EEG events have also been observed predominantly in Nlgn2-/-
      mice. These events were mainly observed during wakefulness and REM sleep. In
      addition, Nlgn2-/- mice showed alterations in the daily time course of NREM sleep
      delta (1-4 Hz) activity, pointing to modifications in the dynamics of sleep
      homeostasis. These data suggest that NLGN2 participates in the regulation of
      sleep duration as well as EEG activity during wakefulness and sleep.

PMID- 30231919
TI  - Revisiting the infectivity and pathogenicity of Cryptosporidium avium provides
      new information on parasitic sites within the host.
AB  - BACKGROUND: Cryptosporidium spp. are protozoans that cause diarrheal illness in
      humans and animals, including birds, worldwide. The present study was aimed to
      revisit the infectivity and pathogenicity of C. avium, recently considered to be
      a valid avian-infecting species of Cryptosporidium, and foster further
      understanding of its biological characteristics. RESULTS: Results showed that no
      Cryptosporidium oocysts were detected in the feces of experimentally inoculated
      BALB/c mice, Mongolian gerbils, quail or budgerigars within 30 days post
      infection (dpi). Oocysts were first detected in feces of 3-day-old and 40-day-old
      hens at 8 and 9 dpi, respectively. In ducks infected with C. avium, oocysts were
      first detected at 9 dpi. Oocysts of infected animals were studied using a nested
      polymerase chain reaction (PCR) technique for the SSU rRNA gene, actin gene,
      HSP70 gene and Cryptosporidium oocyst wall protein gene (COWP) detection.
      Restriction fragment length polymorphism (RFLP), using SspI and VspI restriction
      enzymes, was carried out to genotype the species and obtained amplification
      products were sequenced. Cryptosporidium developmental stages were found in the
      longitudinal plica of the bursa fabricii (BF) of hens, with high levels observed
      in histological sections and scanning electron microscopy. No pathological
      changes were observed. CONCLUSIONS: These findings indicate that the bursa
      fabricii may be the primary site of C. avium infection. More biological data are
      needed to support the establishment of new species and contribute to the taxonomy
      of Cryptosporidium.

PMID- 30231920
TI  - Focused scores enable reliable discrimination of small differences in steatosis.
AB  - BACKGROUND: Automated image analysis enables quantitative measurement of
      steatosis in histological images. However, spatial heterogeneity of steatosis can
      make quantitative steatosis scores unreliable. To improve the reliability, we
      have developed novel scores that are "focused" on steatotic tissue areas.
      METHODS: Focused scores use concepts of tile-based hotspot analysis in order to
      compute statistics about steatotic tissue areas in an objective way. We evaluated
      focused scores on three data sets of images of rodent liver sections exhibiting
      different amounts of dietary-induced steatosis. The same evaluation was conducted
      with the standard steatosis score computed by most image analysis methods.
      RESULTS: The standard score reliably discriminated large differences in steatosis
      (intraclass correlation coefficient ICC = 0.86), but failed to discriminate small
      (ICC = 0.54) and very small (ICC = 0.14) differences. With an appropriate tile
      size, mean-based focused scores reliably discriminated large (ICC = 0.92), small
      (ICC = 0.86) and very small (ICC = 0.83) differences. Focused scores based on
      high percentiles showed promise in further improving the discrimination of very
      small differences (ICC = 0.93). CONCLUSIONS: Focused scores enable reliable
      discrimination of small differences in steatosis in histological images. They are
      conceptually simple and straightforward to use in research studies.

PMID- 30231921
TI  - A metagenomics roadmap to the uncultured genome diversity in hypersaline soda
      lake sediments.
AB  - BACKGROUND: Hypersaline soda lakes are characterized by extreme high soluble
      carbonate alkalinity. Despite the high pH and salt content, highly diverse
      microbial communities are known to be present in soda lake brines but the
      microbiome of soda lake sediments received much less attention of
      microbiologists. Here, we performed metagenomic sequencing on soda lake sediments
      to give the first extensive overview of the taxonomic diversity found in these
      complex, extreme environments and to gain novel physiological insights into the
      most abundant, uncultured prokaryote lineages. RESULTS: We sequenced five
      metagenomes obtained from four surface sediments of Siberian soda lakes with a pH
      10 and a salt content between 70 and 400 g L-1. The recovered 16S rRNA gene
      sequences were mostly from Bacteria, even in the salt-saturated lakes. Most OTUs
      were assigned to uncultured families. We reconstructed 871 metagenome-assembled
      genomes (MAGs) spanning more than 45 phyla and discovered the first extremophilic
      members of the Candidate Phyla Radiation (CPR). Five new species of CPR were
      among the most dominant community members. Novel dominant lineages were found
      within previously well-characterized functional groups involved in carbon,
      sulfur, and nitrogen cycling. Moreover, key enzymes of the Wood-Ljungdahl pathway
      were encoded within at least four bacterial phyla never previously associated
      with this ancient anaerobic pathway for carbon fixation and dissimilation,
      including the Actinobacteria. CONCLUSIONS: Our first sequencing effort of
      hypersaline soda lake sediment metagenomes led to two important advances. First,
      we showed the existence and obtained the first genomes of haloalkaliphilic
      members of the CPR and several hundred other novel prokaryote lineages. The soda
      lake CPR is a functionally diverse group, but the most abundant organisms in this
      study are likely fermenters with a possible role in primary carbon degradation.
      Second, we found evidence for the presence of the Wood-Ljungdahl pathway in many
      more taxonomic groups than those encompassing known homo-acetogens, sulfate
      reducers, and methanogens. Since only few environmental metagenomics studies have
      targeted sediment microbial communities and never to this extent, we expect that
      our findings are relevant not only for the understanding of haloalkaline
      environments but can also be used to set targets for future studies on marine and
      freshwater sediments.

PMID- 30231922
TI  - HSCs-derived COMP drives hepatocellular carcinoma progression by activating
      MEK/ERK and PI3K/AKT signaling pathways.
AB  - BACKGROUND: Cartilage oligomeric matrix protein (COMP) is known to promote
      fibrosis in skin, lung and liver. Emerging evidence shows that COMP plays
      critical roles in tumor development, including breast cancer, colon cancer and
      hepatocellular carcinoma (HCC). Nevertheless, the role of COMP in HCC
      proliferation and metastasis and its underlying mechanisms remain fully unclear.
      METHODS: Serum COMP was determined by ELISA. Cell Counting Kit-8 and plate colony
      formation were performed to evaluate cell proliferation. Wound healing and
      transwell assays were used to determine migration and invasion of HCC cells.
      Western blotting and immunofluorescence were carried out for detection of
      epithelial-to-mesenchymal transition (EMT) markers and MMPs in HCC cells. The in
      vivo role of COMP was evaluated using mouse models. We also measured effects of
      hepatic stellate cells (HSCs)-conditioned medium (CM) on HCC progression using
      transwell coculture system. RESULTS: Here, we found that serum COMP levels in HCC
      patients were significantly higher than those in healthy controls. Accordingly,
      high serum COMP levels in HCC patients significantly correlated with malignant
      clinical characteristics and poor clinical outcomes. Next, we investigated that
      recombinant human COMP protein (rCOMP) treatment resulted in increased abilities
      of proliferation, invasion and migration of HCC cells. Furthermore, rCOMP
      treatment enhanced proliferative and metastatic colonization of HCC cells in
      vivo. Mechanistically, CD36 receptor played an essential role in COMP-mediated
      HCC cell proliferation and metastasis. Functionally, COMP/CD36 signaling caused
      phosphorylation of ERK and AKT, resulting in the upregulation of tumor
      progressive genes such as EMT markers, MMP-2/9, Slug and Twist in HCC cells.
      Interestingly, we revealed that COMP was secreted by HSCs. CM of LX2 cells with
      COMP knockdown showed weaker effects on the activation of MEK/ERK and PI3K/AKT
      signaling pathways in HCC cells compared to control CM. CONCLUSIONS: Our findings
      indicated that HSCs-derived COMP collaborated with CD36 and subsequently played
      an essential role in MEK/ERK and PI3K/AKT-mediated HCC progression. COMP might
      act as a promising target for the diagnosis and treatment of aggressive HCC.

PMID- 30231923
TI  - Early vascular parameters in the micro- and macrocirculation in type 2 diabetes.
AB  - BACKGROUND: Diabetes converts from a metabolic disorder into a predominantly
      vascular disease, once its duration extends over several years or/and when
      additional cardiovascular risk factors such as hypertension coexist. In a cross
      sectional analysis we analyzed various vascular parameters in the renal, retinal
      and systemic circulation, with the goal to identify which vascular parameter of
      early organ damage is the earliest that can be clinically detected. METHODS: In
      111 patients with type 2 diabetes (T2DM) (off any anti-diabetic medication for at
      least 4 weeks) and 54 subjects without T2DM we compared various parameters of
      early vascular remodeling in the same patient: urinary albumin creatinine ratio
      ([UACR], early morning spot urine) and estimated glomerular filtration rate
      (eGFR), retinal capillary flow (RCF) and intercapillary distance (ICD) as
      parameters of capillary rarefaction, wall-to-lumen ratio (WLR) of the retinal
      arterioles [all assessed by Scanning Laser Doppler Flowmetry], and central
      systolic pressure (cSBP) and central pulse pressure (cPP) [measured by pulse wave
      analysis, Syphygmocor] both reflecting vascular stiffness of large arteries.
      RESULTS: Compared to subjects without T2DM, patients with T2DM (diabetes
      duration: median 48 months, interquartile range 24-88 months) were older (59.8 +/
      7.3 vs 43.4 +/- 12.9 years, p < 0.001), more females (33.3 vs 20.4%, p < 0.001),
      but 24-h systolic and diastolic blood pressure did not differ between the two
      groups. The analysis adjusted for age, gender and cardiovascular risk factors
      revealed that ICD (23.9 +/- 5.1 vs 20.8 +/- 3.5 um, p value = 0.001) and cPP
      (41.8 +/- 11.7 vs 34.8 +/- 10.6 mmHg, p value < 0.001) were significantly higher
      and eGFR (91.7 +/- 9.9 vs 95.9 +/- 17.3 ml/min/1.73 m2, p value < 0.001) was
      significantly lower in patients with T2DM than in subjects without T2DM.
      CONCLUSION: These data suggest that at similar blood pressure capillary
      rarefaction in the retinal circulation (ICD), decreased eGFR in the renal
      circulation and increased central pulse pressure (cPP) of large arteries are
      earlier detectable than other vascular remodeling parameters of the micro- (WLR,
      RCF, UACR) and macrocirculation (cSBP) in patients with T2DM. Trial registration
      Trial registration number: NCT02471963, Date of registration: June 15, 2015,
      retrospectively registered; Trial registration number: NCT01319357, Date of
      registration: March 21, 2011, retrospectively registered; Trial registration
      number: NCT02383238, Date of registration: March 9, 2015, retrospectively
      registered; Trial registration number: NCT00152698, Date of registration:
      September 9, 2005, prospectively registered; Trial registration number:
      NCT00136188, Date of registration: August 26, 2005, prospectively registered.

PMID- 30231924
TI  - The effects of ultrasound exposure on P-glycoprotein-mediated multidrug
      resistance in vitro and in vivo.
AB  - BACKGROUND: Multidrug resistance (MDR) is often responsible for the failure of
      chemotherapy treatment, and current strategies for cancer MDR are not adequately
      satisfying as to their efficacy and safety. In this study, we sought to determine
      the anti-MDR effects of ultrasound (US) irradiation and its underlying mechanisms
      against drug-resistance. METHODS: MDR variant MCF-7/ADR cell lines and
      endothelial cell lines were used to determine the appropriate ultrasound
      intensity for in vitro experiments. MCF-7/ADR cell and HEPG2/ADM cells were used
      to assess the anti-MDR effect of US irradiation. Intracellular adriamycin (ADM)
      accumulation, Cell viability, cell proliferation and cell apoptosis were
      evaluated after ADM + US treatment or ADM treatment alone. MCF-7/ADR xenograft
      mice were used to investigate the appropriate ultrasound intensity for in vivo
      experiments and its effect on the long-term prognosis. Underlining mechanisms by
      which ultrasound exposure reversing MDR phenotype were investigated both in vitro
      and in vivo. RESULTS: Combination of ADM and 0.74 W/cm2 US irradiation enhanced
      ADM intracellular concentration and nuclear accumulation in MCF-7/ADR and
      HEPG2/ADM cells, compared to those treated with ADM alone. Enhanced cellular ADM
      uptake and nuclei localization was associated with increased cytotoxicity of ADM
      to ADM-resistant cells, lower ADM-resistant cell viability and proliferative cell
      ratio, and higher apoptotic cell ratio. More importantly, US exposure increased
      the effectiveness of ADM to inhibit tumor growth in MCF-7/ADR xenograft mice.
      Mechanistically, US exposure promoted ADM accumulation in MDR cells mainly
      through down-regulation of P-glycoprotein (P-gp), which is dependent on US
      induced intracellular reactive oxygen species (ROS) production. US-induced
      oxidative stress promoted miR-200c-3p and miR-34a-3p expression by forming miR
      200c/34a/ZEB1 double-negative feedback loop. Finally, US-induced miR-200c/34a
      overexpression decreased P-gp expression and reversed MDR phenotype. CONCLUSION:
      US irradiation could reverse MDR phenotype by activating ROS-ZEB1-miR200c/34a-P
      gp signal pathway. Our findings offer a new and promising strategy for
      sensitizing cells to combat MDR and to improve the therapeutic index of
      chemotherapy.

PMID- 30231926
TI  - Thiamine deficiency contributes to synapse and neural circuit defects.
AB  - BACKGROUND: The previous studies have demonstrated the reduction of thiamine
      diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain
      glucose hypometabolism, which is considered as a neurodegenerative index of AD
      and closely correlates with the degree of cognitive impairment. The reduction of
      thiamine diphosphate may contribute to the dysfunction of synapses and neural
      circuits, finally leading to cognitive decline. RESULTS: To demonstrate this
      hypothesis, we established abnormalities in the glucose metabolism utilizing
      thiamine deficiency in vitro and in vivo, and we found dramatically reduced
      dendrite spine density. We further detected lowered excitatory neurotransmission
      and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in
      vitro. Importantly, via treatment with benfotiamine, Abeta induced spines density
      decrease was considerably ameliorated. CONCLUSIONS: These results revealed that
      thiamine deficiency contributed to synaptic dysfunction which strongly related to
      AD pathogenesis. Our results provide new insights into pathogenesis of synaptic
      and neuronal dysfunction in AD.

PMID- 30231925
TI  - The role of plasmalemma vesicle-associated protein in pathological breakdown of
      blood-brain and blood-retinal barriers: potential novel therapeutic target for
      cerebral edema and diabetic macular edema.
AB  - Breakdown of the blood-brain barrier (BBB) or inner blood-retinal barrier (BRB),
      induced by pathologically elevated levels of vascular endothelial growth factor
      (VEGF) or other mediators, can lead to vasogenic edema and significant clinical
      problems such as neuronal morbidity and mortality, or vision loss. Restoration of
      the barrier function with corticosteroids in the brain, or by blocking VEGF in
      the eye are currently the predominant treatment options for brain edema and
      diabetic macular edema, respectively. However, corticosteroids have side effects,
      and VEGF has important neuroprotective, vascular protective and wound healing
      functions, implying that long-term anti-VEGF therapy may also induce adverse
      effects. We postulate that targeting downstream effector proteins of VEGF and
      other mediators that are directly involved in the regulation of BBB and BRB
      integrity provide more attractive and safer treatment options for vasogenic
      cerebral edema and diabetic macular edema. The endothelial cell-specific protein
      plasmalemma vesicle-associated protein (PLVAP), a protein associated with trans
      endothelial transport, emerges as candidate for this approach. PLVAP is expressed
      in a subset of endothelial cells throughout the body where it forms the
      diaphragms of caveolae, fenestrae and trans-endothelial channels. However, PLVAP
      expression in brain and eye barrier endothelia only occurs in pathological
      conditions associated with a compromised barrier function such as cancer,
      ischemic stroke and diabetic retinopathy. Here, we discuss the current
      understanding of PLVAP as a structural component of endothelial cells and
      regulator of vascular permeability in health and central nervous system disease.
      Besides providing a perspective on PLVAP identification, structure and function,
      and the regulatory processes involved, we also explore its potential as a novel
      therapeutic target for vasogenic cerebral edema and retinal macular edema.

PMID- 30231927
TI  - Oligodendrogliomas, IDH-mutant and 1p/19q-codeleted, arising during teenage years
      often lack TERT promoter mutation that is typical of their adult counterparts.

PMID- 30231928
TI  - Deletion of the microtubule-associated protein 6 (MAP6) results in skeletal
      muscle dysfunction.
AB  - BACKGROUND: The skeletal muscle fiber has a specific and precise intracellular
      organization which is at the basis of an efficient muscle contraction.
      Microtubules are long known to play a major role in the function and organization
      of many cells, but in skeletal muscle, the contribution of the microtubule
      cytoskeleton to the efficiency of contraction has only recently been studied. The
      microtubule network is dynamic and is regulated by many microtubule-associated
      proteins (MAPs). In the present study, the role of the MAP6 protein in skeletal
      muscle organization and function has been studied using the MAP6 knockout mouse
      line. METHODS: The presence of MAP6 transcripts and proteins was shown in mouse
      muscle homogenates and primary culture using RT-PCR and western blot. The in vivo
      evaluation of muscle force of MAP6 knockout (KO) mice was performed on
      anesthetized animals using electrostimulation coupled to mechanical measurement
      and multimodal magnetic resonance. The impact of MAP6 deletion on microtubule
      organization and intracellular structures was studied using immunofluorescent
      labeling and electron microscopy, and on calcium release for muscle contraction
      using Fluo-4 calcium imaging on cultured myotubes. Statistical analysis was
      performed using Student's t test or the Mann-Whitney test. RESULTS: We
      demonstrate the presence of MAP6 transcripts and proteins in skeletal muscle.
      Deletion of MAP6 results in a large number of muscle modifications: muscle
      weakness associated with slight muscle atrophy, alterations of microtubule
      network and sarcoplasmic reticulum organization, and reduction in calcium
      release. CONCLUSION: Altogether, our results demonstrate that MAP6 is involved in
      skeletal muscle function. Its deletion results in alterations in skeletal muscle
      contraction which contribute to the global deleterious phenotype of the MAP6 KO
      mice. As MAP6 KO mouse line is a model for schizophrenia, our work points to a
      possible muscle weakness associated to some forms of schizophrenia.

PMID- 30231929
TI  - Metatranscriptomics reveals a differential temperature effect on the structural
      and functional organization of the anaerobic food web in rice field soil.
AB  - BACKGROUND: The expected increase in global surface temperature due to climate
      change may have a tremendous effect on the structure and function of the
      anaerobic food web in flooded rice field soil. Here, we used the
      metatranscriptomic analysis of total RNA to gain a system-level understanding of
      this temperature effect on the methanogenic food web. RESULTS: Mesophilic (30 
      degrees C) and thermophilic (45  degrees C) food web communities had a modular
      structure. Family-specific rRNA dynamics indicated that each network module
      represents a particular function within the food webs. Temperature had a
      differential effect on all the functional activities, including polymer
      hydrolysis, syntrophic oxidation of key intermediates, and methanogenesis. This
      was further evidenced by the temporal expression patterns of total bacterial and
      archaeal mRNA and of transcripts encoding carbohydrate-active enzymes (CAZymes).
      At 30  degrees C, various bacterial phyla contributed to polymer hydrolysis, with
      Firmicutes decreasing and non-Firmicutes (e.g., Bacteroidetes, Ignavibacteriae)
      increasing with incubation time. At 45  degrees C, CAZyme expression was solely
      dominated by the Firmicutes but, depending on polymer and incubation time, varied
      on family level. The structural and functional community dynamics corresponded
      well to process measurements (acetate, propionate, methane). At both
      temperatures, a major change in food web functionality was linked to the
      transition from the early to late stage. The mesophilic food web was
      characterized by gradual polymer breakdown that governed acetoclastic
      methanogenesis (Methanosarcinaceae) and, with polymer hydrolysis becoming the
      rate-limiting step, syntrophic propionate oxidation (Christensenellaceae,
      Peptococcaceae). The thermophilic food web had two activity stages characterized
      first by polymer hydrolysis and followed by syntrophic oxidation of acetate
      (Thermoanaerobacteraceae, Heliobacteriaceae, clade OPB54). Hydrogenotrophic
      Methanocellaceae were the syntrophic methanogen partner, but their population
      structure differed between the temperatures. Thermophilic temperature promoted
      proliferation of a new Methanocella ecotype. CONCLUSIONS: Temperature had a
      differential effect on the structural and functional continuum in which the
      methanogenic food web operates. This temperature-induced change in food web
      functionality may not only be a near-future scenario for rice paddies but also
      for natural wetlands in the tropics and subtropics.

PMID- 30231930
TI  - Clinical pitfalls in the diagnosis of segmental overgrowth syndromes: a child
      with the c.2740G > A mutation in PIK3CA gene.
AB  - BACKGROUND: Overgrowth syndromes are known as a heterogeneous group of conditions
      characterized by a generalized or segmental, symmetric or asymmetric, overgrowth
      that may involve several tissues. These disorders, which present a wide range of
      phenotypic variability, are often caused by mosaic somatic mutations in the genes
      associated with the PI3K/AKT/mTOR cellular pathway, a signaling cascade that
      plays a key role in cellular growth. Overgrowth syndromes are frequently
      misdiagnosed. Given that they are also associated to an increased oncologic risk,
      it is important to distinguish the clinical characteristic of these disorders
      since the first months of life. CASE PRESENTATION: We report the case of a seven
      year-old male child with macrocephaly and right lateralized overgrowth, reported
      from birth. The patient arrived to our attention after an initial diagnosis of
      isolated benign macrocephaly was formulated at the age of 12 months. Afterwards,
      the child presented a moderate intellectual disability and pain episodes at right
      lower limb. We repeated a brain Magnetic Resonance Imaging that revealed
      ventriculomegaly, cerebellar tonsillar ectopia, a markedly thick corpus callosum,
      and white matter abnormalities. The diagnosis of segmental overgrowth syndrome
      was formulated according to the clinical presentation and confirmed by the
      finding of the variant c.2740G > A in the gene PIK3CA presented in somatic
      mosaicism. CONCLUSIONS: Our patient is the first children with the c.2740G > A
      variant in PIK3CA gene reported in Italy. We underline the importance of the
      genotype-phenotype correlation in the diagnostic process of overgrowth syndromes
      and emphasize the strict correlation between the mutation c.2740G > A in the
      PIK3CA gene and the Megalencephaly-Capillary Malformation syndrome phenotype.

PMID- 30231931
TI  - Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical
      development.
AB  - Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets
      vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor
      receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit.
      Compared to the effect of placebo, it improved both progression-free survival
      (PFS) and overall survival (OS) in a phase III trial in patients with advanced
      non-small-cell lung cancer (NSCLC), despite progression of the cancer after two
      lines of prior treatments. Recently, the China Food and Drug Administration
      (CFDA) approved single agent anlotinib as a third-line treatment for patients
      with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that
      anlotinib significantly prolonged the median PFS in patients with advanced soft
      tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with
      advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC).
      The tolerability profile of anlotinib is similar to that of other tyrosine kinase
      inhibitors that target VEGFR and other tyrosine kinase-mediated pathways;
      however, anlotinib has a significantly lower incidence of grade 3 or higher side
      effects compared to that of sunitinib. We review the rationale, clinical
      evidence, and future perspectives of anlotinib for the treatment of multiple
      cancers.

PMID- 30231932
TI  - Indirect costs and public finance consequences of heart failure in Poland, 2012
      2015.
AB  - BACKGROUND: As a consequence of unfavourable epidemiological trends and the
      development of disease management, the economic aspects of heart failure (HF)
      have become more and more important. The costs of treatment (direct costs) appear
      to be the most frequently addressed topic in the economic research on HF;
      however, less is known about productivity losses (indirect costs) and the public
      finance burden attributable to the disease. Therefore, the aim of this study was
      to estimate the indirect costs and public finance consequences of HF in Poland in
      the period 2012-2015. METHODS: The study uses a societal perspective and a
      prevalence-based top-down approach to estimate the following components of HF
      indirect costs: absenteeism of the sick and their caregivers, presenteeism of the
      sick, disability, and premature mortality. The human capital method has been
      chosen to identify the value of productivity losses attributable to HF and the
      public finance consequences of the disease. Deterministic sensitivity analysis
      was performed to assess the robustness of the results. RESULTS: The total
      indirect costs of HF in Poland were ?871.9 million in 2012, and they increased to
      ?945.3 million in 2015. In the period investigated, these costs accounted for
      0.212-0.224% of GDP, an equivalent of 22.63?-24.59? per capita. Mortality proved
      to be the main driver of productivity losses, with 59.3-63.4% of the total costs
      depending on year, followed by presenteeism (21.1-22.5%), disability (11.1-14.2%)
      and the sick's absenteeism (3.3-4.0%). The cost of caregivers' absenteeism was
      unimportant. The social insurance expenditure for benefits associated with HF
      accounted for ?40.7 million in 2012 and ?45.6 million in 2015 (0.56-0.59%
      expenditure for all diseases). The potential public revenue losses associated
      with HF were ?262.7-?287.9 million. Sensitivity analysis showed that the costs
      varied by - 12.1% to + 28.8% depending on the model parameter values. CONCLUSION:
      HF is a substantial burden on the economy and public finance in Poland. By
      confronting the disease more effectively, the length and quality of life for
      those affected by HF could be improved, but society as a whole could also benefit
      from the increased economic output.

PMID- 30231933
TI  - Pathobiology of Avian avulavirus 1: special focus on waterfowl.
AB  - Avian avulaviruses serotype 1 (abbreviated as APMV-1 for the historical name
      avian paramyxovirus 1) are capable of infecting a wide spectrum of avian species
      with variable clinical symptoms and outcomes. Ease of transmission has allowed
      the virus to spread worldwide with varying degrees of virulence depending upon
      the virus strain and host species. The emergence of new virulent genotypes from
      global epizootics, and the year-to-year genomic changes in low and high virulence
      APMV-1 imply that distinct genotypes of APMV-1 are simultaneously evolving at
      different geographic locations across the globe. This vast genomic diversity may
      be favoured by large variety of avian species susceptibility to APMV-1 infection,
      and by the availability of highly mobile wild birds. It has long been considered
      that waterfowls are not sensitive to APMV-1 and are unable to show any clinical
      signs, however, outbreaks from the 90's contradict these concepts. The APMV-1
      isolates are increasingly reported from the waterfowl. Waterfowl have strong
      innate immune responses, which minimize the impact of virus infection, however,
      are unable to prevent the viral shedding. Numerous APMV-1 are carried by domestic
      waterfowl intermingling with terrestrial poultry. Therefore, commercial ducks and
      geese should be vaccinated against APMV-1 to minimize the virus shedding and for
      the prevention the transmission. Genetic diversity within APMV-1 demonstrates the
      need for continual monitoring of viral evolution and periodic updates of vaccine
      seed-strains to achieve efficient control and eradication of APMV-1 in
      waterfowls.

PMID- 30231934
TI  - Audience segmentation to disseminate behavioral health evidence to legislators:
      an empirical clustering analysis.
AB  - BACKGROUND: Elected officials (e.g., legislators) are an important but
      understudied population in dissemination research. Audience segmentation is
      essential in developing dissemination strategies that are tailored for
      legislators with different characteristics, but sophisticated audience
      segmentation analyses have not been conducted with this population. An empirical
      clustering audience segmentation study was conducted to (1) identify behavioral
      health (i.e., mental health and substance abuse) audience segments among US state
      legislators, (2) identify legislator characteristics that are predictive of
      segment membership, and (3) determine whether segment membership is predictive of
      support for state behavioral health parity laws. METHODS: Latent class analysis
      (LCA) was used. Data were from a multi-modal (post-mail, e-mail, telephone)
      survey of state legislators fielded in 2017 (N = 475). Nine variables were
      included in the LCA (e.g., perceptions of behavioral health treatment
      effectiveness, mental illness stigma). Binary logistic regression tested
      associations between legislator characteristics (e.g., political party, gender,
      ideology) and segment membership. Multi-level logistic regression assessed the
      predictive validity of segment membership on support for parity laws. A name was
      developed for each segment that captured its most salient features. RESULTS:
      Three audience segments were identified. Budget-oriented skeptics with stigma
      (47% of legislators) had the least faith in behavioral health treatment
      effectiveness, had the most mental illness stigma, and were most influenced by
      budget impact. This segment was predominantly male, Republican, and ideologically
      conservative. Action-oriented supporters (24%) were most likely to have
      introduced a behavioral health bill, most likely to identify behavioral health
      issues as policy priorities, and most influenced by research evidence. This was
      the most politically and ideologically diverse segment. Passive supporters (29%)
      had the greatest faith in treatment effectiveness and the least stigma, but were
      also least likely to have introduced a behavioral health bill. Segment membership
      was a stronger predictor of support for parity laws than almost all other
      legislator characteristics. CONCLUSIONS: State legislators are a heterogeneous
      audience when it comes to behavioral health. There is a need to develop and test
      behavioral health evidence dissemination strategies that are tailored for
      legislators in different audience segments. Empirical clustering approaches to
      audience segmentation are a potentially valuable tool for dissemination science.

PMID- 30231935
TI  - Is sperm morphology functionally related to sperm swimming ability? A case study
      in a wild passerine bird with male hierarchies.
AB  - BACKGROUND: Sexual selection continues after copulation via either sperm
      competition or cryptic female choice, and favors sperm traits that maximize sperm
      competitiveness. Both sperm swimming velocity and longevity are important
      determinants of the outcome of sperm competition. Theoretically, sperm morphology
      can influence sperm velocity at least in three different non-exclusive ways: (i)
      longer sperm may generate more propelling thrust, (ii) bigger midpieces may
      produce more energy, and/or (iii) larger flagella or mid-pieces relative to the
      head size may compensate for the drag forces around the head. A growing number of
      studies have investigated the relationship of sperm morphology with sperm
      performance, which remains equivocal at both the inter- and intra-specific
      levels. Here, we used House Sparrows to test the functional relationship between
      sperm morphology with sperm velocity and longevity. Based on a previous study
      showing that sperm swimming ability covaries with social rank, we predicted that 
      if a functional relationship exists-1) sperm morphology should differ across
      social ranks, and 2) correlations between sperm morphology and sperm velocity
      and/or sperm longevity should be constant across social ranks. RESULTS: We found
      no differences in sperm morphology across social ranks. Moreover, we found that
      sperm morphology may be correlated with sperm velocity, but such relationship
      varied across social ranks. This result contradicts the hypothesis of a
      functional relationship between sperm morphology and sperm performance. Finally,
      after experimentally manipulating social ranks, we observed that relationships
      between sperm morphology and sperm velocity and/or sperm longevity disappeared or
      changed direction. CONCLUSIONS: We suggest that in species with internal
      fertilization, while sperm morphology is likely constrained by the morphology of
      the female sperm storage organs, selection may act upon physiological traits that
      enhance sperm performance. Hence, these two selection forces could decouple sperm
      performance from sperm morphology.

PMID- 30231936
TI  - Genome-wide SNP analyses reveal high gene flow and signatures of local adaptation
      among the scalloped spiny lobster (Panulirus homarus) along the Omani coastline.
AB  - BACKGROUND: The scalloped spiny lobster (Panulirus homarus) is a popular seafood
      commodity worldwide and an important export item from Oman. Annual catches in
      commercial fisheries are in serious decline, which has resulted in calls for the
      development of an integrated stock management approach. In Oman, the scalloped
      spiny lobster is currently treated as a single management unit (MU) or stock and
      there is an absence of information on the genetic population structure of the
      species that can inform management decisions, particularly at a fine-scale level.
      This work is the first to identify genome-wide single nucleotide polymorphisms
      (SNPs) for P. homarus using Diversity Arrays Technology sequencing (DArT-seq) and
      to elucidate any stock structure in the species. RESULTS: After stringent
      filtering, 7988 high utility SNPs were discovered and used to assess the genetic
      diversity, connectivity and structure of P. homarus populations from Al
      Ashkharah, Masirah Island, Duqm, Ras Madrakah, Haitam, Ashuwaymiyah, Mirbat and
      Dhalkut landing sites. Pairwise FST estimates revealed low differentiation among
      populations (pairwise FST range = - 0.0008 - 0.0021). Analysis of genetic
      variation using putatively directional FST outliers (504 SNPs) revealed higher
      and significant pairwise differentiation (p < 0.01) for all locations, with
      Ashuwaymiyah being the most diverged population (Ashuwaymiyah pairwise FST range
      = 0.0288-0.0736). Analysis of population structure using Discriminant Analysis of
      Principal Components (DAPC) revealed a broad admixture among P. homarus, however,
      Ashuwaymiyah stock appeared to be potentially under local adaptive pressures.
      Fine scale analysis using Netview R provided further support for the general
      admixture of P. homarus. CONCLUSIONS: Findings here suggested that stocks of P.
      homarus along the Omani coastline are admixed. Yet, fishery managers need to
      treat the lobster stock from Ashuwaymiyah with caution as it might be subject to
      local adaptive pressures. We emphasize further study with larger number of
      samples to confirm the genetic status of the Ashuwaymiyah stock. The approach
      utilised in this study has high transferability in conservation and management of
      other marine stocks with similar biological and ecological attributes.

PMID- 30231938
TI  - Iron deficiency during pregnancy is associated with a reduced risk of adverse
      birth outcomes in a malaria-endemic area in a longitudinal cohort study.
AB  - BACKGROUND: Low birth weight (LBW) and preterm birth (PTB) are major contributors
      to infant mortality and chronic childhood morbidity. Understanding factors that
      contribute to or protect against these adverse birth outcomes is an important
      global health priority. Anaemia and iron deficiency are common in malaria-endemic
      regions, but there are concerns regarding the value of iron supplementation among
      pregnant women in malaria-endemic areas due to reports that iron supplementation
      may increase the risk of malaria. There is a lack of evidence on the impact of
      iron deficiency on pregnancy outcomes in malaria-endemic regions. METHODS: We
      determined iron deficiency in a cohort of 279 pregnant women in a malaria-endemic
      area of Papua New Guinea. Associations with birth weight, LBW and PTB were
      estimated using linear and logistic regression. A causal model using sequential
      mediation analyses was constructed to assess the association between iron
      deficiency and LBW, either independently or mediated through malaria and/or
      anaemia. RESULTS: Iron deficiency in pregnant women was common (71% at enrolment)
      and associated with higher mean birth weights (230 g; 95% confidence interval, CI
      118, 514; p < 0.001), and reduced odds of LBW (adjusted odds ratio, aOR = 0.32;
      95% CI 0.16, 0.64; p = 0.001) and PTB (aOR = 0.57; 95% CI 0.30, 1.09; p = 0.089).
      Magnitudes of effect were greatest in primigravidae (birth weight 351 g; 95% CI
      188, 514; p < 0.001; LBW aOR 0.26; 95% CI 0.10, 0.66; p = 0.005; PTB aOR = 0.39,
      95% CI 0.16, 0.97; p = 0.042). Sequential mediation analyses indicated that the
      protective association of iron deficiency on LBW was mainly mediated through
      mechanisms independent of malaria or anaemia. CONCLUSIONS: Iron deficiency was
      associated with substantially reduced odds of LBW predominantly through malaria
      independent protective mechanisms, which has substantial implications for
      understanding risks for poor pregnancy outcomes and evaluating the benefit of
      iron supplementation in pregnancy. This study is the first longitudinal study to
      demonstrate a temporal relationship between antenatal iron deficiency and
      improved birth outcomes. These findings suggest that iron supplementation needs
      to be integrated with other strategies to prevent or treat infections and
      undernutrition in pregnancy to achieve substantial improvements in birth
      outcomes.

PMID- 30231937
TI  - The gut of the finch: uniqueness of the gut microbiome of the Galapagos vampire
      finch.
AB  - BACKGROUND: Darwin's finches are a clade of 19 species of passerine birds native
      to the Galapagos Islands, whose biogeography, specialized beak morphologies, and
      dietary choices-ranging from seeds to blood-make them a classic example of
      adaptive radiation. While these iconic birds have been intensely studied, the
      composition of their gut microbiome and the factors influencing it, including
      host species, diet, and biogeography, has not yet been explored. RESULTS: We
      characterized the microbial community associated with 12 species of Darwin's
      finches using high-throughput 16S rRNA sequencing of fecal samples from 114
      individuals across nine islands, including the unusual blood-feeding vampire
      finch (Geospiza septentrionalis) from Darwin and Wolf Islands. The phylum-level
      core gut microbiome for Darwin's finches included the Firmicutes,
      Gammaproteobacteria, and Actinobacteria, with members of the Bacteroidetes at
      conspicuously low abundance. The gut microbiome was surprisingly well conserved
      across the diversity of finch species, with one exception-the vampire finch-which
      harbored bacteria that were either absent or extremely rare in other finches,
      including Fusobacterium, Cetobacterium, Ureaplasma, Mucispirillum, Campylobacter,
      and various members of the Clostridia-bacteria known from the guts of carnivorous
      birds and reptiles. Complementary stable isotope analysis of feathers revealed
      exceptionally high delta15N isotope values in the vampire finch, resembling top
      marine predators. The Galapagos archipelago is also known for extreme wet and dry
      seasons, and we observed a significant seasonal shift in the gut microbial
      community of five additional finch species sampled during both seasons.
      CONCLUSIONS: This study demonstrates the overall conservatism of the finch gut
      microbiome over short (< 1 Ma) divergence timescales, except in the most extreme
      case of dietary specialization, and elevates the evolutionary importance of
      seasonal shifts in driving not only species adaptation, but also gut microbiome
      composition.

PMID- 30231939
TI  - A theory-based multi-component intervention to increase reactive balance
      measurement by physiotherapists in three rehabilitation hospitals: an
      uncontrolled single group study.
AB  - BACKGROUND: Most implementation interventions in rehabilitation, including
      physiotherapy, have used passive, non-theoretical approaches without demonstrated
      effectiveness. The goal of this study was to improve an important domain of
      physiotherapy practice - reactive balance measurement - with a targeted theory
      based multi-component intervention developed using the Theoretical Domains
      Framework. The primary objective was to determine documented reactive balance
      measure use in a 12-month baseline, during, and for three months post-
      intervention. METHODS: An uncontrolled before-and-after study was completed with
      physiotherapists at three urban adult rehabilitation hospitals in Ontario,
      Canada. The 12-month intervention included group meetings, local champions, and
      health record modifications for a validated reactive balance measure. The primary
      outcome was the proportion of records with a documented reactive balance measure
      when balance was assessed pre-, during- and post-intervention. Secondary outcomes
      were changes in use, knowledge, and confidence post-intervention, differences
      across sites, and intervention satisfaction. RESULTS: Reactive balance was not
      measured in any of 211 eligible pre-intervention records. Thirty-three
      physiotherapists enrolled and 28 completed the study. Reactive balance was
      measured in 31% of 300 eligible records during-intervention, and in 19% of 90
      eligible records post-intervention (p < 0.04). Knowledge and confidence
      significantly increased post-intervention (all p < 0.05). There were significant
      site differences in use during- and post-intervention (all p < 0.05). Most
      participants reported satisfaction with intervention content (71%) and delivery
      (68%). CONCLUSIONS: Reactive balance measurement was greater among participants
      during-intervention relative to the baseline, and use was partially sustained
      post-intervention. Continued study of intervention influences on clinical
      reasoning and exploration of site differences is warranted.

PMID- 30231940
TI  - JAG1 overexpression contributes to Notch1 signaling and the migration of HTLV-1
      transformed ATL cells.
AB  - BACKGROUND: HTLV-1 is a retrovirus that infects over 20 million people worldwide
      and is responsible for the hematopoietic malignancy adult T cell leukemia (ATL).
      We previously demonstrated that Notch is constitutively activated in ATL cells.
      Activating genetic mutations were found in Notch; however, Notch signaling was
      also activated in the absence of genetic mutations suggesting the existence of
      other mechanisms. METHODS: We analyzed the expression of Notch receptor ligands
      in HTLV-I-transformed cells, ATL patient-derived cell lines, and fresh uncultured
      ATL samples by RT-PCR, FACS, and immunohistochemistry. We then investigated viral
      and cellular molecular mechanisms regulating expression of JAG1. Finally, using
      shRNA knock-down and neutralizing antibodies, we investigated the function of
      JAG1 in ATL cells. RESULTS: Here, we report the overexpression of the Notch
      ligand, JAG1, in freshly uncultured ATL patient samples compared to normal PBMCs.
      We found that in ATL cells, JAG1 overexpression relies upon the viral protein Tax
      and cellular miR-124a, STAT3, and NFATc1. Interestingly, our data show that
      blockade of JAG1 signaling dampens Notch1 downstream signaling and limits cell
      migration of transformed ATL cells. CONCLUSIONS: Our results suggest that
      targeting JAG1 can block Notch1 activation in HTLV-I-transformed cells and
      represents a new target for immunotherapy in ATL patients.

PMID- 30231943
TI  - Cost-effectiveness of pre-operative Staphylococcus aureus screening and
      decolonization.
AB  - OBJECTIVE: We developed a decision analytic model to evaluate the impact of a
      preoperative Staphylococcus aureus decolonization bundle on surgical site
      infections (SSIs), health-care-associated costs (HCACs), and deaths due to SSI.
      METHODS: Our model population comprised US adults undergoing elective surgery. We
      evaluated 3 self-administered preoperative strategies: (1) the standard of care
      (SOC) consisting of 2 disinfectant soap showers; (2) the "test-and-treat"
      strategy consisting of the decolonization bundle including chlorhexidine
      gluconate (CHG) soap, CHG mouth rinse, and mupirocin nasal ointment for 5 days)
      if S. aureus was found at any of 4 screened sites (nasal, throat, axillary,
      perianal area), otherwise the SOC; and (3) the "treat-all" strategy consisting of
      the decolonization bundle for all patients, without S. aureus screening. Model
      parameters were derived primarily from a randomized controlled trial that
      measured the efficacy of the decolonization bundle for eradicating S. aureus.
      RESULTS: Under base-case assumptions, the treat-all strategy yielded the fewest
      SSIs and the lowest HCACs, followed by the test-and-treat strategy. In contrast,
      the SOC yielded the most SSIs and the highest HCACs. Consequently, relative to
      the SOC, the average savings per operation was $217 for the treat-all strategy
      and $123 for the test-and-treat strategy, and the average savings per per SSI
      prevented was $21,929 for the treat-all strategy and $15,166 for the test-and
      treat strategy. All strategies were sensitive to the probability of acquiring an
      SSI and the increased risk if SSI if the patient was colonized with SA.
      CONCLUSION: We predict that the treat-all strategy would be the most effective
      and cost-saving strategy for preventing SSIs. However, because this strategy
      might select more extensively for mupirocin-resistant S. aureus and cause more
      medication adverse effects than the test-and-treat approach or the SOC,
      additional studies are needed to define its comparative benefits and harms.

PMID- 30231941
TI  - Fertility in classical galactosaemia, a study of N-glycan, hormonal and
      inflammatory gene interactions.
AB  - BACKGROUND: Classical Galactosaemia (CG) (OMIM #230400) is a rare inborn error of
      galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate
      uridylyltransferase (GALT). Long-term complications persist in treated patients
      despite dietary galactose restriction with significant variations in outcomes
      suggesting epigenetic glycosylation influences. Primary Ovarian Insufficiency
      (POI) is a very significant complication affecting females with follicular
      depletion noted in early life. We studied specific glycan synthesis, leptin
      system and inflammatory gene expression in white blood cells as potential
      biomarkers of infertility in 54 adults with CG adults (27 females and 27 males)
      (age range 17-51 yr) on a galactose-restricted diet in a multi-site Irish and
      Dutch study. Gene expression profiles were tested for correlation with a serum
      Ultra-high Performance Liquid Chromatography (UPLC)-Immunoglobulin (IgG)-N-glycan
      galactose incorporation assay and endocrine measurements. RESULTS: Twenty five CG
      females (93%) had clinical and biochemical evidence of POI. As expected, the CG
      female patients, influenced by hormone replacement therapy, and the healthy
      controls of both genders showed a positive correlation between log leptin and BMI
      but this correlation was not apparent in CG males. The strongest correlations
      between serum leptin levels, hormones, G-ratio (galactose incorporation assay)
      and gene expression data were observed between leptin, its gene and G-Ratios data
      (rs = - 0.68) and (rs = - 0.94) respectively with lower circulating leptin in CG
      patients with reduced IgG galactosylation. In CG patients (males and females
      analysed as one group), the key glycan synthesis modifier genes MGAT3 and FUT8,
      which influence glycan chain bisecting and fucosylation and subsequent cell
      signalling and adhesion, were found to be significantly upregulated (p < 0.01 and
      p < 0.05) and also the glycan synthesis gene ALG9 (p < 0.01). Both leptin
      signalling genes LEP and LEPR were found to be upregulated (p < 0.01) as was the
      inflammatory genes ANXA1 and ICAM1 and the apoptosis gene SEPT4 (p < 0.01).
      CONCLUSIONS: These results validate our previous findings and provide novel
      experimental evidence for dysregulation of genes LEP, LEPR, ANXA1, ICAM1 and
      SEPT4 for CG patients and combined with our findings of abnormalities of IgG
      glycosylation, hormonal and leptin analyses elaborate on the systemic
      glycosylation and cell signalling abnormalities evident in CG which likely
      influence the pathophysiology of POI.

PMID- 30231944
TI  - New Image Texture Analysis, and Application to Polymer Membrane Surface
      Morphologies and Roughness.
AB  - A new method of image texture analysis is presented, based on the mean and
      standard deviation of gray levels within domains in an image. The calculations
      are performed recursively on domains of various sizes within the images. These
      gray level calculations are used as the input matrix for principal component
      analysis. The technique analyzes the entire image as a whole and is not for image
      segmentation. The analysis routine operates across all distances, frequencies and
      directions in the image, and is not computationally burdensome. The method was
      applied to scanning electron microscope images of reverse osmosis membranes on
      domains from 23 nm to 3 um. The texture analysis technique performed well in
      identifying the surface morphology and, once calibrated, in predicting the
      surface roughness as measured by atomic force microscopy.

PMID- 30231945
TI  - The importance of integrative approaches in nematode taxonomy: the validity of
      Parapharyngodon and Thelandros as distinct genera.
AB  - Despite the advances of molecular tools, new nematode species are still described
      mainly based on morphological characters. Parapharyngodon and Thelandros are two
      genera of oxyurids with unclear related taxonomic histories. Here we use
      morphological characters (linear measurements and categorical variables) and
      genetic information (18S rRNA, 28S rRNA and COI partial gene sequences) to
      confirm the relationships between representatives of these two genera and to
      determine whether they can be discriminated morphologically. Genetic results
      confirm the existence of two main clades, mostly congruent with Parapharyngodon
      and Thelandros genera but with several discordances. Thelandros is polyphyletic,
      with two of the species analysed (T. filiformis and T. tinerfensis) being part of
      the Thelandros clade, but with a third one (T. galloti) falling within the
      Parapharyngodon clade. Regarding the Parapharyngodon clade, P. cubensis, P.
      scleratus and Parapharyngodon sp. from Mexico form congruent lineages, while most
      P. echinatus samples cluster in another group, with one exception. Interestingly,
      P. micipsae samples are scattered across the Parapharyngodon clade, suggesting
      that they were misidentified or rather represent alternative morphotypes of other
      species. Morphological analysis identified the length of the tail, number of
      caudal papillae, position of the nerve ring, presence of caudal alae and length
      of the lateral alae as reliable characters to distinguish between Parapharyngodon
      and Thelandros genetic clades. Our study highlights the current taxonomic
      inconsistency in these groups, mainly derived from the exclusive use of
      morphological data. As such, we advocate for the routine implementation of
      molecular data in nematode taxonomic studies.

PMID- 30231946
TI  - The first record of Ligophorus Euzet & Suriano, 1977 (Monogenea: Dactylogyridae)
      on Crenimugil buchanani (Teleostei: Muglidae) from Thailand based on
      morphological and molecular analyses.
AB  - Ligophorus satunensis n. sp. was collected from the bluetail mullet, Crenimugil
      buchanani (Bleeker, 1853), caught off Satun, Thailand, representing the first
      report of the Ligophorus species in Thailand. The new species is most similar to
      Ligophorus fenestrum Soo & Lim, 2012 in its fenestrated dorsal hamuli, a ventral
      bar with a long, bifurcated anteromedian protuberance (AMP) without lateral
      pieces, and a non-sclerotized vagina. However, it differs from the latter in its
      dorsal hamuli (up to two layers of fenestrations of the dorsal hamuli in L.
      satunensis n. sp. vs six layers in L. fenestrum), ventral hamuli (nonfenestrated
      vs fenestrated), penis (turning a full circle before reaching the genital pore vs
      turning less than half a circle), and its accessory piece (non-grooved basally
      and grooved distally vs simply grooved along its entire length). A single
      specimen, very similar to L. satunensis n. sp., obtained from the same host fish,
      which can be differentiated from the latter by a considerably shorter AMP of the
      ventral bar and a smaller and slender dorsal hamuli, is tentatively designated
      here as Ligophorus sp. Moreover, the phylogenetic trees constructed from the
      concatenated sequences of partial large-subunit nuclear ribosomal DNA (28S) and
      nuclear ribosomal internal transcribed spacer 1 (ITS1) regions support that L.
      satunensis n. sp. is a new species closely related to L. fenestrum.

PMID- 30231947
TI  - The Mechanical Response of a Structural Epoxy Adhesive Reinforced with Carbon
      Black Nanoparticles.
AB  - The influence of the concentration of carbon black nanoparticles on the
      mechanical behavior of a structural adhesive was studied to evaluate and
      understand the stiffness, strength, and deformation behavior of a reinforced
      epoxy adhesive. Two carbon black nanoparticles with different dielectric
      properties and sizes (Monarch(r) 120 and Vulcan(r) XC72R) were studied. A bi
      component structural epoxy adhesive was selected. Specimens with different
      concentrations of carbon black were manufactured (0, 5, 10, and 20% on volume of
      resin) for each type of nanoparticle. The specimens were cured in a hydraulic hot
      plates press machine. The mechanical behavior of the adhesives was found not to
      vary significantly as a function of carbon black nanoparticles amount. A scanning
      electron microscopy analysis was performed to evaluate the fracture surface. The
      fracture surfaces of specimens were correlated with the mechanical response
      obtained through tensile tests.

PMID- 30231948
TI  - Epidemiology, detection, and management of tuberculosis among end-stage renal
      disease patients.
AB  - Tuberculosis (TB) remains an important problem among end-stage renal disease
      (ESRD) patients. We reviewed the epidemiology of TB and ESRD, investigations of
      TB exposures in US dialysis facilities, and published guidelines to inform
      screening and treatment practices among US ESRD patients. Compared to TB in the
      general population, ESRD patients have 6-25-fold higher TB incidence rates, and
      mortality during treatment is 2-3-fold higher. Most TB cases among ESRD patients
      (~90%) occur among non-US-born persons, and an analysis of genotyping data
      suggests that 80% of all cases result from latent TB infection (LTBI)
      reactivation. Published TB contact investigations in dialysis facilities have
      reported cases among ESRD patients and healthcare workers. However, transmission
      of TB is rare: there were no reports of secondary cases of TB because of exposure
      to an index-case patient and there were few TB infections, which was demonstrated
      by low occurrence of newly positive tuberculin skin tests (12%-16%) and
      conversions (8%-17%) among contacts. Targeted TB education, screening, and
      treatment for ESRD patients at highest risk for TB exposure (eg, non-US-born
      persons), using interferon-gamma release assays and short course LTBI regimens
      (ie, isoniazid-rifapentine weekly for 12 weeks or rifampin daily for 4 months)
      may be an effective overall strategy for reducing TB burden in ESRD patients.

PMID- 30231942
TI  - Transcriptomic but not genomic variability confers phenotype of breast cancer
      stem cells.
AB  - BACKGROUND: Breast cancer stem cells (BCSCs) are considered responsible for
      cancer relapse and drug resistance. Understanding the identity of BCSCs may open
      new avenues in breast cancer therapy. Although several discoveries have been made
      on BCSC characterization, the factors critical to the origination of BCSCs are
      largely unclear. This study aimed to determine whether genomic mutations
      contribute to the acquisition of cancer stem-like phenotype and to investigate
      the genetic and transcriptional features of BCSCs. METHODS: We detected potential
      BCSC phenotype-associated mutation hotspot regions by using whole-genome
      sequencing on parental cancer cells and derived serial-generation spheres in
      increasing order of BCSC frequency, and then performed target deep DNA sequencing
      at bulk-cell and single-cell levels. To identify the transcriptional program
      associated with BCSCs, bulk-cell and single-cell RNA sequencing was performed.
      RESULTS: By using whole-genome sequencing of bulk cells, potential BCSC phenotype
      associated mutation hotspot regions were detected. Validation by target deep DNA
      sequencing, at both bulk-cell and single-cell levels, revealed no genetic changes
      specifically associated with BCSC phenotype. Moreover, single-cell RNA sequencing
      showed profound transcriptomic variability in cancer cells at the single-cell
      level that predicted BCSC features. Notably, this transcriptomic variability was
      enriched during the transcription of 74 genes, revealed as BCSC markers. Breast
      cancer patients with a high risk of relapse exhibited higher expression levels of
      these BCSC markers than those with a low risk of relapse, thereby highlighting
      the clinical significance of predicting breast cancer prognosis with these BCSC
      markers. CONCLUSIONS: Transcriptomic variability, not genetic mutations,
      distinguishes BCSCs from non-BCSCs. The identified 74 BCSC markers have the
      potential of becoming novel targets for breast cancer therapy.

PMID- 30231949
TI  - Effect of copper-impregnated linens on multidrug-resistant organism acquisition
      and Clostridium difficile infection at a long-term acute-care hospital.
AB  - Copper-impregnated surfaces and linens have been shown to reduce infections and
      multidrug-resistant organism (MDRO) acquisition in healthcare settings. However,
      retrospective analyses of copper linen deployment at a 40-bed long-term acute
      care hospital demonstrated no significant reduction in incidences of healthcare
      facility-onset Clostridium difficile infection or MDRO acquisition.

PMID- 30231951
TI  - Distribution of the newly invasive New Guinea flatworm Platydemus manokwari
      (Platyhelminthes: Geoplanidae) in Thailand and its potential role as a paratenic
      host carrying Angiostrongylus malaysiensis larvae.
AB  - Invasive species constitute one of the most serious threats to biodiversity and
      ecosystems, and they potentially cause economic problems and impact human health.
      The globally invasive New Guinea flatworm, Platydemus manokwari (Platyhelminthes:
      Geoplanidae), has been identified as a threat to terrestrial biodiversity,
      particularly soil-dwelling native species (e.g. molluscs, annelids and other land
      planarians), and is listed among 100 of the world's worst invasive alien species.
      We report here, for the first time, P. manokwari occurrences in many locations
      throughout Thailand, using voluntary digital public participation from the social
      network portals associated with the Thailand Biodiversity Conservation Group and
      collections of living flatworm specimens. Mitochondrial cytochrome c oxidase
      subunit I (COI) sequences confirmed that all collected flatworms were P.
      manokwari and placed them in the "world haplotype" clade alongside other
      previously reported specimens from France, Florida (USA), Puerto Rico, Singapore,
      French Polynesia, New Caledonia, and the Solomon Islands. In addition, infective
      stage larvae (L3) of the nematode Angiostrongylus malaysiensis were found in the
      flatworm specimens, with a 12.4% infection rate (15/121 specimens examined).
      Platydemus manokwari occurrence in Thailand and its capacity to carry L3 of
      Angiostrongylus should be of concern to biodiversity conservation and human
      health practitioners, because this invasive flatworm species may be involved in
      the life cycle of angiostrongylid worms in Thailand.

PMID- 30231950
TI  - An electronic antimicrobial stewardship intervention reduces inappropriate
      parenteral antibiotic therapy.

PMID- 30231953
TI  - Phylogenetic relationships of the family Gryporhynchidae (Cestoda:
      Cyclophyllidea) inferred through SSU and LSU rDNA sequences.
AB  - Tapeworms of the family Gryporhynchidae are endoparasites of fish-eating birds
      distributed worldwide. Currently the family contains 16 genera classified on the
      basis of the morphology of the rostellar apparatus, rostellar hooks and strobilar
      anatomy. However, the phylogenetic relationships among the genera are still
      unknown. In this study, sequences of the near complete 18S (SSU) and 28S (LSU)
      from rDNA of 13 species of gryporhynchids (adult specimens) representing eight
      genera (Cyclustera, Dendrouterina, Glossocercus, Gryporhynchidae gen. sp.,
      Neovalipora, Paradilepis, Parvitaenia, Valipora) and one species of metacestode
      from fish (Neovalipora) were generated. Additionally, sequences of metacestodes
      of the genera Amirthalingamia, Neogryporhynchus, Paradilepis, Parvitaenia and
      Valipora from Africa recently added to the GenBank database were analysed.
      Phylogenetic relationships were inferred using maximum-likelihood (ML) and
      Bayesian inference of each (SSU and LSU) dataset. The phylogenetic analyses
      indicated that the family Gryporhynchidae is a well-supported monophyletic group
      within the Cyclophyllidea. The trees inferred with SSU and LSU datasets had
      similar topologies and suggested that the genera Glossocercus (two species
      sequenced) and Paradilepis (four spp.) are monophyletic. In contrast,
      Dendrouterina, Parvitaenia and Valipora are paraphyletic, suggesting that the
      species composition of these genera should be critically reviewed. Interestingly,
      species of the genera that use the same groups of definitive hosts such as herons
      (Ardeidae), cormorants (Phalacrocoracidae) and ibis (Threskiornithidae) are
      together in the phylogenetic tree, even though they differ markedly from each
      other in some morphological characters, especially shape and size of rostellar
      hooks.

PMID- 30231952
TI  - Spanish and Portuguese Gilding Threads: Characterization Using Microscopic
      Techniques.
AB  - Gilding threads collected from Spanish and Portuguese palaces and from the
      embroideries and adornments of sculptures of the Virgin and Christ that form part
      of Sevillian Holy Week were analyzed and compared (20 artifacts were evaluated).
      The study covered a broad time period with examples from the 13th to 14th
      centuries, 18th to 20th centuries, and also including modern embroideries. A
      combination of scanning electron microscopy and energy-dispersive X-ray
      spectroscopy was used. The knowledge of the layered structures of the threads has
      provided very valuable information regarding the manufacturing techniques. The
      different metal threads found in the embroidery studied consisted of gold,
      silver, copper, and alloys of these metals and aluminium. The fabrication
      procedures often differed in the different workshops and changed with time. In
      the modern embroideries, a decrease of precious metal concentration was detected.
      The threads were wound around a core of silk threads.

PMID- 30231954
TI  - CO 2 Supercritical Extraction of Essential Oil of Jordanian Rosemary.
AB  - Background: Experimental investigation of supercritical fluid extraction (SFE) of
      active ingredients from rosemary herb has been performed. Carbon dioxide (CO2)
      was used as a solvent with ethanol as a trapping agent. This work showed that the
      SFE can be an exceptional alternative to the use of chemical solvents. Objective:
      The effect of temperature and pressure on the extraction process was investigated
      to increase the yield of the extracted essential components. Methods: The types
      of extracted compounds from rosemary were specified and analyzed using GC-MS.
      Results: The results indicated that several essential active ingredient compounds
      were extracted. Furthermore, the pressure affects the extraction, as the
      composition of some compounds increases with a pressure increase. Conclusions:
      SFE can be used to extract valuable active ingredients from rosemary. Two process
      parameters were investigated, namely, pressure and temperature, which indicate
      that SFE is a selective process for the production of certain constituents.
      Highlights: Some of the main components of the essential oil of Jordanian
      rosemary obtained in this study have important applications in pharmaceutical and
      cosmetic products. For instance, alpha-pinene is one of the main raw compounds
      used in the perfume industry.

PMID- 30231955
TI  - Application of Capillary Zone Electrophoresis Coupled with a Diode Array Detector
      (CZE-DAD) to Simultaneous Analysis of Ibuprofen and Phenylephrine.
AB  - Background: A validated method based on capillary zone electrophoresis coupled
      with a diode array detector (CZE-DAD) was investigated for analyzing binary
      mixture of ibuprofen (IBU) and phenylephrine (PHE) in their bulk and combined
      dosage form. Objective: This binary mixture is a challenging one as IBU is acidic
      and PHE is alkaline, which may affect their simultaneous analysis using CZE. The
      literature lacks any CZE report for IBU and PHE simultaneous analysis. Methods:
      Fused silica capillary (85 cm * 75 MUm id) was used, and the electrolyte was a 50
      mM borate buffer adjusted to pH 11 with 0.5 M NaOH. Results: The concentration
      ranges were 5-200 and 5-100 MUg/mL for IBU and PHE, respectively, using CZE. High
      efficiency was achieved (N > 92990). Reasonable migration time (tm) was attained
      (tm< 8.5 min). Conclusions: Although the results obtained by the proposed CZE
      method and reported HPLC method were statistically comparable, the proposed
      method showed lower linearity ranges, higher efficiency, and a more reasonable
      run time. Highlights: CZE-DAD was used for the analysis of IBU and PHE in bulk
      and tablets, as no report was found for their determination using CZE. Binary
      mixture is challenging due to differences in chemical and physical properties. A
      detailed discussion of electrophoretic parameters optimization is included.
      Confirmation of peak purity was attained using DAD.

PMID- 30231956
TI  - A definition of the Mycobacterium avium complex for taxonomical and clinical
      purposes, a review.
AB  - Nontuberculous mycobacteria, particularly the Mycobacterium avium complex (MAC)
      bacteria, are increasingly recognized as opportunistic pathogens of humans. As a
      result, studies on antibiotic treatment and taxonomy of the MAC are intensifying,
      but an updated definition of what constitutes the MAC, either for taxonomical
      studies or for clinical purposes, is lacking. On the basis of literature review
      and phylogenetic analyses, we propose to define the MAC as a grouping of slow
      growing mycobacteria that show corresponding values in at least two of the
      following targets against either M. avium ATCC 25291T or Mycobacterium
      intracellulare ATCC 13950T: >99.4 % sequence identity for the full 16S rRNA gene,
      >98.7 % for the partial (5') 16S rRNA gene, >97.3 % for hsp65 and >94.4 % for
      rpoB region V. A >97.5 % value in concatenated analyses of >2500 bp that includes
      16S rRNA, hsp65 and rpoB gene sequence data or >=85 % average nucleotide identity
      to M. avium ATCC 25291T or M. intracellulare ATCC 13950T on basis of whole genome
      sequencing data is recommended. This molecular definition is based on the
      distances observed between the classical members of the MAC, M. avium and M.
      intracellulare. Applying this definition, the complex currently consists of 12
      validly published species: Mycobacterium avium, Mycobacterium intracellulare,
      Mycobacterium chimaera, Mycobacterium colombiense, Mycobacterium arosiense,
      Mycobacterium vulneris, Mycobacterium bouchedurhonense, Mycobacterium timonense,
      Mycobacterium marseillense, Mycobacterium yongonense, Mycobacterium
      paraintracellulare and Mycobacterium lepraemurium.

PMID- 30231957
TI  - Reichenbachiella versicolor sp. nov., isolated from red alga.
AB  - A Gram-stain-negative, strictly aerobic, non-flagellated, rod-shaped bacterial
      strain, designated DC003T, was isolated from the alga Gracilariablodgettii of the
      phylum Rhodophyta collected from the coast of Lingshui county, Hainan, China. The
      strain grew optimally at 28  degrees C, pH 7.0-7.5 and in the presence of 2.0-3.0
      % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed
      strain DC003T to be within the genus Reichenbachiella, and most closely related
      to Reichenbachiella agariperforans JCM11238 (94.5 %), followed by
      Reichenbachiella faecimaris JCM 16588T (94.2 %). The major respiratory quinone
      was menaquinone 7 and the major fatty acids were iso-C15 : 0 and summed feature 3
      (C16 : 1omega7c and/or iso-C15 : 0 2-OH). The polar lipids consisted of
      phosphatidylethanolamine, two unidentified aminophospholipids, three unidentified
      phospholipids and 10 unidentified lipids. The G+C content of the genomic DNA was
      37.1 mol%. On the basis of the phenotypic, genotypic and phylogenetic analysis,
      strain DC003T is considered to represent a novel species of the genus
      Reichenbachiella, for which the name Reichenbachiellaversicolor sp. nov. is
      proposed. The type strain is DC003T (=KCTC 42867T=MCCC 1H00130T).

PMID- 30231958
TI  - Marinobacter bohaiensis sp. nov., a moderate halophile isolated from benthic
      sediment of the Bohai Sea.
AB  - A Gram-stain-negative, motile, aerobic and rod-shaped bacterial strain,
      designated T17T, was isolated from benthic sediment sampled at Jiaozhou Bay,
      Bohai Sea, China, and its taxonomic position was investigated. The 16S rRNA gene
      sequence of strain T17T exhibited the highest similarity values to those of the
      type strain Marinobacter lacisalsi FP2.5 (96.2 %) and Marinobacter koreensis DD
      M3T (96.2 %). Strain T17T grew optimally at 35  degrees C, pH 7.0-8.0 and in the
      presence of 6.0-10.0 % (w/v) NaCl. The predominant ubiquinone in strain T17T was
      identified as Q-9. The major fatty acids of strain T17T were C12 : 0, C16 : 0 and
      C16 : 0 10-CH3. The major polar lipids of strain T17T were
      phosphatidylethanolamine, phosphatidylglycerol, diphosphatidglycerol, an
      unidentified aminolipid and an unidentified phospholipid. The DNA G+C content of
      strain T17T was 63.0 mol%. The draft genome sequence of strain T17T includes 4
      755 891 bp in total (N50=2 856 325 bp) with a medium read coverage of 100.0x and
      11 scaffolds. In silico DNA-DNA hybridization with the three type strains showed
      20.3, 19.7 and 19.9 % relatedness to Marinobacter santoriniensis NKSG1T,
      Marinobacter segnicrescens SS11B1-4T and Marinobacter daqiaonensis CGMCC 1.9167T,
      respectively. On the basis of the phenotypic, phylogenetic, genomic and
      chemotaxonomic properties, strain T17T is considered to represent a novel species
      within the genus Marinobacter, for which the name Marinobacterbohaiensis sp. nov.
      is proposed. The type strain is T17T (=KCTC 52710T=MCCC 1K03282T).

PMID- 30231959
TI  - Lentzea terrae sp. nov., isolated from soil and an emended description of Lentzea
      soli.
AB  - A novel actinobacterium, designated strain NEAU-LZS 42T, was isolated from soil
      collected from Mount Song, Henan Province, China, and characterized using a
      polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that the organism should be assigned to the genus Lentzea and had the
      closest relationship with Lentzea soli NEAU-LZC 7T (99.1 % similarity) and
      Lentzea cavernae SYSU K10001T (98.2 %). The major menaquinones were identified as
      MK-9(H4) and MK-9(H2). The phospholipid profile was found to contain
      diphosphatidylglycerol, phosphatidylethanolamine, hydroxy
      phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside,
      glycophospholipid and three unidentified lipids. The major fatty acids were iso
      C16 : 0, C16 : 1omega7c and C16 : 0. DNA-DNA hybridization results and some
      phenotypic characteristics indicated that strain NEAU-LZS 42T could be clearly
      differentiated from L. soli NEAU-LZC 7T and L. cavernae SYSU K10001T. Therefore,
      it is concluded that strain NEAU-LZS 42T represents a novel species of the genus
      Lentzea, for which the name Lentzea terrae sp. nov. is proposed. The type stain
      is NEAU-LZS 42T (=CGMCC 4.7428T=DSM 105696T).

PMID- 30231960
TI  - Real-time Microwave Exposure Induces Calcium Efflux in Primary Hippocampal
      Neurons and Primary Cardiomyocytes.
AB  - OBJECTIVE: To detect the effects of microwave on calcium levels in primary
      hippocampal neurons and primary cardiomyocytes by the real-time microwave
      exposure combined with laser scanning confocal microscopy. METHODS: The primary
      hippocampal neurons and primary cardiomyocytes were cultured and labeled with
      probes, including Fluo-4 AM, Mag-Fluo-AM, and Rhod-2, to reflect the levels of
      whole calcium [Ca2+], endoplasmic reticulum calcium [Ca2+]ER, and mitochondrial
      calcium [Ca2+]MIT, respectively. Then, the cells were exposed to a pulsed
      microwave of 2.856 GHz with specific absorption rate (SAR) values of 0, 4, and 40
      W/kg for 6 min to observe the changes in calcium levels. RESULTS: The results
      showed that the 4 and 40 W/kg microwave radiation caused a significant decrease
      in the levels of [Ca2+], [Ca2+]ER, and [Ca2+]MIT in primary hippocampal neurons.
      In the primary cardiomyocytes, only the 40 W/kg microwave radiation caused the
      decrease in the levels of [Ca2+], [Ca2+]ER, and [Ca2+]MIT. Primary hippocampal
      neurons were more sensitive to microwave exposure than primary cardiomyocytes.
      The mitochondria were more sensitive to microwave exposure than the endoplasmic
      reticulum. CONCLUSION: The calcium efflux was occurred during microwave exposure
      in primary hippocampal neurons and primary cardiomyocytes. Additionally, neurons
      and mitochondria were sensitive cells and organelle respectively.

PMID- 30231961
TI  - Evaluation of the New Automatic Mycob.T Stainer and Scanner for Detecting Acid
      fast Bacilli in China.
AB  - OBJECTIVE: To validate the performance of Mycob. T Stainer and Scanner (MTSS) for
      detecting acid-fast bacilli (AFB). METHODS: A total of 3,816 sputum samples from
      1,515 tuberculosis (TB) suspects were tested at the Anhui Provincial Chest
      Hospital and the Linyi People's Hospital from April-August, 2016. Each specimen
      was placed on two smear slides. One slide was stained by the ziehl-neelsen (ZN)
      method to be read by conventional microscopy (CM). The other slide was stained
      and scanned by MTSS. All specimens were decontaminated with 4% NaOH, and then
      inoculated into solid culture. The performance of MTSS was assessed. RESULTS:
      MTSS produced higher average positivity rate (27.96%) as compared with the CM
      (26.83%). The overall sensitivity and specificity of MTSS were 78.9% and 93.9%,
      respectively. The sensitivity and specificity of CM was 77.4% and 95.0%,
      respectively. CONCLUSION: MTSS exhibited a favorable performance in the detection
      of AFB. It may be an alternative to CM for screening TB.

PMID- 30231962
TI  - Genetic and Antibiotic Resistance Characteristics of Campylobacter jejuni
      Isolated from Diarrheal Patients, Poultry and Cattle in Shenzhen.
AB  - OBJECTIVE: To investigate genetic and antibiotic resistance characteristics of
      Campylobacter jejuni (C. jejuni) isolated from Shenzhen. METHODS: Multilocs
      sequence typing and agar dilution methods were used to define the genotype and
      antibiotic resistance of C. jejuni, respectively. RESULTS: In total, 126 C.
      jejuni strains were isolated. The prevalence of C. jejuni was 5.3% in diarrheal
      patients. The prevalence in poultry meat (36.5%) was higher than that in cattle
      meat (1.1%). However, the prevalence in poultry cloacal swabs (27.0%) was lower
      than that in cattle stool (57.3%). Sixty-two sequence types were obtained, among
      which 27 of the STs and 10 alleles were previously unreported. The most
      frequently observed clonal complexes were ST 21 (11.9%), ST-22 (10.3%), and ST
      403 (7.1%). ST-21, ST-45, ST-354, ST-403, and ST-443 complexes overlapped between
      isolates from patients and cattle, whereas ST-45 and ST-574 complexes overlapped
      between isolates from patients and poultry. All C. jejuni were resistant to at
      least one antibiotic. The highest resistance rate was toward ciprofloxacin
      (89.7%), followed by tetracycline (74.6%), and nalidixic acid (69.0%).
      CONCLUSION: This is the first report of the genotypes and antibiotic resistance
      of C. jejuni in Shenzhen. Overlapping clonal complexes were found between
      isolates from patients and cattle, and between patients and poultry.

PMID- 30231963
TI  - Specific CYP450 Genotypes in the Chinese Population Affect Sorafenib Toxicity in
      HBV/HCV-associated Hepatocellular Carcinoma Patients.
AB  - OBJECTIVE: The purpose of this study was to screen for frequencies of different
      CYP450 genotypes in the Chinese population and explore the relationship between
      sorafenib toxicity and CYP450 polymorphism. METHODS: A total of 600 peripheral
      blood samples were obtained from two groups for this study. The first group of
      300 samples were from Chinese patients with HBV/HCV-associated HCC, while the
      remaining 300 samples were from a healthy population of recruited subjects.
      Allele-specific PCR and long-fragment gene sequencing was used to identify the
      frequencies of CYP450 polymorphism. Aflatoxin-induced HCC rat models expressing
      CYP3A4*1, CYP3A5*3, CYP2C19*2, and CYP2D6*10 were established and treated with
      sorafenib at certain time points. Hepatic and renal function, along with plasma
      concentration of sorafenib, were monitored regularly. RESULTS: The most common
      forms of CYP mutations in the Chinese population were identified. The levels of
      sorafenib plasma concentration, as well as damage to hepatic and renal function
      in aflatoxin-induced HCC rat models varied significantly across the different CYP
      genotypes. CONCLUSION: The mutational frequencies of CYP3A5, CYP3A4, CYP2C19, and
      CYP2D6 genotypes varied among different ethnic groups and populations.
      Individuals with CYP3A5*3 demonstrated minimal sorafenib metabolism, which led to
      severe hepatic and renal damage. Inter-individual variability in sorafenib
      toxicity may be interpreted by CYP450 genetic polymorphisms, suggesting that
      identification of CYP polymorphism within a certain population should be
      considered in sorafenib therapy.

PMID- 30231964
TI  - Role of Ultrasound Lung Comets in the Diagnosis of Acute Heart Failure in
      Emergency Department: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: A new technique of transthoracic lung ultrasonography (TLS) has
      emerged and demonstrated promising results in acute heart failure diagnosis at an
      early stage. However, the diagnostic value of ultrasound lung comets (ULCs) for
      acute heart failure (AHF) performed in busy emergency department (ED) is
      uncertain. The present meta-analysis aimed to assess the diagnostic efficiency of
      ULCs in AHF. METHODS: We conducted a search on online journal databases to
      collect the data on TLS performed for diagnosing AHF published up to the end of
      July 2017. The sensitivity, specificity, positive likelihood ratio (PLR),
      negative likelihood ratio (NLR), and summary receiver operating characteristic
      (SROC) curve were calculated. The post-test probability of AHF was calculated by
      using Bayes analysis. RESULTS: We enrolled a total of 15 studies involving 3,309
      patients. The value of sensitivity, specificity, PLR, NLR, DOR, area under the
      SROC curve, and Q* index was 85%, 91%, 8.94, 0.14, 67.24, 0.9587, and 0.9026,
      respectively. We detected significant heterogeneity among included studies, and
      therefore, all these results were analyzed under the random-effect model. We also
      explored possible sources of heterogeneity among the studies by using meta
      regression analysis. Results suggest that the time interval between patient's
      admission to bedside TLS examination was closely related to TLS accuracy.
      CONCLUSION: This meta-analysis demonstrated that detecting ULCs is a convenient
      bedside tool and has high accuracy for early AHF diagnosis in ED. TLS could be
      recommended to be applied for early diagnosis of AHF in ED.

PMID- 30231965
TI  - LncRNA LUCAT1 Activation Mediated by the Down-regulation of DNMT1 Is Involved in
      Cell Apoptosis Induced by PM2.5.

PMID- 30231966
TI  - C57BL/6 and DBA/1 Mice Differ in Their Response to Supplementation with 1,25D and
      Paricalcitol.

PMID- 30231967
TI  - Association of PPARgamma and AGTR1 Polymorphisms with Hypertriglyceridemia in
      Chinese Population.

PMID- 30231968
TI  - Cost-effectiveness Analysis of Two Therapeutic Regimens for Newly Diagnosed Smear
      negative Pulmonary Tuberculosis.

PMID- 30231969
TI  - Effects of Omethoate on Liver Insulin Signaling in Mice.

PMID- 30231970
TI  - Mutagenicity and Genotoxicity of Organic Extracts from Finished Water with
      Different Treatment Process.

PMID- 30231974
TI  - Immunity in the Very Young: Challenges and Opportunities.
AB  - Immunity in early life encompasses the delicate interphase at the maternal-fetal
      stage, as well as rapid development and adaptation that occur as the newborn
      transitions from the protected maternal environment to functioning in the outside
      world. Understanding the forces that shape immunity in the very young and that
      lay the groundwork for an effective adult immune system holds both questions and
      promise.

PMID- 30231972
TI  - Factors Associated With Adherence to Statin Medications of Patients Enrolled in a
      Self-insured University Health Plan.
AB  - PURPOSE: The purpose of this study was to examine the association of patient and
      prescription factors with statin adherence of patients enrolled a self-insured
      university health plan. METHODS: We conducted a retrospective, longitudinal
      analysis of pharmacy claims data from a self-insured university for those
      enrollees prescribed a statin during a 38-month period (2009-2012). Adherence was
      calculated as the portion of days covered and was defined as portion of days
      covered >=80%. To be included in the study, patients had to have >=2 statin
      claims and be continuously enrolled in the plan. A logistic regression model was
      constructed to identify longitudinal predictors of adherence. In addition, a Cox
      proportional hazards model was run to examine predictors of adherence during
      1year of statin therapy. FINDINGS: There were 222 patients in the study. These
      222 patients generated a total of 3,349 statin claims. With a mean (SD)
      observation period of 970 (346.5) days, those patients taking statin medications
      had a mean adherence rate of 54.5%. Adherent and nonadherent patients were
      similar regardless of statin switching and inferred household income. However,
      those patients with greater adherence levels were older, more likely to be male,
      had previous statin exposure, paid higher mean copayments, and were more likely
      to use mail order as their delivery channel. In logistic regression, older age
      (odds ratio [OR] = 1.07, P = 0.001), male sex (OR = 1.79, P = 0.047), and the use
      of mail order (OR = 3.07, P = 0.002) were significantly associated with
      adherence. Of the original 222 patients, 200 patients completed 1 full year of
      therapy. In a subsequent Cox proportional hazards analysis, the retail delivery
      channel (hazard ratio = 1.904, P = 0.025) was associated with higher risk for
      nonadherence during a 1-year period. IMPLICATIONS: Despite the benefits
      associated with statin medications, adherence remains a challenge for certain
      groups of patients, including patients who are female, younger patients, and
      patients who use retail pharmacies (vs mail order) when filling their
      prescriptions. Health care professionals and employers, especially those
      employers who are self-insured, would be well served in developing adherence
      interventions aimed at these specific populations.

PMID- 30231973
TI  - Adolescent de novo hydroceles - should they be dealt with by inguinal or scrotal
      approach?
AB  - AIM: The objective of this study was to investigate the optimal approach for the
      treatment of hydroceles in adolescents. MATERIALS AND METHODS: A retrospective
      chart review of all adolescents (10-16 years old) diagnosed with a de-novo
      hydrocele in 2 tertiary care institutions over a 10 year period (2007-2016) was
      performed comparing the inguinal and trans-scrotal (Jaboulay) approaches.
      RESULTS: Fifty-three boys with a mean age of 13.4 years (range 10-16 years) were
      diagnosed with hydrocele. The inguinal approach was used in 31 (59%) patients for
      treatment of their hydrocele. In 19 (61%) of these cases a patent processus
      vaginalis (PPV) ligation was performed. In the other 12 (39%) patients the PPV
      was closed or not found and a further repair of the hydrocele through the same
      inguinal incision was performed. A transcrotal Jaboulay procedure was performed
      in 22 (41%) of the patients. There was no difference in the complications rate
      between inguinal and trans-scrotal approaches (p = 0.71). Age of presentation
      less than 12 years was associated with the presence of a PPV (p < 0.05).
      CONCLUSIONS: A trans-scrotal approach should be considered as first-line in
      adolescents when the history is not suggestive of a communicating hydrocele.
      Children less than 12 years of age are more likely to have a PPV and an inguinal
      approach may be more appropriate. TYPE OF STUDY: Retrospective comparative study
      LEVEL OF EVIDENCE: Level II.

PMID- 30231971
TI  - YAP drives cutaneous squamous cell carcinoma formation and progression.
AB  - Squamous cell carcinoma (SCC) can progress to malignant metastatic cancer,
      including an aggressive subtype known as spindle cell carcinoma (spSCC). spSCC
      formation involves epithelial-to-mesenchymal transition (EMT), yet the molecular
      basis of this event remains unknown. The transcriptional co-activator YAP
      undergoes recurrent amplification in human SCC and overexpression of YAP drives
      SCC formation in mice. Here, we show that human spSCC tumours also feature strong
      nuclear localisation of YAP and overexpression of activated YAP (NLS-YAP-5SA)
      with Keratin-5 (K5-CreERt) is sufficient to induce rapid formation of both SCC
      and spSCC in mice. spSCC tumours arise at sites of epithelial scratch wounding,
      where tumour-initiating epithelial cells undergo EMT to generate spSCC.
      Expression of the EMT transcription factor ZEB1 arises upon wounding and is a
      defining characteristic of spSCC in mice and humans. Thus, the wound healing
      response synergises with YAP to drive metaplastic transformation of SCC to spSCC.

PMID- 30231975
TI  - Ion Man: GSDMD Punches Pores to Knock Out cGAS.
AB  - The pore-forming protein GSDMD promotes cytokine release and induces pyroptotic
      cell death. In this issue of Immunity, Banerjee et al. (2018) document how GSDMD
      triggers potassium efflux to inhibit cGAS-STING and prevent damaging interferon
      production after bacterial infection.

PMID- 30231976
TI  - Two-Factor Authentication for Type 2 Immunity.
AB  - The initiation of type 2 responses is tightly regulated. In this issue of
      Immunity, Sokol et al. (2018) demonstrate that CCL8 is a critical signal that
      licenses dendritic cells to enter the lymph node parenchyma and induce Th2
      differentiation after allergen exposure.

PMID- 30231977
TI  - Fungi Enter the Stage of Colon Carcinogenesis.
AB  - The significant contribution of intestinal bacteria for the pathogenesis of
      colorectal cancer is widely accepted by now. In this issue of Immunity, two
      articles by Malik et al. (2018) and Wang et al. (2018) highlight the role of
      commensal fungi, which so far have been underestimated.

PMID- 30231978
TI  - Gone with the Antibody.
AB  - Bacterial metabolites can reach distant organs, and in this issue of Immunity,
      Uchimura et al. (2018) show a fast systemic distribution of microbiota
      metabolites. This distribution is controlled by antibodies that accelerate
      bacterial transit through the small intestine, resulting in reduced local and
      systemic metabolite penetration and attenuation of immune responses.

PMID- 30231979
TI  - Identifying the Patterns of Pattern Recognition Receptors.
AB  - Intestinal homeostasis requires microbial recognition that results in appropriate
      responses to commensals and pathogens. In this issue of Immunity, Price et al.
      (2018) map the in vivo expression of five toll-like receptors (TLR) in intestinal
      epithelia, revealing distinct spatio-temporal expression patterns that shape
      responses to TLR ligands.

PMID- 30231980
TI  - Viral Anti-CRISPR Tactics: No Success without Sacrifice.
AB  - Co-evolution with their bacterial hosts has led to viral countermeasures against
      CRISPR-mediated immunity. In a recent issue of Cell, Landsberger et al. (2018)
      and Borges et al. (2018) report that cooperation among bacteriophages and
      multiple infection events are necessary to overcome CRISPR immune responses.

PMID- 30231981
TI  - Tissue Crosstalk in T1D: Is Insulin Special?
AB  - In a recent issue of Nature,Wan et al. (2018) show that glucose-stimulated beta
      cells secrete insulin B chain peptides relevant to autoimmunity in type 1
      diabetes. Peptides such as insulin B:12-20 are released into circulation, where
      they can be directly and broadly presented by antigen-presenting cells throughout
      the lymphatic system.

PMID- 30231984
TI  - The Adaptor Protein CARD9 Protects against Colon Cancer by Restricting Mycobiota
      Mediated Expansion of Myeloid-Derived Suppressor Cells.
AB  - The adaptor protein CARD9 links detection of fungi by surface receptors to the
      activation of the NF-kappaB pathway. Mice deficient in CARD9 exhibit dysbiosis
      and are more susceptible to colitis. Here we examined the impact of Card9
      deficiency in the development of colitis-associated colon cancer (CAC). Treatment
      of Card9-/- mice with AOM-DSS resulted in increased tumor loads as compared to WT
      mice and in the accumulation of myeloid-derived suppressor cells (MDSCs) in tumor
      tissue. The impaired fungicidal functions of Card9-/- macrophages led to
      increased fungal loads and variation in the overall composition of the intestinal
      mycobiota, with a notable increase in C. tropicalis. Bone marrow cells incubated
      with C. tropicalis exhibited MDSC features and suppressive functions. Fluconazole
      treatment suppressed CAC in Card9-/- mice and was associated with decreased MDSC
      accumulation. The frequency of MDSCs in tumor tissues of colon cancer patients
      correlated positively with fungal burden, pointing to the relevance of this
      regulatory axis in human disease.

PMID- 30231986
TI  - Michel Jouvet: a personal and philosophical tribute.
AB  - Major events in the long history of paradoxical sleep research, such as the
      crisis of the monoaminergic theory of sleep, as well as subsequent discoveries
      and theoretical functional hypotheses, are presented from an epistemological and
      a more general philosophical point of view.

PMID- 30231985
TI  - SYK-CARD9 Signaling Axis Promotes Gut Fungi-Mediated Inflammasome Activation to
      Restrict Colitis and Colon Cancer.
AB  - Fungi represent a significant proportion of the gut microbiota. Aberrant immune
      responses to fungi are frequently observed in inflammatory bowel diseases (IBD)
      and colorectal cancer (CRC), and mutations in the fungal-sensing pathways are
      associated with the pathogenesis of IBD. Fungal recognition receptors trigger
      downstream signaling via the common adaptor protein CARD9 and the kinase SYK.
      Here we found that commensal gut fungi promoted inflammasome activation during
      AOM-DSS-induced colitis. Myeloid cell-specific deletion of Card9 or Syk reduced
      inflammasome activation and interleukin (IL)-18 maturation and increased
      susceptibility to colitis and CRC. IL-18 promoted epithelial barrier restitution
      and interferon-gamma production by intestinal CD8+ T cells. Supplementation of IL
      18 or transfer of wild-type myeloid cells reduced tumor burden in AOM-DSS-treated
      Card9-/- and Sykfl/flLysMCre/+ mice, whereas treatment with anti-fungal agents
      exacerbated colitis and CRC. CARD9 deletion changes the gut microbial landscape,
      suggesting that SYK-CARD9 signaling maintains a microbial ecology that promotes
      inflammasome activation and thereby restrains colitis and colon tumorigenesis.

PMID- 30231983
TI  - Germinal Center B Cells Replace Their Antigen Receptors in Dark Zones and Fail
      Light Zone Entry when Immunoglobulin Gene Mutations are Damaging.
AB  - Adaptive immunity involves the development of bespoke antibodies in germinal
      centers (GCs) through immunoglobulin somatic hypermutation (SHM) in GC dark zones
      (DZs) and clonal selection in light zones (LZs). Accurate selection requires that
      cells fully replace surface B cell receptors (BCRs) following SHM, but whether
      this happens before LZ entry is not clear. We found that most GC B cells degrade
      pre-SHM receptors before leaving the DZ, and that B cells acquiring crippling
      mutations during SHM rarely reached the LZ. Instead, apoptosis was triggered
      preferentially in late G1, a stage wherein cells with functional BCRs re-entered
      cell cycle or reduced surface expression of the chemokine receptor CXCR4 to
      enable LZ migration. Ectopic expression of the anti-apoptotic gene Bcl2 was not
      sufficient for cells with damaging mutations to reach the LZ, suggesting that BCR
      dependent cues may actively facilitate the transition. Thus, BCR replacement and
      pre-screening in DZs prevents the accumulation of clones with non-functional
      receptors and facilitates selection in the LZ.

PMID- 30231982
TI  - Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development.
AB  - Successful pregnancy requires carefully-coordinated communications between the
      mother and fetus. Immune cells and cytokine signaling pathways participate as
      mediators of these communications to promote healthy pregnancy. At the same time,
      certain infections or inflammatory conditions in pregnant mothers cause severe
      disease and have detrimental impacts on the developing fetus. In this review, we
      examine evidence for the role of maternal and fetal immune responses affecting
      pregnancy and fetal development, both under homeostasis and following infection.
      We discuss immune responses that are necessary to promote healthy pregnancy and
      those that lead to congenital disorders and pregnancy complications, with a
      particular emphasis on the role of interferons and cytokines. Understanding the
      contributions of the immune system in pregnancy and fetal development provides
      important insights into the pathogenesis underlying maternal and fetal diseases
      and sheds insights on possible targets for therapy.

PMID- 30231987
TI  - Michel Jouvet and "exotic" sleep.
AB  - Michel Jouvet directed my medical thesis on paradoxical sleep in cats obtained in
      1969, and my research on sleep in extreme environments (Antarctica, Arctic winter
      cold, physical exercise), which was the subject of my Ph.D. dissertation in 1984.
      As a military MD and scientist, I was posted in "exotic" (far away) places
      (Antarctica, Canada, Niger) and participated in several remote field trials
      (Canada, Cote d'Ivoire, Congo, Angola). Michel Jouvet supervised my research
      activity, allowing me the use of his laboratory facilities. He co-authored the
      work on sleep in Antarctica in 1987. In 1988, he was invited to Niamey (Niger) to
      preside on the international jury of medical doctorate dissertations. He then
      examined one of my patients with narcolepsy-like sleep attacks, suspect of
      sleeping sickness. Jouvet also co-authored our work on nitric oxide in the rat
      model of sleeping sickness. His scientific curiosity led him to study REM sleep
      eye movements in Bassari people, an isolated ethnic group in Senegal. With
      Monique Gessain, he co-authored a book on the Bassari oneiric activity. He was
      convinced that research in electricity-free villages was capital for
      understanding past mankind story. The present contribution recognizes the
      tremendous work capacity and scientific curiosity of Michel Jouvet.

PMID- 30231988
TI  - Saccadic selection of stabilized items in visuospatial working memory.
AB  - Saccadic eye movements prioritize the memory of visual stimuli that had
      previously been seen at the saccade target. In two experiments, we assessed
      whether this influence is limited to fragile memory traces or if saccades can
      also affect consolidated representations in visuospatial working memory (VSWM).
      To interfere with fragile memory traces, we presented visual masks at different
      delays following the offset of a memory array and simultaneously prompted
      participants to generate a saccade to one location. Masking was very effective:
      Memory performance was lowest right after the disappearance of the memory array
      and gradually increased for later mask onsets. In spite of that, memory was best
      for stimuli congruent with the saccade target. This advantage was largest at
      shortest delays and then decreased over the course of a second. Insofar as only
      consolidated representations survive interference from masks, we conclude that
      saccades exert spatially selective biases on stable representations in VSWM.

PMID- 30231990
TI  - Lack of beneficial effects of low-dose radiation therapy on hand osteoarthritis
      symptoms and inflammation: a randomised, blinded, sham-controlled trial.
AB  - OBJECTIVES: Low-dose radiation therapy (LDRT) is widely used as treatment for
      osteoarthritis (OA) in some countries, while relatively unknown in others.
      Systematic literature review displayed a lack of high-level evidence for
      beneficial effects in clinical practice. The aim was to assess the efficacy of
      LDRT on symptoms and inflammation in hand OA patients in a randomised, blinded,
      sham-controlled trial, using validated outcome measures. DESIGN: Hand OA
      patients, >=50 years, with pain >=5 (scale 0-10) and non-responding to
      conservative therapy were included and randomised 1:1 to receive LDRT (6 * 1 Gy
      in 2 weeks) or sham (6 * 0 Gy in 2 weeks). Primary outcome was the proportion of
      OMERACT-OARSI responders, 3 months post-intervention. Secondary outcomes were
      pain and functioning (Australian/Canadian Hand Osteoarthritis Index; AUSCAN),
      quality of life (Short Form Health Survey; SF36) and inflammatory outcomes:
      erythrocyte sedimentation rate and C-reactive protein serum levels, effusion,
      synovial thickening and power Doppler signal on ultrasound (range 0-3). RESULTS:
      Fifty-six patients were included. After 3 months, no significant difference in
      responders was observed between groups (LDRT: 8 (29%); sham: 10 (36%); difference
      -7% (95%CI -31-17%)). Also, differences in clinical and inflammatory outcomes
      between groups were small and not significant. CONCLUSIONS: We were unable to
      demonstrate a substantial beneficial effect of LDRT on symptoms and inflammation
      in patients with hand OA, compared to sham treatment. Although a small effect can
      not be excluded, a treatment effect exceeding 20% is very unlikely, given the
      confidence interval. Therefore, in the absence of other high-level evidence, we
      advise against the use LDRT as treatment for patients with hand OA. CLINICAL
      TRIAL REGISTRATION NUMBER: NTR4574 (Dutch Trial Register).

PMID- 30231991
TI  - Measurement properties for the revised patient-reported OsteoArthritis Quality
      Indicator questionnaire.
AB  - OBJECTIVES: To assess validity, reliability, responsiveness and interpretability
      of the revised OsteoArthritis Quality Indicator (OA-QI) questionnaire version 2
      (v2) assessing patient-reported quality of osteoarthritis care. METHODS: The OA
      QI v2 (16 items, score range 0-100 (100 = best score)) was included in a
      longitudinal cohort study. Attendees of a 4.5 h osteoarthritis patient education
      programme at Diakonhjemmet Hospital, Norway, completed the OA-QI at four time
      points: 2 weeks before, immediately before, immediately after, and 3 months after
      the programme. Test-retest reliability and measurement error over a 2-week time
      period were assessed in those that had not seen health professionals in the
      interim. Construct validity and responsiveness were assessed with predefined
      hypotheses. Floor and ceiling effects, smallest detectable change (SDC95%) and
      minimal important change (MIC) were assessed to evaluate interpretability.
      RESULTS: The intraclass correlation coefficient for all 16 items was 0.89. For
      single items the test-retest kappa estimates ranged 0.38-0.85 and percent
      agreement 69-92%. Construct validity was acceptable with all six predefined
      hypotheses confirmed. Responsiveness was acceptable with 33 of 48 and three of
      four predefined hypotheses confirmed for single items and all items,
      respectively. There were no floor or ceiling effects. The SDC95% was 29.1 and 3.0
      at the individual and group levels, respectively. MIC was 20.4. CONCLUSIONS: The
      OA-QI v2 had higher reliability estimates compared to v1, showed acceptable
      validity, and is the recommended version for future use. The results of
      responsiveness testing further support the use of the OA-QI v2 as an outcome
      measure in studies aiming to improve osteoarthritis care.

PMID- 30231992
TI  - Mannose Alters Gut Microbiome, Prevents Diet-Induced Obesity, and Improves Host
      Metabolism.
AB  - Mannose is an important monosaccharide for protein glycosylation in mammals but
      is an inefficient cellular energy source. Using a C57BL6/J mouse model of diet
      induced obesity, we show that mannose supplementation of high-fat-diet-fed mice
      prevents weight gain, lowers adiposity, reduces liver steatosis, increases
      endurance and maximal O2 consumption, and improves glucose tolerance. Mannose
      supplemented mice have higher fecal energy content, suggesting reduced caloric
      absorption by the host. Mannose increases the Bacteroidetes to Firmicutes ratio
      in the gut microbiota, a signature associated with the lean phenotype. These
      beneficial effects of mannose are observed when supplementation is started early
      in life. Functional transcriptomic analysis of cecal microbiota revealed profound
      and coherent changes in microbial energy metabolism induced by mannose that are
      predicted to lead to reduced energy harvest from complex carbohydrates by gut
      microbiota. Our results suggest that the gut microbiota contributes to mannose
      induced resistance to deleterious effects of a high-fat diet. VIDEO ABSTRACT.

PMID- 30231993
TI  - Spatial Separation of Mitochondrial Calcium Uptake and Extrusion for Energy
      Efficient Mitochondrial Calcium Signaling in the Heart.
AB  - Mitochondrial Ca2+ elevations enhance ATP production, but uptake must be balanced
      by efflux to avoid overload. Uptake is mediated by the mitochondrial Ca2+
      uniporter channel complex (MCUC), and extrusion is controlled largely by the
      Na+/Ca2+ exchanger (NCLX), both driven electrogenically by the inner membrane
      potential (DeltaPsim). MCUC forms hotspots at the cardiac mitochondria-junctional
      SR (jSR) association to locally receive Ca2+ signals; however, the distribution
      of NCLX is unknown. Our fractionation-based assays reveal that extensively jSR
      associated mitochondrial segments contain a minor portion of NCLX and lack Na+
      dependent Ca2+ extrusion. This pattern is retained upon in vivo NCLX
      overexpression, suggesting extensive targeting to non-jSR-associated
      submitochondrial domains and functional relevance. In cells with non-polarized
      MCUC distribution, upon NCLX overexpression the same given increase in matrix
      Ca2+ expends more DeltaPsim. Thus, cardiac mitochondrial Ca2+ uptake and
      extrusion are reciprocally polarized, likely to optimize the energy efficiency of
      local calcium signaling in the beating heart.

PMID- 30231994
TI  - Autophagy Controls CSL/RBPJkappa Stability through a p62/SQSTM1-Dependent
      Mechanism.
AB  - Cancer-associated fibroblasts (CAFs) are important at all tumor stages.
      CSL/RBPJkappa suppresses the gene expression program leading to CAF activation
      and associated metabolic reprogramming, as well as autophagy. Little is known
      about CSL protein turnover, especially in the tumor microenvironment. We report
      that, in human dermal fibroblasts (HDFs), conditions inducing autophagy-often
      found in tumor stroma-down-regulate CSL protein levels but do not affect its mRNA
      levels. Genetic or pharmacologic targeting of the autophagic machinery blocks CSL
      down-modulation. Mechanistically, endogenous CSL associates with the autophagy
      and signaling adaptor p62/SQSTM1, which is required for CSL down-modulation by
      autophagy. This is functionally significant, because both CSL and p62 levels are
      lower in skin cancer-derived CAFs, in which autophagy is increased. Increasing
      cellular CSL levels stabilizes p62 and down-modulates the autophagic process. We
      reveal here an autophagy-initiated mechanism for CSL down-modulation, which could
      be targeted for stroma-focused cancer prevention and treatment.

PMID- 30231995
TI  - Stiffness-Induced Endothelial DLC-1 Expression Forces Leukocyte Spreading through
      Stabilization of the ICAM-1 Adhesome.
AB  - Leukocytes follow the well-defined steps of rolling, spreading, and crawling
      prior to diapedesis through endothelial cells (ECs). We found increased
      expression of DLC-1 in stiffness-associated diseases like atherosclerosis and
      pulmonary arterial hypertension. Depletion of DLC-1 in ECs cultured on stiff
      substrates drastically reduced cell stiffness and mimicked leukocyte
      transmigration kinetics observed for ECs cultured on soft substrates. Mechanistic
      studies revealed that DLC-1-depleted ECs or ECs cultured on soft substrates
      failed to recruit the actin-adaptor proteins filamin B, alpha-actinin-4, and
      cortactin to clustered ICAM-1, thereby preventing the ICAM-1 adhesome formation
      and impairing leukocyte spreading. This was rescued by overexpressing DLC-1,
      resulting in ICAM-1 adhesome stabilization and leukocyte spreading. Our results
      reveal an essential role for substrate stiffness-regulated endothelial DLC-1,
      independent of its GAP domain, in locally stabilizing the ICAM-1 adhesome to
      promote leukocyte spreading, essential for efficient leukocyte transendothelial
      migration.

PMID- 30231996
TI  - The Drosophila Small Conductance Calcium-Activated Potassium Channel Negatively
      Regulates Nociception.
AB  - Inhibition of nociceptor activity is important for the prevention of spontaneous
      pain and hyperalgesia. To identify the critical K+ channels that regulate
      nociceptor excitability, we performed a forward genetic screen using a Drosophila
      larval nociception paradigm. Knockdown of three K+ channel loci, the small
      conductance calcium-activated potassium channel (SK), seizure, and tiwaz, causes
      marked hypersensitive nociception behaviors. In more detailed studies of SK, we
      found that hypersensitive phenotypes can be recapitulated with a genetically null
      allele. Optical recordings from nociceptive neurons showed a significant increase
      in mechanically activated Ca2+ signals in SK mutant nociceptors. SK is expressed
      in peripheral neurons, including nociceptive neurons. Interestingly, SK proteins
      localize to axons of these neurons but are not detected in dendrites. Our
      findings suggest a major role for SK channels in the regulation of nociceptor
      excitation and are inconsistent with the hypothesis that the important site of
      action is within dendrites.

PMID- 30231997
TI  - Selective NaV1.7 Antagonists with Long Residence Time Show Improved Efficacy
      against Inflammatory and Neuropathic Pain.
AB  - Selective block of NaV1.7 promises to produce non-narcotic analgesic activity
      without motor or cognitive impairment. Several NaV1.7-selective blockers have
      been reported, but efficacy in animal pain models required high multiples of the
      IC50 for channel block. Here, we report a target engagement assay using
      transgenic mice that has enabled the development of a second generation of
      selective Nav1.7 inhibitors that show robust analgesic activity in inflammatory
      and neuropathic pain models at low multiples of the IC50. Like earlier
      arylsulfonamides, these newer acylsulfonamides target a binding site on the
      surface of voltage sensor domain 4 to achieve high selectivity among sodium
      channel isoforms and steeply state-dependent block. The improved efficacy
      correlates with very slow dissociation from the target channel. Chronic dosing
      increases compound potency about 10-fold, possibly due to reversal of
      sensitization arising during chronic injury, and provides efficacy that persists
      long after the compound has cleared from plasma.

PMID- 30231998
TI  - The Locus Coeruleus Modulates Intravenous General Anesthesia of Zebrafish via a
      Cooperative Mechanism.
AB  - How general anesthesia causes loss of consciousness has been a mystery for
      decades. It is generally thought that arousal-related brain nuclei, including the
      locus coeruleus (LC), are involved. Here, by monitoring locomotion behaviors and
      neural activities, we developed a larval zebrafish model for studying general
      anesthesia induced by propofol and etomidate, two commonly used intravenous
      anesthetics. Local lesion of LC neurons via two-photon laser-based ablation or
      genetic depletion of norepinephrine (NE; a neuromodulator released by LC neurons)
      via CRISPR/Cas9-based mutation of dopamine-beta-hydroxylase (dbh) accelerates
      induction into and retards emergence from general anesthesia. Mechanistically, in
      vivo whole-cell recording revealed that both anesthetics suppress LC neurons'
      activity through a cooperative mechanism, inhibiting presynaptic excitatory
      inputs and inducing GABAA receptor-mediated hyperpolarization of these neurons.
      Thus, our study indicates that the LC-NE system plays a modulatory role in both
      induction of and emergence from intravenous general anesthesia.

PMID- 30232000
TI  - Multimodal Enhancement of Remyelination by Exercise with a Pivotal Role for
      Oligodendroglial PGC1alpha.
AB  - Remyelination is a multistep regenerative process that results in the reformation
      of myelin sheaths around demyelinated axons and is a critical therapeutic target.
      Here we show that immediate access to a running wheel following toxin-induced
      demyelination in mice enhances oligodendrogenesis, the rate of remyelination, and
      the proportion of remyelinated axons. RNA sequencing suggests broad activation of
      pro-remyelination pathways including phagocytosis by exercise and highlights
      peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1alpha)
      activation. By immunohistochemistry and cell type-specific conditional deletion,
      we confirmed PGC1alpha within oligodendrocytes as a transiently expressed factor
      required for the rate of myelin thickening by exercise. We validated the exercise
      enhanced clearance of inhibitory lipid debris from lesions. Finally, exercise
      works in parallel with the remyelinating medication clemastine to produce
      complete remyelination of lesions. Our study demonstrates physical activity as an
      integrative means to enhance remyelination and details a multimodal mechanism
      including the pivotal PGC1alpha-dependent enhancement of myelin thickness.

PMID- 30231999
TI  - Sobremesa L-type Amino Acid Transporter Expressed in Glia Is Essential for Proper
      Timing of Development and Brain Growth.
AB  - In Drosophila, ecdysone hormone levels determine the timing of larval
      development. Its production is regulated by the stereotypical rise in
      prothoracicotropic hormone (PTTH) levels. Additionally, ecdysone levels can also
      be modulated by nutrition (specifically by amino acids) through their action on
      Drosophila insulin-like peptides (Dilps). Moreover, in glia, amino-acid-sensitive
      production of Dilps regulates brain development. In this work, we describe the
      function of an SLC7 amino acid transporter, Sobremesa (Sbm). Larvae with reduced
      Sbm levels in glia remain in third instar for an additional 24 hr. These larvae
      show reduced brain growth with increased body size but do not show reduction in
      insulin signaling or production. Interestingly, Sbm downregulation in glia leads
      to reduced Ecdysone production and a surprising delay in the rise of PTTH levels.
      Our work highlights Sbm as a modulator of both brain development and the timing
      of larval development via an amino-acid-sensitive and Dilp-independent function
      of glia.

PMID- 30232001
TI  - Adipose mTORC1 Suppresses Prostaglandin Signaling and Beige Adipogenesis via the
      CRTC2-COX-2 Pathway.
AB  - Beige adipocytes are present in white adipose tissue (WAT) and have thermogenic
      capacity to orchestrate substantial energy metabolism and counteract obesity.
      However, adipocyte-derived signals that act on progenitor cells to control beige
      adipogenesis remain poorly defined. Here, we show that adipose-specific depletion
      of Raptor, a key component of mTORC1, promoted beige adipogenesis through
      prostaglandins (PGs) synthesized by cyclooxygenase-2 (COX-2). Moreover, Raptor
      deficient mice were resistant to diet-induced obesity and COX-2 downregulation.
      Mechanistically, mTORC1 suppressed COX-2 by phosphorylation of CREB-regulated
      transcription coactivator 2 (CRTC2) and subsequent dissociation of CREB to cox-2
      promoter in adipocytes. PG treatment stimulated PKA and promoted differentiation
      of progenitor cells to beige adipocytes in culture. Ultimately, we show that
      pharmacological inhibition or suppression of COX-2 attenuated mTORC1 inhibition
      induced thermogenic gene expression in inguinal WAT in vivo and in vitro. Our
      study identifies adipocyte-derived PGs as key regulators of white adipocyte
      browning, which occurs through mTORC1 and CRTC2.

PMID- 30232002
TI  - Sugar Promotes Feeding in Flies via the Serine Protease Homolog scarface.
AB  - A balanced diet of macronutrients is critical for animal health. A lack of
      specific elements can have profound effects on behavior, reproduction, and
      lifespan. Here, we used Drosophila to understand how the brain responds to
      carbohydrate deprivation. We found that serine protease homologs (SPHs) are
      enriched among genes that are transcriptionally regulated in flies deprived of
      carbohydrates. Stimulation of neurons expressing one of these SPHs, Scarface
      (Scaf), or overexpression of scaf positively regulates feeding on nutritious
      sugars, whereas inhibition of these neurons or knockdown of scaf reduces feeding.
      This modulation of food intake occurs only in sated flies while hunger-induced
      feeding is unaffected. Furthermore, scaf expression correlates with the presence
      of sugar in the food. As Scaf and Scaf neurons promote feeding independent of the
      hunger state, and the levels of scaf are positively regulated by the presence of
      sugar, we conclude that scaf mediates the hedonic control of feeding.

PMID- 30232003
TI  - CARM1 Methylates GAPDH to Regulate Glucose Metabolism and Is Suppressed in Liver
      Cancer.
AB  - Increased aerobic glycolysis is a hallmark of cancer metabolism. How cancer cells
      coordinate glucose metabolism with extracellular glucose levels remains largely
      unknown. Here, we report that coactivator-associated arginine methyltransferase 1
      (CARM1 or PRMT4) signals glucose availability to glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) and suppresses glycolysis in liver cancer cells. CARM1
      methylates GAPDH at arginine 234 (R234), inhibiting its catalytic activity.
      Glucose starvation leads to CARM1 upregulation, further inducing R234
      hypermethylation and GAPDH inhibition. The re-expression of wild-type GAPDH, but
      not of its methylation-mimetic mutant, sustains glycolytic levels. CARM1
      inhibition increases glycolytic flux and glycolysis. R234 methylation delays
      tumor cell proliferation in vitro and in vivo. Compared with normal tissues, R234
      is hypomethylated in malignant clinical hepatocellular carcinoma samples.
      Notably, R234 methylation positively correlates with CARM1 expression in these
      liver cancer samples. Our findings thus reveal that CARM1-mediated GAPDH
      methylation is a key regulatory mechanism of glucose metabolism in liver cancer.

PMID- 30232004
TI  - DeltaNp63alpha Suppresses TGFB2 Expression and RHOA Activity to Drive Cell
      Proliferation in Squamous Cell Carcinomas.
AB  - The transcriptional repressor DeltaNp63alpha is a potent oncogene widely
      overexpressed in squamous cell carcinomas (SCCs) of diverse tissue origins, where
      it promotes malignant cell proliferation and survival. We report here the results
      of a genome-wide CRISPR screen to identify pathways controlling DeltaNp63alpha
      dependent cell proliferation, which revealed that the small GTPase RHOA blocks
      cell division upon DeltaNp63alpha knockdown. After DeltaNp63alpha depletion, RHOA
      activity is increased, and cells undergo RHOA-dependent proliferation arrest
      along with transcriptome changes indicative of increased TGF-beta signaling.
      Mechanistically, DeltaNp63alpha represses transcription of TGFB2, which induces a
      cell cycle arrest that is partially dependent on RHOA. Ectopic TGFB2 activates
      RHOA and impairs SCC proliferation, and TGFB2 neutralization restores cell
      proliferation during DeltaNp63alpha depletion. Genomic data from tumors
      demonstrate inactivation of RHOA and the TGFBR2 receptor and DeltaNp63alpha
      overexpression in more than 80% of lung SCCs. These results reveal a signaling
      pathway controlling SCC proliferation that is potentially amenable to
      pharmacological intervention.

PMID- 30232005
TI  - Regulation of Cellular Heterogeneity and Rates of Symmetric and Asymmetric
      Divisions in Triple-Negative Breast Cancer.
AB  - Differentiation events contribute to phenotypic cellular heterogeneity within
      tumors and influence disease progression and response to therapy. Here, we
      dissect mechanisms controlling intratumoral heterogeneity within triple-negative
      basal-like breast cancers. Tumor cells expressing the cytokeratin K14 possess a
      differentiation state that is associated with that of normal luminal progenitors,
      and K14-negative cells are in a state closer to that of mature luminal cells. We
      show that cells can transition between these states through asymmetric divisions,
      which produce one K14+ and one K14- daughter cell, and that these asymmetric
      divisions contribute to the generation of cellular heterogeneity. We identified
      several regulators that control the proportion of K14+ cells in the population.
      EZH2 and Notch increase the numbers of K14+ cells and their rates of symmetric
      divisions, and FOXA1 has an opposing effect. Our findings demonstrate that
      asymmetric divisions generate differentiation transitions and heterogeneity, and
      identify pathways that control breast cancer cellular composition.

PMID- 30232007
TI  - The Helicase PIF1 Facilitates Resection over Sequences Prone to Forming G4
      Structures.
AB  - DNA breaks are complex lesions that can be repaired either by non-homologous end
      joining (NHEJ) or by homologous recombination (HR). The decision between these
      two routes of DNA repair is a key point of the DNA damage response (DDR) that is
      controlled by DNA resection. The core machinery catalyzing the resection process
      is well established. However, little is known about the additional requirements
      of DNA resection over DNA structures with high complexity. Here, we found
      evidence that the human helicase PIF1 has a role in DNA resection, specifically
      for defined DNA regions, such as those prone to form G-quadruplexes. Indeed, PIF1
      is recruited to the site of DNA damage and physically interacts with proteins
      involved in DNA resection, and its depletion causes DNA damage sensitivity and a
      reduction of HR efficiency. Moreover, G4 stabilization by itself hampers DNA
      resection, a phenomenon suppressed by PIF1 overexpression.

PMID- 30232008
TI  - Loss of PICH Results in Chromosomal Instability, p53 Activation, and Embryonic
      Lethality.
AB  - PICH is a DNA translocase necessary for the resolution of ultrafine anaphase DNA
      bridges and to ensure the fidelity of chromosomal segregation. Here, we report
      the generation of an animal model deficient for PICH that allowed us to
      investigate its physiological relevance. Pich KO mice lose viability during
      embryonic development due to a global accumulation of DNA damage. However,
      despite the presence of chromosomal instability, extensive p53 activation, and
      increased apoptosis throughout the embryo, Pich KO embryos survive until day 12.5
      of embryonic development. The absence of p53 failed to improve the viability of
      the Pich KO embryos, suggesting that the observed developmental defects are not
      solely due to p53-induced apoptosis. Moreover, Pich-deficient mouse embryonic
      fibroblasts exhibit chromosomal instability and are resistant to RASV12/E1A
      induced transformation. Overall, our data indicate that PICH is essential to
      preserve chromosomal integrity in rapidly proliferating cells and is therefore
      critical during embryonic development and tumorigenesis.

PMID- 30232009
TI  - Subtle Changes in the Levels of BCL-2 Proteins Cause Severe Craniofacial
      Abnormalities.
AB  - Apoptotic cell death removes unwanted cells and is regulated by interactions
      between pro-survival and pro-apoptotic members of the BCL-2 protein family. The
      regulation of apoptosis is thought to be crucial for normal embryonic
      development. Accordingly, complete loss of pro-survival MCL-1 or BCL-XL (BCL2L1)
      causes embryonic lethality. However, it is not known whether minor reductions in
      pro-survival proteins could cause developmental abnormalities. We explored the
      rate-limiting roles of MCL-1 and BCL-XL in development and show that combined
      loss of single alleles of Mcl-1 and Bcl-x causes neonatal lethality. Mcl-1+/-;Bcl
      x+/- mice display craniofacial anomalies, but additional loss of a single allele
      of pro-apoptotic Bim (Bcl2l11) restores normal development. These findings
      demonstrate that the control of cell survival during embryogenesis is finely
      balanced and suggest that some human craniofacial defects, for which causes are
      currently unknown, may be due to subtle imbalances between pro-survival and pro
      apoptotic BCL-2 family members.

PMID- 30232006
TI  - Opposing Roles of FANCJ and HLTF Protect Forks and Restrain Replication during
      Stress.
AB  - The DNA helicase FANCJ is mutated in hereditary breast and ovarian cancer and
      Fanconi anemia (FA). Nevertheless, how loss of FANCJ translates to disease
      pathogenesis remains unclear. We addressed this question by analyzing proteins
      associated with replication forks in cells with or without FANCJ. We demonstrate
      that FANCJ-knockout (FANCJ-KO) cells have alterations in the replisome that are
      consistent with enhanced replication stress, including an aberrant accumulation
      of the fork remodeling factor helicase-like transcription factor (HLTF).
      Correspondingly, HLTF contributes to fork degradation in FANCJ-KO cells.
      Unexpectedly, the unrestrained DNA synthesis that characterizes HLTF-deficient
      cells is FANCJ dependent and correlates with S1 nuclease sensitivity and fork
      degradation. These results suggest that FANCJ and HLTF promote replication fork
      integrity, in part by counteracting each other to keep fork remodeling and
      elongation in check. Indicating one protein compensates for loss of the other,
      loss of both HLTF and FANCJ causes a more severe replication stress response.

PMID- 30232010
TI  - Regulation of S100A8 Stability by RNF5 in Intestinal Epithelial Cells Determines
      Intestinal Inflammation and Severity of Colitis.
AB  - Inflammatory bowel disease (IBD) is prevalent, but the mechanisms underlying
      disease development remain elusive. We identify a role for the E3 ubiquitin
      ligase RNF5 in IBD. Intestinal epithelial cells (IECs) express a high level of
      RNF5, while the colon of Rnf5-/- mice exhibits activated dendritic cells and
      intrinsic inflammation. Rnf5-/- mice exhibit severe acute colitis following
      dextran sodium sulfate (DSS) treatment. S100A8 is identified as an RNF5
      substrate, resulting in S100A8 ubiquitination and proteasomal-dependent
      degradation that is attenuated upon inflammatory stimuli. Loss of RNF5 from IECs
      leads to enhanced S100A8 secretion, which induces mucosal CD4+ T cells, resulting
      in Th1 pro-inflammatory responses. Administration of S100A8-neutralizing
      antibodies to DSS-treated Rnf5-/- mice attenuates acute colitis development and
      increases survival. An inverse correlation between RNF5 and S100A8 protein
      expression in IECs of IBD patients coincides with disease severity. Collectively,
      RNF5-mediated regulation of S100A8 stability in IECs is required for the
      maintenance of intestinal homeostasis.

PMID- 30232011
TI  - A Tyrosine Switch on NEDD4-2 E3 Ligase Transmits GPCR Inflammatory Signaling.
AB  - Ubiquitination is essential for protein degradation and signaling and pivotal to
      many physiological processes. Ubiquitination of a subset of G-protein-coupled
      receptors (GPCRs) by the E3 ligase NEDD4-2 is required for p38 activation, but
      how GPCRs activate NEDD4-2 to promote ubiquitin-mediated signaling is not known.
      Here, we report that the GPCR protease-activated receptor-1 (PAR1) stimulates c
      Src-mediated tyrosine phosphorylation and activation of NEDD4-2 to promote p38
      signaling and endothelial barrier disruption. Using mass spectrometry, we
      identified a unique phosphorylated tyrosine (Y)-485 within the 2,3-linker peptide
      between WW domain 2 and 3 of NEDD4-2 in agonist-stimulated cells. Mutation of
      NEDD4-2 Y485 impaired E3 ligase activity and failed to rescue PAR1-stimulated p38
      activation and endothelial barrier permeability. The purinergic P2Y1 receptor
      also required c-Src and NEDD4-2 tyrosine phosphorylation for p38 activation.
      These studies reveal a novel role for c-Src in GPCR-induced NEDD4-2 activation,
      which is critical for driving ubiquitin-mediated p38 inflammatory signaling.

PMID- 30232013
TI  - Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the
      Transcriptional Outcome of Associated Genes.
AB  - Protein arginine methyltransferase 6 (PRMT6) catalyzes asymmetric dimethylation
      of histone H3 at arginine 2 (H3R2me2a). This mark has been reported to associate
      with silent genes. Here, we use a cell model of neural differentiation, which
      upon PRMT6 knockout exhibits proliferation and differentiation defects.
      Strikingly, we detect PRMT6-dependent H3R2me2a at active genes, both at promoter
      and enhancer sites. Loss of H3R2me2a from promoter sites leads to enhanced KMT2A
      binding and H3K4me3 deposition together with increased target gene transcription,
      supporting a repressive nature of H3R2me2a. At enhancers, H3R2me2a peaks co
      localize with the active enhancer marks H3K4me1 and H3K27ac. Here, loss of
      H3R2me2a results in reduced KMT2D binding and H3K4me1/H3K27ac deposition together
      with decreased transcription of associated genes, indicating that H3R2me2a also
      exerts activation functions. Our work suggests that PRMT6 via H3R2me2a interferes
      with the deposition of adjacent histone marks and modulates the activity of
      important differentiation-associated genes by opposing transcriptional effects.

PMID- 30232012
TI  - Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers.
AB  - The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for
      antibody-based prophylactic vaccines. The generation of broadly neutralizing
      antibodies (bNAb) likely requires the appropriate presentation of stabilized
      trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We
      designed a series of membrane-bound Envs with increased trimer stability through
      the introduction of key stabilization mutations. We derived a stabilized HIV-1
      trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding
      while maintaining high quaternary and MPER-specific bNAb binding. Its soluble
      counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like
      Env structure is confirmed by negative stain-EM and glycosylation profiling of
      the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that
      the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have
      successfully designed a stabilized native-like Env trimer amenable to nucleic
      acid or viral vector-based vaccination strategies.

PMID- 30232014
TI  - A Human Adult Stem Cell Signature Marks Aggressive Variants across Epithelial
      Cancers.
AB  - Cancer progression to an aggressive phenotype often co-opts aspects of stem cell
      biology. Here, we developed gene signatures for normal human stem cell
      populations to understand the relationship between epithelial cancers and stem
      cell transcriptional programs. Using a pan-cancer approach, we reveal that
      aggressive epithelial cancers are enriched for a transcriptional signature shared
      by epithelial adult stem cells. The adult stem cell signature selected for
      epithelial cancers with worse overall survival and alterations of oncogenic
      drivers. Lethal small cell neuroendocrine lung, prostate, and bladder cancers
      transcriptionally converged onto the adult stem cell signature and not other stem
      cell signatures tested. We found that DNA methyltransferase expression correlated
      with adult stem cell signature status and was enriched in small cell
      neuroendocrine cancers. DNA methylation analysis uncovered a shared epigenomic
      profile between small cell neuroendocrine cancers. These pan-cancer findings
      establish a molecular link between human adult stem cells and aggressive
      epithelial cancers.

PMID- 30232015
TI  - Treatment of the dens fractures in children.
AB  - : The anatomical and biomechanical features of the immature cervical spine make
      the upper segments at C1-3 especially susceptible to injury. MATERIAL AND METHOD:
      From 2000 to 2016, 10 patients (3 boys, 7 girls) with C2 dens fractures were
      treated. The average age of each child was 11 years (3-17). According to the
      Anderson classification, there were 6 patients with a type III fracture and 4
      with a type II. 4 patients were treated conservatively using the Minerva cervical
      brace for 75 days (66-125) and 6 patients by means of the Halo-Vest for 79 days
      (64-87) and followed by the Schantz collar for 17 days (2-35). RESULTS: The
      follow up lasted 78 months (12-180). The NDI (Neck Disability Index) score was
      calculated for each patient, except for section 8 (driving the car). The scores
      ranged from 1/45 (2.22%) to 20/45 (44.44%). The mean score for 9 out of the 10
      patients (one patient died) was 4.77 (10.61%). CONCLUSION: The C2 dens fracture
      is a rare injury in children. The classification system of dens fractures
      developed by Anderson is useful in choosing the mode of treatment of dens
      fractures.

PMID- 30232016
TI  - A Wedge-Shaped Uncemented Femoral Component: Survivorship in Patients Younger
      Than 50 Years at a Mean Follow-Up of 22 Years.
AB  - BACKGROUND: This study presents the results of the long-term survival of a wedge
      shaped uncemented femoral component in a cohort of young patients with a follow
      up of 20-25 years. METHODS: In a consecutive series of 85 patients (100 hips),
      aged less than 50 years at the time of primary total hip arthroplasty, the long
      term survival of the Cementless Spotorno femoral component was analyzed by
      performing a Kaplan-Meier survival analysis (95% confidence interval [CI]).
      RESULTS: The mean follow-up was 22 years (range, 19.7-25.5). The clinical and
      radiographic outcomes were satisfactory. The overall survival rate of the femoral
      component was 93.4% after 23.8 years (95% CI, 85.9%-97.0%). Survival with
      revision for aseptic loosening as the end point was 94.4% (95% CI, 87.0%-97.6%)
      after 23.8 years. CONCLUSION: This study shows an excellent long-term survival of
      this specific wedge-shaped uncemented femoral component after 20 to 25 years in
      patients younger than 50 years.

PMID- 30232017
TI  - Treatment Modalities for Pathologic Fractures of the Proximal Femur
      Pertrochanteric Region: A Systematic Review and Meta-Analysis of Reoperation
      Rates.
AB  - BACKGROUND: The proximal femur represents the most common site of metastatic bone
      disease in the appendicular skeleton, and associated pathologic pertrochanteric
      femur fractures contribute to cancer-related morbidity and mortality. Controversy
      exists as to whether these injuries are best managed with intramedullary nailing
      (IMN) or with arthroplasty. METHODS: A systematic review of the literature was
      performed using a PubMed search following PRISMA guidelines to identify studies
      performed within the last 20 years regarding treatment of proximal femur
      metastatic lesions with either nailing or arthroplasty with a reported
      reoperation rate. Sixteen studies were selected for inclusion containing 1414
      patients. Pooled estimates and 95% confidence intervals (CIs) for reoperation
      rates associated with IMN and endoprosthetic reconstruction (EPR) were separately
      calculated. RESULTS: The pooled estimate for reoperation for IMN was a median of
      9% (95% CI, 5%-14%) and the pooled estimate for reoperation for EPR was a median
      of 7% (95% CI, 5%-11%). Significant heterogeneity was present in studies
      reporting on both treatment modalities: for IMN, I2 = 55%, and for EPR, I2 = 51%.
      CONCLUSION: This systematic literature review identified 16 eligible,
      nonrandomized, retrospective studies that reported on the results of surgical
      treatment for proximal femur metastatic disease. The pooled estimate of
      reoperation was similar between patients treated with IMN and EPR.
      Inconsistencies among follow-up and the study designs used limited evidence-based
      conclusions. As the oncologic care of patients with metastatic disease continues
      to evolve and improve, patient-specific needs must be carefully considered when
      selecting an optimal treatment strategy. LEVEL OF EVIDENCE: Level III.

PMID- 30232018
TI  - Response to Letter to the Editor on "Comparison of Customized Cutting Block and
      Conventional Cutting Instrument in Total Knee Arthroplasty: A Randomized
      Controlled Trial".

PMID- 30232019
TI  - Toxic effect of triphenyltin in the presence of nano zinc oxide to marine copepod
      Tigriopus japonicus.
AB  - Marine organisms are naturally exposed to different environmental pollutants
      including organic pollutants and nanoparticles. The interactive effects between
      nanoparticles and other chemicals on aquatic organisms have raised concerns
      regarding the potential of nanomaterials as the vector for other chemicals. In
      the present study, the effect of nano zinc oxide (nZnO) on the bioavailability of
      triphenyltin chloride (TPTCl) was studied, and their combined acute and
      reproductive toxicity to the marine copepod Tigriopus japonicus were evaluated.
      At experimental concentration ranges of nZnO in this study, the percentage of
      dissolution of Zn2+ was relative stable (from 62% to 66%), and nZnO did not
      affect the bioavailability of TPTCl to the copepods. The acute toxicity of binary
      mixtures of nZnO/TPT was equivalent to that of the mixture of Zn2+/TPT. In
      agreement with the decrease in TPTCl's LC50 values at the presence of nZnO, their
      interacting effect was synergistic based on response addition response surface
      model, and the interacting parameter was modelled to be -1.43. In addition to
      acute toxicity test, reproductive toxicity tests revealed that exposure to nZnO
      and TPTCl didn't affect the successful mating rate and the number of nauplii in
      the 1st brood, but they extended the time for the eggs to hatch from 2.53 days to
      3.94 and 3.64 days, respectively. The exposure to nZnO/TPTCl mixture delayed the
      time to hatch to 5.78 days.

PMID- 30232020
TI  - Quantitative Hepatic Fat Quantification in Non-alcoholic Fatty Liver Disease
      Using Ultrasound-Based Techniques: A Review of Literature and Their Diagnostic
      Performance.
AB  - Non-alcoholic fatty liver disease is a condition that is characterized by the
      presence of >5% fat in the liver and affects more than one billion people
      worldwide. If adequate and early precautions are not taken, non-alcoholic fatty
      liver disease can progress to cirrhosis and death. The current reference standard
      for detecting hepatic steatosis is a liver biopsy. However, because of the
      potential morbidity associated with liver biopsies, non-invasive imaging
      biomarkers have been extensively investigated. Magnetic resonance imaging-based
      methods have proven accuracy in quantifying liver steatosis; however, these
      techniques are costly and have limited availability. Ultrasound-based
      quantitative imaging techniques are increasingly utilized because of their
      widespread availability, ease of use and relative cost-effectiveness. Several
      ultrasound-based liver fat quantification techniques have been investigated,
      including techniques that measure changes in the acoustic properties of the liver
      caused by the presence of fat. In this review, we focus on quantitative
      ultrasound approaches and their diagnostic performance in the realm of non
      alcoholic fatty liver disease.

PMID- 30232021
TI  - Status of preimplantation genetic testing and embryo selection.
AB  - At the recent 2018 PGDIS congress, a review of randomized controlled trials of
      preimplantation genetic testing for aneuploidies (PGT-A) showed improved ongoing
      pregnancy rates per transfer in experienced centres and in women aged 35 years
      and older. Young women produce 40% abnormal embryos (20-60% range), but not all
      centres see a selection advantage; this indicates the need for more emphasis in
      improving biopsy and case management. Some chromosome abnormalities are
      iatrogenic; PGT-A could, therefore, be used as assisted reproductive technology
      (ART) quality control. Great improvements in non-invasive PGT by testing spent
      media have been reported, ranging from 80-95% concordance with trophectoderm
      biopsy, probably precluding the need for biopsy soon. Mosaicism was widely
      discussed, with PGDIS agreeing to update their guidelines, but continuing to
      recommend prioritizing euploid, followed by mosaic embryos. Techniques to allow
      simultaneous single sample analysis of aneuploidy and inherited mutations are
      improving, but this does not extend to de-novo mutations. Convincing data were
      presented on the efficacy of using endometrial receptivity tests to improve ART
      outcomes adjuvant or independently of PGT-A. Imprinting, CRISPR and cloning were
      also discussed, with a concluding presentation on the first extensive data
      (aneuploidy and morphology) on in-vivo conceived embryos.

PMID- 30232022
TI  - Association of high level of Hs-CRP with in-stent restenosis: A case-control
      study.
AB  - BACKGROUND: In-stent restenosis (ISR) is one adverse outcome of coronary stent
      implantation. Although using drug-eluting stents has reduced the rate of ISR, it
      remains a major problem. Here, we have investigated the relationship between
      several patient characteristics including serum high sensitive C-reactive protein
      (hs-CRP) and ISR. METHODS: This was a case-control study comprising 104
      individuals with ISR and 202 patients without. Baseline characteristics were
      collected using a questionnaire. Fasting blood glucose (FBG), serum triglycerides
      (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and
      serum high sensitivity C-reactive protein (hs-CRP) were measured using commercial
      kits on an auto-analyzer. Data were analyzed using SPSS software and a p value <=
      0.05 was considered significant. RESULTS: Diabetes mellitus (p < 0.001), stent
      type (p = 0.005), serum hs-CRP (p = 0.006), FBG (p = 0.038) and serum TG (p =
      0.039) were significantly associated with ISR. The association between hs-CRP and
      ISR remained significant after adjustment for stent type and DM. For patients
      with a serum hs-CRP <2.64 mg/dL, ISR was only associated with diabetes mellitus
      (p = 0.016); while for individuals with a serum hs-CRP >=2.64 mg/dL, ISR was also
      associated with the presence of diabetes mellitus, serum triglycerides and stent
      type. CONCLUSION: Higher levels of serum hs-CRP were significantly associated
      with the occurrence of ISR.

PMID- 30232023
TI  - The Impact of Social Deprivation on Pediatric PROMIS Health Scores After Upper
      Extremity Fracture.
AB  - PURPOSE: Although social deprivation is acknowledged to influence physical and
      mental health in adults, it is unclear if and how social deprivation influences
      perceived health in children. This study was conducted to evaluate the impact of
      social deprivation on Patient-Reported Outcomes Measurement Information System
      (PROMIS) scores in children presenting for treatment of upper extremity
      fractures. METHODS: This cross-sectional evaluation analyzed data from 975 new
      pediatric patients (8-17 years old) with upper extremity fractures presenting to
      a tertiary orthopedic center between June 1, 2016, and June 1, 2017. They
      completed self-administered PROMIS Computer Adaptive Tests (CATs). The Area
      Deprivation Index was used to quantify social deprivation. Bivariate statistical
      analysis determined the effect of disparate area deprivation (based on most and
      least deprived national quartiles) for the entire population. RESULTS: A total of
      327 children (34%) lived in areas categorized as the most socially deprived
      quartile of the United States, whereas 202 (21%) arrived from homes in the least
      socially deprived quartile. Children in the most deprived quartile had
      significantly worse mean PROMIS Upper Extremity Function, Mobility, Pain
      Interference, and Peer Relations scores than those in the least deprived
      quartile. Significantly more children from the most socially deprived areas were
      black. Patient age, sex, and fracture type were not significantly different
      between patients from the least and the most socially deprived quartiles.
      CONCLUSIONS: Children living in areas of greatest social deprivation report worse
      Upper Extremity Function, Mobility, Pain Interference, and Peer Relations scores
      on self-administered PROMIS CATs than children from areas of least social
      deprivation at presentation for care of upper extremity fractures. The impact of
      social deprivation on perceived health and function is evident before adulthood
      and, therefore, interventions to mitigate this effect should be offered to
      children as well as adults. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 30232025
TI  - Clinical and functional outcomes after curative resection in octogenarians with
      clinical stage I non-small cell lung cancer.

PMID- 30232024
TI  - Mitochondrial - nuclear genetic interaction modulates whole body metabolism,
      adiposity and gene expression in vivo.
AB  - We hypothesized that changes in the mitochondrial DNA (mtDNA) would significantly
      influence whole body metabolism, adiposity and gene expression in response to
      diet. Because it is not feasible to directly test these predictions in humans we
      used Mitochondrial-Nuclear eXchange mice, which have reciprocally exchanged
      nuclear and mitochondrial genomes between different Mus musculus strains. Results
      demonstrate that nuclear-mitochondrial genetic background combination
      significantly alters metabolic efficiency and body composition. Comparative RNA
      sequencing analysis in adipose tissues also showed a clear influence of the mtDNA
      on regulating nuclear gene expression on the same nuclear background (up to a 10
      fold change in the number of differentially expressed genes), revealing that
      neither Mendelian nor mitochondrial genetics unilaterally control gene
      expression. Additional analyses indicate that nuclear-mitochondrial genome
      combination modulates gene expression in a manner heretofore not described. These
      findings provide a new framework for understanding complex genetic disease
      susceptibility.

PMID- 30232027
TI  - Evaluating meniscus allograft transplant using a cost-effectiveness threshold
      analysis.
AB  - BACKGROUND: It is unknown if meniscal allograft transplant (MAT) delays
      progression of osteoarthritis (OA). Cost-effectiveness threshold analysis can
      demonstrate the necessary delay in OA progression required by MAT to be
      considered cost-effective compared to non-operative management. The purpose of
      this study is to identify the efficacy MAT requires in delaying progression to OA
      in previously meniscectomized knees in order to be considered cost-effective
      compared to non-operative treatment. A secondary goal is to demonstrate the
      influence of age and BMI on the required efficacy of MAT for cost-effectiveness.
      METHODS: A Markov model was developed to evaluate the cost-effectiveness of MAT
      compared to non-operative management for patients with prior meniscectomy. Input
      parameters were identified in existing literature. Cost was derived from
      literature and The PearlDiver Patient Records Database. The required rate of OA
      progression was compared across treatment modalities to determine how effective
      MAT is required to be cost-effective. RESULTS: MAT needs to be 31% more effective
      in delaying OA compared to non-operative interventions in order to be cost
      effective. MAT is most cost-effective in 20-29 year-old patients, requiring a 25%
      greater efficacy in delaying OA. Obesity (BMI 30-35) makes MAT less cost
      effective when compared to non-obese patients; however, the difference in
      required efficacy in delaying OA among obese patient when compared to non
      operative management is approximately 10%. CONCLUSIONS: MAT needs to be
      approximately one-third more effective in delaying OA in previously
      meniscectomized knees to be considered cost-effective. Younger, non-obese
      patients have the lowest required efficacy of MAT to be cost-effective.

PMID- 30232026
TI  - Survival of the low contact stress rotating platform total knee replacement is
      influenced by age: 1058 implants with a minimum follow-up of 10 years.
AB  - BACKGROUND: The low contact stress (LCS) mobile-bearing total knee replacement
      (TKR) was designed to minimise polyethylene wear, aseptic loosening and
      osteolysis. However, registry data suggests there is a significantly greater
      revision rate associated. The primary aim of this study was to assess long-term
      survivorship of the LCS TKR performed at a single high-volume centre. Secondary
      aims were to assess survival by mechanism of failure and identify predictors of
      revision. METHODS: During a 13-year period (1993-2006) 1091 LCS TKRs were
      performed by two senior surgeons. Thirty-three with incomplete data were
      excluded. The patients were retrospectively identified from an arthroplasty
      register. Mean age was 69 (range 30-96) years. Five hundred seventy-seven TKRs
      were performed in females, 481 in males. Mean follow-up was 14 years (SD 4.3).
      RESULTS: There were 59 revisions during the study period: 14 (23.7%) for
      infection, 18 (30.5%) for instability, and 27 (45.8%) for polyethylene wear.
      Three hundred ninety-two patients died. All-cause survival at 10 years was 95%
      (95%CI 91.7-98.3) and at 15 years was 93% (95%CI 88.6-97.8). Survival at 10 years
      according to mechanism of failure was: infection 99% (95%CI 94-100%), instability
      98% (95%CI 94-100%), and polyethylene wear 98% (95%CI 92-100). Of the 27 with
      polyethylene wear, only 19 (70.4%) had osteolysis requiring component revision,
      the other eight (29.6%) had polyethylene exchanges. Cox regression analysis
      identified younger age as the only predictor of revision (HR 0.96, 95%CI 0.94
      0.99, p = 0.003), with a four percent decreased risk of revision for each
      increase in year of age. CONCLUSIONS: The LCS TKR demonstrates excellent long
      term survivorship with a low rate of revision for osteolysis, however this risk
      is increased in younger patients.

PMID- 30232028
TI  - Aortic pulsation prevents the development of ossification of anterior
      longitudinal ligament toward the aorta in patients with diffuse idiopathic
      skeletal hyperostosis (DISH) in Japanese: Results of chest CT-based cross
      sectional study.
AB  - BACKGROUND: The development and etiology of diffuse idiopathic skeletal
      hyperostosis (DISH) were far from complete understanding. Even the precise
      mechanism of the development of its typical right-sided ossification of the
      anterior longitudinal ligament (OALL) frequently compared to 'flowing candle
      wax', a hallmark of DISH, remains unknown. METHODS: The participants of this
      study were 261 individuals (31 females and 230 males) diagnosed as DISH according
      to the criteria established by Resnick and Niwayama extracted from a consecutive
      3013 patients who have undergone chest CT for the examination of pulmonary
      diseases in our institute. The patients with previous thoracic spine surgery and
      younger than 15 years old were excluded. Chest CT data were converted to the
      condition suitable for bone evaluation by the software application. The
      positional relationship between thoracic aorta and OALL, the morphology of the
      OALL adjacent to the aorta and the presence of calcification of the aortic wall
      adjacent to the OALL were studied. RESULTS: Of 261 individuals with DISH, we
      found that thoracic aorta was localized adjacent to the OALL (AD-group) in 123
      cases (47%), whereas 138 cases (53%) were not (NAD-group). All OALL in AD-group
      was localized between T6 and T12. The shape of the OALL adjacent to the aorta was
      either flat or concave except for one. No case showed obvious calcification of
      the aortic wall adjacent to the OALL in AD-group. CONCLUSIONS: The aortic
      pulsation might play an important role in inhibit the development of the OALL
      toward the aorta in DISH. It is likely that establishment of the optimal
      condition of the pulsation stress simulating aortic pulsation and its delivery
      system can achieve arresting, slowing the progression and/or changing the
      morphology of the ossified lesions.

PMID- 30232029
TI  - Endoprosthetic proximal femur replacement to transfemoral amputee as a practical
      treatment option: A case report.

PMID- 30232031
TI  - Decabromodiphenyl ether (BDE-209) enhances foam cell formation in human
      macrophages via augmenting Toll-like receptor 4-dependent lipid uptake.
AB  - Growing epidemiological evidence is substantiating an association between
      exposure to persistent organic pollutants (POPs) and incidence of
      atherosclerosis. Decabromodiphenyl ether (BDE-209) is a new POP which presents
      extensively in human populations; whether this contaminant is potentially
      arteriosclerotic remains unclear. In this study, we investigated the effects of
      BDE-209 on macrophage-derived foam cell formation, a hallmark of early
      atherosclerosis, using THP-1-derived macrophages incubated with oxidized low
      density lipoprotein (oxLDL) as a foam cell model. The results showed that 6.25,
      12.5 and 25.0 MUM of BDE-209 significantly enhanced lipid accumulation inside the
      foam cells, in a dose-dependent manner. Further mechanism assays suggested that
      BDE-209 significantly increased the expression of Toll-like receptor 4 (TLR4), a
      signal transducing integral membrane protein mediating lipid uptake in
      macrophages, at both the mRNA and protein levels. In contrast, there was no
      significant changes for several key regulators involving in lipid efflux,
      lipogenesis, and lipid oxidation in macrophages. Furthermore, the augmented lipid
      accumulation was almost completely abrogated by treatment with an anti-TLR4
      antibody. Together, these data illustrate that BDE-209 enhances oxLDL-induced
      macrophage foam cell formation via augmenting TLR4-dependent lipid uptake in the
      cells.

PMID- 30232030
TI  - Biodegradation of ECM hydrogel promotes endogenous brain tissue restoration in a
      rat model of stroke.
AB  - The brain is considered to have a limited capacity to repair damaged tissue and
      no regenerative capacity following injury. Tissue lost after a stroke is
      therefore not spontaneously replaced. Extracellular matrix (ECM)-based hydrogels
      implanted into the stroke cavity can attract endogenous cells. These hydrogels
      can be formulated at different protein concentrations that govern their
      rheological and inductive properties. We evaluated histologically 0, 3, 4 and 8
      mg/mL of porcine-derived urinary bladder matrix (UBM)-ECM hydrogel concentrations
      implanted in a 14-day old stroke cavity. Less concentrated hydrogels (3 and 4
      mg/mL) were efficiently degraded with a 95% decrease in volume by 90 days,
      whereas only 32% of the more concentrated and stiffer hydrogel (8 mg/mL) was
      resorbed. Macrophage infiltration and density within the bioscaffold
      progressively increased in the less concentrated hydrogels and decreased in the 8
      mg/mL hydrogels. The less concentrated hydrogels showed a robust invasion of
      endothelial cells with neovascularization. No neovascularization occurred with
      the stiffer hydrogel. Invasion of neural cells increased with time in all
      hydrogel concentrations. Differentiation of neural progenitors into mature
      neurons with axonal projections was evident, as well as a robust invasion of
      oligodendrocytes. However, relatively few astrocytes were present in the ECM
      hydrogel, although some were present in the newly forming tissue between
      degrading scaffold patches. Implantation of an ECM hydrogel partially induced
      neural tissue restoration, but a more complete understanding is required to
      evaluate its potential therapeutic application. STATEMENT OF SIGNIFICANCE:
      Extracellular matrix hydrogel promotes tissue regeneration in many peripheral
      soft tissues. However, the brain has generally been considered to lack the
      potential for tissue regeneration. We here demonstrate that tissue regeneration
      in the brain can be achieved using implantation of ECM hydrogel into a tissue
      cavity. A structure-function relationship is key to promote tissue regeneration
      in the brain. Specifically, weaker hydrogels that were retained in the cavity
      underwent an efficient biodegradation within 14 days post-implantation to promote
      a tissue restoration within the lesion cavity. In contrast, stiffer ECM hydrogel
      only underwent minor biodegradation and did not lead to a tissue restoration.
      Inductive hydrogels weaker than brain tissue provide the appropriate condition to
      promote an endogenous regenerative response that restores tissue in a cavity.
      This approach offers new avenues for the future treatment of chronic tissue
      damage caused by stroke and other acute brain injuries.

PMID- 30232032
TI  - Betulinic acid protects mice from cadmium chloride-induced toxicity by inhibiting
      cadmium-induced apoptosis in kidney and liver.
AB  - Cadmium exposure is closely associated with a variety of diseases including
      cancers and the accumulation of cadmium has been long recognized as a public
      health problem. It is therefore of high importance to find methods to reduce
      cadmium accumulation in the human body. Herein, we report that administration of
      betulinic acid (BA) protects mice from cadmium chloride (CdCl2)-induced toxicity
      by inhibiting cadmium-induced apoptosis in both kidney and liver. Mice were given
      oral doses of 3 mg/kg, 10 mg/kg and 30 mg/kg of BA daily for ten consecutive
      days, and were injected with one dose of 1 mg/kg CdCl2 after one hour of BA
      administration every day. The levels of serum alanine aminotransferase (ALT),
      aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were assessed by
      ELISA. Residual cadmium was determined by atomic absorption analysis. Protein
      expression was evaluated by western blotting. Pretreatment with BA significantly
      reduced residual cadmium levels in the liver, kidney and testis, increased the
      cadmium output in urine, and reduced tissue damage induced by CdCl2. Moreover, BA
      prevented body weight loss by CdCl2 in a dose dependent manner. Furthermore, BA
      treatment increased the expression levels of B-cell lymphoma 2 (Bcl-2), decreased
      Bcl-2-associated X (Bax), and inhibited the levels of active caspase-3.
      Importantly, BA within a dose of 30 mg/kg did not induce any signs of toxicity,
      and protected mice from the toxicity induced by CdCl2 in a dose-dependent manner.
      Our findings suggest that BA inhibits CdCl2 induced apoptosis in the kidney and
      liver, and BA may be an effective agent for the prevention and treatment of
      cadmium-induced diseases in humans.

PMID- 30232033
TI  - Efficient vitamin B12-imprinted boronate affinity magnetic nanoparticles for the
      specific capture of vitamin B12.
AB  - Vitamin B12 (VB12) has an important function in human physiology. However,
      analysis of VB12 at natural levels in foods or biological samples is difficult
      because of its very low concentration level and the presence of high-abundance
      components which can interfere with the measuring system. Thus, it is essential
      to develop efficient and selective enrichment approaches for VB12. Molecularly
      imprinted polymers (MIPs) have important applications from separation and sensing
      to catalysis. However, there is no report on the preparation of MIPs for VB12.
      Here, we use boronate affinity-based oriented surface imprinting to prepare MIPs
      for VB12. A VB12 template was first covalently immobilized onto the surface of
      boronic acid functionalized magnetic nanoparticles. Subsequently, a thin
      imprinting coating of poly(2-anilinoethanol) was formed to cover the substrate
      surface via in-water polymerization. After removing the template, 3D cavities
      complementary to the molecular size and shape of the template were formed in the
      imprinting layer. The imprinting coating was highly hydrophilic and presented
      limited residual boronic acid, thus non-specific binding was avoided. The
      prepared MIPs exhibited several highly favorable features, including excellent
      specificity, high binding strength and low binding pH. The prepared MIPs were
      successfully applied to the analysis of VB12 in human milk.

PMID- 30232034
TI  - Inflammation and CB2 signaling drive novel changes in the ocular lipidome and
      regulate immune cell activity in the eye.
AB  - Uveitis is inflammation of the uvea which consists of the iris, ciliary body and
      the choroid of the eye. Uveitis can lead to impaired vision and is responsible
      for 10% of all cases of blindness globally. Using an endotoxin-induced uveitis
      (EIU) rodent model, our previous data implicated the endogenous cannabinoid
      system (ECS) in the amelioration of many of the components of the inflammatory
      response. Here, we test the hypothesis that the reduction in inflammatory
      mediators in the EIU model by the CB2 agonist, HU308, is associated with changes
      in ECS endogenous ligands as well as related lipids, prostaglandins (PGs), 2-acyl
      glycerols, and lipoamines. Analysis of leukocytes and neutrophils, CB2 mRNA, and
      26 lipids in the eye of WT mice after EIU induction and HU308 treatment were
      compared to the same analyses in the CB2 knock-out (CB2 KO) mouse. Endothelial
      leukocyte adhesion and neutrophil migration were significantly increased in both
      WT and CB2 KO after EIU. HU308 significantly reduced the leukocyte adhesion and
      neutrophil recruitment in the WT animals. HU308 also significantly reduced
      leukocyte adhesion in the CB2 KO mouse, yet, had no effect on neutrophil
      infiltration suggesting an important off-target effect of HU308. Lipidomics
      profiles revealed significant increases in 6 non-ECS lipids after EIU in the WT
      and that HU308 effectively reduced these back to control levels; in addition,
      HU308 increased levels of 2-acyl glycerols and decreased all N-acyl glycines. CB2
      KOs with saline-injection compared to WT had significantly elevated levels of 2
      acyl glycerols, whereas levels of N-oleoyl ethanolamine (OEA), N-stearoyl
      ethanolamine (SEA), and PGE2 were reduced. CB2 KOs with EIU had 13 lipids that
      were significantly lower than WT with EIU including 4 N-acyl glycines. HU308 had
      no effect on lipid concentrations in the CB2 KOs with EIU, however, it did cause
      further reductions on 3 additional lipids compared to saline controls. HU308
      appears to be acting at a non-CB2 target for the reduction of leukocyte
      infiltration in the EIU model; however, our data suggest that HU308 is working
      through CB2 to reduce neutrophil migration and for the regulation of multiple
      lipid signaling pathways including PGs, lipoamines, and 2-acyl glycerols. These
      data implicate ocular CB2 as a key component of lipid signaling in the eye and
      part of the regulatory processes of inflammation.

PMID- 30232035
TI  - Correlation between chronological and physiological age of males from their
      multivariate urinary endogenous steroid profile and prostatic carcinoma-induced
      deviation.
AB  - The biosynthesis of endogenous androgenic anabolic steroids (EAAS) in males
      varies with age. Knowledge of the general urinary EAAS profile's dependence from
      aging - not reported up to now - may represents a prerequisite for its
      exploitation in the screening and diagnostic support for several pathologies.
      Extended urinary EAAS profiles were obtained from healthy and pathological
      individuals, using a GC-MS method which was fully validated by a stepwise,
      analyst-independent scheme. Seventeen EAAS and five of their concentration ratios
      were determined and investigated using multivariate statistical methods. A
      regression model based on Kernel partial least squares algorithm was built to
      correlate the chronological age of healthy male individuals with their
      "physiological age" as determined from their urinary EAAS profile. Strong
      correlation (R2 = 0.75; slope = 0.747) and good prediction ability of the real
      chronological age was inferred from EAAS data. In contrast, patients with recent
      diagnosis (not pharmacologically treated) of prostatic carcinoma (PCa) exhibited
      a comprehensive EAAS profile with strong negative deviation from the model,
      corresponding a younger predicted age. This result is possibly related to the
      activation of anomalous steroid biosynthesis induced from PCa. Over a restricted
      60-80 years-old population, PLS-discriminant analysis (DA) was used to
      distinguish healthy subjects from patients with untreated PCa. PLS-DA yielded
      excellent discrimination (sensitivity and specificity >90%) between healthy and
      pathological individuals. This proof-of-concept study provides a preliminary
      evaluation of multivariate DA on wide EAAS profiles as a screening method to
      distinguish PCa from non-pathological conditions, overcoming the potentially
      interfering effect of ageing.

PMID- 30232036
TI  - Effect of maternal antioxidant supplementation and/or exercise practice during
      pregnancy on postnatal overnutrition induced by litter size reduction: Brain
      redox homeostasis at weaning.
AB  - Prenatal and early postnatal environments can permanently influence health
      throughout life. Early overnutrition increases the risk to develop chronic
      diseases. Conversely, the intake of flavonoids and exercise practice during
      pregnancy seem to promote long-term benefits to offspring. We hypothesized that
      benefic interventions during pregnancy could protect against possible postnatal
      neurochemical alterations caused by overnutrition induced by reduced litter size.
      Female Wistar rats were divided into four groups: (1) sedentary + vehicle, (2)
      sedentary + naringenin, (3) swimming exercise + vehicle, and (4) swimming
      exercise + naringenin. One day after birth, the litter was culled to 8 pups
      (control) or 3 pups (overfed) per dam, yielding control and overfed subgroups for
      each maternal group. Serum of 21-days-old pups was collected, also the
      cerebellum, hippocampus, and hypothalamus were dissected. Litter size reduction
      increased fat mass and enhanced body weight. Maternal interventions, when
      isolated, caused reduced glucose serum levels in offspring nurtured in control
      litters. In the cerebellum, reducing the litter size decreased the activity of
      thioredoxin reductase, which was prevented by maternal supplementation with
      naringenin. Hippocampus and hypothalamus have shown altered antioxidant enzymes
      activities in response to litter size reduction. Interestingly, when maternal
      exercise and naringenin supplementation were allied, the effect disappeared,
      suggesting a concurrent effect of the two maternal interventions. In conclusion,
      exercise or naringenin supplementation during pregnancy can be important
      interventions for combating the increasing rates of overweight during the infancy
      and its related neurochemical changes, especially when applied isolated.

PMID- 30232037
TI  - The potential role of adenosine signaling in the pathogenesis of melanoma.
AB  - Melanoma cancer cell proliferation, motility, invasion, and tumor growth is
      affected by the adenosine pathway that consists of adenosine-synthesizing
      enzymes, receptors, and their respective agonists/antagonists. Accumulating
      evidence suggests that ischemia and inflammation, two conditions associated with
      melanoma, display dysregulated adenosine metabolism, which implicates it as the
      mechanism responsible for the pathogenesis of melanoma, thereby resulting in
      advanced diagnosis and therapy. Suppression of adenosine signaling by inhibiting
      adenosine receptors or adenosine-generating enzymes (CD39 and CD73) on melanoma
      cells presents a novel therapeutic target for patients with melanoma. This review
      summarizes the role of adenosine signaling in the pathogenesis of melanoma to
      advance its understanding and hence improve therapeutics and management.

PMID- 30232038
TI  - Accounting for stimulus and participant effects in event-related potential
      analyses to increase the replicability of studies.
AB  - BACKGROUND: Event-related potentials (ERPs) are increasingly used in cognitive
      science. With their high temporal resolution, they offer a unique window into
      cognitive processes and their time course. In this paper, we focus on ERP
      experiments whose designs involve selecting participants and stimuli amongst
      many. Recently, Westfall et al. (2017) highlighted the drastic consequences of
      not considering stimuli as a random variable in fMRI studies with such designs.
      Most ERP studies in cognitive psychology suffer from the same drawback. NEW
      METHOD: We advocate the use of the Quasi-F or Mixed-effects models instead of the
      classical ANOVA/by-participant F1 statistic to analyze ERP datasets in which the
      dependent variable is reduced to one measure per trial (e.g., mean amplitude). We
      combine Quasi-F statistic and cluster mass tests to analyze datasets with
      multiple measures per trial. Doing so allows us to treat stimulus as a random
      variable while correcting for multiple comparisons. RESULTS: Simulations show
      that the use of Quasi-F statistics with cluster mass tests allows maintaining the
      family wise error rates close to the nominal alpha level of 0.05. COMPARISON WITH
      EXISTING METHODS: Simulations reveal that the classical ANOVA/F1 approach has an
      alarming FWER, demonstrating the superiority of models that treat both
      participant and stimulus as random variables, like the Quasi-F approach.
      CONCLUSIONS: Our simulations question the validity of studies in which stimulus
      is not treated as a random variable. Failure to change the current standards
      feeds the replicability crisis.

PMID- 30232039
TI  - Improved methods for MRI-compatible implants in nonhuman primates.
AB  - BACKGROUND: Neuroscientists commonly use permanently implanted headposts to
      stabilize the head of nonhuman primates (NHPs) during electrophysiology and
      functional magnetic resonance imaging (fMRI). Here, we present improved
      methodology for MRI-compatible implants without the use of acrylic for head
      stabilization in NHPs. NEW METHOD: MRI is used to obtain a 3D-reconstruction of
      NHP skulls, which are used to create customized implants by modeling
      intersections with the bone. Implants are manufactured from PEEK using computer
      numerical control machining and coated with hydroxyapatite to promote
      osseointegration. Surgically, implants are attached to the skull with ceramic
      screws, while the skin flap is pulled over the implant and closed subcutaneously.
      RESULTS: Quality of blood oxygen level dependent (BOLD) fMRI signal is improved
      in animals implanted with our method as compared to traditional acrylic implants.
      Additionally, implants are well-integrated with the skull, remain robust for more
      than a year and without granulation tissue around the skin margin. COMPARISON
      WITH EXISTING METHOD(S): Previous improvements on NHP implants (Chen et al.,
      2017; McAndrew et al., 2012; Mulliken et al., 2015; Overton et al., 2017) lacked
      fMRI-compatibility, as they relied on titanium headposts and/or titanium screws.
      Thus, most fMRI studies in NHPs today still rely on the use of acrylic-based
      headposts for stabilization and the use of contrast-enhanced agents to improve
      MRI signal. CONCLUSIONS: Our method preserves fMRI-compatibility and results in
      measurable improvement in BOLD signal without the use of contrast-enhanced
      agents. Furthermore, the long-term stability of our implants contributes
      positively to the wellbeing of NHPs in neuroscience research.

PMID- 30232040
TI  - Laryngotracheoesophageal cleft, a rare differential diagnosis of esophageal
      atresia.
AB  - A laryngotracheoesophageal cleft, commonly called laryngeal cleft (LC), is a
      congenital malformation of the posterior part of the larynx creating an abnormal
      communication between the laryngotracheal axis and the pharyngoesophageal axis.
      The prenatal ultrasonographic features associating absent stomach, polyhydramnios
      and mediastinal "pouch sign" are usually considered pathognomonic for esophageal
      atresia. This observation demonstrates that they can also correspond to a severe
      form of laryngotracheoesophageal cleft extending to the carina.

PMID- 30232041
TI  - Beyond Pulmonary Embolism; Nonthrombotic Pulmonary Embolism as Diagnostic
      Challenges.
AB  - Nonthrombotic pulmonary embolism (NTPE) is less well understood and is
      encountered less frequently than pulmonary embolism from venous thrombosis. NTPE
      results from embolization of nonthrombotic material to the pulmonary vasculature
      originating from many different cell types as well as nonbiologic or foreign
      materials. For many radiologists NTPE is a challenging diagnosis, presenting
      nonspecific or unusual imaging findings in the setting of few or unusual clinical
      signs. The aim of this paper is to review the pathophysiology of diverse causes
      of NTPE, which should aid radiologists to better understand and, more
      importantly, diagnose these infrequent events.

PMID- 30232042
TI  - Fear vs. frustration - Possible factors behind canine separation related
      behaviour.
AB  - The signs of separation related problems (SRP) may vary according to the inner
      state that triggers them - for example we found earlier that dogs with owner
      reported SRP were characterized with a predominance of whining during a short
      isolation from the owner, meanwhile barking occurred independently of the owner
      reported SRP status. Based on the theory that the owner represents a resource for
      the dog we hypothesise that there is an association between the permissive and
      inconsistent behaviour of the owner and the reduced frustration threshold in the
      dog, which consequently will show specific signs of SRP. In our study,
      personality traits of the owner and the dog were measured with a questionnaire,
      while the separation behaviour was observed with an outdoor test. We found that
      dogs that rather barked than whined in the separation test had more likely a
      lenient owner. Dogs with owner-reported SRP whined less frequently than non-SRP
      dogs if they had lenient owners. The connection between the owner's
      permissiveness and the type of emitted vocalisation supports the theory that the
      owner's attitude towards the dog can be associated with the dogs' frustration
      related SRP signs as they tend to respond with similar behaviours that occur in
      other frustrating situations.

PMID- 30232043
TI  - Verbal behavior and risky choice in humans: Exploring the boundaries of the
      description-experience gap.
AB  - The description-experience (DE) gap is a tendency to prefer uncertain over
      certain rewards when experienced compared to described. DE gap research typically
      intermixes choice between two gains with choice between two losses. Because
      preference for uncertain gains have been found to increase following experienced
      loss, preference for uncertain gains (and the DE gap) may decrease when gains are
      presented in isolation. Experiment 1 examined the DE gap when participants were
      presented choices between gains (points) in isolation. Experiment 2 examined the
      DE gap when participants were presented with gains in isolation and intermixed
      with point losses. When gains were first contacted in isolation, participants
      chose the uncertain gain more when it was described compared to experienced (a
      reversed DE gap). But, when gains were intermixed with losses, participants chose
      the uncertain gain more when it was experienced compared to described (typical DE
      gap). Additional exposure to intermixed following isolated choices led to a
      typical DE gap, and exposure to isolated following intermixed choices decreased
      the size of the typical DE gap. These results show how choice with experienced or
      described outcomes is influenced by intermixing gains with losses and may reveal
      how the DE gap can be manipulated.

PMID- 30232044
TI  - Pilocarpine/ascorbic acid interaction in the immature brain: Electrophysiological
      and oxidative effects in well-nourished and malnourished rats.
AB  - Ascorbic acid (AA) administration has been associated with neuroprotection
      against oxidative stress, although at high doses it can facilitate oxidation and
      acts like a proconvulsing drug. The pilocarpine-induced epilepsy model has been
      widely studied. However, less is known about the effects of sub-convulsive doses
      of pilocarpine on brain activity in immature animals under normal or deficient
      nutritional conditions. Herein, we investigated the effects of chronic
      pilocarpine administration in a sub-convulsive dose, with or without AA, on the
      excitability-related phenomenon denominated as cortical spreading depression
      (CSD) and levels of lipid peroxidation-induced malondialdehyde in well-nourished
      and malnourished rats. At postnatal days 7-28, rats received no gavage treatment
      (naive group), saline (vehicle group), 45 mg/kg/d of pilocarpine and/or 120
      mg/kg/d of AA. CSD propagation and malondialdehyde levels were analyzed at 34-40
      days. The pilocarpine group presented with lower CSD velocities, while AA groups
      exhibited higher CSD velocities and augmented malondialdehyde levels compared
      with controls. The co-administration of AA partially antagonized the pilocarpine
      CSD effects, but did not revert it to control levels. Malnutrition increased CSD
      amplitude and velocity in comparison to the well-nourished condition. The
      electrocorticogram (ECoG) amplitude increased after CSD (ECoG potentiation) when
      compared with the baseline amplitude before CSD. However, no intergroup
      difference was observed in this CSD-related ECoG potentiation. The results
      support the hypothesis of a pilocarpine/ascorbic acid interaction in the immature
      rat brain and might help further the understanding of this interaction on
      neuronal electrical activity and oxidative stress.

PMID- 30232045
TI  - Clinical and prognostic features of ALS/MND in different phenotypes-data from a
      hospital-based registry.
AB  - OBJECTIVES: To explore the natural history, clinical features, and survival
      relevance of patients presenting with amyotrophic lateral sclerosis/motor neuron
      disease (ALS/MND) with different phenotypes. METHODS: All patients were
      prospectively enrolled in a hospital-based register from 2006 to 2015. Cases were
      classified according to established phenotypes: classic, bulbar, flail arm, flail
      leg, upper motor neuron dominate, respiratory, pure lower motor neuron and pure
      upper motor neuron. Survival was analyzed using Kaplan-Meier curves and Cox
      regression analysis. RESULTS: A total of 1157 patients with complete clinical
      information were registered in the current cohort study. The classic phenotype
      was the most frequent phenotype. The mean age of onset, diagnostic delay, smoking
      status, exposure to pesticides and mean survival time were significantly
      different among different phenotypes. The median survival time was 3.1 years for
      all patients. At the end of the analysis, the 3-year survival rate was 62.1%, the
      5-year survival rate was 39.6%, and the 10-year survival rate was 22.0%. The Cox
      analysis revealed that the disease phenotype was an independent predictor of
      survival (hazard ratio = 0.825, P < 0.001), after adjusting for other factors.
      CONCLUSIONS: This study showed the natural history data of ALS/MND and supported
      the theory that varied disease phenotypes had different clinical, demographic and
      prognostic characteristics, which provided the basis for analysis of future
      management and treatment for ALS/MND. Furthermore, the phenotypic expression of
      ALS/MND with distinctive characteristics is important for providing complementary
      information for identifying the underlying mechanisms of the diseases.

PMID- 30232046
TI  - Fatal exertional rhabdomyolysis. Literature review and our experience in forensic
      thanatology.

PMID- 30232047
TI  - Deep learning and the evaluation of pulmonary fibrosis.

PMID- 30232048
TI  - Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co
      suspension delivery technology versus dual therapies in chronic obstructive
      pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3
      randomised controlled trial.
AB  - BACKGROUND: Inhaled corticosteroids have been used in patients with chronic
      obstructive pulmonary disease (COPD), but the potential benefits of their use in
      triple therapy are not well known. We aimed to compare the efficacy of a triple
      therapy with corresponding dual therapies in symptomatic patients with moderate
      to very severe COPD, without a requirement for a history of exacerbations.
      METHODS: In this double-blind, parallel-group, multicentre phase 3 randomised
      controlled trial, we recruited patients from hospitals and care centres in
      Canada, China, Japan, and the USA. Eligible patients were 40-80 years of age,
      were current or former smokers (with a smoking history of >=10 pack-years), had
      an established clinical history of COPD, and were symptomatic for COPD, despite
      receiving two or more inhaled maintenance therapies for at least 6 weeks before
      screening. We randomly assigned patients (2:2:1:1) using an interactive web
      response system to receive budesonide/glycopyrrolate/formoterol fumarate metered
      dose inhaler 320/18/9.6 MUg (BGF MDI), glycopyrrolate/ formoterol fumarate
      metered-dose inhaler 18/9.6 MUg (GFF MDI), budesonide/formoterol fumarate metered
      dose inhaler 320/9.6 MUg (BFF MDI), or open-label budesonide/formoterol fumarate
      dry-powder inhaler 400/12 MUg (BUD/ FORM DPI). Primary endpoints for the
      Europe/Canada statistical analysis approach were FEV1 area under the curve from 0
      4 h (AUC0-4) for BGF MDI versus BFF MDI and BGF MDI versus BUD/FORM DPI over 24
      weeks; and change from baseline in morning pre-dose trough FEV1 for BGF MDI
      versus GFF MDI and non-inferiority of BFF MDI versus BUD/FORM DPI (margin of -50
      mL from lower bound of 95% CI) over 24 weeks. Comparisons with BUD/FORM DPI were
      made for the Europe/Canada statistical analysis approach only. This study is
      registered with ClinicalTrials.gov, number NCT02497001. FINDINGS: Between Aug 20,
      2015, and Jan 5, 2018, 3047 patients were screened from 215 sites, and 1902 were
      randomly assigned to receive BGF MDI (n=640), GFF MDI (n=627), BFF MDI (n=316),
      or BUD/FORM DPI (n=319). Over 24 weeks, BGF MDI significantly improved FEV1 AUC0
      4 versus BFF MDI (least squares mean difference 104 mL, 95% CI 77 to 131;
      p<0.0001) and BUD/FORM DPI (91 mL, 64 to 117; p<0.0001). BGF MDI also
      significantly improved pre-dose trough FEV1 versus GFF MDI (22 mL, 4 to 39;
      p=0.0139) and was non-inferior to BUD/FORM DPI (-10 mL, -36 to 16; p=0.4390). At
      week 24, patients in the BGF MDI group had a significantly improved FEV1 AUC0-4
      compared with patients receiving BFF MDI (116 mL, 95% CI 80 to 152; p<0.0001);
      there was a non-significant improvement in the change from baseline in morning
      pre-dose trough FEV1 at week 24 versus GFF MDI (13 mL, -9 to 36 mL; p=0.2375).
      The most common treatment-emergent adverse events were nasopharyngitis (n=49 [8%]
      in the BGF MDI group; n=41 [7%] in the GFF MDI group; n=26 [8%] in the BFF MDI
      group; and n=30 [9%] in the BUD/FORM DPI group) and upper respiratory tract
      infection (n=65 [10%]; n=38 [6%]; n=18 [6%]; and n=22 [7%]). Pneumonia incidence
      was low (<2%) and similar across treatments. There were two treatment-related
      deaths, both in the GFF MDI group. INTERPRETATION: BGF MDI was efficacious, well
      tolerated, and could be a more appropriate treatment than the corresponding dual
      therapies for symptomatic patients with moderate to very severe COPD,
      irrespective of exacerbation history. FUNDING: Pearl-a member of the AstraZeneca
      Group.

PMID- 30232049
TI  - Deep learning for classifying fibrotic lung disease on high-resolution computed
      tomography: a case-cohort study.
AB  - BACKGROUND: Based on international diagnostic guidelines, high-resolution CT
      plays a central part in the diagnosis of fibrotic lung disease. In the correct
      clinical context, when high-resolution CT appearances are those of usual
      interstitial pneumonia, a diagnosis of idiopathic pulmonary fibrosis can be made
      without surgical lung biopsy. We investigated the use of a deep learning
      algorithm for provision of automated classification of fibrotic lung disease on
      high-resolution CT according to criteria specified in two international
      diagnostic guideline statements: the 2011 American Thoracic Society
      (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin
      American Thoracic Association (ALAT) guidelines for diagnosis and management of
      idiopathic pulmonary fibrosis and the Fleischner Society diagnostic criteria for
      idiopathic pulmonary fibrosis. METHODS: In this case-cohort study, for algorithm
      development and testing, a database of 1157 anonymised high-resolution CT scans
      showing evidence of diffuse fibrotic lung disease was generated from two
      institutions. We separated the scans into three non-overlapping cohorts (training
      set, n=929; validation set, n=89; and test set A, n=139) and classified them
      using 2011 ATS/ERS/JRS/ALAT idiopathic pulmonary fibrosis diagnostic guidelines.
      For each scan, the lungs were segmented and resampled to create a maximum of 500
      unique four slice combinations, which we converted into image montages. The final
      training dataset consisted of 420 096 unique montages for algorithm training. We
      evaluated algorithm performance, reported as accuracy, prognostic accuracy, and
      weighted kappa coefficient (kappaw) of interobserver agreement, on test set A and
      a cohort of 150 high-resolution CT scans (test set B) with fibrotic lung disease
      compared with the majority vote of 91 specialist thoracic radiologists drawn from
      multiple international thoracic imaging societies. We then reclassified high
      resolution CT scans according to Fleischner Society diagnostic criteria for
      idiopathic pulmonary fibrosis. We retrained the algorithm using these criteria
      and evaluated its performance on 75 fibrotic lung disease specific high
      resolution CT scans compared with four specialist thoracic radiologists using
      weighted kappa coefficient of interobserver agreement. FINDINGS: The accuracy of
      the algorithm on test set A was 76.4%, with 92.7% of diagnoses within one
      category. The algorithm took 2.31 s to evaluate 150 four slice montages (each
      montage representing a single case from test set B). The median accuracy of the
      thoracic radiologists on test set B was 70.7% (IQR 65.3-74.7), and the accuracy
      of the algorithm was 73.3% (93.3% were within one category), outperforming 60
      (66%) of 91 thoracic radiologists. Median interobserver agreement between each of
      the thoracic radiologists and the radiologist's majority opinion was good
      (kappaw=0.67 [IQR 0.58-0.72]). Interobserver agreement between the algorithm and
      the radiologist's majority opinion was good (kappaw=0.69), outperforming 56 (62%)
      of 91 thoracic radiologists. The algorithm provided equally prognostic
      discrimination between usual interstitial pneumonia and non-usual interstitial
      pneumonia diagnoses (hazard ratio 2.88, 95% CI 1.79-4.61, p<0.0001) compared with
      the majority opinion of the thoracic radiologists (2.74, 1.67-4.48, p<0.0001).
      For Fleischner Society high-resolution CT criteria for usual interstitial
      pneumonia, median interobserver agreement between the radiologists was moderate
      (kappaw=0.56 [IQR 0.55-0.58]), but was good between the algorithm and the
      radiologists (kappaw=0.64 [0.55-0.72]). INTERPRETATION: High-resolution CT
      evaluation by a deep learning algorithm might provide low-cost, reproducible,
      near-instantaneous classification of fibrotic lung disease with human-level
      accuracy. These methods could be of benefit to centres at which thoracic imaging
      expertise is scarce, as well as for stratification of patients in clinical
      trials. FUNDING: None.

PMID- 30232050
TI  - Symptomatic COPD: is it time for triple therapy?

PMID- 30232051
TI  - Validity and sensitivity to change of the Somatic Symptom Disorder-B Criteria
      Scale (SSD-12) in a clinical population.
AB  - OBJECTIVE: The SSD-12 is a brief self-report questionnaire to measure the
      psychological criteria of DSM-5 Somatic Symptom Disorder. This study examines its
      psychometric properties in a German inpatient sample from a psychosomatic
      rehabilitation setting, and provides evidence to its sensitivity to change.
      METHOD: Patients completed the SSD-12 and the Health49-subscale on somatoform
      complaints before and after receiving inpatient treatment. Therapists evaluated
      the psychological improvement of their patients at the end of treatment. Effect
      sizes (ES) and standardized response means (SRM) of pre- and post-SSD-12 mean
      changes were calculated for subgroups of patients who did or did not improve.
      RESULTS: SSD-12 scores at discharge were significantly lower compared to scores
      at admission for subgroups of patients who improved according to clinicians
      (t=2976, df=103, p=.004), and for patients who improved according to self-report
      (t=5.059, df=159, p<.001). Effect sizes of change in SSD-12 scores in the
      improved subgroups were ES=-0.19 and ES=-0.30, and standardized response means
      were SRM=-0.29 and SRM=-0.40, respectively. CONCLUSION: The SSD-12 shows sound
      psychometric properties and is useful and time-efficient for monitoring
      psychological burden associated with bothersome somatic symptoms. Its sensitivity
      to change over time could be documented.

PMID- 30232052
TI  - Woman-centered care: Women's experiences and perceptions of induction of labor
      for uncomplicated post-term pregnancy: A systematic review of qualitative
      evidence.

PMID- 30232053
TI  - Ambivalence in digital health: Co-designing an mHealth platform for HIV care.
AB  - In reaction to polarised views on the benefits or drawbacks of digital health,
      the notion of 'ambivalence' has recently been proposed as a means to grasp the
      nuances and complexities at play when digital technologies are embedded within
      practices of care. This article responds to this proposal by demonstrating how
      ambivalence can work as a reflexive approach to evaluate the potential
      implications of digital health. We first outline current theoretical advances in
      sociology and organisation science and define ambivalence as a relational and
      multidimensional concept that can increase reflexivity within innovation
      processes. We then introduce our empirical case and highlight how we engaged with
      the HIV community to facilitate a co-design space where 97 patients (across five
      European clinical sites: Antwerp, Barcelona, Brighton, Lisbon, Zagreb) were
      encouraged to lay out their approaches, imaginations and anticipations towards a
      prospective mHealth platform for HIV care. Our analysis shows how patients
      navigated ambivalence within three dimensions of digital health: quantification,
      connectivity and instantaneity. We provide examples of how potential tensions
      arising through remote access to quantified data, new connections with care
      providers or instant health alerts were distinctly approached alongside embodied
      conditions (e.g. undetectable viral load) and embedded socio-material
      environments (such as stigma or unemployment). We conclude that ambivalence can
      counterbalance fatalistic and optimistic accounts of technology and can support
      social scientists in taking-up their critical role within the configuration of
      digital health interventions.

PMID- 30232054
TI  - Causes of early rebleeding after coil embolization of ruptured cerebral
      aneurysms.
AB  - OBJECTIVE: Early rebleeding after coil embolization of a ruptured cerebral
      aneurysm is rare but may cause severe disability or death. We present a case
      series of early rebleeding after coil embolization of ruptured cerebral aneurysms
      and investigate the incidence, clinical outcome and possible mechanism through
      retrospective analysis of angiographic and surgical findings. PATIENTS AND
      METHODS: This study included 347 consecutive patients who had undergone
      successful coil embolization of 347 ruptured cerebral saccular aneurysms.
      Clinical and angiographic data and findings from emergent surgery were analyzed
      retrospectively. RESULTS: Early rebleeding occurred in eight aneurysms (2.3%) and
      was especially frequent among anterior communicating artery lesions (6 out of
      122, 4.9%). The other two events involved posterior communication artery lesions.
      The maximum diameter of the aneurysms that developed early rebleeding was 4.89 +/
      0.65 mm, ranging from 3.9 to 5.7 mm. In seven out of eight patients, the
      immediate radiologically determined occlusion status was a residual neck, and the
      remaining patient had a residual sac. The coil packing density was between 21%
      and 34%. Six cases of rebleeding were detected within 48 h, 1 case was detected
      on the 5th day, and 1 case was detected on the 10th day. Coil compaction was not
      detected by follow-up angiography after early rebleeding. We performed surgical
      clipping as a rescue procedure in 5 cases and additional coil embolization in 1
      case. During follow-up angiography and rescue clipping, inflow of blood to the
      aneurysm was detected in 6 cases. Three patients died, and the other 3 patients
      were severely disabled. The mechanisms of early rebleeding were divided into two
      types. First, blood may flow into the rupture site through a gap between the coil
      mesh and the aneurysm neck. Second, blood may enter the rupture site through the
      coil mesh due to insufficient thrombus formation. CONCLUSIONS: The early
      rebleeding rate after coil embolization of ruptured cerebral aneurysms in our
      study was 2.3%. The ruptured aneurysms were small in size (<6 mm), and rupture
      frequently occurred in the anterior communicating artery. In most cases, inflow
      of blood to the aneurysm was detected by follow-up angiography or during rescue
      surgery.

PMID- 30232055
TI  - Influence of wideband visible light with an padding red component on the
      functional state of mice embryos and embryonic stem cells.
AB  - It is known that visible light, including sunlight and laboratory lighting,
      adversely affect the development of embryos in vitro. In with article we present
      a technology for the synthesis of composite screens, capable to photoconvert UV
      and a part of the blue spectrum into red light with the maximum ~630 nm. It is
      established that the application of such transformed light with an evident red
      component raises the chances of embryos to survive and protects embryonic stem
      cells. To create photoconversion screens, the CdZn/Se quantum dots were obtained,
      the average size being about 7 nm. When the quantum dots are excited by
      electromagnetic waves of the UV and blue spectral range, photoluminescence is
      observed. The average photon energy for photoluminescence is of the order of 2
      eV. On the basis of CdZn/Se quantum dots and methylphenylsiloxane polymer, light
      transforming composite screens were made. In case of the light-transforming
      composite screen, the UV component disappeared from the energy spectrum, and the
      intensity of the blue region of the spectrum was reduced. On the contrary, in the
      red region (lambdamax = 630 nm) one can see a little more than two-fold increase
      of intensity. It is shown that when exposed to 2-cell embryos by transformed
      light, the proportion of normally developing embryos increases by 20%, the number
      of dead embryos decreases twice, and number of dead and apoptotic cells was lower
      in blastocysts, what's decreased by 70%, as compared to the control group. When
      blastocysts are transferred to the feeder substrate, colonies of embryonic stem
      cells are formed. Cells obtained from blastocysts irradiated with transformed
      visible light are in a normal state in 90% of cases and did not change expression
      levels, biochemistry and morphology for at least 20 passages. It is assumed that
      the data obtained can be used for the design of systems of efficient cultivation
      of embryonic cells for tissue engineering and cell therapy.

PMID- 30232056
TI  - Abrupt versus gradual cessation of steroids in patients with septic shock.
AB  - PURPOSE: To determine if a difference in hemodynamic stability would be
      identified in patients with abrupt withdrawal of steroids compared to patients
      who underwent a taper. MATERIAL AND METHODS: This retrospective cohort study
      identified patients who received vasopressors followed by IV hydrocortisone for
      treatment of septic shock from January 1, 2013 until January 1, 2015.The primary
      endpoint evaluated the percent of patients requiring vasopressor re-initiation
      during taper and 72 h following taper, or 72 h directly following abrupt
      withdrawal. Secondary endpoints evaluated include glycemic control, and ICU
      length of stay. RESULTS: A total of 87 patients were included for final analysis.
      Of the 87 patients, 7 out of 41 patients (17.1%) in the steroid taper group
      developed hemodynamic instability and required re-initiation of vasopressors
      compared to 1 out of 46 patients (2.2%) in the abrupt withdrawal group (p =
      0.024). Patients in the taper group also had worse glycemic control (125.1 mg/dL
      abrupt vs. 150.8 taper; p < 0.001). There was no statistical difference found in
      the ICU length of stay (8.28 days abrupt vs.10.73 taper; p = 0.14). CONCLUSION:
      The abrupt withdrawal of steroids in patients with resolving septic shock did not
      impact hemodynamic stability and offers an opportunity to reduce medication
      burden and reduce adverse drug reactions.

PMID- 30232057
TI  - High correlation between mechanical properties and bone mineral parameters in
      embalmed femurs after long-term storage.
AB  - BACKGROUND: Fresh frozen human femurs are considered "the gold standard" in
      biomechanical studies of hip fractures, resembling the in vivo situation mostly.
      A more readily available alternative is formalin embalmed femurs. However, to
      which extent formalin affects key features of bone; its mechanical properties,
      bone mineral content and their mutual relationship over time, remains unknown.
      Accordingly, we measured the mineral parameters and related them to the
      mechanical properties of formalin fixed femurs after long-term storage. METHODS:
      36 paired femurs from human donors, fixed in formalin and stored for a mean
      period of 4.6 (3.5-6) years. Quantitative CT was performed to measure the bone
      mineral density and mass at the mainly cortical mid shaft and the center of the
      mainly cancellous condyles. Each pair was subjected to local tests by three-point
      bending and screw pullout of the shaft and lateral punch and metaphyseal cube
      compression of the condyles. FINDINGS: Neither mechanical nor bone mineral data
      were significantly correlated to storage time. Well-known associations for bone
      parameters with age and gender were retrieved. Maximum force of the cortical bone
      tests was highly correlated to the diaphyseal bone mass; (r = 0.80-0.87, p =
      0.01), while maximum force of the cancellous bone tests correlated well to the
      density of the condylar bone; (r = 0.70, p = 0.01). INTERPRETATION: Our results
      indicate that mechanical and bone mineral data and their mutual relationship are
      conserved in formalin fixed femurs even after long-term storage. Formalin fixed
      femurs may serve as an alternative to fresh frozen femurs in biomechanical
      testing.

PMID- 30232059
TI  - Workshop examines drug shortage solutions during disasters.

PMID- 30232058
TI  - Blowing the whistle: Perceptions of surgical staff and medical students in a
      public South African hospital.
AB  - Understanding perspectives on whistleblowing is important in tackling a
      resistance to speaking out. This study aimed to elicit the views of medical
      students and doctors in Edendale Hospital, South Africa using a mixed-methods
      questionnaire study incorporating free text and tick-box answers. Thematic
      analysis and descriptive statistics were used to interpret the results. Fifty
      eight doctors and medical students responded (87% response rate); the majority
      were surgeons at Edendale hospital. Seventeen percent did not understand the
      concept of whistleblowing, while 42% felt unable to report an adverse event.
      Motivation for reporting adverse events was overwhelmingly in the interests of
      patient safety (91%), but reluctance was mainly due to the potential consequences
      on workplace relationships (24%). The most common innovation suggested was a
      reporting structure (54%). These observations indicate workplace relationships
      are an important barrier to whistleblowing. Further research should expand on
      these concerns and explore staff knowledge about whistleblowing.

PMID- 30232060
TI  - The Academy of Nutrition and Dietetics, corporate sponsorship and the
      alternative: dietitians for professional integrity.

PMID- 30232061
TI  - Exertional heat stress-induced gastrointestinal perturbations: prevention and
      management strategies.

PMID- 30232062
TI  - Advice to athletes with back pain-get active! Seriously?

PMID- 30232063
TI  - Ban on sale of energy drinks to children.

PMID- 30232065
TI  - Artists refuse to take bed blocking lying down.

PMID- 30232066
TI  - Doctors choose Google Translate to communicate with patients because of easy
      access.

PMID- 30232064
TI  - An Estrogen-Related Dietary Pattern and Postmenopausal Breast Cancer Risk in a
      Cohort of Women with a Family History of Breast Cancer.
AB  - Background: The results of previous studies on diet and postmenopausal breast
      cancer risk have been inconclusive, but there is some evidence that dietary
      patterns developed to correlate with estrogen levels are associated with breast
      cancer. We aimed to examine the association of a previously developed estrogen
      related dietary pattern (ERDP) with postmenopausal breast cancer in the Sister
      Study.Methods: The ERDP was calculated from food frequency questionnaire
      responses among Sister Study participants without a personal history of cancer
      and who contributed postmenopausal person-time at risk. Cox proportional hazards
      models were used to estimate HRs and 95% confidence intervals for the association
      between the ERDP and postmenopausal breast cancer.Results: With more than 261,959
      person-years of follow-up and 1,968 incident cases, the ERDP was not associated
      with total, invasive, estrogen receptor (ER)-positive or ER-negative subtypes of
      breast cancer. Results were robust to various sensitivity analyses.Conclusions:
      The results do not support previous studies observing a positive association
      between a proestrogenic dietary pattern and postmenopausal breast cancer risk.
      Null results may be partially explained by high levels of other breast cancer
      risk factors within the study population, such as a family history of breast
      cancer.Impact: An estrogen-related dietary pattern may not be a strong predictor
      of breast cancer risk in all populations. Future studies of diet and breast
      cancer should evaluate the potential for effect modification by family history
      and consider differences in dietary assessment tools when comparing results
      across study populations. Cancer Epidemiol Biomarkers Prev; 27(10); 1223-6.
      (c)2018 AACR.

PMID- 30232067
TI  - MRI SPACE sequence confirmation of occluded MCA M2 dissection stump masquerading
      as a ruptured MCA aneurysm.
AB  - Intracranial vascular pathologies often have overlapping clinical presentations.
      Dissected vessel occlusions and bifurcation aneurysms can appear similar on
      pretherapeutic imaging. The medical management of these two entities is
      drastically different. The patient is a 51-year-old man who presented with
      severe, sudden-onset headache. Initial presentation was consistent with a
      ruptured middle cerebral artery (MCA) aneurysm and surgical clipping was
      recommended. However, further review of radiographic findings could not
      definitively differentiate an aneurysmal origin of the symptoms as opposed to
      intracranial dissection followed by occlusion of the M2 branch of the MCA. MRI
      sampling perfection with application optimised contrasts using different flip
      angle evolution (SPACE) was performed and showed thin flow signalling distal to
      the dissected vessel stump confirming the diagnosis. Accurate diagnosis is a
      crucial step in directing treatment for intracranial vascular lesions. MRI SPACE
      is a simple tool in the diagnostic armamentarium to adequately direct treatment
      and avoid the potential for unnecessary interventions.

PMID- 30232068
TI  - Primary intratracheal schwannoma resected during bronchoscopy using argon plasma
      coagulation.
AB  - A 63-year-old man presented with intermittent, progressively worsening dyspnoea
      associated with cough and blood-tinged sputum. Initial work-up showed left axis
      deviation on ECG, chest X-ray with an elevated left hemidiaphragm and a non
      contrast CT chest that showed a multilobulated mass in the proximal trachea.
      Bronchoscopy showed a whitish-appearing lesion, which was then sampled and
      partially resected with pathology showing a schwannoma with no malignant cells.
      He felt partial relief post procedure; however, he presented a month later with
      similar symptoms of dyspnoea and a repeat CT scan showed enlargement of the mass
      in the same location. The patient underwent another flexible bronchoscopy and
      resection with argon plasma coagulation (APC)/electrocautery snare.
      APC/electrocautery is an effective interventional bronchoscopy technique that can
      be used to resect endoluminal lesions or extraluminal lesions that have
      infiltrated into the airway using flexible/rigid bronchoscopy. It is more cost
      effective, safe, works well with vascular lesions and achieves excellent
      haemostasis as compared with Nd:YAG lasers.

PMID- 30232069
TI  - Dental management of a patient with 22q11.2 deletion syndrome (22q11.2DS).
AB  - 22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion
      syndromes, with an incidence of approximately 1/2000-1/4000 live births; it is
      thought to be mainly attributable to a de novo deletion. The clinical phenotype
      of this syndrome is highly variable. Certain craniofacial and oral features are
      common to most patients with 22q11.2DS, including a high prevalence of dental
      caries; abnormalities of tooth shape, eruption and number; and enamel defects
      such as hypomineralisation and hypoplasia. This report focuses on the dental
      features and management of an 8-year-old boy with 22q11.2DS. Dental treatments
      were carried out under general anaesthesia. In summary, facial dysmorphism and
      common dental manifestations are typically noticeable in patients with this
      syndrome. Therefore, dentists need to be aware of the dental features of this
      condition in order to refer them to the adequate specialists. Cooperation among
      and experience with different specialties are mandatory to improve quality of
      life for patients with 22q11.2DS.

PMID- 30232070
TI  - A case of young diabetes and parasuicide.
AB  - Wolfram syndrome is a rare monogenic cause of juvenile onset diabetes mellitus.
      It is a non-autoimmune, insulin-deficient state with concurrent or consequent
      optic atrophy. Here we depict the case of a 16-year-old young girl afflicted with
      this condition, who presented with parasuicide on a background of depressive
      disorder. The aetiology of this presentation was attributable to multiple
      physical ailments and a genetic predisposition conferred by the disease-causing
      mutation for which she tested positive. She was managed with intensive insulin
      therapy and specific psychotherapy. Her case highlights the importance of
      recognising and addressing these comorbidities associated with Wolfram syndrome,
      so as to curtail disastrous consequences.

PMID- 30232071
TI  - Custom 3D-printed finger proximal phalanx as salvage of limb function after
      aggressive recurrence of giant cell tumour.
AB  - Giant cell tumours (GCT) of the finger phalanges are extremely rare but have a
      high rate of recurrence. This report details the case of a GCT of the proximal
      phalanx of the fourth finger in a 64-year-old man. The patient was initially
      subjected to systemic neoadjuvant denosumab treatment, and subsequent aggressive
      curettage, sparing of the articular joints, local cryotherapy and autologous
      intercalary fibular bone graft. Finger function after surgery was considered
      satisfactory, despite limited proximal interphalangeal (PIP) joint motion.
      Aggressive local GCT recurrence was noted at the 32-month follow-up, with entire
      articular and diaphyseal phalangeal destruction. The patient refused amputation
      and, after analysing several reconstruction options, he was treated by entire en
      bloc resection and reconstruction employing a 3D-printed custom titanium implant.
      At the 24-month follow-up, the patient is free of disease and pain, and has a
      stable finger, good metacarpal-phalangeal joint motion, fusion of the PIP joint,
      a good Musculoskeletal Tumour Society score, and functional ability.

PMID- 30232072
TI  - Severe pulmonary hypertension associated with hepatic arteriovenous malformation
      in a patient with hereditary haemorrhagic telangiectasia.
AB  - We report a case of 46-year-old Asian woman with a history of recurrent epistaxis
      who presented with dyspnoea on exertion. Physical examination revealed
      mucocutaneous telangiectasias and signs of heart failure. Further evaluation
      showed huge hepatic arteriovenous malformation and severe pulmonary hypertension.
      This case demonstrates an uncommon manifestation of hereditary haemorrhagic
      telangiectasia presented with severe pulmonary hypertension.

PMID- 30232073
TI  - Cutaneous angioleiomyoma of the auricle: a painless variant of a painful tumour.
AB  - Cutaneous angioleiomyomas (ALMs) are uncommon benign tumours of the skin which
      derive from the smooth muscle layer of dermal blood vessels. They usually present
      as tender nodules in the fifth or sixth decade of life, predominantly in the legs
      of females. These tumours rarely present on the head and neck, especially the
      ear. Head and neck ALMs differ from their more common leg counterparts in that
      they are painless. Additionally, they do not manifest with a female predominance.
      Herein, a new case of a painless auricular ALM in a 63-year-old man is reported.

PMID- 30232074
TI  - Subperiosteal haematoma of the orbit secondary to frontal sinusitis.
AB  - Reported is the case of a 79-year-old woman initially diagnosed with periorbital
      abscess on the background of a recent upper respiratory tract infection.
      Unexpectedly, intraoperative findings were that of a haematoma rather than an
      abscess. Subperiosteal orbital haematoma (SOH) is an extremely rare complication
      of rhinosinusitis. In contrast to the more common periorbital abscess, it is
      seldom listed as a complication of sinusitis. A review of reported cases suggests
      an older patient demographic are affected by SOH in contrast to periorbital
      abscess which typically affects paediatric patients. Given current demographic
      trends toward an older patient population with multiple comorbidities, failure to
      consider SOH as a differential will have important implications on preoperative
      workup, perioperative care and final outcome for patients. We present this case
      as a reminder of a rare but important complication of a common disease.

PMID- 30232075
TI  - A rare cause of ascites in a renal transplant recipient.
AB  - Thirty-five-year-old man, underwent renal transplantation 4 years back and was
      doing well. He now presented with complaints of ascites with engorged neck veins
      and dyspnoea on exertion for last 6 months. Examination showed elevated jugular
      venous pressure with two prominent descents, high pitched diastolic heart sound
      (pericardial knock). Echocardiography showed characteristic features of thickened
      pericardium, septal bounce, expiratory flow reversal in hepatic veins and phasic
      variation of mitral inflow, suggestive of constrictive pericarditis. The patient
      was started on empirical antitubercular therapy and diuretics. The patient
      symptomatically improved, but in view of persisting constrictive physiology he
      was planned for pericardiectomy.

PMID- 30232076
TI  - Suspicious breast pseudocalcifications.

PMID- 30232077
TI  - Genitalia self-mutilation commanded by hallucinations: a psychointensive case of
      Klingsor syndrome.

PMID- 30232078
TI  - Primary peritoneal hepatoid adenocarcinoma: a diagnostic and therapeutic
      conundrum in patients with gastrointestinal bleeding.

PMID- 30232080
TI  - Endogenous bacterial endophthalmitis and subretinal abscess complicating diabetic
      ketoacidosis.

PMID- 30232079
TI  - Mid-ventricular takotsubo cardiomyopathy triggered by major depressive disorder
      after abortion.

PMID- 30232081
TI  - The NHS heart age test will overload GPs who are already under huge pressure.

PMID- 30232082
TI  - Association between maternal gluten intake and type 1 diabetes in offspring:
      national prospective cohort study in Denmark.
AB  - OBJECTIVE: To examine the association between prenatal gluten exposure and
      offspring risk of type 1 diabetes in humans. DESIGN: National prospective cohort
      study. SETTING: National health information registries in Denmark. PARTICIPANTS:
      Pregnant Danish women enrolled into the Danish National Birth Cohort, between
      January 1996 and October 2002, MAIN OUTCOME MEASURES: Maternal gluten intake,
      based on maternal consumption of gluten containing foods, was reported in a 360
      item food frequency questionnaire at week 25 of pregnancy. Information on type 1
      diabetes occurrence in the participants' children, from 1 January 1996 to 31 May
      2016, were obtained through registry linkage to the Danish Registry of Childhood
      and Adolescent Diabetes. RESULTS: The study comprised 101 042 pregnancies in 91
      745 women, of whom 70 188 filled out the food frequency questionnaire. After
      correcting for multiple pregnancies, pregnancies ending in abortions,
      stillbirths, lack of information regarding the pregnancy, and pregnancies with
      implausibly high or low energy intake, 67 565 pregnancies (63 529 women) were
      included. The average gluten intake was 13.0 g/day, ranging from less than 7
      g/day to more than 20 g/day. The incidence of type 1 diabetes among children in
      the cohort was 0.37% (n=247) with a mean follow-up period of 15.6 years (standard
      deviation 1.4). Risk of type 1 diabetes in offspring increased proportionally
      with maternal gluten intake during pregnancy (adjusted hazard ratio 1.31 (95%
      confidence interval 1.001 to 1.72) per 10 g/day increase of gluten). Women with
      the highest gluten intake versus those with the lowest gluten intake (>=20 v <7
      g/day) had double the risk of type 1 diabetes development in their offspring
      (adjusted hazard ratio 2.00 (95% confidence interval 1.02 to 4.00)). CONCLUSIONS:
      High gluten intake by mothers during pregnancy could increase the risk of their
      children developing type 1 diabetes. However, confirmation of these findings are
      warranted, preferably in an intervention setting.

PMID- 30232083
TI  - Fallopian Tube Lesions in Women at High Risk for Ovarian Cancer: A Multicenter
      Study.
AB  - The prognosis of women diagnosed with invasive high-grade serous ovarian
      carcinoma (HGSC) is poor. More information about serous tubal intraepithelial
      carcinoma (STIC) and serous tubal intraepithelial lesions (STIL), putative
      precursor lesions of HGSC, could inform prevention efforts. We conducted a
      multicenter study to identify risk/protective factors associated with STIC/STILs
      and characterize p53 signatures in the fallopian tube. The fallopian tubes and
      ovaries of 479 high-risk women >=30 years of age who underwent bilateral risk
      reducing salpingo-oophorectomy were reviewed for invasive cancer/STICs/STILs.
      Epidemiologic data was available for 400 of these women. In 105 women, extensive
      sampling of the tubes for STICs/STILs/p53 signatures were undertaken. Descriptive
      statistics were used to compare groups with and without lesions. The combined
      prevalence of unique tubal lesions [invasive serous cancer (n = 6) /STICs (n =
      14)/STILs (n = 5)] was 6.3% and this was split equally among BRCA1 (3.0%) and
      BRCA2 mutation carriers (3.3%). A diagnosis of invasive cancer was associated
      with older age but no risk/protective factor was significantly associated with
      STICs/STILs. Extensive sampling identified double the number of STICs/STILs
      (11.9%), many p53 signatures (27.0%), and multiple lesions in 50% of the cases.
      Women with p53 signatures in the fimbria were older than women with signatures in
      the remaining tube (P = 0.03). STICs/STILs may not share the protective factors
      that are associated with HGSC. It is plausible that these factors are only
      associated with STICs that progress to HGSC. Having multiple lesions in the
      fimbria may be an important predictor of disease progression. Cancer Prev Res;
      11(11); 697-706. (c)2018 AACR.

PMID- 30232084
TI  - Public Health England's capture by the alcohol industry.

PMID- 30232085
TI  - Platelet heterogeneity in activation-induced glycoprotein shedding: functional
      effects.
AB  - The platelet receptors glycoprotein Ibalpha (GPIbalpha) and GPVI are known to be
      cleaved by members of a disintegrin and metalloprotease (ADAM) family (ADAM10 and
      ADAM17), but the mechanisms and consequences of this shedding are not well
      understood. Our results revealed that (1) glycoprotein shedding is confined to
      distinct platelet populations showing near-complete shedding, (2) the
      heterogeneity between (non)shed platelets is independent of agonist type but
      coincides with exposure of phosphatidylserine (PS), and (3) distinct pathways of
      shedding are induced by elevated Ca2+, low Ca2+ protein kinase C (PKC), or
      apoptotic activation. Furthermore, we found that receptor shedding reduces
      binding of von Willebrand factor, enhances binding of coagulation factors, and
      augments fibrin formation. In response to Ca2+-increasing agents, shedding of
      GPIbalpha was abolished by ADAM10/17 inhibition but not by blockage of calpain.
      Stimulation of PKC induced shedding of only GPIbalpha, which was annulled by
      kinase inhibition. The proapoptotic agent ABT-737 induced shedding, which was
      caspase dependent. In Scott syndrome platelets that are deficient in Ca2+
      dependent PS exposure, shedding occurred normally, indicating that PS exposure is
      not a prerequisite for ADAM activity. In whole-blood thrombus formation, ADAM
      dependent glycoprotein shedding enhanced thrombin generation and fibrin
      formation. Together, these findings indicate that 2 major activation pathways can
      evoke ADAM-mediated glycoprotein shedding in distinct platelet populations and
      that shedding modulates platelet function from less adhesive to more
      procoagulant.

PMID- 30232088
TI  - Mike Lean: Many mountains to climb.

PMID- 30232086
TI  - Engineered FVIII-expressing cytotoxic T cells target and kill FVIII-specific B
      cells in vitro and in vivo.
AB  - Hemophilia A is an X-linked bleeding disorder caused by mutations in the factor
      VIII (FVIII) gene (F8). Treatment with recombinant or plasma-derived FVIII
      replacement therapy is standard therapy. A major problem in treating hemophilia A
      patients with therapeutic FVIII is that 20% to 30% of these patients produce
      neutralizing anti-FVIII antibodies (inhibitors) because they are not
      immunologically tolerant to this human protein. Hence, there is a need to
      establish tolerogenic protocols to FVIII epitopes. To specifically target FVIII
      specific B cells, we engineered immunodominant FVIII domains (A2 and C2) as a
      chimeric antigen receptor expressed by both human and murine cytotoxic T cells.
      This FVIII domain engineered B-cell antibody receptor (BAR) that expresses T
      cells was capable of killing FVIII-reactive B-cell hybridomas in vitro and in
      vivo. Moreover, FVIII BAR CD8 T cells blocked the development of specific
      antibody from unimmunized spleen cells stimulated polyclonally with
      lipopolysaccharide in vitro. In addition, adoptive transfer of FVIII A2- and C2
      BAR CD8 T cells significantly reduced the anti-FVIII antibody formation in
      hemophilic mice. These data suggest that BAR-engineered T cells are a promising
      approach for future prophylactic treatment for patients with severe hemophilia A
      who are at high risk of developing inhibitors.

PMID- 30232089
TI  - Diagnostic expansion in clinical trials: myocardial infarction, stroke, cancer
      recurrence, and metastases may not be the hard endpoints you thought they were.

PMID- 30232087
TI  - Phenotype description and response to thrombopoietin receptor agonist in DIAPH1
      related disorder.

PMID- 30232090
TI  - How to succeed as an academic cardiologist: a conversation for the aspiring
      cardiology trainee.

PMID- 30232091
TI  - Helping Postpartum Women in Mali Achieve Their Fertility Intentions: Perspectives
      From Introduction of the Dedicated Postpartum IUD Inserter.
AB  - BACKGROUND: Mali has one of the highest maternal mortality ratios in the world
      coupled with one of the lowest modern contraceptive use rates. Nearly a quarter
      of the country's 750,000 annual births occur within 24 months of a previous
      birth, increasing the risks for mothers and babies. Nearly 70% of postpartum
      women have an unmet need for family planning. In 2016, Population Services
      International Mali (PSI-Mali) introduced a dedicated postpartum intrauterine
      device (PPIUD) inserter to replace the technique of using forceps for PPIUD
      insertion, with the aim of helping to address this substantial family planning
      gap. METHODS: A mixed-methods approach was used to assess program results and the
      experiences of PSI-trained providers using the dedicated PPIUD inserter in 5
      health facilities in Bamako. We conducted 10 key informant interviews with
      providers and 4 key informant interviews with operational and clinical staff
      involved in training and supporting providers. Further data were collected from
      district health surveys and facility registers. Secondary data encompassed
      documentation from 2011 through 2017, with the service delivery figures of PPIUD
      using the dedicated inserter focused on the pilot period of March 2016 through
      December 2017. Primary data were collected in Mali in July 2017. RESULTS: Between
      March 2016 and December 2017, PSI-Mali trained 134 providers on the dedicated
      PPIUD inserter and provided more than 3,500 voluntary PPIUDs. Of the 1,840
      voluntary PPIUDs provided in 2017 alone, 67% were provided by facilities trained
      to use the dedicated PPIUD inserter. Providers stated a preference for the
      inserter (compared with the use of forceps) due to its ease, speed, and perceived
      lower associated risks of infection. Service data from the 5 facilities visited
      showed an overall average PPIUD uptake of 7.3% of deliveries in 2017. Although
      private facilities had considerably fewer deliveries than public facilities (600
      900 compared with 20-30, respectively), a much higher proportion of women
      delivering in the private facilities chose a PPIUD. CONCLUSION: The acceptance of
      the dedicated PPIUD inserter by providers may help reduce some of the supply-side
      barriers that inhibit women's access to postpartum family planning methods. With
      continued support to providers, coupled with ongoing efforts to address
      differences in service trends between sectors and demand-side barriers to the
      PPIUD and family planning more broadly, the dedicated PPIUD inserter could play
      an important role in responding to the high unmet need among postpartum women in
      Mali.

PMID- 30232093
TI  - 3D airway model to assess airway dead space.
AB  - High flow therapy works partly by washout of airway dead space, the volume of
      which has not been quantified in newborns. This observational study aimed to
      quantify airway dead space in infants and to compare efficacy of washout between
      high flow devices in three-dimensional (3D) printed airway models of infants
      weighing 2.5-3.8 kg. Nasopharyngeal airway dead space volume was 1.5-2.0 mL/kg in
      newborns. A single cannula device produced lower carbon dioxide (CO2) levels than
      a dual cannula device (33.7, 31.2, 23.1, 15.9, 10.9 and 6.3 mm Hg vs 36.8, 35.5,
      32.1, 26.8, 23.1 and 18.8 mm Hg at flow rates of 1, 2, 3, 4, 6 and 8 L/min,
      respectively; p<0.0001 at all flow rates). Airway pressure was 1 mm Hg at all
      flow rates with the single cannula but increased at higher flow rates with the
      dual cannula.Relative nasopharyngeal airway dead space volume is increased in
      newborns. In 3D-printed airway models, a single cannula high flow device produces
      improved CO2 washout with lower airway pressure.

PMID- 30232092
TI  - DNA polymerase epsilon-dependent modulation of the pausing property of the CMG
      helicase at the barrier.
AB  - The proper pausing of replication forks at barriers on chromosomes is important
      for genome integrity. However, the detailed mechanism underlying this process has
      not been well elucidated. Here, we successfully reconstituted fork-pausing
      reactions from purified yeast proteins on templates that had binding sites for
      the LacI, LexA, and/or Fob1 proteins; the forks paused specifically at the
      protein-bound sites. Moreover, although the replicative helicase Cdc45-Mcm2-7
      GINS (CMG) complex alone unwound the protein-bound templates, the unwinding of
      the LacI-bound site was impeded by the presence of a main leading strand DNA
      polymerase: polymerase epsilon (Polepsilon). This suggests that Polepsilon
      modulates CMG to pause at these sites.

PMID- 30232094
TI  - Targeting glucose control in preterm infants: pilot studies of continuous glucose
      monitoring.
AB  - OBJECTIVE: Hyperglycaemia is common in very preterm infants and is associated
      with adverse outcomes. Preventing hyperglycaemia without increasing the risk of
      hypoglycaemia is difficult. Real time tracking with continuous glucose monitors
      (CGM) may improve glucose control. We assessed the feasibility and safety of CGM
      to target glucose control in preterm infants, to inform a randomised controlled
      trial (RCT). DESIGN: We performed a single centre study in very preterm infants
      during the first week of life. Accuracy was assessed by comparison of CGM with
      blood glucose levels (n=20 infants). In a separate pilot study of efficacy
      (n=20), real-time CGM combined with a paper guideline to target glucose control
      (2.6-10 mmol/L) was compared with standard neonatal care (masked CGM).
      Questionnaires were used to assess staff acceptability. RESULTS: No concerns were
      raised about infection or skin integrity at sensor site. The sensor performed
      well compared with point-of-care blood glucose measurements, mean bias of -0.27
      (95% CI -0.35 to -0.19). Per cent time in target range (sensor glucose 2.6-10
      mmol/L) was greater with CGM than POC (77% vs 59%, respectively) and per cent
      time sensor glucose >10 mmol/L was less with CGM than POC (24% vs 40%,
      respectively). The CGM also detected clinically unsuspected episodes of
      hypoglycaemia. Staff reported that the use of the CGM positively improved
      clinical care. CONCLUSIONS: This study suggests that CGM has sufficient accuracy
      and utility in preterm infants to warrant formal testing in a RCT.

PMID- 30232096
TI  - Public health experts split over deal with industry funded charity.

PMID- 30232097
TI  - Up and away: ontogenic transference as a pathway for aerial dispersal of
      microplastics.
AB  - Microplastics (MPs) are ubiquitous pollutants found in marine, freshwater and
      terrestrial ecosystems. With so many MPs in aquatic systems, it is inevitable
      that they will be ingested by aquatic organisms and be transferred up through the
      food chain. However, to date, no study has considered whether MPs can be
      transmitted by means of ontogenic transference, i.e. between life stages that use
      different habitats. Here, we determine whether fluorescent polystyrene beads
      could transfer between Culex mosquito life stages and, particularly, could move
      into the flying adult stage. We show for the first time that MPs can be
      transferred ontogenically from a feeding (larva) into a non-feeding (pupa) life
      stage and subsequently into the adult terrestrial life stage. However,
      transference is dependent on particle size, with smaller 2 um MPs transferring
      readily into pupae and adult stages, while 15 um MPs transferred at a
      significantly reduced rate. MPs appear to accumulate in the Malpighian tubule
      renal excretion system. The transfer of MPs to the adults represents a potential
      aerial pathway to contamination of new environments. Thus, any organism that
      feeds on terrestrial life phases of freshwater insects could be impacted by MPs
      found in aquatic ecosystems.

PMID- 30232098
TI  - Reduction of leucocyte cell surface disulfide bonds during immune activation is
      dynamic as revealed by a quantitative proteomics workflow (SH-IQ).
AB  - Communication through cell surface receptors is crucial for maintaining immune
      homeostasis, coordinating the immune response and pathogen clearance. This is
      dependent on the interaction of cell surface receptors with their ligands and
      requires functionally active conformational states. Thus, immune cell function
      can be controlled by modulating the structure of either the receptor or the
      ligand. Reductive cleavage of labile disulfide bonds can mediate such an
      allosteric change, resulting in modulation of the immune system by a hitherto
      little studied mechanism. Identifying proteins with labile disulfide bonds and
      determining the extent of reduction is crucial in elucidating the functional
      result of reduction. We describe a mass spectrometry-based method-thiol
      identification and quantitation (SH-IQ)-to identify, quantify and monitor such
      reduction of labile disulfide bonds in primary cells during immune activation.
      These results provide the first insight into the extent and dynamics of labile
      disulfide bond reduction in leucocyte cell surface proteins upon immune
      activation. We show that this process is thiol oxidoreductase-dependent and
      mainly affects activatory (e.g. CD132, SLAMF1) and adhesion (CD44, ICAM1)
      molecules, suggesting a mechanism to prevent over-activation of the immune system
      and excessive accumulation of leucocytes at sites of inflammation.

PMID- 30232099
TI  - Quantifying the phosphorylation timescales of receptor-ligand complexes: a
      Markovian matrix-analytic approach.
AB  - Cells interact with the extracellular environment by means of receptor molecules
      on their surface. Receptors can bind different ligands, leading to the formation
      of receptor-ligand complexes. For a subset of receptors, called receptor tyrosine
      kinases, binding to ligand enables sequential phosphorylation of intra-cellular
      residues, which initiates a signalling cascade that regulates cellular function
      and fate. Most mathematical modelling approaches employed to analyse receptor
      signalling are deterministic, especially when studying scenarios of high ligand
      concentration or large receptor numbers. There exist, however, biological
      scenarios where low copy numbers of ligands and/or receptors need to be
      considered, or where signalling by a few bound receptor-ligand complexes is
      enough to initiate a cellular response. Under these conditions stochastic
      approaches are appropriate, and in fact, different attempts have been made in the
      literature to measure the timescales of receptor signalling initiation in
      receptor-ligand systems. However, these approaches have made use of numerical
      simulations or approximations, such as moment-closure techniques. In this paper,
      we study, from an analytical perspective, the stochastic times to reach a given
      signalling threshold for two receptor-ligand models. We identify this time as an
      extinction time for a conveniently defined auxiliary absorbing continuous time
      Markov process, since receptor-ligand association/dissociation events can be
      analysed in terms of quasi-birth-and-death processes. We implement algorithmic
      techniques to compute the different order moments of this time, as well as the
      steady-state probability distribution of the system. A novel feature of the
      approach introduced here is that it allows one to quantify the role played by
      each kinetic rate in the timescales of signal initiation, and in the steady-state
      probability distribution of the system. Finally, we illustrate our approach by
      carrying out numerical studies for the vascular endothelial growth factor and one
      of its receptors, the vascular endothelial growth factor receptor of human
      endothelial cells.

PMID- 30232102
TI  - Association between bronchopulmonary dysplasia and cerebral palsy in children: a
      meta-analysis.
AB  - OBJECTIVE: To investigate the association between bronchopulmonary dysplasia
      (BPD) and the risk of cerebral palsy (CP) in children. DATA SOURCES: We used
      EMBASE, PubMed and Web of Science to conduct a meta-analysis of studies published
      before 1 September 2017, written in English whose titles or abstracts discussed
      an association between BPD and CP. STUDY SELECTION: Observational studies, for
      example, case-control and cohort studies were included. DATA EXTRACTION AND
      SYNTHESIS: All review stages were conducted by two reviewers independently. Data
      synthesis was undertaken via meta-analysis of available evidence. MAIN OUTCOMES
      AND MEASURES: The prevalence of developing CP was measured after exposure to BPD.
      RESULTS: Among 1234 initially identified studies, we selected those that
      addressed an association between BPD and CP according to our preselected
      inclusion criteria. Our meta-analysis included 11 studies. According to a random
      effect model, BPD was significantly associated with CP (ORs 2.10; 95% CI 1.57 to
      2.82) in preterm infants. Factors explaining differences in the study results
      included study design, the definition of BPD, the time of diagnosis of CP and
      whether the studies adjusted for potential confounders. CONCLUSION: This study
      suggests that BPD is a risk factor for CP. Further studies are required to
      confirm these results and to detect the influence of variables across studies.

PMID- 30232103
TI  - Defining the prevalence and symptom burden of those with self-reported severe
      chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a two-phase
      community pilot study in the North East of England.
AB  - OBJECTIVES: To define the prevalence of severe chronic fatigue syndrome/myalgic
      encephalomyelitis (CFS/ME) and its clinical characteristics in a geographically
      defined area of Northern England. To understand the feasibility of a community
      based research study in the severely affected CFS/ME group. DESIGN: A two-phase
      clinical cohort study to pilot a series of investigations in participants own
      homes. SETTING: Participants were community living from the area defined by the
      Northern clinical network of the UK. PARTICIPANTS: Adults with either a medical
      or a self-reported diagnosis of CFS/ME. Phase 1 involved the creation of a
      database. Phase 2: five participants were selected from database, dependent on
      their proximity to Newcastle. INTERVENTIONS: The De Paul fatigue questionnaire
      itemised symptoms of CFS/ME, the Barthel Functional Outcome Measure and
      demographic questions were collected via postal return. For phase 2, five
      participants were subsequently invited to participate in the pilot study.
      RESULTS: 483 questionnaire packs were requested, 63 were returned in various
      stages of completion. 56 De Paul fatigue questionnaires were returned: all but 12
      met one of the CFS/ME criteria, but 12 or 22% of individuals did not fulfil the
      Fukuda nor the Clinical Canadian Criteria CFS/ME diagnostic criteria but 6 of
      them indicated that their fatigue was related to other causes and they barely had
      any symptoms. The five pilot participants completed 60% of the planned visits.
      CONCLUSIONS: Severely affected CFS/ME individuals are keen to participate in
      research, however, their symptom burden is great and quality of life is poor.
      These factors must be considered when planning research and methods of engaging
      with such a cohort.

PMID- 30232100
TI  - Emerging mechanisms of asymmetric stem cell division.
AB  - The asymmetric cell division of stem cells, which produces one stem cell and one
      differentiating cell, has emerged as a mechanism to balance stem cell self
      renewal and differentiation. Elaborate cellular mechanisms that orchestrate the
      processes required for asymmetric cell divisions are often shared between stem
      cells and other asymmetrically dividing cells. During asymmetric cell division,
      cells must establish asymmetry/polarity, which is guided by varying degrees of
      intrinsic versus extrinsic cues, and use intracellular machineries to divide in a
      desired orientation in the context of the asymmetry/polarity. Recent studies have
      expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing
      the previously unappreciated complexity in setting up the cellular and/or
      environmental asymmetry, ensuring binary outcomes of the fate determination. In
      this review, we summarize recent progress in understanding the mechanisms and
      regulations of asymmetric stem cell division.

PMID- 30232101
TI  - UPA-seq: prediction of functional lncRNAs using differential sensitivity to UV
      crosslinking.
AB  - While a large number of long noncoding RNAs (lncRNAs) are transcribed from the
      genome of higher eukaryotes, systematic prediction of their functionality has
      been challenging due to the lack of conserved sequence motifs or structures.
      Assuming that some lncRNAs function as large ribonucleoprotein complexes and thus
      are easily crosslinked to proteins upon UV irradiation, we performed RNA-seq
      analyses of RNAs recovered from the aqueous phase after UV irradiation and phenol
      chloroform extraction (UPA-seq). As expected, the numbers of UPA-seq reads mapped
      to known functional lncRNAs were remarkably reduced upon UV irradiation.
      Comparison with ENCODE eCLIP data revealed that lncRNAs that exhibited greater
      decreases upon UV irradiation preferentially associated with proteins containing
      prion-like domains (PrLDs). Fluorescent in situ hybridization (FISH) analyses
      revealed the nuclear localization of novel functional lncRNA candidates,
      including one that accumulated at the site of transcription. We propose that UPA
      seq provides a useful tool for the selection of lncRNA candidates to be analyzed
      in depth in subsequent functional studies.

PMID- 30232104
TI  - Sarcopenic obesity associated with high-sensitivity C-reactive protein in age and
      sex comparison: a two-center study in South Korea.
AB  - OBJECTIVES: To evaluate the association between high-sensitivity C-reactive
      protein (hs-CRP) and sarcopenic obesity, and to determine age or sex differences
      underlying the relationship between hs-CRP and sarcopenic obesity. DESIGN:
      Observational study. PARTICIPANTS: The study included 237 838 participants whose
      body composition and hs-CRP were analysed at the two health promotion centres in
      South Korea. Participants were divided into four groups based on body
      composition: normal, obesity only, sarcopenia only and sarcopenic obesity.
      PRIMARY MEASURES: The levels of hs-CRP and proportion of participants with high
      (>=1.0 mg/L) hs-CRP. Sarcopenic obesity was defined as subjects fulfilling the
      criteria for sarcopenia (below 2 SD of mean of Skeletal Muscle Mass Index for
      young adults) and obesity (waist circumference >=90 cm for men and >=85 cm for
      women). RESULTS: The level of hs-CRP was highest in the sarcopenic obesity group.
      Following adjustment for various confounders including age, sex, comorbidities,
      metabolic, health-related behaviour and demographic factors, the adjusted ORs
      (95% CI) for subjects with high hs-CRP associated with obesity, sarcopenia and
      sarcopenic obesity compared with normal group (reference) were 1.17 (1.05 to
      1.31), 2.23 (1.21 to 4.07) and 3.23 (2.71 to 3.83), respectively. In age subgroup
      analyses, multivariate logistic regression analysis revealed that the association
      of high hs-CRP with sarcopenic obesity was stronger in younger (<60 years)
      participants than in older (>=60 years) participants (p for interaction <0.001).
      In subgroup analyses for sex, the association of high hs-CRP with sarcopenic
      obesity was higher in female participants than in males (p for interaction
      <0.001). CONCLUSIONS: This study demonstrated that high level of hs-CRP was
      independently associated with sarcopenic obesity in Korean population. We found
      for the first time that there was a strong association between increased hs-CRP
      and sarcopenic obesity in female and younger (<60 years) subjects.

PMID- 30232105
TI  - Effect of vitamin D supplementation on serum 25-hydroxyvitamin D concentration in
      children and adolescents: a systematic review and meta-analysis protocol.
AB  - INTRODUCTION: The importance of vitamin D for bone health as well as its role in
      non-skeletal functions has long been documented. However, review investigations
      on the effect of vitamin D supplementation on serum 25-hydroxyvitamin D (25(OH)D)
      levels in children and adolescents are scarce. The aims of the current study were
      to assess the impact of various doses of vitamin D supplementation on serum
      25(OH)D concentrations in children and adolescents, and to identify relevant
      determinants of variations in the effect of vitamin D supplementation. METHODS:
      PubMed, Scopus, ISI Web of Science and Cochrane Central Register of Controlled
      Trials databases up to 27 September 2017 will systematically be searched for
      randomised controlled trials of vitamin D supplementation. We considered articles
      with the following control groups as eligible: placebo control, control group
      without any supplementation or a comparative arm investigation. Two reviewers
      will assess articles for eligibility according to prespecified selection
      criteria, after which data extraction and quality appraisal will be conducted by
      two independent reviewers. The quality assessment will be assessed using the
      Jadad scale. Meta-analyses will be conducted where appropriate. We will express
      continuous measures (ie, serum 25(OH)D concentration) as mean differences with
      95% CIs. Heterogeneity of the data will be investigated via visual inspection of
      the forest plots and using chi2 test on N-1 df, with a significance level of
      alpha=0.1. We will also assess individual study and subgroup characteristics and
      perform a sensitivity analysis. Publication bias will be assessed using funnel
      plot and statistical analysis of Egger's test. ETHICS AND DISSEMINATION: Ethics
      approval is not required because the work will be carried out on published
      documents. The authors will publish findings from this review through peer
      reviewed publication or conference presentations. PROSPERO REGISTRATION NUMBER:
      CRD42017067179.

PMID- 30232106
TI  - Geographical and socioeconomic differences in uptake of Pap test and mammography
      in Italy: results from the National Health Interview Survey.
AB  - OBJECTIVE: The Italian National Health Service instituted cervical and breast
      cancer screening programmes in 1999; the local health authorities have a mandate
      to implement these screening programmes by inviting all women aged 25-64 years
      for a Pap test every 3 years (or for an Human Papilloma Virus (HPV) test every 5
      years) and women aged 50-69 years for a mammography every 2 years. However, the
      implementation of screening programmes throughout the country is still
      incomplete. This study aims to: (1) describe cervical and breast cancer screening
      uptake and (2) evaluate geographical and individual socioeconomic difference in
      screening uptake. METHODS: Data both from the Italian National Health Interview
      Survey (NHIS) conducted by the National Institute of Statistics in 2012-2013 and
      from the Italian National Centre for Screening Monitoring (INCSM) were used. The
      NHIS interviewed a national representative random sample of 32 831 women aged 25
      64 years and of 16 459 women aged 50-69 years. Logistic multilevel models were
      used to estimate the effect of socioeconomic variables and behavioural factors
      (level 1) on screening uptake. Data on screening invitation coverage at the
      regional level, taken from INCSM, were used as ecological (level 2) covariates.
      RESULTS: Total 3-year Pap test and 2-year mammography uptake were 62.1% and
      56.4%, respectively; screening programmes accounted for 1/3 and 1/2 of total test
      uptake, respectively. Strong geographical differences were observed. Uptake was
      associated with high educational levels, healthy behaviours, being a former
      smoker and being Italian versus foreign national. Differences in uptake between
      Italian regions were mostly explained by the invitation coverage to screening
      programmes. CONCLUSIONS: The uptake of both screening programmes in Italy is
      still under acceptable levels. Screening programme implementation has the
      potential to reduce the health inequalities gap between regions but only if
      uptake increases.

PMID- 30232107
TI  - Associations between understanding of current treatment intent, communication
      with healthcare providers, preferences for invasive life-sustaining interventions
      and decisional conflict: results from a survey of patients with advanced heart
      failure in Singapore.
AB  - OBJECTIVES: To make informed choices about use of future invasive life-sustaining
      interventions (ILSI), patients with congestive heart failure (CHF) need to
      correctly understand the intent of their current treatments. However, healthcare
      providers may be wary of having these discussions due to fear of distressing
      patients. In this study, we assessed whether patients who understand their
      treatment intent are less willing to undergo ILSI and are indeed more
      psychologically distressed. DESIGN, PARTICIPANTS AND OUTCOMES: As part of a cross
      sectional survey conducted prior to randomising patients for a trial, we asked
      282 patients with advanced CHF (New York Heart Association Class III and IV)
      whether they believe their existing treatments would cure their heart condition,
      their willingness to undergo ILSI and assessed their anxiety and depression using
      the Hospital Anxiety and Depression Scale. RESULTS: Approximately half of
      patients reported a willingness to undergo ILSI if needed. Only 22% knew that
      their current treatments were not curative. These patients were far less willing
      to undergo ILSI (OR 0.28, 95% CI 0.15 to 0.56) and were not at a greater risk of
      having clinically significant anxiety (OR 0.72, 0.34 to 1.54) and depression (OR
      0.70, 0.33 to 1.47) compared with those who did not understand their current
      treatment intent. CONCLUSIONS: Improving patients' understanding of the intent of
      their current treatments can help patients make informed choices about ILSI.
      TRIAL REGISTRATION NUMBER: NCT02299180; Pre-results.

PMID- 30232108
TI  - Telehealth for patients with chronic obstructive pulmonary disease (COPD): a
      systematic review and meta-analysis protocol.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a highly prevalent
      chronic disease characterised by persistent respiratory symptoms. A focus of COPD
      interventional studies is directed towards prevention of exacerbations leading to
      hospital readmissions. Telehealth as a method of remote patient monitoring and
      care delivery may be implemented to reduce hospital readmissions and improve self
      management of disease. Prior reviews have not systematically assessed the
      efficacies of various telehealth functionalities in patients with COPD at
      different stages of disease severity. We aim to evaluate which COPD telehealth
      interventions, classified by their functionalities, are most effective in
      improving patient with COPD management measured by both clinical and resource
      utilisation outcomes. METHODS AND ANALYSIS: We will conduct a systematic review
      which will include randomised controlled trials comparing the efficacy of
      telehealth interventions versus standard care in patients with COPD with
      confirmed disease severity based on forced expiratory volume(%) levels. An
      electronic search strategy will be used to identify trials published since 2000
      in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINHAL.
      Telehealth is described as remote monitoring and delivery of care where patient
      data/clinical information is routinely or continuously collected and/or
      processed, presented to the patient and transferred to a clinical care
      institution for feedback, triage and intervention by a clinical specialist. Two
      authors will independently screen articles for inclusion, assess risk of bias and
      extract data. We will merge studies into a meta-analysis if the interventions,
      technologies, participants and underlying clinical questions are homogeneous
      enough. We will use a random-effects model, as we expect some heterogeneity
      between interventions. In cases where a meta-analysis is not possible, we will
      synthesise findings narratively. We will assess the quality of the evidence for
      the main outcomes using GRADE. ETHICS AND DISSEMINATION: Research ethics approval
      is not required. The findings will be disseminated through publication in a peer
      reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018083671.

PMID- 30232110
TI  - Examining protective and buffering associations between sociocultural factors and
      adverse childhood experiences among American Indian adults with type 2 diabetes:
      a quantitative, community-based participatory research approach.
AB  - OBJECTIVES: The purpose of this study was to determine the frequency of select
      adverse childhood experiences (ACEs) among a sample of American Indian (AI)
      adults living with type 2 diabetes (T2D) and the associations between ACEs and
      self-rated physical and mental health. We also examined associations between
      sociocultural factors and health, including possible buffering processes. DESIGN:
      Survey data for this observational study were collected using computer-assisted
      survey interviewing techniques between 2013 and 2015. SETTING: Participants were
      randomly selected from AI tribal clinic facilities on five reservations in the
      upper Midwestern USA. PARTICIPANTS: Inclusion criteria were a diagnosis of T2D,
      age 18 years or older and self-identified as AI. The sample includes n=192 adults
      (55.7% female; mean age=46.3 years). PRIMARY MEASURES: We assessed nine ACEs
      related to household dysfunction and child maltreatment. Independent variables
      included social support, diabetes support and two cultural factors: spiritual
      activities and connectedness. Primary outcomes were self-rated physical and
      mental health. RESULTS: An average of 3.05 ACEs were reported by participants and
      81.9% (n=149) said they had experienced at least one ACE. Controlling for gender,
      age and income, ACEs were negatively associated with self-rated physical and
      mental health (p<0.05). Connectedness and social support were positively and
      significantly associated with physical and mental health. Involvement in
      spiritual activities was positively associated with mental health and diabetes
      specific support was positively associated with physical health. Social support
      and diabetes-specific social support moderated associations between ACEs and
      physical health. CONCLUSIONS: This research demonstrates inverse associations
      between ACEs and well-being of adult AI patients with diabetes. The findings
      further demonstrate the promise of social and cultural integration as a critical
      component of wellness, a point of relevance for all cultures. Health
      professionals can use findings from this study to augment their assessment of
      patients and guide them to health-promoting social support services and resources
      for cultural involvement.

PMID- 30232111
TI  - Partners at Care Transitions: exploring healthcare professionals' perspectives of
      excellence at care transitions for older people.
AB  - INTRODUCTION: Hospital admissions are shorter than they were 10 years ago.
      Notwithstanding the benefits of this, patients often leave hospital requiring
      ongoing care. The transition period can therefore be risky, particularly for
      older people with complex health and social care needs. Previous research has
      predominantly focused on the errors and harms that occur during transitions of
      care. In contrast, this study adopts an asset-based approach to learn from
      factors that facilitate safe outcomes. It seeks to explore how staff within high
      performing ('positively deviant') teams successfully support transitions from
      hospital to home for older people. METHODS AND ANALYSIS: Six high-performing
      general practices and six hospital specialties that demonstrate exceptionally low
      or reducing 30-day emergency hospital readmission rates will be invited to
      participate in the study. Healthcare staff from these clinical teams will be
      recruited to take part in focus groups, individual interviews and/or observations
      of staff meetings. Data collection will explore the ways in which teams
      successfully deliver exceptionally safe transitional care and how they overcome
      the challenges faced in their everyday clinical work. Data will be thematically
      analysed using a pen portrait approach to identify the manifest (explicit) and
      latent (abstract) factors that facilitate success. ETHICS AND DISSEMINATION:
      Ethical approval was obtained from the University of Leeds. The study will help
      develop our understanding of how multidisciplinary staff within different
      healthcare settings successfully support care transitions for older people.
      Findings will be disseminated to academic and clinical audiences through peer
      reviewed articles, conferences and workshops. Findings will also inform the
      development of an intervention to improve the safety and experience of older
      people during transitions from hospital to home.

PMID- 30232109
TI  - Cross-sectional analysis of sleep-promoting and wake-promoting drug use on
      health, fatigue-related error, and near-crashes in police officers.
AB  - OBJECTIVES: To examine sleep-promoting and wake-promoting drug use in police
      officers and associations between their use and health (excessive sleepiness,
      stress and burnout), performance (fatigue-related errors) and safety (near
      crashes) outcomes, both alone and in combination with night-shift work. DESIGN:
      Cross-sectional survey. SETTING: Police officers from North America completed the
      survey either online or via paper/pencil at a police station. PARTICIPANTS: 4957
      police participated, 3693 online (91.9%, participation rate) and 1264 onsite
      (cooperation rate 63.1%). MAIN OUTCOME MEASURES: Sleep-promoting and wake
      promoting drug use, excessive sleepiness, near-crash motor vehicle crashes,
      dozing while driving, fatigue errors, stress and burnout. RESULTS: Over the past
      month, 20% of police officers reported using sleep-promoting drugs and drugs
      causing sleepiness, while wake-promoting agents were used by 28% of police (5%
      used wake-promoting drugs, 23% used high levels of caffeine and 4% smoked to stay
      awake). Use of sleep-promoting drugs was associated with increased near-crashes
      (OR=1.61; 95% CI 1.21 to 2.13), fatigue-related errors (OR=1.75; 95% CI 1.32 to
      2.79), higher stress (OR=1.41; 95% CI 1.10 to 1.82), and higher burnout (OR=1.83;
      95% CI 1.40 to 2.38). Wake-promoting drug use, high caffeine and smoking to stay
      awake were associated with increased odds of a fatigue-related error, stress and
      burnout (ORs ranging from 1.68 to 2.56). Caffeine consumption was common, and
      while smoking was not, of those participants who did smoke, one-in-three did so
      to remain awake. Night-shift work was associated with independent increases in
      excessive sleepiness, near-crashes and fatigue-related errors. Interactions
      between night-shift work and wake-promoting drug use were also found for
      excessive sleepiness. CONCLUSIONS: Police who use sleep-promoting and wake
      promoting drugs, especially when working night shifts, are most vulnerable to
      adverse health, performance and safety outcomes. Future research should examine
      temporal relationships between shift work, drug use and adverse outcomes, in
      order to develop optimal alertness management strategies.

PMID- 30232112
TI  - The UALE project: a cross-sectional approach for trends in HIV/STI prevalence
      among key populations attending STI clinics in Guatemala.
AB  - OBJECTIVE: To describe and compare trends in prevalence, sexual behaviour and HIV
      transmission knowledge data related to sexually transmitted infections (STI) and
      HIV in patients attending three STI clinics over an 8-year period in Escuintla
      Department, Guatemala. METHODS: STI clinic attendees were classified into
      transmission groups as follows: female sex workers (FSW), men who have sex with
      men (MSM) and 'high-risk heterosexuals' (HRH). Annual cross-sectional analysis
      and multivariable Poisson regression adjusted for sociodemographic variables were
      used for prevalence comparisons and adjusted prevalence trends for HIV/STI
      outcomes and used for adjusted trends in proportions in sexual behaviour and HIV
      transmission knowledge outcomes. Endocervical swabs were obtained to detect
      trichomonas, chlamydia and neisseria infections. Serologies for syphilis and HIV
      were performed using rapid tests. For reactive HIV samples, positivity was
      confirmed by an ELISA. All reactive syphilis samples were further confirmed for
      diagnosis of active syphilis disease. RESULTS: From a total of 4027 clinic
      attendees, 3213 (79.78%) were FSW, 229 (5.69%) were MSM and 585 (14.53%) were
      HRH. The proportion of FSW, MSM and HRH who had a single visit was 56.42%, 57.23%
      and 91.10%, respectively. Overall, HIV prevalence was 2.10% in FSW, 8.17% in MSM
      and 4.12% in HRH. Prevalence trends in HIV and syphilis decreased in FSW.
      Prevalence trends in gonorrhoea did not decrease over time neither in FSW nor in
      HRH. Chlamydia and trichomonas infections in HRH showed an increase prevalence
      trend. In FSW, trends in condom use in last sexual intercourse with regular and
      occasional clients were above 93%. CONCLUSIONS: FSW show a decreasing trend in
      HIV, syphilis and chlamydia prevalence. Gonorrhoea prevalence in FSW and HRH did
      not decrease over time. HRH is a hard to engage population with low follow-up
      rates and high potential to act as a bridge population.

PMID- 30232113
TI  - Comparison of high flow nasal cannula oxygen and conventional oxygen therapy on
      ventilatory support duration during acute-on-chronic respiratory failure: study
      protocol of a multicentre, randomised, controlled trial. The 'HIGH-FLOW ACRF'
      study.
AB  - INTRODUCTION: This study protocol describes a trial designed to investigate
      whether high-flow heated and humidified nasal oxygen (HFHO) therapy in patients
      with hypercapnic acute respiratory failure (ARF) reduces the need of non-invasive
      ventilation (NIV). METHODS AND ANALYSIS: This is an open-label, superiority,
      international, parallel-group, multicentre randomised controlled two-arm trial,
      with an internal feasibility pilot phase. 242 patients with hypercapnic ARF
      requiring NIV admitted to an intensive care unit, an intermediate care or a
      respiratory care unit will be randomised in a 1:1 ratio to receive HFHO or
      standard oxygen in between NIV sessions. Randomisation will be centralised and
      stratified by centre and pH at admission (pH <=7.25 or >7.25). The primary
      outcome will be the number of ventilator-free days (VFDs) and alive at day 28
      postrandomisation. The secondary outcomes will encompass parameters related to
      the VFDs, comfort and tolerance variables, hospital length of stay and mortality.
      VFDs at 28 days postrandomisation will be compared between the two groups by
      Wilcoxon-Mann-Whitney two-sample rank-sum test in the intention-to-treat
      population. A sensitivity analysis will be conducted in the population of
      patients for whom the criteria of switching from NIV to spontaneous breathing, or
      conversely, are not strictly verified. ETHICS AND DISSEMINATION: The protocol has
      been approved by the Comite de Protection des Personnes (CPP) Sud-Ouest & Outre
      Mer IV (ref CPP17-049a/2017-A01830-53) and will be carried out in accordance with
      the Declaration of Helsinki and Good Clinical Practice guidelines. A trial
      steering committee will oversee the progress of the study. Findings will be
      disseminated through national and international scientific conferences, and
      publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03406572.

PMID- 30232115
TI  - Let's talk numbers: a qualitative study of community-dwelling US adults to
      understand the role of numeracy in the management of heart failure.
AB  - OBJECTIVE: To examine the perspectives of adults with heart failure (HF) about
      numerical concepts integral to HF self-care. SETTING: This qualitative study took
      place at an urban academic primary care practice. PARTICIPANTS: Thirty men and
      women aged 47-89 years with a history of HF were recruited to participate.
      Eligibility criteria included: a history of HF (>=1 year), seen at the clinic
      within the last year, and a HF hospitalisation within the last 6 months. Non
      English speakers and those with severe cognitive impairment were excluded.
      METHODS: In-depth semistructured interviews were conducted. Participants were
      interviewed about numeracy across three domains of HF self-care: (1) monitoring
      weight,(2) maintaining a diet low in salt and (3) monitoring blood pressure.
      Interviews were audio-taped, transcribed verbatim and analysed using grounded
      theory and word cloud techniques. RESULTS: Five key themes reflecting
      participants' attitudes towards numerical concepts pertaining to weight, diet and
      blood pressure were identified: (1) Communication between healthcare providers
      and patients is a complex, multistage process; (2) Patients possess a wide range
      of knowledge and understanding; (3) Social and caregiver support is critical for
      the application of numerical concepts; (4) Prior health experiences shape outlook
      towards numerical concepts and instructions and (5) Fear serves as a barrier and
      a facilitator to carrying out HF self-care tasks that involve numbers. The
      findings informed a theoretical framework of health numeracy in HF. CONCLUSION:
      Effective communication of numerical concepts which pertain to HF self-care is
      highly variable. Many patients with HF lack basic understanding and numeracy
      skills required for adequate self-care. As such, patients rely on caregivers who
      may lack HF training. HF-specific training of caregivers and research that seeks
      to elucidate the intricacies of the patient-caregiver relationship in the context
      of health numeracy and HF self-care are warranted.

PMID- 30232116
TI  - Classic e-Delphi survey to provide national consensus and establish priorities
      with regards to the factors that promote the implementation and continued
      development of non-medical prescribing within health services in Wales.
AB  - OBJECTIVE: To provide national consensus and establish priorities with regards to
      the factors that promote the implementation and continued development of non
      medical prescribing within health services. DESIGN: Classic e-Delphi survey.
      SETTING: National study in Wales. PARTICIPANTS: Pharmacists, nurses and allied
      health professionals with the independent/supplementary prescribing
      qualification. RESULTS: A total of 55 non-medical prescribers agreed to become
      members of the expert panel of whom 42 (76%) completed the round 1 questionnaire,
      40/42 (95%) completed round 2 and 34/40 (85%) responded to round 3. Twenty-one
      statements were developed, and consensus was achieved on nine factors
      representing those necessary for the successful implementation of non-medical
      prescribing and five representing actions required for its continued development.
      Strategic fit between non-medical prescribing and existing service provision,
      organisation preparedness, visible benefits, good managerial and team support,
      and a clear differentiation of roles were each important influences. CONCLUSION:
      Given the high degree of consensus, this list of factors and actions should
      provide guidance to managers and commissioners of services wishing to initiate or
      extend non-medical prescribing. This information should be considered
      internationally by other countries outside of the UK wishing to implement
      prescribing by non-medical healthcare professionals.

PMID- 30232118
TI  - Prostitution is a symptom of structural inequalities.

PMID- 30232114
TI  - Neurophysiological correlates of motor planning and movement initiation in ACL
      reconstructed individuals: a case-control study.
AB  - INTRODUCTION: Current evidence suggests that the loss of mechanoreceptors after
      anterior cruciate ligament (ACL) tears might be compensated by increased cortical
      motor planning. This occupation of cerebral resources may limit the potential to
      quickly adapt movements to unforeseen external stimuli in the athletic
      environment. To date, studies investigating such neural alterations during
      movement focused on simple, anticipated tasks with low ecological validity. This
      trial, therefore, aims to investigate the cortical and biomechanical processes
      associated with more sport-related and injury-related movements in ACL
      reconstructed individuals. METHODS AND ANALYSIS: ACL-reconstructed participants
      and uninjured controls will perform repetitive countermovement jumps with single
      leg landings. Two different conditions are to be completed: anticipated (n=35)
      versus unanticipated (n=35) successful landings. Under the anticipated condition,
      participants receive the visual information depicting the requested landing leg
      prior to the jump. In the unanticipated condition, this information will be
      provided only about 400 msec prior to landing. Neural correlates of motor
      planning will be measured using electroencephalography. In detail, movement
      related cortical potentials, frequency spectral power and functional connectivity
      will be assessed. Biomechanical landing quality will be captured via a capacitive
      force plate. Calculated parameters encompass time to stabilisation, vertical peak
      ground reaction force, and centre of pressure path length. Potential systematic
      differences between ACL-reconstructed individuals and controls will be identified
      in dependence of jumping condition (anticipated/ unanticipated, injured/uninjured
      leg and controls) by using interference statistics. Potential associations
      between the cortical and biomechanical measures will be calculated by means of
      correlation analysis. In case of statistical significance (alpha<0.05.) further
      confounders (cofactors) will be considered. ETHICS AND DISSEMINATION: The
      independent Ethics Committee of the University of Frankfurt (Faculty of
      Psychology and Sports Sciences) approved the study. Publications in peer-reviewed
      journals are planned. The findings will be presented at scientific conferences.
      TRIAL STATUS: At the time of submission of this manuscript, recruitment is
      ongoing. TRIAL REGISTRATION NUMBER: NCT03336060; Pre-results.

PMID- 30232119
TI  - Dietary gluten and type 1 diabetes.

PMID- 30232120
TI  - Dartmouth College professor resigns after plagiarism finding.

PMID- 30232117
TI  - 'Mind your Moles' study: protocol of a prospective cohort study of melanocytic
      naevi.
AB  - INTRODUCTION: Having many melanocytic naevi or 'moles' on the skin is the
      strongest predictor of melanoma; thus, much can be learnt from investigating
      naevi in the general population. We aim to improve the understanding of the
      epidemiology and biology of naevi by conducting a 3-year prospective study of
      melanocytic naevi in adults. METHODS AND ANALYSIS: This is a population-based
      cohort study of melanocytic naevi in 200 adults aged 20-69 years recruited via
      the Australian electoral roll. At baseline, participants will complete a
      questionnaire on their sun behaviour and health and undergo a clinical
      examination. Three-dimensional (3D) total-body photography will be used to record
      the images of skin lesions. Pigmented naevi will be analysed in terms of number,
      diameter, colour and border irregularity using automated analysis software
      (excluding scalp, beneath underwear and soles of feet). All naevi >=5 mm will be
      recorded using the integrated dermoscopy photographic system. A saliva sample
      will be obtained at baseline for genomic DNA analysis of pigmentation, naevus and
      melanoma-associated genes using the Illumina HumanCoreExome platform. The sun
      behaviour and health follow-up questionnaire, clinical examination and 3D total
      body photography will be repeated every 6 months for 3 years. The first 50
      participants will also undergo manual counts of naevi >=2 mm and >=5 mm at
      baseline, 6-month and 12-month follow-ups. Microbiopsy and excision of naevi of
      research interest is planned to commence at the 18-month time point among those
      who agree to donate samples for detailed histopathological and molecular
      assessment. ETHICS AND DISSEMINATION: This study was approved by the Metro South
      Health Human Research Ethics Committee in April 2016 (approval number:
      HREC/16/QPAH/125). The findings will be disseminated through peer-reviewed and
      non-peer-reviewed publications and presentations at conferences.

PMID- 30232121
TI  - Description of digital fluoroscopic excretory urography in healthy New Zealand
      rabbits (Oryctolagus cuniculus).
AB  - Disorders of the kidneys and urinary tract are relatively common in rabbits.
      Survey radiographs and abdominal ultrasound have inherent limitations in the
      evaluation of the urinary tract in this species; because of that, contrast study
      modalities are a valuable diagnostic tool in rabbits with urinary disorders. The
      aims of this study were to describe digital fluoroscopic excretory urography
      (DFEU) and to determine the urogram phases in healthy New Zealand rabbits. The
      median time of beginning of the nephrographic and pyelographic phases was 10
      seconds (IQR: 10-12 seconds) and 1.39 minutes (IQR: 1.27-1.60 minutes). The
      median time in which the contrast medium was visible in the urinary bladder was
      1.58 minutes (IQR: 1.44-1.72 minutes). Results of this study indicate that DFEU
      provides a good degree of opacification of the kidneys as well as the ureters,
      and allows the evaluation of the urogram phases. Text not justifed in the proof
      version.

PMID- 30232122
TI  - GMC is told to use restraint in appealing against tribunal findings.

PMID- 30232095
TI  - International Union of Basic and Clinical Pharmacology. CV. Somatostatin
      Receptors: Structure, Function, Ligands, and New Nomenclature.
AB  - Somatostatin, also known as somatotropin-release inhibitory factor, is a
      cyclopeptide that exerts potent inhibitory actions on hormone secretion and
      neuronal excitability. Its physiologic functions are mediated by five G protein
      coupled receptors (GPCRs) called somatostatin receptor (SST)1-5. These five
      receptors share common structural features and signaling mechanisms but differ in
      their cellular and subcellular localization and mode of regulation. SST2 and SST5
      receptors have evolved as primary targets for pharmacological treatment of
      pituitary adenomas and neuroendocrine tumors. In addition, SST2 is a prototypical
      GPCR for the development of peptide-based radiopharmaceuticals for diagnostic and
      therapeutic interventions. This review article summarizes findings published in
      the last 25 years on the physiology, pharmacology, and clinical applications
      related to SSTs. We also discuss potential future developments and propose a new
      nomenclature.

PMID- 30232123
TI  - Moral reasons not to breastfeed: a response to Woollard and Porter.
AB  - Woollard and Porter argue that mothers have no moral duty to breastfeed their
      babies. Rather, mothers simply have moral reason(s) to breastfeed, stemming from
      the benefits of breast feeding for babies. According to Woollard and Porter,
      doing what one has moral reason to do is often supererogatory, not obligatory. I
      agree that mothers have no moral duty to breastfeed. However, it is misleading to
      suggest that mothers in general have moral reason to breastfeed and to liken not
      breastfeeding to not performing some supererogatory action. I will suggest
      mothers in general have pro tanto, but not all-things-considered, moral reason to
      breastfeed. Moreover, I suggest many mothers also have pro tanto moral reasons
      not to breastfeed. Breastfeeding is not always supererogatory; indeed, sometimes
      not breastfeeding is morally better. This is important because it contradicts
      dangerous assumptions in public discourse. One way of characterising popular
      consensus about breastfeeding is as Woollard and Porter do: mothers have a duty
      to breastfeed. But we might also characterise popular consensus differently: all
      moral reasons for/against breastfeeding are on the 'pro' breastfeeding side of
      the issue, whereas if there are any (good) reasons not to breastfeed these are
      non-moral (prudential). Woollard and Porter's argument is important and correct
      in concluding that mothers have no duty to breastfeed, but it leaves this other
      false and dangerous idea intact and even subtly reinforces it.

PMID- 30232124
TI  - Doctor who charged for locum work while employed to do research job is suspended
      for 12 months.

PMID- 30232125
TI  - A New Tool to Reveal Bacterial Signaling Mechanisms in Antibiotic Treatment and
      Resistance.
AB  - The rapid emergence of antimicrobial resistance is a major threat to human
      health. Antibiotics modulate a wide range of biological processes in bacteria and
      as such, the study of bacterial cellular signaling could aid the development of
      urgently needed new antibiotic agents. Due to the advances in bacterial
      phosphoproteomics, such a systemwide analysis of bacterial signaling in response
      to antibiotics has recently become feasible. Here we present a dynamic view of
      differential protein phosphorylation upon antibiotic treatment and antibiotic
      resistance. Most strikingly, differential phosphorylation was observed on highly
      conserved residues of resistance regulating transcription factors, implying a
      previously unanticipated role of phosphorylation mediated regulation. Using the
      comprehensive phosphoproteomics data presented here as a resource, future
      research can now focus on deciphering the precise signaling mechanisms
      contributing to resistance, eventually leading to alternative strategies to
      combat antimicrobial resistance.

PMID- 30232126
TI  - Donor-derived MDS/AML in families with germline GATA2 mutation.

PMID- 30232127
TI  - Quantitation of Integrated HIV Provirus by Pulsed-Field Gel Electrophoresis and
      Droplet Digital PCR.
AB  - We utilized pulsed-field gel electrophoresis (PFGE) to purify high-molecular
      weight DNA from HIV-infected cells. This purification, in combination with our
      previously described droplet digital PCR (ddPCR) assay, was used to develop a
      method to quantify proviral integrated HIV DNA free of lower-molecular-weight
      species of HIV DNA. Episomal 2-long-terminal-repeat (2-LTR) circles were
      completely cleared from HIV DNA samples. Technical replicates of the complete
      assay, starting with the same specimens, resulted in no statistical differences
      in quantification of integrated HIV gag sequences in cellular DNA from cells from
      HIV-infected subjects after prolonged treatment with antiretroviral therapy
      (ART). The PFGE ddPCR assay was compared to the Alu-gag quantitative PCR (qPCR)
      assay, the most widely used assay to measure proviral integrated HIV DNA.
      Spearman's rho nonparametric correlation determined PFGE ddPCR results to be
      positively correlated with Alu-gag qPCR results (r = 0.7052; P = 0.0273). In
      summary, PFGE ddPCR is a sensitive, reproducible, and robust method to measure
      proviral integrated HIV DNA and is theoretically more accurate than previously
      described assays, because it is a direct measure of integrated HIV DNA.

PMID- 30232128
TI  - Atypical Bacterial Growth within Units of Platelets Challenges Transfusion
      Medicine Dogma.
AB  - Although transfusion-transmitted bacterial infection is relatively rare,
      mitigation of bacterial contamination of platelet units is arguably the top
      current transfusion-related safety concern. Several different technologies have
      been employed to detect or neutralize bacteria in platelet concentrates. However,
      studies of the efficacy of these systems have been hampered by problematic
      definitions of what represents a "true-positive" versus a "false-positive"
      culture result. In the current issue of the Journal of Clinical Microbiology (M.
      Cloutier, M.-E. Nolin, H. Daoud, A. Jacques, M. J. de Grandmont, E Ducas, G.
      Delage, and L. Thibault, J Clin Microbiol 56:e01105-18, 2018,
      https://doi.org/10.1128/JCM.01105-18), it was demonstrated that the growth of
      Bordetella holmesii is inhibited by the platelet storage environment, which may
      explain why the results of initial positive platelet cultures are not always
      confirmed by subsequent cultures later during the storage period. This important
      finding is at odds with the generally held belief within the field of transfusion
      medicine that initially positive platelet cultures that are not confirmed on
      repeat testing are instrumentation-based false positives. The clinical risk
      profile of organisms demonstrating storage-related low viability is worthy of
      further study.

PMID- 30232129
TI  - Evaluation of Risk Factors for Clostridium difficile Infection Based on
      Immunochromatography Testing and Toxigenic Culture Assay.
AB  - In recent years, the diagnostic method of choice for Clostridium difficile
      infection (CDI) is a rapid enzyme immunoassay in which glutamate dehydrogenase
      (GDH) antigen and C. difficile toxin can be detected (C. diff Quik Chek Complete;
      Alere Inc.) (Quik Chek). However, the clinical significance remains unclear in
      cases that demonstrate a positive result for GDH antigen and are negative for
      toxin. In this study, we used the Quik Chek test kit on fecal samples, with an
      additional toxin detection step using a toxigenic culture assay for the
      aforementioned cases. CDI risk factors were assessed among the 3 groups divided
      by the Quik Chek test results. The study involved 1,565 fecal samples from
      patients suspected to have CDI who were hospitalized during the period of April
      2012 to March 2014. The 3 groups were defined as follows: both GDH antigen
      positive and toxin positive (by Quik Chek test) (toxin-positive [TP] group, n =
      109), both GDH antigen and toxin negative (toxin-negative [TN] group, n = 111),
      and positive only for GDH antigen but toxin positive with subsequent toxigenic
      culture (toxigenic culture [TC] group, n = 72). The gender, age, number of
      hospitalization days, white blood cell (WBC) counts, serum albumin levels, body
      mass index (BMI), fecal consistency, and use of antibacterials and proton pump
      inhibiters (PPIs) were analyzed. The positive rate for the fecal direct Quik Chek
      test was 7.0% (109/1,565 cases). However, toxigenic culture assays using the Quik
      Chek test for only the GDH-antigen-positive/toxin-negative samples were 35.3%
      positive (72/204 cases). As a result, the true positive rate for C. difficile
      toxin detection was estimated to be 11.6% (181/1,565 cases). Moreover,
      significant differences (P < 0.05) in the number of hospitalization days (>50
      days), WBC counts (>10,000 WBCs/MUl), and use of PPIs comparing the TN, TP, and
      TC groups, were observed. The odds ratios (ORs) for the development of CDI were
      1.61 (95% confidence interval [CI], 0.94 to 2.74) and 2.98 (95% CI, 1.59 to 5.58)
      for numbers of hospitalization days, 2.16 (95% CI, 1.24 to 3.75) and 2.24 (95%
      CI, 1.21 to 4.14) for WBC counts, and 9.03 (95% CI, 4.9 to 16.6) and 9.15 (95%
      CI, 4.59 to 18.2) for use of PPIs in the TP and TC groups, respectively. These
      findings demonstrated that the use of PPIs was a significant risk factor for CDI
      development. Moreover, antibacterials such as carbapenems, cephalosporins, and
      fluoroquinolones were demonstrated to be risk factors. In conclusion,
      identification of the TC group of patients is thought to be important, as this
      study demonstrates that this group bears the same high risk of developing CDI as
      the TP group.

PMID- 30232130
TI  - Direct Detection of Emergent Fungal Pathogen Candida auris in Clinical Skin Swabs
      by SYBR Green-Based Quantitative PCR Assay.
AB  - The recent emergence of the multidrug-resistant and pathogenic yeast Candida
      auris continues to cause public health concern worldwide. C. auris is alarming
      because it causes health care-associated outbreaks and can establish invasive
      infections with high mortality rates. Transmission between patients is
      facilitated by the ability of C. auris to persistently colonize multiple body
      sites, including the skin, and survive for weeks on surfaces in health care
      settings. Rapid identification of colonized patients is needed to implement
      timely infection control measures. Currently, CDC laboratories use an enrichment
      culture-based approach that can take up to 2 weeks to identify C. auris from
      composite swabs from the bilateral axillae and groin. A rapid SYBR green
      quantitative PCR (qPCR) assay that can identify C. auris in a single day was
      recently described. In this study, we developed the SYBR green qPCR assay further
      by incorporating a DNA extraction procedure for skin swabs and by including an
      internal amplification control based on the distinguishable melt curve of a
      lambda DNA amplicon. The assay was conducted using 103 clinical axilla/groin skin
      swab samples. Using the enrichment culture-based approach as a gold standard, we
      determined that the SYBR green C. auris qPCR has a sensitivity of 0.93 and
      specificity of 0.96. Overall, we found that the SYBR green C. auris qPCR assay
      can be successfully applied for rapid and accurate detection of C. auris in
      patient skin swabs, thereby increasing diagnostic options for this emerging
      pathogen.

PMID- 30232131
TI  - Performance of Commercially Available Serological Screening Tests for Human T
      Cell Lymphotropic Virus Infection in Brazil.
AB  - Serological screening for human T-cell lymphotropic virus type 1 (HTLV-1) is
      usually performed using enzyme-linked immunosorbent assay (ELISA), particle
      agglutination, or chemiluminescence assay kits. Due to an antigen matrix
      improvement entailing the use of new HTLV antigens and changes in the format of
      HTLV screening tests, as well as newly introduced chemiluminescence assays
      (CLIAs), a systematic evaluation of the accuracy of currently available
      commercial tests is warranted. We aimed to assess the performance of commercially
      available screening tests for HTLV infection diagnosis. A diagnostic accuracy
      study was conducted on a panel of 397 plasma samples: 200 HTLV-negative plasma
      samples, 170 HTLV-positive plasma samples, and 27 plasma samples indeterminate by
      Western blotting (WB). WB-indeterminate samples (i.e., those yielding no specific
      bands for HTLV-1 and/or HTLV-2) were assessed by PCR, and the results were used
      to compare agreement among the commercially available ELISA screening tests. For
      performance analysis, WB-indeterminate samples were excluded, resulting in a
      final study panel of 370 samples. Three ELISA kits (Murex HTLV-1/2 [Murex], anti
      HTLV-1/2 SYM Solution [SYM Solution], and Gold ELISA HTLV-1/2 [Gold ELISA]) and
      one CLIA kit (Architect rHTLV-1/2) were evaluated. All screening tests
      demonstrated 100% sensitivity. Concerning the HTLV-negative samples, the SYM
      Solution and Gold ELISA kits had specificity values of >99.5%, while the
      Architect rHTLV-1/2 test presented 98.1% specificity, followed by Murex, which
      had a specificity of 92.0%. Regarding the 27 samples with WB-indeterminate
      results, after PCR confirmation, all ELISA kits showed 100% sensitivity but low
      specificity. Accuracy findings were corroborated by the use of Cohen's kappa
      value, which evidenced slight and fair agreement between PCR analysis and ELISAs
      for HTLV infection diagnosis. Based on the data, we believe that all evaluated
      tests can be safely used for HTLV infection screening.

PMID- 30232132
TI  - Specificity of QuantiFERON-TB Plus, a New-Generation Interferon Gamma Release
      Assay.
AB  - Interferon gamma release assays (IGRAs) are important tools in identifying prior
      tuberculosis exposure. The new-generation QuantiFERON-TB Gold Plus (QFT-Plus)
      assay, recently approved for use in the United States, differs from the current
      generation QFT Gold-In-Tube (QFT-GIT) assay with the addition of a second antigen
      tube that also contains novel CD8+ T-cell-stimulating peptides. The QFT-Plus
      assay has increased sensitivity in immunocompromised populations, and we sought
      to assess the specificity of QFT-Plus compared to that of QFT-GIT in low-risk
      individuals. We enrolled adults without tuberculosis risk factors, including a
      subgroup with pulmonary nontuberculous mycobacterial (NTM) disease due to
      Mycobacterium avium complex (MAC) or Mycobacterium abscessus. The primary outcome
      measures included specificity, interassay concordance, and agreement between the
      QFT-Plus and QFT-GIT assays. Of 262 participants enrolled, 51 had pulmonary NTM.
      The median age was 39 years (age range, 18 to 78 years); 73% were female. Among
      the 262 individuals who were enrolled, 5 (1.9%) individuals had positive QFT-Plus
      results, and 3 of these individuals also had positive QFT-GIT results. The two
      individuals with discordant results (QFT-Plus positive/QFT-GIT negative) had only
      one tube positive in the QFT-Plus assay. The overall specificity of QFT-Plus and
      QFT-GIT was 98.1% (95% confidence interval [CI], 95.6, 99.4%) and 98.9% (95% CI,
      96.7, 99.8%), respectively. The QFT-Plus specificity was similar in both the NTM
      (98.0% [95% CI, 89.4, 99.9%]) and non-NTM (98.1% [95% CI, 95.2, 99.5%]) groups.
      QFT-Plus has a high specificity, similar to that of the QFT-GIT assay, including
      in patients with pulmonary MAC or M. abscessus disease.

PMID- 30232133
TI  - Detection of Viruses in Clinical Samples by Use of Metagenomic Sequencing and
      Targeted Sequence Capture.
AB  - Metagenomic shotgun sequencing (MSS) is a revolutionary approach to viral
      diagnostic testing that allows simultaneous detection of a broad range of
      viruses, detailed taxonomic assignment, and detection of mutations associated
      with antiviral drug resistance. To enhance sensitivity for virus detection, we
      previously developed ViroCap, a targeted sequence capture panel designed to
      enrich nucleic acid from a comprehensive set of eukaryotic viruses prior to
      sequencing. To demonstrate the utility of MSS with targeted sequence capture for
      detecting clinically important viruses and characterizing clinically important
      viral features, we used ViroCap to analyze clinical samples from a diagnostic
      virology laboratory containing a broad range of medically relevant viruses. From
      26 samples, MSS with ViroCap detected all of the expected viruses and 30
      additional viruses. Comparing sequencing after capture enrichment with standard
      MSS, we detected 13 viruses only with capture enrichment and observed a
      consistent increase in the number and percentage of viral sequence reads as well
      as the breadth and depth of coverage of the viral genomes. Compared with clinical
      testing, MSS enhanced taxonomic assignment for 15 viruses, and codons associated
      with antiviral drug resistance in influenza A virus, herpes simplex virus (HSV),
      human immunodeficiency virus (HIV), and hepatitis C virus (HCV) could be
      analyzed. Overall, in clinical samples, MSS with targeted sequence capture
      provides enhanced virus detection and information of clinical and epidemiologic
      relevance compared with clinical testing and MSS without targeted sequence
      capture.

PMID- 30232135
TI  - Inching toward a Greater Understanding of Genetic Hypercalciuria: The Role of
      Claudins.

PMID- 30232134
TI  - Claudin-14 Gene Polymorphisms and Urine Calcium Excretion.
AB  - BACKGROUND AND OBJECTIVES: Claudin-16 and -19 are proteins forming pores for the
      paracellular reabsorption of divalent cations in the ascending limb of Henle
      loop; conversely, claudin-14 decreases ion permeability of these pores. Single
      nucleotide polymorphisms in gene coding for claudin-14 were associated with
      kidney stones and calcium excretion. This study aimed to explore the association
      of claudin-14, claudin-16, and claudin-19 single-nucleotide polymorphisms with
      calcium excretion. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a
      retrospective observational study of 393 patients with hypertension who were
      naive to antihypertensive drugs, in whom we measured 24-hour urine calcium
      excretion; history of kidney stones was ascertained by interview; 370 of these
      patients underwent an intravenous 0.9% sodium chloride infusion (2 L in 2 hours)
      to evaluate the response of calcium excretion in three different 2-hour urine
      samples collected before, during, and after saline infusion. Genotypes of claudin
      14, claudin-16, and claudin-19 were obtained from data of a previous genome-wide
      association study in the same patients. RESULTS: Thirty-one single-nucleotide
      polymorphisms of the 3' region of the claudin-14 gene were significantly
      associated with 24-hour calcium excretion and calcium excretion after saline
      infusion. The most significant associated single-nucleotide polymorphism was
      rs219755 (24-hour calcium excretion in GG, 225+/-124 mg/24 hours; 24-hour calcium
      excretion in GA, 194+/-100 mg/24 hours; 24-hour calcium excretion in AA, 124+/-73
      mg/24 hours; P<0.001; calcium excretion during saline infusion in GG, 30+/-21
      mg/2 hours; calcium excretion during saline infusion in GA, 29+/-18 mg/2 hours;
      calcium excretion during saline infusion in AA, 17+/-11 mg/2 hours; P=0.03). No
      significant associations were found among claudin-16 and claudin-19 single
      nucleotide polymorphisms and calcium excretion and between claudin-14, claudin
      16, and claudin-19 single-nucleotide polymorphisms and stones. Bioinformatic
      analysis showed that one single-nucleotide polymorphism at claudin-14 among those
      associated with calcium excretion may potentially influence splicing of
      transcript. CONCLUSIONS: Claudin-14 genotype at the 3' region is associated with
      calcium excretion in 24-hour urine and after the calciuretic stimulus of saline
      infusion.

PMID- 30232136
TI  - CKD in Patients with Bilateral Oophorectomy.
AB  - BACKGROUND AND OBJECTIVES: Premenopausal women who undergo bilateral oophorectomy
      are at a higher risk of morbidity and mortality. Given the potential benefits of
      estrogen on kidney function, we hypothesized that women who undergo bilateral
      oophorectomy are at higher risk of CKD. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We performed a population-based cohort study of 1653 women residing
      in Olmsted County, Minnesota who underwent bilateral oophorectomy before age 50
      years old and before the onset of menopause from 1988 to 2007. These women were
      matched by age (+/-1 year) to 1653 referent women who did not undergo
      oophorectomy. Women were followed over a median of 14 years to assess the
      incidence of CKD. CKD was primarily defined using eGFR (eGFR<60 ml/min per 1.73
      m2 on two occasions >90 days apart). Hazard ratios were derived using Cox
      proportional hazards models, and absolute risk increases were derived using
      Kaplan-Meier curves at 20 years. All analyses were adjusted for 17 chronic
      conditions present at index date, race, education, body mass index, smoking, age,
      and calendar year. RESULTS: Women who underwent bilateral oophorectomy had a
      higher risk of eGFR-based CKD (211 events for oophorectomy and 131 for referent
      women; adjusted hazard ratio, 1.42; 95% confidence interval, 1.14 to 1.77;
      absolute risk increase, 6.6%). The risk was higher in women who underwent
      oophorectomy at age <=45 years old (110 events for oophorectomy and 60 for
      referent women; adjusted hazard ratio, 1.59; 95% confidence interval, 1.15 to
      2.19; absolute risk increase, 7.5%). CONCLUSIONS: Premenopausal women who undergo
      bilateral oophorectomy, particularly those <=45 years old, are at higher risk of
      developing CKD, even after adjusting for multiple chronic conditions and other
      possible confounders present at index date. PODCAST: This article contains a
      podcast at https://www.asn
      online.org/media/podcast/CJASN/2018_10_11_CJASNPodcast_18_1.

PMID- 30232137
TI  - Diversification of Bw4 Specificity and Recognition of a Nonclassical MHC Class I
      Molecule Implicated in Maternal-Fetal Tolerance by Killer Cell Ig-like Receptors
      of the Rhesus Macaque.
AB  - The rhesus macaque is an important animal model for AIDS and other infectious
      diseases; however, studies to address NK cell function in this species have been
      limited by the lack of defined ligands for killer cell Ig-like receptors (KIRs).
      To identify ligands for rhesus macaque KIRs, we adopted a novel approach based on
      a pair of stable cell lines. NFAT-responsive luciferase reporter cell lines
      expressing the extracellular domains of macaque KIRs fused to the transmembrane
      and cytoplasmic domains of CD28 and CD3zeta were incubated with target cells
      expressing individual MHC class I molecules, and ligand recognition was detected
      by the MHC class I-dependent upregulation of luciferase. Using this approach, we
      found that Mamu-KIR3DL01, -KIR3DL06, -KIR3DL08, and -KIR3DSw08 all recognize Mamu
      Bw4 molecules but with differing allotype specificity. In contrast, Mamu-KIR3DL05
      recognizes Mamu-A and Mamu-A-related molecules, including Mamu-A1*002 and -A3*13,
      Mamu-B*036, the product of a recombinant Mamu-B allele with alpha1 and alpha2
      domain sequences derived from a MHC-A gene, and Mamu-AG*01, a nonclassical
      molecule expressed on placental trophoblasts that originated from an ancestral
      duplication of a MHC-A gene. These results reveal an expansion of the lineage II
      KIRs in macaques that recognize Bw4 ligands and identify a nonclassical molecule
      implicated in placental development and pregnancy as a ligand for Mamu-KIR3DL05.
      In addition to offering new insights into KIR-MHC class I coevolution, these
      findings provide an important foundation for investigating the role of NK cells
      in the rhesus macaque as an animal model for infectious diseases and reproductive
      biology.

PMID- 30232139
TI  - How One Might Experimentally Determine if Container Closure Systems and their
      Components and Materials of Construction Contribute Elemental Impurities to
      Packaged Pharmaceutical Drug Products.
AB  - The safety aspects of elemental impurities in finished drug products is a topic
      of considerable importance in the pharmaceutical community and guidelines such as
      ICH Q3D and USP <232> and <233> have been published to provide directions on how
      to assess finished drug products with respect to such impurities. Although a drug
      product's packaging system has been identified as a potential source of elemental
      impurities, comparable guidelines have not been established for assessing
      packaging systems, and their materials and components of construction, with
      respect to their potential to contribute leached elements to packaged drug
      products. In this Commentary, the author considers the critical questions
      associated with selecting materials and components of construction and qualifying
      components and packaging with respect to their potential to add elemental
      impurities to packaged products and suggests means for accomplishing this
      objective.

PMID- 30232140
TI  - A Case Study to Address a Gap in the Device-to-Vial Interface Stopper Push-in by
      Chemo Spikes - An Overlooked Oncology Safety Risk.
AB  - This case study is the first to address the risk, at the device-to-vial
      interface, of a spike pushing a stopper into a vial. It was performed after
      healthcare workers at cancer care hospitals complained about the risk of possible
      exposure to hazardous injectable drugs during the transfer if the spike pushed
      the stopper into the vial. This case study took a three-step approach to
      understand the device-to-vial interface, and the factors that determine stopper
      push-in force threshold and spike puncture force, respectively. The results show
      that the stopper push-in force threshold varies with the spike size, stopper
      properties, and stopper design; while the spike puncture force is determined by
      spike design, spike surface lubricity, stopper properties, and stopper design.
      The case study suggests that, to mitigate the risk of stopper push-in, the spike
      puncture force needs to be significantly lower than the stopper push-in force
      threshold, measured with a flat tip test probe having the same outside diameter
      as typically used spikes. In addition, although some factors which impact stopper
      push-in force threshold also impact spike puncture force in the same trend, such
      as stopper material, other factors which impact stopper push-in force threshold
      do not impact spike puncture force, and vice versa. For example, the spike length
      and cross section area contribute to stopper push-in force threshold but do not
      have significant impact on puncture force. It would be misleading to just compare
      the absolute values of spike puncture forces but neglect the dimensional factors.
      From the stopper and spike compatibility perspective, the case study provides a
      methodology to quantify the risk of stopper being pushed into the vial by the
      spike, and suggests a process to prevent the stopper push-in from occurring. The
      study also shows that the human factor is another important element in the
      stopper push-in issue. It emphasizes the need for a joint effort for risk
      mitigation across the board among stopper manufacturers, spike manufacturers,
      pharmaceutical manufacturers, device manufacturers, and hospitals (pharmacies &
      healthcare workers). Device and drug developers need to properly select and test
      stoppers and containers with intended spikes. Healthcare workers need to use
      compatible stoppers and spikes, and need to use them correctly.

PMID- 30232138
TI  - The Histone Demethylase LSD1 Regulates B Cell Proliferation and Plasmablast
      Differentiation.
AB  - B cells undergo epigenetic remodeling as they differentiate into Ab-secreting
      cells (ASC). LSD1 is a histone demethylase known to decommission active enhancers
      and cooperate with the ASC master regulatory transcription factor Blimp-1. The
      contribution of LSD1 to ASC formation is poorly understood. In this study, we
      show that LSD1 is necessary for proliferation and differentiation of mouse naive
      B cells (nB) into plasmablasts (PB). Following LPS inoculation, LSD1-deficient
      hosts exhibited a 2-fold reduction of splenic PB and serum IgM. LSD1-deficient PB
      exhibited derepression and superinduction of genes involved in immune system
      processes; a subset of these being direct Blimp-1 target-repressed genes. Cell
      cycle genes were globally downregulated without LSD1, which corresponded to a
      decrease in the proliferative capacity of LSD1-deficient activated B cells. PB
      lacking LSD1 displayed increased histone H3 lysine 4 monomethylation and
      chromatin accessibility at nB active enhancers and the binding sites of
      transcription factors Blimp-1, PU.1, and IRF4 that mapped to LSD1-repressed
      genes. Together, these data show that LSD1 is required for normal in vivo PB
      formation, distinguish LSD1 as a transcriptional rheostat and epigenetic modifier
      of B cell differentiation, and identify LSD1 as a factor responsible for
      decommissioning nB active enhancers.

PMID- 30232141
TI  - Achieving "Zero" Defects for Visible Particles in Injectables.
AB  - The reduction of visible particles in injectable products is an important element
      in the consistent delivery of high-quality parenteral products. An important part
      of this effort is the control of particles that may emanate from the primary
      packaging materials. The Parenteral Drug Association (PDA), with the support of
      the Pharmaceutical Manufacturers Forum (PMF), has undertaken the task of
      developing test methods to assess the cleanliness of primary packaging components
      used in the manufacturing of sterile injectable products. Further work is focused
      on end-to-end analysis of the supply chain to identify additional points where
      particles may enter the finished product workflow. This includes shipment,
      receipt, transfer, and fill and finishing operations. This information and
      appropriate corrective actions and control methods, coupled with appropriate
      patient risk-based acceptance limits, are intended to provide better and more
      consistent supply of injectable products that meet current compendial and good
      manufacturing practice (GMP) expectations. Aligning control limits between
      supplier and pharmaceutical manufacturers will offer further improvement. This
      paper describes the formation of a task force to address these needs and current
      progress to date.LAY ABSTRACT: Visible particles must be controlled in parenteral
      products. Such particles come from many sources including the primary packaging
      materials. The Parenteral Drug Association (PDA), with the support of the
      Pharmaceutical Manufacturers Forum (PMF), has formed a task force to review and
      improve particle measurement methods and perform an end-to-end analysis of how
      particles may enter into parenteral products. These activities are intended to
      lead to more consistent control limits for visible particles and ultimately more
      consistent supply of high quality injectable products.

PMID- 30232142
TI  - Extraction/leaching of metal containing additives from polyvinyl chloride, ethyl
      vinyl acetate, and polypropylene bags and infusion sets into infusion solutions.
AB  - Flexible medical devices are primarily made of plasticized polyvinyl chloride
      (PVC). Lately, PVC is being replaced with ethyl vinyl acetate (EVA) and
      polypropylene (PP) to avoid undesired migration of the PVC plasticizers.
      Nevertheless, other additives are necessary to generate useful polymeric
      materials. Metallic species present in such additives can also leach out into the
      infusion solutions. The migration of Ba, Cd, Sn, Pb, and Zn from devices made
      from PVC, EVA, and PP was evaluated. Bags and infusion sets were decomposed, and
      their metallic contents were analyzed. Glucose, NaCl, and Tween 80 were
      investigated as extraction media. These solutions were stored in PVC, EVA, and PP
      bags, heat sterilized, and stored for eight months at room temperature. Aliquots
      were taken before and after sterilization and then once per month to determine
      the contents of the metals. Commercial glucose and NaCl infusions were analyzed
      by taking aliquots of the solutions from the bags and from the administration set
      after their administration to patients. The three polymers contained the five
      metals. Ba was found in the highest concentration in all samples, with a mean of
      8.0 mg/kg in PVC, 4.2 mg/kg in EVA, and 4.7 mg/kg in PP samples. Despite this,
      the only element that migrated into the glucose, NaCl, and Tween 80 solutions was
      Zn. The same result was found for the commercial glucose and NaCl infusions.
      Moreover, the Zn concentration in the administration sets was on average 52%
      higher than what was found in the bags.

PMID- 30232143
TI  - Androgen Receptor Inhibitor Enhances the Antitumor Effect of PARP Inhibitor in
      Breast Cancer Cells by Modulating DNA Damage Response.
AB  - The androgen receptor (AR) is expressed in 60%-70% of breast cancers regardless
      of estrogen receptor status, and has been proposed as a therapeutic target in
      breast cancers that retain AR. In this study, the authors aimed to investigate a
      new treatment strategy using a novel AR inhibitor AZD3514 in breast cancer.
      AZD3514 alone had a minimal antiproliferative effect on most breast cancer cell
      lines irrespective of AR expression level, but it downregulated the expressions
      of DNA damage response (DDR) molecules, including ATM and chk2, which resulted in
      the accumulation of damaged DNA in some breast cancer cells. Furthermore, AZD3514
      enhanced cellular sensitivity to a PARP inhibitor olaparib by blocking the DDR
      pathway in breast cancer cells. Furthermore, the downregulation of NKX3.1
      expression in MDA-MB-468 cells by AZD3514 occurred in parallel with the
      suppression of ATM-chk2 axis activation, and the suppression of NKX3.1 by AZD3514
      was found to result from AZD3514-induced TOPORS upregulation and a resultant
      increase in NKX3.1 degradation. The study shows posttranslational regulation of
      NKX3.1 via TOPORS upregulation by AZD3514-induced ATM inactivation-increased
      olaparib sensitivity in AR-positive and TOPORS-expressing breast cancer cells,
      and suggests the antitumor effect of AZD3514/olaparib cotreatment is caused by
      compromised DDR activity in breast cancer cell lines and in a xenograft model.
      These results provide a rationale for future clinical trials of olaparib/AR
      inhibitor combination treatment in breast cancer.

PMID- 30232144
TI  - Augmentation of the Enhanced Permeability and Retention Effect with Nitric Oxide
      Generating Agents Improves the Therapeutic Effects of Nanomedicines.
AB  - Enhanced permeability and retention (EPR) effect-based nanomedicine is a
      promising strategy for successful anticancer therapy. The EPR effect is based on
      tumor blood flow. Because advanced large tumors, as frequently seen in clinical
      settings, are heterogeneous, with regions of defective vasculature and blood
      flow, achieving the desired tumor drug delivery is difficult. Here, we utilized
      the EPR effect to increase drug delivery. To augment the EPR effect for improved
      therapeutic effects of nanomedicine, we exploited vascular mediators-the nitric
      oxide (NO) generators nitroglycerin (NG), hydroxyurea, and l-arginine. These
      compounds generate NO in tumors with relatively high selectivity. Using different
      nanosized drugs in our protocol significantly increased (1.5-2 times) delivery of
      nanomedicines to different solid tumor models, along with markedly improving (2-3
      fold) the antitumor effects of these drugs. Also, in 7,12
      dimethylbenz[a]anthracene-induced advanced end-stage breast cancer, often seen in
      clinical settings, 2 mg/kg polymer-conjugated pirarubicin (P-THP) with NG (0.2
      mg/mouse) showed better effects than did 5 mg/kg P-THP, and 5 mg/kg P-THP used
      with NG resulted in cures or stable tumors (no tumor growth) for up to 120 days.
      Moreover, in a murine autochthonous azoxymethane/dextran sulfate sodium-induced
      colon cancer model, NO donors markedly improved the therapeutic effects of P-THP
      even after just one injection, results that were comparable with those achieved
      with three weekly P-THP treatments. These findings strongly suggest the potential
      usefulness of NO donors as EPR effect enhancers to improve the therapeutic
      efficacy of nanomedicines.

PMID- 30232147
TI  - The Widespread Network Effects of Focal Epilepsy.

PMID- 30232145
TI  - Histone Deacetylase Inhibitors Synergize with Catalytic Inhibitors of EZH2 to
      Exhibit Antitumor Activity in Small Cell Carcinoma of the Ovary, Hypercalcemic
      Type.
AB  - Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but
      extremely lethal malignancy that mainly impacts young women. SCCOHT is
      characterized by a diploid genome with loss of SMARCA4 and lack of SMARCA2
      expression, two mutually exclusive ATPases of the SWI/SNF chromatin-remodeling
      complex. We and others have identified the histone methyltransferase EZH2 as a
      promising therapeutic target for SCCOHT, suggesting that SCCOHT cells depend on
      the alternation of epigenetic pathways for survival. In this study, we found that
      SCCOHT cells were more sensitive to pan-HDAC inhibitors compared with other
      ovarian cancer lines or immortalized cell lines tested. Pan-HDAC inhibitors, such
      as quisinostat, reversed the expression of a group of proteins that were
      deregulated in SCCOHT cells due to SMARCA4 loss, leading to growth arrest,
      apoptosis, and differentiation in vitro and suppressed tumor growth of
      xenografted tumors of SCCOHT cells. Moreover, combined treatment of HDAC
      inhibitors and EZH2 inhibitors at sublethal doses synergistically induced histone
      H3K27 acetylation and target gene expression, leading to rapid induction of
      apoptosis and growth suppression of SCCOHT cells and xenografted tumors.
      Therefore, our preclinical study highlighted the therapeutic potential of
      combined treatment of HDAC inhibitors with EZH2 catalytic inhibitors to treat
      SCCOHT.

PMID- 30232146
TI  - Characterization of the Selective Indoleamine 2,3-Dioxygenase-1 (IDO1) Catalytic
      Inhibitor EOS200271/PF-06840003 Supports IDO1 as a Critical Resistance Mechanism
      to PD-(L)1 Blockade Therapy.
AB  - Tumors use indoleamine 2,3-dioxygenase-1 (IDO1) as a major mechanism to induce an
      immunosuppressive microenvironment. IDO1 expression is upregulated in many
      cancers and considered to be a resistance mechanism to immune checkpoint
      therapies. IDO1 is induced in response to inflammatory stimuli such as IFNgamma
      and promotes immune tolerance by depleting tryptophan and producing tryptophan
      catabolites, including kynurenine, in the tumor microenvironment. This leads to
      effector T-cell anergy and enhanced Treg function through upregulation of FoxP3.
      As a nexus for the induction of key immunosuppressive mechanisms, IDO1 represents
      an important immunotherapeutic target in oncology. Here, we report the
      identification and characterization of the novel selective, orally bioavailable
      IDO1 inhibitor EOS200271/PF-06840003. It reversed IDO1-induced T-cell anergy in
      vitro In mice carrying syngeneic tumor grafts, PF-06840003 reduced intratumoral
      kynurenine levels by over 80% and inhibited tumor growth both in monotherapy and,
      with an increased efficacy, in combination with antibodies blocking the immune
      checkpoint ligand PD-L1. We demonstrate that anti-PD-L1 therapy results in
      increased IDO1 metabolic activity thereby providing additional mechanistic
      rationale for combining PD-(L)1 blockade with IDO1 inhibition in cancer
      immunotherapies. Supported by these preclinical data and favorable predicted
      human pharmacokinetic properties of PF-06840003, a phase I open-label,
      multicenter clinical study (NCT02764151) has been initiated.

PMID- 30232149
TI  - Towards evidence-based medicine for paediatricians.

PMID- 30232151
TI  - Impact of radiology reports on timely tuberculosis diagnosis.
AB  - PURPOSE: As tuberculosis becomes less common in higher income countries,
      clinician familiarity with the disease is declining. Little is known about how
      chest radiograph interpretations affect tuberculosis care. We sought to determine
      how tuberculosis-related terminology in an initial chest radiograph reading
      impacted patient care. STUDY DESIGN: We examined a retrospective cohort of
      patients with pulmonary tuberculosis in North Carolina from 1 January 2011 to 31
      December 2014. Tuberculosis-related terminology was categorised into four
      mutually exclusive categories. The primary outcomes of interest were the time
      from the chest radiograph to (1) obtaining the first sputum specimen for acid
      fast smear and mycobacterial culture, and (2) initiation of antituberculous
      treatment. RESULTS: Of 550 available chest radiograph reports, 175 (31.8%)
      contained the word 'tuberculosis', 30 (5.5%) contained the word 'mycobacteria' or
      'granulomatous', 43 (7.8%) contained the word 'cavity', and 301 (54.7%) had none
      of the above terms mentioned. Patients with the word 'tuberculosis' in the
      radiology report had a significantly shorter time to collection of the initial
      sputum specimen for acid-fast smear and mycobacterial culture (median 2 days) and
      to the start of antituberculous treatment (median 4 days) than patients with none
      of the keywords. Use of the term 'cavity' in the report was associated with a
      shorter time to initiation of antituberculous treatment (median 4 days) than if
      none of the keywords were used. CONCLUSION: Chest radiograph reports that
      contained keywords for pulmonary tuberculosis, such as 'tuberculosis' or
      'cavity', were associated with less time to collection of sputum and
      antituberculous treatment.

PMID- 30232152
TI  - Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly.
AB  - Mitochondrial reactive oxygen species (ROS) production is a tightly regulated
      redox signal that transmits information from the organelle to the cell. Other
      mitochondrial signals, such as ATP, are sensed by enzymes, including the key
      metabolic sensor and regulator, AMP-activated protein kinase (AMPK). AMPK
      responds to the cellular ATP/AMP and ATP/ADP ratios by matching mitochondrial ATP
      production to demand. Previous reports proposed that AMPK activity also responds
      to ROS, by ROS acting on redox-sensitive cysteine residues (Cys-299/Cys-304) on
      the AMPK alpha subunit. This suggests an appealing model in which mitochondria
      fine-tune AMPK activity by both adenine nucleotide-dependent mechanisms and by
      redox signals. Here we assessed whether physiological levels of ROS directly
      alter AMPK activity. To this end we added exogenous hydrogen peroxide (H2O2) to
      cells and utilized the mitochondria-targeted redox cycler MitoParaquat to
      generate ROS within mitochondria without disrupting oxidative phosphorylation.
      Mitochondrial and cytosolic thiol oxidation was assessed by measuring
      peroxiredoxin dimerization and by redox-sensitive fluorescent proteins. Replacing
      the putative redox-active cysteine residues on AMPK alpha1 with alanines did not
      alter the response of AMPK to H2O2 In parallel with measurements of AMPK
      activity, we measured the cell ATP/ADP ratio. This allowed us to separate the
      effects on AMPK activity due to ROS production from those caused by changes in
      this ratio. We conclude that AMPK activity in response to redox changes is not
      due to direct action on AMPK itself, but is a secondary consequence of redox
      effects on other processes, such as mitochondrial ATP production.

PMID- 30232154
TI  - Helicobacter pylori-binding nonacid glycosphingolipids in the human stomach.
AB  - Helicobacter pylori has a number of well-characterized carbohydrate-binding
      adhesins (BabA, SabA, and LabA) that promote adhesion to the gastric mucosa. In
      contrast, information on the glycoconjugates present in the human stomach remains
      unavailable. Here, we used MS and binding of carbohydrate-recognizing ligands to
      characterize the glycosphingolipids of three human stomachs from individuals with
      different blood group phenotypes (O(Rh-)P, A(Rh+)P, and A(Rh+)p), focusing on
      compounds recognized by H. pylori We observed a high degree of structural
      complexity, and the composition of glycosphingolipids differed among individuals
      with different blood groups. The type 2 chain was the dominating core chain of
      the complex glycosphingolipids in the human stomach, in contrast to the complex
      glycosphingolipids in the human small intestine, which have mainly a type 1 core.
      H. pylori did not bind to the O(Rh-)P stomach glycosphingolipids, whose major
      complex glycosphingolipids were neolactotetraosylceramide, the Lex, Lea, and H
      type 2 pentaosylceramides, and the Ley hexaosylceramide. Several H. pylori
      binding compounds were present among the A(Rh+)P and A(Rh+)p stomach
      glycosphingolipids. Ligands for BabA-mediated binding of H. pylori were the Leb
      hexaosylceramide, the H type 1 pentaosylceramide, and the A type 1/ALeb
      heptaosylceramide. Additional H. pylori-binding glycosphingolipids recognized by
      BabA-deficient strains were lactosylceramide, lactotetraosylceramide, the x2
      pentaosylceramide, and neolactohexaosylceramide. Our characterization of human
      gastric receptors required for H. pylori adhesion provides a basis for the
      development of specific compounds that inhibit the binding of this bacterium to
      the human gastric mucosa.

PMID- 30232155
TI  - Punctuated plastome reduction and host-parasite horizontal gene transfer in the
      holoparasitic plant genus Aphyllon.
AB  - Foundational studies of chloroplast genome (plastome) evolution in parasitic
      plants have focused on broad trends across large clades, particularly among the
      Orobanchaceae, a species-rich and ecologically diverse family of root parasites.
      However, the extent to which such patterns and processes of plastome evolution,
      such as stepwise gene loss following the complete loss of photosynthesis (shift
      to holoparasitism), are detectable at shallow evolutionary time scale is largely
      unknown. We used genome skimming to assemble eight chloroplast genomes
      representing complete taxonomic sampling of Aphyllon sect. Aphyllon, a small
      clade within the Orobanchaceae that evolved approximately 6 Ma, long after the
      origin of holoparasitism. We show substantial plastome reduction occurred in the
      stem lineage, but subsequent change in plastome size, gene content, and structure
      has been relatively minimal, albeit detectable. This lends additional fine
      grained support to existing models of stepwise plastome reduction in
      holoparasitic plants. Additionally, we report phylogenetic evidence based on an
      rbcL gene tree and assembled 60+ kb fragments of the Aphyllon epigalium
      mitochondrial genome indicating host-to-parasite horizontal gene transfers
      (hpHGT) of several genes originating from the plastome of an ancient Galium host
      into the mitochondrial genome of a recent common ancestor of A. epigalium
      Ecologically, this evidence of hpHGT suggests that the host-parasite associations
      between Galium and A. epigalium have been stable at least since its subspecies
      diverged hundreds of thousands of years ago.

PMID- 30232153
TI  - Calcium-sensitive pyruvate dehydrogenase phosphatase is required for energy
      metabolism, growth, differentiation, and infectivity of Trypanosoma cruzi.
AB  - In vertebrate cells, mitochondrial Ca2+ uptake by the mitochondrial calcium
      uniporter (MCU) leads to Ca2+-mediated stimulation of an intramitochondrial
      pyruvate dehydrogenase phosphatase (PDP). This enzyme dephosphorylates serine
      residues in the E1alpha subunit of pyruvate dehydrogenase (PDH), thereby
      activating PDH and resulting in increased ATP production. Although a
      phosphorylation/dephosphorylation cycle for the E1alpha subunit of PDH from
      nonvertebrate organisms has been described, the Ca2+-mediated PDP activation has
      not been studied. In this work, we investigated the Ca2+ sensitivity of two
      recombinant PDPs from the protozoan human parasites Trypanosoma cruzi (TcPDP) and
      T. brucei (TbPDP) and generated a TcPDP-KO cell line to establish TcPDP's role in
      cell bioenergetics and survival. Moreover, the mitochondrial localization of the
      TcPDP was studied by CRISPR/Cas9-mediated endogenous tagging. Our results
      indicate that TcPDP and TbPDP both are Ca2+-sensitive phosphatases. Of note,
      TcPDP-KO epimastigotes exhibited increased levels of phosphorylated TcPDH, slower
      growth and lower oxygen consumption rates than control cells, an increased
      AMP/ATP ratio and autophagy under starvation conditions, and reduced
      differentiation into infective metacyclic forms. Furthermore, TcPDP-KO
      trypomastigotes were impaired in infecting cultured host cells. We conclude that
      TcPDP is a Ca2+-stimulated mitochondrial phosphatase that dephosphorylates TcPDH
      and is required for normal growth, differentiation, infectivity, and energy
      metabolism in T. cruzi Our results support the view that one of the main roles of
      the MCU is linked to the regulation of intramitochondrial dehydrogenases.

PMID- 30232157
TI  - Testing hypotheses for the function of the carnivoran baculum using finite
      element analysis.
AB  - The baculum (os penis) is a mineralized bone within the glans of the mammalian
      penis and is one of the most morphologically diverse structures in the mammal
      skeleton. Recent experimental work provides compelling evidence for sexual
      selection shaping the baculum, yet the functional mechanism by which this occurs
      remains unknown. Previous studies have tested biomechanical hypotheses for the
      role of the baculum based on simple metrics such as length and diameter, ignoring
      the wealth of additional shape complexity present. For the first time, to our
      knowledge, we apply a computational simulation approach (finite-element analysis;
      FEA) to quantify the three-dimensional biomechanical performance of carnivoran
      bacula (n = 74) based upon high-resolution micro-computed tomography scans. We
      find a marginally significant positive correlation between sexual size dimorphism
      and baculum stress under compressive loading, counter to the 'vaginal friction'
      hypothesis of bacula becoming more robust to overcome resistance during initial
      intromission. However, a highly significant negative relationship exists between
      intromission duration and baculum stress under dorsoventral bending. Furthermore,
      additional FEA simulations confirm that the presence of a ventral groove would
      reduce deformation of the urethra. We take this as evidence in support of the
      'prolonged intromission' hypothesis, suggesting the carnivoran baculum has
      evolved in response to pressures on the duration of copulation and protection of
      the urethra.

PMID- 30232156
TI  - The ecology of movement and behaviour: a saturated tripartite network for
      describing animal contacts.
AB  - Ecologists regularly use animal contact networks to describe interactions
      underlying pathogen transmission, gene flow, and information transfer. However,
      empirical descriptions of contact often overlook some features of individual
      movement, and decisions about what kind of network to use in a particular setting
      are commonly ad hoc Here, we relate individual movement trajectories to contact
      networks through a tripartite network model of individual, space, and time nodes.
      Most networks used in animal contact studies (e.g. individual association
      networks, home range overlap networks, and spatial networks) are simplifications
      of this tripartite model. The tripartite structure can incorporate a broad suite
      of alternative ecological metrics like home range sizes and patch occupancy
      patterns into inferences about contact network metrics such as modularity and
      degree distribution. We demonstrate the model's utility with two simulation
      studies using alternative forms of ecological data to constrain the tripartite
      network's structure and inform expectations about the harder-to-measure metrics
      related to contact.

PMID- 30232158
TI  - Sexual selection on multiple female ornaments in dance flies.
AB  - Sex-specific ornaments typically occur in males, but they can also develop in
      females. While there are several models concerning the evolution of male-specific
      ornaments, it is not clear how, or under what circumstances, those models apply
      to female-specific ornament evolution. Here, we present a manipulative field
      experiment that explores the theoretical 'trait space' of multiple female
      specific ornaments to study how these unusual traits evolved. We measured the
      attractiveness of two female-specific ornaments (pinnate leg scales and
      inflatable abdominal sacs) in the dance fly Rhamphomyia longicauda in a wild
      mating swarm. We found significant directional preferences for larger ornaments
      of both types; however, variation in one of the ornaments (abdominal sacs) was
      almost three times more effective at improving attractiveness. The abdominal
      ornament was consistently effective in increasing attractiveness to males
      regardless of leg ornament expression, while leg ornament size was only effective
      if abdominal ornaments were very small. These results are consistent with
      predictions from a sexual conflict model of ornament expression in supporting the
      probable role of deception in the evolution of female-specific ornaments among
      dance flies. Sexual conflict can be an important force in generating elaborate
      sex-specific ornaments in females as well as males.

PMID- 30232159
TI  - Extinction risk in extant marine species integrating palaeontological and
      biodistributional data.
AB  - Extinction risk assessments of marine invertebrate species remain scarce, which
      hinders effective management of marine biodiversity in the face of anthropogenic
      impacts. To help close this information gap, in this paper we provide a metric of
      relative extinction risk that combines palaeontological data, in the form of
      extinction rates calculated from the fossil record, with two known correlates of
      risk in the modern day: geographical range size and realized thermal niche. We
      test the performance of this metric-Palaeontological Extinction Risk In Lineages
      (PERIL)-using survivorship analyses of Pliocene bivalve faunas from California
      and New Zealand, and then use it to identify present-day hotspots of extinction
      vulnerability for extant shallow-marine Bivalvia. Areas of the ocean where
      concentrations of bivalve species with higher PERIL scores overlap with high
      levels of climatic or anthropogenic stressors should be considered of most
      immediate concern for both conservation and management.

PMID- 30232160
TI  - Single mechanosensory neurons encode lateral displacements using precise spike
      timing and thresholds.
AB  - During locomotion, animals rely on multiple sensory modalities to maintain
      stability. External cues may guide behaviour, but they must be interpreted in the
      context of the animal's own body movements. Mechanosensory cues that can resolve
      dynamic internal and environmental conditions, like those from vertebrate
      vestibular systems or other proprioceptors, are essential for guided movement.
      How do afferent proprioceptor neurons transform movement into a neural code? In
      flies, modified hindwings known as halteres detect forces produced by body
      rotations and are essential for flight. However, the mechanisms by which haltere
      neurons transform forces resulting from three-dimensional body rotations into
      patterns of neural spikes are unknown. We use intracellular electrodes to record
      from haltere primary afferent neurons during a range of haltere motions. We find
      that spike timing activity of individual neurons changes with displacement and
      propose a mechanism by which single neurons can encode three-dimensional haltere
      movements during flight.

PMID- 30232161
TI  - Bottlenose dolphins can understand their partner's role in a cooperative task.
AB  - In recent decades, a number of studies have examined whether various non-human
      animals understand their partner's role in cooperative situations. Yet the
      relatively tolerant timing requirements of these tasks make it theoretically
      possible for animals to succeed by using simple behavioural strategies rather
      than by jointly intended coordination. Here we investigated whether bottlenose
      dolphins could understand a cooperative partner's role by testing whether they
      could learn a button-pressing task requiring precise behavioural synchronization.
      Specifically, members of cooperative dyads were required to swim across a lagoon
      and each press their own underwater button simultaneously (within a 1 s time
      window), whether sent together or with a delay between partners of 1-20 s. We
      found that dolphins were able to work together with extreme precision even when
      they had to wait for their partner, and that their coordination improved over the
      course of the study, with the time between button presses in the latter trials
      averaging 370 ms. These findings show that bottlenose dolphins can learn to
      understand their partner's role in a cooperative situation, and suggest that the
      behavioural synchronization evident in wild dolphins' synchronous movement and
      coordinated alliance displays may be a generalized cognitive ability that can
      also be used to solve novel cooperative tasks.

PMID- 30232162
TI  - Social tipping points in animal societies.
AB  - Animal social groups are complex systems that are likely to exhibit tipping
      points-which are defined as drastic shifts in the dynamics of systems that arise
      from small changes in environmental conditions-yet this concept has not been
      carefully applied to these systems. Here, we summarize the concepts behind
      tipping points and describe instances in which they are likely to occur in animal
      societies. We also offer ways in which the study of social tipping points can
      open up new lines of inquiry in behavioural ecology and generate novel questions,
      methods, and approaches in animal behaviour and other fields, including community
      and ecosystem ecology. While some behaviours of living systems are hard to
      predict, we argue that probing tipping points across animal societies and across
      tiers of biological organization-populations, communities, ecosystems-may help to
      reveal principles that transcend traditional disciplinary boundaries.

PMID- 30232163
TI  - Protein palmitoylation and cancer.
AB  - Protein S-palmitoylation is a reversible post-translational modification that
      alters the localization, stability, and function of hundreds of proteins in the
      cell. S-palmitoylation is essential for the function of both oncogenes (e.g.,
      NRAS and EGFR) and tumor suppressors (e.g., SCRIB, melanocortin 1 receptor). In
      mammalian cells, the thioesterification of palmitate to internal cysteine
      residues is catalyzed by 23 Asp-His-His-Cys (DHHC)-family palmitoyl S
      acyltransferases while the removal of palmitate is catalyzed by serine
      hydrolases, including acyl-protein thioesterases (APTs). These enzymes modulate
      the function of important oncogenes and tumor suppressors and often display
      altered expression patterns in cancer. Targeting S-palmitoylation or the enzymes
      responsible for palmitoylation dynamics may therefore represent a candidate
      therapeutic strategy for certain cancers.

PMID- 30232165
TI  - Complete Genome Sequence of a blaKPC-2-Positive Klebsiella pneumoniae Strain
      Isolated from the Effluent of an Urban Sewage Treatment Plant in Japan.
AB  - Antimicrobial resistance genes (ARGs) and the bacteria that harbor them are
      widely distributed in the environment, especially in surface water, sewage
      treatment plant effluent, soil, and animal waste. In this study, we isolated a
      KPC-2-producing Klebsiella pneumoniae strain (GSU10-3) from a sampling site in
      Tokyo Bay, Japan, near a wastewater treatment plant (WWTP) and determined its
      complete genome sequence. Strain GSU10-3 is resistant to most beta-lactam
      antibiotics and other antimicrobial agents (quinolones and aminoglycosides). This
      strain is classified as sequence type 11 (ST11), and a core genome phylogenetic
      analysis indicated that strain GSU10-3 is closely related to KPC-2-positive
      Chinese clinical isolates from 2011 to 2017 and is clearly distinct from strains
      isolated from the European Union (EU), United States, and other Asian countries.
      Strain GSU10-3 harbors four plasmids, including a blaKPC-2-positive plasmid,
      pGSU10-3-3 (66.2 kb), which is smaller than other blaKPC-2-positive plasmids and
      notably carries dual replicons (IncFII [pHN7A8] and IncN). Such downsizing and
      the presence of dual replicons may promote its maintenance and stable
      replication, contributing to its broad host range with low fitness costs. A
      second plasmid, pGSU10-3-1 (159.0 kb), an IncA/C2 replicon, carries a class 1
      integron (containing intI1, dfrA12, aadA2, qacEDelta1, and sul1) with a high
      degree of similarity to a broad-host-range plasmid present in the family
      Enterobacteriaceae The plasmid pGSU10-3-2 (134.8 kb), an IncFII(K) replicon,
      carries the IS26-mediated ARGs [aac(6')Ib-cr,blaOXA-1, catB4 (truncated), and
      aac(3)-IId], tet(A), and a copper/arsenate resistance locus. GSU10-3 is the first
      nonclinical KPC-2-producing environmental Enterobacteriaceae isolate from Japan
      for which the whole genome has been sequenced.IMPORTANCE We isolated and
      determined the complete genome sequence of a KPC-2-producing K. pneumoniae strain
      from a sampling site in Tokyo Bay, Japan, near a wastewater treatment plant
      (WWTP). In Japan, the KPC type has been very rarely detected, while IMP is the
      most predominant type of carbapenemase in clinical carbapenemase-producing
      Enterobacteriaceae (CPE) isolates. Although laboratory testing thus far suggested
      that Japan may be virtually free of KPC-producing Enterobacteriaceae, we have
      detected it from effluent from a WWTP. Antimicrobial resistance (AMR) monitoring
      of WWTP effluent may contribute to the early detection of future AMR bacterial
      dissemination in clinical settings and communities; indeed, it will help
      illuminate the whole picture in which environmental contamination through WWTP
      effluent plays a part.

PMID- 30232164
TI  - The Interferon-Induced Exonuclease ISG20 Exerts Antiviral Activity through
      Upregulation of Type I Interferon Response Proteins.
AB  - Type I interferon (IFN)-stimulated genes (ISGs) have critical roles in inhibiting
      virus replication and dissemination. Despite advances in understanding the
      molecular basis of ISG restriction, the antiviral mechanisms of many remain
      unclear. The 20-kDa ISG ISG20 is a nuclear 3'-5' exonuclease with preference for
      single-stranded RNA (ssRNA) and has been implicated in the IFN-mediated
      restriction of several RNA viruses. Although the exonuclease activity of ISG20
      has been shown to degrade viral RNA in vitro, evidence has yet to be presented
      that virus inhibition in cells requires this activity. Here, we utilized a
      combination of an inducible, ectopic expression system and newly generated Isg20
      /- mice to investigate mechanisms and consequences of ISG20-mediated restriction.
      Ectopically expressed ISG20 localized primarily to Cajal bodies in the nucleus
      and restricted replication of chikungunya and Venezuelan equine encephalitis
      viruses. Although restriction by ISG20 was associated with inhibition of
      translation of infecting genomic RNA, degradation of viral RNAs was not observed.
      Instead, translation inhibition of viral RNA was associated with ISG20-induced
      upregulation of over 100 other genes, many of which encode known antiviral
      effectors. ISG20 modulated the production of IFIT1, an ISG that suppresses
      translation of alphavirus RNAs. Consistent with this observation, the
      pathogenicity of IFIT1-sensitive alphaviruses was increased in Isg20-/- mice
      compared to that of wild-type viruses but not in cells ectopically expressing
      ISG20. Our findings establish an indirect role for ISG20 in the early restriction
      of RNA virus replication by regulating expression of other ISGs that inhibit
      translation and possibly other activities in the replication cycle.IMPORTANCE The
      host immune responses to infection lead to the production of type I interferon
      (IFN), and the upregulation of interferon-stimulated genes (ISGs) reduces virus
      replication and virus dissemination within a host. Ectopic expression of the
      interferon-induced 20-kDa exonuclease ISG20 suppressed replication of chikungunya
      virus and Venezuelan equine encephalitis virus, two mosquito-vectored RNA
      alphaviruses. Since the replication of alphavirus genomes occurs exclusively in
      the cytoplasm, the mechanism of nucleus-localized ISG20 inhibition of replication
      is unclear. In this study, we determined that ISG20 acts as a master regulator of
      over 100 genes, many of which are ISGs. Specifically, ISG20 upregulated IFIT1
      genes and inhibited translation of the alphavirus genome. Furthermore, IFIT1
      sensitive alphavirus replication was increased in Isg20-/- mice compared to the
      replication of wild-type viruses but not in cells ectopically expressing ISG20.
      We propose that ISG20 acts as an indirect regulator of RNA virus replication in
      the cytoplasm through the upregulation of many other ISGs.

PMID- 30232166
TI  - The Toxoplasma gondii Active Serine Hydrolase 4 Regulates Parasite Division and
      Intravacuolar Parasite Architecture.
AB  - Hydrolase are enzymes that regulate diverse biological processes, including
      posttranslational protein modifications. Recent work identified four active
      serine hydrolases (ASHs) in Toxoplasma gondii as candidate depalmitoylases.
      However, only TgPPT1 (ASH1) has been confirmed to remove palmitate from proteins.
      ASH4 (TgME49_264290) was reported to be refractory to genetic disruption. We
      demonstrate that recombinant ASH4 is an esterase that processes short acyl esters
      but not palmitoyl thioesters. Genetic disruption of ASH4 causes defects in cell
      division and premature scission of parasites from residual bodies. These defects
      lead to the presence of vacuoles with a disordered intravacuolar architecture,
      with parasites arranged in pairs around multiple residual bodies. Importantly, we
      found that the deletion of ASH4 correlates with a defect in radial dispersion
      from host cells after egress. This defect in dispersion of parasites is a general
      phenomenon that is observed for disordered vacuoles that occur at low frequency
      in wild-type parasites, suggesting a possible general link between intravacuolar
      organization and dispersion after egress.IMPORTANCE This work defines the
      function of an enzyme in the obligate intracellular parasite Toxoplasma gondii We
      show that this previously uncharacterized enzyme is critical for aspects of
      cellular division by the parasite and that loss of this enzyme leads to parasites
      with cell division defects and which also are disorganized inside their vacuoles.
      This leads to defects in the ability of the parasite to disseminate from the site
      of an infection and may have a significant impact on the parasite's overall
      infectivity of a host organism.

PMID- 30232167
TI  - Bats Are an Untapped System for Understanding Microbiome Evolution in Mammals.
AB  - Mammals evolved in a microbial world, and consequently, microbial symbionts have
      played a role in their evolution. An exciting new subdiscipline of metagenomics
      considers the ways in which microbes, particularly those found in the gut, have
      facilitated the ecological and phylogenetic radiation of mammals. However, the
      vast majority of such studies focus on domestic animals, laboratory models, or
      charismatic megafauna (e.g., pandas and chimpanzees). The result is a plethora of
      studies covering few taxa across the mammal tree of life, leaving broad patterns
      of microbiome function and evolution unclear. Wildlife microbiome research
      urgently needs a model system in which to test hypotheses about metagenomic
      involvement in host ecology and evolution. We propose that bats (Order:
      Chiroptera) represent a model system ideal for comparative microbiome research,
      affording opportunities to examine host phylogeny, diet, and other natural
      history characteristics in relation to the evolution of the gut microbiome.

PMID- 30232170
TI  - Erratum for Williams et al., "Investigation of the Plasma Virome from Cases of
      Unexplained Febrile Illness in Tanzania from 2013 to 2014: a Comparative Analysis
      between Unbiased and VirCapSeq-VERT High-Throughput Sequencing Approaches".

PMID- 30232168
TI  - Minicells as a Damage Disposal Mechanism in Escherichia coli.
AB  - Many bacteria produce small, spherical minicells that lack chromosomal DNA and
      therefore are unable to proliferate. Although minicells have been used
      extensively by researchers as a molecular tool, nothing is known about why
      bacteria produce them. Here, we show that minicells help Escherichia coli cells
      to rid themselves of damaged proteins induced by antibiotic stress. By comparing
      the survival and growth rates of wild-type strains with the E. coliDeltaminC
      mutant, which produces excess minicells, we found that the mutant was more
      resistant to streptomycin. To determine the effects of producing minicells at the
      single-cell level, we also tracked the growth of DeltaminC lineages by
      microscopy. We were able to show that the mutant increased the production of
      minicells in response to a higher level of the antibiotic. When we compared two
      sister cells, in which one produced minicells and the other did not, the
      daughters of the former had a shorter doubling time at this higher antibiotic
      level. Additionally, we found that minicells were more likely produced at the
      mother's old pole, which is known to accumulate more aggregates. More
      importantly, by using a fluorescent IbpA chaperone to tag damage aggregates, we
      found that polar aggregates were contained by and ejected with the minicells
      produced by the mother bacterium. These results demonstrate for the first time
      the benefit to bacteria for producing minicells.IMPORTANCE Bacteria have the
      ability to produce minicells, or small spherical versions of themselves that lack
      chromosomal DNA and are unable to replicate. A minicell can constitute as much as
      20% of the cell's volume. Although molecular biology and biotechnology have used
      minicells as laboratory tools for several decades, it is still puzzling that
      bacteria should produce such costly but potentially nonfunctional structures.
      Here, we show that bacteria gain a benefit by producing minicells and using them
      as a mechanism to eliminate damaged or oxidated proteins. The elimination allows
      the bacteria to tolerate higher levels of stress, such as increasing levels of
      streptomycin. If this mechanism extends from streptomycin to other antibiotics,
      minicell production could be an overlooked pathway that bacteria are using to
      resist antimicrobials.

PMID- 30232169
TI  - Deep Sequencing of H7N9 Influenza A Viruses from 16 Infected Patients from 2013
      to 2015 in Shanghai Reveals Genetic Diversity and Antigenic Drift.
AB  - Influenza A virus (IAV) infections are a major public health concern, including
      annual epidemics, epizootic outbreaks, and pandemics. A significant IAV epizootic
      outbreak was the H7N9 avian influenza A outbreak in China, which was first
      detected in 2013 and which has spread over 5 waves from 2013 to 2017, causing
      human infections in many different Chinese provinces. Here, RNA from primary
      clinical throat swab samples from 20 H7N9-infected local patients with different
      clinical outcomes, who were admitted and treated at one hospital in Shanghai,
      China, from April 2013 to April 2015, was analyzed. Whole-transcriptome
      amplification, with positive enrichment of IAV RNA, was performed, all 20 samples
      were subjected to deep sequencing, and data from 16 samples were analyzed in
      detail. Many single-nucleotide polymorphisms, including ones not previously
      reported, and many nonsynonymous changes that could affect hemagglutinin head and
      stalk antibody binding epitopes were observed. Minor populations representing
      viral quasispecies, including nonsynonymous hemagglutinin changes shared by
      antigenically variant H7N9 clades identified in the most recent wave of H7N9
      infections in 2016 to 2017, were also identified.IMPORTANCE H7N9 subtype avian
      influenza viruses caused infections in over 1,400 humans from 2013 to 2017 and
      resulted in almost 600 deaths. It is important to understand how avian influenza
      viruses infect and cause disease in humans and to assess their potential for
      efficient person-to-person transmission. In this study, we used deep sequencing
      of primary clinical material to assess the evolution and potential for human
      adaptation of H7N9 influenza viruses.

PMID- 30232172
TI  - Acanthamoeba keratitis: confirmation of the UK outbreak and a prospective case
      control study identifying contributing risk factors.
AB  - BACKGROUND/AIMS: Acanthamoeba keratitis (AK) is a chronic debilitating corneal
      infection principally affecting contact lens (CL) users. Studies were designed to
      test claims that the UK incidence may have increased in 2012-2014 and to evaluate
      potential causes. METHODS: Annualised incidence data were collected from January
      1984 to December 2016. Case-control study subjects were recruited between 14
      April 2011 and 05 June 2017. Reusable CL users with AK were recruited
      retrospectively and prospectively. Controls were reusable CL users, recruited
      prospectively, with any disorder other than AK. Multivariable analysis of
      questionnaire data measured independent risk factors for AK. RESULTS: The current
      outbreak of AK started in 2010-2011 with an incidence threefold higher than in
      2004-2009. Risk factors for AK were: Oxipol disinfection, CLs made of group IV CL
      materials, poor CL hygiene, deficient hand hygiene, use of CLs while swimming or
      bathing, being white British, and for those in social classes 4-9. CONCLUSION: AK
      is a largely preventable disease. The current outbreak is unlikely to be due to
      any one of the identified risk factors in isolation. Improving CL and hand
      hygiene, avoiding CLs contamination with water and use of effective CL
      disinfection solutions, or daily disposable CLs, will reduce the incidence of AK.
      In the longer-term, water avoidance publicity for CL users can be expected to
      reduce the incidence further. Ongoing surveillance of AK numbers will identify
      changes in incidence earlier. Evaluation of Acanthamoeba contamination in end
      user drinking water would contribute to our understanding of regional variations
      in the risk of exposure.

PMID- 30232171
TI  - Study of Optimal Perimetric Testing in Children (OPTIC): evaluation of kinetic
      approaches in childhood neuro-ophthalmic disease.
AB  - AIMS: We compared feasibility, quality and outcomes of visual field (VF) testing
      in children with neuro-ophthalmic disease between the discontinued 'gold
      standard' Goldmann and Octopus perimeters. METHODS: Children with neuro
      ophthalmic disease, attending Great Ormond Street Hospital, London, were assessed
      using standardised protocols by one examiner in a single sitting, using Goldmann
      and Octopus kinetic perimetry. Outputs were classified to compare severity of
      loss and defect type. Test quality was assessed using both qualitative and
      quantitative methods. RESULTS: Thirty children (40% female) aged 5-15 years
      participated. Goldmann perimetry was completed in full by 90.0% vs 72.4% for
      Octopus. Inability to plot the blind spot was the most common reason for not
      completing testing. Over 75% completed a test in <=20 min. Duration was similar
      between perimeters (paired t-test, mean difference: 0.48min (-1.2, 2.2),
      p=0.559). The lowest quality tests were for Octopus perimetry in children <8
      years, without significant differences between perimeters in older children
      (McNemar's test, chi2=1.0, p=0.317). There was broad agreement between Goldmann
      and Octopus outputs (good quality, n=21, Bland-Altman, mean difference for
      isopters I4e (-514.3  deg2 (-817.4, -211.2), p=0.814), I2e (-575.5 deg2 (-900.1, 
      250.9), p=0.450) and blind spot (20.8 deg2 (5.7, 35.8), p=0.451)). However, VF
      severity grades and defect type matched in only 57% and 69% of tests,
      respectively. Octopus perimetry underestimated severe VF defects. CONCLUSIONS:
      Informative perimetry is feasible in children >=8 years with neuro-ophthalmic
      conditions, with either Goldmann or Octopus perimeters. However, meaningful
      differences exist between the two approaches with implications for consistency in
      longitudinal assessments.

PMID- 30232175
TI  - Researcher cautions against initiatives to reduce student suicide that lack
      evidence.

PMID- 30232173
TI  - Single-cell murine genetic fate mapping reveals bipotential hepatoblasts and
      novel multi-organ endoderm progenitors.
AB  - The definitive endoderm (DE) is the embryonic germ layer that forms the gut tube
      and associated organs, including thymus, lungs, liver and pancreas. To understand
      how individual DE cells furnish gut organs, genetic fate mapping was performed
      using the Rosa26lacZ Cre-reporter paired with a tamoxifen-inducible DE-specific
      Cre-expressing transgene. We established a low tamoxifen dose that infrequently
      induced heritable lacZ expression in a single cell of individual E8.5 mouse
      embryos and identified clonal cell descendants at E16.5. As expected, only a
      fraction of the E16.5 embryos contained lacZ-positive clonal descendants and a
      subset of these contained descendants in multiple organs, revealing novel
      ontogeny. Furthermore, immunohistochemical analysis was used to identify lacZ
      positive hepatocytes and biliary epithelial cells, which are the cholangiocyte
      precursors, in each clonally populated liver. Together, these data not only
      uncover novel and suspected lineage relationships between DE-derived organs, but
      also illustrate the bipotential nature of individual hepatoblasts by
      demonstrating that single hepatoblasts contribute to both the hepatocyte and the
      cholangiocyte lineage in vivo.

PMID- 30232174
TI  - Decreased expression of pigment epithelium-derived factor within the penile
      tissues contributes to erectile dysfunction in diabetic rats.
AB  - Increased production of reactive oxygen species (ROS) and inflammation are major
      contributors to the development and progression of diabetes-associated erectile
      dysfunction (DMED). As an endogenous antioxidant and anti-inflammatory factor,
      the potential implication of pigment epithelium-derived factor (PEDF) in DMED has
      not been revealed. To assess the potential antioxidant and anti-inflammatory
      functions of PEDF in DMED, we first demonstrated that PEDF was significantly
      decreased at the levels of the mRNA and protein in the penis of diabetic rats
      compared with normal controls. To test the hypothesis that decreased the penile
      levels of PEDF are associated with oxidative stress and inflammation in DMED, an
      adenovirus expressing PEDF (Ad-PEDF) or the same titer of control virus (Ad-GFP)
      was intracavernously administered at 2 weeks after diabetic onset. After 6 weeks
      of treatment, we found that administration of Ad-PEDF could significantly
      increase erectile response to cavernosal nerve stimulation in the diabetic rats
      by restoring the endothelial NO synthase (eNOS), P-eNOS, and neuronal NO synthase
      (nNOS) protein levels to the standard levels represented in normal rats and by
      suppressing the levels of tumor necrosis factor-alpha (TNF-alpha) and oxidative
      stress. In conclusion, the present data indicated that the antioxidant and anti
      inflammatory potential of PEDF plays important role in restoring erectile
      function by the inhibition of oxidative stress and TNF-alpha production.

PMID- 30232176
TI  - Calcitriol and Calcipotriol Modulate Transport Activity of ABC Transporters and
      Exhibit Selective Cytotoxicity in MRP1-overexpressing Cells.
AB  - Efflux transporters P-glycoprotein (P-gp/ABCB1), multidrug resistance protein 1
      (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) can affect the
      efficacy and toxicity of a wide variety of drugs and are implicated in multidrug
      resistance (MDR). Eight test compounds, recently identified from an
      intramolecular FRET-based high throughput screening, were characterized for their
      interaction with MRP1. We report that the active metabolite of vitamin D3,
      calcitriol, and its analog calcipotriol are selectively cytotoxic to MRP1
      overexpressing cells, besides inhibiting transport function of P-gp, MRP1, and
      BCRP. Calcitriol and calcipotriol consistently displayed a potent inhibitory
      activity on MRP1-mediated doxorubicin and calcein efflux in MRP1-overexpressing
      H69AR and HEK293/MRP1 cells. Vesicular transport studies confirmed a strong
      inhibitory effect of calcitriol and calcipotriol on MRP1-mediated uptake of
      tritium-labeled estradiol glucuronide and leukotriene C4 In cytotoxicity assays,
      MRP1-overexpressing cells exhibited hypersensitivity toward calcitriol and
      calcipotriol. Such collateral sensitivity, however, was not observed in HEK293/P
      gp and HEK293/BCRP cells, although the vitamin D3 analogs inhibited calcein
      efflux in P-gp-overexpressing cells, and mitoxantrone efflux in BCRP
      overexpressing cells. The selective cytotoxicity of calcitriol and calpotriol
      toward MRP1 over-expressing cells can be eliminated with MRP1 inhibitor MK571.
      Our data indicate a potential role of calcitriol and its analogs in targeting
      malignancies in which MRP1 expression is prominent and contributes to MDR.

PMID- 30232177
TI  - Toward a Combinatorial Approach for the Prediction of IgG Half-Life and
      Clearance.
AB  - The serum half-life and clearance of therapeutic monoclonal antibodies (mAbs) are
      critical factors that impact their efficacy and optimal dosing regimen. The pH
      dependent binding of an mAb to the neonatal Fc receptor (FcRn) has long been
      recognized as an important determinant of its pharmacokinetics. However, FcRn
      affinity alone is not a reliable predictor of mAb half-life, suggesting that
      other biologic or biophysical mechanisms must be accounted for. mAb thermal
      stability, which reflects its unfolding and aggregation propensities, may also
      relate to its pharmacokinetic properties. However, no rigorous statistical
      regression methods have been used to identify combinations of physical parameters
      that best predict biologic properties. In this work, a panel of eight mAbs with
      published human pharmacokinetic data were selected for biophysical analyses of
      FcRn binding and thermal stability. Biolayer interferometry was used to
      characterize FcRn/mAb binding at acidic and neutral pH, while differential
      scanning calorimetry was used to determine thermodynamic unfolding parameters.
      Individual binding or stability parameters were generally weakly correlated with
      half-life and clearance values. Least absolute shrinkage and selection operator
      regression was used to identify the combination of two parameters with the best
      correlation to half-life and clearance as being the FcRn binding response at pH
      7.0 and the change in heat capacity. Leave-one-out subsampling yielded a root
      mean square difference between observed and predicted half-life of just 2.7 days
      (16%). Thus, the incorporation of multiple biophysical parameters into a cohesive
      model may facilitate early-stage prediction of in vivo half-life and clearance
      based on simple in vitro experiments.

PMID- 30232178
TI  - Molecular Characterization of the Viroporin Function of Foot-and-Mouth Disease
      Virus Nonstructural Protein 2B.
AB  - Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is
      comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function
      analyses demonstrated that FMDV 2B is an ion channel-forming protein. Infrared
      spectroscopy measurements using partially overlapping peptides that spanned
      regions between amino acids 28 and 147 demonstrated the adoption of helical
      conformations in two putative transmembrane regions between residues 60 and 78
      and between residues 119 and 147 and a third transmembrane region between
      residues 79 and 106, adopting a mainly extended structure. Using synthetic
      peptides, ion channel activity measurements in planar lipid bilayers and imaging
      of single giant unilamellar vesicles (GUVs) revealed the existence of two
      sequences endowed with membrane-porating activity: one spanning FMDV 2B residues
      55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to
      147. Mapping the latter sequence identified residues 119 to 147 as being
      responsible for the activity. Experiments to assess the degree of insertion of
      the synthetic peptides in bilayers and the inclination angle adopted by each
      peptide regarding the membrane plane normal confirm that residues 55 to 82 and
      119 to 147 of 2B actively insert as transmembrane helices. Using reverse
      genetics, a panel of 13 FMD recombinant mutant viruses was designed, which
      harbored nonconservative as well as alanine substitutions in critical amino acid
      residues in the area between amino acid residues 28 and 147. Alterations to any
      of these structures interfered with pore channel activity and the capacity of the
      protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal
      for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin
      family containing two distinct pore domains.IMPORTANCE FMDV nonstructural protein
      2B is able to insert itself into cellular membranes to form a pore. This pore
      allows the passage of ions and small molecules through the membrane. In this
      study, we were able to show that both current and small molecules are able to
      pass though the pore made by 2B. We also discovered for the first time a virus
      with a pore-forming protein that contains two independent functional pores. By
      making mutations in our infectious clone of FMDV, we determined that mutations in
      either pore resulted in nonviable virus. This suggests that both pore-forming
      functions are independently required during FMDV infection.

PMID- 30232179
TI  - A Novel Chimeric Oncolytic Virus Vector for Improved Safety and Efficacy as a
      Platform for the Treatment of Hepatocellular Carcinoma.
AB  - Oncolytic viruses represent an exciting new aspect of the evolving field of
      cancer immunotherapy. We have engineered a novel hybrid vector comprising
      vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV), named
      recombinant VSV-NDV (rVSV-NDV), wherein the VSV backbone is conserved but its
      glycoprotein has been replaced by the hemagglutinin-neuraminidase (HN) and the
      modified, hyperfusogenic fusion (F) envelope proteins of recombinant NDV. In
      comparison to wild-type VSV, which kills cells through a classical cytopathic
      effect, the recombinant virus is able to induce tumor-specific syncytium
      formation, allowing efficient cell-to-cell spread of the virus and a rapid onset
      of immunogenic cell death. Furthermore, the glycoprotein exchange substantially
      abrogates the off-target effects in brain and liver tissue associated with wild
      type VSV, resulting in a markedly enhanced safety profile, even in immune
      deficient NOD.CB17-prkdcscid/NCrCrl (NOD-SCID) mice, which are highly susceptible
      to wild-type VSV. Although NDV causes severe pathogenicity in its natural avian
      hosts, the incorporation of the envelope proteins in the chimeric rVSV-NDV vector
      is avirulent in embryonated chicken eggs. Finally, systemic administration of
      rVSV-NDV in orthotopic hepatocellular carcinoma (HCC)-bearing immune-competent
      mice resulted in significant survival prolongation. This strategy, therefore,
      combines the beneficial properties of the rapidly replicating VSV platform with
      the highly efficient spread and immunogenic cell death of a fusogenic virus
      without risking the safety and environmental threats associated with either
      parental vector. Taking the data together, rVSV-NDV represents an attractive
      vector platform for clinical translation as a safe and effective oncolytic
      virus.IMPORTANCE The therapeutic efficacy of oncolytic viral therapy often comes
      as a tradeoff with safety, such that potent vectors are often associated with
      toxicity, while safer viruses tend to have attenuated therapeutic effects.
      Despite promising preclinical data, the development of VSV as a clinical agent
      has been substantially hampered by the fact that severe neurotoxicity and
      hepatotoxicity have been observed in rodents and nonhuman primates in response to
      treatment with wild-type VSV. Although NDV has been shown to have an attractive
      safety profile in humans and to have promising oncolytic effects, its further
      development has been severely restricted due to the environmental risks that it
      poses. The hybrid rVSV-NDV vector, therefore, represents an extremely promising
      vector platform in that it has been rationally designed to be safe, with respect
      to both the recipient and the environment, while being simultaneously effective,
      both through its direct oncolytic actions and through induction of immunogenic
      cell death.

PMID- 30232180
TI  - Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse
      Model.
AB  - Influenza viruses and rhinoviruses are responsible for a large number of acute
      respiratory viral infections in human populations and are detected as copathogens
      within hosts. Clinical and epidemiological studies suggest that coinfection by
      rhinovirus and influenza virus may reduce disease severity and that they may also
      interfere with each other's spread within a host population. To determine how
      coinfection by these two unrelated respiratory viruses affects pathogenesis, we
      established a mouse model using a minor serogroup rhinovirus (rhinovirus strain
      1B [RV1B]) and mouse-adapted influenza A virus (A/Puerto Rico/8/1934 [PR8]).
      Infection of mice with RV1B 2 days before PR8 reduced the severity of infection
      by a low or medium, but not high, dose of PR8. Disease attenuation was associated
      with an early inflammatory response in the lungs and enhanced clearance of PR8.
      However, coinfection by RV1B did not reduce PR8 viral loads early in infection or
      inhibit replication of PR8 within respiratory epithelia or in vitro Inflammation
      in coinfected mice remained focal compared to diffuse inflammation and damage in
      the lungs of mice infected by PR8. The timing of RV1B coinfection was a critical
      determinant of protection, suggesting that sufficient time is needed to induce
      this response. Finally, disease attenuation was not unique to RV1B: dose
      dependent coinfection by a murine coronavirus (mouse hepatitis virus strain 1
      [MHV-1]) also reduced the severity of PR8 infection. Unlike RV1B, coinfection
      with MHV-1 reduced early PR8 replication, which was associated with upregulation
      of beta interferon (IFN-beta) expression. This model is critical for
      understanding the mechanisms responsible for influenza disease attenuation during
      coinfection by unrelated respiratory viruses.IMPORTANCE Viral infections in the
      respiratory tract can cause severe disease and are responsible for a majority of
      pediatric hospitalizations. Molecular diagnostics have revealed that
      approximately 20% of these patients are infected by more than one unrelated viral
      pathogen. To understand how viral coinfection affects disease severity, we
      inoculated mice with a mild viral pathogen (rhinovirus or murine coronavirus),
      followed 2 days later by a virulent viral pathogen (influenza A virus). This
      model demonstrated that rhinovirus can reduce the severity of influenza A virus,
      which corresponded with an early but controlled inflammatory response in the
      lungs and early clearance of influenza A virus. We further determined the dose
      and timing parameters that were important for effective disease attenuation and
      showed that influenza disease is also reduced by coinfection with a murine
      coronavirus. These findings demonstrate that coinfecting viruses can alter immune
      responses and pathogenesis in the respiratory tract.

PMID- 30232181
TI  - Redundant Late Domain Functions of Tandem VP2 YPX3L Motifs in Nonlytic Cellular
      Egress of Quasi-enveloped Hepatitis A Virus.
AB  - The quasi-envelopment of hepatitis A virus (HAV) capsids in exosome-like virions
      (eHAV) is an important but incompletely understood aspect of the hepatovirus life
      cycle. This process is driven by recruitment of newly assembled capsids to
      endosomal vesicles into which they bud to form multivesicular bodies with
      intraluminal vesicles that are later released at the plasma membrane as eHAV. The
      endosomal sorting complexes required for transport (ESCRT) are key to this
      process, as is the ESCRT-III-associated protein, ALIX, which also contributes to
      membrane budding of conventional enveloped viruses. YPX1or3L late domains in the
      structural proteins of these viruses mediate interactions with ALIX, and two such
      domains exist in the HAV VP2 capsid protein. Mutational studies of these domains
      are confounded by the fact that the Tyr residues (important for interactions of
      YPX1or3L peptides with ALIX) are required for efficient capsid assembly. However,
      single Leu-to-Ala substitutions within either VP2 YPX3L motif (L1-A and L2-A
      mutants) were well tolerated, albeit associated with significantly reduced eHAV
      release. In contrast, simultaneous substitutions in both motifs (L1,2-A)
      eliminated virus release but did not inhibit assembly of infectious intracellular
      particles. Immunoprecipitation experiments suggested that the loss of eHAV
      release was associated with a loss of ALIX recruitment. Collectively, these data
      indicate that HAV YPX3L motifs function as redundant late domains during quasi
      envelopment and viral release. Since these motifs present little solvent
      accessible area in the crystal structure of the naked extracellular capsid, the
      capsid structure may be substantially different during quasi
      envelopment.IMPORTANCE Nonlytic release of hepatitis A virus (HAV) as exosome
      like quasi-enveloped virions is a unique but incompletely understood aspect of
      the hepatovirus life cycle. Several lines of evidence indicate that the host
      protein ALIX is essential for this process. Tandem YPX3L "late domains" in the
      VP2 capsid protein could be sites of interaction with ALIX, but they are not
      accessible on the surface of an X-ray model of the extracellular capsid, raising
      doubts about this putative late domain function. Here, we describe YPX3L domain
      mutants that assemble capsids normally but fail to bind ALIX and be secreted as
      quasi-enveloped eHAV. Our data support late domain function for the VP2 YPX3L
      motifs and raise questions about the structure of the HAV capsid prior to and
      following quasi-envelopment.

PMID- 30232182
TI  - Cellular Protein Kinase D Modulators Play a Role during Multiple Steps of Herpes
      Simplex Virus 1 Egress.
AB  - The assembly of new herpes simplex virus 1 (HSV-1) particles takes place in the
      nucleus. These particles then travel across the two nuclear membranes and acquire
      a final envelope from a cellular compartment. The contribution of the cell to the
      release of the virus is, however, little known. We previously demonstrated, using
      a synchronized infection, that the host protein kinase D and diacylglycerol, a
      lipid that recruits the kinase to the trans-Golgi network (TGN), promote the
      release of the virus from that compartment. Given the role this cellular protein
      plays in the herpes simplex virus 1 life cycle and the many molecules that
      modulate its activity, we aimed to determine to what extent this virus utilizes
      the protein kinase D pathway during a nonsynchronized infection. Several
      molecular protein kinase D (PKD) regulators were targeted by RNA interference and
      viral production monitored. Surprisingly, many of these modulators negatively
      impacted the extracellular release of the virus. Overexpression studies, the use
      of pharmacological reagents, and assays to monitor intracellular lipids
      implicated in the biology of PKD suggested that these effects were oddly
      independent of total intracellular diacylglycerol levels. Instead, mapping of the
      viral intermediates by electron microscopy suggested that some of these
      modulators could regulate distinct steps along the viral egress pathway, notably
      nuclear egress. Altogether, this suggests a more complex contribution of PKD to
      HSV-1 egress than originally anticipated and new research avenues to
      explore.IMPORTANCE Viruses are obligatory parasites that highjack numerous
      cellular functions. This is certainly true when it comes to transporting viral
      particles within the cell. Herpesviruses share the unique property of traveling
      through the two nuclear membranes by subsequent budding and fusion and acquiring
      their final envelope from a cellular organelle. Albeit disputed, the overall
      evidence from many laboratories points to the trans-Golgi network (TGN) as the
      source of that membrane. Moreover, past findings revealed that the host protein
      kinase D (PKD) plays an important role at that stage, which is significant given
      the known implication of that protein in vesicular transport. The present
      findings suggest that the PKD machinery not only affects the late stages of
      herpes simplex virus I egress but also modulates earlier steps, such as nuclear
      egress. This opens up new means to control these viruses.

PMID- 30232183
TI  - T5 Exonuclease Hydrolysis of Hepatitis B Virus Replicative Intermediates Allows
      Reliable Quantification and Fast Drug Efficacy Testing of Covalently Closed
      Circular DNA by PCR.
AB  - Chronic infection with the human hepatitis B virus (HBV) is a major health
      problem. Virus persistence requires the establishment and maintenance of
      covalently closed circular DNA (cccDNA), the episomal virus template in the
      nucleus of infected hepatocytes. Compared to replicative DNA intermediates
      (relaxed circular DNA [rcDNA]), copy numbers of cccDNA in infected hepatocytes
      are low. Accordingly, accurate analyses of cccDNA require enrichment of nuclear
      fractions and Southern blotting or selective quantitative PCR (qPCR) methods
      allowing discrimination of cccDNA and rcDNA. In this report, we analyzed cccDNA
      specific primer pairs for their ability to amplify cccDNA selectively. Using
      mixtures of defined forms of HBV and genomic DNA, we determined the potential of
      different nucleases for targeted digestion of the open/relaxed circular DNA forms
      in the absence and presence of genomic DNA without affecting cccDNA. We found
      that the combination of T5 exonuclease with a primer set amplifying an
      approximately 1-kb fragment permits reliable quantification of cccDNA without the
      requirement of prior nucleus enrichment or Hirt extraction. We tested this method
      in four different in vitro infection systems and quantified cccDNA copy numbers
      at increasing multiplicities of inoculated genome equivalents. We further
      analyzed the kinetics of cccDNA formation and the effect of drugs (interferon,
      entry inhibitors, and capsid inhibitors) on cccDNA. Our method allows reliable
      cccDNA quantification at early stages of infection in the presence of a high
      excess of input virus and replicative intermediates and is thereby suitable for
      drug screening and investigation of cccDNA formation and maintenance.IMPORTANCE
      cccDNA elimination is a major goal in future curative regimens for chronic HBV
      patients. However, PCR-based assays for cccDNA quantification show a principally
      constrained specificity when high levels of input virus or replicative
      intermediates are present. Here, we characterized T5 exonuclease as a suitable
      enzyme for medium-throughput in vitro assays that preserves cccDNA but
      efficiently removes rcDNA prior to PCR-based quantification. We compared T5
      exonuclease with the previously described exonuclease III and showed that both
      nucleases are suitable for reliable quantification of cccDNA by PCR. We
      substantiated the applicability of our method through examination of early cccDNA
      formation and stable accumulation in several in vitro infection models and
      analyzed cccDNA stability after administration of anti-HBV drugs. Our results
      support the use of T5 exonuclease for fast and convenient rcDNA removal,
      especially for early cccDNA quantification and rapid drug testing in in vitro
      studies.

PMID- 30232184
TI  - Robust Human and Murine Hepatocyte Culture Models of Hepatitis B Virus Infection
      and Replication.
AB  - Hepatitis B virus (HBV) is a major cause of chronic liver diseases, including
      hepatitis, cirrhosis, and hepatocellular carcinoma. HBV research has been
      hampered by the lack of robust cell culture and small animal models of HBV
      infection. The discovery of sodium taurocholate cotransporting polypeptide (NTCP)
      as an HBV receptor has been a landmark advance in HBV research in recent years.
      Ectopic expression of NTCP in nonpermissive HepG2, Huh7, and AML12 cell lines
      confers HBV susceptibility. However, HBV replication in these human and murine
      hepatocyte cell lines appeared suboptimal. In the present study, we constructed
      stable NTCP-expressing HepG2 and AML12 cell lines and found that HBV
      permissiveness is correlated with NTCP expression. More significantly, we
      developed robust HBV cell culture models by treating the HBV-infected cells with
      dimethyl sulfoxide (DMSO) and hydrocortisone, which significantly promoted HBV
      replication and production. Mechanistic studies suggested that hydrocortisone
      significantly enhanced the transcription and expression of PGC1alpha and
      HNF4alpha, which are known to promote HBV transcription and replication. These
      new human and murine hepatocyte culture systems of HBV infection and replication
      will accelerate the determination of molecular aspects underlying HBV infection,
      replication, and morphogenesis in human and murine hepatocytes. We anticipate
      that our HBV cell culture models will also facilitate the discovery and
      development of antiviral drugs towards the ultimate eradication of chronic
      hepatitis B virus infection.IMPORTANCE HBV research has been greatly hampered by
      the lack of robust cell culture and small animal models of HBV infection and
      propagation. The discovery of NTCP as an HBV receptor has greatly impacted the
      field of HBV research. Although HBV infection of NTCP-expressing human and murine
      hepatocyte cell lines has been demonstrated, its replication in cell culture
      appeared inefficient. To further improve cell culture systems of HBV infection
      and replication, we constructed NTCP-expressing HepG2 and AML12 cell lines that
      are highly permissive to HBV infection. More significantly, we found that DMSO
      and hydrocortisone markedly enhanced HBV transcription and replication in human
      and murine hepatocytes when added to the cell culture medium. These new cell
      culture models of HBV infection and replication will facilitate HBV research and
      antiviral drug discovery towards the ultimate elimination of chronic hepatitis B
      virus infection.

PMID- 30232185
TI  - Structure-Guided Identification of a Nonhuman Morbillivirus with Zoonotic
      Potential.
AB  - Morbilliviruses infect a broad range of mammalian hosts, including ruminants,
      carnivores, and humans. The recent eradication of rinderpest virus (RPV) and the
      active campaigns for eradication of the human-specific measles virus (MeV) have
      raised significant concerns that the remaining morbilliviruses may emerge in so
      called vacated ecological niches. Seeking to assess the zoonotic potential of
      nonhuman morbilliviruses within human populations, we found that peste des petits
      ruminants virus (PPRV)-the small-ruminant morbillivirus-is restricted at the
      point of entry into human cells due to deficient interactions with human SLAMF1
      the immune cell receptor for morbilliviruses. Using a structure-guided approach,
      we characterized a single amino acid change, mapping to the receptor-binding
      domain in the PPRV hemagglutinin (H) protein, which overcomes this restriction.
      The same mutation allowed escape from some cross-protective, human patient, anti
      MeV antibodies, raising concerns that PPRV is a pathogen with zoonotic potential.
      Analysis of natural variation within human and ovine SLAMF1 also identified
      polymorphisms that could correlate with disease resistance. Finally, the
      mechanistic nature of the PPRV restriction was also investigated, identifying
      charge incompatibility and steric hindrance between PPRV H and human SLAMF1
      proteins. Importantly, this research was performed entirely using surrogate virus
      entry assays, negating the requirement for in situ derivation of a human-tropic
      PPRV and illustrating alternative strategies for identifying gain-of-function
      mutations in viral pathogens.IMPORTANCE A significant proportion of viral
      pandemics occur following zoonotic transmission events, where animal-associated
      viruses jump species into human populations. In order to provide forewarnings of
      the emergence of these viruses, it is necessary to develop a better understanding
      of what determines virus host range, often at the genetic and structural levels.
      In this study, we demonstrated that the small-ruminant morbillivirus, a close
      relative of measles, is unable to use human receptors to enter cells; however, a
      change of a single amino acid in the virus is sufficient to overcome this
      restriction. This information will be important for monitoring this virus's
      evolution in the field. Of note, this study was undertaken in vitro, without
      generation of a fully infectious virus with this phenotype.

PMID- 30232187
TI  - Toll Like Receptor-7 and -9 agonists improve Hepatitis C Virus replication and
      infectivity inhibition by plasmacytoid dendritic cells.
AB  - Plasmacytoid dendritic cells (pDCs) are innate immune cells with high antiviral
      activity triggered by Toll like receptor (TLR)-7 and -9 stimulation. Moreover,
      they are important mediators between innate and adaptive immunity. Although
      nowadays there is available an effective therapeutic arsenal against hepatitis C
      virus (HCV), a protective vaccine is not available. We have analyzed the pDCs
      response to HCV infection in a HCV-Huh7.5 virus-cell system, which allows
      completing the virus infectious cycle. pDCs were cocultured following human
      immunodeficiency virus (HIV) aldrithiol-2 inactivated (AT-2) (TLR-7 agonist) and
      CpG (TLR-9 agonist) stimulation. We employed three virus derivatives, a wild type
      Jc1, an interferon-resistant virus IR, and a high replicative fitness virus P100,
      in order to explore additional IFN-alpha-related virus inhibition mechanisms.
      pDCs inhibited HCV infectivity and replication, and produced IFN-alpha. After TLR
      7 and TLR-9 stimulation, inhibition of infectivity and IFN-alpha production by
      pDCs were enhanced. TLR-7 stimulation drove a higher TNF-related apoptosis
      inducing ligand (TRAIL) expression in pDCs. Additionally, TLR-7 and TLR-9
      stimulated pDCs exhibited a mature phenotype, improving the antigen presentation
      and lymph node homing related markers. In conclusion, pDCs could serve as a drug
      target against HCV in order to improve antiviral activity and as an enhancer of
      viral immunization.IMPORTANCE We implemented a coculture system of pDCs with HCV
      infected hepatoma cell line, Huh7.5. We used three HCV derivatives in order to
      gain insight into pDCs behavior against HCV and associated antiviral mechanisms.
      The results with this cell coculture system support the capacity of pDCs to
      inhibit HCV replication and infectivity mainly via IFN-alpha, but also through
      additional mechanisms associated with pDC maturation. We provided evidence that
      TLR agonists can enhance antiviral pDCs function and can induce phenotypic
      changes that may facilitate the interplay with other immune cells. These findings
      suggest the possibility of including TLR agonists in the strategies of HCV
      vaccine development.

PMID- 30232186
TI  - NSs Protein of Sandfly Fever Sicilian Phlebovirus Counteracts Interferon (IFN)
      Induction by Masking the DNA-Binding Domain of IFN Regulatory Factor 3.
AB  - Sandfly fever Sicilian virus (SFSV) is one of the most widespread and frequently
      identified members of the genus Phlebovirus (order Bunyavirales, family
      Phenuiviridae) infecting humans. Being transmitted by Phlebotomus sandflies, SFSV
      causes a self-limiting, acute, often incapacitating febrile disease ("sandfly
      fever," "Pappataci fever," or "dog disease") that has been known since at least
      the beginning of the 20th century. We show that, similarly to other pathogenic
      phleboviruses, SFSV suppresses the induction of the antiviral type I interferon
      (IFN) system in an NSs-dependent manner. SFSV NSs interfered with the TBK1
      interferon regulatory factor 3 (IRF3) branch of the RIG-I signaling pathway but
      not with NF-kappaB activation. Consistently, we identified IRF3 as a host
      interactor of SFSV NSs. In contrast to IRF3, neither the IFN master regulator
      IRF7 nor any of the related transcription factors IRF2, IRF5, and IRF9 were bound
      by SFSV NSs. In spite of this specificity for IRF3, NSs did not inhibit its
      phosphorylation, dimerization, or nuclear accumulation, and the interaction was
      independent of the IRF3 activation or multimerization state. In further studies,
      we identified the DNA-binding domain of IRF3 (amino acids 1 to 113) as sufficient
      for NSs binding and found that SFSV NSs prevented the association of activated
      IRF3 with the IFN-beta promoter. Thus, unlike highly virulent phleboviruses,
      which either destroy antiviral host factors or sequester whole signaling chains
      into inactive aggregates, SFSV modulates type I IFN induction by directly masking
      the DNA-binding domain of IRF3.IMPORTANCE Phleboviruses are receiving increased
      attention due to the constant discovery of new species and the ongoing spread of
      long-known members of the genus. Outbreaks of sandfly fever were reported in the
      19th century, during World War I, and during World War II. Currently, SFSV is
      recognized as one of the most widespread phleboviruses, exhibiting high
      seroprevalence rates in humans and domestic animals and causing a self-limiting
      but incapacitating disease predominantly in immunologically naive troops and
      travelers. We show how the nonstructural NSs protein of SFSV counteracts the
      upregulation of the antiviral interferon (IFN) system. SFSV NSs specifically
      inhibits promoter binding by IFN transcription factor 3 (IRF3), a molecular
      strategy which is unique among phleboviruses and, to our knowledge, among human
      pathogenic RNA viruses in general. This IRF3-specific and stoichiometric
      mechanism, greatly distinct from the ones exhibited by the highly virulent
      phleboviruses, correlates with the intermediate level of pathogenicity of SFSV.

PMID- 30232188
TI  - Host Enzymes Heparanase and Cathepsin L Promote Herpes Simplex Virus 2 Release
      from Cells.
AB  - Herpes simplex virus 2 (HSV-2) can productively infect many different cell types
      of human and nonhuman origin. Here we demonstrate interconnected roles for two
      host enzymes, heparanase (HPSE) and cathepsin L, in HSV-2 release from cells. In
      vaginal epithelial cells, HSV-2 causes heparan sulfate shedding and upregulation
      in HPSE levels during the productive phase of infection. We also noted increased
      levels of cathepsin L and show that regulation of HPSE by cathepsin L via
      cleavage of HPSE proenzyme is important for infection. Furthermore, inhibition of
      HPSE by a specific inhibitor, OGT 2115, dramatically reduces HSV-2 release from
      vaginal epithelial cells. Likewise, we show evidence that the inhibition of
      cathepsin L is detrimental to the infection. The HPSE increase after infection is
      mediated by an increased NF-kappaB nuclear localization and a resultant
      activation of HPSE transcription. Together these mechanisms contribute to the
      removal of heparan sulfate from the cell surface and thus facilitate virus
      release from cells.IMPORTANCE Genital infections by HSV-2 represent one of the
      most common sexually transmitted viral infections. The virus causes painful
      lesions and sores around the genitals or rectum. Intermittent release of the
      virus from infected tissues during sexual activities is the most common cause of
      transmission. At the molecular level, cell surface heparan sulfate (HS) is known
      to provide attachment sites for HSV-2. While the removal of HS during HSV-1
      release has been shown, not much is known about the host factors and their
      regulators that contribute to HSV-2 release from natural target cell types. Here
      we suggest a role for the host enzyme heparanase in HSV-2 release. Our work
      reveals that in addition to the regulation of transcription by NF-kappaB, HPSE is
      also regulated posttranslationally by cathepsin L and that inhibition of
      heparanase activity directly affects HSV-2 release. We provide unique insights
      into the host mechanisms controlling HSV-2 egress and spread.

PMID- 30232189
TI  - Sindbis Virus Infection Causes Cell Death by nsP2-Induced Transcriptional Shutoff
      or by nsP3-Dependent Translational Shutoff.
AB  - Sindbis virus (SINV) is a representative member of the Alphavirus genus in the
      Togaviridae family. The hallmark of SINV replication in vertebrate cells is a
      rapid development of the cytopathic effect (CPE), which usually occurs within 24
      h postinfection. Mechanistic understanding of CPE might lead to development of
      new prophylactic vaccines and therapeutic means against alphavirus infections.
      However, development of noncytopathic SINV variants and those of other Old World
      alphaviruses was always highly inefficient and usually resulted in selection of
      mutants demonstrating poor replication of the viral genome and transcription of
      subgenomic RNA. This likely caused a nonspecific negative effect on the rates of
      CPE development. The results of this study demonstrate that CPE induced by SINV
      and likely by other Old World alphaviruses is a multicomponent process, in which
      transcriptional and translational shutoffs are the key contributors. Inhibition
      of cellular transcription and translation is determined by SINV nsP2 and nsP3
      proteins, respectively. Defined mutations in the nsP2-specific peptide between
      amino acids (aa) 674 and 688 prevent virus-induced degradation of the catalytic
      subunit of cellular-DNA-dependent RNA polymerase II and transcription inhibition
      and make SINV a strong type I interferon (IFN) inducer without affecting its
      replication rates. Mutations in the nsP3 macrodomain, which were demonstrated to
      inhibit its mono-ADP-ribosylhydrolase activity, downregulate the second component
      of CPE development, inhibition of cellular translation, and also have no effect
      on virus replication rates. Only the combination of nsP2- and nsP3-specific
      mutations in the SINV genome has a dramatic negative effect on the ability of
      virus to induce CPE.IMPORTANCE Alphaviruses are a group of important human and
      animal pathogens with worldwide distribution. Their characteristic feature is a
      highly cytopathic phenotype in cells of vertebrate origin. The molecular
      mechanism of CPE remains poorly understood. In this study, by using Sindbis virus
      (SINV) as a model of the Old World alphaviruses, we demonstrated that SINV
      specific CPE is redundantly determined by viral nsP2 and nsP3 proteins. NsP2
      induces the global transcriptional shutoff, and this nuclear function can be
      abolished by the mutations of the small, surface-exposed peptide in the nsP2
      protease domain. NsP3, in turn, determines the development of translational
      shutoff, and this activity depends on nsP3 macrodomain-associated mono-ADP
      ribosylhydrolase activity. A combination of defined mutations in nsP2 and nsP3,
      which abolish SINV-induced transcription and translation inhibition, in the same
      viral genome does not affect SINV replication rates but makes it noncytopathic
      and a potent inducer of type I interferon.

PMID- 30232190
TI  - Characterization of Antibody Interactions with the G Protein of Vesicular
      Stomatitis Virus Indiana Strain and Other Vesiculovirus G Proteins.
AB  - Vesicular stomatitis virus Indiana strain G protein (VSVind.G) is the most
      commonly used envelope glycoprotein to pseudotype lentiviral vectors (LV) for
      experimental and clinical applications. Recently, G proteins derived from other
      vesiculoviruses (VesG), for example, Cocal virus, have been proposed as
      alternative LV envelopes with possible advantages over VSVind.G. Well
      characterized antibodies that recognize VesG will be useful for vesiculovirus
      research, development of G protein-containing advanced therapy medicinal products
      (ATMPs), and deployment of VSVind-based vaccine vectors. Here, we show that one
      commercially available monoclonal antibody, 8G5F11, binds to and neutralizes G
      proteins from three strains of VSV, as well as Cocal and Maraba viruses, whereas
      the other commercially available monoclonal anti-VSVind.G antibody, IE9F9, binds
      to and neutralizes only VSVind.G. Using a combination of G protein chimeras and
      site-directed mutations, we mapped the binding epitopes of IE9F9 and 8G5F11 on
      VSVind.G. IE9F9 binds close to the receptor binding site and competes with
      soluble low-density lipoprotein receptor (LDLR) for binding to VSVind.G,
      explaining its mechanism of neutralization. In contrast, 8G5F11 binds close to a
      region known to undergo conformational changes when the G protein moves to its
      postfusion structure, and we propose that 8G5F11 cross-neutralizes VesGs by
      inhibiting this.IMPORTANCE VSVind.G is currently regarded as the gold-standard
      envelope glycoprotein to pseudotype lentiviral vectors. However, recently other G
      proteins derived from vesiculoviruses have been proposed as alternative
      envelopes. Here, we investigated two commercially available anti-VSVind.G
      monoclonal antibodies for their ability to cross-react with other vesiculovirus G
      proteins, identified the epitopes they recognize, and explored their
      neutralization activity. We have identified 8G5F11, for the first time, as a
      cross-neutralizing antibody against several vesiculovirus G proteins.
      Furthermore, we elucidated the two different neutralization mechanisms employed
      by these two monoclonal antibodies. Understanding how cross-neutralizing
      antibodies interact with other G proteins may be of interest in the context of
      host-pathogen interaction and coevolution, as well as providing the opportunity
      to modify the G proteins and improve G protein-containing medicinal products and
      vaccine vectors.

PMID- 30232192
TI  - Clinical trials in children and adolescents with systemic lupus erythematosus:
      methodological aspects, regulatory landscape and future opportunities.
AB  - Childhood-onset systemic lupus erythematosus (cSLE) is rare in many regions of
      the world, including Europe. Access to approved medications for cSLE is currently
      limited, among others, due to a lack of high-quality evidence from clinical
      trials. The objectives of the study were to evaluate the current regulatory
      framework regarding medication approvals, delineate barriers to clinical trial
      conduct, and strategies to improve access to new medications for cSLE. Relevant
      methodological and regulatory aspects, epidemiological data, study designs and
      outcome measures are reviewed, and the results of a survey among Paediatric
      Rheumatology International Trials Organisation/Pediatric Rheumatology
      Collaborative Study Group investigators are presented. Laws and regulations in
      the USA and Europe necessitate that novel medicines are studied in paediatric
      populations, if similar or the same diseases in adults have been found to benefit
      from them. Regulatory agencies consider cSLE the paediatric form of SLE in
      adults. For medicines that have been found safe and effective in adult SLE,
      paediatric extrapolation strategies can limit the number and complexity of
      studies needed to support the labelling of these medicines for use in cSLE. In
      this setting, specialised research networks, validated outcome measures,
      stakeholder input, study designs as well as statistical methods successfully used
      in other uncommon diseases will help improve study efficiency in an effort to
      enhance the speed with which new drugs for cSLE can be studied. Open-label
      pharmacokinetic-pharmacodynamic studies are preferred by paediatric
      rheumatologists over double-blind parallel designs for cSLE trials. Appropriate
      infrastructure, outcome measures and sufficient numbers of patients are available
      for the testing of new medicines for children with cSLE.

PMID- 30232193
TI  - Significant joint-destructive association of HLA-DRB1*04:05 independent of DAS28
      in rheumatoid arthritis.

PMID- 30232191
TI  - Natural Secretory Immunoglobulins Promote Enteric Viral Infections.
AB  - Noroviruses are enteric pathogens causing significant morbidity, mortality and
      economic losses worldwide. Secretory immunoglobulins (SIg) are a first line of
      mucosal defense against enteric pathogens. They are secreted into the intestinal
      lumen via the polymeric immunoglobulin receptor (pIgR), where they bind to
      antigens. However, whether natural SIg protect against norovirus infection
      remains unknown. To determine if natural SIg alter murine norovirus (MNV)
      pathogenesis, we infected pIgR knockout (KO) mice, which lack SIg in mucosal
      secretions. Acute MNV infection was significantly reduced in pIgR KO mice
      compared to controls, despite increased MNV target cells in the Peyer's patch.
      Natural SIg did not alter MNV binding to, or crossing, of the follicle-associated
      epithelium (FAE) into the lymphoid follicle. Instead, naive pIgR KO mice have
      enhanced levels of the antiviral inflammatory molecules interferon gamma
      (IFNgamma) and inducible nitric oxide synthase (iNOS) in the ileum compared to
      controls. Strikingly, depletion of the intestinal microbiota in pIgR KO and
      control mice resulted in comparable IFNgamma and iNOS levels, as well as MNV
      infectious titers. IFNgamma treatment of WT mice and neutralization of IFNgamma
      in pIgR KO mice reduced MNV titers, implicating this antiviral cytokine in the
      phenotype. Reduced gastrointestinal infection in pIgR KO mice was also observed
      with another enteric virus, reovirus. Collectively, our findings suggest that
      natural SIg are not protective during enteric virus infection, but rather that
      SIg promote enteric viral infection through alterations in microbial immune
      responses.

PMID- 30232194
TI  - Two distinct clinical phenotypes of pulmonary arterial hypertension secondary to
      systemic lupus erythematosus.

PMID- 30232195
TI  - Physiological electric field works via the VEGF receptor to stimulate neovessel
      formation of vascular endothelial cells in a 3D environment.
AB  - Electrical stimulation induces significant neovessel formation in vivo We have
      shown that electrical stimulation of endothelial cells functions as an important
      contributor to angiogenesis in monolayer culture. Because angiogenesis occurs in
      a three-dimensional (3D) environment, in this study we investigated the effects
      of a direct current (DC) electrical field (EF) on endothelial neovessel formation
      in 3D culture. There was a significant increase in tube formation when
      endothelial cells were stimulated with EF for 4 h. The lengths of the tube-like
      structures were augmented further by the continued EF exposure. The lengths of
      the tubes also increased dose-dependently in the EF-treated cultures in the field
      strengths of 50 mV/mm~200 mV/mm for 6 h. Electrical fields of small physiological
      magnitude enhanced VEGF expression by endothelial cells in 3D culture. EF
      treatment also resulted in activation of VEGFR2, Akt, extracellular regulated
      kinase 1,2 (Erk1/2), as well as the c-Jun NH2-terminal kinase (JNK). The tyrosine
      kinase inhibitor SU1498 that blocks VEGFR2 activity exhibited a potent inhibition
      of tube growth, and the Akt inhibitor MK-2206 2HCl, the Erk1/2 inhibitor U0126
      and the JNK inhibitor SB203580 significantly reduced EF-stimulated tubulogenesis.
      These results suggest the importance of the VEGFR2 signaling pathway during EF
      induced angiogenesis. The results of this study provide novel evidence that
      endogenous EFs may promote blood vessel formation of endothelial cells by
      activating the VEGF receptor signaling pathway.

PMID- 30232196
TI  - Targeted genome fragmentation with CRISPR/Cas9 enables fast and efficient
      enrichment of small genomic regions and ultra-accurate sequencing with low DNA
      input (CRISPR-DS).
AB  - Next-generation sequencing methods suffer from low recovery, uneven coverage, and
      false mutations. DNA fragmentation by sonication is a major contributor to these
      problems because it produces randomly sized fragments, PCR amplification bias,
      and end artifacts. In addition, oligonucleotide-based hybridization capture, a
      common target enrichment method, has limited efficiency for small genomic
      regions, contributing to low recovery. This becomes a critical problem in
      clinical applications, which value cost-effective approaches focused on the
      sequencing of small gene panels. To address these issues, we developed a targeted
      genome fragmentation approach based on CRISPR/Cas9 digestion that produces DNA
      fragments of similar length. These fragments can be enriched by a simple size
      selection, resulting in targeted enrichment of up to approximately 49,000-fold.
      Additionally, homogenous length fragments significantly reduce PCR amplification
      bias and maximize read usability. We combined this novel target enrichment
      approach with Duplex Sequencing, which uses double-strand molecular tagging to
      correct for sequencing errors. The approach, termed CRISPR-DS, enables efficient
      target enrichment of small genomic regions, even coverage, ultra-accurate
      sequencing, and reduced DNA input. As proof of principle, we applied CRISPR-DS to
      the sequencing of the exonic regions of TP53 and performed side-by-side
      comparisons with standard Duplex Sequencing. CRISPR-DS detected previously
      reported pathogenic TP53 mutations present as low as 0.1% in peritoneal fluid of
      women with ovarian cancer, while using 10- to 100-fold less DNA than standard
      Duplex Sequencing. Whether used as standalone enrichment or coupled with high
      accuracy sequencing methods, CRISPR-based fragmentation offers a simple solution
      for fast and efficient small target enrichment.

PMID- 30232197
TI  - Deep taxon sampling reveals the evolutionary dynamics of novel gene families in
      Pristionchus nematodes.
AB  - The widespread identification of genes without detectable homology in related
      taxa is a hallmark of genome sequencing projects in animals, together with the
      abundance of gene duplications. Such genes have been called novel, young, taxon
      restricted, or orphans, but little is known about the mechanisms accounting for
      their origin, age, and mode of evolution. Phylogenomic studies relying on deep
      and systematic taxon sampling and using the comparative method can provide
      insight into the evolutionary dynamics acting on novel genes. We used a
      phylogenomic approach for the nematode model organism Pristionchus pacificus and
      sequenced six additional Pristionchus and two outgroup species. This resulted in
      10 genomes with a ladder-like phylogeny, sequenced in one laboratory using the
      same platform and analyzed by the same bioinformatic procedures. Our analysis
      revealed that 68%-81% of genes are assignable to orthologous gene families, the
      majority of which defined nine age classes with presence/absence patterns that
      can be explained by single evolutionary events. Contrasting different age
      classes, we find that older age classes are concentrated at chromosome centers,
      whereas novel gene families preferentially arise at the periphery, are weakly
      expressed, evolve rapidly, and have a high propensity of being lost. Over time,
      they increase in expression and become more constrained. Thus, the detailed
      phylogenetic resolution allowed a comprehensive characterization of the
      evolutionary dynamics of Pristionchus genomes indicating that distribution of age
      classes and their associated differences shape chromosomal divergence. This study
      establishes the Pristionchus system for future research on the mechanisms that
      drive the formation of novel genes.

PMID- 30232198
TI  - Young genes have distinct gene structure, epigenetic profiles, and
      transcriptional regulation.
AB  - Species-specific, new, or "orphan" genes account for 10%-30% of eukaryotic
      genomes. Although initially considered to have limited function, an increasing
      number of orphan genes have been shown to provide important phenotypic
      innovation. How new genes acquire regulatory sequences for proper temporal and
      spatial expression is unknown. Orphan gene regulation may rely in part on
      origination in open chromatin adjacent to preexisting promoters, although this
      has not yet been assessed by genome-wide analysis of chromatin states. Here, we
      combine taxon-rich nematode phylogenies with Iso-Seq, RNA-seq, ChIP-seq, and ATAC
      seq to identify the gene structure and epigenetic signature of orphan genes in
      the satellite model nematode Pristionchus pacificus Consistent with previous
      findings, we find young genes are shorter, contain fewer exons, and are on
      average less strongly expressed than older genes. However, the subset of orphan
      genes that are expressed exhibit distinct chromatin states from similarly
      expressed conserved genes. Orphan gene transcription is determined by a lack of
      repressive histone modifications, confirming long-held hypotheses that open
      chromatin is important for new gene formation. Yet orphan gene start sites more
      closely resemble enhancers defined by H3K4me1, H3K27ac, and ATAC-seq peaks, in
      contrast to conserved genes that exhibit traditional promoters defined by H3K4me3
      and H3K27ac. Although the majority of orphan genes are located on chromosome arms
      that contain high recombination rates and repressive histone marks, strongly
      expressed orphan genes are more randomly distributed. Our results support a model
      of new gene origination by rare integration into open chromatin near enhancers.

PMID- 30232202
TI  - Rare cause of ovarian mass.
AB  - Pelvic actinomycosis is a rare entity that occurs almost exclusively in women,
      the presentation of which is usually non-specific and variable. Pelvic
      actinomycosis is almost always associated with the use of an intrauterine
      contraceptive device (IUD). Pelvic actinomycosis unrelated to IUD use is almost
      always associated with previous surgical procedures. The symptoms, clinical signs
      and radiological findings are usually non-specific, mimicking an ovarian
      malignancy. So an awareness of this rare condition and a proper diagnosis can
      avoid unnecessary surgeries because these cases can be treated with a prolonged
      course of antibiotics. We present a case of pelvic actinomycosis which
      masqueraded as an ovarian malignancy.

PMID- 30232199
TI  - Metagenomic analysis with strain-level resolution reveals fine-scale variation in
      the human pregnancy microbiome.
AB  - Recent studies suggest that the microbiome has an impact on gestational health
      and outcome. However, characterization of the pregnancy-associated microbiome has
      largely relied on 16S rRNA gene amplicon-based surveys. Here, we describe an
      assembly-driven, metagenomics-based, longitudinal study of the vaginal, gut, and
      oral microbiomes in 292 samples from 10 subjects sampled every three weeks
      throughout pregnancy. Nonhuman sequences in the amount of 1.53 Gb were assembled
      into scaffolds, and functional genes were predicted for gene- and pathway-based
      analyses. Vaginal assemblies were binned into 97 draft quality genomes.
      Redundancy analysis (RDA) of microbial community composition at all three body
      sites revealed gestational age to be a significant source of variation in
      patterns of gene abundance. In addition, health complications were associated
      with variation in community functional gene composition in the mouth and gut. The
      diversity of Lactobacillus iners-dominated communities in the vagina, unlike most
      other vaginal community types, significantly increased with gestational age. The
      genomes of co-occurring Gardnerella vaginalis strains with predicted distinct
      functions were recovered in samples from two subjects. In seven subjects, gut
      samples contained strains of the same Lactobacillus species that dominated the
      vaginal community of that same subject and not other Lactobacillus species;
      however, these within-host strains were divergent. CRISPR spacer analysis
      suggested shared phage and plasmid populations across body sites and individuals.
      This work underscores the dynamic behavior of the microbiome during pregnancy and
      suggests the potential importance of understanding the sources of this behavior
      for fetal development and gestational outcome.

PMID- 30232200
TI  - Transient T-bet expression functionally specifies a distinct T follicular helper
      subset.
AB  - T follicular helper (Tfh) cells express transcription factor BCL-6 and cytokine
      IL-21. Mature Tfh cells are also capable of producing IFN-gamma without
      expressing the Th1 transcription factor T-bet. Whether this IFN-gamma-producing
      Tfh population represents a unique Tfh subset with a distinct differentiation
      pathway is poorly understood. By using T-bet fate-mapping mouse strains, we
      discovered that almost all the IFN-gamma-producing Tfh cells have previously
      expressed T-bet and express high levels of NKG2D. DNase I hypersensitivity
      analysis indicated that the Ifng gene locus is partially accessible in this "ex-T
      bet" population with a history of T-bet expression. Furthermore, multicolor
      tissue imaging revealed that the ex-T-bet Tfh cells found in germinal centers
      express IFN-gamma in situ. Finally, we found that IFN-gamma-expressing Tfh cells
      are absent in T-bet-deficient mice, but fully present in mice with T-bet deletion
      at late stages of T cell differentiation. Together, our findings demonstrate that
      transient expression of T-bet epigenetically imprints the Ifng locus for cytokine
      production in this Th1-like Tfh cell subset.

PMID- 30232201
TI  - Positron emission tomography and reframing vasculitis as a spectrum of disease
      when investigating a patient with a fever of unknown origin.
AB  - A retired businessman presented to the infectious diseases department with a
      history of ongoing fevers and myalgia and raised inflammatory markers. This
      continued despite adequate antibiotic treatment of an epididymo-orchitis.
      Extensive investigations, including bone marrow and liver biopsies and a positron
      emission tomography, did not reveal a cause but showed reactive change in the
      bone marrow. Later, he developed a vasculitic rash and vision loss due to non
      arteritic anterior ischaemic optic neuropathy. High-dose steroids were
      immediately initiated. A temporal artery biopsy was performed, which confirmed a
      healing large vessel vasculitis, possibly giant cell arteritis. He has responded
      very well to therapy. We must better appreciate the limitations of positron
      emission tomography in investigating a fever of unknown origin. The case also
      encourages awareness of autoimmune disorders as the leading category of causative
      diseases for this in older age groups.

PMID- 30232203
TI  - 87-year-old woman with improved pulmonary function following accidental long-term
      inhalation therapy with dabigatran.
AB  - Accidental long-term dabigatran etexilate inhalation was associated with
      subtherapeutic dabigatran serum concentrations in an elderly female patient with
      restrictive lung disease. A significant improvement in her pulmonary function was
      noted without other therapy directed towards her bronchopulmonary disease.

PMID- 30232204
TI  - Partial mid-portion Achilles tear resulting in substantial improvement in pain
      and function in an amateur long-distance runner.
AB  - This case presents symptom resolution for a long-distance runner with chronic
      Achilles tendinopathy (AT), following a partial tear of his Achilles tendon. The
      patient reported a sudden pain during a morning run, with preserved function.
      Three hours postinjury, he was reviewed in a musculoskeletal clinic. An
      ultrasound scan confirmed a partial Achilles tear, associated with significant
      Doppler activity. His index of AT severity The Victorian Institute of Sports
      Assessment - Achilles Questionnaire (VISA-A) 4 hours postinjury was markedly
      higher compared with 2 weeks preinjury, indicating reduced symptom severity. A
      follow-up scan 4 weeks postinjury showed minimal mid-portion swelling and no
      signs of the tear. His VISA-A score showed continued symptom improvement. This
      case represents resolution of tendinopathic symptomatology post partial Achilles
      tear. While the natural histories of AT and Achilles tears remain unknown, this
      case may indicate that alongside the known role of loading, inflammation may be a
      secondary mediator central to the successful resolution of AT pain.

PMID- 30232205
TI  - Unusual case of levamisole-induced dual-positive ANCA vasculitis and crescentic
      glomerulonephritis.
AB  - Cocaine adulterated levamisole is an increasingly reported cause of skin
      necrosis, arthralgia and systemic vasculitis, but renal involvement is uncommon.
      We present a case of a 40-year-old Hispanic man with a history of cocaine abuse
      who presented with acute kidney injury to the rheumatology clinic where he was
      being treated for chronic inflammatory arthritis. He was found to have a serum
      creatinine of 2.5 mg/dL, microscopic haematuria and subnephrotic proteinuria,
      along with positive proteinase 3, myeloperoxidase, anticardiolipin antibodies and
      an elevated antinuclear antibody titre. The renal pathology revealed focal
      necrotising glomerulonephritis with crescentic features and mild immune type
      deposition. The patient was treated with cocaine abstinence, pulse dose steroids
      followed by maintenance prednisone, rituximab and cyclophosphamide. His renal
      function subsequently improved but did not normalise. We believe that his
      incomplete improvement was due to the degree of kidney injury on presentation as
      well as recidivism with cocaine use.

PMID- 30232206
TI  - Microangiopathic haemolytic anaemia with thrombocytopenia induced by vitamin B12
      deficiency long term after gastrectomy.
AB  - Microangiopathic haemolytic anaemia with thrombocytopenia, called pseudo
      thrombotic microangiopathy (TMA), is a clinically important complication in
      patients with vitamin B12 deficiency. We herein present a case of an 80-year-old
      woman with pseudo-TMA after gastrectomy. She was initially suspected with
      thrombotic thrombocytopenic purpura based on rapid progression of anaemia with
      schistocytes and thrombocytopenia; however, her anaemia and thrombocytopenia were
      improved by vitamin B12 supplementation alone, with a single session of plasma
      exchange. Vitamin B12 deficiency was finally confirmed by low vitamin B12 levels
      from the patient's initial blood sample. In addition, normal ADAMTS13 activity
      was proven, lowering the likelihood of thrombotic thrombocytopenic purpura.
      Therefore, this patient was diagnosed with pseudo-TMA caused by vitamin B12
      deficiency. Pseudo-TMA can occur in patients with vitamin B12 deficiency post
      gastrectomy.

PMID- 30232207
TI  - Herpes simplex virus keratitis mimicking Acanthamoeba keratitis: a
      clinicopathological correlation.
AB  - A 36-year-old male, soft contact lens wearer was referred by his primary
      ophthalmologist for corneal ulcer of the right eye (OD), which was persistent
      despite topical fluoroquinolone therapy for 1 month. A ring-shaped infiltrate
      typically seen in Acanthamoeba infection was noted, and topical therapy with
      chlorhexidine and polyhexamethylene biguanide was initiated. However, the
      patient's condition deteriorated over the next several weeks; thus, diagnostic
      and therapeutic penetrating keratoplasty was performed. The postoperative
      immunohistochemical analysis suggested a diagnosis of herpes simplex virus (HSV)
      keratitis. The patient ultimately improved after initiation of oral valacyclovir
      following penetrating keratoplasty. We report a case of a commonly encountered
      clinical entity, HSV keratitis, with an atypical clinical presentation,
      masquerading as Acanthamoeba keratitis.

PMID- 30232210
TI  - Giant craniopharyngioma in an adult presenting with new onset seizure.

PMID- 30232208
TI  - Acute testicular pain secondary to a leaking abdominal aortic aneurysm (AAA).
AB  - We present the case of a 56-year-old male smoker with a background of
      hypertension who presented with acute onset right testicular pain secondary to a
      leaking abdominal aortic aneurysm. Following urgent surgical repair and a
      complicated intensive care recovery, the patient was discharged with no residual
      disability. This case highlights an atypical presentation of what is a
      devastating illness.

PMID- 30232209
TI  - Isolated Fournier's gangrene of the penis with penile autoamputation.

PMID- 30232211
TI  - Reduced GLP-1 Secretion at 30 Minutes After a 75-g Oral Glucose Load Is Observed
      in Gestational Diabetes Mellitus: A Prospective Cohort Study.
AB  - Glucagon-like peptide 1 (GLP-1) levels may be reduced in type 2 diabetes, but
      whether a similar impairment exists in gestational diabetes mellitus (GDM) has
      not been established. We studied this in a prospective cohort study of pregnant
      women (n = 144) during oral glucose tolerance test (OGTT). GLP-1, glucose, and
      insulin were sampled at 30-min intervals during a 2-h 75-g OGTT, and indices of
      insulin secretion and sensitivity were calculated. In a nested case-control
      study, women with GDM (n = 19) had 12% lower total GLP-1 secretion area under the
      curve (AUC) compared with control subjects matched for age, ethnicity, and
      gestational age (n = 19), selected from within the lowest quartile of glucose120
      min values in our cohort. GDM had lower GLP-1 response in the first 30 min (19%
      lower GLP-130 min and 17% lower AUC0-30 min) after adjustment for possible
      confounders. Their glucose levels began to diverge at 30 min of the OGTT with
      increasing insulin levels, and by 120 min, their insulin levels were three times
      higher. In a secondary cohort of 57 women that included "high-normal" glucose120
      min values, low GLP-1 AUC0-30 min was independently associated with lower indices
      of insulin secretion and sensitivity. In conclusion, we have observed that women
      with GDM have lower GLP-1 response at 30 min of an OGTT and hyperglycemia at 120
      min despite significant hyperinsulinemia.

PMID- 30232212
TI  - Methodological difficulties of studying alcohol consumption and dementia.

PMID- 30232213
TI  - Introducing the Journal of Clinical Pathology Grand Rounds: a new
      multidisciplinary clinical pathology forum.

PMID- 30232215
TI  - Contrasting effects of sterols on metabolism.

PMID- 30232214
TI  - Two-year-old girl with tuberous xanthomas.

PMID- 30232216
TI  - Sitosterolaemia: a rare cause of accelerated atherosclerosis.

PMID- 30232217
TI  - Modes of Death Within a Children's Hospital.
AB  - : : media-1vid110.1542/5804909711001PEDS-VA_2017-4182Video Abstract BACKGROUND:
      Knowledge about how children die in pediatric hospitals is limited, and this
      hinders improvement in hospital-based end-of-life care. METHODS: We conducted a
      retrospective chart review of all the patients who died in a children's hospital
      between July 2011 and June 2014, collecting demographic and diagnostic
      information, hospital length of stay, location of death, and palliative care
      consultation. A qualitative review of provider notes and resuscitation records
      was used to create 5 mutually exclusive modes of death, which were then assigned
      to each patient. Analysis included the calculation of descriptive statistics and
      multinomial logistic regression modeling. RESULTS: We identified 579 patients who
      were deceased; 61% were <1 year of age. The ICU was the most common location of
      death (NICU 29.7%; PICU 27.8%; cardiac ICU 16.6%). Among the 5 modes of death,
      the most common was the withdrawal of life-sustaining technology (40.2%),
      followed by nonescalation (25.6%), failed resuscitation (22.8%), code then
      withdrawal (6.0%), and death by neurologic criteria (5.3%). After adjustment,
      patients who received a palliative care consultation were less likely to
      experience a code death (odds ratio 0.31; 95% confidence interval 0.13-0.75),
      although African American patients were more likely than white patients to
      experience a code death (odds ratio 2.46; 95% confidence interval 1.05-5.73),
      mostly because of code events occurring in the first 24 hours of hospitalization.
      CONCLUSIONS: Most deaths in a children's hospital occur in ICUs after the
      withdrawal of life-sustaining technology. Race and palliative care involvement
      may influence the manner of a child's death.

PMID- 30232218
TI  - Child Mortality in the United States: Bridging Palliative Care and Public Health
      Perspectives.

PMID- 30232219
TI  - CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer
      Datasets.
AB  - With the advent of OMICs technologies, both individual research groups and
      consortia have spear-headed the characterization of human samples of multiple
      pathophysiologic origins, resulting in thousands of archived genomes and
      transcriptomes. Although a variety of web tools are now available to extract
      information from OMICs data, their utility has been limited by the capacity of
      nonbioinformatician researchers to exploit the information. To address this
      problem, we have developed CANCERTOOL, a web-based interface that aims to
      overcome the major limitations of public transcriptomics dataset analysis for
      highly prevalent types of cancer (breast, prostate, lung, and colorectal).
      CANCERTOOL provides rapid and comprehensive visualization of gene expression data
      for the gene(s) of interest in well-annotated cancer datasets. This visualization
      is accompanied by generation of reports customized to the interest of the
      researcher (e.g., editable figures, detailed statistical analyses, and access to
      raw data for reanalysis). It also carries out gene-to-gene correlations in
      multiple datasets at the same time or using preset patient groups. Finally, this
      new tool solves the time-consuming task of performing functional enrichment
      analysis with gene sets of interest using up to 11 different databases at the
      same time. Collectively, CANCERTOOL represents a simple and freely accessible
      interface to interrogate well-annotated datasets and obtain publishable
      representations that can contribute to refinement and guidance of cancer-related
      investigations at all levels of hypotheses and design.Significance: In order to
      facilitate access of research groups without bioinformatics support to public
      transcriptomics data, we have developed a free online tool with an easy-to-use
      interface that allows researchers to obtain quality information in a readily
      publishable format. Cancer Res; 78(21); 6320-8. (c)2018 AACR.

PMID- 30232220
TI  - Heterozygosity of Chaperone Grp78 Reduces Intestinal Stem Cell Regeneration
      Potential and Protects against Adenoma Formation.
AB  - Deletion of endoplasmic reticulum resident chaperone Grp78 results in activation
      of the unfolded protein response and causes rapid depletion of the entire
      intestinal epithelium. Whether modest reduction of Grp78 may affect stem cell
      fate without compromising intestinal integrity remains unknown. Here, we employ a
      model of epithelial-specific, heterozygous Grp78 deletion by use of VillinCreERT2
      Rosa26ZsGreen/LacZ-Grp78+/fl mice and organoids. We examine models of irradiation
      and tumorigenesis, both in vitro and in vivo Although we observed no phenotypic
      changes in Grp78 heterozygous mice, Grp78 heterozygous organoid growth was
      markedly reduced. Irradiation of Grp78 heterozygous mice resulted in less
      frequent regeneration of crypts compared with nonrecombined (wild-type) mice,
      exposing reduced capacity for self-renewal upon genotoxic insult. We crossed mice
      to Apc-mutant animals for adenoma studies and found that adenomagenesis in Apc
      heterozygous-Grp78 heterozygous mice was reduced compared with Apc heterozygous
      controls (1.43 vs. 3.33; P < 0.01). In conclusion, epithelium-specific Grp78
      heterozygosity compromises epithelial fitness under conditions requiring
      expansive growth such as adenomagenesis or regeneration after gamma-irradiation.
      These results suggest that Grp78 may be a therapeutic target in prevention of
      intestinal neoplasms without affecting normal tissue.Significance: Heterozygous
      disruption of chaperone protein Grp78 reduces tissue regeneration and expansive
      growth and protects from tumor formation without affecting intestinal
      homeostasis. Cancer Res; 78(21); 6098-106. (c)2018 AACR.

PMID- 30232222
TI  - Reduced CD160 Expression Contributes to Impaired NK-cell Function and Poor
      Clinical Outcomes in Patients with HCC.
AB  - : We previously reported that deficiencies in natural killer (NK)-cell number and
      function play an important role in the progression of hepatocellular carcinoma
      (HCC). However, the mechanisms underlying this phenomenon remain obscure. In this
      study, we analyzed the expression of CD160 on intrahepatic NK cells by evaluating
      peritumoral and intratumoral tissues of 279 patients with HCC and 20 healthy
      livers. We observed reduced expression of CD160 on intratumoral NK cells, and
      patients with lower CD160 cell densities within tumor cells exhibited worse
      disease and a higher recurrence rate. High-resolution microarray and gene set
      enrichment analysis of flow cytometry-sorted primary intrahepatic CD160+ and
      CD160- NK cells of healthy livers indicated that human CD160+ NK cells exhibited
      functional activation, high IFNgamma production, and NK-mediated immunity. In
      addition, global transcriptomic analysis of sorted peritumoral and intratumoral
      CD160+ NK cells revealed that intratumoral CD160+ NK cells are more exhausted
      than peritumoral CD160+ NK cells and produce less IFNgamma. High levels of
      TGFbeta1 interfered with production of IFNgamma by CD160+ NK cells, blocking of
      which specifically restored IFNgamma production in CD160+ NK cells to normal
      levels. These findings indicate that reduced numbers of CD160+ NK cells, together
      with the functional impairment of CD160+ NK cells by TGFbeta1, contribute to
      tumor immune escape. In addition, restoring the expression of CD160 and blocking
      TGFbeta1 appear a promising therapeutic strategy against liver cancer.
      SIGNIFICANCE: These findings show that reduced number and function of CD160+ NK
      cells in the tumor microenvironment contributes to immune escape of HCC; blocking
      TGFbeta1 restores IFNgamma production of CD160+ NK cells.Graphical Abstract:
      http://cancerres.aacrjournals.org/content/canres/78/23/6581/F1.large.jpg.

PMID- 30232221
TI  - Tobacco Carcinogen-Induced Production of GM-CSF Activates CREB to Promote
      Pancreatic Cancer.
AB  - Although smoking is a significant risk factor for pancreatic ductal
      adenocarcinoma (PDAC), the molecular mechanisms underlying PDAC development and
      progression in smokers are still unclear. Here, we show the role of cyclic AMP
      response element-binding protein (CREB) in the pathogenesis of smoking-induced
      PDAC. Smokers had significantly higher levels of activated CREB when compared
      with nonsmokers. Cell lines derived from normal pancreas and pancreatic
      intraepithelial neoplasm (PanIN) exhibited low baseline pCREB levels compared
      with PDAC cell lines. Furthermore, elevated CREB expression correlated with
      reduced survival in patients with PDAC. Depletion of CREB significantly reduced
      tumor burden after tobacco-specific nitrosamine 4-(methyl nitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) treatment, suggesting a CREB-dependent contribution to
      PDAC growth and progression in smokers. Conversely, NNK accelerated PanIN lesion
      and PDAC formation via GM-CSF-mediated activation of CREB in a PDAC mouse model.
      CREB inhibition (CREBi) in mice more effectively reduced primary tumor burden
      compared with control or GM-CSF blockade alone following NNK exposure. GM-CSF
      played a role in the recruitment of tumor-associated macrophages (TAM) and
      regulatory T cell (Treg) expansion and promotion, whereas CREBi significantly
      reduced TAM and Treg populations in NNK-exposed mice. Overall, these results
      suggest that NNK exposure leads to activation of CREB through GM-CSF, promoting
      inflammatory and Akt pathways. Direct inhibition of CREB, but not GM-CSF,
      effectively abrogates these effects and inhibits tumor progression, offering a
      viable therapeutic strategy for patients with PDAC.Significance: These findings
      identify GM-CSF-induced CREB as a driver of pancreatic cancer in smokers and
      demonstrate the therapeutic potential of targeting CREB to reduce PDAC tumor
      growth.Graphical Abstract:
      http://cancerres.aacrjournals.org/content/canres/78/21/6146/F1.large.jpg Cancer
      Res; 78(21); 6146-58. (c)2018 AACR.

PMID- 30232223
TI  - Neural Deletion of Glucose Transporter Isoform 3 Creates Distinct Postnatal and
      Adult Neurobehavioral Phenotypes.
AB  - We created a neural-specific conditional murine glut3 (Slc2A3) deletion (glut3
      flox/flox/nestin-Cre+) to examine the effect of a lack of Glut3 on
      neurodevelopment. Compared with age-matched glut3 flox/flox = WT and
      heterozygotes (glut3 flox/+/nestin-Cre+), we found that a >90% reduction in male
      and female brain Glut3 occurred by postnatal day 15 (PN15) in glut3
      flox/flox/nestin-Cre+ This genetic manipulation caused a diminution in brain
      weight and cortical thickness at PN15, a reduced number of dendritic spines, and
      fewer ultrasonic vocalizations. Patch-clamp recordings of cortical pyramidal
      neurons revealed increased frequency of bicuculline-induced paroxysmal discharges
      as well as reduced latency, attesting to a functional synaptic and cortical
      hyperexcitability. Concomitant stunting with lower glucose concentrations despite
      increased milk intake shortened the lifespan, failing rescue by a ketogenic diet.
      This led to creating glut3 flox/flox/CaMK2alpha-Cre+ mice lacking Glut3 in the
      adult male limbic system. These mice had normal lifespan, displayed reduced IPSCs
      in cortical pyramidal neurons, less anxiety/fear, and lowered spatial memory and
      motor abilities but heightened exploratory and social responses. These distinct
      postnatal and adult phenotypes, based upon whether glut3 gene is globally or
      restrictively absent, have implications for humans who carry copy number
      variations and present with neurodevelopmental disorders.SIGNIFICANCE STATEMENT
      Lack of the key brain-specific glucose transporter 3 gene found in neurons during
      early postnatal life results in significant stunting, a reduction in dendritic
      spines found on neuronal processes and brain size, heightened neuronal
      excitability, along with a shortened lifespan. When occurring in the adult and
      limited to the limbic system alone, lack of this gene in neurons reduces the fear
      of spatial exploration and socialization but does not affect the lifespan. These
      features are distinct heralding differences between postnatal and adult
      phenotypes based upon whether the same gene is globally or restrictively lacking.
      These findings have implications for humans who carry copy number variations
      pertinent to this gene and have been described to present with neurodevelopmental
      disorders.

PMID- 30232225
TI  - Activated Natural Killer Cells in Combination with Anti-GD2 Antibody Dinutuximab
      Improve Survival of Mice after Surgical Resection of Primary Neuroblastoma.
AB  - Purpose: Immunotherapy of neuroblastoma that remains after myeloablative
      chemotherapy with anti-GD2 antibody dinutuximab has increased the two-year event
      free and overall survival of high-risk neuroblastoma patients; however, 40% of
      patients develop recurrent disease during or after this treatment. To determine
      the potential of such antibody-based immunotherapy earlier in treatment, a mouse
      model was developed in which surgical resection of the primary tumor was followed
      by therapy of residual disease with dinutuximab combined with ex vivo-activated
      human natural killer (aNK) cells.Experimental Design: The effect of combining
      dinutuximab with human aNK cells was determined in vitro with cellular
      cytotoxicity and Matrigel invasion assays. The in vivo efficacy of dinutuximab
      and aNK cells against neuroblastoma was assessed following resection of primary
      tumors formed by two cell lines or a patient-derived xenograft (PDX) in
      immunodeficient NOD-scid gamma mice.Results: In vitro, the combination of aNK
      cells and dinutuximab caused cytotoxicity and decreased invasiveness of three
      human neuroblastoma cell lines. Treatment of mice with dinutuximab combined with
      aNK cells after surgical resection of primary intrarenal tumors formed by two
      cell lines or a PDX decreased tumor cells in liver and bone marrow as evaluated
      by histopathology and bioluminescence imaging. Survival of mice after resection
      of these tumors was most significantly increased by treatment with dinutuximab
      combined with aNK cells compared with that of untreated mice.Conclusions: The
      combination of dinutuximab and adoptively transferred human aNK cells following
      surgical resection of primary neuroblastomas significantly improves survival of
      immunodeficient mice. Clin Cancer Res; 1-9. (c)2018 AACR.

PMID- 30232224
TI  - A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with
      Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers.
AB  - Purpose: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of
      prostate cancer that may develop de novo or as a mechanism of treatment
      resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the
      interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc
      signaling, and suppressing tumor growth.Experimental Design: Sixty men were
      treated with alisertib 50 mg twice daily for 7 days every 21 days. Eligibility
      included metastatic prostate cancer and at least one: small-cell neuroendocrine
      morphology; >=50% neuroendocrine marker expression; new liver metastases without
      PSA progression; or elevated serum neuroendocrine markers. The primary endpoint
      was 6-month radiographic progression-free survival (rPFS). Pretreatment biopsies
      were evaluated by whole exome and RNA-seq and patient-derived organoids were
      developed.Results: Median PSA was 1.13 ng/mL (0.01-514.2), number of prior
      therapies was 3, and 68% had visceral metastases. Genomic alterations involved
      RB1 (55%), TP53 (46%), PTEN (29%), BRCA2 (29%), and AR (27%), and there was a
      range of androgen receptor signaling and NEPC marker expression. Six-month rPFS
      was 13.4% and median overall survival was 9.5 months (7.3-13). Exceptional
      responders were identified, including complete resolution of liver metastases and
      prolonged stable disease, with tumors suggestive of N-myc and Aurora-A
      overactivity. Patient organoids exhibited concordant responses to alisertib and
      allowed for the dynamic testing of Aurora-N-myc complex disruption.Conclusions:
      Although the study did not meet its primary endpoint, a subset of patients with
      advanced prostate cancer and molecular features supporting Aurora-A and N-myc
      activation achieved significant clinical benefit from single-agent alisertib.
      Clin Cancer Res; 1-9. (c)2018 AACR.

PMID- 30232226
TI  - Arginine deficiency is involved in thrombocytopenia and immunosuppression in
      severe fever with thrombocytopenia syndrome.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) caused by a recently
      identified bunyavirus, SFTSV, is an emerging infectious disease with extensive
      geographical distribution and high mortality. Progressive viral replication and
      severe thrombocytopenia are key features of SFTSV infection and fatal outcome,
      whereas the underlying mechanisms are unknown. We revealed arginine deficiency in
      SFTS cases by performing metabolomics analysis on two independent patient
      cohorts, suggesting that arginine metabolism by nitric oxide synthase and
      arginase is a key pathway in SFTSV infection and consequential death. Arginine
      deficiency was associated with decreased intraplatelet nitric oxide (Plt-NO)
      concentration, platelet activation, and thrombocytopenia. An expansion of
      arginase-expressing granulocytic myeloid-derived suppressor cells was observed,
      which was related to T cell CD3-zeta chain down-regulation and virus clearance
      disturbance, implicating a role of arginase activity and arginine depletion in
      the impaired anti-SFTSV T cell function. Moreover, a comprehensive measurement of
      arginine bioavailability, global arginine bioavailability ratio, was shown to be
      a good prognostic marker for fatal prediction in early infection. A randomized
      controlled trial demonstrated that arginine administration was correlated with
      enhanced Plt-NO concentration, suppressed platelet activation, and elevated CD3
      zeta chain expression and eventually associated with an accelerated virus
      clearance and thrombocytopenia recovery. Together, our findings revealed the
      arginine catabolism pathway-associated regulation of platelet homeostasis and T
      cell dysregulation after SFTSV infection, which not only provided a functional
      mechanism underlying SFTS pathogenesis but also offered an alternative therapy
      choice for SFTS.

PMID- 30232227
TI  - Axonal organization defects in the hippocampus of adult conditional BACE1
      knockout mice.
AB  - beta-Site APP (amyloid precursor protein) cleaving enzyme 1 (BACE1) is the beta
      secretase enzyme that initiates production of the toxic amyloid-beta peptide that
      accumulates in the brains of patients with Alzheimer's disease (AD). Hence, BACE1
      is a prime therapeutic target, and several BACE1 inhibitor drugs are currently
      being tested in clinical trials for AD. However, the safety of BACE1 inhibition
      is unclear. Germline BACE1 knockout mice have multiple neurological phenotypes,
      although these could arise from BACE1 deficiency during development. To address
      this question, we report that tamoxifen-inducible conditional BACE1 knockout mice
      in which the Bace1 gene was ablated in the adult largely lacked the phenotypes
      observed in germline BACE1 knockout mice. However, one BACE1-null phenotype was
      induced after Bace1 gene deletion in the adult mouse brain. This phenotype showed
      reduced length and disorganization of the hippocampal mossy fiber infrapyramidal
      bundle, the axonal pathway of dentate gyrus granule cells that is maintained by
      neurogenesis in the mouse brain. This defect in axonal organization correlated
      with reduced BACE1-mediated cleavage of the neural cell adhesion protein close
      homolog of L1 (CHL1), which has previously been associated with axon guidance.
      Although our results indicate that BACE1 inhibition in the adult mouse brain may
      avoid phenotypes associated with BACE1 deficiency during embryonic and postnatal
      development, they also suggest that BACE1 inhibitor drugs developed for treating
      AD may disrupt the organization of an axonal pathway in the hippocampus, an
      important structure for learning and memory.

PMID- 30232229
TI  - The hallmarks of successful anticancer immunotherapy.
AB  - Immunotherapy is revolutionizing the clinical management of multiple tumors.
      However, only a fraction of patients with cancer responds to immunotherapy, and
      currently available immunotherapeutic agents are expensive and generally
      associated with considerable toxicity, calling for the identification of robust
      predictive biomarkers. The overall genomic configuration of malignant cells,
      potentially favoring the emergence of immunogenic tumor neoantigens, as well as
      specific mutations that compromise the ability of the immune system to recognize
      or eradicate the disease have been associated with differential sensitivity to
      immunotherapy in preclinical and clinical settings. Along similar lines, the
      type, density, localization, and functional orientation of the immune infiltrate
      have a prominent impact on anticancer immunity, as do features of the tumor
      microenvironment linked to the vasculature and stroma, and systemic factors
      including the composition of the gut microbiota. On the basis of these
      considerations, we outline the hallmarks of successful anticancer immunotherapy.

PMID- 30232228
TI  - Repurposing ciclopirox as a pharmacological chaperone in a model of congenital
      erythropoietic porphyria.
AB  - Congenital erythropoietic porphyria is a rare autosomal recessive disease
      produced by deficient activity of uroporphyrinogen III synthase, the fourth
      enzyme in the heme biosynthetic pathway. The disease affects many organs, can be
      life-threatening, and currently lacks curative treatments. Inherited mutations
      most commonly reduce the enzyme's stability, altering its homeostasis and
      ultimately blunting intracellular heme production. This results in uroporphyrin
      by-product accumulation in the body, aggravating associated pathological symptoms
      such as skin photosensitivity and disfiguring phototoxic cutaneous lesions. We
      demonstrated that the synthetic marketed antifungal ciclopirox binds to the
      enzyme, stabilizing it. Ciclopirox targeted the enzyme at an allosteric site
      distant from the active center and did not affect the enzyme's catalytic role.
      The drug restored enzymatic activity in vitro and ex vivo and was able to
      alleviate most clinical symptoms of congenital erythropoietic porphyria in a
      genetic mouse model of the disease at subtoxic concentrations. Our findings
      establish a possible line of therapeutic intervention against congenital
      erythropoietic porphyria, which is potentially applicable to most of deleterious
      missense mutations causing this devastating disease.

PMID- 30232230
TI  - The PTH/PTHrP-SIK3 pathway affects skeletogenesis through altered mTOR signaling.
AB  - Studies have suggested a role for the mammalian (or mechanistic) target of
      rapamycin (mTOR) in skeletal development and homeostasis, yet there is no
      evidence connecting mTOR with the key signaling pathways that regulate
      skeletogenesis. We identified a parathyroid hormone (PTH)/PTH-related peptide
      (PTHrP)-salt-inducible kinase 3 (SIK3)-mTOR signaling cascade essential for
      skeletogenesis. While investigating a new skeletal dysplasia caused by a
      homozygous mutation in the catalytic domain of SIK3, we observed decreased
      activity of mTOR complex 1 (mTORC1) and mTORC2 due to accumulation of DEPTOR, a
      negative regulator of both mTOR complexes. This SIK3 syndrome shared skeletal
      features with Jansen metaphyseal chondrodysplasia (JMC), a disorder caused by
      constitutive activation of the PTH/PTHrP receptor. JMC-derived chondrocytes
      showed reduced SIK3 activity, elevated DEPTOR, and decreased mTORC1 and mTORC2
      activity, indicating a common mechanism of disease. The data demonstrate that
      SIK3 is an essential positive regulator of mTOR signaling that functions by
      triggering DEPTOR degradation in response to PTH/PTHrP signaling during
      skeletogenesis.

PMID- 30232232
TI  - Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial
      cell activities in hippocampus of traumatic brain injury rats.
AB  - The abnormally high nucleotide-binding oligomerization domain (NOD)-like receptor
      family pyrin domain containing 3 (NLRP3) inflammasome activity is a typical
      characteristic of traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly
      selective alpha-2 adrenergic receptor agonist that inhibits the activation of
      NLRP3. Thus, it was hypothesized that Dex could attenuate TBI by inhibiting NLRP3
      inflammasome activity in hippocampus. Rats were subjected to controlled cortical
      impact method to induce TBI, and treated with Dex. The effect of Dex treatment on
      the cognitive function, NLRP3 activity, and microglial activation in rat brain
      tissues was assessed. The administration of Dex improved performance of TBI rats
      in Morris water maze (MWM) test, which was associated with the increased neurone
      viability and suppressed microglia activity. Moreover, the administration of Dex
      inhibited the neuroinflammation in brain tissue as well as the expressions of
      NLRP3 and caspase-1. Additionally, Dex and NLRP3 inhibitor, BAY-11-7082 had a
      synergistic effect in inhibiting NLRP3/caspase-1 axis activity and improving TBI.
      The findings outlined in the current study indicated that the improvement effect
      of Dex on TBI was related to its effect on NLRP3 activity.

PMID- 30232231
TI  - Network pharmacology-based identification of major component of Angelica sinensis
      and its action mechanism for the treatment of acute myocardial infarction.
AB  - Background: To decipher the mechanisms of Angelica sinensis for the treatment of
      acute myocardial infarction (AMI) using network pharmacology analysis. Methods:
      Databases were searched for the information on constituents, targets, and
      diseases. Cytoscape software was used to construct the constituent-target-disease
      network and screen the major targets, which were annotated with the DAVID
      (Database for Annotation, Visualization and Integrated Discovery) tool. The
      cardioprotective effects of Angelica sinensis polysaccharide (ASP), a major
      component of A. sinensis, were validated both in H9c2 cells subjected to
      simulated ischemia by oxygen and glucose deprivation and in rats with AMI by
      ligation of the left anterior coronary artery. Results: We identified 228 major
      targets against AMI injury for A. sinensis, which regulated multiple pathways and
      hit multiple targets involved in several biological processes. ASP significantly
      decreased endoplasmic reticulum (ER) stress-induced cell death both in vitro and
      in vivo In ischemia injury rats, ASP treatment reduced infarct size and preserved
      heart function. ASP enhanced activating transcription factor 6 (ATF6) activity,
      which improved ER-protein folding capacity. ASP activated the expression of p-AMP
      activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor
      gamma coactivator 1alpha (PGC1alpha). Additionally, ASP attenuated levels of
      proinflammatory cytokines and maintained a balance in the oxidant/antioxidant
      levels after AMI. Conclusion: In silico analysis revealed the associations
      between A. sinensis and AMI through multiple targets and several key signaling
      pathways. Experimental data indicate that ASP protects the heart against ischemic
      injury by activating ATF6 to ameliorate the detrimental ER stress. ASP's effects
      could be mediated via the activation of AMPK-PGC1alpha pathway.

PMID- 30232233
TI  - Relationship between platelet parameters and sudden sensorineural hearing loss: a
      systematic review and meta-analysis.
AB  - Recent years, the discussion about whether platelets participant in the
      development of sudden sensorineural hearing loss (SSHL) continues and many
      studies on the relationship between them have come to our attention. Some studies
      believe that platelet parameters have significantly changed in patients with
      SSHL, while some not, controversially. Therefore, to investigate the association
      between platelet parameters, including mean platelet volume (MPV), platelet
      distribution width (PDW) and platelet count (PLT), and SSHL, expecting to resolve
      controversy and provide clinical evidence for diagnosis and monitoring of SSHL.
      Basic methods: Literature was retrieved searching electronic databases (PubMed,
      Embase, Cochrane, and Scopus) and searching references of related articles by
      hand. A total of 18 case-control studies involving 1837/1734 subjects
      (SSHL/control) were included. Meta-analysis showed there was no difference
      between the patients who suffered SSHL and healthy controls in MPV level
      [standard mean difference (SMD) (95% confidence interval (CI)) = 0.16 (-0.07,
      0.40), I 2 = 80%, P<0.00001] and PLT [SMD (95% CI) = -0.03(-0.18, 0.12), I 2 =
      73%, P<0.00001]. While PDW exhibited significant difference [SMD (95% CI) = 0.85
      (0.20, 1.49), I 2 = 93%, P<0.00001]. Subgroup analysis about geographical area
      suggested PLT have obvious evidence for SSHL in Eastern country [SMD (95% CI) =
      0.23 (0.14, 0.33), I 2 = 0%, P=0.81]. Our study did not support a correlation
      between MPV and SSHL, while PLT may have clinical significance for SSHL in
      Eastern country. With insufficient data to explore the resource of heterogeneity
      for PDW, there is no decisive conclusion reached.

PMID- 30232234
TI  - An accurate and cost-effective alternative method for measuring cell migration
      with the circular wound closure assay.
AB  - Cell migration is important in many physiological and pathological processes.
      Mechanisms of two-dimensional cell migration have been investigated most commonly
      by evaluating rates of cell migration into linearly scratched zones on the
      surfaces of culture plates. Here, we present a detailed description of a simple
      adaptation for the well-known and popular wound closure assay, using a circular
      wound instead of a straight line. This method demonstrates improved precision,
      reproducibility, and sampling objectivity for measurements of wound sizes as
      compared with classic scratch assays, enabling more accurate calculations of
      migration rate. The added benefits of the method are simplicity and low cost as
      compared with commercially available assays for generating circular wounds.

PMID- 30232235
TI  - The potential role of MGMT rs12917 polymorphism in cancer risk: an updated
      pooling analysis with 21010 cases and 34018 controls.
AB  - In the present study, we aimed at determining the potential role of rs12917
      polymorphism of the O-6-methylguanine-DNA methyltransferase (MGMT) gene in the
      occurrence of cancer. Based on the available data from the online database, we
      performed an updated meta-analysis. We retrieved 537 articles from our database
      research and finally selected a total of 54 case-control studies (21010 cases and
      34018 controls) for a series of pooling analyses. We observed an enhanced risk in
      cancer cases compared with controls, using the genetic models T/T compared with
      C/C (P-value of association test <0.001; odds ratio (OR) = 1.29) and T/T compared
      with C/C+C/T (P<0.001; OR = 1.32). We detected similar positive results in the
      subgroups 'Caucasian', and 'glioma' (all P<0.05; OR > 1). However, we detected
      negative results in our analyses of most of the other subgroups (P>0.05). Begg's
      and Egger's tests indicated that the results were free of potential publication
      bias, and sensitivity analysis suggested the stability of the pooling results. In
      summary, the T/T genotype of MGMT rs12917 is likely to be linked to an enhanced
      susceptibility to cancer overall, especially glioma, in the Caucasian population.

PMID- 30232237
TI  - Angiopoetin-like 4 in sickle cell retinopathy.
AB  - This correspondence provides a comment on the recent review article by Yang et
      al. [Biosci. Rep. (2018) 38, BSR20180557, https://doi.org/10.1042/BSR20180557].

PMID- 30232236
TI  - Tanshinone IIA promotes the apoptosis of fibroblast-like synoviocytes in
      rheumatoid arthritis by up-regulating lncRNA GAS5.
AB  - Rheumatoid arthritis (RA) is a common chronic autoimmune joint disease
      characteristic of elevated proliferation and infiltration of fibroblast-like
      synoviocytes (FLS). Here, we aimed to explore the mechanisms of the Tanshinone
      IIA (Tan IIA)-induced apoptosis of FLS from patients with RA (termed RAFLS). Cell
      Counting Kit-8 (CCK-8) assay and Annexin V staining revealed that RAFLS viability
      decreased and apoptosis increased after Tan IIA treatment. Long non-coding RNA
      (lncRNA) GAS5 expression was significantly decreased in the synovial tissues and
      RAFLS, while Tan IIA treatment resulted in an up-regulation of GAS5.
      Consistently, knockdown of GAS5 using siRNA inhibited RAFLS apoptosis.
      Mechanistically, GAS5 knockdown down-regulated the expression of cleaved caspase
      3 and caspase-9 in the RAFLS cells and activated the phosphoinositide 3-kinase
      (PI3K)/AKT signaling pathway. These data indicate that Tan IIA promotes RAFLS
      apoptosis by up-regulating lncRNA GAS5, with enhanced expression of cleaved
      caspase-3/caspase-9 and inhibited PI3K/AKT signaling.

PMID- 30232238
TI  - Sodium-glucose transporter 2 inhibition and cardiovascular events in patients
      with diabetes: information from clinical trials and observational real-world
      data.
AB  - Cardiovascular (CV) disease (CVD) is the main cause of morbidity and mortality in
      patients with type 2 diabetes mellitus (T2DM). Despite optimal glycaemic control,
      standard antihyperglycaemic therapy failed to impact CV events in intervention
      trials; therefore, the U.S. Food and Drug Administration (FDA) and the European
      Medicines Agency (EMA) issued a guidance to the pharmaceutical industry to
      specifically assess the CV outcomes and safety of new glucose-lowering drugs.
      Amongst them, sodium-glucose transporter 2 (SGLT2) inhibitors proved to not only
      provide good tolerance, few adverse effects, and good glycometabolic control, but
      also striking reduction in the risk of CV events. In this review, data from the
      main randomised controlled trials are presented, including post-hoc analyses
      looking into several aspects of CV protection. Moreover, the main findings from
      observational real-world studies to date are described, overall reassuring as
      regards to CV safety and efficacy of SGLT2 inhibitors. Finally, several
      mechanisms which might contribute to the cardioprotective effect of SGLT2
      inhibition are depicted, including findings from recent mechanistic studies.

PMID- 30232239
TI  - The intestinal microbiota in the pathogenesis of inflammatory bowel diseases: new
      insights into complex disease.
AB  - Inflammatory bowel diseases (IBD) are a group of chronic diseases of increasing
      worldwide prevalence characterized by gastrointestinal (GI) inflammation leading
      to debilitating symptoms and complications. The contribution of the intestinal
      microbiota to the pathogenesis and etiology of these diseases is an area of
      active research interest. Here, we discuss key mechanisms underlying the chronic
      inflammation seen in IBD as well as evidence implicating the intestinal
      microbiota in the development and potentiation of that inflammation. We also
      discuss recently published work in areas of interest within the field of
      microbial involvement in IBD pathogenesis - the importance of proper microecology
      within the GI tract, the evidence that the intestinal microbiota transduces
      environmental and genetic risk factors for IBD, and the mechanisms by which
      microbial products contribute to communication between microbe and host. There is
      an extensive body of published research on the evidence for microbial involvement
      in IBD; the goal of this review is to highlight the growing edges of the field
      where exciting and innovative research is pushing the boundaries of the
      conceptual framework of the role of the intestinal microbiota in IBD
      pathogenesis.

PMID- 30232240
TI  - Imaging and analysis of a three-dimensional spider web architecture.
AB  - Spiders are abundantly found in nature and most ecosystems, making up more than
      47 000 species. This ecological success is in part due to the exceptional
      mechanics of the spider web, with its strength, toughness, elasticity and
      robustness, which originate from its hierarchical structures all the way from
      sequence design to web architecture. It is a unique example in nature of high
      performance material design. In particular, to survive in different environments,
      spiders have optimized and adapted their web architecture by providing housing,
      protection, and an efficient tool for catching prey. The most studied web in
      literature is the two-dimensional (2D) orb web, which is composed of radial and
      spiral threads. However, only 10% of spider species are orb-web weavers, and
      three-dimensional (3D) webs, such as funnel, sheet or cobwebs, are much more
      abundant in nature. The complex spatial network and microscale size of silk
      fibres are significant challenges towards determining the topology of 3D webs,
      and only a limited number of previous studies have attempted to quantify their
      structure and properties. Here, we focus on developing an innovative experimental
      method to directly capture the complete digital 3D spider web architecture with
      micron scale resolution. We built an automatic segmentation and scanning platform
      to obtain high-resolution 2D images of individual cross-sections of the web that
      were illuminated by a sheet laser. We then developed image processing algorithms
      to reconstruct the digital 3D fibrous network by analysing the 2D images. This
      digital network provides a model that contains all of the structural and
      topological features of the porous regions of a 3D web with high fidelity, and
      when combined with a mechanical model of silk materials, will allow us to
      directly simulate and predict the mechanical response of a realistic 3D web under
      mechanical loads. Our work provides a practical tool to capture the architecture
      of sophisticated 3D webs, and could lead to studies of the relation between
      architecture, material and biological functions for numerous 3D spider web
      applications.

PMID- 30232241
TI  - Orderliness predicts academic performance: behavioural analysis on campus
      lifestyle.
AB  - Quantitative understanding of relationships between students' behavioural
      patterns and academic performances is a significant step towards personalized
      education. In contrast to previous studies that were mainly based on
      questionnaire surveys, recent literature suggests that unobtrusive digital data
      bring us unprecedented opportunities to study students' lifestyles in the campus.
      In this paper, we collect behavioural records from undergraduate students' (N =
      18 960) smart cards and propose two high-level behavioural characters,
      orderliness and diligence. The former is a novel entropy-based metric that
      measures the regularity of campus daily life, which is estimated here based on
      temporal records of taking showers and having meals. Empirical analyses on such
      large-scale unobtrusive behavioural data demonstrate that academic performance
      (GPA) is significantly correlated with orderliness. Furthermore, we show that
      orderliness is an important feature to predict academic performance, which
      improves the prediction accuracy even in the presence of students' diligence.
      Based on these analyses, education administrators could quantitatively understand
      the major factors leading to excellent or poor performance, detect undesirable
      abnormal behaviours in time and thus implement effective interventions to better
      guide students' campus lives at an early stage when necessary.

PMID- 30232242
TI  - Multi-lag tone-entropy in neonatal stress.
AB  - Heart rate variability (HRV) has been analysed using linear and nonlinear
      methods. In the framework of a controlled neonatal stress model, we applied tone
      entropy (T-E) analysis at multiple lags to understand the influence of external
      stressors on healthy term neonates. Forty term neonates were included in the
      study. HRV was analysed using multi-lag T-E at two resting and two stress phases
      (heel stimulation and a heel stick blood drawing phase). Higher mean entropy
      values and lower mean tone values when stressed showed a reduction in randomness
      with increased sympathetic and reduced parasympathetic activity. A ROC analysis
      was used to estimate the diagnostic performances of tone and entropy and
      combining both features. Comparing the resting and simulation phase separately,
      the performance of tone outperformed entropy, but combining the two in a
      quadratic linear regression model, neonates in resting as compared to stress
      phases could be distinguished with high accuracy. This raises the possibility
      that when applied across short time segments, multi-lag T-E becomes an additional
      tool for more objective assessment of neonatal stress.

PMID- 30232243
TI  - Intercellular adhesion promotes clonal mixing in growing bacterial populations.
AB  - Dense bacterial communities, known as biofilms, can have functional spatial
      organization driven by self-organizing chemical and physical interactions between
      cells, and their environment. In this work, we investigated intercellular
      adhesion, a pervasive property of bacteria in biofilms, to identify effects on
      the internal structure of bacterial colonies. We expressed the self-recognizing
      ag43 adhesin protein in Escherichia coli to generate adhesion between cells,
      which caused aggregation in liquid culture and altered microcolony morphology on
      solid media. We combined the adhesive phenotype with an artificial colony
      patterning system based on plasmid segregation, which marked clonal lineage
      domains in colonies grown from single cells. Engineered E. coli were grown to
      colonies containing domains with varying adhesive properties, and investigated
      with microscopy, image processing and computational modelling techniques. We
      found that intercellular adhesion elongated the fractal-like boundary between
      cell lineages only when both domains within the colony were adhesive, by
      increasing the rotational motion during colony growth. Our work demonstrates that
      adhesive intercellular interactions can have significant effects on the spatial
      organization of bacterial populations, which can be exploited for biofilm
      engineering. Furthermore, our approach provides a robust platform to study the
      influence of intercellular interactions on spatial structure in bacterial
      populations.

PMID- 30232244
TI  - The atypically high modulus of pollen exine.
AB  - Sporopollenin, the polymer comprising the exine (outer solid shell) of pollen, is
      recognized as one of the most chemically and mechanically stable naturally
      occurring organic substances. The elastic modulus of sporopollenin is of great
      importance to understanding the adhesion, transport and protective functions of
      pollen grains. In addition, this fundamental mechanical property is of
      significant interest in using pollen exine as a material for drug delivery,
      reinforcing fillers, sensors and adhesives. Yet, the literature reports of the
      elastic modulus of sporopollenin are very limited. We provide the first report of
      the elastic modulus of sporopollenin from direct indentation of pollen particles
      of three plant species: ragweed (Ambrosia artemisiifolia), pecan (Carya
      illinoinensis) and Kentucky bluegrass (Poa pratensis). The modulus was determined
      with atomic force microscopy by using direct nanomechanical mapping of the pollen
      shell surface. The moduli were atypically high for non-crystalline organic
      biomaterials, with average values of 16 +/- 2.5 GPa (ragweed), 9.5 +/- 2.3 GPa
      (pecan) and 16 +/- 4.0 GPa (Kentucky bluegrass). The amorphous pollen exine has a
      modulus exceeding known non-crystalline biomaterials, such as lignin (6.7 GPa)
      and actin (1.8 GPa). In addition to native pollen, we have investigated the
      effects of exposure to a common preparative base-acid chemical treatment and
      elevated humidity on the modulus. Base-acid treatment reduced the ragweed modulus
      by up to 58% and water vapour exposure at 90% relative humidity reduced the
      modulus by 54% (pecan) and 72% (Kentucky bluegrass). These results are in
      agreement with recently published estimates of the modulus of base-acid-treated
      ragweed pollen of 8 GPa from fitting to mechanical properties of ragweed pollen
      epoxy composites.

PMID- 30232245
TI  - Understanding the influence of silicone elastomer properties on wedge-shaped
      microstructured dry adhesives loaded in shear.
AB  - Anisotropic, gecko-inspired, microstructured adhesives are one of the most
      promising solutions for many applications in robotics and biomedical applications
      that require controllable adhesives to grip flat surfaces. In such adhesives,
      normal adhesion is negligible when loaded solely in the normal direction, but
      becomes available when the adhesive is loaded in shear first. However, much
      remains to be learned regarding the friction and failure mechanisms of
      microstructures loaded in shear. In response, we analysed the load-displacement
      profiles of wedge-shaped microstructured adhesives comprised of nine different
      silicone elastomers and their mixtures loaded in shear. The results show that the
      friction profile depends on at least three factors related to material
      properties: interfacial adhesion strength in the normal direction (work of
      separation), elastic modulus and the sample's imperfections (e.g. contamination,
      misalignment and moulding errors). Moreover, the work of separation influences
      the maximum friction load such that for materials with the same elastic modulus,
      the strongest interfacial adhesion yields the lowest friction force. To explain
      this, we suggest that strongly adhering materials will lead to a macroscopic
      frictional sliding of the array rather than previously reported stick-slip
      behaviour.

PMID- 30232247
TI  - Prestroke physical activity to reduce stroke severity: Moving to lower risk with
      light activity.

PMID- 30232246
TI  - Smartphone motor testing to distinguish idiopathic REM sleep behavior disorder,
      controls, and PD.
AB  - OBJECTIVE: We sought to identify motor features that would allow the delineation
      of individuals with sleep study-confirmed idiopathic REM sleep behavior disorder
      (iRBD) from controls and Parkinson disease (PD) using a customized smartphone
      application. METHODS: A total of 334 PD, 104 iRBD, and 84 control participants
      performed 7 tasks to evaluate voice, balance, gait, finger tapping, reaction
      time, rest tremor, and postural tremor. Smartphone recordings were collected both
      in clinic and at home under noncontrolled conditions over several days. All
      participants underwent detailed parallel in-clinic assessments. Using only the
      smartphone sensor recordings, we sought to (1) discriminate whether the
      participant had iRBD or PD and (2) identify which of the above 7 motor tasks were
      most salient in distinguishing groups. RESULTS: Statistically significant
      differences based on these 7 tasks were observed between the 3 groups. For the 3
      pairwise discriminatory comparisons, (1) controls vs iRBD, (2) controls vs PD,
      and (3) iRBD vs PD, the mean sensitivity and specificity values ranged from 84.6%
      to 91.9%. Postural tremor, rest tremor, and voice were the most discriminatory
      tasks overall, whereas the reaction time was least discriminatory. CONCLUSIONS:
      Prodromal forms of PD include the sleep disorder iRBD, where subtle motor
      impairment can be detected using clinician-based rating scales (e.g., Unified
      Parkinson's Disease Rating Scale), which may lack the sensitivity to detect and
      track granular change. Consumer grade smartphones can be used to accurately
      separate not only iRBD from controls but also iRBD from PD participants,
      providing a growing consensus for the utility of digital biomarkers in early and
      prodromal PD.

PMID- 30232249
TI  - Vascular risk burden, brain health, and next steps.

PMID- 30232248
TI  - Vascular risk at younger ages most strongly associates with current and future
      brain volume.
AB  - OBJECTIVE: Given the potential therapeutic effect of vascular disease control
      timing to reduce dementia risk, we investigated the age-related influences of
      vascular risk factor burden on brain structure throughout the lifespan. METHODS:
      We studied participants from the community-based prospective Framingham Heart
      Study. Overall vascular risk factor burden was calculated according to the
      Framingham Stroke Risk Profile, a validated algorithm that predicts stroke risk.
      Brain volume was estimated by MRI. We used cross-sectional data to examine how
      the strength of association between vascular risk factor burden and brain volume
      changed across each age decade from age 45-54 years through to 85-94 years (N =
      2,887). Second, we leveraged up to 40 years of longitudinal data to determine how
      the strength of association between vascular risk factor burden and brain volume
      changed when vascular risk factors were examined at progressively earlier ages (N
      = 7,868). RESULTS: In both cross-sectional and longitudinal analyses, higher
      vascular risk factor burden was associated with lower brain volume across each
      age decade. In the cross-sectional analysis, the strength of this association
      decreased with each decade of advancing age (p for trend < 0.0001). In
      longitudinal analysis, the strength of association between vascular risk factor
      burden and brain volume was stronger when vascular risk factors were measured at
      younger ages. For example, vascular risk factor burden was most strongly
      associated with lower brain volume in later life when vascular risk factors were
      measured at age 45 years. CONCLUSION: Vascular risk factors at younger ages
      appear to have detrimental effects on current and future brain volume.

PMID- 30232250
TI  - Primary angiitis of the CNS and reversible cerebral vasoconstriction syndrome: A
      comparative study.
AB  - OBJECTIVES: To further improve the distinction between primary angiitis of the
      CNS (PACNS) and reversible cerebral vasoconstriction syndrome (RCVS). METHODS: We
      compared 2 large French cohorts of patients with PACNS (n = 110, retrospectively
      and prospectively enrolled) and RCVS (n = 173, prospectively enrolled). RESULTS:
      Patients with RCVS were predominantly female (p < 0.0001), with migraines (p <
      0.0001), and were more often exposed to vasoactive substances (p < 0.0001) or
      postpartum (p = 0.002) than patients with PACNS. Headache, especially thunderclap
      headache, was more frequent in RCVS (both p < 0.0001). Thunderclap headache was
      absent in only 6% of patients with RCVS and was mainly recurrent (87%) and
      provoked (77%) mostly by sexual intercourse, exertion, or emotion. All other
      neurologic symptoms (motor deficit, seizure, cognitive disorder, or vigilance
      impairment, all p < 0.0001) were more frequent in PACNS. At admission, brain CT
      or MRI was abnormal in all patients with PACNS and in 31% of patients with RCVS
      (p < 0.0001). Acute ischemic stroke was more frequent in PACNS than in RCVS (p <
      0.0001). Although intracerebral hemorrhage was more frequent in PACNS (p =
      0.006), subarachnoid hemorrhage and vasogenic edema predominated in RCVS (p =
      0.04 and p = 0.01, respectively). Multiple small deep infarcts, extensive deep
      white matter lesions, tumor-like lesions, or multiple gadolinium-enhanced lesions
      were observed only in PACNS, whereas cervical artery dissection was found only in
      RCVS. CONCLUSIONS: Our study confirms that careful analysis of clinical context,
      headache features, and patterns of brain lesions can distinguish PACNS and RCVS
      within the first few days of admission in most cases. However, diagnosis remains
      challenging in a few cases.

PMID- 30232251
TI  - Prestroke physical activity could influence acute stroke severity (part of
      PAPSIGOT).
AB  - OBJECTIVE: To investigate the influence of prestroke physical activity (PA) on
      acute stroke severity. METHODS: Data from patients with first stroke were
      retrieved from registries with a cross-sectional design. The variables were PA,
      age, sex, smoking, diabetes, hypertension and statin treatment, stroke severity,
      myocardial infarction, new stroke during hospital stay, and duration of inpatient
      care at stroke unit. PA was assessed with Saltin-Grimby's 4-level Physical
      Activity Level Scale, and stroke severity was assessed with the National
      Institutes of Health Stroke Scale (NIHSS). Logistic regression was used to
      predict stroke severity, and negative binomial regression was used to compare the
      level of PA and stroke severity. RESULTS: The study included 925 patients with a
      mean age of 73.1 years, and 45.2% were women. Patients who reported light or
      moderate PA levels were more likely to present a mild stroke (NIHSS score 0 to 5)
      compared with physically inactive patients in a model that also included younger
      age as a predictor (odds ratio = 2.02 for PA and odds ratio = 0.97 for age). The
      explanatory value was limited at 6.8%. Prestroke PA was associated with less
      severe stroke, and both light PA such as walking at least 4 h/wk and moderate PA
      2-3 h/wk appear to be beneficial. Physical inactivity was associated with
      increased stroke severity. CONCLUSIONS: This study suggests that PA and younger
      age could result in a less severe stroke. Both light PA such as walking at least
      4 h/wk and moderate PA 2-3 h/wk appear to be beneficial.

PMID- 30232252
TI  - Changes in subjective experience elicited by direct stimulation of the human
      orbitofrontal cortex.
AB  - OBJECTIVE: We applied direct cortical stimulation (DCS) to the orbitofrontal
      cortex (OFC) in neurosurgical patients implanted with intracranial electrodes to
      probe, with high anatomic precision, the causal link between the OFC and human
      subjective experience. METHODS: We administered 272 instances of DCS at 172 OFC
      sites in 22 patients with intractable focal epilepsy (from 2011 to 2017), none of
      whom had seizures originating from the OFC. RESULTS: Our observations revealed a
      rich variety of affective, olfactory, gustatory, and somatosensory changes in the
      subjective domain. Elicited experiences were largely neutral or negatively
      valenced (e.g., aversive smells and tastes, sadness, and anger). Evidence was
      found for preferential left lateralization of negatively valenced experiences and
      strong right lateralization of neutral effects. Moreover, most of the elicited
      effects were observed after stimulation of OFC tissue around the transverse
      orbital sulcus, and none were seen in the most anterior aspects of the OFC.
      CONCLUSIONS: Our study yielded 3 central findings: first, a dissociation between
      the "silent" anterior and nonsilent middle/posterior OFC where stimulation
      clearly elicits changes in subjective experience; second, evidence that the OFC
      might play a causal role in integrating affect and multimodal sensory
      experiences; and third, clear evidence for left lateralization of negatively
      valenced effects. Our findings provide important information for clinicians
      treating OFC injury or planning OFC resection and scientists seeking to
      understand the brain basis for the integration of sensation, cognition, and
      affect.

PMID- 30232253
TI  - Supine plasma NE predicts the pressor response to droxidopa in neurogenic
      orthostatic hypotension.
AB  - OBJECTIVE: To test whether the plasma levels of norepinephrine (NE) in patients
      with neurogenic orthostatic hypotension (nOH) predict their pressor response to
      droxidopa. METHODS: This was an observational study, which included patients with
      nOH. All patients had standardized autonomic function testing including
      determination of venous plasma catecholamine levels drawn through an indwelling
      catheter while resting supine. This was followed by a droxidopa titration with
      100 mg increments in successive days until relief of symptoms, side effects, or
      the maximum dose of 600 mg was reached. No response was defined as an increase of
      <10 mm Hg in systolic blood pressure (BP) after 3-minute standing 1 hour after
      droxidopa administration. Nonlinear regression models were used to determine the
      relationship between BP response and plasma NE levels. RESULTS: We studied 20
      patients with nOH due to Parkinson disease, pure autonomic failure, multiple
      system atrophy, or autoimmune autonomic neuropathies. Their supine plasma NE
      levels ranged from 44 to 850 pg/mL. Lower supine plasma NE levels were associated
      with greater pressor effect 1 hour after dose (R2 = 0.49) and higher standing BP
      (R2 = 0.45). Patients with no pressor response to droxidopa had higher NE levels
      (382 +/- 100 vs 115 +/- 20 pg/mL, p = 0.0014). A supine NE level of <219.5 pg/mL
      had 83% sensitivity and 93% specificity to predict a pressor response (area under
      the curve = 0.95, p = 0.0023). CONCLUSIONS: In patients with nOH, lower supine
      resting plasma NE levels are associated with a greater pressor effect of
      droxidopa treatment. This finding should help identify patients with nOH most
      likely to respond to standard doses of droxidopa. CLASSIFICATION OF EVIDENCE:
      This study provides Class I evidence that lower supine plasma NE levels
      accurately identify patients with nOH more likely to have a greater pressor
      effect from droxidopa.

PMID- 30232254
TI  - The Charcot-Marie-Tooth Functional Outcome Measure (CMT-FOM).
AB  - OBJECTIVE: The purpose of this study was to examine the feasibility, reliability,
      and convergent validity of the Charcot-Marie-Tooth Functional Outcome Measure
      (CMT-FOM), a new performance-based measure assessing functional ability in adults
      with CMT disease. METHODS: Adults with CMT type 1A (CMT1A) were recruited at the
      Universities of Rochester and Iowa. Participants were assessed using the CMT-FOM,
      CMT Exam Score (CMTES), and a symptom report. Test-retest reliability was
      examined using intraclass correlation coefficients, internal consistency using
      Cronbach alpha, and convergent and known-groups validity using Spearman rank
      analysis and the Mann-Whitney test. RESULTS: Forty-three individuals (70% women;
      mean age 41, SD 14.9 years) participated. The CMT-FOM (mean 25.3 +/- 8.7, range
      12-44/52) was moderately correlated with the CMTES (rho = 0.62; p < 0.0001) and
      exhibited acceptable reliability (intraclass correlation coefficient = 0.92) and
      internal consistency (Cronbach alpha = 0.81). The CMT-FOM discriminated between
      participants with clinically mild vs moderate-severe CMT1A. Participants with the
      mildest CMT1A who demonstrated a floor effect on the CMTES showed functional
      limitations on the CMT-FOM. CONCLUSIONS: The CMT-FOM is well tolerated and showed
      no floor/ceiling effects in an adult CMT1A cohort matching those likely to enter
      upcoming clinical trials. It appears to be reliable, and our data support
      convergent and known-groups validity in adults with CMT1A. Longitudinal studies
      further examining the psychometric properties of the CMT-FOM and its
      responsiveness to change before its application in therapeutic trials are
      necessary.

PMID- 30232255
TI  - MRI load of cerebral microvascular lesions and neurodegeneration, cognitive
      decline, and dementia.
AB  - OBJECTIVE: To explore the differential associations of neurodegeneration and
      microvascular lesion load with cognitive decline and dementia in older people and
      the modifying effect of the APOE genotype on these associations. METHODS: A
      sample of 436 participants (age >= 60 years) was derived from the population
      based Swedish National study on Aging and Care in Kungsholmen, Stockholm, and
      clinically examined at baseline (2001-2003) and 3 occasions during the 9-year
      follow-up. At baseline, we assessed microvascular lesion load using a summary
      score for MRI markers of lacunes, white matter hyperintensities (WMHs), and
      perivascular spaces and neurodegeneration load for markers of enlarged
      ventricles, smaller hippocampus, and smaller gray matter. We assessed cognitive
      function using the Mini-Mental State Examination (MMSE) test and diagnosed
      dementia following the Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition criteria. We analyzed data using linear mixed-effects, mediation, and
      random-effects Cox models. RESULTS: During the follow-up, 46 participants were
      diagnosed with dementia. Per 1-point increase in microvascular lesion and
      neurodegeneration score (range 0-3) was associated with multiple adjusted beta
      coefficients of -0.35 (95% confidence interval, -0.51 to -0.20) and -0.44 (-0.56
      to -0.32), respectively, for the MMSE score and multiple adjusted hazard ratios
      of 1.68 (1.12-2.51) and 2.35 (1.58-3.52), respectively, for dementia; carrying
      APOE epsilon4 reinforced the associations with MMSE decline. WMH volume changes
      during the follow-up mediated 66.9% and 12.7% of the total association of MMSE
      decline with the baseline microvascular score and neurodegeneration score,
      respectively. CONCLUSIONS: Both cerebral microvascular lesion and
      neurodegeneration loads are strongly associated with cognitive decline and
      dementia. The cognitive decline due to microvascular lesions is exacerbated by
      APOE epsilon4 and is largely attributed to progression and development of
      microvascular lesions.

PMID- 30232256
TI  - Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK
      in mouse cancers.
AB  - Potent immunosuppressive mechanisms within the tumor microenvironment contribute
      to the resistance of aggressive human cancers to immune checkpoint blockade (ICB)
      therapy. One of the main mechanisms for myeloid-derived suppressor cells (MDSCs)
      to induce T cell tolerance is through secretion of reactive nitrogen species
      (RNS), which nitrates tyrosine residues in proteins involved in T cell function.
      However, so far very few nitrated proteins have been identified. Here, using a
      transgenic mouse model of prostate cancer and a syngeneic cell line model of lung
      cancer, we applied a nitroproteomic approach based on chemical derivation of 3
      nitrotyrosine and identified that lymphocyte-specific protein tyrosine kinase
      (LCK), an initiating tyrosine kinase in the T cell receptor signaling cascade, is
      nitrated at Tyr394 by MDSCs. LCK nitration inhibits T cell activation, leading to
      reduced interleukin 2 (IL2) production and proliferation. In human T cells with
      defective endogenous LCK, wild type, but not nitrated LCK, rescues IL2
      production. In the mouse model of castration-resistant prostate cancer (CRPC) by
      prostate-specific deletion of Pten, p53, and Smad4, CRPC is resistant to an ICB
      therapy composed of antiprogrammed cell death 1 (PD1) and anticytotoxic-T
      lymphocyte-associated protein 4 (CTLA4) antibodies. However, we showed that ICB
      elicits strong anti-CRPC efficacy when combined with an RNS neutralizing agent.
      Together, these data identify a previously unknown mechanism of T cell
      inactivation by MDSC-induced protein nitration and illuminate a clinical path
      hypothesis for combining ICB with RNS-reducing agents in the treatment of CRPC.

PMID- 30232257
TI  - Mechanics of mouse blastocyst hatching revealed by a hydrogel-based
      microdeformation assay.
AB  - Mammalian embryos are surrounded by an acellular shell, the zona pellucida.
      Hatching out of the zona is crucial for implantation and continued development of
      the embryo. Clinically, problems in hatching can contribute to failure in
      assisted reproductive intervention. Although hatching is fundamentally a
      mechanical process, due to limitations in methodology most studies focus on its
      biochemical properties. To understand the role of mechanical forces in hatching,
      we developed a hydrogel deformation-based method and analytical approach for
      measuring pressure in cyst-like tissues. Using this approach, we found that, in
      cultured blastocysts, pressure increased linearly, with intermittent falls.
      Inhibition of Na/K-ATPase led to a dosage-dependent reduction in blastocyst
      cavity pressure, consistent with its requirement for cavity formation. Reducing
      blastocyst pressure reduced the probability of hatching, highlighting the
      importance of mechanical forces in hatching. These measurements allowed us to
      infer details of microphysiology such as osmolarity, ion and water transport
      kinetics across the trophectoderm, and zona stiffness, allowing us to model the
      embryo as a thin-shell pressure vessel. We applied this technique to test whether
      cryopreservation, a process commonly used in assisted reproductive technology
      (ART), leads to alteration of the embryo and found that thawed embryos generated
      significantly lower pressure than fresh embryos, a previously unknown effect of
      cryopreservation. We show that reduced pressure is linked to delayed hatching.
      Our approach can be used to optimize in vitro fertilization (IVF) using precise
      measurement of embryo microphysiology. It is also applicable to other biological
      systems involving cavity formation, providing an approach for measuring forces in
      diverse contexts.

PMID- 30232258
TI  - Old puzzle of incommensurate crystal structure of calaverite AuTe2 and predicted
      stability of novel AuTe compound.
AB  - Gold is a very inert element, which forms relatively few compounds. Among them is
      a unique material-mineral calaverite, [Formula: see text] Besides being the only
      compound in nature from which one can extract gold on an industrial scale, it is
      a rare example of a natural mineral with incommensurate crystal structure.
      Moreover, it is one of few systems based on Au, which become superconducting (at
      elevated pressure or doped by Pd and Pt). Using ab initio calculations we
      theoretically explain these unusual phenomena in the picture of negative charge
      transfer energy and self-doping, with holes being largely in the Te [Formula: see
      text] bands. This scenario naturally explains incommensurate crystal structure of
      [Formula: see text], and it also suggests a possible mechanism of
      superconductivity. An ab initio evolutionary search for stable compounds in the
      Au-Te system confirms stability of [Formula: see text] and [Formula: see text]
      and leads to a prediction of an as yet unknown stable compound AuTe, which until
      now has not been synthesized.

PMID- 30232259
TI  - Phasic locus coeruleus activity regulates cortical encoding of salience
      information.
AB  - Phasic activation of locus coeruleus (LC)-norepinephrine (NE) neurons is
      associated with focused attention and behavioral responses to salient stimuli. We
      used cell-type-specific optogenetics and single-unit neurophysiology to identify
      how LC activity influences neural encoding of sensory information. We found that
      phasic, but not tonic, LC-NE photoactivation generated a distinct event-related
      potential (ERP) across cortical regions. Salient sensory stimuli (which innately
      trigger phasic LC activity) produced strong excitatory cortical responses during
      this ERP window. Application of weaker, nonsalient stimuli produced limited
      responses, but these responses were elevated to salient stimulus levels when they
      were temporally locked with phasic LC photoactivation. These results demonstrate
      that phasic LC activity enhances cortical encoding of salient stimuli by
      facilitating long-latency signals within target regions in response to stimulus
      intensity/salience. The LC-driven salience signal identified here provides a
      measure of phasic LC activity that can be used to investigate the LC's role in
      attentional processing across species.

PMID- 30232262
TI  - Collusion between neutralizing antibodies and other immune factions in the
      destruction of adenoviral vectors.

PMID- 30232260
TI  - Structural basis for cooperative regulation of KIX-mediated transcription
      pathways by the HTLV-1 HBZ activation domain.
AB  - The human T cell leukemia virus I basic leucine zipper protein (HTLV-1 HBZ)
      maintains chronic viral infection and promotes leukemogenesis through poorly
      understood mechanisms involving interactions with the KIX domain of the
      transcriptional coactivator CBP and its paralog p300. The KIX domain binds
      regulatory proteins at the distinct MLL and c-Myb/pKID sites to form binary or
      ternary complexes. The intrinsically disordered N-terminal activation domain of
      HBZ (HBZ AD) deregulates cellular signaling pathways by competing directly with
      cellular and viral transcription factors for binding to the MLL site and by
      allosterically perturbing binding of the transactivation domain of the
      hematopoietic transcription factor c-Myb. Crystal structures of the ternary KIX:c
      Myb:HBZ complex show that the HBZ AD recruits two KIX:c-Myb entities through
      tandem amphipathic motifs (L/V)(V/L)DGLL and folds into a long alpha-helix upon
      binding. Isothermal titration calorimetry reveals strong cooperativity in binding
      of the c-Myb activation domain to the KIX:HBZ complex and in binding of HBZ to
      the KIX:c-Myb complex. In addition, binding of KIX to the two HBZ (V/L)DGLL
      motifs is cooperative; the structures suggest that this cooperativity is achieved
      through propagation of the HBZ alpha-helix beyond the first binding motif. Our
      study suggests that the unique structural flexibility and the multiple
      interaction motifs of the intrinsically disordered HBZ AD are responsible for its
      potency in hijacking KIX-mediated transcription pathways. The KIX:c-Myb:HBZ
      complex provides an example of cooperative stabilization in a transcription
      factor:coactivator network and gives insights into potential mechanisms through
      which HBZ dysregulates hematopoietic transcriptional programs and promotes T cell
      proliferation.

PMID- 30232261
TI  - Substance P and IL-33 administered together stimulate a marked secretion of IL
      1beta from human mast cells, inhibited by methoxyluteolin.
AB  - Mast cells are critical for allergic and inflammatory responses in which the
      peptide substance P (SP) and the cytokine IL-33 are involved. SP (0.01-1 MUM)
      administered together with IL-33 (30 ng/mL) to human cultured LAD2 mast cells
      stimulates a marked increase (P < 0.0001) in secretion of the proinflammatory
      cytokine IL-1beta. Preincubation of LAD2 (30 min) with the SP receptor (NK-1)
      antagonists L-733,060 (10 MUM) or CP-96345 (10 uM) inhibits (P < 0.001) secretion
      of IL-1beta stimulated by either SP (1 MUM) or SP together with IL-33 (30 ng/mL).
      Surprisingly, secretion of IL-1beta stimulated by IL-33 is inhibited (P < 0.001)
      by each NK-1 antagonist. Preincubation with an antibody against the IL-33
      receptor ST2 inhibits (P < 0.0001) secretion of IL-1beta stimulated either by IL
      33 or together with SP. The combination of SP (1 MUM) with IL-33 (30 ng/mL)
      increases IL-1beta gene expression by 90-fold in LAD2 cells and by 200-fold in
      primary cultured mast cells from human umbilical cord blood. The combination of
      SP and IL-33 increases intracellular levels of IL-1beta in LAD2 by 100-fold and
      gene expression of IL-1beta and procaspase-1 by fivefold and pro-IL-1beta by
      twofold. Active caspase-1 is present even in unstimulated cells and is detected
      extracellularly. Preincubation of LAD2 cells with the natural flavonoid
      methoxyluteolin (1-100 mM) inhibits (P < 0.0001) secretion and gene expression of
      IL-1beta, procaspase-1, and pro-IL-1beta. Mast cell secretion of IL-1beta in
      response to SP and IL-33 reveals targets for the development of antiinflammatory
      therapies.

PMID- 30232263
TI  - Differential effects of partial and complete loss of TREM2 on microglial injury
      response and tauopathy.
AB  - Alzheimer's disease (AD), the most common form of dementia, is characterized by
      the abnormal accumulation of amyloid plaques and hyperphosphorylated tau
      aggregates, as well as microgliosis. Hemizygous missense variants in Triggering
      Receptor Expressed on Myeloid Cells 2 (TREM2) are associated with elevated risk
      for developing late-onset AD. These variants are hypothesized to result in loss
      of function, mimicking TREM2 haploinsufficiency. However, the consequences of
      TREM2 haploinsufficiency on tau pathology and microglial function remain unknown.
      We report the effects of partial and complete loss of TREM2 on microglial
      function and tau-associated deficits. In vivo imaging revealed that microglia
      from aged TREM2-haploinsufficient mice show a greater impairment in their injury
      response compared with microglia from aged TREM2-KO mice. In transgenic mice
      expressing mutant human tau, TREM2 haploinsufficiency, but not complete loss of
      TREM2, increased tau pathology. In addition, whereas complete TREM2 deficiency
      protected against tau-mediated microglial activation and atrophy, TREM2
      haploinsufficiency elevated expression of proinflammatory markers and exacerbated
      atrophy at a late stage of disease. The differential effects of partial and
      complete loss of TREM2 on microglial function and tau pathology provide important
      insights into the critical role of TREM2 in AD pathogenesis.

PMID- 30232264
TI  - Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome
      priming.
AB  - The NLRP3 inflammasome is an important regulator of inflammation and immunity. It
      is a multimolecular platform formed within cells that facilitates the activation
      of proinflammatory caspases to drive secretion of cytokines such as interleukin
      1beta (IL-1beta). Knowledge of the mechanisms regulating formation of the NLRP3
      inflammasome is incomplete. Here we report Cl- channel-dependent formation of
      dynamic ASC oligomers and inflammasome specks that remain inactive in the absence
      of K+ efflux. Formed after Cl- efflux exclusively, ASC specks are NLRP3
      dependent, reversible, and inactive, although they further prime inflammatory
      responses, accelerating and enhancing release of IL-1beta in response to a K+
      efflux-inducing stimulus. NEK7 is a specific K+ sensor and does not associate
      with NLRP3 under conditions stimulating exclusively Cl- efflux, but does after K+
      efflux, activating the complex driving inflammation. Our investigation delivers
      mechanistic understanding into inflammasome activation and the regulation of
      inflammatory responses.

PMID- 30232265
TI  - Phosphoethanolamine cellulose enhances curli-mediated adhesion of uropathogenic
      Escherichia coli to bladder epithelial cells.
AB  - Uropathogenic Escherichia coli (UPEC) are the major causative agents of urinary
      tract infections, employing numerous molecular strategies to contribute to
      adhesion, colonization, and persistence in the bladder niche. Identifying
      strategies to prevent adhesion and colonization is a promising approach to
      inhibit bacterial pathogenesis and to help preserve the efficacy of available
      antibiotics. This approach requires an improved understanding of the molecular
      determinants of adhesion to the bladder urothelium. We designed experiments using
      a custom-built live cell monolayer rheometer (LCMR) to quantitatively measure
      individual and combined contributions of bacterial cell surface structures [type
      1 pili, curli, and phosphoethanolamine (pEtN) cellulose] to bladder cell
      adhesion. Using the UPEC strain UTI89, isogenic mutants, and controlled
      conditions for the differential production of cell surface structures, we
      discovered that curli can promote stronger adhesive interactions with bladder
      cells than type 1 pili. Moreover, the coproduction of curli and pEtN cellulose
      enhanced adhesion. The LCMR enables the evaluation of adhesion under high-shear
      conditions to reveal this role for pEtN cellulose which escaped detection using
      conventional tissue culture adhesion assays. Together with complementary
      biochemical experiments, the results support a model wherein cellulose serves a
      mortar-like function to promote curli association with and around the bacterial
      cell surface, resulting in increased bacterial adhesion strength at the bladder
      cell surface.

PMID- 30232267
TI  - Alzheimer's disease: insights for risk evaluation and prevention in the Chinese
      population and the need for a comprehensive programme in Hong Kong/China.
AB  - With the ageing of the global population, China is projected to be impacted
      significantly by the rising number of patients with Alzheimer's disease (AD). A
      cure for AD is not yet available, so society should be prepared for an increasing
      AD-related burden. In this review, we examine this impending problem and provide
      overviews on (a) the magnitude of the problem of AD in Hong Kong/China in the
      near future; (b) the genetic and lifestyle risk factors that contribute to AD;
      (c) current diagnostic approaches and the potential of newly discovered genetic
      biomarkers for early detection; (d) medications, non-pharmacological
      interventions, and possible preventive measures; and (e) the need for social and
      psychological care from the community. In Hong Kong, primary care and AD-related
      support for at-risk individuals, patients, and caregivers are inadequate. A joint
      effort from the medical community, government, universities, non-governmental
      organisations/charities, and industry should initiate the development of a long
      term programme for AD. Finally, we outline recommendations for the relevant
      parties to consider.

PMID- 30232266
TI  - Repurposing type III polyketide synthase as a malonyl-CoA biosensor for metabolic
      engineering in bacteria.
AB  - Malonyl-CoA is an important central metabolite for the production of diverse
      valuable chemicals including natural products, but its intracellular availability
      is often limited due to the competition with essential cellular metabolism.
      Several malonyl-CoA biosensors have been developed for high-throughput screening
      of targets increasing the malonyl-CoA pool. However, they are limited for use
      only in Escherichia coli and Saccharomyces cerevisiae and require multiple signal
      transduction steps. Here we report development of a colorimetric malonyl-CoA
      biosensor applicable in three industrially important bacteria: E. coli,
      Pseudomonas putida, and Corynebacterium glutamicum RppA, a type III polyketide
      synthase producing red-colored flaviolin, was repurposed as a malonyl-CoA
      biosensor in E. coli Strains with enhanced malonyl-CoA accumulation were
      identifiable by the colorimetric screening of cells showing increased red color.
      Other type III polyketide synthases could also be repurposed as malonyl-CoA
      biosensors. For target screening, a 1,858 synthetic small regulatory RNA library
      was constructed and applied to find 14 knockdown gene targets that generally
      enhanced malonyl-CoA level in E. coli These knockdown targets were applied to
      produce two polyketide (6-methylsalicylic acid and aloesone) and two
      phenylpropanoid (resveratrol and naringenin) compounds. Knocking down these genes
      alone or in combination, and also in multiple different E. coli strains for two
      polyketide cases, allowed rapid development of engineered strains capable of
      enhanced production of 6-methylsalicylic acid, aloesone, resveratrol, and
      naringenin to 440.3, 30.9, 51.8, and 103.8 mg/L, respectively. The malonyl-CoA
      biosensor developed here is a simple tool generally applicable to metabolic
      engineering of microorganisms to achieve enhanced production of malonyl-CoA
      derived chemicals.

PMID- 30232268
TI  - Brugada syndrome trafficking-defective Nav1.5 channels can trap cardiac
      Kir2.1/2.2 channels.
AB  - Cardiac Nav1.5 and Kir2.1-2.3 channels generate Na (INa) and inward rectifier K
      (IK1) currents, respectively. The functional INa and IK1 interplay is reinforced
      by the positive and reciprocal modulation between Nav15 and Kir2.1/2.2 channels
      to strengthen the control of ventricular excitability. Loss-of-function mutations
      in the SCN5A gene, which encodes Nav1.5 channels, underlie several inherited
      arrhythmogenic syndromes, including Brugada syndrome (BrS). We investigated
      whether the presence of BrS-associated mutations alters IK1 density concomitantly
      with INa density. Results obtained using mouse models of SCN5A
      haploinsufficiency, and the overexpression of native and mutated Nav1.5 channels
      in expression systems - rat ventricular cardiomyocytes and human induced
      pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) - demonstrated that
      endoplasmic reticulum (ER) trafficking-defective Nav1.5 channels significantly
      decreased IK1, since they did not positively modulate Kir2.1/2.2 channels.
      Moreover, Golgi trafficking-defective Nav1.5 mutants produced a dominant negative
      effect on Kir2.1/2.2 and thus an additional IK1 reduction. Moreover, ER
      trafficking-defective Nav1.5 channels can be partially rescued by Kir2.1/2.2
      channels through an unconventional secretory route that involves Golgi reassembly
      stacking proteins (GRASPs). Therefore, cardiac excitability would be greatly
      affected in subjects harboring Nav1.5 mutations with Golgi trafficking defects,
      since these mutants can concomitantly trap Kir2.1/2.2 channels, thus unexpectedly
      decreasing IK1 in addition to INa.

PMID- 30232269
TI  - Leukotriene B4 promotes neovascularization and macrophage recruitment in murine
      wet-type AMD models.
AB  - Age-related macular degeneration (AMD), a progressive chronic disease of the
      central retina, is associated with aging and is a leading cause of blindness
      worldwide. Here, we demonstrate that leukotriene B4 (LTB4) receptor 1 (BLT1)
      promotes laser-induced choroidal neovascularization (CNV) in a mouse model for
      wet-type AMD. CNV was significantly less in BLT1-deficient (BLT1-KO) mice
      compared with BLT1-WT controls. Expression of several proangiogenic and
      profibrotic factors was lower in BLT1-KO eyes than in BLT1-WT eyes. LTB4
      production in the eyes was substantially increased in the early phase after laser
      injury. BLT1 was highly expressed in M2 macrophages in vitro and in vivo, and
      ocular BLT1+ M2 macrophages were increased in the aged eyes after laser injury.
      Furthermore, M2 macrophages were rapidly attracted by LTB4 and subsequently
      produced VEGF-A- through BLT1-mediated signaling. Consequently, intravitreal
      injection of M2 macrophages augmented CNV formation, which was attenuated by BLT1
      deficiency. Thus, laser-induced injury to the retina triggered LTB4 production
      and attracted M2 macrophages via BLT1, leading to development of CNV. A selective
      BLT1 antagonist (CP105696) and 3 LTB4 inhibitors (zileuton, MK-886, and bestatin)
      reduced CNV in a dose-dependent manner. CP105696 also inhibited the accumulation
      of BLT1+ M2 macrophages in the laser-injured eyes of aged mice. Together, these
      results indicate that the LTB4-BLT1 axis is a potentially novel therapeutic
      target for CNV of wet-type AMD.

PMID- 30232270
TI  - Laminin alpha1 is a genetic modifier of TGF-beta1-stimulated pulmonary fibrosis.
AB  - The pathogenetic mechanisms underlying the pathologic fibrosis in diseases such
      as idiopathic pulmonary fibrosis (IPF) are poorly understood. To identify genetic
      factors affecting susceptibility to IPF, we analyzed a murine genetic model of
      IPF in which a profibrotic cytokine (TGF-beta1) was expressed in the lungs of 10
      different inbred mouse strains. Surprisingly, the extent of TGF-beta1-induced
      lung fibrosis was highly strain dependent. Haplotype-based computational genetic
      analysis and gene expression profiling of lung tissue obtained from fibrosis
      susceptible and -resistant strains identified laminin alpha1 (Lama1) as a genetic
      modifier for susceptibility to IPF. Subsequent studies demonstrated that Lama1
      plays an important role in multiple processes that affect the pulmonary response
      to lung injury and susceptibility to fibrosis, which include: macrophage
      activation, fibroblast proliferation, myofibroblast transformation, and the
      production of extracellular matrix. Also, Lama1 mRNA expression was significantly
      increased in lung tissue obtained from IPF patients. These studies identify Lama1
      as the genetic modifier of TGF-beta1 effector responses that significantly
      affects the development of pulmonary fibrosis.

PMID- 30232271
TI  - Beclin-1 regulates cigarette smoke-induced kidney injury in a murine model of
      chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD), associated with cigarette smoke
      induced (CS-induced) emphysema, contributes significantly to the global health
      care burden of disease. Although chronic kidney disease (CKD) may occur in
      patients with COPD, the relationship between COPD and CKD remains unclear. Using
      a murine model of experimental COPD, we show that chronic CS exposure resulted in
      marked kidney injury and fibrosis, as evidenced by histological and
      ultrastructural changes, altered macrophage subpopulations, and expression of
      tissue injury, fibrosis, and oxidative stress markers. CS induced mitochondrial
      dysfunction, and increased autophagic flux in kidney tissues and in kidney
      tubular epithelial (HK-2) cells, as determined by LC3B turnover assays. Mice
      heterozygous for Beclin-1 (Becn1+/-) were protected from the development of
      kidney tissue injury and renal fibrosis in response to CS exposure, and displayed
      impaired basal and inducible mitochondrial turnover by mitophagy. Interestingly,
      CS caused a reduction of Beclin-1 expression in mouse kidneys and kidney tubular
      epithelial cells, attributed to increased autophagy-dependent turnover of Beclin
      1. These results suggest that Beclin-1 is required for CS-induced kidney injury
      and that reduced levels of Beclin-1 may confer renoprotection. These results
      identify the kidney as a target for CS-induced injury in COPD and the Beclin-1
      dependent autophagy pathway as a potential therapeutic target in CKD.

PMID- 30232272
TI  - IL-33 modulates inflammatory brain injury but exacerbates systemic
      immunosuppression following ischemic stroke.
AB  - Stroke triggers a complex inflammatory process in which the balance between pro-
      and antiinflammatory mediators is critical for the development of the brain
      infarct. However, systemic changes may also occur in parallel with brain
      inflammation. Here we demonstrate that administration of recombinant IL-33, a
      recently described member of the IL-1 superfamily of cytokines, promotes Th2-type
      effects following focal ischemic stroke, resulting in increased plasma levels of
      Th2-type cytokines and fewer proinflammatory (3-nitrotyrosine+F4/80+)
      microglia/macrophages in the brain. These effects of IL-33 were associated with
      reduced infarct size, fewer activated microglia and infiltrating cytotoxic
      (natural killer-like) T cells, and more IL-10-expressing regulatory T cells.
      Despite these neuroprotective effects, mice treated with IL-33 displayed
      exacerbated post-stroke lung bacterial infection in association with greater
      functional deficits and mortality at 24 hours. Supplementary antibiotics
      (gentamicin and ampicillin) mitigated these systemic effects of IL-33 after
      stroke. Our findings highlight the complex nature of the inflammatory mechanisms
      differentially activated in the brain and periphery during the acute phase after
      ischemic stroke. The data indicate that a Th2-promoting agent can provide
      neuroprotection without adverse systemic effects when given in combination with
      antibiotics.

PMID- 30232273
TI  - Human immunodeficiency virus infection induces lymphoid fibrosis in the BM-liver
      thymus-spleen humanized mouse model.
AB  - A major pathogenic feature associated with HIV infection is lymphoid fibrosis,
      which persists during antiretroviral therapy (ART). Lymphoid tissues play
      critical roles in the generation of antigen-specific immune response, and
      fibrosis disrupts the stromal network of lymphoid tissues, resulting in impaired
      immune cell trafficking and function, as well as immunodeficiency. Developing an
      animal model for investigating the impact of HIV infection-induced lymphoid
      tissue fibrosis on immunodeficiency and immune cell impairment is critical for
      therapeutics development and clinical translation. Said model will enable in vivo
      mechanistic studies, thus complementing the well-established surrogate model of
      SIV infection-induced lymphoid tissue fibrosis in macaques. We developed a
      potentially novel human immune system-humanized mouse model by coengrafting
      autologous fetal thymus, spleen, and liver organoids under the kidney capsule,
      along with i.v. injection of autologous fetal liver-derived hematopoietic stem
      cells, thus termed the BM-liver-thymus-spleen (BLTS) humanized mouse model. BLTS
      humanized mouse model supports development of human immune cells and human
      lymphoid organoids (human thymus and spleen organoids). HIV infection in BLTS
      humanized mice results in progressive fibrosis in human lymphoid tissues, which
      was associated with immunodeficiency in the lymphoid tissues, and lymphoid tissue
      fibrosis persists during ART, thus recapitulating clinical outcomes.

PMID- 30232275
TI  - The phosphatidic acid phosphatase lipin-1 facilitates inflammation-driven colon
      carcinogenesis.
AB  - Colon cancer is a devastating illness that is associated with gut inflammation.
      Here, we explored the possible role of lipin-1, a phosphatidic acid phosphatase,
      in the development of colitis-associated tumorigenesis. Azoxymethane and dextran
      sodium sulfate-treated (DSS-treated) animals deficient in lipin-1 harbored fewer
      tumors and carcinomas than WT animals due to decreased cellular proliferation,
      lower expression of antiapoptotic and protumorigenic factors, and a reduced
      infiltration of macrophages in colon tumors. They also displayed increased
      resistance to DSS-induced colitis by producing less proinflammatory cytokines and
      experiencing less immune infiltration. Lipin-1-deficient macrophages from the
      colon were less activated and displayed lower phosphatidic acid phosphatase
      activity than WT macrophages isolated from DSS-treated animals. Transference of
      WT macrophages into lipin-1-deficient animals was sufficient to increase colitis
      burden. Furthermore, treatment of lipin-1-deficient mice with IL-23 exacerbated
      colon inflammation. Analysis of human databases from colon cancer and ulcerative
      colitis patients showed that lipin-1 expression is increased in those disorders
      and correlates with the expression of the proinflammatory markers CXCL1 and
      CXCL2. And finally, clinically, LPIN1 expression had prognostic value in
      inflammatory and stem-cell subtypes of colon cancers. Collectively, these data
      demonstrate that lipin-1 is a critical regulator of intestinal inflammation and
      inflammation-driven colon cancer development.

PMID- 30232276
TI  - IFI16 filament formation in salivary epithelial cells shapes the anti-IFI16
      immune response in Sjogren's syndrome.
AB  - IFN-inducible protein 16 (IFI16) is an innate immune sensor that forms
      filamentous oligomers when activated by double-stranded DNA (dsDNA). Anti-IFI16
      autoantibodies occur in patients with Sjogren's syndrome (SS) and associate with
      severe phenotypic features. We undertook this study to determine whether the
      structural and functional properties of IFI16 play a role in its status as an SS
      autoantigen. IFI16 immunostaining in labial salivary glands (LSGs) yielded
      striking evidence of filamentous IFI16 structures in the cytoplasm of ductal
      epithelial cells, representing the first microscopic description of IFI16
      oligomerization in human tissues, to our knowledge. Transfection of cultured
      epithelial cells with dsDNA triggered the formation of cytoplasmic IFI16
      filaments with similar morphology to those observed in LSGs. We found that a
      majority of SS anti-IFI16 autoantibodies immunoprecipitate IFI16 more effectively
      in the oligomeric dsDNA-bound state. Epitopes in the C-terminus of IFI16 are
      accessible to antibodies in the DNA-bound oligomer and are preferentially
      targeted by SS sera. Furthermore, cytotoxic lymphocyte granule pathways (highly
      enriched in the SS gland) induce striking release of IFI16*dsDNA complexes from
      cultured cells. Our studies reveal that IFI16 is present in a filamentous state
      in the target tissue of SS and suggest that this property of DNA-induced filament
      formation contributes to its status as an autoantigen in SS. These studies
      highlight the role that tissue-specific modifications and immune effector
      pathways might play in the selection of autoantigens in rheumatic diseases.

PMID- 30232277
TI  - Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit
      against SIV.
AB  - Therapeutic strategies that augment antiviral immunity and reduce the viral
      reservoir are critical to achieving durable remission of HIV. The coinhibitory
      receptor programmed death-1 (PD-1) regulates CD8+ T cell dysfunction during
      chronic HIV and SIV infections. We previously demonstrated that in vivo blockade
      of PD-1 during chronic SIV infection improves the function of antiviral CD8+ T
      cells and B cells. Here, we tested the immunological and virological effects of
      PD-1 blockade combined with antiretroviral therapy (ART) in rhesus macaques.
      Administration of anti-PD-1 antibody 10 days prior to ART initiation rapidly
      enhanced antiviral CD8+ T cell function and diminished IFN-stimulated genes. This
      resulted in faster viral suppression in plasma and better Th17 cell
      reconstitution in the rectal mucosa following ART initiation. PD-1 blockade
      during ART resulted in lower levels of cell-associated replication-competent
      virus. Following ART interruption, PD-1 antibody-treated animals showed markedly
      higher expansion of proliferating CXCR5+perforin+granzyme B+ effector CD8+ T
      cells and lower regulatory T cells that resulted in better control of viremia.
      Our results show that PD-1 blockade can be administered safely with ART to
      augment antiviral CD8+ T cell function and reduce the viral reservoir, leading to
      improved control of viral rebound after ART interruption.

PMID- 30232274
TI  - The evolving relationship of wound healing and tumor stroma.
AB  - The stroma in solid tumors contains a variety of cellular phenotypes and
      signaling pathways associated with wound healing, leading to the concept that a
      tumor behaves as a wound that does not heal. Similarities between tumors and
      healing wounds include fibroblast recruitment and activation, extracellular
      matrix (ECM) component deposition, infiltration of immune cells,
      neovascularization, and cellular lineage plasticity. However, unlike a wound that
      heals, the edges of a tumor are constantly expanding. Cell migration occurs both
      inward and outward as the tumor proliferates and invades adjacent tissues, often
      disregarding organ boundaries. The focus of our review is cancer associated
      fibroblast (CAF) cellular heterogeneity and plasticity and the acellular matrix
      components that accompany these cells. We explore how similarities and
      differences between healing wounds and tumor stroma continue to evolve as
      research progresses, shedding light on possible therapeutic targets that can
      result in innovative stromal-based treatments for cancer.

PMID- 30232278
TI  - Long-term remission despite clonal expansion of replication-competent HIV-1
      isolates.
AB  - Clonal expansion of T cells harboring replication-competent virus has recently
      been demonstrated in patients on suppressive antiretroviral therapy (ART)
      regimens. However, there has not been direct evidence of this phenomenon in
      settings of natural control, including in posttreatment controllers who maintain
      control of viral replication after treatment when ART is discontinued. We present
      a case of an individual who has had undetectable viral loads for more than 15
      years following the cessation of ART. Using near-full-genome sequence analysis,
      we demonstrate that 9 of 12 replication-competent isolates cultured from this
      subject were identical and that this identity was maintained 6 months later. A
      similar pattern of replication-competent virus clonality was seen in a treatment
      naive HLA-B*57 elite controller. In both cases, we show that CD8+ T cells are
      capable of suppressing the replication of the clonally expanded viruses in vitro.
      Our data suggest that, while clonal expansion of replication-competent virus can
      present a barrier to viral eradication, these viral isolates remain susceptible
      to HIV-specific immune responses and can be controlled in patients with long-term
      suppression of viral replication.

PMID- 30232279
TI  - Neutrophil accumulation and NET release contribute to thrombosis in HIT.
AB  - Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenic
      disorder associated with a severe prothrombotic state. We investigated whether
      neutrophils and neutrophil extracellular traps (NETs) contribute to the
      development of thrombosis in HIT. Using an endothelialized microfluidic system
      and a murine passive immunization model, we show that HIT induction leads to
      increased neutrophil adherence to venous endothelium. In HIT mice, endothelial
      adherence is enhanced immediately downstream of nascent venous thrombi, after
      which neutrophils undergo retrograde migration via a CXCR2-dependent mechanism to
      accumulate into the thrombi. Using a microfluidic system, we found that PF4 binds
      to NETs, leading them to become compact and DNase resistant. PF4-NET complexes
      selectively bind HIT antibodies, which further protect them from nuclease
      digestion. In HIT mice, inhibition of NET formation through Padi4 gene disruption
      or DNase treatment limited venous thrombus size. PAD4 inactivation did affect
      arterial thrombi or severity of thrombocytopenia in HIT. Thus, neutrophil
      activation contributes to the development of venous thrombosis in HIT by
      enhancing neutrophil-endothelial adhesion and neutrophil clot infiltration, where
      incorporated PF4-NET-HIT antibody complexes lead to thrombosis propagation.
      Inhibition of neutrophil endothelial adhesion, prevention of neutrophil chemokine
      dependent recruitment of neutrophils to thrombi, or suppression of NET release
      should be explored as strategies to prevent venous thrombosis in HIT.

PMID- 30232280
TI  - Imbalance of immunological synapse-kinapse states reflects tumor escape to
      immunity in glioblastoma.
AB  - Since the proper activation of T cells requires the physical interaction with
      target cells through the formation of immunological synapses (IS), an alteration
      at this level could be a reason why tumors escape the immune response. As part of
      their life cycle, it is thought that T cells alternate between a static phase,
      the IS, and a dynamic phase, the immunological kinapse (IK), depending on high or
      low antigen sensing. Our investigation performed in tissue samples of human
      glioma shows that T cells are able to establish synapsing interactions not only
      with glioma tumorigenic cells, but also with stromal myeloid cells. Particularly,
      the IS displaying a T cell receptor-rich (TCR-rich) central supramolecular
      activation cluster (cSMAC) is preferentially established with stromal cells, as
      opposed to malignant cells. Conversely, T cells in the malignant areas showed
      distinct morphometric parameters compared with nonneoplastic tissue - the former
      characterized by an elongated shape, well-suited to kinaptic dynamics.
      Importantly, high-resolution 3-dimensional analyses demonstrated the existence of
      bona-fide IK preferentially arranged in malignant areas of the tumor. This
      imbalance of IS/IK states between these 2 microenvironments reveals the low
      antigenic sensing of T cells when patrolling tumorigenic cells and reflects the
      immunoevasive environment of the tumor.

PMID- 30232281
TI  - 4-1BB enhancement of CAR T function requires NF-kappaB and TRAFs.
AB  - Chimeric antigen receptors (CARs) have an antigen-binding domain fused to
      transmembrane, costimulatory, and CD3zeta domains. Two CARs with regulatory
      approval include a CD28 or 4-1BB costimulatory domain. While both CARs achieve
      similar clinical outcomes, biologic differences have become apparent but not
      completely understood. Therefore, in this study we aimed to identify mechanistic
      differences between 4-1BB and CD28 costimulation that contribute to the biologic
      differences between the 2 CARs and could be exploited to enhance CAR T cell
      function. Using CD19-targeted CAR T cells with 4-1BB we determined that
      enhancement of T cell function is driven by NF-kappaB. Comparison to CAR T cells
      with CD28 also revealed that 4-1BB is associated with more antiapoptotic proteins
      and dependence on persistence for B cell killing. While TNF receptor-associated
      factor 2 (TRAF2) has been presupposed to be required for 4-1BB costimulation in
      CAR T cells, we determined that TRAF1 and TRAF3 are also critical. We observed
      that TRAFs impacted CAR T viability and proliferation, as well as cytotoxicity
      and/or cytokines, in part by regulating NF-kappaB. Our study demonstrates how 4
      1BB costimulation in CAR T cells impacts antitumor eradication and clinical
      outcomes and has implications for enhanced CAR design.

PMID- 30232282
TI  - A limb-girdle muscular dystrophy 2I model of muscular dystrophy identifies
      corrective drug compounds for dystroglycanopathies.
AB  - Zebrafish are a powerful tool for studying muscle function owing to their high
      numbers of offspring, low maintenance costs, evolutionarily conserved muscle
      functions, and the ability to rapidly take up small molecular compounds during
      early larval stages. Fukutin-related protein (FKRP) is a putative protein
      glycosyltransferase that functions in the Golgi apparatus to modify sugar chain
      molecules of newly translated proteins. Patients with mutations in the FKRP gene
      can have a wide spectrum of clinical symptoms with varying muscle, eye, and brain
      pathologies depending on the location of the mutation in the FKRP protein.
      Patients with a common L276I FKRP mutation have mild adult-onset muscle
      degeneration known as limb-girdle muscular dystrophy 2I (LGMD2I), whereas
      patients with more C-terminal pathogenic mutations develop the severe Walker
      Warburg syndrome (WWS)/muscle-eye-brain (MEB) disease. We generated fkrp-mutant
      zebrafish that phenocopy WWS/MEB pathologies including severe muscle breakdowns,
      head malformations, and early lethality. We have also generated a milder LGMD2I
      model zebrafish via overexpression of a heat shock-inducible human FKRP (L276I)
      transgene that shows milder muscle pathology. Screening of an FDA-approved drug
      compound library in the LGMD2I zebrafish revealed a strong propensity towards
      steroids, antibacterials, and calcium regulators in ameliorating FKRP-dependent
      pathologies. Together, these studies demonstrate the utility of the zebrafish to
      both study human-specific FKRP mutations and perform compound library screenings
      for corrective drug compounds to treat muscular dystrophies.

PMID- 30232283
TI  - Chronic infection stunts macrophage heterogeneity and disrupts immune-mediated
      myogenesis.
AB  - The robust regenerative potential of skeletal muscle is imperative for the
      maintenance of tissue function across a host of potential insults including
      exercise, infection, and trauma. The highly coordinated action of multiple immune
      populations, especially macrophages, plays an indispensable role in guiding this
      reparative program. However, it remains unclear how skeletal muscle repair
      proceeds in a chronically inflamed setting, such as infection, where an active
      immune response is already engaged. To address this question, we used a
      cardiotoxin injury model to challenge the reparative potential of chronically
      infected muscle. Compared with regenerating naive skeletal muscle, infected
      skeletal muscle exhibited multiple indicators of delayed muscle repair including
      a divergent morphologic response to injury and dysregulated expression of
      myogenic regulatory factors. Further, using both flow cytometric and single-cell
      RNA sequencing approaches, we show that reduced macrophage heterogeneity due to
      delayed emergence of restorative subsets underlies dysfunctional tissue repair
      during chronic infection. Our findings highlight how the preexisting inflammatory
      environment within tissue alters reparative immunity and ultimately the quality
      of tissue regeneration.

PMID- 30232285
TI  - Necroptosis of infiltrated macrophages drives Yersinia pestis dispersal within
      buboes.
AB  - When draining lymph nodes become infected by Yersinia pestis (Y. pestis), a
      massive influx of phagocytic cells occurs, resulting in distended and necrotic
      structures known as buboes. The bubonic stage of the Y. pestis life cycle
      precedes septicemia, which is facilitated by trafficking of infected mononuclear
      phagocytes through these buboes. However, how Y. pestis convert these immunocytes
      recruited by host to contain the pathogen into vehicles for bacterial dispersal
      and the role of immune cell death in this context are unknown. We show that the
      lymphatic spread requires Yersinia outer protein J (YopJ), which triggers death
      of infected macrophages by downregulating a suppressor of receptor-interacting
      protein kinase 1-mediated (RIPK1-mediated) cell death programs. The YopJ
      triggered cell death was identified as necroptotic, which released intracellular
      bacteria, allowing them to infect new neighboring cell targets. Dying macrophages
      also produced chemotactic sphingosine 1-phosphate, enhancing cell-to-cell
      contact, further promoting infection. This necroptosis-driven expansion of
      infected macrophages in buboes maximized the number of bacteria-bearing
      macrophages reaching secondary lymph nodes, leading to sepsis. In support,
      necrostatins confined bacteria within macrophages and protected mice from lethal
      infection. These findings define necrotization of buboes as a mechanism for
      bacterial spread and a potential target for therapeutic intervention.

PMID- 30232284
TI  - Abnormal neutrophil signature in the blood and pancreas of presymptomatic and
      symptomatic type 1 diabetes.
AB  - BACKGROUND: Neutrophils and their inflammatory mediators are key pathogenic
      components in multiple autoimmune diseases, while their role in human type 1
      diabetes (T1D), a disease that progresses sequentially through identifiable
      stages prior to the clinical onset, is not well understood. We previously
      reported that the number of circulating neutrophils is reduced in patients with
      T1D and in presymptomatic at-risk subjects. The aim of the present work was to
      identify possible changes in circulating and pancreas-residing neutrophils
      throughout the disease course to better elucidate neutrophil involvement in human
      T1D. METHODS: Data collected from 389 subjects at risk of developing T1D, and
      enrolled in 4 distinct studies performed by TrialNet, were analyzed with
      comprehensive statistical approaches to determine whether the number of
      circulating neutrophils correlates with pancreas function. To obtain a broad
      analysis of pancreas-infiltrating neutrophils throughout all disease stages,
      pancreas sections collected worldwide from 4 different cohorts (i.e., nPOD,
      DiViD, Siena, and Exeter) were analyzed by immunohistochemistry and
      immunofluorescence. Finally, circulating neutrophils were purified from unrelated
      nondiabetic subjects and donors at various T1D stages and their transcriptomic
      signature was determined by RNA sequencing. RESULTS: Here, we show that the
      decline in beta cell function is greatest in individuals with the lowest
      peripheral neutrophil numbers. Neutrophils infiltrate the pancreas prior to the
      onset of symptoms and they continue to do so as the disease progresses. Of
      interest, a fraction of these pancreas-infiltrating neutrophils also extrudes
      neutrophil extracellular traps (NETs), suggesting a tissue-specific pathogenic
      role. Whole-transcriptome analysis of purified blood neutrophils revealed a
      unique molecular signature that is distinguished by an overabundance of IFN
      associated genes; despite being healthy, said signature is already present in T1D
      autoantibody-negative at-risk subjects. CONCLUSIONS: These results reveal an
      unexpected abnormality in neutrophil disposition both in the circulation and in
      the pancreas of presymptomatic and symptomatic T1D subjects, implying that
      targeting neutrophils might represent a previously unrecognized therapeutic
      modality. FUNDING: Juvenile Diabetes Research Foundation (JDRF), NIH, Diabetes
      UK.

PMID- 30232286
TI  - Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid
      during virologically suppressed HIV.
AB  - Central nervous system (CNS) immune activation is an important driver of neuronal
      injury during several neurodegenerative and neuroinflammatory diseases. During
      HIV infection, CNS immune activation is associated with high rates of
      neurocognitive impairment, even during sustained long-term suppressive
      antiretroviral therapy (ART). However, the cellular subsets that drive immune
      activation and neuronal damage in the CNS during HIV infection and other
      neurological conditions remain unknown, in part because CNS cells are difficult
      to access in living humans. Using single-cell RNA sequencing (scRNA-seq) on
      cerebrospinal fluid (CSF) and blood from adults with and without HIV, we
      identified a rare (<5% of cells) subset of myeloid cells that are found only in
      CSF and that present a gene expression signature that overlaps significantly with
      neurodegenerative disease-associated microglia. This highlights the power of
      scRNA-seq of CSF to identify rare CNS immune cell subsets that may perpetuate
      neuronal injury during HIV infection and other conditions.

PMID- 30232287
TI  - Haptoglobin improves shock, lung injury, and survival in canine pneumonia.
AB  - During the last half-century, numerous antiinflammatory agents were tested in
      dozens of clinical trials and have proven ineffective for treating septic shock.
      The observation in multiple studies that cell-free hemoglobin (CFH) levels are
      elevated during clinical sepsis and that the degree of increase correlates with
      higher mortality suggests an alternative approach. Human haptoglobin binds CFH
      with high affinity and, therefore, can potentially reduce iron availability and
      oxidative activity. CFH levels are elevated over approximately 24-48 hours in our
      antibiotic-treated canine model of S. aureus pneumonia that simulates the
      cardiovascular abnormalities of human septic shock. In this 96-hour model,
      resuscitative treatments, mechanical ventilation, sedation, and continuous care
      are translatable to management in human intensive care units. We found, in this
      S. aureus pneumonia model inducing septic shock, that commercial human
      haptoglobin concentrate infusions over 48-hours bind canine CFH, increase CFH
      clearance, and lower circulating iron. Over the 96-hour study, this treatment was
      associated with an improved metabolic profile (pH, lactate), less lung injury,
      reversal of shock, and increased survival. Haptoglobin binding compartmentalized
      CFH to the intravascular space. This observation, in combination with increasing
      CFHs clearance, reduced available iron as a potential source of bacterial
      nutrition while decreasing the ability for CFH and iron to cause extravascular
      oxidative tissue injury. In contrast, haptoglobin therapy had no measurable
      antiinflammatory effect on elevations in proinflammatory C-reactive protein and
      cytokine levels. Haptoglobin therapy enhances normal host defense mechanisms in
      contrast to previously studied antiinflammatory sepsis therapies, making it a
      biologically plausible novel approach to treat septic shock.

PMID- 30232288
TI  - Essential role of IFN-gamma in T cell-associated intestinal inflammation.
AB  - Paneth cells contribute to small intestinal homeostasis by secreting
      antimicrobial peptides and constituting the intestinal stem cell (ISC) niche.
      Certain T cell-mediated enteropathies are characterized by extensive Paneth cell
      depletion coincident with mucosal destruction and dysbiosis. In this study,
      mechanisms of intestinal crypt injury have been investigated by characterizing
      responses of mouse intestinal organoids (enteroids) in coculture with mouse T
      lymphocytes. Activated T cells induced enteroid damage, reduced Paneth cell and
      Lgr5+ ISC mRNA levels, and induced Paneth cell death through a caspase-3/7
      dependent mechanism. IFN-gamma mediated these effects, because IFN-gamma receptor
      null enteroids were unaffected by activated T cells. In mice, administration of
      IFN-gamma induced enteropathy with crypt hyperplasia, villus shortening, Paneth
      cell depletion, and modified ISC marker expression. IFN-gamma exacerbated
      radiation enteritis, which was ameliorated by treatment with a selective JAK1/2
      inhibitor. Thus, IFN-gamma induced Paneth cell death and impaired regeneration of
      small intestinal epithelium in vivo, suggesting that IFN-gamma may be a useful
      target for treating defective mucosal regeneration in enteric inflammation.

PMID- 30232289
TI  - Gluconeogenesis and risk for fasting hyperglycemia in Black and White women.
AB  - Black women, compared with White women, have high rates of whole-body insulin
      resistance but a lower prevalence of fasting hyperglycemia and hepatic steatosis.
      This dissociation of whole-body insulin resistance from fasting hyperglycemia may
      be explained by racial differences in gluconeogenesis, hepatic fat, or tissue
      specific insulin sensitivity. Two groups of premenopausal federally employed
      women, without diabetes were studied. Using stable isotope tracers, [2H2O] and
      [6,62-H2]glucose, basal glucose production was partitioned into its components
      (gluconeogenesis and glycogenolysis) and basal whole-body lipolysis
      ([2H5]glycerol) was measured. Indices of insulin sensitivity, whole-body (SI),
      hepatic (HISIGPR), and adipose tissue, were calculated. Hepatic fat was measured
      by proton magnetic resonance spectroscopy. Black women had less hepatic fat and
      lower fractional and absolute gluconeogenesis. Whole-body SI, HISIGPR, and
      adipose tissue sensitivity were similar by race, but at any given level of whole
      body SI, Black women had higher HISIGPR. Therefore, fasting hyperglycemia may be
      a less common early pathological feature of prediabetes in Black women compared
      with White women, because gluconeogenesis remains lower despite similar whole
      body SI.

PMID- 30232292
TI  - MicroRNA-377 Inhibits Atherosclerosis by Regulating Triglyceride Metabolism
      Through the DNA Methyltransferase 1 in Apolipoprotein E-Knockout Mice.
AB  - BACKGROUND: Lipoprotein lipase (LPL) plays an important role in triglyceride
      metabolism. It is translocated across endothelial cells to reach the luminal
      surface of capillaries by glycosylphosphatidylinositol-anchored high-density
      lipoprotein binding protein 1 (GPIHBP1), where it hydrolyzes triglycerides in
      lipoproteins. MicroRNA 377 (miR-377) is highly associated with lipid levels.
      However, how miR-377 regulates triglyceride metabolism and whether it is involved
      in the development of atherosclerosis remain largely unexplored. Methods and
      Results: The clinical examination displayed that miR-377 expression was markedly
      lower in plasma from patients with hypertriglyceridemia compared with non
      hypertriglyceridemic subjects. Bioinformatics analyses and a luciferase reporter
      assay showed that DNA methyltransferase 1 (DNMT1) was a target gene of miR-377.
      Moreover, miR-377 increased LPL binding to GPIHBP1 by directly targeting DNMT1 in
      human umbilical vein endothelial cells (HUVECs) and apolipoprotein E (ApoE)
      knockout (KO) mice aorta endothelial cells (MAECs). In vivo, hematoxylin-eosin
      (H&E), Oil Red O and Masson's trichrome staining showed that ApoE-KO mice treated
      with miR-377 developed less atherosclerotic plaques, accompanied by reduced
      plasma triglyceride levels. CONCLUSIONS: It is concluded that miR-377 upregulates
      GPIHBP1 expression, increases the LPL binding to GPIHBP1, and reduces plasma
      triglyceride levels, likely through targeting DNMT1, inhibiting atherosclerosis
      in ApoE-KO mice.

PMID- 30232290
TI  - Microbiota-sensitive epigenetic signature predicts inflammation in Crohn's
      disease.
AB  - Altered response to the intestinal microbiota strongly associates with
      inflammatory bowel disease (IBD); however, how commensal microbial cues are
      integrated by the host during the pathogenesis of IBD is not understood.
      Epigenetics represents a potential mechanism that could enable intestinal
      microbes to modulate transcriptional output during the development of IBD. Here,
      we reveal a histone methylation signature of intestinal epithelial cells isolated
      from the terminal ilea of newly diagnosed pediatric IBD patients. Genes
      characterized by significant alterations in histone H3-lysine 4 trimethylation
      (H3K4me3) showed differential enrichment in pathways involving immunoregulation,
      cell survival and signaling, and metabolism. Interestingly, a large subset of
      these genes was epigenetically regulated by microbiota in mice and several
      microbiota-sensitive epigenetic targets demonstrated altered expression in IBD
      patients. Remarkably though, a substantial proportion of these genes exhibited
      H3K4me3 levels that correlated with the severity of intestinal inflammation in
      IBD, despite lacking significant differential expression. Collectively, these
      data uncover a previously unrecognized epigenetic profile of IBD that can be
      primed by commensal microbes and indicate sensitive targets in the epithelium
      that may underlie how microbiota predispose to subsequent intestinal inflammation
      and disease.

PMID- 30232294
TI  - Management goals by patient category.

PMID- 30232293
TI  - Platypnea-Orthodeoxia Syndrome Due to Atrial Septal Defect and Combined Thoracic
      Deformities in a Young Woman.

PMID- 30232291
TI  - Antioxidant metabolism regulates CD8+ T memory stem cell formation and antitumor
      immunity.
AB  - Adoptive T cell transfer (ACT) immunotherapy benefits from early differentiated
      stem cell memory T (Tscm) cells capable of persisting in the long term and
      generating potent antitumor effectors. Due to their paucity ex vivo, Tscm cells
      can be derived from naive precursors, but the molecular signals at the basis of
      Tscm cell generation are ill-defined. We found that less differentiated human
      circulating CD8+ T cells display substantial antioxidant capacity ex vivo
      compared with more differentiated central and effector memory T cells. Limiting
      ROS metabolism with antioxidants during naive T cell activation hindered terminal
      differentiation, while allowing expansion and generation of Tscm cells. N
      acetylcysteine (NAC), the most effective molecule in this regard, induced
      transcriptional and metabolic programs characteristic of self-renewing memory T
      cells. Upon ACT, NAC-generated Tscm cells established long-term memory in vivo
      and exerted more potent antitumor immunity in a xenogeneic model when redirected
      with CD19-specific CAR, highlighting the translational relevance of NAC as a
      simple and inexpensive method to improve ACT.

PMID- 30232295
TI  - To the Editor: Current Status of CDC Lipid Standardization and International
      Needs for Standardization in Epidemiological Studies and Clinical Trials in Japan
      Response: Standardization of the measurement of serum lipids - Looking back at 30
      years of experience in clinical laboratories.

PMID- 30232296
TI  - In Memoriam: Yuichiro Goto, MD (October 6, 1992 - May 28, 2003).

PMID- 30232297
TI  - Unilateral Chewing as a Risk Factor for Hearing Loss: Association between Chewing
      Habits and Hearing Acuity.
AB  - Hearing loss is a common disease in older adults. In order to lower the
      prevalence of hearing loss, it is important to identify its risk factors.
      Although some studies have found a relationship between dental status and hearing
      acuity, few studies have investigated the relationship between unilateral chewing
      and hearing acuity. This study aimed to assess the effects of unilateral chewing
      on hearing acuity, with a focus on the risk of hearing loss. Eighty-one
      participants (aged 51-87 years) were included in the present study. Their chewing
      habits were determined by visual inspection. The participants were divided into
      two groups: the Unilateral Chewing Group (UCG; n = 43) and the Bilateral Chewing
      Group (BCG; n = 38). The preferred chewing side was identified for the UCG.
      Hearing acuity was determined using pure tone audiometry in a noise-free chamber,
      conducted at frequencies of 500, 1,000, 2,000, and 4,000 Hz. Hearing loss was
      defined as a lower hearing threshold greater than 50 dB in either ear at any
      frequency. Mean hearing thresholds at frequencies of 2,000 and 4,000 Hz were
      significantly higher, by 5.12 and 15.75 dB, respectively, for the UCG compared to
      the BCG (P < 0.05). The UCG had a 3.78-fold higher likelihood of suffering from
      hearing loss (95% confidence interval [CI]: 1.81-7.88). The results suggest that
      bilateral chewing could be beneficial for preventing hearing loss. This study may
      provide evidence to support clinical interventions aimed at reducing the risk of
      hearing loss in patients with unilateral chewing habits.

PMID- 30232298
TI  - Single-Center Experience with Minimally Invasive Mitral Operations through Right
      Minithoracotomy.
AB  - BACKGROUND: To report single-institution experience with minimally invasive
      mitral valve operations through the right minithoracotomy over a 5-year period.
      METHODS: Patients who underwent minimally invasive mitral valve surgery (MIMVS)
      between January 2012 and December 2016 were included. Clinical follow-up data
      were collected in a prospective database and analyzed retrospectively. RESULTS:
      Data from 151 patients were assessed (mean age, 63.4 +/- 9.7 years; 55% were
      females). Overall 30-day mortality was 0.7% (n = 1). Mean operating time,
      cardiopulmonary bypass, and aortic cross-clamp times were 254.9 +/- 48.7, 140.5
      +/- 36.1, and 94.8 +/- 27.0 minutes, respectively. Associated procedures were
      tricuspid valve annuloplasty (37.1%, n = 56) and closure of atrial septal defect
      (6.0%, n = 9). Cryoablation was performed in 43.7% of patients (n = 66). One
      patient (0.7%) required conversion to median sternotomy and six patients (4.0%)
      underwent re-explorations due to bleeding. Median postoperative hospital stay was
      12 days. Overall survival at 5 years was 94.1% +/- 2.0%. Freedom from reoperation
      was 94.6% +/- 2.9% at 5 years. CONCLUSIONS: MIMVS is a feasible, safe, and
      reproducible approach with low mortality and morbidity. Mitral valve surgery
      through a small thoracotomy is a good alternative to conventional surgical
      access.

PMID- 30232299
TI  - [Activities of Japanese Occupational Health Service Centers].
AB  - OBJECTIVES: Although both occupational health centers and occupational health
      service centers (OHSCs) support small-scale enterprises in Japan, the activities
      of OHSCs are not well detailed. This survey aimed to clarify the activities and
      subjective evaluation by directors and coordinators of OHSCs, with a focus on
      improving occupational health services in small-scale enterprises. METHODS: The
      survey was conducted by mailing questionnaires to 377 directors and 507
      coordinators at 344 OHSCs in Japan from September 2016 to January 2017. The
      survey items comprised questions about director and coordinator characteristics,
      OHSCs' systems and activities, and subjective evaluations of OHSCs' activities.
      RESULTS: Responses were obtained from 290 directors (76.9%) and 413 coordinators
      (81.5%) of OHSCs. Of the directors, 66.2% were occupational health directors of
      medical associations. The average number of years' experience for coordinators
      was 5.7 years, and 44.6% were specially qualified, most as health officers. The
      percentage of OHSC staff who were not coordinators was 22%, and 29.8% of OHSCs
      had a public health nurse. The Office of Labor Standard's guidance was most often
      cited as the reason why small-scale enterprises decided to use OHSCs. At least
      90% of OHSC directors and coordinators evaluated OHSCs' activities as "good".
      Directors not consulted by a coordinator evaluated OHSCs' activities as "very
      good" significantly more often than directors who were consulted by a coordinator
      (p<.001). Similarly, directors not consulted by occupational health centers'
      members evaluated OHSCs' activities as "very good" significantly more often than
      directors who were consulted by occupational health centers' members (p<.006).
      Coordinators who were in charge of two or more regions medical associations
      evaluated OHSCs' activities as "very good" significantly more often than those
      who were in charge of only one regions medical association (p=.014).Coordinators
      who had qualification of occupational health evaluated OHSCs' activities as "very
      good" significantly more often than coordinators who had not (p=.007).
      Coordinators who conducted public relations activities evaluated OHSCs'
      activities as "very good" significantly more often than those who did not
      (p=.011). Similarly, coordinators who conducted public relations activities via
      email and homepage promotions evaluated OHSCs' activities as "very good"
      significantly more often than those who did not (p<.001). In addition,
      coordinators who used the consultation record evaluated OHSCs' activities as
      "very good" significantly more often than those who did not (p<.001), whereas
      coordinators who consulted with a director evaluated OHSCs' activities as "very
      good" significantly more often than those who did not (p=.028). Coordinators who
      thought doctors were fit for the OHSCs' activities had significantly higher
      percentages of qualifications than those who did not think this way (p=.032).
      Likewise, coordinators who conducted public relations activities had
      significantly higher percentages of qualifications than those who did not
      (p<.001), whereas coordinators who used the consultation record had significantly
      higher percentages of qualifications than those who did not (p=.006).
      CONCLUSIONS: This survey clarified OHSCs' activities and suggested that systems
      and activities are not the same across OHSCs. We found that coordinators need to
      master knowledge of occupational health and work support. In addition, improving
      the relationship between directors and coordinators, enhancing public relations
      activities, and utilizing tools such as a chart improved OHSCs' activities.

PMID- 30232300
TI  - A case of ectopic ACTH syndrome due to DDAVP-sensitive but V1b receptor-negative
      bronchial typical carcinoid with lymphatic metastasis and plasma ProGRP
      elevation.
AB  - Ectopic ACTH syndrome (EAS) is a potentially fatal endocrine disease that results
      from a variety of neuroendocrine tumors (NETs), such as small cell lung cancer
      (SCLC) and bronchial typical carcinoid. Typical carcinoid is usually slow
      growing, not associated with plasma progastrin releasing peptide (ProGRP)
      elevation. Here, we report a 47-year-old female smoker with progressive typical
      carcinoid and plasma ProGRP elevation. Several types of Cushingoid features were
      found on physical examination. In addition, laboratory examination showed
      elevated plasma ACTH and serum cortisol levels. These findings indicated ACTH
      dependent Cushing's syndrome. Moreover, the serum cortisol level was not
      suppressed by overnight high-dose dexamethasone treatment, suggesting the
      presence of an extra-pituitary tumor. Contrast-enhanced brain MRI revealed no
      pituitary adenoma, which also supported the idea that EAS occurred in the present
      case. Strikingly, chest computed tomographic (CT) scan showed a single 18-mm
      peripheral nodule in the right middle lobe of the lung. Tumor marker analysis
      revealed an elevation in plasma ProGRP. These data suggested a possibility that
      SCLC secreted ACTH and caused EAS in this patient. Of note, the plasma ACTH level
      was increased (1.7 fold) in l-desamino-8-D-arginine vasopressin (DDAVP) test,
      also suggesting the specific clinical feature in this case. After additional
      imaging examinations, we performed surgical resection with the suspicion of
      limited SCLC. As a result, pathological examination revealed a vasopressin
      receptor Ib (V1b) receptor-negative bronchial typical carcinoid with ACTH
      production and mediastinal lymphatic metastasis. In summary, we present a case of
      EAS caused by progressive bronchial typical carcinoid with plasma ProGRP
      elevation. We propose a novel subtype of lung typical carcinoid.

PMID- 30232301
TI  - Needs survey on the priority given to periodical medical examination items among
      occupational physicians in Japan.
AB  - OBJECTIVES: To clarify the priority given to periodical medical examination items
      among occupational physicians in Japan. METHODS: Sixty-two occupational
      physicians who participated in this study selected statutory and non-statutory
      items within two types of budget plans: one lower (8,500 yen) than the total fee
      of statutory medical examinations (9,250 and 11,290 yen), and the other higher
      (12,000 yen) than the total fee. Medical fee points were used to set the cost of
      each medical examination item. A three round Delphi method was used from May to
      July 2016 to clarify the consensus opinion of occupational physicians. RESULTS:
      The statutory items (selection rate: between 66 and 100%), except for waist
      circumference (15%) and sputum examination (0%), and serum creatinine (58%, non
      statutory item) were included in the smaller budget plan (8,500 yen). In the
      larger budget plan (12,000 yen), the statutory items (selection rate: between 92
      and 100%), except for waist circumference (39%) and sputum examination (0%), and
      some non-statutory items, namely serum creatinine (95%), leukocytes (92%), uric
      acid (89%), and fecal occult blood reaction (81%), had a selection rate over 80%.
      In addition, statutory items with higher accuracy were preferred, which included
      the following: air conduction pure-tone audiometry (92%), imaging diagnosis of
      thoracic X-ray examinations by a specialist (97%), glycated hemoglobin levels
      (98%), and electrocardiogram assessment by a specialist (100%). CONCLUSION: The
      statutory items, except for waist circumference and sputum examination, and some
      of the non-statutory items (e.g., serum creatinine) were given higher priority
      among occupational physicians in Japan.

PMID- 30232302
TI  - Combined cutting balloon and conventional balloon angioplasty in a dog with
      supravalvular pulmonary stenosis.
AB  - A 7-year-old Miniature Schnauzer presented with exercise intolerance and easy
      fatigability. Echocardiography revealed the presence of supravalvular pulmonary
      stenosis. The peak velocity through the stenosis was 6.4 m/sec, and the
      interventricular septum was flattened. Cutting balloon angioplasty was designed
      for the treatment of coronary artery stenosis, which was resistant to
      conventional balloon angioplasty. Accordingly, the dog underwent cutting balloon
      angioplasty and conventional balloon dilation. One month after treatment, it
      showed neither exercise intolerance nor easy fatigability. The ventricular septum
      flattening disappeared. Five months later, the dog showed an increase in
      activity. Two years later, the peak velocity through the stenosis decreased to
      4.4 m/sec. Neither clinical symptoms nor restenosis was observed. Thus,
      supravalvular pulmonary stenosis was successfully treated using this combination
      method. The present case showed that combined cutting balloon and conventional
      balloon angioplasty is a useful and minimally invasive treatment for
      supravalvular pulmonary stenosis.

PMID- 30232303
TI  - Short-term outcome of laparoscopic cholecystectomy for benign gall bladder
      diseases in 76 dogs.
AB  - Laparoscopic cholecystectomy (LC) is widely accepted as the standard treatment
      for benign gall bladder diseases in humans because it has proven to be less
      invasive and safer than are traditional methods. However, the efficacy of LC in
      dogs remains unclear. The present study aimed to examine the short-term outcome
      of LC for benign gall bladder diseases in dogs. We enrolled 76 consecutive dogs
      that underwent LC for benign gall bladder diseases at our hospital between April
      2008 and October 2016. Dogs with jaundice, gall bladder ruptures, abdominal
      effusion, or extrahepatic biliary obstruction were not excluded from the
      indication. Factors including age, body weight, sex, clinical sign, disease,
      operative time, conversion to open surgery, perioperative complications, and
      postoperative hospital stay were investigated. The median age of the dogs was 11
      years, and the median body weight was 5.4 kg. Fifty percent of the dogs exhibited
      no symptoms at the initial visit. Preoperative elevation of total bilirubin
      levels was observed in 16 dogs (21%). LC was successfully completed in 71 dogs
      (93%); the median operative time was 124 min. Although gall bladder ruptures were
      observed in 2 (2.6%) dogs, the operations were completed successfully. Three dogs
      (4.1%) had to be converted to open cholecystectomy and 2 (2.6%) underwent
      reoperation. Two dogs (2.6%) died intraoperatively and 2 (2.6%) died
      postoperatively. LC was a feasible, safe, and appropriate procedure considering
      the current operative indications for benign gall bladder diseases in dogs.

PMID- 30232305
TI  - [Chinese Journal of Nuclear Medicine and Molecular Imaging Volume 38, Number 8,
      August 25, 2018].

PMID- 30232306
TI  - Cubosomes as Oral Drug Delivery Systems: A Promising Approach for Enhancing the
      Release of Clopidogrel Bisulphate in the Intestine.
AB  - Clopidogrel bisulphate (CB) is a first line antiplatelet drug for treatment of
      myocardial infarction and stroke. Yet, its efficacy is limited by its poor
      solubility in intestinal pH, its main site of absorption. The main aim of this
      study is to enhance the intestinal release of CB by loading in cubosome
      nanoparticles. Glyceryl monooleate (GMO) based CB loaded cubosomes were prepared
      using a 33 factorial design to study the effect of polyvinyl alcohol (PVA),
      poloxamer 407 (PL407) concentrations and ratio of CB to the disperse phase on the
      average particle size, entrapment efficiency (%EE), in vitro release at 15 min
      (%Q15), and their morphology using transmission electron microscopy (TEM). The
      release of the optimized formula was compared in buffer transition media (pH 1.2
      for 2 h then pH 6.8 for 6 h) to free drug to study the effect of the changing pH
      in the gastrointestinal tract (GIT) on CB release. The antihaemostatic properties
      of the optimized formula were compared to the commercial product Plavix(r) using
      bleeding time (BT) model in rabbits. The prepared cubosomes were in the nano
      range (115+/-6.47 to 248+/-4.63 nm) with high %EE (91.22+/-4.09% to 98.98+/
      3.21%). The optimized formula showed significantly higher (p<0.05) CB release in
      intestinal pH and preserved the high% released (95.66+/-1.87%) in buffer
      transition release study compared to free drug (66.82+/-4.12%) as well as
      significantly (p<0.05) higher antihaemostatic properties with longer BT (628.47+/
      6.12 s) compared to Plavix(r) (412.43+/-7.97 s). Thus, cubosomes proved to be a
      successful platform to enhance the intestinal release of CB and improve its
      absorption.

PMID- 30232304
TI  - Rapid Detection of Avian Influenza A Virus (H7N9) by Lateral Flow Dipstick
      Recombinase Polymerase Amplification.
AB  - Avian influenza A (H7N9) virus has caused several epidemics and infection in both
      human and poultry. With mutation, the H7N9 virus gained its fifth endemic in
      China. Early diagnosis is crucial for the control of viral spread in poultry and
      prognosis of infected patients. In this study, we developed and evaluated a
      lateral flow dipstick recombinase polymerase amplification (LFD-RPA) assay for
      rapid detection of both hemagglutinin and neuraminidase gene of H7N9. Our H7-LFD
      RPA and N9-LFD-RPA assay were able to detect 32 fg H7N9 nucleic acid which is
      more convenient and rapid than previous methods. Through detecting 50 influenza
      positive samples, cross-reaction was not found with other subtypes of influenza
      virus. The 100% analytical specificity and sufficient analytical sensitivity
      results agreed the real time RT-PCR assay. The results data demonstrated that our
      method performed well and could be applied to the detection of H7N9 virus. This
      LFD-RPA assay provides a candidate method for rapid point-of-care diagnosis of
      H7N9.

PMID- 30232307
TI  - Rescue of the fetal damage associated with high intrauterine pressure by 17beta
      estradiol injection in ovariectomized progesterone-treated pregnant mice.
AB  - The present study examined the effects of progesterone (P) and 17beta-estradiol
      (E2) on fetal damage and intrauterine pressure in ovariectomized pregnant mice.
      The mice were ovariectomized on gestational day (GD) 9 (copulation plug = GD 0),
      and daily subcutaneous injection of various doses of P (2, 3 or 4 mg) or 4 mg P
      plus E2 (0.05 or 0.1 MUg) was given thereafter. Although P alone increased
      percentage of normal fetuses on GD 17 dose-dependently, fetal injury with
      edematous hematomata on their extremities was frequently observed. In the group
      treated with 4 mg P, the injured fetus was found at the highest percentage (18%)
      and intrauterine pressure was significantly higher than that in intact pregnant
      mice (controls). No injured fetus on GD 17 was found by the treatment with 4 mg P
      plus 0.05 or 0.1 MUg E2, and the treatments decreased the intrauterine pressure
      to the level of controls. Percentage of normal fetuses in the ovariectomized mice
      treated with 4 mg P plus 0.05 MUg E2 was similar to that of controls, while that
      in the ovariectomized mice treated with 4 mg P plus 0.1 MUg E2 markedly
      decreased. The results suggest that estrogen decreases intrauterine pressure to
      defend fetal damage in ovariectomized P-treated mice, and a high estrogen level
      interrupted pregnancy while keeping this estrogen action.

PMID- 30232308
TI  - [Participation/Dispatch Reports on International Conferences in 2018].

PMID- 30232310
TI  - [The Current Status of Standardizing Healthcare Information].

PMID- 30232309
TI  - [Dispatch Reports on Korean Society of Radiological Science Conference 2018
      (KSRSC 2018)].

PMID- 30232311
TI  - [Capillary Blood Flow of Muscle Before and After the Exercise Used by Intravoxel
      Incoherent Motion].
AB  - Capillaries are the most basic and important blood vessel of the circulatory
      systems. The evaluation of the blood flow may contribute to many studies in
      future. We evaluated the capillary blood flow change of lower limb muscle over
      time before and after the exercise used by magnetic resonance imaging-intravoxel
      incoherent motion (MRI-IVIM) obtained perfusion information. Furthermore, we
      examined an association between the muscle pain after the exercise and the
      diffusion weighted image (DWI) indexes. DWI was imaged using multi-b values for a
      thigh and calf muscles. MRI was performed just after an exercise test, 3, 6, and
      24 hours later, and the IVIM index and diffusion index were calculated.
      Furthermore, we interviewed the degree of the muscle ache 24 hours later. As a
      result, pseudo diffusion coefficient (D*) and f value as IVIM index increased
      after-exercise as compared with pre-exercise and decreased in 3 hours later. A
      similar tendency was found in the apparent diffusion coefficient and the
      diffusion coefficient as diffusion index. Furthermore, all indexes increased in
      after exercise from before exercise and decreased with time passed and increased
      again 24 hours later. In conclusion, IVIM could obtain capillary blood flow
      information, and it was suggested to contribute for sports medicine in future.

PMID- 30232312
TI  - [The Novel Evaluation Method of Geometric Distortion for 3D-MRI].
AB  - Recently, many imaging methods are developed in magnetic resonance imaging and in
      particular, the release of the 3D acquisition method is remarkable. The image
      distortion often becomes the problem by the gradient echo method and the echo
      planar imaging (EPI) -based method, but the image distortion of the 3D
      acquisition is not established. A purpose of this study is to examine the utility
      of the novel evaluation method of the image distortion for the 3D acquisition
      image. The spin echo image was used as a criteria image, and EPI was used as a
      target image for 3D acquisition imaging. Image J was used for the image
      processing. The value that divided the volume of the different shape of criteria
      image and the target image by the volume of the criteria image was defined as a
      distortion rate. Hence, we refer this method to the volume method. It is reported
      that the distortion rate of the EPI is proportional to a rectangle rate of
      rectangular field of view (RFOV). The distortion rate of the volume method for 50
      100% of rectangle ratio was compared with the theoretical value. In addition, the
      dependence by the threshold of the binarization was considered. Furthermore, the
      comparison with the NEMA (National Electrical Manufacturers Association) method
      was carried out. As a result, the distortion rate decreased according to a
      rectangular rate of RFOV by the volume method, and the numerical value was equal
      with a theoretical value. In addition, the distortion rate did not have the
      effect by the thresholding of binarizing. The volume method had less error of
      measurement than the NEMA method.

PMID- 30232314
TI  - [Seven Years after the Great East Japan Earthquake: Build Back Better and
      Radiological Science].

PMID- 30232313
TI  - [Proposal of Requirements Definition Method on Radiation Therapy Information
      System].
AB  - The troubles arising in the introduction of the medical information system are
      mostly related to the requirement definition. The present study proposed the
      requirements definition method on radiation therapy information system (RTIS) by
      using business modeling. The interview was conducted with six medical
      professionals regarding the entire business in the radiotherapy department. These
      businesses were modeled using Diamond Mandala Matrix (DMM) and data flow diagram
      (DFD) methods. Subsequently, functional requirements on RTIS were defined based
      on these modeling. As a result, 21 DMMs and 129 DFDs were created and 120
      functional requirements were defined. By defining the functional requirements of
      the users, mutual understanding with vendors will deepen, and avoid an expected
      trouble in introducing RTIS. DMM was effective as an initial modeling such as the
      interviews and the organization of businesses. DFD was also effective for the
      business improvement and the definition of system functional requirements.

PMID- 30232317
TI  - Erratum for "The protective effects of human umbilical cord mesenchymal stem
      cells on damaged ovarian function: A comparative study" by Zhang J et al.
      (BioScience Trends. 2016; 10(4):265-276).
AB  - It has come to the authors' attention that their article entitled "The protective
      effects of human umbilical cord mesenchymal stem cells on damaged ovarian
      function: A comparative study" (BioScience Trends. 2016; 10(4):265-276) included
      an error in Figure 4 (F, H). The corrected Figure 4 is printed below.

PMID- 30232315
TI  - Uric Acid and Risk of Atrial Fibrillation in the Korean General Population.
AB  - BACKGROUND: Increased serum uric acid is associated with prevalence and incidence
      of atrial fibrillation (AF), but there is a lack of studies on the association
      between serum uric acid and risk of AF in the general population. Methods and
      Results: We used the data from the Kangbuk Samsung Hospital health screening
      cohort recorded between 2002 and 2015. The primary outcome was incidence of AF
      diagnosed on 12-lead electrocardiography. We analyzed and compared the hazard
      ratios (HR) according to baseline serum uric acid quartiles. The present study
      involved 282,473 subjects without baseline AF. Mean follow-up was 5.4+/-3.6
      years. During follow-up, AF was identified in 365 subjects (cumulative incidence,
      0.13%). After multivariable adjustment, including that for C-reactive protein,
      the risk of AF was significantly higher in the upper 2 quartiles than in the
      lowest quartile in men (upper third quartile: adjusted HR, 1.53; 95% confidence
      interval [CI]: 1.11-2.89; highest quartile: HR, 1.60; 95% CI: 1.13-2.25). In
      women, even though AF incidence rate was very low (0.6 of 10,000 person-years),
      the risk of AF in the highest quartile was 6.93-fold that in the lowest quartile
      (95% CI: 1.53-31.29). CONCLUSIONS: Serum uric acid is significantly and
      positively associated with incident AF in the Korean general population.

PMID- 30232316
TI  - Canine spindle cell tumor mimicking human classical hemangiopericytoma.
AB  - The neoplastic mass developed in the left flank of a Border Collie dog. The tumor
      was resected surgically and evaluated histologically and immunohistochemically.
      Histologically a moderate number of spindle cells were proliferated with
      staghorn, placentoid, and myxoid growth patterns and a lack of perivascular
      whirling. Immunohistochemically, the tumor cells were positive to vimentin,
      laminin, S-100 protein, CD34 and CD117 antibodies. They were negative to
      cytokeratin AE1/3, desmin, alpha-SMA and calponin antibodies. Endothelial cells
      of the staghorn channels were positive for vWF antibody. The present case was
      diagnosed as spindle cell tumor, but it was similar to human classical
      hemangiopericytoma (HEP) and canine HEP classified by Avallon and others.

PMID- 30232318
TI  - Lactic Acidosis and Thrombocytopenia Associated with Linezolid Therapy: A Case
      Report.
AB  - BACKGROUND Linezolid (LZD) has been reported to combat several intractable
      infectious diseases, including multidrug-resistant infections and tuberculosis.
      Although quite a number of adverse effects of LZD therapy have been abundantly
      described so far, LZD associated lactic acidosis and thrombocytopenia have rarely
      been studied. We described a patient dying of lactic acidosis and
      thrombocytopenia associated with LZD therapy complications. To the best of our
      knowledge, this is the first report focusing on LZD therapy complications in
      treating patients with deadly abnormalities in hemogram. CASE REPORT A 50-year
      old Chinese female was diagnosed with endocarditis and thus received LZD therapy
      for 25 days, then complained about 6 days' abdominal pain and vomiting before
      being admitted to the Emergency Department. Upon admission, lactic acidosis and
      thrombocytopenia were immediately observed. CONCLUSIONS Physicians should be
      aware of typical clinical manifestations of lactic acidosis related to LZD
      exposure, since this complication might be a life-threatening metabolic
      emergency.

PMID- 30232319
TI  - Usability Study of the User-Interface of Intensive Care Ventilators Based on User
      Test and Eye-Tracking Signals.
AB  - BACKGROUND The aim of this study was to evaluate the ergonomics of the user
      interface for 3 intensive care ventilators, and identify usability problems
      leading to user errors. MATERIAL AND METHODS Sixteen respiratory therapists were
      recruited to perform 6 specific user-interface operational tasks on ventilators.
      Data (task completion time, pupil diameter, average slope of pupil diameter
      change, and subjective evaluation) were collected through objective measurement,
      questionnaires, and an eye-tracking instrument. RESULTS For task completion time,
      there were significant differences among ventilators in recognition tasks of
      ventilator mode and settings (P<0.05), modification of ventilator modes and
      recognizing (P<0.05) and changing alarm settings (P<0.05). A mean of 15+/-2 task
      failures was observed for each ventilator. For the change of pupil diameter, a
      significant difference was observed between ventilators (except task 2, P<0.05).
      For average slope of pupil diameter change, a significant difference was also
      observed between ventilators (except task 2, P<0.05). The Servo I showed a better
      correlation between task completion time and pupil diameter change. The
      subjective evaluation results were clear: Evital 4 received worst scores in terms
      of friendliness of user-interface, information display and safety (respectively,
      P<0.05). CONCLUSIONS The present study provided valuable evidence to indicate the
      ergonomic of ventilators now used in China. With the result of this study, we can
      infer that the Evital 4 were poorly ergonomic designed. Furthermore, the study
      also demonstrated that eye-tracking can be a promising tool to evaluate the
      ergonomics of the user-interface.

PMID- 30232320
TI  - Urinary biomarker panel for diagnosing patients with depression and anxiety
      disorders.
AB  - Available data indicate that patients with depression and anxiety disorders are
      likely to be at greater risk for suicide. Therefore, it is important to correctly
      diagnose patients with depression and anxiety disorders. However, there are still
      no empirical laboratory methods to objectively diagnose these patients. In this
      study, the multiple metabolomics platforms were used to profile the urine samples
      from 32 healthy controls and 32 patients with depression and anxiety disorders
      for identifying differential metabolites and potential biomarkers. Then, 16
      healthy controls and 16 patients with depression and anxiety disorders were used
      to independently validate the diagnostic performance of the identified
      biomarkers. Finally, a panel consisting of four biomarkers-N-methylnicotinamide,
      aminomalonic acid, azelaic acid and hippuric acid-was identified. This panel was
      capable of distinguishing patients with depression and anxiety disorders from
      healthy controls with an area under the receiver operating characteristic curve
      of 0.977 in the training set and 0.934 in the testing set. Meanwhile, we found
      that these identified differential metabolites were mainly involved in three
      metabolic pathways and five molecular and cellular functions. Our results could
      lay the groundwork for future developing a urine-based diagnostic method for
      patients with depression and anxiety disorders.

PMID- 30232321
TI  - The novel immunoglobulin super family receptor SLAMF9 identified in TAM of murine
      and human melanoma influences pro-inflammatory cytokine secretion and migration.
AB  - Melanoma is a highly immunogenic tumor with a good response to treatment with
      immune checkpoint inhibitors. Tumor-associated macrophages (TAMs) play an
      important immunosuppressive role in such tumors and have therefore been
      identified as possible future therapeutic targets in oncology. The aim of this
      study was to identify novel immunoregulatory receptors specifically expressed on
      TAM. Expression of Slamf9, a member of the signaling lymphocytic-activating
      molecule (Slam) immunoreceptor family, was found to be upregulated in a gene
      expression analysis of murine bone marrow-derived macrophages (BMDM) stimulated
      with tumor-conditioned medium of B16F1 melanoma cells. SLAMF9+ macrophages were
      identified in human and murine melanomas by using self-generated antibodies
      against human and murine SLAMF9. A comprehensive immunohistochemical analysis of
      tissue microarrays detected SLAMF9+ TAM in 73.3% of human melanomas, but also in
      95.5% of naevi of melanoma patients and in 50% of naevi from healthy controls. In
      addition, 20% of melanomas and 2.3% of naevi from melanoma patients displayed a
      positive SLAMF9 expression also in melanocytic cells. No SLAMF9 expression was
      detected in naevus cells of healthy donors. Although SLAMF9 has no intracellular
      signaling motif, a comprehensive functional analysis revealed that the molecule
      was able to significantly enhance TNF-alpha secretion after LPS-stimulation. In
      addition, SLAMF9 delayed the wound closure of RAW 264.7 cells in a scratch assay,
      while proliferation and cell death were not affected. Taken together, SLAMF9 is a
      novel type-I-transmembrane receptor with immunomodulatory properties in
      macrophages. Further studies are required to evaluate whether SLAMF9 classifies
      as a promising future therapeutic target in melanoma.

PMID- 30232322
TI  - Spermidine restores dysregulated autophagy and polyamine synthesis in aged and
      osteoarthritic chondrocytes via EP300.
AB  - Ageing is the primary risk factor for osteoarthritis (OA). A decline in the
      ageing-associated process of autophagy is suggested as a potential contributor to
      OA development. Polyamines such as spermidine decrease during ageing,
      contributing to impaired autophagy and reduced cellular function. However, the
      role of polyamines and their effect on the regulatory mechanism governing
      autophagy in aged and arthritic cartilage tissue has not been established.
      Elucidating if polyamine regulation of autophagy is impaired during ageing and OA
      in chondrocytes may lead to improved treatment approaches to protect against
      cartilage degradation. Our results indicate that polyamine synthesis was
      decreased in aged and OA cartilage, along with reduced autophagy activity,
      evidenced by decreased autophagy-related gene and protein expression and
      autophagosome formation. Importantly, spermidine treatment increased the
      expression of the acetyltransferase EP300, which binds to crucial autophagy
      proteins, Beclin1 and LC3, and elevates chondrocyte autophagy. Our data indicate
      spermidine prevents the ageing- and OA-related decrease in autophagy and may
      protect against OA development.

PMID- 30232323
TI  - Exceptional thermoelectric properties of flexible organic-inorganic hybrids with
      monodispersed and periodic nanophase.
AB  - Flexible organic-inorganic hybrids are promising thermoelectric materials to
      recycle waste heat in versatile formats. However, current organic/inorganic
      hybrids suffer from inferior thermoelectric properties due to aggregate
      nanostructures. Here we demonstrate flexible organic-inorganic hybrids where size
      tunable Bi2Te3 nanoparticles are discontinuously monodispersed in the continuous
      conductive polymer phase, completely distinct from traditional bi-continuous
      hybrids. Periodic nanofillers significantly scatter phonons while continuous
      conducting polymer phase provides favored electronic transport, resulting in
      ultrahigh power factor of ~1350 MUW m-1 K-2 and ultralow in-plane thermal
      conductivity of ~0.7 W m-1 K-1. Consequently, figure-of-merit (ZT) of 0.58 is
      obtained at room temperature, outperforming all reported organic materials and
      organic-inorganic hybrids. Thermoelectric properties of as-fabricated hybrids
      show negligible change for bending 100 cycles, indicating superior mechanical
      flexibility. These findings provide significant scientific foundation for shaping
      flexible thermoelectric functionality via synergistic integration of organic and
      inorganic components.

PMID- 30232324
TI  - Adaptation decorrelates shape representations.
AB  - Perception and neural responses are modulated by sensory history. Visual
      adaptation, an example of such an effect, has been hypothesized to improve
      stimulus discrimination by decorrelating responses across a set of neural units.
      While a central theoretical model, behavioral and neural evidence for this theory
      is limited and inconclusive. Here, we use a parametric 3D shape-space to test
      whether adaptation decorrelates shape representations in humans. In a behavioral
      experiment with 20 subjects, we find that adaptation to a shape class improves
      discrimination of subsequently presented stimuli with similar features. In a BOLD
      fMRI experiment with 10 subjects, we observe that adaptation to a shape class
      decorrelates the multivariate representations of subsequently presented stimuli
      with similar features in object-selective cortex. These results support the long
      standing proposal that adaptation improves perceptual discrimination and
      decorrelates neural representations, offering insights into potential underlying
      mechanisms.

PMID- 30232326
TI  - Sounding-rocket microgravity experiments on alumina dust.
AB  - Alumina (Al2O3) is believed to be the first major condensate to form in the gas
      outflow from oxygen-rich evolved stars because of the refractoriness and that
      alpha-Al2O3 (corundum, most stable polymorph) is a potential origin of a 13 MUm
      feature that appears close to stars. However, no one has directly reproduced the
      13 MUm feature experimentally, and it has remained as a noteworthy unidentified
      infrared band. Here, we report nucleation experiments on Al2O3 nanoparticles
      monitored by a specially designed infrared spectrometer in the microgravity
      environment of a sounding rocket. The conditions approximate to those around
      asymptotic giant branch (AGB) stars. The measured spectra of the nucleated Al2O3
      show a sharp feature at a wavelength of 13.55 MUm and comparable in width to that
      observed near oxygen-rich AGB stars. Our finding that alpha-Al2O3 nucleates under
      certain condition provides a solid basis to elaborate condensation models of dust
      around oxygen-rich evolved stars.

PMID- 30232325
TI  - A role for APP in Wnt signalling links synapse loss with beta-amyloid production.
AB  - In Alzheimer's disease (AD), the canonical Wnt inhibitor Dickkopf-1 (Dkk1) is
      induced by beta-amyloid (Abeta) and shifts the balance from canonical towards non
      canonical Wnt signalling. Canonical (Wnt-beta-catenin) signalling promotes
      synapse stability, while non-canonical (Wnt-PCP) signalling favours synapse
      retraction; thus Abeta-driven synapse loss is mediated by Dkk1. Here we show that
      the Amyloid Precursor Protein (APP) co-activates both arms of Wnt signalling
      through physical interactions with Wnt co-receptors LRP6 and Vangl2, to bi
      directionally modulate synapse stability. Furthermore, activation of non
      canonical Wnt signalling enhances Abeta production, while activation of canonical
      signalling suppresses Abeta production. Together, these findings identify a
      pathogenic-positive feedback loop in which Abeta induces Dkk1 expression, thereby
      activating non-canonical Wnt signalling to promote synapse loss and drive further
      Abeta production. The Swedish familial AD variant of APP (APPSwe) more readily co
      activates non-canonical, at the expense of canonical Wnt activity, indicating
      that its pathogenicity likely involves direct effects on synapses, in addition to
      increased Abeta production. Finally, we report that pharmacological inhibition of
      the Abeta-Dkk1-Abeta positive feedback loop with the drug fasudil can restore the
      balance between Wnt pathways, prevent dendritic spine withdrawal in vitro, and
      reduce Abeta load in vivo in mice with advanced amyloid pathology. These results
      clarify a relationship between Abeta accumulation and synapse loss and provide
      direction for the development of potential disease-modifying treatments.

PMID- 30232329
TI  - Insights into frequent asthma exacerbations from a primary care perspective and
      the implications of UK National Review of Asthma Deaths recommendations.
AB  - The United Kingdom National Review of Asthma Deaths (NRAD) recommends that
      patients who require >=3 courses of oral corticosteroids (OCS) for exacerbations
      in the past year or those on British Thoracic Society (BTS) Step 4/5 treatment
      must be referred to a specialist asthma service. The aim of the study was to
      identify the proportion of asthma patients in primary care that fulfil NRAD
      criteria for specialist referral and factors associated with frequent
      exacerbations. A total of 2639 adult asthma patients from 10 primary care
      practices in Glasgow, UK were retrospectively studied between 2014 and 2015.
      Frequent exacerbators and short-acting beta2-agonist (SABA) over-users were
      identified if they received >=2 confirmed OCS courses for asthma and >=13 SABA
      inhalers in the past year, respectively. Community dispensing data were used to
      assess treatment adherence defined as taking >=75% of prescribed inhaled
      corticosteroid (ICS) dose. The study population included 185 (7%) frequent
      exacerbators, 137 (5%) SABA over-users, and 319 (12%) patients on BTS Step 4/5
      treatment. Among frequent exacerbators, 41% required BTS Step 4/5 treatment, 46%
      had suboptimal ICS adherence, 42% had not attended an asthma review in the past
      year and 42% had no previous input from a specialist asthma service. Older age,
      female gender, BTS Step 4/5, SABA over-use and co-existing COPD diagnosis
      increased the risk of frequent exacerbations independently. Fourteen per 100
      asthma patients would fulfil the NRAD criteria for specialist referral. Better
      collaboration between primary and secondary care asthma services is needed to
      improve chronic asthma care.

PMID- 30232328
TI  - Human Sox4 facilitates the development of CXCL13-producing helper T cells in
      inflammatory environments.
AB  - In human inflammatory sites, PD-1hiCXCR5-CD4+ T cells are involved in the
      formation of ectopic lymphoid-like structures (ELSs) by the secretion of
      chemokine CXCL13, but how the transcription of CXCL13 is regulated in CD4+ T
      cells is still unclear. Here we show that Sox4 is a key transcription factor for
      CXCL13 production in human CD4+ T cells under inflammatory conditions. In vitro
      TGF-beta+, IL-2-neutralizing culture conditions give rise to PD-1hiCXCR5-CD4+ T
      cells that preferentially express CXCL13, and transcriptome analysis and
      lentiviral overexpression indicate Sox4 association with the CXCL13
      transcription. In vivo, Sox4 is significantly upregulated in synovial CD4+ T
      cells, when compared with blood CD4+ T cells, from patients with rheumatoid
      arthritis (RA), and further correlates with ELS formation in RA synovium.
      Overall, our studies suggest that Sox4 contributes to CXCL13 production and ELS
      formation at inflammatory sites in humans.

PMID- 30232327
TI  - Apoepsilon4 disrupts neurovascular regulation and undermines white matter
      integrity and cognitive function.
AB  - The ApoE4 allele is associated with increased risk of small vessel disease, which
      is a cause of vascular cognitive impairment. Here, we report that mice with
      targeted replacement (TR) of the ApoE gene with human ApoE4 have reduced
      neocortical cerebral blood flow compared to ApoE3-TR mice, an effect due to
      reduced vascular density rather than slowing of microvascular red blood cell
      flow. Furthermore, homeostatic mechanisms matching local delivery of blood flow
      to brain activity are impaired in ApoE4-TR mice. In a model of cerebral
      hypoperfusion, these cerebrovascular alterations exacerbate damage to the white
      matter of the corpus callosum and worsen cognitive dysfunction. Using 3-photon
      microscopy we found that the increased white matter damage is linked to an
      enhanced reduction of microvascular flow resulting in local hypoxia. Such
      alterations may be responsible for the increased susceptibility to hypoxic
      ischemic lesions in the subcortical white matter of individuals carrying the
      ApoE4 allele.

PMID- 30232331
TI  - Author Correction: Rab25 augments cancer cell invasiveness through a beta1
      integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin.
AB  - After online publication of this article, the authors noticed an error in the
      Figure 4c and Figure 5c section.

PMID- 30232330
TI  - Asymmetric assembly of high-value alpha-functionalized organic acids using a
      biocatalytic chiral-group-resetting process.
AB  - The preparation of alpha-functionalized organic acids can be greatly simplified
      by adopting a protocol involving the catalytic assembly of achiral building
      blocks. However, the enzymatic assembly of small amino acids and aldehydes to
      form numerous alpha-functionalized organic acids is highly desired and remains a
      significant challenge. Herein, we report an artificially designed chiral-group
      resetting biocatalytic process, which uses simple achiral glycine and aldehydes
      to synthesize stereodefined alpha-functionalized organic acids. This cascade
      biocatalysis comprises a basic module and three different extender modules and
      operates in a modular assembly manner. The engineered Escherichia coli catalysts,
      which contained different module(s), provide access to alpha-keto acids, alpha
      hydroxy acids, and alpha-amino acids with excellent conversion and
      enantioselectivities. Therefore, this biocatalytic process provides an attractive
      strategy for the conversion of low-cost achiral starting materials to high-value
      alpha-functionalized organic acids.

PMID- 30232332
TI  - Rv2346c enhances mycobacterial survival within macrophages by inhibiting TNF
      alpha and IL-6 production via the p38/miRNA/NF-kappaB pathway.
AB  - The intracellular survival of Mycobacterium tuberculosis (Mtb) has a central role
      in the pathogenesis of tuberculosis. Mtb Rv2346c is a member of 6-kDa early
      secreted antigenic target family of proteins, which are known to inhibit the host
      immune responses to promote bacillary persistence in macrophages. However, the
      mechanism through which Rv2346c participates in Mtb pathogenesis is unclear. In
      the present study, recombinant Rv2346c protein was synthesized and used to treat
      Bacillus Calmette-Guerin (BCG)-infected macrophages. The results showed that
      Rv2346c inhibited the proliferation of BCG-infected macrophages and enhanced the
      survival of BCG in macrophages. Tumor necrosis factor-alpha (TNF-alpha) and
      interleukin (IL)-6 were upregulated during BCG infection but downregulated by
      Rv2346c. Additional experiments showed that nuclear transcription factor-kappaB
      (NF-kappaB) in BCG-infected macrophages induced the production of TNF-alpha and
      IL-6. In addition, miR-155 and miR-99b had a suppressive effect on NF-kappaB, and
      the expression of these miRNAs was promoted by p38. Furthermore, Rv2346c was
      shown to decrease the activation of NF-kappaB, whereas it enhanced the
      phosphorylation of p38 and the expression of miR-155 and miR-99b. The function of
      Rv2346c was also verified in Mtb-infected mice. The results showed that Rv2346c
      increased the observed bacterial load and lung injury and downregulated TNF-alpha
      and IL-6 in vivo. Overall, our results reveal that Rv2346c enhances mycobacterial
      survival in macrophages via inhibiting the production of TNF-alpha and IL-6 in a
      p38/miRNA/NF-kappaB pathway-dependent manner, suggesting that Rv2346c acts as a
      crucial virulence factor in Mtb infection and has potential use as a target for
      anti-tuberculosis therapy.

PMID- 30232333
TI  - An alternative pathway of enteric PEDV dissemination from nasal cavity to
      intestinal mucosa in swine.
AB  - Porcine epidemic diarrhea virus (PEDV) has catastrophic impacts on the global pig
      industry. Although the fecal-oral route is generally accepted, an increased
      number of reports indicate that airborne transmission may contribute to PEDV
      outbreak. Here, we show that PEDV could cause typical diarrhea in piglets through
      a nasal spray. Firstly, PEDV can develop a transient nasal epithelium infection.
      Subsequently, PEDV-carrying dendritic cells (DCs) allow the virus to be
      transferred to CD3+ T cells via the virological synapse. Finally, virus-loaded
      CD3+ T cells reach the intestine through the blood circulation, leading to
      intestinal infection via cell-to-cell contact. Our study provides evidence for
      airborne transmission of a gastrointestinal infected coronavirus and illustrates
      the mechanism of its transport from the entry site to the pathogenic site.

PMID- 30232335
TI  - Zigzag carbon as efficient and stable oxygen reduction electrocatalyst for proton
      exchange membrane fuel cells.
AB  - Non-precious-metal or metal-free catalysts with stability are desirable but
      challenging for proton exchange membrane fuel cells. Here we partially unzip a
      multiwall carbon nanotube to synthesize zigzag-edged graphene nanoribbons with a
      carbon nanotube backbone for electrocatalysis of oxygen reduction in proton
      exchange membrane fuel cells. Zigzag carbon exhibits a peak areal power density
      of 0.161 W cm-2 and a peak mass power density of 520 W g-1, superior to most non
      precious-metal electrocatalysts. Notably, the stability of zigzag carbon is
      improved in comparison with a representative iron-nitrogen-carbon catalyst in a
      fuel cell with hydrogen/oxygen gases at 0.5 V. Density functional theory
      calculation coupled with experimentation reveal that a zigzag carbon atom is the
      most active site for oxygen reduction among several types of carbon defects on
      graphene nanoribbons in acid electrolyte. This work demonstrates that zigzag
      carbon is a promising electrocatalyst for low-cost and durable proton exchange
      membrane fuel cells.

PMID- 30232334
TI  - Roquin targets mRNAs in a 3'-UTR-specific manner by different modes of
      regulation.
AB  - The RNA-binding proteins Roquin-1 and Roquin-2 redundantly control gene
      expression and cell-fate decisions. Here, we show that Roquin not only interacts
      with stem-loop structures, but also with a linear sequence element present in
      about half of its targets. Comprehensive analysis of a minimal response element
      of the Nfkbid 3'-UTR shows that six stem-loop structures cooperate to exert
      robust and profound post-transcriptional regulation. Only binding of multiple
      Roquin proteins to several stem-loops exerts full repression, which redundantly
      involved deadenylation and decapping, but also translational inhibition.
      Globally, most Roquin targets are regulated by mRNA decay, whereas a small
      subset, including the Nfat5 mRNA, with more binding sites in their 3'-UTRs, are
      also subject to translational inhibition. These findings provide insights into
      how the robustness and magnitude of Roquin-mediated regulation is encoded in
      complex cis-elements.

PMID- 30232337
TI  - Structural cycle of the Thermus thermophilus PilF ATPase: the powering of type
      IVa pilus assembly.
AB  - Type IV pili are responsible for a diverse range of functions, including
      twitching motility and cell adhesion. Assembly of the pilus fiber is driven by a
      cytoplasmic ATPase: it interacts with an inner membrane complex of biogenesis
      proteins which, in turn, bind to nascent pilin subunits and mediate fiber
      assembly. Here we report the structural characterization of the PilF TFP assembly
      ATPase from Thermus thermophilus. The crystal structure of a recombinant C
      terminal fragment of PilF revealed bound, unhydrolysed ATP, although the full
      length complex was enzymatically active. 3D reconstructions were carried out by
      single particle cryoelectron microscopy for full length apoprotein PilF and in
      complex with AMPPNP. The structure forms an hourglass-like shape, with the ATPase
      domains in one half and the N1 domains in the second half which, we propose,
      interact with the other pilus biogenesis components. Molecular models for both
      forms were generated: binding of AMPPNP causes an upward shift of the N1 domains
      towards the ATPase domains of ~8 A. We advocate a model in which ATP hydrolysis
      is linked to displacement of the N1 domains which is associated with lifting
      pilin subunits out of the inner membrane, and provide the activation energy
      needed to form the pilus fiber.

PMID- 30232336
TI  - Mechano-regulated metal-organic framework nanofilm for ultrasensitive and anti
      jamming strain sensing.
AB  - The development of ultrasensitive, anti-jamming, and durable sensors that can
      precisely distinguish different human body motions are of great importance for
      smart health monitoring and diagnosis. Physical implementation of such flexible
      sensors is still a challenge at the moment. Combining the designs of advanced
      material showing excellent electrochemical properties with the facilitative
      structure engineering, high-performance flexible sensors that satisfy both signal
      detecting and recognition requirements may be made possible. Here we report the
      first metal-organic framework-based strain sensor with accurate signal detection
      and noise-screening properties. Upon doping the tricarboxytriphenyl amine-based
      metal-organic framework nanofilm with iodine, the two-terminal device exhibits
      ultrahigh sensitivity with a gauge factor exceeding 10,000 in the 2.5% to 3.3%
      deformation range for over 5000 dynamic operating cycles and out-of-scale noise
      screening capability. The high-performance strain sensor can easily differentiate
      the moderate muscle hyperspasmia from subtle swaying and vigorous sporting
      activities.

PMID- 30232339
TI  - Arthroscopy Assisted Reduction Percutaneous Internal Fixation versus Open
      Reduction Internal Fixation for Low Energy Tibia Plateau Fractures.
AB  - The purpose of our study was to compare the curative effect of two surgical
      methods for Schatzker type I to III tibia plateau fractures, arthroscopy assisted
      reduction percutaneous internal fixation (ARIF) and open reduction internal
      fixation (ORIF), with the intent of evaluating the quality of evidence to assist
      treatment selection. Searches of PubMed, Cochrane and China National Knowledge
      Infrastructure (CNKI) databases were performed to identify randomized controlled
      trials (RCTs) and quasi-RCTs comparing ARIF and ORIF regarding the following
      outcomes: functional outcomes, perioperative complications and post-traumatic
      osteoarthritis. Odds ratios (OR) and weighted mean differences (MDs) were pooled
      using either a fixed-effects model or random-effects model, depending on the
      heterogeneity of the trials included in the analysis. 19 RCTs and one quasi-RCT
      provided the data from 1272 patients. ARIF was associated with better functional
      outcomes, a lower risk of perioperative complications, and lower risk of post
      traumatic osteoarthritis. After consideration of the quality of evidence of the
      included studies, the advantages provided by ARIF are not substantive over ORIF
      for the treatment of Schatzker type I to III tibia plateau fractures, except
      reducing the risk of perioperative complications.

PMID- 30232338
TI  - Visualising the dynamics of live pancreatic microtumours self-organised through
      cell-in-cell invasion.
AB  - Pancreatic ductal adenocarcinoma (PDAC) reportedly progresses very rapidly
      through the initial carcinogenesis stages including DNA damage and disordered
      cell death. However, such oncogenic mechanisms are largely studied through
      observational diagnostic methods, partly because of a lack of live in vitro
      tumour imaging techniques. Here we demonstrate a simple live-tumour in vitro
      imaging technique using micro-patterned plates (micro/nanoplates) that allows
      dynamic visualisation of PDAC microtumours. When PDAC cells were cultured on a
      micro/nanoplate overnight, the cells self-organised into non-spheroidal
      microtumours that were anchored to the micro/nanoplate through cell-in-cell
      invasion. This self-organisation was only efficiently induced in small-diameter
      rough microislands. Using a time-lapse imaging system, we found that PDAC
      microtumours actively stretched to catch dead cell debris via filo/lamellipoedia
      and suction, suggesting that they have a sophisticated survival strategy
      (analogous to that of starving animals), which implies a context for the
      development of possible therapies for PDACs. The simple tumour imaging system
      visualises a potential of PDAC cells, in which the aggressive tumour dynamics
      reminds us of the need to review traditional PDAC pathogenesis.

PMID- 30232340
TI  - Processive chitinase is Brownian monorail operated by fast catalysis after
      peeling rail from crystalline chitin.
AB  - Processive chitinase is a linear molecular motor which moves on the surface of
      crystalline chitin driven by processive hydrolysis of single chitin chain. Here,
      we analyse the mechanism underlying unidirectional movement of Serratia
      marcescens chitinase A (SmChiA) using high-precision single-molecule imaging, X
      ray crystallography, and all-atom molecular dynamics simulation. SmChiA shows
      fast unidirectional movement of ~50 nm s-1 with 1 nm forward and backward steps,
      consistent with the length of reaction product chitobiose. Analysis of the
      kinetic isotope effect reveals fast substrate-assisted catalysis with time
      constant of ~3 ms. Decrystallization of the single chitin chain from crystal
      surface is the rate-limiting step of movement with time constant of ~17 ms,
      achieved by binding free energy at the product-binding site of SmChiA. Our
      results demonstrate that SmChiA operates as a burnt-bridge Brownian ratchet
      wherein the Brownian motion along the single chitin chain is rectified forward by
      substrate-assisted catalysis.

PMID- 30232341
TI  - Ratio of mitochondrial to nuclear DNA affects contamination estimates in ancient
      DNA analysis.
AB  - In the last decade, ancient DNA research has grown rapidly and started to
      overcome several of its earlier limitations through Next-Generation-Sequencing
      (NGS). Among other advances, NGS allows direct estimation of sample contamination
      from modern DNA sources. First NGS-based approaches of estimating contamination
      measured heterozygosity. These measurements, however, could only be performed on
      haploid genomic regions, i.e. the mitochondrial genome or male X chromosomes, but
      provided no measures of contamination in the nuclear genome of females with their
      two X chromosomes. Instead, female nuclear contamination is routinely
      extrapolated from mitochondrial contamination estimates, but it remains unclear
      if this extrapolation is reliable and to what degree variation in mitochondrial
      to nuclear DNA ratios affects this extrapolation. We therefore analyzed ancient
      DNA from 317 samples of different skeletal elements from multiple sites, spanning
      a temporal range from 7,000 BP to 386 AD. We found that the mitochondrial to
      nuclear DNA (mt/nc) ratio negatively correlates with an increase in endogenous
      DNA content and strongly influenced mitochondrial and nuclear contamination
      estimates in males. The ratio of mt to nc contamination estimates remained stable
      for overall mt/nc ratios below 200, as found particularly often in petrous bones
      but less in other skeletal elements and became more variable above that ratio.

PMID- 30232342
TI  - Mantle Cloaks Based on the Frequency Selective Metasurfaces Designed by Bayesian
      Optimization.
AB  - We propose a full optimization procedure for designing mantle cloaks enclosing
      arbitrary objects, using sub-wavelength conformal frequency selective surface
      (FSS). Rely on the scattering cancellation principle of mantle cloak
      characterized by an average surface reactance, a personal computer can achieve
      this design procedure. By combing a Bayesian optimization (BO) with an
      electromagnetic solver, we can automatically find the optimal parameters of a
      conformal mantle cloak which can nearly cancel the scattering from the enclosed
      objects. It is shown that the results obtained by our method coincide with those
      from a rigorous analytical model and the numerical results by full parametric
      scanning. The proposed methodology opens up a new route for realizing ultra
      wideband illusion scattering of electromagnetic wave, which is important for
      stealth and microwave applications.

PMID- 30232343
TI  - Effects of incorporation of granule-lyophilised platelet-rich fibrin into
      polyvinyl alcohol hydrogel on wound healing.
AB  - Dressings are commonly used to treat skin wounds. In this study, we aimed to
      develop a new scaffold composed of a polyvinyl alcohol (PVA) hydrogel containing
      granule-lyophilised platelet-rich fibrin (G-L-PRF) as a dressing. G-L-PRF was
      prepared by freeze-drying and was then incorporated into PVA hydrogel by freezing
      thawing. Notably, the mechanical strength and degradation rate of the scaffold
      were found to be related to G-L-PRF concentrations, reaching 6.451 * 10-2 MPa and
      17-22%, respectively, at a concentration of 1%. However, the strength decreased
      and the degradation was accelerated when the G-L-PRF concentration was over 1%.
      The elastic properties and biocompatibility of the scaffold were independent of G
      L-PRF concentration, and both showed excellent elasticity and biocompatibility.
      The release of vascular endothelial growth factor and platelet-derived growth
      factor-AB was no significant time dependent. Additionally, application of 1% G-L
      PRF/PVA to acute full-thickness dorsal skin wounds accelerated wound closure at
      days 7 and 9. Healing also increased on day 11. Histological and
      immunohistochemical analyses showed that the scaffold enhanced granulation
      tissue, maturity, collagen deposition, and new vessel formation. These results
      demonstrated that the prepared G-L-PRF/PVA scaffolds accelerated wound healing in
      acute full-thickness skin wounds, suggesting potential applications as an ideal
      wound dressing.

PMID- 30232345
TI  - Elevated Risk of Infections after Spinal Cord Surgery in Relation to Preoperative
      Pressure Ulcers: a Follow-up Study.
AB  - Factors associated with infections after spinal cord surgery were not fully
      understood. This study aimed to evaluate whether preoperative pressure ulcers was
      a risk factor of infections after spinal cord operation. A 1:1 matched follow-up
      study was performed in a tertiary referral center in southwest China between 2010
      and 2015. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated
      using unconditional logistic regression analysis. A total of 334 patients with
      spinal cord surgery were recruited (167 patients with preoperative pressure
      ulcers and 167 patients without preoperative pressure ulcers). Participants
      previously exposed to pressure ulcers had an elevated risk of infections post
      spinal cord operation including surgical site infection (RR: 2.3, 95% CI: 1.1,
      4.7), pneumonia (RR: 2.4, 95% CI: 1.1,5.3), urinary tract infection (RR: 2.8, 95%
      CI: 1.1, 7.3), any kinds of postoperative infections (RR: 3.4, 95% CI: 2.1, 5.6)
      and 30-day postoperative hospitalization for infections (RR: 2.6, 95% CI: 1.1,
      6.0). The associations between preoperative pressure ulcers in stage III to IV
      and postoperative infections were also pronounced, but towards null in stage I to
      II. The study showed an increased risk of infections after spinal cord surgery in
      patients with preoperative pressure ulcers, indicative of an urgent need for
      monitoring postoperative infections and medical treatment for patients with
      pressure sores.

PMID- 30232344
TI  - Identification and characterization of G-quadruplex formation within the EP0
      promoter of pseudorabies virus.
AB  - EP0 is an important early gene that modulates the life cycle of pseudorabies
      virus (PRV). A guanine-rich sequence overlapping with three Sp1 binding sites is
      located upstream of the transcription start site (TSS) in the EP0 promoter. Using
      native polyacrylamide gel electrophoresis (PAGE) and circular dichroism (CD), we
      verified that the G-rich region in the EP0 promoter forms an intramolecular
      parallel G-quadruplex (G4) in the presence of K+ ions. Further dimethyl sulphate
      (DMS) footprinting and Taq polymerase stop assays indicates the potential
      polymorphic folding of G4. In addition, a small chemical ligand, pyridostatin
      (PDS), promotes and stabilizes the formation of G4. Interestingly, based on the
      results of electrophoretic mobility shift assays (EMSA), the Sp1 protein bound to
      G4-bearing DNA with more affinity than DNA lacking the G4 structure. According to
      the luciferase reporter assay, G4 negatively regulates the EP0 promoter activity.
      These results demonstrate that Sp1 and G4 cooperate to regulate EP0 promoter
      activity.

PMID- 30232346
TI  - In silico and in vivo analyses of the mutated human tissue plasminogen activator
      (mtPA) and the antithetical effects of P19 silencing suppressor on its expression
      in two Nicotiana species.
AB  - Human tissue-type plasminogen activator is one of the most important therapeutic
      proteins involved in the breakdown of blood clots following the stroke. A
      mutation was found at position 1541 bp (G514E) and the mutated form was cloned
      into the binary vector pTRAc-ERH. In silico analysis showed that this mutation
      might have no significant effect on the active site of the tissue plasminogen
      activator enzyme. Accordingly, zymography assay confirmed the serine protease
      activity of the mutated form and its derivatives. The expression of the mutated
      form was verified with/without co-agroinjection of the P19 gene silencing
      suppressor in both Nicotiana tabacum and N. benthamiana. The ELISA results showed
      that the concentration of the mutated form in the absence of P19 was 0.65% and
      0.74% of total soluble protein versus 0.141% and 1.36% in the presence of P19 in
      N. benthamiana and N. tabacum, respectively. In N. tabacum, co-agroinjection of
      P19 had the synergistic effect and increased the mutated tissue plasminogen
      activator production two-fold higher. However, in N. benthamiana, the presence of
      P19 had the adverse effect of five-fold reduction in the concentration. Moreover,
      results showed that the activity of the mutated form and its derivatives was more
      than that of the purified commercial tissue plasminogen activator.

PMID- 30232347
TI  - Molecular hydrogen protects against ischemia-reperfusion injury in a mouse fatty
      liver model via regulating HO-1 and Sirt1 expression.
AB  - Fatty liver has lower tolerance against ischemia-reperfusion (I/R) injury in
      liver operations, including liver transplantation. Seeking to ameliorate liver
      injury following I/R in fatty liver, we examined the protective effect of
      hydrogen (H2) saline on I/R liver injury in a methionine and choline-deficient
      plus high fat (MCDHF) diet-induced fatty liver mouse model. Saline containing 7
      ppm H2 was administrated during the process of I/R. Livers were obtained and
      analyzed. Primary hepatocytes and Kupffer cells (KCs) were obtained from fatty
      liver and subjected to hypoxia/reoxygenation. Apoptosis-related proteins and
      components of the signaling pathway were analyzed after treatment with hydrogen
      gas. The MCDHF I/R group showed higher levels of AST and ALT in serum, TUNEL
      positive apoptotic cells, F4/80 immunopositive cells, mRNA levels of inflammatory
      cytokines, constituents of the signaling pathway, pro-apoptotic molecules in
      liver, and KCs and/or primary hepatocytes, compared to the control group. In
      contrast, H2 treatment significantly suppressed the signs of I/R injury in fatty
      liver. Moreover, the expression of Bcl-2, HO-1, and Sirt1 in liver, KCs, and
      hepatocytes by hydrogen gas were increased, whereas caspase activation, Bax, and
      acetylation of p53 were suppressed by hydrogen gas. These results demonstrated
      that H2 treatment ameliorated I/R liver injury in a fatty liver model by reducing
      hepatocyte apoptosis, inhibiting macrophage activation and inflammatory
      cytokines, and inducing HO-1 and Sirt1 expression. Taken togather, treatment with
      H2 saline may have a protective effect and safe therapeutic activity during I/R
      events, such as in liver transplantation with fatty liver.

PMID- 30232348
TI  - Bacterial cell wall nanoimaging by autoblinking microscopy.
AB  - Spurious blinking fluorescent spots are often seen in bacteria during single
      molecule localization microscopy experiments. Although this 'autoblinking'
      phenomenon is widespread, its origin remains unclear. In Deinococcus strains, we
      observed particularly strong autoblinking at the periphery of the bacteria,
      facilitating its comprehensive characterization. A systematic evaluation of the
      contributions of different components of the sample environment to autoblinking
      levels and the in-depth analysis of the photophysical properties of autoblinking
      molecules indicate that the phenomenon results from transient binding of
      fluorophores originating mostly from the growth medium to the bacterial cell
      wall, which produces single-molecule fluorescence through a Point Accumulation
      for Imaging in Nanoscale Topography (PAINT) mechanism. Our data suggest that the
      autoblinking molecules preferentially bind to the plasma membrane of bacterial
      cells. Autoblinking microscopy was used to acquire nanoscale images of live,
      unlabeled D. radiodurans and could be combined with PALM imaging of PAmCherry
      labeled bacteria in two-color experiments. Autoblinking-based super-resolved
      images provided insight into the formation of septa in dividing bacteria and
      revealed heterogeneities in the distribution and dynamics of autoblinking
      molecules within the cell wall.

PMID- 30232349
TI  - N-Phenylquinazolin-2-amine Yhhu4952 as a novel promotor for oligodendrocyte
      differentiation and myelination.
AB  - Oligodendrocytes are a type of glial cells that ensheath multiple neuronal axons
      and form myelin. Under pathological conditions, such as multiple sclerosis (MS),
      inflammatory damage to myelin and oligodendrocytes leads to demyelination.
      Although the demyelinated regions can partially resolve functional deficits
      through remyelination, however, as the disease progresses, remyelination
      typically becomes incomplete and ultimately fails. One possible explanation for
      this failure is the activation of the Notch pathway in MS lesions, which impedes
      oligodendrocyte precursor cells (OPCs) at maturation. This leads to a potential
      target for remyelination. Here, we have identified a compound Yhhu4952 that
      promoted the maturation of cultured OPCs in a dose-dependent and time-dependent
      manner. Neonatal rats showed a significant increase in the expression of myelin
      basic protein (MBP) and the prevalence of mature oligodendrocytes in the corpus
      callosum after Yhhu4952 treatment. The compound was also effective in promoting
      remyelination in cuprizone-induced demyelination model and improving severity
      scores in experimental autoimmune encephalomyelitis (EAE) model. Mechanism
      studies revealed that Yhhu4952 promotes OPC differentiation through the
      inhibition of the Jagged1-Notch1 pathway. These findings suggest Yhhu4952 is
      potentially useful for proceeding oligodendrocyte differentiation and
      remyelination.

PMID- 30232350
TI  - Pretreatment Identification of Head and Neck Cancer Nodal Metastasis and
      Extranodal Extension Using Deep Learning Neural Networks.
AB  - Identification of nodal metastasis and tumor extranodal extension (ENE) is
      crucial for head and neck cancer management, but currently only can be diagnosed
      via postoperative pathology. Pretreatment, radiographic identification of ENE, in
      particular, has proven extremely difficult for clinicians, but would be greatly
      influential in guiding patient management. Here, we show that a deep learning
      convolutional neural network can be trained to identify nodal metastasis and ENE
      with excellent performance that surpasses what human clinicians have historically
      achieved. We trained a 3-dimensional convolutional neural network using a dataset
      of 2,875 CT-segmented lymph node samples with correlating pathology labels, cross
      validated and fine-tuned on 124 samples, and conducted testing on a blinded test
      set of 131 samples. On the blinded test set, the model predicted ENE and nodal
      metastasis each with area under the receiver operating characteristic curve (AUC)
      of 0.91 (95%CI: 0.85-0.97). The model has the potential for use as a clinical
      decision-making tool to help guide head and neck cancer patient management.

PMID- 30232351
TI  - Multi-unit relations among neural, self-report, and behavioral correlates of
      emotion regulation in comorbid depression and obesity.
AB  - Depression is a leading cause of disability and is commonly comorbid with
      obesity. Emotion regulation is impaired in both depression and obesity. In this
      study, we aimed to explicate multi-unit relations among brain connectivity,
      behavior, and self-reported trait measures related to emotion regulation in a
      comorbid depressed and obese sample (N = 77). Brain connectivity was quantified
      as fractional anisotropy (FA) of the uncinate fasciculi, a white matter tract
      implicated in emotion regulation and in depression. Use of emotion regulation
      strategies was assessed using the Emotion Regulation Questionnaire (ERQ). We
      additionally measured reaction times to identifying negative emotions, a
      behavioral index of depression-related emotion processing biases. We found that
      greater right uncinate fasciculus FA was related to greater usage of suppression
      (r = 0.27, p = 0.022), and to faster reaction times to identifying negative
      emotions, particularly sadness (r = -0.30, p = 0.010) and fear (r = -0.35, p =
      0.003). These findings suggest that FA of the right uncinate fasciculus
      corresponds to maladaptive emotion regulation strategies and emotion processing
      biases that are relevant to co-occurring depression and obesity. Interventions
      that consider these multi-unit associations may prove to be useful for subtyping
      and improving clinical outcomes for comorbid depression and obesity.

PMID- 30232352
TI  - Effect of Electromagnetic Stimulation of Amaranth Seeds of Different Initial
      Moisture on the Germination Parameters and Photosynthetic Pigments Content.
AB  - The influence of stimulation with He-Ne laser light, alternating magnetic field
      and the combination of these factors on germination parameters of amaranth seeds
      and on the chlorophyll and carotenoid content in seedlings was investigated.
      During the stimulation the amaranth seeds had a different initial moisture
      content. From the germination characteristics of the seeds as the function of
      humidity, three maxima and one minimum value of the germination parameters (the
      relative germination capacity NK REL, the relative maximum germination rate SK
      MAX REL and the maximum germination index WK MAX) were obtained. In the majority
      of cases, the extremities coincided with the changes in the chlorophyll and
      carotenoid content in the seedlings. The presented research is innovative in the
      field of seed biology since no similar studies have been conducted before. It is
      difficult to interpret the results referring to the literature on this subject.
      The results can be explained as follows: the observed effect must be related to
      the stages of the water uptake by the seeds. The three stages of the water uptake
      associated with the seed germination process coincide with the maximum values in
      the germination parameters and with the change in the photosynthetic pigment
      content in seedlings.

PMID- 30232353
TI  - A case of behavioural diversification in male floral function - the evolution of
      thigmonastic pollen presentation.
AB  - Obvious movements of plant organs have fascinated scientists for a long time.
      They have been studied extensively, but few behavioural studies to date have
      dealt with them, and hardly anything is known about their evolution. Here, we
      present a large experimental dataset on the stamen movement patterns found in the
      Loasaceae subfam. Loasoideae (Cornales). An evolutionary transition from
      autonomous-only to a combination of autonomous and thigmonastic stamen movement
      with increased complexity was experimentally demonstrated. We compare the stamen
      movement patterns with extensive pollinator observations and discuss it in the
      context of male mating behavior. Thigmonastic pollen presentation via stamen
      movements appears to be a crucial component of floral adaptation to pollinator
      behaviour, evolving in concert with complex adjustments of flower signal, reward
      and morphology. We hypothesize that rapid adjustments of pollen presentation
      timing may play a significant role in the diversification of this plant group,
      representing a striking example for the evolutionary significance of plant
      behaviour.

PMID- 30232354
TI  - Altitudinal dependence of PCBs and PBDEs in soil along the two sides of Mt.
      Sygera, southeastern Tibetan Plateau.
AB  - Surface soil samples were collected from Mt. Sygera in the southeast of Tibetan
      Plateau to investigate the altitudinal distribution of PCBs and PBDEs along the
      two sides of the mountain. The average concentrations of PCBs and PBDEs were 177
      pg g-1 dw and 15 pg g-1 dw, respectively. The relationships between the log
      transformed TOC-normalized concentrations and the altitudes showed different
      trends on the two sides. On the windward side, there was a positive correlation
      for the heavier PCBs; while on the leeward side, the concentrations increased and
      then decreased for PCBs and PBDEs at the altitude of 4100-4200 m, corresponding
      to the change in vegetation. The observed discrepancy on the two sides of the
      mountain demonstrated different key factors associated with precipitation and the
      forest canopy. Additionally, values of windward-leeward Enrichment Factors (W/L
      EFs) for the heavier PCB congeners (PCB-138, 153, and -180) were an order of
      magnitude higher in sites above 4200 m, which also suggested that vegetation
      played an important role in the altitudinal accumulation of POPs in soil. This is
      one of the very few studies that have revealed the differences in altitudinal
      accumulation of POPs along the two sides of a mountain.

PMID- 30232355
TI  - Better than DEET Repellent Compounds Derived from Coconut Oil.
AB  - Hematophagous arthropods are capable of transmitting human and animal pathogens
      worldwide. Vector-borne diseases account for 17% of all infectious diseases
      resulting in 700,000 human deaths annually. Repellents are a primary tool for
      reducing the impact of biting arthropods on humans and animals. N,N-Diethyl-meta
      toluamide (DEET), the most effective and long-lasting repellent currently
      available commercially, has long been considered the gold standard in insect
      repellents, but with reported human health issues, particularly for infants and
      pregnant women. In the present study, we report fatty acids derived from coconut
      oil which are novel, inexpensive and highly efficacious repellant compounds.
      These coconut fatty acids are active against a broad array of blood-sucking
      arthropods including biting flies, ticks, bed bugs and mosquitoes. The medium
      chain length fatty acids from C8:0 to C12:0 were found to exhibit the predominant
      repellent activity. In laboratory bioassays, these fatty acids repelled biting
      flies and bed bugs for two weeks after application, and ticks for one week.
      Repellency was stronger and with longer residual activity than that of DEET. In
      addition, repellency was also found against mosquitoes. An aqueous starch-based
      formulation containing natural coconut fatty acids was also prepared and shown to
      protect pastured cattle from biting flies up to 96-hours in the hot summer,
      which, to our knowledge, is the longest protection provided by a natural
      repellent product studied to date.

PMID- 30232357
TI  - Maternally inherited 133kb deletion of 14q32 causing Kagami-Ogata syndrome.
AB  - We present a case of a newborn female with multiple anomalies demonstrating that
      the causes of imprinting disorders rely not only on the parent-of-origin of the
      chromosomal aberrations, but also the scope of genes contained in the imprinted
      region. The newborn female presented with prenatal polyhydramnios, neonatal
      respiratory distress, distal contractures, abdominal hernia, bell-shaped thorax,
      and abnormal ribs. The neonate required mechanical ventilation due to apnea,
      underwent surgery for laryngomalacia, and showed development delay by age 11
      months. Chromosomal microarray analysis identified a single copy number loss in
      chromosome region 14q32.2q32.31, containing genes that are differentially
      expressed based on parent-of-origin. Microarray analysis also confirmed the
      identical deletion in the patient's mother, who was reported to be normal.
      Additional molecular analyses determined the exact size and breakpoints of the
      deletion as well as methylation states in both the patient and her mother. The
      maternally transmitted deletion was responsible for Kagami-Ogata syndrome in the
      patient.

PMID- 30232356
TI  - Overexpression of an auxin receptor OsAFB6 significantly enhanced grain yield by
      increasing cytokinin and decreasing auxin concentrations in rice panicle.
AB  - Auxin plays critical roles in many developmental processes of plants. The auxin
      signaling pathway is a series of plant responses to auxin stimuli. However, the
      functions of many genes in this pathway are still obscure. As auxin receptors,
      TIR/AFB family genes encode F-Box proteins that directly bind auxin and then
      transduce the stimulus through the signaling pathway. In this paper, we generated
      an overexpression line of Auxin-signaling F-Box 6 (OsAFB6) in rice, which largely
      delayed heading, greatly increased spikelets per panicle and primary branch
      number and ultimately enhanced grain yield by 50%. OsAFB6 is preferentially
      expressed in young tissues with stronger meristem activities and suppresses
      flowering by upregulating OsRR1 and downregulating Ehd1 expression levels.
      Overexpression of OsAFB6 delayed heading, increased cytokinin (CK) by suppressing
      the expression level of Gn1a and simultaneously decreased the IAA concentration
      in the young panicle, which promoted inflorescence meristem development and
      resulted in large panicles with more spikelets per panicle, primary branches and
      increased grain yield. It would be a beneficial strategy to generate lines with
      varied expression levels of OsAFB6 to breed high-yielding cultivars for specific
      regions that can fully utilize the local sunlight and temperature resources.

PMID- 30232358
TI  - Green microalgae in marine coastal waters: The Ocean Sampling Day (OSD) dataset.
AB  - The ecology and distribution of green phytoplankton (Chlorophyta) in the ocean is
      poorly known because most studies have focused on groups with large cell size
      such as diatoms or dinoflagellates that are easily recognized by traditional
      techniques such as microscopy. The Ocean Sampling Day (OSD) project sampled
      surface waters quasi-simultaneously at 141 marine locations, mostly in coastal
      waters. The analysis of the 18S V4 region OSD metabarcoding dataset reveals that
      Chlorophyta are ubiquitous and can be locally dominant in coastal waters.
      Chlorophyta represented 29% of the global photosynthetic reads (Dinoflagellates
      excluded) and their contribution was especially high at oligotrophic stations (up
      to 94%) and along the European Atlantic coast. Mamiellophyceae dominated most
      coastal stations. At some coastal stations, they were replaced by
      Chlorodendrophyceae, Ulvophyceae, Trebouxiophyceae or Chlorophyceae as the
      dominating group, while oligotrophic stations were dominated either by
      Chloropicophyceae or the uncultured prasinophytes clade IX. Several Chlorophyta
      classes showed preferences in terms of nitrate concentration, distance to the
      coast, temperature and salinity. For example, Chlorophyceae preferred cold and
      low salinity coastal waters, and prasinophytes clade IX warm, high salinity,
      oligotrophic oceanic waters.

PMID- 30232359
TI  - Association between Subcortical Morphology and Cerebral White Matter Energy
      Metabolism in Neonates with Congenital Heart Disease.
AB  - Complex congenital heart disease (CHD) is associated with neurodevelopmental
      impairment, the mechanism of which is unknown. Cerebral cortical dysmaturation in
      CHD is linked to white matter abnormalities, including developmental
      vulnerability of the subplate, in relation to oxygen delivery and metabolism
      deficits. In this study, we report associations between subcortical morphology
      and white matter metabolism in neonates with CHD using quantitative magnetic
      resonance imaging (MRI) and spectroscopy (MRS). Multi-modal brain imaging was
      performed in three groups of neonates close to term-equivalent age: (1) term CHD
      (n = 56); (2) preterm CHD (n = 37) and (3) preterm control group (n = 22).
      Thalamic volume and cerebellar transverse diameter were obtained in relation to
      cerebral metrics and white matter metabolism. Short echo single-voxel MRS of
      parietal and frontal white matter was used to quantitate metabolites related to
      brain maturation (n-acetyl aspartate [NAA], choline, myo-inositol),
      neurotransmitter (glutamate), and energy metabolism (glutamine, citrate, creatine
      and lactate). Multi-variate regression was performed to delineate associations
      between subcortical morphological measurements and white matter metabolism
      controlling for age and white matter injury. Reduced thalamic volume, most
      pronounced in the preterm control group, was associated with increased citrate
      levels in all three group in the parietal white matter. In contrast, reduced
      cerebellar volume, most pronounced in the preterm CHD group, was associated with
      reduced glutamine in parietal grey matter in both CHD groups. Single ventricle
      anatomy, aortic arch obstruction, and cyanotic lesion were predictive of the
      relationship between reduced subcortical morphometry and reduced GLX
      (particularly glutamine) in both CHD cohorts (frontal white matter and parietal
      grey matter). Subcortical morphological associations with brain metabolism were
      also distinct within each of the three groups, suggesting these relationships in
      the CHD groups were not directly related to prematurity or white matter injury
      alone. Taken together, these findings suggest that subplate vulnerability in CHD
      is likely relevant to understanding the mechanism of both cortical and
      subcortical dysmaturation in CHD infants. Future work is needed to link this
      potential pattern of encephalopathy of CHD (including the constellation of grey
      matter, white matter and brain metabolism deficits) to not only abnormal fetal
      substrate delivery and oxygen conformance, but also regional deficits in cerebral
      energy metabolism.

PMID- 30232360
TI  - Mutagen-induced phytotoxicity in maize seed germination is dependent on ROS
      scavenging capacity.
AB  - Ethidium bromide (EB) and acridine orange (AO) bind to nucleic acids and are thus
      considered as potential mutagens. In this study, the effects of EB and AO on the
      germination behaviours of white, yellow, red, and purple maize seeds were
      investigated. The results indicate that low concentrations of EB (50 MUg mL-1)
      and AO (500 MUg mL-1) promote germination, particularly for the white and yellow
      seeds. However, high concentrations of EB (0.5 mg mL-1) and AO (5 mg mL-1)
      significantly inhibit germination, with the level of inhibition decreasing in the
      following order: white > yellow > red > purple. In addition, EB and AO induce
      H2O2 production in a concentration-dependent manner. The effects of these
      mutagens on seed germination were partly reversed by dimethyl thiourea, a
      scavenger of reactive oxygen species (ROS), and diphenylene iodonium (DPI), an
      inhibitor of NADPH oxidase, while the effects were enhanced by treatment with
      H2O2 and 3-amino-1,2,4-triazole, a specific inhibitor of catalase. In addition,
      AO and EB profoundly increased NADPH oxidase activities in germinating seeds. The
      treatment of seeds with EB and AO did not affect the growth or drought tolerance
      of the resultant seedlings. The findings suggest that the mechanism of mutagen
      toxicity is related to the induction of ROS production.

PMID- 30232361
TI  - Overexpression of Different Types of Microbial Rhodopsins with a Highly
      Expressible Bacteriorhodopsin from Haloarcula marismortui as a Single Protein in
      E. coli.
AB  - Microbial rhodopsins (M-Rho) are found in Archaea, Bacteria and some species of
      Eukarya and serve as light-driven ion pumps or mediate phototaxis responses in
      various biological systems. We previously reported an expression system using a
      highly expressible mutant, D94N-HmBRI (HEBR) from Haloarcula marismortui, as a
      leading tag to assist in the expression of membrane proteins that were otherwise
      difficult to express in E. coli. In this study, we show a universal strategy for
      the expression of two M-Rho proteins, either the same or different types, as one
      fusion protein with the HEBR system. One extra transmembrane domain was
      engineered to the C-terminal of HEBR to express another target M-Rho. The average
      expression yield in this new system reached a minimum of 2 mg/L culture, and the
      maximum absorbance of the target M-Rho remained unaltered in the fusion forms.
      The fusion protein showed a combined absorbance spectrum of a lone HEBR and
      target M-Rho. The function of the target M-Rho was not affected after examination
      with functional tests, including the photocycle and proton pumping activity of
      fusion proteins. In addition, an otherwise unstable sensory rhodopsin, HmSRM,
      showed the same or even improved stability under various temperatures, salt
      concentrations, and a wide range of pH conditions. This HEBR platform provides
      the possibility to construct multi-functional, stoichiometric and color-tuning
      fusion proteins using M-Rho from haloarchaea.

PMID- 30232362
TI  - Laser surface structuring of diamond with ultrashort Bessel beams.
AB  - We investigate the effect of ultrafast laser surface machining on a
      monocrystalline synthetic diamond sample by means of pulsed Bessel beams. We
      discuss the differences of the trench-like microstructures generated in various
      experimental conditions, by varying the beam cone angle, the energy and pulse
      duration, and we present a brief comparison of the results with those obtained
      with the same technique on a sapphire sample. In diamond, we obtain V-shaped
      trenches whose surface width varies with the cone angle, and which are featured
      by micrometer sized channels having depths in the range of 10-20 MUm. By laser
      writing crossed trenches we are also able to create and tailor on the diamond
      surface pillar-like or tip-like microstructures potentially interesting for large
      surface functionalization, cells capturing and biosensing.

PMID- 30232363
TI  - Long-term evolution on complex fitness landscapes when mutation is weak.
AB  - Understanding evolution on complex fitness landscapes is difficult both because
      of the large dimensionality of sequence space and the stochasticity inherent to
      population-genetic processes. Here, I present an integrated suite of mathematical
      tools for understanding evolution on time-invariant fitness landscapes when
      mutations occur sufficiently rarely that the population is typically monomorphic
      and evolution can be modeled as a sequence of well-separated fixation events. The
      basic intuition behind this suite of tools is that surrounding any particular
      genotype lies a region of the fitness landscape that is easy to evolve to, while
      other pieces of the fitness landscape are difficult to evolve to (due to
      distance, being across a fitness valley, etc.). I propose a rigorous definition
      for this "dynamical neighborhood" of a genotype which captures several aspects of
      the distribution of waiting times to evolve from one genotype to another. The
      neighborhood structure of the landscape as a whole can be summarized as a matrix,
      and I show how this matrix can be used to approximate the expected waiting time
      for certain evolutionary events to occur and to provide an intuitive
      interpretation to existing formal results on the index of dispersion of the
      molecular clock.

PMID- 30232364
TI  - Time course of focused ultrasound effects on beta-amyloid plaque pathology in the
      TgCRND8 mouse model of Alzheimer's disease.
AB  - Previous studies have demonstrated that temporarily increasing the permeability
      of the blood-brain barrier using focused ultrasound can reduce beta-amyloid
      plaque load and improve cognitive function in animal models of Alzheimer's
      disease. However, the underlying mechanism and duration for which the effects of
      one treatment persists for are unknown. Here, we used in vivo two-photon
      fluorescence microscopy to track changes in beta-amyloid plaque sizes in the
      TgCRND8 mouse model of Alzheimer's disease after one focused ultrasound
      treatment. We found that one treatment reduced plaques to 62 +/- 16% (p <= 0.001)
      of their original volume two days post-sonication; this decrease in size
      persisted for two weeks. We then sought to evaluate the effectiveness of biweekly
      focused ultrasound treatments using magnetic resonance imaging-guided focused
      ultrasound treatments. Three to five biweekly treatments resulted in a 27 +/- 7%
      (p <= 0.01) decrease in plaque number and 40 +/- 10% (p <= 0.01) decrease in
      plaque surface area compared to untreated littermates. This study demonstrates
      that one focused ultrasound treatment reduces the size of existing beta-amyloid
      plaques for two weeks, and that repeated biweekly focused ultrasound treatments
      is an effective method of reducing beta-amyloid pathology in moderate-to-late
      stages of Alzheimer's disease.

PMID- 30232365
TI  - Sensitive and rapid quantification of exosomes by fusing luciferase to exosome
      marker proteins.
AB  - Exosomes have emerged as important mediators of intercellular communication.
      Although their modes of action have been elucidated, the molecular mechanisms
      underlying their secretion, sorting of molecules, uptake into recipient cells,
      and biological distribution in vivo remain elusive. Here, we present a novel
      system for quantifying secreted exosomes by introducing ectopic or CRISPR/Cas9
      mediated knock-in of luciferase-fusion exosome markers such as CD63. This
      luciferase-based method makes it possible to measure exosomes secreted into the
      culture medium with high linearity and wide dynamic range in a high-throughput
      manner. We demonstrate that data obtained by luminescent quantification are well
      correlated with data obtained by conventional nanoparticle tracking analysis
      under multiple conditions. In addition, our system is capable of evaluating the
      recipient cells or tissues that take up exosomes, as well as visualizing exosomes
      in vivo. The proposed system represents a powerful tool for understanding the
      molecular mechanisms underlying exosome production, uptake, and long-term
      distribution.

PMID- 30232366
TI  - Dietary niches of terrestrial cercopithecines from the Plio-Pleistocene Shungura
      Formation, Ethiopia: evidence from Dental Microwear Texture Analysis.
AB  - This study aims to explore the feeding ecology of two terrestrial papionins,
      Papio and Theropithecus from the Shungura Formation in Ethiopia, the most
      complete stratigraphic and paleontological record of the African Plio
      Pleistocene. Two aspects were evaluated using Dental Microwear Texture Analysis:
      differences in diet between the extinct genera and their extant relatives, and
      any potential dietary fluctuations over time. Amongst more than 2,500
      cercopithecid dental remains, 154 Theropithecus molars and 60 Papio molars were
      considered. Thirty-nine extant wild baboons and 20 wild geladas were also
      considered. The results show that diets of extinct monkeys from Member G already
      differed between genera as it is the case for their extant representatives. The
      shearing facets on the Theropithecus molars display significant variations in
      microwear textures, suggesting several dietary shifts over time. Two events point
      to higher intakes of herbaceous monocots (tougher than dicots foliages), at about
      2.91 Ma (between members B and C) and at 2.32 Ma (between members E and F). These
      two events are separated by an inverse trend at about 2.53 Ma (between members C
      and D). Some of these variations, such as between members E and F are supported
      by the enamel carbon isotopic composition of herbivorous mammals and with
      paleovegetation evidence.

PMID- 30232367
TI  - A transgenic zebrafish model for in vivo long-term imaging of retinotectal
      synaptogenesis.
AB  - The retinotectal synapse in larval zebrafish, combined with live time-lapse
      imaging, provides an advantageous model for study of the development and
      remodelling of central synapses in vivo. In previous studies, these synapses were
      labelled by transient expression of fluorescence-tagged synaptic proteins, which
      resulted in the dramatic variation of labelling patterns in each larva. Here,
      using GAL4-Upstream Activating Sequence (GAL4-UAS) methodology, we generated
      stable transgenic lines, which express EGFP-tagged synaptophysin (a presynaptic
      protein) in retinal ganglion cells (RGCs), to reliably label the pre-synaptic
      site of retinotectal synapses. This tool avoids the variable labelling of RGCs
      that occurs in transient transgenic larvae. We obtained several stable transgenic
      lines that differ consistently in the number of labelled RGCs. Using stable lines
      that consistently had a single labelled RGC, we could trace synaptogenic dynamics
      on an individual RGC axonal arbor across different developmental stages. In the
      stable lines that consistently had multiple labelled RGCs, we could
      simultaneously monitor both pre- and post-synaptic compartments by combining
      transient labelling of post-synaptic sites on individual tectal neurons. These
      tools allowed us to investigate molecular events underlying synaptogenesis and
      found that the microRNA-132 (miR-132) is required for developmental
      synaptogenesis. Thus, these transgenic zebrafish stable lines provide appropriate
      tools for studying central synaptogenesis and underlying molecular mechanisms in
      intact vertebrate brain.

PMID- 30232369
TI  - Computational tools to unmask transposable elements.
AB  - A substantial proportion of the genome of many species is derived from
      transposable elements (TEs). Moreover, through various self-copying mechanisms,
      TEs continue to proliferate in the genomes of most species. TEs have contributed
      numerous regulatory, transcript and protein innovations and have also been linked
      to disease. However, notwithstanding their demonstrated impact, many genomic
      studies still exclude them because their repetitive nature results in various
      analytical complexities. Fortunately, a growing array of methods and software
      tools are being developed to cater for them. This Review presents a summary of
      computational resources for TEs and highlights some of the challenges and
      remaining gaps to perform comprehensive genomic analyses that do not simply
      'mask' repeats.

PMID- 30232368
TI  - Genetic analysis of ATP13A2, PLA2G6 and FBXO7 in a cohort of Chinese patients
      with early-onset Parkinson's disease.
AB  - Several genes have already been certified as causative genes in patients with
      autosomal recessive early-onset Parkinson's syndrome with pyramidal tract signs,
      including ATP13A2, PLA2G6 and FBXO7. Variants in these three genes may also play
      roles in early-onset Parkinson's disease (EOPD). In order to investigate the
      contribution of genetic variants in these three genes to Chinese sporadic EOPD
      patients, we screened 101 Chinese sporadic EOPD patients and 83 age- and sex
      matched healthy controls using direct sequencing. Interpretation of those
      detected variants was performed based on the guidelines developed by the American
      College of Medical Genetics and Genomics (ACMG). Two missense variants, p.G360E
      and p.T733M, with "uncertain significance" classification were identified in the
      ATP13A2 gene and five synonymous variants were significantly over-represented in
      EOPD patients. Two missense variants, p.R53C and p.T319M, were absent in both our
      control group and online databases, classified as "likely pathogenic" in the
      PLA2G6 gene. Only benign variants were identified in the FBXO7 gene. These
      results indicate that rare variants of PLA2G6 may contribute to PD susceptibility
      in Chinese population, the ATP13A2 might be associated with higher risk for
      sporadic EOPD, while the FBXO7 gene doesn't seem to be a risk factor to develop
      sporadic PD in Chinese population. Further biochemical and molecular biological
      studies needs to be conducted to support our main results in our future
      researches.

PMID- 30232370
TI  - Ag+ doped into azo-linked conjugated microporous polymer for volatile iodine
      capture and detection of heavy metal ions.
AB  - We herein report the construction of a novel azo-linked conjugated microporous
      polymers (Ag@AzoTPE-CMP), which possesses permanent porous structure and Ag+
      loading up of 7.62% in the skeleton as effective sorption sites. Ag@AzoTPE-CMP
      shows considerable adsorption capacity of iodine of 202 wt% in iodine vapor at
      350 K. In addition, Ag@AzoTPE-CMP can effectively remove heavy ions from ethanol
      water solution.

PMID- 30232371
TI  - The language profile of formal thought disorder.
AB  - Formal thought disorder (FTD) is clinically manifested as disorganized speech,
      but there have been only few investigations of its linguistic properties. We
      examined how disturbance of thought may relate to the referential function of
      language as expressed in the use of noun phrases (NPs) and the complexity of
      sentence structures. We used a comic strip description task to elicit language
      samples from 30 participants with schizophrenia (SZ), 15 with moderate or severe
      FTD (SZ + FTD), and 15 minimal or no FTD (SZ-FTD), as well as 15 first-degree
      relatives of people with SZ (FDRs) and 15 neurotypical controls (NC). We
      predicted that anomalies in the normal referential use of NPs, sub-divided into
      definite and indefinite NPs, would identify FTD; and also that FTD would also be
      linked to reduced linguistic complexity as specifically measured by the number of
      embedded clauses and of grammatical dependents. Participants with SZ + FTD
      produced more referential anomalies than NC and produced the fewest definite NPs,
      while FDRs produced the most and thus also differed from NC. When referential
      anomalies were classed according to the NP type in which they occurred, the SZ +
      FTD group produced more anomalies in definite NPs than NC. Syntactic errors did
      not distinguish groups, but the SZ + FTD group exhibited significantly less
      syntactic complexity than non-SZ groups. Exploratory regression analyses
      suggested that production of definite NPs distinguished the two SZ groups. These
      results demonstrate that FTD can be identified in specific grammatical patterns
      which provide new targets for detection, intervention, and neurobiological
      studies.

PMID- 30232372
TI  - Genetic variant in IL-32 is associated with the ex vivo cytokine production of
      anti-TNF treated PBMCs from rheumatoid arthritis patients.
AB  - About 60% of RA patients don't achieve good response with biological disease
      modifying anti-rheumatic drugs bDMARD treatment (including TNF inhibitors,
      TNFi's). Previously, a link between TNFalpha and interleukin (IL)-32 was reported
      in RA. However, the exact mechanism linking IL-32 to response to treatment as not
      been studied yet. Therefore, we explored the influence of a promoter single
      nucleotide polymorphism (SNP) rs4786370 in IL-32 on clinical responsiveness to
      TNFi's in RA patients, potentially serving as new biomarker in RA. Expression of
      pro-inflammatory cytokines by peripheral mononuclear cells (PBMCs) from RA
      patients and healthy individuals were studied. Moreover, "ex vivo response" and
      clinical response to anti-TNFalpha therapy (etanercept, adalimumab) were measured
      and stratified for the IL-32 SNP. Higher IL-32 protein production was observed in
      RA patients. Additionally, patients bearing the CC genotype showed higher IL-32
      protein and cytokine expression. DAS28 was independent of the promoter SNP,
      however, the "ex vivo" cytokine response was not. IL-32 mRNA and protein
      production was higher in RA patients, with a trend towards higher concentrations
      in patients bearing the CC genotype. Furthermore, genotype dependent IL-1 beta
      production might predict clinical response to etanercept/adalimumab. This
      indicates that IL-32 could play a role in predicting response to treatment in RA.

PMID- 30232373
TI  - Pseudomonas aeruginosa ExoS Induces Intrinsic Apoptosis in Target Host Cells in a
      Manner That is Dependent on its GAP Domain Activity.
AB  - Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes
      serious infections in immunocompromised individuals and cystic fibrosis patients.
      ExoS and ExoT are two homologous bifunctional Type III Secretion System (T3SS)
      virulence factors that induce apoptosis in target host cells. They possess a
      GTPase Activating Protein (GAP) domain at their N-termini, which share ~76%
      homology, and an ADP-ribosyltransferase (ADPRT) domain at their C-termini, which
      target non-overlapping substrates. Both the GAP and the ADPRT domains contribute
      to ExoT's cytotoxicity in target epithelial cells, whereas, ExoS-induced
      apoptosis is reported to be primarily due to its ADPRT domain. In this report, we
      demonstrate that ExoS/GAP domain is both necessary and sufficient to induce
      mitochondrial apoptosis. Our data demonstrate that intoxication with ExoS/GAP
      domain leads to enrichment of Bax and Bim into the mitochondrial outer-membrane,
      disruption of mitochondrial membrane and release of and cytochrome c into the
      cytosol, which activates initiator caspase-9 and effector caspase-3, that
      executes cellular death. We posit that the contribution of the GAP domain in ExoS
      induced apoptosis was overlooked in prior studies due to its slower kinetics of
      cytotoxicity as compared to ADPRT. Our data clarify the field and reveal a novel
      virulence function for ExoS/GAP as an inducer of apoptosis.

PMID- 30232374
TI  - Electrochemical detection of dopamine using periodic cylindrical gold
      nanoelectrode arrays.
AB  - Dopamine is a key molecule in neurotransmission and has been known to be
      responsible for several neurological diseases. Hence, its sensitive and selective
      detection is important for the early diagnosis of diseases related to abnormal
      levels of dopamine. In this study, we reported a new cylindrical gold
      nanoelectrode (CAuNE) platform fabricated via sequential laser interference
      lithography and electrochemical deposition. Among the fabricated electrodes,
      CAuNEs with a diameter of 700 nm, 150 s deposited, was found to be the best for
      electrochemical dopamine detection. According to cyclic voltammetry results, the
      linear range of the CAuNE-700 nm was 1-100 uM of dopamine with a limit of
      detection (LOD) of 5.83 uM. Moreover, owing to the homogeneous periodic features
      of CAuNEs, human neural cells were successfully cultured and maintained for more
      than 5 days in vitro without the use of any extracellular matrix proteins and
      dopamine was detectable in the presence of these cells on the electrode.
      Therefore, we concluded that the developed dopamine sensing platform CAuNE can be
      used for many applications including early diagnosis of neurological diseases;
      function tests of dopaminergic neurons derived from various stem cell sources;
      and toxicity assessments of drugs, chemicals, and nanomaterials on human neuronal
      cells.

PMID- 30232375
TI  - Loss of mitochondrial calcium uniporter rewires skeletal muscle metabolism and
      substrate preference.
AB  - Skeletal muscle mitochondria readily accumulate Ca2+ in response to SR store
      releasing stimuli thanks to the activity of the mitochondrial calcium uniporter
      (MCU), the highly selective channel responsible for mitochondrial Ca2+ uptake.
      MCU positively regulates myofiber size in physiological conditions and
      counteracts pathological loss of muscle mass. Here we show that skeletal muscle
      specific MCU deletion inhibits myofiber mitochondrial Ca2+ uptake, impairs muscle
      force and exercise performance, and determines a slow to fast switch in MHC
      expression. Mitochondrial Ca2+ uptake is required for effective glucose
      oxidation, as demonstrated by the fact that in muscle-specific MCU-/- myofibers
      oxidative metabolism is impaired and glycolysis rate is increased. Although
      defective, mitochondrial activity is partially sustained by increased fatty acid
      (FA) oxidation. In MCU-/- myofibers, PDP2 overexpression drastically reduces FA
      dependency, demonstrating that decreased PDH activity is the main trigger of the
      metabolic rewiring of MCU-/- muscles. Accordingly, PDK4 overexpression in
      MCUfl/fl myofibers is sufficient to increase FA-dependent respiration. Finally,
      as a result of the muscle-specific MCU deletion, a systemic catabolic response
      impinging on both liver and adipose tissue metabolism occurs.

PMID- 30232376
TI  - Correction: Neonatal Resuscitation and Adaptation Score vs Apgar: newborn
      assessment and predictive ability.
AB  - Since the publication of the above article, the authors have noted that the name
      of the first Item in the NRAS scoring system in Figure 1 was omitted. It is Heart
      Rate (C1). The authors apologise for any inconvenience caused by this error. The
      html and online pdf versions have now been rectified and carry the corrected
      Figure.

PMID- 30232377
TI  - Analysis of peak inflating pressure and inflating pressure limit during neonatal
      volume guaranteed ventilation.
AB  - OBJECTIVES: To report how peak inflating pressure (PIP), tidal volume (VT) and
      low-tidal volume alarms are affected by maximum allowed inflating pressure (Pmax)
      during volume guarantee (VG) ventilation. STUDY DESIGN: Ventilation data were
      analysed with 1 Hz sampling rate from 25 neonates receiving synchronised
      intermittent positive pressure ventilation with VG for >12 h. RESULTS: The
      difference between Pmax and PIP (Pdiff) ranged between 5 and 20 mbar (median = 11
      mbar) despite a protocol to keep Pmax 5 mbar above the "working PIP". Pmax was
      reached in 5.2% of inflations. Computational modelling demonstrated that had
      Pdiff been kept at 5 mbar more consistently, >10% of inflations would have
      reached Pmax. The frequency of low-tidal volume alarms showed inverse correlation
      with Pdiff. CONCLUSIONS: It is difficult to implement a simple Pmax strategy due
      to variability of PIP. Setting Pmax close to the "working PIP" limits VT delivery
      and triggers frequent alarms.

PMID- 30232378
TI  - Pestiocandin, a new papulacandin class antibiotic isolated from Pestalotiopsis
      humus.
AB  - Secondary metabolites of microorganisms have proven to be an excellent source of
      drugs. We isolated a new antibiotic, named pestiocandin (1), from a culture broth
      of a filamentous fungus, Pestalotiopsis humus FKI-7473, using a multidrug
      sensitive budding yeast, S. cerevisiae 12geneDelta0HSR-iERG6. The structure of 1
      was elucidated by various NMR studies. All geometric isomerisms of 1 were shown
      to be the E-form and two pyranose units of 1 were found to be glucose and
      galactose types. Compound 1 showed weak growth inhibition against Gram-positive
      and Gram-negative bacteria, yeasts and a filamentous fungus. It displayed more
      potent growth inhibition against multidrug-sensitive yeasts than wild-type
      yeasts.

PMID- 30232379
TI  - Heterogeneity of hard skin layer in wrinkled PDMS surface fabricated by Ar ion
      beam irradiation.
AB  - The spatial distribution of binding states in the depth direction of a soft
      polydimethylsiloxane (PDMS) material was investigated in the hard skin layer
      formed by Ar ion-beam irradiation. The hard skin layer, typically considered
      silica-like and homogeneous, was heterogeneous, comprising a topmost layer and an
      intermediate layer. Impinging Ar ions transferred energy to the PDMS medium by
      collisional energy transfer, which was maximised at the surface and decreased
      gradually as the ions penetrated the PDMS. The decreasing energy transfer rate
      from the surface created a heterogeneous hard skin layer. X-ray photoelectron
      spectroscopic depth profiling showed the existence of the topmost and
      intermediate layers. In the topmost layer, scission and cross-linking occurred
      simultaneously; Si-O bonds showed the dissociated state of SiOx (x = 1.25-1.5).
      Under the topmost layer, the intermediate layer showed mostly cross-linking, with
      Si-O bonds showing silica-like binding states of SiOx (x = 1.75-2). The spatial
      distribution of carbon-related bonds such as C-Si and sp3 C-C also showed
      heterogeneity, yielding a gradient of bond distribution. A theoretical analysis
      of the collisional energy transfer rate and displacement per atom showed
      consistency with the XPS depth profiling results.

PMID- 30232380
TI  - Exciton Diffusion in Organic Nanofibers: A Monte Carlo Study on the Effects of
      Temperature and Dimensionality.
AB  - Organic nanofibers have found various applications in optoelectronic devices. In
      such devices, exciton diffusion is a major aspect concerning their efficiency. In
      the case of singlet excitons, Forster transfer is the mechanism responsible for
      this process. Temperature and morphology are factors known to influence exciton
      diffusion but are not explicitly considered in the expressions for the Forster
      rate. In this work, we employ a Kinetic Monte Carlo (KMC) model to investigate
      singlet exciton diffusion in para-hexaphenyl (P6P) and alpha-sexithiophene (6T)
      nanofibers. Building from previous experimental and theoretical studies that
      managed to obtain temperature dependent values for Forster radii, exciton average
      lifetimes and intermolecular distances, our model is able to indicate how these
      parameters translate into diffusion coefficients and diffusion lengths. Our
      results indicate that these features strongly depend on the coordination number
      in the material. Furthermore, we show how all these features influence the
      emitted light color in systems composed of alternating layers of P6P and 6T.
      Finally, we present evidence that the distribution of exciton displacements may
      result in overestimation of diffusion lengths in experimental setups.

PMID- 30232382
TI  - Author Correction: A new artificial diet for western corn rootworm larvae is
      compatible with and detects resistance to all current Bt toxins.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30232381
TI  - Haploinsufficiency of vascular endothelial growth factor related signaling genes
      is associated with tetralogy of Fallot.
AB  - PURPOSE: To determine disease-associated single-gene variants in conotruncal
      defects, particularly tetralogy of Fallot (TOF). METHODS: We analyzed for rare
      loss-of-function and deleterious variants in FLT4 (VEGFR3) and other genes in the
      vascular endothelial growth factor (VEGF) pathway, as part of a genome sequencing
      study involving 175 adults with TOF from a single site. RESULTS: We identified
      nine (5.1%) probands with novel FLT4 variants: seven loss-of-function, including
      an 8-kb deletion, and two predicted damaging. In ten other probands we found
      likely disruptive variants in VEGF-related genes: KDR (VEGFR2; two stopgain and
      two nonsynonymous variants), VEGFA, FGD5, BCAR1, IQGAP1, FOXO1, and PRDM1.
      Detection of VEGF-related variants (19/175, 10.9%) was associated with an
      increased prevalence of absent pulmonary valve (26.3% vs. 3.4%, p < 0.0001) and
      right aortic arch (52.6% vs. 29.1%, p = 0.029). Extracardiac anomalies were rare.
      In an attempt to replicate findings, we identified three loss-of-function or
      damaging variants in FLT4, KDR, and IQGAP1 in ten independent families with TOF.
      CONCLUSION: Loss-of-function variants in FLT4 and KDR contribute substantially to
      the genetic basis of TOF. The findings support dysregulated VEGF signaling as a
      novel mechanism contributing to the pathogenesis of TOF.

PMID- 30232383
TI  - MicroRNA-194-5p Levels Decrease during Deep Hypothermic Circulatory Arrest.
AB  - Hypothermia has been reported to be effective in protecting the brain in various
      clinical conditions, including resuscitation after cardiac arrest and complex
      cardiovascular surgery, and is considered to be a promising therapy for stroke.
      The present study aimed to confirm the pivotal role that miRNA-194-5p plays in
      deep hypothermia circulation arrest. On the basis of reductions in expression of
      miR-194-5p in the circulation of 21 aortic dissection patients who underwent deep
      hypothermia circulatory arrest, the specific expression, target, and function of
      miR-194-5p was investigated using primary neuron culture, polymerase chain
      reaction, in situ hybridization, and flow cytometry methods. Our results showed
      that miR-194-5p expression was significantly downregulated in hypothermia oxygen
      glucose deprivation-treated neurons in vitro. Cortical neurons transfected with
      miR-194-5p mimic exhibited increased death due to oxygen-glucose deprivation. MiR
      194-5p mediated the regulation of neuronal death, which involves the
      downregulation of the specific target protein SUMO2, which is crucial to ischemia
      tolerance. Collectively, these data highlight the unique role of miR-194-5p in
      mediating the deep hypothermia circulation arrest response via the regulation of
      SUMO2. These findings suggest that miR-194-5p could be a potential therapeutic
      target for intervention in ischemic disease.

PMID- 30232384
TI  - Tau folds differently between diseases.

PMID- 30232385
TI  - Correction: Increasing the bactofection capacity of a mammalian expression vector
      by removal of the f1 ori.
AB  - This Article was originally published with one of the panels in Figure 5A
      inserted twice (SL-pEGFP). In Figure 5B there was also a typo. SL-LacZ should
      have read SL-pEGFP(-f1). Both 5A and 5B are corrected in both the PDF and HTML
      versions of the Article.

PMID- 30232386
TI  - Effects of ocean warming and coral bleaching on aerosol emissions in the Great
      Barrier Reef, Australia.
AB  - It is proposed that emissions of volatile sulfur compounds by coral reefs
      contribute to the formation of a biologically-derived feedback on sea surface
      temperature (SST) through the formation of marine biogenic aerosol (MBA). The
      direction and strength of this feedback remains uncertain and constitutes a
      fundamental constraint on predicting the ability of corals to cope with future
      ocean warming. We investigate the effects of elevated SST and irradiance on
      satellite-derived fine-mode aerosol optical depth (AOD) throughout the Great
      Barrier Reef, Australia (GBR) over an 18-year time period. AOD is positively
      correlated with SST and irradiance and increases two-fold during spring and
      summer with high frequency variability. As the influence of non-biogenic and
      distant aerosol sources are found to be negligible, the results support recent
      findings that the 2,300 km stretch of coral reefs can be a substantial source of
      biogenic aerosol and thus, influence local ocean albedo. Importantly however, a
      tipping point in the coral stress response is identified, whereby thermal stress
      reaches a point that exceeds the capacity of corals to influence local
      atmospheric properties. Beyond this point, corals may become more susceptible to
      permanent damage with increasing stress, with potential implications for mass
      coral bleaching events.

PMID- 30232387
TI  - Expanding Greenland seagrass meadows contribute new sediment carbon sinks.
AB  - The loss of natural carbon sinks, such as seagrass meadows, contributes to
      grenhouse gas emissions and, thus, global warming. Whereas seagrass meadows are
      declining in temperate and tropical regions, they are expected to expand into the
      Arctic with future warming. Using paleoreconstruction of carbon burial and
      sources of organic carbon to shallow coastal sediments of three Greenland
      seagrass (Zostera marina) meadows of contrasting density and age, we test the
      hypothesis that Arctic seagrass meadows are expanding along with the associated
      sediment carbon sinks. We show that sediments accreted before 1900 were highly
      13C depleted, indicative of low inputs of seagrass carbon, whereas from 1940's to
      present carbon burial rates increased greatly and sediment carbon stocks were
      largely enriched with seagrass material. Currently, the increase of seagrass
      carbon inputs to sediments of lush and dense meadows (Kapisillit and Ameralik)
      was 2.6 fold larger than that of sparse meadows with low biomass (Kobbefjord).
      Our results demonstrate an increasing important role of Arctic seagrass meadows
      in supporting sediment carbon sinks, likely to be enhanced with future Arctic
      warming.

PMID- 30232388
TI  - Publisher Correction: Antiretroviral Drugs Alter the Content of Extracellular
      Vesicles from HIV-1-Infected Cells.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30232389
TI  - Child Weight Gain Trajectories Linked To Oral Microbiota Composition.
AB  - Gut and oral microbiota perturbations have been observed in obese adults and
      adolescents; less is known about their influence on weight gain in young
      children. Here we analyzed the gut and oral microbiota of 226 two-year-olds with
      16S rRNA gene sequencing. Weight and length were measured at seven time points
      and used to identify children with rapid infant weight gain (a strong risk factor
      for childhood obesity), and to derive growth curves with innovative Functional
      Data Analysis (FDA) techniques. We showed that growth curves were associated
      negatively with diversity, and positively with the Firmicutes-to-Bacteroidetes
      ratio, of the oral microbiota. We also demonstrated an association between the
      gut microbiota and child growth, even after controlling for the effect of diet on
      the microbiota. Lastly, we identified several bacterial genera that were
      associated with child growth patterns. These results suggest that by the age of
      two, the oral microbiota of children with rapid infant weight gain may have
      already begun to establish patterns often seen in obese adults. They also suggest
      that the gut microbiota at age two, while strongly influenced by diet, does not
      harbor obesity signatures many researchers identified in later life stages.

PMID- 30232390
TI  - Distinct profile and prognostic impact of body composition changes in idiopathic
      pulmonary fibrosis and idiopathic pleuroparenchymal fibroelastosis.
AB  - Change in body composition with skeletal muscle wasting, a major component of
      pulmonary cachexia, is associated with mortality in chronic obstructive pulmonary
      disease and cancer. However, its relevance in interstitial lung diseases (ILDs)
      remains unclear. We hypothesized changes in body composition would be associated
      with mortality in ILDs. We measured the cross-sectional-area (ESMCSA) and muscle
      attenuation (ESMMA) of erector-spinae muscles, as determined by CT-imaging, in
      patients with idiopathic pulmonary fibrosis (IPF; n = 131) and idiopathic
      pleuroparenchymal fibroelastosis (iPPFE; n = 43) and controls. Subsequently,
      implications with prognosis were evaluated. The ESMCSA of ILD patients, but not
      ESMMA, was significantly smaller than that in controls. Lower ESMCSA with
      decreased BMI were recorded in iPPFE patients versus IPF patients, whilst IPF
      patients had decreased ESMCSA without BMI decline. Lower ESMCSA in IPF patients
      were associated with poorer prognoses. Conversely, decreased ESMMA were
      associated with worse survival in iPPFE patients. Multivariate analyses showed
      that ESMCSA in IPF and ESMMA in iPPFE were independent risk factors for
      mortality. Distinct changes in body composition had prognostic significance among
      patients with IPF and iPPFE. Lower ESMCSA and ESMMA were independently associated
      with poor prognosis in IPF and iPPFE, respectively. These results suggest values
      to measure body composition changes in managing patients with IPF and iPPFE.

PMID- 30232391
TI  - Optogenetic Peripheral Nerve Immunogenicity.
AB  - Optogenetic technologies have been the subject of great excitement within the
      scientific community for their ability to demystify complex neurophysiological
      pathways in the central (CNS) and peripheral nervous systems (PNS). The
      excitement surrounding optogenetics has also extended to the clinic with a trial
      for ChR2 in the treatment of retinitis pigmentosa currently underway and
      additional trials anticipated for the near future. In this work, we identify the
      cause of loss-of-expression in response to transdermal illumination of an
      optogenetically active peroneal nerve following an anterior compartment (AC)
      injection of AAV6-hSyn-ChR2(H134R) with and without a fluorescent reporter. Using
      Sprague Dawley Rag2-/- rats and appropriate controls, we discover optogenetic
      loss-of-expression is chiefly elicited by ChR2-mediated immunogenicity in the
      spinal cord, resulting in both CNS motor neuron death and ipsilateral muscle
      atrophy in both low and high Adeno-Associated Virus (AAV) dosages. We further
      employ pharmacological immunosuppression using a slow-release tacrolimus pellet
      to demonstrate sustained transdermal optogenetic expression up to 12 weeks. These
      results suggest that all dosages of AAV-mediated optogenetic expression within
      the PNS may be unsafe. Clinical optogenetics for both PNS and CNS applications
      should take extreme caution when employing opsins to treat disease and may
      require concurrent immunosuppression. Future work in optogenetics should focus on
      designing opsins with lesser immunogenicity.

PMID- 30232392
TI  - Light-cured polymer electrodes for non-invasive EEG recordings.
AB  - We invented the first non-metallic, self-adhesive and dry biosignalling
      electrode. The PEDOT polymer electrode changes its aggregate state and
      conductivity by a light curing procedure. The electrode can be applied as a gel
      underneath hair without shaving. With the aid of blue light, the electrode can be
      hardened within a few seconds at the desired location on the scalp. The cured
      polymer electrode is highly conductive and can be applied on a very small
      location. Unlike other EEG electrodes, our electrode does not lose conductivity
      upon drying. Furthermore, our electrode strongly bonds to skin and does not
      require any additional adhesive. Short circuits due to an outflow of gel are
      prevented with this technique. Therefore, the PEDOT polymer electrode is
      extremely well suited for applications that, up to now, have been challenging,
      such as non-invasive EEG recordings from awake and freely moving animals, EEG
      recordings from preterm babies in the neonatal intensive care unit or long-term
      recordings in the case of sleep monitoring or epilepsy diagnostics. We addressed
      two technical questions in this work. First, is the EEG recorded with polymer
      electrodes comparable to a standard EEG? Second, is it possible to record full
      band EEGs with our electrodes?

PMID- 30232393
TI  - Thiophene-based porous organic networks for volatile iodine capture and
      effectively detection of mercury ion.
AB  - A series of conjugated microporous polymers containing thiophene-moieties (SCMP
      COOH@1-3) was obtained by a homo-coupling polymerization reaction. Then the SCMP
      COOH@1-3 were directly pyrolyzed without any templates to synthesize the porous
      carbon networks, named as SCMP-600@1, 2 and 3. SCMP-600@1-3 possess moderate BET
      surface area of 362-642 m2 g-1, have a permanent porous structure and plenty of
      sulfur and oxygen units in the skeletons as effective sorption sites, and display
      a high absorption performance for iodine vapour with an uptake up to 204 wt.%. In
      addition, SCMP-COOH@1-3 polymers can be used to effectively detect mercury ion
      from ethanol-water solution. Interestingly, under the same concentration of Hg2+
      conditions, the detection ability of mercury ion of porous materials increased
      with the increase of the pore volumes and the specific surface.

PMID- 30232395
TI  - HATs off for the Lasker awardees.

PMID- 30232394
TI  - Publisher Correction: Non-specific interactions govern cytosolic diffusion of
      nanosized objects in mammalian cells.
AB  - In the version of this Article originally published, Supplementary Videos 3-5
      were incorrectly labelled; 3 should have been 5, 4 should have been 3 and 5
      should have been 4. This has now been corrected.

PMID- 30232397
TI  - Comment on the potential role of microRNAs in hypertension.

PMID- 30232396
TI  - Serralysin family metalloproteases protects Serratia marcescens from predation by
      the predatory bacteria Micavibrio aeruginosavorus.
AB  - Micavibrio aeruginosavorus is an obligate Gram-negative predatory bacterial
      species that feeds on other Gram-negative bacteria by attaching to the surface of
      its prey and feeding on the prey's cellular contents. In this study, Serratia
      marcescens with defined mutations in genes for extracellular cell structural
      components and secreted factors were used in predation experiments to identify
      structures that influence predation. No change was measured in the ability of the
      predator to prey on S. marcescens flagella, fimbria, surface layer, prodigiosin
      and phospholipase-A mutants. However, higher predation was measured on S.
      marcescens metalloprotease mutants. Complementation of the metalloprotease gene,
      prtS, into the protease mutant, as well as exogenous addition of purified
      serralysin metalloprotease, restored predation to wild type levels. Addition of
      purified serralysin also reduced the ability of M. aeruginosavorus to prey on
      Escherichia coli. Incubating M. aeruginosavorus with purified metalloprotease was
      found to not impact predator viability; however, pre-incubating prey, but not the
      predator, with purified metalloprotease was able to block predation. Finally,
      using flow cytometry and fluorescent microscopy, we were able to confirm that the
      ability of the predator to bind to the metalloprotease mutant was higher than
      that of the metalloprotease producing wild-type. The work presented in this study
      shows that metalloproteases from S. marcescens could offer elevated protection
      from predation.

PMID- 30232399
TI  - Aspirin in the prevention of preeclampsia: the conundrum of how, who and when.
AB  - Aspirin is widely used in preventing early onset preeclampsia in women who are
      identified as being high risk. Although the benefit of aspirin is increasingly
      evident and acknowledged, there remains many unanswered questions with regards to
      its optimal application in pregnancy. The issues mainly centre around the
      relatively modest risk reduction that is observed with the use of aspirin
      prophylactically. We aim to explore the reasons behind the conservative rate of
      benefit and aim to explore factors that are likely to influence the outcomes with
      the use of aspirin.

PMID- 30232398
TI  - Antihypertensive therapy in acute ischemic stroke: where do we stand?
AB  - Despite the proven benefits of strict blood pressure (BP) control on primary and
      secondary prevention of stroke, management of acute hypertensive response in the
      early post-stroke period is surrounded by substantial controversy. Observational
      studies showed that raised BP on ischemic stroke onset is prognostically
      associated with excess risk for early adverse events and mortality. By contrast,
      randomized controlled trials and recent meta-analyses showed that although
      antihypertensive therapy effectively controls elevated BP in the acute stage of
      ischemic stroke, this BP-lowering effect is not translated into improvement in
      the risk of death or dependency. On this basis, acute and aggressive BP responses
      within 24 h of stroke onset should be avoided and antihypertensive therapy is
      recommended only for patients presenting with acute ischemic stroke and BP >
      220/120 mmHg or those with BP > 185/110 mmHg who are eligible for therapy with
      intravenous tissue plasminogen activator. By contrast, recent clinical trials
      showed that intensive BP lowering to levels < 140 mmHg for systolic BP is safe
      and lowers the risk of hematoma expansion in patients with acute intra-cerebral
      hemorrhage and this BP target is recommended by current international guidelines.
      Herein, we provide an overview of randomized trials and recent meta-analyses on
      the management of hypertension during the acute stage of ischemic stroke. We
      discuss several areas of uncertainty and conclude with perspectives for future
      research.

PMID- 30232400
TI  - Increased expression of miR-33a in monocytes from Mexican hypertensive patients
      in elevated carotid intima-media thickness.
AB  - miR-33a has been described as a key regulator in the initiation and progression
      of atherosclerosis. However, its role in arterial hypertension (HTA) has not been
      elucidated. Therefore, the aim of this study was to determine the association
      between the expression of miR-33a (5p and 3p) and the carotid intima-media
      thickness (cIMT) in samples of monocytes and serum from hypertensive patients.
      The miR-33a-5p and miR-33a-3p expression in monocytes and serum from Mexican
      hypertensive patients were examined by RT-PCR. This study involved 84 subjects
      (42 normotensive subjects and 42 patients with essential hypertension). Our study
      revealed that miR-33a-5p expression was significantly upregulated in the
      monocytes of hypertensive patients compared with the control group (p = 0.001),
      while miR-33a-3p was significantly downregulated (p = 0.013). miR-33a-5p
      upregulation [OR: 5.53, 95% CI: 2.01-15.20; p = 0.001], as well as miR-33a-3p
      downregulation [OR: 3.32, 95% CI: 1.45-7.60; p = 0.004] in monocytes, was
      associated with an increased risk of developing hypertension. In addition, miR
      33a-5p upregulation in hypertensive patients was associated with an increased
      risk of presenting cIMT [OR: 5.99, 95% CI: 1.10-32.85; p = 0.039]. Moreover, we
      found no significant differences in the expression of both strands of miR-33a in
      serum of our patients. Our results showed an upregulation of miR-33a-5p and
      downregulation of miR-33a-3p in monocytes, these data are associated with cIMT,
      which could be a risk factor for the development of hypertension. In addition,
      upregulation of miR-33a-5p in monocytes from Mexican hypertensive patients could
      be involved in the development of atherosclerosis.

PMID- 30232401
TI  - Validation of the PHYSIO-PORT UP ambulatory blood pressure monitor in pregnant
      women according to the European Society of Hypertension International Protocol
      revision 2010.
AB  - The present study examines the performance of the ambulatory blood pressure
      monitor PHYSIO-PORT UP in pregnant and preeclamptic women. The systolic blood
      pressure (SBP) and the diastolic blood pressure (DBP) of 33 subjects (among them
      13 with preeclampsia) were sequentially measured and compared to reference
      measurements. Those reference measurements were taken by two observers using a
      mercury sphygmomanometer. Subject recruitment and evaluation of the measurement
      results were performed according to the European Society of Hypertension
      International Protocol revision 2010 (ESH-IP 2010). Three readings were recorded
      per subject under static conditions. The protocol did not include testing under
      ambulatory conditions. 87/90 (SBP/DBP) of the 99 readings had a difference <= 5
      mmHg, 96/98 had a difference 98 <= 10 mmHg, and 98/99 had a difference <= 15
      mmHg. 2 out of 3 readings <= 5 mmHg was achieved by 31/32 subjects. None of the
      subjects had less than 1 comparative reading <= 5 mmHg. In conclusion, the PHYSIO
      PORT UP fulfilled all requirements of the ESH-IP 2010. According to these
      results, the PHYSIO-PORT UP can be recommended for blood pressure measurement in
      pregnant women.

PMID- 30232402
TI  - Detection of Novel duck reovirus (NDRV) using visual reverse transcription loop
      mediated isothermal amplification (RT-LAMP).
AB  - Here we present a visual reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) assay for detecting the gene encoding the sigmaB major
      outer-capsid protein of novel duck reovirus (NDRV). A set of primers, composed of
      two outer primers, two inner primers and two loop primers, was designed based on
      the gene of interest. The LAMP reaction was conducted in a traditional laboratory
      water bath at 65  degrees C for 50 min. We compared the performance of
      calcein/Mn2+ and SYBR Green I dyes, as well as electrophoresis on agarose gel
      stained with GoldView nucleic acid dye to detect the RT-LAMP-amplified products
      and all assays could be employed to discriminate between positive and negative
      specimens in visible or UV light. Our data showed that there is no cross-reaction
      with other viruses and the RT-LAMP technique displayed high sensitivity for
      detecting NDRV with a minimal detection limit of 200 fg RNA input. This assay was
      more sensitive than conventional PCR in detecting NDRV both in natural and
      experimental infection. In conclusion, the RT-LAMP technique was remarkably
      sensitive, specific, rapid, simple and profitable for the identification of NDRV.

PMID- 30232403
TI  - Proteomics study of human cord blood reticulocyte-derived exosomes.
AB  - Reticulocyte-derived exosomes (Rex), extracellular vesicles of endocytic origin,
      were initially discovered as a cargo-disposal mechanism of obsolete proteins in
      the maturation of reticulocytes into erythrocytes. In this work, we present the
      first mass spectrometry-based proteomics of human Rex (HuRex). HuRex were
      isolated from cultures of human reticulocyte-enriched cord blood using different
      culture conditions and exosome isolation methods. The newly described proteome
      consists of 367 proteins, most of them related to exosomes as revealed by gene
      ontology over-representation analysis and include multiple transporters as well
      as proteins involved in exosome biogenesis and erythrocytic disorders.
      Immunoelectron microscopy validated the presence of the transferrin receptor.
      Moreover, functional assays demonstrated active capture of HuRex by mature
      dendritic cells. As only seven proteins have been previously associated with
      HuRex, this resource will facilitate studies on the role of human reticulocyte
      derived exosomes in normal and pathological conditions affecting erythropoiesis.

PMID- 30232404
TI  - TGF-beta1 promotes expression of fibrosis-related genes through the induction of
      histone variant H3.3 and histone chaperone HIRA.
AB  - Renal fibrosis is a histological manifestation that occurs in almost every type
      of chronic kidney disease. Histone variant H3.3 and its chaperone, histone cell
      cycle regulation defective homolog A (HIRA), serve as epigenetic marks that
      regulate transcriptional activity. In this study, we assessed the roles of
      histone H3.3 and HIRA in unilateral ureteral-obstruction (UUO) mice. In UUO mice,
      the levels of histone H3.3 and HIRA were significantly upregulated in the
      kidneys. These upregulated levels were decreased by a TGF-beta1 neutralizing
      antibody. TGF-beta1 induced histone H3.3 and HIRA expression in vitro via a Smad3
      dependent pathway in normal rat kidney (NRK)-52E cells. Additionally, knockdown
      of HIRA expression decreased histone H3.3 expression and fibrogenesis in NRK-52E
      cells after TGF-beta1 stimulation. Chromatin immunoprecipitation analysis
      revealed that promoters of fibrosis-related genes were immunoprecipitated with
      both histone H3.3 and HIRA in NRK-52E cells. Lastly, in human kidney biopsies
      from patients diagnosed with IgA nephropathy, histone H3.3 and HIRA
      immunostaining correlated positively with areas of fibrosis and estimated
      glomerular filtration rate. In conclusion, TGF-beta1 induces expression of
      histone H3.3 and HIRA, which regulates expression of fibrosis-related genes.

PMID- 30232405
TI  - Exploration and application of a highly sensitive bis(salamo)-based fluorescent
      sensor for B4O72- in water-containing systems and living cells.
AB  - A highly selective fluorescent sensor H4L based on a bis(salamo)-type compound
      with two N2O2 chelating moieties as ionophore was successfully developed. Sensor
      H4L was found to have excellent selectivity for B4O72- over many other anions (Br
      , CI-, CN-, CO32-, HCO3-, H2PO4-, HSO4-, NO3-, OAc-, S2O3-, SCN-, SO42-, Hcy
      (homocysteine) and H2O2), and it exhibited an approximately 150-fold enhancement
      of the fluorescence response to B4O72- in Tris-HCl buffer (DMF/H2O = 9:1, v/v, pH
      = 7) solutions. Significantly, its fluorescence intensity was enhanced in a
      linear fashion with increasing concentrations of B4O72-. The detection limit of
      sensor H4L towards B4O72- was 8.61 * 10-7 M. The test strips could conveniently,
      efficiently and simply detect B4O72- ions in Tris-HCl buffer (DMF/H2O = 9:1, v/v,
      pH = 7) solutions. Furthermore, sensor H4L showed excellent membrane permeability
      in living cells, and it was successfully used to monitor intracellular B4O72- by
      confocal luminescence imaging.

PMID- 30232407
TI  - Tinkering with THC-to-CBD ratios in Marijuana.

PMID- 30232406
TI  - Cell-based RNAi screening and high-content analysis in primary calvarian
      osteoblasts applied to identification of osteoblast differentiation regulators.
AB  - Osteoblasts are responsible for the maintenance of bone homeostasis. Deregulation
      of their differentiation is etiologically linked to several bone disorders,
      making this process an important target for therapeutic intervention. Systemic
      identification of osteoblast regulators has been hampered by the unavailability
      of physiologically relevant in vitro systems suitable for efficient RNAi and for
      differentiation read-outs compatible with fluorescent microscopy-based high
      content analysis (HCA). Here, we report a new method for identification of
      osteoblast differentiation regulators by combining siRNA transfection in
      physiologically relevant cells with high-throughput screening (HTS). Primary
      mouse calvarial osteoblasts were seeded in 384-well format and reverse
      transfected with siRNAs and their cell number and differentiation was assayed by
      HCA. Automated image acquisition allowed high-throughput analyses and
      classification of single cell features. The physiological relevance,
      reproducibility, and sensitivity of the method were validated using known
      regulators of osteoblast differentiation. The application of HCA to siRNAs
      against expression of 320 genes led to the identification of five potential
      suppressors and 60 activators of early osteoblast differentiation. The described
      method and the associated analysis pipeline are not restricted to RNAi-based
      screening, but can be adapted to large-scale drug HTS or to small-scale targeted
      experiments, to identify new critical factors important for early
      osteoblastogenesis.

PMID- 30232408
TI  - Klotho suppresses colorectal cancer through modulation of the unfolded protein
      response.
AB  - Klotho is an anti-aging transmembrane protein, which can be shed and function as
      a hormone. Accumulating data indicate klotho as a tumor suppressor in a wide
      array of malignancies and indicate the subdomain KL1 as the active region of the
      protein. We aimed to study the role of klotho as a tumor suppressor in colorectal
      cancer. Bioinformatics analyses of TCGA datasets indicated reduced klotho mRNA
      levels in human colorectal cancer, along with negative regulation of klotho
      expression by hypermethylation of the promoter and 1st exon, and hypomethylation
      of an area within the gene. Overexpression or treatment with klotho or KL1
      inhibited proliferation of colorectal cancer cells in vitro. The in vivo activity
      of klotho and KL1 was examined using two models recapitulating development of
      tumors in the normal colonic environment of immune-competent mice. Treatment with
      klotho inhibited formation of colon polyps induced by the carcinogen
      azoxymethane, and KL1 treatment slowed growth of orthotopically-implanted
      colorectal tumors. Gene expression array revealed that klotho and KL1 expression
      enhanced the unfolded protein response (UPR) and this was further established by
      increased levels of spliced XBP1, GRP78 and phosphorylated-eIF2alpha.
      Furthermore, attenuation of the UPR partially abrogated klotho tumor suppressor
      activity. In conclusion, this study indicates klotho as a tumor suppressor in
      colorectal cancer and identifies, for the first time, the UPR as a pathway
      mediating klotho activities in cancer. These data suggest that administration of
      exogenous klotho or KL1 may serve as a novel strategy for prevention and
      treatment of colorectal cancer.

PMID- 30232410
TI  - Renal disease in tuberous sclerosis complex: pathogenesis and therapy.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized
      by hamartomatous tumours of the brain, heart, skin, lung and kidney. Patients
      with TSC show a diverse range of neurological features (including seizures,
      cognitive disability and autism) and renal manifestations (including
      angiomyolipomas, epithelial cysts and renal cell carcinoma (RCC)). TSC is caused
      by inactivating mutations in TSC1 and TSC2, which encode hamartin and tuberin,
      respectively. These two proteins form a complex that negatively regulates
      mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of
      cellular growth and metabolism. In clinical trials, allosteric inhibitors of
      mTORC1 decrease angiomyolipoma size, but the tumours regrow after treatment
      cessation. Therefore, the development of strategies to eliminate rather than
      suppress angiomyolipomas remains a high priority. This Review describes important
      advances in the TSC field and highlights several remaining critical knowledge
      gaps: the factors that promote aggressive behaviour by a subset of TSC-associated
      RCCs; the molecular mechanisms underlying early-onset cystogenesis in TSC2-PKD1
      contiguous gene deletion syndrome; the effect of early, long-term mTORC1
      inhibition on the development of TSC renal disease; and the identification of the
      cell or cells of origin of angiomyolipomas.

PMID- 30232411
TI  - Humoral immunity goes hormonal.

PMID- 30232409
TI  - An in silico down-scaling approach uncovers novel constituents of the Plasmodium
      containing vacuole.
AB  - During blood stage development the malaria parasite resides in a membrane-bound
      compartment, termed the parasitophorous vacuole (PV). The reasons for this
      intravacuolar life style and the molecular functions of this parasite-specific
      compartment remain poorly defined, which is mainly due to our limited knowledge
      about the molecular make-up of this unique niche. We used an in silico down
      scaling approach to select for Plasmodium-specific candidates that harbour
      signatures of PV residency. Live co-localisation of five endogenously tagged
      proteins confirmed expression in the PV of Plasmodium berghei blood and liver
      stages. ER retention was ruled out by addition of the respective carboxyterminal
      tetrapeptides to a secreted reporter protein. Although all five PV proteins are
      highly expressed, four proved to be dispensable for parasite development in the
      mammalian and mosquito host, as revealed by targeted gene deletion. In good
      agreement with their redundant roles, the knockout parasites displayed no
      detectable deficiencies in protein export, sequestration, or PV morphology.
      Together, our approach improved the catalogue of the Plasmodium PV proteome and
      provides experimental genetics evidence for functional redundancy of several PV
      proteins.

PMID- 30232412
TI  - Reticulocyte hemoglobin content as an early predictive biomarker of brain iron
      deficiency.
AB  - BACKGROUND: Fetal and neonatal brain iron content is compromised at the time of
      anemia, suggesting that screening for iron deficiency by measuring hemoglobin is
      inadequate to protect the brain. Reticulocyte hemoglobin (Ret-He) reflects iron
      deficient (ID) erythropoiesis prior to anemia. METHODS: At postnatal day (P), 10
      and 20 iron-sufficient rat pups were fostered to ID dams to produce a postnatal
      ID (PNID) group, which was compared to 20 iron-sufficient (IS) pups fostered by
      IS dams. Pups were assessed from P13 to P15 for hemoglobin, hematocrit,
      reticulocyte count, and Ret-He. Hippocampal iron status was assessed by
      transferrin receptor-1 (Tfrc-1) and divalent metal transporter-1 (Slc11a2) mRNA
      expression. RESULTS: At P13, brain iron status was similar between groups; only
      Ret-He was lower in the PNID group. At P14, the PNID group had lower Ret-He,
      hematocrit, mean corpuscular volume (MCV), and reticulocyte percentage (RET%).
      Tfrc-1 expression was increased, consistent with brain iron deficiency. Both Ret
      He and MCV correlated with brain iron status at P14 and P15. CONCLUSIONS: Ret-He
      was the only red cell marker affected prior to the onset of brain ID. The
      clinical practice of using anemia as the preferred biomarker for diagnosis of
      iron deficiency may need reconsidering.

PMID- 30232413
TI  - Correction: The European Society for Blood and Marrow Transplantation (EBMT)
      Consensus Guidelines for the Detection and Treatment of Donor-specific Anti-HLA
      Antibodies (DSA) in Haploidentical Hematopoietic Cell Transplantation.
AB  - The original version of this Article contained a typographical error in the
      spelling of the author Marcelo Fernandez-Vina, which was incorrectly given as
      Marcelo Fernadez-Vina. This has now been corrected in the PDF and HTML versions
      of the Article.

PMID- 30232414
TI  - Donor-specific anti-HLA antibodies in unrelated hematopoietic cell
      transplantation for non-malignant disorders.

PMID- 30232415
TI  - Intrabone transplant provides full stemness of cord blood stem cells with fast
      hematopoietic recovery and low GVHD rate: results from a prospective study.
AB  - Umbilical Cord Blood (UCB) represents a valid option for patients with
      hematopoietic malignancies lacking an HLA matched donor. To overcome the
      limitation of the low stem cell dose of UCB, the intrabone (IB) route has been
      proposed. We report the results of a prospective study on a poor-prognosis cohort
      of 23 patients receiving intrabone single UCB transplant (Clinicaltrials.gov
      NCT00886522). Cumulative incidence of hematological recovery at day 90 was 82 +/-
      9% (ANC > 0.5 * 109/L) and 70 +/- 10% (platelet > 50 * 109/L) and correlated with
      CD34 + cells in the graft. NRM was 20 +/-  9%. No severe aGVHD and only one
      extensive cGVHD occurred, with fast immune reconstitution. To test the hypothesis
      that the direct IB injection could affect the expression of stem cells regulatory
      pathways, CD34 + cells from BM aspirates at day + 10, + 20, + 30, processed in
      hypoxic conditions mimicking the BM-microenvironment (7%pO2), were studied for
      the expression of c-Mpl, Notch1 and CXCR4. We found that the expression of c-Mpl
      in CD34 + cells at day + 10 significantly correlated with hematological recovery.
      In conclusion, IB-UCB transplant success is associated with low incidence of GVHD
      and high-speed platelet recovery; intrabone route may preserve full hematopoietic
      stemness by direct delivery of UCB stem cells into the hypoxic HSC niche.

PMID- 30232416
TI  - Ghrelin is impacted by the endogenous circadian system and by circadian
      misalignment in humans.
AB  - The human circadian system regulates hunger independently of behavioral factors,
      resulting in a trough in the biological morning and a peak in the biological
      evening. However, the role of the only known orexigenic hormone, ghrelin, in this
      circadian rhythm is unknown. Furthermore, although shift work is an obesity risk
      factor, the separate effects of the endogenous circadian system, the behavioral
      cycle, and circadian misalignment on ghrelin has not been systematically studied.
      Here we show-by using two 8-day laboratory protocols-that circulating active
      (acylated) ghrelin levels are significantly impacted by endogenous circadian
      phase in healthy adults. Active ghrelin levels were higher in the biological
      evening than the biological morning (fasting +15.1%, P = 0.0001; postprandial
      +10.4%, P = 0.0002), consistent with the circadian variation in hunger (P =
      0.028). Moreover, circadian misalignment itself (12-h behavioral cycle inversion)
      increased postprandial active ghrelin levels (+5.4%; P = 0.04). While not
      significantly influencing hunger (P > 0.08), circadian misalignment increased
      appetite for energy-dense foods (all P < 0.05). Our results provide possible
      mechanisms for the endogenous circadian rhythm in hunger, as well as for the
      increased risk of obesity among shift workers.

PMID- 30232417
TI  - Prenatal smoking exposure and cardio-metabolic risk factors in adulthood: a
      general population study and a meta-analysis.
AB  - OBJECTIVE: Prenatal smoking exposure is associated with obesity and other cardio
      metabolic risk factors in children, but no previous meta-analysis has been
      conducted in adults. METHODS: We investigated the association of prenatal smoking
      exposure in the Danish General Suburban Population Study (GESUS) with BMI, waist
      circumference, total cholesterol, type 2 diabetes, gestational type 2 diabetes,
      and hypertension in adulthood. We subsequently performed a meta-analysis, adding
      published studies investigating the association between prenatal smoking and the
      risk of cardio-metabolic outcomes among individuals at least 18 years of age.
      RESULTS: We included 19 eligible observational studies with various cardio
      metabolic outcomes (N = 24,201-308,981 adults). In individuals exposed to
      prenatal smoking, the pooled random effects adjusted odds ratio were 1.35 (95%
      CI: 1.16-1.56) for being overweight, 1.46 (1.39-1.54) for being obese, 1.07 (0.89
      1.29) for type 2 diabetes, 1.17 (0.92-1.48) for hypertension, and 1.38 (1.19
      1.61) for gestational diabetes mellitus (GDM), compared with no exposure. The
      standardized means in waist circumference, total cholesterol, diastolic, and
      systolic blood pressure were not different in individuals exposed vs. not exposed
      to prenatal smoking. Heterogeneity was moderate to high (51% < I2 < 99%).
      However, removal of the high heterogeneity removed the associated uncertainty in
      the point estimate and revealed that prenatal smoking is associated with
      increased BMI in adulthood. There was also no evidence of publication bias in the
      meta-analyses. CONCLUSIONS: The findings from the meta-analyses suggested that
      prenatal smoking exposure is associated with an increased odds ratio of
      overweight, obesity, and GDM in adulthood, but not with type 2 diabetes,
      hypertension, waist circumference, or total cholesterol. These findings highlight
      the importance of abstaining from smoking by pregnant women.

PMID- 30232418
TI  - Integrating genetic, transcriptional, and biological information provides
      insights into obesity.
AB  - OBJECTIVE: Indices of body fat distribution are heritable, but few genetic
      signals have been reported from genome-wide association studies (GWAS) of
      computed tomography (CT) imaging measurements of body fat distribution. We aimed
      to identify genes associated with adiposity traits and the key drivers that are
      central to adipose regulatory networks. SUBJECTS: We analyzed gene transcript
      expression data in blood from participants in the Framingham Heart Study, a large
      community-based cohort (n up to 4303), as well as implemented an integrative
      analysis of these data and existing biological information. RESULTS: Our
      association analyses identified unique and common gene expression signatures
      across several adiposity traits, including body mass index, waist-hip ratio,
      waist circumference, and CT-measured indices, including volume and quality of
      visceral and subcutaneous adipose tissues. We identified six enriched KEGG
      pathways and two co-expression modules for further exploration of adipose
      regulatory networks. The integrative analysis revealed four gene sets (Apoptosis,
      p53 signaling pathway, Proteasome, Ubiquitin-mediated proteolysis) and two co
      expression modules with significant genetic variants and 94 key drivers/genes
      whose local networks were enriched with adiposity-associated genes, suggesting
      that these enriched pathways or modules have genetic effects on adiposity. Most
      identified key driver genes are involved in essential biological processes such
      as controlling cell cycle, DNA repair, and degradation of regulatory proteins are
      cancer related. CONCLUSIONS: Our integrative analysis of genetic,
      transcriptional, and biological information provides a list of compelling
      candidates for further follow-up functional studies to uncover the biological
      mechanisms underlying obesity. These candidates highlight the value of examining
      CT-derived and central adiposity traits.

PMID- 30232419
TI  - Maternal body mass index, gestational weight gain, and childhood abdominal,
      pericardial, and liver fat assessed by magnetic resonance imaging.
AB  - BACKGROUND/OBJECTIVES: Maternal obesity and excessive gestational weight gain are
      associated with an increased risk of obesity in offspring. It remains unclear
      whether maternal adiposity also affects organ fat, which has important adverse
      cardiometabolic health consequences and whether the associations reflect
      intrauterine causal mechanisms. We examined the associations of parental pre
      pregnancy body mass index (BMI) and gestational weight gain with general,
      abdominal, pericardial, and liver fat in 10-year-old children. SUBJECTS/METHODS:
      In a population-based prospective cohort study among 2354 parents and their
      children, we obtained pre-pregnancy maternal and paternal BMI and gestational
      weight gain and offspring BMI, fat mass index (total fat/height4) by dual-energy
      X-ray absorptiometry, and subcutaneous fat index (subcutaneous fat/height4),
      visceral fat index (visceral fat/height3), pericardial fat index (pericardial
      fat/height3), and liver fat fraction by magnetic resonance imaging (MRI) at 10
      years. RESULTS: A 1-standard deviation score (SDS) higher maternal pre-pregnancy
      BMI was associated with higher childhood BMI (difference 0.32 (95% confidence
      interval (CI) 0.28, 0.36) SDS), fat mass index (difference 0.28 (95% CI 0.24,
      0.31) SDS), subcutaneous fat index (difference 0.26 (95% CI 0.22, 0.30) SDS),
      visceral fat index (difference 0.24 (95% CI 0.20, 0.28) SDS), pericardial fat
      index (difference 0.12 (95% CI 0.08, 0.16) SDS), and liver fat fraction
      (difference 0.15 (95% CI 0.11, 0.19) SDS). After conditioning each MRI adiposity
      measure on BMI at 10 years, higher maternal pre-pregnancy BMI remained associated
      with higher childhood subcutaneous and visceral fat indices. Smaller but not
      statistically different effect estimates were observed for paternal BMI.
      Gestational weight gain was not consistently associated with organ fat.
      CONCLUSIONS: Higher maternal pre-pregnancy BMI, but not gestational weight gain,
      was associated with higher general and organ fat. Similar associations of pre
      pregnancy maternal and paternal BMI with offspring adiposity suggest a role of
      family shared lifestyle factors and genetics.

PMID- 30232420
TI  - Ice loss from the East Antarctic Ice Sheet during late Pleistocene interglacials.
AB  - Understanding ice sheet behaviour in the geological past is essential for
      evaluating the role of the cryosphere in the climate system and for projecting
      rates and magnitudes of sea level rise in future warming scenarios1-4. Although
      both geological data5-7 and ice sheet models3,8 indicate that marine-based
      sectors of the East Antarctic Ice Sheet were unstable during Pliocene warm
      intervals, the ice sheet dynamics during late Pleistocene interglacial intervals
      are highly uncertain3,9,10. Here we provide evidence from marine sedimentological
      and geochemical records for ice margin retreat or thinning in the vicinity of the
      Wilkes Subglacial Basin of East Antarctica during warm late Pleistocene
      interglacial intervals. The most extreme changes in sediment provenance,
      recording changes in the locus of glacial erosion, occurred during marine isotope
      stages 5, 9, and 11, when Antarctic air temperatures11 were at least two degrees
      Celsius warmer than pre-industrial temperatures for 2,500 years or more. Hence,
      our study indicates a close link between extended Antarctic warmth and ice loss
      from the Wilkes Subglacial Basin, providing ice-proximal data to support a
      contribution to sea level from a reduced East Antarctic Ice Sheet during warm
      interglacial intervals. While the behaviour of other regions of the East
      Antarctic Ice Sheet remains to be assessed, it appears that modest future warming
      may be sufficient to cause ice loss from the Wilkes Subglacial Basin.

PMID- 30232421
TI  - Absolute timing of the photoelectric effect.
AB  - Photoemission spectroscopy is central to understanding the inner workings of
      condensed matter, from simple metals and semiconductors to complex materials such
      as Mott insulators and superconductors1. Most state-of-the-art knowledge about
      such solids stems from spectroscopic investigations, and use of subfemtosecond
      light pulses can provide a time-domain perspective. For example, attosecond (10
      18 seconds) metrology allows electron wave packet creation, transport and
      scattering to be followed on atomic length scales and on attosecond timescales2
      7. However, previous studies could not disclose the duration of these processes,
      because the arrival time of the photons was not known with attosecond precision.
      Here we show that this main source of ambiguity can be overcome by introducing
      the atomic chronoscope method, which references all measured timings to the
      moment of light-pulse arrival and therefore provides absolute timing of the
      processes under scrutiny. Our proof-of-principle experiment reveals that
      photoemission from the tungsten conduction band can proceed faster than
      previously anticipated. By contrast, the duration of electron emanation from core
      states is correctly described by semiclassical modelling. These findings
      highlight the necessity of treating the origin, initial excitation and transport
      of electrons in advanced modelling of the attosecond response of solids, and our
      absolute data provide a benchmark. Starting from a robustly characterized
      surface, we then extend attosecond spectroscopy towards isolating the emission
      properties of atomic adsorbates on surfaces and demonstrate that these act as
      photoemitters with instantaneous response. We also find that the tungsten core
      electron timing remains unchanged by the adsorption of less than one monolayer of
      dielectric atoms, providing a starting point for the exploration of excitation
      and charge migration in technologically and biologically relevant adsorbate
      systems.

PMID- 30232422
TI  - Decoding the phase structure of QCD via particle production at high energy.
AB  - Recent studies based on lattice Monte Carlo simulations of quantum chromodynamics
      (QCD)-the theory of strong interactions-have demonstrated that at high
      temperature there is a phase change from confined hadronic matter to a deconfined
      quark-gluon plasma in which quarks and gluons can travel distances that greatly
      exceed the size of hadrons. Here we show that the phase structure of such
      strongly interacting matter can be decoded by analysing particle production in
      high-energy nuclear collisions within the framework of statistical hadronization,
      which accounts for the thermal distribution of particle species. Our results
      represent a phenomenological determination of the location of the phase boundary
      of strongly interacting matter, and imply quark-hadron duality at this boundary.

PMID- 30232423
TI  - Conflicting evidence for HIV enrichment in CD32+ CD4 T cells.

PMID- 30232424
TI  - Evidence that CD32a does not mark the HIV-1 latent reservoir.

PMID- 30232426
TI  - Descours et al. reply.

PMID- 30232425
TI  - The role of CD32 during HIV-1 infection.

PMID- 30232427
TI  - Superstructures generated from truncated tetrahedral quantum dots.
AB  - The assembly of uniform nanocrystal building blocks into well ordered
      superstructures is a fundamental strategy for the generation of meso- and
      macroscale metamaterials with emergent nanoscopic functionalities1-10. The
      packing of spherical nanocrystals, which frequently adopt dense, face-centred
      cubic or hexagonal-close-packed arrangements at thermodynamic equilibrium, has
      been much more widely studied than that of non-spherical, polyhedral
      nanocrystals, despite the fact that the latter have intriguing anisotropic
      properties resulting from the shapes of the building blocks11-13. Here we report
      the packing of truncated tetrahedral quantum dot nanocrystals into three distinct
      superstructures-one-dimensional chiral tetrahelices, two-dimensional quasicrystal
      approximant superlattices and three-dimensional cluster-based body-centred-cubic
      single supercrystals-by controlling the assembly conditions. Using techniques in
      real and reciprocal spaces, we successfully characterized the superstructures
      from their nanocrystal translational orderings down to the atomic-orientation
      alignments of individual quantum dots. Our packing models showed that formation
      of the nanocrystal superstructures is dominated by the selective facet-to-facet
      contact induced by the anisotropic patchiness of the tetrahedra. This study
      provides information about the packing of non-spherical nanocrystals into complex
      superstructures, and may enhance the potential of self-assembled nanocrystal
      metamaterials in practical applications.

PMID- 30232429
TI  - Short proton bunches rapidly accelerate energetic electrons.

PMID- 30232430
TI  - Timing the action of light on matter.

PMID- 30232428
TI  - A dynamically young and perturbed Milky Way disk.
AB  - The evolution of the Milky Way disk, which contains most of the stars in the
      Galaxy, is affected by several phenomena. For example, the bar and the spiral
      arms of the Milky Way induce radial migration of stars1 and can trap or scatter
      stars close to orbital resonances2. External perturbations from satellite
      galaxies can also have a role, causing dynamical heating of the Galaxy3, ring
      like structures in the disk4 and correlations between different components of the
      stellar velocity5. These perturbations can also cause 'phase wrapping' signatures
      in the disk6-9, such as arched velocity structures in the motions of stars in the
      Galactic plane. Some manifestations of these dynamical processes have already
      been detected, including kinematic substructure in samples of nearby stars10-12,
      density asymmetries and velocities across the Galactic disk that differ from the
      axisymmetric and equilibrium expectations13, especially in the vertical
      direction11,14-16, and signatures of incomplete phase mixing in the
      disk7,12,17,18. Here we report an analysis of the motions of six million stars in
      the Milky Way disk. We show that the phase-space distribution contains different
      substructures with various morphologies, such as snail shells and ridges, when
      spatial and velocity coordinates are combined. We infer that the disk must have
      been perturbed between 300 million and 900 million years ago, consistent with
      estimates of the previous pericentric passage of the Sagittarius dwarf galaxy.
      Our findings show that the Galactic disk is dynamically young and that modelling
      it as time-independent and axisymmetric is incorrect.

PMID- 30232431
TI  - Don't deploy negative emissions technologies without ethical analysis.

PMID- 30232432
TI  - Biodiversity: squabbles don't obscure the bigger picture.

PMID- 30232433
TI  - Biodiversity: honour guidelines that reconcile world views.

PMID- 30232434
TI  - Biodiversity: ideas need time to mature.

PMID- 30232435
TI  - Biodiversity: sparring makes us strong.

PMID- 30232436
TI  - The 133rd Live Podcast of the Gourmando Resistance.

PMID- 30232438
TI  - Filthy air is a global disgrace.

PMID- 30232437
TI  - Reboot undergraduate courses for reproducibility.

PMID- 30232439
TI  - Austrian agency shows how to tackle scientific misconduct.

PMID- 30232441
TI  - A guide to the Nature Index.

PMID- 30232440
TI  - A new way to capture the brain's electrical symphony.

PMID- 30232442
TI  - The world at their feet.

PMID- 30232443
TI  - Predicting scientific success.

PMID- 30232445
TI  - Discovery relies on strong support staff.

PMID- 30232444
TI  - The fast track.

PMID- 30232446
TI  - Movers and shakers.

PMID- 30232447
TI  - Green shoots.

PMID- 30232449
TI  - Lab-death case, harassment rules and Luxembourg's new space agency.

PMID- 30232448
TI  - Challenger states.

PMID- 30232450
TI  - Nuclear envelope assembly defects link mitotic errors to chromothripsis.
AB  - Defects in the architecture or integrity of the nuclear envelope are associated
      with a variety of human diseases1. Micronuclei, one common nuclear aberration,
      are an origin for chromothripsis2, a catastrophic mutational process that is
      commonly observed in cancer3-5. Chromothripsis occurs after micronuclei
      spontaneously lose nuclear envelope integrity, which generates chromosome
      fragmentation6. Disruption of the nuclear envelope exposes DNA to the cytoplasm
      and initiates innate immune proinflammatory signalling7. Despite its importance,
      the basis of the fragility of the micronucleus nuclear envelope  is not known.
      Here we show that micronuclei undergo defective nuclear envelope assembly. Only
      'core' nuclear envelope proteins8,9 assemble efficiently on lagging chromosomes,
      whereas 'non-core' nuclear envelope proteins8,9, including nuclear pore complexes
      (NPCs), do not. Consequently, micronuclei fail to properly import key proteins
      that are necessary for the integrity of the nuclear envelope and genome. We show
      that spindle microtubules block assembly of NPCs and other non-core nuclear
      envelope proteins on lagging chromosomes, causing an irreversible defect in
      nuclear envelope assembly. Accordingly, experimental manipulations that position
      missegregated chromosomes away from the spindle correct defective nuclear
      envelope assembly, prevent spontaneous nuclear envelope disruption, and suppress
      DNA damage in micronuclei. Thus, during mitotic exit in metazoan cells,
      chromosome segregation and nuclear envelope assembly are only loosely coordinated
      by the timing of mitotic spindle disassembly. The absence of precise checkpoint
      controls may explain why errors during mitotic exit are frequent and often
      trigger catastrophic genome rearrangements4,5.

PMID- 30232451
TI  - Clearance of senescent glial cells prevents tau-dependent pathology and cognitive
      decline.
AB  - Cellular senescence, which is characterized by an irreversible cell-cycle arrest1
      accompanied by a distinctive secretory phenotype2, can be induced through various
      intracellular and extracellular factors. Senescent cells that express the cell
      cycle inhibitory protein p16INK4A have been found to actively drive naturally
      occurring age-related tissue deterioration3,4 and contribute to several diseases
      associated with ageing, including atherosclerosis5 and osteoarthritis6. Various
      markers of senescence have been observed in patients with neurodegenerative
      diseases7-9; however, a role for senescent cells in the aetiology of these
      pathologies is unknown. Here we show a causal link between the accumulation of
      senescent cells and cognition-associated neuronal loss. We found that the
      MAPTP301SPS19 mouse model of tau-dependent neurodegenerative disease10
      accumulates p16INK4A-positive senescent astrocytes and microglia. Clearance of
      these cells as they arise using INK-ATTAC transgenic mice prevents gliosis,
      hyperphosphorylation of both soluble and insoluble tau leading to neurofibrillary
      tangle deposition, and degeneration of cortical and hippocampal neurons, thus
      preserving cognitive function. Pharmacological intervention with a first
      generation senolytic modulates tau aggregation. Collectively, these results show
      that senescent cells have a role in the initiation and progression of tau
      mediated disease, and suggest that targeting senescent cells may provide a
      therapeutic avenue for the treatment of these pathologies.

PMID- 30232452
TI  - Hydraulic diversity of forests regulates ecosystem resilience during drought.
AB  - Plants influence the atmosphere through fluxes of carbon, water and energy1, and
      can intensify drought through land-atmosphere feedback effects2-4. The diversity
      of plant functional traits in forests, especially physiological traits related to
      water (hydraulic) transport, may have a critical role in land-atmosphere
      feedback, particularly during drought. Here we combine 352 site-years of eddy
      covariance measurements from 40 forest sites, remote-sensing observations of
      plant water content and plant functional-trait data to test whether the diversity
      in plant traits affects the response of the ecosystem to drought. We find
      evidence that higher hydraulic diversity buffers variation in ecosystem flux
      during dry periods across temperate and boreal forests. Hydraulic traits were the
      predominant significant predictors of cross-site patterns in drought response. By
      contrast, standard leaf and wood traits, such as specific leaf area and wood
      density, had little explanatory power. Our results demonstrate that diversity in
      the hydraulic traits of trees mediates ecosystem resilience to drought and is
      likely to have an important role in future ecosystem-atmosphere feedback effects
      in a changing climate.

PMID- 30232453
TI  - mRNA circularization by METTL3-eIF3h enhances translation and promotes
      oncogenesis.
AB  - N6-methyladenosine (m6A) modification of mRNA is emerging as an important
      regulator of gene expression that affects different developmental and biological
      processes, and altered m6A homeostasis is linked to cancer1-5. m6A modification
      is catalysed by METTL3 and enriched in the 3' untranslated region of a large
      subset of mRNAs at sites close to the stop codon5. METTL3 can promote translation
      but the mechanism and relevance of this process remain unknown1. Here we show
      that METTL3 enhances translation only when tethered to reporter mRNA at sites
      close to the stop codon, supporting a mechanism of mRNA looping for ribosome
      recycling and translational control. Electron microscopy reveals the topology of
      individual polyribosomes with single METTL3 foci in close proximity to 5' cap
      binding proteins. We identify a direct physical and functional interaction
      between METTL3 and the eukaryotic translation initiation factor 3 subunit h
      (eIF3h). METTL3 promotes translation of a large subset of oncogenic mRNAs
      including bromodomain-containing protein 4-that is also m6A-modified in human
      primary lung tumours. The METTL3-eIF3h interaction is required for enhanced
      translation, formation of densely packed polyribosomes and oncogenic
      transformation. METTL3 depletion inhibits tumorigenicity and sensitizes lung
      cancer cells to BRD4 inhibition. These findings uncover a mechanism of
      translation control that is based on mRNA looping and identify METTL3-eIF3h as a
      potential therapeutic target for patients with cancer.

PMID- 30232454
TI  - Ring nucleases deactivate type III CRISPR ribonucleases by degrading cyclic
      oligoadenylate.
AB  - The CRISPR system provides adaptive immunity against mobile genetic elements in
      prokaryotes, using small CRISPR RNAs that direct effector complexes to degrade
      invading nucleic acids1-3. Type III effector complexes were recently demonstrated
      to synthesize a novel second messenger, cyclic oligoadenylate, on binding target
      RNA4,5. Cyclic oligoadenylate, in turn, binds to and activates ribonucleases and
      other factors-via a CRISPR-associated Rossman-fold domain-and thereby induces in
      the cell an antiviral state that is important for immunity. The mechanism of the
      'off-switch' that resets the system is not understood. Here we identify the
      nuclease that degrades these cyclic oligoadenylate ring molecules. This 'ring
      nuclease' is itself a protein of the CRISPR-associated Rossman-fold family, and
      has a metal-independent mechanism that cleaves cyclic tetraadenylate rings to
      generate linear diadenylate species and switches off the antiviral state. The
      identification of ring nucleases adds an important insight to the CRISPR system.

PMID- 30232455
TI  - Tc toxin activation requires unfolding and refolding of a beta-propeller.
AB  - Tc toxins secrete toxic enzymes into host cells using a unique syringe-like
      injection mechanism. They are composed of three subunits, TcA, TcB and TcC. TcA
      forms the translocation channel and the TcB-TcC heterodimer functions as a cocoon
      that shields the toxic enzyme. Binding of the cocoon to the channel triggers
      opening of the cocoon and translocation of the toxic enzyme into the channel.
      Here we show in atomic detail how the assembly of the three components activates
      the toxin. We find that part of the cocoon completely unfolds and refolds into an
      alternative conformation upon binding. The presence of the toxic enzyme inside
      the cocoon is essential for its subnanomolar binding affinity for the TcA
      subunit. The enzyme passes through a narrow negatively charged constriction site
      inside the cocoon, probably acting as an extruder that releases the unfolded
      protein with its C terminus first into the translocation channel.

PMID- 30232456
TI  - Glider soaring via reinforcement learning in the field.
AB  - Soaring birds often rely on ascending thermal plumes (thermals) in the atmosphere
      as they search for prey or migrate across large distances1-4. The landscape of
      convective currents is rugged and shifts on timescales of a few minutes as
      thermals constantly form, disintegrate or are transported away by the wind5,6.
      How soaring birds find and navigate thermals within this complex landscape is
      unknown. Reinforcement learning7 provides an appropriate framework in which to
      identify an effective navigational strategy as a sequence of decisions made in
      response to environmental cues. Here we use reinforcement learning to train a
      glider in the field to navigate atmospheric thermals autonomously. We equipped a
      glider of two-metre wingspan with a flight controller that precisely controlled
      the bank angle and pitch, modulating these at intervals with the aim of gaining
      as much lift as possible. A navigational strategy was determined solely from the
      glider's pooled experiences, collected over several days in the field. The
      strategy relies on on-board methods to accurately estimate the local vertical
      wind accelerations and the roll-wise torques on the glider, which serve as
      navigational cues. We establish the validity of our learned flight policy through
      field experiments, numerical simulations and estimates of the noise in
      measurements caused by atmospheric turbulence. Our results highlight the role of
      vertical wind accelerations and roll-wise torques as effective mechanosensory
      cues for soaring birds and provide a navigational strategy that is directly
      applicable to the development of autonomous soaring vehicles.

PMID- 30232457
TI  - Transience of the North American High Plains landscape and its impact on surface
      water.
AB  - Ecosystem diversity and human activity in dry climates depend not just on the
      magnitude of rainfall, but also on the landscape's ability to retain water. This
      is illustrated dramatically in the High Plains of North America, where despite
      the semi-arid modern and past climate, the hydrologic conditions are diverse.
      Large rivers sourced in the Rocky Mountains cut through elevated plains that
      exhibit limited river drainage but widespread surface water in the form of
      ephemeral (seasonal) playa lakes1, as well as extensive groundwater hosted in the
      High Plains aquifer of the Ogallala formations2. Here we present a model, with
      supporting evidence, which shows that the High Plains landscape is currently in a
      transient state, in which the landscape has bifurcated into an older region with
      an inefficient river network and a younger, more efficient, river channel network
      that is progressively cannibalizing the older region. The older landscape
      represents the remnants of the Ogallala sediments that once covered the entirety
      of the High Plains, forming depositional fans that buried the pre-existing river
      network and effectively 'repaved' the High Plains3-6. Today we are witnessing the
      establishment of a new river network that is dissecting the landscape, capturing
      channels and eroding these sediment fans. Through quantitative analysis of the
      geometry of the river network, we show how network reorganization has resulted in
      a distinctive pattern of erosion, whereby the largest rivers have incised the
      older surface, removed fan heads near the Rocky Mountains and eroded the fan
      toes, but left portions of the central fan surface and the Ogallala sediments
      largely intact. These preserved fan surfaces have poor surface water drainage,
      and thus retain ephemeral water for wetlands and groundwater recharge. Our
      findings suggest that the surface hydrology and associated ecosystems are
      transient features on million-year timescales, and reflect the mode of landscape
      evolution.

PMID- 30232458
TI  - T cells in patients with narcolepsy target self-antigens of hypocretin neurons.
AB  - Narcolepsy is a chronic sleep disorder caused by the loss of neurons that produce
      hypocretin. The close association with HLA-DQB1*06:02, evidence for immune
      dysregulation and increased incidence upon influenza vaccination together suggest
      that this disorder has an autoimmune origin. However, there is little evidence of
      autoreactive lymphocytes in patients with narcolepsy. Here we used sensitive
      cellular screens and detected hypocretin-specific CD4+ T cells in all 19 patients
      that we tested; T cells specific for tribbles homologue 2-another self-antigen of
      hypocretin neurons-were found in 8 out of 13 patients. Autoreactive CD4+ T cells
      were polyclonal, targeted multiple epitopes, were restricted primarily by HLA-DR
      and did not cross-react with influenza antigens. Hypocretin-specific CD8+ T cells
      were also detected in the blood and cerebrospinal fluid of several patients with
      narcolepsy. Autoreactive clonotypes were serially detected in the blood of the
      same-and even of different-patients, but not in healthy control individuals.
      These findings solidify the autoimmune aetiology of narcolepsy and provide a
      basis for rapid diagnosis and treatment of this disease.

PMID- 30232460
TI  - Genetic and scRNA-seq Analysis Reveals Distinct Cell Populations that Contribute
      to Salivary Gland Development and Maintenance.
AB  - Stem and progenitor cells of the submandibular salivary gland (SMG) give rise to,
      maintain, and regenerate the multiple lineages of mature epithelial cells
      including those belonging to the ductal, acinar, basal and myoepithelial
      subtypes. Here we have exploited single cell RNA-sequencing and in vivo genetic
      lineage tracing technologies to generate a detailed map of the cell fate
      trajectories and branch points of the basal and myoepithelial cell populations of
      the mouse SMG during embryonic development and in adults. Our studies show that
      the transcription factor p63 and alpha-smooth muscle actin (SMA) serve as
      faithful markers of the basal and myoepithelial cell lineages, respectively and
      that both cell types are endowed with progenitor cell properties. However, p63+
      basal and SMA+ myoepithelial cells exhibit distinct cell fates by virtue of
      maintaining different cellular lineages during morphogenesis and in adults.
      Collectively, our results reveal the dynamic and complex nature of the diverse
      SMG cell populations and highlight the distinct differentiation potential of the
      p63 and SMA expressing subtypes in the stem and progenitor cell hierarchy. Long
      term these findings have profound implications towards a better understanding of
      the molecular mechanisms that dictate lineage commitment and differentiation
      programs during development and adult gland maintenance.

PMID- 30232459
TI  - Differentiation-state plasticity is a targetable resistance mechanism in basal
      like breast cancer.
AB  - Intratumoral heterogeneity in cancers arises from genomic instability and
      epigenomic plasticity and is associated with resistance to cytotoxic and targeted
      therapies. We show here that cell-state heterogeneity, defined by differentiation
      state marker expression, is high in triple-negative and basal-like breast cancer
      subtypes, and that drug tolerant persister (DTP) cell populations with altered
      marker expression emerge during treatment with a wide range of pathway-targeted
      therapeutic compounds. We show that MEK and PI3K/mTOR inhibitor-driven DTP states
      arise through distinct cell-state transitions rather than by Darwinian selection
      of preexisting subpopulations, and that these transitions involve dynamic
      remodeling of open chromatin architecture. Increased activity of many chromatin
      modifier enzymes, including BRD4, is observed in DTP cells. Co-treatment with the
      PI3K/mTOR inhibitor BEZ235 and the BET inhibitor JQ1 prevents changes to the open
      chromatin architecture, inhibits the acquisition of a DTP state, and results in
      robust cell death in vitro and xenograft regression in vivo.

PMID- 30232461
TI  - Salicylic acid in Populus tomentosa is a remote signalling molecule induced by
      Botryosphaeria dothidea infection.
AB  - The salicylic acid (SA) plays a critical role during the establishment of
      systemic acquired resistance (SAR) in uninfected plant tissues after localised
      exposure to a pathogen. Here, we studied SA in Populus tomentosa infected by the
      plant pathogen Botryosphaeria dothidea. The accumulation of SA and methyl
      salicylate (MeSA) occurred in chronological order in P. tomentosa. The SA and
      MeSA contents were greater at infected than uninfected sites. Additionally, a
      gene expression analysis indicated that SA might be accumulated by phenylalanine
      ammonialyase (PAL) and converted to MeSA by SA carboxyl methyltransferase (SAMT),
      while MeSA might convert to SA by SA-binding protein 2 (SABP2). The expressions
      of SAMT at infected sites and SABP2 at uninfected sites, respectively, were
      significantly up-regulated. Thus, SA might be converted to MeSA at infected sites
      and transported as a signalling molecule to uninfected sites, where it is
      converted to SA for SAR. Moreover, the expressions of pathogenesis-related genes
      PR-1, PR-2 and PR-5 in P. tomentosa were up-regulated by the B. dothidea
      infection. Our study determined that variations in SA and MeSA contents occur at
      infected and uninfected sites in poplar after pathogen infection and contributed
      to the remote signals for poplar SAR.

PMID- 30232462
TI  - The human gut pan-microbiome presents a compositional core formed by discrete
      phylogenetic units.
AB  - The complex community of microbes living in the human gut plays an important role
      in host wellbeing. However, defining a 'healthy' gut microbiome in terms of
      composition has remained an elusive task, despite its anticipated medical and
      scientific importance. In this regard, a central question has been if there is a
      'core' microbiome consisting of bacterial groups common to all healthy humans.
      Recent studies have been able to define a compositional core in human gut
      microbiome datasets in terms of taxonomic assignments. However, the description
      of the core microbiome in terms of taxonomic assignments may not be adequate when
      considering subsequent analyses and applications. Through the implementation of a
      dynamic clustering approach in the meta-analyisis of comprehensive 16S rRNA
      marker gene datasets, this study found that the human gut pan-microbiome presents
      a preeminent compositional core comprised of discrete units of varying
      phylogenetic depth present in all individuals studied. Since both microbial
      traits and ecological coherence show signs of phylogenetic conservation, this
      outcome provides a new conceptual framework in the study of the ecosystem, as
      well as important practical considerations which should be taken into account in
      future research.

PMID- 30232463
TI  - Correction: Mutant JAK3 phosphoproteomic profiling predicts synergism between
      JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute
      lymphoblastic leukemia.
AB  - Following the publication of this article the authors noted that data describing
      precisely where phosphorylation sites in proteins modulated following JAK1 or
      JAK3 inhibition in mutant T-ALL samples was not clearly annotated. Therefore an
      additional sheet has been added to Supplementary Table 2.

PMID- 30232464
TI  - Correction: Myeloproliferative leukemia protein activation directly induces
      fibrocyte differentiation to cause myelofibrosis.
AB  - Owing to the insufficient specificity of the anti-myeloproliferative leukemia
      protein (MPL) antibody in the original version of this Article, Figure 6 and
      parts of Figures 2a, 4e, and 5a do not represent the correct information. The
      corrected version of Figure 6 is in this correction and those of Figures 2a, 4e,
      and 5a are shown in the supplemental information.

PMID- 30232465
TI  - Deep-Ultraviolet Photodetectors Based on Epitaxial ZnGa2O4 Thin Films.
AB  - A single-crystalline ZnGa2O4 epilayer was successfully grown on c-plane (0001)
      sapphire substrate by metal-organic chemical vapor deposition. This epilayer was
      used as a ternary oxide semiconductor for application in high-performance metal
      semiconductor-metal photoconductive deep-ultraviolet (DUV) photodetectors (PDs).
      At a bias of 5 V, the annealed ZnGa2O4 PDs showed better performance with a
      considerably low dark current of 1 pA, a responsivity of 86.3 A/W, cut-off
      wavelength of 280 nm, and a high DUV-to-visible discrimination ratio of
      approximately 107 upon exposure to 230 nm DUV illumination than that of as-grown
      ZnGa2O4 PDs. The as-grown PDs presented a dark current of 0.5 mA, a responsivity
      of 2782 A/W at 230 nm, and a photo-to-dark current contrast ratio of
      approximately one order. The rise time of annealed PDs was 0.5 s, and the
      relatively quick decay time was 0.7 s. The present results demonstrate that
      annealing process can reduce the oxygen vacancy defects and be potentially
      applied in ZnGa2O4 film-based DUV PD devices, which have been rarely reported in
      previous studies.

PMID- 30232467
TI  - Alcohol intake and risk of erectile dysfunction: a dose-response meta-analysis of
      observational studies.
AB  - The purpose of the present study was to conduct a meta-analysis of cross
      sectional studies assessing the relationship between alcohol consumption and the
      risk of erectile dysfunction (ED). To identify relevant studies, databases such
      as Pubmed, Medline, Embase, and the Cochrane Library were searched from the
      inception of the present study to March 2016. Finally, 24 studies (154,295
      patients) were included. We combined a study-specific odds ratio (OR) estimated
      by using a random effects meta-analysis. The results of our meta-analysis
      indicated that light to moderate alcohol consumption (<21 drinks/week) was
      correlated with a decreased risk of erectile dysfunction (OR = 0.71; 95% CI: 0.59
      0.86; P = 0.000). However, regular (ever vs. never) and high alcohol consumption
      (>21 drinks/week) had no significant influence on the prevalence of ED (regular:
      OR = 0.87; 95% CI: 0.75-1.07; P = 0.062; high: OR = 0.99; 95% CI: 0.80-1.22; P =
      0.893). In a dose-response meta-analysis, a non-linear relationship was observed
      between alcohol consumption and risk of ED (P for non-linearity = 0.0000). In
      conclusion, moderate intake of alcohol exhibited a beneficial effect on the risk
      of ED, whereas regular and high consumption did not.

PMID- 30232466
TI  - Spinosad resistance affects biological parameters of Musca domestica Linnaeus.
AB  - Musca domestica is one of the major cosmopolitan insect pests of public health
      importance. Spinosad is considered an eco-friendly insecticide used for the
      management of M. domestica and other pests of significant concern. Cases of
      resistance against spinosad in M. domestica have been reported from some parts of
      the world; however, there are no reports of any negative effects of spinosad
      resistance on the fitness/biological parameters of M. domestica. To investigate
      fitness costs, a near isogenic M. domestica resistant strain (Spin-R) was
      constructed using Spin-UNSEL-susceptible and Spin-SEL-resistant strains sharing a
      close genetic background. We found significantly reduced rates of adult eclosion,
      fecundity, egg hatching, survival, and lengthened developmental time in the Spin
      R strain. Moreover, the values of different fitness parameters like biotic
      potential, mean relative growth rate, intrinsic rate of natural increase, and net
      reproductive rate, were also significantly reduced in the Spin-R strain, which
      reflect fitness costs most probably linked with spinosad resistance. The presence
      of fitness costs suggests likely instability of resistance to spinosad in M.
      domestica, which can be reverted by relaxing spinosad selection pressure and
      rotation with alternate insecticides. The wise use of insecticides will
      ultimately help to manage resistance in this pest and minimize environmental
      pollution.

PMID- 30232468
TI  - Roles of the RANKL-RANK axis in antitumour immunity - implications for therapy.
AB  - Recognizing that the transformative effects of immunotherapy are currently
      limited to a minority of patients with cancer, research efforts are increasingly
      focused on expanding and enhancing clinical responses by combining
      immunotherapies; the repurposing of existing drugs is an attractive approach,
      given their well-characterized safety and pharmacokinetic profiles. Receptor
      activator of nuclear factor-kappaB (RANK) and the RANK ligand (RANKL) were
      initially described in the context of T cell-dendritic cell interactions;
      however, the discovery of an obligate role of RANK signalling in
      osteoclastogenesis led to the development of the anti-RANKL antibody denosumab
      for antiresorptive indications, including bone metastases. Randomized clinical
      trials and post-marketing surveillance studies have established the acceptable
      safety profile of denosumab. More recently, several case reports involving
      patients with advanced-stage melanoma have described remarkable responses
      following concurrent treatment with denosumab and immune-checkpoint inhibitors.
      Randomized trials assessing similar combinations in patients with melanoma or
      renal cell carcinoma are now underway. Herein, we discuss the hallmark clinical
      trials of denosumab in light of possible immunological effects of this agent. We
      highlight the role of immune cells as sources of RANK and RANKL in the tumour
      microenvironment and review data on RANKL inhibition in mouse models of cancer.
      Finally, we describe hypothetical immune-related mechanisms of action, which
      could be assessed in clinical trials of immune-checkpoint inhibitors and
      denosumab in patients with cancer.

PMID- 30232469
TI  - Interaction of mitochondrial fission factor with dynamin related protein 1
      governs physiological mitochondrial function in vivo.
AB  - Mitochondria form a dynamic network governed by a balance between opposing
      fission and fusion processes. Because excessive mitochondrial fission correlates
      with numerous pathologies, including neurodegeneration, the mechanism governing
      fission has become an attractive therapeutic strategy. However, targeting fission
      is a double-edged sword as physiological fission is necessary for mitochondrial
      function. Fission is trigged by Drp1 anchoring to adaptors tethered to the outer
      mitochondrial membrane. We designed peptide P259 that distinguishes physiological
      from pathological fission by specifically inhibiting Drp1's interaction with the
      Mff adaptor. Treatment of cells with P259 elongated mitochondria and disrupted
      mitochondrial function and motility. Sustained in vivo treatment caused a decline
      in ATP levels and altered mitochondrial structure in the brain, resulting in
      behavioral deficits in wild-type mice and a shorter lifespan in a mouse model of
      Huntington's disease. Therefore, the Mff-Drp1 interaction is critical for
      physiological mitochondrial fission, motility, and function in vitro and in vivo.
      Tools, such as P259, that differentiate physiological from pathological fission
      will enable the examination of context-dependent roles of Drp1 and the
      suitability of mitochondrial fission as a target for drug development.

PMID- 30232471
TI  - A semiconducting metal-chalcogenide-organic framework with square-planar tetra
      coordinated sulfur.
AB  - We demonstrated here a novel semiconducting metal-chalcogenide-organic framework
      (MCOF-89) with an optical bandgap through the unlikely assembly between a metal
      chalcogenide unit and carboxylic acid. The elusive metal-chalcogenide unit
      [Mn4(MU4-S)] with square-planar tetra-coordinated sulfur (sptS) is for the first
      time observed in MOFs.

PMID- 30232470
TI  - The extraction of natural scene gist in visual crowding.
AB  - The gist of natural scenes can be extracted very rapidly and even without focal
      attention. However, it is unclear whether and to what extent the gist of natural
      scenes can break through the bottleneck of crowding, a phenomenon in which object
      recognition will be immensely impaired. In the first two experiments, a target
      scene, either presented alone or surrounded by four flankers, was categorized at
      basic (Experiment 1) or global levels (Experiment 2). It was showed that the
      elimination of high-level semantic information of flankers greatly alleviated the
      crowding effect, demonstrating that high-level information played an important
      role in crowding of scene gist. More importantly, participants were able to
      categorize the scenes in crowding at rather high accuracies, suggesting that the
      extraction of scene gist might be a prioritized process. To test this hypothesis,
      in Experiment 3 we compared the crowding effect of three types of stimuli,
      namely, scenes, facial expressions and letter "E"s. The results showed that
      scenes could be better categorized than the other two types of stimuli in the
      crowding condition. This scene gist advantage thus supported our hypothesis.
      Together, the present studies suggest that scene gist is highly recognizable in
      crowding, probably due to its prioritization in visual processing.

PMID- 30232472
TI  - Visualization of mitochondrial DNA in living cells with super-resolution
      microscopy using thiophene-based terpyridine Zn(ii) complexes.
AB  - We present a thiophene-based terpyridine Zn(ii) complex (namely LC) which could
      specifically target live cell mitochondria via binding with mitochondrial DNA
      (mtDNA). Due to its high biocompatibility, red emission and photo-stability,
      mtDNA distribution within mitochondrial cristae and inner matrix in living cells
      was successfully visualized using stimulated emission depletion (STED) nanoscopy
      with unprecedented resolution.

PMID- 30232478
TI  - Templated synthesis of spherical RNA nanoparticles with gene silencing activity.
AB  - RNA has inherent therapeutic and structural properties that make it an important
      component of biologically-functional nanoparticles. Using DNA-amphiphiles as
      synthetic templates, we report the synthesis of two classes of RNA-amphiphiles
      that self-assemble into spherical nanoparticles in aqueous solution and show gene
      silencing activity.

PMID- 30232479
TI  - Diastereoselective synthesis of 1,3-disubstituted isoindolines and sultams via
      bronsted acid catalysis.
AB  - The bis(trifluoromethane)sulfonimide (Tf2NH) catalyzed intramolecular
      hydroamidation of terminal alkynes is reported. The combination of Et3SiH and
      Tf2NH provides cis-1,3-disubstituted isoindolines and sultams in high yield (up
      to 98%) and high diastereoselectivity (up to 99 : 1 d.r.).

PMID- 30232480
TI  - Portable combination of Fourier transform infrared spectroscopy and differential
      mobility spectrometry for advanced vapor phase analysis.
AB  - Designing mobile devices for the analysis of complex sample mixtures containing a
      variety of analytes at different concentrations across a large dynamic range
      remains a challenging task in many analytical scenarios. To meet this challenge,
      a compact hybrid analytical platform has been developed combining Fourier
      transform infrared spectroscopy based on substrate-integrated hollow waveguides
      (iHWG-FTIR) with gas chromatography coupled differential mobility spectrometry
      (GC-DMS). Due to the complementarity of these techniques regarding analyte type
      and concentration, their combination provides a promising tool for the detection
      of complex samples containing a broad range of molecules at different
      concentrations. To date, the combination of infrared spectroscopy and ion
      mobility techniques remains expensive and bound to a laboratory utilizing e.g.
      IMS as prefilter or IR as ionization source. In the present study, a cost
      efficient and portable solution has been developed and characterized representing
      the first truly hyphenated IR-DMS system. As a model analyte mixture, 5 ppm
      isopropylmercaptan (IPM) in methane (CH4) were diluted, and the concentration
      dependent DMS signal of IPM along with the concentration-dependent IR signal of
      CH4 were recorded for all three hybrid IR-DMS systems. While guiding the sample
      through the iHWG-FTIR or the GC-DMS first did not affect the obtained signals,
      optimizing the IR data acquisition parameters did benefit the analytical results.

PMID- 30232481
TI  - BSA-bioinspired gold nanorods loaded with immunoadjuvant for the treatment of
      melanoma by combined photothermal therapy and immunotherapy.
AB  - The development of therapeutic methods that can effectively delay tumor growth,
      inhibit tumor metastases, and protect the host from tumor recurrence still faces
      challenges. Nanoparticle-based combination therapy may provide an effective
      therapeutic strategy. Herein, we show that bovine serum albumin (BSA)-bioinspired
      gold nanorods (GNRs) were loaded with an immunoadjuvant for combined photothermal
      therapy (PTT) and immunotherapy for the treatment of melanoma. In this work,
      cetyltrimethylammonium bromide (CTAB)-coated GNRs were successively decorated
      with polyethylene glycol (PEG) and BSA, and loaded with an immunoadjuvant
      imiquimod (R837). The synthesized mPEG-GNRs@BSA/R837 nanocomplexes under near
      infrared (NIR) irradiation could effectively kill tumors and trigger strong
      immune responses in treating metastatic melanoma in mice. Furthermore, the
      nanocomplex-based PTT prevented lung metastasis and induced a strong long-term
      antitumor immunity to protect the treated mice from tumor recurrence. The
      nanocomplex-based PTT in combination with immunotherapy may be potentially
      employed as an effective strategy for the treatment of melanoma and other
      metastatic cancers.

PMID- 30232482
TI  - Controllable drug release from nano-layered hollow carrier by non-human enzyme.
AB  - Natural polymers are widely used in biomedical applications because of their
      numerous effects. Especially, plant-derived natural polymers extracted from cell
      walls, especially wood, which is abundant, inexpensive and nontoxic to cells,
      have high mechanical strength to retain their turgor pressure. Plant-derived
      polymers are also unaffected by enzymes present in the human body, having a
      strong possibility to create a polymeric structure that releases drugs only
      exactly where needed. Therefore, plant-derived polymers are suitable for use in
      drug delivery systems (DDS) as they have durability with few drug leakage issues
      in the body. Here, to improve drug incorporation and release efficiency, we
      prepared a multilayer nanofilm from tannic acid (TA) and lignin extracted from
      plants and wood. We used a strategy involving film degradation by tannase and
      laccase, which are not present in humans, to depolymerize TA and lignin,
      respectively. The TA and lignin film was highly stable for 7 days at pH 3-7 and
      was readily degraded after enzyme treatment. We also observed controllable drug
      release and anticancer effect from the TA and lignin hollow carriers depending on
      enzymatic activity. By taking advantage of plant-derived polymers and non-toxic
      enzymatic reactions, we have demonstrated the film growth and degradation
      mechanism in depth and explored their use in a smart DDS with easily controlled
      release kinetics, which is useful as a DDS platform.

PMID- 30232483
TI  - Anion-encapsulating fullerenes behave as large anions: a DFT study.
AB  - M06L/6-311++G(d,p)//M06L/6-31G(d,p) level density functional theory studies show
      that the endohedral reaction of C60 with X- (X = F, Cl, Br, OH, NH2, NO2, CN, and
      ClO) is exothermic by 37.8-65.2 kcal mol-1. The exothermic character of the
      reaction is drastically reduced in polar and nonpolar solvents due to the lack of
      direct solvation influence on the encapsulated anion. In all X-@C60, the occupied
      frontier molecular orbitals (FMOs) are located on X- while the energy levels of
      FMOs centered on C60 are very similar to those of the C60- radical anion.
      Molecular electrostatic potential (MESP) analysis of X-@C60 revealed that the
      negative character of the MESP minimum (Vmin) on the carbon cage increases by ~72
      fold compared to C60, which is very similar to the enhancement in the negative
      MESP observed on the C60- radical anion. The MESP data and quantum theory of
      atoms in molecules (QTAIM) analysis of charge, electron delocalization index, and
      Laplacian of bond critical point (bcp) support significant electron sharing from
      the anion to the carbon atoms of the fullerene cage, which makes the cage behave
      like a very large anion in a closed shell configuration. The data are also
      supportive of a multicenter charge-shift type of bonding interaction between the
      anion and the carbon cage. The anionic nature of the fullerene cage has been
      verified in the cases of larger systems such as Cl-@C70, Cl-@C84, and Cl-@C90.
      The binding of a counter cation K+ with X-@C60 is found to be highly exothermic
      (~72 kcal mol-1) and very similar to the binding of K+ with the C60- radical
      anion (72.9 kcal mol-1), which suggests that C60 in X-@C60 behaves as a closed
      shell anion.

PMID- 30232486
TI  - Efficient synthesis of tetrazole hemiaminal silyl ethers via three-component
      hemiaminal silylation.
AB  - An efficient route to construct 2,5-disubstituted tetrazole hemiaminal silyl
      ethers via one-pot three-component hemiaminal silylation of 5-substituted
      tetrazoles, aldehydes, and silyl triflates was developed. Diverse 2,5
      disubstituted tetrazole hemiaminal silyl ethers were obtained with 37 : 63->99 :
      1 regioisomeric ratios. The regioselectivities of this reaction were
      significantly affected by steric hindrance and the conjugation effects of
      substitutions on the 5-position of tetrazoles.

PMID- 30232484
TI  - Entropy drives the insertion of ibuprofen into model membranes.
AB  - Understanding the migration of exogenous molecules to the interior of cell
      membranes is of pivotal importance to the design of new drugs and to the
      improvement of the capabilities of existing ones. This research dissects, from a
      molecular perspective, using classical molecular dynamics, the thermodynamic
      factors driving the insertion of ibuprofen into a model phosphatidylcholine
      membrane in an aqueous environment. We suggest an analysis of the insertion path
      that focuses on the net resulting force acting on the tertiary
      drug/water/membrane system; this allows us to understand the opposition that
      ibuprofen has to overcome as it inserts into the membrane. We provide conclusive
      evidence that entropy changes, arising from an increase of the number of possible
      microstates due to structural reorganization of the tertiary system, are the main
      factor driving this process. Our results allow us to unambiguously rationalize
      long standing conflicting experimental reports not understood up to now.

PMID- 30232489
TI  - Dynamical insights into the mechanism of a droplet detachment from a fiber.
AB  - Quantifying the detachment behavior of a droplet from a fiber is important in
      many applications such as fog harvesting, oil-water separation, or water
      management in fuel cells. When the droplets are forcibly removed from hydrophilic
      fibers, the ease of detachment strongly depends on droplet volume and the rate of
      the process controlled by the applied force. Experiments, conducted on a
      ferrofluid under magnetic force, as well as continuum level calculations from
      fluid mechanics have so far been unable to resolve the time-dependent dynamics of
      droplet detachment and, most importantly, to assess the role of the applied force
      as the key determinant of the volume of the droplet residue remaining on the
      fiber after detachment. In the present work, we study the mechanism of water
      droplet detachment and retention of residual water on smooth hydrophilic fibers
      using nonequilibrium molecular dynamics simulations. We investigate how the
      applied force affects the breakup of a droplet and how the minimal detaching
      force per unit mass decreases with droplet size. We extract scaling relations
      that allow extrapolation of our findings to larger length scales that are not
      directly accessible by molecular models. We find that the volume of the residue
      on a fiber varies nonmonotonically with the detaching force, reaching the maximal
      size at an intermediate force and associated detachment time. The strength of
      this force decreases with the size of the drop, while the maximal residue
      increases with the droplet volume, V, sub-linearly, in proportion to the V2/3.

PMID- 30232490
TI  - Correction: Transition path time distribution and the transition path free energy
      barrier.
AB  - Correction for 'Transition path time distribution and the transition path free
      energy barrier' by Eli Pollak et al., Phys. Chem. Chem. Phys., 2016, 18, 28872
      28882.

PMID- 30232491
TI  - Preparation of the Ru3(CO)8-pyridine-alcohol cluster and its use for the
      selective catalytic transformation of primary to secondary amines.
AB  - The synthesis of pyridine alcohol based ruthenium carbonyl clusters
      Ru3(hep)2(CO)8 (1), Ru3(hpp)2(CO)8 (2), and Ru3(bhmp-H)2(CO)8 (3) {hep-H = 2-(2
      hydroxyethyl)pyridine, hpp-H = 2-(3-hydroxypropyl)pyridine and bhmp-H2 = 2,6
      bis(hydroxymethyl)pyridine} has been carried out by the reaction of the
      corresponding pyridine-alcohol ligands with Ru3(CO)12. Clusters 1-3 have been
      characterized using elemental analysis, NMR, FT-IR, mass spectrometry and single
      crystal X-ray structures. The clusters were explored for the selective catalytic
      transformation of primary amines into secondary amines using alcohols as the mono
      alkylating agents via hydrogen transfer reactions. All three display efficient
      catalytic activity with 1 being the most effective.

PMID- 30232494
TI  - Fluctuations near the liquid-liquid transition in a model of silica.
AB  - We perform large-scale molecular dynamics (MD) simulations of systems with up to
      216 000 atoms to study the low-temperature behavior of the mWAC model of silica.
      Recent studies show that mWAC exhibits a liquid-liquid phase transition (LLPT),
      similar to the one hypothesized to occur in deeply supercooled water.
      Characterization of mWAC's small-angle scattering behavior reveals an anomalous
      increase in fluctuations in density and local tetrahedral order in the liquid
      upon cooling. Moreover, the static correlation length computed from the anomalous
      scattering component exhibits power-law growth as temperature decreases and
      appears to diverge near 3300 K. These observations are consistent with previous
      studies indicating the existence of a liquid-liquid critical point near this
      temperature. Finally, we use MD to thermally quench systems ranging from 4500 to
      432 000 atoms in size into the predicted region of liquid-liquid coexistence.
      Spontaneous liquid-liquid separation is observed in each system following the
      quench, demonstrating that this behavior is not strongly influenced by finite
      size effects. These findings parallel those recently reported for the ST2 model
      of water near its LLPT, suggesting common signatures that may be useful for
      identifying similar transitions in other systems.

PMID- 30232493
TI  - Magnolol dimer-derived fragments as PPARgamma-selective probes.
AB  - Partial agonists of the transcription factor PPARgamma (peroxisome proliferator
      activated receptor gamma) have shown potential for the treatment of metabolic and
      inflammatory conditions and novel activators serve as valuable tool and lead
      compounds. Based on the natural product magnolol (I) and recent structural
      information of the ligand-target interaction we have previously developed
      magnolol dimer (II) which has been shown to have enhanced affinity towards
      PPARgamma and improved selectivity over RXRalpha (retinoid X receptor alpha),
      PPARgamma's heterodimerization partner. In this contribution we report the
      synthesis and evaluation of three fragments of the dimeric lead compound by
      structural simplifications. Sesqui magnolol A and B (III and IV) were found to
      exhibit comparable activities to magnolol dimer (II) and selectivity over
      RXRalpha persisted. Computational studies suggest a common pharmacophore of the
      distinctive biphenyl motifs. Truncated magnolol dimer (V) on the other hand does
      not share this feature and was found to act as an antagonist.

PMID- 30232496
TI  - Hybrid DFT investigation of the energetics of Mg ion diffusion in alpha-MoO3.
AB  - Rechargeable batteries that utilize divalent Mg ions as the charge carrier
      species can in principle achieve substantially greater volumetric energy
      densities than conventional Li-ion batteries. One significant impediment to the
      development of commercially viable Mg-ion batteries is the slow rate of Mg ion
      diffusion through otherwise promising cathode materials. Accurate prediction of
      the activation energies associated with this diffusion process using density
      functional theory (DFT) is especially challenging due to self-interaction errors
      intrinsic to DFT that lead to over-delocalization of the d-electrons. One
      effective but highly computationally demanding approach to reducing self
      interaction errors is the use of hybrid functionals, which incorporate a fraction
      of exact Hartree-Fock exchange. In this work, we assess the effects of exact
      exchange on computed activation energies for ion diffusion in one potential
      cathode material, alpha-MoO3. In contrast to previous studies that primarily
      utilize non-hybrid functionals, we perform nudged elastic band calculations in
      which the nuclear coordinates are fully converged using both hybrid functionals
      and k-point sampling. It is found that while non-hybrid functionals indicate the
      existence of thermodynamically accessible channels for bulk Mg ion diffusion in
      all three dimensions, hybrid functionals predict that some of these channels are
      largely inaccessible under typical charge/discharge conditions. Furthermore, it
      is demonstrated that certain commonly used approximations for incorporating the
      effects of Hartree-Fock exchange are inadequate for this system, including DFT+U
      calculations and the use of single-point hybrid calculations using atomic
      positions obtained using non-hybrid functionals.

PMID- 30232497
TI  - Nd3+,Ho3+-Codoped apatite-related NaLa9(GeO4)6O2 phosphors for the near- and
      middle-infrared region.
AB  - The apatite-like NaLa9(GeO4)6O2:Nd3+,Ho3+ phosphor is prepared using the solid
      state method. Rietveld refinement of high-resolution time-of-flight neutron
      powder diffraction measurements indicate that this compound crystallizes in the
      hexagonal system with space group P63/m, Z = 1 and unit cell parameters a =
      9.88903(6) A, c = 7.25602(5) A, V = 614.521(7) A3 at room temperature. The 4f
      sites are statistically occupied by La, Nd and Na, while 6h sites are occupied by
      La and Nd. Luminescence in the near- and middle-IR range caused by the
      transitions in neodymium and holmium ions is excited under 808 nm laser diode
      radiation. The highest emission intensity in NaLa9-x-yNdxHoy(GeO4)6O2 is attained
      at trace amounts of holmium, and it decreases sharply when y increases to 0.01.
      The IR phosphors have a good thermal stability and exhibit a very weak
      upconversion emission in the red spectral range upon 808 nm excitation. A scheme
      of excitation and emission pathways involving ground/excited state absorption,
      energy transfer, cross-relaxation, nonradiative multiphonon relaxation processes
      in Nd3+ and Ho3+ ions has been proposed. The data analysis indicates that Nd3+
      ions serve as sensitizers for Ho3+ ions in these compounds, stimulating intense
      2.1 MUm and 2.7 MUm emissions. These apatite-related germanate phosphors are
      promising materials for near- and middle-infrared solid-state lighting
      applications.

PMID- 30232498
TI  - Preparation of oxazolines and oxazoles via a PhI(OAc)2-promoted cyclization of N
      propargylamides.
AB  - A metal-free cyclization of N-propargylamides for the synthesis of various
      oxazolines and oxazoles via a 5-exo-dig process is presented. Using
      (diacetoxyiodo)benzene (PIDA) as a reaction promoter and lithium iodide (LiI) as
      an iodine source, intramolecular iodooxygenation of N-propargylamides proceeded
      readily, leading to the corresponding (E)-5-iodomethylene-2-oxazolines in good to
      excellent isolated yields. In addition, using the PhI(OAc)2/LiI system, N
      propargylamides can be converted to the corresponding oxazole-5-carbaldehydes in
      the presence of oxygen under visible light irradiation. The resulting products
      can be further converted into various oxazoline and oxazole derivatives after
      simple derivatizations, and this method ultimately offers an efficient route to a
      variety of biologically active structures.

PMID- 30232500
TI  - Erratum to: Anatomic stabilization of chronic lateral instability of the ankle :
      Gold technique.
AB  - Erratum to: Oper Orthop Traumatol 2017 https://doi.org/10.1007/s00064-017-0513-9
      The article was wrongly published under the article type "Review". Please note
      that the article is an "Original Paper".The publisher apologizes to the authors
      and ....

PMID- 30232499
TI  - Resource allocation optimization with multi-trait genomic prediction for bread
      wheat (Triticum aestivum L.) baking quality.
AB  - KEY MESSAGE: Multi-trait genomic prediction models are useful to allocate
      available resources in breeding programs by targeted phenotyping of correlated
      traits when predicting expensive and labor-intensive quality parameters. Multi
      trait genomic prediction models can be used to predict labor-intensive or
      expensive correlated traits where phenotyping depth of correlated traits could be
      larger than phenotyping depth of targeted traits, reducing resources and
      improving prediction accuracy. This is particularly important in the context of
      allocating phenotyping resource in plant breeding programs. The objective of this
      work was to evaluate multi-trait models predictive ability with different depth
      of phenotypic information from correlated traits. We evaluated 495 wheat advanced
      breeding lines for eight baking quality traits which were genotyped with
      genotyping-by-sequencing. Through different approaches for cross-validation, we
      evaluated the predictive ability of a single-trait model and a multi-trait model.
      Moreover, we evaluated different sizes of the training population (from 50 to 396
      individuals) for the trait of interest, different depth of phenotypic information
      for correlated traits (50 and 100%) and the number of correlated traits to be
      used (one to three). There was no loss in the predictive ability by reducing the
      training population up to a 30% (149 individuals) when using correlated traits. A
      multi-trait model with one highly correlated trait phenotyped for both the
      training and testing sets was the best model considering phenotyping resources
      and the gain in predictive ability. The inclusion of correlated traits in the
      training and testing lines is a strategic approach to replace phenotyping of
      labor-intensive and high cost traits in a breeding program.

PMID- 30232501
TI  - [Revascularization of visceral arteries: is less more?]

PMID- 30232502
TI  - [Distal radius fractures : Current treatment concepts and controversies].
AB  - Distal radius fractures represent the most frequent bone fractures in humans.
      Although the treatment was dominated for decades by conservative measures or
      closed surgical procedures, such as percutaneous wire osteosynthesis, a paradigm
      shift was instigated by the introduction and rapid dissemination of volar locking
      plate osteosynthesis (VLP). The novel procedure was soon proclaimed to be the
      gold standard and applied for practically all forms of fractures of the distal
      radius. In addition to clinical mishaps, e.g. failure to address dorsal edge
      fragments or the occurrence of extensor and flexor tendon irritation, the
      publication of various prospective randomized studies and meta-analyses led to a
      certain degree of disillusionment. In comparison to percutaneous wire
      osteosynthesis, no differences in the clinical result could be established for
      VLP 1 year postoperatively. It was therefore obvious that not all problems of the
      distal radius could be solved using the innovative instrument of volar locking
      plates. This article gives an overview on the current insights and reflects the
      current expert opinion on the present concepts for the treatment of distal radius
      fractures. This is illustrated by comprehensive case presentations.

PMID- 30232503
TI  - [The ulm emergency algorithm for the acute treatment of drug-induced, bradykinin
      mediated angioedema].
AB  - BACKGROUND: Bradykinin-mediated, drug-induced edema like ACE-inhibitor-induced
      angioedema (ACEi AE) is almost exclusively located in the head and neck region
      and is potentially life threatening. To date, there are no guidelines or
      officially-approved treatments available for this pathology. OBJECTIVES: We
      sought to provide a structured therapeutic algorithm for the acute treatment of
      drug-induced bradykinin-mediated angioedema. MATERIALS AND METHODS: We analyzed
      data (especially the course of disease and therapy) of all patients with acute
      angioedema, who presented to the Department of Otorhinolaryngology, Head and Neck
      Surgery at the University of Ulm (2010-2015). We also conducted a literature
      review on PubMed with the terms "acute angioedema", "angioedema emergency", "ACE
      angioedema", "bradykinin angioedema" and "angioedema therapy". Other fundamental
      references were the recent German guidelines "hereditary angioedema",
      "anaphylaxis" and "airway management". RESULTS: An emergency algorithm was
      generated as a flowchart for the acute therapy of bradykinin-mediated drug
      induced angioedema was generated. We focused on the decision criteria for
      intubation/airway management and pharmacological therapy: antihistamines and
      glucocorticoids versus anti-bradykinin treatment. Furthermore, recommendations
      for inpatient monitoring have been derived. CONCLUSION/DISCUSSION: To date,
      therapy of drug-induced bradykinin-mediated angioedema is performed according to
      an "off-label" use and without officially-approved guidelines. The presented
      emergency algorithm provides a first approach for a structured therapeutic
      concept for a potentially life-threatening pathology.

PMID- 30232506
TI  - Post-auricular lump: CT diagnosis.

PMID- 30232505
TI  - Facial growth direction after surgical intervention to relieve mouth breathing: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: A systematic review was performed to assess the prognosis for facial
      growth direction documented by mandibular plane inclination and anterior face
      height in growing subjects who had undergone surgical intervention to relieve
      mouth breathing (PROSPERO database, registration no. CRD 42013005707). METHODS:
      PubMed, Scopus, Web of Science, the Cochrane Library and LILACS were searched
      based on the guidelines of the PRISMA statement. Included were longitudinal
      studies with mouth-breathing patients who had undergone surgical interventions to
      relieve their respiratory pattern, with a minimum follow-up of one year. RESULTS:
      A total of 1555 studies were identified, whereby only three nonrandomized
      clinical trials comprising 155 participants met the inclusion criteria. Primary
      outcome was change between the initial and final measurements of the mandibular
      plane-SN angle (95% confidence interval [CI] -2.13 degrees  [-3.08, -1.18]).
      Secondary outcomes included changes in total anterior face height (AFH; 95% CI 
      0.76 mm [-1.91, 0.38]), upper AFH (95% CI 0.09 mm [-0.57, 0.74]), and lower AFH
      (95% CI 0.06 mm [-0.87, 0.99]). Risk of bias was low for most of bias domains and
      the quality of evidence across the studies was considered to be very low. The
      design, the small number of participants, and the absence of blinding generated
      imprecision. CONCLUSIONS: There is very low evidence that the mandibular growth
      direction became more horizontal during the first year after surgery to treat
      mouth breathing. The total anterior facial height decreased, although not always
      significantly.

PMID- 30232504
TI  - Transfer RNA-derived fragments and tRNA halves: biogenesis, biological functions
      and their roles in diseases.
AB  - The number of studies on non-coding RNAs has increased substantially in recent
      years owing to their importance in gene regulation. However, the biological
      functions of small RNAs from abundant species of housekeeping non-coding RNAs
      (rRNA, tRNA, etc.) remain a highly studied topic. tRNA-derived small RNAs
      (tsRNAs) refer to the specific cleavage of tRNAs by specific nucleases [e.g.,
      Dicer and angiogenin (ANG)] in particular cells or tissues or under certain
      conditions such as stress and hypoxia. tsRNAs are a type of non-coding small RNA
      that are widely found in the prokaryotic and eukaryotic transcriptomes and are
      generated from mature tRNAs or precursor tRNAs at different sites. There are two
      main types of tsRNAs, tRNA-derived fragments (tRFs) and tRNA halves. tRFs are 14
      30 nucleotides (nt) long and mainly consist of three subclasses: tRF-5, tRF-3,
      and tRF-1. tRNA halves, which are 31-40 nt long, are generated by specific
      cleavage in the anticodon loops of mature tRNAs. There are two types of tRNA
      halves, 5'-tRNA halves and 3'-tRNA halves. tsRNAs have multiple biological
      functions including acting as signaling molecules in stress responses and as
      regulators of gene expression. Additionally, they have been considered to be
      involved in RNA processing, cell proliferation, translation suppression, the
      modulation of DNA damage response, and neurodegeneration. More importantly, they
      are closely related to the occurrence of many human diseases such as tumors,
      infectious diseases, metabolic diseases, and neurological diseases. Moreover,
      tsRNAs have the potential to become new biomarkers for disease diagnosis.
      Continuous investigations will help us to understand their generation and
      regulatory mechanisms as well as the possible roles of tRFs and tRNA halves.

PMID- 30232507
TI  - Traumatic brain injury as an independent risk factor for problem gambling: a
      matched case-control study.
AB  - PURPOSE: To assess whether traumatic brain injury (TBI) increases the risks of
      subsequent problem gambling. METHODS: We conducted a matched case-control
      analysis of adults in Ontario, Canada. The study included those who self-reported
      their gambling activities in the Canadian Community Health Survey 2007-2008.
      Using Problem Gambling Severity Index, we defined cases as those who were problem
      gamblers and controls who were recreational gamblers. Cases were matched to
      controls 1:2 using propensity scores based on demographics, prior mental health,
      and self-reported behaviours. The main predictor was prior TBI defined as
      requiring emergency care and identified using ICD-10 codes from administrative
      health databases. We estimated the likelihood of prior TBI in problem gamblers
      compared to controls using conditional logistic regression. RESULTS: Of 30,652
      survey participants, 16,002 (53%) reported gambling activity of whom 14,910 (49%)
      were recreational gamblers and 4% (n = 1092) were problem gamblers. A total of
      1469 respondents (5%) had a prior TBI. Propensity score matching yielded 2038
      matched pairs with 1019 cases matched to 2037 controls. Case-control analysis
      showed a significant association between prior TBI and subsequent problem
      gambling (odds ratio 1.27, 95% confidence interval 1.07-1.51, P = 0.007). The
      increased risk was mostly apparent in men aged 35 to 64 years who reported
      alcohol use or smoking. The relative risk of problem gambling in those with two
      or more TBIs equated to an odds ratio of 2.04 (95% confidence interval 1.05
      3.99). CONCLUSIONS: We found that a prior TBI was associated with an increased
      subsequent risk of problem gambling. Our findings support more awareness,
      screening, and treating problem gambling risks among TBI patients.

PMID- 30232508
TI  - Kienbock's disease with non-negative ulnar variance : Treatment with combined
      radial wedge and shortening osteotomy.
AB  - PURPOSE: There are only few studies that focused on Kienbock's disease with non
      negative ulnar variance, even though many surgical procedures have been
      introduced. A combined radial wedge and shortening osteotomy was carried out for
      Kienbock's disease with non-negative ulnar variance. The purpose of this article
      is to report the results of this procedure by analyzing the clinical and
      radiological data. MATERIAL AND METHODS: The data for patients with Kienbock's
      disease who were treated by combined radial wedge and shortening osteotomy
      between 2007 and 2016 were retrospectively reviewed. A total of 18 patients (8
      males, 10 females), average age 37 years, were included in this study and the
      mean follow-up period was 22.3 months. Radiological analysis included Lichtman
      stage, ulnar variance, radial inclination, carpal height ratio, radioscaphoid
      angle and Stahl's index. Clinical analysis included range of motion (ROM), visual
      analog scale (VAS) score, grip power, modified Mayo wrist score (MMWS), and
      disabilities of arm, shoulder and hand (DASH) score. RESULTS: Preoperative
      radiological analysis showed 16 cases of Lichtman stage IIIA and 2 cases of stage
      IIIB. Preoperative ulnar variance was +0.51 mm, radial inclination was 27.7o,
      carpal height ratio was 0.49, radioscaphoid angle was 52.8o and Stahl's index was
      0.42. All patients had solid union at the osteotomy site. At the final follow-up
      the average ulnar variance was +1.9 mm, radial inclination was 16.5o, carpal
      height ratio was 0.48, radioscaphoid angle was 58.2o and Stahl's index was 0.36.
      Clinical analysis showed that the average dorsiflexion of the wrist was increased
      by 8.4o and palmar flexion of the wrist was increased by 29.6o. Grip power was
      increased by an average of 9.9 kg. Average VAS at the final follow-up was 1.0,
      DASH score was 4.3, and modified Mayo wrist score was 78.1. CONCLUSION: Radial
      wedge and shortening osteotomy can be recommended as an option for Kienbock's
      disease with non-negative ulnar variance, based on acceptable results from this
      study.

PMID- 30232511
TI  - Is There a Risk to Humans from Consuming Octopus Species from Sites with High
      Environmental Levels of Metals?
AB  - Although octopuses are in high-demand globally and can bioaccumulate high
      concentrations of metals, the risk associated to its consumption is poorly
      understood. We compiled literature data from eight locations in Europe, North
      America and Northern Africa with different environmental levels of metals to
      evaluate: (1) the risk to human health through consumption of muscle tissues and
      digestive glands of Octopus hubbsorum, O. vulgaris and Eledone cirrhosa, and (2)
      the maximum allowable consumption rates (CRlim). The assessments were done
      according the United States Environmental Protection Agency. The results indicate
      the absence of health risk through consumption of muscle tissues, and high health
      risk through consumption of digestive glands (attributed to its high Cd levels),
      reflected in its 1ow CRlim values. In conclusion, even in contaminated sites the
      consumption of octopus muscle tissues is not an issue of concern, while the
      consumption of digestive glands should be more carefully monitored to avoid
      health problems.

PMID- 30232509
TI  - Prognostic value of plasma MR-proADM vs NT-proBNP for heart failure in people
      with type 2 diabetes: the SURDIAGENE prospective study.
AB  - AIMS/HYPOTHESIS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is the
      gold standard prognostic biomarker for diagnosis and occurrence of heart failure.
      Here, we compared its prognostic value for the occurrence of congestive heart
      failure with that of plasma mid-region pro-adrenomedullin (MR-proADM), a
      surrogate for adrenomedullin, a vasoactive peptide with vasodilator and
      natriuretic properties, in people with type 2 diabetes. METHODS: Plasma MR-proADM
      concentration was measured in baseline samples of a hospital-based cohort of
      consecutively recruited participants with type 2 diabetes. Our primary endpoint
      was heart failure requiring hospitalisation. RESULTS: We included 1438
      participants (age 65 +/- 11 years; 604 women and 834 men). Hospitalisation for
      heart failure occurred during follow-up (median 64 months) in 206 participants;
      the incidence rate of heart failure was 2.5 (95% CI 2.2, 2.9) per 100 person
      years. Plasma concentrations of MR-proADM and NT-proBNP were significantly
      associated with heart failure in a Cox multivariable analysis model when adjusted
      for age, diabetes duration, history of coronary heart disease, proteinuria and
      baseline eGFR (adjHR [95%CI] 1.83 [1.51, 2.21] and 2.20 [1.86, 2.61],
      respectively, per 1 SD log10 increment, both p < 0.001). MR-proADM contributed
      significant supplementary information to the prognosis of heart failure when we
      considered the clinical risk factors (integrated discrimination improvement [IDI,
      mean +/- SEM] 0.021 +/- 0.007, p = 0.001) (Table 3). Inclusion of NT-proBNP in
      the multivariable model including MR-proADM contributed significant complementary
      information on prediction of heart failure (IDI [mean +/- SEM] 0.028 +/- 0.008, p
      < 0.001). By contrast, MR-proADM did not contribute supplementary information on
      prediction of heart failure in a model including NT-proBNP (IDI [mean +/- SEM]
      0.003 +/- 0.003, p = 0.27), with similar results for heart failure with reduced
      ejection fraction and preserved ejection fraction. CONCLUSIONS/INTERPRETATION: MR
      proADM is a prognostic biomarker for heart failure in people with type 2 diabetes
      but gives no significant complementary information on prediction of heart failure
      compared with NT-proBNP.

PMID- 30232510
TI  - Morphine as a treatment of cancer-induced pain-is it safe? A review of in vivo
      studies and mechanisms.
AB  - Morphine has been used in the treatment of pain for centuries. It is commonly
      used by oncology in terminal cancer cases and by surgery perioperatively for
      oncology surgery. Its extra-analgesic effects on cancer have been described
      extensively but conflicting results abound. It has been shown to have varying
      effects on tumour progression, cell proliferation, tumour invasion, angiogenesis,
      immune function, and metastatic potential. In vivo studies on the effects of
      morphine and the mu-opioid receptor on tumours are discussed below. Mechanisms
      involved are also discussed, drawn from a combination of both in vivo and in
      vitro methods. At present, no consensus can be drawn from data collected, and
      further studies are necessary to elicit the safest method and agent for analgesia
      in oncology patients.

PMID- 30232512
TI  - Effect of Rotary Evaporator Water Bath Temperature on Recovery Rate of Phthalate
      Esters.
AB  - To clarify the influence of water bath temperature on the decompression and
      concentration efficiency of a rotary evaporator, accurate control of the water
      bath temperature is required. Therefore, the water bath temperature control
      system of a rotary evaporator was studied using the recovery rate of phthalate
      esters (PAEs) as the indicator. The results showed that when the temperature of
      the rotary evaporator was set at 40 degrees C, the actual temperature range of
      the concentrated liquid would change from 26-41 to 39-41 degrees C. By modifying
      the water bath temperature control system, the recovery rate of PAEs could be
      increased from 72.4% to 85.6% to 93.2%-98.5%. This test indicates that
      temperature has a great influence on vacuum concentration, and the recovery rate
      of PAEs can be improved by modifying the water bath temperature control system
      used in the rotary evaporator.

PMID- 30232513
TI  - An Unusual Electrocardiogram.
AB  - A 56-year-old female was hospitalized and her admission ECG differed from
      previous tracings. Knowledge of variant cardiac anatomy along with awareness of
      common pitfalls in ECG recording reveals the clinical diagnosis and explains the
      difference.

PMID- 30232514
TI  - Immune biomarkers for predicting response to adoptive cell transfer as cancer
      treatment.
AB  - Adoptive cell transfer (ACT) is a form of personalised immunotherapy which has
      shown promising results in metastasised cancer. For this treatment, autologous T
      lymphocytes are selected and stimulated in vitro before re-administration in
      large numbers. However, only a fraction of patients benefit from ACT, and it is
      not yet known what biomarkers can predict treatment outcome. In this review, we
      describe what tumour characteristics are associated with response to ACT. Based
      on the current knowledge, the best candidate biomarker for a good anti-tumour
      response seems to be a large number of neoantigens with a homogeneous
      distribution across the tumour in combination with sufficient MHC-I expression
      level. Additionally, it is necessary to be able to isolate a diverse population
      of T cells reactive to these neoantigens from tumour tissue or peripheral blood.
      Additional promising candidate biomarkers shared with other cancer
      immunotherapies are a large number of tumour-infiltrating cytotoxic and memory T
      cells, normal levels of glycolysis, and a pro-inflammatory cytokine profile
      within the tumour. Intense research in this field will hopefully result in
      identification of more biomarkers for cancers with low mutational load.

PMID- 30232515
TI  - Left ventricular extracellular volume fraction and atrioventricular interaction
      in hypertension.
AB  - OBJECTIVES: Left atrial enlargement (LAE) predicts cardiovascular morbidity and
      mortality. Impaired LA function also confers poor prognosis. This study aimed to
      determine whether left ventricular (LV) interstitial fibrosis is associated with
      LAE and LA impairment in systemic hypertension. METHODS: Following informed
      written consent, a prospective observational study of 86 hypertensive patients
      (49 +/- 15 years, 53% male, office SBP 168 +/- 30 mmHg, office DBP 97 +/- 4 mmHg)
      and 20 normotensive controls (48 +/- 13 years, 55% male, office SBP 130 +/- 13
      mmHg, office DBP 80 +/- 11 mmHg) at 1.5-T cardiovascular magnetic resonance was
      conducted. Extracellular volume fraction (ECV) was calculated by T1-mapping. LA
      volume (LAV) was measured with biplane area-length method. LA reservoir, conduit
      and pump function were calculated with the phasic volumetric method. RESULTS:
      Indexed LAV correlated with indexed LV mass (R = 0.376, p < 0.0001) and ECV (R =
      0.359, p = 0.001). However, ECV was the strongest significant predictor of LAE in
      multivariate regression analysis (odds ratio [95th confidence interval] 1.24
      [1.04-1.48], p = 0.017). Indexed myocardial interstitial volume was associated
      with significant reductions in LA reservoir (R = -0.437, p < 0.0001) and conduit
      (R = -0.316, p = 0.003) but not pump (R = -0.167, p = 0.125) function. Multiple
      linear regression, correcting for age, gender, BMI, BP and diabetes, showed an
      independent decrease of 3.5% LA total emptying fraction for each 10 ml/m2
      increase in myocardial interstitial volume (standard beta coefficient -3.54, p =
      0.002). CONCLUSIONS: LV extracellular expansion is associated with LAE and
      impaired LA reservoir and conduit function. Future studies should identify if
      targeting diffuse LV fibrosis is beneficial in reverse remodelling of LA
      structural and functional pathological abnormalities in hypertension. KEY POINTS:
      * Left atrial enlargement (LAE) and impairment are markers of adverse prognosis
      in systemic hypertension but their pathophysiology is poorly understood. * Left
      ventricular extracellular volume fraction was the strongest independent
      multivariate predictor of LAE and was associated with impaired left atrial
      reservoir and conduit function. * LV interstitial expansion may play a central
      role in the pathophysiology of adverse atrioventricular interaction in systemic
      hypertension.

PMID- 30232516
TI  - Predictive value of flexion and extension diffusion tensor imaging in the early
      stage of cervical myelopathy.
AB  - PURPOSE: Diffusion tensor imaging (DTI) in flexion (F) and extension (E) may
      serve as a sensitive diagnostic tool in early symptoms of myelopathy. The aim of
      this study was to compare values of water diffusion parameters on dynamic
      cervical DTI in early stage of myelopathy. METHODS: Study enrolled 10 patients
      with an early stage of cervical myelopathy, in grade I/II of Nurick
      classification. All subjects were scanned with flexion-extension 3T MRI.
      Fractional anisotropy (FA), apparent diffusion coefficient (ADC), RD (radial
      diffusivity), AD (axial diffusivity) and TRACEW (trace diffusion) were measured
      at C2, compression level (CL) and C7. Parameters were compared between 3 levels
      and F and E positions. RESULTS: Flexion DTI revealed significant difference only
      for TRACEW between C2 and C7 (105.8 +/- 18.9 vs. 83.7 +/- 14, respectively; p =
      0.0029). Extension DTI showed differences for ADC between CL and C7 (1378.9 +/-
      381.8 vs. 1227.2 +/- 269.2; p = 0.001), reduced FA from 664.6 +/- 56.3 at C2 down
      to 553.1 +/- 75.5 (p = 0.001) at CL and 584.7 +/- 40.7 at C7 (p = 0.002).
      Differences of RD in E were significant through all levels and reached 612.9 +/-
      105.1, 955.3 +/- 319.4 and 802.1 +/- 194.1 at C2, CL and C7, respectively. TRACEW
      lowered from 92.3 +/- 14.4 at C2 to 66.9 +/- 21.1 at CL (p = 0.0001) and 64.4 +/-
      15.5 at C7 (p = 0.0002). Comparison of DTI between F and E showed differences for
      all parameters except AD. RD was significantly higher in E at CL (p = 0.003) and
      C7 (0.013), but TRACEW increased in F at CL by 27.4% (p = 0.001) and at C7 by
      23.1% (p = 0.013). FA was reduced at CL in E (p = 0.027) and similarly ADC in F
      (p = 0.048). CONCLUSION: Dynamic DTI of the cervical spine is feasible and can
      detect subtle spinal cord damage of functional relevance in cervical myelopathy.
      A marked increase of RD and decrease of FA and TRACEW values in extension were
      found to be indicative for an early structural cord injury in myelopathy.

PMID- 30232517
TI  - Radiomics features to distinguish glioblastoma from primary central nervous
      system lymphoma on multi-parametric MRI.
AB  - PURPOSE: To determine the feasibility of using high dimensional computer
      extracted features, known as radiomics features, in differentiating primary
      central nervous system lymphoma (PCNSL) from glioblastoma on multi-parametric MR
      imaging including diffusion-weighted imaging. METHODS: Retrospective evaluation
      of data was approved by the local ethics committee and informed consent was
      waived. A total of 143 patients (two independent cohorts for discovery [n = 86;
      glioblastoma = 49, PCNSL = 37] and validation [n = 57; glioblastoma = 29, PCNSL =
      28]) with newly diagnosed glioblastoma and PCNSL were subjected to radiomics
      analysis using the multi-parametric MRI (contrast-enhanced T1-weighted imaging,
      T2-weighted imaging, and diffusion-weighted imaging). Radiomics analyses were
      performed for two types of regions of interest (ROI) covering contrast-enhancing
      tumor and whole (enhancing or non-enhancing) tumor plus peritumoral edema. A
      total of 127 radiomics features were calculated. Feature selection was performed
      to identify the most discriminating features for every MR image in the discovery
      cohort. The identified features were used to calculate radiomics scores, which
      were later used in logistic regression to distinguish between PCNSL and
      glioblastoma. The classification model was further tested on the independent
      validation cohort. RESULTS: Fifteen features were selected as significant
      features in the discovery cohort. Using the identified features and calculated
      radiomics scores, the logistic regression-based classifier yielded an area under
      the curve (AUC) of 0.979, sensitivity of 0.938, and specificity of 0.944 in the
      discovery cohort to distinguish between glioblastoma and PCNSL. A similarly high
      rate of performance was observed in the validation cohort (AUC = 0.956).
      CONCLUSIONS: Radiomics features derived from multi-parametric MRI can be used to
      differentiate PCNSL from glioblastoma effectively.

PMID- 30232518
TI  - Conventional, diffusion, and permeability MR findings in ocular
      medulloepithelioma.
AB  - PURPOSE: To describe the neuroradiological features of intraocular
      medulloepithelioma. METHODS: We retrospectively analyzed the clinical,
      histopathological, and MRI data of five children with medulloepithelioma. In
      addition to conventional images, DWI was performed in four patients and mean ADC
      was calculated; this was limited to the technique of this cohort of patients. DCE
      was performed in all patients. This is the first paper that presents diffusion
      and perfusion characteristics of medulloepithelioma. RESULTS: Four tumors were
      malignant teratoid variants, two non-teratoid variants. Tumors were hyperintense
      on T1-weighted images and hypointense on T2-weighted images. Calcifications were
      detectable in two out of five tumors. Cavities were detectable in three out of
      five tumors. All tumors showed some degree of enhancement. The mean ADC of all
      four patients was 1.156 +/- 242.75 * 10-3 mm2/s. Mean ktrans, Ve, Kep, TME, AUC,
      SER, and peak enhancement were 0.082 +/- 0.054, 0.19 +/- 0.076, 0.31 +/- 0.084,
      0.97 +/- 0.0784, 1.22 +/- 0.81, 67.34 +/- 31.7, and 14.84 +/- 7.34 respectively.
      TICs showed a very high ratio of slow increase, > 50% persistence and some degree
      of wash out. Teratoid variants showed higher K-trans, AUC, VE, TME, and
      persistent TIC pattern than non-teratoid ones, while plateau pattern ratio was
      lower. CONCLUSION: Conventional MR findings were similar to previously reported
      cases. Mean ADCs were moderately high. TICs showed slow increase and presence of
      wash out. K-trans, AUC, VE, and TME were higher in teratoid variants.
      Permeability parameters in differential diagnosis with lesions mimicking
      medulloepithelioma need further investigations.

PMID- 30232519
TI  - TIGIT: a novel immunotherapy target moving from bench to bedside.
AB  - Treatment strategies for patients with advanced solid tumors have traditionally
      been based on three different paradigms: surgery, cytotoxics (chemotherapy or
      radiation therapy) and targeted therapies. Immunotherapy has emerged as a novel
      treatment paradigm in our armamentarium. Unfortunately, most patients still do
      not benefit from immunotherapy. These patients often have "cold tumors"
      characterized by a paucity of effector T cells in the tumor microenvironment, low
      mutational load, low neoantigen burden and often an immunosuppressive tumor
      microenvironment. TIGIT is an immunoreceptor inhibitory checkpoint that has been
      implicated in tumor immunosurveillance. Expression of TIGIT has been demonstrated
      in both NK cells and T cells and plays a role in their activation and maturation.
      TIGIT competes with immunoactivator receptor CD226 (DNAM-1) for the same set of
      ligands: CD155 (PVR or poliovirus receptor) and CD112 (Nectin-2 or PVRL2).
      TIGIT's role in tumor immunosurveillance is analogous to the PD-1/PD-L1 axis in
      tumor immunosuppression. Both TIGIT and PD-1 are upregulated in a variety of
      different cancers. Anti-TIGIT antibodies have demonstrated synergy with anti-PD
      1/PD-L1 antibodies in pre-clinical models. Currently, there are multiple first-in
      man phase I trials hoping to exploit this new pathway and improve response rates
      with existing immunotherapies.

PMID- 30232520
TI  - Sustained efficacy of adjuvant immunotherapy with cytokine-induced killer cells
      for hepatocellular carcinoma: an extended 5-year follow-up.
AB  - Our earlier multicenter randomized controlled trial showed that adjuvant
      immunotherapy with cytokine-induced killer (CIK) cells resulted in longer
      recurrence-free survival (RFS) and overall survival (OS) as well in patients who
      received curative treatment for hepatocellular carcinoma (HCC). In the present
      study, we determined if the efficacy of CIK cell therapy continued after end of
      repeated CIK cell injections. We performed a follow-up study of our preceding
      trial. We included 226 patients: 114 patients in the immunotherapy group
      (injection of 6.4 * 109 CIK cells, 16 times during 60 weeks) and 112 patients in
      the control group (no treatment) after potentially curative treatment for HCC. In
      total, 162 patients (89 of the immunotherapy group and 73 of controls) underwent
      an extended follow-up for 60 months after randomization of the last patient. The
      primary endpoint was RFS, and secondary endpoints included OS. During follow-up
      time of median 68.5 months (interquartile range 45.0-82.2 months), the
      immunotherapy group continued to show a significantly lower risk of recurrence or
      death [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.48-0.94; P = 0.009
      by one-sided log-rank test]. At 5 years, RFS rate was 44.8% in the immunotherapy
      group and 33.1% in the control group. The risk of all-cause death was also lower
      in the immunotherapy group compared to the control group (HR 0.33; 95% CI 0.15
      0.76; P = 0.006). In patients who received curative treatment for HCC, the
      significant improvement in RFS and OS as a result of adjuvant CIK cell
      immunotherapy lasted over 5 years without boosting.

PMID- 30232521
TI  - The role of CCR5 in directing the mobilization and biological function of
      CD11b+Gr1+Ly6Clow polymorphonuclear myeloid cells in cancer.
AB  - Bone marrow (BM) cells of the hematopoietic system, also known as BM-derived
      leukocytes (BMD), are mobilized from the BM to the blood and then colonize tumor
      sites. These cells then become key players in either promoting or regulating the
      development and progression of tumors. Among the cells that suppress anti-tumor
      immunity are regulatory T cells (Tregs), tumor-associated macrophages (TAMS) and
      myeloid-derived suppressor cells (MDSC). MDSC comprise CD11b+Gr1+Ly6Clow
      polymorphonuclear myeloid cells (PMN-MDSC), and CD11b+Gr1+Ly6Chigh monocytic
      myeloid cells (Mo-MDSC). Several studies including ours have identified the CCR2
      CCL2 axis as the key driver of the mobilization of monocytic cells from the BM to
      the blood and later their colonization at the tumor site. The current review
      focuses on the mechanisms by which PMN-MDSC are mobilized from the BM to the
      blood and later to the tumor site, and their clinical implications.

PMID- 30232522
TI  - An ESIPT-based fluorescent probe for the determination of hypochlorous acid
      (HClO): mechanism study and its application in cell imaging.
AB  - A highly selective and sensitive probe for the detection of hypochlorous acid
      (HClO) in real samples was designed and synthesized by using the specific
      reaction between HClO and phenyl azo group. Upon reaction with HClO, the
      nonfluorescent probe generated a highly fluorescent 2-(2-hydroxy-4
      chlorophenyl)benzimidazole (HBI-Cl) fluorophore, which underwent the excited
      state intramolecular proton transfer process to give strong fluorescence turn-on.
      The sensing mechanism, conversion of the nonfluorescent azo moiety into the
      fluorescent derivative of HBI upon reaction with HClO, was verified by
      independent synthesis of HBI-Cl (phifl ~ 0.75). The theoretical computing results
      were in agreement with the experimental results that the azo moiety was the
      reactive site to realize fluorescence detection for HClO. Additionally, the probe
      was successfully utilized to determine HClO in tap water, exogenous HClO in HeLa
      cells, and endogenous HClO in MCF-7 cells with a low detection limit and
      cytotoxicity. Graphical abstract ?.

PMID- 30232523
TI  - Evaluation of fatty acid/alcohol-based hydrophobic deep eutectic solvents as
      media for extracting antibiotics from environmental water.
AB  - Fatty acid/alcohol-based hydrophobic deep eutectic solvents (DESs) have been
      considered to be eco-friendly alternatives to replace conventional hydrophobic
      organic solvents (i.e., halogenated solvents). These novel eco-friendly solvents
      are applied in the extraction and determination of two antibiotics (levofloxacin,
      LOF; ciprofloxacin, COF) in environmental water by liquid-liquid microextraction
      (LLME). Two different families of hydrophobic DESs, one based on fatty acids and
      the other on fatty alcohols, were prepared and applied as a microextraction
      solvent. The study results showed that 1-octanol/ tricaprylylmethylammonium
      chloride-based DES (DES-14) had the best extraction efficiency. The vortex
      assisted method exhibited better extraction efficiency than the heating,
      ultrasound, and microwave auxiliary methods in LLME. The main factors affecting
      the vortex-assisted LLME were optimized statistically using the Box-Behnken
      design (BBD) combined with response surface methodology (RSM). The optimal
      conditions for LOF and COF were as follows: 14:174 MUL DES, 5.7 min vortex
      assisted time, and 8.7% NaCl, w/v. Under these conditions, hydrophobic DES-based
      LLME was established for extraction and determination LOF and COF from
      environmental water, and the extraction recoveries of LOF and COF exceeded 94.8%.
      The proposed hydrophobic DES-based LLME method provides high precision, good
      linearity, acceptable limit of detection (LOD) and limit of quantification (LOQ),
      and satisfactory recoveries for the targets. These results support the potential
      of this method as a new type of extraction medium to replace conventional
      hydrophobic organic solvents in various applications.

PMID- 30232525
TI  - Infection safety of dexamethasone in total hip and total knee arthroplasty: a
      study of eighteen thousand, eight hundred and seventy two operations.
AB  - PURPOSE: Dexamethasone has been shown to prevent post-operative nausea and
      vomiting (PONV) and seems to reduce post-operative pain. Both factors, which can
      extend the hospital stay, delay rehabilitation, and impact patient satisfaction.
      Because of the immunosuppressive and glucose-rising effects of dexamethasone,
      there has been concern of its safety in arthroplasty surgery. The purpose of our
      study was to examine infection safety of dexamethasone in arthroplasty surgery
      with enough large study material to reliably detect a possible, even small,
      difference in infection incidence. METHODS: A total of 18,872 consecutive primary
      and revision hip and knee arthroplasties were analyzed with data gathered from
      clinical information databases and a surgical site infection surveillance
      database with prospective data collection. Also, emergency operations due to
      fractures were included except for hip hemiarthroplasties. RESULTS: During the
      follow-up, 189 (1.0%) prosthetic joint infections (PJIs) occurred: 0.8% after
      primary arthroplasty and 1.9% after revision arthroplasty. Dexamethasone was used
      in 2922 (15.5%) operations. The PJI rate in the dexamethasone group was 1.1%
      (31/2922) and in the non-dexamethasone group 1.0% (161/15950), with no
      significant difference in the risk of PJI between the two groups (OR 1.052, 95%
      CI 0.715-1.548, P = 0.773). CONCLUSIONS: In our study material, the use of a
      single 5-10 mg dose of dexamethasone did not increase the incidence of post
      operative PJI. A low dose of dexamethasone may be safely used to prevent PONV and
      as part of multimodal analgesia on patients undergoing arthroplasty operation.

PMID- 30232526
TI  - Dual offset metaphyseal-filling stems in primary total hip arthroplasty in
      dysplastic hips after a minimum follow-up of ten years.
AB  - PURPOSE: The aim of this study was to assess the long-term performance of tapered
      one-third proximally coated stems in dysplastic hips. METHODS: This study
      included 135 dysplasia patients (150 hips) who underwent a total hip arthroplasty
      and had a minimum follow-up of ten years. Single design tapered stems were used
      in all patients. There were 112 women (83%) and 23 men (17%) with a mean age of
      45 years (23 to 72) at the time of surgery. The mean follow-up was 14.7 years (10
      to 16.8). For clinical evaluation, the Harris Hip Score and Merle D'Aubigne scale
      were used pre-operatively and at the final follow-up. Implant survival was
      calculated using Kaplan-Meier survivorship analysis, with failure defined as a
      component revision for any reason. RESULTS: Overall, one stem was revised for a
      deep infection. There were no other femoral stem revisions secondary to
      loosening, wear, periprosthetic fracture, or instability. Radiographic evaluation
      showed excellent stem osteointegration in all cases. Kaplan-Meier survivorship,
      with stem revision for any reason as the end point, was 98% at 14 years (95%
      confidence interval 92.5 to 99.8). CONCLUSION: This study demonstrates that a
      dual offset tapered stem achieved excellent survivorship and stability, as well
      as good clinical outcome scores with minimal thigh pain and stress shielding in
      patients with arthritis and developmental dysplasia of the hip; a dual offset
      tapered stem may be a suitable option for primary total hip arthroplasty in this
      group.

PMID- 30232524
TI  - Portable detection of serum HER-2 in breast cancer by a pressure-based platform.
AB  - A high serum HER-2 extracellular domain (sHER-2 ECD) level has a reverse
      association with tumor behaviors. In this study, a portable platform for the
      disease biomarker sHER-2 ECD detection has been established using a pressure
      based bioassay. The pressure bioassay consists of a monoclonal antibody
      immobilized on an eight-well strip, the analyte HER-2, and another monoclonal
      antibody labeled with the Pt nanoparticles (PtNPs), which have the catalytic
      ability to decompose H2O2 into H2O and O2(g). The increased pressure due to O2(g)
      generation is measured by a hand-held pressure meter. A total of 34 serum samples
      were collected to validate the performance of the pressure bioassay. The results
      showed that the pressure bioassay platform of HER-2 had a dynamic range from 2 to
      50 ng/mL with a limit of detection (LOD) of 2 ng/mL, which was consistent with
      the ELISA result. In the real serum samples, there was a significant correlation
      between sHER-2 ECD level and several clinicopathological parameters, especially
      tissue HER-2 status. Furthermore, the sHER-2 ECD level was found to decrease
      after targeted therapy in a patient with tHER-2 positive. Overall, this bioassay
      can facilitate breast cancer diagnosis and prognosis in clinical scenarios and
      resource-limited areas.

PMID- 30232527
TI  - Improved patient blood management and cost saving in hip replacement surgery
      through the implementation of pre-operative Sucrosomial(r) iron supplementation:
      a quality improvement assessment study.
AB  - PURPOSE: To compare post-operative recovery of prosthetic hip surgery patients
      with or without the implementation of iron supplementation with a new highly
      absorbable oral iron formulation. METHODS: Observational retrospective quality
      improvement assessment conducted on patients who had undergone elective
      prosthetic hip surgery (first implant) with ferritin < 100 mcg/dl and Hb values
      between 13 and 14 g/dl for men and 12 g/dl and 13.5 g/dl for women, or having
      ferritin levels > 100 mcg/dl but C-reactive protein (CRP) > 3 mg/l and
      transferrin saturation (TSAT) < 20%, which together are suggestive of functional
      iron deficiency. The analysis compared a group of non-anaemic patients having
      ferritin levels > 100 mcg/l to two groups of patients with iron deficiency, of
      which only one received iron supplementation. Measurements included haemoglobin
      levels, length of hospital stay, and number of transfused patients/blood units.
      RESULTS: Patients with iron deficiency supplemented with Sideral(r) Forte
      compared to non-supplemented patients showed a smaller decline in post-operative
      Hb (9.7 +/- 1.24 g/dl vs 8.4 +/- 0.6 g/dl), required shorter hospital stay (4 vs
      6.5 days) and less blood transfusions (0 in the iron-supplemented group vs 7
      units in the non-iron-supplemented group), yielding an overall savings of 1763.25
      ?/patient. CONCLUSIONS: Pre-operative sucrosomial iron supplementation at least 4
      weeks prior to elective surgery in non-anaemic patients limits the drop in post
      operative Hb levels, determining higher post-operative haemoglobin, quicker post
      surgical recovery, shorter hospitalisation, and decreased surgery-related costs.

PMID- 30232529
TI  - Effects of repeated treatment with methcathinone, mephedrone, and fenfluramine on
      intracranial self-stimulation in rats.
AB  - RATIONALE: Synthetic cathinones constitute a class of abused drugs that can act
      at dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT,
      respectively). Intracranial self-stimulation (ICSS) is a preclinical procedure
      that can be used to evaluate abuse potential of drugs, and prior studies have
      indicated that abuse-related ICSS effects of monoamine-transporter substrates,
      including some synthetic cathinones, are positively correlated with drug
      selectivity for DAT vs. SERT. Abuse potential of drugs can also be influenced by
      regimens of repeated drug exposure, but the role of repeated exposure on abuse
      related ICSS effects of synthetic cathinones has not been examined. OBJECTIVES:
      This study used ICSS to evaluate effects of repeated treatment with the DAT>SERT
      substrate methcathinone, the DAT<SERT substrate fenfluramine, and the DAT~SERT
      substrate mephedrone. METHODS: Male Sprague-Dawley rats were trained in a
      frequency-rate ICSS procedure, and different groups were used to evaluate effects
      of methcathinone, mephedrone, and fenfluramine before, during, and after regimens
      of repeated treatment with the designated drug. RESULTS: Before repeated
      treatment, methcathinone produced dose-dependent and abuse-related ICSS
      facilitation, fenfluramine produced dose-dependent ICSS depression, and
      mephedrone produced mixed effects that included both facilitation and depression.
      Chronic treatment produced no change in effects of methcathinone, but complete
      tolerance to effects of fenfluramine. For mephedrone, chronic treatment produced
      partial tolerance to ICSS depression and enhanced expression of ICSS
      facilitation. CONCLUSIONS: Repeated exposure to mixed-action DAT~SERT substrates
      such as mephedrone can result in increased abuse potential due to sustained
      expression of DAT-mediated abuse-related effects and tolerance to SERT-mediated
      abuse-limiting effects.

PMID- 30232528
TI  - Effect of gamma-hydroxybutyrate (GHB) on driving as measured by a driving
      simulator.
AB  - RATIONALE: Gamma-hydroxybutyrate acid (GHB), a GABAB receptor agonist approved
      for treatment of narcolepsy, impairs driving ability, but little is known about
      doses and plasma concentrations associated with impairment and time course of
      recovery. OBJECTIVE: To assess effects of oral GHB (Xyrem(r)) upon driving as
      measured by a driving simulator, and to determine plasma concentrations
      associated with impairment and the time course of recovery. METHODS: Randomized,
      double-blind, two-arm crossover study, during which 16 participants received GHB
      50 mg/kg orally or placebo. GHB blood samples were collected prior to and at 1,
      3, and 6 h post dosing. Driving simulator sessions occurred immediately after
      blood sampling. RESULTS: Plasma GHB was not detectable at baseline or 6 h post
      dosing. Median GHB concentrations at 1 and 3 h were 83.1 mg/L (range 54-110) and
      24.4 mg/L (range 7.2-49.7), respectively. Compared to placebo, at 1 h post GHB
      dosing, significant differences were seen for the life-threatening outcome
      collisions (p < 0.001) and off-road accidents (p = 0.018). Although driving was
      not faster, there was significantly more weaving and erratic driving with GHB as
      measured by speed deviation (p = 0.002) and lane position deviation (p = 0.004).
      No significant impairment regarding driving outcomes was found in the GHB group
      at 3 and 6 h post dose. CONCLUSION: GHB in doses used to treat narcolepsy
      resulted in severe driving impairment at 1 h post dosing. After 3 to 6 h, there
      was full recovery indicating that safe driving is expected the next morning after
      bedtime therapeutic GHB use in the absence of other substances.

PMID- 30232531
TI  - Global Monitoring of Persistent Organic Pollutants (POPs) Using Seabird Preen
      Gland Oil.
AB  - Situated at high positions on marine food webs, seabirds accumulate high
      concentrations of persistent organic pollutants (POPs), such as polychlorinated
      biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), and
      hexachlorocyclohexanes (HCHs). Our previous studies proposed the usefulness of
      seabirds preen gland oil as a nondestructive biomonitoring tool. The present
      study applied this approach to 154 adult birds of 24 species collected from 11
      locations during 2005-2016 to demonstrate the utility of preen gland oil as a
      tool for global monitoring POPs, i.e., PCBs, DDTs, and HCHs. Concentrations of
      the POPs were higher in the Northern Hemisphere than in the Southern Hemisphere.
      In particular, ?20PCBs and?DDTs were highly concentrated in European shags
      (Phalacrocorax aristotelis) and Japanese cormorants (Phalacrocorax capillatus),
      explainable by a diet of benthic fishes. Higher concentrations of gamma-HCH were
      detected in species from the polar regions, possibly reflecting the recent
      exposure and global distillation of ?HCHs. We examined the relationship between
      age and POP concentrations in preen gland oil from 20 male European shags, aged 3
      16 years old. Concentrations and compositions of POPs were not related to age. We
      also examined sex differences in the POP concentrations from 24 streaked
      shearwaters (Calonectris leucomelas) and did not detect a sex bias. These results
      underline the importance of the geographic concentration patterns and the dietary
      behavior as determinants species-specific POPs concentrations in preen gland oil.

PMID- 30232532
TI  - Detection of pediatric musculoskeletal pathology using the fluid-sensitive
      sequence.
AB  - BACKGROUND: Musculoskeletal complaints are common among children, and magnetic
      resonance (MR) is increasingly used to supplement the clinical assessment. The
      validation of a short triage protocol could reduce the number of unnecessary
      contrast-enhanced MR studies that sometimes also require the need for sedation.
      OBJECTIVE: To compare the diagnostic accuracy between fluid-sensitive sequence
      and contrast-enhanced MR study in the detection of musculoskeletal pathology in
      the pelvis and the appendicular skeleton in children older than 2 years.
      MATERIALS AND METHODS: We performed a retrospective review between Feb. 1, 2016,
      and Oct. 31, 2016, and identified 99 studies from 96 patients (48 boys and 48
      girls; mean age +/- standard deviation, 11.1+/-4.6 years) without syndromic
      deformity, recent trauma, a history of infectious or inflammatory arthropathy,
      prior instrumentation or incomplete records. Two radiologists reviewed each study
      twice, at least 1 month apart, first using only the fluid-sensitive sequences
      (triage study) and later using the contrast-enhanced study. Readers rated the
      presence or absence of pathology independently and generated final impressions in
      consensus. We used Cohen's kappa (kappa) and percentage agreement to compare
      agreement between readers and between studies, respectively. RESULTS: Inter
      reader agreement was overall higher for the contrast-enhanced studies (kappa
      range = 0.91-1) than for the triage studies (kappa range = 0.49-1). Percentage
      agreement between studies was high for the detection of pathology (97-100%) and
      for the impressions (93%). Clinical diagnoses were stress reaction or overuse in
      31%, infection in 21%, space-occupying process in 17%, normal in 15%,
      inflammatory in 14%, and both inflammatory and overuse in 1%. The full study
      increased diagnostic confidence in five studies and accuracy in two but did not
      alter management. CONCLUSION: The fluid-sensitive sequence had a near-perfect
      percentage of agreement with the contrast-enhanced study in the detection of
      musculoskeletal pathology and could possibly be used to screen children who need
      a contrast-enhanced MR study.

PMID- 30232530
TI  - Benzodiazepines and risk of pneumonia in schizophrenia: a nationwide case-control
      study.
AB  - OBJECTIVES: To investigate the relationship between benzodiazepine and risk of
      developing pneumonia in patients with schizophrenia, whose benzodiazepine dosage
      and usage frequency was higher than that of the general population. METHODS: We
      conducted a nested case-control study to assess the association between
      benzodiazepine use and pneumonia among patients with schizophrenia. By using the
      Taiwan National Health Insurance Research Database, we identified a schizophrenia
      cohort comprising 34,929 patients during 2000-2010. Within the schizophrenia
      cohort, 2501 cases of pneumonia and 9961 matched control patients (1:4 ratio)
      were identified. Benzodiazepine exposure was categorized by drug, treatment
      duration, and daily dose. Conditional logistic regression models were used to
      examine the association between benzodiazepine exposure and the risk of
      pneumonia. RESULTS: The current use (within 30 days) of midazolam led to the
      highest pneumonia risk (adjusted risk ratio = 6.56, P < 0.001), followed by
      diazepam (3.43, P < 0.001), lorazepam (2.16, P < 0.001), and triazolam (1.80, P =
      0.019). Furthermore, nearly all the benzodiazepines under current use had a dose
      dependent effect on pneumonia risk. The risk of pneumonia was correlated with the
      affinities of gamma-aminobutyric acid A alpha1, alpha2, and alpha3 receptors.
      CONCLUSIONS: Benzodiazepines had a dose-dependent relationship with pneumonia in
      patients with schizophrenia. The differences in risk and mechanism of action of
      the individual drugs require further investigation. Clinicians should be aware of
      the early signs of pneumonia in patients with schizophrenia receiving
      benzodiazepines.

PMID- 30232533
TI  - Pediatric ileocolic intussusception: new observations and unexpected
      implications.
AB  - BACKGROUND: Ileocolic intussusception occurs when the terminal ileum "telescopes"
      into the colon. We observed that ileocolic intussusception lengths are similar
      regardless of location in the colon. OBJECTIVE: To examine the uniformity of
      ileocolic intussusception length and its relationship to colon location, symptom
      duration and reducibility. MATERIALS AND METHODS: We retrospectively reviewed
      ultrasound-diagnosed pediatric ileocolic intussusceptions initially treated with
      pneumatic reduction at the Mayo Clinic or Texas Children's Hospital. We recorded
      demographic, imaging and surgical findings including age, gender, symptom
      duration, location of the ileocolic intussusception, reducibility with air enema
      and, if fluoroscopically irreducible, surgical findings. RESULTS: We identified
      119 ileocolic intussusceptions (64% boys), with 81% in the right colon. There was
      no significant relationship between ileocolic intussusception length and colon
      location (P=0.15), nor ileocolic intussusception length and symptom duration
      (P=0.36). Ileocolic intussusceptions were more distal with increasing symptom
      duration (P=0.016). Successful reductions were unrelated to symptom duration
      (P=0.84) but were more likely with proximal versus distal locations (P=0.02).
      CONCLUSION: Ileocolic intussusception lengths are relatively uniform regardless
      of location along the course of the colon where they present. Our findings
      suggest that most of the apparent distal propagation of ileocolic
      intussusceptions is not caused by increasing telescoping of small bowel across
      the ileocecal valve but rather by foreshortening of the right colon. This implies
      poor cecal fixation and confirms fluoroscopic and surgical observations of cecal
      displacement from the right lower quadrant with ileocolic intussusceptions. The
      movement of the leading edge of the ileocolic intussusception during reduction is
      first due to "relocating" the cecum into the right lower quadrant after which the
      reduction of small bowel back across the ileocecal valve then occurs.

PMID- 30232534
TI  - Genome mining of Streptomyces xinghaiensis NRRL B-24674T for the discovery of the
      gene cluster involved in anticomplement activities and detection of novel
      xiamycin analogs.
AB  - Marine actinobacterium Streptomyces xinghaiensis NRRL B-24674T has been
      characterized as a novel species, but thus far, its biosynthetic potential
      remains unexplored. In this study, the high-quality genome sequence of S.
      xinghaiensis NRRL B-24674T was obtained, and the production of anticomplement
      agents, xiamycin analogs, and siderophores was investigated by genome mining.
      Anticomplement compounds are valuable for combating numerous diseases caused by
      the abnormal activation of the human complement system. The biosynthetic gene
      cluster (BGC) nrps1 resembles that of complestatins, which are potent microbial
      derived anticomplement agents. The identification of the nrps1 BGC revealed a
      core peptide that differed from that in complestatin; thus, we studied the
      anticomplement activity of this strain. The culture broth of S. xinghaiensis NRRL
      B-24674T displayed good anticomplement activity. Subsequently, the disruption of
      the genes in the nrps1 BGC resulted in the loss of anticomplement activity,
      confirming the involvement of this BGC in the biosynthesis of anticomplement
      agents. In addition, the mining of the BGC tep5, which resembles that of the
      antiviral pentacyclic indolosesquiterpene xiamycin, resulted in the discovery of
      nine xiamycin analogs, including three novel compounds. In addition to the BGCs
      responsible for desferrioxamine B, neomycin, ectoine, and carotenoid, 18 BGCs
      present in the genome are predicted to be novel. The results of this study unveil
      the potential of S. xinghaiensis as a producer of novel anticomplement agents and
      provide a basis for further exploration of the biosynthetic potential of S.
      xinghaiensis NRRL B-24674T for the discovery of novel bioactive compounds by
      genome mining.

PMID- 30232535
TI  - Classification of fungal glucuronoyl esterases (FGEs) and characterization of two
      new FGEs from Ceriporiopsis subvermispora and Pleurotus eryngii.
AB  - Fungal glucuronoyl esterases (FGEs) catalyze cleavage of the ester bond
      connecting a lignin alcohol to the xylan-bound 4-O-methyl-D-glucuronic acid of
      glucuronoxylans. Thus, FGEs are capable of degrading lignin-carbohydrate
      complexes and have potential for biotechnological applications toward woody
      biomass utilization. Therefore, identification and characterization of new FGEs
      are of critical importance. Firstly, in this study, we built a phylogenetic tree
      from almost 400 putative FGEs obtained on BLAST analysis and defined six main
      clades. In the phylogenetic tree, all the putative FGEs of ascomycetes cluster in
      clades I to IV, and most of the putative FGEs of basidiomycetes (B-FGEs) cluster
      in clades V to VI. Interestingly, several B-FGEs were found to cluster in clade
      II; most FGEs of clade II were found to have higher theoretical isoelectric
      points than those in the other five clades. To gain an insight into the putative
      FGEs in the clades that have not been characterized yet, we chose the FGEs of
      Ceriporiopsis subvermispora (CsGE) and Pleurotus eryngii (PeGE), which belong to
      clades V and II, respectively. The catalytic domains of both CsGE and PeGE were
      successfully expressed using Pichia pastoris, and then purified. Benzyl
      glucuronic acid was used as a substrate to confirm the activities of the CsGE and
      PeGE, and the hydrolyzed product, glucuronic acid, was quantified
      spectrophotometrically. Both CsGE and PeGE clearly exhibited the esterase
      activity. Additionally, we demonstrated that PeGE exhibits high tolerance toward
      several denaturing agents, which may make it a potentially more applicable
      enzyme.

PMID- 30232536
TI  - Lactic acid fermentation is the main aerobic metabolic pathway in Enterococcus
      faecalis metabolizing a high concentration of glycerol.
AB  - Bacterial lactate production by fermentative lactate dehydrogenase is generally
      activated under anaerobic conditions. However, when the Enterococcus faecalis
      strain W11 was cultured with a high concentration of glycerol (1.0 M), but not
      with glucose, up to 0.95 M L-lactate was produced from 1.0 M glycerol via the
      fermentative L-lactate dehydrogenase (LdhL1) reaction despite the abundant supply
      of oxygen. To understand the underlying mechanism, transcription, metabolic
      products, and intracellular NADH/total NAD (tNAD) ratio of W11 were analyzed. The
      ldhL1 transcription was constitutive and not markedly affected by dissolved
      oxygen level or NADH/tNAD ratio. Conversely, gene transcription and enzyme
      activities related to other pyruvate metabolic pathways, namely the acetoin,
      acetate, and ethanol production pathways, in W11 utilizing 1.0 M glycerol tended
      to be downregulated or inactivated by a high NADH/tNAD ratio or supply of oxygen.
      These findings indicated that the amount and yield of L-lactate depended on the
      activity levels of other metabolic pathways and that lactic acid fermentation was
      the main aerobic metabolic pathway in W11 utilizing glycerol at a high
      concentration. This phenomenon enabled W11 to produce up to 1.50 M and 1.15 M L
      lactate from glycerol and crude glycerol with a high yield, respectively, and
      these production amounts were higher than those in previous studies.

PMID- 30232537
TI  - Impact of prescription drugs on second fragility fractures among US Medicare
      patients.
AB  - : Drugs that increase the risk of fracture are commonly prescribed to survivors
      of a fragility fracture. This study shows that starting new high-risk medications
      after fracture increases the risk of a second, potentially preventable fracture.
      For most drug classes, however, it is safe to continue medications taken before
      the fracture. INTRODUCTION: Most patients who survive a fragility fracture are
      subsequently exposed to prescription drugs that have been linked to increased
      fracture risk. This study was designed to quantify the extent to which current
      prescribing practices result in potentially preventable second fractures.
      METHODS: We analyzed a cohort of 138,526 Medicare beneficiaries who returned to
      the community after a fragility fracture. Post-fracture drug use was defined
      using retail pharmacy fills. The risk of second fracture associated with
      individual drug classes was analyzed using Cox proportional hazard models. Data
      were further analyzed to determine whether there is a difference in risk between
      continuing previous therapy and initiating new therapy after fracture. RESULTS:
      Many drug classes previously identified as increasing fracture risk were not
      associated with increased fracture risk in this cohort. Discontinuing therapy at
      the time of fracture was only beneficial for patients taking selective serotonin
      reuptake inhibitors; however, initiating therapy in previous non-users increased
      second fracture risk for five classes of drugs (selective serotonin reuptake
      inhibitors, tricyclic antidepressants, antipsychotics, proton pump inhibitors,
      and non-benzodiazepine hypnotics). CONCLUSION: Discontinuing high-risk drugs
      after fracture was not generally protective against subsequent fractures.
      Preventing the addition of new medications may result in greater improvements in
      post-fracture care.

PMID- 30232538
TI  - Adherence to osteoporosis therapy after an upper extremity fracture: a pre
      specified substudy of the C-STOP randomized controlled trial.
AB  - : Despite their proven efficacy for secondary fracture prevention, long-term
      adherence with oral bisphosphonates is poor. INTRODUCTION: To compare the
      effectiveness of two interventions on long-term oral bisphosphonate adherence
      after an upper extremity fragility fracture. METHODS: Community-dwelling
      participants 50 years or older with upper extremity fragility fractures not
      previously treated with bisphosphonates were randomized to either a multi-faceted
      patient and physician educational intervention (the active control arm) vs. a
      nurse-led case manager (the study arm). Primary outcome was adherence (taking >
      80% of prescribed doses) with prescribed oral bisphosphonates at 12 months
      postfracture between groups; secondary outcomes included rates of primary non
      adherence and 24-month adherence. We also compared quality of life between
      adherent and non-adherent patients. RESULTS: By 12 months, adherence with the
      initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48
      (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case
      manager arm. By 24 months, adherence rates were 67% (32/48) in the educational
      intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary
      non-adherence was 6% (11 patients) in the educational intervention group and 12%
      (21 patients) in the case managed group (p = 0.07). Prior family history of
      osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current
      medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence
      while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income <
      $30,000 per annum) was associated with poorer rates of adherence. There were no
      differences in health-related quality of life scores at baseline or during follow
      up between patients who were adherent and those who were not. CONCLUSION: While
      both interventions achieved higher oral bisphosphonate adherence compared to
      previously reported adherence rates in the general population, primary non
      adherence and long-term adherence to bisphosphonates were similar in both arms.
      Adherence was influenced by family history of osteoporosis, satisfaction with
      current medical care, and income. TRIAL REGISTRATION: ClinicalTrials.gov :
      NCT01401556.

PMID- 30232539
TI  - 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a
      pilot study.
AB  - BACKGROUND: A remarkable therapeutic efficacy has been demonstrated with 225Ac
      prostate-specific membrane antigen (PSMA)-617 in heavily pre-treated metastatic
      castration-resistant prostate cancer (mCRPC) patients. We report our experience
      with 225Ac-PSMA-617 therapy in chemotherapy-naive patients with advanced
      metastatic prostate carcinoma. METHODS: Seventeen patients with advanced prostate
      cancer were selected for treatment with 225Ac-PSMA-617 in 2-month intervals, with
      initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases
      of good response. In one patient, activity was escalated to 13 MBq in the third
      cycle. Fourteen patients had three treatment cycles administered, while in three
      patients treatment was discontinued after two cycles due to good response. Six
      out of 17 patients received additional treatments after the third cycle. Prostate
      specific antigen (PSA) was measured every 4 weeks for PSA response assessment.
      68Ga-PSMA-PET/CT was used for functional response assessment before each
      subsequent treatment cycle. Serial full blood count, renal function test, and
      liver function were obtained to determine treatment-related side effects.
      RESULTS: Good antitumor activity assessed by serum PSA level and 68Ga-PSMA-PET/CT
      was seen in 16/17 patients. In 14/17 patients, PSA decline >=90% was seen after
      treatment, including seven patients with undetectable serum PSA following two
      (2/7) or three cycles (5/7) cycles of 225Ac-PSMA-617. Fifteen of 17 patients had
      a > 50% decline in lesions avidity for tracer on 68Ga-PSMA-PET/CT including 11
      patients with complete resolution (PET-negative and either stable sclerosis on CT
      for bone or resolution of lymph node metastases) of all metastatic lesions. Grade
      1/2 xerostomia was seen in all patients, and none was severe enough to lead to
      discontinuation of treatment. One patient had with extensive bone marrow
      metastases and a background anemia developed a grade 3 anemia while another
      patient with solitary kidney and pre-treatment grade 3 renal failure developed
      grade 4 renal toxicity following treatment. The group presented with significant
      palliation of bone pain and reduced toxicity to salivary glands due to de
      escalation. CONCLUSIONS: 225Ac-PSMA-617 RLT of chemotherapy-naive patients with
      advanced metastatic prostate carcinoma led to a >= 90% decline in serum PSA in
      82% of patients including 41% of patients with undetectable serum PSA who
      remained in remission 12 months after therapy. The remarkable therapeutic
      efficacy reported in this study could be achieved with reduced toxicity to
      salivary glands due to de-escalation of administered activities in subsequent
      treatment cycles. This necessitates further exploration for informing clinical
      practice and clinical trial design.

PMID- 30232540
TI  - The influence of PSA flare in mCRPC patients treated with alpha-emitting
      radiopharmaceuticals.

PMID- 30232541
TI  - Changing trends in the use of cartilage restoration techniques for the
      patellofemoral joint: a systematic review.
AB  - PURPOSE: The patellofemoral (PF) joint contains the thickest articular cartilage
      in the human body. Chondral lesions to this area are often misdiagnosed and can
      predispose to secondary osteoarthritis if left untreated. Treatment options range
      from arthroscopic debridement to cartilage restoration techniques such as
      microfracture (MFx), autologous chondrocyte implantation (ACI), and osteochondral
      autograft transplantation. The purpose of this study was to systematically assess
      the trends in surgical techniques, outcomes, and complications of cartilage
      restoration of the PF joint. METHODS: This review has been conducted according to
      the guidelines of Preferred Reporting Items for Systematic Reviews and Meta
      analyses (PRISMA). The electronic databases PubMed, MEDLINE, and EMBASE were
      searched from January 1, 2007 to April 30, 2018. The Methodological Index for Non
      randomized Studies (MINORS) was used to assess study quality. A two-proportion z
      test was used to determine whether the differences between the proportions of
      cartilage restoration techniques used from 2007 to 2012 and 2013-2018 were
      statistically significant. RESULTS: Overall, 28 studies were identified,
      including 708 patients (824 knees) with a mean age of 39.5 +/- 10.5 years and a
      mean follow-up of 39.1 +/- 16.0 months. Majority of patients were treated with
      ACI (45.5%) and MFx (29.6%). A significant increase in the use of the third
      generation ACI occurred with a simultaneous decreased usage of the conventional
      MFx over the last 5 years (p < 0.001). All techniques had significant (p < 0.05)
      improvements in clinical outcomes. The overall complication rate was 9.2%, of
      which graft hypertrophy (2.7%) was the most prevalent. CONCLUSIONS: ACI was the
      most common restoration technique. The use of third generation ACI has increased
      with a concurrent decline in the use of conventional MFx over the latter half of
      the past decade (p < 0.001). Overall, the various cartilage restoration
      techniques reported improvements in patient reported outcomes with low
      complication rates. Definitive conclusions on the optimal treatment remain
      elusive due to a lack of high-quality comparative studies. LEVEL OF EVIDENCE:
      Level IV, Systematic Review of Level-II-IV studies.

PMID- 30232542
TI  - Correction to: Factors associated with poorer outcomes in the surgical treatment
      of multiligament knee injuries.
AB  - The author would like to correct the following errors in the publication of the
      original article.

PMID- 30232545
TI  - Care for children with dental neglect: identification of problems and approaches
      to solving them.
AB  - Dental neglect may have serious consequences for children's health. Moreover, it
      may indicate general negligence and it can be associated with child abuse.
      Therefore, a highly professional case management is of utmost importance, but
      also poses a great challenge for dentists. In order to develop effective
      strategies for an optimization of dental care in cases of dental neglect, a
      better understanding of the situation, and in particular an investigation into
      the unsolved questions of dentists in these cases, is needed. A prospective
      clinical examination with ten dentists was carried out to identify their
      challenges in the treatment of and the care for children facing suspicion of
      dental neglect. The practice of dental care in the cases of 102 children with
      suspicion of dental neglect (ages 3-14 years) was analyzed by collecting
      quantitative data (questionnaires) as well as qualitative data (focus group
      interviews). Severe and complex challenges in the handling of dental neglect in
      dental practice were identified. The study revealed that steps towards an
      optimization of the care for children with suspicion on dental neglect, which is
      much more than the treatment of caries, are needed. As such steps, we propose (1)
      the drafting of precise guidelines, (2) the education and training of dental
      students and dentists in general, (3) mandatory periodical dental health
      screenings, (4) the establishment of an interdisciplinary cooperation within the
      public health system, (5) the education of families, and (6) an adequate
      financial compensation for a professional and optimized case management. The
      establishment of efficient strategies of prevention and treatment of dental
      neglect and associated risks for the health of affected children will only be
      achieved with intense public and governmental support.

PMID- 30232543
TI  - Ameliorating the adverse cardiorespiratory effects of chemical immobilization by
      inducing general anaesthesia in sheep and goats: implications for physiological
      studies of large wild mammals.
AB  - Chemical immobilization is necessary for the physiological study of large wild
      animals. However, the immobilizing drugs can adversely affect the cardiovascular
      and respiratory systems, yielding data that do not accurately represent the
      normal, resting state. We hypothesize that these adverse effects can be
      ameliorated by reversing the immobilizing agent while holding the animal under
      general anaesthesia. We used habituated sheep Ovis aries (N = 5, 46.9 +/- 5.3 kg
      body mass, mean +/- SEM) and goats Capra hircus (N = 4, 27.7 +/- 2.8 kg) as
      ungulate models for large wild animals, and measured their cardiorespiratory
      function under three conditions: (1) mild sedation (midazolam), as a proxy for
      the normal resting state, (2) immobilization (etorphine and azaperone), and (3)
      general anaesthesia (propofol) followed by etorphine antagonism (naltrexone).
      Cardiac output for both sheep and goats remained unchanged across the three
      conditions (overall means of 6.2 +/- 0.9 and 3.3 +/- 0.3 L min-1, respectively).
      For both sheep and goats, systemic and pulmonary mean arterial pressures were
      significantly altered from initial midazolam levels when administered etorphine +
      azaperone, but those arterial pressures were restored upon transition to propofol
      anaesthesia and antagonism of the etorphine. Under etorphine + azaperone, minute
      ventilation decreased in the sheep, though this decrease was corrected under
      propofol, while the minute ventilation in the goats remained unchanged
      throughout. Under etorphine + azaperone, both sheep and goats displayed arterial
      blood hypoxia and hypercapnia (relative to midazolam levels), which failed to
      completely recover under propofol, indicating that more time might be needed for
      the blood gases to be adequately restored. Nonetheless, many of the confounding
      cardiorespiratory effects of etorphine were ameliorated when it was antagonized
      with naltrexone while the animal was held under propofol, indicating that this
      procedure can largely restore the cardiovascular and respiratory systems closer
      to a normal, resting state.

PMID- 30232546
TI  - Exploring the temporal boundary conditions of the articulatory in-out preference
      effect.
AB  - Earlier research has documented a preference for words with consonantal
      articulation patterns that move from the front to the back of the mouth (e.g.,
      MENIKA) over words with reversely wandering consonantal articulation spots (e.g.,
      KENIMA). The present experiments explored the temporal dynamics of the reading
      process in this in-out preference effect. In three experiments (total N = 344),
      we gradually reduced the presentation durations of inward and outward wandering
      words from 1000 ms down to 25 ms to approximate the minimum length of visual
      stimulus presentation required to trigger the effect. The in-out effect was
      reliably observed for exposure timings down to 50 ms, but vanished for 25 ms
      timings, which is line with previous evidence on phonological encoding. Thus,
      impressively, 50 ms of word presentation is sufficient to evoke the in-out
      effect. These findings suggest phonological activation to be a prerequisite and
      thus a driving mechanism of the in-out effect.

PMID- 30232544
TI  - Is the third molar maturity index (I3M) useful for a genetic isolate population?
      Study of a Sardinian sample of children and young adults.
AB  - This work aims to assess the validity of the cut-off value (0.08) of the third
      molar maturity index (I3M) for discriminating minors from adults in Sardinian
      population. A sample of 336 digital panoramic radiographs of healthy Sardinian
      children and young minors (165 females and 171 males), aged between 15 and 23
      years (mean age, 19.35 years in females and 18.80 years in males), was
      retrospectively evaluated. The left lower third molars were analysed by applying
      a specific cut-off value of 0.08 determined by Cameriere et al. in 2008. The
      reliability and reproducibility of the test was also studied: the intra-class
      correlation coefficients (ICC) were 0.91 (95% CI, 0.89-0.93) and 0.88 (95% CI,
      0.86-0.90), for the intra- and inter-observer reliability, respectively. The I3M
      gradually decreased as the real age gradually increased in both sexes. According
      to the pooled results of the diagnostic test, the accuracy (ACC) was 0.86 (95%
      CI, 0.82-0.89); the proportion of correctly classified subjects (Se =
      sensitivity) was 0.82 (95% CI: 0.76-0.86); and specificity (Sp = specificity) was
      0.95 (95% CI, 0.89-0.97). The positive predictive values (PPV) and the negative
      predictive values (NPVs) were 0.97 (95% CI, 0.94-0.99) and 0.70 (95% CI, 0.62
      0.77). The LR+ and the LR- were 17.12 (95% CI, 7.27 to 40.36) and 0.19 (95% CI,
      0.14 to 0.25). In spite of this, significant differences in the early
      mineralisation of the third molar were found between sexes as well as in the
      results of the diagnostic test, showing a better sensitivity in males than in
      females. The results showed that, although the third molar teeth are highly
      variable in development, and with differences between females and males as
      compare to other teeth, the I3M is a reliable method to distinguish between
      minors and adults even in such a genetic isolate population.

PMID- 30232547
TI  - Auditory-vocal coupling in the naked mole-rat, a mammal with poor auditory
      thresholds.
AB  - Naked mole-rats are extremely social and extremely vocal rodents, displaying a
      wide range of functionally distinct call types and vocalizing almost
      continuously. Their vocalizations are low frequency, and a behavioral audiogram
      has shown that naked mole-rats, like other subterranean mammals, hear only low
      frequencies. Hence, the frequency range of their hearing and vocalizations
      appears to be well matched. However, even at low frequencies, naked mole-rats
      show very poor auditory thresholds, suggesting vocal communication may be
      effective only over short distances. However, in a tunnel environment where low
      frequency sounds propagate well and background noise is low, it may be that
      vocalizations travel considerable distances at suprathreshold intensities. Here,
      we confirmed hearing sensitivity using the auditory brainstem response; we
      characterized signature and alarm calls in intensity and frequency domains and we
      measured the effects of propagation through tubes with the diameter of naked mole
      rat tunnels. Signature calls-used for intimate communication-could travel 3-8 m
      at suprathreshold intensities, and alarm calls (lower frequency and higher
      intensity), could travel up to 15 m. Despite this species' poor hearing
      sensitivity, the naked mole-rat displays a functional, coupled auditory-vocal
      communication system-a hallmark principle of acoustic communication systems
      across taxa.

PMID- 30232549
TI  - Eating and Drinking Ability Classification System.

PMID- 30232548
TI  - CoQ10-related sustained remission of proteinuria in a child with COQ6
      glomerulopathy-a case report.
AB  - BACKGROUND: Treatment of steroid resistant nephrotic syndrome is still a
      challenge for physicians. There are a growing number of studies exploring genetic
      background of steroid-resistant glomerulopathies. CASE DIAGNOSIS/TREATMENT: We
      present the case of a 4-year-old girl with steroid-resistant glomerulopathy due
      to a COQ6 defect with no additional systemic symptoms. The disease did not
      respond for second-line therapy with calcineurin inhibitor, but it remitted
      completely after oral treatment with 30 mg/kg/d of coenzyme Q10 (CoQ10). The
      patient was identified to be a compound heterozygote for two pathogenic variants
      in COQ6 gene: a known missense substitution c.1078C > T (p.R360W) and a novel
      frameshift c.804delC mutation. After 12 months of CoQ10 therapy, the child
      remains in full remission, her physical development accelerated, frequent
      respiratory airways diseases subsided. CONCLUSIONS: Genetic assessment of
      children with steroid-resistant nephrotic proteinuria enables therapy
      optimization. Proteinuria caused by a COQ6 gene defect can be successfully
      treated with CoQ10.

PMID- 30232550
TI  - Correlates of Early Pharyngeal High-Resolution Manometry Adoption in Expert
      Speech-Language Pathologists.
AB  - Pharyngeal high-resolution manometry (HRM) is at a point of entry into speech
      language pathologist (SLP) clinical practice. However, the demographic
      characteristics of SLPs who are early adopters of HRM are unclear; perspectives
      of early adopters may shape how the technology is received by the field at large.
      We hypothesized that younger SLPs, those working in outpatient settings, those
      with a strong knowledge base in HRM, and those with experience in other types of
      instrumentation are more likely to have interest in adopting HRM. We surveyed the
      population of board-certified SLPs (BCS-S; n = 262) with a 33% response rate (n =
      78). Firth logistic regression was used to determine differences in those
      expressing interest in adopting HRM into future practice (n = 28) and those who
      did not (n = 45) from the analytic sample of 73 respondents. The best fitting
      model predicted that SLPs: (1) with training in more types of instrumentation;
      and (2) believing they could explain the HRM procedure to a patient were more
      likely to plan to adopt pharyngeal HRM into regular clinical practice. Experience
      with a variety of instrumentation techniques may encourage SLPs to use new forms
      of technology. Knowledge of early adopter demographics will allow for development
      of targeted trainings and determination of HRM implementation barriers.
      Identification of a clinician sub-group more likely to adopt other new
      technologies in the future may also be possible.

PMID- 30232551
TI  - Facial nerve dysfunction after superficial parotidectomy with or without
      continuous intraoperative electromyographic neuromonitoring: a prospective
      randomized pilot study.
AB  - PURPOSE: There are no randomized trials comparing the incidence or severity of
      facial nerve dysfunction after superficial parotidectomy with or without
      continuous intraoperative electromyographic neuromonitoring. This pilot study
      aimed to assess the variability in outcomes to help determine the needs and
      possible ethical issues in a full-scale study. METHODS: Prospective randomized
      pilot study comparing the incidence and grade of facial nerve dysfunction among
      106 patients subjected to superficial parotidectomy with or without continuous
      four channels electromyographic neuromonitoring (52 monitored patients and 54
      controls). RESULTS: The incidences of immediate (38.3% vs. 51.8%, p = 0.1) and
      late facial dysfunction, up to 180 days following surgery, (3.8% vs. 5.5%, p =
      0.4) were similar between monitored patients and controls. Immediate facial nerve
      dysfunction with a House-Brackmann >= grade III was more frequent among the non
      monitored patients (57.8% vs. 30%, p = 0.2), and outcomes were significantly
      poorer in this group (mean sum score of 68.7 vs. 81.5, p = 0.002), when assessed
      with the regional Sunnybrook scale. A full-scale prospective randomized study to
      detect a significant reduction in the incidence of immediate facial nerve
      dysfunction with the use of continuous intraoperative electromyographic
      neuromonitoring, with 80% power and a 5% significant level, would require 560
      patients allocated to the monitored and control groups. Considering a mean rate
      of 30 patients/year/center, such a study would require the participation of five
      centers for 4 years. CONCLUSIONS: In the present pilot study, the incidences of
      immediate and late facial nerve dysfunction were similar between patients with
      benign parotid tumors subjected to superficial parotidectomy with or without
      continuous intraoperative electromyographic neuromonitoring. However, immediate
      facial dysfunction was more severe among the non-monitored patients.

PMID- 30232553
TI  - The necessity to use selective NADPH oxidase inhibitors.

PMID- 30232554
TI  - Treating benign ureteroenteric strictures: 27-year experience comparing
      endourological techniques with open surgical approach.
AB  - PURPOSE: To compare open surgical anastomotic revision with endourological
      techniques for the treatment of ureteroenteric strictures in patients with
      urinary diversions. METHODS: All records of patients treated for ureteroenteric
      strictures in our clinic between 1989 and 2016 were retrospectively reviewed. In
      76 patients, 161 completed procedures were analyzed: 26 open revisions vs. 135
      endourological treatments, including balloon dilation, Wallstent and/or laser
      vaporization. RESULTS: Median follow-up was 34 months. At 60 months, patency
      rates were 69% (95% CI 52-92%) after open vs. 27% (95% CI 19-39%) after endo
      treatment (p = 0.003); median patency duration was 15.5 vs. 5 months,
      respectively (p = 0.014). Eventually, 15% of patients required open surgery after
      primary endo-treatment and 21% received endoscopic re-treatment after primary
      open surgery. Cox regression analysis revealed no confounding factors among the
      risk factors added to the model. Complication rates were higher after open
      surgery (27% Clavien 2, 12% Clavien 3-4 vs. 5% Clavien 1-2, 3% Clavien 3, p =
      0.528). Median postoperative hospital stay was 14 days (open) vs. 2 days (endo),
      p < 0.001. Mean estimated glomerular filtration rate improved with + 17 (open)
      vs. + 8.1 (endo), p = 0.024. Renal function was compromised in 8% of patients in
      the open surgery group vs. 6% in the endo-treatment group. CONCLUSIONS: In these
      patients, in terms of patency and patency duration, open surgery was superior to
      endourology. Nevertheless, endourological treatments offer a safe and less
      invasive alternative to delay or avoid open surgery, especially in patients who
      are unfit for open surgery.

PMID- 30232552
TI  - Propranolol inhibits the activity of PI3K, AKT, and HIF-1alpha in infantile
      hemangiomas.
AB  - PURPOSE: We sought to evaluate effect of propranolol in the treatment of
      infantile hemangiomas by quantifying the amount of phosphatidylinositol 3-kinase
      (PI3K), protein kinase B (AKT), and hypoxia-inducible factor-1alpha (HIF-1alpha).
      METHODS: Hemangioma tissue was isolated from an infant patient and implanted into
      nude mice to establish a hemangioma model. Twenty-four hemangioma-model nude mice
      were divided into two groups including a control group (saline, by gastrogavage)
      and an experimental group (propranolol, by gastrogavage). The hemangioma-model
      nude mice were euthanized and tumors were removed at 30 and 50 days (before and
      after treatment). HE staining was used to observe the histopathological changes,
      and western blot and quantitative real-time PCR were used to describe levels of
      protein and mRNA expression of PI3K, AKT, and HIF-1alpha. RESULTS: Propranolol
      treatment decreased tumor size as compared to the control group. Protein and mRNA
      expression levels of PI3K, AKT, and HIF-1alpha were lower in the experimental
      group at day 50 compared to the control group at day 50 and the experimental
      group at day 30 (p < 0.05). CONCLUSION: Propranolol can promote regression of
      infantile hemangiomas, which may be related to the inhibition of PI3K, AKT, and
      HIF-1alpha activity.

PMID- 30232555
TI  - The Super-High SMAS Facelift Technique with Tailor Tack Plication.
AB  - BACKGROUND: Super-high superficial musculoaponeurotic system (SMAS) suspension
      and tailor tack plication are powerful facelift tools used in cases of primary
      facial rhytidectomy. TECHNIQUE: Thorough pre-operative patient screening and
      counseling are completed in an outpatient cosmetic surgery center. A super-high
      SMAS flap is developed by undermining and incising along a line extending from
      the tragus to lateral canthus and dissecting the SMAS sufficiently to induce
      movement of the lateral nose and the oral commissure with traction on the SMAS.
      The SMAS is suspended from the deep temporal fascia using 4-0 Mersilene sutures.
      Tailor tack sutures are placed strategically in the SMAS caudal to the malar bone
      to eliminate any residual laxity in the SMAS close to the oral commissures and
      the cheek area. This is repeated until the laxity of the SMAS is completely
      eliminated. The orbicularis muscle is conservatively suspended laterally from the
      deep temporal fascia, facial volume is restored with fat grafting, the neck is
      contoured, if necessary, and the vest-over-pants platysma overlap technique is
      commonly utilized. Concomitant forehead rejuvenation, blepharoplasty, and laser
      resurfacing are extremely common. RESULTS: Of the 72 cases of primary
      rhytidectomy performed by the senior author on consecutive patients included in
      the study, there were 64 (89%) female and 8 (11%) male patients. The average age
      of the patient at the time of primary facelift was 58 years old. Fifteen out of
      72 (21%) patients received one dose of desmopressin (DDAVP) injection during the
      surgery, and one patient received DDAVP the day after surgery to maintain
      hemostasis. There was no incidence of facial nerve injury. Of those 72 cases, 3
      (4%) developed minor hematomas that were resolved by aspiration. There were no
      expanding hematomas that required surgery. Of the 26 patients whose satisfaction
      was documented, 24 were very satisfied. Two patients expressed their
      dissatisfaction with the results, and one of these patients underwent a revision
      operation by the senior author. The other patient was mainly not pleased with the
      recovery duration. CONCLUSION: An alteration in the SMAS elevation and suspension
      is described with strategic submalar plication, providing a powerful technique
      for primary facial rhytidectomy that offers reliable and significant malar lift,
      orbicularis suspension, improvement in jowls, and repositioning of the oral
      commissure. The technical details are demonstrated through complete video
      segments along with many nuances that make delivery of optimal and natural
      outcomes possible, while maintaining the normal anatomy. LEVEL OF EVIDENCE IV:
      This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 30232557
TI  - Correction to: The study of human Y chromosome variation through ancient DNA.
AB  - The following sentence on the 11th page of the article.

PMID- 30232558
TI  - Everolimus in patients with multiply relapsed or cisplatin refractory germ cell
      tumors: results of a phase II, single-arm, open-label multicenter trial (RADIT)
      of the German Testicular Cancer Study Group.
AB  - BACKGROUND: Treatment options for patients (pts) with multiply relapsed or
      refractory metastatic germ cell cancer (GCC) are limited. The mTOR inhibitor
      everolimus has been approved for the treatment of different solid tumors and was
      assessed in refractory GCC within this phase II RADIT trial of the German
      Testicular Cancer Study Group. METHODS: GCC pts progressing during cisplatin
      based salvage chemotherapy, or relapsing after high-dose chemotherapy, or failing
      at least two lines of cisplatin-based chemotherapy were eligible. Prior
      combination chemotherapy with gemcitabine, oxaliplatin and paclitaxel, or a
      doublet combination of these drugs was mandatory. Primary endpoint was the
      progression-free survival rate at 12 weeks. Twenty-five evaluable pts were
      needed, assuming a 20% two-sided type 1 error and 95% power to reject the null
      hypothesis of 5% of patients being progression-free after 12 weeks. At least one
      pt among the first 13 pts being progression-free after 6 weeks was mandatory to
      complete recruitment. Secondary endpoints were objective response rate, disease
      control rate (SD + PR + CR), median progression-free survival (PFS), median
      overall survival (OS), and safety. The trial was registered at
      http://clinicaltrials.gov as NCT01242631. RESULTS: Twenty-five pts from six
      German centers were treated with everolimus 10 mg orally once daily until disease
      progression or unacceptable toxicity between December 2010 and January 2014. 12
      week PFS rate was 0%, no objective responses were achieved, and only one pt had
      stable disease after 6 weeks on treatment as a prerequisite of completing patient
      accrual accounting for a 6-week disease control rate of 5.4%. Median PFS and OS
      were estimated at 7.4 weeks and 8.3 weeks, respectively. Toxicity was acceptable,
      with one treatment discontinuation due to adverse events, and no new safety
      signals detected. CONCLUSIONS: Targeting the mTOR pathway with single-agent
      everolimus failed to produce clinically relevant responses in pts with heavily
      pretreated and/or cisplatin-refractory GCC.

PMID- 30232559
TI  - Predicting Concussion Recovery in Children and Adolescents in the Emergency
      Department.
AB  - PURPOSE OF REVIEW: Concussion, or mild traumatic brain injury (mTBI), represents
      the majority of pediatric Emergency Department (ED) presentations of TBI. While
      most children and adolescents will recover within 4 weeks of injury,
      approximately one third will continue to experience persisting symptoms. This
      review aimed to provide an overview of literature from the past 5 years examining
      predictors of recovery in the ED. RECENT FINDINGS: Predictors could be
      characterized into three categories; (i) cognition, (ii) proteomics, and (iii)
      pre-injury/injury-related factors. There is preliminary support for the use of
      computerized neuropsychological testing. The prognostic use of proteomics is a
      promising area of future research. Pre-injury and injury-related characteristics
      have been thoroughly examined and developed into a clinical risk score for
      predicting delayed recovery. Substantial progress has been made in identifying
      risk factors for delayed recovery at ED presentation. The current evidence
      provides a platform for additional research that can refine and validate these
      predictors.

PMID- 30232560
TI  - Real-time reservoir operation using data mining techniques.
AB  - The optimal operation of hydropower reservoirs is essential for the planning and
      efficient management of water resources and the production of hydroelectric
      energy. Various techniques such as the genetic algorithm (GA), artificial neural
      networks (ANN), support vector machine (SVM), and dynamic programming (DP) have
      been employed to calculate reservoir operation rules. This paper implements the
      data mining techniques SVM and ANN to calculate the optimal release rule of
      hydropower reservoirs under "forecasting" and "non-forecasting" scenarios. The
      employment of data mining techniques accounting for data uncertainty to calculate
      optimal hydropower reservoir operation is novel in the field of water resource
      systems analysis. The optimal operation of the Karoon 3 reservoir, Iran, serves
      as a test of the proposed methodology. The upstream streamflow, storage records,
      and several lagged variables are model inputs. Data obtained from solving the
      reservoir optimization problem with nonlinear programming (NLP) are applied to
      train (calibrate) the SVM, and ANN, SVM, and ANN are executed in the "non
      forecasting" scenario based on all inputs along with their time-lagged variables.
      In contrast, current parameters are removed from the set of inputs in the
      "forecasting" scenario. The results of the SVM model are compared with those of
      the ANN model with the correlation coefficient (R), the mean error (ME), and the
      root mean square error (RMSE). This paper's results indicate performance of the
      SVM is better than that of the ANN model by 1.5%, 400%, and 10% with respect to
      the R, ME, and RMSE diagnostic statistics, respectively. In addition, SVM and ANN
      overcome data uncertainty ("forecasting" scenario) to produce optimal reservoir
      operation.

PMID- 30232561
TI  - Predictive utility of childhood diagnosis of ICD-10 hyperkinetic disorder: adult
      outcomes in the MTA and effect of comorbidity.
AB  - Diagnostic guidelines differ between DSM attention-deficit/hyperactivity disorder
      (ADHD) and ICD hyperkinetic disorder (HKD). Only 145 of 579 children age 7-9 in
      the Multimodal Treatment Study of ADHD (the MTA) with combined-type DSM-IV ADHD
      met criteria for ICD-10 HKD, because major internalizing comorbidities and more
      stringent symptom count/pervasiveness requirements excluded most. The 145 HKD had
      significantly better 14-month medication response than the rest. We explored
      whether HKD had greater adult symptom persistence and/or impairment than other
      ADHD. Multi-informant assessments were done for 16 years. We used the 12/14/16
      year assessments, in young adulthood. The post-attrition 109 with baseline HKD
      had no greater adult persistence of ADHD symptoms/impairment than 367 without
      HKD, but had more cumulative stimulant use, more job losses, lower emotional
      lability, and fewer car crashes. However, those excluded for internalizing
      comorbidity but otherwise meeting HKD criteria had significantly more
      persistence. Only 6 of the 109 (5.5%) with baseline HKD met ICD-10 criteria for
      HKD in adulthood, compared to 25 of 367 (6.8%) without a childhood HKD diagnosis.
      Despite greater initial symptom severity, HKD had no worse 16-year young adult
      outcome than others, except for job losses, balanced by less emotional lability
      and fewer crashes. Comorbid internalizing disorder seems to have worse prognosis
      than initial severity/pervasiveness of ADHD symptoms.

PMID- 30232563
TI  - Substrates specificity of tannase from Streptomyces sviceus and Lactobacillus
      plantarum.
AB  - Tannases can catalyze the hydrolysis of galloyl ester and depside bonds of
      hydrolysable tannins to release gallic acid and glucose, but tannases from
      different species have different substrate specificities. Our prior studies found
      that tannase from Lactobacillus plantarum (LP-tan) performed a higher esterase
      activity, while the tannase from Streptomyces sviceus (SS-tan) performed a higher
      depsidase activity; but the molecular mechanism is not elucidated. Based on the
      crystal structure of LP-tan and the amino acid sequences alignment between LP-tan
      and SS-tan, we found that the sandwich structure formed by Ile206-substrate
      Pro356 in LP-tan was replaced with Ile253-substrate-Gly384 in SS-tan, and the
      flap domain (amino acids: 225-247) formed in LP-tan was missed in SS-tan, while a
      flap-like domain (amino acids: 93-143) was found in SS-tan. In this study, we
      investigated the functional role of sandwich structure and the flap (flap-like)
      domain in the substrate specificity of tannase. Site-directed mutagenesis was
      used to disrupt the sandwich structure in LP-tan (P356G) and rebuilt it in SS-tan
      (G384P). The flap in LP-tan and the flap-like domain in SS-tan were deleted to
      construct the new variants. The activity assay results showed that the sandwich
      and the flap domain can help to catalytic the ester bonds, while the flap-like
      domain in SS-tan mainly worked on the depside bonds. Enzymatic characterization
      and kinetics data showed that the sandwich and the flap domain can help to
      catalytic the ester bonds, while the flap-like domain in SS-tan may worked on the
      depside bonds.

PMID- 30232562
TI  - Natural Products for Promoting Joint Health and Managing Osteoarthritis.
AB  - PURPOSE OF REVIEW: Osteoarthritis, the most common joint disease, is associated
      with substantial medical costs, lost productivity, and reduced quality of life.
      However, available pharmaceutical treatments have limitations in terms of
      efficacy and long-term safety. RECENT FINDINGS: In vitro evidence suggests that
      some natural products may possess anti-inflammatory and anti-oxidative properties
      and may inhibit the release of key osteoarthritis-related cytokines. There is,
      therefore, ongoing interest in identifying natural products that safely promote
      joint health and treat osteoarthritis. Numerous plant extracts, including
      curcumin, Boswellia extract, and pycnogenol, have shown effect sizes (ES) for
      reducing pain and functional disability larger than those observed with
      analgesics and products such as glucosamine and chondroitin. The ES for
      methylsulfonylmethane and avocado/soybean unsaponifiables are also considered to
      be clinically relevant. Data from a small number of studies using natural
      products for treating osteoarthritis are promising but require confirmation in
      further well-designed clinical trials.

PMID- 30232564
TI  - An epidemiological analysis of osteoporotic characteristics in patients affected
      with rheumatoid arthritis in Kazakhstan.
AB  - PURPOSE: We aimed to assess which of the major risk factors associated with
      rheumatoid arthritis (RA) severity are also associated with osteoporosis-related
      phenotypes (OP-RP) in the native population of Kazakhstan. METHODS: Four hundred
      six RA patients (90.6% females) with 397 controls-unaffected first-degree
      relatives were recruited. Biochemical factors were recorded, and OP-RP were
      assessed using QCT scans and ultrasound densitometry (US) of the forearm to
      estimate cortical indices (CI), spongial bone mineral density (BMDSPN), and US_T
      scores. RESULTS: In the RA affected female population, ~ 80% suffered from
      osteopenia or osteoporosis. All OP-RP were negatively correlated with age and
      female's sex, as expected, and thus accordingly adjusted, resulting in
      consistent, significantly [p = 0.016 (CI), p < 0.0001 (both BMDSPN and US_T
      scores)] lower OP-RP estimates in affected females. Using multiple regression
      analysis for OP-RP manifestations, only age and disease duration appeared
      consistently associated with all three studied phenotypes, while menopause status
      or years following the onset of menopause were also significant for BMDSPN and
      US_T-scores. However, when disease duration was examined, we found that it was
      significantly dependent on morning stiffness, ESR, total cholesterol levels,
      weight, and menopause status, which explains 38.6% of the disease duration.
      CONCLUSIONS: Approximately 80% of female RA patients suffer from osteoporosis or
      osteopenia in the study group, which appears from a young age. RA disease
      duration is the major risk factor for OP-RP deterioration, especially as assessed
      by BMDSPNG, and US_T-scores. As a result, all OP-RP demonstrate significantly
      lower levels in comparison to sex- and age-matched unaffected individuals.

PMID- 30232565
TI  - Rifampin and tobramycin combination with PMMA antibiotic cement.
AB  - Rifampin is a powerful antibiotic used in the treatment of biofilm-forming
      bacteria with studies supporting its use in PMMA cement. However, it has not been
      widely accepted for its use in PMMA cement due to a perception that it is unable
      to solidify in a timely manner. The technique described consists of ratio of
      aminoglycoside and rifampin that reduces time to solidification to approximately
      15-20 min.

PMID- 30232566
TI  - LARS versus hamstring tendon autograft in anterior cruciate ligament
      reconstruction: a single-centre, single surgeon retrospective study with 8 years
      of follow-up.
AB  - PURPOSE: The choice of graft type in the anterior cruciate ligament (ACL)
      reconstruction remains a subject of controversy. The aim of this study was to
      assess the outcomes in ACL reconstructions performed using a four-strand
      hamstring tendon graft (4SHG) or a LARS ligament comparing the effectiveness of
      the two grafts at a medium follow-up of 8 years. METHODS: This retrospective,
      single-centre, single surgeon study evaluated the clinical, functional and
      radiographic outcomes in 50 patients who underwent ACL reconstruction (25 4SHG
      and 25 LARS). Patients who underwent surgery after more than 6 months from injury
      and showed radiographically visible degenerative changes at time of surgery were
      excluded from the study. RESULTS: None of the patients underwent re-surgery in
      the same knee. The range of motion of the operated knee, compared to the
      contralateral, was good for both groups. The anterior drawer test resulted
      negative in 21 patients (84%) in the LARS group and eight patients (32%) in the
      4SHG group (P = 0.039). The Lachman test was negative in 19 patients (76%) in the
      LARS group and in 11 patients (44%) in the 4SHG group (P = 0.045). Although other
      results of ACL reconstruction measured by Lysholm scores, IKDC evaluation, Tegner
      scores and radiographic images showed using a LARS graft tended to be superior to
      using a 4SHG, there were no statistically significant differences calculated.
      CONCLUSION: Our results suggest that 4 years after ACL reconstruction using a
      LARS ligament or 4SHG dramatically improves the function outcome, while the
      patients in the LARS group displayed a higher knee stability than those in the
      4SHG group.

PMID- 30232568
TI  - Laparoscopy in Rwanda: A National Assessment of Utilization, Demands, and
      Perceived Challenges.
AB  - BACKGROUND: Laparoscopy has proven to be feasible and effective at reducing
      surgical morbidity and mortality in low resource settings. In Rwanda, the demand
      for and perceived challenges to laparoscopy use remain unclear. METHODS: A mixed
      methods study was performed at the four Rwandan national referral teaching
      hospitals. Retrospective logbook reviews (July 2014-June 2015) assessed procedure
      volume and staff involvement. Web-based surveys and semi-structured interviews
      investigated barriers to laparoscopy expansion. RESULTS: During the study period,
      209 laparoscopic procedures were completed: 57 (27.3%) general surgery cases; 152
      (72.7%) ob/gyn cases. The majority (58.9%, 125/209) occurred at the private
      hospital, which performed 82.6% of cholecystectomies laparoscopically (38/46).
      The three public hospitals, respectively, performed 25% (7/28), 15% (12/80), and
      0% (denominator indeterminate) of cholecystectomies laparoscopically. Notably,
      the two hospitals with the highest laparoscopy volume relied on a single surgeon
      for more than 85% of cases. The four ob/gyn departments performed between 4 and
      87 laparoscopic cases (mostly diagnostic). Survey respondents at all sites listed
      a dearth of trainers as the most significant barrier to performing laparoscopy
      (65.7%; 23/35). Other obstacles included limited access to training equipment and
      courses. Equipment and material costs, equipment functionality, and material
      supply were perceived as lesser barriers. Twenty-two interviews revealed
      widespread interest in laparoscopy, insufficient laparoscopy exposure, and a need
      for trainers. CONCLUSION: While many studies identify cost as the most
      prohibitive barrier to laparoscopy utilization in low resource settings, logbook
      review and workforce perception indicate that a paucity of trainers is currently
      the greatest obstacle in Rwanda.

PMID- 30232569
TI  - Outcomes of Adrenal Venous Sampling in Patients with Bilateral Adrenal Masses and
      ACTH-Independent Cushing's Syndrome.
AB  - BACKGROUND: Management of patients with bilateral adrenal masses and ACTH
      independent Cushing's syndrome (AICS) is challenging, as bilateral adrenalectomy
      can lead to steroid dependence and lifelong risk of adrenal crisis. Adrenal
      venous sampling (AVS) has been previously reported to facilitate lateralization
      for guiding adrenalectomy. The aim of the current study was to investigate the
      utility of AVS using protocol from study by Young et al. in the management of
      patients with bilateral adrenal masses and AICS. METHODS AND DESIGN: A
      retrospective review of all patients with bilateral adrenal masses and AICS who
      underwent AVS from 2008 to 2016 was performed. AVS for cortisol and epinephrine
      was performed with dexamethasone suppression. The adrenal vein to peripheral vein
      cortisol ratios and side-to-side cortisol lateralization ratios were calculated.
      RESULTS: AVS was successful in 8 of 9 patients. All 8 patients had AVS results
      indicating bilateral cortisol hypersecretion. Six patients underwent
      adrenalectomy: 3 had unilateral adrenalectomy of the larger size mass, 2 had
      bilateral adrenalectomy (both sides >4 cm.) and 1 had stepwise bilateral
      adrenalectomy. Final pathology revealed macronodular adrenal hyperplasia in all 6
      patients that underwent surgery. CONCLUSION: AVS was useful in excluding a
      unilateral adenoma as the source of AICS in this study of patients with bilateral
      adrenal masses and AICS. However, adrenal mass size influenced surgical decision
      making more than AVS results. More data are needed before AVS can be advocated as
      essential for management of patients with bilateral adrenal masses and AICS.

PMID- 30232567
TI  - Enteroviral Infections as a Trigger for Type 1 Diabetes.
AB  - PURPOSE OF REVIEW: To provide an overview of studies that have detected
      enteroviruses (EV) in samples from people with type 1 diabetes (T1D), the
      techniques they have used, and which challenges they have encountered. RECENT
      FINDINGS: Recent studies have detected EVs in serum, blood, stools, nasal swabs,
      and pancreas of people with T1D before or around clinical onset of disease,
      indicating that an association between EV infections and T1D exists. However,
      definitive evidence for its role as disease triggers is lacking. Recent access to
      human samples is starting to provide the necessary tools to define their role in
      disease pathogenesis. Emerging evidence suggests that chronic infections take
      place in the pancreas of diabetic donors. However, the development of sensitive
      techniques able to detect low amounts of viral protein and RNA still constitute a
      major challenge for the field. New evidence at the protein, RNA, and host immune
      response level suggests a role for EV infections in the development of
      autoimmunity. In the upcoming years, new technologies, collaborative efforts, and
      therapeutic interventions are likely to find a definitive answer for their role
      in disease pathogenesis.

PMID- 30232570
TI  - Shift Work and Heart Rate Variability Coherence: Pilot Study Among Nurses.
AB  - This study used ambient heart rate monitoring among health care workers to
      determine whether a novel measure of heart rate variability (HRV), as well as
      sleep disturbances, fatigue, or cognitive performance differed among non-rotating
      night shift nurses relative to those working permanent day shifts. Continuous
      ambulatory HRV monitoring was performed among night nurses (n = 11), and a
      comparison group of permanent day nurses (n = 7), over a 36-h period coinciding
      with the last two 12-h shifts of each participant's work week. Symptoms and
      psychomotor vigilance were assessed at the end of the ambient HRV monitoring
      period, and no differences between shifts were observed. Day nurses exhibited an
      increase in hourly mean HRV coherence ratios during their sleep period,
      suggesting a circadian pattern of cardiorespiratory phase coupling, whereas night
      nurses had no increase in HRV coherence ratios during their sleep period. The HRV
      coherence patterns were similar to high frequency HRV power among nurses on the
      same shift. To the authors knowledge, this study was the first to quantify
      patterns of the HRV coherence ratio among shiftworkers in a non-experimental
      (work/home) setting. The results suggest a pattern of autonomic dysregulation
      among night workers during their sleep period relative to those working day
      shifts. The HRV coherence ratio may serve as a novel indicator of HRV
      dysregulation among shift workers.

PMID- 30232571
TI  - First evidence of viable progeny from three interspecific parents in sturgeon.
AB  - Polyspermy is the most commonly observed cause of embryonic abnormalities in
      fertilization, often resulting in death. In sterlet (Acipenser ruthenus),
      however, polyspermic embryos have high survival (similar to a control group) and
      morphological development is similar to monospermic larvae. Ploidy of these
      individuals is n/2n mosaic (whereas the normal state for A. ruthenus is a
      functional diploid). This study was undertaken to test whether sturgeon eggs can
      be fertilized by several spermatozoa from different species to produce viable
      offspring from three interspecific parents: A. ruthenus (2n), A. gueldenstaedtii
      (4n), and A. baerii (4n). Four trials were performed: (1) and (2) A. baerii eggs
      were fertilized with a mixture of A. ruthenus and A. gueldenstaedtii sperm; (3)
      A. gueldenstaedtii eggs were fertilized with a mixture of A. baerii and A.
      ruthenus sperm; and (4) A. gueldenstaedtii eggs were fertilized with a mixture of
      A. gueldenstaedtii and A. ruthenus sperm. Fertilized embryos with abnormal
      cleavage (3, 5, 6, 7, 9, and 10 cells) were collected and kept separately until
      14 days post-fertilization. Ploidy level of 25 larvae (hatched from abnormal
      cleaved embryos) was evaluated by flow cytometry. Forty-four percent of observed
      hybrids had a mosaic 2n/3n ploidy. Five larva were processed further with
      microsatellite analysis and demonstrated that three specimens were heterospecific
      polyspermic larvae, containing alleles from three parents, and two specimens were
      conspesific polyspermic larvae from two parents. This astonishing phenomenon was
      emphasized by the fact that it was generated without any significant
      intervention.

PMID- 30232573
TI  - Phosphoglyceride crystal deposition disease in the abdominal wall: a case report.
AB  - BACKGROUND: Phosphoglyceride crystal deposition disease (PGDD) is characterized
      by phosphoglyceride crystal deposition that simulates neoplasia in soft tissue
      scars or bone. Reports of PGDDs are rare. Here, we present the case of a patient
      with PGDD in the abdominal wall. CASE PRESENTATION: A 57-year-old Japanese man
      with worsening right lower abdominal pain had no significant family or
      occupational history. Laboratory data showed elevated inflammatory markers with a
      white blood cell count of 14,400 * 109/L and C-reactive protein of 11.8 mg/L, but
      no other abnormalities. Helical computed tomography (CT) revealed a tumor in the
      abdominal wall (longest dimension, approximately 10 cm). Positron emission
      tomography-CT revealed fluorodeoxyglucose accumulation in the mass only (SUVmax,
      41). Clinical and radiographic findings suggested malignant lymphoma,
      undifferentiated sarcoma, or liposarcoma. He underwent exploratory laparotomy and
      further treatment. At surgery, we found a huge milky-whitish mass with a rough
      surface in the transversus abdominis. Complete resection was performed and his
      postoperative recovery was good. Surprisingly, the final pathologic diagnosis was
      phosphoglyceride crystal deposition disease with the characteristic crystal
      deposition in a corolla shape, histiocytic reaction with abundant foreign-body
      type giant cells, and no evidence of neoplasia. The patient remains asymptomatic
      with no disease recurrence. CONCLUSION: Although phosphoglyceride crystal
      deposition disease in the abdominal wall is rarely encountered in clinical
      practice, its inclusion in differential diagnosis is important. Given the
      occurrence at sites of invasive procedures, we believe efforts to reduce
      invasiveness when performing surgery and follow-up for early detection of
      recurrence are important.

PMID- 30232574
TI  - PGC1alpha regulates ACMSD expression through cooperation with HNF4alpha.
AB  - ACMSD is a tryptophan metabolic key enzyme. HNF4alpha regulates the transcription
      of some energy-metabolic enzymes by cooperating with PGC1alpha, a major
      transcriptional co-regulator involved in energy metabolism. In this study, we
      investigated the involvement of PGC1alpha in Acmsd expression through cooperation
      with HNF4alpha. Luciferase reporter assay was performed in NIH3T3 cells using a
      reporter vector containing HNF4alpha responsive elements in the Acmsd 5' upstream
      transcriptional regulatory region together with HNF4alpha and/or PGC1alpha
      expression vectors. The Acmsd luciferase reporter activity was greatly elevated
      by co-overexpression of HNF4alpha and PGC1alpha in NIH3T3 cells. Moreover, the
      expression level of Acmsd mRNA was significantly increased by co-overexpression
      of HNF4alpha and PGC1alpha in primary hepatocytes compared with expression of
      either HNF4alpha or PGC1alpha alone. These results indicate that PGC1alpha is
      involved in Acmsd expression through cooperation with HNF4alpha.

PMID- 30232575
TI  - Effects of Repeated Treatment with Midazolam in SHR and SLA16 Rat Strains in the
      Triple Test.
AB  - We exposed male and female rats of SHR (Spontaneously Hypertensive Rats) and
      SLA16 (SHR.LEW-Anxrr16) strains, in a non-drugged state, for five consecutive
      days to the Triple Test (experiment 1); or after repeated treatment with
      midazolam (MDZ), for four consecutive days. The fifth day was performed without
      treatment (experiment 2). The first experiment showed that males did not avoid
      and females increased the exploration of the open arms over the days. In
      experiment 2, SLA16 from both sexes approached more the open arms than SHR rats.
      The MDZ anxiolytic-like effect was sustained in both strains and sexes over the
      days. On the fifth day, SLA16 still approached more the open arms than SHR rats.
      Data suggest an absence of repeated-trial tolerance to MDZ anxiolytic-like
      effects. Testing the SHR and SLA16 strains, especially females, could be
      necessary for the future search for the genes and molecular pathways underlying
      anxiety/emotionality.

PMID- 30232572
TI  - Peptidoglycan in Mycobacteria: chemistry, biology and intervention.
AB  - Peptidoglycan, a major glycoconjugate in the mycobacterial cell envelope provides
      strength to resist osmotic stress and plays a pivotal role in maintaining the
      cellular morphology. Several unique growth stage specific structural alterations
      occur in its constituent monosaccharides and peptides that allow Mycobacterium to
      survive nutrient starvation and environmental stress. Here, we discuss the
      enzymes involved in its intricate biosynthesis that are novel targets for
      therapeutic intervention and provide an opportunity for potential antibiotic
      adjuvants. We also revisit the enzymatic steps which are critical for maintaining
      the equilibrium between peptidoglycan synthesis and hydrolysis during cellular
      growth and division specifically focused on the importance of cell wall
      remodelling during "exit from dormancy" in Mycobacterium, a phenomenon with
      tremendous physiological and therapeutic importance for intervention in
      mycobacterial infections.

PMID- 30232577
TI  - A contemporary review of male breast cancer: current evidence and unanswered
      questions.
AB  - Male breast cancer is rare, accounting for 1% of all breast cancer diagnoses in
      the USA. Because of its rarity, most major breast cancer trials have included
      only female patients. This has resulted in limited prospective data to guide the
      clinical management of men with breast cancer. As a result, treatment decisions
      are typically extrapolated from data generated in female patients. This approach
      may be suboptimal, particularly considering the differing hormonal milieus
      between men and women with respect to both breast cancer development and
      treatment. Herein, we summarize current knowledge of the biology and
      clinicopathology of male breast cancer and review current approaches to
      locoregional and systemic management of this rare disease.

PMID- 30232579
TI  - eHealth for Stigma Reduction Efforts Designed to Improve Engagement in Care for
      People Living with HIV.
AB  - PURPOSE OF REVIEW: HIV-related stigma remains a significant barrier to engagement
      in care for persons living with HIV (PLWH) worldwide. This review examines the
      use of eHealth technologies for reducing stigma as a pathway toward improved
      engagement in care for PLWH. We provide a brief overview of effective stigma
      reduction interventions for PLWH, both eHealth and others; identify gaps in the
      research on use of eHealth technologies for stigma reduction; and suggest
      potential research avenues moving forward. RECENT FINDINGS: The majority of HIV
      related eHealth studies use technology to improve ART adherence. To date, few HIV
      related eHealth studies have included any measurement of stigma. Given the
      current narrow evidence base, further research is needed to determine whether
      eHealth technologies can help to reduce stigma and improve engagement in care for
      PLWH.

PMID- 30232578
TI  - Actionable Adherence Monitoring: Technological Methods to Monitor and Support
      Adherence to Antiretroviral Therapy.
AB  - PURPOSE OF REVIEW: Current digital technologies are being used for "actionable
      adherence monitoring"; that is, technologies that can be used to identify
      episodes of non-adherence to ART in a timely manner such that tailored
      interventions based on adherence data can be provided when and where they are
      needed most. RECENT FINDINGS: Current digital communication technologies used to
      monitor ART adherence include electronic adherence monitors (EAMs), digital
      ingestion monitors, cellular phones, and electronic pharmacy refill tracking
      systems. Currently available real-time adherence monitoring approaches based on
      cellular technology allow for the delivery of interventions precisely when and
      where they are needed. Such technology can potentially enable significant
      efficiency of care delivery and impact on adherence and associated clinical
      outcomes. Standard digital advances, such as automated reminders in EAM and
      electronic pharmacy records, may also achieve improvements with relatively lower
      cost and easier implementation. Future research is needed to improve the
      functionality of these approaches, with attention paid to system-level issues
      through implementation science, as well as acceptability and ethical
      considerations at the individual level.

PMID- 30232581
TI  - Is there a role for HIPEC in ovarian cancer?
AB  - Hyperthermic intraperitoneal chemotherapy (HIPEC) is promoted by some as a
      standard treatment for peritoneal carcinomatosis of epithelial ovarian cancer
      (EOC) and other tumor entities, despite lack of robust data supporting this.
      Publicly available evidence addressing the value of HIPEC in EOC is rather
      inconclusive, revealing contradictory and inconsistent results while some studies
      even report harm to the patients from a higher morbidity. On this ground, we
      cannot recommend the implementation and use of HIPEC outside of a randomized
      clinical trial setting.

PMID- 30232580
TI  - Factors affecting the live-birth rate in women with diminished ovarian reserve
      undergoing IVF-ET.
AB  - PURPOSE: The occurrence of diminished ovarian reserve (DOR) in women was growing
      in recent years. Although in vitro fertilization and embryo transfer (IVF-ET)
      became an effective treatment for DOR, the live-birth (LB) rate remains
      unsatisfactory. This study aimed to investigate the impact factors of LB rate in
      women with DOR undergoing assisted reproduction. METHODS: This was a single
      center retrospective cohort study. A total of 2277 IVF-ET or ICSI cycles from
      1957 DOR women were analysed. Impact factors of LB rate were explored via
      Student's t test, Pearson's Chi-square test, and multivariate logistic regression
      models. RESULTS: There were statistically significant differences in maternal age
      (P < 0.001), duration of infertility (P < 0.001), female body mass index (P =
      0.039), first IVF cycle (P = 0.004), poor ovarian response (P < 0.001), paternal
      age (P < 0.001), total gonadotropin dose (P = 0.010), endometrial thickness (P =
      0.021), number of follicles >= 14 mm (P = 0.007), number of oocytes retrieved (P
      < 0.001), number of frozen embryos (P = 0.014), and the stage (P < 0.001) and
      number (P < 0.001) of embryos transferred between the non-live-birth (NLB) and LB
      groups. However, only factors of maternal age, the stage and number of embryos
      transferred remained different after adjusting for potential confounders.
      CONCLUSIONS: Maternal age, the stage and number of embryos transferred were
      independent impact factors affecting the live-birth rate in women with DOR
      seeking for assisted conception.

PMID- 30232582
TI  - Laryngo fiberscopy-guided suspension procedure for an ectopic lingual thyroid
      obstructing airway.
AB  - BACKGROUND: Currently, there is no consensus regarding the optimal therapeutic
      strategy for the management of an ectopic lingual thyroid. A surgical approach is
      suggested when airway obstructive symptoms cannot be tolerated at all, or when
      bleeding or malignancy occurs. However, for patients in whom ectopic thyroid is
      the only functioning thyroid tissue, complete surgical excision needs to be
      followed by lifelong hormone replacement therapy. We report the case of an infant
      with ectopic lingual thyroid obstructing the airway that was treated using our
      novel surgical procedure. CASE PRESENTATION: A 10-day-old male infant presented
      with symptoms of airway obstruction and subclinical hypothyroidism. Imaging tests
      revealed an ectopic lingual thyroid and the absence of a normal pretracheal
      thyroid gland. We administered oral levothyroxine to lower his thyroid
      stimulating hormone (TSH) level and reduce the volume of the lingual mass;
      however, his airway symptoms did not improve. Subsequently, we performed a
      surgical intervention when he was 2 months old. We split the hyoid bone, and then
      suspended the lingual thyroid by suturing it to the hyoid bone to elevate the
      epiglottis. We confirmed the degree of suspension using intraoperative laryngo
      fiberscopy. After the surgery, the symptoms of airway obstruction were resolved
      and the patient was clinically euthyroid on low-dose oral levothyroxine.
      CONCLUSIONS: Our laryngo fiberscopy-guided suspension procedure can be an
      effective surgical procedure for the treatment of ectopic thyroid. This
      relatively simple surgical procedure could completely preserve the patient's
      thyroid tissue and resolve airway obstruction.

PMID- 30232583
TI  - "Reproducible" Research in Mathematical Sciences Requires Changes in our Peer
      Review Culture and Modernization of our Current Publication Approach.
AB  - The nature of scientific research in mathematical and computational biology
      allows editors and reviewers to evaluate the findings of a scientific paper.
      Replication of a research study should be the minimum standard for judging its
      scientific claims and considering it for publication. This requires changes in
      the current peer review practice and a strict adoption of a replication policy
      similar to those adopted in experimental fields such as organic synthesis. In the
      future, the culture of replication can be easily adopted by publishing papers
      through dynamic computational notebooks combining formatted text, equations,
      computer algebra and computer code.

PMID- 30232584
TI  - Post-marketing surveillance of gadobutrol for contrast-enhanced magnetic
      resonance imaging in Japan.
AB  - PURPOSE: To evaluate the safety of gadobutrol for magnetic resonance imaging in a
      prospective, non-interventional, post-marketing surveillance in Japan. MATERIALS
      AND METHODS: Gadobutrol was administered in accordance with Japanese prescribing
      information over a 2-year enrollment period, using a standardized questionnaire
      to collect information. The primary outcome was the incidence of adverse
      reactions (ARs) following gadobutrol injection. RESULTS: Questionnaire data were
      analyzed for 3337 patients (age, 58.1 +/- 17.4 years [mean+/-SD]). Gadobutrol was
      administered at a dose of 0.10 +/- 0.02 mL/kg body weight. Thirty-three patients
      were observed to have 42 ARs suspected to be due to gadobutrol, an incidence
      proportion of 0.99%; 29 ARs were acute (<1 h post-injection)-including one case
      of severe acute AR (0.03%). Patient subpopulations (with hepatic, renal,
      cardiovascular diseases) did not differ markedly in AR proportions categorized by
      age, sex, presence of comorbidity, or imaging indication. No cases of nephrogenic
      systemic fibrosis were reported. Investigators rated images as improved or
      profoundly improved following gadobutrol injection in 91.1% of examinations.
      CONCLUSION: Gadobutrol was well tolerated with a good safety profile in this post
      marketing surveillance of a large patient population in Japan.

PMID- 30232585
TI  - Artificial intelligence using neural network architecture for radiology (AINNAR):
      classification of MR imaging sequences.
AB  - PURPOSE: The confusion of MRI sequence names could be solved if MR images were
      automatically identified after image data acquisition. We revealed the ability of
      deep learning to classify head MRI sequences. MATERIALS AND METHODS: Seventy
      eight patients with mild cognitive impairment (MCI) having apparently normal head
      MR images and 78 intracranial hemorrhage (ICH) patients with morphologically
      deformed head MR images were enrolled. Six imaging protocols were selected to be
      performed: T2-weighted imaging, fluid attenuated inversion recovery imaging, T2
      star-weighted imaging, diffusion-weighted imaging, apparent diffusion coefficient
      mapping, and source images of time-of-flight magnetic resonance angiography. The
      proximal first image slices and middle image slices having ambiguous and
      distinctive contrast patterns, respectively, were classified by two deep learning
      imaging classifiers, AlexNet and GoogLeNet. RESULTS: AlexNet had accuracies of
      73.3%, 73.6%, 73.1%, and 60.7% in the middle slices of MCI group, middle slices
      of ICH group, first slices of MCI group, and first slices of ICH group, while
      GoogLeNet had accuracies of 100%, 98.1%, 93.1%, and 94.8%, respectively. AlexNet
      significantly had lower classification ability than GoogLeNet for all datasets.
      CONCLUSIONS: GoogLeNet could judge the types of head MRI sequences with a small
      amount of training data, irrespective of morphological or contrast conditions.

PMID- 30232586
TI  - Micro-Finite Element Analysis of the Proximal Femur on the Basis of High
      Resolution Magnetic Resonance Images.
AB  - PURPOSE OF REVIEW: Hip fractures have catastrophic consequences. The purpose of
      this article is to review recent developments in high-resolution magnetic
      resonance imaging (MRI)-guided finite element analysis (FEA) of the hip as a
      means to determine subject-specific bone strength. RECENT FINDINGS: Despite the
      ability of DXA to predict hip fracture, the majority of fractures occur in
      patients who do not have BMD T scores less than - 2.5. Therefore, without other
      detection methods, these individuals go undetected and untreated. Of methods
      available to image the hip, MRI is currently the only one capable of depicting
      bone microstructure in vivo. Availability of microstructural MRI allows
      generation of patient-specific micro-finite element models that can be used to
      simulate real-life loading conditions and determine bone strength. MRI-based FEA
      enables radiation-free approach to assess hip fracture strength. With further
      validation, this technique could become a potential clinical tool in managing hip
      fracture risk.

PMID- 30232587
TI  - Impact of a health information technology tool addressing information needs of
      caregivers of adult and pediatric hematopoietic stem cell transplantation
      patients.
AB  - PURPOSE: We developed BMT Roadmap, a health information technology (HIT)
      application on a tablet, to address caregivers' unmet needs with patient-specific
      information from the electronic health record. We conducted a preliminary
      feasibility study of BMT Roadmap in caregivers of adult and pediatric HSCT
      patients. The study was registered on ClinicalTrials.gov (NCT03161665;
      NCT02409121). METHODS: BMT Roadmap was delivered to 39 caregivers of adult and
      pediatric patients undergoing first-time HSCT at a single study site. We assessed
      person-reported outcome measures (PROMs) at baseline (hospital admission),
      discharge, and day 100: usefulness of BMT Roadmap (Perceived Usefulness);
      activation (Patient Activation Measure-Caregiver version [PAM-C]); mental health
      ([POMS-2(r)]: depression, distress, vigor, and fatigue); anxiety (State-Trait
      Anxiety Inventory); and quality of life (Caregiver Quality of Life Index-Cancer
      [CQOLC]). To identify determinants of caregiver activation and quality of life,
      we used linear mixed models. RESULTS: BMT Roadmap was perceived useful and
      activation increased from baseline to discharge (p = 0.001). Further, burden
      decreased through discharge (p = 0.007). Overall, a pattern of increasing vigor
      and decreasing depression, distress, fatigue, and anxiety was apparent from
      baseline to discharge. However, overall quality of life lowered at discharge
      after accounting for BMT Roadmap use, depression, anxiety, and fatigue (p =
      0.04). CONCLUSIONS: BMT Roadmap was a feasible HIT intervention to implement in
      HSCT caregivers. BMT Roadmap was associated with increased activation and
      decreased burden, but quality of life lowered across hospitalization. Findings
      support the need to further develop caregiver-specific self-directed resources
      and provide them both inpatient and outpatient across the HSCT trajectory.

PMID- 30232588
TI  - Tyrosinase and nestin immunohistochemical expression in melanocytic nevi as a
      histopathologic pattern to trace melanocyte differentiation and nevogenesis.
AB  - While histological analysis represents a powerful tool for the classification of
      melanocytic lesions as benign or malignant, a clear-cut distinction between a
      nevus and a melanoma is sometimes a challenging step of the diagnostic process.
      The immunohistochemical detection of tyrosinase, cardinal melanogenic enzyme
      during melanocytic maturation, has often been helpful in formulating a
      differential diagnosis due to the peculiar staining pattern in nevocytes compared
      with melanoma cells. Tyrosinase distribution in nevi appears to overlap with the
      cytoarchitectural changes observable within these lesions, that result in
      epidermal or superficial dermal nevocytes being larger and strongly expressing
      melanocytic differentiation antigens, such as tyrosinase, compared with deeper
      dermal nevus cells. Our study aimed to evaluate the immunohistochemical
      expression pattern of tyrosinase in different histological types of acquired
      dysplastic melanocytic nevi, including junctional, compound, and intradermal
      nevi. Moreover, to estimate whether in nevocytes the expression of tyrosinase was
      associated with their differentiation state, we investigated the expression of
      two recognized markers of pluripotency, CD34 and nestin. In all examined nevi,
      our analysis revealed a remarkable immunoreactivity for tyrosinase in junctional
      and superficial dermal nevocytes and a decreasing gradient of staining in dermal
      nevocytes, up to become negative in deeper dermis. Meanwhile, junctional and
      dermal nevocytes were lacking in CD34 protein. Furthermore, nestin immunostaining
      showed an opposite distribution compared with tyrosinase, leading us to look into
      the tyrosinase/nestin expression pattern in melanocytic nevus as a tool to better
      understand the final stages of differentiation of melanocyte precursors toward
      their ultimate anatomical site into the epidermis.

PMID- 30232590
TI  - A comparison between the feeding practices of parents and grandparents.
AB  - The aim of this study is to evaluate and compare mothers' and grandparents'
      feeding behaviours, the differences between the behaviours, the relationship
      between children's feeding problems and grandparents' feeding behaviours, as well
      as the relationship between grandparents' feeding behaviour and children's body
      mass index (BMI). This study prompts physicians to pay attention to the on
      feeding behaviours of grandmothers when evaluating the feeding problems and
      behaviours of children. This study is a controlled case study. Two hundred
      children (between 2 and 5 years of age) were included. Amongst these children,
      150 of them were only fed by their mothers and 50 of them were fed by both their
      mother and grandmother. The feeding behaviour was evaluated by the Comprehensive
      Feeding Practices Questionnaire (CFPQ).Three domains emerged in this study: Some
      of the feeding behaviours were significantly different between the mothers and
      grandmothers who were questioned in the CFPQ. The feeding behaviours are related
      to the feeding problems; in this study, we show that, in some cases, whether some
      feeding behaviours were applied either more or less had a significant influence
      on feeding problems. There were positive correlations between the feeding
      behaviours of mothers and grandmothers. Conclusion: There is limited research
      about grandmothers' influence on child feeding. Research in grandmothers' feeding
      behaviours may reveal key concerns in children feeding problems and in preventing
      childhood obesity. What is Known: * According to studies, there are differences
      between the feeding behaviours of mothers and grandmothers. What is New: * This
      study is the first to explore the relationship between the feeding problems and
      feeding behaviours of both mothers and grandmothers. Also, a comparison of the
      mothers' and fathers' mothers' feeding behaviours has not yet been carried out.

PMID- 30232589
TI  - Association between radiation-induced cell death and clinically relevant
      radioresistance.
AB  - Radiotherapy (RT) is one of the major modalities for the treatment of human
      cancer and has been established as an excellent local treatment for malignant
      tumors. However, the existence of radioresistant cells remains one of the most
      critical obstacles in RT. To know the characteristics of radioresistant cells,
      clinically relevant radioresistant (CRR) cell lines were established. CRR cells
      can continue to proliferate in vitro and in vivo after exposure to 2 Gy/day of X
      rays for more than 30 days. Daily microscopic observation of the irradiated CRR
      cells has indicated that the increase in cell death is not observed within 7 days
      of irradiation with 10 Gy of X-rays, suggesting that cell death is involved in
      cellular radioresistance. Radiation-induced regulated cell death (RCD) can be
      classified into three categories: apoptosis, autophagy-dependent cell death and
      necrosis (necroptosis). This review focuses on an aspect of radiation-induced RCD
      that has often been neglected: the manner in which the cells are destroyed. In
      many studies, apoptosis is considered the primary mode of RCD in irradiated
      cancer cells; however, it is necessary to consider necrosis or necroptosis as one
      of the modes of radiation-induced RCD.

PMID- 30232591
TI  - Changes in bilirubin in infants with hypoxic-ischemic encephalopathy.
AB  - Antioxidant properties of bilirubin have been reported in many studies. We
      hypothesized that bilirubin might be involved in neuroprotection mechanisms
      against oxidative stress in infants with hypoxic-ischemic encephalopathy (HIE)
      and that total serum bilirubin (TSB) might increase in these patients. We
      retrospectively studied infants with gestational age >= 35 weeks and birth weight
      >= 1800 g who were admitted to the neonatal intensive care unit (NICU) with a
      diagnosis of moderate-to-severe HIE and received or did not receive therapeutic
      hypothermia. We evaluated peak TSB and changes of mean TSB in these patients in
      comparison with a control group of infants admitted to the NICU with diagnoses
      other than HIE. Peak and mean TSB values were lower in the no hypothermia and
      hypothermia groups in comparison with the control group, while differences were
      not noted between infants who received hypothermia or did not. Regression
      analysis showed that HIE and hypothermia significantly reduced the risk of
      developing TSB values higher than median value (> 8.4 mg/dL) in our
      population.Conclusion: Peak and mean TSB values were lower in infants with
      moderate-to-severe HIE than in control infants. HIE and hypothermia independently
      decreased TSB. These results exclude a TSB increase as a neuroprotective
      mechanism in infants with HIE. We speculated that low TSB values in infants with
      HIE could be due to hypoxic repression of HO expression and represent a defensive
      strategy for limiting brain injuries in these patients. What is Known: * The role
      of oxidative stress in the pathophysiology of hypoxic-ischemic encephalopathy
      (HIE) has been elucidated in many studies, and other studies have demonstrated
      the antioxidant properties of bilirubin. * The potential neuroprotective role of
      bilirubin as antioxidant agent has never been evaluated in infants with HIE. What
      is New: * Mean total serum bilirubin (TSB) values are lower in infants with
      moderate-to-severe HIE than in control infants, since HIE and hypothermia
      independently decreased TSB. * An increase in bilirubin was not a neuroprotective
      mechanism in infants with HIE possibly because of hypoxic repression of HO
      expression as defensive strategy for limiting brain injuries.

PMID- 30232592
TI  - Does lower extremity pain precede spinal pain? A longitudinal study.
AB  - The main objective was to investigate whether children aged 9-15 years at
      baseline were more likely to experience an incident event of spinal pain after
      experiencing lower extremity pain. Children's musculoskeletal pain was monitored
      by weekly mobile phone text message responses from parents, indicating whether
      the child had spinal pain, lower extremity pain, or upper extremity pain the
      preceding week. Data were analyzed using mixed effect logistic regression models
      and cox regression models. The association between an incident event of spinal
      pain and LE pain the preceding weeks increased with increasing observation period
      and was statistically significant for 12 and 20 weeks (OR = 1.34 (95% CI 1.05 to
      1.70) and OR = 1.39 (95% CI 1.11 to 1.75), respectively). We found that the
      likelihood increased in children with more frequent or longer duration of lower
      extremity pain. The reversed relationship was investigated as well, and we also
      found a positive association between spinal pain and a subsequent incidence event
      of lower extremity pain, but less pronounced.Conclusion: Children were more
      likely to experience an incident event of spinal pain after experiencing lower
      extremity pain. The likelihood increased in children with more frequent or longer
      duration of lower extremity pain. What is Known: * Both spinal pain and lower
      extremity pain often start early in life and is common already in adolescence.
      What is New: * Children were more likely to experience an incident event of
      spinal pain after experiencing LE pain. * The likelihood increased in children
      with more frequent or longer duration of LE pain.

PMID- 30232595
TI  - Guided evaluation and standardisation of mesenchymal stem cell culture conditions
      to generate conditioned medium favourable to cardiac c-kit cell growth.
AB  - Mesenchymal stem cells (MSCs) are known to secrete cardioprotective paracrine
      factors that can potentially activate endogenous cardiac c-kit cells (CCs). This
      study aims to optimise MSC growth conditions and medium formulation for
      generating the conditioned medium (CdM) to facilitate CC growth and expansion in
      vitro. The quality of MSC-CdM after optimisation of seeding density during MSC
      stabilisation and medium formulation used during MSC stimulation including
      glucose, ascorbic acid, serum and oxygen levels and the effects of treatment
      concentration and repeated CdM harvesting were assessed based on CC viability in
      vitro under growth factor- and serum-deprived condition. Our data showed that
      functional CdM can be produced from MSCs with a density of 20,000 cells/cm2,
      which were stimulated using high glucose (25 mM), ascorbic acid supplemented,
      serum-free medium under normoxic condition. The generated CdM, when applied to
      growth factor- and serum-deprived medium at 1:1 ratio, improved CC viability,
      migration and proliferation in vitro. Such an effect could further be augmented
      by generating CdM concentrates without compromising CC gene and protein
      expressions, while retaining its capability to undergo differentiation to form
      endothelial, smooth muscle and cardiomyocytes. Nevertheless, CdM could not be
      repeatedly harvested from the same MSC culture, as the protein content and its
      effect on CC viability deteriorated after the first harvest. In conclusion, this
      study provides a proof-of-concept strategy to standardise the production of CdM
      from MSCs based on rapid, stepwise assessment of CC viability, thus enabling
      production of CdM favourable to CC growth for in vitro or clinical applications.

PMID- 30232593
TI  - Psychosocial functioning of parents of children with heart disease-describing the
      landscape.
AB  - The aim was to describe the psychological functioning of parents of school-age
      children with heart disease (HD) in a large-scale, transnational evaluation of
      parent dyads across the spectrum of cardiac diagnoses and a range of psychosocial
      domains. Parents of children with HD attending routine out-patient cardiology
      follow-up visits completed questionnaires assessing their mental health, coping,
      and family functioning. Parents (1197 mothers and 1053 fathers) of 1214 children
      (mean age: 12.6 years; S.D. 3.0 years; median time since last surgery: 8.9 years)
      with congenital or acquired HD from three centers each in the UK and the USA
      participated (80% response rate). Parents of children with milder HD demonstrated
      few differences from healthy norms and had significantly lower scores on measures
      of illness-related stress and post-traumatic stress than parents of children with
      single ventricle conditions or cardiomyopathy. Parents in these latter two
      diagnostic sub-groups had significantly higher levels of anxiety and depression
      than healthy norms but did not differ on other measures of family functioning and
      coping skills. There were few differences between parents from the UK and the
      USA. Agreement between mothers and fathers within a dyad was highest for the
      measure of frequency of illness-related stressors (ICC = 0.67) and lowest for
      anxiety (ICC = 0.12).Conclusion: Our results suggest two different pathways for
      the long-term psychological well-being of parents of children with HD: on the one
      hand, more complex HD is associated with poorer long-term psychosocial outcomes;
      in contrast, there are also grounds for optimism, particularly for parents of
      children with less complex conditions, with better psychological outcomes noted
      for some groups of parents compared to previously reported early psychosocial
      outcomes. Future work needs to identify factors other than disease severity which
      might explain poorer (or better) functioning in some parents of children with
      more complex HD. What is Known: * Parents of children with congenital heart
      disease report elevated levels of anxiety, depression, and stress after cardiac
      surgery in infancy. * Maternal mental health problems can have an adverse impact
      on the psychological adjustment of the child with congenital heart disease. What
      is New: * Parents of children with milder forms of heart disease do not differ
      from healthy norms in the longer term and psychological outcomes are better than
      might be expected from early findings. * More complex diagnoses, particularly
      functional single ventricle conditions and cardiomyopathy, are associated with
      poorer long-term psychosocial outcomes for parents.

PMID- 30232594
TI  - Transient neonatal hyperinsulinaemic hypoglycaemia: perinatal predictors of
      length and cost of stay.
AB  - Admission to neonatal care causes separation of infants from their parents, can
      adversely affect breast-feeding and is associated with painful procedures. Our
      aim was to identify perinatal factors and cost of care associated with transient
      neonatal hyperinsulinaemic hypoglycaemia (HH). Infants born after 35 weeks of
      gestation admitted because of hypoglycaemia were studied. The neonates were
      divided into two groups (HH and non-HH), and their length and cost of care were
      compared and perinatal factors predicting those outcomes explored. Forty of the
      474 infants admitted with hypoglycaemia were diagnosed with HH. The HH group had
      a lower median (IQR) glucose level on admission compared to the non-HH group (p <
      0.001). The median (IQR) cost of stay was higher in the HH group (p < 0.001). In
      the HH group, the GIRmax was significantly correlated with cost of stay (p <
      0.001). GIRmax predicted a cost of stay > L9140 with an area under the ROC curve
      of 0.956. GIRmax > 13.9 mg/kg/min predicted admission cost > L9140 with 86%
      sensitivity and 93% specificity.Conclusion: Transient neonatal HH was associated
      with a higher length and cost of stay in infants admitted for hypoglycaemia. The
      GIRmax can predict the length and cost of stay. What is Known: * Neonatal
      hypoglycaemia is the leading cause of term and late preterm neonatal admissions.
      * Hyperinsulinism (HH) is the commonest cause of persistent hypoglycaemia, and
      delay in the diagnosis and management can have a detrimental impact on long-term
      development. What is New: * We have demonstrated prior to NICU admission that
      blood glucose concentrations were lower in infants with HH compared to those
      without. * The maximum GIR had a stronger correlation with total length and cost
      of hospital stay compared to insulin levels in HH infants.

PMID- 30232596
TI  - Correction to: A case-control study of the risk of upper gastrointestinal mucosal
      injuries in patients prescribed concurrent NSAIDs and antithrombotic drugs based
      on data from the Japanese national claims database of 13 million accumulated
      patients.
AB  - The authors would like to correct the errors in the publication of the original
      article. The correction details are given below for your reading.

PMID- 30232597
TI  - The role of small intestinal bacterial overgrowth in cystic fibrosis: a
      randomized case-controlled clinical trial with rifaximin.
AB  - BACKGROUND: Scientific literature shows a high prevalence of Small Intestinal
      Bacterial Overgrowth (SIBO) in patients with Cystic Fibrosis (CF). The role of
      SIBO in nutritional status and gastrointestinal symptoms in CF is not known. Our
      aim was to study epidemiology and clinical impact of SIBO while assessing the
      efficacy of rifaximin in eradicating SIBO in CF patients. METHODS: Symptoms
      questionnaire and Glucose Breath Test (GBT) were given to 79 CF patients (median
      age 19.6 years; 9.2-36.9). Subjects with a positive GBT were enrolled in a
      randomized controlled trial and received rifaximin 1200 mg for 14 days or no
      treatment. Questionnaire and GBT were repeated 1 month after the end of treatment
      or 45 days after the first negative GBT. RESULTS: Out of 79 patients, 25 were
      affected by SIBO (31.6%) with a significant correlation with lower BMI, SDS-BMI
      (p < 0.05) and serum albumin levels (p < 0.05), independently from pancreas
      insufficiency. Twenty-three patients took part in the randomized trial, 13
      patients (56.5%) in rifaximin group and 10 patients (43.5%) in control group.
      Eradication rate of SIBO was 9/10 (90%) in rifaximin group and 2/6 (33.3%) in
      control group (p < 0.05). In the rifaximin group, gastrointestinal symptom
      improvement was observed in 4/5 patients aged <= 14 years and in 0/5 patients
      aged > 14 years (p < 0.05); in 2/6 patients in the control group. CONCLUSIONS: CF
      patients show a high prevalence of SIBO, related to a poorer nutritional status.
      Rifaximin therapy is well tolerated and the results are promising in terms of
      efficacy in eradicating small intestinal bacterial overgrowth in CF.

PMID- 30232599
TI  - Transcriptome analysis of root-knot nematode (Meloidogyne incognita)-resistant
      and susceptible sweetpotato cultivars.
AB  - MAIN CONCLUSION: Transcriptome analysis was performed on the roots of susceptible
      and resistant sweetpotato cultivars infected with the major root-knot nematode
      species Meloidogyne incognita. In addition, we identified a transcription factor
      mediated defense signaling pathway that might function in sweetpotato-nematode
      interactions. Root-knot nematodes (RKNs, Meloidogyne spp.) are important
      sedentary endoparasites of many agricultural crop plants that significantly
      reduce production in field-grown sweetpotato. To date, no studies involving gene
      expression profiling in sweetpotato during RKN infection have been reported.
      Therefore, in the present study, transcriptome analysis was performed on the
      roots of susceptible (cv. Yulmi) and resistant (cv. Juhwangmi) sweetpotato
      cultivars infected with the widespread, major RKN species Meloidogyne incognita.
      Using the Illumina HiSeq 2000 platform, we generated 455,295,628 pair-end reads
      from the fibrous roots of both cultivars, which were assembled into 74,733
      transcripts. A number of common and unique genes were differentially expressed in
      susceptible vs. resistant cultivars as a result of RKN infection. We assigned the
      differentially expressed genes into gene ontology categories and used MapMan
      annotation to predict their functional roles and associated biological processes.
      The candidate genes including hormonal signaling-related transcription factors
      and pathogenesis-related genes that could contribute to protection against RKN
      infection in sweetpotato roots were identified and sweetpotato-nematode
      interactions involved in resistance are discussed.

PMID- 30232600
TI  - Human Organotypic Models for Anti-infective Research.
AB  - The use of human organotypic models for biomedical research is experiencing a
      significant increase due to their biological relevance, the possibility to
      perform high-throughput analyses, and their cost efficiency. In the field of anti
      infective research, comprising the search for novel antipathogenic treatments
      including vaccines, efforts have been made to reduce the use of animal models.
      That is due to two main reasons: unreliability of data obtained with animal
      models and the increasing willingness to reduce the use of animals in research
      for ethical reasons. Human three-dimensional (3-D) models may substitute and/or
      complement in vivo studies, to increase the translational value of preclinical
      data. Here, we provide an overview of recent studies utilizing human organotypic
      models, resembling features of the cervix, intestine, lungs, brain, and skin in
      the context of anti-infective research. Furthermore, we focus on the future
      applications of human skin models and present methodological protocols to culture
      human skin equivalents and human skin explants.

PMID- 30232598
TI  - Neglected Mediterranean plant species are valuable resources: the example of
      Cistus ladanifer.
AB  - MAIN CONCLUSION: The combination of genotypic selection, targeted and improved
      cultivation, and processing techniques for specific applications gives C.
      ladanifer the potential to be used as a valuable resource in Mediterranean areas
      with poor agronomic advantages. Cistus ladanifer (rockrose) is a perennial shrub,
      well adapted to the Mediterranean climate and possibly to upcoming environmental
      changes. As a sequence to a thorough review on taxonomic, morphological, chemical
      and competitive aspects of C. ladanifer, the research team focuses here on the
      economic potential of C. ladanifer: from production to applications, highlighting
      also known biological activities of extracts and their compounds. The use of this
      natural resource may be a viable solution for poor and contaminated soils with no
      need for large agricultural techniques, because this species is highly resistant
      to pests, diseases and extreme environmental factors. In addition, this species
      reveals interesting aptitudes that can be applied to food, pharmaceutical,
      phytochemical and biofuel industries. The final synthesis highlights research
      lines toward the exploitation of this neglected resource, such as selection of
      plant lines for specific applications and development of agronomic and processing
      techniques.

PMID- 30232601
TI  - Activity-Based Protein Profiling Methods to Study Bacteria: The Power of Small
      Molecule Electrophiles.
AB  - ABPP methods have been utilized for the last two decades as a means to
      investigate complex proteomes in all three domains of life. Extensive use in
      eukaryotes has provided a more fundamental understanding of the biological
      processes involved in numerous diseases and has driven drug discovery and
      treatment campaigns. However, the use of ABPP in prokaryotes has been less
      common, although it has gained more attention over the last decade. The urgent
      need for understanding bacteriophysiology and bacterial pathogenicity at a
      foundational level has never been more apparent, as the rise in antibiotic
      resistance has resulted in the inadequate and ineffective treatment of
      infections. This is not only a result of resistance to clinically used
      antibiotics, but also a lack of new drugs and equally as important, new drug
      targets. ABPP provides a means for which new, clinically relevant drug targets
      may be identified through gaining insight into biological processes. In this
      chapter, we place particular focus on the discussion of ABPP strategies that have
      been applied to study different classes of bacterial enzymes.

PMID- 30232602
TI  - Enteroaggregative Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAEC, formerly known as "EAggEC") cause acute
      or persistent watery diarrhoea (with or without mucus) in children, predominantly
      in low-income countries, and are associated with travellers' diarrhoea in
      children and adults in middle and high income countries. The diverse nature of
      EAEC is such that not all strains cause disease. Conversely, certain strains of
      EAEC possess additional virulence determinants associated with the ability to
      cause severe diarrhoea and other symptoms, which might be life-threatening in
      vulnerable patients. The EAEC virulence factors described to date are either
      encoded on the large virulence plasmid of EAEC (plasmid of aggregative adherence)
      or on pathogenicity islands on the chromosome. Testing of food and faecal samples
      involves the detection of EAEC-associated traits in the matrix followed by
      isolation of the organism and confirmation of the presence of EAEC-associated
      genes using PCR. The variability of the plasmid structure and virulence gene
      sequences and the possibility that this mobile genetic element may be lost has
      necessitated the inclusion of chromosomal markers in the molecular screening
      assays. There is evidence in the literature of foodborne transmission of EAEC,
      but currently no evidence of a zoonotic reservoir. Fimbriae-mediated adhesion and
      biofilm formation are likely to be involved in both clinical manifestations of
      infection and attachment to foodstuffs. Multidrug resistance appears to be common
      in EAEC and geographically widespread. Whole-genome sequencing has revealed the
      mosaic genomic structure of EAEC and provided evidence that horizontal gene
      transfer and recombination are the driving force for acquisition of novel genome
      features and potentially novel pathogenic mechanisms. This has significant public
      health implications in terms of the diversity and pathogenesis of EAEC and its
      ability to colonise and cause disease in the human host.

PMID- 30232603
TI  - Correction to: Agrobacterium: A Genome-Editing Tool-Delivery System.
AB  - By mistake the chapter was published with incorrect author name. The chapter has
      now been corrected.

PMID- 30232604
TI  - Efficacy of lamivudine prophylaxis in preventing hepatitis B virus reactivation
      in patients with resolved infection undergoing allogeneic SCT and receiving
      rituximab.
AB  - PURPOSE: Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is
      common in patients with hematological malignancies, even in case of resolved
      infection. Prophylaxis of HBV reactivation is universally recommended in stem
      cell transplant (SCT) recipients and patients treated with anti-CD20 agents
      (i.e., rituximab). Despite its well-established favorable safety profile,
      lamivudine (LAM) use in prophylaxis has been debated because of the possible
      emergence of resistant viral strains. The aim of this study was to investigate
      the efficacy of LAM in preventing HBV reactivation in allogeneic SCT recipients
      with a resolved HBV infection. METHODS: Patients who received first allogeneic
      SCT in years 2009-2016 were evaluated. Sixty-three patients with resolved
      infection received LAM prophylaxis and were included in the study. Baseline and
      post-SCT characteristics were recorded, including rituximab exposure, length of
      LAM prophylaxis, and time from transplant to the last clinical and virological
      follow-up. RESULTS: Overall, 39 patients (62%) were male, 39 (62%) had acute
      myeloid leukemia, 38 (60%) received transplant from haploidentical donor, 29
      (53%) received myeloablative conditioning, and 15 (24%) received rituximab post
      transplant. Median clinical follow-up was 24 months after SCT (range 0.3-97);
      median virological follow-up 16 months (range 0.3-78), and median length of LAM
      prophylaxis of 14.5 months (range 0.3-78). No patient experienced HBV
      reactivation while on LAM prophylaxis. One patient experienced reactivation 8
      months after discontinuing prophylaxis. CONCLUSIONS: In this high-risk
      population, LAM prophylaxis was effective in preventing HBV reactivation in
      patients with resolved infection. It should be considered a reasonable first-line
      prophylactic agent to be administered in this setting.

PMID- 30232606
TI  - Host migration strategy and blood parasite infections of three sparrow species
      sympatrically breeding in Southeast Europe.
AB  - Mobile hosts like birds occupy a wide array of habitats in which they encounter
      various vector and parasite faunas. If the infection probability for vector-borne
      parasites varies among seasons and biomes, a migratory life can critically
      influence the infections of a host. The growing body of literature on avian blood
      parasites suggests that host migrations do not only influence prevalence of
      infection but can also evoke higher infection intensities and increased parasite
      diversity in migrant compared to resident host species. We investigated the
      prevalence, intensity and diversity of Plasmodium and Haemoproteus infections in
      three closely-related and sympatrically breeding sparrow species with different
      migration strategies ranging from residential house sparrow and partially
      migratory tree sparrow to the obligate migratory Spanish sparrow. With a
      prevalence of 49%, the migratory Spanish sparrows were significantly less
      frequently infected than the resident house sparrows (82%). The partially
      migratory tree sparrow showed an intermediate prevalence of 60%. The
      parasitaemias were similar in all three host species and indicated mostly chronic
      but also few acute infections. While we found Plasmodium parasites in all three
      sparrow species, only Spanish sparrows were infected with Haemoproteus parasites
      in our study. With nine clearly identified parasite lineages in our study and the
      highest number of lineages per infected individuals (i.e. relative diversity),
      Spanish sparrows harboured the most diverse parasite fauna. Our results suggest
      that migration strategies can affect Plasmodium and Haemoproteus infections of
      sparrows resulting in a lower parasite prevalence and higher parasite diversity
      in migratory hosts-at least during our host's breeding period. A general scope
      for all annual cycle periods and across various bird taxa remains to be
      elucidated.

PMID- 30232605
TI  - Experimental models in Chagas disease: a review of the methodologies applied for
      screening compounds against Trypanosoma cruzi.
AB  - One of the main problems of Chagas disease (CD), the parasitic infection caused
      by Trypanosoma cruzi, is the lack of a completely satisfactory treatment, which
      is currently based on two old nitroheterocyclic drugs (i.e., nifurtimox and
      benznidazole) that show important limitations for treating patients. In this
      context, many laboratories look for alternative therapies potentially applicable
      to the treatment, and therefore, research in CD chemotherapy works in the design
      of experimental protocols for detecting molecules with activity against T. cruzi.
      Phenotypic assays are considered the most valuable strategy for screening these
      antiparasitic compounds. Among them, in vitro experiments are the first step to
      test potential anti-T. cruzi drugs directly on the different parasite forms
      (i.e., epimastigotes, trypomastigotes, and amastigotes) and to detect
      cytotoxicity. Once the putative trypanocidal drug has been identified in vitro,
      it must be moved to in vivo models of T. cruzi infection, to explore (i) acute
      toxicity, (ii) efficacy during the acute infection, and (iii) efficacy in the
      chronic disease. Moreover, in silico approaches for predicting activity have
      emerged as a supporting tool for drug screening procedures. Accordingly, this
      work reviews those in vitro, in vivo, and in silico methods that have been
      routinely applied during the last decades, aiming to discover trypanocidal
      compounds that contribute to developing more effective CD treatments.

PMID- 30232608
TI  - 36-Months follow-up assessment after cessation and resuming of enzyme replacement
      therapy in late onset Pompe disease: data from the Swiss Pompe Registry.
AB  - INTRODUCTION: Although not curative, enzyme replacement therapy (ERT) with
      recombinant human acid alpha-glucosidase enzyme has shown to be effective in the
      treatment of late-onset Pompe disease (LOPD). For this potentially life-long
      treatment, little is known on the clinical effect of cessation and resuming ERT.
      Due to a Swiss supreme court decision on ERT reimbursement, a temporary stop of
      ERT occurred in our study population. The aim of this study was to report the 36
      months follow-up assessments after resuming ERT. METHODS: After resuming ERT,
      seven patients suffering from genetically and enzymatically confirmed LOPD had
      periodic, mandatory, prospective assessments of pulmonary function tests, muscle
      strength summary scores, distances walked in timed walking tests, and patient
      reported questionnaires. Data were statistically analyzed for significant
      differences between time points at ERT cessation, at ERT resuming, and 36 months
      thereafter. RESULTS: After resuming ERT forced vital capacity (p = 0.007) and
      distance walked in the 6 min walk test (6-MWT, p = 0.011) significantly increased
      at 36 months. Compared to before ERT cessation, distance walked in 6-MWT at 36
      months still remained significantly lower (p = 0.005). Self-reported scores in
      the fatigue severity scale significantly declined at 36 months after resuming ERT
      (p = 0.019). No other functional or reported parameter significantly changed at
      36 months after resuming ERT. CONCLUSIONS: Our data suggests that long-term
      interruption of ERT in LOPD may lead to deterioration of clinical meaningful
      parameters and quality of life. In addition, a clinical restoration after ERT
      cessation is possible for most of the LOPD patients within a 36 months follow-up.

PMID- 30232607
TI  - "High-grade oncocytic renal tumor": morphologic, immunohistochemical, and
      molecular genetic study of 14 cases.
AB  - The spectrum of the renal oncocytic tumors has been expanded in recent years to
      include several novel and emerging entities. We describe a cohort of novel,
      hitherto unrecognized and morphologically distinct high-grade oncocytic tumors
      (HOT), currently diagnosed as "unclassified" in the WHO classification. We
      identified 14 HOT by searching multiple institutional archives. Morphologic,
      immunohistochemical (IHC), molecular genetic, and molecular karyotyping studies
      were performed to investigate these tumors. The patients included 3 men and 11
      women, with age range from 25 to 73 years (median 50, mean 49 years). Tumor size
      ranged from 1.5 to 7.0 cm in the greatest dimension (median 3, mean 3.4 cm). The
      tumors were all pT1 stage. Microscopically, they showed nested to solid growth,
      and focal tubulocystic architecture. The neoplastic cells were uniform with
      voluminous oncocytic cytoplasm. Prominent intracytoplasmic vacuoles were
      frequently seen, but no irregular (raisinoid) nuclei or perinuclear halos were
      present. All tumors demonstrated prominent nucleoli (WHO/ISUP grade 3
      equivalent). Nine of 14 cases were positive for CD117 and cytokeratin (CK) 7 was
      either negative or only focally positive in of 6/14 cases. All tumors were
      positive for AE1-AE3, CK18, PAX 8, antimitochondrial antigen, and SDHB. Cathepsin
      K was positive in 13/14 cases and CD10 was positive in 12/13 cases. All cases
      were negative for TFE3, HMB45, Melan-A. No TFEB and TFE3 genes rearrangement was
      found in analyzable cases. By array CGH, complete chromosomal losses or gains
      were not found in any of the cases, and 3/9 cases showed absence of any
      abnormalities. Chromosomal losses were detected on chromosome 19 (4/9), 3 with
      losses of the short arm (p) and 1 with losses of both arms (p and q). Loss of
      chromosome 1 was found in 3/9 cases; gain of 5q was found in 1/9 cases. On
      molecular karyotyping, 3/3 evaluated cases showed loss of heterozygosity (LOH) on
      16p11.2-11.1 and 2/3 cases showed LOH at 7q31.31. Copy number (CN) losses were
      found at 7q11.21 (3/3), Xp11.21 (3/3), Xp11.22-11.21 (3/3), and Xq24-25 (2/3). CN
      gains were found at 13q34 (2/3). Ten patients with available follow up
      information were alive and without disease progression, after a mean follow-up of
      28 months (1 to 112 months). HOT is a tumor with unique morphology and its IHC
      profile appears mostly consistent. HOT should be considered as an emerging renal
      entity because it does not meet the diagnostic criteria for other recognized
      eosinophilic renal tumors, such as oncocytoma, chromophobe renal cell carcinoma
      (RCC), TFE3 and TFEB RCC, SDH-deficient RCC, and eosinophilic solid and cystic
      RCC.

PMID- 30232609
TI  - Identifying barriers to help-seeking for sexual dysfunction in multiple
      sclerosis.
AB  - BACKGROUND: Sexual dysfunction (SD) is common in multiple sclerosis (MS),
      however, under-reported. OBJECTIVE: The aim of this study was to identify
      barriers faced by patients with MS and healthcare professionals (HCPs) in
      discussing SD. METHODS: This was a two-part prospective study carried out at a
      tertiary care centre. Patients with MS were surveyed using a 29-item
      questionnaire and SD was assessed using the MSISQ and ASEX questionnaires;
      depression screened with PHQ-2. HCPs were surveyed using a 23-item questionnaire.
      RESULTS: Seventy four patients (mean age 42.4 +/- 10.7, 54 females) and 98 HCPs
      (mean age 45.8 +/- 8.9, 90 females) participated. SD was significant, with
      primary (36.4%), secondary (27%) and tertiary (29.8%) contributory factors.
      Commonest barriers reported by patients were dominance of neurological symptoms
      (N = 30, 40.5%), presence of family or friends (N = 28, 37.8%), and not being
      asked (N = 25, 33.8%), while HCPs reported presence of family or friends (N = 34,
      34.7%), lack of knowledge about SD (N = 30, 30.6%), and inadequate time during
      the consultation (N = 27, 27.6%). CONCLUSIONS: Barriers to discussing SD are
      similar between patients and HCPs. The most common barriers are addressable
      through modifications in the clinic environment, raising awareness and providing
      training opportunities.

PMID- 30232610
TI  - Migraine prophylactic management in neurology and primary care (2006-2015).

PMID- 30232611
TI  - Cucurbit aphid-borne yellows virus from melon plants in Brazil is an
      interspecific recombinant.
AB  - Melon plants with severe yellowing symptoms from in Brazil were analyzed by high
      throughput sequencing. Sequences homologous to the genome of the polerovirus
      cucurbit aphid-borne yellows virus (CABYV) were frequently retrieved. Two draft
      CABYV genomes were assembled from two pooled melon samples that contained an
      identical putative recombinant fragment in the 3' region with an unknown
      polerovirus. The complete genomes of these isolates revealed by Sanger sequencing
      share 96.8% nucleotide identity, while both sequences share 73.7% nucleotide
      identity with a CABYV-N isolate from France. A molecular-clock analysis suggested
      that CABYV was introduced into Brazil ~ 68 years ago.

PMID- 30232612
TI  - Recombination of host cell mRNA with the Asia 1 foot-and-mouth disease virus
      genome in cell suspension culture.
AB  - Foot-and-mouth disease virus (FMDV) exhibits high mutation rates during
      replication. In this study, an isolate of FMDV serotype Asia-1 was serially
      passaged in a BHK-21 cell monolayer and then adapted to serum-free BHK-21 cell
      suspension culture to produce a seed virus for production of an inactivated
      vaccine. Analysis of the sequence encoding the structural proteins of the virus
      at various passages showed the presence of overlapping peaks in sequencing
      electropherograms after nucleotide 619 of VP1 in viruses recovered from the
      fourth passage in suspension culture, suggesting the possible introduction of an
      insertion or deletion into this portion of the viral genome of our seed virus
      stock. To evaluate this phenomenon, a virus designated "Vac-Asia1-VDLV", was
      isolated by plaque purification from the tenth passage in suspension culture.
      Sequencing results showed that a 12-nt-long exogenous sequence was inserted into
      the 3' end of the VP1 coding region at the position where the original
      overlapping peaks were identified. Analysis of the host cell transcriptome showed
      that the 12-nt sequence was identical to a highly expressed sequence in BHK-21
      cells, strongly suggesting that recombination between the FMDV genome and host
      cell mRNA produced the recombinant virus. A growth curve showed that the virus
      with the 12-nt insertion reached a peak earlier than the parental strain and that
      this virus had acquired the ability to bind to the cell surface by a mechanism
      that was not dependent on integrin or the heparan sulfate receptor. This novel
      pathogen-host cell recombination event is discussed in terms of the mechanism of
      viral RNA replication and the phenotypic constraints of FMDV biology and
      evolution.

PMID- 30232613
TI  - A Victorivirus from Fusarium asiaticum, the pathogen of Fusarium head blight in
      China.
AB  - A Victorivirus was detected in isolate F16176 of the fungus Fusarium asiaticum,
      the causal agent of Fusarium head blight in China. The full genome sequence of
      the virus was sequenced and characterized. The complete cDNA sequence is 5,281
      nucleotides long with 64.2% G + C content and contains two open reading frames
      (ORFs) that overlap at the pentanucleotide UAAUG. The two ORFs are predicted to
      encode coat protein (CP) and RNA-dependent RNA polymerase (RdRp), which are
      conserved among the dsRNA mycoviruses of the genus Victorivirus. Pairwise
      comparisons and phylogenetic analysis of the deduced amino acid sequences of RdRp
      indicated that this dsRNA mycovirus is a new virus belonging to the species
      Rosellinia necatrix victorivirus 1 in the family Totiviridae. This study is the
      first to report a full-length genomic sequence of a putative member of the genus
      Victorivirus in F. asiaticum.

PMID- 30232614
TI  - The complete genomic sequence of Rhinolophus gammaherpesvirus 1 isolated from a
      greater horseshoe bat.
AB  - In a comprehensive research project on bat viruses, we successfully isolated a
      novel herpesvirus from the spleen of a greater horseshoe bat (Rhinolophus
      ferrumequinum) in Japan using a cell line established from the kidney of the same
      bat. This herpesvirus was a novel gammaherpesvirus (Rhinolophus gammaherpesvirus
      1; RGHV-1), which belonged to the genus Percavirus. The whole RGHV-1 genome
      (147,790 bp) showed that 12 of the 84 genes predicted to contain open reading
      frames did not show any homology to those of other herpesviruses.

PMID- 30232617
TI  - Postoperative bleeding after laparoscopic Roux en Y gastric bypass: predictors
      and consequences.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a common, safe and
      effective bariatric procedure. Bleeding is a significant source of postoperative
      morbidity. We aimed to determine the incidence, outcomes, and predictors of
      postoperative bleeding after LRYGB. METHODS: LRYGB patients included in the
      Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program
      (MBSAQIP) 2015 dataset were identified. Preoperative and intraoperative factors
      were tested for associations with bleeding using univariable and multivariable
      logistic regression analysis. Outcomes of length of stay, in-hospital mortality,
      30-day mortality, discharge disposition, and 30-day complications among patients
      with and without clinically significant postoperative bleeding were compared
      using multivariable regression. RESULTS: In the 43,280 LRYGB patients included in
      this analysis, postoperative bleeding occurred in 652 (1.51%) patients. Of these,
      165 (25.3%) underwent a re-operation and 97 (14.9%) underwent an unplanned
      endoscopy for 'bleeding'. Postoperative bleeding was associated with a longer
      median postoperative length of stay (4 vs. 2 days), higher in-hospital mortality
      (1.23 vs. 0.04%), higher 30-day mortality (1.38 vs. 0.15%), discharge to an
      extended-care facility (3.88 vs. 0.6%), and higher rates of major complications
      (all P < 0.05). Independent predictors of postoperative bleeding included; a
      history of renal insufficiency (OR 2.55, 95% CI 1.43-4.52), preoperative
      therapeutic anticoagulation (OR 2.44, 95% CI 1.69-3.53), and revisional surgery
      (OR 1.45, 95% CI 1.06-1.97). Intraoperative associated factors included
      conversions (OR 3.37, 95% CI 1.42-7.97), and drain placement (OR 1.40, 95% CI
      1.18-1.67). Robotic approaches resulted in independently lower postoperative
      bleeding rates (OR 0.50, 95% CI 0.32-0.77). CONCLUSIONS: Postoperative bleeding
      occurs in 1.5% of patients undergoing a LRYGB and is associated with
      significantly increased morbidity and mortality. We have identified patient and
      operative factors that are independently associated with postoperative bleeding.

PMID- 30232616
TI  - Intraoperative confocal laser endomicroscopy for real-time in vivo tissue
      characterization during surgical procedures.
AB  - INTRODUCTION: Probe-based confocal laser endomicroscopy (pCLE) is an innovative
      technique providing real-time, in vivo optical biopsies. A previous ex vivo phase
      of the study (PERSEE) allowed identifying accurate pCLE criteria for the
      diagnosis of hepatic and peritoneal surgical specimens. This study aimed at
      evaluating the pCLE role for in vivo intra-abdominal tissue characterization
      during digestive cancer surgical procedures. METHODS: Between October 2014 and
      July 2015, consecutive patients diagnosed with digestive cancers and scheduled
      for a surgical resection or an exploratory laparoscopy were prospectively
      enrolled. Endomicroscopic images were acquired using a motorized Confocal
      MiniprobeTM with a bending distal tip providing easy access to abdominal organs.
      It was connected to an endomicroscopy system that allowed near-infrared
      illumination (at a wavelength of 785 nm) in conjunction with indocyanine green
      for contrast agent. A live audiovisual transmission was established between the
      surgeon and the pathologist for real-time interpretation of optical biopsies.
      Intraoperative pCLE performance for the diagnosis of suspicious nodules was
      assessed using corresponding surgical histopathology as reference standard.
      RESULTS: 21 consecutive patients were successfully enrolled. Live audiovisual
      transmission between the surgeon and the pathologist was successfully established
      in all cases. 62 pCLE sequences were acquired from different tissues [peritoneum
      (n = 27), liver (n = 21), lymph node (n = 4), diaphragm (n = 3), colon (n = 3),
      stomach (n = 2), and adrenal gland (n = 2)]. Malignant tissues were identified by
      fluorescently enhanced irregular cancerous tubes contrasting with dark glandular
      lumen and extracellular matrix. pCLE sensitivities and specificities were 67% and
      100%, and 38% and 100% for peritoneal and hepatic carcinogenesis, respectively.
      One benign incident was reported during the trial with no patient consequence.
      CONCLUSIONS: Real-time intraoperative pCLE with near-infrared illumination is
      feasible and safe, provides additional information in terms of tissue
      characterization, and, in combination with telepathology, allows interactive
      collaboration between the surgeon and the pathologist during surgical procedures.
      Trial registration clinicaltrials.gov Identifier: NCT02312167.

PMID- 30232618
TI  - Long-term outcomes following POEM for non-achalasia motility disorders of the
      esophagus.
AB  - BACKGROUND: Optimal treatment for symptomatic patients with non-achalasia
      motility disorders (NAD) such as diffuse esophageal spasm, esophagogastric
      junction outlet obstruction, and hypercontractile disorder is not well
      established. POEM has been offered to these patients since it is a less invasive
      and less morbid procedure but long-term outcomes remain undetermined. The aim of
      this study was to assess long-term outcomes of POEM for patients with NAD.
      METHODS: Records of 40 consecutive patients undergoing POEM for NAD from May 2011
      to January 2016 at a single center were retrospectively reviewed. Preoperative
      and 6-month postoperative symptom scores, high-resolution manometry, pH testing,
      and timed barium swallow (TBS) data were collected. Patients were contacted by
      phone to obtain long-term symptom assessment. Symptoms were assessed using a
      standardized symptom questionnaire with scores for symptoms graded according to
      frequency and the Eckardt score. RESULTS: Ten percent had minor complications
      with no postoperative sequelae. 90% of patients had significant improvement in
      their mean Eckardt scores (5.02 vs. 1.12, p < 0.001) at early follow-up.
      Improvements in chest pain (1.02-0.36, p = 0.001) and dysphagia (2.20 vs. 0.40, p
      = 0.001) were seen. Significant improvements in manometric pressures and
      esophageal emptying on TBS were observed across groups. 38% (10/26) of patients
      had a postoperative pH score > 14.72. Long-term (median 48 months) symptom scores
      were obtained from 29 (72.5%) patients. 82% of patients (24/29) had sustained
      symptom improvement. A small increase in the dysphagia scores was reported in the
      long-term follow-up compared to the immediate postoperative period (0.36-0.89, p
      = 0.046). CONCLUSIONS: Chest pain and dysphagia are effectively palliated with
      POEM in patients with non-achalasia disorders of the esophagus. Significant
      improvements are durable in long-term follow-up. Despite earlier reports by our
      group suggesting possible inferior outcomes from POEM for this difficult group of
      patients, this study is far more encouraging. POEM should be considered in the
      treatment of patients with non-achalasia disorders of the esophagus.

PMID- 30232615
TI  - Carabidae Semiochemistry: Current and Future Directions.
AB  - Ground beetles (Carabidae) are recognized for their diverse, chemically-mediated
      defensive behaviors. Produced using a pair of pygidial glands, over 250 chemical
      constituents have been characterized across the family thus far, many of which
      are considered allomones. Over the past century, our knowledge of Carabidae
      exocrine chemistry has increased substantially, yet the role of these defensive
      compounds in mediating behavior other than repelling predators is largely
      unknown. It is also unclear whether non-defensive compounds produced by ground
      beetles mediate conspecific and heterospecific interactions, such as sex
      aggregation pheromones or kairomones, respectively. Here we review the current
      state of non-exocrine Carabidae semiochemistry and behavioral research, discuss
      the importance of semiochemical research including but not limited to allomones,
      and describe next-generation methods for elucidating the underlying genetics and
      evolution of chemically-mediated behavior.

PMID- 30232620
TI  - Evaluation of soil hydraulic properties under different non-agricultural land use
      patterns in a basement complex area using multivariate statistical analysis.
AB  - The knowledge about effects of different land use patterns on soil hydraulic
      properties is essential for best land management practices. This study examined
      hydraulic properties under different non-agricultural land uses in parts of
      Abeokuta, Southwest Nigeria. Fifteen clusters surface soil samples at a depth of
      0-20 cm were collected from five sites on the same geological setting under the
      following land uses: grassland (control), dumpsite (DS), animal waste site (AWS),
      quarry site (QS), and block making site (BMS). The calculated values of
      associated hydraulic properties and Ksat were used to develop three model
      equations. Pearson's correlation, coefficient of variation (CV), analysis of
      variance (ANOVA), cluster analysis (CA), and principal component analysis (PCA)
      were used to study the variations and correlation of analyzed soil properties
      under different land uses. Porosity and water holding capacity (WHC) of all the
      other land uses were increased relative to the control site (CS) while soil bulk
      density (BD) in control was reduced when compared to soils under other different
      land use patterns. However, BMS and QS increased Ksat relative to the CS. Soils
      in all land use patterns belong to sandy loam except CS. Correlation coefficient
      revealed a strong negative correlation between BD and porosity and strong
      positive correlation between % clay and WHC. Comparison among the regression
      models showed that Ksat predicted from semi-log model with R2 = 0.645 estimated
      better than both linear and double-long models. The use of PCA resulted in four
      principal factors accounting for 97.24% of the total variance. The result of CA
      shows groups based on similar soil hydraulic property, distinct soil property
      value, and erosional indicator. ANOVA showed that there was significant
      difference at 5% level (P < 0.05) among all selected land use patterns with
      respect to BD and porosity. This indicates that BD and porosity can be considered
      as dynamic soil hydraulic indicators that are strongly affected by land use
      systems.

PMID- 30232621
TI  - Knowledge, Awareness, and Eye Care-Seeking Behavior in Diabetic Retinopathy: A
      Cross-Sectional Study in Jeddah, Kingdom of Saudi Arabia.
AB  - INTRODUCTION: Diabetes mellitus (DM) is common metabolic disorder that is
      characterized by increased circulating blood glucose levels. Long-term,
      continuous hyperglycemia leads to vasculature-related disorders, including those
      affecting the eyes, such as retinopathy. The objective of this study was to
      assess the awareness of diabetic complications, specifically diabetic
      retinopathy, among diabetic patients attending the Jeddah Eye Hospital. METHODS:
      This was a cross-sectional study targeting the outpatient clinics of Jeddah Eye
      Hospital for a period of 2 months. A total of 380 participants were randomly
      selected based on sample size calculations. A closed-ended questionnaire,
      generated after an extensive literature review, was distributed among the
      selected individuals. The questions focused on the participants' clinical status
      of DM, socio-demographic characteristics, awareness of eye complications
      secondary to DM, eye screening, and eye care-seeking behavior. RESULTS: The mean
      age of the patients was 58.3 (standard deviation 10.9) years, and 52.4% of
      patients were female. The majority (89.7%) of participants had type II DM (T2DM).
      The level of awareness was satisfactory (92.4%); however, only 10.5% of
      participants knew the recommended frequency for eye check-ups. The level of
      awareness of related complications was directly influenced by education level,
      source of patient information, place of residence, and frequency of follow-up
      visits. CONCLUSION: The results of this study indicate that although the
      awareness of diabetes-related eye complications was satisfactory in the patient
      population, eye care-seeking behavior and frequency of eye check-ups were not
      optimal. Efforts are needed to promote eye care-seeking behavior in this patient
      group.

PMID- 30232619
TI  - Reference gene validation for normalization of RT-qPCR assay associated with
      germination and survival of rice under hypoxic condition.
AB  - Study on expression of genes for the traits associated with hypoxia tolerance
      during the germination demands robust choice of reference genes for transcript
      data normalization and gene validation through real-time quantitative polymerase
      chain reaction (RT-qPCR). However, reliability and stability of reference genes
      across different rice germplasms under hypoxic condition have not been accessed
      yet. Stability performance of reference genes such as eukaryotic elongation
      factor 1 alpha (eEF1alpha), ubiquitin 10 (UBQ10), glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH), 18S ribosomal RNA (18SrRNA), 25S ribosomal RNA (25SrRNA),
      beta-tublin (beta-TUB), actin11 (ACT11), ubiquitin C (UBC), eukaryotic elongation
      factor 4 alpha (eIF4alpha), and ubiquitin5 (UBQ5) was accessed through
      statistical algorithms like geNorm, NormFinder, Comparative DeltaCt method,
      BestKeeper, and RefFinder in three rice germplasms (KHO, RKB, and IR-64) with
      varied level of tolerance to hypoxic condition during germination. Among all
      genes used, OsGAPDH was found to be the most suitable reference gene under
      hypoxic condition. The performance of the highest-ranking reference gene
      (OsGAPDH) in terms of stability based on statistical algorithms was further
      validated for its reliability and stability through RT-qPCR with hypoxia-induced
      target gene OsTTP7. The identified stable housekeeping gene could be used as
      internal control for gene expression analysis in rice under hypoxia.

PMID- 30232623
TI  - Influence of the amplitude of different side-to-side toothbrushes on noncontact
      biofilm removal.
AB  - OBJECTIVES: To investigate the impact of the lateral deflection of toothbrush
      bristles (amplitude) of three side-to-side toothbrushes for noncontact biofilm
      removal in an artificial interdental space model. MATERIALS AND METHODS: A three
      species biofilm (Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus
      sanguinis) was formed in vitro on protein-coated titanium disks. A flow chamber
      system was combined with a static biofilm growth model. The amplitudes of three
      commercial side-to-side toothbrushes were evaluated by means of a dose response
      analysis. The amplitudes were decreased in steps (100%, 85%, 70%, 55%, and 40%).
      Subsequently, the biofilm-coated substrates were exposed to the toothbrushes. The
      biofilms were analyzed with confocal laser scanning microscope images and
      measured using volumetric analyses. RESULTS: The predictability of interdental
      biofilm reduction differed among the toothbrushes. A lower variety in the results
      of repeated experiments occurred in toothbrush C compared to toothbrushes A and
      B. Toothbrush C obtained highest percentage of biofilm reduction by 85% of
      amplitude power setting (median biofilm reduction 76%). Decreasing the amplitude
      from 85 to 40% resulted in reduced biofilm reduction (p = 0.029). In contrast, no
      significance could be observed for the differences of the tested amplitudes
      within toothbrushes A and B (p > 0.05). Between the toothbrushes, a significant
      difference in interdental biofilm reduction was found between C-A (p = 0.029) and
      C-B (p = 0.029) with amplitude of 85%. CONCLUSIONS: The amplitude of one of the
      investigated side-to-side toothbrushes affected the biofilm reduction predictably
      in an interdental space model. CLINICAL RELEVANCE: Within certain toothbrushes, a
      specific amplitude power setting may demonstrate beneficial effects on noncontact
      biofilm removal.

PMID- 30232625
TI  - Evaluation of the efficacy of calcium silicate vs. glass ionomer cement indirect
      pulp capping and restoration assessment criteria: a randomised controlled
      clinical trial-2-year results.
AB  - OBJECTIVES: Assess calcium silicate cement (BiodentineTM) vs. glass ionomer
      cement (Fuji IXTM, control) as indirect pulp capping (IPC) materials in patients
      with reversible pulpitis after a 2-year follow-up. Evaluate the integrity of the
      overlying resin composite restorations using modified USPHS criteria and FDI
      criteria. Investigate the sensitivity of the modified USPHS criteria compared to
      the FDI criteria in the assessment of the restorations. MATERIALS AND METHODS:
      Seventy-two restorations (36 BiodentineTM, 36 Fuji IXTM) were placed randomly in
      53 patients. Periapical radiographs were taken at pre-treatment (T0), 12-month
      (T12), and 24-month (T24) review. Restorations were assessed using the modified
      USPHS and FDI criteria at T12 and T24. RESULTS: At 24 months, 15 teeth had failed
      to maintain vitality (6 BiodentineTM, 9 Fuji IXTM). Clinical success rate of IPC
      for both materials was 72% and is related to the intensity of reversible pulpitis
      symptoms. No difference was found between T12 and T24 in the periapical (PA)
      radiographs and in the integrity of the resin composite restorations overlying
      BiodentineTM compared to Fuji IXTM. There was no difference in the efficacy of
      the USPHS criteria compared to the FDI criteria in the assessment of the resin
      composite restorations. CONCLUSIONS: BiodentineTM and Fuji IXTM were clinically
      effective when used as IPC materials in teeth with reversible pulpitis at T24.
      Resin composite restorations overlying both materials performed well at T24.
      Using the USPHS or FDI criteria is equally efficient at T24; however, longer term
      follow-up is needed to establish whether there are sensitivity differences
      between these assessment criteria. CLINICAL SIGNIFICANCE: Teeth with deep carious
      lesions approaching the pulp and with signs of reversible pulpitis can be treated
      successfully by indirect pulp capping using either BiodentineTM or Fuji IXTM.
      Using the USPHS or FDI criteria to assess restorations is equally effective at 2
      years. TRIAL REGISTRATION: NCT02201641.

PMID- 30232624
TI  - Metallic crown-induced occlusal trauma as a protocol to evaluate inflammatory
      response in temporomandibular joint and periodontal tissues of rats.
AB  - OBJECTIVES: The goal of this study is to propose a standard protocol of
      experimental occlusal trauma to evaluate the inflammatory hyperalgesia induced by
      metallic crowns on orofacial tissues of rats. MATERIALS AND METHODS: Thirty
      animals were randomly divided into six groups (n = 5 per group). Detailed
      methodology on the manufacturing of metallic crowns is described. The
      inflammatory hyperalgesia induced by occlusal interference was evaluated by intra
      articular injection of a low dose of 0.5% formalin (30 MUl) or vehicle (saline)
      into temporomandibular joint, 21 or 28 days after metallic crown cementation.
      Posteriorly, pro-inflammatory cytokines were evaluated by enzyme-linked
      immunosorbent assay to assess the effect of occlusal interference on
      periodontium. RESULTS: The cementation of metallic crowns with dental anatomy on
      the lower molar of rats does not show signs of stress and lack of feeding.
      Metallic crown-induced occlusal trauma results in a temporomandibular joint
      inflammatory hyperalgesia (P < 0.05: ANOVA, Tukey's test). Otherwise, it was
      observed that occlusal trauma results in the increase of protein level of pro
      inflammatory cytokines TNF-alpha and IL-1beta in the gingival tissues (P < 0.05).
      CONCLUSION: This study demonstrates in detail a methodology of occlusal trauma
      resulting from the cementation of metallic crowns in the lower molars of rats,
      mimicking occlusal interferences commonly evaluated in the dental clinic. This
      methodology makes new studies to better understand the mechanisms involved in the
      occlusal trauma of orofacial tissues possible. CLINICAL RELEVANCE: The
      standardization of an experimental occlusal interference model will allow us to
      understand the deleterious effect and mechanisms that affect the orofacial
      tissues.

PMID- 30232626
TI  - Effect of cold plasma on periodontal wound healing-an in vitro study.
AB  - OBJECTIVES: Cold atmospheric plasma (CAP), a room temperate ionized gas, seems to
      be a possible way to enhance tissue recovery. An in vitro study was conducted to
      investigate the influence of medical CAP on the regenerative capacity of human
      periodontal ligament (PDL) cells. MATERIAL AND METHODS: Human PDL cells were
      subjected to CAP at various intensities, distances, and durations. The effects of
      CAP on a number of specific markers were studied at transcriptional level using
      real-time PCR. Additionally, an in vitro wound healing assay was applied to PDL
      cell monolayers either in the presence or absence of CAP by using JuLITM Br Live
      Cell Analyzer and software. Finally, cell viability of CAP-treated cells was
      analyzed by an XTT assay. RESULTS: CAP treatment enhanced significantly the
      expression of the cytokines tumor necrosis factor (TNF)alpha, cyclooxygenase
      (COX)2, interleukin (IL)-1beta, IL-6, IL-8, collagen (COL)1alpha, and matrix
      metalloproteinase (MMP)1, as well as the proliferation markers Ki67 and
      proliferating cell nuclear antigen (PCNA), but downregulated apoptotic markers
      Apaf1 and p53. Additionally, the in vitro wound healing rate was significantly
      enhanced after CAP application. Moreover, CAP treatment resulted in a
      significantly increased cell viability in the XTT assay. CONCLUSION: This in
      vitro study shows that CAP has regulatable effects on markers of periodontal
      wound healing thereby underlining the potential use of CAP as a benefit treatment
      strategy. CLINICAL RELEVANCE: Our study demonstrates the application of CAP in
      the treatment of oral pathologies suggesting a promising future treatment
      approach.

PMID- 30232627
TI  - Clinical evaluation of non-surgical cleaning modalities on titanium dental
      implants during maintenance care: a 1-year follow-up on prosthodontic
      superstructures.
AB  - OBJECTIVES: To investigate tissue health around implants with newly attached
      superstructures over 12 months of preventive maintenance appointments and
      instrumentation when necessary. MATERIAL AND METHODS: In a randomized, split
      mouth study 32 implants (8 participants with 4 implants each) received followed
      up care every 3 months after superstructure attachment. Implants and
      superstructures were randomly assigned to four treatment groups and treated if
      necessary: (1) titanium curettes (TC), (2) stainless steel ultrasonic tip (PS),
      (3) erythritol air-polishing powder (EP), or (4) rubber cup polishing (CON).
      Probing depths (PDs), bleeding on probing (BOP), modified gingival (mucosal)
      bleeding index (GBI) around implants, and full-mouth Plaque Control Record (PCR)
      were measured every 3 months. Clinical attachment levels (CALs) and height of
      keratinized mucosa (KM)/gingival margins (GMs) for implants/teeth and PD, BOP,
      and GBI for teeth were documented at baseline, 6 months, and 12 months. Matrix
      metalloproteinase 8 (MMP-8) and periopathogens were measured at baseline and 12
      months. RESULTS: Participants exhibited minimal signs of periodontal inflammation
      with statistically significant PD improvement (3.0 +/- 0.2 to 2.8 +/- 0.3 mm; p =
      0.022) and overall CAL (4.3 +/- 0.8 to 4.0 +/- 0.7 mm; p = 0.048) after 1 year.
      Implants showed no statistically significant differences (p > 0.05) between or
      within groups at baseline or 12 months for any parameter, except MMP-8 decreased
      significantly for PS (14.50 +/- 17.58 to 4.63 +/- 7.56 ng; p = 0.044), and after
      12 months, PCR showed a significant difference between TC and PS (p = 0.018).
      CONCLUSIONS: Treatment was necessary as inflammation was observed around newly
      placed superstructures within the first year of maintenance care. All tested
      treatment modalities yielded comparable clinical improvements. CLINICAL
      RELEVANCE: Early assessment and diagnosis of mucositis and regular maintenance
      can promote long-lasting implant health.

PMID- 30232622
TI  - Survival percentages of atraumatic restorative treatment (ART) restorations and
      sealants in posterior teeth: an updated systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of the present study is to update the results of two previous
      meta-analyses, published in 2006 and 2012, on the survival percentages of
      atraumatic restorative treatment (ART) restorations and ART sealants. The current
      meta-analysis includes Chinese publications not investigated before. MATERIALS
      AND METHODS: Until February 2017, six databases were interrogated (two English,
      one Portuguese, one Spanish and two Chinese). Using six exclusion criteria, a
      group of six independent reviewers selected 43 publications from a total of 1958
      potentially relevant studies retrieved. Confidence intervals and/or standard
      errors were calculated and the heterogeneity variance of the survival rates was
      estimated. RESULTS: The survival percentages and standard errors of single
      surface and multiple-surface ART restorations in primary posterior teeth over the
      first 2 years were 94.3% (+/- 1.5) and 65.4% (+/- 3.9), respectively; for single
      surface ART restorations in permanent posterior teeth over the first 3 years,
      they were 87.1% (+/- 3.2); and for multiple-surface ART restorations in permanent
      posterior teeth over the first 5 years, they were 77% (+/- 9.0). The mean annual
      dentine-carious-lesion-failure percentages in previously sealed pits and fissures
      using ART sealants in permanent posterior teeth over the first 3 and 5 years were
      0.9 and 1.9%, respectively. CONCLUSIONS: ART single-surface restorations
      presented high survival percentages in both primary and permanent posterior
      teeth, whilst ART multiple-surface restorations presented lower survival
      percentages. ART sealants presented a high-caries-preventive effect. CLINICAL
      RELEVANCE: ART is an effective evidence-based option for treating and preventing
      carious lesions in primary and permanent posterior teeth.

PMID- 30232628
TI  - An Overview of the Ultrawide Bandgap Ga2O3 Semiconductor-Based Schottky Barrier
      Diode for Power Electronics Application.
AB  - Gallium oxide (Ga2O3) is a new semiconductor material which has the advantage of
      ultrawide bandgap, high breakdown electric field, and large Baliga's figure of
      merit (BFOM), so it is a promising candidate for the next-generation high-power
      devices including Schottky barrier diode (SBD). In this paper, the basic physical
      properties of Ga2O3 semiconductor have been analyzed. And the recent
      investigations on the Ga2O3-based SBD have been reviewed. Meanwhile, various
      methods for improving the performances including breakdown voltage and on
      resistance have been summarized and compared. Finally, the prospect of Ga2O3
      based SBD for power electronics application has been analyzed.

PMID- 30232629
TI  - Trend estimation for complex survey designs of water chemistry indicators from
      Sierra Nevada Lakes.
AB  - Surveys for long-term monitoring programs managing natural resources often
      incorporate sampling design complexity. However, design weights are often ignored
      in trend models of data from complex sampling designs. Generalized random
      tessellation stratified samples of a simulated population of lakes are selected
      with various levels of survey design complexity, and three trend approaches are
      compared. We compare an unweighted trend model, linear regression models of the
      trend in design-based estimates of annual status, and a probability-weighted
      iterative generalized least squares (PWIGLS) approach with a linearization
      variance. The bias and confidence interval coverage of the trend estimate and the
      size and power of the trend test are used to evaluate weighted and unweighted
      approaches. We find that the unweighted approach often outperforms the other
      trend approaches by providing high power for trend detection and nominal
      confidence interval coverage of the true trend regression parameter. We also find
      that variance composition and revisit design structure affect the performance of
      the PWIGLS estimator. When a subpopulation exhibiting an extreme trend is sampled
      disproportionately to its occurrence in the population, the unweighted approach
      may produce biased estimates of trend with poor confidence interval coverage. We
      recommend considering variance composition and potential subpopulation trends
      when selecting sampling designs and trend analysis approaches.

PMID- 30232630
TI  - Advancing Measurement of Diabetes at the Population Level.
AB  - PURPOSE: The measurement and estimation of diabetes in populations guides
      resource allocation, health priorities, and can influence practice and future
      research. To provide a critical reflection on current diabetes surveillance, we
      provide in-depth discussion about how upstream determinants, prevalence,
      incidence, and downstream impacts of diabetes are measured in the USA, and the
      challenges in obtaining valid, accurate, and precise estimates. FINDINGS: Current
      estimates of the burden of diabetes risk are obtained through national surveys,
      health systems data, registries, and administrative data. Several methodological
      nuances influence accurate estimates of the population-level burden of diabetes,
      including biases in selection and response rates, representation of population
      subgroups, accuracy of reporting of diabetes status, variation in biochemical
      testing, and definitions of diabetes used by investigators. Technological
      innovations and analytical approaches (e.g., data linkage to outcomes data like
      the National Death Index) may help address some, but not all, of these concerns,
      and additional methodological advances and validation are still needed. Current
      surveillance efforts are imperfect, but measures consistently collected and
      analyzed over several decades enable useful comparisons over time. In addition,
      we proposed that focused subsampling, use of technology, data linkages, and
      innovative sensitivity analyses can substantially advance population-level
      estimation.

PMID- 30232633
TI  - Design, synthesis and biological potential of heterocyclic benzoxazole scaffolds
      as promising antimicrobial and anticancer agents.
AB  - BACKGROUND: Benzoxazole is the most important class of heterocyclic compound in
      medicinal chemistry. It has been incorporated in many medicinal compounds making
      it a versatile heterocyclic compound that possess a wide spectrum of biological
      activities. RESULTS: The molecular structures of synthesized benzoxazole
      derivatives were confirmed by physicochemical and spectral means. The synthesized
      compounds were further evaluated for their in vitro biological potentials i.e.
      antimicrobial activity against selected microbial species using tube dilution
      method and antiproliferative activity against human colorectal carcinoma (HCT
      116) cancer cell line by Sulforhodamine B assay. CONCLUSION: In vitro
      antimicrobial results demonstrated that compounds 4, 5, 7 and 16 showed promising
      antimicrobial potential. The in vitro anticancer activity indicated that
      compounds 4 and 16 showed promising anticancer activity against human colorectal
      cancer cell line (HCT 116) when compared to standard drug and these compounds may
      serve as lead compound for further development of novel antimicrobial and
      anticancer agents.

PMID- 30232632
TI  - Systematic Review of an Automated Multiclass Detection and Classification System
      for Acute Leukaemia in Terms of Evaluation and Benchmarking, Open Challenges,
      Issues and Methodological Aspects.
AB  - This study aims to systematically review prior research on the evaluation and
      benchmarking of automated acute leukaemia classification tasks. The review
      depends on three reliable search engines: ScienceDirect, Web of Science and IEEE
      Xplore. A research taxonomy developed for the review considers a wide perspective
      for automated detection and classification of acute leukaemia research and
      reflects the usage trends in the evaluation criteria in this field. The developed
      taxonomy consists of three main research directions in this domain. The taxonomy
      involves two phases. The first phase includes all three research directions. The
      second one demonstrates all the criteria used for evaluating acute leukaemia
      classification. The final set of studies includes 83 investigations, most of
      which focused on enhancing the accuracy and performance of detection and
      classification through proposed methods or systems. Few efforts were made to
      undertake the evaluation issues. According to the final set of articles, three
      groups of articles represented the main research directions in this domain: 56
      articles highlighted the proposed methods, 22 articles involved proposals for
      system development and 5 papers centred on evaluation and comparison. The other
      taxonomy side included 16 main and sub-evaluation and benchmarking criteria. This
      review highlights three serious issues in the evaluation and benchmarking of
      multiclass classification of acute leukaemia, namely, conflicting criteria,
      evaluation criteria and criteria importance. It also determines the weakness of
      benchmarking tools. To solve these issues, multicriteria decision-making (MCDM)
      analysis techniques were proposed as effective recommended solutions in the
      methodological aspect. This methodological aspect involves a proposed decision
      support system based on MCDM for evaluation and benchmarking to select suitable
      multiclass classification models for acute leukaemia. The said support system is
      examined and has three sequential phases. Phase One presents the identification
      procedure and process for establishing a decision matrix based on a crossover of
      evaluation criteria and acute leukaemia multiclass classification models. Phase
      Two describes the decision matrix development for the selection of acute
      leukaemia classification models based on the integrated Best and worst method
      (BWM) and VIKOR. Phase Three entails the validation of the proposed system.

PMID- 30232631
TI  - A porous polyaniline nanotube sorbent for solid-phase extraction of the
      fluorescent reaction product of reactive oxygen species in cells, and its
      determination by HPLC.
AB  - A method is described for extracting and detecting the fluorescent reaction
      product (2',7'-dichlorofluorescein, DCF) that is formed by reaction of reactive
      oxygen species (ROS) with dichlorodihydrofluorescein diacetate (DCFH-DA). DCF is
      extracted by using porous polyaniline nanotubes (PPN) which have a large specific
      surface and pore volume which favor the adsorption capacity. Additional
      attractive features include an appropriate pore size distribution, hydrophobic
      surface, and electron-attracting groups which contribute to DCF adsorption. A
      variety of methods was applied to characterize the morphology of PPN. Under
      optimal conditions and by performing DCF in 0.08-1.0 MUM concentrations, the
      correlation coefficient of the calibration plot is 0.999. The limits of detection
      for standard DCF solutions is 20 nM. Compared with commercial sorbents for solid
      phase extraction (SPE) such as commercially available carbon or Welchrom(r) C18,
      the use of the new sorbent results in better retraction recovery (92%) and longer
      reuse times (30 times). Doxorubicin and X-ray radiation were used to externally
      stimulate the ROS production in HepG2 and Hela cells. ROS was stabled by DCFH-DA
      and quantified by DCF. Following SPE, DCF was detected by HPLC and the
      concentration ROS was calculated. Graphical abstract ?.

PMID- 30232634
TI  - 3D CT cinematic rendering of mycotic aneurysms.
AB  - Mycotic aneurysms are uncommon but emergent conditions in which infection of a
      vessel leads to a contained rupture. Progression to frank rupture, thrombosis,
      distal embolization, and death can occur. The widespread availability of computed
      tomography (CT) and its ability to obtain high-resolution, contrast-enhanced,
      volumetric images rapidly has made it the modality of choice for evaluating
      mycotic aneurysms. Three-dimensional CT visualizations can provide important
      information to surgeons and interventionalists prior to attempting repair of
      these lesions. In this case series, we demonstrate the appearance of mycotic
      aneurysms with the novel 3D CT visualization methodology known as cinematic
      rendering (CR). CR makes use of a more complex lighting model than has previously
      been utilized with other 3D CT techniques, allowing for enhanced surface detail
      and realistic shadowing effects. These features of CR may have utility in
      evaluating mycotic aneurysms and in pre-procedural/pre-operative planning,
      although a prospective study definitively evaluating this has not yet been
      performed.

PMID- 30232636
TI  - Big Sleep: Beyond Propofol Sedation During GI Endoscopy.

PMID- 30232635
TI  - Winged Partially Covered Self-Expandable Metal Stent to Prevent Distal Migration
      in Malignant Gastric Outlet Obstruction.
AB  - BACKGROUND: Through-the-scope implantation of self-expandable metal stents can be
      used for the palliation of malignant gastric outlet obstruction. Although covered
      stents were developed to prevent tumor ingrowth, often seen with uncovered
      stents, migration is still a major problem. Especially, surgical treatment is
      required for some patients if distal migration occurs. AIMS: To evaluate the
      usefulness of the newly designed winged stent that was developed to prevent
      distal stent migration. METHODS: This was a single-center, single-arm,
      retrospective study. A total of 63 inoperable cancer patients with symptomatic
      gastric outlet obstruction were reviewed to evaluate the safety and efficacy of a
      newly designed partially covered self-expandable metal stent with star-shaped
      wing flaps at the proximal end to reduce distal stent migration. RESULTS:
      Technical and clinical successes were achieved in 100% and 87.3% of patients,
      respectively. The gastric outlet obstruction scoring system score significantly
      improved after stent placement (from median 1 to 2, P < 0.001). The median
      duration of stent patency was 147 days (interquartile range 76-201), and median
      duration of overall survival was 176 days (interquartile range 79-325). Stent
      migration was observed in seven patients (11.1%), and restenosis was developed in
      12 patients (19.0%). All cases of migration were proximal, and no distal
      migration was observed. Endoscopic removal of migrated stents was performed
      successfully in all cases. CONCLUSIONS: The newly designed winged stent showed
      feasible efficacy and safety for malignant gastric outlet obstruction.
      Furthermore, it effectively prevented distal stent migration.

PMID- 30232637
TI  - An Additional 30-s Observation of the Right-Sided Colon with Narrow Band Imaging
      Decreases Missed Polyps: A Pilot Study.
AB  - INTRODUCTION: Previous narrow-band imaging (NBI) was dark and reported not to be
      useful for polyp detection. In this study, we analyzed the efficacy of an
      additional 30-s observation of the right-sided colon with the recent bright high
      resolution NBI. METHODS: We enrolled patients undergoing colonoscopy from
      February 2015 to May 2017 in two institutions. All procedures were performed with
      the latest system (EVIS LUCERA ELITE, Olympus). The cecum and ascending colon
      were first observed with white light imaging (WLI) in both the NBI and WLI group.
      Then, the colonoscope was re-inserted, and the cecum and ascending colon were
      observed for an additional 30 s. In this second observation, NBI was performed
      for the first 130 patients in the NBI group and WLI for the next 130 in the WLI
      group. The number of adenoma and sessile serrated polyps (ASPs) in the second
      observation were examined in both groups. According to our initial pilot study,
      the sample size was estimated at 126. RESULTS: In the first observation, the
      number of ASPs was 72 in the NBI group and 72 in the WLI group (p = 1.0). In the
      second observation, the number of ASPs was 23 in the NBI group and 10 in the WLI
      group (p = 0.02). The polyp and adenoma detection rates in the second observation
      were 16.2% and 12.3% in the NBI group and 7.7% (p = 0.03) and 6.2% (p = 0.09) in
      the WLI group. CONCLUSIONS: The additional 30-s observation with recent NBI
      decreased missed polyps in the right-sided colon.

PMID- 30232639
TI  - Prolonged culture of blastocysts after thawing as a tool for improving prediction
      of success.
AB  - PURPOSE: A few years ago, we started to use a new freeze-thaw protocol for the
      frozen embryo transfer cycles. Instead of thawing the embryos 2-4 h prior to the
      transfer, we started thawing the embryos 20-22 h prior to the transfer. The aim
      of this study was to compare the pregnancy rate in cases of embryos that
      continued to develop in the post-thawing culture to that of embryos that did not.
      METHODS: A retrospective cohort study of blastocyst freeze/thaw cycles vitrified
      on day 5, thawed and transferred after 20-22 h in the culture, between January
      2012 and December 2016. RESULTS: A total of 375 patients were included in the
      analysis. Two hundred twenty-eight embryos graded as good, 87 graded as fair, and
      60 graded as poor embryos were transferred. The clinical pregnancy rate (50% vs.
      19.5% vs 3.3% p < 0.01) and the ongoing pregnancy rate (38.5% vs. 13.6% vs 1.7% p
      < 0.01) were higher in cases of good embryo quality compared with fair and poor
      quality embryos, respectively. For good embryos, progressing to a better grade
      during the culture did not change the clinical pregnancy rate (51.3% vs. 46.2% p
      = NS) or the ongoing pregnancy rate (38.5% vs. 37.5% p = NS). For fair embryos,
      progressing to a better grade during the culture resulted in a higher clinical
      pregnancy rate (25.4% vs 9% p = 0.05). CONCLUSIONS: The development of the fair
      embryos in the culture has a highly positive impact on the pregnancy rate and
      this factor should be taken into consideration before deciding how many embryos
      to transfer.

PMID- 30232638
TI  - Questionnaire on Irritable Bowel Syndrome and Symptom Management Among Endurance
      Athletes Is Valid and Reliable.
AB  - BACKGROUND: Gastrointestinal symptoms are reported in a large proportion of
      endurance athletes, with similarities in symptom type and distribution to
      irritable bowel syndrome (IBS). AIMS: The objective of this study was to develop
      and validate a questionnaire to assess IBS diagnoses or fit to IBS diagnostic
      criteria in this population along with nutritional habits, gastrointestinal
      symptoms, and symptom management strategies. METHODS: A 93-item Endurance Athlete
      Questionnaire was developed to address the objective, targeted at American
      endurance athletes completing a marathon, ultra-marathon, half-distance
      triathlon, and/or full-distance triathlon that year. Content validity was
      established by expert reviewers (n = 6), and face validity was evaluated by
      endurance athletes (n = 9). Test-retest reliability was assessed by target
      athletes (n = 51). Participants completed two rounds of the questionnaire,
      separated by 1-2 weeks. Results were analyzed using Pearson and Spearman
      correlations and paired comparisons. RESULTS: Slight modifications in wording and
      three demographic questions were added based on the input of expert and athlete
      reviews. Pearson correlation coefficient of test-retest total questionnaire
      scores was significant at 0.839 (P < 0.001). Paired comparison of individual
      questions found significant differences in 10 of 236 analyzed responses; however,
      these did not affect fit to IBS diagnostic criteria for those without other GI
      diseases/disorders. CONCLUSIONS: The Endurance Athlete Questionnaire proved to be
      a valid and reliable measure of IBS diagnostic criteria, gastrointestinal
      symptoms, nutritional habits, and symptom management strategies among endurance
      athletes. Future implementation will help inform gastroenterologists with
      endurance athlete patients and can elucidate whether certain behaviors could be
      contributing to athlete gastrointestinal symptoms.

PMID- 30232640
TI  - Comprehensive assessment of cryogenic storage risk and quality management
      concerns: best practice guidelines for ART labs.
AB  - Recent publicized events of cryogenic storage tank failures have created
      nationwide concern among infertility patients and patients storing embryos and
      gametes for future use. To assure patient confidence, quality management (QM)
      plans applied by in vitro fertilization (IVF) laboratories need to include a more
      comprehensive focus on the cryostorage of reproductive specimens. The purpose of
      this review is to provide best practice guidelines for the cryogenic storage of
      sperm, oocytes, embryos, and other reproductive tissues (e.g., testicular and
      ovarian tissue, cord blood cells, and stem cells) and recommend a strategy of
      thorough and appropriate quality and risk management procedures aimed to
      alleviate or minimize the consequences from catastrophic events.

PMID- 30232641
TI  - Variants in the CYP19A1 gene can affect in vitro embryo production traits in
      cattle.
AB  - PURPOSE: This study aimed to associate DNA variants in promoter and exon flanking
      regions of the CYP19A1 gene with in vitro embryo production traits in cattle. The
      role of transcription factor binding sites created or lost due to DNA sequence
      variation and their possible effect on gene expression was also evaluated.
      METHODS: We collected date from Gyr dairy oocyte donor cows (Bos taurus indicus)
      at a commercial in vitro embryo production farm and analyzed the genotype
      phenotype association with in vitro production traits. Using Sanger sequencing
      and web-based software, we assessed important CYP19A1 gene regions in oocyte
      donor cows and analyzed the effects of variants on the transcription factor
      binding sites. RESULTS: Two SNP mutations significantly associated with oocyte
      production, oocyte viability, embryo development, and pregnancies were found (T >
      C in the untranslated exon 1 flanking region ([GenBank: AJ250379.1]: rs718446508
      T > C), and a T > C in the 5'-upstream region (1.1 promoter) ([GenBank:
      AC_000167.1]: rs41651668 T > C). Six new transcription factor binding sites were
      created. A binding site for transcription factors associated with the development
      of the placenta and embryo implantation was eliminated due to variations in the
      DNA sequence identified. CONCLUSIONS: The CYP19A1 gene contributes to genetic
      variation of in vitro embryo production traits in cattle. The complexity of the
      physiological phenomena related to estrogen pathways and their influence on
      reproduction in cattle allow indication of the mutations evaluated here as
      possible genetic markers for embryo production traits, which should be validated
      in the next steps of marker-assisted selection.

PMID- 30232642
TI  - Concentration of soluble urokinase plasminogen activator receptor (suPAR) in the
      pre-ovulatory follicular fluid is associated with development of ovarian
      hyperstimulation syndrome during ovarian stimulation.
AB  - PURPOSE: Investigating whether pre-ovulatory follicular fluid (FF) levels of
      selected proteins differ between women who do or do not develop severe ovarian
      hyperstimulation syndrome (OHSS) and evaluate whether they potentially could
      guide a "freeze-all" strategy. METHODS: FF was collected during a randomized
      controlled trial comparing OHSS in antagonist versus agonist protocol including
      1050 women in their first assisted reproductive technology (ART) cycle during
      year 2009-2013. The present sub-study is a matched case-control study comparing
      FF levels of soluble urokinase plasminogen activator receptor (suPAR), C-reactive
      protein, placental growth factor, vascular endothelial growth factor, and
      angiopoietins 1 and 2 in OHSS cases (n = 25, severe OHSS, and >= 15 oocytes),
      high-risk controls (n = 25, no OHSS, and >= 15 oocytes), and low-risk controls (n
      = 25, no OHSS, and 5-8 oocytes). RESULTS: FF level of suPAR differed
      significantly between the three groups (p = 0.018) with mean (SD) levels of 2.3
      (0.4) MUg/L, 2.6 (0.8) MUg/L, and 2.8 (0.6) MUg/L in OHSS cases, high-risk
      controls, and low-risk controls, respectively. Receiver operating characteristic
      curve analysis demonstrated that suPAR levels could predict severe OHSS (AUC
      0.678; 95% CI 0.553-0.803) with a sensitivity of 64% and a specificity of 66%.
      None of the other investigated proteins differed between the three groups or
      between OHSS cases and combined controls. CONCLUSION: The pre-ovulatory FF level
      of suPAR was significantly lower in women developing severe OHSS, indicating that
      the plasminogen activator system could be involved in the pathophysiology of
      OHSS. However, suPAR did not provide a satisfying predictive value for the
      prediction of OHSS.

PMID- 30232643
TI  - Gonadotropin receptor variants are linked to cumulative live birth rate after in
      vitro fertilization.
AB  - PURPOSE: The objective was to investigate if the gonadotropin receptor variants
      N680S (N: asparagine, S: serine, rs6166) in the follicle-stimulating hormone
      receptor (FSHR) and N312S (rs2293275) in the luteinizing hormone/human chorionic
      gonadotropin receptor (LHCGR) predicted cumulative live birth rate after in vitro
      fertilization (IVF). METHODS: A total of 665 women were consecutively enrolled
      for IVF during the period 2007-2016. Inclusion criteria were < 40 years of age,
      body mass index < 30 kg/m2, non-smoking, regular menstruation cycle of 21-35
      days, and bilateral ovaries. A blood sample was drawn for endocrine hormonal
      analysis and for DNA extraction with subsequent genotyping of the FSHR N680S and
      LHCGR N312S polymorphisms. Statistical analyses were done on all completed IVF
      cycles. RESULTS: Women homozygous for S in both receptors combined (4S) had
      significantly higher live birth rate compared to those with other receptor
      variants when combining the first three IVF cycles (OR = 2.00, 95% CI [1.02,
      3.92], p = 0.043). Cumulatively higher chance of live birth rate, during all IVF
      cycles, was also evident (HR = 1.89, 95% CI [1.00, 3.57], p = 0.049).
      CONCLUSIONS: Gonadotropin receptor variants are promising candidates for the
      prediction of the possibility to have a baby to take home after IVF treatment.

PMID- 30232645
TI  - Effect of photobiomodulation on neural differentiation of human umbilical cord
      mesenchymal stem cells.
AB  - Photobiomodulation therapy (PBMT) can enhance the mesenchymal stem cell (MSC)
      proliferation, differentiation, and tissue repair and can therefore be used in
      regenerative medicine. The objective of this study is to investigate the effects
      of photobiomodulation on the directional neural differentiation of human
      umbilical cord mesenchymal stem cells (hUC-MSCs) and provide a theoretical basis
      for neurogenesis. hUC-MSCs were divided into control, inducer, laser, and lasers
      combined with inducer groups. A 635-nm laser and an 808-nm laser delivering
      energy densities from 0 to 10 J/cm2 were used in the study. Normal cerebrospinal
      fluid (CSF) and injured cerebrospinal fluid (iCSF) were used as inducers. The
      groups were continuously induced for 3 days. Cellular proliferation was evaluated
      using MTT. The marker proteins nestin (marker protein of the neural precursor
      cells), NeuN (marker protein of neuron), and GFAP (glial fibrillary acidic
      protein, marker proteins of glial cells) were detected by immunofluorescence and
      western blot. We found that irradiation with 635-nm laser increased cell
      proliferation, and that with 808 nm laser by itself and combined with
      cerebrospinal fluid treatment generated significant neuron-like morphological
      changes in the cells at 72 h. Nestin showed high positive expression at 24 h in
      the 808 nm group. The expression of GFAP increased in the 808-nm combined inducer
      group at 24 h but decreased at 72 h. The expression of neuN protein increased
      only at 72 h in both the 808-nm combined inducer group and inducer group. We
      concluded that 808 nm laser irradiation could help CSF to induce neuronal
      differentiation of hUC-MSCs in early stage and tend to change to neuron rather
      than glial cells.

PMID- 30232644
TI  - A case of primary extraskeletal osteosarcoma of the breast.
AB  - BACKGROUND: Primary sarcomas of the breast are rare and account for less than 1%
      of all primary breast malignancies. We experienced a case of extraskeletal
      osteosarcoma of the breast that had a unique clinical course and remarkable
      findings of mammography and magnetic resonance imaging (MRI). A review of the
      case reports published in the past few decades showed no reports of a case in
      which a calcified lesion was followed up three different times on mammography,
      making this a valuable case report. CASE PRESENTATION: A 52-year-old woman
      noticed a right breast mass and underwent a breast examination. Mammography
      showed a 1.5-cm coarse calcified lesion in the upper outer portion of the right
      breast. Because fine-needle aspiration (FNA) revealed no suspicion of malignancy,
      she was followed up. Sixteen months later, the tumor grew progressively to 4.5 cm
      in size with new calcifications that were fine and irregular in shape and density
      surrounding an enlarged, coarse calcified lesion. Contrast-enhanced magnetic
      resonance imaging (MRI) showed a high signal intensity in the periphery of the
      tumor. Extirpation of the tumor was indicated. The pathological findings were
      extraskeletal osteosarcoma. She underwent additional resection and latissimus
      dorsi flap reconstruction at the Department of Orthopedic Surgery. CONCLUSION:
      The present case suggests that mammography findings of a tumor with coarse
      calcifications that are not typical of benign lesions may be extraskeletal
      osteosarcoma. A diagnosis must be made as early as possible in order to improve
      the prognosis of this disease.

PMID- 30232646
TI  - Photobiomodulation is associated with a decrease in cell viability and migration
      in oral squamous cell carcinoma.
AB  - The treatment of squamous cell carcinoma (SCC) involves surgery, chemotherapy,
      and/or radiotherapy, which can cause mucositis (inflammation of the oral mucosa
      that causes considerable pain and can compromise the continuity of oncological
      treatment). Photobiomodulation (PBM) has been successfully used in the treatment
      of mucositis, but doubts arise regarding the use of laser for areas in which
      tumor cells may remain. In this study, the effect of PBM on the viability,
      mitochondrial activity, proliferation, apoptosis, and migration of cells derived
      from oral SCC was evaluated. SCC9 cells were irradiated with laser (660 and 780
      nm, using 11 dosimetric parameters) and submitted to mitochondrial and caspase 3
      activity tests after 1 and 3 days. Based on the results, cell viability (neutral
      red assay), proliferation (BrdU assay), and migration (scratch-wound assay) were
      evaluated using only the dosimetric parameters recommended for mucositis. Non
      irradiated cells served as the control. The experiments were performed in
      triplicate. The 11 parameters diminished mitochondrial activity and induced tumor
      cell apoptosis. Using the parameters recommended for mucositis, irradiation with
      780 nm (70 mW, 4 J/cm2) proved to be the safest and led to a reduction in cell
      viability, the induction of apoptosis, and a reduction in the migration capacity
      of the tumor cells.

PMID- 30232647
TI  - A hybrid material composed of an amino-functionalized zirconium-based metal
      organic framework and a urea-based porous organic polymer as an efficient sorbent
      for extraction of uranium(VI).
AB  - An amino-functionalized zirconium metal-organic framework was composed with a 3D
      urea-based porous organic polymer to give a hybrid material termed UiO-66
      NH2/urea-POP. The material was characterized by Fourier transform infrared
      spectroscopy, powder X-ray diffraction, scanning electron microscopy, and
      Brunauer-Emmett-Teller surface area measurements. It is shown to be a viable
      sorbent for solid-phase extraction of uranium from water samples. Parameters such
      as the pH value of the sample, amount of adsorbent, type and volume of eluent,
      adsorption and desorption time, and sample volume were optimized. Uranyl ion was
      quantified by using UV-vis spectrophotometry by using 1-(2-pyridyl-azo)-2
      naphthol as the indicator. Figures of merits include (a) a maximum sorption
      capacity of 278 mg g-1; (b) a detection limit of 0.6 MUg L-1; and (c) intra-day
      and inter-day precisions (for n = 5 at a concentration of 100 MUg L-1) of 4.8 and
      1.9%, respectively. The sorbent can be recycled, and no significant change was
      observed in the capacity and repeatability of the sorbent after seven
      extractions. The high surface area, metal-binding sites, and stability of the
      sorbent makes it a most viable tool for efficient and fast extraction and removal
      of uranium. Graphical abstract Schematic of a new porous hybrid solid, referred
      to as UiO-66-NH2/urea-POP. It combines a zirconium-based metal-organic framework
      and a urea-based porous organic polymer. It is shown to be a highly efficient
      sorbent for solid-phase extraction of uranium(VI) prior to its spectrophotometric
      determination.

PMID- 30232648
TI  - Sentinel Lymph Node Biopsy and Completion Lymph Node Dissection for Melanoma.
AB  - OPINION STATEMENT: This review critically evaluates recent trials which have
      challenged the practice of completion lymph node dissection (CLND) for melanoma
      patients diagnosed with regional metastasis by positive sentinel lymph node
      biopsy (SLNB). Two trials in the last 2 years, DeCOG-SLT and MSLT-II, found no
      significant differences in melanoma-specific survival between patients, whether
      they received immediate CLND or observation after positive SLNB, despite
      decreases in nodal recurrence achieved by dissection. These trials together
      disfavor routine CLND in most patients after positive SLNB. However, their
      conclusions are limited by study populations which overall harbored a lower
      burden of SLN disease. Special attention needs to be given to patients who do
      have higher risk disease, with SLN tumor burdens exceeding 1 mm in diameter, for
      whom CLND may remain both prognostic and therapeutic. Current guidelines thus
      recommend either CLND or careful observation after positive SLNB after
      appropriate risk stratification of patients. While a decline in CLND is
      inevitable, treatment of stage III melanoma is witnessing the concurrent rise of
      effective adjuvant therapies. PD-1 inhibitors such as nivolumab, or combination
      BRAF/MEK inhibitors for V600E or K mutant melanoma, which were previously
      available to only trial patients with completely resected stage III disease, are
      now approved for use in patients with positive SLNB alone. Providers are better
      equipped than ever to treat clinically occult, regional metastatic disease with
      SLNB followed by adjuvant therapy for most patients, but should take steps to
      avoid undertreatment of high-risk patients who may proceed to disease relapse or
      progression.

PMID- 30232651
TI  - Aortic valve repair for aortic regurgitation and preoperative echocardiographic
      assessment.
AB  - Aortic valvuloplasty (AVP) has been performed less frequently than mitral
      valvuloplasty. The survival benefit of AVP over replacement has been
      demonstrated. Therefore, standardization of AVP is crucial for its widespread
      adoption. The hemodynamic advantage of AVP of preserving the native aortic valve
      may be one reason for the survival benefit. Recent guidelines still recommend AVP
      in selected cases compared with the less restricted recommendation for mitral
      valvuloplasty, although recent studies have proposed earlier indication for
      surgical intervention. Indication for aortic root replacement is also still
      conservative, especially in Japan. However, more liberal root replacement should
      be recommended for better repair when AVP is indicated. Theoretically, all aortic
      regurgitation lesions can be repaired with acceptable durability. However,
      restricted cusp should be extended by a pericardial patch, which itself has
      emerged as a risk of recurrence. Therefore, indications for aortic regurgitation
      for type III lesions should be determined carefully. Special consideration is
      crucial for bicuspid aortic valve repair; prevention of postoperative stenosis is
      especially important. Arrangement of the commissure position is the most
      important consideration for this purpose, although it remains controversial.
      Therefore, detailed diagnosis is important in planning AVP, and echocardiography
      plays a key role in this process.

PMID- 30232650
TI  - Imaging the Autonomic Nervous System in Parkinson's Disease.
AB  - PURPOSE OF REVIEW: Patients with Parkinson's disease (PD) often display
      gastrointestinal and genitourinary autonomic symptoms years or even decades prior
      to diagnosis. These symptoms are thought to be caused in part by pathological
      alpha-synuclein inclusions in the peripheral autonomic and enteric nervous
      systems. It has been proposed that the initial alpha-synuclein aggregation may in
      some PD patients originate in peripheral nerve terminals and then spread
      centripetally to the spinal cord and brainstem. In vivo imaging methods can
      directly quantify the degeneration of the autonomic nervous system as well as the
      functional consequences such as perturbed motility. Here, we review the
      methodological principles of these imaging techniques and the major findings in
      patients with PD and atypical parkinsonism. RECENT FINDINGS: Loss of sympathetic
      and parasympathetic nerve terminals in PD can be visualized using radiotracer
      imaging, including 123I-MIBG scintigraphy, and 18F-dopamine and 11C-donepezil
      PET. Recently, ultrasonographical studies disclosed reduced diameter of the vagal
      nerves in PD patients. Radiological and radioisotope techniques have demonstrated
      dysmotility and prolonged transit time throughout all subdivisions of the
      gastrointestinal tract in PD. The prevalence of objective dysfunction as measured
      with these imaging methods is often considerably higher compared to the
      prevalence of subjective symptoms experienced by the patients. Degeneration of
      the autonomic nervous system may play a key role in the pathogenesis of PD. In
      vivo imaging techniques provide powerful and noninvasive tools to quantify the
      degree and extent of this degeneration and its functional consequences.

PMID- 30232654
TI  - Nasality in Homosexual Men: A Comparison with Heterosexual Men and Women.
AB  - Several studies reported that pitch and articulation may vary according to a
      person's sexual orientation. The purpose of this study was to investigate whether
      homosexual males also demonstrate differences in nasal resonance compared to
      heterosexual males. Speech samples of 30 self-identified homosexual males, 35
      heterosexual males, and 34 heterosexual females were compared both instrumentally
      and perceptually. Nasalance scores were calculated for the sounds /a/, /i/, /u/,
      and /m/ and for an oronasal, oral, and nasal text. In addition, the Nasality
      Severity Index was determined. Spontaneous speech samples were used for a
      perceptual evaluation of nasal resonance. Neither the nasalance scores nor the
      Nasality Severity Index were significantly different between the homosexual and
      heterosexual males. Heterosexual females, on the other hand, showed significantly
      higher nasalance values for the oronasal and oral text and a significantly lower
      Nasality Severity Index than both the homosexual and the heterosexual males. The
      perceptual judgment revealed no significant differences between the three groups.
      The results of this study suggest that, in contrast to pitch and articulation,
      nasality does not tend to vary with sexual orientation.

PMID- 30232649
TI  - Rethinking Bile Acid Metabolism and Signaling for Type 2 Diabetes Treatment.
AB  - PURPOSE OF REVIEW: Herein, we review the role of FXR and TGR5 in the regulation
      of hepatic bile acid metabolism, with a focus on how our understanding of bile
      acid metabolic regulation by these receptors has evolved in recent years and how
      this improved understanding may facilitate targeting bile acids for type 2
      diabetes treatment. RECENT FINDINGS: Bile acid profile is a key regulator of
      metabolic homeostasis. Inhibition of expression of the enzyme that is required
      for cholic acid synthesis and thus determines bile acid profile, Cyp8b1, may be
      an effective target for type 2 diabetes treatment. FXR and, more recently, TGR5
      have been shown to regulate bile acid metabolism and Cyp8b1 expression and,
      therefore, may provide a mechanism with which to target bile acid profile for
      type 2 diabetes treatment. Inhibition of Cyp8b1 expression is a promising
      therapeutic modality for type 2 diabetes; however, further work is needed to
      fully understand the pathways regulating Cyp8b1 expression.

PMID- 30232652
TI  - Autonomic Regulation of Glucose Homeostasis: a Specific Role for Sympathetic
      Nervous System Activation.
AB  - PURPOSE OF REVIEW: Cardiometabolic disorders such as obesity, metabolic syndrome
      and diabetes are increasingly common and associated with adverse cardiovascular
      outcomes. The mechanisms driving these developments are incompletely understood
      but likely to include autonomic dysregulation. The latest evidence for such a
      role is briefly reviewed here. RECENT FINDINGS: Recent findings highlight the
      relevance of autonomic regulation in glucose metabolism and identify sympathetic
      activation, in concert with parasympathetic withdrawal, as a major contributor to
      the development of metabolic disorders and an important mediator of the
      associated adverse cardiovascular consequences. Methods targeting sympathetic
      overactivity using pharmacological and device-based approaches are available and
      appear as logical additional approaches to curb the burden of metabolic disorders
      and alleviate the associated morbidity from cardiovascular causes. While the
      available data are encouraging, the role of therapeutic inhibition of sympathetic
      overdrive in the prevention of the metabolic disorders and the associated adverse
      outcomes requires adequate testing in properly sized randomised controlled
      trials.

PMID- 30232653
TI  - Improved acid-stress tolerance of Lactococcus lactis NZ9000 and Escherichia coli
      BL21 by overexpression of the anti-acid component recT.
AB  - Acid accumulation caused by carbon metabolism severely affects the fermentation
      performance of microbial cells. Here, different sources of the recT gene involved
      in homologous recombination were functionally overexpressed in Lactococcus lactis
      NZ9000 and Escherichia coli BL21, and their acid-stress tolerances were
      investigated. Our results showed that L. lactis NZ9000 (ERecT and LRecT) strains
      showed 1.4- and 10.4-fold higher survival rates against lactic acid (pH 4.0),
      respectively, and that E. coli BL21 (ERecT) showed 16.7- and 9.4-fold higher
      survival rates than the control strain against lactic acid (pH 3.8) for 40 and 60
      min, respectively. Additionally, we found that recT overexpression in L. lactis
      NZ9000 improved their growth under acid-stress conditions, as well as increased
      salt- and ethanol-stress tolerance and intracellular ATP concentrations in L.
      lactis NZ9000. These findings demonstrated the efficacy of recT overexpression
      for enhancing acid-stress tolerance and provided a promising strategy for
      insertion of anti-acid components in different hosts.

PMID- 30232655
TI  - Two consecutive limb lengthenings with the same PRECICE nail: a technical note.
AB  - PURPOSE: The most significant advance in our time about limb lengthening is the
      magnetic lengthening nail, as the first reports appeared to show good results
      with accurate lengthening rates and good regenerate bone formation. The described
      complication rate is generally low. They avoid external fixation elements, and
      are activated transcutaneously, so the patient's pain and discomfort are reduced
      and the rehabilitation is faster and more effective. The aim of authors is to
      describe a special technical issue of the PRECICE system: the nail can be
      extended inside the patient limb (after the osteotomy), but it also can be
      retracted inside the limb after achieving the bone union. METHODS: The authors
      present a case in which the limb lengthening has been performed in consecutive
      lengthening periods using the same nail. The nail was extended and retracted by
      altering the settings on the external remote control as well as accurately
      setting the rate of distraction. RESULTS: After two consecutive femoral
      lengthening with the same PRECICE nail, the patient no longer has a significant
      lower limb length discrepancy and patient satisfaction was high. During this
      clinical case, we were not confronted with any type of complications. CONCLUSION:
      This technique utilizes the principles and advantages of lengthening over an
      magnetic lengthening nail, avoids the necessity of nail removal and minimizes the
      complication rates and the overall time for complete recovery. LEVEL OF EVIDENCE:
      Level IV.

PMID- 30232656
TI  - LncRNA-135528 inhibits tumor progression by up-regulating CXCL10 through the
      JAK/STAT pathway.
AB  - Spontaneous tumor regression can be observed in many tumors, however, studies
      related to the altered expression of lncRNA in spontaneous glioma regression are
      limited, and the potential contributions of lncRNAs to spontaneous glioma
      regression remain unknown. To investigate the biological roles of lncRNA-135528
      in spontaneous glioma regression. The cDNA fragment of lncRNA-135528 was obtained
      by rapid-amplification of cDNA ends (RACE) technology and cloned into the plvx
      mcmv-zsgreen-puro vector. Additionally, we stably silenced or overexpressed
      lncRNA-135528 in G422 cells by transfecting with siRNA against lncRNA-135528 or
      lncRNA-135528 overexpression plasmid. Then, we examined lncRNA-135528
      overexpressing and lncRNA-135528 silencing on glioma cells and its effects on
      CXCL10 and JAK/STAT pathways. The main findings indicated that lncRNA-135528
      promoted glioma cell apoptosis, inhibited cell proliferation and arrested cell
      cycle progression; the up-regulation of lncRNA135528 led to significantly
      increased CXCL10 levels and the differential expression of mRNA associated with
      JAK/STAT pathway in glioma cells. lncRNA-135528 can inhibit tumor progression by
      up-regulating CXCL10 through the JAK/STAT pathway.

PMID- 30232657
TI  - Do Limitations in the Design of PARADIGM-HF Justify the Slow Real World Uptake of
      Sacubitril/Valsartan (Entresto)?

PMID- 30232658
TI  - Publisher Correction: Exposure to Stress-Dose Steroids and Lethal Septic Shock
      After In-Hospital Cardiac Arrest: Individual Patient Data Reanalysis of Two Prior
      Randomized Clinical Trials that Evaluated the Vasopressin-Steroids-Epinephrine
      Combination Versus Epinephrine Alone.
AB  - The original version of this article unfortunately contained a mistake. In Table
      2, the frequency of Septic Shock reported just below the frequency of "At least 1
      Episode of VAP" actually corresponds to the First (and not the Second) Episode of
      VAP during the postresuscitation period.

PMID- 30232660
TI  - Neurological complications of systemic tumor therapy.
AB  - The treatment of malignant tumors has considerably improved in recent years, and
      also the number of "long term cancer survivors" is increasing.The spectrum of
      anti-tumoral agents is increasing at a fast pace and in addition to conventional
      therapies such as surgery, radiotherapy, and chemotherapy, new drugs with
      entirely new mechanisms are appearing. Side effects of old and new drugs can
      affect the central and peripheral nervous system, the neuromuscular junction, and
      muscle. These side effects often have to be distinguished from other causes and
      need neurological expertise. Although the majority of patients still receive
      conventional therapies, several new strategies such as immune therapies are being
      implemented. These drugs have also drug specific side effects, which do not
      always follow the classical principles of "toxicity."This review focuses on the
      well-known and described side effects of conventional cancer therapies and adds
      new observations on new drugs.

PMID- 30232659
TI  - Establishment of a HEK293 cell line by CRISPR/Cas9-mediated luciferase knock-in
      to study transcriptional regulation of the human SREBP1 gene.
AB  - OBJECTIVES: To establish a HEK293 cell line with a luciferase knock-in reporter
      controlled by the endogenous SREBP1 promoter for investigating transcriptional
      regulation of the SREBP1 gene. RESULTS: PCR confirmed the site-specific
      integration of a single copy of the exogenous luciferase gene into one allele of
      the genome and a 14 bp deletion of the targeted sequence in the other. Luciferase
      activity was directly correlated with the promoter activity of the endogenous
      SREBP1 gene in the HEK293-SREBP1-T2A-luciferase-KI cell line cell line.
      CONCLUSIONS: We successfully generated a novel luciferase knock-in reporter
      system, which will be very useful for studying transcriptional regulation of the
      SREBP1 gene and for screening drugs or chemical molecules that regulate SREBP1
      gene expression.

PMID- 30232661
TI  - Extended use of the modified Berlin Definition based on age-related subgroup
      analysis in pediatric ARDS.
AB  - BACKGROUND: Pediatric acute respiratory distress syndrome (pARDS) is a rare but
      very severe condition. Management of the condition remains a major challenge for
      pediatric intensive care specialists. OBJECTIVE: To perform a descriptive
      assessment of pARDS based on the modified Berlin Definition by using the
      SpO2/FiO2 ratio in order to establish an extended patient registry divided into
      age-related subgroups. METHODS: The data of all children on mechanical
      ventilation for respiratory failure admitted between 2005 and 2012 were reviewed
      retrospectively for this study. The age of patients ranged from newborns >37
      weeks, up to children <18 years. Inclusion criteria were based on the modified
      Berlin Definition of pARDS. The following data were collected: demographic data,
      primary diagnosis, ventilation settings, and use of supportive treatment, in
      addition to mechanical ventilation (inhaled nitric oxide, surfactant,
      corticosteroids, prone positioning, and extracorporeal membrane oxygenation).
      RESULTS: In all, 93 children where included: 35% were newborns, 29% infants, 24%
      toddlers, and 12% school children; 66% were male and 34% were female patients.
      The most common primary diagnosis was viral pneumonia (21%) and 55% of the
      children were diagnosed with severe ARDS. The median duration of stay on the
      pediatric intensive care unit was 16 days (10/27). In total, 66 children (71%)
      had direct lung injury and 18 (19%) had indirect lung injury. More than 80% of
      all children needed more than one supportive care therapy. The overall survival
      rate was 77%. CONCLUSION: This study is a valuable report about pediatric
      patients with ARDS and allows for an important extension of the application of
      the modified Berlin Definition in all age groups.

PMID- 30232662
TI  - Experiences with the Mass Distribution of LPG Stoves in Rural Communities of
      Ghana.
AB  - Household air pollution (HAP) is a leading cause of morbidity and mortality
      worldwide. To limit HAP exposure and environmental degradation from biomass fuel
      use, the Government of Ghana promotes liquefied petroleum gas (LPG) use in rural
      Ghana via the Rural LPG program (RLP). We assessed the experiences of the RLP in
      2015, 2 years after its launch. A mixed methods approach was used involving Focus
      Group Discussions (19) and in-depth interviews (25). In addition, a survey
      questionnaire was administered to elicit socio-demographic characteristics,
      household cooking practices and stove use patterns of 200 randomly selected
      respondents. At about 9 months after LPG acquisition, < 5% of LPG beneficiaries
      used their stoves. Some of the reasons ascribed to the low usage of the LPG
      cookstoves were financial constraints, distance to LPG filling point and fear of
      burns. Community members appreciate the convenience of using LPG. Our results
      underscore a need for innovative funding mechanisms contextualized within an
      overall economic empowerment of rural folks to encourage sustained LPG use. It
      emphasizes the need for innovative accessibility interventions. This could
      include establishing new LPG filling stations in RLP beneficiary districts to
      overcome the barriers to sustained LPG use.

PMID- 30232664
TI  - Association of CD1 and FcgammaR gene polymorphisms with Guillain-Barre syndrome
      susceptibility: a meta-analysis.
AB  - CD1 and immunoglobulin G Fc receptor (FcgammaR) genes have been proposed to be
      involved in the pathogenesis of Guillain-Barre syndrome (GBS). However, results
      of different studies are conflicting. This meta-analysis aimed to systematically
      examine the association between CD1 and FcgammaR gene polymorphisms and GBS. A
      comprehensive literature search through PubMed, EmBase, ScienceDirect, and
      Cochrane Library was performed to identify all eligible studies. The strength of
      association was assessed by pooled odds ratios (ORs) and corresponding 95%
      confidence intervals (95% CI) in allelic, dominant, recessive, homozygous and
      heterozygous genetic models. Four case-control studies about polymorphisms of
      exon 2 in CD1A and CD1E genes and GBS risk and five studies (six cohorts) about
      FcgammaR gene polymorphisms and GBS risk were included in this meta-analysis. The
      association between exon 2 of CD1E gene polymorphism and GBS was marginally
      significant in Caucasians in allelic model (OR = 1.193, 95% CI = 1.001-1.423, P =
      0.049). FcgammaRIIA gene polymorphism was significantly associated with GBS risk
      in Caucasians under allelic model (OR = 1.553, 95% CI = 1.018-2.368, P = 0.041)
      and dominant model (OR = 1.320, 95% CI = 1.027-1.697, P = 0.030). However, no
      significant association was found between polymorphisms in exon 2 of CD1A,
      FcgammaRIIIA and FcgammaRIIIB genes and GBS susceptibility. This meta-analysis
      suggested that FcgammaRIIA gene polymorphism may contribute to GBS risk in
      Caucasians and revealed a certain trend toward significance in the association of
      exon 2 of CD1E gene with GBS in Caucasians. Further studies with larger sample
      size are required to validate these results.

PMID- 30232663
TI  - Association between Cystatin C and SVD in Chinese population.
AB  - Leukoaraiosis is an important clinical feature of cerebral small vessel disease.
      To date, there is no reliable biomarker to reflect the degree of cerebral small
      vessel disease and white matter damage. This study aimed to explore the
      relationship between cystatin C levels and the degree of white matter damage in
      order to assess whether cystatin C could serve as a biomarker for white matter
      damage. We conducted a retrospective analysis of 408 non-critically ill
      hospitalized patients. The included patients underwent related biochemical and
      cerebral magnetic resonance imaging examinations. The magnetic resonance imaging
      results were assessed using the Fazekas scale in fluid attenuation inversion
      recovery imaging. We analyzed the association of each risk factor (sex, age,
      blood glucose, blood lipid, and cystatin C) with the degree of white matter
      damage using univariate logistic and multivariate cumulative odds logistic
      regression (stepwise). Serum cystatin C concentration was closely associated with
      the degree of white matter damage (odds ratio = 2.14), while age, sex, and
      hypertension were associated with selective damage of brain white matter.
      Triglycerides and apolipoprotein A may have a protective effect against white
      matter damage.

PMID- 30232665
TI  - Which cognitive dual-task walking causes most interference on the Timed Up and Go
      test in Parkinson's disease: a controlled study.
AB  - BACKGROUND: There is evidence that cognitive load has a negative effect on the
      gait of patients with Parkinson's disease (PD). However, it is not clear which
      type of cognitive activities are more likely to affect dual-task abilities in
      this patient group. AIMS: To compare the cognitive dual-task abilities in
      patients with PD and control subjects and to analyze the effect of different
      cognitive activities on the walking ability of patients with PD. METHODS: The
      Hoehn and Yahr scale, the Freezing of Gait Questionnaire (FOGQ), Montreal
      Cognitive Assessment (MoCA), and the Functional Reach Test were used to include
      and exclude the patients. The Timed Up and Go (TUG) test was applied under single
      and dual-task conditions. RESULTS: The completion time of TUG was found to be
      increased in the PD group compared with the healthy controls under single- and
      dual-task conditions (p < 0.05). The completion time of TUG was significantly
      increased in dual-task conditions with complex attention activity (serial
      subtractions test) compared with other dual-task conditions in patients with PD
      (p < 0.001). DISCUSSION: The gait performance of both healthy subjects and
      patients with PD was impaired with cognitive activity during walking, and
      patients with PD showed more impairment under different cognitive dual tasks.
      Among the other cognitive tasks, the 'serial sevens' test, a measure of complex
      attention, significantly increased the completion time of TUG. CONCLUSIONS: While
      assessing the dual-task ability of patients with early-stage PD, tasks that
      increase the demand for complex attention seem to be more sensitive to showing
      impaired dual-task ability.

PMID- 30232666
TI  - Characterization and genetic diagnosis of centronuclear myopathies in seven
      Chinese patients.
AB  - Centronuclear myopathies (CNMs) are a group of clinically and genetically
      heterogeneous muscle disorders. Here, we report a cohort of seven CNM patients
      with their clinical, histological, and morphological features. In addition, using
      the next-generation sequencing (NGS) technique (5/7 patients), we identified
      small indels: intronic, exonic, and missense mutations in MTM1, DNM2, and RYR1
      genes. Further genetic studies revealed skewed X-chromosome inactivation in two
      female patients carrying MTM1 mutations. Based on the results of genetic
      analysis, these seven patients were classified as (1) X-linked recessive
      myotubular myopathy (patients 1-3) with MTM1 mutations and mild phenotype, (2)
      the autosomal dominant CNM (patients 4-6) with DNM2 mutations, and (3) the
      autosomal recessive CNM (patient 7) with RYR1 mutations. In all patients,
      histological findings featured a high proportion of fibers with central nuclei.
      Radial arrangement of the sarcoplasmic strands was observed in DNM2-CNM and RYR1
      CNM patients. Muscle magnetic resonance imaging (MRI) revealed a proximal pattern
      of involvement presented in both MTM1-CNM and RYR1-CNM patients. A distal pattern
      of involvement was present in DNM2-CNM patients. Our findings thereby identified
      a number of novel features that expand the reported clinicopathological phenotype
      of CNMs in China.

PMID- 30232667
TI  - Ernst Tromner: beyond the reflex hammer.
AB  - Ernst Tromner (1868-1930) was a German neurologist and psychiatrist at the St.
      Georg Hospital in Hamburg. As clinician and researcher, he contributed to our
      understanding of various fields within neurology including language and speech
      disorders, hypnosis and suggestion, sleep physiology and diseases, leukemia with
      nervous system involvement, gait disorders, metabolic myelopathy, Parkinson's
      disease, organic psychosis, and schizophrenia. However, his main interest was
      muscle reflexes. De facto, Tromner described a variant of the Achilles tendon
      reflex, a modification of the Oppenheim's and Babinski's reflexes, "rediscovered"
      the corneomandibular reflex and described the joint reflexes of the lower
      extremities as well as a muscle stretch reflex of the diaphragm. Moreover,
      Tromner has developed the first sedimentation chamber to assess the cerebrospinal
      fluid as well as the muscle plessimeter and, probably most considerable, the
      reflex hammer which is widely used by neurologists around the globe to date and
      is commonly referred to as the "Tromner hammer." His name has also become
      inextricably linked with the finger flexor reflex, which is commonly known as the
      "Tromner reflex." This article briefly summarizes Professor Ernst Tromner's life
      and his contributions to clinical neurology and psychiatry beyond his most famous
      eponyms, the hammer and the finger flexor reflex.

PMID- 30232668
TI  - Epistaxis as unusual presentation of carotid siphon aneurysms, evolved in
      subacute carotid thrombosis.

PMID- 30232669
TI  - Resolution of unilateral upper limb action tremor after surgical treatment of a
      contralateral frontoparietal arachnoid cyst.
AB  - PURPOSE: Arachnoid cysts (ACs) are cerebrospinal fluid-filled sacs. Although ACs
      are a frequent finding on neuroimaging, most remain asymptomatic during lifetime.
      CASE REPORT: We report a very rare case of a 62-year-old female patient
      presenting with a tremor due to a giant arachnoid cyst, which completely resolved
      after cyst-peritoneal shunting.

PMID- 30232670
TI  - Serum NT-pro CNP levels in epileptic seizure, psychogenic non-epileptic seizure,
      and healthy subjects.
AB  - PURPOSE: Epileptic seizure is the result of uncontrollable neural excitation in
      the brain. The C-type natriuretic peptide is a member of natriuretic peptide
      hormone family and is synthesized by brain and blood vessels in CNS. NT-pro CNP
      is an amino-terminal fragment of C-type natriuretic peptide and is more stable
      compared to its predecessor. In this study, we aimed to evaluate the role of NT
      pro CNP in psychogenic non-epileptic seizures, epileptic seizures, and normal
      subjects. METHODS: Thirty-three patients with epilepsy and 43 patients with
      psychogenic non-epileptic seizures were enrolled in this study. The control group
      consisted of 28 healthy subjects. Post-ictal serum levels of NT-pro CNP were
      acquired from all participants. Statistically significant differences between
      patient groups and controls regarding serum levels of NT-pro CNP were sought.
      RESULTS: NT-pro CNP levels were significantly lower in the epilepsy group than
      the psychogenic non-epileptic seizure group and control group with no significant
      difference between the psychogenic non-epileptic seizure and control group (p <
      0.05). CONCLUSION: Post-ictal serum NT-pro CNP levels were lower in epileptic
      seizures compared to psychogenic non-epileptic seizures as well as healthy
      controls. We think that such a difference is associated with C-type natriuretic
      peptide-related neural mechanisms such as altered microcirculation, increased
      brain-blood barrier permeability, and synaptic stabilization.

PMID- 30232671
TI  - Efficacy of subcutaneous immunoglobulin therapy in a patient with autoimmune
      encephalitis: a case report.

PMID- 30232672
TI  - Atypical clinical manifestations of Miller Fisher syndrome.
AB  - Miller Fisher syndrome (MFS) is characterized by a clinical triad of
      ophthalmoplegia, ataxia, and areflexia, and is closely associated with serum anti
      GQ1b antibody. Although the clinical triad is the cardinal diagnostic clue, a
      variety of other symptoms and signs beyond the triad have been reported. To
      elucidate the frequency and characteristics of atypical clinical manifestations
      of MFS, we recruited 38 patients with MFS and evaluated the symptoms or signs
      beyond the classic triad. Eleven (29%) of 38 patients had atypical clinical
      manifestations of MFS such as headache (n = 6), delayed facial palsy (n = 3),
      divergence insufficiency (n = 2), and taste impairment (n = 2). Headache was
      localized to the periorbital (n = 3), temporal (n = 2), or whole (n = 1) area.
      Only one of them showed bilateral papilledema and an elevated opening pressure in
      cerebrospinal fluid analysis. Delayed facial palsy developed after the other
      signs have reached nadir (n = 1) or started to improve (n = 2), and did not
      follow a pattern of descending paralysis with other cranial neuropathies. Two
      patients showed divergence insufficiency without external ophthalmoplegia, and
      another two had taste impairment over the entire tongue without the other signs
      of facial and glossopharyngeal nerve involvements. Our study shows that
      approximately 30% of MFS patients can have atypical clinical manifestations
      beyond the classic triad. These results reflect the broad clinical spectrum of
      MFS, and might be associated with the presence of additional antiganglioside
      antibodies besides anti-GQ1b in patients with MFS.

PMID- 30232673
TI  - Headache secondary to cervical artery dissections: practice pointers.
AB  - Cervical artery dissections may present with mild and misleading symptoms such as
      a headache or cervical pain. In the absence of early diagnosis and therapy, such
      patients may have a high risk of cerebrovascular events. In order to refine
      evaluation of cervical artery dissections, we report the experience of a single
      center, focusing on clinical findings (e.g., headache and pain-related features
      at onset). From 2012 to 2017, 49 patients with cervical arteries dissections were
      admitted to our institution; 28 out of 49 patients (57%) presented with a
      headache or cervical pain, which were evaluated according to the International
      Classification of Headache Disorders (ICHD-III beta). Item C3a of ICHD-III beta
      ("pain is severe and continuous for days or longer") was present in all patients
      symptomatic for a headache. Another common characteristic was the recent onset,
      with an average (+/- SD) timing from the onset of a headache to the first
      neurologic evaluation of 3 (+/- 2) days (range 1-5). A refined clinical
      evaluation of patients presenting with a headache at the Emergency Department
      could improve the early detection and management of patients with cervical artery
      dissections, in particular when presenting without other associated neurological
      symptoms.

PMID- 30232674
TI  - Genetic Variation of the Kalirin Gene is Associated with ICAS in the Chinese
      Population.
AB  - Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of
      ischemic stroke (IS), especially in recurrent patients. Several studies have
      demonstrated an intimate association between the genetic mutation of the KALRN
      gene and IS. The main aim of this study was to clarify the relationship between
      three single nucleotide polymorphisms (SNPs) of KALRN and ICAS in a northern
      Chinese population and further explore the underlining mechanism. The
      relationship between each SNP and ICAS and the related components were examined
      in five models (co-dominant, dominant, recessive, heterozygous, and additive).
      Multivariate logistic regression models were applied and adjusted for 10,000
      permutation tests. Haplotype regression analysis was performed to determine the
      associations between haplotypes and the severity of ICAS. qRT-PCR was used to
      confirm the mRNA level of Kalirin. SNP rs6438833 of the Kalirin gene in the
      additive model was associated with ICAS (OR = 1.642, 95%CI: 1.129-2.388, PDom =
      0.048). After performing 10,000 permutations, the result showed a trend toward
      statistical significance (Pper = 0.048). Haplotypes of the KALRN gene were not
      significantly associated with ICAS (global significance, p = 0.090). qRT-PCR
      showed that the expression of KALRN 9 in IS patients was almost threefold the
      control group (p < 0.0005). SNPs of the KALRN gene are associated with ICAS in
      the northern Chinese population.

PMID- 30232675
TI  - An Ethical Framework for the Care of Patients with Prolonged Hospitalization
      Following Lung Transplantation.
AB  - The lung allocation score system in the United States and several European
      countries gives more weight to risk of death without transplantation than to
      survival following transplantation. As a result, centers transplant sicker
      patients, leading to increased length of initial hospitalization. The care of
      patients who have accumulated functional deficits or additional organ dysfunction
      during their prolonged stay can be ethically complex. Disagreement occurs between
      the transplant team, patients and families, and non-transplant health care
      professionals over the burdens of ongoing intensive intervention. These cases
      highlight important ethical issues in organ transplantation, including the nature
      and requirements of transplant informed consent, the limits of physician
      prognostication, patient autonomy and decision-making capacity following
      transplant, obligations to organ donors and to other potential recipients, and
      the impact of program metrics on individualized recipient care. We outline
      general ethical principles for the care of lung transplant recipients with
      prolonged hospitalization and give regulatory, research, and patient-centered
      recommendations for these cases.

PMID- 30232676
TI  - Examining the effectiveness of a coordinated perinatal mental health care model
      using an intersectional-feminist perspective.
AB  - Untreated perinatal depression and anxiety are significant public health problems
      that disproportionately affect ethno-racial minorities. The purpose of this study
      was to examine the effectiveness of a coordinated perinatal mental health care
      model, focusing on socially-disadvantaged, ethno-racial minority women, with an
      intersectional-feminist perspective. The treatment model was grounded in
      intersectionality theory with the aim of addressing complex social vulnerability
      factors in the context of perinatal mental health treatment. Participants were 67
      perinatal women (64% African American or Hispanic/Latina) referred by medical
      providers at an urban teaching hospital. Results demonstrated high treatment
      engagement and effectiveness, with 65.9% of participants demonstrating reliable
      improvement in symptoms. Moreover, African American and Hispanic/Latina patients
      had similar treatment outcomes compared to White patients, despite facing greater
      socio-economic disadvantages. Findings indicate that the treatment model may be a
      promising approach to reducing perinatal mental health disparities. Strengths and
      limitations of the study are discussed within the intersectionality framework.

PMID- 30232677
TI  - Metabolism of Docosahexaenoic Acid (DHA) Induces Pyroptosis in BV-2 Microglial
      Cells.
AB  - DHA is one of the most abundant fatty acids in the brain, largely present in
      stores of membrane phospholipids. It is readily released by the action of
      phospholipase A2 and is known to induce anti-inflammatory and neurotrophic
      effects. It is not thought to contribute to proinflammatory processes in the
      brain. In this study, an immortalized murine microglia cell line (BV-2) was used
      to evaluate the effect of DHA on neuroinflammatory cells. Pretreatment of BV-2
      cells with low concentrations of DHA (30 uM) attenuates lipopolysaccharide
      mediated inflammatory cytokine gene expression, consistent with known anti
      inflammatory effects. However, higher (but still physiologically relevant)
      concentrations of DHA (200 uM) induce profound cell swelling and a reduction of
      viability. This is accompanied by increases in the expressions of inflammatory
      cytokine and lipoxygenase genes, activation of caspase-1 activity, and release of
      IL1beta, indicating that cells were undergoing a proinflammatory cell death
      program known as pyroptosis. This process could be attenuated by pharmacological
      inhibition of 12-lipoxygenase (12-LOX, Alox12e), but not by inhibition of 5-LOX
      or 15-LOX. Cumulatively, these data demonstrate that DHA has an anti-inflammatory
      effect on microglial cells, but its metabolism by 12-LOX generates one or more
      products that activate a proinflammatory cell death program.

PMID- 30232678
TI  - Variation of bacterial biodiversity from saline soils and estuary sediments
      present near the Mediterranean Sea coast of Camargue (France).
AB  - Salinity is an important environmental factor influencing microbial community
      composition. To better understand this influence, we determined the bacterial
      communities present in 17 different sites of brackish sediment (underwater) and
      soil (surface) samples from the Camargue region (Rhone river delta) in southern
      France during the fall of 2013 and 2014 using pyrosequencing of the V3-V4 regions
      of the 16S rRNA genes amplified by PCR. This region is known for abundant flora
      and fauna and, though saline, 30% of rice consumed in France is grown here. We
      found that bacterial abundance in 1 g of soil or sediment, calculated by qPCR,
      was higher in sediments than in surface soil samples. Members belonging to the
      Proteobacteria, Bacteroidetes, Chloroflexi and Firmicutes phyla dominated the
      bacterial communities of sediment samples, while members belonging to the
      Proteobacteria, Bacteroidetes, Gemmatimonadetes, Actinobacteria, Firmicutes and
      Acidobacteria phyla dominated the bacterial communities of the soil samples. The
      most abundant bacterial genera present in the saline sediments and soils from the
      Camargue belonged mostly to halophilic and sulphate reducing bacteria, suggesting
      that the Camargue may be a valuable system to investigate saline, yet
      agriculturally productive, sediment and soil microbial ecosystem.

PMID- 30232679
TI  - An update on the taxonomy of the genus Frankia Brunchorst, 1886, 174AL.
AB  - Since the recognition of the name Frankia in the Approved Lists of bacterial
      names (1980), few amendments have been given to the genus description. Successive
      editions of Bergey's Manual of Systematics of Archaea and Bacteria have broadly
      conflicting suprageneric treatments of the genus without any advances for
      subgeneric classification. This review focuses on recent results from
      taxongenomics and phenoarray approaches to the positioning and the structuring of
      the genus Frankia. Based on phylogenomic analyses, Frankia should be considered
      the single member of the family Frankiaceae within the monophyletic order,
      Frankiales. A polyphasic strategy incorporating genome to genome data and
      omniLog(r) phenoarrays, together with classical approaches, has allowed the
      designation and an amended description of a type strain of the type species
      Frankia alni, and the recognition of at least 10 novel species covering symbiotic
      and non symbiotic taxa within the genus. Genome to phenome data will be shortly
      incorporated in the scheme for proposing novel species including those
      recalcitrant to isolation in axenic culture.

PMID- 30232680
TI  - Obstructive sleep apnea in pregnancy: performance of a rapid screening tool.
AB  - PURPOSE: The Sleep Apnea Symptom Score (SASS) has been commonly used to assess
      obstructive sleep apnea (OSA). The aim of this study was to examine the
      psychometric properties of the SASS and the predictive value of SASS
      incorporating bedpartner-reported information in identifying OSA in pregnant
      women. METHODS: A cohort of healthy pregnant women completed the SASS and
      Pittsburgh Sleep Quality Index. Participants underwent overnight laboratory
      polysomnography (PSG) monitoring. Reliability and validity of the SASS were
      evaluated. A multivariable predictive model, incorporating the SASS score along
      with BMI, age, and bedpartner-reported information, was developed to assess the
      risk for OSA (AHI >= 5 events/h). Receiver operating characteristic curves for
      OSA were constructed to evaluate the sensitivity and specificity of the
      predictive model. RESULTS: A total of 126 and 105 participants completed the PSG
      during the first and third trimester, respectively. The SASS demonstrated
      adequate validity and acceptable reliability (Cronbach's alpha = 0.72 during the
      third trimester). When the combined model consisting of SASS, age, BMI, and
      bedpartner-reported information was used, the area under the curve for AHI >= 5
      for the first and third trimester was 0.781 (95%CI 0.648, 0.914) and 0.842 (95%CI
      0.732, 0.952), respectively; the sensitivity/specificity was 76.9%/72.4% and
      82.4%/78.0%, respectively. CONCLUSIONS: The SASS alone has acceptable reliability
      and validity, but limited predictive values. A new tool, combining the SASS and
      other patient characteristics (i.e., age, BMI, and bedpartner-reported snoring
      and breathing pauses), demonstrated improved sensitivity and specificity, and
      thus may have greater utility in clinical practice for predicting OSA in pregnant
      women.

PMID- 30232681
TI  - REM obstructive sleep apnea: risk for adverse health outcomes and novel
      treatments.
AB  - Rapid eye movement (REM) sleep was discovered nearly 60 years ago. This stage of
      sleep accounts for approximately a quarter of total sleep time in healthy adults,
      and it is mostly concentrated in the second half of the sleep period. The
      majority of research on REM sleep has focused on neurocognition. More recently,
      however, there has been a growing interest in understanding whether obstructive
      sleep apnea (OSA) during the two main stages of sleep (REM and non-REM sleep)
      leads to different cardiometabolic and neurocognitive risk. In this review, we
      discuss the growing evidence indicating that OSA during REM sleep is a prevalent
      disorder that is independently associated with adverse cardiovascular, metabolic,
      and neurocognitive outcomes. From a therapeutic standpoint, we discuss
      limitations of continuous positive airway pressure (CPAP) therapy given that 3 or
      4 h of CPAP use from the beginning of the sleep period would leave 75% or 60% of
      obstructive events during REM sleep untreated. We also review potential
      pharmacologic approaches to treating OSA during REM sleep. Undoubtedly, further
      research is needed to establish best treatment strategies in order to effectively
      treat REM OSA. Moreover, it is critical to understand whether treatment of REM
      OSA will translate into better patient outcomes.

PMID- 30232682
TI  - Disease Burden and Treatment Patterns of Psoriasis in Russia: A Real-World
      Patient and Dermatologist Survey.
AB  - INTRODUCTION: Data regarding disease burden and quality of life (QoL) for
      patients with psoriasis from Russia are limited. The objective of this study was
      to describe the demographic and clinical characteristics, comorbidities, and
      treatment patterns of systemic therapy eligible psoriasis patients in Russia in
      order to assess the impact of psoriasis on the QoL and work productivity of the
      patients and to evaluate patient/dermatologist concordance on disease severity,
      signs/symptoms, and satisfaction with psoriasis treatment. METHODS: Data were
      collected by the Growth from Knowledge Disease Atlas global real-world evidence
      programme from nine countries. The data from the Russian population are presented
      here. Adult patients who had a current or prior history of moderate-to-severe
      psoriasis and were receiving prescription treatment at the time of the survey
      were included. Dermatologist-reported data on disease severity, symptoms,
      comorbidities, and treatment as well as patient-reported data on QoL and work
      productivity were collected. Descriptive analysis of the data was conducted.
      Patient/dermatologist concordance was assessed using Cohen's kappa. RESULTS: A
      total of 300 patients from Russia were included. The mean Psoriasis Area and
      Severity Index score was 9.0 and the mean disease duration was 9.9 years. The
      proportion of patients with itch, skin pain, and comorbidities increased as
      current psoriasis severity increased. The disease had a negative impact on
      patients' QoL (mean Dermatology Life Quality Index score: 7.1) and work
      productivity (33.2% drop in work productivity), which further deteriorated as
      disease severity increased. A large proportion of the enrolled patients (60%)
      were treated with topical agents only. Overall, the level of concordance between
      patients and their dermatologists regarding psoriasis severity and satisfaction
      with overall disease control achieved was low. CONCLUSION: Results demonstrate a
      substantial disease burden on psoriasis patients in Russia, despite receiving
      treatment for their psoriasis, as well as low patient/dermatologist concordance
      of views on treatment outcomes. These findings also highlight a need to further
      incorporate the patient's views into treatment decision-making in Russia.
      FUNDING: Novartis Pharma AG, Basel, Switzerland.

PMID- 30232683
TI  - The association of socioeconomic status with receipt of neoadjuvant chemotherapy.
AB  - BACKGROUND: There are advantages to neoadjuvant chemotherapy in operable breast
      cancer, particularly for those with higher-risk cancers, but little is known
      about factors that are associated with the use of neoadjuvant chemotherapy
      outside of clinical trials. We examined whether use of neoadjuvant chemotherapy
      instead of adjuvant chemotherapy varies by nonclinical factors such as patient
      socioeconomic status or rural residence. METHODS: Women diagnosed with breast
      cancer in 2013-2014 at eight medical institutions were surveyed by mail regarding
      their experiences with breast cancer treatment, and this information was linked
      to hospital-based cancer registries. We examined the use of neoadjuvant
      chemotherapy among women with histologically confirmed invasive stage I-III
      breast cancer and used regression models to examine the association of
      socioeconomic status with chemotherapy timing. We also explored potential
      mechanisms for those differences. RESULTS: Over 29% of the chemotherapy sample
      overall received neoadjuvant chemotherapy. Neoadjuvant receipt was lower for
      those with income < $100,000 (AOR 0.56, 95% CI 0.2-0.9) even with adjustment for
      other demographics, stage, and biomarker status, and findings for education and a
      variable for both lowest education and income < $100,000 were similar.
      Rural/urban residence was not associated with neoadjuvant receipt. Differences by
      income in perceptions of the importance of neoadjuvant chemotherapy advantages
      and disadvantages did not appear to explain the differences in use by income.
      CONCLUSIONS: In a multicenter sample of breast cancer patients, lower income was
      strongly associated with less receipt of neoadjuvant chemotherapy. Since patients
      with lower socioeconomic status are more likely to present with later-stage
      disease, this pattern has the potential to contribute to breast cancer outcome
      disparities.

PMID- 30232684
TI  - On farm evaluation of sun-dried Ziziphus spina-christi leaves substitution for
      natural pasture hay on feed intake and body weight change of Bati goat breeds in
      Ethiopia.
AB  - The study was conducted to evaluate the effect of feeding different levels of sun
      dried Ziziphus spina-christi (ZC) leaves on feed intake and live weight gain of
      local male goats. Twenty-five male local breed of goats at 1 year of age (body
      weight; BW = 20.7 +/- 0.72 kg) were randomly allocated to five treatments and
      five replications. Treatments were as follows: T1 (grass hay only; control
      group); T2 (75% grass hay + 25% ZC leaves); T3 (50% grass hay + 50% ZC leaves);
      T4 (25% grass hay + 75% ZC leaves), and T5 (100% ZC leaves). The study lasted for
      90 days. During this period, feed intake, BW change, and average daily gain were
      evaluated. There was a significant difference in total dry matter intake of goats
      fed on different levels of ZC leaves compared with the control group. Mixing of
      the pasture grass hay diet improved (P < 0.05) goats feed intake from 440 to 592
      g/head/day at the minimum proportion of 25% ZC and natural pasture mixture.
      However, there was no significant difference (P > 0.05) in feed intake among the
      supplemented groups (T2-T5) as ZC leaves proportion increased. Goats in the
      control group and in the 25% ZC treatment diet gained 31.4 and 46.7 g, which was
      not different (P > 0.05). The highest average daily BW was gained (P < 0.05) in
      goats supplemented with the highest level (100%) of ZC leaves. T5 (100% ZC leaves
      supplementation) showed a significant increment (P < 0.05) in body weight gain of
      goats over other treatments and the control. Feed conversion ratio was increased
      (P < 0.05) with increased inclusion level of ZC leaves. Goats on supplemented
      treatments 1 and 2; treatments 4 and 5 had no significant difference (P > 0.05)
      in feed conversion efficiency while there was a significant (P < 0.05) difference
      between treatments 2 and 3 diets which had higher (P < 0.05) feed conversion
      ratio than the control groups. Generally, the results of the current study showed
      that supplementation of goats with above 50% level of dried ZC leaves in their
      diet significantly increased feed intake and body weight gain by improving feed
      conversion efficiency of goats.

PMID- 30232685
TI  - The phenotypic relationship between residual intake and gain and other feed
      efficiency traits in Nellore cattle.
AB  - This study aimed to compare feed efficiency measures of Nellore beef cattle on
      different residual intake and gain (RIG) classes. We used data from 610 animals
      weighing on average 236.33 kg and average of 283 days of age from feedlot
      performance tests carried out between 2005 and 2012. Animals were grouped based
      on RIG into three different classes: high RIG (> mean + 0.5 standard deviation
      (SD), most efficient; n = 193), medium RIG (mean +/- 0.5 SD; n = 235), and low
      RIG (< mean - 0.5 SD, least efficient; n = 182). Residual feed intake (RFI),
      residual gain (RG), feed conversion ratio (FCR), feed efficiency (FE), relative
      growth rate (RGR), and Kleiber ratio (KR) of animals in each RIG class were
      compared by Tukey test at 1% of probability. Phenotypic correlations between
      variables were evaluated as well. Animals on high RIG class showed lower dry
      matter intake (P < 0.01) and higher average daily gain (P < 0.01) than low RIG
      animals. Consequently, high RIG animals had lower FCR (P < 0.01) and higher FE (P
      < 0.01) than those animals in low RIG class. The most efficient animals based on
      RIG were also the most efficient animals based on RG and RFI. RIG was negatively
      correlated to dry matter intake (P < 0.01) and FCR (P < 0.01), and a positive
      correlation was found between RIG and FE (P < 0.01). Therefore, RIG appears to be
      a good parameter to select animals with reduced dry matter intake and high
      productive performance.

PMID- 30232686
TI  - Novel approach to discriminate left bundle branch block from nonspecific
      intraventricular conduction delay using pacing-induced functional left bundle
      branch block.
AB  - PURPOSE: Left bundle branch block (LBBB) has a predictive value for response to
      cardiac resynchronization therapy as reported by Zareba et al. (Circulation
      123(10):1061-1072, 2011). However, based on ECG criteria, the discrimination
      between complete LBBB and nonspecific intraventricular conduction delay is
      challenging. We tested the hypothesis that discrimination can be performed using
      standard electrophysiological catheters and a simple stimulation protocol.
      METHODS: Fifty-nine patients were analyzed retrospectively. Patients were divided
      into groups of narrow QRS (n = 20), wide QRS of right bundle branch block (RBBB)
      morphology (n = 14), and wide QRS of LBBB morphology (n = 25). Using a diagnostic
      catheter placed in the coronary sinus, left ventricular activation was assessed
      during intrinsic conduction as well as during right ventricular (RV) stimulation.
      RESULTS: In patients with narrow QRS and RBBB, the Q-LV/QRS ratio was 0.43 +/-
      0.013 (n = 20) and 0.41 +/- 0.026 (n = 14), respectively. In patients with LBBB
      morphology, the Q-LV/QRS split up into a group of patients with normal (0.43 +/-
      0.022, n = 7) and a group with delayed left ventricular activation (0.75 +/-
      0.016, n = 18). By direct comparison of the Q-LV/QRS ratio during intrinsic
      conduction with the Q-LV/QRS ratio during RV pacing leading to a functional LBBB,
      a clear distinction between a group of "true LBBB" and another group of "apparent
      LBBB"/nonspecific intraventricular conduction delay (NICD) could be generated.
      CONCLUSIONS: We present a novel and practical method that might facilitate
      discrimination between patients with apparent LBBB and true LBBB by comparing Q
      LV/QRS ratios during intrinsic activation and during RV stimulation. Although
      this method can already be directly applied, validation by 3D electrical mapping
      and prospective correlation to cardiac resynchronization therapy (CRT) response
      will be required for further translation into clinical practice.

PMID- 30232687
TI  - Feasibility and safety of percutaneous epicardial access for mapping and ablation
      for ventricular arrhythmias in patients on oral anticoagulants.
AB  - PURPOSE: This study aimed to assess the risk of procedure-related complications
      of percutaneous epicardial access (EpiAcc) for radiofrequency catheter ablation
      (RFA) of ventricular arrhythmias (VAs) in patients chronically treated oral
      anticoagulants (OACs) with warfarin compared to those not on OACs. METHODS: We
      analyzed 205 patients (53 +/- 16 years, 155 males) undergoing percutaneous EpiAcc
      as part of an RFA for VAs, and compared the outcome between patients chronically
      on OACs with warfarin (OAC group) and those without (non-OAC group). RESULTS:
      Forty-seven patients (23%) were chronically treated on OACs before their
      procedure. EpiAcc in patients on OAC (OAC group) was not associated with an
      increased risk of cardiac tamponade (11% vs. 6%, p = 0.238) compared to non-OAC
      group, but a higher risk of need for blood transfusion (17% vs. 6%; p = 0.013).
      With respect to the OAC group, the international normalized ratio (INR) on the
      day of the RFA was >= 2.0 in 9 patients (19%) and < 2.0 in the remaining 38
      patients (81%). The rate of all complication and blood transfusion were similar
      between them (11% vs. 21%; p = 0.496, 11% vs. 18%; p = 0.600). CONCLUSION:
      Percutaneous EpiAcc in patients on chronic OAC with warfarin did not
      significantly increase the risk of cardiac tamponade, but was associated with a
      higher risk of need for blood transfusion. EpiACC in patients with an INR > 2.0
      is reasonable in experienced hands when clinical indications are strong.

PMID- 30232688
TI  - Predicting factors of transmural thermal injury after cryoballoon pulmonary vein
      isolation.
AB  - PURPOSE: Transmural thermal injury (TTI), such as esophageal erosion/ulcer and
      periesophageal nerve injury leading to gastric hypomotility, is not rare
      complications associated with pulmonary vein isolation (PVI). However, the
      mechanism and predicting factors of TTI have not yet been fully elucidated with
      second-generation cryoballoon (CB) PVI. METHODS: One hundred ten consecutive
      patients, who underwent CB PVI for atrial fibrillation and received
      esophagogastroduodenoscopy 2 days later, were investigated. The relationships
      between TTI and both clinical and anatomical parameters were examined. We
      measured the following parameters based on the computed tomography data: the
      angle of the left atrial (LA) posterior wall to the descending aorta (Ao) (LA-Ao
      angle); the branching angle of the left inferior pulmonary vein (LIPV) to the
      coronal plane (LIPV angle); and the minimum distance between the LA posterior
      wall and descending Ao enclosing the esophagus (LA-Ao distance). RESULTS: TTIs
      occurred in 19 patients (esophageal erosion in 2 and gastric hypomotility in 17).
      The patients with TTI were significantly older than those without TTI. In the
      anatomical parameters, the LIPV angle was larger and the LA-Ao distance was
      shorter in the TTI (+) group compared to the TTI (-) group. With the multivariate
      logistic regression analysis, the age (odds ratio [OR] 2.148, P = 0.022) and LA
      Ao distance (OR 0.430, P = 0.013) were independent predictors of TTI.
      CONCLUSIONS: The occurrence of TTI in CB PVI was associated with aging,
      suggesting compromised periesophageal circulation, and the anatomical proximities
      between the LA and the descending Ao, which enclose the esophagus.

PMID- 30232689
TI  - The Association Between Park Facilities and Duration of Physical Activity During
      Active Park Visits.
AB  - Public parks provide places for urban residents to obtain physical activity (PA),
      which is associated with numerous health benefits. Adding facilities to existing
      parks could be a cost-effective approach to increase the duration of PA that
      occurs during park visits. Using objectively measured PA and comprehensively
      measured park visit data among an urban community-dwelling sample of adults, we
      tested the association between the variety of park facilities that directly
      support PA and the duration of PA during park visits where any PA occurred. Cross
      classified multilevel models were used to account for the clustering of park
      visits (n = 1553) within individuals (n = 372) and parks (n = 233). Each
      additional different PA facility at a park was independently associated with a
      6.8% longer duration of PA bouts that included light-intensity activity, and an
      8.7% longer duration of moderate to vigorous PA time. Findings from this study
      are consistent with the hypothesis that more PA facilities increase the amount of
      PA that visitors obtain while already active at a park.

PMID- 30232690
TI  - How Do Risk Environment Factors Influence Perpetration of Partner Violence among
      Male Migrant and Non-migrant Market Workers in Central Asia?
AB  - Intimate partner violence (IPV) has emerged as a serious public health issue in
      migrant communities in Central Asia and globally. To date, however, research on
      risk factors associated with male perpetration of IPV among migrants remains
      scant. This study aims to examine risk environment theory-driven factors
      associated with male perpetration of IPV in the prior 6 months. We recruited,
      enrolled, and surveyed a respondent-driven sample of 1342 male market workers in
      Almaty, Kazakhstan, that included 562 (42%) non-migrants defined as Kazakhstan
      citizens who reside in Almaty; 502 (37%) external migrants from Kyrgyzstan,
      Tajikistan, or Uzbekistan; and 278 (21%) internal migrants from other areas of
      Kazakhstan. We conducted multivariate logistic regressions to estimate the
      effects of physical, economic, and political risk environment factors on IPV
      perpetration by migration status after controlling for potentially confounding
      socio-demographic and psychosocial variables. A total of 170 participants (12.7%)
      reported ever perpetrating physical or sexual IPV and 6.7% perpetrated such IPV
      in the prior 6 months. Multiple logistic regression results suggest that the risk
      environment factors of poor living conditions, exposure to political violence,
      and deportation experiences are associated with IPV perpetration among external
      and internal migrants, but not among non-migrants. Food insecurity is associated
      with IPV perpetration among external migrants and non-migrants, but not among
      internal migrants. Homelessness and arrests by police are associated with IPV
      perpetration among internal migrants, but not among external migrants or non
      migrants. These findings underscore the need to consider the unique combination
      of risk environment factors that contribute to male IPV perpetration in the
      design of programs and policies to address IPV perpetration among external and
      internal migrant and non-migrant men in Central Asia.

PMID- 30232691
TI  - Immediate Progressive Disease in Patients with Metastatic Renal Cell Carcinoma
      Treated with Nivolumab: a Multi-Institution Retrospective Study.
AB  - BACKGROUND: Investigations on rapid disease progression in patients with urologic
      malignancies treated with immune checkpoint inhibitors are currently lacking.
      OBJECTIVE: The objective of this study was to assess cases of rapid disease
      progression/immediate development of progressive disease (immediate PD) in
      patients with pretreated metastatic renal cell carcinoma (mRCC) treated with
      nivolumab. PATIENTS AND METHODS: Forty patients were retrospectively evaluated.
      Immediate PD within the initial two cycles of nivolumab therapy was clinically or
      objectively diagnosed. Clinical diagnosis was defined as an acceleration of
      symptoms directly caused by tumor growth or systematic worsening of the general
      condition, such as cachexia. Objective diagnosis was based on imaging evaluation
      using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline
      (version 1.1). RESULTS: Seven patients (17.5%) developed immediate PD. For these
      patients, the median time from the initiation of nivolumab treatment to PD was 14
      days; all seven patients subsequently died from the cancer. Progression-free
      survival (0.66 vs. 10.5 months; p < 0.0001) and overall survival (1.41 months vs.
      not reached; p < 0.0001) were significantly shorter in patients with immediate PD
      than in those without immediate PD. Further, female sex (p = 0.0434), poor
      Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score (p = 0.0263), and
      shorter prior-line time to progression (p = 0.0218) were associated with
      immediate PD. CONCLUSIONS: The development of immediate PD in mRCC patients
      treated with nivolumab can severely worsen patient prognosis. Sex, MSKCC score,
      and prior-line time to progression may be involved in the development of
      immediate PD. Prospective studies are needed to further assess these findings.

PMID- 30232692
TI  - Isolation of Pteropine orthoreovirus from Pteropus vampyrus in Garut, Indonesia.
AB  - Flying foxes belonging to the genus Pteropus are known to be reservoirs of
      zoonotic viruses. In this study, we describe the isolation of Pteropine
      orthoreovirus (PRV) from rectal swab samples of Pteropus vampyrus in Indonesia.
      PRV is an emerging zoonotic respiratory virus that can be transmitted from bats
      to humans. Rectal swabs (n = 91) were screened by PCR for PRV and 10 (11%) were
      positive. Phylogenetic analysis based on nucleotide sequences indicated that the
      S2, S3, S4, M3, L2, and L3 segments of one isolate (Garut-69) were closely
      related to previously isolated strains in Indonesia. The remaining gene segments
      showed both similarity and genetic divergence with other PRV strains, suggesting
      that re-assortment events had occurred. This is the first report of PRV infection
      to P. vampyrus in West Java, Indonesia.

PMID- 30232693
TI  - Recurrent Acute Pancreatitis: Current Concepts in the Diagnosis and Management.
AB  - PURPOSE OF REVIEW: There have been significant developments in the diagnosis,
      clinical approach, and management of patients with recurrent acute pancreatitis
      (RAP) in the last decade. This review systematically summarizes our current
      understanding of RAP. NEW FINDINGS: Gallstones and alcohol are common causes of
      RAP. Non-alcohol non-biliary RAP (nAnB RAP) is a difficult group of patients
      after excluding these two causes because extensive workup is required to
      elucidate the etiology. Idiopathic RAP is diagnosed after excluding all the known
      causes and recurrence is noted to be higher in such patients. Patients with non
      biliary RAP are prone to develop chronic pancreatitis (CP) suggesting a continuum
      from acute to recurrent to chronic pancreatitis. Often, patients destined to
      develop CP present at an earlier stage with RAP. Endoscopic ultrasound and
      magnetic resonance cholangiopancreatography (MRCP) are the investigations of
      choice to detect microlithiasis, choledocholithiasis, ductal abnormalities, peri
      ampullary malignancies, and early changes of chronic pancreatitis. The role of
      pancreas divisum, sphincter of Oddi dysfunction, and anomalous pancreatobiliary
      union in causing RAP is controversial. Genetic testing may be advisable in
      younger patients. CONCLUSION: With a focused approach and appropriate
      investigations, the etiology of RAP can be identified in a significant proportion
      of patients. Therapeutic options are limited and future research is needed to
      improve understanding of the disease.

PMID- 30232695
TI  - Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma.
AB  - Intravenous elotuzumab (EmplicitiTM), a monoclonal antibody targeting the
      signalling lymphocytic activation molecule F7 (SLAMF7) glycoprotein, is approved
      for use in combination with lenalidomide and dexamethasone for the treatment of
      multiple myeloma in previously-treated adult patients. In the pivotal,
      multinational, phase III ELOQUENT-2 trial in adults with relapsed and/or
      refractory multiple myeloma, elotuzumab in combination with lenalidomide and
      dexamethasone significantly prolonged median progression-free survival (PFS) and
      increased overall response rate (ORR; co-primary endpoints) compared with
      lenalidomide and dexamethasone alone. The clinical benefit of elotuzumab was
      maintained over the longer term (<= 4 years' minimum follow-up); final overall
      survival data are awaited. Health-related quality of life was not negatively
      impacted by the addition of elotuzumab. Elotuzumab combination therapy had a
      generally manageable tolerability profile and the most common adverse events
      (AEs) of grade >= 3 severity were haematological (e.g. lymphocytopenia, anaemia,
      thrombocytopenia, neutropenia). Elotuzumab plus lenalidomide and dexamethasone
      extends the treatment options available for the management of relapsed and/or
      refractory multiple myeloma.

PMID- 30232696
TI  - Correction to: Peramivir: A Review in Uncomplicated Influenza.
AB  - Page 1363: The listing of the reviewer names and affiliations, which previously
      read.

PMID- 30232694
TI  - Faecal Occult Blood Point-of-Care Tests.
AB  - BACKGROUND: Early detection of colorectal cancer decreases the risk of mortality.
      Faecal occult blood tests (FOBT) are recognised as a useful tool for colorectal
      cancer screening. These non-invasive, rapid, and easy-to-carry assays are very
      often used as a point-of-care test and for self-testing. On the market, there are
      various types of FOB tests available, including chemical and
      immunochromatographic tests, which are based on different detection methods and
      differ in their sensitivity and specificity. CONCLUSIONS: Clinicians should be
      aware of the causes of false-negative and false-positive test results, which can
      vary depending on the test. Additionally, stool sampling bias may be a source of
      error and must be considered by the clinician. The current FOBT methods are
      subject to various interfering factors; items such as proper preparation of the
      patient prior to testing or the clinician's knowledge of testing limitations are
      key in correct interpreting results. Novel technologies such as FOBT DNA tests,
      micro RNA tests, and biochips equipped with bacteria can indicate bleeding from
      the gastrointestinal tract and improve diagnostics process.

PMID- 30232697
TI  - Exploring the Structural Mechanism of Covalently Bound E3 Ubiquitin Ligase:
      Catalytic or Allosteric Inhibition?
AB  - Covalent inhibition has recently gained a resurgence of interest in several drug
      discovery areas. The expansion of this approach is based on evidence elucidating
      the selectivity and potency of covalent inhibitors when bound to particular amino
      acids of a biological target. The Nedd4-1, an E3 ubiquitin ligase, is
      characterized by two covalent binding sites, of which catalytic Cyscat and
      allosteric Cysallo are enclosed. This enzyme has demonstrated inhibition at both
      the above-mentioned binding sites; however, a detailed molecular understanding of
      the structural mechanism of inhibition upon Cyscat and Cysallo binding remains
      vague. This prompted us to provide the first account of investigating the
      preferential covalent binding mode and the underlying structural and molecular
      dynamic implications. Based on the molecular dynamic analyses, it was evident
      that although both catalytic and allosteric covalent binding led to greater
      stability of the enzyme, a preferential covalent mechanism of inhibition was seen
      in the allosteric-targeted system. This was supported by a more favorable binding
      energy in the allosteric site compared to the catalytic site, in addition to the
      larger number of residue interactions and stabilizing hydrogen bonds occurring in
      the allosteric covalent bound complex. The fundamental dynamic analysis presented
      in this report compliments, as well as adds to previous experimental findings,
      thus leading to a crucial understanding of the structural mechanism by which
      Nedd4-1 is inhibited. The findings from this study may assist in the design of
      more target-specific Nedd4-1 covalent inhibitors exploring the surface-exposed
      cysteine residues.

PMID- 30232698
TI  - Economic Evaluations of Tyrosine Kinase Inhibitors for Patients with Chronic
      Myeloid Leukemia in Middle- and High-Income Countries: A Systematic Review.
AB  - OBJECTIVES: The objective of this systematic review was to conduct a
      comprehensive assessment of economic evaluations of tyrosine kinase inhibitors
      (TKIs) in patients with chronic myeloid leukemia (CML) in middle- and high-income
      countries. METHODS: A literature search was conducted in Embase, MEDLINE (via
      PubMed) and the Cochrane library on March 3, 2018 to identify economic
      evaluations of chronic myeloid leukemia that met the inclusion criteria. Data on
      such parameters as patient characteristics, cost components, and main outcomes
      were extracted from eligible studies. RESULTS: The literature review retrieved
      798 studies, 17 of which fulfilled the eligibility criteria. Eight studies
      included an economic analysis on newly diagnosed patients with CML. Seven studies
      investigated people with CML who were resistant or intolerant to standard-dose
      imatinib. One article focused on chronic phase (CP)-CML patients who experienced
      failure with first-line treatment for interferon-alpha. The last study
      investigated advanced stages of CML patients. Most studies (n = 70.6%) were
      conducted in high-income countries. Only five studies (n = 29.4%) were performed
      in middle-income countries. Most studies used a Markov model. The time horizon
      varied from six months to life-time. CONCLUSIONS: Despite high costs, the
      included studies indicate that imatinib regimens are cost effective in newly
      diagnosed patients with CP-CML. For people with CML who are resistant or
      intolerant to standard-dose imatinib, dasatinib is likely to be a more cost
      effective strategy in middle-income countries. More studies are necessary to
      assess the long-term efficacy and cost effectiveness of novel treatment options.

PMID- 30232699
TI  - Bioequivalence and Pharmacokinetics of Bisoprolol-Amlodipine 5 mg/5 mg
      Combination Tablet versus Bisoprolol 5 mg Tablet and Amlodipine 5 mg Tablet: An
      Open-Label, Randomized, Two-Sequence Crossover Study in Healthy Chinese Subjects.
AB  - BACKGROUND: The pharmacokinetics of bisoprolol and amlodipine administered as a
      fixed-dose combination (FDC) tablet have not been sufficiently studied in healthy
      Chinese subjects to support a medical need for using the FDC in hypertension.
      OBJECTIVE: This study was conducted to compare the pharmacokinetic profiles of
      the bisoprolol-amlodipine FDC tablet with the bisoprolol tablet and amlodipine
      tablet administered concomitantly under both fasting and fed conditions. METHODS:
      An open-label, randomized, two-period, two-sequence crossover study was designed
      under both fasting and fed conditions. The plasma concentrations of bisoprolol
      and amlodipine were analyzed using a validated liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) assay, and the pharmacokinetic parameters of maximum
      concentration (Cmax) and area under the concentration-time curve (AUC) were used
      to evaluate bioequivalence. RESULTS: The point estimate of geometric mean ratios
      of Cmax and AUC from the time of dosing to the last measurable concentration
      (AUCt) for bisoprolol were 97.85% and 99.46% in the fasting state, and 93.87% and
      98.95% in the fed state, respectively. For amlodipine, the geometric mean ratios
      of Cmax and AUCt were 100.03% and 96.76% in the fasting state, and 106.56% and
      103.07% in the fed state. No cases of treatment-emergent adverse events were
      reported during the entire study period. CONCLUSIONS: Bioequivalence was achieved
      for bisoprolol and amlodipine FDC under both fasting and fed conditions, and all
      treatments were safe and well tolerated by all study subjects. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT03226275.

PMID- 30232700
TI  - A new software scheme for scatter correction based on a simple radiographic
      scattering model.
AB  - In common radiography, image contrast is often limited due mainly to scattered x
      rays and noise, decreasing the quantitative usefulness of x-ray images. Several
      scatter reduction methods based on software correction schemes have been
      extensively investigated in an attempt to overcome these difficulties, most of
      which are based on measurement, mathematical-physical modeling, or a combination
      of both. However, those methods require special equipment, system geometry, and
      extra manual work to measure scatter characteristics. In this study, we
      investigated a new software scheme for scatter correction based on a simple
      radiographic scattering model where the intensity of the scattered x-rays was
      directly estimated from a single x-ray image using a weighted l1-norm contextual
      regularization framework. We implemented the proposed algorithm and performed a
      systematic simulation and experiment to demonstrate its viability. We also
      conducted some clinical image studies using patient's image data of breast and L
      spine to verify the clinical effectiveness of the proposed scheme. Our results
      indicate that the degradation of image characteristics by scattered x-rays and
      noise was effectively recovered by using the proposed software scheme, thus
      improving radiographic visibility considerably. Graphical abstract The schematic
      illustrations of scatter suppression methods by using a an antiscatter grid and b
      a scatter estimation algorithm.

PMID- 30232701
TI  - Sudden unexpected death due to Fournier gangrene.
AB  - Fournier gangrene is a rare fulminant necrotizing infection of the skin and soft
      tissue of the perineum that may result in rapid death. We describe the autopsy
      case of a 70-year-old female with uncontrolled diabetes mellitus who was found
      unexpectedly dead in her house where she lived with her dog. Examination of the
      body revelaed a deep necrotic ulceration of the perineum with exposure of the
      underlying deep muscles that was initially misinterpreted by police officers as
      post mortem animal predation. Medicolegal examination and histological and
      microbiological analyses eliminated this hypothesis and the diagnosis of septic
      multiorgan failure due to necrotizing fasciitis was retained as a cause of death.

PMID- 30232702
TI  - Sex determination with morphological characteristics of the skull by using 3D
      modeling techniques in computerized tomography.
AB  - Sex determination is a major area of investigation in forensic anthropology. As
      technology has advanced, imaging methods such as computed tomography and magnetic
      resonance imaging are being investigated as alternatives to conventional forensic
      anthropological research techniques. This study aimed to investigate the
      suitability of three-dimensional (3D) modeling of volumetric cranial computed
      tomography (CCT) images for sex estimation from skull morphology. In this study,
      CCT angiography images from the Department of Radiology 2017 archives were used
      retrospectively, and 3D images were obtained after the reconstruction of 85 cases
      of CCT images. The sex-dependent morphological characteristics of the skull were
      evaluated by three blinded observers and scored on a scale of 1-5 points
      according to the "Standards for Data Collection from Human Skeletal Remains". The
      accurate sex estimation rates of the first, second and third observers were 91.8,
      92.9 and 92.9%, respectively. The rate of accurate sex estimation for males was
      98-100%, while this rate varied between 83.3-86.1% for females. Consistency in
      sex estimation between the three observers was 83.5%, with a Kappa value of 0.763
      (z = 12.2; p = 0.0001*). The glabella was the most effective morphological trait
      used to estimate sex. The results of this study show that sex can be estimated
      from morphological features in volume-rendered CCT 3D images. Thus, sex can be
      estimated by digital images without the need for maceration processes, and the
      transfer of digital data in place of physical material will make it possible to
      gain expert opinions in forensic anthropology.

PMID- 30232703
TI  - Clinical Parameters for Predicting the Survival in Patients with Squamous and Non
      squamous-cell NSCLC Receiving PD-1 Inhibitor Therapy.
AB  - We explored the associations between progression-free survival (PFS) after the
      initiation of PD-1 inhibitor therapy and the clinical parameters in patients with
      NSCLC. We reviewed the clinical data of patients with NSCLC treated with PD-1
      inhibitor. Data of a total of 36 patients, including 16 patients with squamous
      cell NSCLC and 20 patients with non-squamous cell NSCLC were reviewed.
      Multivariate analyses identified EGFR status, C-reactive protein (CRP), and PFS
      following previous therapy as being significantly associated with the PFS after
      initiation of PD-1 inhibitor therapy in patients with NSCLC. In patients with
      squamous cell NSCLC, the blood neutrophil/lymphocyte ratio (NLR), serum lactate
      dehydrogenase (LDH), serum C-reactive protein (CRP), and PFS following previous
      therapy were identified as being significantly associated with the PFS after
      initiation of PD-1 inhibitor therapy. However, none of these associations, except
      for PFS following previous therapy, were found in patients with non-squamous cell
      NSCLC. NLR, LDH and CRP were associated with the PFS after initiation of PD-1
      inhibitor therapy in patients with squamous cell NSCLC, and PFS following
      previous therapy was the common parameter associated with the PFS after
      initiation of PD-1 inhibitor therapy in both squamous-cell NSCLC and non-squamous
      cell NSCLC patients.

PMID- 30232704
TI  - Atypical serious hematochezia and rare imaging feature in gastrointestinal
      tuberculosis.
AB  - A young patient had serious hematochezia for nearly 2 months without obvious
      cause. Abdominal CT images showed rare features such as serious hemorrhage and
      multiple miliary nodules in the small bowel. The colonoscopy showed multiple
      lymphoid follicles in the terminal ileum. The laparotomy showed adverse adhesion
      in the abdominal cavity and multiple miliary noduli in the surfaces of small
      bowel wall. The pathology suggested tuberculosis. This patient received anti-TB
      therapy and the condition improved gradually. There are many variants of GI
      tuberculosis demonstrating uncommon and rare imaging features. It turned to be
      difficult in diagnosis when it showed the rare appearance, such as the great
      amount of intestinal bleeding and multiple noduli in our case. The reason why
      gastrointestinal bleeding might be attributed to the invasiveness of submucosal
      vessels by the tuberculosis bacteria. And the multiple noduli on the bowel wall
      might be the granuloma formation. Therefore, from the experience of our case,
      gastrointestinal tract might also be the first and only involved site, and it may
      cause great amount of bleeding to a life danger, even in young people.

PMID- 30232705
TI  - Chronic intestinal pseudo-obstruction due to al amyloidosis: a case report and
      literature review.
AB  - A 59-year-old woman presented to our hospital with a 6-month history of nausea,
      weight loss, and abdominal distension. Physical examination revealed abdominal
      distension without tenderness, and edema, numbness, and multiple peripheral
      neuropathy in the limbs. Blood test results showed anemia, hypoproteinemia, and
      hypoalbuminemia. Immunoelectrophoresis detected kappa-type Bence-Jones protein in
      both the serum and urine. Bone marrow examination did not reveal an increase of
      plasma cells. Computed tomography showed intestinal distension and retention of
      intestinal contents. No obstructive intestinal lesions were observed. Lower
      gastrointestinal endoscopy showed a decrease in the vascular visibility of the
      rectal mucosa. Histological findings showed amyloid deposition, which was
      positive for amyloid light-chain (AL) kappa. Thus, she was diagnosed with chronic
      intestinal pseudo-obstruction (CIPO) due to gastrointestinal and neurological
      involvement of AL amyloidosis. Her abdominal symptoms were gradually improved by
      the insertion of an ileus tube and medication. Although we recommended
      chemotherapy for stopping her disease progression, she did not want to receive
      it. She died 1 year later because of her pneumonia. We should keep in mind that
      amyloidosis is an important cause of CIPO. Histopathological examination by
      endoscopic biopsy is required for exact diagnosis and appropriate treatment for
      CIPO due to amyloidosis.

PMID- 30232706
TI  - Influence of fiber connectivity in simulations of cardiac biomechanics.
AB  - PURPOSE: Personalized computational simulations of the heart could open up new
      improved approaches to diagnosis and surgery assistance systems. While it is
      fully recognized that myocardial fiber orientation is central for the
      construction of realistic computational models of cardiac electromechanics, the
      role of its overall architecture and connectivity remains unclear. Morphological
      studies show that the distribution of cardiac muscular fibers at the basal ring
      connects epicardium and endocardium. However, computational models simplify their
      distribution and disregard the basal loop. This work explores the influence in
      computational simulations of fiber distribution at different short-axis cuts.
      METHODS: We have used a highly parallelized computational solver to test
      different fiber models of ventricular muscular connectivity. We have considered
      two rule-based mathematical models and an own-designed method preserving basal
      connectivity as observed in experimental data. Simulated cardiac functional
      scores (rotation, torsion and longitudinal shortening) were compared to
      experimental healthy ranges using generalized models (rotation) and Mahalanobis
      distances (shortening, torsion). RESULTS: The probability of rotation was
      significantly lower for ruled-based models [95% CI (0.13, 0.20)] in comparison
      with experimental data [95% CI (0.23, 0.31)]. The Mahalanobis distance for
      experimental data was in the edge of the region enclosing 99% of the healthy
      population. CONCLUSIONS: Cardiac electromechanical simulations of the heart with
      fibers extracted from experimental data produce functional scores closer to
      healthy ranges than rule-based models disregarding architecture connectivity.

PMID- 30232707
TI  - Diet-induced obesity and associated disorders are prevented by natural bioactive
      type 1 fish collagen peptides (Naticol(r)) treatment.
AB  - To fight against metabolic disorders such as insulin resistance, new alimentary
      behaviors are developed. For instance, hyperproteined, gluten-free, or collagen
      enriched diets could be preconized in order to reduce the consequences of
      obesity. In this aim, this study evaluates the potential effects of warm sea fish
      collagen peptides (Naticol(r)) on representative metabolic and inflammatory
      parameters. For that, male C57Bl6/J mice fed with either a chow- (CD) or high-fat
      diet (HFD) were submitted or not to specific collagen peptides in drinking water
      (4 g/kg bw/d) for 20 weeks. Weight, body composition, glucose tolerance, and
      insulin sensitivity were followed up. Effects of fish collagen peptides on
      various blood parameters reflecting the metabolism status were also measured
      (free fatty acids, triglycerides, cholesterol, hormones) together with adipocyte
      inflammation. Results showed that HFD-fed mice supplemented by fish collagen
      peptides exhibited a significant lower increase in body weight as soon as the
      twelfth week of treatment whereas no effect of the peptide was observed in CD fed
      mice. In line with this result, a weaker increase in fat mass in HFD-fed mice
      supplemented with Naticol(r) at both 9 and 18 weeks of treatment was also
      observed. In spite of this resistance to obesity promoted by fish collagen
      peptides treatment, no difference in glucose tolerance was found between groups
      whereas mice treated with Naticol(r) exhibited a lower basal glycemia. Also, even
      if no effect of the treatment on adipocyte lipolysis was found, a decrease of
      inflammatory cytokines was retrieved in collagen-supplemented group arguing for a
      potential better insulin sensitivity. Altogether, these results need to be
      completed but are the first describing a benefic role of warm sea fish collagen
      peptides in a context of metabolic disease paving the route for a potential
      utilization in human obesity-associated disorders.

PMID- 30232709
TI  - [Remission of a complex periodic catatonic syndrome under electroconvulsive
      therapy].
AB  - This article is reporting about a spontaneous occurred catatonic syndrome in a 52
      years old female patients with no prior psychiatric illness record. The catatonia
      followed a severe depressive episode with psychotic symptoms. At the beginning
      additionally to the catatonic-symptoms severe disorientation and memory
      disturbances were prominent in a way it can be seen in neurodegenerative diseases
      like Lewy-Body-Dementia and Creutzfeldt-Jacob-Disease. The patient didn't respond
      on any medication or showed severe side-effects which led to discontinue the
      medication. After applying widespread somatic diagnostics, which has excluded a
      neurodegenerative disease a electroconvulsive therapy was applied. During this
      treatment the patient showed a recurrence of her catatonic symptoms but they
      remitted if there was a too long period between the convulsive treatments. After
      establishing a sufficient period between the convulsive treatments the symptoms
      remitted totally.

PMID- 30232708
TI  - Calgranulin A (S100A8) Immunostaining: A Future Candidate for Risk Assessment in
      Patients with Non-Muscle-Invasive Bladder Cancer (NMIBC).
AB  - INTRODUCTION: There is an urgent need to identify patients with bladder cancer
      (BC) who are at high risk of recurrence or progression. Calgranulin A is a strong
      marker for muscle-invasive or advanced BC and recent studies have shown its
      potential for identifying patients at risk even in non-muscle-invasive bladder
      cancer (NMIBC). The present study examines risks of recurrence and progression
      dependent on immunostaining with calgranulin A in NMIBC. METHODS: Calgranulin A
      protein expression was evaluated through the immunohistochemistry of 158 randomly
      selected, transurethrally resected BC specimens of separate patients (pTa 89, pT1
      69) using tissue microarrays. Kaplan-Meier survival analysis and Cox regression
      were performed to determine whether calgranulin A expression is associated with
      recurrence-free survival (RFS), progression-free survival (PFS), or cancer
      specific survival (CSS). RESULTS: Calgranulin A expression is significantly
      different between pTa and pT1 tumors (p = 0.000, Mann-Whitney U test) and between
      tumor grades (p = 0.015, Kruskal-Wallis test). Kaplan-Meier estimates produced
      significant results for low and high calgranulin A expression concerning RFS [5y
      RFS 70.4 +/- 4.0% vs. 35.9 +/- 12.5%, median RFS not reached (NR) vs. 12.0 +/-
      4.4 month, p = 0.029, log-rank test], PFS (5y-PFS 90.3 +/- 2.7% vs. 51.5 +/-
      14.0%, median PFS NR in both groups, p = 0.000, log-rank test), and CSS (5y-CSS
      92.9 +/- 2.6% vs. 70.7 +/- 12.4%, median CSS NR in both groups, p = 0.005, log
      rank test). Calgranulin A remained an independent factor for RFS (p = 0.024, HR
      2.43) and PFS (p = 0.002, HR 5.92) according to the multivariate Cox regression
      model. CONCLUSIONS: Calgranulin A expression in NMIBC, detected through
      immunohistochemistry, is a promising marker for the identification of NMIBC
      patients at high risk of recurrence and progression.

PMID- 30232710
TI  - CCN2/CTGF binds the small leucine rich proteoglycan protein Tsukushi.
AB  - Extracellular molecules coordinate the multiple signaling pathways
      spatiotemporally to exchange information between cells during development.
      Understanding the regulation of these signal molecule-dependent pathways
      elucidates the mechanism of intercellular crosstalks. CCN2/CTGF is one of the CCN
      family members that binds BMP2, fibronectin, aggrecan, FGFR2 - regulating
      cartilage and bone formation, angiogenesis, wound repair etc. Tsukushi (TSK),
      which belongs to the Small Leucine-Rich Proteoglycan (SLRP) family, binds
      nodal/Vg1/TGF-beta1, BMP4/chordin, Delta, FGF8, Frizzled4, and is involved in the
      early body formation, bone growth, wound healing, retinal stem cell regulation
      etc. These two secreted molecules are expressed in similar tissues and involved
      in several biological events by functioning as extracellular signaling
      modulators. Here, we examine the molecular interaction between CCN2 and TSK
      biochemically. Co-precipitation assay and Surface Plasmon Resonance measurement
      showed their direct binding with the Kd value 15.3 nM. Further, the Solid-phase
      Binding Assay indicated that TSK binds to IGFBP and CT domains of CCN2. Our data
      suggest that CCN2 and TSK exert their function together in the body formation.

PMID- 30232711
TI  - Transcatheter versus surgical aortic valve replacement in low- and intermediate
      risk patients: an updated systematic review and meta-analysis.
AB  - Transcatheter aortic valve replacement (TAVR) has been recognized as a well
      established alternative to surgical aortic valve replacement (SAVR) for
      symptomatic aortic stenosis with high surgical risk. With this updated systematic
      review and meta-analysis, we evaluated TAVR vs. SAVR in low- and intermediate
      risk subjects. Studies comparing TAVR and SAVR in low-risk patients (defined as
      STS <= 8% or EuroSCORE <= 20%) were identified with electronic searches. The
      principal endpoint was all-cause mortality at short term (< 3 months), 1, and 2
      years. Other outcomes of interest were cardiac mortality, neurological events,
      paravalvular leakage (PVL), myocardial infarction (MI), major bleeding, acute
      kidney injury (AKI), vascular complications, and new pacemaker (PM) implantation.
      Seventeen articles including 9805 (4956 TAVR and 4849 SAVR) patients were
      eligible. There was no significant difference in all-cause mortality at short
      term [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.63-1.09], 1 year (OR
      1.01, 95% CI 0.86-1.20) and 2 years (OR 0.86, 95% CI 0.64-1.16) between treatment
      groups. Subgroup analyses stratified by surgical risk score (low-risk subgroup:
      STS < 4% or EuroSCORE < 10%, intermediate-risk subgroup: the others) did not show
      interaction on primary endpoints. Compared to SAVR, TAVR had similar rates of
      neurological events, significantly lower risk of MI and AKI, but higher risk of
      vascular complications, new PM implantation and moderate/severe PVL. In low- and
      intermediate-risk patients, TAVR and SAVR have similar short- and mid-term all
      cause mortality. Compared to SAVR, TAVR carries higher rates of vascular
      complications, PM implantation and moderate/severe PVL, but lower risk of MI and
      AKI.

PMID- 30232713
TI  - Protective effects of Brazilian propolis supplementation on capillary regression
      in the soleus muscle of hindlimb-unloaded rats.
AB  - The protective effects of Brazilian propolis on capillary regression induced by
      chronically neuromuscular inactivity were investigated in rat soleus muscle. Four
      groups of male Wistar rat were used in this study; control (CON), control plus
      Brazilian propolis supplementation (CON + PP), 2-week hindlimb unloading (HU),
      and 2-week hindlimb unloading plus Brazilian propolis supplementation (HU + PP).
      The rats in the CON + PP and HU + PP groups received two oral doses of 500 mg/kg
      Brazilian propolis daily (total daily dose 1000 mg/kg) for 2 weeks. Unloading
      resulted in a decrease in capillary number, luminal diameter, and capillary
      volume, and an increase in the expression of anti-angiogenic factors, such as p53
      and TSP-1, within the soleus muscle. Brazilian propolis supplementation, however,
      prevented these changes in capillary structure due to unloading through the
      stimulation of pro-angiogenic factors and suppression of anti-angiogenic factors.
      These results suggest that Brazilian propolis is a potential non-drug therapeutic
      agent against capillary regression induced by chronic unloading.

PMID- 30232712
TI  - Evaluation of Possible Effects of a Potassium Channel Modulator on Temporal
      Processing by Cochlear Implant Listeners.
AB  - Temporal processing by cochlear implant listeners is degraded and is affected by
      auditory deprivation. The fast-acting Kv3.1 potassium channel is important for
      sustained temporally accurate firing and is also susceptible to deprivation, the
      effects of which can be partially restored in animals by the molecule AUT00063.
      We report the results of a randomised placebo-controlled double-blind study on
      psychophysical tests of the effects of AUT00063 on temporal processing by CI
      listeners. The study measured the upper limit of temporal pitch, gap detection,
      and discrimination of low rates (centred on 120 pps) for monopolar pulse trains
      presented to an apical electrode. The upper limit was measured using the
      optimally efficient midpoint comparison (MPC) pitch-ranking procedure; thresholds
      were obtained for the other two measures using an adaptive procedure. Twelve CI
      users (MedEl and Cochlear) were tested before and after two periods of AUT00063
      or placebo in a within-subject crossover study. No significant differences
      occurred between post-drug and post-placebo conditions. This absence of effect
      occurred despite high test-retest reliability for all three measures, obtained by
      comparing performance on the two baseline visits, and despite the demonstrated
      sensitivity of the measures to modest changes in temporal processing obtained in
      other studies from our laboratory. Hence, we have no evidence that AUT00063
      improves temporal processing for the doses and patient population employed.

PMID- 30232714
TI  - Prevalence and frequency of self-perceived systemic features in people with joint
      hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type.
AB  - Some commonly reported systemic features of joint hypermobility syndrome
      (JHS)/Ehlers-Danlos syndrome hypermobility type (EDS-HT) are absent from
      nosologies due to insufficient validity. The primary aim was to examine the
      hypothesised high prevalence and frequency of orthostatic intolerance, easy
      bruising, and urinary incontinence in adults with JHS/EDS-HT and secondarily to
      determine the association between extent of generalised joint hypermobility (GJH)
      and these systemic features. A cross-sectional cohort study was conducted via
      online recruitment of medically diagnosed JHS/EDS-HT patients. A survey collected
      demographic data and clinical history. A subgroup of participants underwent
      physical testing of GJH using the Beighton score and Lower Limb Assessment Score
      (LLAS). Descriptive analysis was performed on demographic data and self-reported
      non-musculoskeletal systemic features. Correlation of GJH scores and systemic
      features were performed using Spearman's rank correlation. The survey was
      completed by 116 individuals (95% female; 16-68 years) with 57 (93% female) also
      participating in the physical assessment. The most prevalent systemic feature was
      orthostatic intolerance (98%), followed by easy bruising and urinary incontinence
      (97% and 84% respectively). Of those reporting symptoms of orthostatic
      intolerance, easy bruising, and urinary incontinence, 58%, 40%, and 18% described
      them as very highly frequent respectively (frequency > 75%). No significant
      correlations were found between the extent of systemic features and GJH scores as
      measured by either the Beighton score or the LLAS. The high prevalence and
      frequency of the systemic features found in this study, which are omitted in
      diagnostic classification criteria, suggest that further research on their
      diagnostic accuracy is warranted.

PMID- 30232715
TI  - Effects of behavioural risk factors on high-cost users of healthcare: a
      population-based study.
AB  - OBJECTIVES: High-cost users (HCUs) are known to disproportionally incur the
      majority of healthcare utilization costs relative to their counterparts. A number
      of studies have highlighted the detrimental effects of risky health behaviours;
      however, only a few have demonstrated the link to HCUs, a meaningful endpoint for
      program and policy decision-makers. We investigated the association between
      health behaviour risks and downstream high-cost healthcare utilization. METHODS:
      A combined cohort of participants from the Canadian Community Health Survey
      (CCHS) cycles 2005-2009 was linked to future population-based health
      administrative data in Ontario. Using person-centered costing methodology, CCHS
      respondents were ranked according to healthcare utilization costs and categorized
      as ever having HCU status in the 4 years following interview. Logistic regression
      models were used to estimate the association between various health behaviours on
      future HCU status. RESULTS: Models estimated that smoking and physical inactivity
      were associated with a significant increase in the odds of becoming an HCU.
      Compared to individual behaviours, increasing the number of health behaviour
      risks significantly strengthened the odds of becoming an HCU in subsequent years.
      CONCLUSION: The analyses provide evidence that upstream health behaviours affect
      high-cost healthcare utilization. Health behaviours are a meaningful target for
      health promotion programs and policies. These findings can inform decision-makers
      on appropriate behavioural targets for those on an HCU trajectory and promote
      public health efforts to support healthcare system sustainability.

PMID- 30232716
TI  - An encore collaboration between cousins: the Canadian Journal of Public Health
      and the Canadian Society for Epidemiology and Biostatistics : Une autre
      collaboration entre cousins : la Revue canadienne de sante publique et la Societe
      canadienne d'epidemiologie et de biostatistique.

PMID- 30232717
TI  - Equity at all cost-and any price-for research funding in Canada?
AB  - This commentary is in response to the May 2018 announcement by the Canadian
      Institutes of Health Research (CIHR) of a new procedure to ensure fairer access
      to health research funding for participants. As such, all applicants to CIHR's
      funding programs will now be required to complete a five-question questionnaire
      covering the dimensions of gender, age, Indigenous origin, visible minorities,
      and disability. On this basis, CIHR intends to gain a better understanding of the
      performance of its funding programs in terms of equity. In this commentary, we
      wish to question the theoretical and conceptual assumptions of a vision of equity
      framed principally in terms of diversity upstream from the research process as a
      founding principle of more equitable health research in Canada. We draw attention
      to the fact that diversity policies do not necessarily challenge inequity in
      research funding or in research projects. Having established the urgent need for
      action on equity to improve the health of populations, we recall the ethical
      responsibility of research and researchers to better take the various facets of
      equity in research into account. We recommend expanding efforts to understand and
      reflexively address both equity and diversity when considering the performance of
      population health research programs.

PMID- 30232718
TI  - Directional Deep Brain Stimulation.
AB  - Over the last years, deep brain stimulation has seen many technological
      innovations. New electrode designs allowing to direct the current flow not only
      in the vertical but also in the horizontal plane are the most recent. We
      summarize the concept of "directional deep brain stimulation" with its
      opportunities and challenges and the available study data and discuss the use of
      imaging techniques to assist programming deep brain stimulation devices.

PMID- 30232719
TI  - Rovalpituzumab Tesirine: A Novel DLL3-Targeting Antibody-Drug Conjugate.
AB  - Small cell lung cancer (SCLC) comprises about 15% of all cases of lung cancer. In
      recent years, owing to a change in the epidemiology of smoking habits, the
      incidence of the tumor has decreased; however, it remains a significant challenge
      to global health. While the tumor has a favorable initial response to
      chemoradiation, relapse is invariable, and second-line regimens may be
      intolerable given the severity of side effects. For patients with tumors
      resistant to second-line regimens, no current standard regimens exist.
      Rovalpituzumab tesirine is a novel antibody-drug conjugate, targeting delta-like
      protein 3, fundamental in the downstream cellular signaling for proliferation and
      apoptosis. This drug is reported to have shown promise in pre-clinical and phase
      I trials. It appears effective in decreasing tumor burden and is reported to be
      well tolerated, albeit with a significant adverse effect profile. Currently, it
      is being studied as part of initial and subsequent line chemotherapeutic
      regimens; it remains to be seen if this is a viable option in the treatment of
      SCLC. This may add to the agents that can be used against SCLC, and help improve
      outcomes.

PMID- 30232720
TI  - Combined description (morphology with DNA barcode data) of a new quill mite
      Torotrogla paenae n. sp. (Acariformes: Syringophilidae) parasitising the Kalahari
      scrub-robin Cercotrichas paena (Smith) (Passeriformes: Muscicapidae) in Namibia.
AB  - A new quill mite species Torotrogla paenae n. sp. (Acariformes: Syringophilidae)
      parasitising the Kalahari scrub-robin Cercotrichas paena (Smith) (Passeriformes:
      Muscicapidae) in Namibia is described based on the external morphology and DNA
      barcode data (the mitochondrial cytochrome c oxidase subunit 1 sequences, cox1).
      Females of T. paenae n. sp. morphologically differ from the most similar species
      T. lusciniae Skoracki, 2004 by the total body length (780-830 vs 645-715 um in T.
      lusciniae) and the presence of hysteronotal shields (vs absence), apunctate
      propodonotal and pygidial shields (vs punctate), apunctate coxal fields (vs
      punctate), the fan-like setae p' and p" of legs III-IV provided with c.10 tines
      (vs 14-15) and the length of setae si (140-180 vs 190-210 um) and se (160-185 vs
      210-225 um). The male of T. paenae n. sp. morphologically differs from T.
      lusciniae by the lateral branch of peritremes composed of 4 chambers (vs 7-8
      chambers) and lengths of setae ve (45 vs 70-75 um) and se (120 vs 165 um).

PMID- 30232723
TI  - Short- and Mid-term Outcomes of 527 One Anastomosis Gastric Bypass/Mini-Gastric
      Bypass (OAGB/MGB) Operations: Retrospective Study.
AB  - BACKGROUND: One anastomosis gastric bypass/mini-gastric bypass (OAGB/MGB) is
      considered an alternative option in metabolic and bariatric surgery. The aim of
      this study was to evaluate the safety, efficacy and postoperative challenges of
      OAGB/MGB as a new procedure. METHODS: We performed 519 primary MGBs and 8
      additional second-stage MGBs during 2014-2018. The data were collected from
      patients' notes as well as the surgeons' prospective data sheets. Two senior
      surgeons performed the operations. The ultimate primary measures were assessment
      of the safety and management of the complications. The secondary outcomes were
      excess weight loss and resolution of the comorbidities. RESULTS: The type 2
      diabetes mellitus (T2DM) remission rate was 83% and 70% over 1 and 3 years,
      respectively (HBA1C < 6.5%). Weight loss was 28-152 kg (SD 23.11). Excess weight
      loss ranged from 41 to 125%. Hypertension resolution was 61%, 58% and 58% in the
      first, second and third years, respectively. Ninety-nine per cent of sleep apnoea
      patients improved symptomatically and went off the continuous positive airway
      pressure (CPAP) machine. Two (0.37%) patients developed diarrhoea, cured by
      shortening the afferent biliopancreatic limb (BPL). Eight (1.5%) stomal ulcers
      were reported. Two patients (0.37%) developed deranged liver function, revised by
      shortening the BPL in one patient and a reversal in the second patient. The mean
      follow-up was 2.5 years. Mortality was zero. CONCLUSIONS: This is the largest UK
      OAGB/MGB study to date showing safety and acceptable results for metabolic
      syndrome and obesity problems. OAGB/MGB revisional options are rectifying the
      morbidity and no mortality.

PMID- 30232721
TI  - Efficacy and safety of low-intensity shock wave therapy in penile rehabilitation
      post nerve-sparing radical cystoprostatectomy: a randomized controlled trial.
AB  - AIM: To evaluate the role of low-intensity extra corporeal shock wave therapy (LI
      ESWT) in penile rehabilitation (PR) post nerve-sparing radical cystoprostatectomy
      (NS-RCP). MATERIALS AND METHODS: This study included 152 sexually active men with
      muscle invasive bladder cancer. After bilateral NS-RCP with orthotopic diversion
      by a single expert surgeon between June 2014 and July 2016, 128 patients were
      available categorized into three groups: LI-ESWT group (42 patients),
      phosphodiesterase type-5 inhibitors (PDE5i) group (43 patients), and control
      group (43 patients). RESULTS: Mean age was 53.2 +/- 6.5 years. Mean +/- SD follow
      up period was 21 +/- 8 months. During first follow-up FU1, all patients of the
      three groups had insufficient erection for vaginal penetration; with decrease of
      preoperative IIEF-EF mean score from 27.9 to 6.9. Potency recovery rates at 9
      months were 76.2%, 79.1%, and 60.5% in LI-ESWT, PDE5i, and control groups,
      respectively. There was statistically significant increase in IIEF-EF and EHS
      scores during all follow-up periods in all the study groups (p < 0.001). However,
      there was no significant difference between the three groups during all follow-up
      periods. Statistical evaluation showed no significant difference in continence
      and oncological outcomes during all follow-up points among the three groups (p =
      0.55 and 0.07, respectively). CONCLUSIONS: During last follow-up, 16% more
      patients in LI-ESWT group had recovery of potency as compared to the control
      group. Although the difference is not statistically significant, but of clinical
      importance. LI-ESWT is safe as oral PDE5i in penile rehabilitation post nerve
      sparing radical cystoprostatectomy.

PMID- 30232722
TI  - Is there a relationship between phosphodiesterase type 5 inhibitors and
      biochemical recurrence after radical prostatectomy: a systematic review and meta
      analysis.
AB  - PURPOSE: Conduct a systematic review and meta-analysis of studies to evaluate the
      association between the use of PDE5I and biochemical recurrence (BCR) after
      radical prostatectomy (RP). METHODS: We searched Embase (from 1996 to Feb 2018),
      PubMed (from 1996 to Feb 2018), and Cochrane library (from 1999 to Feb 2018),
      then manually searched the reference lists of key retrieved articles. Original
      studies that reported the risk of postoperative BCR for PDE5I users, as compared
      with non-PDE5I users, were included. Data including the characteristic of
      participants, the risk of BCR after RP and key criteria of study quality were
      collected. The pooled relative risks (RRs) were calculated with random-effects
      model. RESULTS: A total of 5 cohort studies and 1 case-control study were
      conducted for data analysis (a total of 17752 participants). Only 1 cohort study
      reported adjusted RR greater than 1 (range for all derived RRs, 0.7-1.47). The
      meta-analysis revealed that the PDE5I users had no higher risk of BCR after RP
      (RR = 1.04, 95% confidence interval [CI], 0.79-1.36). Sensitivity analysis showed
      that the remaining pooled RR and 95% CI were not changed significantly by
      omitting each study. In addition, the 5-year BCR rate had no significant
      difference between PDE5I users and non-PDE5I users. CONCLUSIONS: Our meta
      analysis indicated that PDE5I treatment in men following RP did not increase the
      risk of BCR. The results preliminarily suggested that the use of PDE5I for
      erectile dysfunction after RP was oncologically safe. Nevertheless, more large
      sample cohort studies are needed to validate this conclusion.

PMID- 30232724
TI  - Acute Intestinal Obstruction Due to Internal Hernia After Abdominal
      Dermolipectomy.

PMID- 30232725
TI  - Type 2 Diabetes Remission and Control in Overweight and in Mildly Obese Diabetic
      Patients at Long-Term Follow-Up After Biliopancreatic Diversion.
AB  - BACKGROUND: In severely obese patients with type 2 diabetes (T2DM), the metabolic
      benefits after biliopancreatic diversion (BPD) are due to mechanisms independent
      of weight loss. Therefore, the anti-diabetic effect of BPD in overweight or
      mildly obese T2DM patients was investigated. METHODS: Ninety T2DM patients with
      BMI 25-35 underwent BPD and were evaluated 1 and 5 years after the operation
      (follow-up rate 100 and 83%, respectively). RESULTS: T2DM control (Hb1Ac < 7%)
      and remission (Hb1Ac < 6 without antidiabetics) was observed in 86.6 and 65% of
      cases at 1 year and 64.0% and 26.5% at 5 years, respectively. The long-term T2DM
      remission was predicted by baseline BMI value. Both before BPD and throughout the
      follow-up period, HOMA values were similar in the metabolically successful and
      unsuccessful subjects, while C-peptide normalized for FBG value as a marker of
      beta cell mass and insulin secretion increased progressively only in the former
      from 1.06 +/- 0.64 to 1.44 +/- 1.08 mcg/l ml/dl-1 * 100 (p < 0.002). CONCLUSIONS:
      In T2DM patients with BMI of 25-35, a positive metabolic outcome is less frequent
      than in their counterparts with morbid obesity. In T2DM overweight patients, in
      spite of a short-term normalization of FBG and HbA1c levels and a well-sustained
      increase of insulin sensitivity, a long-term T2DM relapse occurs in the majority
      of the cases. While the surgically obtained decrease in insulin resistance leads
      to T2DM control in half of the patients, the increase in insulin secretion is
      mandatory for T2DM stable remission.

PMID- 30232726
TI  - Agreement Between Body Composition Assessed by Bioelectrical Impedance Analysis
      and Doubly Labeled Water in Obese Women Submitted to Bariatric Surgery : Body
      Composition, BIA, and DLW.
AB  - INTRODUCTION: Bariatric surgery has a significant influence on body composition
      (BC), which should be monitored. However, there is a need to recommend low-cost
      practical methods, with good estimation of BC for class III obese and/or
      bariatric patients. OBJECTIVE: The aim of this study was to determine accuracy
      and agreement between BC assessed by direct segmental multifrequency
      bioelectrical impedance analysis (DSM-BIA) and doubly labeled water (DLW) as
      reference method. MATERIAL AND METHODS: Twenty class III obese women (age 29.3 +/
      5.1 years; body mass index 44.8 +/- 2.4 kg/m2) underwent Roux-en-Y gastric
      bypass surgery. BC (fat mass [FM], fat-free mass [FFM], and total body water
      [TBW]) was assessed by InBody 230 and DLW in the following periods: before and 6
      and 12 months after surgery. Accuracy between the methods was evaluated by the
      bias and root mean square error. Pearson's correlation, concordance correlation
      coefficient (CCC), and Bland-Altman method were used to evaluate agreement
      between the methods. RESULTS: Correlations were significant (p < 0.001) and CCC
      was good/excellent between both methods for the evaluation of FM (r = 0.84-0.92,
      CCC = 0.84-0.95), FFM (r = 0.73-0.90, CCC = 0.68-0.80), and TBW (r = 0.76-0.91,
      CCC = 0.72-0.81) before and after bariatric surgery. In addition, no significant
      bias was observed between DSM-BIA and DLW for FM (mean error [ME] = - 1.40 to
      0.06 kg), FFM (ME = 0.91-1.86 kg), and TBW (ME = 0.71-1.24 kg) measurements.
      CONCLUSION: The DSM-BIA was able to estimate the BC of class III obese women
      submitted to bariatric surgery with values consistent with those of the DLW
      method.

PMID- 30232727
TI  - Influence of Streptococcus mitis and Streptococcus sanguinis on virulence of
      Candida albicans: in vitro and in vivo studies.
AB  - The aim was to evaluate in vitro possible interactions, gene expression, and
      biofilm formation in species of Candida albicans, Streptococcus mitis, and
      Streptococcus sanguinis and their in vivo pathogenicity. The in vitro analysis
      evaluated the effects of S. mitis and S. sanguinis on C. albicans's biofilm
      formation by CFU count, filamentation capacity, and adhesion (ALS1, ALS3, HWP1)
      and transcriptional regulatory gene (BCR1, CPH1, EFG1) expression. In vivo
      studies evaluated the pathogenicity of the interaction of the microorganisms on
      Galleria mellonella, with analyses of the CFU per milliliter count and
      filamentation. In vitro results indicated that there was an observed decrease in
      CFU (79.4-71.5%) in multi-species biofilms. The interaction with S. mitis
      inhibited filamentation, which seems to increase its virulence factor with over
      expression of genes ALS1, ALS3, and HWP1 as well the interaction with S.
      sanguinis as ALS3 and HWP1. S. mitis upregulated BRC1, CPH1, and EFG1. The
      histological images of in vivo study indicate an increase in the filamentation of
      C. albicans when in interaction with the other species. It was concluded that S.
      mitis interaction suggests increased virulence factors of C. albicans, with
      periods of lower virulence and proto-cooperation in the interaction with S.
      sanguinis.

PMID- 30232728
TI  - Neonatal calf meningitis associated with Streptococcus gallolyticus subsp.
      gallolyticus.
AB  - Here, we report a case of neonatal calf meningitis due to Streptococcus
      gallolyticus subsp. gallolyticus (SGG). Clinical, pathological and
      microbiological findings were evaluated. API Strep, 16S rRNA gene sequencing,
      rpoB gene sequencing and sodA gene sequencing were used for the complete
      identification of SGG. This is the first documented report of neonatal calf
      meningitis due to SGG in veterinary medicine.

PMID- 30232730
TI  - Aerobic Exercise Prevents Insulin Resistance Through the Regulation of miR
      492/Resistin Axis in Aortic Endothelium.
AB  - Previously, we found that miR-492 delayed the progression of atherosclerosis (AS)
      by acting as an up-stream regulator of resistin. Therefore, we hypothesized that
      the anti-atherogenic effects of exercise are related to miR-492-mediated
      downregulation of resistin and repair of endothelial injury. In this study, we
      investigated the effects of the miR-492/resistin axis on improving endothelial
      injury in ApoE-/- mice (ApoE-deficient/knockout in C57BL/6 mice) through swimming
      exercises. Our results showed that the severity of AS and insulin resistance (IR)
      in these mice were significantly reduced by swimming exercises. In addition, miR
      492 expression in the aortic endothelium of ApoE-/- mice was decreased, in
      addition to increased levels of resistin. Interestingly, swimming exercises
      increased miR-492 expression while decreasing that of resistin. Taken together,
      swimming exercises delayed the progression of AS, possibly by upregulating miR
      492 and downregulating resistin in aortic endothelium. Therefore, exercises
      modulated glucose and lipid metabolism, alleviated endothelial IR, and repaired
      endothelial injury.

PMID- 30232729
TI  - Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes Promotes Repair
      in Ischemic Myocardium.
AB  - Our previous study demonstrated the beneficial effects of exosomes secreted by
      cardiac mesenchymal stem cells (C-MSC-Exo) in protecting acute ischemic
      myocardium from reperfusion injury. Here, we investigated the effect of exosomes
      from C-MSC on angiogenesis in ischemic myocardium. We intramyocardially injected
      C-MSC-Exo or PBS into the infarct border zone after induction of acute mouse
      myocardial infarction (MI). We observed that hearts treated with C-MSC-Exo
      exhibit improved cardiac function compared to control hearts treated with PBS at
      one month after MI. Capillary density and Ki67-postive cells were significantly
      higher following treatment with C-MSC-Exo as compared with PBS. Moreover, C-MSC
      Exo treatment increased cardiomyocyte proliferation in infarcted hearts. In
      conclusion, intramyocardial delivery of C-MSC-Exo after myocardial infarction
      enhances cardiac angiogenesis, promotes cardiomyocyte proliferation, and
      preserves heart function. C-MSC-Exo constitute a novel form of cell-free therapy
      for cardiac repair.

PMID- 30232732
TI  - Sequence specific 1H, 13C and 15N resonance assignments of the C-terminal domain
      of human gammaS-crystallin.
AB  - The high solubility and stability of crystallins present in the human eye lens
      maintains its transparency and refractive index with negligible protein turnover.
      Monomeric gamma-crystallins and oligomeric beta-crystallins are made up of highly
      homologous double Greek key domains. These domains are symmetric and possess
      higher stability as a result of the complex topology of individual Greek key
      motifs. gammaS-crystallin is one of the most abundant structural betagamma
      crystallins present in the human eye lens. In order to understand the structural
      stability of individual domains of human gammaS-crystallin in isolation vis-a-vis
      full length protein, we set out to structurally characterize its C-terminal
      domain (abbreviated hereafter as gammaS-CTD) by solution NMR. In this direction,
      we have cloned, over-expressed, isolated and purified the gammaS-CTD. The 2D [15N
      1H] HSQC recorded with uniformly 13C/15N labeled gammaS-CTD showed a highly
      dispersed spectrum indicating the protein to adopt an ordered conformation. In
      this paper, we report almost complete sequence-specific 1H, 13C and 15N resonance
      assignments of gammaS-CTD using a suite of heteronuclear 3D NMR experiments.

PMID- 30232731
TI  - Endovascular repair of popliteal artery aneurysms: an Italian multicenter study.
AB  - PURPOSE: The aim of our study is to assess the effectiveness of popliteal artery
      aneurysm (PAA) endovascular treatment. BASIC PROCEDURES: We retrospectively
      evaluated 48 high-surgical-risk patients that presented at our three departments
      with evidence of popliteal artery aneurysms, both symptomatic and asymptomatic,
      and were therefore treated by deployment of stent graft. Immediate technical
      success was 100%. No periprocedural complications occurred. MAIN FINDINGS: During
      a mean follow-up of 24.5 months (range 6-72), 12/48 occlusions of stent graft
      occurred, five of which occurred in the first 30 days after the procedure while
      other seven occurred during long-term follow-up. Primary stent patency rate was
      70.8% and secondary stent patency rate was 89.6% at 1 year. No limb amputation
      was witnessed. CONCLUSIONS: According to our experience, endovascular approach
      appeared as an effective treatment for popliteal artery aneurysms, as it appeared
      affected by a low rate of peri- and post-procedural complications. It could be
      proposed as treatment of choice in patients with high surgical risk.

PMID- 30232733
TI  - Backbone 1H, 13C, and 15N resonance assignments of deubiquitinase A in non
      phosphorylated and phosphorylated forms.
AB  - Ubiquitination is one of the most prevalent forms of post-translational
      modifications that are important for regulating many cellular processes in
      eukaryotes. Deubiquitinases are proteases that hydrolyze the isopeptide or
      peptide bonds formed between ubiquitin and the target proteins or within a
      polyubiquitin chain. Deubiquitinase A (DUBA) is a deubiquitinase known to be a
      negative regulator of innate immune responses in humans by suppressing production
      of type I interferons (INF-I). Excess INF-I production has been associated with
      autoimmune diseases. Phosphorylation of a single serine residue at position 177
      is essential for the protease activity of DUBA. The structural and mechanistic
      basis of DUBA activation by phosphorylation and substrate specificity is not well
      understood. Here, we report the backbone resonance assignments of the isoform 2
      of DUBA in both non-phosphorylated and phosphorylated forms. The reported
      assignments form the basis for future NMR studies on the structural and dynamical
      properties of both active and inactive forms of DUBA.

PMID- 30232734
TI  - Comparing the Effects of Additives on Protein Analysis Between Desorption
      Electrospray (DESI) and Electrospray Ionization (ESI).
AB  - It is frequently said that DESI-MS follows a similar ionization mechanism as ESI
      because of similarities usually observed in their respective mass spectra.
      However, practical use of DESI-MS for protein analysis is limited to proteins
      with lower molecular weights (< 25 kDa) due to a mass-dependent loss in signal
      intensity. Here we investigated commonly used volatile acids and their ammonium
      salt buffers for DESI-MS analysis of protein. We noticed that, surprisingly, some
      additives influence the analysis differently in DESI compared to ESI. Improved
      signal intensities with both DESI and ESI were obtained when acetic and formic
      acid were added into aqueous methanol spray solvents with both DESI and ESI. On
      the other hand, while with ESI the addition of ammonium salts into spray
      solutions strongly reduced both signal and S/N, with DESI signal intensities and
      S/N were improved dramatically. Ammonium bicarbonate when used with DESI reduced
      the total amount of adduction and delivered excellent signal-to-noise ratios with
      high intensity; however, it also denatures protein. When native state protein
      mass spectra are preferred, ammonium acetate would also deliver reasonable adduct
      removal and improved S/N. The amount of total adduction of individual adducting
      species and of all species could not be correlated with differences in either
      solutions pH values or with proton affinities of the anions. An obvious
      difference between DESI and ESI mass spectrometry is the effects of protein
      solubility during droplet pickup (desorption), but differences in the sizes,
      velocities, and composition of ionizing droplets were also discussed as important
      factors. Graphical Abstract ?.

PMID- 30232736
TI  - Correction to: Cost-Effectiveness Analysis of Single-Use EEG Cup Electrodes
      Compared with Reusable EEG Cup Electrodes.
AB  - In the Results section of the abstract, the second sentence which previously
      read.

PMID- 30232737
TI  - In-flight cardiac arrest and in-flight cardiopulmonary resuscitation during
      commercial air travel: consensus statement and supplementary treatment guideline
      from the German Society of Aerospace Medicine-comment.

PMID- 30232735
TI  - Ketamine for Refractory Status Epilepticus: A Systematic Review.
AB  - BACKGROUND: Ketamine is an emerging third-line medication for refractory status
      epilepticus, a medical and neurological emergency requiring prompt and
      appropriate treatment. Owing to its pharmacological properties, ketamine
      represents a practical alternative to conventional anaesthetics. OBJECTIVE: The
      objective of this study was to assess the efficacy and safety of ketamine to
      treat refractory status epilepticus in paediatric and adult populations. METHODS:
      We conducted a literature search using the PubMed database, Cochrane Database of
      Systematic Reviews and ClinicalTrials.gov website. RESULTS: We found no results
      from randomised controlled trials. The literature included 27 case reports
      accounting for 30 individuals and 14 case series, six of which included children.
      Overall, 248 individuals (29 children) with a median age of 43.5 years (range 2
      months to 67 years) were treated in 12 case series whose sample size ranged from
      5 to 67 patients (median 11). Regardless of the status epilepticus type, ketamine
      was twice as effective if administered early, with an efficacy rate as high as
      64% in refractory status epilepticus lasting 3 days and dropping to 32% when the
      mean refractory status epilepticus duration was 26.5 days. Ketamine doses were
      extremely heterogeneous and did not appear to be an independent prognostic
      factor. Endotracheal intubation, a negative prognostic factor for status
      epilepticus, was unnecessary in 12 individuals (10 children), seven of whom were
      treated with oral ketamine for non-convulsive status epilepticus. CONCLUSIONS:
      Although ketamine has proven to be effective in treating refractory status
      epilepticus, available studies are hampered by methodological limitations that
      prevent any firm conclusion. Results from two ongoing studies (ClinicalTrials.gov
      identification number: NCT02431663 and NCT03115489) and further clinical trials
      will hopefully confirm the better efficacy and safety profile of ketamine
      compared with conventional anaesthetics as third-line therapy in refractory
      status epilepticus, both in paediatric and adult populations.

PMID- 30232738
TI  - Metabolic and vascular effects of silybin in hypertensive patients with high 1-h
      post-load plasma glucose.
AB  - Hypertensive patients with normal glucose tolerance (NGT) but 1-h post-load
      plasma glucose >= 155 mg/dl (1-h high), during an oral glucose tolerance test
      (OGTT), show higher insulin resistance and multiple target organ damages.
      Experimental and clinical studies demonstrate that silybin presents anti
      inflammatory and metabolic effects, improving insulin resistance and endothelial
      dysfunction. This study aims to evaluate the effects of the complex silybin
      vitamin E and phospholipids on inflammatory, metabolic and vascular parameters in
      NGT 1-h high hypertensive patients. This is a pilot, single arm, interventional,
      longitudinal study enrolling 50 Caucasian NGT 1-h high hypertensive outpatients,
      27 men and 23 women, age range 42-60 years (mean + SD = 52 +/- 7). After 6 months
      of silybin intake, there is a significant improvement in metabolic profile. The
      glucose response during OGTT significantly improves (AUCglucose0-120 309.6 +/-
      63.4 at baseline vs 254.6 +/- 35.5 at the follow-up, ? = - 55, 95% CI from - 67
      to - 43, p < 0.0001), so as insulin response (AUCinsulin0-120 238.2 +/- 99.1 vs
      159.3 +/- 44.9, ? = - 78.9, 95% CI from - 100.0 to - 57.8, p < 0.0001), in
      accordance with the increase of insulin sensitivity index Matsuda. Silybin intake
      is associated with a significant reduction of both clinical and central systolic
      blood pressure, with betterment in clinical and central pulse pressure and
      reduction of arterial stiffness parameters. In conclusion, this study
      demonstrates that silybin may improve the metabolic aspect and vascular damage in
      NGT 1-h high hypertensive patients who are at higher metabolic and cardiovascular
      risk. Thus, in these patients, silybin might strengthen the effect of
      antihypertensive drugs giving further cardiovascular protection.

PMID- 30232740
TI  - Assessment of Self-Administration of Romiplostim in Patients with Immune
      Thrombocytopenic Purpura after Receipt of Home Administration Training Materials:
      a Cross-Sectional Study.
AB  - INTRODUCTION: Romiplostim is a subcutaneously administered thrombopoietin
      receptor agonist approved in the European Union for self-administration (or
      administration by a caregiver) in selected adult patients with chronic primary
      immune thrombocytopenia refractory to other treatments. To mitigate the risk of
      medication errors due to self-administration, the manufacturer has implemented
      additional risk minimisation measures (RMM) in the form of a Home Administration
      Training (HAT) pack to support the training of both healthcare professionals
      (HCPs) (guide and checklist for patient selection and training) and patients (a
      preparation mat, quick guide booklet, step-by-step guide, self-administration
      diary and DVD/video). OBJECTIVE: The primary objective was to estimate the
      proportion of patients/caregivers who administered romiplostim correctly after
      HAT pack training. METHODS: A multicentre observational study was conducted to
      evaluate the effectiveness of the HAT pack by recording data on a standardised
      collection form during direct observation of patients/caregivers in the act of
      administering romiplostim at the first standard-of-care visit 4 weeks after
      training with the HAT pack. RESULTS: Among the 40 patients/caregivers enrolled
      across 12 study centres in eight European countries, 35 [87.5%; 95% confidence
      interval (CI) 73.9-94.5] administered romiplostim correctly, and five (12.5%; 95%
      CI 5.5-26.1) did not. CONCLUSION: The correct administration of romiplostim by
      most patients/caregivers supports the effectiveness of the HAT pack as an
      additional risk minimisation tool in the population and setting of this study.

PMID- 30232739
TI  - Comment on: "Mixed Approach Retrospective Analyses of Suicide and Suicidal
      Ideation for Brand Compared with Generic Central Nervous System Drugs".

PMID- 30232741
TI  - Nonsteroidal Anti-Inflammatory Drugs and Risk of First Hospitalization for Heart
      Failure in Patients with No History of Heart Failure: A Population-Based Case
      Crossover Study.
AB  - INTRODUCTION: Traditional nonselective, nonsteroidal anti-inflammatory drugs
      (NSAIDs) are known to cause salt and fluid retention and should thus be used
      cautiously in patients with documented heart failure. Recent studies have found
      that some NSAIDs, including cyclooxygenase (COX)-2 inhibitors, are associated
      with an increased risk of incident heart failure regardless of the related
      medical history of the patient. OBJECTIVE: This study aimed to investigate the
      potential link between NSAIDs (both COX-2 inhibitors and traditional nonselective
      NSAIDs) and heart failure in patients without a history of heart failure.
      METHODS: We conducted a case-crossover study using the National Health Insurance
      Research Database (NHIRD) in Taiwan. A total of 5615 subjects with a first
      hospitalization for heart failure between 2005 and 2013 were identified from the
      NHIRD. Exposure to individual NSAIDs between the case period (1-30 days before
      the index date) and control period (121-150 days before the index date) were
      retrieved. Multivariable conditional logistic regression models were used to
      estimate the adjusted odds ratios (aORs) of the incident heart failure associated
      with NSAID use after adjustments for potential confounders. Multiple sensitivity
      analyses, including the case-time-control analysis, were performed to test the
      robustness of the study results. RESULTS: Overall, NSAID use was associated with
      a 1.58-fold risk [aOR 1.58; 95% confidence interval (CI) 1.40-1.79] of heart
      failure leading to hospitalization in the main analysis, and similar results were
      obtained in the case-time-control analysis [aOR 1.40 (95% CI 1.18-1.67)]. The
      increased risks of heart failure were comparable between traditional NSAIDs [aOR
      1.53 (95% CI 1.35-1.74)] and COX-2 inhibitors [aOR 1.74 (95% CI 1.25-2.44)].
      Among all NSAIDs, ketorolac was associated with the highest risk of heart failure
      [aOR 1.98 (95% CI 1.37-2.86)]. CONCLUSION: Both traditional NSAIDs and COX-2
      inhibitors were associated with an increased risk of heart failure leading to
      hospitalization in patients without a related history of heart failure.

PMID- 30232742
TI  - First Conference on Big Data for Pharmacovigilance.

PMID- 30232743
TI  - Authors' Reply to Courtney Suggs and Colleagues' Comment on: "Mixed Approach
      Retrospective Analyses of Suicide and Suicidal Ideation for Brand Compared with
      Generic Central Nervous System Drugs".

PMID- 30232744
TI  - Effects of Probiotic Yogurt on Serum Omentin-1, Adropin, and Nesfatin-1
      Concentrations in Overweight and Obese Participants Under Low-Calorie Diet.
AB  - Data on the effects of probiotics on adipokines such as omentin-1, nesfatin-1,
      and adropin are limited. The aim of this study was to evaluate the effects of
      probiotic yogurt along with a low-calorie diet (LCD) on serum omentin-1, adropin,
      and nesfatin-1 concentrations in obese and overweight individuals. Sixty obese or
      overweight individuals aged 20-50 years old were involved in this randomized
      double-blind placebo-controlled clinical trial. Participants were randomly
      allocated into two groups to consume either probiotic yogurt containing
      Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei
      DN001 (108 CFU/g each) (n = 30) or regular yogurt (n = 30) along with a LCD in
      both groups for 8 weeks. Fasting blood samples were taken at baseline and after
      the 8-week intervention to determine related variables. A significant decrease in
      body fat percentage was observed in the probiotic group compared with the regular
      group after 8 weeks (- 1.51 +/- 069 vs - 0.88 +/- 0.68%, P = 0.002). After the 8
      week intervention, a significant difference in serum adropin concentration (6.04
      +/- 24.46 vs - 8.16 +/- 24.66 pg/ml, P = 0.03 and serum omentin-1 concentration
      (0.09 +/- 1.51 vs - 1.5 +/- 1.8 ng/ml, P = 0.003) was observed between two
      groups. We did not observe any significant changes in nesfatin-1 and other
      anthropometric measures. Overall, probiotic yogurt for 8 weeks among overweight
      or obese individuals along with LCD had beneficial effects on body fat
      percentage, serum omentin-1, and adropin concentration, but it did not have any
      effect on nesfatin-1 level.

PMID- 30232745
TI  - Skimmed Milk-Based Encapsulation for Enhanced Stability and Viability of
      Lactobacillus gastricus BTM 7 Under Simulated Gastrointestinal Conditions.
AB  - The present study investigated skimmed milk and alginate-based encapsulation for
      protection of a probiotic strain, Lactobacillus gastricus BTM7 during storage and
      exposure to simulated gastrointestinal conditions. The investigations have
      revealed that coating with skimmed milk and alginate in a ratio of 1:1 resulted
      in highest encapsulation efficiency of 94% (p < 0.05) with approximately 1 log
      reduction in viable cell count and 90% release of encapsulated cells in 90 min.
      This formulation resulted in 5-fold higher survival of bacteria during storage at
      refrigeration for 21 days (p < 0.05). The encapsulation of L. gastricus BTM7
      provided better protection at the pH of gastric juice or pancreatic conditions
      with 4- and 9-fold increase in survivability after 2 h of incubation. The
      principal component analysis (PCA) revealed the potential of skimmed milk
      supplementation to alginate (1:1) to enhance survival of probiotic strain under
      refrigerated storage, a process that can be safely incorporated into dairy
      products.

PMID- 30232746
TI  - Improved Viability of Microencapsulated Probiotics in a Freeze-Dried Banana
      Powder During Storage and Under Simulated Gastrointestinal Tract.
AB  - Freeze-dried banana powder represents an ideal source of nutrients and has not
      yet been used for probiotic incorporation. In this study, microencapsulation by
      freeze drying of probiotics Lactobacillus acidophilus and Lactobacillus casei was
      made using whey protein isolate (WPI), fructooligosaccharides (FOS), and their
      combination (WPI + FOS) at ratio (1:1). Higher encapsulation yield was found for
      (WPI + FOS) microspheres (98%). Further, microcapsules of (WPI + FOS) were used
      to produce a freeze-dried banana powder which was analyzed for bacterial
      viability under simulated gastrointestinal fluid (SGIF), stability during storage
      at 4  degrees C and 25  degrees C, and chemical and sensory properties. Results
      revealed that (WPI + FOS) microcapsules significantly increased bacteria
      stability in the product over 30 days of storage at 4  degrees C averaging (>=
      8.57 log CFU/g) for L. acidophilus and (>= 7.61 log CFU/g) for L. Casei as
      compared to free cells. Bacteria encapsulated in microspheres (WPI + FOS) were
      not significantly affected by the SGIF, remaining stable up to 7.05 +/- 0.1 log
      CFU/g for L.acidophilus and 5.48 +/- 0.1 log CFU/g for L.casei after 90 min of
      incubation at pH 2 compared to free cells which showed minimal survival. Overall,
      encapsulated probiotics enriched freeze-dried banana powders received good
      sensory scores; they can therefore serve as safe probiotics food carriers.

PMID- 30232747
TI  - Effects of Different Selenium Sources on Laying Performance, Egg Selenium
      Concentration, and Antioxidant Capacity in Laying Hens.
AB  - Supplementation of selenium (Se) is a common practice in the poultry industry via
      sodium selenite (SS) and selenium yeast (SY), while the effects of nano-selenium
      (NS) on laying hens are poorly known. This study aimed to compare the effects of
      NS, SS, and SY on productivity; selenium (Se) deposition in eggs; and antioxidant
      capacity in laying hens. A total of 288 30-week-old Brown Hy-line laying hens
      were randomly assigned into four dietary treatments, which included corn-soybean
      meal basal diet (Con) without Se sources and basal diets supplemented with 0.3 mg
      Se/kg as SS, SY, or NS, respectively. The results exhibited that Se-supplemented
      treatments achieved greater egg production, egg weight, and daily egg mass, also
      better feed conversion ratio than Con group (p < 0.05). Se supplementation
      significant increased egg Se concentration and decreased the egg Se deposition
      efficiency (p < 0.05), while SY or NS supplementation had higher Se deposition
      efficiency than SS group at 35 days (p < 0.05). Moreover, serum glutathione
      peroxidase (GSH-Px) activity increased in SS or NS group compared to Con group (p
      < 0.05). The glutathione peroxidase 4 (GPX-4) mRNA levels in liver were
      significantly higher (p < 0.05) in SS or SY group than in NS group, and mRNA
      levels of the methionine (Met) metabolism gene glycine N-methyltranserfase (GNMT)
      were markedly upregulated (p < 0.05) in SY group compared to SS or NS group.
      Taken together, the results revealed Se from SY is deposited into eggs more
      efficiently than Se from NS or SS, probably via enhancing the route of Met
      metabolism. Meanwhile, it might be concluded that SS or SY supplementation
      directly regulated GSH-Px activity via enhancing GPx4 level, whereas NS via GPx1,
      thus affecting body oxidation and development.

PMID- 30232748
TI  - Dietary Exposure Assessment of Potentially Toxic Trace Elements in Fruits and
      Vegetables Sold in Town of Kapan, Armenia.
AB  - Fruits and vegetables grown under the impact of Armenia's mining industry are
      widely sold in markets of adjacent towns. As the share of fruits and vegetables
      in Armenians' diet is significant, the present study aims to assess the dietary
      exposure of potentially toxic trace elements through the intake of fruits and
      vegetables sold in Kapan town, located in the biggest mining region of Armenia.
      The concentrations of Cu, Mo, Ni, Cr, Pb, Zn, Hg, As, and Cd in 15 types of
      fruits and vegetables were determined. Non-carcinogenic and carcinogenic risks
      were assessed. Although the estimated daily intakes of trace elements for each
      studied food item did not exceed health-based guidelines values, in case of the
      combined consumption of fruits and vegetables estimated cumulative daily intakes
      exceeded reference doses for Cu and Mo. Moreover, carcinogenic risk for the
      majority of fruits and vegetables exceeded the EPA recommended risk level of 10
      6, indicating adverse health effect to local population. The outcomes of this
      study can serve as a basis for further research that will consider many other
      exposure pathways (i.e., inhalation or dermal pathways) in order to ensure the
      safety of the residents living under the impact of mining industry.

PMID- 30232749
TI  - Systems Biology in Aging Research.
AB  - Systems biology is an approach to collect high-dimensional data and analyze in an
      integrated manner. As aging is a complicated physiological functional decline in
      biological system, the methods in systems biology could be utilized in aging
      studies. Here we reviewed recent advances in systems biology in aging research
      and divide them into two major parts. One is the data resource, which includes
      omics data from DNA, RNA, proteins, epigenetic changes, metabolisms, and recently
      single-cell-level variations. The other is the data analysis methods consisting
      of network and modeling approaches. With all the data and the tools to analyze
      them, we could further promote our understanding of the systematic aging.

PMID- 30232750
TI  - Circular RNA in Aging and Age-Related Diseases.
AB  - Circular RNAs (circRNAs) are widely present and participate in a variety of
      biological regulatory activities as a novel type of endogenous noncoding RNA
      molecule. With advances in RNA structure and function analysis, it was found that
      circRNAs are present in a myriad of life processes and longevity in model
      organisms such as mice, flies, and worms. Accumulating evidence indicates the
      involvement of circRNAs in regulation of age-related pathologies such as cancer,
      diabetes, cardiovascular disorders, and neurodegenerative disease, suggesting
      that circRNAs may have great potential implications in clinical and research
      fields. In this chapter, we review recent advances in circRNA functions and
      mechanisms and discuss their roles in aging and age-related diseases. It will
      provide insight into the regulatory roles of circRNAs in aging and age-related
      diseases.

PMID- 30232751
TI  - Noncoding RNAs in Cardiovascular Aging.
AB  - With a progressively growing elderly population, aging-associated cardiovascular
      diseases and other pathologies have brought great burden to the economy, society,
      and individuals. Therefore, identifying therapeutic targets and developing
      effective strategies to prevent from cardiovascular aging are highly needed.
      Accumulating evidences suggest that noncoding RNAs (ncRNAs) such as microRNAs and
      long noncoding RNAs (lncRNAs) play important roles in regulating gene expression,
      which contributes to many pathophysiological processes of cellular senescence,
      aging, and aging-related diseases in cardiovascular systems. Here we provided a
      general overview of ncRNAs as well as the underlying mechanisms involved in
      cardiovascular aging. Although the importance of ncRNAs in cardiovascular aging
      has been reported and commonly acknowledged, further studies are still necessary
      to elucidate the underlying molecular mechanisms.

PMID- 30232752
TI  - Epigenetic Regulation of Vascular Aging and Age-Related Vascular Diseases.
AB  - Vascular aging refers to the structural and functional defects that occur in the
      aorta during the aging process and is characterized by increased vascular cell
      senescence, vascular dyshomeostasis, and vascular remodeling. Vascular aging is a
      major risk factor for vascular diseases. However, the current understanding of
      the biological process of vascular aging and age-related diseases is
      insufficient. Epigenetic regulation can influence gene expression independently
      of the gene sequence and mainly includes DNA methylation, histone modifications,
      and RNA-based gene regulation. Epigenetic regulation plays important roles in
      many physiological and pathophysiological processes and may explain some gaps in
      our knowledge regarding the interaction between genes and diseases. In this
      review, we summarize recent advances in the understanding of the epigenetic
      regulation of vascular aging and age-related diseases in terms of vascular cell
      senescence, vascular dyshomeostasis, and vascular remodeling. Moreover, the
      possibility of targeting epigenetic regulation to delay vascular aging and treat
      age-related vascular diseases is also discussed.

PMID- 30232753
TI  - ApoE and Neurodegenerative Diseases in Aging.
AB  - Age and apolipoprotein E (ApoE) are the mightiest risk factors for dementia and
      cardiovascular diseases, but the underlying mechanisms remain unclear. In human,
      ApoE has three isoforms, ApoE2, ApoE3, and ApoE4, which are expressed by the
      polymorphic alleles: E2, E3, and E4. Among the three polymorphic alleles, apoE
      epsilon4 is the most risk gene. ApoE is the main ligand for the low-density
      lipoprotein (LDL) receptor and the LDL receptor-related protein (LRP),
      functioning as the component of plasma lipoproteins in the transportation of
      lipids. Physiologically, ApoE is a multifunctional protein with central roles in
      lipid metabolism; it transports lipids, including cholesterol, through the
      cerebrospinal fluid (CSF) and plasma. ApoE expression regulation and apoE gene
      polymorphism have an important connection with neurological or neurodegenerative
      diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), ischemic
      stroke, and other diseases.

PMID- 30232755
TI  - Aging of Human Adult Stem Cells.
AB  - With the continuous development of stem cell research in recent years, it is
      realized that stem cell aging may be the core issue of organ aging. As an
      important approach and main content of regenerative medicine, the stem cell
      research brings great hope to overcome difficult diseases and improve the quality
      of life for human beings and become the key to solve this issue. Based on this
      research, the varying characteristics of stem cells in aging could be recognized;
      the role of stem cells in the organ aging and regeneration will be revealed; the
      function of stem cells will be controllable and regulatable in tissues and
      organs; the stem cells from tissues and organs with rapid or slow cell renewal
      (e.g., liver and neuron) could be continuously observed from the levels of
      cellular molecules and dynamic complex. With the assistance of systematical
      research approaches, the function and mechanism studies can be conducted via
      multi-perspectives and levels during the different stages of organ aging and
      regeneration. All of the abovementioned requires great efforts to thoroughly
      understand the basic rule and the way of stem cell regulation in organ aging and
      regeneration. Final to the end, the dream of antiaging, efficient repair, and
      organ remodeling could be realized and also can meet the major needs of
      population health and disease treatment in our country, meaningfully to
      contribute benefits for the health of human beings.

PMID- 30232754
TI  - Brain Aging: Hsp90 and Neurodegenerative Diseases.
AB  - The brain is the most complex organ in the human body and the main component of
      the central nervous system. Because it lacks the ability of regeneration, age is
      a major risk factor for most common neurodegenerative diseases, which caused an
      irreversible cognitive impairment. It has been shown that the function of
      molecular chaperones, majorly heat shock proteins, was compromised and then
      causes the imbalance of protein homeostasis inside the cell, which is the most
      influential reason of brain aging. Here, in this review, we discuss the
      mechanisms underneath the impairment of heat shock protein function during brain
      aging, including transcriptional regulation, posttranslational modification, and
      communication across cells and organs.

PMID- 30232756
TI  - Mechanisms of Hematopoietic Stem Cell Ageing and Targets for Hematopoietic Tumour
      Prevention.
AB  - Hematopoietic stem cells represent a rare population in the bone marrow, with the
      capacity of generating all blood lineage and themselves at the same time. With
      aging, the reconstitution capacity of hematopoietic stem cells decreases
      accompanying with differentiation skewing wherein the myeloid branch dominates in
      both mouse and human. In recent years, various molecular mechanisms that induce
      functional decline of HSC during aging were disclosed including DNA damage
      accumulation, metabolic alteration, defects in protein homeostasis, and aging
      induced changes in the blood circulatory environment. Deciphering the nature of
      HSC aging could improve our knowledge of HSC aging-related diseases and
      furthermore promote the developing of therapeutic interventions for human HSC
      aging and diseases.

PMID- 30232757
TI  - Microbiota and Aging.
AB  - The human gut microbiota is a huge ecosystem that provides lots of functions for
      host development, immune system, and metabolism. Gut microbiota is linked to lots
      of diseases, including human metabolic diseases such as obesity, type 2 diabetes
      (T2D), irritable bowel syndrome, and cardiovascular disease (CVD). Few studies,
      however, have noted the relationship between aging and microbiota; the connection
      between aging and microbiota remains largely to be researched. In this review,
      recent research findings are summarized on the role of gut microbiota in aging
      processes with emphasis on therapeutic potential of microbiome-targeted
      interventions in antiaging medicine.

PMID- 30232758
TI  - Intestinal Homeostasis and Longevity: Drosophila Gut Feeling.
AB  - The association between intestinal homeostasis and life span has caught the
      attention of the research community worldwide. There have been multiple evidences
      which support the role of gut homeostasis in aging. The Drosophila
      gastrointestinal tract is very similar to the mammalian gut, and therefore it can
      directly be used as a model to understand the association between gut microbiota,
      immune system, and aging in humans. In current review we have discussed the
      importance of gut microbiota in aging. Also we have highlighted the importance of
      host immune system and gut aging. Since the increased microbial load in the gut
      activates the host immune system, the dysregulated microbiota can have direct
      implications in gut aging. The proliferation and renewal of intestinal stem cells
      can also affect gut aging. Another important aspect that we have discussed is the
      communication between the gut and the other organ systems which affect the
      overall aging process. Altogether we propose that the Drosophila gut can be a
      good model to improve our understanding of human gut aging.

PMID- 30232759
TI  - Aging Kidney and Aging-Related Disease.
AB  - With the development of society and improvement of health care, the life span is
      much longer than before, which brings serious aging problems. Among all the aging
      problems, renal aging grows to be nonnegligible issue. The aging process of
      kidney is always accompanied with structural and functional changes. Molecular
      changes, including Klotho and Sirtuins, are the basic causes of phenotypical
      changes. Cell senescence and cell autophagy play fundamental roles in the process
      of renal aging. To effectively intervene in the process of renal aging, different
      methods have been tried separately, which could produce different effects.
      Effective intervention of renal aging could be meaningful for healthy state of
      the whole body.

PMID- 30232760
TI  - Aging of the Bone.
AB  - Besides mechanical and protective function, bone serves as a keeper for marrow
      cells and an organ for regulation of calcium ion homeostasis. During aging,
      significant amounts of the bone are lost due to the loss of this delicate balance
      toward increased bone resorption coupled with decreased formation, which leads to
      net bone loss of the aging people. Osteoblasts, osteoclasts, and osteocytes are
      defined by their respective functions of bone formation and bone resorption. So,
      during bone aging, how the bone and bone cells will change are key issues for
      understanding osteoporosis. In this chapter, we focus on the changes of these
      factors during aging of the bone.

PMID- 30232761
TI  - Ovarian Aging and Osteoporosis.
AB  - Osteoporosis is the most common bone metabolic disease with a very high
      morbidity, and women usually got a higher risk of osteoporosis than men. The high
      incidence rate of osteoporosis in women was mainly caused by (1) women having
      fewer skeletons and bone mass, (2) pregnancy consuming a large amount of calcium
      and other nutrients, and most importantly (3) the cease of estrogen secretion by
      ovaries after menopause. Along with ovarian aging, the follicle pool gradually
      declines and the oocyte quality reduced, accompanied with decline in serum
      estrogen. Estrogen deficiency plays an important role in the pathogenesis of
      postmenopausal osteoporosis; it is mainly a result of the recognition that
      estrogen regulates bone remodeling by modulating the production of cytokines and
      growth factors from bone marrow and bone cells. This review will summarize
      current knowledge concerning ovarian aging and postmenopause osteoporosis and
      also discuss clinical treatment and new ideas of drug development for
      osteoporosis.

PMID- 30232762
TI  - Biomarkers of Aging.
AB  - Biomarkers of aging are a biological parameter that can predict the functional
      status of an individual in the absence of disease and can be used to better
      predict morbidity and mortality, compared to using the chronological age alone.
      Most of aging biomarkers were gene, molecules, and protein, which were found in
      basic scientific researches, such as telomeres, proteomics, cytokines, etc.
      However, it is almost impossible for single biomarkers to fully reveal the
      mechanism of aging. Because of the complexity of aging process, the biomarkers of
      aging may need to be composed of multiple genes, proteins, and metabolites. The
      biological age is based on the setting of biological markers, which is a
      parameter for evaluating the functional status of the individual. Aging is not
      only dependent on the process of time. The chronological age is only the
      evaluation indicators of time scale in the aging process. Therefore, biological
      age can be more representative of the true degree of aging than chronological
      age, which provides a quantitative standard for individualized aging. According
      to the factor score, we established biological age score (BAS) = 0.248 (CA) +
      0.195 (IMT) - 0.196 (EDV) - 0.167 (E/A) - 0.166 (MVEL) + 0.188 (PP) + 0.182(FIB)
      + 0.193 (CYSC) through 7 aging biomarkers selected from 108 variables. The study
      found the rate of aging was gradually increased before the age of 75 years old
      and afterward entered a stable plateau. In the future, the new approach may be
      needed to investigate the mechanisms and evaluation of aging.

PMID- 30232763
TI  - Pharmaceutical Intervention of Aging.
AB  - The aging population represents a significant worldwide socioeconomic challenge.
      Aging is an inevitable and multifactorial biological process and primary risk
      factor for most age-related diseases, such as cardiovascular diseases, cancers,
      type 2 diabetes mellitus (T2DM), and neurodegenerative diseases. Pharmacological
      interventions targeting aging appear to be a more effective approach in
      preventing age-related disorders compared with the treatments targeted to
      specific disease. In this chapter, we focus on the latest findings on molecular
      compounds that mimic caloric restriction (CR), supplement nicotinamide adenine
      dinucleotide (NAD+) levels, and eliminate senescent cells, including metformin,
      resveratrol, spermidine, rapamycin, NAD+ boosters, as well as senolytics. All
      these interventions modulate the determinants and pathways responsible for
      aging/longevity, such as the kinase target of rapamycin (TOR), AMP-activated
      protein kinase (AMPK), sirtuins, and insulin-like growth factor (IGF-1) signaling
      (Fig. 15.1).

PMID- 30232764
TI  - Application of Stem Cell Technology in Antiaging and Aging-Related Diseases.
AB  - Stem cells are one kind of cells that have the potential of proliferation and
      differentiation. The human beings are originated from a totipotential stem cell
      fertilized egg. After birth, the proliferation and differentiation of stem cells
      contribute to the development and maturation of individual tissues and organs.
      After maturation, aging is a phases of the life process, the stem cells within
      the individual's tissues ensure the metabolism of different cells and tissues,
      such as the hematopoietic stem cells in the bone marrow, which ensure there are
      still enough red blood cells (RBCs) being responsible for the mission of
      transporting oxygen after a single RBC has completed its 120-day physiological
      life cycle. After pathological damage and necrosis occurring on the intestinal
      epithelial cells or tubular epithelial cells, there will be regenerative
      epithelial cells continuing to maintain the integrity of the structure and
      function of the intestine and renal tubules. The role of stem cells in the
      regeneration and repair of tissues and organs is not only because of the ability
      of proliferation and differentiation of stem cells but also of the secretion
      function of stem cells, which secrete various growth factors and cytokines to
      regulate the tissue microenvironment. For example, mesenchymal stem cells derived
      from bone marrow are important regulators in bone marrow hematopoietic stem cell
      niche. Mesenchymal stem cells maintain the "stemness" of hematopoietic stem cells
      by secreting various cytokines.Aging is a phases of the life process, and all
      creatures obey this rule of nature. Different organs of the body have different
      time of entering into aging. Aging is reflected in structural changes and reduced
      function. Among them, the reduction of regeneration and repair capacity is the
      main feature of aging. As we age, the aging of stem cells in human tissues is a
      major cause of the decline in tissue regeneration capacity. Therefore, the
      elderly's ability of regenerate and repair can be improved by application of
      advance stem cell technology. It can delay the aging process and treat aged
      diseases (showed in Fig. 16.1).

PMID- 30232765
TI  - Which is the Most Reasonable Anti-aging Strategy: Meta-analysis.
AB  - An organism's lifespan is inevitably accompanied by the aging process, which
      involves functional decline, a steady increase of a plethora of chronic diseases,
      and ultimately death. Thus, it has been an ongoing dream of mankind to improve
      health span and extend the lifespan. In the last century, there is a great
      increase in the search for eternal youth and an insatiable appetite for methods
      which could turn back the clock. Survival curves are key components of lifespan
      experiments. Many interventions have been reported to extend the lifespan,
      including the administration of pharmaceuticals, calorie restriction, and genetic
      alteration. However, few studies have attempted to provide a comprehensive
      analysis of the mechanism by which these various methods function to extend
      lifespan. We recently collected survival curves from published papers and
      recovered data by fitting models. The analysis results highlight the overall
      advantage of calorie restriction and its mimetics in aging and demonstrate that
      hypoglycemic agents and antioxidants have a superior effect on lifespan extension
      via a pattern of global integrity compared to other medications. This review
      provides a scientific foundation for the discovery of effective anti-aging agents
      and the formulation of scientific anti-aging strategies.

PMID- 30232766
TI  - Spectrum of lytic lesions of the skull: a pictorial essay.
AB  - Lytic lesions of the skull include a wide range of diseases, ranging from benign
      conditions such as arachnoid granulations or vascular lacunae, to aggressive
      malignant lesions such as lymphomas or metastases. An early and correct
      characterisation of the nature of the lesion is, therefore, crucial, in order to
      achieve a fast and appropriate treatment option. In this review, we present the
      radiological appearance of the most frequent lytic lesions of the skull,
      describing findings from different imaging modalities (plain X-rays, CT and MRI),
      with particular attention to diagnostic clues and differential diagnoses.
      TEACHING POINTS: * Osteolytic skull lesions may be challenging to diagnose. *
      Association of different imaging techniques may aid image interpretation. *
      Clinical information and extensive knowledge of possible differential diagnoses
      is essential. * Some osteolytic tumours, although benign, may present as locally
      aggressive lesions. * Malignant lesions require accurate staging, followed by
      variable treatment approaches.

PMID- 30232767
TI  - Radiological review of skull lesions.
AB  - Calvarial lesions are often asymptomatic and are usually discovered incidentally
      during computed tomography or magnetic resonance imaging of the brain. Calvarial
      lesions can be benign or malignant. Although the majority of skull lesions are
      benign, it is important to be familiar with their imaging characteristics and to
      recognise those with malignant features where more aggressive management is
      needed. Clinical information such as the age of the patient, as well as the
      patient's history is fundamental in making the correct diagnosis. In this
      article, we will review the imaging features of both common and uncommon
      calvarial lesions, as well as mimics of these lesions found in clinical practice.
      TEACHING POINTS: * Skull lesions are usually discovered incidentally; they can be
      benign or malignant. * Metastases are the most frequent cause of skull lesions. *
      Metastatic lesions are most commonly due to breast cancer in adults and
      neuroblastoma in children. * Multiple myeloma presents as the classic "punched
      out" lytic lesions on radiographs. * Eosinophilic granuloma is an osteolytic
      lesion with bevelled edges.

PMID- 30232769
TI  - Autosomal-recessive iron deficiency anemia, dystonia and hypermanganesemia caused
      by new variant mutation of the manganese transporter gene SLC39A14.
AB  - This inborn error of manganese metabolism has only recently been identified. A
      total of 28 affected individuals from ten families are known worldwide. Mutations
      in SLC39A14, encoding a Mn uptake transporter, have recently been recognized to
      cause excessive Mn concentrations in the blood which is believed to be neurotoxic
      and lead to a parkinsonian-like movement disorder caused by accumulation of Mn in
      the basal ganglia. We are reporting a new variant of SLC39A14 gene mutation (OMIM
      608736 8p21.3) that has never been described in the literature so far. The index
      case is a 3-year-old female who was born at 30 weeks' gestation by emergency
      lower segment caesarean section, the second of twins, weighing 1.4 kg. Parents
      have a consanguineous marriage (first cousins) and have four healthy male
      children. She presented at 30 months of age with history of unsteady gait of 4
      months duration and is progressively worsening. She became stiff and has lost all
      of her locomotor skills. Apart from low serum iron and iron deficiency anemia,
      her initial work up was unremarkable. T1-weighted MRI brain showed bilateral
      hyperintense signal in basal ganglia, mid-brain and pontine tegmentum giving rise
      to the characteristic eye-of-the-tiger sign. Genetic DNA evaluation (Whole Exome
      Sequencing WES) identified the homozygous missense variant c.1136.T in exon 7 of
      SLC39A14 gene which is associated with hypermanganesemia. Whole blood Mn was
      markedly raised at 150 nmol/L (8 mg/L) (normal 10 nmol/L, 0.7 mg/Bioscientia).
      This young girl has just started treatment with intravenous disodium calcium
      edetate and oral iron.

PMID- 30232768
TI  - Executive Summary of the 2018 Joint Consensus Document on Cardiovascular Disease
      Prevention in Italy.
AB  - Cardiovascular diseases (CVDs) are the leading cause of death, disability and
      hospitalization in Italy. Primary prevention strategies are able to prevent
      clinically evident CVDs, mostly by early identifying asymptomatic, otherwise
      healthy individuals at risk of developing CVDs. A more modern approach
      recommended for effective CVD prevention is based on "4P", that is: Predictive,
      Preventive, Personalized and Participative. This executive document reflects the
      key points of a consensus paper on CV prevention in Italy, realized though the
      contribution of different Italian Scientific Societies and the National Research
      Council, and coordinated by the Italian Society of Cardiovascular Prevention
      (SIPREC), published in 2018. The need for such document relies on the difficulty
      to apply "sic et simpliciter" European guidelines, to which this document is
      largely inspired, to national, regional and local realities, in this
      Mediterranean country, namely Italy. Indeed, our Country has specific features in
      terms of demography, socio-cultural habits, distribution and prevalence of risk
      factors, organization, policy and access to National Health Service compared to
      other European countries.

PMID- 30232772
TI  - ECOTOX, new questions for terrestrial and aquatic ecotoxicology.

PMID- 30232770
TI  - Quantitative mechanisms of cadmium adsorption on rice straw- and swine manure
      derived biochars.
AB  - We quantified and investigated mechanisms for Cd2+ adsorption on biochars
      produced from plant residual and animal waste at various temperatures. Ten
      biochars were produced by pyrolysis of rice straw (RB) and swine manure (SB) at
      300-700  degrees C and characterized. The Cd2+ adsorption isotherms, adsorption
      kinetics, and desorption characteristics were studied via a series of batch
      experiments, and Cd2+-loaded biochars were analyzed by SEM-EDS and XRD. The total
      Cd2+ adsorption capacity (Qc) increased with pyrolysis temperature for both
      biochars, however, rice straw-derived biochars had greater Qc than swine manure
      derived biochars; hence, the biochar derived from rice straw at 700  degrees C
      (RB700) had the largest Qc, 64.4 mg g-1, of all studied biochars. Cadmium
      adsorption mechanisms in this study involved precipitation with minerals (Qcp),
      cation exchange (Qci), complexation with surface functional groups (Qco), and Cd
      pi interactions (Qcpi). Both the pyrolysis temperature and feedstock affected the
      quantitative contributions of the various adsorption mechanisms. The relative
      percent contributions to Qc for Cd2+ adsorption by RB and SB were 32.9-72.9% and
      35.0-72.5% for Qcp, 21.7-50.9% and 20.4-43.3% for Qci, 2.2-14.8% and 1.4-18.8%
      for Qco, and 1.4-3.1% and 3.0-5.8% for Qcpi, respectively. For biochars produced
      at higher pyrolysis temperatures, the contributions of Qcp and Qcpi to adsorption
      increased, while the contributions of Qci and Qco decreased. Generally, Qcp
      dominated Cd2+ adsorption by high-temperature biochars (700  degrees C)
      (accounting for approximately 73% of Qc), and Qci was the most prominent
      mechanism for low-temperature biochars (400  degrees C) (accounting for 43.3
      50.9% of Qc). Results suggested that biochar derived from rice straw is a
      promising adsorbent for the Cd2+ removal from wastewater and that the low
      temperature biochars may outperform the high-temperature biochars for Cd2+
      immobilization in acidic water or soils.

PMID- 30232773
TI  - Speciation and uptake of antimony and arsenic by two populations of Pteris
      vittata L. and Holcus lanatus L. from co-contaminated soil.
AB  - This study aimed to investigate the Sb and As co-accumulating processes of Pteris
      vittata under soil culture condition, including the transformation of Sb and As,
      and the difference in co-accumulating ability among different plant
      species/populations. Two populations of P. vittata and one population of As
      tolerant species Holcus lanatus L. were grown on soil co-contaminated by Sb and
      As. Sb and As speciation in plants was assessed by X-ray absorption near-edge
      structure (XANES) spectroscopy. P. vittata displayed strong As- but limited Sb
      accumulating ability, with the highest shoot concentrations of As and Sb reaching
      455 and 26 mg kg-1, respectively. After 28 days culture, the concentrations of Sb
      and As in the soil solution were reduced by up to 22% and 36% in the P. vittata
      treatments, respectively. Holcus lanatus showed limited uptake for both
      metalloids. In P. vittata, the reduction of arsenate to arsenite occurred (with
      As in shoots all existing as arsenite), but limited reduction of antimonate to
      antimonite (with more than 90% of Sb in shoots existing as antimonate) was
      observed. In terms of the differences in metalloid uptake between the two P.
      vittata populations, the population from the habitat with higher soil As
      concentration showed 35% higher As uptake than the population from the habitat
      with lower As concentration. This populational difference may partly result from
      varying As transformation efficiencies. However, no significant difference was
      observed in Sb accumulation between the two populations.

PMID- 30232771
TI  - Screening of candidate gene responses to cadmium stress by RNA sequencing in
      oilseed rape (Brassica napus L.).
AB  - Cadmium (Cd) stress is one of the most serious threats to agriculture in the
      world. Oilseed rape (Brassica napus L.) is an important oil crop; however, Cd can
      easily accumulate in rapeseed and thus harm human health through the food chain.
      In the first experiment, our purpose was to measure the Cd accumulation in mature
      B. napus plants and its influences on fatty acid composition. The results showed
      that most Cd was accumulated in the root, and the seed fatty acid content was
      considerably different at different Cd toxicity levels. In the second experiment,
      7-day-old B. napus seedlings stressed by Cd (1 mM) for 0 h (CK-0h), 24 h (T-24h),
      or 72 h (T-72h) were submitted to physiological and biological analyses, RNA-Seq
      and qRT-PCR. In total, 5469 and 6769 differentially expressed genes (DEGs) were
      identified in the comparisons of "CK-0h vs T-24h" and "CK-0h vs T-72h",
      respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathway analyses showed that the photosynthetic and glutathione (GSH)
      pathways were significantly enriched in response to Cd stress. Key factors in the
      response to Cd stress included BnPCS1, BnGSTU12, BnGSTU5, and BnHMAs. The
      transcription factors BnWRKY11 (BnaA03g51590D), BnWRKY28 (BnaA03g43640D),
      BnWRKY33 (BnaA03g17820D), and BnWRKY75 (BnaA03g04160D) were upregulated after Cd
      exposure. The present study revealed that upregulation of the genes encoding GST
      and PCS under Cd stress promoted the formation of low-molecular weight complexes
      (PC-Cd), and upregulation of heavy metal ATPase genes induced PC-Cd transfer to
      vacuoles. These findings may provide the basis for the molecular mechanism of the
      response of B. napus to Cd.

PMID- 30232774
TI  - Production of gasoline range hydrocarbons from catalytic cracking of linoleic
      acid over various acidic zeolite catalysts.
AB  - Employment of edible oils as alternative green fuel for vehicles had raised
      debates on the sustainability of food supply especially in the third-world
      countries. The non-edible oil obtained from the abundantly available rubber seeds
      could mitigate this issue and at the same time reduce the environmental impact.
      Therefore, this paper investigates the catalytic cracking reaction of a model
      compound named linoleic acid that is enormously present in the rubber seed oil.
      Batch-scale experiments were conducted using 8.8 mL Inconel batch reactor having
      a cyclic horizontal swing span of 2 cm with a frequency of 60 cycles per minute
      at 450  degrees C under atmospheric condition for 90 min. The performance of HZSM
      5, HBeta, HFerrierite, HMordenite and HY catalysts was tested for their
      efficiency in favouring gasoline range hydrocarbons. The compounds present in the
      organic liquid product were then analysed using GC-MS and classified based on
      PIONA which stands for paraffin, isoparaffin, olefin, naphthenes and aromatics
      respectively. The results obtained show that HZSM-5 catalyst favoured gasoline
      range hydrocarbons that were rich in aromatics compounds and promoted the
      production of desired isoparaffin. It also gave a higher cracking activity;
      however, large gaseous as by-products were produced at the same time.

PMID- 30232775
TI  - Remediation of TCE-contaminated groundwater using KMnO4 oxidation: laboratory and
      field-scale studies.
AB  - The objectives of this study were to (1) conduct laboratory bench and column
      experiments to determine the oxidation kinetics and optimal operational
      parameters for trichloroethene (TCE)-contaminated groundwater remediation using
      potassium permanganate (KMnO4) as oxidant and (2) to conduct a pilot-scale study
      to assess the efficiency of TCE remediation by KMnO4 oxidation. The controlling
      factors in laboratory studies included soil oxidant demand (SOD), molar ratios of
      KMnO4 to TCE, KMnO4 decay rate, and molar ratios of Na2HPO4 to KMnO4 for
      manganese dioxide (MnO2) production control. Results show that a significant
      amount of KMnO4 was depleted when it was added in a soil/water system due to the
      existence of natural soil organic matters. The presence of natural organic
      material in soils can exert a significant oxidant demand thereby reducing the
      amount of KMnO4 available for the destruction of TCE as well as the overall
      oxidation rate of TCE. Supplement of higher concentrations of KMnO4 is required
      in the soil systems with high SOD values. Higher KMnO4 application resulted in
      more significant H+ and subsequent pH drop. The addition of Na2HPO4 could
      minimize the amount of produced MnO2 particles and prevent the clogging of soil
      pores, and TCE oxidation efficiency would not be affected by Na2HPO4. To obtain a
      complete TCE removal, the amount of KMnO4 used to oxidize TCE needs to be higher
      than the theoretical molar ratio of KMnO4 to TCE based on the stoichiometry
      equation. Relatively lower oxidation rates are obtained with lower initial TCE
      concentrations. The half-life of TCE decreased with increased KMnO4
      concentrations. Results from the pilot-scale study indicate that a significant
      KMnO4 decay occurs after the injection due to the reaction of KMnO4 with soil
      organic matters, and thus, the amount of KMnO4, which could be transported from
      the injection point to the downgradient area, would be low. The effective
      influence zone of the KMnO4 oxidation was limited to the KMnO4 injection area
      (within a 3-m radius zone). Migration of KMnO4 to farther downgradient area was
      limited due to the reaction of KMnO4 to natural organic matters. To retain a
      higher TCE removal efficiency, continuous supplement of high concentrations of
      KMnO4 is required. The findings would be useful in designing an in situ field
      scale ISCO system for TCE-contaminated groundwater remediation using KMnO4 as the
      oxidant.

PMID- 30232776
TI  - Influence of sex on biomarkers of oxidative stress in the kidney, lungs, and
      liver of rabbits after exposure to diazinon.
AB  - The present study evaluated the effect of two oral doses of the pesticide
      diazinon (25 and 125 mg/kg bw) on four biochemical parameters (malondialdehyde
      and glutathione levels, and catalase and glutathione S-transferase enzymatic
      activities) in the kidney, lungs, and liver of rabbit after 10 days of exposure.
      Malondialdehyde levels were significantly greater in exposed animals compared to
      controls, especially in the animals exposed to the higher dose of the pesticide.
      This result was reflected in the glutathione levels, which were significantly
      lower at that same higher dose. Catalase activity was also inhibited by the
      higher dose of the pesticide in all three organs analysed, whereas inhibition of
      glutathione S-transferase activity was only significant for the kidney and lungs.
      There were some slight differences between the sexes: taking the results for all
      three organs, the higher dose of diazinon resulted in a clearly significant
      inhibitory effect on the catalase activity and glutathione levels in males, and a
      significant enhancing effect on the malondialdehyde levels in females. These
      results help to confirm the interest of considering such endogenous factors in
      future ecotoxicological studies, and that the four biomarkers considered are
      suitable for reflecting the toxic effects of diazinon on rabbits, especially the
      effects related to oxidative stress. Graphical abstract.

PMID- 30232777
TI  - Diltiazem Promotes Regenerative Axon Growth.
AB  - Axotomy results in permanent loss of function after brain and spinal cord
      injuries due to the minimal regenerative propensity of the adult central nervous
      system (CNS). To identify pharmacological enhancers of axon regeneration, 960
      compounds were screened for cortical neuron axonal regrowth using an in vitro
      cortical scrape assay. Diltiazem, verapamil, and bromopride were discovered to
      facilitate axon regeneration in rat cortical cultures, in the presence of
      chondroitin sulfate proteoglycans (CSPGs). Diltiazem, an L-type calcium channel
      blocker (L-CCB), also promotes axon outgrowth in adult primary mouse dorsal root
      ganglion (DRG) and induced human sensory (iSensory) neurons.

PMID- 30232779
TI  - The role of DENND1A and CYP19A1 gene variants in individual susceptibility to
      obesity in Turkish population-a preliminary study.
AB  - Single nucleotide polymorphisms (SNPs), the most common genetic variations in
      human genome, can manage the predisposition of certain complex diseases or
      situations such as obesity. Genetic polymorphisms also play an important role as
      they can impact a population's susceptibility to being overweight or obese and
      developing related chronic complications such as hypertension, coronary heart
      disease, diabetes and cancer. The present study comprised of 193 unrelated
      healthy volunteers (120 females and 73 males) with Turkish origin. Only female
      adolescents (n = 110) were divided into 2 categories according to their BMI
      values as overweight (BMI >= 25) and normal (18.5 < BMI < 25) according to WHO
      classification. Genomic DNA was isolated from venous blood samples and genotyping
      of DENND1A rs10818854 and CYP19A1 rs2414096 variants was performed on Roche Light
      Cycler 2.0 Real-Time PCR platform. Serum hormone levels were analyzed by
      Electrochemiluminescent Immunoassay (ECLIA; Roche diagnostics). The genotype
      distributions were consistent with the Hardy-Weinberg equilibrium for both SNPs
      in the studied population (p > 0.05). The genotype distribution of DENND1A
      rs10818854 was determined for the first time in Turkish population and the
      variant allele frequency was found as 0.095. According to reduced sex hormone
      binding globulin levels and increased free androgen index in the present study,
      obesity was linked with hyperandrogenism in female subjects. Both polymorphisms
      were investigated as potential genetic susceptibility markers for obesity and
      neither DENND1A nor CYP19A1 showed any associations.

PMID- 30232778
TI  - Cigarette Smoking and All-Cause and Cause-Specific Adult Mortality in the United
      States.
AB  - This study illuminates the association between cigarette smoking and adult
      mortality in the contemporary United States. Recent studies have estimated
      smoking-attributable mortality using indirect approaches or with sample data that
      are not nationally representative and that lack key confounders. We use the 1990
      2011 National Health Interview Survey Linked Mortality Files to estimate relative
      risks of all-cause and cause-specific mortality for current and former smokers
      compared with never smokers. We examine causes of death established as
      attributable to smoking as well as additional causes that appear to be linked to
      smoking but have not yet been declared by the U.S. Surgeon General to be caused
      by smoking. Mortality risk is substantially elevated among smokers for
      established causes and moderately elevated for additional causes. We also
      decompose the mortality disadvantage among smokers by cause of death and estimate
      the number of smoking-attributable deaths for the U.S. adult population ages 35+,
      net of sociodemographic and behavioral confounders. The elevated risks translate
      to 481,887 excess deaths per year among current and former smokers compared with
      never smokers, 14 % to 15 % of which are due to the additional causes. The
      additional causes of death contribute to the health burden of smoking and should
      be considered in future studies of smoking-attributable mortality. This study
      demonstrates that smoking-attributable mortality must remain a top population
      health priority in the United States and makes several contributions to further
      underscore the human costs of this tragedy that has ravaged American society for
      more than a century.

PMID- 30232780
TI  - Isolation and characterization of microsatellite markers for conservation
      management of the endangered Great-billed Seed-finch, Sporophila maximiliani
      (Aves, Passeriformes), and cross-amplification in other congeners.
AB  - The Great-billed Seed-finch, Sporophila maximiliani, is a threatened neotropical
      bird that has declined mainly due to illegal trapping, with very few records in
      the wild in the last two decades. Despite the existence of a considerable captive
      population that could be used for reintroductions into the wild, many individuals
      are known to be hybrids either with other species or subspecies of the genus.
      Forensic investigations are urgently needed to distinguish between birds born in
      captivity from those from illegal trade. Microsatellites can be useful tools to
      assess individual admixture levels and to perform parentage tests that may
      confirm the origin of animals, but only a few loci are available for this group
      of birds. Here, we provide a set of 14 microsatellite loci isolated from the S.
      maximiliani, many of which also amplified and were polymorphic in the Pearly
      bellied Seedeater, S. pileata, and in the Copper Seedeater, S. bouvreuil. In ten
      loci selected for the S. maximiliani, the number of alleles per locus varied from
      four to nine and observed and expected heterozygosities ranged from 0.13 to 1 and
      0.56 to 0.83, respectively. These loci proved to be highly informative for
      forensic analyses, indicating that they may be useful for conservation management
      plans in these endangered tropical birds.

PMID- 30232782
TI  - Correction to: Plant stem cells: what we know and what is anticipated.
AB  - This correction stands to correct Fig. 2 of the original article as Fig. 2
      provided in the manuscript has been modified. The corrected figure has been
      provided herewith. The original article has been corrected.

PMID- 30232781
TI  - Description of rare mutations and a novel variant in Brazilian patients with
      Cystic Fibrosis: a case series from a referral center in the Bahia State.
AB  - Knowledge of the genetic profile of Cystic Fibrosis (CF) contributes to a better
      understanding of the genotype/phenotype relationship, particularly in mixed
      populations such as in Brazil. To describe clinical data of CF patients with rare
      or not yet observed CFTR gene mutations in Brazil. It was a case series of CF
      patients followed-up at a referral center. Clinical and laboratory data were
      obtained through medical records. Molecular analysis of the mutations was
      performed by conventional methods and/or by next-generation sequencing. Ten
      patients were studied, seven had five pathogenic mutations without previous
      description in Brazil (Q1100P, Y109C, A107P, E1409K and K162E), one of which has
      not yet been reported in patients with CF (A107P). Among the seven patients,
      three (two siblings) had the second mutant allele of rare occurrence among
      Brazilians patients (G1069R and 2307insA). Three other patients also had at least
      one rare variant (V201M, S466X and G1069R). The age of the CF diagnosis ranged
      from 1 to 190 months in the ten cases and the main clinical manifestations were
      respiratory symptoms and difficulty in gaining weight. All but one patient
      presented clinical and/or laboratory data compatible with pancreatic
      insufficiency. The identification of rare or not yet described CFTR mutations in
      patients with CF in Brazil highlights the high genetic heterogeneity in this
      population. Knowledge of the genotypic profile of Brazilian CF patients can
      contribute to the development of specific mutation panels for the genetic
      investigation targeting each region of the country, as well as helping to
      understand the complex genotype/phenotype relationship, especially in mixed
      populations.

PMID- 30232784
TI  - Deregulated iron metabolism in bone marrow from adenine-induced mouse model of
      chronic kidney disease.
AB  - Although the primary cause of anemia in chronic kidney disease (CKD) is lack of
      sufficient erythropoietin (EPO), other factors may be involved, including the
      deregulation of iron metabolism. To clarify the mechanism of deranged
      erythropoiesis in CKD, we evaluated bone marrow (BM) cells in adenine-induced CKD
      mice. They showed even higher EPO expression in the kidney. Hepatic hepcidin mRNA
      and plasma hepcidin and ferritin levels were increased. Flow cytometry revealed a
      decrease in the number of cells expressing transferrin receptor (TfR), or late
      erythroid progenitors in BM; these cells correspond to proerythroblasts, and
      basophilic and polychromatic erythroblasts. In CKD mice, levels of erythroferrone
      mRNA in BM and splenic cells were significantly decreased, and MafB protein
      levels in BM cells were significantly increased. These results suggest that, in
      BM, the decrease in TfR, which may be associated with increased MafB levels, and
      the decrease in erythroferrone increase hepatic hepcidin expression, which may
      perturb iron recycling and erythropoiesis.

PMID- 30232783
TI  - Prospective validation of the EuroSCORE II risk model in a single Dutch cardiac
      surgery centre.
AB  - OBJECTIVE: The EuroSCORE I was one of the most frequently used pre-operative risk
      models in cardiac surgery. In 2011 it was replaced by its successor the EuroSCORE
      II. This study aims to validate the EuroSCORE II and to compare its performance
      with the EuroSCORE I in a Dutch hospital. METHODS: The EuroSCORE II was
      prospectively validated in 2,296 consecutive cardiac surgery patients between 1
      April 2012 and 1 January 2014. Receiver operating characteristic curves on in
      hospital mortality were plotted for EuroSCORE I and EuroSCORE II, and the area
      under the curve was calculated to assess discriminative power. Calibration was
      assessed by comparing observed versus expected mortality. Additionally, analyses
      were performed in which we stratified for type of surgery and for elective versus
      emergency surgery. RESULTS: The observed mortality was 2.4% (55 patients). The
      discriminative power of the EuroSCORE II surpassed that of the EuroSCORE I (area
      under the curve EuroSCORE II 0.871, 95% confidence interval (CI) 0.832-0.911;
      area under the curve additive EuroSCORE I 0.840, CI 0.798-0.882; area under the
      curve logistic EuroSCORE I 0.761, CI 0.695-0.828). Both the additive and the
      logistic EuroSCORE I overestimated mortality (predictive mortality additive
      EuroSCORE I median 5.0%, inter-quartile range 3.0-8.0%; logistic EuroSCORE I
      10.7%, inter-quartile range 5.8-13.9), while the EuroSCORE II underestimated
      mortality (median 1.6%, inter-quartile range 1.0-3.5). In most stratified
      analyses the EuroSCORE II performed better. CONCLUSION: Our results show that the
      EuroSCORE II produces a valid risk prediction and outperforms the EuroSCORE I in
      elective cardiac surgery patients.

PMID- 30232785
TI  - Introduction to "Experimental Approaches to the Study of Child Language: A Cross
      Linguistic Perspective".

PMID- 30232786
TI  - Meeting Residents Halfway: the Geriatric Psychiatry Residency Track.

PMID- 30232787
TI  - Diagnosis and Management of Acute Encephalitis in Children.
AB  - Acute encephalitis is a common cause of death and neurodevelopmental problems in
      children. The causative agents are numerous including infectious agents such as
      viruses, bacteria, mycobacteria and protozoa; para-infectious and immune mediated
      disorders such as acute disseminated encephalomyelitis (ADEM) and autoimmune
      encephalitis, especially the recently described anti-NMDA receptor encephalitis.
      Also, many viral associated encephalopathies such as acute necrotizing
      encephalopathy can mimic the presentation of acute encephalitis. In this article,
      authors describe the approach to the diagnosis and management of acute
      encephalitis in children.

PMID- 30232788
TI  - Factors Associated with Readmission of Pediatric Patients in a Developing Nation.
AB  - OBJECTIVES: To determine the incidence of readmission in pediatric patients in a
      tertiary care hospital in a developing nation and to ascertain factors
      precipitating readmissions. METHODS: A prospective study was conducted from
      February 2016 through January 2017 at a tertiary care hospital. Children between
      1 mo to 15 y of age were included if they were readmitted within 60 d of
      discharge. The risk factors for readmission were determined on the basis of
      medical record review and a structured questionnaire and the ascribed cause of
      readmission was grouped into three categories: Patient specific factors, Hospital
      specific factors and Unrelated/ New illness. RESULTS: The readmission rate was
      3%, out of which 80.66% were found to be causally related to the index admission.
      Several sociodemographic characteristics i.e. lack of health information like
      television, lower socioeconomic status, absence of adequate breastfeeding, lower
      age, migrants were found to be significantly associated with readmission along
      with other patient specific factors like presence of cardiac disease, presence of
      comorbid conditions like anemia, malnutrition, and global developmental delay.
      The most important cause for readmission was determined as patient specific
      (48.66%) followed by hospital specific (38%) and unknown/unrelated factors
      (13.33%). CONCLUSIONS: The progression of the primary illness and social
      determinants of pediatric readmissions are important contributing risk factors
      for readmission in developing countries in pediatric patients. Multicentric
      studies are needed from this region of the world to include different hospital
      readmissions rate and to address the issue of potential preventability of
      pediatric readmissions.

PMID- 30232789
TI  - Corticotrophin-ACTH in Comparison to Prednisolone in West Syndrome - A Randomized
      Study.
AB  - OBJECTIVE: To compare the outcomes of adrenocorticotrophic hormone (ACTH) and
      Prednisolone therapy in children with West syndrome. METHODS: The study was done
      at a tertiary health centre for children. The pediatric neurologist at the centre
      enrolled children into the study based on the inclusion and exclusion criteria.
      They were evaluated in detail, classified according to etiologic type and then,
      randomly assigned into two treatment groups, either ACTH or Prednisolone. They
      were followed at regular intervals till 6 mo. RESULTS: There was no difference
      between ACTH and Prednisolone groups with respect to all the outcomes measured.
      Cessation of spasms was achieved in 6/15 (40%) in Prednisolone group and 9/18
      (50%) in ACTH group (p = 0.3906). The average time for achieving cessation was
      6.9 and 8 d in ACTH and Prednisolone groups respectively (p = 0.7902). The
      relapse rates were 18.18 and 50% in ACTH and Prednisolone groups respectively (p
      = 0.28). The side-effects profile, subsequent epilepsy rates and improvement in
      milestones were similar in both the treatment groups. CONCLUSIONS: There is no
      significant difference in children treated with ACTH and Prednisolone. Study
      results cannot be generalized due to small sample size. However, Prednisolone can
      be a suitable alternative to ACTH in resource poor settings.

PMID- 30232791
TI  - Gender and Racial/Ethnic Differences in the Association Between Alcohol Drinking
      Patterns and Body Mass Index-the National Health and Nutrition Examination
      Survey, 1999-2010.
AB  - BACKGROUND: Racial/ethnic variations in both alcohol consumption and obesity
      prevalence are well established. However, previous research indicates that
      drinking patterns influence the relation of alcohol intake to body mass index
      (BMI), and information on racial/ethnic differences in the relation of drinking
      pattern to BMI is lacking. METHODS: Multi-year cross-sectional data extracted
      from the 1999-2010 National Health and Nutrition Examination Survey for adults >=
      20 years (N = 25,816) were used. Effects of drinking patterns were analyzed using
      a linear dose-response model that considered the joint effects of frequency
      (number of days in the past year that at least one drink was consumed) and dosage
      (the number of drinks consumed in excess of the first drink on days when more
      than one drink was consumed). RESULTS: For all racial/ethnic groups except
      Mexican Americans, current drinkers had a lower mean BMI than non-drinkers. Mean
      BMI differences were - 0.721 kg/m2 for non-Hispanic white (white) men and - 1.292
      kg/m2 for white women. Among drinkers, drinking frequency was negatively
      associated with BMI for all racial/ethnic groups; however, this effect was
      significantly smaller for Mexican American men and other Hispanic men than white
      men. Dosage was positively associated with BMI among all racial/ethnic groups
      except Mexican American women and other Hispanic women; this effect was
      significantly stronger among black women than white women. CONCLUSION: Gender and
      racial/ethnic differences in the relation of drinking patterns to BMI should be
      taken into consideration when investigating factors that influence the effect of
      alcohol consumption on BMI.

PMID- 30232790
TI  - Sex-Specific Changes in Physical Performance Following Military Training: A
      Systematic Review.
AB  - INTRODUCTION: Men and women joining the military undergo the same training, often
      in mixed-sex platoons. Given the inherent physiological and physical performance
      differences between men and women, it is reasonable to question whether sex
      differences exist in the adaptation to military training and, therefore, whether
      sex-specific training should be employed to optimise training adaptations.
      OBJECTIVE: To systematically review the literature evaluating changes in the
      physical performance of men and women following military training. METHODS: Six
      database sources were searched in addition to extensive secondary searching.
      Primary prospective intervention studies (all designs) evaluating physical
      training interventions in military populations, reporting pre- to post-training
      changes in physical fitness outcomes for both women and men, were included.
      RESULTS: We screened 3966 unique records. Twenty-nine studies (n = 37 study
      reports) were included, most of which were conducted in the USA and evaluated
      initial training for military recruits. Positive changes were more consistently
      observed in aerobic fitness and muscle strength (whole body and upper body)
      outcomes than lower body strength, muscle power or muscle endurance outcomes,
      following physical training. Relative pre- to post-training changes for all
      outcome measures tended to be greater in women than men although few
      statistically significant sex by outcome/time interactions were observed.
      CONCLUSION: Improvements in some, but not all, performance components were
      observed following a period of military training. Largely, these improvements
      were not significantly different between sexes. Further prospective research is
      needed to evaluate sex-specific differences in the response to physical training
      in controlled conditions to improve military physical training outcomes for both
      sexes.

PMID- 30232792
TI  - Examining the Social Patterning of Postpartum Depression by Immigration Status in
      Canada: an Exploratory Review of the Literature.
AB  - Postpartum depression (PPD) refers to a woman's experience with any depressive
      episode occurring within the first year of the postpartum period (Stewart et al.,
      2008;53(2):121-4). While PPD is a global phenomenon, the distribution of PPD
      within populations is not universal. Indeed, evidence from the Canadian
      literature confirms a significant disparity in PPD outcomes, as the prevalence
      rate of PPD is markedly increased among immigrant women (Stewart et al.,
      2008;53(2):121-4), and immigration status emerges as an important risk factor for
      PPD. However, these two findings alone do not explain the reasons why this
      particular social patterning emerges. This review essay synthesizes findings on
      the prevalence and risk of PPD among immigrant women in Canada. It then draws on
      recent literature to propose three key mechanisms underlying why this social
      patterning emerges, namely (1) social support, (2) socioeconomic status, and (3)
      life stressors. These mechanisms are analyzed through the World Health
      Organization's conceptual framework of the social determinants of health (WHO,
      2010; Statistics Canada, 2017). Additionally, this review essay seeks to assess
      the current state of intervention strategies piloted in Canada for PPD prevention
      and highlight gaps in the literature on intervention strategies for immigrant
      women specifically.

PMID- 30232793
TI  - What Happened to Disparities in CRC Screening Among FFS Medicare Enrollees
      Following Medicare Modernization?
AB  - The Medicare Modernization Act of 2003, implemented in 2006, increased managed
      care options for seniors. It introduced insurance plans for prescription drug
      coverage for all Medicare beneficiaries, whether they were enrolled in FFS or
      managed care (Medicare Advantage) plans. The availability of drug coverage
      beginning in 2006 served to free up budgets for FFS Medicare enrollees that could
      be used to make copayments for colorectal cancer (CRC) screening using endoscopy
      (colonoscopy or sigmoidoscopy). In 2007, Medicare eliminated the copayments
      required by seniors for CRC screening by endoscopy. Later in 2008, CRC screening
      by colonoscopy became part of the gold standard for CRC screening. This
      legitimized its use and offered even further encouragement to seniors, who may
      have been reluctant to undergo the procedure because of the non-pecuniary risks
      associated with it. In addition, 37 CRC screening interventions occurred during
      this timeframe to enhance compliance with screening standards. Using multilevel
      analysis of individuals' endoscopy utilization, derived from 100% FFS Medicare
      claims, along with county-level market and contextual factors, we compare the
      periods before and after the MMA (2001-2005 to 2006-2009) to determine whether
      disparities in the utilization of endoscopic CRC screening occurred or changed
      over the decade. We examined Blacks, Asians, and Hispanics relative to Whites,
      and Females relative to Males (with race or ethnicity combined). We examined each
      state separately for evidence of disparities within states, to avoid confounding
      by geographic disparities. We expected that the net effect of the policy changes
      and the targeted interventions over the decade would be to increase CRC screening
      by endoscopy, reducing disparities. We saw improvements over time (reduced
      disparities relative to Whites) for Blacks and Hispanics residing in several
      states, and improvements over time for Females relative to Males in many states.
      For the vast majority of states, however, disparities persisted with Whites and
      Males exhibiting greater rates of utilization than other groups. States that
      undertook the interventions were more likely to have had improvements in
      disparities or positive disparities for women and minorities. While some gains
      were made over this time period, the gains were unevenly distributed across the
      USA and more work needs to be done to reduce remaining disparities.

PMID- 30232794
TI  - Health-seeking behaviour and treatment delay in patients with pulmonary
      tuberculosis in Switzerland: some slip through the net.
AB  - AIMS OF THE STUDY: To assess the health-seeking behaviour, the patient delay
      (onset of symptoms to first consultation) and the health system delay (first
      consultation to start of tuberculosis treatment) among patients with pulmonary
      tuberculosis (TB) diagnosed in Switzerland, and to assess the predictors of the
      various types of delay. METHODS: A survey among pulmonary TB patients was carried
      out in six cantons, covering 42% of all pulmonary adult TB cases notified in
      Switzerland. Data were collected by collaborators of the cantonal lung
      associations in charge of the follow-up of TB patients to investigate treatment
      seeking behaviour and to establish various delays and its predictors. Predictors
      of percentiles of delay (median and 75th percentile) were assessed using quantile
      regression. RESULTS: Among 252 eligible patients, 162 patients could be
      interviewed. Of these, 20.4% were born in Switzerland. Cough as a symptom was
      mentioned by 76% of the interviewed patients. Almost half of the 162 patients
      (46%) consulted first a general practitioner in an ambulatory care setting and
      26% approached a hospital first. The median delay between symptom onset and first
      healthcare contact (patient delay) was 5.2 weeks, which is slightly longer than
      findings in other low prevalence countries. The interquartile range was 1.6 to
      14.2 weeks. The median delay between first consultation in Switzerland and the
      start of TB treatment (health system delay) was 2 weeks. The interquartile range
      was 0.6 to 7.1 weeks. There were no clear predictors of patient delay. The main
      predictors of a longer median health system delay were the presence of fever (1.6
      weeks, 95% confidence interval [CI] 0.5 to 2.6 weeks), having visited first a
      general practitioner or a paediatrician (1 week, 95% CI 0.1 to 1.9 weeks) and
      having seen three or four doctors before beginning TB treatment (2.9 weeks, 95%
      CI 0.7 to 5.1 weeks). A clear predictor of a shorter median health system delay
      was having undergone an X-ray at the first consultation (-2.9 weeks, 95% CI -4.8
      to -0.9 weeks). Marginally significant for shorter delay was male sex (-2.6
      weeks, 95% CI -5.4 to 0.1 weeks). CONCLUSIONS: No predictor of patient delay was
      found among the variables collected. For one fourth of the patients, the health
      system delay was longer than 7 weeks. General practitioners are commonly
      approached first, and they have to consider TB, also for patients not considered
      at high-risk for TB.

PMID- 30232795
TI  - Coercion in substance use disorders: clinical course of compulsory admissions in
      a Swiss psychiatric hospital.
AB  - According to the Swiss legal system, involuntary admission is one of the farthest
      reaching incursions into personal autonomy. The effect of compulsory admission in
      treatment of substance use disorders (SUDs) on variables such as length of stay
      or leaving treatment before recommended discharge remains elusive. In order to
      elucidate these effects, we retrospectively analysed the clinical course of
      treatment of 608 patients who were admitted between November 2016 and October
      2017 to the Department of Addictive Disorders of the canton of Aargau.
      Involuntarily admitted patients showed lower health and social functioning, as
      measured by the Health of the Nation Outcome Scales (HoNOS), compared with those
      with voluntary status. In involuntary admissions for SUD treatment, length of
      stay was significantly shorter and the proportion of patients who left treatment
      against recommendation was twice as high as in voluntarily admitted patients.
      Furthermore, if treatment was initiated on a compulsory basis, a subsequent
      switch to voluntary treatment status appeared to be very uncommon. We conclude
      that, at least in involuntary admission according to the Swiss legal system,
      these admissions do not lead to sustained inpatient treatment.

PMID- 30232796
TI  - [Effects of hypotherapy on the motor function of persons with Down's syndrome: a
      systematic review].
AB  - INTRODUCTION: Down's syndrome is the main cause of intellectual disability and
      the most common human genetic alteration. Motor impairments are among the most
      important alterations presented by Down's syndrome subjects. Hippotherapy is a
      treatment on and with a horse, and it is currently being used as a therapy to
      correct those dysfunctions. AIM: To review published research literature on the
      effect exerted by hippotherapy on the gross motor function of people with Down's
      syndrome. SUBJECTS AND METHODS: The bibliography in the following databases has
      been widely searched: CINAHL, Medline, The Cochrane Library, PEDro, Scopus, and
      Web of Science. The journals Fisioterapia and Cuestiones de Fisioterapia have
      also been consulted. The electronic literature search strategy was addressed in
      two thematic fields: Down's syndrome and hippotherapy. Studies selection was
      carried out following inclusion and exclusion criteria and rejecting duplicate
      papers. That search included articles published between 2000 and 2016. RESULTS:
      For this work, 23 articles were found, 15 of which were discarded for different
      reasons, leaving 8 valid ones. CONCLUSIONS: There is no strong evidence on the
      improvement of gross motor function in people with Down's syndrome after
      treatment with hippotherapy. More studies with higher methodological quality, are
      needed to verify the effectiveness of hippotherapy in the treatment of gross
      motor function in subjects with Down's syndrome.

PMID- 30232797
TI  - [Signs predicting early growth of intracerebral haemorrhage in computer
      tomography without enhancement and mortality].
AB  - INTRODUCTION: Intracerebral haemorrhage is associated with high morbidity and
      mortality, and an increase in its volume in the early phases entails a poorer
      prognosis. The blend sign, the heterogeneous density, the irregular morphology
      and a fluid level in the haematoma are related to an early growth of the
      haematoma. AIM: To determine whether these four characteristics are associated
      with greater mortality at 7, 30 and 90 days of the occurrence of the
      intracerebral haemorrhage. PATIENTS AND METHODS: A retrospective cohort study
      that included all the patients attended in our hospital between 2010 and 2015 for
      spontaneous intracerebral haemorrhage with a computed tomography brain scan
      performed in the first six hours following the onset of symptoms. RESULTS: Of the
      158 patients included in the sample, 23 (14.6%) presented blend sign; 39 (24.7%),
      heterogeneity; 53 (33.5%), irregularity; and 33 (20.9%), fluid level. In the
      bivariate analysis, only heterogeneity and irregularity were associated with
      increased mortality at 7, 30 and 90 days. In the multivariate logistic regression
      analysis, previous treatment with an antiplatelet drug, a score on the Glasgow
      Coma Scale below 13 and irregularity were associated with higher mortality in the
      first seven days. CONCLUSION: The study shows an association between irregularity
      of the haematoma and mortality in the first seven days. Irregularity would allow
      identification of patients with a more unfavourable prognosis; in these cases,
      strict surveillance, especially of factors related to the growth of the
      haematoma, could improve their prognosis.

PMID- 30232798
TI  - [Epidemiology of epilepsy in Spain and Latin America].
AB  - INTRODUCTION: The connection between Spain and Latin America on the cultural,
      ethnic and commercial levels has been very important over the last five
      centuries, and this accounts for the existence of a common identity that can
      condition the epidemiology of chronic diseases with genetic and environmental
      determinants, such as epilepsy. In the last 15 years significant changes have
      come about in the economic development and the healthcare conditions in these
      countries as well as the migratory flows among them that may have brought about
      changes in the previous epidemiological situation. We present an exhaustive
      review of the epidemiological studies describing the status of epilepsy in Spain
      and Latin America. DEVELOPMENT: A bibliographic search was conducted of
      descriptive epidemiology studies about epilepsy in Spain and in each of the
      countries of Latin America. The methodology and quality of each study are
      reviewed and data on prevalence and incidence are extracted for each country. A
      total of 796 studies are evaluated, of which 55 (48 on prevalence and seven on
      incidence) meet eligibility criteria. CONCLUSIONS: There is no evidence of a
      variation in the epidemiological situation of epilepsy in Latin America. Some
      prevalence and incidence rates are still higher than in western countries. This
      difference is especially apparent in countries where cysticercosis is endemic and
      is inversely proportional to the wealth of the country, measured by the per
      capita gross domestic product. There is no evidence of any change in the
      epidemiology of epilepsy in Spain despite the migratory flows of countries with a
      high prevalence of epilepsy in recent years.

PMID- 30232799
TI  - Role of major long fiber tracts association in empathy.
AB  - INTRODUCTION: The empathic capacity is a field of research that has been studied
      from various disciplines such as psychology, philosophy, or ethology and recently
      the field of neuroscience has been added. Thus, there has been an increase in
      studies using structural and functional neuroimaging, which has allowed to
      establish the brain structures that underlie its functioning. On the other hand,
      the appearance of measurement instruments such as diffusion tensor, have allowed
      us to begin to understand the role of white matter and neural connectivity in
      empathy. AIM: To review the results obtained from the relation of the long fiber
      tracts of association with the functions associated with the empathic capacity.
      Emphasis is placed on the division of empathy into its cognitive and affective
      components. DEVELOPMENT: The scientific literature has been revised using the
      Google Scholar, Science Research, Chemedia, PubMed, Dialnet and Teseo search
      engines. CONCLUSIONS: Both the functions associated with empathic capacity and
      empathy itself appear to be related to white matter fascicles. Likewise, in
      disorders characterized by a deficit in empathy, a relationship is suggested
      between the white matter tracts and alterations in important functions so that
      the empathic capacity dies. In this sense, the white matter tracts most related
      to empathy are the fronto-occipital fasciculus, the inferior longitudinal
      fasciculus, the superior longitudinal fasciculus and the uncinate fasciculus.
      Considering these results, it could be argued that neuronal connectivity,
      independently of structural and functional aspects, could play an important role
      in empathic function.

PMID- 30232800
TI  - [XXI Reunion Anual de la Sociedad Neurologica Asturiana. Communications].

PMID- 30232801
TI  - [Meningeal syndrome in a patient treated with a combination of immune checkpoint
      inhibitors for a metastatic melanoma].

PMID- 30232802
TI  - CE-MS for metabolomics: Developments and applications in the period 2016-2018.
AB  - In the field of metabolomics, CE-MS is now recognized as a strong analytical
      technique for the analysis of (highly) polar and charged metabolites in a wide
      range of biological samples. Over the past few years, significant attention has
      been paid to the design and improvement of CE-MS approaches for (large-scale)
      metabolic profiling studies and for establishing protocols in order to further
      expand the role of CE-MS in metabolomics. In this paper, which is a follow-up of
      a previous review paper covering the years 2014-2016 (Electrophoresis 2017, 38,
      190-202), main advances in CE-MS approaches for metabolomics studies are outlined
      covering the literature from July 2016 to June 2018. Aspects like developments in
      interfacing designs and data analysis tools for improving the performance of CE
      MS for metabolomics are discussed. Representative examples highlight the utility
      of CE-MS in the fields of biomedical, clinical, microbial, and plant
      metabolomics. A complete overview of recent CE-MS-based metabolomics studies is
      given in a table, which provides information on sample type and pretreatment,
      capillary coatings and MS detection mode. Finally, some general conclusions and
      perspectives are given.

PMID- 30232803
TI  - Risk-based decision making in transfusion medicine.
AB  - Formal processes to assess risk are well established in numerous areas of society
      including the environment, transportation, energy and food production sectors as
      well as some areas of health care such as new drugs or other therapeutic goods.
      However, these processes and their associated frameworks have only recently come
      to be used to make decisions in blood transfusion practice or in blood system
      policy development. This review describes the evolution of the use of risk-based
      decision making and discusses the elements that should be considered in its
      application to blood system issues. Following the identification and
      characterization of the risk, a structured process is undertaken to assess the
      magnitude of the risk and the level of risk reduction that can reasonably be
      achieved in the context of the complexity of the risk management action proposed
      and its cost. Inputs must be sought from appropriate subject matter experts, but
      also from those who can consider issues of ethics and social values. Engagement
      of the public is an essential step. Proposed interventions should be assessed for
      their likelihood of mitigating the risk and the proportional resource allocation
      in comparison with similar risks to the blood system or health system. Examples
      are provided of how a risk-based decision-making framework is used to address
      identified risks in the blood system.

PMID- 30232804
TI  - Age,sex, but not ATP7B genotype effectively influences the clinical phenotype of
      Wilson disease.
AB  - : Wilson disease (WD) is an inherited disorder of hepatic copper metabolism with
      considerable variation in clinical presentations, the most common ones being
      liver disease and neuropsychiatric disturbances. This study investigated the
      clinical presentation in relation to mutations in a large cohort of WD patients.
      PATIENTS AND METHODS: 1357 patients (702 children, 655 adults; 1172 index
      patients, 185 siblings, all with a Leipzig score >= 4, male/female:679/678) were
      studied. The age and the symptoms at presentation were used as key phenotypic
      markers. Index patients were clinically classified either as having hepatic
      (n=711) or neurologic disease (n=461). 708 (52.8%) patients had a liver biopsy at
      diagnosis. DNA was sequenced by the Genetic Analyzers ABI Prism 310 (Perkin
      Elmer) or 3500 (Applied Biosystems). MAJOR FINDINGS: 1.Three hundred ninety four
      different mutation combinations were detected. The most frequent mutation was
      H1069Q (c.3207C>A; allele frequency: 46.9%), followed by P767P-fs (c.2304dupC;
      2.85%), P1134P-fs (c.3402delC; 2.8%), and R969Q (c.2755C>T; 2.18%). 2.There was
      no correlation between mutations and individual clinical manifestation. 3.There
      was a gender effect in index patients: hepatic presentation was more common in
      females (m/f: 328/383) and neurologic presentation in males (259/202; p<0.001).
      4.At diagnosis already 39.5% of children/adolescents ( 18) but 58% of adults had
      cirrhosis. The presence of cirrhosis did not correlate with the genotype.
      CONCLUSION: These findings refine and extend our understanding of the natural
      history and individual spectrum/manifestations of WD. Initially, there is
      asymptomatic hepatic involvement which may progress and become symptomatic.
      Neurologic symptoms present many years later. This article is protected by
      copyright. All rights reserved.

PMID- 30232805
TI  - Cognition and Incarceration: Cognitive Impairment and Its Associated Outcomes in
      Older Adults in Jail.
AB  - OBJECTIVES: To determine prevalence of, and outcomes associated with, a positive
      screen for cognitive impairment in older adults in jail. DESIGN: Combined data
      from cross-sectional (n=185 participants) and longitudinal (n=125 participants)
      studies. SETTING: Urban county jail. PARTICIPANTS: Individuals in jail aged 55
      and older (N = 310; mean age 59, range 55-80). Inclusion of individuals aged 55
      and older is justified because the criminal justice system defines "geriatric
      prisoners" as those aged 55 and older. MEASUREMENTS: Baseline and follow-up
      assessments of health, psychosocial factors, and cognitive status (using the
      Montreal Cognitive Assessment (MoCA)); 6-month acute care use and repeat arrest
      assessed in those followed longitudinally. RESULTS: Participants were of low
      socioeconomic status (85% annual income < $15,000) and predominantly nonwhite
      (75%). Many (70%) scored less than 25 on the MoCA; those with a low MoCA score
      were more likely to be nonwhite (81% vs 62%, p<.001) and report fair or poor
      health (54% vs 41%, p=.04). Over 6 months, a MoCA score of less than 25 was
      associated with multiple emergency department visits (32% vs 13%, p=.02),
      hospitalization (35% vs 16%, p=.03), and repeat arrests (45% vs 21%, p=.01).
      CONCLUSIONS: Cognitive impairment is prevalent in older adults in jail and is
      associated with adverse health and criminal justice outcomes. A geriatric
      approach to jail-based and transitional health care should be developed to assess
      and address cognitive impairment. Additional research is needed to better assess
      cognitive impairment and its consequences in this population. J Am Geriatr Soc
      66:2065-2071, 2018.

PMID- 30232806
TI  - HMGB3 promotes the proliferation and metastasis of glioblastoma and is negatively
      regulated by miR-200b-3p and miR-200c-3p.
AB  - High mobility group box 3 (HMGB3) is strongly involved in oncogenesis in a
      variety of cancers. In the present study, we have explored the role of HMGB3 in
      glioblastoma multiforme (GBM) tumorigenesis and have identified the microRNAs
      (miRNAs) miR-200b-3p and miR-200c-3p as negative regulators of HMGB3 expression.
      We began by determining that endogenous HMGB3 expression levels were
      significantly elevated in GBM tissues and in 3 GBM cell lines. To study the
      function of HMGB3 in GBM, we transfected a small-interfering RNA (siRNA) against
      HMGB3 into GBM cell lines U251 and LN229. MTT and tumour sphere assays
      demonstrated that HMGB3 knockdown significantly inhibited cell proliferation.
      Wound healing and transwell assays determined that HMGB3 knockdown substantially
      suppressed GBM cell migration and invasion. We evaluated the effects of HMGB3
      knockdown on MAPK phosphorylation and target gene expression, finding that HMGB3
      knockdown significantly reduced MAPK phosphorylation (p-ERK (1/2), p-p38, and p
      JNK). We then used the biologic prediction algorithm TargetScan to identify the
      3' untranslated region (3'-UTR) of HMGB3 as a target of miR-200b-3p and miR-200c
      3p. Luciferase, qRT-PCR, and western blot assays confirmed that miR-200b-3p and
      miR-200c-3p bind and inhibit HMGB3 expression. Finally, Pearson correlation
      analyses demonstrated a negative correlation between relative HMGB3 mRNA and miR
      200b/c-3p expression levels in GBM tissue samples. Overall, the present study
      strongly suggests that HMGB3 promotes GBM oncogenesis through the MAPK signalling
      pathway while miR-200b-3p and miR-200c-3p inhibit its expression.

PMID- 30232807
TI  - Turnaround in the history of carotid chemoreflex contribution to
      cardiorespiratory control in COPD: what are the upcoming chapters?

PMID- 30232808
TI  - Rank-based inference for covariate and group effects in clustered data in
      presence of informative intra-cluster group size.
AB  - There have been numerous attempts to extend the Wilcoxon rank-sum test to
      clustered data. Recently, one such rank-sum test (Dutta & Datta, 2016, Biometrics
      72, 432-440) was developed to compare the group-specific marginal distributions
      of outcomes in clustered data where the conditional distributions of outcomes
      depend on the number of observations from that group in a given cluster, a
      phenomenon referred to as informative intra-cluster group (ICG) size. However,
      comparison of group-specific marginal distributions may not be sufficient in
      presence of some potentially useful covariables that are observed in the study.
      In addition, not accounting for the effect of these covariates can lead to biased
      and misleading inference for the group comparisons. Thus, the purpose of this
      article is twofold. First, we develop a method to estimate the covariate effects
      using rank-based weighted estimating equations that are appropriate when the ICG
      size is informative. Second, we construct an aligned rank-sum test based on the
      covariate adjusted outcomes. Asymptotic distributions of the R-estimators and the
      test statistic are provided. Through simulation studies, we show the importance
      of selecting proper weights in constructing the estimating equations when
      informativeness is present through the cluster or ICG sizes. We also demonstrate
      the superiority and the robustness of our method in comparison to regular
      parametric linear mixed models in clustered data. We apply our method to analyze
      different real-life data sets including a data on birthweights of rat pups in
      different litters and a dental data on tooth attachment loss.

PMID- 30232809
TI  - Occupational asthma associated with bleached chlorine-free cellulose dust in a
      sanitary pad production plant.
AB  - BACKGROUND: Cellulose is an insoluble plant polysaccharide produced from soft
      wood pulp. Although chronic respiratory effects associated with high cellulose
      based dust levels have been previously described, occupational asthma has not. A
      37 year old machine operator in a sanitary pad production factory presented with
      new-onset work-related asthma symptoms for two years. METHODS: The worker
      underwent clinical, pulmonological and immunological (skin prick tests, serum
      specific IgE determinations) evaluation using standardised procedures. The
      cellulose product was subjected to scanning electron microscopy (SEM)
      examination. A specific inhalation challenge test performed with the cellulose
      product ensured that dust concentrations were kept below 5 mg/m3 . RESULTS: The
      subject was not atopic and did not have elevated IgE to pine wood or xylanase.
      The cellulose product appeared to be free of protein contaminants on SEM. The
      Work Effect Index computed on serial PEF recordings was elevated (WEI =
      3.8).Specific inhalational challenge with the cellulose product dust revealed a
      late bronchial response (39% drop in FEV1 at 3 hours post challenge). CONCLUSION:
      This is the first reported case of occupational asthma to a cellulose fibre
      product. A non-specific immune reaction or irritant response seems likely. These
      fibres may therefore not be biologically inert. The occupational exposure limit
      of 10 mg/m3 generally used for cellulose dust appears to be non-protective.

PMID- 30232810
TI  - Teriflunomide's Effect on Glia in Experimental Demyelinating Disease: A
      Neuroimaging and Histologic Study.
AB  - BACKGROUND AND PURPOSE: Teriflunomide reduces disability progression and brain
      atrophy in multiple sclerosis patients. The exact mechanism of action by which
      teriflunomide exerts these effects is currently unknown. We assessed the effect
      of teriflunomide on brain glial cells in the Theiler's murine encephalomyelitis
      virus (TMEV) by using a histological approach in combination with neuroimaging.
      METHODS: Forty-eight SJL female mice received an intracerebral injection of TMEV
      at 6-8 weeks of age and were then treated with teriflunomide (n = 24) or placebo
      (n = 24) for 9 months. They were examined with MRI and behavioral testing at 2,
      6, and 9 months postinduction (mPI). Of those, 18 teriflunomide-treated and 17
      controls mice were analyzed histologically at 9 mPI to sample from different
      brain regions for myelination status, microglial density, and oligodendroglial
      lineage. The histological and MRI outcomes were correlated. RESULTS: Corpus
      callosum microglial density was numerically lower in the teriflunomide-treated
      mice compared to the control group (141.1 +/- 21.7 SEM vs. 214.74 +/- 34.79 SEM,
      Iba1+ cells/mm2 , P = .087). Basal ganglia (BG) microglial density in the
      teriflunomide group exhibited a negative correlation with fractional anisotropy
      (P = .021) and a positive correlation with mean diffusivity (P = .034),
      indicating less inflammation and axonal damage. Oligodendroglial lineage cell and
      myelin density were not significantly different between treatment groups.
      However, a significant positive correlation between BG oligodendrocytes and BG
      volume (P = .027), and with N-acetyl aspartate concentration (P = .008), was
      found in the teriflunomide group, indicating less axonal loss. CONCLUSION:
      Teriflunomide altered microglia density and oligodendrocytes differentiation,
      which was associated with less evident microstructural damage on MRI.

PMID- 30232811
TI  - Resolving the roles of the Rhodobacter sphaeroides HemA and HemT 5-aminolevulinic
      acid synthases.
AB  - Strains of the phototrophic alpha-proteobacterium Rhodobacter sphaeroides vary in
      the number of enzymes catalyzing the formation of 5-aminolevulinic acid (ALA
      synthases) that are encoded in their genomes. All have hemA, but not all have
      hemT. This study compared transcription of these genes, and also properties of
      their products among three wild-type strains; 2.4.3 has hemA alone, 2.4.1 and
      2.4.9 have both hemA and hemT. Using lacZ reporter plasmids all hemA genes were
      found to be upregulated under anaerobic conditions, but induction amplitudes
      differ. hemT is transcriptionally silent in 2.4.1 but actively transcribed in
      2.4.9, and strongly upregulated under anaerobic-dark growth conditions when cells
      are respiring dimethyl sulfoxide, vs. aerobic-dark or phototrophic (anaerobic
      light) conditions. Two extracytoplasmic function (ECF)-type sigma factors present
      in 2.4.9, but absent from 2.4.1 are directly involved in hemT transcription.
      Kinetic properties of the ALA synthases of all three strains were similar, but
      HemT enzymes are far less sensitive to feedback inhibition by hemin than HemA
      enzymes, and HemT is less active under oxidizing conditions. A model is presented
      that compares and contrast events in strains 2.4.1 and 2.4.9.

PMID- 30232812
TI  - A transcriptomic investigation of appetite-regulation and digestive processes in
      giant grouper Epinephelus lanceolatus during early larval development.
AB  - The giant grouper Epinephelus lanceolatus is an ecologically vulnerable species
      with high market demand. However, efforts to improve larval husbandry are
      hindered by a lack of knowledge surrounding larval developmental physiology. To
      address this shortfall, a transcriptomic approach was applied to larvae between 1
      and 14 days post hatch (dph) to characterise the molecular ontogenesis of genes
      that influence appetite and digestion. Appetite regulating factors were detected
      from 1 dph, including neuropeptide Y, nesfatin-1, cocaine and amphetamine
      regulated transcript, cholecystokinin and pituitary adenylate cyclase activating
      peptide and the expression level of several genes changed sharply with the onset
      of exogenous feeding. The level of expression for proteases, chitinases, lipases
      and amylases typically followed one of two expression patterns, a general
      increase as development progressed, or an inverted U-shape with maximal
      expression at c. 6 dph. Similarly, the tendency among both expression patterns
      was for the level of expression to increase around the time of mouth-opening.
      There was also evidence to suggest the presence of putative isoforms for several
      digestion-related genes. We have provided an insight into appetite-regulation and
      digestive processes in groupers during early larval development and have
      developed a transcriptomic database that will aid future efforts to rear this
      species in an aquaculture setting.

PMID- 30232813
TI  - A Plea for Clinically Oriented Anatomy.

PMID- 30232814
TI  - Increased immunoreactivity for TRPM8 in cutaneous squamous cell carcinoma.

PMID- 30232815
TI  - Microfluidic thread-based electrode system to detect glucose and
      acetylthiocholine.
AB  - A reusable and simple to fabricate electrochemical sensor for the detection of
      glucose and acetylthiocholine using thread-based electrodes and nylon thread is
      described. The fabrication of the device consisted of two steps. First, three
      nylon-based electrodes (reference, working, and counter) were painted with one
      layer of conductive inks (silver and carbon ink, or silver/silver chloride ink).
      The electrodes were taped onto parafilm, and a piece of white nylon thread was
      wrapped around each electrode connecting the three electrodes. For the glucose
      system, a PBS solution containing glucose oxidase (GOx) (10 mg/mL), and potassium
      ferricyanide (K3 [Fe(CN)6 ]) (10 mg/mL) as mediator, was dried onto the thread,
      and increasing concentrations of glucose (0-15 mM) was added to the thread and
      measured by cyclic voltammetry (CV). The current output from the glucose
      oxidation was proportional to the concentration of glucose. For the second
      system, a solution of acetylcholinesterase (AChE) (0.08 U/mL) in PBS was added to
      the nylon thread, and increasing concentrations of acetylthiocholine (ATC) (0
      9.84 mg/mL) was added and measured by CV. The current output from the oxidation
      of thiocholine (produced by AChE reacting with ATC) was proportional to the
      concentrations of ATC added to the thread. From both systems, a graph of current
      output versus substrate concentration was produced and fitted with a linear
      regression line that gave R2 values of 0.985 (GOX /glucose) and 0.995 (AChE/ATC).

PMID- 30232816
TI  - Relationship between incidence and prevalence in psychotic disorders: An
      incidence-prevalence-mortality model.
AB  - OBJECTIVES: Incidence-prevalence-mortality (IPM) models have been developped to
      estimate incidence or prevalence when one of these two measures is unavailable.
      We aimed to test the consistency of an IPM model of psychotic disorders on a
      recent incidence-prevalence couple dataset and to identify potential causes of
      inconsistency by applying the model to (a) the whole population, (b) female and
      male subgroups, (c) migrant subgroups, and (d) psychotic disorders with age at
      onset (AAO) between 18 and 24 (18-24 AAO). METHODS: We modelled prevalence (MP)
      using incidence data and the expected mortality and remission values. We then
      compared the MP to the observed prevalence (OP). RESULTS: In the whole
      population, the model significantly underestimated the prevalence (MP = 3.30, 95%
      CI [2.97, 3.66]; OP = 4.98, 95% CI [4.58, 5.41]). The results were similar for
      the two genders. In the migrants group, results were in the opposite direction,
      the model significantly overestimating the prevalence. Finally, in the 18-24 AAO
      subgroup, the model performed well, with OP and MP not significantly different.
      CONCLUSION: These results suggest that standard IPM models do not perform well
      for psychotic disorders and more complex models taking into account the
      heterogeneity of the sample (in terms of remission, mortality, population
      movements, etc.) need to be developed.

PMID- 30232817
TI  - Short-term and long-term human or mouse organoid units generate tissue-engineered
      small intestine without added signalling molecules.
AB  - NEW FINDINGS: What is the central question of this study? Tissue-engineered small
      intestine was previously generated in vivo by immediate implantation of organoid
      units derived from both mouse and human donor intestine. Although immediate
      transplantation of organoid units into patients shows promise as a potential
      future therapy, some critically ill patients might require delayed
      transplantation. What is the main finding and its importance? Unlike enteroids,
      which consist of isolated intestinal crypts, short- and long-term cultured
      organoid units are composed of epithelial and mesenchymal cells derived from
      mouse or human intestine. Organoid units do not require added signalling
      molecules and can generate tissue-engineered intestine in vivo. ABSTRACT: Mouse
      and human postnatal and fetal organoid units (OUs) maintained in either short
      term culture (2 weeks) or long-term culture (from 4 weeks up to 3 months) without
      adding exogenous growth factors were implanted in immunocompromised mice to form
      tissue-engineered small intestine (TESI) in vivo. Intestinal epithelial stem and
      neuronal progenitor cells were maintained in long-term OU cultures from both
      humans and mice without exogenous growth factors, and these cultures were
      successfully used to form TESI. This was enhanced with OUs derived from human
      fetal tissues. Organoid unit culture is different from enteroid culture, which is
      limited to epithelial cell growth and requires supplementation with R-Spondin,
      noggin and epidermal growth factor. Organoid units contain multiple cell types,
      including epithelial, mesenchymal and enteric nervous system cells. Short- and
      long-term cultured OUs derived from mouse and human intestine develop into TESI
      in vivo, which contains key components of the small intestine similar to native
      intestine.

PMID- 30232818
TI  - ETFDH Mutations and Flavin Adenine Dinucleotide Homeostasis Disturbance Are
      Essential for Developing Riboflavin-Responsive Multiple Acyl-Coenzyme A
      Dehydrogenation Deficiency.
AB  - OBJECTIVE: Riboflavin-responsive multiple acyl-coenzyme A dehydrogenation
      deficiency (RR-MADD) is an inherited fatty acid metabolism disorder mainly caused
      by genetic defects in electron transfer flavoprotein-ubiquinone oxidoreductase
      (ETF:QO). The variant ETF:QO protein folding deficiency, which can be corrected
      by therapeutic dosage of riboflavin supplement, has been identified in HEK-293
      cells and is believed to be the molecular mechanism of this disease. To verify
      this hypothesis in vivo, we generated Etfdh (h)A84T knockin (KI) mice. METHODS:
      Tissues from these mice as well as muscle biopsies and fibroblasts from 7 RR-MADD
      patients were used to examine the flavin adenine dinucleotide (FAD) concentration
      and ETF:QO protein amount. RESULTS: All of the homozygous KI mice (Etfdh
      (h)A84T/(h)A84T , KI/KI) were initially normal. After being given a high-fat and
      vitamin B2 -deficient (HF-B2 D) diet for 5 weeks, they developed weight loss,
      movement ability defects, lipid storage in muscle and liver, and elevated serum
      acyl-carnitine levels, which are clinically and biochemically similar to RR-MADD
      patients. Both ETF:QO protein and FAD concentrations were significantly decreased
      in tissues of HF-B2 D-KI/KI mice and in cultured fibroblasts from RR-MADD
      patients. After riboflavin treatment, ETF:QO protein increased in proportion to
      elevated FAD concentrations, but not related to mRNA levels. These results were
      further confirmed in cultured fibroblasts from RR-MADD patients. INTERPRETATION:
      For the first time, we successfully developed a RR-MADD mice model and confirmed
      that FAD homeostasis disturbances played a crucial role on the pathomechanism of
      RR-MADD in this mouse model and culture cells from patients. Supplementation of
      riboflavin may stabilize variant ETF:QO protein by rebuilding FAD homeostasis.
      Ann Neurol 2018;84:667-681.

PMID- 30232820
TI  - Estimating heterogeneous treatment effects for latent subgroups in observational
      studies.
AB  - Individuals may vary in their responses to treatment, and identification of
      subgroups differentially affected by a treatment is an important issue in medical
      research. The risk of misleading subgroup analyses has become well known, and
      some exploratory analyses can be helpful in clarifying how covariates potentially
      interact with the treatment. Motivated by a real data study of pediatric kidney
      transplant, we consider a semiparametric Bayesian latent model and examine its
      utility for an exploratory subgroup effect analysis using secondary data. The
      proposed method is concerned with a clinical setting where the number of
      subgroups is much smaller than that of potential predictors and subgroups are
      only latently associated with observed covariates. The semiparametric model is
      flexible in capturing the latent structure driven by data rather than dictated by
      parametric modeling assumptions. Since it is difficult to correctly specify the
      conditional relationship between the response and a large number of confounders
      in modeling, we use propensity score matching to improve the model robustness by
      balancing the covariates distribution. Simulation studies show that the proposed
      analysis can find the latent subgrouping structure and, with propensity score
      matching adjustment, yield robust estimates even when the outcome model is
      misspecified. In the real data analysis, the proposed analysis reports
      significant subgroup effects on steroid avoidance in kidney transplant patients,
      whereas standard proportional hazards regression analysis does not.

PMID- 30232819
TI  - Interspace between Popliteal Artery and posterior Capsule of the Knee (IPACK)
      Injectate Spread: A Cadaver Study.
AB  - OBJECTIVES: Local anesthetic injection into the interspace between the popliteal
      artery and the posterior capsule of the knee (IPACK) has the potential to provide
      motor-sparing analgesia to the posterior knee after total knee arthroplasty. The
      primary objective of this cadaveric study was to evaluate injectate spread to
      relevant anatomic structures with IPACK injection. METHODS: After receipt of
      Institutional Review Board Biospecimen Subcommittee approval, IPACK injection was
      performed on fresh-frozen cadavers. The popliteal fossa in each specimen was
      dissected and examined for injectate spread. RESULTS: Ten fresh-frozen cadaver
      knees were included in the study. Injectate was observed to spread in the
      popliteal fossa at a mean +/- SD of 6.1 +/- 0.7 cm in the medial-lateral
      dimension and 10.1 +/- 3.2 cm in the proximal-distal dimension. No injectate was
      noted to be in contact with the proximal segment of the sciatic nerve, but 3
      specimens showed injectate spread to the tibial nerve. In 3 specimens, the
      injectate showed possible contact with the common peroneal nerve. The middle
      genicular artery was consistently surrounded by injectate. CONCLUSIONS: This
      cadaver study of IPACK injection demonstrated spread throughout the popliteal
      fossa without proximal sciatic involvement. However, the potential for injectate
      to spread to the tibial or common peroneal nerve was demonstrated. Consistent
      surrounding of the middle genicular artery with injectate suggests a potential
      mechanism of analgesia for the IPACK block, due to the predictable relationship
      between articular sensory nerves and this artery. Further study is needed to
      determine the ideal site of IPACK injection.

PMID- 30232821
TI  - Choroidal thinning and ocular electrophysiology in a case of vascular cognitive
      impairment after stroke.

PMID- 30232822
TI  - Patients' experiences of coping with multiple chronic conditions: A meta
      ethnography of qualitative work.
AB  - Multiple chronic conditions (MCCs) pose a major and growing burden on the
      individuals' health. The ways in which people cope with their stresses related to
      their chronic conditions are significant to their health outcomes. This review
      sought to understand lived experiences of coping with MCCs by a meta-ethnography
      of qualitative studies. Twenty-six studies were identified in four electronic
      databases including PubMed, PsycINFO, EMBASE, and CINAHL that were searched from
      1966 to 2017. A seven-step analytic method was used after a quality evaluation
      based on Joanna Briggs Institute Qualitative Assessment and Review Instrument
      (JBI-QARI). The findings illustrated that experiences of coping with MCCs were
      interacted with (i) appraisals of MCCs, (ii) strategies to maintain a normal
      life, (iii) strategies to keep the spirits up, and (iv) coping in the social
      context. To sum up, this review provided a collection of narratives on coping
      with MCCs. The findings would help to recognize the high complexity experienced
      by these patients, also potentially offered a foundation for the design of a
      feasible intervention to more optimally highlight the demands of managing MCCs.

PMID- 30232823
TI  - Application of biclustering algorithm in adverse drug reaction monitoring system
      of China.
AB  - PURPOSE: Signal evaluation is considered to be a tedious process owing to the
      large number of disproportional signals detected. This study aimed to apply a
      biclustering algorithm in the spontaneous reporting system of China and to obtain
      the optimal parameters. The biclustering algorithm is expected to improve the
      efficiency of signal evaluation by identifying similar signal groups. METHODS:
      Information component (IC) was the method used for disproportionality analysis.
      By using IC thresholds of various strengths (0.05-4.00), the original
      quantitative data matrix was transformed into 80 different binary data matrices,
      where each cell contained either a 1 or 0. The biclustering results were obtained
      using a total of 720 Bimax algorithm parameters (minimal number of columns and
      rows was 3, 4, or 5). Next, the optimal parameters were determined through the
      comprehensive evaluation of the rank sum ration. Finally, we examined the
      biclustering results under the optimal parameters and evaluated the effect of
      biclustering analysis on adverse drug reaction (ADR) data in China. RESULTS: The
      optimal strength of the IC threshold was 0.80, and the minimum number of rows and
      columns was 3. After taxonomic evaluation, we also found that 1836 biclusters
      (42.8%) contained similar drugs or similar ADRs, which accounted for 72.3% of
      signals unevaluated. CONCLUSIONS: Applying biclustering analysis in spontaneous
      reporting system could provide support in confirming unrecognized ADRs,
      identifying rare ADRs, and screening drug-ADR pairs, which need more attention.
      Biclustering algorithm could improve the efficiency of signal detection and
      evaluation in China.

PMID- 30232824
TI  - Paclitaxel-eluting balloon versus everolimus-eluting stent in patients with
      diabetes mellitus and in-stent restenosis: Insights from the randomized DARE
      trial.
AB  - OBJECTIVES: To investigate the relative performance of treatment with a
      paclitaxel-eluting balloon (PEB) compared with an everolimus-eluting stent (EES)
      for in-stent restenosis (ISR) in patients with diabetes mellitus (DM).
      BACKGROUND: ISR remains a challenge in contemporary clinical practice,
      particularly in patients with DM. METHODS: In the multicenter randomized DARE
      trial, patients with BMS or DES ISR were randomized in a 1:1 fashion to treatment
      with a PEB or an EES. Patients underwent angiographic follow-up after 6 months.
      For the purpose of this analysis, the relative performance of PEB versus EES in
      diabetic patients was investigated. RESULTS: Of 278 patients enrolled in DARE, 88
      (32%) had DM, of whom 46 were randomized to EES and 42 to PEB treatment. Of
      patients with DM, 48 (55%) had DES-ISR. Angiographic follow-up was available in
      30 patients (72%) in the PEB group and 36 patients (78%) in the DES group. There
      were no differences in terms of 6-months minimal lumen diameter in diabetic
      patients treated with EES (1.46 +/- 0.66 mm) versus PEB (1.78 +/- 0.58 mm, P =
      0.15). Adverse events at one year follow-up were similar in both groups, with
      Major Adverse Events (MAE, death, target vessel MI, or TVR) occurring in 17.4% in
      the EES group versus 11.9% in the PEB group, P = 0.44. CONCLUSIONS: In patients
      with ISR and DM, use of a PEB resulted in similar 6-months in-segment minimal
      lumen diameter and comparable rates of MAE. In-segment late loss at 6 months was
      significantly lower in the PEB arm. Although larger trials in DM patients with
      ISR are necessary, PEB is a promising treatment option obviating the need for
      additional stent implantation.

PMID- 30232825
TI  - Principles and considerations for effective academia-industry collaboration in
      pharmacoepidemiology.

PMID- 30232826
TI  - Mechanism and Effect of Polar Styrenes on Scandium-Catalyzed Copolymerization
      with Ethylene.
AB  - Copolymerization of ethylene (E) and polar vinyl monomers remains a problem
      because E propagation is hindered. Herein, for the first time, we report the
      copolymerization of E and polar styrenes (SR ) by using an oxophilic scandium
      catalyst that exhibits higher turnover frequencies than both E and SR
      homopolymerizations when R is an electron-withdrawing group. This positive
      comonomer effect was elucidated through computing reaction profiles of E/SF
      copolymerization at the DFT (B3PW91) level of theory. It reveals that the
      secondary interaction between Sc3+ and phenyl of the last and penultimate
      inserted SF units leads to a decrease of the E insertion barrier, because the
      electron-withdrawing substituent enhances the electrophilicity of Sc3+ by an
      inductive effect mediated by the secondary interaction. After three consecutive
      insertions of the E units, the secondary interaction is lost and the SF insertion
      is kinetically preferred over the E insertion. This process is in line with the
      NMR spectrum analyses which show that the resultant copolymers mainly contain SR
      (E)x SR sequences where x<=3.

PMID- 30232827
TI  - Quantitative Proteomic Analysis Reveals Caffeine-Perturbed Proteomic Profiles in
      Normal Bladder Epithelial Cells.
AB  - Lower urinary tract symptoms (LUTSs) are highly prevalent among the elderly and
      negatively impact quality of life. Since caffeinated beverages are enjoyed
      worldwide and the relationship between LUTS and caffeine is still not fully
      understood, it would be of particular interest to examine the underlying
      mechanisms that drive caffeine's influence on LUTS development and progression.
      The aim of this study is to characterize the effects of caffeine on hTert
      immortalized normal bladder epithelial cells by investigating whether exposure to
      caffeine can cause potential changes in the bladder proteome and/or biological
      pathways. In labeled LC-MS/MS proteomic analysis, 57 proteins are found as being
      differentially expressed in caffeine-treated bladder epithelial cells, compared
      to controls; this included 32 upregulated and 25 downregulated proteins. Further
      functional gene enrichment analysis reveals that caffeine affects major
      biological pathways, including those for "muscle contraction" and "chromatin
      assembly." These findings provide new scientific insights that may be useful in
      future studies investigating the role of caffeine in bladder dysfunctions.

PMID- 30232828
TI  - 35th European Peptide Symposium 26th -31st August 2018 | Dublin City University,
      Ireland.

PMID- 30232829
TI  - Acute effects of salt on blood pressure are mediated by serum osmolality.
AB  - It is classically thought that it is the amount of salt that is critical for
      driving acute blood pressure responses. However, recent studies suggest that
      blood pressure responses, at least acutely, may relate to changes in serum
      osmolality. Here, we test the hypothesis that acute blood pressure responses to
      salt can be altered by concomitant water loading. Ten healthy patients free of
      any disease and medication underwent 4 interventions each a week apart in which
      they took 300 mL of lentil soup with no salt (visit 1), lentil soup with 3 g salt
      (visit 2), or lentil soup with 3 g salt and 500 mL water (visit 3) or 750 mL
      water (visit 4). At each visit, hourly blood measurements and blood pressure
      measurements (baseline, 1st, 2nd, 3rd, and 4th hour) were performed and plasma
      osmolarity, sodium and copeptin levels were measured. Patients receiving the 3 g
      salt showed a 6 mOsm/L change in osmolality with a 2.5 mmol/L change in plasma
      sodium and 10 mm Hg rise in systolic blood pressure at 2 hours. When the same
      patients drank salty soup with water, the changes in plasma osmolarity, plasma
      sodium, and blood pressure were prevented. The ability to raise blood pressure
      acutely with salt appears dependent on changes in plasma osmolality rather than
      the amount of salt. Our findings suggest that concurrent intake of water must be
      considered when evaluating the role of salt in blood pressure.

PMID- 30232830
TI  - Beware the masquerade: One patient, two mimics.

PMID- 30232831
TI  - Preparation of stoichiometric molecularly imprinted polymer coatings on magnetic
      particles for the selective extraction of auramine O from water.
AB  - A novel magnetic molecularly imprinted polymer for the selective recognition of
      auramine O was rationally designed via screening from a library of nonimprinted
      polymers. A stoichiometric ratio of functional monomer (itaconic acid) and
      template molecule (auramine O) was found to be 1.5. Meanwhile, the synthesized
      SiO2 @Fe3 O4 was modified by 0.5 mol/L hydrochloric acid to facilitate the
      preparation of magnetic molecularly imprinted polymer particles. Adsorption
      experiments showed that the magnetic polymer particles exhibited good
      selectivity, recoveries, and enrichment performance. The stoichiometric imprinted
      polymers have been employed for the selective preconcentration of auramine O from
      lake water sample. The high specificity of the stoichiometric imprinted polymers
      was proven in the extraction of mixture solution of auramine O, auramine O
      hydrochloride, and chrysoidine, and the recoveries ranged between 99.66 and
      108.75% (RSD 2.6-3.7%, n = 3) for lake water. These results suggest that this
      method is effective and can be successfully applied to the analysis of auramine O
      in environmental water samples.

PMID- 30232832
TI  - Comparative safety of NSAIDs for gastrointestinal events in Asia-Pacific
      populations: A multi-database, international cohort study.
AB  - PURPOSE: The safety of nonsteroidal anti-inflammatory drugs (NSAIDs) commonly
      used in Asia-Pacific countries has had limited study. We assessed the risk of
      hospitalization for gastrointestinal events with loxoprofen and mefenamic acid
      compared with other NSAIDs in Asia-Pacific populations. METHODS: We conducted a
      cohort study using a distributed network with a common data model in Australia,
      Hong Kong, Japan, Korea, and Taiwan. We included patients who initiated
      diclofenac, loxoprofen, mefenamic acid, or celecoxib and followed them until
      their first gastrointestinal hospitalization, switch or discontinuation of
      medication, disenrollment, or end of database coverage. We used Cox proportional
      hazards models to assess hospitalization risk. RESULTS: We identified 9879
      patients in Japan, 70 492 in Taiwan, 263 741 in Korea, and 246 in Hong Kong who
      initiated an NSAID, and 44 013 patients in Australia, a predominantly Caucasian
      population. The incidence of gastrointestinal hospitalization was 25.6 per 1000
      person-years in Japan, 32.8 in Taiwan, 11.5 in Korea, 484.5 in Hong Kong, and
      35.6 in Australia. Compared with diclofenac, the risk of gastrointestinal events
      with loxoprofen was significantly lower in Korea (hazards ratio, 0.37; 95% CI,
      0.25-0.54) but not in Japan (1.65; 95% CI, 0.47-5.78). The risk of
      gastrointestinal events with mefenamic acid was significantly lower in Taiwan
      (0.45; 95% CI, 0.26-0.78) and Korea (0.11; 95% CI, 0.05-0.27) but not Hong Kong
      (2.16; 95% CI, 0.28-16.87), compared with diclofenac. CONCLUSIONS: Compared with
      diclofenac, loxoprofen was associated with a lower risk of gastrointestinal
      hospitalizations in Korea and mefenamic acid with a lower risk in Taiwan and
      Korea.

PMID- 30232833
TI  - Diastereo- and Enantioselective Propargylation of 5H-Thiazol-4-ones and 5H-Oxazol
      4-ones as Enabled by Cu/Zn and Cu/Ti Catalysis.
AB  - Reported is the asymmetric propargylic substitution (APS) reaction of 5H-thiazol
      4-ones using a Cu/Zn dual metal catalytic system and the APS reaction of 5H
      oxazol-4-ones using a Cu/Ti catalytic system. These reactions furnish functional
      group-rich, terminal-alkyne-containing products with two vicinal stereocenters in
      high yields and with good to excellent diastereo- and enantioselectivities. This
      study demonstrates the use of dual metal catalytic systems as a viable approach
      to improve the selectivity profiles of the copper-catalyzed APS reactions.

PMID- 30232835
TI  - Aligning ambulance dispatch priority to patient acuity: A methodology.
AB  - OBJECTIVE: In Victoria, Australia, Emergency Medical Service (EMS) demand has
      increased almost 5% per annum over the past 5 years. This may adversely affect
      response times to time-critical patients. Additionally, >55% of cases have
      received Code 1 (lights/sirens) responses. Primary telephone triage occurs using
      the Medical Priority Dispatch System (MPDS); however, MPDS is reported to be
      highly sensitive, with common over-triage. The present study describes the
      methodology applied to better align the response allocated to MPDS determinant
      codes with patient acuity. METHODS: Data between October 2013 and August 2014
      were extracted from the Ambulance Victoria data warehouse. The decision to
      allocate MPDS determinant codes to a lower response priority and/or secondary
      triage was based on epidemiological profiling and, in some cases, expert panel
      review. RESULTS: The review identified 105 MPDS codes receiving a Code 1 response
      as suitable for a Code 2 (urgent) response, and 221 Code 1 or 2 codes as suitable
      for secondary triage. Data analysis estimated a reduction in Code 1 responses by
      28%, and an increase in the secondary triage caseload by 120%. Modelling also
      predicted a 2.6 percentage point improvement in the proportion of Code 1 cases
      attended within 15 min. CONCLUSION: Analysis of a large EMS dataset supported
      changes to the EMS response priority for a number of MPDS determinant codes. Such
      changes should improve the alignment between EMS response and patient acuity, and
      improve response times to time-critical patients. Other EMS with electronic data
      could consider testing this methodology.

PMID- 30232834
TI  - Exercise therapy of patients with irritable bowel syndrome: A systematic review
      of randomized controlled trials.
AB  - BACKGROUND: As drug use has limitations in the treatment of irritable bowel
      syndrome (IBS), increasing attention is being paid to nondrug therapies and
      complementary treatments, especially exercise. It is known that bowel movements
      are more frequent and colon transit is more rapid in physically active
      individuals than in sedentary individuals. However, the effects of exercise on
      IBS are unclear. PURPOSE: We conducted a systematic review to assess the effects
      of exercise on IBS. METHODS: We searched PubMed, Web of Science, EMBASE, Cochrane
      Library, and two Chinese databases (Wanfang Database and Chinese Biomedical
      Literature [CBM]) for eligible studies. We extracted and pooled relevant
      information regarding the effects of exercise in patients with IBS. The primary
      outcomes were gastrointestinal symptoms, quality of life, depression, and
      anxiety. KEY RESULTS: A total of 683 patients with IBS from 14 randomized
      controlled trials met our inclusion criteria. The exercise interventions in this
      review were yoga, walking/aerobic physical activity, Tai Ji, mountaineering, and
      Baduanjin qigong activity. The results of this review suggested exercise had
      significant benefits for patients with IBS, but studies were limited by the
      strong risk of bias. CONCLUSIONS AND INFERENCES: Our findings suggest that
      exercise is potentially a feasible and effective treatment for IBS patients.
      However, because of methodologic issues, no firm conclusions could be drawn about
      the true effects of this intervention. Researchers should design a rigorous study
      to assess the effects of exercise on IBS.

PMID- 30232836
TI  - First assessment of interferon gamma release assay results among healthcare
      workers at a general hospital in China.
AB  - INTRODUCTION: China has a very high tuberculosis (TB) burden. The interferon
      gamma release assay (IGRA) is more specific for the diagnosis of latent
      tuberculosis infection (LTBI) than the tuberculin skin test, especially among
      populations with a high degree of coverage by the BCG vaccine. OBJECTIVES: To
      evaluate the first screening of healthcare workers (HCW) for LTBI using the IGRA
      at a general hospital in Beijing. METHODS: A pilot screening program for LTBI was
      triggered by accidental contact between HCW and two patients with active TB in
      the emergency department (ED). Given the necessity of estimating the overall LTBI
      prevalence in the institution, a sample of 518 HCW was enrolled in our cross
      sectional study. The second IGRA was repeated with 43 of the 121 HCW in the ED
      after exposure to index TB cases. Data on putative risk factors were collected
      with a self-administered questionnaire. RESULTS: The prevalence of LTBI in the
      targeted population was 21.8%. Differences in the prevalence of LTBI were
      significantly related to age, employment duration, and history of occupational
      exposure. A lack of childhood BCG vaccination was independently associated with
      the prevalence of LTBI (adjusted OR: 1.686, 95% CI: 1.045-2.723, P = .0325). No
      new LTBI was diagnosed 12 weeks postexposure. No HCW adopted the preventive
      treatment for LTBI. CONCLUSIONS: Considering the high morbidity of LTBI among HCW
      even in general hospitals, it is essential to formulate government policies and
      institutional operation protocols for the systematic screening, registration, and
      administration of prophylaxes for the control of LTBI.

PMID- 30232837
TI  - Relationship between water and salt intake, osmolality, vasopressin, and
      aldosterone in the regulation of blood pressure.

PMID- 30232838
TI  - Hybrid-stenting with metallic and bioresorbable drug-eluting stents 2-year
      clinical outcomes in KUM ABSORB registry.
AB  - AIM AND OBJECTIVE: We sought to investigate and compare outcomes 2 years after
      Hybrid-stenting with bioresorbable vascular scaffolds (BVS) and contemporary
      metallic drug-eluting stents (DES) within the same coronary lesion versus BVS
      alone. METHODS: Between 11/2012 and 7/2015 at our institution, 134 (33.2%) were
      treated with Hybrid-stenting for complex or long coronary lesions, 270 patients
      were treated by BVS alone. The primary outcome of interest was target lesion
      failure (TLF) at 2-years of follow-up. RESULTS: Patients treated by Hybrid
      stenting were more frequently men (80% vs. 70%, p = 0.04) had extensive
      multivessel disease (84% vs. 71%, p < 0.01) including more complex (89% vs. 52%,
      p < 0.01) and longer lesions (28.9 mm vs 16.4 +/- mm, p < 0.01) resulting in
      longer treated segments (47.3 mm vs 21.5 mm, p < 0.01) and more residual in
      segment stenosis (12.3% vs 8.5%, p < 0.01) compared to BVS alone patients. At 2
      years, cumulative incidence of TLF was 9.7% of Hybrid-stenting patients and 11.5%
      of BVS alone patients (p = 0.62), myocardial infarction (3.0% vs 4.1%, p = 0.59)
      and mortality (1.5% vs 4.1%, p = 0.17), respectively. Target lesion
      revascularization occurred in 9 Hybrid-stenting patients (2 located in DES) and
      in 20 BVS alone patients, cumulative incidence 6.7% vs. 7.4% (p = 0.80). Chronic
      kidney disease and residual in-segment stenosis >30% were identified as
      independent predictors of TLF at 2-years. CONCLUSION: Despite differences in
      clinical and angiographic profile, Hybrid-stenting performed similar to BVS alone
      at 2 years after percutaneous coronary intervention.

PMID- 30232839
TI  - Rapid isolation and characterization of crocins, picrocrocin, and crocetin from
      saffron using centrifugal partition chromatography and LC-MS.
AB  - This study demonstrates a simple method for one-step isolation of the main
      secondary metabolites of a hydroalcoholic extract of Crocus sativus stigmas
      (saffron) using step-gradient centrifugal partition chromatography. The analysis
      was performed in dual and elution-extrusion mode, using five biphasic systems of
      the solvents heptane/ethyl acetate/butanol/ethanol/water in ratios of
      4:10:0:4:10, 1:13:0:4:10, 1:12:1:4:10, 1:10:3:4:10, and 1:7:6:4:10. Five major
      crocins, picrocrocin, and crocetin were directly isolated in one step. Scaling up
      to preparative level, allowed the recovery of significantly high quantities of
      pure compounds, especially trans-crocin-4, saffron's principal crocin. Comparing
      dual-mode and elution-extrusion, in dual-mode, the trans-crocin-4 containing
      fractions were co-eluted with a high amount of free beta-d-glucose. In contrast,
      absence of free beta-d-glucose was observed in the corresponding trans-crocin-4
      fractions obtained by the second method denoting its superiority against dual
      mode. Initiating analysis with the 4th solvent-system afforded selective
      isolation of trans-crocin-4, with reduction in experimental time and solvent
      consumption. Structure elucidation was performed by nuclear magnetic resonance
      spectroscopy, liquid chromatography with mass spectrometry, and high-resolution
      tandem mass spectrometry. The proposed methodology comprises an integrated
      approach for the purification and characterization of biologically active saffron
      components in a fast, selective, and environmentally friendly manner.

PMID- 30232840
TI  - sigma-Aromaticity in a Fully Unsaturated Ring.
AB  - Aromaticity is one of the most fundamental and fascinating chemical topics,
      attracting both experimental and theoretical chemists owing to its many
      manifestations. Both sigma- and pi-aromaticity can be classified depending on the
      character of the cyclic electron delocalization. In general, sigma-aromaticity
      stabilizes fully saturated rings with sigma-electron delocalization whereas the
      traditional pi-aromaticity describes the pi-conjugation in fully unsaturated
      rings. Here, we demonstrate a strong correlation between nucleus-independent
      chemical shift (NICS) values and extra cyclic resonance energies (ECREs), which
      are used to evaluate the sigma-aromaticity in an unsaturated three-membered ring
      (3MR) of cyclopropene, which were computed by molecular orbital (MO) theory and
      valence bond (VB) theory, respectively. Further study shows that the fully
      unsaturated ring in methylenecyclopropene and its metallic analogy is sigma
      aromatic. Our findings revolutionize the fundamental knowledge of the concept of
      sigma-aromaticity, thus opening an avenue to design sigma-aromaticity in other
      fully unsaturated systems, which are traditionally reserved as the domain of pi
      aromaticity.

PMID- 30232841
TI  - Effect of funding source on reporting bias in studies of intravitreal anti
      vascular endothelial growth factor therapy for retinal vein occlusion.
AB  - PURPOSE: To examine the relationship between industry funding and outcome
      reporting bias in high-quality studies investigating the use of intravitreal anti
      vascular endothelial growth factor (VEGF) agents for patients with macular oedema
      secondary to branch or central retinal vein occlusion (RVO). METHODS: This
      systematic review in PubMed and Ovid MEDLINE examined all randomized clinical
      trials and meta-analyses published in journals with impact factor of >=2 that
      investigated effectiveness of intravitreal anti-VEGF therapy in patients with
      RVO. The main outcome measure was correspondence between statistical outcome and
      abstract conclusion wording. RESULTS: Forty-five studies met inclusion criteria;
      38 (84%) showed correspondence between outcome and abstract conclusion without
      difference between industry-funded and nonindustry-funded publications (p = 0.39)
      or between publications in journals with impact factor >=3 versus <3 (p = 0.96).
      CONCLUSION: In high-quality studies of intravitreal anti-VEGF therapy for RVO,
      neither industry funding nor journal impact factor affected the rate of outcome
      reporting bias.

PMID- 30232842
TI  - An Intriguing Pea-Like Nanostructure of Cobalt Phosphide on Molybdenum Carbide
      Incorporated Nitrogen-Doped Carbon Nanosheets for Efficient Electrochemical Water
      Splitting.
AB  - The development of noble-metal-free, efficient, electrochemical, water-splitting
      catalyst systems has attracted considerable attention in recent times. In this
      study, a metal-organic framework based synthetic route to couple two non-noble
      metal-based catalysts, CoP and Mo2 C, supported on nitrogen-doped carbon has been
      developed. The strategy enables the formation of a nanohybrid with an attractive
      pea-like morphology, in which spherical CoP particles (~10 nm) are embedded on
      two-dimensional nitrogen-doped carbon enriched with ultrafine Mo2 C
      nanoparticles. This composition boosts the electrochemical alkaline water
      splitting reaction by showing overpotentials (eta10 ) of only 94 and 265 mV for
      the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER),
      respectively, at a current density of 10 mA cm-2 . Additionally, in an acidic
      medium, the eta10 values are 107 and 330 mV for HER and OER, respectively; this
      suggests good bifunctionality at both lower and higher pH levels. Overall water
      splitting has been demonstrated by the developed catalyst at a cell voltage of
      1.64 V for a current density of 10 mA cm-2 in alkaline medium, and a constant
      current is produced for more than 40 h under chronoamperometric conditions. This
      study describes the combination of two nanocomponents, with interconnected
      surface structures, which result in highly active and stable electrocatalytic
      performance.

PMID- 30232843
TI  - Chemoselective Hydrogenation of Cinnamaldehyde on Iron-Oxide Modified Pt/MoO3-y
      Catalysts.
AB  - Hydrogenation of alpha,beta-unsaturated aldehydes to unsaturated alcohols suffers
      a huge challenge in chemoselectivity. Herein, surface decoration by FeOx is
      introduced to remarkably improve the selectivity of cinnamyl alcohol (COL) in
      cinnamaldehyde (CAL) hydrogenation on Pt/MoO3-y . The enhanced acidity on Pt-FeOx
      interfaces is beneficial for the chemisorption and activation of C=O bonds,
      promoting selective hydrogenation. The optimal catalysts with defined FeOx
      decoration afford efficient and chemoselective CAL hydrogenation (91.3 %
      selectivity) under mild conditions (PH2 =1 MPa, T=30  degrees C). Moreover, such
      innovation is further extended to develop other efficient metal (Ir, Rh and Pd)
      catalysts, identifying a universal promotion to Pt-group metals. This work is
      anticipated to inspire the rational design of high-performance catalysts via
      effective surface/interface engineering.

PMID- 30232845
TI  - Validation of optical properties quantification with a dual-step technique for
      biological tissue analysis.
AB  - To approach wide-field optical properties quantification in real heterogeneous
      biological tissue, we developed a Dual-Step setup that couples a punctual diffuse
      reflectance spectroscopy (DRS) technique with multispectral imaging (MSI). The
      setup achieves wide-field optical properties assessment through an initial
      estimation of scattering with DRS, which is used to estimate absorption with MSI.
      The absolute quantification of optical properties is based on the ACA-Pro
      algorithm that has been adapted both for DRS and for MSI. This paper validates
      the Dual-Step system not only on homogeneous Intralipid phantoms but also on a
      heterogeneous gelatine phantom with different scattering and absorbing
      properties.

PMID- 30232846
TI  - [Acupuncture Analgesia-Panorama Multi-dimensional Treatment of Pain].
AB  - Along with advances in pain medicine, people have a deep understanding about
      pain. It is now considered that pain is a complex activity of the nerve system,
      particularly the high nerve centers, and is composed of sensory, affective,
      cognitive, and social interaction. By the help of new techniques and instruments
      of brain science, the neural circuits involved in pain generation have been
      understood intensively, partially explaining why pain is composed of multiple
      components and how the sensation, emotion and cognition of pain are influenced
      each other. Acupuncture analgesia is widely used in clinical treatment and has a
      definite therapeutic effect. Along with the revision of definition of pain, the
      research of acupuncture analgesia needs to accommodate the so-called multiple
      dimensions and their interactions, will effectively deepen its connotation and
      denotation, and expand its application range, opening up a wider clinical
      prospect.

PMID- 30232844
TI  - Molecular evolution of elements controlling HLA-C expression: Adaptation to a
      role as a killer-cell immunoglobulin-like receptor ligand regulating natural
      killer cell function.
AB  - The regulatory elements controlling the transcription of the HLA-A, HLA-B, and
      HLA-C genes have been extensively studied and compared. However, few studies have
      considered regulatory differences in the HLA genes from the perspective of their
      role as ligands for the killer-cell immunoglobulin-like receptor (KIR) family of
      HLA receptors expressed by natural killer (NK) cells. HLA-C is the most recently
      evolved gene, and there is considerable evidence pointing to its emergence as a
      specialized KIR ligand playing a major role in the missing-self recognition
      system of NK cells. Here I evaluate gene-specific differences in regulatory
      elements of the HLA genes, showing alterations that are consistent with the
      adaptation of HLA-C to a role in NK cell regulation.

PMID- 30232847
TI  - [Mechanisms of Acupuncture for Inflammatory Pain].
AB  - Although acupuncture, especially electroacupuncture (EA) is widely used to treat
      pain, its mechanisms have not been completely understood. In the present paper,
      we review the development of researches on the underlying mechanisms of EA in
      relieving inflammatory pain in recent years from a)peripheral inflammation
      mediated immune response and neuro-immune interaction of receptors on primary
      nociceptors, b) crosstalk of neurotransmitters or neuromodulators, cellular
      signaling pathways, other related bioactive molecules, as well as glial
      activation in the dorsal horns of spinal cord, and c) supraspinal modulation of
      both sensory and affective components of pain. Inflammatory pain involves complex
      neuro-immune networks of neurons and non-neurons, various inflammatory mediators,
      neurotransmitters, neuromodulators and cellular signaling molecules in the
      peripheral and central nervous systems. Therefore, the analgesic mechanism of
      acupuncture still needs to be studied in depth at multi-levels and multi-targets,
      for instance, the reciprocal actions of peripheral opioid peptide, adenosine and
      TRPV 1 (which have been demonstrated to be involved in EA analgesia
      individually), the roles of spinal cord adenosine A 1 receptor (A 1 R) and A 2 R
      (for which fewer studies have been conducted), the interactions of classical
      neurotransmitters/neuromodulators/neuropeptides and their receptors, changes of
      intracellular molecules at transcriptional and translation levels, etc. during
      acupuncture analgesia. Furthermore, the mechanisms underlying reciprocal actions
      of neurotransmitters, neuromodulators and their receptors complicated in
      acupuncture-induced relief of pain affection in the higher brain regions also
      need to be explored further.

PMID- 30232848
TI  - [Feasibility of Joint Application of Techniques of Optogenetics and
      Neuroelectrophysiology to Research of Acupuncture Analgesia].
AB  - Since the invention of optogenetic technology, it has greatly promoted the
      development of neuroscience. Currently, optogenetic approaches have been mostly
      used to map neural circuits and new neuropharmacology but are rarely seen in the
      research field of acupuncture analgesia. The mechanism of neural circuits
      contributing to acupuncture analgesia, an important research hotspot in recent
      years, has not been fully determined. The optogenetic techniques can be used to
      modulate and control specific cells, provides highly precise spatial and temporal
      resolution, is repeatable, and may functionally dissect neuronal networks in
      vivo. The neuronal activities and their information transmission, processing and
      storage in intercluster neural networks in different brain regions, and the
      correlation between behavioral changes and electrical activities of neurons in
      vivo studies are mainly captured by the implanted microelectropode array, etc. If
      these two (or more) approaches are combined together, it is definitely and highly
      helpful to reveal the driving dynamics of neural circuits, plasticity and
      temporal-spatial activity mode of neurons, as well as behavioral reactions of
      animals with chronic pain during acupuncture analgesia and may open a new
      prospect for the application of acupuncture analgesia study.

PMID- 30232849
TI  - [Electroacupuncture Relieves Pain by Down-regulating Expression of Hippocampal
      High Mobility Group Protein 1 and Contents of TNF-alpha and IL-1 beta in Rats
      with Chronic Neuropathic Pain].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of high
      mobility group protein 1 (HMGB 1) and related downstream effectors of
      proinflammatory cytokines in the hippocampus in chronic neuropathic pain rats, so
      as to investigate its mechanism underlying neuropathic pain relief. METHODS: Male
      SD rats were randomized into sham, model, and EA groups, with 12 rats in each
      group. The neuropathic pain model was established by ligature of the left sciatic
      nerve to induce chronic constriction injury (CCI). EA was applied to bilateral
      "Zusanli"(ST 36) and "Yanglingquan"(GB 34) for 30 min, once daily for 7 days. The
      mechanical withdrawal threshold (WMT) was detected using an electronic von Frey
      anesthesiometer. The expression level of HMGB 1 in the hippocampus was determined
      using quantitative RT-PCR and Western blot, separately, and the contents of
      hippocampal TNF-alpha and IL-1 beta were detected by ELISA. RESULTS: Compared
      with the sham group, the MWT values were markedly decreased on day 7, 10 and 14
      after modeling in the model group (P<0.001). On day 10 and 14 after modeling, the
      MWT values were significantly up-regulated in the EA group relevant to those of
      the model group (P<0.05, P<0.01). The expression levels of HMGB1 mRNA and
      protein, and the contents of hippocampal TNF-alpha and IL-1 beta were markedly
      increased in the model group relevant to the sham group (P<0.001), and
      significantly down-regulated in the EA group relevant to the model group
      (P<0.001, P<0.01, P<0.05). CONCLUSION: EA stimulation of ST 36-GB 34 can relieve
      pain in chronic neuropathic pain rats, which may be related to its actions in
      down-regulating the levels of HMGB 1 and its downstream proinflammatory cytokines
      TNF-alpha and IL-1 beta in the hippocampus.

PMID- 30232850
TI  - [Electroacupuncture Relieves Visceral Hypersensitivity by Down-regulating Mast
      Cell Number,PAR-2/TRPV 1 Signaling, etc. in Colonic Tissue of Rats with Irritable
      Bowel Syndrome].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Shangjuxu" (ST 37, Lower Confluent point) and "Tianshu" (ST 25, Front-Mu point)
      on visceral pain and expression of colonic tryptase(Try), proteinase-activated
      receptor 2(PAR-2),transient receptor potential channel vanilloid subfamily member
      1 (TPRV 1),substance P (SP) and calcitonin gene-related peptide (CGRP) in rats
      with irritable bowel syndrome (IBS), so as to explore its mechanisms underlying
      improvement of IBS. METHODS: Forty male Sprague Dawley rats were equally
      randomized into normal control (control), model, medication and EA groups (n=10
      in each). The IBS model was established by chronic acute combining stress (CACS,
      water deprivation, fasting, tail clamping, forced swimming in ice water,
      restraint, etc.) for 21 days. Rats of the medication group were treated by gavage
      of Pinaverium Bromide (1 mg/mL, 15 mg/kg), once daily for 14 d. EA (10 Hz/50 Hz,
      0.2-0.3 mA) was applied to bilateral ST 37 and ST 25 for 30 min, once daily for
      14 d. The muscular withdrawal reflex (AWR) of both abdomen and buttock was
      detected by colorectal distension (CRD) with a water-filled balloon for examining
      the visceral hypersensitivity. The number of mast cells in the colonic tissue was
      counted after toluidine blue stain. The immunoactivity of colonic Try was
      determined by immunochemistry and the expression of colonic PAR-2, TRVP 1, SP and
      CGRP proteins detected by Western blot. RESULTS: After modeling, the body weight
      was significantly decreased in IBS rats of the model, medication and EA groups
      compared with their own individual pre-treatment and with the control group
      (P<0.01), and markedly higher in both medication and EA groups than in the model
      group (P<0.05, P<0.01). The intra-colonic volume thresholds for inducing
      abdominal and hip AWR were significantly lower in the model group than in the
      normal control group (P<0.01), and obviously higher in both medication and EA
      groups than in the model group (P<0.05,P<0.01). The AWR scores of intra
      colorectal balloon at volumes of 0.5, 1.0 and 1.5 mL of water were significantly
      higher in the model group than in the control group (P<0.01), and considerably
      lower in the EA and medication groups than in the model group (P<0.01). The
      number of colonic MC and the expression levels of colonic Try, PAR-2, TRPV 1, SP
      and CGRP proteins were significantly higher in the model group than in the
      control group (P<0.01), and obviously decreased in both medication and EA groups
      relevant to the model group (P<0.01). Comparison between the medication and EA
      groups showed that the decreased expression levels of colonic PAR-2, TRPV 1, SP
      and CGRP proteins were significantly lower in the EA group than in the medication
      group (P<0.05), but no significant differences were found between the two groups
      in intra-colonic volumes for inducing AWR, AWR scores, body weight, and colonic
      MC number and Try immunoactivity levels (P>0.05).. CONCLUSION: EA of ST 37 and ST
      25 can relieve visceral hypersensitivity in IBS rats, which may be associated
      with its effects in down-regulating the number of MC and the expression of PAR-2,
      TRVP 1, SP, CGRP and Try proteins in the colonic tissue.

PMID- 30232851
TI  - [Shallow Fire-needle Acupuncture Stimulation Plus Cupping Relieves Neuralgia and
      Down-regulates Serum Substance P Level in Patients with Acute Herpes Zoster].
AB  - OBJECTIVE: To observe the influence of repeated shallow fire-needle acupuncture
      stimulation plus cupping on local neuralgia and serum substance P(SP)content in
      patients with acute herpes zoster (AHZ). METHODS: A total of 60 cases of AHZ
      patients were randomly divided into control (medication) group and treatment
      (medication plus fire-needle) group (n=30 in each). Patients of both groups were
      ordered to take Famciclovir (0.25 g/time, three times a day) and Mecobalamin (0.5
      g/time, three times a day) orally for 7 days. In addition, patients of the
      treatment group were also treated by repeated shallow fire-needle stimulation and
      cupping, once a day for 7 days. Before and after the treatment, the patient's
      pain severity was assessed using visual analogue scale (VAS) and serum SP
      concentration was measured using ELISA. RESULTS: After the treatment, the VAS
      scores and serum SP concentrations in both groups were significantly decreased in
      comparison with those of their own pre-treatment (P<0.01), and were significantly
      lower in the treatment group than in the control group(P<0.01). There was a
      highly positive correlation between the decreased VAS score and serum SP content
      in the treatment group(P<0.01). CONCLUSION: Repeated shallow fire-needle
      stimulation plus cupping can accelerate the relief of local neuralgia in AHZ
      patients, which may be associated with its effect in down-regulating serum SP
      level.

PMID- 30232852
TI  - [Electroacupuncture Relieves Obesity by Up-regulating PGC-1 alpha/UCP-1 Signaling
      in White Adipose Tissue in Diet-induced Obesity Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the activities of
      peroxisome proliferator-activated receptor gamma coactivator-1 alpha/uncoupling
      protein-1 (PGC-1 alpha/UCP-1) signaling pathway in white adipose tissue(WAT)of
      diet-induced obesity (DIO) rats, so as to reveal its underlying mechanism in body
      weight loss. METHODS: Thirty-four male Wistar rats were randomly divided into
      normal diet (control, n=10), high fat diet (model), sham EA-acupoint and EA
      groups (n=8 in each of the latter 3 groups). The obesity model was established by
      feeding the rats with high fat diet containing lard oil, sugar, albumen powder,
      cholesterol, salt and sodium cholate for 12 weeks. EA (2 Hz/15 Hz, 1 mA) was
      applied to bilateral "Zusanli" (ST 36) and "Tianshu" (ST 25) or sham acupoints
      (about 5 mm beside ST 36 and ST 25) for 30 min, once daily, 5 times per week for
      a total of 8 weeks. During the treatment, all rats were fed with normal diet, and
      their body weight and length were measured once a week for calculating the Lee's
      index. The contents of serum total cholesterol (TC) and triglyceride (TG) were
      measured by using biochemical methods. The immunoactivity of PGC-1 alpha and UCP
      1 in the abdominal WAT was detected by immunohistochemistry. RESULTS: After
      modeling, the Lee's index, serum TC and TG contents were significantly increased,
      and the levels of serum HDL-C, and PGC-1 alpha and UCP-1 immunoactivity in WAT
      considerably decreased in the model group relevant to the control group (P<0.05).
      Following the treatment, the Lee's index, TC and TG contents were significantly
      down-regulated while HDL-C and PGC-1 alpha and UCP-1 immunoactivity were
      obviously up-regulated in the EA-acupoint group relevant to the model group
      (P<0.05). CONCLUSION: EA can effectively reduce the body weight and adipose
      content in obesity rats, which may be closely related to its effect in up
      regulating PGC-1 alpha/UCP-1 signaling in WAT, suggesting an efficacy of EA in
      promoting the browning of WAT.

PMID- 30232853
TI  - [Fire-needle Acupuncture Intervention Relieves Ankle-joint Inflammatory Reactions
      Possibly by Down-regulating Serum TNF-alpha and Anti-cyclic Citrullinated Peptide
      Antibody Levels in Collagen-induced Arthritis Rats].
AB  - OBJECTIVE: To observe the effect of fire-needle acupuncture of "Zusanli" (ST 36)
      and "Kunlun" (BL 60) on ankle-joint swelling and serum tumor necrosis factor
      alpha (TNF-alpha) and anti-cyclic citrullinated peptide antibody (ACPA) contents
      in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying
      improvement of rheumatoid arthritis (RA).. METHODS: Thirty-two male Wistar rats
      were randomized into control, model, medication (Methotrexate) and fire-needling
      groups (n=8 in each). The RA model was established by injecting type II chicken
      collagen (0.1 mol/L) plus Freund's complete adjuvant (primary immunization) and
      Freund's incomplete adjuvant (immunization once more) into the subcutaneous
      tissues of the right foot bottom, back and tail root of rats. Fire-needling was
      applied to the left and right "Zusanli" (ST 36) and "Kunlun" (BL 60)
      alternatively for 3 times in each acupoint, once daily for 10 days. For rats of
      the medication group, Methotrexate sodium chloride solution (0.1 mg/100 g) was
      administrated by gavage, once every 5 days, twice together. The rats' right hind
      ankle diameter was measured before and after the treatment. The X-ray film of the
      right ankle was taken, and the contents of serum TNF-alpha and ACPA were assayed
      by ELISA. RESULTS: The ankle diameter and serum concentrations of TNF-alpha and
      ACPA were significantly increased in the model group compared to the control
      group (P<0.05), and X-ray film showed swollen and deformed tarsus joints, and
      narrowing of the joint space. After the intervention, the ankle diameter, serum
      TNF-alpha and ACPA levels were considerably decreased in both medication and fire
      needle groups compared with the model group (P<0.05). Meanwhile, the joint
      swelling and bone deformity became relatively milder. There were no significant
      differences between the medication and fire-needling groups in the ankle diameter
      and the contents of serum TNF-alpha and ACPA (P>0.05). CONCLUSION: Fire-needling
      stimulation of ST 36 and BL 60, similar to Methotrexate, can relieve the
      inflammatory reactions of hind-ankle joint in CIA rats, which may be related to
      its effect in down-regulating ACPA and TNF-alpha levels.

PMID- 30232854
TI  - [Acupuncture Treatment Reduces Body Weight Possibly by Down-regulating Insulin
      and Leptin Resistance, and Up-regulating Soluble Leptin Receptor Level in
      Prediabetic Patients].
AB  - OBJECTIVE: To observe the effect of acupuncture of Feishu (BL 13), Pishu (BL 20),
      etc. on body weight, blood lipid, leptin (LP) and soluble leptin receptor (sOB-R)
      levels in prediabetic patients, so as to explore its mechanisms underlying
      treatment and prevention of prediabetes. METHODS: A total of 100 prediabetic
      patients were randomly assigned to medication (Metformin) group (n=35),
      acupuncture group (n=35) and simple lifestyle intervention group (n=30) with
      random number table method. All the patients of the 3 groups were treated with
      lifestyle intervention (reasonable diet and moderate physical exercise) and
      ordered to stop administration of any hypoglycemic drugs during the treatment
      period. Bilateral Feishu (BL 13), Pishu (BL 20), Weishu (BL 21), Shenshu (BL 23),
      Zusanli (ST 36) and Sanyinjiao (SP 6) were punctured with filiform needles which
      were manipulated by lifting, thrusting and twirling repeatedly for about 2 min
      every 5 min during 30 minutes' needle retaining. The acupuncture treatment was
      conducted once every other day for 12 weeks. Patients of the medication group
      were ordered to orally take Metformin tablets (0.5 g/time, twice a day) for
      continuous 12 weeks. Body mass index (BMI), waist circumference (WC), waist-to
      hip ratio (WHR), 2 h-postprandial blood glucose (2 h-PBG), fasting blood glucose
      (FBG), glycosyla-ted hemoglobin (HbA1c), total cholesterol (TC), triglyceride
      (TG), fasting insulin (FINS), serum LP and sOB-R levels were measured before and
      after the treatment. RESULTS: After the treatment, the BMI in the acupuncture
      group, and BMI, WC and WHR in the medication group were significantly decreased
      relevant to their own pre-treatment in each group (P<0.05, P<0.01). Following the
      treatment, the levels of FBG, 2 h-PBG, HbA1C, TC, TG, FINS, HOMA-IR and LP in
      both acupuncture and medication groups, and FBG in the simple lifestyle
      intervention group were significantly decreased in comparison with their own pre
      treatment in each group (P<0.01, P<0.05), and the levels of FBG, 2 h-PBG, HbA1C,
      TC and TG, HOMA-IR and LP in both acupuncture and medication groups were all
      considerably lower than those of the simple lifestyle intervention group
      (P<0.01,P<0.05). The level of FINS in the medication group was significantly
      lower than that of the simple lifestyle intervention group (P<0.05).
      Additionally, following the treatment, serum sOB-R contents in both acupuncture
      and medication groups were obviously increased compared with their own pre
      treatment in each group and also relevant to the simple lifestyle intervention
      group (P<0.01). No significant changes were found in the simple lifestyle
      intervention group in all the above-mentioned blood indexes except FBG (P>0.05).
      CONCLUSION: Acupuncture can induce body weight loss, down-regulate FINS, insulin
      resistance and LP resistance, and up-regulate sOB-R content in prediabetic
      patients, displaying a positive role in the treatment of prediabetes.

PMID- 30232855
TI  - [Warming Needle Moxibustion Relieves Symptoms of Lumbar Disc Herniation Patients
      and Upregulates Plasma beta-endorphin].
AB  - OBJECTIVE: To analyze the effect of warming needle moxibustion of Jiaji (EX-B 2),
      Huantiao (GB 30), etc. on lumbago and other symptoms of lumbar disc herniation
      (LDH) patients and changes of plasma beta-endorphin (beta-EP) content. METHODS: A
      total of 60 LDH patients were equally randomized into warming needle moxibustion
      group and conventional acupuncture group. Patients of the conventional
      acupuncture group were treated by puncturing lumbar Jiaji (EX-B 2), Huantiao (GB
      30), Weizhong (BL 40), and Yanglingquan (GB 34) with filiform acupuncture
      needles. Patients of the warming needle moxibustion group were treated by
      puncturing the same 4 acupoints, and with the acupuncture needle in lumbar EX-B 2
      attached an ignited moxa-stick segment. The treatment in both groups lasted for
      30 min every time, once every other day for 15 times, with 5 times being a
      therapeutic course and two days' rest between every two courses. The therapeutic
      effect was evaluated according to the "Criteria for Evaluating the Therapeutic
      Effect of Disorders of Traditional Chinese Medicine". The lumbago severity was
      assessed using visual analogue scale (VAS), and the lumbar functional activity
      assessed using modified Oswestry dysfunction (in objects-lifting, sitting,
      standing, walking, sleeping, pain, activity of daily living, social activity,
      outing, etc.) index (ODI). The plasma beta-EP content was assayed using ELISA.
      RESULTS: After the treatment, of the two 30 cases in the conventional acupuncture
      and warming needle moxibustion groups, 8 (26.67%) and 12 (40.00%) were under
      control, 8 (26.67%) and 10 (33.33%) had a marked improvement, 3 (10.00%) and 4
      (13.33%) were effective, and 11 (36.66%) and 4 (13.33%) ineffective, with the
      effective rates being 63.34% and 86.66%, respectively. The effective rate of the
      warming needle moxibustion was significantly higher than that of the conventional
      acupuncture (P<0.05). The VAS scores and ODI values of the two groups were
      gradually decreased along with the prolongation of treatment, and significantly
      lower in the warming needle moxibustion group than in the acupuncture group at
      the 1st, 2nd and 3rd course of treatment (P<0.01). The levels of plasma beta-EP
      were gradually increased in the two groups at the 1st, 2nd and 3rd course of
      treatment, and were obviously higher in the warming needle moxibustion group than
      in the conventional acupuncture group at each of the 3 courses (P<0.01). No
      obvious adverse reactions were observed in the two groups. CONCLUSION: Warming
      needle moxibustion has a better therapeutic effect in relieving lumbago and
      lumbar dysfunction, and can up-regulate blood beta-EP level.

PMID- 30232856
TI  - [Clinical Trial of Acupuncture Treatment of Gastroesophageal Reflux Disease
      Accompanied with Somnipathy at Acupoints of Governor Vessel at Back Segment].
AB  - OBJECTIVE: To observe the curative effect of needling stimulation of the back
      segment (10 spots below the spinous processes from T 3 to T 12)of the Governor
      Vessel in the treatment of gastroesophageal reflux disease(GERD)accompanied with
      somnipathy. METHODS: A total of 58 patients of GERD accompanied with somnipathy
      were randomly divided into acupuncture group (n=28) and medication group
      (n=30)according to random number table method. For patients of the acupuncture
      group, the spots below the spinous processes from T 3 to T 12, including
      acupoints Shenzhu (GV 12), Shendao (GV 11), Lingtai (GV 10), Zhiyang (GV 9),
      Jinsuo (GV 8), Zhongshu (GV 7) and non-acupoints (T 4, T 8, T 12) were punctured
      with filiform needles, once every other day for 8 weeks. Patients of the
      medication group were ordered to take Omeprazole capsules (20 mg/time), twice a
      day for 8 weeks. The therapeutic effect was assessed by "Reflux Diagnostic
      Questionnaire" (RDQ,scores of symptoms of heartburn, retrosternal pain, acid
      regurgitation and food regurgitation, 0-40 points), GERD symptom scale (scores of
      symptoms of the digestive system, five-sense organs, cardiovascular system, etc.,
      0-84 points) and Pittsburgh Sleep Quality Index (PSQI, scores of sleep quality,
      fall asleep time, sleep duration, sleep efficiency, etc., 0-21 points),
      respectively. RESULTS: After the treatment, RDQ score, GERD symptom scale score
      and PSQI score were significantly decreased in both acupuncture and medication
      groups compared with their own pre-treatment(P<0.01), and the decreased scores of
      RDQ, GERD scale and PSQI were significantly lower in the acupuncture group than
      in the medication group (P<0.01). The cured plus markedly effective rates for RDQ
      in the two groups were 43.3% (13/30) and 71.4% (20/28), respectively, and the
      effective rates of the medication and acupuncture groups were 56.7% (17/30) and
      89.3% (25/28) for GERD scale, and 60.0% (18/30) and 92.9% (26/28) for PSQI,
      respectively. The cured plus markedly effective rate for RDQ, and the effective
      rates for GERD scale and PSQI were signi-ficantly higher in the acupuncture group
      than in the medication group respectively (P<0.05,P<0.01).. CONCLUSION:
      Acupuncture stimulation of acupoints of Governor Vessel at the back segment is
      effective in improving symptoms of GERD patients with somnipathy.

PMID- 30232857
TI  - [Treatment of Simple Obesity Patients with Phlegm Dampness Stagnation Syndrome
      with Warming Needle Moxibustion].
AB  - OBJECTIVE: To observe the therapeutic effect of warming needle moxibustion
      stimulation of Hegu (LI 4), Tianshu (ST 25), Zhongwan (CV 12), Zusanli (ST 36),
      etc. for simple obesity patients with phlegm dampness stagnation syndrome
      (PDSS).. METHODS: A total of 60 simple obesity patients with PDSS were equally
      randomized into control group (13 men and 17 women, 18-53 years in age) and
      treatment group (14 men and 16 women, 19-45 years in age). All the patients of
      both groups were treated by diet control (trying their best to reduce high fat,
      high glucose and high salt foods, supplementing proteins). Patients of the
      treatment group received additional treatment of warming needle moxibustion,
      i.e., the inserted acupuncture needles in bilateral Hegu (LI 4), Tianshu (ST 25),
      Zhongwan (CV 12), and Zusanli (ST 36), Fenglong (ST 40), etc., were manipulated
      for a while with reducing technique after "deqi", followed by attachment of
      ignited moxa-cones at each of the needle handles for 30 min. The treatment was
      conducted once every other day for 8 weeks. The therapeutic effect was assessed
      according to the "Criteria for Diagnosis and Therapeutic Effect Evaluation of
      Simple Obesity" (1998). Before and after the treatment, body fat percentage (F%),
      body adiposity index (BAI), and body mass index (BMI) were calculated, serum
      triglyceride (TG), total cholesterol (CHO), low density lipoprotein cholesterol
      (LDL-C) and high density lipoprotein cholesterol (HDL-C) were detected using a
      biochemical analyzer. RESULTS: Following the treatment, of the two 30 cases of
      obesity patients in the control and treatment groups, 0 (0.0%) and 1 (3.3%) was
      under control, 11(36.7%) and 16 (53.3%) had a marked improvement, 8(26.7%) and 10
      (33.3%) were effective, and 11 (36.7%) and 3 (10.0%) failed in the treatment,
      with the effective rates being 63.3% and 90.0%, respectively. The effective rate
      of the warming needle moxibustion plus diet control was significantly superior to
      that of the simple diet control (P<0.01). After the treatment, the BMI, F%, serum
      CHO and TG levels and BAI in the treatment group were significantly decreased in
      comparison with its own pre-treatment in treatment group (P<0.05, P<0.01), while
      serum HDL-C of the treatment group was obviously increased compared with its own
      pre-treatment (P<0.01). The decreased F%, CHO and TG levels were markedly lower
      in the treatment group than in the control group (P<0.05,P<0.01).. CONCLUSION:
      Warming needle moxibustion has a positive effect for simple obesity patients with
      PDSS in controlling their symptoms.

PMID- 30232858
TI  - [Treatment of Vascular Cognitive Impairment by "Huayu Tongluo" Moxibustion].
AB  - OBJECTIVE: To observe the therapeutic effect of "Huayu Tongluo"(blood stasis
      removing and meridian-collateral-dredging) moxibustion for vascular cognitive
      impairment(VCI) patients and changes of insulin like growth factor -1(IGF-1)
      levels in serum after the treatment. METHODS: Sixty patients with VCI were
      randomly divided into medication (control) and moxibustion groups (n=30 in each
      group). Cotton cloth-separated moxibustion was applied to Baihui (GV 20) and
      Shenting (GV 24), and conventional moxibustion applied to Dazhui (GV 14) and
      Yongquan (KI 1) for 30 min, once daily, 6 times a week and for 30 days. Patients
      of the control group were treated by oral administration of Donepezil
      hydrochloride at the dose of 5 mg/night for 30 days. The core symptoms of
      traditional Chinese medicine (TCM), mini-mental state examination(MMSE), activity
      of daily living(ADL) and Montreal cognitive assessment(MoCA) scales were used to
      assess the therapeutic effect after the treatment. The content of serum IGF-1 was
      determined by ELISA. RESULTS: Of the two 30 cases in the control and moxibustion
      groups, 9 and 17 experienced marked improvement, 13 and were effective, 8 and 3
      ineffective, with the effective rates being 73.33% and 90.00%, respectively. The
      effective rate in the moxibustion group was obviously higher than that in the
      control group (P<0.05). After the treatment, the TCM symptom scores were
      significantly decreased, and the MMSE, ADL and MoCA scores considerably increased
      in both groups compared with those of their own individual pre-treatment
      (P<0.01). The TCM symptom score of the moxibustion group was significantly lower,
      and the MMSE and ADL scores were obviously higher than those of the control group
      (P<0.01). The serum IGF-1 content in both groups was significantly increased
      after the treatment relevant to that of their own individual pre-treatment
      (P<0.01), and was obviously higher in the moxibustion group than in the control
      group (P<0.01). No significant difference was found between the two groups in the
      MoCA score after the treatment (P>0.05).. CONCLUSION: "Huayu Tongluo" moxibustion
      has a positive effect for patients with VCI, which may be associated with its
      effect in up-regulating serum IGF-1 level.

PMID- 30232859
TI  - [Progress of Experimental Researches on Mechanisms of Acupuncture Underlying
      Improvement of Ischemic Cerebral Vascular Disease by Regulating Different
      Intracellular Signaling Pathways].
AB  - China is in the "high death zone" of the world cerebrovascular disease (CVD) map.
      The prevention and treatment of ischemic CVD (ICVD) have become the top priority
      in clinical practice. It has been demonstrated that acupuncture therapy has a
      positive role in bettering clinical symptoms of ICVD patients. Findings of recent
      experimental studies displayed that electroacupuncture (EA) intervention is
      effective in reducing the cerebral infarcted volume and cellular injury,
      promoting proliferation, migration and differentiation of nerve stem cells,
      facilitating the regeneration of nerve tissue, bettering dysneuria and limb
      locomotor ability, etc. in ICVD rats, which are closely associated with its
      effects in regulating different intracellular signaling pathways. In the present
      study, we review the progress of recent experimental studies on the underlying
      mechanisms of EA in improving ICVD from six major signaling pathways including
      Notch, mitogen-activated protein kinases (MAPK)/ extracellular signal regulated
      protein kinases (ERK), phosphatidy linositol-3-kinase (PI 3 K)/ protein kinase B
      (Akt), Janus kinase-signal transducer and activator of transcription (JAK-STAT),
      erythropoietin-producing hepatocyte receptor (Eph)/Ephrin, nuclear factor of
      kappa B (NF-kappaB) and their compositions, which may provide new therapeutic
      targets for acupuncture treatment of ICVD. More attention should be paid to the
      comparison of the efficacy of acupuncture of different acupoint combinations
      (traditional acupoint formulas) in relieving ICVD.

PMID- 30232860
TI  - [High Mobility Group Box 1/ CD 24 Receptor/beta-EP Signaling in "Zusanli" (ST 36)
      Region Contributes to Electroacupuncture Analgesia in Rats with Neuropathic
      Pain].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of
      high mobility group box 1 (HMGB 1) and its receptor CD 24 proteins and beta
      endorphin (beta-EP) content in "Zusanli" (ST 36) region in rats with chronic
      constriction injury (CCI), so as to explore its mechanisms underlying pain
      relief. METHODS: Thirty male Wistar rats were rando-mized into control, CCI model
      and EA groups (n= 10 rats in each). The neuropathic pain model was established by
      ligature of the left sciatic nerve to induce CCI in the model and EA groups, and
      sham operation was performed in rats of the control group. Paw with drawal
      latency (PWL, thermal pain threshold) of the bilateral hind-limbs was detected by
      using an algesia-detector. Eight days after CCI operation, EA was applied to
      bilateral "Zusanli" (ST 36) and "Yanglingquan" (GB 34) for 30 min, once daily for
      5 days. The acetylated-HMGB 1 expression was determined by immunoprecipitation,
      and the expression of HMGB 1 and toll like receptor 4 (TLR 4) proteins and CD 24
      mRNA were detected using Western blot and fluorescent quantitative real time-PCR,
      respectively, and the content of beta-EP in the acupoint region was assayed by
      enzyme linked immunosorbent assay (ELISA). Anti-CD 24 neutralizing antibody (200
      uL, 100 ug/mL) was injected into ST 36 region once daily for 3 days for verifying
      the involvement of HMGB 1/CD 24 signaling in EA analgesia. RESULTS: Compared with
      the control group, the bilateral PWL difference values in the other two groups
      were significantly increased (P<0.05), meaning an occurrence of hyperalgesia
      after CCI. In comparison with the CCI model group, the hyperalgesia in the EA
      group was obviously decreased (P<0.05). After CCI, the expression levels of HMGB
      1 and TLR 4 proteins were considerably increased compared with those in the
      control group (P<0.05). After 5-times' EA, the acetylated-HMGB 1, the expression
      of CD 24 mRNA, and the content of beta-EP were notably up-regulated (P<0.05), and
      there were no obvious changes in the expression levels of HMGB 1 and TLR 4
      proteins (P>0.05). After local injection of anti-CD 24 antibody, EA-induced
      increases of beta-EP content and reduction of thermal pain threshold were
      significantly suppressed (P<0.05). CONCLUSION: EA of ST 36 and GB 34 can
      alleviate neuropathic pain in CCI rats, which is associated with its effects in
      up-regulating beta-EP content, and HMGB 1 protein and CD 24 mRNA expression
      levels in ST 36 region. The activated HMGB 1/CD 24/beta-EP signaling contributes
      to EA-ST 36 induced analgesia.

PMID- 30232861
TI  - [Effect of Electroacupuncture at Different Acupoints on Steroid Hormones and
      Ovarian Androgen Receptor Expression in Polycystic Ovary Syndrome Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) at different
      acupoints on hyperandrogenism and ovarian androgen receptor (AR) expression in
      rats with polycystic ovary syndrome (PCOS), so as to explore its mechanisms
      underlying improvement of PCOS. METHODS: Sixty female SD rats were randomly
      divided into control, model, Zusanli (ST 36), Sanyinjiao (SP 6), Guanyuan (CV 4)
      and comprehensive groups (10 rats/group). The PCOS model was established by
      giving (gavage) the animals with Letrozole solution (1.0 mg/kg), once daily for
      21 consecutive days. EA stimulation was applied to ST 36, SP 6, or CV 4
      respectively, once daily for 14 days. The comprehensive group was treated by EA
      treatment of the abovementioned three acupoints in the meantime. Before and after
      the treatment, the body mass and the ovary weight were measured. The
      morphological structure of the ovary was observed under microscope after H.E.
      staining. The levels of serum hormone and sex hormone binding globulin (SHBG)
      were assayed by ELISA. Free androgen index (FAI) was calculated and the
      expression of AR in the ovary was detected by immunohistochemistry. RESULTS:
      After modeling, the body mass, ovary weight, serum testosterone (T) and FAI
      levels and the expression of AR protein in late ovarian follicles were
      significantly increased (P<0.01, P<0.05), and serum estradiol (E2) and SHBG
      contents were significantly decreased relevant to the control group (P<0.01).
      Following EA intervention and compared with the model group, the body weight of
      each EA group was significantly reduced (P<0.05), the ovarian pathological
      changes were improved, and serum T and FAI levels were significantly decreased
      (P<0.01), and serum E2 and SHBG contents significantly increased in the ST 36, CV
      4 and comprehensive groups (P<0.01, P<0.05). The ovary weight of only CV 4 group
      was significantly lower than that of the model group (P<0.01). The expression of
      AR protein in late follicles of both CV 4 and SP 6 groups was markedly decreased
      (P<0.05, P<0.01). CONCLUSION: EA at ST 36, SP 6, and CV 4 all can improve the
      hyperandrogenism and ovarian polycystic morphological changes of PCOS rats, while
      different acupoints have different functional characteristics.

PMID- 30232863
TI  - [Scalp-acupuncture Improves Neurological Function by Regulating Expression of NF
      kappaB p 65 mRNA, IkappaB mRNA and IL-1 beta and TNF-alpha in Parahippocampal
      Gyrus of Cerebral Ischemia Rats].
AB  - OBJECTIVE: To observe the effect of scalp-acupuncture intervention on the
      expression of parahippocampal factor-kappaB p 65 mRNA (NF-kappaB p 65 mRNA),
      IkappaB mRNA, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF
      alpha) in rats with cerebral ischemia (CI), so as to investigate its molecular
      mechanisms underlying improving CI by reducing inflammatory response. METHODS: A
      total of 64 SD rats were randomized into normal control, model, medication and
      scalp-acupuncture groups, with 16 rats in each group. The focal CI model was
      established by middle cerebral artery occlusion (MCAO). Intraperitoneal injection
      of Pyrrolidine Dithiocarbamate (100 mg*kg-1*d-1) was administrated for rats in
      the medication group, once a day for 7 days. For rats of the scalp-acupuncture
      group, the acupuncture needles were rapidly inserted into bilateral
      Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), followed by twirling the
      needles at 200 cycles/min for 1 min, once again every 10 min during 30 min's
      needle retention. The treatment was conducted once a day for 7 days. The
      neurologic deficit score (0-5 points, impaired consciousness, death, etc.) and
      neurological function score (motor, sensory and sensory tests, 0-10 points) were
      assessed according to Longa's (1989) and Schabitz's (2004) methods, respectively.
      The expression levels of NF-kappaB p 65 mRNA and IkappaB mRNA in the
      parahippocampus gyrus tissue were detected by fluorescence quantitative reverse
      transcription-PCR, and IL-1 beta and TNF-alpha proteins in the parahippocampus
      gyrus tissue were detected by immunohistochemistry. RESULTS: After modeling, the
      neurologic deficit and neurological function scores and the expression levels of
      NF-kappaB p 65 mRNA, IL-1 beta and TNF-alpha in the parahip-pocampus were
      significantly increased in the model group than in the normal group (P<0.01),
      while the expression of IkappaB mRNA was considerably down-regulated (P<0.01).
      Following treatment intervention, the neurologic deficit and neurological
      function scores as well as NF-kappaB p 65 mRNA, and IL-1 beta and TNF-alpha
      protein expression were significantly decreased in both scalp-acupuncture and
      medication groups compared with the model group (P<0.05, P<0.01), and the
      decreased expression of IkappaB mRNA was obviously increased (P<0.05)..
      CONCLUSION: Scalp-acupuncture can improve neurologic function in cerebral
      ischemic rats, which is related with its effects in up-regulating the expression
      of IkappaB to inhibit the dissociation of NF-kappaB, then decreasing the
      expression of IL-1 beta and TNF-alpha (reducing inflammatory response) in the
      parahippocampal gyrus tissue.

PMID- 30232862
TI  - [Time-dependent Protective Effect of Electroacupuncture on Ischemic Myocardium
      and Changes of Myocardial Autophagy and Apoptosis Related Protein Expression in
      Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) at different time
      points on the injured myocar-dium and expression of myocardial Bax/Bcl-2 and Lc 3
      II/I proteins in acute myocardial ischemia-reperfusion injury (MIRI) rats so as
      to explore its mechanisms underlying myocardial protective effect via reducing
      cardiomyocyte autophagy and apoptosis. METHODS: A total of 66 adult SD rats were
      randomly divided into sham operation (sham), model, EA-R 0min(R= reperfusion), EA
      R 30min, EA-R 60min, and EA-R 120min groups, with 6 rats being in the sham group
      and 12 rats being in each of the other 5 groups. The MIRI model was prepared by
      ligating the anterior descending branch (ADB) of the left coronary artery for 30
      min followed by reperfusion for 4 h. In the sham group, the ADB was only threaded
      without ligation. EA was applied to bilateral "Neiguan" (PC 6) for 20 min at 0,
      30, 60, and 120 min when reperfusion. Evans Blue-triphenyltetrazolium chloride
      (TTC) double staining was performed to determine the myocardial infarction area
      (MIA) and the ratio of the infarct size of the area at risk (IS/AAR). ELISA was
      performed to measure serum cardiac troponin 1 (cTn-I) content, and Western blot
      was used to measure the expression of apoptosis-related proteins Bax and Bcl-2
      and autophagy related proteins Lc 3 II and Lc 3 I in the left cardiac ventricle
      tissue. RESULTS: Compared with the model group, the percentages of MIA in the EA
      R 30min, EA-R 60min, and EA-R 120min groups, and the IS/AAR in the EA-R 0min, EA
      R 30min, EA-R 60min and EA-R 120min groups were significantly reduced (P<0.05,
      P<0.01). Comparison among the 4 EA groups showed that the percentages of MIA and
      the IS/AAR were considerably lower in the EA-R 30min, EA-R 60min, and EA-R 120min
      groups than in the EA-R 0min group (P<0.05, except IS/AAR in the EA-R 120min
      group), but significantly higher in the EA-R 60min and EA-R 120min groups than in
      the EA-R 30min group (P<0.05, P<0.01), suggesting a better therapeutic effect of
      EA intervention at 30 min of MIRI in improving MI. In comparison with the sham
      group, myocardial cTn-I content and Bax/Bcl-2 and Lc 3 II/I levels in the model
      group were significantly increased (P<0.01). After EA intervention, the increased
      cTn-I content and Bax/Bcl-2 and Lc 3 II/I levels in the EA-R 0min, EA-R 30min, EA
      R 60min, and EA-R 120min groups were significantly reduced (P<0.05, P<0.01). The
      cTn-I content was obviously lower at EA-R 30 min, but markedly increased at EA-R
      120min than at EA-R 0min (P<0.05). The expression of Bcl-2 was obviously higher
      at EA-R 30min than at EA-R 0min (P<0.05). No significant differences were found
      among the 4 EA intervention time-points in the levels of Bax/Bcl-2 and Lc 3 II/I
      (P>0.05). CONCLUSION: EA intervention can reduce MIA in MIRI rats, which is
      possibly closely related to its effects in reducing apoptosis and autophagy. The
      best intervention time is at 30 min after MI reperfusion, but the difference of
      effects of EA at different time-points is independent of Bax/Bcl-2 and Lc 3 II/I
      expression.

PMID- 30232864
TI  - [Acupuncture Intervention Improves Behavior Reactions and Learning-memory Ability
      in Post-traumatic Stress Disorder Rats].
AB  - OBJECTIVE: To observe the therapeutic effect of acupuncture in the treatment of
      post-traumatic stress disorder (PTSD)-induced abnormal behavior reactions and
      learning-memory ability in rats with traumatic injury. METHODS: Sixty male SD
      rats were randomly divided into control, model, model+animal capturing
      (capturing), medication and acupuncture groups (n=12 rats in each). The PTSD
      model was established by "electric shock plus incarceration" method. Acupuncture
      was applied to "Baihui" (GV 20), and unilateral "Neiguan" (PC 6), "Shenmen" (HT
      7) and "Taichong" (LR 3) once daily for 12 days. The rats in the medication group
      were treated by gavage of Paroxetine Hydrochloride solution (0.42 mg/mL), once
      daily for 12 days. The open field test containing horizontal (crossing grid
      lines) and rearing tests was performed for examining the rats' locomotor activity
      and anxiety-like behavior; and location navigation (escape latency) and special
      probe tests (platform quadrant crossing times) of Morris water maze tasks were
      detected for assessing the rats' learning-memory ability. On day 12 of the
      experiments, the rats were submitted to 3 consecutive sessions of open field
      tests for observing the time of familiar objects (TF) and the time of novelty
      object (TN) of exploration in 5 min (an object-location and an object-recognition
      tasks), followed by calculating the discrimination index [DI=(TN
      TF)/(TN+TF)x100%]. RESULTS: After modeling, compared with the control group, the
      numbers of crossed grids and rearing, and DI were significantly decreased
      (P<0.05), while the number of fecal pellets and escape latency were significantly
      increased in both the model and capturing groups (P<0.05). After the
      intervention, the number of both crossed grids and rearing, platform quadrant
      crossing times, and DI were considerably increased (P<0.05), and the rats' escape
      latency and fecal pellet number were obviously decreased in both medication and
      acupuncture groups relevant to the model and capturing groups (P<0.05). No
      significant differences were found between the acupuncture and medication groups
      in the above mentioned 5 indexes (P>0.05).. CONCLUSION: Acupuncture can
      effectively reduce anxiety-like behavior and improve the impaired learning-memory
      ability in PTSD rats.

PMID- 30232865
TI  - [Effect of Acupuncture Combined with Rehabilitation on Immune and Neural
      Functions in Elderly Patients with Stroke].
AB  - OBJECTIVE: To investigate the therapeutic effect of acupuncture combined with
      rehabilitation and neuro-immune functional activities in elderly patients with
      stroke. METHODS: A total of 196 elderly stroke patients were randomly divided
      into control (rehabilitation exercise) and observation(acupuncture+
      rehabilitation exercise)groups (n=98 in each). Patients of the control group were
      treated by general healing treatment including good limb placement, timely
      conversion of body position, joint-motor exercise, sitting balance exercise,
      sitting-standing-walking, walking up and down stairs, daily life ability
      exercise, etc. and those of the observation group were treated by using the same
      methods mentioned in the control group and manual acupuncture stimulation of
      Sishencong (EX-HN 1), Xuanli (GB 6), the midpoint of EX-HN 1 and GB 6, Baihui (GV
      20), Qubin (GB 7), and the midpoint between GV 20 and GB 7 on the affected side
      (once a day for three 10-day courses). Serum interleukin-2 (IL-2), interleukin-6
      (IL-6), tumor necrosis factor-alpha (TNF-alpha), and high-sensitive C-reactive
      protein (hs-CRP) contents were assayed using ELISA, and serum CD 3+, CD 4+ and CD
      8+ contents assayed using flow cytometry. The disability severity was assessed by
      using National Institutes of Health Stroke Scale (NIHSS, for dysneuria), modified
      Rankin Scale,(mRS, stroke severity), and Barthel Index (BI, performance in
      activities of daily living), separately. The therapeutic effect was determined
      according to NIHSS score, clinical symptoms and daily activity ability. RESULTS:
      On day 30 after the treatment, serum IL-2, IL-6, TNF-alpha and hs-CRP contents
      were significantly decreased in the observation group in comparison with its own
      pre-treatment and day 10 after the treatment, and on day 10 and 30 after the
      treatment, the above were lower than the control group (P<0.05). On day 30 after
      the treatment, serum CD 3+, CD 4+ and CD 4+/CD 8+ levels were significantly
      increased in both control and observation groups in comparison with their own pre
      treatment and 10 days' treatment (P<0.05), while CD 8+ levels obviously decreased
      in both groups relevant to their own pre-treatment and 10 days' treatment
      (P<0.05), and the increased CD 3+, CD 4+ and CD 4+/CD 8+ levels were significant
      higher in the observation group than in the control group (P<0.05), and the CD 8+
      level was obviously lower in the control group than in the observation group
      (P<0.05). On day 30 after the treatment, the NIHSS and mRS scores were
      significantly decreased in both groups (P<0.05), and significantly lower in the
      observation group than in the control group (P<0.05); the BI scores were
      evidently increased in both groups relevant to their own pre-treatment (P<0.05),
      and the BI level was considerably higher in the observation group than in the
      control group (P<0.05). The total effective rate was 72.4% (71/98) and 93.9%
      (92/98) respectively in the control and observation groups, being obviously
      higher in the latter group than in the former (P<0.05). CONCLUSION: Acupuncture
      combined with rehabilitation therapy is effective in promoting the recovery of
      neurological function and in regulating T lymphocyte subsets and the expression
      of inflammatory factors in elderly patients with stroke.

PMID- 30232866
TI  - [Comparison of Therapeutic Effects Between Thermosensitive Moxibustion and
      Medication in the Treatment of Insomnia of Liver-Qi Stagnation Pattern].
AB  - OBJECTIVE: To compare the therapeutic effect of thermosensitive moxibustion (TSM)
      and medication in the treatment of insomnia patients with the syndrome of
      stagnation of liver-qi. METHODS: A total of 60 insomnia patients with the
      syndrome of liver-qi stagnation were randomly divided into TSM group and
      medication group (n = 30 in each). Mild moxibustion was applied to bilateral
      Taichong (LR 3) and Qiuxu (GB 40) alternatively till the patient experienced an
      intense warmth (diathermic, heat transmission, etc.) feeling in the local region.
      The treatment was conducted once daily for 15 d. Patients of the medication group
      were ordered to take Estazolam tablets (1 mg/d) 1 h before sleeping, once daily
      for successive 15 days. The sleep quality (sleeping quality, falling asleep time,
      sleep duration, sleep efficiency, sleep disorders, hyponotic and day time
      dysfunction, 0-21 points) was evaluated by using Pittsburgh Sleep Quality Index
      (PSQI). The therapeutic effect was assessed in accordance with the "Guide
      Principles for Clinical Trials on New Drugs of Chinese Materia Medica (1993)" and
      international united sleep efficiency value. RESULTS: Following the treatment,
      the PSQI of both groups were significantly decreased relevant to their own pre
      treatment (P<0.05), but without significant difference between the two groups
      (P>0.05). Of the two 30 cases in the medication and moxibustion groups, 12
      (40.00%) and 20 (66.67%) had marked improvement, 7 (23.33%) and 6 (20.00%) were
      effective, and 11(36.67%) and 4 (13.33%) were invalid, with the effective rates
      being 63.33 % (19/30) and 86.67% (26/30), respectively. The effective rate of the
      TSM group was significantly higher than that of the medicine group (P <0.05).
      CONCLUSION: Thermosensitive moxibustion applied to the source points of the Liver
      and Gallbladder Meridians can improve the quality of sleep in insomnia patients
      with syndrome of liver-qi stagnation.

PMID- 30232867
TI  - [A Potential Role of Adenosine A 2 b Receptor in Mediating Acupuncture
      Pretreatment Induced Cardioprotection via Influencing Intracellular Calcium
      Regulator].
AB  - It has been shown that ischemia preconditioning (IPC) can attenuate the
      myocardial injury induced by ischemic and reperfusion. But it was rarely used in
      clinic due to its inoperability. Previous studies indicate that
      electroacupuncture (EA) pretreatment can mimic myocardial ischemia
      preconditioning (MIPC) to produce cardioprotective effect. The activated
      adenosine A 2 b receptor has been proven to be involved in mediating the
      cardioprotection of IPC. In the studies on acupuncture analgesia, it was reported
      that adenosine receptor was activated by acupuncture stimulation, and acupuncture
      pretreatment can affect the acti-vities of intracellular A 2 b receptor. Based on
      those mentioned above, it is highly likely that the A 2 b receptor may also
      participate in the cardioprotection produced by acupuncture pretreatment. In this
      paper, we comprehensively reviewed relevant studies regarding 1) the
      cardioprotective effect of IPC and its limitations, 2) the similar
      cardioprotection produced by both acupuncture pre-treatment and IPC, 3) the
      mechanism underlying myocardial ischemic injury and intracellular calcium
      regulation, 4) the acti-vation of adenosine receptors and effects of acupuncture,
      5) the relationship between adenosine receptors and intracellular calcium ion,
      and 6) the effect of acupuncture on adenosine receptors, so as to provide a novel
      assumption that A 2 b receptor may be a key factor in mediating the
      cardioprotection of acupuncture pretreatment. Our future research will
      systematically explore the me-chanism of acupuncture pretreatment in protecting
      ischemic myocardium from myocardial cell adenosine A 2 b receptor and
      intracellular calcium signal transduction related factors.

PMID- 30232868
TI  - [Application of Laser Scanning Confocal Microscope to Morphologic Research of
      Acupuncture and Moxibustion].
AB  - Laser scanning confocal microscope (LSCM) has been used in the field of
      morphological research of acupuncture and moxibustion for more than 20 years. It
      is one of the important tools for revealing the structure of acupoints and the
      effect of acupuncture from histological perspective. With the help of technical
      advantages of LSCM, the quality of morphological research of acupuncture and
      moxibustion has been greatly improved, helping us gain a deeper understanding
      about the structure of acupoints and meridians as well as histochemical changes
      induced by acupuncture/moxibustion intervention. In order to promote the
      application of LSCM in acupuncture and moxibustion, we simply reviewed some
      recent studies in this field and combined them with our experience, trying to
      provide some technical suggestions. We expect that the technique of LSCM could be
      integrated into more experiments in acupuncture medicine to provide more powerful
      morphological evidence for exploring the underlying mechanisms of acupuncture and
      moxibution therapies.

PMID- 30232869
TI  - [Regularity of Acupoint Selection for Simple Obesity Treated by Acupoint Catgut
      Embedding Based on Complex Network Technology].
AB  - OBJECTIVE: To analyze the core acupoints and acupoint combinations of catgut
      embedding for simple obesity based on the complex network technology. METHODS:
      Articles about acupoint catgut embedding for simple obesity were collec-ted from
      databases of PubMed, CNKI, Wanfang and VIP from 1980 to 2016 by using keywords
      "simple obesity" "obesity" "acupoint embedding" "acupuncture" and "traditional
      Chinese medicine", followed by constructing a database of acupoint prescription.
      Acupoint node (one node means an acupoint) weighted complex network was
      constructed by using complex network technique, followed by conducting centrality
      analysis and clustering analysis about the nodes using Matlab 2014, a software
      for revealing the core acupoint node and compatibility relations. At last,
      theresults (complex network diagram) were displayed using software Gephi 0.9.1.
      RESULTS: A total of 238 articles (all in Chinese) including 278 acupoints (of
      which 115 are meridian acupoints) were collected. The top 15 core acupoints are
      Tianshu (ST 25), Zusanli (ST 36), Zhongwan (CV 12), Fenglong (ST 40), San-yinjiao
      (SP 6), Quchi (LI 11), Yinlingquan (SP 9), Guanyuan (CV 4), Pishu (BL 20), Qihai
      (CV 6), Shenshu (BL 23), Shangjuxu (ST 37), Daheng (SP 15), Shuifen (CV 9), and
      Ganshu (BL 18), mainly distributing in the abdomen, lower limbs and back. Those
      acupoints with the highest core degree are attributed to the Stomach Meridian,
      Conception Vessel, Bladder Meri-dian, Spleen Meridian and Large Intestine
      Meridian. Regarding the compatibility of these acupoints, ST 25 and CV 12 have
      the highe-st correlation frequency, followed by ST 25 and ST 36, and ST 40 and ST
      25, indicating the principle of different combinations being regional acupoints
      and meridian acupoints. CONCLUSION: In the treatment of simple obesity with
      catgut embedding, top 15 core acupoints as ST 25, ST 36, CV 12, ST 40, etc, and
      acupoint recipes as ST 25 and CV 12, ST 25 and ST 36, ST 40 and ST 25 are most
      frequently used in clinical practice.

PMID- 30232870
TI  - [A Meta-analysis of Effectiveness of Acupoint Catgut Embedding Therapy for
      Insomnia].
AB  - OBJECTIVE: To evaluate the effectiveness and superiority of acupoint catgut
      embedding in the treatment of insomnia. METHODS: Randomized controlled trials
      (RCTs) for insomnia treated by acupoint implantation of catgut were included in
      the present study. We searched the related articles from 6 databases (PubMed,
      Google Scholar, CBM, CNKI, VIP and Wanfang) from the date of inception to March
      19, 2017 by using keywords "catgut implantation at acupuncture point" or "catgut
      implantation at acupoint" and "insomnia" or "agrypnia" and "randomised (or
      randomized) clinical trial". Quality assessments were performed by two
      researchers independently using GRADE profile 3.6, followed by crosscheck. Data
      were analyzed using software Revman 5.3 and STATA 14.0. RESULTS: Twenty-two
      trials met the inclusion criteria were included. They recruited 1 714 cases of
      insomnia. GRADE grading suggests a low quality of these articles. Heterogeneous
      test (numerical test) showed chi2=31.11, P=0.07, I2=32%. Gabriz chart and
      sensitivity analysis ultimately determined that these trials have smaller or no
      heterogenity. The effective rate of acupoint catgut embedding for insomnia was
      higher than that of the control group (OR= 3.77; 95% CI: 2.63-5.41; P<0.00001).
      CONCLUSION: Acupoint catgut embedding therapy has a positive role in clinical
      treatment of insomnia. But due to lower quality of current literature, more high
      quality randomized controlled clinical trials are required.

PMID- 30232871
TI  - [Progress of Researches on Brain Mechanism Underlying Regulatory Effect of
      Acupuncture Intervention on Visual Plasticity of Amblyopia].
AB  - Acupuncture therapy has a positive effect in the treatment of amblyopia. This
      article summarizes findings of the research on brain mechanisms underlying the
      regulatory effect of acupuncture on visual plasticity of amblyopia. In a multi
      system and multi-level viewpoints, we elaborated brain mechanism underlying the
      regulatory effect of acupuncture on visual plasticity in amblyopia from the
      perspective of ultrastructure, plasticity, electrical activities, neural coding
      and visual microcirculation of the neurons of the visual cortex, and the
      targeting points from the visual center to the effector organ.

PMID- 30232872
TI  - [Progress of Research on Mechanism of Acupuncture for Diabetes Mellitus].
AB  - Acupuncture has been used to treat diabetes mellitus (DM) for more than one
      thousand years. In the present paper, we review new progress of researches on the
      underlying mechanism of acupuncture intervention for DM. Results showed that
      acupuncture intervention can relieve DM by 1) reducing body weight through up
      regulating leptin level, suppressing insulin resistance and appetite to reduce
      food intake possibly by way of down-regulating expression of neuropeptide Y in
      the hypothalamus, retarding gastric emptying velocity, increasing small
      intestinal peristalsis, raising plasma levels of glucagon-like peptide-1 (GLP-1)
      and peptide YY, etc.; 2) improving pancreas function, raising insulin sensitivity
      to improve insulin resistance possibly by activating AMP-activated protein kinase
      and sirtuin 1/ peroxisome proliferator-activated receptor gamma coactivator 1
      alpha signaling, up-regulating activities of cholinergic nerve activity and
      nitric oxide synthase, and inhibiting apoptosis of pancreatic beta-cells; 3)
      lowering blood glucose possibly by increasing anaerobic glucose metabolism,
      regulating activities of vagal and sympathetic nerves; 4) adjusting the levels of
      related hormones such as melatonin, insulin, glucocorticold, epinephrine, etc.
      Moreover, acupuncture treatment combined with hypoglycemic drugs has a synergic
      effect in lowering blood glucose, suggesting a potentially effective approach for
      improving DM and being worthy of further studying in clinical practice.

PMID- 30232873
TI  - Vertically Oxygen-Incorporated MoS2 Nanosheets Coated on Carbon Fibers for Sodium
      Ion Batteries.
AB  - Developing a high-performance anode with high reversible capacity, rate
      performance, and great cycling stability is highly important for sodium-ion
      batteries (SIBs). MoS2 has attracted extensive interest as the anode for SIBs.
      Herein, the vertically oxygen-incorporated MoS2 nanosheets/carbon fibers are
      constructed via a facile hydrothermal method and then by simple calcination in
      air. Oxygen incorporation into MoS2 can increase the defect degree and expand the
      interlayer spacing. Vertical MoS2 nanosheet array coated on carbon fibers not
      only can expose rich active sites and reduce the diffusion distance of Na+, but
      also improve the electronic conductivity and enhance structural stability.
      Meanwhile, interlayer-expanded MoS2 can decrease Na+ diffusion resistance and
      increase accessible active sites for Na+. In this work, the electrode combining
      the oxygen-incorporated strategy with vertical MoS2 nanosheet-integrated carbon
      fibers displays high specific capacities of 330 mAh g-1 over 100 cycles at a
      current density of 0.1 A g-1 together with excellent rate behavior as the anode
      for SIBs. This strategy offers a helpful way for improving the electrochemical
      performance.

PMID- 30232874
TI  - Structural and Functional Interaction of Delta9-Tetrahydrocannabinol with Liver
      Fatty Acid Binding Protein (FABP1).
AB  - Although serum Delta9-tetrahydrocannabinol (Delta9-THC) undergoes rapid hepatic
      clearance and metabolism, almost nothing is known regarding the mechanism(s)
      whereby this highly lipophilic phytocannabinoid is transported for
      metabolism/excretion. A novel NBD-arachidonoylethanolamide (NBD-AEA) fluorescence
      displacement assay showed that liver fatty acid binding protein (FABP1), the
      major hepatic endocannabinoid (EC) binding protein, binds the first major
      metabolite of Delta9-THC (Delta9-THC-OH) as well as Delta9-THC itself. Circular
      dichroism (CD) confirmed that not only Delta9-THC and Delta9-THC-OH but also
      downstream metabolites Delta9-THC-COOH and Delta9-THC-CO-glucuronide directly
      interact with FABP1. Delta9-THC and metabolite interaction differentially altered
      the FABP1 secondary structure, increasing total alpha-helix (all), decreasing
      total beta-sheet (Delta9-THC-COOH, Delta9-THC-CO-glucuronide), increasing turns
      (Delta9-THC-OH, Delta9-THC-COOH, Delta9-THC-CO-glucuronide), and decreasing
      unordered structure (Delta9-THC, Delta9-THC-OH). Cultured primary hepatocytes
      from wild-type (WT) mice took up and converted Delta9-THC to the above
      metabolites. Fabp1 gene ablation (LKO) dramatically increased hepatocyte
      accumulation of Delta9-THC and even more so its primary metabolites Delta9-THC-OH
      and Delta9-THC-COOH. Concomitantly, rtPCR and Western blotting indicated that LKO
      significantly increased Delta9-THC's ability to regulate downstream nuclear
      receptor transcription of genes important in both EC ( Napepld > Daglb > Dagla,
      Naaa, Cnr1) and lipid ( Cpt1A > Fasn, FATP4) metabolism. Taken together, the data
      indicated that FABP1 may play important roles in Delta9-THC uptake and
      elimination as well as Delta9-THC induction of genes regulating hepatic EC levels
      and downstream targets in lipid metabolism.

PMID- 30232875
TI  - Synthesis of Acridines from o-Aminoaryl Ketones and Arylboronic Acids by Copper
      Trifluoroacetate-Mediated Relay Reactions.
AB  - An efficient and practical method for the synthesis of medicinally important
      acridines from readily available o-aminoaryl ketones and arylboronic acids was
      developed using copper(II)-mediated relay reactions that involve intermolecular
      Chan-Lam cross-coupling and subsequent intramolecular Friedel-Crafts-type
      reactions. A sole promoter, i.e., Cu(OTf)2, was used; therefore, strongly acidic
      and basic conditions, nonreadily available or expensive substrates, additives,
      and noble-metal catalysts were not needed.

PMID- 30232876
TI  - Sn-Co Nanoalloys Encapsulated in N-Doped Carbon Hollow Cubes as a High
      Performance Anode Material for Lithium-Ion Batteries.
AB  - To address the huge volumetric change and unstable solid electrolyte interphase
      (SEI) issues of Sn-based anodes, this paper proposes a Sn-Co-C ternary composite
      with a cubic yolk-shell structure. The proposed Sn-Co nanoalloys encapsulated in
      N-doped carbon hollow cubes (Sn-Co@C) are simply synthesized by the conformal
      polydopamine coating of home-made CoSn(OH)6 hollow nanocubes subsequent with
      hydrogen reduction. The cubic Sn-Co@C yolk-shell structure possessing an
      optimized carbon shell thickness displays excellent cyclic performance and
      superior rate capability when utilized as an anode for lithium-ion batteries. The
      composite shows an initial discharge capacity of 885 mA h g-1 at 200 mA g-1 with
      a high capacity retention of ~91.2% after 180 cycles. It can still deliver a
      considerable capacity of 560 mA h g-1 at a high current density of 1 A g-1 after
      200 cycles. This attractive electrochemical characteristic can be ascribed to the
      distinct cubic yolk-shell architecture, in which the inner inactive Co can buffer
      the volumetric expansion of Sn, the void can provide external space for the
      volumetric change of Sn, and the outer carbon shell can effectively prevent the
      agglomeration of Sn-Co nanoalloys and maintain the stability of SEI films.

PMID- 30232877
TI  - Oriented-External Electric Fields Create Absolute Enantioselectivity in Diels
      Alder Reactions: Importance of the Molecular Dipole Moment.
AB  - The manuscript studies the enantioselectivity and stereoselectivity of Diels
      Alder (DA) cycloadditions between cyclopentadiene (CPD) and a variety of
      dienophiles (ranging from halo-ethenes to cyano-ethenes), under oriented external
      electric fields (OEEFs). Applying OEEFs oriented in the X/ Y directions,
      perpendicular to the reaction axis ( Z), will achieve complete isomeric and
      enantiomeric discrimination of the products. Unlike the Z-OEEF, which involves
      charge-transfer from the diene to the dienophile, and thereby brings about
      catalysis due to increased intramolecular bonding, an OEEF along X, aligned
      parallel to the C1-C4 atoms of CPD, will lead to R/ S enantiomeric discrimination
      by means of intramolecular-bond polarization. A Y field will discriminate
      endo/exo stereoisomers in a similar mechanism. The XY field-combination will
      resolve both R/S and endo/exo. The resolution is complete and can be achieved at
      will by flipping the direction of the field along the X and Y axes. The
      preconditions for achieving the enantiomeric and isomeric discrimination are
      discussed and require fixing of the CPD onto a surface. In so doing the chiral
      discrimination is achieved by dipole-moment selection rules, such that the field
      filters out one of the enantiomers, which is highly raised in energy by dipole
      selection. The dependence of the discrimination on the polarity of the
      dienophiles leads to a predictive trend.

PMID- 30232878
TI  - Effect of Titanium Dioxide on Secondary Organic Aerosol Formation.
AB  - Secondary organic aerosol (SOA), a dominant air pollutant in many countries,
      threatens the lives of millions of people. Extensive efforts have been invested
      in studying the formation mechanisms and influence factors of SOA. As promising
      materials in eliminating air pollutants, the role of photocatalytic materials in
      SOA formation is unclear. In this study, TiO2 was employed to explore its impact
      on SOA formation during the photooxidation of m-xylene with NO x in a smog
      chamber. We found that the presence of TiO2 strongly suppressed SOA formation.
      The yields of SOA in the photooxidation experiments of m-xylene with NO x were
      0.3-4%, whereas negligible SOA was formed when TiO2 was added. When ((NH4)2SO4)
      was introduced as seed particles, the presence of TiO2 decreased the yields of
      SOA from 0.3-6% to 0.3-1.6%. The sharply decreased concentrations of reactive
      carbonyl compounds were the direct cause of the suppression effect of TiO2 on SOA
      formation. However, the suppression effect was influenced by the addition of seed
      particles and the initial concentration of NO x. Reaction mechanisms of the
      photocatalysis of m-xylene with and without NO x were proposed.

PMID- 30232880
TI  - Consider Fjord-Assisted Carbon Storage.

PMID- 30232879
TI  - Cross-Species Molecular Imaging of Bile Salts and Lipids in Liver: Identification
      of Molecular Structural Markers in Health and Disease.
AB  - The liver is the primary organ involved in handling of bile salts, a class of
      amphipathic molecules with signaling activities as well as desired and
      detrimental detergent actions. To allow in-depth investigation of functions of
      bile salts in healthy and diseased liver, the spatial distribution of bile salt
      species within the liver needs to be studied. Therefore, the aim of our study was
      to determine hepatic bile salt distribution and identify specific lipid markers
      that define the structural elements of the liver. Matrix-assisted laser
      desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to monitor
      the spatial distribution of bile salts and lipids in liver sections of rat, dog,
      and patients with unaffected and cholestatic parenchyma. MALDI-MSI in negative
      ion mode showed the local presence of a variety of bile salts, predominantly
      taurine-conjugates, as localized patches of varying sizes (representing the bile
      ducts) throughout the liver tissue. Specific molecular markers were identified
      for the connective tissue (phosphatidic acids, e.g., [PA (18:0_18:1)-H]-), the
      liver parenchyma (phosphatidylinositols, e.g., [PI (18:0_20:4)-H]-), and the bile
      ducts (hydroxylated-sulfatides, e.g., [ST-OH (18:1_24:0)-H]-). One of these
      sulfatides (at m/ z 906.6339) was found to be uniquely localized in a thin lining
      on the inside of the bile duct, colocalized with cytokeratins, and encased
      luminal bile salts. A similar distribution of the aforementioned sulfatide was
      observed, albeit in constricted ductular structures, in the liver of a patient
      with a mild clinical phenotype of primary sclerosing cholangitis (PSC). In
      contrast, sulfatides were virtually absent in the liver of patients with PSC and
      a severe clinical phenotype, with (atypical) cholanoids (e.g., the bile alcohol 5
      cyprinolsulfate) abundant in the extra-ductular space and glyco(cheno)deoxycholic
      acid-3-sulfate localized to fibrotic connective tissue. The latter two molecular
      species were able to discriminate between healthy liver tissue ( n = 3) and
      tissue from PSC patients with a severe clinical phenotype ( n = 3). In
      conclusion, the distinct structural elements of the mammalian liver are
      characterized by specific classes of lipids. We propose that (hydroxylated
      )sulfatides are specific molecular markers of the bile duct.

PMID- 30232881
TI  - Terbium(III) Organic Gels: Novel Antenna Effect-Induced Enhanced
      Electrochemiluminescence Emitters.
AB  - Metal organic gels (MOGs) have emerged as a new class of smart soft materials
      with superb luminescence properties and have attracted tremendous attention in
      various aspects. However, the electrochemiluminescence (ECL) behavior of MOGs has
      not been reported yet. In this work, cathode electrochemiluminescence (ECL)
      emission of terbium(III) organic gels (TOGs) was reported for the first time with
      potassium persulfate (K2S2O8) as an efficient coreactant. TOGs were synthesized
      by a facile one-step strategy, mixing terbium ions (Tb3+) and the ligand 4'-(4
      carboxyphenyl)-2,2':6',2''-terpyridine (Hcptpy) at room temperature. The possible
      strong green ECL emission mechanism was discussed in detail and ascribed to the
      external coreactant enhancement and internal antenna effect enhancement.
      Moreover, the promising application of TOGs in analytical chemistry was clarified
      by the ECL on-off detection of tetracycline. This remarkable discovery of ECL
      emission of TOGs may pioneer the application of MOGs in ECL fields.

PMID- 30232882
TI  - Rare Thioglycosides from the Roots of Wasabia japonica.
AB  - Six new thioglycosides (1-6) were characterized from the roots of Wasabia
      japonica along with a known analogue (7). Of these compounds, 1-3 possess a
      disulfide bridge connecting the carbohydrate motif and the aglycone, which is
      extremely rare in Nature. In particular, compound 1 forms an unusual 1,4,5
      oxadithiocane ring system. The structures of the isolated compounds were
      determined through conventional NMR and HRMS data analysis procedure, and
      computational methods with advanced statistics were used for the configurational
      assignments of 1 and two pairs of inseparable epimers, 2/3 and 4/5. All compounds
      were evaluated for their anti-inflammatory, neuroprotective, and cytotoxic
      activities, with 1 showing weak anti-inflammatory activity (IC50 41.2 MUM).

PMID- 30232883
TI  - Surface-Mediated Aligned Growth of Monolayer MoS2 and In-Plane Heterostructures
      with Graphene on Sapphire.
AB  - Aligned growth of transition metal dichalcogenides and related two-dimensional
      (2D) materials is essential for the synthesis of high-quality 2D films due to
      effective stitching of merging grains. Here, we demonstrate the controlled growth
      of highly aligned molybdenum disulfide (MoS2) on c-plane sapphire with two
      distinct orientations, which are highly controlled by tuning sulfur
      concentration. We found that the size of the aligned MoS2 grains is smaller and
      their photoluminescence is weaker as compared with those of the randomly oriented
      grains, signifying enhanced MoS2-substrate interaction in the aligned grains.
      This interaction induces strain in the aligned MoS2, which can be recognized from
      their high susceptibility to air oxidation. The surface-mediated MoS2 growth on
      sapphire was further developed to the rational synthesis of an in-plane MoS2
      graphene heterostructure connected with the predefined orientation. The in-plane
      epitaxy was observed by low-energy electron microscopy. Transmission electron
      microscopy and scanning transmission electron microscopy suggest the alignment of
      a zigzag edge of MoS2 parallel to a zigzag edge of the neighboring graphene.
      Moreover, better electrical contact to MoS2 was obtained by the monolayer
      graphene compared with a conventional metal electrode. Our findings deepen the
      understanding of the chemical vapor deposition growth of 2D materials and also
      contribute to the tailored synthesis as well as applications of advanced 2D
      heterostructures.

PMID- 30232884
TI  - Migration of Iron Oxide Nanoparticle through a Silica Shell by the Redox
      Buffering Effect.
AB  - This study demonstrates that mineral redox buffer, an important concept in
      geology, can be used to manipulate the migration of nanoparticles and produce
      nanostructures of unexpected morphologies. Using a silica shell as a redox
      buffer, we show that iron oxide nanoparticles can be relocated from inside to the
      outer surface of the silica shell. The migration of iron oxide through silica was
      initiated by manipulation of the oxygen fugacity conditions at an elevated
      temperature. During the treatment, iron oxide was absorbed and then separated
      from the silica shell by the formation and then decomposition of iron silicate
      (Fe2SiO4). Tuning the relative dimensions of the iron oxide core and silica shell
      allows control of the shape of the iron oxide-silica composite structures. It is
      believed that the discovery of the nanoscale redox buffering effect can be
      extended to control the morphological configuration of other multivalent metal
      oxide nanocomposite structures by this particular type of template synthesis
      through manipulation of the chemical-transport properties of nanoscale templates.

PMID- 30232885
TI  - Europium-Based Metal-Organic Framework as a Dual Luminescence Sensor for the
      Selective Detection of the Phosphate Anion and Fe3+ Ion in Aqueous Media.
AB  - A new three-dimensional europium-based metal-organic framework has been
      synthesized with the newly designed ligand L (6-[1-(4-carboxyphenyl)-1 H-1,2,3
      triazol-4-yl]nicotinic acid). This compound acts as a dual sensor for the
      phosphate anion and Fe3+ ion in aqueous media. The mechanistic aspect of this
      selectivity and sensitivity was explored through several spectroscopic methods
      and then correlated with the corresponding structure.

PMID- 30232886
TI  - A Comparative Study of Outer Membrane Proteome between Paired Colistin
      Susceptible and Extremely Colistin-Resistant Klebsiella pneumoniae Strains.
AB  - In the present report we characterized the outer membrane proteome, genomic, and
      lipid A remodelling changes following the evolution of a colistin-susceptible K.
      pneumoniae ATCC 13883 strain into an extremely colistin-resistant strain. Lipid A
      profiling revealed the outer membrane of the colistin-susceptible strain is
      decorated primarily by hexa- and hepta-acylated lipid A species and a minor tetra
      acylated species. In the lipid A profile of the extremely colistin-resistant
      strain, in addition to the aforementioned lipid A species, the obligatory 4-amino
      4-deoxy-l-arabinose modification of the hexa-acylated lipid A was detected.
      Comparative genomic analysis revealed that the mgrB gene of the colistin
      resistant strain is inactivated by a single nucleotide insertion which produces a
      frame-shift, resulting in premature termination. We also detected two synonymous
      mutations in the two-component system genes phoP and phoQ. Comparative profiling
      of the outer membrane proteome of each strain revealed that outer membrane
      proteins from bacterial stress response, glutamine degradation, pyruvate,
      aspartate, and asparagine metabolic pathways were over-represented in the
      extremely colistin-resistant K. pneumoniae ATCC 13883 strain. In comparison, in
      the sensitive strain, outer membrane proteins from carbohydrate metabolism, H+
      ATPase, cell division, and peptidoglycan biosynthesis were over-represented.
      Notably, there were no discernible differences between the OmpK35 and OmpK36
      major outer membrane porins between the polymyxin-susceptible and -resistant
      strains suggesting porin deficiency is not involved in the colistin resistance in
      the ATCC 13883 strain. These findings shed new light on the outer membrane
      remodelling events accompanying the development of extremely high levels of
      colistin resistance in K. pneumoniae.

PMID- 30232887
TI  - Three-Dimensional-Stacked Gold Nanoparticles with Sub-5 nm Gaps on Vertically
      Aligned TiO2 Nanosheets for Surface-Enhanced Raman Scattering Detection Down to
      10 fM Scale.
AB  - Seeking for ultrasensitive and low-cost substrates is highly demandable for
      practical applications of surface-enhanced Raman scattering (SERS) technology. In
      this work, we report an ultrasensitive SERS-active substrate based on wet
      chemistry-synthesized vertically aligned large-area TiO2 nanosheets (NSs)
      decorated by densely packed gold nanoparticles (Au NPs) with sub-5 nm gaps. Via a
      multistep successive deposition process, three-dimensional-stacked Au NPs
      sandwiched by a 3 nm SiO2 layer were assembled onto the TiO2 NS, enabling
      numerous hotspots due to the formation of both ultratiny plasmonic gaps and
      semiconductor/metal interfaces. Experimental results show that the fabricated
      substrate displays a detection limit down to 10 fM (10-14 M) without involving
      any condensation process by using the crystal violet as probe molecules. Control
      experiments and electromagnetic simulations indicate that the nanogaps defined by
      the 3 nm spacer are essential for the obtained excellent SERS performance. With
      its ultrasensitive detection capability, we demonstrate that the fabricated SERS
      substrate can be used for the trace analysis of melamine in milk.

PMID- 30232888
TI  - Fabrication of Integrated Cu2O@HKUST-1@Au Nanocatalysts via Galvanic Replacements
      toward Alcohols Oxidation Application.
AB  - Metastable Cu2O is an attractive material for the architectural design of
      integrated nanomaterials. In this context, the in situ growth of microporous
      metal-organic frameworks (MOFs) on Cu2O nanocrystals with well-defined shapes
      (such as octahedron, truncated octahedron, and corner-truncated cube) was
      conducted under ambient conditions by using sacrificial Cu2O nanocrystals as a
      copper ion source for the construction of HKUST-1. It was found that the growth
      rate of HKUST-1 on the (111) facet of octahedral Cu2O was much faster than that
      on the (100) facet of cubic Cu2O. A subsequent etching process on the core-shell
      structured Cu2O@HKUST-1 to remove Cu2O results in hollow HKUST-1 with
      hierarchical pores, where the shapes of cavities are tailored depending on the
      original Cu2O crystals. Importantly, it was found that the integrated Cu2O@HKUST
      1@Au nanocatalysts could be fabricated by galvanic replacement reaction between
      Cu2O and AuCl4-, wherein the copper(I) ions from Cu2O etching diffuse through the
      microporous MOF shell and reach to the external surface to reduce AuCl4- ions,
      thereby forming Au nanoparticles exclusively on the MOF external surface.
      Furthermore, the catalytic applications of Cu2O@HKUST-1@Au toward liquid-phase
      oxidation of both aromatic and aliphatic alcohols were studied. Notably, 100%
      selectivities of aldehyde products were achieved without any further oxidation
      byproducts such as acid and ester.

PMID- 30232889
TI  - Branch-Migration Based Fluorescent Probe for Highly Sensitive Detection of
      Mercury.
AB  - Detection of heavy metals is of great importance for food safety and
      environmental analysis. Among various heavy metal ions, mercury ion is one of the
      most prevalent species. The methods for detection of mercury were numerous, and
      the T-Hg-T based assay was promising due to its simplicity and compatibility.
      However, traditional T-Hg-T based methods mainly relied on multiple T-Hg-T to
      produce enough conformational changes for further detection, which greatly
      restrained the limit of detection. Hence, we established a branch-migration based
      fluorescent probe and found that single T-Hg-T could produce strong signals. The
      sensing mechanism of our method in different reaction modes was explored, and the
      detection limits were determined to be 18.4 and 14.7 nM in first-order reaction
      mode and mixed reaction mode, respectively. Moreover, coupled with Endonuclease
      IV assisted signal amplification, the detection limit could be 1.2 nM, lower than
      most DNA based fluorometric assays. For practicability, the specificity of our
      assay toward different interfering ions was investigated and detection of Hg2+ in
      deionized water and lake water was also achieved with similar recoveries compared
      to those of atomic fluorescence spectrometry, which demonstrated the
      practicability of our method in real samples. Definitely, the proposed branch
      migration probe would be a promising substitution for current DNA probes based on
      recognition of multiple T-Hg-T and we anticipate it to be widely adopted in food
      and environmental analysis.

PMID- 30232890
TI  - Conformational Effects on Gas-Phase Acidities of Isomeric C3 and C5 Alkanols.
AB  - The competitive threshold collision-induced dissociation technique is used to
      examine conformational effects on the relative gas-phase acidities of selected
      alcohols. By use of HF and H2O as reference acids in a local thermochemical
      network to obtain absolute acidities, the measured 0 K gas-phase acidities for
      the propanol and pentanol isomers are Deltaacid H0(CH3CH2CH2O-H) = 1563.9 +/- 2.9
      kJ/mol, Deltaacid H0((CH3)2CHO-H) = 1568.2 +/- 2.7 kJ/mol, Deltaacid
      H0(CH3(CH2)4O-H) = 1556.4 +/- 2.9 kJ/mol, and Deltaacid H0((CH3)2CHCH2CH2O-H) =
      1556.5 +/- 3.0 kJ/mol. Conformational stabilization during deprotonation results
      in the observed acidity differences between isomers, which can be compared with
      the "intrinsic" acidity strength defined as deprotonation of the extended all-
      anti staggered conformations without relaxation. The intrinsic acidities for the
      propanol and pentanol isomers are 1567 and 1562 kJ/mol, respectively. The
      difference in intrinsic and observed acidity is largely due to the result of a
      twisted geometry of the alkoxide ion, stabilized by electrostatic interaction
      between the electronegative terminal O atom and a H atom on the gamma-carbon.
      These interactions are primarily due to internal rotation about the Calpha-Cbeta
      bonds for n-propoxide and the primary pentoxides.

PMID- 30232891
TI  - Zn(OAc)2-Catalyzed C3-Carbonylacetylation of Indoles with alpha-Diazoketones
      Involving Wolff Rearrangement.
AB  - Zn(OAc)2-catalyzed highly regioselective carbonylacetylation of indoles and
      pyrroles with alpha-diazoketones has been developed. This transformation involves
      a combination of Wolff rearrangement/cross-coupling relay and provides an
      efficient approach to versatile 3-carbonylacetylindoles and 2
      carbonylacetylpyrroles with a broad range of functional group tolerance.

PMID- 30232892
TI  - Combinatorial Enumeration of Isomers of Superaromatic Polysubstituted Cycloarenes
      and Coronoid Hydrocarbons with Applications to NMR.
AB  - We have employed combinatorial techniques based on character cycle indices,
      Polya's theory, and Euler totem function to enumerate isomers of polysubstituted
      cycloarenes and coronoid hydrocarbons which have been receiving considerable
      attention because of their superaromaticity, ring currents, and interesting
      magnetic properties. Systematic enumeration and construction of tables of
      polysubstituted isomers such as fluoro-chloro superaromatic hydrocarbons are
      considered as they are of interest in the study of environmental pollutants and
      toxicity. Isomers of fluoro-chloro polysubstituted donut shaped circumkekulenes,
      circumseptulenes, circumoctulenes, etc., are enumerated in addition to other
      cycloarenes, polycyclic circumcoronaphenes and coronoids. Applications to 13C
      NMR, proton NMR and multiple quantum NMR spectroscopies of these superaromatic
      species are considered.

PMID- 30232893
TI  - Palladium-Mediated Site-Selective C-H Radio-iodination.
AB  - The palladium-mediated C-H radio-iodination of arenes using sodium iodide as the
      primary isotopic source is reported and performed without chemical know-how in 30
      min and applied to the synthesis of complex radio-iodinated compounds of
      biological interest.

PMID- 30232894
TI  - Rhodium-Catalyzed Arylzincation of Alkynes: Ligand Control of 1,4-Migration
      Selectivity.
AB  - The addition of arylzinc reagents ArZnCl 1 to alkynes 2 was found to be catalyzed
      by rhodium complexes in the presence of a catalytic amount of zinc chloride. The
      selectivity in giving 2-arylalkenylzinc species 3 or ortho-alkenylarylzinc
      species 4, the latter of which is generated through 1,4-Rh migration from alkenyl
      to aryl in the catalytic cycle, is controlled by the ligands on rhodium. Ligands
      cod and binap gave 3 and 4, respectively, with high selectivity.

PMID- 30232895
TI  - Iridium-Catalyzed Unreactive C(sp3)-H Amination with 2,2,2
      Trichloroethoxycarbonyl Azide.
AB  - An additive-assisted iridium-catalyzed directed C(sp3)-H amination with 2,2,2
      trichloroethoxycarbonyl azide as an amino source is reported. Both carboxylate
      anions and the corresponding cations in the additives are crucial to achieve
      satisfactory efficiency. Sodium acetate or n-pentanoic acid can promote the
      amination of various primary C(sp3)-H bonds adjacent to secondary, tertiary, and
      quaternary carbons in ketoximes or N-aromatic heterocycles, respectively,
      providing a practical route to versatile beta-amino ketoxime and N-heteroaryl
      ethanamine derivatives. The amination products can be treated as isocyanate
      analogues and can be converted to other useful amino functionalities. An
      iridacyclic compound was isolated and identified as a plausible intermediate.

PMID- 30232896
TI  - Total Synthesis of Asperphenins A and B.
AB  - The first total synthesis of asperphenins A and B has been accomplished in a
      concise, highly stereoselective fashion from commercially available materials (15
      steps, 9.7% and 14.2% overall yields, respectively). The convergent route
      featured the judicious choice of protecting groups, fragment assembly strategy
      and a late-stage iron-catalyzed Wacker-type selective oxidation of an internal
      alkene to the corresponding ketone.

PMID- 30232898
TI  - Enantioselective and Divergent Syntheses of Alstoscholarisines A, E and Their
      Enantiomers.
AB  - Concise, enantioselective, and divergent syntheses of alstoscholarisines A and E
      are presented in 8 and 9 steps, respectively; alstoscholarisine E has never been
      accessed before. A boron-mediated aldol reaction and Rh-catalyzed
      cycloisomerization were exploited to access stereoisomers 8 and 9 as key
      intermediates. The challenging sterically congested alstoscholarisine core was
      furnished by a reductive transannular cyclization in the final steps. This
      strategy was also used for the syntheses of enantiomers of alstoscholarisines A
      and E.

PMID- 30232899
TI  - Hydroxyurea-Induced Oral Hyperpigmentation: A Case Report and Review of the
      Literature.

PMID- 30232897
TI  - Nanoscale Forces during Confined Cell Migration.
AB  - In vivo, immune cells migrate through a wide variety of tissues, including
      confined and constricting environments. Deciphering how cells apply forces when
      infiltrating narrow areas is a critical issue that requires innovative
      experimental procedures. To reveal the distribution and dynamics of the forces of
      cells migrating in confined environments, we designed a device combining
      microchannels of controlled dimensions with integrated deformable micropillars
      serving as sensors of nanoscale subcellular forces. First, a specific process
      composed of two steps of photolithography and dry etching was tuned to obtain
      micrometric pillars of controlled stiffness and dimensions inside microchannels.
      Second, an image-analysis workflow was developed to automatically evaluate the
      amplitude and direction of the forces applied on the micropillars by migrating
      cells. Using this workflow, we show that this microdevice is a sensor of forces
      with a limit of detection down to 64 pN. Third, by recording pillar movements
      during the migration of macrophages inside the confining microchannels, we reveal
      that macrophages bent the pillars with typical forces of 0.3 nN and applied
      higher forces at the cell edges than around their nuclei. When the degree of
      confinement was increased, we found that forces were redirected from inward to
      outward. By providing a microdevice that allows the analysis of force direction
      and force magnitude developed by confined cells, our work paves the way for
      investigating the mechanical behavior of cells migrating though 3D constricted
      environments.

PMID- 30232900
TI  - Predictive value of C-reactive protein after drug-eluting stent implantation: an
      update view.

PMID- 30232902
TI  - HPI Author Index.

PMID- 30232903
TI  - Editorial for HPI September Supplement.

PMID- 30232901
TI  - Clinical characteristics and survival in cardiogenic shock admissions to a UK
      heart transplant unit.
AB  - AIM: We describe the characteristics and outcomes of cardiogenic shock (CS)
      admissions to a UK transplant unit, which is previously unreported. PATIENTS &
      METHODS: Fifty-nine unselected, consecutive patients over a 38-month period in CS
      (INTERMACS <=2) and potentially eligible for transplant were retrospectively
      reviewed. RESULTS: Patients were predominantly male (76.3%), young (mean age 42.2
      years) and with severe end-organ dysfunction (acute liver/kidney injury 83%, mean
      lactate 3.5 mmol/l). 57.6% required mechanical support and 28.8% cardiac
      transplant. 30 days, discharge and 1-year survival were 78, 68 and 63%,
      respectively. Predictors of death included no transplant, increasing age and
      increasing creatinine. CONCLUSION: Patients with CS and potential for transplant
      require significant resource input but demonstrate favorable outcomes in our
      experience.

PMID- 30232904
TI  - Abstract book content list.

PMID- 30232905
TI  - A patient with multiple Swiss cheese aspect coronary lesions: optical coherence
      tomography to guide coronary angioplasty.
AB  - Although spontaneous recanalization of coronary thrombi has been reported
      pathologically, it is rarely recognized in clinical practice. We presented a rare
      case of recanalized thrombi of the right coronary artery and distal left anterior
      descending artery in a patient with an anterior ST segment elevation myocardial
      infarction treated with primary percutaneous intervention of the proximal left
      anterior descending artery. Optical coherence tomography aspect of right coronary
      artery was consistent with a 'Swiss cheese' appearance that represented
      recanalization of organized thrombi. Optical coherence tomography has been
      essential to discriminate the underlying mechanism and may provide useful
      information for an appropriate treatment approach.

PMID- 30232906
TI  - The cessation of oral anticoagulation following left atrial appendage surgery.
AB  - Atrial fibrillation is associated with a significantly increased risk of stroke,
      and oral anticoagulation is the mainstay of preventative treatment. Scenarios
      arise where the risks of treatment with oral anticoagulation may outweigh the
      benefits, most commonly when there is an elevated risk of bleeding. Studies of
      percutaneous closure of the left atrial appendage have strongly implicated this
      structure in the etiology of stroke in atrial fibrillation, and provide some
      rationale for the discontinuation of oral anticoagulation following percutaneous
      closure device implantation. A common clinical concern is the safety of cessation
      of oral anticoagulation after surgical closure of the left atrial appendage in
      patients with a history of atrial fibrillation. Here, we review the evidence
      guiding this management decision and draw comparison with data on percutaneous
      closure.

PMID- 30232907
TI  - Systemic immune response of gnotobiotic mice infected with porcine circovirus
      type 2 after administration of Lactobacillus reuteri L26 BiocenolTM.
AB  - In our previous study we confirmed an antiviral activity of probiotic
      Lactobacillus reuteri L26 which was mediated by stimulation of local intestinal
      immunity. The aim of this paper was to evaluate the influence of L. reuteri L26
      on the systemic immune response in gnotobiotic mice infected with porcine
      circovirus type 2 (PCV2). A total of 30 germ-free mice were divided into 3 groups
      and animals in noninfected and infected control groups (NC and IC; n=10) received
      sterile de Man-Rogosa-Sharpe broth for 7 days and animals in experimental group
      L+PCV (n=10) were inoculated with L. reuteri L26. Subsequently, mice in L+PCV and
      IC groups were infected with PCV2; however, mice in the control group received
      virus cultivation medium (mock). The results showed an increase of percentage of
      cytotoxic cells (CD8+ and CD49b+CD8-) and oxidative burst of phagocytes, up
      regulation of the gene expression of RANTES, granulocyte-macrophage colony
      stimulating factor, interferon-gamma and immunoglobulin A in blood above all in
      the later phase of infection (14 dpi) in L+PCV group accompanied by higher load
      of PCV2 in the serum. These findings indicate that L. reuteri L26 has a potential
      to induce systemic immune reaction, but in gnotobiotic mice immune stimulation
      can increase virus replication.

PMID- 30232908
TI  - The role of adjuvant probiotics to attenuate intestinal inflammatory responses
      due to cancer treatments.
AB  - Chemotherapy and radiotherapy treatment regimens for gastrointestinal, peritoneal
      and pelvic tumours can disrupt the intestinal microbiome and intestinal
      epithelia. Such disturbances can provoke symptoms such as diarrhoea, nausea and
      vomiting. Chemotherapy and radiotherapy induced gastrointestinal toxicity
      aggravating intestinal microbiome dysbiosis is postulated to adversely alter the
      intestinal microbiome, with a consequent induced pro-inflammatory effect that
      disrupts the intestinal microbiome-epithelia-mucosal immunity axis. Although not
      widely recognised, the intestinal mucosa is the largest and most densely and
      dynamically populated immune-environment. Cancer treatment adverse effects that
      affect intestinal and mucosal cells inadvertently target and disrupt resident
      intestinal macrophages, the cells that marshal immune activity in the intestinal
      mucosa by shaping pro-inflammatory and anti-inflammatory activities to control
      and eradicate infectious insults and maintain local homeostasis. Pathobionts
      (bacteria capable of pathogenic pro-inflammatory activity) and noxious
      environmental and bacterial antigens use the intestinal epithelia and gap
      junctions as a point of entry into the systemic circulation. This translocation
      movement promotes toxic sequelae that obstruct intestinal macrophage functions
      resulting in uncontrolled local and systemic pro-inflammatory activity, loss of
      phagocytic function and loss of expression of tight junction proteins. Probiotic
      bacteria as an adjunctive treatment shows efficacy in ameliorating enteropathies
      such as mucositis/diarrhoea resulting from chemotherapy or radiotherapy regimens.
      As such we posit that an important benefit that warrants a further focused
      research effort is the administration of adjuvant probiotics to help reduce the
      incidence of febrile neutropenia.

PMID- 30232909
TI  - Nomograms to predict survival rates for esophageal cancer patients with malignant
      behaviors based on ICD-0-3.
AB  - AIM: We aimed to investigate the effect of current treatment based on stage and
      histology type, which were important factors for treating esophageal cancer.
      METHODS: Log-rank test, COX and nomograms were used for survival analysis. DCA, C
      index and calibration curves were used for validation. RESULTS: A total of 3224
      patients were recruited. As for cT2-T4aM0 patients, chemotherapy and radiation
      prolonged overall survival (OS) for esophageal squamous cell carcinoma (ESCC) and
      chemotherapy improved OS for esophageal adenocarcinoma (EAC). Meanwhile,
      neoadjuvant radiotherapy had longer OS than adjuvant radiotherapy for ESCC. As
      for T4b patients, radiation and chemotherapy correlated with better OS for ESCC
      and chemotherapy prolonged OS for EAC. CONCLUSION: Neoadjuvant radiotherapy might
      be optimal for cT2-T4aM0 ESCC. Radiation was recommended for T4b ESCC while
      chemotherapy was recommended for T4b EAC.

PMID- 30232911
TI  - B-mode ultrasonographic evaluation of long bones in Falconiformes and
      Strigiformes birds.
AB  - Bone fractures in birds are usually diagnosed with the aid of traditional
      radiography. However, this technique remains limited because of the difficulties
      associating this examination with real-time procedures. The aim of this study was
      to describe the use of B-mode ultrasound to assess the long bones of two avian
      orders. For the study, we used carcases of birds from the orders Falconiformes (n
      = 9) and Strigiformes (n = 12), with weights ranging from 108 to 1020 g. An
      ultrasound device with a 5-12 MHz linear probe was employed to produce images of
      the long bones (humerus, radius, ulna, femur and tibiotarsus). Ultrasound (US)
      measurements and physical measurements using a caliper were applied to compare
      the diameter of the bones. Images were also recorded from the US examination
      performed in two live patients attending the hospital with suspected bone
      fractures. No statistical difference was found between the two methods of
      measurement in carcases weighing up to 267 g (P > 0.01). The US examination
      provided relevant clinical information about the bone cortex and assisted in real
      time surgical procedures. RESEARCH HIGHLIGHTS Long bones of Falconiformes and
      Strigiformes birds were assessed with B-mode ultrasound. Ultrasound analysis is a
      relevant tool in clinical orthopaedics for avian species. Ultrasound of the bone
      might be applied for monitoring of healing processes.

PMID- 30232910
TI  - Mobile health apps preferences and practice among ambulatory cardiovascular
      patients.
AB  - AIM: To determine if patients in cardiology practices would be interested in or
      willing to use mobile health technologies. METHODS: Patients seen at an
      ambulatory cardiology clinic for any indication were included. A paper survey was
      administered during pre-intake that assessed frequency of use, familiarity with
      and interest in mobile health applications. Data were analyzed using an
      exploratory logistic regression analysis to determine demographic predictors for
      technology utilization. RESULTS: A total of 306 patients were included (a
      plurality, 39.3%, in age group 50-69; 62.7% male). Those from median household
      incomes between US$30,000 and US$74,999 and those 18-29 years old were more
      likely to have used a health app (0.53 and 1.21, respectively). Those between 18
      and 29 years were less interested in virtual visits with their healthcare
      provider (-0.92) and those over age 70 were less comfortable using their phone
      apps (-0.80). CONCLUSION: Age and income are important predictors of mobile
      health app adoption.

PMID- 30232912
TI  - Quadrivalent human papilloma virus vaccine for the treatment of multiple warts: a
      retrospective analysis of 30 patients.
AB  - BACKGROUND: Various therapeutic modalities have been implemented for wart
      treatment, with limited efficacy. Recently, resistant warts treated using
      quadrivalent human papilloma virus (HPV) vaccine have been reported, although
      original articles on the efficacy of quadrivalent HPV vaccine on warts are rare.
      OBJECTIVE: We performed the present study to evaluate the efficacy of
      quadrivalent HPV vaccine in the treatment of multiple warts. METHODS: We
      retrospectively reviewed 30 patients from our centers. Patient demographics,
      clinical features such as duration of disease, number and location of lesions,
      therapeutic response, and adverse reactions were assessed. RESULTS: Regarding
      therapeutic response, 14 patients (46.67%) showed "Complete response", 5 (16.67%)
      showed "Partial response", and 11 (36.67%) showed "No response". There were no
      statistically significant differences in sex, age, disease duration, and lesion
      number and location between the three groups divided by treatment response. No
      severe adverse events after quadrivalent HPV vaccination were noted. CONCLUSION:
      The advantage of quadrivalent HPV vaccine in the treatment of warts is that it is
      more convenient and less painful. HPV vaccine might be a good alternative to
      conventional destructive methods for incompetent cases such as those including
      multiple warts, dangerous lesion locations, and uncooperative patients.

PMID- 30232913
TI  - Correlation of plasma microRNA-21 expression and bone turnover markers in
      postmenopausal women.
AB  - OBJECTIVES: This study assessed the correlation of plasma microRNA-21 expression
      and bone turnover markers (BTMs: CTx, P1NP) in healthy Thai postmenopausal women.
      We secondarily compared microRNA-21 expression between participants with normal
      and low bone mineral density (BMD: osteopenia and osteoporosis). METHODS:
      Postmenopausal women who had never been diagnosed with fracture or never used
      anti-osteoporosis drugs were included in this study. Baseline characteristics
      were collected from all 195 participants. BTMs and plasma miR-21-5p were analyzed
      from blood collection at 8:00 and 9:00 am after overnight fasting for at least 8
      h. RESULTS: There was no significant correlation between miR-21-5p and any of the
      BTMs (CTx, r = 0.094, p = 0.19; P1NP, r = 0.05, p = 0.485). Significant
      correlation between miR-21-5p and P1NP was found when participants were further
      categorized into those aged >=70 years (r = 0.46, p = 0.05) and those having
      osteoporosis (r = 0.51, p = 0.06). Slight negative correlations were found
      between miR-21-5p and BMD. There was statistically significant higher expression
      of miR-21-5p in those with low BMD when compared to the normal BMD group (p <
      0.01). CONCLUSION: In this study, we did not find significant correlation between
      plasma microRNA-21-5p expression and the BTMs. Nevertheless, there seemed to be
      higher expression of miR-21-5p in the low BMD participants.

PMID- 30232914
TI  - Effects of cyclic AMP on the differentiation and bioenergetics of rat C6 glioma
      cells.
AB  - INTRODUCTION: Elevation in the level of intracellular cAMP is known to induce
      astrocytic differentiation of C6 glioma cells by unknown mechanisms. METHODS:
      Therefore, cytoskeletal protein genes (phalloidin) fluorescents to investigate
      morphological changes, cell proliferation assay, MTT assay, flow cytometry,
      western blotting, in-cell western, immune-cytochemical (protein expression and
      localization), and oxygen electrodes (oxygen consumption rate) after a treatment
      with 0.25 mM dbcAMP were conducted. RESULTS: Undifferentiated cells (media
      without dbcAMP) showed a flat polygonal appearance, whereas those cultured in the
      presence of 0.25 mM dbcAMP exhibited a more differentiated astrocytic morphology.
      They had more numerous neurite-like thin processes. The cell proliferation of
      differentiated c6 glioma reduced at day 2 and then started to increase at day 3
      till day 5 compared to undifferentiated c6 glioma cells. In terms of flow
      cytometry data, dbcAMP had no apoptotic effect on the C6 glioma cells. There was
      an increase in the protein expression GFAP (specific marker for astrocytes).
      There was no significant effect between undifferentiated and 5-day
      differentiation regarding their response to glucose 10 mM. In addition, there
      were no significant effects of glucose on the basal of 5-day differentiation of
      C6 glioma cells. However, there was a significant correlation between the
      concentration of glucose and inhibition of the basal oxygen consumption. Finally,
      glucose 10 mM did not stimulate NAD (P)H levels of C6 glioma cells. CONCLUSION:
      The above results showed that cAMP induce C6 glioma cells differentiation without
      affecting its bioenergetics. Therefore cAMP is considered to be the best
      differentiating agent.

PMID- 30232915
TI  - RNAi-based therapeutics for lung cancer: biomarkers, microRNAs, and nanocarriers.
AB  - INTRODUCTION: Despite the current advances in the discovery of the lung cancer
      biomarkers and, consequently, in the diagnosis, this pathology continues to be
      the primary cause of cancer-related death worldwide. In most cases, the illness
      is diagnosed in an advanced stage, which limits the current treatment options
      available and reduces the survival rate. Therefore, RNAi-based therapy arises as
      a promising option to treat lung cancer. Areas covered: This review provides an
      overview on the exploitation of lung cancer biology to develop RNAi-based
      therapeutics to be applied in the treatment of lung cancer. Furthermore, the
      review analyzes the main nanocarriers designed to deliver RNAi molecules and
      induce antitumoral effects in lung cancer, and provides updated information about
      current RNAi-based therapeutics for lung cancer in clinical trials. Expert
      opinion: RNAi-based therapy uses nanocarriers to perform a targeted and efficient
      delivery of therapeutic genes into lung cancer cells, by taking advantage of the
      known biomarkers in lung cancer. These therapeutic genes are key regulatory
      molecules of crucial cellular pathways involved in cell proliferation, migration,
      and apoptosis. Thereby, the characteristics and functionalization of the
      nanocarrier and the knowledge of lung cancer biology have direct influence in
      improving the therapeutic effect of this therapy.

PMID- 30232916
TI  - Istradefylline for the treatment of Parkinson's disease: is it a promising
      strategy?
AB  - INTRODUCTION: Istradefylline (ISD) is a new drug developed for the treatment of
      Parkinson's disease (PD). It is an adenosine receptor A2A antagonists that will
      represent an important option for patients with advanced PD where it has been
      demonstrated efficacy in decreasing daily OFF time and is well tolerated. ISD has
      been marketed in Japan since May 2013. Areas covered: The objective of this
      review is to summarize evidences emerged from clinical studies that have
      demonstrated the efficacy of ISD in advanced parkinsonian patients. It will then
      focus on the potential role in treating non-motor symptoms (NMS) and cognitive
      decline, which heavily affect quality of life for PD patients. Its putative role
      as neuroprotective agent will also be discussed. Expert opinion: ISD might
      represent an alternative option for patients with advanced PD. The reduction of
      OFF time highlighted in pivotal trials is comparable to that obtained with
      different levodopa adjunct therapies. The low profile of side effects makes ISD a
      more suitable drug for advanced patients whose illness is complicated by
      depression or cognitive impairment. Future studies are warranted to investigate
      the possible effects of this drug to delay the occurrence of dyskinesia and to
      impact significantly on NMS.

PMID- 30232917
TI  - Giant left atrium with left lung damage: a case report.
AB  - Giant left atrium is most commonly associated with rheumatic mitral valve
      disease, causing a series of cardiac and extracardiac complications. Cardiac
      complications are often reported, such as atrial fibrillation, decreased cardiac
      output, and atrial thrombus formation. Extracardiac complications are rarely
      described in the literature. We report an unusual case of a 55-year-old woman who
      was diagnosed with rheumatic heart disease 20 years earlier. Her chief complaints
      were episodes of chest tightness and difficulty breathing, which she had for more
      than 30 years. Echocardiography showed severe mitral stenosis with severe mitral
      insufficiency. Contrast-enhanced chest CT showed that the left thoracic cavity
      was occupied by a giant left atrium. The left main bronchus was compressed, and
      the left lung showed complete consolidation without pulmonary function.

PMID- 30232918
TI  - A comparison of alternative access routes for transcatheter aortic valve
      implantation.
AB  - INTRODUCTION: Alternative transcatheter aortic valve implantation (TAVI)
      approaches offer the possibility of valve replacement in patients ineligible to
      the transfemoral route. Authors provide an updated review of the existing
      alternative approaches. Areas covered: A systematic review of alternative
      approaches for TAVI was undertaken. The feasibility, safety, efficacy, and
      technical requirements of the transapical, transaortic, transcarotid,
      transsubclavian, and transcaval approaches have been compared. A multislice
      computed tomography is often necessary for pre-operative planning. Although the
      first developed, the transapical pathway tends to be abandoned because of its
      high morbidity. Transaortic approach requires a mini-sternotomy or thoracotomy
      and general anesthesia limiting its' acceptance. Transcarotid approach requires a
      mini-invasive surgical cutdown but is feasible under conscious sedation. Registry
      data provided reassurance regarding the stroke risk with the transcarotid
      approach. Transsubclavian pathway is recent and feasible percutaneously although
      necessitates additional complex maneuvers to avoid serious bleeding
      complications, which extends its' learning curve. Transcaval approach is still
      experimental but may benefit from technological advances. Expert commentary: The
      choice of the alternative approach dependents on patient anatomy and
      comorbidities, and local operator expertise and skills. Transaortic, transcarotid
      and transsubclavian are nowadays used the most. However, comparative data to
      favor one approach over another is lacking and further research is warranted.

PMID- 30232919
TI  - Occipital lobe epilepsy was presented in a patient with intracerebral schwannoma:
      a case report and literature review.
AB  - Schwannoma arising within brain parenchyma is a rare scenario. So far, only 70
      cases were reported. We reported a case of intracerebral schwannoma presented
      with occipital lobe epilepsy, which has never been reported before. A 19-year-old
      man suffered from intermittent blurred vision and headache. Neuroradiological
      findings showed a left occipital lesion with cystic and solid components.
      Histological and electron micrograph features confirmed the diagnosis of
      schwannoma after the tumor was totally removed. The theories and literature
      related to this case were reviewed and the possible developmental origin was
      discussed. We found that this kind of schwannoma is more often in adolescent and
      young adults.

PMID- 30232920
TI  - Going meta on metacognitive interventions.

PMID- 30232921
TI  - An alternative approach to solving the opioid epidemic: is there a role for non
      pharmacologic analgesic therapies?

PMID- 30232922
TI  - Association of HTR1A gene polymorphisms with obsessive-compulsive disorder and
      its treatment response: the influence of sex and clinical characteristics.
AB  - OBJECTIVE: There have been controversial results in the literature on the
      association between HTR1A polymorphisms (rs10042486, C-1019G, and Gly272Asp) and
      obsessive-compulsive disorder (OCD). Here, the plausibility for such genetic and
      pharmacogenetic association was investigated by assessing a sample of Iranian OCD
      patients. METHOD: OCD patients had fulfilled the criteria for DSM-IV-TR with Y
      BOCS scores higher than 9. A total of 207 controls and 205 patients' blood
      samples were genotyped by means of PCR-RFLP. RESULTS: The results showed that
      there was no association between these three SNPs and the treatment response. The
      distribution of rs10042486 genotypes was significantly different in the patients
      compared to the controls. The association analyses of the C-1019G showed
      significant differences in the genotypic frequency of the patients with or
      without a positive family history of psychiatric disorders. Similar differences
      in female patients were also observed. We found that the age of onset also
      associates with the C-1019G polymorphism but only in the female patients. No
      association of Gly272Asp polymorphism and OCD was observed in this study.
      CONCLUSION: We concluded that among the HTR1A polymorphisms, only the association
      of rs10042486 CT genotype and OCD was statistically significant. The association
      of C-1019G with OCD by considering the age of onset and family history was just
      significant in the female patients. No significant association between the
      studied HTR1A SNPs with treatment response was observed. Acquiring both positive
      and negative pharmacogenetic outcomes in each population helps to select the
      appropriate medication for a particular patient with fewer side effects.

PMID- 30232923
TI  - A robust and powerful test for case-control genetic association study on X
      chromosome.
AB  - Hundreds of genome-wide association studies were conducted to map the disease
      genes on autosomes in human beings. It is known that many complex diseases are
      sex-determined and X chromosome is expected to play an important role. However,
      only a few single-nucleotide polymorphisms on X chromosome were found to be
      significantly associated with the diseases under study. On the other hand, to
      balance the genetic effect between two sexes, X chromosome inactivation occurs in
      most of X-linked genes by silencing one copy of two X chromosomes in females and
      dosage compensation is achieved. A few association studies on X chromosome
      incorporated the information on dosage compensation. However, some of them
      require the assumption of Hardy-Weinberg equilibrium and some need to specify the
      underlying genetic model. Therefore, in this article, we propose a novel method
      for association by taking account of different dosage compensation patterns. The
      proposed test is a robust approach because it requires neither specifying the
      underlying genetic models nor the assumption of Hardy-Weinberg equilibrium.
      Further, the proposed method allows for different deviations from Hardy-Weinberg
      equilibrium between cases and controls. Simulation results demonstrate that our
      proposed method generally outperforms the existing methods in terms of
      controlling the size and the test power. Finally, we apply the proposed test to
      the meta-analysis of the Graves' disease data for its practical use.

PMID- 30232924
TI  - A Corpus-Based Exploration of the Discourse Marker Well in Spoken Interlanguage.
AB  - This corpus-based study examines the widely-used discourse marker well in Chinese
      speaking learners' speech and compares its frequencies in native speaker data and
      Swedish learners. While Swedish learners overuse well, Chinese-speaking learners
      (predominantly at the upper-intermediate level) significantly underuse it. The
      positions and functions of well are further examined using a functional
      framework. One-fourth of the Chinese-speaking learners who use well manipulate
      its positions in utterances in a similar way to native speakers. In terms of
      functions, well is employed for speech management much more frequently than for
      attitudinal purposes. The greater use of the former does not generally create
      negative effects, but the under-representation of the latter may suggest that
      Chinese-speaking learners sound too direct in certain contexts. The paper
      concludes by considering pedagogical implications for different first languages
      and proficiency levels and their possible applications to the instruction of
      well.

PMID- 30232925
TI  - Heuristic Patterns of Ethical Decision Making.
AB  - This article describes the context of ethical decision making in research and
      suggests that direct attention to the ways in which decisions are actually made
      in such environments is needed. A decision-making model based on the literature
      on heuristic processing is proposed and is followed by a review of the method,
      data, and results of the authors' research on this model. The implications of the
      research are developed, and a research agenda is outlined. Key findings were that
      competent actors do indeed process ethics problems heuristically and in ways that
      interweave intuitive, affective, and more rational phases. This processing does
      not typically follow a simple progressive pattern but evidences a sort of trial
      and-error processing that is consistent with the logic of heuristic processing
      more generally. Finally, while diverse, participant-level processing attempts
      appear to follow patterns which are associated with the experience and training
      of the actors.

PMID- 30232926
TI  - Knowledge patterns for online health portal development.
AB  - This article describes the development and evaluation of a set of knowledge
      patterns that provide guidelines and implications of design for developers of
      mental health portals. The knowledge patterns were based on three foundations:
      (1) knowledge integration of language technology approaches; (2) experiments with
      language technology applications and (3) user studies of portal interaction. A
      mixed-methods approach was employed for the evaluation of the knowledge patterns:
      formative workshops with knowledge pattern experts and summative surveys with
      experts in specific domains. The formative evaluation improved the cohesion of
      the patterns. The results of the summative evaluation showed that the problems
      discussed in the patterns were relevant for the domain, and that the knowledge
      embedded was useful to solve them. Ten patterns out of thirteen achieved an
      average score above 4.0, which is a positive result that leads us to conclude
      that they can be used as guidelines for developing health portals.

PMID- 30232927
TI  - fMRI evidence supporting the role of memory conflict in the deja vu experience.
AB  - Attempts to generate deja vu experimentally have largely focused on engineering
      partial familiarity for stimuli, relying on an ensuing, but unprompted evaluation
      of conflict to generate the experience. Without verification that experimentally
      generated familiarity is accompanied by the awareness of stimulus novelty, these
      experimental procedures potentially provide an incomplete deja vu analogue. We
      used a modified version of the Deese-Roediger-McDermott (DRM) false memory
      procedure to generate both familiarity and novelty within a deja vu analogue - we
      coupled experimentally-generated familiarity with cues indicating that the
      familiarity was erroneous, using this additional source of mnemonic information
      to generate cognitive conflict in our participants. We collected fMRI and
      behavioural data from 21 participants, 16 of whom reported deja vu. Using
      univariate contrasts we identified brain regions associated with mnemonic
      conflict, including the anterior cingulate cortex, medial prefrontal cortex and
      parietal cortex. This is the first experiment to image an analogue of the deja vu
      experience in healthy volunteers. The increased likelihood of deja vu reports to
      DRM critical lures correctly identified as "new", and the activation of neural
      substrates supporting the experience of cognitive conflict during deja vu,
      suggest that the resolution of memory conflict may play an integral role in deja
      vu.

PMID- 30232928
TI  - Optimal designs for testing hypothesis in multiarm clinical trials.
AB  - The present paper deals with the problem of designing randomized multiarm
      clinical trials for treatment comparisons in order to achieve a suitable trade
      off among inferential precision and ethical concerns. Although the large majority
      of the literature is focused on the estimation of the treatment effects, in
      particular for the case of two treatments with binary outcomes, the present paper
      takes into account the inferential goal of maximizing the power of statistical
      tests to detect correct conclusions about the treatment effects for normally
      response trials. After discussing the allocation optimizing the power of the
      classical multivariate test of homogeneity, we suggest a multipurpose design
      methodology, based on constrained optimization, which maximizes the power of the
      test under a suitable ethical constraint reflecting the effectiveness of the
      treatments. The ensuing optimal allocation depends in general on the unknown
      model parameters but, contrary to the unconstrained optimal solution or to some
      targets proposed in the literature, it is a non-degenerate continuous function of
      the treatment contrasts, and therefore it can be approached by standard response
      adaptive randomization procedures. The properties of this constrained optimal
      allocation are described both theoretically and through suitable examples,
      showing good performances both in terms of ethical gain and statistical
      efficiency, taking into account estimation precision as well.

PMID- 30232929
TI  - Manual laterality in marsupials.

PMID- 30232930
TI  - Surgical incision induces learning impairment in mice partially through
      inhibition of the brain-derived neurotrophic factor signaling pathway in the
      hippocampus and amygdala.
AB  - Surgical incision-induced nociception contributes to the occurrence of
      postoperative cognitive dysfunction. However, the exact mechanisms involved
      remain unclear. Brain-derived neurotrophic factor (BDNF) has been demonstrated to
      improve fear learning ability. In addition, BDNF expression is influenced by the
      peripheral nociceptive stimulation. Therefore, we hypothesized that surgical
      incision-induced nociception may cause learning impairment by inhibiting the
      BDNF/tropomyosin-related kinase B (TrkB) signaling pathway. The fear conditioning
      test, enzyme-linked immunosorbent assay, and Western blot analyses were used to
      confirm our hypothesis and determine the effect of a plantar incision on the fear
      learning and the BDNF/TrkB signaling pathway in the hippocampus and amygdala. The
      freezing times in the context test and the tone test were decreased after the
      plantar incision. A eutectic mixture of local anesthetics attenuated plantar
      incision-induced postoperative pain and fear learning impairment. ANA-12, a
      selective TrkB antagonist, abolished the improvement in fear learning and the
      activation of the BDNF signaling pathway induced by eutectic mixture of local
      anesthetics. Based on these results, surgical incision-induced postoperative
      pain, which was attenuated by postoperative analgesia, caused learning impairment
      in mice partially by inhibiting the BDNF signaling pathway. These findings
      provide insights into the mechanism underlying surgical incision-induced
      postoperative cognitive function impairment.

PMID- 30232932
TI  - Predicting parkinsonism side-effects of antipsychotic polypharmacy prescribed in
      secondary mental healthcare.
AB  - BACKGROUND:: Computer-modelling approaches have the potential to predict the
      interactions between different antipsychotics and provide guidance for
      polypharmacy. AIMS:: To evaluate the accuracy of the quantitative systems
      pharmacology platform to predict parkinsonism side-effects in patients prescribed
      antipsychotic polypharmacy. METHODS:: Using anonymized data from South London and
      Maudsley NHS Foundation Trust electronic health records we applied quantitative
      systems pharmacology, a neurophysiology-based computer model of humanized
      neuronal circuits, to predict the risk for parkinsonism symptoms in patients with
      schizophrenia prescribed two concomitant antipsychotics. The performance of the
      quantitative systems pharmacology model was compared with the performance of
      simple parameters such as: combination of affinity constants (1/Ksum); sum of D2R
      occupancies (D2R) and chlorpromazine equivalent dose. RESULTS:: We identified 832
      patients with schizophrenia who were receiving two antipsychotics for six or more
      months, between 1 January 2007 and 31 December 2014. The area under the receiver
      operating characteristic (AUROC) curve for the quantitative systems pharmacology
      model was 0.66 ( p = 0.01), while AUROCs for D2R, 1/Ksum and chlorpromazine
      equivalent dose were 0.52 ( p = 0.350), 0.53 ( p = 0.347) and 0.52 ( p = 0.330)
      respectively. CONCLUSION:: Our results indicate that quantitative systems
      pharmacology has the potential to predict the risk of parkinsonism associated
      with antipsychotic polypharmacy from minimal source information, and thus might
      have potential decision-support applicability in clinical settings.

PMID- 30232931
TI  - Cell type-specific DNA methylation in neonatal cord tissue and cord blood: a 850K
      reference panel and comparison of cell types.
AB  - Accounting for cellular heterogeneity is essential in neonatal epigenome-wide
      association studies (EWAS) performed on heterogeneous tissues, such as umbilical
      cord tissue (CT) or cord blood (CB). Using a reference-panel-based statistical
      approach, the cell type composition of heterogeneous tissues can be estimated by
      comparison of whole tissue DNA methylation profiles with cell type-specific DNA
      methylation signatures. Currently, there is no adequate DNA methylation reference
      panel for CT, and existing CB panels have been generated on lower coverage
      Infinium HumanMethylation450 arrays. In this study, we generate a reference panel
      for CT and improve available CB panels by using the higher coverage Infinium
      MethylationEPIC arrays. We performed DNA methylation profiling of 9 cell types
      isolated from CT and CB samples from 14 neonates. In addition to these cell
      types, we profiled DNA methylation of unfractionated CT and CB. Cell type
      composition of these unfractionated tissue samples, as estimated by our reference
      panels, was in agreement with that obtained by flow cytometry. Expectedly, DNA
      methylation profiles from CT and CB were distinct, reflecting their mesenchymal
      and hematopoietic stem cell origins. Variable CpGs from both unfractionated CT
      and its isolated cell types were more likely to be located in open seas and
      intronic regions than those in CB. Cell type specific CpGs in CT were enriched in
      intercellular matrix pathways, while those from CB were enriched in immune
      related pathways. This study provides an open source reference panel for
      estimation and adjustment of cellular heterogeneity in CT and CB, and broadens
      the scope of tissue utilization assessed in future neonatal EWAS studies.

PMID- 30232934
TI  - Healthcare reform, quality and safety perspectives, participants, partnerships
      and prospects in 30 countries.

PMID- 30232933
TI  - Non-interventional study of the safety and effectiveness of fluticasone
      propionate/formoterol fumarate in real-world asthma management.
AB  - INTRODUCTION: In recognition of the value of long-term real-world data, a
      postauthorization safety study of the inhaled corticosteroid (ICS) fluticasone
      propionate and long-acting beta2-agonist (LABA) formoterol fumarate
      (fluticasone/formoterol; Flutiform(r)) was conducted. METHODS: This was a 12
      month observational study of outpatients with asthma aged ? 12 years in eight
      European countries. Patients were prescribed fluticasone/formoterol according to
      the licensed indication, and independently of their subsequent enrolment in the
      study. They were then treated according to local standard practice. The study
      objectives were to evaluate the safety and effectiveness of
      fluticasone/formoterol under real-world conditions. RESULTS: The safety
      population for this study comprised 2539 patients (mean age 47.7 years; 94.3%
      aged ? 18 years; 63.4% female). Most patients (1538/2539, 60.6%) had switched to
      fluticasone/formoterol from another ICS/LABA, primarily due to lack of efficacy
      (1150/2539, 45.3%). Three quarters (77.4%) of patients were treated for 12
      months, and 80.6% continued fluticasone/formoterol treatment after the study.
      Adverse events (AEs) occurred in 60.0% patients, and 10.2% had AEs considered
      possibly related to fluticasone/formoterol [most commonly asthma exacerbation
      (2.0% patients), dysphonia (1.8%) and cough (1.1%)]. Thirty-six severe AEs, but
      no serious AEs, were considered possibly related to fluticasone/formoterol. The
      proportion of patients with controlled asthma (based on Asthma Control Test score
      ? 20) increased from 29.4% at baseline to 67.4% at study end (last observation
      carried forward). The proportion of patients experiencing at least one severe
      exacerbation decreased from 35.8% in the year prior to enrolment to 9.8% during
      the study. Improvements from baseline to study end were also observed in Asthma
      Quality of Life scores and physician/patient reports of satisfaction with
      treatment. CONCLUSION: In this real-world postauthorization safety study,
      fluticasone/formoterol demonstrated a safety profile consistent with that seen in
      controlled clinical trials, with effectiveness in improving asthma control.

PMID- 30232935
TI  - Cochlear implant in Thalassemia patient - Case report.
AB  - INTRODUCTION: Beta-thalassemias are a group of hereditary blood disorders
      characterized by anomalies in the synthesis of the beta chains of hemoglobin.
      Iron overload occurs in thalassemia, with blood transfusion therapy being the
      major cause. Deferoxamine continues to be the mainstay of therapy to remove
      excess iron in patients requiring long-term transfusions. One of the most
      important complications of deferoxamine therapy is neurosensory toxicity,
      including sensorineural hearing loss (SNHL). Labyrinthine hemmorhage (LH) is
      thought to result from altered capillary hemodynamics or reperfusion injury. It
      is theorized that LH incites a reparative response that cascades from fibrosis to
      sclerosis and ultimately ossification of the inner ear structures. CASE
      PRESENTATION: We present a case of 3-year-old thalassemic child with bilateral
      profound sensorineural hearing loss. Patient was on regular blood transfusions
      with chelation therapy. HRCT temporal bone and MRI brain and temporal bone had
      features of labyrinthitis ossificans (LO). Child underwent uniateral cochlear
      implantation and postimplantation speech perception and production outcomes were
      normal. DISCUSSION: This case illustrates the unique feature of labyrinthitis
      ossificans in a thalassemia patient which has not yet reported in the English
      literature. Hearing screening of all thalassemia patients and therefore early
      diagnosis of SNHL prompts early intervention and improved quality of life.

PMID- 30232936
TI  - Re-Watching Lectures as a Study Strategy and Its Effect on Mind Wandering.
AB  - Material re-exposure (e.g., re-reading) is a popular mnemonic strategy, however,
      its utility has been questioned. We extend research on re-reading to re-watching 
      an emerging mnemonic technique given the increased use of recorded lectures
      today (e.g., in online courses). Consistent with findings from recent
      investigations of re-reading, there were no benefits of massed re-watching on
      memory for lecture material and re-watching increased rates of mind wandering. We
      discuss implications for understanding the cognitive consequences of re-exposure
      based mnemonics.

PMID- 30232937
TI  - Response Preparation With Reliable Cues Decreases Response Competition in the
      Flanker Task.
AB  - We tested the hypothesis that selective response preparation, based on reliable
      response cues, reduces response conflict in an Eriksen flanker task. Previous
      studies of this issue produced inconclusive results because presenting an always
      valid response cue before the stimulus display turns a choice-response task into
      a simple-response task, in which full processing of the actual stimulus display
      is no longer necessary. We conducted two experiments in which we matched stimulus
      processing in conditions without cues and with reliable cues as far as possible.
      In both experiments, we presented a nogo target stimulus in 25% of the trials.
      The different cueing conditions were presented in separate blocks in Experiment 1
      but mixed within blocks in Experiment 2. The most important result was the
      reduction of response conflict as induced by incompatible flanker stimuli in both
      experiments with reliable response cues. This finding supports the notion of a
      negative preparation-interference relationship.

PMID- 30232938
TI  - When a Reactivated Visual Mask Disrupts Serial Recall.
AB  - To prevent forgetting in working memory, the attentional refreshing is supposed
      to increase the level of activation of memory traces by focusing attention.
      However, the involvement of memory traces reactivation in refreshing relies in
      the majority on indirect evidence. The aim of this study was to show that
      refreshing relies on the reactivation of memory traces by investigating how the
      reactivation of an irrelevant trace prevents the attentional refreshing to take
      place, and (2) the memory traces reactivated are sensorial in nature. We used a
      reactivated visual mask presented during the encoding (Experiment 1) and the
      refreshing (Experiment 2) of pictures in a complex span task. Results showed
      impaired serial recall performance in both experiments when the mask was
      reactivated compared to a control stimulus. Experiment 3 confirmed the refreshing
      account of these results. We proposed that refreshing relies on the reactivation
      of sensory memory traces.

PMID- 30232939
TI  - What Is Transferred in Causal Generalization Across Contexts?
AB  - The covariation and causal power account for causal induction make different
      predictions for what is transferred in causal generalization across contexts. Two
      experiments tested these predictions using hypothetical scenarios in which the
      effect of an intervention was evaluated between (Experiment 1) or within
      (Experiment 2) groups. Each experiment contained a manipulation of DeltaP, power
      and their combination. Both experiments found that causal transfer was determined
      by DeltaP rather than causal power. The overall transfer pattern supports DeltaP
      transfer account rather than the other transfer accounts. Causal transfers based
      on DeltaP are irrational, violating the coherence criterion of the causal power
      framework. The DeltaP transfer is consistent with previous findings that DeltaP
      is a main mental non-normative measure of causal strength in causal induction.

PMID- 30232940
TI  - Polyvascular disease and risk: When two is not better than one.

PMID- 30232941
TI  - Life Sciences Discovery and Technology Highlights.

PMID- 30232942
TI  - The Internet of Things Is Digitizing and Transforming Science.
AB  - Over the past decade, cloud software has transformed numerous industries-from
      finance to logistics, marketing to manufacturing. The simplified aggregation of
      data, enabled by cloud computing, empowers individuals to glean insights and make
      data-driven decisions rapidly. In science, however, such a transformation has yet
      to emerge. The domain lacks centralized, machine-readable repositories of
      scientific data; this absence inhibits analytics and expedient decision-making.
      Recently, the Internet of Things (IoT) has served as a catalyst for digitizing
      and automating science. IoT enables the centralized collection and analysis of
      scientific data (e.g., instruments, sensors, and environments). Here, we discuss
      this new technology trend, its applications in laboratories and promise as a
      platform for improved efficiency, more innovative capabilities, and machine
      learning/artificial intelligence.

PMID- 30232943
TI  - The Internet of Things in the Life Sciences Laboratory.

PMID- 30232944
TI  - ?

PMID- 30232945
TI  - ?

PMID- 30232947
TI  - ?

PMID- 30232946
TI  - ?

PMID- 30232948
TI  - Core psychopathology of treatment-seeking patients with binge-eating disorder: a
      network analysis investigation.
AB  - BACKGROUND: Mental disorders may emerge as the result of interactions between
      observable symptoms. Such interactions can be analyzed using network analysis.
      Several recent studies have used network analysis to examine eating disorders,
      indicating a core role of overvaluation of weight and shape. However, no studies
      to date have applied network models to binge-eating disorder (BED), the most
      prevalent eating disorder. METHODS: We constructed a cross-sectional graphical
      LASSO network in a sample of 788 individuals with BED. Symptoms were assessed
      using the Eating Disorders Examination Interview. We identified core symptoms of
      BED using expected influence centrality. RESULTS: Overvaluation of shape emerged
      as the symptom with the highest centrality. Dissatisfaction with weight and
      overvaluation of weight also emerged as highly central symptoms. On the other
      hand, behavioral symptoms such as binge eating, eating in secret, and dietary
      restraint/restriction were less central. The network was stable, allowing for
      reliable interpretations (centrality stability coefficient = 0.74). CONCLUSIONS:
      Overvaluation of shape and weight emerged as core symptoms of BED. This trend is
      consistent with past network analyses of eating disorders more broadly, as well
      as literature that suggests a primary role of shape and weight concerns in BED.
      Although DSM-5 diagnostic criteria for BED does not currently include a cognitive
      criterion related to body image or shape/weight overvaluation, our results
      provide support for including shape/weight overvaluation as a diagnostic
      specifier.

PMID- 30232949
TI  - The ineffectiveness of applying moisture to the ear on the incidence and severity
      of otic barotrauma for air passengers.
AB  - OBJECTIVE: The application of moisture to the ear is anecdotally claimed to
      relieve the pain from otic barotrauma that can arise during aircraft descent.
      This claim was tested in a randomised double-blind study on an aircraft with
      eight participants heavily predisposed to barotrauma. METHODS: On the outward
      flight, half the participants wore 'active' devices that applied moisture to the
      external ear; the remainder wore placebo devices that contained no moisture, but
      were otherwise identical. On the return flight, the groups were reversed.
      Participants wore the devices from just before descent until landing, unless they
      experienced symptoms of barotrauma, in which case they switched to what they knew
      was an active device. RESULTS: There were no significant differences between
      conditions regarding the appearance of the tympanic membrane on landing or the
      discomfort levels immediately before and after any switch. CONCLUSION: Applying
      moisture is ineffective for passengers heavily predisposed to otic barotrauma.

PMID- 30232950
TI  - Childhood maltreatment and adult medical morbidity in mood disorders: comparison
      of unipolar depression with bipolar disorder.
AB  - BACKGROUND: The medical burden in mood disorders is high; various factors are
      thought to drive this pattern. Little research has examined the role of childhood
      maltreatment and its effects on medical morbidity in adulthood among people with
      unipolar depression and bipolar disorder.AimsThis is the first study to explore
      the association between childhood maltreatment and medical morbidity in bipolar
      disorder and in unipolar depression, and examine whether the impact of abuse and
      neglect are distinct or combined. METHOD: The participants consisted of 354
      psychiatrically healthy controls, 248 participants with recurrent unipolar
      depression and 72 with bipolar disorder. Participants completed the Childhood
      Trauma Questionnaire and received a validated medical history interview. RESULTS:
      Any type of childhood maltreatment, child abuse and child neglect were
      significantly associated with the medical burden in bipolar disorder, but not
      unipolar depression or for controls. These associations worked in a dose-response
      fashion where participants with bipolar disorder with a history of two or more
      types of childhood maltreatment had the highest odds of having a medical illness
      relative to those without such history or those who reported one form. No such
      significant dose-response patterns were detected for participants with unipolar
      depression or controls. CONCLUSIONS: These findings suggest that childhood
      maltreatment may play a stronger role in the development of medical illnesses in
      individuals with bipolar disorder relative to those with unipolar depression.
      Individuals who had been maltreated with a mood disorder, especially bipolar
      disorder may benefit most from prevention and intervention efforts surrounding
      physical health.Declaration of interestNone.

PMID- 30232951
TI  - The practicalities and barriers of using TEG6s in code red traumas: an
      observational study in one London major trauma centre.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Thromboelastography (TEG) can
      identify trauma-induced coagulopathy and guide blood product management. What did
      this study ask? What currently limits the utilization of TEG in one major trauma
      centre, and can it be used practically? What did this study find? TEG can be
      successfully run during a major trauma, but a lack of knowledge relating to
      interpretation hinders its impact on blood component management. Why does this
      study matter to clinicians? Prior to introducing point-of-care tests, e.g., TEG,
      education of staff is required to ensure it is optimally utilized.

PMID- 30232952
TI  - Fluctuation of pre-hemodialysis serum sodium?.
AB  - INTRODUCTION: Low pre-hemodialysis (pre-HD) serum sodium or hyponatremia is
      associated with higher mortality. Pre-HD serum sodium can be more stable over
      time with low fluctuation compared to other serum parameters. MATERIALS AND
      METHODS: We examined variation of pre-HD serum sodium in 24 months and after this
      point examined all-cause mortality in a cohort of 261 patients followed-up for
      48.8 (standard deviation (SD) = 19.1) months. 6,221 determinations of pre-HD
      serum sodium were made and corrected for glucose concentrations. Serum sodium was
      measured pre-HD monthly, and the variability was calculated using the coefficient
      of variation (CV). RESULTS: The mean age was of 60 +/- 14.1 years, 60.9% were
      men, 48% had diabetes mellitus, and diabetic nephropathy was the most frequent
      cause of end-stage renal disease. Median CV of sodium in 24 months was 1.7% with
      a mean of 1.78% (95% CI 1.73 - 1.83). Patients with CV > 1.7% had a higher
      mortality (53 patients a 36.8%) compared to CV < 1.7% (22 patients a 18.8%) (p =
      0.002). In Kaplan-Meier analysis, patients with CV > 1.7% had significantly worse
      overall survival (log rank = 6.395, p = 0.011). We also stratified the sample in
      serum sodium tertiles (< 138 mEq/L; 138 - 140 mEq/L; > 140 mEq/L) and made a
      Kaplan-Meier analysis which showed persistent worse survival outcomes in patients
      with CV > 1.7% (log rank Mantel-Cox 7.64; p = 0.006). Cox regression multivariate
      model showed that CV of sodium was significantly associated with overall
      mortality after adjusting for confounder variables (hazard ratio 2.16, 95% CI
      1.37 - 3.41; p = 0.001). CONCLUSION: Variation of pre-HD serum sodium in 2 years
      is less than a 2%. With the limitations of our study, a higher variability of pre
      HD serum sodium in 2 years of treatment (CV > 1.7%) is associated with increased
      mortality.?.

PMID- 30232953
TI  - Hepatitis E infection in solid organ transplant recipients: An overlooked
      diagnosis??.
AB  - Hepatitis E virus (HEV) is gaining recognition as an important but under
      recognized pathogen, particularly in immunocompromised individuals. It should be
      considered as a potential differential diagnosis in such patients presenting with
      acute hepatitis. We report a case of a kidney-pancreas transplant recipient who
      developed acute liver dysfunction; this was found to be due to HEV infection
      acquired through consumption of undercooked pork. His immunosuppression was
      cautiously reduced, and his liver biochemistry and viral PCR gradually normalized
      without the need for additional antiviral therapy.?.

PMID- 30232954
TI  - Community acute kidney injury is associated with short- and long-term adverse
      outcomes in patients admitted with acute myocardial infarction?.
AB  - AIMS: The influence of community acute kidney injury on patients with myocardial
      infarction has not been explored. The Veterans Affair electronic health system
      was analyzed to test the hypothesis that patients who have myocardial infarction
      complicated by community acute kidney injury have higher short- and long-term
      mortality and cardiovascular outcomes than those who do not suffer acute kidney
      injury. MATERIALS AND METHODS: Odd ratios were calculated for in-hospital
      mortality. Cox proportional hazard model was used to assess hazard ratios for
      long-term mortality comparing patients with and without community acute kidney
      injury. Secondary outcomes included recurrent cardiovascular events including
      hospitalization for congestive heart failure, stroke, or repeat myocardial
      infarction. RESULTS: 10,689 patients were available for evaluation, 679 had
      community acute kidney injury and 10,010 with no acute kidney injury. Community
      acute kidney injury resulted in higher odds for inpatient mortality (odds ratio
      5.87, p < 0.001), and adjusted hazard ratio for mortality at 5 years as compared
      to no acute kidney injury (hazard ratio 1.67, p < 0.001). No differences in
      cardiovascular outcomes were identified in Cox proportional hazard analysis.
      CONCLUSION: In patients with myocardial infarction, community acute kidney injury
      is associated with delays in or not receiving appropriate myocardial infarction
      related process of care measures. In addition it is an independent predictor of
      short- and long-term mortality.?.

PMID- 30232955
TI  - Synaptic plexi of U-fibre layer beneath focal cortical dysplasias: Role in
      epileptic networks.
AB  - AIMS: The purpose is to demonstrate heterotopic neurones and their synaptic plexi
      within the U-fibre layer beneath focal cortical dysplasias (FCD). MATERIALS AND
      METHODS: This prospective qualitative neuropathological study included 23
      patients, ages from 3 months to 17 years: resections at epileptogenic foci in 10
      FCD Ia; 6 FCD IIa,b; 2 FCD IIIa,d; 3 HME; 2 TSC; 8 controls. TECHNIQUES:
      immunoreactivities for synaptophysin, NeuN, MAP2, SMI32, calretinin, GFAP,
      vimentin, alpha-B-crystallin. Bielschowsky silver; LFB; mitochondrial enzyme
      histochemistry (frozen sections). RESULTS: Subcortical white matter in FCD
      exhibited neuronal dispersion within U-fibres in FCD I, II and also deep white
      matter neuronal clusters in FCD II, HME, TSC. Neurones reacted for NeuN, MAP2;
      few for calretinin. Synaptophysin well demonstrated elaborate U-fibre plexi
      including axones between U-fibre neurones and projecting to overlying cortex.
      Deep white matter axones interconnected heterotopia but did not penetrate U
      fibres to reach cortex. Mitochondrial enzymatic activity was intense in some
      neurones, normal in others. Glial alpha-B-crystallin served as a marker of
      epileptogenic zones identified electrographically. CONCLUSION: U-fibre synaptic
      plexi contribute to excitatory circuitry in the cortex and thus to epileptic
      networks. Deep white matter neurones form local, less integrated plexi except
      transmantle dysplasias continuous with cortex. U-fibres may be a barrier to
      axonal penetration from deep heterotopia. Hypermetabolic neurones suggest
      repetitive ictogenic depolarizations. Gyral resections should include the U-fibre
      layer. Neuropathology reports should describe subcortical plexi. Synaptophysin
      immunoreactivity is a valuable supplement for this purpose.?.

PMID- 30232956
TI  - A rare case of osteochondroma of the coccyx.

PMID- 30232957
TI  - NSAIDs may prevent EGFR-TKI-related skin rash in non-small cell lung cancer
      patients?.
AB  - OBJECTIVES: Skin rash is a common adverse event induced by epidermal growth
      factor receptor tyrosine kinase inhibitors (EGFR-TKI). Here, we aimed to predict
      factors that reduce EGFR-TKI-related skin rash. MATERIALS AND METHODS: We
      conducted a single-center, retrospective study to predict factors that reduce
      skin rash in patients undergoing treatment for non-small cell lung cancer (NSCLC)
      with EGFR-TKIs using Cox proportional hazards model. RESULTS: Cox proportional
      hazard analysis revealed that coadministration of non-steroidal anti-inflammatory
      drug (NSAID) had protective effects against rash. Steroid coadministration showed
      a trend to being effective in reducing rash. CONCLUSION: NSAIDs may be useful in
      preventing EGFR-TKI-related skin rash.?.

PMID- 30232958
TI  - Pharmacokinetics and safety of salbutamol/ambroxol fixed-dose combination
      granules in healthy Chinese subjects?.
AB  - OBJECTIVES: The aim of the study was to investigate the pharmacokinetics and
      tolerability of salbutamol/ambroxol fixed-dose combination granules following
      single and multiple dosing in healthy Chinese subjects. MATERIALS AND METHODS:
      This was a randomized, open-label, two-period, one-sequence study (n = 12). Each
      subject received a single oral dose in period 1 and multiple doses in period 2.
      Plasma concentrations of these two components were determined using a validated
      LC-MS/MS method. Adverse events (AEs) were documented throughout the study.
      Investigators evaluated AEs in terms of frequency, duration, intensity,
      seriousness, outcome, and relationship to study drugs. RESULTS: Following single
      dosing, Cmax values were 8.07 +/- 1.31 ng/mL and 25.7 +/- 6.5 ng/mL for
      salbutamol and ambroxol, respectively. The corresponding T1/2 values were 8.15 +/
      3.13 hours and 9.31 +/- 2.27 hours, respectively. Moreover, no statistical
      differences in the pharmacokinetics of salbutamol and ambroxol in subjects
      receiving single or multiple dosage were observed. Single- and multiple-dose oral
      administration of fixed-dose combination granules were safe and well tolerated in
      healthy Chinese subjects. Drug hypersensitivity syndrome did not occur during our
      study. CONCLUSION: The pharmacokinetics of salbutamol and ambroxol in the fixed
      dose combination granules were not affected by dosing duration, and gender
      differences seemed to have no effect on the pharmacokinetics of salbutamol and
      ambroxol after a single dose and multiple doses of the medication.?.

PMID- 30232959
TI  - A rare case of diffuse intracranial aspergillosis masquerading as skull base
      meningioma in an immunocompetent patient.
AB  - Intracranial aspergillosis is rare in immunocompetent patients. Its presentation
      is subtle, often without any diagnostic characteristics, and is frequently
      mistaken for tuberculous meningitis, pyogenic abscess, or a space-occupying
      lesion. The authors report a case of diffuse intracranial aspergillosis, in an
      immunocompetent 34-year-old male, that mimicked a meningioma on preoperative
      imaging. The origin, clinical course, radiological features, histopathological
      findings, and surgical treatment are discussed based on review of literature.?.

PMID- 30232960
TI  - Making better sense of quantum mechanics.
AB  - We still lack any consensus about what one is actually talking about as one uses
      quantum mechanics. There is a gap between the abstract terms in which the theory
      is couched and the phenomena the theory enables each of us to account for so
      well. Because it has no practical consequences for how we each use quantum
      mechanics to deal with physical problems, this cognitive dissonance has managed
      to coexist with the quantum theory from the very beginning. The absence of
      conceptual clarity for almost a century suggests that the problem might lie in
      some implicit misconceptions about the nature of scientific explanation that are
      deeply held by virtually all physicists, but are rarely explicitly acknowledged.
      I describe here such unvoiced but widely shared assumptions. Rejecting them
      clarifies and unifies a range of obscure remarks about quantum mechanics made
      almost from the beginning by some of the giants of physics, many of whom are held
      to be in deep disagreement. This new view of physics requires physicists to think
      about science in an unfamiliar way. My primary purpose is to explain the new
      perspective and urge that it be taken seriously. My secondary aims are to explain
      why this perspective differs significantly from what Bohr, Heisenberg, and Pauli
      had been saying from the very beginning, and why it is not solipsism, as some
      have maintained. To emphasize that this is a general view of science, and not
      just of quantum mechanics, I apply it to a long-standing puzzle in classical
      physics: the apparent inability of physics to give any meaning to 'Now'-the
      present moment.

PMID- 30232961
TI  - UV-induced formation of oxygen-derived dangling bonds on hydroxyl-terminated SiC.
AB  - A combined theoretical and multi-technique experimental study was employed to
      comprehensively determine the electronic structure of 6H-SiC(0 0 0 1) surfaces
      upon hydroxyl and oxygen termination. We demonstrate the UV-induced formation of
      single-coordinated oxygen radicals in on-top sites above the atoms of the
      uppermost silicon layer of the substrate on initially hydroxyl-terminated SiC.
      Such a configuration of oxygen radicals represents an unprecedented adsorbate
      derived system of unpaired electrons, bearing analogy to silicon and carbon
      dangling bonds on clean, unreconstructed SiC surfaces. We evidence the presence
      of adsorbate-derived surface states within the fundamental band gap for both
      hydroxyl- and oxygen-terminated SiC. For hydroxyl termination, a hydrogen-induced
      unoccupied surface state is revealed consistently by inverse photoemission
      spectroscopy and density-functional theory calculations employing self
      interaction-corrected pseudopotentials (DFT-SIC). The formation of oxygen
      dangling bonds is accompanied by the occurrence of an occupied surface state
      derived from p x - and p y -orbitals associated with the unpaired electrons as
      proven by both ultraviolet photoemission spectroscopy and DFT-SIC.

PMID- 30232962
TI  - Leadership in public health.

PMID- 30232963
TI  - Universal health coverage in India: Newer innovations and the role of public
      health.
AB  - The realization of Universal Health Coverage requires adequate healthcare
      financing and human resources to provide financial protection to the economically
      disadvantaged population by covering their medicine, diagnostics, and service
      costs. Conventionally, inadequate public healthcare financing and the lack of
      skilled human resources are considered as the major barriers towards achieving
      UHC in India. To strengthen the Indian healthcare system, there has been
      significant increase budgetary allocation towards healthcare, a national health
      protection scheme targeting low-income households, upgrading of primary health
      care and expansion of the health work-force. Nevertheless, an evolving paradigm
      for improving holistic health, sanitation, nutrition, gender equity, drug
      accessibility and affordability, innovative initiatives in national health
      programs for reduction of maternal deaths, tuberculosis and HIV burden and the
      utilization of information technology in healthcare provision of the underserved
      and the marginalized is gaining rapid acceleration. These represent a genuine
      innovation towards fulfillment of UHC goals for India.

PMID- 30232964
TI  - Public health leadership in India: Reflections from my journey.
AB  - Public Health discipline has evolved and currently focuses on addressing social
      determinants of health and working multi-sectorally to promote health. Public
      Health Leadershipis the practice of mobilizing people, organizations, and
      communities to effectively tackle tough public health challenges. Leadership is a
      core competency of public health.Leaders are people with Vision, Influence,
      Values and Passion to achieve personal and organizational mission.Leadership is
      not a personal trait but is learnable skill. Leadership is a journey where one
      goes from being a member of a single team to lead health sector in working with
      other sectors. A leader moves from carrying out assigned tasks at the beginning
      of journey to providing a vision to motivate others to achieve their life goals.
      A true leader grooms leaders to establish a legacy of leadership. Ten lessons
      from my life would be: Believe in yourself; Seize the opportunities; present a
      vision of future; get out of comfort zone; expand capacity rather than define
      limits; strengthen communication and people to people skills; build a team;
      consider everyone as a potential collaborator; focus on deliverables and on
      relationships. We should start Public Health leadership course and develop core
      modules for teaching of leadership to post graduates in all medical schools.

PMID- 30232965
TI  - Sun exposure and Vitamin D in rural India: A cross-sectional study.
AB  - Background: Vitamin D deficiency/Vitamin D Insufficiency (VDI) is now recognized
      as a pandemic. Cutaneous exposure to ultraviolet-B causes photolysis of epidermal
      7-dehydrocholesterol, converting it to pre-Vitamin D3 (precholecalciferol), which
      then undergoes isomerization to form the stable hormone Vitamin D3. Objectives:
      The objectives of the study is to determine the status of Vitamin D level among
      the adults residing in a rural area of West Bengal and to find out the optimal
      cutoff of the sun exposure for Vitamin D sufficiency. Methods: This study was a
      rural community based cross-sectional study. It was done from May 2016 to April
      2017 among 197 adults residing in a rural block of West Bengal. Data were
      collected by interviewing the respondents with the help of a structured pre
      tested pre-designed schedule. After interviewing, every individual was examined
      for height and weight and blood was collected for serum Vitamin 25-(OH) D.
      Receiver Operating Characteristic (ROC) curves were utilized to find out optimum
      cut-off for sun exposure using Youden's index. Binary logistic regression was
      performed to find out the associates of high sun exposure. All analysis was done
      using R. Results: Overall VDI was found in 133 (67.5%). Among them, 102 (51.8%)
      were female. On ROC curve for veritable sun exposure for Vitamin D sufficiency,
      area under curve was 0.7841 which signifies veritable sun exposure as a good
      screening tool. Conclusion: Proper information, education, and communication
      material regarding various aspects of sun exposure and Vitamin D should be
      prepared with due consultation of field experts and disseminated to increase
      awareness among the community.

PMID- 30232967
TI  - Incidence of congenital anomalies in a rural population of Jammu - A prospective
      study.
AB  - Background: Congenital anomalies (CAs) are a major cause of stillbirths and
      neonatal mortality in India. Its magnitude and pattern reportedly vary over time
      and across geographical locations. Objectives: The objective of the study is to
      estimate the incidence of CAs in community development block RS Pura of District
      Jammu. Methods: The present study is a community-based prospective study. The
      field workers were trained with the help of "Birth Defect Surveillance" Atlas
      issued by WHO and ICBDMS (International Clearinghouse for Birth Defects
      Monitoring Systems) 2014. Pregnant women (registered or unregistered) with all
      health institutions in RS Pura Block on or after April 1, 2014, were followed
      till September 2015 for the ascertainment of CAs. All CAs detected during
      antenatal period (by ultrasonography), after delivery and abortion at any site
      were counted as events and classified by organ system according to the 10th
      version of the WHO International Classification of Diseases-10. Results: A total
      of 1670 mothers were followed till their pregnancy outcome was recorded. Among
      1600 live births recorded, 54 babies had CAs resulting in the incidence rate of
      33.7/1000 live births. The incidence rate was comparatively higher among women
      aged <20 years (71.4/1000 live births) and with Para 4 (43.5/1000 live births) as
      compared to other women. Digestive system was the most common system involved
      (35%) followed by the Central nervous system (26.6%). The U-shaped pattern in the
      incidence of CAs with regards to parity and maternal age was observed.
      Conclusion: The study demonstrated that the CAs continue to occur in Jammu at a
      similar magnitude as reported from other parts of the country.

PMID- 30232966
TI  - Exposure to indoor air pollution and its perceived impact on health of women and
      their children: A household survey in a slum of Kolkata, India.
AB  - Background: One's house is believed to be the safest and the healthiest place to
      live in. Indoor air pollution (IAP) means the presence of unwanted substances in
      the indoor air at concentration toxic to health. Objective: The objective of this
      study is to study the presence of IAP, its associated factors and impact on
      health of women residing in an urban slum of Kolkata, West Bengal, India.
      Methods: It was a cross-sectional study done from January 2017 to March 2017
      among 120 households of a slum. Data were collected using a pre-designed pre
      tested schedule from the homemaker of the households. All analyses were conducted
      with R: A Language and Environment for Statistical Computing. Results: About 60%
      households used kerosene as cooking fuel predominantly. Smoke from the
      neighbouring houses troubled 57.5% respondents. More than 60% houses were
      overcrowded and more than 70% houses were poorly ventilated. IAP-related symptoms
      such as irritation in the eye, suffocation, dry cough significantly correlated
      with the presence of IAP sources and its contributory factors. Of 120, 78 (65%)
      perceived the presence of IAP in their houses. Lower per capita income (PCI),
      ground floor, and joint family were found to have higher odds of sources of IAP.
      Younger age, lower PCI, and ground floor were found to be strongly associated
      with higher contributory factors of IAP. Conclusion: The present study found that
      the majority of the households were exposed to IAP due to kerosene, neighborhood
      smoke while overcrowding and ill-ventilation accentuated it. Effective
      intervention with intersectoral coordination is the need of the hour.

PMID- 30232968
TI  - Basis of science policies for infectious disease challenges in India.
AB  - With increase in drug resistance and related challenges in infectious diseases
      globally, it has become more important for a country like India with a high
      population to develop strategies to deal with such challenges. The literature
      review was conducted using the Google search engine to explore the contemporary
      science policies in India (since 2012) which are designed for tackling infectious
      diseases challenges in the country. This review article gives an insight into the
      strengths and limitations of the basis of some of the contemporary science
      policies in India that are drafted and implemented to combat the challenges of
      infectious diseases. The new national plans for controlling infectious disease
      challenges with bold strategies for their rapid and effective implementation hold
      promise in India.

PMID- 30232969
TI  - Problematic internet use among students in South-East Asia: Current state of
      evidence.
AB  - Problematic Internet use (PIU) among students has become a significant mental
      health concern. Our goals were to review the existing studies on problematic
      Internet from Southeast Asian Region and examine: the prevalence for PIU among
      students; explore for sociodemographic and clinical correlates; and assess the
      physical, mental, and psychosocial impact of PIU in this population. All studies
      conducted among population of the Southeast Asia, involving students (school
      students to postgraduate students) of any age which explored etiological factors
      and/or the prevalence or any other factor associated with PIU/Internet addiction
      were considered eligible for the present review. The electronic databases of
      PubMed and Google Scholar were systematically searched for the relevant published
      studies up to and including October 2016. Our search strategy yielded 549
      articles, 295 of which were eligible for screening based on their publication in
      English language in a peer-reviewed journal. Of these, a total of 38 studies met
      the inclusion criteria and were included in the review. The prevalence of severe
      PIU/Internet addiction ranged from 0 to 47.4%, whereas the prevalence of Internet
      overuse/possible Internet addiction ranged from 7.4% to 46.4% among students from
      Southeast Asia. Physical impairments in the form of insomnia (26.8%), daytime
      sleepiness (20%), and eye strain (19%) were also reported among problem users.
      There is a need to conduct further research in this area to explore the
      protective and risk factors associated with it and also longitudinally assess the
      trajectories of the outcome.

PMID- 30232970
TI  - Surgical conditions - A neglected aspect of public health: Call to action.
AB  - The burden of surgical conditions is large, though unrecognized. Surgical
      interventions are cost - effective, but thought to be otherwise. Investments
      aimed at including surgery at primary care level are affordable. Globally, a
      momentum is being created to strengthen surgery infrastructure especially for the
      poor in the low and middle income countries - who bear the burden most. In India,
      the Association of Rural Surgeons of India, and a body for implementing Lancet
      Commission of Global Surgery, India are taking lead. A blue print of activities
      needed to bring surgery on the centre stage of public health in India has been
      developed. The IPHA can play a catalytic role and use its convening power in
      getting various associations of public health professionals in India to partner
      surgeons in this effort. Integration of surgery in public health has the
      potential to improve equity, access, and universal health coverage.

PMID- 30232972
TI  - Risk of relapse in clients with alcohol dependence syndrome in a tertiary care
      hospital.
AB  - Alcoholism is one of the major health problems seen all over the world. The risk
      of relapse was estimated among 94 clients with alcohol dependence syndrome (ADS)
      who attended both in- and out-patient units of a tertiary care hospital. The
      tools used were the sociodemographic and clinical variables, Clinical Institute
      of Withdrawal Assessment Alcohol-revised (CIWA-Ar), Alcohol Use Disorder
      Identification Test (AUDIT), and Advanced Warning of Relapse (AWARE) scale. Out
      of the 94 clients, 63 (67.7%) were in the low-risk group for getting relapse, 26
      (27.7%) were in the moderate-risk group, and 5 (5.3%) were in the high-risk
      group. Family history of alcohol use was significantly associated with the AWARE
      score (P < 0.05). Nicotine use was reported by 56 (59.6%) clients. Clients with a
      positive family history of alcohol use, disturbed sleep pattern, and higher total
      score (>20) of AUDIT scale were at higher risk of relapse.

PMID- 30232971
TI  - Urban health: Needs urgent attention.
AB  - Urban population in our country has increased at an annual rate of 2.7% during
      the last decade and it is estimated that by 2031, there would be about 600
      million people living in urban India. The fast pace of urbanization has come to
      stay with increasing proportion of urban poor and vulnerable with health
      indicators much worse than their rural counterparts. The need to provide health
      care to urban poor has been emphasized in the past in various health committees'
      reports and National 5-year Development Plans, but no significant dent was made
      to improve the urban health scenario of the country. The National Urban Health
      Mission launched in May 2013 provides us a concrete mechanism to address special
      health needs of urban population with focus on urban poor. There is a strong need
      to set up primary healthcare system in urban areas and systematically deal with
      urban health challenges in terms of vector-borne diseases, rising incidence of
      noncommunicable diseases, air pollution and acute respiratory infections, road
      traffic accidents, trauma, and injuries. The initiatives to address these
      challenges do not remain confined to health sector alone but also need to be
      supported by sectors other than health such as social welfare, women and child
      development, road transport and highways, school education, drinking water, and
      sanitation. We really need to address wider and social determinants of health to
      effectively improve the urban health scenario.

PMID- 30232973
TI  - Cancer trends in India: A review of population-based cancer registries (2005
      2014).
AB  - There is a constant rise in cancer cases, but the trends and pattern vary
      according to the geographical region. The aim of this brief research was to
      present an update of all cancer incidences through age-adjusted rates and their
      changes in different regions of the country. The data for this study were
      obtained from published reports of 28 population-based cancer registries (2005
      2014) in India. Among males, currently, East/Northeast region ranked first, on
      the basis of incidence of cancer cases. Out of 28 registries, 11 registries
      encountered lung cancer as the leading site. Currently, East/Northeast regions
      were ranked first on the basis of incidence of cancer cases among females. Our
      study showed that 20 registries among the 28 had breast cancer as the leading
      one. Thus, the present overview revealed that all cancers in both males and
      females are consistent and had a high incidence in East/Northeast region of the
      country.

PMID- 30232974
TI  - Effectiveness of randomized control trial of mobile phone messages on control of
      fasting blood glucose in patients with type-2 diabetes mellitus in a Northern
      State of India.
AB  - Limited availability of randomized control trial warranted the conduct of a
      present study to demonstrate the effectiveness of mobile phone-based short
      message services (SMSs) on reduction in mean fasting blood glucose (FBG) in
      patients with type-2 diabetes mellitus. A total of 955 patients were recruited
      from primary and secondary health-care facilities and randomized to intervention
      (479) and control (476) group. Messages were delivered to patients for 12 months
      tailoring to their recent FBG values. SMS included information to maintain the
      desired FBG levels and next due date for FBG assessment. Patients were
      statistically similar for their age, socioeconomic status, smoking, and alcohol
      use. After the intervention, an average FBG declined from 163.7 to 152.8 mg/dl (P
      = 0.019) in intervention and from 150.5 to 149.2 mg/dl (P = 0.859) in control
      group. Adjusted for the baseline FBG, the intervention was found to be
      significantly effective (odds ratio: 1.7; 95 confidence interval: 1.2-2.6).

PMID- 30232975
TI  - Water, sanitation and hygiene survey - Use of hydrogen sulfide strip at field
      level as a point-of-care test: A pilot study.
AB  - Safe drinking water is a basic element of primary health care. The government of
      India in its Indian Public Health Standards recommends the hydrogen sulfide (H2S)
      strip test as a desirable component at primary health centers for screening water
      for fecal coliforms. The objective of the present study was to conduct a water,
      sanitation and hygiene (WASH) survey followed by a H2S strip test of drinking
      water in a village with ninety households. The test was positive in 88% at the
      source and the point of consumption, with 100% concordance between both the
      points of test. A subsample of water samples was subjected to testing in
      microbiology laboratory, and fecal contamination was confirmed in all of them. To
      conclude, H2S strip test can be conveniently used at field level, and its ease of
      use and visual nature of results make it a useful point-of-care test of
      environmental and public health.

PMID- 30232976
TI  - Hepatitis E infection in Odisha, India: A descriptive analysis.
AB  - Up to 25% of hepatitis E virus (HEV)-infected pregnant women in their third
      trimester die. Despite HEV being an important cause of viral hepatitis, no robust
      surveillance exists in India. We reviewed jaundice outbreaks records and hospital
      records from jaundiced individuals seeking treatment and linked those records to
      laboratory results (HEV immunoglobulin M enzyme-linked immunosorbent assay) for
      January 2012 to September 2013 in Odisha state. A total of 14 HEV confirmed
      outbreaks were identified, of which 33% of 139 jaundiced cases were HEV positive.
      There were two deaths. An additional 495 jaundiced cases were identified through
      hospital records, of which 18% were HEV positive. Among HEV-positive women (n =
      35), 34% were of childbearing age. While one may not be able to generalize our
      results, this finding suggests HE is widespread in Odisha and may represent
      hidden disease burden in this region. The policymakers should monitor HEV
      infections in similar geographical areas, especially among population of
      childbearing age women to initiate evidence-based control measures.

PMID- 30232977
TI  - "Near-Miss obstetric events" and its clinico-social correlates in a secondary
      referral unit of Burdwan District in West Bengal.
AB  - Near-miss obstetric events (NMEs) refers to the situations where women experience
      severe, life-threatening obstetric complications during pregnancy, delivery, or
      postpregnancy (up to 42 days) which they survive either by chance or because they
      receive good care at a facility. A cross-sectional study was conducted from May
      to June 2016 at the subdivisional hospital of West Bengal. The WHO near-miss
      criteria were followed for case identification. Data were collected by interview
      and record review. No maternal deaths were reported during data collection
      period; however, the frequency of NMEs was quite high (38%). Maternal near-miss
      ratio was 379.51/1000 live births, and maternal mortality index was 0%. Higher
      age group, below poverty line status, term pregnancy, and higher gravid and
      higher parity significantly favored the occurrence of NMEs, while ANC
      registration and Iron and Folic Acid consumption were significantly protective
      against it. Early identification of risk factors for NMEs and prompt initiation
      of treatment plays a critical role in the management of NMEs.

PMID- 30232978
TI  - Phthiriasis palpebrarum presenting as anterior blepharitis.
AB  - In humans, Pthirus pubis or crab louse usually infests hair of pubic region.
      Phthiriasis palpebrarum (infestation of the eyelashes and eyelids) is not as rare
      as is reported in literature, especially in low socioeconomic communities. It is
      possible that the disease is being perhaps missed due to its clinical similarity
      with anterior blepharitis. The nits and adult lice adhering to the eyelashes can
      easily be overlooked. This study presents five cases of phthiriasis palpebrarum,
      coming from the same locality and socioeconomic background, presenting with
      itching, hyperemia of lids, and excoriation of skin. Two patients were
      misdiagnosed elsewhere. All were successfully treated. The presence of P. pubis
      reflects the low level of health and hygiene of that stratum of the society.
      Higher prevalence could be related to rapid urbanization, overcrowding, and
      extreme poverty. The health-care providers and policymakers should give more
      merit to this not so uncommon disease having high morbidity.

PMID- 30232979
TI  - The cover page.

PMID- 30232980
TI  - The journey of my life and its culmination in correlative neuro-philosophy.

PMID- 30232982
TI  - Evolution of surgical techniques in the management of vertebral body tumours and
      the current status.
AB  - Primary vertebral body tumours constitute only about 5% of skeletal tumours.
      Their morbidity is high due to instability and neurological deficits related to
      the spine. The complex anatomy further highlights the expertise needed in their
      management. A multidisciplinary management has heralded tremendous improvements
      in the treatment of primary vertebral body tumours. From incomplete resection
      with a high recurrence of these tumours in the early 20th century, to the present
      day complete en-bloc excision of the tumours, guided by the well-established
      staging and classification systems, have been the significant changes brought
      about in the long course of treatment of these complex tumours. The overall
      results are better with radical excision in combination with adjuvant therapies.
      Complex and previously unimaginable surgical techniques are accomplished easily
      with a multi-disciplinary approach and with newer spinal instrumentation.
      Understanding of the evolution of surgical techniques and the prevalent
      classifications are essential in the surgical management of vertebral body
      tumours.

PMID- 30232981
TI  - Founders of Indian Neurosciences: Professor Vijay Shanker Dave-The inspiring
      initiator of neurosurgery in Uttar Pradesh.

PMID- 30232983
TI  - From subconscious to conscious to artificial intelligence: A focus on electronic
      health records.
AB  - A paradigm shift in human evolution, from our predecessors, the 'hunter
      gatherers' to the 'era of digital revolution', has made certain human skills more
      and more machine driven. This digital revolution has made possible a constant
      connectivity, wearable technologies, customized platforms, enormous data storage
      and cloud computing at high speeds, smart phones and apps, internet of things,
      artificial intelligence, telemedicine, etc. These have made real-time monitoring
      and interventions possible in healthcare. Most advanced countries have made
      electronic health records (EHR) mandatory. The Government of India has an agenda
      of Digital India and digital healthcare and might insist on EHRs. EHR is a real
      time, patient-centered digital version of a patient's paper record/chart,
      available instantly and securely to authorized users. EHR contains a patient's
      medical history, diagnosis, medications, treatment plans, immunization dates,
      allergies, radiological images, and laboratory results. It can access evidence
      based tools that help to make safer decisions about a patient's care with
      enhanced decision support, clinical alerts, reminders and medical information.
      The procedure is also more reliable for dispensing medications and introduces the
      convenience of e-prescriptions. While the advanced technology and digital devices
      are well received by the healthcare providers, universal acceptance of the EHRs
      is far from achieving its full potential. The author, in this paper, discusses
      the current scenario and issues concerned with EHRs in the digital healthcare.

PMID- 30232984
TI  - Considerations for young neurologists/neurosurgeons on how to negotiate a
      contract in a private hospital.

PMID- 30232985
TI  - Commonly available outcome measures for use in Indian boys with Duchenne muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder. It is still
      an incurable disease and many clinical trials are going on to find the cure for
      this disease. There is a need for sensitive and reliable measures for detecting
      the disease progression. This manuscript focuses on reviewing the different
      outcome measures which can be used in the Indian DMD patients.

PMID- 30232986
TI  - Zika virus: A wake up call.

PMID- 30232987
TI  - Zika virus and Guillain-Barre syndrome: Cause or association?

PMID- 30232988
TI  - Guillain-Barre syndrome caused by Zika virus: A wake-up call for India.

PMID- 30232989
TI  - Opsoclonus myoclonus ataxia syndrome.

PMID- 30232990
TI  - Opsoclonus myoclonus syndrome in children: Paraneoplastic versus parainfectious.

PMID- 30232991
TI  - Balance the fluid....

PMID- 30232992
TI  - Is buffered crystalloid safer than normal saline in neurosurgery?

PMID- 30232993
TI  - Evolution of motor therapies in stroke rehabilitation: An eternal path.

PMID- 30232994
TI  - Exercises after stroke: The essential endurance.

PMID- 30232995
TI  - Surgical taming of petroclival meningiomas: King Cobra of all skull base tumors.

PMID- 30232996
TI  - Large-to-giant petroclival meningiomas: The additional features in management.

PMID- 30232997
TI  - Posterior reversible encephalopathy syndrome in eclampsia.
AB  - Posterior reversible encephalopathy syndrome is characterized by acute headache,
      visual impairment, seizures, and altered mental status; neuroimaging may show
      cerebral edema affecting the parietal and occipital lobes of the brain. The
      objective of this article is to review the current understanding of posterior
      reversible encephalopathy syndrome in eclampsia. Literature was searched from
      PubMed, Scopus, and Google Scholar databases. The search terms included
      "eclampsia", "eclampsia and posterior reversible encephalopathy syndrome", and
      "pregnancy and posterior reversible encephalopathy syndrome". We reviewed all
      published original articles with the search term "posterior reversible
      encephalopathy syndrome". Up to 100% of eclamptic patients may have reversible
      posterior leukoencephalopathy syndrome. Two putative mechanisms - "vasogenic" and
      "vasospasm" - are considered to be responsible. Cerebral edema and petechial
      cortical hemorrhages are common autopsy findings. Clinical and neuroimaging
      manifestations are reversible in the majority of patients. Prompt correction of
      increased blood pressure and treatment of seizures are the cornerstones of
      treatment. Magnesium sulfate is the drug of choice for seizures. Some survivors
      may have permanent vision loss and other disabling sequelae. In conclusion,
      posterior reversible encephalopathy is a devastating complication of eclampsia.
      Early recognition helps in preventing some of its devastating sequelae.

PMID- 30232998
TI  - Antibodies to Zika virus, Campylobacter jejuni and gangliosides in Guillain-Barre
      syndrome: A prospective single-center study from southern India.
AB  - Background: The objective of this article was to study the presence of antibodies
      against Zika virus (ZIKV), Campylobacter jejuni, and gangliosides in patients
      with Guillain-Barre syndrome (GBS). Materials and Methods: Ninety consecutive
      patients (age more than 12 years) with GBS admitted to a tertiary care center in
      southern India were included in this study. Data on clinical manifestations,
      nerve conduction studies, and response to therapy were collected. The following
      tests were done in stored serum samples - anti-ZIKV (IgM) antibodies, anti-C.
      jejuni (IgG) antibodies, and anti-ganglioside antibodies (IgG). Those samples
      which were positive to anti-Zika antibodies were tested for conventional
      polymerase chain reaction for ZIKV and IgM antibodies against dengue, and
      Japanese encephalitis virus. Results: Of the 90 patients, 3 died and 8 had
      persistent weakness. Acute inflammatory demyelinating polyradiculoneuropathy was
      the most common type of GBS (56.7%). Anti-ganglioside antibodies were present in
      62.2% patients with GT1b being the most common. Anti-C. jejuni antibodies were
      present in 46.6%. Anti-Zika antibodies (IgM) were present in 14 patients (15.5%).
      Four of these patients also had anti-dengue antibody (IgM) positivity.
      Conclusion: This is one of the largest studies on GBS from India and the first
      one to report on the presence of Zika virus antibodies from this geographical
      area. Our study had a high prevalence of anti-C. jejuni and anti-ganglioside
      antibodies. Evidence of recent ZIKV infection, as evidenced by anti-IgM
      antibodies, was present in 14 patients, with 4 of them being tested positive for
      anti-dengue IgM antibody. Whether this represents cross-reaction with dengue or
      prior/co-infection with dengue virus could not be addressed in this study.

PMID- 30232999
TI  - Pediatric opsoclonus-myoclonus-ataxia syndrome: Experience from a tertiary care
      university hospital.
AB  - Background: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder; there
      is limited experience regarding its clinical course and therapeutic response.
      Aims and Objectives: To describe the clinical profile, investigations, and
      therapeutic outcome in pediatric OMAS. Patients and Methods: Fourteen children
      (age: 27.1 +/- 7 months; male: female = 1:2.3) suffering from OMAS seen over a
      period of 10 years (2006-2015) were included in the study. Their
      clinicodemographic profile, investigations, therapeutic outcome at follow-up, and
      relapses were reviewed. Results: Ten children reported antecedent events
      (respiratory infection: 7; gastrointestinal infection: 1; vaccination: 2). The
      most common referral diagnosis was acute cerebellitis (n = 8). Hypotonia (n = 9),
      abnormal behavior (n = 10), and neuroregression (n = 6) were also the frequent
      manifestations. Brain magnetic resonance imaging, cerebrospinal fluid, and
      urinary vanillylmandelic acid were normal in all the patients. Seven patients had
      an underlying tumor (abdomen: 4; thorax: 2; neck: 1) detected by ultrasound (n =
      2/14), computed tomography (CT) (n = 6/12), and fluorodeoxyglucose - positron
      emission tomography (n = 2/2). CT scan identified the tumor in 2 patients where
      metaiodobenzylguanidine scintigraphy was negative. All patients received steroids
      for 22.3 +/- 20 months (3 months to 5 years). Eight required prolonged
      immunomodulation (>12 months). Complete remission after follow-up of 31.3 +/- 19
      months (7 months to 5 years) was noted in 5 patients, whereas the rest had
      persisting behavioral and cognitive abnormalities. Relapses were noted in 6
      patients related to intercurrent infections (n = 5) and discontinuation of
      steroids (n = 1). The patients presented with isolated symptoms of the full-blown
      syndrome during their relapses. Conclusion: OMAS in children runs an indolent
      course requiring careful monitoring and long-term immunomodulation. An abnormal
      behavior is common and the outcome is variable.

PMID- 30233000
TI  - Comparison of normal saline and balanced crystalloid (plasmalyte) in patients
      undergoing elective craniotomy for supratentorial brain tumors: A randomized
      controlled trial.
AB  - Background: The choice of fluid is important in neurosurgical patients, who may
      be dehydrated due to the administration of diuretics in order to reduce cerebral
      edema. Normal saline, the infused fluid routinely used in neurosurgical patients,
      can cause hyperchloremic metabolic acidosis. A balanced crystalloid (BC) may help
      to maintain the metabolic status more favorably in these patients, without
      adversely affecting brain relaxation. Methods: We conducted a prospective,
      randomized controlled trial on patients undergoing elective craniotomy for
      supratentorial tumor resection under general anesthesia. 44 patients were
      randomly allocated into two groups of 22 each to receive either normal saline or
      BC (Plasmalyte) as the maintenance fluid, intra-operatively. The metabolic
      parameters and osmolality were measured at regular intervals. Brain relaxation
      score was assessed by the operating surgeon. The patients were monitored with
      serum neutrophil gelatinase-associated lipocalin (NGAL), blood urea and serum
      creatinine for assessing the degree of acute kidney injury. Results: The
      metabolic profile was better maintained with the BC. The brain relaxation score
      was comparable between the two groups. The postoperative NGAL, urea and
      creatinine values were significantly higher in the normal saline group compared
      to the BC group. Conclusion: The balanced crystalloid maintains metabolic status
      more favorably than normal saline in neurosurgical patients. Hyperchloremic
      metabolic acidosis, and the other problems which occur as a consequence of normal
      saline infusion may be circumvented by choosing a balanced crystalloid
      electrolyte solution. Neither of the crystalloids appeared to have any adverse
      effect on brain relaxation.

PMID- 30233001
TI  - Role of corrected-assisted-synchronized-periodic therapy in post-stroke
      rehabilitation.
AB  - Background: Stroke is one of the common causes of chronic disability among
      neurological disorders. The role of various physiotherapy techniques has been
      extensively described in the literature. Here, we introduce a new physiotherapy
      technique, "Corrected-Assisted-Synchronized-Periodic (CASP) therapy." In this
      study, we aimed to compare CASP therapy with conventional physiotherapies.
      Materials and Methods: This was a prospective, parallel, quasi-randomized, double
      blind controlled intervention trial. The study was carried out at a tertiary care
      teaching and research centre. Sixty-one stroke affected patients with functional
      modified Rankin Scale (mRS) ranging from 1 to 5 suffering from post-stroke
      spasticity (grade 1-4) and muscle weakness were included in the study. Patients
      were randomly allocated into two groups. The first group followed conventional
      passive stretching exercises and the second group was offered CASP therapy. They
      were prospectively followed up at 3 monthly intervals for 6 months. The main
      outcome-measures were improvement in power, reduction in spasticity, and
      improvement in overall functional outcome. Results: Mann-Whitney U-test for
      statistical significance was applied. At follow-up, CASP recipients reported
      improvement on functional scales such as Barthel index of activity of daily
      living, and modified Rankin scale (mRS), along with reduction in post-stroke
      spasticity and improvement in muscle power at 3 and 6 months of follow-up.
      Conclusion: CASP therapy has a major role in post-stroke rehabilitation
      particularly in limiting disability, reducing post-stroke spasticity, and
      providing an improvement in major functional outcomes.

PMID- 30233002
TI  - Pituitary dysfunction in survivors of Russell's viper snake bite envenomation: A
      prospective study.
AB  - Purpose: Endocrinal insufficiency caused by vasculotoxic snake envenomation is
      under-recognized and is mostly confined to a specific geographic area. We
      conducted a prospective study to determine the prevalence and pattern of
      pituitary-target gland insufficiencies caused by snake envenomation. Materials
      and Methods: The hormonal evaluation of patients who had suffered from
      vasculotoxic snake envenomation was done at baseline and at 6 months of follow
      up. Those patients with a documented hormonal insufficiency underwent magnetic
      resonance imaging (MRI) of the hypothalamo-pituitary area. The severity of
      envenomation was assessed by the acute physiology and chronic health evaluation
      II (APACHE-II) score, the sepsis-related organ failure assessment (SOFA) score,
      and the snake bite severity score (SBSS) for all patients. Results: Seventy-six
      patients were seen during the study period, of which 60 were available for a
      repeat hormonal evaluation at 6 months, with the majority of patients belonging
      to the middle age group (mean age, 37.6 +/- 14.9 years). The mean lag period at
      presentation was 32 +/- 20 h. Thirty-five patients (46.1%) had coagulopathy, 20
      patients (26.3%) had acute kidney injury (AKI), and 8 of 76 patients (10.5%)
      needed renal replacement therapy (RRT) in the form of hemodialysis. Six patients
      (out of 41 with vasculotoxic bites) developed chronic hypopituitarism, which was
      in continuation with the acute hypopituitarism that they developed. Growth
      hormone and glucocorticoid deficiencies were the most common endocrinopathies
      observed. The occurrence of hypopituitarism was observed only in patients with a
      vasculotoxic snake bite (due to Russell's viper); coagulopathy, renal
      insufficiency, or any of the scoring tools did not predict the occurrence of
      hypopituitarism. Conclusion: Acute asymptomatic and chronic symptomatic or
      asymptomatic hypopituitarism are important sequelae of viper bite in a small
      proportion of patients and can occur in the presence of normal pituitary imaging.
      Routine prospective pituitary hormone screening should be done in all patients
      within the first 6 months of envenomation by the vasculotoxic snakebite as
      chronic pituitary dysfunction can often occur in these patients.

PMID- 30233003
TI  - Degree centrality and voxel-mirrored homotopic connectivity in children with
      nocturnal enuresis: A functional MRI study.
AB  - Aim: To determine the characteristics of brain development in children with
      nocturnal enuresis, we investigated the intensity of functional connectivity both
      among the nodes in the brain network and between the two hemispheres of the
      brain. Materials and Methods: Twenty-three children with nocturnal enuresis (NE)
      and an equal number of normal children were examined using resting-state
      functional magnetic resonance imaging (fMRI) scans. Data analysis was done via
      the degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC)
      approaches. Moreover, we compared the children's psychological status by
      utilizing the self-concept scale. Results: In four areas of the brain, the the DC
      values of the NE group were obviously lower than that of the normal controls.
      These four areas were the posterior cerebellar lobe, anterior cingulate cortex
      (ACC), medial frontal gyrus, and superior left temporal gyrus (P < 0.05, after
      correction). We also found two brain areas where the VMHC values of the NE group
      were obviously lower than that of the normal controls. The two groups were the
      cerebellar lobe and the anterior cingulate cortex (ACC) [P < 0.05, after
      correction]. A psychological comparison between the children with NE and that in
      the normal group on the self-concept scale was also performed. The scores of the
      children with NE were lower than normal controls regarding behavior, appearance
      and property, anxiety, gregariousness, happiness, and satisfaction (P < 0.05).
      Conclusions: These findings provide evidence of the deficit of urination control
      in children with NE. Furthermore, through the methods of DC and VMHC, which are
      based on functional connectivity, it was also possible to explain why children
      with NE often have the concomitant symptoms of attention, control, and memory
      problems. The analysis of the self-concept scale suggests that children with NE
      lack self-confidence.

PMID- 30233004
TI  - Brain networking in primary monosymptomatic nocturnal enuresis: News from Brain
      Bladder-Control matrix.

PMID- 30233005
TI  - Assessing functional connectivity of brain network in children with nocturnal
      enuresis using resting state functional magnetic resonance imaging.

PMID- 30233006
TI  - Identification of microdeletion and microduplication syndromes by chromosomal
      microarray in patients with intellectual disability with dysmorphism.
AB  - Background: A retrospective analysis using chromosomal microarray in syndromic
      patients with intellectual disability from genetic clinics of a tertiary
      healthcare center in India was conducted. Aim: To identify the spectrum of
      chromosomal abnormalities detected on microarray analysis. Settings and Design:
      Cases were identified among those with intellectual disability with dysmorphism
      attending genetic clinics of a tertiary care center. Patients and Methods: All
      patients attending genetic clinics over a 3-year period were analyzed. Clinical
      profile and baseline investigations were noted on a predesigned proforma. Among
      the 65 studied cases, there were 12 cases suggested to be having Prader-Willi
      syndrome (PWS), 27 cases with DiGeorge/velocardiofacial syndrome (DGS), and 1
      case with Williams-Beuren syndrome (WBS). These were detected by fluorescent in
      situ hybridization (FISH) analysis with specific probes and were excluded from
      the final analysis. Chromosomal microarray analysis (CMA; single-nucleotide
      polymorphism-based array-comparative genomic hybridization) was performed as per
      the clinical indication in selected patients with dysmorphism, microcephaly,
      mental retardation, and/or multiple malformations. These patients had a negative
      result on FISH analysis. Results: In suspected patients with PWS, FISH and
      methylation testing confirmed six cases to be really PWS. FISH also detected five
      cases of DGS and one case of WBS. These were excluded from the final analysis.
      Among the 18 cases tested by CMA, in 13 patients, abnormalities with potential
      clinical significance were identified. Genetic counseling was done in all these
      cases. Prenatal diagnosis was done in one family. Conclusion: In cases with
      dysmorphism with or without mental retardation or cardiac defect, advanced
      studies such as CMA can lead to a definitive diagnosis. Genetic counseling is
      mandatory in all these cases and a prenatal diagnosis is also feasible in
      selected families.

PMID- 30233007
TI  - Accuracy and reliability of Babinski sign versus finger and foot tapping in the
      diagnosis of corticospinal tract lesions.
AB  - Introduction: The Babinski sign is one of the most important clinical signs for
      detecting corticospinal tract (CST) lesions. However, due to variations in
      testing and interpretation, it has been associated with low interobserver
      agreement rates. In this study, the diagnostic value of finger and foot tapping
      in detecting CST lesions was compared to that of the Babinski sign. Materials and
      Methods: Three groups of participants were recruited: Group 1 - individuals
      having CST lesions diagnosed on the basis of clinical examination as well as
      neuroimaging; group 2 - individuals having a non-CST neurological illness; group
      3 - normal individuals who were relatives of the patients recruited. The
      sensitivity and specificity of finger tapping, foot tapping, and Babinski sign
      were calculated. Results: 375 patients, 125 in each group, were included. The
      overall sensitivity for Babinski sign was 49.6% and specificity was 85.8%. The
      overall sensitivity for finger and foot tapping was 79.5% and specificity was
      88.4%. The interobserver agreement between the medical students and the
      neurologist was greater for finger and foot tapping (Kappa = 0.83) when compared
      to Babinski sign (Kappa = 0.45). Conclusion: Finger and foot tapping is a valid
      and reliable test in the clinical diagnosis of corticospinal lesions. The
      reliability and validity of Babinski sign is variable and thus its ability to
      diagnose the manifestations of corticospinal lesions is less when compared to the
      finger and foot tapping test.

PMID- 30233008
TI  - Accuracy and reliability of Babinski sign versus finger and foot tapping in the
      diagnosis of corticospinal tract lesions.

PMID- 30233009
TI  - Evaluation of NT-ProBNP as a marker of the volume status of neurosurgical
      patients developing hyponatremia and natriuresis: A pilot study.
AB  - Objective: Post-operative hyponatremia (serum sodium <130 mEq/L) contributes to
      morbidity and prolongs the hospital stay of patients undergoing neurosurgical
      procedures. Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) and
      cerebral salt wasting (CSW) commonly occur in the post-operative setting. While
      patients with SIADH are either euvolemic or hypervolemic, patients with CSW are
      always hypovolemic. The treatment of these two conditions is radically different.
      Patients with SIADH need fluid restriction, while patients with CSW need fluid
      replacement. As current diagnostic methods do not clearly distinguish between
      SIADH and CSW, we looked at N-terminal prohormone of brain natriuretic peptide
      (NT-proBNP) and uric acid as biochemical markers for estimating the volume status
      of patients developing hyponatremia in the postoperative period. Materials and
      Methods: In this study, we used a cohort design and carried it out in two phases
      over a period of 30 months (August 2011-February 2014). Thirty-one patients with
      hyponatremia were recruited into the study. In Phase1, 10 patients were diagnosed
      to have either SIADH or CSW based on their central venous pressure (CVP). In all
      of them, blood for NT-proBNP was collected prior to starting treatment. At a
      later stage, the NT-proBNP results were compared with central venous pressure
      (CVP) and the clinical diagnosis. Patients diagnosed to have SIADH (CVP >5cm) had
      NT-proBNP levels <125pg/ml and those with a diagnosis of CSW (CVP <5cm) had NT
      proBNP levels >125pg/ml. In Phase2, 21 patients were categorized and treated
      according to their NT-proBNP levels. Those with NT-proBNP levels <125 pg/ml were
      treated as SIADH, and those with NT-proBNP levels >125 pg/ml were treated as CSW.
      Results: In Phase 1, NT-proBNP could detect hypovolemia in patients with CSW with
      100% sensitivity and 66.7% specificity (P < 0.07). In Phase 2, NT-proBNP could
      detect hypovolemia in patients with CSW with 90% sensitivity and 100% specificity
      (P < 0.001). Combining the results of Phase 1 and Phase 2, NT-proBNP could
      diagnose CSW with 87.50% sensitivity and 93.33% specificity (P < 0.001). The
      positive predictive value was 93.33% and the negative predictive value was
      87.50%. Conclusion: NT Pro-BNP is a quick and convenient assay to differentiate
      SIADH and CSW. We need a larger sample size to correctly characterize the cut off
      value. Uric acid cannot be used to distinguish between SIADH and CSW.

PMID- 30233010
TI  - Role of NT-ProBNP to differentiate syndrome of inappropriate antidiuretic hormone
      secretion and cerebral salt wasting syndrome: The conundrum.

PMID- 30233011
TI  - BNP: Is it an ideal marker to assess volume status in patients with hyponatremia
      and natriuresis?

PMID- 30233012
TI  - Ossification of posterior longitudinal ligament and fluorosis.
AB  - Objective: Ossification of posterior longitudinal ligament (OPLL) is a
      progressive disease that causes spinal canal compromise and serious neurological
      sequelae in advanced cases. The incidence of OPLL in the Asiatic population is 2%
      3%, but the incidence is more in the background of fluorosis. Our aim was to
      study the association of OPLL with fluorosis by comparing urine fluoride levels
      and to study the types of OPLL. Materials and Methods: Thirty consecutive
      patients with OPLL, observed on cervical skiagram, and confirmed by the computed
      tomography (CT) of the cervical spine, underwent a 24-h urine fluoride level
      assessment by the ion-selective electrode method. Due consent of all the patients
      was obtained and the data was collected. Thirty patients with a normal cervical
      radiograph were taken as a control group and their 24-h urine fluoride levels
      were compared with the test group. The 24-h urine fluoride level above 1.6 mg/L
      was taken as the diagnostic parameter of fluorosis. Imaging analysis of the study
      group focused on the subtype of OPLL, the mass occupying ratio, the sagittal
      cervical angle, the signs of dural penetration, and the spinal levels involved.
      Urinary fluoride levels were correlated with the presence of OPLL and different
      types of OPLL. Results: Of the 30 patients with OPLL, 25 were males and 5 were
      females. The most common presentation was myelopathy. Continuous type of OPLL was
      seen in 11 (36.6%), segmental in 8 (26.6%), focal in 5 (16.6%), and mixed variant
      in 6 (20%) patients. 24-h urinary fluoride levels ranged from 0.26 mg/L to 12.2
      mg/L. 18 (60%) of the patients in the study group were found to have urinary
      fluoride levels above 1.6 mg/L and only 1 patient (4%) of the control group had
      the urine fluoride level >1.6 mg/L. This difference was statistically
      significant. Patients with continuous and mixed types of OPLL had a higher mean
      urine fluoride level than those with a segmental and focal type of OPLL. The
      continuous variant of OPLL had a statistically significant occupancy ratio when
      compared to the other three variants, and the high mass occupancy ratio of the
      OPLL was directly associated with the presence of dural penetration. Conclusion:
      Fluorosis is associated with a higher incidence of OPLL. Higher urinary fluoride
      levels correlate with the severe forms of OPLL.

PMID- 30233013
TI  - Cervical ossified posterior longitudinal ligament: Etiology and surgical
      perspectives.

PMID- 30233014
TI  - Ossified posterior longitudinal ligament with fluorosis: Implications for the
      Neurosurgeon.

PMID- 30233015
TI  - Change in average peak cerebrospinal fluid velocity at the cerebral aqueduct,
      before and after lumbar CSF tapping by the use of phase contrast MRI, and its
      effect on gait improvement in patients with normal pressure hydrocephalus.
AB  - Objectives: To compare the change in peak cerebrospinal (CSF) flow velocity at
      the cerebral aqueduct in patients with normal pressure hydrocephalus (NPH) before
      and after CSF tapping with clinical outcome of the patients, i.e., gait
      improvement. Materials and Methods: Forty patients with NPH were evaluated before
      and after CSF tapping on 3 consecutive days at our institution. Gait improvement
      was compared with the average peak velocity at the cerebral aqueduct. The average
      peak velocity was also compared before and after lumbar CSF tapping using phase
      contrast magnetic resonance imaging (PC-MRI). The different flow parameters were
      compared using paired t-test. Results: The average peak velocity before and after
      lumbar CSF tapping was 5.8196 +/- 1.420 cm/s and 4.1411 +/- 1.0638 cm/s,
      respectively. The peak positive, negative, and average velocity decreased in the
      post-tap group. In our study, 70% of the patients showed gait improvement, and a
      comparison of the gait improvement with the change in average peak velocity was
      statistically significant (P = 0.001). Comparison of the change in peak positive
      and negative velocity with gait improvement was also statistically significant,
      with a P value of 0.004 and <0.001, respectively. Rest of the CSF flow parameters
      were statistically insignificant. Conclusion: PC-MRI is a sensitive method to
      support the diagnosis of NPH. Different flow parameters were comparable before
      and after CSF tapping. The parameters which might be useful for assessing
      clinical improvement include a change in the peak average, as well as positive,
      and negative velocity.

PMID- 30233016
TI  - Is spindle cell oncocytoma a true entity or a variant of pituicytoma? A case
      report with review of literature.
AB  - Spindle cell oncocytoma (SCO) is a newly described rare entity simulating
      clinicoradiological features of a nonfunctional pituitary adenoma and is
      corresponding to the category of World Health Organization grade I tumor.
      However, because of the reported incidence of recurrence and invasive
      presentation in some cases, its categorization as a low grade tumor is
      questionable. Earlier, it was thought to arise from the folliculostellate cells
      of adenohypophysis. Recently, few reports have described expression of thyroid
      transcription factor-1 [TTF-1], which is a specific marker for pituicytes of
      neurohypophysis, suggesting this tumor to be a variant of pituicytoma. We
      describe a case of SCO in a 28-year-old young female patient with TTF-1
      immunopositivity, and ultra-structurally showing abundant mitochondria along with
      few neurosecretory granules.

PMID- 30233017
TI  - Meningeal solitary fibrous tumor/hemangiopericytoma: Emphasizing on STAT 6
      immunohistochemistry with a review of literature.
AB  - Background: The 2016 central nervous system (CNS) World Health Organisation (WHO)
      Update has merged the entities of meningeal solitary fibrous tumor (SFT) and
      hemangiopericytoma (HPC) into a single entity based on the presence of the nerve
      growth factor 1A (NGFI-A) binding protein 2 (NAB2)- signal transducer and
      activator of transcription 6 (STAT6) gene fusion in these tumors.
      Immunohistochemical (IHC) staining with STAT6 results in a strong nuclear
      positivity confirming the diagnosis. Meningeal SFT/HPCs are currently
      histologically graded according to a three-tiered system. Grade I (SFT phenotype)
      is benign, whereas grades II and III (HPC phenotype) are malignant and require
      radiotherapy in addition to gross total resection. Objectives: The objectives
      were to review the cases diagnosed as meningeal SFT or HPC between 2010 and 2017
      and classify them into SFT (grade I) or HPC (grades II and III) phenotypes; to
      confirm the diagnosis by performing STAT6 immunohistochemistry; and to observe
      and record the histological features in detail and correlate the tumor grades
      with their behavior. The published literature on the subject was also reviewed.
      Materials and Methods: A total of 21 cases diagnosed between 2010 and 2017 as
      meningeal SFT or HPC were included in the study. All cases were reviewed by the
      authors and were categorized and graded according to histologic phenotype and
      mitotic count. STAT6 immunohistochemistry was performed in all the cases. The
      epidemiological data and histologic findings in each case were recorded in
      detail. The follow-up of patients was obtained. Results: Fifteen patients were
      males and six were females. The mean age was 43.5 years. The mean tumor size was
      6.8 cm. The tumor specimens in 20 out of 21 cases corresponded to the HPC
      phenotype, of which 6 were in grade II while 14 were in grade III. Thus, over 95%
      cases had malignant lesions. The tumor in all the 21 cases recruited for the
      study showed immunohistochemical positivity for SAT6, while CD34 was positive in
      all the 18 tumor in which it was performed. The follow-up was available in 14 of
      the patients. Recurrence occurred in six patients who had either a grade II or a
      grade III tumor and three patients died (including one patient with a grade III
      tumor. This patient died a month after initial resection although there was no
      evidence of recurrence). Radiotherapy was given to only 4 out of 14 patients in
      whom follow-up was available. Conclusion: These rare tumors need to be accurately
      diagnosed and optimally treated (gross total resection and radiotherapy) to
      improve the prognosis.

PMID- 30233018
TI  - Cost analysis study of neuropsychiatric drugs: Role of National List of Essential
      Medicines, India.
AB  - Context: This study investigated the cost variation among neuropsychiatric drugs
      prevalent in the Indian market with reference to the National List of Essential
      Medicines (NLEM, 2015). Aims: To promote the rational use of medicines through
      cost variation analysis among drugs for neuropsychiatric disorders enlisted in
      NLEM and those not included in NLEM (NNLEM). Study Design: This study included
      drugs used for epilepsy, migraine, psychosis, depression, generalized anxiety
      disorder (GAD), bipolar disorder, and obsessive-compulsive disorder (OCD).
      Materials and Methods: The unit drug cost for the selected strengths of different
      manufacturers mentioned in the Current Index of Medical Specialities 2016 was
      used for calculating cost/defined daily dose (DDD). Statistical Analysis:
      Comparison was done among individual drugs and groups (NLEM and NNLEM) by
      cost/DDD in terms of interquartile range, percentage cost variation, and cost
      ratio. Results: The cost variation is wide for neuropsychiatric drugs (maximum,
      1724.3% for risperidone in NLEM, and 1780% for olanzapine in NNLEM). The drug-to
      cost ratio is the highest (168.8 times) for bipolar disorder and the lowest (9.7
      times) for GAD. The NLEM drugs were found to be more economical than the NNLEM
      drugs among antiepileptic drugs, antidepressants, and drugs for bipolar disorder;
      however, the reverse was noted for antimigraine drugs and drugs for GAD.
      Antipsychotic medications and drugs for OCD in the NLEM group have a wider range
      than in the NNLEM group. Conclusions: The NLEM group has economical drugs in some
      disease categories; there is a need to consider the cost effectiveness of all
      drug categories while revising the NLEM next time and attention should focus on
      drug price regulation policies to accomplish the goal of rational use of
      medicines.

PMID- 30233019
TI  - Surgical excision of large-to-giant petroclival meningiomas focusing on the
      middle fossa approaches: The lessons learnt.
AB  - Introduction: Petroclival meningiomas are based on or arising from the petro
      clival junction in upper two-thirds of clivus, medial to the fifth cranial nerve.
      This study focuses on the surgical experience in resecting large-giant tumors
      >3.5 in size predominantly utilizing middle fossa approaches. Material and
      Methods: 33 patients with a large or a giant petroclival meningioma (size >3.5
      cm) were included. Clinical features, preoperative radiological details,
      operative findings, and postoperative clinical course at the follow-up visit were
      reviewed. Group A tumors (n = 17,51.5%) were sized 3.5cm-5cm, and Group B (n =
      16,48.48%) tumors were of size >5 cm. Extent of resection was described as 'gross
      total' (no residual tumor), 'near total' (<10% residual tumor) and 'subtotal
      resection' (>10% residual tumor). Glasgow outcome scale (GOS) quantitatively
      scored postoperative neurological outcome (mean follow up: 35.77months; range 1
      106 months). Results: 25 (75.8%) patients had tumour extension into both
      supratentorial and infratentorial compartments. Extension into Meckel's cave (n =
      25,75.8%), cavernous sinus (n = 17,48.4%], sphenoid sinus (n = 12,38.7%] and
      suprasellar area [12,38.7%] was often seen. In 31 (93.9%) patients, the tumor
      crossed the midline in the premedullary, prepontine, and interpeduncular
      cisterns. In 20 (60.6%) patients, the tumour extended below and posterior to the
      internal auditory meatus (IAM), while in 13 (39.4%) patients, the tumor was
      located above and anterior to the IAM. Kawase's approach was the most commonly
      used approach in 16 (48.48%) patients and resulted in maximum tumor resection.
      Other approaches included half-and-half (trans-Sylvian with subtemporal) [n = 6,
      18.18%]; frontotemporal craniotomy with orbitozygomatic osteotomy [n = 1, 3%] and
      retromastoid suboccipital craniectomy (RMSO) [n = 7, 21.21%]. In 2 (6.06%)
      patients, staged anterior petrosectomy with RMSO; and, in 1, staged presigmoid
      with half-and-half approach was used. Gross total excision was achieved in 12
      (36.36%), near-total excision in 15 (45.45%) and subtotal excision in 6 (18.18%)
      patients. 20 (60.6%) patients had a good functional outcome; 6 patients succumbed
      due to meningitis, pneumonitis, perforator injury or a large tumor recurrence.
      Conclusions: Half-and-half approach was used in tumors with middle and posterior
      cranial fossae components often extending to the suprasellar region. Kawase's
      anterior petrosectomy was utilized in resecting tumors with predominant posterior
      fossa component (along with a small middle fossa component) that was crossing the
      midline anterior to the brain stem, and mainly situated superomedial to the IAM.
      Tumors confined to the posterior fossa, that extended laterally and below the IAM
      were resected utilizing the RMSO approach. Occasionally, a combination of these
      approaches was used. Middle fossa approaches help in significantly avoiding
      morbidity by an early devascularisation and decompression of the tumor. In tumors
      lacking a plane of cleavage, a thin rim of capsule of tumor may be left to avoid
      brain stem signs.

PMID- 30233020
TI  - Neurosurgery in SMS Medical College -From bare necessity to excellence.

PMID- 30233021
TI  - A summary of some of the recently published, seminal papers in neuroscience.

PMID- 30233022
TI  - Temporary noncicatricial focal alopecia following Gamma knife radiosurgery: Case
      series and review of literature.
AB  - Objective: The aim of this study is to report the pattern, timing, responsible
      radiation parameters, and dosimetric results on the outcome of alopecia following
      gamma knife radiosurgery (GKRS) for various intracranial pathologies. A
      literature review of radiation-induced alopecia and observation of this
      complication with GKRS are also included. Materials and Methods: The authors
      report 6 cases of GKRS-induced focal temporary alopecia without dermal fibrosis
      or clinical scarring and with no long-term squeal. Results: In all the cases, the
      scalp received >=3 Gy radiation exposure. Post GKRS alopecia is a temporary,
      noncicatricial, focal, reversible phenomenon observed within 2 weeks of the
      treatment. This acute complication is dose-dependent and reflects damage to the
      hair follicle. It is only seen with treated volumes in the superficial location.
      Hair regrowth occurs within two months with no long-term complications and change
      in hair quality being noted. Conclusion: Compared to whole brain radiotherapy,
      chances of alopecia are significantly less after GKRS. Despite a sharp dose
      fallout, a single fraction high-dose radiosurgery with GKRS may expose the skin
      appendages to more than 3 Gy radiation exposures, which may injure the hair
      follicles irrespective of the growth phase (anagen, telogen, or catagen) they are
      in. A careful planning that includes sparing of the dermal appendages and hair
      roots up to 4-6 mm depth in the skin may prevent this complication. Patients with
      superficial lesions should be well informed about the reversible nature of this
      possible complication, with near-normal hair growth being established within 2
      months of treatment.

PMID- 30233023
TI  - Overlap of Bickerstaff brainstem encephalitis/Guillain-Barre syndrome simulating
      brain death.

PMID- 30233024
TI  - Idiopathic retroperitoneal fibrosis presenting as spastic paraparesis.

PMID- 30233025
TI  - Unusual case of subacute cerebellar ataxia.

PMID- 30233027
TI  - A case of narcolepsy with HLA-typing from North India.

PMID- 30233026
TI  - Facial palsy: An unusual complication of vivax malaria.

PMID- 30233028
TI  - Idiopathic hypoparathyroidism with clinical and electrophysiological myotonia- An
      unusual occurrence.

PMID- 30233029
TI  - Cockayne syndrome in siblings.

PMID- 30233030
TI  - An unusual manifestation of Pisa syndrome in progressive supranuclear palsy.

PMID- 30233031
TI  - Unilateral arm flapping gait as a manifestation of synkinesis following recurrent
      strokes.

PMID- 30233032
TI  - A rare case of Japanese encephalitis-induced anti-N-methyl-d-aspartate receptor
      encephalitis.

PMID- 30233033
TI  - Peripartum seizures in Albright's osteodystrophy: Is it hypocalcemia or embolic
      stroke?

PMID- 30233034
TI  - Single-stage vertebrectomy for hydatid disease involving L3 vertebra: Five year
      follow-up.

PMID- 30233035
TI  - Balloon-assisted coil embolization of intracranial aneurysm and zero bispectral
      index.

PMID- 30233036
TI  - Gelastic seizures due to inferior frontal gyrus cavernoma.

PMID- 30233037
TI  - A rare case of spontaneous thrombosis of vein of Galen malformation in a young
      adult diagnosed on magnetic resonance imaging and digital subtraction
      angiography.

PMID- 30233038
TI  - Skull-based giant cell tumor with atypical location highlighting the importance
      of intraoperative cytological examination: Report of four cases.

PMID- 30233039
TI  - A rare case of Chiari malformation secondary to Paget's disease of skull.

PMID- 30233040
TI  - Are neurocytomas always benign?

PMID- 30233041
TI  - Hyponatremia in tuberculosis: Focus on brain instead of adrenals.

PMID- 30233042
TI  - Medulloblastoma with extensive nodularity: A rare variant with a favorable
      outcome.

PMID- 30233044
TI  - Bilateral exostosis of the external auditory canal: Surfer's ear.

PMID- 30233045
TI  - Mesenteric plexiform neurofibroma.

PMID- 30233043
TI  - Distal Sylvian fissure lipoma masquerading as a vascular malformation with bleed.

PMID- 30233046
TI  - Posttraumatic pneumorrhachis.

PMID- 30233047
TI  - Addition of pyridoxine to prednisolone in the treatment of infantile spasms: The
      knowledge gaps.

PMID- 30233048
TI  - Dengue and Japanese encephalitis E: Concurrent infection, cross reactivity, and
      false positivity.

PMID- 30233049
TI  - Pituitary aspergillosis: A report and review of the literature.

PMID- 30233050
TI  - Does 'one size fit all' in academic neurosurgery?

PMID- 30233051
TI  - The 'Uberisation' of neurosurgery and its fallacies.

PMID- 30233052
TI  - General Professor Khalaf Al Moutaery (1948-2018).

PMID- 30233054
TI  - Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis:
      perspectives and approaches.
AB  - Multiple sclerosis (MS) is characterized by chronic inflammation in conjunction
      with neurodegeneration within the central nervous system. Most individuals with
      MS begin with a relapsing remitting course that later transitions to secondary
      progressive MS. Currently available disease-modifying therapies (DMTs) for
      relapsing MS have been demonstrated to reduce disease activity, however most
      patients require a change in therapy over the course of their disease. Treatment
      goals include the prevention of relapses and disability accumulation and to
      achieve this objective requires careful planning. Sequencing of DMTs for
      individual patients should be designed in such a way to maximize disease control
      and minimize risk based on the mechanism of action, pharmacokinetic and
      pharmacodynamic properties of each therapy. This includes the DMT patients are
      being switched from to those they are being switched to. The reversibility of
      immune system effects should be a key consideration for DMT sequence selection.
      This feature varies across DMTs and should factor more prominently in decision
      making as newer treatments become available for the prevention of disability
      accumulation in patients with progressive MS. In this short review, we discuss
      the landscape of existing therapies with an eye to the future when planning for
      optimal DMT sequencing. While no cure exists for MS, efforts are being directed
      toward research in neuroregeneration with the hope for positive outcomes.

PMID- 30233053
TI  - The unfolded protein response signaling and retinal Muller cell metabolism.
AB  - The retina is one of the most energy demanding tissues in the body. Like most
      neurons in the central nervous system, retinal neurons consume high amounts of
      adenosine-5'-triphosphate (ATP) to generate visual signal and transmit the
      information to the brain. Disruptions in retinal metabolism can cause neuronal
      dysfunction and degeneration resulting in severe visual impairment and even
      blindness. The homeostasis of retinal metabolism is tightly controlled by
      multiple signaling pathways, such as the unfolded protein response (UPR), and the
      close interactions between retinal neurons and other retinal cell types including
      vascular cells and Muller glia. The UPR is a highly conserved adaptive cellular
      response and can be triggered by many physiological stressors and
      pathophysiological conditions. Activation of the UPR leads to changes in
      glycolytic rate, ATP production, de novo serine synthesis, and the hexosamine
      biosynthetic pathway, which are considered critical components of Muller glia
      metabolism and provide metabolic support to surrounding neurons. When these
      pathways are disrupted, neurodegeneration occurs rapidly. In this review, we
      summarize recent advance in studies of the UPR in Muller glia and highlight the
      potential role of the UPR in retinal degeneration through regulation of Muller
      glia metabolism.

PMID- 30233055
TI  - Targeting prion-like protein spreading in neurodegenerative diseases.
AB  - The infectious template-mediated protein conversion is a unique mechanism for the
      onset of rare and fatal neurodegenerative disorders known as transmissible
      spongiform encephalopathies, or prion diseases, which affect humans and other
      animal species. However, emerging studies are now demonstrating prion-like
      mechanisms of self-propagation of protein misfolding in a number of common, non
      infectious neurodegenerative diseases such as Alzheimer's disease and Parkinson's
      disease. It has been proposed that distinct and unrelated proteins (beta-amyloid,
      tau, alpha-synuclein, TAR DNA-binding protein 43 and huntingtin, etc.) associated
      with common neurodegenerative disorders can seed conversion and spread via cell
      to-cell transfer, sustaining the transmission of neurotoxic agents along a
      stereotypic route, sharing features at the heart of the intrinsic nature of
      prions. Here we review the most recent development on both the molecular
      mechanisms underlying the pathogenesis of prion-like neurodegenerative diseases
      as well as innovative methods and strategies for potential therapeutic
      applications.

PMID- 30233056
TI  - Cadmium-induced neurotoxicity: still much ado.
AB  - Cadmium (Cd) is a highly toxic heavy metal that accumulates in living system and
      as such is currently one of the most important occupational and environmental
      pollutants. Cd reaches into the environment by anthropogenic mobilization and it
      is absorbed from tobacco consumption or ingestion of contaminated substances. Its
      extremely long biological half-life (approximately 20-30 years in humans) and low
      rate of excretion from the body cause cadmium storage predominantly in soft
      tissues (primarily, liver and kidneys) with a diversity of toxic effects such as
      nephrotoxicity, hepatotoxicity, endocrine and reproductive toxicities. Moreover,
      a Cd-dependent neurotoxicity has been also related to neurodegenerative diseases
      such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and
      multiple sclerosis. At the cellular level, Cd affects cell proliferation,
      differentiation, apoptosis and other cellular activities. Among all these
      mechanisms, the Cd-dependent interference in DNA repair mechanisms as well as the
      generation of reactive oxygen species, seem to be the most important causes of
      its cellular toxicity. Nevertheless, there is still much to find out about its
      mechanisms of action and ways to reduce health risks. This article gives a brief
      review of the relevant mechanisms that it would be worth investigating in order
      to deep inside cadmium toxicity.

PMID- 30233057
TI  - Analysis of the trafficking system in blood-brain barrier models by high content
      screening microscopy.

PMID- 30233058
TI  - Retinal remodeling following photoreceptor degeneration causes retinal ganglion
      cell death.

PMID- 30233059
TI  - Potential therapeutic interventions based on the role of the endoplasmic
      reticulum stress response in progressive neurodegenerative diseases.

PMID- 30233060
TI  - Tissue inhibitors of metalloproteases strike a nerve.

PMID- 30233061
TI  - Inhibition of neurite outgrowth using commercial myelin associated glycoprotein
      Fc in neuro-2a cells.
AB  - Myelin-associated glycoprotein (MAG) inhibits the growth of neurites from nerve
      cells. Extraction and purification of MAG require complex operations; therefore,
      we attempted to determine whether commercially available MAG-Fc can replace
      endogenous MAG for research purposes. Immunofluorescence using specific
      antibodies against MAG, Nogo receptor (NgR) and paired immunoglobulin-like
      receptor B (PirB) was used to determine whether MAG-Fc can be endocytosed by
      neuro-2a cells. In addition, neurite outgrowth of neuro-2a cells treated with
      different doses of MAG-Fc was evaluated. Enzyme linked immunosorbent assays were
      used to measure RhoA activity. Western blot assays were conducted to assess Rho
      associated protein kinase (ROCK) phosphorylation. Neuro-2a cells expressed NgR
      and PirB, and MAG-Fc could be endocytosed by binding to NgR and PirB. This
      activated intracellular signaling pathways to increase RhoA activity and ROCK
      phosphorylation, ultimately inhibiting neurite outgrowth. These findings not only
      verify that MAG-Fc can inhibit the growth of neural neurites by activating RhoA
      signaling pathways, similarly to endogenous MAG, but also clearly demonstrate
      that commercial MAG-Fc is suitable for experimental studies of neurite outgrowth.

PMID- 30233062
TI  - Effect of acoustic stimuli in patients with disorders of consciousness: a
      quantitative electroencephalography study.
AB  - Auditory stimuli are proposed as beneficial neurorehabilitation methods in
      patients with disorders of consciousness. However, precise and accurate
      quantitative indices to estimate their potential effect remain scarce. Fourteen
      patients were recruited from the Neuro-Rehabilitation Unit of Hangzhou Hospital
      of Zhejiang Armed Police Corps of China. Altogether, there were seven cases of
      unresponsive wakefulness syndrome (five males and two females, aged 45.7 +/- 16.8
      years) and seven cases of minimally conscious state (six males and one female,
      aged 42.3 +/- 20.8 years). Simultaneously, fourteen healthy controls (10 males
      and 4 females, aged 51.7 +/- 9.7 years) also participated in this case-control
      experiment. Brain response to music, subjects' own name, and noise was monitored
      by quantitative electroencephalography (QEEG) in the resting state and with
      acoustic stimulation. Predictive QEEG values in various brain regions were
      investigated. Our results show that cerebral activation was high in subjects
      stimulated by their own name, especially in the temporal lobe in patients with
      disorders of consciousness, and the frontal lobe in the control group. Further,
      during resting and stimulation, QEEG index (delta + theta/alpha + beta ratio)
      negatively correlated with the Coma Recovery Scale-Revised score in traumatic
      disorders of consciousness patients. Hence, we speculate that a subject's own
      name might be an effective awakening therapy for patients with disorders of
      consciousness. Moreover, QEEG index in specific stimulation states may be used as
      a prognostic indicator for disorders of consciousness patients (sensitivity, 75%;
      specificity, 50%). This clinical study has been registered at ClinicalTrials.gov
      (identifier: NCT03385291).

PMID- 30233063
TI  - Symptom experience and symptom burden of patients following first-ever stroke
      within 1 year: a cross-sectional study.
AB  - Symptoms that are multidimensional and concurrent should be assessed from
      different dimensions and managed together. Few studies have evaluated concurrent
      and multidimensional symptoms in patients with stroke. Most studies of stroke
      focused on dysfunctions and complications. We hypothesize that patients with
      stroke have a heavy symptom burden within 1 year. This study aimed to describe
      multidimensional and concurrent symptoms within 1 year after stroke. This study
      recruited 230 patients with stroke from the Rehabilitation Department of Xuhui
      District Center Hospital of Shanghai and the Shanghai Sunshine Rehabilitation
      Center in China from March to September 2017. The patients' multidimensional
      symptom experience and symptom burden were analyzed using a self-made structured
      questionnaire and the influential factors for symptom burden were identified. The
      mean number of symptoms in patients with stroke was 11.7 +/- 3.5. More than two
      thirds of the participants suffered from at least 10 co-occurring symptoms.
      Unilateral limb weakness had the highest prevalence and frequency. Participation
      restriction had the highest symptom dimensions of severity and distress. Lack of
      self-care ability (severity), memory deterioration (frequency), imbalance of body
      (distress), moodiness (distress), being unable to move limbs at will (distress),
      shoulder pain (distress), and slower response (frequency) were independent
      factors of the total symptom burden score. These findings can provide essential
      information for efficient symptom management of patients with stroke. This trial
      was registered with the ISRCTN registry (registration number: ISRCTN18421629).

PMID- 30233064
TI  - Microbleeds in fronto-subcortical circuits are predictive of dementia conversion
      in patients with vascular cognitive impairment but no dementia.
AB  - Cerebral small vessel disease (CSVD) is a common etiology of vascular cognitive
      impairment with no dementia (V-CIND). Studies have revealed that cerebral
      microbleeds (CMBs), a feature of CSVD, contribute to cognitive impairment.
      However, the association between CMBs and dementia conversion in individuals with
      V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the
      conversion from V-CIND to dementia in CSVD patients. We recruited and
      prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated
      using a series of comprehensive neuropsychological scales, including the Chinese
      version of the Montreal Cognitive Assessment and the Clinical Dementia Rating.
      MRI assessments were used to quantify lacunar infarcts, white matter
      hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85
      patients completed the assessment for dementia conversion at a 1-year follow-up
      assessment. Multivariate logistic regression analyses were conducted to examine
      independent clinical and MRI variables associated with dementia conversion.
      Twenty-four patients (29.3%) had converted to dementia at the 1-year follow-up,
      and these individuals had significantly more CMBs in the fronto-subcortical
      circuits. Multivariate logistic regression analyses revealed that the patients
      with CMBs in the fronto-subcortical circuits (odds ratio = 4.4; 95% confidence
      interval: 1.602-12.081, P = 0.004) and 5 or more CMBs overall (odds ratio = 17.6,
      95% confidence interval: 3.23-95.84, P = 0.001) had a significantly increased
      risk of dementia at the 1-year follow-up. These findings indicate that CMBs in
      the fronto-subcortical circuits may be predictive of dementia conversion in CSVD
      patients with V-CIND, and thus extend the clinical significance of CMBs. This
      trial was registered with the Chinese Clinical Trial Registry (registration
      number: ChiCTR1800017077). Protocol version: 1.0.

PMID- 30233065
TI  - LncRNA SNHG12 ameliorates brain microvascular endothelial cell injury by
      targeting miR-199a.
AB  - Long non-coding RNAs regulate brain microvascular endothelial cell death, the
      inflammatory response and angiogenesis during and after ischemia/reperfusion and
      oxygen-glucose deprivation/reoxygenation (OGD/R) insults. The long non-coding
      RNA, SNHG12, is upregulated after ischemia/reperfusion and OGD/R in microvascular
      endothelial cells of the mouse brain. However, its role in ischemic stroke has
      not been studied. We hypothesized that SNHG12 positively regulates ischemic
      stroke, and therefore we investigated its mechanism of action. We established an
      OGD/R mouse cell model to mimic ischemic stroke by exposing brain microvascular
      endothelial cells to OGD for 0, 2, 4, 8, 16 or 24 hours and reoxygenation for 4
      hours. Quantitative real-time polymerase chain reaction showed that SNHG12 levels
      in brain microvascular endothelial cells increased with respect to OGD exposure
      time. Brain microvascular endothelial cells were transfected with pcDNA-control,
      pcDNA-SNHG12, si-control, or si-SNHG12. After exposure to OGD for 16 hours, these
      cells were then analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H
      tetrazolium bromide, trypan blue exclusion, western blot, and capillary-like tube
      formation assays. Overexpression of SNHG12 inhibited brain microvascular
      endothelial cell death and the inflammatory response but promoted angiogenesis
      after OGD/R, while SNHG12 knockdown had the opposite effects. miR-199a was
      identified as a target of SNHG12, and SNHG12 overexpression reversed the effect
      of miR-199a on brain microvascular endothelial cell death, the inflammatory
      response, and angiogenesis. These findings suggest that SNHG12 suppresses
      endothelial cell injury induced by OGD/R by targeting miR-199a.

PMID- 30233066
TI  - Molecular mechanism of panaxydol on promoting axonal growth in PC12 cells.
AB  - Nerve growth factor (NGF) promotes axonal growth in PC12 cells primarily by
      regulating the RTK-RAS-MEK-ERK pathway. Panaxydol, a polyacetylene isolated from
      Panax notoginseng, can mimic the effects of NGF. Panaxydol promotes neurite
      outgrowth in PC12 cells, but its molecular mechanism remains unclear. Indeed,
      although alkynol compounds such as panaxydol can increase intracellular cyclic
      adenosine 3',5'-monophosphate (cAMP) levels and the ERK inhibitor U0126 inhibits
      alkynol-induced axonal growth, how pathways downstream of cAMP activate ERK have
      not been investigated. This study observed the molecular mechanism of panaxydol-,
      NGF- and forskolin-induced PC12 cell axon growth using specific signaling pathway
      inhibitors. The results demonstrated that although the RTK inhibitor SU5416
      obviously inhibited the growth-promoting effect of NGF, it could not inhibit the
      promoting effect of panaxydol on axonal growth of PC12 cells. The adenylate
      cyclase inhibitor SQ22536 and cAMP-dependent protein kinase inhibitor RpcAMPS
      could suppress the promoting effect of forskolin and panaxydol on axonal growth.
      The ERK inhibitor U0126 inhibited axonal growth induced by all three factors.
      However, the PKA inhibitor H89 inhibited the promoting effect of forskolin on
      axonal growth but could not suppress the promoting effect of panaxydol. A western
      blot assay was used to determine the effects of stimulating factors and
      inhibitors on ERK phosphorylation levels. The results revealed that NGF activates
      the ERK pathway through tyrosine receptors to induce axonal growth of PC12 cells.
      In contrast, panaxydol and forskolin increased cellular cAMP levels and were
      inhibited by adenylyl cyclase inhibitors. The protein kinase A inhibitor H89
      completely inhibited forskolin-induced axonal outgrowth and ERK phosphorylation,
      but could not inhibit panaxydol-induced axonal growth and ERK phosphorylation.
      These results indicated that panaxydol promoted axonal growth of PC12 cells
      through different pathways downstream of cAMP. Considering that exchange protein
      directly activated by cAMP 1 (Epac1) plays an important role in mediating cAMP
      signaling pathways, RNA interference experiments targeting the Epac1 gene were
      employed. The results verified that Epac1 could mediate the axonal growth
      signaling pathway induced by panaxydol. These findings suggest that compared with
      NGF and forskolin, panaxydol elicits axonal growth through the cAMP-Epac1-Rap1
      MEK-ERK-CREB pathway, which is independent of PKA.

PMID- 30233067
TI  - Translocator protein ligand, YL-IPA08, attenuates lipopolysaccharide-induced
      depression-like behavior by promoting neural regeneration.
AB  - Translocator protein has received attention for its involvement in the
      pathogenesis of depression. This study assessed the effects of the new
      translocator protein ligand, YL-IPA08, on alleviating inflammation-induced
      depression-like behavior in mice and investigated its mechanism of action. Mice
      were intracerebroventricularly injected with 1, 10, 100 or 1000 ng
      lipopolysaccharide. The tail-suspension test and the forced swimming test
      confirmed that 100 ng lipopolysaccharide induced depression-like behavior. A
      mouse model was then established by intraventricular injection of 100 ng
      lipopolysaccharide. On days 16-24 after model establishment, mice were
      intragastrically administered 3 mg/kg YL-IPA08 daily. Immunohistochemistry was
      used to determine BrdU and NeuN expression in the hippocampus. YL-IPA08
      effectively reversed the depression-like behavior of lipopolysaccharide-treated
      mice, restored body mass, increased the number of BrdU-positive cells, and the
      number and proportion of BrdU and NeuN double-positive cells. These findings
      indicate that YL-IPA08 can attenuate lipopolysaccharide-induced depression-like
      behavior in mice by promoting the formation of hippocampal neurons.

PMID- 30233068
TI  - Glial fibrillary acidic protein levels are associated with global histone H4
      acetylation after spinal cord injury in rats.
AB  - Emerging evidence has suggested global histone H4 acetylation status plays an
      important role in neural plasticity. For instance, the imbalance of this
      epigenetic marker has been hypothesized as a key factor for the development and
      progression of several neurological diseases. Likewise, astrocytic reactivity - a
      well-known process that markedly influences the tissue remodeling after a central
      nervous system injury - is crucial for tissue remodeling after spinal cord injury
      (SCI). However, the linkage between the above-mentioned mechanisms after SCI
      remains poorly understood. We sought to investigate the relation between both
      glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B)
      (astrocytic reactivity classical markers) and global histone H4 acetylation
      levels. Sixty-one male Wistar rats (aged ~3 months) were divided into the
      following groups: sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI;
      72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not
      S100B was associated with global histone H4 acetylation levels. Moreover, global
      histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing
      at least three clearly defined phases (first phase: no changes in the 6, 24 and
      48 hours post-SCI groups; second phase: increased levels in the 72 hours post-SCI
      group; and a third phase: return to levels similar to control in the 7 days post
      SCI group). Overall, these findings suggest global H4 acetylation levels exhibit
      distinct patterns of expression during the first week post-SCI, which may be
      associated with GFAP levels in the perilesional tissue. Current data encourage
      studies using H4 acetylation as a possible biomarker for tissue remodeling after
      spinal cord injury.

PMID- 30233069
TI  - A rapid micro-magnetic resonance imaging scanning for three-dimensional
      reconstruction of peripheral nerve fascicles.
AB  - The most common methods for three-dimensional reconstruction of peripheral nerve
      fascicles include histological and radiology techniques. Histological techniques
      have many drawbacks including an enormous manual workload and poor image
      registration. Micro-magnetic resonance imaging (Micro-MRI), an emerging radiology
      technique, has been used to report results in the brain, liver and tumor tissues.
      However, micro-MRI usage for obtaining intraneural structures has not been
      reported. The aim of this study was to present a new imaging method for three
      dimensional reconstruction of peripheral nerve fascicles by 1T micro-MRI. Freshly
      harvested sciatic nerve samples from an amputated limb were divided into four
      groups. Two different scanning conditions (Mannerist Solution/GD-DTPA contrast
      agent, distilled water) were selected, and both T1 and T2 phases programmed for
      each scanning condition. Three clinical surgeons evaluated the quality of the
      images via a standardized scale. Moreover, to analyze deformation of the two
      dimensional image, the nerve diameter and total area of the micro-MRI images were
      compared after hematoxylin-eosin staining. The results show that rapid micro-MRI
      imaging method can be used for three-dimensional reconstruction of the fascicle
      structure. Nerve sample immersed in contrast agent (Mannerist Solution/GD-DTPA)
      and scanned in the T1 phase was the best. Moreover, the nerve sample was scanned
      freshly and can be recycled for other procedures. MRI images show better
      stability and smaller deformation compared with histological images. In
      conclusion, micro-MRI provides a feasible and rapid method for three-dimensional
      reconstruction of peripheral nerve fascicles, which can clearly show the internal
      structure of the peripheral nerve.

PMID- 30233070
TI  - Microencapsulated Schwann cell transplantation inhibits P2X3 receptor expression
      in dorsal root ganglia and neuropathic pain.
AB  - Schwann cell transplantation is a promising method to promote neural repair, and
      can be used for peripheral nerve protection and myelination. Microcapsule
      technology largely mitigates immune rejection of transplanted cells. We
      previously showed that microencapsulated olfactory ensheathing cells can reduce
      neuropathic pain and we hypothesized that microencapsulated Schwann cells can
      also inhibit neuropathic pain. Rat Schwann cells were cultured by subculture and
      then microencapsulated and were tested using a rat chronic constriction injury
      (CCI) neuropathic pain model. CCI rats were treated with Schwann cells or
      microencapsulated Schwann cells and were compared with sham and CCI groups.
      Mechanical withdrawal threshold and thermal withdrawal latency were assessed
      preoperatively and at 1, 3, 5, 7, 9, 11 and 14 days postoperatively. The
      expression of P2X3 receptors in L4-5 dorsal root ganglia of the different groups
      was detected by double-label immunofluorescence on day 14 after surgery. Compared
      with the chronic constriction injury group, mechanical withdrawal threshold and
      thermal withdrawal latency were higher, but the expression of P2X3 receptors was
      remarkably decreased in rats treated with Schwann cells and microencapsulated
      Schwann cells, especially in the rats transplanted with microencapsulated Schwann
      cells. The above data show that microencapsulated Schwann cell transplantation
      inhibits P2X3 receptor expression in L4-5 dorsal root ganglia and neuropathic
      pain.

PMID- 30233071
TI  - Total brachial plexus injury: contralateral C7 root transfer to the lower trunk
      versus the median nerve.
AB  - Contralateral C7 (cC7) root transfer to the healthy side is the main method for
      the treatment of brachial plexus root injury. A relatively new modification of
      this method involves cC7 root transfer to the lower trunk via the prespinal
      route. In the current study, we examined the effectiveness of this method using
      electrophysiological and histological analyses. To this end, we used a rat model
      of total brachial plexus injury, and cC7 root transfer was performed to either
      the lower trunk via the prespinal route or the median nerve via a subcutaneous
      tunnel to repair the injury. At 4, 8 and 12 weeks, the grasping test was used to
      measure the changes in grasp strength of the injured forepaw.
      Electrophysiological changes were examined in the flexor digitorum superficialis
      muscle. The change in the wet weight of the forearm flexor was also measured.
      Atrophy of the flexor digitorum superficialis muscle was assessed by hematoxylin
      eosin staining. Toluidine blue staining was used to count the number of
      myelinated nerve fibers in the injured nerves. Compared with the traditional
      method, cC7 root transfer to the lower trunk via the prespinal route increased
      grasp strength of the injured forepaw, increased the compound muscle action
      potential maximum amplitude, shortened latency, substantially restored tetanic
      contraction of the forearm flexor muscles, increased the wet weight of the
      muscle, reduced atrophy of the flexor digitorum superficialis muscle, and
      increased the number of myelinated nerve fibers. These findings demonstrate that
      for finger flexion functional recovery in rats with total brachial plexus injury,
      transfer of the cC7 root to the lower trunk via the prespinal route is more
      effective than transfer to the median nerve via subcutaneous tunnel.

PMID- 30233072
TI  - Hyperoside protects the blood-brain barrier from neurotoxicity of amyloid beta 1
      42.
AB  - Mounting evidence indicates that amyloid beta protein (Abeta) exerts
      neurotoxicity by disrupting the blood-brain barrier (BBB) in Alzheimer's disease.
      Hyperoside has neuroprotective effects both in vitro and in vivo against Abeta.
      Our previous study found that hyperoside suppressed Abeta1-42-induced leakage of
      the BBB, however, the mechanism remains unclear. In this study, bEnd.3 cells were
      pretreated with 50, 200, or 500 uM hyperoside for 2 hours, and then exposed to
      Abeta1-42 for 24 hours. Cell viability was determined using 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Flow cytometry and
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay were
      used to analyze cell apoptosis. Western blot assay was carried out to analyze
      expression levels of Bax, Bcl-2, cytochrome c, caspase-3, caspse-8, caspase-9,
      caspase-12, occludin, claudin-5, zonula occludens-1, matrix metalloproteinase-2
      (MMP-2), and MMP-9. Exposure to Abeta1-42 alone remarkably induced bEnd.3 cell
      apoptosis; increased ratios of cleaved caspase-9/caspase-9, Bax/Bcl-2, cleaved
      caspase-8/caspase-8, and cleaved caspase-12/caspase-12; increased expression of
      cytochrome c and activity of caspase-3; diminished levels of zonula occludens-1,
      claudin-5, and occludin; and increased levels of MMP-2 and MMP-9. However,
      hyperoside pretreatment reversed these changes in a dose-dependent manner. Our
      findings confirm that hyperoside alleviates fibrillar Abeta1-42-induced BBB
      disruption, thus offering a feasible therapeutic application in Alzheimer's
      disease.

PMID- 30233073
TI  - Achyranthes bidentata polypeptide protects dopaminergic neurons from apoptosis
      induced by rotenone and 6-hydroxydopamine.
AB  - It has been well documented that Achyranthes bidentata polypeptides (ABPPs) are
      potent neuroprotective agents in several types of neurons. However, whether ABPPs
      protect dopaminergic neurons from apoptosis induced by neurotoxins is still
      unknown. This study was designed to observe the effect of ABPPk, a purified
      fraction of ABPPs, on apoptosis of dopaminergic neurons. SH-5YHY cells and
      primary dopaminergic neurons were pre-treated with ABPPk (25, 50, or 100 ng/mL)
      for 12 hours. Cells were then exposed to 6-hydroxydopamine (50 or 150 MUM) or
      rotenone (50 or 200 MUM) for 36 hours to induce cell apoptosis. Our results
      demonstrate that ABPPk markedly increased viability in SH-SY5Y cells and primary
      dopaminergic neurons, decreased lactate dehydrogenase activity and number of
      apoptotic dopaminergic neurons, elevated mitochondrial membrane potential, and
      increased Bcl-2/Bax ratio. These findings suggest that ABPPk protects
      dopaminergic neurons from apoptosis, and that ABPPk treatment might be an
      effective intervention for treating dopaminergic neuronal loss associated with
      disorders such as Parkinson's disease.

PMID- 30233074
TI  - Enriched environment elevates expression of growth associated protein-43 in the
      substantia nigra of SAMP8 mice.
AB  - An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury, but the underlying
      mechanism for this is not clear. Growth associated protein-43 (GAP-43) is closely
      associated with neurite outgrowth and axon regeneration during neural
      development. We speculate that an enriched environment can reduce damage to
      dopaminergic neurons by affecting the expression of GAP-43. This study is
      designed to test this hypothesis. Three-month-old female senescence-accelerated
      mouse prone 8 (SAMP8) mice were housed for 3 months in an enriched environment or
      a standard environment. These mice were then subcutaneously injected in the
      abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze
      testing demonstrated that learning and memory abilities were better in the
      enriched environment group than in the standard environment group. Reverse
      transcription polymerase chain reaction, immunohistochemistry and western blot
      assays showed that mRNA and protein levels of GAP-43 in the substantia nigra were
      higher after MPTP application in the enriched environment group compared with the
      standard environment group. These findings indicate that an enriched environment
      can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a
      mechanism by which an enriched environment protects against MPTP-induced neuronal
      damage.

PMID- 30233075
TI  - Cognitive deficits and Alzheimer-like neuropathological impairments during
      adolescence in a rat model of type 2 diabetes mellitus.
AB  - Numerous studies have shown that many patients who suffer from type 2 diabetes
      mellitus exhibit cognitive dysfunction and neuronal synaptic impairments.
      Therefore, growing evidence suggests that type 2 diabetes mellitus has a close
      relationship with occurrence and progression of neurodegeneration and neural
      impairment in Alzheimer's disease. However, the relationship between metabolic
      disorders caused by type 2 diabetes mellitus and neurodegeneration and neural
      impairments in Alzheimer's disease is still not fully determined. Thus, in this
      study, we replicated a type 2 diabetic animal model by subcutaneous injection of
      newborn Sprague-Dawley rats with monosodium glutamate during the neonatal period.
      At 3 months old, the Barnes maze assay was performed to evaluate spatial memory
      function. Microelectrodes were used to measure electrophysiological function in
      the hippocampal CA1 region. Western blot assay was used to determine expression
      levels of glutamate ionotropic receptor NMDA type subunit 2A (GluN2A) and GluN2B
      in the hippocampus. Enzyme-linked immunosorbent assay was used to determine
      levels of interleukin-1beta, tumor necrosis factor alpha, and interleukin-6 in
      the hippocampus and cerebral cortex, as well as hippocampal amyloid beta (Abeta)1
      40 and Abeta1-42 levels. Our results showed that in the rat model of type 2
      diabetes mellitus caused by monosodium glutamate exposure during the neonatal
      period, latency was prolonged and the number of errors increased in the Barnes
      maze. Further, latency was increased and time in the escape platform quadrant
      shortened. Number of times crossing the platform was also reduced in the Morris
      water maze. After high frequency stimulation of the hippocampus, synaptic
      transmission was inhibited, expression of GluN2A and GluN2B were decreased in the
      hippocampus, expression of interleukin 1beta, interleukin 6, and tumor necrosis
      factor alpha was increased in the hippocampus and cortex, and levels of Abeta1-40
      and Abeta1-42 were increased in the hippocampus. These findings confirm that type
      2 diabetes mellitus induced by neonatal monosodium glutamate exposure results in
      Alzheimer-like neuropathological changes and further causes cognitive deficits
      and neurodegeneration in young adulthood.

PMID- 30233076
TI  - SIRT1 facilitates amyloid beta peptide degradation by upregulating lysosome
      number in primary astrocytes.
AB  - Previous studies have shown that sirtuin 1 (SIRT1) reduces the production of
      neuronal amyloid beta (Abeta) and inhibits the inflammatory response of glial
      cells, thereby generating a neuroprotective effect against Abeta neurotoxicity in
      animal models of Alzheimer's disease. However, the protective effect of SIRT1 on
      astrocytes is still under investigation. This study established a time point
      model for the clearance of Abeta in primary astrocytes. Results showed that 12
      hours of culture was sufficient for endocytosis of oligomeric Abeta, and 36 hours
      sufficient for effective degradation. Immunofluorescence demonstrated that Abeta
      degradation in primary astrocytes relies on lysosome function. Enzymatic agonists
      or SIRT1 inhibitors were used to stimulate cells over a concentration gradient.
      Abeta was co-cultured for 36 hours in medium. Western blot assay results under
      different conditions revealed that SIRT1 relies on its deacetylase activity to
      promote intracellular Abeta degradation. The experiment further screened SIRT1
      using quantitative proteomics to investigate downstream, differentially expressed
      proteins in the Abeta degradation pathway and selected the ones related to enzyme
      activity of SIRT1. Most of the differentially expressed proteins detected are
      close to the primary astrocyte lysosomal pathway. Immunofluorescence staining
      demonstrated that SIRT1 relies on its deacetylase activity to upregulate lysosome
      number in primary astrocytes. Taken together, these findings confirm that SIRT1
      relies on its deacetylase activity to upregulate lysosome number, thereby
      facilitating oligomeric Abeta degradation in primary astrocytes.

PMID- 30233079
TI  - Abstracts of 8th Conjoint Ophthalmology Scientific Conference in conjunction with
      10th UKM Ophthalmology Symposium.

PMID- 30233077
TI  - Taurine protects against retinal and optic nerve damage induced by endothelin-1
      in rats via antioxidant effects.
AB  - Endothelin-1 (ET-1), a potent vasoconstrictor, is involved in retinal vascular
      dysregulation and oxidative stress in glaucomatous eyes. Taurine (TAU), a
      naturally occurring free amino acid, is known for its neuroprotective and
      antioxidant properties. Hence, we evaluated its neuroprotective properties
      against ET-1 induced retinal and optic nerve damage. ET-1 was administered
      intravitreally to Sprague-Dawley rats and TAU was injected as pre-, co- or post
      treatment. Animals were euthanized seven days post TAU injection. Retinae and
      optic nerve were examined for morphology, and were also processed for caspase-3
      immunostaining. Retinal redox status was estimated by measuring retinal
      superoxide dismutase, catalase, glutathione, and malondialdehyde levels using
      enzyme-linked immuosorbent assay. Histopathological examination showed
      significantly improved retinal and optic nerve morphology in TAU-treated groups.
      Morphometric examination showed that TAU pre-treatment provided marked protection
      against ET-1 induced damage to retina and optic nerve. In accordance with the
      morphological observations, immunostaining for caspase showed a significantly
      lesser number of apoptotic retinal cells in the TAU pre-treatment group. The
      retinal oxidative stress was reduced in all TAU-treated groups, and particularly
      in the pre-treatment group. The findings suggest that treatment with TAU,
      particularly pre-treatment, prevents apoptosis of retinal cells induced by ET-1
      and hence prevents the changes in the morphology of retina and optic nerve. The
      protective effect of TAU against ET-1 induced retinal and optic nerve damage is
      associated with reduced retinal oxidative stress.

PMID- 30233078
TI  - Restoration of an injured lower dorsal ascending reticular activating system in a
      patient with intraventricular hemorrhage.

PMID- 30233080
TI  - Thrombosis of atypical location: how to treat patients in the era of direct oral
      anticoagulants?
AB  - In 4% of cases, venous thromboembolism (VTE) involves organ-related venous
      territories such as splanchnic, renal, gonadal, and cerebral venous segments, and
      is often called venous thromboembolism of atypical location (VTE-AL).
      Recommendations regarding the method, intensity, and duration of anticoagulant
      therapy for VTE-AL are not well established. Direct oral anticoagulants (DOACs)
      have been a promising alternative to vitamin K antagonists in the treatment of
      acute VTE. However, all major clinical trials on DOACs excluded patients with VTE
      AL. Therefore, data on the use of DOACs in patients with VTE-AL are still limited
      to case reports and small clinical series, with a relative predominance of
      publications on splanchnic vein thrombosis including mesenteric, splenic, portal,
      and hepatic vein thrombosis. The only randomized clinical trial comparing a
      clinical outcome of patients with acute portal vein thrombosis randomized to
      either rivaroxaban or warfarin treatment yielded significantly impaired results
      due to the use of an atypical rivaroxaban dose. A prospective registration of
      clinical outcome for DOACs used in patients with VTE-AL, in those with VTE of
      typical location, and in those with VTE-AL treated with enoxaparin showed similar
      VTE recurrence and major bleeding rates in all 3 groups. High cancer prevalence,
      typical for VTE-AL, significantly impacted survival as well as VTE recurrence
      rates and major bleeding outcomes in this study. In general, although still
      limited, the results for DOAC use in VTE-AL are encouraging and we do not
      hesitate to use DOACs, particularly rivaroxaban or apixaban, in selected patients
      with VTE-AL.

PMID- 30233081
TI  - Pneumothorax in a young nonsmoking patient: a manifestation of Langerhans cell
      histiocytosis.

PMID- 30233082
TI  - miR-126 Suppresses Invasion and Migration of Malignant Glioma by Targeting Mature
      T Cell Proliferation 1 (MTCP1).
AB  - BACKGROUND The aim of this study was to assess the utility of miR-126 in
      promoting malignant glioma progression and determine if miR-126 might be a target
      for malignant glioma treatment. MATERIAL AND METHODS The expression of miR-126 in
      malignant glioma tissues and cells was detected by reverse transcription
      polymerase chain reaction (RT-PCR). Western blot analysis was used to detect
      changes in protein levels. Transwell assay was applied to assess the migration
      and invasion in vitro. Luciferase reporter assay was used to confirm the binding
      of miR-126 and mature T cell proliferation 1 (MTCP1). A nude mouse tumor model
      was used to assess the molecular mechanism in vivo. RESULTS The expression level
      of miR-126 in patients with stage III~IV malignant glioma was significant lower
      than that in patients with stage I~II. In different malignant glioma cell lines,
      the expression was significantly reduced in U87MG. Compared with the control
      mimics group, the expression of MTCP1 was significantly decreased. The results of
      Transwell assay showed that the invasiveness and migration in the miR-126 mimics
      group was significantly lower than in the control mimics groups. miR-126 mimics
      did not affect luciferase activity in the Mut-miR-126/MTCP1 group, while miR-126
      mimics reduced luciferase activity by 54% in the Wt-miR-126/MTCP1 group. The
      results of invasion showed that the invasion ability in the miR-126 inhibitor
      group was significantly increased compared with that in the normal control (NC)
      group, while the invasion and migration abilities in the MTCP1 siRNA group were
      significantly increased. After 6 weeks, the tumor volume in the miR-126 inhibitor
      group was significantly increased, while that in the MTCP1 siRNA group was
      significantly decreased. CONCLUSIONS miR-126 inhibits the migration of malignant
      glioma cells by inhibiting MTCP1.

PMID- 30233083
TI  - Correction: Report of the inaugural Interferon Research Summit: interferon in
      inflammatory diseases.
AB  - [This corrects the article DOI: 10.1136/lupus-2018-000276.].

PMID- 30233084
TI  - Iodine deficiency and its associated factors among primary school children in
      Anchar district, Eastern Ethiopia.
AB  - Background: Iodine deficiency is a major public health problem in Ethiopia. Most
      of the studies in Ethiopia were done on clinical goiter without assessing the
      subclinical iodine deficiency. Therefore, there was a need to study the magnitude
      and associated factors of iodine deficiency among school-age children in Eastern
      Ethiopia. Subjects and methods: A school-based cross-sectional study design was
      used to assess the iodine level of 200 primary school children aged 6-12 years
      who were selected by using the multistage sampling technique. The study used an
      interview-administered questionnaire and checklists to collect data from the
      respondents. Data were entered to EpiData version 3.1 and exported to SPSS
      version 22.0 for analysis. Bivariable and multivariable analyses were conducted,
      and statistical significance was declared at p value <=0.05. Results: The median
      urinary iodine concentration of the children was 146 ug/L, and 31% had median
      urinary iodine concentration below the acceptable level (<100 ug/L). Female sex
      (adjusted odds ratio [AOR]=3.12, 95% CI: 1.52, 6.39), family size >=5 (AOR=2.24,
      95% CI: 1.06, 4.75), having no awareness of a balanced diet (AOR=3.25, 95% CI:
      1.37, 7.71), and cabbage consumption >=2 times per week (AOR=3.01, 95% CI: 1.31,
      6.93) were the significant associated factors. Conclusion and recommendation:
      Ethiopia is implementing the universal iodization of salt. However, urinary
      iodine deficiency and utilization of inadequately iodized salt were high in the
      study area. Therefore, the health sectors of the study site should disseminate
      messages to increase the awareness on iodized salt, iodine-rich foods, and
      goiterogens.

PMID- 30233085
TI  - Would You Encourage Your Child to Follow in Your Footsteps and Become a
      Physician?

PMID- 30233086
TI  - I Remain an Unabashed Cheerleader for Our Children Choosing Medicine as a Career.

PMID- 30233088
TI  - Missouri is Last in the Nation Without a Prescription Drug Monitoring Program
      Bill: Will the Bill Pass This Year?

PMID- 30233087
TI  - I'm Glad I Was Encouraged to Become a Physician: I'm 'Shifting' Into Emergency
      Medicine Very Nicely...

PMID- 30233089
TI  - "I Stuffed Their Mouths With Gold": How Hospitals Destroyed the Private Practice
      of Internal Medicine.

PMID- 30233090
TI  - Celebrating 125 Years of the Osteopathic Profession.

PMID- 30233092
TI  - MSMA Members in the News.

PMID- 30233091
TI  - Contributors to the MPHP 2016 Fund Raising Campaign.

PMID- 30233094
TI  - 159th Annual Convention March 31-April 2, 2017 | Sheraton Kansas City Hotel at
      Crown Center | Kansas City, MO www.msma.org/annual-convention.

PMID- 30233093
TI  - Cover to Cover.

PMID- 30233095
TI  - 159th Annual Convention General Sessions & Events.

PMID- 30233097
TI  - The Ever-Changing Field of Physical Medicine and Rehabilitation.

PMID- 30233096
TI  - Direct-to-Consumer Genomics: Harmful or Empowering?: It is important to stress
      that genetic risk is not the same as genetic destiny.
AB  - The price of whole-genome sequencing is now within the budget of the average
      American consumer. This has resulted in the commercialization of genome
      sequencing for a variety of applications, including health-related risk
      assessment. Direct-to-consumer marketing of personal DNA sequence information
      uncouples the generation of personal health-related data from the physician
      patient relationship. Here, I discuss the status of consumer genomics and the
      current and potential concerns about bypassing physicians in the analysis and
      interpretation of personal genomic information and subsequent health care
      decision-making.

PMID- 30233098
TI  - "Put Me Back In, Coach!" Concussion and Return to Play.
AB  - Concussion is a mild traumatic brain injury (TBI) sustained as a result of blunt
      force or acceleration/deceleration injury to the head.1,2 Approximately 1.4-3.8
      million concussions occur each year in the United States, making the
      understanding of concussion pathophysiology and how it can impact one's gross
      function an essential part of a physician's toolbelt.3,4 It is important to
      recognize that the biochemical changes of concussion that result in functional
      cognitive deficits and compromised synaptic plasticity are greatest at three days
      and still active more than 15 days post-injury.6,7 Therefore, prompt diagnosis of
      concussion and subsequent proper treatment can help promote adequate healing and
      prevent synergistic effects of second-impact syndrome. Recognition of the common
      signs and symptoms of concussion combined with pertinent physical examination
      findings, concussion assessment tools aid with proper identification and triage
      of patients. Consensus guidelines have delineated return to play protocol and
      treatment regimen for these patients and athletes. The goal of treatment for
      concussion is important to limit long-term deleterious effects that can result
      from single or multiple injuries to the brain.

PMID- 30233099
TI  - Stroke Rehabilitation: Current American Stroke Association Guidelines, Care, and
      Implications for Practice.
AB  - Stroke attacked approximately 795,000 Americans last year, and it was the fifth
      leading cause of death in the United States. In 2016, the American Stroke
      Association published updated guidelines for stroke rehabilitation, with
      recommendations intended to improve systems of care and functional outcomes for
      people who suffer stroke and important recommendations regarding specific aspects
      of care. This article summarizes some of these recommendations with implications
      for those who treat stroke patients in their practices.

PMID- 30233100
TI  - The Changing Face of Spine Care: The MU Comprehensive Spine Center.
AB  - Back pain is extraordinarily common, and the current approach to treatment has
      yielded enormous financial burdens on health care systems and society in general.
      In addition, primary care providers and patients alike are often unsure where to
      seek further care, and what, if any, advanced tests or images are needed. As a
      result, spine surgeons often see a high percentage of non-operative patients when
      unnecessary, redundant, or incorrect imaging was obtained. At MU Health Care a
      team of physiatrists, orthopedic surgeons, neurosurgeons sought to address these
      issues by forming the MU Comprehensive Spine Center that offers a systematic,
      collaborative approach to spine care.

PMID- 30233101
TI  - Advances in the Treatment of Chronic Pelvic Pain: A Multidisciplinary Approach to
      Treatment.
AB  - The treatment of chronic pelvic pain can often be difficult, as many times after
      visits to multiple providers, patients can carry multiple diagnoses. Even with
      appropriate treatments, patients often have continued pain that can result in
      frustrations for both patients and their providers. Utilizing a multidisciplinary
      and multimodal approach to chronic pelvic pain is beneficial, especially when
      including evaluation for musculoskeletal dysfunction or other contributors to
      chronic pelvic pain.

PMID- 30233102
TI  - Problem-Solving in Patients with Targeted Drug Delivery Systems.
AB  - Patients with intrathecal drug delivery systems presenting for after-hours care
      typically cause angst among physicians staffing emergency rooms and urgent care
      centers. The chief complaint of "my pump isn't working" leaves physicians
      inexperienced with these devices in a defensive position. Fortunately, pump
      malfunctions are rare. Resources are available to help physicians work through
      patient concerns. These resources include algorithms to manage possible over- or
      under-infusion of the various drugs used in these systems as well as technical
      support from pump manufacturers.

PMID- 30233103
TI  - Changing Payment Models: Shifting Focus on Post Acute Care.

PMID- 30233104
TI  - Beware of the Film Findings!: Low Back Pain Patients and Healthy Volunteers Have
      A Similar X-Ray Appearance.
AB  - Low back pain (LBP) affects 20 to 30% of the United States general population,
      making it the fifth most common reason for all physician visits in the U.S. The
      resultant financial burden on the U.S. health care industry continues to rise
      each year with recent estimates of over $80 billion spent annually. However,
      despite the dramatic rise in health care utilization and costs for this
      complaint, self-reported outcomes have not improved. The radiographic analysis of
      a healthy asymptomatic population vs. a cohort of LBP patients with lumbar
      degenerative disc disease, specifically as it relates to posture, spinal
      alignments, including lumbar lordosis, as well as other findings, may provide
      insight to more effectively care for the LBP patient and, in return, possibly
      help to rein in related health care costs.

PMID- 30233105
TI  - Epidemiology of Women's Flat Track Roller Derby Injuries in Kansas City.
AB  - This cross-sectional descriptive retrospective epidemiological pilot study
      determined the frequency, circumstances, type, and outcome of injuries in the
      members of a Kansas City women's flat track roller derby league. Injuries were
      reported by 79% of the respondents, with 50% having sustained multiple injuries.
      Medical attention was required by 64%. The risk of injury in the sport is high.
      Further study is needed to identify specific factors that can be modified to
      decrease the injury rate.

PMID- 30233106
TI  - Barriers and Benefits of EHR Usage in Missouri: A Five-Year Journey.

PMID- 30233107
TI  - Fate of pyrazines in the flavored liquids of e-cigarettes.
AB  - Popularity of electronic cigarettes (ECIGs) has increased tremendously among
      young people, in part due to flavoring additives in ECIG liquids. Pyrazines are
      an important class of these additives, and their presence in tobacco cigarettes
      has been correlated with increased acceptability of smoking among smokers and
      bystanders. Pyrazine use by the tobacco industry is therefore thought to
      encourage smoking. However, the extent of transfer of pyrazines present in the
      liquid to aerosols upon vaping remains unclear. We present a simple analytical
      method to quantify six pyrazine derivatives in liquids and aerosols of ECIGs that
      allows the isolation of pyrazines from interfering compounds, like nicotine.
      Standard pyrazine solutions and commercial ECIG samples of different brands and
      flavors were tested for their pyrazine content in the liquids and in the
      generated aerosols from these solutions. Testing on ECIG commercial liquids
      revealed a heterogeneous distribution in the levels and types of pyrazines, with
      acetyl and alkyl pyrazines present in more than 70% of the samples. This method
      confirmed that pyrazine additives are common in ECIG and that labels do not
      usually reflect the type and quantity of pyrazines in the liquid. Pyrazines were
      not correlated with the nicotine content or the brand of the liquid. The aerosols
      showed similar pyrazine profiles to their corresponding liquids. The efficiency
      of transfer of pyrazines into the particle phase was approximately 46%.
      Therefore, addition of pyrazines to ECIGs should be regulated, because they act
      synergistically with nicotine to increase product appeal, ease smoking
      initiation, and discourage cessation.

PMID- 30233108
TI  - A Transportation Lp Distance for Signal Analysis.
AB  - Transport based distances, such as the Wasserstein distance and earth
      mover'sdistance, have been shown to be an effective tool in signal and image
      analysis. The success of transport based distances is in part due to their
      Lagrangian nature which allows it to capture the important variations in many
      signal classes. However these distances require the signal to be nonnegative and
      normalized. Furthermore, the signals are considered as measures and compared by
      redistributing (transporting) them, which does not directly take into account the
      signal intensity. Here we study a transport-based distance, called the TLp
      distance, that combines Lagrangian and intensity modelling and is directly
      applicable to general, non-positive and multi-channelled signals. The distance
      can be computed by existing numerical methods. We give an overview of the basic
      properties of this distance and applications to classification, with multi
      channelled non-positive one-dimensional signals and two-dimensional images, and
      color transfer.

PMID- 30233109
TI  - Multimodal Therapy: Holistic Approach.

PMID- 30233110
TI  - Yoga as an Integrative Approach for Prevention and Treatment of Oral Cancer.
AB  - Despite tremendous advancements in medicine, the number of oral cancer cases
      continues to increase, and the need for integrating alternate medicine or
      adopting an integrative approach has become a compelling cost-effective
      requirement for the management and treatment of diseases. Conventional treatment
      of oral cancer involves surgery followed by radiotherapy with or without
      chemotherapy which causes several complications including poor quality of life
      and high chances of recurrence of cancer. Oral cancer is often linked with
      obesity which is major risk factors in other cancers. Apart from obesity, oral
      cancer is thought to have an inverse relation with neurodegenerative disorders
      presumably because cell death decreases in the former case and increases in the
      latter. Ancient mind-body techniques such as yoga have not been adequately tested
      as a tool to synergize the cellular equilibrium pertaining to the treatment of
      oral cancer. Nerve growth factor (NGF), tumor necrosis factor-alpha (TNF-alpha),
      and interleukin-6 (IL-6) are among the early experimental cellular biomarkers
      that may be used to probe the modulation of oral cancer, obesity, and
      neurodegenerative disorders. Yoga has been reported to influence these molecules
      in healthy individuals but whether their expression can be altered in patients of
      oral cancer by yoga intervention is the subject of this research being discussed
      in this review article. Therefore, the present article not only reviews the
      current status of research studies in oral cancer, obesity, and neurodegenerative
      disorders but also how these are linked to each other and why the investigations
      of the putative NGF pathway, involving TNF-alpha and IL-6, could provide useful
      clues to understand the molecular effects brought about by yoga intervention in
      such patients.

PMID- 30233111
TI  - Implication of Asana, Pranayama and Meditation on Telomere Stability.
AB  - Telomeres, the repetitive sequences that protect the ends of chromosomes, help to
      maintain genomic integrity and are of key importance to human health. Telomeres
      progressively shorten throughout life and a number of studies have shown shorter
      telomere length to be associated with lifestyle disorders. Previous studies also
      indicate that yoga and lifestyle-based intervention have significant role on
      oxidative DNA damage and cellular aging. However, very few publications
      investigate telomere stability and its implication from the point of view of
      asana, pranayama, and meditation. In this context, a review was conducted to
      systematically assess the available data on the effectiveness of asana,
      pranayama, and meditation in maintaining telomere and telomerase. Literature
      search was performed using the following electronic databases: Cochrane Library,
      NCBI, PubMed, Google Scholar, EMBASE, and Web of Science. We explored the
      possible mechanisms of how asana, pranayama, and meditation might be affecting
      telomere length and telomerase. Moreover, results showed that asana and pranayama
      increase the oxygen flow to the cells and meditation reduces the stress level by
      modulating the hypothalamic-pituitary-adrenal axis. Summing up the result, it can
      be concluded that practice of asana, pranayama, and meditation can help to
      maintain genomic integrity and are of key importance to human health and
      lifestyle disorders.

PMID- 30233112
TI  - Oxygen Consumption during Viniyoga Practice in Adults.
AB  - Context: The purpose of this study was to measure the oxygen consumption (VO2)
      during Viniyoga yoga movements (asanas) and to compare VO2 walking among adults.
      Methods: Yoga practitioners (n = 10) were recruited to measure VO2 while at rest
      (30 min), practicing yoga (16 movements with different variations), and treadmill
      walking at 2 mph (10 min) and 3 mph (10 min). VO2 was measured using a whole-room
      indirect calorimetry. Each yoga movement was categorized by body orientation as
      standing, lying, and sitting. The differences in VO2 between yoga and walking
      were examined using Pearson's correlations. Differences in VO2 between poses
      (standing, sitting, and lying) were examined using linear regression models. VO2.
      Results: Mean yoga-VO2 for the entire yoga session was 3.7 (standard deviation
      [SD] 0.43, range: 4.4-8.9) ml/kg/min. Yoga-VO2 varied by body orientation:
      standing = 7.5 (SD = 1.5) ml/kg/min, lying = 5.3 (SD = 1.0) ml/kg/min, and
      sitting = 5.4 (SD = 1.1) ml/kg/min. After adjusting for body mass, frequency of
      yoga practice, and resting energy expenditure, female gender was negatively
      associated with mean yoga VO2 for standing (B = -112.19, P < 0.05), lying (B = 
      141.87, P < 0.05), and sitting (B = -129.96, P < 0.05). Mean VO2 for walking 2
      mph was comparable with sitting (r = 0.836, P < 0.05) and lying (r = 0.735, P <
      0.05) whereas walking at 3 mph was comparable with standing (r = 0.718, P < 0.05)
      and sitting (r = 0.760, P < 0.05). Conclusion: We conclude that VO2 during yoga
      practice is comparable to VO2 during slow treadmill walking and may vary based on
      gender and body orientation.

PMID- 30233113
TI  - Musculoskeletal Modeling and Analysis of Trikonasana.
AB  - Context: Yoga has origins speculated to date back to pre-Vedic Indian period and
      is practiced as a common exercise, both in India as well as all around the world.
      Although the yoga practices are ages old, there is not much research literature
      available. Moreover, with the advancement in technology, the modern analysis
      tools are not used up to their full potential. Aims: This research focuses on
      developing a framework for analyzing trikonasana, using the optical motion
      capture system, and validating the noninvasive method for analyzing muscle
      activity in prominent muscles while performing trikonasana. Subjects and Methods:
      We have adopted the noninvasive analysis method using optical motion capture
      system OptiTrackTM for recording the human motion and musculoskeletal modeling
      software LifeModTM to analyze the muscle activity while performing trikonasana.
      Surface electromyography (sEMG) studies were performed using TrignoTM (Delsys
      Inc.) wireless sEMG sensors to validate the LifeMod simulation results pertaining
      muscle activation. Results: It was observed that the characteristics of the sEMG
      match to that of the estimated muscle tension from the architecture used in this
      study. The muscle groups such as external right obliques muscles, rectus
      abdominis of the front leg, and gluteus maximus and gluteus medius of the rear
      leg were observed to undergo major activation during an isometric contraction
      while performing trikonasana. The magnitudes of the muscle tension during the
      left bend depict a close resemblance to the muscle tension magnitudes during the
      right bend. Conclusions: The optical motion capture system and musculoskeletal
      modeling software can be used to analyze muscle activity in any yoga exercise
      noninvasively. Since the yoga exercises majorly require the practitioner to
      maintain a certain posture for a considerable duration, our approach can be used
      to find the important muscles involved and their corresponding muscle tension
      when they undergo isometric contraction.

PMID- 30233114
TI  - A Randomized Trial Comparing Effect of Yoga and Exercises on Quality of Life in
      among nursing population with Chronic Low Back Pain.
AB  - Background: Chronic low back pain (CLBP) adversely affects quality of life (QOL)
      in nursing professionals. Integrated yoga has a positive impact on CLBP. Studies
      assessing the effects of yoga on CLBP in nursing population are lacking. Aim:
      This study was conducted to evaluate the effects of integrated yoga and physical
      exercises on QOL in nurses with CLBP. Methods: A total of 88 women nurses from a
      tertiary care hospital of South India were randomized into yoga group (n = 44;
      age - 31.45 +/- 3.47 years) and physical exercise group (n = 44; age - 32.75 +/-
      3.71 years). Yoga group was intervened with integrated yoga therapy module
      practices, 1 h/day and 5 days a week for 6 weeks. Physical exercise group
      practiced a set of physical exercises for the same duration. All participants
      were assessed at baseline and after 6 weeks with the World Health Organization
      Quality of Life-brief (WHOQOL-BREF) questionnaire. Results: Data were analyzed by
      Paired-samples t-test and Independent-samples t-test for within- and between
      group comparisons, respectively, using the Statistical Package for the Social
      Sciences (SPSS). Within-group analysis for QOL revealed a significant improvement
      in physical, psychological, and social domains (except environmental domain) in
      both groups. Between-group analysis showed a higher percentage of improvement in
      yoga as compared to exercise group except environmental domain. Conclusions:
      Integrated yoga was showed improvements in physical, psychological, and social
      health domains of QOL better than physical exercises among nursing professionals
      with CLBP. There is a need to incorporate yoga as lifestyle intervention for
      nursing professionals.

PMID- 30233115
TI  - The Impact of Yoga Nidra and Seated Meditation on the Mental Health of College
      Professors.
AB  - Background: World statistics for the prevalence of anxiety and mood disorders
      shows that a great number of individuals will experience some type of anxiety or
      mood disorder at some point in their lifetime. Mind-body interventions such as
      Hatha Yoga and seated meditation have been used as a form of self-help therapy
      and it is especially useful for challenging occupations such as teachers and
      professors. Aims: In this investigation, we aimed at observing the impact of Yoga
      Nidra and seated meditation on the anxiety and depression levels of college
      professors. Materials and Methods: Sixty college professors, men and women, aged
      between 30 and 55 years were randomly allocated in one of the three experimental
      groups: Yoga Nidra, seated meditation, and control group. Professors were
      evaluated two times throughout the 3-month study period. Psychological variables
      included anxiety, stress, and depression. Results: Data analysis showed that the
      relaxation group presented better intragroup results in the anxiety levels.
      Meditation group presented better intragroup results only in the anxiety variable
      (physical component). Intergroup analysis showed that, except for the depression
      levels, both intervention groups presented better results than the control group
      in all other variables. Conclusions: Prepost results indicate that both
      interventions represent an effective therapeutic approach in reducing anxiety and
      stress levels. However, there was a tendency toward a greater effectiveness of
      the Yoga Nidra intervention regarding anxiety, which might represent an effective
      tool in reducing both cognitive and physiological symptoms of anxiety.

PMID- 30233116
TI  - Changes in Reaction Time after Yoga Bellows-type Breathing in Healthy Female
      Volunteers.
AB  - Background: Previously, yoga bellows-type breathing (bhastrika pranayama) reduced
      reaction time (RT) or reduced anticipatory responses in male participants or a
      mixed group of male and female participants. Aims: The present study as a control
      trial aimed to assess the effects of yoga bellows-type breathing on RT in females
      exclusively. Methods: The sample consisted of 25 healthy females, aged between 19
      and 32 years (group mean +/- standard deviation, 22.8 +/- 3.5 years). All of them
      had prior minimum experience of yoga including yoga bellows-type breathing of 12
      months. The RT was assessed in each participant before and after three randomized
      sessions differed in the intervention given held on three separate days. The
      sessions were (i) YOGA bellows-type breathing or bhastrika pranayama(BHK), (ii)
      Breath awareness (BAW), and (iii) Sitting quietly (CTL) as a control session. The
      duration of the intervention was 18 min, and the participants were assessed for
      RT before and after the intervention. Results: Repeated measures ANOVA, post hoc
      tests with Bonferroni adjusted showed that the time taken to obtain a correct
      response reduced significantly after 18 min of BAW (P < 0.05) and CTL (P < 0.05).
      However, no changes were seen in the RT after BHK. Conclusions: The results
      suggest that different interventions may optimize performance in tasks requiring
      attention in females compared to males.

PMID- 30233117
TI  - Development and Validation of Integrated Yoga Module for Obesity in Adolescents.
AB  - Background: Obesity is a growing global epidemic and cause of noncommunicable
      diseases. Yoga is one of the effective ways to reduce stress which is one of the
      causes of obesity. Nowadays, children in adolescent age are more prone to get
      obese due to lack of physical activity making them more sedentary. Aim: To
      identify the design and validation of Integrated Approach of Yoga Therapy Module
      (IAYTM) for obesity in adolescents. Materials and Methods: First phase - IAYTM
      for obesity was designed based on the literature review of classical texts and
      recently published research articles. Second phase - Designed IAYTM was validated
      by 16 subject matter (yoga) experts. Content-validity ratio (CVR) was analyzed
      using Lawshe's formula. Results: Yoga practices were designed for Integrated Yoga
      Module for Obesity in Adolescents. Yoga practices with CVR >=0.5 and which were
      validated by 16 yoga experts and approved in faculty group discussion were
      included in final Integrated Yoga Therapy Module. Conclusion: The yoga practices
      were designed and validated for IAYTM for obesity in adolescents.

PMID- 30233118
TI  - Effect of Yoga-Based Ocular Exercises in Lowering of Intraocular Pressure in
      Glaucoma Patients: An Affirmative Proposition.
AB  - Glaucoma is the most common cause of irreversible blindness worldwide, with >65
      million sufferers. It is incurable and the only therapeutic approach accepted
      till now is the lowering of intraocular pressure (IOP) medically and/or
      surgically. These known interventions might have many side effects and
      complications. Yoga-based interventions are now well accepted as alternative
      therapy in many chronic diseases. The effects of yoga in glaucoma, however, have
      not been studied adequately. Accommodation (the process of adjustment of optical
      power to maintain clear vision) of eyes leads to instant lowering of IOP.
      Therefore, we hypothesize that one of the yoga-based interventions, Tratak kriya,
      which includes ocular exercises might lead to lowering of IOP in glaucoma
      patients. The proposed Tratak kriya leads to contraction and relaxation of
      ciliary muscles which might increase outflow of aqueous humor. In addition, this
      yoga-based intervention might decrease stress and improve quality of life in
      glaucoma patients.

PMID- 30233119
TI  - Add-on Yoga Therapy for Social Cognition in Schizophrenia: A Pilot Study.
AB  - Background: Yoga as a mind-body therapy is useful in lifestyle-related disorders
      including neuropsychiatric disorders. In schizophrenia patients, yoga has been
      shown to significantly improve negative symptoms, functioning, and plasma
      oxytocin level. Aim: The aim of the study was to study the effect of add-on yoga
      therapy on social cognition in schizophrenia patients. Materials and Methods: In
      a single pre-post, study design, 15 schizophrenia patients stabilized on
      antipsychotic medication for 6 weeks were assessed for social cognition (theory
      of mind, facial emotion recognition, and social perception [SP]) and clinical
      symptoms (negative and positive symptoms and social disability) before and after
      twenty sessions of add-on yoga therapy. Results: There was a significant
      improvement in the social cognition composite score after 20 sessions of yoga
      (t[13] = -5.37, P <= 0.001). Clinical symptoms also reduced significantly after
      twenty sessions of yoga. Conclusion: Results are promising to integrate yoga in
      clinical practice, if proven in well-controlled clinical trials.

PMID- 30233120
TI  - Effect of Yoga-nidra on Adolescents Well-being: A Mixed Method Study.
AB  - Context: Adolescent well-being is a priority area for health-care interventions
      in the 21st century. Yoga-nidra is an ancient Indian method of enabling
      individuals to attain a positive state of deep physical, mental, and emotional
      relaxation. The practice produces a state of simultaneous relaxation and
      detachment resulting in inner awareness and release of stress on all planes of
      one's being. Aim: This mixed method study was carried out in adolescent students
      aged 13-15 years with an aim to assess effects of Yoga-nidra on various
      dimensions of well-being. Materials and Methods: Thirty-six students received
      Yoga-nidra sessions 30 min daily for 3 days in a week for 1 month. Primary
      outcome measures were happiness, perceived stress, overall quality of life, and
      psychological general well-being. These and other experiential dimensions of well
      being comprising of enthusiasm, alertness, quietude, clarity of thought, control
      over anger, self-confidence, and self-awareness were evaluated before and after
      intervention. Qualitative observations were recorded from participants, their
      teachers, and parents. Results of quantitative and qualitative methods were
      analyzed and compared. Results: Yoga-nidra intervention resulted in significant
      improvement in all primary outcome measures. Participants reported significant
      improvement in the feelings of happiness, enthusiasm, quietude, being more
      inspired and alert, active, having clarity of thought, control over anger, and
      self-confidence at the end of the study period. Mixed method design of the study
      provided cross-validation and convergence of results obtained from quantitative
      and qualitative assessment tools. Conclusion: Yoga-nidra is beneficial in
      improving multiple dimensions of adolescent well-being.

PMID- 30233121
TI  - Home-Based Yoga Program for the Patients Suffering from Malignant Lymphoma during
      Chemotherapy: A Feasibility Study.
AB  - Background: Yoga is proven beneficial in improving quality of life among breast
      cancer survivors receiving chemotherapy, but its effectiveness in lymphoma
      patients needs to be explored. As chemotherapy-induced neutropenia is very common
      among lymphoma patients, they are much prone to infections from the environment.
      Furthermore, trained yoga instructors are not available in every setting, so
      there is a need to develop home-based yoga program modules for lymphoma patients
      receiving chemotherapy. Aim: The aim of the study was to explore the feasibility
      and safety of yogic exercises among lymphoma patients during chemotherapy.
      Subjects and Methods: An interventional, single-arm prepost design study was
      conducted at a tertiary health-care center. Patients suffering from malignant
      lymphoma (18-65 years) with Eastern Cooperative Oncology Group performance status
      from 0 to 2, planned to receive chemotherapy were administered a home-based yoga
      program over a period of 2 months from the start of chemotherapy. The primary
      outcome variables were retention rate, acceptance rate, safety, and adherence.
      Health-related quality of life (HRQOL), fatigue level, overall sleep quality,
      depression, anxiety level, and pain were also assessed. Statistical Analysis:
      Descriptive statistics was used to see the feasibility and adherence. The paired
      t-test was used to compare various pre and postintervention outcome measures.
      Results: Fourteen patients (median age: 36 years, range13-65 years) of malignant
      lymphoma were enrolled in the study. Male-to-female ratio was 9:5. Non-Hodgkin's
      lymphoma patients constituted 64%. The recruitment rate was 93%. Favorable
      retention (100%), acceptability (97%), adherence (78.6%), and no serious adverse
      events following yoga practice were reported. Improvement was also found in
      HRQOL, fatigue, sleep, depression, and anxiety. However, it needs further
      validation in a randomized study. Conclusion: Home-based yoga program is safe and
      feasible among the patients suffering from malignant lymphoma receiving
      chemotherapy.

PMID- 30233122
TI  - Effect of a Structured Yoga Program on Fatigue, Depression, Cardiorespiratory
      Fitness, and Quality of Life in a Postmenopausal Breast Cancer Survivor.
AB  - A 52-year-old postmenopausal female diagnosed with duct carcinoma of the left
      breast underwent modified radical mastectomy 2 years ago. She had completed six
      cycles of chemotherapy postsurgery and complained of significant fatigue and
      depression. Her fatigue score on Piper Fatigue Scale was 4.1 and depression score
      on Beck's Depression Inventory was 22. She had a poor 6-min walking distance and
      a reduced quality of life. She was given a structured yoga program for 40 min
      five times a week for 4 weeks. Results showed a marked reduction in fatigue and
      depression scores and improvement in cardiorespiratory fitness. Her quality of
      life also showed improvement after the structured yoga therapy. This case report
      highlights the benefits of yoga for reducing fatigue, depression, and improving
      the cardiorespiratory fitness and overall quality of life in a breast cancer
      survivor.

PMID- 30233123
TI  - The Future of Earth Observation in Hydrology.
AB  - In just the past five years, the field of Earth observation has progressed beyond
      the offerings of conventional space agency based platforms to include a plethora
      of sensing opportunities afforded by CubeSats, Unmanned Aerial Vehicles (UAVs),
      and smartphone technologies that are being embraced by both for-profit companies
      and individual researchers. Over the previous decades, space agency efforts have
      brought forth well-known and immensely useful satellites such as the Landsat
      series and the Gravity Research and Climate Experiment (GRACE) system, with costs
      typically on the order of one billion dollars per satellite and with concept-to
      launch timelines on the order of two decades (for new missions). More recently,
      the proliferation of smartphones has helped to miniaturise sensors and energy
      requirements, facilitating advances in the use of CubeSats that can be launched
      by the dozens, while providing ultra-high (3-5 m) resolution sensing of the Earth
      on a daily basis. Start-up companies that did not exist five years ago now
      operate more satellites in orbit than any space agency, and at costs that are a
      mere fraction of the cost of traditional satellite missions. With these advances
      come new space-borne measurements, such as real-time high-definition video for
      tracking air pollution, storm-cell development, flood propagation, precipitation
      monitoring, or even for constructing digital surfaces using structure-from-motion
      techniques. Closer to the surface, measurements from small unmanned drones and
      tethered balloons have mapped snow depths, floods, and estimated evaporation at
      sub-meter resolutions, pushing back on spatio-temporal constraints and delivering
      new process insights. At ground level, precipitation has been measured using
      signal attenuation between antennae mounted on cell phone towers, while the
      proliferation of mobile devices has enabled citizen-scientists to catalogue
      photos of environmental conditions, estimate daily average temperatures from
      battery state, and sense other hydrologically important variables such as channel
      depths using commercially available wireless devices. Global internet access is
      being pursued via high altitude balloons, solar planes, and hundreds of planned
      satellite launches, providing a means to exploit the Internet of Things as an
      entirely new measurement domain. Such global access will enable real-time
      collection of data from billions of smartphones or from remote research
      platforms. This future will produce petabytes of data that can only be accessed
      via cloud storage and will require new analytical approaches to interpret. The
      extent to which today's hydrologic models can usefully ingest such massive data
      volumes is unclear. Nor is it clear whether this deluge of data will be usefully
      exploited, either because the measurements are superfluous, inconsistent, not
      accurate enough, or simply because we lack the capacity to process and analyse
      them. What is apparent is that the tools and techniques afforded by this array of
      novel and game-changing sensing platforms present our community with a unique
      opportunity to develop new insights that advance fundamental aspects of the
      hydrological sciences. To accomplish this will require more than just an
      application of the technology: in some cases, it will demand a radical rethink on
      how we utilise and exploit these new observing systems to enhance our
      understanding of the Earth and its linked processes.

PMID- 30233124
TI  - Processes of Belonging for Citizen-Children of Undocumented Mexican Immigrants.
AB  - In this article, we focus on the developmental contexts of middle childhood and
      early adolescence to explore the lives of citizen-children living with
      undocumented Mexican parents. We draw on the concept of belonging to highlight
      the distinct situation of citizen-children and the ways in which they come to
      understand their place in a world. To capture the experiences of citizen-children
      born to undocumented Mexican immigrant parents and their sense of belonging to
      place and community, we conducted in-depth interviews with 83 citizen-children in
      late childhood and early adolescence in three groups. One group of citizen
      children lived in Mexico after their parents' deportation. Another group remained
      in the U.S. after parents were detained or deported. The third group did not have
      a parent in deportation proceedings. Qualitative analyses of children's recorded
      interviews revealed their experiences of discovery of parents' undocumented
      status; political, social and material exclusion; and rupture of family ties.
      Children were keenly aware that birthright citizenship afforded them numerous
      privileges unavailable to their parents, but that it did not extend to the very
      privilege, they valued most: an intact family. The loss of parents through
      detention or deportation forced some children to consider existential questions
      about who they were and where they belonged, sometimes pitting family members
      against one another. Our findings suggest that belonging is intimately tied to
      broader forces of legal persecution that go beyond individualized notions of
      illegality and have deep, possibly lasting psychological effects.

PMID- 30233125
TI  - Implementing a Braided Home-based Parent-support Curriculum: Lessons Learned.
AB  - A singular parent-support program is limited in its ability to address multiple
      child and family needs. One innovative solution is braiding, a process in which
      two evidence-based programs are systematically combined as a newly tailored,
      cohesive curriculum. In this paper we describe the systematic braiding of two
      parent-support curricula, Parents as Teachers(r) and SafeCare(r). We highlight
      implementation challenges to inform future planning and braiding efforts. Based
      on qualitative data (n = 13), we discuss five lessons learned, including
      identifying a pedagogical approach and sustainability at the model- and site
      level. Implications and future directions for braiding and implementation are
      also discussed.

PMID- 30233126
TI  - Prevalence of ocular morbidity among children aged 17 years or younger in the
      eastern India.
AB  - Purpose: Childhood ocular morbidity involves a spectrum of eye diseases that
      critically impact the mental development, future education and quality of life.
      However, there is limited evidence about the early detection and appropriate
      treatment of ocular morbidity in children <20 years. This study was aimed to
      assess the prevalence and make a comparison between the different types of ocular
      morbidity in children of both sexes in the age group of 6-17 years in the eastern
      India. Methods: A cross-sectional survey of ocular morbidity among children <17
      years of age who presented at the Department of Ophthalmology, Kalinga Institute
      of Medical Sciences, Bhubaneswar, and Vision Care Center for Retina, Bhubaneswar,
      in the eastern India between January 2015 and March 2018 was accomplished.
      Demographic information, visual acuity, type of eye injury, refractive errors and
      other detailed ophthalmic examination were screened. Results: A total of 633
      children (age 6-17 years) were examined in this study. The majority of cases were
      observed in children of age 12-17 years, accounting for almost close to half of
      all the cases. The prevalence of ocular morbidity was 45.92% in males and 53.97%
      in females. The most common ocular morbidity in children encountered was
      refractive error (54.62%), followed by congenital abnormalities (9%), allergic
      conjunctivitis (8.52%) and traumatic eye injury (7.1%). There was an increase in
      ocular morbidity with age, especially the refractive error and congenital
      abnormalities. Conclusion: A large number of ocular morbidity was observed in
      children of age <17 years. Since most of this morbidity was preventable or
      treatable, reasonable service for ocular morbidity and early age screening are
      effective methods to reduce this load. Moreover, health education for the
      prevention of childhood ocular morbidity and, at the same time, early
      presentation of children to ophthalmic hospitals for the treatment of eye
      disorders are essential.

PMID- 30233128
TI  - Small-aperture intraocular lens tolerance to induced astigmatism.
AB  - Purpose: This prospective, single-site study aimed to assess the corresponding
      change in monocular visual acuity with induced astigmatic defocus in subjects
      implanted with a small-aperture intraocular lens (IOL). Patients and methods: Ten
      subjects with a mean age of 65.1 years were recruited. Eleven eyes of these 10
      subjects were implanted (9 unilaterally, 1 bilaterally) with an IC-8 small
      aperture IOL. Baseline manifest refraction and best-corrected distance visual
      acuity were measured with a Snellen chart (Tumbling E chart). Astigmatic defocus
      was induced in the same axis as the manifest sphere-cylinder refraction or at 180
      degrees  for a spherical refraction. Cylinder defocus was reduced in 0.50 D steps
      from -2.50 D, and distance visual acuity was measured at each level of defocus.
      Results: Mean distance visual acuity was 0.08 logarithm of minimum angle of
      resolution (logMAR) +/-0.08 (20/24) at 1.50 D of defocus, 0.18 logMAR +/-0.08
      (20/30) at 2.00 D of defocus, and 0.24 logMAR +/-0.07 (20/35) at 2.50 D of
      defocus. Eight out of 10 subjects achieved 20/25 or better vision with 1.50 D of
      cylinder defocus, and all subjects were 20/30 or better. Ten out of 11 subjects
      were 20/40 or better with 2.50 D of defocus. Conclusion: The IC-8 IOL shows good
      tolerance to astigmatic defocus with minimal effect on visual acuity. Overall,
      20/25 or better distance acuity was maintained through 1.50 D cylinder defocus.

PMID- 30233127
TI  - Corneal imaging and densitometry measurements in keratoconus patients to monitor
      disease progression and treatment outcomes after contact lens or Intacs
      treatment.
AB  - Aim: The aim of this study was to compare the pre- and posttreatment corneal
      densitometry and corneal thickness value of keratoconus (KCN) patients managed
      via contact lenses (CLs) or by both intrastromal corneal rings and contact
      lenses. Patients and methods: This prospective study was performed at the
      Manchester Royal Eye Hospital, UK. Patients were recruited before treatment and
      followed up for 12 months. Data of corneal densitometry and corneal thickness
      were collected using the Oculus Pentacam at the pretreatment visit and
      posttreatment visit at 12 months. Results: Corneal clarity significantly differs
      between both groups at pre treatment at zone 0-2 mm for the anterior layer
      (P=0.002). The same diversity is present at zone 2-6 mm for the anterior layer
      (P=0.003) and posterior layer (P=0.008). The corneal clarity diversity found was
      not statistically significant at 12 months post treatment (P>0.05). Corneal
      thickness was found to be statistically significantly different between pre
      treatment and post treatment for the CL group for central corneal thickness (CCT)
      and thinnest area (P=0.01 and P=0.02), respectively. Discussion: This study shows
      that KCN management with Intacs was found to be effective in maintaining corneal
      clarity for a longer time than that with CL alone. On the other hand, corneal
      clarity reduces with disease progression in cases managed with CLs only. Analysis
      of Oculus Pentacam images provides an objective evaluation to monitor the corneal
      status after these different pathways of management.

PMID- 30233130
TI  - Erratum: Risk factors for requirement of filtration surgery after vitrectomy in
      patients with proliferative diabetic retinopathy [Corrigendum].
AB  - [This corrects the article on p. 733 in vol. 12, PMID: 29713141.].

PMID- 30233129
TI  - Monovision LASIK in emmetropic presbyopic patients.
AB  - Background: To evaluate the efficacy and patient satisfaction of laser in situ
      keratomileusis (LASIK) monovision correction in presbyopic emmetropic patients.
      Methods: A retrospective review of 294 patients who underwent LASIK for
      monovision was conducted. All patients had preoperative uncorrected distance
      visual acuity in each eye of 20/25 or better in both eyes and underwent primary
      LASIK treatment in one eye with a near target; 82 patients underwent surgery in
      the distant eye for hypermetropia. Patients completed a patient-reported-outcome
      questionnaire at their one-month postoperative visit. Analysis was performed on a
      per patient basis with a logistic regression model. Results: Patients achieved a
      postoperative mean spherical equivalent of -0.05 diopters (D) in the distant eye
      and -1.92 D in the near eye. Prior to surgery, 64.7% (n=178) of patients reported
      they were satisfied or very satisfied with their vision; postoperatively, this
      increased to 85.4% (n=251). The greatest predictor of dissatisfaction after
      surgery was severe patient-reported visual phenomena (glare, halos, starbursts,
      ghosting) (odds ratio 1.18, P=0.001). Conclusions: LASIK monovision for
      presbyopic patients with low refractive error and good preoperative uncorrected
      distance visual acuity is both safe and effective with high patient satisfaction.
      Patients who were dissatisfied in the postoperative period tended to be those
      with postoperative visual symptoms.

PMID- 30233131
TI  - Factors influencing the filtration-bleb volume after Ex-PRESS(r) surgery.
AB  - Purpose: The aim of this study was to investigate the factors influencing the
      volume of the filtration bleb after Ex-PRESS(r) surgery. Methods: This was a
      retrospective non-randomized study. After excluding patients who had undergone an
      additional glaucoma surgery, 99 glaucoma patients who underwent Ex-PRESS(r)
      surgeries and were followed up for >2 years were analyzed. We used anterior
      segment optical coherence tomography to measure the bleb volume, and compared the
      volume at 1 year with that at 2 years after surgery. We also examined potential
      influencing factors, including age, number of medications, central corneal
      thickness, type of glaucoma, preoperative intraocular pressure (IOP),
      postoperative IOP, reduction ratio of IOP, history of trabeculotomy, and
      operation method (Ex-PRESS(r) surgery only or simultaneous cataract surgery).
      Results: Ex-PRESS(r) surgeries significantly decreased the IOP from 26.3+/-9.7
      mmHg to 11.6+/-3.7 mmHg after 24 months (P<0.001). The success rate at 2 years
      was 81.2% (IOP >=21 mmHg or >=20% reduction from the baseline IOP). The results
      showed that age, postoperative IOP, glaucoma type, and simultaneous cataract
      surgeries influenced the filtration-bleb volume. Conclusion: Advanced age, higher
      postoperative IOP, pseudo-exfoliation glaucoma, and simultaneous cataract
      surgeries were all found to decrease the volume of the filtration bleb.

PMID- 30233132
TI  - Small incision lenticule extraction (SMILE) techniques: patient selection and
      perspectives.
AB  - Refractive lenticule extraction is becoming the procedure of choice for the
      management of myopia and myopic astigmatism owing to its precision, biomechanical
      stability, and better ocular surface. It has similar safety, efficacy, and
      predictability as femtosecond laser-assisted in situ keratomileusis (FS-LASIK)
      and is associated with better patient satisfaction. The conventional technique of
      small incision lenticule extraction (SMILE) involves docking, femtosecond laser
      application, lenticule dissection from the surrounding stroma, and extraction. It
      has a steep learning curve compared to conventional flap-based corneal ablative
      procedures, and the surgical technique may be challenging especially for a novice
      surgeon. As SMILE is gaining worldwide acceptance among refractive surgeons,
      different modifications of the surgical technique have been described to ease the
      process of lenticule extraction and minimize complications. Good patient
      selection is essential to ensure optimal patient satisfaction, and novice
      surgeons should avoid cases with low myopia (thin refractive lenticules),
      difficult orbital anatomy, high astigmatism, or uncooperative, anxious patients
      to minimize complications. A comprehensive MEDLINE search was performed using
      "small incision lenticule extraction," "SMILE," and "refractive lenticule
      extraction" as keywords, and we herein review the patient selection for SMILE and
      various surgical techniques of SMILE with their pros and cons. With increasing
      surgeon experience, a standard technique is expected to evolve that may be
      performed in all types of cases with optimal outcomes and minimal adverse
      effects.

PMID- 30233133
TI  - Posterior capsular complication rates with femtosecond laser-assisted cataract
      surgery: a consecutive comparative cohort and literature review.
AB  - Purpose: The aim of the study was to determine whether femtosecond-assisted laser
      cataract surgery (FLACS) reduces the posterior capsular complication (PCC) rate
      compared to manual cataract surgery when performed by an experienced surgeon.
      Patients and methods: We reviewed 2,021 consecutive FLACS procedures between 1
      June 2012 and 30 August 2017. All cases of posterior capsular rupture (PCR) with
      or without vitreous prolapse or zonular dialysis (ZD) that prevented an in-the
      bag placement of the intraocular lens were included. Risk factors were noted and
      outcomes documented. Results: Six eyes of 2,021 (0.3%) who underwent FLACS had
      either a PCR or ZD. One eye (0.25%) of 403 eyes that had manual cataract surgery
      had a PCR. There was no significant difference in outcomes. Risk factors included
      advanced age, dense nuclei, pseudoexfoliation and small pupil. Only a single case
      in the FLACS series may have been directly attributed to the FLACS procedure.
      Conclusion: This study provides evidence that there is no significant difference
      in the PCC rate between FLACS and manual cataract surgery in the hand of an
      experienced surgeon who performs >350 cases annually. This low rate of
      complications may be achieved by less experienced surgeons adopting FLACS.

PMID- 30233134
TI  - Herpesviridae prevalence in aqueous humor using PCR.
AB  - Objective: The aim of this study was to determine the prevalence of Herpesviridae
      family in aqueous humor and the prevalence of antibodies against Herpesviridae
      family in serum. Methods: Participants undergoing cataract surgery were included
      in the study. Serum for viral serology including herpes simplex virus (HSV),
      varicella zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV)
      was collected. Aqueous humor specimen was tapped for PCR analysis. Results:
      Ninety-two participants were included with a mean age of 67.67 years (SD +/
      12.51). The prevalence of positive serology tests was 83.3% for HSV, 94.0% for
      VZV, 98.8% for EBV, and 97.6% for CMV. A total of 66 aqueous humor specimens were
      negative for PCR of Herpesviridae family. Conclusion: This study showed previous
      HSV, VZV, EBV and CMV infections in >90% of the Thai population, while no viral
      presence was detected in aqueous humor. Thus, the serology test is unrelated to
      the presence of virus in the eye. We suggest that PCR is a valuable tool to
      diagnose intraocular viral infection and detect virus presenting active
      infection.

PMID- 30233135
TI  - Visual evoked potential repeatability using the Diopsys NOVA LX fixed protocol in
      normal older adults.
AB  - Purpose: The purpose of this study was to evaluate the intrasession and
      intersession repeatability of visual evoked potentials in normal adults over 40
      years of age as recorded using the Diopsys NOVA LX fixed protocol. Methods:
      Inclusion criteria were adults aged over 40 years with best corrected distance
      acuity of 20/40 or better in each eye. Subjects underwent three consecutive
      visual evoked potential examinations using the Diopsys NOVA LX fixed protocol.
      All examination procedures were carried out in accordance with the manufacturer
      recommendations. To assess intersession repeatability, nine subjects returned in
      2-6 weeks for repeat examination. Results: A total of 46 subjects were recruited.
      Mean +/- SD age: 53+/-9 years (range: 40-84 years); 69% of subjects were female
      and 80% were non-white. Coefficients of variation (CVs) and intra-class
      correlation coefficients (ICCs) revealed greater repeatability for P100 latency
      (CV: 3%-7%; ICC: 0.39-0.76) than for P100 amplitude (CV: 21%-33%; ICC: 0.34-0.69)
      and greater repeatability for recordings made with high contrast stimuli
      (amplitude CV: 21%-23%; latency CV: 3%-7%) than low contrast stimuli (amplitude
      CV: 24%-33%; latency CV: 6%-7%). Minimum detectable change values ranged between
      4.50 and 9.95 uv for amplitude and 8.16-15.26 ms for latency. Repeatability was
      not influenced by age, sex, or race. Conclusion: The Diopsys NOVA LX fixed
      protocol demonstrated clinically acceptable intrasession and intersession
      repeatability in these healthy older adults, with latency being more repeatable
      than amplitude and examinations employing high contrast stimuli being more
      repeatable than those using low contrast stimuli.

PMID- 30233136
TI  - 17beta-estradiol ameliorates oxidative stress and blue light-emitting diode
      induced retinal degeneration by decreasing apoptosis and enhancing autophagy.
AB  - Purpose: This study aimed to assess the effects of 17beta-estradiol (betaE2) on
      blue light-emitting diode (LED)-induced retinal degeneration (RD) in rats and
      hydrogen peroxide (H2O2)-induced retinal pigment epithelium cell injury in humans
      and elucidate the protective mechanism of betaE2 underlying these processes.
      Methods: Female ovariectomized (OVX) rats were intravitreally injected with
      betaE2 before blue LED exposure (3,000 lux, 2 hours). Retinal function and
      morphology were assayed via electroretinogram (ERG) and H&E, respectively. Cell
      viability was assayed using the Cell Counting Kit-8. Cell ROS were measured using
      dichlorofluorescein fluorescence. Apoptosis was evaluated by TUNEL and Annexin
      V/propidium iodide staining. Gene expression and protein expression were
      quantified using quantitative real-time RT-PCR, Western blotting, and
      immunohistochemistry. Autophagosomes were examined by electron microscopy.
      Results: Female OVX rats were exposed to blue LED, inducing RD. betaE2
      significantly prevented the reduction in the a- and b-wave ERG amplitudes and the
      disruption of retinal structure, the loss of photoreceptor cells, and the
      decrease in the thickness of the outer nuclear layer caused by blue LED exposure.
      betaE2 also decreased cell apoptosis in the retina in blue LED-induced RD.
      Additionally, betaE2 reduced ROS levels and apoptosis in H2O2-treated human
      retinal pigment epithelial (ARPE-19) cells. Furthermore, betaE2 increased the
      protein expression of p-Akt and Bcl-2 and decreased the protein expression of
      cleaved caspase-3 and Bax during blue LED-induced retinal damage and in H2O2
      treated ARPE-19 cells. betaE2 also increased the number of autopha-gosomes and
      upregulated the expression of LC3-II/LC3-I and Beclin 1 in these processes.
      Conclusion: betaE2 protects against blue LED-induced RD and H2O2-induced
      oxidative stress by acting as an antioxidant, and its protective mechanism might
      occur by reducing apoptosis and enhancing autophagy; betaE2 may be a novel and
      effective therapy for age-related macular degeneration.

PMID- 30233137
TI  - Dingchuan tang essential oil inhibits the production of inflammatory mediators
      via suppressing the IRAK/NF-kappaB, IRAK/AP-1, and TBK1/IRF3 pathways in
      lipopolysaccharide-stimulated RAW264.7 cells.
AB  - Background: Dingchuan tang (asthma-relieving decoction), a formula of nine herbs,
      has been used for treating respiratory inflammatory diseases for >400 years in
      the People's Republic of China. However, the mechanisms underlying the anti
      inflammatory action of dingchuan tang is not fully understood. This study aims to
      investigate the effects of Dingchuan tang essential oil (DCEO) on inflammatory
      mediators and the underlying mechanism of action. Materials and methods: DCEO was
      extracted by steam distillation. Lipopolysaccharide (LPS)-stimulated RAW264.7
      macrophages were used as the cell model. Production of nitric oxide (NO) was
      determined by the Griess test. Protein secretion and mRNA levels of inflammatory
      mediators were measured by the enzyme-linked immunosorbent assay (ELISA) and
      quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Protein
      levels were examined by Western blot. Nuclear localization of nuclear factor
      kappa B (NF-kappaB) was detected using immunofluorescence analyses. Results: DCEO
      significantly reduced LPS-triggered production of NO and prostaglandin E2 (PGE2)
      and decreased protein and mRNA levels of inducible nitric oxide synthase (iNOS)
      and cyclooxygenase-2 (COX-2). LPS induced upregulation of protein and mRNA levels
      of cytokines (interleukin-1beta [IL-1beta], interleukin-6 [IL-6], tumor necrosis
      factor-alpha [TNF-alpha]), and chemokines (monocyte chemoattractant protein-1
      [MCP-1], chemokine [C-C motif] ligand 5 [CCL-5], and macrophage inflammatory
      protein [MIP]-1alpha) were suppressed by DCEO treatment. Phosphorylation and
      nuclear protein levels of transcription factors (activator protein-1 [AP-1], NF
      kappaB, interferon regulatory factor 3 [IRF3]) were decreased by DCEO. Protein
      levels of phosphorylated IkappaB-alpha, IkappaB kinase alpha/beta
      (IKKalpha/beta), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt),
      TGF beta-activated kinase 1 (TAK1), TANK-binding kinase 1 (TBK1), extracellular
      signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), and c
      Jun N-terminal kinase (JNK) were lowered by DCEO. Moreover, degradation of
      interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4 induced by LPS was
      inhibited by DCEO treatment. Conclusion: Suppression of the interleukin-1
      receptor-associated kinase (IRAK)/NF-kappaB, IRAK/AP-1 and TBK1/IRF3 pathways was
      associated with the inhibitory effects of DCEO on inflammatory mediators in LPS
      stimulated RAW264.7 macrophages. This study provides a pharmacological
      justification for the use of dingchuan tang in managing inflammatory disorders.

PMID- 30233138
TI  - Safety and efficacy of elbasvir/grazoprevir for the treatment of chronic
      hepatitis C: current evidence.
AB  - Treatments for hepatitis C virus (HCV) have advanced greatly, becoming more
      efficacious with fewer adverse events, due to the availability of direct-acting
      antiviral agents, which target specific steps in the HCV life cycle. Recently, a
      combination regimen consisting of the HCV nonstructural protein 5A inhibitor
      elbasvir (EBR) and the HCV NS3/4A protease inhibitor grazoprevir (GZR) was
      approved for the treatment of patients with chronic HCV and genotypes (Gts) 1 and
      4 in various countries. In Phase III trials, the combination of EBR/GZR (fixed
      dose combination table or single agent) for 12 or 16 weeks of treatment with or
      without ribavirin resulted in a high sustained virological response at 12 weeks
      in treatment-naive and treatment-experienced patients with HCV Gt 1a, 1b, 4, or
      6, including special populations, such as individuals with advanced chronic
      kidney disease, HCV-HIV coinfection, and compensated cirrhosis. In this review,
      we focus on the mode of action, pharmacokinetics, clinical applications,
      efficacy, and safety profile of EBR/GZR, including special populations who have
      been considered refractory from the extensive evidence of clinical trials.

PMID- 30233139
TI  - Are laboratory parameter (biomarker) values similar to the healthy volunteer
      reference range in all patient populations?
AB  - Background: Liver biomarkers alanine aminotransferase (ALT) and bilirubin in
      patients with hepatitis are above the healthy volunteer reference range (HVRR) at
      baseline (prior to receiving the clinical trial medication). Discussions continue
      as how to best distinguish drug-induced liver injury in patients with abnormal
      baseline values participating in clinical trials. This study investigated if
      other baseline routine clinical safety biomarkers (lab parameters) are different
      from the HVRR. Materials and methods: Clinical trial data (TransCelerate dataset)
      from placebo and standard of care treated patients were compared to the HVRR
      using a 10% threshold above or below the HVRR to classify a lab parameter in a
      patient population as potentially different from the HVRR at baseline. The
      TransCelerate dataset, batch 4, contained data from patients with Alzheimer's,
      asthma, COPD, cardiovascular disease, diabetes, hidradenitis,
      hypercholesterolemia, rheumatoid arthritis, schizophrenia, stroke, and ulcerative
      colitis. A subset of the 200 biomarkers in Trans-Celerate were evaluated in this
      pilot: glucose, platelet count, neutrophil count, ALT, aspartate aminotransferase
      (AST), and bilirubin. Results: Glucose was potentially higher than the HVRR in
      patients with diabetes, COPD, cardiovascular disease, hypercholesterolemia, and
      schizophrenia. At least one or more of the hematology and hepatic biomarkers were
      different from the HVRR in at least one patient population, except bilirubin. All
      the patient populations, except Alzheimer's and asthma, had at least one
      biomarker that was higher than the HVRR. Summary: The routine biomarkers
      evaluated in this pilot study demonstrated that not all lab parameters in patient
      populations are similar to the HVRR. Further efforts are needed to determine
      which biomarkers are different from the HVRR and how to evaluate the biomarkers
      in patient populations for detecting drug-induced altered lab values in clinical
      trials.

PMID- 30233140
TI  - Efficacy and safety of a fixed-dose combination of nimesulide/pantoprazole
      compared to naproxen/esomeprazole for pain relief in patients with osteoarticular
      diseases and dyspeptic symptoms.
AB  - Purpose: This study investigated the safety and efficacy of fixed-dose
      combination tablets of naproxen/esomeprazole magnesium and
      nimesulide/pantoprazole to determine if both regimens are equally suited to
      relieve pain in patients with osteoarticular diseases and dyspeptic symptoms.
      Methods: Patients were randomly assigned to receive either
      nimesulide/pantoprazole (100 mg/20 mg) twice daily or naproxen/esomeprazole
      magnesium (500 mg/20 mg) twice daily for 14 days. The primary endpoint was
      defined as the mean change in modified Western Ontario and McMaster Universities
      Osteoarthritis Index pain subscale. Secondary endpoints were mean visual analog
      scale score of dyspeptic symptoms (nausea, abdominal discomfort/pain, epigastric
      burning, postprandial fullness), mean visual analog scale score of individual
      dyspeptic symptoms, and individual score of dyspeptic symptoms according to
      patient diary. This study is registered at ClinicalTrials.gov: NCT01670552.
      Results: A total of 490 patients were enrolled and randomized, and 399 completed
      treatment (naproxen/esomeprazole, n=201; nimesulide/pantoprazole, n=198). The
      difference in mean change in the modified Western Ontario and McMaster
      Universities Osteoarthritis Index pain score after 7 days of treatment between
      the two treatment groups was 2.33 mm (95% CI, -1.22 to 5.89 mm). After 14 days of
      therapy, the difference was 0.45 mm (95% CI, -3.29 to 4.19 mm). The most common
      adverse events in the pooled group were abdominal discomfort, abdominal
      distention, dyspepsia, and nausea, but none of these was deemed to be clinically
      meaningful. Conclusion: The present study demonstrated noninferiority of a 14-day
      regimen with a fixed-dose combination of nimesulide/pantoprazole compared to
      naproxen/esomeprazole for the treatment of osteoarticular pain.

PMID- 30233142
TI  - The effect of food and liquid pH on the integrity of enteric-coated beads from
      cysteamine bitartrate delayed-release capsules.
AB  - Background: Cysteamine bitartrate delayed-release (DR) capsule (Procysbi(r)) is
      approved for treatment of nephropathic cystinosis in the USA, Canada, and the EU.
      The capsules contain cysteamine bitartrate beads that are enteric coated with
      acid-resistant Eudragit L 30 D-55, preventing drug release in the acidic stomach
      environment while allowing dissolution of the beads in the more alkaline
      environment of the small intestine. Patients who have difficulty swallowing
      capsules can open capsules, sprinkle beads onto 4 ounces of a suitable food or
      liquid, gently mix, and consume the entire content within 30 minutes. Foods found
      to be suitable for administration, and described in the Procysbi US labeling,
      include fruit juices (except grapefruit juice), applesauce, and berry jelly;
      there are minor variations in the foods and liquids recommended by regulatory
      authorities in other countries. This study aimed to assess the stability of
      enteric-coated beads exposed to additional foods at different conditions to
      expand the list of suitable foods for drug administration. Methods: For each test
      condition, beads from eight opened 75 mg cysteamine bitartrate DR capsules were
      gently mixed with test food and maintained at a prespecified temperature and
      duration; remaining undissolved beads were then recovered from the food. The
      recovered beads were split into two portions: one assayed for remaining drug
      content and the other subjected to dissolution testing to assess the effect on
      the drug-release profile. Results: The results show that bead integrity was
      maintained when mixed with foods at pH values <5.5 at all time points when
      refrigerated (2 degrees C-8 degrees C) and at room (20 degrees C-22 degrees C)
      and lukewarm (37 degrees C-41 degrees C) temperatures. Bead integrity was not
      maintained when mixed with foods at pH values of >=5.5 at room temperature.
      Conclusion: The results from this in vitro dissolution study help in identifying
      additional foods that may be used for the administration of cysteamine bitartrate
      DR beads from opened capsules using the sprinkle method.

PMID- 30233141
TI  - Astragaloside IV/lncRNA-TUG1/TRAF5 signaling pathway participates in podocyte
      apoptosis of diabetic nephropathy rats.
AB  - Objective: This study aims to figure out the mechanism of astragaloside IV (AS
      IV) in the protection of podocyte apoptosis in diabetic nephropathy (DN) rats.
      Materials and methods: Streptozotocin (STZ) was used to induce diabetes in rats,
      and the diabetic rats were treated with 5 mg/kg/d of AS-IV for 12 weeks.
      Albuminuria level, relative TUG1 and TRAF5 levels, and TRAF5 and cleaved-caspase
      3 protein levels were examined by ELISA, quantitative reverse transcription (qRT)
      PCR, and Western blot analyses, respectively. The interaction between TUG1 and
      TRAF5 was confirmed by RNA pull-down and RNA precipitation. TUNEL assay was used
      to detect podocyte apoptosis. Results: Compared with control rats, DN rats had
      higher albuminuria and TRAF5 levels and lower TUG1 level. AS-IV treatment
      attenuated albuminuria and TRAF5 levels and improved TUG1 level in DN rats. TUG1
      was downregulated and TRAF5 was upregulated in high-glucose-treated MPC5 cells,
      and AS-IV ameliorated the TUG1 level. In addition, TUG1 interacted with TRAF5,
      and TUG1 overexpression promoted degradation of TRAF5 protein. Besides, AS-IV
      modulated TRAF5 expression through regulating TUG1. AS-IV decreased podocyte
      apoptosis via the TUG1/TRAF5 pathway. Finally, in vivo experiment proved that si
      TUG1 abrogated the protective effect of AS-IV on DN. Conclusion: AS-IV attenuated
      podocyte apoptosis and protected diabetic rats from DN via the lncRNA-TUG1/TRAF5
      pathway.

PMID- 30233143
TI  - Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through
      PAK1 inhibition and reduce in vivo tumor growth.
AB  - Purpose: The Epstein-Barr virus (EBV)-associated cancer nasopharyngeal carcinoma
      (NPC) is rare in Europe and North America but is a real public health problem in
      some regions of the world, such as southern Asia, North Africa, and for Inuit
      populations. Due to the anatomy and location of the nasopharynx, surgery is
      rarely used to treat primary NPC cancers. Treatment by radiotherapy, combined or
      not with chemotherapy, are efficient for primary tumors but often do not protect
      against fatal relapses or metastases. Methods: Search for new therapeutic
      molecules through high content screening lead to the identification of Ivermectin
      (IVM) as a promising drug. IVM is a US Food and Drug Administration-approved
      macrocyclic lactone widely used as anthelmintic and insecticidal agent that has
      also shown protective effects against cancers. Results: We show here that IVM has
      cytotoxic activity in vitro against NPC cells, in which it reduces MAPKs pathway
      activation through the inhibition PAK-1 activity. Moreover, all macrocyclic
      lactones tested and a PAK1 inhibitor are cytotoxic in vitro for EBV-positive and
      EBV-negative NPC tumor cells. We have also shown that IVM intraperitoneal
      repeated injections, at US Food and Drug Administration-approved doses, have no
      significant toxicity and decrease NPC subcutaneous tumors development in nude
      mice. Conclusion: Macrocyclic lactones appear as promising molecules against NPC
      targeting PAK-1 with no detectable adverse effect.

PMID- 30233144
TI  - Preliminary study on conjugation of formononetin with multiwalled carbon
      nanotubes for inducing apoptosis via ROS production in HeLa cells.
AB  - Background: The present work was conducted to prepare and evaluate multiwalled
      carbon nanotube-formononetin (MWCNT-FMN) composite for sustained delivery and
      inducing apop-tosis via reactive oxygen species (ROS) production in HeLa cells.
      Methods: The composite was prepared by solution mixing with short carboxylic
      group-functionalized multiwalled carbon nanotubes (MWCNT-COOH). Then the
      composite was characterized by laser particle size analysis, Fourier transform
      infrared spectrometry, X-ray diffractometry, differential scanning calorimetry,
      and scanning electron microscopy. Drug release rates in vitro were determined by
      dialysis method. The in vitro cytotoxicity study was performed using water
      soluble tetrazolium assay. The cellular apoptosis assay, ROS, and mitochondrial
      membrane potential (MMP) of HeLa cells were investigated by acridine orange and
      ethidium bromide double dye, 2',7'-dichlorodihydrofluorescein diacetate, and
      5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide probe,
      respectively. Results: The entrapment efficiency was 28.77%+/-0.15%, and the
      loading capacity was 12.05%+/-0.20%. The release of MWCNT-FMN was sustained, and
      the cumulative release rate of formononetin (FMN) from MWCNT-COOH was higher at
      pH 7.4 than at pH 5.3. The in vitro cytotoxicity assay demonstrated that FMN,
      MWCNT-COOH, and MWCNT-FMN had no significant effects on the proliferation and
      viability of mouse fibroblast 3T3 cells over 48 hours, while the cell growth
      inhibition of the three samples showed concentration-dependent for HeLa cells.
      Biological assay suggested FMN and MWCNT-FMN could induce apoptosis in HeLa
      cells, meanwhile the cells exhibited stronger ROS signal and more depolarized MMP
      than that of the control group. Conclusion: These results preliminarily
      demonstrated that MWCNT-FMN exerted anticancer efficacy through cellular
      apoptosis induced by ROS-mediated mitochondrial dysfunctions in HeLa cells.

PMID- 30233145
TI  - Alpha lipoic acid combined with epalrestat: a therapeutic option for patients
      with diabetic peripheral neuropathy.
AB  - Background: Alpha lipoic acid (ALA), a type of antioxidant, is used in
      combination with epalrestat in the treatment of diabetic peripheral neuropathy
      (DPN). However, whether combined treatment is superior to epalrestat monotherapy
      is controversial. Methods: We conducted a systematic search of PubMed, Cochrane
      Library and Chinese databases to identify all randomized controlled trials (RCTs)
      up to October 31, 2017. Data were extracted to evaluate methodological quality
      and analyzed using Review Manager 5.3.0 software. Results: Twelve studies were
      included. Compared to epalrestat monotherapy, ALA 600 mg/d once a day (qd)
      combined with epalrestat 50 mg three times a day (tid) augmented the total
      effectiveness rate (14 days - risk ratio [RR]: 1.40, 95% CI: 1.16-1.69, P=0.0005;
      28 days - RR: 1.48, 95% CI: 1.27-1.72, P<0.00001); at the same, it could improve
      the median motor nerve conduction velocity (MNCV) and sensory nerve conduction
      velocity (SNCV), peroneal MNCV, and SNCV after 14, 21, and 28 days of treatment
      and could reduce the Toronto Clinical Scoring System (TCSS) (weighted mean
      difference [WMD]: -1.60, 95% CI: (-2.91, -0.29), P=0.02) and Total Symptom Score
      (TSS) (WMD: -0.93, 95% CI: -1.27, -0.60, P<0.00001) after 21 days of treatment.
      The treatment strategy of ALA 300 mg/d qd combined with epalrestat 50 mg tid had
      the same effects in regard to the total effectiveness rate (RR: 1.37, 95% CI:
      1.18-1.59, P<0.0001), median MNCV (WMD: 6.12, 95% CI: 5.04, 7.20, P=0.00001),
      median SNCV (WMD: 6.70, 95% CI: 5.75, 7.65, P=0.00001), peroneal MNCV (WMD: 6.68,
      95% CI: 5.82, 7.55, P=0.00001), and peroneal SNCV (WMD: 4.27, 95% CI: 3.34, 5.20,
      P=0.00001) after 28 days of treatment. Conclusion: ALA combined with epalrestat
      is an effective option for DPN patients. Future large-sample RCTs should be
      conducted to further confirm this finding.

PMID- 30233146
TI  - Anti-HER2 functionalized graphene oxide as survivin-siRNA delivery carrier
      inhibits breast carcinoma growth in vitro and in vivo.
AB  - Background: The success of gene therapy is mostly dependent on the development of
      gene carrier. Graphene oxide (GO) possesses excellent aqueous solubility and
      biocompatibility, which is important for its biochemical and medical
      applications. Our previous work proved that GO can deliver siRNA into cells
      efficiently and downregulate the expression of desired protein. Methods: In this
      study, a novel delivery carrier, GO-R8/anti-HER2 (GRH), was developed by
      conjugating octaarginine (R8) and anti-HER2 antibody with GO as a tumor active
      targeting vector for survivin-siRNA delivery. Results: GRH/survivin-siRNA formed
      nanoglobes of 195+/-10 nm in diameter. Real-time polymerase chain reaction
      analysis revealed that survivin messenger RNA expression showed a 42.4%+/-2.69%
      knockdown. The expression of survivin protein was downregulated to 50.86%+/-2.94%
      in enzyme-linked immunosorbent assay. In MTT tests, GRH exhibited no testable
      cytotoxicity. In vivo, GRH/survivin-siRNA showed gene silencing and inhibition of
      tumor growth. Conclusion: The in vitro and in vivo results consistently
      demonstrated that GRH/survivin-siRNA has potential to be an efficient gene
      silencing carrier for siRNA delivery in cancer therapy.

PMID- 30233147
TI  - Development and validation of an instrument to measure patient engagement in Hong
      Kong Special Administrative Region, China.
AB  - Objective: The objective of this study was to develop, pilot test, and
      psychometrically validate a patient engagement questionnaire, called Patient
      Engagement Index (PEI), in Hong Kong, China. Method: The method employed was
      based on a patient engagement framework and literature review and expert panel
      discussion. A new measure named PEI with 20 items divided into five factors was
      developed. A pilot study of 40 patients was used to confirm the clarity of PEI.
      Explored factor analysis was used to confirm the construct validity. Cronbach's
      alpha, intercorrelation coefficients (ICCs), and weighted kappa were used to
      assess the internal consistency reliability and test-retest reliability
      separately. Rasch model and differential item functioning were also used to
      further confirm the fit of the instrument. Results: In all, 324 participants
      successfully completed the survey. Based on the evaluation of exploratory factor
      analysis and theoretically considerations, a four-factor structure comprising 20
      items was identified. Rasch analysis also confirmed that the model has a good fit
      (ranging from 0.662 to 1.294). All domains were considered internally consistent
      (alpha >0.7). Test-retest showed both ICC (>0.6) and weighted kappa (>0.4)
      meeting the minimum recommended standard. No ceiling or floor effect was found.
      Furthermore, Spearman's correlation coefficient confirmed that PEI had good
      internal validity. Conclusion: PEI was shown to have good reliability and
      validity. This is a short, quick, and appropriate tool to assess the extent of
      patient engagement in both clinical and research settings.

PMID- 30233148
TI  - The association of diabetes-related self-care activities with perceived stress,
      anxiety, and fatigue: a cross-sectional study.
AB  - Purpose: Many people with type 2 diabetes (T2DM) do not sustain sufficient
      diabetes-related self-care activities (DRSCA) in their daily lives. To provide
      additional information about the positive influence of DRSCA, this study was
      conducted to examine whether DRSCA were associated with reduced perceived stress,
      anxiety, and fatigue among people with T2DM and to explore the level of DRSCA,
      perceived stress, anxiety, and fatigue and their association with background
      information. Patients and methods: This study was a cross-sectional survey
      including 251 participants aged 18 years and older recruited from two hospitals
      in the eastern part of China. The study utilized self-report questionnaires that
      consisted of background information, DRSCA, perceived stress, anxiety, and
      fatigue. Hierarchical multiple regression analysis was conducted to explore the
      association of DRSCA with perceived stress, anxiety, and fatigue while adjusting
      for background information. Results: The results indicated that the level of self
      care activities, stress, and fatigue was around middle level. The prevalence of
      anxiety was 19%. A high level of DRSCA was likely to reduce perceived stress but
      was not linked to anxiety and fatigue. Women were more susceptible to stress and
      anxiety, and people who had diabetes for >5 years were more likely to have
      anxiety. The background information included diabetes duration, standardized
      diabetes education, and high social support, all of which are factors that may
      influence DRSCA. Conclusion: The findings suggest that improving the level of
      DRSCA might effectively reduce perceived stress. The potential benefits of DRSCA
      can provide both motivational and evaluative data for self-care programs. In
      addition, the findings show that DRSCA were not linked to anxiety and fatigue,
      which implies that their positive influence on anxiety and fatigue may be offset
      by the load of frequent DRSCA. It is suggested that helping patients to make
      tailored plans to integrate DRSCA into their daily lives is needed. Meanwhile, in
      the background information, it is suggested that standardized diabetes education
      and high social support can benefit DRSCA; in improving psychological health,
      more attention should be paid to women and patients with diabetes duration <5
      years.

PMID- 30233149
TI  - Medication adherence in chronic illness: do beliefs about medications play a
      role?
AB  - Background: Several medicines are prescribed for chronic disease management;
      however, adherence to long-term therapy remains poor. Culture influences beliefs
      about medications and, ultimately, adherence to treatment. There is a paucity of
      data with regard to beliefs about medications in the Middle East region, and it
      remains to be determined how these beliefs would impact treatment adherence.
      Objectives: To investigate the relationship between patients' beliefs about
      medications with self-reported adherence to treatment among a chronically ill
      multicultural patient population. Methods: A prospective cross-sectional study
      was conducted among patients treated for chronic illnesses in the Ministry of
      Health primary care clinics in Kuwait. Patients completed a questionnaire that
      consisted of questions to collect information about their health status and
      demographics using validated instruments: the Beliefs about Medication, Sensitive
      Soma Assessment Scale, and Medication Adherence Report Scale-5 items. The main
      outcome measures were self-reported adherence to medications, beliefs, and
      perceived sensitivity toward medications. Results: Of the 1,150 questionnaires
      distributed, 783 were collected - giving a response rate of 68.1%. Of the 783
      patients, 56.7% were male, 73.7% were married, 53.3% were non-Kuwaitis, and 49.4%
      had low income (<1,000 KD/3,350 USD monthly). Patients self-reported having a
      cardiovascular illness (80.2%), diabetes mellitus (67.7%), respiratory disease
      (24.3%), or mood disorder (28.6%). Participants had a mean of two comorbid
      illnesses and indicated taking an average of four prescription medicines to treat
      them. A structural equation model analysis showed adherence to medications was
      negatively impacted by higher negative beliefs toward medications (beta = -0.46).
      Factors associated with negative beliefs toward medications included marital
      status (being unmarried; beta = -0.14), nationality (being Kuwaiti; beta = 0.15),
      having lower education level (beta = -0.14), and higher illness severity (beta =
      0.15). Younger age (beta = 0.10) and higher illness severity (beta = -0.9) were
      independently associated with lower medication adherence. Income and gender did
      not influence medication adherence or beliefs about medications. The combined
      effect of variables tested in the model explained 24% of the variance in
      medication adherence. Conclusion: Medication adherence is a complex, multifaceted
      issue and patient beliefs about medications contribute significantly, although
      partially, to adherence among a multicultural Middle Eastern patient population.

PMID- 30233150
TI  - Cost-related nonadherence to prescription medications in Canada: a scoping
      review.
AB  - Purpose: The evidence is emerging that prescription medications are the topmost
      drivers of increasing health care costs in Canada. The financial burden of
      medications may lead individuals to adopt various rationing or restrictive
      behaviors, such as cost-related nonadherence (CRNA) to medications. Therefore,
      the purpose of this study is to provide an overview of the type, extent, and
      quantity of research available on CRNA to prescription drugs in Canada, and
      evaluate existing gaps in the literature. Methods: The study was conducted using
      a scoping review methodology. Six databases were searched from inception till
      June 2017. Articles were considered for inclusion if they focused on extent,
      determinants, and consequences of CRNA to prescription medication use in the
      Canadian context. Variables extracted for data charting included author(s), year
      of publication, study design, the focus of the article, sample size, population
      characteristics, and key outcomes or results. Results: This review found 37
      studies that offered evidence on the extent, determinants, and consequences of
      CRNA to prescription medications in Canada. Depending on the population
      characteristics and province, the prevalence of CRNA varies between 4% and 36% in
      Canada. Canadians who are young (between 18 and 64 years), without drug
      insurance, have lower income or precarious or irregular employment, and high out
      of-pocket expenditure on drugs are most likely to face CRNA to their
      prescriptions. The evidence that CRNA has negative health and social outcomes for
      patients is insufficient. Literature regarding the influence of prescribing
      health care professionals on patients' decisions to stop taking medications is
      limited. There is also a dearth of literature that explores patients' decisions
      and strategies to manage their prescription cost burden. Conclusion: More
      evidence is required to make a strong case for national Pharmacare which can
      ensure universal, timely, and burden-free access to prescription medications for
      all Canadians.

PMID- 30233151
TI  - Media representation of vaccine side effects and its impact on utilization of
      vaccination services in Vietnam.
AB  - Background: Media representation of vaccine side effects impacts the success of
      immunization programs globally. Exposure to the media can cause individuals to
      feel hesitant toward, or even refuse, vaccines. This study aimed to explore the
      impact of the media on beliefs and behaviors regarding vaccines and vaccine side
      effects in an urban clinic in Vietnam. Methods: A cross-sectional study was
      conducted in an urban vaccination clinic in Hanoi, Vietnam from November 2015 to
      March 2016. The primary outcomes of this study were the decisions of Vietnamese
      subjects after hearing about adverse effects of immunizations (AEFIs) in the
      media. Socio-demographic characteristics as well as beliefs regarding vaccination
      were also investigated. Multivariate logistic regression was used to identify
      factors associated with subjects' behaviors regarding vaccines. Results: Among
      429 subjects, 68.2% of them said they would be hesitant about receiving vaccines
      after hearing about AEFIs, while 12.4% of subjects said they would refuse
      vaccines altogether after hearing about AEFIs. Wealthy individuals (OR=0.41; 95%
      CI=0.19-0.88), and those who displayed trust in government-distributed vaccines
      (OR=0.20; 95% CI=0.06-0.72) were less likely to display hesitancy regarding
      vaccination. Receiving information from community health workers (OR=0.44; 95%
      CI=0.20-0.99) and their relatives, colleagues, and friends (OR=0.47; 95% CI=0.25
      0.88) was negatively associated with vaccine hesitancy, but facilitated vaccine
      refusal after reading about AEFIs in the media (OR=3.12; 95% CI=1.10-8.90 and
      OR=3.75; 95% CI=1.56-9.02, respectively). Conclusion: Our results reveal a
      significantly high rate of vaccine hesitancy and refusal among subjects living in
      an urban setting in Vietnam, after hearing about AEFIs in the media. Vietnam
      needs to develop accurate information systems in the media about immunizations,
      to foster increased trust between individuals, health care professionals, and the
      Vietnamese government.

PMID- 30233152
TI  - Fatigue of systemic lupus erythematosus in China: contributors and effects on the
      quality of life.
AB  - Objective: Fatigue is a very common symptom of systemic lupus erythematosus
      (SLE), which significantly impairs patients' quality of life. The purpose of this
      study is to evaluate contributors of fatigue and effects of fatigue on the
      quality of life in Chinese SLE patients. Methods: A survey of 119 SLE patients
      using the Fatigue Severity Scale (FSS) to assess the severity of fatigue was
      carried out. SLE patients completed the Systemic Lupus Erythematosus Disease
      Activity Index, the Hospital Anxiety and Depression Scale, the Short Form 36
      health survey and the Pittsburgh Sleep Quality Index. Meanwhile, 105 healthy
      individuals completed FSS, the Hospital Anxiety and Depression Scale and Short
      Form 36 health survey. We used chi-squared analysis, independent samples t-tests
      and logistic regression models to analyze data. Results: Our results found that
      the FSS score of patients with SLE was higher than that of healthy controls. The
      disease duration, anxiety, depression, subjective sleep quality and sleep
      disorders significantly correlated with fatigue in SLE patients. Moreover,
      logistic regression models showed depression and sleep disorders as predictors of
      fatigue. In SLE patients, fatigued patients had lower quality of life than those
      who were non-fatigued. Conclusion: This is the first time to explore contributors
      of fatigue and the influence of fatigue on SLE patients' quality of life in
      China. Our study showed that depression and sleep disorders were predictors of
      fatigue, and fatigue seriously damaged SLE patients' quality of life. The results
      indicate that it is necessary to conduct holistic assessment and effective
      intervention, such as systemic psychiatric screening, psychological care and
      practical sleep guidance, to relieve symptoms of fatigue and finally improve
      their quality of life in SLE patients.

PMID- 30233153
TI  - Understanding ethno-cultural differences in cardiac medication adherence
      behavior: a Canadian study.
AB  - Background: There are ethno-cultural differences in cardiac patients' adherence
      to medications. It is unclear why this occurs. We thus aimed to generate an in
      depth understanding about the decision-making process and potential ethno
      cultural differences, of white, Chinese, and south Asian cardiac patients when
      making the decision to adhere to a medication regimen. Methods: A hierarchical
      descriptive decision-model was generated based on previous qualitative work,
      pilot tested, and revised to be more parsimonious. The final model was examined
      using a novel group of 286 cardiac patients, using their self-reported adherence
      as the reference. Thereafter, each node was examined to identify decision-making
      constructs that might be more applicable to white, Chinese or south Asian groups.
      Results: Non-adherent south Asians were most likely to identify a lack of receipt
      of detailed medication information, and less confidence and trust in the health
      care system and health care professionals. Both Chinese and south Asian
      participants were less likely to be adherent when they had doubts about western
      medicine (eg, the effects and safety of the medication). Being able to afford the
      cost of medications was associated with increased adherence. Being away from home
      reduced the likelihood of adherence in each group. The overall model had 67.1%
      concordance with the participants' initial self-reported adherence, largely due
      to participants' overreporting adherence. Conclusion: These identified elements
      of the decision-making process are generally not considered in traditionally used
      medication adherence questionnaires. Importantly these elements are modifiable
      and ought to be the focus of both interventions and measurement of medication
      adherence.

PMID- 30233154
TI  - The interactive Physical and Cognitive Exercise System (iPACESTM): effects of a 3
      month in-home pilot clinical trial for mild cognitive impairment and caregivers.
AB  - Background: Alzheimer's and related dementias are on the rise, and older adults
      and their families are seeking accessible and effective ways to stave off or
      ameliorate mild cognitive impairment (MCI). Aim: This pilot clinical trial
      (ClinicalTrials.gov Identifier: 03069391) examined neuropsychological and
      neurobiological outcomes of interactive physical and mental exercise.
      Participants and methods: Older adults (MCI and caregivers) were enrolled in a 3
      month, in-home trial of a portable neuro-exergame (the interactive Physical and
      Cognitive Exercise System [iPACESTM]), in which they pedaled and steered along a
      virtual bike path to complete a list of errands (Memory LaneTM).
      Neuropsychological function and salivary biomarkers were measured at pre-, mid-,
      and posttrial. Ten older adults complied with the recommended use of iPACES
      (complete dose; >=2*/wk, 67% of the 15 who also had pre- and postevaluation
      data). Statistical analyses compared change over time and also change among those
      with a complete dose vs inadequate dose. Correlations between change in
      neuropsychological and biomarker measures were also examined. Results: Executive
      function and verbal memory increased after 3 months (p = 0.01; no significant
      change was found with an inadequate dose). Change in salivary biomarkers was
      moderately associated with increasing cognition (cortisol, r = 0.68; IGF-1, r =
      0.37). Conclusion: Further research is needed, but these pilot data provide
      preliminary indications to suggest neuro-exergaming can impact cognitive
      function, perhaps via neurobiological mechanisms, and as such may provide an
      effective and practical way to promote healthy aging.

PMID- 30233155
TI  - A systematic review of tranexamic acid usage in patients undergoing femoral
      fracture surgery.
AB  - Background: Patients undergoing femoral fracture surgery frequently require blood
      transfusion. Tranexamic acid (TXA) has been widely used to decrease transfusion
      rate in joint replacement surgery. Therefore, we conducted a systematic review to
      evaluate the efficacy and safety of TXA usage in femoral fracture surgery.
      Materials and methods: Studies involving TXA usage in femoral fracture surgery
      were searched through four electronic databases. The end points included total
      blood loss, postoperative hemoglobin decline, transfusion rate, thromboembolic
      events, 90-day mortality, and operative time. The present study was performed
      following Cochrane Reviewers' Handbook and Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) statement and was carried out by
      using Stata 14.0 software. Results: Eleven studies concerning intravenous (IV)
      application of TXA and three studies concerning topical administration of TXA
      were included. Twelve studies were randomized controlled trials (RCTs), and one
      was a retrospective cohort study. Regarding IV TXA, our paper indicated that the
      IV TXA group had less total blood loss (weighted mean difference [WMD] = 
      319.282, P = 0.000), lower postoperative hemoglobin decline (WMD = -1.14, P =
      0.000) and lower transfusion rate (risk difference [RD] = -0.172, P = 0.000). No
      significant differences were found in thromboembolic events (RD = 0.008, P =
      0.507), 90-day mortality (RD = 0.009, P = 0.732) and operative time (WMD = 
      2.227, P = 0.103). Regarding topical TXA, no significant differences were found
      in the transfusion rate (RD = -0.098, P = 0.129), postoperative hemoglobin
      decline (WMD = -1.137, P = 0.231), thromboembolic events (RD = -0.017, P = 0.660)
      and operative time (WMD = -4.842, P = 0.136). Conclusion: Our meta-analysis
      demonstrated that both IV and topical application of TXA reduced transfusion rate
      in femoral fracture surgery. However, still further studies are needed to
      identify the optimal route of administration, TXA dosage and timing. In addition,
      high-quality RCTs with a large sample size are required to figure out the safety
      of TXA application, especially in the elderly, before its wide recommendation.

PMID- 30233156
TI  - Physical activity can improve cognition in patients with Alzheimer's disease: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - Background/objective: Alzheimer's disease (AD) is mainly characterized by decline
      of cognitive functions such as memory and learning, which has a high prevalence
      and poor drug efficacy in treatment regimes. A systematic review and meta
      analysis of randomized controlled trials (RCTs) were conducted to evaluate the
      effectiveness of exercise on cognitive function in patients diagnosed with AD.
      Methods: The bibliographic databases (PubMed, Cochrane Library and Embase, and
      Web of Science) and four Chinese databases (Wanfang data, CBM, CNKI, and VIP)
      were searched to identify RCTs published in any language between January 1, 1960,
      and January 1, 2018. Only peer-reviewed articles and RCTs were included. The
      collected data were analyzed by Review Manager (5.3). Results: Overall, 869
      patients diagnosed with AD were included from 13 RCTs. Patients in the
      intervention group received pure exercise interventions and a cognitive test.
      Although there was heterogeneity in intervention methods and cognitive measures
      among studies, meta-analysis (seven studies) supports positive effects of
      physical activity on cognitive function of patients with AD (mean difference [MD]
      =2.53, the 95% CI=0.84 to 4.22, test for overall effect: Z=2.93 [P=0.003]). Eight
      studies demonstrated that exercise improves cognitive function for individuals
      with AD. However, the remaining five studies did not display a beneficial effect
      of exercise on cognitive function in patients with AD. Conclusion: This meta
      analysis and systematic review indicated that exercise intervention might improve
      the cognitive function of AD or slow down the decline of cognition; however, this
      relationship was not always true across studies. RCTs with clear intervention
      criteria, large samples, and long-term follow-up are needed in the future to
      demonstrate the benefits of exercise for cognitive function in AD patients.

PMID- 30233157
TI  - Association between depressive symptoms and sarcopenia in older Chinese community
      dwelling individuals.
AB  - Purpose: The aim of this study was to assess the prevalence of sarcopenia and
      depressive symptoms and estimate the association between them in elderly Chinese
      community-dwelling individuals. Patients and methods: A total of 948 elderly
      Chinese community-dwelling individuals were recruited through leaflets and
      posters from three communities in Chengdu, and 865 participants were analyzed in
      this cross-sectional study. Muscle mass was measured using the bioimpedance
      analysis, handgrip strength was measured with a handheld dynamometer, and
      physical performance was assessed via usual gait speed on a 6 m course.
      Sarcopenia was defined according to the recommended diagnostic algorithm of the
      Asia Working Group for Sarcopenia (AWGS). Depressive symptoms were assessed using
      the Chinese version of 15-item Geriatric Depression Scale (GDS-15) with a score
      of >=5 indicative of the presence of depressive symptoms. Results: A total of 865
      participants were included in the analysis. The participants had a mean age of
      68.68+/-6.46 years. Sixty-one (7.1%) participants and 71 (8.2%) participants were
      identified as having sarcopenia and depressive symptoms, respectively. After
      adjusting for age, sex, and other potential confounders, sarcopenia was found to
      be significantly associated with depressive symptoms (odds ratio [OR]: 2.23, 95%
      CI 1.06-4.92). Conclusion: The prevalence rates of sarcopenia and depressive
      symptoms were 7.1 and 8.2%, respectively, in elderly Chinese community-dwelling
      individuals, and sarcopenia was significantly associated with depressive
      symptoms.

PMID- 30233158
TI  - Cultural stereotypes in care contexts.
AB  - Introduction: The main goal of the present study was to examine the stereotype
      content model (SCM) assumption for universality and to test whether the mediating
      role of cultural views about older adult caregivers is maintained in other health
      care contexts. Methods: One hundred and sixty professionals and volunteers who
      worked with older adults in day care centers (DCCs) and senior citizen centers
      (SCCs) and 1,151 participants from a representative sample of the Spanish
      population were examined using the SCM questionnaire; older adult and personnel
      functioning were assessed through an observation procedure with two subscales of
      the Evaluation Scale from the Sistema de Evaluacion de Residencias de Ancianos.
      Results: The results showed that the context does not seem to influence the
      cultural views about older adults held by caregivers. All results support the
      cultural stereotype pattern in which members of the older adult group are viewed
      with high warmth (HW) and low competence (LC) as posited by the SCM model. With
      respect to the mediation of cultural stereotypes on caregivers/older adult
      functioning, this has not been supported in this study. Neither cultural views of
      warmth (predicted by the SCM) nor views of competence (from our previous studies)
      influence either caregiver functional behaviors or older adult functioning.
      Conclusion: Two post hoc hypotheses can be inferred: 1) there is more variability
      in competence and warmth in DCCs and SCCs and 2) although we did not find
      significant differences in the pattern of competence and warmth in perceived
      cultural stereotypes about older adults, more healthy environments could reduce
      the influence of cognitive views on behavior.

PMID- 30233160
TI  - Erratum: Frailty and nutritional status in older people: the Mini Nutritional
      Assessment as a screening tool for the identification of frail subjects
      [Corrigendum].
AB  - [This corrects the article on p. 1237 in vol. 13, PMID: 30034227.].

PMID- 30233159
TI  - Efficacy and safety of co-administration of resveratrol with meloxicam in
      patients with knee osteoarthritis: a pilot interventional study.
AB  - Background and aim: Resveratrol shows remarkable anti-inflammatory activities in
      experimental models. This study aims to evaluate the effect of resveratrol, as an
      adjuvant with meloxicam (Mlx), on the pain and functional activity during a 90
      day period and monitor the adverse effects on kidney and liver functions, lipid
      profile, and hematological markers. Patients and methods: This study was a double
      blind, placebo-controlled, randomized multi-center study that involved 110
      patients with knee osteoarthritis (OA) and was performed at Sulaimani City, Iraq,
      from December 2016 to September 2017. To assess the effects of Mlx with or
      without resveratrol, pain severity and functional disability were evaluated at
      baseline and after 90 days using the Western Ontario and McMaster Universities
      Osteoarthritis Index. Fasting blood was collected to evaluate the lipid profile
      markers, hematological picture, and liver and kidney functions, in addition to
      vitamin D level. Results: Resveratrol significantly improves pain, functions, and
      associated symptoms compared with placebo. The clinical and biochemical markers
      indicated that 500 mg/day of resveratrol, as an adjuvant with Mlx, is safe and
      well tolerated by the knee OA patients. Conclusion: Resveratrol, as an "add-on"
      medication with Mlx, was superior in terms of safety and efficacy to Mlx alone
      for the treatment of pain and improvement of physical function in patients with
      knee OA.

PMID- 30233162
TI  - Neutrophil to lymphocyte ratio is a better indicator of COPD exacerbation
      severity in neutrophilic endotypes than eosinophilic endotypes.
AB  - Background: Complete blood count parameters provide novel inflammatory markers,
      namely neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio
      (PLR). We aimed to assess any differences in these novel inflammatory markers
      according to exacerbation severity in patients with COPD in both eosinophilic and
      neutrophilic endotypes. Method: This retrospective cross-sectional study was
      conducted at a tertiary education hospital. Previously diagnosed COPD patients
      admitted to the hospital with acute COPD exacerbation (AECOPD) were enrolled into
      the study. Patients were grouped according to COPD endotype, eosinophilic
      (peripheral blood eosinophil rate >=2%) and neutrophilic (peripheral blood
      eosinophil rate <2%), and further subdivided according to place of admission
      (outpatient clinic, ward, or intensive care unit [ICU]) as an indicator of
      disease severity. Complete blood count, biochemistry, C-reactive protein (CRP),
      NLR, PLR, and platelet to mean platelet volume values were recorded from an
      electronic hospital database system and compared among all groups. Results: Of
      the 10,592 patients included in the study, 7,864 were admitted as outpatients,
      2,233 to the wards, and 495 to ICU. Neutrophilic COPD patients (n=6,536, 62%) had
      increased inflammatory markers compared with eosinophilic COPD patients (n=4,056,
      38%); median NLR was 5.11 vs 2.62 (P<0.001), PLR was 175.66 vs 130.00 (P<0.001),
      and CRP was 11.6 vs 7.7 (P<0.001). All values increased relative to admission to
      the outpatient clinic, ward, or ICU: median NLR was 3.20, 6.33, and 5.94,
      respectively, median PLR was 140.43, 208.46, and 207.39, respectively, and median
      CRP was 6.4, 15.0, and 22.8, respectively. The median NLR values of patients in
      outpatients/ward/ICU increased in neutrophilic and eosinophilic endotypes:
      4.21/7.57/8.60 (P<0.001) and 2.50/3.43/3.42 (P=0.81), respectively. CRP showed a
      similar increased pattern according to severity of AECOPD endotypes. Conclusion:
      In COPD exacerbation, the inflammatory markers show different increases in each
      COPD endotypes. These findings may be crucial for defining exacerbation
      endotypes, the severity of exacerbation, and treatment response during follow-up
      in COPD patients.

PMID- 30233161
TI  - mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator
      1alpha, tumor necrosis factor-alpha, and interleukin-6 in paraspinal muscles of
      patients with lumbar kyphosis: a preliminary study.
AB  - Background: Kyphosis is a spine deformity that can lead to falls and reduced
      quality of life. Peroxisome proliferator-activated receptor gamma coactivator
      1alpha (PGC-1alpha) regulates mitochondrial biogenesis and is important for
      proper functioning of skeletal muscle, including the paraspinal muscles, which
      support and allow movement of the spine. The role of PGC-1alpha in paraspinal
      muscles in lumbar kyphosis has not been examined. We also examined the
      expressions of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha
      and interleukin (IL)-6. Methods: We obtained paraspinal muscle specimens from 12
      patients who underwent posterior lumbar surgery. RNA was isolated from these
      samples, and quantitative PCR was performed to compare the expression levels of
      PGC-1alpha, TNF-alpha, and IL-6 mRNA between patients with decreased lumbar
      lordosis (LL) and normal LL patients. Results: TNF-alpha and IL-6 mRNA
      expressions in paraspinal muscles were significantly higher in the decreased LL
      group than in the normal LL group (P=0.048 for both). PGC-1alpha mRNA expression
      was slightly increased in the decreased LL group, but the difference was not
      significant. Age was significantly positively correlated with PGC-1alpha mRNA
      expression (P=0.010). PGC-1alpha mRNA expression was significantly positively
      correlated with TNF-alpha mRNA expression (P=0.022). LL was significantly
      negatively correlated with PGC-1alpha, TNF-alpha, and IL-6 mRNA expressions
      (P=0.015, 0.036, and 0.010, respectively). Conclusion: TNF-alpha and IL-6 mRNA
      expressions in paraspinal muscles were significantly higher in the decreased LL
      group than in the normal LL group. LL was significantly negatively correlated
      with PGC-1alpha, TNF-alpha, and IL-6 mRNA expressions. PGC-1alpha mRNA expression
      levels in paraspinal muscles may be affected by lumbar kyphosis.

PMID- 30233163
TI  - Life-Space mobility and clinical outcomes in COPD.
AB  - Background: Social isolation is a common experience in patients with COPD but is
      not captured by existing patient-reported outcomes, and its association with
      clinical outcomes is unknown. Methods: We prospectively enrolled adults with
      stable COPD who completed the University of Alabama at Birmingham Life Space
      Assessment (LSA) (range: 0-120, restricted Life-Space mobility: <=60 and a marker
      of social isolation in older adults); six-minute walk test (6MWT), and the
      University of California at San Diego Shortness of Breath Questionnaire, COPD
      Assessment Test, and Hospital Anxiety and Depression Scale. The occurrence of
      severe exacerbations (emergency room visit or hospitalization) was recorded by
      review of the electronic record up to 1 year after enrollment. We determined
      associations between Life-Space mobility and clinical outcomes using regression
      analyses. Results: Fifty subjects had a mean +/- SD %-predicted FEV1 of 42.9+/
      15.5, and 23 (46%) had restricted Life-Space mobility. After adjusting for age,
      gender, %-predicted FEV1, comorbidity count, inhaled corticosteroid/long-acting
      beta2-agonist use, and prior cardiopulmonary rehabilitation, subjects with
      restricted Life-Space had an increased risk for severe exacerbations (adjusted
      incidence rate ratio 4.65, 95% CI 1.19-18.23, P=0.03). LSA scores were associated
      with 6MWD (R=0.50, P<0.001), dyspnea (R=-0.58, P<0.001), quality of life (R=
      0.34, P=0.02), and depressive symptoms (R=-0.39, P=0.005). Conclusion: Restricted
      Life-Space mobility predicts severe exacerbations and is associated with reduced
      exercise tolerance, more severe dyspnea, reduced quality of life, and greater
      depressive symptoms.

PMID- 30233165
TI  - A case scenario study for the assessment of physician's behavior in the
      management of COPD: the WHY study.
AB  - Purpose: COPD diagnosis is mainly based on clinical judgment of physicians.
      Physicians do not also refer to COPD guidelines in their daily practice. This
      study aimed to assess attitudes of physicians regarding COPD diagnosis,
      treatment, and follow-up and to identify the factors influencing physicians'
      decisions in clinical practice. Patients and methods: Fifty physicians were
      selected from 12 EuroStat NUTS 2 regions and asked to assess seven fictitious
      case scenarios. The following five scenarios described patients with COPD: Case
      Global Initiative for Chronic Obstructive Lung Disease (GOLD) A-smoker and Case
      GOLD A-nonsmoker were previously undiagnosed patients presenting with dyspnea,
      Case GOLD D-smoker and GOLD B-exsmoker were COPD patients presenting with
      exacerbation, Case GOLD B-smoker was a previously diagnosed COPD patient with
      dyspnea in stable phase, Case asthma-COPD overlap syndrome, and Case obesity
      hypoventilation syndrome. Patients' history, physical examination findings,
      pulmonary function tests, and X-ray images were prepared before the study by an
      experts' committee and provided to the physicians upon their request, until they
      reached a final decision. The physicians completed a questionnaire including
      information about their clinical practices and institutions. Results: According
      to the GOLD 2015 recommendations, of the physicians, 44% performed guideline
      concordant diagnosis in the first five scenarios, who were all COPD patients, and
      6% performed guideline-concordant diagnosis in all cases. There was a negative
      correlation between high workload and making a guideline-concordant diagnosis
      (P=0.038, rho =-0.417). Even when the physicians made a guideline-concordant
      diagnosis of COPD, only a minority (10%-22%) used the GOLD classification.
      Logistic regression analysis revealed that working in a tertiary health care
      center was a significant factor in favor of establishing a guideline-concordant
      diagnosis of COPD (P=0.029, OR =6.139 [95% CI: 1.20-31.32]). Conclusion:
      Management of COPD patients in Turkey does not generally follow the GOLD criteria
      but is rather based on physicians' clinical experience. Heavy workload appears to
      adversely affect the correctness of clinical decisions.

PMID- 30233167
TI  - COPD: understanding patients' adherence to inhaled medications.
AB  - Background and objective: Adherence to inhaled medications by COPD patients is a
      challenging issue, but relatively understudied. The aim of this study is the
      characterization of adherence to inhaled medications by COPD patients, with a
      focus on patient-related determinants. Methods: Stable COPD outpatients >=40
      years of age from a respiratory unit and diagnosed according to the Global
      Initiative for Chronic Obstructive Lung Disease criteria were included in a cross
      sectional study. The Measure of Treatment Adherence (MTA), the Beliefs about
      Medications Questionnaire (BMQ) and demographic, clinical, and COPD
      questionnaires were used. After completing these questionnaires, semi-structured
      interviews were carried out and participants were encouraged to justify their
      opinions and behaviors. Field notes were made during the interviews and each
      interview was analyzed before the next one. Quantitative and qualitative analyses
      of the variables were then performed. Results: A total of 300 out of 319
      participants (mean age =67.7 years, 78.1% males) completed the MTA questionnaire.
      Of these, 31.3% were considered poorly adherent and 16.7% as non-adherent to the
      inhaled therapy. A statistically significant negative association was found
      between adherence and current smoking status (P=0.044), and between adherence and
      FEV1% (P=0.000). The mean BMQ Necessity score was higher in adherent patients
      (P=0.000), but the the mean Concern score was similar for both (P=0.877). We
      found nine patterns of poor-adherence, six reasons given for poor-adherence
      behaviors, five reasons for good-adherence behaviors and three patient-related
      domains on adherence to medications. Conclusion: Adherence is related to need
      perception and to the functional severity of the disease. A non-adherent patient
      is usually a current smoker with lower degree of airflow limitation and lower
      perception of medication necessity. New information obtained was related to the
      patterns and reasons for different adherence behaviors, which are based on three
      major groups of patient related-determinants: health-related experiences, health
      related behaviors and health-related beliefs.

PMID- 30233166
TI  - Prevalence of undiagnosed COPD in male patients with coronary artery disease: a
      cross-sectional study in Jordan.
AB  - Purpose: COPD and coronary artery disease (CAD) are common chronic diseases with
      shared risk factors. COPD continues to be largely underdiagnosed and
      undertreated. We aimed to describe the prevalence and predictors of undiagnosed
      COPD in Jordanian men with CAD. Patients and methods: In a cross-sectional study
      conducted at a referral center in Jordan, male patients who underwent coronary
      angiography for suspected CAD and reported $10 pack-year of cigarette smoking
      were recruited. Pre- and post-bronchodilator spirometry was undertaken for all
      participants, and COPD was defined as post-bronchodilator FEV1/FVC <70%. The
      finding of >=50% coronary luminal narrowing confirmed the presence of CAD.
      Results: Spirometry was undertaken for 376 men with mean age of 56.02+/-10.55
      years, and 72.6% were active cigarettes smokers with a mean pack-year of 55.89+/
      34.25. A CAD diagnosis was confirmed in 300 (79.8%) men. Spirometric criteria for
      COPD were met in 76 (15.7%) patients, of whom 91.5% were not previously
      diagnosed. COPD-related symptoms were common: chronic cough (44.4%), dyspnea
      (66.2%), and wheezes (27.9%). COPD was more common in patients with (18.0%)
      compared to patients without (6.6%) CAD (P=0.014). Multivariate logistic
      regression showed that the risk of COPD was higher in patients with CAD (OR 3.16,
      95% CI, 1.10-9.09, P=0.033) and in those with chronic bronchitis (OR 13.07, 95%
      CI, 6.69-25.52, P<0.001). Conclusion: There was a high prevalence of COPD among
      male patients with CAD and most were underdiagnosed despite having respiratory
      symptoms. Male smokers with CAD and respiratory symptoms should be evaluated for
      airflow limitation and the presence of COPD.

PMID- 30233168
TI  - Blood eosinophils and inhaled corticosteroids in patients with COPD: systematic
      review and meta-analysis.
AB  - Background: COPD is a highly heterogeneous disease. Potential biomarkers to
      identify patients with COPD who will derive the greatest benefit from inhaled
      corticosteroid (ICS) treatment are needed. Blood eosinophil count can serve as a
      predictive biomarker for the efficacy of ICS treatment. The aim of this
      systematic review and meta-analysis was to assess whether a blood eosinophil
      count of >=2% in patients undergoing ICS therapy was associated with a greater
      reduction in COPD exacerbation rate and pneumonia incidence. Materials and
      methods: An electronic search was performed using the keywords "COPD",
      "eosinophil", and "clinical trial" in the PubMed and EMBASE databases to retrieve
      articles, up to 2017, relevant to our focus. Data were extracted, and a meta
      analysis was conducted using RevMan 5 (version 5.3.5). Results: Five studies
      comprising 12,496 patients with moderate-to-very severe COPD were included. At
      baseline, 60% of the patients had >=2% blood eosinophils. Our meta-analysis
      showed a 17% reduction in exacerbation of moderate/severe COPD in patients with
      >=2% blood eosinophils undergoing ICS therapy compared to the non-ICS/ICS
      withdrawal/placebo group. The difference between the two types of treatment was
      significant (risk ratio [RR], 0.816; 95% CI, 0.67-0.99; P=0.03). Furthermore, the
      risk of pneumonia-related events was significantly increased in the subgroup with
      eosinophil count >=2% undergoing ICS-containing treatments (RR, 1.969; 95% CI,
      1.369-2.833; P<0.001). There was no significant difference in the subgroup with
      eosinophil count <2% (RR, 1.29; 95% CI, 0.888-1.879; P<0.181). Conclusion: The
      results of our meta-analysis suggest that the 2% threshold for blood eosinophils
      could accurately predict ICS treatment response in patients with COPD, but
      increased the risk of pneumonia.

PMID- 30233169
TI  - Functional performance in patients with COPD: association with treatment regimen,
      GOLD group, lung function, and symptom burden in a cross-sectional study.
AB  - Background: Data suggesting that low physical activity levels are associated with
      increased mortality and exacerbations in patients with COPD have led to
      increasing interest in the role of physical activity in COPD. This study
      evaluated self-reported functional performance, a measure of physical activity
      impairment, according to current treatment regimen, lung function, symptoms, and
      Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 groups in a
      large sample of patients with COPD. Methods: This multicenter, cross-sectional,
      observational study (study identifier: D5970R00003) included patients with COPD
      (>=40 years) in the USA. A self-completion questionnaire captured demographics
      and patient-reported outcomes, including the Functional Performance Inventory
      Short Form (FPI-SF). Diagnosis and treatment history (including spirometry
      results) were extracted from medical charts. Multiple linear regression was used
      to determine the relationship between FPI-SF and FEV1 % predicted, and FPI-SF and
      COPD assessment test (CAT) score. Results: Overall, 1,775 patients participated
      (classified as GOLD 2017 group A, 14.8%; B, 46.6%; C, 2.6%; D, 36.0%). Physical
      activity impairment affected patients across all treatment regimens and GOLD
      groups (mean FPI-SF total score: 2.1), with the greatest impairment within FPI-SF
      observed for domains requiring most physical exertion, "physical exercise" and
      "maintaining the household" (mean FPI-SF scores: 1.7 and 1.8, respectively).
      Patients receiving loose triple therapy and those in GOLD group D had the highest
      impairment (mean FPI-SF total scores: both 1.9), and the lowest FEV1 % predicted
      (55.5% and 54.7%, respectively). FPI-SF total score correlated with FEV1 %
      predicted and more strongly with CAT score (all P<0.05). Conclusion: The stronger
      correlation between FPI-SF and CAT scores compared to FPI-SF and FEV1 % predicted
      suggests that symptoms may have a greater impact on patients' functional
      performance than lung function. Further longitudinal studies are required to
      establish a correlation between the effect of treatment on symptoms, lung
      function, and physical activity.

PMID- 30233164
TI  - A time for everything and everything in its time - exploring the mechanisms
      underlying seasonality of COPD exacerbations.
AB  - Across Europe, COPD affects 23 million people leading to annual health care costs
      of ~?25.1 billion. This burden is particularly severe during winter months in
      association with the peak incidence of exacerbation events. Seasonal variation in
      the health status of patients with COPD places additional and often critical
      pressure on already strained health care resources. COPD exacerbations are
      characterized by worsening day-to-day symptoms of an individual and often
      triggered by respiratory infections, but the process by which this occurs in a
      seasonal fashion is likely to be multifactorial. In this review, we discuss
      recent population studies that highlight the impact of seasonality in COPD and
      review the proposed biological mechanisms underlying this. An appraisal of the
      role of the host susceptibility and response, environmental triggers and the
      biology of respiratory pathogens is detailed. The impact of each aspect is
      considered, and an integrated model of the context for the whole individual and
      society in general is explored.

PMID- 30233171
TI  - New developments in optimizing bronchodilator treatment of COPD: a focus on
      glycopyrrolate/formoterol combination formulated by co-suspension delivery
      technology.
AB  - COPD causes considerable health and economic burden worldwide, with incidence of
      the disease expected to continue to rise. Inhaled bronchodilators, such as long
      acting muscarinic antagonists (LAMAs) and long-acting beta2-agonists (LABAs), are
      central to the maintenance treatment of patients with COPD. Clinical studies have
      demonstrated that combined LAMA + LABA therapies improve efficacy while retaining
      a safety profile similar to LAMA or LABA alone. This has led to the development
      of several LAMA/LABA fixed-dose combination (FDC) therapies, which provide
      patients with the convenience of two active compounds in a single inhaler. GFF
      MDI (Bevespi Aerosphere(r)) is an FDC of glycopyrrolate/formoterol fumarate
      18/9.6 ug formulated using innovative co-suspension delivery technology for
      administration via metered dose inhaler (MDI). GFF MDI was developed to make a
      treatment option available for patients who have a requirement or preference to
      use an MDI, rather than a dry powder or soft mist inhaler. Now that several
      LAMA/LABA FDCs have been approved for use in COPD, we review the impact of dual
      bronchodilator treatment on COPD therapy and discuss recent clinical studies that
      are helping to develop a more comprehensive understanding of how LAMA/LABA FDCs
      can improve patient outcomes.

PMID- 30233172
TI  - Micro-/nano-topography of selective laser melting titanium enhances adhesion and
      proliferation and regulates adhesion-related gene expressions of human gingival
      fibroblasts and human gingival epithelial cells.
AB  - Background: Selective laser melting (SLM) titanium is an ideal option to
      manufacture customized implants with suitable surface modification to improve its
      bioactivity. The peri-implant soft tissues form a protective tissue barrier for
      the underlying osseointegration. Therefore, original microrough SLM surfaces
      should be treated for favorable attachment of surrounding soft tissues. Material
      and methods: In this study, anodic oxidation (AO) was applied on the microrough
      SLM titanium substrate to form TiO2 nanotube arrays. After that, calcium
      phosphate (CaP) nanoparticles were embedded into the nanotubes or the interval of
      nanotubes by electrochemical deposition (AOC). These two samples were compared to
      untreated (SLM) samples and accepted mechanically polished (MP) SLM titanium
      samples. Scanning electron microscopy, energy dispersive spectrometry, X-ray
      diffraction, surface roughness, and water contact angle measurements were used
      for surface characterization. The primary human gingival epithelial cells (HGECs)
      and human gingival fibroblasts (HGFs) were cultured for cell assays to determine
      adhesion, proliferation, and adhesion-related gene expressions. Results: For
      HGECs, AOC samples showed significantly higher adhesion, proliferation, and
      adhesion-related gene expressions than AO and SLM samples (P<0.05) and similar
      exceptional ability in above aspects to MP samples. At the same time, AOC samples
      showed the highest adhesion, proliferation, and adhesion-related gene expressions
      for HGFs (P<0.05). Conclusion: By comparison between each sample, we could
      confirm that both anodic oxidation and CaP nanoparticles had improved
      bioactivity, and their combined utilization may likely be superior to mechanical
      polishing, which is most commonly used and widely accepted. Our results indicated
      that creating appropriate micro-/nano-topographies can be an effective method to
      affect cell behavior and increase the stability of the peri-implant mucosal
      barrier on SLM titanium surfaces, which contributes to its application in dental
      and other biomedical implants.

PMID- 30233174
TI  - In vitro cellular localization and efficient accumulation of fluorescently tagged
      biomaterials from monodispersed chitosan nanoparticles for elucidation of
      controlled release pathways for drug delivery systems.
AB  - Background: Inefficient cellular delivery and poor intracellular accumulation are
      major drawbacks towards achieving favorable therapeutic responses from many
      therapeutic drugs and biomolecules. To tackle this issue, nanoparticle-mediated
      delivery vectors have been aptly explored as a promising delivery strategy
      capable of enhancing the cellular localization of biomolecules and improve their
      therapeutic efficacies. However, the dynamics of intracellular biomolecule
      release and accumulation from such nanoparticle systems has currently remained
      scarcely studied. Objectives: The objective of this study was to utilize a
      chitosan-based nanoparticle system as the delivery carrier for glutamic acid, a
      model for encapsulated biomolecules to visualize the in vitro release and
      accumulation of the encapsulated glutamic acid from chitosan nanoparticle (CNP)
      systems. Methods: CNP was synthesized via ionic gelation routes utilizing
      tripolyphosphate (TPP) as a cross-linker. In order to track glutamic acid
      release, the glutamic acid was fluorescently-labeled with fluorescein
      isothiocyanate prior encapsulation into CNP. Results: Light Scattering data
      concluded the successful formation of small-sized and mono-dispersed CNP at a
      specific volume ratio of chitosan to TPP. Encapsulation of glutamic acid as a
      model cargo into CNP led to an increase in particle size to >100 nm. The
      synthesized CNP exhibited spherical shape under Electron Microscopy. The
      formation of CNP was reflected by the reduction in free amine groups of chitosan
      following ionic crosslinking reactions. The encapsulation of glutamic acid was
      further confirmed by Fourier Transform Infrared (FTIR) analysis. Cell viability
      assay showed 70% cell viability at the maximum concentration of 0.5 mg/mL CS and
      0.7 mg/mL TPP used, indicating the low inherent toxicity property of this system.
      In vitro release study using fluorescently-tagged glutamic acids demonstrated the
      release and accumulation of the encapsulated glutamic acids at 6 hours post
      treatment. A significant accumulation was observed at 24 hours and 48 hours
      later. Flow cytometry data demonstrated a gradual increase in intracellular
      fluorescence signal from 30 minutes to 48 hours post treatment with fluorescently
      labeled glutamic acids encapsulated CNP. Conclusion: These results therefore
      suggested the potential of CNP system towards enhancing the intracellular
      delivery and release of the encapsulated glutamic acids. This CNP system thus may
      serves as a potential candidate vector capable to improve the therapeutic
      efficacy for drugs and biomolecules in medical as well as pharmaceutical
      applications through the enhanced intracellular release and accumulation of the
      encapsulated cargo.

PMID- 30233175
TI  - Quercetin and doxorubicin co-delivery using mesoporous silica nanoparticles
      enhance the efficacy of gastric carcinoma chemotherapy.
AB  - Background: Effective gastric carcinoma (GC) chemotherapy is subject to many in
      vitro and in vivo barriers, such as tumor microenvironment and multidrug
      resistance. Materials and methods: Herein, we developed a hyaluronic acid (HA)
      modified silica nanoparticle (HA-SiLN/QD) co-delivering quercetin and doxorubicin
      (DOX) to enhance the efficacy of GC therapy (HA-SiLN/QD). The HA modification was
      done to recognize overexpressed CD44 receptors on GC cells and mediate selective
      tumor targeting. In parallel, quercetin delivery decreased the expression of
      Wnt16 and P-glycoprotein, thus remodeling the tumor microenvironment and reversed
      multidrug resistance to facilitate DOX activity. Results: Experimental results
      demonstrated that HA-SiLN/QD was nanoscaled particles with preferable stability
      and sustained release property. In vitro cell experiments on SGC7901/ADR cells
      showed selective uptake and increased DOX retention as compared to the DOX mono
      delivery system (HA-SiLN/D). Conclusion: In vivo anticancer assays on the
      SGC7901/ADR tumor-bearing mice model also revealed significantly enhanced
      efficacy of HA-SiLN/QD than mono-delivery systems (HA-SiLN/Q and HA-SiLN/D).

PMID- 30233173
TI  - Amelioration effects of nanoencapsulated triterpenoids from petri dish-cultured
      Antrodia cinnamomea on reproductive function of diabetic male rats.
AB  - Purpose: Nanoencapsulated triterpenoids from petri dish-cultured Antrodia
      cinnamomea (PAC) and its amelioration effects on reproductive function in
      diabetic rats were investigated. Materials and methods: PAC encapsulated in
      silica-chitosan nanoparticles (Nano-PAC) was prepared by the biosilicification
      method. The diabetic condition in male Sprague Dawley rats was induced by high
      fat diet and streptozotocin (STZ). Three different doses of Nano-PAC (4, 8, and
      20 mg/kg) were administered for 6 weeks. Metformin and control of nanoparticles
      (Nano-con) were taken as positive and negative controls, respectively. Results:
      The average particle size was ~79.46+/-1.63 nm, and encapsulation efficiency was
      ~73.35%+/-0.09%. Nano-PAC administration improved hyperglycemia and insulin
      resistance. In addition, Nano-PAC ameliorated the morphology of testicular
      seminiferous tubules, sperm morphology, motility, ROS production, and
      mitochondrial membrane potential. Superoxide dismutase (SOD), glutathione
      peroxidase (GPx), and catalase (CAT) antioxidant, as well as testosterone,
      luteinizing hormone (LH), and follicle stimulating hormone (FSH) were increased,
      whereas proinflammatory cytokines TNF-alpha, IL-6, and IFN-gamma were decreased.
      Conclusion: In the present study, we successfully nanoencapsulated PAC and found
      that a very low dosage of Nano-PAC exhibited amelioration effects on the
      reproductive function of diabetic rats.

PMID- 30233176
TI  - Synthesis and characterization of a novel peptide-grafted Cs and evaluation of
      its nanoparticles for the oral delivery of insulin, in vitro, and in vivo study.
AB  - Background: Despite years of experience and rigorous research, injectable insulin
      is the sole trusted treatment method to control the blood glucose level in
      diabetes type 1 patients, but injection of insulin is painful and poses a lot of
      stress to the patients, especially children, therefore, development of a non
      injectable formulation of insulin is a major breakthrough in the history of
      medicine and pharmaceutical sciences. Methods: In this study, a novel peptide
      grafted derivative of chitosan (CPP-g- chitosan) is synthesized and its potential
      for oral delivery of proteins and peptides is evaluated. Drug-loaded
      nanoparticles were developed from this derivative using ionic gelation method
      with application of sodium tripolyphosphate (TPP) as a cross-linking agent. Human
      insulin was used as the model protein drug and release kinetic was studied at
      gastrointestinal pH. Finally the developed nanoparticles were filled into very
      tiny enteric protective capsules and its effects on blood glucose level are
      evaluated in laboratory animals. Results: Presence of the positively charged cell
      penetrating peptide moiety in the structure of chitosan polymer had slight
      inhibitory effects on the release of insulin from the nanoparticles in simulated
      gastric fluid (pH 1.2) comparing to native chitosan. The nanoparticles were
      positively charged in gastrointestinal pH with size ranging from 180 nm to 326
      nm. The polypeptide grafted to chitosan is a novel analog of Penetratin,
      presenting both the hydrophilic and hydrophobic characteristics altering the
      release behavior of the nanoparticles and significantly increase the absorption
      of insulin into the rat epithelium comparing to nanoparticles from simple
      chitosan. In-vivo results in diabetic rat proved that this nanoparticulate system
      can significantly lower the blood glucose levels in diabetic rats and remain
      effective for a duration of 9-11 hours. Conclusion: The results indicate that
      nanoparticles developed from this new peptide conjugated derivative of chitosan
      are very promising for oral delivery of proteins and peptides.

PMID- 30233178
TI  - In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules.
AB  - Background: Toxicity of nanomaterials is one of the most important factors
      limiting their medical application. Evaluation of in vitro nanotoxicity allows
      for the identification and elimination of most of the toxic materials prior to
      animal testing. The current knowledge of the possible side effects of
      biodegradable nanomaterials, such as liposomes and polymeric organic
      nanoparticles, is limited. Previously, we developed a potential drug delivery
      system in the form of nanocapsules with polyelectrolyte, biodegradable shells
      consisting of poly-l-lysine and poly-l-glutamic acid (PGA), formed by the layer
      by-layer adsorption technique. Methods: Hemolysis assay, viability tests, flow
      cytometry analysis of vascular cell adhesion molecule-1 expression on
      endothelium, analysis of nitric oxide production, measurement of intracellular
      reactive oxygen species levels, detection of antioxidant enzyme activity, and
      analysis of DNA damage with comet assay were performed to study the in vitro
      toxicity of nanocapsules. Results: In this work, we present the results of an in
      vitro analysis of toxicity of five-layer positively charged poly-l-lysine
      terminated nanocapsules (NC5), six-layer negatively charged PGA-terminated
      nanocapsules (NC6) and five-layer PEGylated nanocapsules (NC5-PEG). PGA and
      polyethylene glycol (PEG) were used as two different "stealth" polymers. Of all
      the polyelectrolyte nanocapsules tested for blood compatibility, only cationic
      NC5 showed acute toxicity toward blood cells, expressed as hemolysis and
      aggregation. Neither NC6 nor NC5-PEG had proinflammatory activity evaluated
      through changes in the expression of NF-kappaB-dependent genes, iNOS and vascular
      cell adhesion molecule-1, induced oxidative stress, or promoted DNA damage in
      various cells. Conclusion: Our studies clearly indicate that PGA-coated
      (negatively charged) and PEGylated polyelectrolyte nanocapsules do not show in
      vitro toxicity, and their potential as a drug delivery system may be safely
      studied in vivo.

PMID- 30233170
TI  - Prevalence of smoking in a psychiatric hospital and its relationship with
      respiratory symptoms and the prevalence of COPD.
AB  - Purpose: Psychiatric patients present an elevated rate of smoking, and the
      smoking habit is related to a high morbidity and mortality in this collective.
      The aim of this study was to determine the prevalence of smoking in patients
      admitted for psychiatric disorders and its relationship with respiratory disease,
      the prevalence of COPD, and alterations in the quality of life. Patients and
      methods: A cross-sectional, observational study was conducted and detailed
      information on smoking and respiratory symptomatology was obtained. The study
      participants underwent the following tests: spirometry with bronchodilator test,
      Fagerstrom test, determination of physical activity using the LCADL
      questionnaire, and evaluation of quality of life with the EuroQoL-5 Dimensions EQ
      5D questionnaire. Results: Two hundred seventy-six patients (mean age 56.8 years)
      were included: 155 with schizophrenia (87.7% smokers), 46 with depressive or
      anxiety disorders (54.3% smokers), and 49 and 25 with intellectual disability and
      dementia (43.2% smokers), respectively. The mean Fagerstrom test score was 5.75
      points. Smokers presented with cough (47.6%), expectoration (41.4%), and chronic
      bronchitis (36.6%). The prevalence of COPD in the total population was 28.9%. The
      EQ-5D and LCADL scores were better in smokers because of their younger age and
      lesser psychiatric involvement. A high prevalence of smoking was observed in the
      psychiatric population studied, and 28.9% were diagnosed with COPD. Conclusion:
      Smokers presented many more respiratory symptoms and chronic bronchitis but did
      not present a worse quality of life or physical activity due to their younger age
      and milder psychiatric involvement.

PMID- 30233180
TI  - Anti-JNK2 peptide-siRNA nanostructures improve plaque endothelium and reduce
      thrombotic risk in atherosclerotic mice.
AB  - Background: A direct and independent role of inflammation in atherothrombosis was
      recently highlighted by the Canakinumab Antiinflammatory Thrombosis Outcome Study
      (CANTOS) trial, showing the benefit of inhibiting signaling molecules, eg,
      interleukins. Accordingly, we sought to devise a flexible platform for preventing
      the inflammatory drivers at their source to preserve plaque endothelium and
      mitigate procoagulant risk. Methods: p5RHH-siRNA nanoparticles were formulated
      through self-assembly processes. The therapeutic efficacy of p5RHH-JNK2 siRNA
      nanoparticles was evaluated both in vitro and in vivo. Results: Because JNK2 is
      critical to macrophage uptake of oxidized lipids through scavenger receptors that
      engender expression of myriad inflammatory molecules, we designed an RNA
      silencing approach based on peptide-siRNA nanoparticles (p5RHH-siRNA) that
      localize to atherosclerotic plaques exhibiting disrupted endothelial barriers to
      achieve control of JNK2 expression by macrophages. After seven doses of p5RHH
      JNK2 siRNA nanoparticles over 3.5 weeks in ApoE-/- mice on a Western diet, both
      JNK2 mRNA and protein levels were significantly decreased by 26% (P=0.044) and
      42% (P=0.042), respectively. Plaque-macrophage populations were markedly depleted
      and NFkappaB and STAT3-signaling pathways inhibited by 47% (P<0.001) and 46%
      (P=0.004), respectively. Endothelial barrier integrity was restored (2.6-fold
      reduced permeability to circulating 200 nm nanoparticles in vivo, P=0.003) and
      thrombotic risk attenuated (200% increased clotting times to carotid artery
      injury, P=0.02), despite blood-cholesterol levels persistently exceeding 1,000
      mg/dL. No adaptive or innate immunoresponses toward the nanoparticles were
      observed, and blood tests after the completion of treatment confirmed the largely
      nontoxic nature of this approach. Conclusion: The ability to formulate these
      nanostructures rapidly and easily interchange or multiplex their oligonucleotide
      content represents a promising approach for controlling deleterious signaling
      events locally in advanced atherosclerosis.

PMID- 30233179
TI  - Facilitated permeation of insulin across TR146 cells by cholic acid derivatives
      modified elastic bilosomes.
AB  - Background: Buccal delivery of insulin is still a challenging issue for the
      researchers due to the presence of permeability barrier (buccal mucosa) in the
      buccal cavity. The main objective of this study was to investigate the safety,
      effectiveness, and potential of various liposomes containing different bile salts
      to improve the permeation of insulin across in vitro TR146 buccal cell layers.
      Methods: Elastic bilosomes containing soy lecithin and bile salt edge activators
      (sodium cholate [SC], sodium taurocholate [STC], sodium glycocholate [SGC],
      sodium deoxyglycocholate [SDGC], or sodium deoxytaurocholate [SDTC]) were
      fabricated by thin-film hydration method. The prepared liposomes were
      characterized, and in vitro permeation studies were performed. The fluorescein
      isothiocyanate-insulin-loaded elastic bilosomes were used to evaluate the
      quantitative and qualitative cellular uptake studies. Results: The prepared
      elastic bilosomes had a particle size and an entrapment efficiency of ~140-150 nm
      and 66%-78%, respectively. SDGC-lipo (SDGC-incorporated liposome) was observed to
      be the most superior with an enhancement ratio (ER) of 5.24 (P<0.001). The SC
      incorporated liposome (SC-lipo) and SDTC-incorporated liposome (SDTC-lipo) also
      led to a significant enhancement with ERs of 3.20 and 3.10 (P<0.05),
      respectively, compared with insulin solution. These results were further
      supported by quantitative and qualitative cellular uptake studies performed
      employing fluorescence-activated cell sorting analysis and confocal microscopy,
      respectively. The relative median fluorescence intensity values of elastic
      bilosomes were counted in the order of SDGC-lipo > SC-lipo > SDTC-lipo > SGC
      incorporated liposome > STC-incorporated liposome, and similarity in the
      permeability profile of the employed elastic bilosomes was noted. Conclusion:
      This study presents the employment of various derivatives of cholic acid-loaded
      elastic bilosomes as a promising strategy to enhance the permeation of insulin
      through buccal route.

PMID- 30233181
TI  - Effect of melanin on gold nanoparticle-induced hepatotoxicity and lipid
      peroxidation in rats.
AB  - Introduction: Melanin pigments are produced by melanocytes and are believed to
      act as antioxidants based on the belief that melanin can suppress electronically
      stirred states and scavenge the free radicals. Materials and methods: The study
      was aimed to verify and prove the toxicity induced by administration of gold
      nanoparticles (GNPs) and to characterize the role of melanin as an antioxidant
      against inflammatory liver damage, oxidative stress, and lipid peroxidation
      induced intraperitoneally by GNPs in vivo. Results: The findings from this study
      confirmed that administration of GNPs intraperitoneally caused liver damage in
      addition to producing oxidative stress and fatty acid peroxidation. The treatment
      of rats with melanin along with GNPs induced dramatic changes in all the measured
      biochemical parameters. Our data demonstrated that melanin completely inhibited
      inflammatory liver damage, oxidative stress, and lipid peroxidation, which was
      confirmed by the histological investigation of different liver sections stained
      by H&E. Conclusion: These results suggest the beneficial use of melanin together
      with GNPs for alleviating its toxicity. Other studies should be implemented
      taking into consideration the role of melanin in comparison with other natural
      antioxidants.

PMID- 30233183
TI  - Vulnerability or resilience of motopsin knockout mice to maternal separation
      stress depending on adulthood behaviors.
AB  - Background: Both environmental and genetic conditions contribute to the robust
      development of neuronal circuits and adulthood behaviors. Loss of motopsin gene
      function causes severe intellectual disability in humans and enhanced social
      behavior in mice. Furthermore, childhood maltreatment is a risk factor for some
      psychiatric disorders, and children with disabilities have a higher risk of abuse
      than healthy children. Materials and methods: In this study, we investigated the
      effects of maternal separation (MS) on adulthood behaviors of motopsin knockout
      (KO) and wild-type (WT) mice. Results: The MS paradigm decreased the duration
      that WT mice stayed in the center area of an open field, but not for motopsin KO
      mice; however, it decreased the novel object recognition index in both genotypes.
      In the marble burying test, motopsin KO mice buried fewer marbles than WT mice,
      regardless of the rearing conditions. The MS paradigm slightly increased and
      reduced open arm entry in the elevated plus maze by WT and motopsin KO mice,
      respectively. In the three-chamber test, the rate of sniffing the animal cage was
      increased by the MS paradigm only for motopsin KO mice. After the three-chamber
      test, motopsin KO mice had fewer cFos-positive cells in the prelimbic cortex,
      which is involved in emotional response, than WT mice. In the infralimbic cortex,
      the MS paradigm decreased the number of cFos-positive cells in motopsin KO mice.
      Conclusion: Our results suggest that motopsin deficiency and childhood adversity
      independently affect some behaviors, but they may interfere with each other for
      other behaviors. Defective neuronal circuits in the prefrontal cortex may add to
      this complexity.

PMID- 30233185
TI  - Do eyes with and without optic neuritis in multiple sclerosis age equally?
AB  - Purpose: Anterior visual pathway reflects axonal loss caused by both optic
      neuritis (ON) and neurodegeneration in multiple sclerosis (MS). Although the
      axonal injury post-ON is thought to be complete by 6 months of onset, most
      studies using optical coherence tomography (OCT) to evaluate retinal changes as a
      marker of neurodegeneration exclude eyes with a history of ON or consider them
      separately. The objective of this study was to assess whether the eyes post-ON
      (>6 months) show in later years different rate of chronic retinal changes than
      the fellow eyes not affected by ON. Patients and methods: Fifty-six patients with
      MS with a history of ON in one eye (ON eyes) and no ON in the fellow (FL) eye,
      who were followed by OCT for >2 years, were selected from a cohort of patients
      with MS. Paired eye analysis was performed. Results: Mean interval post-ON at
      baseline was 5.65 (SD 5.05) years. Mean length of follow-up by OCT was 4.57
      years. There was no statistical difference in absolute or relative thinning of
      retinal nerve fiber layer in peripapillary area between the ON and FL eyes.
      Conclusion: This study has shown that we do not need to exclude eyes with a
      history of ON from longitudinal studies of neurodegeneration in MS, provided that
      we use data outside of the frame of acute changes post-ON. Long-term changes of
      peripapillary retinal nerve fiber layer in ON and FL eyes are equal.

PMID- 30233184
TI  - Victimization and posttraumatic stress disorder in homeless women with mental
      illness are associated with depression, suicide, and quality of life.
AB  - Objective: This study aimed to determine the following: 1) the proportion of
      women in the homeless population with schizophrenia (SZ) or bipolar disorder
      (BD), in addition to the trajectory of their homelessness (ie, homelessness
      history, number of nights spent without home during the 180 past nights) and the
      characteristics of their illnesses compared to men (ie, illness severity, suicide
      risk, physical health status, and quality of life [QoL]); 2) whether these women
      were victimized more frequently than similarly situated men; 3) the impact of
      victimization on these women in terms of illness severity, suicide risk, physical
      health status, and QoL; and lastly 4) the differences and overlap of homeless
      women with SZ and BD. Methods: This study employed data at baseline from a
      multicenter randomized controlled trial conducted in the following four large
      French cities: Lille, Marseille, Paris, and Toulouse. Mobile mental health
      outreach teams recruited SZ/BD homeless patients in the street, emergency
      shelters, hospitals, and jails from August 2011 to April 2014. Evaluations were
      performed during face-to-face interviews by psychiatrists and research assistants
      in the offices of mobile mental health outreach teams that were located in the
      downtown area of each city. The quantitative data were analyzed using descriptive
      analyses, chi-square and Student's t-tests, generalized estimating equation
      regression models, and path analysis. Results: A total of 703 patients were
      included in this study. The proportion of women in the SZ/BD homeless population
      was 123/703 (17.5%). In this population, women were more likely than men to
      declare that they were subjected to physical or sexual assault during the past 6
      months, that they had been diagnosed with posttraumatic stress disorder (PTSD),
      and that they had experienced more severe depressive symptoms. Moreover, these
      women presented a higher suicide risk, worse physical health status, and lower
      QoL than similarly situated men. Homeless women with BD were more vulnerable than
      women with SZ. A path analysis revealed that PTSD and violent victimization might
      explain the higher levels of depression and suicide risk and the lower levels of
      physical health status and QoL in homeless women. Conclusion: SZ/BD homeless
      women experience more PTSD and victimization than men, which are both associated
      with poor clinical outcomes. These results confirm the vulnerability of homeless
      women in this high need population and should be considered by public health
      policy.

PMID- 30233187
TI  - Prescreening clinical trial volunteers using an online personality questionnaire.
AB  - Background: The cost of a clinical trial is affected by the efficiency of
      participant recruitment. It would be desirable to create a prescreening method
      that identifies appropriate candidates for full screening, in order to prevent
      inconvenience for both trial and volunteers. This study presents an online
      prescreening tool for this purpose. Methods: In order to facilitate recruitment
      of 24 individuals meeting the criteria for generalized anxiety disorder to a
      pharmacological functional magnetic resonance imaging trial, we created an online
      personality questionnaire that generated a personality profile for each
      respondent and screened for the trial's basic criteria. Results: Our online
      platform screened 6,293 people for anxious personality traits in 1 year. A total
      of 862 eligible individuals were identified through this route, each of whom
      automatically received an email invitation to contact the study team for further
      telephone screening, if interested. Of those, 266 individuals contacted the team
      and 173 were telephone screened, with 53 attending the study site for medical
      checks. Twenty-eight individuals were fully eligible, and 24 completed the trial.
      This permitted completion on time and on budget. Conclusion: Our online
      prescreening personality questionnaire platform did not remove the need for
      telephone screening or onsite medical checks, but increased the efficiency of
      recruitment through noninvasive identification of those meeting key requirements.
      Thus, our platform is a useful recruitment technique for clinical trials and is
      time-saving for both the trial and potential participants.

PMID- 30233186
TI  - Trajectories of callous-unemotional traits from childhood to adolescence in
      referred youth with a disruptive behavior disorder who received intensive
      multimodal therapy in childhood.
AB  - Purpose: Our aims were to explore the developmental trajectories of callous
      unemotional (CU) traits using a growth curve analysis in Italian children with
      disruptive behavior disorders treated with a multimodal intervention, and to test
      both predictors and distal outcomes of CU traits trajectories. Patients and
      method: One hundred and sixty-eight children were enrolled, of whom 24 were lost
      in the follow-up and 144 were followed up from ages 8-9 to 14-15 years with four
      assessment points. Patients included 128 males (88.9%) with a mean age of 8.7
      years, 96 with oppositional defiant disorder (66.7%) and 48 with conduct disorder
      (CD) (33.3%). The developmental trajectories of CU traits were assessed with the
      Inventory of Callous-Unemotional Traits (ICU). Results: Our findings revealed
      that CU features were likely to fit a quadratic model from childhood to
      adolescence. The CU traits tended to decrease during childhood, with
      stabilization in adolescence and a significant variability in the growth curves.
      Pretreatment CD and higher levels of externalizing behavioral problems were
      associated with higher level of CU traits at baseline, whereas positive parenting
      was associated with lower levels. No significant effects were found for all the
      other predictors (socioeconomic status, negative parenting, combined
      pharmacotherapy). Regarding outcomes into adolescence, both higher levels of CU
      traits at the baseline and a lower decrease of CU traits across time points
      predicted a higher risk of CD diagnosis, and higher rate of referrals to mental
      health services and of substance use. Furthermore, pretreatment CD and negative
      parenting predicted a higher risk of substance use into adolescence. Conclusion:
      Our findings suggest that a close monitoring of CU traits in referred children
      with disruptive behavior disorders may help to detect the patients at higher risk
      of poor outcome.

PMID- 30233188
TI  - Erratum: Children with autism spectrum disorders and selective mutism
      [Corrigendum].
AB  - [This corrects the article on p. 1163 in vol. 14, PMID: 29765220.].

PMID- 30233177
TI  - Folate-receptor-targeted laser-activable poly(lactide-co-glycolic acid)
      nanoparticles loaded with paclitaxel/indocyanine green for
      photoacoustic/ultrasound imaging and chemo/photothermal therapy.
AB  - Background: Cancer is one of the most serious threats to human health. Precision
      medicine is an innovative approach to treatment, as part of which theranostic
      nanomedicine has been studied extensively. However, the required biocompatibility
      and substantial cost for the approval of nanomedicines hinder their clinical
      translation. Purpose: We designed a novel type of theranostic nanoparticle (NP)
      folate-receptor-targeted laser-activatable poly(lactide-co-glycolic acid) (PLGA)
      NPs loaded with paclitaxel (Ptx)/indo-cyanine green (ICG)-folic acid-polyethylene
      glycol (PEG)-PLGA-Ptx@ICG-perfluorohexane (Pfh)- using safe and approved
      materials and drugs, which would facilitate clinical translation. With laser
      irradiation, highly efficient photothermal therapy can be achieved. Additionally,
      targeted NPs can be activated by near-infrared laser irradiation at a specific
      region, which leads to the sharp release of Ptx at areas of high folate-receptor
      expression and ensures a higher Ptx concentration within the tumor region,
      thereby leading to chemo/photothermal synergistic antitumor efficacy. Meanwhile,
      the NPs can be used as a dual-modality contrast agent for photoacoustic and
      ultrasound imaging. Materials and methods: FA-PEG-PLGA-Ptx@ICG-Pfh NPs were
      prepared by sonification method and characterized for physicochemical properties.
      Cytotoxicity and in vivo biocompatibility were evaluated respectively by CCK8
      assay and blood analysis. NPs as dual-modality contrast agents were evaluated by
      photoacoustic/ultrasound imaging system in vitro and in vivo. In vitro anticancer
      effect and in vivo anticancer therapy was evaluated by CCK8 assay and MDA-MB231
      tumor-bearing mice model. Results: FA-PEG-PLGA-Ptx@ICG-Pfh NPs were in the size
      of 308+/-5.82 nm with negative zeta potential and showed excellent photothermal
      effect. The NPs could be triggered sharp release of Ptx by laser irradiation, and
      showed the good biocompatibility in vitro and in vivo. Through
      photoacoustic/ultrasound imaging, the NPs showed an excellent ability as dual
      modality contrast agents in vitro and in vivo. FA-PEG-PLGA-Ptx@ICG-Pfh NPs with
      laser irradiation showed the best anticancer efficacy in vitro and in vivo.
      Conclusion: Such a biocompatible and novel theranostic NP is expected to
      integrate dual-modality imaging with improved therapeutic efficacy and provide a
      promising paradigm for cancer therapy.

PMID- 30233189
TI  - Increased serum levels of sortilin-derived propeptide after electroconvulsive
      therapy in treatment-resistant depressed patients.
AB  - Purpose: Sortilin-derived propeptide (PE) and its synthetic analog spadin show
      strong antidepressant activity in rodents and, therefore, could be used as a
      biomarker to evaluate the clinical efficacy of antidepressant treatments. The aim
      of this study was to determine whether electroconvulsive therapy (ECT) modulates
      serum PE concentration in patients with treatment-resistant depression (TRD).
      Patients and methods: Forty-five patients with major depressive disorder, who met
      the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, were
      selected for this study. Results: We did not observe any difference in the PE
      levels between TRD patients and controls (z=0.10, P=0.92), but we found a strong
      significant increase between the PE levels measured just before (T0) and about 1
      month (T2) after ECT (z=-2.82, P=0.005). A significant difference between T0 and
      T2 was observed only in responders (z=-2.59, P=0.01), whereas no effect was found
      in nonresponders (z=-1.27, P=0.20). Interestingly, we found a significant
      correlation between the increase in PE levels and decrease in Montgomery -Asberg
      Depression Rating Scale scores for the total patient sample (P=0.03). Conclusion:
      This study indicates for the first time that ECT affects serum PE concentration
      in responders and, therefore, could contribute to the evaluation of the therapy
      success.

PMID- 30233191
TI  - Durability of initial antidiabetic monotherapy and subsequent treatment
      adjustment patterns among newly treated type 2 diabetes patients.
AB  - Background: As newly available antidiabetic drugs (ADs) are used more commonly as
      initial hypoglycemic choice for early stage diabetes patients, there is an urgent
      need to investigate how these agents may differ in treatment durability relative
      to metformin. This study aimed to investigate the incidence and risk of treatment
      adjustment among newly treated type 2 diabetes mellitus (T2DM) patients receiving
      an oral AD as initial monotherapy. Methods: T2DM patients registered in the
      National Health Insurance Program who were newly prescribed an oral AD were
      identified. Time to treatment addition or switch to alternative antidiabetic
      therapy was determined using the Kaplan-Meier survival analysis. Cox proportional
      hazards regression was performed to estimate the hazard ratio (HR) after
      adjusting for potential confounding factors. Results: The median time to
      treatment adjustment was shorter for sulfonylureas (SUs), dipeptidyl peptidase-4
      (DPP-4) inhibitors, alphaglucosidase (AG) inhibitors, and thiazolidinediones
      (TZDs) compared to that for metformin. Initiation of therapy with SUs or DPP-4
      inhibitors was associated with a significantly higher risk of both treatment
      addition and switching than with metformin (HR 1.49 versus 1.47 for overall
      treatment adjustment, respectively). In contrast, among incident users of AG
      inhibitors or TZDs, only the hazard of switch was substantially increased
      compared to metformin starters (6.19, 95% confidence interval [CI] 5.77-6.64 and
      7.31, 95% CI 6.35-8.42, respectively). When addition and switch events were
      collectively assessed, the risk of treatment adjustment was significantly
      elevated in all non-metformin cohorts. Conclusion: Our results demonstrated that
      the durability of metformin as an initial monotherapy was superior to that of
      other ADs, including newer classes of antidiabetics, and appeared to be more
      effective in delaying treatment adjustment in real-world clinical practice.

PMID- 30233190
TI  - The outcome of pediatric patients undergoing congenital cardiac surgery under
      pulsatile cardiopulmonary bypass in different frequencies.
AB  - Purpose: To investigate the influence and possible pathophysiological mechanism
      of pulsatile cardiopulmonary bypass (CPB) in various frequencies in pediatric
      patients undergoing congenital cardiac surgery. Patients and methods: Clinical
      data and hemodynamic parameters were collected in 80 patients who underwent
      congenital cardiac surgeries and were perfused in different settings: pulsatile
      perfusion (PP) in frequencies of 30 beats/min, PP 60 beats/min, PP 100 beats/min
      and non-pulsatile perfusion (NP). Serum proteins, plasma-free hemoglobin (PFH),
      endothelin-1 (ET-1) and nitric oxide (NO) were collected to study possible
      pathophysiological changes, possible hematological injury and oxidative status
      under different perfusing conditions. Results: Patients in all groups had similar
      baseline characteristics, aortic cross-clamping time and CPB duration. More
      effective pulse gradient (PG), energy-equivalent pressure (EEP) and surplus
      hemodynamic energy (SHE) were observed in pulsatility with lower frequency
      setting, under which more patients achieved physiologically normal mean arterial
      pressure (MAP), without the support of inotropic agents during bypass.
      Significant between-group differences of serum proteins and PFH were absent the
      whole time during and after bypass, while a relatively lower percentage of
      perioperative requirement of diuretics was observed in the low frequency
      pulsatile group. A better performance to oxidative stress was seen in the low
      frequency group with higher levels of NO and lower concentration of ET-1, and
      both intergroup differences were found (P<0.01). Satisfactory clinical outcome
      was obtained on post procedure course in all groups. Conclusion: Pulsatile
      perfusion with low frequency setting in pediatric patients undergoing congenital
      cardiac surgery showed better hemodynamic profiles, potential protective effects
      on vital organs, better oxidative status and satisfactory clinical outcome.

PMID- 30233193
TI  - A preliminary evaluation of serum level of testosterone, LH, and FSH in patients
      with varicocele after varicocelectomy as a kidney-related disease.
AB  - Introduction: Varicocele is a common problem with a high prevalence in population
      with primary and secondary infertilities. The adverse effects of varicocele on
      spermatogenesis and fertility are known, but the association between clinical
      varicocele and testosterone is not clear. Hence, we decided to evaluate the serum
      levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH) in patients with varicocele after varicocelectomy. Methods: In this study,
      100 patients with varicocele were divided into two groups: hypogonadal patients
      with testosterone level <280 ng/dL and eugonadal patients with testosterone level
      >280 ng/dL. The serum levels of testosterone, FSH, and LH were measured before
      surgery and 3 months after surgery, and the results were analyzed using the SPSS
      software. P-value <0.05 was considered statistically significant. Results:
      Patients with varicocele after puberty till 50 years were divided into two
      groups: hypogonadal (testosterone <280 ng/dL) and eugonadal (testosterone >280
      ng/dL) patients who required varicocelectomy. The mean testosterone level before
      surgery in hypogonadal patients was 215.22+/-83.31 ng/dL, which reached 326.95+/
      35.125 ng/dL after surgery (P<0.0001), which was significant. There was no
      significant decrease in the mean FSH level, but there was a significant decrease
      in the mean LH level after varicocelectomy. In eugonadal group, testosterone
      level before surgery was 471.90+/-145.71 ng/dL, which reached 469.57+/-145.61
      ng/dL after surgery, which was not significant. Conclusion: In our study,
      patients who underwent varicocelectomy had improved testosterone levels, so that
      this increase was more significant in hypogonadal patients than in eugonadal
      patients. Decrease in LH and FSH levels in all patients was seen after
      varicocelectomy, which can be due to increase in testosterone levels.

PMID- 30233192
TI  - The potential of CAR T therapy for relapsed or refractory pediatric and young
      adult B-cell ALL.
AB  - Recent advancements in immunooncology have resulted in the generation of novel
      therapies such as chimeric antigen receptor (CAR) T cells, which have
      revolutionized the treatment of pediatric patients with relapsed or refractory B
      cell acute lymphoblastic leukemia. The journey of tisagenlecleucel (formerly
      CTL019) from early preclinical success to the US Food and Drug Administration
      approval is summarized in this review. Strategies that are currently being
      investigated to improve the efficacy and safety profile of CAR T-cells are also
      explored, as well as the factors contributing to the present state of patient
      access to CAR T therapy.

PMID- 30233194
TI  - Polypharmacy leads to increased prevalence of potentially inappropriate
      medication in the Indonesian geriatric population visiting primary care
      facilities.
AB  - Background: The geriatric population is particularly vulnerable to being
      prescribed potentially inappropriate medication (PIM); however, the prevalence of
      this occurrence remains poorly investigated in Indonesia. Thus in this research,
      we focused on investigating the prevalence and predictors of PIM among the
      Indonesian geriatric population in a primary health care setting. Methods: A
      retrospective observational study was conducted in 25 primary health care
      facilities in Karawang District, Indonesia. The medical prescriptions of patients
      aged >=60 years during January-December 2014 were documented, and the PIM was
      assessed based on Beers and McLeod criteria. The influence of age, sex, number of
      diseases, and polypharmacy toward PIM was assessed using a logistic regression
      model. A P-value of <0.05 defined statistical significance. Results: A total of
      3,819 subjects were included in the study. PIM was highly prevalent (52.2%) among
      the Indonesian elderly. Chlorpheniramine, mefenamic acid, ibuprofen, and
      nifedipine were the most commonly prescribed PIM. Polypharmacy (odds ratio: 1.2
      [0.6, 2.1]) was the only factor associated with the use of PIM, while sex, age,
      and multiple diseases did not show significant association. Conclusion: PIM is a
      concern in the Indonesian geriatric population. Health care professionals are
      encouraged to review the medications of their geriatric patients using updated
      safety guidelines to prevent risks associated with PIM.

PMID- 30233196
TI  - The addition of capnography to standard monitoring reduces hypoxemic events
      during gastrointestinal endoscopic sedation: a systematic review and meta
      analysis.
AB  - Background: The use of capnography monitoring devices has been shown to lower the
      rates of hypoxemia via early detection of respiratory depression, and facilitate
      more accurate titration of sedatives during procedures. The aim of the current
      meta-analysis was to compare the incidence of hypoxemia associated with standard
      monitoring alone during gastrointestinal endoscopy to that associated with
      standard monitoring with the addition of capnography. Methods: The MEDLINE,
      EMBASE, and Cochrane Central Register of Controlled Trials scientific databases
      were searched to identify relevant studies. We performed a meta-analysis of
      randomized controlled trials undertaken up to January 2018 that met our
      predefined inclusion criteria. The study outcome measures were incidence of
      hypoxemia, severe hypoxemia, apnea, the use of assisted ventilation, the use of
      supplemental oxygen, and change in vital signs. Results: We included nine trials
      assessing a total of 3,088 patients who underwent gastrointestinal procedural
      sedation. Meta-analysis of study outcome revealed that capnography significantly
      reduced the incidence of hypoxemia (odds ratio 0.61, 95% CI 0.49-0.77) and severe
      hypoxemia (odds ratio 0.53, 95% CI 0.35-0.81). However, there were no significant
      differences in other outcomes including incidence of apnea, assisted ventilation,
      supplemental oxygen, and changes in vital signs. Early procedure termination and
      patient satisfaction-related outcomes did not differ significantly in the
      capnography group and the standard monitoring group. Conclusion: This study
      indicates that capnography monitoring is an important addition with regard to the
      detection of hypoxemia during gastrointestinal procedural sedation, and should be
      considered in routine monitoring during gastrointestinal endoscopy.

PMID- 30233195
TI  - Drug-induced tubulointerstitial nephritis in a retrospective study using
      spontaneous reporting system database.
AB  - Introduction: Tubulointerstitial nephritis (TIN) is a problem in clinical
      settings because drug therapy is the cause in most cases. Patients often present
      with nonspecific symptoms, which can lead to delays in the diagnosis and
      treatment of the disease. The purpose of this study was to clarify the rank-order
      of the association of TIN with the causative drugs using a spontaneous reporting
      system database. Materials and methods: Data were extracted from the Japanese
      Adverse Drug Event Report database of the Pharmaceuticals and Medical Devices
      Agency (Japan). Based on 5,195,890 reports of all adverse reactions, we obtained
      3,088 reports of TIN caused by all drugs and calculated the reporting odds ratio
      (ROR) and 95% CI for TIN. Results: The 5 drugs with the highest RORs were
      gliclazide (ROR, 30.5; 95% CI, 17.4-53.2), tosufloxacin tosilate hydrate (ROR,
      29.5; 95% CI, 21.3-41.0), piperacillin-tazobactam (ROR, 24.3; 95% CI, 19.4-30.5),
      cefteram pivoxil (ROR, 23.5; 95% CI, 12.5-44.2), and mefenamic acid (ROR, 22.5;
      95% CI, 13.4-37.7). No sex-related difference was observed in drug-induced TIN.
      Most of the reports about TIN onset following the administration of culprit drugs
      were recorded within 12 weeks. Conclusion: Based on the results, a comprehensive
      study using a pharmacovigilance database enabled us to identify the dugs that
      most frequently induced TIN, so these drugs should be used carefully in clinical
      practice to avoid TIN.

PMID- 30233197
TI  - Impacts of age and gender at the risk of underlying medical conditions and death
      in patients with avian influenza A (H7N9): a meta-analysis study.
AB  - Objective: The objective of our study was to conduct a series of analyses that
      examined the impacts of age and gender at the risk of underlying medical
      conditions (UMCs) and death in patients with influenza A (H7N9). Methods: We
      began by searching for potentially relevant articles in English or Chinese before
      February 28, 2018. Additionally, we reviewed our own files and reference lists of
      articles identified by this search. Results: The association between death and
      UMCs was significant in H7N9 patients, with an OR of 1.49 (95% CI: 1.24-1.78).
      Subgroup analyses showed that having two or more UMCs of any type (OR: 2.24;
      P=0.044), chronic respiratory diseases (OR: 1.81; P=0.032), and chronic
      cardiovascular disease (OR: 1.63; P=0.013) had an association with increased
      fatality in H7N9 patients. Age (60 years or older) [adjusted OR (AOR): 1.86;
      P=0.032] and gender (male: AOR: 1.68, P=0.006; female: AOR: 1.88, P=0.044) were
      significantly associated with death in H7N9 patients with UMCs compared to H7N9
      patients without any UMC. Stratification analyses found statistically significant
      increased death in H7N9 patients with UMCs who were 60 years of age and older
      (AOR: 2.72; P<0.001) and gender (male; AOR=1.64; P=0.033), compared to H7N9
      patients without these respective conditions. Conclusion: Impacts of age are
      substantial and significant at the risk of UMCs and death in H7N9 patients. This
      analysis did not find a significant difference in gender comparisons. Efforts
      should particularly focus on reducing fatality rates in patients with combined
      risks from UMCs and other significant impact factor such as age (60 years or
      older).

PMID- 30233198
TI  - Th17/Treg homeostasis, but not Th1/Th2 homeostasis, is implicated in exacerbation
      of human bronchial asthma.
AB  - Background: Th17 and regulatory T cell (Treg) play crucial roles in the
      pathogenesis of asthma. However, the association between Th17/Treg homeostasis
      and asthma exacerbation remains unclear. Patients and methods: To investigate the
      role of Th17/Treg bias in asthma exacerbation, 49 asthma patients were enrolled
      in the current study, of whom 31 had acute asthma exacerbation (exacerbation
      group) and 18 did not (non-exacerbation group). Meanwhile, 17 healthy subjects
      were recruited as normal controls (control group). By measuring interleukin (IL)
      4, IL-13, interferon (IFN)-gamma, IL-10, and IL-17A levels in plasma using enzyme
      linked immunosorbent assay (ELISA) and determining the mRNA expression of T-bet,
      GATA-3, forkhead/winged helix transcription factor (Foxp3), and receptor-related
      orphan receptor gammat (RORgammat) in peripheral blood mononuclear cells (PBMCs)
      by quantitative real-time PCR. Results: We found that IL-17A/IL-10 and
      RORgammat/Foxp3 ratios were significantly increased in the exacerbation group
      compared with that in the non-exacerbation group, while IL-4/IFN-gamma and GATA
      3/T-bet ratios remained unchanged. Moreover, IL-17A/IL-10 and RORgammat/Foxp3
      ratios, but not IL-4/IFN-gamma or GATA-3/T-bet ratios, negatively correlated with
      forced expiratory volume in the first second (FEV1)/FEV1pred and Asthma Control
      Test Questionnaire (ACT) scores in both exacerbation group and non-exacerbation
      group. In contrast, the IL-4/IFN-gamma ratio was negatively correlated with
      FEV1/FEV1pred and ACT scores only in the non-exacerbation group but not in the
      exacerbation group, while the ratio of GATA-3/T-bet was correlated with neither
      FEV1/FEV1pred nor ACT scores in both groups with asthma. Conclusion: Our results
      suggest that the homeostasis of the Treg and Th17 cells is broken in asthma
      exacerbation and correlates with asthma severity and disease control status. The
      outcome has significant implication in understanding the progression of asthma
      and providing helpful information for physicians in the diagnosis and treatment
      of asthma patients.

PMID- 30233200
TI  - A life put on hold: adolescents' experiences of having an eating disorder in
      relation to social contexts outside the family.
AB  - Background: As suffering from an eating disorder often entails restrictions on a
      person's everyday life, one can imagine that it is an important aspect of
      recovery to help young people learn to balance stressful demands and expectations
      in areas like the school environment and spare-time activities that include
      different forms of interpersonal relationships. Purpose: The aim of the present
      study was to investigate how adolescents with experience from a restrictive
      eating disorder describe their illness and their time in treatment in relation to
      social contexts outside the family. Patients and methods: This qualitative study
      is based on narratives of 15 adolescents with experience from outpatient
      treatment for eating disorders with a predominately restrictive symptomatology,
      recruited in collaboration with four specialized eating-disorder units. Data were
      explored through inductive thematic analysis. Results: The adolescents'
      descriptions of their illness in relation to their social contexts outside the
      family follow a clear timeline that includes narratives about when and how the
      problem arose, time in treatment, and the process that led to recovery. Three
      main themes were found: 1) the problems emerging in everyday life (outside the
      family); 2) a life put on hold and 3) creating a new life context. Conclusion:
      Young people with eating disorders need to learn how to balance demands and
      stressful situations in life, and to grasp the confusion that often preceded
      their illness. How recovery progresses, and how the young people experience their
      life contexts after recovery, depends largely on the magnitude and quality of
      peer support and on how school and sports activities affect and are affected by
      the eating disorder.

PMID- 30233199
TI  - Low nitric oxide level is implicated in sickle cell disease and its complications
      in Ghana.
AB  - Background: Nitric oxide (NO) plays a fundamental role in maintaining normal
      vasomotor tone. Recent clinical and experimental data suggest that NO may play a
      role in the pathogenesis and therapy of sickle cell disease (SCD). The aim of
      this study was to determine NO metabolites (NOx) in SCD patients at steady state
      and in vaso-occlusive crisis (VOC), as well as those with hemolytic clinical sub
      phenotype that includes leg ulcers and priapism. Methodology: This was a case
      control cross-sectional study conducted on a total of 694 subjects including 148
      comparison group HbAA, 208 HbSS SCD patients in steady state, 82 HbSC SCD
      patients in steady state, 156 HbSS SCD patients in VOC, 34 HbSC SCD patients in
      VOC, 34 HbSS SCD patients in post VOC, 21 HbSS SCD patients with leg ulcer and 11
      HbSS SCD patients with priapism, with age ranging from 15 to 65 years. Laboratory
      diagnosis of SCD was done at the Sickle Cell Clinic of the Korle-Bu Teaching
      Hospital. Plasma nitric oxide metabolites were measured using Griess reagent
      system by ELISA method. Results: Mean NOx of 59.66+/-0.75 uMol/L in the
      comparison group was significantly different from those in steady state (P=0.02).
      During VOC, there was a significant reduction in mean NOx levels to 6.08+/-0.81
      uMol/L (P<0.001). Mean NOx levels were however, significantly higher (50.97+/
      1.68 uMol/L) (P<0.001) in the immediate postcrisis period. The mean NOx levels in
      the leg ulcer (21.70+/-1.18 uMol/L) (P<0.001) and priapism (28.97+/-1.27 uMol/L)
      (P<0.001) patients were significantly low as compared to the SCD patients in the
      steady state and comparison group. Conclusion: This study presents the first
      report on plasma NOx levels in SCD complication in Ghanaian SCD patients and
      confirms reduced plasma NOx levels in SCD patients in general.

PMID- 30233201
TI  - Evaluation of maternal and newborn health services in Jordan.
AB  - Objectives: This study aimed to assess the maternal and newborn services in
      Jordanian hospitals to provide policymakers, health professionals, and
      researchers with a clear picture about the current status of maternal and newborn
      health services. Methods: A total of 32 main hospitals that provide maternity
      services in Jordan were assessed. The study involved direct observations of these
      hospitals and interviews with basic health and hospital staff, with the purpose
      of assessing and evaluating the availability of various services for mothers and
      newborns, availability of resources, equipment and supplies, documentation and
      staff training, and provision of the health care services. Results: Some
      hospitals had shortages of obstetricians and gynecologists, pediatricians,
      neonatologists, and midwives/nurses. Antenatal care was not provided
      systematically in many hospitals across the country. A lack of necessary
      equipment, drugs, and supplies was evident in some hospitals. Admission
      departments of some hospitals had insufficient supplies. The operation theaters
      in many hospitals lacked a variety of necessary equipment including some basic
      items such as thermometers and some advanced items such as resuscitation sets for
      babies. Only two-thirds of all delivery rooms in the selected hospitals had
      radiant heaters and obstetrical stethoscopes available. A significant lack of
      neonatal ICU equipment was found such as incubators, resuscitation tables,
      continuous positive airway pressure, O2 oximeters, and phototherapy. Conclusion:
      The findings revealed an overall satisfactory quality of maternal and newborn
      care and services, however, some deficiencies existed. The findings are expected
      to aid policymakers, health professionals, and researchers to recognize the gaps
      in the processes, supplies, and quality of care related to the provided services
      at maternal facilities and help them to design and implement evidence-based
      health programs in order to provide effective health services and promote the
      health of mothers and newborns.

PMID- 30233203
TI  - MicroRNA 628 suppresses migration and invasion of breast cancer stem cells
      through targeting SOS1.
AB  - Purpose: The purpose of this study is to evaluate the effects of miR-628 on
      migration and invasion of breast cancer stem cells (CSCs), which are essential
      for tumor recurrence and metastasis. Materials and methods: Quantitative reverse
      transcription-polymerase chain reaction was used to determine the expression of
      microRNAs and mRNAs. A subpopulation of CD44+/CD24- breast CSCs were sorted by
      flow cytometry. Transwell assays were used to evaluate cell migration and
      invasion. Luciferase reporter assays were performed to verify whether miR-628
      targeted SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1). pcDNA3.1(+)
      SOS1 was constructed for overexpressing SOS1 after transfection. Results:
      Compared with primary breast cancer cells, bone metastatic breast cancer cells
      showed significant downregulation of miR-628. The CD44+/CD24- breast CSC
      subpopulations in MDA-MB-231 and MCF-7 cell lines were analyzed and sorted.
      Transfection with an miR-628 mimic significantly suppressed the migration and
      invasion of these breast CSCs by targeting SOS1, which plays an essential role in
      epithelial-to-mesenchymal transition. Overexpression of SOS1 rescued miR-628
      mediated migration and invasion by upregulating Snail and vimentin, and
      downregulating E-cadherin. Conclusion: miR-628 suppressed migration and invasion
      of breast CSCs of MDA-MB-231 and MCF-7 cells by directly targeting SOS1.
      Enhancement of miR-628 expression might be an effective strategy for managing
      breast cancer metastasis.

PMID- 30233202
TI  - Expression profiles of long noncoding RNAs in lung adenocarcinoma.
AB  - Purpose: This study aimed to analyze expression profiles of long noncoding RNAs
      (lncRNAs) in lung adenocarcinoma. Methods: lncRNA microarray technology was
      employed to detect lncRNA profiles of 3 pairs of lung adenocarcinoma tissues and
      adjacent tissues. Results: We found 134 upregulated lncRNAs and 460 downregulated
      lncRNAs in lung adenocarcinoma tissues compared to adjacent tissues. Among them,
      LINC00152, LINC00691, and LINC00578 showed the most significant changes of
      upregulation, while LINC00668, LINC00710, and LINC00607 showed the most
      significant changes of downregulation. Fluorescent quantitative polymerase chain
      reaction (PCR) analysis of tissue samples from an additional 90 patients with
      lung adenocarcinoma showed significantly increased levels of LINC00152,
      LINC00691, and LINC00578 and decreased levels of LINC00668, LINC00710, and
      LINC00607 in lung adenocarcinoma tissues. In addition, LINC00578 was closely
      associated with the existence of metastasis of lung adenocarcinoma, but the other
      5 lncRNAs showed no significant correlation with clinicopathologic
      characteristics such as age, gender, tumor stage, and the existence of
      metastasis. Further follow-up study showed that LINC00578 expression was closely
      associated with the survival of patients with lung adenocarcinoma. Conclusion: We
      revealed the expression profiles of lncRNAs in lung adenocarcinoma and identified
      LINC00578 as a promising biomarker and therapeutic target for lung
      adenocarcinoma.

PMID- 30233182
TI  - Design of a transdermal formulation containing raloxifene nanoparticles for
      osteoporosis treatment.
AB  - Purpose: In the clinical setting, raloxifene, a second-generation selective
      estrogen receptor modulator, is administered orally; however, the bioavailability
      (BA) is only 2% because of its poor solubility in aqueous fluids and its
      extensive first-pass metabolism. Therefore, it is expected that the development
      of a transdermally delivered formulation may reduce the necessary dose without
      compromising its therapeutic efficacy. In this study, we designed transdermal
      formulations containing raloxifene nanoparticles and evaluated their usefulness
      for osteoporosis therapy. Methods: Raloxifene was crushed with methylcellulose by
      the bead mill method, and the milled raloxifene was gelled with or without
      menthol (a permeation enhancer) by Carbopol(r) 934 (without menthol, Ral-NPs;
      with menthol, mRal-NPs). The drug release and transdermal penetration were
      measured using a Franz diffusion cell, and the therapeutic evaluation of
      osteoporosis was determined in an ovariectomized rat model. Results: The mean
      particle size of raloxifene in the transdermal formulation (Ral-NPs) was 173.7
      nm. Although the raloxifene released from Ral-NPs remained in the nanoparticle
      state, the skin penetration of raloxifene nanoparticles was prevented by the
      stratum corneum in rat. On the other hand, inclusion of menthol in the
      formulation attenuated the barrier function of the stratum corneum and permitted
      the penetration of raloxifene nanoparticles through the skin. Moreover,
      macropinocytosis relates to the skin penetration of the formulation including
      menthol (mRal-NPs), since penetration was inhibited by treatment with 2 uM
      rottlerin, a macropinocytosis inhibitor. In addition, the application of 0.3%
      mRal-NPs (once a day) attenuated the decreases in calcium level and stiffness of
      the bones of ovariectomized rat. Conclusion: We prepared raloxifene solid
      nanoparticles by a bead mill method and designed a novel transdermal formulation
      containing nanoparticles and permeation enhancers. These trans-dermal
      formulations overcome the barrier properties of the skin and show high drug
      penetration through the transdermal route (BA 8.5%). In addition, we found that
      raloxifene transdermal formulations are useful for the treatment of osteoporosis
      in ovariectomized rat.

PMID- 30233204
TI  - Natural borneol is a novel chemosensitizer that enhances temozolomide-induced
      anticancer efficiency against human glioma by triggering mitochondrial
      dysfunction and reactive oxide species-mediated oxidative damage.
AB  - Background: Temozolomide (TMZ)-based chemotherapy represents an effective way for
      treating human glioma. However, its clinical application is limited because of
      its side effects and resistance to standard chemotherapy. Hence, the search for
      novel chemosensitizers to augment their anticancer efficiency has attracted much
      attention. Natural borneol (NB) has been identified as a potential
      chemosensitizer in treating human cancers. However, the synergistic effect and
      mechanism of NB and TMZ in human glioma have not been investigated yet. Materials
      and methods: U251 human glioma cells were cultured, and the cytotoxicity and
      apoptosis of NB and/or TMZ were examined by MTT assay, flow cytometric analysis
      and Western blot. Nude mice tumor model was also employed to evaluate the in vivo
      anticancer effect and mechanism. Results: The results showed that the combined
      treatment of NB and TMZ more effectively inhibited human glioma growth via
      triggering mitochondria-mediated apoptosis in vitro, accompanied by the caspase
      activation. Combined treatment of NB and TMZ also caused mitochondrial
      dysfunction through disturbing Bcl-2 family expression. Further investigation
      revealed that NB enhanced TMZ-induced DNA damage through inducing reactive oxide
      species (ROS) overproduction. Moreover, glioma tumor xenograft growth in vivo was
      more effectively inhibited by the combined treatment with NB and TMZ through
      triggering apoptosis and anti-angiogenesis. Conclusion: Taken together, our
      findings validated that the strategy of using NB and TMZ could be a highly
      efficient way to achieve anticancer synergism.

PMID- 30233205
TI  - Mifepristone inhibits proliferation, migration and invasion of HUUA cells and
      promotes its apoptosis by regulation of FAK and PI3K/AKT signaling pathway.
AB  - Purpose: The aim was to investigate mifepristone effects on endometrial carcinoma
      and the related mechanism. Methods: HHUA cells were treated with DMEM containing
      different concentrations of mifepristone. HHUA cells treated with 100 MUmol/L
      mifepristone were named the Mifepristone group. HHUA cells co-transfected with
      pcDNA3.1-PI3K and pcDNA3.1-AKT overexpression vectors were treated with 100
      MUmol/L mifepristone and named the Mifepristone + PI3K/AKT group. mRNA expression
      was detected by quantitative reverse transcription PCR. Protein expression was
      performed by Western blot. Cell proliferation was conducted by MTT assay. Wound
      healing assay was conducted. Transwell was used to detect cells migration and
      invasion. Apoptosis detection was performed by flow cytometry. Results:
      Mifepristone inhibited HHUA cells proliferation in a dose-dependent manner.
      Compared with HHUA cells treated with 0 MUmol/L mifepristone, HHUA cells treated
      by 50-100 MUmol/L mifepristone had a lower wound-healing rate, a greater number
      of migrating and invasive cells (P<0.01), as well as a higher percentage of
      apoptotic cells and Caspase-3 expression (P<0.01). When HHUA cells were treated
      with 50-100 MUmol/L of mifepristone, FAK, p-FAK, p-PI3K and p-AKT relative
      expression was all significantly lower than HHUA cells treated with 0 MUmol/L of
      mifepristone (P<0.01). Compared with the Mifepristone group, HHUA cells of the
      Mifepristone + PI3K/AKT group had a lower cell growth inhibition rate and
      percentage of apoptotic cells (P<0.01). Conclusion: Mifepristone inhibited HUUA
      cells proliferation, migration and invasion and promoted its apoptosis by
      regulation of FAK and PI3K/AKT signaling pathway.

PMID- 30233206
TI  - Prognostic value of CD44v6 expression in breast cancer: a meta-analysis.
AB  - Purpose: The prognostic value and clinical significance of CD44 variant isoform
      v6 (CD44v6) in breast cancer remains controversial. Our study aimed to generalize
      the correlation between CD44v6 expression and clinicopathological features and
      prognosis in breast cancer by using a meta-analysis. Methods: We performed a
      comprehensive search of relevant literature from PubMed, Cochrane Database, and
      EMBASE database that were published before January 2018. The pooled ORs and HRs
      with 95% CIs were used to estimate the effects. Results: Thirteen articles
      comprising 1,458 patients were included for analysis. The results revealed that
      CD44v6 expression was associated with histological grade (overall: OR=1.56, 95%
      CI [1.06, 2.29], P=0.023; Asian: OR=1.78, 95% CI [1.12, 2.85], P=0.016) and lymph
      node metastasis (overall: OR=1.96, 95% CI [1.01, 3.78], P=0.046; Asian: OR=2.11,
      95% CI [1.00, 4.44], P=0.049). CD44v6 expression was significantly associated
      with poor prognosis in patients with breast cancer (overall survival: overall:
      HR=1.55, 95% CI [1.09, 2.22], P=0.015; Asian: HR=2.22, 95% CI [1.34, 3.68],
      P=0.002). Conclusion: Our meta-analysis demonstrates that CD44v6 is significantly
      associated with poor prognosis, histological grade, and lymph node metastasis in
      breast cancer patients, especially among Asian patients.

PMID- 30233207
TI  - Clinical benefit of fulvestrant monotherapy in the multimodal treatment of
      hormone receptor and HER2 positive advanced breast cancer: a case series.
AB  - Fulvestrant is a pure estrogen receptor (ER) antagonist approved for the
      treatment of metastatic ER positive breast cancer in postmenopausal women with
      disease progression following antiestrogen therapy. The clinical results of
      fulvestrant demonstrated encouraging activity in tumors in spite of HER2
      positivity, but data about its use after progression on anti-HER2 agents are
      limited. Partial responses and durations of response of 12, 25, and 38 months in
      three cases with multiple metastases of ER positive and HER2 positive breast
      cancer were observed; all patients had been treated with 1-4 regimens of an anti
      HER2 agent in combination with chemotherapy or an aromatase inhibitor before the
      initiation of fulvestrant. Fulvestrant is a valuable option with limited toxicity
      and durable response in metastatic HER2 and ER positive breast cancer after
      progression on anti-HER2 agents as well. Therapeutic benefit even in extensive
      skin metastases and (irradiated) brain metastases may be expected. Further
      investigations are warranted to establish where it fits into the multimodal
      management of ER and HER positive breast cancer.

PMID- 30233209
TI  - Absence of AIF1L contributes to cell migration and a poor prognosis of breast
      cancer.
AB  - Background: Breast cancer is the most common fatal cancer in women worldwide.
      Previous studies have demonstrated that allograft inflammatory factor 1 like
      (AIF1L) plays a key role in mammary tumorigenesis, although the mechanism
      involved remains unclear. Purpose: The purpose of this study was to assess the
      clinicopathological and prognostic significance of AIF1L expression levels and
      biological function in breast cancer. Patients and methods: We used
      immunohistochemistry to detect the expression of AIF1L in breast cancer. We also
      analyzed the expression of AIF1L in breast cancer using the Cancer Genome Atlas
      (TCGA) cohort and the Cancer Cell Line Encyclopedia (CCLE). Furthermore, both in
      vitro assays were used to determine the effect of AIF1L on malignant behavior in
      breast cancer cells. Results: We detected AIF1L expression in tissue microarrays
      through immunohistochemistry and found that protein expression was significantly
      lower in BC tissues (28.6%, 82/287) compared to tumor-adjacent tissues (58.3%,
      28/48) (P=0.007). Kaplan-Meier survival analysis revealed that disease-specific
      survival in BC patients with low AIF1L protein expression was significantly
      poorer compared to normal controls (P=0.040). In the TCGA cohort, the AIF1L gene
      was downregulated and hypermethylated in tumor samples compared to normal
      controls. Bioinformatics analysis using CCLE predicted potential biological
      functions of AIF1L related to tight junctions, cell junctions and focal adhesion.
      Ectopic expression of AIF1L suppressed MDA-MB-231 migration and invasion. Further
      evidence confirmed that AIF1L overexpression suppressed cell spreading, altered
      cell shape and decreased protrusion formation, which was correlated with
      decreased focal adhesion kinase (FAK) and RhoA expression. Conclusion: These
      findings suggest that AIF1L is a potential prognostic biomarker that plays a
      vital role in regulating the cytoskeleton in breast cancer.

PMID- 30233208
TI  - Altered fractionation radiotherapy with or without chemotherapy in the treatment
      of head and neck cancer: a network meta-analysis.
AB  - Objectives: A Bayesian network meta-analysis (NMA) was conducted in patients with
      head and neck cancers (HNCs) to estimate the efficacy and safety of treatment
      with conventional fractionation radiotherapy (CF), conventional fractionation
      chemoradiotherapy (CF_CRT), hyperfractionated radiotherapy (HF),
      hyperfractionated chemoradiotherapy (HF_CRT), accelerated fractionation
      radiotherapy, accelerated fractionation chemoradiotherapy, accelerated
      hyperfractionated radiotherapy (HART) or accelerated hyperfractionated
      chemoradiotherapy (HACRT) to identify superior treatments to aid in clinical
      decisions. Methods: PubMed, EMBASE and the Cochrane Central Register of
      Controlled Trials (CENTRAL) were searched for potentially eligible randomized
      controlled trials up to December 2016. Overall survival (OS), disease-free
      survival (DFS) and locoregional control (LRC) were considered efficacy outcomes,
      whereas acute toxicity and late toxicity on skin and mucosa were considered
      safety outcomes. The surface under the cumulative ranking curve (SUCRA) was
      calculated to rank each treatment in each index. Results: Data from 72 trials
      with 21,868 participants were included in the analysis. Concerning OS, all
      treatments were associated with a significant advantage compared to CF alone,
      with HR effect sizes ranging from 0.64 to 0.83, and HACRT was significantly more
      effective than all the other treatments. The network comparisons of both HACRT vs
      HART and HF_CRT vs HF demonstrated a higher OS benefit, with an HR of 0.78 (95%
      credible interval [CrI]: 0.64-0.95) and 0.78 (95% CrI: 0.61-0.99), respectively.
      The results of SUCRA indicated that HACRT had the best ranking for OS and LRC,
      HF_CRT for DFS, HART for acute and late skin toxicity, CF_CRT for acute mucosal
      toxicity and HF_CRT for late mucosal toxicity. Conclusion: The NMA results
      support the notion that HACRT is the preferable treatment modality for HNCs
      because it has better rankings in all three efficacy indexes, although it does
      present a high risk of acute mucosal toxicity.

PMID- 30233210
TI  - Suppression of c-MET overcomes erlotinib resistance in tongue cancer cells.
AB  - Background: Erlotinib is a commonly used molecular-targeted drug for the
      treatment of tongue cancer. However, the development of acquired resistance to
      erlotinib hampers its therapeutic use. Materials and methods: To analyze the
      erlotinib resistance, long-term and short term survival assay were used to
      compare the resistance between parental and resistant tongue cancer cells. Flow
      cytometry, Hochest staining and western blot were used to analyze the apoptosis
      among the cells. Moreover, Transwell and wound healing assay were used to compare
      the invasion ability of the cells. To deeply explore the drug resistance in vivo,
      orthotopic tumor studies were applied. Finally, to explain the mechanism of c-met
      in erlotinib resistance, shRNA against c-met was used to down-regulate the
      expression of c-met. And SU11274 also used in orthotopic model. Results: We
      established erlotinib-resistant human tongue cancer cell line by chronic exposure
      of TCA-8113 cells to increasing concentrations of erlotinib and determined the
      role of c-MET and EGFR in the development of acquired resistance. We found a
      significant increase in the phosphorylation of c-MET and an obvious decrease of
      the phosphorylation of EGFR in erlotinib-resistant cells. Our results also
      revealed that inhibition of c-MET alone with SU11274 exerted an inhibitory effect
      on the proliferation of erlotinib-resistant cells in the short term; however, it
      failed to sustain the inhibitory effect in the long term. Simultaneous inhibition
      of c-MET and EGFR significantly inhibited the proliferation of erlotinib
      resistant cells in both a short and long period. Furthermore, we explored the
      underlying mechanism and found that treatment of erlotinib-resistant cells with
      SU11274 or shRNA against c-MET induced the phosphorylation of EGFR. Moreover, our
      results demonstrated that simultaneous inhibition of c-MET and EGFR significantly
      inhibited the migration and invasion of erlotinib-resistant cells. Conclusion:
      Taken together, our results suggested that c-MET is involved in acquired drug
      resistance to erlotinib and that cotargeting of EGFR and c-MET could overcome
      acquired resistance to erlotinib and inhibit the invasion and metastasis of
      erlotinib-resistant cells.

PMID- 30233212
TI  - Erratum: An evaluation of the clinical diagnostic value of contrast-enhanced
      ultrasound combined with contrast-enhanced computed tomography in space-occupying
      lesions of the kidney [Corrigendum].
AB  - [This corrects the article on p. 3493 in vol. 10, PMID: 28761358.].

PMID- 30233211
TI  - Comparison of efficacy and toxicity between nedaplatin and cisplatin in treating
      malignant pleural effusion.
AB  - Objective: To evaluate the efficacy and safety of nedaplatin versus cisplatin in
      treating malignant pleural effusion (MPE) caused by cancers. Methods: The
      clinical data of 219 MPE patients treated from January 2013 to December 2016 were
      retrospectively reviewed. Intrapleural infusion with nedaplatin 80 mg/m2 (n=110)
      or with cisplatin 40 mg/m2 (n=109) were used as the treatment. Results: There was
      no significant difference in the overall response rate between the nedaplatin
      group (62.73%) and the cisplatin group (54.13%) (P=0.154). The nedaplatin group
      had significantly lower rates of gastrointestinal side effects and significantly
      less incidence of increased serum creatinine levels in comparison with the
      cisplatin group. The overall rate of toxicity in the nedaplatin group (40.00%)
      was significantly lower than in the cisplatin group (78.90%) (P?0.001).
      Conclusion: The efficacy of pleural perfusion with nedaplatin is noninferior to
      cisplatin in treating malignancy-induced MPE. Nedaplatin is associated with less
      toxicity in comparison with cisplatin.

PMID- 30233215
TI  - Effective treatment of pulmonary adenocarcinoma harboring triple EGFR mutations
      of L858R, T790M, and cis-C797S by osimertinib, bevacizumab, and brigatinib
      combination therapy: a case report.
AB  - Osimertinib is commonly used in pulmonary adenocarcinoma patients who are
      resistant to first-generation epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors and carry the T790M mutation. However, the use of osimertinib
      may result in the development of further resistance, most commonly via the cis
      C797S mutation. Herein, we report a case of a lung cancer patient harboring
      triple EGFR mutations of L858R, T790M, and cis-C797S who was treated with a
      combination of osimertinib, bevacizumab, and brigatinib. The above 3 mutations
      were detected by circulating tumor DNA analysis after osimertinib treatment.
      Subsequently, the patient received combination therapy of osimertinib and
      bevacizumab; the partial relief obtained was negated by later disease
      progression. The regimen was then changed to osimertinib, bevacizumab, and
      brigatinib combination therapy. Partial remission was observed, and a significant
      reduction in EGFR mutations was detected. This case represents the first evidence
      that 1) bevacizumab combined with osimertinib can significantly relieve tumor
      growth and respiratory symptoms in non-small-cell lung cancer patients with
      osimertinib resistance and 2) the clinical use of osimertinib, bevacizumab, and
      brigatinib is effective as combination therapy for pulmonary adenocarcinoma in
      the presence of triple EGFR mutations of L858R, T790M, and cis-C797S. These
      combination therapies may provide potential novel treatment options for pulmonary
      adenocarcinoma patients.

PMID- 30233213
TI  - Prognostic significance of NANOG expression in solid tumors: a meta-analysis.
AB  - Purpose: NANOG is a tumor marker and indicates poor prognosis in various
      neoplasms; however, the evidence is controversial. This meta-analysis
      investigated the association of NANOG expression and clinicopathological
      features, and it impact on survival of patients with malignant tumors. Methods:
      Studies published through May 31, 2018 were retrieved from PubMed, Web of
      Science, Embase, and the China National Knowledge Infrastructure. Two researchers
      independently screened the content and quality of studies and extracted data.
      Correlations of NANOG expression, clinicopathological variables, and survival
      were analyzed and the combined odds ratios (ORs) and hazard ratios (HRs) with 95%
      confidence intervals (95% CIs) were calculated. Results: Thirty-three articles
      including 35 data sets of 3,959 patients were analyzed. Overall, elevated NANOG
      expression was associated with poor overall survival (HR = 2.19; 95% CI: 1.87
      2.58, P<0.001) and poor disease-free survival (HR = 2.21, 95% CI: 1.54-3.18,
      P<0.001). Subgroup analysis found that NANOG expression was associated with worse
      overall survival in non-small cell lung (HR = 1.87; 95% CI: 1.26-2.76, P =
      0.002), head and neck (HR = 2.29; 95% CI: 1.75-3.02, P<0.001), and digestive
      system (HR = 2.38; 95% CI: 1.95-2.91, P<0.001) cancers. Moreover, we found that
      high NANOG expression was associated with poor tumor differentiation (OR = 2.63;
      95% CI: 1.59-4.55, P = 0.001), lymph node metastasis (OR = 2.59; 95% CI: 1.50
      4.47, P = 0.001), advanced TNM stage (OR = 2.22; 95% CI: 1.42-3.45, P<0.001), and
      T stage (OR = 0.44; 95% CI: 0.20-0.93, P = 0.031). Conclusion: The evidence
      supports NANOG as a tumor biomarker to guide clinical management and indicate
      prognosis. Additional studies are needed to further validate these results.

PMID- 30233214
TI  - Nomograms for predicting long-term overall survival and disease-specific survival
      of patients with clear cell renal cell carcinoma.
AB  - Objectives: The aim of this study was to establish comprehensive and practical
      nomograms, based on significant clinicopathological parameters, for predicting
      the overall survival (OS) and the disease-specific survival (DSS) of patients
      with clear cell renal cell carcinoma (ccRCC). Patients and methods: The data of
      35,151 ccRCC patients, diagnosed between 2004 and 2014, were obtained from the
      database of the Surveillance, Epidemiology, and End Results (SEER) program. The
      Kaplan-Meier method and Cox proportional hazards regression model were used to
      evaluate the prognostic effects of multiple clinicopathological variables on
      survival. Based on Cox models, a nomogram was constructed to predict the
      probabilities of OS and DSS for an individual patient. The predictive performance
      of nomograms was evaluated using the concordance index (C-index) and calibration
      curves. Results: According to univariate and multivariate analyses, age at
      diagnosis, sex, race, marital status, surgical approach, tumor node metastasis
      (TNM) stage, and Fuhrman grade significantly correlated with the survival
      outcomes. These characteristics were used to establish nomograms. The nomograms
      showed good accuracy in predicting 3-, 5-, and 10-year OS and DSS, with a C-index
      of 0.79 (95% CI, 0.79-0.80) for OS and 0.87 (95% CI, 0.86-0.88) for DSS. All
      calibration curves revealed excellent consistency between predicted and actual
      survival. Conclusion: Nomograms were developed to predict death from ccRCC
      treated with nephrectomy. These new prognostic tools could aid in improving the
      predictive accuracy of survival outcomes, thus leading to reasonable
      individualized treatment.

PMID- 30233216
TI  - Negative correlation of cytoplasm TIMP3 with miR-222 indicates a good prognosis
      for NSCLC.
AB  - Background: The aim of this study was to observe the expression of microRNA-222
      (miR-222) and matrix metalloproteinase inhibitor 3 (TIMP3) in non-small cell lung
      cancer (NSCLC) and discuss their significance. Methods: A total of 230 patients
      with NSCLC were enrolled in the observation group during the operation. Ninety
      eight normal adjacent tissues were used as the control group. Two groups of miR
      222 and TIMP3 were detected by in situ hybridization and immunohistochemistry.
      The distribution of miR-222 and TIMP3 in A549/H358/PC9 cells was observed by
      immunofluorescence. Chi-squared and Spearman correlation tests were used to
      analyze the relationship among miR-222, TIMP3 expression, and clinicopathological
      parameters of NSCLC. Kaplan-Meier and Cox proportional hazards regression were
      used to analyze the prognostic impact of miR-222 and TIMP3. Results:
      Immunohistochemistry showed that the expression of miR-222 in lung cancer tissue
      was significantly higher, but TIMP3 was lower than that in normal lung tissue (P
      = 0.0001 for the former and P = 0.0002 for the latter). Meanwhile, miR-222 and
      TIMP3 were mainly distributed in the cytoplasm. Among them, cTIMP3 accounted for
      70.29% (72/101), cmiR-222 for 59.35% (92/155), 14.85% for nTIMP3 (15/101), and
      18.06% for nmiR-222 (28/155). There was a significant difference in distribution
      (both P < 0.0001). The expression of miR-222 and TIMP3 were negatively correlated
      in lung cancer tissues (r = -0.43, P = 0.0219). With the progression of clinical
      stage, the positive intensity of cTIMP3 showed a decreasing trend, while the cmiR
      222 showed a reverse trend (the former P = 0.0024 and the latter P < 0.0001). In
      the Kaplan-Meier prognostic analysis, we found that the high expression of cTIMP3
      could predict a better prognosis (P = 0.0040), whereas cmiR-222 was the opposite
      (P = 0.0016). Multivariate analysis shows that both can be used as independent
      factors. Conclusion: TIMP3 expression in lung cancer is relatively low and has a
      negative correlation with lung cancer staging and prognosis, suggesting that it
      may play a defensive function in the development of lung cancer, while miR-222
      has the opposite effect, and the expression of both proteins is negatively
      correlated, suggesting that in lung cancer progresses, both proteins may play
      some role together.

PMID- 30233217
TI  - CXCR2 is a novel cancer stem-like cell marker for triple-negative breast cancer.
AB  - Background: Breast cancer is the leading cause of mortality from cancer in women
      worldwide, and cancer stem-like cell (CSC) is responsible for failure treatment
      of breast cancer. It plays an important role in resistant disease and metastasis.
      CD44/CD24 and ALDH are well-accepted protein markers of breast CSC, and it was
      reported that distinct subtypes of breast CSC were identified by the 2 markers.
      It is possible that there are various kinds of breast CSC which could be
      identified by different markers, and CSC markers utilized at present are not
      enough to fully understand breast CSC. Finding out more novel CSC markers is
      necessary. CXCR2 is involved in breast cancer metastasis, treatment resistance,
      and recurrence and has positive cross-talk with known breast CSC protein markers.
      It can be concluded that CXCR2 is related to breast CSC, and further study is in
      need. Results: In this study, we assessed expression of CXCR2 with
      immunohistochemistry in breast cancer tissues from 37 patients and discovered
      that level of CXCR2 was significantly lower in triple-negative breast cancer
      (TNBC) compared with non-TNBC. CXCR2 expression decreased in estrogen receptor
      negative or HER2-negative breast cancer, but not progesterone receptor-negative
      counterparts. By immunofluorescence, we observed high coexpression rate of CXCR2
      and CSC-related proteins, including NANOG and SOX2. To prove our speculation that
      CXCR2 was a novel CSC marker for TNBC, we used 4T1 cell, which is a TNBC cell
      line, to analyze CXCR2-positive subpopulations and observed that CXCR2-positive
      4T1 cells showed characteristics of CSC, including resistance to cisplatinum,
      radiation, and hypoxia, low proportion (around 1%), much more tumor xenografts,
      tumor spherule formation, and higher levels of CSC-related mRNA compared with
      CXCR2-negative cells. Conclusion: CXCR2 is an acceptable and newly discovered CSC
      marker for only TNBC.

PMID- 30233218
TI  - Sirt1 protects neural stem cells from apoptosis by decreasing acetylation of
      histone 3K9.
AB  - Objective: To explore the role and mechanism of Sirt1 in protecting neural stem
      cells (NSCs) from apoptosis. Materials and methods: Transfection was used to
      overexpress Sirt1 in rat NSCs. The effect of Sirt1 overexpression on camptothecin
      induced apoptosis of NSCs was evaluated. Western blotting was used to examine the
      expression of Sirt1, cleaved caspase-3, and acetylated histone 3K9. Results:
      Overexpression of Sirt1 in NSCs decreased the cleavage of caspase-3 and
      acetylation of histone 3K9. Conclusion: Sirt1 may protect NSCs from apoptosis by
      decreasing the acetylation of histone 3 on K9.

PMID- 30233219
TI  - A novel nonlive, adjuvanted herpes zoster subunit vaccine: a report on the
      emerging clinical data and safety profile.
AB  - Herpes zoster (HZ) is an acute vesicular dermatitis with a typical dermatomal
      distribution, caused by the varicella zoster virus (VZV), often preceded and
      accompanied by prodromal pain or pruritus. HZ may be related to several
      complications such as postherpetic neuralgia (PHN). The incidence and severity of
      the disease increase with aging, due to immunosenescence and in particular to the
      decline of the specific cell-mediated immunity (CMI). The impact of HZ in terms
      of morbidity and short- and long-term complications, the availability of
      suboptimal treatment options to date, and the high costs for the diagnostic and
      clinical-therapeutic management of patients have motivated the search for a new
      preventive approach through the development of a vaccine. The vaccine currently
      in use with live-attenuated virus (ZVL) has been shown to be effective in
      reducing the incidence of HZ, its impact, and the onset of PHN, although the
      efficacy is lower in older subjects and tends to decrease some years after
      immunization. A new adjuvanted recombinant subunit vaccine (HZ/su), containing
      the VZV glycoprotein E (gE) and the AS01B adjuvant system, is now a very
      promising alternative to ZVL; in several clinical studies, it showed a good
      safety profile and was able to elicit high immune humoral and cell-mediated
      responses, both maintained up to 9 years. Furthermore, HZ/su vaccine was
      effective both in preventing HZ and in reducing the onset of PHN and other
      complications. HZ/su has been recommended and preferred over ZVL by the Advisory
      Committee on Immunization Practices (ACIP) for the prevention of HZ and its
      complications in immunocompetent adults aged >=50 years, even if already
      vaccinated with ZVL, through a two-dose schedule. HZ/su has been approved in
      Canada, USA, Europe, and Japan and is currently being approved in Australia. The
      aim of this review was to describe the epidemiological data, HZ and PHN risks and
      their impact on the social life and common life of infected people, and ZVL and
      HZ/su vaccine development including various clinical trials and efficacy, safety,
      and tolerability profiles.

PMID- 30233220
TI  - Recurrent tuberculosis among HIV-coinfected patients: a case series from KwaZulu
      Natal.
AB  - Background: Recurrent tuberculosis (TB) following TB treatment completion in HIV
      infected individuals remains a major public health burden. We assessed the role
      of various risk factors in mediating the development of recurrent TB and
      subsequent resistance to antiretroviral therapy and anti-TB drugs. Patients and
      methods: We analyzed secondary demographic, clinical, and laboratory data from
      medical records of five HIV-infected TB patients enrolled between 2009 and 2014
      in a prospective observational study investigating TB recurrence. Paired clinical
      isolates of Myco-bacterium tuberculosis were typed by IS6110 restriction fragment
      length polymorphism analysis to determine the mechanism of TB recurrence. Plasma
      samples were genotyped to determine acquisition of HIV drug resistance mutations
      on antiretroviral treatment (ART). Results: All five patients were HIV
      coinfected, with a previous history of TB infection and prior exposure to anti-TB
      treatment, and residual lung damage, and demonstrated poor treatment adherence -
      significant risk factors linked to the development of recurrent TB disease.
      Furthermore, three of the five patients had multiple episodes of drug-susceptible
      TB infection with subsequent drug-resistant TB infection. Genotyping of the
      initial and recurrent M. tuberculosis isolates demonstrated three cases of
      recurrent TB because of relapse and two because of reinfection. All five patients
      had no mutations at ART initiation; however, by the end of the study follow-up,
      all patients developed dual class resistance. Conclusion: This series
      demonstrates the complexity of recurrent TB in HIV coinfection. We highlight the
      challenges of managing coinfected patients and the increased propensity for the
      development of drug resistance. We report on the role of various risk factors
      mediating the development of resistance and subsequent clinical impact. This
      report underscores the need for structural clinical and adherence interventions
      for the management of complex treatment and dosing.

PMID- 30233221
TI  - Assessing health burden risk and control effect on dengue fever infection in the
      southern region of Taiwan.
AB  - Background: The high prevalence of dengue in Taiwan and the consecutive large
      dengue outbreaks in the period 2014-2015 suggest that current control
      interventions are suboptimal. Understanding the effect of control effort is
      crucial to inform future control strategies. Objectives: We developed a framework
      to measure season-based health burden risk from 2001 to 2014. We reconstructed
      various intervention coverage to assess the attributable effect of dengue
      infection control efforts. Materials and methods: A dengue-mosquito-human
      transmission dynamic was used to quantify the vector-host interactions and to
      estimate the disease epidemics. We used disability-adjusted life years (DALYs) to
      assess health burden risk. A temperature-basic reproduction number (R0)-DALYs
      relationship was constructed to examine the potential impacts of temperature on
      health burden. Finally, a health burden risk model linked a control measure model
      to evaluate the effect of dengue control interventions. Results: We showed that
      R0 and DALYs peaked at 25 degrees C with estimates of 2.37 and 1387,
      respectively. Results indicated that most dengue cases occurred in fall with
      estimated DALYs of 323 (267-379, 95% CI) at 50% risk probability. We found that
      repellent spray had by far the largest control effect with an effectiveness of
      ~71% in all seasons. Pesticide spray and container clean-up have both made
      important contributions to reducing prevalence/incidence. Repellent, pesticide
      spray, container clean-up together with Wolbachia infection suppress dengue
      outbreak by ~90%. Conclusion: Our presented modeling framework provides a useful
      tool to measure dengue health burden risk and to quantify the effect of dengue
      control on dengue infection prevalence and disease incidence in the southern
      region of Taiwan.

PMID- 30233222
TI  - Cost-consequence analysis of fluticasone furoate/vilanterol 92/22 mcg for the
      management of COPD in the Spanish NHS.
AB  - Objectives: The Salford Lung Study in Chronic Obstructive Pulmonary Disease (SLS
      COPD) is a 12-month, open-label randomized clinical trial comparing clinical
      effectiveness and safety of initiating once-daily fluticasone furoate/vilanterol
      (FF/VI) 92/22 mcg with continuing usual care (UC) in patients with COPD followed
      in primary care in the UK. The objective of this analysis is to estimate the
      economic impact of these results when applied to Spain. Materials and methods: An
      Excel-based cost-consequence model with a one-year time horizon was populated
      with SLS COPD results, adopting the Spanish National Health System (NHS)
      perspective. Patients analyzed were diagnosed COPD patients >=40 years old,
      currently managed with maintenance treatment and with a history of exacerbations
      (total number estimated from Spanish data). Mean least squares annual rates of
      moderate/severe exacerbations after 1 year for the intention-to-treat population
      from SLS COPD were included in the model (1.50 [FF/VI] and 1.64 [UC]); serious
      adverse events were excluded from the analysis as no differences between
      treatment arms were found. Medication and exacerbation management costs in euros
      were estimated from Spanish public sources for 2016. Model base-case analysis
      assumed an increased usage of FF/VI from 4% to 10% within 1 year, and a 100%
      proportion of days covered with study medications. Deterministic sensitivity
      analyses were performed for mitigating uncertainty. Results: At base case, within
      50,522 COPD patients analyzed, substitution of UC with FF/VI 92/22 mcg was
      associated with reduced medication and exacerbation management costs, leading to
      potential total annual savings of ?353,623. Deterministic sensitivity results
      ranged from ?218,333 up to ?1,532,366 potential cost savings associated with
      FF/VI, showing the robustness of base-case results. Conclusion: The decreased
      rate of exacerbations with FF/VI 92/22 mcg compared with UC observed in SLS COPD
      could be translated into potential health care savings for the Spanish NHS. These
      results may be useful to inform decision-making processes.

PMID- 30233223
TI  - Cost-effectiveness analysis of voriconazole, fluconazole, and amphotericin B for
      invasive fungal infections following allogeneic hematopoietic stem cell
      transplantation in Mexico.
AB  - Background: Patients receiving allogeneic hematopoietic stem cell transplantation
      (alloHSCT) are at high risk of invasive fungal infections (IFIs), which are
      associated with high mortality and economic burden. The cost-effectiveness of
      prophylaxis for the prevention of IFIs in alloHSCT recipients in Mexico has not
      yet been assessed. Methods: This analysis modeled a hypothetical cohort of 1,000
      patients to estimate costs and outcomes for patients receiving prophylaxis for
      IFIs following alloHSCT, from the perspective of institutional payers in Mexico.
      The main prophylaxis agents currently used in Mexican clinical practice are
      voriconazole, fluconazole, and amphotericin B (AmB). The model accounted for
      event rates of IFIs during each treatment, assuming IFI causality due to invasive
      aspergillosis, invasive candidiasis, or other IFIs, and that the outcome for
      patients during follow-up was IFI-related death, death from other causes, or
      survival. Clinical efficacies were obtained from published literature; costs were
      based on local sources. Cost-effectiveness was assessed using incremental cost
      effectiveness ratios (ICERs). Univariate (assessing the impact of varying each
      model parameter) and probabilistic sensitivity analyses were performed. Results:
      Voriconazole was associated with the lowest number of breakthrough IFIs, IFI
      related deaths, and total number of deaths. Total costs were lower for
      fluconazole (Mexican pesos [MXN] 72,944; US $4,079) than voriconazole (MXN
      101,413; US $5,671) or AmB (MXN 110,529; US $6,180). Voriconazole had better
      clinical outcomes and lower costs than AmB and could be considered cost-effective
      compared with fluconazole in line with the local ICER threshold. Drug costs,
      monitoring costs, and duration of prophylaxis were most sensitive to variation
      from univariate sensitivity analysis. Findings from the probabilistic sensitivity
      analysis were consistent with the base-case results. Conclusion: Voriconazole had
      the most favorable clinical outcomes, but overall prophylaxis costs were higher
      than with fluconazole. Overall, based on local ICER thresholds (MXN 184,665; US
      $10,326), voriconazole was considered a cost-effective option for prophylaxis of
      IFI in Mexico.

PMID- 30233225
TI  - Effects of dextran sulfate, 4-t-butylcyclohexanol, pongamia oil and hesperidin
      methyl chalcone on inflammatory and vascular responses implicated in rosacea.
AB  - Background: Rosacea is a chronic facial skin disorder characterized by
      inflammation and vascular abnormalities. The pathophysiology of rosacea involves
      increased activation of the capsaicin receptor, TRPV1, the vascular endothelial
      growth factor (VEGF) pathway, and cathelicidin LL-37, MMP-9, and KLKs. We
      evaluated the activity of four compounds (dextran sulfate, 4-t-butylcyclohexanol
      [BCH; TRP-regulin(r)], pongamia oil, and hesperidin methyl chalcone [HMC]) on
      inflammatory and vascular responses implicated in rosacea. Materials and methods:
      The anti-inflammatory activity of dextran sulfate was evaluated on PGE2
      production after PMA stimulation of NCTC-2544 keratinocytes, and on normal human
      epidermal keratinocytes (NHEKs) after proinflammatory stimulation to mimic a
      rosacea environment. The anti-angiogenic activity of dextran sulfate was measured
      by analyzing pseudotube formation in co-cultured human microvascular endothelial
      cells/normal human dermal fibroblasts. HMC modulation of vascular responses and
      IL-8 cytokine production after SP stimulation was evaluated in human skin
      explants. We also assessed the effect of BCH on TRPV1 activation, and the effect
      of combined BCH and pongamia oil on the inflammatory response of NHEKs. Results:
      Dextran sulfate strongly and significantly inhibited PMA-induced PGE2 production,
      inhibited KLK5 and MMP-9 mRNA expression, and IL-8, IL-1alpha and VEGF
      production, and displayed a highly significant inhibitory effect on VEGF-induced
      pseudotube formation. In SP-stimulated human skin explants, HMC significantly
      decreased the proportion of dilated vessels, total vessel area, and IL-8
      production. BCH significantly and dose-dependently inhibited TRPV1 activation,
      and BCH and pongamia oil inhibited CXCL1 and CXCL6 mRNA expression and IL-8
      production in NHEKs. Combined BCH/pongamia oil inhibited IL-8 production
      synergistically. Conclusion: These in vitro results showed that dextran sulfate,
      BCH, pongamia oil and HMC, possess complementary soothing and anti-redness
      properties, supporting their combination in Avene redness-relief cosmetic
      products for sensitive skin prone to redness, and for topical adjunctive rosacea
      treatment.

PMID- 30233226
TI  - Achalasia and esophageal cancer: risks and links.
AB  - Esophageal cancer affects more than 4,50,000 persons worldwide, and its incidence
      has increased in recent years. It is the eighth most common cancer across the
      globe. The main histologic types are esophageal squamous cell carcinoma (ESCC)
      and esophageal adenocarcinoma (EA), and their associated risk factors are well
      known. Achalasia, an idiopathic esophageal disorder that conditions aperistalsis
      and the absence of lower esophageal sphincter relaxation, stands out among them.
      The prevalence of ESCC in subjects with esophageal achalasia is 26 in every 1,000
      cases, whereas the prevalence of EA is 4 in every 1,000. Patients with achalasia
      have a 50 times higher risk of presenting with ESCC than the general population,
      and the disease manifests 20-25 years after achalasia symptom onset. Multiple
      mechanisms are related to the development of ESCC in achalasia, and they include
      bacterial overgrowth, food stasis, genetic alterations, and chronic inflammation.
      Regarding the risk of EA in achalasia patients, most cases are associated with
      Barrett's esophagus, due to uncontrolled chronic acid reflux. Given that
      achalasia is a well-established factor for ESCC/EA, clinicians must be aware of
      said associations to enable the development of programs for the prevention and
      opportune detection of these cancers in patients with achalasia.

PMID- 30233224
TI  - Challenging obesity, diabetes, and addiction: the potential of lorcaserin
      extended release.
AB  - Obesity is a global epidemic that is a leading cause of preventable death. In
      addition to lifestyle modification, there are numerous obesity treatments for
      clinicians to consider, including medications. Lorcaserin immediate
      release/extended release (IR/XR) is a US Food and Drug Administration approved
      medication for overweight and obese patients to be used with lifestyle
      modifications. Lorcaserin is thought to reduce weight by targeting the serotonin
      (5HT2c) system to induce satiety. Lorcaserin IR has been shown to be effective in
      reducing weight in overweight (body mass index [BMI] > 27 kg/m2) and obese (BMI >
      30 kg/m2) participants in three large Phase III trials. In addition, lorcaserin
      has been shown to reduce post-cessation weight gain and improved smoking
      cessation in a randomized placebo-controlled trial. A recent meta-analysis
      suggested in overweight diabetic patients lorcaserin may be added to first-line
      oral hypoglycemic medications to enhance reduction in glycated hemoglobin.
      Lorcaserin is generally well tolerated with the most common side effect being
      headache, which is typically self-limiting. Lorcaserin XR (once daily) was
      recently approved and has been shown to be bioequivalent to lorcaserin IR (twice
      daily) in a pivotal study. Lorcaserin XRs, main advantage over the IR formulation
      is the once daily dosing regimen, which likely would lead to improved adherence
      and thus improved clinical effectiveness. The present review will evaluate the
      lorcaserin clinical studies (obesity, diabetes, and addiction), XR bioequivalence
      studies, pharmacogenomics of the serotonin (5HT2c) system, and adherence data in
      once daily versus twice daily medications.

PMID- 30233228
TI  - Optimal cut-off points of lumbar pedicle thickness as a morphological parameter
      to predict lumbar spinal stenosis syndrome: a retrospective study.
AB  - Purpose: Lumbar spinal stenosis syndrome (LSSS) is induced by factors such as
      ligamentum flavum hypertrophy, facet joint hypertrophy and disc degeneration.
      However, the role of lumbar pedicle (LP) in LSSS has yet to be evaluated. We
      devised a new morphological parameter called the lumbar pedicle thickness (LPT)
      to evaluate the connection between LSSS and the LP. We hypothesized that the LPT
      is a major morphological parameter in the diagnosis of LSSS. Patients and
      methods: The LPT data were collected from 136 patients diagnosed with LSSS. A
      total of 99 control subjects underwent lumbar spine magnetic resonance imaging
      (MRI) as part of a detailed medical assessment. Axial T2-weighted magnetic
      resonance (MR) images were acquired from all the participants. Using our picture
      archiving and communication system, we analyzed the thickness of the LP at the
      level of L5 vertebra on MRI. Results: The average LPT was 9.46+/-1.81 mm in the
      control group and 13.26+/-1.98 mm in the LSSS group. LSSS patients showed a
      significantly greater LPT (P<0.001) than the control group. The receiver
      operating characteristic (ROC) curve analysis showed an optimal cutoff point of
      11.33 mm for the LPT, with 83.8% sensitivity, 83.8% specificity and area under
      the curve of 0.92 (95% confidence interval [CI], 0.89-0.96). Conclusion: A higher
      LPT was associated with a higher possibility of LSSS, suggesting its importance
      in the evaluation of patients with LSSS.

PMID- 30233227
TI  - Chronic tonsillitis and biofilms: a brief overview of treatment modalities.
AB  - Recurrent tonsillitis is described as when an individual suffers from several
      attacks of tonsillitis per year. Chronic and recurrent tonsillitis both cause
      repeated occurrences of inflamed tonsils which have a significant impact on a
      patient's quality of life. Numerous children suffer from recurrent tonsillitis
      and sore throats, and these illnesses become part of their life. Antimicrobials
      can provide temporary relief, but in many cases, tonsillitis recurs. The cause of
      such recurrent infections have been identified as microorganisms which often
      create biofilms and a repository of infection in the wet and warm folds of the
      tonsils. This review discusses different treatment modalities, their advantages
      and disadvantages, and new treatment options focusing on biofilms. All treatment
      options should be selected based on evidence and individual need.

PMID- 30233229
TI  - Internet-delivered aftercare following multimodal rehabilitation program for
      chronic pain: a qualitative feasibility study.
AB  - Purpose: Methods for delivering aftercare to help chronic pain patients to
      continue practice self-management skills after rehabilitation are needed.
      Internet-delivered cognitive behavioral therapy (ICBT) has the potential to
      partly fill this gap given its accessibility and emphasis on self-care. Methods
      for engaging and motivating patients to persist throughout the full length of
      treatment are needed. The aim of this study was to describe how chronic pain
      patients work in an ICBT program, through their descriptions of what is important
      when they initiate behavior change in aftercare and their descriptions of what is
      important for ongoing practice of self-management skills in aftercare. Patients
      and methods: Following a multimodal rehabilitation program, 29 chronic pain
      patients participated in a 20-week-long Internet-delivered aftercare program
      (ACP) based on acceptance-based cognitive behavioral therapy. Latent content
      analysis was made on 138 chapters of diary-like texts written by participants in
      aftercare. Results: Attitudes regarding pain and body changed during ACP, as did
      attitudes toward self and the future for some participants. How participants
      practiced self-management skills was influenced by how they expressed motivation
      behind treatment goals. Whether they practiced acceptance strategies influenced
      their continuous self-management practice. Defusion techniques seemed to be
      helpful in the process of goal setting. Mindfulness strategies seemed to be
      helpful when setbacks occurred. Conclusion: Self-motivating goals are described
      as important both to initiate and in the ongoing practice of self-management
      skills. Experiencing a helpful effect of acceptance strategies seems to encourage
      participants to handle obstacles in new ways and to persist throughout treatment.
      Research on whether tailored therapist guidance might be helpful in stating self
      motivating goals and contribute to ongoing practice of self-management skills is
      needed.

PMID- 30233231
TI  - Effect of patient-controlled epidural analgesia versus patient-controlled
      intravenous analgesia on postoperative pain management and short-term outcomes
      after gastric cancer resection: a retrospective analysis of 3,042 consecutive
      patients between 2010 and 2015.
AB  - Background: Effective postoperative analgesia is essential for rehabilitation
      after surgery. Many studies have compared different methods of postoperative pain
      management for open abdominal surgery. However, the conclusions were inconsistent
      and controversial. In addition, few studies have focused on gastric cancer (GC)
      resection. This study aimed to determine the effects of patient-controlled
      epidural analgesia (PCEA) on postoperative pain management and short-term
      recovery after GC resection compared with those of patient-controlled intravenous
      analgesia (PCIA). Methods: We analyzed retrospectively collected data on patients
      with non-metastatic GC diagnosed between 2010 and 2015 who underwent resection in
      a university hospital. PCIA and PCEA documented by the acute pain service team
      were retrospectively analyzed. A propensity score-matched analysis that
      incorporated preoperative variables was used to compare the short-term outcomes
      between the PCIA and PCEA groups. Results: In total, 3,042 patients were
      identified for analysis. Propensity score matching resulted in 917 patients in
      each group. The PCEA group exhibited lower pain scores in the recovery room and
      on the first and second postoperative days (P=0.0005, P=0.0065, and P=0.0034
      respectively). The time to the first passage of flatus after surgery was shorter
      in the PCEA group than in the PCIA group (P=0.032). The length of the hospital
      stay was 12.6+/-7.2 and 11.8+/-6.6 days in the PCEA and PCIA groups,
      respectively. No significant differences were observed in the length of hospital
      stay or the incidence of complications after surgery. Conclusion: PCEA provided
      more effective postoperative pain management and a shorter time to the first
      passage of flatus than PCIA after GC resection. However, it did not have an
      effect on the length of hospital stay or the incidence of postoperative
      complications.

PMID- 30233230
TI  - Anti-allodynic effect of interleukin 10 in a mouse model of complex regional pain
      syndrome through reduction of NK1 receptor expression of microglia in the spinal
      cord.
AB  - Background: To date, there has been no study on the effects of interleukin-10 (IL
      10) on complex regional pain syndrome (CRPS) rodent models, despite the anti
      allodynic effect of IL-10 in previous studies. Thus, the aim of this study was to
      investigate the effect of IL-10 in a CRPS mouse model and find whether early
      inhibition of neuro-inflammation by IL-10 administration, which is considered to
      be one of the important mechanisms in the generation of central sensitization,
      could prevent the transition from the acute stage to the chronic stage of CRPS.
      Method: A mouse model of CRPS (n=6/group) involving tibia fracture/cast
      immobilization to test the efficacy of intrathecal IL-10 (0.3 MUg/5 MUL-1 day-1
      for 7 days) or vehicle during the acute (3 weeks after fracture) stage of CRPS.
      Results: Intrathecal recombinant IL-10 (rIL-10) administration was anti-allodynic
      in the acute stage of the CRPS mouse model, and these anti-allodynic effects of
      IL-10 developed by modulating microglial activation and decreasing NK1 receptor
      expression in the spinal cord. However, intrathecal rIL-10 administration in the
      acute stage of the CRPS mouse model cannot prevent the transition to the chronic
      stage of CRPS in the acute stage of CRPS. Conclusion: Collectively, these results
      demonstrate that intrathecally administered rIL-10 attenuates mechanical
      allodynia in the CRPS mouse model. However, this effect of IL-10 on allodynia in
      the acute stage of CRPS was not sufficient to prevent the transition to the
      chronic stage of CRPS. In the future, further studies about the mechanisms of
      central sensitization in CRPS will be necessary.

PMID- 30233232
TI  - The Pain Registry for Epidemiological, Clinical, and Interventional Studies and
      Innovation (PRECISION): registry overview and protocol for a propensity score
      matched study of opioid prescribing in patients with low back pain.
AB  - Background: Low back pain is the leading cause of disability worldwide.
      Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as the first-line
      pharmacologic therapy for subacute or chronic low back pain, with opioids
      reserved for patients who fail on NSAIDs. CYP2D6, CYP2C9, and CYP2C19 genes have
      variants that place patients using analgesics at risk for adverse events.
      However, precision medicine based on pharmacogenetically informed prescribing is
      becoming more feasible as genotyping costs decline. This study aims to compare
      opioids vs NSAIDs in treating adults with subacute or chronic low back pain under
      the alternative models of usual care and precision medicine. Methods: An
      observational cohort study within the Pain Registry for Epidemiological,
      Clinical, and Interventional Studies and Innovation (PRECISION) will be used to
      simulate a randomized controlled trial. Patients using opioids and NSAIDs will be
      optimally matched at baseline using propensity scores. A saliva sample will also
      be collected to determine patient genotypes for drug metabolism based on CYP2D6
      (single-gene model) and CYP2D6, CYP2C9, and CYP2C19 (multigene model).
      Prescribing that is concordant with pharmacogenetically informed care under these
      models will be considered "low risk", whereas discordant prescribing will be
      considered "high risk". Primary outcomes will be assessed over 6 months using a
      Numerical Rating Scale for pain, the Roland-Morris Disability Questionnaire, and
      the Drug Adverse Events Index. Secondary outcomes will be assessed using quality
      of-life measures. An estimated 600 patients will be enrolled to acquire at least
      400 patients after attrition and allowing for unmatched patients. This will
      achieve a statistical power of at least 80% in detecting the effect sizes ranging
      from 0.35 (small-medium effect) to 0.69 (medium-large effect). Discussion: This
      PRECISION Pain Research Registry study builds on the concepts espoused in the
      Precision Medicine Initiative and addresses long-term goals established by the
      National Institutes of Health by assessing how precision medicine may prevent and
      treat chronic pain.

PMID- 30233233
TI  - Cannabinoids and spinal cord stimulation for the treatment of failed back surgery
      syndrome refractory pain.
AB  - Objective: This study aimed to evaluate pain and its symptoms in patients with
      failed back surgery syndrome (FBSS) refractory to other therapies, treated with a
      combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in
      association with spinal cord stimulation (SCS). Settings: Outpatients referred at
      Pain Unit of San Vincenzo Hospital in Taormina (Italy), between September 2014
      and January 2016. Subjects: Eleven FBSS patients diagnosed with neuropathic pain
      using the Douleur Neuropathique 4 questionnaire and suffering from moderate to
      severe chronic refractory pain, and undergoing treatment with SCS and a
      combination of THC/CBD for 12 consecutive months. Materials and methods: All the
      included patients discontinued previous unsuccessful therapy at least 2 months
      before the beginning of the cannabinoid therapy, with the exception of the SCS
      that was continued. Patients received a fixed dosage of cannabinoid agonists
      (THC/CBD) that could be increased subjective to pain control response. A Brief
      Pain Inventory questionnaire was administered to measure pain and its
      interference with characteristic dimensions of feelings and functions. The
      duration of treatment with SCS and THC/CBD combination was 12 months. Results:
      Effective pain management as compared to baseline result was achieved in all the
      cases studied. The positive effect of cannabinoid agonists on refractory pain was
      maintained during the entire duration of treatment with minimal dosage titration.
      Pain perception, evaluated through numeric rating scale, decreased from a
      baseline mean value of 8.18+/-1.07-4.72+/-0.9 by the end of the study duration
      (12 months) (P<0.001). Conclusion: The results indicate that cannabinoid agonists
      (THC/CBD) can have remarkable analgesic capabilities, as adjuvant of SCS, for the
      treatment of chronic refractory pain of FBSS patients.

PMID- 30233236
TI  - Clinical value of carcinoembryonic antigen for predicting the incidence of brain
      metastases and survival in small cell lung cancer patients treated with
      prophylactic cranial irradiation.
AB  - Background: Although the role of prophylactic cranial irradiation (PCI) in the
      treatment of small cell lung cancer (SCLC) has been confirmed, the occurrence of
      brain metastases (BM) in patients remains a major problem. We designed this study
      to evaluate the clinical value of carcinoembryonic antigen (CEA) for predicting
      the incidence of BM and survival in SCLC patients who received PCI. Materials and
      methods: The records of 128 consecutive SCLC patients, who underwent PCI in our
      institute between 2005 and 2015, were analyzed. The collected data included
      clinicopathological features and the levels of CEA, neuron-specific enolase
      (NSE), cytokeratin 19 fragments (CYFRA21-1), and albumin. Kaplan-Meier and Cox
      regression analyses were used to determine the factors that affect BM and
      survival in SCLC patients after PCI. Results: In total, 128 patients were
      identified, with a median (range) age of 62 (30-83) years. Thirty-two patients
      developed BM at some time during follow-up. The median levels of CEA, NSE,
      CYFRA21-1, and albumin were 7.6 ng/mL, 44 ng/mL, 4.6 ng/mL, and 42.1 g/L,
      respectively. In the multivariate analysis, CEA level (HR: 2.479, 95% CI: 1.101
      5.581; P=0.028), advanced clinical stage (HR: 2.929, 95% CI: 1.338-6.413;
      P=0.007), and NSE level (HR: 3.021, 95% CI: 1.226-7.442; P=0.016) were
      significantly correlated with BM. CEA (HR: 1.903, 95% CI: 1.133-3.195; P=0.015)
      and advanced clinical stage (HR: 2.002, 95% CI: 1.227-3.267; P=0.005) were
      independently associated with worse overall survival in SCLC patients.
      Conclusion: CEA is an independent predictive factor for the incidence of BM after
      PCI in SCLC and can be used as a predictor of BM in SCLC. In addition, a high
      level of CEA indicates a poor prognosis in SCLC patients after PCI. Prospective
      randomized clinical studies are required to confirm these findings.

PMID- 30233235
TI  - Correlation of variable repeat number in the neck regions of DC-SIGN and DC-SIGNR
      with susceptibility to nasopharyngeal carcinoma in a Chinese population.
AB  - Objective: To evaluate the potential association of variations in the number of
      tandem repeats in the dendritic cell-specific intercellular adhesion molecule-3
      grabbing nonintegrin (DC-SIGN) and dendritic cell-specific intercellular adhesion
      molecule-3 grabbing nonintegrin-related (DC-SIGNR) neck region with
      susceptibility to nasopharyngeal carcinoma (NPC). Methods: Variations in the
      number of repeats in the genotypes and alleles in the neck region of DC-SIGN/DC
      SIGNR were analyzed in 477 unrelated NPC patients and 561 cancer-free controls.
      Results: Genotypes and alleles in the DC-SIGN neck region did not differ
      significantly between NPC patients and controls, but the 9-repeat genotype in the
      DC-SIGNR neck region was significantly more frequent among patients (OR 1.339,
      95% CI 1.018-1.760, P=0.037). The association between this genotype and NPC
      remained significant after adjusting for sex, age, smoking history, and presence
      of immunoglobulin against Epstein-Barr virus viral capsid antigen (OR 1.625, 95%
      CI 1.134-2.329, P=0.0082). Conclusion: These results suggest that
      genotypes/alleles in the DC-SIGN neck region are not associated with NPC
      susceptibility, whereas the 9-repeat variant in the neck region of DC-SIGNR may
      increase the risk of NPC.

PMID- 30233237
TI  - Treatment strategies and predicting prognoses in elderly patients with breast
      cancer.
AB  - Objective: The prevalence of breast cancer in elderly women (older than 80 years)
      is expected to rise more dramatically than its incidence. In this study, we
      evaluated the evidence for treatment guidelines for elderly breast cancer
      patients. Patients and methods: All included patients were enrolled from 2010 to
      2013 from the Surveillance, Epidemiology, and End Results (SEER) database. The
      Akaike information criterion (AIC) and Harrell's C statistic were used to perform
      comparisons. In addition, a propensity score analysis was used to avoid bias
      caused by data selection criteria. Prognostic factors were selected as nomogram
      parameters to develop a model to predict survival. Results: A total of 16998
      patients included in the SEER database from 2010 to 2013 had breast cancer and
      fulfilled the study criteria. Of whom, 13007 patients underwent surgery. Overall
      survival and cancer-specific survival were significantly better in patients who
      underwent surgery and/or radiotherapy than in those who did not (P<0.001). In
      addition, a nomogram system with a C index of 0.83 and an AIC index of 11112.85
      was better able to predict prognoses and estimate cancer-specific survival in
      elderly patients with breast cancer. Conclusion: A localized surgical approach
      might provide better results in elderly breast cancer patients. However,
      radiotherapy improved cancer-specific survival and overall survival in these
      patients. In addition, a prognostic nomogram directly quantified patient risk by
      accounting for various prognostic factors without forming risk groups and was
      better able to estimate cancer-specific survival.

PMID- 30233238
TI  - Surgical intervention may be a therapeutic option for NSCLC patients with AJCC
      stage IV: a large population-based study.
AB  - Background: Few studies have focused on the role of surgery in the treatment of
      stage IV non-small cell lung cancer (NSCLC). In our study, we mainly focused on
      the surgical therapeutic option for NSCLC patients with American Joint Committee
      on Cancer stage IV. Patients and methods: Using the Surveillance Epidemiology and
      End Results database, we screened out an appropriate patient population with
      stage IV NSCLC treated between 2004 and 2013. Kaplan-Meier curve analysis was
      used to compare the survival between patients receiving surgery and standard of
      care. The effect of surgery on primary and regional/distant sites on overall
      survival (OS) was further evaluated by Cox proportional hazard model. Finally,
      subgroup analysis based on patient and disease variables was conducted by Cox
      proportional hazard and presented as a forest plot. Results: A total of 61,418
      stage IV NSCLC patients were enrolled. However, only 11.6% received local
      surgical treatment. Surgery to primary and regional/distant sites were both
      independent prognostic factors of OS (P<0.001). Survival advantage was identified
      in those patients who received surgery to primary sites for all subgroup
      variables (P<0.001). However, survival benefit was not demonstrated for patients
      with surgery to regional/distant sites in some subgroup variables, including
      black racial background, squamous cell carcinoma, large cell carcinoma, and N1
      staging (all, P>0.1). Importantly, we observed that surgery of primary tumor
      sites at stage N0 showed the maximum OS benefit (P<0.001). Conclusion: These
      findings about N staging and primary tumor site treatment should be taken into
      consideration by surgeons when determining the suitability of surgery for stage
      IV NSCLC patients.

PMID- 30233234
TI  - IL-17 and colorectal cancer risk in the Middle East: gene polymorphisms and
      expression.
AB  - Background: IL-17 expressed by Th17 cells play a crucial role in tissue
      inflammation by induction of proinflammatory and neutrophil mobilizing cytokines,
      and IL-17 polymorphisms are associated with colorectal cancer (CRC). Objective:
      We investigated the expression of IL-17 and the association of IL-17 gene
      polymorphisms with CRC susceptibility in a Middle East population. Materials and
      methods: The study included 117 diagnosed CRC patients and 100 age- and gender
      matched healthy controls. IL-17A rs2275913 (G197A) and IL-17F rs763780 (T7488C)
      single nucleotide polymorphisms, mRNA, and protein levels of IL-17A were
      assessed. Results: We observed significant association between rs2275913 in IL
      17A and susceptibility to CRC (p = 0.016228). The AG and AA genotypes conferred 2
      fold and 2.8-fold, respectively, higher risk of developing CRC compared with
      individuals having GG genotype. Stratification of the data based on gender and
      age revealed very strong association of CRC with IL17A rs2275913 only in males
      and "AG" genotype in patients <=57 years of age at the time of disease diagnosis.
      The rs763780 in IL-17F was not linked with CRCs in our cohort. Furthermore, IL
      17A mRNA expression in CRCs was significantly elevated compared to adjacent
      normal tissues, particularly in early stages of disease (p = 0.0005). Strong
      immunoreactivity to IL-17A protein was observed in 70% of early stage relative to
      30% of late-stage tumors. Conclusion: The IL-17A G197A variant may be utilized as
      a genetic screening marker in assessing CRC risk, and its expression can be used
      as a biomarker for early detection of CRC in the Saudi population.

PMID- 30233239
TI  - Cervical cancer screening using the Cervista high-risk human papillomavirus test:
      opportunistic screening of a hospital-based population in Fujian province, China.
AB  - Objectives: The Cervista(r) high-risk human papillomavirus (HR-HPV) test was
      evaluated as a primary screening method for cervical cancer in women aged >=21
      years and was compared with different screening and triage combinations.
      Materials and methods: A nested case-control study within the Fujian provincial
      Cervical Lesion Screening Cohorts was used to evaluate the Cervista test as the
      primary cervical screening method in a hospital-based population. Strategy 1
      primarily screened using a cytology screen with HR-HPV testing used for triage.
      Strategy 2 primarily screened using cytology and HR-HPV co-testing. Strategy 3
      primarily screened using HR-HPV testing and triaged HPV-positive women based on
      cytology. Strategy 4 primarily screened using HR-HPV testing and referred A9 pool
      HPV-positive women to colposcopy directly, whereas non-A9 HPV-positive women were
      triaged using cytology. Results: There were 10,183 women included in this study;
      16.49% (1677/10,183) were HR-HPV-positive, 9.52% had abnormal cytology, and 9907
      women were normal during followup. A total of 276 women were diagnosed with
      cervical intraepithelial neoplasia 2 or worse (CIN2+), 197 with CIN3 or worse
      (CIN3+), and 70 with cervical cancer. Moreover, 10.15% (20/197) women who were
      CIN3+ were identified as cytology-negative, while 8.63% (17/197) were HR-HPV
      negative (P>0.05). The cumulative risk rate for HPV-/cytology- was 0.836 (95% CI,
      0.424-1.648) in CIN3+ cases. Strategy 4 yielded the highest sensitivity for CIN2+
      or CIN3+ and the lowest positive predictive value for CIN2+ or CIN3+ among the
      four screening strategies. Conclusion: The Cervista HR-HPV test can provide a
      reliable and sensitive clinical reference for the cervical cancer primary screen.

PMID- 30233240
TI  - Prediction of central lymph node metastasis in papillary thyroid microcarcinoma
      according to clinicopathologic factors and thyroid nodule sonographic features: a
      case-control study.
AB  - Background: Preoperative diagnosis of central lymph node metastasis (CLNM) poses
      to be a challenge in clinical node-negative papillary thyroid microcarcinoma
      (PTMC). This research work aims at investigating the association existing between
      BRAF mutation, clinicopathological factors, ultrasound characteristics, and CLNM,
      in addition to establishing a predictive model for CLNM in PTMC. Materials and
      methods: The study included 673 PTMC patients, already undergone total
      thyroidectomy or lobectomy with prophylactic central lymph node dissection. The
      predictor factors were identified through univariate and multivariate analyses.
      The support vector machine was put to use to develop statistical models, which
      could predict CLNM on the basis of independent predictors. Results: Tumor size
      (>5 mm), lower location, no well-defined margin, contact of >25% with the
      adjacent capsule, display of enlarged lymph nodes, and BRAF mutation were
      independent predictors of CLNM. Through the use of the predictive model, 79.6% of
      the patients were classified accurately, the sensitivity and specificity amounted
      to be 85.1% and 75.8%, respectively, and the positive predictive value and
      negative predictive value stood at 71.6% and 87.6%, respectively. Conclusions: We
      established a predictive model in order to predict CLNM preoperatively in PTMC
      when preoperative diagnosis of CLNM was not clear.

PMID- 30233244
TI  - FOXA1 is upregulated in glioma and promotes proliferation as well as cell cycle
      through regulation of cyclin D1 expression.
AB  - Introduction: Forkhead box A1 (FOXA1) has been found to upregulate in numerous
      cancers, such as ovarian cancer and glioma. However, the detailed function of
      FOXA1 in glioma is still not known. The purpose of this study was to explore the
      underlying mechanism of FOXA1 in glioma cell progression. Methods: The
      expressions of FOXA1 in glioma tissues and cells were determined using
      quantitative reverse transcription-polymerase chain reaction and western blotting
      assays. Wound healing assay and Transwell invasion assay were employed to detect
      the effects of FOXA1 on cellular migration and invasion. Cell Counting Kit-8
      assay, colony formation assay, and flow cytometry analyses were also performed.
      Results: Our study results suggested FOXA1 was upregulated in glioma tissues and
      cells and revealed that FOXA1 promoted glioma cellular proliferation by
      facilitating G1/S transition. Previous work has indicated that CCND1 expression
      is regulated by FOXA1 in ovarian cancer. ChIP and qChIP assay as well as dual
      luciferase reporter assay validated that CCND1 expression was also regulated by
      FOXA1 in glioma cells. Moreover, over-expression of CCND1 in siFOXA1-transfected
      cells partly offsets the effect of FOXA1 inhibition on cellular proliferation.
      Conclusion: FOXA1 promotes glioma cell progression, including cell proliferation
      and cell cycle, by targeting CCND1, and shows potential for the development of
      targeted treatment for glioma.

PMID- 30233241
TI  - A novel SWIM domain protein ZSWIM5 inhibits the malignant progression of non
      small-cell lung cancer.
AB  - Purpose: Zinc finger SWIM-type containing 5 (ZSWIM5) is a newly discovered
      protein, which contains a novel zinc-chelating domain SWIM (CxCxnCxH), and is
      predicted to interact with DNA or proteins. Currently, the knowledge of functions
      of ZSWIM5 remains limited. In this study, we aimed to elucidate the biological
      functions of ZSWIM5 and their mechanisms. Patients and methods: We detected the
      expression of ZSWIM5 in samples from 139 cases of non-small-cell lung cancer
      (NSCLC) patients and six cell lines using immunohistochemistry and Western blot.
      Moreover, we explored the biological functions of ZSWIM5 in lung cancer cells by
      siRNA interference and cDNA transfection of ZSWIM5. Results: The results showed
      that compared with adjacent non-tumor lung tissues, ZSWIM5 expression was
      significantly decreased in NSCLC tissues (P=0.0199) and that the ZSWIM5-positive
      rate in non-tumor tissues (76.67%) was notably higher than that in NSCLC tissues
      (40.29%). ZSWIM5 expression in human normal bronchial epithelial cells was also
      much higher than that in lung cancer lines (P<0.001). ZSWIM5-negative expression
      was significantly related to TNM stage (P<0.001), lymph node metastasis
      (P=0.002), and poor prognosis (P<0.001) of NSCLC patients. MTT and colony
      formation assays showed that ZSWIM5 could inhibit the proliferation and colony
      formation abilities of lung cancer cells. Meanwhile, the results of transwell and
      wound healing assays showed that ZSWIM5 could suppress the invasion and migration
      of lung cancer cells. Further investigation revealed that ZSWIM5 could
      downregulate cyclin D1, cyclin E, cyclin A2, MMP2, and MMP9 expression, which
      affected the proliferation, invasion, and migration abilities of lung cancer
      cells. Conclusion: ZSWIM5 could inhibit the malignant progression of NSCLC by
      affecting the expression of cyclins and MMPs.

PMID- 30233245
TI  - Comprehensive analysis of clinical utility of three-dimensional ultrasound for
      benign and malignant breast masses.
AB  - Background: Three-dimensional (3-D) ultrasound is commonly used for screening
      breast cancer; however, the diagnostic accuracy of this method is unknown. Here,
      we performed a systematic search on the literature to assess the clinical utility
      of 3-D ultrasound in benign and malignant breast masses. Materials and methods:
      We conducted searches in several online databases covering all publications prior
      to August 15, 2017. The bivariate random effects model was used to assess the
      overall sensitivity, specificity, positive likelihood ratio (PLR), negative
      likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary area under
      receiver operating curve (AUC) with their corresponding 95% CI. Results: The
      overall sensitivity of 3-D ultrasound for diagnosing benign and malignant breast
      masses was 89% (95% CI, 83%-93%) and the specificity was 88% (95% CI, 83%-92%)
      with high heterogeneity (I2=81.9; 95% CI, 74.4-89.3, P<0.001). Other parameters
      used to assess efficacy included PLR (5.57; 95% CI, 3.73-8.31), NLR (0.18; 95%
      CI, 0.11-0.28), and DOR (31.33; 95% CI, 15.19-64.61). The use of a Fagan diagram
      with a pretest probability of 20% yields a post-test probability of 65% with a
      PLR of 7. True post-test probability was calculated at 3%, with an NLR of 0.13.
      The summary receiver operating characteristic curve was 0.94 (95% CI, 0.92-0.96),
      with no evidence of publication bias. Conclusion: Three-dimensional ultrasound
      offers high sensitivity and specificity, with a high AUC, indicating a strong
      diagnostic value for detecting benign and malignant breast masses. Three
      dimensional ultrasound may therefore represent an excellent option for secondary
      analysis of unclear breast lesions.

PMID- 30233246
TI  - The role of external beam radiotherapy for hepatocellular carcinoma patients with
      lymph node metastasis: a meta-analysis of observational studies.
AB  - Purpose: Lymph node metastasis of hepatocellular carcinoma is categorized as
      advanced in Barcelona Clinic of Liver Cancer staging, and sorafenib is a sole
      treatment recommended. However, appliance of local treatment including external
      beam radiotherapy (EBRT) has not been uncommon. We performed a meta-analysis and
      systemically reviewed current literature to evaluate the efficacy and safety of
      EBRT. Methods: PubMed, Medline, Cochrane library, and Embase were systemically
      searched until December 17, 2017. The primary endpoint of analyses was response
      rate (RR), and 1-year overall survival and complication rates of grade >=3 were
      secondary endpoints. Complications were primarily assessed descriptively.
      Results: A total of 8 studies comprising 521 patients were included. The pooled
      RR was 73.1% (95% confidence interval [CI]: 63.6-80.9), and high-dose EBRT groups
      had better RR than the low-dose group (82.2% [95% CI: 74.4-88.1] vs 51.1% [95%
      CI: 40.3-61.7]; P=0.001]. The pooled 1-year overall survival rate was 41.0% (95%
      CI: 32.9-49.6). Six studies assessed the survival benefit according to RR, and 5
      (83.3%) of these 6 studies reported statistically significant survival benefit.
      The most common grade >=3 toxicities were thrombocytopenia and gastrointestinal
      complication, with pooled rates of 3.4% (95% CI: 1.2-9.5) and 3.5% (95% CI:1.7
      7.2), respectively. Conclusion: EBRT showed a pooled RR of 73.1% and was safely
      performed. EBRT might palliate symptoms through tumor reductions and improve
      survival. Use of sorafenib combined or sequentially with EBRT can be recommended
      rather than monotherapy.

PMID- 30233247
TI  - Can bone scans guide therapy with radium-223 dichloride for prostate cancer bone
      metastases?
AB  - Background: Radium-223 dichloride (Ra-223 Xofigo) has recently been approved as
      an addition to the host of available therapies in the USA as a treatment option
      for metastatic castrate-resistant prostate cancer (mCRPC) with bone metastases.
      This study describes our initial experience in patients treated with Ra-223
      dichloride. It attempts to optimize patients' selection for the best outcome from
      Ra-223 dichloride therapy. Methods: Consecutive patients who were referred for
      treatment with Ra-223 dichloride were prospectively followed. Patients'
      demographics, functional status per the Eastern Cooperative Oncology Group (ECOG)
      performance score, pain level per the numeric rating score (NRS), prostate
      specific antigen (PSA), creatinine, and hematological values were compared at
      baseline and at the end of therapy. Patients also had a bone scan before starting
      therapy and at the end of therapy. Patients were divided into the favorable
      response (FR) group if their pain and/or functional status improved and the
      unfavorable response (UR) group if they did not improve, deteriorated, or
      deceased. Bone scan findings before and after Ra-223 dichloride therapy were
      compared in both the FR and UR groups. Results: Twenty patients were treated with
      Ra-223 dichloride. Twelve patients had innumerable bone metastases, three
      patients had super scans, and three patients had two to seven bone lesions. Two
      patients were lost to follow-up after the first injection. There were eight
      patients in the FR group and 10 patients in the UR group. Patients with UR had
      mean ECOG and NRS pain scores of 1.3 and 5.0 versus 0.8 and 4.4 in the FR group.
      The mean PSA and creatinine levels in the UR group were 445.2 ng/mL and 1.2 mg/dL
      versus 22.7 ng/mL and 1.1 mg/dL in the FR group. The mean hemoglobin, platelets,
      and absolute neutrophil values were 11.2 g/dL, 314.9 K/cmm, and 7.3 K/cmm in the
      UR group versus 11.6 g/dL, 207.0 K/cmm, and 6.2 K/cmm in the FR group. Seven of
      the eight patients with FR had a bone scan at the end of therapy showing
      improvement in five patients, a mixed response in one patient, and progression in
      another patient. Five patients in the UR group completed five or six injections
      and had bone scans showing flare of bone metastases in three patients,
      progression in one patient, and improvement in the fifth patient. Three patients
      in the UR group died after the first or second injections. Two of these patients
      had baseline super scans and the third one had widespread bone metastases.
      Conclusion: mCRPC patients with lower PSA levels at baseline and fewer bone
      lesions are more likely to respond favorably to Ra-223 dichloride therapy.

PMID- 30233243
TI  - Combination of recurrent oral aphthae and dry eye syndrome may constitute an
      independent risk factor for oral cavity cancer in elderly women.
AB  - Background: Few studies have evaluated the risk of oral cavity cancer (OC) in
      patients with recurrent oral aphthae (ROA) and dry eye syndrome (DES). This study
      assessed the risk of OC in patients who had received diagnoses of ROA and DES in
      Taiwan. Methods: A population-based frequency-matched case-control study was
      conducted in which data were analyzed from the National Health Insurance Research
      Database of Taiwan. Patients with ROA and DES were identified as the case cohort.
      Patients and controls without ROA and DES were frequency matched (1:4) on the
      basis of age, sex, monthly income, geographical location, and urbanization level.
      Chi-squared tests were conducted to compare demographic factor distributions
      between the patients and controls. Cox proportional hazards models were used to
      calculate the adjusted hazard ratios (aHRs) and 95% CI of OC diagnoses among the
      patients and controls. Risk consistency between the two cohorts was determined
      using subgroup analysis. Results: A total of 7,110 patients with ROA and DES and
      28,388 controls were identified. The OC risk was significantly higher for female
      patients than controls (aHR=3.41, 95% CI=1.69-6.86). Furthermore, women aged 50
      69 years exhibited a higher risk of OC than those in the other age groups. Female
      patients aged 50-59 years exhibited the highest aHR for OC (aHR=5.56, 95% CI=1.70
      18.25), followed by those aged 60-69 years (aHR=4.34, 95% CI=1.26-15.99).
      Conclusion: ROA and DES may be associated with a high risk of OC in elderly
      women.

PMID- 30233248
TI  - Musculoskeletal complication in kaposiform hemangioendothelioma without Kasabach
      Merritt phenomenon: clinical characteristics and management.
AB  - Purpose: Musculoskeletal complications have been associated with kaposiform
      hemangioendothelioma (KHE) and can lead to disability and reduced quality of
      life. We aimed to determine the clinical characteristics of musculoskeletal
      complication in patients with KHE without Kasabach-Merritt phenomenon (KMP) in
      order to identify features that may aid clinicians in KHE treatment. Patients and
      methods: We conducted a cohort study of KHE without KMP associated with
      musculoskeletal complication between January 2006 and February 2017 at three
      tertiary medical centers in China. The study included 29 nonthrombocytopenic
      patients with KHE and musculoskeletal complication. Results: The mean age at
      diagnosis of KHE was 4.5 years (range, 0.3-50.0 years). The mean follow-up was
      4.1 years (range, 0.5-9.0 years). In most cases (72.4%), decreased range of
      motion (ROM) appeared within 2 years of KHE onset. Associated chronic pain was
      reported in 12 patients. Bone-joint changes were common in patients with
      decreased ROM (75.9%). All the patients received at least one medical therapy
      including corticosteroids, vincristine, propranolol, and sirolimus. Sirolimus
      demonstrated the highest efficacy rate, with 94.7% of patients showing
      improvements in ROM and chronic pain. Conclusion: Musculoskeletal complication
      can occur early in the disease course of KHE without KMP. Although no uniformly
      effective treatment modality was found, sirolimus demonstrated the best response
      in patients with KHE with decreased ROM and chronic pain.

PMID- 30233250
TI  - Under-recording of hospital bleeding events in UK primary care: a linked Clinical
      Practice Research Datalink and Hospital Episode Statistics study.
AB  - Background: Primary care databases represent a rich source of data for health
      care research; however, the quality of recording of secondary care events in
      these databases is uncertain. This study sought to investigate the completeness
      of recording of hospital admissions for bleeds in primary care records and
      explore the impact of incomplete recording on estimates of bleeding risk
      associated with antithrombotic treatment. Methods: The study population consisted
      of adults with non-valvular atrial fibrillation who had at least one bleed
      recorded in either the Clinical Practice Research Datalink (CPRD) or Hospital
      Episode Statistics (HES) while receiving prescriptions for an oral anticoagulant.
      The proportion of bleeds recorded in HES that had a corresponding bleed recorded
      in the subsequent 12 weeks in CPRD was calculated, and factors associated with
      having a corresponding record were identified. Cox proportional hazards analyses
      investigating the hazard of subsequent bleeding associated with antithrombotic
      treatment were carried out using linked CPRD-HES data and using CPRD only data,
      and the results were compared. Results: Less than 20% of the 14,361 bleeds
      recorded in the HES data had a corresponding bleed coded in the CPRD in the
      subsequent 12 weeks. This proportion varied by bleed characteristics, calendar
      time, day of week of admission (weekday vs weekend) and oral anticoagulant
      treatment at the time of the bleed. The hazard of subsequent bleeding associated
      with vitamin K antagonists (VKAs) and antiplatelet agents (APAs) relative to no
      antithrombotic treatment were similar using the linked primary and secondary care
      dataset (VKA HRadj 1.06 CI95 0.96-1.16; APA HRadj 1.08 CI95 0.96-1.21) and the
      unlinked primary care data (VKA HRadj 1.12 CI95 1.01-1.24; APA HRadj 1.06 CI95
      0.95-1.20). Conclusion: Secondary care bleeding events are not completely
      recorded in primary care records and under-recording may be differential with
      respect to a variety of factors, including antithrombotic treatment. While the
      impact of under-recording on estimates of the comparative safety of
      antithrombotic drugs was limited, the extent of the under-recording suggests its
      potential impact should be considered, and ideally evaluated in future studies
      utilizing standalone primary care data.

PMID- 30233242
TI  - Prognostic value of minichromosome maintenance mRNA expression in early-stage
      pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy.
AB  - Background: The aim of the current study was to investigate the potential
      prognostic value of minichromosome maintenance (MCM) genes in patients with early
      stage pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy by
      using the RNA-sequencing dataset from The Cancer Genome Atlas (TCGA). Methods: An
      RNA-sequencing dataset of 112 early-stage PDAC patients who received a
      pancreaticoduodenectomy was obtained from TCGA. Survival analysis was used to
      identify potential prognostic values of MCM genes in PDAC overall survival (OS).
      Results: Through mining public databases, we observed that MCM genes (MCM2, MCM3,
      MCM4, MCM5, MCM6, and MCM7) were upregulated in pancreatic cancer tumor tissue
      and have a strong positive coexpression with each other. Multivariate survival
      analysis indicated that a high expression of MCM4 significantly increased the
      risk of death in patients with PDAC, and time-dependent receiver operating
      characteristic analysis showed an area under the curve of 0.655, 0.587, and 0.509
      for a 1-, 2-, and 3-year PDAC OS prediction, respectively. Comprehensive survival
      analysis of MCM4 using stratified and joint effects survival analysis suggests
      that MCM4 may be an independent prognostic indicator for PDAC OS. Gene set
      enrichment analysis indicated that MCM4 may participate in multiple biologic
      processes and pathways, including DNA replication, cell cycle, tumor protein p53,
      and Notch signaling pathways, thereby affecting prognosis of PDAC patients.
      Conclusions: Our study indicates that MCM2-7 were upregulated in pancreatic
      cancer tumor tissues, and mRNA expression of MCM4 may serve as an independent
      prognostic indicator for PDAC OS prediction after pancreaticoduodenectomy.

PMID- 30233249
TI  - Prevalent cerebrovascular and cardiovascular disease in people with Parkinson's
      disease: a meta-analysis.
AB  - Background: People with Parkinson's disease (PwP) are speculated to be at a low
      risk of cerebrovascular and cardiovascular disease (CVD) because they have fewer
      vascular risk factors and lower smoking rate. However, emerging evidence suggests
      that PwP are at higher risk of CVD, which introduces controversy to the notion
      that there is no association between Parkinson's disease (PD) and CVD. Hence, we
      conducted a meta-analysis to analyze the risk of CVD in PwP. Methods: Electronic
      databases were searched using terms related to PD and CVD. Articles were included
      in the meta-analysis only if they employed clear diagnostic criteria for PD and
      CVD. The reference lists of the relevant articles were reviewed to identify
      eligible studies not found during the keyword search. Results: The enrolled
      studies were categorized into case-control and cohort studies, and the former was
      further divided into postmortem (three) and clinical (four) studies. In the
      clinical case-control studies group, PD was more associated with CVD (OR: 2.89,
      95% CI: 1.36-6.13). Three studies were enrolled in the cohort studies group, and
      the merged results demonstrated that PwP were at higher risk of CVD during the
      follow-up period (HR: 1.84, 95% CI: 1.34-2.54). Conclusion: PD is associated with
      CVD, which may be due to the shared pathogeneses between the two diseases or PD
      related effects. PwP should be more aware of the risk of CVD despite having fewer
      traditional vascular risk factors.

PMID- 30233251
TI  - Importance of tumor location and histology in familial risk of upper
      gastrointestinal cancers: a nationwide cohort study.
AB  - Background: Familial clustering of upper gastrointestinal (UGI) cancers and the
      significance of family history has been addressed previously. We aimed to
      elucidate the familial risk based on the specified tumor location and histology.
      Method: In the Swedish Family-Cancer Database, we determined the familial risk of
      UGI cancer patients diagnosed (1958-2015) with esophageal and gastric cancer by
      tumor location using standardized incidence ratios (SIRs). Results: Risk of
      esophageal cancer in first-degree relatives (FDRs) of patients with esophageal
      cancer increased 2.4-fold (SIR 95% CI 2.0-2.8), whereas risk of esophageal cancer
      in cases with family history of cancer in the middle third of the esophagus
      increased 3.4-fold (SIR 95% CI 2.1-5.1). Risk of gastric cancer in FDRs increased
      1.6-fold (SIR 95% CI 1.5-1.7), occurrence of concordant subsite gastric cancer in
      the antrum, body, and cardia was 5.5-fold (SIR 95% CI 2.4-11), 4.6-fold (SIR 95%
      CI 2.6-7.4), and 1.7-fold (SIR 95% CI 1.1-2.5), respectively. Familial risk of
      concordant histological subtype in esophageal cancer was 4.1-fold for squamous
      cell carcinoma (SIR 95% CI 3.2-5.2) and 3.6-fold for adenocarcinoma (SIR 95% CI
      2.5-5.1). The risk of concordant gastric adenocarcinoma was 1.6-fold for one
      affected FDR (SIR 95% CI 1.5-1.7), 6.1-fold for two FDRs (SIR 95% CI 4.4-8.4),
      and 8.6-fold among twins (SIR 95% CI 2.3-22). Conclusion: Family history of
      cancer in the lower third of the esophagus and stomach cancer in specific
      locations such as the antrum, body, and cardia can be considered as important
      predictive evidence for cancer in the same location in relatives. Our findings
      might guide endoscopy-based surveillance by introducing subgroups of populations
      with a higher risk for UGI cancer with particular attention to concordance of
      location of lesions, which could be a reasonable strategy for early detection,
      and thus help save more lives.

PMID- 30233254
TI  - Gastric metastasis of ovarian serous cystadenocarcinoma.
AB  - Background: Gastric metastasis from ovarian serous cystadenocarcinoma is
      extremely rare. Case presentation: We herein report one case of a 45-year-old
      female with ovarian carcinoma who underwent cytoreductive surgery. Two years
      later, endoscopic ultrasonography-guided fine needle aspiration revealed gastric
      metastasis. The patient underwent laparoscopic resection of gastric metastases.
      She is currently in complete remission. Conclusion: Gastric metastasis from
      ovarian cancer should not be ignored in the clinic.

PMID- 30233255
TI  - Successful treatment of prosthetic pulmonary valve thrombosis with reteplase: a
      case report.
AB  - Pulmonary prosthetic valve thrombosis is a serious and rare complication with
      high mortality. Using reteplase for treatment of prosthesis thrombosis is rarely
      reported. We report the first case in Iran of a thrombosed pulmonary valve in a
      patient who had undergone repair of tetralogy of Fallot, which was successfully
      treated twice with intravenous thrombolytic therapy with reteplase.

PMID- 30233253
TI  - Medical abortions among university students in Ghana: implications for
      reproductive health education and management.
AB  - Purpose: In Ghana, unsafe abortion is a major cause of maternal mortality. Even
      though pharmaceutical drugs seem to be a key means of unsafe abortion, a paucity
      of evidence exists on the issue among adolescents, students, and other groups at
      risk. This study therefore explores the abortion experiences of Ghanaian
      university students with particular reference to pharmaceutical drugs to fill the
      knowledge gap and enrich the evidence base for reproductive health education,
      policies, and interventions on abortions among students. Patients and methods:
      Undergraduate students from the University of Ghana were randomly selected and
      interviewed. The interviews was recorded, transcribed, and analyzed thematically
      using the framework analysis. Results: Students were aware of safe medical
      abortion services but were reluctant to use them because of cost, stigma, and
      proximity. Generally, medical abortions were more likely to be self-induced among
      students with misoprostol-based drugs administered orally or vaginally. However,
      students also used various over-the-counter drugs, contraceptives, and
      prescription drugs singly, in series, or in combinations to induce abortion. Yet
      students had relatively little knowledge on the inherent risks and long-term
      implications of unsafe medical abortions and were more likely to have repeat
      abortions through unsafe medical methods. Conclusion: Students' knowledge and
      awareness of safe medical abortion avenues have not influenced their propensity
      to use them because of stigma, cost, and other factors. Rather, several methods
      of unsafe medical abortions are used increasingly with dire long-term effects on
      students. Serious knowledge gaps exist among students on the methods and risks of
      medical abortion. Consequently, there is an urgent need to revise current
      abortion management approaches and redirect attention toward reducing stigma and
      financial and social costs of safe abortion services, and increasing the
      proactive engagement, counseling, and management of medical abortions among
      students.

PMID- 30233256
TI  - Rare chemical injuries: a case of ocular superglue instillation in Port Harcourt.
AB  - Background: Ocular superglue injury is uncommon all over the world. Aim: To
      report a case of self-inflicted accidental ocular superglue injury. Methods: A
      case of ocular injury is described in a 29-year-old adult, following inadvertent
      instillation of superglue instead of a prescribed steroid ointment into the right
      eye, in the dark. Results: There was matting of the upper and lower lid margin
      and eyelashes precluding view of the ocular structures. The eyelids were
      separated by gently peeling off the superglue from the lids and lid margins. The
      glue-matted eye lashes were trimmed and the glue on the cornea and conjunctival
      surface was gently removed. Subsequently, a corneal ulcer was seen which was
      managed with topical antibiotics, systemic analgesics, and vitamins. Conclusion:
      Similarity between the tubes of eye ointments and household superglue accounts
      for the accidental eye injury.

PMID- 30233260
TI  - Ulnar collateral ligament injuries of the elbow in female division I collegiate
      gymnasts: a report of five cases.
AB  - Introduction: Elbow ulnar collateral ligament (UCL) injuries in gymnastics have
      not been well documented in the literature, in comparison to UCL injuries in
      baseball. Few studies have examined the mechanism and nonoperative management of
      this injury, and no studies to date have been published on incidence of injury
      and return to play recommendations in gymnastics. Patient case review: A
      literature search was performed using PubMed to review articles from 1980 to 2016
      that addressed the biomechanics of UCL injury in baseball and gymnastics, the
      anatomy of the elbow, injury rates, surgical vs non-surgical management,
      rehabilitation, and return to play recommendations for the sport of gymnastics.
      Five female collegiate gymnasts sustained UCL injury over a 3-year period.
      Electronic medical records for each case were thoroughly reviewed including
      imaging, surgical and non-surgical management, rehabilitation, and the
      progressive return to gymnastics. Discussion: Four UCL injuries were confirmed by
      MRI to be avulsions at the distal insertion of the UCL and one was an avulsion at
      the proximal origin. While less than half of baseball players can return to
      competition with conservative management of these types of injuries, four out of
      five gymnasts were able to return to competition with nonoperative management.
      One gymnast opted to have reconstruction after a successful competition season.
      Time to return to play varied seemingly dependent on the severity of UCL injury
      and event. Conclusion: In our case series, collegiate female gymnasts were able
      to return to participation with nonoperative treatment of the UCL. Their success
      in returning to competitive gymnastics may also depend on the event(s) in which
      they are trying to participate. Strength of Recommendation Taxonomy: C.

PMID- 30233261
TI  - Low mortality rate in Italian rheumatoid arthritis patients from a tertiary
      center: putative implication of a low anti-carbamylated protein antibodies
      prevalence.
AB  - Background and objective: Anti-carbamylated protein antibodies (anti-CarP Ab)
      represent a novel kind of autoantibodies specificity detectable in the sera of
      patients with rheumatoid arthritis (RA). They have been recently reported to be
      associated with increased mortality in Spanish patients with RA. The aim of our
      study was to compare the incidence mortality rates (IMRs) detected in RA patients
      from a tertiary Italian center with those reported in other European tertiary
      centers and to evaluate the putative role of anti-CarP Ab in modulating the low
      IMR detected in our patients. Methods: Clinical charts of patients consecutively
      admitted to our center, from January 1, 2008, to December 31, 2014, were
      retrospectively reviewed. The mortality rate (expressed as the number of deaths
      in the cohort divided by the number of years of IMR follow-up) and causes of
      death were assessed at December 31, 2015. Sera of 61 patients, representative of
      the whole cohort, collected at the time of admission to our center were
      investigated for the presence and the level of anti-CarP Ab. Demographic and
      clinical features, mortality rates and prevalence of anti-CarP Ab in our series
      were compared with those reported in other European cohorts. Results: We observed
      608 patients for a median of 3.51 years. All-cause and cause-specific IMRs in our
      cohort were significantly lower than the Better Anti-rheumatic Farmaco-therapy
      and the Spanish cohort, while only all-cause and cardiovascular IMRs were
      significantly lower in our series with respect to the Leiden Early Arthritis
      Clinic cohort. Anti-CarP Ab prevalence was significantly lower in our series than
      in any other European cohorts. Conclusion: We confirm that the mortality rate is
      lower in our Italian RA cohort with respect to other European cohorts. Whether
      the low prevalence of anti-CarP Ab might be responsible for this result awaits to
      be furtherly investigated.

PMID- 30233258
TI  - VEMP using a new low-frequency bone conduction transducer.
AB  - Objective: A new prototype bone conduction (BC) transducer B250, with an
      emphasized low-frequency response, is evaluated in vestibular evoked myogenic
      potential (VEMP) investigations. The aim was to compare cervical (cVEMP) and
      ocular (oVEMP) responses using tone bursts at 250 and 500 Hz with BC stimulation
      using the B250 and the conventional B81 transducer and by using air conduction
      (AC) stimulation. Methods: Three normal subjects were investigated in a pilot
      study. BC stimulation was applied to the mastoids in cVEMP, and both mastoid and
      forehead in oVEMP investigations. Results: BC stimulation was found to reach VEMP
      thresholds at considerably lower hearing levels than in AC stimulation (30-40 dB
      lower oVEMP threshold at 250 Hz). Three or more cVEMP and oVEMP responses at
      consecutive 5 dB increasing mastoid stimulation levels were only obtained in all
      subjects using the B250 transducer at 250 Hz. Similar BC thresholds were obtained
      for both ipsilateral and contralateral mastoid stimulation. Forehead stimulation,
      if needed, may require a more powerful vibration output. Conclusion: Viable VEMP
      responses can be obtained at a considerably lower hearing level with BC
      stimulation than by AC stimulation. The cVEMP and oVEMP responses were similar
      when measured on one side and with the B250 attached to both ipsilateral and
      contralateral mastoids.

PMID- 30233257
TI  - Propranolol for the treatment of vascular sarcomas.
AB  - Vascular sarcomas are abnormal proliferations of endothelial cells. They range
      from benign hemangioma to aggressive angiosarcoma, and are characterized by
      dysregulated angiogenic signaling. Propranolol is a beta-adrenergic receptor
      inhibitor that has demonstrated clinical efficacy in benign infantile hemangioma,
      and is now being used experimentally for more aggressive vascular sarcomas and
      other cancers. In this review, we discuss the use of propranolol in targeting
      these receptors in vascular tumors and other cancers.

PMID- 30233252
TI  - Operationalization and validation of a novel method to calculate adherence to
      polypharmacy with refill data from the Australian pharmaceutical benefits scheme
      (PBS) database.
AB  - Background: Electronic health care data contain rich information on medicine use
      from which adherence can be estimated. Various measures developed with medication
      claims data called for transparency of the equations used, predominantly because
      they may overestimate adherence, and even more when used with multiple
      medications. We aimed to operationalize a novel calculation of adherence with
      polypharmacy, the daily polypharmacy possession ratio (DPPR), and validate it
      against the common measure of adherence, the medication possession ratio (MPR)
      and a modified version (MPRm). Methods: We used linked health data from the
      Australian Pharmaceutical Benefits Scheme and Western Australian hospital
      morbidity dataset and mortality register. We identified a strict study cohort
      from 16,185 patients aged >=65 years hospitalized for myocardial infarction in
      2003-2008 in Western Australia as an illustrative example. We applied iterative
      exclusion criteria to standardize the dispensing histories according to previous
      literature. A SAS program was developed to calculate the adherence measures
      accounting for various drug parameters. Results: The study cohort was 348
      incident patients (mean age 74.6+/-6.8 years; 69% male) with an admission for
      myocardial infarction who had cardiovascular medications over a median of 727
      days (range 74 to 3,798 days) prior to readmission. There were statins (96.8%),
      angiotensin converting enzyme inhibitors (88.8%), beta-blockers (85.6%), and
      angiotensin receptor blockers (13.2%) dispensed. As expected, observed adherence
      values were higher with mean MPR (median 89.2%; Q1: 73.3%; Q3: 104.6%) than mean
      MPRm (median 82.8%; Q1: 68.5%; Q3: 95.9%). DPPR values were the most narrow
      (median 83.8%; Q1: 70.9%; Q3: 96.4%). Mean MPR and DPPR yielded very close
      possession values for 37.9% of the patients. Values were similar in patients with
      longer observation windows. When the traditional threshold of 80% was applied to
      mean MPR and DPPR values to signify the threshold for good adherence, 11.6% of
      patients were classified as good adherers with the mean MPR relative to the DPPR.
      Conclusion: In the absence of transparent and standardized equations to calculate
      adherence to polypharmacy from refill databases, the novel DPPR algorithm
      represents a valid and robust method to estimate medication possession for multi
      medication regimens.

PMID- 30233259
TI  - Utility of FMS to understand injury incidence in sports: current perspectives.
AB  - The Functional Movement Screen (FMS) is a popular movement screen used by
      rehabilitation, as well as strength and conditioning, professionals. The FMS,
      like other movement screens, identifies movement dysfunction in those at risk of,
      but not currently experiencing, signs or symptoms of a musculoskeletal injury.
      Seven movement patterns comprise the FMS, which was designed to screen
      fundamental movement requiring a balance between stability and mobility. The 7
      movement patterns are summed to a composite FMS score. For an instrument to have
      wide applicability and acceptability, there must be high levels of reliability,
      validity, and accuracy. The FMS is certainly a reliable tool, and can be
      consistently scored within and between raters. Although the FMS has high face and
      content validity, the criterion validity (discriminant and convergent) is low.
      Additionally, the FMS does not appear to be studying a single construct,
      challenging the use of the summed composite FMS score. The accuracy of the FMS in
      screening for injury is also suspect, with low sensitivity in almost all studies,
      although specificity is higher. Finally, within the FMS literature, the concepts
      of prediction and association are conflated, combined with flawed cohort studies,
      leading to questions about the efficacy of the FMS to screen for injury. Future
      research on the use of the FMS, either the composite score or the individual
      movement patterns, to screen for injury or injury risk in adequately powered,
      well-designed studies are required to determine if the FMS is appropriate for use
      as a movement screen.

PMID- 30233262
TI  - Metacognitive approaches to the treatment of psychosis: a comparison of four
      approaches.
AB  - In light of increasing interest in metacognition and its role in recovery from
      psychosis, a range of new treatments focused on addressing metacognitive deficits
      have emerged. These include Metacognitive Therapy, Metacognitive Training,
      metacognitive insight and reflection therapy, and metacognitive interpersonal
      therapy for psychosis. While each of these treatments uses the term
      metacognitive, each differs in terms of their epistemological underpinnings,
      their structure, format, presumed mechanisms of action, and primary outcomes. To
      clarify how these treatments converge and diverge, we first offer a brief history
      of metacognition as well as its potential role in an individual's response to and
      recovery from complicated mental health conditions including psychosis. We then
      review the background, practices, and supporting evidence for each treatment.
      Finally, we will offer a framework for thinking about how each of these
      approaches may ultimately complement rather than contradict one another and
      highlight areas for development. We suggest first that each is concerned with
      something beyond what people with psychosis think about themselves and their
      lives. Each of these four approaches is interested in how patients with severe
      mental illness think about themselves. Each looks at immediate reactions and
      ideas that frame the meaning of thoughts. Second, each of these approaches is
      more concerned with why people make dysfunctional decisions and take maladaptive
      actions rather than what comprised those decisions and actions. Third, despite
      their differences, each of these treatments is true to the larger construct of
      metacognition and is focused on person's relationships to their mental
      experiences, promoting various forms of self-understanding which allow for better
      self-management. Each can be distinguished from other cognitive and skills-based
      approaches to the treatment of psychosis in their emphasis on sense-making rather
      than learning a new specific thing to say, think, or do in a given situation.

PMID- 30233266
TI  - Hypersensitivity in ALK-positive lung cancers exposed to ALK inhibitors: a case
      of successful switch to an alternative ALK inhibitor and systematic review of the
      literature.
AB  - Alectinib can cause rare, but severe hypersensitivity. The cross-reactivity
      between different ALK inhibitors is unknown and desensitization is the only
      reported management. We hereby report the first case of severe delayed
      hypersensitivity developed in a lung cancer patient treated by alectinib, who was
      successfully managed by switching to brigatinib, another ALK inhibitor. The
      patient achieved excellent anti-tumor response to brigatinib. Our case provides
      an alternative and safe strategy in patients with alectinib-related
      hypersensitivity.

PMID- 30233264
TI  - Physical activity and sociodemographic variables related to global health,
      quality of life, and psychological factors in breast cancer survivors.
AB  - Background: Breast cancer is one of the most common cancers affecting women
      worldwide and depression and anxiety are disturbing side effects of cancer
      diagnosis and treatment. The aim of this study was to examine the associations of
      physical activity in global health, quality of life (QoL), and psychological
      factors (depressive symptoms, self-esteem, and anxiety) in breast cancer
      survivors after completing cancer treatment and through survivorship. Demographic
      variables (marital status, education, income), medical status (cancer stage), and
      level of physical activity (metabolic equivalent of task [MET]) were tested as
      predictors of depressive mood, anxiety, self-esteem, and QoL in younger and older
      breast cancer survivors. Materials and methods: One hundred and seventy-one Greek
      breast cancer survivors, who had completed cancer treatment at least one and a
      half years ago, were included in this study. Demographic and medical information,
      self-reported and objective physical activity levels, global health, QoL,
      depressive symptoms, self-esteem, and anxiety were assessed in all participants.
      Results: Active women had lower depressive symptoms, less anxiety, higher self
      esteem, and better global health and QoL, compared to the inactive ones, even in
      the long term after completing treatment through survivorship. Exercise had
      significant positive correlations with self-esteem, global health, and QoL
      (physical, role, emotional, cognitive, and social aspects). Moreover, significant
      negative correlations with anxiety and depressive symptoms were found. Multiple
      regression analysis revealed that MET and covariates such as income, education,
      and stage of cancer were significant predictors of depressive symptoms, self
      esteem, anxiety, global health, and QoL in younger survivors, while MET, income,
      education, stage of cancer, and marital status were significant predictors of
      dependent variables for the older ones. Conclusion: It can be concluded that
      exercise should be recommended to cancer survivors even after treatment
      completion and through survivorship to achieve higher self-esteem, better QoL,
      and decreased anxiety and depressive symptoms.

PMID- 30233267
TI  - Model for allocation of medical specialists in a hospital network.
AB  - Introduction: As human diseases are becoming increasingly complex, the need for
      medical specialist consultation is more pronounced, and innovative ways to
      allocate medical specialists in hospital networks are essential. This study aimed
      to construct allocation models using a multi-objective programming approach in a
      large private hospital network in Thailand. Methods: Our study included 13
      medical specialist types in four main disease groups of the Bangkok Dusit Medical
      Services network. Mixed-integer linear programming models were developed using
      inputs from a modified Delphi survey of executives, the Physician Engagement
      Survey, and the Physician Registry (PR) databases and featuring three objectives:
      1) minimizing travel expense, 2) optimizing physician engagement, and 3)
      maximizing the chance of direct patient encounters with respective medical
      specialists who were formally qualified for the clinical complexity of the
      patients, as measured by the case mix index (CMI). Results: The constructed
      models included the core components but varied by a combination of whether part
      time medical specialists are included or not (noPT) and whether CMI is included
      (CMI) or not (noCMI). Because the noPT + CMI model had the highest capability to
      solve for specialist allocation, it was further improved for some specialist
      types in terms of flexibility for sensitivity analysis of the variables.
      Moreover, to assess the feasibility and practicality of the models, a web-based
      system incorporating the final model was developed to support the central
      executives' decision to allocate medical specialists to the network, especially
      for finding the most optimal and timely solution for widespread shortages.
      Conclusion: The linear programming models that accommodate critical components
      for allocating medical specialists in the hospital network were feasible and
      practical for the central executives' timely decision making. The models could be
      further tested for their application in hospitals in the public sector or other
      private hospital networks.

PMID- 30233263
TI  - Interpersonal psychotherapy for eating disorders: current perspectives.
AB  - Background: Interpersonal psychotherapy (IPT) is a time-limited and affect-, life
      event-, and present-focused psychotherapy originally conceptualized for unipolar
      depression, and then adapted to the treatment of other disorders, including
      eating disorders (EDs). The purpose of this paper is to conduct a systematic
      review of studies on IPT for EDs. Methods: The authors performed literature
      searches, study selection, method, and quality evaluation independently. Data
      were summarized using a narrative approach. Results: Of the 534 papers retrieved,
      37 studies met the inclusion criteria, and 15 were considered for the systematic
      review (randomized controlled trials and long-term follow-up studies derived from
      the randomized controlled trials). Their analysis revealed six main findings: 1)
      no significant differences between IPT and cognitive-behavioral therapy (CBT)
      were found when administered as monotherapy to patients with anorexia nervosa; 2)
      when administered as monotherapy to patients with bulimia nervosa (BN), IPT had
      lower outcomes than CBT and its enhanced version; 3) patients with BN who
      remitted with IPT showed a prolonged time spent in clinical remission, when
      followed up on the long term; 4) IPT and CBT, with different timings and methods,
      have both shown efficacy in the mid-term/long-term period in patients with BN; 5)
      CBT and its enhanced version produced rapid changes in the acute phase. IPT led
      to improvements occurring later, with slower changes that tended to maintain
      efficacy in the long term; 6) abstinence from binge eating with group IPT for
      binge eating disorder is stable and maintained (or further improved) in the long
      term. Conclusion: IPT is a reasonable, cost-effective alternative to CBT for the
      overall ED spectrum.

PMID- 30233268
TI  - MBBS teaching program, according to DREEM in College of Medicine, University of
      Bahri, Khartoum, Sudan.
AB  - Introduction: Learning environment might be defined as anything that can affect
      the learning directly or indirectly. During the era of accreditation and quality
      assurance, we are badly in need to evaluate our program strength and pick
      possible areas for curriculum reform. Objectives: The aim of this study was to
      investigate the perception of medical students in the University of Bahri (UB)
      about the educational environment and analyze the variation of this perception
      with gender, level of study, type of intake, type of certificate, and
      accommodation. Methodology: This is a cross-sectional study that was conducted at
      the Faculty of Medicine, UB, in Sudan during July-August 2017, enrolling 347
      students. Dundee Ready Education Environment Measure (DREEM) questionnaire was
      used as a survey tool for this study. Results: Overall DREEM average score of
      125.2997/200 is perceived. This score is distributed in all DREEM subclasses.
      Conclusion: Having some negative perceptions is a huge burden on policymakers,
      administration, and all stakeholders to revise the whole educational environment
      at the UB with special efforts needed for curriculum revision, faculty
      development, mentoring, and other skills development.

PMID- 30233273
TI  - China's dam-builders: their role in transboundary river management in South-East
      Asia.
AB  - This article investigates China's role as the world's largest builder of and
      investor in large dams, focussing on the Greater Mekong Sub-Region in South-East
      Asia. It addresses the role Chinese actors play in dam-building as well as the
      environmental, social, economic and political implications by drawing on case
      studies from Cambodia and Vietnam. The article finds that China's dam-building is
      perceived very differently in different countries of South-East Asia. In
      Cambodia, the dams in the Greater Mekong Sub-Region are considered instruments of
      economic growth and development, whereas downstream in Vietnam the dams are seen
      as potentially undermining national growth, development and security.

PMID- 30233269
TI  - The efficacy of self-directed learning versus problem-based learning for teaching
      and learning ophthalmology: a comparative study.
AB  - Introduction: Self-directed learning (SDL) and problem-based learning (PBL) are
      fundamental tools to achieve lifelong learning in an integrated medical
      curriculum. However, the efficacy of SDL in some clinical courses is debated.
      Aim: The aim of the study was to measure the effectiveness of SDL for an
      ophthalmology course in comparison with PBL. Methods: A cross-sectional study was
      conducted with fifth-year medical students enrolled in an ophthalmology course.
      SDL comprised four case-based scenarios guided by several questions. PBL
      comprised three sessions. An ear, nose, and throat (ENT) course was selected for
      comparison as a control. At the end of the course, 30 multiple-choice questions
      (MCQs) for both SDL and PBL were assessed and analyzed against their counterparts
      in the ENT course by an independent t-test. Results: For the SDL component of the
      ophthalmology course, the number and percentages of students attaining high (n =
      6/60, 10%) and moderate (n = 15/60, 28.3%) scores on an MCQs written exam were
      evaluated. For the PBL component, high scores were seen for 23.3% (n = 14/60),
      and moderate scores for 33.3% (n = 20/60) of the participants. For the SDL
      component of the ENT course, the number and percentages of students attaining
      high (n = 14/60, 23.3%) and moderate (n = 17/60, 28.3%) scores were recorded. For
      the PBL component, high (16/60, 26.6%) and moderate (17/60, 28%) scores were
      recorded. Significant p-values were obtained between the results for SDL and PBL
      in the ophthalmology course (p = 0.009), as well as between SDL results for both
      courses (p = 0.0308). Moreover, differences between the SDL results of
      ophthalmology and the PBL results of ENT (p = 0.0372) were significant.
      Conclusion: SDL appears to be less valuable for promotion of self-readiness.
      Periodic discussions in small groups or by panel discussion are strongly
      recommended for students to enhance readiness with SDL.

PMID- 30233274
TI  - Residential Segregation is the Linchpin of Racial Stratification.

PMID- 30233275
TI  - Summary of Antiepileptic Drugs Available in the United States of America: WORKING
      TOWARD A WORLD WITHOUT EPILEPSY.

PMID- 30233271
TI  - The impact on internship of a tailored intern preparation package.
AB  - Introduction: On commencing internship, new medical graduates (new interns) are
      often required to perform core procedural skills under differing levels of
      supervision. This variability of knowledge and experience with procedural skills
      can place patient safety at risk. Consequently, in 2012, we developed a targeted,
      intensive, 3-day training course for our pre-intern (PrInt) students. The aim of
      this study was to evaluate the intern preparation package by exploring interns'
      self-reported knowledge, confidence, and experience in key procedural skills
      during the early months of internship. Methods: Between 2012 and 2016, 5 cohorts
      of PrInt students (n=223) participated in our course. In the following years 2013
      2017, the same 5 cohorts, at 4-5 months into their internship, were surveyed
      anonymously and invited to attend focus groups. Descriptive statistics and
      thematic analysis were used to analyze data. Results: Of the 223 interns, 91
      (41%) responded. Of the 91, 82 (93%) agreed that the intern preparation package
      provided during PrInt had been beneficial to their practice as an intern.
      Awareness of potential risks to patient safety was high, ranging from infection
      control at 89/89 (100%) to 87/90 (97%) for patient identification. Confidence in
      performing procedural skills varied from moderate in identifying nasogastric tube
      placement on X-ray (66/89; 85%), to equal least confidence in managing cardiac
      related emergencies (53/90; 59%) and identifying the correct placement of
      peripherally inserted central catheter lines on X-ray (52/89; 58%). Major
      qualitative findings: The preparation package had refreshed interns' procedural
      skills ability and awareness of risks to patient safety. Integration into the
      clinical team was positive, but requests to perform procedural skills on day 1
      was unexpected. Conclusion: Interns reported that they had gained substantial
      benefit from their preparation package, and they performed practical procedures
      from day 1, further highlighting the need for an intensive preparation course
      immediately prior to entering internship.

PMID- 30233270
TI  - Relationship between poor quality sleep, excessive daytime sleepiness and low
      academic performance in medical students.
AB  - Purpose: Poor quality of sleep and excessive daytime sleepiness affect cognitive
      ability and have a negative impact on the academic performance of medical
      students. This study aims to determine the prevalence of excessive daytime
      sleepiness, sleep quality and psychological distress as well as assess their
      association with low academic performance in this population. Participants and
      methods: A cross-sectional study was conducted among 457 medical students from
      the Faculty of Medicine and Pharmacy of Rabat, Morocco, who completed the
      Pittsburgh Sleep Quality Index (PSQI) questionnaire and the Epworth Sleepiness
      Scale to determine the quality of sleep and excessive daytime sleepiness,
      respectively. Sociodemographic variables and psychological distress (Kessler
      Psychological Distress Scale) were also measured. Multivariate linear regression
      was performed in order to evaluate the link between low academic performance and
      sleep quality after adjusting for other covariates. Results: Among the included
      students, the median age was 20 (19; 21) years; 70.7% of the participants were
      females. Almost one-third of the students (36.6%) had excessive daytime
      sleepiness and this was more frequently observed in female students (43% vs
      20.1%, <0.001). Furthermore, 58.2% of the students were poor sleepers (PSQI >=5),
      while 86.4% of them had psychological distress. The bivariate analysis showed
      that psychological distress was associated with decreased risk of low performance
      (beta=0.04; 95% CI=0.005-0.07; P=0.024). Being a poor sleeper was statistically
      associated with poor academic performance (beta= -0.07; 95% CI=-0.14 to -0.002;
      P=0.04) in the multivariate analysis. In our study, daytime sleepiness was not
      statistically associated with academic performance. Conclusion: A poor sleep
      quality determined by PSQI >=5 was related to poor academic achievement at the
      end of the study year in medical students.

PMID- 30233272
TI  - Continuous noninvasive ventilation for respiratory failure in patients with
      amyotrophic lateral sclerosis: current perspectives.
AB  - Respiratory failure is a recognized late complication of amyotrophic lateral
      sclerosis. It is related to the neurological progression of the diseases with the
      impairment of the respiratory musculature. Survival and quality of life of
      amyotrophic lateral sclerosis patients is improved by using noninvasive
      mechanical ventilation. The rate of long-term mechanical ventilation is different
      within and between countries. Cultural factors, socioeconomic conditions, and
      physician attitude often influence the decision to start noninvasive ventilation.
      Technical elements, like the choice of the correct interface, solid caregivers
      support, and the communication between the patient and the physician are
      essential for achieving therapeutic goals, especially in the case of continuous
      treatment.

PMID- 30233265
TI  - Obstructive sleep apnea: focus on myofunctional therapy.
AB  - Purpose: Orofacial myofunctional therapy (OMT) is a modality of treatment for
      children and adults with obstructive sleep apnea (OSA) to promote changes in the
      musculature of the upper airways. This review summarizes and discusses the
      effects of OMT on OSA, the therapeutic programs employed, and their possible
      mechanisms of action. Methods: We conducted an online literature search using the
      databases MEDLINE/PubMed, EMBASE, and Web of Science. Search terms were
      "obstructive sleep apnea" in combination with "myofunctional therapy" OR
      "oropharyngeal exercises" OR "speech therapy". We considered original articles in
      English and Portuguese containing a diagnosis of OSA based on polysomnography
      (PSG). The primary outcomes of interest for this review were objective
      measurement derived from PSG and subjective sleep symptoms. The secondary outcome
      was the evaluation of orofacial myofunctional status. Results: Eleven studies
      were included in this review. The studies reviewed reveal that several benefits
      of OMT were demonstrated in adults, which include significant decrease of apnea
      hypopnea index (AHI), reduced arousal index, improvement in subjective symptoms
      of daytime sleepiness, sleep quality, and life quality. In children with residual
      apnea, OMT promoted a decrease of AHI, increase in oxygen saturation, and
      improvement of orofacial myofunctional status. Few of the studies reviewed
      reported the effects of OMT on the musculature. Conclusion: The present review
      showed that OMT is effective for the treatment of adults in reducing the severity
      of OSA and snoring, and improving the quality of life. OMT is also successful for
      the treatment of children with residual apnea. In addition, OMT favors the
      adherence to continuous positive airway pressure. However, randomized and high
      quality studies are still rare, and the effects of treatment should also be
      analyzed on a long-term basis, including measures showing if changes occurred in
      the musculature.

PMID- 30233277
TI  - Ellman's method is still an appropriate method for measurement of cholinesterases
      activities.

PMID- 30233278
TI  - Glyphosate toxicity and carcinogenicity.

PMID- 30233280
TI  - Occupational stress among nurses and pre-hospital emergency staff: application of
      fuzzy analytic hierarchy process (FAHP) method.
AB  - Healthcare professionals, especially nurses and pre-hospital emergency (PHE)
      staff, are influenced by many stressors due to their responsibility to provide
      comfort as well as care and treatment of patients. The aim of the present study
      was to identify and rank the occupational stressors in nurses and PHE staff using
      Fuzzy Analytic Hierarchy Process (FAHP) method. In this cross-sectional study,
      occupational stress factors in nurses and PHE staffs were identified and ranked
      by 30 experts, using FAHP method. Occupational stress factors were collected by
      General Health Questionnaire (GHQ), Job Stress Questionnaires as well as a
      literature review. Among the occupational stress factors in nurses, the highest
      scores were related to "Incompatibility between work schedule and life
      conditions" (0.03986) and "Being criticized by supervisors" (0.03723),
      respectively. The most common stress factors in PHE staff were related to "Care
      of patients with critical health conditions" (0.07258), "High number of missions"
      (0.07056), respectively. The overall results of this study showed that managerial
      factors and factors related to patient care are the most important causes of
      occupational stress among nurses and PHE staff. These factors should be
      considered in the implementation of control strategies for reducing and managing
      occupational stress.

PMID- 30233282
TI  - Repositioning of 8-hydroxyquinoline derivatives as a new promising candidate for
      combating multidrug resistant Neisseria gonorrhoeae.
AB  - The multidrug resistance of Neisseria gonorrhoeae becomes a public health problem
      worldwide, especially the strain H041 that showed the decrease susceptibility to
      ceftriaxone which is the last resort for gonorrhea treatment. Therefore, the
      simultaneous discovery and development of a new compound to fight this pathogen
      is urgently required. In this study, 8-hydroxyquinoline (8HQ) and derivatives
      were evaluated for their antimicrobial activities against the gonococcal pathogen
      using spectinomycin as the reference drug. The results showed that 8HQ
      derivatives gave an excellent antimicrobial potency. Particularly, the
      dihalogenated 8HQ (iodoquinol, clioquinol and 5,7-diCl-8HQ) exerted the high
      activity with MIC range of 0.08-0.15 MUM, 0.10-0.20 MUM and 0.28-0.56 uM,
      respectively, compared with the reference drug (MIC = 16 MUg/mL or 48.14 MUM).
      Moreover, these compounds were also shown to be non-cytotoxic/very high safety
      index. The findings reveal that these three compounds could be further developed
      as a new antimicrobial agent for fighting the gonorrheal disease.

PMID- 30233281
TI  - Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin
      resistance and spatial memory impairment: effects of insulin treatment.
AB  - Despite the consensus that neuro-inflammation and insulin resistance (IR) are two
      hallmarks of Alzheimer disease (AD), the molecular mechanisms responsible for the
      development of IR remain uncharacterized. MAPKs are signaling molecules that are
      implicated in the pathology of AD and have a role in IR development. Given that
      inflammatory mediators are shown to interfere with insulin signaling pathway in
      different cell types, the present work aimed to investigate whether neuro
      inflammation induced memory loss is associated with hippocampal IR and whether
      insulin treatment protects against this IR. Subsequently, possible roles of MAPKs
      in this situation were investigated. Male Wistar rats were cannulated, and LPS
      (15 ug, day 0), insulin (3 mU) or saline (vehicle) were administered intra
      cerebroventricularly (ICV) (days 1-6). Spatial memory performance was assessed
      during days 7-10 by Morris Water Maze test. Consequently, analysis of the amount
      of hippocampal phosphorylated forms of P38, JNK, ERK, IRS1 (ser307) and Akt
      (ser473) were done by Western blot. The outcomes indicated that while LPS induced
      memory loss and hippocampal IR (shown by elevated IRS1 and decreased Akt
      phosphorylation), insulin treatment nullified these effects. Molecular results
      also showed that LPS mediated IR and memory loss are associated with P38 but not
      JNK and ERK activation; this P38 activation was reversed by insulin treatment.
      These observations implied that one of the ways by which neuro-inflammation
      participates in AD is via induction of IR. It seems that this IR is mainly
      mediated by P38. Therefore, P38 could be considered as a molecular target for
      preventing IR development.

PMID- 30233279
TI  - Non-random distribution of gastric cancer susceptible loci on human chromosomes.

PMID- 30233276
TI  - The aryl hydrocarbon receptor in T cells contributes to sustaining oral tolerance
      against ovalbumin in a mouse model.
AB  - Oral tolerance (OT) towards antigens encountered in the gut is a vital immune
      function of gut immunity. Experimental models can demonstrate OT efficacy by
      feeding of a protein followed by peripheral immunization and measuring the
      specific antibody titer. We had previously shown that exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), a xenobiotic high-affinity aryl hydrocarbon
      receptor (AhR)-ligand, destabilized OT against ovalbumin (OVA) in mice. AhR is
      involved in the development, differentiation and function of immune cells, and
      highly expressed in gut epithelial cells and gut immune cells. We here used AhR
      deficient mice to study the role of AhR in OT further. We show that complete AhR
      deficiency undermines the stability of oral tolerance against OVA upon multiple
      immunizations, despite no renewed oral encounter with the antigen. This OT
      destabilization is accompanied by significant changes in IL10 and TGFbeta RNA in
      the gut tissue. Using conditional AhR-deficient mouse lines, we identify T cells
      as the major responsible immune cell type in this context. Our findings add to
      knowledge that lack of AhR signaling in the gut impairs important gut immune
      functions.

PMID- 30233283
TI  - ARG1 single nucleotide polymorphisms rs2781666 and rs2781665 confer risk of Type
      2 diabetes mellitus.
AB  - Genetic polymorphisms mapped in the ARG1 locus (chr6:131894344-131905472) and
      their functional effects on type 2 diabetes mellitus (T2DM) have not been
      thoroughly elucidated to date. The present study aimed to investigate an
      association between variant alleles at ARG1 locus and T2DM in patients. Two ARG1
      single nucleotide polymorphisms (SNPs) were characterized in a representative
      sample of 500 patients with T2DM and 500 healthy volunteers. Serum lipid profile
      was studied by spectrophotometric analysis, while serum arginase-1 concentrations
      were determined by an enzyme-linked immunosorbent assay. The regions,
      encompassing target SNPs (rs2781665 and rs2781666), were amplified by polymerase
      chain reaction and genotypes were assigned by restriction digestions. A
      statistically significant increase was observed in the serum hs-CRP and arginase
      1 levels in the subjects with T2DM than in controls (P <0.0001; for each). The
      variant genotypes of rs2781666 and rs2781665 were significantly associated with
      T2DM when compared with controls (P< 0.0001). Moreover, type 2 diabetic patients
      showed higher frequencies of T allele at rs2781666 and rs2781665 compared to the
      controls (OR = 1.7; 95 % CI=1.31-2.13; P <0.0001, and OR = 1.9; 95 % CI=1.45
      2.38; P <0.0001, respectively). Haplotype T-T (chr6: 131893247-131893559) mapped
      at rs2781665-A/T and rs2781666-G/T displays higher frequency in the subjects when
      compared to the healthy ethnically-matched control samples (P <0.0001). We wish
      to propose, the first ever observation to our knowledge that concluding high
      levels of arginase-1 and the ARG1 polymorphisms are possible causes to
      confer/augment the risk of T2DM in subjects originates in Pakistan.

PMID- 30233284
TI  - Quercetin and its role in biological functions: an updated review.

PMID- 30233285
TI  - Effect of elaidic acid on ABCA1 expression in raw 264.7 cells. Is it through PPAR
      gamma?
AB  - In recent years, Trans Fatty Acids have shown a strong correlation with
      cardiovascular disease. However, the mechanisms explaining their atherogenicity
      are still unclear. ABCA1, which is involved in the reverse cholesterol transport
      pathway, has been considered as a new therapeutic target for cardiovascular
      disease. In vitro studies of the effects of PPAR-gamma on lipid homeostasis in
      macrophage cells suggested a role for PPAR-gamma in the regulation of ABCA1
      dependent cholesterol efflux to apoA-I pathway. Thus, in this study we examined
      the effect of elaidic acid (EA) as the most abundant TFA on expression of ABCA1
      and PPAR-gamma in RAW 264.7 mouse macrophage cell line. Accordingly, after
      determining appropriate concentrations of EA using MTT, RAW 264.7 cells were
      treated with different concentrations of EA, and at the end, gene expression was
      assayed by Real-Time PCR. Our results shown that the expression of ABCA1
      decreased in the treated group in comparison with the control group by 1.7, 2.3,
      and 5.1 fold, after 12 h treatment for 0.5, 1, and 2 mM EA concentration
      respectively. In addition, after 24 h treatment with EA, the rate of decreasing
      ABCA1 expression was 2.1, 2.6, 5.7 fold, respectively (P < 0.01). However, EA had
      no significant effect on PPAR-gamma mRNA expression. Therefore, it could be
      concluded that the atherogenic effect of EA may be mediated by reducing ABCA1
      expression in RAW 264.7 cells; however, this reduction has not mediated through
      altering PPAR-gamma expression.

PMID- 30233286
TI  - Regenerative potential of partially differentiated mesenchymal stromal cells in a
      mouse model of a full-thickness skin wound.
AB  - Mesenchymal stromal cells (MSCs, known as mesenchymal stem cells) are considered
      to be a promising therapeutic tool for many diseases. But it is still unclear
      which cells are more efficient and safe for wound healing and tissue regeneration
      for clinical applications: undifferentiated, partially differentiated stem cells
      or differentiated cells. In this study, we modified MSCs with keratinocyte
      conditioned medium (KCM) and examined MSCs, partially differentiated MSCs (PMSCs)
      and differentiated cell migration, accumulation in the wounded area as well as
      cell regenerative efficiency in a full-thickness skin wound model. In addition to
      that, the impact of intradermal and intravenous cell delivery methods of wound
      healing was evaluated. C57BL/6J mouse compact bone MSCs were treated with a KCM
      for 14 days. Flow cytometry analysis showed the appearance of keratinocyte
      surface markers which were absent in MSCs, whereas the specific markers for MSCs
      were lost. Cells were injected either intravenously or intradermally in C57BL/6J
      mice. Wound closure, cell migration and accumulation in the wounded area were
      further analysed. Wound healing was assessed by the rate of wound closure and by
      histological evaluation. Cells were monitored using optical imaging. We
      demonstrated that PMSCs showed morphology similar to keratinocyte cells, had
      enhanced migration and increased survival at the site of injury. PMSCs had a
      beneficial effect on wound healing and tissue regeneration. This effect was
      reinforced when these cells were injected intravenously. Due to their partial
      differentiation status, we assume that PMSCs can differentiate more rapidly into
      epidermal cell lineages thus causing faster and qualitatively improved wound
      healing.

PMID- 30233295
TI  - Deep Supervised Learning Using Local Errors.
AB  - Error backpropagation is a highly effective mechanism for learning high-quality
      hierarchical features in deep networks. Updating the features or weights in one
      layer, however, requires waiting for the propagation of error signals from higher
      layers. Learning using delayed and non-local errors makes it hard to reconcile
      backpropagation with the learning mechanisms observed in biological neural
      networks as it requires the neurons to maintain a memory of the input long enough
      until the higher-layer errors arrive. In this paper, we propose an alternative
      learning mechanism where errors are generated locally in each layer using fixed,
      random auxiliary classifiers. Lower layers could thus be trained independently of
      higher layers and training could either proceed layer by layer, or simultaneously
      in all layers using local error information. We address biological plausibility
      concerns such as weight symmetry requirements and show that the proposed learning
      mechanism based on fixed, broad, and random tuning of each neuron to the
      classification categories outperforms the biologically-motivated feedback
      alignment learning technique on the CIFAR10 dataset, approaching the performance
      of standard backpropagation. Our approach highlights a potential biological
      mechanism for the supervised, or task-dependent, learning of feature hierarchies.
      In addition, we show that it is well suited for learning deep networks in custom
      hardware where it can drastically reduce memory traffic and data communication
      overheads. Code used to run all learning experiments is available under
      https://gitlab.com/hesham-mostafa/learning-using-local-erros.git.

PMID- 30233288
TI  - High-Fat Feeding Improves Anxiety-Type Behavior Induced by Ovariectomy in Rats.
AB  - Menopause-induced changes may include increased incidence of both
      depression/anxiety and obesity. We hypothesized that behavioral changes that may
      develop after ovarian failure could be related to neurochemical and metabolic
      aspects affected by this condition and that high-fat intake may influence these
      associations. The present study investigated in rats the effects of ovariectomy,
      either alone or combined with high-fat diets enriched with either lard or fish
      oil, on metabolic, behavioral and monoaminergic statuses, and on gene expression
      of neuropeptides and receptors involved in energy balance and mood regulation.
      Female rats had their ovaries removed and received either standard chow (OvxC) or
      high-fat diets enriched with either lard (OvxL) or fish-oil (OvxF) for 8 weeks.
      The Sham group received only chow diet. Ovariectomy increased feed efficiency and
      body weight gain and impaired glucose homeostasis and serotonin-induced
      hypophagia, effects either maintained or even accentuated by the lard diet but
      counteracted by the fish diet. The OvxL group developed obesity and
      hyperleptinemia. Regarding components of hypothalamic serotonergic system, both
      ovariectomy alone or combined with the fish diet increased 5-HT2C expression
      while the lard diet reduced 5-HT1B mRNA. Ovariectomy increased the anxiety index,
      as derived from the elevated plus maze test, while both high-fat groups showed
      normalization of this index. In the forced swimming test, ovariectomy allied to
      high-lard diet, but not to fish-oil diet, reduced the latency to immobility,
      indicating vulnerability to a depressive-like state. Linear regression analysis
      showed hippocampal AgRP to be negatively associated with the anxiety index and
      hypothalamic AgRP to be positively associated with the latency to immobility.
      These AgRp gene expression associations are indicative of a beneficial
      involvement of this neuropeptide on both depression and anxiety measures. The
      present findings demonstrate metabolic, neurochemical and behavioral alterations
      after ovaries removal and highlight a positive effect of high-fat feeding on the
      anxiety-like behavior shown by ovariectomized animals. Since the polyunsaturated
      omega-3 intake (fish diet), unlike the saturated fat intake (lard diet), failed
      to induce deleterious metabolic or neurochemical consequences, further studies
      are needed focusing on the potential of this dietary component as an adjuvant
      anxiolytic agent after menopause.

PMID- 30233287
TI  - Genetic Deletion of PGF2alpha-FP Receptor Exacerbates Brain Injury Following
      Experimental Intracerebral Hemorrhage.
AB  - Background: The release of inflammatory molecules such as prostaglandins (e.g.,
      PGF2alpha) is associated with brain damage following an intracerebral hemorrhagic
      (ICH) stroke; however, the role of PGF2alpha and its cognate FP receptor in ICH
      remains unclear. This study focused on investigating the role of the FP receptor
      as a target for novel neuroprotective drugs in a preclinical model of ICH, aiming
      to investigate the contribution of the PGF2alpha-FP axis in modulating functional
      recovery and anatomical outcomes following ICH. Results: Neurological deficit
      scores in FP-/- mice were significantly higher compared to WT mice 72 h after ICH
      (6.1 +/- 0.7 vs. 3.1 +/- 0.8; P < 0.05). Assessing motor skills, the total time
      mice stayed on the rotating rod was significantly less in FP-/-mice compared to
      WT mice 24 h after ICH (27.0 +/- 7.5 vs. 52.4 +/- 11.2 s; P < 0.05). Using grip
      strength to quantify forepaw strength, results showed that the FP-/- mice had
      significantly less strength compared to WT mice 72 h after ICH (96.4 +/- 17.0 vs.
      129.6 +/- 5.9 g; P < 0.01). In addition to the behavioral outcomes,
      histopathological measurements were made. In Cresyl violet stained brain
      sections, the FP-/- mice showed a significantly larger lesion volume compared to
      the WT (15.0 +/- 2.2 vs. 3.2 +/- 1.7 mm3; P < 0.05 mice.) To estimate the
      presence of ferric iron in the peri-hematoma area, Perls' staining was performed,
      which revealed that FP-/- mice had significantly greater staining than the WT
      mice (186.3 +/- 34.4% vs. 86.9 +/- 13.0% total positive pixel counts, P < 0.05).
      Immunoreactivity experiments on brain sections from FP-/- and WT mice post-ICH
      were performed to monitor changes in microgliosis and astrogliosis using
      antibodies against Iba1 and GFAP respectively. These experiments showed that FP-/
      mice had a trend toward greater astrogliosis than WT mice post-ICH. Conclusion:
      We showed that deletion of the PGF2alpha FP receptor exacerbates behavioral
      impairments and increases lesion volumes following ICH compared to WT-matched
      controls.Detailed mechanisms responsible for these novel results are actively
      being pursued.

PMID- 30233296
TI  - Encoding Praise and Criticism During Social Evaluation Alters Interactive
      Responses in the Mentalizing and Affective Learning Networks.
AB  - Verbal communication with evaluative characters of different emotional valence
      has a considerable impact on the extent to which social relations are facilitated
      or undermined. Here using functional magnetic resonance imaging, we investigated
      how the brain acts in response to social praise and criticism, leading to
      differential affective judgments. We engaged thirty men and women in a task
      associating sex-balanced, neutral faces with praising or criticizing comments
      targeting others or objects. A whole-brain analysis revealed that criticism as
      compared to praise enhanced the activation in the medial prefrontal cortex
      (mPFC), particularly its dorsal portion, whereas the right amygdala displayed an
      opposite pattern of changes. Comments on others relative to objects increased the
      reactivity in the left posterior superior temporal sulcus and posterior cingulate
      cortex (PCC) such that both praise and criticism of others produced stronger
      activation in these two regions than their object-targeted counterparts. The
      interaction of valence and target was identified in the mPFC with greater
      reactivity in the contrasts of criticism vs. praise in the social context and
      others- vs. object-targeted criticism. Comments also modulated the functional
      connectivity of prior activated regions with the left temporoparietal junction,
      bilateral caudate and left PCC/precuneus showing reduced connectivity in response
      to social criticism but greatly strengthened connectivity for social praise as
      compared to non-social counterparts. These neural effects subsequently led to
      altered likeability ratings for the faces. Neither behavioral nor neural effects
      observed were influenced by the gender of participants. Taken together, our
      findings suggest a fundamental interactive role of the mentalizing and affective
      learning networks in differential encoding of individuals associated with
      praising or criticizing others, leading to learning of valenced traits and
      subsequent approach or avoidance responses in social interactions.

PMID- 30233293
TI  - Triglyceride Form of Docosahexaenoic Acid Mediates Neuroprotection in
      Experimental Parkinsonism.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder of unknown etiology. The
      main treatment of PD consists of medication with dopamine-based drugs, which
      palliate the symptoms but may produce adverse effects after chronic
      administration. Accordingly, there is a need to develop novel neuroprotective
      therapies. Several studies suggest that omega-3 polyunsaturated fatty acids (n-3
      PUFA) might provide protection against brain damage. Here, we studied several
      experimental models of PD, using striatal neuronal cultures, striatal slices, and
      mice, to assess the neuroprotective effects of docosahexaenoic acid (DHA), the
      main n-3 PUFA in the brain, administered in its triglyceride form (TG-DHA).
      Hence, we determined the beneficial effects of TG-DHA on neural viability
      following 6-hydroxydopamine (6-OHDA)-induced neurotoxicity, a well-established PD
      model. We also implemented a novel mouse behavioral test, the beam walking test,
      to finely assess mouse motor skills following dopaminergic denervation. This test
      showed potential as a useful behavioral tool to assess novel PD treatments. Our
      results indicated that TG-DHA-mediated neuroprotection was independent of the net
      incorporation of PUFA into the striatum, thus suggesting a tight control of brain
      lipid homeostasis both in normal and pathological conditions.

PMID- 30233292
TI  - A Novel Scoring System for Rupture Risk Stratification of Intracranial Aneurysms:
      A Hemodynamic and Morphological Study.
AB  - Objective: The aim of the present study is to investigate the potential
      morphological and hemodynamic risk factors related to intracranial aneurysms
      (IAs) rupture and establish a system to stratify the risk of IAs rupture to help
      the clinical decision-making. Methods: Patients admitted to our hospital for
      single-IAs were selected from January 2012 and January 2018. A propensity score
      matching was conducted to match patients. The morphological parameters were
      obtained from high solution CTA images, and the hemodynamic parameters were
      obtained in accordance with the outcomes of computational fluid dynamics (CFDs)
      simulation. Differences in the morphologic and hemodynamic parameters were
      compared. The significant parameters were selected to establish a novel scoring
      system (Intracranial Aneurysm Rupture Score, IARS). The comparison was drawn
      between the discriminating accuracy of IARS and the Rupture Resemblance Score
      (RRS) system to verify the value of IARS. Then, a group of patients with
      unruptured IAs was stratified into the high risk and low risk groups by IARS and
      RRS system separately and was followed up for 18-27 months to verify the value of
      IARS. The outcome of different stratifications was compared. Results: The
      matching process yielded 167 patients in each group. Differences of statistical
      significance were found in aneurysm length (p = 0.001), perpendicular height (H)
      (p < 0.001), aspect ratio (AR) (p < 0.001), size ratio (SR) (p < 0.001), deviated
      angle (DA) (p < 0.001), normalized average wall shear stress (NWSSa) (p < 0.001),
      wall shear stress gradient (WSSG) (p < 0.001), low shear area ratio (LSAR) (p =
      0.01), and oscillatory shear index (OSI) (p = 0.01). Logistic regression analysis
      further demonstrated that SR, DA, NWSSa, LSAR, and OSI were the independent risk
      factors of IAs rupture. SR, DA, LSAR, and OSI were finally selected to establish
      the IARS. Our present IARS showed a higher discriminating value (AUC 0.81 vs.
      0.77) in comparison with the RRS (SR, NWSSa, and OSI). After follow-up, seven
      patients were subject to IAs rupture. 5/26 in high risk group stratified by IARS,
      yet 7/57 in high risk group stratified by RRS. The accuracy of IARS was further
      verified (19.2% vs. 12.3%, AUC for the IARS and the RRS was 0.723 and 0.673,
      respectively). Conclusion: SR, DA, NWSSa, LSAR, and OSI were considered the
      independent risk factors of IAs rupture. Our novel IARS showed higher accuracy in
      discriminating IA rupture in comparison with RRS.

PMID- 30233294
TI  - Transcranial Direct Current Stimulation of the Right Lateral Prefrontal Cortex
      Changes a priori Normative Beliefs in Voluntary Cooperation.
AB  - A priori normative beliefs, the precondition of social norm compliance that
      reflects culture and values, are considered unique to human social behavior.
      Previous studies related to the ultimatum game revealed that right lateral
      prefrontal cortex (rLPFC) has no stimulation effects on normative beliefs.
      However, no research has focused on the effects of a priori belief on the rLPFC
      in voluntary cooperation attached to the public good (PG) game. In this study, we
      used a linear asymmetric PG to confirm the influence of the rLPFC on a priori
      normative beliefs without threats of external punishment through transcranial
      direct current stimulation (tDCS). Participants engaged via computer terminals in
      groups of four (i.e., two high-endowment players with 35G$ and two low-endowment
      players with 23G$). They were anonymous and had no communication during the
      entire process. They were randomly assigned to receive 15 min of either anodal,
      cathodal, or sham stimulation and then asked to answer questions concerning a
      priori normative beliefs (norm.belief and pg.belief). Results suggested that
      anodal/cathodal tDCS significantly (P < 0.001) shifted the participants' a priori
      normative beliefs in opposite directions compared to the shift in the sham group.
      In addition, different identities exhibited varying degrees of change (28.80
      54.43%). These outcomes provide neural evidence of the rLPFC mechanism's effect
      on the normative beliefs in voluntary cooperation based on the PG framework.

PMID- 30233289
TI  - Mobile Mechatronic/Robotic Orthotic Devices to Assist-Rehabilitate Neuromotor
      Impairments in the Upper Limb: A Systematic and Synthetic Review.
AB  - This paper overviews the state-of-the-art in upper limb robot-supported
      approaches, focusing on advancements in the related mechatronic devices for the
      patients' rehabilitation and/or assistance. Dedicated to the technical,
      comprehensively methodological and global effectiveness and improvement in this
      inter-disciplinary field of research, it includes information beyond the therapy
      administrated in clinical settings-but with no diminished safety requirements.
      Our systematic review, based on PRISMA guidelines, searched articles published
      between January 2001 and November 2017 from the following databases: Cochrane,
      Medline/PubMed, PMC, Elsevier, PEDro, and ISI Web of Knowledge/Science. Then we
      have applied a new innovative PEDro-inspired technique to classify the relevant
      articles. The article focuses on the main indications, current technologies,
      categories of intervention and outcome assessment modalities. It includes also,
      in tabular form, the main characteristics of the most relevant mobile (wearable
      and/or portable) mechatronic/robotic orthoses/exoskeletons prototype devices used
      to assist-rehabilitate neuromotor impairments in the upper limb.

PMID- 30233291
TI  - Quantitative EEG Tomography of Early Childhood Malnutrition.
AB  - The goal of this study is to identify the quantitative electroencephalographic
      (qEEG) signature of early childhood malnutrition [protein-energy malnutrition
      (PEM)]. To this end, archival digital EEG recordings of 108 participants in the
      Barbados Nutrition Study (BNS) were recovered and cleaned of artifacts (46
      children who suffered an episode of PEM limited to the first year of life) and 62
      healthy controls). The participants of the still ongoing BNS were initially
      enrolled in 1973, and EEGs for both groups were recorded in 1977-1978 (at 5-11
      years). Scalp and source EEG Z-spectra (to correct for age effects) were obtained
      by comparison with the normative Cuban Human Brain Mapping database. Differences
      between both groups in the z spectra (for all electrode locations and frequency
      bins) were assessed by t-tests with thresholds corrected for multiple comparisons
      by permutation tests. Four clusters of differences were found: (a) increased
      theta activity (3.91-5.86 Hz) in electrodes T4, O2, Pz and in the sources of the
      supplementary motor area (SMA); b) decreased alpha1 (8.59-8.98 Hz) in Fronto
      central electrodes and sources of widespread bilateral prefrontal are; (c)
      increased alpha2 (11.33-12.50 Hz) in Temporo-parietal electrodes as well as in
      sources in Central-parietal areas of the right hemisphere; and (d) increased beta
      (13.67-18.36 Hz), in T4, T5 and P4 electrodes and decreased in the sources of
      bilateral occipital-temporal areas. Multivariate Item Response Theory of EEGs
      scored visually by experts revealed a neurophysiological latent variable which
      indicated excessive paroxysmal and focal abnormality activity in the PEM group. A
      robust biomarker construction procedure based on elastic-net regressions and 1000
      cross-validations was used to: (i) select stable variables and (ii) calculate the
      area under ROC curves (AUC). Thus, qEEG differentiate between the two nutrition
      groups (PEM vs Control) performing as well as visual inspection of the EEG scored
      by experts (AUC = 0.83). Since PEM is a global public health problem with
      lifelong neurodevelopmental consequences, our finding of consistent differences
      between PEM and controls, both in qualitative and quantitative EEG analysis,
      suggest that this technology may be a source of scalable and affordable
      biomarkers for assessing the long-term brain impact of early PEM.

PMID- 30233290
TI  - In vitro Models for Seizure-Liability Testing Using Induced Pluripotent Stem
      Cells.
AB  - The brain is the most complex organ in the body, controlling our highest
      functions, as well as regulating myriad processes which incorporate the entire
      physiological system. The effects of prospective therapeutic entities on the
      brain and central nervous system (CNS) may potentially cause significant injury,
      hence, CNS toxicity testing forms part of the "core battery" of safety
      pharmacology studies. Drug-induced seizure is a major reason for compound
      attrition during drug development. Currently, the rat ex vivo hippocampal slice
      assay is the standard option for seizure-liability studies, followed by primary
      rodent cultures. These models can respond to diverse agents and predict seizure
      outcome, yet controversy over the relevance, efficacy, and cost of these animal
      based methods has led to interest in the development of human-derived models.
      Existing platforms often utilize rodents, and so lack human receptors and other
      drug targets, which may produce misleading data, with difficulties in inter
      species extrapolation. Current electrophysiological approaches are typically used
      in a low-throughput capacity and network function may be overlooked. Human
      derived induced pluripotent stem cells (iPSCs) are a promising avenue for
      neurotoxicity testing, increasingly utilized in drug screening and disease
      modeling. Furthermore, the combination of iPSC-derived models with functional
      techniques such as multi-electrode array (MEA) analysis can provide information
      on neuronal network function, with increased sensitivity to neurotoxic effects
      which disrupt different pathways. The use of an in vitro human iPSC-derived
      neural model for neurotoxicity studies, combined with high-throughput techniques
      such as MEA recordings, could be a suitable addition to existing pre-clinical
      seizure-liability testing strategies.

PMID- 30233298
TI  - Prenatal Deltamethrin Exposure-Induced Cognitive Impairment in Offspring Is
      Ameliorated by Memantine Through NMDAR/BDNF Signaling in Hippocampus.
AB  - Background: Pyrethroids have been widely used in residential and agricultural
      areas. However, little is known about the effects of prenatal exposure to
      deltamethrin on cognition in early development of offspring. In this study, the
      effects of prenatal exposure to deltamethrin on learning and memory abilities, N
      methyl-D-aspartate receptor (NMDAR) subunits, brain derived neurotrophic factor
      (BDNF), Tyrosine kinase B (TrkB) receptor, and phosphorylated cAMP response
      element binding protein (pCREB) in the hippocampus of offspring rats were
      investigated. Experimental Approaches: Groups each of six female SD rats, as F0
      generation, were administered with deltamethrin (0, 0.54, 1.35, and 2.7, 9
      mg/kg), or memantine (10 mg/kg), or co-administered with deltamethrin (9 mg/kg)
      and memantine (10 mg/kg) daily by gavage during pregnancy. The learning and
      memory ability was evaluated using Morris water maze (MWM) task on postnatal day
      21. The expression of NMDAR (GluN1, GluN2A, and GluN2B), BDNF, pTrkB/TrkB, and
      pCREB/CREB in hippocampus were assessed with western blotting. Results: Prenatal
      exposure to a relatively low dose of deltamethrin (2.7, 1.35, and 0.54 mg/kg) had
      no impact on learning and memory abilities or the expression of NMDAR, BDNF,
      pTrkB, and pCREB in the hippocampus of the exposed offspring. The group treated
      with 9 mg/kg deltamethrin showed impaired cognitive abilities and decreased
      expression levels of GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and pTrkB/TrkB in
      the hippocampus. However, the declined cognitive ability were ameliorated by
      memantine treatment with increased GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and
      pTrkB/TrkB expression in the hippocampus. Conclusion and Implications: Prenatal
      exposure to a relatively high does of deltamethrin (9 mg/kg) alters cognition in
      offsprings and that this cognitive dysfunction can be ameliorated by memantine
      treatment. Moreover, NMDAR/BDNF signaling may be associated with the effects of
      prenatal exposure to deltamethrin on cognitive ability in offspring.

PMID- 30233299
TI  - Partial Least Square Aided Beamforming Algorithm in Magnetoencephalography Source
      Imaging.
AB  - Beamforming techniques have played a prominent role in source imaging in
      neuroimaging and in locating epileptogenic zones. However, existing vector
      beamformers are sensitive to noise on localization of epileptogenic zones. In
      this study, partial least square (PLS) was used to aid the minimum variance
      beamforming approach for source imaging with magnetoencephalography (MEG) arrays,
      and verified its effectiveness in simulated data and epilepsy data. First, PLS
      was employed to extract the components of the MEG arrays by maximizing the
      covariance between a linear combination of the predictors and the class variable.
      Noise was then removed by reconstructing the MEG arrays based on those
      components. The minimum variance beamforming method was used to estimate a source
      model. Simulations with a realistic head model and varying noise levels indicated
      that the proposed approach can provide higher spatial accuracy than other well
      known beamforming methods. For real MEG recordings in 10 patients with temporal
      lobe epilepsy, the ratios of the number of spikes localized in the surgical
      excised region to the total number of spikes using the proposed method were
      higher than that of the dipole fitting method. These localization results using
      the proposed method are more consistent with the clinical evaluation. The
      proposed method may provide a new imaging marker for localization of
      epileptogenic zones.

PMID- 30233301
TI  - The Abnormality of Topological Asymmetry in Hemispheric Brain Anatomical Networks
      in Bipolar Disorder.
AB  - Convergent evidences have demonstrated a variety of regional abnormalities of
      asymmetry in bipolar disorder (BD). However, little is known about the
      alterations in hemispheric topological asymmetries. In this study, we used
      diffusion tensor imaging to construct the hemispheric brain anatomical network of
      49 patients with BD and 61 matched normal controls. Graph theory was then applied
      to quantify topological properties of the hemispheric networks. Although small
      world properties were preserved in the hemispheric networks of BD, the degrees of
      the asymmetry in global efficiency, characteristic path length, and small-world
      property were significantly decreased. More changes in topological properties of
      the right hemisphere than those of left hemisphere were found in patients
      compared with normal controls. Consistent with such changes, the nodal efficiency
      in patients with BD also showed less rightward asymmetry mainly in the frontal,
      occipital, parietal, and temporal lobes. In contrast to leftward asymmetry,
      significant rightward asymmetry was found in supplementary motor area of BD, and
      attributed to more deficits in nodal efficiency of the left hemisphere. Finally,
      these asymmetry score of nodal efficiency in the inferior parietal lobule and
      rolandic operculum were significantly associated with symptom severity of BD. Our
      results suggested that abnormal hemispheric asymmetries in brain anatomical
      networks were associated with aberrant neurodevelopment, and providing insights
      into the potential neural biomarkers of BD by measuring the topological asymmetry
      in hemispheric brain anatomical networks.

PMID- 30233300
TI  - No Evidence That Frontal Eye Field tDCS Affects Latency or Accuracy of
      Prosaccades.
AB  - Transcranial direct current stimulation (tDCS) may be used to directly affect
      neural activity from outside of the skull. However, its exact physiological
      mechanisms remain elusive, particularly when applied to new brain areas. The
      frontal eye field (FEF) has rarely been targeted with tDCS, even though it plays
      a crucial role in control of overt and covert spatial attention. Here, we
      investigate whether tDCS over the FEF can affect the latency and accuracy of
      saccadic eye movements. Twenty-six participants performed a prosaccade task in
      which they made eye movements to a sudden-onset eccentric visual target (lateral
      saccades). After each lateral saccade, they made an eye movement back to the
      center (center saccades). The task was administered before, during, and after
      anodal or cathodal tDCS over the FEF, in a randomized, double-blind, within
      subject design. One previous study (Kanai et al., 2012) found that anodal tDCS
      over the FEF decreased the latency of saccades contralateral to the stimulated
      hemisphere. We did not find the same effect: neither anodal nor cathodal tDCS
      influenced the latency of lateral saccades. tDCS also did not affect accuracy of
      lateral saccades (saccade endpoint deviation and saccade endpoint variability).
      For center saccades, we found some differences between the anodal and cathodal
      sessions, but these were not consistent across analyses (latency, endpoint
      variability), or were already present before tDCS onset (endpoint deviation). We
      tried to improve on the design of Kanai et al. (2012) in several ways, including
      the tDCS duration and electrode montage, which could explain the discrepant
      results. Our findings add to a growing number of null results, which have sparked
      concerns that tDCS outcomes are highly variable. Future studies should aim to
      establish the boundary conditions for FEF-tDCS to be effective, in addition to
      increasing sample size and adding additional controls such as a sham condition.
      At present, we conclude that it is unclear whether eye movements or other aspects
      of spatial attention can be affected through tDCS of the frontal eye fields.

PMID- 30233297
TI  - Nucleus Basalis of Meynert Stimulation for Dementia: Theoretical and Technical
      Considerations.
AB  - Deep brain stimulation (DBS) of nucleus basalis of Meynert (NBM) is currently
      being evaluated as a potential therapy to improve memory and overall cognitive
      function in dementia. Although, the animal literature has demonstrated robust
      improvement in cognitive functions, phase 1 trial results in humans have not been
      as clear-cut. We hypothesize that this may reflect differences in electrode
      location within the NBM, type and timing of stimulation, and the lack of a
      biomarker for determining the stimulation's effectiveness in real time. In this
      article, we propose a methodology to address these issues in an effort to
      effectively interface with this powerful cognitive nucleus for the treatment of
      dementia. Specifically, we propose the use of diffusion tensor imaging to
      identify the nucleus and its tracts, quantitative electroencephalography (QEEG)
      to identify the physiologic response to stimulation during programming, and
      investigation of stimulation parameters that incorporate the phase locking and
      cross frequency coupling of gamma and slower oscillations characteristic of the
      NBM's innate physiology. We propose that modulating the baseline gamma burst
      stimulation frequency, specifically with a slower rhythm such as theta or delta
      will pose more effective coupling between NBM and different cortical regions
      involved in many learning processes.

PMID- 30233304
TI  - Circulating miRNAs as Diagnostic Biomarkers for Parkinson's Disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      worldwide. Its main neuropathological hallmarks are the degeneration of
      dopaminergic neurons in the substantia nigra and alpha-synuclein containing
      protein inclusions, called Lewy Bodies. The diagnosis of idiopathic PD is still
      based on the assessment of clinical criteria, leading to an insufficient
      diagnostic accuracy. Additionally, there is no biomarker available allowing the
      prediction of the disease course or monitoring the response to therapeutic
      approaches. So far, protein biomarker candidates such as alpha-synuclein have
      failed to improve diagnosis of PD. Circulating microRNAs (miRNAs) in body fluids
      are promising biomarker candidates for PD, as they are easily accessible by non-
      or minimally-invasive procedures and changes in their expression are associated
      with pathophysiological processes relevant for PD. Advances in miRNA analysis
      methods resulted in numerous recent publications on miRNAs as putative
      biomarkers. Here, we discuss the applicability of different body fluids as
      sources for miRNA biomarkers, highlight technical aspects of miRNA analysis and
      give an overview on published studies investigating circulating miRNAs as
      biomarker candidates for diagnosis of PD and other Parkinsonian syndromes.

PMID- 30233306
TI  - Integrated Analysis Reveals Altered Lipid and Glucose Metabolism and Identifies
      NOTCH2 as a Biomarker for Parkinson's Disease Related Depression.
AB  - Depression is a common comorbidity in Parkinson's disease (PD) but is
      underdiagnosed. We aim to investigate the altered metabolic pathways of
      Parkinson's disease-related depression (PDD) in plasma and to identify potential
      biomarkers for clinical diagnosis. Consecutive patients with PD were recruited,
      clinically assessed, and patients with PDD identified. Fasting plasma samples
      were collected from 99 patients and differentially expressed metabolites and
      proteins between patients with PDD and PD were identified using non-targeted
      liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem
      mass tag (TMT)-based proteomics analysis, followed by an integrated analysis.
      Based on the above results, enzyme-linked immune sorbent assay (ELISA) tests were
      then performed to identify potential biomarkers for PDD. In clinics, patients
      with PDD suffered less hypertension and had lower serum low-density lipoprotein
      cholesterol and apolipoprotein B levels when compared to the other patients with
      PD. A total of 85 differentially expressed metabolites were identified in
      metabolomics analysis. These metabolites were mainly lipids and lipid-like
      molecules, involved in lipid and glucose metabolic pathways. According to
      proteomics analysis, 17 differentially expressed proteins were identified, and 12
      metabolic pathways were enriched, which were predominantly related to glucose
      metabolism. Integrated analysis indicated that altered lipid and glucose
      metabolism in PDD may induce cellular injury through oxidative stress.
      Additionally, plasma levels of several proteins were confirmed to be
      significantly altered and correlated with depressive severity. NOTCH2 may be a
      potential blood biomarker for PDD, with an optimal cut-off point of 0.91 ng/ml, a
      sensitivity value of 95.65%, and a specificity value of 81.58%. Depressive
      symptoms are associated with lipid and glucose metabolism in patients with PD and
      NOTCH2 may be a potential blood biomarker for the clinical diagnosis of PDD.

PMID- 30233311
TI  - Inflammasome Proteins in Serum and Serum-Derived Extracellular Vesicles as
      Biomarkers of Stroke.
AB  - The inflammasome is a key contributor to the inflammatory innate immune response
      after stroke. We have previously shown that inflammasome proteins are released in
      extracellular vesicles (EV) after brain and spinal cord injury. In addition, we
      have shown that inflammasome proteins offer great promise as biomarkers of
      central nervous system (CNS) injury following brain trauma. In the present study,
      we used a Simple Plex Assay (Protein Simple), a novel multi-analyte automated
      microfluidic immunoassay platform, to analyze serum and serum-derived EV samples
      from stroke patients and control subjects for inflammasome protein levels of
      caspase-1, apoptosis-associated speck-like protein containing a caspase
      recruitment domain (ASC), Interleukins (IL)-1beta, and (IL)-18. Receiver operator
      characteristic (ROC) curves with associated confidence intervals obtained from
      the analysis of serum samples revealed that the area under the curve (AUC) for
      ASC was 0.99 with a confidence interval between 0.9914 and 1.004, whereas the AUC
      for caspase-1, IL-1beta, and IL-18 were 0.75, 0.61, and 0.67, respectively. Thus,
      these data indicate that ASC is a potential biomarker of stroke and highlight the
      role of the inflammasome in the inflammatory response after brain ischemia.

PMID- 30233305
TI  - Integrative Brain Transcriptome Analysis Reveals Region-Specific and Broad
      Molecular Changes in Shank3-Overexpressing Mice.
AB  - Variants of the SH3 and multiple ankyrin repeat domain 3 (SHANK3) gene, encoding
      excitatory postsynaptic core scaffolding proteins, are causally associated with
      numerous neurodevelopmental and neuropsychiatric disorders, including autism
      spectrum disorder (ASD), bipolar disorder, intellectual disability, and
      schizophrenia (SCZ). Although detailed synaptic changes of various Shank3 mutant
      mice have been well characterized, broader downstream molecular changes,
      including direct and indirect changes, remain largely unknown. To address this
      issue, we performed a transcriptome analysis of the medial prefrontal cortex
      (mPFC) of adult Shank3-overexpressing transgenic (TG) mice, using an RNA
      sequencing approach. We also re-analyzed previously reported RNA-sequencing
      results of the striatum of adult Shank3 TG mice and of the prefrontal cortex of
      juvenile Shank3+/DeltaC mice with a 50-70% reduction of Shank3 proteins. We found
      that several myelin-related genes were significantly downregulated specifically
      in the mPFC, but not in the striatum or hippocampus, of adult Shank3 TG mice by
      comparing the differentially expressed genes (DEGs) of the analyses side by side.
      Moreover, we also found nine common DEGs between the mPFC and striatum of Shank3
      TG mice, among which we further characterized ASD- and SCZ-associated G protein
      coupled receptor 85 (Gpr85), encoding an orphan Gpr interacting with PSD-95.
      Unlike the mPFC-specific decrease of myelin-related genes, we found that the mRNA
      levels of Gpr85 increased in multiple brain regions of adult Shank3 TG mice,
      whereas the mRNA levels of its family members, Gpr27 and Gpr173, decreased in the
      cortex and striatum. Intriguingly, in cultured neurons, the mRNA levels of Gpr27,
      Gpr85, and Gpr173 were modulated by the neuronal activity. Furthermore,
      exogenously expressed GPR85 was co-localized with PSD-95 and Shank3 in cultured
      neurons and negatively regulated the number of excitatory synapses, suggesting
      its potential role in homeostatic regulation of excitatory synapses in Shank3 TG
      neurons. Finally, we performed a gene set enrichment analysis of the RNA
      sequencing results, which suggested that Shank3 could affect the directional
      expression pattern of numerous ribosome-related genes in a dosage-dependent
      manner. To sum up, these results reveal previously unidentified brain region
      specific and broad molecular changes in Shank3-overexpressing mice, further
      elucidating the complexity of the molecular pathophysiology of SHANK3-associated
      brain disorders.

PMID- 30233302
TI  - Prefrontal Cortex Activity Predicts Mental Fatigue in Young and Elderly Men
      During a 2 h "Go/NoGo" Task.
AB  - Background: Although the effects of mental fatigue on cognitive-motor function
      and psychological state in young adults are well-documented, its effects in the
      elderly are not completely understood. The aim of this study was to estimate the
      effect of prolonged cognitive load on the indicators of psychological, cognitive,
      and motor functions. Methods: Fifteen young and 15 elderly men were asked to
      perform a 2 h "Go/NoGo" task. Psychological state (mood and motivation),
      cognitive (prefrontal cortex activity and cognitive performance), and motor
      (motor cortex excitability and grip strength) functions were measured before and
      after the task. During the 2 h task, both groups had a significantly similar
      increase in the number of "Incorrect NoGo" errors. Only in young men reaction
      time (RT) of "Incorrect NoGo" and intraindividual variability of RT of "Incorrect
      NoGo" significantly increased during task. After the task, handgrip strength
      decreased for the young men, whereas latency of motor evoked potentials prolonged
      both groups. Nevertheless, both groups indicated that they felt fatigue after the
      2 h task; we observed that mental demand increased, whereas intrinsic motivation
      and mood decreased only in young men. Prolonged task decreased the switching/rest
      ratio of oxygenated hemoglobin for the young and the elderly men; however,
      greater for elderly than young men. Interestingly, the more the prefrontal cortex
      was activated before the 2 h task during the switching task, the fewer of
      "Incorrect NoGo" errors made by the young men and the greater the number of
      errors made by the elderly men. Conclusion: Because of the greater mental load
      and (possibly) greater activation of prefrontal cortex during the 2 h "Go/NoGo"
      task, there was greater mental and neuromuscular performance fatigue in young men
      than in elderly men.

PMID- 30233308
TI  - Antagonistic Effect of a Cytoplasmic Domain on the Basal Activity of Polymodal
      Potassium Channels.
AB  - TREK/TRAAK channels are polymodal K+ channels that convert very diverse stimuli,
      including bioactive lipids, mechanical stretch and temperature, into electrical
      signals. The nature of the structural changes that regulate their activity
      remains an open question. Here, we show that a cytoplasmic domain (the proximal C
      ter domain, pCt) exerts antagonistic effects in TREK1 and TRAAK. In basal
      conditions, pCt favors activity in TREK1 whereas it impairs TRAAK activity. Using
      the conformation-dependent binding of fluoxetine, we show that TREK1 and TRAAK
      conformations at rest are different, and under the influence of pCt. Finally, we
      show that depleting PIP2 in live cells has a more pronounced inhibitory effect on
      TREK1 than on TRAAK. This differential regulation of TREK1 and TRAAK is related
      to a previously unrecognized PIP2-binding site (R329, R330, and R331) present
      within TREK1 pCt, but not in TRAAK pCt. Collectively, these new data point out
      pCt as a major regulatory domain of these channels and suggest that the binding
      of PIP2 to the pCt of TREK1 results in the stabilization of the conductive
      conformation in basal conditions.

PMID- 30233309
TI  - Modeling of Zinc Dynamics in the Synaptic Cleft: Implications for Cadherin
      Mediated Adhesion and Synaptic Plasticity.
AB  - While the numerous influences of synaptically released zinc on synaptic
      efficiency during long-term potentiation have been discussed by many authors
      already, we focused on the possible effect of zinc on cadherins and therefore its
      contribution to morphological changes in the context of synaptic plasticity. The
      difficulty with gaining insights into the dynamics of zinc-cadherin interaction
      is the inability to directly observe it on a suitable timescale. Therefore our
      approach was to establish an analytical model of the zinc diffusion dynamics in
      the synaptic cleft and experimentally validate, if the theoretical concentrations
      at the periphery of the synaptic cleft are sufficient to significantly modulate
      cadherin-mediated adhesion. Our results emphasize, that synaptically released
      zinc might have a strong accelerating effect on the morphological changes
      involved in long-term synaptic plasticity. The approach presented here might also
      prove useful for investigations on other synaptically released trace metals.

PMID- 30233303
TI  - Quality Over Quantity: Advantages of Using Alpha-Synuclein Preformed Fibril
      Triggered Synucleinopathy to Model Idiopathic Parkinson's Disease.
AB  - Animal models have significantly advanced our understanding of Parkinson's
      disease (PD). Alpha-synuclein (alpha-syn) has taken center stage due to its
      genetic connection to familial PD and localization to Lewy bodies, one
      pathological hallmark of PD. Animal models developed on the premise of elevated
      alpha-synuclein via germline manipulation or viral vector-mediated overexpression
      are used to investigate PD pathophysiology and vet novel therapeutics. While
      these models represented a step forward compared to their neurotoxicant model
      predecessors, they rely on overexpression of supraphysiological levels of alpha
      syn to trigger toxicity. However, whereas SNCA-linked familial PD is associated
      with elevated alpha-syn, elevated alpha-syn is not associated with idiopathic PD.
      Therefore, the defining feature of the alpha-syn overexpression models may fail
      to appropriately model idiopathic PD. In the last several years a new model has
      been developed in which alpha-syn preformed fibrils are injected intrastriatally
      and trigger normal endogenous levels of alpha-syn to misfold and accumulate into
      Lewy body-like inclusions. Following a defined period of inclusion accumulation,
      distinct phases of neuroinflammation and progressive degeneration can be detected
      in the nigrostriatal system. In this perspective, we highlight the fact that
      levels of alpha-syn achieved in overexpression models generally exceed those
      observed in idiopathic and even SNCA multiplication-linked PD. This raises the
      possibility that supraphysiological alpha-syn expression may drive
      pathophysiological mechanisms not relevant to idiopathic PD. We argue in this
      perspective that synucleinopathy triggered to form within the context of normal
      alpha-syn expression represents a more faithful animal model of idiopathic PD
      when examining the role of neuroinflammation or the relationship between a-syn
      aggregation and toxicity.

PMID- 30233316
TI  - Commentary: GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in
      Mice: Role of Hippocampal NR2B and DISC1.

PMID- 30233314
TI  - Lack of the Actin Capping Protein, Eps8, Affects NMDA-Type Glutamate Receptor
      Function and Composition.
AB  - Actin-based remodeling underlines spine morphogenesis and plasticity and is
      crucially involved in the processes that constantly reshape the circuitry of the
      adult brain in response to external stimuli, leading to learning and memory
      formation and supporting cognitive functions. Hence spine morphology and synaptic
      strength are tightly linked and indeed abnormalities in spine number and
      morphology have been described in a number of neurological disorders such as
      autism spectrum disorders (ASDs), schizophrenia and intellectual disabilities. We
      have recently demonstrated that the actin regulating protein, Epidermal growth
      factor receptor pathway substrate 8 (Eps8), is essential for spine growth and
      long term potentiation. Indeed, mice lacking Eps8 display immature filopodia-like
      spines, which are unable to undergo potentiation, and are impaired in cognitive
      functions. Furthermore, reduced levels of Eps8 have been found in the brain of a
      cohort of patients affected by ASD compared to controls. Here we investigated
      whether the lack of Eps8, which is also part of the N-methyl-d-aspartate (NMDA)
      receptor complex, affects the functional maturation of the postsynaptic
      compartment. Our results demonstrate that Eps8 knock out mice (Eps8 KO) neurons
      display altered synaptic expression and subunit composition of NMDA receptors
      (i.e., increased GluN2B-, decreased GluN2A-containing receptors) and impaired
      GluN2B to GluN2A subunit shift. Indeed Eps8 KO neurons display increased content
      of GluN2B containing NMDA receptors both at the synaptic and extrasynaptic level.
      Furthermore, Eps8 KO neurons display an increased content of extra-synaptic
      GluN2B-containing receptors, suggesting that also the synaptic targeting of NMDA
      receptors is affected by the lack of Eps8. These data demonstrate that, besides
      regulation of spine morphogenesis, Eps8 also regulates the synaptic balance of
      NMDA receptors subunits GluN2A and GluN2B.

PMID- 30233313
TI  - A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability,
      Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus.
AB  - The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in
      which neurogenesis is maintained throughout adulthood. It is believed that
      newborn neurons in this region encode temporal information about partially
      overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT)
      is a naturally occurring compound capable of inducing a powerful psychedelic
      state. Recently, it has been suggested that DMT analogs may be used in the
      treatment of mood disorders. Due to the strong link between altered neurogenesis
      and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell
      proliferation. We show that a single intracerebroventricular (ICV) injection of 5
      MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG.
      Moreover, using a transgenic animal expressing tamoxifen-dependent Cre
      recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had
      a higher number of newborn DG Granule cells (GC). We also showed that these DG GC
      have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC
      treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials
      and higher action potential (AP) threshold compared. Our findings show that 5-MeO
      DMT affects neurogenesis and this effect may contribute to the known
      antidepressant properties of DMT-derived compounds.

PMID- 30233312
TI  - Localization of RNAi Machinery to Axonal Branch Points and Growth Cones Is
      Facilitated by Mitochondria and Is Disrupted in ALS.
AB  - Local protein synthesis in neuronal axons plays an important role in essential
      spatiotemporal signaling processes; however, the molecular basis for the post
      transcriptional regulation controlling this process in axons is still not fully
      understood. Here we studied the axonal mechanisms underlying the transport and
      localization of microRNA (miRNA) and the RNAi machinery along the axon. We first
      identified miRNAs, Dicer, and Argonaute-2 (Ago2) in motor neuron (MN) axons. We
      then studied the localization of RNAi machinery and demonstrated that
      mitochondria associate with miR-124 and RNAi proteins in axons. Importantly, this
      co-localization occurs primarily at axonal branch points and growth cones.
      Moreover, using live cell imaging of a functional Cy3-tagged miR-124, we revealed
      that this miRNA is actively transported with acidic compartments in axons, and
      associates with stalled mitochondria at growth cones and axonal branch points.
      Finally, we observed enhanced retrograde transport of miR-124-Cy3, and a
      reduction in its localization to static mitochondria in MNs expressing the ALS
      causative gene hSOD1G93A. Taken together, our data suggest that mitochondria
      participate in the axonal localization and transport of RNAi machinery, and
      further imply that alterations in this mechanism may be associated with
      neurodegeneration in ALS.

PMID- 30233318
TI  - The Regulation of Axon Diameter: From Axonal Circumferential Contractility to
      Activity-Dependent Axon Swelling.
AB  - In the adult nervous system axon caliber varies widely amongst different tracts.
      When considering a given axon, its diameter can further fluctuate in space and
      time, according to processes including the distribution of organelles and
      activity-dependent mechanisms. In addition, evidence is emerging supporting that
      in axons circumferential tension/contractility is present. Axonal diameter is
      generically regarded as being regulated by neurofilaments. When neurofilaments
      are absent or low, microtubule-dependent mechanisms can also contribute to the
      regulation of axon caliber. Despite this knowledge, the fine-tune mechanisms
      controlling diameter and circumferential tension throughout the lifetime of an
      axon, remain largely elusive. Recent data supports the role of the actin-spectrin
      based membrane periodic skeleton and of non-muscle myosin II in the control of
      axon diameter. However, the cytoskeletal arrangement that underlies
      circumferential axonal contraction and expansion is still to be discovered. Here,
      we discuss in a critical viewpoint the existing knowledge on the regulation of
      axon diameter, with a specific focus on the possible role played by the axonal
      actin cytoskeleton.

PMID- 30233315
TI  - Alanine Scanning Mutagenesis of the C-Terminal Cytosolic End of Gpm6a Identifies
      Key Residues Essential for the Formation of Filopodia.
AB  - Neuronal membrane glycoprotein M6a (Gpm6a) is a protein with four transmembrane
      regions and the N- and the C-ends facing the cytosol. It functions in processes
      of neuronal development, outgrowth of neurites, and formation of filopodia,
      spines, and synapsis. Molecular mechanisms by which Gpm6a acts in these processes
      are not fully comprehended. Structural similarities of Gpm6a with tetraspanins
      led us to hypothesize that, similarly to tetraspanins, the cytoplasmic tails
      function as connections with cytoskeletal and/or signaling proteins. Here, we
      demonstrate that the C- but not the N-terminal cytosolic end of Gpm6a is required
      for the formation of filopodia by Gpm6a in cultured neurons from rat hippocampus
      and in neuroblastoma cells N2a. Further immunofluorescence microcopy and flow
      cytometry analysis show that deletion of neither the N- nor the C-terminal
      intracellular domains interferes with the recognition of Gpm6a by the function
      blocking antibody directed against the extracellular part of Gpm6a. Expression
      levels of both truncation mutants were not affected but we observed decrease in
      the amount of both truncated proteins on cell surface suggesting that the
      incapacity of the Gpm6a lacking C-terminus to induce filopodium formation is not
      due to the lower amount of Gpm6a on cell surface. Following colocalization assays
      shows that deletion of the C- but not the N-terminus diminishes the association
      of Gpm6a with clathrin implying involvement of clathrin-mediated trafficking
      events. Next, using comprehensive alanine scanning mutagenesis of the C-terminus
      we identify K250, K255, and E258 as the key residues for the formation of
      filopodia by Gpm6a. Substitution of these charged residues with alanine also
      diminishes the amount of Gpm6a on cell surface and in case of K255 and E258 leads
      to the lower amount of total expressed protein. Subsequent bioinformatic analysis
      of Gpm6a amino acid sequence reveals that highly conserved and functional
      residues cluster preferentially within the C- and not within the N-terminus and
      that K250, K255, and E258 are predicted as part of sorting signals of
      transmembrane proteins. Altogether, our results provide evidence that filopodium
      outgrowth induced by Gpm6a requires functionally critical residues within the C
      terminal cytoplasmic tail.

PMID- 30233307
TI  - N-Methyl-D-Aspartate Receptor Link to the MAP Kinase Pathway in Cortical and
      Hippocampal Neurons and Microglia Is Dependent on Calcium Sensors and Is Blocked
      by alpha-Synuclein, Tau, and Phospho-Tau in Non-transgenic and Transgenic
      APPSw,Ind Mice.
AB  - N-methyl-D-aspartate receptors (NMDARs) respond to glutamate to allow the influx
      of calcium ions and the signaling to the mitogen-activated protein kinase (MAPK)
      cascade. Both MAPK- and Ca2+-mediated events are important for both
      neurotransmission and neural cell function and fate. Using a heterologous
      expression system, we demonstrate that NMDAR may interact with the EF-hand
      calcium-binding proteins calmodulin, calneuron-1, and NCS1 but not with
      caldendrin. NMDARs were present in primary cultures of both neurons and microglia
      from cortex and hippocampus. Calmodulin in microglia, and calmodulin and NCS1 in
      neurons, are necessary for NMDA-induced MAP kinase pathway activation.
      Remarkably, signaling to the MAP kinase pathway was blunted in primary cultures
      of cortical and hippocampal neurons and microglia from wild-type animals by
      proteins involved in neurodegenerative diseases: alpha-synuclein, Tau, and p-Tau.
      A similar blockade by pathogenic proteins was found using samples from the
      APPSw,Ind transgenic Alzheimer's disease model. Interestingly, a very marked
      increase in NMDAR-NCS1 complexes was identified in neurons and a marked increase
      of both NMDAR-NCS1 and NMDAR-CaM complexes was identified in microglia from the
      transgenic mice. The results show that alpha-synuclein, Tau, and p-Tau disrupt
      the signaling of NMDAR to the MAPK pathway and that calcium sensors are important
      for NMDAR function both in neurons and microglia. Finally, it should be noted
      that the expression of receptor-calcium sensor complexes, specially those
      involving NCS1, is altered in neural cells from APPSw,Ind mouse embryos/pups.

PMID- 30233325
TI  - Current Source Density Analysis of Electroantennogram Recordings: A Tool for
      Mapping the Olfactory Response in an Insect Antenna.
AB  - The set of chemosensory receptors expressed by the olfactory receptor neurons
      lying in an insect's antennae and maxillary palps define the ability of this
      insect to perceive the volatile chemicals of its environment. The main two
      electrophysiological methods of antennal recordings for studying the range of
      chemicals that activate chemosensory receptors have limitations. Single-sensillum
      recording (SSR) samples a subset of olfactory receptor neurons and therefore does
      not reveal the full capacity of an insect to perceive an odor.
      Electroantennography (EAG), even if less resolutive than SSRs, is sometimes
      preferred since it samples the activity of a large number of the olfactory
      receptor neurons. But, at least in flies, the amplitude of the EAG signal is not
      directly correlated with the degree of sensitivity of the insect to the olfactory
      compound. Such dual methodology was also used to study mammalian brains, and the
      current source density (CSD) analysis was developed to bridge the gap between the
      cellular and the population recordings. This paper details the use of a similar
      approach adapted to the study of olfactory responses within insects with bulbous
      antennae. The EAG was recorded at multiple antennal positions and the CSD that
      generates the EAG potentials were estimated. The method measures the activation
      of olfactory receptor neurons (ORNs) across the antennae and thus it quantifies
      the olfactory sensitivity of the insect. It allows a rapid mapping of olfactory
      responses and thus can be used to guide further SSRs or to determine that two
      chemicals are detected by independent ORNs. This study further explored biases
      resulting from a limited number of recording positions or from an approximation
      of the antennal geometry that should be considered for interpreting the CSD maps.
      It also shows that the CSD analysis of EAGs is compatible with a gas
      chromatograph stimulator for analyzing the response to complex odors. Finally, I
      discuss the origin of the EAG signal in light of the CSD theory.

PMID- 30233322
TI  - GSK-3beta Inhibitor Alsterpaullone Attenuates MPP+-Induced Cell Damage in a c-Myc
      Dependent Manner in SH-SY5Y Cells.
AB  - Mitochondrial dysfunction plays significant roles in the pathogenesis of
      Parkinson's Disease (PD). The inactivation of c-Myc, a down-stream gene of
      Wnt/beta-catenin signaling, may contribute to the mitochondria dysfunction.
      Inhibition of glycogen synthase kinase 3beta (GSK-3beta) with Alsterpaullone
      (Als) can activate the down-stream events of Wnt signaling. Here, we investigated
      the protective roles of Als against MPP+-induced cell apoptosis in SH-SY5Y cells.
      The data showed that Als effectively rescued c-Myc from the MPP+-induced decline
      via Wnt signaling. Furthermore, Als protected SH-SY5Y cells from the MPP+-induced
      mitochondrial fission and cell apoptosis. However, the protective roles of Als
      were lost under beta-catenin-deficient conditions. These findings indicate that
      Als, a GSK-3beta inhibitor, attenuated the MPP+-induced mitochondria-dependent
      apoptotic via up-regulation of the Wnt signaling.

PMID- 30233310
TI  - Pharmacological c-Jun NH2-Terminal Kinase (JNK) Pathway Inhibition Reduces
      Severity of Spinal Muscular Atrophy Disease in Mice.
AB  - Spinal muscular atrophy (SMA) is a severe neurodegenerative disorder that occurs
      in early childhood. The disease is caused by the deletion/mutation of the
      survival motor neuron 1 (SMN1) gene resulting in progressive skeletal muscle
      atrophy and paralysis, due to the degeneration of spinal motor neurons (MNs).
      Currently, the cellular and molecular mechanisms underlying MN death are only
      partly known, although recently it has been shown that the c-Jun NH2-terminal
      kinase (JNK)-signaling pathway might be involved in the SMA pathogenesis. After
      confirming the activation of JNK in our SMA mouse model (SMN2+/+; SMNDelta7+/+;
      Smn-/-), we tested a specific JNK-inhibitor peptide (D-JNKI1) on these mice, by
      chronic administration from postnatal day 1 to 10, and histologically analyzed
      the spinal cord and quadriceps muscle at age P12. We observed that D-JNKI1
      administration delayed MN death and decreased inflammation in spinal cord.
      Moreover, the inhibition of JNK pathway improved the trophism of SMA muscular
      fibers and the size of the neuromuscular junctions (NMJs), leading to an
      ameliorated innervation of the muscles that resulted in improved motor
      performances and hind-limb muscular tone. Finally, D-JNKI1 treatment slightly,
      but significantly increased lifespan in SMA mice. Thus, our results identify JNK
      as a promising target to reduce MN cell death and progressive skeletal muscle
      atrophy, providing insight into the role of JNK-pathway for developing
      alternative pharmacological strategies for the treatment of SMA.

PMID- 30233328
TI  - Chemogenetic Recruitment of Specific Interneurons Suppresses Seizure Activity.
AB  - Current anti-epileptic medications that boost synaptic inhibition are effective
      in reducing several types of epileptic seizure activity. Nevertheless, these
      drugs can generate significant side-effects and even paradoxical responses due to
      the broad nature of their action. Recently developed chemogenetic techniques
      provide the opportunity to pharmacologically recruit endogenous inhibitory
      mechanisms in a selective and circuit-specific manner. Here, we use chemogenetics
      to assess the potential of suppressing epileptiform activity by enhancing the
      synaptic output from three major interneuron populations in the rodent
      hippocampus: parvalbumin (PV), somatostatin (SST), and vasoactive intestinal
      peptide (VIP) expressing interneurons. To target different neuronal populations,
      promoter-specific cre-recombinase mice were combined with viral-mediated delivery
      of chemogenetic constructs. Targeted electrophysiological recordings were then
      conducted in an in vitro model of chronic, drug-resistant epilepsy. In addition,
      behavioral video-scoring was performed in an in vivo model of acutely triggered
      seizure activity. Pre-synaptic and post-synaptic whole cell recordings in brain
      slices revealed that each of the three interneuron types increase their firing
      rate and synaptic output following chemogenetic activation. However, the
      interneuron populations exhibited different effects on epileptiform discharges.
      Recruiting VIP interneurons did not change the total duration of epileptiform
      discharges. In contrast, recruiting SST or PV interneurons produced robust
      suppression of epileptiform synchronization. PV interneurons exhibited the
      strongest effect per cell, eliciting at least a fivefold greater reduction in
      epileptiform activity than the other cell types. Consistent with this, we found
      that in vivo chemogenetic recruitment of PV interneurons suppressed convulsive
      behaviors by more than 80%. Our findings support the idea that selective
      chemogenetic enhancement of inhibitory synaptic pathways offers potential as an
      anti-seizure strategy.

PMID- 30233320
TI  - Impairments in Oxidative Glucose Metabolism in Epilepsy and Metabolic Treatments
      Thereof.
AB  - There is mounting evidence that oxidative glucose metabolism is impaired in
      epilepsy and recent work has further characterized the metabolic mechanisms
      involved. In healthy people eating a traditional diet, including carbohydrates,
      fats and protein, the major energy substrate in brain is glucose. Cytosolic
      glucose metabolism generates small amounts of energy, but oxidative glucose
      metabolism in the mitochondria generates most ATP, in addition to biosynthetic
      precursors in cells. Energy is crucial for the brain to signal "normally," while
      loss of energy can contribute to seizure generation by destabilizing membrane
      potentials and signaling in the chronic epileptic brain. Here we summarize the
      known biochemical mechanisms that contribute to the disturbance in oxidative
      glucose metabolism in epilepsy, including decreases in glucose transport, reduced
      activity of particular steps in the oxidative metabolism of glucose such as
      pyruvate dehydrogenase activity, and increased anaplerotic need. This knowledge
      justifies the use of alternative brain fuels as sources of energy, such as
      ketones, TCA cycle intermediates and precursors as well as even medium chain
      fatty acids and triheptanoin.

PMID- 30233319
TI  - Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases.
AB  - Central nervous system (CNS) is one of the largest killers of people's health all
      over the world. The overactivation of the immune and inflammatory responses is
      considered as an important factor, contributing to the pathogenesis and
      progression of CNS disorders. Among all kinds of immune and inflammatory
      reaction, the inflammasome, a complex of proteins, has been drawn increasingly
      attention to by researchers. The initiation and activation of the inflammasome is
      involved in the onset of various kinds of diseases. The NLRP3 inflammasome, the
      most studied member of the inflammasome, is closely associated with many kinds of
      CNS disorders. Here in this review, the roles of the NLRP3 inflammasome in the
      pathogenesis and progression of several well-known CNS diseases would be
      discussed, including cerebrovascular diseases, neurodegenerative diseases,
      multiple sclerosis, depression as well as other CNS disorders. In addition,
      several therapeutic strategies targeting on the NLRP3 inflammasome for the
      treatment of CNS disorders would be described in this review.

PMID- 30233326
TI  - Inhibition of HIF-1alpha Reduced Blood Brain Barrier Damage by Regulating MMP-2
      and VEGF During Acute Cerebral Ischemia.
AB  - Increase of blood brain barrier (BBB) permeability after acute ischemia stroke is
      a predictor to intracerebral hemorrhage transformation (HT) for tissue
      plasminogen activator (tPA) thrombolysis and post-endovascular treatment.
      Previous studies showed that 2-h ischemia induced damage of BBB integrity and
      matrix metalloproteinase-2 (MMP-2) made major contribution to this disruption. A
      recent study showed that blocking beta2-adrenergic receptor (beta2-AR) alleviated
      ischemia-induced BBB injury by reducing hypoxia-inducible factor-1 alpha (HIF
      1alpha) level. In this study, we sought to investigate the interaction of HIF
      1alpha with MMP-2 and vascular endothelial growth factor (VEGF) in BBB injury
      after acute ischemia stroke. Rat suture middle cerebral artery occlusion (MCAO)
      model was used to mimic ischemia condition. Our results showed that ischemia
      produced BBB damage and MMP-2/9 upregulation was colocalized with Rhodamine
      dextran leakage. Pretreatment with YC-1, a HIF-1alpha inhibitor, alleviated 2-h
      ischemia-induced BBB injury significantly accompanied by decrease of MMP-2
      upregulation. In addition, YC-1 also prevented VEGF-induced BBB damage. Of note,
      VEGF was shown to be colocalized with neurons but not astrocytes. Taken together,
      BBB damage was reduced by inhibition of interaction of HIF-1alpha with MMP-2 and
      VEGF during acute cerebral ischemia. These findings provide mechanisms underlying
      BBB damage after acute ischemia stroke and may help reduce thrombolysis- and post
      endovascular treatment-related cerebral hemorrhage.

PMID- 30233321
TI  - AgRP/NPY Neuron Excitability Is Modulated by Metabotropic Glutamate Receptor 1
      During Fasting.
AB  - The potential to control feeding behavior via hypothalamic AgRP/NPY neurons has
      led to many approaches to modulate their excitability-particularly by
      glutamatergic input. In the present study using NPY-hrGFP reporter mice, we
      visualize AgRP/NPY neuronal metabotropic glutamate receptor 1 (mGluR1) expression
      and test the effect of fasting on mGluR1 function. Using the pharmacological
      agonist dihydroxyphenylglycine (DHPG), we demonstrate the enhanced capacity of
      mGluR1 to drive firing of AgRP/NPY neurons after overnight fasting, while
      antagonist 3-MATIDA reduces firing. Further, under synaptic blockade we
      demonstrate that DHPG acts directly on AgRP/NPY neurons to create a slow inward
      current. Using an in vitro approach, we show that emulation of intracellular
      signals associated with fasting by forskolin enhances DHPG induced
      phosphorylation of extracellularly regulated-signal kinase (1/2) in GT1-7 cell
      culture. We show in vivo that blocking mGluR1 by antagonist 3-MATIDA lowers
      fasting induced refeeding. In summary, this study identifies a novel layer of
      regulation on AgRP/NPY neurons integrated with whole body energy balance.

PMID- 30233324
TI  - Recent Findings on AMPA Receptor Recycling.
AB  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs) are
      tetrameric protein complexes that mediate most of the fast-excitatory
      transmission in response to the neurotransmitter glutamate in neurons. The
      abundance of AMPA-Rs at the surface of excitatory synapses establishes the
      strength of the response to glutamate. It is thus evident that neurons need to
      tightly regulate this feature, particularly in the context of all synaptic
      plasticity events, which are considered the biological correlates of higher
      cognitive functions such as learning and memory. AMPA-R levels at the synapse are
      regulated by insertion of newly synthesized receptors, lateral diffusion on the
      plasma membrane and endosomal cycling. The latter is likely the most important
      especially for synaptic plasticity. This process starts with the endocytosis of
      the receptor from the cell surface and is followed by either degradation, if the
      receptor is directed to the lysosomal compartment, or reinsertion at the cell
      surface through a specialized endosomal compartment called recycling endosomes.
      Although the basic steps of this process have been discovered, the details and
      participation of additional regulatory proteins are still being discovered. In
      this review article, we describe the most recent findings shedding light on this
      crucial mechanism of synaptic regulation.

PMID- 30233329
TI  - P/Q Type Calcium Channel Cav2.1 Defines a Unique Subset of Glomeruli in the Mouse
      Olfactory Bulb.
AB  - Voltage-gated calcium (Cav) channels are a prerequisite for signal transmission
      at the first olfactory sensory neuron (OSN) synapse within the glomeruli of the
      main olfactory bulb (MOB). We showed previously that the N-type Cav channel
      subunit Cav2.2 is present in the vast majority of glomeruli and plays a central
      role in presynaptic transmitter release. Here, we identify a distinct subset of
      glomeruli in the MOB of adult mice that is characterized by expression of the P/Q
      type channel subunit Cav2.1. Immunolocalization shows that Cav2.1+ glomeruli
      reside predominantly in the medial and dorsal MOB, and in the vicinity of the
      necklace glomerular region close to the accessory olfactory bulb. Few glomeruli
      are detected on the ventral and lateral MOB. Cav2.1 labeling in glomeruli
      colocalizes with the presynaptic marker vGlut2 in the axon terminals of OSNs.
      Electron microscopy shows that Cav2.1+ presynaptic boutons establish
      characteristic asymmetrical synapses with the dendrites of second-order neurons
      in the glomerular neuropil. Cav2.1+ glomeruli receive axonal input from OSNs that
      express molecules of canonical OSNs: olfactory marker protein, the ion channel
      Cnga2, and the phosphodiesterase Pde4a. In the main olfactory epithelium, Cav2.1
      labels a distinct subpopulation of OSNs whose distribution mirrors the topography
      of the MOB glomeruli, that shows the same molecular signature, and is already
      present at birth. Together, these experiments identify a unique Cav2.1+
      multiglomerular domain in the MOB that may form a previously unrecognized
      olfactory subsystem distinct from other groups of necklace glomeruli that rely on
      cGMP signaling mechanisms.

PMID- 30233323
TI  - Alterations of GABAergic Neuron-Associated Extracellular Matrix and Synaptic
      Responses in Gad1-Heterozygous Mice Subjected to Prenatal Stress.
AB  - Exposure to prenatal stress (PS) and mutations in Gad1, which encodes GABA
      synthesizing enzyme glutamate decarboxylase (GAD) 67, are the primary risk
      factors for psychiatric disorders associated with abnormalities in parvalbumin
      (PV)-positive GABAergic interneurons in the medial prefrontal cortex (mPFC).
      Decreased expression of extracellular matrix (ECM) glycoproteins has also been
      reported in patients with these disorders, raising the possibility that ECM
      abnormalities may play a role in their pathogenesis. To elucidate
      pathophysiological changes in ECM induced by the gene-environment interaction, we
      examined heterozygous GAD67-GFP (Knock-In KI; GAD67+/GFP) mice subjected to PS
      from embryonic day 15.0 to 17.5. Consistent with our previous study, we confirmed
      a decrease in the density of PV neurons in the mPFC of postnatal GAD67+/GFP mice
      with PS, which was concurrent with a decrease in density of PV neurons surrounded
      by perineuronal nets (PNNs), a specialized ECM important for the maturation,
      synaptic stabilization and plasticity of PV neurons. Glycosylation of alpha
      dystroglycan (alpha-DG) and its putative mediator fukutin (Fktn) in the ECM
      around inhibitory synapses has also been suggested to contribute to disease
      development. We found that both glycosylated alpha-DG and the mRNA level of Fktn
      were reduced in GAD67+/GFP mice with PS. None of these changes were detected in
      GAD67+/GFP naive mice or wild type (GAD67+/+) mice with PS, suggesting that both
      PS and reduced Gad1 gene expression are prerequisites for these changes. When
      assessing the function of interneurons in the mPFC of GAD67+/GFP mice with PS
      through evoked inhibitory post-synaptic currents (eIPSCs) in layer V pyramidal
      neurons, we found that the threshold stimulus intensity for eIPSC events was
      reduced and that the eIPSC amplitude was increased without changes in the paired
      pulse ratio (PPR). Moreover, the decay rate of eIPSCs was also slowed. In line
      with eIPSC, spontaneous IPSC (sIPSC) amplitude, frequency and decay tau were
      altered. Thus, our study suggests that alterations in the ECM mediated by gene
      environment interactions might be linked to the enhanced and prolonged GABA
      action that compensates for the decreased density of PV neurons. This might be
      one of the causes of the excitatory/inhibitory imbalance in the mPFC of
      psychiatric patients.

PMID- 30233331
TI  - Differential Roles of Mitochondrial Translocation of Active Caspase-3 and HMGB1
      in Neuronal Death Induced by Status Epilepticus.
AB  - Under pathophysiological conditions, aberrant mitochondrial dynamics lead to the
      different types of neuronal death: excessive mitochondrial fission provokes
      apoptosis and abnormal mitochondrial elongation induces necrosis. However, the
      underlying mechanisms how the different mitochondrial dynamics result in the
      distinct neuronal death patterns have been elusive. In the present study, status
      epilepticus (SE) evoked excessive mitochondrial fission in parvalbumin (PV) cells
      (one of GABAergic interneurons) and abnormal mitochondrial elongation in CA1
      neurons in the rat hippocampus. These impaired mitochondrial dynamics were
      accompanied by mitochondrial translocations of active caspase-3 and high mobility
      group box 1 (HMGB1) in PV cells and CA1 neurons, respectively. WY14643 (an
      activator of mitochondrial fission) aggravated SE-induced PV cell loss by
      enhancing active caspase-3 induction and its mitochondrial translocation, which
      were attenuated by Mdivi-1 (an inhibitor of mitochondrial fission). Mitochondrial
      HMGB1 import was not observed in PV cell. In contrast to PV cells, Mdivi-1
      deteriorated SE-induced CA1 neuronal death concomitant with mitochondrial HMGB1
      translocation, which was abrogated by WY14643. These findings suggest that SE
      induced aberrant mitochondrial dynamics may be involved in translocation of
      active caspase-3 and HMGB1 into mitochondria, which regulate neuronal apoptosis
      and necrosis, respectively.

PMID- 30233317
TI  - Studying Huntington's Disease in Yeast: From Mechanisms to Pharmacological
      Approaches.
AB  - Huntington's disease (HD) is a neurodegenerative disorder that leads to
      progressive neuronal loss, provoking impaired motor control, cognitive decline,
      and dementia. So far, HD remains incurable, and available drugs are effective
      only for symptomatic management. HD is caused by a mutant form of the huntingtin
      protein, which harbors an elongated polyglutamine domain and is highly prone to
      aggregation. However, many aspects underlying the cytotoxicity of mutant
      huntingtin (mHTT) remain elusive, hindering the efficient development of
      applicable interventions to counteract HD. An important strategy to obtain
      molecular insights into human disorders in general is the use of eukaryotic model
      organisms, which are easy to genetically manipulate and display a high degree of
      conservation regarding disease-relevant cellular processes. The budding yeast
      Saccharomyces cerevisiae has a long-standing and successful history in modeling a
      plethora of human maladies and has recently emerged as an effective tool to study
      neurodegenerative disorders, including HD. Here, we summarize some of the most
      important contributions of yeast to HD research, specifically concerning the
      elucidation of mechanistic features of mHTT cytotoxicity and the potential of
      yeast as a platform to screen for pharmacological agents against HD.

PMID- 30233332
TI  - Modeling Neural Adaptation in Auditory Cortex.
AB  - Neural responses recorded from auditory cortex exhibit adaptation, a stimulus
      specific decrease that occurs when the same sound is presented repeatedly.
      Stimulus-specific adaptation is thought to facilitate perception in noisy
      environments. Although adaptation is assumed to arise independently from cortex,
      this has been difficult to validate directly in vivo. In this study, we used a
      neural network model of auditory cortex with multicompartmental cell modeling to
      investigate cortical adaptation. We found that repetitive, non-adapted inputs to
      layer IV neurons in the model elicited frequency-specific decreases in simulated
      single neuron, population-level and local field potential (LFP) activity,
      consistent with stimulus-specific cortical adaptation. Simulated recordings of
      LFPs, generated solely by excitatory post-synaptic inputs and recorded from
      layers II/III in the model, showed similar waveform morphologies and stimulus
      probability effects as auditory evoked responses recorded from human cortex. We
      tested two proposed mechanisms of cortical adaptation, neural fatigue and neural
      sharpening, by varying the strength and type of inter- and intra-layer synaptic
      connections (excitatory, inhibitory). Model simulations showed that synaptic
      depression modeled in excitatory (AMPA) synapses was sufficient to elicit a
      reduction in neural firing rate, consistent with neural fatigue. However,
      introduction of lateral inhibition from local layer II/III interneurons resulted
      in a reduction in the number of responding neurons, but not their firing rates,
      consistent with neural sharpening. These modeling results demonstrate that
      adaptation can arise from multiple neural mechanisms in auditory cortex.

PMID- 30233330
TI  - Schwann Cell Responses and Plasticity in Different Dental Pulp Scenarios.
AB  - Mammalian teeth have evolved as dentin units that enclose a complex system of
      sensory innervation to protect and preserve their structure and function. In
      human dental pulp (DP), mechanosensory and nociceptive fibers form a dense
      meshwork of nerve endings at the coronal dentin-pulp interface, which arise from
      myelinated and non-myelinated axons of the Raschkow plexus (RP). Schwann cells
      (SCs) play a crucial role in the support, maintenance and regeneration after
      injury of these fibers. We have recently characterized two SC phenotypes
      hierarchically organized within the coronal and radicular DP in human teeth.
      Myelinating and non-myelinating SCs (nmSCs) display a high degree of plasticity
      associated with nociceptive C-fiber sprouting and axonal degeneration in response
      to DP injuries from dentin caries or physiological root resorption (PRR). By
      comparative immunolabeling, confocal and electron microscopy, we have
      characterized short-term adaptive responses of SC phenotypes to nerve injuries,
      and long-term changes related to aging. An increase of SCs characterizes the
      early responses to caries progression in association with axonal sprouting in
      affected DP domains. Moreover, during PRR, the formation of bands of Bungner is
      observed as part of SC repair tracks functions. On the other hand, myelinated
      axon density is significantly reduced with tooth age, as part of a gradual
      decrease in DP defense and repair capacities. The remarkable plasticity and
      capacity of SCs to preserve DP innervation in different dental scenarios
      constitutes a fundamental aspect to improve clinical treatments. This review
      article discusses the central role of myelinating and non-mSCs in long-term tooth
      preservation and homeostasis.

PMID- 30233334
TI  - Audio Feedback Associated With Body Movement Enhances Audio and Somatosensory
      Spatial Representation.
AB  - In the last years, the positive impact of sensorimotor rehabilitation training on
      spatial abilities has been taken into account, e.g., providing evidence that
      combined multimodal compared to unimodal feedback improves responsiveness to
      spatial stimuli. To date, it still remains unclear to which extent spatial
      learning is influenced by training conditions. Here we investigated the effects
      of active and passive audio-motor training on spatial perception in the auditory
      and proprioceptive domains on 36 healthy young adults. First, to investigate the
      role of voluntary movements on spatial perception, we compared the effects of
      active vs. passive multimodal training on auditory and proprioceptive spatial
      localization. Second, to investigate the effectiveness of unimodal training
      conditions on spatial perception, we compared the impact of only proprioceptive
      or only auditory sensory feedback on spatial localization. Finally, to understand
      whether the positive effects of multimodal and unimodal trainings generalize to
      the untrained part, both dominant and non-dominant arms were tested. Results
      indicate that passive multimodal training (guided movement) is more beneficial
      than active multimodal training (active exploration) and only in passive
      condition the improvement is generalized also on the untrained hand. Moreover, we
      found that combined audio-motor training provides the strongest benefit because
      it significantly affects both auditory and somatosensory localization, while the
      effect of a single feedback modality is limited to a single domain, indicating a
      cross-modal influence of the two domains. Therefore, the use of multimodal
      feedback is more efficient in improving spatial perception. These results
      indicate that combined sensorimotor signals are effective in recalibrating
      auditory and proprioceptive spatial perception and that the beneficial effect is
      mainly due to the combination of auditory and proprioceptive spatial cues.

PMID- 30233327
TI  - Glioma in Schizophrenia: Is the Risk Higher or Lower?
AB  - Whether persons with schizophrenia have a higher or lower incidence of cancer has
      been discussed for a long time. Due to the complex mechanisms and characteristics
      of different types of cancer, it is difficult to evaluate the exact relationship
      between cancers and schizophrenia without considering the type of tumor.
      Schizophrenia, a disabling mental illness that is now recognized as a
      neurodevelopmental disorder, is more correlated with brain tumors, such as
      glioma, than other types of tumors. Thus, we mainly focused on the relationship
      between schizophrenia and glioma morbidity. Glioma tumorigenesis and
      schizophrenia may share similar mechanisms; gene/pathway disruption would affect
      neurodevelopment and reduce the risk of glioma. The molecular defects of
      disrupted-in-schizophrenia-1 (DISC1), P53, brain-derived neurotrophic factor
      (BDNF) and C-X-C chemokine receptors type 4 (CXCR4) involved in schizophrenia
      pathogenesis might play opposite roles in glioma development. Many microRNAs
      (miRNAs) such as miR-183, miR-9, miR-137 and miR-126 expression change may be
      involved in the cross talk between glioma prevalence and schizophrenia. Finally,
      antipsychotic drugs may have antitumor effects. All these factors show that
      persons with schizophrenia have a decreased incidence of glioma; therefore,
      epidemiological investigation and studies comparing genetic and epigenetic
      aberrations involved in both of these complex diseases should be performed. These
      studies can provide more insightful knowledge about glioma and schizophrenia
      pathophysiology and help to determine the target/strategies for the prevention
      and treatment of the two diseases.

PMID- 30233335
TI  - Enriched Environment Exposure Enhances Social Interactions and Oxytocin
      Responsiveness in Male Long-Evans Rats.
AB  - Both social and physical stimuli contribute to the complexity of an animal's
      environment, influencing biobehavioral responses to subsequent challenges. In the
      current study, male Long-Evans rats were randomly assigned to an isolate (ISO),
      social control (SC) or social enriched (SE) group (n = 8 per group). The SC and
      SE conditions were group housed with the SE group exposed to physical enrichment
      stimuli that were natural as opposed to manufactured (e.g., hollowed out log
      instead of plastic hiding place). On three occasions during their 40-day enriched
      environment exposure, night/dark phase videos were obtained for 1 h during the
      early part of the dark phase. During this time, the SE animals exhibited
      significantly more social grooming with no differences between the SE and SC in
      the frequency of play or self-grooming bouts. Subsequently, all animals were
      assessed in social interaction and problem-solving escape tasks during the last
      week of the enriched environment exposure. SE rats exhibited increased digging
      bouts toward the restrained conspecific in the social interaction task whereas
      the other groups exhibited more escape responses. In the problem-solving task, SE
      animals exhibited a decreased latency to cross the barrier to escape from the
      predator odor (i.e., cat urine and fur). Neural analyses indicated increased
      oxytocin-immunoreactive (OT-ir) tissue in the SE supraoptic and paraventricular
      nuclei of the hypothalamus compared to the other groups. Interestingly, blood
      samples indicated lower peripheral corticosterone (CORT) and higher OT levels in
      the ISO animals when compared to the SC and SE animals, an effect retrospectively
      attributed to separation anxiety in the SE and SC animals in preparation for
      histology procedures. When the behavioral, neural and endocrine data were
      visualized as a multifaceted dataset via a multidimensional scaling analysis,
      however, an association between social enrichment and higher OT involvement was
      observed in the SE animals, as well as heightened stress responsivity in the ISO
      and SC groups. In sum, the SE animals exhibited a facilitation of social
      responses, problem-solving ability and OT immunoreactive responsiveness. These
      findings provide new information about the influences of both physical and social
      stimuli in dynamic and enriched environments.

PMID- 30233337
TI  - Long-Lasting Effects of Prenatal Ethanol Exposure on Fear Learning and
      Development of the Amygdala.
AB  - Prenatal ethanol exposure (PrEE) produces developmental abnormalities in brain
      and behavior that often persist into adulthood. We have previously reported
      abnormal cortical gene expression, disorganized neural circuitry along with
      deficits in sensorimotor function and anxiety in our CD-1 murine model of fetal
      alcohol spectrum disorders, or FASD (El Shawa et al., 2013; Abbott et al., 2016).
      We have proposed that these phenotypes may underlie learning, memory, and
      behavioral deficits in humans with FASD. Here, we evaluate the impact of PrEE on
      fear memory learning, recall and amygdala development at two adult timepoints.
      PrEE alters learning and memory of aversive stimuli; specifically, PrEE mice,
      fear conditioned at postnatal day (P) 50, showed deficits in fear acquisition and
      memory retrieval when tested at P52 and later at P70-P72. Interestingly, this
      deficit in fear acquisition observed during young adulthood was not present when
      PrEE mice were conditioned later, at P80. These mice displayed similar levels of
      fear expression as controls when tested on fear memory recall. To test whether
      PrEE alters development of brain circuitry associated with fear conditioning and
      fear memory recall, we histologically examined subdivisions of the amygdala in
      PrEE and control mice and found long-term effects of PrEE on fear memory
      circuitry. Thus, results from this study will provide insight on the
      neurobiological and behavioral effects of PrEE and provide new information on
      developmental trajectories of brain dysfunction in people prenatally exposed to
      ethanol.

PMID- 30233338
TI  - A Hypothesis of the Interaction of the Nitrergic and Serotonergic Systems in
      Aggressive Behavior Induced by Exposure to Lead.
AB  - The effects caused by exposure to lead (Pb) are still considered as a relevant
      health risk despite public policies aimed to restricting the use of this element.
      The toxicity limit in the blood (10 MUg/dL, established by the Center for Disease
      Control and Prevention) has been insufficient to prevent adverse effects and even
      lower values have been related to neurobehavioral dysfunctions in children.
      Currently, there is not a safe limit of exposure to Pb. A large body of evidence
      points to environmental pollutant exposure as the cause of predisposition to
      violent behavior, among others. Considering the evidence by our group and others,
      we propose that Pb exposure induces alterations in the brain vasculature,
      specifically in nitric oxide synthases (NOS), affecting in turn the serotonergic
      system and leading to heightened aggressive behavior in the exposed individuals.
      This review article describes the consequences of Pb exposure on the nitrergic
      and serotonergic systems as well as its relationship with aggressive behavior. In
      addition, it summarizes the available therapy to prevent damage in gestation and
      among infants.

PMID- 30233333
TI  - Glomerular Organization in the Antennal Lobe of the Oriental Fruit Fly Bactrocera
      dorsalis.
AB  - The oriental fruit fly, Bactrocera dorsalis is one of the most destructive pests
      of horticultural crops in tropical and subtropical Asia. The insect relies
      heavily on its olfactory system to select suitable hosts for development and
      reproduction. To understand the neural basis of its odor-driven behaviors, it is
      fundamental to characterize the anatomy of its olfactory system. In this study,
      we investigated the anatomical organization of the antennal lobe (AL), the
      primary olfactory center, in B. dorsalis, and constructed a 3D glomerular atlas
      of the AL based on synaptic antibody staining combined with computerized 3D
      reconstruction. To facilitate identification of individual glomeruli, we also
      applied mass staining of olfactory sensory neurons (OSNs) and projection neurons
      (PNs). In total, 64 or 65 glomeruli are identifiable in both sexes based on their
      shape, size, and relative spatial relationship. The overall glomerular volume of
      two sexes is not statistically different. However, eight glomeruli are sexually
      dimorphic: four (named AM2, C1, L2, and L3) are larger in males, and four are
      larger in females (A3, AD1, DM3, and M1). The results from anterograde staining,
      obtained by applying dye in the antennal lobe, show that three typical medial,
      media lateral, and lateral antennal-lobe tracts form parallel connections between
      the antennal lobe and protocerebrum. In addition to these three tracts, we also
      found a transverse antennal-lobe tract. Based on the retrograde staining of the
      calyx in the mushroom body, we also characterize the arrangement of roots and
      cell body clusters linked to the medial antennal-lobe tracts. These data provide
      a foundation for future studies on the olfactory processing of host odors in B.
      dorsalis.

PMID- 30233342
TI  - Corrigendum: Static and Dynamic Measures of Human Brain Connectivity Predict
      Complementary Aspects of Human Cognitive Performance.
AB  - [This corrects the article DOI: 10.3389/fnhum.2017.00420.].

PMID- 30233336
TI  - Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal
      Cord of Two Mouse Models of Restless Legs Syndrome.
AB  - Restless Legs Syndrome (RLS) is often and successfully treated with dopamine
      receptor agonists that target the inhibitory D3 receptor subtype, however there
      is no clinical evidence of a D3 receptor dysfunction in RLS patients. In
      contrast, genome-wide association studies in RLS patients have established that a
      mutation of the MEIS1 gene is associated with an increased risk in developing
      RLS, but the effect of MEIS1 dysfunction on sensorimotor function remain unknown.
      Mouse models for a dysfunctional D3 receptor (D3KO) and Meis1 (Meis1KO) were
      developed independently, and each animal expresses some features associated with
      RLS in the clinic, but they have not been compared in their responsiveness to
      treatment options used in the clinic. We here confirm that D3KO and Meis1KO
      animals show increased locomotor activities, but that only D3KO show an increased
      sensory excitability to thermal stimuli. Next we compared the effects of
      dopaminergics and opioids in both animal models, and we assessed D1 and D3
      dopamine receptor expression in the spinal cord, the gateway for sensorimotor
      processing. We found that Meis1KO share most of the tested behavioral properties
      with their wild type (WT) controls, including the modulation of the thermal pain
      withdrawal reflex by morphine, L-DOPA and D3 receptor (D3R) agonists and
      antagonists. However, Meis1KO and D3KO were behaviorally more similar to each
      other than to WT when tested with D1 receptor (D1R) agonists and antagonists.
      Subsequent Western blot analyses of D1R and D3R protein expression in the spinal
      cord revealed a significant increase in D1R but not D3R expression in Meis1KO and
      D3KO over WT controls. As the D3R is mostly present in the dorsal spinal cord
      where it has been shown to modulate sensory pathways, while activation of the
      D1Rs can activate motoneurons in the ventral spinal cord, we speculate that D3KO
      and Meis1KO represent two complementary animal models for RLS, in which the
      mechanisms of sensory (D3R-mediated) and motor (D1R-mediated) dysfunctions can be
      differentially explored.

PMID- 30233340
TI  - Neglect-Like Effects on Drawing Symmetry Induced by Adaptation to a Laterally
      Asymmetric Visuomotor Delay.
AB  - In daily interactions, our sensorimotor system accounts for spatial and temporal
      discrepancies between the senses. Functional lateralization between hemispheres
      causes differences in attention and in the control of action across the left and
      right workspaces. In addition, differences in transmission delays between
      modalities affect movement control and internal representations. Studies on motor
      impairments such as hemispatial neglect syndrome suggested a link between lateral
      spatial biases and temporal processing. To understand this link, we
      computationally modeled and experimentally validated the effect of laterally
      asymmetric delay in visual feedback on motor learning and its transfer to the
      control of drawing movements without visual feedback. In the behavioral
      experiments, we asked healthy participants to perform lateral reaching movements
      while adapting to delayed visual feedback in either left, right, or both
      workspaces. We found that the adaptation transferred to blind drawing and caused
      movement elongation, which is consistent with a state representation of the
      delay. However, the pattern of the spatial effect varied between conditions:
      whereas adaptation to delay in only the left workspace or in the whole workspace
      caused selective leftward elongation, adaptation to delay in only the right
      workspace caused drawing elongation in both directions. We simulated arm
      movements according to different models of perceptual and motor spatial asymmetry
      in the representation of delay and found that the best model that accounts for
      our results combines both perceptual and motor asymmetry between the hemispheres.
      These results provide direct evidence for an asymmetrical processing of delayed
      visual feedback that is associated with both perceptual and motor biases that are
      similar to those observed in hemispatial neglect syndrome.

PMID- 30233341
TI  - Empirical Comparison of Distributed Source Localization Methods for Single-Trial
      Detection of Movement Preparation.
AB  - The development of technologies for the treatment of movement disorders, like
      stroke, is still of particular interest in brain-computer interface (BCI)
      research. In this context, source localization methods (SLMs), that reconstruct
      the cerebral origin of brain activity measured outside the head, e.g., via
      electroencephalography (EEG), can add a valuable insight into the current state
      and progress of the treatment. However, in BCIs SLMs were often solely considered
      as advanced signal processing methods that are compared against other methods
      based on the classification performance alone. Though, this approach does not
      guarantee physiological meaningful results. We present an empirical comparison of
      three established distributed SLMs with the aim to use one for single-trial
      movement prediction. The SLMs wMNE, sLORETA, and dSPM were applied on data
      acquired from eight subjects performing voluntary arm movements. Besides the
      classification performance as quality measure, a distance metric was used to
      asses the physiological plausibility of the methods. For the distance metric,
      which is usually measured to the source position of maximum activity, we further
      propose a variant based on clusters that is better suited for the single-trial
      case in which several sources are likely and the actual maximum is unknown. The
      two metrics showed different results. The classification performance revealed no
      significant differences across subjects, indicating that all three methods are
      equally well-suited for single-trial movement prediction. On the other hand, we
      obtained significant differences in the distance measure, favoring wMNE even
      after correcting the distance with the number of reconstructed clusters. Further,
      distance results were inconsistent with the traditional method using the maximum,
      indicating that for wMNE the point of maximum source activity often did not
      coincide with the nearest activation cluster. In summary, the presented
      comparison might help users to select an appropriate SLM and to understand the
      implications of the selection. The proposed methodology pays attention to the
      particular properties of distributed SLMs and can serve as a framework for
      further comparisons.

PMID- 30233339
TI  - The Effects of Arousal and Approach Motivated Positive Affect on Cognitive
      Control. An ERP Study.
AB  - A growing body of research has demonstrated that affect modulates cognitive
      control modes such as proactive and reactive control. Several studies have
      suggested that positive affect decreases proactive control compared to neutral
      affect. However, these studies only focused on the valence of affect and often
      omitted two of its components: arousal and approach motivation. Therefore, we
      designed the present study to test the hypothesis that cognitive control modes
      would differ as a function of arousal and approach motivated positive affect. In
      our study, we used an AX-continuous performance task (AX-CPT), commonly used to
      examine shifts in proactive and reactive control. We also measured P3b,
      contingent negative variation (CNV), N2 and P3a components of event-related brain
      potentials (ERPs) as indicators of the use of cognitive control modes. The
      findings of the present study demonstrated that approach motivated positive
      affect modified only the P3b and the CNV without effects on the N2 and P3a
      components. However, arousal induced by pictures modified P3b, CNV and N2
      amplitudes. Specifically, the P3b amplitude was larger, and CNV amplitude was
      less negative in the high than in the low-approach motivated affect. In contrast,
      the P3b amplitude was larger and both the CNV and N2 amplitudes more negative in
      low- compared with high-arousal conditions. These ERP results suggest that
      approach motivated positive affect enhanced proactive control with no effect on
      reactive control. However, arousal influenced both proactive and reactive
      control. High arousal decreased proactive control and increased reactive control
      compared to low arousal. The present study provides novel insights into the
      relationship between affect, specifically, arousal and approach motivated
      positive affect and cognitive control modes. In addition, our results help to
      explain discrepancies found in previous research.

PMID- 30233343
TI  - Impulsiveness in Reactive Dieters: Evidence From Delay Discounting in Orthodontic
      Patients.
AB  - Introduction: Researchers have made efforts to distinguish the behavioral
      differences and underlying mechanisms that explain the various possible outcomes
      of dieting (success, failure and relapse). Although extensive research has
      demonstrated that eating behavior and individual impulsiveness are closely
      related to subjective appetite and decision making, very few studies have
      investigated how subjective and appetite impulsiveness is affected by reactive
      dieting. Methods: In the present study, we utilized the power of food scale (PFS)
      and the intertemporal choice task and to examine subjective appetite and
      impulsivity of decision making in orthodontic patients. As a result of their
      orthodontic devices and the subsequent pain and discomfort caused by eating,
      these patients become reactive dieters. In order to explore the dynamic influence
      of orthodontic treatment on appetite and impulsiveness, we collected data for
      both patients and control participants across three testing sections. We also
      computed a regression model for further exploration in explaining how potential
      factors contributed to different choices. Results: We found that the orthodontic
      group scored significantly lower in PFS than the control group, which indicated a
      suppression in appetite. Besides, reward and waiting time were significant
      factors in computational perspective. Moreover, although patients showed a bias
      in choosing smaller, immediate reward options, they exhibited a decrease in the
      delay discounting rate as treatment progressed. These findings confirm that
      subjective appetite and impulsiveness were inhibited due to reactive dieting.

PMID- 30233346
TI  - Bilateral Transcranial Magnetic Stimulation on DLPFC Changes Resting State
      Networks and Cognitive Function in Patients With Bipolar Depression.
AB  - Introduction: Bipolar patients have abnormalities in cognitive functions and
      emotional processing. Two resting state networks (RSNs), the default mode network
      (DMN) and the sensorimotor network (SMN), play a decisive role in these two
      functions. Dorsolateral prefrontal cortex (DLPFC) is one of the main areas in the
      central executive network (CEN), which is linked to the activities of each of the
      two networks. Studies have found DLPFC abnormalities in both hemispheres of
      patients with bipolar depression. We hypothesized that the bilateral repetitive
      transcranial magnetic stimulation (rTMS) of DLPFC would produce changes in the
      activity of both the SMN and DMN as well as relevant cognitive function in
      patients with bipolar depression that responded to treatment. Methods: 20
      patients with bipolar depression underwent 10 sessions of 1 Hz rTMS on right
      DLPFC with subsequent 10 Hz rTMS on left DLPFC. Changes in electroencephalography
      resting networks between pre and post rTMS were evaluated utilizing low
      resolution electromagnetic tomography (eLORETA). Depression symptom was assessed
      using the Beck Depression Inventory (BDI-II) and cognitive function was assessed
      by Verbal Fluency Test (VFT), Rey Auditory Verbal Learning Test (RAVLT), Stroop
      Test, and Wisconsin Card Sorting Test (WCST). Results: Responders to rTMS showed
      significantly lower DMN activity at baseline and a significant decrease in SMN
      connectivity after treatment. Non-responders did not significantly differ from
      the control group at the baseline and they showed higher activity in the SMN,
      visual network, and visual perception network compared to control group following
      treatment. Bilateral rTMS resulted in significant changes in the executive
      functions, verbal memory, and depression symptoms. No significant changes were
      observed in selective attention and verbal fluency. Conclusion: Bilateral
      stimulation of DLPFC, as the main node of CEN, results in changes in the activity
      of the SMN and consequently improves verbal memory and executive functions in
      patients with bipolar depression.

PMID- 30233344
TI  - Neuroimaging Metrics of Drug and Food Processing in Cocaine-Dependence, as a
      Function of Psychopathic Traits and Substance Use Severity.
AB  - Previous studies suggest that psychopathic traits commonly present as comorbid
      with substance use disorders. Moreover, neuroimaging and psychometric findings
      suggest that psychopathic traits may predispose individuals to a sensitized
      reward response to drugs. Given that substance use disorders are characterized by
      a neurocognitive bias toward drug-reward relative to non-drug reward, it is
      possible that heightened psychopathic characteristics may further predispose to
      this processing bias. To evaluate this possibility, we assessed psychopathic
      traits (measured using the PCL-R; Hare, 2003) in 105 probationers/parolees and
      evaluated the relationship between PCL-R scores, lifetime duration of drug use,
      and biases in neural response to drug- compared to food-related videos.
      Psychopathic traits (potentially driven by interpersonal/affective traits) were
      positively correlated with drug > food reactivity within the right insula and
      left amygdala. In addition, psychopathic traits modulated the relationship
      between drug use and drug > food reactivity within the left dorsomedial
      prefrontal cortex, right insula, and left caudate nucleus. Specifically, lifetime
      duration of drug use correlated positively with drug > food reactivity in
      participants with lower levels of psychopathic traits and correlated negatively
      with drug > food reactivity in individuals with higher levels of psychopathic
      traits. These results help reconcile prior studies on psychopathy and drug
      stimulus processing and provide neurocognitive support for the notion that
      psychopathic traits serve as an underlying risk factor for substance use
      disorders. These results suggest that different treatment regimens for substance
      abuse for individuals with higher or lower levels of psychopathy may be
      beneficial and suggest that reduction of neurocognitive biases to drug-related
      stimuli may offer useful targets for future treatment protocols.

PMID- 30233345
TI  - Brain Signatures of New (Pseudo-) Words: Visual Repetition in Associative and Non
      associative Contexts.
AB  - The contribution of two different training contexts to online, gradual lexical
      acquisition was investigated by event-related potentials (ERPs) elicited by new,
      word-like stimuli. Pseudowords were repeatedly preceded by a picture representing
      a well-known object (semantic-associative training context) or by a hash mark
      (non-associative training context). The two training styles revealed differential
      effects of repetition in both behavioral and ERPs data. Repetition of pseudowords
      not associated with any stimulus gradually enhanced the late positive component
      (LPC) as well as speeded lexical categorization of these stimuli, suggesting the
      formation of episodic memory traces. However, repetition under the semantic
      associative context caused higher reduction in N400 component and categorization
      latencies. This result suggests the facilitation in the lexico-semantic
      processing of pseudowords as a consequence of their progressive associations to
      picture-concepts, going beyond the visual memory trace that is generated under
      the non-associative context.

PMID- 30233349
TI  - Information Theory, Developmental Psychology, and the Baldwin Effect.
AB  - As part of the extended evolutionary synthesis, there has recently been a new
      emphasis on the effects of biological development on genetic inheritance and
      variation. The exciting new directions taken by those in the community have by a
      pre-history filled with related ideas that were never given a rigorous foundation
      or combined coherently. Part of the historical background of the extended
      synthesis is the work of James Mark Baldwin on his so-called "Baldwin Effect."
      Many variant re-interpretations of his work obscure the original meaning of the
      Baldwin Effect. This paper emphasizes a new approach to the Baldwin Effect,
      focusing on his work in developmental psychology and how that would impact
      evolution. We propose a novel population genetics model of the Baldwin Effect.
      First, the impact of a kind of learning process motivated by motor babbling, in
      the developmental psychology literature, on evolution; second, that Information
      theoretic phenotype reshaping speeds up evolution compared to populations without
      this kind of learning. The basic idea behind the model is to allow the organism
      to apply abstraction to his initial phenotype to situate it within one of a few
      different classes of phenotypes in the local neighborhood of a fitness maximum.
      The reshaping of the phenotype space thereby allows the organism to reach a
      nearby fitness maximum. By so doing, valleys in the fitness landscape are leveled
      out, making a rugged fitness landscape into a set of mesas and plateaus with
      increasing height. Using this model we can show the first sizeable speed-up for
      the Baldwin Effect compared to ordinary population genetics. We also introduce an
      information-theoretic foundation for the Baldwin Effect, which may be of
      independent interest.

PMID- 30233348
TI  - BRANT: A Versatile and Extendable Resting-State fMRI Toolkit.
AB  - Data processing toolboxes for resting-state functional MRI (rs-fMRI) have
      provided us with a variety of functions and user friendly graphic user interfaces
      (GUIs). However, many toolboxes only cover a certain range of functions, and use
      exclusively designed GUIs. To facilitate data processing and alleviate the burden
      of manually drawing GUIs, we have developed a versatile and extendable MATLAB
      based toolbox, BRANT (BRAinNetome fmri Toolkit), with a wide range of rs-fMRI
      data processing functions and code-generated GUIs. During the implementation, we
      have also empowered the toolbox with parallel computing techniques, efficient
      file handling methods for compressed file format, and one-line scripting. In
      BRANT, users can find rs-fMRI batch processing functions for preprocessing, brain
      spontaneous activity analysis, functional connectivity analysis, complex network
      analysis, statistical analysis, and results visualization, while developers can
      quickly publish scripts with code-generated GUIs.

PMID- 30233347
TI  - The Experience of Pleasure: A Perspective Between Neuroscience and
      Psychoanalysis.
AB  - Pleasure is more than a mere sensory event, but rather it can be conceptualized
      as a complex, multiform experience involving memory, motivation, homeostasis,
      and, sometimes, negative affects. According to Freud, affect is a perceptual
      modality that registers the internal drive state of the subject rather than the
      objective experience of the external world, and the quality of this perceptual
      modality is calibrated in degrees of pleasure and displeasure. Within this
      conceptual framework, the aim of drive is always pleasure, and objects become
      significant in so far as they provide a way of discharging drives pressure.
      Subsequent conceptual psychoanalytic developments have partially rejected such
      metapsychological theorizations, postulating that other intrinsic motivations
      that are independent from libido can be observed in humans. Intrinsic motivation
      broadly refers to a set of psychological concepts including the inherent
      propensity to pursue one's choices, to seek out novelty and challenges, to
      satisfy curiosity and competence, and to extend one's capacities and control over
      events. What these concepts have in common is an inner endorsement of one's
      action, which is the sense that action is self-generated and is one's own. The
      notions of pleasure, drives, and affects are all of utmost importance for a
      neuropsychoanalytic understanding of mental functioning, due to their capability
      to explain desire, thought, and behavior from the perspective of human subjective
      experience. The purpose of this paper is thus to discuss psychoanalytic
      conceptual developments that have addressed pleasure, drives, and affects, in the
      light of recent findings coming from neurosciences. In particular, we will
      explore for insights from Panksepp's theory of primary-process emotional
      feelings, including the notion of "wanting" and "liking" as dissociable
      components of reward. In the last part of the paper, we will indicate possible
      theoretical implications for a neuropsychoanalytic understanding of libido
      independent intrinsic motivations and their relationship with the self, including
      neuroscientific observations on self-related processes, agency, body-ownerships,
      and attachment.

PMID- 30233350
TI  - Shaping of Shared Autonomous Solutions With Minimal Interaction.
AB  - A fundamental problem in creating successful shared autonomy systems is enabling
      efficient specification of the problem for which an autonomous system can
      generate a solution. We present a general paradigm, Interactive Shared Solution
      Shaping (IS3), broadly applied to shared autonomous systems where a human can use
      their domain knowledge to interactively provide feedback during the autonomous
      planning process. We hypothesize that this interaction process can be optimized
      so that with minimal interaction, near-optimal solutions can be achieved. We
      examine this hypothesis in the space of resource-constrained mobile search and
      surveillance and show that without directly instructing a robot or complete
      communication of a believed target distribution, the human teammate is able to
      successfully shape the generation of an autonomous search route. This ability is
      demonstrated in three experiments that show (1) the IS3 approach can improve
      performance in that routes generated from interactions in general reduce the
      variance of the target detection performance, and increase overall target
      detection; (2) the entire IS3 autonomous route generation system's performance,
      including cost of interaction along with movement cost, experiences a tradeoff
      between performance vs. numbers of interactions that can be optimized; (3) the
      IS3 autonomous route generation system is able to perform within constraints by
      generating tours that stay under budget when executed by a real robot in a
      realistic field environment.

PMID- 30233352
TI  - Cholinergic Pathway SNPs and Postural Control in 477 Older Adults.
AB  - Objective: To determine whether single nucleotide polymorphisms (SNPs) of the
      cholinergic system and quantitative parameters of postural control are associated
      in healthy older adults. This is a cross-sectional analysis from the TREND study.
      Methods: All participants performed a static postural control task for 30 s on a
      foam pad in semitandem stance and eyes closed. We analyzed mean power frequency
      (MPF), area, acceleration, jerk, and velocity from a mobile sensor worn at the
      lower back using a validated algorithm. Genotypes of four SNPs in genes involved
      in the cholinergic system (SLC5A7, CHAT, BCHE, CHRNA4) were extracted from the
      NeuroX chip. All participants present a normal neurological examination and a
      Minimental state examination score >24. Results: Four hundred and seventy seven
      participants were included. Mean age was 69 years, 41% were female. One SNP of
      the cholinergic pathway was significantly associated with a quantitative postural
      control parameter. The minor allele of rs6542746 in SLC5A7 was associated with
      lower MPF (4.04 vs. 4.22 Hz; p = 3.91 * 10-4). Moreover, the following
      associations showed trends toward significance: minor allele of rs6542746 in
      SLC5A7 with higher anteroposterior acceleration (318 vs. 287 mG; p = 0.005), and
      minor allele of rs3810950 in CHAT with higher mediolateral acceleration [1.77 vs.
      1.65 log(mG); p = 0.03] and velocity [1.83 vs. 1.74 log(mm/s); p = 0.019].
      Intraindividual occurrence of rs6542746 and rs3810950 minor alleles was dose
      dependently related with lower MPF (p = 0.004). Conclusion: This observational
      study suggests an influence of SNPs of the cholinergic pathway on postural
      control in older adults.

PMID- 30233354
TI  - Clinical Data Analytics With Time-Related Graphical User Interfaces: Application
      to Pharmacovigilance.
AB  - Pharmacovigilance consists in monitoring and preventing the occurrence of adverse
      drug reactions. This activity can be time-consuming because it requires the
      collection of both patient and medication information. In this paper, we present
      two visualization and data mining applications to make this task easier for the
      practitioner. These tools have been developed and tested using the biomedical
      data warehouse eHOP (Hospital Biomedical Data Warehouse) of the Rennes University
      Hospital Centre. The first application is a tool to visualize the patient
      electronic health record in the form of a timeline. All patient data is collected
      and displayed chronologically. The usability test of the timeline has been very
      positive (SUS score: 82.5) and the tool is now available for practitioners in
      their daily practice. The second application is a tool to visualize and search
      the sequences of a patient cohort. The visual interface allow user to quickly
      visualize sequences. A query builder allows user to search for sequences in
      relation with a reference sequence, such as a prescription sequence followed by
      an abnormal biological value. The sequences are then visually aligned with this
      reference sequence and ranked by similarity. The GSP (Generalized Sequential
      Pattern) and Apriori algorithms allow us to display a summary of the sequences
      list by searching for common sequences and associations. The tool was tested on a
      use case which consisted in detection of inappropriate drug administration.
      Compared to a random order, we showed this ranking system saved the practitioner
      time in this task (to analyze one sequence, 3.49 +/- 3.54 vs. 2.26 +/- 2.86 s, p
      = 0.0003). These two visualization and data mining applications will help the
      daily practice of pharmacovigilance.

PMID- 30233353
TI  - Factors Explaining Language Performance After Training in Elders With and Without
      Subjective Cognitive Decline.
AB  - The present study explores if cognitive reserve, executive functions, and working
      memory capacity are predictive of performance in the language domain
      (specifically in sentence comprehension and naming) after a cognitive training
      intervention. Sixty-six Spanish older adults voluntarily participated in the
      study, classified either as older adults with subjective cognitive decline
      according to Jessen et al.'s (2014) criteria (n = 35; 70.94 +/- 4.16 years old)
      or cognitively intact (n = 31; 71.34 +/- 4.96 years old). Written sentence
      comprehension and visual confrontation naming were assessed both immediately
      after recruitment (at the baseline), and then 6 months later, once each
      participant had completed his/her cognitive training (a well-known program in
      Spain, called UMAM; English translation: Madrid City Council Memory Unit
      Program). Cognitive reserve, executive functions (cognitive flexibility and
      controlled interference efficiency), and working memory capacity were measured
      for all participants at the baseline. Results pointed out that the subjective
      cognitive decline group presented greater benefits in the language domain than
      cognitively intact participants. We also observed that lower executive
      functioning and working memory capacity at the baseline predicted larger benefits
      in language performance after training, but only in the group of cognitively
      intact older adults. However, selected predictors hardly explained subjective
      cognitive decline participants' results in language performance after training.

PMID- 30233351
TI  - Natural Molecules From Chinese Herbs Protecting Against Parkinson's Disease via
      Anti-oxidative Stress.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease
      after Alzheimer's disease, affecting about 7-10 million patients worldwide. The
      major pathological features of PD include loss of dopaminergic (DA) neurons in
      the substantia nigra pars compacta (SNpc) of the midbrain and the presence of
      alpha-synuclein-enriched Lewy bodies. Although the mechanism underlying PD
      pathogenesis remains to be elucidated, oxidative stress induced by the
      overproduction of reactive oxygen species (ROS) is widely accepted to be a key
      pathogenic factors. ROS cause oxidative damage to proteins, lipids, and DNA,
      which subsequently lead to neurodegeneration. Great efforts have been made to
      slow or stop the progress of PD. Unfortunately there is no effective cure for PD
      till now. Compounds with good antioxidant activity represent the promising
      candidates for therapeutics of PD. Some natural molecules from Chinese herbs are
      found to have good antioxidant activity. Both in vitro and in vivo studies
      demonstrate that these natural molecules could mitigate the oxidative stress and
      rescue the neuronal cell death in PD models. In present review, we summarized the
      reported natural molecules that displayed protective effects in PD. We also
      addressed the possible signal pathway through which natural molecules achieved
      their antioxidative effects and mitigate PD phenotypes. Hopefully it will pave
      the way to better recognize and utilize Chinese herbs for the treatment of PD.

PMID- 30233355
TI  - Efficacy and Safety of Oral TDF-Based Pre-exposure Prophylaxis for Men Who Have
      Sex With Men: A Systematic Review and Meta-Analysis.
AB  - Background: Pre-exposure prophylaxis (PrEP) is used as an HIV prevention method
      by people at substantial risk of HIV infection. This systematic review and meta
      analysis evaluates current clinical evidence for use of oral TDF-based PrEP among
      men who have sex with men. Methods: A comprehensive literature search in PubMed,
      web of science, Google Scholar and ClinicalTrials.gov was performed. A random
      effects meta-analysis was conducted using the event rate (ER) for estimation of
      the incidence of HIV and grade 3 or 4 adverse events (AE) among PrEP arm and
      using risk ratio (RR) for comparison of incidence of HIV and grade 3 or 4 AE
      between PrEP recipients and PrEP non-users. Blood-based adherence levels were
      also divided into three categories with reference to previous meta-analysis.
      Subgroup meta-analysis was also performed to evaluate whether blood-based
      adherence levels moderated the effect of TDF-based PrEP on HIV incidence.
      Narrative review was used due to inconsistent measurements of risk behavior and
      drug resistance. This review is registered on the PROSPERO database
      (CRD42017077965). Results: Fourteen studies were included in the review. Oral TDF
      based PrEP significantly reduced HIV incidence with minimum drug resistance and
      tolerable safety risks (HIV incidence, ER = 1.1%, 95% CI 0.6-2.0%, p < 0.001, RR
      = 0.244, 95% CI 0.111-0.537, p < 0.001 and grade 3 or 4 AEs, ER = 13.0%, 95% CI
      9.9-16.9%, p < 0.001, RR = 1.059, 95% CI 0.824-1.362, p = 0.653). Oral TDF-based
      PrEP was more effective in reducing HIV incidence with high levels of blood-based
      PrEP adherence (ER, 0.4%) compared to moderate adherence (2.9%; p < 0.001). Most
      studies found no association between PrEP use and self-reported sexual behavior.
      Conclusion: Oral TDF-based PrEP is an effective intervention to prevent against
      HIV infection among MSM. Well-designed implementation science studies that
      integrate sociobehavioral and biomedical interventions are needed to identify
      optimal PrEP delivery models in different populations to translate biomedical
      efficacy into real-world efficacy.

PMID- 30233356
TI  - The Shared Ethical Responsibility of Medically and Non-medically Qualified
      Experts in Human Drug Development Teams.
AB  - The complexity of developing and applying increasingly sophisticated new
      medicinal products has led to the participation of many non-medically qualified
      scientists in multi-disciplinary non-clinical and clinical drug development teams
      world-wide. In this introductory paper to the "IFAPP International Ethics
      Framework for Pharmaceutical Physicians and Medicines Development Scientists" it
      is argued that all members of such multidisciplinary teams must share the
      scientific and ethical responsibilities since they all influence directly or
      indirectly both the outcome of the various phases of the medicines development
      projects and the safety of the research subjects involved. The participating
      medical practitioner retains the overriding responsibility and the final decision
      to stop a trial if the well-being of the research subjects is seriously
      endangered. All the team members should follow the main ethical principles
      governing human research, the respect for autonomy, justice, beneficence and non
      maleficence. Nevertheless, the weighing of these principles might be different
      under various conditions according to the specialty of the members.

PMID- 30233357
TI  - Mouse Mast Cell Protease 4 Deletion Protects Heart Function and Survival After
      Permanent Myocardial Infarction.
AB  - Chymase, a mast cell serine protease involved in the generation of multiple
      cardiovascular factors, such as angiotensin II and endothelin-1 (ET-1), is
      elevated and participates in tissue degeneration after permanent myocardial
      infarction (PMI). Anesthetized 4-month old male wild-type (WT) C57BL/6J mice and
      mouse mast cell protease-4 knockout (mMCP-4 KO) congeners were subjected to
      ligation of the left anterior descending (LAD) coronary artery. A group of mice
      was then subjected to Kaplan-Meier 28-day survival analysis. In another group of
      mice, 18F-fluorodeoxyglucose positron emission tomography (PET) was performed to
      evaluate heart function and the infarcted zone 3 days post-PMI surgery. Cardiac
      morphology following PMI was evaluated on formalin-fixed heart slices and
      glycoproteomic analysis was performed using mass spectrometry. Finally, cardiac
      and lung tissue content of immunoreactive ET-1 was determined. PMI caused 60%
      mortality in WT mice, due to left ventricular wall rupture, and 7% in mMCP-4 KO
      mice. Cardiac PET analysis revealed a significant reduction in left ventricular
      volume (systolic and diastolic) and preserved the ejection fraction in mMCP-4 KO
      compared to WT animals. The infarcted area, apoptotic signaling and wall
      remodeling were significantly decreased in mMCP-4 KO mice compared to their WT
      congeners, while collagen deposition was increased. Glycoproteomic analysis
      showed an increase in apolipoprotein A1, an established chymase substrate in mMCP
      4 KO mice compared to WT mice post-PMI. ET-1 levels were increased in the lungs
      of WT, but not mMCP-4 KO mice, 24 h post-PMI. Thus, the genetic deletion of mMCP
      4 improved survival and heart function post-PMI.

PMID- 30233359
TI  - Potential Metabolic Drug-Drug Interaction of Citrus aurantium L. (Rutaceae)
      Evaluating by Its Effect on 3 CYP450.
AB  - Aim:Fructus aurantii (FA) is widely used in clinic as an expectorant and
      digestant herb in traditional Chinese medicine and proven to have a variety of
      pharmacological functions. FA is close to grapefruit either by botanical taxonomy
      or by their same components (flavonoids, etc.) and grapefruit has been proven to
      cause drug-drug interaction when co-administrated with CYP3A4 substrates.
      Besides, FA contains many compounds, such as flavonoids, which have been reported
      to impact the expressions of CYP450. However, the effect of FA on CYP450, whose
      change may affect drug safety and clinical efficacy attributed to drug-drug
      interaction, still remains unknown. Methods: The protein, mRNA expression and
      enzyme activity of CYP1A2, CYP3A4, and CYP2E1 in rat were determined by Western
      Blotting, RT-PCR method, the cocktail method, respectively, after orally
      administration of FA in succession for 7 days. CYP1A2, CYP3A4, and CYP2E1 mRNA
      expression were investigated in HepG2 cells following FA-medicated serum
      incubation for 24 h. Results: In rat, compared to the control group, CYP1A2,
      CYP3A4 protein, and mRNA expression were significantly induced consistent with
      the corresponding CYP activities; the protein expression of CYP2E1 was
      significantly upregulated, while the corresponding mRNA expression and enzyme
      activity showed no significant change. In HepG2 cells, compared to the control
      group, the mRNA expression of CYP1A2 and CYP3A4 was up-regulated statistically
      while CYP2E1 mRNA expression was not significantly induced or inhibited.
      Conclusion: FA may be a potential slight inducer of CYP1A2 and CYP3A4 and is
      unlikely to impact CYP2E1 until clinical researches are conducted.

PMID- 30233360
TI  - Activation of Nrf2/HO-1 Pathway by Nardochinoid C Inhibits Inflammation and
      Oxidative Stress in Lipopolysaccharide-Stimulated Macrophages.
AB  - The roots and rhizomes of Nardostachys chinensis have neuroprotection and
      cardiovascular protection effects. However, the specific mechanism of N.
      chinensis is not yet clear. Nardochinoid C (DC) is a new compound with new
      skeleton isolated from N. chinensis and this study for the first time explored
      the anti-inflammatory and anti-oxidant effect of DC. The results showed that DC
      significantly reduced the release of nitric oxide (NO) and prostaglandin E2
      (PGE2) in lipopolysaccharide (LPS)-activated RAW264.7 cells. The expression of
      pro-inflammatory proteins including inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) were also obviously inhibited by DC in LPS-activated
      RAW264.7 cells. Besides, the production of interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) were also remarkably inhibited by DC in LPS
      activated RAW264.7 cells. DC also suppressed inflammation indicators including
      COX-2, PGE2, TNF-alpha, and IL-6 in LPS-stimulated THP-1 macrophages.
      Furthermore, DC inhibited the macrophage M1 phenotype and the production of
      reactive oxygen species (ROS) in LPS-activated RAW264.7 cells. Mechanism studies
      showed that DC mainly activated nuclear factor erythroid 2-related factor 2
      (Nrf2) signaling pathway, increased the level of anti-oxidant protein heme
      oxygenase-1 (HO-1) and thus produced the anti-inflammatory and anti-oxidant
      effects, which were abolished by Nrf2 siRNA and HO-1 inhibitor. These findings
      suggested that DC could be a new Nrf2 activator for the treatment and prevention
      of diseases related to inflammation and oxidative stress.

PMID- 30233358
TI  - Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development
      of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise.
AB  - Asiatic acid (AA) is a naturally occurring aglycone of ursane type pentacyclic
      triterpenoids. It is abundantly present in many edible and medicinal plants
      including Centella asiatica that is a reputed herb in many traditional medicine
      formulations for wound healing and neuropsychiatric diseases. AA possesses
      numerous pharmacological activities such as antioxidant and anti-inflammatory and
      regulates apoptosis that attributes its therapeutic effects in numerous diseases.
      AA showed potent antihypertensive, nootropic, neuroprotective, cardioprotective,
      antimicrobial, and antitumor activities in preclinical studies. In various in
      vitro and in vivo studies, AA found to affect many enzymes, receptors, growth
      factors, transcription factors, apoptotic proteins, and cell signaling cascades.
      This review aims to represent the available reports on therapeutic potential and
      the underlying pharmacological and molecular mechanisms of AA. The review also
      also discusses the challenges and prospects on the pharmaceutical development of
      AA such as pharmacokinetics, physicochemical properties, analysis and structural
      modifications, and drug delivery. AA showed favorable pharmacokinetics and found
      bioavailable following oral or interaperitoneal administration. The studies
      demonstrate the polypharmacological properties, therapeutic potential and
      molecular mechanisms of AA in numerous diseases. Taken together the evidences
      from available studies, AA appears one of the important multitargeted
      polypharmacological agents of natural origin for further pharmaceutical
      development and clinical application. Provided the favorable pharmacokinetics,
      safety, and efficacy, AA can be a promising agent or adjuvant along with
      currently used modern medicines with a pharmacological basis of its use in
      therapeutics.

PMID- 30233363
TI  - Availability and Affordability of Drugs With a Conditional Approval by the
      European Medicines Agency; Comparison of Korea With Other Countries and the
      Implications.
AB  - Introduction: There have been concerns with the availability and affordability of
      EMA's recently approved medicines with a conditional approval in Korea. This
      needs to be addressed to provide future guidance to the authorities in Korea.
      Objective: Compare the availability and affordability of medicines with a
      conditional approval by the European Medicines Agency (EMA) among 12 countries
      (United States, United Kingdom, France, Germany, Switzerland, Italy, Japan,
      Canada, Taiwan, Australia, New Zealand, and Korea) in light of access to medicine
      concerns in Korea. Methods: Thirteen medicines were selected and compared in
      terms of their availability and affordability across 12 countries. Approval rate
      for the selected medicines and time lag to approval on the basis of EMA's
      approval dates were calculated. Reimbursement status and prices were compared as
      proxies of affordability. Results: The average approval rate was 31.9% for the
      selected medicines for all countries outside the EU countries. The highest rate
      was in United States (69.2%) followed by Korea and Switzerland (46.5%). An
      average of 238 days was taken among the countries for approval. The United States
      (median: -355 days) was the country where the medicines were most rapidly
      approved. Korea (152 days) ranked the fifth most rapidly approving country. An
      average listing or reimbursement rate for all countries was 54.1%. The United
      States ranked 100% for the listing of their approved medicines followed by
      Germany (92.3%). Korea (66.7%) ranked eighth. Price dispersion ranged from 1.1 to
      3.1. Korean prices of the selected medicines were found to be neither high nor
      low when compared to other countries. Conclusion: Korea was found to be a country
      where marketing authorization for more medicines tended to be made and subsequent
      reimbursement and pricing were not rigid even generous compared to other Asian
      pacific countries. Korean drug benefit policies for listing and pricing did not
      appear to hinder access to medicines even with a conditional approval in
      comparison with others.

PMID- 30233362
TI  - The Bone-Protecting Efficiency of Chinese Medicines Compared With Western
      Medicines in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of
      Comparative Studies.
AB  - Background: Rheumatoid Arthritis (RA) is a systemic autoimmune disease leading to
      joint destruction. The prevention of bone and cartilage destruction has received
      increased attention in recent years. Objective: To evaluate the current evidences
      regarding the bone-protecting efficacy of Chinese medicine or the combination of
      Chinese medicine and Western medicine for RA. Methods: We comprehensively
      searched PubMed, Embase, the Cochrane Library (www.thecochranelibrary.com), the
      China National Knowledge Infrastructure (CNKI), the Database for Chinese
      Technical Periodicals (VIP), and SinoMed. We then performed a systematic review
      and cumulative meta-analysis of all randomized controlled trials (RCTs) assessing
      the two therapy methods. Results: Sixteen studies including 1,171 patients were
      included in the final analysis. The results showed that Chinese medicine could
      significantly improve the bone mineral density (BMD) (mean difference [MD] = 0.05
      /g.cm-2, 95% CI [0.03, 0.08], P < 0.00001), and decrease the serum matrix
      metalloproteinase 3 (MMP-3) ([SMD] = -2.84, 95% CI [-4.22, -1.47], P < 0.0001).
      Conclusions: Chinese medicine may provide an efficiently alternative choice for
      the treatment of RA in terms of the bone-protecting efficiency. Given the
      inherent limitations of the included studies, future well-designed RCTs are
      required to confirm and update the findings of this analysis.

PMID- 30233364
TI  - Combined Use of Emodin and Ginsenoside Rb1 Exerts Synergistic Neuroprotection in
      Cerebral Ischemia/Reperfusion Rats.
AB  - Acute ischemic stroke (AIS) generally causes neurological dysfunction and poses a
      serious threat to public health. Here, we aimed to assess the independent and
      combined effects of ginsenoside Rb1 (GRb1) and Emodin on neuroprotection through
      regulating Connexin 43 (Cx43) and Aquaporin 4 (AQP4) expression in cerebral
      ischemia/reperfusion (I/R) model rats. Adult male Sprague-Dawley (SD) rats were
      randomly divided into five groups: sham group, I/R group, Emodin group, GRb1
      group and Emodin+GRb1 group. They were further allocated to four subgroups
      according to the 6h, 1d, 3d, and 7d time points except the sham group. Based on
      the modified Longa suture method, the focal cerebral I/R model was established by
      middle cerebral artery occlusion (MCAO). The neurological deficit scores (NDS),
      blood brain barrier (BBB) permeability and cerebral infarction area were assessed
      at each corresponding time point. Cx43 and AQP4 levels were assessed by Real-time
      PCR and Immunofluorescence. Compared with I/R group, both the independent and
      combined use of GRb1 and Emodin could alleviate NDS, reduce the BBB permeability,
      reduce the infarction area and down-regulate Cx43 and AQP4 expression at 6h, 1d,
      3d, and 7d after I/R (P < 0.05). The Emodin+GRb1 group had more significant
      effects than Emodin group and GRb1 group (P < 0.05). In conclusion, the
      combination of Emodin and GRb1 exerts synergistically neuroprotective functions
      through regulating AQP4 and Cx43 after I/R.

PMID- 30233365
TI  - Behavioral Effects of a Potential Novel TAAR1 Antagonist.
AB  - The trace amine associated receptor 1 (TAAR1) is a G-protein coupled receptor
      expressed in the monoaminergic regions of the brain, and represents a potential
      novel therapeutic target for the treatment of neurological disorders. While
      selective agonists for TAAR1 have been successfully identified, only one high
      affinity TAAR1 antagonist has been described thus far. We previously identified
      four potential low potency TAAR1 antagonists through an in silico screen on a
      TAAR1 homology model. One of the identified antagonists (compound 22) was
      predicted to have favorable physicochemical properties, which would allow the
      drug to cross the blood brain barrier. In vivo studies were therefore carried out
      and showed that compound 22 potentiates amphetamine- and cocaine-mediated
      locomotor activity. Furthermore, electrophysiology experiments demonstrated that
      compound 22 increased firing of dopamine neurons similar to EPPTB, the only known
      TAAR1 antagonist. In order to assess whether the effects of compound 22 were
      mediated through TAAR1, experiments were carried out on TAAR1-KO mice. The
      results showed that compound 22 is able to enhance amphetamine- and cocaine
      mediated locomotor activity, even in TAAR1-KO mice, suggesting that the in vivo
      effects of this compound are not mediated by TAAR1. In collaboration with
      Psychoactive Drug Screening Program, we attempted to determine the targets for
      compound 22. Psychoactive Drug Screening Program (PDSP) results suggested several
      potential targets for compound 22 including, the dopamine, norepinephrine and
      serotonin transporters; as well as sigma 1 and 2 receptors. Our follow-up studies
      using heterologous cell systems showed that the dopamine transporter is not a
      target of compound 22. Therefore, the biological target of compound 22 mediating
      its psychoactive effects still remains unknown.

PMID- 30233367
TI  - Gene Therapy Using Plasmid DNA Encoding VEGF164 and FGF2 Genes: A Novel Treatment
      of Naturally Occurring Tendinitis and Desmitis in Horses.
AB  - This clinical study describes the intralesional application of the plasmid DNA
      encoding two therapeutic species-specific growth factors: vascular endothelial
      growth factor (VEGF164) and fibroblast growth factor 2 (FGF2) in seven horses to
      restore naturally occurring injuries of the superficial digital flexor tendon
      (SDFT) (tendinitis) and in three horses with suspensory ligament branch desmitis.
      Following application all horses were able to commence a more rapid exercise
      program in comparison to standardized exercise programs. Clinical observation and
      ultrasonic imaging was used to evaluate the regeneration rate of the tendon and
      ligament injury recovery and to confirm the safety of this gene therapy in
      horses, throughout a 12 month period. Follow-up data of the horses revealed a
      positive outcome including significant ultrasonographic and clinical improvements
      in 8 out of 10 horses with SDFT and suspensory ligament branch lesions, with
      return to their pre-injury level of performance by 2-6 months after the
      completion of treatment. The ninth horse initially presenting with severe
      suspensory ligament branch desmopathy, showed no significant ultrasonographic
      improvements in the first 2 months after treatment, however, it improved
      clinically and became less lame. The final horse, presenting with severe
      tendinitis of the SDFT returned to their pre-injury level of performance, but
      experienced re-injury 6 months after treatment. This data is highly promising,
      however, further research in experimental models, with the histopathological,
      immunohistochemical and gene expression evaluation of the equine tendon/ligament
      after gene therapy application is required in order to fully understand the
      mechanisms of action. This treatment and the significant clinical impacts
      observed represents an important advancement in the field of medicine.

PMID- 30233366
TI  - Wen-Luo-Tong Decoction Attenuates Paclitaxel-Induced Peripheral Neuropathy by
      Regulating Linoleic Acid and Glycerophospholipid Metabolism Pathways.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting
      toxicity of many anti-neoplastic agents, especially paclitaxel, and oxaliplatin.
      Up to 62% of patients receiving paclitaxel regimens turn out to develop CIPN.
      Unfortunately, there are so few agents proved effective for prevention or
      management of CIPN. The reason for the current situation is that the mechanisms
      of CIPN are still not explicit. Traditional Chinese Medicine (TCM) has unique
      advantages for dealing with complex diseases. Wen-Luo-Tong (WLT) is a TCM
      ointment for topical application. It has been applied for prevention and
      management of CIPN clinically for more than 10 years. Previous animal experiments
      and clinical studies had manifested the availability of WLT. However, due to the
      unclear mechanisms of WLT, further transformation has been restricted. To
      investigate the therapeutic mechanisms of WLT, a metabolomic method on the basis
      of UPLC- MS was developed in this study. Multivariate analysis techniques, such
      as principal component analysis (PCA) and partial least squares discriminate
      analysis (PLS-DA), were applied to observe the disturbance in the metabolic state
      of the paclitaxel-induced peripheral neuropathy (PIPN) rat model, as well as the
      recovering tendency of WLT treatment. A total of 19 significant variations
      associated with PIPN were identified as biomarkers. Results of pathway analysis
      indicated that the metabolic disturbance of pathways of linoleic acid (LA)
      metabolism and glycerophospholipid metabolism. WLT attenuated mechanical
      allodynia and rebalanced the metabolic disturbances of PIPN by primarily
      regulating LA and glycerophospholipid metabolism pathway. Further molecular
      docking analysis showed some ingredients of WLT, such as hydroxysafflor yellow A
      (HSYA), icariin, epimedin B and 4-dihydroxybenzoic acid (DHBA), had high affinity
      to plenty of proteins within these two pathways.

PMID- 30233368
TI  - Optimization of the Linker Length of Mannose-Cholesterol Conjugates for Enhanced
      mRNA Delivery to Dendritic Cells by Liposomes.
AB  - Liposomes (LPs) as commonly used mRNA delivery systems remain to be rationally
      designed and optimized to ameliorate the antigen expression of mRNA vaccine in
      dendritic cells (DCs). In this study, we synthesized mannose-cholesterol
      conjugates (MPn-CHs) by click reaction using different PEG units (PEG100,
      PEG1000, and PEG2000) as linker molecules. MPn-CHs were fully characterized and
      subsequently used to prepare DC-targeting liposomes (MPn-LPs) by a thin-film
      dispersion method. MPn-LPs loaded with mRNA (MPn-LPX) were finally prepared by a
      simple self-assembly method. MPn-LPX displayed bigger diameter (about 135 nm) and
      lower zeta potential (about 40 mV) compared to MPn-LPs. The in vitro transfection
      experiment on DC2.4 cells demonstrated that the PEG length of mannose derivatives
      had significant effect on the expression of GFP-encoding mRNA. MP1000-LPX
      containing MP1000-CH can achieve the highest transfection efficiency (52.09 +/-
      4.85%), which was significantly superior to the commercial transfection reagent
      Lipo 3K (11.47 +/- 2.31%). The optimal DC-targeting MP1000-LPX showed an average
      size of 132.93 +/- 4.93 nm and zeta potential of 37.93 +/- 2.95 mV with nearly
      spherical shape. Moreover, MP1000-LPX can protect mRNA against degradation in
      serum with high efficacy. The uptake study indicated that MP1000-LPX enhanced
      mRNA expression mainly through the over-expressing mannose receptor (CD206) on
      the surface of DCs. In conclusion, mannose modified LPs might be a potential DC
      targeting delivery system for mRNA vaccine after rational design and deserve
      further study on the in vivo delivery profile and anti-tumor efficacy.

PMID- 30233370
TI  - Commentary: Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to
      Enable Recognition Memory.

PMID- 30233369
TI  - Discovery of Potent Disheveled/Dvl Inhibitors Using Virtual Screening Optimized
      With NMR-Based Docking Performance Index.
AB  - Most solid tumors have their own cancer stem cells (CSCs), which are resistant to
      standard chemo-therapies. Recent reports have described that Wnt pathway plays a
      key role in self-renewal and tumorigenesis of CSCs. Regarding the Wnt/beta
      catenin pathway, Dvl (mammalian Disheveled) is an attractive target of drug
      discovery. After analyzing the PDZ domain of human Dvl1 (Dvl1-PDZ) using NMR, we
      subjected it to preliminary NMR titration studies with 17 potential PDZ-binding
      molecules including CalBioChem-322338, a commercially available Dvl PDZ domain
      inhibitor. Next, we performed virtual screening (VS) using the program GOLD with
      nine parameter sets. Results were evaluated using the NMR-derived docking
      performance index (NMR-DPI). One parameter set of GOLD docking showing the best
      NMR-DPI was selected and used for the second VS against 5,135 compounds. The
      second docking trial identified more than 1,700 compounds that exhibited higher
      scores than CalBioChem-322338. Subsequent NMR titration experiments with five new
      candidate molecules (NPL-4001, 4004, 4011, 4012, and 4013), Dvl1-PDZ revealed
      larger chemical shift changes than those of CalBioChem-322338. Finally, these
      compounds showed partial proliferation inhibition activity against BT-20, a
      triple negative breast cancer (TNBC) cell. These compounds are promising Wnt
      pathway inhibitors that are potentially useful for anti-TNBC therapy.

PMID- 30233361
TI  - A History of Drug Discovery for Treatment of Nausea and Vomiting and the
      Implications for Future Research.
AB  - The origins of the major classes of current anti-emetics are examined.
      Serendipity is a recurrent theme in discovery of their anti-emetic properties and
      repurposing from one indication to another is a continuing trend. Notably, the
      discoveries have occurred against a background of company mergers and changing
      anti-emetic requirements. Major drug classes include: (i) Muscarinic receptor
      antagonists-originated from historical accounts of plant extracts containing
      atropine and hyoscine with development stimulated by the need to prevent sea
      sickness among soldiers during beach landings; (ii) Histamine receptor
      antagonists-searching for replacements for the anti-malaria drug quinine, in
      short supply because of wartime shipping blockade, facilitated the discovery of
      histamine (H1) antagonists (e.g., dimenhydrinate), followed by serendipitous
      discovery of anti-emetic activity against motion sickness in a patient undergoing
      treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists
      investigations of their pharmacology as "sedatives" (e.g., chlorpromazine)
      implicated dopamine receptors in emesis, leading to development of selective
      dopamine (D2) receptor antagonists (e.g., domperidone with poor ability to
      penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery;
      (iv) Metoclopramide and selective 5-hydroxytryptamine3(5-HT3) receptor
      antagonists-metoclopramide was initially assumed to act only via D2 receptor
      antagonism but subsequently its gastric motility stimulant effect (proposed to
      contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine4
      receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against
      the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to
      antagonism at 5-HT3 receptors. The latter led to identification of selective 5
      HT3 receptor antagonists (e.g., granisetron), a major breakthrough in treatment
      of chemotherapy-induced emesis; (v) Neurokinin1receptor antagonists-antagonists
      of the actions of substance P were developed as analgesics but pre-clinical
      studies identified broad-spectrum anti-emetic effects; clinical studies showed
      particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally,
      the repurposing of different drugs for treatment of nausea and vomiting is
      examined, particularly during palliative care, and also the challenges in
      identifying novel anti-emetic drugs, particularly for treatment of nausea as
      compared to vomiting. We consider the lessons from the past for the future and
      ask why there has not been a major breakthrough in the last 20 years.

PMID- 30233371
TI  - Neuroprotective Effect of Coumarin Nasal Formulation: Kindling Model Assessment
      of Epilepsy.
AB  - Epilepsy is a brain disorder characterized by sudden recurrent seizures.
      Considering the fact that epileptogenesis is a process that affects the quality
      of life, our goal is to delay the process of epileptogenesis and to increase the
      latency of epileptic attacks, offering better quality of life to patients.
      Traditional system of medicines has a promise in some of the medicines, which
      have been used for the treatment of epilepsy. One such medicinal plant is Eclipta
      alba (EA). According to Ayurvedic philosophy, the juice of leaves of EA is
      pounded with garlic and pepper for the treatment of epilepsy. Taking clue from
      the Ayurvedic system of medicines, we formulated coumarin fraction of EA, namely,
      coumarin nasal formulation (CNF) for its nasal delivery. CNF was analyzed by
      using high performance liquid chromatography (HPLC) and ultraviolet absorption
      spectroscopy for its drug content determination. In vitro drug release studies
      were performed in simulated nasal electrolyte solution (SNES) maintaining
      constant pH of 5.5 at 37 degrees C. Irritation by CNF was evaluated using hen's
      egg test chorioallantoic membrane (HET-CAM) assay. Formulation was found to be
      non-irritant in HET-CAM assay. CNF was further assessed in vivo by measuring the
      progress and attainment of pentylenetetrazole (PTZ) kindling in mice. Neuronal
      changes were assessed by hematoxylin and eosin (H&E) and Nissl staining
      technique. Glial fibrillary acidic protein (GFAP) a neuroinflammatory marker and
      tumor necrosis factor alpha (TNF-alpha) an inflammatory marker were also
      measured. CNF (10 mg/kg, nasal route) when given as a pretreatment lowered
      seizure score and delayed the progression of seizure similar to diazepam. CNF
      decreased the PTZ induced oxidative damage, TNF-alpha as well as GFAP levels in
      the midbrain tissue particularly in hippocampus region. The results suggest that
      CNF may be a promising therapeutic approach to offer protection from sudden
      recurrent seizures alone or in combination with current drugs in management of
      epilepsy.

PMID- 30233372
TI  - LSD Administered as a Single Dose Reduces Alcohol Consumption in C57BL/6J Mice.
AB  - There is a substantive clinical literature on classical hallucinogens, most
      commonly lysergic acid diethylamide (LSD) for the treatment of alcohol use
      disorder. However, there has been no published research on the effect of LSD on
      alcohol consumption in animals. This study evaluated the effect of LSD in mice
      using a two-bottle choice alcohol drinking paradigm. Adult male C57BL/6J mice
      were exposed to ethanol to develop preference and divided into three groups of
      equal ethanol consumption, and then treated with single intraperitoneal injection
      of saline or 25 or 50 MUg/kg LSD and offered water and 20% ethanol. The
      respective LSD-treated groups were compared to the control group utilizing a
      multilevel model for repeated measures. In mice treated with 50 MUg/kg LSD
      ethanol consumption was reduced relative to controls (p = 0.0035), as was ethanol
      preference (p = 0.0024), with a group mean reduction of ethanol consumption of
      17.9% sustained over an interval of 46 days following LSD administration. No
      significant effects on ethanol consumption or preference were observed in mice
      treated with 25 MUg/kg LSD. Neither total fluid intake nor locomotor activity in
      the LSD-treated groups differed significantly from controls. These results
      suggest that classical hallucinogens in the animal model merit further study as a
      potential approach to the identification of targets for drug discovery and
      investigation of the neurobiology of addiction.

PMID- 30233373
TI  - Future Information Technology Tools for Fighting Substandard and Falsified
      Medicines in Low- and Middle-Income Countries.
AB  - Substandard and falsified (SF) medicines have emerged as a global public health
      issue within the last two decades especially in low- and middle-income countries
      (LMICs). Serious consequences of this problem include a loss of trust and
      increased financial costs due to less disease control and more frequent
      complications during therapy. Of note, antimicrobial resistance is an additional
      long-term implication of poor-quality antimicrobials. This review covers
      information technology tools including medicines authentication tools (MAT) as
      mobile apps and messaging service, 2D barcoding approaches with drug safety alert
      systems, web based drug safety alerts, radiofrequency identification tags,
      databases to support visual inspection, digital aids to enhance the performance
      of quality evaluation kits, reference libraries for identification of falsified
      and substandard medicines, and quality evaluation kits based on machine learning
      for field testing. While being easy to access and simple to use, these
      initiatives are gaining acceptance in LMICs. Implementing 2D barcoding based on
      end-to-end verification and "Track and Trace" systems has emerged as a step
      toward global security in the supply chain. A breakthrough in web-based drug
      safety alert systems and data bases was the establishment of the Global
      Surveillance and Monitoring System by the World Health Organization in 2013.
      Future applications include concepts including "lab on a chip" and "paper
      analytical devices" and are claimed to be convenient and simple to use as well as
      affordable. The principles discussed herein are making profound impact in the
      fight against substandard and falsified medicines, offering cheap and accessible
      solutions.

PMID- 30233374
TI  - Subcellular Targeting of Theranostic Radionuclides.
AB  - The last decade has seen rapid growth in the use of theranostic radionuclides for
      the treatment and imaging of a wide range of cancers. Radionuclide therapy and
      imaging rely on a radiolabeled vector to specifically target cancer cells.
      Radionuclides that emit beta particles have thus far dominated the field of
      targeted radionuclide therapy (TRT), mainly because the longer range (MUm-mm
      track length) of these particles offsets the heterogeneous expression of the
      molecular target. Shorter range (nm-MUm track length) alpha- and Auger electron
      (AE)-emitting radionuclides on the other hand provide high ionization densities
      at the site of decay which could overcome much of the toxicity associated with
      beta-emitters. Given that there is a growing body of evidence that other
      sensitive sites besides the DNA, such as the cell membrane and mitochondria,
      could be critical targets in TRT, improved techniques in detecting the
      subcellular distribution of these radionuclides are necessary, especially since
      many beta-emitting radionuclides also emit AE. The successful development of TRT
      agents capable of homing to targets with subcellular precision demands the
      parallel development of quantitative assays for evaluation of spatial
      distribution of radionuclides in the nm-MUm range. In this review, the status of
      research directed at subcellular targeting of radionuclide theranostics and the
      methods for imaging and quantification of radionuclide localization at the
      nanoscale are described.

PMID- 30233375
TI  - Selective Cytotoxicity of Dihydroorotate Dehydrogenase Inhibitors to Human Cancer
      Cells Under Hypoxia and Nutrient-Deprived Conditions.
AB  - Human dihydroorotate dehydrogenase (HsDHODH) is a key enzyme of pyrimidine de
      novo biosynthesis pathway. It is located on the mitochondrial inner membrane and
      contributes to the respiratory chain by shuttling electrons to the ubiquinone
      pool. We have discovered ascofuranone (1), a natural compound produced by
      Acremonium sclerotigenum, and its derivatives are a potent class of HsDHODH
      inhibitors. We conducted a structure-activity relationship study and have
      identified functional groups of 1 that are essential for the inhibition of
      HsDHODH enzymatic activity. Furthermore, the binding mode of 1 and its
      derivatives to HsDHODH was demonstrated by co-crystallographic analysis and we
      show that these inhibitors bind at the ubiquinone binding site. In addition, the
      cytotoxicities of 1 and its potent derivatives 7, 8, and 9 were studied using
      human cultured cancer cells. Interestingly, they showed selective and strong
      cytotoxicity to cancer cells cultured under microenvironment (hypoxia and
      nutrient-deprived) conditions. The selectivity ratio of 8 under this
      microenvironment show the most potent inhibition which was over 1000-fold higher
      compared to that under normal culture condition. Our studies suggest that under
      microenvironment conditions, cancer cells heavily depend on the pyrimidine de
      novo biosynthesis pathway. We also provide the first evidence that 1 and its
      derivatives are potential lead candidates for drug development which target the
      HsDHODH of cancer cells living under a tumor microenvironment.

PMID- 30233377
TI  - In vitro and in vivo Pharmacological Activities of 14-O-Phenylpropyloxymorphone,
      a Potent Mixed Mu/Delta/Kappa-Opioid Receptor Agonist With Reduced Constipation
      in Mice.
AB  - Pain, particularly chronic pain, is still an unsolved medical condition. Central
      goals in pain control are to provide analgesia of adequate efficacy and to reduce
      complications associated with the currently available drugs. Opioids are the
      mainstay for the treatment of moderate to severe pain. However, opioid pain
      medications also cause detrimental side effects, thus highlighting the need of
      innovative and safer analgesics. Opioids mediate their actions via the activation
      of opioid receptors, with the mu-opioid receptor as the primary target for
      analgesia, but also for side effects. One long-standing focus of drug discovery
      is the pursuit for new opioids exhibiting a favorable dissociation between
      analgesia and adverse effects. In this study, we describe the in vitro and in
      vivo pharmacological profiles of the 14-O-phenylpropyl substituted analog of the
      mu-opioid agonist 14-O-methyloxymorphone (14-OMO). The consequence of the
      substitution of the 14-O-methyl in 14-OMO with a 14-O-phenylpropyl group on in
      vitro binding and functional activity, and in vivo behavioral properties
      (nociception and gastrointestinal motility) was investigated. In binding studies,
      14-O-phenylpropyloxymorphone (POMO) displayed very high affinity at mu-, delta-,
      and kappa-opioid receptors (Ki values in nM, mu:delta:kappa = 0.073:0.13:0.30) in
      rodent brain membranes, with complete loss of mu-receptor selectivity compared to
      14-OMO. In guinea-pig ileum and mouse vas deferens bioassays, POMO was a highly
      efficacious and full agonist, being more potent than 14-OMO. In the
      [35S]GTPgammaS binding assays with membranes from CHO cells expressing human
      opioid receptors, POMO was a potent mu/delta-receptor full agonist and a kappa
      receptor partial agonist. In vivo, POMO was highly effective in acute thermal
      nociception (hot-plate test, AD50 = 0.7 nmol/kg) in mice after subcutaneous
      administration, with over 70- and 9000-fold increased potency than 14-OMO and
      morphine, respectively. POMO-induced antinociception is mediated through the
      activation of the mu-opioid receptor, and it does not involve delta- and kappa
      opioid receptors. In the charcoal test, POMO produced fourfold less inhibition of
      the gastrointestinal transit than 14-OMO and morphine. In summary, POMO emerges
      as a new potent mixed mu/delta/kappa-opioid receptor agonist with reduced
      liability to cause constipation at antinociceptive doses.

PMID- 30233378
TI  - Did the New Italian Law on Mandatory Vaccines Affect Adverse Event Following
      Immunization's Reporting? A Pharmacovigilance Study in Southern Italy.
AB  - Despite the well-recognized role of vaccines, coverage is far from optimal
      especially in children, representing a growing concern also in Italy. In order to
      reverse this emergency, the Italian Ministry approved in July 2017 the Law
      119/2017, which renders mandatory and free of charge 10 vaccinations for patients
      aged 0-16. We aim to investigate the effects of the new Law 119/2017 on the
      reporting of adverse events following immunization related to mandatory vaccines
      into the Italian Pharmacovigilance database (Rete Nazionale di Farmacovigilanza -
      RNF). Therefore, we analyzed the spontaneous reports of suspected adverse events
      following immunization recorded in Campania Region (South of Italy) from December
      1, 2016, to March 31, 2018. During the study period, 69 reports, covering 179
      AEFIs, related to mandatory vaccines were sent to Campania Pharmacovigilance
      Regional Center. A substantial increase in AEFIs reporting was observed after the
      adoption of Law 119/2017. Out of 69 reports, 62% reported AEFIs that were
      considered as not serious and 78% had a favorable outcome. Out of 179 AEFIs, more
      than half referred to the following SOC: "general disorders and administration
      site conditions," "nervous system disorders," and "psychiatric disorders." The
      highest number of reports came from patient/citizen. After the adoption of the
      Law 119/2017, there was an increase in the number of reports (18 before the
      adoption of the Law vs. 51 after). According to reported AEFIs during the entire
      period, no worrying safety data have emerged. In our opinion, the increase in the
      number of AEFIs' reports should be related to the increase in vaccination
      coverage as well as to the intense debate that has followed the new Law. In this
      context, the continuous monitoring of vaccine safety and the fully implementation
      of vaccine-vigilance programs play a key role in achieving higher confidence in
      immunization programs and optimal vaccination coverage rate.

PMID- 30233376
TI  - The NaV1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in
      Adult Dorsal Root Ganglia Neurons.
AB  - Although necessary for human survival, pain may sometimes become pathologic if
      long-lasting and associated with alterations in its signaling pathway. Opioid
      painkillers are officially used to treat moderate to severe, and even mild, pain.
      However, the consequent strong and not so rare complications that occur,
      including addiction and overdose, combined with pain management costs, remain an
      important societal and economic concern. In this context, animal venom toxins
      represent an original source of antinociceptive peptides that mainly target ion
      channels (such as ASICs as well as TRP, CaV, KV and NaV channels) involved in
      pain transmission. The present review aims to highlight the NaV1.7 channel
      subtype as an antinociceptive target for spider toxins in adult dorsal root
      ganglia neurons. It will detail (i) the characteristics of these primary sensory
      neurons, the first ones in contact with pain stimulus and conveying the
      nociceptive message, (ii) the electrophysiological properties of the different
      NaV channel subtypes expressed in these neurons, with a particular attention on
      the NaV1.7 subtype, an antinociceptive target of choice that has been validated
      by human genetic evidence, and (iii) the features of spider venom toxins, shaped
      of inhibitory cysteine knot motif, that present high affinity for the NaV1.7
      subtype associated with evidenced analgesic efficacy in animal models.

PMID- 30233380
TI  - Therapeutic Effects of Wenxin Keli in Cardiovascular Diseases: An Experimental
      and Mechanism Overview.
AB  - Cardiovascular diseases (CVDs) are the major public health problem and a leading
      cause of morbidity and mortality on a global basis. Wenxin Keli (WXKL), a
      formally classical Chinese patent medicine with obvious efficacy and favorable
      safety, plays a great role in the management of patients with CVDs. Accumulating
      evidence from various animal and cell studies has showed that WXKL could protect
      myocardium and anti-arrhythmia against CVDs. WXKL exhibited its cardioprotective
      roles by inhibiting inflammatory reaction, decreasing oxidative stress,
      regulating vasomotor disorders, lowering cell apoptosis, and protection against
      endothelial injure, myocardial ischemia, cardiac fibrosis, and cardiac
      hypertrophy. Besides, WXKL could effectively shorten the QRS and Q-T intervals,
      decrease the incidence of atrial/ventricular fibrillation and the number of
      ventricular tachycardia episodes, improve the severity of arrhythmias by
      regulating various ion channels with different potencies, mainly comprising peak
      sodium current (INa), late sodium current (INaL), transient outward potassium
      current (Ito), L-type calcium current (ICaL), and pacemaker current (If).

PMID- 30233379
TI  - Evaluation of Oral Antiretroviral Drugs in Mice With Metabolic and Neurologic
      Complications.
AB  - Antiretroviral (ART) drugs has previously been associated with lipodystrophic
      syndrome, metabolic consequences, and neuropsychiatric complications. ART drugs
      include three main classes of protease inhibitors (PIs), nucleoside analog
      reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse
      transcriptase inhibitors (NNRTIs). Our previous work demonstrated that a high
      risk of hyperlipidemia was observed in HIV-1-infected patients who received ART
      drugs in Taiwan. Patients receiving ART drugs containing either
      Abacavir/Lamivudine (Aba/Lam; NRTI/NRTI), Lamivudine/Zidovudine (Lam/Zido;
      NRTI/NRTI), or Lopinavir/Ritonavir (Lop/Rit; PI) have the highest risk of
      hyperlipidemia. The aim of this study was to investigate the effects of Aba/Lam
      (NRTI/NRTI), Lam/Zido (NRTI/NRTI), and Lop/Rit (PI) on metabolic and neurologic
      functions in mice. Groups of C57BL/6 mice were administered Aba/Lam, Lam/Zido, or
      Lop/Rit, orally, once daily for a period of 4 weeks. The mice were then
      extensively tested for metabolic and neurologic parameters. In addition, the
      effect of Aba/Lam, Lam/Zido, and Lop/Rit on lipid metabolism was assessed in
      HepG2 hepatocytes and during the 3T3-L1 preadipocyte differentiation.
      Administration with Aba/Lam caused cognitive and motor impairments in mice, as
      well as their metabolic imbalances, including alterations in leptin serum levels.
      Administration with Lop/Rit also caused cognitive and motor impairments in mice,
      as well as their metabolic imbalances, including alterations in serum levels of
      total cholesterol, and HDL-c. Treatment of mice with Aba/Lam and Lop/Rit enhanced
      the lipid accumulation in the liver, and the decrease in AMP-activated protein
      kinase (AMPK) phosphorylation and/or its downstream target acetyl-CoA carboxylase
      (ACC) protein expression. In HepG2 hepatocytes, Aba/Lam, Lam/Zido, and Lop/Rit
      also enhanced the lipid accumulation and decreased phosphorylated AMPK and ACC
      proteins. In 3T3-L1 pre-adipocyte differentiation, Aba/Lam and Lop/Rit reduced
      adipogenesis by decreasing expression of transcription factor CEBPb, implicating
      the lipodystrophic syndrome. Our results demonstrate that daily oral
      administration of Aba/Lam and Lop/Rit may produce cognitive, motor, and metabolic
      impairments in mice, regardless of HIV-1 infection.

PMID- 30233381
TI  - The Resting Potential and K+ Currents in Primary Human Articular Chondrocytes.
AB  - Human transplant programs provide significant opportunities for detailed in vitro
      assessments of physiological properties of selected tissues and cell types. We
      present a semi-quantitative study of the fundamental
      electrophysiological/biophysical characteristics of human chondrocytes, focused
      on K+ transport mechanisms, and their ability to regulate to the resting membrane
      potential, Em. Patch clamp studies on these enzymatically isolated human
      chondrocytes reveal consistent expression of at least three functionally distinct
      K+ currents, as well as transient receptor potential (TRP) currents. The small
      size of these cells and their exceptionally low current densities present
      significant technical challenges for electrophysiological recordings. These
      limitations have been addressed by parallel development of a mathematical model
      of these K+ and TRP channel ion transfer mechanisms in an attempt to reveal their
      contributions to Em. In combination, these experimental results and simulations
      yield new insights into: (i) the ionic basis for Em and its expected range of
      values; (ii) modulation of Em by the unique articular joint extracellular milieu;
      (iii) some aspects of TRP channel mediated depolarization-secretion coupling;
      (iv) some of the essential biophysical principles that regulate K+ channel
      function in "chondrons." The chondron denotes the chondrocyte and its immediate
      extracellular compartment. The presence of discrete localized surface charges and
      associated zeta potentials at the chondrocyte surface are regulated by cell
      metabolism and can modulate interactions of chondrocytes with the extracellular
      matrix. Semi-quantitative analysis of these factors in chondrocyte/chondron
      function may yield insights into progressive osteoarthritis.

PMID- 30233384
TI  - Heart Rate Fragmentation as a Novel Biomarker of Adverse Cardiovascular Events:
      The Multi-Ethnic Study of Atherosclerosis.
AB  - Background: A major objective of precision medicine is the elucidation of non
      invasive biomarkers of cardiovascular (CV) risk. Recently, we introduced a new
      dynamical marker of sino-atrial instability, termed heart rate fragmentation
      (HRF), which outperformed traditional and nonlinear heart rate variability
      metrics in separating ostensibly healthy subjects from patients with coronary
      artery disease. Accordingly, we hypothesized that HRF may be a dynamical
      biomarker of adverse cardiovascular events (CVEs). Methods: This study employed
      data from a cohort of participants in the Multi-Ethnic Study of Atherosclerosis
      (MESA), a prospective study of sub-clinical heart disease. Interbeat interval
      time series (n = 1963), derived from the electrocardiographic channel of the
      polysomnogram study, were analyzed using the newly introduced metrics of
      fragmentation, as well as traditional heart rate variability (HRV) indices and
      the short-term detrended fluctuation analysis exponent. Cox regression analysis
      was used to assess the association between HR dynamic indices and CV outcomes in
      unadjusted and adjusted models. Results: The mean (+/- SD) follow-up time was
      2.97 +/- 0.63 years. In adjusted models, higher fragmentation was significantly
      associated with incident CVEs (number of events; hazard ratio [95% confidence
      interval]: n = 72, 1.43 [1.16-1.76]) and CV death (n = 21; 1.65 [1.15-2.36]). The
      traditional HRV and the fractal indices were not associated with CVEs or CV
      death. The most discriminatory fragmentation indices added significant value to
      Framingham and MESA CV risk indices in all analyses. Conclusion: Our findings
      show that HRF has promise as a non-invasive, automatable biomarker of CV risk.
      The basic mechanisms underlying fragmentation remain to be delineated. Its
      association with incident outcomes raises the possibility of connections to
      degenerative changes in the multisystem network controlling SAN function.

PMID- 30233385
TI  - Electrocardiographic Imaging Using a Spatio-Temporal Basis of Body Surface
      Potentials-Application to Atrial Ectopic Activity.
AB  - Electrocardiographic imaging (ECGI) strongly relies on a priori assumptions and
      additional information to overcome ill-posedness. The major challenge of
      obtaining good reconstructions consists in finding ways to add information that
      effectively restricts the solution space without violating properties of the
      sought solution. In this work, we attempt to address this problem by constructing
      a spatio-temporal basis of body surface potentials (BSP) from simulations of many
      focal excitations. Measured BSPs are projected onto this basis and
      reconstructions are expressed as linear combinations of corresponding
      transmembrane voltage (TMV) basis vectors. The novel method was applied to
      simulations of 100 atrial ectopic foci with three different conduction
      velocities. Three signal-to-noise ratios (SNR) and bases of six different
      temporal lengths were considered. Reconstruction quality was evaluated using the
      spatial correlation coefficient of TMVs as well as estimated local activation
      times (LAT). The focus localization error was assessed by computing the geodesic
      distance between true and reconstructed foci. Compared with an optimally
      parameterized Tikhonov-Greensite method, the BSP basis reconstruction increased
      the mean TMV correlation by up to 22, 24, and 32% for an SNR of 40, 20, and 0 dB,
      respectively. Mean LAT correlation could be improved by up to 5, 7, and 19% for
      the three SNRs. For 0 dB, the average localization error could be halved from
      15.8 to 7.9 mm. For the largest basis length, the localization error was always
      below 34 mm. In conclusion, the new method improved reconstructions of atrial
      ectopic activity especially for low SNRs. Localization of ectopic foci turned out
      to be more robust and more accurate. Preliminary experiments indicate that the
      basis generalizes to some extent from the training data and may even be applied
      for reconstruction of non-ectopic activity.

PMID- 30233382
TI  - Oxidative Stress in the Blood Labyrinthine Barrier in the Macula Utricle of
      Meniere's Disease Patients.
AB  - The blood labyrinthine barrier (BLB) is critical in the maintenance of inner ear
      ionic and fluid homeostasis. Recent studies using imaging and histopathology
      demonstrate loss of integrity of the BLB in the affected inner ear of Meniere's
      disease (MD) patients. We hypothesized that oxidative stress is involved in the
      pathogenesis of BLB degeneration, and to date there are no studies of oxidative
      stress proteins in the human BLB. We investigated the ultrastructural and
      immunohistochemical changes of the BLB in the vestibular endorgan, the macula
      utricle, from patients with MD (n = 10), acoustic neuroma (AN) (n = 6) and
      normative autopsy specimens (n = 3) with no inner ear disease. Each subject had a
      well-documented clinical history and audiovestibular testing. Utricular maculae
      were studied using light and transmission electron microscopy and double labeling
      immunofluorescence. Vascular endothelial cells (VECs) were identified using
      isolectin B4 (IB4) and glucose-transporter-1 (GLUT-1). Pericytes were identified
      using alpha smooth muscle actin (alphaSMA) and phalloidin. IB4 staining of VECS
      was consistently seen in both AN and normative. In contrast, IB4 was nearly
      undetectable in all MD specimens, consistent with the significant VEC damage
      confirmed on transmission electron microscopy. GLUT-1 was present in MD, AN, and
      normative. alphaSMA and phalloidin were expressed consistently in the BLB
      pericytes in normative, AN specimen, and Meniere's specimens. Endothelial nitric
      oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and nitrotyrosine
      were used as markers of oxidative stress. The VECs of the BLB in Meniere's had
      significantly higher levels of expression of iNOS and nitrotyrosine compared with
      normative and AN specimen. eNOS-IF staining showed similar patterns in normative
      and Meniere's specimens. Microarray-based gene expression profiling confirmed
      upregulation of iNOS mRNA from the macula utricle of Meniere's patients compared
      with AN. Nitrotyrosine, a marker recognized as a hallmark of inflammation,
      especially when seen in association with an upregulation of iNOS, was detected in
      the epithelial and stromal cells in addition to VECs in MD. Immunohistochemical
      and ultrastructural degenerative changes of the VEC suggest that these cells are
      the primary targets of oxidative stress, and pericyte pathology including
      degeneration and migration, likely also plays a role in the loss of integrity of
      the BLB and triggering of inflammatory pathways in MD. These studies advance our
      scientific understanding of oxidative stress in the human inner ear BLB and
      otopathology.

PMID- 30233383
TI  - Benfotiamine, a Lipid-Soluble Analog of Vitamin B1, Improves the Mitochondrial
      Biogenesis and Function in Blunt Snout Bream (Megalobrama amblycephala) Fed High
      Carbohydrate Diets by Promoting the AMPK/PGC-1beta/NRF-1 Axis.
AB  - This study evaluated the effects of benfotiamine on the growth performance and
      mitochondrial biogenesis and function in Megalobrama amblycephala fed high
      carbohydrate (HC) diets. The fish (45.25 +/- 0.34 g) were randomly fed six diets:
      the control diet (30% carbohydrate, C), the HC diet (43% carbohydrate), and the
      HC diet supplemented with different benfotiamine levels (0.7125 (HCB1), 1.425
      (HCB2), 2.85 (HCB3), and 5.7 (HCB4) mg/kg) for 12 weeks. High-carbohydrate levels
      remarkably decreased the weight gain rate (WGR), specific growth rate (SGR),
      relative feed intake (RFI), feed conversion ratio (FCR), p-adenosine
      monophosphate (AMP)-activated protein kinase (AMPK)alpha/t-AMPKalpha ratio,
      peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta)
      and nuclear respiratory factor-1 (NRF-1) protein expression, complexes I, III,
      and IV activities, and hepatic transcriptions of cytochrome b (CYT-b) and
      cytochrome c oxidase-2 (COX-2), whereas the opposite was true for plasma glucose,
      glycated serum protein, advanced glycation end product and insulin levels, tissue
      glycogen and lipid contents, hepatic adenosine triphosphate (ATP) and AMP
      contents and ATP/AMP ratio, complexes V activities, and the expressions of
      AMPKalpha-2, PGC-1beta, NRF-1, mitochondrial transcription factor A (TFAM),
      mitofusin-1 (Mfn-1), optic atrophy-1 (Opa-1), dynamin-related protein-1 (Drp-1),
      fission-1 (Fis-1), mitochondrial fission factor (Mff), and ATP synthase-6 (ATP
      6). As with benfotiamine supplementation, the HCB2 diet remarkably increased WGR,
      SGR, tissue glycogen and lipid contents, AMP content, p-AMPKalpha/t-AMPKalpha
      ratio, PGC-1beta and NRF-1 levels, complexes I, III, IV, and V activities, and
      hepatic transcriptions of AMPKalpha-2, PGC-1beta, NRF-1, TFAM, Mfn-1, Opa-1, CYT
      b, COX-2, and ATP-6, while the opposite was true for the remaining indicators.
      Overall, 1.425 mg/kg benfotiamine improved the growth performance and
      mitochondrial biogenesis and function in fish fed HC diets by the activation of
      the AMPK/PGC-1beta/NRF-1 axis and the upregulation of the activities and
      transcriptions of mitochondrial complexes as well as the enhancement of
      mitochondrial fusion coupled with the depression of mitochondrial fission.

PMID- 30233387
TI  - Tendinous Tissue Adaptation to Explosive- vs. Sustained-Contraction Strength
      Training.
AB  - The effect of different strength training regimes, and in particular training
      utilizing brief explosive contractions, on tendinous tissue properties is poorly
      understood. This study compared the efficacy of 12 weeks of knee extensor
      explosive-contraction (ECT; n = 14) vs. sustained-contraction (SCT; n = 15)
      strength training vs. a non-training control (n = 13) to induce changes in
      patellar tendon and knee extensor tendon-aponeurosis stiffness and size (patellar
      tendon, vastus-lateralis aponeurosis, quadriceps femoris muscle) in healthy young
      men. Training involved 40 isometric knee extension contractions (three
      times/week): gradually increasing to 75% of maximum voluntary torque (MVT) before
      holding for 3 s (SCT), or briefly contracting as fast as possible to ~80% MVT
      (ECT). Changes in patellar tendon stiffness and Young's modulus, tendon
      aponeurosis complex stiffness, as well as quadriceps femoris muscle volume,
      vastus-lateralis aponeurosis area and patellar tendon cross-sectional area were
      quantified with ultrasonography, dynamometry, and magnetic resonance imaging. ECT
      and SCT similarly increased patellar tendon stiffness (20% vs. 16%, both p < 0.05
      vs. control) and Young's modulus (22% vs. 16%, both p < 0.05 vs. control). Tendon
      aponeurosis complex high-force stiffness increased only after SCT (21%; p <
      0.02), while ECT resulted in greater overall elongation of the tendon-aponeurosis
      complex. Quadriceps muscle volume only increased after sustained-contraction
      training (8%; p = 0.001), with unclear effects of strength training on
      aponeurosis area. The changes in patellar tendon cross-sectional area after
      strength training were not appreciably different to control. Our results suggest
      brief high force muscle contractions can induce increased free tendon stiffness,
      though SCT is needed to increase tendon-aponeurosis complex stiffness and muscle
      hypertrophy.

PMID- 30233386
TI  - Bringing the Nonlinearity of the Movement System to Gestural Theories of Language
      Use: Multifractal Structure of Spoken English Supports the Compensation for
      Coarticulation in Human Speech Perception.
AB  - Coarticulation is the tendency for speech vocalization and articulation even at
      the phonemic level to change with context, and compensation for coarticulation
      (CfC) reflects the striking human ability to perceive phonemic stability despite
      this variability. A current controversy centers on whether CfC depends on
      contrast between formants of a speech-signal spectrogram-specifically, contrast
      between offset formants concluding context stimuli and onset formants opening the
      target sound-or on speech-sound variability specific to the coordinative movement
      of speech articulators (e.g., vocal folds, postural muscles, lips, tongues). This
      manuscript aims to encode that coordinative-movement context in terms of speech
      signal multifractal structure and to determine whether speech's multifractal
      structure might explain the crucial gestural support for any proposed spectral
      contrast. We asked human participants to categorize individual target stimuli
      drawn from an 11-step [ga]-to-[da] continuum as either phonemes "GA" or "DA."
      Three groups each heard a specific-type context stimulus preceding target
      stimuli: either real-speech [al] or [a], sine-wave tones at the third-formant
      offset frequency of either [al] or [ar], and either simulated-speech contexts
      [al] or [ar]. Here, simulating speech contexts involved randomizing the sequence
      of relatively homogeneous pitch periods within vowel-sound [a] of each [al] and
      [ar]. Crucially, simulated-speech contexts had the same offset and extremely
      similar vowel formants as and, to additional naive participants, sounded
      identical to real-speech contexts. However, randomization distorted original
      speech-context multifractality, and effects of spectral contrast following speech
      only appeared after regression modeling of trial-by-trial "GA" judgments
      controlled for context-stimulus multifractality. Furthermore, simulated-speech
      contexts elicited faster responses (like tone contexts do) and weakened known
      biases in CfC, suggesting that spectral contrast depends on the nonlinear
      interactions across multiple scales that articulatory gestures express through
      the speech signal. Traditional mouse-tracking behaviors measured as participants
      moved their computer-mouse cursor to register their "GA"-or-"DA" decisions with
      mouse-clicks suggest that listening to speech leads the movement system to
      resonate with the multifractality of context stimuli. We interpret these results
      as shedding light on a new multifractal terrain upon which to found a better
      understanding in which movement systems play an important role in shaping how
      speech perception makes use of acoustic information.

PMID- 30233388
TI  - Normal Values of Myocardial Deformation Assessed by Cardiovascular Magnetic
      Resonance Feature Tracking in a Healthy Chinese Population: A Multicenter Study.
AB  - Reference values on atrial and ventricular strain from cardiovascular magnetic
      resonance (CMR) are essential in identifying patients with impaired atrial and
      ventricular function. However, reference values have not been established for
      Chinese subjects. One hundred and fifty healthy volunteers (75 Males/75 Females;
      18-82 years) were recruited. All underwent CMR scans with images acceptable for
      further strain analysis. Subjects were stratified by age: Group 1, 18-44 years;
      Group 2, 45-59 years; Group 3, >=60 years. Feature tracking of CMR cine imaging
      was used to obtain left atrial global longitudinal (LA Ell) and circumferential
      strains (LA Ecc) and respective systolic strain rates, left ventricular
      longitudinal (LV Ell), circumferential (LV Ecc) and radial strains (LV Err) and
      their respective strain rates, and right ventricular longitudinal strain (RV Ell)
      and strain rate. LA Ell and LA Ecc were 32.8 +/- 9.2% and 40.3 +/- 13.4%,
      respectively, and RV Ell was -29.3 +/- 6.0%. LV Ell, LV Ecc and LV Err were -22.4
      +/- 2.9%, -24.3 +/- 3.1%, and 79.0 +/- 19.4%, respectively. LV Ell and LV Ecc
      were higher in females than males (P < 0.05). LA Ell, LA Ecc, and LV Ecc
      decreased, while LV Err increased with age (P < 0.05). LV Ell and RV Ell were not
      shown to be associated with age. Normal ranges for atrial and ventricular strain
      and strain rates are provided using CMR feature tracking in Chinese subjects.

PMID- 30233389
TI  - Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase
      Inhibitor in a Murine Model of Asthma.
AB  - Background: Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role
      in regulating the expression of inflammatory mediators, immune cell recruitment,
      hyper-responsiveness, tissue remodeling, and oxidative stress. Modulation of IL
      17 and ROCK proteins may represent a promising approach for the treatment of this
      disease. Objective: To study the effects of an anti-IL17 neutralizing antibody
      and ROCK inhibitor treatments, separately and in combination, in a murine model
      of chronic allergy-induced lung inflammation. Methods: Sixty-four BALBc mice,
      were divided into eight groups (n = 8): SAL (saline-instilled); OVA (exposed
      ovalbumin); SAL-RHOi (saline and ROCK inhibitor), OVA-RHOi (exposed-ovalbumin and
      ROCK inhibitor); SAL-anti-IL17 (saline and anti-IL17); OVA-anti-IL17 (exposed
      ovalbumin and anti-IL17); SAL-RHOi-anti-IL17 (saline, ROCK inhibitor and anti
      IL17); and OVA-RHOi-anti-IL17 (exposed-ovalbumin, anti-IL17, and ROCK inhibitor).
      A 28-day protocol of albumin treatment was used for sensitization and induction
      of pulmonary inflammation. The anti-IL17A neutralizing antibody (7.5 MUg per
      treatment) was administered by intraperitoneal injection and ROCK inhibitor (Y
      27632) intranasally (10 mg/kg), 1 h prior to each ovalbumin challenge (days 22,
      24, 26, and 28). Results: Treatment with the anti-IL17 neutralizing antibody and
      ROCK inhibitor attenuated the percentage of maximal increase of respiratory
      system resistance and respiratory system elastance after challenge with
      methacholine and the inflammatory response markers evaluated (CD4+, CD8+, ROCK1,
      ROCK2, IL-4, IL-5, IL-6, IL-10 IL-13, IL-17, TNF-alpha, TGF-beta, NF-kappaB,
      dendritic cells, iNOS, MMP-9, MMP-12, TIMP-1, FOXP3, isoprostane, biglycan,
      decorin, fibronectin, collagen fibers content and gene expression of IL-17,
      VAChT, and arginase) compared to the OVA group (p < 0.05). Treatment with anti
      IL17 and the ROCK inhibitor together resulted in potentiation in decreasing the
      percentage of resistance increase after challenge with methacholine, decreased
      the number of IL-5 positive cells in the airway, and reduced, IL-5, TGF-beta,
      FOXP3, ROCK1 and ROCK2 positive cells in the alveolar septa compared to the OVA
      RHOi and OVA-anti-IL17 groups (p < 0.05). Conclusion: Anti-IL17 treatment alone
      or in conjunction with the ROCK inhibitor, modulates airway responsiveness,
      inflammation, tissue remodeling, and oxidative stress in mice with chronic
      allergic lung inflammation.

PMID- 30233390
TI  - Identification of Biologically Essential Nodes via Determinative Power in Logical
      Models of Cellular Processes.
AB  - A variety of biological networks can be modeled as logical or Boolean networks.
      However, a simplification of the reality to binary states of the nodes does not
      ease the difficulty of analyzing the dynamics of large, complex networks, such as
      signal transduction networks, due to the exponential dependence of the state
      space on the number of nodes. This paper considers a recently introduced method
      for finding a fairly small subnetwork, representing a collection of nodes that
      determine the states of most other nodes with a reasonable level of entropy. The
      subnetwork contains the most determinative nodes that yield the highest
      information gain. One of the goals of this paper is to propose an algorithm for
      finding a suitable subnetwork size. The information gain is quantified by the so
      called determinative power of the nodes, which is obtained via the mutual
      information, a concept originating in information theory. We find the most
      determinative nodes for 36 network models available in the online database Cell
      Collective (http://cellcollective.org). We provide statistical information that
      indicates a weak correlation between the subnetwork size and other variables,
      such as network size, or maximum and average determinative power of nodes. We
      observe that the proportion represented by the subnetwork in comparison to the
      whole network shows a weak tendency to decrease for larger networks. The
      determinative power of nodes is weakly correlated to the number of outputs of a
      node, and it appears to be independent of other topological measures such as
      closeness or betweenness centrality. Once the subnetwork of the most
      determinative nodes is identified, we generate a biological function analysis of
      its nodes for some of the 36 networks. The analysis shows that a large fraction
      of the most determinative nodes are essential and involved in crucial biological
      functions. The biological pathway analysis of the most determinative nodes shows
      that they are involved in important disease pathways.

PMID- 30233392
TI  - FGF10 Is Required for Circumvallate Papilla Morphogenesis by Maintaining Lgr5
      Activity.
AB  - Taste buds develop in different regions of the mammal oral cavity. Adult stem
      cells in various organs including the tongue papillae are marked by leucine-rich
      repeat-containing G protein-coupled receptor 5 (Lgr5) and its homolog, Lgr6.
      Recent studies have reported that adult taste stem/progenitor cells in
      circumvallate papilla (CVP) on the posterior tongue are Lgr5-positive. In this
      study, we confirm the Lgr5 expression pattern during CVP development. A previous
      study reported that mesenchymal Fgf10 is necessary for maintaining epithelial
      Lgr5-positive stem/progenitor cells. To confirm the interaction between Lgr5
      positive CVP epithelium and mesenchymal factor FGF10, reverse recombination (180
      degree) was performed after tongue epithelium detachment. FGF10 protein-soaked
      bead implantation was performed after reverse recombination to rescue CVP
      development. Moreover, we reduced mesenchymal Fgf10 by BIO and SU5402 treatment
      which disrupted CVP morphogenesis. This study suggests that the crosstalk between
      epithelial Lgr5 and mesenchymal Fgf10 plays a pivotal role in CVP epithelium
      invagination during mouse tongue CVP development by maintaining Lgr5-positive
      stem/progenitor cells.

PMID- 30233391
TI  - The NF-kappaB Inhibitor, IMD-0354, Affects Immune Gene Expression, Bacterial
      Microbiota and Trypanosoma cruzi Infection in Rhodnius prolixus Midgut.
AB  - Rhodnius prolixus is an insect vector of Trypanosoma cruzi, the causative agent
      of Chagas disease in Latin America. Nuclear factor-kappaB (NF-kappaB)
      transcription factors (TF) are conserved components of the innate immune system
      in several multicellular organisms including insects. The drug IMD-0354 [N-(3,5
      bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide] is a selective
      inhibitor of IkappaB kinases. It blocks IkappaBalpha phosphorylation thus
      preventing nuclear translocation of the NF-kappab TF. In humans, NF-kappaB is
      involved in several biological processes such as inflammation, cell proliferation
      and immunity. In insects, the activation of the immune system upon microbial
      challenge can be controlled by signaling pathways such as the immune deficiency
      (IMD) and Toll, to combat infection. These activated pathways signal to
      downstream NF-kappaB TF to stimulate specific immune genes, triggering the
      synthesis of several molecules such as the antimicrobial peptides. In Drosophila
      melanogaster, the activation and regulation of NF-kappaB TF have been elucidated,
      while in triatomines these mechanisms are not fully understood Therefore, the
      present study investigated the effects of oral administration of the drug IMD
      0354 on the R. prolixus immune response to challenge with bacteria and T. cruzi,
      as well as the impact on the gut bacterial microbiota. R. prolixus were fed with
      rabbit blood containing IMD-0354 and Escherichia coli, Staphylococcus aureus, or
      T. cruzi. The effects of IMD-0354 on insect mortality and antimicrobial activity
      in insect midgut samples, as well as the relative expression of R. prolixus
      immune genes were recorded. The bacterial microbiota was analyzed, and viable
      parasites were counted in insect midgut samples. The IMD-0354 treatment modulated
      antibacterial activity and the gene expression patterns of defensin A, defensin
      B, defensin C, and prolixicin, and the genes involved in the IMD and Toll
      pathways. Additionally, there was an increase of bacterial microbiota in treated
      insects. Insects treated with IMD-0354 and concomitantly infected with bacteria
      or T. cruzi through the blood meal had increased mortality, while the T. cruzi
      population in R. prolixus midgut was reduced. The inhibitory effect of IMD-0354
      indicates the importance of NF-kappaB TF in the innate immune responses involved
      in the control of bacteria and parasite infections in the R. prolixus midgut.

PMID- 30233394
TI  - Loss of Side-to-Side Connections Affects the Relative Contributions of the Sodium
      and Calcium Current to Transverse Propagation Between Strands of Atrial Myocytes.
AB  - Background: Atrial fibrillation (AF) leads to a loss of transverse connections
      between myocyte strands that is associated with an increased complexity and
      stability of AF. We have explored the interaction between longitudinal and
      transverse coupling, and the relative contribution of the sodium (INa) and
      calcium (ICa) current to propagation, both in healthy tissue and under diseased
      conditions using computer simulations. Methods: Two parallel strands of atrial
      myocytes were modeled (Courtemanche et al. ionic model). As a control condition,
      every single cell was connected both transversely and longitudinally. To simulate
      a loss of transverse connectivity, this number was reduced to 1 in 4, 8, 12, or
      16 transversely. To study the interaction with longitudinal coupling, anisotropy
      ratios of 3, 9, 16, and 25:1 were used. All simulations were repeated for varying
      degrees of INa and ICa block and the transverse activation delay (TAD) between
      the paced and non-paced strands was calculated for all cases. Results: The TAD
      was highly sensitive to the transverse connectivity, increasing from 1 ms at 1 in
      1, to 25 ms at 1 in 4, and 100 ms at 1 in 12 connectivity. The TAD also increased
      when longitudinal coupling was increased. Both decreasing transverse connectivity
      and increasing longitudinal coupling enhanced the synchronicity of activation of
      the non-paced strand and increased the propensity for transverse conduction
      block. Even after long TADs, the action potential upstroke in the non-paced
      strand was still mainly dependent on the INa. Nevertheless, ICa in the paced
      strand was essential to provide depolarizing current to the non-paced strand.
      Loss of transverse connections increased the sensitivity to both INa and ICa
      block. However, when longitudinal coupling was relatively high, transverse
      propagation was more sensitive to ICa block than to INa block. Conclusions:
      Although transverse propagation depends on both INa and ICa, their relative
      contribution, and sensitivity to channel blockade, depends on the distribution of
      transverse connections and the axial conductivity. This simple two-strand model
      helps to explain the nature of atrial discontinuous conduction during structural
      remodeling and provides an opportunity for more effective drug development.

PMID- 30233393
TI  - Physiological and Pathophysiological Relevance of the Anion Transporter Slc26a9
      in Multiple Organs.
AB  - Transepithelial Cl- and HCO3- transport is crucial for the function of all
      epithelia, and HCO3- is a biological buffer that maintains acid-base homeostasis.
      In most epithelia, a series of Cl-/HCO3- exchangers and Cl- channels that mediate
      Cl- absorption and HCO3- secretion have been detected in the luminal and
      basolateral membranes. Slc26a9 belongs to the solute carrier 26 (Slc26) family of
      anion transporters expressed in the epithelia of multiple organs. This review
      summarizes the expression pattern and functional diversity of Slc26a9 in
      different systems based on all investigations performed thus far. Furthermore,
      the physical and functional interactions between Slc26a9 and cystic fibrosis
      transmembrane conductance regulator (CFTR) are discussed due to their overlapping
      expression pattern in multiple organs. Finally, we focus on the relationship
      between slc26a9 mutations and disease onset. An understanding of the
      physiological and pathophysiological relevance of Slc26a9 in multiple organs
      offers new possibilities for disease therapy.

PMID- 30233395
TI  - Automated Spatial Pattern Analysis for Identification of Foot Arch Height From 2D
      Foot Prints.
AB  - Arch height is an important determinant for the risk of foot pathology,
      especially in an aging population. Current methods for analyzing footprints
      require substantial manual processing time. The current research investigated
      automated determination of foot type based on features derived from the Gabor
      wavelet utilizing digitized footprints to allow timely assessment of foot type
      and focused intervention. Two hundred and eighty footprints were collected, and
      area, perimeter, curvature, circularity, 2nd wavelet moment, mean bending energy
      (MBE), and entropy were determined using in house developed MATLAB codes. The
      results were compared to the gold standard using Spearman's Correlation
      coefficient and multiple linear regression models with significance set at 0.05.
      The proposed approach found MBE combined with foot perimeter to give the best
      results as shown by ANOVA (F(2,211) = 10.18, p < 0.0001) with the mean +/-SD of
      low, normal, and high arch being, respectively, 0.26 +/- 0.025,.24 +/- 0.021, and
      0.23 +/- 0.024. A clinical review of the new cut off values, as set by the first
      and the third quartiles of our sample, lead to reliability up to 87%. Our results
      suggest that automated wavelet-based foot type classification of 2D binary images
      of the plantar surface of the foot is comparable to current state-of-the-art
      methods providing a cost and time effective tool suitable for clinical
      diagnostics.

PMID- 30233396
TI  - Vitamin C Intake and Risk of Prostate Cancer: The Montreal PROtEuS Study.
AB  - Background: Vitamin C is a reducing agent and free radical scavenger, acting as
      antioxidant in plasma membranes and within cells. Based on these properties, a
      role for vitamin C in cancer incidence has been suspected. There are as yet few
      large population-based studies focusing on prostate cancer, with the preponderant
      evidence leaning toward the absence of an association. Nevertheless, many
      previous studies overlooked prostate cancer aggressiveness, as well as screening
      and detection issues, which could bias potential associations. Methods: The
      Prostate Cancer and Environment Study (PROtEuS) is a population-based case
      control study conducted in Montreal, Canada. In-person interviews, conducted with
      1,916 histologically confirmed prostate cancer cases and 1,985 population
      controls, elicited information on a wide range of socio-demographic, lifestyle,
      and medical factors, including PSA screening. Usual frequency of consumption of
      63 food items two years prior to diagnosis/interview was collected, along with
      use of dietary supplements. Odds ratios (OR) and 95% confidence intervals (CI)
      between vitamin C intake and prostate cancer were estimated using logistic or
      polytomous regression, adjusting for potential confounders. Results: We observed
      no association between dietary intakes of vitamin C (OR for upper vs. lower
      tertile: 0.95, 95%CI 0.77, 1.18), estimated using the residual method to account
      for energy intake, or between regular use of vitamin C supplements and/or
      multivitamins (OR 0.90, 95%CI 0.76-1.05), and overall prostate cancer. Analyses
      considering disease aggressiveness, or restricted to subjects recently screened
      with PSA, thereby limiting the potential for undiagnosed cancers in non-cases,
      generated results consistent with those from the main analyses. Conclusion: Our
      findings document the absence of an association between recent dietary vitamin C
      intake, or supplementation, and prostate cancer incidence overall or prostate
      cancer grade at diagnosis. Based on this, and other available evidence, vitamin C
      intake does not seem to hold promises with regard to prostate cancer prevention.

PMID- 30233397
TI  - Cell Type-Dependent Activation Sequence During Rhythmic Bursting in the
      PreBotzinger Complex in Respiratory Rhythmic Slices From Mice.
AB  - Spontaneous respiratory rhythmic burst activity can be preserved in the
      preBotzinger Complex (preBotC) of rodent medullary transverse slices. It is
      known, that the activation sequence of inspiratory neurons in the preBotC
      stochastically varies from cycle to cycle. To test whether the activation timing
      of an inspiratory neuron depends on its neurotransmitter, we performed calcium
      imaging of preBotC neurons using double-transgenic mice expressing EGFP in GlyT2+
      neurons and tdTomato in GAD65+ neurons. Five types of inspiratory neurons were
      identified using the fluorescence protein expression and the maximum cross
      correlation coefficient between neuronal calcium fluctuation and field potential.
      Regarding the activation sequence, irregular type putative excitatory (GlyT2
      /GAD65-) neurons and irregular type glycinergic (GlyT2+/GAD65-) neurons tended to
      be activated early, while regular type putative excitatory neurons, regular type
      glycinergic neurons tended to be activated later. In conclusion, the different
      cell types define a general framework for the stochastically changing activation
      sequence of inspiratory neurons in the preBotC.

PMID- 30233398
TI  - Muscle Atrophy Due to Nerve Damage Is Accompanied by Elevated Myofibrillar
      Protein Synthesis Rates.
AB  - Muscle loss is a severe complication of many medical conditions such as cancer,
      cardiac failure, muscular dystrophies, and nerve damage. The contribution of
      myofibrillar protein synthesis (MPS) to the loss of muscle mass after nerve
      damage is not clear. Using deuterium oxide (D2O) labeling, we demonstrate that
      MPS is significantly increased in rat m.tibialis anterior (TA) compared to
      control (3.23 +/- 0.72 [damaged] to 2.09 +/- 0.26%*day-1 [control]) after 4 weeks
      of nerve constriction injury. This is the case despite substantial loss of mass
      of the TA (350 +/- 96 mg [damaged] to 946 +/- 361 mg [control]). We also show
      that expression of regulatory proteins involved with MPS (p70s6k1: 2.4 +/- 0.3 AU
      [damaged] to 1.8 +/- 0.2 AU [control]) and muscle protein breakdown (MPB) (MAFbx:
      5.3 +/- 1.2 AU [damaged] to 1.4 +/- 0.4 AU [control]) are increased in nerve
      damaged muscle. Furthermore, the expression of p70s6k1 correlates with MPS rates
      (r2 = 0.57). In conclusion, this study shows that severe muscle wasting following
      nerve damage is accompanied by increased as opposed to decreased MPS.

PMID- 30233400
TI  - Identification of Autophagy-Related Gene 7 and Autophagic Cell Death in the
      Planarian Dugesia japonica.
AB  - Planarians undergo continuous body size remodeling under starvation or during
      regeneration. This process likely involves autophagy and autophagic cell death,
      but this hypothesis is supported by few studies. To test this hypothesis, we
      cloned and characterized autophagy-related gene 7 (Atg7) from the planarian
      Dugesia japonica (DjAtg7). The full-length cDNA of DjAtg7 measures 2272 bp and
      includes a 2082-bp open reading frame encoding 693 amino acids with a molecular
      weight of 79.06 kDa. The deduced amino acid sequence of DjAtg7 contains a
      conserved ATP-binding site and a catalytic active site of an E1-like enzyme
      belonging to the ATG7 superfamily. DjAtg7 transcripts are mainly expressed in
      intestinal tissues of the intact animals. After amputation, DjAtg7 was highly
      expressed at the newly regenerated intestinal branch on days 3-7 of regeneration
      and in the old tissue of the distal intestinal branch on day 10 of regeneration.
      However, knockdown of DjAtg7 by RNAi did not affect planarian regeneration and
      did not block autophagosome formation, which indicates that autophagy is more
      complex than previously expected. Interestingly, TEM clearly confirmed that
      autophagy and autophagic cell death occurred in the old tissues of the newly
      regenerated planarians and clearly revealed that the dying cell released vesicles
      containing cellular cytoplasmic contents into the extracellular space. Therefore,
      the autophagy and autophagic cell death that occurred in the old tissue not only
      met the demand for body remodeling but also met the demand for energy supply
      during planarian regeneration. Collectively, our work contributes to the
      understanding of autophagy and autophagic cell death in planarian regeneration
      and body remodeling.

PMID- 30233401
TI  - Comparison of Calcium Balancing Strategies During Hypothermic Acclimation of
      Tilapia (Oreochromis mossambicus) and Goldfish (Carassius auratus).
AB  - The body temperatures of teleost species fluctuate following changes in the
      aquatic environment. As such, decreased water temperature lowers the rates of
      biochemical reactions and affects many physiological processes, including active
      transport-dependent ion absorption. Previous studies have focused on the impacts
      of low temperature on the plasma ion concentrations or membrane transporters in
      fishes. However, very few in vivo or organism-level studies have been performed
      to more thoroughly elucidate the process of acclimation to low temperatures. In
      the present study, we compared the strategies for cold acclimation between
      stenothermic tilapia and eurythermic goldfish. Whole-body calcium content was
      more prominently diminished in tilapia than in goldfish after long-term cold
      exposure. This difference can be attributed to alterations in the transportation
      parameters for Ca2+ influx, i.e., maximum velocity (Vmax ) and binding affinity
      (1/Km ). There was also a significant difference in the regulation of Ca2+ efflux
      between the two fishes. Transcript levels for Ca2+ related transporters,
      including the Na+/Ca2+ exchanger and epithelial Ca2+ channel, were similarly
      regulated in both fishes. However, upregulation of plasma membrane Ca2+ATPase
      expression was more pronounced in goldfish than in tilapia. In addition, enhanced
      Na+/K+-ATPase abundance, which provides the major driving force for ion
      absorption, was only detected in tilapia, while upregulated Na+/K+-ATPase
      activity was only detected in goldfish. Based on the results of the present
      study, we have found that goldfish and tilapia differentially regulate gill
      epithelial plasma membrane Ca2+-ATPase (PMCA) expression and Na+/K+-ATPase
      activity in response to cold environments. These regulatory differences are
      potentially linked to more effective regulation of Ca2+ influx kinetics and
      better maintenance of whole body calcium content in goldfish than in tilapia.

PMID- 30233402
TI  - Effect of Black Tea Extract and Thearubigins on Osteoporosis in Rats and
      Osteoclast Formation in vitro.
AB  - Background: Osteoporosis is a major health problem that is closely related to
      substantial morbidity, mortality and decline in life quality for the aging
      population. Although previous studies and epidemiological evidence have
      demonstrated an association between black tea consumption and the prevention of
      bone loss, the underlying mechanism remains unclear. So, the effect of black tea
      extract (BTE) and thearubigins (TRs) on osteoporosis in rats and osteoclast
      formation in vitro were investigated. Methods:In vivo, ovariectomized (OVX) rats
      were used to establish osteoporosis models. To validate the model and study the
      effects of BTE and TRs on osteoporosis, the female Wistar rats were divided into
      a sham-operated group and five OVX groups including model, Xian-Ling-Gu-Bao
      (XLGB) (as a positive control), BTE, TRs low-dose, and TRs high-dose group. The
      rats in the four treatment groups were given the corresponding test sample for 12
      weeks. Then, the body weight, femur indices, and serum biomarkers were examined
      and analyzed. In vitro, RAW264.7 murine macrophages were used as model of
      osteoclast formation. The effects of BTE and TRs on osteoclasts formation and the
      specific genes and protein levels of osteoclasts were determined. Results:
      Although there was no significant effect on the OVX-induced body weight gain by
      BTE or TRs, the levels of maximum bending force, cortical bone thickness and
      biomarker of bone resorption (acid phosphatase) can be significantly ameliorated
      by BTE or TRs in OVX rats. Furthermore, both of BTE and TRs can inhibit the
      osteoclastogenesis and diminish the expression levels of the related genes and
      proteins.

PMID- 30233403
TI  - Predictive Value of T peak - T end Indices for Adverse Outcomes in Acquired QT
      Prolongation: A Meta-Analysis.
AB  - Background: Acquired QT interval prolongation has been linked with malignant
      ventricular arrhythmias, such as torsade de pointes, in turn predisposing to
      sudden cardiac death. Increased dispersion of repolarization has been identified
      as a pro-arrhythmic factor and can be observed as longer Tpeak - Tend interval
      and higher Tpeak - Tend/QT ratio on the electrocardiogram. However, the values of
      these repolarization indices for predicting adverse outcomes in this context have
      not been systematically evaluated. Method: PubMed, Embase and Cochrane Library
      databases were searched until 14th February 2018, identifying 232 studies.
      Results: Five studies on acquired QT prolongation met the inclusion criteria and
      308 subjects with drug-induced LQTS patients (mean age: 66 +/- 18 years old; 46%
      male) were included in this meta-analysis. Tpeak - Tend intervals were longer
      [mean difference [MD]: 76 ms, standard error [SE]: 26 ms, P = 0.003; I2 = 98%]
      and Tpeak - Tend/QT ratios were higher (MD: 0.14, SE: 0.03, P = 0.000; I2 = 29%)
      in patients with torsade de pointes compared to those without these events.
      Conclusion: Tpeak - Tend interval and Tpeak - Tend/QT ratio were higher in
      patients with acquired QT prolongation suffering from torsade de pointes compared
      to those who did not. These repolarization indices may provide additional
      predictive value for identifying high-risk individuals.

PMID- 30233399
TI  - Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial
      Fibrillation: Recent Advances and Future Challenges.
AB  - The pathophysiology of atrial fibrillation (AF) is broad, with components related
      to the unique and diverse cellular electrophysiology of atrial myocytes,
      structural complexity, and heterogeneity of atrial tissue, and pronounced disease
      associated remodeling of both cells and tissue. A major challenge for rational
      design of AF therapy, particularly pharmacotherapy, is integrating these
      multiscale characteristics to identify approaches that are both efficacious and
      independent of ventricular contraindications. Computational modeling has long
      been touted as a basis for achieving such integration in a rapid, economical, and
      scalable manner. However, computational pipelines for AF-specific drug screening
      are in their infancy, and while the field is progressing quite rapidly, major
      challenges remain before computational approaches can fill the role of workhorse
      in rational design of AF pharmacotherapies. In this review, we briefly detail the
      unique aspects of AF pathophysiology that determine requirements for compounds
      targeting AF rhythm control, with emphasis on delimiting mechanisms that promote
      AF triggers from those providing substrate or supporting reentry. We then
      describe modeling approaches that have been used to assess the outcomes of drugs
      acting on established AF targets, as well as on novel promising targets including
      the ultra-rapidly activating delayed rectifier potassium current, the
      acetylcholine-activated potassium current and the small conductance calcium
      activated potassium channel. Finally, we describe how heterogeneity and
      variability are being incorporated into AF-specific models, and how these
      approaches are yielding novel insights into the basic physiology of disease, as
      well as aiding identification of the important molecular players in the complex
      AF etiology.

PMID- 30233405
TI  - N6-(2-Hydroxyethyl) Adenosine From Cordyceps cicadae Ameliorates Renal
      Interstitial Fibrosis and Prevents Inflammation via TGF-beta1/Smad and NF-kappaB
      Signaling Pathway.
AB  - Renal interstitial fibrosis is characterized by inflammation and an excessive
      accumulation of extracellular matrix, which leads to end-stage renal failure. Our
      previous studies have shown that a natural product from Cordyceps cicadae can
      ameliorate chronic kidney diseases. N6-(2-Hydroxyethyl) adenosine (HEA), a
      physiologically active compound in C. cicadae, has been identified as a Ca2+
      antagonist and an anti-inflammatory agent in pharmacological tests. However, its
      role in renal interstitial fibrosis and the underlying mechanism remains unclear.
      Here, unilateral ureteral obstruction (UUO) was used to induce renal interstitial
      fibrosis in male C57BL/6 mice. Different doses of HEA (2.5, 5, and 7.5 mg/kg)
      were given by intraperitoneal injection 24 h before UUO, and the treatment was
      continued for 14 days post-operatively. Histologic changes were examined by
      hematoxylin & eosin, Masson's trichrome, and picrosirius red stain. Quantitative
      real-time PCR analysis, enzyme-linked immunosorbent assays, immunohistochemistry,
      and western blot analysis were used to evaluate proteins levels. And the results
      showed that HEA significantly decreased UUO-induced renal tubular injury and
      fibrosis. In vivo, HEA apparently decreased UUO-induced inflammation and renal
      fibroblast activation by suppression of the NF-kappaB and TGF-beta1/Smad
      signaling pathway. In vitro, HEA also obviously decreased lipopolysaccharide
      induced inflammatory cytokine level in RAW 264.7 cells and TGF-beta1-induced
      fibroblast activation in NRK-49F cells by modulating NF-kappaB and TGF-beta1/Smad
      signaling. In general, our findings indicate that HEA has a beneficial effect on
      UUO-induced tubulointerstitial fibrosis by suppression of inflammatory and renal
      fibroblast activation, which may be a potential therapy in chronic conditions
      such as renal interstitial fibrosis.

PMID- 30233406
TI  - Key Role of the Membrane Trafficking of Nav1.5 Channel Protein in Antidepressant
      Induced Brugada Syndrome.
AB  - Anti-depressant treatment has been found to be associated with the development of
      Brugada syndrome (BrS) through poorly defined mechanisms. Herein, this study
      aimed to explore the molecular basis for amitriptyline-induced BrS. The effects
      of long-term treatments of amitriptyline on Nav1.5 were investigated using
      neonatal rat ventricular myocytes. The electrophysiological properties,
      expression and distribution of Nav1.5 were studied using the patch clamp, Western
      blot and confocal laser microscopy assays. Interactions between Nav1.5 and its
      interacting proteins, including ankyrin-G and dystrophin, were evaluated by co
      immunoprecipitation. A larger decrease in the peak INa occurred after long-term
      treatments to amitriptyline (56.64%) than after acute exposure to amitriptyline
      (28%). Slow recovery from inactivation of Nav1.5 was observed after acute or long
      term treatments to amitriptyline. The expression of Nav1.5 on the cell membrane
      showed a larger decrease by long-term treatments to amitriptyline than by acute
      exposure to amitriptyline. After long-term treatments to amitriptyline, we
      observed reduced Nav1.5 proteins on the cell membrane and the disrupted co
      localization of Nav1.5 and ankyrin-G or dystrophin. Co-immunoprecipitation
      experiments further testified that the combination of Nav1.5 and ankyrin-G or
      dystrophin was severely weakened after long-term treatments to amitriptyline,
      implying the failed interaction between Nav1.5 and ankyrin-G or dystrophin. Our
      data suggest that the long-term effect of amitriptyline serves as an important
      contribution to BrS induced by amitriptyline. The mechanisms of BrS induced by
      amitriptyline were related to Nav1.5 trafficking and could be explained by the
      disrupted interaction of ankyrin-G, dystrophin and Nav1.5.

PMID- 30233404
TI  - Cardiac Arrhythmias as Manifestations of Nanopathies: An Emerging View.
AB  - A nanodomain is a collection of proteins localized within a specialized,
      nanoscale structural environment, which can serve as the functional unit of
      macroscopic physiologic processes. We are beginning to recognize the key roles of
      cardiomyocyte nanodomains in essential processes of cardiac physiology such as
      electrical impulse propagation and excitation-contraction coupling (ECC). There
      is growing appreciation of nanodomain dysfunction, i.e., nanopathy, as a
      mechanistic driver of life-threatening arrhythmias in a variety of pathologies.
      Here, we offer an overview of current research on the role of nanodomains in
      cardiac physiology with particular emphasis on: (1) sodium channel-rich
      nanodomains within the intercalated disk that participate in cell-to-cell
      electrical coupling and (2) dyadic nanodomains located along transverse tubules
      that participate in ECC. The beat to beat function of cardiomyocytes involves
      three phases: the action potential, the calcium transient, and mechanical
      contraction/relaxation. In all these phases, cell-wide function results from the
      aggregation of the stochastic function of individual proteins. While it has long
      been known that proteins that exist in close proximity influence each other's
      function, it is increasingly appreciated that there exist nanoscale structures
      that act as functional units of cardiac biophysical phenomena. Termed
      nanodomains, these structures are collections of proteins, localized within
      specialized nanoscale structural environments. The nano-environments enable the
      generation of localized electrical and/or chemical gradients, thereby conferring
      unique functional properties to these units. Thus, the function of a nanodomain
      is determined by its protein constituents as well as their local structural
      environment, adding an additional layer of complexity to cardiac biology and
      biophysics. However, with the emergence of experimental techniques that allow
      direct investigation of structure and function at the nanoscale, our
      understanding of cardiac physiology and pathophysiology at these scales is
      rapidly advancing. Here, we will discuss the structure and functions of multiple
      cardiomyocyte nanodomains, and novel strategies that target them for the
      treatment of cardiac arrhythmias.

PMID- 30233407
TI  - An Insect Prostaglandin E2 Synthase Acts in Immunity and Reproduction.
AB  - Eicosanoids, oxygenated metabolites of C20 polyunsaturated fatty acids (PUFAs),
      mediate fundamental physiological processes, including immune reactions and
      reproduction, in insects. Prostaglandins (PGs) make up one group of eicosanoids,
      of which PGE2 is a relatively well-known mediator in various insect taxa. While
      PG biosynthesis has been reported, the specific biosynthetic pathway for PGE2 is
      not known in insects. Here, we posed the hypothesis that Se-mPGES2 mediates
      biosynthesis of physiologically active PGE2 through its cognate protein. To test
      this hypothesis, we interrogated a transcriptome of the lepidopteran insect,
      Spodoptera exigua, to identify a candidate PGE2 synthase (Se-mPGES2) and analyzed
      its sequence and expression. Its predicted amino acid sequence contains a
      consensus thioredoxin homology sequence (Cys-x-x-Cys) responsible for catalytic
      activity along with an N-terminal membrane-associated hydrophobic domain and C
      terminal cytosolic domain. It also shares sequence homology (36.5%) and shares
      almost overlapping three dimensional structures with a membrane-bound human PGES2
      (mPGES2). Se-mPGES2 was expressed in all developmental stages with high peaks
      during the late larval instar and adult stages. Immune challenge significantly up
      regulated its expression levels in hemocytes and fat body. Injecting double
      stranded RNA (dsRNA) specific to Se-mPGES2 significantly impaired two cellular
      immune responses, hemocyte-spreading behavior and nodule formation following
      bacterial challenge. Humoral immunity was also significantly suppressed,
      registered as reduced phenoloxidase activity and antimicrobial peptide expression
      levels. The suppressed immune responses were reversed following PGE2, but not
      arachidonic acid (AA), treatments. RNAi treatments also reduced the egg-laying
      behavior of females. Control females mated with the RNAi-treated males led to
      substantially reduced egg-laying behavior, which was also reversed following PGE2
      injections into females. These results strongly bolster our hypothesis that Se
      mPGES2 acts in the biosynthesis of PGE2, a crucial biochemical signal mediating
      immune and reproductive physiology of S. exigua.

PMID- 30233408
TI  - Investigating the Fractal Dimension of the Foveal Microvasculature in Relation to
      the Morphology of the Foveal Avascular Zone and to the Macular Circulation in
      Patients With Type 2 Diabetes Mellitus.
AB  - In this study, we examined the relationship between the fractal dimension (FD),
      the morphology of the foveal avascular zone (FAZ) and the macular circulation in
      healthy controls and patients with type 2 diabetes mellitus (T2DM) with and with
      no diabetic retinopathy (DR). Cross-sectional data of 47 subjects were analyzed
      from a 5-year longitudinal study using a multimodal optical imaging approach.
      Healthy eyes from nondiabetic volunteers (n = 12) were selected as controls. Eyes
      from patients with T2DM were selected and divided into two groups: diabetic
      subjects with mild DR (MDR group, n = 15) and subjects with DM but without DR (DM
      group, n = 20). Our results demonstrated a higher FD in the healthy group (mean,
      1.42 +/- 0.03) than in the DM and MDR groups (1.39 +/- 0.02 and 1.35 +/- 0.03,
      respectively). Also, a bigger perimeter, area, and roundness of the FAZ were
      found in MDR eyes. A significant difference in area and perimeter (p <= 0.005)
      was observed for the MDR group supporting the enlargement of the FAZ due to
      diabetic complications in the eye. A moderate positive correlation (p = 0.014, R2
      = 43.8%) between the FD and blood flow rate (BFR) was only found in the healthy
      control group. The BFR calculations revealed the lowest values in the MDR group
      (0.98 +/- 0.27 MUl/s vs. 1.36 +/- 0.86 MUl/s and 1.36 +/- 0.57 MUl/sec in the
      MDR, DM, and healthy groups, respectively, p = 0.2). Our study suggests that the
      FD of the foveal vessel arborization could provide useful information to identify
      early morphological changes in the retina of patients with T2DM. Our results also
      indicate that the enlargement and asymmetry of the FAZ might be related to a
      lower BFR because of the DR onset and progression. Interestingly, due to the lack
      of FAZ symmetry observed in the DM and MDR eyes, it appears that the distribution
      of flow within the retinal vessels loses complexity as the vascular structures
      distributing the flow are not well described by fractal branching. Further
      research could determine how our approach may be used to aid the diagnosis of
      retinal neurodegeneration and vascular impairment at the early stage of DR.

PMID- 30233409
TI  - RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a
      Galphai2-Protein/PI3Kbeta/gamma/Nitric Oxide-Coupled Pathway.
AB  - Background: Relaxins are small peptide hormones, which are novel candidate
      molecules that play important roles in cardiometablic syndrome. Relaxins are
      structurally related to the insulin hormone superfamily, which provide
      vasodilatory effects by activation of G-protein-coupled relaxin receptors (RXFPs)
      and stimulation of endogenous nitric oxide (NO) generation. Recently, relaxin
      could be demonstrated to activate Gi proteins and phosphoinositide 3-kinase
      (PI3K) pathways in cultured endothelial cells in vitro. However, the contribution
      of the Gi-PI3K pathway and their individual components in relaxin-dependent
      relaxation of intact arteries remains elusive. Methods: We used Galphai2- (Gnai2
      /-) and Galphai3-deficient (Gnai3-/-) mice, pharmacological tools and wire
      myography to study G-protein-coupled signaling pathways involved in relaxation of
      mouse isolated mesenteric arteries by relaxins. Human relaxin-1, relaxin-2, and
      relaxin-3 were tested. Results: Relaxin-2 (~50% relaxation at 10-11 M) was the
      most potent vasodilatory relaxin in mouse mesenteric arteries, compared to
      relaxin-1 and relaxin-3. The vasodilatory effects of relaxin-2 were inhibited by
      removal of the endothelium or treatment of the vessels with N (G)-nitro-L
      arginine methyl ester (L-NAME, endothelial nitric oxide synthase (eNOS)
      inhibitor) or simazine (RXFP1 inhibitor). The vasodilatory effects of relaxin-2
      were absent in arteries of mice treated with pertussis toxin (PTX). They were
      also absent in arteries isolated from Gnai2-/- mice, but not from Gnai3-/- mice.
      The effects were not affected by FR900359 (Galphaq protein inhibitor) or PI-103
      (PI3Kalpha inhibitor), but inhibited by TGX-221 (PI3Kbeta inhibitor) or AS-252424
      (PI3Kgamma inhibitor). Simazine did not influence the anti-contractile effect of
      perivascular adipose tissue. Conclusion: Our data indicate that relaxin-2
      produces endothelium- and NO-dependent relaxation of mouse mesenteric arteries by
      activation of RXFP1 coupled to Gi2-PI3K-eNOS pathway. Targeting vasodilatory Gi
      protein-coupled RXFP1 pathways may provide promising opportunities for drug
      discovery in endothelial dysfunction and cardiometabolic disease.

PMID- 30233410
TI  - History of Preeclampsia Adds to the Deleterious Effect of Chronic Stress on the
      Cardiac Ability to Flexibly Adapt to Challenge.
AB  - Preeclampsia, a pregnancy-specific disorder, presents a major health problem
      during gestation, but is also associated with increased risk for cardiovascular
      complications in later life. We aimed to investigate whether chronic stress
      experience and preeclampsia may have additive adverse effects on the cardiac
      ability to flexibly adapt to challenge, that is, to mount an appropriately
      vigorous heart rate response to an acute psychological challenge, or whether they
      may perhaps have synergistic effects (e.g., mutual augmentation of effects).
      Blunted cardiac responding to challenge has been linked to poor health outcomes
      in the longer term. Women previously affected by preeclampsia and women after
      uncomplicated pregnancies were tested 15-17 weeks post-partum in a standardized
      stress-reactivity protocol, while cardiovascular variables were simultaneously
      recorded. Changes in heart rate and blood pressure in response to the stressor
      were analyzed with regard to the effects of history of preeclampsia and chronic
      stress experience. Findings indicated blunted cardiac responses in women with
      higher chronic stress experience (p = 0.020) and, independently from that, in
      women with a history of preeclampsia (p = 0.018), pointing to an additive nature
      of the effects of preeclampsia and chronic stress on impaired cardiovascular
      functioning. Consequently, if both are present, a history of preeclampsia may add
      to the already deleterious effects of the experience of chronic stress. The
      additive nature of the effects suggests that stress-reducing interventions,
      albeit they will not eliminate the heightened cardiovascular risk in patients
      with a history of preeclampsia, may improve their overall prognosis by avoiding
      further accumulation of risk.

PMID- 30233411
TI  - Preserved Adrenal Function After Lumbar Spinal Cord Transection Augments Low
      Pressure Bladder Activity in the Rat.
AB  - Spinal cord injury (SCI) disconnects supraspinal micturition centers from the
      lower urinary tract resulting in immediate and long-term changes in bladder
      structure and function. While cervical and high thoracic SCI have a greater range
      of systemic effects, clinical data suggest that those with lower (suprasacral)
      injuries develop poorer bladder outcomes. Here we assess the impact of SCI level
      on acute changes in bladder activity. We used two SCI models, T3 and L2 complete
      transections in male Wistar rats, and compared bladder pressure fluctuations to
      those of naive and bladder-denervated animals. By 2 days after L2 transection,
      but not T3 transection or bladder denervation, small amplitude rhythmic
      contractions (1 mmHg, 0.06 Hz) were present at low intravesical pressures (<6
      mmHg); these were still present 1 month following injury, and at 3 months,
      bladders from L2 SCI animals were significantly larger than those from T3 SCI or
      naive animals. Low-pressure contractions were unaffected by blocking ganglionic
      signaling or bladder denervation at the time of measurements. L2 (and sham
      surgery) but not T3 transection preserves supraspinal adrenal control, and by
      ELISA we show lower plasma adrenal catecholamine concentration in the latter.
      When an adrenalectomy preceded the L2 transection, the aberrant low-pressure
      contractions more closely resembled those after T3 transection, indicating that
      the increased bladder activity after lumbar SCI is mediated by preserved adrenal
      function. Since ongoing low-pressure contractions may condition the detrusor and
      exacerbate detrusor-sphincter dyssynergia, moderating bladder catecholamine
      signaling may be a clinically viable intervention strategy.

PMID- 30233412
TI  - Limb Skin Temperature as a Tool to Predict Orthostatic Instability.
AB  - Orthostatic instability is one of the main consequences of weightlessness or
      gravity challenge and plays as well a crucial role in public health, being one of
      the most frequent disease of aging. Therefore, the assessment of effective
      countermeasures, or even the possibility to predict, and thus prevent orthostatic
      instability is of great importance. Heat stress affects orthostatic stability and
      may lead to impaired consciousness and decrease in cerebral perfusion,
      specifically during the exposure to G-forces. Conversely, peripheral cooling can
      prevent orthostatic intolerance - even in normothermic healthy subjects.
      Indicators of peripheral vasodilation, as elevated skin surface temperatures, may
      mirror blood decentralization and an increased risk of orthostatic instability.
      Therefore, the aim of this study was to quantify orthostatic instability risk, by
      assessing in 20 fighter jet pilot candidates' cutaneous limb temperatures, with
      respect to the occurrence of G-force-induced almost loss of consciousness (ALOC),
      before and during exposure to a push-pull maneuver, i.e., head-down tilt,
      combined with lower body negative pressure. Peripheral skin temperatures from the
      upper and lower (both proximal and distal) extremities and core body temperature
      via heat-flux approach (i.e., the Double Sensor), were continuously measured
      before and during the maneuver. The 55% of subjects that suffered an ALOC during
      the procedure had higher upper arm and thigh temperatures at baseline compared to
      the 45% that remained stable. No difference in baseline core body temperature and
      distal limbs (both upper and lower) skin temperatures were found between the two
      groups. Therefore, peripheral skin temperature data could be considered a
      predicting factor for ALOC, prior to rapid onset acceleration. Moreover, these
      findings could also find applications in patient care settings such as in
      intensive care units.

PMID- 30233413
TI  - Estrogen Therapy Worsens Cardiac Function and Remodeling and Reverses the Effects
      of Exercise Training After Myocardial Infarction in Ovariectomized Female Rats.
AB  - There is an increase in the incidence of cardiovascular events such as myocardial
      infarction (MI) after menopause. However, the use of estrogen therapy (E2)
      remains controversial. The aim of this study was to evaluate the effects of E2,
      alone and combined with exercise training (ET), on cardiac function and
      remodeling in ovariectomized (OVX) rats after MI. Wistar female rats underwent
      ovariectomy, followed by MI induction were separated into five groups: S; MI;
      MI+ET; MI+E2; and MI+ET+E2. Fifteen days after MI or sham surgery, treadmill ET
      and/or estrogen therapy [17-beta estradiol-3-benzoate (E2), s.c. three
      times/week] were initiated and maintained for 8 weeks. After the treatment and/or
      training period, the animals underwent cardiac hemodynamic evaluation through
      catheterization of the left ventricle (LV); the LV systolic and diastolic
      pressures (LVSP and LVEDP, respectively), maximum LV contraction and relaxation
      derivatives (dP/dt+ and dP/dt-), and isovolumic relaxation time (Tau) were
      assessed. Moreover, histological analyses of the heart (collagen and
      hypertrophy), cardiac oxidative stress [advanced oxidation protein products
      (AOPPs)], pro- and antioxidant protein expression by Western blotting and
      antioxidant enzyme activity in the heart were evaluated. The MI reduced the LVSP,
      dP/dt+ and dP/dt- but increased the LVEDP and Tau. E2 did not prevent the MI
      induced changes in cardiac function, even when combined with ET. An increase in
      the dP/dt+ was observed in the E2 group compared with the MI group. There were no
      changes in collagen deposition and myocyte hypertrophy caused by the treatments.
      The increases in AOPP, gp91-phox, and angiotensin II type 1 receptor expression
      induced by MI were not reduced by E2. There were no changes in the expression of
      catalase caused by MI or by the treatments, although, a reduction in superoxide
      dismutase (SOD) expression occurred in the groups subjected to E2 treatment.
      Whereas there were post-MI reductions in activities of SOD and catalase enzymes,
      only that of SOD was prevented by ET. Therefore, we conclude that E2 therapy does
      not prevent the MI-induced changes in cardiac function and worsens parameters
      related to cardiac remodeling. Moreover, E2 reverses the positive effects of ET
      when used in combination, in OVX infarcted female rats.

PMID- 30233415
TI  - Impact of Lactobacillus casei BL23 on the Host Transcriptome, Growth and Disease
      Resistance in Larval Zebrafish.
AB  - In this study, zebrafish were treated with Lactobacillus strains as probiotics
      from hatching to puberty, and the effect of treatment with L. casei BL23 on the
      development and immunity response of the host was investigated. Genes that were
      differentially expressed (DEGs) in the overall body and intestine were detected
      at 14 days post fertilization (dpf) and 35 dpf, respectively, using whole
      transcriptome sequencing (mRNAseq). We showed that zebrafish raised by continuous
      immersion with L. casei BL23 showed a higher final body weight at 14 dpf (P <
      0.05), and 35 dpf (P < 0.01). DEGs between L. casei BL23 treatment and control
      group at 14 dpf were involved in myogenesis, cell adhesion, transcription
      regulation and DNA-binding and activator. At 35 dpf, 369 genes were DEGs in the
      intestine after treatment with L. casei BL23, which were involved in such
      categories as signaling, secretion, motor proteins, oxidoreductase and iron,
      tight junctions, lipid metabolism, growth regulation, proteases, and humoral and
      cellular effectors. KEGG analysis showed DEGs to be involved in such pathways as
      those associated with tight junctions and the PPAR signal pathway. RT-qPCR
      analysis showed that expression of insulin-like growth factors-I (igf1),
      peroxisome proliferator activated receptors-alpha (ppar-alpha) and -beta (ppar
      beta), Vitamin D receptor-alpha (vdr-alpha), and retinoic acid receptor-gamma
      (rar-gamma) was up-regulated in fish treated with L. casei BL23 at 35 dpf. After
      35 days of treatment, the mortality rate in L. casei BL23 treated group was lower
      than the control after challenge with A. hydrophila (P < 0.05), and the pro
      inflammatory cytokine il-1beta, anti-inflammatory cytokine il-10 and complement
      component 3a (c3a) showed more expression in L. casei BL23 group at 8h after
      challenge, 24 h after challenge, or both.. Together, these data suggest that
      specific Lactobacillus probiotic strains can accelerate the development profile
      and enhance immunity in zebrafish, which supports the rationale of early
      administration of probiotics in aquaculture.

PMID- 30233416
TI  - L-Threonine Supplementation During Colitis Onset Delays Disease Recovery.
AB  - Dietary nutrients have emerged as potential therapeutic adjuncts for inflammatory
      bowel disease (IBD) given their impact on intestinal homeostasis through the
      modulation of immune response, gut microbiota composition and epithelial barrier
      stability. Several nutrients have already been associated with a protective
      phenotype. Yet, there is a lack of knowledge toward the most promising ones as
      well as the most adequate phase of action. To unveil the most prominent therapy
      candidates we characterized the colon metabolic profile during colitis
      development. We have observed a twofold decrease in threonine levels in mice
      subjected to DSS-induced colitis. We then assessed the effect of threonine
      supplementation in the beginning of the inflammatory process (DSS + Thr) or when
      inflammation is already established (DSS + Thr D8). Colitis progression was
      similar between the treated groups and control colitic mice, yet threonine had a
      surprisingly detrimental effect when administered in the beginning of the
      disease, with mice displaying a delayed recovery when compared to control mice
      and mice supplemented with threonine after day 8. Although no major changes were
      found in their metabolic profile, DSS + Thr mice displayed altered expression in
      mucin-encoding genes, as well as in goblet cell counts, unveiling an impaired
      ability to produce mucus. Moreover, IL-22 secretion was decreased in DSS + Thr
      mice when compared to DSS + Thr D8 mice. Overall, these results suggest that
      supplementation with threonine during colitis induction impact goblet cell number
      and delays the recovery period. This reinforces the importance of a deeper
      understanding regarding threonine supplementation in IBD.

PMID- 30233414
TI  - The Peripheral Stalk of Rotary ATPases.
AB  - Rotary ATPases are a family of enzymes that are thought of as molecular
      nanomotors and are classified in three types: F, A, and V-type ATPases. Two
      members (F and A-type) can synthesize and hydrolyze ATP, depending on the
      energetic needs of the cell, while the V-type enzyme exhibits only a hydrolytic
      activity. The overall architecture of all these enzymes is conserved and three
      main sectors are distinguished: a catalytic core, a rotor and a stator or
      peripheral stalk. The peripheral stalks of the A and V-types are highly conserved
      in both structure and function, however, the F-type peripheral stalks have
      divergent structures. Furthermore, the peripheral stalk has other roles beyond
      its stator function, as evidenced by several biochemical and recent structural
      studies. This review describes the information regarding the organization of the
      peripheral stalk components of F, A, and V-ATPases, highlighting the key
      differences between the studied enzymes, as well as the different processes in
      which the structure is involved.

PMID- 30233417
TI  - Intermediate Muscle Length and Tendon Vibration Optimize Corticospinal
      Excitability During Knee Extensors Local Vibration.
AB  - While local vibration (LV) has been recently proposed as a potential modality for
      neuromuscular conditioning, no practical recommendations to optimize its effects
      have been published. Because changes in corticospinal excitability may reflect at
      which degree the neuromuscular function is modulated during LV exposure, this
      study investigated the effects of muscle length and vibration site on LV-induced
      on motor evoked potentials (MEPs) changes. Twenty-one subjects participated in a
      single session in which MEPs were evoked on the relaxed knee extensors (KE)
      during three conditions, i.e., no vibration (CON), muscle (VIBMU), and tendon
      vibration (VIBTD). Three muscle lengths were tested for each condition, i.e.,
      short/intermediate/long KE muscle length. Both VIBMU and VIBTD significantly
      increase MEPs compared to CON. Higher increases (P < 0.001) were found for VIBTD
      compared to VIBMU for vastus lateralis (mean increases of the three angles: +241%
      vs.+ 148%), vastus medialis (+273% vs. + 180%) and rectus femoris muscles (+191%
      vs. +141%). The increase in MEPs amplitude was higher (p < 0.001) at an
      intermediate (mean pooled increase for VIBTD and VIBMU: +265%, +290%, and +212%
      for VL, VM, and RF, respectively) compared to short (+136%, + 144%, and + 127%)
      or long (+ 184%, + 246% and + 160%) muscle lengths. These results suggest that LV
      should be applied to the tendon at an intermediate muscle length to optimize the
      acute effects of LV on the KE neuromuscular function.

PMID- 30233419
TI  - Stressful Life Memories Relate to Ruminative Thoughts in Women With Sexual
      Violence History, Irrespective of PTSD.
AB  - More than one in every four women in the world experience sexual violence (SV) in
      their lifetime, most often as teenagers and young adults. These traumatic
      experiences leave memories in the brain, which are difficult if not impossible to
      forget. We asked whether women with SV history experience stronger memories of
      their most stressful life event than women without SV history and if so, whether
      strength relates to ruminative and trauma-related thoughts. Using the
      Autobiographical Memory Questionnaire (AMQ), women with SV history (n = 64)
      reported this memory as especially strong (p < 0.001), remembering more sensory
      and contextual details, compared to women without SV history (n = 119). They
      further considered the event a significant part of their personal life story. The
      strength of the memory was highly correlated with posttraumatic cognitions and
      ruminative thoughts, as well as symptoms of depression and anxiety (p's < 0.001,
      n = 183). A third (33%) of the women with SV history were diagnosed with
      posttraumatic stress disorder (PTSD), but PTSD alone did not account for the
      increase in memory strength (p's < 0.001). These data suggest that the experience
      of SV increases the strength of stressful autobiographical memories, which are
      then reexperienced in everyday life during posttraumatic and ruminative thoughts.
      We propose that the repeated rehearsal of vivid stressful life memories generates
      more trauma memories in the brain, making the experience of SV even more
      difficult to forget.

PMID- 30233420
TI  - Increased Absolute Glutamate Concentrations and Glutamate-to-Creatine Ratios in
      Patients With Methamphetamine Use Disorders.
AB  - Introduction: Previous studies have indicated that changes in the concentration
      of glutamate and related metabolites may mediate the progression of addiction in
      patients with methamphetamine (MA) use disorders. In the present study, we
      utilized magnetic resonance spectroscopy (MRS) to investigate absolute glutamate
      concentrations and metabolite ratios in patients with MA addiction. We further
      analyzed the association between glutamate concentration and various clinical
      indicators. Methods: The present study included 31 unmedicated patients with
      clinically diagnosed MA dependence (mean age: 30.5 +/- 8.0 years) and 32 age
      matched healthy controls (mean age: 32.9 +/- 8.2 years). Patients were evaluated
      using the Barratt Impulsiveness Scale (BIS-11). We also collected general
      information regarding the duration and dosage of drug use. Point-resolved
      spectroscopy was used to quantify the absolute concentrations of metabolites
      (glutamate, choline, N-acetylaspartate, glutamine, and creatine), as well as the
      ratio of metabolites to total creatine, using LCModel software. We then compared
      differences in glutamate levels and psychometric scores between the two groups.
      Results: Glutamate-to-creatine ratios in the brainstem were significantly higher
      in the MA group than in the control group (t = 2.764, p = 0.008). Glutamate
      concentrations in the brainstem were also significantly higher in the MA group
      than in the control group (t = 2.390, p = 0.020). However, no significant
      differences in the concentrations or ratios of other metabolites were observed
      between the two groups (all p > 0.05). Glutamate concentration was positively
      correlated with the duration of drug use (r = 0.401, p = 0.035) and the total
      dose of regular addiction (duration of addiction * regular addiction dose; r =
      0.207, p = .040), but not with BIS-11 scores. Conclusions: Our findings indicated
      that glutamate levels in the brainstem are significantly elevated in patients
      with MA use disorders, and that these levels are significantly associated with
      the duration and dose of drug use.Such findings suggest that glutamate
      concentration can be used as an objective biological marker for
      evaluating/monitoring disease status and treatment efficacy in patients with MA
      dependence.

PMID- 30233421
TI  - Subregions of the Anterior Cingulate Cortex Form Distinct Functional Connectivity
      Patterns in Young Males With Internet Gaming Disorder With Comorbid Depression.
AB  - Depression is one of the most common comorbid conditions in Internet Gaming
      Disorder (IGD). Although there have been many studies on the pathophysiology of
      IGD, the neurobiological basis underlying the close association between
      depression and IGD has not been fully clarified. Previous neuroimaging studies
      have demonstrated functional and structural abnormalities in the anterior
      cingulate cortex (ACC) in IGD patients. In this study, we explored functional
      connectivity (FC) abnormalities involving subregions of the ACC in IGD subjects
      with comorbid depression. We performed a resting state seed-based FC analysis of
      21 male young adults with IGD with comorbid depression (IGDdep+ group, 23.6 +/-
      2.4 years), 22 male young adults without IGD with comorbid depression (IGDdep-
      group, 24.0 +/- 1.6 years), and 20 male age-matched healthy controls (24.0 +/-
      2.2 years). ACC-seeded FC was evaluated using the CONN-fMRI FC toolbox. The
      dorsal ACC (dACC), the pregenual ACC (pgACC), and the subgenual ACC (sgACC) were
      selected as seed regions. Both IGD groups had stronger pgACC FC with the right
      precuneus, the posterior cingulate cortex, and the left inferior frontal
      gyrus/insula than the control group. The IGDdep+ group had stronger dACC FC with
      the left precuneus and the right cerebellar lobule IX than the control and IGDdep
      groups. The IGDdep+ group also had weaker pgACC FC with the right dorsomedial
      prefrontal cortex and the right supplementary motor area and had weaker sgACC FC
      with the left precuneus, the left lingual gyrus, and the left postcentral gyrus
      than the other groups. The strength of the connectivity between the sgACC and the
      left precuneus correlated positively with a higher omission error rate in the
      continuous performance test in the IGDdep+ group. In addition, the IGDdep- group
      had stronger sgACC FC with the left dorsolateral prefrontal cortex than the other
      groups. Our findings suggest that young males with IGD comorbid with depression
      have FC alterations of the default mode network and diminished FC with the
      prefrontal cortex. This altered FC pattern may be involved in the close
      association of IGD and depression.

PMID- 30233422
TI  - Burnout, Psychological Symptoms, and Secondary Traumatic Stress Among Midwives
      Working on Perinatal Wards: A Cross-Cultural Study Between Japan and Switzerland.
AB  - The aim of this study was to explore cross-cultural differences in symptoms of
      burnout, anxiety, depression, general psychological distress, and secondary
      traumatic stress between Asian (Japan) and European (Switzerland) midwives. One
      hundred seventy midwives participated in the study. There were significant
      differences in age group [chi2(3) = 24.2, p < 0.01], marital or relationship
      status [chi2(2) = 28.4, p < 0.01], and years of experience [chi2(2) = 17.8, p <
      0.01] between the two countries. The Japanese staff were younger, more often
      unmarried, and had less experience than the Swiss staff. The mean score of
      depersonalization was significantly higher in Switzerland (4.8 +/- 3.8) than in
      Japan (3.2 +/- 3.7; |z| = 2.71, p < 0.01). The mean score of general
      psychological distress in the Swiss sample (12.8 +/- 6.5) was significantly
      higher than that in the Japanese sample (10.3 +/- 6.2; |z| = 2.04, p = 0.04). In
      addition, the mean score of secondary traumatic stress was higher in the Swiss
      sample (31.8 +/- 9.7) than in the Japanese sample (24.1 +/- 8.6; |z| = 4.56, p <
      0.01). These results may reflect cultural differences such as working conditions
      or family environment between Japan and Switzerland.

PMID- 30233418
TI  - Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular
      Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis.
AB  - Diabetic patients suffer from a host of physiological abnormalities beyond just
      those of glucose metabolism. These abnormalities often lead to systemic
      inflammation via modulation of several inflammation-related genes, their
      respective gene products, homocysteine metabolism, and pyroptosis. The very
      nature of this homeostatic disruption re-sets the overall physiology of diabetics
      via upregulation of immune responses, enhanced retinal neovascularization,
      upregulation of epigenetic events, and disturbances in cells' redox regulatory
      system. This altered pathophysiological milieu can lead to the development of
      diabetic retinopathy (DR), a debilitating vision-threatening eye condition with
      microvascular complications. DR is the most prevalent cause of irreversible
      blindness in the working-age adults throughout the world as it can lead to severe
      structural and functional remodeling of the retina, decreasing vision and thus
      diminishing the quality of life. In this manuscript, we attempt to summarize
      recent developments and new insights to explore the very nature of this
      intertwined crosstalk between components of the immune system and their metabolic
      orchestrations to elucidate the pathophysiology of DR. Understanding the
      multifaceted nature of the cellular and molecular factors that are involved in DR
      could reveal new targets for effective diagnostics, therapeutics, prognostics,
      preventive tools, and finally strategies to combat the development and
      progression of DR in susceptible subjects.

PMID- 30233423
TI  - Haste or Speed? Alterations in the Impact of Incentive Cues on Task Performance
      in Remitted and Depressed Patients With Bipolar Disorder.
AB  - A variety of evidence suggests that bipolar disorder is associated with
      disruptions of reward related processes, although the properties, and scope of
      these changes are not well understood. In the present study, we aimed to address
      this question by examining performance of patients with bipolar disorder (30
      depressed bipolar; 35 euthymic bipolar) on a motivated choice reaction time task.
      We compared performance with a group of healthy control individuals (n = 44) and
      a group of patients with unipolar depression (n = 41), who were matched on
      several demographic variables. The task consists of an "odd-one-out"
      discrimination, in the presence of a cue signaling the probability of reward on a
      given trial (10, 50, or 90%) given a sufficiently fast response. All groups
      showed similar reaction time (RT) performance, and similar shortening of RT
      following the presentation of a reward predictive cue. However, compared to
      healthy individuals, the euthymic bipolar group showed a relative increase in
      commission errors during the high reward compared to low condition. Further
      correlational analysis revealed that in the healthy control and unipolar
      depression groups, participants tended either to shorten RTs for the high rather
      than low reward cue a relatively large amount with an increase in error rate, or
      to shorten RTs to a lesser extent but without increasing errors to the same
      degree. By contrast, reward-related speeding and reward-related increase in
      errors were less well coupled in the bipolar groups, significantly so in the BPD
      group. These findings suggest that although RT performance on the present task is
      relatively well matched, there may be a specific failure of individuals with
      bipolar disorder to calibrate RT speed and accuracy in a strategic way in the
      presence of reward-related stimuli.

PMID- 30233424
TI  - Hydrogen Sulfide Antagonizes Chronic Restraint Stress-Induced Depressive-Like
      Behaviors via Upregulation of Adiponectin.
AB  - Backgroud: Chronic restraint stress (CRS) induces depressive-like behaviors in
      rodents, which involves dysregulation of hippocampal synapse formation and
      excessive autophagy. Adiponectin has antidepressant activity. Hydrogen sulfide
      (H2S) is a novel gasotransmitter. The present work was to investigate whether H2S
      antagonizes CRS-induced depressive-like behaviors in rats and to explore whether
      its potential mechanism involves ameliorated synaptic and autophagic
      dysregulation by upregulation of adiponectin. Methods: Depressive-like behavior
      was analyzed by the tail suspension test (TST), novelty suppressed feeding test
      (NSFT), and open field test (OFT). The structure of autophagy was observed under
      transmission electron microscopy. The expressions of adiponectin, beclin1, and
      sequestosome 1 (p62/SQSTMI) protein in hippocampus were measured by Western blot.
      The levels of synapsin1 (SYN1) in the hippocampus were calculated by Western blot
      and immunofluorescence technique. Results: The behavior experiments, including
      TST, NSFT, and OFT, showed that NaHS (a donor of H2S) reduced CRS-induced
      depressive-like behaviors. NaHS decreased the loss of hippocampal synapse as
      evidenced by increased the level of SYN1 in the hippocampus of CRS-exposed rats.
      NaHS rescued CRS-induced excessive hippocampal autophagy as evidenced by declines
      in the number of autophagosomes and the expression of beclin1 as well as increase
      in the expression of P62 in the hippocampus of CRS-exposed rats. NaHS upregulated
      hippocampal adiponectin expression in the CRS-exposed rats. Furthermore,
      neutralizing adiponectin by Anti-acrp30 reversed the protective response of NaHS
      to CRS-produced depressive-like behaviors as well as hippocampal synaptic
      disruption and excessive autophagy. Conclusion: H2S mitigates CRS-induced
      depressive behavior via upregulation of adiponectin, which in turn results in
      amelioration in hippocampal synapse formation dysfunction and excessive
      autophagy.

PMID- 30233425
TI  - Clinical Characteristics, Life Adversities and Personality Traits in Monozygotic
      Twins With, at Risk of and Without Affective Disorders.
AB  - Background: Affective disorders have a long-term impact on psychiatric health and
      are caused by multiple interacting factors including familial risk, childhood
      adversity, life events and personality traits. Methods: In this study,
      monozygotic twins (MZ) at familial risk (indexed by affective disorder in their
      co-twin; high-risk group), affected MZ twins (indexed by a diagnosis with
      affective disorder) and MZ twins with no family history of affective disorder
      (low-risk group) were identified through cross-linking of nation-wide Danish
      registers. In total, 204 MZ twins were included and psychopathology, personality
      traits and life adversity were evaluated by semi-structured interviews and
      questionnaires. Results: Affected MZ twins presented with more subclinical
      affective symptoms and were functionally impaired as evidenced by higher
      unemployment rates and reduced functional status. The affected and the high-risk
      groups reported more childhood adversity and had experienced more stressful life
      events than the low-risk group. A direct comparison within the discordant twin
      pairs showed that the high-risk twins presented fewer affective symptoms, better
      functional status, more extraversion and lower neuroticism scores than their
      affected co-twins although they had equal levels of life adversity as their
      affected co-twins. Conclusion: These findings add to the evidence indicating that
      patients experience higher neuroticism, persistent subclinical symptoms and
      reduced socio-occupational function after affective episodes. Additionally,
      neuroticism and extraversion seem capable of moderating the sensitivity to
      exposure from the environment.

PMID- 30233426
TI  - Clonal Characteristics of T-Cell Receptor Repertoires in Violent and Non-violent
      Patients With Schizophrenia.
AB  - Background: Activated or impaired T-cell function in inflammatory and
      degenerative process can contribute to the risk and progression of schizophrenia.
      This study used immune repertoire sequencing to investigate the T-cell receptor
      beta variable chain (TRBV) presence in blood mononuclear cells in the violent or
      non-violent schizophrenic patients. Methods: Ten violent and 10 non-violent
      schizophrenic patients and 8 matched healthy controls were enrolled. The Brief
      Psychiatric Rating Scale (BPRS) was used to evaluate patients' psychiatric
      symptoms. The level of aggression was assessed using the Modified Overt
      Aggression Scale (MOAS). The complementarity-determining region 3 (CDR3) of TRBV
      was detected using multiplex-PCR and high-throughput sequencing. Results: The TCR
      repertoire diversity were no significant differences in the Shannon-Wiener or
      inverse Simpson diversity index between three groups. Principal component
      analysis (PCA) of TRBV composition and abundance showed that principal component
      1 and principal component 2 can explain 28.88 and 13.24% of total variation,
      respectively. Schizophrenic patients (violent and non-violent) had significantly
      different V gene distribution compared to healthy controls. In particular, TRBV2
      occurred at a significantly higher frequency in the violent schizophrenia group
      than in the non-violent schizophrenia and healthy control groups, and TRBV7-2
      occurred at a significantly higher frequency in the non-violent schizophrenia
      group than in the violent schizophrenia and healthy control groups. Conclusions:
      The results suggest that violent and non-violent schizophrenic patients carry
      abnormal T-cell receptor repertoires, and these data provide a useful clue to
      explore the etiology of violent behavior in schizophrenia.

PMID- 30233428
TI  - Yoga Practice Reduces the Psychological Distress Levels of Prison Inmates.
AB  - Background: Psychiatric ill-health is prevalent among prison inmates and often
      hampers their rehabilitation. Rehabilitation is crucial for reducing recidivistic
      offending. A few studies have presented evidence of the positive effect of yoga
      on the well-being of prison inmates. The conclusion of those previous studies
      that yoga is an effective method in the rehabilitation process of inmates, and
      deserves and requires further attention. Aims: The current study aimed to
      evaluate the effect of 10 weeks of yoga practice on the mental health profile,
      operationalized in the form of psychological distress, of inmates. Methods: One
      hundred and fifty-two volunteer participants (133 men; 19 women) were randomly
      placed in either of two groups: to participate in weekly 90-min yoga class (yoga
      group) or a weekly 90-min free-choice physical exercise (control group). The
      study period lasted for 10 weeks. Prior to and at the end of the study period the
      participants completed a battery of self-reported inventories, including the
      Brief Symptom Inventory (BSI). Results: Physical activity (including yoga)
      significantly reduced the inmates' levels of psychological distress. Yoga
      practice improved all primary symptom dimensions and its positive effect on the
      obsessive-compulsive, paranoid ideation, and somatization symptom dimensions of
      the BSI stayed significant even when comparing with the control group.
      Conclusions: Yoga as a form of physical activity is effective for reducing
      psychological distress levels in prison inmates, with specific effect on symptoms
      such as suspicious and fearful thoughts about losing autonomy, memory problems,
      difficulty in making decisions, trouble concentrating, obsessive thought, and
      perception of bodily dysfunction.

PMID- 30233427
TI  - Component Model of Addiction Treatment: A Pragmatic Transdiagnostic Treatment
      Model of Behavioral and Substance Addictions.
AB  - Behavioral addictions such as gambling, video games, sex, and shopping share many
      clinical features with substance use addictions including etiology, course, and
      neurobiology. Yet, the treatment of behavioral and substance use addictions tends
      to be separated. However, we argue that a more effective and efficient treatment
      approach is to conceptualize behavioral and substance use addictions as different
      expressions of a common underlying disorder and, in treatment, to address the
      underlying mechanisms common to both. To this end, the article presents a
      developing transdiagnostic treatment model of addictions that targets underlying
      similarities between behavioral and substance use addictions, called the
      component model of addiction treatment (CMAT). The CMAT is transdiagnostic in
      that it can be used in the treatment of both behavioral and substance use
      addictions. It is pragmatic in that it targets component vulnerabilities, which
      are enduring, yet malleable, individual psychological, cognitive, and
      neurobiological characteristics that are common to all addictive disorders and
      have been demonstrated to be modifiable. A working model of CMAT is presented,
      including proposed component vulnerabilities: lack of motivation, urgency,
      maladaptive expectancies, deficits in self-control, deficits in social support,
      and compulsivity, as well as their potential intervention possibilities. Future
      directions and potential implications of the CMAT are discussed.

PMID- 30233429
TI  - Association Between Trust and Mental, Social, and Physical Health Outcomes in
      Veterans and Active Duty Service Members With Combat-Related PTSD Symptomatology.
AB  - Background: Trust represents a complex emotion and interpersonal concept which
      assumes abandoning control over a given situation or set of circumstances, in
      turn yielding such control to another party. Advances in our knowledge of post
      traumatic stress disorder and moral injury have underscored the need to more
      closely examine how trust stands to impact health outcomes in these disorders.
      The aim of the present study is to examine and identify relationships linking
      general trust with select health outcomes in a mixed sample of Veterans and
      Service members with a self-reported history of deployment to a combat theater
      and PTSD symptomatology. Methods: This study applied a cross-sectional
      methodology, surveying n = 427 participants recruited across six sites. This
      included 373 Veterans and 54 active duty Service members in the United States.
      Measures included demographic characteristics, combat exposure, general trust,
      post-traumatic stress disorder symptomatology, depressive/anxiety symptomatology,
      alcohol use, social involvement, religiosity, and physical health. Data were
      analyzed descriptively as well as using Pearson correlations, Student's t-test,
      and multivariate regression. Results: Several significant relationships were
      identified, indicating an inverse relationship between trust and PTSD,
      depressive, and anxiety symptomatology. Greater levels of trust were also
      significantly associated with increased social interaction and religiosity.
      Lastly, no significant associations were identified with either physical
      functioning or pain level. Conclusion: The findings suggest that trust is
      correlated with a variety of health outcomes in Veterans and Service members
      affected by combat-related PTSD. Additional, hypothesis-driven research, informed
      by longitudinal data, is needed to better understand how trust stands to impact
      health outcomes, including the development of strategies and intervention options
      for repairing trust.

PMID- 30233432
TI  - Application of Intelligent Recommendation Techniques for Consumers' Food Choices
      in Restaurants.
AB  - Currently, there has been a new trend in applying modern robotics, information
      technology, and artificial intelligence to restaurants for improvements of food
      service, cost-effectiveness, and customer satisfaction. As robots replace humans
      to serve food, there is a clear need for robotic servers to help consumers select
      foods from a menu that satisfies their preferences such as taste and nutrition.
      However, currently, little is known about how eating behaviors drive food
      choices, and it is often difficult for consumers to make choices from a variety
      of foods offered by the typical restaurant, even with the assistance from a human
      server. In this paper, we conduct an exploratory study on an intelligent food
      choice method that recommends dishes by predicting individual's dietary
      preference, including ingredients, types of spices, price, etc. A multi-attribute
      relation matrix tri-factorization (MARMTF) technique is developed for a relation
      driven food recommendation system. First, the user's ordering history and their
      rating scores of the foods in the menu are gathered and represented by a user
      dish rating matrix. Next, the attribute relations of the ingredients, spicy
      level, and price of each food choice are extracted to construct a group of the
      relation matrices. Then, these matrices are integrated into a large block matrix.
      In the next step, a matrix tri-factorization algorithm is employed to decompose
      the block matrix and fuse the complex relationships into matrix factors. Further,
      a set of approximation block matrices are constructed and the predicted food
      rating matrix is generated. Finally, the foods (dishes) with sufficiently high
      preference scores are recommended to the consumers. Our experiments demonstrate
      that the MARMTF technique can provide effective dish recommendation for
      customers. Our system significantly simplifies the daunting task of making food
      choices and has a great potential in providing intelligent and professionally
      trained non-human waiters and waitresses for employment by future restaurants.

PMID- 30233431
TI  - Neurometabolite Levels in Alcohol Use Disorder Patients During Baclofen Treatment
      and Prediction of Relapse to Heavy Drinking.
AB  - Background and Aims: Baclofen, a GABAB agonist, is used as a treatment for
      alcohol dependence. We aimed to examine brain metabolites following
      administration of baclofen or placebo in alcohol dependent individuals enrolled
      in a randomized placebo-controlled trial. Methods: Participants included 31
      alcohol dependent individuals (recent drinking: N = 16; and abstinent: N = 15)
      who had received daily baclofen (BAC 30-75 mg = 20) or placebo (PL = 11) for at
      least 2 weeks (average 17 days). Using in vivo proton magnetic resonance
      spectroscopy (1H-MRS), spectra from the right parietal lobe were analyzed to
      obtain measures of GABA, Glutamate (Glu), Glutathione (GSH) and N-Acetyl Apartate
      (NAA) 120 min following administration of PL or BAC. Results: When weighting
      alcohol dependent participants according to recent alcohol consumption (within 24
      h), there were significant differences between BAC and PL on parietal
      concentrations of GSH (p < 0.01) and NAA (p < 0.05). Multiple linear regression
      revealed a significant predictive effect of GSH on heavy drinking days at 12
      weeks follow-up (Model: F = 14.28, R2 = 0.85; GSH: B = -1.22, p = 0.01) and also
      percentage days abstinent at 12 weeks follow-up (Model: F = 6.50, R2 = 0.72; GSH:
      B = 0.99, p = 0.06). Conclusion: Our data provide preliminary evidence that the
      effect of baclofen may be mediated by increased parietal concentrations of the
      antioxidant GSH and NAA in recently drinking alcohol dependent patients. GSH/Cr
      levels were also predictive of improved drinking outcomes in the trial and
      suggests a role for neural oxidative stress in alcohol use disorder.

PMID- 30233433
TI  - How to Manage Self-Poisoning With Baclofen in Alcohol Use Disorder? Current
      Updates.
AB  - Specialists in addiction medicine continue to debate whether baclofen is still
      indicated to treat alcohol use disorders in view of conflicting results as to its
      efficacy. This review summarizes current knowledge on self-poisoning with
      baclofen focusing of alcohol-use disorder in order to provide an overview of the
      reliable scientific knowledge on management of such an intoxication. Moreover, as
      alcohol-dependent patients experience many psychiatric co-morbidities, the risk
      in suicide attempt using baclofen seems real. Numerous studies have suggested
      that patients given daily-doses of baclofen higher than 80 mg/day are more likely
      to attempt suicides than others. Following an ingestion of a large amount of
      baclofen, central nervous system depression is usually observed. Seizures require
      the patient to be admitted in intensive care unit and should be treated like
      other toxicological seizures. Cardiac complications include prolonged QTc
      interval, degree heart block, premature atrial contractions, and supraventricular
      tachycardia, hypotension and bradycardia. In cases of intoxication, the
      elimination half-life of baclofen may last between 12 and 36 h post-overdose and
      renal failure is known to delay its clearance. Rarely measured in clinical
      practice, the toxic level of baclofen blood level ranges from 1.1 to 3.5 mg/l,
      and coma or fatal intoxication are observed from 6 to 9.6 mg/l. Baclofen
      withdrawal has been observed but making the diagnosis of withdrawal in case of
      suspected self-poisoning is difficult as baclofen intoxication and baclofen
      withdrawal share many clinical signs. Admission to hospital to manage of suicide
      attempt with baclofen is mandatory and should not be limited to baclofen alone.
      It needs to include other aspects of the overall care of patients with alcohol
      disorders (psychological and psychosocial interventions, management of comorbid
      mental conditions and physical complications).

PMID- 30233434
TI  - Age-Related Differences in Alcohol Intake and Control Over Alcohol Seeking in
      Rats.
AB  - Alcohol use disorder (AUD) is characterized by excessive and persistent alcohol
      use, despite adverse consequences. AUD often originates during adolescence, as do
      other substance use disorders. However, despite periods of excessive alcohol
      intake, many adolescents reduce their alcohol use by early adulthood. Brain
      development, social context, personality traits, and genetic makeup are thought
      to play an important role in these age-dependent fluctuations in alcohol use.
      However, studies that directly investigate age-related differences in the effects
      of alcohol exposure on brain and behavior are sparse. Therefore, to better
      understand the relationship between adolescent alcohol consumption and AUD-like
      behavior, this study compared the degree of control over alcohol seeking in rats
      that differed in terms of age of onset of alcohol drinking and in their level of
      alcohol consumption. We hypothesized that control over alcohol seeking is more
      prominent in adolescent-onset rats than in adult-onset rats, and that control
      over alcohol seeking is related to the consumed amount of alcohol. To test this
      hypothesis, alcohol seeking in the presence of a conditioned aversive stimulus
      was assessed after 2 months of intermittent alcohol access (IAA) in rats that
      consumed alcohol from postnatal day 42 (adolescence) or day 77 (adulthood). The
      rats were subdivided into low (LD), medium (MD), or high (HD) alcohol drinking
      rats, in order to assess the impact of the extent of alcohol intake on control
      over alcohol seeking. The adolescent-onset animals consumed slightly, but
      significantly less alcohol compared to the adult-onset rats. In adult-onset rats,
      we found that conditioned suppression of alcohol seeking, i.e., reduction of
      alcohol seeking by presentation of a conditioned aversive stimulus, was most
      pronounced in LD. By contrast, in the adolescent-onset rats, MD and HD showed
      increased alcohol seeking compared to LD, which was suppressed by conditioned
      aversive stimuli. Taken together, these findings reveal a complex relationship
      between the age of onset and level of alcohol intake with control over alcohol
      seeking, whereby adolescent rats consume less alcohol than adults. In adult rats,
      control over alcohol seeking is negatively related to preceding levels of alcohol
      intake. By contrast, adolescent rats appear to retain control over alcohol
      seeking, even after a history of high levels of alcohol intake.

PMID- 30233436
TI  - Prior Knowledge, Episodic Control and Theory of Mind in Autism: Toward an
      Integrative Account of Social Cognition.
AB  - Over the last 30 years, research has explored theory of mind (ToM), the ability
      to attribute mental states to oneself and to others. Work on ToM in typical and
      atypical populations has shed light on the neurocognitive mechanisms underlying
      social understanding and interaction. The ToM hypothesis has long been regarded
      as one comprehensive explanation of the severe cognitive and behavioral
      impairments encountered by individuals with autism. However, high-functioning
      individuals can often pass both first-order and second-order false belief tasks
      using cognitive compensation strategies. To provide more sensitive measures of
      mental state attribution abilities, researchers have introduced more difficult,
      "advanced" theory of mind tasks. In this article, we argue that in attempting to
      bypass compensation strategies, these new advanced ToM tasks, such as the Faux
      Pas and the Strange Stories tasks, impose cognitive demands beyond those specific
      to the domain of ToM. We then provide an integrative account of social deficits
      in autism that takes into account several distinct components of mental state
      understanding, including both general cognitive capacities and processes specific
      to ToM. We argue that a number of related cognitive abilities, including episodic
      cognitive control and inferencing from prior knowledge, are necessary to
      understand how both people with autism and typical development navigate
      challenging, real-life social situations.

PMID- 30233437
TI  - Assessing Construct Validity in Math Achievement: An Application of Multilevel
      Structural Equation Modeling (MSEM).
AB  - The purpose of the present study was to model math achievement at both the person
      and university levels of the analyses in order to understand the optimal factor
      structure of math competency. Data involved 2,881 students who took a national
      mathematics examination as part of their entry at the university public system in
      Saudi Arabia. Four factors from the National math examination comprised the math
      achievement measure, namely, numbers and operations, algebra and analysis,
      geometry and measurement, and, statistics and probabilities. Data were analyzed
      using the aggregate method and by use of Multilevel Structural Equation Modeling
      (MSEM). Results indicated that both a unidimensional and a 4-factor correlated
      model fitted the data equally well using aggregate data, where for reasons of
      parsimony the unidimensional model was the preferred choice with these data. When
      modeling data including clustering, results pointed to alternative factor
      structures at the person and university levels. Thus, a unidimensional model
      provided the best fit at the University level, whereas a four-factor correlated
      model was most descriptive for person level data. The optimal simple structure
      was evaluated using the Ryu and West (2009) methodology for partially saturating
      the MSEM model and also met criteria for discriminant validation as described in
      Gorsuch (1983). Furthermore, a university level variable, namely the year of
      establishment, pointed to the superiority of older institutions with regard to
      math achievement. It is concluded that ignoring a multilevel structure in the
      data may result in erroneous conclusions with regard to the optimal factor
      structure and the tests of structural models following that.

PMID- 30233438
TI  - Applicability of the Movement Assessment Battery for Children-Second Edition
      (MABC-2) for Japanese Children Aged 3-6 Years: A Preliminary Investigation
      Emphasizing Internal Consistency and Factorial Validity.
AB  - This study investigated the applicability of the Movement Assessment Battery for
      Children - Second Edition (MABC-2) for 3- to 6-year-old Japanese children,
      particularly addressing its internal consistency and factorial validity. The MABC
      2 test set for 3- to 6-year-old children was administered to 252 children.
      Differences between Japanese children and those of the original normative sample
      (i.e. United Kingdom children) were investigated along with sex differences. The
      Japanese children aged 3-6 years were found to have higher Manual Dexterity and
      Balance component scores than children of the normative sample. Girls scored
      higher than boys on the Balance component. Results of several analyses showed
      good internal consistency of the MABC-2. Confirmatory factor analysis revealed
      that a theoretical three-component model of the MABC-2 was not fitted to Japanese
      children aged 3-6 years. Instead, a new three-component model was postulated and
      discussed. The new three-component model of the MABC-2, with Manual Dexterity,
      Static Balance and Ball Skills, and Dynamic Balance, has high factorial validity
      in Japanese children aged 3-6 years.

PMID- 30233435
TI  - Adverse Childhood Experiences and the Consequences on Neurobiological,
      Psychosocial, and Somatic Conditions Across the Lifespan.
AB  - Introduction: Adverse childhood experiences (ACE) such as sexual and physical
      abuse or neglect are frequent in childhood and constitute a massive stressor with
      long-lasting adverse effects on the brain, mental and physical health.The aim of
      this qualitative review is to present a concise overview of the present
      literature on the impact of ACE on neurobiology, mental and somatic health in
      later adulthood. Methods: The authors reviewed the existing literature on the
      impact of ACE on neurobiology, mental and somatic health in later adulthood and
      summarized the results for a concise qualitative overview. Results: In adulthood,
      the history of ACE can result in complex clinical profiles with several co
      occurring mental and somatic disorders such as posttraumatic stress disorder,
      depression, borderline personality disorder, obesity and diabetes. Although a
      general stress effect in the development of the disorders and neural alterations
      can be assumed, the role of type and timing of ACE is of particular interest in
      terms of prevention and treatment of ACE-related mental and somatic conditions.
      It has been suggested that during certain vulnerable developmental phases the
      risk for subsequent ACE-related disorders is increased. Moreover, emerging
      evidence points to sensitive periods and specificity of ACE-subtypes in the
      development of neurobiological alterations, e.g., volumetric and functional
      changes in the amygdala and hippocampus. Conclusion: Longitudinal studies are
      needed to investigate complex ACE-related characteristics and mechanisms relevant
      for mental and somatic disorders by integrating state of the art knowledge and
      methods. By identifying and validating psychosocial and somatic risk factors and
      diagnostic markers one might improve the development of innovative somatic and
      psychological treatment options for individuals suffering from ACE-related
      disorders.

PMID- 30233430
TI  - Parallels and Overlap: The Integration of Homeostatic Signals by Mesolimbic
      Dopamine Neurons.
AB  - Motivated behaviors are often initiated in response to perturbations of
      homeostasis. Indeed, animals and humans have fundamental drives to procure
      (appetitive behaviors) and eventually ingest (consummatory behaviors) substances
      based on deficits in body fluid (e.g., thirst) and energy balance (e.g., hunger).
      Consumption, in turn, reinforces motivated behavior and is therefore considered
      rewarding. Over the years, the constructs of homeostatic (within the purview of
      the hypothalamus) and reward (within the purview of mesolimbic circuitry) have
      been used to describe need-based vs. need-free consumption. However, many
      experiments have demonstrated that mesolimbic circuits and "higher-order" brain
      regions are also profoundly influenced by changes to physiological state, which
      in turn generate behaviors that are poised to maintain homeostasis. Mesolimbic
      pathways, particularly dopamine neurons of the ventral tegmental area (VTA) and
      their projections to nucleus accumbens (NAc), can be robustly modulated by a
      variety of energy balance signals, including post-ingestive feedback relaying
      nutrient content and hormonal signals reflecting hunger and satiety. Moreover,
      physiological states can also impact VTA-NAc responses to non-nutritive rewards,
      such as drugs of abuse. Coupled with recent evidence showing hypothalamic
      structures are modulated in anticipation of replenished need, classic boundaries
      between circuits that convey perturbations in homeostasis and those that drive
      motivated behavior are being questioned. In the current review, we examine data
      that have revealed the importance of mesolimbic dopamine neurons and their
      downstream pathways as a dynamic neurobiological mechanism that provides an
      interface between physiological state, perturbations to homeostasis, and reward
      seeking behaviors.

PMID- 30233439
TI  - Interpersonal Synchronization, Motor Coordination, and Control Are Impaired
      During a Dynamic Imitation Task in Children With Autism Spectrum Disorder.
AB  - Background: Impairments in imitation abilities have been commonly described in
      children with autism spectrum disorder (ASD). How motricity in interpersonal
      coordination impacts imitation, during long lasting semi-ecological conditions,
      has not been carefully investigated. Methods: Eighty-five children and
      adolescents (39 controls with typical development, TD; 29 patients with ASD; 17
      patients with developmental coordination disorder, DCD), aged 6 to 20 years,
      participated to a behavioral paradigm in which participants, standing and moving,
      interacted with a virtual tightrope walker standing and moving as well. During
      the protocol, we measured automatically and continuously bodily postures and
      movements from RGB sensor recording to assess participants' behavioral imitation.
      Results: We show that (1) interpersonal synchronization (as evidenced by the
      synchrony between the participant's and the tightrope walker's bars) and (2)
      motor coordination (as evidenced by the synchrony between the participant's bar
      and its own head axis) increased with age and were more impaired in patients with
      ASD. Also, motor control as evidenced by the movement angle standard deviations
      of participants' bar and head were significantly impaired in ASD compared to TD
      or DCD. Conclusion: Interpersonal synchronization and motor coordination during
      ecological interaction show both subtle impairment in children with ASD as
      compared to children with TD or DCD. These results questioned how motricity
      mature in terms of motor control and proprioception in children with ASD.

PMID- 30233441
TI  - The Psychology of Uncertainty and Three-Valued Truth Tables.
AB  - Psychological research on people's understanding of natural language connectives
      has traditionally used truth table tasks, in which participants evaluate the
      truth or falsity of a compound sentence given the truth or falsity of its
      components in the framework of propositional logic. One perplexing result
      concerned the indicative conditional if A then C which was often evaluated as
      true when A and C are true, false when A is true and C is false but irrelevant"
      (devoid of value) when A is false (whatever the value of C). This was called the
      "psychological defective table of the conditional." Here we show that far from
      being anomalous the "defective" table pattern reveals a coherent semantics for
      the basic connectives of natural language in a trivalent framework. This was done
      by establishing participants' truth tables for negation, conjunction,
      disjunction, conditional, and biconditional, when they were presented with
      statements that could be certainly true, certainly false, or neither. We review
      systems of three-valued tables from logic, linguistics, foundations of quantum
      mechanics, philosophical logic, and artificial intelligence, to see whether one
      of these systems adequately describes people's interpretations of natural
      language connectives. We find that de Finetti's (1936/1995) three-valued system
      is the best approximation to participants' truth tables.

PMID- 30233440
TI  - Children's Relationship With Their Pet Dogs and OXTR Genotype Predict Child-Pet
      Interaction in an Experimental Setting.
AB  - Human-animal interaction (HAI) research has increasingly documented the important
      role of pet dogs in children's lives. The quality of interaction between children
      and their pet dogs, however, is likely influenced by individual differences among
      children as well as their perceived relationship with their pet dog. Ninety-seven
      children aged 7-12 years and their pet dogs participated in a laboratory protocol
      during which the child solicited interaction with their dog, from which time
      petting and gazing were recorded. Children reported on their perceived
      relationship with the pet dog via interview. Children provided saliva samples,
      from which a polymorphism in the oxytocin receptor, OXTR rs53576, which has long
      been implicated in social behavior, was genotyped. The results showed that OXTR
      genotype and children's perceived antagonism with the pet dog predicted the
      amount of petting, but not gazing, between children and their pet dogs. This
      research adds to the growing body of HAI research by documenting individual
      differences that may influence children's interactions with animals, which is key
      to research related to pet ownership and understanding factors that may impact
      therapeutic interventions involving HAI.

PMID- 30233442
TI  - Integrating Curriculum-Based Dynamic Assessment in Computerized Adaptive Testing:
      Development and Predictive Validity of the EDPL-BAI Battery on Reading
      Competence.
AB  - In recent decades there have been significant changes in the conceptualization of
      reading as well as in the perception of how this activity should be assessed.
      Interest in the analysis of reading processes has led to the emergence of new
      explanatory models based primarily on the contributions of cognitive psychology.
      In parallel, there have been notable advances in measurement procedures,
      especially in models based on Item Response Theory (IRT), as well as in the
      capacity and performance of specific software programs that allow data to be
      managed and analyzed. These changes have contributed significantly to the rise of
      testing procedures such as computerized adaptive tests (CATs), whose fundamental
      characteristic is that the sequence of items presented in the tests is adapted to
      the level of competence that the subject manifests. Likewise, the incorporation
      of elements of dynamic assessment (DA) as the prompts are gradually offered
      allows for obtaining information about the type and degree of support required to
      optimize the subject's performance. In this sense, the confluence of
      contributions from DA and CATs offers a new possibility for approaching the
      assessment of learning processes. In this article, we present a longitudinal
      research developed in two phases, through which a computerized dynamic adaptive
      assessment battery of reading processes (EDPL-BAI) was configured. The research
      frame involved 1,831 students (46% girls) from 13 public schools in three regions
      of Chile. The purpose of this study was to analyze the differential contribution
      on reading competence of dynamic scores obtained in a subsample composed of 324
      (47% girls) students from third to sixth grade after the implementation of a set
      of adaptive dynamic tests of morpho-syntactic processes. The results achieved in
      the structural equation modeling indicate a good global fit. Individual
      relationships show a significant contribution of calibrated score that reflects
      estimated knowledge level on reading competence, as well as dynamic scores based
      on the assigned value of graduated prompts required by the students. These
      results showed significant predictive values on reading competence and
      incremental validity in relation to predictions made by static criterion tests.

PMID- 30233443
TI  - 30 Days Wild and the Relationships Between Engagement With Nature's Beauty,
      Nature Connectedness and Well-Being.
AB  - Recent research suggests that engagement with natural beauty (EWNB) is key to the
      well-being benefits of nature connectedness. The Wildlife Trust's 30 Days Wild
      campaign provides a large-scale intervention for improving public engagement with
      nature and its beauty. The effect of 30 Days Wild participation on levels of EWNB
      and the relationship between EWNB, nature connectedness and happiness was
      evaluated during the 2017 campaign. Of the 49,000 people who signed up to the
      campaign, 308 people fully completed measures of EWNB, nature connection, health,
      happiness, and conservation behaviors at baseline, post-30 days and post-2
      months. There were sustained and significant increases for scores in nature
      connection, health, happiness, and conservation behaviors. In addition, 30 Days
      Wild was the first intervention found to increase EWNB. Further, the significant
      increase in EWNB mediated the relationship between the increases in nature
      connectedness and happiness. In a supplementary study to understand the well
      being benefits further (n = 153), emotional regulation was found to mediate the
      relationship between nature connectedness and happiness, but EWNB and emotional
      regulation were not related. The links between nature's beauty, nature
      connectedness and well-being are discussed within an account of affect
      regulation.

PMID- 30233444
TI  - Does Cognition Have a Role in Plasticity of "Innate Behavior"? A Perspective From
      Drosophila.

PMID- 30233446
TI  - Training Children to Perceive Non-native Lexical Tones: Tone Language Background,
      Bilingualism, and Auditory-Visual Information.
AB  - This study investigates the role of language background and bilingual status in
      the perception of foreign lexical tones. Eight groups of participants, consisting
      of children of 6 and 8 years from one of four language background (tone or non
      tone) * bilingual status (monolingual or bilingual)-Thai monolingual, English
      monolingual, English-Thai bilingual, and English-Arabic bilingual were trained to
      perceive the four Mandarin lexical tones. Half the children in each of these
      eight groups were given auditory-only (AO) training and half auditory-visual (AV)
      training. In each group Mandarin tone identification was tested before and after
      (pre- and post-) training with both auditory-only test (ao-test) and auditory
      visual test (av test). The effect of training on Mandarin tone identification was
      minimal for 6-year-olds. On the other hand, 8-year-olds, particularly those with
      tone language experience showed greater pre- to post-training improvement, and
      this was best indexed by ao-test trials. Bilingual vs. monolingual background did
      not facilitate overall improvement due to training, but it did modulate the
      efficacy of the Training mode: for bilinguals both AO and AV training, and
      especially AO, resulted in performance gain; but for monolinguals training was
      most effective with AV stimuli. Again this effect was best indexed by ao-test
      trials. These results suggest that tone language experience, be it monolingual or
      bilingual, is a strong predictor of learning unfamiliar tones; that monolinguals
      learn best from AV training trials and bilinguals from AO training trials; and
      that there is no metalinguistic advantage due to bilingualism in learning to
      perceive lexical tones.

PMID- 30233445
TI  - Neurochemistry Predicts Convergence of Written and Spoken Language: A Proton
      Magnetic Resonance Spectroscopy Study of Cross-Modal Language Integration.
AB  - Recent studies have provided evidence of associations between neurochemistry and
      reading (dis)ability (Pugh et al., 2014). Based on a long history of studies
      indicating that fluent reading entails the automatic convergence of the written
      and spoken forms of language and our recently proposed Neural Noise Hypothesis
      (Hancock et al., 2017), we hypothesized that individual differences in cross
      modal integration would mediate, at least partially, the relationship between
      neurochemical concentrations and reading. Cross-modal integration was measured in
      231 children using a two-alternative forced choice cross-modal matching task with
      three language conditions (letters, words, and pseudowords) and two levels of
      difficulty within each language condition. Neurometabolite concentrations of
      Choline (Cho), Glutamate (Glu), gamma-Aminobutyric (GABA), and N- acetyl
      aspartate (NAA) were then measured in a subset of this sample (n = 70) with
      Magnetic Resonance Spectroscopy (MRS). A structural equation mediation model
      revealed that the effect of cross-modal word matching mediated the relationship
      between increased Glu (which has been proposed to be an index of neural noise)
      and poorer reading ability. In addition, the effect of cross-modal word matching
      fully mediated a relationship between increased Cho and poorer reading ability.
      Multilevel mixed effects models confirmed that lower Cho predicted faster cross
      modal matching reaction time, specifically in the hard word condition. These Cho
      findings are consistent with previous work in both adults and children showing a
      negative association between Cho and reading ability. We also found two novel
      neurochemical relationships. Specifically, lower GABA and higher NAA predicted
      faster cross-modal matching reaction times. We interpret these results within a
      biochemical framework in which the ability of neurochemistry to predict reading
      ability may at least partially be explained by cross-modal integration.

PMID- 30233447
TI  - Forgiveness, Marital Quality, and Marital Stability in the Early Years of Chinese
      Marriage: An Actor-Partner Interdependence Mediation Model.
AB  - Based on the Vulnerability Stress Adaptation model, this study examined the
      relationship between forgiveness and marital stability, and provides a first look
      at the mediating role of marital quality in this association during the first 3
      years of marriage based on three annual waves of data collected from 268 Chinese
      couples. Tests of actor-partner interdependence mediation models revealed direct
      effects of decisional forgiveness and emotional forgiveness on the concurrent
      levels of marital stability for husbands, and indirect effects of emotional
      forgiveness on the concurrent and longitudinal levels of marital stability
      through marital quality for both husbands and wives. There was also an indirect
      effect of wives' emotional forgiveness on concurrent and longitudinal levels of
      husbands' marital stability through their wives' marital quality. Thus, emotional
      forgiveness, rather than decisional forgiveness, contributes to longitudinal
      levels of marital stability through marital quality. Theoretical implications and
      future directions for research are discussed.

PMID- 30233449
TI  - Good Things for Those Who Wait: Predictive Modeling Highlights Importance of
      Delay Discounting for Income Attainment.
AB  - Income is a primary determinant of social mobility, career progression, and
      personal happiness. It has been shown to vary with demographic variables like age
      and education, with more oblique variables such as height, and with behaviors
      such as delay discounting, i.e., the propensity to devalue future rewards.
      However, the relative contribution of each these salary-linked variables to
      income is not known. Further, much of past research has often been underpowered,
      drawn from populations of convenience, and produced findings that have not always
      been replicated. Here we tested a large (n = 2,564), heterogeneous sample, and
      employed a novel analytic approach: using three machine learning algorithms to
      model the relationship between income and age, gender, height, race, zip code,
      education, occupation, and discounting. We found that delay discounting is more
      predictive of income than age, ethnicity, or height. We then used a holdout data
      set to test the robustness of our findings. We discuss the benefits of our
      methodological approach, as well as possible explanations and implications for
      the prominent relationship between delay discounting and income.

PMID- 30233448
TI  - Informal Caregiving Relationships in Psychosis: Reviewing the Impact of Patient
      Violence on Caregivers.
AB  - A modest association can be found between people with a schizophrenia spectrum
      diagnosis (psychosis) and perpetrating acts of violence. When a person with
      psychosis does engage in violence, it is their informal carers, when compared to
      those from the general population, who are more likely to be the targets, and
      violence will often occur within the family home. Despite the importance of carer
      support for improving patient outcomes, our understanding of how carers are
      impacted by patient initiated violence in psychosis remains limited. This paper
      reviews literature documenting the effects of patient-initiated violence in
      psychosis on carer functioning. The review comprised searches of Medline,
      PsychInfo, Embase, and Web of Science databases and the hand searches of
      reference lists from relevant published papers. The review was limited to English
      language publications from inception to 11th September 2017, and where carer
      experiences following reports of violence from patients with psychosis were
      specifically recorded. Data from 20 papers using mixed methodologies were
      reviewed. Patient violence in psychosis was linked to poorer carer outcomes,
      including carer reports of burden, trauma, fear, and helplessness. There is,
      however, a significant need for further studies to systematically quantify the
      impact and correlates of patient initiated violence on psychosis caregivers, and
      improve prevention.

PMID- 30233451
TI  - A Neural Network Framework for Cognitive Bias.
AB  - Human decision-making shows systematic simplifications and deviations from the
      tenets of rationality ('heuristics') that may lead to suboptimal decisional
      outcomes ('cognitive biases'). There are currently three prevailing theoretical
      perspectives on the origin of heuristics and cognitive biases: a cognitive
      psychological, an ecological and an evolutionary perspective. However, these
      perspectives are mainly descriptive and none of them provides an overall
      explanatory framework for the underlying mechanisms of cognitive biases. To
      enhance our understanding of cognitive heuristics and biases we propose a neural
      network framework for cognitive biases, which explains why our brain
      systematically tends to default to heuristic ('Type 1') decision making. We argue
      that many cognitive biases arise from intrinsic brain mechanisms that are
      fundamental for the working of biological neural networks. To substantiate our
      viewpoint, we discern and explain four basic neural network principles: (1)
      Association, (2) Compatibility, (3) Retainment, and (4) Focus. These principles
      are inherent to (all) neural networks which were originally optimized to perform
      concrete biological, perceptual, and motor functions. They form the basis for our
      inclinations to associate and combine (unrelated) information, to prioritize
      information that is compatible with our present state (such as knowledge,
      opinions, and expectations), to retain given information that sometimes could
      better be ignored, and to focus on dominant information while ignoring relevant
      information that is not directly activated. The supposed mechanisms are
      complementary and not mutually exclusive. For different cognitive biases they may
      all contribute in varying degrees to distortion of information. The present
      viewpoint not only complements the earlier three viewpoints, but also provides a
      unifying and binding framework for many cognitive bias phenomena.

PMID- 30233450
TI  - Social Capital as a Moderator of the Relationship Between Perceived
      Discrimination and Alcohol and Cannabis Use Among Immigrant and Non-immigrant
      Adolescents in Israel.
AB  - Literature highlights the relationship between perceived discrimination and
      frequency and severity of alcohol and cannabis use. One mechanism for explaining
      this is the nature of perceived discrimination as a potentially traumatic
      interpersonal stressor, which can lead to the depletion of social and personal
      resources. Within a Recovery Capital (RC) framework, the current study explores
      whether the existence of social capital in the form of parental monitoring,
      friend and teacher support can buffer the relationship between perceived
      discrimination and alcohol and cannabis use among immigrant and non-immigrant
      adolescents, by replenishing the depleted resources. The study included a
      representative sample of 8,598 students in Israel, aged 11-18, from the Health
      Behaviors of School Aged Children (HBSC) 2013-2014 data: 1503 immigrant
      adolescents from the Former Soviet Union [FSU] (N = 955) and Ethiopia (N = 548)
      and 7086 non-immigrants. Results confirmed that perceived discrimination was
      positively related to substance use; all three forms of social capital were
      negatively related to alcohol and cannabis use and moderated the relationship
      between perceived discrimination and substance use, with the exception of friend
      support in the case of alcohol use. When all three social capital measures were
      included together, the adult social capital measures were significant predictors
      of substance use. Results suggest that levels of social capital, especially as
      provided by parents and teachers, can help young people, both immigrant and
      majority group adolescents, to cope with perceived discrimination.

PMID- 30233452
TI  - Dual Task Effects on Visual Attention Capacity in Normal Aging.
AB  - Older adults show higher dual task performance decrements than younger adults.
      While this is assumed to be related to attentional capacity reductions, the
      precise affected functions are not specified. Such specification is, however,
      possible based on the "theory of visual attention" (TVA) which allows for
      modeling of distinct attentional capacity parameters. Furthermore, it is unclear
      whether older adults show qualitatively different attentional effects or whether
      they show the same effects as younger adults experience under more challenging
      conditions. By varying the complexity of the secondary task, it is possible to
      address this question. In our study, participants performed a verbal whole report
      of briefly presented letter arrays. TVA-based fitting of report performance
      delivered parameters of visual threshold t0, processing speed C, and visual short
      term memory (VSTM) storage capacity K. Furthermore, participants performed a
      concurrent motor task consisting of continuous tapping of a (simple or complex)
      sequence. Both TVA and tapping tasks were performed under single and dual task
      conditions. Two groups of 30 younger adults each performed either the simple or
      complex tapping, and a group of 30 older adults performed the simple tapping
      condition. In older participants, VSTM storage capacity declined under dual task
      conditions. While no such effect was found in younger subjects performing the
      simple tapping sequence under dual task conditions, the younger group performing
      the complex tapping task under dual task conditions also showed a significant
      VSTM capacity reduction. Generally, no significant effect on other TVA parameters
      or on tapping accuracy was found. Comparable goodness-of-fit measures were
      obtained for the TVA modeling data in single and dual tasks, indicating that
      tasks were executed in a qualitatively similar, continuous manner, although
      quantitatively less efficiently under dual- compared to single-task conditions.
      Taken together, our results show that the age-specific effects of motor-cognitive
      dual task interference are reflected by a stronger decline of VSTM storage
      capacity. They support an interpretation of VSTM as central attentional capacity,
      which is shared across visual uptake and concurrent motor performance. Capacity
      limits are reached earlier, and already under lower motor task complexity, in
      older compared to younger adults.

PMID- 30233453
TI  - Commentary on "Interaction in Spoken Word Recognition Models".

PMID- 30233454
TI  - Intimate Partner Violence in the Golden Age: Systematic Review of Risk and
      Protective Factors.
AB  - Intimate partner violence (IPV) is identifiable as a major public health concern
      worldwide. The international literature highlights how this phenomenon is complex
      and transversal to all age groups. While the global population is becoming older,
      the scientific research about risk and protective factors related to IPV in the
      golden age is diverse, and the different findings of the various studies have not
      been systematized so far. Thus, in this systematic review, we aim to analyze the
      scientific studies that investigate the risk and the protective factors of
      violent dynamics between elderly couples. From the perspective of the theoretical
      frameworks and the methodological approaches used, we present the main conceptual
      themes that emerge. Following the guidelines of the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses statement, we review the articles that
      report the analyses of protective and risk factors of IPV perpetration. Our
      results indicate social support, help-seeking behavior, and the availability of
      community-based services addressing the issues of abuse as the main protective
      factors. The risk factors are related to economic conditions, belonging to an
      ethnic minority, cognitive or physical impairment, other conditions associated
      with cultural background and relational dynamics, such as intrapartner dependence
      and intergenerational transmission of violence and trauma, and caregiving stress.
      We discuss possible future directions of research to improve the understanding of
      IPV in the elderly population and the implications for the development of
      intervention policies at preventive and supportive levels.

PMID- 30233456
TI  - Bumblebees Express Consistent, but Flexible, Speed-Accuracy Tactics Under
      Different Levels of Predation Threat.
AB  - A speed-accuracy trade-off (SAT) in behavioural decisions is known to occur in a
      wide range of vertebrate and invertebrate taxa. Accurate decisions often take
      longer for a given condition, while fast decisions can be inaccurate in some
      tasks. Speed-accuracy tactics are known to vary consistently among individuals,
      and show a degree of flexibility during colour discrimination tasks in bees. Such
      individual flexibility in speed-accuracy tactics is likely to be advantageous for
      animals exposed to fluctuating environments, such as changes in predation threat.
      We therefore test whether individual speed-accuracy tactics are fixed or flexible
      under different levels of predation threat in a model invertebrate, the bumblebee
      Bombus terrestris. The flexibility of speed-accuracy tactics in a foraging
      context was tested in the laboratory using a "meadow" of artificial flowers
      harbouring "robotic" crab spider predators. We found that while the ranking of
      bees along the speed and accuracy continuums was consistent across two levels of
      predation threat, there was some flexibility in the tactics used by individual
      bees - most bees became less accurate at colour discrimination when exposed to
      predation threat when flower types were rewarding. The relationship between
      decision speed and accuracy was influenced by predator detectability and the risk
      associated with making incorrect choices during the colour discrimination task.
      Predator crypsis resulted in a breakdown in the relationship between speed and
      accuracy, especially when making an incorrect floral choice incurred a
      distasteful quinine punishment. No single speed-accuracy tactic was found to be
      optimal in terms of foraging efficiency under either predation threat situation.
      However, bees that made faster decisions achieved higher nectar collection rates
      in predator free situations, while accurate bees achieved higher foraging rates
      under predation threat. Our findings show that while individual bees remain
      relatively consistent in terms of whether they place greater emphasis on speed or
      accuracy under predation threat, they can respond flexibly to the additional time
      costs of detecting predators.

PMID- 30233455
TI  - The Relationship Between Resting State Network Connectivity and Individual
      Differences in Executive Functions.
AB  - The brain is organized into a number of large networks based on shared function,
      for example, high-level cognitive functions (frontoparietal network), attentional
      capabilities (dorsal and ventral attention networks), and internal mentation
      (default network). The correlations of these networks during resting-state fMRI
      scans varies across individuals and is an indicator of individual differences in
      ability. Prior work shows higher cognitive functioning (as measured by working
      memory and attention tasks) is associated with stronger negative correlations
      between frontoparietal/attention and default networks, suggesting that increased
      ability may depend upon the diverging activation of networks with contrasting
      function. However, these prior studies lack specificity with regard to the higher
      level cognitive functions involved, particularly with regards to separable
      components of executive function (EF). Here we decompose EF into three factors
      from the unity/diversity model of EFs: Common EF, Shifting-specific EF, and
      Updating-specific EF, measuring each via factor scores derived from a battery of
      behavioral tasks completed by 250 adult participants (age 28) at the time of a
      resting-state scan. We found the hypothesized segregated pattern only for
      Shifting-specific EF. Specifically, after accounting for one's general EF ability
      (Common EF), individuals better able to fluidly switch between task sets have a
      stronger negative correlation between the ventral attention network and the
      default network. We also report non-predicted novel findings in that individuals
      with higher Shifting-specific abilities exhibited more positive connectivity
      between frontoparietal and visual networks, while those individuals with higher
      Common EF exhibited increased connectivity between sensory and default networks.
      Overall, these results reveal a new degree of specificity with regard to
      connectivity/EF relationships.

PMID- 30233457
TI  - Domestic Violence in Separated Couples in Italian Context: Communalities and
      Singularities of Women and Men Experiences.
AB  - Relationship breakdown and separation represent a critical aspect in domestic
      violence. Few studies have investigated domestic violence in separated couples.
      Moreover, there is a need for a more in depth analysis of gender differences that
      could enhance the comprehension of the phenomenon. The primary aim of this
      research was to analyze, through a qualitative approach, which kinds of domestic
      violence are characteristic or major in separated couples in the Italian context,
      where this phenomenon has not yet been sufficiently investigated. Participants
      are 60 separated couples (mean age: M = 48; F = 44) who attended a Family
      Mediation Center. A descriptive study was conducted using grounded theory
      methodology. A brief narrative task was administered to both ex-partners
      separately. The transcriptions were analyzed using NVivo 11 software. From data
      analysis, some themes emerged regarding typology of domestic violence specific of
      the separation context and shared by both men and women. The analyses of gender
      differences showed that there is a gender specific experience of domestic
      violence. Results highlight that women narrate both physical and psychological
      violence, while men relate only psychological abuse focused on limiting access to
      children. We discuss these findings in relation to possible appropriate gender
      specific intervention and prevention efforts.

PMID- 30233458
TI  - Avoidant/Restrictive Food Intake Disorder: A Longitudinal Study of Malnutrition
      and Psychopathological Risk Factors From 2 to 11 Years of Age.
AB  - Aim: To evaluate different types and degrees of malnutrition over time in a
      sample of children diagnosed with Infantile Anorexia (IA), based on the DC:0-3R
      criteria, and recently defined by DSM-5 as the first subtype of
      Avoidant/Restrictive Food Intake Disorder (ARFID), and to investigate the
      relationship between children's severity of malnutrition and emotional/behavioral
      development, and mothers' long-term psychopathological symptoms. Methods: A total
      of 113 children (58 boys, 55 girls), originally diagnosed with IA, and their
      mothers, were evaluated at four assessment points at the children's mean age of
      2, 5, 7, and 11 years. Several measures were used to assess the children's growth
      and level of malnutrition, mothers' psychopathological symptoms and eating
      attitudes, as well as their children's emotional/behavioral functioning. Results:
      A steady improvement in the severity of malnutrition over time emerged, but 73%
      of children still had ongoing mild to moderate to severe malnutrition at 11 years
      of age. Moreover, the children showed increasing internalizing and externalizing
      emotional/behavioral problems, and their mothers' psychopathological symptoms and
      eating problems worsened as well over time. At 11 years of age, the girls'
      emotional/behavioral problems and their mothers' psychopathology and disturbed
      eating attitudes were more severe than that of the boys and their mothers.
      Finally, during the last assessment, significant associations between the
      mothers' psychopathology and disturbed eating attitudes, the severity of the
      children's malnutrition, and their emotional/behavioral problems emerged.
      Discussion: Our longitudinal study points out that the developmental course of
      children, originally diagnosed with IA and who received limited psychosocial
      treatment, is characterized by an enduring risk of malnutrition and increasing
      psychopathological symptoms in both, the children and their mothers, up to the
      sensitive period of pre-puberty.

PMID- 30233459
TI  - Associations Between Perception of Parental Behavior and "Person Picking an Apple
      From a Tree" Drawings Among Children With and Without Special Educational Needs
      (SEN).
AB  - The present study examines and compares associations between perceptions of
      parental acceptance/rejection in 191 Greek school age children (84 inclusion
      class students and 107 typical class students, age range 10-12), and their
      "Person Picking an Apple from a Tree" (PPAT) drawings. Perception of parental
      behavior was measured by the "Parental Acceptance-Rejection Questionnaire"
      (Rohner and Khaleque, 2005). Drawing content was analyzed quantitatively
      according to a reliable rating system called the Symbolic Content in PPAT
      drawings (SC-PPAT: Bat Or et al., 2014, 2017). We employed k-means cluster
      analysis and obtained three relatively discrete PPAT scripts. Drawing content
      elements and scripts were found to be associated with children's perceptions of
      parental behavior; these associations were found mainly among children with
      special educational needs (SEN) and boys. Results are discussed in terms of
      children's subjective experience, clinical implications, and future research
      directions.

PMID- 30233460
TI  - Intrafamilial Phenotypic Variability in the C9orf72 Gene Expansion: 2 Case
      Studies.
AB  - The C9orf72 genetic mutation is the most common cause of familial frontotemporal
      dementia (FTD) and motor neuron disease (MND). Previous family studies suggest
      that while some common clinical features may distinguish gene carriers from
      sporadic patients, the clinical features, age of onset and disease progression
      vary considerably in affected patients. Whilst disease presentations may vary
      across families, age at disease onset appears to be relatively uniform within
      each family. Here, we report two individuals with a C9orf72 repeat expansion from
      two generations of the same family with markedly different age at disease onset,
      clinical presentation and disease progression: one who developed motor neuron and
      behavioural symptoms in their mid 40s and died 3 years later with confirmed TDP
      43 pathology and MND; and a second who developed cognitive and mild behavioural
      symptoms in their mid 70s and 8 years later remains alive with only slow
      deterioration. This report highlights the phenotypic variability, including age
      of onset, within a family with the C9orf72 repeat expansion.

PMID- 30233461
TI  - Activation vs. Experiential Avoidance as a Transdiagnostic Condition of Emotional
      Distress: An Empirical Study.
AB  - Background: From a contextual transdiagnostic approach, this study focuses on the
      importance of the processes of Experiential Avoidance and Activation in
      explaining and treating psychological problems. There exists widespread empirical
      evidence to suggest that the response pattern known as Experiential Avoidance, a
      general unwillingness to remain in contact with particular private experiences
      through the use of maladaptive avoidance strategies, acts as a functional
      dimension in various psychological problems. Activation, that is, maintaining
      contact with experiences/conditions of life and consequently with associated
      sources of reward, is a condition present in most therapeutic processes. Although
      a great deal of research has analyzed the relationship of the value of reward
      with the etiology and maintenance of psychological problems, Activation, as a
      transdiagnostic factor, has been studied less. The aim of this paper is to carry
      out an empirical study of the relationship between Activation, EA and emotional
      state and analyze the capacity of these two conditions to discriminate the
      intensity and symptomatology type in subjects with emotional distress. Methods:
      The Hospital Anxiety and Depression Scale (HADS), Environmental Reward
      Observation Scale (EROS) and Behavioral Activation for Depression Scale (BADS)
      were completed by 240 health center users. Results: Of the participants, 55%
      showed clinically relevant emotional distress. All cases of depression showed
      clinical anxiety. To discriminate between subjects without (n = 109) and with
      emotional distress (n = 131), analyses of the ROC curves and logistic regression
      analysis identified the BADS-Avoidance/Rumination followed by the EROS. To
      discriminate between subjects with anxiety but without depression (n = 61) and
      with anxiety and depression (n = 70), the most efficient scales were EROS
      followed by BADS-Social Impairment. Conclusion: It was shown that people with no
      emotional complaints maintained greater contact with life experiences and with
      environmental sources of reward than those with emotional distress. Response
      patterns showing Experiential Avoidance and a reduction in Activation responses
      were associated with clinical distress. A reduction in Activation was the
      condition which distinguished those people with the greatest distress and also
      the greatest comorbidity of symptoms of depression and anxiety. These data
      support the transdiagnostic nature of Activation and suggest greater attention
      should be paid to this concept.

PMID- 30233462
TI  - Single-Session Attention Bias Modification Training in Victims of Work-Related
      Accidents.
AB  - Individuals who experienced traumatic work-related accidents frequently show
      cognitive deficits and biased processing of trauma-relevant information, which,
      in turn, could increase the risk of further accidents. The attention bias
      modification training (ABMT) is designed to reduce hypervigilance toward and
      enhance attentional disengagement from threat stimuli. The aim of the present
      study was to assess whether it is possible to implicitly reduce the attentional
      bias toward trauma-related stimuli through a single session of ABMT in
      individuals who experienced a traumatic occupational accident. Nineteen
      individuals who had experienced a traumatic work-related accident and 11 workers
      who never experienced a work accident (control group) underwent a preliminary
      assessment of cognitive performance (executive functions and sustained attention)
      and an evaluation of the attentional bias toward accident-related pictures by
      means of a dot-probe task. The results showed that injured workers performed more
      poorly than controls in tasks of executive functions and concentration abilities.
      Also, injured workers showed an attentional bias toward trauma reminders (i.e.,
      faster reaction times to probes replacing trauma-related pictures). Injured
      workers were then randomly allocated to a single-session of ABMT (N = 10) or to
      an Attention Control Condition (ACC; N = 9). After the training, the dot-probe
      task was administered again to assess changes in the attentional bias toward
      trauma-relevant pictures. Injured workers who underwent the ABMT, but not those
      who underwent the ACC, showed a significant reduction of the attentional bias
      from pre- to post-training. Overall, these results support previous findings
      reporting an association between traumatic occupational accidents and cognitive
      dysfunctions. More importantly, these preliminary findings add to a growing body
      of evidence suggesting the effectiveness of a short ABMT in reducing the
      attentional bias after a traumatic workplace accident.

PMID- 30233463
TI  - The Influence of Face Inversion and Spatial Frequency on the Self-Positive
      Expression Processing Advantage.
AB  - Previous research has examined the impact of late self-evaluation, ignoring the
      impact of the early visual coding stage and the extraction of facial identity
      information and expression information on the self-positive expression processing
      advantage. From the perspective of the processing course, this study examined the
      stability of the self-positive expression processing advantage and revealed its
      generation mechanism. In Experiment 1, inverted self-expression and others'
      expressive pictures were used to influence early structural coding. In
      Experiments 2a and 2b, we used expression pictures of high and low spatial
      frequency, thereby affecting the extraction of facial identity information or
      expression information in the mid-term stage. The visual search paradigm was
      adopted in three experiments, asking subjects to respond to the target
      expression. We found that under the above experimental conditions, the search
      speed for self-faces was always faster than that for self-angry expressions and
      others' faces. These results showed that, compared with others' expressions and
      self-angry expressions, self-positive expressions were more prominent and more
      attractive. These findings suggest that self-expression recognition combines with
      conceptual self-knowledge to form an abstract and constant processing pattern.
      Therefore, the processing of self-expression recognition was not affected by the
      facial orientation and spatial frequencies.

PMID- 30233464
TI  - Therapy Dogs as a Crisis Intervention After Traumatic Events? - An Experimental
      Study.
AB  - Animal-assisted therapy has been proposed as a treatment adjunct for traumatized
      patients. In animal-assisted crisis response, dogs are used directly after a
      traumatic event to reduce stress and anxiety. However, to date there are few
      controlled studies investigating the effects of therapy dogs on PTSD symptoms and
      to our knowledge there is no study investigating the effects of a therapy dog
      intervention directly after a traumatic event. In this study, 60 healthy female
      participants were randomly assigned to one of three groups: after exposure to a
      "traumatic" film clip (trauma-film paradigm), one group of participants
      interacted with a friendly dog for 15 min, another group of participants watched
      a film clip showing a person interacting with a friendly dog and the last group
      was instructed to relax. Participants who had interacted with the dog after the
      film reported lower anxiety levels, less negative affect, and more positive
      affect after the intervention as compared to the other two groups. However, the
      participants who interacted with the dog showed a smaller decrease in
      physiological arousal after the traumatic film clip compared to both other
      groups. There were no differences in intrusion symptoms between the three groups.
      Our results show that dogs are able to lessen subjectively experienced stress and
      anxiety after a "traumatic" stress situation.

PMID- 30233465
TI  - Empathy and the Public Perception of Stillbirth and Memory Sharing: An Australian
      Case.
AB  - Objective: Stillbirth devastates families and leaves them struggling to grieve
      the death of their baby in a society that expects grief symptoms to decrease over
      time. Previous research has suggested that increased memory sharing opportunities
      can lead to positive mental health outcomes. The aim of the current study was to
      examine people's perceptions of stillbirth as well as the perceived
      appropriateness of affected parents sharing memories of their child. In addition,
      we examined whether manipulating empathy would have an effect on people's
      perceptions of stillbirth. Method: Participants included 200 Australian men and
      women 18 to 74 years of age (M = 36.76, SD = 12.59) randomly allocated to one of
      three experimental conditions (i.e., low empathy, high empathy, and control). The
      high empathy group watched a video about stillbirth and was instructed to imagine
      how the people portrayed felt; the low empathy group watched the same video but
      was instructed to remain detached; and the control group watched an unrelated
      video. Participants were then asked how much money they would be willing to
      donate to a fictional stillbirth organization, followed by the completion of
      questionnaires measuring (a) perceptions of stillbirth, (b) empathy, and (c) the
      appropriateness of parents sharing memories of a stillborn child with different
      groups of people over time. Results: The empathy manipulation had an effect on
      empathy and the willingness to help effected parents (high empathy vs. control).
      However, empathy did not have an effect on participants' perceptions toward
      stillbirth nor appropriateness of sharing memories. The appropriateness of
      sharing memories decreased as time passed and social distance increased.
      Discussion: Individuals who have experienced stillbirth need to be aware that
      societal expectations and their own expectations in relation to sharing memories
      may not correspond to each other and that they may need to educate their social
      group about their need to share memories. Removing the taboo surrounding
      stillbirth is vital for both parents and those to whom they would wish to
      communicate.

PMID- 30233466
TI  - Processing Information During Regressions: An Application of the Reverse Boundary
      Change Paradigm.
AB  - Although 10-15% of eye-movements during reading are regressions, we still know
      little about the information that is processed during regressive episodes. Here,
      we report an eye-movement study that uses what we call the reverse boundary
      change technique to examine the processing of lexical-semantic information during
      regressions, and to establish the role of this information during recovery from
      processing difficulty. In the critical condition of the experiment, an initially
      implausible sentence (e.g., There was an old house that John had ridden when he
      was a boy) was rendered plausible by changing a context word (house) to a lexical
      neighbor (horse) using a gaze-contingent display change, at the point where the
      reader's gaze crossed an invisible boundary further on in the sentence. Due to
      the initial implausibility of the sentence, readers often launched regressions
      from the later part of the sentence. However, despite this initial processing
      difficulty, reading was facilitated, relative to a condition where the display
      change did not occur (i.e., the word house remained on screen throughout the
      trial). This result implies that the relevant lexical semantic information was
      processed during the regression, and was used to aid recovery from the initial
      processing difficulty.

PMID- 30233467
TI  - Older Adults Experiences of Learning to Use Tablet Computers: A Mixed Methods
      Study.
AB  - Background: We wanted to understand older adults' experiences of learning how to
      use a tablet computer in the context of an intervention trial, including what
      they found helpful or unhelpful about the tablet training, to guide future
      intervention studies. Methods: Mixed methods study using questionnaire and focus
      group approaches. Forty-three participants aged between 65 and 76 years old from
      the "Tablet for Healthy Ageing" study (comprising 22 in the intervention group
      and 21 controls) completed a post-intervention tablet experience questionnaire.
      Those who completed the tablet training intervention were invited to share their
      experiences of engaging with new technology in post-intervention focus groups. We
      conducted three separate focus groups with 14 healthy older adults (10 females).
      Results: Questionnaire data suggested that the overall experience of the 22
      participants who participated in the tablet training intervention was positive.
      The majority of participants said that it was likely or very likely they would
      use a tablet in the future. The focus group themes that emerged were related to
      the perception of tablet training, the experience of using tablets, and
      suggestions for future studies. Participants mentioned that their confidence was
      increased, that they enjoyed being part of a social group and downloading
      applications, but they also felt challenged at times. Advantages of using tablets
      included the ability to keep in touch with family and friends, a motivation to
      contribute to the community, and the potential for tablets to improve mental
      abilities and overall health and wellbeing. Participants made suggestions that
      would enable tablet usage, including improvement of features, and suggestions
      that would improve future tablet training studies, including smaller classes.
      Conclusion: Our findings have implications for the development of interventions
      utilizing new technologies that might promote the health and wellbeing of older
      adults.

PMID- 30233468
TI  - Trait Emotional Intelligence Profiles of Parents With Drug Addiction and of Their
      Offspring.
AB  - This study examines the relationship between trait emotional intelligence (trait
      EI) and general health (General Health; GHQ-28) in two samples of Greek parents
      with (n = 52; Mage = 39.78; SDage = 6.68; 41 men and 11 women) and without (n =
      51; Mage = 43.53; SDage = 4.61; 40 men and 11 women) addiction problems. In
      addition, it compares the trait EI scores of their offspring (N = 81; Mage =
      11.71; SDage = 2.15; 51 boys and 30 girls). Results showed that parents with drug
      addiction exhibited lower levels of trait EI and poorer general health than
      peers. In addition, global trait EI and two of its subscales, Well-being and
      Emotionality, had stronger correlations with depression in the addiction than in
      the comparison group. Well-being was a significant predictor of general health
      and its subscales (Somatic symptoms, Anxiety/insomnia, Social dysfunction, and
      severe depression) in both groups. No differences were found between the
      offspring of the two groups.

PMID- 30233469
TI  - Is Social Support a Cause or Consequence of Depression? A Longitudinal Study of
      Adolescents.
AB  - A large body of literature has examined the relations between social support and
      depression. However, the exact nature and direction of these relations are not
      well understood. This study explored the relations between specific types of
      social support (peer support and teacher support) and depression. Adolescents
      (ages 11 to 17) for the first time (N = 2453) participated in a two-wave, 6-month
      longitudinal study. Structural equation modeling was used to test a social
      causation model (deficits in social support increase the likelihood of
      depression), interpersonal theories of depression (depression leads to social
      erosion), and a reciprocal influence model. Depression influenced peer support
      significantly and negatively. By contrast, the social causation model was not
      supported. These results held for males and females. Findings suggested that
      depression resulted in social support erosion. However, the effect was specific
      to perceived peer support but not to perceived teacher support.

PMID- 30233470
TI  - The Contribution of Attention to the Mere Exposure Effect for Parts of
      Advertising Images.
AB  - Repeatedly presented stimuli are affectively evaluated more positively than novel
      stimuli. This phenomenon, known as the mere exposure effect, is used in
      advertising. However, it is still unclear in which part of advertising images the
      mere exposure effect occurs. Given the recent suggestion that attention plays an
      important role in the mere exposure effect, it is possible that the mere exposure
      effect does not occur for commercial products when advertising images consist of
      a commercial product along with an attractive human model. To investigate this
      possibility, we manipulated the relationship between advertising images
      repeatedly presented in an exposure phase and images presented in a later rating
      phase. In the exposure phase, participants were repeatedly presented with
      advertising images consisting of a cosmetic product along with an attractive
      female model and were instructed to attend to a specified part of the image
      (Experiment 4) or were given no such an instruction (Experiments 1, 2, and 3). In
      the rating phase, participants were asked to evaluate their preference for
      complete advertising images (Experiment 1), the images of female models
      (Experiment 2), or images of products (Experiments 3 and 4) that were previously
      presented or not presented. The mere exposure effect was found for whole
      advertising images and images of female models. On the other hand, the mere
      exposure effect for the images of products was seen only when participants were
      explicitly encouraged to direct their attention to the product parts of the
      advertising image. That is, the results of this study suggest that the mere
      exposure effect does not always occur for every part of the repeated advertising
      images, and that attention would modulate the mere exposure effect for
      advertising images.

PMID- 30233471
TI  - Corrigendum: Centeredness Theory: Understanding and Measuring Well-Being Across
      Core Life Domains.
AB  - [This corrects the article DOI: 10.3389/fpsyg.2018.00610.].

PMID- 30233472
TI  - Periodization and Self-Regulation in Action Sports: Coping With the Emotional
      Load.
AB  - Action sports usually include some danger and personal challenge. The levels of
      both are often further increased when the sport is placed in a competitive
      environment. In this paper, we consider the Olympic disciplines of freeskiing and
      snowboarding in park and pipe. We consider some pertinent theoretical
      perspectives, then offer some insights on their operation using a range of data
      from ongoing research and support work. Finally, we offer a number of practical
      steps which can be taken to optimize performance, both in learning and practicing
      new tricks and in executing them under the pressures of competition.

PMID- 30233473
TI  - White-Matter Structural Connectivity in Relation to Humor Styles: An Exploratory
      Study.
AB  - To investigate the potential relationship between white matter (WM)
      microstructure and humor styles, diffusion tensor images of brain WM and humor
      style tendencies were obtained from thirty healthy adults. Using connectivity
      efficiency measures from graph theoretical analysis and controlling for the
      influence of gender, age, educational level, and the big five personality traits,
      we preliminarily examined the prediction of humor styles from brain network
      efficiency. The results showed that the local efficiency within particular brain
      networks positively predicted a self-enhancing humor style and negatively
      predicted an aggressive humor style. The node efficiency of the left superior
      temporal gyrus distinguished the benevolent or hostile way that individuals coped
      with interpersonal embarrassment. These findings from this exploratory study
      support the hypothesis that WM structure influences humor styles, and provide the
      initial evidence and implications regarding the relationship between biological
      mechanisms and mental health for future research.

PMID- 30233474
TI  - "I" and "Me": The Self in the Context of Consciousness.
AB  - James (1890) distinguished two understandings of the self, the self as "Me" and
      the self as "I". This distinction has recently regained popularity in cognitive
      science, especially in the context of experimental studies on the underpinnings
      of the phenomenal self. The goal of this paper is to take a step back from
      cognitive science and attempt to precisely distinguish between "Me" and "I" in
      the context of consciousness. This distinction was originally based on the idea
      that the former ("Me") corresponds to the self as an object of experience (self
      as object), while the latter ("I") reflects the self as a subject of experience
      (self as subject). I will argue that in most of the cases (arguably all) this
      distinction maps onto the distinction between the phenomenal self (reflecting
      self-related content of consciousness) and the metaphysical self (representing
      the problem of subjectivity of all conscious experience), and as such these two
      issues should be investigated separately using fundamentally different
      methodologies. Moreover, by referring to Metzinger's (2018) theory of phenomenal
      self-models, I will argue that what is usually investigated as the phenomenal-"I"
      [following understanding of self-as-subject introduced by Wittgenstein (1958)]
      can be interpreted as object, rather than subject of experience, and as such can
      be understood as an element of the hierarchical structure of the phenomenal self
      model. This understanding relates to recent predictive coding and free energy
      theories of the self and bodily self discussed in cognitive neuroscience and
      philosophy.

PMID- 30233475
TI  - Temporarily Out of Order: Temporal Perspective Taking in Language in Children
      With Autism Spectrum Disorder.
AB  - Clinical reports suggest that children with autism spectrum disorder (ASD)
      struggle with time perception, but few studies have investigated this. This is
      the first study to examine these children's understanding of before and after.
      These temporal conjunctions have been argued to require additional cognitive
      effort when conjoining two events in a clause order that is incongruent with
      their order in time. Given the suggested time perception impairment and well
      established cognitive deficits of children with ASD, we expected them to have
      difficulties interpreting temporal conjunctions, especially in an incongruent
      order. To investigate this, the interpretation of before and after in congruent
      and incongruent orders was examined in 48 children with ASD and 43 typically
      developing (TD) children (age 6-12). Additional tasks were administered to
      measure Theory of Mind (ToM), working memory (WM), cognitive inhibition,
      cognitive flexibility, IQ, and verbal ability. We found that children with ASD
      were less accurate in their interpretation of temporal conjunctions than their TD
      peers. Contrary to our expectations, they did not have particular difficulties in
      an incongruent order. Furthermore, older children showed better overall
      performance than younger children. The difference between children with ASD and
      TD children was explained by WM, ToM, IQ, and verbal ability, but not by
      cognitive inhibition and flexibility. These cognitive functions are more likely
      to be impaired in children with ASD than in TD children, which could account for
      their poorer performance. Thus, the cognitive factors found to affect the
      interpretation of temporal language in children with ASD are likely to apply in
      typical development as well. Sufficient WM capacity and verbal ability may help
      children to process complex sentences conjoined by a temporal conjunction.
      Additionally, ToM understanding was found to be related to children's
      interpretation of temporal conjunctions in an incongruent order, indicating that
      perspective taking is required when events are presented out of order. We
      conclude from this that perspective-taking abilities are needed for the
      interpretation of temporal conjunctions, either to shift one's own perspective as
      a hearer to another point in time, or to shift to the perspective of the speaker
      to consider the speaker's linguistic choices.

PMID- 30233476
TI  - Psychotherapy in Psychosis: Experiences of Fully Recovered Service Users.
AB  - Background: Despite the evidence of the importance of including service users'
      views on psychotherapy after psychosis, there is a paucity of research
      investigating impact on full recovery. Objectives: To explore what fully
      recovered service users found to be the working ingredients of psychotherapy in
      the recovery process after psychosis. Materials and Methods: The study was
      designed as a phenomenological investigation with thematic analysis as the
      practical tool for analysis. Twenty fully recovered service users were
      interviewed. Results: Themes: (1) Help with the basics, (2) Having a companion
      when moving through chaotic turf, (3) Creating a common language, (4) Putting
      psychosis in brackets and cultivate all that is healthy, and (5) Building a
      bridge from the psychotic state to the outside world. Conclusion: Therapeutic
      approaches sensitive to stage specific functional challenges seemed crucial for
      counteracting social isolation and achieving full recovery. Findings indicate
      that psychotherapy focusing on early readjustment to everyday activities, to what
      are perceived as meaningful and recovery-oriented, seems to be what is preferred
      and called for by service users.

PMID- 30233477
TI  - Flow and Immersion in Video Games: The Aftermath of a Conceptual Challenge.
AB  - One of the most pleasurable aspects of video games is their ability to induce
      immersive experiences. However, there appears to be a tentative conceptualization
      of what an immersive experience is. In this short review, we specifically focus
      on the terms of flow and immersion, as they are the most widely used and applied
      definitions in the video game literature, whilst their differences remain
      disputable. We critically review the concepts separately and proceed with a
      comparison on their proposed differences. We conclude that immersion and flow do
      not substantially differ in current studies and that more evidence is needed to
      justify their separation.

PMID- 30233478
TI  - Impulse Control Disorder in Parkinson's Disease: A Meta-Analysis of Cognitive,
      Affective, and Motivational Correlates.
AB  - Background: In Parkinson's disease (PD), impulse control disorders (ICDs) develop
      as side-effect of dopaminergic replacement therapy (DRT). Cognitive, affective,
      and motivational correlates of ICD in medicated PD patients are debated. Here, we
      systematically reviewed and meta-analyzed the evidence for an association between
      ICD in PD and cognitive, affective, and motivational abnormalities. Methods: A
      systematic review and meta-analysis was performed on PubMed, Science Direct, ISI
      Web of Science, Cochrane, EBSCO for studies published between 1-1-2000 and 8-3
      2017 comparing cognitive, affective, and motivational measures in PD patients
      with ICD (ICD+) vs. those without ICD (ICD-). Exclusion criteria were conditions
      other than PD, substance and/or alcohol abuse, dementia, drug naive patients,
      cognition assessed by self-report tools. Standardized mean difference (SMD) was
      used, and random-effect model applied. Results: 10,200 studies were screened
      (title, abstract), 79 full-texts were assessed, and 25 were included (ICD+: 625
      patients; ICD-: 938). Compared to ICD-, ICD+ showed worse performance reward
      related decision-making (0.42 [0.02, 0.82], p = 0.04) and set-shifting tasks (SMD
      = -0.49 [95% CI -0.78, -0.21], p = 0.0008). ICD in PD was also related to higher
      self-reported rate of depression (0.35 [0.16, 0.54], p = 0.0004), anxiety (0.43
      [0.18, 0.68], p = 0.0007), anhedonia (0.26 [0.01, 0.50], p = 0.04), and
      impulsivity (0.79 [0.50, 1.09], p < 0.00001). Heterogeneity was low to moderate,
      except for depression (I2 = 61%) and anxiety (I2 = 58%). Conclusions: ICD in PD
      is associated with worse set-shifting and reward-related decision-making, and
      increased depression, anxiety, anhedonia, and impulsivity. This is an important
      area for further studies as ICDs have negative impact on the quality of life of
      patients and their caregivers.

PMID- 30233479
TI  - Hypertension and High Blood Pressure Are Associated With Dementia Among Chinese
      Dwelling Elderly: The Shanghai Aging Study.
AB  - Background: To explore the association between blood pressure and cognition in
      older participants in the Shanghai Aging Study. Methods: Data were drawn from
      3,327 participants at the baseline of Shanghai Aging Study. History of
      hypertension was inquired and confirmed from participants' medical records.
      Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by
      research nurses in the early morning. Participants were diagnosed with "cognitive
      normal," "mild cognitive impairment (MCI)," or "dementia" by neurologists using
      DSM-IV and Petersen criteria. Multivariate logistic regression was used to
      evaluate the association between history of hypertension, duration of
      hypertension, SBP, DBP, or classification of blood pressure and cognitive
      function. Generalized linear model was used to assess the relation between
      duration of hypertension, SBP, or DBP and Mini Mental State Examination (MMSE).
      Results: A significantly higher proportion of hypertension [78 (76.5%)] was found
      in participants with dementia than in those with MCI [347 (59.3%)] and cognitive
      normal [1,350 (51.1%)] (P < 0.0001). Participants with dementia had significantly
      higher SBP [157.6 (26.1) mmHg] than those with MCI [149.0 (23.7) mmHg] and
      cognitive normal [143.7 (22.6) mmHg] (P < 0.0001). After adjusting for sex, age,
      education, living alone, body mass index, anxiety, depression, heart disease,
      diabetes, and stroke, the likelihood of having dementia was positively associated
      with history of hypertension (OR = 2.10; 95% CI: 1.22, 3.61), duration of
      hypertension (OR = 1.02 per increment year; 95% CI: 1.01, 1.04), higher SBP (OR =
      1.14 per increment of 10 mmHg; 95% CI: 1.04, 1.25), higher DBP (OR = 1.22 per
      increment of 10 mmHg; 95% CI: 1.02, 1.45), moderate hypertension (OR = 2.09; 95%
      CI: 1.10, 3.99), or severe hypertension (OR = 2.45; 95% CI: 1.20, 4.99). The MMSE
      score was inversely correlated to duration of hypertension (beta = -0.0088 per
      increment year; 95% CI: -0.0158, -0.0018, P = 0.0132), SBP (beta = -0.0655 per
      increment of 10 mmHg; 95% CI: -0.1022, -0.0288, P = 0.0005), and DBP (beta = 
      0.1230 per increment of 10 mmHg; 95% CI: -0.1915, -0.0545, P = 0.0004).
      Conclusion: Our results suggest that hypertension and high blood pressure may be
      potential risk factors for dementia. Blood pressure management for the elderly
      may be important for maintaining cognitive vitality.

PMID- 30233481
TI  - Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune
      Encephalitis.
AB  - In recent years, new antibodies have been discovered which mediate autoimmune
      encephalitis. This immunological response can be triggered by an infection or a
      tumor. Classical onconeuronal antibodies are directed against intracellular
      neuronal agents but recently, a novel group of antibodies to neuronal cell
      surface and synaptic antigens associated with different CNS-syndromes, has been
      discovered. Interestingly, the syndromes in this group can be successfully
      treated with immunotherapy and frequently do not have underlying tumors. The aim
      of this review is to describe the current state of knowledge about autoimmune
      encephalitis, in order to provide clinicians with a concise, up-to-date overview.
      Thus, a comprehensive literature search was performed in medical databases. The
      literature was carefully studied and new findings focusing on the symptoms,
      diagnosis and treatment were summarized and interpreted. Even though it might be
      challenging in some cases, the awareness of certain symptom constellations and
      demographic information, in combination with laboratory- and MRI-results, allows
      clinicians to make the diagnosis of probable autoimmune encephalitis at an early
      stage. Treatment can therefore be initiated faster, which significantly improves
      the outcome. Further investigations could define the underlying pathogenic
      mechanisms. Randomized controlled trials, paired with increasing clinical
      experience, will be necessary to improve the identification of affected patients,
      treatment strategies, and outcomes in the years to come.

PMID- 30233480
TI  - Conscious While Being Considered in an Unresponsive Wakefulness Syndrome for 20
      Years.
AB  - Despite recent advances in our understanding of consciousness disorders, accurate
      diagnosis of severely brain-damaged patients is still a major clinical challenge.
      We here present the case of a patient who was considered in an unresponsive
      wakefulness syndrome/vegetative state for 20 years. Repeated standardized
      behavioral examinations combined to neuroimaging assessments allowed us to show
      that this patient was in fact fully conscious and was able to functionally
      communicate. We thus revised the diagnosis into an incomplete locked-in syndrome,
      notably because the main brain lesion was located in the brainstem. Clinical
      examinations of severe brain injured patients suffering from serious motor
      impairment should systematically include repeated standardized behavioral
      assessments and, when possible, neuroimaging evaluations encompassing magnetic
      resonance imaging and 18F-fluorodeoxyglucose positron emission tomography.

PMID- 30233482
TI  - A Machine Learning Approach to Perfusion Imaging With Dynamic Susceptibility
      Contrast MR.
AB  - Background: Dynamic susceptibility contrast (DSC) MR perfusion is a frequently
      used technique for neurovascular imaging. The progress of a bolus of contrast
      agent through the tissue of the brain is imaged via a series of T2*-weighted MRI
      scans. Clinically relevant parameters such as blood flow and Tmax can be
      calculated by deconvolving the contrast-time curves with the bolus shape
      (arterial input function). In acute stroke, for instance, these parameters may
      help distinguish between the likely salvageable tissue and irreversibly damaged
      infarct core. Deconvolution typically relies on singular value decomposition
      (SVD): however, studies have shown that these algorithms are very sensitive to
      noise and artifacts present in the image and therefore may introduce distortions
      that influence the estimated output parameters. Methods: In this work, we present
      a machine learning approach to the estimation of perfusion parameters in DSC-MRI.
      Various machine learning models using as input the raw MR source data were
      trained to reproduce the output of an FDA approved commercial implementation of
      the SVD deconvolution algorithm. Experiments were conducted to determine the
      effect of training set size, optimal patch size, and the effect of using
      different machine-learning models for regression. Results: Model performance
      increased with training set size, but after 5,000 samples (voxels) this effect
      was minimal. Models inferring perfusion maps from a 5 by 5 voxel patch
      outperformed models able to use the information in a single voxel, but larger
      patches led to worse performance. Random Forest models produced had the lowest
      root mean squared error, with neural networks performing second best: however, a
      phantom study revealed that the random forest was highly susceptible to noise
      levels, while the neural network was more robust. Conclusion: The machine
      learning-based approach produces estimates of the perfusion parameters invariant
      to the noise and artifacts that commonly occur as part of MR acquisition. As a
      result, better robustness to noise is obtained, when evaluated against the FDA
      approved software on acute stroke patients and simulated phantom data.

PMID- 30233483
TI  - Proton Magnetic Resonance Spectroscopy Biomarkers in Neonates With Hypoxic
      Ischemic Encephalopathy: A Systematic Review and Meta-Analysis.
AB  - Background: Hypoxic-ischemic encephalopathy (HIE) is a major contributor to child
      mortality and morbidity. Reliable prognostication for HIE is of key importance.
      Proton magnetic resonance spectroscopy (1H-MRS) is a quantitative, non-invasive
      method that has been demonstrated to be a suitable complementary tool for
      prediction. The aim of this study was to investigate the prognostic capability of
      1H-MRS in the era of therapeutic hypothermia (TH). Methods: Databases, namely
      MEDLINE, Embase, Web of Science, and the Cochrane library (Cochrane Center
      Register of Controlled Trials), were searched for studies published before July
      17, 2017. Study selection and data extraction were performed by two independent
      reviewers. The mean difference (MD) or standardized MD (SMD) and 95% confidence
      interval (CI) were calculated using random-effects models. Subgroup analyses were
      conducted based on the use of TH. Results: Among the 1,150 relevant studies,
      seven were included for meta-analysis, but only two small studies were conducted
      under TH. For 1H-MRS measurement, three peak area ratios revealed predictive
      values for adverse outcomes in TH subgroup and the combined results (with and
      without TH): N-acetylaspartate (NAA)/creatine in basal ganglia/thalamus (BG/T) in
      TH (MD -0.31, 95%CI -0.55 to -0.07) and combined results (MD -0.37, 95% CI -0.49
      to -0.25); NAA/choline in BG/T in TH (MD -0.89, 95%CI -1.43 to -0.35) and
      combined results (MD -0.25, 95%CI -0.42 to -0.07); and myo-inositol/choline in
      cerebral cortex in TH (MD -1.94, 95%CI -3.69 to -0.19) and combined results (MD 
      1.64, 95%CI -2.64 to -0.64). Moreover, NAA relative concentration is associated
      with adverse outcomes: in TH (MD -0.04, 95%CI -0.06 to -0.02) and combined
      results (MD -0.06, 95%CI -0.11 to -0.01) in white matter; in TH (MD -0.04, 95%CI 
      0.07 to -0.01) and combined results (MD -0.05, 95%CI -0.07 to -0.02) in gray
      matter. Conclusions: NAA may be a potential marker in outcome prediction for all
      HIE subjects. It seems that MDs for the ratios including NAA are larger than for
      its relative concentration, and therefore are more likely to be measurable in a
      clinical context. Larger prospective multicenter studies with a standardized
      protocol for both measurement protocols and analysis methods are required in
      future studies.

PMID- 30233485
TI  - Hippocampal Functional Dynamics Are Clinically Implicated in Autoimmune
      Encephalitis With Faciobrachial Dystonic Seizures.
AB  - This is the first study to investigate functional brain activity in patients
      affected by autoimmune encephalitis with faciobrancial dystonic seizures (FBDS).
      Multimodal 3T MRI scans, including structural neuroimaging (T1-weighted,
      diffusion weighted) and functional neuroimaging (scene-encoding task known to
      activate hippocampal regions), were performed. This case series analysis included
      eight patients treated for autoimmune encephalitis with FBDS, scanned during the
      convalescent phase of their condition (median 1.1 years post-onset), and eight
      healthy volunteers. Compared to controls, 50% of patients showed abnormal
      hippocampal activity during scene-encoding relative to familiar scene-viewing.
      Higher peak FBDS frequency was significantly related to lower hippocampal
      activity during scene-encoding (p = 0.02), though not to markers of hippocampal
      microstructure (mean diffusivity, p = 0.3) or atrophy (normalized volume, p =
      0.4). During scene-encoding, stronger within-medial temporal lobe (MTL)
      functional connectivity correlated with poorer Addenbrooke's Cognitive
      Examination-Revised memory score (p = 0.03). These findings suggest that in
      autoimmune encephalitis, frequent seizures may have a long-term impact on
      hippocampal activity, beyond that of structural damage. These observations also
      suggest a potential approach to determine on-going MTL performance in this
      condition to guide long-term management and future clinical trials.

PMID- 30233486
TI  - Sporadic MM-1 Type Creutzfeldt-Jakob Disease With Hemiballic Presentation and No
      Cognitive Impairment Until Death: How New NCJDRSU Diagnostic Criteria May Allow
      Early Diagnosis.
AB  - Sporadic Creutzfeldt-Jakob disease is the most common human prion disorder.
      Although associated with heterogeneous clinical phenotypes, its distinctive
      feature is the presence of a rapidly progressive multidomain cognitive
      impairment. We describe the atypical case of a patient affected by sporadic
      Methionine/Methionine type 1 Creutzfeldt-Jakob disease (typically associated with
      early cognitive decline) who presented with an isolated hemiballic syndrome and
      no signs of cognitive involvement until death. We review sporadic Creutzfeldt
      Jakob disease diagnostic criteria and their updates since their first
      formulation, highlighting their limitations in clinical diagnostic work-up.
      Finally, we discuss the recently introduced National Creutzfeldt-Jakob Disease
      Research and Surveillance Unit diagnostic criteria, suggesting how their
      application could support an early clinical diagnosis, even in atypical cases,
      such as the one presented.

PMID- 30233487
TI  - Identifying and Quantifying Neurological Disability via Smartphone.
AB  - Embedded sensors of the smartphones offer opportunities for granular, patient
      autonomous measurements of neurological dysfunctions for disease identification,
      management, and for drug development. We hypothesized that aggregating data from
      two simple smartphone tests of fine finger movements with differing contribution
      of specific neurological domains (i.e., strength & cerebellar functions, vision,
      and reaction time) will allow establishment of secondary outcomes that reflect
      domain-specific deficit. This hypothesis was tested by assessing correlations of
      smartphone-derived outcomes with relevant parts of neurological examination in
      multiple sclerosis (MS) patients. We developed MS test suite on Android platform,
      consisting of several simple functional tests. This paper compares cross
      sectional and longitudinal performance of Finger tapping and Balloon popping
      tests by 76 MS patients and 19 healthy volunteers (HV). The primary outcomes of
      smartphone tests, the average number of taps (per two 10-s intervals) and the
      average number of pops (per two 26-s intervals) differentiated MS from HV with
      similar power to traditional, investigator-administered test of fine finger
      movements, 9-hole peg test (9HPT). Additionally, the secondary outcomes
      identified patients with predominant cerebellar dysfunction, motor fatigue and
      poor eye-hand coordination and/or reaction time, as evidenced by significant
      correlations between these derived outcomes and relevant parts of neurological
      examination. The intra-individual variance in longitudinal sampling was low. In
      the time necessary for performing 9HPT, smartphone tests provide much richer and
      reliable measurements of several distinct neurological functions. These data
      suggest that combing more creatively-construed smartphone apps may one day
      recreate the entire neurological examination.

PMID- 30233488
TI  - Assessment of Bone Metabolism in Male Patients With Benign Paroxysmal Positional
      Vertigo.
AB  - Objective: Several studies have suggested a probable association between benign
      paroxysmal positional vertigo (BPPV) and both reduction of bone mineral density
      (BMD) and serum vitamin D levels, but none of these studies have explored their
      findings by examining bone turnover markers (BTM) in male idiopathic BPPV
      patients. This study aimed to evaluate the relationship between BMD and serum 25
      hydroxyvitamin D (25(OH) D), with the occurrence of BPPV along with the
      characteristics of bone metabolism in male idiopathic BPPV patients. Methods:
      This retrospective study comprised 60 male idiopathic BPPV patients and 92 age
      matched healthy controls referred to Ningbo No.2 Hospital during the period of
      February 2016 to February 2018. All subjects' serum levels of 25(OH) D, bone
      formation marker amino-terminal propeptide of type I procollagen (PINP), and bone
      resorption marker beta-isomerized carboxy-terminal telopeptide of type I collagen
      (beta-CTX) were measured. BMD was determined by dual energy X-ray absorption at
      the lumbar spine and hip. Results: Among male patients with BPPV, the prevalence
      of BMD reduction was 35.0%, which was similar to that of 27.2% in healthy
      controls. There were significant differences in the mean serum 25(OH) D level and
      prevalence of vitamin D deficiency between the two groups, with p-values of 0.049
      and 0.009, respectively. The bone turnover markers of PINP and beta-CTX in BPPV
      patients were lower than those in healthy controls. Logistic regression showed
      that vitamin D deficiency were associated with BPPV with an odds ratio of 3.8
      (95% confidence interval = 1.25-11.73). Conclusion: Our study found that
      decreased serum vitamin D may be a risk factor for BPPV in male patients. The
      level of bone turnover among male patients with BPPV was lower than that among
      healthy controls.

PMID- 30233484
TI  - Regenerative Medicine Therapies for Targeting Neuroinflammation After Stroke.
AB  - Inflammation is a major pathological event following ischemic stroke that
      contributes to secondary brain tissue damage leading to poor functional recovery.
      Following the initial ischemic insult, post-stroke inflammatory damage is driven
      by initiation of a central and peripheral innate immune response and disruption
      of the blood-brain barrier (BBB), both of which are triggered by the release of
      pro-inflammatory cytokines and infiltration of circulating immune cells. Stroke
      therapies are limited to early cerebral blood flow reperfusion, and whilst
      current strategies aim at targeting neurodegeneration and/or neuroinflammation,
      innovative research in the field of regenerative medicine aims at developing
      effective treatments that target both the acute and chronic phase of
      inflammation. Anti-inflammatory regenerative strategies include the use of
      nanoparticles and hydrogels, proposed as therapeutic agents and as a delivery
      vehicle for encapsulated therapeutic biological factors, anti-inflammatory drugs,
      stem cells, and gene therapies. Biomaterial strategies-through nanoparticles and
      hydrogels-enable the administration of treatments that can more effectively cross
      the BBB when injected systemically, can be injected directly into the brain, and
      can be 3D-bioprinted to create bespoke implants within the site of ischemic
      injury. In this review, these emerging regenerative and anti-inflammatory
      approaches will be discussed in relation to ischemic stroke, with a perspective
      on the future of stroke therapies.

PMID- 30233489
TI  - Regenerative Medicine and Diabetes: Targeting the Extracellular Matrix Beyond the
      Stem Cell Approach and Encapsulation Technology.
AB  - According to the Juvenile Diabetes Research Foundation (JDRF), almost 1. 25
      million people in the United States (US) have type 1 diabetes, which makes them
      dependent on insulin injections. Nationwide, type 2 diabetes rates have nearly
      doubled in the past 20 years resulting in more than 29 million American adults
      with diabetes and another 86 million in a pre-diabetic state. The International
      Diabetes Ferderation (IDF) has estimated that there will be almost 650 million
      adult diabetic patients worldwide at the end of the next 20 years (excluding
      patients over the age of 80). At this time, pancreas transplantation is the only
      available cure for selected patients, but it is offered only to a small
      percentage of them due to organ shortage and the risks linked to
      immunosuppressive regimes. Currently, exogenous insulin therapy is still
      considered to be the gold standard when managing diabetes, though stem cell
      biology is recognized as one of the most promising strategies for restoring
      endocrine pancreatic function. However, many issues remain to be solved, and
      there are currently no recognized treatments for diabetes based on stem cells. In
      addition to stem cell resesarch, several beta-cell substitutive therapies have
      been explored in the recent era, including the use of acellular extracellular
      matrix scaffolding as a template for cellular seeding, thus providing an empty
      template to be repopulated with beta-cells. Although this bioengineering approach
      still has to overcome important hurdles in regards to clinical application
      (including the origin of insulin producing cells as well as immune-related
      limitations), it could theoretically provide an inexhaustible source of bio
      engineered pancreases.

PMID- 30233491
TI  - Global Disruption of alpha2A Adrenoceptor Barely Affects Bone Tissue but
      Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone.
AB  - Evidence shows that sympathetic nervous system (SNS) activation inhibits bone
      formation and activates bone resorption leading to bone loss. Because thyroid
      hormone (TH) interacts with the SNS to control several physiological processes,
      we raised the hypothesis that this interaction also controls bone remodeling. We
      have previously shown that mice with double-gene inactivation of alpha2A- and 
      adrenoceptors (alpha2A/2C-AR-/-) present high bone mass (HBM) phenotype and
      resistance to thyrotoxicosis-induced osteopenia, which supports a TH-SNS
      interaction to control bone mass and suggests that it involves alpha2-AR
      signaling. Accordingly, we detected expression of alpha2A-AR, alpha2B-AR and
      alpha2C-AR in the skeleton, and that triiodothyronine (T3) modulates alpha2C-AR
      mRNA expression in the bone. Later, we found that mice with single-gene
      inactivation of alpha2C-AR (alpha2C-AR-/-) present low bone mass in the femur and
      HBM in the vertebra, but that both skeletal sites are resistant to TH-induce
      osteopenia, showing that the SNS actions occur in a skeletal site-dependent
      manner, and that thyrotoxicosis depends on alpha2C-AR signaling to promote bone
      loss. To further dissect the specific roles of alpha2-AR subtypes, in this study,
      we evaluated the skeletal phenotype of mice with single-gene inactivation of
      alpha2A-AR (alpha2A-AR-/-), and the effect of daily treatment with a
      supraphysiological dose of T3, for 4 or 12 weeks, on bone microarchitecture and
      bone resistance to fracture. Micro-computed tomographic (MUCT) analysis revealed
      normal trabecular and cortical bone structure in the femur and vertebra of
      euthyroid alpha2A-AR-/- mice. Thyrotoxicosis was more detrimental to femoral
      trabecular bone in alpha2A-AR-/- than in WT mice, whereas this bone compartment
      had been previously shown to present resistance to thyrotoxicosis in alpha2C-AR-/
      mice. Altogether these findings reveal that TH excess depends on alpha2C-AR
      signaling to negatively affect femoral trabecular bone. In contrast,
      thyrotoxicosis was more deleterious to femoral and vertebral cortical bone in WT
      than in alpha2A-AR-/- mice, suggesting that alpha2A-AR signaling contributes to
      TH actions on cortical bone. These findings further support a TH-SNS interaction
      to control bone physiology, and suggest that alpha2A-AR and alpha2C-AR signaling
      pathways have key roles in the mechanisms through which thyrotoxicosis promotes
      its detrimental effects on bone remodeling, structure and resistance to fracture.

PMID- 30233490
TI  - The "A to Z" of Managing Type 2 Diabetes in Culturally Diverse Populations.
AB  - Type 2 diabetes affects racial/ethnic minorities at an alarming rate in the US
      and in many countries around the world. The quality of health care provided to
      these groups is often suboptimal, resulting in worse patient-related outcomes
      when compared to those in mainstream populations. Understanding the complex
      biological elements that influence the development and course of the disease in
      high-risk populations is extremely important but often insufficient to implement
      effective prevention and treatment plans. Multiple factors must be addressed in
      routine diabetes clinical care. This paper discusses various key factors,
      organized in alphabetical order. These are acculturation, biology, clinician's
      cultural awareness, depression and diabetes-specific emotional distress,
      educational level, fears, group integration, health literacy, intimacy and sexual
      dysfunction, judging, knowledge of the disease, language, medication adherence,
      nutritional preferences, other forms of medicine (alternative), perception of
      body image, quality of life, religion and faith, socio-economic status,
      technology, unconscious bias, vulnerable groups, asking why?, exercise, "you are
      in charge" and zip it! Considering these factors in the development of type 2
      diabetes prevention and treatment programs will help improve diabetes-related
      outcomes in culturally diverse populations and reduce health care disparities.

PMID- 30233493
TI  - Aberrant Splicing Is the Pathogenicity Mechanism of the p.Glu314Lys Variant in
      CYP11A1 Gene.
AB  - Context: The cholesterol side chain cleavage enzyme (CYP11A1) catalyzes the
      conversion of cholesterol to pregnenolone, the first rate-limiting step of
      steroidogenesis. CYP11A1 mutations are associated with primary adrenal
      insufficiency (PAI) as well as disorders of sex development (DSD) in 46,XY
      patients. Objective: To define the pathogenicity mechanism for the p.Glu314Lys
      variant, previously reported, and found in four additional patients with CYP11A1
      deficiency. Subjects and Methods: DNA of four patients presenting with delayed
      PAI and/or 46,XY DSD were studied by Sanger or Massively Parallel sequencing.
      Three CYP11A1 mutations were characterized in vitro and in silico, and one by
      mRNA analysis on testicular tissue. Results: All patients were compound
      heterozygous for the previously described p.Glu314Lys variant. In silico studies
      predicted this mutation as benign with no effect on splicing but mRNA analysis
      found that it led to incomplete exon 5 skipping. This mechanism was confirmed by
      minigene experiment. The protein carrying this mutation without exon skipping
      should conserve almost normal activity, according to in vitro studies. Two other
      mutations found in trans, the p.Arg120Gln and p.Arg465Trp, had similar activity
      compared to negative control, consistent with the in silico studies. Conclusions:
      We provide biological proof that the p. Glu314Lys variant is pathogenic due to
      its impact on splicing and seems responsible for the moderate phenotype of the
      four patients reported herein. The present study highlights the importance of
      considering the potential effect of a missense variant on splicing when it is not
      predicted to be disease causing.

PMID- 30233492
TI  - The Retinol Circulating Complex Releases Hormonal Ligands During Acute Stress
      Disorders.
AB  - Intensive care workers actively participate in very hot debates aiming at
      defining the true metabolic, hormonal and nutritional requirements of critically
      ill patients, the contributory roles played by thyroid and retinoid ligands being
      largely underestimated. The present article makes up for redressing the balance
      on behalf of these last hormonal compounds. The retinol circulating complex is
      transported in the bloodstream in the form of a trimolecular edifice made up of
      transthyretin (TTR), retinol-binding protein (RBP) and its retinol ligand. TTR
      reflects the size of the lean body mass (LBM) and is one of the 3 carrier
      proteins of thyroid hormones whereas RBP is the sole conveyor of retinol in human
      plasma. In acute inflammatory disorders, both TTR and RBP analytes experience
      abrupt cytokine-induced suppressed hepatic synthesis whose amplitude is dependent
      on the duration and severity of the inflammatory burden. The steep drop in TTR
      and RBP plasma values releases thyroxine and retinol ligands in their
      physiologically active forms, creating free pools estimated to be 10-20 times
      larger than those described in healthy subjects. The peak endocrine influence is
      reached on day 4 and the freed ligands undergo instant cellular overconsumption
      and urinary leakage of unmetabolized fractions. As a result of these transient
      hyperthyroid and hyperretinoid states, helpful stimulatory and/or inhibitory
      processes are set in motion, operating as second frontlines fine-tuning the
      impulses primarily initiated by cytokines. The data explain why preexisting
      protein malnutrition, as assessed by subnormal LBM and TTR values, impairs the
      development of appropriate recovery processes in critically ill patients. These
      findings have survival implications, emphasizing the need for more adapted
      therapeutic strategies in intensive care units.

PMID- 30233494
TI  - Efficacy of Metformin for Benign Thyroid Nodules in Subjects With Insulin
      Resistance: A Systematic Review and Meta-Analysis.
AB  - Background: To evaluate the effect of metformin therapy on decreasing benign
      thyroid nodule volume in subjects with insulin resistance (IR). Method:
      Randomized controlled trials (RCTs) and self-controlled trials for the meta
      analysis published, before January 31, 2018 were selected from the PubMed,
      Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database,
      National Knowledge Infrastructure, WANFANG and VIP Database. Pooled standard mean
      difference with 95% confidence interval was estimated by fixed- or random-effects
      model depending on heterogeneity. The risk of bias using the Cochrane
      Collaboration's tool was used to assess the quality of the RCTs contained. The
      quality of self-controlled studies was evaluated using the Methodological index
      for non-randomized studies (MINORS) method. Results: 7 studies (3 RCTs and 4
      prospective self-controlled studies) with 240 patients were considered to be
      appropriate for the meta-analysis. The results of the meta-analysis indicated
      that the volume of thyroid nodule decreased significantly after metformin therapy
      (SMD -0.62, 95% CI -0.98 ~ -0.27). 6 studies reported the changes of the level of
      TSH. TSH levels decreased significantly after metformin therapy (SMD -0.27, 95%
      CI -0.47 ~ -0.07). The pooled data indicated an increase in FT3 level, and an
      unchanged FT4 level after metformin therapy (FT3, SMD 0.25, 95% CI 0.05 ~ 0.45;
      FT4, SMD -0.07, 95% CI -0.27 ~ 0.13). HOMA-IR levels decreased significantly
      after metformin therapy based on the pooled results of 3 RCTs and 3 prospective
      self-controlled studies (SMD -1.08, 95% CI -1.69 ~ -0.47). Conclusion: The meta
      analysis demonstrated that metformin was safe and useful in shrinking benign
      thyroid nodules volume, improving thyroid function and IR. A large number of high
      quality prospective studies still need to be carried out.

PMID- 30233496
TI  - The Implications of Vitamin D Status During Pregnancy on Mother and her
      Developing Child.
AB  - Pregnancy is a time of tremendous growth and physiological changes for mother and
      her developing fetus with lifelong implications for the child. The concert of
      actions that must occur so mother does not reject the foreign tissue of the fetus
      is substantial. There must be exquisite balance between maternal tolerance to
      these foreign proteins of paternal origin but also immune surveillance and
      function such that the mother is not immunocompromised. When this process goes
      awry, the mother may experience such pregnancy complications as preeclampsia and
      infections. Vitamin D deficiency affects these processes. Controversy continues
      with regard to the optimal daily intake of vitamin D, when sunlight exposure
      should be taken into account, and how to define sufficiency during such
      vulnerable and critical periods of development. The importance of vitamin D
      supplementation during pregnancy in preventing some of the health risks to the
      mother and fetus appears linked to achieving 25(OH)D concentrations >40 ng/mL,
      the beginning point of the plateau where conversion of the vitamin D metabolite
      25(OH)D, the pre-hormone, to 1,25(OH)2D, the active hormone, is optimized.
      Throughout pregnancy, the delivery of adequate vitamin D substrate-through
      sunlight or supplement-is required to protect both mother and fetus, and when in
      sufficient supply, favorably impacts the epigenome of the fetus, and in turn,
      long term health. There is a growing need for future research endeavors to focus
      not only on critical period(s) from pre-conception through pregnancy, but
      throughout life to prevent certain epigenetic changes that adversely affect
      health. There is urgency based on emerging research to correct deficiency and
      maintain optimal vitamin D status. The impact of vitamin D and its metabolites on
      genetic signaling during pregnancy in both mother and fetus is an area of great
      activity and still in its early stages. While vitamin D repletion during
      pregnancy minimizes the risk of certain adverse outcomes (e.g., preterm birth,
      asthma, preeclampsia, and gestational diabetes), the mechanisms of how these
      processes occur are not fully understood. As we intensify our research efforts in
      these areas. it is only a matter of time that such mechanisms will be defined.

PMID- 30233497
TI  - A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism.
AB  - Thyroid dysfunction, manifesting as either overt or subclinical hypothyroidism,
      negatively affects lipid metabolism: this leads to hypercholesterolemia which
      progressively increases the risk for cardiovascular disease and, potentially,
      mortality. Hypercholesterolemia in hypothyroidism is mainly due to a reduction in
      low-density lipoprotein (LDL) receptor activity, this accompanied by concomitant
      diminishing control by triiodothyronine (T3) of sterol regulatory element-binding
      protein 2 (SREBP-2), which modulates cholesterol biosynthesis by regulating rate
      limit degrading enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA)
      activity. Recently, 3,5-diiodothyronine (T2), a natural thyroid hormone
      derivative, was found to repress the transcription factor carbohydrate-response
      element-binding protein (ChREBP) and also to be involved in lipid catabolism and
      lipogenesis, though via a different pathway than that of T3. While thyroid
      hormone could therapeutically reverse the dyslipidemic profile commonly occurring
      in hypothyroidism, it should be borne in mind that the potency of the effects may
      be age-and sex-dependent. Thyroid hormone administration possibly also sustains
      and enhances the efficacy of hypolipidemic drugs, such as statins, ezetimibe and
      proprotein convertase subtilisin/kexin type 9 (PCSK9), in patients with
      dyslipidemia and hypothyroidism.

PMID- 30233498
TI  - Developmental Exposure to Endocrine Disrupting Chemicals and Type 1 Diabetes
      Mellitus.
AB  - Exposure to endocrine disrupting chemicals (EDCs) may have implications for the
      development of type 1 diabetes mellitus (T1DM), especially if exposure occurs
      during development. Exposure to EDCs during fetal or early life can disrupt the
      development of both the immune system and the pancreatic beta cells, potentially
      increasing susceptibility to T1DM later in life. Developmental exposure to some
      EDCs can cause immune system dysfunction, increasing the risk of autoimmunity. In
      addition, developmental exposure to some EDCs can affect beta cell development
      and function, influencing insulin secretion. These changes may increase stress on
      the beta cells, and identify them as a target to the immune system. Developmental
      exposure to EDCs that disrupt metabolism by increasing insulin resistance or
      obesity may also stress the beta cells. Exposure to these EDCs during development
      may play a role in the pathogenesis of T1DM, and requires further research.

PMID- 30233495
TI  - Links Between Obesity-Induced Brain Insulin Resistance, Brain Mitochondrial
      Dysfunction, and Dementia.
AB  - It is widely recognized that obesity and associated metabolic changes are
      considered a risk factor to age-associated cognitive decline. Inflammation and
      increased oxidative stress in peripheral areas, following obesity, are patently
      the major contributory factors to the degree of the severity of brain insulin
      resistance as well as the progression of cognitive impairment in the obese
      condition. Numerous studies have demonstrated that the alterations in brain
      mitochondria, including both functional and morphological changes, occurred
      following obesity. Several studies also suggested that brain mitochondrial
      dysfunction may be one of underlying mechanism contributing to brain insulin
      resistance and cognitive impairment in the obese condition. Thus, this review
      aimed to comprehensively summarize and discuss the current evidence from various
      in vitro, in vivo, and clinical studies that are associated with obesity, brain
      insulin resistance, brain mitochondrial dysfunction, and cognition. Contradictory
      findings and the mechanistic insights about the roles of obesity, brain insulin
      resistance, and brain mitochondrial dysfunction on cognition are also presented
      and discussed. In addition, the potential therapies for obese-insulin resistance
      are reported as the therapeutic strategies which exert the neuroprotective
      effects in the obese-insulin resistant condition.

PMID- 30233500
TI  - Improved Glucose and Lipid Metabolism in the Early Life of Female Offspring by
      Maternal Dietary Genistein Is Associated With Alterations in the Gut Microbiota.
AB  - Maternal over-nutrition can lead to metabolic disorders in offspring, whereas
      maternal dietary genistein may have beneficial effects on the metabolic health of
      offspring. Our objective was to determine whether maternal dietary genistein
      could attenuate the detrimental effects of a maternal high-fat diet on their
      offspring's metabolism and to explore the role of the gut microbiota on their
      offspring's glucose and lipid metabolism. C57BL/6 female mice were fed either a
      high-fat diet without genistein (HF), high-fat diet with low-dose genistein (0.25
      g/kg diet) (HF.LG), high-fat diet with high-dose genistein (0.6 g/kg diet)
      (HF.HG) or normal control diet (Control) for 3 weeks prior to breeding and
      throughout gestation and lactation. The female offspring in the HF group had
      lower birth weights and glucose intolerance and higher serum insulin,
      triacylglycerol (TG) and total cholesterol (TC) levels at weaning compared with
      the Control group. Offspring from HF.LG dams had increased birth weight, improved
      glucose tolerance, and decreased fasting insulin, whereas the serum TG and TC
      levels were decreased in HF.HG offspring in comparison with HF offspring. The
      significant enrichment of Bacteroides and Akkermansia in offspring from genistein
      fed dams might play vital roles in improving glucose homeostasis and insulin
      sensitivity, and the significantly increased abundance of Rikenella and
      Rikenellaceae_RC9_ gut_group in the HF.HG group may be associated with the
      decreased serum levels of TG and TC. In conclusion, maternal dietary genistein
      negates the harmful effects of a maternal high-fat diet on glucose and lipid
      metabolism in female offspring, in which the altered gut microbiota plays crucial
      roles. The ability of maternal genistein intake to improve offspring metabolism
      is important since this intervention could fight the transmission of diabetes to
      subsequent generations.

PMID- 30233501
TI  - The Effect of Strain Level Diversity on Robust Inference of Virus-Induced
      Mortality of Phytoplankton.
AB  - Infection and lysis of phytoplankton by viruses affects population dynamics and
      nutrient cycles within oceanic microbial communities. However, estimating the
      quantitative rates of viral-induced lysis remains challenging in situ. The
      modified dilution method is the most commonly utilized empirical approach to
      estimate virus-induced killing rates of phytoplankton. The lysis rate estimates
      of the modified dilution method are based on models which assume virus-host
      interactions can be represented by a single virus and a single host population
      with homogeneous life-history traits. Here, using modeling approaches, we examine
      the robustness of the modified dilution method in multi-strain, complex
      communities. We assume that strains differ in their life history traits,
      including growth rates (of hosts) and lysis rates (by viruses). We show that
      trait differences affect resulting experimental dynamics such that lysis rates
      measured using the modified dilution method may be driven by the fastest
      replicating strains; which are not necessarily the most abundant in situ. We
      discuss the implications of using the modified dilution method and alternative
      dilution-based approaches for estimating viral-induced lysis rates in marine
      microbial communities.

PMID- 30233499
TI  - Insulin Resistance in HIV-Patients: Causes and Consequences.
AB  - Here we review how immune activation and insulin resistance contribute to the
      metabolic alterations observed in HIV-infected patients, and how these
      alterations increase the risk of developing CVD. The introduction and evolution
      of antiretroviral drugs over the past 25 years has completely changed the
      clinical prognosis of HIV-infected patients. The deaths of these individuals are
      now related to atherosclerotic CVDs, rather than from the viral infection itself.
      However, HIV infection, cART, and intestinal microbiota are associated with
      immune activation and insulin resistance, which can lead to the development of a
      variety of diseases and disorders, especially with regards to CVDs. The increase
      in LPS and proinflammatory cytokines circulating levels and intracellular
      mechanisms activate serine kinases, resulting in insulin receptor substrate-1
      (IRS-1) serine phosphorylation and consequently a down regulation in insulin
      signaling. While lifestyle modifications and pharmaceutical interventions can be
      employed to treat these altered metabolic functions, the mechanisms involved in
      the development of these chronic complications remain largely unresolved. The
      elucidation and understanding of these mechanisms will give rise to new classes
      of drugs that will further improve the quality of life of HIV-infected patients,
      over the age of 50.

PMID- 30233502
TI  - The Influence of Microwave Sterilization on the Ultrastructure, Permeability of
      Cell Membrane and Expression of Proteins of Bacillus Cereus.
AB  - Bacillus cereus was isolated from ready-to-serve brine goose, identified by 16S
      rRNA gene sequencing analysis and treated with a commercial microwave
      sterilization condition (a power of 1,800 W at 85 degrees C for 5 min). The
      influence of microwaves on the morphology, the permeability of membrane and the
      expression of total bacterial proteins was observed. Microwave induced the clean
      of bacterial nuclear chromatin, increased the permeability and disrupted the
      integrity of membrane. Twenty-three proteins including 18 expressed down
      regulated proteins and 5 expressed up-regulated proteins were identified by HPLC
      MS/MS in the samples treated with microwave. The frequencies of proteins changed
      after microwaves treatment were labeled as 39.13% (synthesis and metabolism of
      amino acid or proteins), 21.74% (carbohydrate metabolism), 8.70% (anti-oxidant
      and acetyl Co-A synthesis), and 4.35% (the catalyst of catabolism of bacterial
      acetoin, ethanol metabolism, glyoxylate pathway, butyrate synthesis and
      detoxification activity), respectively. This study indicates that microwaves
      result in the inactivation of Bacillus cereus by cleaning nuclear chromatin,
      disrupting cell membrane and disordering the expression of proteins.

PMID- 30233504
TI  - Production and Antimicrobial Activity of Nisin Under Enological Conditions.
AB  - Lactic acid bacteria (LAB) are responsible for the malolactic fermentation of
      wines, and, therefore, controlling the growth of these bacteria is a key factor
      for elaborating premium wines. Sulfur dioxide has been traditionally used as an
      efficient antimicrobial and antioxidant agent, however, nowadays consumers'
      demand tends toward a reduction of sulfur dioxide levels in wine and other
      fermented foods. A previous study of our research group had demonstrated the
      effectiveness of the bacteriocin nisin to inhibit the growth of enological LAB,
      and its activity had been tested in culture broths. The aim of this study was to
      investigate the possibility of controlling the growth of bacteria in wine by the
      use of nisin in combination with sulfur dioxide, and to study nisin production by
      the natural producer Lactococcus lactis LM29 under enological conditions. Our
      results showed that L. lactis LM29 produced nisin in the presence of 2 and 4%
      ethanol (v/v), while higher concentrations of ethanol fully inhibited the
      production of nisin. We obtained a nisin enriched active extract (NAE) from the
      cell-free supernatant of a culture of L. lactis LM29 in MRS broth containing 60%
      (v/v) sterile grape juice, and the extract was fully active in inhibiting the
      growth of the enological LAB tested by the microtiter method. Moreover, the nisin
      concentration of the obtained NAE could actually prevent the formation of an
      undesirable biofilm of LAB strains. Finally, our results of wine ageing under
      winery conditions showed that the use of 50 mg/L nisin decreased fourfold the
      concentration of sulfur dioxide required to prevent LAB growth in the wines.

PMID- 30233503
TI  - Identification of Halophilic Microbes in Lung Fibrotic Tissue by Oligotyping.
AB  - Idiopathic pulmonary fibrosis (IPF) is an incurable disease with poor prognosis
      and unknown etiology. The poor clinical outcome is associated with enhanced
      microbial burden in bronchoalveolar lavage fluid from IPF patients. However,
      whether microbes from the respiratory tract fluid cause the disease remains
      uncertain. Tissue-associated microbes can influence host physiology in health and
      disease development. The aim of this study was to evaluate the existence of
      microbes in lung fibrotic tissues. We evaluated the microbial community in lung
      tissues from IPF and from human transforming growth factor-beta1 (TGF-beta1)
      transgenic mice with lung fibrosis by oligotyping. We also evaluated the
      microbial population in non-tumor-bearing tissues from surgical specimens of lung
      cancer patients. The phyla Firmicutes and the genus Clostridium tended to be
      predominant in the lung tissue from IPF and lung cancer patients. Oligotyping
      analysis revealed a predominance of bacteria belonging to the genera Halomonas,
      Shewanella, Christensenella, and Clostridium in lung tissue from IPF and lung
      cancer. Evaluation of the microbial community in the lung tissue from mice
      revealed abundance of Proteobacteria in both wild-type (WT) littermates and
      transgenic mice. However, the genus Halomonas tended to be more abundant in TGF
      beta1 transgenic mice compared to WT mice. In conclusion, this study describes
      tissue-associated microbes in lung fibrotic tissues from IPF patients and from
      aging TGF-beta1 transgenic mice.

PMID- 30233506
TI  - Editorial: Progress in Ecological Stoichiometry.

PMID- 30233505
TI  - Comparison of Highly and Weakly Virulent Dickeya solani Strains, With a View on
      the Pangenome and Panregulon of This Species.
AB  - Bacteria belonging to the genera Dickeya and Pectobacterium are responsible for
      significant economic losses in a wide variety of crops and ornamentals. During
      last years, increasing losses in potato production have been attributed to the
      appearance of Dickeya solani. The D. solani strains investigated so far share
      genetic homogeneity, although different virulence levels were observed among
      strains of various origins. The purpose of this study was to investigate the
      genetic traits possibly related to the diverse virulence levels by means of
      comparative genomics. First, we developed a new genome assembly pipeline which
      allowed us to complete the D. solani genomes. Four de novo sequenced and ten
      publicly available genomes were used to identify the structure of the D. solani
      pangenome, in which 74.8 and 25.2% of genes were grouped into the core and
      dispensable genome, respectively. For D. solani panregulon analysis, we performed
      a binding site prediction for four transcription factors, namely CRP, KdgR, PecS
      and Fur, to detect the regulons of these virulence regulators. Most of the D.
      solani potential virulence factors were predicted to belong to the accessory
      regulons of CRP, KdgR, and PecS. Thus, some differences in gene expression could
      exist between D. solani strains. The comparison between a highly and a low
      virulent strain, IFB0099 and IFB0223, respectively, disclosed only small
      differences between their genomes but significant differences in the production
      of virulence factors like pectinases, cellulases and proteases, and in their
      mobility. The D. solani strains also diverge in the number and size of prophages
      present in their genomes. Another relevant difference is the disruption of the
      adhesin gene fhaB2 in the highly virulent strain. Strain IFB0223, which has a
      complete adhesin gene, is less mobile and less aggressive than IFB0099. This
      suggests that in this case, mobility rather than adherence is needed in order to
      trigger disease symptoms. This study highlights the utility of comparative
      genomics in predicting D. solani traits involved in the aggressiveness of this
      emerging plant pathogen.

PMID- 30233508
TI  - Complete Genome Sequence and Characterization of a Protein-Glutaminase Producing
      Strain, Chryseobacterium proteolyticum QSH1265.
AB  - Recently, an enzyme named protein-glutaminase (PG) has been identified as a new
      type of enzyme with significant potential for deamidation of food proteins. The
      enzyme is shown to be expressed as a pre-pro-protein with a putative signal
      peptide of 21 amino acids, a pro-sequence of 114 amino acids, and a mature PG of
      185 amino acids. The microbial enzyme PG specifically catalyzes deamidation of
      proteins without protein hydrolysis pretreatment and only reacts with glutamine
      residues in the side-chains of proteins or long peptides. All these attributes
      suggest that it has a great potential for food industrial applications. However,
      until recently, there have been relatively few studies of the PG-producing
      strains. A strain named Chryseobacterium proteolyticum QSH1265 which can produce
      PG was isolated from a soil sample collected in Songjiang, Shanghai, China. Its
      enzyme activity was about 0.34 +/- 0.01 U/mL when using carboxybenzoxy-Gln-Gly as
      a substrate. The strain can produce acid from D-glucose, maltose, L-arabinose
      sucrose, glycerol, and mannitol but not fructose, and it is also positive for
      indole production and urease. Here we describe the complete genome sequence of
      this strain via PacBio RSII sequencing. The C. proteolyticum QSH1265 genome
      consists of a circular chromosome with total length of 4,849,803 bp without any
      plasmids. All of 4563 genes were predicted including 4459 genes for protein
      coding and 104 RNA-relative genes with an average G+C content of 36.16%. The KEGG
      and COG annotation provide information for the specific function of proteins
      encoded in the genome, such as proteases, chromoproteins, stress proteins,
      antiporters, etc. A highly conserved hypothetical protein shares a promoter with
      the gene encoding the protein-glutaminase enzyme. The genome sequence and
      preliminary annotation provide valuable genetic information for further study of
      C. proteolyticum.

PMID- 30233507
TI  - Modulation of Tomato Response to Rhizoctonia solani by Trichoderma harzianum and
      Its Secondary Metabolite Harzianic Acid.
AB  - The present study investigated the transcriptomic and metabolomic changes
      elicited in tomato plants (Solanum lycopersicum cv. Micro-Tom) following
      treatments with the biocontrol agent Trichoderma harzianum strain M10 or its
      purified secondary metabolite harzianic acid (HA), in the presence or the absence
      of the soil-borne pathogen Rhizoctonia solani. Transcriptomic analysis allowed
      the identification of differentially expressed genes (DEGs) that play a pivotal
      role in resistance to biotic stress. Overall, the results support the ability of
      T. harzianum M10 to activate defense responses in infected tomato plants. An
      induction of hormone-mediated signaling was observed, as shown by the up
      regulation of genes involved in the ethylene and jasmonate (ET/JA) and salicylic
      acid (SA)-mediated signaling pathways. Further, the protective action of T.
      harzianum on the host was revealed by the over-expression of genes able to
      detoxify cells from reactive oxygen species (ROS). On the other hand, HA
      treatment also stimulated tomato response to the pathogen by inducing the
      expression of several genes involved in defense response (including protease
      inhibitors, resistance proteins like CC-NBS-LRR) and hormone interplay. The
      accumulation of steroidal glycoalkaloids in the plant after treatments with
      either T. harzianum or HA, as determined by metabolomic analysis, confirmed the
      complexity of the plant response to beneficial microbes, demonstrating that these
      microorganisms are also capable of activating the chemical defenses.

PMID- 30233510
TI  - Bacterial Subspecies Variation and Nematode Grazing Change P Dynamics in the
      Wheat Rhizosphere.
AB  - Low phosphorus soils are thought to constitute the majority of soils worldwide
      and cannot support intensive agriculture without high fertilizer inputs.
      Rhizobacteria are well-known to modify P dynamics and an increased bacterial
      diversity normally has a positive impact on various process rates. However, it is
      not known how variation in bacterial diversity at the subspecies level could
      influence trophic interactions in the rhizosphere and its consequences on plant P
      nutrition. We therefore hypothesized that the interactions between closely
      related P solubilizing bacteria and their grazing nematodes could improve plant P
      dynamics from an unavailable P source. We isolated four Pseudomonas poae strains
      and extracted nematodes from a Saskatchewan wheat field soil sample. The
      potential of all bacterial isolates with and without nematodes for increasing P
      availability in the wheat rhizosphere was tested in controlled microcosms with
      Ca3(PO4)2 as sole P source. Liberated P, phosphatase activity, plant P and
      bacterial abundance based on phnX gene copies were determined. Phosphorus
      solubilization efficiency of isolates varied between isolates whereas phosphatase
      enzyme activity was only detected under nematodes grazing and during the first 15
      days of the experiment. Nematodes grazing upon individual Pseudomonas poae
      increased phosphatase enzyme activity, bacterial abundance, but decreased plant P
      concentration compared to non-grazed system. In contrast, the treatment combining
      all Pseudomonas poae isolates together with nematodes resulted in significant
      increases in P availability and plant P concentration. Diverse P-solubilizing
      efficiency and interaction with nematodes within the same bacterial "species"
      suggest that P dynamics might be linked to micro variation in soil diversity that
      would not accurately be picked up using common tools such as 16S rRNA gene
      sequencing.

PMID- 30233509
TI  - Source Attribution of Foodborne Diseases: Potentialities, Hurdles, and Future
      Expectations.

PMID- 30233511
TI  - Assessment of Bacterial Communities Associated With the Skin of Costa Rican
      Amphibians at La Selva Biological Station.
AB  - Amphibian skin is a suitable environment for rich communities of microorganisms,
      both beneficial and detrimental to the host. The amphibian cutaneous microbiota
      has been hypothesized to play an important role as symbionts, protecting their
      hosts against disease. Costa Rica has one of the most diverse assemblages of
      amphibians in the world and we know very little about the microbiota of these
      tropical animals. For comparison with other studies, we explore the diversity of
      the skin bacterial communities employing16S rRNA amplicon sequencing of swab
      samples from twelve species of frogs at La Selva Biological Station in Sarapiqui,
      Heredia province. The predominant phylum detected in our studies was
      Proteobacteria, followed by Bacteroidetes and Actinobacteria, with these three
      phyla representing 89.9% of the total bacterial taxa. At the family level,
      Sphingobacteriaceae and Comamonadaceae were highly represented among samples. Our
      results suggest that host species and host family are significant predictors of
      the variation in microbiota composition. This study helps set the foundation for
      future research about microbiota composition and resilience to unfavorable
      conditions, leading to improvement in managing strategies for endangered
      amphibian species.

PMID- 30233512
TI  - A Galacto-Oligosaccharides Preparation Derived From Lactulose Protects Against
      Colorectal Cancer Development in an Animal Model.
AB  - Colorectal cancer (CRC) is one of the most common neoplasias worldwide, and its
      incidence is increasing. Consumption of prebiotics is a useful strategy in order
      to prevent this important disease. These nutraceutical compounds might exert
      protective biological functions as antitumors. In order to test the
      chemopreventive effect of GOS-Lu (galacto-oligosaccharides derived from
      lactulose) prebiotic preparation against this cancer, an animal model (Rattus
      norvegicus F344) was used. In this model, two doses of azoxymethane (10 mg/kg)
      and two treatments with dextran sodium sulfate (DSS) were administered to the
      animals. Animals were fed for 20 weeks, and either control drinking water or
      drinking water containing 10% (w/w) GOS-Lu prebiotic preparation was provided to
      them. Animals were sacrificed after those 20 weeks, and their digestive tract
      tissues were analyzed. The results revealed a statistically significant reduction
      in the number of colon tumors in the GOS-Lu cohort with respect to control
      animals. Metagenomics sequencing was used for studying colon microbiota
      populations, revealing significant reductions in populations of pro-inflammatory
      bacteria families and species, and significant increases in interesting
      beneficial populations, such as Bifidobacterium. Therefore, oral administration
      of the prebiotic GOS-Lu preparation may be an effective strategy for preventing
      CRC.

PMID- 30233513
TI  - Global Deletome Profile of Saccharomyces cerevisiae Exposed to the Technology
      Critical Element Yttrium.
AB  - The emergence of the technology-critical-element yttrium as a contaminant in the
      environment raises concern regarding its toxicological impact on living
      organisms. The molecular mechanisms underlying yttrium toxicity must be
      delineated. We considered the genomic phenotyping of a mutant collection of
      Saccharomyces cerevisiae to be of particular interest to decipher key cellular
      pathways involved either in yttrium toxicity or detoxification mechanisms. Among
      the 4733 mutants exposed to yttrium, 333 exhibited modified growth, of which 56
      were sensitive and 277 were resistant. Several functions involved in yttrium
      toxicity mitigation emerged, primarily vacuolar acidification and retrograde
      transport. Conversely, functional categories overrepresented in the yttrium
      toxicity response included cytoskeleton organization and endocytosis, protein
      transport and vesicle trafficking, lipid metabolism, as well as signaling
      pathways. Comparison with similar studies carried out using other metals and
      stressors showed a response pattern similar to nickel stress. One third of the
      identified mutants highlighted peculiar cellular effects triggered by yttrium,
      specifically those affecting the pheromone-dependent signaling pathway or
      sphingolipid metabolic processes. Taken together, these data emphasize the role
      of the plasma membrane as a hotspot for yttrium toxicity. The up-to-now lack of
      data concerning yttrium toxicity at the cellular and molecular levels makes this
      pioneer study using the model S. cerevisiae an excellent first basis for the
      assessment of yttrium toxicity toward eukaryotes.

PMID- 30233514
TI  - Vertical Transmission of Wolbachia Is Associated With Host Vitellogenin in
      Laodelphax striatellus.
AB  - Wolbachia in host germ lines are essential for their vertical transmission to the
      next generation. It is unclear how the regulation of host oocyte development
      influences Wolbachia location and the mechanistic basis of transmission. Here, we
      investigated whether vitellogenin influences Wolbachia transmission in Laodelphax
      striatellus. Wolbachia increased in density and spread from the anterior
      tropharium to developing oocytes as ovaries developed. Microscopic observations
      indicated that Wolbachia invaded ovarioles from the tropharium of its anterior
      side rather than the pedicel side. Wolbachia utilized the host Vg transovarial
      transportation system to enter the ovaries and were transmitted from the
      tropharium into the developing oocytes through nutritive cords. These
      observations were supported by knocking down the Vg transcript, in which low
      Wolbachia titers were detected in ovaries and fewer Wolbachia were transmitted
      into oocytes. Our findings establish a link between the Vg-related mode of
      transovarial transmission and efficient maternal transmission of Wolbachia.

PMID- 30233515
TI  - The DnaA AAA+ Domain His136 Residue Directs DnaB Replicative Helicase to the
      Unwound Region of the Replication Origin, oriC.
AB  - Chromosomal replication initiation requires dynamic mechanisms in higher-order
      nucleoprotein complexes that are constructed at the origin of replication. In
      Escherichia coli, DnaA molecules construct functional oligomers at the origin
      oriC, enabling localized unwinding of oriC and stable binding of DnaB helicases
      via multiple domain I molecules of oriC-bound DnaA. DnaA-bound DnaB helicases are
      then loaded onto the unwound region of oriC for construction of a pair of
      replisomes for bidirectional replication. However, mechanisms of DnaB loading to
      the unwound oriC remain largely elusive. In this study, we determined that His136
      of DnaA domain III has an important role in loading of DnaB helicases onto the
      unwound oriC. DnaA H136A mutant protein was impaired in replication initiation in
      vivo, and in DnaB loading to the unwound oriC in vitro, whereas the protein fully
      sustained activities for oriC unwinding and DnaA domain I-dependent stable
      binding between DnaA and DnaB. Functional and structural analyses supported the
      idea that transient weak interactions between DnaB helicase and DnaA His136
      within specific protomers of DnaA oligomers direct DnaB to a region in close
      proximity to single stranded DNA at unwound oriC bound to DnaA domain III of the
      DnaA oligomer. The aromatic moiety of His136 is basically conserved at
      corresponding residues of eubacterial DnaA orthologs, implying that the guidance
      function of DnaB is common to all eubacterial species.

PMID- 30233516
TI  - The Response of Rhodotorula mucilaginosa to Patulin Based on Lysine
      Crotonylation.
AB  - Patulin (PAT) is a mycotoxin produced by some Penicillium, Aspergillus, and
      Byssochlamys species. Rhodotorula mucilaginosa is able to degrade PAT in vivo as
      well as in vitro, up till date, the process and molecular mechanism(s) involved
      patulin degradation still remains unknown. Protein lysine crotonylation (Kcr)
      plays an important role in regulating chromatin dynamics, gene expression, and
      metabolic pathways in mammals and eukaryotes. Investigation of the Kcr changes
      accompanying degradation of patulin in R. mucilaginosa were observed to
      investigate the mechanisms of patulin inhibition. Tandem mass tag (TMT) labeling
      and Kcro affinity enrichment, followed by high-resolution LC-MS/MS analysis, were
      used to perform quantitative lysine crotonylome analysis on R. mucilaginosa.
      Consequently, 1691 lysine crotonylation sites in 629 protein groups were
      identified, among which we quantified 1457 sites in 562 proteins. Among the
      quantified proteins, 79 and 46 crotonylated proteins were up-regulated and down
      regulated, respectively. The differentially up expressed modified proteins were
      mainly involved in tricarboxylic acid cycle and gluconeogenic pathway. The
      differentially down expressed Kcr proteins were mainly classified to ribosome and
      carbohydrate transport and metabolism. Bioinformatic analyses were performed to
      annotate the quantifiable lysine crotonylated targets. Moreover, interaction
      networks and high confidence domain architectures of crotonylated proteins were
      investigated with the aid of bioinformatic tools, and these results showed that
      there was an increase in the number of yeasts with crotonylated proteins. The
      results also provided information on the various roles of crotonylation, which
      are involved in PAT degradation.

PMID- 30233518
TI  - Effective Antimicrobial Activity of Green ZnO Nano Particles of Catharanthus
      roseus.
AB  - In the present study, zinc oxide nanoparticles (ZnO NPs) were synthesized using
      leaf extract of Catharanthus roseus (C. roseus) under different physical
      parameters. Biosynthesis of ZnO NPs was confirmed by UV-Visible spectrophotometer
      and further, characterized by X-Ray Diffraction (XRD), Fourier Transform Infrared
      spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron
      Microscopy (TEM), Energy-Dispersive X-ray spectroscopy (EDX), Atomic Force
      Microscopy (AFM), Photoluminescence study and Dynamic Light Scattering (DLS). We
      have also confirmed that several physical parameters such as pH, temperature,
      concentration of metal ions and reaction time were able to regulate shape and
      size of synthesized ZnO NPs. XRD and TEM analysis provided the information about
      the average size and hexagonal morphology of ZnO NPs. FTIR spectra analysis
      suggested that phenolic compounds played crucial role in the biosynthesis of ZnO
      NPs. The significant antibacterial activity of ZnO NPs was observed against
      Staphylococcus aureus MTCC 9760 (S. aureus), Streptococcus pyogenes MTCC 1926 (S.
      pyogenes), Bacillus cereus MTCC 430 (B. cereus), Pseudomonas aeruginosa MTCC 424
      (P. aeruginosa), Proteus mirabilis MTCC 3310 (P. mirabilis) and Escherichia coli
      MTCC 40 (E. coli). The synthesized ZnO NPs have shown antibacterial efficacy
      against both Gram-positive and Gram-negative pathogens. Synergistic effects of
      ZnO NPs and streptomycin showed increased efficacy as indicated by the increased
      zone of clearance in comparison to their individual effects (either ZnO NPs or
      streptomycin). Overall, the results elucidated a rapid, cost-effective,
      environmentally friendly and convenient method for ZnO NPs synthesis, which could
      be used as a potential antimicrobial agent against drug resistant microbes.

PMID- 30233517
TI  - Variant O89 O-Antigen of E. coli Is Associated With Group 1 Capsule Loci and
      Multidrug Resistance.
AB  - Bacterial surface polysaccharides play significant roles in fitness and
      virulence. In Gram-negative bacteria such as Escherichia coli, major surface
      polysaccharides are lipopolysaccharide (LPS) and capsule, representing O- and K
      antigens, respectively. There are multiple combinations of O:K types, many of
      which are well-characterized and can be related to ecotype or pathotype. In this
      investigation, we have identified a novel O:K permutation resulting through a
      process of major genome reorganization in a clade of E. coli. A multidrug
      resistant, extended-spectrum beta-lactamase (ESBL)-producing strain - E. coli
      26561 - represented a prototype of strains combining a locus variant of O89 and
      group 1 capsular polysaccharide. Specifically, the variant O89 locus in this
      strain was truncated at gnd, flanked by insertion sequences and located between
      nfsB and ybdK and we apply the term O89m for this variant. The prototype lacked
      colanic acid and O-antigen loci between yegH and hisI with this tandem
      polysaccharide locus being replaced with a group 1 capsule (G1C) which, rather
      than being a recognized E. coli capsule type, this locus matched to Klebsiella
      K10 capsule type. A genomic survey identified more than 200 E. coli strains which
      possessed the O89m locus variant with one of a variety of G1C types. Isolates
      from our collection with the combination of O89m and G1C all displayed a mucoid
      phenotype and E. coli 26561 was unusual in exhibiting a mucoviscous phenotype
      more recognized as a characteristic among Klebsiella strains. Despite the locus
      truncation and novel location, all O89m:G1C strains examined showed a ladder
      pattern typifying smooth LPS and also showed high molecular weight, alcian blue
      staining polysaccharide in cellular and/or extra-cellular fractions. Expression
      of both O-antigen and capsule biosynthesis loci were confirmed in prototype
      strain 26561 through quantitative proteome analysis. Further in silico
      exploration of more than 200 E. coli strains possessing the O89m:G1C combination
      identified a very high prevalence of multidrug resistance (MDR) - 85% possessed
      resistance to three or more antibiotic classes and a high proportion (58%) of
      these carried ESBL and/or carbapenemase. The increasing isolation of O89m:G1C
      isolates from extra-intestinal infection sites suggests that these represents an
      emergent clade of invasive, MDR E. coli.

PMID- 30233519
TI  - Characterization of a Prophage-Free Derivative Strain of Lactococcus lactis ssp.
      lactis IL1403 Reveals the Importance of Prophages for Phenotypic Plasticity of
      the Host.
AB  - Lactococcus lactis is a lactic acid bacterium of major importance for the dairy
      industry and for human health. Recent sequencing surveys of this species have
      provided evidence that all lactococcal genomes contain prophages and prophage
      like elements. The prophage-related sequences encompass up to 10% of the
      bacterial chromosomes and thus contribute significantly to the genetic diversity
      of lactococci. However, the impact of these resident prophages on the physiology
      of L. lactis is presently unknown. The genome of the first sequenced prototype
      strain, L. lactis ssp. lactis IL1403, contains six prophage-like elements which
      together represent 6.7% of the IL1403 chromosome. Diverse prophage genes other
      than those encoding phage repressors have been shown to be expressed in lysogenic
      conditions, suggesting that prophage genes are indeed able to modulate the
      physiology of their host. To elucidate the effect of resident prophages on the
      behavior of L. lactis in different growth conditions, we constructed and
      characterized, for the first time, a derivative strain of IL1403 that is prophage
      free. This strain provides unique experimental opportunities for the study of
      different aspects of lactococcal physiology using the well-defined genetic
      background of IL1403. Here, we show that resident prophages modify the growth and
      survival of the host strain to a considerable extent in different conditions,
      including in the gastrointestinal environment. They also may affect cellular
      autolytic properties and the host cells' susceptibility to virulent
      bacteriophages and antimicrobial agents. It thus appears that prophages
      contribute significantly to lactococcal cell physiology and might play an
      important role in the adaptation of L. lactis to cultivation and environmental
      conditions.

PMID- 30233520
TI  - Bacteriophages Contribute to Shaping Clostridioides (Clostridium) difficile
      Species.
AB  - Bacteriophages (phages) are bacterial viruses that parasitize bacteria. They are
      highly prevalent in nature, with an estimated 1031 viral particles in the whole
      biosphere, and they outnumber bacteria by at least 10-fold. Hence, phages
      represent important drivers of bacterial evolution, although our knowledge of the
      role played by phages in the mammalian gut is still embryonic. Several pathogens
      owe their virulence to the integrated phages (prophages) they harbor, which
      encode diverse virulence factors such as toxins. Clostridioides (Clostridium)
      difficile is an important opportunistic pathogen and several phages infecting
      this species have been described over the last decade. However, their exact
      contribution to the biology and virulence of this pathogen remains elusive.
      Current data have shown that C. difficile phages can alter virulence-associated
      phenotypes, in particular toxin production, by interfering with bacterial
      regulatory circuits through crosstalk with phage proteins for example. One phage
      has also been found to encode a complete binary toxin locus. Multiple regulatory
      genes have also been identified in phage genomes, suggesting that their impact on
      the host can be complex and often subtle. In this minireview, the current state
      of knowledge, major findings, and pending questions regarding C. difficile phages
      will be presented. In addition, with the apparent role played by phages in the
      success of fecal microbiota transplantation and the perspective of phage therapy
      for treatment of recurrent C. difficile infection, it has become even more
      crucial to understand what C. difficile phages do in the gut, how they impact
      their host, and how they influence the epidemiology and evolution of this
      clinically important pathogen.

PMID- 30233521
TI  - Interfering With DNA Decondensation as a Strategy Against Mycobacteria.
AB  - Tuberculosis is once again a major global threat, leading to more than 1 million
      deaths each year. Treatment options for tuberculosis patients are limited,
      expensive and characterized by severe side effects, especially in the case of
      multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is
      crucial to generate new therapeutic strategies. Using high resolution microscopy
      techniques, we discovered one such vulnerability of Mycobacterium tuberculosis.
      We demonstrate that the DNA of M. tuberculosis can condense under stressful
      conditions such as starvation and antibiotic treatment. The DNA condensation is
      reversible and specific for viable bacteria. Based on these observations, we
      hypothesized that blocking the recovery from the condensed state could weaken the
      bacteria. We showed that after inducing DNA condensation, and subsequent blocking
      of acetylation of DNA binding proteins, the DNA localization in the bacteria is
      altered. Importantly under these conditions, Mycobacterium smegmatis did not
      replicate and its survival was significantly reduced. Our work demonstrates that
      agents that block recovery from the condensed state of the nucleoid can be
      exploited as antibiotic. The combination of fusidic acid and inhibition of
      acetylation of DNA binding proteins, via the Eis enzyme, potentiate the efficacy
      of fusidic acid by 10 and the Eis inhibitor to 1,000-fold. Hence, we propose that
      successive treatment with antibiotics and drugs interfering with recovery from
      DNA condensation constitutes a novel approach for treatment of tuberculosis and
      related bacterial infections.

PMID- 30233523
TI  - Expression Profile of Glossina pallidipes MicroRNAs During Symptomatic and
      Asymptomatic Infection With Glossina pallidipes Salivary Gland Hypertrophy Virus
      (Hytrosavirus).
AB  - The Glossina pallidipes salivary gland hypertrophy virus (GpSGHV) infects tsetse
      flies predominantly asymptomatically and occasionally symptomatically.
      Symptomatic infections are characterized by overt salivary gland hypertrophy
      (SGH) in mass reared tsetse flies, which causes reproductive dysfunctions and
      colony collapse, thus hindering tsetse control via sterile insect technique
      (SIT). Asymptomatic infections have no apparent cost to the fly's fitness. Here,
      small RNAs were sequenced and profiles in asymptomatically and symptomatically
      infected G. pallidipes flies determined. Thirty-eight host-encoded microRNAs
      (miRNAs) were present in both the asymptomatic and symptomatic fly profiles,
      while nine host miRNAs were expressed specifically in asymptomatic flies versus
      10 in symptomatic flies. Of the shared 38 miRNAs, 15 were differentially
      expressed when comparing asymptomatic with symptomatic flies. The most up
      regulated host miRNAs in symptomatic flies was predicted to target immune-related
      mRNAs of the host. Six GpSGHV-encoded miRNAs were identified, of which five of
      them were only in symptomatic flies. These virus-encoded miRNAs may not only
      target host immune genes but may also participate in viral immune evasion. This
      evidence of differential host miRNA profile in Glossina in symptomatic flies
      advances our understanding of the GpSGHV-Glossina interactions and provides
      potential new avenues, for instance by utilization of particular miRNA inhibitors
      or mimics to better manage GpSGHV infections in tsetse mass-rearing facilities, a
      prerequisite for successful SIT implementation.

PMID- 30233522
TI  - Global Profiling of Lysine Acetylation in Borrelia burgdorferi B31 Reveals Its
      Role in Central Metabolism.
AB  - The post-translational modification of proteins has been shown to be extremely
      important in prokaryotes. Using a highly sensitive mass spectrometry-based
      proteomics approach, we have characterized the acetylome of B. burgdorferi. As
      previously reported for other bacteria, a relatively low number (5%) of the
      potential genome-encoded proteins of B. burgdorferi were acetylated. Of these,
      the vast majority were involved in central metabolism and cellular information
      processing (transcription, translation, etc.). Interestingly, these critical cell
      functions were targeted during both ML (mid-log) and S (stationary) phases of
      growth. However, acetylation of target proteins in ML phase was limited to single
      lysine residues while these same proteins were acetylated at multiple sites
      during S phase. To determine the acetyl donor in B. burgdorferi, we used mutants
      that targeted the sole acetate metabolic/anabolic pathway in B. burgdorferi
      (lipid I synthesis). B. burgdorferi strains B31-A3, B31-A3 DeltaackA (acetyl-P-
      and acetyl-CoA-) and B31-A3 Deltapta (acetyl-P+ and acetyl-CoA-) were grown to S
      phase and the acetylation profiles were analyzed. While only two proteins were
      acetylated in the DeltaackA mutant, 140 proteins were acetylated in the Deltapta
      mutant suggesting that acetyl-P was the primary acetyl donor in B. burgdorferi.
      Using specific enzymatic assays, we were able to demonstrate that
      hyperacetylation of proteins in S phase appeared to play a role in decreasing the
      enzymatic activity of at least two glycolytic proteins. Currently, we hypothesize
      that acetylation is used to modulate enzyme activities during different stages of
      growth. This strategy would allow the bacteria to post-translationally stimulate
      the activity of key glycolytic enzymes by deacetylation rather than expending
      excessive energy synthesizing new proteins. This would be an appealing, low
      energy strategy for a bacterium with limited metabolic capabilities. Future work
      focuses on identifying potential protein deacetylase(s) to complete our
      understanding of this important biological process.

PMID- 30233524
TI  - Single-Cell Genomics Reveals a Diverse Metabolic Potential of Uncultivated
      Desulfatiglans-Related Deltaproteobacteria Widely Distributed in Marine Sediment.
AB  - Desulfatiglans-related organisms comprise one of the most abundant
      deltaproteobacterial lineages in marine sediments where they occur throughout the
      sediment column in a gradient of increasing sulfate and organic carbon limitation
      with depth. Characterized Desulfatiglans isolates are dissimilatory sulfate
      reducers able to grow by degrading aromatic hydrocarbons. The ecophysiology of
      environmental Desulfatiglans-populations is poorly understood, however, possibly
      utilization of aromatic compounds may explain their predominance in marine
      subsurface sediments. We sequenced and analyzed seven Desulfatiglans-related
      single-cell genomes (SAGs) from Aarhus Bay sediments to characterize their
      metabolic potential with regard to aromatic compound degradation and energy
      metabolism. The average genome assembly size was 1.3 Mbp and completeness
      estimates ranged between 20 and 50%. Five of the SAGs (group 1) originated from
      the sulfate-rich surface part of the sediment while two (group 2) originated from
      sulfate-depleted subsurface sediment. Based on 16S rRNA gene amplicon sequencing
      group 2 SAGs represent the more frequent types of Desulfatiglans-populations in
      Aarhus Bay sediments. Genes indicative of aromatic compound degradation could be
      identified in both groups, but the two groups were metabolically distinct with
      regard to energy conservation. Group 1 SAGs carry a full set of genes for
      dissimilatory sulfate reduction, whereas the group 2 SAGs lacked any genetic
      evidence for sulfate reduction. The latter may be due to incompleteness of the
      SAGs, but as alternative energy metabolisms group 2 SAGs carry the genetic
      potential for growth by acetogenesis and fermentation. Group 1 SAGs encoded
      reductive dehalogenase genes, allowing them to access organohalides and possibly
      conserve energy by their reduction. Both groups possess sulfatases unlike their
      cultured relatives allowing them to utilize sulfate esters as source of organic
      carbon and sulfate. In conclusion, the uncultivated marine Desulfatiglans
      populations are metabolically diverse, likely reflecting different strategies for
      coping with energy and sulfate limitation in the subsurface seabed.

PMID- 30233525
TI  - Active Crossfire Between Cyanobacteria and Cyanophages in Phototrophic Mat
      Communities Within Hot Springs.
AB  - Cyanophages are viruses with a wide distribution in aquatic ecosystems, that
      specifically infect Cyanobacteria. These viruses can be readily isolated from
      marine and fresh waters environments; however, their presence in cosmopolitan
      thermophilic phototrophic mats remains largely unknown. This study investigates
      the morphological diversity (TEM), taxonomic composition (metagenomics), and
      active infectivity (metatranscriptomics) of viral communities over a thermal
      gradient in hot spring phototrophic mats from Northern Patagonia (Chile). The
      mats were dominated (up to 53%) by cosmopolitan thermophilic filamentous true
      branching cyanobacteria from the genus Mastigocladus, the associated viral
      community was predominantly composed of Caudovirales (70%), with most of the
      active infections driven by cyanophages (up to 90% of Caudovirales transcripts).
      Metagenomic assembly lead to the first full genome description of a T7-like
      Thermophilic Cyanophage recovered from a hot spring (Porcelana Hot Spring,
      Chile), with a temperature of 58 degrees C (TC-CHP58). This could potentially
      represent a world-wide thermophilic lineage of podoviruses that infect
      cyanobacteria. In the hot spring, TC-CHP58 was active over a temperature gradient
      from 48 to 66 degrees C, showing a high population variability represented by
      1979 single nucleotide variants (SNVs). TC-CHP58 was associated to the
      Mastigocladus spp. by CRISPR spacers. Marked differences in metagenomic CRISPR
      loci number and spacers diversity, as well as SNVs, in the TC-CHP58 proto-spacers
      at different temperatures, reinforce the theory of co-evolution between natural
      virus populations and cyanobacterial hosts. Considering the importance of
      cyanobacteria in hot spring biogeochemical cycles, the description of this new
      cyanopodovirus lineage may have global implications for the functioning of these
      extreme ecosystems.

PMID- 30233527
TI  - Characterization of Pediococcus ethanolidurans CUPV141: A beta-D-glucan- and
      Heteropolysaccharide-Producing Bacterium.
AB  - Pediococcus ethanolidurans CUPV141 is an exopolysaccharide (EPS)-producing lactic
      acid bacterium, first isolated from Basque Country cider (Spain). Physicochemical
      analysis of the EPS synthesized by the bacterium revealed that CUPV141 produces
      mostly a homopolysaccharide (HoPS), characterized as a 2-substituted (1,3)-beta-D
      glucan, together with a small quantity of a heteropolysaccharide (HePS) composed
      of glucose, galactose, glucosamine, and glycerol-3-phosphate, this being the
      first Pediococcus strain described to produce this kind of polymer. On the
      contrary, an isogenic strain CUPV141NR, generated by chemical mutagenesis of
      CUPV141, produced the HePS as the main extracellular polysaccharide and a barely
      detectable amount of 2-substituted (1,3)-beta-D-glucan. This HoPS is synthesized
      by the transmembrane GTF glycosyltransferase (GTF), encoded by the gtf gene,
      which has been previously reported to be located in the pPP2 plasmid of the
      Pediococcus parvulus 2.6 strain. Southern blot hybridization revealed that in
      CUPV141 the gtf gene is located in a plasmid designated as pPE3, whose molecular
      mass (34.4 kbp) is different from that of pPP2 (24.5 kbp). Analysis of the
      influence of the EPS on the ability of the producing bacteria to adhere to the
      eukaryotic Caco-2 cells revealed higher affinity for the human enterocytes of
      CUPV141NR compared to that of CUPV141. This result indicates that, in contrast to
      the 2.6 strain, the presence of the HoPS does not potentiate the binding ability
      of P. ethanolidurans. Moreover, it supports that the phosphate-containing
      bacterial HePS improved the interaction between P. ethanolidurans and the
      eukaryotic cells.

PMID- 30233526
TI  - Multi-Year Persistence of Verotoxigenic Escherichia coli (VTEC) in a Closed
      Canadian Beef Herd: A Cohort Study.
AB  - In this study, fecal samples were collected from a closed beef herd in Alberta,
      Canada from 2012 to 2015. To limit serotype bias, which was observed in
      enrichment broth cultures, Verotoxigenic Escherichia coli (VTEC) were isolated
      directly from samples using a hydrophobic grid-membrane filter verotoxin
      immunoblot assay. Overall VTEC isolation rates were similar for three different
      cohorts of yearling heifers on both an annual (68.5 to 71.8%) and seasonal basis
      (67.3 to 76.0%). Across all three cohorts, O139:H19 (37.1% of VTEC-positive
      samples), O22:H8 (15.8%) and O?(O108):H8 (15.4%) were among the most prevalent
      serotypes. However, isolation rates for serotypes O139:H19, O130:H38, O6:H34,
      O91:H21, and O113:H21 differed significantly between cohort-years, as did
      isolation rates for some serotypes within a single heifer cohort. There was a
      high level of VTEC serotype diversity with an average of 4.3 serotypes isolated
      per heifer and 65.8% of the heifers classified as "persistent shedders" of VTEC
      based on the criteria of >50% of samples positive and >=4 consecutive samples
      positive. Only 26.8% (90/336) of the VTEC isolates from yearling heifers belonged
      to the human disease-associated seropathotypes A (O157:H7), B (O26:H11, O111:NM),
      and C (O22:H8, O91:H21, O113:H21, O137:H41, O2:H6). Conversely, seropathotypes B
      (O26:NM, O111:NM) and C (O91:H21, O2:H29) strains were dominant (76.0%, 19/25)
      among VTEC isolates from month-old calves from this herd. Among VTEC from
      heifers, carriage rates of vt1, vt2, vt1+vt2, eae, and hlyA were 10.7, 20.8,
      68.5, 3.9, and 88.7%, respectively. The adhesin gene saa was present in 82.7% of
      heifer strains but absent from all of 13 eae+ve strains (from serotypes/intimin
      types O157:H7/gamma1, O26:H11/beta1, O111:NM/theta, O84:H2/zeta, and
      O182:H25/zeta). Phylogenetic relationships inferred from wgMLST and pan genome
      derived core SNP analysis showed that strains clustered by phylotype and
      serotype. Further, VTEC strains of the same serotype usually shared the same
      suite of antibiotic resistance and virulence genes, suggesting the circulation of
      dominant clones within this distinct herd. This study provides insight into the
      diverse and dynamic nature of VTEC populations within groups of cattle and points
      to a broad spectrum of human health risks associated with these E. coli strains.

PMID- 30233528
TI  - Protists Within Corals: The Hidden Diversity.
AB  - Previous observations suggested that microbial communities contribute to coral
      health and the ecological resilience of coral reefs. However, most studies of
      coral microbiology focused on prokaryotes and the endosymbiotic algae
      Symbiodinium. In contrast, knowledge concerning diversity of other protists is
      still lacking, possibly due to methodological constraints. As most eukaryotic DNA
      in coral samples was derived from hosts, protist diversity was missed in
      metagenome analyses. To tackle this issue, we designed blocking primers for
      Scleractinia sequences amplified with two primer sets that targeted variable
      loops of the 18S rRNA gene (18SV1V2 and 18SV4). These blocking primers were used
      on environmental colonies of Pocillopora damicornis sensu lato from two regions
      with contrasting thermal regimes (Djibouti and New Caledonia). In addition to
      Symbiodinium clades A/C/D, Licnophora and unidentified coccidia genera were found
      in many samples. In particular, coccidian sequences formed a robust monophyletic
      clade with other protists identified in Agaricia, Favia, Montastraea,
      Mycetophyllia, Porites, and Siderastrea coral colonies. Moreover, Licnophora and
      coccidians had different distributions between the two geographic regions. A
      similar pattern was observed between Symbiodinium clades C and A/D. Although we
      were unable to identify factors responsible for this pattern, nor were we able to
      confirm that these taxa were closely associated with corals, we believe that
      these primer sets and the associated blocking primers offer new possibilities to
      describe the hidden diversity of protists within different coral species.

PMID- 30233530
TI  - Design of Primers for Evaluation of Lactic Acid Bacteria Populations in Complex
      Biological Samples.
AB  - Lactic acid bacteria (LAB) are important for human health. However, the relative
      abundance of LAB in complex samples, such as fecal samples, is low and their
      presence and diversity (at the species level) is understudied. Therefore, we
      designed LAB-specific primer pairs based on 16S rRNA gene consensus sequences
      from 443 species of LAB from seven genera. The LAB strains selected were
      genetically similar and known to play a role in human health. Prior to primer
      design, we obtained consistent sequences for the primer-binding sites by
      comparing the 16S rRNA gene sequences, manually identifying single-stranded
      primers and modifying these primers using degenerate bases. We assembled primer
      pairs with product sizes of >400 bp. Optimal LAB-specific primers were screened
      using three methods: PCR amplification, agarose gel electrophoresis and single
      molecule real-time (SMRT) sequencing analysis. During the SMRT analysis
      procedure, we focused on sequence reads and diversity at the species level of
      target LAB in three fecal samples, using the universal bacterium primer 27f/1492r
      as a reference control. We created a phylogenetic tree to confirm the ability of
      the best candidate primer pair to differentiate amongst species. The results
      revealed that LAB-specific primer L5, with a product size of 750 bp, could
      generate 3222, 2552, and 3405 sequence reads from fecal Samples 1, 2, and 3. This
      represented 14, 13 and 10% of all target LAB sequence reads, respectively,
      compared with 2, 0.8, and 0.8% using the 27f/1492r primer. In addition, L5
      detected LAB that were in low abundance and could not be detected using the
      27f/1492r primer. The phylogenetic tree based on the alignments between the
      forward and reverse primer of L5 showed that species within the seven target LAB
      genera could be distinguished from each other, confirming L5 is a powerful tool
      for inferring phylogenetic relationships amongst LAB species. In conclusion, L5
      is a LAB-specific primer that can be used for high-throughput sequencing and
      identification of taxa to the species level, especially in complex samples with
      relatively low LAB content. This enables further research on LAB population
      diversity in complex ecosystem, and on relationships between LAB and their hosts.

PMID- 30233529
TI  - Characterizing Mobilized Virulence Factors and Multidrug Resistance Genes in
      Carbapenemase-Producing Klebsiella pneumoniae in a Sri Lankan Hospital.
AB  - Limited data is available on the epidemiology and characteristics of carbapenem
      resistant Enterobacteriaceae (CRE) and their associated plasmids or virulence
      determinants from Sri Lanka. Through whole genome sequencing of CREs from the
      intensive care units of a Sri Lankan teaching hospital, we identified a
      carbapenemase gene, blaOXA-181 in 10 carbapenemase-producing Klebsiella
      pneumoniae isolates (two strains of ST437 and eight strains of ST147) from 379
      respiratory specimens. blaOXA-181 was carried in three variants of ColE-type
      plasmids. K. pneumoniae strains with ompK36 variants showed high minimum
      inhibitory concentrations to carbapenem. Furthermore, genes encoding for extended
      spectrum beta-lactamases (ESBL), plasmid-mediated quinolone resistance (PMQR)
      determinants (qnr, aac(6')-Ib-cr, and oqxAB) were present in all 10 strains.
      Amino acid substitution in chromosomal quinolone resistance-determining regions
      (QRDRs) gyrA (Ser83Ile) and parC (Ser80Ile) were also observed. All strains had
      yersiniabactin genes on mobile element ICEkp. Strict infection control practices
      and judicious use of antibiotics are warranted to prevent further spread of
      multidrug-resistant K. pneumoniae.

PMID- 30233531
TI  - Screening for Lactobacillus plantarum Strains That Possess Organophosphorus
      Pesticide-Degrading Activity and Metabolomic Analysis of Phorate Degradation.
AB  - This work performed a large scale assessment for organophosphorus pesticides
      (OPPs) degradation activity of 121 Lactobacillus (L.) plantarum strains. Six L.
      plantarum strains (P9, IMAU80110, IMAU40100, IMAU10585, IMAU10209, and IMAU80070)
      were found to possess high capacity of degrading three commonly used OPPs, namely
      dimethoate, phorate, and omethoate; and they were selected for more detailed
      characterization. Moreover, the three OPPs were mainly detected in the culture
      supernatants but not in the cell extracts, further confirming that the OPPs were
      degraded rather than absorbed by the cells. Among the six selected strains, P9
      was most tolerant to gastrointestinal juices and bile. We thus used ultra-high
      performance liquid chromatography electron spray ionization coupled with time-of
      flight mass spectrometry (UPLC/ESI-Q-TOF/MS) to generate the metabolomic profiles
      of the strain P9 growing in MRS medium with and without containing phorate. By
      using orthogonal partial least squares discriminant analysis, we identified some
      potential phorate-derived degradative products. This work has identified novel
      lactic acid bacteria resources for application in pesticide degradation. Our
      results also shed light on the phorate degradation mechanism by L. plantarum P9.

PMID- 30233532
TI  - Listeria monocytogenes Response to Sublethal Chlorine Induced Oxidative Stress on
      Homologous and Heterologous Stress Adaptation.
AB  - The objective of this study was to determine the effect of chlorine induced
      sublethal oxidative stress against homologous and heterologous stress adaptations
      in five Listeria monocytogenes (Lm) strains. Lm cells were exposed to gradually
      increasing sublethal concentrations of total chlorine/day: 250 ppm (day 1), 270
      ppm (day 2), 290 ppm (day 3), 310 ppm (day 4), 330 ppm (day 5), 350 ppm (day 6),
      and 375 ppm (day 7) in tryptic soy broth (TSB). Changes in minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) of Lm cells
      exposed to chlorine and control (non-adapted cells) were determined by the macro
      dilution method. Chlorine-adapted Lm cells were also evaluated for changes in
      antibiotic resistance using the Kirby-Bauer disk diffusion and MIC double
      dilution assay as per the Clinical and Laboratory Standards Institute (CLSI,
      2016) guidelines. In four Lm strains (Scott A, V7, FSL-N1-227 and FSL-F6-154)
      after adapted to sublethal chlorine, the MIC (600 ppm) and MBC (700 ppm) values
      of chlorine were slightly higher as compared to control (500 ppm MIC, and 600 ppm
      MBC). The Kirby-Bauer and MIC double dilution assays showed some significant
      changes in antibiotic susceptibility patterns for antibiotics such as
      streptomycin, gentamicin and ceftriaxone (p < 0.05). However, the changes in
      zones of inhibition and MIC values to all antibiotics tested for the chlorine
      adapted and non-adapted (control) Lm cells were still within the susceptible
      range. Transmission electron microscopy studies showed that changes in cell wall
      and membrane integrity resulting, from the elongation of cells, may contribute to
      the possible routes of its increase in tolerance to chlorine and selective
      antibiotics. These findings indicate that the continuous exposure of Lm cells to
      chlorine may lead to significant changes in homologs and heterologous stress
      adaptation.

PMID- 30233533
TI  - Is Phosphate Solubilization the Forgotten Child of Plant Growth-Promoting
      Rhizobacteria?

PMID- 30233534
TI  - 1-Methyltryptophan Modifies Apoplast Content in Tomato Plants Improving
      Resistance Against Pseudomonas syringae.
AB  - Plants can produce numerous natural products, many of which have been shown to
      confer protection against microbial attack. In this way, we identified 1
      methyltryptophan (1-MT), a natural compound produced by tomato plants in response
      to Pseudomonas syringae attack, whose application by soil drench provided
      protection against this pathogen. In the present work, we have studied the
      mechanisms underlying this protection. The results demonstrated that 1-MT can be
      considered a new activator of plant defense responses that acts by inhibiting the
      stomatal opening produced by coronatine (COR) and could thereby, prevent bacteria
      entering the mesophyll. Besides, 1-MT acts by blocking the jasmonic acid (JA)
      pathway that, could avoid manipulation of the salicylic acid (SA) pathway by the
      bacterium, and thus hinder its growth. Although the concentration of 1-MT reached
      in the plant did not show antimicrobial effects, we cannot rule out a role for 1
      MT acting alone because it affects the expression of the fliC gene that is
      involved in synthesis of the flagellum. These changes would result in reduced
      bacterium motility and, therefore, infective capacity. The results highlight the
      effect of a tryptophan derivative on induced resistance in plants.

PMID- 30233535
TI  - Spread of Carbapenem Resistance by Transposition and Conjugation Among
      Pseudomonas aeruginosa.
AB  - The emergence of carbapenem-resistant Pseudomonas aeruginosa represents a
      worldwide problem. To understand the carbapenem-resistance mechanisms and their
      spreading among P. aeruginosa strains, whole genome sequences were determined of
      two extensively drug-resistant strains that are endemic in Dutch hospitals.
      Strain Carb01 63 is of O-antigen serotype O12 and of sequence type ST111, whilst
      S04 90 is a serotype O11 strain of ST446. Both strains carry a gene for metallo
      beta-lactamase VIM-2 flanked by two aacA29 genes encoding aminoglycoside
      acetyltransferases on a class 1 integron. The integron is located on the
      chromosome in strain Carb01 63 and on a plasmid in strain S04 90. The backbone of
      the 159-kb plasmid, designated pS04 90, is similar to a previously described
      plasmid, pND6-2, from Pseudomonas putida. Analysis of the context of the integron
      showed that it is present in both strains on a ~30-kb mosaic DNA segment composed
      of four different transposons that can presumably act together as a novel,
      active, composite transposon. Apart from the presence of a 1237-bp insertion
      sequence element in the composite transposon on pS04 90, these transposons show >
      99% sequence identity indicating that transposition between plasmid and
      chromosome could have occurred only very recently. The pS04 90 plasmid could be
      transferred by conjugation to a susceptible P. aeruginosa strain. A second class
      1 integron containing a gene for a CARB-2 beta-lactamase flanked by an aacA4'-8
      and an aadA2 gene, encoding an aminoglycoside acetyltransferase and
      adenylyltransferase, respectively, was present only in strain Carb01 63. This
      integron is located also on a composite transposon that is inserted in an
      integrative and conjugative element on the chromosome. Additionally, this strain
      contains a frameshift mutation in the oprD gene encoding a porin involved in the
      transport of carbapenems across the outer membrane. Together, the results
      demonstrate that integron-encoded carbapenem and carbapenicillin resistance can
      easily be disseminated by transposition and conjugation among Pseudomonas
      aeruginosa strains.

PMID- 30233536
TI  - Dietary Probiotic Effect of Lactococcus lactis WFLU12 on Low-Molecular-Weight
      Metabolites and Growth of Olive Flounder (Paralichythys olivaceus).
AB  - The use of probiotics is considered an attractive biocontrol method. It is
      effective in growth promotion in aquaculture. However, the mode of action of
      probiotics in fish in terms of growth promotion remains unclear. The objective of
      the present study was to investigate growth promotion effect of dietary
      administration of host-derived probiotics, Lactococcus lactis WFLU12, on olive
      flounder compared to control group fed with basal diet by analyzing their
      intestinal and serum metabolome using capillary electrophoresis mass spectrometry
      with time-of flight (CE-TOFMS). Results of CE-TOFMS revealed that 53 out of 200
      metabolites from intestinal luminal metabolome and 5 out of 171 metabolites from
      serum metabolome, respectively, were present in significantly higher
      concentrations in the probiotic-fed group than those in the control group.
      Concentrations of metabolites such as citrulline, tricarboxylic acid cycle (TCA)
      intermediates, short chain fatty acids, vitamins, and taurine were significantly
      higher in the probiotic-fed group than those in the control group. The probiotic
      strain WFLU12 also possesses genes encoding enzymes to help produce these
      metabolites. Therefore, it is highly likely that these increased metabolites
      linked to growth promotion in olive flounder are due to supplementation of the
      probiotic strain. To the best of our knowledge, this is the first study to show
      that dietary probiotics can greatly influence metabolome in fish. Findings of the
      present study may reveal important implications for maximizing the efficiency of
      using dietary additives to optimize fish health and growth.

PMID- 30233537
TI  - Local Functioning, Landscape Structuring: Drivers of Soil Microbial Community
      Structure and Function in Peatlands.
AB  - Agricultural peatlands are essential for a myriad of ecosystem functions and play
      an important role in the global carbon (C) cycle through C sequestration.
      Management of these agricultural peatlands takes place at different spatial
      scales, ranging from local to landscape management, and drivers of soil microbial
      community structure and function may be scale-dependent. Effective management for
      an optimal biogeochemical functioning thus requires knowledge of the drivers on
      soil microbial community structure and functioning, as well as the spatial scales
      upon which they are influenced. During two field campaigns, we examined the
      importance of different drivers (i.e., soil characteristics, nutrient management,
      vegetation composition) at two spatial scales (local vs. landscape) for,
      respectively, the soil microbial community structure (determined by PLFA) and
      soil microbial community functional capacity (as assessed by CLPP) in
      agricultural peatlands. First, we show by an analysis of PLFA profiles that the
      total microbial biomass changes with soil moisture and relative C:P nutrient
      availability. Secondly, we showed that soil communities are controlled by a
      distinct set of drivers at the local, as opposed to landscape, scale. Community
      structure was found to be markedly different between areas, in contrast to
      community function which showed high variability within areas. We further found
      that microbial structure appears to be controlled more at a landscape scale by
      nutrient-related variables, whereas microbial functional capacity is driven
      locally through plant community feedbacks. Optimal management strategies within
      such peatlands should therefore consider the scale-dependent action of soil
      microbial community drivers, for example by first optimizing microbial structure
      at the landscape scale by targeted areal management, and then optimizing soil
      microbial function by local vegetation management.

PMID- 30233538
TI  - The Genomic Potentials of NOB and Comammox Nitrospira in River Sediment Are
      Impacted by Native Freshwater Mussels.
AB  - Freshwater mussel assemblages of the Upper Mississippi River (UMR) sequester tons
      of ammonia- and urea-based biodeposits each day and aerate sediment through
      burrowing activities, thus creating a unique niche for nitrogen (N) cycling
      microorganisms. This study explored how mussels impact the abundance of N-cycling
      species with an emphasis on Candidatus Nitrospira inopinata, the first
      microorganism known to completely oxidize ammonia (comammox) to nitrate. This
      study used metagenomic shotgun sequencing of genomic DNA to compare nitrogen
      cycling species in sediment under a well-established mussel assemblage and in
      nearby sediment without mussels. Metagenomic reads were aligned to the
      prokaryotic RefSeq non-redundant protein database using BLASTx, taxonomic binning
      was performed using the weighted lowest common ancestor algorithm, and protein
      coding genes were categorized by metabolic function using the SEED subsystem.
      Linear discriminant analysis (LDA) effect sizes were used to determine which
      metagenomes and metabolic features explained the most differences between the
      mussel habitat sediment and sediment without mussels. Of the N-cycling species
      deemed differentially abundant, Nitrospira moscoviensis and "Candidatus
      Nitrospira inopinata" were responsible for creating a distinctive N-cycling
      microbiome in the mussel habitat sediment. Further investigation revealed that
      comammox Nitrospira had a large metabolic potential to degrade mussel
      biodeposits, as evidenced the top ten percent of protein-coding genes including
      the cytochrome c-type biogenesis protein required for hydroxylamine oxidation,
      ammonia monooxygenase, and urea decomposition SEED subsystems. Genetic marker
      analysis of these two Nitrospira taxons suggested that N. moscoviensis was most
      impacted by diverse carbon metabolic processes while "Candidatus Nitrospira
      inopinata" was most distinguished by multidrug efflux proteins (AcrB), NiFe
      hydrogenase (HypF) used in hydrogen oxidation and sulfur reduction coupled
      reactions, and a heme chaperone (CcmE). Furthermore, our research suggests that
      comammox and NOB Nitrospira likely coexisted by utilizing mixotrophic
      metabolisms. For example, "Candidatus Nitrospira inopinata" had the largest
      potentials for ammonia oxidation, nitrite reduction with NirK, and hydrogen
      oxidation, while NOB Nitrospira had the greatest potential for nitrite oxidation,
      and nitrate reduction possibly coupled with formate oxidation. Overall, our
      results suggest that this mussel habitat sediment harbors a niche for NOB and
      comammox Nitrospira, and ultimately impacts N-cycling in backwaters of the UMR.

PMID- 30233539
TI  - Influence of Altered Microbes on Soil Organic Carbon Availability in Karst
      Agricultural Soils Contaminated by Pb-Zn Tailings.
AB  - Soil organic carbon (SOC) availability is determined via a complex bio-mediated
      process, and Pb-Zn tailings are toxic to the soil microbes that are involved in
      this process. Here, Pb-Zn-tailings- contaminated karst soils with different
      levels (paddy field > corn field > citrus field > control group) were collected
      to explore the intrinsic relationship between Pb-Zn tailings and microbes due to
      the limited microbial abundance in these soils. The SOC concentration in the
      paddy fields is the highest. However, based on the soil microbial diversity and
      sole-carbon-source utilization profiles, the rate of SOC availability, McIntosh
      index, Shannon-Wiener diversity index, Simpson's diversity index and species
      richness are the lowest in the rice paddy soils. According to the results of
      Illumina sequencing of the 16S rRNA gene, Acidobacteria and Proteobacteria are
      the dominant phyla in all samples, accounting for more than 70% of the reads,
      while the majority of the remaining reads belong to the phyla Verrucomicrobia,
      Chloroflexi, Actinobacteria, Bacteroidetes, and Nitrospirae. We also observed
      that their class, order, family, genus and operational taxonomic units (OTUs)
      were dependent on SOC availability. Pearson correlation analysis reveals that L
      asparagine utilization profiles show significant positive correlation with OTUs
      24, 75, and 109 (r = 0.383, 0.350, and 0.292, respectively), and malic acid
      utilization profiles show significant positive correlation with OTUs 4, 5, 19, 27
      (Bradyrhizobium), 32 (Burkholderia), 75 and 109 (r = 0.286, 0.361, 0.387, 0.384,
      0.363, 0.285, and 0.301, respectively), as also evidenced by the redundancy
      analysis (RDA) biplot and heat map. These results indicate that the most abundant
      groups of bacteria, especially the uncultured facultative Deltaproteobacteria GR
      WP33-30 (OTU 24), after long-term acclimation in heavy metal-contaminated soil,
      are associated with the variance of labile carbon source such as L-asparagine and
      may have considerable control over the stability of the vast SOC pool in karst
      surface soils with different agricultural land-use practices. These findings can
      expand our understanding of global soil-carbon sequestration and storage via
      changes in microbial community structure of the most abundant species.

PMID- 30233541
TI  - RiCRN1, a Crinkler Effector From the Arbuscular Mycorrhizal Fungus Rhizophagus
      irregularis, Functions in Arbuscule Development.
AB  - Arbuscular mycorrhizal (AM) symbiosis is one of the most prominent and beneficial
      plant-microbe interactions that facilitates mineral nutrition and confers
      tolerance to biotic and abiotic stresses. AM fungi colonize the root cortex and
      develop specialized structures called arbuscules where the nutrient exchange
      takes place. Arbuscule development is a highly controlled and coordinated process
      requiring the involvement of many plant proteins recruited at that interface. In
      contrast, much less is known about the fungal proteins involved in this process.
      Here, we have identified an AM fungal effector that participates in this
      developmental step of the symbiosis. RiCRN1 is a crinkler (CRN) effector that
      belongs to a subfamily of secreted CRN proteins from R. irregularis. CRNs have
      been so far only functionally characterized in pathogenic microbes and shown to
      participate in processes controlling plant cell death and immunity. RiCRN1
      accumulates during symbiosis establishment parallel to MtPT4, the gene coding for
      an arbuscule-specific phosphate transporter. Expression in Nicotiana benthamiana
      leaves and in Medicago truncatula roots suggest that RiCRN1 is not involved in
      cell death processes. RiCRN1 dimerizes and localizes to nuclear bodies,
      suggesting that, similar to other CRNs, it functions in the plant nucleus.
      Downregulation of RiCRN1 using host-induced gene silencing led to an impairment
      of the symbiosis in M. truncatula and to a reduction of MtPT4, while ectopic
      expression of RiCRN1, surprisingly, led to a drastic reduction in arbuscule size
      that correlated with a decrease not only in MtPT4 but also in MtBCP1, a marker
      for initial stages of arbuscule development. Altogether, our results suggest that
      a tightly regulated expression in time and space of RiCRN1 is critical for
      symbiosis progression and for the proper initiation of arbuscule development.

PMID- 30233540
TI  - Bacterial Strategies to Preserve Cell Wall Integrity Against Environmental
      Threats.
AB  - Bacterial cells are surrounded by an exoskeleton-like structure, the cell wall,
      composed primarily of the peptidoglycan (PG) sacculus. This structure is made up
      of glycan strands cross-linked by short peptides generating a covalent mesh that
      shapes bacteria and prevents their lysis due to their high internal osmotic
      pressure. Even though the PG is virtually universal in bacteria, there is a
      notable degree of diversity in its chemical structure. Modifications in both the
      sugars and peptides are known to be instrumental for bacteria to cope with
      diverse environmental challenges. In this review, we summarize and discuss the
      cell wall strategies to withstand biotic and abiotic environmental insults such
      as the effect of antibiotics targeting cell wall enzymes, predatory PG hydrolytic
      proteins, and PG signaling systems. Finally we will discuss the opportunities
      that species-specific PG variability might open to develop antimicrobial
      therapies.

PMID- 30233543
TI  - Transfusion-Associated Lyme Disease - Although Unlikely, It Is Still a Concern
      Worth Considering.
AB  - Even though hematogenous spread of the Lyme disease spirochete, Borrelia
      burgdorferi, has been well documented, and there are more than 300,000 cases per
      year of Lyme disease in the United States, no evidence (anecdotal or published)
      of transfusion-associated Lyme disease has been reported. Such a possibility
      would seem to exist but various factors, as discussed in this perspective, make
      this less likely to occur. Nonetheless, if not done already, safeguards need to
      be put in place at blood collection and dispensing facilities, possibly with the
      assistance of diagnostic microbiology and immunology laboratories, to ensure that
      the potential for the transfer of the Lyme disease spirochete through a blood
      transfusion remains a theoretical consideration rather than a real possibility.

PMID- 30233542
TI  - Development of a Colloidal Gold-Based Immunochromatographic Strip for Rapid
      Detection of H7N9 Influenza Viruses.
AB  - Both high- and low-pathogenic H7N9 influenza A virus (IAV) infections have been
      found in human and poultry in China, and most human cases are related to contact
      with infected poultry. It is necessary to develop a rapid and simple method to
      detect H7N9 IAV in poultry. In this study, 13 monoclonal antibodies (McAbs)
      against the H7N9 IAV hemagglutinin were developed, and three critical amino acid
      epitopes (198, 227, 235) were identified based on the reactivity of these variant
      and wild-type strains with the McAbs. We developed an immunochromatographic assay
      for H7N9 AIVs using two McAbs recognizing the epitope position 227 and 235. The
      assay had good specificity, stability, and sensitivity, with a detection limit of
      swab and tissue samples of 2.5 log10EID50/0.1 mL, which is suitable for the
      analysis of clinical samples. This assay provides an effective method for the
      rapid detection of H7N9 AIVs in poultry.

PMID- 30233544
TI  - Shigellaflexneri Regulator SlyA Controls Bacterial Acid Resistance by Directly
      Activating the Glutamate Decarboxylation System.
AB  - Shigella flexneri is an important foodborne bacterial pathogen with infectious
      dose as low as 10-100 cells. SlyA, a transcriptional regulator of the MarR
      family, has been shown to regulate virulence in a closely related bacterial
      pathogen, Salmonella Typhimurium. However, the regulatory role of SlyA in S.
      flexneri is less understood. Here we applied unbiased proteomic profiling to
      define the SlyA regulon in S. flexneri. We found that the genetic ablation of
      slyA led to the alteration of 18 bacterial proteins among over 1400
      identifications. Intriguingly, most down-regulated proteins (whose expression is
      SlyA-dependent) were associated with bacterial acid resistance such as the
      glutamate decarboxylation system. We further demonstrated that SlyA directly
      regulates the expression of GadA, a glutamate decarboxylase, by binding to the
      promotor region of its coding gene. Importantly, overexpression of GadA was able
      to rescue the survival defect of the DeltaslyA mutant under acid stress.
      Therefore, our study highlights a major role of SlyA in controlling S. flexneri
      acid resistance and provides a molecular mechanism underlying such regulation as
      well.

PMID- 30233545
TI  - A Ready-to-Use Single- and Duplex-TaqMan-qPCR Assay to Detect and Quantify the
      Biocontrol Agents Trichoderma asperellum and Trichoderma gamsii.
AB  - Trichoderma asperellum strain icc012 and Trichoderma gamsii strain icc080, the
      microbial active ingredients of RemedierTM (ISAGRO, Novara, Italy), are
      biocontrol agents (BCAs) employable for crop protection against a wide range of
      fungal pathogens, including soil-borne pathogens and fungi involved in grapevine
      trunk disease. In this study, single and duplex real-time quantitative PCR (qPCR)
      methods to detect and quantify T. asperellum and T. gamsii were developed.
      Primers/probe sets were designed on the T. asperellum and T. gamsii rpb2 genes
      and tested for specificity on a panel of microorganisms commonly associated with
      grape wood and soil. No differences were observed comparing single- and duplex
      qPCR assays on different BCAs, 1 pg of target DNA was detected approximately at
      Cq = 34. R2-values and the efficiency were always equal to 0.99 and >80%,
      respectively. The detection limit of the duplex-qPCR assay on artificially
      inoculated samples was 2 * 103 and 4 * 104 conidia g-1 of grape wood tissue and
      soil, respectively. The methods will be useful to better schedule BCA application
      in the field and in grapevine nurseries, as well as for investigating the dynamic
      of BCA populations.

PMID- 30233546
TI  - Whole Transcriptome Sequencing Analysis of the Synergistic Antimicrobial Effect
      of Metal Oxide Nanoparticles and Ajoene on Campylobacter jejuni.
AB  - Two metal oxide (i.e., Al2O3 and TiO2) nanoparticles and ajoene, a garlic-derived
      organosulfur compound, were identified to be effective antimicrobials against
      Campylobacter jejuni, a leading cause of human gastrointestinal diseases
      worldwide. A significant synergistic antimicrobial effect was observed using
      ajoene and Al2O3/TiO2 nanoparticles in a combined manner to cause at least 8
      log10 CFU/mL reduction of C. jejuni cells. Whole transcriptome sequencing (RNA
      seq) and confocal micro-Raman spectroscopic analyses revealed the antimicrobial
      mechanism and identified the roles of ajoene and metal oxide nanoparticles in the
      synergistic treatment. Ajoene and metal oxide nanoparticles mediated a two-phase
      antimicrobial mechanism. Ajoene served as the inducing factor at the first phase
      that caused injury of cell membranes and increased the susceptibility of C.
      jejuni to stress. Metal oxide nanoparticles served as the active factor at the
      second phase that targeted sensitive cells and physically disrupted cell
      structure. This synergistic antimicrobial treatment demonstrates a potential to
      reduce the prevalence of C. jejuni and other pathogens on food contact surfaces
      and in the food chain.

PMID- 30233547
TI  - Revisiting the Taxonomy of the Genus Arcobacter: Getting Order From the Chaos.
AB  - Since the description of the genus Arcobacter in 1991, a total of 27 species have
      been described, although some species have shown 16S rRNA similarities below 95%,
      which is the cut-off that usually separates species that belong to different
      genera. The objective of the present study was to reassess the taxonomy of the
      genus Arcobacter using information derived from the core genome (286 genes), a
      Multilocus Sequence Analysis (MLSA) with 13 housekeeping genes, as well as
      different genomic indexes like Average Nucleotide Identity (ANI), in silico DNA
      DNA hybridization (isDDH), Average Amino-acid Identity (AAI), Percentage of
      Conserved Proteins (POCPs), and Relative Synonymous Codon Usage (RSCU). The study
      included a total of 39 strains that represent all the 27 species included in the
      genus Arcobacter together with 13 strains that are potentially new species, and
      the analysis of 57 genomes. The different phylogenetic analyses showed that the
      Arcobacter species grouped into four clusters. In addition, A. lekithochrous and
      the candidatus species 'A. aquaticus' appeared, as did A. nitrofigilis, the type
      species of the genus, in separate branches. Furthermore, the genomic indices ANI
      and isDDH not only confirmed that all the species were well-defined, but also the
      coherence of the clusters. The AAI and POCP values showed intra-cluster ranges
      above the respective cut-off values of 60% and 50% described for species
      belonging to the same genus. Phenotypic analysis showed that certain test
      combinations could allow the differentiation of the four clusters and the three
      orphan species established by the phylogenetic and genomic analyses. The origin
      of the strains showed that each of the clusters embraced species recovered from a
      common or related environment. The results obtained enable the division of the
      current genus Arcobacter in at least seven different genera, for which the names
      Arcobacter, Aliiarcobacter gen. nov., Pseudoarcobacter gen. nov., Haloarcobacter
      gen. nov., Malacobacter gen. nov., Poseidonibacter gen. nov., and Candidate
      'Arcomarinus' gen. nov. are proposed.

PMID- 30233548
TI  - An Engineered Synthetic Biologic Protects Against Clostridium difficile
      Infection.
AB  - Morbidity and mortality attributed to Clostridium difficile infection (CDI) have
      increased over the past 20 years. Currently, antibiotics are the only US FDA
      approved treatment for primary C. difficile infection, and these are, ironically,
      associated with disease relapse and the threat of burgeoning drug resistance. We
      previously showed that non-toxin virulence factors play key roles in CDI, and
      that colonization factors are critical for disease. Specifically, a C. difficile
      adhesin, Surface Layer Protein A (SlpA) is a major contributor to host cell
      attachment. In this work, we engineered Syn-LAB 2.0 and Syn-LAB 2.1, two
      synthetic biologic agents derived from lactic acid bacteria, to stably and
      constitutively express a host-cell binding fragment of the C. difficile adhesin
      SlpA on their cell-surface. Both agents harbor conditional suicide plasmids
      expressing a codon-optimized chimera of the lactic acid bacterium's cell-wall
      anchoring surface-protein domain, fused to the conserved, highly adherent, host
      cell-binding domain of C. difficile SlpA. Both agents also incorporate engineered
      biocontrol, obviating the need for any antibiotic selection. Syn-LAB 2.0 and Syn
      LAB 2.1 possess positive biophysical and in vivo properties compared with their
      parental antecedents in that they robustly and constitutively display the SlpA
      chimera on their cell surface, potentiate human intestinal epithelial barrier
      function in vitro, are safe, tolerable and palatable to Golden Syrian hamsters
      and neonatal piglets at high daily doses, and are detectable in animal feces
      within 24 h of dosing, confirming robust colonization. In combination, the
      engineered strains also delay (in fixed doses) or prevent (when continuously
      administered) death of infected hamsters upon challenge with high doses of
      virulent C. difficile. Finally, fixed-dose Syn-LAB ameliorates diarrhea in a non
      lethal model of neonatal piglet enteritis. Taken together, our findings suggest
      that the two synthetic biologics may be effectively employed as non-antibiotic
      interventions for CDI.

PMID- 30233549
TI  - Porphyromonas gingivalis Promotes 4-Nitroquinoline-1-Oxide-Induced Oral
      Carcinogenesis With an Alteration of Fatty Acid Metabolism.
AB  - Microbiota has been widely considered to play a critical role in human
      carcinogenesis. Human papilloma virus, hepatitis B and C virus, and Helicobacter
      pylori are implicated in the pathogenesis of cancer of uterine cervix, liver, and
      stomach, respectively. However, whether Porphyromonas gingivalis (P. gingivalis),
      a common Gram negative oral bacteria, is associated with oral carcinogenesis
      still remains unclear and its underlying mechanism needs to be addressed. Here,
      we established a combined experimental system of 4NQO-induced oral carcinoma
      model and chronic periodontitis model and investigated the effects of P.
      gingivalis infection on oral carcinogenesis and fatty acid metabolism during oral
      carcinogenesis. The data showed that in this animal model, P. gingivalis
      infection induced mice periodontitis, increased the tongue lesion size and
      multiplicity of each mouse and promoted oral cancer development. P. gingivalis
      treatment significantly increased the level of free fatty acids and altered the
      fatty acid profile in tongue tissues and the serum of mice. And P. gingivalis
      induced the formation of fatty liver of the mice. Besides, immunohistochemical
      analysis and qRT-PCR showed that the expression of fatty-acid synthase and acetyl
      CoA carboxylase 1 were increased in the tongue and liver tissues of 4NQO-treated
      mice infected with P. gingivalis. These results showed that P. gingivalis
      promoted oral carcinogenesis and aggravated disturbance of fatty acid metabolism,
      indicating a close association among P. gingivalis, lipid metabolic and oral
      carcinogenesis.

PMID- 30233550
TI  - Protein Composition of Mycobacterium smegmatis Differs Significantly Between
      Active Cells and Dormant Cells With Ovoid Morphology.
AB  - Mycobacteria are able to form dormant cells, which survive for a long time
      without multiplication. The molecular mechanisms behind prolonged survival of
      dormant cells are not fully described. In particular, little information is known
      on biochemical processes which might take place in cells under dormancy. To gain
      insight into this problem, Mycobacterium smegmatis cells in deep dormant state
      were obtained after gradual acidification of the growth medium in prolonged
      stationary phase followed by 1 month of storage at room temperature. Such cells
      were characterized by low metabolic activity, including respiration, resistance
      to antibiotics, and altered morphology. The protein composition of cytoplasm and
      membrane fractions obtained from active and dormant cells were compared by 2D
      electrophoresis. Almost half of the proteins found in the proteome of dormant
      cells were absent in that of active cells. This result differs significantly from
      published results obtained in other studies employing different models of
      mycobacterium dormancy. This discrepancy could be explained by a deeper dormancy
      developed in the present model. A feature of a "dormant proteome" is high
      representation of enzymes involved in glycolysis and defense systems that
      inactivate or detoxify reactive oxygen and nitrogen species, aldehydes, and
      oxidized lipids. Dormant mycobacteria are enriched by degradative enzymes, which
      could eliminate damaged molecules, or the products of such degradation could be
      reutilized by the cell during prolonged storage. We suggest that some enzymes in
      dormant cells are inactive, having been used upon transition to the dormant
      state, or proteins stored in dormant cells for further cell reactivation. At the
      same time, some proteins could be functional and play roles in maintenance of
      cell metabolism, albeit at a very slow rate. This study provides a clue as to
      which biochemical processes could be active under dormancy to ensure long-term
      viability of dormant mycobacteria.

PMID- 30233551
TI  - Circular and Leaderless Bacteriocins: Biosynthesis, Mode of Action, Applications,
      and Prospects.
AB  - Bacteriocins are a huge family of ribosomally synthesized peptides known to
      exhibit a range of bioactivities, most predominantly antibacterial activities.
      Bacteriocins from lactic acid bacteria are of particular interest due to the
      latter's association to food fermentation and the general notion of them to be
      safe. Among the family of bacteriocins, the groups known as circular bacteriocins
      and leaderless bacteriocins are gaining more attention due to their enormous
      potential for industrial application. Circular bacteriocins and leaderless
      bacteriocins, arguably the least understood groups of bacteriocins, possess
      distinctively peculiar characteristics in their structures and biosynthetic
      mechanisms. Circular bacteriocins have N-to-C- terminal covalent linkage forming
      a structurally distinct circular peptide backbone. The circular nature of their
      structures provides them superior stability against various stresses compared to
      most linear bacteriocins. The molecular mechanism of their biosynthesis, albeit
      has remained poorly understood, is believed to possesses huge application
      prospect as it can serve as scaffold in bioengineering other biologically
      important peptides. On the other hand, while most bacteriocins are synthesized as
      inactive precursor peptides, which possess an N-terminal leader peptide attached
      to a C-terminal propeptide, leaderless bacteriocins are atypical as they do not
      have an N-terminal leader peptide, hence the name. Leaderless bacteriocins are
      active right after translation as they do not undergo any post-translational
      processing common to other groups of bacteriocins. This "simplicity" in the
      biosynthesis of leaderless bacteriocins offers a huge commercial potential as
      scale-up production systems are considerably easier to assemble. In this review,
      we summarize the current studies of both circular and leaderless bacteriocins,
      highlighting the progress in understanding their biosynthesis, mode of action,
      application and their prospects.

PMID- 30233554
TI  - Comparative Evaluation of the LAMP Assay and PCR-Based Assays for the Rapid
      Detection of Alternaria solani.
AB  - Early blight (EB), caused by the pathogen Alternaria solani, is a major threat to
      global potato and tomato production. Early and accurate diagnosis of this disease
      is therefore important. In this study, we conducted a loop-mediated isothermal
      amplification (LAMP) assay, as well as conventional polymerase chain reaction
      (PCR), nested PCR, and quantitative real-time PCR (RT-qPCR) assays to determine
      which of these techniques was less time consuming, more sensitive, and more
      accurate. We based our assays on sequence-characterized amplified regions of the
      histidine kinase gene with an accession number (FJ424058). The LAMP assay
      provided more rapid and accurate results, amplifying the target pathogen in less
      than 60 min at 63 degrees C, with 10-fold greater sensitivity than conventional
      PCR. Nested PCR was 100-fold more sensitive than the LAMP assay and 1000-fold
      more sensitive than conventional PCR. qPCR was the most sensitive among the
      assays evaluated, being 10-fold more sensitive than nested PCR for the least
      detectable genomic DNA concentration (100 fg). The LAMP assay was more sensitive
      than conventional PCR, but less sensitive than nested PCR and qPCR; however, it
      was simpler and faster than the other assays evaluated. Despite of the
      sensitivity, LAMP assay provided higher specificity than qPCR. The LAMP assay
      amplified A. solani artificially, allowing us to detect naturally infect young
      potato leaves, which produced early symptoms of EB. The LAMP assay also achieved
      positive amplification using diluted pure A. solani culture instead of genomic
      DNA. Hence, this technique has greater potential for developing quick and
      sensitive visual detection methods than do other conventional PCR strategies for
      detecting A. solani in infected plants and culture, permitting early prediction
      of disease and reducing the risk of epidemics.

PMID- 30233552
TI  - Regulation of Apoptosis During Porcine Circovirus Type 2 Infection.
AB  - Apoptosis, an indispensable innate immune mechanism, regulates cellular
      homeostasis by removing unnecessary or damaged cells. It contains three signaling
      pathways: the mitochondria-mediated pathway, the death receptor pathway and the
      endoplasmic reticulum pathway. The importance of apoptosis in host defenses is
      stressed by the observation that multiple viruses have evolved various strategies
      to inhibit apoptosis, thereby blunting the host immune responses and promoting
      viral propagation. Porcine Circovirus type 2 (PCV2) utilizes various strategies
      to induce or inhibit programmed cell death. In this article, we review the latest
      research progress of the apoptosis mechanisms during infection with PCV2,
      including several proteins of PCV2 regulate apoptosis via interacting with host
      proteins and multiple signaling pathways involved in PCV2-induced apoptosis,
      which provides scientific basis for the pathogenesis and prevention of PCV2.

PMID- 30233553
TI  - APOBEC3B Activity Is Prevalent in Urothelial Carcinoma Cells and Only Slightly
      Affected by LINE-1 Expression.
AB  - The most common mutational signature in urothelial carcinoma (UC), the most
      common type of urinary bladder cancer is assumed to be caused by the misdirected
      activity of APOBEC3 (A3) cytidine deaminases, especially A3A or A3B, which are
      known to normally restrict the propagation of exogenous viruses and endogenous
      retroelements such as LINE-1 (L1). The involvement of A3 proteins in urothelial
      carcinogenesis is unexpected because, to date, UC is thought to be caused by
      chemical carcinogens rather than viral activity. Therefore, we explored the
      relationship between A3 expression and L1 activity, which is generally
      upregulated in UC. We found that UC cell lines highly express A3B and in some
      cases A3G, but not A3A, and exhibit corresponding cytidine deamination activity
      in vitro. While we observed evidence suggesting that L1 expression has a weak
      positive effect on A3B and A3G expression and A3B promoter activity, neither
      efficient siRNA-mediated knockdown nor overexpression of functional L1 elements
      affected catalytic activity of A3 proteins consistently. However, L1 knockdown
      diminished proliferation of a UC cell line exhibiting robust endogenous L1
      expression, but had little impact on a cell line with low L1 expression levels.
      Our results indicate that UC cells express A3B at levels exceeding A3A levels by
      far, making A3B the prime candidate for causing genomic mutations. Our data
      provide evidence that L1 activation constitutes only a minor and negligible
      factor involved in induction or upregulation of endogenous A3 expression in UC.

PMID- 30233555
TI  - Dietary Corn Bran Altered the Diversity of Microbial Communities and Cytokine
      Production in Weaned Pigs.
AB  - Corn bran (CB) has been used as an ingredient for pigs, but the underlying
      mechanisms that improve gut health is less clear. This study was conducted to
      investigate effects of dietary CB on growth performance, nutrient digestibility,
      plasma indices related to gut hormones and immunity, gut microbiota composition,
      and fermentation products in weaned pigs. A total of 60 weaned pigs were
      allocated to two dietary treatments, and piglets in each group received control
      (CON) diet or 5% CB diet for 28 days. Growth performance, nutrient digestibility,
      indices of gut hormones and immunity in plasma were evaluated. Microbiota
      composition in feces was determined using 16S rRNA amplicon sequencing, and
      fermentation products were measured by high-performance ion chromatography. The
      results showed that dietary CB did not affect growth performance, nutrient
      digestibility, gut hormones, or fermentation products in the trial (P > 0.05).
      There was an increased response to CB inclusion on interleukin-10 production (P <
      0.05). On day 28, piglets fed dietary CB had a higher shannon index (P < 0.05).
      The population of the Firmicutes in CB treatment were decreased (P < 0.05), while
      the percentage of the Bacteroidetes were increased (P < 0.05). In particular, the
      populations of Eubacterium corprostanoligenes, Pevotella, and Fibrobacter related
      to polysaccharide fermentation of cereal bran were increased (P < 0.05). In
      conclusion, a post-weaning diet containing 5% CB increased intestinal microbial
      diversity, especially higher richness of fibrolytic bacteria, and promoted anti
      inflammatory response to some extent in piglets, these changes should facilitate
      the adaptation of the digestive system of piglets in the subsequent growing
      phases.

PMID- 30233556
TI  - Prevalence and Characteristics of Campylobacter Throughout the Slaughter Process
      of Different Broiler Batches.
AB  - Handling and consumption of chicken meat are risk factors for human
      campylobacteriosis. This study was performed to describe the Campylobacter
      population in broiler carcasses and environmental samples throughout the
      slaughter process. Moreover, the genetic diversity and antimicrobial resistance
      of the Campylobacter strains were evaluated. Cloacal swabs, samples from
      carcasses at different stages, and environmental samples were collected thrice
      from the different flocks at the same abattoir located in Central Jiangsu, China.
      Campylobacter isolated from the three batches (n = 348) were identified as
      Campylobacter jejuni (n = 117) and Campylobacter coli (n = 151) by multiplex PCR.
      Characterization by multilocus sequence typing revealed a specific genotype of
      Campylobacter for each batch. Antimicrobial sensitivity to 18 antibiotics were
      analyzed for all selected strains according to the agar diffusion method
      recommended by the Clinical and Laboratory Standards Institute. Antibiotic
      susceptibility tests indicated that the majority of the tested isolates were
      resistant to quinolones (>89.7%). Less resistance to macrolide (59.8%),
      gentamicin (42.7%), amikacin (36.8%) was observed. Results showed that 94.0% of
      the tested strains demonstrated multidrug resistance.

PMID- 30233557
TI  - Application of MootralTM Reduces Methane Production by Altering the Archaea
      Community in the Rumen Simulation Technique.
AB  - The reduction of methane emissions by ruminants is a highly desirable goal to
      mitigate greenhouse gas emissions. Various feed additives have already been
      tested for their ability to decrease methane production; however, practical use
      is often limited due to negative effects on rumen fermentation or high costs.
      Organosulphur compounds from garlic (Allium sativum) and flavonoids have been
      identified as promising plant-derived compounds which are able to reduce methane
      production. Here, we evaluated the effects of a combination of garlic powder and
      bitter orange (Citrus aurantium) extracts, Mootral, on ruminal methane
      production, ruminal fermentation and the community of methanogenic Archaea by
      using the rumen simulation technique as ex vivo model. The experiment consisted
      of an equilibration period of 7 days, an experimental period of 8 days and a
      withdrawal period of 4 days. During the experimental period three fermenters each
      were either treated as controls (CON), received a low dose of Mootral (LD), a
      high dose of Mootral (HD), or monensin (MON) as positive control. Application of
      Mootral strongly reduced the proportion of methane in the fermentation gas and
      the production rate of methane. Moreover, the experimental mixture induced a dose
      dependent increase in the production rate of short chain fatty acids and in the
      molar proportion of butyrate. Some effects persisted during the withdrawal
      period. Both, single strand conformation polymorphism and Illumina MiSeq 16S rRNA
      amplicon sequencing indicated an archaeal community distinct from CON and MON
      samples in the LD and HD samples. Among archaeal families the percentage of
      Methanobacteriaceae was reduced during application of both doses of Mootral.
      Moreover, several significant differences were observed on OTU level among
      treatment groups and after withdrawal of the additives for LD and HD group. At
      day 14, 4 OTUs were positively correlated with methane production. In conclusion
      this mixture of garlic and citrus compounds appears to effectively reduce methane
      production by alteration of the archaeal community without exhibiting negative
      side effects on rumen fermentation.

PMID- 30233558
TI  - Enhanced Bacterial Growth and Gene Expression of D-Amino Acid Dehydrogenase With
      D-Glutamate as the Sole Carbon Source.
AB  - In a search for life-supporting, not life-assisting, D-amino acid metabolism, an
      environmental strain that grows better with D-glutamate as the sole carbon source
      was isolated from an ordinary river. The strain, designated as A25, exhibited a
      faster growth rate and greater cell yield with D-glutamate than with L-glutamate.
      Conversely, the D/L ratio of total cellular glutamate was as low as 4/96, which
      suggests that D-glutamate is more likely catabolized than anabolized. Strain A25
      was phylogenetically most closely related to the gamma-proteobacterial species
      Raoultella ornithinolytica, with a 16S rRNA gene sequence similarity of 100%. A
      standard strain, R. ornithinolytica JCM 6096T, also showed similarly enhanced
      growth with D-glutamate, which was proven for the first time. Gene expression of
      the enzymes involved in D-amino acid metabolism was assayed by reverse
      transcription quantitative PCR (RT-qPCR) using specifically designed primers. The
      targets were the genes encoding D-amino acid dehydrogenase (DAD; EC 1.4.99.1),
      glutamate racemase (EC 5.1.1.3), D-glutamate oxidase (EC 1.4.3.7 or EC 1.4.3.15),
      and UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-D-glutamate ligase (EC 6.3.2.9). As a
      result, the growth of strains A25 and R. ornithinolytica JCM 6096T on D-glutamate
      was conspicuously associated with the enhanced expression of the DAD gene (dadA)
      in the exponential phase compared with the other enzyme genes. Pseudomonas
      aeruginosa is also known to grow on D-glutamate as the sole carbon source but to
      a lesser degree than with L-glutamate. A standard strain of P. aeruginosa, JCM
      5962T, was tested for gene expression of the relevant enzymes by RT-qPCR and also
      showed enhanced dadA expression, but in the stationary phase. Reduction of
      ferricyanide with D-glutamate was detected in cell extracts of the tested
      strains, implying probable involvement of DAD in the D-glutamate catabolizing
      activity. DAD-mediated catalysis may have advantages in the one-step production
      of alpha-keto acids and non-production of H2O2 over other enzymes such as
      racemase and D-amino acid oxidase. The physiological and biochemical importance
      of DAD in D-amino acid metabolism is discussed.

PMID- 30233560
TI  - In vitro Prebiotic Effects of Bamboo Shoots and Potato Peel Extracts on the
      Proliferation of Lactic Acid Bacteria Under Simulated GIT Conditions.
AB  - The present study explored the possible prebiotic application of potato peel and
      bamboo shoot extracts for the proliferation of lactic acid bacteria (LAB) from
      diverse niches and their tolerance ability to simulated gastrointestinal tract
      (GIT) conditions was also examined. Initially, the complete 16S rDNA sequencing
      of selected isolates revealed them as Lactobacillus paracasei (6), Staphylococcus
      simulans (2), and Streptococcus thermophilus (1). Higher cell densities and rapid
      pH change were obtained from cultured media supplemented with BS (2%) and PP (2%)
      as a carbon source. Their higher tolerance and the lowest reducing sugar
      abilities were obtained for BS at pH 2.5 and 9.0, while at pH 3.5 and 8.0 for PP.
      The isolates were screened for additional functional and technological properties
      to harvest the most appropriate starter. The selected isolates harbored promising
      functional properties such as amylase presence, cell surface hydrophobicity,
      autoaggregation, proteolytic and lipolytic activity, antifungal action, as well
      as exopolysaccharide production. On the basis of these attributes,
      microencapsulated strain K3 was found resistant to gastrointestinal conditions
      after 2 h, resulting in significantly (p <= 0.05) improved survival compared to
      non-capsulated strain. The current approach presents an interesting economical
      strategy to modulate LAB through supplementation of plant-derived carbon sources
      as well as to enhance their survival under GIT.

PMID- 30233559
TI  - The Fluorescent D-Amino Acid NADA as a Tool to Study the Conditional Activity of
      Transpeptidases in Escherichia coli.
AB  - The enzymes responsible for the synthesis of the peptidoglycan (PG) layer
      constitute a fundamental target for a large group of antibiotics. The family of
      beta-lactam antibiotics inhibits the DD-transpeptidase (TPase) activity of the
      penicillin binding proteins (PBPs), whereas its subgroup of carbapenems can also
      block the TPase activity of the LD-TPases. D-Ala fluorescent probes, such as
      NADA, are incorporated into the PG presumably by TPases in Escherichia coli and
      can be used to study conditions that are required for their function. Of all LD
      TPases of E. coli, only LdtD was able to incorporate NADA during exponential
      growth. Overproduction of LdtD caused NADA to be especially inserted at mid cell
      in the presence of LpoB-activated PBP1b and the class C PBP5. Using the NADA
      assay, we could confirm that LpoB activates PBP1b at mid cell and that CpoB
      regulates the activity of PBP1b in vivo. Overproduction of LdtD was able to
      partly compensate for the inhibition of the cell division specific class B PBP3
      by aztreonam. We showed that class A PBP1c and the class C PBP6b cooperated with
      LdtD for NADA incorporation when PBP1b and PBP5 were absent, respectively.
      Besides, we proved that LdtD is active at pH 7.0 whereas LdtE and LdtF are more
      active in cells growing at pH 5.0 and they seem to cooperate synergistically. The
      NADA assay proved to be a useful tool for the analysis of the in vivo activities
      of the proteins involved in PG synthesis and our results provide additional
      evidence that the LD-TPases are involved in PG maintenance at different
      conditions.

PMID- 30233561
TI  - Establishment of an Efficient and Flexible Genetic Manipulation Platform Based on
      a Fosmid Library for Rapid Generation of Recombinant Pseudorabies Virus.
AB  - Conventional genetic engineering of pseudorabies virus (PRV) is essentially based
      on homologous recombination or bacterial artificial chromosome. However, these
      techniques require multiple plaque purification, which is labor-intensive and
      time-consuming. The aim of the present study was to develop an efficient, direct,
      and flexible genetic manipulation platform for PRV. To this end, the PRV genomic
      DNA was extracted from purified PRV virions and sheared into approximately 30-45
      kb DNA fragments. After end-blunting and phosphorylation, the DNA fragments were
      separated by pulsed-field gel electrophoresis, the recovered DNA fragments were
      inserted into the cloning-ready fosmids. The fosmids were then transformed into
      Escherichia coli and selected clones were end-sequenced for full-length genome
      assembly. Overlapping fosmid combinations that cover the complete genome of PRV
      were directly transfected into Vero cells and PRV was rescued. The morphology and
      one-step growth curve of the rescued virus were indistinguishable from those of
      the parent virus. Based on this system, a recombinant PRV expressing enhanced
      green fluorescent protein fused with the VP26 gene was generated within 2 weeks,
      and this recombinant virus can be used to observe the capsid transport in axons.
      The new genetic manipulation platform developed in the present study is an
      efficient, flexible, and stable method for the study of the PRV life cycle and
      development of novel vaccines.

PMID- 30233562
TI  - Anaerobic Ammonium Oxidation in Acidic Red Soils.
AB  - Anaerobic ammonium oxidation (anammox) has been proven to be an important
      nitrogen removal process in terrestrial ecosystems, particularly paddy soils.
      However, the contribution of anammox in acidic red soils to nitrogen loss has not
      been well-documented to date. Here, we investigated the activity, abundance, and
      distribution of anammox bacteria in red soils collected from nine provinces of
      Southern China. High-throughput sequencing analysis showed that Candidatus
      Brocadia dominates the anammox bacterial community (93.03% of sequence reads).
      Quantification of the hydrazine synthase gene (hzsB) and anammox 16S rRNA gene
      indicated that the abundance of anammox bacteria ranged from 6.20 * 106 to 1.81 *
      109 and 4.81 * 106 to 4.54 * 108 copies per gram of dry weight, respectively.
      Contributions to nitrogen removal by anammox were measured by a 15N isotope
      pairing assay. Anammox rates in red soil ranged from 0.01 to 0.59 nmol N g-1 h-1,
      contributing 16.67-53.27% to N2 production in the studied area, and the total
      amount of removed nitrogen by anammox was estimated at 2.33 Tg N per year in the
      natural red soils of southern China. Pearson correlation analyses revealed that
      the distribution of anammox bacteria significantly correlated with the
      concentration of nitrate and pH, whereas the abundance and activity of anammox
      bacteria were significantly influenced by the nitrate and total nitrogen
      concentrations. Our findings demonstrate that Candidatus Brocadia dominates
      anammox bacterial communities in acidic red soils and plays an important role in
      nitrogen loss of the red soil in Southern China.

PMID- 30233563
TI  - Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Gene Editing
      Technique in Xenotransplantation.
AB  - Genetically modified pigs have been considered favorable resources in
      xenotransplantation. Microinjection of randomly integrating transgenes into
      zygotes, somatic cell nuclear transfer, homologous recombination, zinc finger
      nucleases, transcription activator-like effector nucleases, and most recently,
      clustered regularly interspaced short palindromic repeats-cas9 (CRISPR/Cas9) are
      the techniques that have been used to generate these animals. Here, we provide an
      overview of the CRISPR approaches that have been used to modify genes which are
      vital in improving xenograft survival rate, including cytidine monophosphate-N
      acetylneuraminic acid hydroxylase, B1,4N-acetylgalactosaminyltransferase,
      isoglobotrihexosylceramide synthase, class I MHC, von Willebrand factor, C3, and
      porcine endogenous retroviruses. In addition, we will mention the importance of
      potential candidate genes which could be targeted using CRISPR/Cas9.

PMID- 30233565
TI  - Enhancement of Antitumor Vaccination by Targeting Dendritic Cell-Related IL-10.
AB  - Understanding mechanisms associated to dendritic cell (DC) functions has allowed
      developing new antitumor therapeutic vaccination strategies. However, these
      vaccines have demonstrated limited clinical results. Although the low
      immunogenicity of tumor antigens used and the presence of tumor-associated
      suppressive factors may in part account for these results, intrinsic vaccine
      related factors may also be involved. Vaccines modulate DC functions by inducing
      activating and inhibitory signals that determine ensuing T cell responses. In
      this mini review, we focus on IL-10, inhibitory cytokine induced in DC upon
      vaccination, which defines a suppressive cell subset, discussing its implications
      as a potential target in combined vaccination immunotherapies.

PMID- 30233567
TI  - A Small GTPase, RhoA, Inhibits Bacterial Infection Through Integrin Mediated
      Phagocytosis in Invertebrates.
AB  - The Ras GTPase superfamily, including more than 100 members, plays a vital role
      in a number of cellular processes, such as cytoskeleton recombination, gene
      expression, and signaling pathway regulation. Some members of the superfamily
      participate in innate immunity in animals. However, there have been few studies
      of RhoA on this aspect. In the present study, we identified a RhoA GTPase in the
      shrimp Marsupenaeus japonicus and named it MjRhoA. Expression of MjRhoA was
      significantly upregulated in hemocytes and heart of shrimp challenged with Vibrio
      anguillarum. Overexpression of MjRhoA in shrimp caused the total bacterial number
      to decrease significantly and knockdown of MjRhoA increased the bacterial number
      obviously, with a consequent decline in shrimp survival. These results confirmed
      the antibacterial function of MjRhoA in shrimp. Further study showed that rate of
      phagocytosis of hemocytes was decreased in MjRhoA-knockdown shrimp.
      Interestingly, we observed that MjRhoA was translocated onto the hemocyte
      membrane at 1 h post V. anguillarum challenge. The expression levels of the beta
      integrin-mediated phagocytosis markers ROCK2 and Arp2/3 declined significantly
      after knockdown of MjRhoA. These results suggested that the antibacterial
      function of MjRhoA was related to beta-integrin-mediated phagocytosis in shrimp.
      Our previous study identified that a C-type lectin, hFcLec4, initiated beta
      integrin mediated phagocytosis after bacterial infection. Thus, knockdown of
      hFcLec4 and beta-integrin was performed. The results showed that the
      translocation of MjRhoA from the cytoplasm to membrane was inhibited and the
      expression level of MjRhoA was decreased, suggesting that MjRhoA participated in
      hFcLec4-integrin mediated phagocytosis. Therefore, our study identified a new
      hFcLec4-integrin-RhoA dependent phagocytosis against bacterial infection in
      shrimp.

PMID- 30233564
TI  - Not All Immune Checkpoints Are Created Equal.
AB  - Antibodies that block T cell inhibition via the immune checkpoints CTLA-4 and PD
      1 have revolutionized cancer therapy during the last 15 years. T cells express
      additional inhibitory surface receptors that are considered to have potential as
      targets in cancer immunotherapy. Antibodies against LAG-3 and TIM-3 are currently
      clinically tested to evaluate their effectiveness in patients suffering from
      advanced solid tumors or hematologic malignancies. In addition, blockade of the
      inhibitory BTLA receptors on human T cells may have potential to unleash T cells
      to effectively combat cancer cells. Much research on these immune checkpoints has
      focused on mouse models. The analysis of animals that lack individual inhibitory
      receptors has shed some light on the role of these molecules in regulating T
      cells, but also immune responses in general. There are current intensive efforts
      to gauge the efficacy of antibodies targeting these molecules called immune
      checkpoint inhibitors alone or in different combinations in preclinical models of
      cancer. Differences between mouse and human immunology warrant studies on human
      immune cells to appreciate the potential of individual pathways in enhancing T
      cell responses. Results from clinical studies are not only highlighting the great
      benefit of immune checkpoint inhibitors for treating cancer but also yield
      precious information on their role in regulating T cells and other cells of the
      immune system. However, despite the clinical relevance of CTLA-4 and PD-1 and the
      high potential of the emerging immune checkpoints, there are still substantial
      gaps in our understanding of the biology of these molecules, which might prevent
      the full realization of their therapeutic potential. This review addresses PD-1,
      CTLA-4, BTLA, LAG-3, and TIM-3, which are considered major inhibitory immune
      checkpoints expressed on T cells. It provides summaries of our current conception
      of the role of these molecules in regulating T cell responses, and discussions
      about major ambiguities and gaps in our knowledge. We emphasize that each of
      these molecules harbors unique properties that set it apart from the others.
      Their distinct functional profiles should be taken into account in therapeutic
      strategies that aim to exploit these pathways to enhance immune responses to
      combat cancer.

PMID- 30233566
TI  - Precision Immunotherapy for Sepsis.
AB  - Decades of sepsis research into a specific immune system-targeting adjunctive
      therapy have not resulted in the discovery of an effective compound. Apart from
      antibiotics, source control, resuscitation and organ support, not a single
      adjunctive treatment is used in current clinical practice. The inability to
      determine the prevailing immunological phenotype of patients and the related
      large heterogeneity of study populations are regarded by many as the most
      important factors behind the disappointing results of past clinical trials. While
      the therapeutic focus has long been on immunosuppressive strategies, increased
      appreciation of the importance of sepsis-induced immunoparalysis in causing
      morbidity and mortality in sepsis patients has resulted in a paradigm shift in
      the sepsis research field towards strategies aimed at enhancing the immune
      response. However, similar to immunosuppressive therapies, precision medicine is
      imperative for future trials with immunostimulatory compounds to succeed. As
      such, identifying those patients with a severely suppressed or hyperactive immune
      system who will most likely benefit from either immunostimulatory or
      immunosuppressive therapy, and accurate monitoring of both the immune and
      treatment response is crucial. This review provides an overview of the challenges
      lying ahead on the path towards precision immunotherapy for patients suffering
      from sepsis.

PMID- 30233568
TI  - Peroxynitrite Exposure of CXCL12 Impairs Monocyte, Lymphocyte and Endothelial
      Cell Chemotaxis, Lymphocyte Extravasation in vivo and Anti-HIV-1 Activity.
AB  - CXCL12 is a chemotactic cytokine that attracts many different cell types for
      homeostasis and during inflammation. Under stress conditions, macrophages and
      granulocytes produce factors such as peroxynitrite as a consequence of their
      oxidative response. After short incubations of CXCL12 with peroxynitrite, the
      gradual nitration of Tyr7, Tyr61, or both Tyr7 and Tyr61 was demonstrated with
      the use of mass spectrometry, whereas longer incubations caused CXCL12
      degradation. Native CXCL12 and the nitrated forms, [3-NT61]CXCL12 and [3
      NT7/61]CXCL12, were chemically synthesized to evaluate the effects of Tyr
      nitration on the biological activity of CXCL12. All CXCL12 forms had a similar
      binding affinity for heparin, the G protein-coupled chemokine receptor CXCR4 and
      the atypical chemokine receptor ACKR3. However, nitration significantly enhanced
      the affinity of CXCL12 for chondroitin sulfate. Internalization of CXCR4 and beta
      arrestin 2 recruitment to CXCR4 was significantly reduced for [3-NT7/61]CXCL12
      compared to CXCL12, whereas beta-arrestin 2 recruitment to ACKR3 was similar for
      all CXCL12 variants. [3-NT7/61]CXCL12 was weaker in calcium signaling assays and
      in in vitro chemotaxis assays with monocytes, lymphocytes and endothelial cells.
      Surprisingly, nitration of Tyr61, but not Tyr7, partially protected CXCL12
      against cleavage by the specific serine protease CD26. In vivo, the effects were
      more pronounced compared to native CXCL12. Nitration of any Tyr residue
      drastically lowered lymphocyte extravasation to joints compared to native CXCL12.
      Finally, the anti-HIV-1 activity of [3-NT7]CXCL12 and [3-NT7/61]CXCL12 was
      reduced, whereas CXCL12 and [3-NT61]CXCL12 were equally potent. In conclusion,
      nitration of CXCL12 occurs readily upon contact with peroxynitrite and
      specifically nitration of Tyr7 fully reduces its in vitro and in vivo biological
      activities.

PMID- 30233569
TI  - Immunoadsorption of Desmoglein-3-Specific IgG Abolishes the Blister-Inducing
      Capacity of Pemphigus Vulgaris IgG in Neonatal Mice.
AB  - Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune blistering
      disease which is associated with autoantibodies directed against two desmosomal
      proteins, desmoglein (Dsg) 3 and 1. Treatment of PV is rather challenging and
      relies on the long-term use of systemic corticosteroids and additional
      immunosuppressants. More recently, autoantibody-depleting therapies such as
      rituximab, high-dose intravenous immunoglobulins, and immunoadsorption were shown
      to be valuable treatment options in PV. Specific removal of pathogenic
      autoantibodies would further increase efficacy and usability of immunoadsorption.
      Here, we tested the capacity of our recently developed prototypic Dsg1- and Dsg3
      specific adsorbers to remove circulating pathogenic autoantibodies from three
      different PV patients. The pathogenic potential of the Dsg3/1-depleted IgG
      fractions and the anti-Dsg3-specific IgG was explored in two different in vitro
      assays based on cultured human keratinocytes, the desmosome degradation assay and
      the dispase-based dissociation assay. In addition, the neonatal mouse model of PV
      was used. In both in vitro assays, no difference between the pathogenic effect of
      total PV IgG and anti-Dsg3-specific IgG was seen, while Dsg3/1-depleted and
      control IgG were not pathogenic. For the samples of all 3 PV patients, depletion
      of anti-Dsg3/1 IgG resulted in a complete loss of pathogenicity when injected
      into neonatal mice. In contrast, injection of anti-Dsg3-specific IgG, eluted from
      the column, induced gross blistering in the mice. Our data clearly show that anti
      Dsg3-specific IgG alone is pathogenic in vitro and in vivo, whereas Dsg3/1
      depletion results in a complete loss of pathogenicity. Furthermore, our data
      suggest that Dsg-specific adsorption may be a suitable therapeutic modality to
      efficiently reduce pathogenic autoantibodies in patients with severe PV.

PMID- 30233570
TI  - Early Resistance of Non-virulent Mycobacterial Infection in C57BL/6 Mice Is
      Associated With Rapid Up-Regulation of Antimicrobial Cathelicidin Camp.
AB  - Early clearance of tuberculosis is the successful eradication of inhaled bacteria
      before the development of an adaptive immune response. We previously showed, by
      utilizing a non-virulent mycobacteria infection model, that C57BL/6 mice are more
      efficient than BALB/c in their control of bacterial growth in the lungs during
      the first weeks of the infection. Here, we assessed early (within 1-3 days)
      innate immune events locally in the lungs to identify factors that may contribute
      to the control of non-virulent mycobacterial burden. We confirmed that C57BL/6
      mice are more resistant to infection compared with BALB/c after intranasal
      inoculation with mycobacterium. Transcriptomic analyses revealed a remarkably
      silent signature in C57BL/6 mice despite effective control of bacterial growth.
      In contrast, BALB/c mice up-regulated genes associated with neutrophil and
      myeloid cell chemotaxis and migration. Flow cytometry analyses corroborated the
      transcriptomic analyses and demonstrated influx of both neutrophil and myeloid
      cell populations in BALB/c mice, while these did not increase in C57BL/6 mice. We
      further detected increased release of TNF-alpha from BALB/c lung cells but
      limited release from C57BL/6-derived cells. However, C57BL/6 mice showed a marked
      early up-regulation of the Camp gene, encoding the cathelicidin CRAMP peptide,
      post-mycobacterial exposure. CRAMP (LL-37 in human) expression in the lungs was
      confirmed using immunofluorescence staining. Altogether, these findings show that
      C57BL/6 mice can clear the mycobacterial infection early and that this early
      control is associated with high CRAMP expression in the lungs without concomitant
      influx of immune cells. The role of CRAMP/LL-37 during mycobacterial infection
      may be relevant for novel protective strategies, and warrants further studies of
      human cohorts.

PMID- 30233571
TI  - An Approach to the Evaluation of Persistent Hypereosinophilia in Pediatric
      Patients.
AB  - Hypereosinophilia (HE) is currently defined by a peripheral blood absolute
      eosinophil count (AEC) of >=1,500 cells/microL. Although mild blood eosinophilia
      (AEC 500-1,500 cells/microL) is observed relatively frequently within the
      pediatric population, persistent HE is uncommon and should prompt additional
      clinical evaluation. While the clinical manifestations and underlying etiologies
      of HE in adults have been well-characterized, there is a paucity of data on HE in
      children. Limited evidence suggests that many similarities between adult and
      pediatric HE likely exist, but some important differences remain between these
      populations. The evaluation of HE in children can be challenging given the broad
      differential diagnosis, which includes primary hematologic disorders and
      secondary eosinophilia in which the increased eosinophil levels are propagated by
      disease states that promote eosinophil production and survival. On the basis of
      the underlying etiology, clinical manifestations can range from benign, self
      resolving elevations in the AEC to life-threatening disorders with the potential
      for significant end-organ damage. Given the broad differential diagnosis of HE,
      it remains essential to systematically approach the evaluation of unexplained HE
      in children. This review will discuss the differential diagnosis for pediatric
      HE, highlighting etiologies that are more prevalent within the pediatric
      population. Additionally, a summary of the epidemiology of pediatric HE will be
      presented, with focus on some of the differences that exist between pediatric and
      adult HE. Finally, a directed approach to the diagnostic evaluation of children
      with HE will be discussed.

PMID- 30233572
TI  - Antigen Uptake by Langerhans Cells Is Required for the Induction of Regulatory T
      Cells and the Acquisition of Tolerance During Epicutaneous Immunotherapy in OVA
      Sensitized Mice.
AB  - The skin is a major immunologic organ that may induce protection, sensitization
      or tolerance. Epicutaneous immunotherapy (EPIT) has been proposed as an
      attractive strategy to actively treat food allergy and has been shown to induce
      tolerance in sensitized mice through the induction of Foxp3+ regulatory T cells
      (Tregs), especially CD62L+ Tregs. Among immune cells in the skin, dendritic cells
      are key players in antigen-specific immune activation or regulation. The role of
      different populations of skin DCs in tolerance induction remains to be
      elucidated. Using OVA-sensitized BALB/c mice, we demonstrated that the
      application of a patch containing OVA-A647 to the skin resulted in allergen
      uptake by Langerhans cells (LCs) and CD11b+ dermal cDC2 and subsequent migration
      into skin draining lymph nodes. These 2 populations induced Foxp3 expression in
      CD4+ cells in vitro. Only LCs induced LAP+ cells and CD62L+ Tregs. Using Langerin
      eGFP-DTR mice, we analyzed the role of LCs in the mechanisms of tolerance
      induction by EPIT in vivo. Following complete depletion of LCs, a dramatic
      decrease in the number of OVA+ DCs and OVA+ CD11b+ dermal cDC2 was observed in
      skin draining lymph nodes 48 h after epicutaneous application. Likewise, 2 weeks
      of EPIT in non-depleted mice induced Foxp3+ Tregs, especially CD62L+, and LAP+
      Tregs in skin draining lymph nodes and spleen, whereas no induction of Tregs was
      observed in LC-depleted mice. Following 8 weeks of treatment, EPIT-treated mice
      showed significant protection against anaphylaxis accompanied by a significant
      increase of Foxp3+ Tregs, especially CD62L+ Tregs, which was not seen in the
      absence of LCs. In summary, although both LCs and CD11b+ dermal cDC2s could
      induce regulatory T cells, the absence of LCs during EPIT impaired treatment
      efficacy, indicating their crucial role in skin-induced tolerance.

PMID- 30233573
TI  - Polyanhydride Nanovaccine Induces Robust Pulmonary B and T Cell Immunity and
      Confers Protection Against Homologous and Heterologous Influenza A Virus
      Infections.
AB  - Influenza A virus (IAV) is a major cause of respiratory illness. Given the
      disease severity, associated economic costs, and recent appearance of novel IAV
      strains, there is a renewed interest in developing novel and efficacious
      "universal" IAV vaccination strategies. Recent studies have highlighted that
      immunizations capable of generating local (i.e., nasal mucosa and lung) tissue
      resident memory T and B cells in addition to systemic immunity offer the greatest
      protection against future IAV encounters. Current IAV vaccines are designed to
      largely stimulate IAV-specific antibodies, but do not generate the lung-resident
      memory T and B cells induced during IAV infections. Herein, we report on an
      intranasally administered biocompatible polyanhydride nanoparticle-based IAV
      vaccine (IAV-nanovax) capable of providing protection against subsequent
      homologous and heterologous IAV infections in both inbred and outbred
      populations. Our findings also demonstrate that vaccination with IAV-nanovax
      promotes the induction of germinal center B cells within the lungs, both systemic
      and lung local IAV-specific antibodies, and IAV-specific lung-resident memory CD4
      and CD8 T cells. Altogether our findings show that an intranasally administered
      nanovaccine can induce immunity within the lungs, similar to what occurs during
      IAV infections, and thus could prove useful as a strategy for providing
      "universal" protection against IAV.

PMID- 30233574
TI  - Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and
      Associated With the Clinical Phenotype.
AB  - Introduction: Zymogen granule glycoprotein 2 (GP2) was demonstrated as first
      autoimmune mucosal target in primary sclerosing cholangitis (PSC) associated with
      disease severity. Autoantibodies to four GP2 isoforms (aGP21-4) were found in
      patients with inflammatory bowel diseases but reactivity against specific GP2
      epitopes has not been investigated in PSC yet. Hence, the prevalence of aGP21-4
      and their association with the PSC phenotype for risk prediction were examined.
      Methods: GP2 isoforms were stably expressed as glycosylphosphatidyl - inositol
      anchored molecules in the membrane of HEp-2 cells and used as autoantigenic
      targets in indirect immunofluorescence assay (IFA). aGP21-4 IgA and IgG were
      detected by IFA in 212 PSC patients of four European university hospitals and 145
      controls comprising 95 patients with cystic fibrosis and 50 healthy subjects.
      Results: Combined aGP21 and aGP24 IgA testing with a sensitivity of 66.0% and a
      specificity of 97.9% resulted in the best diagnostic performance (Youden index:
      0.64) regarding all aGP2 and combinations thereof. aGP24 IgA positivity is
      significantly associated with the presence of cirrhosis in PSC (p = 0.0056).
      Logistic regression revealed the occurrence of aGP21 IgA (odds ratio [OR] 1.38,
      95% confidence interval [CI]: 1.03-1.86) and aGP24 IgA (OR 1.52, 95%CI: 1.07
      2.15) along with male gender (OR 0.51, 95%CI: 0.27-0.97) and older age (OR 1.03
      95%CI: 1.01-1.05) as significant risks for the concomitant presence of cirrhosis
      in PSC. Conclusions: Combined aGP21 and aGP24 IgA analysis is preferred to single
      aGP2 isoform analysis for sensitive PSC autoantibody testing. Positivity for
      aGP21 and aGP24 IgA is associated with cirrhosis in PSC and could be used for
      risk stratification.

PMID- 30233576
TI  - CD18 Regulates Monocyte Hematopoiesis and Promotes Resistance to Experimental
      Schistosomiasis.
AB  - Infection with Schistosoma mansoni causes a chronic parasitic disease that
      progress to severe liver and gastrointestinal damage, and eventually death.
      During its development into mammalian hosts, immature schistosomula transit
      through the lung vasculature before they reach the liver to mature into adult
      worms. A low grade inflammatory reaction is induced during this process. However,
      molecules that are required for efficient leukocyte accumulation in the lungs of
      S. mansoni-infected subjects are unknown. In addition, specific leukocyte subsets
      that mediate pulmonary response during S. mansoni migration through the lung
      remain to be elucidated. beta2 integrins are fundamental regulators of leukocyte
      trans-endothelial migration and function. Therefore, we investigated their role
      during experimental schistosomiasis. Mice that express low levels of CD18 (the
      common beta2 integrin subunit) and wild type C57BL/6 mice were subcutaneously
      infected with S. mansoni cercariae. Cellular profiles of lungs and livers were
      evaluated in different time points after infection by flow cytometry. Low levels
      of CD18 affected the accumulation of patrolling Ly6Clow, intermediate Ly6Cinter
      monocytes, monocyte-derived macrophages and monocyte-derived dendritic cells in
      the lungs 7 days after infection. This correlated with increased TNF-alpha
      levels. Strikingly, low CD18 expression resulted in monocytopenia both in the
      peripheral blood and bone marrow during acute infection. After 48 days, S.
      mansoni worm burdens were higher in the hepatic portal system of CD18low mice,
      which also displayed reduced hepatic accumulation of patrolling Ly6Clow and
      intermediate Ly6Cinter, but not inflammatory Ly6Chigh monocytes. Higher parasite
      burden resulted in increased granulomatous lesions in the liver, increased egg
      deposition and enhanced mortality. Overall, our data point for a fundamental role
      of CD18 for monocyte hematopoiesis during infection, which promotes an efficient
      host response against experimental schistosomiasis.

PMID- 30233575
TI  - Regulation, Communication, and Functional Roles of Adipose Tissue-Resident CD4+ T
      Cells in the Control of Metabolic Homeostasis.
AB  - Evidence accumulated over the past few years has documented a critical role for
      adipose tissue (AT)-resident immune cells in the regulation of local and systemic
      metabolic homeostasis. In the lean state, visceral adipose tissue (VAT) is
      predominated by anti-inflammatory T-helper 2 (Th2) and regulatory T (Treg) cell
      subsets. As obesity progresses, the population of Th2 and Treg cells decreases
      while that of the T-helper 1 (Th1) and T-helper 17 (Th17) cells increases,
      leading to augmented inflammation and insulin resistance. Notably, recent studies
      also suggest a potential role of CD4+ T cells in the control of thermogenesis and
      energy homeostasis. In this review, we have summarized recent advances in
      understanding the characteristics and functional roles of AT CD4+ T cell subsets
      during obesity and energy expenditure. We have also discussed new findings on the
      crosstalk between CD4+ T cells and local antigen-presenting cells (APCs)
      including adipocytes, macrophages, and dendritic cells (DCs) to regulate AT
      function and metabolic homeostasis. Finally, we have highlighted the therapeutic
      potential of targeting CD4+ T cells as an effective strategy for the treatment of
      obesity and its associated metabolic diseases.

PMID- 30233577
TI  - Selection of Tumor-Specific Cytotoxic T Lymphocytes in Acute Myeloid Leukemia
      Patients Through the Identification of T-Cells Capable to Establish Stable
      Interactions With the Leukemic Cells: "Doublet Technology".
AB  - The relevance of the immune system in cancer has long been studied. Autologous
      adoptive T cell therapies, based on the use of tumor infiltrating lymphocytes
      (TILs), have made great progress in recent years for the treatment of solid
      tumors, especially melanoma. However, further work is needed to isolate tumor
      reactive T cells among patients diagnosed with hematologic malignancies. The
      dynamics of the interaction between T cells and antigen presenting cells (APC)
      dictate the quality of the immune responses. While stable joints between target
      cells and T lymphocytes lead to the induction of T cell activation and immune
      response, brief contacts contribute to the induction of immune-tolerance. Taking
      advantage of the strong interaction between target cell and activated T-cells, we
      show the feasibility to identify and isolate tumor-specific cytotoxic T
      lymphocytes (CTLs) from acute myeloid leukemia (AML) patients by flow cytometry.
      Using this technology, CTLs bound through T cell receptor (TCR) to tumor cells
      can be identified in peripheral blood and bone marrow and subsequently selected
      and isolated by FACS-based cell sorting. These CTLs display higher percentage of
      effector cells and marked cytotoxic activity against AML blasts. In conclusion,
      we have developed a new procedure to identify and select specific cytotoxic T
      cells in patients diagnosed with acute myeloid leukemia.

PMID- 30233578
TI  - Inhibition of Glycolysis Reduces Disease Severity in an Autoimmune Model of
      Rheumatoid Arthritis.
AB  - The K/BxN mouse is a spontaneous model of arthritis driven by T cell receptor
      transgenic CD4+ T cells from the KRN strain that are activated by glucose-6
      phosphate isomerase (GPI) peptides presented by the H-2g7 allele from the NOD
      strain. It is a model of autoimmune seropositive arthritis because the production
      of anti-GPI IgG is necessary and sufficient for joint pathology. The production
      of high levels of anti-GPI IgG requires on the expansion of CD4+ follicular
      helper T (Tfh) cells. The metabolic requirements of this expansion have never
      been characterized. Based on the therapeutic effects of the combination of
      metformin and 2-deoxyglucose (2DG) in lupus models that normalized the expansion
      of effector CD4+ T cells. We showed that the CD4+ T cells and to a lesser extent,
      the B cells from K/BxN mice are more metabolically active than the KRN controls.
      Accordingly, preventive inhibition of glycolysis with 2DG significantly reduced
      joint inflammation and the activation of both adaptive and innate immune cells,
      as well as the production of pathogenic autoantibodies. However, contrary to the
      lupus-prone mice, the addition of metformin had little beneficial effect,
      suggesting that glycolysis is the major driver of immune activation in this
      model. We propose that K/BxN mice are another model in which autoreactive Tfh
      cells are highly glycolytic and that their function can be limited by inhibiting
      glucose metabolism.

PMID- 30233580
TI  - Increased Binding of Specificity Protein 1 to the IL21R Promoter in B Cells
      Results in Enhanced B Cell Responses in Rheumatoid Arthritis.
AB  - B cells are implicated in rheumatoid arthritis (RA) based on the presence of
      autoantibodies and the therapeutic response to B cell depletion. IL-21 has a
      significant role in B cell development and function. Here we assess B cell
      responses to IL-21 and the mechanisms responsible for altered IL-21R expression
      in RA. Flow cytometry of PBMC and cultured B cells was used to quantify protein
      and mRNA levels of IL-21R, IL-21 signaling through pSTAT3, specificity protein 1
      (SP1) and to determine cytokine production (IL-6) and maturation status of B
      cells in RA and healthy control subjects. SP1 binding to the IL21R promoter
      region in B cells was assessed with ChIP-qPCR. We demonstrate an increase in IL
      21R expression in total and memory B cells from RA subjects, which correlated
      with responsiveness to IL-21 stimulation. Stimulation of naive RA B cells with IL
      21 and CD40L resulted in an increase in differentiation into plasmablasts and an
      increase in IL-6 production in comparison to healthy controls, which was dose
      dependent on IL-21 stimulation. IL-21R expression on memory B cells in RA
      synovial fluid was comparable to peripheral blood making our study pertinent to
      understanding B cell responses in the joint and site of inflammation. We
      identified an increase in SP1 protein and mRNA in RA B cells and demonstrate an
      increase in binding of SP1 to the IL21R promoter region, which suggests a
      mechanism by which IL-21R expression is enhanced on B cells in RA. Taken
      together, our results indicate a mechanism by which IL-21 enhances B cell
      development and function in RA through an SP1 mediated increase in IL-21R
      expression on B cells.

PMID- 30233581
TI  - Inefficient N2-Like Neutrophils Are Promoted by Androgens During Infection.
AB  - Neutrophils are major effectors of acute inflammation against infection and
      tissue damage, with ability to adapt their phenotype according to the
      microenvironment. Although sex hormones regulate adaptive immune cells, which
      explains sex differences in immunity and infection, little information is
      available about the effects of androgens on neutrophils. We therefore aimed to
      examine neutrophil recruitment and plasticity in androgen-dependent and 
      independent sites under androgen manipulation. By using a bacterial model of
      prostate inflammation, we showed that neutrophil recruitment was higher in
      testosterone-treated rats, with neutrophil accumulation being positively
      correlated to serum levels of testosterone and associated to stronger
      inflammatory signs and tissue damage. Testosterone also promoted LPS-induced
      neutrophil recruitment to the prostate, peritoneum, and liver sinusoids, as
      revealed by histopathology, flow cytometry, and intravital microscopy.
      Strikingly, neutrophils in presence of testosterone exhibited an impaired
      bactericidal ability and a reduced myeloperoxidase activity. This inefficient
      cellular profile was accompanied by high expression of the anti-inflammatory
      cytokines IL10 and TGFbeta1, which is compatible with the "N2-like" neutrophil
      phenotype previously reported in the tumor microenvironment. These data reveal an
      intriguing role for testosterone promoting inefficient, anti-inflammatory
      neutrophils that prolong bacterial inflammation, generating a pathogenic
      environment for several conditions. However, these immunomodulatory properties
      might be beneficially exploited in autoimmune and other non-bacterial diseases.

PMID- 30233582
TI  - Lipidomimetic Compounds Act as HIV-1 Entry Inhibitors by Altering Viral Membrane
      Structure.
AB  - The envelope of Human Immunodeficiency Virus type 1 (HIV-1) consists of a liquid
      ordered membrane enriched in raft lipids and containing the viral glycoproteins.
      Previous studies demonstrated that changes in viral membrane lipid composition
      affecting membrane structure or curvature can impair infectivity. Here, we
      describe novel antiviral compounds that were identified by screening compound
      libraries based on raft lipid-like scaffolds. Three distinct molecular structures
      were chosen for mode-of-action studies, a sterol derivative (J391B), a
      sphingosine derivative (J582C) and a long aliphatic chain derivative (IBS70). All
      three target the viral membrane and inhibit virus infectivity at the stage of
      fusion without perturbing virus stability or affecting virion-associated envelope
      glycoproteins. Their effect did not depend on the expressed envelope
      glycoproteins or a specific entry route, being equally strong in HIV pseudotypes
      carrying VSV-G or MLV-Env glycoproteins. Labeling with laurdan, a reporter of
      membrane order, revealed different membrane structure alterations upon compound
      treatment of HIV-1, which correlated with loss of infectivity. J582C and IBS70
      decreased membrane order in distinctive ways, whereas J391B increased membrane
      order. The compounds' effects on membrane order were reproduced in liposomes
      generated from extracted HIV lipids and thus independent both of virion proteins
      and of membrane leaflet asymmetry. Remarkably, increase of membrane order by
      J391B required phosphatidylserine, a lipid enriched in the HIV envelope.
      Counterintuitively, mixtures of two compounds with opposite effects on membrane
      order, J582C and J391B, did not neutralize each other but synergistically
      inhibited HIV infection. Thus, altering membrane order, which can occur by
      different mechanisms, constitutes a novel antiviral mode of action that may be of
      general relevance for enveloped viruses and difficult to overcome by resistance
      development.

PMID- 30233583
TI  - Cytotoxic Necrotizing Factor 1 Downregulates CD36 Transcription in Macrophages to
      Induce Inflammation During Acute Urinary Tract Infections.
AB  - Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC)
      induce cystitis, pyelonephritis, and can cause kidney scarring and failure if
      inflammation is not under control. The detailed effects of cytotoxic necrotizing
      factor 1 (CNF1), the key UPEC toxin, on the pathogenicity of UPEC remain unclear.
      CD36 is an important scavenger receptor, responsible for pathogen and apoptotic
      cell clearance, and plays an essential role in host immune defense and
      homeostasis. Regulation of CD36 by bacterial toxins has not been reported. In
      this study, using a pyelonephritis mouse model, CNF1 was observed to contribute
      to increasing neutrophils and bacterial titers in infected bladder and kidney
      tissues, resulting in severe inflammation and tissue damage. CD36 expression in
      macrophages was found to be decreased by CNF1 in vitro and in vivo. We
      demonstrated that CNF1 attenuated CD36 transcription by decreasing expressions of
      its upstream transcription factors LXRbeta and C/EBPalpha and their recruitment
      to the CD36 promotor. In addition, Cdc42 was found to be involved in CNF1
      mediated downregulation of LXRbeta. Our study investigated the pathogenesis of
      cnf1-carrying UPEC, which affected host innate immune defenses and homeostasis
      through regulation of CD36 in macrophages during acute UTIs.

PMID- 30233584
TI  - The Pulmonary Extracellular Matrix Is a Bactericidal Barrier Against Haemophilus
      influenzae in Chronic Obstructive Pulmonary Disease (COPD): Implications for an
      in vivo Innate Host Defense Function of Collagen VI.
AB  - Non-typeable Haemophilus influenzae (NTHi) is a Gram-negative human commensal
      commonly residing in the nasopharynx of preschool children. It occasionally
      causes upper respiratory tract infection such as acute otitis media, but can also
      spread to the lower respiratory tract causing bronchitis and pneumonia. There is
      increasing recognition that NTHi has an important role in chronic lower
      respiratory tract inflammation, particularly in persistent infection in patients
      suffering from chronic obstructive pulmonary disease (COPD). Here, we set out to
      assess the innate protective effects of collagen VI, a ubiquitous extracellular
      matrix component, against NTHi infection in vivo. In vitro, collagen VI rapidly
      kills bacteria through pore formation and membrane rupture, followed by exudation
      of intracellular content. This effect is mediated by specific binding of the von
      Willebrand A (VWA) domains of collagen VI to the NTHi surface adhesins protein E
      (PE) and Haemophilus autotransporter protein (Hap). Similar observations were
      made in vivo specimens from murine airways and COPD patient biopsies. NTHi
      bacteria adhered to collagen fibrils in the airway mucosa and were rapidly killed
      by membrane destabilization. The significance in host-pathogen interplay of one
      of these molecules, PE, was highlighted by the observation that it confers
      partial protection from bacterial killing. Bacteria lacking PE were more prone to
      antimicrobial activity than NTHi expressing PE. Altogether the data shed new
      light on the carefully orchestrated molecular events of the host-pathogen
      interplay in COPD and emphasize the importance of the extracellular matrix as a
      novel branch of innate host defense.

PMID- 30233585
TI  - Cellular Clearance and Biological Activity of Calciprotein Particles Depend on
      Their Maturation State and Crystallinity.
AB  - Background: The liver-derived plasma protein fetuin-A is a systemic inhibitor of
      ectopic calcification. Fetuin-A stabilizes saturated mineral solutions by forming
      colloidal protein-mineral complexes called calciprotein particles (CPP). CPP are
      initially spherical, amorphous and soft, and are referred to as primary CPP.
      These particles spontaneously convert into secondary CPP, which are larger,
      oblongate, more crystalline, and less soluble. CPP mediate excess mineral
      transport and clearance from circulation. Methods: We studied by intravital two
      photon microscopy the clearance of primary vs. secondary CPP by injecting i.v.
      synthetic fluorescent CPP in mice. We analyzed CPP organ distribution and
      identified CPP endocytosing cells by immunofluorescence. Cellular clearance was
      studied using bone marrow-derived mouse wildtype and scavenger receptor A (SRA)
      deficient macrophages, as well as human umbilical cord endothelial cells (HUVEC),
      monocyte-derived macrophages (hMDM), and human aortic endothelial cells (haEC).
      We employed mouse wildtype and mutant immortalized macrophages to analyze CPP
      induced inflammasome activation and cytokine secretion. Results: In live mice,
      only primary CPP were rapidly cleared by liver sinusoidal endothelial cells
      (LSEC), whereas primary and secondary CPP were cleared by Kupffer cells.
      Scavenger receptor A (SRA)-deficient bone marrow macrophages endocytosed
      secondary CPP less well than did wildtype macrophages. In contrast, primary CPP
      endocytosis did not depend on the presence of SRA, suggesting involvement of an
      alternative clearance pathway. CPP triggered TLR4 dependent TNFalpha and IL-1beta
      secretion in cultured macrophages. Calcium content-matched primary CPP caused
      twice more IL-1beta secretion than did secondary CPP, which was associated with
      increased calcium-dependent inflammasome activation, suggesting that
      intracellular CPP dissolution and calcium overload may cause this inflammation.
      Conclusions: Secondary CPP are endocytosed by macrophages in liver and spleen via
      SRA. In contrast, our results suggest that primary CPP are cleared by LSEC via an
      alternative pathway. CPP induced TLR4-dependent TNFalpha and inflammasome
      dependent IL-1beta secretion in macrophages suggesting that inflammation and
      calcification may be considered consequences of prolonged CPP presence and
      clearance.

PMID- 30233579
TI  - Turn Back the TIMe: Targeting Tumor Infiltrating Myeloid Cells to Revert Cancer
      Progression.
AB  - Tumor cells frequently produce soluble factors that favor myelopoiesis and
      recruitment of myeloid cells to the tumor microenvironment (TME). Consequently,
      the TME of many cancer types is characterized by high infiltration of monocytes,
      macrophages, dendritic cells and granulocytes. Experimental and clinical studies
      show that most myeloid cells are kept in an immature state in the TME. These
      studies further show that tumor-derived factors mold these myeloid cells into
      cells that support cancer initiation and progression, amongst others by enabling
      immune evasion, tumor cell survival, proliferation, migration and metastasis. The
      key role of myeloid cells in cancer is further evidenced by the fact that they
      negatively impact on virtually all types of cancer therapy. Therefore, tumor
      associated myeloid cells have been designated as the culprits in cancer. We
      review myeloid cells in the TME with a focus on the mechanisms they exploit to
      support cancer cells. In addition, we provide an overview of approaches that are
      under investigation to deplete myeloid cells or redirect their function, as these
      hold promise to overcome resistance to current cancer therapies.

PMID- 30233587
TI  - Mucosal-Associated Invariant T Cells Improve Nonalcoholic Fatty Liver Disease
      Through Regulating Macrophage Polarization.
AB  - Mucosal-associated invariant T (MAIT) cells, a novel population of innate-like
      lymphocytes, have been involved in various inflammatory and autoimmune diseases.
      However, their role in the development of nonalcoholic fatty liver disease
      (NAFLD) remains unclear. In this study, we investigated the alterations of
      phenotype and immunological function of MAIT cells in NAFLD. Analysis of PBMCs in
      60 patients with NAFLD and 48 healthy controls (HC) revealed that circulating
      MAIT cell frequency decreased in NAFLD, especially in the patients with higher
      serum levels of gamma-glutamyl transferase or total triglyceride. Functional
      alterations of circulating MAIT cells were also detected in NAFLD patients, such
      as the increased production of IL-4 whereas the decreased production of IFN-gamma
      and TNF-alpha. Furthermore, elevated expression of CXCR6 was observed in
      circulating MAIT cells of patients. Meanwhile, we found an increased number of
      MAIT cells in the livers of NAFLD, and the number was even greater in patients
      with higher NAFLD activity score. Moreover, activated MAIT cells induced
      monocytes/macrophages differentiation into M2 phenotype in vitro. Additionally,
      MAIT cells were enriched and displayed Th2 type cytokines profile in livers of
      wild type mice fed with methionine and choline deficient diet (MCD). Notably,
      mice deficient of MAIT cells exhibited more severe hepatic steatosis and
      inflammation upon MCD, accompanied with more CD11c+ proinflammatory macrophages
      (M1) and less CD206+ anti-inflammatory macrophages (M2) in livers. Our results
      indicate that MAIT cells protect against inflammation in NAFLD through producing
      regulatory cytokines and inducing anti-inflammatory macrophage polarization,
      which may provide novel therapeutic strategies for NAFLD.

PMID- 30233586
TI  - Emerging Developments in Microbiome and Microglia Research: Implications for
      Neurodevelopmental Disorders.
AB  - From immunology to neuroscience, interactions between the microbiome and host are
      increasingly appreciated as potent drivers of health and disease. Epidemiological
      studies previously identified compelling correlations between perinatal
      microbiome insults and neurobehavioral outcomes, the mechanistic details of which
      are just beginning to take shape thanks to germ-free and antibiotics-based animal
      models. This review summarizes parallel developments from clinical and
      preclinical research that suggest neuroactive roles for gut bacteria and their
      metabolites. We also examine the nascent field of microbiome-microglia crosstalk
      research, which includes pharmacological and genetic strategies to inform
      functional capabilities of microglia in response to microbial programming.
      Finally, we address an emerging hypothesis behind neurodevelopmental disorders,
      which implicates microbiome dysbiosis in the atypical programming of neuroimmune
      cells, namely microglia.

PMID- 30233588
TI  - PD-1 Expression on Mycobacterium tuberculosis-Specific CD4 T Cells Is Associated
      With Bacterial Load in Human Tuberculosis.
AB  - Persistent antigen stimulation in chronic infections has been associated with
      antigen-specific T cell dysfunction and upregulation of inhibitory receptors,
      including programmed cell death protein 1 (PD-1). Pulmonary tuberculosis (TB)
      disease is characterized by high levels of Mycobacterium tuberculosis (Mtb), yet
      the relationship between bacterial load, PD-1 expression, and Mtb-specific T cell
      function in human TB has not been well-defined. Using peripheral blood samples
      from adults with LTBI and with pulmonary TB disease, we tested the hypothesis
      that PD-1 expression is associated with bacterial load and functional capacity of
      Mtb-specific T cell responses. We found that PD-1 was expressed at significantly
      higher levels on Th1 cytokine-producing Mtb-specific CD4 T cells from patients
      with smear-positive TB, compared with smear-negative TB and LTBI, which decreased
      after completion of anti-TB treatment. By contrast, expression of PD-1 on Mtb
      specific CD8 T cells was significantly lower than on Mtb-specific CD4 T cells and
      did not differ by Mtb infection and disease status. In vitro stimulation of PBMC
      with Mtb antigens demonstrated that PD-1 is induced on proliferating Mtb-specific
      CD4 T cells and that Th1 cytokine production capacity is preferentially
      maintained within PD-1+ proliferating CD4 T cells, compared with proliferating
      Mtb-specific CD4 T cells that lack PD-1 expression. Together, these data indicate
      that expression of PD-1 on Mtb-specific CD4 T cells is indicative of
      mycobacterial antigen exposure and identifies a population of effector cells with
      Th1 cytokine production capacity. These studies provide novel insights into the
      role of the PD-1 pathway in regulating CD4 and CD8 T cell responses in Mtb
      infection and provide rationale for future studies to evaluate PD-1 expression on
      antigen-specific CD4 T cells as a potential biomarker for bacterial load and
      treatment response in human TB.

PMID- 30233589
TI  - The Role of Collectins and Galectins in Lung Innate Immune Defense.
AB  - Different families of endogenous lectins use complementary defense strategies
      against pathogens. They may recognize non-self glycans typically found on
      pathogens and/or host glycans. The collectin and galectin families are prominent
      examples of these two lectin categories. Collectins are C-type lectins that
      contain a carbohydrate recognition domain and a collagen-like domain. Members of
      this group include surfactant protein A (SP-A) and D (SP-D), secreted by the
      alveolar epithelium to the alveolar fluid. Lung collectins bind to several
      microorganisms, which results in pathogen aggregation and/or killing, and
      enhances phagocytosis of pathogens by alveolar macrophages. Moreover, SP-A and SP
      D influence macrophage responses, contributing to resolution of inflammation, and
      SP-A is essential for tissue-repair functions of macrophages. Galectins also
      function by interacting directly with pathogens or by modulating the immune
      system in response to the infection. Direct binding may result in enhanced or
      impaired infection of target cells, or can have microbicidal effects.
      Immunomodulatory effects of galectins include recruitment of immune cells to the
      site of infection, promotion of neutrophil function, and stimulation of the
      bactericidal activity of infected macrophages. Moreover, intracellular galectins
      can serve as danger receptors, promoting autophagy of the invading pathogen. This
      review will focus on the role of collectins and galectins in pathogen clearance
      and immune response activation in infectious diseases of the respiratory system.

PMID- 30233592
TI  - Hematopoietic Stem/Progenitor Cell Dependent Participation of Innate Lymphoid
      Cells in Low-Intensity Sterile Inflammation.
AB  - Hematopoietic stem/progenitor cells (HSPC) are characterized by their unique
      capacities of self-renewal and multi-differentiation potential. This second
      property makes them able to adapt their differentiation profile depending on the
      local environment they reach. Taking advantage of an animal model of peritonitis,
      induced by injection of the TLR-2 ligand, zymosan, we sought to study the
      relationship between bone marrow-derived hematopoietic stem/progenitor cells (BM
      HSPCs) and innate lymphoid cells (ILCs) regarding their emergence and
      differentiation at the site of inflammation. Our results demonstrate that the
      strength of the inflammatory signals affects the capacity of BM-derived HSPCs to
      migrate and give rise in situ to ILCs. Both low- and high-dose of zymosan
      injections trigger the appearance of mature ILCs in the peritoneal cavity where
      the inflammation occurs. Herein, we show that only in low-dose injected mice, the
      recovered ILCs are dependent on an in situ differentiation of BM-derived HSPCs
      and/or ILC2 precursors (ILC2P) wherein high-dose, the stronger inflammatory
      environment seems to be able to induce the emergence of ILCs independently of BM
      derived HSPCs. We suggest that a relationship between HSPCs and ILCs seems to be
      affected by the strength of the inflammatory stimuli opening new perspectives in
      the manipulation of these early hematopoietic cells.

PMID- 30233590
TI  - Regulatory Mechanisms of IL-33-ST2-Mediated Allergic Inflammation.
AB  - Interleukin-33 (IL-33) plays multiple roles in tissue homeostasis, prevention of
      parasitic infection, and induction of allergic inflammation. Especially, IL-33
      ST2 (IL-1RL1) axis has been regarded as the villain in allergic diseases such as
      asthma and atopic dermatitis and in autoimmune diseases such as rheumatoid
      arthritis. Indeed, a number of studies have indicated that IL-33 produced by
      endothelial cells and epithelial cells plays a critical role in the activation
      and expansion of group 2 innate lymphoid cells (ILC2s) which cause allergic
      inflammation by producing large amounts of IL-5 and IL-13. However, mechanisms
      that antagonize IL-33-ST2-mediated allergic responses remain largely unknown.
      Recently, several groups including our group have demonstrated cellular and
      molecular mechanisms that could suppress excessive activation of ILC2s by the IL
      33-ST2 axis. In this review, we summarize recent progress in the regulatory
      mechanisms of IL-33-ST2-mediated allergic responses. Selective targeting of the
      IL-33-ST2 axis would be a promising strategy in the treatment of allergic
      diseases.

PMID- 30233594
TI  - HLA-Epitope Matching or Eplet Risk Stratification: The Devil Is in the Details.
AB  - "Epitope matching" became a trending topic in organ transplantation. In fact,
      discussions on clinical implementation and utilization of this approach in organ
      allocation algorithms are currently on-going. More recently, the term "eplet
      mismatch load" was introduced in publications. While the terms are often used
      synonymously, they are NOT equivalent. This short overview is meant to emphasize
      the differences between the terms epitope matching and eplet mismatching (or
      mismatch load) as well as to provide perspective on different approaches for
      interpretation of immune compatibility between the donor of an organ transplant
      and the recipient. It highlights some of the less explored qualities of HLA
      epitopes, and stresses the need to understand the differences between donor and
      recipient in terms of immunogenicity and ability to initiate an immune response.
      While the field of "epitope matching" shows enormous promise, it is still in its
      infancy. What is sorely missing is understanding of EPITOPE COMPATIBILITY rather
      than matching. Further work is required before new approaches can be introduced
      into routine clinical practice and organ allocation schemes.

PMID- 30233593
TI  - Oxygen Saturation on Admission Is a Predictive Biomarker for PD-L1 Expression on
      Circulating Monocytes and Impaired Immune Response in Patients With Sepsis.
AB  - Sepsis is a pathology in which patients suffer from a proinflammatory response
      and a dysregulated immune response, including T cell exhaustion. A number of
      therapeutic strategies to treat human sepsis, which are different from
      antimicrobial and fluid resuscitation treatments, have failed in clinical trials,
      and solid biomarkers for sepsis are still lacking. Herein, we classified 85
      patients with sepsis into two groups according to their blood oxygen saturation
      (SaO2): group I (SaO2 <= 92%, n = 42) and group II (SaO2 > 92%, n = 43). Blood
      samples were taken before any treatment, and the immune response after ex vivo
      LPS challenge was analyzed, as well as basal expression of PD-L1 on monocytes and
      levels of sPD-L1 in sera. The patients were followed up for 1 month. Taking into
      account reinfection and exitus frequency, a significantly poorer evolution was
      observed in patients from group I. The analysis of HLA-DR expression on
      monocytes, T cell proliferation and cytokine profile after ex vivo LPS
      stimulation confirmed an impaired immune response in group I. In addition, these
      patients showed both, high levels of PD-L1 on monocytes and sPD-L1 in serum,
      resulting in a down-regulation of the adaptive response. A blocking assay using
      an anti-PD-1 antibody reverted the impaired response. Our data indicated that
      SaO2 levels on admission have emerged as a potential signature for immune status,
      including PD-L1 expression. An anti-PD-1 therapy could restore the T cell
      response in hypoxemic sepsis patients with SaO2 <= 92% and high PD-L1 levels.

PMID- 30233591
TI  - Eicosanoid Control Over Antigen Presenting Cells in Asthma.
AB  - Asthma is a common lung disease affecting 300 million people worldwide. Allergic
      asthma is recognized as a prototypical Th2 disorder, orchestrated by an aberrant
      adaptive CD4+ T helper (Th2/Th17) cell immune response against airborne
      allergens, that leads to eosinophilic inflammation, reversible
      bronchoconstriction, and mucus overproduction. Other forms of asthma are
      controlled by an eosinophil-rich innate ILC2 response driven by epithelial
      damage, whereas in some patients with more neutrophilia, the disease is driven by
      Th17 cells. Dendritic cells (DCs) and macrophages are crucial regulators of type
      2 immunity in asthma. Numerous lipid mediators including the eicosanoids
      prostaglandins and leukotrienes influence key functions of these cells, leading
      to either pro- or anti-inflammatory effects on disease outcome. In this review,
      we will discuss how eicosanoids affect the functions of DCs and macrophages in
      the asthmatic lung and how this leads to aberrant T cell differentiation that
      causes disease.

PMID- 30233596
TI  - Trimetazidine Attenuates Cardiac Dysfunction in Endotoxemia and Sepsis by
      Promoting Neutrophil Migration.
AB  - Aims: Cardiac dysfunction can be a fatal complication during severe sepsis. The
      migration of neutrophils is significantly impaired during severe sepsis. We
      sought to determine the role of trimetazidine (TMZ) in regulation of neutrophil
      migration to the heart in a mouse model of sepsis and endotoxemia, and to
      identify the mechanism whereby TMZ confers a survival advantage. Methods and
      Results: C57/BL6 mice were (1) injected with LPS followed by 24-h TMZ
      administration, or (2) treated with TMZ (20 mg/kg/day) for 1 week post cecal
      ligation and puncture (CLP) operation. Echocardiography and Millar system
      detection showed that TMZ alleviated cardiac dysfunction and histological
      staining showed the failure of neutrophils migration to heart in both LPS- and
      CLP-induced mice. Bone marrow transplantation revealed that TMZ-pretreated bone
      marrow cells improved LPS- and CLP-induced myocardial dysfunction and enhanced
      neutrophil recruitment in heart. In CXCL2-mediated chemotaxis assays, TMZ
      increased neutrophils migration via AMPK/Nrf2-dependent up-regulation of CXCR2
      and inhibition of GRK2. Furthermore, using luciferase reporter gene and chromatin
      immunoprecipitation assays, we found that TMZ promoted the binding of the Nrf2
      and CXCR2 promoter regions directly. Application of CXCR2 inhibitor completely
      reversed the protective effects of TMZ in vivo. Co-culture of neutrophils and
      cardiomyocytes further validated that TMZ decreased LPS-induced cardiomyocyte
      pyroptosis by targeting neutrophils. Conclusion: Our findings suggested TMZ as a
      potential therapeutic agent for septic or endotoxemia associated cardiac
      dysfunction in mice. STUDY HIGHLIGHTS  What is the current knowledge on the
      topic? Migration of neutrophils is significantly impaired during severe sepsis,
      but the underlying mechanisms remain unknown. What question did this study
      address? The effects of TMZ on cardiac dysfunction via neutrophils migration.
      What this study adds to our knowledge TMZ attenuated LPS-induced cardiomyocyte
      pyroptosis and cardiac dysfunction by promoting neutrophils recruitment to the
      heart tissues via CXCR2. How this might change clinical pharmacology or
      translational science Our findings suggested TMZ as a potential therapeutic agent
      for septic cardiac dysfunction.

PMID- 30233595
TI  - The -3279C>A and -924A>G polymorphisms in the FOXP3 Gene Are Associated With
      Viral Load and Liver Enzyme Levels in Patients With Chronic Viral Liver Diseases.
AB  - The transcription factor FOXP3 is an essential marker of the development and
      activation of regulatory T cells (Tregs), which are cells specialized in the
      regulation and normal tolerance of the immune response. In the context of chronic
      viral liver diseases, Tregs participate in the maintenance of infections by
      promoting histopathological control and favor the immune escape of viral agents
      by suppressing the antiviral response. Single nucleotide polymorphisms (SNPs) may
      influence the function of FOXP3 in a number of pathological conditions. The
      present study sought to evaluate the influence of SNPs in the FOXP3 gene promoter
      region in patients with chronic viral liver diseases. Three SNPs (-3279C>A, 
      2383C>T, and -924A>G) were analyzed in groups of patients with chronic hepatitis
      C (CHC), active chronic hepatitis B (CHB-A), inactive chronic hepatitis B (CHB
      I), and a healthy control group (CG) using real-time PCR. The frequencies of the
      polymorphic variants were compared between groups and correlated with liver
      histopathological characteristics and enzyme levels [i.e., alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl
      transpeptidase (GGT)] obtained via biopsy and from the clinical records of the
      participating patients, respectively. For the -2338C>T SNP, no significant
      differences were found in the frequencies of variants between groups or in the
      histological findings. Significant associations between the polymorphisms and the
      CHB-I group were not established. The -3279C>A SNP was associated with altered
      viral loads (log10) and GGT levels in CHC patients with advanced stages of
      inflammatory activity and liver fibrosis. The -924A>G SNP was associated with
      altered viral loads (log10) and liver enzyme levels among CHB-A patients with
      milder inflammation and fibrosis. However, the frequencies of the -3279C>A and 
      924A>G polymorphisms were not directly associated with the histopathological
      profiles of the analyzed patients. These polymorphic variants may influence
      hepatic function in patients with chronic viral liver diseases but are not
      directly associated with the establishment of the degree of inflammatory activity
      and liver fibrosis.

PMID- 30233597
TI  - Fra2 Overexpression in Mice Leads to Non-allergic Asthma Development in an IL-13
      Dependent Manner.
AB  - Background: Asthma is a complex chronic inflammatory disease characterised by
      airway inflammation, remodelling and hyperresponsiveness (AHR). Members of the AP
      1 transcription factor family play important roles in the activation of the
      immune system and the control of cellular responses; however, their role in the
      development of asthma has not been well studied. We aimed to investigate the role
      of the lesser known AP-1 family member, Fra2 in experimental asthma. Methods:
      Phenotypic characterisation and gene expression profiling was performed on Fra2
      (TG) overexpressing and wild-type mice. The efficacy of therapeutic interventions
      in regulating the Fra2 phenotype was determined. Results: Transcriptional
      profiling of TG mice revealed a high abundance of regulated genes associated with
      airway remodelling, inflammation and mucus production. A concomitant increase in
      peribronchial collagen deposition, smooth muscle thickening and mucus production
      was observed. TG mice possessed increased inflammatory infiltration in the lung,
      predominantly consisting of eosinophils and T-cells and elevated expression of
      Th2 cytokines and eotaxin. Furthermore, TG mice possessed severe AHR in response
      to increasing doses of methacholine. Glucocorticoid treatment led to a partial
      improvement of the asthma phenotype, whereas blockade of IL-13 via neutralising
      antibodies ameliorated AHR and mucus production, but had no effect on collagen
      deposition. Conclusion: We here describe a novel model for non-allergic asthma
      that does not require the application of exogenous allergens, which mimics
      several key features of the disease, such as airway inflammation, remodelling and
      hyperresponsiveness. Fra2 may represent a key molecule coordinating multiple
      aspects of asthma pathogenesis.

PMID- 30233598
TI  - Cytosolic Internalization of Anti-DNA Antibodies by Human Monocytes Induces
      Production of Pro-inflammatory Cytokines Independently of the Tripartite Motif
      Containing 21 (TRIM21)-Mediated Pathway.
AB  - Anti-DNA autoantibodies are a hallmark of systemic lupus erythematosus (SLE). A
      subset of anti-DNA IgG autoantibodies is cell-internalizable; thus they can enter
      living cells in the form of free IgG. However, the contribution made by the Fc
      region of internalized free-form IgG to the cytokine response has not been
      studied, despite the recent discovery of tripartite motif-containing 21 (TRIM21),
      a cytosolic Fc receptor involved in immune signaling. This study used an
      internalizable IgG anti-DNA antibody (3D8) to examine the cytokine responses of
      human monocytes to the Fc region of cytosolic free IgG. Internalization of 3D8
      IgG and a 3D8 single-chain variable fragment-Fc (scFv-Fc) induced production of
      IL-8 and TNF-alpha via activation of NF-kappaB. By contrast, a 3D8 scFv
      (comprising variable domains alone) did not. This suggests Fc-dependent cytokine
      signaling. A 3D8 IgG-N434D mutant that is not recognized by TRIM21 induced
      greater production of cytokines than 3D8 IgG. Moreover the amounts of cytokines
      induced by 3D8 IgG in TRIM21-knockdown THP-1 cells were higher than those in
      control cells, indicating that cytokine signaling is not mediated by TRIM21. The
      results suggest the existence of a novel Fc-dependent signaling pathway that is
      activated upon internalization of IgG antibodies by human monocytes.

PMID- 30233600
TI  - Commentary: Immune System Dysregulation During Spaceflight: Potential
      Countermeasures for Deep Space Exploration Missions.

PMID- 30233599
TI  - A Type I Interferon and IL-10 Induced by Orientia tsutsugamushi Infection
      Suppresses Antigen-Specific T Cells and Their Memory Responses.
AB  - Despite the various roles of type I interferon (type I IFN) responses during
      bacterial infection, its specific effects in vivo have been poorly characterized
      in scrub typhus caused by Orientia tsutsugamushi infection. Here, we show that
      type I IFNs are primarily induced via intracellular nucleic acids sensors,
      including RIG-I/MAVS and cGAS/STING pathways, during O. tsutsugamushi invasion.
      However, type I IFN signaling did not significantly affect pathogenesis,
      mortality, or bacterial burden during primary infection in vivo, when assessed in
      a mice model lacking a receptor for type I IFNs (IFNAR KO). Rather, it
      significantly impaired the induction of antigen-specific T cells and reduced
      memory T cell responses. IFNAR KO mice that recovered from primary infection
      showed stronger antigen-specific T cell responses, especially Th1, and more
      efficiently controlled bacteremia during secondary infection than wild type mice.
      Enhanced IL-10 expression by macrophages in the presence of type I IFN signaling
      might play a significant role in the suppression of antigen-specific T cell
      responses as neutralization or knock-out (KO) of IL-10 increased T cell responses
      in vitro. Therefore, induction of the type I IFN/IL-10 axis by O. tsutsugamushi
      infection might play a significant role in the suppression of T cell responses
      and contribute to the short longevity of cell-mediated immunity, often observed
      in scrub typhus patients.

PMID- 30233602
TI  - Transcriptome Analysis of Poplar Under Salt Stress and Over-Expression of
      Transcription Factor NAC57 Gene Confers Salt Tolerance in Transgenic Arabidopsis.
AB  - NAC domain genes belong to a large plant-specific transcription factor family,
      which is well-known to be associated with multiple stress responses and plant
      developmental processes. In this study, we screened differentially expressed
      genes (DEGs) and detected mRNA abundance of NAC family by RNA-Seq in the poplar
      leaves under salt stress condition. A total of 276 up-regulated DEGs and 159 down
      regulated DEGs were identified to be shared in Populus alba * Populus glandulosa
      and Populus simonii * Populus nigra. Among 170 NAC members, NAC57 gene was
      significantly up-regulated in response to salt stress in the two species. Tissue
      specific and salt-responsive analyses indicated the expression pattern of NAC57
      gene was spatial and temporal in poplar under salt stress. Particle bombardment
      results showed subcellular localization of NAC57 was not solely nucleus-targeted.
      Full-length cDNA sequence of the NAC57 gene was cloned from P. alba * P.
      glandulosa and transformed into Arabidopsis thaliana. Under salt stress,
      transgenic Arabidopsis overexpressing NAC57 showed higher seed germination rate,
      root length, and fresh weight than wild type plants. In addition, the transgenic
      plants displayed higher superoxide dismutase activity and peroxidase activity,
      and lower malondialdehyde content and relative electrical conductivity than the
      wild type under salt stress condition. Furthermore, histochemical staining
      indicated reactive oxygen species accumulation was lower in the transgenic plants
      than that in the wild type under salt stress. All the results indicated that the
      NAC57 gene plays an important role in salt stress responses.

PMID- 30233601
TI  - The Transcriptional Regulation of Germinal Center Formation.
AB  - Germinal centers (GCs) are essential structures of the humoral immune response,
      which form in the periphery in response to T cell dependent antigens. During the
      GC reaction, B cells undergo critical differentiation steps, which ultimately
      lead to the generation of antibodies with altered effector function and higher
      affinity for the selected antigen. Remarkably, many of the B cell tumors have
      their origin in the GCs; thus, understanding how the formation of these
      structures is regulated or deregulated is of high medical importance. This review
      gives an overview of the transcription factors that have been linked to the
      generation of GCs, and of their roles in the process.

PMID- 30233604
TI  - A Review of Relative Pollen Productivity Estimates From Temperate China for
      Pollen-Based Quantitative Reconstruction of Past Plant Cover.
AB  - Model-based quantitative reconstruction of past plant cover in Europe has shown
      great potential for: (i) testing hypotheses related to Holocene vegetation
      dynamics, biodiversity, and their relationships with climate and land use; (ii)
      studying long term interactions between climate and land use. Similar model-based
      quantitative reconstruction of plant cover in China has been restricted due to
      the lack of standardized datasets of existing estimates of relative pollen
      productivity (RPP). This study presents the first synthesis of all RPP values
      available to date for 39 major plant taxa from temperate China and proposes
      standardized RPP datasets that can be used for model-based quantitative
      reconstructions of past plant cover using fossil pollen records for the region.
      We review 11 RPP studies in temperate China based on modern pollen and related
      vegetation data around the pollen samples. The study areas include meadow, steppe
      and desert vegetation, various woodland types, and cultural landscapes. We
      evaluate the strategies of each study in terms of selection of study areas and
      distribution of study sites; pollen- and vegetation-data collection in field;
      vegetation-data collection from satellite images and vegetation maps; and data
      analysis. We compare all available RPP estimates, select values based on precise
      rules and calculate mean RPP estimates. We propose two standardized RPP datasets
      for 31 (Alt1) and 29 (Alt2) plant taxa. The ranking of mean RPPs (Alt-2) relative
      to Poaceae (= 1) for eight major taxa is: Artemisia (21) > Pinus (18.4) > Betula
      (12.5) > Castanea (11.5) > Elaeagnaceae (8.8) > Juglans (7.5) > Compositae (4.5)
      > Amaranthaceae/Chenopodiaceae (4). We conclude that although RPPs are comparable
      between Europe and China for some genera and families, they can differ very
      significantly, e.g., Artemisia, Compositae, and Amaranthaceae/Chenopodiaceae. For
      some taxa, we present the first RPP estimates e.g. Castanea, Elaeagnaceae, and
      Juglans. The proposed standardized RPP datasets are essential for model-based
      reconstructions of past plant cover using fossil pollen records from temperate
      China.

PMID- 30233603
TI  - Whole Genome Characterization of a Few EMS-Induced Mutants of Upland Rice Variety
      Nagina 22 Reveals a Staggeringly High Frequency of SNPs Which Show High
      Phenotypic Plasticity Towards the Wild-Type.
AB  - The Indian initiative, in creating mutant resources for the functional genomics
      in rice, has been instrumental in the development of 87,000 ethylmethanesulfonate
      (EMS)-induced mutants, of which 7,000 are in advanced generations. The mutants
      have been created in the background of Nagina 22, a popular drought- and heat
      tolerant upland cultivar. As it is a pregreen revolution cultivar, as many as 573
      dwarf mutants identified from this resource could be useful as an alternate
      source of dwarfing. A total of 541 mutants, including the macromutants and the
      trait-specific ones, obtained after appropriate screening, are being maintained
      in the mutant garden. Here, we report on the detailed characterizations of the
      541 mutants based on the distinctness, uniformity, and stability (DUS)
      descriptors at two different locations. About 90% of the mutants were found to be
      similar to the wild type (WT) with high similarity index (>0.6) at both the
      locations. All 541 mutants were characterized for chlorophyll and epicuticular
      wax contents, while a subset of 84 mutants were characterized for their ionomes,
      namely, phosphorous, silicon, and chloride contents. Genotyping of these mutants
      with 54 genomewide simple sequence repeat (SSR) markers revealed 93% of the
      mutants to be either completely identical to WT or nearly identical with just one
      polymorphic locus. Whole genome resequencing (WGS) of four mutants, which have
      minimal differences in the SSR fingerprint pattern and DUS characters from the
      WT, revealed a staggeringly high number of single nucleotide polymorphisms (SNPs)
      on an average (16,453 per mutant) in the genic sequences. Of these, nearly 50% of
      the SNPs led to non-synonymous codons, while 30% resulted in synonymous codons.
      The number of insertions and deletions (InDels) varied from 898 to 2,595, with
      more than 80% of them being 1-2 bp long. Such a high number of SNPs could pose a
      serious challenge in identifying gene(s) governing the mutant phenotype by next
      generation sequencing-based mapping approaches such as Mutmap. From the WGS data
      of the WT and the mutants, we developed a genic resource of the WT with a novel
      analysis pipeline. The entire information about this resource along with the
      panicle architecture of the 493 mutants is made available in a mutant database
      EMSgardeN22 (http://14.139.229.201/EMSgardeN22).

PMID- 30233605
TI  - Genome Wide Association Mapping of Grain and Straw Biomass Traits in the Rice
      Bengal and Assam Aus Panel (BAAP) Grown Under Alternate Wetting and Drying and
      Permanently Flooded Irrigation.
AB  - Growing demand for staple crops like rice will need to be achieved predominately
      through agricultural intensification and more efficient use of inputs. To meet
      this demand it is essential that the genetic diversity within rice is fully
      utilized. The aus subpopulation is considered an underappreciated resource within
      that diversity. A new rice panel, the Bengal and Assam Aus Panel (BAAP) of 266
      aus accessions was generated with ~2 million informative SNPs obtained using skim
      sequencing at ~4* depth. The BAAP was grown in the field in Bangladesh in the
      'boro' season under both continuously flooded and Alternate Wetting and Drying
      (AWD) irrigation during 2013 and 2014 in Mymensingh and during 2014 in Madhupur.
      Heading date, grain mass, straw biomass and harvest index were measured. The
      majority (94%) of BAAP accessions flowered within a relatively small window of 10
      days. The AWD irrigation treatment generally caused an increase in grain mass,
      but no significant genotype by treatment interactions were detected for this
      trait. Shoot biomass was the only trait that showed evidence of genotype by
      treatment interaction. The average LD (Linkage Disequilibrium) decay across the
      genome was 243 Kbp. Genome wide association mapping revealed 115 quantitative
      trait loci (QTLs). There was little evidence of QTLs specific to the irrigation
      treatment, and only a few QTLs co-localized with known genes. However, some QTLs
      were detected across multiple sites and years. These QTLs should be targets for
      breeding, and include a region around 2.2 Mbp on chromosome 1, a large region in
      the middle of chromosome 7 and two regions on chromosome 11 (~10 Mbp and ~29
      Mbp). The BAAP appears to be a valuable addition to the growing collection of GWA
      mapping populations of rice.

PMID- 30233606
TI  - BABA-Primed Histone Modifications in Potato for Intergenerational Resistance to
      Phytophthora infestans.
AB  - In this paper we analyzed beta-aminobutyric acid (BABA)-primed epigenetic
      adjustment of potato cv. "Sarpo Mira" to Phytophthora infestans. The first stress
      free generation of the potato genotype obtained from BABA-primed parent plants
      via tubers and seeds showed pronounced resistance to the pathogen, which was
      tuned with the transcriptional memory of SA-responsive genes. During the early
      priming phase before the triggering stress, we found robust bistable deposition
      of histone marks (H3K4me2 and H3K27me3) on the NPR1 (Non-expressor of PR genes)
      and the SNI1 gene (Suppressor of NPR1, Inducible), in which transcription
      antagonized silencing. Switchable chromatin states of these adverse systemic
      acquired resistance (SAR) regulators probably reprogrammed responsiveness of the
      PR1 and PR2 genes and contributed to stress imprinting. The elevated levels of
      heritable H3K4me2 tag in the absence of transcription on SA-dependent genes in
      BABA-primed (F0) and its vegetative and generative progeny (F1) before pathogen
      challenge provided evidence for the epigenetic mark for intergenerational memory
      in potato. Moreover, our study revealed that histone acetylation was not critical
      for maintaining BABA-primed defense information until the plants were triggered
      with the virulent pathogen when rapid and boosted PRs gene expression probably
      required histone acetyltransferase (HAT) activity both in F0 and F1 progeny.

PMID- 30233607
TI  - Forward Genetics Approach Reveals a Mutation in bHLH Transcription Factor
      Encoding Gene as the Best Candidate for the Root Hairless Phenotype in Barley.
AB  - Root hairs are the part of root architecture contributing significantly to the
      root surface area. Their role is particularly substantial in maintaining plant
      growth under stress conditions, however, knowledge on mechanism of root hair
      differentiation is still limited for majority of crop species, including barley.
      Here, we report the results of a map-based identification of a candidate gene
      responsible for the lack of root epidermal cell differentiation, which results in
      the lack of root hairs in barley. The analysis was based on the root hairless
      barley mutant rhl1.b, obtained after chemical mutagenesis of spring cultivar
      'Karat'. The rhl1 gene was located in chromosome 7HS in our previous studies.
      Fine mapping allowed to narrow the interval encompassing rhl1 gene to 3.7 cM,
      which on physical barley map spans a region of 577 kb. Five high confidence genes
      are located within this region and their sequencing resulted in the
      identification of A>T mutation in one candidate, HORVU7Hr1G030250 (MLOC_38567),
      differing the mutant from its parent variety. The mutation, located in the 3'
      splice-junction site, caused the retention of the last intron, 98 bp long, in
      mRNA of rhl1.b allele. This resulted in the frameshift, the synthesis of 71
      abnormal amino acids and introduction of premature STOP codon in mRNA. The
      mutation was present in the recombinants from the mapping population (F2rhl1.b *
      'Morex') that lacked root hairs. The candidate gene encodes a bHLH transcription
      factor with LRL domain and may be involved in early stages of root hair cell
      development. We discuss the possible involvement of HORVU7Hr1G030250 in this
      process, as the best candidate responsible for early stages of rhizodermis
      differentiation in barley.

PMID- 30233608
TI  - Bacteria and Competing Herbivores Weaken Top-Down and Bottom-Up Aphid
      Suppression.
AB  - Herbivore suppression is mediated by both plant defenses and predators. In turn,
      plant defenses are impacted by soil fertility and interactions with soil
      bacteria. Measuring the relative importance of nutritional and microbial drivers
      of herbivore resistance has proven problematic, in part because it is difficult
      to manipulate soil-bacterial community composition. Here, we exploit variation in
      soil fertility and microbial biodiversity across 20 farms to untangle suppression
      of aphids (Brevicoryne brassicae) through bottom-up and top-down channels. We
      planted Brassica oleracea plants in soil from each farm, manipulated single and
      dual infestations of aphids alone or with caterpillars (Pieris rapae), and
      exposed aphids to parasitoid wasps (Diaeretiella rapae) in the open field. We
      then used multi-model inference to identify the strongest soil-based predictors
      of herbivore growth and parasitism. We found that densities of Bacillus spp., a
      genus known to include plant-growth-promoting rhizobacteria, negatively
      correlated with aphid suppression by specialist parasitoids. Aphid parasitism
      also was disrupted on plants that had caterpillar damage, compared to plants
      attacked only by aphids. Relative abundance of Pseudomonas spp. bacteria
      correlated with higher aphid growth, although this appeared to be a direct
      effect, as aphid parasitism was not associated with this group of bacteria. Non
      pathogenic soil bacteria are often shown to deliver benefits to plants, improving
      plant nutrition and the deployment of anti-herbivore defenses. However, our
      results suggest that these plant growth-promoting bacteria may also indirectly
      weaken top-down aphid suppression by parasitoids and directly improve aphid
      performance. Against a background of varying soil fertility, microbial
      biodiversity, competing herbivores, and natural enemies, we found that effects of
      non-pathogenic soil microbes on aphid growth outweighed those of nutritional
      factors. Therefore, predictions about the strength of plant defenses along
      resource gradients must be expanded to include microbial associates.

PMID- 30233609
TI  - Nectar Replaced by Volatile Secretion: A Potential New Role for Nectarless
      Flowers in a Bee-Pollinated Plant Species.
AB  - The presence of nectarless flowers in nectariferous plants is a widespread
      phenomenon in angiosperms. However, the frequency and distribution of nectarless
      flowers in natural populations, and the transition from nectariferous to
      nectarless flowers are poorly known. Variation in nectar production may affect
      mutualism stability, since energetic resource availability influences
      pollinators' foraging behavior. Here, we described the spatial and temporal
      nectar production patterns of Jacaranda oxyphylla, a bee-pollinated species that
      naturally presents nectarless flowers. Additionally, we compared nectariferous
      and nectarless floral disks in order to identify histological, subcellular and
      chemical changes that accompanied the loss of nectar production ability. For that
      we used standard methods for light and transmission electron microscopy, and gas
      chromatography coupled to mass spectrometry for chemical analyses. We verified
      that 47% of flowers did not produce nectar during the whole flower lifespan
      (nectarless flowers). We also observed remarkable inter-plant variation, with
      individuals having only nectarless flowers, others only nectariferous ones and
      most of them showing different proportions of both flower types, with variable
      nectar volumes (3-21 MUl). Additionally, among nectariferous flowers, we
      registered two distinct rhythms of nectar production. 'Early' flowers produced
      nectar from 0 to 24 h, and 'late' flowers produced nectar from 24 to 48 h of
      anthesis. Although disks from nectariferous and nectarless flowers displayed
      similar histological organization, they differed strongly at subcellular level.
      Nectariferous ('early' and 'late') flowers exhibited a cellular apparatus typical
      of nectar secretion, while nectarless flowers exhibited osmophoric features. We
      found three aliphatic and one aromatic compound(s) that were detected in both the
      headspace of flowers and the disks of nectarless flowers, but not the disks of
      nectariferous flowers Although the remarkable variation in nectar availability
      may discourage pollinator visits, nectarless flowers might compensate it by
      producing volatile compounds that can be part of floral scent, acting as chemical
      attractants. Thus, nectarless flowers may be helping to maintain pollination in
      this scenario of trophic resource supply scarcity. We suggest that J. oxyphylla
      can be transitioning from a nectar-based pollination system to another resource
      based or even to a deceit mechanism of pollination.

PMID- 30233610
TI  - Direct Determination of the Site of Addition of Glucosyl Units to
      Maltooligosaccharide Acceptors Catalyzed by Maize Starch Synthase I.
AB  - Starch synthase (SS) (ADP-glucose:1,4-alpha-D-glucan 4-alpha-D
      glucosyltransferase) elongates alpha-(1->4)-linked linear glucans within plastids
      to generate the storage polymers that constitute starch granules. Multiple SS
      classes are conserved throughout the plant kingdom, indicating that each provides
      a unique function responsible for evolutionary selection. Evidence has been
      presented arguing for addition of glucosyl units from the ADPglucose donor to
      either the reducing end or the non-reducing end of the acceptor substrate,
      although until recently direct evidence addressing this question was not
      available. Characterization of newly incorporated glucosyl units determined that
      recombinant maize (Zea mays L.) SSIIa elongates its substrates at the non
      reducing end. However, the possibility remained that other SSs might utilize
      distinct mechanisms, and that one or more of the conserved enzyme classes could
      elongate acceptors at the reducing end. This study characterized the reaction
      mechanism of recombinant maize SSI regarding its addition site. Newly
      incorporated residues were labeled with 13C, and reducing ends of the elongation
      products were labeled by chemical derivitization. Electrospray ionization-tandem
      mass spectroscopy traced the two parameters, i.e., the newly added residue and
      the reducing end. The results determined that SSI elongates glucans at the non
      reducing end. The study also confirmed previous findings showing recombinant SSI
      can generate glucans of at least 25 units, that it is active using acceptors as
      short as maltotriose, that recombinant forms of the enzyme absolutely require an
      acceptor for activity, and that it is not saturable with maltooligosaccharide
      acceptor substrates.

PMID- 30233612
TI  - QTL Mapping of Fusarium Head Blight and Correlated Agromorphological Traits in an
      Elite Barley Cultivar Rasmusson.
AB  - Fusarium head blight (FHB) is an important fungal disease affecting the yield and
      quality of barley and other small grains. Developing and deploying resistant
      barley cultivars is an essential component of an integrated strategy for reducing
      the adverse effects of FHB. Genetic mapping studies have revealed that resistance
      to FHB and the accumulation of pathogen-produced mycotoxins are controlled by
      many quantitative trait loci (QTL) with minor effects and are highly influenced
      by plant morphological traits and environmental conditions. Some prior studies
      aimed at mapping FHB resistance have used populations derived from crossing a
      Swiss landrace Chevron with elite breeding lines/cultivars. Both Chevron and
      Peatland, a sib-line of Chevron, were used as founders in the University of
      Minnesota barley breeding program. To understand the native resistance that might
      be present in the Minnesota breeding materials, a cross of an elite cultivar with
      a susceptible unadapted genotype is required. Here, a mapping population of 93
      recombinant inbred lines (RILs) was developed from a cross between a moderately
      susceptible elite cultivar 'Rasmusson' and a highly susceptible Japanese landrace
      PI 383933. This population was evaluated for FHB severity, deoxynivalenol (DON)
      accumulation and various agromorphological traits. Genotyping of the population
      was performed with the barley iSelect 9K SNP chip and 1,394 SNPs were used to
      develop a genetic map. FHB severity and DON accumulation were negatively
      correlated with plant height (HT) and spike length (SL), and positively
      correlated with spike density (SD). QTL analysis using composite interval mapping
      (CIM) identified the largest effect QTL associated with FHB and DON on the
      centromeric region of chromosome 7H, which was also associated with HT, SL, and
      SD. A minor FHB QTL and a minor DON QTL were detected on chromosome 6H and
      chromosome 3H, respectively, and the Rasmusson alleles contributed to resistance.
      The 3H DON QTL likely represents native resistance in elite germplasm as the
      marker haplotype of Rasmusson at this QTL is distinct from that of Chevron. This
      study highlights the relationship between FHB resistance/susceptibility and
      morphological traits and the need for breeders to account for morphology when
      developing FHB resistant genotypes.

PMID- 30233611
TI  - Combinations of Abiotic Factors Differentially Alter Production of Plant
      Secondary Metabolites in Five Woody Plant Species in the Boreal-Temperate
      Transition Zone.

PMID- 30233613
TI  - Competitive Effects Hinder the Recolonization of Native Species in Environments
      Densely Occupied by One Invasive Exotic Species.
AB  - The responses of native plants to competition with invasive plants depend mainly
      on the density of the invasive plants and on the ability of the native plants to
      compete for resources. In this study, we tested the influence of the invasive
      exotic Urochloa arrecta (Poaceae) on the early colonization of two native species
      (Pontederia cordata and Leersia hexandra) of aquatic macrophytes. Our hypotheses
      were (i) the competitive effects of U. arrecta on the native species P. cordata
      and L. hexandra are density-dependent and that (ii) these species respond
      differently to competitive interactions with the invasive species. We conducted
      the experiments in a greenhouse and in the field, in a tropical reservoir. The
      biomass of U. arrecta (ranging from 206.2 to 447.1 g) was manipulated in the
      greenhouse in trays with different densities. After the establishment of the
      invasive species, we added P. cordata and L. hexandra propagules to each tray. In
      the field, a propagule of P. cordata was planted in 36 sites with different
      densities of U. arrecta. The biomass and length of the natives and the biomass of
      the invasive species were measured in the greenhouse and in the field
      experiments. The biomass and length of the native plants decreased with
      increasing biomass of the exotic species in both experiments, showing that the
      competition between U. arrecta and native species depends on the density of the
      exotic species. The root:shoot ratio of L. hexandra decreased with increasing U.
      arrecta biomass, but the opposite occurred for P. cordata. These results indicate
      that native species exhibit different strategies of biomass allocation when
      interacting with U. arrecta. The strong competitive effects of U. arrecta and the
      different responses of the native species help to explain the reduced diversity
      of native macrophytes observed in sites colonized by U. arrecta. The results also
      suggest that in a scenario of dominance of exotic species, recolonization by
      native macrophytes is unlike to occur naturally and without human interventions
      that reduce the biomass of the exotic species.

PMID- 30233614
TI  - Mycorrhizae and Rhizobacteria on Precambrian Rocky Gold Mine Tailings: I. Mine
      Adapted Symbionts Promote White Spruce Health and Growth.
AB  - White spruce [Picea glauca (Moench) Voss] is a commercially valuable boreal tree
      that has been known for its ability to colonize deglaciated rock tailings. Over
      the last decade, there has been an increasing interest in using this species for
      the revegetation and successful restoration of abandoned mine spoils. Herein, we
      conducted a glasshouse experiment to screen mycorrhizal fungi and rhizobacteria
      capable of improving the health and growth of white spruce seedlings growing
      directly on waste rocks (WRs) or fine tailings (FTs) from the Sigma-Lamaque gold
      mine located in the Canadian Abitibi region. After 32 weeks, measurements of
      health, growth, and mycorrhizal colonization variables of seedlings were
      performed. Overall, symbionts isolated from roots of healthy white spruce
      seedlings growing on the mining site, especially Cadophora finlandia Cad. fin.
      MBN0213 GenBank No. KC840625 and Pseudomonas putida MBN0213 GenBank No. AY391278,
      were more efficient in enhancing seedling health and growth than allochthonous
      species and constitute promising microbial symbionts. In general, mycorrhizae
      promoted plant health and belowground development, while rhizobacteria enhanced
      aboveground plant biomass. The observed beneficial effects were substrate-,
      strain-, and/or strains combination-specific. Therefore, preliminary experiments
      in control conditions such as the one described here can be part of an efficient
      and integrated strategy to select ecologically well-adapted symbiotic
      microorganisms, critical for the success of a long-term revegetation program.

PMID- 30233615
TI  - Mycorrhizae and Rhizobacteria on Precambrian Rocky Gold Mine Tailings: II. Mine
      Adapted Symbionts Alleviate Soil Element Imbalance for a Better Nutritional
      Status of White Spruce Seedlings.
AB  - In the context of a phytorestoration project, the purpose of this study was to
      assess the respective contribution to the nutritional status of Picea glauca
      seedlings of ectomycorrhizae and rhizobacteria native or not to the Sigma-Lamaque
      gold mine wastes in northern Quebec, Canada. In a glasshouse experiment,
      inoculated plants were grown for 32 weeks on coarse waste rocks or fine tailings
      obtained from the mining site. The survival, health, growth, and nutritional
      status of plants were better on coarse waste rocks than on fine tailings. Fe and
      Ca were especially found at high levels in plant tissues but at much lower
      concentrations on waste rocks. Interestingly, inoculation of microsymbionts had
      only minimal effects on N, P, K, and Mg plant status that were indeed close or
      within the concentration range encountered in healthy seedlings. However, both
      fungal and bacterial treatments improved Fe and Ca concentrations in plant
      tissues. Fe concentration in the foliage of plants inoculated with the fungi
      Tricholoma scalpturatum Tri. scalp. MBN0213 GenBank #KC840613 and Cadophora
      finlandia Cad. fin. MBN0213 GenBank #KC840625 was reduced by >50%. Both fungi
      were isolated from the mining site. The rhizobacteria, Azotobacter chroococcum,
      also improved plant Fe level in some cases. Regarding Ca nutritional status, the
      native bacterial strain Pseudomonas putida MBN0213 GenBank #AY391278 was the only
      symbiont that reduced foliar content by up to 23%. Ca concentration was
      negatively correlated with the fungal mycorrhization rate of seedling roots. This
      relation was especially strong (r = -0.66, p-value <= 0.0001) in the case of C.
      finlandia. Also, a similar relationship existed with root Fe concentration (r = 
      0.44, p-value <= 0.0001). In fact, results showed that seedling performance was
      more correlated with elevated Ca and Fe concentration in planta than with
      nutrient deficiency. Also, native microsymbionts were capable of regulating
      seedling nutrition in the poor substrate of the Sigma-Lamaque gold mine tailings.

PMID- 30233616
TI  - Beneficial Services of Arbuscular Mycorrhizal Fungi - From Ecology to
      Application.
AB  - Arbuscular mycorrhiza (AM) is the most common symbiotic association of plants
      with microbes. AM fungi occur in the majority of natural habitats and they
      provide a range of important ecological services, in particular by improving
      plant nutrition, stress resistance and tolerance, soil structure and fertility.
      AM fungi also interact with most crop plants including cereals, vegetables, and
      fruit trees, therefore, they receive increasing attention for their potential use
      in sustainable agriculture. Basic research of the past decade has revealed the
      existence of a dedicated recognition and signaling pathway that is required for
      AM. Furthermore, recent evidence provided new insight into the exchange of
      nutritional benefits between the symbiotic partners. The great potential for
      application of AM has given rise to a thriving industry for AM-related products
      for agriculture, horticulture, and landscaping. Here, we discuss new developments
      in these fields, and we highlight future potential and limits toward the use of
      AM fungi for plant production.

PMID- 30233617
TI  - Genome-Wide Association Mapping of Seedling Heat Tolerance in Winter Wheat.
AB  - Heat stress during the seedling stage of early-planted winter wheat (Triticum
      aestivum L.) is one of the most abiotic stresses of the crop restricting forage
      and grain production in the Southern Plains of the United States. To map
      quantitative trait loci (QTLs) and identify single-nucleotide polymorphism (SNP)
      markers associated with seedling heat tolerance, a genome-wide association
      mapping study (GWAS) was conducted using 200 diverse representative lines of the
      hard red winter wheat association mapping panel, which was established by the
      Triticeae Coordinated Agricultural Project (TCAP) and genotyped with the wheat
      iSelect 90K SNP array. The plants were initially planted under optimal
      temperature conditions in two growth chambers. At the three-leaf stage, one
      chamber was set to 40/35 degrees C day/night as heat stress treatment, while the
      other chamber was kept at optimal temperature (25/20 degrees C day/night) as
      control for 14 days. Data were collected on leaf chlorophyll content, shoot
      length, number of leaves per seedling, and seedling recovery after removal of
      heat stress treatment. Phenotypic variability for seedling heat tolerance among
      wheat lines was observed in this study. Using the mixed linear model (MLM), we
      detected multiple significant QTLs for seedling heat tolerance on different
      chromosomes. Some of the QTLs were detected on chromosomes that were previously
      reported to harbor QTLs for heat tolerance during the flowering stage of wheat.
      These results suggest that some heat tolerance QTLs are effective from the
      seedling to reproductive stages in wheat. However, new QTLs that have never been
      reported at the reproductive stage were found responding to seedling heat stress
      in the present study. Candidate gene analysis revealed high sequence similarities
      of some significant loci with candidate genes involved in plant stress responses
      including heat, drought, and salt stress. This study provides valuable
      information about the genetic basis of seedling heat tolerance in wheat. To the
      best of our knowledge, this is the first GWAS to map QTLs associated with
      seedling heat tolerance targeting early planting of dual-purpose winter wheat.
      The SNP markers identified in this study will be used for marker-assisted
      selection (MAS) of seedling heat tolerance during dual-purpose wheat breeding.

PMID- 30233618
TI  - Endophytic Microbial Consortia of Phytohormones-Producing Fungus Paecilomyces
      formosus LHL10 and Bacteria Sphingomonas sp. LK11 to Glycine max L. Regulates
      Physio-hormonal Changes to Attenuate Aluminum and Zinc Stresses.
AB  - The compatible microbial consortia containing fungal and bacterial symbionts
      acting synergistically are applied to improve plant growth and eco-physiological
      responses in extreme crop growth conditions. However, the interactive effects of
      phytohormones-producing endophytic fungal and bacterial symbionts plant growth
      and stress tolerance under heavy metal stress have been least known. In the
      current study, the phytohormones-producing endophytic Paecilomyces formosus LHL10
      and Sphingomonas sp. LK11 revealed potent growth and tolerance during their
      initial screening against combined Al and Zn (2.5 mM each) stress. This was
      followed with their co-inoculation in the Al- and Zn-stressed Glycine max L.
      plants, showing significantly higher plant growth attributes (shoot/root length,
      fresh/dry weight, and chlorophyll content) than the plants solely inoculated with
      LHL10 or LK11 and the non-inoculated (control) plants under metal stresses.
      Interestingly, under metal stress, the consortia exhibited lower metal uptake and
      inhibited metal transport in roots. Metal-induced oxidative stresses were
      modulated in co-inoculated plants through reduced hydrogen peroxide, lipid
      peroxidation, and antioxidant enzymes (catalase and superoxide dismutase) in
      comparison to the non-inoculated plants. In addition, endophytic co-inoculation
      enhanced plant macronutrient uptake (P, K, S, and N) and modulated soil enzymatic
      activities under stress conditions. It significantly downregulated the expression
      of heavy metal ATPase genes GmHMA13, GmHMA18, GmHMA19, and GmPHA1 and upregulated
      the expression of an ariadne-like ubiquitin ligase gene GmARI1 under heavy metals
      stress. Furthermore, the endogenous phytohormonal contents of co-inoculated
      plants revealed significantly enhanced gibberellins and reduced abscisic acid and
      jasmonic acid contents, suggesting that this endophytic interaction mitigated the
      adverse effect of metal stresses in host plants. In conclusion, the co
      inoculation of the endophytic fungus LHL10 and bacteria LK11 actively contributed
      to the tripartite mutualistic symbiosis in G. max under heavy metal stresses;
      this could be used an excellent strategy for sustainable agriculture in the heavy
      metal-contaminated fields.

PMID- 30233619
TI  - Identification of a Spotted Leaf Sheath Gene Involved in Early Senescence and
      Defense Response in Rice.
AB  - Lesion mimic mutants (LMMs) commonly exhibit spontaneous cell death similar to
      the hypersensitive defense response that occurs in plants in response to pathogen
      infection. Several lesion mimic mutants have been isolated and characterized, but
      their molecular mechanisms remain largely unknown. Here, a spotted leaf sheath
      (sles) mutant derived from japonica cultivar Koshihikari is described. The sles
      phenotype differed from that of other LMMs in that lesion mimic spots were
      observed on the leaf sheath rather than on leaves. The sles mutant displayed
      early senescence, as shown, by color loss in the mesophyll cells, a decrease in
      chlorophyll content, and upregulation of chlorophyll degradation-related and
      senescence-associated genes. ROS content was also elevated, corresponding to
      increased expression of genes encoding ROS-generating enzymes. Pathogenesis
      related genes were also activated and showed improved resistance to pathogen
      infection on the leaf sheath. Genetic analysis revealed that the mutant phenotype
      was controlled by a single recessive nuclear gene. Genetic mapping and sequence
      analysis showed that a single nucleotide substitution in the sixth exon of
      LOC_Os07g25680 was responsible for the sles mutant phenotype and this was
      confirmed by T-DNA insertion line. Taken together, our results revealed that SLES
      was associated with the formation of lesion mimic spots on the leaf sheath
      resulting early senescence and defense responses. Further examination of SLES
      will facilitate a better understanding of the molecular mechanisms involved in
      ROS homeostasis and may also provide opportunities to improve pathogen resistance
      in rice.

PMID- 30233621
TI  - Whole Mount in situ Localization of miRNAs and mRNAs During Somatic Embryogenesis
      in Arabidopsis.
AB  - Somatic embryogenesis (SE) results from the transition of differentiated plant
      somatic cells into embryogenic cells that requires the extensive reprogramming of
      the somatic cell transcriptome. Commonly, the SE-involved genes are identified by
      analyzing the heterogeneous population of explant cells and thus, it is necessary
      to validate the expression of the candidate genes in the cells that are competent
      for embryogenic transition. Here, we optimized and implemented the whole mount in
      situ hybridization (WISH) method (Bleckmann and Dresselhaus, 2016; Dastidar et
      al., 2016) in order to analyze the spatiotemporal localization of miRNAs (miR156,
      miR166, miR390, miR167) and mRNAs such as WOX5 and PHABULOSA-target of miR165/166
      during the SE that is induced in Arabidopsis explants. This study presents a
      detailed step-by-step description of the WISH procedure in which DIG-labeled LNA
      and RNA probes were used to detect miRNAs and mRNAs, respectively. The usefulness
      of the WISH in the functional analysis of the SE-involved regulatory pathways is
      demonstrated and the advantages of this method are highlighted: (i) the ability
      to analyze intact non-sectioned plant tissue; (ii) the specificity of transcript
      detection; (iii) the detection of miRNA; and (iv) a semi-quantitative assessment
      of the RNA abundance.

PMID- 30233620
TI  - Genome-Wide Association Studies Reveal Genetic Variation and Candidate Genes of
      Drought Stress Related Traits in Cotton (Gossypium hirsutum L.).
AB  - Cotton is an important industrial crop worldwide and upland cotton (Gossypium
      hirsutum L.) is most widely cultivated in the world. Due to ever-increasing water
      deficit, drought stress brings a major threat to cotton production. Thus, it is
      important to reveal the genetic basis under drought stress and develop drought
      tolerant cotton cultivars. To address this issue, in present study, 319 upland
      cotton accessions were genotyped by 55,060 single nucleotide polymorphisms (SNPs)
      from high-density CottonSNP80K array and phenotyped nine drought tolerance
      related traits. The two datasets were used to identify quantitative trait
      nucleotides (QTNs) for the above nine traits using multi-locus random-SNP-effect
      mixed linear model method. As a result, a total of 20 QTNs distributed on 16
      chromosomes were found to be significantly associated with six drought tolerance
      related traits. Of the 1,326 genes around the 20 QTNs, 205 were induced after
      drought stress treatment, and 46 were further mapped to Gene ontology (GO) term
      "response to stress." Taken genome-wide association study (GWAS) analysis, RNA
      seq data and qRT-PCR verification, four genes, RD2 encoding a response to
      desiccation 2 protein, HAT22 encoding a homeobox-leucine zipper protein, PIP2
      encoding a plasma membrane intrinsic protein 2, and PP2C encoding a protein
      phosphatase 2C, were proposed to be potentially important for drought tolerance
      in cotton. These results will deepen our understanding of the genetic basis of
      drought stress tolerance in cotton and provide candidate markers to accelerate
      the development of drought-tolerant cotton cultivars.

PMID- 30233622
TI  - Plant Silicon and Phytolith Research and the Earth-Life Superdiscipline.

PMID- 30233623
TI  - Involvement of Calcium and Calmodulin in Nitric Oxide-Regulated Senescence of Cut
      Lily Flowers.
AB  - Both nitric oxide (NO) and calcium ion (Ca2+)/calmodulin (CaM) have been shown to
      regulate the senescence of cut flowers. However, not much is known about the
      crosstalk between NO and Ca2+/CaM during the senescence of cut flowers. In this
      study, cut Oriental * Trumpet hybrid lily "Manissa" were used to investigate the
      roles and relationship between NO and Ca2+/CaM during postharvest freshness. The
      results show that the effects of CaCl2 or NO donor SNAP on the vase life, maximum
      flower diameter and hours until full opening were dose-dependent, with an optimum
      concentration of 20 mM CaCl2 or 100 MUM SNAP. However, Ca2+ chelators EGTA or
      BAPTA/AM, Ca2+ channel inhibitors LaCl3 or nifedipine and CaM antagonists W-7 or
      TFP inhibited the promotion of SNAP. SNAP applied alone significantly increased
      the endogenous Ca2+/CaM contents in cut lily flowers, while EGTA, BAPTA/AM,
      LaCl3, nifedipine, W-7, and TFP decreased the advancement of SNAP. In addition,
      the SNAP-induced Ca2+-ATPase activity was more than twice as much as the control,
      but EGTA, BAPTA/AM, LaCl3, nifedipine, W-7, and TFP also reversed the
      enhancement. Moreover, EGTA, BAPTA/AM, LaCl3, nifedipine, W-7, and TFP prevented
      the SNAP-induced upregulation of gene expression of CaM, CBL1, and CBL3, which is
      associated with calcium signaling pathway. Overall, these results suggest that
      Ca2+/CaM may function as downstream molecules in NO-regulated senescence of cut
      flowers.

PMID- 30233624
TI  - Allelic Variation and Distribution of the Major Maturity Genes in Different
      Soybean Collections.
AB  - Soybean time of flowering and maturity are genetically controlled by E genes.
      Different allelic combinations of these genes determine soybean adaptation to a
      specific latitude. The paper describes the first attempt to assess adaptation of
      soybean genotypes developed and realized at Institute of Field and Vegetable
      Crops, Novi Sad, Serbia [Novi Sad (NS) varieties and breeding lines] based on E
      gene variation, as well as to comparatively assess E gene variation in North
      American (NA), Chinese, and European genotypes, as most of the studies published
      so far deal with North-American and Chinese cultivars and breeding material.
      Allelic variation and distribution of the major maturity genes (E1, E2, E3, and
      E4) has been determined in 445 genotypes from soybean collections of NA ancestral
      lines, Chinese germplasm, and European varieties, as well as NS varieties and
      breeding lines. The study showed that allelic combinations of E1-E4 genes
      significantly determined the adaptation of varieties to different geographical
      regions, although they have different impacts on maturity. In general, each
      collection had one major E genotype haplogroup, comprising over 50% of the lines.
      The exceptions were European varieties that had two predominant haplogroups and
      NA ancestral lines distributed almost evenly among several haplogroups. As e1
      as/e2/E3/E4 was the most common genotype in NS population, present in the best
      performing genotypes in terms of yield, this specific allele combination was
      proposed as the optimal combination for the environments of Central-Eastern
      Europe.

PMID- 30233625
TI  - Signaling Molecule Hydrogen Sulfide Improves Seed Germination and Seedling Growth
      of Maize (Zea mays L.) Under High Temperature by Inducing Antioxidant System and
      Osmolyte Biosynthesis.
AB  - Hydrogen sulfide (H2S) is a novel type signaling molecule in plants. Seed
      germination is a key stage of life cycle of plants, which is vulnerable to
      environmental stress including high temperature. However, under high temperature
      stress, whether pre-soaking of maize seeds with NaHS (a H2S donor) could improve
      seed germination and seedling growth and the possible mechanisms are not
      completely clear. In this study, maize seeds pre-soaked with NaHS enhanced
      germination percentage, sprout length, root length, and fresh weight compared
      with the control without NaHS treatment, illustrating that H2S could improve
      maize seed germination and seedling growth under high temperature. In addition,
      in comparison to the control, NaHS pre-soaking stimulated antioxidant enzymes
      [ascorbate peroxidase (APX), glutathione reductase (GR), guaiacol peroxidase
      (GPX), superoxide dismutase (SOD), and catalase (CAT)] activities and the
      contents of water soluble non-enzymatic antioxidants [ascorbic acid (AsA) and
      glutathione (GSH)], as well as the ratio of reduced antioxidant to oxidized
      antioxidant. Moreover, pre-soaking with NaHS activated Delta1-pyrroline-5
      carboxylate synthetase (P5CS) and ornithine aminotransferase [OAT; both are rate
      limiting enzymes in proline (Pro) synthesis], betaine aldehyde dehydrogenase
      [BADH; a key enzyme in glycine betaine (GB)], and trehalose (Tre)-6-phosphate
      phosphatase (a key step in Tre synthesis), which in turn accumulated Pro, GB, and
      Tre in germinating seeds compared with the control. Also, an improved germination
      by NaHS under high temperature was reinforced by the above osmotic adjustment
      substances (osmolytes) alone, while deteriorated by the inhibitors of osmolyte
      biosynthesis [gabaculine (GAB), disulfiram (DSF), and sodium citrate (SC)]. These
      results imply that H2S could improve maize seed germination and seedling growth
      under high temperature by inducing antioxidant system and osmolyte biosynthesis.

PMID- 30233627
TI  - Regulatory Uncertainty Around New Breeding Techniques.
AB  - Emerging precision breeding techniques have great potential to develop new crop
      varieties with specific traits that can contribute to ensuring future food
      security in a time of increasing climate change pressures, such as disease,
      insects and drought. These techniques offer options for crop trait development in
      both private and public sector breeding programs. Yet, the success of new
      breeding techniques is not guaranteed at the scientific level alone: political
      influences and social acceptance significantly contribute to how crops will
      perform in the market. Using survey data, we report results from an international
      panel of experts regarding the institutional and social barriers that might
      impede the development of new plant technologies. Survey results clearly indicate
      that regulatory issues, social, and environmental concerns are critical to the
      success of precision breeding. The cross-regional analysis shows heterogeneity
      between Europeans and North Americans, particularly regarding political attitudes
      and social perceptions of targeted breeding techniques.

PMID- 30233626
TI  - The Importance of Marine Predators in the Provisioning of Ecosystem Services by
      Coastal Plant Communities.
AB  - Food web theory predicts that current global declines in marine predators could
      generate unwanted consequences for many marine ecosystems. In coastal plant
      communities (kelp, seagrass, mangroves, and salt marsh), several studies have
      documented the far-reaching effects of changing predator populations. Across
      coastal ecosystems, the loss of marine predators appears to negatively affect
      coastal plant communities and the ecosystem services they provide. Here, we
      discuss some of the documented and suspected effects of predators on coastal
      protection, carbon sequestration, and the stability and resilience of coastal
      plant communities. In addition, we present a meta-analysis to assess the strength
      and direction of trophic cascades in kelp forests, seagrasses, salt marshes, and
      mangroves. We demonstrate that the strength and direction of trophic cascades
      varied across ecosystem types, with predators having a large positive effect on
      plants in salt marshes, a moderate positive effect on plants in kelp and
      mangroves, and no effect on plants in seagrasses. Our analysis also identified
      that there is a paucity of literature on trophic cascades for all four coastal
      plant systems, but especially seagrass and mangroves. Our results demonstrate the
      crucial role of predators in maintaining coastal ecosystem services, but also
      highlights the need for further research before large-scale generalizations about
      the prevalence, direction, and strength of trophic cascade in coastal plant
      communities can be made.

PMID- 30233628
TI  - Metabolome and Lipidome Profiles of Populus * canescens Twig Tissues During
      Annual Growth Show Phospholipid-Linked Storage and Mobilization of C, N, and S.
AB  - The temperate climax tree species Fagus sylvatica and the floodplain tree species
      Populus * canescens possess contrasting phosphorus (P) nutrition strategies.
      While F. sylvatica has been documented to display P storage and mobilization
      (Netzer et al., 2017), this was not observed for Populus * canescens (Netzer et
      al., 2018b). Nevertheless, changes in the abundance of organic bound P in gray
      poplar trees indicated adaptation of the P nutrition to different needs during
      annual growth. The present study aimed at characterizing seasonal changes in
      metabolite and lipid abundances in gray poplar and uncovering differences in
      metabolite requirement due to specific needs depending on the season. Seasonal
      variations in the abundance of (i) sugar-Ps and phospholipids, (ii) amino acids,
      (iii) sulfur compounds, and (iv) carbon metabolites were expected. It was
      hypothesized that seasonal changes in metabolite levels relate to N, S, and C
      storage and mobilization. Changes in organic metabolites binding Pi (Porg) are
      supposed to support these processes. Variation in triacylglycerols, in sugar
      phosphates, in metabolites of the TCA cycle and in the amino acid abundance of
      poplar twig buds, leaves, bark, and wood were found to be linked to changes in
      metabolite abundances as well as to C, N, and S storage and mobilization
      processes. The observed changes support the view of a lack of any P storage in
      poplar. Yet, during dormancy, contents of phospholipids in twig bark and wood
      were highest probably due to frost-hardening and to its function in extra
      plastidic membranes such as amyloplasts, oleosomes, and protein bodies.
      Consistent with this assumption, in spring sugar-Ps increased when phospholipids
      declined and poplar plants entering the vegetative growth period and, hence,
      metabolic activity increases. These results indicate that poplar trees adopt a
      policy of P nutrition without P storage and mobilization that is different from
      their N- and S-nutrition strategies.

PMID- 30233629
TI  - Molecular Evolution of GDP-D-Mannose Epimerase (GME), a Key Gene in Plant
      Ascorbic Acid Biosynthesis.
AB  - The widespread ascorbic acid (AsA) plays a vital role in plant development and
      abiotic stress tolerance, but AsA concentration varies greatly among different
      plants. GDP-D-mannose epimerase (GME), which catalyzes GDP-D-mannose to GDP-L
      galactose or GDP-L-gulose, is a key enzyme in plant AsA biosynthesis pathway.
      Functions and expression patterns of GME have been well studied in previous
      works, however, little information is known about the evolutionary patterns of
      the gene. In this study, GME gene structure, corresponding conserved protein
      motifs and evolutionary relationships were systematically analyzed. A total of
      111 GME gene sequences were retrieved from 59 plant genomes, which representing
      almost all the major lineages of Viridiplantae: dicotyledons, monocotyledons,
      gymnosperms, pteridophytes, bryophytes, and chlorophytes. Results showed that
      homologs of GME were widely present in Viridiplantae. GME gene structures were
      conservative in higher plants, while varied greatly in the basal subgroups of the
      phylogeny including lycophytes, bryophytes, and chlorophytes, suggesting GME gene
      structure might have undergone severe differentiation at lower plant and then
      gradually fixed as plant evolution. The basic motifs of GME were strongly
      conserved throughout Viridiplantae, suggesting the conserved function of the
      protein. Molecular evolution analysis showed that strong purifying selection was
      the predominant force in the evolution of GME. A few branches and sites under
      episodic diversifying selection were identified and most of the branches located
      in the subgroup of chlorphytes, indicating episodic diversifying selection at a
      few branches and sites may play a role in the evolution of GME and diversifying
      selection may have occurred at the early stage of Viridiplantae. Our results
      provide novel insights into functional conservation and the evolution of GME.

PMID- 30233630
TI  - The Tryptophan decarboxylase 1 Gene From Aegilops variabilis No.1 Regulate the
      Resistance Against Cereal Cyst Nematode by Altering the Downstream Secondary
      Metabolite Contents Rather Than Auxin Synthesis.
AB  - Cereal cyst nematode (CCN, Heterodera avenae) is a most important pathogen of
      wheat and causes tremendous yield loss annually over the world. Since the lack of
      resistance materials among wheat cultivars, identification and characterization
      of the resistance-related genes from the relatives of wheat is a necessary and
      efficient way. As a close relative of wheat with high resistance against CCN,
      Aegilops variabilis No.1 is believed to be a valuable source for wheat breeding
      against this devastating disease. However so far, very few resistance-associated
      genes have been characterized from this species. In this study, we present that
      the tryptophan decarboxylase genes from Ae. variabilis No.1 (AeVTDC1 and AeVTDC2)
      were both induced by CCN juveniles at the early stage of resistance response (30
      h post-inoculation), with AeVTDC1 more sensitive to CCN infection than AeVTDC2.
      Silencing of AeVTDC1 led to compromised immunity to CCN with more CCN intrusion
      into roots; while overexpression AeVTDC1 in Nicotiana tabacum dramatically
      enhanced the resistance of plants by reducing the knots formed on roots.
      Metabolism analysis showed that the contents of secondary metabolites with
      activity of resistance to varied pathogens correlated with the expression level
      of AeVTDC1 in both Ae. variabilis No.1 and the transgenic tobacco plants. In
      addition, the content of IAA was not affected by either silencing or
      overexpressing of AeVTDC1. Hence, our research provided AeVTDC1 a valuable target
      that mediates resistance to CCN and root knot nematode (RKN, Meloidogyne naasi)
      without influencing the auxin biosynthesis.

PMID- 30233631
TI  - The Pepper Late Embryogenesis Abundant Protein, CaDIL1, Positively Regulates
      Drought Tolerance and ABA Signaling.
AB  - Plants as sessile organisms constantly respond to environmental stress during
      their growth and development. The regulation of transpiration via stomata plays
      crucial roles in plant adaptation to drought stress. Many enzyme-encoding genes
      are involved in regulation of transpiration via modulating stomatal opening and
      closure. Here, we demonstrate that Capsicum annuum Drought Induced Late
      embryogenesis abundant protein 1 (CaDIL1) gene is a critical regulator of
      transpirational water loss in pepper. The expression of CaDIL1 in pepper leaves
      was upregulated after exposure to abscisic acid (ABA) and drought. Phenotype
      analysis showed that CaDIL1-silenced pepper and CaDIL1-overexpressing (OX)
      Arabidopsis transgenic plants exhibited reduced and enhanced drought tolerance,
      respectively, accompanied by an altered water loss. Furthermore, ABA sensitivity
      was significantly lower in CaDIL1-silenced pepper, but higher in CaDIL1-OX
      plants, than that in control plants, which resulted in opposite responses to
      drought stress in these two plant types. Collectively, our data suggest that
      CaDIL1 positively regulates the ABA signaling and drought stress tolerance.

PMID- 30233633
TI  - SiYGL2 Is Involved in the Regulation of Leaf Senescence and Photosystem II
      Efficiency in Setaria italica (L.) P. Beauv.
AB  - A yellow-green leaf mutant was isolated from EMS-mutagenized lines of Setaria
      italica variety Yugu1. Map-based cloning revealed the mutant gene is a homolog of
      Arabidopsis thaliana AtEGY1. EGY1 (ethylene-dependent gravitropism-deficient and
      yellow-green 1) is an ATP-independent metalloprotease (MP) that is required for
      chloroplast development, photosystem protein accumulation, hypocotyl
      gravitropism, leaf senescence, and ABA signal response in A. thaliana. However,
      the function of EGY1 in monocotyledonous C4 plants has not yet been described.
      The siygl2 mutant is phenotypically characterized by chlorotic organs, premature
      senescence, and damaged PS II function. Sequence comparisons of the AtEGY1 and
      SiYGL2 proteins reveals the potential for SiYGL2 to encode a partially functional
      protein. Phenotypic characterization and gene expression analysis suggested that
      SiYGL2 participates in the regulation of chlorophyll content, leaf senescence
      progression, and PS II function. Additionally, our research will contribute to
      further characterization of the mechanisms regulating leaf senescence and
      photosynthesis in S. italica, and in C4 plants in general.

PMID- 30233632
TI  - Characterization of Arabidopsis thaliana Hydroxyphenylpyruvate Reductases in the
      Tyrosine Conversion Pathway.
AB  - Tyrosine serves as a precursor to several types of plant natural products of
      medicinal or nutritional interests. Hydroxyphenylpyruvate reductase (HPPR), which
      catalyzes the reduction of 4-hydroxyphenylpyruvic acid (pHPP) to 4
      hydroxyphenyllactic acid (pHPL), has been shown to be the key enzyme in the
      biosynthesis of rosmarinic acid (RA) from tyrosine and, so far, HPPR activity has
      been reported only from the RA-accumulating plants. Here, we show that HPPR
      homologs are widely distributed in land plants. In Arabidopsis thaliana, which
      does not accumulate RA at detectable level, two homologs (HPPR2 and HPPR3) are
      functional in reducing pHPP. Phylogenetic analysis placed HPPR2 and HPPR3 in two
      separate groups within the HPPR clade, and HPPR2 and HPPR3 are distinct from
      HPR1, a peroxisomal hydroxypyruvate reductase (HPR). In vitro characterization of
      the recombinant proteins revealed that HPPR2 has both HPR and HPPR activities,
      whereas HPPR3 has a strong preference for pHPP, and both enzymes are localized in
      the cytosol. Arabidopsis mutants defective in either HPPR2 or HPPR3 contained
      lower amounts of pHPL and were impaired in conversion of tyrosine to pHPL.
      Furthermore, a loss-of-function mutation in tyrosine aminotransferase (TAT) also
      reduced the pHPL accumulation in plants. Our data demonstrate that in Arabidopsis
      HPPR2 and HPPR3, together with TAT1, constitute to a probably conserved
      biosynthetic pathway from tyrosine to pHPL, from which some specialized
      metabolites, such as RA, can be generated in specific groups of plants. Our
      finding may have broad implications for the origins of tyrosine-derived
      specialized metabolites in general.

PMID- 30233634
TI  - Genome-Wide Association Mapping of Starch Pasting Properties in Maize Using
      Single-Locus and Multi-Locus Models.
AB  - Maize starch plays a critical role in food processing and industrial application.
      The pasting properties, the most important starch characteristics, have enormous
      influence on fabrication property, flavor characteristics, storage, cooking, and
      baking. Understanding the genetic basis of starch pasting properties will be
      beneficial for manipulation of starch properties for a given purpose. Genome-wide
      association studies (GWAS) are becoming a powerful tool for dissecting the
      complex traits. Here, we carried out GWAS for seven pasting properties of maize
      starch with a panel of 230 inbred lines and 145,232 SNPs using one single-locus
      method, genome-wide efficient mixed model association (GEMMA), and three multi
      locus methods, FASTmrEMMA, FarmCPU, and LASSO. We totally identified 60
      quantitative trait nucleotides (QTNs) for starch pasting properties with these
      four GWAS methods. FASTmrEMMA detected the most QTNs (29), followed by FarmCPU
      (19) and LASSO (12), GEMMA detected the least QTNs (7). Of these QTNs, seven QTNs
      were identified by more than one method simultaneously. We further investigated
      locations of these significantly associated QTNs for possible candidate genes.
      These candidate genes and significant QTNs provide the guidance for further
      understanding of molecular mechanisms of starch pasting properties. We also
      compared the statistical powers and Type I errors of the four GWAS methods using
      Monte Carlo simulations. The results suggest that the multi-locus method is more
      powerful than the single-locus method and a combination of these multi-locus
      methods could help improve the detection power of GWAS.

PMID- 30233635
TI  - Gas Exchange Rates Decrease and Leaf Temperature Increases in Nicotiana
      benthamiana Leaves Transiently Overexpressing Hemagglutinin in an Agrobacterium
      Assisted Viral Vector System.
AB  - In this study, gas exchange characteristics and temperature of Nicotiana
      benthamiana leaves transiently overexpressing hemagglutinin (HA), an influenza
      vaccine antigen, with an Agrobacterium tumefaciens-assisted viral vector were
      investigated. Inoculation of leaves with an empty viral vector not containing the
      HA gene decreased the net photosynthetic rate (Pn) and transpiration rate (T)
      from 2 to 3 days post-infiltration (DPI) in the A. tumefaciens suspension.
      Expression of HA with the vector decreased Pn and T to much lower levels until 4
      DPI. Such significant decreases were not observed in leaves infiltrated with
      suspension of A. tumefaciens not carrying the viral vector or in uninfiltrated
      leaves. Thus, viral vector inoculation itself decreased Pn and T to a certain
      extent and the HA expression further decreased them. The decreases in Pn and T in
      empty vector-inoculated and HA expression vector-inoculated leaves were
      associated with decreases in stomatal conductance, suggesting that the reduction
      of gas exchange rates was caused at least in part by stomatal closure. More
      detailed gas exchange and chlorophyll fluorescence analyses revealed that in HA
      vector-inoculated leaves, the capacity of ribulose-1,5-bisphosphate
      carboxylase/oxygenase to assimilate CO2 and the capacity of photosynthetic
      electron transport in planta were downregulated, which contributed also to the
      decrease in Pn. Leaf temperature (LT) increased in viral vector-inoculated
      leaves, which was associated with the decrease in T. When HA vector-inoculated
      leaves were grown at air temperatures (ATs) of 21, 23, and 26 degrees C post
      infiltration, HA accumulated earlier in leaves and the days required for HA
      content to attain its peak became shorter, as AT was higher. The highest LT was
      found 1-2 days earlier than the highest leaf HA content under all post
      infiltration AT conditions. This phenomenon could be applicable in a non
      destructive technique to detect the optimum harvesting date for individual plants
      to determine the day when leaf HA content reaches its maximum level, irrespective
      of spatiotemporal variation of AT, in a plant growth facility.

PMID- 30233636
TI  - Metabolic Profiling and Post-harvest Behavior of "Dottato" Fig (Ficus carica L.)
      Fruit Covered With an Edible Coating From O. ficus-indica.
AB  - Fig fruits are usually highly sensitive to some physiopathological disorders
      during post-harvest life, such as softening and skin cracking. Indeed, the use of
      edible coating (EC) has been evaluated in several fruit crops to reduce fruit
      post-harvest transpiration and to maintain fruit visual quality. The aim of this
      study was to determine the post-harvest metabolic response of breba figs treated
      with mucilage extract from O puntia ficus-indica cladodes, using an untargeted
      metabolomic approach. Coated and non-coated (control) fruit were sealed in
      plastic bags, and stored at 4 degrees C for 7 days. The effect of the ECs on
      their quality fruit during cold storage and qualitative attributes were evaluated
      by analyzing the fruit primary metabolism and other qualitative parameters such
      as total soluble solids (TSS) content, titratable acidity (TA), fresh weight loss
      and firmness. Results underlined that EC was effective in maintaining fruit fresh
      weight, and fruit firmness. Stepwise discriminant analysis was able to
      discriminate fruit conditions. Alanine, xylulose, aspartic acid, glutamic, acid
      and 2,5-dihydroxypyrazine showed a significant role on discriminating edible
      coated fruit from untreated ones. Principal component analysis (PCA) was able to
      highlight clear differences in the overall metabolism changes between untreated
      and treated fruit. The application of EC significantly mitigated the decrease of
      most of the aminoacid content during cold storage. EC treatment caused the
      changes of several organic acids in comparison to untreated control, increasing
      the amount of carbohydrates and other key metabolites, such as beta-sitosterol,
      glycerol, and uracil. These results clearly showed the drastic effects of EC on
      fig metabolism during post-harvest and shed light on the beneficial mechanisms of
      this treatment.

PMID- 30233637
TI  - Bioinformatics Analysis Identifies p53 as a Candidate Prognostic Biomarker for
      Neuropathic Pain.
AB  - Neuropathic pain (NP) is a type of chronic pain that is different from the common
      type of pain. The mechanisms of NP are still poorly understood. Exploring the key
      genes and neurobiological changes in NP could provide important diagnostic and
      treatment tools for clinicians. GSE24982 is an mRNA-seq dataset that we
      downloaded from the Gene Expression Omnibus database to identify key genes in NP.
      Differentially expressed genes (DEGs) were identified using the BRB-ArrayTools
      software and R. Functional and pathway enrichment analyses of the DEGs were
      performed using Metascape. A protein-protein interaction network was created and
      visualized using Cytoscape. A total of 123 upregulated DEGs were obtained. Among
      these genes, p53 was the node with the highest degree; hence, we validated it
      experimentally using a chronic constriction injury mouse model. Our results
      showed that overexpression of the p53 gene, and the subsequent increase in
      caspase-3 expression, in dorsal root ganglion neurons led to increased apoptotic
      changes in these neurons. p53 may therefore be partly responsible for the
      development of chronic constriction injury-induced NP.

PMID- 30233638
TI  - Integrative Analyses of Transcriptome Sequencing Identify Functional miRNAs in
      the Chicken Embryo Fibroblasts Cells Infected With Reticuloendotheliosis Virus.
AB  - In this study, we found a much higher proportion of reticuloendotheliosis virus
      (REV) infected chicken embryo fibroblasts (CEF) were in active cell division
      phase than that of control cells which indicated that REV can affect the fate of
      CEF. So, we performed high-throughput sequencing and transcriptomic analysis to
      identify functional miRNAs, in order to figure out the possible mechanism in the
      interaction of REV with CEF. In total, 50 differentially expressed miRNAs
      (DEmiRNAs) were identified. Then target genes of DEmiRNAs were predicted and
      identified by transcriptome profile results. Kyoto Encyclopedia of Genes and
      Genomes (KEGG) enrichment were conducted to analyze the identified target genes
      of miRNAs which showed that metabolism, cell cycle, and apoptosis were the most
      related pathways involved in infection of REV. We analyzed the genes related to
      cell cycle which indicated that CyclinD1-CDK6 complex played an important role in
      regulating the transition of the cell cycle from G1 phase to S phase during REV
      infection. Fluorescence microscope identification showed that REV inhibited the
      apoptosis of CEF which was in accordance with transcriptome results. A novel
      miRNA, named novel-72 was found, KEGG analysis was conducted to predict the
      biological function of its target genes which showed that those target genes were
      significantly enriched in mTOR signaling pathway and functioned to promote cell
      cycle and cell growth during the REV infection. In conclusion, REV could induce
      the up-regulation of cell metabolism, cell cycle and mTOR signaling pathway while
      inhibit apoptosis of the cell.

PMID- 30233639
TI  - Bivariate Causal Discovery and Its Applications to Gene Expression and Imaging
      Data Analysis.
AB  - The mainstream of research in genetics, epigenetics, and imaging data analysis
      focuses on statistical association or exploring statistical dependence between
      variables. Despite their significant progresses in genetic research,
      understanding the etiology and mechanism of complex phenotypes remains elusive.
      Using association analysis as a major analytical platform for the complex data
      analysis is a key issue that hampers the theoretic development of genomic science
      and its application in practice. Causal inference is an essential component for
      the discovery of mechanical relationships among complex phenotypes. Many
      researchers suggest making the transition from association to causation. Despite
      its fundamental role in science, engineering, and biomedicine, the traditional
      methods for causal inference require at least three variables. However,
      quantitative genetic analysis such as QTL, eQTL, mQTL, and genomic-imaging data
      analysis requires exploring the causal relationships between two variables. This
      paper will focus on bivariate causal discovery with continuous variables. We will
      introduce independence of cause and mechanism (ICM) as a basic principle for
      causal inference, algorithmic information theory and additive noise model (ANM)
      as major tools for bivariate causal discovery. Large-scale simulations will be
      performed to evaluate the feasibility of the ANM for bivariate causal discovery.
      To further evaluate their performance for causal inference, the ANM will be
      applied to the construction of gene regulatory networks. Also, the ANM will be
      applied to trait-imaging data analysis to illustrate three scenarios: presence of
      both causation and association, presence of association while absence of
      causation, and presence of causation, while lack of association between two
      variables. Telling cause from effect between two continuous variables from
      observational data is one of the fundamental and challenging problems in omics
      and imaging data analysis. Our preliminary simulations and real data analysis
      will show that the ANMs will be one of choice for bivariate causal discovery in
      genomic and imaging data analysis.

PMID- 30233641
TI  - Sensory Difficulties in Children With an FMR1 Premutation.
AB  - Abnormal sensory processing is one of the core characteristics of the fragile X
      phenotype. Studies of young children with fragile X syndrome (FXS) and the FMR1
      premutation have shown sensory challenges as early as infancy and into early
      childhood. This study sought to examine differences in sensory difficulties in
      children with an FMR1 premutation compared with children with FXS and typically
      developing children. We conducted an online survey of 176 parents of affected
      children (FXS or FMR1 premutation). Most respondents were mothers who are
      Caucasian (86%), have a 4-year college or graduate degree (68%), and are married
      (92%). Children ranged in age from 5 to 18, with a mean age of 13.0 years (3.3
      SD). Participants completed the BBC Sensory Scales, a 50-item Likert-type scale
      (1 = Almost Always, 4 = Almost Never) comprised of 8 subscales that assessed
      auditory processing, visual processing, tactile processing, and eating and
      feeding behaviors. Mean scores were calculated for the items and each of the
      subscales. Non-parametric tests examined differences in child and family-level
      variables. Across all BBCSS subscales, children with an FMR1 premutation
      displayed more sensory challenges than typically developing children. For six out
      of the eight subscales, children with the full mutation had the lowest scores
      indicating more sensory challenges, but this was closely followed by children
      with an FMR1 premutation. Fragile X status was associated with seven of the eight
      subscales; children with an FMR1 premutation did not differ from children with
      FXS on any of the subscales but had more digestive problems than children with no
      fragile X. Gender, autism status, and family income were also related to sensory
      sensitivities. In conclusion, these data provide further evidence that some
      children with an FMR1 premutation experience sensory difficulties that are
      similar to children with FXS but different than typically developing children.

PMID- 30233642
TI  - Early Onset Multiple Primary Tumors in Atypical Presentation of Cowden Syndrome
      Identified by Whole-Exome-Sequencing.
AB  - A family with an aggregation of rare early onset multiple primary tumors has been
      managed in our oncogenetics department: the proband developed four early onset
      carcinomas between ages 31 and 33 years, including acral melanoma, bilateral
      clear cell renal carcinoma (RC), and follicular variant of papillary thyroid
      carcinoma. The proband's parent developed orbital lymphoma and small intestine
      mucosa-associated lymphoid tissue (MALT) lymphoma between 40 and 50 years old.
      Whole-exome-sequencing (WES) of the nuclear family (proband, parents, and
      sibling) identified in the proband a de novo deleterious heterozygous mutation
      c.1003C > T (p.Arg335*) in the phosphatase and tensin homolog (PTEN) gene.
      Furthermore, WES allowed analysis of the nuclear family's genetic background, and
      identified deleterious variants in two candidate modifier genes: CEACAM1 and
      MIB2. CEACAM1, a tumor suppressor gene, presents loss of expression in clear cell
      RC and is involved in proliferation of B cells. It could explain in part the
      phenotype of proband's parent and the occurrence of clear cell RC in the proband.
      Deleterious mutations in the MIB2 gene are associated with melanoma invasion, and
      could explain the occurrence of melanoma in the proband. Cowden syndrome is a
      hereditary autosomal dominant disorder associated with increased risk of muco
      cutaneous features, hamartomatous tumors, and cancer. This atypical presentation,
      including absence of muco-cutaneous lesions, four primary early onset tumors and
      bilateral clear cell RC, has not been described before. This encourages including
      the PTEN gene in panel testing in the context of early onset RC, whatever the
      histological subtype. Further studies are required to determine the implication
      of CEACAM1 and MIB2 in the severity of Cowden syndrome in our proband and
      occurrence of early onset MALT lymphoma in a parent.

PMID- 30233640
TI  - Rare Genetic Blood Disease Modeling in Zebrafish.
AB  - Hematopoiesis results in the correct formation of all the different blood cell
      types. In mammals, it starts from specific hematopoietic stem and precursor cells
      residing in the bone marrow. Mature blood cells are responsible for supplying
      oxygen to every cell of the organism and for the protection against pathogens.
      Therefore, inherited or de novo genetic mutations affecting blood cell formation
      or the regulation of their activity are responsible for numerous diseases
      including anemia, immunodeficiency, autoimmunity, hyper- or hypo-inflammation,
      and cancer. By definition, an animal disease model is an analogous version of a
      specific clinical condition developed by researchers to gain information about
      its pathophysiology. Among all the model species used in comparative medicine,
      mice continue to be the most common and accepted model for biomedical research.
      However, because of the complexity of human diseases and the intrinsic
      differences between humans and other species, the use of several models (possibly
      in distinct species) can often be more helpful and informative than the use of a
      single model. In recent decades, the zebrafish (Danio rerio) has become
      increasingly popular among researchers, because it represents an inexpensive
      alternative compared to mammalian models, such as mice. Numerous advantages make
      it an excellent animal model to be used in genetic studies and in particular in
      modeling human blood diseases. Comparing zebrafish hematopoiesis to mammals, it
      is highly conserved with few, significant differences. In addition, the zebrafish
      model has a high-quality, complete genomic sequence available that shows a high
      level of evolutionary conservation with the human genome, empowering genetic and
      genomic approaches. Moreover, the external fertilization, the high fecundity and
      the transparency of their embryos facilitate rapid, in vivo analysis of
      phenotypes. In addition, the ability to manipulate its genome using the last
      genome editing technologies, provides powerful tools for developing new disease
      models and understanding the pathophysiology of human disorders. This review
      provides an overview of the different approaches and techniques that can be used
      to model genetic diseases in zebrafish, discussing how this animal model has
      contributed to the understanding of genetic diseases, with a specific focus on
      the blood disorders.

PMID- 30233643
TI  - The Lysine Demethylase dKDM2 Is Non-essential for Viability, but Regulates
      Circadian Rhythms in Drosophila.
AB  - Post-translational modification of histones, such as histone methylation
      controlled by specific methyltransferases and demethylases, play critical roles
      in modulating chromatin dynamics and transcription in eukaryotes. Misregulation
      of histone methylation can lead to aberrant gene expression, thereby contributing
      to abnormal development and diseases such as cancer. As such, the mammalian
      lysine-specific demethylase 2 (KDM2) homologs, KDM2A and KDM2B, are either
      oncogenic or tumor suppressive depending on specific pathological contexts.
      However, the role of KDM2 proteins during development remains poorly understood.
      Unlike vertebrates, Drosophila has only one KDM2 homolog (dKDM2), but its
      functions in vivo remain elusive due to the complexities of the existing mutant
      alleles. To address this problem, we have generated two dKdm2 null alleles using
      the CRISPR/Cas9 technique. These dKdm2 homozygous mutants are fully viable and
      fertile, with no developmental defects observed under laboratory conditions.
      However, the dKdm2 null mutant adults display defects in circadian rhythms. Most
      of the dKdm2 mutants become arrhythmic under constant darkness, while the
      circadian period of the rhythmic mutant flies is approximately 1 h shorter than
      the control. Interestingly, lengthened circadian periods are observed when dKDM2
      is overexpressed in circadian pacemaker neurons. Taken together, these results
      demonstrate that dKdm2 is not essential for viability; instead, dKDM2 protein
      plays important roles in regulating circadian rhythms in Drosophila. Further
      analyses of the molecular mechanisms of dKDM2 and its orthologs in vertebrates
      regarding the regulation of circadian rhythms will advance our understanding of
      the epigenetic regulations of circadian clocks.

PMID- 30233644
TI  - Identification of Hyper-Methylated Tumor Suppressor Genes-Based Diagnostic Panel
      for Esophageal Squamous Cell Carcinoma (ESCC) in a Chinese Han Population.
AB  - DNA methylation-based biomarkers were suggested to be promising for early cancer
      diagnosis. However, DNA methylation-based biomarkers for esophageal squamous cell
      carcinoma (ESCC), especially in Chinese Han populations have not been identified
      and evaluated quantitatively. Candidate tumor suppressor genes (N = 65) were
      selected through literature searching and four public high-throughput DNA
      methylation microarray datasets including 136 samples totally were collected for
      initial confirmation. Targeted bisulfite sequencing was applied in an independent
      cohort of 94 pairs of ESCC and normal tissues from a Chinese Han population for
      eventual validation. We applied nine different classification algorithms for the
      prediction to evaluate to the prediction performance. ADHFE1, EOMES, SALL1 and
      TFPI2 were identified and validated in the ESCC samples from a Chinese Han
      population. All four candidate regions were validated to be significantly hyper
      methylated in ESCC samples through Wilcoxon rank-sum test (ADHFE1, P = 1.7 * 10
      3; EOMES, P = 2.9 * 10-9; SALL1, P = 3.9 * 10-7; TFPI2, p = 3.4 * 10-6). Logistic
      regression based prediction model shown a moderately ESCC classification
      performance (Sensitivity = 66%, Specificity = 87%, AUC = 0.81). Moreover,
      advanced classification method had better performances (random forest and naive
      Bayes). Interestingly, the diagnostic performance could be improved in non
      alcohol use subgroup (AUC = 0.84). In conclusion, our data demonstrate the
      methylation panel of ADHFE1, EOMES, SALL1 and TFPI2 could be an effective
      methylation-based diagnostic assay for ESCC.

PMID- 30233647
TI  - Computational Tools for Splicing Defect Prediction in Breast/Ovarian Cancer
      Genes: How Efficient Are They at Predicting RNA Alterations?
AB  - In silico tools for splicing defect prediction have a key role to assess the
      impact of variants of uncertain significance. Our aim was to evaluate the
      performance of a set of commonly used splicing in silico tools comparing the
      predictions against RNA in vitro results. This was done for natural splice sites
      of clinically relevant genes in hereditary breast/ovarian cancer (HBOC) and Lynch
      syndrome. A study divided into two stages was used to evaluate SSF-like,
      MaxEntScan, NNSplice, HSF, SPANR, and dbscSNV tools. A discovery dataset of 99
      variants with unequivocal results of RNA in vitro studies, located in the 10
      exonic and 20 intronic nucleotides adjacent to exon-intron boundaries of BRCA1,
      BRCA2, MLH1, MSH2, MSH6, PMS2, ATM, BRIP1, CDH1, PALB2, PTEN, RAD51D, STK11, and
      TP53, was collected from four Spanish cancer genetic laboratories. The best stand
      alone predictors or combinations were validated with a set of 346 variants in the
      same genes with clear splicing outcomes reported in the literature. Sensitivity,
      specificity, accuracy, negative predictive value (NPV) and Mathews Coefficient
      Correlation (MCC) scores were used to measure the performance. The discovery
      stage showed that HSF and SSF-like were the most accurate for variants at the
      donor and acceptor region, respectively. The further combination analysis
      revealed that HSF, HSF+SSF-like or HSF+SSF-like+MES achieved a high performance
      for predicting the disruption of donor sites, and SSF-like or a sequential
      combination of MES and SSF-like for predicting disruption of acceptor sites. The
      performance confirmation of these last results with the validation dataset,
      indicated that the highest sensitivity, accuracy, and NPV (99.44%, 99.44%, and
      96.88, respectively) were attained with HSF+SSF-like or HSF+SSF-like+MES for
      donor sites and SSF-like (92.63%, 92.65%, and 84.44, respectively) for acceptor
      sites. We provide recommendations for combining algorithms to conduct in silico
      splicing analysis that achieved a high performance. The high NPV obtained allows
      to select the variants in which the study by in vitro RNA analysis is mandatory
      against those with a negligible probability of being spliceogenic. Our study also
      shows that the performance of each specific predictor varies depending on whether
      the natural splicing sites are donors or acceptors.

PMID- 30233648
TI  - Williams-Beuren Syndrome as a Potential Risk Factor for Burkitt Lymphoma.
AB  - Williams-Beuren syndrome (WBS) is a multisystemic neurodevelopmental disorder
      caused by a hemizygous deletion on chromosome 7q11.23. Though at present there is
      a limited number of reports on WBS patients with tumors, most cases are related
      to blood cancer in children with WBS. We describe a case of Burkitt lymphoma in a
      21-year-old man with WBS. In addition to providing a summary of published reports
      describing tumors observed in patients with WBS, we present a hypothesis about a
      possible mechanism of oncogenesis. In particular, we identified some
      significantly dysregulated cancer-related genes using blood samples from this
      patient at the age of 19 years (who have not yet developed Burkitt lymphoma). Our
      findings may provide a new perspective on the relation between WBS and Burkitt
      lymphoma.

PMID- 30233645
TI  - Genome Editing of Pigs for Agriculture and Biomedicine.
AB  - Pigs serve as an important agricultural resource and animal model in biomedical
      studies. Efficient and precise modification of pig genome by using recently
      developed gene editing tools has significantly broadened the application of pig
      models in various research areas. The three types of site-specific nucleases,
      namely, zinc-finger nucleases, transcription activator-like effector nucleases,
      and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated protein, are the main gene editing tools that can efficiently
      introduce predetermined modifications, including knockouts and knockins, into the
      pig genome. These modifications can confer desired phenotypes to pigs to improve
      production traits, such as optimal meat production, enhanced feed digestibility,
      and disease resistance. Besides, given their genetic, anatomic, and physiologic
      similarities to humans, pigs can also be modified to model human diseases or to
      serve as an organ source for xenotransplantation to save human lives. To date,
      many genetically modified pig models with agricultural or biomedical values have
      been established by using gene editing tools. These pig models are expected to
      accelerate research progress in related fields and benefit humans.

PMID- 30233646
TI  - Genomic Prediction of Complex Phenotypes Using Genic Similarity Based Relatedness
      Matrix.
AB  - In the last years, a series of methods for genomic prediction (GP) have been
      established, and the advantages of GP over pedigree best linear unbiased
      prediction (BLUP) have been reported. However, the majority of previously
      proposed GP models are purely based on mathematical considerations while seldom
      take the abundant biological knowledge into account. Prediction ability of those
      models largely depends on the consistency between the statistical assumptions and
      the underlying genetic architectures of traits of interest. In this study, gene
      annotation information was incorporated into GP models by constructing haplotypes
      with SNPs mapped to genic regions. Haplotype allele similarity between pairs of
      individuals was measured through different approaches at single gene level and
      then converted into whole genome level, which was then treated as a special
      kernel and used in kernel based GP models. Results shown that the gene annotation
      guided methods gave higher or at least comparable predictive ability in some
      traits, especially in the Arabidopsis dataset and the rice breeding population.
      Compared to SNP models and haplotype models without gene annotation, the gene
      annotation based models improved the predictive ability by 0.56~26.67% in the
      Arabidopsis and 1.62~16.53% in the rice breeding population, respectively.
      However, incorporating gene annotation slightly improved the predictive ability
      for several traits but did not show any extra gain for the rest traits in a
      chicken population. In conclusion, integrating gene annotation into GP models
      could be beneficial for some traits, species, and populations compared to SNP
      models and haplotype models without gene annotation. However, more studies are
      yet to be conducted to implicitly investigate the characteristics of these gene
      annotation guided models.

PMID- 30233650
TI  - Rotation coordinating device for improving condylar guidance settings of nonarcon
      articulators: Part 1.
AB  - Background: Setting of condylar inclination is inaccurate in nonarcon
      articulators because of alteration of the angle between the upper member and
      condylar track. This article presents a device which can be attached to a
      nonarcon articulator to rectify errors related to alterations of maxillary
      occlusal plane-horizontal condylar guidance relation in nonarcon articulators.
      Materials and Methods: The device provides tight connection of condylar axis to
      condylar track by mechanical interdigitation of fragments which are placed on
      condylar axis and condylar track. Condylar track rotates coordinated with
      condylar axis. Fragments consist of medial fragments placed on medial surface of
      articular fossa analogs, lateral fragments placed on lateral surface of articular
      fossa analogs, and condylar axis fragments placed on condylar axis. The device
      can be used during condylar inclination adjustment by interocclusal records,
      changing vertical dimension of occlusion, and occlusal adjustment of
      restorations. Initial evaluation of the device was performed during an opening
      hinge movement in a single experiment. The angle between condylar track and the
      upper member of the articulator was determined by calculation before and after
      applying hinge movement and with and without the device. Results: When the device
      was not used, the postexperimental condylar inclination was 7.31 degrees  higher
      than preexperimental value. Using the device, discrepancy reached 2.17 degrees .
      Conclusion: Using this device may lead to more accurate condylar inclination
      adjustment which is followed by more accurate prosthetic teeth.

PMID- 30233649
TI  - Comparison of sealing ability of ProRoot mineral trioxide aggregate, biodentine,
      and ortho mineral trioxide aggregate for canal obturation by the fluid
      infiltration technique.
AB  - Background: Adequate seal of the root canal is necessary to prevent
      recontamination and ensure the long-term clinical success. The aim of this study
      was to evaluate the sealing ability of ProRoot mineral trioxide aggregate (MTA),
      Biodentine, and Ortho MTA as the root canal obturation materials using the fluid
      infiltration method. Materials and Methods: In this invitro study a total of 66
      extracted human mandibular premolars were randomly divided into five groups
      according to the material used for the root canal obturation. Group I - ProRoot
      MTA (20 samples), Group II - Biodentine (20 samples), Group III - Ortho MTA (20
      samples), Group IV - negative group (3 samples), and Group V-positive group (3
      samples). MTA, Biodentine, and Ortho MTA were applied using a cotton-tipped K
      file #30 and hand plugger into the root canals of each group. In Group 4
      (negative control), no filling material was used. In Group 5 (positive control),
      a single gutta-percha size #40 was inserted into the root canal without using a
      sealer. The teeth were mounted and exposed to the fluid infiltrarion system.
      Statistical analysis was performed using Kruskal-Wallis test the level of
      significance was set at alpha = 0.05. Results: Mean values of microleakage in MTA
      ProRoot, Biodentine and Ortho MTA groups were 1.83 +/- 0.62, 1.95 +/- 1.27 and
      1.72 +/- 0.83 MUL in 8 minutes. No statistically significant difference was
      observed between the sealing ability of ProRoot MTA, Biodentine, and Ortho MTA (P
      = 0.091). Conclusion: Within the limitations of this study, microleakage values
      were similar to MTA ProRoot, Biodentine, and Ortho MTA using the fluid
      infiltration technique.

PMID- 30233651
TI  - Efficacy of diode laser irradiation during dental bleaching in preventing enamel
      damage caused by bleaching.
AB  - Background: Evidence on the protecting effect of laser on bleached enamel is
      scarce and controversial. Therefore, we aimed to test for the first time whether
      different wavelengths of diode laser (810 and 980 nm) can prevent enamel surface
      corrosion. We also tested for the first time whether such therapeutic effects of
      laser are limited to specific "laser-activated" bleaching gels or both
      conventional and laser-activated gels. Materials and Methods: In this qualitative
      experimental study, ten intact human teeth were randomly assigned to five Groups.
      They were sectioned into twenty buccal/lingual pieces. The groups were: (1) laser
      activated gel + 810 nm laser, (2) laser-activated gel + 980 nm laser, (3)
      conventional gel + 810 nm laser, (4) conventional gel + 980 nm laser, (5)
      conventional gel only, and (6) laser-activated gel - no irradiation. Buccal
      sections in each group were subjected to bleaching (according to the stated
      protocols), and later subjected to field-emission scanning electron microscopy
      (SEM) and X-ray diffraction (XRD). The lingual pieces were used as "before
      treatment" negative controls for XRD. Results: XRD showed an increase in the
      mineral phase and crystallinity of the enamel in all bleaching groups. This was
      stronger in the laser-irradiated groups with conventional bleaching agent. SEM
      showed a complete etched surface in the positive control groups (i.e., bleached
      using conventional agent). However, all four laser groups had almost intact
      surfaces. Conclusion: This study showed the positive effect of diode laser
      irradiation at 810 nm or 980 nm wavelengths on the prevention of bleaching
      damage, irrespective of the activation mechanism of the bleaching gel in use.

PMID- 30233652
TI  - Effect of Sudarshan Kriya Pranayama on periodontal status and human salivary beta
      defensin-2: An interventional study.
AB  - Background: Yogic stretching (asana) has been proven to have an effect on
      salivary human beta-defensin-2 (HBD-2) concentration, which is an antimicrobial
      peptide and is an inflammatory marker in periodontal disease. Sudarshan Kriya
      Pranayama (SKP) is a part of yoga which involves rhythmic breathing. Hence, we
      aim to evaluate the periodontal parameters and to estimate the salivary HBD-2
      level before and after SKP program in periodontitis individuals. Materials and
      Methods: An interventional study was designed and individuals were divided into
      three groups: Group I - healthy periodontium, Group II - chronic gingivitis, and
      Group III - chronic periodontitis. SKP was the interventional tool. The clinical
      parameters such as plaque index (PI), gingival index (GI), probing pocket depth
      (PPD), clinical attachment level (CAL), and salivary HBD-2 level were analyzed at
      baseline and 90 days after the SKP practice. Enzyme-linked immunosorbent assay
      (ELISA) was used to evaluate salivary HBD-2. McNemar's Chi-square, Paired samples
      t-test, and one-way ANOVA were used to analyze the results. P < 0.05 was
      considered statistically significant. Results: Following the SKP intervention,
      the clinical parameters such as PI and GI improved significantly in all the
      groups (P < 0.001); however, Group III showed a significant reduction as compared
      to the other groups. The mean baseline salivary HBD-2 levels of Group I, Group
      II, and Group III were 91.78 ng/MUl, 110.22 ng/MUl, and 157.63 ng/MUl which was
      further decreased to 95.22 ng/MUl, 98.22 ng/MUl, and 132.88 ng/MUl, respectively,
      following SKP intervention (P < 0.001). However, Group III had a higher HBD-2
      level at 90 th day as compared to other groups. Conclusion: There was an
      improvement in PI and GI with a decrease in salivary HBD-2 in chronic
      periodontitis patients following SKP. Hence, SKP can be considered as an adjunct
      to treatment modality in patients with periodontal disease.

PMID- 30233653
TI  - DNA profiling of Streptococcus mutans in children with and without black tooth
      stains: A polymerase chain reaction analysis.
AB  - Background: The purpose of this study was to identify the genetic patterns of
      Streptococcus mutans by DNA finger printing among caries-active, caries-free, and
      in children with black tooth stains. Materials and Methods: In this in vitro
      study Ten children with black tooth stains and ten caries-free and caries-active
      children between 3 and 6 years of age were recruited. Saliva samples were
      collected using a sterile tube, followed by microbial culture of S. mutans, DNA
      isolation, and polymerase chain reaction amplification. The molecular weights of
      each band were converted into binary data, and data were entered into SPSS to
      generate similarity dendrograms. Results: Dendrogram interpretation of black
      tooth stain and caries-free samples revealed an identical genetic pattern in 15
      samples with high genetic similarity. Dendrogram interpretation of black tooth
      stain and caries-active samples exhibited a greater genetic diversity.
      Conclusion: This study concludes that identical genotypes and high genetic
      similarity among isolates of the caries-free and black tooth stains. Polymorphism
      and genetic diversity exist between the black tooth stain and caries-active
      samples.

PMID- 30233654
TI  - In vitro comparison of the effects of microwave irradiation and chemical and
      mechanical methods on the disinfection of complete dentures contaminated with
      Candida albicans.
AB  - Background: Dentures can be a source of infection or cross-contamination with
      microorganisms like Candida albicans. The aim of this in vitro study was to
      compare the effects of microwave irradiation, chemical techniques, and a
      mechanical method (i.e., brushing) on the disinfection of complete dentures
      contaminated with C. albicans. Materials and Methods: In this experimental study,
      sixty sterilized dentures were divided into six groups of 10 dentures each. The
      dentures in Groups 1 and 6 served as negative and positive controls,
      respectively. The dentures (Groups 2-5) were contaminated with C. albicans and
      subjected to four disinfection procedures: Corega tablets, 2% glutaraldehyde,
      brushing, and microwave irradiation. Replicate aliquots (25 mL) of the suspension
      were cultured in Sabouraud dextrose broth. The colonies were counted after 48 h
      of incubation at 37 degrees C. To confirm long-term disinfection, the Trypticase
      soy broth (TSB) containers were stored at 37 degrees C for 7 days, and turbidity
      was visually observed. Data were analyzed with one-way ANOVA and independent
      samples t-test on SPSS the level of statistical significance was set at 0.05.
      Results: The dentures disinfected with microwave irradiation (650 W, 3 min) and
      glutaraldehyde (2%, 10 min) exhibited no evidence of fungal growth after 48 h of
      incubation and also no turbidity in the TSB containers after 7 days of
      incubation. However, the dentures disinfected using the mechanical method and
      Corega tablets exhibited turbidity after 7 days and fungal growth after 48 h that
      was significantly more than that in the two other methods (P = 0.000) and less
      than that in the positive control group (P = 0.000). The differences between
      mechanical cleaning and cleansing tablet were not significant (P = 0.017).
      Conclusion: Base on the results of this study, microwave irradiation (650 W, 3
      min) and 2% glutaraldehyde completely disinfected the dentures contaminated with
      C. albicans in the short term and long term.

PMID- 30233655
TI  - The effect of microthread design on magnitude and distribution of stresses in
      bone: A three-dimensional finite element analysis.
AB  - Background: The researches regarding the influence of microthread design
      variables on the stress distribution in bone and a biomechanically optimal design
      for implant neck are limited. The aim of the present study is to compare the
      effect of different microthread designs on crestal bone stress. Materials and
      Methods: Six implant models were constructed for three-dimensional finite element
      analysis including two thread profile (coarse and fine) with three different
      lengths of microthreaded neck (1 mm, 2 mm, and 3 mm). A load of 200 N was applied
      in two angulations (0 degrees  and 30 degrees ) relative to the long axis of the
      implant and the resultant maximum von Mises equivalent (EQV), compressive,
      tensile, and shear stresses were measured. Results: Regardless of loading angle,
      the highest EQV stress was concentrated in the cortical bone around the implant
      model using a 1 mm neck of fine microthreads. Under axial loading, there was a
      negative correlation between the length of the microthreaded neck and stress
      level in both profiles. However, the same pattern was not observed for coarse
      microthreads under oblique loads. All types of measured stresses in all
      constructed models were increased with oblique loading. Conclusion: Peak stress
      levels in implant models varied with microthread profile and direction of
      loading. The microthread profile seemed more important than the length of the
      neck in reducing loading stresses exerted on the surrounding bone. Fine
      microthreads on a 3 mm implant neck showed consistently higher cortical bone
      stress than other models.

PMID- 30233656
TI  - Evaluation of the effect of diode laser for debonding ceramic brackets on
      nanomechanical properties of enamel.
AB  - Background: The heat from laser can lead to the destruction of organic components
      of enamel and consequently changes in the mechanical properties of enamel. The
      purpose of this study was to evaluate the effect of diode laser on the
      nanomechanical properties of enamel in the process of debonding the ceramic
      brackets. Materials and Methods: In This in vitro study Eighteen ceramic brackets
      were bonded on the intact premolars in 3 groups of 6 (one control and two study
      groups). To debond the brackets in the study groups, laser diode was used for 3 s
      with 1W and 3W power. Shear bond strength and adhesive remnant index were
      recorded for all groups. Hardness and elastic modulus were measured in 1-31 MU
      depth from enamel surface in each debonded area. Analysis of variance was used
      for determining the difference in shear bond strength (SBS), hardness, and
      elastic modulus and was followed by post hoc Tukey's honest significant
      difference test. One-sample t-test was used to compare the changes in the pulp
      temperature with the standard threshold (5.5 degrees C). The significance level
      was set at %5 in this study. Results: SBS was significantly greater in the
      control group compared to the study groups. There was no significant difference
      in the average of hardness and elastic modulus of enamel between the groups. Pulp
      temperature elevation in the study groups was significantly < 5.5 degrees C (P =
      0.000). Conclusion: The diode laser with either 1W or 3W power for 3 s is
      effective in debonding the ceramic brackets without any detrimental effect on the
      pulp or mechanical properties of enamel. In regard to the pulp health, the 1W
      power laser is rather recommended for debonding the ceramic brackets than the 3W
      laser power.

PMID- 30233658
TI  - Evaluation of the relationship between pH and titrable acidity of five different
      of iron supplements with the absorption of iron ions in the anterior primary
      teeth (an in vitro study).
AB  - Background: Iron supplement is recommended for alleviating iron deficiency. Black
      discoloration of teeth is one of the side effects of consumption of iron
      supplements. Besides these effects, iron drops may also act directly on the
      dental hard tissues, with erosive lesions as possible outcomes of their content.
      In this regard, we decided to compare iron absorption of five types of iron drops
      in enamel and determine its relationship with pH and titrable acidity (TA) of
      them. Materials and Methods: In this in-vitro study The pH of 5 kinds of iron was
      measured by a digital pH meter. Each drop was titrated and then the TA was
      calculated. For this experimental study, 40 healthy anterior primary teeth were
      prepared and divided into 5 groups then exposed to iron drops. The level of iron
      absorption was determined by atomic absorption. The Pearson correlation test was
      used to analysis correlations between pH, TA, and absorption of iron ions in the
      anterior primary teeth. One-way ANOVA was used for statistical analysis.
      Statistical significance was set at P < 0.05. Results: The mean of pH in Kharazmi
      drops was significantly less than both Irovit, and FerroKids drops (P < 0.05) but
      did not differ significantly with other drops. Kharazmi drops TA was higher than
      all drops (P < 0.05). There was no significant difference between the mean iron
      ion adsorption, as well as between iron ion absorption with pH and TA also not
      found a statistically significant relationship. Conclusion: All drops have acidic
      content that increases their potential for erosion. Reducing the potential of the
      effects of iron drops on dental hard tissues should be of concern to all health
      professionals.

PMID- 30233657
TI  - CD44 expression in pleomorphic adenoma, carcinoma ex pleomorphic adenoma and
      their adjacent normal salivary glands.
AB  - Background: CD44 is a transmembranous proteoglycan, with a main role of cell
      adhesion to other cells and to extracellular matrix involved in the preservation
      of three-dimensional structure of organs. Pleomorphic adenoma (PA) is a common
      benign salivary gland tumor, composed of myoepithelial and ductal components.
      Carcinoma ex-PA (CXPA) is malignant transformation of the epithelial elements in
      PA. The aim of this study was to evaluate CD44 expression by immunohistochemistry
      in these two tumors and normal salivary gland near these tumors. Materials and
      Methods: In this cross-sectional immunohistochemical study, 40 paraffin blocks
      (formalin fixed, paraffin embedded) with thirty belonging to PA and ten blocks of
      CXPA and 18 paraffinized blocks of normal salivary glands' tissue adjacent to
      tumoral tissue (13 in the vicinity of PA and 5 in the vicinity of CXPA) were
      selected. Immunohistochemical expression of CD44 was observed and compared with
      each other. For data analysis, we used Chi-square, Kruskal-Wallis, and Mann
      Whitney tests and the quantity of P values was considered 0.05. Results: There
      was a significant difference in CD44 expression frequency between PA, CXPA, and
      normal salivary glands with higher expression noted in CXPA. Furthermore,
      expression frequency of CD44 in adjacent normal salivary gland of CXPA was
      significantly higher than PA. There was no significant difference in the
      expression of CD44 with respect to lymph node metastasis. Conclusion: Higher
      expression of CD44 in CXPA might illustrate CD44's role in malignant
      transformation of PA.

PMID- 30233659
TI  - Unusual report of non-syndromic permanent unilateral mandibular canine agenesis.
AB  - Nonsyndromic unilateral permanent canine agenesis, particularly in the lower jaw,
      is an infrequent clinical observation that has occasionally been reported in the
      scientific literature. The main aim of the present case report and study is to
      give insights into the clinical features and genetic information of a
      nonsyndromic patient affected by unilateral lower canine agenesis and her
      relatives. A young girl of 9-year-old with a Class II skeletal malocclusion,
      sella turcica bridging, and severe overjet but no other dental anomalies is
      described. No associations were found with other types of dental agenesis and
      previously described genetic variations of the CTNNB1 gene. The possibility of a
      novel genetic locus should be considered as a possible genetic etiology for this
      extremely rare condition in a nonsyndromic patient. Based on scientific
      literature written in English, the present clinical case is one of the first
      reports to describe a nonsyndromic permanent unilateral mandibular canine
      agenesis.

PMID- 30233660
TI  - Barriers and facilitators to treatment among patients with newly diagnosed
      hypertension in Nepal.
AB  - Objective: Hypertension is a significant and rising burden in Nepal. The disease
      remains undetected and inadequately managed. However, no studies have been
      conducted to understand the inhibiting and facilitating factors to hypertension
      treatment among newly diagnosed cases. This qualitative study aimed to explore
      barriers and facilitators to treatment among patients with newly diagnosed
      hypertension aged >=18 years in Dhulikhel, Nepal. Methods: We conducted seven
      focus group discussions with 35 patients with newly diagnosed hypertension
      identified through community surveillance of the Dhulikhel Heart Study, an
      observational cohort of Dhulikhel Hospital, Kathmandu University. Audiotaped
      discussions were transcribed, inductively coded and analysed by the thematic
      framework method using Atlas.ti V.7. Results: Hypertension was viewed as a rising
      problem in the community. Participants had limited knowledge and many misbeliefs
      regarding hypertension and its treatment. The major barriers included absence of
      symptoms, reluctance to take medicine, low perceived seriousness of the disease,
      challenges in behaviour change (diet and exercise), lack of family support, and
      lack of communication and trust with the provider. The major reported
      facilitating factors were fear of consequences of the disease, and family support
      in controlling diet and adhering to treatment. Conclusions: A number of factors
      emerged as barriers and facilitators to hypertension treatment. This information
      can be useful in designing appropriate health interventions to improve
      hypertension management.

PMID- 30233661
TI  - Percutaneous closure of iatrogenic arteriovenous fistula after pacemaker
      implantation.

PMID- 30233662
TI  - CYP24A1 depletion facilitates the antitumor effect of vitamin D3 on thyroid
      cancer cells.
AB  - It has been demonstrated that 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1) is a
      key enzyme that neutralizes vitamin D activity, which may have an anti-tumor
      effect. Therefore, the aim of the current study was to explore the effect of the
      active metabolite of vitamin D, 1,25-dihydroxyvitamin D (1,25-D3) on thyroid
      cancer cells following the downregulation of CYP24A1. A Cell Counting Kit-8 assay
      identified that CYP24A1 knockdown enhanced the anti-proliferative effects of 1,25
      D3 on thyroid cancer cells. Furthermore, the results of the scratch wound and
      Transwell assays indicated that CYP24A1 knockdown enhanced the inhibitory effect
      of 1,25-D3 on cell migration. The results from reverse transcription-quantitative
      polymerase chain reaction and western blot analysis indicated that treatment with
      1,25-D3 and CYP24A1 knockdown synergistically enhanced the expression of the
      epithelial-related gene E-cadherin and decreased the expression of the
      mesenchymal-related genes N-cadherin and vimentin. Following CYP24A1 knockdown
      and treatment with 1,25-D3, the expression of matrix metalloproteinase 2 and
      metalloproteinase inhibitor 1 were significantly decreased and increased,
      respectively, compared with the group that underwent treatment with 25-D3 alone.
      Furthermore, protein kinase B (Akt) and beta-catenin activity was significantly
      decreased by this synergetic effect compared with the group that underwent
      treatment with 1,25-D3 alone. The results of the current study suggest that
      CYP24A1 knockdown contributes to the anti-tumor effect of 1,25-D3 and that this
      effect may be due to deactivation of the Akt and beta-catenin signaling pathways.
      Therefore, CYP24A1 knockdown and 1,25-D3 treatment may be used synergistically as
      a novel therapeutic strategy to treat patients with thyroid cancer.

PMID- 30233663
TI  - MicroRNA-139-5p elevates skeletal myogenic differentiation of human adult dental
      pulp stem cells through Wnt/beta-catenin signaling pathway.
AB  - The aim of the present study was to identify a microRNA (miRNA or miR)-based
      biomarker and therapeutic target for skeletal myogenic differentiation of human
      adult dental pulp stem cells (ADSCs). miRNA expression was measured using reverse
      transcription-quantitative polymerase chain reaction; cell viability assay and
      lactate dehydrogenase (LDH) activity levels were measured using MTT and LDH
      activity kits, respectively. Apoptosis assay and caspase-3/9 activity levels were
      measured using flow cytometry and caspase-3/9 activity kits, respectively.
      Western blot analysis and immunofluorescence microscopy measured the protein
      expression of myocyte-specific enhancer factor 2C, myogenic differentiation 1,
      myosin heavy chain, Wnt and beta-catenin. Overexpression of miR-139-5p promoted
      cell growth and induced skeletal myogenic differentiation of ADSCs.
      Downregulation of miR-139-5p inhibited cell growth and reduced skeletal myogenic
      differentiation of ADSCs. Overexpression of miR-139-5p induced Wnt/beta-catenin
      signaling pathway and Wnt/beta-catenin signaling pathway was suppressed by anti
      miR-139-5p in ADSCs. Wnt inhibitor reduced the effect of miR-139-5p on skeletal
      myogenic differentiation of ADSCs. In conclusion, miR-139-5p elevates skeletal
      myogenic differentiation of human ADSCs through the Wnt/beta-catenin signaling
      pathway.

PMID- 30233665
TI  - Expression of c-Myc and Beclin-1 in skin of rats after burn.
AB  - This study aimed to investigate the expression features of Beclin-1 and c-Myc in
      the skin burn of rats. A total of 48 Sprague-Dawley (SD) rats were randomly
      divided into the normal group (n=12), the 3-day burn group (n=12), the 5-day burn
      group (n=12) and the 7-day burn group (n=12). Except for the normal group, the
      rat models of burn were established in the other three groups, burn wounds were
      given routine dressing change, and rats were sacrificed at 3, 5 and 7 days after
      modeling to collect materials. Then, immunohistochemistry was applied to detect
      the expression of c-Myc and Beclin-1. The expression levels of c-Myc protein and
      Beclin-1 protein were measured via western blotting. The expression levels of c
      Myc messenger ribonucleic acid (mRNA) and Beclin-1 mRNA were detected by reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR). In comparison
      with the normal group, three burn groups had significantly increased the
      expression of c-Myc and Beclin-1, and the differences were statistically
      significant (P<0.05). Beclin-1 expression in the 5-day burn group was obviously
      higher than those in the 3 and 7-day burn groups, and the differences were of
      statistical significance (P<0.05). The expression of c-Myc in the 7-day burn
      group was overtly higher than those in the 3 and 5-day burn groups, and the
      differences showed statistical significance (P<0.05). The expression of Beclin-1
      and c-Myc in post-burn skin tissues were gradually increased, with the Beclin-1
      expression level reaching the peak on the 5th day after burn, and the expression
      level of c-Myc was the highest on the 7th day after burn.

PMID- 30233664
TI  - Effect of simvastatin on expression of VEGF and TGF-beta1 in atherosclerotic
      animal model of type 2 diabetes mellitus.
AB  - Expression of vascular endothelial growth factor (VEGF) and transforming growth
      factor-beta1 (TGF-beta1) in atherosclerosis animal model of type 2 diabetes
      mellitus treated with simvastatin was investigated. Clean grade mature Sprague
      Dawley (SD) rats were divided into three groups: Normal control (n=10), model
      (n=13) and treatment group (n=13); low-dose simvastatin was administered. The
      changes of VEGF and TGF-beta1 levels were analyzed by tail vein blood sampling.
      The relationship between levels of VEGF, TGF-beta1 and treatment time was
      analyzed. The expression level of VEGF in the treatment group after 4 and 8 weeks
      of intervention was lower compared with the model group (P<0.05). The expression
      level of TGF-beta1 in the treatment group after 8 weeks of intervention was
      higher than that in the model group (P<0.05). The expression level of VEGF in the
      treatment group after 8 weeks of intervention was lower than that after 1 week of
      intervention (P<0.05). The expression level of TGF-beta1 was increased in the
      model group after 8 weeks of intervention compared with 1 week before and after
      the intervention (P<0.05). The expression level of TGF-beta1 in the treatment
      group at 2, 4 and 8 weeks after intervention were significantly higher than that
      before intervention (P<0.05). The expression of TGF-beta1 increased after 4 and 8
      weeks after intervention compared with 1 week after intervention (P<0.05). The
      expression of VEGF was negatively correlated with TGF-beta1 expression in the
      treatment group; negative correlation was found between VEGF and treatment time.
      There was a positive correlation between TGF-beta1 and treatment time. VEGF and
      TGF-beta1 may be involved in the development of type 2 diabetes (T2MD)
      atherosclerosis (AS). Simvastatin may play a therapeutic role in T2MD AS by
      downregulating VEGF and upregulating the expression of TGF-beta1.

PMID- 30233666
TI  - Exercise intervention alleviates nerve injury by the suppression of inflammatory
      mediator expression via the TLR4/NF-kappaB signaling pathway.
AB  - Spinal cord injury (SCI) may cause changes that have damaging effects on
      sensation and functionality. However, methods for the significant amelioration of
      SCI-reduced nerve injury are lacking. Previous studies have indicated that
      reasonable and effective exercise may promote the recovery of injured nerves.
      Therefore, the aim of the present study was to investigate the ability of
      exercise to improve recovery following SCI and the underlying mechanism. A rat
      model was used to evaluate the effects of two different periods of exercise
      intervention on recovery following SCI. The exercise intervention comprised 15 or
      30 min/day passive walking for 30 days. ELISA measurements were used to analysis
      the plasma levels of inflammatory cytokines. Reverse transcription-quantitative
      polymerase chain reaction and western blot analyses were performed to examine the
      levels of proteins and mRNAs associated with nuclear factor (NF)-kappaB-related
      signaling. In addition, histological examination and immunostaining were used to
      evaluate the neural injury and associated indicators. The results indicated that
      severe SCI induced a peripheral inflammatory response and increased the
      expression of inflammatory cytokines. In addition, the SCI-induced nerve injury
      was associated with increased glial fibrillary acidic protein (GFAP) expression
      and the upregulation of Toll-like receptor 4 (TLR4)/NF-kappaB signaling, which
      may further aggravate the inflammatory responses induced by SCI. However, the
      exercise intervention decreased SCI-induced GFAP expression and reduced the
      activation of the TLR4/NF-kappaB signaling pathway compared with that of SCI
      model rats that did not exercise. Furthermore, the exercise intervention
      inhibited the release of inflammatory cytokines into the serum. These results
      indicate that exercise treatment reduces inflammation and glial activation, and
      may be beneficial to recovery following SCI.

PMID- 30233668
TI  - Propofol-induced vasodilation of mesenteric arterioles via BKCa channel and gap
      junction.
AB  - The present study aimed to investigate the role of propofol in mediating the
      vasomotor activity of the mesenteric arteriole (MA) of Sprague Dawley (SD) rats,
      and to elucidate the underlying mechanisms. The pressure myograph technique was
      used to examine the effect of different concentrations of propofol on the
      relaxation of blood vessels in the 2-3 mm MA segments freshly separated from the
      SD rats. The whole-cell patch-clamp technique was applied to observe the outward
      current of single vascular smooth muscle cells (VSMCs) obtained from the MAs of
      the SD rats. Furthermore, immunofluorescence was utilized to assess the
      expression of connexin (Cx) in the MAs of SD rats. The results indicated the
      following: i) Propofol relaxed the MA of SD rats in a concentration-dependent
      manner from 1*10-7 to 3*10-4 mol/l; ii) in the acutely dissociated VSMCs,
      propofol (1*10-7 to 3*10-4 mol/l) enhanced the outward current of VSMCs in a
      concentration-dependent manner; iii) the enhanced outward currents induced by
      propofol (1*10-5 mol/l) may be reversed by tetraethylammonium (TEA; 1 mmol/l), a
      calcium-activated K+ channel inhibitor; iv) the effect of propofol on the
      relaxation of the vasculature wAS reduced after perfusion with 1 mmol/l TEA; v)
      Cx40, Cx43 and Cx45 were expressed on the MA; 6) 18beta-glycyrrhetintic acid and
      2-aminoethoxydiphenyl borate, two types of gap junction blocker, inhibited the
      propofol-induced relaxation. The present study provides evidence that propofol
      relaxes the MA, which may be associated with its effect of enhancing the channel
      current of large-conductance calcium voltage-activated potassium channels,
      contributing to the K+ outflow and leading to VSMC hyperpolarization; the gap
      junction may facilitate the hyperpolarization, which may lead to vascular
      synchronized relaxation and thereby reduce the blood pressure.

PMID- 30233667
TI  - Impact of phosphorylated insulin-like growth factor-1 receptor on the outcome of
      breast cancer patients and the prognostic value of its alteration during
      neoadjuvant chemotherapy.
AB  - The expression of insulin-like growth factor-1 receptor (IGF-1R), which is
      involved in the genesis and progression of breast cancer, is thought to be
      associated with the overall survival (OS) of patients. However, the predictive
      and prognostic significance of the IGF-1R expression in breast cancer remains
      controversial. The present study aimed to identify the factors associated with
      the levels of phosphorylated (p)-IGF-1R in breast cancer, their impact on the
      outcomes of breast cancer patients, and the prognostic value of alterations of p
      IGF-1R during neoadjuvant chemotherapy (NAC). The present study included 348
      female breast cancer patients whose paraffin-embedded tumor tissue sections had
      been collected by biopsy and/or resection, among which the pre-NAC and post-NAC
      sections were available from 40 patients. Human epidermal growth factor receptor
      2 (HER2) positivity and molecular subtype were significantly associated with the
      presence of p-IGF-1R in the tumor tissue (P<0.05). Patients with p-IGF-1R present
      in the tumor tissue had a shorter OS (P=0.003). The p-IGF-1R levels in the tumor
      after NAC differed significantly from those prior to NAC (P=0.005); however, this
      alteration in p-IGF-1R levels was not associated with a shorter OS. In parallel
      with HER2, p-IGF-1R appears to be a promising indicator for predicting clinical
      outcomes and may be an attractive target for improving the efficacy of antitumor
      therapy, particularly for patients with HER2-negative, estrogen receptor-positive
      and luminal B tumors.

PMID- 30233669
TI  - Eosinophilic cystitis in children: A case report.
AB  - The aim of the present case report was to investigate the clinical features,
      pathological examination and treatment of eosinophilic cystitis (EC) in children.
      Two cases of EC were reported and reviewed from January 2016 to March 2017. Case
      1 (male; 6 years old) had intermittent hematuria, frequent urination, urgent
      urination, difficulty in urination and abdominal pain. Case 2 (male; 7 years old)
      had frequent urination, urgent urination, urinary pain, dysuria and suprapubic
      pain with no hematuria. One patient had a history of allergies and both patients
      underwent a cystoscope biopsy. Blood eosinophils were clearly increased and a
      bone marrow biopsy examination revealed that marrow eosinophils were also
      increased in both cases. The urine culture results were negative. Ultrasonography
      and computed tomography revealed uneven thickening of the bladder wall and
      diffusive mucosal lesions. Cystoscopy revealed that the bladder volume became
      smaller and the mucosa at the bladder floor and neck was red. Lesions were
      biopsied through the urethra and the following characteristics were observed:
      Congestion and edema of the bladder mucosa, infiltration of the blood vessels and
      eosinophils in the muscular layer, accompanied by focal muscle necrosis. Patient
      1 was administered anti-inflammatory and cetirizine hydrochloride treatments,
      followed by 6 weeks of prednisone dose-reduction therapy. Patient 2 was
      administered antibiotics and cetirizine hydrochloride. Following 6-month follow
      ups, abnormal voiding symptoms had disappeared in each case. Ultrasonography and
      computed tomography revealed no bladder wall thickening or space-occupying
      lesions. EC in children is rare and easily misdiagnosed as nonspecific bladder
      inflammation or bladder occupying lesions. Cystoscopy and biopsy are necessary to
      diagnose EC and conservative treatments with anti-inflammatory, anti-allergic and
      cortical hormone nonspecific treatments are suggested.

PMID- 30233670
TI  - Diagnostic value of platelet-derived microparticles in pulmonary thromboembolism:
      A population-based study.
AB  - An early and accurate diagnosis of pulmonary thromboembolism (PTE) remains
      challenging. The present study aimed to evaluate the diagnostic value of platelet
      derived microparticles in PTE based on a population study. A total of 102
      patients with PTE, 102 healthy controls and 40 patients suspected with PTE were
      enrolled in this study. The platelet count, mean platelet volume and platelet
      distribution width were assessed using an automated hematology analyzer, P
      selectin was assessed using an ELISA kit and PMPs were explored using flow
      cytometry using Megamix beads. Receiver operating characteristic curves were
      established to evaluate the diagnostic values of PMPs, D-dimer, PMPs combined
      with D-dimer, and multiple parameters (including PMPs, platelet distribution
      width, P-selectin and D-dimer in PTE). The PMP levels were significantly higher
      in the patients with PTE (609.10/ul) compared with those in the healthy controls
      (230.60/ul) and patients with suspicious PTE (166.70/ul; P<0.01). The accuracy
      (72.06%) of PMPs in the diagnosis of PTE was similar to those of D-dimer
      (P>0.05). The combination of D-dimer and PMPs significantly increased the
      sensitivity (86.27%) of D-dimer and the specificity of PMP for the diagnosis of
      PTE (P<0.01). The combination of PMPs, platelet distribution width, P-selectin
      and D-dimer exhibited high sensitivity (88.24%), specificity (91.18%) and
      accuracy (89.71%) in the diagnosis of PTE. These findings suggest that elevated
      PMP levels are an effective predictor of PTE. The combination of PMPs, platelet
      distribution width, P-selectin and D-dimer may be used in the diagnosis of PTE
      with high sensitivity and specificity.

PMID- 30233671
TI  - Predicative values of C-reactive protein for the therapeutic effects of
      ulinastatin combined with somatostatin in severe acute pancreatitis and for the
      severity of gastrointestinal failure.
AB  - Severe acute pancreatitis (SAP) is a serious systemic disease with high
      mortality. Ulinastatin is a drug widely used for patients with SAP and multiple
      organ failure syndrome. The present study aimed to investigate the capacity of
      the serum C-reactive protein (CRP) levels to predict the therapeutic effects of
      ulinastatin combined with somatostatin as well as determine the severity of SAP.
      SAP patients were treated with ulinastatin combined with somatostatin and serum
      CRP levels were measured. The computed tomography severity index (CTSI), acute
      physiology and chronic health evaluation II (APACHE II) and gastrointestinal
      failure scores were used to determine the therapeutic effects. All patients were
      assigned to the effective group and the ineffective group. Receiver operating
      characteristic curve analysis was performed to determine the sensitivity and
      specificity of CRP levels in predicting the severity of SAP and patient
      prognosis. Logistic regression analysis was adopted to investigate the factors
      influencing the therapeutic effects. Prior to and after treatment, serum CRP
      levels in patients of the effective and ineffective groups were significantly
      different. After treatment, serum CRP levels in patients of the effective group
      exhibited a more obvious reduction. The sensitivity and specificity of serum CRP
      levels in predicting the therapeutic effects of ulinastatin combined with
      somatostatin in SAP patients upon hospital admission were 0.813 and 0.934,
      respectively. Serum CRP levels were positively correlated with APACHE II, CTSI
      and gastrointestinal failure scores of SAP patients. The logistic regression
      demonstrated that serum albumin, creatinine and CRP levels on admission were
      factors influencing the therapeutic effects of ulinastatin combined with
      somatostatin in SAP patients. These results indicate that serum CRP levels may
      have a predictive value regarding the therapeutic effects of ulinastatin combined
      with somatostatin and are an indicator of the severity of gastrointestinal
      failure in SAP.

PMID- 30233672
TI  - SPARCL1 suppresses the proliferation and migration of human ovarian cancer cells
      via the MEK/ERK signaling.
AB  - Ovarian cancer is the most lethal gynecological malignancy worldwide and is one
      of the five leading causes of cancer-associated mortality in women. There is an
      urgent requirement to obtain a greater understanding of the molecular mechanism
      underlying ovarian cancer progression in order to identify novel drug targets and
      biomarkers. Secreted protein acidic and rich in cysteine-like protein 1 (SPARCL1)
      has been suggested as a candidate tumor suppressor in various types of human
      cancers. However, the potential role of SPARCL1 for ovarian cancer has not yet
      been clearly established. In the present study, lower protein expression levels
      of SPARCL1 were detected in ovarian cancer tissues when compared with adjacent
      normal tissues. Overexpression of SPARCL1 significantly suppressed the
      proliferation and migration of cells from the ovarian cancer cell line SKOV-3,
      whereas knockdown of SPARCL1 significantly increased cell growth and migration.
      Furthermore, the results revealed that SPARCL1 overexpression significantly
      suppressed the activation of the mitogen-activated protein kinase kinase
      (MEK)/extracellular signal-related kinase (ERK) signaling pathway. Collectively,
      these results indicated that SPARCL1 may suppress the proliferation and migration
      of ovarian cancer cells by downregulating signaling via the MEK/ERK pathway.

PMID- 30233673
TI  - Regulatory role of microRNA-185 in the recovery process after ankle fracture.
AB  - The present study aimed to investigate the expression of microRNA (miR)-185 in
      the bone and blood tissues following ankle fracture, and its regulatory mechanism
      in the ankle fracture recovery process. In total, 28 patients with ankle
      fractures were included, including 15 cases receiving surgical treatment within 1
      7 days after fracture, and 13 cases receiving surgery within 8-14 days after
      fracture. Reverse transcription-quantitative polymerase chain reaction was
      performed to detect the mRNA expression levels. Western blot analysis and ELISA
      were used to determine the protein expression levels. Bioinformatics analysis and
      dual-luciferase reporter assay were applied to predict and confirm the upstream
      regulator of tumor growth factor (TGF)-beta1. An MTT assay was performed to
      assess the cell proliferation. Compared with the 1-7-day surgery group, the mRNA
      and protein expression levels of TGF-beta1 were significantly elevated, while the
      expression levels of miR-185 were significantly declined in the bone and blood
      tissues in the 8-14-day surgery group. Bioinformatics analysis and dual
      luciferase reporter assay predicted and confirmed that TGF-beta1 was the direct
      target gene of miR-185. Moreover, upregulated expression of miR-185 significantly
      decreased the protein expression levels of TGF-beta1 and reduced the
      proliferating activity of hFOB1.19 cells. Within two weeks after ankle fracture,
      the expression levels of TGF-beta1 are significantly upregulated in the bone and
      blood tissues, which may have been associated with the downregulated expression
      of miR-185. miR-185 may modulate TGF-beta1 to regulate the recovery of ankle
      fracture. These findings may contribute to the understanding of the biological
      functions and effects of miRNA-185 and TGF-beta1 in ankle fractures.

PMID- 30233675
TI  - Capsid protein Vp1 from chlamydiaphage phiCPG1 effectively alleviates
      cytotoxicity induced by Chlamydia trachomatis.
AB  - Chlamydia trachomatis is the leading cause of sexually transmitted bacterial
      infections. C. trachomatis genital infection may lead to pelvic inflammatory
      disease, ectopic pregnancy and tubal infertility, which are major public health
      problems. However, the pathogenic mechanisms of this bacterium remain unclear,
      and the efficacy of clinical therapeutics is unsatisfactory. In the current
      study, whether Vp1 can alleviate the cytotoxicity induced by Chlamydia
      trachomatis infection was investigated. C. trachomatis was pre-treated with BSA
      or purified Vp1 protein and used to infect HeLa cells. It was observed that Vp1
      significantly inhibited the infectivity of C. trachomatis in cell cultures. In
      addition, the Vp1 pretreatment reduced the chlamydial Hsp60 protein levels and
      decreased the C. trachomatis inclusion number. The Vp1 pretreatment also
      prevented C. trachomatis-induced cytotoxicity in host cells. Furthermore, the
      chlamydial suppression of host cell proapoptotic p53 protein and the induction of
      antiapoptotic cIAP-2 and Mcl-1 gene expression were reversed by the Vp1
      pretreatment. These observations suggest that Vp1 has a clear inhibitory effect
      on C. trachomatis growth in vitro.

PMID- 30233674
TI  - Cellular signaling pathways regulating beta-cell proliferation as a promising
      therapeutic target in the treatment of diabetes.
AB  - It is established that a decrease in beta-cell number and deficiency in the
      function of existing beta-cells contribute to type 1 and type 2 diabetes
      mellitus. Therefore, a major focus of current research is to identify novel
      methods of improving the number and function of beta-cells, so as to prevent
      and/or postpone the development of diabetes mellitus and potentially reverse
      diabetes mellitus. Based on prior knowledge of the above-mentioned causes,
      promising therapeutic approaches may include direct transplantation of islets,
      implantation and subsequent induced differentiation of progenitors/stem cells to
      beta-cells, replication of pre-existing beta-cells, or activation of endogenous
      beta-cell progenitors. More recently, with regards to cell replacement and
      regenerative treatment for diabetes patients, the identification of cellular
      signaling pathways with related genes or corresponding proteins involved in
      diabetes has become a topic of interest. However, the majority of pathways and
      molecules associated with beta-cells remain unresolved, and the specialized
      functions of known pathways remain unclear, particularly in humans. The current
      article has evaluated the progress of research on pivotal cellular signaling
      pathways involved with beta-cell proliferation and survival, and their validity
      for therapeutic adult beta-cell regeneration in diabetes. More efforts are
      required to elucidate the cellular events involved in human beta-cell
      proliferation in terms of the underlying mechanisms and functions.

PMID- 30233676
TI  - Combination of magnetic resonance imaging and targeted contrast agent for the
      diagnosis of myocardial infarction.
AB  - Myocardial infarction is one of the most common human cerebrovascular conditions
      and frequently leads to ischemic stroke. Evidence has indicated that magnetic
      resonance imaging (MRI) is a potential method for the diagnosis of patients with
      cardiovascular injury. However, the efficacy of MRI in diagnosing patients with
      myocardial infarction requires to be improved. In the present study, a novel nano
      size contrast agent, a chitosan/Fe3O4-enclosed albumin (CFEA), was introduced
      that was used to quantify blood volume and permeability in the infarcted
      myocardium. A total of 68 patients with suspected myocardial infarction were
      recruited to analyze the efficacy of MRI combined with CFEA (MRI-CFEA). All
      patients received diagnosis by MRI and MRI-CFEA. It was revealed that MRI-CFEA
      provided a higher signal intensity than MRI in the same patients. It was
      demonstrated that the diagnostic efficacy of MRI-CFEA for patients with
      myocardial infarction was higher than that of MRI (P<0.05). By MRI-CFEA, 50/68 of
      cases with myocardial infarction were diagnosed, providing a significantly higher
      diagnostic rate compared with the 38/68 of cases diagnosed by contrast-enhanced
      MRI (P<0.01). MRI-CFEA successfully discriminated the infarcted regions based on
      a decreased fractional blood volume and increased permeability-surface (PS) area
      product in the infarcted myocardium. A pharmacodynamics analysis indicated that
      CFEA was eliminated within 24 h in all individuals. In conclusion, the present
      study provided a novel method to diagnose infarcted myocardium for patients with
      myocardial infarction, providing an imaging biomarker for the assessment of
      endothelial dysfunction in the clinic.

PMID- 30233677
TI  - Long noncoding RNA TCONS_00024652 regulates vascular endothelial cell
      proliferation and angiogenesis via microRNA-21.
AB  - Acute coronary syndrome caused by the rupture of atherosclerotic plaques is one
      of the primary causes of major cardiovascular events, and neovascularization
      within the plaque is closely associated with its stability. Long noncoding RNA
      (lncRNAs) is a type of noncoding RNA that serves a crucial role in regulating
      vascular endothelial cells (VECs). The aim of the present study was to
      investigate the effect of lncRNA TCONS_00024652 on the proliferation and
      angiogenesis of VECs following stimulation with TNF-alpha. The expression of
      lncRNA and miRNA was measured in human umbilical vein endothelial cells (HUVECs)
      by reverse transcription-quantitative polymerase chain reaction. Cell
      proliferation was measured using a Cell Counting Kit-8 assay. Wound healing and
      tube formation assays were performed to determine cell migration and
      angiogenesis. Interactions between TCONS_00024652 and miR-21 were determined
      using bioinformatics and a dual-luciferase reporter assay. The results
      demonstrated that TCONS_00024652 is highly expressed in TNF-alpha-induced HUVECs.
      Functional assays demonstrated that the dysregulated expression of TCONS_00024652
      promotes endothelial cell proliferation and angiogenesis, whereas TCONS_00024652
      knockdown induces the opposite effects. Bioinformatics analysis using starBase
      predicted putative binding at the 3'-untranslated region of TCONS_00024652 and
      miR-21 and luciferase reporter assays further verified this interaction. The
      results of the present study suggest that the targeting of TCONS_00024652 by miR
      21 may be a potential method of improving vascular endothelial dysfunction,
      neovascularization maturation and plaque stabilization.

PMID- 30233678
TI  - Mixed lineage kinase-4 promotes gastric carcinoma tumorigenesis through
      suppression of the c-Jun N-terminal kinase signaling pathway.
AB  - Mixed lineage kinase-4 (MLK-4) is an important member of the mixed-lineage family
      of kinases that regulates the extracellular signal-regulated kinases and c-Jun N
      terminal kinase (JNK) signaling pathways. The functions and mechanisms of MLK-4
      in cancer initiation and progression have not been well understood. The present
      study investigated the expression, function and regulatory mechanism of MLK-4 in
      gastric carcinoma cells. Biochemical data indicated that normal MLK-4 was
      downregulated, which exerted dominant negative effects on gastric carcinoma cell
      viability, migration and invasion. The experimental data demonstrated that MLK-4
      supplement abrogated activity of these mutants and induced inhibitory effects on
      gastric carcinoma cell viabilty, migration and invasion in vitro and in vivo. In
      addition, to determine the regulatory mechanism of MLK-4, its signaling pathway
      was assessed in gastric carcinoma cancer cells by regulating MLK-4. The present
      observations indicated that restoring MLK-4 activity by supplemental MLK-4
      reduced gastric carcinoma cell colony formation in vitro and suppressed tumor
      viability, migration and invasion in vivo. The results of the present study
      indicated that MLK-4 may be a potential protein for targeting gastric carcinoma
      by suppressing kinases, which may lead to reduction of JNK signaling and enhance
      therapeutic efficacy in gastric carcinoma.

PMID- 30233679
TI  - Combined effects of Lenvatinib and iodine-131 on cell apoptosis in nasopharyngeal
      carcinoma through inducing endoplasmic reticulum stress.
AB  - Nasopharyngeal carcinoma (NPC) is a type of malignant tumor characterized by high
      invasiveness, metastatic potential and worldwide incidence among patients with
      head and neck cancer. It has previously been demonstrated that Lenvatinib (LEB)
      is an efficient anti-cancer agent by multi-targeting of tyrosine kinase
      inhibitors. Iodine-131 (I-131) therapy has been accepted for the treatment of
      thyroid cancer and other carcinomas. In the present study, the combined effects
      of LEB and I-131 were investigated on NPC and the potential signal pathway
      mediated by LEB and I-131 on NPC cells was explored. Inhibitory effects of LEB
      and I-131 for NPC cells growth were investigated via MTT assay. Migration and
      invasion of NPC cells was studied by aggression assays following incubation of
      LEB and I-131. Apoptosis of NPC cells and tissues were analyzed via flow
      cytometry and TUNEL assay, respectively. Apoptosis-related gene expression levels
      in NPC cells following treatment with LEB and I-131 were determined by western
      blotting. Endoplasmic reticulum (ER) stress in NPC cells were analyzed in NPC
      cells and tumor tissues. Immunohistochemistry was used to analyze the efficacy of
      LEB and I-131 in NPC-tumor bearing mice. The results demonstrated that combined
      treatment of LEB and I-131 significantly inhibited growth, apoptosis, migration
      and invasion of NPC cells compared with single agent therapy. Apoptosis-related
      gene expression levels of caspase-3 and caspase-9 were upregulated by LEB and I
      131, whereas B call lymphoma-2, and P53 were downregulated in NPC cells and tumor
      tissues. In addition, signal mechanism analysis demonstrated that combined
      treatment of LEB and I-131 promoted expression levels of activating transcription
      factor 6, inositol-requiring protein 1 (IER1), protein kinase RNA-like
      endoplasmic reticulum kinase (RERK), and C/EBP homologous protein in NPC cells.
      Furthermore, combined treatment of LEB and I-131 markedly inhibited in vivo
      growth of NPC and further prolonged survival of experimental mice compared with
      single agent and control groups. Immunohistochemistry indicated that c-jun N
      terminal kinase and Caspase-3 were increased in NPS tumor tissues in xenograft
      models treated with LEB and I-131. Apoptotic bodies were also increased in tumors
      treated by LEB and I-131. In conclusion, these findings indicate that combined
      treatment of LEB and I-131 may inhibit NPC growth and aggression through
      upregulation of ER stress, suggesting combined treatment of LEB and I-131 may be
      a potential therapeutic schedule for the treatment of NPC.

PMID- 30233681
TI  - Development and evaluation of LAMP, CPA and IMSA methods for rapid detection of
      the AML1/ETO fusion gene in acute myeloid leukemia.
AB  - The objective of the present study was to determine whether the loop-mediated
      isothermal amplification (LAMP), cross-priming amplification (CPA), and/or
      isothermal multiple-self-matching-initiated amplification (IMSA) methods can
      provide rapid detection of the runt related transcription factor 1/runt related
      transcription factor 1 translocation partner 1 (AML1/ETO) fusion gene in acute
      myeloid leukemia (AML). According to the sequence of the AML1/ETO fusion gene
      available in GenBank and the principles of the LAMP, CPA and IMSA methods,
      specific primers were designed to bind a conserved region of the AML1/ETO gene in
      each assay. Following optimization of the conditions for the LAMP, CPA and IMSA
      assays, the specificity and sensitivity of the assays were examined and compared.
      In addition, 41 clinical samples were assayed using the three methods. It was
      observed that a ladder-like pattern of DNA products was produced in AML1/ETO
      positive samples in all three assays, whereas no DNA product was generated with
      the controls. The detection limit of the LAMP and CPA assays was 50 copies/tube,
      and for the IMSA assay was 10 copies/tube. This sensitivity was consistent, and
      improved in the latter case, compared with that of the reverse transcription
      polymerase chain reaction (RT-PCR) assay. Furthermore, the detection rate for
      bone marrow or peripheral blood samples was 9.76%, and the agreement among the
      LAMP, CPA, IMSA and RT-PCR methods was 100%. Therefore, the LAMP, CPA and IMSA
      methods optimized in the present study provided rapid detection of the AML1/ETO
      fusion gene for an initial clinical diagnosis of AML. In addition, the LAMP, CPA
      and IMSA assays are straightforward to perform and do not require specialized
      instruments. Therefore, these three isothermal methods may be used to perform
      field tests or assays at resource-limited hospitals.

PMID- 30233680
TI  - Nrf2-dependent antioxidant response mediated the protective effect of tanshinone
      IIA on doxorubicin-induced cardiotoxicity.
AB  - Doxorubicin (DOX), a potent and widely used anticancer agent, can give rise to
      severe cardiotoxicity that limits its clinical use by inducing oxidative stress.
      Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the central regulator of
      cellular responses to electrophilic/oxidative stress, which serves a critical
      role in maintenance of normal cardiac function. Tanshinone IIA (Tan IIA) has
      previously been reported to protect against DOX-induced cardiotoxicity. The aim
      of the present study was to elucidate whether Nrf2 signaling serves a role in the
      underlying mechanism. In the animal model, DOX induced acute cardiotoxicity,
      whereas Tan IIA pretreatment reduced the activity of myocardial enzymes, and
      increased activity of the antioxidant enzymes superoxide dismutase, catalase and
      glutathione (GSH). Furthermore, Tan IIA pretreatment (3-10 uM) significantly
      increased the cell viability and markedly restored morphological changes in DOX
      injured H9c2 cells, decreased the generation of reactive oxygen species, and
      increased the level of intracellular GSH. Additionally, Tan IIA pretreatment also
      induced the nuclear accumulation of Nrf2 and its downstream genes heme oxygenase
      1, NAD(P)H dehydrogenase (quinone) 1, and glutamate-cysteine ligase catalytic
      subunit in both the mice cardiac tissues and H9c2 cells. Nrf2 knockdown by small
      interfering RNA downregulated Tan IIA-induced Nrf2 activation and reversed the
      effect of Tan IIA on the DOX-induced inhibition of cell viability. These results
      suggest that the Nrf2-dependent antioxidant response mediates the protective
      effect of Tan IIA on DOX-induced cardiotoxicity.

PMID- 30233682
TI  - Subarachnoid hemorrhage enhances the expression of TDP-43 in the brain of
      experimental rats and human subjects.
AB  - The transactive response DNA-binding protein of 43 (TDP-43) may be involved in
      neurodegenerative disease and in the response to brain injury; however,
      alterations in the expression of TDP-43 following subarachnoid hemorrhage (SAH)
      require further investigation. The present study reported a notable elevation in
      the expression of TDP-43 within the cerebrospinal fluid (CSF) of patients with
      aneurysmal SAH and increased brain expression of TDP-43 in a rat model of SAH.
      The TDP-43 protein and a derivative migrated at 43 and 24 kDa, respectively, as
      observed via the immunoblotting of concentrated CSF samples obtained from
      patients with SAH; no signal was detected in the CSF from healthy controls. SAH
      in rats was induced by intravascular suture puncture. The expression levels of
      TDP-43 in rat cortical lysates following SAH were increased at 0.5 h, peaked at
      48 h and remained significantly elevated at 72 h post-injury, compared with sham
      controls. TDP-43 immunolabeling indication localization within neurons,
      astrocytes and microglia in the experimental rats. Collectively, the findings of
      the present study indicated the early involvement of TDP-43 in the brain in
      response to SAH, and that expression levels of TDP-43 in the CSF may serve as a
      prognostic biomarker among patients with this condition.

PMID- 30233683
TI  - Silencing FOXC1 inhibits growth and migration of human oral squamous cell
      carcinoma cells.
AB  - Forkhead box C1 (FOXC1) is a transcription factor that serves an important role
      in regulating tumorigenesis and cancer progression. However, the expression and
      functional role of FOXC1 in oral squamous cell carcinoma (OSCC) remains unclear.
      FOXC1 protein expression was determined using immunohistochemical staining of
      OSCC tissues and normal tissues. Cell Counting Kit-8, colony formation, migration
      and 5-ethynyl-2'-deoxyuridine assays were performed to investigate the role and
      underlying mechanism of action of FOXC1 in OSCC. A consistent increase in the
      immunoreactive intensity of FOXC1 in OSCC tissues as compared with that in
      adjacent normal tissues was demonstrated. Knockdown of FOXC1 impaired cell growth
      and colony formation by inhibiting cell proliferation and reducing cyclin B1 and
      cyclin D1 levels in OSCC cells. FOXC1-silenced OSCC cells exhibited decreased
      migration compared with that demonstrated by the control cells, accompanied by a
      downregulation of matrix metalloproteinase (MMP)-2 and MMP-9. Collectively, the
      results of the present study demonstrated that FOXC1 functions as an oncogene in
      OSCC and may be an important therapeutic target and predictive biomarker for
      OSCC.

PMID- 30233684
TI  - Expression levels of IL-15 and IL-17 in synovial fluid of rheumatoid arthritis
      animal model.
AB  - The aim of the present study was to investigate the expression levels of
      interleukin-15 (IL-15) and interleukin-17 (IL-17) in synovial fluid of rheumatoid
      arthritis (RA) animal model, and to investigate their correlations with RA. A
      total of 100 Wistar rats were selected, among which 60 rats were used to
      establish the collagen II-induced arthritis (CIA) model as the model observation
      group, and the remaining 40 rats were used as blank control group. The levels of
      IL-15 and IL-17 in synovial fluid were detected via enzyme-linked immunosorbent
      assay (ELISA) at 1, 7, 14, 21 and 28 days after successful modeling. RA was
      evaluated by using arthritis index (AI) and pedal swelling volume. The expression
      levels of IL-15 and IL-17 in synovial fluid of rats in model observation group
      were higher than those in blank control group (P<0.05), and the levels of IL-15
      and IL-17 in model observation group were gradually increased over time. In model
      observation group at 7 days after modeling, AI and pedal swelling volume began to
      be increased gradually reaching a peak at 28 days. The pedal swelling volume of
      CIA model rats was significantly higher than that of the blank control group
      (P<0.05). The increased expression levels of IL-15 and IL-17 in synovial fluid of
      rats in the CIA model observation group are correlated with the activity of
      disease, which can be used as reference indexes for the activity of RA.

PMID- 30233685
TI  - Effects of tirofiban on stent thrombosis, Hs-CRP, IL-6 and sICAM-1 after PCI of
      acute myocardial infarction.
AB  - Effects of tirofiban on stent thrombosis, high-sensitivity C-reactive protein (Hs
      CRP), interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM
      1) after percutaneous coronary intervention (PCI) of acute myocardial infarction
      (AMI) were investigated. A total of 94 AMI patients receiving PCI in Shouguang
      City People's Hospital from January 2016 to September 2016 were selected and
      randomly divided into control (n=47) and observation group (n=47). The control
      group was treated with aspirin + clopidogrel before and after operation, while
      the observation group was treated with tirofiban based on the treatment of
      control group. The postoperative stent thrombosis was compared between the two
      groups, and the serum Hs-CRP, IL-6 and sICAM-1 levels before operation and at 24
      and 48 h after operation were also compared between two groups. Moreover, the
      incidence rates of adverse reactions in the groups were observed. Finally,
      patients were followed-up for 1 year to observe the total incidence rate of
      adverse cardiac events and life quality of patients in both groups. The
      thrombolysis in myocardial infarction flow grading in observation after treatment
      was significantly superior to that in control group (P<0.05). The levels of Hs
      CRP, IL-6 and sICAM-1 in both groups at 24 and 48 h after operation were
      significantly decreased compared with those before operation, and they were
      decreased more obviously in observation group (P<0.05); there were no significant
      differences in the incidence rates of adverse reactions between the groups
      (P>0.05). Besides, the 1-year follow-up showed that the total incidence rate of
      adverse cardiac events in observation was significantly lower than that in
      control group, and the life quality scores were obviously higher than those in
      control group (P<0.05). The treatment of AMI patients undergoing PCI with
      tirofiban can effectively prevent stent thrombosis, and alleviate the
      inflammatory response of patients, it is safe and reliable with important
      clinical significance.

PMID- 30233686
TI  - Analysis on the level of IL-6, IL-21, AMH in patients with auto-immunity
      premature ovarian failure and study of correlation.
AB  - Expression of interleukin-6 (IL-6), interleukin-21 (IL-21) and anti-mullerian
      hormone (AMH) in premature ovarian failure (POF) patients were observed to
      explore the correlation of each indicator and its significance in POF. One
      hundred and forty-two patients diagnosed with POF in Binzhou City Center Hospital
      from June 2014 to December 2015 were selected as the observation group. At the
      same time, another 140 healthy women were selected as the control group. The
      serum levels of IL-6, IL-2l, AMH, follicle stimulating hormone (FSH) and
      luteinizing hormone (LH), estradiol (E2), testosterone (T) and basal antral
      follicle count (AFC), and mean ovarian volume (MOV) were determined and compared;
      correlation analysis of IL-6, IL-2l and AMH with other indicators was performed.
      Compared to the control group, the serum levels of IL-6, IL-21, FSH and LH in the
      observation group were significantly higher (P<0.05), while E2, T, AMH levels in
      the serum, AFC and MOV were significantly lower (P<0.05). Spearman's correlation
      analysis showed that IL-6, IL-21 was positively correlated with FSH and LH
      (P<0.05), but negatively correlated with E2, T and MOV (P<0.05). AMH was
      negatively correlated with FSH and LH, but positively correlated with E2, T and
      MOV. Our results showed that the expression of IL-6, IL-21 and AMH were related
      to the occurrence and development of POF, IL-6, IL-21 and AMH can be used as the
      primary screening indexes for POF patients.

PMID- 30233687
TI  - miR-29b affects neurocyte apoptosis by targeting MCL-1 during cerebral
      ischemia/reperfusion injury.
AB  - The present study aimed to determine whether an miRNA (miR)-29b inhibitor
      protected against cerebral ischemia/reperfusion (I/R) injury in vitro and to
      investigate the underlying mechanisms. As a model for induced cerebral IR injury,
      N2a cells were exposed to an oxygen-glucose deprivation/reoxygenation (OGD/R)
      environment. Using this model, it was demonstrated that miR-29b was significantly
      upregulated compared with cells in a normal environment. The interactions between
      miR-29b and myeloid cell leukemia sequence (MCL)-1 were then investigated using
      dual-luciferase assays, revealing a strong regulation of MCL-1 through the
      3'untranslated region. Using the OGD/R model, the present study additionally
      examined the effects of miR-29b and miR-29b inhibitor on cell viability and
      apoptosis using Cell Counting kit 8 and flow cytometry assays, respectively. miR
      29b transfection led to increased N2a cell apoptosis and reduced cell viability
      under an OGD/R environment. However, this effect was reversed by the miR-29b
      inhibitor. Finally, the effects of miR-29b on the expression of several Wnt
      associating proteins were examined. It was observed that B cell lymphoma-2 was
      inhibited by miR-29b, as was MCL-1, whereas caspase-3 expression was promoted.
      The miR-29b inhibitor demonstrated the opposite effect. Overall, miR-29b promoted
      neurocyte apoptosis by targeting MCL-1 during cerebral I/R injury. The results of
      the present study suggest a potential novel therapeutic target for the treatment
      of ischemic stroke.

PMID- 30233688
TI  - Therapeutic effects of Salvia miltiorrhiza injection combined with telmisartan in
      patients with diabetic nephropathy by influencing collagen IV and fibronectin: A
      case-control study.
AB  - Involvement of collagen IV (ColIV) and fibronectin (FN) in the occurrence and
      development of diabetic nephropathy (DN) and the effects of telmisartan and
      Salvia miltiorrhiza injection in the treatment of the patients were investigated.
      Two hundred and fifty-eight patients with stage IV DN were selected as the case
      group, and another 110 normal healthy subjects were incorporated as the control
      group. Involved patients were subdivided into different groups according to
      different treatment therapies; patients in the telmisartan group (T group) were
      given oral telmisartan; patients in the Salvia miltiorrhiza injection +
      telmisartan (S + T group) were administered with Salvia miltiorrhiza injection
      combined with telmisartan treatment, and there was a group of patients who
      received no intervention as the placebo group. After intervention, levels of
      glycemic indexes and renal damage indexes indicated downwards trends both in the
      T group and the S + T group when compared to the placebo group; besides, levels
      in the S + T group were much lower than those in the T group (all P<0.05).
      Additionally, in comparison among the above three intervention groups,
      differences in the fasting blood glucose, 2 h post-prandial blood glucose,
      glycosylated hemoglobin, blood urea nitrogen, serum creatinine and urinary
      albumin excretion rate were significant after treatment (all P<0.05). Further,
      before intervention, both Co1IV and FN in the urine were increased in the case
      group compared to the control group (all P<0.05). After intervention, both levels
      were apparently decreased. There were remarkable differences of Co1IV and FN
      levels in the urine when compared among three different intervention groups after
      treatment (P<0.05). Increased ColIV and FN levels may be partially responsible
      for the development of DN. Salvia miltiorrhiza injection with telmisartan have
      beneficial synergistic effects for DN patients through attenuating the increase
      in ColIV and FN, reversing hyperglycemia state and postponing ultrastructure
      changes of glomerular basement membrane.

PMID- 30233689
TI  - Changes of TNF-alpha, PDGF and HA in nasal secretions and olfactory function of
      patients with chronic sinusitis before and after endoscopic sinus surgery.
AB  - This study aimed to investigate the changes of tumor necrosis factor-alpha (TNF
      alpha), platelet-derived factor (PDGF), hyaluronic acid (HA) in nasal secretions
      and olfactory function in patients with chronic sinusitis before and after
      endoscopic sinus surgery. A total of 94 patients with chronic sinusitis treated
      at Xiangyang No.1 People's Hospital, Hubei University of Medicine (Xiangyang,
      China) from May 2016 to April 2017 were randomly divided into the control and
      observation groups, with 47 patients in each group. The observation underwent
      endoscopic sinus surgery, while the control group were treated with traditional
      extranasal surgery. The treatment efficacy of the two groups were compared 3
      months after the treatment. A self-designed symptom questionnaire was used to
      evaluate the symptom scores. Enzyme-linked immunosorbent assay (ELISA) was used
      to detect the TNF-alpha, PDGF and HA levels in nasal secretions. The olfactory
      function of the patients was evaluated by the standard T&T olfactometry test. The
      life quality before and after the treatment was compared by using the SNOT-20
      questionnaire. The treatment efficacy of the observation group was significantly
      higher than that of the control group (P<0.05). Both groups showed improved
      symptom scores after the treatment, while improvement in the observation group
      was more obvious (P<0.05). The observation showed significantly lower TNF-alpha
      level than the control group (P<0.05). One, four and eight weeks after treatment,
      the levels of PDGF and HA were significantly higher in the observation group than
      in the control group (P<0.05). Both groups exhibited significantly improved
      olfactory function scores after treatment, and improvement in the observation
      group was more than that in the control group (P<0.05). After treatment,
      decreased scores of SNOT-20 in the observation group was more significant
      (P<0.05). Compared with traditional surgery, endoscopic surgery resulted in
      lighter postoperative inflammatory responses, better nasal mucosa repair, and
      more improved postoperative olfactory function.

PMID- 30233691
TI  - Evaluation of drug release from paclitaxel + hirudin-eluting balloons and the
      resulting vascular reactivity in healthy pigs.
AB  - This study explored drug release from paclitaxel + hirudin-eluting balloons in a
      healthy pig coronary artery model and objectively evaluated the vascular
      reactivity after balloon intervention. A total of 12 healthy white pigs were used
      for the analysis of drug release from the experimental balloon. The observational
      time-points included immediately following implantation and day 7, 30, and 180
      after surgery. At each time-point, two pigs were treated with the paclitaxel +
      hirudin-eluting balloon and one with the B. Braun paclitaxel-eluting balloon
      (control). Quantitative coronary angiography (QCA) of the target vessel was
      performed before and after balloon treatment. One pig died before the designated
      experimental endpoint, and no abnormal clinical signs or tissue lesions were
      observed in the other pigs. QCA showed different degrees of spasms after balloon
      treatment, all of which recovered shortly thereafter without intervention. The
      blood vessel lumens were all open and without dissection or angioma. Drug content
      determination showed that the experimental balloon performed better than the
      control balloon with regard to drug release, vascular absorption and expulsion
      rate. The paclitaxel + hirudin-eluting balloon catheter was easy to manipulate.
      The drug release from the experimental balloon was stable and resulted in good
      vascular reactivity. The safety and efficacy of the experimental balloon were not
      worse than the paclitaxel-eluting balloon that is currently on the market.

PMID- 30233690
TI  - Plasma miR-136 can be used to screen patients with knee osteoarthritis from
      healthy controls by targeting IL-17.
AB  - The current study mainly evaluated the plasma level of microRNA (miR)-136 in knee
      osteoarthritis (KOA) patients and determined if miR-136 could be used as a
      potential biomarker to screen KOA patients from healthy controls. It was
      demonstrated that plasma miR-136 was significantly decreased in the plasma of KOA
      patients. Moreover, the reduction in plasma miR-136 negatively correlated with
      the severity of KOA. Additionally, the increase in the serum interleukin (IL)-17
      level positively correlated with the severity of KOA. More importantly, dual
      luciferase assays and western blot assays indicated that IL-17 was a target gene
      of miR-136. Further analysis showed that plasma miR-136 could be used as a
      biomarker to screen KOA patients from healthy controls. In summary, for the first
      time, the present study revealed that through targeting IL-17, decreased plasma
      miR-136 levels could be used as a potential biomarker to screen KOA patients from
      healthy controls.

PMID- 30233692
TI  - Health risk behaviors among high school and university adolescent students.
AB  - Tobacco, alcohol and drug abuse constitute a public health concern. Data
      regarding health risk behaviors among Greek youth are scarce. The aim of the
      present study was to investigate health risk behaviors of a large adolescent
      sample (730 adolescents, 294 males and 436 females), residing in different areas
      of Greece, trace perceived side effects and associate the findings with the
      adopted lifestyle. High school students and University newcomers, aged 14-21
      years (17.8+/-4.5 years), self-reported health risk behaviors via an anonymous,
      closed-type, validated questionnaire. Simultaneous adoption of unhealthy habits,
      such as smoking and drug abuse, were not independent (chi2=38.668, P=0.01). Age
      was the most significant factor in the adoption of unhealthy behaviors; smoking
      (chi2=27.220, P=0.01), misuse of cannabis and recreational drugs (chi2=9.874,
      P=0.05) and combining alcohol and smoking with entertainment (chi2=8.708, P=0.05;
      chi2=317.309, P=0.05, respectively) were adopted more by the elder (18-20 years)
      than the younger (15-18 years) teenagers. Males were more prone to abuse of
      cannabis (chi2=8.844, P=0.01), whereas females combined drinking and smoking with
      loud music during entertainment (chi2=6.618, P=0.05). The majority (64%) reported
      driving after drinking alcohol and intense entertainment, especially in urban
      areas. Almost half of smokers (53.1%) and drug users (46.3%) first encountered
      smoking or drugs from friends. Educational institutions and entertainment venues
      were the main places of initiation of smoking (26%) or drug use (35.2%),
      respectively. Adolescents from touristic regions were more prone to smoking
      (33.9%, P=0.01) and drug abuse (53.7%, P=0.01). The lower the frequency of
      exercise, the higher the consumption of psychoactive substances (P=0.022). Youth
      engaging in unhealthy habits were also willing to use prohibited doping
      substances (56%, P=0.043). Health problems were the main reason to consider
      changing habits (72%). In conclusion, health risk behaviors were multifactorial
      and tended to cluster. Thus, preventive youth strategies should target negative
      peer influences, especially during late adolescence.

PMID- 30233693
TI  - Thymosin beta4 promotes glucose-impaired endothelial progenitor cell function via
      Akt/endothelial nitric oxide synthesis signaling pathway.
AB  - Circulating endothelial progenitor cells (EPCs) are a subtype of hematopoietic
      stem cells, which can differentiate into endothelial cells and restore
      endothelial function. However, high glucose decreases the number and impairs the
      function of EPCs. A previous study showed that thymosin beta4 (Tbeta4), a
      pleiotropic peptide beneficial for multiple functions of various types of cells,
      could promote EPC migration and dose-dependently upregulate the phosphorylation
      of Akt and endothelial nitric oxide synthesis signaling (eNOS). In present study,
      the hypothesis that Tbeta4 can improve glucose-suppressed EPC functions via the
      Akt/eNOS signaling pathway and restores the production of nitric oxide (NO) is
      investigated. EPCs were isolated from the peripheral blood of healthy volunteers
      and formed a cobblestone shape after 3-4 weeks of cultivation. Then, EPCs were
      treated with high concentrations of glucose (25 mM) for 4 days and administrated
      with Tbeta4 for further study. Transwell migration and tube formation assays were
      performed to access the migratory and angiogenic ability of EPCs. In addition,
      the quantity of Akt, eNOS and the concentration of nitric oxide (NO) was
      investigated. Functional studies showed that high concentrations of glucose
      significantly suppressed EPC function, while this adverse effect was reversed by
      the administration of Tbeta4. In addition, Akt small interfering (si)RNA and eNOS
      siRNA were demonstrated to reduce the protective effect of Tbeta4 against glucose
      impaired EPC functions. These findings suggest that Tbeta4 improves glucose
      impaired EPC functions via the Akt/eNOS signaling pathway.

PMID- 30233695
TI  - Guide sheath-assisted ureteroscope lithotripsy for upper ureteral calculi: An
      observational study on 81 cases.
AB  - The present study assessed the clinical efficacy of guide sheath-assisted
      ureteroscope lithotripsy in the treatment of upper ureteral calculi. A total of
      81 patients with upper ureteral calculi underwent ureteroscope lithotripsy
      assisted by a guide sheath between January 2012 and June 2014; of these, 63
      patients were successfully treated with simple rigid ureteroscope lithotripsy
      assisted by a ureteral access sheath, and 18 patients were successfully treated
      with rigid and flexible ureteroscope lithotripsy assisted by a guide sheath. At 1
      day after the surgery, ultrasound examination of kidneys, ureters and bladder,
      and urinary system computed tomography were used to re-check for residual stones,
      and 69 patients had stones with a diameter of <2 mm in the renal pelvis, while 12
      had stones of 2-4 mm in diameter. The operation time was 30-115 min (average,
      56.0+/-4.8 min); all patients underwent a successful surgical procedure. A total
      of 7 patients had an elevated temperature 37.4-39.1 degrees C (mean temperature,
      37.7+/-0.3 degrees C) after the surgery, but no other major complications were
      noted. After 1 month, the residual stones were completely discharged, so that the
      stone clearance rate was 100%. All patients were followed up for 3-12 months and
      no associated complications occurred. Overall, ureteroscope lithotripsy assisted
      by a guide sheath for the treatment of upper ureteral calculi had the benefit of
      water injection and reflux functions, as well as enhanced vision, reduced
      pressure within the renal pelvis, good discharge of stones as well as an improved
      efficiency and success rate compared with simple ureteroscopic lithotripsy.

PMID- 30233694
TI  - Claudin1 promotes the proliferation, invasion and migration of nasopharyngeal
      carcinoma cells by upregulating the expression and nuclear entry of beta-catenin.
AB  - The aim of the present study was to measure the expression of Claudin (CLDN) 1 in
      nasopharyngeal carcinoma (NPC) and to determine its biological function and
      mechanism of action. Reverse transcription-quantitative polymerase chain reaction
      and western blotting were performed to measure the expression of CLDN1 mRNA and
      protein, respectively, in the immortalized human nasopharyngeal epithelial cell
      line NP69 and NPC-TW01 cells. Subsequently, small interfering RNA against CLDN1
      and the LV-GFP-PURO-CLDN1 lentivirus were transfected into NPC-TW01 cells.
      Western blotting was used to determine the effects of CLDN1 down- and
      upregulation on the expression of the epithelial mesenchymal transition (EMT)
      markers E-cadherin and vimentin. In addition, the effect of CLDN1 on the
      expression of beta-Catenin was determined. The results demonstrated that levels
      of CLDN1 mRNA and protein in NPC cells were significantly higher than in NP69
      cells. Furthermore, the downregulation of CLDN1 inhibited the proliferation,
      invasion and migration of NPC-TW01 cells. The results of western blotting
      demonstrated that the downregulation of CLDN1 resulted in the upregulation of E
      cadherin and inhibition of vimentin in NPC-TW01 cells. By contrast, the
      overexpression of CLDN1 resulted in the downregulation of E-cadherin and
      upregulation of vimentin in NPC-TW01 cells. The downregulation of beta-catenin
      attenuated the cancer-promoting effect of CLDN1 on NPC-TW01 cells, whereas the
      upregulation of beta-catenin reversed the tumor-suppressing effect of CLDN1
      downregulation on NPC-TW01 cells. The results of the present study therefore
      demonstrate that CLDN1 expression is elevated in NPC cells. As an oncogene, CLDN1
      promotes the proliferation, invasion and migration of NPC cells by upregulating
      the expression and nuclear entry of beta-catenin.

PMID- 30233696
TI  - Eugenol protects the transplanted heart against ischemia/reperfusion injury in
      rats by inhibiting the inflammatory response and apoptosis.
AB  - The aim of the present study was to investigate the protective effect of eugenol
      on the transplanted heart and explore its mechanisms of action. Male Sprague
      Dawley rats were randomly divided into a sham group (n=10), a eugenol group (n=10
      pairs, donors and recipients) and a control group (n=10 pairs, donors and
      recipients). The recipients in the eugenol group received an intraperitoneal
      injection of eugenol (20 mg/kg/day). The sham group and the control group
      received equal volumes of physiological saline by intraperitoneal injection.
      After 15 days the recipients in the control and eugenol groups underwent
      abdominal heterotopic heart transplantation, while the sham group received only a
      coeliotomy. The orthotopic hearts in the sham group and the heterotopic hearts in
      the eugenol and control groups, as well as the peripheral blood samples from all
      three groups were taken 3 h post operation for biochemical, histopathological,
      molecular and apoptosis analyses. Compared with the control group, the eugenol
      treatment significantly reduced the myocardial malondialdehyde content, serum
      cardiac troponin I, creatine kinase-MB, tumor necresis factor-alpha and
      interleukin-6 levels (P<0.05) and significantly alleviated myocardial injury.
      Western blot analysis demonstrated that the protein expression of cleaved Poly
      (ADP-ribose) polymerase 1, BAX and active caspase-3 in the eugenol group were
      significantly decreased, while B-cell lymphoma 2 expression was significantly
      increased compared with the control group (P<0.05). The myocardial apoptosis rate
      of the eugenol group was significantly decreased compared with the control group
      (P<0.05). In conclusion eugenol treatment significantly reduced myocardial injury
      and demonstrated protective effects for the transplanted heart.

PMID- 30233697
TI  - AngII induces HepG2 cells to activate epithelial-mesenchymal transition.
AB  - The present study aimed to determine whether HepG2 can induce epithelial
      mesenchymal transition (EMT) via angiotensin II (AngII) simulation. The
      expression levels of EMT markers vimentin and E-cadherin in cancer tissues and
      adjacent tissues of patients with hepatocellular carcinoma (HCC) were detected by
      immunohistochemistry. In addition, HepG2 cells were stimulated with AngII, and
      the gene and protein expression levels of vimentin and E-cadherin were measured
      by reverse transcription-quantitative polymerase chain reaction and western blot
      analyses, respectively, whereas cell migration and invasion were assessed using
      Transwell assays. The AngII inhibitor Ang1-7 and the Ang1-7 inhibitor A779 were
      added to the system to further evaluate AngII-induced EMT. Compared with that in
      normal tissue, the expression level of vimentin in HCC tissue was increased,
      whereas that of E-cadherin was decreased. EMT occurred 48 h following AngII
      stimulation. The transcription level of E-cadherin in HepG2 cells was decreased,
      whereas that of vimentin was increased. In addition, the migration and invasion
      abilities of the cells were increased simultaneously. Ang1-7 partly inhibited
      AngII-induced EMT. When stimulated at an appropriate time, HepG2 cells have the
      ability to undergo EMT.

PMID- 30233698
TI  - Radial extracorporeal shock wave therapy promotes osteochondral regeneration of
      knee joints in rabbits.
AB  - Radial extracorporeal shock wave therapy (rESWT) has been proven to be effective
      for nonunion fractures. It was, thus, hypothesized that it may be used as a
      supplement therapy to promote osteochondral regeneration when combined with a
      scaffold previously prepared by our research group. In the present study, to
      verify this hypothesis, New Zealand white adult rabbits were anaesthetized and
      divided into three groups, as follows: Untreated control group, in which full
      thickness cylindrical osteochondral defects were created without repairing;
      scaffold group, in which rabbits were implanted with the scaffolds; scaffold plus
      rESWT group, in which rabbits were implanted with scaffolds and then treated with
      rESWT at 2 weeks post-surgery. At 6 and 12 weeks after surgery, the animals were
      sacrificed. Nitric oxide (NO) levels in the synovial cavity of the knee joints
      were measured by the Griess method. In addition, macroscopic observation and the
      gross score according to the International Cartilage Repair Society (ICRS)
      histological scoring system were determined. Histological evaluation was also
      performed by hematoxylin-eosin and Safranin O/fast green staining. The results
      demonstrated that both the scaffold and scaffold plus rESWT treatments
      significantly reduced NO levels in the synovial cavity at 6 weeks after surgery
      (P<0.05), whereas no significant difference was observed at 12 weeks after
      surgery. The ICRS scores of the scaffold and scaffold plus rESWT groups were
      significantly higher in comparison with those in the control group (P<0.05), and
      rESWT further increased these scores at 12 weeks after surgery (P<0.05).
      Histological results revealed that osteochondral regeneration was improved after
      treatment with scaffold or scaffold plus rESWT, with the latter displaying better
      results. These data suggested that rESWT improved the osteochondral regeneration
      when applied in combination with the scaffold, and that one of the underlying
      mechanisms may involve the reduction of NO in the synovial fluid. Therefore,
      rESWT may be a useful treatment for knee osteochondral regeneration.

PMID- 30233699
TI  - Sulbactam enhances the in vitro activity of sitafloxacin against extensively-drug
      resistant Acinetobacter baumannii.
AB  - The present study aimed to determine the in vitro activities of sulbactam and
      sitafloxacin against extensively-drug resistant Acinetobacter baumannii (XDR-A.
      baumannii). A total of 50 strains of XDR-A. baumannii were isolated from clinical
      specimens. Broth microdilution assay was applied to determine the minimum
      inhibitory concentration (MIC) for sulbactam and sitafloxacin. Microdilution
      checkerboard method was used to determine the in vitro activity of this
      antimicrobial combination. Accordingly, the fractional inhibitory concentration
      (FIC) and FIC index (FICI) were calculated. Time-kill study was also carried out
      for four strains with different susceptibilities to determine the bactericidal
      activities of individual or combined use of sitafloxacin and sulbactam. Isolates
      with MICs of sitafloxacin <=2 mg/l were considered to be susceptible to
      sitafloxacin. The susceptibility rate for sitafloxacin was 92% originally. When
      combined with sulbactam, this rate increased to 96%. Microdilution checkerboard
      results indicated that, when tested in combination, sulbactam/sitafloxacin
      exhibited marked synergistic and partial synergistic effects on 16 and 50% of the
      50 strains, respectively. Time-kill assay suggested that sulbactam enhanced the
      bactericidal activity of sitafloxacin and the combination induced a synergistic
      effect. For strains that were not susceptible to sitafloxacin, the bactericidal
      activities of the combination of sitafloxacin and sulbactam at a sub-MIC
      concentration were impaired. However, this impairment could be overcome with the
      increase of the concentration to 1X MIC. The present study demonstrated that
      sulbactam enhanced the in vitro antimicrobial activity of sitafloxacin against
      XDR-A. baumannii.

PMID- 30233700
TI  - Effects of different CYP2C19 genotypes on prognosis of patients complicated with
      atrial fibrillation taking clopidogrel after PCI.
AB  - The effects of different cytochrome P450 2C19 (CYP2C19) genotypes on the
      prognosis of clopidogrel resistance in patients complicated with atrial
      fibrillation taking clopidogrel after percutaneous coronary intervention (PCI)
      were investigated. Eighty patients who were complicated with atrial fibrillation
      and treated with clopidogrel antiplatelet therapy after PCI in Meizhou Hospital
      Affiliated to Zhongshan University from September 2015 to January 2017 were
      selected, and divided into two groups according to the CYP2C19 genotype:
      extensive metabolism (EM) group and poor metabolism (PM) group. The related risk
      factors of clopidogrel resistance were determined, and the platelet aggregation
      rate and clopidogrel resistance rate were compared between the two groups during
      treatment. Non-fatal myocardial infarction and serious life-threatening
      complications in the two groups were observed. The increased total cholesterol
      level and the history of smoking and drinking were the independent risk factors
      of atrial fibrillation after PCI. The platelet aggregation rates in the EM group
      at 1, 3 and 12 months after medication were significantly lower than those in the
      PM group in the same period (P<0.05). The clopidogrel resistance rates in EM
      group before medication and at 1, 3 and 12 months after medication were higher
      than those in PM group in the same period (P<0.05). The onset time of non-fatal
      myocardial infarction in EM group was earlier than that in PM group (P<0.05), the
      infarct area was larger than that in PM group (P<0.05), and the left ventricular
      ejection fraction (EF) after onset was lower than that in PM group (P<0.05). In
      conclusion, the increased total cholesterol level and the history of smoking and
      drinking are the independent risk factors of clopidogrel resistance in patients
      complicated with atrial fibrillation after PCI. The incidence rates of cardiac
      complications are increased significantly in patients with PM CYP2C19 genotype.

PMID- 30233701
TI  - Aconitine-induced cardiac arrhythmia in human induced pluripotent stem cell
      derived cardiomyocytes.
AB  - Pre-clinical evaluation of cardiac dysfunction is important for assessing the
      safety of traditional or novel medicines due to the universality of potential
      drug-induced heart failure and irreversible arrhythmia. Aconitine (ACO), a
      traditionally used anti-pyretic, analgesic and anti-rheumatic drug, has been
      reported to have arrhythmogenic effects. In the present study, the Real-Time
      Cellular Analysis Cardio system was applied to evaluate the arrhythmogenic
      effects of ACO in human induced pluripotent stem cell-derived cardiomyocytes
      (hiPSC-CMs). The results indicated that ACO is capable of increasing the
      frequency and decreasing the amplitude of hiPSC-CM contraction in a dose- and
      time-dependent manner. ACO at 0.25 uM increased the beating rate of hiPSC-CMs by
      3.7-fold within 30 min, while 3.0 uM of ACO increased the beating rate by 7.3
      fold. The present study also evaluated the potential pro-apoptotic effects of ACO
      by using caspase-3 and caspase-9 kits. To the best of our knowledge, the present
      study was the first to record the ACO-induced cardiac arrhythmia of hiPSC-CMsin
      real-time. The results also indicate that ACO-induced cell death is mediated, at
      least in part, by caspase-dependent apoptotic pathways.

PMID- 30233702
TI  - Naringin promotes cellular chemokine synthesis and potentiates mesenchymal
      stromal cell migration via the Ras signaling pathway.
AB  - Directional migration of mesenchymal stem cells (MSCs) is known to serve roles in
      bone fracture healing. Naringin is a traditional medicine used in China to treat
      bone injury and has been confirmed to act as a chemoattractant to MSCs. In the
      present study, the secretion of chemokines and stimulation of relevant signaling
      pathways by naringin were detected to determine the molecular mechanism of
      naringin-induced MSC migration. In these experiments, Quantibody(r) arrays were
      used to detect chemokines secreted by MSCs with or without the addition of
      naringin. The results revealed differential naringin-induced chemokine secretion
      of C-X-C motif chemokine (CXCL)5, CXCL6 and C-C motif chemokine 20. Furthermore,
      the Ras signaling pathway was markedly activated in the naringin-treated groups,
      suggesting that naringin may enhance the migrational ability of MSCs via Ras
      activation. Furthermore, naringin was able to promote the secretion of various
      chemokines derived from MSCs, which would, in turn, increase the mobility of
      MSCs. The aim of the present study was to provide novel candidate agents for
      clinical orthopedics and theoretical basis for the future improvement of
      adjunctive medication for bone fracture healing.

PMID- 30233703
TI  - Aerobic exercise-stimulated Klotho upregulation extends life span by attenuating
      the excess production of reactive oxygen species in the brain and kidney.
AB  - Aerobic exercise induces many adaptive changes in the whole body and improves
      metabolic characteristics. Klotho, an anti-aging gene, is mainly expressed in the
      brain and kidney. The roles of Klotho in the brain and kidney during aerobic
      exercise remain largely unknown. The present study aimed to determine whether
      aerobic exercise could influence the expression of Klotho, decrease reactive
      oxygen species (ROS) and prolong life span. Sprague Dawley rats were exercised on
      a motor treadmill. Klotho mRNA and protein expression levels in rat brain and
      kidney tissues were examined using reverse transcription-quantitative polymerase
      chain reaction and western blotting, respectively. ROS production was detected
      following intermittent aerobic exercise (IAE) or continuous aerobic exercise
      (CAE). Kaplan-Meier curve analysis demonstrated that aerobic exercise
      significantly improved rat survival (P<0.001). The ROS levels in rat brain and
      kidney tissues were decreased in the aerobic exercise groups compared with the
      control group (P<0.05). In addition, Klotho mRNA and protein expression levels
      were increased significantly following aerobic exercise compared with controls
      (P<0.05). There was no significant difference between the IAE and CAE groups in
      any experiments (P>0.05). These results suggest that aerobic exercise-stimulated
      Klotho upregulation extends the life span by attenuating the excess production of
      ROS in the brain and kidney. As Klotho exhibits a potential anti-aging effect,
      promoting Klotho expression through aerobic exercise may be a novel approach for
      the prevention and treatment of aging and aging-related diseases.

PMID- 30233704
TI  - USF1 promotes the development of knee osteoarthritis by activating the NF-kappaB
      signaling pathway.
AB  - The current study mainly aims to evaluate the expression pattern and underlying
      mechanism of upstream stimulating factor 1 (USF1) in the muscle tissues of knee
      osteoarthritis (KOA) patients. In accordance with previous findings, our data
      showed that muscle strength was significantly decreased in KOA patients compared
      with controls. Furthermore, several inflammatory factors, including tumor
      necrosis factor alpha (TNFalpha), IL-8, IL-6 and MCP-1, were associated with
      reduced muscle strength in KOA patients. Not surprisingly, NF-kappaB signaling
      was significantly activated in the muscle tissues of KOA patients compared with
      control individuals. Furthermore, we showed that USF1 was increased in the
      muscles of KOA patients compared with controls. More importantly, overexpression
      of USF1 in primary human skeletal muscle cells significantly increased the
      activation of NF-kappaB signaling as well as the levels of pro-inflammatory
      factors. In summary, we showed novel data that the upregulation of USF1 promoted
      NF-kappaB activation-induced inflammatory responses in muscle tissues of KOA
      patients.

PMID- 30233705
TI  - Retinoic acid receptor alpha expression exerts an anti-apoptosis effect on PC12
      cells following oxygen-glucose deprivation.
AB  - It has been established that the primary form of neuron death following hypoxic
      ischemic brain damage is apoptosis. Imbalances in the expression of genes in the
      B-cell lymphoma 2 (Bcl-2) family located in the mitochondrion, and in the
      expression of their encoded proteins, are key events in the mitochondrial
      apoptotic pathway, which lead to damage of cellular structure and function. The
      present study aimed to explore the regulatory effect of retinoic acid receptor
      alpha (RAR-alpha) on the apoptosis of PC12 cells induced by oxygen-glucose
      deprivation (OGD) in the retinoic acid signaling pathway. Recombinant adenovirus
      RAR-alpha small interfering RNA (Ad-siRAR-alpha) was used to transduce PC12
      cells, and the efficiency of RAR-alpha expression inhibition was detected by semi
      quantitative reverse transcription polymerase chain reaction (RT-PCR). An empty
      adenovirus vector was transfected in PC12 cells, which were used as the control.
      Flow cytometry with Annexin V-propidium iodide (PI) and fluorescence probe JC-1
      staining was used to detect the apoptosis rate and mitochondrial transmembrane
      potential (MMP), respectively, of PC12 cells after transduction with Ad-siRAR
      alpha. Furthermore, the expression levels of key genes in the RAR-alpha and
      mitochondrial apoptotic pathway, Bcl-2 and Bcl-2-associated protein (Bax) were
      analyzed by RT-quantitative (q)PCR and western blot analysis. RAR-alpha mRNA
      expression was observed to be decreased in PC12 cells following OGD-induced
      injury, and this decrease can be reversed by 4 umol/l ATRA treatment. After 36 h
      transfection with Ad-siRAR-alpha, RAR-alpha gene expression was significantly
      inhibited compared with the control (P<0.05). The results of Annexin V-PI,
      fluorescence probe JC-1 staining and flow cytometry demonstrated that the
      apoptosis rate significantly increased and MMP significantly decreased in OGD
      induced PC12 cells following transduction with Ad-siRAR-alpha compared with the
      control (both P<0.05). RT-qPCR and western blot analysis indicated that Bax
      expression was significantly increased and Bcl-2 expression was significantly
      decreased in PC12 cells transduced with Ad-siRAR-alpha after OGD-induced injury
      at the mRNA and protein level (P<0.05). In conclusion, Ad-siRAR-alpha
      transduction could promote apoptosis in OGD-induced PC12 cells. This suggests
      that the expression of Bax and Bcl-2 in the mitochondrial apoptosis signaling
      pathway is, at least in part, mediated by RAR-alpha expression, thereby
      indicating that RAR-alpha expression exerts an anti-apoptotic effect on OGD
      damaged PC12 cells.

PMID- 30233706
TI  - Association between the effect of controlled fluid resuscitation on massive
      hemorrhage and expression of human neutrophil lipocalin.
AB  - The present study was designed to investigate the association between the effect
      of controlled fluid resuscitation on massive hemorrhage and expression of human
      neutrophil lipocalin (HNL). A total of 112 patients confirmed with traumatic
      hemorrhage were enrolled as study subjects and were randomly divided into the
      control group (n=56) and observation group (n=56). The control group was treated
      with rapid fluid resuscitation, and the observation group was treated with
      controlled fluid resuscitation. The success rate of resuscitation, incidence rate
      of complications, and HNL levels were compared both before and after
      resuscitation at multiple time intervals. The success rate of resuscitation
      showed a significant improvement while the incidence rate of complications were
      decreased. The HNL levels in both groups revealed increase after resuscitation at
      3-10 h, thereby, they showed decline following peak point. However, the peak
      reduction in the observation group appeared earlier, while the HNL levels at 24
      and 72 h were significantly lower than those in the control group. The study
      concluded that the effect of controlled fluid resuscitation on massive hemorrhage
      was superior to that of rapid fluid resuscitation. Moreover, controlled fluid
      resuscitation was also able to decrease the level of HNL as well as inflammatory
      response.

PMID- 30233707
TI  - Expression and localization of nuclear factor erythroid 2-related factor 2 in the
      ovarian tissues of mice at different ages.
AB  - The aim of the present study was to investigate the expression and localization
      of nuclear factor erythroid 2-related factor 2 (Nrf2) in the ovaries of mice in
      different age groups, and to explore the association between Nrf2 and premature
      ovarian aging. The present study identified the localization of Nrf2 protein by
      performing immunohistochemical assay of ovarian tissues obtained from mice in
      different age groups. The mRNA expression levels of Nrf2 were detected via
      reverse transcription-quantitative polymerase chain reaction, while the
      expression levels of Nrf2 protein and apoptosis-associated proteins, including
      Caspase3 and B-cell lymphoma 2 (Bcl-2), were evaluated by western blot analysis.
      The results revealed that Nrf2 protein was mainly localized in granulosa cells,
      as well as in the secondary follicles and antral follicles of oocytes. Nrf2
      expression levels were significantly lower in mice aged 4 days compared with 12
      week-old mice (P<0.05), and the level of Nrf2 was lower in mice aged 40 weeks
      compared with those aged 12 weeks (P<0.05). In addition, the expression of the
      apoptosis protein Caspase3 in the ovarian tissue of mice aged 3, 8 and 12 weeks
      remained markedly greater when compared with those aged 4 days and 40 weeks. Bcl
      2, an anti-apoptotic protein, was also significantly expressed in the ovarian
      tissues of juvenile (4-day-old) mice when compared with mice aged >40 weeks
      (P<0.05). In conclusion, Nrf2 was highly expressed in the ovarian tissues of mice
      of childbearing age (8-12 weeks old) and may possibly be involved in ovarian
      regulatory functions. The results indicated that Nrf2 expression and localization
      may have important implications in the prevention of ovarian aging.

PMID- 30233708
TI  - Therapeutic effects of new-type hydraulic delivery vertebroplasty, balloon
      kyphoplasty and conventional pusher-type vertebroplasty on single segmental
      osteoporotic vertebral compression fracture.
AB  - This study aims to evaluate safety and practicality in clinical application for
      better guidance of single segmental osteoporotic vertebral compression fractures
      treatment. From May 2012 to September 2013, a total of 188 cases of patients with
      fractures, who received different treatment, were incorporated in the study and
      then divided into: group A (n=59), conventional pusher-type vertebroplasty; group
      B (n=54), balloon kyphoplasty; group C (n=60), new-type hydraulic delivery
      vertebroplasty treatment. The overall follow-up rate was 92.02%. Postoperative
      visual analogue scale (VAS) and Oswestry disability index (ODI) scores were
      significantly improved more than those of the preoperative scores in the three
      groups. Bone cement injection volumes in group A were significantly lower than
      those in group B and group C. Vertebral height recovery rates among groups were
      obviously different, showing statistical significance. After a year of follow-up,
      the vertebral height recovery outcome in group A was obviously poorer than that
      in group B and group C. A poorer outcome in group B was also found when compared
      with group C. In addition, the vertebral height restoration had a certain degree
      of loss, with the loss rate of 20.5, 14.0 and 7.5% in the three groups,
      respectively. Three operation methods have equivalent effects in the improvement
      of symptoms and functional recovery. Therefore, the new-type hydraulic delivery
      vertebroplasty provides a relatively more concise operation and shorter operation
      time, displaying more outstanding performance of clinical efficacy in spinal
      reconstruction and reduction of complications risks by evaluating the diffusion
      of the bone cement, vertebral height restoration rate and postoperative
      complications.

PMID- 30233709
TI  - Downregulated caveolin-1 expression serves a potential role in coronary artery
      spasm by inducing nitric oxide production in vitro.
AB  - The present study aimed to investigate the effects of downregulated caveolin-1
      (Cav-1) expression on nitric oxide (NO) production in lipopolysaccharide (LPS)
      damaged primary human umbilical vein endothelial cells (HUVECs) in a model of
      coronary artery spasm (CAS) microenvironment induced by acetylcholine (ACh)
      treatment. Small interfering RNA (siRNA)-mediated Cav-1 downregulation in HUVECs
      was confirmed by western blotting. The cell viability and superoxide dismutase
      (SOD) inhibition in HUVECs incubated with LPS (0, 10, 25, 50, 75 and 100 ug/ml)
      were measured by cell counting kit-8 assay and a SOD kit, respectively.
      Intracellular Ca2+ [(Ca2+)i] in Fluo4-acetoxymethyl ester-loaded cells was
      detected by fluorescence microscopy. NO levels in the cell culture supernatants
      were measured by the nitrate reductase method. The results indicated that
      transfection with Cav-1 siRNA, in particular siCav-1 (2), downregulated the Cav-1
      protein expression. LPS at a dose of 75 ug/ml induced a significant decrease in
      HUVECs/si-NC and HUVECs/siCav-1 viability compared with the other concentrations
      of LPS. Compared with the effects of untreated cells, SOD inhibition in HUVECs/si
      NC and HUVECs/siCav-1 was significantly decreased by LPS (75 ug/ml). In addition,
      ACh stimulation caused a greater increase in [Ca2+]i in HUVECs/si-NC as compared
      with LPS-treated HUVECs/si-NC. ACh stimulation also induced significantly higher
      NO levels in LPS-treated HUVECs/siCav-1 compared with LPS-treated HUVECs/si-NC
      cells (P<0.05). In conclusion, the downregulated Cav-1 expression served a key
      role in NO production in the in vitro model of CAS induced by ACh stimulation of
      LPS-damaged HUVECs.

PMID- 30233710
TI  - Effects of atrial fibrillation on complications and prognosis of patients
      receiving emergency PCI after acute myocardial infarction.
AB  - The effects of atrial fibrillation on complications and prognosis of patients
      receiving emergency percutaneous coronary intervention after acute myocardial
      infarction (AMI) were investigated. Eighty AMI patients treated with
      interventional vascular recanalization in the Affiliated Hospital of Weifang
      Medical University (Weifang, China) from July 2015 to October 2016 were selected,
      including 40 patients complicated with atrial fibrillation before operation
      (control group) and 40 patients without atrial fibrillation before operation
      (observation group). The systolic blood pressure, diastolic blood pressure, heart
      rate, arrhythmia and common complications after MI were compared. Changes in the
      coronary artery thrombolysis in myocardial infarction (TIMI) flow grade and left
      ventricular ejection fraction (LVEF) of patients were also recorded. Moreover,
      changes in brain natriuretic peptide (BNP) levels were compared. The recovery
      time of myocardial enzyme and total troponin in both groups was recorded. The
      systolic and diastolic blood pressure in the observation group were significantly
      higher than those in the control group (p<0.05). During the intervention, the
      total proportion of patients with ventricular arrhythmia, atrial arrhythmia,
      atrioventricular block and sinus tachycardia in the observation group was
      significantly lower than that in the control group (p<0.05). The total proportion
      of common complications after MI in the observation group was obviously lower
      than that in the control group (p<0.05). Coronary artery TIMI flow grades and
      LVEFs in the observation group were obviously higher than those in the control
      group. BNP levels in the observation group were significantly lower than those in
      the control group. The recovery time of myocardial enzyme and total troponin in
      the observation group was significantly earlier than that in the control group.
      Atrial fibrillation has a certain negative effect on the circulatory function in
      patients with AMI after the interventional therapy, and the proportions of
      arrhythmia and complications in patients after MI are increased at the same time,
      so the postoperative recovery of patients is slow with many complications.

PMID- 30233711
TI  - Effects of captopril and valsartan on ventricular remodeling and inflammatory
      cytokines after interventional therapy for AMI.
AB  - The effects of captopril and valsartan on ventricular remodeling and inflammatory
      cytokines after interventional therapy for acute myocardial infarction (AMI) were
      investigated. A total of 94 patients with AMI admitted to Honggang Hospital of
      Dongying from July 2016 to June 2017 were selected as study subjects. The
      patients were treated with interventional therapy and randomly divided into the
      observation group (n=47) and the control group (n=47). The control group received
      aspirin after operation, while the observation group received captopril and
      valsartan after operation. Three-dimensional ultrasonography was performed to
      evaluate ventricular remodeling. The related parameters included left ventricular
      end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left
      ventricular ejection fraction (LVEF), end-systolic sphericity index/end-diastolic
      sphericity index (ESSI/EDSI), systolic dyssynchrony index (SDI), diastolic
      dyssynchrony index (DDI), dispersion end systole (DISPES), DDI-late and DISPED
      late. The levels of inflammatory cytokines were determined by enzyme-linked
      immunosorbent assay (ELISA). The incidence of adverse reactions after treatment
      was compared. After treatment, LVEF in the control group was significantly lower
      than that in the observation group, while LVEDV, LVESV and the ratio of early
      diastolic (E) and late diastolic (A) (E/A) in the control group were
      significantly higher than those in the observation group (p<0.05). EDSI, DDI-late
      and DISPED-late in the control group were significantly higher than those in the
      observation group (p<0.05). ESSI, SDI and DISPES in the control group were
      significantly higher than those in the observation group (p<0.05). The levels of
      interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and tumor
      necrosis factor-alpha (TNF-alpha) in the observation group were significantly
      lower than those in the control group at 1, 4 and 8 weeks after treatment
      (p<0.05). The administration of captopril and valsartan after interventional
      therapy for AMI can effectively improve the cardiac function of patients, improve
      the synchronism of left ventricular diastole and contraction, and reduce the
      level of inflammation. It is safe and reliable, and has important clinical
      significance.

PMID- 30233712
TI  - Regulatory effect of immunosuppressive agents in mice with renal ischemia
      reperfusion injury.
AB  - This study was designed to investigate the regulatory effect of rapamycin in mice
      with renal ischemia-reperfusion injury. A total of 100 mice were randomly divided
      into normal control, sham operation, model and experimental groups with 25 rats
      in each group. Mice in the experimental group were subjected to rapamycin gavage.
      Mice in each group were sacrificed 24 h after operation. Then, blood, spleen and
      left kidney were collected. PAS staining was used for semi-quantitative analysis
      of renal pathological injury. Serum creatinine (SCr) and blood urea nitrogen
      (BUN) levels were measured. TUNEL method was used to detect cell apoptosis. Flow
      cytometry was used to detect the percentage of NKT cells. The expression of CXC
      chemokine ligand 10 (CXCL10), hypoxia-inducible factor-1alpha (HIF-1alpha) and
      vascular endothelial growth factor (VEGF) mRNA were detected by RT-qPCR. Semi
      quantitative scoring of renal pathological injury showed that pathological injury
      score of the experimental group was significantly lower than that of the model
      group (p<0.05). Serum levels of SCr and BUN in the experimental group was
      compared to those in the model group (p<0.05). The number of apoptotic cells in
      the experimental group was compared to that of the model group (p<0.05). The
      percentage of NKT cells in the experimental group was compared to that of the
      model group (p<0.05). The percentage of NKT cells was significantly higher in the
      kidney and peripheral blood of the experimental group than that in the model
      group (p<0.05). The expression levels of HIF-1alpha and VEGF mRNA in the model
      and experimental groups were significantly lower in the experimental group than
      those in the model group (p<0.05). The expression levels of CXCL10 mRNA in the
      model and experimental groups were significantly higher in the experimental group
      than those in the model group (p<0.05). The results indicated that rapamycin can
      significantly upregulate the expression level of CXCL9 and promote the
      accumulation of NKT cells in kidney from spleen through peripheral blood.
      Rapamycin can also inhibit the HIF-1alpha expression level and protect renal
      ischemia-reperfusion injury.

PMID- 30233713
TI  - De novo unbalanced translocation t(15;22)(q26.2;q12) with velo-cardio-facial
      syndrome: A case report and review of the literature.
AB  - The present study reports the case of a 3-h old male with a de novo unbalanced
      t(15;22) translocation and velo-cardio-facial syndrome (VCFS), with other
      abnormalities. The manifestations of the condition observed in the patient
      included cleft palate with feeding difficulties, respiratory infection,
      dysmorphic face with almond-shaped eyes, a long and wide nose, small and low-set
      ears, tetralogy of Fallot, cryptorchidism and varus equinus. Standard lymphocyte
      cytogenetic analysis using G-banding demonstrated a 45,XY,-22,der
      (15),t(15;22)(q26.2;q12) karyotype. Fluorescent in situ hybridization with
      DiGeorge/VCFS TUPLE 1 confirmed 22q11 deletions. These cytogenetic aspects appear
      to be rare in the etiology of VCFS, as >1% of all 22q11 deletions are the result
      of an unbalanced translocation, which involves chromosomes 22 and another
      chromosome. To the best of our knowledge, this is the second reported case where
      the clinical features associated with VCFS are combined with an unbalanced
      (15;22) translocation involving the critical 22q11.2 region.

PMID- 30233714
TI  - The influence of dexmedetomidine on remifentanil-induced hyperalgesia and the sex
      differences.
AB  - In the clinical settings, patients often develop opioid-induced hyperalgesia
      (OIH) after utilization of high dose intra-operative remifentanil. Systemic
      alpha2 agonists, including dexmedetomidine, are believed to reduce pain and
      opioid requirements after surgery, thus decreasing the incidence of hyperalgesia.
      The present study aimed to investigate the effect of dexmedetomidine on
      remifentanil-induced hyperalgesia and explored the sex differences. A total of 48
      patients (24 male, 24 female) with an American Society of Anesthesiologists
      physical status of I-II that were undergoing thyroidectomy were randomly assigned
      to one of the following six groups: Male controlled group (MC) and female
      controlled group (FC) (group MC, n=8 and group FC, n=8), which received a
      preoperative placebo of 0.2 ug.kg-1 normal saline and intraoperative remifentanil
      0.2 ug.kg-1.min-1; male and female group with low-dose dexmedetomidine (group
      MD1, n=8 and group FD1, n=8), which received preoperative dexmedetomidine 0.2
      ug.kg-1 and intraoperative remifentanil 0.2 ug.kg-1.min-1; and male and female
      groups with high-dose dexmedetomidine (group MD2, n=8 and group FD2, n=8), which
      received dexmedetomidine 0.6 ug.kg-1 and intraoperative remifentanil 0.2 ug.kg
      1.min-1. Result indicated that the visual analog scale (VAS) scores and morphine
      dosing frequency were significantly higher in MC and FC groups compared with the
      other same sex groups. Furthermore, the mechanical hyperalgesia threshold and
      patients' analgesia satisfaction score after surgery were significantly lower in
      MC and FC groups. Notably, the frequency of post-operative chills, nausea and
      vomiting were significantly lower in groups MD1, MD2, FD1 and FD2. The present
      findings indicated that low- and high-dose dexmedetomidine injection
      significantly decreased the patient's risk of enhanced pain intensity and
      increased postoperative morphine dosing caused by remifentanil-induced
      hyperalgesia. These findings suggest that the influence of dexmedetomidine
      displayed minimal significant differences between sex. Trial registration no.,
      IRB2018-YX-001 (Name of registry: Institutional Medical Ethics Committee of
      Tianjin Medical University General Hospital; date of registration: February 1,
      2016).

PMID- 30233715
TI  - Resolvin D1 inhibits the proliferation of lipopolysaccharide-treated HepG2
      hepatoblastoma and PLC/PRF/5 hepatocellular carcinoma cells by targeting the MAPK
      pathway.
AB  - Hepatocellular carcinoma (HCC) and hepatoblastoma are common malignant tumor
      types in China. The aim of the present study was to evaluate the effects of
      resolvin D1 (RvD1) on inflammatory factor levels and mitogen-activated protein
      kinase (MAPK) signaling in lipopolysaccharide (LPS)-treated liver cancer cells.
      First, HepG2 hepatoblastoma and PLC/PRF/5 HCC cells were cultured and treated
      with LPS with or without various concentrations of RvD1 (0, 0.025, 0.05, 0.1 and
      0.2%). Subsequently, ELISA was performed to measure the protein levels of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in the culture
      medium. In addition, cell proliferation of the liver cancer cells was assessed by
      MTT assay. Reverse transcription-quantitative polymerase chain reaction and
      western blotting were performed to detect the expression of TNF-alpha, IL-1beta
      and IL-6 in the cultured cells. Western blotting was also performed to assess the
      protein expression of phosphorylated extracellular signal-related kinase (p-ERK),
      p-c-Jun N-terminal kinase (p-JNK) and p-p38. Compared with the control group, LPS
      treatment increased the protein levels of TNF-alpha, IL-1beta and IL-6 in the
      culture medium, and RvD1 inhibited this increase in a concentration-dependent
      manner. RvD1 also reduced the LPS-induced increase in TNF-alpha, IL-1beta, IL-6,
      p-ERK, p-JNK and p-p38 expression levels in liver cancer cells. LPS promoted the
      proliferation of liver cancer cells, while RvD1 attenuated this effect. In
      summary, the current findings suggest that RvD1 inhibits cell proliferation and
      the expression of inflammatory cytokines in LPS-treated liver cancer cells by
      targeting the MAPK pathway.

PMID- 30233716
TI  - MicroRNA-744 promotes cell apoptosis via targeting B cell lymphoma-2 in gastric
      cancer cell line SGC-7901.
AB  - Gastric cancer (GC) affects the health of 1,000,000 people per year worldwide;
      however, the biological basis of GC remains largely unknown. The current study
      aimed to investigate the aberrant expression of miR-744 in GC for the effective
      treatment of patients with GC. Tumor and adjacent tissues were obtained from 30
      patients who underwent tumor resection surgery at Dongying People's Hospital. The
      results of reverse transcription-quantitative polymerase chain reaction indicated
      that the expression of miR-744 was significantly decreased in tumor tissues
      compared with the levels in adjacent tissues. Human gastric cancer cell line SGC
      7901 was then randomly divided into three different groups, including the
      control, miR-negative control (NC) and miR-744 mimic groups. A Cell Counting Kit
      8 assay demonstrated that there was a significant decrease in the proliferation
      rate of SGC-7901 cells in the miR-744 mimics group compared with that observed in
      the control and miR-NC mimics groups. In addition, flow cytometry demonstrated
      that apoptosis was significantly increased in the miR-744 mimics group compared
      with that observed in the control and miR-NC mimics groups. Western blotting
      indicated that the expression of B cell lymphoma 2 (Bcl-2), B cell lymphoma-2
      associated X protein and caspase-3 protein was significantly increased, while the
      expression of Bcl-2 was significantly decreased in the miR-744 mimics group
      compared with the levels observed in the control and miR-NC mimics groups. A dual
      luciferase assay verified that miR-744 directly targeted the 3'-untranslated
      region of Bcl-2. Taken together, the present study suggested that miR-744 serves
      a tumor suppressive role in GC by targeting Bcl-2.

PMID- 30233717
TI  - Percutaneous kyphoplasty treatment evaluation for patients with Kummell disease
      based on a two-year follow-up.
AB  - Percutaneous kyphoplasty (PKP) has been used in Kummell disease treatment for
      years. The objective of the current study was to evaluate the efficacy and safety
      of PKP in the treatment of patients with Kummell disease and to explore the
      association between cement injection volume and pain relief. A total of 50
      patients were enrolled in the present study and follow-up was 2 years. Efficacy
      was evaluated using the Visual Analog Scale (VAS), the Oswestry Disability Index
      (ODI) and the kyphotic angle (Cobb's angle). VAS and ODI were determined at the
      initial evaluation (prior to surgery), at 3 days, 3 months, and 1 and 2 years
      post surgery. Cobb's angle was measured prior to and 3 months, 1 year and 2 years
      following surgery. PKP safety was assessed by evaluating complications, including
      cement leakage and spinal cord compression. In the follow-ups, VAS significantly
      decreased from 7.00+/-0.78 pre-PKP to 3.14+/-0.67 at 2 years post-PKP (P<0.05).
      ODI significantly decreased from 73.88+/-8.60 prior to surgery to 22.84+/-8.85 at
      1 year following surgery (P<0.05) and did not significantly change at the
      following 2-year measurement (26.44+/-8.63). The Cobb's angle, measured at
      17.73+/-2.43 degrees  preoperatively, significantly decreased to 8.32+/-2.21
      degrees  at 3 months following surgery (P<0.05). On subsequent follow-ups at 1
      and 2 years, the Cobb's angle increased to 9.55+/-2.82 and 10.27+/-3.22 degrees ,
      respectively. A total of 8 patients exhibited signs of cement leakage during the
      PKP procedure. No patients experienced severe neurological deficits or
      complications. Spearman analysis demonstrated a positive correlation between
      cement injection volume and pain relief. The current study indicated that PKP was
      a safe and effective treatment for patients with Kummell disease and that there
      was a positive correlation between cement injection volume and pain relief. The
      current study may be used a reference in cement dosing for the treatment of PKP.

PMID- 30233718
TI  - Reduced peripheral blood miR-140 may be a biomarker for acute lung injury by
      targeting Toll-like receptor 4 (TLR4).
AB  - Acute lung injury (ALI) is a common complication of sepsis to which patients
      often succumb due to poor effective pharmacological interventions. Recent studies
      have focused on the potential application of circulating microRNAs (miRs or
      miRNAs) as novel prognostic and therapeutic biomarkers. The present study focuses
      mainly on miR-140, the role of which is poorly understood in the progression of
      ALI. The results of the present study revealed that toll-like receptor 4 (TLR4)
      expression was upregulated the lungs of rats with ALI. Meanwhile, serum levels of
      tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1beta were significantly
      increased in rats with ALI compared with normal control rats. These data
      indicated the successful establishment of LPS-induced ALI. Furthermore, miR-140
      was decreased in the peripheral blood of patients with ALI compared with control
      subjects. Receiver operator characteristic analysis indicated that miR-140 could
      be used to screen ALI patients and distinguish them from healthy controls. MiR
      140 was demonstrated to be downregulated in the plasma and lungs of rats with ALI
      compared with the normal control group. A dual luciferase reporter assay
      indicated that TLR4 was a target gene of miR-140. To investigate whether miR-140
      exerted its role via TLR4, a specific TLR4-targeting small interfering RNA was
      selected. It was revealed that TLR4 silencing was able to suppress the
      phosphorylation of NF-kappaB even in cells transfected with miR-140 inhibitor. In
      summary, reduced miR-140 expression and increased TLR4 signaling activation may
      serve a key role in the progression of ALI.

PMID- 30233719
TI  - Reduced expression of microRNA-199a-3p is associated with vascular endothelial
      cell injury induced by type 2 diabetes mellitus.
AB  - The aim of the present study was to investigate the function and mechanism of
      action of microRNA (miRNA or miR)-199a-3p in vascular endothelial cell injury
      induced by type 2 diabetes mellitus (T2DM). A total of 36 patients with T2DM (26
      males and 10 females; mean age, 52.5+/-7.0 years) and 20 healthy subjects (10
      males and 10 females; mean age, 55.6+/-4.5 years) were included in the present
      study. Peripheral blood samples were obtained from all participants and total RNA
      was extracted Reverse transcription-quantitative polymerase chain reaction was
      performed to determine the expression of miR-199a-3p. Following the transfection
      of human umbilical vein endothelial cells (HUVECs) with a negative control (NC)
      miRNA or miR-199a-3p mimics, cell proliferation was assessed using a Cell
      Counting kit-8 assay. Cell migration was investigated using Transwell assays and
      flow cytometry was performed to detect the apoptosis of HUVECs. HUVECs were
      infected with Ad-GFP-LC3B and laser-scanning confocal microscopy was performed to
      observe autophagosomes in HUVECs. Western blotting was used to measure the
      expression of proteins associated with autophagy and the phosphatidylinositol 3
      kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)-kappaB signaling
      pathway. MiR-199a-3p was downregulated in peripheral blood from patients with
      T2DM compared with healthy subjects. Transfection with miR-199a-3p mimics
      promoted the proliferation and migration of HUVECs. However, miR-199a-3p
      overexpression inhibited the apoptosis of HUVECs. MiR-199a-3p facilitated HUVEC
      autophagy by affecting autophagy-associated signaling pathways. Furthermore, miR
      199a-3p regulated the biological functions of HUVECs via the PI3K/AKT/NF-kappaB
      signaling pathway. The results of the present study suggest that miR-199a-3p
      expression was reduced in patients with T2DM compared with healthy subjects and
      may be associated with vascular endothelial cell injury. In addition, miR-199a-3p
      promoted the proliferation, migration and autophagy of HUVECs, potentially by
      regulating the PI3K/AKT/NF-kappaB signaling pathway. Therefore, miR-199a-3p may
      function as protector of vascular endothelia.

PMID- 30233720
TI  - Protective role of propofol in endometriosis and its mechanism.
AB  - Endometriosis (EM) is a common benign gynecological disorder. The present study
      aimed to investigate the potential role of propofol, a commonly used intravenous
      anesthetic agent, in the pathogenesis of EM. The EM cell line CRL-7566 was used
      in the present study. CRL-7566 cells were first treated with various
      concentrations of propofol (0, 1, 5 or 10 ug/ml) for specific duration, and the
      cell viability and apoptotic rate were determined by performing an MTT and a flow
      cytometric cell apoptosis assay, respectively. The protein and mRNA levels of
      cell proliferation- and apoptosis-associated genes were detected by western blot
      and reverse-transcription quantitative polymerase chain reaction, respectively.
      The results demonstrated that propofol inhibited CRL-7566 cell proliferation in a
      dose- and time-dependent manner. CRL-7566 cell apoptosis was dose-dependently
      induced by propofol treatment. In addition, propofol treatment significantly
      increased the levels of forkhead box (FOX)O1, FOXO3, Bim, pro-caspase-3, active
      caspase-3, p53 and p21. In conclusion, the present study suggested that propofol
      inhibited the proliferation and induced apoptosis of EM cells via inducing the
      expression/activation of multiple associated genes/proteins, indicating a
      protective role of propofol in EM.

PMID- 30233721
TI  - Evaluation of the potential of chicoric acid as a natural food antioxidant.
AB  - Dietary fat is important for human health, while its excessive consumption or the
      oxidation of lipids may cause various diseases. In the present study, the
      potential of chicoric acid (CA) as a natural food antioxidant was evaluated. To
      evaluate this, spectrophotometry analysis measured CA antioxidant activity, the
      analytical method of the sanitary standard of edible lard and rapeseed oil
      measured CA anti-oil oxidation, the Oxford cup method measured CA anti-microbial
      activity, Oil red O staining assessed intracellular triglycerides following CA
      administration, and RT-qPCR analysis and ELISA assessed CA anti-inflammatory
      activity. The results indicated that CA had a marked scavenging capacity for the
      2,2-diphenyl-1-picrylhydrazyl radical, as well as a reductive action, and after
      incubation for 5 days, 0.05% CA achieved a significantly higher peroxide value
      than 0.02% tert-butylhydroquinone used as a reference (P<0.05). In addition, 160
      nM CA inhibited the growth of a variety of common pathogenic microbes in humans,
      significantly inhibited fat droplet formation (P<0.05) and reduced the production
      of interleukin-1beta and tumor necrosis factor-alpha in a dose-dependent manner
      (P<0.05). Therefore, functional foods containing CA may be used as natural
      antioxidant supplements to prevent the oxidation of oil and protect human health.

PMID- 30233722
TI  - Deficiency of hypoxia inducible factor-1alpha promoted progression of diabetic
      nephropathy with hypertension.
AB  - The present study was designed to investigate the effect of hypoxia inducible
      factor-1alpha (HIF-1alpha) on diabetic nephropathy (DN) with hypertension. HIF
      1alpha deficient mice (Mx/HIF-1alpha-/-) were constructed and treated with
      streptozotocin (STZ) injection for hypertensive DN induction. Normal C57BL/6 mice
      received STZ or no treatment (normal) were considered as controls. Three days
      post STZ administration; body weight, fasting blood glucose (FBG), 24 h urinary
      albumin and systolic blood pressure (SBP) were measured weekly. Periodic acid
      Schiff's staining was performed for histologic analysis of glomeruli damage. In
      comparison with the normal control, significant upregulation and downregulation
      of HIF-1alpha was, respectively, detected in diabetic and HIF-1alpha-/- mice
      (P<0.01). In comparison with STZ-induced diabetic mice, HIF-1alpha-/- + STZ mice
      displayed reduced body weight, and increased FBG, urinary albumin and SBP. PAS
      showed HIF-1alpha-/- + STZ mice had damaged kidney tissues, with more renal
      fibrosis and apparent glomerular hypertrophy. These results demonstrated that HIF
      1alpha deficiency accelerated DN progression with increasing hypertension in
      mice.

PMID- 30233723
TI  - Ischemic colitis caused by polycythemia vera: A case report and literature
      review.
AB  - Polycythemia vera (PV) is a chronic myeloproliferative disorder originating from
      hematopoietic stem cells and complicated by thrombosis and bleeding. This report
      describes a case of ischemic colitis (IC) caused by PV and includes a review of
      the relevant literature. The patient was a 59-year-old male with a history of PV
      who presented with abdominal pain and hematochezia. Colonoscopy and
      histopathological examination results indicated suspected ischemic bowel disease.
      Following experimental anticoagulant therapy for 7 days, the patient no longer
      experienced abdominal pain and hematochezia had resolved. Colonoscopy review
      showed no obvious anomalies 1 month later. These data demonstrated that PV is an
      uncommon cause of IC.

PMID- 30233724
TI  - Antiproliferation activities of NK4 on multiple myeloma.
AB  - Multiple myeloma (MM) is a plasma cell malignancy. The hepatocyte growth factor
      (HGF) has been demonstrated to promote MM cell growth. NK4, a splice variant of
      HGF in which the heavy chain consists of the N-terminal domain and the four
      kringle domains, is a specific antagonist of HGF that competes with HGF for
      tyrosine-protein kinase receptor binding. The current study aimed to examine the
      antiproliferative activity of NK4 on human MM cells and to investigate the
      underlying mechanism. The results indicated that NK4 suppressed proliferation and
      induced apoptosis in RPMI 8226 cells. In addition, NK4 altered the expression of
      cell cycle and apoptosis-associated proteins in RPMI 8226, including cyclin
      dependent kinase 4, cyclin D1, cyclin-dependent kinase inhibitor 1B, apoptosis
      regulator Bcl-2, apoptosis regulator BAX, cleaved caspase-9 and caspase-3.
      Furthermore, NK4 inhibited the activation of the RAC-alpha serine/threonine
      protein kinase (Akt)/serine/threonine-protein kinase mTOR (mTOR) signaling
      pathway and reduced the levels of phosphorylated (p)-Akt, p-mTOR, ribosomal
      protein S6 kinase beta-1 and eukaryotic initiation factor 4E binding protein 1 in
      RPMI 8226 cells. In conclusion, NK4 inhibited the proliferation of human MM RPMI
      8226 cells, which may be attributed to the induction of apoptosis and the
      inhibition of the Akt/mTOR signaling pathway.

PMID- 30233725
TI  - Intravenous morphine titration vs. oral hydrocodone/acetaminophen for adults with
      lower extremity displaced fracture in an emergency department setting: A
      randomized controlled trial.
AB  - The objective of the present study was to test the hypothesis that intravenous
      morphine titration provides superior analgesia to oral hydrocodone/acetaminophen
      for patients with lower extremity displaced fracture in an emergency department
      (ED) setting. A prospective, randomized clinical trial of ED patients suffering
      acute lower extremity displaced fracture pain was performed with a total of 206
      participants included. After application of exclusion criteria, the cohort
      comprised 166 patients, 85 of which were randomly allocated to the oral
      hydrocodone/acetaminophen (5 mg/500 mg) group and 81 to the intravenous morphine
      titration (every 5 min by 3-mg increments) group. The main outcome was the visual
      analogue scale (VAS) at different time-points after the first dose of analgesic
      was administered. Secondary outcomes included the VAS change during the skeletal
      traction operation and short-term adverse events. The results demonstrated that
      the initial VSA of the participants was similar at the baseline on arrival at the
      ED (P=0.2582). At the time-points of 5, 15, 30 min after the first dose of
      analgesic administered, the intravenous morphine titration group exhibited a
      greater VAS reduction compared with that in the oral hydrocodone/acetaminophen
      group (P<0.01). The differences between the 2 groups were not statistically
      significant at 1 h or thereafter. The incidence of short-term adverse events was
      similar between the 2 groups but sedation, whose incidence in the morphine group
      was markedly increased, may not be arbitrarily attributed to adverse events. It
      was concluded that, compared with oral hydrocodone/acetaminophen, intravenous
      morphine titration provided a rapid and sufficient pain relief and equivalent
      short-term adverse events for patients with lower extremity displaced fracture in
      an ED setting.

PMID- 30233726
TI  - MFN2 ameliorates cell apoptosis in a cellular model of Parkinson's disease
      induced by rotenone.
AB  - A number of studies indicated that apoptosis, a specific type of programmed cell
      death, contributed to the loss of dopaminergic neurons during progression of
      Parkinson's disease (PD). Previously, the authors of the present study
      demonstrated that apoptosis of dopaminergic neurons was mainly achieved via the
      mitochondria-mediated apoptosis pathway, however, the precise molecular
      mechanisms remain to be elucidated. The present study aimed to determine whether
      mitofusin-2 (MFN2), a mitochondrial protein, participated in the apoptosis of
      dopaminergic neurons in a cellular model of PD induced by rotenone. The present
      study demonstrated that the expression of MFN2 was relatively stable following
      treatment with rotenone. Lentiviral knockdown and overexpression experiments for
      the first time, to the best of the authors knowledge, revealed that MFN2
      prevented rotenone-induced cell death by amelioration of apoptosis. These results
      revealed a protective role of MFN2 against apoptosis in an in vitro model of PD
      and may be used to establish MFN2 as a potential therapeutic target for the
      treatment of this disease.

PMID- 30233729
TI  - miRNA-146a attenuates inflammation in an in vitro spinal cord injury model via
      inhibition of TLR4 signaling.
AB  - The present study evaluated the anti-inflammatory effect of microRNA (miR)-146a
      in a spinal cord injury (SCI) rat model and in vitro model, and explored possible
      underlying mechanisms of this effect. miR-146a expression was analyzed using
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 content was measured
      using ELISA kits. Inducible nitric oxide synthase (iNOS), prostaglandin E2
      (PGE2), Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88
      (MyD88) and phosphorylated (p)-nuclear factor (NF)-kappaB were measured using
      western blotting. In the SCI rat model, miR-146a expression was downregulated. In
      the in vitro model, downregulation of miR-146a increased inflammation, enhanced
      iNOS and PGE2 protein expression and induced TLR4, MyD88 and NF-kappaB
      expression. Overexpression of miR-146a reduced inflammation, iNOS and PGE2
      protein expression, and suppressed TLR4, MyD88 and NF-kappaB expression in the in
      vitro SCI model. The inhibition of TLR4 attenuated the proinflammatory effects of
      anti-miR-146a in the in vitro SCI model. The results indicate that miR-146a
      reduces inflammation in an SCI model through the TLR4-NF-kappaB signaling
      pathway. The present study demonstrated that miR-146a may be a promising
      therapeutic agent for SCI.

PMID- 30233727
TI  - Effect of exercise on bone in poorly controlled type 1 diabetes mediated by the
      ActRIIB/Smad signaling pathway.
AB  - Myostatin (MSTN) is not only a key negative regulator of skeletal muscle
      secretion, however is also an endocrine factor that is transmitted to bone. To
      investigate the effect and possible mechanism of weight-bearing treadmill running
      on bone with poorly controlled Type 1 diabetes, rats were randomly divided into
      three groups: Normal control (NC), diabetic mellitus (DM) and diabetic exercise
      training groups (DM-WTR). The DM-WTR rats were trained with weight-bearing
      running. The results demonstrated that the levels of serum insulin, body weight,
      bone mass, muscle mass, grip strength, and serum calcium in the DM-WTR rats were
      significantly increased, whereas the levels of blood glucose, alkaline
      phosphatase, and tartrate-resistant acid phosphatase were markedly reduced in the
      DM-WTR rats compared with the DM rats. Weight-bearing running inhibited
      streptozocin (STZ)-induced MSTN mRNA and protein expression in the diabetic rats.
      The mRNA and protein expression levels of activin type IIB receptor and mothers
      against decapentaplegic homolog 2/3 and its phosphorylation in femur DM-WTR rats
      were reduced compared with DM rats. In addition, weight-bearing running enhanced
      the STZ-induced Wnt and beta-catenin expression levels and reduced the STZ
      induced glycogen synthase kinase (GSK)-3beta expression in diabetic rats' femora.
      In conclusion, the results suggested that weight-bearing running could partially
      ameliorate STZ-induced femur atrophy via MSTN downregulation, and this may be
      associated with the inactivation of Activin A Receptor Type 2B/Smad2/3 signaling
      pathways and the activation of the Wnt/GSK3beta/beta-catenin signaling pathway.
      Further studies are needed to verify these conclusions.

PMID- 30233728
TI  - Combination treatment of captopril and prazosin to treat patients with
      gestational hypertension.
AB  - Gestational hypertensive disorder is a complication of pregnancy, which adversely
      affects mother-child health. Captopril and prazosin are two agents that are
      frequently applied for the treatment of patients with gestational hypertension.
      However, the cooperative efficacy of captopril and prazosin has been not
      investigated in a previous study. In the present study, the comprehensive
      treatment of captopril and prazosin for the treatment of patients with
      gestational hypertension was investigated. A total of 324 patients with
      gestational hypertension were recruited to analyze the therapeutic effects of
      captopril and prazosin in patients with gestational hypertension. The duration of
      the treatment, dose-limiting toxicities and maximum tolerated dose of captopril
      and prazosin were examined in this cohort. Furthermore, the levels of blood
      pressure and proteinuria were also examined in patients with gestational
      hypertension who received treatment with captopril and/or prazosin with placebo
      as a control. Serum levels of vasodilation-converting enzyme and alpha-adrenergic
      receptor were also examined prior to and during the 4-week post-treatment period.
      It was observed that the most common treatment-emergence adverse events were
      hypertension and proteinuria following 4-week treatments. The data revealed that
      captopril or prazosin treatments significantly ameliorated gestational
      hypertension and symptoms compared with placebo (P<0.01). Notably, the
      combination of captopril and prazosin treatments significantly ameliorated
      hypertension and proteinuria and reduced the expression levels of vasodilation
      converting enzyme and alpha-adrenergic receptor (all P<0.01), which contributed
      to beneficial effects on complications and blood coagulation mechanism compared
      with either captopril or prazosin treatment. In conclusion, the present clinical
      study indicated that combination treatment of captopril and prazosin exhibited
      more efficient outcomes than the single agent by improving gestational
      hypertension, indicating that a comprehensive therapeutic regimen of captopril
      and prazosin may be a potential clinical opinion for patients with gestational
      hypertension.

PMID- 30233730
TI  - Clinical characteristics of occluded culprit arteries and collaterals in patients
      with non-ST-segment elevation myocardial infarction and impact on clinical
      outcomes.
AB  - The presence of an occluded culprit artery or collaterals in non-ST-segment
      elevation myocardial infarction (NSTEMI) is relatively common; however, limited
      data are available regarding their clinical significance. The aim of the current
      study was to determine the clinical characteristics of occluded culprit arteries
      and coronary collaterals in patients with NSTEMI and their impact on patient
      outcomes. A total of 345 patients diagnosed with NSTEMI via coronary angiography
      between February 2006 and May 2013 were evaluated in the present study. Patient
      demographics, procedural characteristics and clinical outcomes of patients were
      analyzed according to the presence of an occluded culprit artery and coronary
      collaterals. A total of 78 (22.6%) and 166 patients (48.1%) exhibited an occluded
      artery and coronary collaterals, respectively. The left anterior descending
      artery is a more common location of culprit arteries in patients with NSTEMI with
      patent artery (NSTEMIPA) and distal parts of the artery are more common location
      of culprit arteries in patients with NSTEMI with occluded arteries (NSTEMIOA).
      Patients with NSTEMIOA exhibited higher peak creatine kinase-MB (CKMB) and
      troponin-I levels compared with patients that had NSTEMIPA. The presence of
      coronary collaterals is associated with a lower mean left ventricular ejection
      fraction, higher regional wall motion score index and extensive coronary artery
      disease. However, the clinical outcomes of patients with collaterals did not
      differ, irrespective of the presence of an occluded culprit artery or coronary
      collaterals. In the current study, ~25% of patients with NSTEMI had an occluded
      culprit coronary artery whereas 50% of patients with NSTEMI had coronary
      collaterals. The presence of an occluded artery and/or coronary collaterals did
      not affect clinical outcomes. Further studies are required to evaluate the long
      term prognostic impact of an occluded artery and collaterals.

PMID- 30233731
TI  - Hesperidin protects against IL-1beta-induced inflammation in human osteoarthritis
      chondrocytes.
AB  - Hesperidin is a vitamin P flavonoid compound primarily present in citrus fruits,
      which possesses an anti-inflammatory effect. The functional role of hesperidin in
      interleukin (IL)-1beta-stimulated human osteoarthritis (OA) chondrocytes is still
      unknown. In the present study, anti-inflammatory effects of hesperidin in IL
      1beta-stimulated chondrocytes were investigated. The results demonstrated that
      hesperidin treatment markedly decreased nitric oxide and prostaglandin E2
      production and markedly downregulated inducible nitric oxide synthase and
      cyclooxygenase-2 expression in IL-1beta-stimulated OA chondrocytes. In addition,
      hesperidin markedly reduced IL-1beta-induced matrix metalloproteinase (MMP)-3 and
      MMP-13 expression in human OA chondrocytes. Furthermore, hesperidin markedly
      decreased the activation of nuclear factor (NF)-kappaB in human OA chondrocytes.
      In conclusion, it was revealed for the first time that hesperidin inhibited
      inflammatory responses in IL-1beta-stimulated human chondrocytes, potentially
      through inhibiting the activation of the NF-kappaB signaling pathway. These data
      suggest that hesperidin may be a potential agent for the treatment of OA.

PMID- 30233732
TI  - Dysregulated ICOS+ proinflammatory and suppressive regulatory T cells in patients
      with rheumatoid arthritis.
AB  - Regulatory T cells (Tregs) serve an important role in the pathogenesis of
      rheumatoid arthritis (RA) by regulating autoimmunity and inflammation. Humans and
      mice contain inducible T-cell costimulator-positive (ICOS+) Tregs, although their
      role in RA is unclear. A total of 33 patients with RA and 17 normal control (NC)
      subjects were examined. The proportion of ICOS+ Tregs in the peripheral blood and
      intracellular cytokine levels in these cells were assessed using flow cytometry.
      The percentage of ICOS+ Tregs increased in the cohort of patients with RA
      compared with the NCs. Such increases were much larger in patients with inactive
      RA compared with patients with active RA. Additionally, ICOS+ Tregs expressed
      multiple suppressive cytokines, including interleukin (IL)-10, transforming
      growth factor-beta and IL-35, but expressed low levels of IL-17. Importantly, the
      expression of suppressive cytokines in ICOS+ Tregs from patients with active RA
      decreased, but IL-17 expression noticeably increased compared with patients with
      inactive RA. The present findings suggested that ICOS+ Tregs may perform
      inflammatory and inhibitory functions, and abnormal ICOS+ Tregs numbers and
      functions may contribute to the pathogenesis of RA.

PMID- 30233733
TI  - Protective role of fentanyl in lipopolysaccharide-induced neuroinflammation in BV
      2 cells.
AB  - Neurosurgery always results in neuroinflammation, which may activate microglial
      cells. Previous studies have demonstrated that fentanyl could be used for the
      induction or maintenance of anesthesia prior to surgery. However, it is unknown
      if fentanyl attenuates neuroinflammation prophylactically. Cell viability in
      groups that were treated with different concentrations of fentanyl (0.01, 0.1, 1
      or 5 umol/l) was analyzed by an MTT assay. BV-2 microglial cells were treated
      with lipopolysaccharide (LPS) at a concentration of 1 ug/ml to mimic
      neuroinflammation in vitro. BV-2 cells were pretreated with 5 umol/l fentanyl
      prior to stimulation by LPS. The protein levels of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1beta and IL-10 in the culture medium were assessed by
      ELISA. The mRNA level of toll-like receptor (TLR)4 was evaluated by reverse
      transcription-quantitative polymerase chain reaction analysis. The protein levels
      of TLR4, glycogen synthase kinase (GSK)-3beta and phosphorylated (p)-GSK-3beta in
      BV-2 cells were assessed by western blot analysis. The MTT assay demonstrated
      that low concentrations of fentanyl (0.01, 0.1 or 1 umol/l) did not affect the
      cell viability of BV-2 cells, while 5 umol/l fentanyl significantly reduced BV-2
      cell viability. The results of ELISA revealed that LPS significantly upregulated
      the release of TNF-alpha, IL-1beta and IL-10, which were repressed by fentanyl
      pretreatment. Fentanyl pretreatment significantly reduced the LPS-induced
      elevation of TLR4 at mRNA and protein levels as well as p-GSK-3beta protein
      levels in BV-2 cells. In conclusion, fentanyl pretreatment protects BV-2 cells
      from LPS-induced neuroinflammation by inhibiting TLR4 expression and GSK-3beta
      activation. Neuroinflammation induced by surgery serves an important role in the
      development of postoperative cognitive dysfunction (POCD) and targeting the TLR4
      and GSK-3beta signaling pathway may provide a novel therapeutic approach for the
      treatment of POCD.

PMID- 30233735
TI  - A case of retrograde venous air embolism causing cerebral infarction following
      upper gastrointestinal endoscopy: A novel pathophysiological mechanism.
AB  - The incidence of cerebral infarction following upper gastrointestinal endoscopic
      procedures is well described in the existing literature, with most mechanisms
      involving arterial travel of the embolus. We describe a case of cerebral
      infarction not explained by previously described mechanisms and detail the
      proposed occurrence of retrograde venous air embolism causing cerebral infarction
      following an upper gastrointestinal endoscopic procedure.

PMID- 30233734
TI  - MicroRNA-365 regulates the occurrence and immune response of sepsis following
      multiple trauma via interleukin-6.
AB  - In the present study, the expression of microRNA (miR)-365 and interleukin (IL)-6
      in peripheral blood mononuclear cells and serum from patients with sepsis
      following multiple trauma has been investigated. A total of 26 patients with
      sepsis following multiple trauma were included as the experimental group, whereas
      21 contemporaneous patients without sepsis following multiple trauma were
      included as the negative control group. The expression of IL-6 mRNA and miR-365
      was determined by reverse transcription-quantitative polymerase chain reaction,
      and western blot analysis was used to measure IL-6 protein expression. ELISA was
      performed to determine the secretion of IL-6 protein. Following stimulation with
      lipopolysaccharide (LPS) for 24 h, THP-1 cells were used to examine the
      expression of miR-365 and the levels of IL-6 protein and mRNA in cells simulating
      sepsis. A dual luciferase reporter assay revealed that IL-6 mRNA was a direct
      target of miR-365. Patients with sepsis following multiple trauma exhibited
      significantly higher IL-6 mRNA and protein levels than patients without sepsis
      (P<0.05). In addition, miR-365 expression in patients with sepsis following
      trauma was significantly lower than in patients without sepsis (P<0.05). Similar
      effects were observed in THP-1 cells treated with LPS. The present study
      demonstrated that increased expression of IL-6 in patients with sepsis following
      multiple trauma is associated with decreased expression of miR-365. miR-365 may
      regulate the occurrence and immune response of sepsis following multiple trauma
      via IL-6. These results may elucidate agents for clinical diagnosis and treatment
      of the disease.

PMID- 30233737
TI  - Solid pseudopapillary tumor of the pancreas: A difficult presentation of an
      uncommon tumor.
AB  - We present a case of a solid pseudopapillary tumor of the pancreas incidentally
      discovered in a child who presented following sports-related abdominal trauma.
      This case is a unique presentation of an uncommon pancreatic tumor that posed a
      diagnostic dilemma to radiologists as it appeared as a hematoma by imaging and
      initial image-guided aspiration. Ultimately, MRI and core biopsy were needed to
      make the final diagnosis. This entity posed a problem during the differential
      diagnosis given the appearance and extenuating circumstances.

PMID- 30233736
TI  - Isolated hepatic hemangiomatosis in 2 septuagenarians.
AB  - We report 2 cases of isolated hepatic hemangiomatosis: a 76-year-old woman who
      is, to our knowledge, the oldest person with this diagnosis, and a 74-year-old
      woman. Magnetic resonance imaging of the abdomen showed T2 hyper intense lesions
      throughout the liver, peripheral nodular arterial enhancement, and filling of
      contrast on the portal venous and delayed phases. Computed tomography showed
      liver lesions with peripheral nodular enhancement in the early phase and a
      centripetal pattern or "filling in" during the late phase; the lesions opacified
      after a delay of 3 or more minutes and remained isodense or hyperdense on delayed
      scans. Both images were consistent with hepatic hemangiomatosis. These cases help
      increase awareness about benign and unusual liver lesions with radiologic
      characteristics similar to those of malignant liver tumors. The authors also
      present a review of 15 other cases of isolated hepatic hemangiomatosis reported
      in English literature from 1970 to present.

PMID- 30233738
TI  - Intermittent superior mesenteric artery syndrome in a patient with multiple
      sclerosis.
AB  - A 42-year-old man with multiple sclerosis presented with recurrent vomiting, in
      the context of recent weight loss. Computed tomography scan of the abdomen and
      pelvis revealed duodenal compression by the superior mesenteric artery (SMA),
      consistent with intermittent SMA syndrome. Subsequent gastroscopy and barium meal
      follow-through showed resolution of the obstruction. SMA syndrome is rare and has
      not previously been reported in a patient with multiple sclerosis. We hypothesize
      that loss of the aortomesenteric fat pad on the background of contorted body
      habitus from multiple sclerosis placed the patient at risk for intermittent
      positional compression of his duodenum.

PMID- 30233739
TI  - Iliac bone biopsy complicated by hematoma: Hemostasis achieved with glue
      injection.
AB  - Serious hemorrhage after a bone biopsy is a rare complication of the procedure.
      Due to the infrequency of this complication, there is limited literature
      available regarding the treatment. Here, we present a case of a 70-year-old male
      who developed a symptomatic gluteal hematoma after an iliac bone lesion biopsy.
      Hemostasis was achieved by injecting an N-butyl cyanoacrylate glue solution into
      the bone cannulation site under CT-guidance.

PMID- 30233740
TI  - A case report of acalculous cholecystitis due to Salmonella paratyphi B.
AB  - Acute acalculous cholecystitis (AAC) is a rare condition occurring in only 5%-10
      % of patients with acute cholecystitis. Systemic illness caused, for example, by
      E coli, Klebsiella pneumoniae, Vibrio cholera, and Salmonella species can result
      acute inflammation of gallbladder wall. It is a surgical emergency and if left
      untreated can lead to high mortality due to gangrene or perforation of
      gallbladder. We managed a 60-year-old female with clinical presentation of acute
      cholecystitis caused by Salmonella-induced gastroenteritis. Prompt use of
      radiological modalities such as computer tomography (CT scan) and ultrasound
      played an important role in pathologic diagnosis, overall follow up, and
      management of the patient.

PMID- 30233741
TI  - Percutaneous transgluteal computed tomography-guided aspiration of obturator
      internus pyomyositis in adolescent athlete: A case report and literature review.
AB  - Pyomyositis is an uncommon infection of muscle that is usually managed
      conservatively, but, can progress to abscess formation requiring open surgical
      drainage. We present the first reported case of a 14-year-old male with obturator
      internus pyomyositis requiring computed tomography-guided percutaneous
      transgluteal drainage for the management of a right obturator internus abscess.
      We present this case report to provide an alternative to the open surgical
      management of abscesses from pyomyositis by means of successful computed
      tomography-guided drainage.

PMID- 30233742
TI  - A rare anatomical variation of great saphenous vein at the level of
      saphenofemoral junction.
AB  - The saphenofemoral junction is one of the major connections between the
      superficial and deep venous system in the leg. It is important to understand the
      anatomic variations in the lower extremity for treatment of venous disorders.
      There are many variations of the superficial system, most of them are with the
      great saphenous vein. A rare anatomic variant where the great saphenous vein is
      located between the superficial femoral and profunda arteries at the level of
      saphenofemoral junction is discussed in our case report.

PMID- 30233743
TI  - Successful embolization of ileal conduit stomal varices with N-butyl
      cyanoacrylate via a recanalized paraumbilical vein.
AB  - A 77-year-old woman with liver cirrhosis was admitted to our hospital for marked
      hemorrhage in her ileal conduit stoma. She had a history of cystectomy and
      urinary diversion for bladder carcinoma 2 years ago. Contrast-enhanced CT
      demonstrated varices in the ileal conduit stoma. We accessed the varices via a
      recanalized paraumbilical vein to avoid pain from the transhepatic approach, and
      selectively embolized the varices with N-butyl cyanoacrylate (NBCA). We consider
      antegrade embolization of ileal conduit stomal varices with NBCA to be effective
      and feasible. Access via a paraumbilical vein is a useful alternative to the
      transhepatic approach.

PMID- 30233744
TI  - Atypical chronological changes on neuroimaging in the epidermoid in the frontal
      lobe with intracystic hemorrhage and tumor growth: Case report.
AB  - Intracranial epidermoids are rare lesions accounting for 0.2%-1.8% of all
      intracranial tumors. They commonly develop in the cerebellopontine angle and the
      parasellar region and can appear with atypical neuroimaging features due to
      intracystic hemorrhages which complicate diagnosis. The authors present a case of
      a 62-year-old woman with a frontal epidermoid cyst with a hemorrhage and tumor
      growth. A series of atypical radiological findings showed gradual changes in the
      lesion appearance that were confirmed with surgery and histopathology. To avoid
      surgical complications such as chemical meningitis, it is important to remember
      that epidermoid cysts occasionally bleed, leading to atypical MRI and/or CT
      findings and diagnostic difficulties. Development of epidermoid cysts in atypical
      locations in the brain may result in challenges to accurate diagnosis.

PMID- 30233745
TI  - Diagnosis of gastric subepithelial mass as an accessory spleen using fusion of
      spleen SPECT and CT images.
AB  - More than 10% of the healthy population has one or more accessory spleens. An
      accessory spleen can be mistaken for a gastric subepithelial mass, and may not be
      differentiated by CT or endoscopic ultrasonography (EUS). A gastric subepithelial
      mass was detected on routine endoscopy in a 52-year-old man with a history of
      splenectomy 10 years previously for trauma. Subsequent EUS and CT located the
      subepithelial mass on the fourth layer of the stomach fundus. A definitive
      diagnosis was obtained by performing technetium-99m (99mTc-)-labeled denatured
      red blood cell (RBC) scintigraphy. Fusion images were obtained by combining the
      digital CT and SPECT images on a computer workstation. Here, we report the use of
      spleen SPECT and CT fusion images to diagnose a case of accessory spleen
      mimicking a gastric subepithelial mass, thereby avoiding the need for an invasive
      procedure.

PMID- 30233746
TI  - Bleeding after interstitial brachytherapy for cervical cancer requiring
      embolization.
AB  - Cervical cancer is the third most common cancer among women worldwide and is
      usually managed with chemoradiation in advanced disease. This case presents a 41
      year-old female with locally advanced cervical cancer who underwent combination
      intracavitary/interstitial brachytherapy after chemoradiation for local disease
      control. At her fifth brachytherapy session, one of the interstitial needles was
      malpositioned and lead to vascular injury with significant blood loss. She
      subsequently underwent emergent embolization of a branch of the right obturator
      artery with immediate clinical improvement and no complications. This is the
      first reported case of vascular injury from an interstitial brachytherapy needle
      that required arterial embolization for hemostasis.

PMID- 30233747
TI  - Bilateral congenital absence of the internal carotid arteries: a case report.
AB  - Congenital absence of the internal carotid artery is a rare occurrence. Even more
      infrequent are cases where the patient has a bilateral absence of the internal
      carotid arteries. Reported is a case of a 52-year-old woman who presented with
      optic nerve neuropathy, and was incidentally discovered to have a congenital
      bilateral absence of her internal carotid arteries. During computed tomography
      angiography imaging looking for cerebral venous thrombosis, related to her
      preexisting condition of bilateral elevated optic discs and residual left optic
      neuropathy, the findings were made. The absence of the arteries is not always
      recognizably symptomatic, with most findings being incidental through imaging
      studies only. This is because collateral flow allows for sufficient cerebral
      circulation. However, this condition puts such patients at higher risk for
      conditions such as aneurysms and subsequently strokes where the collateral flow
      exists.

PMID- 30233748
TI  - Uterine anteversion after uterine fibroid embolization.
AB  - Uterine fibroid embolization has been proven effective in treating symptomatic
      uterine fibroids for appropriately selected patients as an alternative option to
      surgical approaches. The most common adult uterine position is anteverted
      followed by a retroverted uterus which can be found in roughly 15%-20% of normal
      adult females. The positioning of the uterus can change from anteversion to
      retroversion due to the filling of bladder or during pregnancy; however, changing
      from retroverted to anteverted position without prior pregnancy or endometriosis
      is rather uncommon. Here, we describe a case of uterine orientation change from
      retroversion to anteversion presenting 6 months after uterine fibroid
      embolization.

PMID- 30233749
TI  - Magnetic resonance imaging findings in ovarian torsion post in vitro
      fertilization.
AB  - Patients who get pregnant after being treated with in vitro fertilization (IVF)
      are at significantly increased risk of ovarian torsion compared to the general
      population and also in comparison to patients who get pregnant normally [1,2].
      The risk is further increased in patients who develop ovarian hyperstimulation
      syndrome [1]. This possibility should be considered in this group of patients
      presenting with acute abdominal pain and immediate management should be
      commenced. Here, we report 2 patients who received treatment for infertility with
      IVF and developed ovarian torsion and we discuss their management including the
      imaging workup. The first case is a 34-year-old woman at 11 + 3 weeks of
      gestation after IVF who presented with a 12-hour acute right lower abdominal pain
      with nausea and vomiting. She underwent an ultrasound examination and then
      further evaluated with magnetic resonance imaging which showed asymmetric
      enlargement of the right ovary and stromal edema and a diagnosis of ovarian
      torsion was made. The patient underwent laparoscopic detortion and the ovary was
      salvaged. The second case is a 33-year-old woman at 9 weeks of gestation after
      IVF who presented with intermittent abdominal pain, vaginal bleeding, and nausea
      and vomiting for 5 days but became worse on the fifth day. Ultrasound and
      subsequently magnetic resonance imaging were performed which confirmed
      hyperstimulation syndrome. Abnormal location of the left ovary anterior to the
      uterus with higher volume as well as the clinical progression raised the
      possibility of ovarian torsion and prompted a diagnostic laparoscopy which showed
      right ovarian torsion and detortion was performed.

PMID- 30233750
TI  - A ventriculoperitoneal shunt incidentally found in the stomach.
AB  - We report a case of a ventriculoperitoneal shunt incidentally found within the
      stomach while the patient was undergoing a percutaneous endoscopic gastrostomy
      (PEG) tube placement. Among the complications of ventriculoperitoneal shunt
      placement, bowel perforation is rare a complication found in 0.01%-0.07% of
      cases, and typically occurs in premature infants and neonates [1]. To date, less
      than 100 such cases have been recorded of which only a few have appeared in the
      radiological literature. Here we discuss the current literature, the radiological
      features, clinical presentations and the management.

PMID- 30233751
TI  - Hamate-pisiform coalition complicated by fracture in a pediatric patient.
AB  - Coalition of the carpal bones is a relatively uncommon anatomic anomaly. The
      majority of carpal coalitions occur between the lunate and triquetrum. There are
      rare reports of coalition involving the hamate and pisiform. We report a case of
      a previously asymptomatic male who sustained minor trauma and was found to have
      hamate-pisiform coalition complicated by a minimally displaced pisiform fracture.

PMID- 30233752
TI  - Breast metastasis from ovarian cancer: A case report.
AB  - Breast metastasis from ovarian cancer is a rare event, with vary clinical and
      imaging presentations, depends on the form of dissemination of the disease and
      may mimic primary benign and malignant lesions.Confirmation of the diagnosis is
      of pivotal importance to choice an adequate therapeutic planning, allowing to
      avoid unnecessary surgeries and to provide appropriate systemic therapy. In this
      manuscript, we present a case of breast metastasis from ovarian cancer. The
      patient presented to our Institute with a localized, palpable mass in the upper
      outer quadrant of the right breast. Mammography and breast sonography showed a
      singular, round, and homogenous mass with regular borders. No suspicious axillary
      node was observed. Lesion biopsy revealed the presence of epithelial malignant
      tumor cells, compatible with a tube-ovarian serous histotype. So, although it
      could be rare, secondary malignant neoplasm should be considered in the
      differential diagnosis of breast lesions in patients with a personal history of
      ovarian cancer.

PMID- 30233754
TI  - Fibromatosis arising from the pectoralis major muscle mimicking breast cancer.
AB  - Fibromatoses are soft tissue tumors composed of fibroblasts which commonly appear
      in the muscular aponeurosis of the abdomen. Mammary fibromatoses occur in only
      0.2% of breast neoplasms and have been reported in association with prior breast
      augmentation and Gardner's syndrome. Multiple imaging modalities have been used
      to characterize the appearance of breast fibromatosis; however, it remains a
      tissue diagnosis given the variability both within and across modalities. We
      present the case of a 25-year-old female with a history of palpable breast mass
      who was evaluated with ultrasound, diagnostic mammography, MRI, and CT.
      Ultrasound-guided biopsy revealed fibromatosis, and MRI ultimately revealed that
      the mass was arising from the pectoralis major muscle and extensively involved
      the chest wall.

PMID- 30233755
TI  - Intracranial and systemic manifestations of familial leptomeningeal amyloidosis,
      as seen on CT and MRI.
AB  - Leptomeningeal amyloidosis is a subset of familial transthyretin amyloidosis, a
      family of diseases occurring in conjunction with multiple known mutations of the
      transthyretin gene. Though this is primarily a disease of the central nervous
      system, amyloid deposition is multisystemic. We describe a case of a 61-year-old
      man with known central nervous system amyloidosis presenting to the emergency
      room with stroke-like symptoms, including left hemineglect, right gaze paresis,
      and left hemiplegia, atop baseline dementia. A noncontrast CT head demonstrated
      ventriculomegaly and no acute hemorrhage. Urinalysis indicated an underlying
      urinary tract infection, ultimately believed to have prompted a breakthrough
      seizure. Electroencephalogram revealed diffuse encephalopathy. Contrast-enhanced
      MRI demonstrated hallmarks of intracranial amyloid with no new infarct.
      Previously taken noncontrast CT neck and thorax demonstrated evidence of systemic
      disease.

PMID- 30233753
TI  - Pulmonary vein thrombosis in patients with medical risk factors.
AB  - Pulmonary vein thrombosis in patients with medical illnesses has been rarely
      reported, and it is also rarely reported in those with no risk factors. We report
      2 patients with pulmonary vein thrombosis, 1 with metastatic renal cell carcinoma
      and 1 with presumed pulmonary aspergillosis. Thrombi or tumors in a pulmonary
      vein are clinically important because they may cause systemic embolism or
      hemoptysis.

PMID- 30233756
TI  - Asymptomatic endophthalmitis following strabismus correction in a pediatric
      patient.
AB  - Endophthalmitis is most commonly seen in adults shortly after cataract surgery.
      It is rare in the pediatric population. Presented here is a case of
      endophthalmitis following strabismus repair in a 9-month-old patient with Trisomy
      21. Leukocoria was observed 15 days after surgery, but the child did not exhibit
      symptoms of infection, and the ordering clinician requested an MRI of the brain
      and orbits to assess the possibility of retinoblastoma. This case highlights the
      importance of MRI in the evaluation of leukocoria and displays typical MRI
      findings of this infrequently-encountered condition in the pediatric population.

PMID- 30233757
TI  - Reactivation tuberculosis presenting with unilateral axillary lymphadenopathy.
AB  - Unilateral axillary lymphadenopathy has various benign and malignant etiologies.
      Although benign causes are more common, it is important to exclude malignant
      causes, including metastasis from primary breast carcinoma. Benign etiologies
      include reactive adenopathy, granulomatous disease, and collagen vascular
      disease. We present a case of unilateral right axillary lymphadenopathy in a
      patient with rheumatoid arthritis. The pathologic diagnosis of granulomatous
      lymphadenitis and interval discovery of patient's history of latent tuberculosis
      led to a second biopsy for special mycobacterial staining and cultures with a
      final diagnosis of reactivation tuberculosis. The extrapulmonary manifestation of
      reactivation tuberculosis with tuberculous lymphadenitis is uncommon and
      particularly rare in the axillary lymph nodes.

PMID- 30233758
TI  - Mediastinal extension of a pancreatic pseudocyst.
AB  - A 50-year-old man with a history of chronic pancreatitis due to alcoholism
      presented with dyspnea, at which time he was diagnosed with pleural effusions,
      treated, and discharged. Two months later, he was readmitted with hemoptysis and
      abdominal pain. CT and MRI of the chest demonstrated a mediastinal cystic mass
      that communicated with the retroperitoneum. Ultrasound-guided aspiration of the
      cystic mass revealed high levels of amylase, confirming that the mass was a rare
      pancreatic pseudocyst extending into the mediastinum.

PMID- 30233759
TI  - Bifid ureter with blind-ending branch: A rare anatomic variant detected during
      antegrade ureteric stent insertion.
AB  - Anatomic variants of the urinary tract are relatively common; however, a bifid
      ureter with a blind-ending branch is a rare congenital anomaly. This variant
      often goes unnoticed because patients are either asymptomatic or complain of
      vague abdominal symptoms. Diagnosis is often incidental, and may be missed on
      conventional imaging. Although bifid ureters usually do not require any specific
      investigations or treatment; it is important to have an appreciation for these
      anomalies particularly if radiological intervention or surgical procedures are
      planned. We describe a case of a blind-ending bifid ureter in a patient with
      bilateral hydronephrosis secondary to a large cervical malignancy. The presence
      of the bifid ureter was only appreciated during a technically challenging
      antegrade ureteric stent insertion several weeks after diagnosis. We review the
      clinical significance, embryology, and radiology findings of this anomaly, as
      well as the implications during radiological interventional procedures.

PMID- 30233760
TI  - Bile leak after transjugular liver biopsy in a cholecystectomy patient.
AB  - Introduction: Transjugular liver biopsy (TJLB) is a minimally invasive procedure
      performed to obtain hepatic tissue in patients whom standard percutaneous liver
      biopsy is contraindicated due to abnormal coagulation profile and/or severe
      ascites. Additionally, it has the advantage of simultaneously measuring the
      hepatic venous pressures. Case Presentation: 61-year-old male with history of
      pulmonary fibrosis, cholecystectomy and Hepatitis C underwent transjugular liver
      biopsy (TJLB) as part of his lung transplant workup. Shortly after the procedure,
      the patient developed sharp right upper abdominal pain. Immediate CT of the
      abdomen and pelvis showed small foci of contrast and gas in the gallbladder fossa
      and porta hepatis indicating hepatic capsular penetration without perihepatic
      hematoma or other evidence of hemorrhage. Follow up CT of the abdomen and HIDA
      scan confirmed the presence of bile leak. Sphincterotomy and stent placement
      through ERCP was performed. Conclusion: Bile leak after a TJLB is a rare,
      however, potential complication. ERCP and biliary stent seems an effective
      treatment for persistent symptomatic bile leak post TJLB.

PMID- 30233761
TI  - Unique neuroradiological findings in propionic acidemia.
AB  - Propionic acidemia is a rare metabolic disorder that affects the catabolism of
      branched-chain amino acids and oddchain fatty acids. Propionic acidemia is one of
      the least common organic acidemias. Presented here are manifestations not
      previously characterized. The first case is an infant with diffuse subcortical
      diffusion restriction and vermian atrophy. The second case is an adolescent with
      asymmetric cortical volume loss and contralateral cortical diffusion restriction.
      These unique brain MRI findings of propionic acidemia may aid the
      neuroradiologist in guiding genetic testing for occult metabolic disease.

PMID- 30233762
TI  - Pulmonary embolism and megaloblastic anemia: is there a link? A case report an
      literature review.
AB  - Many factors have been associated with venous thromboembolism. Among them,
      vitamin B12 deficiency can produce elevated homocysteine levels, which is a risk
      factor for venous embolism, since the latter interferes with the activation of Va
      coagulation factor by activation of C protein. We present a case of a patient
      with metabolic syndrome with apparently unprovoked pulmonary embolism. After
      careful evaluation, megaloblastic anemia was detected. Even though the patient
      had biochemistry findings of hemolysis and blood smear did not showed fragmented
      erythrocytes, which is consistent with pseudo-microangiopathic hemolytic anemia.

PMID- 30233763
TI  - Scar sarcoidosis: A rare entity found by 18F-FDG-PET/CT.
AB  - 18F-labeled fluoro-2-positron deoxyglucose emission tomography/computed
      tomography has been widely used in malignancy assessment, however, is not tumor
      specific and may be taken up by non-malignant conditions such as sarcoidosis.
      Sarcoidosis is a systemic inflammatory disorder and scar sarcoidosis is a rare
      manifestation of the disease. A 60-year-old man with a past medical history of
      synchronous colon adenocarcinoma and clear cell renal cell carcinoma with
      clinical suspicion of tumor recurrence. 18F-labeled fluoro-2-positron
      deoxyglucose emission tomography/computed tomography scan demonstrated lesions
      with increased fluorodeoxyglucose uptake in mediastinal and left supraclavicular
      lymph nodes, along with hypermetabolic cutaneous foci that corresponded with
      previous surgical scars. Skin biopsy was suggestive of sarcoidosis.

PMID- 30233764
TI  - Corrigendum: Bilateral plantar deep cleft.
AB  - [This corrects the article DOI: 10.11604/pamj.2017.28.312.14502.].

PMID- 30233765
TI  - Water, Human Rights, and Reproductive Justice: Implications for Women in Detroit
      and Monrovia.
AB  - Access to safe water and adequate living standards are recognized as basic health
      requisites and human rights worldwide. Nevertheless, socially marginalized women
      across the globe are currently facing threats to safe water access, which has
      dire implications for their health and that of their children. The City of
      Detroit, Michigan has recently shut off water services to over 50,000 residences,
      with low-income and racially marginalized women and their families
      disproportionately affected. The conditions for many Detroit residents are not
      unlike those in Monrovia, Liberia, where lack of access to safe water and
      substandard environments have contributed to the ongoing Ebola epidemic and
      subsequent maternal and infant mortality. Utilizing a comparative analytic
      approach rooted in postcolonial feminist theory and intersectionality, our
      commentary draws parallels between these two timely water, human rights, and
      reproductive justice crises in Detroit and Monrovia. We explore how public
      discourse and proposed solutions have failed to acknowledge the historical
      contexts and sociopolitical determinants of these crises, which have urgent and
      long-lasting implications for women's reproductive health and social justice
      worldwide.

PMID- 30233766
TI  - Private provision of social insurance: drug-specific price elasticities and cost
      sharing in Medicare Part D.
AB  - We explore how private drug plans set cost-sharing in the context of Medicare
      Part D. While publicly-provided drug coverage typically involves uniform cost
      sharing across drugs, we document substantial heterogeneity in the cost-sharing
      for different drugs within privately-provided plans. We also document that
      private plans systematically set higher consumer cost sharing for drugs or
      classes associated with more elastic demand; to do so we estimate price
      elasticities of demand across more than 150 drugs and across more than 100
      therapeutic classes. We conclude by discussing the various channels that likely
      affect private plans' cost-sharing decisions.

PMID- 30233767
TI  - SupplAzithromycin for Prevention of Graft-Versus-Host Disease: A Randomized
      Placebo-Controlled Trial.
AB  - Background: Allogeneic hematopoietic stem cell transplantation has been used
      widely to treat various types of malignant and non-malignant disorders. Graft
      versus-host disease is one of the main complications of this procedure which is
      associated with considerable mortality and affects quality of life. Despite
      careful selection of HLA-matched donors and implementing immunosuppressive
      therapy, the incidence rate of graft-versus-host disease remains high. Macrolide
      antibiotics are well-known immunomodulatory agents and have been effective as
      prophylaxis for graft-versus-host disease in preclinical studies. Materials and
      Methods: Ninety-six adult patients with acute leukemia were recruited into a
      double-blind, randomized, placebo-controlled trial. All patients were first-time
      transplant candidates for a full-matched related or unrelated donor. Patients
      were allocated to receive azithromycin 500 mg daily (n=48) or placebo (n=48) from
      day -6 to +12. All patients received high-dose chemotherapy, standard
      immunosuppressive regimen and supportive care according to institutional
      protocols. Results: The incidence of acute graft-versus-host disease grade III-IV
      and chronic graft-versus-host disease garde I-III was not significantly different
      between the two study arms. Oral mucositis grade 1-3 occurred in significantly
      lower number of patients in the azithromycin group compared with placebo.
      Conclusion: Based on the results of this study, protective effect of azithromycin
      on graft-versus-host disease could not be demonstrated.

PMID- 30233768
TI  - A Double-Blind, Randomized Comparison Study between ZytuxTM vs MabThera(r) in
      Treatment of CLL with FCR Regimen: Non-Inferiority Clinical Trial.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is characterized by accumulation
      of B cells in blood, lymphoid tissues and bone marrow. Addition of rituximab to
      CLL chemotherapy regimens has been associated with improved survival. The aim of
      this study was to establish efficacy and safety of ZytuxTM in comparison to
      MabThera(r) in treatment of CLL. MATERIALS AND METHODS: Seventy CLL patients who
      met the criteria for entering the study were randomized into two groups (35
      patients in each group). Both groups received Fludarabine and Cyclophosphamide
      plus Rituximab as part of the FCR regimen. Group A was treated with ZytuxTM, and
      group B was treated with MabThera(r). A non-inferiority margin of 20% for the
      primary outcome was defined to examine the similarity between ZytuxTM and
      MabThera(r). RESULTS: Baseline demographic characteristics showed no
      statistically significant difference between the two groups. The two treatment
      groups were comparable in terms of laboratory and clinical findings, cellular
      index changes and CD (5, 19, 20 and 23) counts during therapy cycles and at the
      end of the treatment period. Regarding safety results, ZytuxTM demonstrated a
      similar profile of adverse reactions in comparison to MabThera(r). Moreover, the
      overall response rate was 88% and 89% for ZytuxTM and MabThera(r), respectively
      (CI -0.17, 0.18). CONCLUSION: Results showed non-inferiority of ZytuxTM in terms
      of efficacy and adverse events as a biosimilar version of MabThera(r).

PMID- 30233769
TI  - Hemo-Lymphopoietic Malignancies Surround the Women of the Family: A Case Report
      and Literature Review.
AB  - The co-occurrence of different types of hemo-lymphopoietic malignancies within a
      family provides clues about the pattern of inheritance and common environmental
      risk factors. A family presented with developing hemo-lymphopoietic cancers in
      three female first-degree relatives: a mother and her daughters. Case 1 was
      diagnosed with Walden Strom's macroglobulinemia at age 57. Case 2 and 3 presented
      with chronic myelogenous leukemia at age 32 and diffuse large B-cell lymphoma at
      age 28, respectively. There were not any significant common environmental risk
      factors in this family, but all three cases suffered from skin dermatitis and one
      of them, who suffered from chronic myelogenous leukemia, was diagnosed with
      morphea. This family had a sedentary and stressful lifestyle. Genetic is the
      foundation of some familial aggregation of cancers. Common lifestyle habits and
      environmental etiologies are important. Morphea as an autoimmune disease could
      have the essential role in developing hematolymphoid malignancies.

PMID- 30233770
TI  - Alopecia Areata and Demyelination as Paraneoplastic Manifestation in Paediatric
      Hodgkin's Lymphoma.
AB  - Hodgkin's Lymphoma is one of the commonly encountered lymphomas in childhood.
      Most of the children present with lymphadenopathy. A rare subset of children do
      present with constellation of atypical symptoms as paraneoplastic syndromes. We
      hereby present an 11-year-old boy with classical Hodgkin's Lymphoma associated
      with Alopecia areata and demyelination as paraneoplastic manifestations. Both
      these paraneoplastic manifestations improved after initiating chemotherapy (ABVD
      regimen). A high index of suspicion for underlying malignancy would help
      clinicians in clinching an early diagnosis and would avert the associated
      complications.

PMID- 30233771
TI  - Investigation of CCR7 Marker Expression Using Immunohistochemical Method and Its
      Association with Clinicopathologic Properties in Patients with Breast Cancer.
AB  - Background: Breast cancer is one of the most common cancers among women in the
      world, especially in Iran. There are large numbers of molecular and genomic
      factors causing breast cancer as well as many markers associated with tumor
      invasion. Chemokines are small proteins that primarily regulate leukocyte
      trafficking in the homeostatic conditions and specific immune responses.
      Chemokine receptor 7 (CCR7) belongs a class A subtype 7-span transmembrane G
      protein coupled receptor. CCR7 plays a role in the migration of tumor cells such
      as immune cells into lymphoid organs through binding to its only two ligands
      CCL19/CCL21. High expression of this marker has been observed in breast cancer.
      However, there have been limited and contradictory data in studies conducted on
      the relationship between the increasing expression of this marker with various
      clinical and pathological factors. Materials and Methods: This case-control
      practical study was carried out on total mastectomy samples from 70 patients with
      breast cancer and tumor-adjacent normal tissue using immunohistochemistry
      technique to assess the expression of CCR7 marker. The relationship among the
      marker expression with different clinical and pathological tumor factors such as
      age, tumor size, microscopic grade, neurovascular invasion, lymph node metastasis
      and tumor stage were evaluated in all patients. Since the both groups were
      matched for age, so McNemar test, Chi-square test and Fisher's exact test were
      used to compare the expression of CCR7 marker in the case and control groups.
      Conditional logistic regression was employed to compare the effects of other
      variables regarding the age harmonization. Results: CCR7 expression was observed
      in 63 (91.4%) out of 70 studied patients and in tumor-adjacent normal tissue of
      55 patients (78.6%), while the marker expression intensity in normal tissue was
      lower than tumoral tissue (P<0.032) There was a significant relationship among
      the expression of CCR7 marker with disease stage (P<0.001), grade (P<0.035),
      lymph node metastasis (P<0.003), perineural invasion (P<0.037) and vascular
      invasion (P<0.01), but no significant relationship was found among CCR7
      expression with other tumor clinicopathologic parameters such as age (P>0.19) and
      tumor size (P>0.105). Conclusion: Increased expression of CCR7 has a significant
      relationship with disease stage, grade, lymph node metastasis and neurovascular
      invasion of breast cancer but has no relationship with age of patients and tumor
      size. Therefore, this biomarker can be utilized as a predictive factor for tumor
      metastasis and survival of patients.

PMID- 30233772
TI  - A Review of Allogeneic Hematopoietic Stem Cell Transplantation in Metastatic
      Breast Cancer.
AB  - Breast cancer (BC) has a high mortality rate and metastatic BC is almost
      incurable despite hormonal therapy and chemotherapy. The second and third lines
      of chemotherapies usually yield transient responses and the median survival is
      generally as low as 18-24 months. Autologous and allogeneic hematopoietic stem
      cell transplantation (HSCT) have been extensively investigated in this setting.
      The presence of immune mediated anti-tumor effects referred to as graft-versus
      tumor (GvT) effects after allogeneic HSCT among patients with solid tumors have
      been clearly defined. The advantages of allogeneic HSCT over autologous HSCT for
      metastatic BC are i) cancer-free graft and ii) immune-mediated GvT effects
      mediated by human leukocyte antigen compatible donor T-cells. In conclusion, a
      GvT effect does exist against metastatic BC and play a key role in tumor
      response. This review aims to describe the background, rationale, and clinical
      results of allogeneic HSCT as a potential alternative treatment in metastatic BC.

PMID- 30233773
TI  - Cholelithiasis in Thalassemia Major Patients: A Report from the South-East of
      Iran.
AB  - Background: Cholelithiasis and its predisposing factors are less characterized in
      thalassemia syndromes. In the present study, we assessed the prevalence of
      gallstones and related-risk factors among thalassemia major (TM) patients in
      south-east of Iran. Materials and Methods: The patients were recruited form a
      single center in Zabol city, south-east of Iran. Demographic and clinical
      information were retrieved from medical histories. Abdominal ultrasonography was
      performed to scrutinize gallstones and organ dimensions of liver, spleen,
      gallbladder and kidney. Results: The study participants (n=127) consisted of 50
      (39.4%) males and 77 (60.6%) females. The mean age of the patients was 15.2+/-7.9
      years. Cholelithiasis was observed in 11 (8.7%) patients. Cholelithiasis was
      significantly associated with age (P=0.002) and splenectomy (P=0.001). The
      patients with cholelithiasis received a significantly higher blood volume than
      patients without cholelithiasis (546+/-108.7 ml and 425.1+/-134.7 ml,
      respectively, P=0.007). There were significant differences between cholelithiasis
      and non- cholelithiasis TM patients regarding the length of right and left liver
      lobes (P=0.001), as well as the length of gallbladder (P=0.006). Ferritin level
      was not associated with cholelithiasis in our patients. In multivariate analysis,
      age older than 15 (OR=10.4, 95% CI: 1.2-86.3, P=0.02) and 30 years old (OR=42.6,
      95% CI: 2.9-613, P=0.006), and splenectomy (OR=8.7, 95% CI: 2.1-35.4, P=0.002)
      were significant risk factors for cholelithiasis. Conclusion: Cholelithiasis is a
      relatively common complication among TM patients in our region. The most
      prominent risk factors of cholelithiasis were advanced age, splenectomy and large
      volume blood transfusion.

PMID- 30233774
TI  - The Confirmation of Safety for the Intensified Conditioning Regimens: A
      Retrospective Study of Allogeneic Hematopoietic Stem Cell Transplantation for Non
      Remission Hematological Malignant Diseases.
AB  - Background: The prognosis of allogeneic hematopoietic stem cell transplantation
      (HSCT) for non-remission hematological malignant diseases is usually unfavorable.
      The most uncontrollable factor is residual disease or relapse. To overcome this
      problem, intensified conditioning regimens- sequential and/or additional
      chemotherapy to the standard regimen- could be effective. However, increasing the
      intensity of conditioning might also lead to more complications. Materials and
      Methods: We retrospectively analyzed 81 patients with non-remission disease who
      received allogeneic HSCT in our institution between 2007 and 2011. Results: 55.6%
      in 36 myeloablative conditioning patients and 46.7% in 45 reduced-intensity
      conditioning patients received intensified conditioning. The 5-year probability
      of overall survival was 35.0% and 17.1% in the standard and intensified group,
      respectively (p=0.027). Relapse mortality was 30% in the standard regimen group
      and 36.6% in the intensified regimen group (p=0.54). Transplant-related mortality
      (TRM) at 30 and 100 days was 5%, 17.1% (p=0.086) and 27.5%, 34.2% (p=0.52) in the
      standard and intensified group, respectively. There was no difference in TRM
      between the 2 groups at 30 days and 100 days. Conclusion: The results of the
      study confirm the safety of the intensified conditioning regimen. Meanwhile, it
      could be considered as one of the few methods available to reduce the tumor
      burden before HSCT for refractory malignant diseases.

PMID- 30233775
TI  - T-Cell Prolymphocytic Leukemia: An Experience from a Tertiary Cancer Centre in
      South India.
AB  - Background: T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy
      with dismal prognosis. Most patients have increased lymphocyte count
      (>1,00,000/dL) and widespread disease at presentation. Despite high response rate
      seen with alemtuzumab, the disease relapse is inevitable. Materials andMethods:
      This was a retrospective observational study done at a tertiary cancer center in
      South India. All patients diagnosed with T-PLL from August 2010 to July 2015 were
      studied for the clinical characteristics, pathological findings and treatment
      outcomes. Results: Seven patients were diagnosed as T-PLL over a period of 5
      years. The median age at diagnosis was 51 years. In the present series, 6
      patients (86%) had splenomegaly and 3 had hepatomegaly (43%). Generalized
      lymphadenopathy was seen in 4 (57%) patients at presentation. Skin lesions were
      seen in 5 (71%) patients, whereas pleural effusion was seen in only one patient
      (14%). All had elevated total leukocyte count, with more than 1, 00,000/dL in 4
      patients. The median survival was 5 months with different chemotherapy (CT)
      regimens (5 patients treated with CT and 2 received best supportive care).
      Conclusion: T-PLL is a rare disease with no definite treatment guidelines. At
      present, the best outcomes are achieved if treatment with alemtuzumab is followed
      by stem cell transplant, but the disease invariably relapses. Countries where
      affordability remains a big challenge, the best approach needs to be defined
      beyond the monoclonal antibodies and transplant.

PMID- 30233776
TI  - Bevacizumab Inhibits Angiogenic Cytokines in Head and Neck Squamous Cell
      Carcinoma: From Gene to the Protein.
AB  - Background: Head and neck squamous cell carcinoma (HNSCC) is one most prevalent
      cancers among worldwide. Aim of this study was to evaluate possible effect of
      bevacizumab, a vascular endothelial growth (VEGF) factor monoclonal antibody on
      HNSCC cells in vitro to evaluate angiogenic profile changes. Materials and
      Methods: HNSCC cells were grown and after that different concentrations of
      bevacizumab were added in order to evaluate cytotoxic concentration using MTT
      assay. Then after, the cultured cells in presence of different concentration of
      bevacizumab were evaluated for gene expression of VEGF, matrix metalloprotease-2
      (MMP-2) and MMP-9 using real time polymerase chain reaction (PCR). Moreover, the
      VEGF expression was evaluated by enzyme-linked immunosorbent assay (ELISA).
      Results: The concentration at which half cells died (IC59) was calculated 1779
      ug/mL and at this concentration, VEGF protein secretion was decreased by over one
      fold. RT-PCR results showed that MMP2, MMP9 and VEGF decreased by 1, 0.6 and 1.1
      folds, respectively. Conclusion: It seems that bevacizumab could be considered as
      a side therapy for patients with HNSCC due to its potential for inhibition of
      angiogenic related factors, but further complementary studies are necessary.

PMID- 30233777
TI  - Factors Affecting the Incidence and Severity of Oral Mucositis Following
      Hematopoietic Stem Cell Transplantation.
AB  - Background: Patients who receive hematopoietic stem cell transplantation (HSCT)
      experience several complications that oral mucositis (OM) is a frequent symptom.
      This study was designed to evaluate the incidence, risk factors, prophylaxis and
      treatment strategies for established OM. Materials and Methods: We included 173
      adult patients who received autologous or allogeneic hematopoietic stem cell
      transplantation in this study. The World Health Organization oral toxicity scale
      was used to assess the severity of OM. Patients received two prophylactic
      regimens: regimen 1 contained nystatin, chlorhexidine, povidone iodine and
      amphotericin B. Regimen 2 contained nystatin and povidone iodine. 70 patients
      (40.5%) received the first prophylaxis regimen, 89 patients (51.4%) received the
      second prophylaxis regimen and the remaining 14 patients (8.1%) were not
      adherence to the use of the mouthwashes and were excluded from the analysis.
      Results: OM was detected in 60.7% of patients with mean (SD) age of 38.1+/-14.6
      years. Multivariate analysis showed that only the female gender and the
      prophylactic regimen were the significant predictors of OM. Conclusion: We found
      that addition of amphotericin B and chlorhexidine, to the nystatin and povidone
      iodine resulted in a significant beneficial effect in prevention OM.

PMID- 30233778
TI  - Role of Hippo Pathway Effector Tafazzin Protein in Maintaining Stemness of
      Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSC).
AB  - Tafazzin (TAZ) protein has been upregulated in various types of human cancers,
      although the basis for elevation is uncertain, it has been made definite that the
      effect of mutation in the hippo pathway, particularly when it is switched off,
      considerably activates tafazzin transcriptionally and thus this results in tissue
      or tumor overgrowth. Recent perceptions into the activity of tafazzin, have
      ascribed to it, a role as stem cell factor in mouse mesenchymal and as well as in
      neural stem cells. Being a downstream molecule in Hippo signalling,
      phosphorylation or dephosphorylation of tafazzin gene regulates its
      transcriptional activity and the stemness of mesenchymal stem cells. Commonly,
      extracellular matrix controls the stem cell fate commitment and perhaps tafazzin
      controls stemness through altering the extra cellular matrix. Extracellular
      matrix is generally made up of prime proteoglycans and the fate stabilization of
      the resulting lineages is surveilled by engineering these glycans. Tafazzin
      degradation and addition of proteoglycans affect physical attributes of the
      extracellular matrix that drives cell differentiation into various lineages.
      Thus, tafazzin along with major glycans present in the extracellular matrix is
      involved in imparting stemness. However, there are incoherent molecular events,
      wherein both tafazzin and the extracellular matrix components, together either
      activate or inhibit differentiation of stem cells. This review discusses about
      the role of tafazzin oncoprotein as a stemness factor.

PMID- 30233779
TI  - Epigenetics of oral and oropharyngeal cancers.
AB  - Oral and oropharyngeal cancers represent the two most common malignancies of the
      head and neck region. The major risk factors for these cancers include alcohol
      consumption, tobacco use (via smoking or chewing) and high-risk human
      papillomavirus infection. The transition from normal epithelium to premalignant
      tissue and finally carcinoma is in part caused by a summation of genetic and
      epigenetic modifications. Epigenetic refers to modifications in the way the
      genome is expressed in cells. The most common examples of epigenetic control of
      gene expression are DNA methylation, histone modification and regulation by small
      non-coding RNAs. The aim of the current paper was to review the recent studies on
      the main epigenetic changes that have been suggested to serve a role in the
      carcinogenesis process and progression of oral and oropharyngeal cancers.
      Furthermore, it is discussed how the epigenetic changes may be used as potential
      predictive biomarkers and how recent findings in the field may impact the
      personalized cancer therapy approach for these tumors.

PMID- 30233780
TI  - ALDH1 as a prognostic marker for lymph node metastasis in OSCC.
AB  - Long-term survival in cases of head and neck squamous cell carcinoma,
      particularly oral squamous cell carcinoma (OSCC), remains a rare achievement in
      the field of clinical oncology. In recent years, the theory of cancer stem cells
      (CSCs) has emerged and been used to offer explanations for tumour recurrence and
      metastasis. The present aim was to investigate the role of aldehyde dehydrogenase
      1 (ALDH1) as a CSC-marker for OSCC and to determine the role of p16ink4a, which
      is also a surrogate marker of human papilloma virus (HPV), in the expression of
      ALDH1. The study cohort comprised of 186 surgically-treated cases of OSCC. The
      primaries were located in the oral cavity. The expression of the CSC marker
      (CSCM) ALDH1 was evaluated via immunohistochemistry (IHC) of a tissue microarray.
      HPV detection was performed by polymerase chain reaction and an HPV Array kit.
      Furthermore, the IHC expression of p16ink4a was also analysed. Risk regression
      models as the Kruskal Wallis test was used to assess the association of CSCM and
      p16ink4a expression with tumour size and lymph node metastasis, and cox
      proportional hazards were analysed. Additionally, coexpression of the markers
      ALDH1 and p16ink4a was analysed with regard to associations with tumour
      classification. Overall, high expression of ALDH1 in lymph nodes was
      significantly associated with Union for International Cancer Control (UICC) stage
      IV (P=0.044) and T4 stage cancer (P=0.03). p16ink4a positivity, in cases of HPV
      negativity, was associated with worse survival rate compared with that of the
      total cohort (P=0.048). Collectively the data indicate that ALDH1 expression may
      be suitable for detection of unfavourable prognosis in OSCC patients, based in
      part on its apparent role as a marker of metastasis. HPV status was not
      statistically predictive of patient outcome or CSCM expression; however, p16ink4a
      remains a potential marker in HNSCC Further in vitro studies with ALDH1 and
      p16ink4a should be performed to evaluate the expression of ALDH1 and HPV in cell
      culture and to clarify the role of ALDH1 as a marker for increased invasiveness
      of OSCC cells.

PMID- 30233781
TI  - Differential gene expression profiling of the sciatic nerve in type 1 and type 2
      diabetic mice.
AB  - Diabetic peripheral neuropathy (DPN) is a common complication of diabetes
      mellitus (DM). The pathogenic mechanisms of DPN and the therapeutic interventions
      required may be distinct between type 1 (T1) and type 2 (T2) DM. However, the
      molecular mechanisms underlying the pathogenesis of DPN in both types of diabetes
      remain unclear. The aim of the current study was to identify the changes in genes
      and pathways associated with DPN in sciatic nerves of T1- and T2DM mice using
      bioinformatics analysis. The microarray profiles of sciatic nerves of T1DM
      (GSE11343) and T2DM (GSE27382) mouse models were downloaded from the Gene
      Expression Omnibus database to identify differentially expressed genes (DEGs) in
      each. DEGs in the two types of DM (with fold change >=2 and P<0.05) were
      identified with BRB-ArrayTools. Gene Ontology (GO) term and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) pathway enrichment analyses were performed using the
      Database for Annotation, Visualization and Integrated Discovery. A protein
      protein interaction (PPI) network was constructed using the Search Tool for the
      Retrieval of Interacting Genes/Proteins and visualized using Cytoscape. Compared
      with control samples, 623 and 1,890 DEGs were identified in sciatic nerves of T1-
      and T2DM mice, respectively. Of these, 75 genes were coordinately dysregulated in
      the sciatic nerves of both models. Many DEGs unique to T1DM mice were localized
      to the nucleoplasm and were associated with regulation of transcription
      processes, while many unique to T2DM mice were localized at cell junctions and
      were associated with ion transport. In addition, certain DEGs may be associated
      with the different treatment strategies used for the two types of DM. This
      analysis provides insight into the functional gene sets and pathways operating in
      sciatic nerves in T1- and T2DM. The results should improve understanding of the
      molecular mechanisms underlying the pathophysiology of DPN, and provide
      information for the development of therapeutic strategies for DPN specific to
      each type of DM.

PMID- 30233782
TI  - Identification of genes and pathways in esophageal adenocarcinoma using
      bioinformatics analysis.
AB  - Esophageal adenocarcinoma (EAC) is one of the most common subtypes of esophageal
      cancer, and is associated with a low 5-year survival rate. The present study
      aimed to identify key genes and pathways associated with EAC using bioinformatics
      analysis. The gene expression profiles of GSE92396, which includes 12 EAC samples
      and 9 normal esophageal samples, were downloaded from the Gene Expression Omnibus
      database. Differentially expressed genes (DEGs) between the EAC and normal
      samples were identified using the limma package in R language. Gene ontology and
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the
      identified DEGs were conducted using the online analysis tool, the Database for
      Annotation, Visualization and Integrated Discovery. A protein-protein interaction
      (PPI) network of the DEGs was constructed using the Search Tool for the Retrieval
      of Interacting Genes (STRING) database and Cytoscape software. Finally, module
      analysis was conducted for the PPI network using the MCODE plug-in in Cytoscape.
      Of the 386 DEGs identified, the 150 upregulated genes were mainly enriched in the
      KEGG pathways of complement and coagulation cascades, maturity onset diabetes of
      the young and protein digestion and absorption; and the 236 downregulated genes
      were mainly enriched in amoebiasis, retinol metabolism and drug metabolism
      cytochrome P450. Based on information from the STRING database, a PPI network
      comprising of 369 nodes and 534 edges was constructed in Cytoscape. The top 10
      hub nodes with the highest degrees were determined as interleukin-8, involucrin,
      tissue inhibitor of metalloproteinase 1, fibronectin 1, serpin family E member 1,
      serpin family A member 1, cystic fibrosis transmembrane conductance regulator,
      secreted phosphoprotein 1, collagen type I alpha 1 chain and angiotensinogen. A
      total of 6 modules were detected from the PPI network that satisfied the criteria
      of MCODE score >4 and number of nodes >4. KEGG pathways enriched for the module
      DEGs were mainly within arachidonic acid metabolism, complement and coagulation
      cascades and rheumatoid arthritis. In conclusion, identification of these key
      genes and pathways may improve understanding of the mechanisms underlying the
      development of EAC, and may be used as diagnostic and therapeutic targets in EAC.

PMID- 30233783
TI  - In silico identification of lipid-binding alpha helices of uncoupling protein 1.
AB  - Uncoupling protein 1 (UCP1) located at the mitochondrial inner membrane serves an
      important role in adaptive non-shivering thermogenesis. Previous data has
      demonstrated that membrane lipids regulate the biological functions of membrane
      proteins. However, how mitochondrial lipids interact with UCP1 still remains
      elusive. In this study, the interactions between UCP1 and membrane lipids were
      investigated, using bioinformatic approaches due to the limitations associated
      with experimental techniques. A total of 8 UCP1 peptide regions with alpha
      helices were identified and related to functional sites of UCP1. These were all
      novel peptide sequences compared with the known protein-lipid interactions. Among
      several types of UCP1-binding molecules, cardiolipin appeared to serve as a key
      interacting molecule of the 8 lipid-binding alpha-helix regions of UCP1. Two
      cardiolipin-binding lysines (K175 and K269) of UCP1 may be crucial for this UCP1
      cardiolipin recognition and UCP1 function. The present findings provide novel
      insight into the associations of UCP1 with lipids and the potential drug targets
      in UCP1-associated diseases.

PMID- 30233784
TI  - Repression of IGF-I-induced osteoblast migration by (-)-epigallocatechin gallate
      through p44/p42 MAP kinase signaling.
AB  - Polyphenolic compounds in beverages may have benefits in the prevention of
      osteoporosis. It has been demonstrated previously that insulin-like growth factor
      I (IGF-I) could stimulate the migration of osteoblasts. In the present study, it
      was investigated whether chlorogenic acid, a major polyphenol in coffee, and (-)
      epigallocatechin gallate (EGCG), a major polyphenol in green tea, could affect
      this IGF-I-stimulated migration of osteoblast-like MC3T3-E1 cells. The IGF-I
      stimulated osteoblast migration, evaluated by Transwell cell migration and wound
      healing assays, was inhibited by EGCG but not chlorogenic acid. IGF-I induced the
      phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase, p70 S6 kinase
      and Akt. The IGF-I-induced migration was suppressed by PD98059, a MAP kinase
      kinase 1/2 inhibitor, and deguelin, an Akt inhibitor, but not rapamycin, an
      inhibitor of the upstream kinase of p70 S6 kinase (mammalian target of
      rapamycin). EGCG attenuated the IGF-I-induced phosphorylation of p44/p42 MAP
      kinase but not Akt. Taken together, the present results suggest that EGCG
      inhibits IGF-I-induced osteoblast migration via p44/p42 MAP kinase.

PMID- 30233785
TI  - Oxidant and antioxidant status in coronary artery disease.
AB  - Formation of atherosclerotic plaques is the major cause of coronary artery
      disease (CAD). Several lines of study have revealed the role of oxidative stress
      in CAD pathogenesis. In the present study the aim was to investigate the
      oxidative and antioxidative markers in CAD patients and a control population. The
      study sample comprised of acute coronary syndrome (ACS) patients, chronic CAD
      patients and healthy controls (n=30/group). Blood samples of patients and control
      subjects were collected to measure the concentrations of reduced glutathione
      (GSH), malondialdehyde (MDA) and the percentage of MDA release as well as the
      activity of erythrocyte glutathione peroxidase (GPx) and total antioxidant
      capacity (TAC) of plasma. All parameters were measured by spectrophotometric
      methods. Additionally, oxidant/antioxidant status was compared between CAD
      patients with single, double or triple-vessel stenosis and in comparison with
      controls. The results indicated a significant increase in MDA level and the
      percentage of MDA release (P<0.05), and a marked decrease in GSH concentration
      (P<0.0001), TAC (P<0.0001) and the activity of erythrocyte GPx (P<0.0001) in the
      patient groups compared controls. ACS patients exhibited a similar pattern of
      data when compared with the chronic CAD group. Similar results were also observed
      when chronic CAD patients with single, double or triple vessel stenosis and
      controls were compared. The present study indicates that the acute form of CAD is
      more susceptible to oxidative damage, suggesting that use of antioxidant therapy
      may be warranted to ameliorate oxidative stress in this condition.

PMID- 30233786
TI  - Serum ferritin is a candidate biomarker of disease aggravation in amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. The mechanism
      that defines the loss of neurons in ALS is still not clearly understood, and
      there is no effective therapy to block its progression. Previous studies indicate
      that a disorder of iron homeostasis exists in ALS and based on this, the change
      of serum iron and ferritin and the association between iron metabolism and
      clinical features in Chinese Han patients with ALS was further investigated in
      the present study, in order to define its pathogenesis. Two cohorts were
      established: An ALS group consisting of 24 patients and a control group
      consisting of 38 healthy volunteers. Venous blood samples were collected for
      serum iron and ferritin analysis. The results indicated that the levels of serum
      iron were significantly decreased in patients with ALS (P<0.05), while there was
      no significant difference in serum ferritin between the ALS and control groups.
      However, the levels of serum ferritin were increased significantly in ALS
      patients with bulbar-onset (vs. limb-onset in females), dysphagia (vs. without
      dysphagia), longer disease duration (>12 months vs. <=12 months in males) and
      lower ALS Functional Rating Scale-Revised score (<33 vs. >=33; P<0.05). These
      results suggested that there was dysregulation of iron metabolism in Chinese Han
      patients with ALS and that serum ferritin may be a candidate biomarker of
      aggravation in these patients.

PMID- 30233788
TI  - Preparation of Astragalus membranaceus lectin and evaluation of its biological
      function.
AB  - Astragalus membranaceus lectin (AML) was abstracted as a supposedly novel
      agglutinin of 67 kDa from the seeds of Astragalus membranaceus. The seeds of
      Astragalus membranaceus were treated with acetate, ammonium sulfate
      precipitation, and purified by HiTrap SP XL ion column and Superdex G25 gel
      filtration chromatography to obtain the AML. AML contained 16.4% sugar, ~70%
      polar amino acids and ~30% hydrophobic amino acids. The AML exhibited
      agglutination activity toward human and animal erythrocytes, particularly human
      blood type O and rabbit erythrocytes. It also exhibited acid/alkali resistance
      and thermal denaturation above 64 degrees C. Compared with human normal liver HL
      7702 cells, different concentrations of AML (6.25, 12.50, 25.00 and 50.00 ug/ml)
      exhibited superior inhibitory effects on the growth of SGC-7901, HepG2 and H22
      carcinoma cell lines, and displayed marked antibacterial effects on bacteria; the
      half maximal inhibitory concentration for B. dysenteriae, S. aureus and E. coli
      were 85.4, 80.2 and 65.3 ug/ml, respectively.

PMID- 30233787
TI  - Increased ratio of Th17 cells to SIGIRR+CD4+ T cells in peripheral blood of
      patients with SLE is associated with disease activity.
AB  - To investigate the clinical significance of the ratio of T helper cell 17 (Th17)
      cells to single immunoglobulin IL-1-related receptor (SIGIRR)+ cluster of
      differentiation (CD4)+ T cells in patients with systemic lupus erythematosus
      (SLE), novel data and data from previous studies were analyzed. The frequency of
      Th17 cells in peripheral blood mononuclear cells (PBMCs) and their correlation
      with clinical data were evaluated in 48 patients with SLE and 38 healthy controls
      through flow cytometry. Compared with healthy controls, the percentage of Th17
      cells was significantly increased in the PBMCs of patients with SLE (Z=-5.82,
      P<0.001). Compared with inactive SLE (ISLE), the percentage of Th17 cells in
      active SLE (ASLE) were significantly increased (Z=-4.26, P<0.0001). Compared with
      patients without lupus nephritis, the frequency of Th17 cells was significant
      increased (Z=-2.20, P=0.028). The frequency of Th17 cells was inversely
      correlated with the frequency of SIGIRR+CD4+ T cells (r=-0.61, P<0.001). The
      ratio of Th17 cells to SIGIRR+CD4+ T cells in ASLE was significantly increased
      compared with healthy controls or patients with ISLE (P<0.001) and was inversely
      correlated with complement component 3 and complement component 4, and positively
      correlated with SLE disease activity index and 24-h proteinuria (P<0.05). In
      summary, increased numbers of Th17 cells and decreased numbers of SIGIRR+CD4+ T
      cells in patients with SLE suggested that SIGIRR+CD4+ T and Th17 cells may be
      involved in the pathogenesis of SLE.

PMID- 30233790
TI  - Oxidative stress induced by portal vein embolization in fatty liver: Experimental
      study of a nonalcoholic steatohepatitis model.
AB  - The present study aimed to investigate whether excessive oxidative stress
      production or reduction of antioxidative stress potential may occur following
      portal vein embolization (PVE) in an experimental animal nonalcoholic
      steatohepatitis (NASH) model. A NASH rabbit model (n=11) was established by
      feeding of a fat diet for 4 weeks, and a normal diet rabbit model (n=11) was
      prepared as a control. The oxidative status of NASH was examined by measuring
      derivatives of reactive oxygen metabolites (d-ROM) for oxidative stress and
      biological antioxidative potential (BAP) for antioxidative potential in the NASH
      model and normal group. Additionally, oxidative status of PVE after 2 weeks was
      assessed by measuring d-ROM and BAP in the NASH and normal liver models.
      Oxidative status in a PVE+NASH model was also detected. In the process of NASH
      creation (fat diet for 4 weeks), total cholesterol was increased in the NASH
      group (P<0.0001). In the NASH group, PVE induced an increase in serum aspartate
      transaminase (P=0.0318). At 4 weeks after initiation of the fat diet, a decrease
      in BAP was determined as statistically significant (P<0.0001). In normal liver, d
      ROM production was stimulated in the Sham group after 2 weeks (P=0.0152), but BAP
      was not altered (P=0.6119). In NASH liver, d-ROM production was stimulated in PVE
      and Sham groups (P<0.0001 and P=0.0189, respectively), but BAP did not change
      (P>0.05). In conclusion, decrease of antioxidant potential may promote NASH
      progression. Additionally, PVE appeared to cause a surge in oxidative stress in
      NASH liver.

PMID- 30233789
TI  - VDR and TNFSF11 polymorphisms are associated with osteoporosis in Thai patients.
AB  - Determining molecular markers for osteoporosis may be valuable for improving the
      quality of life of affected elderly patients by aiding in early detection and
      disease management. In the present study, the association between single
      nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and tumour
      necrosis factor superfamily number 11 (TNFSF11) genes and the susceptibility of
      developing osteoporosis was investigated in a Thai female cohort. The study group
      consisted of 105 Thai postmenopausal patients diagnosed with osteoporosis and 132
      healthy Thai postmenopausal female volunteers. DNA extracted from blood samples
      was used to genotype the VDR and TNFSF11 genes using polymerase chain reaction
      restriction fragment length polymorphism and sequencing analysis. For VDR, the
      frequencies of the genotypes TT, CT and CC for the TaqI SNP (rs731236) were
      87.88, 11.36 and 0.76%, respectively, in the control group, while in the
      osteoporosis cohort were 92.38, 5.71 and 1.91%, respectively. For the FokI SNP
      (rs2228570), the frequencies of the genotypes CC, CT and TT were 31.06, 55.30 and
      13.64%, respectively, in the control group, and in the osteoporosis group were
      29.52, 43.81 and 26.67%, respectively. For BsmI SNP (rs1544410), the frequencies
      of the genotypes GG, GA and AA were 78.03, 18.94 and 3.03%, respectively, in
      control group, and in the osteoporosis group were 80.95, 18.10 and 0.95%,
      respectively. The significant risk of osteoporosis associated with the FokI SNP
      was determined. The odds ratio (95% confidence interval) was 2.30 (1.14-4.69;
      P=0.01) among patients with osteoporosis with TT as the susceptibility genotype.
      For TNFSF11, the frequencies of the genotypes TT, CT and CC for the -290C>T SNP
      (rs9525641) in the control group were 36.36, 50.76 and 12.88%, respectively,
      while in the osteoporosis group were 31.43, 56.19 and 12.38%, respectively. For
      the -643C>T SNP (rs9533156), the frequencies of the genotypes TT, CT and CC in
      the control group were 35.61, 48.48 and 15.91%, respectively, while in the
      osteoporosis group were 32.38, 55.24 and 12.38%, respectively. For the -693G>C
      SNP (rs9533155), the frequencies of the genotypes CC, CG, and GG in the control
      group were 39.39, 46.97 and 13.64%, respectively, and in the osteoporosis group
      were 36.19, 53.33 and 10.48%, respectively. No significant associations of the
      TNFSF11 SNPs with osteoporosis were determined; however, it was notable that the
      GCT haplotype of TNFSF11 may be a protective haplotype for osteoporosis.
      Therefore, it was concluded that the SNP FokI of VDR may be a potential molecular
      biomarker for the development of osteoporosis in Thai females.

PMID- 30233792
TI  - Neutrophil-to-lymphocyte ratio as a predictor of postoperative morbidity in
      patients with distal cholangiocarcinoma.
AB  - Systemic inflammatory-, immunological- and nutritional-based indices, such as the
      neutrophil-to-lymphocyte ratio (NLR), the prognostic nutritional index (PNI) and
      the Glasgow prognostic score (GPS), are drawing considerable research attention
      to predict the long-term prognosis of many types of cancer. Recently, these
      parameters have also been reported to be useful in predicting postoperative
      morbidity in several fields, including colorectal and otolaryngological cancer.
      However, while distal cholangiocarcinoma exhibits a high morbidity rate, its risk
      factors of morbidity have not yet been established. This is because previous
      studies have analyzed distal cholangiocarcinoma as periampullary tumors combined
      with pancreatic head cancer. Therefore, the aim of the present study was to
      investigate the application of the NLR, the PNI and the GPS in evaluating risk
      factors for postoperative morbidity in patients with distal cholangiocellular or
      ampullary carcinoma. Eighty-four patients who underwent pancreaticoduodenectomy
      (PD) for distal cholangiocellular or ampullary carcinoma at the Department of
      Surgery in Kitasato University Hospital between 2008 and 2016 were enrolled.
      Associations between perioperative characteristics (NLR, PNI and GPS) and
      postoperative complications (Clavien-Dindo classification grade III or higher)
      were retrospectively analyzed. In the univariate analysis, neutrophil and
      lymphocyte counts, body mass index (BMI) and the NLR were associated with
      postoperative complications (P<0.05). In the multivariate analysis, BMI [>23.0
      kg/m2; odds ratio (OR): 3.80, 95.0% confidence interval (CI): 1.35-11.83;
      P=0.011] and the NLR (>2.0; OR: 6.77, 95.0% CI: 2.44-21.13; P<0.001) were
      independent risk factors for postoperative complications. BMI and the NLR are
      valuable predictors of postoperative morbidity following PD in patients with
      distal cholangiocarcinoma. It would be beneficial to determine treatment
      strategies for distal cholangiocarcinoma based on the NLR to reduce postoperative
      complications.

PMID- 30233791
TI  - The role of automated cytometry in the new era of cancer immunotherapy.
AB  - The introduction in the clinical practice of several new approaches to cancer
      immunotherapy has greatly increased the interest in analytical methodologies that
      can define the immunological profile of patients in the clinical setting. This
      requires huge effort to obtain reliable monitoring tools that could be used to
      improve the patient's clinical outcome. The clinical applications of flow
      cytometry (FCM) in oncology started with the measurement of DNA content for the
      evaluation of both ploidy and cell cycle profile as potential prognostic
      parameters in the majority of human solid cancer types. The availability of
      monoclonal antibodies widely broadened the spectrum of clinical applications of
      this technique, which rapidly became a fundamental tool for the diagnosis and
      prognosis of malignant hematological diseases. Among the emerging clinical
      applications of FCM, the study of minimal residual disease in hematological
      malignancies, the quantification of blood dendritic cells in various types of
      tumors, the study of metastatic spread in solid tumors throughout both the
      analysis of circulating endothelial progenitor cells and the identification and
      characterization of circulating tumor cells, all appear very promising. More
      recently, an advanced single cell analysis technique has been developed that
      combines the precision of mass spectrometry with the unique advantages of FCM.
      This approach, termed mass cytometry, utilizes antibodies conjugated to heavy
      metal ions for the analysis of cellular proteins by a mass spectrometer. It
      provides measurement of over 100 simultaneous cellular parameters in a single
      sample and has evolved from a promising technology to a high recognized platform
      for multi-dimensional single-cell analysis. Should a careful standardization of
      the analytical procedures be reached, both FCM and mass cytometry could
      effectively become ideal tools for the optimization of new immunotherapeutic
      approaches in cancer patients.

PMID- 30233793
TI  - Perforated gastrointestinal stromal tumor in the small intestine: A rare case of
      Torricelli-Bernoulli sign.
AB  - The Torricelli-Bernoulli sign is a computed tomography (CT) finding that occurs
      when ulceration/necrosis of a submucosal gastrointestinal tumor releases a stream
      of air bubbles into the intestinal lumen. A 75-year-old man developed acute
      abdominal pain at night and presented to a local doctor. Acute abdomen was
      diagnosed and he was referred to the Emergency Department at Tokai University
      Oiso Hospital. On CT scans, disseminated intestinal tumor-like lesions were seen
      in the right lower abdomen. The Torricelli-Bernoulli sign and free intraabdominal
      gas were observed, so perforation of an intestinal tumor was diagnosed and
      emergency surgery was performed. At operation, there was scanty opaque ascites in
      the right lower abdomen and an ileal tumor associated with nodules that suggested
      peritoneal dissemination. Partial resection of the ileum was performed and
      peritoneal lavage was conducted. The patient was discharged on postoperative day
      11. Histopathological examination revealed a high risk gastrointestinal stromal
      tumor. The abdominal nodules were metastases, indicating that the tumor was Stage
      IV. The patient is currently on treatment with an oral tyrosine kinase inhibitor
      (imatinib).

PMID- 30233795
TI  - Radiation-induced glioblastoma with rhabdoid characteristics following treatment
      for medulloblastoma: A case report and review of the literature.
AB  - Glioblastoma multiforme (GBM) is a high-grade glioma that may develop from
      several other central nervous system tumors after radiation therapy. We herein
      report a case of GBM occurring 8 years after radiation therapy for
      medulloblastoma. The secondary tumor was histologically distinctly different from
      the primary tumor. Previously reported cases indicate that GBM induced by
      radiation therapy is associated with a highly aggressive clinical course with a
      high risk of early recurrence and poor prognosis. In addition, histological
      examination revealed that the tumor cells exhibited characteristics of both GBM
      and rhabdoid tumor cells. The diverse pathological characteristics of GBM may
      reflect the potential effects of radiation therapy on the tumor.

PMID- 30233794
TI  - Evaluation of inflammation-based markers for predicting the prognosis of
      unresectable pancreatic ductal adenocarcinoma treated with chemotherapy.
AB  - Predicting the prognosis of unresectable pancreatic ductal adenocarcinoma (PDAC)
      is useful in determining the appropriate management strategy. The present study
      aimed to investigate the association between PDAC prognosis and inflammation
      based markers, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to
      lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score
      (mGPS) and controlling nutritional status score. A total of 72 patients with
      unresectable PDAC who received chemotherapy were included. Inflammation-based
      markers were measured prior to treatment. The median progression-free survival
      (PFS) and overall survival (OS) were 117 days (range, 10-781 days) and 244 days
      (range 43-781 days), respectively. The cut-off value of continuous variables that
      predicted the median OS (244 days) was calcualted. Univariate analysis of PFS
      showed that disease stage, first-line chemotherapy regimen, carcinoembryonic
      antigen (CEA), NLR, platelet-to-lymphocyte ratio (PLR), mGPS and controlling
      nutritional status (CONUT) scores were associated with PFS. Among them, stage,
      first-line chemotherapy regimen, CEA, NLR and mGPS were independent prognostic
      factors for PFS in multivariate analysis. Univariate analysis of OS showed that
      stage, first-line chemotherapy regimen, CA19-9, NLR, PLR, prognostic nutritional
      index (PNI), mGPS and CONUT score were associated wtih OS. Among them, first-line
      chemotherapy and mGPS were independent prognostic factors for OS according to
      multivariate analysis. Univariate and multivariate analyses revealed that a NLR
      >=4.0 and mGPS 2 were independent prognostic factors for PFS. For OS, mGPS 2 was
      an independent prognostic factor. In conclusion, mGPS was the most useful marker
      in predicting the prognosis of patients with unresectable PDAC who received
      chemotherapy.

PMID- 30233796
TI  - Red nodular melanoma of the penile foreskin: A case report and literature review.
AB  - The penis is an extremely rare primary site for malignant melanomas, and the
      clinical presentation may vary greatly. We herein present the case of a 71-year
      old male patient who presented with a 6-year history of two slow growing,
      asymptomatic red macules on the penile foreskin. On physical examination, the
      mobility of the foreskin was good, and there was no metastasis on computed
      tomography and magnetic resonance imaging. The patient underwent segmental
      circumcision for treatment and histological diagnosis, and the histological
      examination revealed a malignant melanoma. As cancer cells were identified at the
      edge of the tissue specimen and computed tomography-positron emission tomography
      revealed increased uptake of 18F-fluorodeoxyglucose in the penis, wider resection
      and a right sentinel lymph node biopsy were performed; both specimens came back
      negative. Two years after the surgery, there has been no evidence of locoregional
      recurrence or distant metastases. The aim of this report is to alert physicians
      to include melanoma in the differential diagnosis of red-pigmented lesions of the
      penile foreskin.

PMID- 30233797
TI  - Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio and
      platelet-to-lymphocyte ratio in patients with glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive primary brain
      tumour in adults. Identification of accessible and cost-effective prognostic
      factors may better guide adjuvant treatment-related decisions. The neutrophil-to
      lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of host
      inflammatory response, and their increase has recently been shown to be a poor
      prognostic factor in several malignancies. The aim of the present study was to
      investigate the prognostic value of preoperative NLR and PLR in GBM patients.
      Between 2012 and 2017, 104 patients who had undergone surgery for GBM were
      considered for adjuvant therapy in our institution. Of those, 80 patients with
      evaluable pre-corticosteroid full blood count results were identified and
      included in the final analysis. The Eastern Cooperative Oncology Group
      performance status, localization, radiochemotherapy and second-line systemic
      therapy were found to be independent prognostic indicators for progression-free
      and overall survival. The median overall survival was 13.2 months. Patients with
      NLR <4 had a better median overall survival of 10.7 vs. 7.8 months in patients
      with NLR >4; however, this difference was not statistically significant (P>0.05).
      Overall survival also did not differ significantly between patients with low and
      those with high PLR values (10.2 vs. 15.2 months, respectively; P=0.105). In
      conclusion, the results of the present study suggest that pre-treatment NLR and
      PLR do not have prognostic value in GBM patients; however, large-scale trials are
      required to confirm these findings.

PMID- 30233799
TI  - Intra-articular synovial sarcoma in the ankle joint: A case report.
AB  - Intra-articular primary soft tissue sarcomas are extremely rare. The present case
      report describes a case of intra-articular synovial sarcoma of the ankle joint. A
      51-year-old man presented with complaints of swelling and progressive pain in the
      right ankle. Lateral radiographs of the ankle revealed lytic invasion of the
      anterior and posterior parts of the talus. Computed tomography imaging revealed a
      low-density lesion with calcifications around the ankle joint. Magnetic resonance
      imaging revealed that the diffuse lesion was isointense on T1-weighted images and
      hypointense to hyperintense on T2-weighted images. The final diagnosis was
      synovial sarcoma. The foot could not be salvaged as the sarcoma was diffusely
      spread throughout the ankle joint; thus, the patient underwent below-the-knee
      amputation with neoadjuvant and adjuvant chemotherapy. He succumbed from fatal
      arrhythmia 2 years following the initial diagnosis. Although intra-articular
      primary soft tissue sarcomas are extremely rare, the possibility of malignancy
      should be considered.

PMID- 30233798
TI  - Diagnoses of suspected cancer in otolaryngology practices in Germany.
AB  - The aim of this study was to estimate the prevalence of suspected head and neck
      cancer (HNC) diagnoses made by otolaryngologists in a population with
      subsequently confirmed cancer diagnoses in Germany. This study included patients
      with an initial documentation of confirmed cancer diagnosis made in 137
      otolaryngology practices between January 2012 and December 2016 (index date). The
      main outcome of the study was the prevalence of diagnoses of suspected cancer in
      otolaryngology practices within one year prior to the first documentation of a
      confirmed cancer diagnosis. The association between the defined demographic and
      clinical variables with diagnoses of suspected cancer was analyzed using a
      logistic regression model. A total of 6,446 patients received a confirmed cancer
      diagnosis. A total of 23.1% of the population received a diagnosis of suspected
      cancer within 12 months prior to the first documentation of a confirmed cancer
      diagnosis. Patients over the age of 50 (ORs ranging from 1.44 to 1.55) and men
      (OR=1.52) were more likely to receive a diagnosis of suspected cancer compared
      with patients aged 50 or under and women. Cancer of the pyriform sinus (OR=3.00)
      and cancer of the thyroid gland (OR=0.27) were associated with increased and
      decreased odds of a diagnosis of suspected cancer compared to laryngeal cancer
      respectively. Overall, approximately 23% of individuals received a diagnosis of
      suspected cancer within a year prior to the first documentation of confirmed HNC.

PMID- 30233800
TI  - High promoter activity of cytokeratin-19 gene in cholangiocarcinoma.
AB  - Conditionally replicating adenoviral vectors constructed with tumor-specific
      promoters (TSPs) offers a viable tool for the treatment of cholangiocarcinoma.
      The aim of the present study was to investigate cholangiocarcinoma-specific TSPs
      that remain active in adenoviral constructs in gene therapy. The mRNA expressions
      of cyclooxygenase-2, cytokeratin-19 (CK19), mucin-1, midkine and telomerase
      reverse transcriptase were determined in human cholangiocarcinoma cell lines,
      primary human hepatocytes and cholangiocytes using reverse transcription
      quantitative polymerase chain reaction. The candidate promoters constructed in
      adenoviral vectors were analyzed for their activities in cholangiocarcinoma cell
      lines, primary human hepatocytes and cholangiocytes using dual-luciferase
      reporter assays. The mRNA expression of CK19 was markedly higher in the QBC939
      cell line, indicating specificity to cholangiocarcinoma. Moreover, the promoter
      activity of CK19 in the adenoviral vector in infected cholangiocarcinoma cells
      was found to be significantly stronger compared with that in infected primary
      human hepatocytes and cholangiocytes. CK19 may be implicated in the pathogenesis
      of cholangiocarcinoma, as demonstrated by the stronger activity of its promoter,
      as well as the higher expression of mRNA in tumor cells. Therefore, the use of
      the promoter sequence of the CK19 gene may represent a potential tool in
      cholangiocarcinoma-specific adenoviral gene therapy.

PMID- 30233801
TI  - Metabolomics of World Trade Center-Lung Injury: a machine learning approach.
AB  - Introduction: Biomarkers of metabolic syndrome expressed soon after World Trade
      Center (WTC) exposure predict development of WTC Lung Injury (WTC-LI). The
      metabolome remains an untapped resource with potential to comprehensively
      characterise many aspects of WTC-LI. This case-control study identified a
      clinically relevant, robust subset of metabolic contributors of WTC-LI through
      comprehensive high-dimensional metabolic profiling and integration of machine
      learning techniques. Methods: Never-smoking, male, WTC-exposed firefighters with
      normal pre-9/11 lung function were segregated by post-9/11 lung function. Cases
      of WTC-LI (forced expiratory volume in 1s <lower limit of normal, n=15) and
      controls (n=15) were identified from previous cohorts. The metabolome of serum
      drawn within 6 months of 9/11 was quantified. Machine learning was used for
      dimension reduction to identify metabolites associated with WTC-LI. Results: 580
      metabolites qualified for random forests (RF) analysis to identify a refined
      metabolite profile that yielded maximal class separation. RF of the refined
      profile correctly classified subjects with a 93.3% estimated success rate. 5
      clusters of metabolites emerged within the refined profile. Prominent subpathways
      include known mediators of lung disease such as sphingolipids (elevated in cases
      of WTC-LI), and branched-chain amino acids (reduced in cases of WTC-LI).
      Principal component analysis of the refined profile explained 68.3% of variance
      in five components, demonstrating class separation. Conclusion: Analysis of the
      metabolome of WTC-exposed 9/11 rescue workers has identified biologically
      plausible pathways associated with loss of lung function. Since metabolites are
      proximal markers of disease processes, metabolites could capture the complexity
      of past exposures and better inform treatment. These pathways warrant further
      mechanistic research.

PMID- 30233802
TI  - Pirfenidone in patients with unclassifiable progressive fibrosing interstitial
      lung disease: design of a double-blind, randomised, placebo-controlled phase II
      trial.
AB  - Introduction: Despite extensive multidisciplinary team (MDT) assessment, some
      patients have interstitial lung disease (ILD) that is considered unclassifiable
      (uILD), for which there are currently no approved treatments. This study will
      assess the efficacy and safety of the antifibrotic pirfenidone in treating uILD.
      Methods and analysis: This double-blind, randomised, placebo-controlled phase II
      trial is enrolling adults with fibrosing ILD, including uILD that fulfils
      proposed research criteria for interstitial pneumonia with autoimmune features
      (IPAF), that cannot be classified with moderate or high confidence to any
      category of ILD following MDT discussion. Study participants must have >10%
      fibrosis on high-resolution CT scan within the previous 12 months, forced vital
      capacity (FVC) >=45% and diffusing capacity of the lung for carbon monoxide >=30%
      of predicted values. Study participants will be randomised to receive 801 mg
      pirfenidone or placebo three times daily for 24 weeks. The efficacy of
      pirfenidone vs placebo will be assessed by daily measurement of FVC using a
      handheld spirometer over the treatment period. Other functional parameters,
      patient-reported outcomes, samples for biomarker analysis and safety endpoints
      will be collected. Additionally, the study will assess the efficacy and safety of
      pirfenidone with and without concomitant mycophenolate mofetil treatment and in
      study participants with or without IPAF. Ethics and dissemination: This trial is
      being conducted in accordance with the International Conference on Harmonisation
      E6 guideline for Good Clinical Practice, Declaration of Helsinki and local laws
      for countries in which the research is conducted. Trial registration number:
      NCT03099187.

PMID- 30233803
TI  - Elevated serum adiponectin and tumor necrosis factor-alpha and decreased
      transthyretin in Japanese elderly women with low grip strength and preserved
      muscle mass and insulin sensitivity.
AB  - Objective: To determine if adiponectin levels are associated with low grip
      strength among the elderly independently of insulin resistance and inflammation.
      Research design and methods: Cross-sectional associations were analyzed by
      logistic regression between low grip strength and body composition, elevated
      serum adiponectin (>=20 mg/L), and biomarkers of nutritious stasis, insulin
      resistance and inflammation in 179 community-living Japanese women. Sarcopenia
      was evaluated using the Asian criteria. Results: No women had sarcopenia. In
      bivariate analyses, low grip strength (n=68) was positively associated with age,
      log tumor necrosis factor-alpha (TNF-alpha) and hyperadiponectinemia (n=37) and
      inversely with body weight, height, skeletal muscle mass, serum albumin,
      transthyretin (TTR), fat mass, serum zinc and hemoglobin (all p<0.01). In a fully
      adjusted model, TTR (0.90: 0.83-0.98, p=0.01) in addition to age (p=0.007),
      height (p=0.004) and skeletal muscle mass (p=0.008) emerged as independent
      determinants of low grip strength. When TTR was removed from the full model, TNF
      alpha was associated with low grip strength (7.7; 1.3-45.8, p=0.02). Mean waist
      circumference and high-density lipoprotein cholesterol did not differ between
      women with and without low grip strength and were within the respective normal
      range. Women with hyperadiponectinemia had higher percentage of women with low
      grip strength and lower grip strength (both p<0.01). Conclusions:
      Hyperadiponectinemia and elevated TNF-alpha in addition to decreased TTR, a
      biomarker of age-related catabolic states, were found in community-living
      Japanese elderly women with low grip strength and preserved muscle mass and
      insulin sensitivity.

PMID- 30233804
TI  - Hepatic fat and glucose tolerance in women with recent gestational diabetes.
AB  - Objective: Women with a history of gestational diabetes mellitus (GDM) have an
      elevated risk of ultimately developing pre-diabetes and diabetes later in life.
      They also have an increased prevalence of fatty liver, but recent studies have
      reported conflicting findings on whether hepatic fat affects their risk of pre
      diabetes/diabetes. Thus, we sought to evaluate the associations of liver fat with
      glucose homeostasis and determinants thereof in women with and without recent
      gestational dysglycemia. Methods: Two hundred and fifty-seven women underwent an
      antepartum oral glucose tolerance test (OGTT), which diagnosed 97 with GDM, 40
      with gestational impaired glucose tolerance (GIGT), and 120 with normal glucose
      tolerance (NGT). At a mean of 4.8 years post partum, they underwent an OGTT
      (which revealed that 52 had progressed to pre-diabetes/diabetes) and hepatic
      ultrasound, on which liver fat was graded as none (n=164), mild (n=66), or
      moderate (n=27). Results: Liver fat was more prevalent in women with previous GDM
      than in those with GIGT or NGT (p=0.009) and in women with current pre
      diabetes/diabetes than in those without (p=0.0003). As the severity of liver fat
      increased, there was a progressive worsening of insulin sensitivity and beta-cell
      function, coupled with rising fasting and 2-hour glucose (all p<0.0001). On
      multiple linear regression analyses, moderate liver fat was independently
      associated with lower insulin sensitivity (p=0.0002) and higher 2-hour glucose
      (p=0.009). Moreover, moderate liver fat emerged as an independent predictor of
      pre-diabetes/diabetes (OR=3.66, 95% CI 1.1 to 12.5). Conclusion: The higher
      prevalence of liver fat in women with previous GDM is associated with their
      increased risk of pre-diabetes/diabetes.

PMID- 30233805
TI  - Patterns and correlates of use of evidence-based interventions to control
      diabetes by local health departments across the USA.
AB  - Objective: The nearly 3000 local health departments (LHDs) nationwide are the
      front line of public health and are positioned to implement evidence-based
      interventions (EBIs) for diabetes control. Yet little is currently known about
      use of diabetes-related EBIs among LHDs. This study used a national online survey
      to determine the patterns and correlates of the Centers for Disease Control and
      Prevention Community Guide-recommended EBIs for diabetes control in LHDs.
      Research design and methods: A cross-sectional study was conducted to survey a
      stratified random sample of LHDs regarding department characteristics, respondent
      characteristics, evidence-based decision making within the LHD, and delivery of
      EBIs (directly or in collaboration) within five categories (diabetes-related,
      nutrition, physical activity, obesity, and tobacco). Associations between
      delivering EBIs and respondent and LHD characteristics and evidence-based
      decision making were explored using logistic regression models. Results: Among
      240 LHDs there was considerable variation among the EBIs delivered. Diabetes
      prevalence in the state was positively associated with offering the Diabetes
      Prevention Program (OR=1.28 (95% CI 1.02 to 1.62)), diabetes self-management
      education (OR=1.32 (95% CI 1.04 to 1.67)), and identifying patients and
      determining treatment (OR=1.27 (95% CI 1.05 to 1.54)). Although all
      organizational supports for evidence-based decision making factors were related
      in a positive direction, the only significant association was between evaluation
      capacity and identifying patients with diabetes and determining effective
      treatment (OR=1.54 (95% CI 1.08 to 2.19)). Conclusion: Supporting evidence-based
      decision making and increasing the implementation of these EBIs by more LHDs can
      help control diabetes nationwide.

PMID- 30233806
TI  - Serum albumin at 1 year predicts long-term renal outcome in lupus nephritis.
AB  - Objectives: The study aimed to determine if serum albumin at 12 months predicts
      long-term renal outcome at 48 months. Data from the NYU SAMPLE (Specimen and
      Matched Phenotype Linked Evaluation) Lupus Registry were used to compare the
      performance of albumin, anti-double-stranded DNA, C3/C4, proteinuria and
      haematuria. Methods: 82 patients with SLE with data at time of renal biopsy, at
      12 months and at a second visit, and up to 48 months were included. The
      significance of each biomarker as a predictor of an adverse renal outcome (ARO),
      defined as doubling of serum creatinine, as creatinine >4 mg/dL if initial >2.5
      mg/dL or ESRD, was evaluated in univariate and exploratory multivariable Cox
      proportional hazards models. Hazard ratios (HRs) for ARO with 95% CIs were
      generated. The receiver operating characteristic (ROC) curves at 48 months were
      used to identify the optimal cut-off point for albumin and proteinuria to predict
      ARO. Sensitivity, specificity, positive predictive value (PPV) and negative
      predictive value (NPV) were calculated for albumin and proteinuria. Results:
      Serum albumin and proteinuria had statistically significant HRs for ARO (0.140
      and 1.459, respectively). The model with both albumin and proteinuria indicated
      no additional independent contribution of proteinuria to albumin alone. The ROC
      curves identified cut-offs of 3.7 g/dL for albumin and 0.964 urine protein to
      creatinine ratio for proteinuria. Albumin had a sensitivity of 94%, specificity
      of 87%, PPV of 64% and NPV of 98%. Conclusions: This study demonstrates serum
      albumin >3.7 g/dL is a predictor of a favourable long-term renal outcome. These
      results support the inclusion of albumin as an outcome in lupus nephritis trials
      and treat-to-target guidelines.

PMID- 30233807
TI  - Discharge of patients with an acute upper gastrointestinal bleed from the
      emergency department using an extended Glasgow-Blatchford Score.
AB  - Objective: To use an extended Glasgow-Blatchford Score (GBS) cut-off of <=1 to
      aid discharge of patients presenting with acute upper gastrointestinal bleeding
      (AUGIB) from emergency departments. Background: The GBS accurately predicts the
      need for intervention and death in AUGIB, and a cut-off of 0 is recommended to
      identify patients for discharge without endoscopy. However, this cut-off is
      limited by identifying a low percentage of low-risk patients. Extension of the
      cut-off to <=1 or <=2 has been proposed to increase this proportion, but there is
      controversy as to the optimal cut-off and little data on performance in routine
      clinical practice. Methods: Dual-centre study in which patients with AUGIB and
      GBS <=1 were discharged from the emergency department without endoscopy unless
      there was another reason for admission. Retrospective analysis of associated
      adverse outcome defined as a 30-day combined endpoint of blood transfusion,
      intervention or death. Results: 569 patients presented with AUGIB from 2015 to
      2018. 146 (25.7%) had a GBS <=1 (70, GBS=0; 76, GBS=1). Of these, 103 (70.5%)
      were managed as outpatients, and none had an adverse outcome. GBS <=1 had a
      negative predictive value=100% and the GBS had an area under receiver operator
      characteristic (AUROC)=0.89 (95% CI 0.86 to 0.91) in predicting adverse outcomes.
      In 2008-2009, prior to risk scoring (n=432), 6.5% of patients presenting with
      AUGIB were discharged safely from the emergency department in comparison with
      18.1% (p<0.001) in this cohort. A GBS cut-off <=2 was associated with an adverse
      outcome in 8% of cases. Conclusion: GBS of <=1 is the optimal cut-off for the
      discharge of patients with an AUGIB from the emergency department.

PMID- 30233808
TI  - Exercise performance after salbutamol inhalation in non-asthmatic, non-athlete
      individuals: a randomised, controlled, cross-over trial.
AB  - Background: Asthma is a frequent diagnosis in competitive sports, and inhaled
      beta2-agonists are commonly used by athletes. Although inhaled beta2-agonists do
      not seem to improve performance in athletes, it has remained uncertain whether
      they can increase exercise performance in non-athletes. Objective: To investigate
      the effect of inhaled beta2-agonists on exercise performance in healthy non
      athlete individuals. Methods: In a double-blinded, placebo-controlled, cross-over
      trial, healthy, non-asthmatic, non-athlete individuals were randomised to
      inhalation of either 900 ug of salbutamol or placebo. Cardiopulmonary exercise
      testing, dynamic spirometry and impulse oscillometry were performed. The primary
      outcome was the effect from salbutamol on peak oxygen uptake, whereas secondary
      outcomes were breathing reserve and ventilation efficiency, and workload, heart
      rate, breath rate and minute ventilation at peak exercise under influence of
      salbutamol. Results: A total of 36 healthy subjects with a mean age of 26+/-5
      years were included. Salbutamol had no effect on peak oxygen uptake compared with
      placebo, 46.8+/-1.3 mL/kg/min versus 46.6+/-1.2 mL/kg/min, p=0.64. Salbutamol had
      no effect on workload, p=0.20, heart rate, p=0.23, breath rate, p=0.10, or minute
      ventilation, p=0.26, at peak exercise compared with placebo. Salbutamol lowered
      oxygen uptake, p=0.04, and workload, p=0.04, at anaerobic threshold compared with
      placebo. Forced expiratory volume in 1 s, 116%+/-13% of predicted, and peak
      expiratory flow, 122%+/-16% of predicted, increased after inhalation of
      salbutamol compared with placebo; 109%+/-13% and 117%+/-17%, respectively,
      p<0.01. Breathing reserve was found to be higher, 22%+/-2%, after salbutamol
      inhalation than after placebo, 16%+/-2%, p<0.01. Conclusion: Inhaled salbutamol
      did not improve peak oxygen uptake in healthy, non-asthmatic, non-athlete
      individuals compared with placebo. Trial registration number: NCT02914652.

PMID- 30233809
TI  - 'Take a Mental Break!' study: Role of mental aspects in running-related injuries
      using a randomised controlled trial.
AB  - Background: Running-related injuries (RRIs) can be considered the primary enemy
      of runners. Most literature on injury prediction and prevention overlooks the
      mental aspects of overtraining and under-recovery, despite their potential role
      in injury prediction and prevention. Consequently, knowledge on the role of
      mental aspects in RRIs is lacking. Objective: To investigate mental aspects of
      overtraining and under-recovery by means of an online injury prevention
      programme. Methods and analysis: The 'Take a Mental Break!' study is a randomised
      controlled trial with a 12 month follow-up. After completing a web-based baseline
      survey, half and full marathon runners were randomly assigned to the intervention
      group or the control group. Participants of the intervention group obtained
      access to an online injury prevention programme, consisting of a running-related
      smartphone application. This app provided the participants of the intervention
      group with information on how to prevent overtraining and RRIs with special
      attention to mental aspects. The primary outcome measure is any self-reported RRI
      over the past 12 months. Secondary outcome measures include vigour, fatigue,
      sleep and perceived running performance. Regression analysis will be conducted to
      investigate whether the injury prevention programme has led to a lower prevalence
      of RRIs, better health and improved perceived running performance. Ethics and
      dissemination: The Medical Ethics Committee of the University Medical Center
      Utrecht, the Netherlands, has exempted the current study from ethical approval
      (reference number: NL64342.041.17). Results of the study will be communicated
      through scientific articles in peer-reviewed journals, scientific reports and
      presentations on scientific conferences.

PMID- 30233810
TI  - Heading in soccer increases serum neurofilament light protein and SCAT3 symptom
      metrics.
AB  - Objectives: To determine the effect of heading a soccer ball on serum
      neurofilament light (NF-L) protein, plasma tau protein and symptom metrics
      including total number of symptoms reported and symptom severity scores on the
      Standardized Concussion Assessment Tool- 3rd edition (SCAT3). Methods: Eleven
      male collegiate soccer players were recruited to take part in three experimental
      conditions including heading, sham and control conditions. Participants were
      required to perform 40 headers in 20 min in the heading condition, and control 40
      soccer balls directed at them with their hands, chest or thigh in the sham
      condition. No ball contact was made during the control condition. Blood sampling
      and SCAT3 symptom assessments were completed prior to and 1 hour following
      conditions. A subset of participants returned 3 weeks following the heading
      condition for blood sampling. Results: NF-L was elevated at 1 hour (p=0.004) and
      1 month (p=0.04) following the heading condition, and at 1 hour (p=0.02)
      following the control condition. Tau levels remained unchanged following all
      conditions. The total number of symptoms (TS) and symptom severity (SS) scores
      from the SCAT3 were both elevated following the heading condition (p=0.01 and
      p=0.03, respectively). Both TS and SS decreased following sham (p=0.04 and
      p=0.04) and control conditions (p=0.04 and p=0.04). Conclusion: An acute bout of
      soccer heading is associated with increased NF-L concentrations at 1 hour and 1
      month following the session and can lead to symptoms commonly reported following
      sport-related concussion.

PMID- 30233811
TI  - The two-fold cost of sex: experimental evidence from a natural system.
AB  - Over four decades ago, John Maynard Smith showed that a mutation causing asexual
      reproduction should rapidly spread in a dioecious sexual population. His
      reasoning was that the per-capita birth rate of an asexual population would
      exceed that of a sexual population, because asexual females do not invest in
      sons. Hence, there is a cost of sexual reproduction that Maynard Smith called the
      "cost of males." Assuming all else is otherwise equal among sexual and asexual
      females, the cost is expected to be two-fold in outcrossing populations with
      separate sexes and equal sex ratios. Maynard Smith's model led to one of the most
      interesting questions in evolutionary biology: why is there sex? There are,
      however, no direct estimates of the proposed cost of sex. Here, we measured the
      increase in frequency of asexual snails in natural, mixed population of sexual
      and asexual snails in large outdoor mesocosms. We then extended Maynard Smith's
      model to predict the change in frequency of asexuals for any cost of sex and for
      any initial frequency of asexuals. Consistent with the "all-else equal"
      assumption, we found that the increase in frequency of asexual snails closely
      matched that predicted under a two-fold cost.

PMID- 30233812
TI  - Ixekizumab is efficacious when used alone or when added to conventional synthetic
      disease-modifying antirheumatic drugs (cDMARDs) in patients with active psoriatic
      arthritis and previous inadequate response or intolerance to tumour necrosis
      factor inhibitors.
AB  - Objective: To conduct subset analyses of SPIRIT-P2 (Standard Protocol Items:
      Recommendations for Interventional Trials, NCT02349295) to investigate the
      efficacy and safety of ixekizumab versus placebo in three subgroups of patients
      with active psoriatic arthritis (PsA) according to the concomitant conventional
      synthetic disease-modifying antirheumatic drug (cDMARD) received: any background
      cDMARDs (including methotrexate), background methotrexate only. Methods: Patients
      were randomised to receive placebo, ixekizumab 80 mg every 4 weeks (IXEQ4W) or
      every 2 weeks (IXEQ2W). Efficacy and safety were assessed when patients were
      subdivided according to cDMARD use at baseline. Efficacy was evaluated versus
      placebo at week 24 by the American College of Rheumatology criteria (ACR20/50),
      achievement of minimal disease activity (MDA) state, DiseaseActivityIndex for PsA
      (DAPSA), 28-joint DiseaseActivityScore using C reactive protein (DAS28-CRP),
      HealthAssessmentQuestionnaire-Disability Index and the 36-item Short-Form health
      survey physical functioning domain. Results: Regardless of background cDMARD
      status, ACR20, ACR50 and MDA response rates were significantly higher than
      placebo with IXEQ4W or IXEQ2W treatment. Similarly, significant improvements were
      observed relative to placebo for DAS28-CRP and DAPSA across subgroups. Physical
      function also significantly improved relative to placebo with IXEQ4W treatment
      regardless of background cDMARD status and with IXEQ2W alone. Percentages of
      reported treatment emergent adverse events (AEs), serious AEs (including serious
      infections) and discontinuations due to AEs in each subgroup were comparable to
      the overall SPIRIT-P2 population. Conclusion: Ixekizumab was efficacious in
      patients with active PsA and previous tumour necrosis factor inhibitor
      (TNFi)inadequate response or TNFi intolerance treated with ixekizumab alone or
      when added to cDMARDswith subgroup safety profiles that were consistent with that
      observed in the overall SPIRIT-P2 population.

PMID- 30233814
TI  - Correction: Secukinumab in the treatment of psoriatic arthritis: efficacy and
      safety results through 3 years from the year 1 extension of the randomised phase
      III FUTURE 1 trial.
AB  - [This corrects the article DOI: 10.1136/rmdopen-2018-000723.].

PMID- 30233813
TI  - Development of clinically apparent synovitis: a longitudinal study at the joint
      level during progression to inflammatory arthritis.
AB  - Introduction: Subclinical inflammation, detected by MRI, in patients with
      arthralgia is predictive for development of inflammatory arthritis (IA). However,
      within patients that develop IA, the course of inflammation at the joint level
      during this transition is unknown. This longitudinal study assessed progression
      of inflammation at the joint level. Methods: 350 joints (unilateral
      metacarpophalangeals (MCPs), wrist, metatarsophalangeal (MTP) joints) of 35
      patients presenting with clinically suspect arthralgia (CSA) that progressed to
      IA were studied at presentation with CSA and subsequently when clinical synovitis
      was first identified at joint examination (median time interval 17 weeks). At
      both time points, subclinical inflammation (bone marrow oedema, synovitis,
      tenosynovitis) was evaluated with MRI and joint examination was performed.
      Results: At presentation with CSA, 71 joints showed subclinical inflammation.
      During progression to IA, 20% of these joints had resolution of inflammation, 60%
      had persistent inflammation and 20% progressed to clinical synovitis. Of all
      joints that had developed clinical synovitis (n = 45), no prior subclinical
      inflammation was detected in 69%. Similar results were observed for
      anticitrullinated protein antibodies (ACPA)-positive and ACPA-negative patients.
      Conclusions: This longitudinal study demonstrated moderate correlations between
      joints with subclinical inflammation and joints that developed clinical
      synovitis. These data imply that IA development is a more systemic rather than a
      locally outgrowing process.

PMID- 30233815
TI  - Isolated medial collateral ligament tears: An update on management.
AB  - Tears of the medial collateral ligament (MCL) are the most common knee ligament
      injury.Incomplete tears (grade I, II) and isolated tears (grade III) of the MCL
      without valgus instability can be treated without surgery, with early functional
      rehabilitation.Failure of non-surgical treatment can result in debilitating,
      persistent medial instability, secondary dysfunction of the anterior cruciate
      ligament, weakness, and osteoarthritis.Reconstruction or repair of the MCL is a
      relatively uncommon procedure, as non-surgical treatment is often successful at
      returning patients to their prior level of function.Acute repair is indicated in
      isolated grade III tears with severe valgus alignment, MCL entrapment over pes
      anserinus, or intra-articular or bony avulsion. The indication for primary repair
      is based on the resulting quality of the native ligament and the time since the
      injury. Primary repair of the MCL is usually performed within 7 to 10 days after
      the injury.Augmentation repair for the superficial MCL (sMCL) is a surgical
      technique that can be used when the resulting quality of the native ligament
      makes primary repair impossible.Reconstruction is indicated when MCL injuries
      fail to heal in neutral or varus alignment. Reconstruction might be advisable to
      correct chronic instability. Chronic, medial-sided knee injuries with valgus
      misalignment should be treated with a two-stage approach. A distal femoral
      osteotomy should be performed first, followed by reconstruction of the medial
      knee structures. Cite this article: EFORT Open Rev 2018;3:398-407. DOI:
      10.1302/2058-5241.3.170035.

PMID- 30233818
TI  - Acromioclavicular joint injuries: diagnosis, classification and ligamentoplasty
      procedures.
AB  - Acromioclavicular (AC) joint injury is a frequent diagnosis after an acute
      shoulder trauma - often found among athletes and people involved in contact
      sports.This injury occurs five times more frequently in men than in women, with
      the highest incidence in the 20- to 30-year-old age group. Patients usually
      complain of pain and tenderness over the shoulder, particularly over the AC
      joint.Depending on the degree of injury, the clavicle may become prominent on the
      injured site.The original classification was described by Rockwood and Green
      according to the injured ligament complex and degree and direction of clavicular
      displacement.Many surgical procedures have been described; among these are
      screws, plates, muscle transfer, ligamentoplasty procedures and ligament
      reconstruction using either autograft or allografts.With the advancement of
      shoulder arthroscopy, surgeons are much more capable of performing mini-open or
      arthroscopically-assisted procedures, allowing patients an earlier return to
      their daily living activities. However, the results of conventional open
      techniques are still comparable.The introduction of new arthroscopic equipment
      provides a great variety of surgical procedures, though every new technique has
      its own advantages and pitfalls. Currently there is no gold standard for the
      surgical treatment of any type of AC injury, though it should be remembered that
      whenever an arthroscopic technique is chosen, the surgeon's expertise is likely
      to be the most significant factor affecting outcome. Cite this article: EFORT
      Open Rev 2018;3:426-433. DOI: 10.1302/2058-5241.3.170027.

PMID- 30233816
TI  - The interface between periacetabular osteotomy, hip arthroscopy and total hip
      arthroplasty in the young adult hip.
AB  - Hip pain is highly prevalent in both the younger and the elderly population. In
      older patients, pain arising from osteoarthritis (OA) is most frequent, whereas
      in younger patients, non-degenerative diseases are more often the cause of pain.
      The pain may be caused by hip dysplasia and femoroacetabular impingement
      (FAI).Abnormal mechanics of the hip are hypothesized by some authors to cause up
      to 80% of OA in the hip. Therefore, correction of these abnormalities is of
      obvious importance when treating young patients with hip pain.Hip dysplasia can
      be diagnosed by measuring a CE angle < 25 degrees  on a plain standing radiograph
      of the pelvis.Dysplastic or retroverted acetabulum with significant symptoms
      should receive a periacetabular osteotomy (PAO).FAI with significant symptoms
      should be treated by adequate resection and, if necessary, labrum surgery.If risk
      factors for poor outcome of joint-preserving surgery are present (age > 45 to 50
      years, presence of OA, joint space < 3 mm or reduced range of motion), the
      patient should be offered a total hip arthroplasty (THA) instead of PAO.THA can
      be performed following PAO with outcomes similar to a primary THA.Hip arthroscopy
      is indicated in FAI (cam and pincer) and/or for labral tears. Cite this article:
      EFORT Open Rev 2018;3:408-417. DOI: 10.1302/2058-5241.3.170042.

PMID- 30233817
TI  - Minimally invasive reduction and percutaneous fixation versus open reduction and
      internal fixation for displaced intra-articular calcaneal fractures: A systematic
      review of the literature.
AB  - The aim of this article is to systematically identify and analyse research
      evidence available to compare the outcomes of minimally invasive reduction and
      percutaneous fixation (MIRPF) versus open reduction and internal fixation (ORIF)
      for displaced intra-articular calcaneal fractures.Articles from 2000 to 2016 were
      searched through MEDLINE (PubMed), Cochrane Library, Embase, ScienceDirect,
      Scopus and ISI Web of Knowledge using Boolean logic and text words. Of the 570
      articles identified initially, nine were selected including three randomized
      controlled trials and six retrospective comparative studies.All nine studies had
      a total of 1031 patients with 1102 displaced intra-articular calcaneal fractures.
      Mean follow-up was 33 months. Of these, 602 (54.6%) were treated with MIRPF and
      500 (45.4%) were treated with ORIF.Overall incidence of wound-related
      complications in patients treated with MIRPF was 4.3% (0% to 13%) compared with
      21.2% (11.7% to 35%) in the ORIF groupFunctional outcomes were reported to be
      better in the minimally invasive group in all studies; however, the results did
      not reach statistical significance in some studies. All the studies had
      methodological flaws that put them at either 'unclear' or 'high' risk of bias for
      multiple domains.Overall quality of the available evidence is poor in support of
      either surgical technique due to small sample size, flaws in study designs and
      high risk of bias for various elements. Individual studies have reported
      minimally invasive techniques to be an effective alternative with lower risk of
      wound complications and better functional outcomes. Cite this article: EFORT Open
      Rev 2018;3:418-425. DOI: 10.1302/2058-5241.3.170043.

PMID- 30233819
TI  - State-of-the-art diagnosis and surgical treatment of acute peri-prosthetic joint
      infection following primary total hip arthroplasty.
AB  - Acute peri-prosthetic joint infection (PJI) following total hip arthroplasty
      (THA) is a potentially devastating and undesired complication, with a prevalence
      of 0.3% to 2.9%. Its suspicion begins with a meticulous physical examination and
      anamnesis. Diagnosis should be made on the basis of the Musculoskeletal Infection
      Society criteria. Serum and synovial biomarkers are very useful tools when major
      criteria are absent.Although sometimes not possible due to medical conditions,
      surgery is usually the first line of treatment. Although its outcome is highly
      correlated with the isolated microorganism, irrigation and debridement with
      implant retention (DAIR) is the gold standard for treatment. Ideally, the prior
      approach should be proximally and distally extended to augment the field of view
      and remove all of the prosthetic modular components, that is, femoral head and
      acetabular insert.Given DAIR's unclear control of infection, with successful
      outcomes in the range of 30% to 95%, one- or two-stage revision protocols may
      play a role in certain cases of acute infections; nonetheless, further
      prospective, randomized studies are necessary to compare long-term outcomes
      between DAIR and revision surgeries.Following surgical treatment, length of
      antibiotherapy is in the range of six weeks to six months, without any difference
      in outcomes between short and long protocols. Treatment should be adjusted to the
      isolated bacteria and controlled further with post-operative serum biomarker
      levels. Cite this article: EFORT Open Rev 2018;3:434-441. DOI: 10.1302/2058
      5241.3.170032.

PMID- 30233820
TI  - Predictive value of improvement in the immune tumour microenvironment in patients
      with breast cancer treated with neoadjuvant chemotherapy.
AB  - Background: Tumour-infiltrating lymphocytes (TILs) can be used to monitor the
      immune tumour microenvironment (iTME) and predict treatment response and outcome
      in breast cancer. We evaluated the prognostic significance of the levels of CD8+
      TILs and forkhead box protein (FOXP3)-positive TILs before and after neoadjuvant
      chemotherapy (NAC). Patients and methods: We examined 136 patients with breast
      cancer treated with NAC. The number of CD8+ TILs and FOXP3+ TILs in biopsy
      specimens and residual tumours was evaluated by immunohistochemistry. Results:
      Patients with a high rate of change in the CD8/FOXP3 ratio (CFR) had
      significantly better recurrence-free survival (RFS) (p<0.001, log-rank). In
      multivariate analysis, the rates of change in the CD8+ TIL levels and the CFR
      were independent predictors for RFS (HR=2.304, p=0.036 and HR=4.663, p<0.001). In
      patients with triple-negative and hormone receptor-positive breast cancer, the
      rate of change in the CFR was an independent predictor for RFS (HR=13.021,
      p=0.002 and HR=4.377, p=0.003). Conclusion: Improvement in the iTME following NAC
      is correlated with good outcome. The rate of change in the CFR may be a useful
      biomarker to predict prognosis of patients treated with NAC.

PMID- 30233822
TI  - Extra cost of brain metastases (BM) in patients with non-squamous non-small cell
      lung cancer (NSCLC): a French national hospital database analysis.
AB  - Purpose: To assess the incremental cost associated with the management of
      patients with primary non-squamous non-small cell lung cancer (NSCLC) with brain
      metastases at the time of diagnosis. Methods: Data were extracted from the French
      Hospital medical information database (Programme de Medicalisation des Systemes
      d'Information (PMSI)). Patients with non-squamous NSCLC were identified through a
      diagnosis of lung cancer and a prescription of bevacizumab or pemetrexed. All
      such patients hospitalised with lung cancer for the first time in 2013 and with
      metastases identified at the first hospitalisation were eligible. Two cohorts
      were identified, one with brain metastases (group B: n=971) and one with
      metastases at other sites (group A: n=1529). For each patient, total in-hospital
      medical resource consumption associated with the initial hospitalisation in 2013
      and with any follow-up stays in the following 24 months was documented. Costs
      were attributed from official French national tariffs and expressed in 2017
      euros. Results: The mean number of hospitalisations per patient in the 24-moth
      follow-up period was 17 in group A and 21 in group B. >99% of patients in both
      groups received chemotherapy. 58% of patients in group B and 13% in group A were
      managed by radiotherapy. 37% in group B and 24% in group A received palliative
      care. The associated cost was ?2979 per patient-month for patients in group B and
      ?2426 for patients in group A, representing a differential cost of ?553 per
      month. Radiotherapy (+?164/month) and palliative care (+?130/month) were the
      principal drivers of the incremental cost. Conclusions: The presence of brain
      metastases at the time of diagnosis of non-squamous NSCLC carries a significant
      burden, and ways of lowering this burden are needed.

PMID- 30233823
TI  - In the literature: August 2018.

PMID- 30233824
TI  - Cancer and the arts: a Pacifist's Guide to the War on Cancer.

PMID- 30233821
TI  - Somatic cancer genetics in the UK: real-world data from phase I of the Cancer
      Research UK Stratified Medicine Programme.
AB  - Introduction: Phase I of the Cancer Research UK Stratified Medicine Programme
      (SMP1) was designed to roll out molecular pathology testing nationwide at the
      point of cancer diagnosis, as well as facilitate an infrastructure where surplus
      cancer tissue could be used for research. It offered a non-trial setting to
      examine common UK cancer genetics in a real-world context. Methods: A total of 26
      sites in England, Wales and Scotland, recruited samples from 7814 patients for
      genetic examination between 2011 and 2013. Tumour types involved were breast,
      colorectal, lung, prostate, ovarian cancer and malignant melanoma. Centralised
      molecular testing of surplus material from resections or biopsies of
      primary/metastatic tissue was performed, with samples examined for 3-5 genetic
      alterations deemed to be of key interest in site-specific cancers by the National
      Cancer Research Institute Clinical Study groups. Results: 10 754 patients (98% of
      those approached) consented to participate, from which 7814 tumour samples were
      genetically analysed. In total, 53% had at least one genetic aberration detected.
      From 1885 patients with lung cancer, KRAS mutation was noted to be highly
      prevalent in adenocarcinoma (37%). In breast cancer (1873 patients), there was a
      striking contrast in TP53 mutation incidence between patients with ductal cancer
      (27.3%) and lobular cancer (3.4%). Vast inter-tumour heterogeneity of colorectal
      cancer (1550 patients) was observed, including myriad double and triple
      combinations of genetic aberrations. Significant losses of important clinical
      information included smoking status in lung cancer and loss of distinction
      between low-grade and high-grade serous ovarian cancers. Conclusion: Nationwide
      molecular pathology testing in a non-trial setting is feasible. The experience
      with SMP1 has been used to inform ongoing CRUK flagship programmes such as the
      CRUK National Lung MATRIX trial and TRACERx.

PMID- 30233825
TI  - Health systems research on access to medicines: unpacking challenges in
      implementing policies in the face of the epidemiological transition.

PMID- 30233826
TI  - Field detection devices for screening the quality of medicines: a systematic
      review.
AB  - Background: Poor quality medicines have devastating consequences. A plethora of
      innovative portable devices to screen for poor quality medicines has become
      available, leading to hope that they could empower medicine inspectors and
      enhance surveillance. However, information comparing these new technologies is
      woefully scarce. Methods: We undertook a systematic review of Embase, PubMed, Web
      of Science and SciFinder databases up to 30 April 2018. Scientific studies
      evaluating the performances/abilities of portable devices to assess any aspect of
      the quality of pharmaceutical products were included. Results: Forty-one devices,
      from small benchtop spectrometers to 'lab-on-a-chip' single-use devices, with
      prices ranging from <US$10 to >US$20 000, were included. Only six devices had
      been field-tested (GPHF-Minilab, CD3/CD3+, TruScan RM, lateral flow dipstick
      immunoassay, CBEx and Speedy Breedy). The median (range) number of active
      pharmaceutical ingredients (APIs) assessed per device was only 2 (1-20). The
      majority of devices showed promise to distinguish genuine from falsified
      medicines. Devices with the potential to assay API (semi)-quantitatively required
      consumables and were destructive (GPHF-Minilab, PharmaChk, aPADs, lateral flow
      immunoassay dipsticks, paper-based microfluidic strip and capillary
      electrophoresis), except for spectroscopic devices. However, the 10 spectroscopic
      devices tested for their abilities to quantitate APIs required processing complex
      API-specific calibration models. Scientific evidence of the ability of the
      devices to accurately test liquid, capsule or topical formulations, or to
      distinguish between chiral molecules, was limited. There was no comment on cost
      effectiveness and little information on where in the pharmaceutical supply chain
      these devices could be best deployed. Conclusion: Although a diverse range of
      portable field detection devices for medicines quality screening is available,
      there is a vitally important lack of independent evaluation of the majority of
      devices, particularly in field settings. Intensive research is needed in order to
      inform national medicines regulatory authorities of the optimal choice of
      device(s) to combat poor quality medicines.

PMID- 30233828
TI  - Artificial intelligence (AI) and global health: how can AI contribute to health
      in resource-poor settings?
AB  - The field of artificial intelligence (AI) has evolved considerably in the last 60
      years. While there are now many AI applications that have been deployed in high
      income country contexts, use in resource-poor settings remains relatively
      nascent. With a few notable exceptions, there are limited examples of AI being
      used in such settings. However, there are signs that this is changing. Several
      high-profile meetings have been convened in recent years to discuss the
      development and deployment of AI applications to reduce poverty and deliver a
      broad range of critical public services. We provide a general overview of AI and
      how it can be used to improve health outcomes in resource-poor settings. We also
      describe some of the current ethical debates around patient safety and privacy.
      Despite current challenges, AI holds tremendous promise for transforming the
      provision of healthcare services in resource-poor settings. Many health system
      hurdles in such settings could be overcome with the use of AI and other
      complementary emerging technologies. Further research and investments in the
      development of AI tools tailored to resource-poor settings will accelerate
      realising of the full potential of AI for improving global health.

PMID- 30233827
TI  - The coverage of continuum of care in maternal, newborn and child health: a cross
      sectional study of woman-child pairs in Ghana.
AB  - Introduction: The continuum of care has recently received attention in maternal,
      newborn and child health. It can be an effective policy framework to ensure that
      every woman and child receives timely and appropriate services throughout the
      continuum. However, a commonly used measurement does not evaluate if a pair of
      woman and child complies with the continuum of care. This study assessed the
      continuum of care based on two measurements: continuous visits to health
      facilities (measurement 1) and receiving key components of services (measurement
      2). It also explored individual-level and area-level factors associated with the
      continuum of care achievement and then investigated how the continuum of care
      differed across areas. Methods: In this cross-sectional study in Ghana in 2013,
      the continuum of care achievement and other characteristics of 1401 pairs of
      randomly selected women and children were collected. Multilevel logistic
      regression was used to estimate the factors associated with the continuum of care
      and its divergence across 22 areas. Results: Throughout the pregnancy, delivery
      and post-delivery stages, 7.9% of women and children achieved the continuum of
      care through continuous visits to health facilities (measurement 1). Meanwhile,
      10.3% achieved the continuum of care by receiving all key components of maternal,
      newborn and child health services (measurement 2). Only 1.8% of them achieved it
      under both measurements. Women and children from wealthier households were more
      likely to achieve the continuum of care under both measurements. Women's
      education and complications were associated with higher continuum of care
      services-based achievement. Variance of a random intercept was larger in the
      continuum of care services-based model than the visit-based model. Conclusions:
      Most women and children failed to achieve the continuum of care in maternal,
      newborn and child health. Those who consistently visited health facilities did
      not necessarily receive key components of services.

PMID- 30233830
TI  - Clubfoot treatment in 2015: a global perspective.
AB  - Introduction: Clubfoot affects around 174 000 children born annually, with
      approximately 90% of these in low-income and middle-income countries (LMIC).
      Untreated clubfoot causes life-long impairment, affecting individuals' ability to
      walk and participate in society. The minimally invasive Ponseti treatment is
      highly effective and has grown in acceptance globally. The objective of this
      cross-sectional study is to quantify the numbers of countries providing services
      for clubfoot and children accessing these. Method: In 2015-2016, expected cases
      of clubfoot were calculated for all countries, using an incidence rate of
      1.24/1000 births. Informants were sought from all LMIC, and participants
      completed a standardised survey about services for clubfoot in their countries in
      2015. Data collected were analysed using simple numerical analysis, country
      coverage levels, trends over time and by income group. Qualitative data were
      analysed thematically. Results: Responses were received from 55 countries, in
      which 79% of all expected cases of clubfoot were born. More than 24 000 children
      with clubfoot were enrolled for Ponseti treatment in 2015. Coverage was less than
      25% in the majority of countries. There were higher levels of response and
      coverage within the lowest income country group. 31 countries reported a national
      programme for clubfoot, with the majority provided through public-private
      partnerships. Conclusion: This is the first study to describe global provision
      of, and access to, treatment services for children with clubfoot. The numbers of
      children accessing Ponseti treatment for clubfoot in LMIC has risen steadily
      since 2005. However, coverage remains low, and we estimate that less than 15% of
      children born with clubfoot in LMIC start treatment. More action to promote the
      rollout of national clubfoot programmes, build capacity for treatment and enable
      access and adherence to treatment in order to radically increase coverage and
      effectiveness is essential and urgent in order to prevent permanent disability
      caused by clubfoot.

PMID- 30233829
TI  - Determining environmental and anthropogenic factors which explain the global
      distribution of Aedes aegypti and Ae. albopictus.
AB  - Background: Responsible for considerable global human morbidity and mortality,
      Aedes aegypti and Ae. albopictus are the primary vectors of several important
      human diseases, including dengue and yellow fever. Although numerous variables
      that affect mosquito survival and reproduction have been recorded at the local
      and regional scales, many remain untested at the global level, potentially
      confounding mapping efforts to date. Methods: We develop a modelling ensemble of
      boosted regression trees and maximum entropy models using sets of variables
      previously untested at the global level to examine their performance in
      predicting the global distribution of these two vectors. The results show that
      accessibility, absolute humidity and annual minimum temperature are consistently
      the strongest predictors of mosquito presence. Both vectors are similar in their
      response to accessibility and humidity, but exhibit individual profiles for
      temperature. Their mapped ranges are therefore similar except at peripheral
      latitudes, where the range of Ae. albopictus extends further, a finding
      consistent with ongoing trapping studies. We show that variables previously
      identified as being relevant, including maximum and mean temperatures, enhanced
      vegetation index, relative humidity and population density, are comparatively
      weak performers. Results: The variables identified represent three key biological
      mechanisms. Cold tolerance is a critical biological parameter, controlling both
      species' distribution northwards, and to a lesser degree for Ae. albopictus which
      has consequent greater inland suitability in North America, Europe and East Asia.
      Absolute humidity restricts the distribution of both vectors from drier areas,
      where moisture availability is very low, and increases their suitability in
      coastal areas. The latter is exacerbated by accessibility with increased
      likelihood of vector importation due to greater potential for human and trade
      movement. Conclusion: Accessibility, absolute humidity and annual minimum
      temperatures were the strongest and most robust global predictors of Ae. aegypti
      and Ae. albopictus presence, which should be considered in control efforts and
      future distribution projections.

PMID- 30233831
TI  - Does supportive legislation guarantee access to pregnancy termination and
      postabortion care services? Findings from a facility census in Central Province,
      Zambia.
AB  - Introduction: Zambia is one of the few countries in Africa to permit termination
      of pregnancy (TOP) on a wide range of grounds. However, substantial barriers
      remain to TOP and postabortion care (PAC). Methods: We conducted a census of 153
      facilities between March and May 2016. We defined facilities according to whether
      they met basic and/or comprehensive signal functions criteria for TOP and PAC. We
      linked our facility data to census data to estimate geographic accessibility
      under different policy scenarios. Results: Overall, 16% of facilities reported
      they had performed a TOP and 39% performed a PAC in the last year. Facilities
      were twice as likely to use medical methods for TOP compared with surgical
      methods, and four times more likely for PAC. Considerably more facilities had
      performed TOP or PAC than met the basic or comprehensive signal functions
      criteria, indicating services were being performed in facilities below essential
      quality standards. Under current Zambian law for non-emergency scenarios, 21% of
      women in Central Province lived within 15 km of a facility with basic capability
      to provide TOP; if midlevel providers were trained to provide TOP, this would
      increase to 36%. Conclusion: A supportive legislative framework is essential, but
      not in itself sufficient, for adequate access to services. Training midlevel
      providers, in line with WHO guidance, and ensuring equipment is available in
      primary care can increase accessibility of TOP and PAC. While both medical and
      surgical methods need to be available, medical abortion is a safe and effective
      method that can be provided in low-resource settings.

PMID- 30233832
TI  - Institutionalising an evidence-informed approach to guideline development:
      progress and challenges at the World Health Organization.
AB  - This study explored experiences, perceptions and views among World Health
      Organization (WHO) staff about the changes, progress and challenges brought by
      the guideline development reforms initiated in 2007. Thirty-five semistructured
      interviews were conducted with senior WHO staff. Sixteen of the interviewees had
      in-depth experience with WHO's formal guideline development process. Thematic
      analysis was conducted to identify key themes in the qualitative data, and these
      were interpreted in the context of the existing literature on WHO's guideline
      development processes. First, the reforms were seen to have transformed and
      improved the quality of WHO's guidelines. Second, independent evaluation and
      feedback by the Guidelines Review Committee (GRC) was described to have
      strengthened the legitimacy of WHO's recommendations. Third, WHO guideline
      development processes are not yet designed to systematically make use of all
      types of research evidence needed to inform decisions about health systems and
      public health interventions. For example, several interviewees expressed
      dissatisfaction with the insufficient attention paid to qualitative evidence and
      evidence from programme experience, and how the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) process evaluates the quality of
      evidence from non-randomised study designs, while others believed that GRADE was
      just not properly understood or applied. Fourth, some staff advocated for a more
      centralised quality assurance process covering all outputs from WHO's departments
      and scientific advisory committees, especially to eliminate strategic efforts
      aimed at bypassing the GRC's requirements. Overall, the 'culture change' senior
      WHO staff called for over 10 years ago appears to have gradually spread
      throughout the organisation. However, at least two major challenges remain: (1)
      ensuring that all issued advice benefits from independent evaluation, monitoring
      and feedback for quality and (2) designing guideline development processes to
      better acquire, assess, adapt and apply the full range of evidence that can
      inform recommendations on health systems and public health interventions.

PMID- 30233833
TI  - Systematic debriefing after qualitative encounters: an essential analysis step in
      applied qualitative research.
AB  - Conversations regarding qualitative research and qualitative data analysis in
      global public health programming often emphasize the product of data collection
      (audio recordings, transcripts, codebooks and codes), while paying relatively
      less attention to the process of data collection. In qualitative research,
      however, the data collector's skills determine the quality of the data, so
      understanding data collectors' strengths and weaknesses as data are being
      collected allows researchers to enhance both the ability of data collectors and
      the utility of the data. This paper defines and discusses a process for
      systematic debriefings. Debriefings entail thorough, goal-oriented discussion of
      data immediately after it is collected. Debriefings take different forms and
      fulfill slightly different purposes as data collection progresses. Drawing from
      examples in our health systems research in Tanzania and Sierra Leone, we
      elucidate how debriefings have allowed us to: enhance the skills of data
      collectors; gain immediate insights into the content of data; correct course amid
      unforeseen changes and challenges in the local context; strengthen the quality
      and trustworthiness of data in real time; and quickly share emerging data with
      stakeholders in programmatic, policy and academic spheres. We hope this article
      provides guidance and stimulates discussion on approaches to qualitative data
      collection and mechanisms to further outline and refine debriefings in
      qualitative research.

PMID- 30233834
TI  - The sex gap in neonatal mortality and the AIDS epidemic in sub-Saharan Africa.

PMID- 30233835
TI  - Towards equity in global health partnerships: adoption of the Research Fairness
      Initiative (RFI) by Portuguese-speaking countries.

PMID- 30233836
TI  - Essential surgery as a key component of primary health care: reflections on the
      40th anniversary of Alma-Ata.

PMID- 30233837
TI  - Emerging role of family medicine in South Africa.

PMID- 30233838
TI  - Immunotherapy and molecular role of T-cell in PD-1 antibody treated resectable
      lung cancer patients.

PMID- 30233839
TI  - Neoadjuvant PD-1 blockade in lung cancer: we're not in Kansas anymore.

PMID- 30233840
TI  - Tumor mutational burden (TMB) as a biomarker of response to immunotherapy in
      small cell lung cancer.

PMID- 30233841
TI  - Impact of abnormal longitudinal rotation on the assessment of right ventricular
      systolic function in patients with severe pulmonary hypertension.
AB  - Background: Assessment of right ventricular (RV) function plays an important role
      in patients with cardiopulmonary disease, and current guidelines recommend
      parameters including tricuspid annular plane systolic excursion (TAPSE) and right
      ventricular systolic excursion velocity (RVS') to assess RV longitudinal
      function. We assessed the hypothesis that the previously undescribed motion of RV
      longitudinal rotation (RVLR) is an independent predictor of both TAPSE and RVS'.
      Methods: We assessed a series of 100 consecutive patients with pulmonary
      hypertension (PH) undergoing echocardiography. Patients with left ventricular
      (LV) dilation and dysfunction were excluded. Standard RV parameters were
      determined using established guidelines, while RVLR and right ventricular global
      longitudinal strain (RVGLS) measurements were performed using 2-dimensional (2D)
      speckle tracking technique. Results: Mean peak RVLR measured -4.2+/-3.7 degrees.
      By convention, negative values implied clockwise motion. In a multiple linear
      regression model, TAPSE could be predicted from a combination of RVLR and RVGLS
      (R=0.56, P<0.001). A similar relationship was found for RVS' which could also be
      predicted from a combination of RVLR and RVGLS (R=0.52, P<0.001). While no
      association was found between RVLR and RV size, estimated RV systolic pressure
      (RVSP) or the presence of a pericardial effusion, a mild correlation was noted
      between RVLR and QRS duration (R=0.25, P=0.01). Conclusions: RVLR is an
      independent predictor of TAPSE and RVS'. Awareness of this motion should be
      considered in the interpretation of TAPSE and RVS' values as markers of RV
      systolic function, as abnormal RVLR may account for exaggerated values,
      particularly in patients with PH and RV dysfunction.

PMID- 30233842
TI  - Sequential changes of serum KL-6 predict the progression of interstitial lung
      disease.
AB  - Background: Interstitial lung disease (ILD) is a slowly progressing fatal
      fibrotic lung disease with a widely variable clinical course and a poor
      prognosis. Clinicians and patients would benefit from a highly efficient and
      accurate predictor for ILD. The purpose of this study was to evaluate whether
      blood biomarkers can predict ILD progression. Methods: In this study, 85 patients
      diagnosed as having ILD at the Guangzhou Institute of Respiratory Health
      participated, including 20 patients with idiopathic pulmonary fibrosis (IPF).
      During the mean follow-up time of 12 months, every patient was examined during
      four or five visits in our center. Serum samples were collected at baseline, and
      after 1, 2, 6, and 12 months and tested for the Klebs von den Lungen-6 (KL-6)
      concentration. Dynamic fluctuations in this biomarker concentration were examined
      using a logistic regression model to see if they reflected the progression of
      ILD. Results: The baseline levels of serum KL-6 in the ILD patients were
      significantly increased compared to healthy controls. Serum KL-6 levels were
      significantly elevated in patients with progression of disease (1,985.2+/-1,497.8
      vs. 1,387.6+/-1,313.1 ug/mL; P<0.001). Logistic regression revealed sequential
      changes of KL-6 was a significant predictor of ILD progression in the next follow
      up (OR, 2.569; 95% CI, 2.260-2.880; P=0.001), and that sequential changes of KL-6
      were significant predictors for the progression of IPF (OR, 3.611; 95% CI, 1.048
      12.442; P<0.01). Baseline concentrations were not predictive for ILD or IPF.
      Univariate Cox analysis showed that KL-6 was significantly associated with
      survival [relative risk (RR), 1.901; 95% CI, 1.294-2.793; P<0.001], along with
      other variables. Conclusions: Serum levels of KL-6 were elevated in ILD patients
      with severe respiratory function compared to those without. The rate of poor
      prognosis and mortality was associated with increased biomarker concentrations.
      Sequential measurements of biomarkers could be valuable in disease monitoring and
      evaluations in clinical management.

PMID- 30233843
TI  - Neoadjuvant chemotherapy with or without neoadjuvant radiotherapy compared with
      neoadjuvant chemoradiotherapy for esophageal cancer.
AB  - Background: Although it was controversial for treating locally advanced
      resectable esophageal squamous cell carcinoma (ESCC), neoadjuvant
      chemoradiotherapy (NACR) was more widely accepted rather than neoadjuvant
      chemotherapy (NAC) worldwide. With the development of paclitaxel, a high response
      rate to NAC was reported in many studies. Our hypothesis is that lots of patients
      could get a response from NAC alone and avoid unnecessary NACR. Those who had no
      response from NAC could still response from the followed radiotherapy. We
      attempted to circumvent the controversy over the use of NAC, NACR and made a
      combined version, NAC +/- neoadjuvant radiotherapy (NAR). Methods: The
      retrospective study compared NAC +/- NAR with NACR between June 30, 2015 and
      October 31, 2016. Sixty consecutive borderline resectable ESCC were included:
      thirty-one in NAC +/- NAR group and 29 in NACR group. The toxicities, response
      rates, operative data, complications, length of stay, and overall survival (OS)
      rates were evaluated. Results: The response rate to NAC +/- NAR was 93.5%; to
      NACR was 86.2%. There was no grade 3-4 non-hematologic adverse events after NAC
      +/- NAR, but three in the NACR group. Arrhythmias (6.5% vs. 37.9%, P=0.003),
      pneumonitis (25.8% vs. 51.7%, P=0.039) and anastomotic leakage (0% vs. 13.8%,
      P=0.049) were more likely in NACR group. Postoperative hospitalization stays were
      significantly prolonged in the NACR (9 vs. 16 d, P<0.001). A point estimate of
      the 2-year OS rate of the NAC +/- NAR group was 84.0%, the NACR group 80.7%
      (P=0.410). Conclusions: Compared with NACR, the NAC +/- NACR provided the same
      survival benefits but low post operation complication rate. In the future, it
      might be a choice for locally advanced ESCC.

PMID- 30233844
TI  - Diagnostic value of KL-6 in idiopathic interstitial pneumonia.
AB  - Background: Idiopathic interstitial pneumonia (IIP) can induce type II alveolar
      epithelial cell proliferation and pulmonary basement membrane damage and
      subsequent release of Krebs von den Lungen-6 antigen (KL-6) to the bloodstream.
      This study investigated the diagnostic and prognostic value of serum KL-6 levels
      for IIP. Methods: One hundred five patients with lung disease were divided into
      IIP (n=75) and non-IIP groups (n=30) according to pathological and computed
      tomography findings. Serum KL-6 levels were evaluated in blood samples from all
      subjects. Nineteen IIP group patients were also subjected to a longitudinal study
      of disease progression and serum KL-6 levels over time. Results: Serum KL-6
      levels were significantly higher in the IIP group vs. the non-IIP group [1,096.0
      (565.0-1,544.0) vs. 226.0 (173.5-346.5) U/mL; P<0.01]. Within the IIP group,
      serum KL-6 levels differed significantly between patients with and without
      concomitant disease or pulmonary infection (Z=-2.475, P=0.013). In a receiver
      operating characteristic (ROC) curve analysis, the area below the curve for serum
      KL-6 was 0.911 [95% confidence interval (CI): 0.847-0.975, P<0.001], indicating a
      good diagnostic performance for IIP, with a cut-off level of 485 U/mL,
      sensitivity of 85.33%, specificity of 90.00%, positive predictive value (PPV) of
      95.52%, negative predictive value (NPV) of 71.05%, and Kappa value of 0.70.
      Accordingly, the serum KL-6 and clinical diagnostic results were consistent.
      Moreover, in the longitudinal study, the serum KL-6 levels differed significantly
      from before to after treatment in patients with exacerbated or improved disease
      (P=0.004 and P=0.043, respectively), whereas no obvious changes were observed in
      patients with stable disease (P=0.692). Conclusions: The serum KL-6 level is a
      valuable and significant diagnostic marker of IIP and a useful predictor of
      clinical prognosis.

PMID- 30233845
TI  - Deletion of ACTA2 in mice promotes angiotensin II induced pathogenesis of
      thoracic aortic aneurysms and dissections.
AB  - Background: Mutation of the ACTA2 (alpha-2 smooth muscle actin) gene accounts for
      ~15% of all cases of familial thoracic aortic aneurysms and dissections.
      Surprisingly, no severe vascular phenotypes were observed at baseline in mice
      carrying this gene mutation. Our aim was to explore whether mutation of ACTA2
      promotes the development of aneurysms or dissections in the presence of
      angiotensin II (AngII) and to determine whether this mutation has an impact on
      the phenotypic modulation and apoptosis mediated by AngII in vascular smooth
      muscle cells (VSMCs). Methods: Mice were divided into three groups: AngII
      stimulated-wild-type (WT) (AngII) and ACTA2-/- mice (ACTA2) group, in which AngII
      were administered subcutaneously into 8-week-old C57 mice and ACTA2-/- mice,
      respectively, for 4 weeks using osmotic minipumps, and the control group (WT), in
      which the WT mice were infused with normal saline (NS). Ultrasound was performed
      to quantify lumen diameters. RT-qPCR and Western blot were used to assess gene
      expression, and histobiochemistry was used to evaluate the pathological changes
      in the thoracoabdominal aortas. TUNEL was used to assess apoptosis in VSMCs.
      Results: Compared with the AngII- group, the ACTA2 mice exhibited more severity
      of dilated lumena of the aortas, a significantly increased expression of
      osteopontin (OPN), an elevated ratio of Bax/Bcl-2, increased apoptosis, and a
      decreased expression of alpha-smooth muscle actin (alpha-SMA). Conclusions:
      Knockout of ACTA2 promoted AngII induced progressive lumen dilation of the
      aortas, apoptosis, and the phenotypic modulation in VSMCs in mice.

PMID- 30233846
TI  - High CCR4 expression in the tumor microenvironment is a poor prognostic indicator
      in lung adenocarcinoma.
AB  - Background: Clinical trials of anti-CCR4 antibody for solid cancers with or
      without other immune-modulating agents including immune checkpoint blockade
      therapy are currently underway. However, little is known about the roles of CCR4+
      lymphocytes and their prognostic impact in lung cancer. We hypothesized that high
      CCR4 expression in the tumor microenvironment would be associated with a poor
      prognosis and would act as a biomarker in lung adenocarcinoma. Methods: First,
      the prognostic impact of CCR4 gene expression was explored using pooled data from
      public transcriptomic databases with online survival analysis software. Second,
      tissue microarrays (TMAs) were constructed from resected lung adenocarcinoma
      specimens from tumors up to 3 cm in size. The density of CCR4+ lymphocytes
      infiltrating the tumor was then assessed by immunohistochemistry and related to
      survival. Confounding factors were controlled for by multivariate analysis using
      the Cox proportional hazards model. Results: Higher than median expression of the
      CCR4 gene was identified as an independent poor prognostic factor for overall
      survival (OS) by multivariate analysis of 720 lung adenocarcinoma patients in the
      public databases [HR =1.55 (95% CI: 1.03-2.35), P=0.037]. Consistent with this,
      high CCR4+ tumor-infiltrating lymphocyte (TIL) density was found to be an
      independent poor prognostic factor for both OS [HR =2.24 (1.01-5.34), P=0.049]
      and recurrence-free survival (RFS) [HR =2.20 (1.16-4.39), P=0.017] in the
      patients from whom TMA were obtained (n=180). Age, male gender, predominantly non
      lepidic histological subtype, nodal involvement, and low CD8+ TIL density were
      also independent poor prognostic factors. However, FOXP3 gene expression and
      Foxp3+ lymphocyte infiltration did not possess any prognostic value in either
      study. Conclusions: High CCR4 expression in the tumor microenvironment may be a
      poor prognostic factor in lung adenocarcinoma. Patients with high CCR4+
      lymphocyte infiltration may have a poor prognosis and thus be suitable candidates
      for clinical trials of anti-CCR4 antibody treatment.

PMID- 30233847
TI  - Incidence and risk factors of chronic thromboembolic pulmonary hypertension after
      acute pulmonary embolism: a systematic review and meta-analysis of cohort
      studies.
AB  - Background: The incidence and risk factors of chronic thromboembolic pulmonary
      hypertension (CTEPH) after acute pulmonary embolism (PE) were still
      controversial. A systematic review and meta-analysis was conducted to assess the
      incidence and risk factors of CTEPH after acute PE. Methods: Embase, Medline,
      China National Knowledge Infrastructure, Wanfang databases, and various reference
      lists were searched to identify studies published up to May 2018. Only cohort
      studies that used right heart catheterization for CTEPH diagnosis were included.
      The study quality was assessed using the Newcastle-Ottawa Scale (NOS). All
      analyses were conducted with the meta package in R software (3.2.2). Results:
      Fifteen studies met the inclusion criteria. The overall incidence of CTEPH after
      acute PE, with a median follow-up from 6 to 94.3 months, was 3.13% (95% CI: 2.11
      4.63%). The incidence of studies from China [4.46% (95% CI: 1.68-11.32%)] was
      slightly higher than from Europe [2.82% (95% CI: 1.82-4.34%)]. However, there was
      no significant difference between these two groups (P=0.39). Subgroup analyses of
      confirmed diagnostic method showed that compared studies using right heart
      catheterization [3.25% (95% CI: 2.12-4.97%)], studies using right heart
      catheterization combined with bundled tests tended to yield a similar data [2.40%
      (95% CI: 0.97-5.81%), P=0.54]. Previous/recurrent PE or previous VTE, idiopathic
      PE and right heart dysfunction were considered as risk factors of CTEPH in
      patients with a previous PE. Conclusions: CTEPH is not a rare complication of
      acute PE. Close follow-up and implementation of a comprehensive screening program
      are important, especially in patients with independent risk factors.

PMID- 30233848
TI  - Does age over 80 years have to be a contraindication for lung cancer surgery-a
      nationwide database study.
AB  - Background: Nowadays surgery remains the best treatment for localized lung cancer
      (LC). However, patients over 80 years old are often denied surgery because of the
      postoperative risk of death. This study aimed to estimate in-hospital mortality
      (IHM) and determine whether age over 80 is the most important predictor of IHM
      after LC surgery. Methods: From January 2005 to December 2015, 97,440 patients,
      including 4,438 patients over 80 years old, were operated on for LC and recorded
      in the French Administrative Database. Characteristics of patients, hospitals and
      surgery were analysed. Results: Crude IHM was 3.73% (n=3,639) and 7.77% (n=345)
      for the over 80s vs. 3.54% (n=3,294) for younger patients (P<0.0001). In
      multivariate analysis, predictive factors for IHM with the odds ratios (OR) were:
      2.60 for age >=80 (95% CI: 2.30-2.94; P=0.0001), 5.85 for a previous liver
      disease (95% CI: 4.79-7.16; P=0.0001) and 5 for previous lung disease (95% CI:
      4.25-5.9; P=0.0001). IHM was also linked to hospital volume with an OR of 0.75
      (95% CI: 0.69-0.81; P=0.0001) and a linear decrease for predicted IHM according
      to hospital volume for the over 80s. Adjusted ORs were 1.15 (95% CI: 0.96-1.4;
      P=0.0116) for lobectomy, 2.18 for bilobectomy (95% CI: 1.7-2.8; P=0.0001) and
      3.83 (95% CI: 3.2-4.6; P=0.0001) for pneumonectomy. Conclusions: Concerning IHM,
      age >=80 had a lower weight than did a previous pulmonary or liver disease and
      the type of pulmonary resection. Patients over 80s with localized LC and no
      significant comorbidities should be referred for surgery if lobectomy or sublobar
      resection could be performed.

PMID- 30233849
TI  - Application value of the NoSAS score for screening sleep-disordered breathing.
AB  - Background: Diagnosis of sleep-disordered breathing (SDB) requires overnight
      polysomnography (PSG). Because of the cost and low availability of these
      procedures, the NoSAS score was developed to identify subjects at high risk of
      SDB. To evaluate the clinical utility of the NoSAS score for screening patients
      with SDB in China and to compare the predictive value of the NoSAS score with the
      Epworth Sleepiness Scale (ESS), we used the STOP-Bang questionnaire and the
      Berlin questionnaire. Methods: In our study, we retrospectively reviewed the
      existing clinical data of patients who underwent an overnight PSG for suspected
      SDB from June 2014 to September 2017 at the sleep medical center of Guangdong
      Medical University Affiliated Second Hospital. The information we collected
      included all parts of the NoSAS score, the ESS, the STOP-Bang questionnaire and
      the Berlin questionnaire. Based on the severity of SDB determined by the apnea
      hypopnea index (AHI), the patients were classified into four groups of primary
      snoring (<5 events/h), mild SBD (AHI >=5 and <15 events/h), moderate SBD (AHI
      >=15 and <=30 events/h) and severe SBD (>30 events/h). We calculated the
      sensitivity, specificity, positive predictive value, negative predictive value
      and area under the receiver operating characteristic curve of the five
      questionnaires to compare their relative efficacy for screening SDB. Results: A
      total of 479 consecutive patients (374 males and 105 females) ranging in age from
      18 to 80 years old (mean +/- SD, 48.9+/-14.4 years old) were recruited into this
      study. When using the standard of AHI >=5 for diagnosing SDB, the NoSAS score had
      the largest area under the curve (AUC) (AUC =0.734), and the Berlin questionnaire
      (AUC =0.732) came second. Both exhibited a better predictive value than the ESS
      score and the STOP-Bang questionnaire. Using NoSAS >=8 to predict AHI >=5
      events/h, AHI >=15 events/h and AHI >30 events/h, the sensitivity and specificity
      were 0.590 and 0.707, 0.649 and 0.626, and 0.644 and 0.562, respectively; for the
      STOP-Bang questionnaire, the values were 0.721 and 0.512, 0.752 and 0.440, and
      0.763 and 0.399, respectively; and for the Berlin questionnaire, the values were
      0.721 and 0.512, 0.752 and 0.440, and 0.763 and 0.399, respectively. Conclusions:
      The NoSAS score and the Berlin questionnaire both exhibited good predictive value
      for SDB patients. NoSAS is a more suitable questionnaire to use in clinic for the
      conveniences but the similar performance with another questionnaire.

PMID- 30233850
TI  - Health-related quality of life evaluation in patients with non-surgical benign
      tracheal stenosis.
AB  - Background: The primary objective of the study was to evaluate the health-related
      quality of life (HRQL) of patients with benign post-intubation tracheal stenosis
      considered as unfit for surgical treatment. Secondary objectives were: (I) to
      determine if clinical variables (gender, age, total treatment time, and type of
      tracheal device) could influence HRQL and (II) to compare the results with a
      normal standardized population. Methods: Prospective study between August-2014
      and December-2016 including patients with tracheal stenosis treated with silicone
      stents, T-Tubes or tracheostomy. Candidates to airway resection and
      reconstruction were excluded from the analysis. HRQL was assessed with the SF-36
      Health Questionnaire. Backward stepwise regression model analyzed the influence
      of clinical variables on the SF-36 domains and component summaries. Norm-based
      results were compared with normative data. Alpha error was 5%. Results: Ninety
      three patients (62M/31F; mean age 38+/-14 years) were included. Mean overall HRQL
      in all 8 SF-36 domains was poor. Lowest scores were in the role physical (mean
      31.7+/-38), bodily pain (mean 39.2+/-35), and role emotional domain (mean 48.7+/
      40). The physical component summary (PCS) was more affected than the mental
      (P<0.001). Norm-based results indicated that most domains and both physical and
      mental summaries were below the mean for the USA normative population. Total
      stenting time significantly influenced the physical (P=0.001) and mental
      component summaries (P=0.001). Conclusions: Quality of life of patients with
      benign tracheal stenosis is severely impaired, and norm-based results indicate
      that the HRQL is below normative data. Physical and mental discomfort seems to be
      attenuated by total treatment time.

PMID- 30233851
TI  - Right mini-thoracotomy approach reduces hospital stay and transfusion of mitral
      or tricuspid valve reoperation with non-inferior efficacy: evidence from
      propensity-matched study.
AB  - Background: There is limited evidence about the efficacy and cost difference
      between minimally invasive and conventional valve reoperation. This study
      intended to compare the short-term efficacy and cost between right mini
      thoracotomy approach and median sternotomy approach in valve reoperation.
      Methods: From Feb 2011 to Sep 2017, 156 patients underwent valve reoperation
      including 68 cases of minimally invasive approach and 88 cases of traditional
      median sternotomy approach in our hospital. A propensity scoring was used to
      match patients with similar demographic characteristics. A total of 42 pairs of
      patients were left and divided into the conventional sternotomy group (CS group)
      and the right mini-thoracotomy group (RT group). A retrospective study of
      efficacy and cost was conducted between two groups. Results: There was no
      statistical difference between two groups in demographical characteristics after
      propensity-scoring match (P>0.05). In-hospital mortality was 11.9% (5/42) for CS
      group and 7.1% (3/42) for the RT group (P=0.687). No significant disparity was
      found in the incidence of complications between two groups (P>0.05). CPB time
      (P=0.012), bypass time (P=0.006) and operation time (P=0.003) of CS group were
      significantly higher than RT group. Blood loss (P=0.014) and transfusion volume
      (P=0.003) of RT group was less than CS group. Shorter ICU and hospital stay was
      seen in RT group compared with CS group (P<0.001). Though the materials cost of
      RT group was higher than CS group (P<0.001), no significant disparity was found
      in total cost between CS group and RT group (P=0.790). Conclusions: The right
      mini-thoracotomy approach can achieve equivalent efficacy with conventional
      median approach, and doesn't necessarily increase the total cost. Moreover, the
      minimally invasive approach can decrease the operation time, hospital stay and
      blood product transfusion.

PMID- 30233852
TI  - Nine cases of catamenial pneumothorax: a report of a single-center experience.
AB  - Background: Catamenial pneumothorax (CP) is defined as repeated pneumothorax
      related to menses and thoracic endometriosis. We performed a retrospective
      analysis of nine patients with CP to determine the clinical features as well as
      the effects of treatment and recurrence rates. Methods: A retrospective review
      was conducted of the clinical and pathologic data in all CP patients undergoing
      treatment at our institution. Nine patients underwent treatment for CP. Of these,
      six underwent surgical treatment 8 times. Results: The median age was 36 years.
      Six patients had experienced delivery. The laterality of the pneumothorax was
      right in all patients. Pelvic endometriosis was diagnosed in five patients. Six
      patients underwent surgical treatment. Partial resection of the lung was
      performed in four patients and partial resection of the diaphragm in five. Of
      these, both resections were performed in four patients. A pathological diagnosis
      of endometriosis was achieved in only three patients. The observation period was
      16.7 months. In the six patients with surgical resection, five experienced
      recurrence at various intervals. Onset of pneumothorax occurred pre- or menstrual
      period in most cases. Conclusions: The diagnosis and treatment of CP is not easy.
      A multidisciplinary approach and skillful management are required. Recurrence of
      CP is common following a temporary cure of pneumothorax by surgical treatment.

PMID- 30233853
TI  - Long term and disease-free survival following surgical resection of occult N2
      lung cancer.
AB  - Background: Despite systematic investigation with computed tomography (CT),
      positron emission tomography (PET)/CT, CT or magnetic resonance imaging (MRI)
      brain imaging and supplementary investigation using endobronchial ultrasound
      guided biopsy (EBUS), endo-oesophageal ultrasound guided biopsy (EUS), fine
      needle aspiration (FNA), mediastinoscopy or mediastinotomy, there is an
      approximately 10% rate of occult N2 disease identified at pathological staging.
      It has been hypothesised that such occult disease, too small or inactive to be
      identified during pre-operative multi-modality staging, may represent low volume
      disease that may have equivalent survival to patients with similar stage at
      clinical, pre-operative assessment. We compared the long-term survival and
      disease-free survival of patients with the same clinical TNM stage with and
      without occult N2 disease. Methods: We retrospectively analysed a database that
      prospectively captured information on all patients assessed and treated for lung
      cancer in our surgical unit. We reviewed data on patients who underwent lung
      cancer surgery with curative intent between January 2006 and August 2010.
      Results: A total of 312 lung cancer resections were performed [mean age 68
      (range, 42-86) years old and male:female ratio 1.14:1]. Occult N2 disease was
      identified in 28 (8.7%) of 312 patients. There was no difference in the rate of
      N2 disease for different tumour histological types. Five-year survival with
      occult N2 disease was 35.8% vs. 62.5% without. Median survival was 34 months with
      occult N2 disease vs. 84 months without. Conclusions: With contemporary staging
      techniques, so-called occult N2 disease, even with low volume and PET non-avid
      disease, does not have an indolent course and should still be considered a risk
      factor for poorer prognosis.

PMID- 30233854
TI  - Postoperative chest tube placement after thoracoscopic wedge resection of lung
      for primary spontaneous pneumothorax: is it mandatory?
AB  - Background: The goal of present study is to assess the efficiency and feasibility
      of postoperative care without positioning of chest tube after video-assisted
      thoracoscopic surgery (VATS) in patients with primary spontaneous pneumothorax
      (PSP). Methods: We conducted a prospective randomized trial of patients who have
      undergone video-assisted thoracoscopic wedge resection surgery for PSP. During
      the period of April 2015 until December 2016, 119 eligible patients undergoing
      VATS for PSP were consecutively included. We divided the patients into two groups
      at random: (I) avoiding chest tube (ACT) group, comprising 58 patients in whom
      chest tube was not placed intra or postoperatively, and (II) indwelling chest
      tube (ICT) group, comprising 61 patients in whom chest tube was placed
      conventionally. Primary end point was to evaluate and analyze the postoperative
      clinical data and relevant morbidities between two groups. Results: The mean
      postoperative length of hospital stay (3.57+/-0.79 vs. 5.39+/-0.97 days) and
      postoperative pain (1.37+/-0.78 vs. 2.53+/-0.63) in ACT group were significantly
      lower than in the ICT group (P<0.05). However, there were no statistical
      differences between two groups regarding other clinical data and postoperative
      morbidities. There were no patients who experienced significant adverse events
      postoperatively. Conclusions: Postoperative management without chest tube
      placement is safe and feasible approach for patients undergoing thoracoscopic
      wedge resection for PSP.

PMID- 30233855
TI  - Oxidative damage and DNA damage in lungs of an ovalbumin-induced asthmatic murine
      model.
AB  - Background: Asthma is characterized to chronic airway inflammation. However, the
      role of oxidative damage and DNA damage in the pathophysiology of asthma have
      rarely been studied. On the other hand, there are evidences that DNA-dependent
      protein kinase (DNA-PK) participates in DNA damage repair and regulates innate
      immune responses and proinflammatory signaling pathways. Methods: After ovalbumin
      (OVA)-induced asthmatic murine model was established, airway hyper-responsiveness
      (AHR), total and differential bronchoalveolar lavage fluid (BALF) cell counts. IL
      4, IL-8, IL-13 and TNF-alpha were chosen to evaluate the airway inflammation, and
      oxidative damage indicators levels (8-isoprostane and 8-OhdG) in BALF were
      measured. Alkaline comet assay was conducted to detected DNA damage. Histological
      analysis was conducted after hematoxylin and eosin (HE) straining, and proteins
      were extracted for 3-nitrotyrosine (3-NT) detection and immunoblotting. Results:
      AHR, infiltration of inflammatory cells and pro-inflammatory cytokine levels in
      lungs were significantly higher in asthmatic mice. OVA challenge resulted in
      robust increase in 3-NT, 8-isoprostane and 8OHdG in lungs, which represented
      oxidative damage level. DNA damage and repair proteins levels in asthma were also
      increased. NU7441 aggravated the DNA damage level. However, it suppressed
      infiltration of lung inflammatory cells and inflammatory cytokine levels,
      suggesting that DNA-PK may be a potential target for treatment of allergic
      asthma. Conclusions: Our study showed that oxidative damage and DNA damage
      existed in the airway of asthmatic mice. NU7441 augmented DNA damage level, and
      moreover, it also attenuated infiltration of inflammatory cells and pro
      inflammatory cytokine levels in asthmatic lungs.

PMID- 30233856
TI  - A two-step surgical approach combining sternotomy and subsequent thoracotomy for
      locally advanced lung cancers requiring both right upper lung resection and
      superior vena cava reconstruction.
AB  - Background: Locally advanced lung cancers involving both right upper lung lobe
      and superior vena cava (SVC) requiring both lung resection and SVC reconstruction
      are generally deemed unresectable. However, previous evidence has proved that
      such patients could benefit from surgery if radical resection is achieved.
      Generally, a hemi-clamshell approach is adopted to complete such resection.
      However, it has the limitation of insufficient exposure of posterior mediastinum.
      Therefore, we introduced a two-step surgical approach combining sternotomy and
      thoracotomy for such lung cancers. Methods: A two-step surgical approach
      combining median sternotomy and subsequent posterolateral thoracotomy, via which
      radical lobectomy with systematic lymphadenectomy and SVC reconstruction could be
      successfully achieved, was described. Results: We have performed such surgery via
      the two-step surgical approach combining median sternotomy and subsequent
      posterolateral thoracotomy in five patients from January 2017 to March 2018. All
      those patients achieved radical resection of the lung cancer with lobectomy and
      systematic lymphadenectomy and SVC reconstruction with artificial blood vessels,
      and had an uneventful postoperative recovery without any major complications.
      Conclusions: Our initial experience proved that this two-step surgical approach
      combining median sternotomy and subsequent posterolateral thoracotomy was safe
      and feasible for locally advanced lung cancers requiring both lung resection and
      SVC reconstruction.

PMID- 30233857
TI  - Long-term results after surgical treatment of the dominant lung adenocarcinoma
      associated with ground-glass opacities.
AB  - Background: To evaluate the effect of first-time and eventual reiterative surgery
      on overall survival (OS) and disease-free survival (DFS) in Caucasian patients
      affected by an invasive adenocarcinoma (ADC) with at least another ground-glass
      opacity (GGO). Methods: We analysed 47 patients operated on for lung ADC,
      identified as main cancer (MC), with at least one synchronous GGO, from January
      2003 to March 2017. Characteristics associated with the evolution of GGOs were
      investigated with logistic regression and overall and DFS were evaluated with
      Kaplan-Meier method. Results: Forty-two (89%) patients received an anatomic
      resection of the MC, 5 patients were treated by a single or multiple wedge
      resections. In total, 9 (19.1%) patients had all the lesions resected undergoing
      simultaneous resection of ipsilateral GGOs at first surgery while the remaining
      38 (80.9%) patients still had at least one GGO that was followed up by serial CT
      scan. At the median follow-up of 41 months, GGO evolved in 16 (42.1%) patients.
      The presence of solid component at the initial CT scan was the only risk factor
      for evolution of the GGO. Thirteen patients underwent surgical resection showing
      an invasive ADC in 9 patients, MIA in 3 and AIS in 1. New GGOs developed in 7
      (14.9%) patients, in which three underwent surgery showing the presence of solid
      ADC, MIA and AAH. OS rate at 5 years was 97.4%. DFS at 3 years was 82% and was
      significantly influenced by the stage of MC. Conclusions: Patients affected by an
      invasive ADC with at least another GGO nodule enjoy good OS and DFS with a
      surgical reiterative approach. Part-solid GGO is associated with GGO progression
      requiring treatment, but OS is not influenced by the new onset or evolution of
      GGOs. DFS is affected by the stage of the MC which dictates the treatment
      strategy.

PMID- 30233858
TI  - Neurokinin 1 receptor promotes rat airway smooth muscle cell migration in
      asthmatic airway remodelling by enhancing tubulin expression.
AB  - Background: Airway remodelling is a major contributor to hyper-responsiveness
      leading to chronic asthma; however, the underlying mechanisms remain unclear.
      This study aimed to investigate the effects of a neurokinin 1 receptor (NK1R)
      antagonist (WIN62577) on the migration of airway smooth muscle cells (ASMCs) and
      the expression of NK1R and alpha-tubulin in airway remodelling using young rats
      with asthma. Methods: Sprague-Dawley rats were randomly divided into a control
      group and airway remodelling group. Rats in the model group were stimulated with
      ovalbumin for 8 weeks. Primary ASMCs were cultured and purified from all rats,
      and then treated with different doses of WIN62577. The expression of NK1R and
      alpha-tubulin in ASMCs was assessed using immunofluorescence, real-time
      quantitative polymerase chain reaction, and western blotting. Changes in ASMC
      migration were detected by a transwell chamber assay. Results: The transwell
      assay showed that the number of migrating ASMCs in the asthmatic airway
      remodelling group was significantly greater than that in the control group
      (P<0.01), which was inhibited by WIN62577 in a dose-dependent manner, with peak
      inhibition detected at 10-8 mol/L. The mRNA and protein expression levels of NK1R
      and alpha-tubulin were significantly higher in the asthmatic airway remodelling
      group than in the control group (P<0.05 and P<0.01, respectively), and were
      significantly decreased after treatment with WIN62577 (P<0.01 and P<0.05,
      respectively). Conclusions: NK1R antagonists may suppress ASMC migration in a rat
      model of airway remodelling by inhibiting tubulin expression, indicating a new
      potential target for the treatment and control of chronic asthma.

PMID- 30233860
TI  - An innovative panel to assess endothelial integrity of pedicled and skeletonized
      internal thoracic artery used as aortocoronary bypass graft: a randomized
      comparative histologic and immunohistochemical study.
AB  - Background: Optimal preservation of endothelial integrity of the vessels used as
      aortocoronary grafts is a crucial determinant of long-term clinical success of
      coronary artery bypass grafting (CABG). The purpose of this study was to evaluate
      an impact of two common techniques to harvest left internal thoracic artery
      (LITA) on endothelial integrity. Methods: One hundred twenty consecutive patients
      (84 males and 36 females) with a mean age of 64.9+/-8.8 years undergoing CABG
      were randomized to receive pedicled (group P; n=60) or skeletonized (group S;
      n=60) LITA grafts. During surgery LITA was harvested by the same experienced
      cardiac surgeon. The most peripheral surplus segments of LITA were obtained and
      then analysed histologically under light microscope. Additionally, endothelial
      expression of CD31, CD34, CD133 and nitric oxide synthase (eNOS) were evaluated
      by means of immunohistochemistry. Results: In both groups, no cases of major
      arterial wall damage such as disruption, dissection, thrombosis or subadventitial
      hematoma were noted on LITA cross sections. Immunohistochemical assessment of
      protein expression revealed no differences in endothelial expression of CD133,
      CD34 antigens (markers of regeneration potential) and eNOS (indicating preserved
      functional integrity) between studied groups. Contrary to them, endothelial
      immunoreactivity of CD31, a marker of the morphological integrity of the
      endothelium, was revealed to be stronger in group P. Conclusions: The
      skeletonized method of LITA harvesting may be associated with worse preservation
      of morphological integrity of endothelium but without compromising functional
      integrity and potential for tissue regeneration.

PMID- 30233861
TI  - Comparison of different methods of postoperative analgesia after thoracotomy-a
      randomized controlled trial.
AB  - Background: Continuous thoracic epidural analgesia (TEA) is a preferred method of
      postoperative analgesia in thoracic surgery. Intravenous patient-controlled
      analgesia (IVPCA) may be an effective alternative. One of the most commonly used
      opioids in PCA is morphine. It has high antinociceptive efficacy but is
      associated with many adverse events. Oxycodone can be an alternative. A small
      number of scientific reports comparing morphine and oxycodone in PCA for the
      treatment of acute postoperative pain after thoracotomy was the reason to conduct
      this study. Methods: Prospective, randomised, observational study. In total of 99
      patients scheduled for elective thoracotomy were randomized into three study
      groups. TEA group received continuous TEA as a method of postoperative pain
      management, morphine (MF) group received morphine IVPCA, and morphine (OXY) group
      oxycodone IVPCA. For 48 hours' hemodynamic parameters, level of pain, sedation
      and the need for rescue analgesia were monitored. After 48 hours' patients were
      asked about their satisfaction with pain treatment using Likert scale and
      assessment of opioid related adverse events via overall benefit of analgesia
      score (OBAS). Results: The level of pain in visual analogic score (VAS) and
      Prince Henry Hospital Pain Score (PHHPS) scales was significantly lower in TEA
      group with no significant difference between groups MF and OXY. Using morphine in
      PCA was associated with a significantly higher likelihood of need of rescue
      analgesia. The level of sedation in Ramsay scale was significantly higher in MF
      compared to OXY and TEA group. There were no significant differences between
      groups in OBAS scale. TEA group was characterized by the highest degree of
      patient satisfaction. Conclusions: TEA provided superior anaesthesia compared to
      PCA in our study group. Use of PCA oxycodone in postoperative pain management
      after open thoracotomy provides similar nociception control compared to morphine
      but is associated with less sedation and patients using oxycodone IVPCA require
      smaller doses of rescue analgesia compared to systemic morphine IVPCA.

PMID- 30233859
TI  - Frequency of actionable alterations in epidermal growth factor receptor (EGFR)
      wild type non-small cell lung cancer: experience of the Wide Catchment Area of
      Romagna (AVR).
AB  - Background: Molecular diagnostics for non-small cell lung cancer (NSCLC) has
      become the standard of care for personalized treatment. Epidermal growth factor
      receptor (EGFR) mutation and EML4-ALK translocation represent the two most
      important alterations in first-line treatment decision-making. However, other
      potentially targetable alterations are also present. Methods: One thousand
      consecutive NSCLC patients with EGFR wild type (wt) tumors diagnosed by routine
      molecular analysis were considered. KRAS, BRAF, ERBB2, PIK3CA, NRAS, ALK, MAP2K1,
      RET and DDR2 gene mutations were analyzed using the multiparametric Sequenom
      MassARRAY(r) platform. EML4-ALK and ROS1 rearrangements were also assessed by
      fluorescent in situ hybridization. HER4 status was determined by direct
      sequencing. Results: Three hundred and forty-eight (34.8%), 31 (3.1%), 39 (4.4%),
      14 (1.8%), 6 (0.7%), 16 (1.8%), 5 (0.6%) and 9 (0.9%) patients showed an
      alteration in KRAS, BRAF, ALK, ROS1, NRAS, PIK3CA, MAPK1/2 and HER2 genes,
      respectively. Of the 657 patients for whom all markers were determined, 318 (48%)
      patients had at least one alteration. Eight patients showed overlapping
      mutations, 4 KRAS mutation/EML4-ALK translocation, one KRAS mutation/ROS1
      rearrangement, 2 KRAS/PIK3CA mutations, and one BRAF/PIK3CA mutations.
      Conclusions: About 50% of our patients had a potentially targetable alteration,
      confirming the usefulness of a multiparametric approach for routine molecular
      diagnostics aimed at identifying potential therapeutic targets.

PMID- 30233862
TI  - Management of residual pleural space after lung resection: fully controllable
      paralysis of the diaphragm through continuous phrenic nerve block.
AB  - Background: Residual pleural space after lung resection associated with air leak
      is a challenging issue, potentially causing serious complications. We report a
      new, postoperative technique to reduce the pleural space, inducing a controlled
      and reversible paralysis of the diaphragm. Methods: Ten patients were enrolled (7
      lobectomies, 2 bilobectomy, 1 wedge resection). Inclusion criteria were:
      digitally detected air flow >200 mL/min at post-op day 3, presence of empty
      pleural space at chest x-ray, absence of restrictive lung disease, absence of
      known arrhythmias. A 22G nerve-block catheter was place under ultrasound guidance
      in proximity to the phrenic nerve, between the sternocleidomastoid muscle and the
      anterior scalene muscle at the level of 6th cervical vertebra. Continuous
      infusion of ropivacaine 0.2% 3 mL/h was started. Fluoroscopy was used to confirm
      significant reduction in hemidiaphragm movements. Monitoring of vital signs and
      intense respiratory physiotherapy were enhanced. The infusion was stopped at air
      leak cessation and the catheter was removed along with the chest drain. Results:
      No peri- and post-procedural complications occurred. In all patients, we observed
      an immediate reduction of the empty pleural space and resolution of the air leak
      within few days (3+/-1.16 days). After suspension of local anaesthetic, complete
      restoration of the hemidiaphragm function has been documented. Conclusions: This
      is an effective and minimally invasive method to reduce the residual pleural
      space after lung resections. Narrowing of the pleural space facilitates the
      contact between the lung and the chest wall promoting the resolution of the air
      leak. Diaphragm paralysis is controlled and temporary with no residual
      disabilities.

PMID- 30233863
TI  - Comparison of perioperative and oncological outcomes between video-assisted
      segmentectomy and lobectomy for patients with clinical stage IA non-small cell
      lung cancer: a propensity score matching study.
AB  - Background: Segmentectomy for lung cancer remains controversial because of the
      complexity of the procedure and concern about an increased recurrence rate. It is
      important to compare perioperative and oncological outcomes between segmentectomy
      and lobectomy. Methods: From January 2007 to December 2016, 41 segmentectomies by
      video-assisted thoracic surgery (VATS) and 122 VATS lobectomies for 163 patients
      with clinical stage IA non-small cell lung cancer (NSCLC) were performed.
      Clinicopathological factors, including recurrence rate and survival rate, were
      compared. In order to reduce biases of outcomes, clinicopathological factors were
      used for propensity score matching (PSM). Then, 41 VATS segmentectomies and 41
      lobectomies were selected and further analyzed. Results: No significant
      differences were seen between the two groups in age, pulmonary function,
      comorbidity, operative time, blood loss, chest tube duration days, postoperative
      stay days, complications, histological type, and multiple primary rate. Smoking
      index resected number of nodes, tumor size, lymph node metastasis rate, and
      pathological stage were higher in the lobectomy group than in the segmentectomy
      group (P<0.05). In the lobectomy group, 16 patients (13.1%) had recurrence, and 2
      patients (1.6%) died because of cancer progression. There were no significant
      differences in the recurrence rate and prognosis between the two groups. In
      addition, Cox regression analysis suggested that sex, lymph node metastasis, and
      pathology stage were associated with recurrence (P<0.05), but no factor was an
      independent prognostic factor. After PSM, the two groups had similar
      clinicopathological factors, and the type of operation still had no relationship
      with the recurrence rate or the death rate. Conclusions: Perioperative and
      oncological outcomes of VATS segmentectomy are similar to those of VATS lobectomy
      for patients with clinical stage IA NSCLC. VATS segmentectomy can be considered
      one of the surgical procedures appropriate for patients with clinical stage IA
      NSCLC.

PMID- 30233864
TI  - Assessment of adequacy of intraoperative nodal staging and factors influencing
      the lack of its compliance with recommendations in the surgical treatment of non
      small cell lung cancer (NSCLC).
AB  - Background: Adequate pathological status of lymph nodes sampled during resection
      of NSCLC determines prognosis and decides on further therapeutic actions. The
      areas of analysis are the factors affecting evaluation of pN accuracy, and the
      convergence of recommendations with actual intraoperative sampling of lymph
      nodes. Methods: The data of 3,215 patients with NSCLC consecutively operated with
      the intention of radical resection in 2007-2017, were analyzed. Accuracy of nodal
      sampling and influencing factors were compared with Union for International
      Cancer Control (UICC) guidelines, which recommend that to confirm pN0 status at
      least six lymph nodes/stations free of the disease must be removed. Three should
      be sampled from mediastinum (including subcarinal) and three from N1 stations.
      Results: A significant number of patients were found to have an adequate staging,
      especially after 2009, in terms of recommended quantity of nodes/nodal stations
      (P<0.0001). Age >=64 (P=0.048), left side (P<0.0001), sublobar resection
      (P<0.0001), T1 tumors (P=0.019) are the factors affecting inadequacy of staging.
      Patients with inaccurate staging were found to have a considerably lower pN1
      (7.2% vs.15.9%, P<0.001) and pN2 (9.7% vs.13.4%, P<0.001) status. Survival of
      patients with inadequate staging were found to be significantly worse (P=0.0002),
      which resulted in worse survival of those patients in stage I (P=0.00004), stage
      II (P=0.023) and stage III (P=0.031) of NSCLC. Conclusions: UICC recommendations
      led to an increased adequacy of nodal sampling. The factors affecting
      insufficient number of sampled nodes include advanced age, left side, sublobar
      resections and T1 stage. Inaccuracy of intraoperative nodal staging results in
      incorrect prognosis.

PMID- 30233866
TI  - Application of albumin/globulin ratio in elderly patients with acute exacerbation
      of chronic obstructive pulmonary disease.
AB  - Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD)
      has become an important disease of hospitalized elderly patients, which lack
      simple and inexpensive indicators for evaluating the condition and prognosis.
      This study was performed to investigate the clinical significance of the serum
      albumin/globulin ratio (AGR) in elderly patients with AECOPD. Methods: The data
      of 252 hospitalized elderly patients with AECOPD, 89 stable COPD patients and 115
      elderly healthy individuals were analyzed and compared. The differences in the
      AGR, logarithm of the serum C-reactive protein (LogCRP) level, prealbumin (PA)
      level, and immunoglobulin G (IgG) level were compared. AECOPD patients were
      grouped using the optimal cutoff values of each index to compare the difference
      in the combined infection rate. The correlation between hospital stays and AGR
      was analyzed. Results: The AGR, LogCRP, PA level, and IgG level were different
      among the AECOPD group, stable COPD group and healthy control groups (P<0.05).
      The AGR, LogCRP, and PA level were different (P<0.05) among the Global Initiative
      for Chronic Obstructive Lung Disease (GOLD) I, II, II, and IV groups. Age, AGR,
      LogCRP, and PA level were different (P<0.05) between the infection and non
      infection groups. After grouping according to the optimal cutoff values, the
      combined infection rate was different (P<0.05). The AGR was negatively correlated
      with the hospital stay (r=-0.583, P<0.001). The hospital stay was longer in
      patients with an AGR of <1.37 than >=1.37 (P<0.001). Conclusions: The AGR can be
      regarded as a reference index for evaluating the condition of elderly patients
      with AECOPD, determining the presence of combined infection, and predicting the
      prognosis.

PMID- 30233865
TI  - Predictors and prognosis of left ventricular thrombus in post-myocardial
      infarction patients with left ventricular dysfunction after percutaneous coronary
      intervention.
AB  - Background: We aimed to investigate the predictors and prognosis of left
      ventricular thrombus (LVT) in patients admitted for post-myocardial infarction
      (MI) and left ventricular dysfunction after contemporary percutaneous coronary
      intervention (PCI). Methods: We prospectively enrolled 267 consecutive post-MI
      patients with left ventricular ejection fraction (LVEF) <0.45 based on the
      Shanghai East Hospital PCI database since 2012. Altogether 25 (9.36%) patients
      were selected as the LVT group. Baseline, angiographic, procedural
      characteristics and 1-year clinical outcomes were compared by Chi-square test, t
      test or Kaplan-Meier survival analysis as appropriate. Receiver operating
      characteristic (ROC) curves were plotted for the accuracy of the multivariate
      analysis model. A multiple logistic regression was applied to predict LVT
      formation. Results: The independent risk factors of LVT were left ventricular
      aneurysm [odds ratio (OR): 1.29, 95% confidence interval (CI): 1.09-1.52,
      P<0.01], incomplete revascularization (OR: 0.05, 95% CI: 0.01-0.35, P<0.01),
      SYNTAX score (OR: 1.28, 95% CI: 1.14-1.43, P<0.01) and D-dimer (OR: 1.90, 95% CI:
      1.19-3.04, P<0.01). The SYNTAX score and D-dimer effectively indicated the
      development of LVT with optimal cutoff values of 29.50 and 1.53 mg/L,
      respectively. Patients with LVT had significantly worse outcomes at 1-year
      clinical follow-up, especially higher incidence of ischemic or hemorrhagic
      stroke. Conclusions: This study indicated that the presence of left ventricular
      aneurysm, incomplete revascularization, higher SYNTAX score and D-dimer level
      were the independent predictors of LVT formation in post-MI and LV dysfunction
      patients, which related to worse clinical outcomes. Future studies for early
      intervention and complete revascularization in high-risk subgroup patients are
      expected.

PMID- 30233867
TI  - Diagnostic benefits of the combined use of liquid-based cytology, cell block, and
      carcinoembryonic antigen immunocytochemistry in malignant pleural effusion.
AB  - Background: Malignant pleural effusion (MPE) is a common complication of cancer
      cell metastasis to the pleura. Discrimination between MPE and benign pleural
      effusion is necessary to design treatment strategies. Cytology is important for
      the diagnosis of MPE. Carcinoembryonic antigen (CEA) is an epithelial biomarker
      with a strong staining pattern in adenocarcinomas. Here, the diagnostic
      performances of liquid-based cytology (LBC), cell block (CB) preparation, and CEA
      immunostaining for the detection of malignancy in effusion cytology were compared
      in a large case series. Methods: In a single institution, 1,014 cytology samples
      from 862 patients were retrospectively collected and reviewed between January
      2013 and November 2015. Ethanol-fixed, paraffin embedded CB of pleural effusions
      was analyzed by CEA immunostaining. Diagnostic values were compared among LBC,
      CB, CEA immunostaining, and the combination of two methods. Results: The
      sensitivity and specificity of the CB preparation were 94.3% and 98.7%,
      respectively, compared with 81.3% and 99.4% for LBC preparations, respectively.
      Combination of LBC and CB increased sensitivity by 98.3%. Although the accuracy
      of CEA staining itself was moderate (sensitivity, 89.8%), the combined use of CB
      and CEA tumor marker increased the detection rate of malignancy (sensitivity,
      100%; specificity, 100%), compared with that of cytology (LBC or CB) alone.
      Conclusions: The sensitivity and specificity for the diagnosis of MPE could be
      improved by integrating the CB and CEA staining into LBC in routine clinical
      practice to improve diagnostic accuracy.

PMID- 30233868
TI  - Effect of continuous positive airway pressure therapy on circadian patterns of
      cardiac repolarization in patients with obstructive sleep apnoea: data from a
      randomized trial.
AB  - Background: Obstructive sleep apnoea (OSA) has been proposed as an independent
      risk factor for sudden cardiac death (SCD). This study takes advantage of a
      previous randomized trial and seeks to evaluate circadian patterns of the QTc
      interval, a marker of cardiac repolarization and biomarker for SCD, in patients
      with OSA. We hypothesized that patients with OSA would exhibit longest QTc during
      the night-time and that continuous positive airway pressure (CPAP) therapy would
      reverse this. Methods: One hundred eighteen patients diagnosed with moderate-to
      severe OSA were randomized to receive therapeutic or subtherapeutic CPAP for 4
      weeks. Of these, 84 had full 24 h-Holter monitoring data at baseline and follow
      up. Weighted means of all QTc-intervals were analysed over 24 h, during four time
      periods (12 pm-6 am, 6 am-12 am, 12 am-6 pm, 6 pm-12 pm) as well as during each
      individual hour. A two-sided P value <0.05 was considered to be of statistical
      significance. Results: QTc-intervals at baseline [mean (SD) over 24 h: 407.8 ms
      (36.6)] were highest from 6 pm-12 pm [411.7 ms (42.0)] and shortest from 6 am-12
      am [405.4 ms (39.5)]. Overall 24 h CPAP treatment effect on QTc was -11.3 ms [95%
      confidence interval (CI), -22.1 to -0.6; P=0.039] and was estimated to be greater
      from 6 pm-12 pm than from 12 pm-6 am (P=0.068). The CPAP treatment effect on QTc
      was driven by those patients in the highest QTc decile at baseline (all >430 ms).
      In these patients, CPAP led to reductions in QTc, allowing reclassification into
      lower risk-associated values of QTc (<430 ms). Conclusions: In this exploratory
      study, CPAP treatment led to an overall reduction in the QTc-interval compared
      with subtherapeutic CPAP. This reduction seems more pronounced during evening
      hours and in patients with a QTc above 430 ms.

PMID- 30233869
TI  - Risk factor analysis and management strategies of operating room-related
      infections after coronary artery bypass grafting.
AB  - Background: To investigate and analyze the risk factors of operating room-related
      infections after coronary artery bypass grafting (CABG), to propose corresponding
      infection control management strategies, and to verify and evaluate the
      effectiveness of the strategy implementation. Methods: Patients with coronary
      heart disease who underwent CABG in a hospital from January 2015 to December 2016
      were selected for inclusion in this study. The following patient variables were
      documented: demographics, history of underlying diseases (hypertension and
      diabetes), preoperative American Society of Anesthesiologists (ASA) score, skin
      preparation method, perioperative use of antibiotics, operation duration,
      intraoperative hypothermia, intraoperative blood loss, intraoperative blood
      transfusion, presence of visitors in the operating room, consecutive use of the
      same operating room, qualification of the surgeon, and surgical site infection.
      The infection diagnosis was confirmed using the Diagnostic Criteria for
      Nosocomial Infections (Trial) issued by the Ministry of Health in 2001.
      Univariate chi-square tests and multivariate logistic regression analysis were
      used to analyze the risk factors for infection in patients undergoing CABG, and
      infection control management strategies were proposed. The proposed infection
      control strategies were applied to patients who underwent CABG in the hospital in
      2017. The effectiveness of the strategy implementation was evaluated. Results: We
      analyzed in 139 patients (417 coronary artery bypass grafts from January 2015 to
      December 2016) and identified 4 surgical site infections. The incidence of
      infection was 2.88%. According to the univariate analysis, the following factors
      were related to the high incidence of surgical site infections: advanced age,
      history of underlying diseases (hypertension and diabetes), obesity, ASA score
      (class II or above), conventional skin preparation method, irrational
      perioperative antibiotic use, operation duration >4 hours, presence of visitors
      in the operating room, and consecutive use of the same operating room (P<0.05 for
      all variables). Multivariate logistic regression analysis showed that advanced
      age, history of underlying diseases (hypertension and diabetes), irrational
      perioperative antibiotic use, operation duration >4 hours, and presence of
      visitors in the operating room were high risk factors for surgical site infection
      after CABG. From January 2017 to December 2017, after applying the proposed
      infection control measures to patients undergoing CABG, the surgical site
      infection rate was 1.13% (3/266), which was significantly different from that of
      the previous period (P<0.05). Conclusions: The following are high risk factors
      for surgical site infection after CABG: advanced age, history of underlying
      diseases (hypertension and diabetes), irrational antibiotic use during the
      perioperative period, operation duration >4 hours, and presence of visitors in
      the operating room. Medical providers should fully understand these risk factors
      and optimize the adjustable factors during the perioperative period to minimize
      the incidence of infections after CABG.

PMID- 30233870
TI  - Critical care medicine in Taiwan from 1997 to 2013 under National Health
      Insurance.
AB  - Background: Monitoring of trends in the use of the intensive care unit (ICU) and
      the outcomes of ICU patients is essential for the assessment of the effective use
      of ICU. This study aims to investigate the incidence and outcome of critical care
      admissions in Taiwan from 1997 to 2013. Methods: Patients >18 years who had ICU
      admission between January 1997 and December 2013 were identified from the
      National Health Insurance Research Database in Taiwan. The main outcomes
      including ICU mortality and ICU length of stay (LOS) were measured. Results: A
      total of 3,451,157 patients with ICU admission were identified during the study
      period. The mean ICU LOS was 5.9+/-9.0 days and the overall ICU-mortality rate
      was 19.8%. The mean age of the patients was 65.4 years old, 58.0% were elderly
      (>=65 years old), 61.1% were male. Annual incidence of ICU admissions increased
      from 115,754 in 1997 (age-adjusted incidence: 1,130/100,000 population) to
      244,820 in 2013 (incidence: 1,483/100,000 population) (P<0.0001). The admission
      rate was highest for patients 75-104 years old (8,074 per 100,000 population),
      and lowest for those 18-44 years old (298 per 100,000 population). Among ICU
      admission patients, the percentage of patients >=75 years old significantly
      increased from 25.2% in 1997 to 38.3% in 2013 (P<0.0001). ICU LOS remained stable
      during the study period, but the annual mortality rate significantly decreased
      from 23.0% in 1997 to 16.3% in 2013. Conclusions: ICU admissions significantly
      increased from 1997 to 2013, especially for elderly patients, in contrast, the
      mortality rate of ICU patients significantly declined with time. In addition, the
      ICU LOS did not change during the study period.

PMID- 30233871
TI  - Value of cardiac biomarker measurement in the differential diagnosis of
      infiltrative cardiomyopathy patients with preserved left ventricular systolic
      function.
AB  - Background: This study aimed to explore the value of cardiac biomarker [serum
      high sensitive troponin T (hs-TNT) and N-terminal pro-brain natriuretic peptide
      (NT-proBNP)] measurement in the differential diagnosis of infiltrative
      cardiomyopathy patients [Friedreich's ataxia (FA), Fabry disease (FD) and light
      chain (AL) cardiac amyloidosis (CA)] with preserved left ventricular (LV)
      systolic function. Methods: Between 2012 and 2014, all consecutive patients
      presenting at our center with infiltrative cardiomyopathy and concomitant
      symmetrical LV hypertrophy as well as preserved LV systolic function were
      included in this study. Serum hs-TNT and NT-proBNP, morphologic and functional
      features derived from echocardiography and cardiac magnetic resonance imaging
      (cMRI) examinations were compared among these patients. Results: A total of 57
      patients (FA 20, FD 23 and CA 14) were included. Hs-TNT and NT-proBNP levels were
      significantly higher in the CA group [median: hs-TNT 98 pg/mL, NT-proBNP 4,110
      pg/mL] than in the FA group [hs-TNT 14 pg/mL, NT-proBNP 40 pg/mL] and FD group
      [hs-TNT 18 pg/mL, NT-proBNP 131 pg/mL, both P<0.001]. There was a negative
      correlation between NT-proBNP and estimated glomerular filtration rate (eGFR) in
      CA patients (r=-0.72, P=0.012). Both hs-TNT >60 pg/mL (sensitivity 0.79,
      specificity 0.93) and NT-proBNP >1,000 pg/mL (sensitivity 0.91, specificity 0.93)
      excellently differentiated CA from FA and FD. Conclusions: Increased hs-TNT and
      NT-proBNP levels are suggestive of CA diagnosis among patients with infiltrative
      cardiomyopathy and preserved LV ejection fraction.

PMID- 30233872
TI  - Cyberknife(r) stereotactic radiation therapy for stage I lung cancer and
      pulmonary metastases: evaluation of local control at 24 months.
AB  - Background: CyberKnife(r) stereotactic radiotherapy allows for minimally invasive
      treatment with satisfactory results in patients with inoperable primary or
      metastatic lung cancer. The objective of this study was to identify factors
      influencing the probability of local control. Methods: Ninety-five patients (100
      lung tumors) treated between January and December 2013 at our department by SBRT
      (stereotactic body radiation therapy) using CyberKnife(r) were included in the
      study. There were 71 stage T1 or T2 primary tumors and 29 secondary tumors. The
      tracking methods were as follow: fiducial markers with Synchrony(r) in 50 cases
      (gold seeds in 35, coils in 15 cases), spine with 4D-CT and Xsight(r) Spine in 43
      cases, and direct viewing by Xsight(r) Lung in 7 cases. The methods were
      allocated according to the characteristics of each target. Results: With a median
      follow-up of 24 months, the probability of local control at 24 months was 88%.
      The probability of local control differed according to the size of the target
      (92% for tumors <=35 mm and 54% for tumors >35 mm: P=0.013) and according to the
      distance of the fiducial markers in relation to the target (95% when <50 mm and
      69% when >=50 mm: P=0.011). Conclusions: The best results were obtained with
      small lesions. With Synchrony(r), the distance of the target relative to the
      fiducial markers should be less than 50 mm. Gold seeds are recommended, although
      coils may be used instead of gold seeds. The number of fiducial markers did not
      have a significant impact on the probability of local control. With an
      appropriate tracking method, stereotactic radiotherapy is an efficient treatment
      for stage I lung cancer and lung oligometastases.

PMID- 30233873
TI  - Impact of the introduction of thoracoscopic lobectomy for non-small cell lung
      cancer: a propensity score-matched analysis.
AB  - Background: The present study evaluated the impact of the introduction of
      thoracoscopic lung lobectomy (TL) for non-small cell lung cancer at our
      institution. Methods: This study retrospectively compared surgical and
      oncological outcomes in the period before and after the introduction of TL for
      non-small cell lung cancer. Propensity score-matched analysis was performed with
      respect to baseline patient variables and tumor characteristics. Results:
      Patients were divided into two groups: those who underwent lung lobectomy in the
      period before (BI group, n=261) and after (AI group, n=261) the introduction of
      TL. The proportion of TLs at our institution increased from 1.3% in the BI group
      to 93% in the AI group. The AI group experienced a longer duration of surgery,
      lesser intraoperative blood loss, and a significantly shorter postoperative
      hospital stay (POHS). There were no significant differences in postoperative
      complications between the two groups. The median follow-up period was 50 months
      in both groups. No significant differences were observed between the BI and AI
      groups with respect to 5-year overall survival (OS) (76.1% and 71.7%,
      respectively; P=0.1973) and disease-free survival (DFS) (67.6% and 66.1%,
      respectively; P=0.4071). On multivariate analysis, pathological N1-2 status was
      an independent predictor of survival. AI group and TL showed no independent
      association with survival. Conclusions: The introduction of TL represented a
      positive change at our institution owing to decreased invasiveness and
      oncological equivalence of the surgical treatment for non-small cell lung cancer.

PMID- 30233874
TI  - Discrepancies between ALK protein disruption and occurrence of ALK gene
      rearrangement in Polish NSCLC patients.
AB  - Background: Non-small cell lung cancer (NSCLC) patients with epidermal growth
      factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK)
      rearrangement are predisposed to molecularly targeted therapies. Proper
      diagnostic is crucial for quick and correct patients qualification to optimal
      treatment method. Genetic tests to detect predictive factors could be performed
      sequentially. After excluding EGFR mutations, abnormal ALK protein expression
      should be tested using immunohistochemistry (IHC) method. In patients with
      disrupted ALK expression, the rearrangement of the ALK gene should be confirmed
      by FISH method. Despite few years of experience in analysis of these predictive
      factors, there are still problems in interpretation of diagnostic tests results.
      Especially, some recommendations for ALK IHC diagnosis are not precise. Methods:
      Mutations in EGFR gene were examined using real-time PCR technique in 1,108
      formalin-fixed paraffin-embedded (FFPE) tissues, 398 FFPE cell-blocks and 470
      cytological specimens of NSCLC. The disrupted ALK protein expression was analysed
      in 1,100 samples including 782 histological and 306 cytological (cell-blocks)
      samples using IHC. Twelve materials (1.1%) were non-diagnostic in IHC. ALK gene
      rearrangement using FISH method was analysed in IHC positive cases. Results: The
      frequency of EGFR mutations was 8.6%. EGFR mutations occurred significantly more
      often in females (P=0.00001, chi2=62.732) and in adenocarcinoma cases (P=0.0002,
      chi2=14.222). The exon 19 deletions (49%) and exon 21 Leu858Arg substitution
      (38%) were the most common, rare EGFR mutations occurred in 13% of patients. Any
      expression of abnormal ALK protein was detected in 202 cases (18.57%). ALK gene
      rearrangement was confirmed in 49 cases (4.5%). ALK gene rearrangement is
      significantly more common in female than in male (P=0.0105, chi2=6.541). In
      patients with ALK gene rearrangement, the median percentage of nuclei with ALK
      rearrangement was only 25.5%. The polysomy (>=4 gene copy number per nuclei) of
      ALK gene was observed in 39 cases (21.4% of patients with diagnostic result of
      FISH examination). Median number of ALK gene copy per nuclei was 2.9+/-0.77.
      Significant positive correlation between percentage of cells with abnormal ALK
      expression in IHC test and percentage of nuclei with ALK rearrangement in FISH
      method was detected (R=0.617, P<0.00001). Significant negative correlation
      between the number of copies of ALK gene and the percentage of cells with
      expression of abnormal ALK was observed (R=-0.2004, P<0.05). ALK gene
      rearrangement was significantly more frequently observed in the material with
      coarse-grained cytoplasmic and membranous IHC staining than in materials with
      light cytoplasmic stippling. The occurrence of cytoplasmic stippling correlated
      with the increase of ALK gene copy number. Conclusions: We indicated that
      diagnosis of ALK disruption in NSCLC patients should be notably careful using IHC
      and FISH methods. Recommendations for ALK diagnosis should include the way of
      interpretation of cases with low percentage of cells with abnormal ALK protein
      expression in IHC test, character of IHC reaction, and cases with ALK gene
      polysomy in FISH method.

PMID- 30233876
TI  - Clinical outcome and risk factors for complications after pulmonary segmentectomy
      by video-assisted thoracoscopic surgery: results of an initial experience.
AB  - Background: Pulmonary anatomical segmentectomies are increasingly being done via
      video-assisted thoracoscopic surgery (VATS). We analyzed clinical outcomes and
      risk factors for post-operative complications after pulmonary segmentectomy by
      VATS was introduced in two institutions. Methods: We retrospectively reviewed
      records of all patients who underwent anatomical pulmonary segmentectomy by VATS
      from 2014 to 2016 at the university hospitals of Geneva and Lausanne in
      Switzerland. Results: One hundred twenty-nine patients (64 men; median age 68
      years, range, 29-85 years) underwent anatomical VATS segmentectomy for primary
      lung tumors (n=100), metastases (n=16) and benign lesions (n=13). The overall 30
      day mortality and morbidity rates were 0.8% and 31%, respectively. The
      reoperation rate was 4.7% [indications: hemothorax 2, prolonged air leak (PAL) 2,
      segmental torsion 1, empyema 1]. Chest drainage lasted for a median of 2 days
      (range, 1-33 days) and patients were discharged from the hospital after a median
      of 6 days (range, 2-37 days). Postoperative complications were mainly associated
      with chronic obstructive pulmonary disease (COPD) [odds ratio (OR) 2.54 and 95%
      confidence interval (95% CI), 1.18-5.47], and smoking pack-years >50 units (OR
      5.27; 95% CI, 1.68-16.55). Nine patients (9%) presented with distant recurrences.
      Nodule size >2 cm was associated with decreased disease-free survival (DFS)
      (P=0.04). There was no association between surgical experience in VATS
      segmentectomy and DFS or postoperative complications. Conclusions:
      Segmentectomies can be safely performed by VATS in an initial experience and
      result in favorable clinical outcome. COPD and smoking pack-years are associated
      with an increased risk of complications.

PMID- 30233875
TI  - Incidence and risk of thromboembolism associated with bevacizumab in patients
      with non-small cell lung carcinoma.
AB  - Background: Bevacizumab, a recombinant humanized monoclonal antibody against
      vascular endothelial growth factor (VEGF), is effective for the treatment of
      advanced non-small cell lung cancer (NSCLC). However, severe adverse events (AEs)
      have been reported in NSCLC patients treated with bevacizumab. Currently, the
      contribution of Bevacizumab to thromboembolism is still controversial. We
      conducted a study to determine the overall risk and incidence of thromboembolism
      with bevacizumab in NSCLC patients. Methods: Electronic databases such as the
      PubMed, Web of Science and Cochrane Library were searched for related trials.
      Statistical analyses were conducted to calculate the overall incidence rates,
      odds ratios (ORs), and 95% confidence intervals (CIs) by using either random
      effect or fixed-effect models depending on the heterogeneity. We also used trial
      sequence analysis (TSA) to verify the pooled result. Results: A total of 3,555
      subjects from nine studies were included. The overall incidence of
      thromboembolism events in NSCLC patients treated with bevacizumab was 4.8% (95%
      CI: 1.9-7.7%). Without bevacizumab, this incidence was 2.9% (95% CI: 0.6-5.1%).
      Bevacizumab use was associated with a significantly increased risk in
      thromboembolism events (OR =1.74; 95% CI: 1.15-2.62; P=0.008). Subgroup analysis
      based on the doses showed that bevacizumab administered at 15 mg/kg (OR =1.81;
      95% CI: 1.14-2.86; P=0.012), but not 7.5 mg/kg (OR =1.32; 95% CI: 0.78-2.24;
      P=0.296), increased the risk of thromboembolism. Conclusions: Bevacizumab is
      associated with a significantly increased risk of thromboembolism development in
      NSCLC patients. It may have dose-toxicity relationship and low dose of
      bevacizumab may be a better choice for NSCLC patients, with equal efficacy and
      low hazard of thromboembolism events.

PMID- 30233878
TI  - Comparison of the 11th Japanese classification and the AJCC 7th and 8th staging
      systems in esophageal squamous cell carcinoma patients.
AB  - Background: Although the American Joint Committee on Cancer (AJCC) staging system
      has been used worldwide for esophageal squamous cell carcinoma (ESCC), another
      staging system has been proposed by Japanese surgeons. The two systems have
      different lymph node maps, N staging, and stage grouping. This retrospective
      study compared the predictive ability of these two staging systems for survival.
      Methods: We retrospectively reviewed records for 143 patients who underwent
      esophagectomy and mediastinal lymphadenectomy for ESCC from January 2006 to July
      2015. Patients were staged by 7th, 8th AJCC stage and 11th Japanese
      classification. The concordance indexes (C-indexes) of these staging systems were
      compared. Results: Mean age was 63.14+/-8.10 years with 131 (91.6%) men. Median
      follow-up was 47.73 (6.27-134.40) months. All patients received R0 resection.
      Recurrences developed in 30 (20.9%) patients. Both AJCC N staging and Japanese N
      staging well predicted disease-free survival (DFS) (P<0.001). Stage groupings of
      AJCC 7th and 8th and Japanese 11th classification also predicted DFS well
      (P<0.001). The c-index was 0.755 (95% CI, 0.650-0.860) for AJCC N staging and
      0.734 (0.634-0.835) for Japanese N staging (P=0.11). The c-index was 0.813 (0.732
      0.896) for AJCC 7th stage grouping, 0.805 (0.726-0.885) for AJCC 8th, and 0.837
      (0.766-0.908) for Japanese stage grouping. The C-index for the Japanese stage
      grouping was slightly higher than for AJCC, but differences were not significant.
      Conclusions: Both N staging and stage grouping for the 11th Japanese
      classification and 7th and 8th AJCC staging for ESCC showed similar predictive
      power for DFS. Both systems could be applied in clinical situations.

PMID- 30233877
TI  - Pulmonary mechanics and gas exchange characteristics in uncommon etiologies of
      acute respiratory distress syndrome.
AB  - Background: Common causes of acute respiratory distress syndrome (ARDS) include
      pneumonia, aspiration, non-pulmonary sepsis and trauma. Little is known about
      pulmonary mechanics and gas exchange in less-common etiologies of ARDS, which
      comprises 12-23% of cases. Our hospital's ARDS quality assurance database
      contained a substantial number of these cases. This descriptive study examines
      the pulmonary mechanics, and gas exchange characteristics of this diverse cohort
      of ARDS subjects. Methods: Between March 2010 and April 2017 we identified 94
      subjects with less common etiologies of ARDS who had dead space fraction (VD/VT)
      and respiratory system compliance (CRS) measured within 24 hours of ARDS onset;
      86 of whom did not have sepsis as a co-diagnosis. There were 18 identifiable
      sources of ARDS. For descriptive purposes these were subsumed under 10 etiologic
      categories: pancreatitis (n=16), hemorrhagic shock/reperfusion injury (n=9),
      transfusion-associated acute lung injury (TRALI) (n=3), drug overdose (n=13),
      inhalation injury (n=10), idiopathic (n=10), neurogenic (n=8), pulmonary toxicity
      (n=3), hyper-immune response (n=4), hepatic failure (n=7), and 3 other cases: 2
      cutaneous burns and one case of malaria. VD/VT was measured using the Enghoff
      Bohr equation. Arterial blood gases were drawn simultaneously with mixed expired
      CO2 using volumetric capnography and standard pulmonary mechanics measurements.
      Data are expressed as median (IQR). Comparisons between groups used Kruskal
      Wallis and Dunn's post-tests, Mann-Whitney tests or Fisher exact tests. Results:
      The majority of less common ARDS were from indirect sources (79%) with 9%
      attributed to direct causes and 11% idiopathic. Because of the small sample
      sizes, there were no differences in pulmonary mechanics or gas exchange between
      subgroups classified as indirect, direct and idiopathic, or between subgroups
      sharing common lung injury mechanisms. Nevertheless, salient trends were apparent
      particularly in CRS and VD/VT. CRS was most severely reduced in the toxicity
      subgroup and least impaired in the idiopathic subgroup [18 (11 to 22), and 40 (30
      to 43) mL/cmH2O respectively]. VD/VT was extraordinarily high in the hepatic
      failure subgroup and lowest in pancreatitis [0.78 (0.57 to 0.79) and 0.54 (0.47
      to 0.65) respectively]. There was less distinction in oxygenation as median
      values for all subgroups met moderate ARDS criteria. For the entire cohort, only
      VD/VT was statistically different between non-survivors and survivors: 0.66 (0.57
      to 0.78) vs. 0.59 (0.51 to 0.68), P=0.012. Conclusions: Within a diverse cohort
      having less common presentations of ARDS, there was apparent variability in the
      distribution of CRS, VD/VT compared to differences oxygenation dysfunction.
      Elevated pulmonary dead space still identified patients with higher mortality, as
      is the case with more common causes of ARDS.

PMID- 30233879
TI  - Neutrophil gelatinase-associated lipocalin as a complementary biomarker for the
      asthma-chronic obstructive pulmonary disease overlap.
AB  - Background: There is no standardized definition of the asthma-chronic obstructive
      pulmonary disease (COPD) overlap (ACO). Although the blood eosinophil count is
      regarded as a biomarker for identifying ACO, it has no distinct value. This study
      aimed to measure plasma levels of neutrophil gelatinase-associated lipocalin
      (NGAL), a potential biomarker for distinguishing between ACO and non-ACO COPD.
      Methods: We used the Korean cohort in the COPD in dusty area (CODA) study which
      included 137 subjects with COPD confirmed by spirometry. We defined ACO by a
      positive bronchodilator response (forced expiratory volume in 1 s, FEV1 >12% and
      >200 mL from baseline) or based on a previous history of asthma. Plasma levels of
      NGAL were determined by enzyme immunoassay. Results: Among the 137 subjects, 77
      were ACO and 60 were non-ACO COPD. Overall, the plasma NGAL levels were 15.9+/
      7.9 and 15.6+/-6.6 ng/mL for non-ACO and ACO subjects respectively, and not
      significantly different. However, NGAL levels were significantly higher in female
      subjects with ACO (17.0+/-6.4 vs. 11.1+/-4.5, P=0.01). In female subjects, NGAL
      levels showed a good predictive ability to discriminate between ACO and non-ACO
      COPD [area under the receiver operating characteristic curve (AUROC), 0.77]; the
      predictive ability was similar to that of the blood eosinophil count (AUROC,
      0.79). There was a higher probability of discriminating ACO from non-ACO among
      subjects in the highest tertile of NGAL levels (odds ratio, 1.72; 95% confidence
      interval, 0.69-4.28; P for trend =0.01). Conclusions: NGAL levels were
      significantly higher in ACO compared to non-ACO COPD in female subjects. After
      adjusting for gender as a confounding factor, the ability to distinguish ACO was
      better at higher levels of NGAL.

PMID- 30233880
TI  - CO2 during single incisional thoracoscopic bleb resection with two-lung
      ventilation.
AB  - Background: CO2 insufflation could provide a better surgical field during single
      incision thoracoscopic surgery (SITS) with small tidal two-lung ventilation (ST
      TLV). Here we compared the surgical field and physiological effects of ST-TLV
      with and without CO2 during SITS. Methods: Patients underwent scheduled SITS
      bullectomy. Surgery under ST-TLV general anesthesia performed without CO2 (group
      NC) or with CO2 insufflation (group C). The surgical field was graded at
      thoracoscope introduction and at bulla resection as follows: good (more than half
      of the 1st rib visible; bleb easily grasped with the stapler), fair (less than
      half of the 1st rib visible; some manipulation needed to grasp the bleb with the
      stapler), or poor (1st rib non-visible; bleb ungraspable). Vital signs, arterial
      blood gas analysis (ABGA), and mechanical ventilation parameters, postoperative
      chest tube indwelling duration, length of hospital stays, and complications were
      recorded. Results: A total of 80 patients were ultimately included. The surgical
      field at thoracoscope introduction was better in group C (P=0.022). However, at
      bleb resection, the surgical fields did not differ (P=0.172). The operation time
      was significantly longer in group C (P=0.019) and anesthesia recovery time was
      not different (P=0.369). During the CO2 insufflation, the airway pressure was
      higher in group C (P=0.009). Mean PaCO2 was significantly higher (P=0.012) and
      mean PaO2 was significantly lower (P=0.024) in group C, but both values were
      within the physiologically normal range. Postoperative chest tube indwelling
      duration and length of hospital stays were not statistically different (P=0.234
      and 0.085 respectively). Postoperative complication frequencies were similar
      (12.5% for group NC, 10.0% for group C, P=0.723). Conclusions: SITS with CO2
      insufflation during ST-TLV did not produce a superior surgical field except at
      the beginning of surgery. CO2 insufflation required more time and resulted in
      higher mean PaCO2 and peak airway pressure.

PMID- 30233881
TI  - Pure red cell aplasia associated with thymoma: a report of a single-center
      experience.
AB  - Background: Pure red cell aplasia (PRCA) associated with thymoma is relatively
      rare, and relevant reports are limited. We investigated the clinical features and
      outcomes of PRCA associated with thymoma in this study. Methods: A retrospective
      review of all PRCA patients who underwent surgical resection of thymoma from
      April 1, 2004, to December 31, 2015, was performed. Results: We experienced eight
      patients with PRCA among 146 patients who underwent surgical resection of
      thymoma. Extended thymectomy (n=4) and thymectomy (n=4) were performed for
      thymoma. Regarding the WHO classification of thymoma, the subtypes were type B2
      or B3 in seven patients, and the stage of thymoma was advanced in seven patients.
      Complete resection was achieved macroscopically in only five patients. Recurrence
      of thymoma occurred in four patients who underwent complete resection. PRCA was
      diagnosed after surgical resection of thymoma in six patients (range 1-101
      months, median 56.5 months). Cyclosporine was used for PRCA in six patients.
      Pneumonia of treatment-related complications due to cyclosporine occurred in all
      patients. The follow-up period ranged from 13-147 months (median 54.5 months)
      after the PRCA diagnosis. Three patients obtained complete remission of anemia by
      cyclosporine. Although one patient was able to stop taking cyclosporine because
      of complete remission of anemia, transfusion was needed due to relapse of PRCA.
      Five patients died, with the main causes of death diagnosed as pneumonia (n=4)
      and cardiac failure (n=1). Conclusions: PRCA associated with thymoma was
      diagnosed postoperatively in three-quarter of patients. We should be alert for
      the occurrence of PRCA even after resection of thymoma, especially in patients
      with incomplete resection or advanced disease. Cyclosporine was effective for
      PRCA, but treatment-related complications occurred, particularly pneumonia. As
      treatment for PRCA associated with thymoma and its complications were combined in
      a complex manner, treating PRCA associated with thymoma can be quite difficult.

PMID- 30233882
TI  - Prototype of extracorporeal membrane oxygenation (ECMO) therapy simulator used in
      regional ECMO program.
AB  - Background: Simulation is widely accepted as an important tool in training and
      educating healthcare providers. The first regional polish extracorporeal membrane
      oxygenation (ECMO) program called "ECMO for Greater Poland" was recently started.
      Methods: We present a prototype for ECMO prepared for high-fidelity medical
      simulation in extracorporeal life support. ECMO therapy is a complex, difficult
      and expensive therapy in patient care. We have constructed an advanced ECMO
      simulation prototype, which can be used as a training tool in scenarios that
      prepare for real-life experiences. The "ECMO for Greater Poland" program uses
      high-fidelity simulation as a superior tool to simulate several complex clinical
      scenarios, and consequently train healthcare providers in rare, complicated and
      expensive procedures. The training course is standardized and allows repeatable
      training, improvement of skills, and an objective verification of trained skills.
      Results: The ECMO simulation prototype is designed to replicate the physiological
      circulatory system and simulate several scenarios (i.e., bleeding, low pressure,
      occlusion, reaction for proper and incorrect pharmacological treatment). The
      electronic core control unit (CCU) with silicone tubes, artificial vessels
      (modified polyethylene) and analog components can be connected to an ECMO machine
      to emulate the human body during an ECMO simulation. If necessary, damaged and
      used parts can easily be replaced. The total cost of the simulator is
      approximately 450 and 50 USD for disposable parts. Conclusions: This newly
      developed advanced ECMO simulation prototype was recently introduced into
      education and regularly training of healthcare providers of the "ECMO for Greater
      Poland" program. The simulation based training program is financially affordable
      and enables clinical teaching in a wider range of clinical scenarios. The ECMO
      simulation prototype consequently improves level of expertise of the healthcare
      providers and finally improves quality in patient care.

PMID- 30233883
TI  - Serum microRNAs improving the diagnostic accuracy in lung cancer presenting with
      pulmonary nodules.
AB  - Background: MicroRNA (miRNA) is an approach for early diagnosing of cancer. We
      validated a panel of miRNAs (hsa-miR-199a-3p, hsa-miR-148a-3p, hsa-miR-210-3p,
      hsa-miR-378d and hsa-miR-138-5p) to aid early diagnosis of lung adenocarcinoma by
      blood test in lung cancer presenting with pulmonary nodules. Methods: A total of
      369 individuals who were detected pulmonary nodules by computed tomography (CT)
      scan were enrolled into this study. These patients included 274 pulmonary
      malignant or borderline lung diseases and 122 lung benign pulmonary nodules. When
      the lung nodules were detected by combining with CT scan, we got patient blood
      samples in 2 days. Patients' serum was collected within 2 days prior to miRNAs
      analyses. We performed miRNAs panel by reverse transcription-polymerase chain
      reaction (RT-PCR). Results: The sensitivity of miRNAs panel was 34.0% and the
      specificity of miRNAs panel was 90.2%. In invasive adenocarcinoma, the
      sensitivity of miRNAs panel was 44.7%. The overall false positive rate of CT
      imaging for nodules and glass ground nodules (GGNs) was 33.1%. When miRNAs panel
      test positive patients combined with the nodule size, the false positive rate was
      decreased to 3.2%. Conclusions: The greatest impact of using the miRNAs panel CT
      scan was decreasing the false positive. miRNAs panel can improve the diagnosis of
      lung cancer presenting with nodules combined with CT.

PMID- 30233884
TI  - Body mass index of patients with chronic obstructive pulmonary disease is
      associated with pulmonary function and exacerbations: a retrospective real world
      research.
AB  - Background: Chronic obstructive pulmonary disease (COPD) is prevalent in China.
      The role of body mass index (BMI) in COPD progression and prognosis is unclear.
      We analyzed the association between BMI and pulmonary function, inflammation
      levels and exacerbation in Chinese COPD patients. Methods: Our retrospective real
      world research included 744 patients with COPD diagnosed by spirometry and
      hospitalized from January 1st, 2014 to December 31st, 2016. The indicators were
      gathered from hospital records database and frequency of exacerbation in the
      three years were followed up. All 744 patients were divided into four groups by
      BMI grades. We analyzed the association between BMI and pulmonary function,
      inflammation levels and exacerbation by Spearman bivariate correlations, Kruskal
      Wallis test, Mann-Whitney U test and logistic regression. Results: The singly
      proportion (median of BMI) of these patients in underweight, normal weight,
      overweight and obesity was 7.80% (17.54), 45.97% (22.12), 27.96% (27.00) and
      18.28% (31.25) respectively. With increasing of BMI grades, the values of forced
      expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), forced
      expiratory flow (FEF25/50/75) and diffusing capacity of carbon monoxide (DLCO)
      were correspondingly increasing; the percentage of neutrophils and C-reactive
      protein (CRP) presented significant declining trend while the trend of the
      percentage of eosinophils was negative; the dose of systemic corticosteroid and
      length of stay present decreasing tendency; the frequency of exacerbation and
      hospitalization were decreasing. These were similar results in gender, smoking
      status COPD subgroups. Conclusions: In our study, BMI was moderately correlated
      with pulmonary function positively and exacerbations negatively. To some extent,
      BMI might be a useful indicator to predict the prognosis of COPD patients and for
      long-term management.

PMID- 30233886
TI  - Electromagnetic navigational bronchoscopy for diagnosing peripheral lung lesions
      in lung transplant recipients: a single-center experience.

PMID- 30233885
TI  - Learning curve for uniportal video-assisted thoracoscopic surgery lobectomy
      results from 120 consecutive patients.
AB  - Background: Uniportal video-assisted thoracoscopic surgery (VATS) is considered a
      technically demanding procedure. The learning curve, which directly influences
      the adoption of uniportal VATS, has not been described. In this study, we aimed
      to describe the learning curve for uniportal VATS lobectomy from our single
      center's experience. Methods: Uniportal VATS lobectomy was started in October
      2013 in Zhongshan Hospital, Fudan University. Since then, a total of 120
      consecutive patients who underwent uniportal VATS lobectomy were retrospectively
      enrolled. Surgical videos were reviewed to determine the operation time, to which
      cumulative sum (CUMSUM) method was applied to evaluate the learning phases of the
      procedure. Accordingly, patients' clinical features in different phases were
      collected and compared to determine the learning curve for uniportal VATS
      lobectomy. Results: Among the 120 consecutive patients reviewed from October 2013
      to September 2014, the CUMSUM curve showed its inflection at patient number 44:
      the first 30 patients were in the ascending phase, the second 30 patients were in
      the plateau phase, and the remaining patients were in the descending phase.
      Comparable CUMSUM results were recorded both from upper and not-upper lobectomy.
      Intra-operatively, more repeated stapler attempts (73% versus 13% and 5%,
      P<0.001) and higher conversion rate (17% versus 7% and 2%, P=0.028) were recorded
      in ascending phase vs. the plateau phase and descending phase, respectively. Post
      operatively, the morbidity, mortality and the length of hospital stay were
      similar before and after the learning curve cases. Conclusions: In a center with
      conventional VATS experience, the learning period of uniportal VATS lobectomy was
      characterized by repeated stapler attempts, and the volume requirements would be
      approximately 30 cases to reach the performance plateau. Upper lobectomy seemed
      not more difficult to learn than lower or middle lobectomy in uniportal VATS.

PMID- 30233887
TI  - Design variations in vertical muscle-sparing thoracotomy.

PMID- 30233888
TI  - Video-assisted thoracic surgery double sleeve bilobectomy of right upper and
      middle lobes.

PMID- 30233889
TI  - Esophageal cancer patients' information management: cross-cultural differences
      between Dutch and Italian patients in perceived quality of provided oncological
      information.

PMID- 30233890
TI  - Extracorporeal support, during and after lung transplantation: the history of an
      idea.
AB  - During recent years, continuous technological innovation has provoked an increase
      of extracorporeal life support (ECLS) use for perioperative cardiopulmonary
      support in lung transplantation. Initial results were disappointing, due to ECLS
      specific complications and high surgical risk of the supported patients. However,
      the combination of improved patient management, multidisciplinary team work and
      standardization of ECLS protocols has recently yielded excellent results in
      several case series from high-volume transplant centres. Therein, it was
      demonstrated that, although the prevalence of complications remains higher in
      supported patients, there may be no difference in long-term graft function
      between supported and non-supported patients. These results are important,
      because most of the patients who require ECLS support in lung transplantation are
      young and have no other chance to survive, but to be transplanted. Moreover,
      there is no device for "bridging to destination" therapy in lung transplantation.
      Of note, the evidence in favour of ECLS support in lung transplantation was never
      validated by randomized controlled trials, but by everyday experience at the
      patient bed-side. Here, we review the state-of-the-art ECLS evidence for
      intraoperative and postoperative cardiopulmonary support in lung transplantation.

PMID- 30233891
TI  - Aortic allografts: final destination?-a summary of clinical tracheal substitutes.
AB  - The patient population in desperate need for an airway substitute are individuals
      with long segment tracheal defects that are considered, technically, inoperable.
      Regardless of the underlying etiology, benign or malignant growing processes,
      this patient category enters a palliative setting or require tracheal
      transplantation. Different airway substitutes have been categorized by Grillo as
      follows; tracheal transplantation, autogenous tissue, non-viable tissue, tissue
      engineering and foreign materials. These fields have been explored in the past in
      animal models and in clinical patients. Research on airway replacement has been
      exposed to a level of controversies in the past years. The field has been
      turbulent and apocryphal. In particular, the area of tissue-engineering using
      stem cells has suffered from a major set-back leaving scientists, clinicians and
      ethical committees skeptical. Recently, a hopeful study emerged using aortic
      allografts as tracheal substitutes in patients with airway defects. The initial
      results seem promising and reliable. The developments of the field at this point
      seem striking and hopeful. The focus of this review is to shed light on
      developments in the field of aortic allografts as substitute for tracheal
      replacement.

PMID- 30233892
TI  - Surgical embolectomy for acute massive pulmonary embolism: state of the art.
AB  - Massive pulmonary embolism (PE) is a severe condition that can potentially lead
      to death caused by right ventricular (RV) failure and the consequent cardiogenic
      shock. Despite the fact thrombolysis is often administrated to critical patients
      to increase pulmonary perfusion and to reduce RV afterload, surgical treatment
      represents another valid option in case of failure or contraindications to
      thrombolytic therapy. Correct risk stratification and multidisciplinary proactive
      teams are critical factors to dramatically decrease the mortality of this global
      health burden. In fact, the worldwide incidence of PE is 60-70 per 100,000, with
      a mortality ranging from 1% for small PE to 65% for massive PE. This review
      provides an overview of the diagnosis and management of this highly lethal
      pathology, with a focus on the surgical approaches at the state of the art.

PMID- 30233893
TI  - Percutaneous pleural drainage in patients taking clopidogrel: real danger or
      phantom fear?
AB  - Despite being categorized as a procedure associated with a low risk of iatrogenic
      hemorrhage, percutaneous pleural drainage in patients taking the ubiquitous
      antiplatelet agent clopidogrel is still commonly perceived as a risky
      proposition. There is mounting evidence, however, in support of the safety of
      percutaneous needle procedures in persons receiving this medication. Establishing
      that these pleural interventions can be performed safely without clopidogrel
      interruption would be of great clinical significance, especially in those taking
      it for recent cardiac stenting and therefore in danger of stent thrombosis should
      antiplatelet therapy (APT) be withheld. The purpose of the present review is to
      summarize the available data from published studies and series of thoracentesis
      and chest tube insertion in patients exposed to clopidogrel. Also incorporated
      into this review are relevant investigations from the thoracic surgery and
      interventional radiology experience, which contribute indirect evidence and help
      shape the context for interpreting the safety data reported in the pleural
      literature. At the end, an attempt is made to synthesize the current knowledge on
      this topic into conclusions for guiding practice.

PMID- 30233894
TI  - A strategy for measuring health outcomes and evaluating impacts of interventions
      on asthma and COPD-common chronic respiratory diseases in Global Alliance against
      Chronic Respiratory Diseases (GARD) countries.

PMID- 30233895
TI  - Lung adenocarcinoma patient progression with gastrointestinal metastasis response
      to subsequent tyrosine kinase inhibitors (TKIs) from re-biopsy of new occurring
      driver gene mutation.

PMID- 30233896
TI  - Pulmonary strongyloidiasis presenting micronodules on chest computed tomography.

PMID- 30233897
TI  - An atypical presentation of acute coronary syndrome.

PMID- 30233898
TI  - Bronchopleural phrenic fistula caused by methicillin-resistant staphylococcus
      aureus pneumonia.

PMID- 30233900
TI  - A rare case of pleomorphic adenoma with difficult diagnosis using biopsy.
AB  - An 85-year-old woman was found to have a nodule in the left S6 of the lung on
      computed tomography (CT); the pathological diagnosis from the CT-guided biopsy
      was adenoid cystic carcinoma. We accordingly performed left lower lobectomy.
      Pathologically, the biphasic cell population showed admixtures in varying
      proportions of epithelial and stromal elements, thereby indicating pleomorphic
      adenoma (PA). PA of the lung is extremely rare with reports of only 20 patients
      so far. Interestingly, this case was difficult to diagnose using CT-guided biopsy
      because the overview and biphasic cell population obtained on biopsy were
      garbled. Here we have reported our rare experience of PA.

PMID- 30233899
TI  - Case report of delayed radiotherapy-related pleural effusion following chest
      radiotherapy for lymphoma.

PMID- 30233901
TI  - Organizing pneumonia: a rare pulmonary manifestation of well-controlled
      ulcerative colitis.

PMID- 30233902
TI  - Chylothorax after thoracoscopic extended thymectomy: a case report and
      literatures review.

PMID- 30233903
TI  - Fatal hemothorax after thoracic epidural procedure for postoperative pain control
      in elderly esophageal cancer patient.

PMID- 30233904
TI  - Alan Daugherty: cardiovascular research takes courage to roll with the punches.

PMID- 30233905
TI  - Platelets-to-lymphocyte ratio and esophageal cancer.

PMID- 30233906
TI  - Inflammation in venovenous extracorporeal membrane oxygenation: villain or
      innocent bystander?

PMID- 30233907
TI  - Calpain and spectrin breakdown products in tuberculous pleural effusion.

PMID- 30233908
TI  - What we have known, what we do not know?-clonality of multifocal pulmonary ground
      glass opacities.

PMID- 30233909
TI  - Diagnostic implication of circulating microRNAs in acute aortic dissection.

PMID- 30233910
TI  - ESTS staging guidelines for non-small cell lung cancer: a good guide to best ever
      accuracy and high survival rate.

PMID- 30233911
TI  - Understanding effects of obstructive sleep apnoea and its treatment on the brain
      and autonomic regulation needs further research.

PMID- 30233912
TI  - Lung transplantation: chronic rejection and stem cell depletion.

PMID- 30233914
TI  - Erratum to multidisciplinary team approach on a case of bilateral tension
      pneumothorax.
AB  - [This corrects the article DOI: 10.21037/jtd.2018.04.81.].

PMID- 30233913
TI  - Risk stratification for severe acute respiratory distress syndrome requiring veno
      venous extracorporeal membrane oxygenation: a clinical need.

PMID- 30233915
TI  - Erratum to South African guideline for the management of community-acquired
      pneumonia in adults.
AB  - [This corrects the article DOI: 10.21037/jtd.2017.05.31.].

PMID- 30233916
TI  - Erratum to assessment of a respiratory face mask for capturing air pollutants and
      pathogens including human influenza and rhinoviruses.
AB  - [This corrects the article DOI: 10.21037/jtd.2018.03.103.].

PMID- 30233917
TI  - Family and Social Context Contributes to the Interplay of Economic Insecurity,
      Food Insecurity, and Health.
AB  - In this study, we show how household health, economic instability, and food
      insecurity are inextricably linked; disruptions in individual health or income
      create cumulative and interdependent challenges faced by multiple household
      members. Drawing upon semi-structured focus groups with English- and Spanish
      speaking clients of an urban food pantry, we demonstrate: (1) the impact of
      economic scarcity on health, (2) the impact of one household member's health on
      the health and food security of all household members, and (3) food sharing
      behaviors among family and social networks, including multi-generational families
      and non-kin individuals. We identify the gap between household-level assessments
      of food insecurity and individual-level health reports, which may obscure poor
      health among other household members. Understanding the social and family context
      of health and food insecurity may inform future interventions that address the
      interrelated challenges of diverse and disadvantaged households and communities.

PMID- 30233918
TI  - Lumbar Epidural Steroid Injections.
AB  - Lumbar radiculopathy is a common diagnosis for patients who present with low-back
      pain and leg pain, typically along a particular dermatome. This pain is commonly
      associated with a lumbar disc herniation. The prognosis is usually favorable, and
      the symptoms can resolve spontaneously over time. In patients in whom leg and
      back symptoms are severe, lumbar epidural (cortico)steroid injections are good
      options for the short to medium-term management of pain. Currently, lumbar
      epidural steroid injections are performed with radiographic guidance systems and
      fluoroscopy. This method is preferred because of the increased accuracy in needle
      placement and the reduced risk of injury to nerves and vascular structures. The
      procedure is performed with the following steps: (1) Following appropriate
      patient selection through clinical evaluation and assessment of imaging studies
      such as computed tomography or magnetic resonance imaging, the patient is
      prepared and draped after providing written informed consent. (2) The level of
      neural compression to be injected is identified with intermittent fluoroscopy and
      the use of a radiopaque marker. (3) The skin and subcutaneous tissues are
      anesthetized. (4) A spinal needle (Quincke or Tuohy type) is inserted after
      tissues are fully anesthetized. The needle is slowly advanced with the use of
      intermittent fluoroscopy until the target is reached. In the case of an
      interlaminar approach, this would be associated with a loss of syringe resistance
      and piercing of the ligamentum flavum. In the case of a transforaminal approach,
      this would be associated with the 6 o'clock position of the pedicle on the side
      in question. (5) Contrast material is then injected with the use of live
      fluoroscopy to confirm appropriate placement and exclude intravascular and
      intrathecal injection. (6) When adequate placement is confirmed, a solution of
      steroid and anesthetic is administered. The needle is then removed. Most outcome
      reports after lumbar epidural steroid injections are favorable for radicular
      symptoms. Associated back pain may typically improve as well. Common
      complications include injection site pain or soreness, infections, allergy, and
      inadvertent dural puncture with spinal headache.

PMID- 30233920
TI  - Tibiotalar Arthrodesis Conversion to Total Ankle Arthroplasty.
AB  - Introduction: Although conversion of the painful ankle arthrodesis to total ankle
      arthroplasty remains controversial, this surgical modality has satisfactorily
      expanded the treatment armamentarium for addressing this pathology. Indications &
      Contraindications:  Step 1 Preoperative Preparation and Surgical Planning:
      Preoperative preparation and planning is similar to that for a primary total
      ankle arthroplasty, and implants designed for primary arthroplasty can be used in
      most patients managed with conversion to total ankle replacement. Step 2 Patient
      Positioning: Position the patient as for a primary total ankle replacement. Step
      3 Remove Hardware and Insert Prophylactic Malleolar Screws: Preserve
      exsanguination time by removing hardware prior to inflating the tourniquet. Step
      4 Recreate the Tibiotalar Joint: Recreate the native joint line, which can be
      relatively easy in selected patients and challenging in others. Step 5 Set the
      Optimal Talar Slope: Set the optimal talar slope, which can be challenging,
      particularly when the ankle arthrodesis is malunited in equinus. Step 6 Recreate
      the Medial and Lateral Gutters: Because the former medial and lateral
      articulations between the talus and the malleoli can be difficult to define, use
      careful surgical technique to avoid compromise of the malleoli and excessive
      talar resection. Step 7 Mobilize the Ankle and Use Bone Graft in Defects from
      Previous Hardware: To avoid potential malleolar fractures, mobilize the ankle
      only after the prophylactic malleolar screws have been placed; the tibial and
      talar cuts, completed; the gutters, reestablished; all resected bone, removed;
      and scar tissue from the posterior aspect of the ankle, excised; thereafter,
      conversion total ankle arthroplasty is similar to a primary total ankle
      replacement, with the exception of potential bone defects where prior hardware
      was positioned. Step 8 Talar Preparation: Perform the routine steps for primary
      total ankle arthroplasty, often ignoring bone defects from the ankle arthrodesis
      hardware, but plan to repair the defects with bone-grafting before implanting the
      final talar component. Step 9 Tibial Preparation and Definitive Components:
      Perform tibial preparation in a manner similar to that used for primary total
      ankle arthroplasty. Results: We performed 23 conversion total ankle
      arthroplasties in patients who had an ankle arthrodesis, including those with
      pain despite successful fusion and those with painful nonunions9. Pitfalls &
      Challenges: 

PMID- 30233919
TI  - Arthroscopic Osseous Bankart Repair in the Treatment of Recurrent Anterior
      Glenohumeral Instability.
AB  - Introduction: Anterior glenohumeral instability associated with an anterior
      inferior fracture of the glenoid (osseous Bankart lesion) can be treated
      successfully with arthroscopic, rather than open, surgical repair, or fixation of
      the osseous fragment. Indications & Contraindications:  Step 1 Patient
      Positioning: Place the patient in the beach-chair position and examine both
      shoulders for laxity after induction of general anesthesia with an interscalene
      block. Step 2 Portal Placement: Create a standard posterior viewing portal and
      anterior and anterosuperior working portals. Step 3 Mobilization: Separate the
      displaced osseous fragment associated with the labroligamentous complex from the
      glenoid neck and mobilize the labroligamentous complex together with the fragment
      up to the 7 o'clock or 7:30 position (in a right shoulder). Step 4 Inferior
      Labrum Repair: Perform an inferior labrum repair by inserting 2 suture anchors at
      the anteroinferior part of the glenoid face. Step 5 Osseous Fragment Fixation:
      Fix the osseous fragment by passing the sutures either through or around the
      fragment with use of a bone penetrator, or Bone Stitcher, while stabilizing the
      labrum and fragment with a large grasper. Step 6 Augmentation Procedures: Rotator
      interval closure, done with the arm in >60 degrees  of external rotation, is the
      most frequently performed augmentation procedure. Results: A consecutive series
      of 46 patients with an osseous Bankart lesion who demonstrated >15% glenoid bone
      loss underwent osseous Bankart repair, which was performed regardless of the
      fragment size, between January 2005 and December 20061. Pitfalls & Challenges: 

PMID- 30233921
TI  - Treatment of Clubfoot Using the Ponseti Method.
AB  - The Ponseti method consists of a specific technique of manipulation of the
      clubfoot deformity, followed by the application of a plaster cast with the foot
      in the corrected position. A percutaneous tenotomy of the Achilles tendon is done
      prior to the final cast to gain complete correction in most patients. Bracing
      with a foot abduction orthosis is necessary to minimize relapse of the deformity.
      The method begins with the Ponseti manipulation and consists of the following
      steps: (1) Identify the head of the talus by palpation. (2) Supinate the forefoot
      to eliminate the cavus deformity and create a normal-appearing arch. (3) Abduct
      the forefoot with the vector of force parallel to the sole of the foot while
      using the lateral head of the talus as the fulcrum and maintaining the reduction
      of the cavus deformity. (4) This manipulation is followed by the application of
      an above-the-knee cast with the foot in the corrected position. (5) The
      manipulation and casting steps are repeated every 5 to 7 days until the foot is
      abducted approximately 50 degrees  from the frontal plane of the tibia. (6) In
      most patients (60% to >90%), a percutaneous tenotomy of the Achilles tendon is
      necessary to correct the residual ankle equinus after gaining full abduction of
      the foot with the manipulations. (7) The final cast is applied and worn for three
      weeks. (8) After removal of the final cast, the patient is managed with bracing
      with a foot abduction orthosis for 23 hours per day for 3 months. Bracing at
      night and during nap time is recommended until the child is 4 to 5 years old. The
      cavus deformity is eliminated after the application of 2 or 3 casts by the simple
      positioning maneuver. Abduction of the forefoot in the plane of the sole of the
      foot while using the head of the talus as the fulcrum results in the correction
      of the midfoot adduction deformity simultaneously with the hindfoot varus and the
      subtalar component of the equinus deformity. After full abduction is obtained,
      the cavus, adduction, and subtalar varus and equinus deformities are all
      completely corrected. The only residual deformity is the ankle equinus. Most feet
      require a percutaneous tenotomy to fully correct the ankle component of the
      equinus. The tenotomy can be performed as an outpatient procedure under local
      anesthetic without the need for sedation. If the foot can be dorsiflexed to >15
      degrees  (without midfoot breach), a tenotomy is unnecessary. This manipulation
      allows complete correction of almost all idiopathic clubfeet in 4 to 7 sessions.
      Long-term follow-up (mean, 34 years; range, 25 to 42 years) has shown that
      clubfeet treated with the Ponseti method function as well as normal feet with
      respect to pain and level of activity.

PMID- 30233922
TI  - Primary Triple Arthrodesis for Management of Rigid Flatfoot Deformity.
AB  - Introduction: Primary triple arthrodesis is a powerful and reliable procedure for
      stabilizing and correcting painful rigid flatfoot deformities with a low rate of
      complications. Indications & Contraindications:  Step 1 Preoperative Planning:
      Pay careful attention to the history, physical examination, and weight-bearing
      radiographic studies as they are critical for selecting patients who will benefit
      from a triple arthrodesis. Step 2 Room Setup and Patient Positioning: Position
      the patient supine on the operating table with the toes pointing straight up to
      the ceiling. Step 3 Incisions and Exposure: For a standard triple arthrodesis,
      use 2 incisions: a lateral sinus tarsi incision, which allows exposure of the
      subtalar joint, CC joint, and lateral aspect of the TN joint, and a medial
      incision, which provides exposure of the TN joint. Step 4 Joint Preparation:
      Ensure that joint preparation is thorough as this is critical for the success of
      any hindfoot arthrodesis. Step 5 Reduction of Deformity: Reduce the TN joint
      first, followed by the subtalar joint, restoring a plantigrade foot and
      approximately 5 degrees  of hindfoot valgus alignment. Step 6 Joint Fixation:
      Perform rigid fixation of the subtalar joint first, followed by fixation of the
      TN and CC joints. Step 7 Accessory Procedures: Accessory procedures are often
      required in addition to the triple arthrodesis to ensure that appropriate
      hindfoot alignment and a plantigrade foot are achieved. Step 8 Wound Closure:
      Perform a staged wound closure, taking care to maximize soft-tissue coverage over
      the involved hindfoot joints. Step 9 Postoperative Care: Ensure that the patient
      follows strict non-weight-bearing precautions in the immediate postoperative
      period to limit micromotion at the arthrodesis sites and allow for timely fusion.
      Results: In one of the largest published series of patients managed with triple
      arthrodesis (111 patients), Pell et al. reported a union rate of 98% at a minimum
      follow-up of 2 years, with 91% of patients indicating that they would be willing
      to repeat the procedure under similar circumstances4. Pitfalls & Challenges: 

PMID- 30233923
TI  - Reconstructing Pelvic Discontinuity and Severe Acetabular Bone Loss in Revision
      Hip Arthroplasty with a Massive Allograft and Cage.
AB  - Introduction: The use of a massive allograft along with an antiprotrusio cage for
      the treatment of large periprosthetic acetabular defects can restore structural
      integrity to the pelvis and provide durable revision-free survival. Indications &
      Contraindications:  Step 1 Expose the Acetabulum Video 1 and Figs 1-A and 1-B:
      Perform an extensile approach to the acetabulum. Step 2 Remove the Existing
      Acetabular Component Video 1 and Figs 2-A and 2-B: Ensure that the appropriate
      tools are available for removal of the existing acetabular component. Step 3
      Prepare the Acetabulum Fig 3: It is important to remove fibrous tissue around the
      acetabulum to get to healthy bleeding bone. Step 4 Prepare the Bulk Allograft
      Video 2 and Figs 4-A 4-B and 4-C: It is important to remove all of the native
      cartilage from the graft to allow for osseous ingrowth potential. Step 5 Place
      the Bulk Allograft into the Acetabular Defect and Fill Excess Space with
      Allograft Chips: Ensure that the graft properly fits within the acetabular
      defect. Step 6 Secure the Graft to the Acetabulum and Ream the Allograft: It is
      important to stabilize the bulk allograft to the pelvis before reaming. Step 7
      Implant the Cage Video 4 and Figs 9-A 9-B and 9-C: Impact the cage implant into
      position and secure it to the pelvis with as many screws as necessary to obtain a
      secure implant. Step 8 Cement the Polyethylene Cup and Perform Trial Reduction of
      the Hip: Cement the polyethylene cup in the proper orientation and reduce the
      hip. Results: We reviewed 72 cage constructs in 68 patients at a mean follow-up
      of 5.1 years (range, 1.2 to 10.7 years)3. Pitfalls & Challenges: 

PMID- 30233924
TI  - Treatment of Distal Radial Fractures by Open Reduction and Internal Fixation with
      a Volar Locking Plate.
AB  - The volar locking plate is a popular implant for surgical management of unstable
      distal radial fractures. We routinely utilize this system for all distal radial
      fractures except for those with entrapped intra-articular fragments and fractures
      with a displaced dorsomedial facet fracture (which is hard to capture with the
      volar approach alone). In this video, we describe in detail the necessary steps
      for successful placement of the volar locking plate, starting with preoperative
      planning and ending with expected outcomes. The approach that we utilize is
      through the flexor carpi radialis tendon sheath and avoids the radial artery. In
      the video, we describe 4 variations on the application of a volar locking plate:
      (1) the standard technique after appropriate reduction and provisional fixation
      with Kirschner wires, (2) regaining length through a shortened distal radial
      fracture, (3) using the volar plate to assist in the reduction and regain volar
      tilt, and (4) intraoperative management of coronal shift of the distal fragment.
      Complications reported for the volar locking plate have decreased with newer low
      profile plate designs; however, they still include volar tendon irritation and/or
      rupture and median neuropathy. Postoperatively, we advise a brief 2-week period
      of immobilization for wound-healing, which is followed by a period during which a
      removable wrist splint is used and patients are instructed on the performance of
      a hand therapy regimen.

PMID- 30233926
TI  - Surgical Technique for Arthroscopic Lateral Collateral Ligament Repair.
AB  - Introduction: Arthroscopic repair of the lateral collateral ligament (LCL)
      complex in patients who have posterolateral rotatory instability after an
      unstable elbow dislocation, with or without an intra-articular fracture, is an
      alternative treatment for restoring stability of the elbow and obtaining
      successful clinical and radiographic results. Indications & Contraindications: 
      Step 1 Computed Tomography CT Magnetic Resonance Imaging MRI and Preoperative
      Planning: Obtain radiographs and CT and MRI scans to make an accurate analysis of
      the fracture patterns and develop an understanding of soft-tissue comorbidities.
      Step 2 Position the Patient and Place the Portals: Place the patient in the
      lateral decubitus position and create proximal anteromedial, proximal
      anterolateral, anterolateral, and radial head portals as working portals and a
      posterior soft-spot portal as a viewing portal for the repair of the LCL complex.
      Step 3 Diagnostic Arthroscopy: Identify concomitant radial head and coronoid
      fractures, and confirm the LCL-complex tear intraoperatively. Step 4 Management
      of Concomitant Injuries: Treat intra-articular fractures arthroscopically before
      the LCL-complex repair. Step 5 Arthroscopic LCL-Complex Repair Video 1: After
      soft-tissue debridement using the soft-spot portal as a viewing portal and the
      proximal anterolateral portal as a working portal, decorticate the footprint of
      the humeral attachment of the LCL complex with use of a shaver or burr and then
      make a modified Mason-Allen stitch using a needle, fixing the suture with a
      knotless anchor, to achieve a stable elbow joint. Step 6 Postoperative
      Management: After postoperative immobilization of the elbow for 2 to 3 days,
      instruct the patient to perform passive exercises, returning to a full range of
      motion at 4 to 6 weeks after surgery, and typically returning to full activity at
      3 months after the operation. Results: To date, arthroscopic LCL-complex repair
      has produced excellent results, with all 13 patients in our original study
      reporting complete resolution of the elbow instability and demonstrating a
      negative result on the lateral pivot-shift test15. Pitfalls & Challenges: 

PMID- 30233925
TI  - Tibial Tubercle Osteotomy to Aid Exposure for Revision Total Knee Arthroplasty.
AB  - Introduction: A tibial tubercle osteotomy can provide reliable and safe exposure
      during revision total knee arthroplasty with a high union rate, low complication
      rate, and predictable outcomes. Indications & Contraindications:  Step 1
      Preoperative Planning Figs 1-A through 2-B: Determine the need for an extensile
      approach on the basis of the preoperative knee range of motion; position of the
      patella; bone quality; medical comorbidities; and cement mantle, tibial keel or
      stem, and thickness of the anterior tibial cortex. Step 2 Incision and
      Arthrotomy: Create full-thickness subcutaneous flaps and perform a medial
      parapatellar arthrotomy with complete synovectomy and careful excision of scar
      tissue from the medial and lateral gutters. Step 3 Incision Extension and
      Preparation for Tibial Tubercle Osteotomy Figs 3 and 4 Videos 1 2 and 3: Extend
      the skin and subcutaneous dissection distal to the tibial tubercle and mark the
      chevron osteotomy using electrocautery. Step 4 Tibial Tubercle Osteotomy Fig 5
      Videos 4 and 5: Perform the osseous cut for the tibial tubercle osteotomy with a
      thin saw blade in a medial-to-lateral direction, such that the fragment hinges on
      the lateral soft tissue and musculature. Step 5 Revision Total Knee Arthroplasty
      Videos 6 and 7: With the knee maximally flexed and lateral subluxation of the
      extensor mechanism, for full visualization of the femoral and tibial components,
      remove the components and perform the knee revision. Step 6 Preparation for
      Insertion of Tibial Component: The final tibial component should have a
      diaphyseal stem long enough to bypass the distal extent of the tibial tubercle
      osteotomy by at least 2 cortical diameters. Step 7 Trialing and Insertion of
      Final Tibial Component Figs 6 and 7 Videos 8 9 and 10: When cementing the final
      tibial component, take care to remove cement anterior to the tibial stem that
      would otherwise impede complete reduction of the osteotomy fragment and interfere
      with osseous union at the osteotomy site. Step 8 Reduction of Tibial Tubercle
      Osteotomy Fragment Figs 8 and 9 Videos 11 12 and 13: Manually position the
      osteotomized bone fragment over the tibia and obtain an anatomic reduction either
      freehand or using bone clamps, depending on the soft-tissue tension. Step 9
      Fixation of Tibial Tubercle Osteotomy Fragment Video 14: Obtain rigid fixation
      with a 6.5-mm screw proximally and 2 sets of doubled-over 18-gauge wires
      distally. Step 10 Stressing the Osteotomy Site and Wound Closure Figs 10 11 and
      12 Videos 15 and 16: Stress the osteotomy site by flexing the knee 90 degrees ,
      deflate the tourniquet, place a drain if needed, and close. Step 11 Postoperative
      Restrictions and Protocol Figs 13-A and 13-B: Allow weight-bearing as tolerated
      and a 0 degrees  to 90 degrees  range of motion in a hinged knee brace. Results:
      Tibial tubercle osteotomy to aid in exposure during revision total knee
      arthroplasty has been reported to yield favorable outcomes in the orthopaedic
      literature7-18. Pitfalls & Challenges: 

PMID- 30233927
TI  - Extensile Lateral Approach for the Operative Management of a Displaced Intra
      Articular Calcaneus Fracture.
AB  - Calcaneal fractures account for approximately 1.2% of all fractures and 60% of
      all tarsal bone fractures. Almost 75% present as displaced, intra-articular
      fractures. Because of the complex articular and osseous anatomy, the vulnerable
      soft-tissue envelope, and the technically challenging approach needed for
      fixation, these fractures are often treated nonoperatively, resulting in poor
      outcomes. These poor outcomes can include entrapment of the posterior tibial and
      sural nerves, impingement, dislocation or entrapment of peroneal tendons, a
      widened heel with a loss of height, hindfoot varus or valgus, formation of
      painful exostoses, development of posttraumatic arthritis of the subtalar and
      calcaneocuboid joints, and impingement of the ankle joint. The current scientific
      literature supports fixation of displaced, intra-articular fractures. The
      principles of surgical fixation consist of reconstructing the height (obtained by
      improving the Bohler angle), narrowing the width, reconstructing the length,
      correcting any varus deformity of the tuberosity, and anatomically reducing the
      joint. However, at the time of initial presentation, there is often substantial
      swelling, with or without fracture blisters, that needs to be resolved prior to
      surgical fixation. During this waiting period, radiographic and computed
      tomography (CT) evaluations should be performed to assess the fracture pattern.
      Once re-epithelialization of the blisters and wrinkling of the skin are noted,
      open reduction and internal fixation (ORIF) can be performed. The steps to an
      ORIF consist of (1) the use of an extensile lateral incision, with a
      subperiosteal dissection, that develops a full-thickness fasciocutaneous flap;
      (2) removal of the lateral wall, to allow visualization of the impacted joint;
      (3) removal of the lateral third or half of the joint to allow visualization of
      the medial two-thirds or half of the joint; (4) disimpaction of the medial half
      of the joint to its normal height, along with medialization of the tuberosity;
      (5) anatomic reduction of the posterior facet and fixation with lag screw(s); (6)
      possible use of a bone graft and replacement of the lateral wall; (7) spanning
      the calcaneus with a plate and screws; and (8) closure of the fasciocutaneous
      flap and skin over a drain.

PMID- 30233928
TI  - Glenoid Bone-Grafting in Revision to a Reverse Total Shoulder Arthroplasty:
      Surgical Technique.
AB  - Introduction: Reverse shoulder arthroplasty has emerged as a very good treatment
      option for patients in salvage situations, such as the revision setting with
      glenoid bone loss. Indications & Contraindications:  Step 1 Preoperative
      Evaluation and Planning: For patients undergoing revision shoulder arthroplasty,
      perform the preoperative evaluation with radiographs, computed tomography (CT),
      and digital templating software as they play a key role (Video 1). Step 2
      Surgical Approach and Humeral Component Management: Perform all operations with
      the patient in the beach-chair position. Step 3 Glenoid Component Removal and
      Preparation: Glenoid exposure is the key to the operation. Step 4 Assessment of
      Glenoid Bone Stock and Bone-Grafting Algorithm: Use bone graft if the glenoid is
      thought to be inadequate for stable fixation in an acceptable position. Step 5-A
      Manage a Peripheral Defect with >=50% Implant-Bone Contact with a Structural
      Allograft or Humeral Autograft: When a peripheral defect contributes to either
      glenoid anteversion (anterior) or retroversion (posterior), but the implant has
      >=50% contact with the native bone, consider using a structural autograft from
      the local humerus (preferred), if available, or a structural allograft (Video 1).
      Step 5-B Manage a Peripheral Defect with <50% Implant-Bone Contact with a
      Structural Autograft from the Iliac Crest or Proximal Part of the Humerus: In
      shoulders with a peripheral defect with <50% contact with the native glenoid and
      substantial alterations in glenoid version, consider using a structural autograft
      from the proximal part of the humerus (preferred), if available, or the iliac
      crest (Figs. 2-A, 2-B, 2-C, and 3; Video 1). Step 5-C Manage a Central Defect
      with >=30% Implant-Bone Contact with Morselized Bone-Grafting Allograft or
      Autograft: In shoulders with a central defect with >=30% contact between the
      baseplate and the native glenoid, with adequate primary stability of the central
      screw and/or peg, use morselized local autograft (preferred), if available, or
      corticocancellous allograft, to restore the lateral offset of the native glenoid
      and implant-bone contact area. Step 5-D Manage a Central Global Defect with <30%
      Implant-Bone Contact with a Structural Autograft from the Iliac Crest or Proximal
      Part of the Humerus: As a large central or global deficiency can lead to
      excessive glenoid medialization (Figs. 4-A, 4-B, and 4-C), use a structural
      tricortical autograft from the iliac crest to restore glenoid structure and
      support implantation, as well as increase the offset of the glenoid component,
      enhancing stability and potentially reducing the risk of scapular notching8. Step
      5-E Manage a Superior Defect with <50% Implant-Bone Contact and Loss of Tilt with
      a Structural Autograft from the Iliac Crest or Proximal Part of the Humerus: For
      a superior deficiency with <50% contact between the implant and the native bone
      and a loss of neutral tilt, avoid superior tilt as it is critical to obtain
      either neutral or inferior tilt of the glenoid (keep this in mind when placing
      the central cannulated Kirschner wire for drilling the central screw) and use
      structural autograft for larger defects to prevent superior tilt, with the source
      of the graft preferentially from the humeral neck resection; however, if there is
      not adequate proximal humeral bone, a tricortical graft from the ipsilateral
      iliac crest can be used. Step 6 Placement of Baseplate Screws and Glenosphere and
      Implantation of the Humeral Component:  Step 7 Postoperative Care:  Results: In
      our practice, glenoid bone-grafting was performed in 29% of the 143 shoulders
      revised using reverse components2. Pitfalls & Challenges: 

PMID- 30233929
TI  - Closed Distraction and Gradual Deformity Correction of Stiff Hypertrophic Tibial
      Nonunions with Hexapod External Fixation.
AB  - Introduction: Closed distraction of stiff tibial nonunions with a hexapod
      external fixator can predictably lead to union without the need for additional
      surgery or bone graft. Indications & Contraindications:  Step 1 Fibular
      Osteotomy: Resect 5 to 10 mm of the fibula, from its distal half or at the level
      of the fibular deformity if present. Step 2 Application of Hexapod Proximal Ring
      Using 'Rings First' Method: Apply the proximal ring orthogonal to the proximal
      bone segment. Step 3 Application of Hexapod Distal Ring Using 'Rings First'
      Method: Apply the distal ring orthogonal to the distal bone segment. Step 4
      Connection of Struts and Application of Sterile Dressing: Connect the proximal
      and distal rings with 6 oblique struts. Step 5 Postoperative Planning Deformity
      Correction and Distraction: Perform gradual deformity correction and distraction
      at a rate of 1 mm per day. Step 6 Postoperative Care Until Union: Perform pin
      site care and functional rehabilitation. Step 7 'Trial of Union' and Frame
      Removal: Ensure adequate union prior to removal of the circular fixator. Results:
      Hexapod closed distraction has been successfully used for the management of stiff
      hypertrophic tibial nonunions in our practice over the last 6 years. Pitfalls &
      Challenges: 

PMID- 30233930
TI  - Anterior Cervical Discectomy and Fusion.
AB  - Anterior cervical discectomy and fusion can be performed for a variety of
      pathologies but is most commonly used for the treatment of cervical radiculopathy
      or myelopathy. The procedure involves an anterior decompression of the disc space
      followed by interbody grafting and fusion. Supplemental anterior plating is
      commonly performed, and in certain circumstances, posterior instrumentation may
      provide additional fixation. The procedure includes the following steps: (1) The
      use of an anterior approach to the cervical spine, most commonly the Smith
      Robinson approach medial to the sternocleidomastoid muscle and the carotid
      sheath. (2) Confirmation of the proper spinal level. (3) Elevation of the longus
      colli muscle, which acts as a cuff for the placement of retractors. (4) Removal
      of the involved disc and decompression of the spinal cord and nerve roots. This
      is facilitated by disc space distraction, most commonly via distraction pins.
      Osteophytes along the floor of the spinal canal impinging on the spinal cord are
      removed with a burr. Soft disc and anular material are also removed, usually with
      curets and rongeurs. Uncovertebral osteophyte resection and foraminotomies are
      completed to decompress the exiting nerve roots. (5) Carpentry and decortication
      of the end plates in preparation for fusion. (6) Sizing of the disc space
      followed by insertion of an interbody graft. (7) Anterior fixation, most commonly
      via application of a plate-and-screw construct. (8) Hemostasis and closure.

PMID- 30233931
TI  - Arthroscopic Removal of Rotator Cuff Calcifications: Operative Technique.
AB  - Introduction: In this article, we present our operative technique for the removal
      of rotator cuff calcifications. Indications & Contraindications:  Step 1 Setup
      and Patient Positioning: Perform the shoulder arthroscopy with the patient in the
      beach-chair position with a shoulder positioner. Step 2 Glenohumeral Inspection:
      Perform an arthroscopic inspection of the glenohumeral joint to exclude
      concomitant lesions. Step 3 Subacromial Inspection and Identification of
      Subacromial Landmarks: Ensure that subacromial placement of the arthroscope and
      identification of the subacromial landmarks are correct as they are necessary for
      localization of the rotator cuff calcification. Step 4 Identification and Removal
      of Rotator Cuff Calcification: With a spinal needle, localize and needle the
      rotator cuff calcification. Results: In our series, all patients undergoing
      arthroscopic calcification removal exhibited significant improvement in the
      Constant score (p = 0.003), Quick DASH (an abbreviated version of the
      Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire) (p < 0.001), and
      Simple Shoulder Test (p < 0.001) at 1 year after the operation8. Pitfalls &
      Challenges: 

PMID- 30233932
TI  - Arthroscopic Glenoid Reconstruction for Chronic Anteroinferior Shoulder
      Instability Using a Tricortical Iliac Crest Bone Graft.
AB  - Introduction: Arthroscopic glenoid reconstruction using a tricortical iliac crest
      bone graft is performed to anatomically reconstruct the glenoid and reestablish
      glenohumeral stability in patients with chronic anteroinferior shoulder
      instability and substantial osseous defects1-3. Indications & Contraindications: 
      Step 1 Patient Positioning: Place the patient in the lateral decubitus position
      and prepare the arm and ipsilateral iliac crest. Step 2 Diagnostic Arthroscopy
      and Portal Placement: Perform a diagnostic arthroscopy via the posterior portal
      and establish an anteroinferior, an anterosuperior, and a deep anteroinferior
      portal. Step 3 Capsulolabral Complex Release and Scapular Neck Preparation:
      Depending on the pathology and morphology of the defect, release the
      capsulolabral complex from the scapular neck and prepare the glenoid rim and
      scapular neck with a motorized burr to ensure adequate osseous healing. Step 4
      Harvesting and Preparation of the Iliac Crest Bone Block: Harvest an autologous
      tricortical iliac crest bone block from the ipsilateral side and contour it
      appropriately for an anatomic reconstruction of the glenoid. Step 5 Graft
      Insertion and Positioning: Enlarge the passage for the graft through the rotator
      interval, insert the bone block, and position it anatomically at the scapular
      neck. Step 6 Graft Fixation: With the aid of a drill sleeve, temporarily
      stabilize the graft using Kirschner wires and then definitively attach it to the
      scapular neck using 2 Bio-Compression screws. Step 7 Capsulolabral Repair:
      Reattach the capsulolabral complex to the original glenoid, inferior and superior
      to the bone block, using 2 knotless suture anchors to complete the anatomic
      reconstruction of the glenoid. Step 8 Rehabilitation and Postoperative Treatment:
      Immobilize the arm for 6 weeks postoperatively and limit flexion and external
      rotation during this time period. Results: Fifteen patients with a mean age of
      31.4 years (range, 17 to 49 years) with anteroinferior glenohumeral instability
      and substantial glenoid defects underwent arthroscopic iliac crest bone-grafting
      and were prospectively evaluated for an average period of 20.6 months (range, 12
      to 65 months)12. Pitfalls & Challenges: 

PMID- 30233933
TI  - Lateral Clavicle Fracture Fixation Using a Superiorly Placed Locking Plate.
AB  - Clavicle fractures are common injuries that account for 4% of all fractures, and
      approximately 21% of clavicle fractures are lateral. Studies have demonstrated
      that displaced lateral clavicle fractures with disruption of the coracoclavicular
      ligaments have nonunion rates as high as 28%. Many surgical techniques for
      fixation of lateral-end clavicle fractures have been proposed. More recently,
      locking plate technology has led to the development of superiorly placed locking
      plates, which are used when the distal fragment is large enough and which offer
      greater biomechanical stability in osteoporotic or metaphyseal bone. Our surgical
      technique for use of a compression plate for an unstable and displaced lateral
      clavicle fracture consists of the following steps. Step 1: identification of the
      fracture pattern and surgical planning. Step 2: setup of the operating room with
      the image intensifier in an optimum position for satisfactory intraoperative
      images. Step 3: approach, through a bra-strap incision centered over the
      fracture. Step 4: reduction of the fracture and temporary stabilization. Step 5:
      implant selection based on sizing and patient anatomy. Step 6: application of the
      plate of choice and fixation with a combination of proximal bicortical screws and
      distal locking screws. Step 7: closure in layers and application of postoperative
      slings and dressings. Patients follow a graduated physiotherapy regimen
      postoperatively. Studies have demonstrated high union rates following lateral
      clavicle fracture fixation with good-to-excellent functional outcomes and a
      combined complication rate of approximately 6%.

PMID- 30233934
TI  - Minimally Invasive Decompression in Lumbar Spinal Stenosis.
AB  - Introduction: Unlike traditional open laminectomy, minimally invasive
      decompression (MID) spares the important midline structures of the spine (i.e.,
      the spinous process and the supraspinous and interspinous ligaments). Indications
      & Contraindications:  Step 1 Preoperative Planning: Determine the levels and
      laterality for the decompression on the basis of the symptoms and findings on the
      MRI scan. Step 2 Operating Room Setup: Ensure the correct positioning of the
      patient and the proper setup of the equipment. Step 3 Marking the Levels: Use
      fluoroscopy to localize the level(s) of the stenosis. Step 4 Skin Incision and
      Tube Positioning: Ensure the correct placement of the tube. Step 5 Resection of
      the Lower Part of the Lamina: Use a high-speed drill and Kerrison rongeur to
      enter the spinal canal. Step 6 Resection of the Medial Part of the Facet Joint:
      Proceed cautiously at the point where the spinal canal is usually narrowest. Step
      7 Resection of the Ligamentum Flavum: Resect the ligamentum flavum piecemeal with
      a Kerrison rongeur. Step 8 Crossover Technique Optional: Use the crossover
      technique to reach across the midline and decompress the contralateral lateral
      recess (Video 3). Step 9 Closing the Wound: Perform a check to be certain that
      all steps have been completed before closing the skin. Results: In the study by
      Lonne et al., the 41 patients managed with MID had significant improvement at 6
      weeks and throughout the 2-year observation period7. Pitfalls & Challenges: 

PMID- 30233935
TI  - Patient-Matched Implementation for Reverse Total Shoulder Arthroplasty.
AB  - Introduction: Three-dimensional (3D) preoperative planning and patient-specific
      instrumentation (PSI) improve accuracy of glenoid component implantation in
      reverse shoulder arthroplasty. Indications & Contraindications:  Step 1
      Preoperative Virtual 3D Planning Video 1: Use a 3D software tool for virtual
      preoperative planning of glenoid component implantation. Step 2 Patient
      Positioning and Surgical Approach Video 2: Place the patient in a semi-beach
      chair position and perform a standard deltopectoral approach. Step 3 Humeral
      Preparation Video 3: Prepare the humeral side for implantation of the humeral
      component using standard instrumentation. Step 4 Glenoid Exposure and Preparation
      Video 4: Expose the glenoid and prepare the glenoid surface for component
      implantation. Step 5 Glenoid Preparation and Implantation of the Glenoid
      Baseplate Using 4 PSI Guides Video 5: Use the 4 PSI guides to prepare the glenoid
      for component implantation according to the preoperative plan. Step 6 Definitive
      Implantation of the Components and Reduction Video 6: Implant the glenosphere and
      humeral component and reduce the prosthesis. Step 7 Postoperative Rehabilitation
      Protocol: Start passive and active-assisted exercises immediately, and begin
      muscle strengthening and active exercises at 6 weeks. Results: A recent
      prospective, comparative study assessed the influence of 3D preoperative planning
      and PSI guidance of glenoid component positioning in total shoulder arthroplasty
      and reverse shoulder arthroplasty18. Pitfalls & Challenges: 

PMID- 30233936
TI  - Submuscular Plate for Pediatric Femoral Fractures.
AB  - Management of pediatric femoral fractures is dependent on patient age and injury
      pattern. For length-stable femoral shaft fractures in school-age children (5 to
      11 years of age), flexible intramedullary nailing (IMN) is a popular treatment
      method. However, for fracture patterns that are length-unstable or involve the
      proximal or distal third of the femur, flexible IMN has a higher rate of
      postoperative complications. Use of a submuscular bridge plate has been shown to
      be an effective alternative to IMN for these injuries. Because this long plate is
      inserted with a minimally invasive technique and indirect reduction, it acts as
      an internal type of "external fixator," thereby avoiding soft-tissue stripping at
      the fracture site and decreasing strain across the fracture site.Step 1: Position
      the patient supine on a radiolucent table with a bump under the ipsilateral
      hip.Step 2: Lay a 4.5-mm narrow stainless-steel plate over the injured thigh and
      use fluoroscopy to determine the appropriate length for this plate. Contour the
      plate as needed.Step 3: Make a lateral, longitudinal incision of 2 to 3 cm at the
      proximal or distal part of the femur through the iliotibial band. Elevate the
      vastus lateralis extraperiosteally from the femur using a Cobb elevator. Pass the
      plate through this plane proximally or distally while maintaining contact between
      the plate and the femur.Step 4: Adjust the plate position using fluoroscopy.
      Obtain fracture reduction using closed techniques and secure the plate
      temporarily with Kirschner wires through the most proximal and distal holes.Step
      5: Place the first screw near the end of the plate under direct visualization.
      Place the second screw using a percutaneous technique and insert it immediately
      proximal or distal to the fracture site where the femur is farthest from the
      plate. The drilling and length measurement of this screw are fluoroscopically
      aided and will bring the plate down into contact with the femoral cortex.Step 6:
      Place the remaining screws in a similar fashion; 3 screws proximal and distal to
      the fracture site provide adequate stability. Locking screws or lag screws are
      typically not necessary in this construct. Obtain final radiographs to ensure
      appropriate reduction length, alignment, and rotation.Postoperatively, patients
      begin hip and knee range-of-motion exercises without immobilization. Touch-down
      weight-bearing with crutches is used until callus formation is seen on
      radiographs, usually in 6 to 8 weeks. The plate can be removed 6 months after the
      index surgery.

PMID- 30233937
TI  - Intraoperative Monitoring of Epiphyseal Perfusion in Slipped Capital Femoral
      Epiphysis: Surgical Technique.
AB  - Introduction: Intraoperative monitoring of epiphyseal perfusion in slipped
      capital femoral epiphysis (SCFE) is a procedurally simple and readily accessible
      percutaneous technique to accurately guide decision-making and help to prevent
      osteonecrosis. Indications & Contraindications:  Step 1 Patient Preparation and
      Positioning: Following anesthesia induction, position the patient and assess the
      physeal stability fluoroscopically to determine the need for a reduction. Step 2
      Guidewire Placement: Place a 3.2-mm threaded guidewire from the anterolateral
      aspect of the femur to provide initial stability of the slipped epiphysis. Step 3
      Initial Screw Insertion: Insert a cannulated 7.0-mm stainless steel screw over
      the guidewire to a point just past the physis. Step 4 Preparation and Insertion
      of the ICP Probe: Once the screw has been inserted to obtain provisional
      stability of the physis, remove the guidewire and insert a sterile ICP probe down
      the screw shaft to assess the epiphyseal perfusion. Step 5 Hip Decompression: If
      a perfusion pressure and waveform cannot be obtained, perform decompression of
      the hip capsule by either aspiration or capsulotomy. Step 6 Epiphyseal Perfusion
      Reassessment: Following the capsulotomy, reinsert the ICP probe and reassess the
      epiphyseal perfusion. Step 7 Final Screw Advancement: Once epiphyseal blood flow
      can be confirmed, reintroduce the guidewire to its previous depth and advance the
      screw to the final measured depth. Results: Utilizing this technique over a 5
      year period, >35 patients were treated with the described technique, and 23 of
      them, including 29 hips, were included in our referenced prospective study3.
      Pitfalls & Challenges: 

PMID- 30233938
TI  - Step-Cut Ulnar Shortening Osteotomy for Ulnar Impaction Syndrome.
AB  - Introduction: The step-cut ulnar shortening osteotomy for the treatment of ulnar
      impaction syndrome is a safe, reliable, and less expensive technique that uses a
      7-hole 3.5-mm standard neutralization plate and a lag screw for fixation, thus
      avoiding the need for the special instrumentation that other ulnar shortening
      techniques require. Indications & Contraindications:  Step 1 Preoperative
      Planning: Perform a physical examination and obtain imaging studies to identify
      all associated abnormalities. Step 2 Wrist Arthroscopy Video 1: Verify the
      diagnosis of ulnar impaction syndrome and treat concurrent intra-articular
      abnormalities. Step 3 Incision for the Ulnar Shortening Osteotomy Video 2: Make a
      longitudinal skin incision along the distal third of the ulna. Step 4 Design the
      Step-Cut Ulnar Shortening Osteotomy Video 2: Design the step-cut ulnar shortening
      osteotomy. Step 5 Perform the Step-Cut Ulnar Shortening Osteotomy Video 2: Create
      the step-cut ulnar shortening osteotomy using an oscillating saw. Step 6 Fixation
      of the Osteotomy Video 3: Fix the osteotomy with a lag screw and volar plate.
      Step 7 Wound Closure: Meticulously close the wound in layers. Step 8
      Postoperative Care: Protect the affected arm for the first 6 weeks. Results: In
      our original study, 164 patients with symptomatic ulnar impaction syndrome were
      treated with a step-cut ulnar shortening osteotomy using a volar 3.5-mm standard
      neutralization plate and a lag screw14. Pitfalls & Challenges: 

PMID- 30233939
TI  - Anatomic Double-Bundle Posterior Cruciate Ligament Reconstruction.
AB  - The posterior cruciate ligament (PCL) is the main posterior stabilizer of the
      knee. It is composed of 2 bundles, the larger anterolateral bundle (ALB) and the
      smaller posteromedial bundle (PMB). The 2 bundles were historically believed to
      function independently, with the ALB predominantly being an important stabilizer
      in flexion and the PMB being a stabilizer mainly in extension. However, a recent
      biomechanical study1 noted a codominant relationship between these 2 bundles. The
      anatomic single-bundle PCL reconstruction, focusing on reconstruction of the
      larger ALB, is the most commonly performed procedure. Because of the residual
      posterior and rotational tibial instability after a single-bundle reconstruction
      and the inability to restore the normal knee kinematics, an anatomic double
      bundle PCL reconstruction has been proposed in an effort to recreate both bundles
      using the native footprint, thereby restoring the normal knee kinematics. The
      anatomic double-bundle PCL reconstruction has demonstrated improved subjective
      and objective patient outcomes with a low complication rate. Indications for PCL
      reconstruction are isolated symptomatic acute grade-III PCL tears, combined
      multiligament lesions, or acute grade-III PCL tears combined with repairable
      meniscal body or root tears. For chronic PCL tears, indications include
      functional limitations due to the PCL tear (e.g., difficulty with deceleration,
      incline descent, or stairs) and comparative PCL stress radiographic laxity of >8
      mm in a symptomatic patient. The steps of this procedure include (1) correct
      patient positioning to allow for good accessibility of both sides of the joint;
      (2) graft preparation (Achilles tendon [ALB] and tibialis anterior [PMB]
      allografts are used); (3) creation of femoral tunnels (11 mm for the ALB adjacent
      to the cartilage and 7 mm for the PMB with a 2-mm bone bridge); (4) tibial tunnel
      creation (12-mm diameter, 7 mm anterior to the so-called champagne-glass drop
      off); (5) graft fixation and tibial graft passage (a metal screw for the ALB and
      a bioabsorbable screw for the PMB, with the screws away from the bone bridge to
      avoid bone bridge breakage); and (6) tibial fixation (the grafts are
      independently fixed with the knee at 90 degrees  of flexion (ALB) and extension
      (PMB) with screws and washers on the medial side of the tibia. Three prospective
      randomized studies18,19,23 suggested that, while clinical outcomes are similar
      between both isolated transtibial reconstruction techniques, the objective
      measures of postoperative side-to-side posterior translation and objective
      International Knee Documentation Committee scores were significantly improved
      with double-bundle compared with single-bundle PCL reconstructions.

PMID- 30233941
TI  - The Circumferential Graft Technique for Treatment of Chronic Multidirectional
      Ligamentous Elbow Instability.
AB  - Introduction: The circumferential graft technique1,2 represents a potential
      option for the treatment of multidirectional ligamentous elbow instability using
      a single tendon graft (Video 1). Indications & Contraindications:  Step 1 Perform
      a Medial and Lateral Approach: Approach the elbow joint through either a single
      posterior skin incision or separate lateral and medial incisions. Step 2 Drill
      the Bone Tunnels: Create humeral and ulnar bone tunnels for circumferential graft
      placement. Step 3 Place the Graft: Use a plantaris allograft, which we recommend;
      however, a semitendinosus autograft may also be used. Step 4 Close the Wound:
      Ensure that meticulous wound closure is achieved as it is key to preventing
      postoperative complications such as superficial or deep infection and persistent
      seroma. Results: As multidirectional instability represents a rather rare
      complication following ligamentous elbow dislocation, clinical data regarding the
      circumferential graft technique are scarce1,2. Pitfalls & Challenges: 

PMID- 30233940
TI  - Total Elbow Arthroplasty: Why and How.
AB  - Introduction: Elbow arthroplasty is a relatively infrequent orthopaedic procedure
      that can be performed in multiple ways according to the type of prosthesis that
      is used and the needs of the individual patient. Indications & Contraindications:
      Step 1 Preparation and Positioning of the Patient: Place the patient in the
      lateral decubitus position or in the supine position with the arm draped,
      allowing for easy manipulation of the elbow during the procedure. Step 2
      Incision: Palpate and mark the local osseous landmarks, ulnar nerve, and
      incision, and then make a posterior incision to allow 360 degrees  access to the
      elbow joint as well as to allow decompression or transposition of the ulnar
      nerve. Step 3 Approach-The Superficial Layer: Perform the superficial approach,
      including a decompression of the ulnar nerve, and properly visualize the triceps
      tendon attachment on the proximal part of the ulna and both epicondyles. Step 4
      Approach-The Deep Layer: Mobilize the triceps to allow visualization of the
      articular surfaces of the ulna, humerus, and radius, while taking care to protect
      the ulnar nerve. Step 5 Preparation of the Osseous Structures: Prepare the
      humerus and ulna in conformance with the technique that is described for the
      prosthesis and take care to restore the anatomical flexion-extension axis of the
      elbow. Step 6 Placement of the Prosthesis: When all trial components are in
      place, reduce the joint to test the stability of the elbow. Step 7 Closure of the
      Elbow: When all of the definitive components of the total elbow arthroplasty are
      in place, close the surgical wound in layers as the anatomy is restored. Step 8
      Postoperative Care: After surgery, a wound dressing is applied and physical
      rehabilitation is started to maximize the functional outcome. Results: In our
      study of the mid-term results of a convertible total elbow arthroplasty, based on
      58 elbow arthroplasties, patients had significant improvement in range of
      movement, function, and pain at 6 months postoperatively8. Pitfalls & Challenges:

PMID- 30233942
TI  - Arthroscopic Reconstruction After Acute Acromioclavicular Separation Injuries.
AB  - Acute acromioclavicular (AC)-joint dislocations are common injuries of the
      shoulder girdle. Surgical repair is indicated for acute high-grade (Rockwood
      types IV, V, and VI) AC-joint injuries. The best treatment for type III is still
      controversial, but young and active patients with this type of injury might
      benefit from a surgical AC-joint stabilization. Surgery should be performed
      within the first 3 weeks after the injury since the biological healing potential
      decreases with time. Acute AC-joint separation is diagnosed by clinical
      examination and radiography. Vertical translation anteroposterior stress views
      with a 10-kg load are used to grade the injuries. Bilateral lateral stress
      (Alexander) views are used to evaluate dynamic horizontal translation
      qualitatively. Arthroscopic techniques for AC reconstruction have become more
      popular in recent years because they are minimally invasive; they allow treatment
      of concomitant glenohumeral lesions; and they can be performed in one step, with
      insertion of implants that do not have to be removed later. The arthroscopically
      assisted double-button technique with an additional AC cerclage was developed to
      stabilize the AC joint by internal bracing of the torn ligaments. The procedure
      consists of the following steps. Step 1: With the patient in the beach-chair
      position, a 2-cm incision is made on top of the clavicle and posterior and
      lateral viewing portals as well as an anteroinferior working portal are created.
      Step 2: With the arthroscope in the lateral portal, the subcoracoid bursa and the
      base of the coracoid are dissected with a radiofrequency ablation device through
      the anteroinferior portal. Step 3: Coracoclavicular drilling is done with use of
      a drill guide and under arthroscopic and image-intensifier control. After
      overdrilling of the Kirschner wires, Nitinol suture passers are introduced and
      retrieved via the anteroinferior portal. Step 4: Transclavicular and
      transacromial drill-holes are established for the AC cerclage. Step 5: The 2
      double-button devices are attached to the Nitinol suture passers, and the
      inferior buttons are shuttled through the clavicle and coracoid and then placed
      parallel to the coracoid base. Step 6: The sutures are tightened, and an
      anatomical vertical reduction of the AC joint is achieved. Step 7: A triangular
      acromioclavicular nonabsorbable cerclage tape is used for horizontal
      stabilization. Step 8: The clavicular incision is closed in 2 layers, including
      the repair of the deltotrapezoidal fascia and the arthroscopic portals, in a
      standard fashion. The combined arthroscopically-assisted and image-intensifier
      controlled double-button technique with an additional AC cerclage is a safe
      procedure that enables an anatomical reduction of the AC joint and yields good to
      excellent clinical results.

PMID- 30233943
TI  - Treatment of Radial Head Fractures with a Modular Metallic Radial Head
      Replacement.
AB  - Introduction: Radial head arthroplasty with a smooth-stemmed metallic modular
      implant is a reliable treatment option for patients with acute unreconstructible
      radial head fractures, and good clinical outcomes may be expected beyond 5 years
      of follow-up (Video 1). Indications & Contraindications:  Step 1 Preoperative
      Planning: Obtain a careful history and perform a physical examination along with
      appropriate imaging to facilitate appropriate treatment decisions. Step 2
      Operating Room Setup and Patient Positioning: Perform proper operating room setup
      and patient positioning, as they are required to gain access to all affected
      structures around the elbow in a safe and efficient manner. Step 3 Approach: Make
      a midline posterior skin incision with development of a full-thickness lateral
      fasciocutaneous flap or use a direct lateral incision; the deep interval is
      determined on the basis of the integrity of the LCL. Step 4 Radial Head Excision:
      Remove and preserve all fragments of the radial head for implant sizing. Step 5
      Implant Sizing: Implant a prosthesis that closely replicates the dimensions of
      the native radial head, which is the primary goal of the procedure. Step 6 Stem
      Broaching: Sequentially broach the canal until good cortical contact is achieved
      and undersize the definitive stem by 1 mm to allow implant movement within the
      canal and appropriate articulation with the capitellum. Step 7 Insertion of Trial
      Components and Final Radial Head Implant: With the selected trial in place,
      assess the radial head diameter, height, and articular congruency. Step 8 Closure
      and Repair of the LCL: Ensure proper repair of the LCL as it is essential to
      maintaining or restoring elbow stability. Step 9 Postoperative Protocol:
      Postoperative rehabilitation depends on the status of the collateral ligaments.
      Results: In a review of the cases of 55 patients at a mean follow-up of 8 years
      after radial head arthroplasty with a smooth-stemmed modular metallic prosthesis,
      Marsh et al.9. Pitfalls & Challenges: 

PMID- 30233944
TI  - Minimally Invasive Unilateral Laminectomy for Bilateral Decompression.
AB  - Introduction: Unilateral laminectomy for bilateral decompression (ULBD) is a
      recently popularized minimally invasive surgical technique for decompression of
      the spinal canal. Indications & Contraindications:  Step 1 Positioning Incision
      and Instruments Required: With the patient prone on the spinal table of your
      choice, use an image intensifier to determine the incision position and then
      position the retractor of your choice to identify the inferior aspect of the
      superior lamina. Step 2 Bone Removal: Begin the laminotomy on the approach side,
      drilling to identify the ligamentum flavum on the approach side, and remove bone
      up to the superior attachment of the ligamentum flavum. Step 3 Undercutting of
      the Spinous Process: To gain access to the contralateral side of the canal for
      bilateral decompression, remove enough of the spinous process to gain access to
      the midline and contralateral ligamentum flavum. Step 4 Identify the Superior
      Aspect of the Ligamentum Attachment: The superior aspect of the decompression
      usually corresponds with the superior ligamentum flavum attachment, except in
      certain cases such as when a facet joint cyst extends beyond the limits of the
      ligamentum flavum; removal of the upper limit of the ligamentum flavum provides
      an important landmark to confirm the superior limit of the decompression. Step 5
      Lateral Recess Decompression on the Ipsilateral Approach Side: Detach the
      ligamentum flavum from the facet joint on the approach side using a combination
      of angled curets and Kerrison rongeurs; a partial medial facetectomy, or removal
      of adequate facet hypertrophy, on the approach side is necessary to expose the
      traversing nerve root. Step 6 Decompression of the Contralateral Side of the
      Canal: Decompression of the thecal sac on the contralateral side of the canal is
      the potentially dangerous aspect of the procedure, with the highest risk of dural
      injury and a cerebrospinal fluid leak; thus, create enough room on the
      ipsilateral side so that instruments can be safely introduced into the canal for
      the contralateral decompression. Step 7 Hemostasis: Reducing the paraspinal
      muscle dissection substantially reduces iatrogenic muscle injury and blood loss,
      and oozing from the bone removal can be easily controlled with bone wax or a
      variety of hemostatic agents. Step 8 Closure: Closure of a unilateral muscle
      exposure is rapid and the use of wound drainage is very rare, further reducing
      operative time as well as exposure to complications related to wound drains and
      subsequent infection risk. Results: One of us (R.M.) and colleagues5 conducted a
      prospective randomized trial comparing ULBD with open laminectomy for
      degenerative lumbar spinal stenosis in 54 patients (27 in each arm of the study)
      treated from 2007 to 2009. Pitfalls & Challenges: 

PMID- 30233945
TI  - Anterior Approach for Ankle Arthrodesis.
AB  - End-stage ankle arthritis may be treated successfully with either an ankle
      arthrodesis or arthroplasty. Both surgical interventions have demonstrated
      success with regard to pain relief and function. Ankle arthrodesis is indicated
      for patients with recalcitrant ankle pain despite appropriate nonoperative
      intervention. Patients who have a history of posttraumatic arthritis from a high
      energy injury, soft-tissue compromise, limited range of motion, or deformity may
      be superior candidates for arthrodesis. The surgical technique can be undertaken
      with either an open or an arthroscopic approach. An open anterior approach with
      an anatomic precontoured locking plate is ideal for patients with deformity
      and/or bone loss. Additionally, the use of a precontoured plate assists with
      achieving a neutral alignment in both the coronal and the sagittal plane, which
      is critical to the long-term success of the procedure. No hardware, however,
      substitutes for appropriate surgical technique, which is the focus of this video
      article. The procedure includes the following steps:An anterior extensile
      incision is made immediately lateral to the anterior tibial tendon, extending to
      the level of the talonavicular joint.Dissection is taken with care to avoid the
      superficial peroneal nerve in the distal aspect of the incision. The extensor
      retinaculum is incised either longitudinally or in a z-shaped fashion to
      facilitate closure.Deep dissection may be taken through the sheath of the
      anterior tibial tendon, which substantially decreases the risk of injury to the
      deep neurovascular bundle. Alternatively, dissection may be taken through the
      extensor hallucis longus (EHL) to avoid violation of the anterior tibial tendon
      sheath. The neurovascular bundle is directly posterior to the EHL at the level of
      the ankle joint.The ankle joint is exposed, with the removal of tibial and talar
      osteophytes.The joint surfaces are prepared.The precontoured ankle arthrodesis
      plate, which is used to improve alignment, is positioned and placed.Compression
      is achieved using the "Achilles tension band technique," which furthers
      compression through the ankle.An additional transarticular screw is placed. The
      expected outcome of the procedure, based on recent clinical outcomes, is osseous
      union, and the rate of union has been reported to range from 91% to 96%.
      Improvement in function and pain relief are associated with a successful
      arthrodesis. Despite a slow deterioration of functional outcomes and radiographic
      progression of arthritis, clinical improvement with a high rate of patient
      satisfaction has been noted at a mean of 9 years postoperatively.

PMID- 30233946
TI  - Reorientational Proximal Femoral Osteotomies for Correction of Hip Contractures
      in Children with Arthrogryposis.
AB  - Introduction: Reorientational osteotomy of the proximal part of the femur for
      children with arthrogryposis repositions the various arcs of hip motion into a
      more functional sphere of motion, addressing the hip contractures that otherwise
      are the main mechanical impediments to ambulation. Indications &
      Contraindications:  Step 1 Preoperative Assessment: Determine hip range of motion
      clinically and obtain radiographs to confirm that the hips are located and there
      are no unusual structural abnormalities. Step 2 Patient Positioning and Draping:
      Position the patient supine with a bump at the sacrum, and drape to allow access
      to both hips simultaneously. Step 3 Initial Percutaneous Anterior Hip Release:
      Perform an initial anterior hip release for patients with a palpable soft-tissue
      flexion contracture. Step 4 Surgical Approach to the Proximal Part of the Femur:
      Make a standard approach to the lateral aspect of the proximal part of the femur.
      Step 5 Blade-Plate Positioning: Position a guidewire for the appropriate
      correction; then cut a track for the blade plate with a seating chisel. Step 6
      Wedge-Shaped Intertrochanteric Osteotomy: Perform 2 intertrochanteric osteotomy
      cuts to provide cut surfaces that, when joined together, will position the lower
      extremity optimally. Step 7 Applying the Blade Plate and Closure: Impact the
      blade plate into the proximal fragment and secure it to the distal fragment. Step
      8 Postoperative Management: Apply a Petrie cast, and instruct the parents on how
      to maintain hip motion. Step 9 Plate Removal: Remove the blade plate on an
      outpatient basis 12 to 18 months after the osteotomy, through the smallest
      incision possible to allow a quicker recovery. Results: We performed
      reorientational osteotomies on 68 consecutive children with arthrogrypotic
      multiplanar hip contractures over a 5-year span, and 65 were followed for at
      least 2 years; 54 of these patients had a bilateral hip contracture, for a total
      of 119 reorientational osteotomies. Pitfalls & Challenges: 

PMID- 30233947
TI  - Open Reduction and Internal Fixation for Lateral Unicondylar Distal Humeral
      Fractures.
AB  - Introduction: Unicondylar distal humeral fractures are uncommon, partially intra
      articular fractures (OTA/AO type B1) that are among the most complex fractures to
      treat1,2; however, most displaced distal humeral fractures, including lateral
      unicondylar distal humeral fractures2-5, can be effectively managed with open
      reduction and internal fixation. Indications & Contraindications:  Step 1
      Preparation of the Operating Room and the Patient: Perform sterile preparation,
      have the patient brought into the operating room, induce anesthesia, and place
      the patient in the lateral decubitus or supine position before sterile draping.
      Step 2 Approach to the Fracture: Make a lateral incision, expose the lateral
      distal part of the humerus, identify the ulnar nerve if necessary, visualize the
      fracture fragments, and debride the fracture site. Step 3 Reduction of the
      Fracture: Reduce the fracture and fix it temporarily. Step 4 Plate Fixation of
      the Fracture: Determine the plate length; position the plate posterolaterally,
      posteriorly, or laterally; insert screws; remove provisional Kirschner wires; and
      obtain intraoperative images. Step 5 Final Radiographic Imaging: Make
      anteroposterior and lateral radiographic images to confirm reduction and adequate
      anatomic alignment of the elbow and the position of the hardware. Step 6 Closure
      of the Wound: Deflate the tourniquet, irrigate the wound, and apply postoperative
      dressings. Results: The detailed outcome for a cohort of 24 patients who
      underwent this procedure has been reported elsewhere6. Pitfalls & Challenges: 

PMID- 30233948
TI  - Arthroscopic Repair of Subscapularis Tendon Tears.
AB  - The subscapularis is the largest and strongest muscle of the rotator cuff, and it
      plays an essential role in global shoulder function. Beyond its primary function
      as an internal rotator, the subscapularis also acts to pull the humeral head
      posteriorly on the glenoid and is an important dynamic and static anterior
      stabilizer of the glenohumeral joint. In comparison with tears of the tendons of
      the rest of the rotator cuff, isolated tears of the subscapularis have a tendency
      for both early retraction and fatty infiltration. Consequently, full-thickness
      tears of the subscapularis tendon generally require surgical management.
      Arthroscopic suture-anchor repair allows anatomic reconstruction of the anterior
      aspect of the rotator cuff, with all of the benefits of arthroscopic surgery. The
      principal steps of this procedure include (1) verifying the subscapularis tear
      and identifying any concomitant lesions during diagnostic arthroscopy, (2)
      exposing the subscapularis tendon, (3) releasing tendon adhesions and so enabling
      anatomic reduction, (4) placing suture anchors at the anatomic subscapularis
      footprint on the lesser tuberosity and anatomically repairing the subscapularis
      tendon to its anatomic insertion, and (5) performing biceps tenodesis or
      tenotomy, if indicated. Postoperatively, patients with an isolated subscapularis
      tear are managed with immobilization in a sling for 6 weeks, while those with
      combined anterosuperior rotator cuff tears are managed with an abduction pillow.
      Arthroscopic subscapularis reconstruction provides a good structural repair,
      substantially restores shoulder mobility and strength, reduces pain, and results
      in high levels of patient satisfaction and return of shoulder function as
      measured by functional outcome scores.

PMID- 30233949
TI  - Medial Gastrocnemius Flap in the Course of Treatment for an Infection at the Site
      of a Total Knee Arthroplasty.
AB  - Introduction: The pedicled medial gastrocnemius flap provides a robust coverage
      option for most soft-tissue deficiencies over the distal anterior aspect of the
      knee encountered in the setting of an infection after total knee arthroplasty.
      Indications & Contraindications:  Step 1 Patient Positioning: Position the
      patient supine with an ipsilateral sterile thigh tourniquet to allow room for
      harvest of a split-thickness skin graft as needed. Step 2 Revision Arthroplasty
      for Infection: Perform the arthroplasty to address the underlying deep infection
      (e.g., irrigation and debridement with exchange of modular components, component
      removal with antibiotic spacer placement, antibiotic spacer exchange, or second
      stage reimplantation) prior to the medial gastrocnemius flap that is utilized for
      soft-tissue coverage. Step 3 Incision and Approach for the Medial Gastrocnemius
      Flap: Use one of two different surgical approaches for the exposure and elevation
      of the medial gastrocnemius muscle and the identification of its vascular
      pedicle: the medial approach or the posterior midline approach. Step 4 Elevation
      of the Medial Gastrocnemius Flap: Protect the sural artery pedicle in the
      popliteal fossa because it is key to raising a viable medial gastrocnemius flap.
      Step 5 Transposition and Insetting of the Flap Over the Defect: Rotate the flap
      and transpose it anteriorly over the defect either through a subcutaneous tunnel
      or by dividing the intervening skin bridge. Step 6 Closure Skin-Grafting and
      Dressing Application: Complete the layered skin closure and place a split
      thickness skin graft over the remaining exposed muscle flap and a nonadherent
      compressive bolster dressing or negative-pressure device over the skin graft to
      prevent hematoma under the skin graft. Step 7 Postoperative Care: Progress range
      of motion of the knee once the flap and graft show evidence of survival, while an
      appropriate antibiotic regimen is completed. Results: We recently reported the
      largest English-language series, to our knowledge, of medial gastrocnemius flaps
      performed for soft-tissue coverage in the course of treatment for infection after
      total knee arthroplasty13. Pitfalls & Challenges: 

PMID- 30233950
TI  - Single-Level Cervical Disc Arthroplasty with a Bryan Device.
AB  - Introduction: The anterior cervical approach for discectomy with modified
      distraction and milling tools (Video 1) provides an ideal method for surgical
      treatment of symptomatic discogenic disease and subsequent placement of an
      arthroplasty device. Indications & Contraindications:  Step 1 Patient
      Positioning: Position the patient supine on a radiolucent table that allows for
      anteroposterior and lateral fluoroscopic imaging. Step 2 Surgical Approach: Use a
      standard Smith-Robinson approach to the anterior cervical spine at the index
      level of pathological involvement. Step 3 Discectomy Distraction and Initial End
      Plate Preparation: Perform the initial discectomy with a modified distraction
      technique; then perform the index neurological decompression followed by
      bilateral neuroforaminal decompression. Step 4 End-Plate Preparation: Size the
      end plates and eventual arthroplasty device, and mill the end plates. Step 5
      Insertion of Arthroplasty Device: Prepare the arthroplasty device and insert it.
      Step 6 Imaging and Wound Closure: Close the wound and incision in a fashion
      typical for a Smith-Robinson-type approach. Step 7 Postoperative Care:  Results:
      Pain, neurological, and functional outcomes in the immediate perioperative period
      are at least similar, if not superior, to those achieved with arthrodesis, as are
      the outcomes over the ensuing months and years. Pitfalls & Challenges: 

PMID- 30233951
TI  - Open Reduction and Internal Fixation of a Middle-Third Clavicle Fracture with a
      Superior Plate.
AB  - Open reduction and internal fixation has become a reliable technique to treat
      complex middle-third clavicle fractures (AO/OTA B-15). Nonoperative treatment of
      these fractures may result in higher rates of symptomatic malunion, nonunion,
      dissatisfaction with cosmetic appearance, and even dysfunction and muscular
      weakness. Risk factors such as substantial displacement or comminution, far
      lateral fractures, fractures in the elderly, open fractures, or those occurring
      in polytrauma scenarios are appropriate indications for surgery. The aim of the
      procedure is to reconstitute the initial curvature and length of the clavicle,
      restore a normal connection from the arm to the axial skeleton, and provide
      stable fixation of the proximal and distal fragments, to allow an immediate full
      range of motion during rehabilitation. The procedure includes the following
      steps. Step 1: Place the patient in a beach-chair, semi-sitting position.Step 2:
      Make a transverse skin incision along the anteroinferior aspect of the
      clavicle.Step 3: Expose the fracture site, identify and prepare the fragments
      unless they are comminuted, and preserve soft-tissue attachments to the extent
      possible.Step 4: Reduce the fragments by direct or indirect manipulation, and
      maintain the reduction with clamps, Kirschner wires, or mini-fragment plates.
      Consider bridging comminuted zones to allow secondary fracture-healing.Step 5:
      Apply a contoured plate to the superior or anterior surface of the clavicle, and
      obtain at least 6 cortices of fixation on each side with strategic nonlocking and
      locking screws. The working length of the plate is more important than the number
      of screws or cortices.Step 6: Obtain a single intraoperative anteroposterior
      radiograph of the clavicle.Step 7: Separately close the wound in layers
      (deltotrapezial fascia, platysma, and skin). Apply sterile dressings and a sling.
      The patient is discharged home on the same day if the injury is isolated, and a
      full range of motion of the affected shoulder is allowed immediately. The patient
      is expected to regain full function and strength of the arm once healing occurs.

PMID- 30233952
TI  - Porous Tantalum Femoral Metaphyseal Cones for Large Femoral Bone Defects in
      Revision Total Knee Arthroplasty.
AB  - Introduction: The use of porous tantalum metaphyseal cones provides reliable
      metaphyseal support and fixation to help restore the joint line in difficult
      revision total knee arthroplasties (TKAs) in patients with large femoral bone
      defects. Indications & Contraindications:  Step 1 Preoperative Planning: Adequate
      preoperative radiographs are important to determine the approximate size of the
      femoral bone defect prior to surgery. Step 2 Incision and Exposure: Adequate
      exposure during revision knee surgery is key for the safe removal of implants and
      to minimize bone loss. Step 3 Component Removal: It is essential to disrupt the
      prosthesis-cement interface before attempting to extract well-fixed components.
      Step 4 Establishing a Tibial Platform: The first step in revision knee
      reconstruction is to establish a stable tibial platform. Step 5 Reconstruction of
      the Femur: Restoring the joint line and posterior condylar offset are the goals
      of femoral reconstruction. Step 6 Intraoperative Assessment of Femoral Bone Loss:
      Thoroughly assess the quality, quantity, and location of the remaining cancellous
      and cortical bone to determine the proper technique for reconstruction. Step 7
      Selecting the Appropriate Metaphyseal Cone and Shaping the Femoral Metadiaphysis
      for the Femoral Cone: There are different sizes and shapes of metaphyseal cones
      that can be used when addressing large femoral bone defects. Step 8 Implanting
      the Actual Porous Metaphyseal Cone: During the final impaction of the femoral
      metaphyseal cone, take care to not cause a fracture. Step 9 Final Trial and
      Cementing of the Final Stemmed Femoral Component: Place the final stemmed femoral
      component through the metaphyseal cone and cement it into place. Step 10
      Postoperative Protocol: If a stable construct was achieved, the patient may bear
      weight as tolerated with no specific restrictions on range of motion. Results: We
      recently performed a retrospective review of the midterm outcomes at mean of 5
      years (range, 2 to 10 years) after 159 consecutive revision TKAs with a porous
      metal femoral metaphyseal cone in 157 patients with large bone defects 4.
      Pitfalls & Challenges: 

PMID- 30233954
TI  - Arthroscopic Tenodesis of the Long Head of the Biceps Tendon.
AB  - Lesions of the long head of the biceps brachii tendon (LHBT) are a common source
      of shoulder pain and dysfunction. Although the exact role of the LHBT in shoulder
      biomechanics is not clearly understood, pathological involvement of this tendon
      is a well-known pain generator and frequently the clinical presentation consists
      of both anterior pain and flexion loss. The initial treatment for lesions of the
      LHBT should be nonoperative, but if that fails or if the LHBT lesion is combined
      with rotator cuff lesions or other lesions that need to be repaired surgically,
      surgical intervention is indicated. Tenotomy and tenodesis of the LHBT are 2
      classic representative treatments with confirmed results. Tenodesis may be
      especially beneficial for patients younger than 50 years old or those who perform
      strenuous labor. The procedure is performed arthroscopically with the following
      steps. Step 1: A standard posterior viewing portal and an anterior working portal
      are made. Step 2: After confirmation of the LHBT lesion inside the glenohumeral
      joint, number-1 polydioxanone (PDS) suture is passed through the tendon before
      tenotomy is performed just above the superior labrum. Step 3: The tenotomized
      tendon is pulled out through the anterior portal by gentle traction on the
      attached PDS suture. A Krackow whip-stitch with nonabsorbable suture is made in
      the tendon. Step 4: A 7 to 8-mm drill-hole is made in the intertubercular groove
      of the humeral head just proximal to the insertion of the subscapularis tendon.
      Step 5: The suture is tightly tied to the distal hole of a 7.0-mm BioComposite
      SwiveLock Interference Screw (Arthrex). Step 8: The interference screw with the
      tenotomized end is inserted into the drill-hole. LHBT tenodesis lessens the
      cosmetic problem of Popeye deformity that is seen after tenotomy. Also, elbow
      motor power including flexion and supination is preserved.

PMID- 30233953
TI  - Applied Anatomy of the Direct Anterior Approach for Femoral Mobilization.
AB  - Introduction: Study of the anterior anatomy of the hip reveals specific aspects
      that are crucial to success in performing both the surgical approach to the hip
      and mobilization of the femur. In this article, we present the relevant anatomy
      and our operative technique. Indications & Contraindications:  Step 1 The
      Anterior Anatomy of the Hip Video 1: Review the anatomy of the hip as it relates
      to the surgical technique as doing so is essential to understanding the surgical
      technique6. Step 2 Approach to the Anterior Aspect of the Hip Video 2: Review the
      surgical approach to the hip. Step 3 Release of the Capsule Video 3: In the first
      step of femoral mobilization, release the superior-posterior capsule. Step 4
      Release of the Conjoined Tendon and Piriformis Flip Video 4: If sufficient
      elevation of the femur is not achieved with release of the capsule, perform
      rotator visualization and serial release. Results: Our prospective, nonrandomized
      study compared DAA THA using our technique for femoral mobilization with the
      posterior approach THA12. Pitfalls & Challenges: 

PMID- 30233955
TI  - The Pelvic Bridge: A Subcutaneous Approach for Anterior Pelvic Fixation.
AB  - Introduction: An alternative method to external fixation for the treatment of
      unstable anterior pelvic ring injuries, termed the pelvic bridge technique,
      provides equivalent results with fewer complications and is performed using
      occipital cervical rods subcutaneously, with fixation into the iliac wings and
      parasymphyseal bone. Indications & Contraindications:  Step 1 Preoperative
      Planning: For preoperative planning, review the appropriate imaging, including
      radiographs and computed tomography (CT) scans, to mesh the findings on imaging
      to the clinical picture of the patient and ensure that the patient meets
      operative criteria and that none of the contraindications are present. Step 2
      Patient Positioning: Position the patient to facilitate anterior and posterior
      fixation. Step 3 Approach: Make the incisions necessary to expose the osseous
      contour where fixation will be utilized. Step 4 Contouring the Plate-Rod
      Construct: Carefully contour the plate-rod construct, which is necessary to
      minimize postoperative complications. Step 5 Passing the Plate-Rod Construct: Use
      care when inserting the rod as doing so will help to avoid neurovascular
      complications. Step 6 Achieving Adequate Reduction: To recreate pelvic stability,
      the pelvic ring needs to heal in as close to anatomic position as possible and
      there are multiple methods that help to obtain an adequate reduction. Step 7
      Fracture Fixation: Multiple constructs may be used to stabilize the anterior
      pelvic ring, but the fundamental principle is to attach the 2 hemipelves to
      achieve stability, and the location where fixation can be achieved depends on the
      fracture pattern. Step 8 Wound Closure: Ensure meticulous closure to reduce the
      chance of infection and achieve appropriate soft-tissue coverage over hardware.
      Step 9 Rehabilitation: Early mobilization is a fundamental goal of this
      procedure, but the time to full weight-bearing is dependent on fracture
      characteristics and healing. Results: Anterior pelvic internal fixation (APIF)
      using the pelvic bridge technique has been demonstrated to have significantly
      fewer complications than APEF2. Pitfalls & Challenges: 

PMID- 30233956
TI  - Congratulations to 2016 EST Award Winners.

PMID- 30233957
TI  - A Practical Guide to the Use of the Anterolateral Thigh Flap.
AB  - Introduction: The anterolateral thigh (ALT) flap allows for healthy, reliable,
      vascularized, soft-tissue coverage of extremity or axial defects of traumatic or
      acquired deformities. Indications & Contraindications:  Step 1 Positioning and
      Markings: Place the patient in the supine position, which allows for flap harvest
      and typically does not require any position changes (Fig. 1), and then mark the
      septum between the vastus lateralis and rectus femoris, which facilitates harvest
      of this flap (Video 1). Step 2 Perforator Dissection: Dissect this flap, which is
      relatively straightforward and rapid after identifying the perforating vessels
      (Video 2, Fig. 4). Step 3 Pedicle Dissection: Trace the course of the descending
      branch of the lateral femoral circumflex proximally and determine the maximum
      pedicle length and vessel diameter for microvascular anastomoses (Figs. 5 and 6).
      Step 4 Flap Harvest and Recipient Vessels: Confirm the dimensions of the flap
      prior to final harvest of the flap, and pay special attention to the recipient
      arterial inflow and venous outflow to ensure success. Step 5 Microvascular
      Anastomoses: When performing this flap as a microvascular free flap, identify and
      prepare suitable vessels for tissue transfer (Fig. 13). Step 6 Flap Inset: Pay
      special attention to the flap inset to ensure that there is no mechanical
      obstruction to the pedicle and that the inset allows for the anticipated
      postoperative edema (Figs. 14 and 15). Step 7 Donor Site Closure: Close the donor
      site for this flap, which is well tolerated and easily concealed (Fig. 16). Step
      8 Flap Monitoring and Postoperative Care: Postoperative monitoring is critical to
      identify any potential vascular compromise early and maximize successful
      outcomes4. Results: The ALT is a highly successful and reliable flap that has
      become a workhorse of reconstructive microsurgery5. Pitfalls & Challenges: 

PMID- 30233958
TI  - SuperPath: The Direct Superior Portal-Assisted Total Hip Approach.
AB  - The supercapsular percutaneously assisted total hip (SuperPath; MicroPort)
      approach is a direct superior portal-assisted approach for total hip arthroplasty
      (THA) that utilizes the interval between the gluteus minimus and the piriformis
      to access the hip capsule. The technique was developed to promote early
      mobilization, greater range of motion, and improved pain control. The major steps
      of this procedure are as follows: Step 1: Patient positioning. The patient is in
      the standard lateral decubitus position with the involved leg in the "home
      position," that is, 45 degrees  to 60 degrees  of flexion, 20 degrees  to 30
      degrees  of internal rotation, and slight adduction by elevating the foot on a
      padded Mayo stand. Step 2: Surgical exposure. A skin incision is made from the
      tip of the greater trochanter 6 to 8 cm proximally in line with the femur in the
      home position, the gluteus maximus muscle is split by blunt dissection in line
      with the fibers, and the gluteus medius and minimus are retracted anteriorly and
      the piriformis tendon is retracted posteriorly to access to the capsule without
      dissecting any muscles. Step 3: Capsular incision. The capsule is incised along
      the path of the skin incision from the saddle of the femoral neck to 1 cm
      proximal to the acetabular rim. Step 4: Femoral preparation. A channel is created
      in the superior aspect of the femoral neck from the femoral canal to the center
      of the femoral head, using reamers, a round osteotome, and a curet. Step 5:
      Femoral broaching. Sequential femoral broaches are then used to complete the
      preparation and size the proximal femoral canal while the head and neck remain
      intact. Step 6: Neck resection. The femoral neck osteotomy is performed level
      with the broach neck, and Schanz pins are used to rupture the ligamentum teres
      and remove the femoral head. Step 7: Acetabular preparation and placement.
      Acetabular preparation and cup impaction are done through a portal without
      needing release of the iliotibial band or remaining external rotators. A sharp
      Romanelli self-retaining retractor (Innomed) and modified Zelpi self-retaining
      retractor (Life Instruments) are used. Step 8: Trial reduction. Trial reduction
      is completed using a bone hook and a T-handle to gently manipulate the femur.
      Step 9: Final implant assembly. Liner impaction is completed through the portal,
      and the remaining components are implanted. Step 10: Closure. Closure is limited
      to the capsule, fat, and skin, since no muscles are dissected during this
      procedure. A recent multicenter study describing nearly 500 SuperPath THAs noted
      a 30-day all-cause readmission rate of 2.3% and a transfusion rate of 3.3%5. The
      average length of stay was 1.6 days, with 91% of patients discharged home; 4.1%,
      to skilled nursing facilities; 3.8%, to home care; and 0.6%, to inpatient
      physical therapy facilities6.

PMID- 30233959
TI  - Technique for Insertion of the Conventus Cage for Distal Radial Fracture
      Fixation.
AB  - Introduction: Use of the intramedullary Conventus DRS Cage and fragment-specific
      screw fixation of distal radial fractures minimizes soft-tissue trauma, leading
      to earlier and improved wrist and finger motion while reducing traditional
      complications seen with internal fixation of distal radial fractures. Indications
      & Contraindications:  Step 1 Reduce the Fracture: Reduce the fracture with closed
      or, if necessary, open methods to achieve anatomic restoration of articular
      congruity, radial inclination, radial length, volar tilt, and coronal shift. Step
      2 Provisionally Stabilize the Fracture: Provisionally stabilize the reduced
      fracture for insertion of the cage and fragment-specific screws with either
      longitudinal finger-trap traction or longitudinal Kirschner wires. Step 3 Prepare
      for Cage Fixation: Prepare the distal part of the radius for cavity preparation
      and insertion of the Conventus DRS Cage. Step 4 Insert the Conventus DRS Cage:
      Insert the previously chosen small or large Conventus DRS Cage. Step 5 Fix the
      Fracture Fragments: Anatomically fix the fracture fragments to the cage and
      radial shaft. Step 6 Confirm Fracture Stability: Move the wrist through a full
      range of motion while assessing fluoroscopically whether the fracture has been
      stabilized with the cage-and-screw construct. Step 7 Close the Wound: Close the
      skin incision and cutdown wounds and apply dressings. Results: The Conventus DRS
      Cage has been used for treatment of distal radial fractures in the U.S. for >3
      years. Pitfalls & Challenges: 

PMID- 30233960
TI  - Treatment of Hip Flexion Contractures with Psoas Recession Through the Middle
      Window of the Ilioinguinal Approach.
AB  - Introduction: The ilioinguinal approach for psoas recession over the pelvic brim
      allows for direct visualization and protection of the femoral nerve while
      preserving hip flexion strength. Indications & Contraindications:  Step 1 Patient
      Positioning Preoperative Assessment and Draping: With the patient supine and
      anesthetized, perform the Thomas test, administer antibiotics, and drape to
      provide access to the inferior aspect of the abdomen, ilioinguinal region, and
      lower limb. Step 2 Superficial Dissection: Mark the osseous landmarks, draw a
      line connecting the anterior superior iliac spine to the pubic tubercle, and make
      a bikini incision along this line. Step 3 Deep Dissection: Incise the external
      oblique aponeurosis and internal oblique and transverse abdominal muscles from
      the anterior superior iliac spine to the pubic tubercle, leaving a 2-mm cuff of
      tissue. Step 4 Psoas Recession: After protecting the femoral nerve, confirm the
      identity of the psoas with 3 tests and transect it with cautery. Step 5
      Postoperative Management: Physical therapy is initiated immediately and includes
      static and dynamic hip extension exercises that stretch the anterior hips
      structures. Results: Hip flexion contracture is a debilitating condition that
      affects many patients with spastic paresis or prior hip trauma. Pitfalls &
      Challenges: 

PMID- 30233961
TI  - Single-Leg Spica Cast Application for Treatment of Pediatric Femoral Fracture.
AB  - Use of a single-leg spica cast for femoral fractures in ambulatory children 1 to
      5 years of age facilitates care and mobilization of the patient. It may allow a
      shorter duration of cast treatment than is possible with a traditional one and
      one-half-leg spica cast, particularly in patients 1 to 3 years of age. The single
      leg spica is indicated for children who are small enough to be lifted safely in
      the cast and who have an isolated, closed, low-energy femoral shaft fracture. The
      procedure consists of the following steps:Step 1: Obtain adequate sedation.
      General anesthesia should be used in the operating room, whereas conscious
      sedation may be used in the emergency or procedure room setting. The location of
      the procedure should be determined by available resources.Step 2: Determine the
      position of optimal alignment by visual examination of the thigh and leg. If
      intraoperative imaging is available, assess fracture stability by performing the
      telescope test described by Thompson et al.1-i.e., by gently applying axial load
      to the thigh to assess for shortening under fluoroscopic monitoring. Shortening
      of >3 cm reflects substantial periosteal stripping and is associated with an
      increased risk of loss of reduction in the cast. Alternative stabilization
      techniques should be considered for grossly unstable fractures with a positive
      telescope test. Use of intramedullary nails, external fixation, or traction with
      delayed cast application may decrease the risk of excessive shortening or
      unacceptable angulation of the fracture in the cast.Step 3: Apply a stockinette
      or waterproof pantaloons cast liner to the torso and involved lower
      extremity.Step 4: Position the patient on a spica-cast application table, which
      provides a support under the thorax and head with a strut that supports the spine
      and pelvis to the sacrum, allowing application of the cast material to the pelvic
      area and involved extremity. Position the patient on the table with the involved
      extremity flexed 30 degrees  to 60 degrees  at the hip and 30 degrees  to 60
      degrees  at the knee and the contralateral leg supported. Greater flexion makes
      it easier to fit the child into a car seat or high chair and to carry him/her on
      the caretaker's hip, whereas flexing the hip and knee less allows the patient to
      bear weight more easily. However, Illgen et al.2 found knee flexion of <50
      degrees  to be associated with an increased risk of reduction loss. More proximal
      fractures are better treated with greater hip flexion because of their tendency
      to drift into apex anterior angulation.Step 5: Overwrap the cast liner from
      nipple line to ankle with cotton or synthetic undercast padding to prevent
      pressure sores. Some families prefer waterproof cast padding as it allows the
      child to be immersed for bathing, but it provides less padding at pressure points
      and increases the cost of the cast.Step 6: Apply fiberglass or plaster cast
      material starting 1 in (2.5 cm) below the edge of the cast padding and ending 1
      in above the malleoli to allow the edges of the cast to be adequately padded when
      the liner is folded back.Step 7: Apply an iliac crest mold to stabilize the hip,
      and apply an anterior and valgus mold to the involved thigh to recreate the
      anterior bow and address the tendency of femoral shaft fractures to drift into
      varus.Step 8: Trim and finish the cast. Inspect the groin region for rough edges
      and trim them as needed using the cast saw or bandage scissors. Cast edges should
      be "petalled with" (covered with short strips of) moleskin as needed.Step 9:
      After the cast is hard, remove the patient from the spica table and wake him/her
      up. Place a smaller diaper over the groin inside the cast to prevent cast soiling
      and a second, larger diaper over the outside of the cast to hold the smaller
      diaper in place. Following cast application, distal neurovascular status is
      assessed. The caretakers are trained in cast care and safe patient transport. The
      fit of the car seat is checked prior to discharge from the emergency room or
      hospital. Follow-up radiographs with the patient in the cast should be obtained
      10 days after cast application. Angulation of <=15 degrees  and shortening of <2
      cm can generally be accepted in patients with a midshaft fracture. Angulation of
      >15 degrees  can often be managed with wedging of the cast in the clinic.
      Excessive shortening may require reapplication of the cast or a change to another
      stabilization method. Single-leg spica treatment of femoral fractures in children
      <=5 years of age has provided reliable outcomes with few complications. Usually,
      the cast can be removed 4 to 6 weeks following application.

PMID- 30233962
TI  - Management of Vancouver Type-B2 and B3 Periprosthetic Femoral Fractures:
      Restoring Femoral Length via Preoperative Planning and Surgical Execution Using a
      Cementless, Tapered, Fluted Stem.
AB  - Introduction: Periprosthetic femoral fractures, which are likely to increase as
      the population ages and total hip arthroplasty becomes more prevalent1, can be
      effectively managed by restoring femoral length via preoperative planning and
      surgical execution using a cementless, tapered, fluted stem. Indications &
      Contraindications:  Step 1 Preoperative Plan: Template the contralateral,
      uninjured side. Step 2 Template the Fractured Side: Identify the ideal COR on the
      injured side and template the femoral stem. Step 3 Establish Depth of Reaming:
      Use stem templates to establish a reference point on the reamer for use
      intraoperatively, and identify the distance from that point to an identifiable
      distal landmark. Results: We report on 14 (12 Vancouver type-B2 and 2 Vancouver
      type-B3) periprosthetic femoral fractures treated with the described method15.
      Pitfalls & Challenges: 

PMID- 30233963
TI  - Three-Dimensional Templating and Use of Standard Instrumentation in Primary
      Anatomic Total Shoulder Arthroplasty.
AB  - Introduction: Three-dimensional (3D) templating of the glenoid in anatomic
      shoulder arthroplasty allows for more accurate planning and more optimal
      positioning of the glenoid component than 2-dimensional computed tomography (2D
      CT) scans through an improved understanding of both the pathologic and the
      premorbid glenoid joint line, version, and inclination in reference to an
      idealized calculated glenoid position. Indications & Contraindications:  Step 1
      Obtain a CT Scan with 3D Reconstruction and Define Glenoid Version and
      Inclination: Obtain a CT scan of the entire scapula and proximal part of the
      humerus with slices of <=1 mm and a 3D reconstruction with subtraction of the
      humeral head, and identify the scapular and glenoid planes to define the
      pathologic version and inclination, which can be done in any commercially
      available software program while following these basic principles (Video 1). Step
      2 Define Premorbid Glenoid Morphology: Carefully evaluate for the presence of the
      native glenoid, noting its version and inclination, and be careful to distinguish
      the true native glenoid from osteophytes (Video 2). Step 3 Place the Virtual
      Implant: Place the virtual glenoid component to restore the premorbid glenoid
      anatomy (Video 3). Step 4 Evaluate the Need for an Augmented Glenoid Component
      Bone Graft or Eccentric Reaming: In the presence of bone loss from posterior
      glenoid wear, assess the need for an augmented glenoid component, bone graft, or
      eccentric reaming to achieve adequate backside seating (Video 4). Step 5 Note the
      Center Pin Position and Trajectory: Once the glenoid component has been
      templated, note the starting location and trajectory of the center pin used for
      cannulated glenoid reaming and bone preparation (Video 5). Step 6 Remove
      Remaining Cartilage and Soft Tissue from the Glenoid Surface: Intraoperatively,
      remove remaining labrum and any remaining cartilage or soft tissue, and expose
      the glenoid periphery to clearly define the osseous anatomy, including the base
      of the coracoid, such that it mirrors what the 3D CT scan and preoperative plan
      display (Video 6). Step 7 Place the Center Pin According to the Preoperative
      Plan: Place the center pin for glenoid preparation in the previously templated
      location and trajectory to emulate the surgical plan defined in the software
      (Video 7). Results: We performed a prospective, randomized controlled trial of
      positioning of the glenoid component in anatomic TSA using preoperative planning
      with 3D CT scans and standard instrumentation compared with using 3D CT
      preoperative planning with patient-specific instrumentation29. Pitfalls &
      Challenges: 

PMID- 30233964
TI  - The Use of Supramalleolar Osteotomies in Posttraumatic Deformity and Arthritis of
      the Ankle.
AB  - Osteoarthritis of the ankle is a debilitating musculoskeletal disease that
      affects approximately 1% of adults worldwide. The most common etiology of ankle
      osteoarthritis is trauma. In general, patients with ankle osteoarthritis are 12
      to 15 years younger than patients with hip or knee osteoarthritis. More than 50%
      of all patients with ankle osteoarthritis exhibit a substantial concomitant
      hindfoot deformity on the supramalleolar and/or inframalleolar level. Different
      treatment options for ankle osteoarthritis, including joint-preserving and non
      joint-preserving surgical procedures, have been described in the current
      literature. Supramalleolar osteotomy is a joint-preserving option that can be
      considered in patients who have asymmetric ankle osteoarthritis, a partially
      preserved ankle joint, and a concomitant supramalleolar deformity. The primary
      goal of the supramalleolar osteotomy is to realign the hindfoot and,
      specifically, the spatial relationship between the talus and the tibia in order
      to restore normal ankle biomechanics and normalize load distribution within the
      ankle joint. Different surgical techniques of supramalleolar osteotomy that are
      based on the underlying deformity, e.g., varus versus valgus, are described. The
      major steps of the procedure, which are demonstrated in this video article,
      include (1) exposure of the distal end of the tibia, (2) determination of the
      osteotomy site, (3) performance of the supramalleolar osteotomy, (4) mobilization
      of the osteotomized distal end of the tibia, (5) internal fixation of the
      osteotomy site, (6) additional balancing, and (7) step-by-step wound closure. In
      some instances, additional procedures are required to balance the ankle joint,
      e.g., inframalleolar osteotomies, arthrodeses, ligament reconstructions, and
      tendon transfers. The postoperative rehabilitation requires non-weight-bearing
      activity for 6 to 8 weeks postoperatively. Intraoperative, perioperative, and
      postoperative complications can occur and are discussed in this article.

PMID- 30233966
TI  - Posterior Malleolar Open Reduction and Internal Fixation Through a Posterolateral
      Approach for Trimalleolar Fractures.
AB  - : Fixation of the posterior fragment in trimalleolar fractures remains a matter
      of debate. Recent studies have shown that a persistent step-off in the tibiotalar
      joint is the most important factor in the development of osteoarthritis and
      therefore the functional outcome. The disadvantages of the regularly performed
      indirect reduction by ligamentotaxis or percutaneous reduction followed by
      percutaneous screw fixation of the posterior fragment in an anterior-to-posterior
      direction are that an anatomical reduction is more difficult to achieve because
      of the interposition of soft tissue or loose osseous fragments, it is hard to
      assess reduction satisfactorily using an image intensifier, and fixation of small
      or comminuted fragments is technically difficult. Therefore, we favor an open,
      anatomical reduction of the posterior malleolar fragment using a posterolateral
      approach. Description: The patient is prone for the operation. A longitudinal
      incision is made between the lateral border of the Achilles tendon and the
      posteromedial border of the fibula. The posterior aspect of the fibula is easily
      reached through the interval just lateral to the peroneal muscle. After
      debridement of the fracture, it can be reduced and is fixed with either (1) a
      buttress plate or (2) lag screw(s) with a neutralizing plate. The belly of the
      flexor hallucis longus is bluntly dissected off of the interosseous membrane and
      the lateral side of the tibia through the interval medial to the peroneal muscle.
      Retracting the muscle belly medially allows the posterior aspect of the tibia to
      be seen. The periosteum is incised to expose the posterior malleolar fracture.
      Loose fragments can be removed by levering the posterior fragment distally.
      Reduction is performed and is held temporarily by Kirschner wires. Fixation is
      undertaken using either lag screws or a slightly prebent 3-hole buttress plate.
      Placement of a lag screw through the most distal hole of the plate can help to
      close any possible gaps. Slight internal rotation of the lower leg allows the
      medial malleolus to be approached and fixed. Alternatives: Percutaneous anterior
      to-posterior screw fixation is an alternative, but it frequently leads to a
      nonanatomical reduction of the fragment. Rationale: This technique provides an
      adequate view of the fracture, an anatomical reduction in most cases, and sound
      fixation of the posterior malleolar fragment. Other advantages are that small
      fragments are easier to fix and small intra-articular fragments can be removed
      from the site of the fracture.

PMID- 30233965
TI  - Virtual Planning and Allograft Preparation Guided by Navigation for
      Reconstructive Oncologic Surgery: A Technical Report.
AB  - Introduction: Advanced virtual simulators can be used to accurately detect the
      best allograft according to size and shape. Indications & Contraindications: 
      Step 1 Acquisition of Medical Images: Obtain a multislice CT scan and a magnetic
      resonance imaging (MRI) scan preoperatively for each patient; however, if the
      time between the scans and the surgery is >1 month, consider repeating the MRI
      because the size of the tumor may have changed during that time. Step 2 Select an
      Allograft Using Virtual Imaging to Optimize Size Matching: Load DICOM images into
      a virtual simulation station (Windows 7 Service Pack 1, 64 bit, Intel Core i5/i7
      or equivalent) and use mediCAS planning software ( medicas3d.com ) or equivalent
      (Materialise Mimics or Amira software [FEI]) for image segmentation and virtual
      simulation with STL (stereolithography) files. Step 3 Plan and Outline the Tumor
      Margins on the Preoperative Imaging: Determine and outline the tumor margin on
      manually fused CT and MRI studies using the registration tool of the mediCAS
      planning software or equivalent (Materialise Mimics software.). Step 4 Plan and
      Outline the Same Osteotomies on the Allograft: Determine and outline the
      osteotomies between host and donor using the registration tool of the mediCAS
      planning software or equivalent (Materialise Mimics software.). Step 5 Assess the
      Patient and Allograft in a Virtual Scenario: Be sure to consider the
      disintegration of bone tissue that occurs during the osteotomy and corresponds to
      the thickness of the blade (approximately 1.5 mm). Step 6 Navigation Settings: A
      tool of the mediCAS planning software allows the virtual preoperative planning
      (STL files) to be transferred to the surgical navigation format, DICOM files.
      Step 7 Patient and Allograft Intraoperative Navigation: The tumor and allograft
      are resected using the navigated guidelines, which were previously planned with
      the virtual platform. Results: The 3D virtual preoperative planning and surgical
      navigation software are tools designed to increase the accuracy of bone tumor
      resection and allograft reconstruction3. Pitfalls & Challenges: 

PMID- 30233967
TI  - Distal Biceps Tendon Anatomic Repair.
AB  - Distal biceps injuries, which usually occur in active middle-aged men, can result
      in chronic pain and loss of supination and flexion strength3,4. Surgical repair
      of a ruptured distal biceps tendon can reliably decrease pain and improve
      strength compared with nonoperative management3,4. However, even following
      successful healing and rehabilitation of a surgically repaired biceps tendon,
      full supination strength is rarely restored5-7. The expected outcome following
      distal biceps repair using a traditional anterior approach is a measurable loss
      of rotational strength, especially from neutral to supinated positions5,7. This
      deficit can lead to difficulty with occupational and recreational activities5,8.
      The center of an uninjured biceps tendon inserts into the radial tuberosity 6.7
      mm anterior to its apex9,10. This posterior location forces the biceps tendon to
      wrap around the radial protuberance during pronation, thus utilizing the
      protuberance as a mechanical cam during forceful forearm supination10,11. The
      distal biceps tendon comprises a medial short head and lateral long head; the 2
      heads are continuations of the proximal muscles2,20,21. The short head inserts
      distal to the long head on their radial attachment site2,20,21. Performing a
      distal biceps repair via an anterior approach typically places the center of the
      reattachment site 12.9 mm anterior to its apex or approximately 6 mm anterior to
      an uninjured control tendon9. This shifts the repair site from its anatomic
      location (posterior to the radial protuberance) to a new nonanatomic location (on
      top of the protuberance). This anterior reattachment location decreases the cam
      effect of the radial protuberance, resulting in an average supination loss of 10%
      in neutral rotation and 33% in 60 degrees  of supination7,10. A posterior
      approach to the radial tuberosity using 2 separate intramedullary buttons for the
      short and long heads reliably positions the distal biceps insertion at its
      anatomic footprint, which is posterior to the radial protuberance9,10,11. This
      technique has been named the distal biceps tendon anatomic repair. Not only does
      it restore the normal supination cam effect of the radial protuberance, but it
      also provides superior initial fixation strength, with load to failure strength
      similar to the native tendon1. The distal biceps anatomic repair can be divided
      into the following 9 key steps: Step 1: Preoperative planning; Step 2:
      Positioning; Step 3: Identifying and retrieving the tendon; Step 4: Preparing the
      2 heads of the tendon; Step 5: Posterior exposure of tendon footprint; Step 6:
      Drilling the short and long-head drill holes; Step 7: Passage of the tendon; Step
      8: Unicortical button fixation; Step 9: Alternative fixation: cortical trough;
      and Step 10: Postoperative management.

PMID- 30233968
TI  - Interlocking Nail Fixation for the Treatment of Displaced Intra-Articular
      Calcaneal Fractures.
AB  - Introduction: Less invasive restoration of joint congruity and calcaneal shape in
      displaced intra-articular calcaneal fractures via a sinus tarsi approach followed
      by percutaneous internal fixation with an interlocking nail results in a low rate
      of soft-tissue complications and good short-term outcomes1 (Video 1). Indications
      & Contraindications:  Step 1 Patient Placement: Place the patient in the lateral
      decubitus position, supporting the involved extremity with a soft radiolucent
      pillow, flex the contralateral knee, check with fluoroscopy before draping, and
      obtain lateral radiographs. Step 2 Incision: Use a sinus tarsi approach for
      control of the articular reduction. Step 3 Percutaneous Manipulation of the Main
      Fragments: Percutaneously manipulate the main fragments to facilitate reduction
      of the main tuberosity fragment toward the sustentacular fragment and subsequent
      joint reduction. Step 4 Joint Reduction with Direct Manipulation of the Main
      Fragments through the Sinus Tarsi Approach: Reduce the joint with direct
      manipulation of the main fragments through the sinus tarsi approach. Step 5 Joint
      Fixation with Screws: Check the congruency of the posterior subtalar joint facet,
      stabilize the posterior facet with 2 screws, reduce the tuberosity against the
      joint block and anterior process, and temporarily fix with Kirschner wires. Step
      6 Introduction of the Intramedullary Nail: Make a 10-mm vertical incision below
      the attachment of the Achilles tendon, direct the guidewire toward the center of
      the calcaneocuboid joint, place the guidewire centrally within the calcaneal
      body, ream over the guidewire, and introduce the intramedullary nail with the
      attached aiming device. Step 7 Locking of the Nail: Use the aiming device to
      position the proximal Kirschner wire into the sustentacular fragment, place the
      nail so that it hits the sustentaculum tali properly, insert a second Kirschner
      wire through the other hole of the guiding arm, exchange the wires after drilling
      for locking screws, apply an end cap to extend the length of nail, if needed, and
      then verify proper reduction and implant position fluoroscopically. Step 8
      Postoperative Management: Manage the patient with continuous passive motion and
      active range-of-motion exercises of the ankle beginning on postoperative day 2
      and allow partial weight-bearing of 20 kg for 6 to 10 weeks. Results: Recently,
      we reported on 103 patients with 106 intra-articular calcaneal fractures treated
      with the C-Nail by 4 senior surgeons from February 2011 to October 20131.
      Pitfalls & Challenges: 

PMID- 30233969
TI  - Recommendations to Reduce Risk of Nerve Injury During Bernese Periacetabular
      Osteotomy (PAO).
AB  - The Bernese periacetabular osteotomy (PAO) is a widely used procedure to reorient
      a dysplastic acetabulum resulting from developmental dysplasia of the hip,
      retroversion, protrusio, or some deformities with a traumatic etiology.
      Throughout the execution, the lateral femoral cutaneous nerve (LFCN) as well as
      the obturator, femoral, and sciatic nerves can be injured. Injury to 1 of the 3
      major nerves is a devastating event for the patient followed by an ill-defined
      period of hope for nerve recovery and fear of lifelong disability. Surgical
      experience is an essential factor in reducing the prevalence of nerve injury,
      whereas proof of the value of intraoperative fluoroscopy and nerve monitoring
      still must be established. Although it is known that, for example, the ischial
      cuts of the complex osteotomy place the sciatic nerve at risk, the action causing
      the nerve injury is rarely clear in the individual situation. The literature has
      been mostly limited to reports of incidence and offers little analytic
      information. Through the use of cadaveric dissections, we visualized the possible
      impacts of the different steps of the procedure on the nerves in their anatomic
      vicinity, and the present report demonstrates how nerves can be protected with
      retractor positioning and how lower-limb positioning can lead to nerve
      relaxation, an important means to avoid mechanical injury. While the frequent
      injuries of the LFCN are exclusively related to the approach, sciatic nerve
      injuries are mainly the result of the ischial osteotomy steps and femoral nerve
      injuries are seen nearly exclusively with the correction of the acetabular
      fragment. The authors implemented the demonstrated measures for 9 years, during
      which approximately 800 periacetabular osteotomies resulted in a total of 2
      femoral and 2 sciatic nerve lesions-or a nerve injury rate of 0.5%. The nerves
      injuries resolved within 6 to 9 months in 3 hips, and 1 patient had a definitive
      foot drop requiring a splint at the time of writing.

PMID- 30233970
TI  - Open Treatment of Radial Head Fractures.
AB  - Radial head fractures may commonly be treated by (1) open reduction and internal
      fixation (ORIF), (2) radial head excision, or (3) radial head replacement. If
      there is no associated elbow instability with lateral ulnar collateral ligament
      (LUCL) injury, the preferred approach is via a split in the extensor digitorum
      communis (EDC) origin. This provides a wide exposure but limits the risk of
      injury to the LUCL and associated instability. The radial head is fixed, excised,
      or replaced. Open treatment of radial head fractures begins with the following
      steps: (1) a laterally based incision is centered over the radiocapitellar joint,
      (2) the EDC is split at the midline of the radial head and elevated off the bone
      anteriorly and superiorly, and dissection proceeds distally, splitting the
      extensor origin along its fibers, and (3) the capsule is opened and the radial
      head fracture, identified. For ORIF, provisional fixation is then obtained with
      Kirschner wires and small bone reduction clamps. Headless low-profile screws are
      preferred if possible. If a plate is used, the dissection proceeds distally and
      the posterior interosseous nerve may need to be identified and protected.
      Definitive fixation is applied in the safe zone for implant placement (i.e., a
      right angle based laterally when the forearm is in a neutral position). For
      excision of the radial head as definitive treatment or for radial head
      replacement, the fragments are removed and an oscillating saw is used to remove
      additional radial neck or other fragments. When radial head excision is the
      definitive treatment, the radial neck is planed to a smooth contour that allows
      for placement of the prosthesis or for smooth motion without impingement at the
      proximal radioulnar joint. An indication for radial head replacement is suspicion
      of an Essex-Lopresti-type injury or demonstration of longitudinal instability of
      the forearm with excessive motion when a "push-pull" test is performed under
      fluoroscopy of the wrist while traction is applied to the radial neck. The final
      step of open treatment of radial head fractures, before the wound is closed in
      layers, consists of assessment of the range of motion and use of fluoroscopy to
      confirm appropriate fixation, resection, or prosthetic position. Outcomes
      following radial head fixation, resection, or arthroplasty for isolated radial
      head fractures are generally favorable. Loss of motion is particularly
      problematic in the pronation-supination arc in the setting of plate fixation, and
      patients are generally counseled that implant removal is often necessary. Loss of
      motion in the flexion-extension arc, particularly loss of terminal extension, may
      be noted. Resection of the radial head results in radiographic evidence of
      degenerative changes along the ulnohumeral joint, but this may be well tolerated
      as symptoms develop slowly, particularly in older patients. Radial head
      replacement results in changes in the capitellum over time, but these are usually
      asymptomatic.

PMID- 30233971
TI  - Rotational Acetabular Osteotomy.
AB  - : Hip dysplasia is a common cause of secondary osteoarthritis. To prevent the
      early onset of secondary osteoarthritis, rotational acetabular osteotomy has been
      proposed1. Description: The approach combines the anterior iliofemoral and
      posterior approaches through a single skin incision. The pubic bone is cut
      independently, and the ilium and ischium are cut in continuity. The rotation of
      the acetabulum provides a more horizontal weight-bearing area and, at the same
      time, returns the superiorly subluxated femoral head to a more normal position.
      Alternatives: The Ganz periacetabular osteotomy involves the same concept as a
      rotational acetabular osteotomy with a different surgical approach. The rate of
      major complications, such as intra-articular osteotomy, nerve palsy, loss of
      fixation, malreduction, and symptomatic heterotopic ossification, is lower in
      rotational acetabular osteotomy (0% to 18%)2 than in periacetabular osteotomy (6%
      to 37%)3. Because of a wide surgical exposure, osteotomy can be performed under
      direct vision in rotational acetabular osteotomy. Rationale: Rotational
      acetabular osteotomy for osteoarthritis secondary to hip dysplasia can alter the
      position of the acetabulum en bloc and cover the femoral head with cartilage. For
      the unstable hip with dysplasia, the surgical procedure is needed for the
      prevention of osteoarthritis.

PMID- 30233972
TI  - Bony Increased Offset-Reversed Shoulder Arthroplasty (BIO-RSA).
AB  - Introduction: Bony increased offset-reversed shoulder arthroplasty (BIO-RSA) is
      an effective and safe means of achieving lateralization of the prosthetic center
      of rotation in reverse shoulder arthroplasty. Indications & Contraindications: 
      Step 1 Preoperative Planning: Confirm the indication for surgery and obtain
      radiographs and 3-dimensional (3D) imaging (computed tomography [CT] or magnetic
      resonance imaging [MRI] scans) to confirm the suitability for a BIO-RSA. Step 2
      Patient Positioning and Surgical Approach Video 1: With the patient in the beach
      chair position, approach the shoulder via a standard deltopectoral approach. Step
      3 Harvesting of Humeral Graft and Initial Humeral Preparation: Dislocate the
      humeral head anteriorly and use the instrumentation to harvest a 29-mm fully
      cancellous graft of desired thickness from the humeral head. Step 4 Glenoid
      Exposure Preparation and Prosthetic Implantation: Carefully and meticulously
      expose and prepare the glenoid for prosthetic implantation. Step 5 Humeral
      Preparation and Prosthetic Implantation: Prepare and implant the humeral
      prosthesis as per the standard surgical technique described for implantation of
      the Aequalis Reversed prosthesis10. Step 6 Postoperative Management:
      Postoperative management is the same as that for a nonlateralized reverse
      prosthesis, with no alteration in rehabilitation required. Results: In our
      original series of 42 patients with a minimum follow-up of 2 years (mean, 28
      months), the glenoid bone graft incorporated completely in 41 patients and
      partially in 1 patient (Fig. 5)6. Pitfalls & Challenges: 

PMID- 30233973
TI  - Open Treatment of Olecranon Fractures with Plate Fixation.
AB  - Fractures of the olecranon are sometimes difficult to treat. The steps for
      operative plate fixation of olecranon fractures consist of (1) a dorsal incision,
      (2) exposure using full-thickness flaps, (3) removal of hematoma from the
      fracture site, (4) fracture reduction, (5) provisional fixation, (6) plate
      application, (7) proximal fixation, (8) distal fixation, and (9) layered wound
      closure. Although this is generally a straightforward procedure, several specific
      steps may make fixation easier and improve outcomes. Outcomes following olecranon
      fracture fixation are generally good. Patients should expect some loss of
      terminal extension and a potential for symptoms related to implant prominence,
      especially in slender patients. Ulnar nerve symptoms are unusual but possible.

PMID- 30233974
TI  - Combined ACL and Anterolateral Ligament Reconstruction.
AB  - Background: Clinical results of combined anterior cruciate ligament (ACL) and
      anterolateral ligament (ALL) reconstruction have demonstrated a significant
      reduction in ACL graft rupture rates and improved rates of return to sports
      compared with isolated ACL reconstruction1. This finding is supported by
      laboratory studies that have demonstrated that combined ACL reconstruction and
      lateral extra-articular tenodesis procedures protect the ACL graft by load
      sharing with it and by more reliably restoring normal knee kinematics compared
      with isolated ACL reconstruction. Description: The ACL graft is formed from a
      tripled semitendinosus tendon and a single strand of gracilis tendon. The femoral
      tunnel is drilled to provide an anatomic location intra-articularly and to exit
      the femur just posterior and proximal to the lateral epicondyle. The additional
      length of gracilis therefore exits the femoral tunnel at the anatomic origin of
      the ALL and is then routed (under the iliotibial band [ITB]) through a tibial
      tunnel, and back to the femoral origin, to reconstruct the ALL. Alternatives:
      Many different types of nonanatomic lateral extra-articular tenodesis procedures
      have been reported. The most frequently performed were the Lemaire and MacIntosh
      procedures; however, these, and others, were widely abandoned after poor results
      were reported in the 1980s. Rationale: ALL reconstruction differs from other
      lateral extra-articular tenodesis-type procedures because the procedure is
      anatomically based and can be percutaneously performed. Nonanatomic procedures
      (typically with a strand of ITB passed under the lateral collateral ligament
      [LCL]) have been reported to be associated with overconstraint, early arthritis,
      and an increased risk of infection2-5. In contrast, ALL reconstruction has been
      shown to restore normal knee kinematics and to avoid overconstraint when
      correctly fixed in full extension and neutral rotation6. The main concern with
      any type of lateral extra-articular tenodesis is based on historical reports of
      poor outcomes2,3. However, a recent study has demonstrated that combined ACL and
      ALL reconstruction is associated with a reoperation rate that is comparable with
      the rate seen after isolated ACL reconstruction, and it has a very low rate of
      complications7. This makes a compelling argument for anatomic ALL and ACL
      reconstruction being the procedure of choice when considering an extra-articular
      procedure. This is further supported by the fact that, even though previous
      studies have demonstrated a trend toward reduced ACL graft rupture with
      nonanatomic lateral extra-articular tenodesis procedures, they have not shown a
      significant improvement in outcomes8. Combined ACL and ALL reconstruction is
      currently the only type of lateral extra-articular procedure that has been
      demonstrated to significantly reduce the risk of ACL graft rupture and improve
      the rate of return to sports1.

PMID- 30233975
TI  - Allograft-Prosthetic Composite Reconstruction for Massive Proximal Humeral Bone
      Loss in Reverse Shoulder Arthroplasty.
AB  - Background: Allograft-prosthetic composite (APC) reconstruction of the humerus
      represents an appealing surgical technique when implantation of a reverse
      prosthesis is considered in the setting of substantial proximal humeral bone
      loss1-4. Humeral APCs have been successfully performed in the past with a non
      reverse shoulder prosthesis4,5. Reconstruction of the proximal part of the
      humerus with an allograft provides adequate support and fixation for the humeral
      component, allows restoration of length and lateral offset, and provides an
      opportunity for soft-tissue reattachment when needed. On the basis of the
      available peer-reviewed data, healing at the allograft-host junction is reliable,
      and complication rates, including instability, are relatively low3,6.
      Description: Once the glenoid reverse component has been implanted, a proximal
      humeral allograft is prepared to receive the humeral component of a reverse
      arthroplasty. The allograft is procured by our institutional bone and tissue
      bank, purchased from a number of vendors. The graft is selected after review of
      the description and radiographs provided by the vendor. The priority is to obtain
      a graft with sufficient length and soft tissues attached. If possible, the graft
      selected should have a diameter close to the diameter of the humerus of the
      recipient. The desired allograft length is selected on the basis of preoperative
      planning and intraoperative measurements, and the distal portion of the allograft
      is resected accordingly. Depending on the length of the defect, host bone
      quality, and surgeon preferences, the humeral component may or may not bypass the
      host-graft junction. The stem bypasses the host-graft junction for shorter APCs,
      as well as when the bone quality of the native humerus is compromised. Cemented
      fixation into the graft is universally used. Compression plating is used for
      graft-to-host fixation, supplemented by implantation of the stem across the
      junction in selected cases. Care is taken during the freehand cut to obtain
      optimal contact and compression. Once the ideal humeral bearing thickness has
      been selected, the polyethylene bearing is implanted and the joint relocated. If
      the posterior cuff can be repaired to cuff allograft, sutures are placed prior to
      relocation and are tied after relocation. Other musculotendinous units, such as
      the deltoid or pectoralis major, are repaired to the allograft if needed.
      Alternatives: Implantation of a reverse prosthesis with a proximal humeral metal
      body (a so-called tumor prosthesis) is the main alternative to proximal humeral
      APC reconstruction. In patients with shorter defects, adequate soft-tissue
      tension may be obtained by implanting a glenosphere with a large inferior
      eccentricity and cementing the humeral component in a more proximal position than
      is usually performed. Alternatively, when implantation of the glenoid component
      of a reverse prosthesis is not possible, a hemiarthroplasty-APC construct may be
      performed1,4,5,7-10, adding a synthetic sleeve such as an aortic Dacron graft to
      enhance soft-tissue stability if needed. Rationale: When reverse arthroplasty is
      performed in the setting of substantial humeral bone loss, the humeral component
      may be poorly supported and at risk for loosening. In addition, the absence of
      proximal humeral bone stock may lead to shortening and/or loss of lateral offset.
      Finally, the posterosuperior cuff, subscapularis, deltoid, and pectoralis tendons
      may remain detached. The potential consequences of humeral bone loss in the
      setting of reverse arthroplasty include humeral loosening, dislocation, and poor
      active motion (particularly poor active elevation). Allograft reconstruction of
      the proximal part of the humerus provides an opportunity for better support of
      the component, restoration of humeral length and lateral offset, and attachment
      sites for the musculotendinous structures around the shoulder, if needed.

PMID- 30233976
TI  - Triceps Tendon Repair.
AB  - Although triceps tendon ruptures can result from a traumatic incident, chronic
      overuse causing degenerative changes to the insertion and leading to a complete
      or partial rupture is more common. In our practice, we have found that anabolic
      steroid abuse by weightlifters is the most common predisposing factor. The
      initial diagnosis is often missed. A thorough clinical examination is imperative
      to avoid missing a partial or complete rupture. Ultrasound or magnetic resonance
      imaging can confirm the diagnosis. Early diagnosis increases the chance of a
      direct repair. Operative treatment with direct repair is usually indicated for
      full-thickness or large partial-thickness tears. Direct repair may be possible
      for selected chronic tears. Triceps tendon repair is performed with the following
      steps.Step 1: The patient is placed in lateral decubitus.Step 2: The stump is
      debrided, and retraction of the tendon is evaluated.Step 3: Two crossed bone
      tunnels are drilled, and an anchor is placed centrally in the olecranon.Step 4:
      The elbow is extended, and the tendon is reduced and sutured centrally to the
      anchor and medially and laterally with use of the sutures from the bone
      tunnels.Step 5: The elbow is flexed to evaluate tension. If gapping occurs, the
      repair should be reinforced with extra sutures. Tension-free range of motion will
      guide postoperative rehabilitation.Step 6: A posterior splint is applied in the
      operating room with the elbow extended.Step 7: A dynamic brace is applied on the
      first postoperative day. Extension is free but flexion is blocked at the tension
      free range; 30 degrees  of extra flexion is permitted every 2 weeks. Full flexion
      is always allowed after 6 weeks. Strengthening starts at 3 months. Pitfalls of
      the procedure include difficulty in differentiating between tendon and scar in
      subacute and chronic ruptures. It may not be possible to directly repair the
      triceps back to bone, and a graft may be needed to reconstruct the tendon. It is
      important to know where the ulnar nerve is and to release it if needed. It is
      important not to debride past the cortical surface of the olecranon if an anchor
      is used because, if this is done, fixation may be insufficient. The anchor should
      be predrilled as the cortical bone of the tip of the olecranon is very dense.
      Reruptures occur in up to 21% of cases. A functional range of motion is usually
      achieved with an average loss of extension of 10 degrees  and average flexion to
      136 degrees . At 1 year, one can expect a peak strength of approximately 80% of
      that on the uninjured side and endurance strength of 99%1.

PMID- 30233977
TI  - Isolated Medial Patellofemoral Ligament Reconstruction with Semitendinosus Tendon
      Allograft.
AB  - Background: Medial patellofemoral ligament (MPFL) reconstruction is recommended
      to surgically stabilize the patella against excessive lateral patellar
      translation. It is currently the cornerstone of treatment for recurrent lateral
      patellar instability. The MPFL is often disrupted during acute patellar
      dislocations but may also be attenuated in the setting of recurrent lateral
      instability. Numerous techniques have been developed with the primary goal of
      restoring the static function of the MPFL in resisting lateral translation of the
      patella during early flexion of the knee. There are now numerous options for the
      surgical technique, fixation devices, and graft choice, with equal clinical
      results as long as key surgical principles are maintained1. This article provides
      a step-by-step description of our preferred technique as well as offering
      technical pearls and a review of patient outcomes. Description: The MPFL is
      reconstructed anatomically using a hamstring allograft or autograft with an ideal
      width of 4 to 5 mm. The graft is secured to the femur with an interference screw
      at its anatomic insertion point, which can be defined by radiographic or anatomic
      landmarks, is passed through the soft tissues between the capsule and the medial
      retinaculum/vastus medialis oblique muscles, and is secured to the superomedial
      patellar border. Alternatives: Nonoperative treatment of lateral patellar
      dislocations is associated with recurrent dislocation rates of 35% to 50%;
      surgical treatment for recurrent dislocations has afforded improved patient
      outcomes2,3. In general, there are 3 surgical options to restore the function of
      the MPFL. Historically, acute repair was thought to offer the MFPL a chance to
      "heal" and resume its function; however, the literature has failed to support
      this as a reliable option in the setting of lateral patellar instability4.
      Similarly, delayed tightening or imbrication of the MPFL in the setting of
      chronic laxity has not demonstrated worthwhile clinical results5. MPFL
      reconstruction with a graft, as described here, has provided the most consistent
      outcomes. Rationale: Isolated reconstruction of the MPFL is indicated for
      patients with a history consistent with recurrent lateral patellar instability
      and a physical examination demonstrating excessive lateral patellar translation.
      Patients with high-grade trochlear dysplasia and patella alta may be better
      treated with concomitant osseous procedures such as trochleoplasty or tibial
      tubercle osteotomy.

PMID- 30233978
TI  - A Posterior Approach to Open Reduction and Internal Fixation of Displaced
      Posterior Cruciate Ligament Tibial Osseous Avulsions.
AB  - Background: The true prevalence of displaced tibial-sided avulsion injuries of
      the posterior cruciate ligament (PCL; Video 1) is unknown, and the majority of
      data regarding management has been published in areas other than the Western
      world, such as China and India (perhaps due to the higher prevalence of two
      wheeler motorcycle accidents in these areas). Despite the rarity of data, a
      better understanding of the approach, fixation techniques, and outcomes is
      necessary to provide quality patient care. These injuries generally require
      surgical intervention as nonoperative management leads to complications
      specifically, knee arthrofibrosis1,2. There is no consensus regarding the optimal
      surgical approach for these injuries. A recent systematic review demonstrated
      that both open and arthroscopic surgical treatment provide satisfactory
      complication rates and outcomes in the majority of cases3. However, the
      arthroscopic approach can be performed by only a highly skilled arthroscopist;
      thus, in this article we focus on the open approach to reach a broader audience
      of capable surgeons. Description: The principal steps for open reduction and
      internal fixation of the tibial avulsion fracture include the following:Place the
      patient in a prone position and utilize a curvilinear L-shaped incision with the
      longitudinal portion over the medial head of the gastrocnemius muscle and the
      transverse portion starting distal to the joint line and extending laterally past
      the midline.Develop the interval between the semimembranosus and medial
      gastrocnemius muscles, as originally described by Burks and Schaffer4. Lateral
      retraction of the gastrocnemius muscle exposes the posterior aspect of the
      capsule, allowing for a vertical capsular incision to adequately visualize the
      avulsed osseous fragment.Prepare the osseous bed and remove hematoma and/or
      debris.Reduce the avulsed fragment and obtain provisional fixation with Kirschner
      wires.Confirm reduction under fluoroscopy with emphasis on sagittal plane
      alignment.Obtain definitive fixation with the method dictated by the fracture
      orientation. Options include screw(s) with or without a washer, sutures,
      Kirschner wires, staples, and toothed plates2,5-7. Alternatives: An arthroscopic
      approach can be performed, with results that are similar to those of an open
      procedure, but considerable expertise is required to perform this procedure
      arthroscopically. Nonsurgical management is not recommended as it frequently
      leads to loss of knee motion. Rationale: The exact operative indications for PCL
      injuries remain in question, but we believe that displaced tibial avulsion
      injuries at the PCL attachment always require operative treatment.

PMID- 30233979
TI  - Landmark Technique for a Wrist Block.
AB  - Effective anesthesia of the hand and wrist has many uses inside and outside the
      operating room. In the emergency department or fracture clinic, a wrist block may
      be used for closed reductions of dislocations and fractures or for effective
      inspection and treatment of wounds. In the operating room, surgery may be carried
      out under a wrist block alone or a wrist block may be used as an adjunct to
      general anesthesia as the block is an opiate-sparing option to facilitate
      outpatient surgery and to provide many hours of postoperative analgesia,
      particularly if administered prior to the commencement of surgery. The landmark
      technique for distal peripheral nerve blocks at the wrist is a well-recognized
      method and is described for the median nerve, ulnar nerve, superficial branch of
      the radial nerve, and dorsal branch of the ulnar nerve at the wrist. To make this
      technique more effective for carpal surgery, blocks of the posterior interosseous
      and anterior interosseous nerves are added.Step 1: The patient is counseled about
      the procedure and the expected outcomes.Step 2: Drug allergies are checked.Step
      3: The maximum safe dose of the chosen local anesthetic agent is calculated using
      the weight of the patient.Step 4: The drug ampules are checked for the name and
      concentration of the drug as well as the expiration date.Step 5: The drug is
      drawn up into a 10-mL syringe, and a needle is fitted for injection.Step 6: For
      each of the 6 nerves to be blocked, the anatomical landmarks are identified along
      with surrounding structures at risk.Step 7: The skin is prepared with an
      antiseptic agent.Step 8: The nerve block injections are administered using the
      techniques in the accompanying video, while checking that there are no signs of
      intraneural or intravascular injection. The landmark technique for wrist block is
      an effective method in the situations described above. However, there are
      occasional failures to provide sufficient analgesia as with all peripheral nerve
      block techniques. There is a possibility of intraneural injection, which must be
      avoided. There is also a risk of direct nerve fascicular injury with the needle,
      which therefore requires a thoughtful technique. There is little if any motor
      block, which makes the technique particularly suitable when intraoperative active
      motion is required or when physiotherapy is started directly postoperatively. The
      technique is very rapid to administer, and it does not require any equipment
      other than a syringe and needle, making it very inexpensive and suitable for
      austere environments.

PMID- 30233981
TI  - Tibial Bone Transport Over an Intramedullary Nail Using Cable and Pulleys.
AB  - Background: Massive bone defects (>8 cm) will not unite without an additional
      intervention. They require a predictable, durable, and efficient method to regrow
      bone. The Ilizarov method of tension stress, or distraction osteogenesis, first
      involves a low-energy osteotomy1-5. The bone segments are then pulled apart, most
      often using an external device at a specific rate and rhythm (distraction phase),
      after which the newly formed bone (the regenerate) requires time for
      consolidation. The consolidation phase is variable and usually requires a
      substantially greater amount of time before the external device can be removed.
      Our technique of tibial bone transport over an intramedullary nail using cable
      and pulleys combines internal and external fixation, allowing the external
      fixator to be removed at the end of the distraction phase. This increases the
      efficiency of limb reconstruction and decreases the external-fixator-associated
      complications. Description: The procedure begins with thorough debridement,
      orthogonal tibial cuts, osteotomy, and insertion of a custom intramedullary nail.
      A 1.8-mm steel cable is wrapped around the anterior cortex of the distal end of
      the transport segment and exits the skin distal to the docking site. Two standard
      rings are applied at the proximal and distal aspects of the leg, and 2 pulleys
      are attached to the ring at the ankle. The steel cable is then attached to
      slotted threaded rods that connect to the compression distraction rods that will
      pull the cable up and the bone segment down. Two Ilizarov "clickers" that rotate
      0.25 mm with each "click" are the motor of the system. Once the bone transport
      system is removed, a custom interlocking bolt is placed to capture the transport
      segment. This prevents recoil of the fragment as there is a substantial amount of
      tension in the system. Alternatives: There are no nonsurgical options for
      reconstruction of massive bone loss. The several alternatives for surgical
      reconstruction include the inducible membrane Masquelet technique; circular
      fixation alone with standard Ilizarov bifocal transport, hexapod bifocal
      transport, or trifocal transport; bone transport and then insertion of an
      intramedullary nail (Lengthening and Then Nailing, or LATN); and amputation2-8.
      Rationale: The standard Ilizarov method for posttraumatic bone loss with external
      fixation is a well-established surgical procedure with high union rates. However,
      an external fixator has a high association with pin site infection, and it is
      cumbersome for the patient. In addition, scarring associated with the wires and
      half-pins as they progress down the limb is unsightly and painful. The advantage
      of the cable-pulley system is that the frame is used only in static mode; the
      cable that pulls the bone transport segment remains at the same exit point of the
      skin, thus limiting scarring. In addition, as soon as the distraction phase is
      completed, the external device can be removed. This substantially decreases the
      time that the external fixator needs to be in place.

PMID- 30233980
TI  - Bone Peg Grafting for Capitellar Osteochondritis Dissecans in Adolescent Baseball
      Players.
AB  - Background: Capitellar osteochondritis dissecans (OCD) is a focal injury of the
      articular cartilage involving separation of a segment of cartilage from the
      subchondral bone that is infrequently encountered in the dominant-side elbow of
      adolescent throwing athletes1,2. The literature suggests that patients may
      achieve better short and mid-term results when treated with certain types of
      surgical procedures3,4. Selection of the appropriate surgical method should be
      based on the International Cartilage Repair Society (ICRS) OCD classification
      system5. For lesions involving <=50% of the surface area of the capitellum,
      debridement with microfracture and/or loose body removal have shown excellent
      results. For lesions involving >50% of the surface area of the capitellum and
      classified as ICRS OCD III or IV, autologous osteochondral grafting may be the
      most suitable treatment6-8. Bone peg grafting (BPG) has been shown to be an
      effective treatment option for early-stage capitellar OCD that can preserve the
      local hyaline cartilage9,10. Description: Using direct vision and with
      arthroscopy, the continuity of the capitellar surface and the stability of the
      capitellar lesion were evaluated according to the ICRS OCD classification5. BPG
      was indicated for adolescents with ICRS OCD I or II. The elbow was opened between
      the extensor carpi ulnaris and the anconeus muscle (Kocher interval). Another
      skin incision of 3 cm in length was made at the posterior aspect of the
      metaphysis of the ipsilateral olecranon. Three, 4, or 5 bone pegs of
      approximately 20 mm in length were harvested from the posterior ulnar cortex. A
      Kirschner wire of 3 mm in diameter was used for drilling holes in the lesion, and
      then the bone pegs were inserted with tweezers to a depth of 10 mm. Next, a flat
      surfaced rod was placed on the head of each bone peg to press it to a depth
      slightly lower than the articular cartilage surface. Postoperatively, the elbow
      was immobilized for 3 weeks. Throwing was allowed at 6 months, and a return to
      competitive baseball at preinjury levels was permitted at 8 months after BPG.
      Alternatives: Arthroscopic debridement of the lesion.Arthroscopic bone marrow
      stimulation or microfracture.Fragment fixation using metal implants or
      biodegradable materials.Use of autologous osteochondral graft from the distal
      aspect of the femur or from a rib. Rationale: Our follow-up study after BPG
      revealed that 10 of 11 patients with ICRS OCD I or II capitellar OCD could return
      to their preinjury baseball ability and that 8 of the 11 lesions completely
      healed as seen radiographically11. Radiographic and magnetic resonance imaging
      (MRI) findings showed that BPG could secure the lesion to the osseous floor as a
      physiological scaffold. Fragment fixation with metal implants or biodegradable
      materials carries a risk of damaging cartilage surfaces, and autologous
      osteochondral grafting is too invasive for this early-stage lesion. BPG is
      indicated for ICRS OCD I or II lesions, especially with central positioning
      and/or occupying <75% of the size of the capitellum in the coronal plane11.

PMID- 30233982
TI  - Closed Reduction and Percutaneous Pinning of Pediatric Supracondylar Humeral
      Fractures.
AB  - Supracondylar humeral fractures are the most common elbow fractures in children
      requiring operative intervention. They are classified according to the Gartland
      system as nondisplaced (type I), displaced with hinging and the posterior cortex
      intact (type II), and completely displaced (type III). The standard treatment for
      type-II and III fractures is closed reduction and percutaneous pinning. The
      timing of surgery depends on the severity of the fracture and the presence of any
      neurovascular injury. Preoperative assessment of the neurologic and vascular
      status is imperative, and can be challenging in a young child. The steps of the
      surgical procedure consist of the following.Position the patient supine with the
      affected extremity on a fluoroscopy detector or hand-table.Perform closed
      reduction.Apply longitudinal traction with the elbow in 30 degrees  of
      flexion.Correct medial or lateral translational displacement.Correct varus or
      valgus malalignment.Maintain traction and flex the elbow, placing pressure over
      the olecranon process to correct extension at the fracture site.Assess reduction
      using anteroposterior, oblique, and lateral fluoroscopic views.Place divergent
      pins from the lateral side, using 2 pins for type-II and 3 pins for type-III
      fractures.Assess stability by moving the elbow through a range of motion under
      live fluoroscopy in the lateral projection. If the fracture is determined to be
      unstable with lateral-only pins, proceed with medial pin placement through a mini
      open approach.Cut the pins and bend them outside the skin. Then apply a long-arm
      bivalved cast. The pins are removed between 3 and 4 weeks postoperatively,
      depending on patient age, and range of motion is initiated. Elbow stiffness is
      common for 4 to 6 weeks, but a return to a nearly full range of motion can be
      expected. Resumption of normal activities should be delayed until the fracture is
      fully healed and the range of motion is nearly normal.

PMID- 30233983
TI  - Solitary Trochleoplasty for Treatment of Recurrent Patellar Dislocation.
AB  - Background: Solitary trochleoplasty for recurrent patellar dislocation offers a
      unique benefit in that it addresses the most important factor in patellar
      instability: the trochlear dysplasia. Description: The trochlea is visualized
      through a lateral arthrotomy of the knee joint. An osteochondral layer is peeled
      off with curved chisels and extended into the intercondylar notch. A triangular
      bone block is removed from the subchondral bone to form the new groove. A new
      groove is begun with a chisel and smoothed with a high-speed burr. Also, the
      osteochondral layer is thinned out and fixed back transosseously in the new
      groove with 2 Vicryl (polyglactin) bands. The bone block is used to lengthen the
      lateral condyle by placing it under the osteochondral layer at the proximal
      extension of the lateral femoral condyle with an overlap of 1 cm. Alternatives:
      Nonsurgical alternatives include a knee or patellar brace, taping of the patella,
      and physiotherapy for strengthening of the vastus medialis obliquus of the
      quadriceps muscle. Surgical alternatives include reconstruction of the medial
      patellofemoral ligament; several femoral and tibial osteotomies, such as
      rotational osteotomies of the femur and tibia or medialization of the tibial
      tuberosity; and several soft-tissue interventions, such as medial reefing,
      relocation of the patellar tendon as described by Goldthwait1, and proximal
      realignments according to the method described by Insall et al.2 or Green et
      al.3. Rationale: Most patients with recurrent patellar dislocation have a
      dysplastic trochlea4, which is considered to be the primary reason for a
      recurrence. While interventions such as reconstruction of the medial
      patellofemoral ligament or femoral and tibial osteotomies also provide stability
      of the patella, they do not change the most essential factor of the instability
      the trochlear dysplasia. The trochleoplasty addresses this underlying condition
      and reshapes the trochlea.

PMID- 30233985
TI  - Use of Suture Button in the Treatment of Syndesmosis Injuries.
AB  - A suture button device provides fixation of syndesmosis injuries of the ankle
      with or without concomitant malleolar fracture. The suture button device consists
      of a fiber thread attached between 2 small metal buttons. The buttons are placed
      on the cortical bone on the medial and lateral sides of the ankle, and the fiber
      thread is tightened to stabilize the syndesmosis. The suture button device offers
      stable yet dynamic fixation of the injured syndesmosis. The major steps of the
      procedure are (1) lateral skin incision straight to the bone; (2) open reduction
      and plate fixation of the fibular fracture if one is present; (3) reduction of
      the syndesmosis and temporary stabilization with a pin or clamp; (4) use of an
      appropriate burr to make a hole through 4 cortices at the level of the inferior
      tibiofibular joint, approximately 1.5 cm proximal to the ankle joint line and at
      a 20 degrees  to 30 degrees  lateral-to-anteromedial angle; (5) pulling the
      needle attached to the suture button device through the drill-hole from lateral
      to medial and flipping the small plate on the cortical bone of the medial cortex
      of the medial malleolus; (6) tightening the device by pulling the 2 threads on
      the lateral side with care taken to remove all of the slack from the system; and
      (7) checking placement and fixation with fluoroscopy, cutting the threads, and
      skin closure. Use of a walker boot or cast is decided on the basis of the
      fracture fixation. Partial weight-bearing is allowed for the first 6 weeks, after
      which full weight-bearing is permitted as pain allows. Routine removal of the
      suture button device is not required.

PMID- 30233986
TI  - Olecranon Osteotomy-Facilitated Elbow Release (OFER).
AB  - Background: The olecranon osteotomy-facilitated elbow release (OFER) is a safe
      and effective method for releasing severe posttraumatic elbow contractures. The
      OFER procedure is easier, faster, and relatively less invasive, and appears to
      offer superior outcomes, compared with more traditional techniques. Description:
      An olecranon osteotomy provides a trapdoor through which the surgeon will have
      circumferential access to the joint and will be able to address all intrinsic and
      extrinsic causes of contracture. Access from the posterior to the anterior
      compartment is achieved by detaching the origin of the medial collateral ligament
      (MCL) and hinging the joint from medially to laterally, pivoting around the
      intact lateral collateral ligament. Once the olecranon and MCL are repaired, the
      elbow is stable enough for the patient to participate in intensive rehabilitation
      protocols. Alternatives: The first line of treatment for elbow contracture is
      physical therapy, focusing on range of motion and using modalities such as static
      progressive and dynamic splinting protocols. In some select cases, there is also
      a role for manipulation under anesthesia. When nonoperative methods fail, elbow
      contractures may be treated surgically, using either open or arthroscopic
      techniques. Authors have described open release involving medial, lateral, and
      anterior approaches. The first outcome report of a posterior approach to treat
      elbow contractures has recently been published1. Rationale: An open approach
      usually utilizes 1 or possibly 2 large incisions and involves invasive dissection
      through muscle and nerve mobilization. This may result in a postoperative
      hematoma and usually substantial pain, posing a challenge for rehabilitation.
      Arthroscopic techniques are less invasive, with potentially fewer complications,
      but are far more technically challenging. Also, most extrinsic and some intrinsic
      causes cannot be adequately addressed through the arthroscope. The outcomes of
      OFER have been found to be superior to those reported after either arthroscopic
      or more conventional open procedures. In addition, we believe that the OFER
      procedure is substantially faster and technically easier than either other open
      or arthroscopic releases, although we are not aware of any studies addressing
      this topic.

PMID- 30233984
TI  - Novel Arthroscopic Tendon Transfers for Posterosuperior Rotator Cuff Tears:
      Latissimus Dorsi and Lower Trapezius Transfers.
AB  - Background: Massive irreparable rotator cuff tears in both the primary and the
      revision setting are challenging problems. There remains controversy over the
      ideal treatment methods for these patients. In the case of an irreparable
      posterosuperior rotator cuff tear, tendon transfers1-12 have emerged as a
      reliable option, with a durable outcome. The most commonly used tendon transfer
      options are the latissimus dorsi (LD)1-6and the lower trapezius (LT)12.
      Description: The LD transfer is performed by first harvesting the LT tendon from
      the humeral shaft. It is critical to release the many adhesions to the muscle
      belly as well as to separate it from the teres major muscle. The tendon is then
      transferred intra-articularly, in an interval between the deltoid and the teres
      minor. The tendon is anchored arthroscopically after preparation of the
      anterolateral aspect of the tuberosity. The LT transfer is performed by
      harvesting the LT muscle and tendon off its insertion on the medial aspect of the
      scapular spine. It should be mobilized to maximize excursion by releasing
      adhesions. An Achilles tendon allograft is anchored into the anterior aspect of
      the greater tuberosity arthroscopically. The Achilles tendon is then secured to
      the LT tendon. Alternatives: In addition to tendon transfer, options
      include:Partial or complete attempted repair13-17.Augmentation or bridging with
      allografts18-23.Superior capsular reconstruction24.Subacromial balloon25.
      Rationale: There remains a paucity of literature comparing tendon transfers with
      alternatives. However, when considering a tendon transfer, certain principles are
      critical in order to achieve an optimal outcome:The recipient and transferred
      tendons must have similar musculotendinous excursion.The recipient and
      transferred tendons should have similar lines of pull.One tendon (the
      transferred) should be designed to replace 1 function (of the recipient).The
      function of the transferred tendon and muscle should be expendable without
      substantial donor site morbidity.The strength of the transferred muscle must be
      at least grade 4.When deciding between the LT and LD transfer, certain
      considerations should be taken into account. The LD transfer has a proven history
      of successfully treating massive irreparable posterosuperior rotator cuff tears
      in studies with long-term follow-up1-6. Alternatively, although the LT transfer
      has only recently gained popularity, it has the advantage of "in-phase" muscle
      function, since the trapezius naturally contracts during shoulder external
      rotation. Furthermore, its line of pull almost completely mimics the
      infraspinatus.

PMID- 30233987
TI  - Congratulations to 2017 EST Award Winners.

PMID- 30233988
TI  - Mini-Invasive Intramedullary Fixation of Displaced Midshaft Clavicle Fractures
      with an Elastic Titanium Nail.
AB  - Background: The treatment of completely displaced midshaft clavicle fractures is
      still controversial, but surgical treatment provides a shorter recovery period
      and higher union rates than nonoperative treatment with a sling1-5. Even though
      the literature does not clearly support surgery for these fractures, surgery is
      becoming more frequent6. Elastic stable intramedullary nailing (ESIN) with a
      titanium nail is a well-documented mini-invasive procedure with functional
      outcomes comparable with those of plate fixation after 1 year but a high rate of
      implant removal of up to 80%6-8. The ideal injury for ESIN is a fracture without
      comminution that is available for surgery within a couple of days. ESIN is also a
      good option for fractures with comminution, but a somewhat slower functional
      recovery during the first 6 months should be expected. Description: The patient
      is placed in beach-chair position with the fluoroscope placed on the injured side
      or cranially in relation to the fracture. The surgeon pushes the skin gently with
      his/her index finger at the jugular fossa before incising it. This places the
      skin incision inferior to the implant. A 1 to 2-cm incision down to the bone is
      then placed about 1 to 2 cm lateral to the sternoclavicular joint. A unicortical
      entry hole is made at the medial end with a 2.5-mm drill bit and then widened and
      directed laterally with an awl. Two reduction forceps are placed percutaneously
      and used by the assistant to align the main fragments. The nail is passed with
      oscillating movements until it is secured into the lateral fragment. If it is not
      possible to obtain a closed reduction, an open reduction is performed. The nail
      is cut short down to the bone, and the myocutaneous layer and skin are closed
      with sutures. Five to 10 mL of bupivacaine is injected into the fracture area for
      postoperative pain management. The arm is placed in a simple sling for comfort. A
      non-weight-bearing active range of motion of <90 degrees  is encouraged.
      Alternatives: Closed completely displaced midshaft clavicle fractures can be
      treated operatively or nonoperatively with a sling. Superior plate fixation is
      well documented, but use of anterior or several mini-fragment plates is also an
      option. There are several intramedullary implant techniques, but most require an
      open reduction. Rationale: Most intramedullary implant methods are open
      procedures, whereas closed reduction and internal fixation is possible with ESIN.
      This ensures preservation of the fracture hematoma and no periosteal stripping,
      in contrast with the open intramedullary techniques. The nail enters the fracture
      medially, which decreases the chance of perioperative pulmonary or neurovascular
      injury. The procedure is less time-consuming than plate fixation, the result is
      cosmetically superior, and the functional outcomes after 1 year are equal. When
      ESIN is used for fractures without intermediary fragments, the functional
      recovery time is equal to that after plate fixation, although it is longer when
      used for fractures with intermediary fragments8.

PMID- 30233989
TI  - Open Surgical Stabilization of Glenohumeral Dislocations.
AB  - Traumatic anterior shoulder dislocations are the most common dislocations of the
      shoulder, and the recurrence rate is high when they are treated nonoperatively in
      young patients (<30 years old). This has led to a trend toward early surgical
      stabilization. Originally open Bankart repair was considered the standard of
      care, with good clinical outcomes and a low recurrence rate. However, the
      majority of Bankart repairs are now performed with newer arthroscopic techniques
      because of their potential advantages and similar results. Both open and
      arthroscopic repairs have been shown to decrease the recurrence rate to 6% to
      23%. Although arthroscopic Bankart repair is now more common, open repair should
      be considered for younger patients participating in contact sports or military
      activity, osseous Bankart lesions, revision cases, shoulder instability with
      "subcritical" (20% to 25%) glenoid bone loss, ligamentous laxity, or cases not
      considered repairable with arthroscopic techniques. Therefore, knowing how to
      perform an open Bankart repair is essential. The major steps of the procedure are
      (1) preoperative planning, (2) induction of anesthesia, (3) patient positioning
      and setup, (4) examination under anesthesia, (5) possible arthroscopic
      examination of the shoulder, (6) incision along the anterior axillary fold, (7)
      exposure using the deltopectoral interval, (8) clavipectoral fascia incision, (9)
      vertical tenotomy of the subscapularis tendon, (10) dissection of the capsule
      from the subscapularis, (11) assessment of the quality of the capsule, (12) "T"
      capsulotomy, (13) repair of the Bankart lesion, (14) anterior capsulorrhaphy,
      (15) subscapularis repair, (16) possible closure of the rotator interval, (17)
      wound closure, and (18) postoperative rehabilitation. Studies have shown that
      surgical stabilization after traumatic anterior shoulder instability decreases
      the recurrence rate, and open and arthroscopic techniques have similar clinical
      outcomes.

PMID- 30233990
TI  - The Kocher-Langenbeck Approach: State of the Art.
AB  - Introduction: The Kocher-Langenbeck approach is the workhorse for the reduction
      and fixation of hip fractures that require fixation via a posterior approach1,2.
      Indications & Contraindications:  Step 1 Preoperative Planning: Review the
      patient's general condition and imaging studies, plan the sequence of reduction
      and fixation, and make sure that all of the necessary equipment is available.
      Step 2 Preparation and Patient Positioning: Induce anesthesia, administer
      intravenous antibiotics as per local hospital protocol, apply antiembolism
      stockings, and insert a Foley catheter to the bladder. Step 3 Kocher-Langenbeck
      Approach: Make an incision that is 15 to 20 cm long and has 2 parts (proximal and
      distal), which are centered over the greater trochanter. Step 4 Fracture
      Reduction and Fixation: The reconstruction of posteriorly based fractures depends
      on the specific fracture type, and the goal is to provide stable column fixation
      and anatomical reconstruction of the acetabular articular surface, with column
      fixation performed before the reconstruction of the posterior wall. Step 5 Wound
      Closure and Postoperative Care: Meticulous hemostasis, application of drains, and
      watertight closure are the final steps of the operation. Results: The Kocher
      Langenbeck approach is the workhorse for the surgical management of acetabular
      fractures and provides sufficient access to the majority of posterior based
      acetabular fractures15. Pitfalls & Challenges: 

PMID- 30233991
TI  - The Ilioinguinal Approach: State of the Art.
AB  - Introduction: The ilioinguinal approach is the standard approach for the open
      reduction and internal fixation of the majority of displaced, anteriorly based
      acetabular fractures as it offers wide access to the acetabulum, is extensile,
      and has been associated with enhanced recovery. Indications & Contraindications: 
      Step 1 Preoperative Planning: Review the patient's general condition and imaging
      studies and plan the sequence of reduction and fixation. Step 2 Preparation and
      Patient Positioning: Position the patient supine on the fracture table, induce
      anesthesia, prepare the surgical field, administer intravenous antibiotics, and
      apply traction. Step 3 Ilioinguinal Approach: Make a long curvilinear incision
      over the affected lower flank, develop the 3 working windows, and reduce and
      stabilize the fracture while protecting the neurovascular structures and the
      bladder (Video 2). Step 4 Fracture Reduction and Fixation: For reduction of a
      both-column acetabular fracture, connect the mobile parts of the acetabulum to
      the iliac segment that is attached to the sacrum, noting that, in most cases, the
      usual sequence involves the reduction of the anterior column to the intact ilium
      followed by the reduction of the posterior column (Video 7). Step 5 Wound Closure
      and Postoperative Aftercare: Perform meticulous hemostasis, apply drains, and
      ensure watertight closure, which are the final steps of the operation (Video 8).
      Results: The ilioinguinal approach remains 1 of the standard approaches for the
      management of acetabular fractures10. Pitfalls & Challenges: 

PMID- 30233992
TI  - Economic value of trees in the estate of the Harewood House stately home in the
      United Kingdom.
AB  - The estates of stately homes or manor houses are an untapped resource for
      assessing the ecosystem services provided by trees. Many of these estates have
      large collections of trees with clear value in terms of carbon storage, runoff
      prevention, and pollution removal along with additional benefits to biodiversity
      and human health. The estate of Harewood House in North Yorkshire represents an
      ideal example of such a stately home with a mixture of parkland and more formally
      planted gardens. The trees in each type of garden were analysed for height,
      diameter at breast height and light exposure. The data were then processed in
      iTrees software to generate economic benefits for each tree in both gardens. The
      analysis found that the larger North Front parkland garden had greater total
      benefits but the more densely planted formal West Garden had the greater per
      hectare value. In total, the trees on Harewood House estate are estimated to
      provide approximately L29 million in ecosystem service benefits. This study is
      the first to analyse the trees of stately homes for economic benefits and
      highlights that the trees are a valuable commodity for the estates. This should
      be considered in future planning and management of such estates.

PMID- 30233993
TI  - Urban waste disposal explains the distribution of Black Vultures (Coragyps
      atratus) in an Amazonian metropolis: management implications for birdstrikes and
      urban planning.
AB  - Collision rates between aircraft and birds have been rising worldwide. The
      increases in both air traffic and population sizes of large-bodied birds in
      cities lacking urban planning result in human-wildlife conflicts, economic loss
      and even lethal casualties. Black Vultures (Coragyps atratus) represent the most
      hazardous bird to Brazilian civil and military aviation on the basis of their
      flight behavior, body mass and consequently physical damage to aircraft following
      collisions. This study investigated how storage apparatus and type of organic
      residue discarded in public street markets modulate the spatial distribution and
      abundance of urban Black Vultures in the largest city in the Amazon (Manaus,
      Brazil). We estimated Black Vulture abundance in relation to the type of solid
      human waste (animal or plant), the type of waste storage containers and market
      sizes in terms of the number of vendor stalls at 20 public markets. We also
      visually quantified the abundance of Black Vultures in urban markets in relation
      to air traffic. Our results suggest that urban solid waste storage procedures
      currently used (or the lack thereof) are related to the occurrence and abundance
      of Black Vultures. Moreover, storage type and the proportion of animal protein
      (red meat and fish) within rubbish bins directly affects foraging aggregations in
      vultures. We recommend that policymakers should invest more efforts in building
      larger and more resistant closable waste containers to avoid organic solid waste
      exposure. We also identified five outdoor markets as urgent priorities to improve
      waste disposal. Finally, our waste management guidelines would not only reduce
      aviation collision risks but also benefit human health and well-being in most
      cities.

PMID- 30233994
TI  - Luciferin production and luciferase transcription in the bioluminescent copepod
      Metridia lucens.
AB  - Bioluminescent copepods are often the most abundant marine zooplankton and play
      critical roles in oceanic food webs. Metridia copepods exhibit particularly
      bright bioluminescence, and the molecular basis of their light production has
      just recently begun to be explored. Here we add to this body of work by
      transcriptomically profiling Metridia lucens, a common species found in
      temperate, northern, and southern latitudes. In this previously molecularly
      uncharacterized species, we find the typical luciferase paralog gene set found in
      Metridia. More surprisingly, we recover noteworthy putative luciferase sequences
      that had not been described from Metridia species, indicating that
      bioluminescence produced by these copepods may be more complex than previously
      known. This includes another copepod luciferase, as well as one from a shrimp.
      Furthermore, feeding experiments using mass spectrometry and 13C labelled L
      tyrosine and L-phenylalanine firmly establish that M. lucens produces its own
      coelenterazine luciferin rather than acquiring it through diet. This
      coelenterazine synthesis has only been directly confirmed in one other copepod
      species.

PMID- 30233995
TI  - Lessepsian migration and parasitism: richness, prevalence and intensity of
      parasites in the invasive fish Sphyraena chrysotaenia compared to its native
      congener Sphyraena sphyraena in Tunisian coastal waters.
AB  - Background: Parasites can play various roles in the invasion of non-native
      species, but these are still understudied in marine ecosystems. This also applies
      to invasions from the Red Sea to the Mediterranean Sea via the Suez Canal, the so
      called Lessepsian migration. In this study, we investigated the role of parasites
      in the invasion of the Lessepsian migrant Sphyraena chrysotaenia in the Tunisian
      Mediterranean Sea. Methods: We compared metazoan parasite richness, prevalence
      and intensity of S. chrysotaenia (Perciformes: Sphyraenidae) with infections in
      its native congener Sphyraena sphyraena by sampling these fish species at seven
      locations along the Tunisian coast. Additionally, we reviewed the literature to
      identify native and invasive parasite species recorded in these two hosts.
      Results: Our results suggest the loss of at least two parasite species of the
      invasive fish. At the same time, the Lessepsian migrant has co-introduced three
      parasite species during the initial migration to the Mediterranean Sea, that are
      assumed to originate from the Red Sea of which only one parasite species has been
      reported during the spread to Tunisian waters. In addition, we found that the
      invasive fish has acquired six parasite species that are native in the
      Mediterranean Sea. However, parasite richness, prevalence and intensity were
      overall much lower in the invasive compared to the native fish host in the
      Mediterranean Sea. Discussion: These results suggest that the Lessepsian migrant
      may affect native fish hosts by potentially altering the dynamics of native and
      invasive parasite-host interactions via parasite release, parasite co
      introduction and parasite acquisition. They further suggest that the lower
      infection levels in the invasive fish may result in a competitive advantage over
      native fish hosts (enemy release hypothesis). This study demonstrates that cross
      species comparisons of parasite infection levels are a valuable tool to identify
      the different roles of parasites in the course of Lessepsian migrations.

PMID- 30233996
TI  - Cerebral Abscess following Mechanical Thrombectomy for Ischemic Stroke: Report of
      a Case and Review of Literature.
AB  - Cerebral infections have been reported after endovascular interventions such as
      embolization and coiling. Such complications are extremely rare and only one
      other case has been reported in a patient who underwent an endovascular therapy
      for ischemic stroke. We report a 32-year-old woman, who presented to our hospital
      with headaches lasting four weeks after an endovascular intervention for ischemic
      stroke via mechanical thrombectomy. Further investigations revealed a cerebral
      abscess in the area of the infarct. She was effectively treated with antibiotics
      in combination with stereotactic drainage and was discharged after she made a
      good recovery. A review of literature on cerebral abscesses after minimally
      invasive procedures such as endovascular intervention was also done and is being
      presented in this paper. A cerebral abscess can occur rarely after endovascular
      interventions. A high degree of suspicion is important in identifying patients
      with an abscess and appropriate treatment can prevent significant morbidity or
      even death.

PMID- 30233997
TI  - Neighborhood socioeconomic characteristics, healthcare spatial access, and
      emergency department visits for ambulatory care sensitive conditions for elderly.
AB  - The objective of this study is to explore relationships among neighborhood
      socioeconomic characteristics (for example, income and ethnicity), spatial access
      to health care, and emergency department (ED) visits for ambulatory care
      sensitive conditions (ACSC) for adults aged 65 years and over. ED visit data were
      from 15 counties in the Texas Coastal Bend from September 1, 2009 and August 1,
      2012. ED visits for ACSC that were common for elderly were estimated based on
      Agency for Healthcare Research and Quality's (AHRQ's) ACSC and Prevention Quality
      Indicators. The U.S. Census American Community Service (ACS) data provided
      neighborhood socioeconomic characteristics. Spatial access to general practices
      and to hospitals, respectively at the zip code level were estimated using the
      enhanced two-step floating catchment area method. Using multivariable regression
      models, we estimated associations of elderly ACSC ED visits with neighborhood
      socioeconomic characteristics and spatial accessibility of healthcare. We found
      higher rates of elderly ACSC ED visits are significantly associated with higher
      rates of elderly Hispanic and poverty at the zip code level. Spatial access to
      general practices and hospitals play inverse roles in the rate of elderly ACSC ED
      visits. Poorer access to general practices but easier access to hospitals
      contributes to the higher elderly ACSC ED rate at the zip code level.
      Neighborhood socioeconomic characteristics and spatial access to healthcare
      affect the rate of elderly ACSC ED visits. Research informing policy action is
      needed to decrease racial/ethnic and economic disadvantage and increase equitable
      spatial access to primary care for the elderly.

PMID- 30233998
TI  - Factors influencing application of behavioural science evidence by public health
      decision-makers and practitioners, and implications for practice.
AB  - The National Institute of Health and Care Excellence (NICE) in the UK recommends
      behavioural science evidence underpins public health improvement services. In
      practice, level of implementation varies. This study is the first to explore
      factors affecting use of behaviour-specific evidence by public health decision
      makers and practitioners for design and delivery of health improvement services.
      Twenty semi-structured interviews were conducted, along with a review of the
      commissioning cycle with public health decision-makers and practitioners across a
      range of health improvement fields (e.g. weight management). Interviews were
      informed and analysed using the Theoretical Domains Framework (TDF). Limited
      comprehension of behaviour change, challenges identifying specific behaviour
      change strategies and translating research into practice were prevalent. Local
      authority processes encouraged uptake of evidence to justify solutions as opposed
      to evidence-driven decision-making. Some decision-makers perceived research
      evidence may stifle innovation and overwhelm practitioners. Potential
      facilitators of research use included: ensuring uptake and implementation of
      evidence is compulsory within commissioning and its potential to show value for
      money. A strong belief in local evidence and achieving outcomes were identified
      as barriers to research evidence uptake. Social and environmental challenges
      included cultural, political, and workload pressures and journal article
      accessibility. Embedding behavioural science systematically into public health
      practice requires changes throughout the public health system; from priorities
      set by national public health leaders to the way in which relevant evidence is
      disseminated. Framing factors affecting use of behavioural science evidence using
      the TDF is helpful for identifying the range of interventions and support needed
      to affect change.

PMID- 30233999
TI  - Regional differences in BMI, obesity, and exercise frequency in a large veteran
      service organization: A secondary analysis of new veteran member surveys from
      Team Red, White & Blue.
AB  - The purpose of the present study was to examine regional differences in average
      self-reported BMI, obesity prevalence, and frequent exercise (FE) among members
      of Team Red, White, and Blue (Team RWB) - a military veteran service organization
      founded to increase physical activity in veterans. A total of 10,015 military
      veterans participated in a needs assessment conducted by Team RWB between
      December 2014 and August 2016. Multivariate regression analysis with bootstrapped
      coefficients revealed that: BMI was highest in the Midwest region (M = 28.282) of
      the United States, F(20, 9882) = 105.560, p < 0.001; obesity prevalence was
      highest in the Southcentral (32.300%) and Southeast (32.200%) regions, x2(9731) =
      10,850, p < 0.001; and FE was most prevalent in the Mid-Atlantic region (67.3%),
      x2(9882) = 11,291, p < 0.001.The results of this study closely mirror results
      found in studies of the general population. A better understanding of the
      geographic distribution of these outcomes could guide the targeting of sub
      populations for public health programs. In particular, Team Red, White & Blue
      community growth and other fitness based public health programs could be expanded
      to reach more veterans.

PMID- 30234000
TI  - Utilizing wearable technology to increase physical activity in future physicians:
      A randomized trial.
AB  - This study examined the use of activity trackers alone or combined with weekly
      communication through email to improve activity and body composition over one
      academic year in medical students. This randomized clinical trial conducted at
      the New York Institute of Technology from July 7, 2016 through June 4, 2017
      enrolled 120 medical students. The first group (Fitbit-Plus) wore activity
      trackers and received weekly emails offering fitness challenges and lifestyle
      modification challenges. The second group (Fitbit-Only) received only activity
      trackers and did not receive weekly emails. The third group (Control) was asked
      not to purchase an activity tracker of any kind throughout the study. All groups
      had a body composition analysis prior to the start of the academic year and at
      the end of the first academic year. Outcome measures included step count and body
      composition (body fat percentage and lean body mass). The results showed the
      overall mean daily steps were greater in the Fitbit-Plus group than the Fitbit
      Only group for the academic year (7429 +/- 2833 vs. 6483 +/- 2359) with only
      months April and May showing a significant difference between the groups (p =
      0.011; p = 0.044). Body fat percentage decreased in the Fitbit-Plus overweight
      women (2.1 +/- 1.6%) lean body mass increased in the Fitbit-Plus group in
      overweight men (2.4 +/- 4.6 lbs.). A subsequent finding of this study showed
      improved body composition in a small sub-group of over-weight students. Weekly
      behavioral challenges combined with an activity tracker increased step count in
      medical students compared to an activity tracker alone. Clinicaltrials.gov
      Identifier: NCT02778009.

PMID- 30234002
TI  - Enormous mucocele following colonic graft neovagina formation in a transwoman.

PMID- 30234001
TI  - Associations of total amount and patterns of objectively measured sedentary
      behavior with performance-based physical function.
AB  - Although greater sedentary time has been found to be associated with negative
      health impacts, little is known whether the specific pattern of sedentary
      behavior (i.e. sedentary bouts, breaks and durations) are associated with
      physical function among older adults. The present study examined the associations
      between objectively measured sedentary behavior and physical function among older
      Japanese adults. A total of 174 male and 107 female community-dwelling older
      Japanese adults aged 65-84 years (mean age: 74.5 +/- 5.2 years) were recruited.
      Sedentary behavior and physical activity were assessed using a triaxial
      accelerometer. Physical function was measured through hand grip strength, eye
      open one leg standing, 5-m walking, and timed up and go tests. Forced-entry
      multiple linear regression models adjusted for potential confounders were
      performed. After adjustment, total daily sedentary time and duration of prolonged
      sedentary bouts (both >= 30 min) were positively associated with time spent on
      the 5-m walking stage and timed up and go tests in older women; however, no
      significant associations were observed in older men or the whole sample. This
      paper highlights the importance of developing sedentary behavior change
      strategies for interventions aiming to improve mobility in in older women.
      Further evidence from a prospective study is required to establish directions of
      causality between sedentary behavior and mobility.

PMID- 30234003
TI  - A case of retroperitoneal vascular malformation.

PMID- 30234004
TI  - Isolated central nervous system metastasis in pediatric Wilms' tumor: A case
      report and review of literature.

PMID- 30234005
TI  - Equine degenerative myeloencephalopathy: prevalence, impact, and management.
AB  - Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy is an
      inherited neurodegenerative disorder affecting many horse breeds. Clinical signs
      include a symmetric ataxia and an abnormal stance at rest, similar to cervical
      vertebral compressive myelopathy, equine protozoal myeloencephalitis, and equine
      herpesvirus 1 myeloencephalopathy. This review will provide an update on the
      disease prevalence, management, impact, and ongoing research.

PMID- 30234006
TI  - Evaluation of ADA activity as a potential marker of disease severity in psoriasis
      patients.
AB  - Background: Psoriasis is a dermatological disorder with a multifactorial origin
      and is associated with many biochemical and immunological changes. Purpose: This
      study aimed to examine the association of serum ADA activity, uric acid (UA), and
      high-sensitivity CRP (hs-CRP) with psoriasis and the role of ADA in disease
      severity. Materials and methods: In this comparative cross-sectional study, 50
      clinically and histopathologically diagnosed psoriasis patients and 50 age- and
      sex-matched healthy controls were enrolled. Blood samples were taken and analysis
      of the biochemical parameters was performed according to Giuisti and Galanti
      method, uricase and ELISA technique for ADA activity, UA, and hs-CRP,
      respectively. The severity of the disease was scored according to Psoriasis Area
      and Severity Index (PASI). Statistical analysis of differences within and between
      the study groups was carried out using the Student's t-test, one-way post hoc
      ANOVA, and Pearson's correlation. Linear regression was used to establish the
      independent association of ADA with disease severity. Results: The serum ADA
      activity, UA, and hs-CRP levels of the psoriatic patients were found to be
      significantly higher (P<0.001). hs-CRP was positively correlated with ADA and UA
      in patients (P<0.001). There was no significant difference in total cholesterol,
      low-density lipoprotein, and triacylglycerol in psoriasis patients, whereas we
      noted a decreased high-density lipoprotein level in psoriasis patients as
      compared to controls. Linear regression showed that ADA was independently
      associated with the disease severity and was statistically significant (P<0.001).
      Conclusion: ADA activity was positively and significantly associated with the
      severity of psoriasis, therefore, it could be suggested as a marker for disease
      severity in psoriasis patients.

PMID- 30234007
TI  - CO2 Transoral Microsurgery for Supraglottic Squamous Cell Carcinoma.
AB  - The present study analyzed the results of the endoscopic approach to T1, T2 and
      selected T3 supraglottic carcinoma with the aim of reviewing functional and
      oncologic outcomes after different types of endoscopic supraglottic
      laryngectomies. This is a retrospective clinical study of 42 consecutive patients
      (mean age of 61.8 years, 33 males, 9 females) treated by the senior author for
      supraglottic squamous cell carcinoma with a transoral CO2 laser approach and
      reviewed from November 2010 to September 2017. Surgical procedures were
      classified according to the European Laryngological Society. In addition to the
      standardized transoral supraglottic laryngectomies, we introduced a modified type
      IVb by sparing the inferior third of the arytenoid if not directly involved in
      the tumor. Swallowing was evaluated with the Swallowing Performance Status Scale
      reported by the Multinational Association of Supportive Care in
      Cancer/International Society of Oral Oncology. Survival probabilities were
      estimated using Kaplan-Meier curves. Two type I, 2 type IIa, 2 type IIb, 3 type
      IIIa, 12 type IIIb, 13 type IVa, 3 type modified IVb, and 5 type IVb supraglottic
      laryngectomies were performed. Twenty-one patients (50%) underwent primary neck
      dissection. The pathologic TNM classification according to the 8th edition of the
      American Joint Committee on Cancer system was as follows: 9 pT1cN0, 2 pT1N0, 1
      pT1N1, 7 pT2cN0, 1 rypT2cN0, 9 pT2N0, 4 pT2N1, 2 ypT2N1, 2 pT3cN0, 2 rypT3cN0, 1
      pT3N1, and 2 pT3N2b. Mean follow-up was 3.4 years (range of 9 months to 6 years).
      According to the Kaplan-Meier analysis, 5-year disease-specific survival, local
      relapse-free survival, nodal-relapse-free survival, overall laryngeal
      preservation and overall survival of patients without previous head and neck
      radiotherapy/open surgery were 100%, 95.2%, 87.8%, 100%, and 64.6%, respectively.
      Patients who underwent type I, IIa, and IIb resections (n = 6) started oral
      feeding the day after surgery, patients who underwent type III-IVb modified
      resections (n = 31) started oral feeding 3-4 days after surgery, and patients who
      underwent standard type 4b resections (n = 5) started oral feeding 7 days after
      surgery. Three months after surgery, patients without a clinical history of
      previous head and neck radiotherapy/open surgery who underwent type III, IVa, and
      modified IVb resections showed significantly better swallowing compared to
      patients who underwent standard type IVb resection: grade 4-6 impairment of
      swallowing in 8 and 66.7% of cases, respectively (p = 0.006072); patients with a
      clinical history of previous head and neck radiotherapy/open surgery who
      underwent type III, IVa, and modified IVb resections showed not statistically
      significant better swallowing compared to patients who underwent standard type
      IVb resection: grade 4-6 impairment of swallowing at 3 months in 16.7% and 50% of
      cases, respectively (p = 0.23568). Transoral CO2 laser supraglottic laryngectomy
      is an oncologic sound alternative to traditional open neck surgery and chemo
      radiotherapy. Recovery of swallowing is significantly worsened after total
      resection of the arytenoid. Modified type IVb procedure leaving intact, when
      possible, the inferior third of the arytenoid and consequently the glottic
      competence, improves functional outcome.

PMID- 30234008
TI  - The Complex Puzzle of Interactions Among Functional Food, Gut Microbiota, and
      Colorectal Cancer.
AB  - Colorectal cancer exerts a strong influence on the epidemiological panorama
      worldwide, and it is directly correlated to etiologic factors that are
      substantiated by genetic and environmental elements. This complex mixture of
      factors also has a relationship involving the structural dependence and
      composition of the gut microbiome, leading to a dysbacteriosis process that may
      evolve to serious modifications in the intestinal lining, eventually causing the
      development of a neoplasm. The gastrointestinal tract presents defense strategies
      and immunological properties that interfere in intestinal permeability,
      inhibiting the bacterial translocation, thus maintaining the integrity of
      intestinal homeostasis. The modulation of the intestinal microbiome and the
      extinction of risk factors associated with intestinal balance losses, especially
      of environmental factors, make cell and defense alterations impossible. This
      modulation may be conducted by means of functional foods in the diet, especially
      soluble fibers, polyunsaturated fatty acids, antioxidants and prebiotics that
      signal immunomodulatory effects in the intestinal microbiota, with preventive and
      therapeutic action for colorectal cancer. In summary, this review focuses on the
      importance of dietary modulation of the intestinal microbiota as an instrument
      for dysbacteriosis and, consequently, for the prevention of colorectal cancer,
      suggesting anticarcinogenic, and antiangiogenic properties. Among the intestinal
      modulating agents considered here are functional foods, especially flaxseed, oat
      and soy, composing a Bioactive Food Compound.

PMID- 30234010
TI  - Role, Targets and Regulation of (de)nitrosylation in Malignancy.

PMID- 30234011
TI  - Brain Radiation Necrosis: Current Management With a Focus on Non-small Cell Lung
      Cancer Patients.
AB  - As the prognosis of metastatic non-small cell lung cancer (NSCLC) patients is
      constantly improving with advances in systemic therapies (immune checkpoint
      blockers and new generation of targeted molecular compounds), more attention
      should be paid to the diagnosis and management of treatments-related long-term
      secondary effects. Brain metastases (BM) occur frequently in the natural history
      of NSCLC and stereotactic radiation therapy (SRT) is one of the main efficient
      local non-invasive therapeutic methods. However, SRT may have some disabling side
      effects. Brain radiation necrosis (RN) represents one of the main limiting
      toxicities, generally occurring from 6 months to several years after treatment.
      The diagnosis of RN itself may be quite challenging, as conventional imaging is
      frequently not able to differentiate RN from BM recurrence. Retrospective studies
      have suggested increased incidence rates of RN in NSCLC patients with oncogenic
      driver mutations [epidermal growth factor receptor (EGFR) mutated or anaplastic
      lymphoma kinase (ALK) positive] or receiving tyrosine kinase inhibitors. The risk
      of immune checkpoint inhibitors in contributing to RN remains controversial.
      Treatment modalities for RN have not been prospectively compared. Those include
      surveillance, corticosteroids, bevacizumab and local interventions (minimally
      invasive laser interstitial thermal ablation or surgery). The aim of this review
      is to describe and discuss possible RN management options in the light of the
      newly available literature, with a particular focus on NSCLC patients.

PMID- 30234012
TI  - Phenotypic Basis for Matrix Stiffness-Dependent Chemoresistance of Breast Cancer
      Cells to Doxorubicin.
AB  - The persistence of drug resistant cell populations following chemotherapeutic
      treatment is a significant challenge in the clinical management of cancer.
      Resistant subpopulations arise via both cell intrinsic and extrinsic mechanisms.
      Extrinsic factors in the microenvironment, including neighboring cells,
      glycosaminoglycans, and fibrous proteins impact therapy response. Elevated levels
      of extracellular fibrous proteins are associated with tumor progression and cause
      the surrounding tissue to stiffen through changes in structure and composition of
      the extracellular matrix (ECM). We sought to determine how this progressively
      stiffening microenvironment affects the sensitivity of breast cancer cells to
      chemotherapeutic treatment. MDA-MB-231 triple negative breast carcinoma cells
      cultured in a 3D alginate-based hydrogel system displayed a stiffness-dependent
      response to the chemotherapeutic doxorubicin. MCF7 breast carcinoma cells
      cultured in the same conditions did not exhibit this stiffness-dependent
      resistance to the drug. This differential therapeutic response was coordinated
      with nuclear translocation of YAP, a marker of mesenchymal differentiation. The
      stiffness-dependent response was lost when cells were transferred from 3D to
      monolayer cultures, suggesting that endpoint ECM conditions largely govern the
      response to doxorubicin. To further examine this response, we utilized a platform
      capable of dynamic ECM stiffness modulation to allow for a change in matrix
      stiffness over time. We found that MDA-MB-231 cells have a stiffness-dependent
      resistance to doxorubicin and that duration of exposure to ECM stiffness is
      sufficient to modulate this response. These results indicate the need for
      additional tools to integrate mechanical stiffness with therapeutic response and
      inform decisions for more effective use of chemotherapeutics in the clinic.

PMID- 30234013
TI  - Postoperative Cavity Stereotactic Radiosurgery for Brain Metastases.
AB  - During the past decade, tumor bed stereotactic radiosurgery (SRS) after surgical
      resection has been increasingly utilized in the management of brain metastases.
      SRS has risen as an alternative to adjuvant whole brain radiation therapy (WBRT),
      which has been shown in several studies to be associated with increased
      neurotoxicity. Multiple recent articles have shown favorable local control rates
      compared to those of WBRT. Specifically, improvements in local control can be
      achieved by adding a 2 mm margin around the resection cavity. Risk factors that
      have been established as increasing the risk of local recurrence after resection
      include: subtotal resection, larger treatment volume, lower margin dose, and a
      long delay between surgery and SRS (>3 weeks). Moreover, consensus among experts
      in the field have established the importance of (a) fusion of the pre-operative
      magnetic resonance imaging scan to aid in volume delineation (b) contouring the
      entire surgical tract and (c) expanding the target to include possible
      microscopic disease that may extend to meningeal or venous sinus territory. These
      strategies can minimize the risks of symptomatic radiation-induced injury and
      leptomeningeal dissemination after postoperative SRS. Emerging data has arisen
      suggesting that multifraction postoperative SRS, or alternatively, preoperative
      SRS could provide decreased rates of radiation necrosis and leptomeningeal
      disease. Future prospective randomized clinical trials comparing outcomes between
      these techniques are necessary in order to improve outcomes in these patients.

PMID- 30234009
TI  - Fructose 2,6-Bisphosphate in Cancer Cell Metabolism.
AB  - For a long time, pioneers in the field of cancer cell metabolism, such as Otto
      Warburg, have focused on the idea that tumor cells maintain high glycolytic rates
      even with adequate oxygen supply, in what is known as aerobic glycolysis or the
      Warburg effect. Recent studies have reported a more complex situation, where the
      tumor ecosystem plays a more critical role in cancer progression. Cancer cells
      display extraordinary plasticity in adapting to changes in their tumor
      microenvironment, developing strategies to survive and proliferate. The
      proliferation of cancer cells needs a high rate of energy and metabolic
      substrates for biosynthesis of biomolecules. These requirements are met by the
      metabolic reprogramming of cancer cells and others present in the tumor
      microenvironment, which is essential for tumor survival and spread. Metabolic
      reprogramming involves a complex interplay between oncogenes, tumor suppressors,
      growth factors and local factors in the tumor microenvironment. These factors can
      induce overexpression and increased activity of glycolytic isoenzymes and
      proteins in stromal and cancer cells which are different from those expressed in
      normal cells. The fructose-6-phosphate/fructose-1,6-bisphosphate cycle, catalyzed
      by 6-phosphofructo-1-kinase/fructose 1,6-bisphosphatase (PFK1/FBPase1)
      isoenzymes, plays a key role in controlling glycolytic rates. PFK1/FBpase1
      activities are allosterically regulated by fructose-2,6-bisphosphate, the product
      of the enzymatic activity of the dual kinase/phosphatase family of enzymes: 6
      phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFKFB1-4) and TP53-induced
      glycolysis and apoptosis regulator (TIGAR), which show increased expression in a
      significant number of tumor types. In this review, the function of these
      isoenzymes in the regulation of metabolism, as well as the regulatory factors
      modulating their expression and activity in the tumor ecosystem are discussed.
      Targeting these isoenzymes, either directly or by inhibiting their activating
      factors, could be a promising approach for treating cancers.

PMID- 30234014
TI  - Global Inequities in Precision Medicine and Molecular Cancer Research.
AB  - Precision medicine based upon molecular testing is heralded as a revolution in
      how cancer is prevented, diagnosed, and treated. Large efforts across the world
      aim to conduct comprehensive molecular profiling of disease to inform preclinical
      models, translational research studies and clinical trials. However, most studies
      have only been performed in patients from high-income countries. As the burden on
      non-communicable diseases increases, cancer will become a pressing burden across
      the world, disproportionately affecting low-middle income settings. There is
      emerging evidence that the molecular landscape of disease differs geographically
      and by genetic ancestry, which cannot be explained by environmental factors
      alone. There is a lack of good quality evidence that characterises the molecular
      landscape of cancers found in low-middle income countries. As cancer medicine
      becomes increasingly driven by molecular alterations in high-income settings, low
      income settings may become left behind. Further efforts on an international scale
      must be made by researchers, funders, and policymakers to ensure cancer research
      addresses disease across the world, so models are not limited to subtypes of
      disease found in high-income countries. In this review, we discuss differences
      found in the molecular profiles of tumours worldwide and the implication this has
      for the future of global cancer care. Finally, we identify several barriers
      currently limiting progress in this field and innovative solutions, which may
      address these shortcomings.

PMID- 30234015
TI  - MicroRNAs and DNA-Damaging Drugs in Breast Cancer: Strength in Numbers.
AB  - MicroRNAs are a class of small non-coding regulatory RNAs playing key roles in
      cancer. Breast cancer is the most common female malignancy worldwide and is
      categorized into four molecular subtypes: luminal A and B, HER2+ and triple
      negative breast cancer (TNBC). Despite the development of multiple targeted
      therapies for luminal and HER2+ breast tumors, TNBC lacks specific therapeutic
      approaches, thus they are treated mainly with radio- and chemotherapy. The
      effectiveness of these therapeutic regimens is based on their ability to induce
      DNA damage, which is differentially resolved and repaired by normal vs. cancer
      cells. Recently, drugs directly targeting DNA repair mechanisms, such as PARP
      inhibitors, have emerged as attractive candidates for the future molecular
      targeted-therapy in breast cancer. These compounds prevent cancer cells to
      appropriate repair DNA double strand breaks and induce a phenomenon called
      synthetic lethality, that results from the concurrent inhibition of PARP and the
      absence of functional BRCA genes which prompt cell death. MicroRNAs are relevant
      players in most of the biological processes including DNA damage repair
      mechanisms. Consistently, the downregulation of DNA repair genes by miRNAs have
      been probe to improve the therapeutic effect of genotoxic drugs. In this review,
      we discuss how microRNAs can sensitize cancer cells to DNA-damaging drugs,
      through the regulation of DNA repair genes, and examine the most recent findings
      on their possible use as a therapeutic tools of treatment response in breast
      cancer.

PMID- 30234016
TI  - Osmolyte Induced Tumorigenesis and Metastasis: Interactions With Intrinsically
      Disordered Proteins.
AB  - In spite of a great deal of work, the biochemical mechanisms underlying
      tumorigenesis and metastasis are not yet fully understood. Specifically regarding
      metastasis many authors consider that malignancy is caused by the accumulation of
      mutations. However, evidence is gathering to show that tumors are composed of
      heterogeneous cell populations subjected to selective pressures. In this micro
      evolutionary scenario, intra- and extra-cellular selective pressures will
      determine which subpopulations of tumor cells will thrive and be able to
      dissociate from the tumor as autonomous metastatic cells. We propose here that
      alteration of conformations of transcription factors confer novel non-canonical
      functions that may induce oncogenesis and metastasis in a mutation independent
      manner. We argue that the functional plasticity of transcription factors is due
      to intrinsically disordered domains (IDRs) of proteins. IDRs prevent spontaneous
      folding of proteins into well-defined three-dimensional structures. Because most
      transcription factors contain IDRs, each could potentially interact with many
      ligands. This high degree of functional pleiotropy would then be ultimately
      responsible for the metastatic phenotype. The conformations of proteins can be
      altered by chemical chaperones collectively known as osmolytes. Osmolytes are
      small organic molecules permeable through biological membranes that can
      accumulate in cells, increase the thermodynamic stability of proteins, modulate
      enzyme activity and prevent protein aggregation. Thus, by modifying IDRs,
      osmolytes could subvert the homeostatic regulatory network of cells. Untargeted
      metabolomic analysis of oral cancer cells showed that those with the greatest
      metastatic potential contained several osmolytes that were absent in the non
      metastatic cells. We hypothesize that high concentrations of osmolytes might
      promote conformational alterations of transcription factors that favor metastatic
      behavior. This hypothesis is eminently testable by investigating whether: (a) the
      intracellular microenvironment of metastatic cells differs from non-metastatic
      cells and whether osmolytes are responsible for this change and (b) high
      intracellular concentrations of osmolytes are sufficient to induce structural
      modifications in regulatory protein so as to establish novel interactive networks
      that will constitute the metastatic phenotype. Synthetic cell penetrating
      peptides mimicking IDRs could act as sensitive probes. By exposing the peptides
      to the microenvironments of living tumor and metastatic tumor cells one should be
      able to compare the chemical shifts as revealed by spectra obtained by nuclear
      magnetic resonance (NMR).

PMID- 30234018
TI  - Comparison of Skull Motions in Six Degrees of Freedom Between Two Head Supports
      During Frameless Radiosurgery by CyberKnife.
AB  - Introduction: Maintaining immobilization to minimize skull motion is important
      during frameless radiosurgery. This study aimed to compare the intrafractional
      skull motions between two head supports. Methods: With 6D skull tracking system,
      4,075 image records from 45 patients receiving radiosurgery by CyberKnife were
      obtained. Twenty-three patients used TIMO head supports (CIVCO) (Group A) and
      twenty-two patients used Silverman head supports (CIVCO) with MoldCare cushions
      (ALCARE) (Group B). The skull motions in X (superior-inferior), Y (right-left), Z
      (anterior-posterior) axes, 3D (three-dimensional) vector, Roll, Pitch and Yaw
      between the two groups were compared and the margins of planning target volume
      were estimated. Results: The translational motions in Group A were similar in
      three axes at initial but became different after 10 min, and those in Group B
      were less prominent in the Y axis. The rotational errors in Group A were most
      obvious in Yaw, but those in Group B were stationary in three axes. The motions
      in the X axis, 3D vector, Pitch and Yaw in Group B were significantly smaller
      than those in Group A; conversely, the motions in the Z axis in Group B were
      larger. To cover the 95% confidence intervals, margins of 0.77, 0.79, and 0.40 mm
      in the X, Y, and Z axes, respectively, were needed in Group A, and 0.69, 0.50,
      and 0.51 mm were needed in Group B. Conclusions: Both head supports could provide
      good immobilization during the frameless radiosurgery. Silverman head support
      with MoldCare cushion was better than TIMO head support in the superior-inferior
      direction, 3D vector, Pitch and Yaw axes, but worse in the anterior-posterior
      direction.

PMID- 30234017
TI  - Prophylactic vs. Therapeutic Treatment With P2Et Polyphenol-Rich Extract Has
      Opposite Effects on Tumor Growth.
AB  - Polyphenols have tumoricidal effects via anti-proliferative, anti-angiogenic and
      cytotoxic mechanisms and have recently been demonstrated to modulate the immune
      response through their anti- or pro- oxidant activity. Nevertheless, it remains
      controversial whether antioxidant-rich supplements have real beneficial effects
      on health, especially in complex diseases such as cancer. We previously
      identified a polyphenol-rich extract obtained from Caesalpinia spinosa (P2Et)
      with anti-tumor activity in both breast carcinoma and melanoma. The present work
      evaluated the ability of P2Et extract to modulate the immune system in either the
      steady state or following tumor challenge. We found that the prophylactic
      treatment of healthy mice increased the number of CD4+ and CD8+ activated T, NK,
      regulatory T, dendritic and myeloid-derived suppressor cells in lymphoid organs
      together with a significant increase in plasma IL-6. Interestingly, this pre
      conditioning of the host immune system with P2Et did not involve a protective
      effect against the control of tumor growth and metastasis in transplantable
      models of melanoma (B16) and breast cancer (4T1), but in contrast, a detrimental
      effect was observed in both models. We further demonstrated that this effect was
      at least partly due to an increase in regulatory T cells, myeloid-derived
      suppressor cells, and proinflammatory cytokines, with a concomitant decrease in
      CD4+ and CD8+ T cells. Taken together, these results suggest that the anti-tumor
      and immunomodulation properties of the P2Et extract critically depend on the
      presence of the tumor and might be mediated by the complex interactions between
      the tumor cells and the other components of the tumor microenvironment.

PMID- 30234019
TI  - Novel Nomogram for Preoperative Prediction of Early Recurrence in Intrahepatic
      Cholangiocarcinoma.
AB  - Introduction: The emerging field of "radiomics" has considerable potential in
      disease diagnosis, pathologic grading, prognosis evaluation, and prediction of
      treatment response. We aimed to develop a novel radiomics nomogram based on
      radiomics features and clinical characteristics that could preoperatively predict
      early recurrence (ER) of intrahepatic cholangiocarcinoma (ICC) after partial
      hepatectomy. Methods: A predictive model was developed from a training cohort
      comprising 139 ICC patients diagnosed between January 2010 and June 2014.
      Radiomics features were extracted from arterial-phase image of contrast-enhanced
      magnetic resonance imaging. Feature selection and construction of a "radiomics
      signature" were through Spearman's rank correlation and least absolute shrinkage
      and selection operator (LASSO) logistic regression. Combined with clinical
      characteristics, a radiomics nomogram was developed with multivariable logistic
      regression. Performance of the nomogram was evaluated with regard to
      discrimination, calibration, and clinical utility. An independent validation
      cohort involving 70 patients recruited from July 2014 to March 2016 was used to
      evaluate the utility of the nomogram developed. Results: The radiomics signature,
      consisting of nine features, differed significantly between ER patients and non
      ER patients in training and validation cohorts. The area under the curve (AUC) of
      the radiomics signature in training and validation cohorts was 0.82 (confidence
      interval [CI], 0.74-0.88) and 0.77 (95% CI, 0.65-0.86), respectively. The AUC of
      the radiomics nomogram combining the radiomics signature and clinical stage in
      the two cohorts was 0.90 (95%CI, 0.83-0.94) and 0.86 (95% CI, 0.76-0.93),
      respectively. Decision curve analysis confirmed the clinical usefulness of the
      radiomics nomogram. Conclusion: The non-invasive radiomics nomogram developed
      using the radiomics signature and clinical stage could be used to predict ER of
      ICC after partial hepatectomy.

PMID- 30234020
TI  - Clinical Significance of Potential Unidentified HLA-G Isoforms Without alpha1
      Domain but Containing Intron 4 in Colorectal Cancer Patients.
AB  - The ectopic HLA-G expression in malignancies has been extensively explored and
      clinical significance of the molecule was widely acknowledged. Besides previously
      well-documented seven isoforms (HLA-G1~-G7), other novel isoforms of HLA-G have
      been reported but their clinical relavenace remians evaluated. In this study,
      lesion HLA-G expression in 379 case-matched serial section primary colorectal
      cancers (CRC) were evaluated with mAb 4H84 (recognizing an epitope in HLA-G
      alpha1 domain), and mAb 5A6G7 (recognizing an epitope encoded by intron 4),
      respectively. Data showed that HLA-G positive staining with mAbs 4H84 and 5A6G7
      was 70.7 and 60.4%, respectively. When percentage of HLA-G expression detected
      with mAb 4H84 subtracted that with mAb 5A6G7, the difference (DeltaHLA-G) with
      negative (DeltaHLA-Gneg), comparable (DeltaHLA-Gcom) and positive (DeltaHLA-Gpos)
      were observed in 64 (16.9%), 159 (42.0%), and 156 (41.2%) cases, respectively.
      Noteworthy, unexpected immunostaining was observed in 44 (11.6%) lesions that no
      staining was detected with mAb 4H84 but positive with mAb 5A6G7
      (4H84neg5A6G7pos). This staining pattern was unpredictable because all seven
      known HLA-G isoforms containing the alpha 1 domain could be recognized by the mAb
      4H84. Moreover, patients with DeltaHLA-Gneg had obviously better survival than
      those with DeltaHLA-Gcom and DeltaHLA-Gpos (p = 0.017), and DeltaHLA-G could be
      an independent prognostic factor for CRC patients (p = 0.008). Our findings
      provides the first report that potential unidentified HLA-G isoforms is of
      distinct clinical significance in CRC patients.

PMID- 30234021
TI  - Host MicroRNA hsa-miR-494-3p Promotes EV71 Replication by Directly Targeting
      PTEN.
AB  - Many cellular processes are driven by spatially and temporally regulated
      microRNAs (miRNAs)-dependent signaling events. Substantial evidence collected
      over the years indicates that miRNAs are pivotal regulators that contribute to
      the initiation and development of EV71-related disorders. Importantly, so far, no
      clinical trial has been undertaken to address the effect of miRNAs on EV71
      related diseases. In this study, we show that EV71 infection results in up
      regulation of hsa-miR-494-3p levels, and that EV71-induced hsa-miR-494-3p impacts
      PI3K/Akt signaling pathway by targeting PTEN. However, very little is known about
      the relationship between hsa-miR-494-3p and EV71 infection. The overall goal of
      the study is to get a better insight into whether or not hsa-miR-494-3p is
      involved in the EV71 infection. We found that the EV71 infection induces cellular
      apoptosis, and that this process can be counteracted by the over-expression of
      hsa-miR-494-3p mimics. We also present evidence that cell lines deficient in hsa
      miR-494-3p are more sensitive to EV71-induced cell death than the corresponding
      control cells. Collectively, these findings confirm and extend the pervious
      observation suggesting that disturbances in miRNAs expression can influence EV71
      propagation. In addition, they lend strong support to the ideas that hsa-miR-494
      3p-mediated signaling pathway plays an important role in the EV71 replication,
      and that this may have profound implications on our views on EV71-related
      diseases.

PMID- 30234022
TI  - Mobilizable Plasmids for Tunable Gene Expression in Francisella novicida.
AB  - Francisella tularensis is the causative agent of the life-threatening disease
      tularemia. However, the molecular tools to study Francisella are limited.
      Especially, expression plasmids are sparse and difficult to use, as they are
      unstable and prone to spontaneous loss. Most Francisella expression plasmids lack
      inducible promoters making it difficult to control gene expression levels. In
      addition, available expression plasmids are mainly designed for F. tularensis,
      however, genetic differences including restriction-modification systems impede
      the use of these plasmids in F. novicida, which is often used as a model organism
      to study Francisella pathogenesis. Here we report construction and
      characterization of two mobilizable plasmids (pFNMB1 and pFNMB2) designed for
      regulated gene expression in F. novicida. pFNMB plasmids contain a tetracycline
      inducible promoter to control gene expression levels and oriT for RP4 mediated
      mobilization. We show that both plasmids are stably maintained in bacteria for
      more than 40 generations over 4 days of culturing in the absence of selection
      against plasmid loss. Expression levels are dependent on anhydrotetracycline
      concentration and homogeneous in a bacterial population. pFNMB1 and pFNMB2
      plasmids differ in the sequence between promoter and translation start site and
      thus allow to reach different maximum levels of protein expression. We used
      pFNMB1 and pFNMB2 for complementation of Francisella Pathogenicity Island mutants
      DeltaiglF, DeltaiglI, and DeltaiglC in-vitro and pFNMB1 to complement DeltaiglI
      mutant in bone marrow derived macrophages.

PMID- 30234024
TI  - Autoregulation of ToxR and Its Regulatory Actions on Major Virulence Gene Loci in
      Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus, the leading causative agent of seafood-associated
      gastroenteritis, harbors two major virulence gene loci T3SS1 and Vp-PAI (T3SS2
      and tdh2). ToxR is a virulence regulator of vibrios. Cell density-dependent
      transcriptional pattern of toxR and its regulatory actions on T3SS1 and Vp-PAI
      have been previously reported, but the detailed regulatory mechanisms are still
      obscure. In the present work, we showed that the highest transcription level of
      toxR occurs at an OD600 = 0.2-0.4, which may be due to the subtle repression of
      ToxR and the quorum-sensing (QS) master regulator AphA. We also showed that ToxR
      is involved in regulating the mouse lethality, enterotoxicity, cytotoxicity, and
      hemolytic activity of V. parahaemolyticus. ToxR binds to the multiple promoter
      proximal DNA regions within the T3SS1 locus to repress their transcription. In
      addition, ToxR occupies the multiple promoter-proximal DNA regions of Vp-PAI
      locus to activate their transcription. Thus, ToxR regulates the multiple
      virulence phenotypes via directly acting on the T3SS1 and Vp-PAI genes. Data
      presented here provide a deeper understanding of the regulatory patterns of ToxR
      in V. parahaemolyticus.

PMID- 30234023
TI  - Promising Antifungal Targets Against Candida albicans Based on Ion Homeostasis.
AB  - In recent decades, invasive fungal infections have been increasing significantly,
      contributing to high incidences and mortality in immunosuppressed patients.
      Candida albicans (C. albicans) is the most prevalent opportunistic fungal
      pathogen in humans that can cause severe and often fatal bloodstream infections.
      Current antifungal agents have several limitations, including that only a small
      number of classes of antifungals are available, certain of which have severe
      toxicity and high cost. Moreover, the emergence of drug resistance is a new
      limitation to successful patient outcomes. Therefore, the development of
      antifungals with novel targets is an essential strategy for the efficient
      management of C. albicans infections. It is widely recognized that ion
      homeostasis is crucial for all living cells. Many studies have identified that
      ion-signaling and transduction networks are central to fungal survival by
      regulating gene expression, morphological transition, host invasion, stress
      response, and drug resistance. Dysregulation of ion homeostasis rapidly mediates
      cell death, forming the mechanistic basis of a growing number of compounds that
      elicit antifungal activity. Most of the potent antifungals have been widely used
      in the clinic, and certain of them have low toxicity, meaning that they may be
      expected to be used as antifungal drugs in the future. Hence, we briefly
      summarize the homeostasis regulation of several important ions, potential
      antifungal targets based on these ion-signaling networks, and antifungal
      compounds based on the disruption of ion homeostasis. This summary will help in
      designing effective drugs and identifying new targets for combating fungal
      diseases.

PMID- 30234025
TI  - Virtual Screening and Biomolecular Interactions of CviR-Based Quorum Sensing
      Inhibitors Against Chromobacterium violaceum.
AB  - The rise of bacterial multi drug resistance becomes a global threat to the
      mankind. Therefore it is essential to find out alternate strategies to fight
      against these "super bugs." Quorum sensing (QS) is a cell-to-cell communication
      mechanism by which many bacteria regulate their biofilm and virulence factors
      expression to execute their pathogenesis. Hence, interfering the quorum sensing
      is an effective alternate strategy against various pathogens. In this study, we
      aimed to find out potential CviR-mediated quorum sensing inhibitors (QSIs)
      against Chromobacterium violaceum. Virtual screening from a natural products
      database, in vitro biofilm and violacein inhibition assays have been performed.
      Biofilm formation was investigated using confocal microscopy and gene expression
      studies were carried out using qRT-PCR. Further, to study the biomolecular
      interaction of QSIs with purified CviR Protein (a LuxR homologue), microscale
      thermophoresis (MST) analysis was performed. Results suggested that
      phytochemicals SPL, BN1, BN2, and C7X have potential GScore when compared to
      cognate ligand and reduced the biofilm formation and violacein production
      significantly. Especially, 100 MUM of BN1 drastically reduced the biofilm
      formation about 82.61%. qRT-PCR studies revealed that cviI, cviR, vioB, vioC,
      vioD genes were significantly down regulated by QSIs. MST analysis confirmed the
      molecular interactions between QSIs and purified CviR protein which cohere with
      the docking results. Interestingly, we found that BN2 has better interaction with
      CviR (Kd = 45.07 +/-1.90 nm). Overall results suggested that QSIs can potentially
      interact with CviR and inhibit the QS in a dose dependent manner. Since, LuxR
      homologs present in more than 100 bacterial species, these QSIs may be developed
      as broad spectrum anti-infective drugs in future.

PMID- 30234026
TI  - The Role of Mammalian Reservoir Hosts in Tick-Borne Flavivirus Biology.
AB  - Small-to-medium sized mammals and large animals are lucrative sources of blood
      meals for ixodid ticks that transmit life-threatening tick-borne flaviviruses
      (TBFVs). TBFVs have been isolated from various organs obtained from wild-caught
      Myodes and Apodemus species in Europe and Asia. Thus, these rodents are well
      established reservoirs of TBFVs. Wild-caught Peromyscus species have demonstrated
      seropositivity against Powassan virus, the only TBFV known to circulate in North
      America, suggesting that they may play an important role in the biology of the
      virus in this geographic region. However, virus isolation from Peromyscus species
      is yet to be demonstrated. Wild-caught medium-sized mammals, such as woodchucks
      (Marmota monax) and skunks (Mephitis mephitis) have also demonstrated
      seropositivity against POWV, and virus was isolated from apparently healthy
      animals. Despite the well-established knowledge that small-to-medium sized
      animals are TBFV reservoirs, specific molecular biology addressing host-pathogen
      interactions remains poorly understood. Elucidating these interactions will be
      critical for gaining insight into the mechanism(s) of viral pathogenesis and/or
      resistance.

PMID- 30234027
TI  - Comparison of Fecal Collection Methods for Microbiome and Metabolomics Studies.
AB  - Background: Integrated microbiome and metabolomics analyses hold the potential to
      reveal interactions between host and microbiota in relation to disease risks.
      However, there are few studies evaluating how field methods influence fecal
      microbiome characterization and metabolomics profiling. Methods: Five fecal
      collection methods [immediate freezing at -20 degrees C without preservative,
      OMNIgene GUT, 95% ethanol, RNAlater, and Flinders Technology Associates (FTA)
      cards] were used to collect 40 fecal samples from eight healthy volunteers. We
      performed gut microbiota 16S rRNA sequencing, untargeted metabolomics profiling,
      and targeted metabolomics focusing on short chained fatty acids (SCFAs). Metrics
      included alpha-diversity and beta-diversity as well as distributions of
      predominant phyla. To evaluate the concordance with the "gold standard" immediate
      freezing, the intraclass correlation coefficients (ICCs) for alternate fecal
      collection systems were calculated. Correlations between SCFAs and gut microbiota
      were also examined. Results: The FTA cards had the highest ICCs compared to the
      immediate freezing method for alpha-diversity indices (ICCs = 0.96, 0.96, 0.76
      for Shannon index, Simpson's Index, Chao-1 Index, respectively), followed by
      OMNIgene GUT, RNAlater, and 95% ethanol. High ICCs (all >0.88) were observed for
      all methods for the beta-diversity metric. For untargeted metabolomics, in
      comparison to immediate freezing which detected 621 metabolites at >=75%
      detectability level, 95% ethanol showed the largest overlapping set of
      metabolites (n = 430; 69.2%), followed by FTA cards (n = 330; 53.1%) and OMNIgene
      GUT (n = 213; 34.3%). Both OMNIgene GUT (ICCs = 0.82, 0.93, 0.64) and FTA cards
      (ICCs = 0.87, 0.85, 0.54) had acceptable ICCs for the top three predominant SCFAs
      (butyric acid, propionic acid and acetic acid). Nominally significant
      correlations between bacterial genera and SCFAs (P < 0.05) were observed in fecal
      samples collected by different methods. Of note, a high correlation between the
      genus Blautia (known butyrate producer) and butyric acid was observed for both
      immediate freezing (r = 0.83) and FTA cards (r = 0.74). Conclusions: Four
      alternative fecal collection methods are generally comparable with immediate
      freezing, but there are differences in certain measures of the gut microbiome and
      fecal metabolome across methods. Choice of method depends on the research
      interests, simplicity of fecal collection procedures and ease of transportation
      to the lab, especially for large epidemiological studies.

PMID- 30234028
TI  - Newcastle Disease Virus V Protein Inhibits Cell Apoptosis and Promotes Viral
      Replication by Targeting CacyBP/SIP.
AB  - Newcastle disease virus (NDV) has been classified by the World Organization for
      Animal Health (OIE) as a notable disease-causing virus, and this virus has the
      ability to infect a wide range of birds. V protein is a non-structural protein of
      NDV. V protein has been reported to inhibit cell apoptosis (Park et al., 2003a)
      and promote viral replication (Huang et al., 2003), however, the mechanisms of
      action of V protein have not been elucidated. In the present study, a yeast two
      hybrid screen was performed, and V protein was found to interact with the
      CacyBP/SIP protein. The results of co-immunoprecipitation and immuno
      colocalization assays confirmed the interaction between V protein and CacyBP/SIP.
      The results of quantitative-PCR and viral plaque assays showed that
      overexpression of CacyBP/SIP inhibited viral replication in DF-1 cells.
      Overexpression of CacyBP/SIP in DF-1 cells induced caspase3-dependent apoptosis.
      The effect of knocking down CacyBP/SIP by siRNA was the opposite of that observed
      upon overexpression. Moreover, it is known that NDV induces cell apoptosis via
      multiple caspase-dependent pathways. Furthermore, V protein inhibited cell
      apoptosis and downregulated CacyBP/SIP expression in DF-1 cells. Taken together,
      the findings of the current study indicate that V protein interacts with
      CacyBP/SIP, thereby regulating cell apoptosis and viral replication.

PMID- 30234030
TI  - Systemic Candidiasis and TLR2 Agonist Exposure Impact the Antifungal Response of
      Hematopoietic Stem and Progenitor Cells.
AB  - We have previously demonstrated that Candida albicans induces differentiation of
      hematopoietic stem and progenitor cells (HSPCs) toward the myeloid lineage both
      in vitro and in vivo in a TLR2- and Dectin-1-dependent manner, giving rise to
      functional macrophages. In this work, we used an ex vivo model to investigate the
      functional consequences for macrophages derived from HSPCs in vivo-exposed to
      Pam3CSK4 (a TLR2 agonist) or C. albicans infection. Short in vivo treatment of
      mice with Pam3CSK4 results in a tolerized phenotype of ex vivo HSPC-derived
      macrophages, whereas an extended Pam3CSK4 treatment confers a trained phenotype.
      Early during candidiasis, HSPCs give rise to macrophages trained in their
      response to Pam3CSK4 and with an increased fungicidal activity; however, as the
      infection progresses to higher fungal burden, HSPC-derived macrophages become
      tolerized, while their fungicidal capacity is maintained. These results
      demonstrate that memory-like innate immune responses, already described for
      monocytes and macrophages, also take place in HSPCs. Interestingly, extended
      Pam3CSK4 treatment leads to an expansion of spleen HSPCs and myeloid cells, and
      drastically reduces the fungal burden in the kidney and spleen during systemic C.
      albicans infection. This protection against tissue invasion is abrogated by
      immunodepletion of HSPCs, suggesting their protective role against infection in
      this model. In addition, HSPCs produce in vitro cytokines and chemokines in
      response to C. albicans and Pam3CSK4, and these secretomes are capable of
      inducing myeloid differentiation of HSPCs and modulating peritoneal macrophage
      cytokine responses. Taken together, these data assign an active role for HSPCs in
      sensing pathogens during infection and in contributing to host protection by
      diverse mechanisms.

PMID- 30234032
TI  - The Delhi Declaration 2018: "Healthcare for All Rural People" - Alma Ata
      Revisited.
AB  - In the 40th anniversary year of Alma Ata: Health for All by 2000 conference,
      Academy of Family Physicians of India organized the 15th WONCA World Rural Health
      conference in New Delhi from 26 to 29th April 2018. More than a thousand
      delegates (1044) from 40 countries participated in this international conference.
      The conference attracted a multidisciplinary participation from various
      backgrounds with an interest in rural primary healthcare. Theme of this
      conference was "Healing the Heart of Healthcare-Leaving No one behind". The
      conference aspired to bring rural healthcare on global agenda. This was the first
      ever World Rural Health Conference organized in South Asia, incidentally a
      quarter of human population lives in South Asia, majority of which is based in
      rural habitat. The conference culminated with the unanimous adoption of the Delhi
      Declaration; calling for people living in rural and isolated parts of the to be
      given special priority, if nations are to achieve universal health coverage. The
      declaration has been cited at the website of the World Health Organization and is
      available in six languages (Chinese, English, French, Japanese, Portuguese, and
      Spanish.

PMID- 30234033
TI  - A study on cervical cancer screening in asymptomatic women using Papanicolaou
      smear in a tertiary care hospital in an urban area of Mumbai, India.
AB  - Introduction: Cervical cancer is the most common cause of death among women in
      developing countries. Among the Indian women, cervical cancer is the most common
      genital tract cancer. Papanicolaou (Pap) smear test plays a vital role in the
      detection of cervical cancer even in its premalignant condition. The aim of this
      study to evaluate the role of Pap smear in detecting premalignant and malignant
      lesions as well as nonneoplastic lesions of the cervix and to determine the
      prevalence of various lesions. Materials and Methods: We screened 1100 women in
      the age group of 21-65 years who attended our medical camp organized by the
      hospital in outdoor patient department. All women was willing to give consent for
      screening by Pap smear test were included. Results: Of 1100 cases, majority of
      the cases were benign comprising negative for intraepithelial neoplasia (NILM) of
      about 581 (52.8%) cases, 203 (18.4%) inflammatory, atypical squamous cells of
      undetermined significance 45 (4%), low-grade squamous intraepithelial lesion
      (LSIL) in 75 (6.8%), and high-grade squamous intraepithelial lesion (HSIL) in 74
      (6%) women. Overall sensitivity and specificity for the detection of LSIL were
      75.8% and 94.6% and those for the detection of HSIL were 68.9% and 98.6%.
      Conclusions: Pap smear test is a very easy, noninvasive, useful, simple, safe,
      and very economical tool to detect preinvasive cervical epithelial lesions. It is
      evident and proven that every woman above the age of 30-35 years must be
      subjected to cervical screening and this must be continued even in the
      postmenopausal period.

PMID- 30234031
TI  - Intracranial Inoculation Is More Potent Than Intranasal Inoculation for Inducing
      Optic Neuritis in the Mouse Hepatitis Virus-Induced Model of Multiple Sclerosis.
AB  - Neurotropic strains of mouse hepatitis virus (MHV) induce acute inflammation and
      chronic demyelination in the spinal cord and optic nerves mediated by axonal
      spread following intracranial inoculation in mice, with pathologic features
      similar to the human demyelinating disease multiple sclerosis. Spinal cord
      demyelination is also induced following intranasal inoculation with neurotropic
      MHV strains, however much higher viral doses are required as compared to
      intracranial inoculation. Recently, it was shown that intranasal administration
      of low concentrations of proteins leads to significant, rapid accumulation of
      protein in the optic nerve and in the eye, with only low levels reaching spinal
      cord and other brain regions. Thus, we examined whether intranasal inoculation
      with MHV at doses equivalent to those given intracranially could induce optic
      neuritis-inflammation, demyelination and loss of retinal ganglion cells (RGCs) in
      the optic nerve with or without inducing spinal cord demyelination. Four week old
      male C57BL/6J mice were inoculated intracranially with the recombinant
      demyelinating strain RSA59, or intranasally with RSA59 or the non-demyelinating
      strain RSMHV2 as control. One month post-inoculation, mice inoculated
      intracranially with RSA59 had significant myelin loss in both spinal cord and
      optic nerves, with significant loss of RGCs as well, consistent with prior
      studies. As expected, intranasal inoculation with RSA59 failed to induce
      demyelination in spinal cord; however, it also did not induce optic nerve
      demyelination. No acute inflammation was found, and no viral antigen was
      detected, in the optic nerve or retina 1 day after inoculation. Results confirm
      the neurotropic effects of RSA59 following intracranial inoculation, and suggest
      that direct infection with axonal transport of virus from brain to spinal cord
      and optic nerve is required to induce demyelinating disease. These studies
      suggest that MHV does not selectively concentrate in optic nerve and retina to
      sufficient levels to induce demyelination following intranasal inoculation.
      Intracranial inoculation should continue to be considered a preferred method for
      studies of MHV-induced optic neuritis and central nervous system (CNS)
      demyelinating disease.

PMID- 30234029
TI  - Micromanaging Immunity in the Murine Host vs. the Mosquito Vector: Microbiota
      Dependent Immune Responses to Intestinal Parasites.
AB  - The digestive tract plays a central role in nutrient acquisition and harbors a
      vast and intricate community of bacteria, fungi, viruses and parasites,
      collectively known as the microbiota. In recent years, there has been increasing
      recognition of the complex and highly contextual involvement of this microbiota
      in the induction and education of host innate and adaptive immune responses under
      homeostasis, during infection and inflammation. The gut passage and colonization
      by unicellular and multicellular parasite species present an immense challenge to
      the host immune system and to the microbial communities that provide vital
      support for its proper functioning. In mammals, parasitic nematodes induce
      distinct shifts in the intestinal microbial composition. Vice versa, the
      commensal microbiota has been shown to serve as a molecular adjuvant and
      immunomodulator during intestinal parasite infections. Moreover, similar
      interactions occur within insect vectors of deadly human pathogens. The gut
      microbiota has emerged as a crucial factor affecting vector competence in
      Anopheles mosquitoes, where it modulates outcomes of infections with malaria
      parasites. In this review, we discuss currently known involvements of the host
      microbiota in the instruction, support or suppression of host immune responses to
      gastrointestinal nematodes and protozoan parasites in mice, as well as in the
      malaria mosquito vector. A deeper understanding of the mechanisms underlying
      microbiota-dependent modulation of host and vector immunity against parasites in
      mammals and mosquitoes is key to a better understanding of the host-parasite
      relationships and the identification of more efficient approaches for
      intervention and treatment of parasite infections of both clinical and veterinary
      importance.

PMID- 30234034
TI  - Patients satisfaction with consultation at primary health care centers in Abha
      City, Saudi Arabia.
AB  - Aim of Study: This study aims to assess patients satisfaction regarding
      consultations at the General Clinics of primary health-care (PHC) centers, in
      Abha City. Patients and Methods: This cross-sectional study design was conduct
      among adult patients attending training PHC centers in Abha City, Saudi Arabia
      during September 2016. The researcher designed a data collection sheet that
      comprised patients' personal characteristics and the consultation satisfaction
      questionnaire, which contained 18 questions within four dimensions, i.e., general
      satisfaction; professional care; depth of relationship; and length of
      consultation. Results: The total number of the patient included in this study was
      400, more than half of them were male (54%). Most of them were Saudi (90%),
      married (79%), and educated (93%). More than half 53% were dissatisfied, 20% were
      satisfied with consultation while 27% were natural. The most important factor
      affecting satisfaction with consultation was age, education level and income.
      Conclusions: Patients satisfaction toward their consultation experience at
      general clinics of training PHC centers in Abha City was suboptimal. Total
      consultation scores differ significantly according to their age groups, education
      level, and monthly income. Recommendations: PHC physicians should be more
      concerned with improving medical consultations provided to their patients.
      Continuing medical education and training of PHC physicians about provision of
      medical consultation.

PMID- 30234035
TI  - Poliomyelitis era in Trinidad from 1940 to 1972 and beyond: Implications for
      effective global health governance for its eradication.
AB  - Background: Acute poliomyelitis (APM/polio) is a viral infection caused by the
      polio virus that continues to have a fascinating social and economic impact on
      countries throughout the world. Humans acquire the virus by close personal
      contact with transmission occurring through the fecal-oral route. The majority of
      poliovirus infections results in no illness or produces only self-limited
      symptoms, however in approximately 5% of infected patients flaccid paralysis of
      the limbs can occur and 1% can die. Although APM is no longer a feared disease
      mainly due to the development of effective vaccines, its eradication remains
      elusive. Methods: The aim of this study is to review the historical impact of APM
      in Trinidad. A retrospective analysis of all cases occurring from 1939 to 1972
      was undertaken. Data for the study were derived from two sources the Annual
      Statistical Reports of the Ministry of Health 1972-2000 and the epidemiological
      publications of the League of Nations Health Organization and the World Health
      Organization. Results: There were four outbreaks of APM in Trinidad 1941, 1942,
      1954, and 1972. After the final outbreak in 1972, APM was eradicated not only
      from Trinidad but also all the countries of the Americas mainly through the
      effective use of the oral polio vaccine. Conclusion: Polio has brought together
      international agencies, governments, and the people to build an effective public
      health system around a common vision for health and wellbeing. The polio
      eradication and endgame strategic plan represents a major milestone in polio
      eradication developed by global polio eradication initiative. The initiative
      would still benefit from adopting some of the best practices in governance from
      other organizations in the global health sector.

PMID- 30234036
TI  - Determinants of wasting among schoolchildren in a Southwestern state of Nigeria:
      Implications to strengthen the nutritional component of primary health-care
      model.
AB  - Background: Wasting is linked to about one-third of mortality among school-age
      children. More studies have centered on stunting among under-five children, with
      few documented studies exploring comparability and determinants of wasting among
      school pupils in southwestern Nigeria. This study aimed to investigate the
      comparability and determinants of wasting among schoolchildren in rural and urban
      communities of Obafemi-Owode local government area, Ogun State, Nigeria. Methods:
      A cross-sectional study utilizing a quantitative approach was carried out among
      children both in rural and urban primary schools. Data were collected through
      interviewer-administered questionnaires. EPI-INFO version 6.03 was used, children
      were classified as wasted if weight-for-height Z-scores were <2 standard
      deviations below the National Center for Health Statistics/World Health
      Organization median. Associations were tested using t-tests and Chi-square test,
      while predictors were examined with logistic regression at 95% level of
      significance. Results: Male gender was predominant (54.6%). Significantly more
      pupils from rural areas lived with grandparents and other guardians (60.3%)
      compared to their urban counterparts (39.7% P = 0.005). Pupils from rural schools
      were four times more likely to be wasted compared to those located in urban
      regions (odds ratio [OR]: 4.2; 95 confidence interval [CI] = 2.24-7.69). Male
      pupils were twice likely to be wasted compared to the female pupils (OR: 2.08; 95
      CI = 1.22-3.55). Conclusion: Conclusively, the study revealed that the prevalence
      of wasting was higher among children from rural schools than in urban schools.
      There is an urgent need to implement viable interventions and policies that
      address nutritional deficiencies in primary school pupils, particularly in rural
      areas.

PMID- 30234037
TI  - The mental health needs of women in natural disasters: A qualitative study with a
      preventive approach.
AB  - Context: Considering the importance of psychological issues during disasters and
      the key role of women in the family and society, a preventive approach toward
      mental health improvement in women is of great importance. Aims: This study aimed
      to identify the mental health needs of women in natural disasters through a
      preventive approach. Settings and Design: The present qualitative study was
      conducted through content analysis method and semi-structured interviews with 40
      specialists and seven women who had experienced natural disasters. The study
      participants were selected through snowball and purposive sampling. Subjects and
      Methods: A heterogeneous sample was selected. To ensure the reliability and
      verifiability of data, the texts of the interviews were approved by each
      interviewee. Statistical Analysis Used: Thematic analysis was used to report
      findings. Results: In this study, two themes, seven main categories, and 21
      subcategories and secondary codes were extracted. The themes were internal
      physical (biological) and external environmental (social, political and legal
      measures, cultural and spiritual measures, psychology, and lifestyle) factors.
      Conclusions: The dimensions related to the mental health of women are
      multifactorial and beyond only psychological variables. The improvement of the
      mental health of women can be achieved through aggregation of perspectives in
      different organizational, governmental, and political areas in collaboration
      within the society with a healthy gender perspective free of discrimination,
      inequality, and injustice.

PMID- 30234038
TI  - Managerial dynamics influencing doctor-nurse conflicts in two Nigerian hospitals.
AB  - Background: In the hospital, authority does not usually comes from a single
      person nor is it exercised in a single chain of command as is obtainable in most
      formal organizations. Doctors exercise substantial authority within the
      organizational structure of the hospital and therefore enjoy high autonomy in the
      hospital setting. This nature of autonomy within the medical and its allied
      professions has the propensity to incite conflicts within the hospital settings.
      The study thus sought to examine how the relationship of authority and influence
      between doctors and nurses within the hospital organization generates conflicts
      and to evaluate the effectiveness of managerial procedures utilized to resolve
      doctor-nurse conflict in the selected hospitals. Methods: Semi-structured
      questionnaires were self-administered to 323 health workers who were sampled from
      one secondary and the only one tertiary hospital in the state at the time. Focus
      group discussions (FGDs) were conducted with three groups each of doctors and
      nurses in the selected hospitals. The organograms of both organizations were also
      reviewed to evaluate structural relationships of authority between doctors and
      nurses. Data were analyzed using unadjusted odd ratios at 95% level of
      significance. Results: Respondents were also twice likely to attest that the
      command structure and its ability to resolve conflicts was below average in
      assessment (odds ratio [OR] - 2.05; 95% confidence interval [CI] - 1.27-3.29).
      Undue advantage (partisan approach) for a particular group by management to
      conflict resolution was thrice likely to be practiced in both hospitals but more
      in state hospital compared to the federal medical center (OR - 2.93; 95% CI -
      1.54-5.58). Some findings from respondents in the FGDs revealed lackadaisical
      approach by the management in tackling conflicts among health workers.
      Conclusion: Doctor-nurse conflict is caused by several organizational and
      managerial factors. Hospital management must understand the interplay of these
      factors and institute appropriate managerial policies to tackle the problem
      appropriately.

PMID- 30234039
TI  - A study to assess the knowledge, attitude, and practices about blood donation
      among medical students of a medical college in North India.
AB  - Introduction: Scarcity of blood and blood products is frequently encountered in
      health care institutions. Medical students can serve as an important pool of
      potential blood donors for the attached teaching hospitals. Aim: To determine the
      knowledge, attitude and practices (KAP) of medical students about voluntary blood
      donation. Settings and Design: It was a cross- sectional study conducted among
      medical students of Dr RPGMC Tanda in Himachal Pradesh, in the months of August
      to December, 2015. Material and Methods: All the students present on the day of
      the survey who expressed their consent for participation were enrolled in the
      study. A pre- tested, structured questionnaire was used as a study tool. After
      the collection of the baseline information, a brief interactive awareness
      session, addressing voluntary blood donation was organized for the participants
      and their willingness to donate blood was again noted at the conclusion of the
      session. The data was analyzed by using SPSS software. Results: 235 students
      participated in the study, 102 (43.4%) males and 133 (56.5%) females. The mean
      age was 20.42 +/-1.38 years. Knowledge of Voluntary Blood Donation: The mean
      knowledge score of participants was 74.4%. Overall 225 (95.7%) participants were
      aware of their blood groups. Attitude related to blood donation: 91% study
      participants felt that people should donate blood and were themselves willing to
      donate blood. Practice Relating to Blood Donation: Out of the 235 study
      participants, only 54(22.9%) had donated blood so far. Willingness to donate
      blood after interactive awareness session increased from 91% to 97.5%.
      Conclusion: The study population has relatively good knowledge and a favourable
      attitude about voluntary blood donation. However the prevalence of blood donation
      among the students is still low, especially among the girls.

PMID- 30234040
TI  - A study on menstruation of Indian adolescent girls in an urban area of South
      India.
AB  - Background: Menstrual cycle is an important indicator of women's reproductive
      health. However, menstruation has a different pattern within a few years after
      menarche, which might not be well understood by many adolescent girls. Materials
      and Methods: A cross-sectional study was conducted on 536 healthy menstruating
      females aged 10-19 years. Standardized self-reporting questionnaires were used to
      obtain relevant data. The categorical data were analyzed using Chi-square or
      Fisher's exact test. Results: Mean age of menarche was 13 +/- 1.1 years with wide
      variations, i.e., 10-17 years. 73.1% had cycle duration of 21-35 days. More than
      half of them reported 5-6 days' duration of menstrual blood flow and 12% of the
      participants had >7 days of flow. Long blood flow duration was more prevalent in
      early than in late adolescence. 30.1% reported abundant blood loss. 66.8% had
      dysmenorrhea and no difference was observed between early and late adolescents.
      Menstrual cycles tend to be shorter in early adolescence period. Conclusion: A
      comprehensive school education program on menarche and menstrual problems may
      help girls to cope better and seek proper medical assistance.

PMID- 30234041
TI  - Utilization of institutional rehabilitation service in pediatric patients with
      disability in Southwest Rajasthan.
AB  - Background: Rehabilitating disabled child maximizes functional independence,
      thereby, enhancing the quality of life and better community participation.
      Utilization of rehabilitation services is a significant issue in developing
      countries like India. This study aims to observe the pattern of utilization of
      institutional rehabilitation services by pediatric patients with disability.
      Methods: This was an observational study (descriptive cross-sectional study)
      conducted at Department of Physical Medicine and Rehabilitation in a tertiary
      care set-up. Descriptive data from an ongoing study involving children with and
      without developmental delay (DD) over 1 year were collected in terms of age,
      gender, distance from the institute, diagnosis, and frequency of visit.
      Utilization pattern for rehabilitation services among pediatric patients was
      analyzed with respect to diagnosis and frequency of visit under each diagnosed
      category. The demographic variable of age, gender, and distance from the
      institute was further correlated to frequency of visit. IBM SPSS statistics 22
      was used for descriptive statistical analysis and correlation of variables.
      Results: Of 464 disabled children using rehabilitation service, data for 399 (M:
      255, F: 144) children were complete with age ranging from 3 months to 18 years
      and distance from 1 km to 600 km from institute. There were 330 children with DD
      and 69 in non-DD category. Two hundred and sixty-eight cases used one-time
      consultancy, 86 preferred intermittent services, and 45 patients were regular.
      Negligible correlation with a trend toward negative values was observed between
      frequency of service utilization and distance (Rho = -0.139 Sig. = 0.006, at 0.01
      level) and between age and utilization frequency (Rho = -0.074, Sig = 0.140).
      Conclusions: The study showed that children with DD were main utilizers of
      rehabilitation services. Nearly 67% of disabled children utilized services only
      once with a trend toward younger age group and those nearer to institute were
      noted.

PMID- 30234042
TI  - Prevalence of metabolic syndrome and associated risk factors among geriatric
      population living in a high altitude region of rural Uttarakhand, India.
AB  - Introduction: Metabolic syndrome (MetS) is responsible for 2.5-fold increase in
      cardiovascular mortality and a 5-fold higher risk of developing diabetes.
      Materials and Methods: A community-based cross-sectional study was conducted
      during 2015-2016 in District Nainital. A list of all villages was developed. From
      this list, thirty villages were identified using population proportionate to size
      sampling method. From each village, thirty geriatric subjects (GSs) were
      selected. The study population included 979 GSs aged 60 years and above. The data
      were collected on anthropometry, blood pressure, blood glucose, and lipid profile
      from all the enrolled subjects. The prevalence of MetS was estimated using
      International Diabetes Federation criteria. Univariate and multivariate analysis
      was done to identify factors associated with MetS. Results: The prevalence of
      MetS was found to be 28.6%. Step-wise multivariate logistic regression analysis
      found that female gender, higher income, and body mass index >=25 were
      significant and independent risk factors of MetS amongst GP. Conclusion: There is
      a need for screening of GP living in high altitude region so that efforts can be
      initiated to prevent complications of MetS.

PMID- 30234043
TI  - Nursing students: A vulnerable health-care worker for needlesticks injuries in
      teaching hospitals.
AB  - Background: Occupational exposure to bloodborne pathogen is a significant risk to
      health-care workers. In any teaching hospital apart from regular health-care
      workers and employees, there are significant population of students and trainee.
      It is important to assess the health-care worker in hospital which has maximum
      chances of exposure to these pathogens. The aim of this study is to determine the
      most susceptible job group for needlestick injury (NSI) reported in a newly
      established teaching medical institute in the Western part of Rajasthan, India.
      Methods: This is a retrospective analysis of data of NSI occurred during
      September 2014 to January 2017. Results: Sixty three NSIs were reported during
      the study. Nursing students were the most vulnerable group who reported maximum
      number of NSI. Among the nursing students, 72% were completely vaccinated against
      hepatitis B virus. Conclusions: Nursing students are at utmost risk for NSIs, the
      prevention of which requires regular training and education.

PMID- 30234044
TI  - Internet addiction and its mental health correlates among undergraduate college
      students of a university in North India.
AB  - Introduction: Internet addiction (IA) is an emerging phenomenon among the youth
      of India. It has been found to be associated with mental health problems. This
      study was therefore conducted to find out the burden of IA among college students
      in Delhi, its risk factors and association with depression, anxiety, and stress.
      Methods: A cross-sectional study was conducted, with face-to-face interviews,
      among the nonprofessional college students of the University of Delhi. Simple
      random sampling was used to select the students from the list obtained from the
      three colleges. Young's IA test scale and depression, anxiety, and stress short
      scale were used to measure IA and the mental health correlates, respectively. Chi
      square tests were applied for testing the association of IA with the
      sociodemographic variables, the variables related to internet usage patterns, and
      the mental health variables. Independent predictors were determined using
      logistic regression modeling. Results: The prevalence of IA was 25.3%. The mean
      (standard deviation) age of the participants was 19.1 (1.02) years and 62.1% were
      males. The median family income was INR 50,000. IA was significantly associated
      with higher family income, greater screen time, always online status, and greater
      duration of internet use per week. The independent predictors of IA were greater
      duration of internet use per week and always online status, depression, anxiety,
      and stress. Conclusion: The burden of IA among the college students was high.
      depression, anxiety, and stress were found to be independent predictors of IA.

PMID- 30234045
TI  - Tobacco use, exposure to second-hand smoke among pregnant women and their
      association with birth weight: A retrospective cohort study.
AB  - Background: There is paucity of studies on prevalence of SHS among pregnant women
      and its association with low birth weight (LBW). Objectives: The study was
      designed to determine the proportion of tobacco use, exposure to second hand
      smoke among pregnant women and their association with LBW. Materials and Methods:
      A Retrospective cohort study was conducted from March-June 2017 among 1043
      pregnant women admitted for delivery in the Department of Obstetrics and
      Gynecology, JIPMER. Socio-demographic and obstetric characteristics, tobacco use
      and exposure to SHS during pregnancy were assessed by interviews. Birth weight of
      the baby was also extracted. Data was analysed using STATA v12. Univariate
      analysis was used to assess the association of socio-demographic, obstetric
      characteristics and exposure to SHS with LBW. Results: Out of 1043 pregnant
      women, the mean age was 25 (+/-3.9) years. More than half (57.4%) of women were
      primigravida. The proportion of women exposed to SHS during pregnancy was 69.9%
      (95% CI: 67.0-72.6) among which 24% of the women belonged to family, where family
      members were smokers. Only four had ever used tobacco in the past. However, none
      used any form of tobacco during pregnancy. LBW was present in 21.4% of the
      babies. There was no association between exposure to SHS and LBW [PR:0.98 (95%
      CI:0.71-1.35)]. Conclusion: The study shows that there was no significant
      association between the SHS exposure of pregnant women and low birth weight.

PMID- 30234046
TI  - Prevalence of anemia among the women of childbearing age belonging to the tea
      garden community of Assam, India: A community-based study.
AB  - Background: Anemia is a condition in which the number of red blood cells becomes
      insufficient to meet the body's physiologic needs. Anemia is one of the major
      public health problems in India. The aim of this study was to find the prevalence
      and determinants of anemia among the adult females of tea garden community of
      Assam. Materials and Methods: A community-based cross-sectional study was
      conducted among 770 numbers of adult females belonging to the tea garden
      community. For all the samples, complete blood count, abnormal hemoglobin
      variants screening by high-performance liquid chromatography (HPLC), serum iron
      level, total iron binding capacity (TIBC), and serum ferritin concentrations were
      determined. Results: Out of 770 patients, 19.7% were severely anemic. Hb S and
      beta-thalassemia were the only hemoglobin types detected in the study. Hemoglobin
      type, mean corpuscular volume, TIBC, and serum ferritin level were the important
      determinants of anemia in the present study. Conclusion: To reduce the burden of
      anemia among the adult females of tea garden community, the females should be
      screened periodically, and appropriate measures should be taken.

PMID- 30234047
TI  - Factors affecting primary health-care physicians' emergency-related practice;
      Eastern Province, KSA.
AB  - Background: Being the first in-line care providers, primary health-care (PHC)
      physicians may encounter all forms of emergencies, ranging from minor complaints
      to life-threatening events. This wide variation of cases challenges the
      physicians to be competent in emergency medicine. Informative literature
      describing and assessing the factors affecting PHC physicians' emergency medical
      services (EMS)-related practice is deficient (nationally and internationally).
      The aim of this study is to assess PHC physicians' practice related to EMS, the
      factors affecting it, as well as their learning needs and preferred methods of
      continuous training in emergency medicine. Methods: All physicians working in the
      selected centers were invited to complete a self-administered questionnaire
      addressing their EMS-related practice. Moreover, physicians were invited to
      participate in face-to-face semi-structured interviews and focus group
      discussions. Results: The study revealed that 87.3% of physicians had a good
      diagnostic knowledge score while only 47.6% had a good management score.
      Nonetheless, 63.5% of physicians had a neutral attitude toward EMS. The most
      common reported emergencies encountered are bronchial asthma (86.51%), cut wounds
      (83.33%), and burns (76.19%). About 62% of participants reported that their
      greatest needs for further training were in cardiovascular and central nervous
      system emergency management, preferably by practical training in hospital
      emergency department (80%). Conclusions: Dammam PHC physicians have a good
      knowledge, neutral attitude, and fair practice concerning the emergency cases
      encountered. The majority of physicians reported their need for further hands-on
      training in emergency medicine. Settings and Design: A cross-sectional, mixed
      methods study was conducted in 13 out of 26 PHC centers of Dammam, Saudi Arabia.

PMID- 30234048
TI  - Evaluation of thyroid function in type 2 diabetes in north-eastern part of India:
      A hospital-based study.
AB  - Background: Diabetes mellitus (DM) and thyroid dysfunctions are the two most
      common endocrine disorders to come across in any clinical practice. Both thyroid
      hormones and insulin act antagonistically in metabolic pathways or cycles of
      cells. The aim of our study is to look for thyroid dysfunction in patients with
      type 2 DM and its correlation with insulin resistance (IR). Methods: A cross
      sectional study was carried out among 80 newly diagnosed type 2 diabetic
      patients. Thyroid-stimulating hormone (TSH), free triiodothyronine, free
      thyroxine, and insulin were measured in fasting serum sample. Homeostasis model
      assessment for IR was calculated as per formula. Results: Among 80 diabetic
      patients, 20 were hypothyroid, 4 were hyperthyroid, and 56 were found to be
      euthyroid. IR was found to be significantly higher in hypothyroid as compared to
      euthyroid patients. A positive association was found between TSH and IR (r =
      0.230) among hypothyroid patients though association was not significant. In
      hyperthyroid patients, a strong negative correlation (r = -0.94933) was found
      between TSH and IR, but no association was found among euthyroid patients.
      Conclusion: The inability to recognize the presence of thyroid hormone
      dysfunction may be one of the important causes of poor management of type 2 DM.
      Therefore, there is a need for routine assay of thyroid hormones in type 2
      diabetic patients to improve the medical management as well as to reduce the
      morbidity in them.

PMID- 30234049
TI  - Knowledge and attitude of mandatory infectious disease notification among final
      year medical students.
AB  - Background: Disease surveillance is one of the major components to combat against
      infectious diseases. As health-care professionals are indispensable to mandatory
      notifiable disease surveillance, their knowledge and attitudes toward infectious
      disease notification played an important role for timely and effective reporting
      to the surveillance system. Therefore, we aimed to determine the knowledge of
      mandatory notifiable infectious diseases in Malaysia and attitude towards
      infectious disease reporting among final year medical students. Methods: A cross
      sectional study was conducted from May to June 2017 in the private medical
      college in Malaysia. Materials and Methods: We purposively selected the final
      year (semester 10) medical students and a total of 124 students participated in
      this study. We collected data using a self-administered, structured
      questionnaire. Data were analyzed using descriptive statistics, independent t
      test, and one-way analysis of variance. Results: Among the final year medical
      students, 47.5% had moderate knowledge but 4.2% had good knowledge of mandatory
      infectious disease notification. Only 3.2% of the students correctly answered all
      the notifiable diseases listed in the questionnaire. Most of the students had
      positive attitude toward communicable diseases reporting, rewards, and penalty
      for notification. There was no significant relationship between sociodemographic
      characteristics and knowledge and attitude of infectious disease notification.
      Conclusions: The majority of the final year medical students had moderate level
      of knowledge and positive attitude of infectious disease notification; however,
      there were some deficiencies. Better instruction and training on infectious
      disease notification procedures of Malaysia should be provided to the final year
      medical students which could not only reduce underreporting but also improve
      timely and effective reporting in future.

PMID- 30234050
TI  - Effect of intravenous iron sucrose on hemoglobin level, when administered in a
      standard-dose, to anemic pregnant women in rural Northern India.
AB  - Introduction: To combat anemia among pregnant women, in Haryana, Northern India,
      administration of intravenous iron sucrose (IVIS) was initiated in 2014 as a
      public-health measure. We assessed the effect of IVIS on hemoglobin (Hb) levels
      among the pregnant anemic women. Methods: Pregnant women identified as moderately
      or severely anemic (Hb <10.0 g/dL) in the second or third trimester during
      routine antenatal care were prescribed IVIS in a standard-dose of 400 mg given as
      100 mg on alternate days. Neither dose calculation, nor allowance for iron-store,
      was included in this study. We analyzed the data collected between June 2014 and
      December 2015, at the two primary-health-centers, on Hb level (by HemoCue method)
      before start of the therapy (baseline), and 4-week or more after the last
      infusion (endline). Results: A total of 990 women received IVIS. Both baseline
      and endline Hg-levels were available for 763 (77%), who were included in the
      analysis. At baseline, the proportion of moderate and severe anemia was 87.94%
      and 12.06%, respectively. Mean (standard deviation)-Hb increased from 7.85 g/dL
      (0.80) at baseline, to 9.62 g/dL (1.30) at endline, with a mean increase of 1.76
      g/dL (95% confidence interval 1.67, 1.85). The mean increase in Hb-level for
      pregnant women who had severe and moderate anemia at baseline was 2.54 g/dL and
      1.65 g/dL, respectively. Overall, 15.33% of women achieved normal Hb-level by the
      time of endline measurement. No serious adverse reactions were reported during
      the observation period. Conclusion: Mean increase in Hb-level was 1.76 mg/dL.
      Severely anemic pregnant women had larger increase in Hb-level when compared with
      pregnant women with moderate anemia.

PMID- 30234051
TI  - Dysmenorrhea, associated symptoms, and management among students at King Khalid
      University, Saudi Arabia: An exploratory study.
AB  - Background: Dysmenorrhoea is a common health problem among females in their
      reproductive years. Available information on dysmenorrhoea in university student
      in abah, Saudi Arabia is limited. The objective of the study was to assess the
      prevalence of dysmenorrhea and associated menstrual symptoms and their self
      management techniques among female university students of King Khalid University
      (KKU). Methods: This cross-sectional study was conducted at College of health
      science in KKU, Saudi Arabia. Sample: A total of 197 students aged between 18 and
      23 years. A Self-administrated questionnaire was used to collect data. Results:
      Dysmenorrhea was reported by more than two-thirds of the girls (70.6%). In the
      139 girls, who reported dysmenorrhea, its related information on severity of
      pain, medication use, and care-seeking behavior is detailed in the table. Severe
      pain was reported by (35.2%) respondents. Two-third of the respondents (66%)
      reported using medications for pain relief and use of herbal medicine was also
      found to be quite prevalent (69.1%). The gastrointestinal problems were the most
      common symptoms experienced by the students and were significantly high among the
      dysmenorrheal students. Less than one in four respondents (23%) reported
      consulting a doctor for their dysmenorrheal while most of them consulted with
      friends and family. Conclusion: Dysmenorrhea is a very common problem among the
      university students. A number of symptoms were related with dysmenorrhea. Even
      though it is common, and may not have a pathological cause, few students seek
      medical advice. Increasing the awareness can help in relieving the burden of this
      common health problem.

PMID- 30234052
TI  - Relationship of physical activity with body image, self esteem sedentary
      lifestyle, body mass index and eating attitude in adolescents: A cross-sectional
      observational study.
AB  - Aim: To Study Relationship of physical activity (PA) with body image, self
      esteem, body mass index (BMI), sedentary lifestyle and eating attitude in
      adolescents. Methods: An observational cross-sectional study done at the Centre
      for Adolescent Health, Kalawati Saran Children Hospital, Lady Hardinge Medical
      College, New Delhi, India. Volunteering adolescents between the age group of 13
      and 18 years were included and assessed using PA questionnaire for adolescents
      Score, Body Shape Questionnaire-34 Score, Rosenberg self esteem Score, adolescent
      sedentary activity questionnaire score, eating attitude test (EAT-26) and BMI Z
      score. Relationship of these scales to various parameters was assessed using
      correlation and regression. Results: A total of 191 boys and girls were included
      in the study; 25% had underweight, 75% were normal (only 1 child had overweight
      and none had obesity). Three fourth (77%) of the children had low PA. The girls
      were relatively more inactive (83.9% girls vs. 72.1%boys). Most (90.05%) subjects
      did not have any concerns related to body image. Almost all the subjects had
      normal or high self esteem. Nearly one quarter of the subjects (23.56%) had
      disordered eating behaviours. Multiple regression found the PA is positively
      dependent on EAT 26 score and adolescent sedentary activity questionnaire (ASAQ)
      score (sedentary score) in girls, whereas in males ASAQ (sedentary score) score
      was only variable related to physical activity questionnaire for adolescents
      score (PAQ-A). Conclusion: Normal weight and underweight adolescents had minimal
      PA and despite this, almost all had normal self-esteem and body image. PA was
      significantly related to eating and sedentary behaviours.

PMID- 30234053
TI  - Impact of indian public health standards for rural health care facilities on
      national programme for control of deafness in India: The results of a cohort
      study.
AB  - Introduction: In National Programme for Prevention and Control of Deafness
      (NPPCD), the management of ear diseases of rural India is now guided by Revised
      Indian Public Health Standards (IPHS) for Rural Health Facilities for providing
      quality ear care. However, despite the IPHS existence, coverage and quality ear
      care is questionable. Moreover, this issue has not yet been studied till now in
      the Indian context. The objective of the study was to assess the role of Private
      Medical College Training Center (Rural Health Training Centre [RHTC]) in
      augmenting quality of ear care services in NPPCD at district level by adopting
      IPHS Standards. Materials and Methods: A combined retrospective and prospective
      cohort study was done at RHTC of a Medical College in West Uttar Pradesh from
      January 1, 2013, to December 31, 2017, by retrospective approach of selecting all
      ear patients (n = 3840) and prospective way of assessing the impact of IPHS for
      ear care. The semi-structured Pro forma was used in exploring the coverage and
      quality of ear care. The data were analyzed by Epi Info version 7.2. Results: Out
      of total 4817 ear, nose, and throat (ENT) patients, the majority of ear patients
      (n = 3840) were initially dissatisfied with coverage and quality of ear services
      provided by ENT specialists at RHTC. However, when IPHS exposure was given from
      July 1, 2015 to December 31, 2017, not only majority of patients were satisfied
      (n = 3110, 81%) but also ear curative treatment was significantly higher (n =
      2120, 68.1% vs. n = 130, 17.8%, odds ratio = 9.8, RR = 1.5, P < 0.00001).
      Conclusions: Adherence to IPHS in NPPCD is essential for delivering better ear
      care by RHTC through primary health-care approach.

PMID- 30234054
TI  - Correlation between the outcomes and severity of diabetic ketoacidosis: A
      retrospective pilot study.
AB  - Introduction: Diabetic ketoacidosis (DKA) is a serious acute metabolic
      complication of diabetes mellitus (DM). It is classified into mild, moderate, and
      severe based on severity as per the American Diabetes Association (ADA)
      guidelines. There are limited data on the correlation between the severity of DKA
      and its outcomes using this classification system. The aim is to study the
      correlation between the outcomes and severity of DKA in a tertiary care center in
      India. Methodology: In this retrospective pilot study, 1527 patients with DM were
      identified over a span of 3 years, of which 63 had a discharge diagnosis of DKA
      and 37 fulfilled the ADA criteria for DKA. Following inclusion details on
      clinical parameters and outcomes of patients with mild, moderate, and severe DKA
      were compared. Results: Mild, moderate, and severe DKA accounted for 8%, 41%, and
      51% of the patients, respectively. Intensive Care Unit (ICU) care was required in
      6.7% and 47.4% of those with moderate and severe DKA, respectively. Invasive
      ventilation (IV) was required in 47% (9) of those with severe DKA only. The
      mortality rates were 13.3% and 26% among those with moderate and severe DKA. The
      mean expenditure was ?29,000, ?30,000, and ?64,000 among those with mild,
      moderate, and severe DKA, respectively. Conclusions: The ADA classification of
      severity of DKA correlates well with the duration of inhospital stay, costs of
      care, requirement of ICU care, need for IV or non-IV, and mortality. This
      suggests that this classification system could be a valuable tool in predicting
      outcomes.

PMID- 30234056
TI  - Immunization uptake and its determinants among the internal migrant population
      living in nonnotified slums of Hyderabad city, India.
AB  - Background: The aim of this study is to assess the childhood immunization uptake
      and its determinants among the internal migrant population living in nonnotified
      slums of Hyderabad City, India. Methodology: This is a cross-sectional study of
      768 rural-urban migrant mothers with a child under 2 years of age residing for
      period minimum of 30 days, but not more than 10 years. Data were collected for
      sociodemographic details, health-seeking behavior, antenatal, postnatal services,
      and reception of vaccines appropriate for age. Results: Full immunization
      coverage among the children of migrants was same as the general population of the
      State of Telangana (66.7%). The likelihood of child's reception of full
      immunization decreases with age of the mother and rose with the attainment of
      higher education. The head of household of salaried class, expectant mothers
      utilizing antenatal services, and the visit of postnatal health worker for
      counseling of expectant mothers, were significantly associated with reception of
      full immunization. Immunization coverage rates of children of 12-23 months age is
      lower than the general population of Telangana. The frequency of visits by health
      worker is low. Conclusion: Immunization uptake among the migrants and vulnerable
      segments of the population can be increased by locating new settlements,
      improving utilization of services and capacity building of health staff.

PMID- 30234055
TI  - Integrated counseling and HIV testing centers of Delhi: An evaluation.
AB  - Background: HIV counseling and testing services are a key entry point in
      prevention of HIV infection, treatment, and care of people with HIV. Evaluation
      of counseling, testing, and referral services help to increase the effectiveness,
      efficiency, and quality of services delivered by providers by improving any
      deficiencies in availability, accessibility, and acceptability of testing and
      counseling services. The objective of this study was to evaluate the integrated
      counseling and testing centers (ICTC) in New Delhi. Materials and Methods: The
      evaluation study was conducted among ICTCs during 2014-2015. Twenty ICTCs of New
      Delhi were selected on the basis of population proportion to the size of clients
      catered. The study tool was pretested structured tool for evaluating HIV
      voluntary counseling and testing (VCT). The evaluation tool consists of an
      assessment of components including the availability of infrastructure, laboratory
      services, referral services, and staff availability. Counseling sessions were
      also observed for assessing content and quality. Means and proportions were
      calculated. Results: Twelve (60%) ICTCs had dedicated counseling rooms ensuring
      privacy for the clients. Waiting space was reported to be adequate in 16 (80%)
      ICTCs. Space within counseling room was observed to be adequate in 8 (40%) ICTCs.
      Counselors of both sexes were present in 12 (60%) ICTCs. Both external and
      internal quality assurance was observed in all ICTCs. Standard operating
      procedures were followed in 15 (75%) ICTCs. On observation of the counseling
      sessions, it was found that 67.4% of male counselors and 67.2% of female
      counselors addressed all the issues of content of counseling. Conclusion: ICTCs
      lack waiting area and adequate space in counseling room and required staff
      personnel. Records maintenance and laboratory quality control maintained by ICTCs
      were found to be adequate. The counseling rooms lack privacy that may compromise
      the confidentiality of clients. Few components of counseling need improvement.

PMID- 30234057
TI  - Menstrual abnormalities and their association with lifestyle pattern in
      adolescent girls of Garhwal, India.
AB  - Background: This study tried to find out the prevalence of menstrual
      abnormalities in adolescent girls and their association with dietary and exercise
      pattern in Garhwal region of India. Materials and Methods: In this study, cross
      sectional questionnaires survey was conducted in different schools of Garhwal.
      These questionnaires were based on socioeconomic data, dietary and physical
      activities, and menstrual abnormalities. Results: The age of menarche was 13.5 +/
      0.64 years. Dysmenorrhea (62.75%), premenstrual syndrome (PMS) (40.42%), and
      irregular cycle (28.72%) were observed common problems among adolescent girls.
      The result showed that dysmenorrhea, PMS, and menstrual irregularities were
      directly associated with dietary habits and physical activities. Dysmenorrhea was
      associated with eating junk food (66.10%), and PMS was associated with lacking of
      physical activities (78.94%). Conclusion: The result suggests that feeding habit
      and physical activities directly affecting the menstrual health of adolescent
      girls.

PMID- 30234058
TI  - The prevalence of obesity among adult population and its association with food
      outlet density in a hilly area of Uttarakhand.
AB  - Background: The rising burden of obesity is a threat to both developed and
      developing countries. Obesity is a killer lifestyle disease. Different aspects of
      the local environment play a key role in the occurrence of obesity. The present
      study was conducted to determine the prevalence of obesity among adult, its
      associated factors, and its relationship with retail food outlet density in
      Srikot, Uttarakhand. Materials and Methods: This study was a community-based
      cross-sectional study, carried out in Srikot, Uttarakhand, in 2016 among 155
      adults systematically sampled, aged above 20 years. A semi-structured pretested
      questionnaire was used to interview the participants, and anthropometry
      measurements were done. The details regarding the geographic location and count
      of outlets were carried out. Obesity was considered body mass index >=25 kg/m2.
      Results: In the present study, 61.3% were females. The mean age of the study
      participants was 38.3 (+/-13.6) years. The prevalence of overweight was 14.8% and
      obesity was 55.5%. A total of 92.9% of the study participants reported
      consumption of junk food. On mapping the study area, it was found that the total
      number of food outlets were 116. It was found that density of any food outlet per
      study participant was 0.7. Conclusion: The Srikot in Uttarakhand is in an early
      stage of urbanization as evident from the burden of obesity, and this might
      worsen by prevalent outlet density of food in the environment.

PMID- 30234059
TI  - Association of Vitamin D and secondary hyperparathyroidism with anemia in
      diabetic kidney disease.
AB  - Introduction: Anemia is common in Chronic Kidney Disease (CKD) and diabetes is a
      major leading risk factor for it. In Diabetic Kidney Disease (DKD), it worsens
      more, which further increases cardiovascular morbidity and mortality. Despite of
      adequate iron stores anemia persist, which may be due to impaired iron release
      from body stores that is unable to meet the demand for erythropoiesis (also
      called reticuloendothelial cell iron blockade). High parathyroid hormone (PTH)
      along with vitamin D, may be attributable for anemia. Methods: A cross-sectional
      study of 150 advanced (Stage 4 & 5) pre dialyzed DKD patients (GFR <30ml/min/1.73
      m2), aged 40-70 years were included over a period of 1 year. Any other
      concomitant illness/ drugs leading to anemia were excluded. Serum samples were
      collected and urea, creatinine, hemoglobin, iron profile, vitamin D, iPTH, uric
      acid, calcium, phosphorous and albumin levels were measured. A data base was
      constructed on Microsoft Excel 2007 and statistical analyses were performed using
      the SPSS software version 20.0 (IBM, NY, USA). Results: Stage 5 DKD had more
      pronounced anemia compared to stage 4 DKD (P < 0.001). Hemoglobin (Hb) was
      inversely correlated with iPTH (r = -0.74, P < 0.001) and was associated with
      vitamin D deficiency (r = 0.51, P < 0.001) but not with serum ferritin. DKD
      patients with low eGFR (r = -0.6, P < 0.001), vitamin D (r = -0.43, P < 0.001)
      and serum calcium (r = -0.37, P < 0.001) had higher iPTH. Secondary
      hyperparathyroidism (beta=-0.005; P < 0.001) and Vitamin D (beta=0.053; P < 0.01)
      were strong predictor for Hb while parameters of iron profile was not
      statistically significant. Conclusion: An efficient control of PTH hypersecretion
      is therefore required to achieve a better management of anemia as well as mineral
      metabolism in DKD patients.

PMID- 30234060
TI  - Household food security in an urban slum: Determinants and trends.
AB  - Introduction: As we are moving from millennium development goals to sustainable
      development goals, food insecurity is imposing a formidable challenge to the
      policymakers, especially in developing countries such as India. A survey
      conducted in the urban slum areas of Vellore district, 6 years back, had reported
      food insecurity as high as 75%. The current study was a resurvey to assess the
      food security status in the aforementioned area. Materials and Methods: A
      community-based survey was conducted in which data were collected using a self
      administered questionnaire from 150 households, selected through multistaged
      cluster sampling, who had given oral consent to be a part of the survey. The
      prevalence of food security calculated from this study was compared with the
      results from a previous survey to look for any significant improvement. Results:
      Nearly 42.7% of the households were food secure, while 26.7% were food insecure
      without hunger and 30.6% were food insecure with some degree of hunger. Low
      socioeconomic status (odds ratio [OR]: 3.25, 95% confidence interval [CI]: 1.29
      8.16; P < 0.012) and presence of debt (OR: 3.84, 95% CI: 1.90-7.73; P < 0.001)
      were the major risk factors for food insecurity. A comparison with the findings
      from the previous study has shown a statistically significant improvement in food
      security from 25.4% to 42.7% (Chi-square: 27.072, df: 2, P < 0.0001). Conclusion:
      Although food security levels have shown marked improvement over the years, much
      needs to be done for India to be free from the shackles of hunger.

PMID- 30234061
TI  - Family physicians health-related absenteeism at the Al-Wazarat Healthcare Center.
AB  - Background: In general, physicians and family physicians more specifically tend
      to treat themselves in an informal matter. The evidence suggests that family
      physicians have a tendency not to consult other physicians while they are sick
      and tend to self-treat. Health-related absenteeism among family physicians in
      primary care settings is an issue that needs to be addressed. Aim: The aim of
      this study is to identify the prevalence of health-related absenteeism among
      family physicians in Al-Wazarat Health Center and to investigate the medical
      causes associated with sickness absence. Methods: The study used cross-sectional
      design to investigate the prevalence of health-related absenteeism among family
      physicians in a primary care setting. Results: The study included 108 physicians
      from the Al-Wazarat Healthcare Center in Riyadh, KSA. On average, the physicians
      were absent for 2 days over the last year with 53.3% (64/108) have no health
      related absence days. The most common recorded reasons for work absence are the
      severity of illness 75.0% (81/108) and workload 63.0% (68/108). Influenza was the
      most common health condition that causes absenteeism 60.2% (65/108). The attitude
      toward working while ill scored 2.3 +/- 2.5, being responsible for affecting the
      patients if working while ill 8.0 +/- 2.8, physicians with chronic diseases
      should stay away from work 3.7 +/- 3.7, and the quality of healthcare service
      could be affected by the physician's illness 7.5 +/- 2.5. Conclusions: Further
      investigations are needed for more understanding of the physicians' tendencies
      and casual approach toward working with illness. Such understanding will help to
      formulate better guidelines for medical practices.

PMID- 30234062
TI  - Selfies: A boon or bane?
AB  - Background: Selfie deaths have become an emerging problem and we performed this
      study to assess the epidemiology of selfie-related deaths across the globe.
      Subject and Methods: We performed a comprehensive search for keywords such as
      "selfie deaths; selfie accidents; selfie mortality; self photography deaths;
      koolfie deaths; mobile death/accidents" from news reports to gather information
      regarding selfie deaths. Results: From October 2011 to November 2017, there have
      been 259 deaths while clicking selfies in 137 incidents. The mean age was 22.94
      years. About 72.5% of the total deaths occurred in males and 27.5% in females.
      The highest number of incidents and selfie-deaths has been reported in India
      followed by Russia, United States, and Pakistan. Drowning, transport, and fall
      form the topmost reasons for deaths caused by selfies. We also classified reasons
      for deaths due to selfie as risky behavior or non-risky behavior. Risky behavior
      caused more deaths and incidents due to selfies than non-risky behavior. The
      number of deaths in females is less due to risky behavior than non-risky behavior
      while it is approximately three times in males. Conclusion: "No selfie zones"
      areas should be declared across tourist areas especially places such as water
      bodies, mountain peaks, and over tall buildings to decrease the incidence of
      selfie-related deaths.

PMID- 30234063
TI  - Technical and Alarm signs for referral in adult patients with acute febrile
      illness: A study from a tertiary care hospital in North India.
AB  - Context: There is a huge burden of patients with acute febrile illness (AFI)
      during the post-monsoon season in India. It is very important to have a
      functioning triage system, whereby patients with high likelihood of developing a
      severe illness are referred to higher levels of care. Aim: The objective of this
      study was to identify the alarm signs which would help in triaging of those
      patients with AFI without any specific diagnosis. Methods: This was a
      retrospective review of records, whereby clinical and laboratory parameters of
      patients with AFI admitted in our tertiary care center between July 2016 and
      October 2016 were reviewed. Statistical Analysis Used: Appropriate tests of
      significance were applied using SPSS 21(Chicago, IL, USA) to find statistically
      significant differences between those who required mechanical ventilation,
      intensive care, ionotropic support, or higher intravenous antibiotics and those
      who recovered with minimal supportive care. Results: Presence of comorbidities,
      dyspnea, altered sensorium, features of myocarditis, hypotension, leukocytosis
      (>11,000/MUL), and acute kidney injury were significantly associated with
      requirement of higher levels of care, while presence of arthralgia, serositis,
      and leucopenia indicated a higher likelihood of recovery with minimal support.
      Conclusion: This article highlights the possibility of identification of simple
      alarm signs in patients with AFI which would indicate the need for higher levels
      of care.

PMID- 30234064
TI  - Effectiveness of iron-fortified infant cereals on prevalence of anemia among
      children.

PMID- 30234065
TI  - Target Hansen's disease.

PMID- 30234066
TI  - Erratum: Burnout and depression among medical residents in the United Arab
      Emirates: A multicenter study.
AB  - [This corrects the article on p. 435 in vol. 7, PMID: 30090790.].

PMID- 30234067
TI  - Association between Long Noncoding RNA ANRIL Expression Variants and
      Susceptibility to Coronary Artery Disease.
AB  - Animal cells possess thousands of long non-coding (lnc) RNAs, such as antisense
      noncoding RNA in the INK4 locus (ANRIL), which have regulatory roles in the
      cells' molecular mechanisms, including X-chromosome inactivation, and
      developmental processes. These lnc RNAs are known to influence the extensive
      spectrum of age-related disorders. Accordingly, there is evidence for the role of
      these lnc RNAs in cardiovascular diseases, particularly coronary artery diseases
      (CAD). The aim of this study was to assess whether the expression of the lnc RNA
      ANRIL was associated with a susceptibility to CAD by evaluating the expression
      level of the two transcripts of ANRIL. Peripheral blood was taken from fifty
      patients affected by CAD and relative expression of ANRIL was determined by Real
      Time PCR assay. The obtained data indicated that the EU741058 transcript
      expression level significantly decreased in CAD patients in comparison with the
      healthy individuals (P= 0.001). Furthermore, there was no significant association
      between the NR_003529 transcript expression, and CAD risk in Iranian patients
      (P=0.751). Our results suggest that the expression level of the EU741058
      transcript of ANRIL may be implicated in CAD development, creating a predictive
      biomarker for CAD patients in future.

PMID- 30234068
TI  - Downregulation of Matrix Metalloproteinases 2 and 9 is Involved in the Protective
      Effect of Trehalose on Spinal Cord Injury.
AB  - Upregulation of matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9
      contributes to secondary pathogenesis of spinal cord injury (SCI) via promoting
      inflammation. Recently, we have reported that trehalose suppresses inflammatory
      responses following SCI. Therefore, we investigated the effect of trehalose on
      MMP-2 and MMP-9 expression in SCI. A weight-drop contusion SCI was induced in
      male rats. Then, the animals received trehalose at three doses of 10 (T10), 100
      (T100) and 1000 (T1000) mM intrathecally. MMP-2 and MMP-9 transcripts were then
      measured in damaged spinal cord at 1, 3 and 7 days after trauma, and compared
      with vehicle and sham groups. Additionally, behavioral analysis was conducted for
      1 week using Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Our data
      showed an early upregulation of MMP-9 at 1 day post-SCI. However, MMP-2
      expression was increased at 3 days after trauma. Treatment with 10 mM trehalose
      significantly reduced MMP-2 expression in 3 and 7 days (P< 0.01) and MMP-9
      expression in 1, 3, and 7 days (P< 0.05) post-damage compared with vehicle.
      Nonetheless, downregulation of both MMPs was not observed in T100 and T1000
      groups. In addition, T10 group showed more rapid recovery of hind limb strength
      compared with T100 and T1000 groups. We propose that the neuroprotective effect
      of low dose trehalose is mediated by attenuation of MMP-2 and MMP-9 expression.

PMID- 30234069
TI  - A Comprehensive Genetic and Clinical Evaluation of Waardenburg Syndrome Type II
      in a Set of Iranian Patients.
AB  - Waardenburg syndrome (WS) is a neurocristopathy with an autosomal dominant mode
      of inheritance, and considerable clinical and genetic heterogeneity. WS type II
      is the most common type of WS in many populations presenting with sensorineural
      hearing impairment, heterochromia iridis, hypoplastic blue eye, and pigmentary
      abnormalities of the hair and skin. To date, mutations of MITF, SOX10, and SNAI2
      have been implicated in the pathogenesis of WS2. Although different pathogenic
      mutations have been reported in many ethnic groups, the data on Iranian WS2
      patients is insufficient. 31 WS2 patients, including 22 men and 9 women from 14
      families were included. Waardenburg consortium guidelines were employed for WS2
      diagnosis. WS2 patients underwent screening for MITF, SOX10, and SNAI2 mutations
      using direct sequencing and MLPA analysis. Clinical evaluation revealed prominent
      phenotypic variability in Iranian WS2 patients. Sensorineural hearing impairment
      and heterochromia iridis were the most common features (67% and 45%,
      respectively), whereas anosmia was the least frequent phenotype. Molecular
      analysis revealed a de novo heterozygous c.640C>T (p.R214X) in MITF and a de novo
      heterozygous SOX10 gross deletion in the study population. Our data help
      illuminate the phenotypic and genotypic spectrum of WS2 in an Iranian series of
      patients, and could have implications for the genetic counseling of WS in Iran.

PMID- 30234070
TI  - Overexpression of MiR-138 Inhibits Cell Growth and Induces Caspase-mediated
      Apoptosis in Acute Promyelocytic Leukemia Cell Line.
AB  - Dysregulated expression of miRNAs can play a vital role in pathogenesis of
      leukemia. The shortened telomere length, and elevated telomerase activity in
      acute promyelocytic leukemia cells are mainly indicative of extensive
      proliferative activity. This study aimed to investigate the effect of
      overexpression of miR-138 on telomerase activity, and cell proliferation of acute
      promyelocytic leukemia NB4 cells. MiR-138 was overexpressed in NB4 cells using
      GFP hsa-miR-138-expressing lentiviruses. hTERT mRNA and protein expression levels
      were assessed by qRT-PCR and western blot analysis. For evaluation of apoptosis,
      annexin-V staining and activation of caspases were assessed using flow cytometry
      and western blot analysis, respectively. Our data demonstrate that overexpression
      of miR-138 attenuated the hTERT mRNA and protein expression levels. In addition,
      cell growth was inhibited, and malignant cells underwent caspase mediated
      apoptosis in response to miR-138 overexpression. These findings suggest that loss
      of miR-138 expression may be associated with increased telomerase activity in NB4
      cells. Therefore, strategies for up-regulation of miR-138 may result in
      inhibition of malignant cell growth, and provide a promising therapeutic approach
      for acute promyelocytic leukemia.

PMID- 30234071
TI  - Epidemiology of Infantile Visceral Leishmaniasis in Western Algerian And The
      Convenience of Serum For The Disease Diagnosis by PCR and Immunochromatography.
AB  - Epidemiological situation of infantile visceral leishmaniasis (IVL), which is a
      public health problem in Algeria, is almost unknown in the cities of Western part
      of the country. The aim of this study was to analyze the epidemiological,
      clinical, biological, therapeutic, and evolutionary aspects of IVL in Western
      Algeria, to evaluate the performance of the immunochromatography as a rapid
      diagnostic test of the disease, and to propose a diagnosis approach by real-time
      polymerase chain reaction (RT-PCR) assay from the serum. This prospective study
      was performed on 63 suspicious cases of visceral leishmaniasis collected from the
      infectious diseases department at the Pediatric Hospital of Oran from January
      2012 to July 2017. For each patient, the epidemiological parameters, and the
      clinical and biological data were collected. Bone marrow and blood samples were
      drawn from all cases. Bone marrow was performed to research amastigote forms of
      Leishmania and to identify the species by PCR-sequencing. Blood samples were used
      to detect anti-Leishmania antibodies as well as parasite DNA. Patients from the
      Western regions were mostly from rural areas. Sensitivity of RT-PCR from the bone
      marrow and from serum was 95.45% and 94.44%, respectively. The
      immunochromatography allowed the disease's diagnosis for 11 cases whose myelogram
      did not confirm the presence of the amastigote forms of Leishmania.
      Immunochromatography was revealed to be a good technique for disease diagnosis
      regarding the strongly evocative clinical signs. The results also suggest the
      interest of the RT-PCR assay from patient serum as a non-invasive sample, in the
      detection of parasite DNA.

PMID- 30234072
TI  - Marine Actinomycetes with Probiotic Potential and Bioactivity against Multidrug
      resistant Bacteria.
AB  - Considering antimicrobial resistance problem, marine microorganisms with the
      bioactivity against multi-drug resistant (MDR) pathogens have attracted many
      scientific interests. To address this issue, a total of 21 marine actinomycetes
      isolated from the Caspian Sea have been screened out. Primary screening via cross
      streak method revealed that 3 strains: MN2, MN39, and MN40 produce antimicrobial
      agents with wide spectrum activity. In the second step, the potent strains were
      characterized morphologically, and then identified genetically using 16S rRNA
      analysis. After that, the bioactivity of the ethyl acetate extracts of liquid
      culture against some MDR bacteria has been studied using disc diffusion method.
      Finally, the exoenzymatic activity of the strains, and the anti-vibrio activity
      of the extracts have been evaluated. The nucleotide sequence of the 16S rRNA gene
      (1.5 kb) showed that the potent strains belong to the genus Streptomyces. The
      results of disk diffusion method indicated that among the 3 potent isolates, MN39
      and MN2 produce biomolecules with antibacterial activity against MDR bacteria
      specially methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin
      resistant Enterococcus (VRE). In addition, potent strains showed remarkable anti
      vibrio activity as well as extracellular enzyme production including amylase and
      protease. The results of this study revealed that the marine actinomycetes
      isolated from the sediments of Caspian Sea produce biomolecules effective against
      MDR bacteria, and suggested that these strains deserve to be studied as potential
      probiotics due to their anti-vibrio activity besides exoenzyme production.

PMID- 30234073
TI  - In silico Homology Modeling and Epitope Prediction of NadA as a Potential Vaccine
      Candidate in Neisseria meningitidis.
AB  - Neisseria meningitidis is a facultative pathogen bacterium which is well founded
      with a number of adhesion molecules to facilitate its colonization in human
      nasopharynx track. Neisseria meningitidis is a major cause of mortality from
      severe meningococcal disease and septicemia. Neisseria meningitidis adhesion,
      NadA, is a trimeric autotransporter adhesion molecule which is involved in cell
      adhesion, invasion, and antibody induction. It is identified in approximately 50%
      of N. meningitidis isolates, and is established as a vaccine candidate due to its
      antigenic effects. In the present study, we exploited bioinformatics tools to
      better understand and determine the 3D structure of NadA and its functional
      residues to select B cell epitopes, and provide information for elucidating the
      biological function and vaccine efficacy of NadA. Therefore, this study provided
      essential data to close gaps existing in biological areas. The most appropriate
      model of NadA was designed by SWISS MODEL software and important residues were
      determined using the subsequent epitope mapping procedures. Locations of
      important linear and conformational epitopes were determined and conserved
      residues were identified to broaden our knowledge of efficient vaccine design to
      reduce meningococcal infectioun in population. These data now provide a theme to
      design more broadly cross-protective antigens.

PMID- 30234075
TI  - Artificial urinary sphincters for treating postprostatectomy incontinence: A
      contemporary experience from the UK.
AB  - Objectives: To report a real-time contemporary practice and outcome of artificial
      urinary sphincter (AUS) in patients with postradical prostatectomy urinary
      incontinence (PPI) in the UK. Methods: A retrospective observational study of
      patients who underwent AUS implantation (AMS 800) from 2007 to 2013. Data were
      collected on patients' demographics, infection and erosion rate, mechanical
      failure, reoperation, and continence rates. The study strictly included patients
      with postradical PPI only. Minimum follow-up was 15 months. Results: Eighty-four
      AUSs were implanted over a period of 6 years. Patients' age ranged between 51 and
      78 (median 69, mean 69.25) years. Median follow-up was 37 months, mean 39 months,
      and range 15-92 months. Among the 83 follow-up patients, 38.5% (32/83) reported
      that they were completely dry with no pads; 42.2% (35/83) of patients were
      socially continent (using 1 pad/day) and 19.3% (16/83) using >=2 pads/day. One
      patient was lost to follow-up. Reoperation rate was 13.25% (11/83), including
      nine mechanical failures (10.8%). Two implant infections (2.4%) required
      explantation, out of which one had erosion (1.2%). Bladder overactivity developed
      in 6% of patients. Of the 83, 15 (18%) had pelvic radiotherapy. Conclusion: The
      implantation of AUS in patients with post-PPI has lower complications and
      reoperation rates than historical impression painted in the literature. This can
      be beneficial in counseling as well as during the education process of patients
      going through the decision process for prostate cancer treatment. Furthermore,
      these figures can add to our quest to increase the awareness of the success of
      anti-incontinence surgery among patients.

PMID- 30234076
TI  - Handling of Breast Milk by Neonatal Units: Large Differences in Current Practices
      and Beliefs.
AB  - Background: Breast milk (BM) for premature infants is subjected to multiple steps
      of processing, storage and distribution. These steps may influence the quality
      and safety of BM. Guidelines concerning the use of mother's own milk are either
      not available or limited to specific aspects of BM handling and are based on
      evidence of variable strength. This may result in diverse BM handling routines by
      health care professionals. Objective: We surveyed neonatal units to increase the
      knowledge about the current practice of BM handling routines of mother's own milk
      and to identify controversial aspects that could give directions for future
      research. Methods: An online-based questionnaire was sent to 307 different
      neonatal departments providing level III to level I neonatal care within Germany,
      Austria and Switzerland. Practices concerning screening for cytomegalovirus and
      BM bacteria, pasteurization, fortification, storage, workforce and the incidence
      of BM administration errors were surveyed. Results: A total of 152 units, 56% of
      contacted level III units and 51% of level II units, participated in the survey
      (Germany 53%, Switzerland 71%, and Austria 56%). We found differences concerning
      indication and method of CMV inactivation (performed by 58%), bacterial count
      screening (48%) and bacterial count reduction (17%) within participating units.
      Thirty different thresholds for bacterial BM counts were reported by 65 units,
      resulting in pasteurization or discarding of BM. The use of nutrient analysis
      (12%) and fortification regimens in addition to standard multicomponent
      fortifiers (58%) using either individual (93%), targeted (3%), or adjusted (4%)
      fortification protocols varied profoundly. There is a high variability in staff
      and available facilities for BM handling. 73% of units report about BM
      administration errors. Conclusion: There is a wide variability in most aspects of
      BM handling in the participating units. Despite limited evidence labor and cost
      intensive procedures are applied which may have an impact on BM quality.

PMID- 30234077
TI  - Prospective Cohort Study Investigating the Safety and Efficacy of Ambulatory
      Treatment With Oral Cefuroxime-Axetil in Febrile Children With Urinary Tract
      Infection.
AB  - Aims: To assess the safety and efficacy of ambulatory oral cefuroxime-axetil
      treatment in children presenting with first febrile urinary tract infection (UTI)
      in terms of resolution of fever, antibiotics tolerance, bacterial resistance, and
      loss to ambulatory follow-up. Methods: Two-year prospective single-center
      evaluation of the local protocol of oral ambulatory treatment of children
      presenting first febrile urinary tract infection (UTI). Results: From October
      2013 to October 2015, 82 children were treated ambulatory with oral cefuroxime
      axetil. The median age was 8 months. When analyzing those 82 children treated
      orally, 51 (62%) completed oral treatment, 14 (17%) missed their scheduled follow
      up visits (3 patients at day 2 and 11 patients at week 2), and 17 (21%) were
      switched to IV therapy for the following reasons: vomiting in 9, persistent fever
      in 5, antibiotic resistance in 2 and bacteremia in 1. Six children (8%) presented
      recurrent UTI after a median of 5 months of follow-up. Conclusions: This 2-year
      evaluation suggests that oral treatment with cefuroxime-axetil in febrile UTI is
      feasible but should be implemented with caution. Home-treated children require
      reevaluation during treatment since 21% of our cohort had to be temporarily
      switched to parenteral therapy and 17% did not attend scheduled follow-up visits
      during oral treatment.

PMID- 30234074
TI  - Three-dimensional tumor cell cultures employed in virotherapy research.
AB  - Oncolytic virotherapy constitutes an upcoming alternative treatment option for a
      broad spectrum of cancer entities. However, despite great research efforts, there
      is still only a single US Food and Drug Administration/European Medicines Agency
      approved oncolytic virus available for clinical use. One reason for that is the
      gap between promising preclinical data and limited clinical success. Since
      oncolytic viruses are biological agents, they might require more realistic in
      vitro tumor models than common monolayer tumor cell cultures to provide
      meaningful predictive preclinical evaluation results. For more realistic invitro
      tumor models, three-dimensional tumor cell-culture systems can be employed in
      preclinical virotherapy research. This review provides an overview of spheroid
      and hydrogel tumor cell cultures, organotypic tumor-tissue slices, organotypic
      raft cultures, and tumor organoids utilized in the context of oncolytic
      virotherapy. Furthermore, we also discuss advantages, disadvantages, techniques,
      and difficulties of these three-dimensional tumor cell-culture systems when
      applied specifically in virotherapy research.

PMID- 30234078
TI  - Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in
      Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
AB  - Background: Concise methodological directions for administration of serial
      cardiopulmonary exercise testing (CPET) are needed for testing of patients with
      Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Maximal CPET is used
      to evaluate the coordinated metabolic, muscular, respiratory and cardiac
      contributions to energy production in patients with ME/CFS. In this patient
      population, CPET also elicits a robust post-exertional symptom flare (termed,
      post-exertional malaise); a cardinal symptom of the disease. CPET measures are
      highly reliable and reproducible in both healthy and diseased populations.
      However, evidence to date indicates that ME/CFS patients are uniquely unable to
      reproduce CPET measures during a second test, despite giving maximal effort
      during both tests, due to the effects of PEM on energy production. Methodology:
      To document and assess functional impairment due to the effects of post
      exertional malaise in ME/CFS, a 2-day CPET procedure (2-day CPET) has been used
      to first measure baseline functional capacity (CPET1) and provoke post-exertional
      malaise, then assess changes in CPET variables 24 h later with a second CPET to
      assess the effects of post-exertional malaise on functional capacity. The second
      CPET measures changes in energy production and physiological function,
      objectively documenting the effects of post-exertional malaise. Use of CPET as a
      standardized stressor to induce post-exertional malaise and quantify impairment
      associated with post-exertional malaise has been employed to examine ME/CFS
      pathology in several studies. This article discusses the results of those
      studies, as well as the standardized techniques and procedures for use of the 2
      day CPET in ME/CFS patients, and potentially other fatiguing illnesses.
      Conclusions: Basic concepts of CPET are summarized, and special considerations
      for performing CPET on ME/CFS patients are detailed to ensure a valid outcome.
      The 2-day CPET methodology is outlined, and the utility of the procedure is
      discussed for assessment of functional capacity and exertion intolerance in
      ME/CFS.

PMID- 30234079
TI  - Paracorporeal Lung Devices: Thinking Outside the Box.
AB  - Extracorporeal Membrane Oxygenation (ECMO) is a resource intensive, life
      preserving support system that has seen ever-expanding clinical indications as
      technology and collective experience has matured. Clinicians caring for patients
      who develop pulmonary failure secondary to cardiac failure can find themselves in
      unique situations where traditional ECMO may not be the ideal clinical solution.
      Existing paracorporeal ventricular assist device (VAD) technology or unique
      patient physiologies offer the opportunity for thinking "outside the box." Hybrid
      ECMO approaches include splicing oxygenators into paracorporeal VAD systems and
      alternative cannulation strategies to provide a staged approach to transition a
      patient from ECMO to a VAD. Alternative technologies include the adaptation of
      ECMO and extracorporeal CO2 removal systems for specific physiologies and
      pediatric aged patients. This chapter will focus on: (1) hybrid and alternative
      approaches to extracorporeal support for pulmonary failure, (2) patient selection
      and, (3) technical considerations of these therapies. By examining the successes
      and challenges of the relatively select patients treated with these approaches,
      we hope to spur appropriate research and development to expand the clinical
      armamentarium of extracorporeal technology.

PMID- 30234080
TI  - Respiratory Muscle Strength and Exercise Performance in Cystic Fibrosis-A Cross
      Sectional Study.
AB  - Introduction: Decreased respiratory muscle strength in patients with cystic
      fibrosis (CF) may cause progressive exercise intolerance during cardiopulmonary
      exercise testing (CPET), and may contribute to the development of chronic
      respiratory insufficiency. The aim of this study is to evaluate exercise
      tolerance during CPET of children and adults with clinically stable CF who
      exhibit different respiratory muscle strength. Methods: Sixty-nine clinically
      stable CF subjects aged 8-33 years underwent spirometry, body plethysmography,
      CPET, and respiratory muscle strength measurement. Respiratory muscle strength
      was measured using maximal inspiratory pressures (Pimax) and maximal expiratory
      pressures (Pemax). Participants were stratified into three groups according to
      Pimax values:below normal (<=80% predicted), normal (81-100% predicted), and
      above normal (>100% predicted). A similar stratification of participants was made
      according to Pemax values. The oxygen consumption on peak load (VO2peak) was
      expressed relative to BM (VO2peak/kg), relative to BM raised by the exponent of
      0.67 (VO2peak/kg0.67) and as log-linear adjustment of VO2peak (VO2peak/kg-alo).
      Results: Participants with low Pemax values had a lower mean maximum load per
      kilogram/predicted (Wmax; p = 0.001) VO2peak/kg (p = 0.006), VO2peak/kg0.67 (p =
      0.038) and VO2peak/kg-alo (p = 0.001). There were no significant differences in
      exercise tolerance parameters with regard to Pimax values. Stepwise multiple
      linear regressions confirmed that Pemax (B = 24.88, beta = 0.48, p < 0.001) was
      the most powerful predictor of Wmax. There were no statistically significant
      differences in age, lung function parameters, exacerbation score, or respiratory
      muscle strength according to gender. Conclusions: In subjects with clinically
      stable CF, expiratory muscle strength is associated with a decrease in exercise
      performance during CPET and can predict exercise intolerance. Increase in
      expiratory muscle strength by patient specific rehabilitation protocols would
      result in improvement of exercise tolerance.

PMID- 30234081
TI  - The Impact of Typhoon Haiyan on Health Staff: A Qualitative Study in Two
      Hospitals in Eastern Visayas, The Philippines.
AB  - Background and objective: Understanding how natural disasters affect their
      victims is key to improve prevention and mitigation. Typhoon Haiyan strongly hit
      the Philippines in 2013. In Leyte, health staff of two hospitals had a key role
      as responders, but also as victims. Scarce literature is available on how health
      staff may be affected when being disasters' victims. We therefore aimed to
      understand Haiyan's impact for health staff at personal and work level. Methods:
      We conducted semi-structured interviews in the two hospitals with doctors,
      nurses, midwives, watchmen and administrative staff in September 2016. We used a
      thematic analysis. Results: The three main aspects reported as influencing staff
      were accessibility, safety and emotional aspects. Accessibility was a main
      difficulty, which prevented some staff from reaching the hospital, causing other
      staff staying longer on-call. Personal and family safety were affected, and due
      to remaining on-call immediately after Haiyan, staff members reported lack of
      information about their family situation. Faith was an emotional aspect
      repeatedly mentioned as a coping mechanism, and commitment to serve patients was
      for some respondents an essential argument to stay on duty. Conclusions: Conflict
      between personal and professional concerns was present in health staff, making it
      difficult for them to prioritize work. Feeling unsafe was a common experience
      among health staff which influenced attendance to the hospital. Including
      temporary housing for staff and relatives close by the hospital can improve the
      extensive disaster risk during the typhoon season. In addition, established
      communication channels should be prioritized for staff on duty to find out about
      family members' wellbeing. We recommend faith and commitment to serve patients to
      be included in the preparedness programs in this setting.

PMID- 30234082
TI  - Unpacking Hispanic Ethnicity-Cancer Mortality Differentials Among Hispanic
      Subgroups in the United States, 2004-2014.
AB  - Introduction: National data on the epidemiology of cancer are commonly reported
      by broad racial/ethnic categories, such as "Hispanic." However, few studies have
      disaggregated Hispanic groups and explored mortality differentials in this
      heterogeneous population. This paper aims to further examine cancer mortality
      differentials among Hispanic subgroups in the U.S. Materials and Methods: The
      study examined cancer deaths in the United States from 2004 to 2014 among
      decedents classified as Mexican, Puerto Rican, Cuban, Dominican, Central/South
      American and non-Hispanic white on the death certificate among those who were 20
      years or older at the time of death. Data were obtained from the National Vital
      Statistics System. Sex-specific age-adjusted mortality rates were computed for a
      10-year period and each individual year, for all cancers combined. Differences by
      age group, cancer sites, and age distribution were also assessed. Results: A
      total of 296,486 Hispanic cancer deaths were identified. Mortality rates of the
      Hispanic subgroups compare favorably with those of non-Hispanic whites. The
      mortality rates for Mexicans are very similar to those of all Hispanics combined,
      whereas the rates for Cuban and Puerto Ricans are higher. Dominicans and
      Central/South Americans had the overall lowest mortality rates. Statistically
      significant decreases in cancer mortality rates were noted in some sub-groups,
      but rates increased among Dominican women. Age-adjusted mortality rates by cancer
      site varied among Hispanics subgroups and gender. Among Cubans, only 5% of cancer
      deaths occurred before the age of 50 compared to 16% of cancer deaths among
      Central/South American. Conclusion: While it is common to present data on the
      burden of cancer among Hispanics as an aggregate group, this study illustrates
      that the burden of cancer varies by Hispanic subgroups. The disaggregation of
      Hispanics by ancestry/country of origin allows for a clearer understanding of the
      health status of this growing population and is needed if health disparities are
      to be adequately identified, understood and addressed.

PMID- 30234083
TI  - A Systems Thinking Approach to Understanding and Demonstrating the Role of Peer
      Led Programs and Leadership in the Response to HIV and Hepatitis C: Findings From
      the W3 Project.
AB  - The central role of community and peer-led programs has been a key characteristic
      of the Australian partnership response to HIV and hepatitis C since the beginning
      of the epidemics. Despite this, peer-led programs continue to have limited
      capacity to demonstrate their role and value as part of a multi-sectoral
      response. What makes one peer-led program a better investment than another? What
      role does the rest of the sector have in ensuring we gain the most value from
      these investments? To investigate this, we facilitated interactive systems
      thinking methods with 10 programs working within communities of people who inject
      drugs, gay men, sex workers and people living with HIV across Australia. This
      included articulating program theories in diagram and textual form to help us
      understand the role of peer-based programs promoting peer leadership within the
      Australian HIV and hepatitis C responses. Our aim was to develop a framework for
      monitoring and evaluation that could be applied to peer led programs at different
      levels and in different contexts. We found that for peer-led programs to fulfill
      their role, and to navigate the rapid changes occurring in the both epidemics,
      they need to: demonstrate the credibility of their peer and community insights;
      continually adapt to changing contexts and policy priorities in tandem with their
      communities; and maintain influence in both community and policy systems. We
      developed a framework of four key functions (Engagement, Alignment, Adaptation,
      and Influence) which peer-based programs need to demonstrate, which form the
      basis for identifying quality indicators. This article presents a new way of
      framing and monitoring investments in peer-led programs and peer eadership
      actions by these programs. If health policy is committed to strengthening the
      leadership shown by affected communities, then we need to understand, enhance,
      monitor and value the role of peer-led programs and peer leadership within the
      overall prevention system. We believe the W3 framework, drawing on systems
      thinking and modeling, can support funders, policy-makers and programs to achieve
      this.

PMID- 30234084
TI  - Limpet (Scutellastra cochlear) Recovered From Some Estuaries in the Eastern Cape
      Province, South Africa Act as Reservoirs of Pathogenic Vibrio Species.
AB  - Limpet (Scutellastra cochlear) serves as seafood recipe and an important member
      of the aquatic food chain. It is an abundant mollusc in some aquatic environment
      in South Africa. In this study, we investigated the potential of the molluscs
      harvested from the Buffalo, Swartkops, and Kowie estuaries in the Eastern Cape
      Province, South Africa to serve as transient or maintenance reservoir of Vibrio
      species. The mollusc and source water samples were collected monthly from the
      rivers between December 2016 and November 2017. The reservoir category of the
      limpet samples recovered was determined by employing the combination of MPN-PCR
      method and statistical analysis (comparison of mean and proportion tests). The
      densities of Vibrio spp. in limpet and their source water samples were determined
      using MPN-PCR methods. Presumptive isolates were recovered by processing the
      samples with thiosulfate-citrate-bile salts-sucrose agar and where necessary,
      samples were enriched with alkaline peptone water. The presumptive isolates were
      identified using PCR methods with emphasis on six Vibrio species of public health
      importance. Vibrio spp. were detected in all the limpet samples but not in all
      the water samples. The densities of Vibrio spp. in the limpet samples were more
      than the densities of Vibrio species in their source water and these were
      significant at P < 0.05. In like manner, five out of the six key Vibrio pathogens
      targeted in this study were more prevalent in limpet samples than in source water
      samples. Based on our findings, we concluded that our method though could be
      improved on, is efficient for the determination of reservoir types of bacterial
      carrying organisms. We also concluded that the limpet found in the estuaries are
      not just a transient but a maintenance reservoir of Vibrio spp. which could cause
      vibrio-related infections.

PMID- 30234086
TI  - How Social Networks May Influence Cancer Patients' Situated Identity and Illness
      Related Behaviors.
AB  - Little research is currently available that captures variation in the degree to
      which individuals who have, or had cancer in the past (but are in remission)
      integrate their cancer experience into their sense of self or their cancer
      associated identity. Such research should cover how those identities shape
      personal narratives within existing or new social networks so that, ultimately,
      we understand the implications for treatment choices and health outcomes.
      Particularly understudied are the social factors influencing the incorporation of
      cancer into identity, learning, and behavior. Social network analysis captures
      specific relationships, what they offer, and the structure or constellation of
      these relationships around someone who has cancer or has had cancer. Some studies
      point to potential cultural differences in ethnic or social groups in how social
      influences on the cancer experience play out in terms of individual coping
      strategies. In some populations, social cohesion or tight networks are common and
      of particular importance to individuals and include social institutions like
      church communities. Social status might also generate social pressures not
      typically noticed or experienced by other groups. We will discuss how social
      network analysis can be used to elucidate these factors and, conversely, how the
      specific context of cancer diagnosis can be used through social network analysis
      to better understand the role of community in helping individuals address
      situations of severe adversity.

PMID- 30234085
TI  - Sedentary Behavior at Work and Cognitive Functioning: A Systematic Review.
AB  - Background: It is now well-established that sedentarity has a negative impact on
      the physiological functioning and health of humans, whereas very little is known
      about the psychological repercussions, especially in cognitive functioning. Yet,
      studying the cognitive effects of the sedentary lifestyle is particularly
      relevant in the short term for productivity and in the long term for cognitive
      health (accelerated aging). This systematic review therefore aims to make an
      inventory of the potential cognitive effects of sedentarity at the workplace.
      Methods: Pubmed, PsycINFO, Cochrane, Web of Science, and Scopus were searched for
      English-language peer-reviewed articles published between January 1, 2000 and
      December 31, 2017 to identify studies including sedentary behavior and objective
      measures from cognitive domains (cognitive inhibition, cognitive flexibility,
      working memory, etc.). To carry out this systematic review, the 3 keywords
      "Sedentary" and "Cognition" and "Work" (and their derivatives) had to appear in
      the title or in the summary of the paper. Results: Of the 13 papers that met the
      inclusion criteria, 9 were short-term interventions, 3 medium-term interventions,
      and 1 long-term intervention. Nine of them reported non-significant results. Two
      studies study reported deterioration in cognitive performance. Two reported an
      improvement in performance in cognitive tasks with one study with overweight
      adults and the only one study with a long-term intervention. However, these
      studies intend to reduce sedentary behavior, but do not allow answering the
      question of the potential cognitive effects of the sedentary lifestyle.
      Conclusion: These data suggest that sedentary behavior is not associated with
      changes in cognitive performance in interventions that intend to reduce sedentary
      behavior. Then, and given the trend toward increased time in sedentary behavior,
      long-term prospective studies of high methodological quality are recommended to
      clarify the relationships between sedentary behavior and the cognitive
      functioning. Our systematic review identifies also the need for retrospective,
      longitudinal, or epidemiologic studies. It also recognizes the need to
      standardize methodology for collecting, defining, and reporting sedentary
      behavior and the need to standardize the cognitive tests used. The relationship
      between sedentary behavior and cognitive functioning remaining uncertain, further
      studies are warranted for which 8 recommendations are proposed.

PMID- 30234088
TI  - Evaluation of the Involvement of Pharmacists in Diabetes Self-Care: A Review From
      the Economic Perspective.
AB  - Objectives: To analyze the studies encompassing the involvement of pharmacists in
      diabetes self-care. Method: We reviewed studies conducted from 2005 to 2017 on
      the involvement of pharmacists in diabetes self-care. The keywords mainly used in
      this search are pharmacoeconomic analysis, diabetes self-care, pharmacist
      involvement,cost-effectiveness analysis, cost of utilization, cost of illness,
      cost of minimization and cost-benefit analysis. PubMed, Science Direct, Springer
      Link and Medline searched for the relevant studies. These databases searched for
      full text articles ranging from 2007 to 2017. We tried to limit the search with
      the inclusion of studies having any sort of pharmacoeconomically relevant
      component. Key Findings: Cost of illness varied among the countries in managing
      diabetes mellitus, and the cost of managing diabetes complications were twice the
      cost of management of diabetes. Continuous involvement of the pharmacist in
      primary health care is a cost-effective strategy and pronounced to be essential
      for helping diabetes patient in controlling and managing their disease.
      Implementation of diabetes self-care by pharmacists such as lifestyle
      intervention rendered improved quality of life of patient without any increase in
      health care cost. Self-care management generates intensive blood glucose control
      and improved quality of life. Conclusions: Implementation of diabetic self-care
      intervention including intensive lifestyle intervention, education, self
      monitoring of blood glucose and adherence toward medication-initiated reduction
      in the overall healthcare cost of diabetic patients compared to patients relying
      on only any one of the interventions. Impact of diabetes self-care intervention
      by pharmacist reported to significantly reduce the HbA1C levels of diabetic
      patients along with the reduction of yearly healthcare cost. This review showed
      that pharmacist involvement in diabetes self-care interventions prove to be cost
      effective and can significantly affect the condition of the diabetic patients and
      reduces the risk of complications.

PMID- 30234087
TI  - Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans.
AB  - Monkeypox is an emerging zoonotic disease recognized as the most important
      orthopoxvirus infection in humans in the smallpox post-eradication era. The
      clinical presentation of monkeypox is similar to the one of smallpox. The case
      fatality rate of monkeypox (10%) lies between the case fatality rate of variola
      major (30%) and variola minor (1%). The disease is endemic in the Democratic
      Republic of the Congo, but other countries of Central and West Africa either
      reported cases of monkeypox in humans or circulation in wildlife. The disease was
      also imported once into the USA. The disease has always been considered rare and
      self-limiting, however recent sporadic reports suggest otherwise. Unfortunately,
      the collected data is limited, dispersed and often incomplete. Therefore, the
      objective of this review is to trace all reported human monkeypox outbreaks and
      relevant epidemiological information. The frequency and geographical spread of
      human monkeypox cases have increased in recent years, and there are huge gaps in
      our understanding of the disease's emergence, epidemiology, and ecology. The
      monkeypox virus is considered a high threat pathogen causing a disease of public
      health importance. Therefore, there is an urgent need to focus on building
      surveillance capacities which will provide valuable information for designing
      appropriate prevention, preparedness and response activities.

PMID- 30234089
TI  - Inflammatory Markers in Patients Using Domiciliary Non-invasive Mechanical
      Ventilation: C Reactive Protein, Procalcitonin, Neutrophil Lymphocyte Ratio.
AB  - Aim: Early identification and treatment of infections in patients using
      domiciliary non-invasive mechanical ventilation (NIMV) due to chronic respiratory
      failure (CRF) can reduce hospital admissions. We assessed C-reactive protein
      (CRP), procalcitonin, and neutrophil lymphocyte ratio (NLR) as indicators of
      infection/inflammation. Methods: The study was designed as a retrospective,
      observational, cross-sectional study, and was performed in 2016 in an intensive
      care unit outpatient clinic in patients using NIMV. Patients who came to the
      outpatient clinic with dyspnea, increased sputum, increased prothrombin, and who
      had hemogram, procalcitonin, and serum CRP, NLR, and PLT/MPV levels assessed,
      were enrolled into the study. Demographic characteristics, co-morbid diseases,
      respiratory symptoms, hemogram, biochemistry, CRP, and procalcitonin values in
      stable and acute attack patients were recorded from patient files. The
      descriptive statistics and CRP, NLR, and procalcitonin values were assessed.
      Results: During the study period, 49 patients (24 female) with chronic
      obstructive pulmonary disease (COPD, n = 24), obesity hypoventilation syndrome
      (OHS, n = 15), or interstitial lung disease, n = 10), and having had three
      inflammatory markers assessed, were included in the study. Their mean age was 67
      (SD +/- 12). Stable patients vs. those who had an acute attack was 41 vs. eight,
      and within 7 days of outpatient admission four patients were hospitalized. CRP,
      NLR, and PLT/MPV values were similar in patients' who had sputum purulence, and
      an increase in dyspnea and sputum, but procalcitonin was significantly higher in
      patients who had an acute attack. Procalcitonin was not correlated with CRP, NLR,
      and PLT/MPV. Conclusions: Patients with CRF had similar levels of CRP and NLR
      during a stable and acute attack state. Procalcitonin may be a better marker for
      therapeutic decisions in advanced chronic inflammatory diseases.

PMID- 30234092
TI  - A Next Generation Assets-Based Public Health Intervention Development Model: The
      Public as Innovators.
AB  - In the public health field, the design of interventions has long been considered
      to be the province of public health experts. In this paper, I explore an
      important complement to the traditional model: the design, prototyping, and
      implementation of innovative public health interventions by the public (users)
      themselves. These user interventions can then be incorporated by public health
      experts, who in turn design, support, and implement improvements and diffusion
      strategies as appropriate for the broader community. The context and support for
      this proposed new public health intervention development model builds upon user
      innovation theory, which has only recently begun to be applied to research and
      practice in medicine and provides a completely novel approach in the field of
      public health. User innovation is an assets-based model in which end users of a
      product, process, or service are the locus of innovation and often more likely
      than producers to develop the first prototypes of new approaches to problems
      facing them. This occurs because users often possess essential context-specific
      information about their needs paired with the motivation that comes from directly
      benefiting from any solutions they create. Product producers in a wide range of
      fields have, in turn, learned to profit from the strengths of these user
      innovators by supporting their grass-roots, leading-edge designs and field
      experiments in various ways. I explore the promise of integrating user-designed
      and prototyped health interventions into a new assets-based public health
      intervention development model. In this exploration, a wide range of lead user
      methods and positive deviance studies provide examples for identification of user
      innovation in populations, community platforms, and healthcare programs. I also
      propose action-oriented and assets-based next steps for user-centered public
      health research and practice to implement this new model. This approach will
      enable us to call upon the strengths of the communities we serve as we develop
      new methods and approaches to more efficiently and effectively intervene on the
      varied complex health problems they face.

PMID- 30234090
TI  - Can a Village Headman Use an Electronic Village Register and a Simplified
      Community-Based Verbal Autopsy Tool to Record Numbers and Causes of Death in
      Rural Malawi?
AB  - Introduction: Most people in Africa die without appearing in official vital
      statistics records. To improve this situation, Malawi has introduced solar
      powered electronic village registers (EVR), managed by village headmen, to record
      birth and death information for production of vital statistics. The EVR is
      deployed in 83 villages in Traditional Authority Mtema, Lilongwe, which is an
      area without electricity. In 17 villages, village headmen were also trained to
      use a simple verbal autopsy (VA) tool adapted from one developed by the World
      Health Organization (WHO). Study objectives were to (i) document numbers and
      causes of death occurring in 17 villages between April 2016 and September 2017,
      and (ii) assess percentage measures of agreement on causes of death as recorded
      by village headmen using a simple VA tool and by a team of health surveillance
      assistant (HSA)/medical doctor using the WHO VA tool. Methods: The study was in
      two-parts: (i) a cross-sectional study using secondary data from the EVR; (ii)
      primary data collection study comparing causes of death obtained by village
      headmen using a simple VA tool and by HSA/medical doctor using the WHO VA tool.
      Results: Over 18 months, 120 deaths were recorded by EVR in 14,264 residents -
      crude annual death rate 5.6/1,000 population. Median age at death was 43 years
      with 69 (58%) deaths being in males. Death occurred at home (75%) and at health
      facility (25%). Malaria, diarrhoeal disease, pulmonary tuberculosis, acute
      respiratory infection, and stroke accounted for 56% of deaths recorded by village
      headmen using the simple VA tool. Causes of death between village headmen and the
      HSA/medical doctor team were compared for 107 deaths. There was full agreement in
      causes of death in 33 (31%) deaths, mostly for malaria, severe anemia,
      intentional self-harm, cancer, and epilepsy. Unknown-sudden death and sepsis
      recorded by the HSA/medical doctor team were responsible for most disagreements.
      Conclusion: It is feasible for village headmen in rural Malawi to use an EVR and
      simple VA tool to document numbers and causes of deaths. More work is needed to
      improve accuracy of causes of death by village headmen.

PMID- 30234091
TI  - The Evolution of Public Health Genomics: Exploring Its Past, Present, and Future.
AB  - Public health genomics has evolved to responsibly integrate advancements in
      genomics into the fields of personalized medicine and public health. Appropriate,
      effective and sustainable integration of genomics into healthcare requires an
      organized approach. This paper outlines the history that led to the emergence of
      public health genomics as a distinguishable field. In addition, a range of
      activities are described that illustrate how genomics can be incorporated into
      public health practice. Finally, it presents the evolution of public health
      genomics into the new era of "precision public health."

PMID- 30234093
TI  - Equitable Participation in Biobanks: The Risks and Benefits of a "Dynamic
      Consent" Approach.
AB  - Participation in biobanks tends to favor certain groups-white, middle-class, more
      highly-educated-often to the exclusion of others, such as indigenous people, the
      socially-disadvantaged and the culturally and linguistically diverse. Barriers to
      participation, which include age, location, cultural sensitivities around human
      tissue, and issues of literacy and language, can influence the diversity of
      samples found in biobanks. This has implications for the generalizability of
      research findings from biobanks being able to be translated into the clinic.
      Dynamic Consent, which is a digital decision-support tool, could improve
      participants' recruitment to, and engagement with, biobanks over time and help to
      overcome some of the barriers to participation. However, there are also risks
      that it may deepen the "digital divide" by favoring those with knowledge and
      access to digital technologies, with the potential to decrease participant
      engagement in research. When applying a Dynamic Consent approach in biobanking,
      researchers should give particular attention to adaptations that can improve
      participant inclusivity, and evaluate the tool empirically, with a focus on
      equity-relevant outcome measures. This may help biobanks to fulfill their promise
      of enabling translational research that is relevant to all.

PMID- 30234094
TI  - Exit-Knowledge of Ambulatory Patients About Medications Dispensed in Government
      Hospital in Eastern Ethiopia: The Need for Focused Patient Counseling.
AB  - Background: In the counseling process, a multi-cultural competence of dispenser
      is among the key factors affecting his/her successful communication with patients
      for achieving optimal use of medications. For patients to use dispensed drugs
      appropriately, it is a must for them to understand the medication related
      information provided by the dispenser. Hence, the objective of this study was to
      identify parameters that likely affect ambulatory patients' knowledge of
      medication(s) provided at the exit of outpatient pharmacy of Federal Harar Police
      Hospital, Eastern Ethiopia. Methods: Cross-sectional study design was employed to
      conduct this study. An interview of patients was made at the exit of hospital
      pharmacy using a semi-structured questionnaire. The interview tool primarily
      assessed the knowledge of the patients for a maximum of three medications
      provided. Statistical Package for Social Sciences (SPSS), Version 20.0, was
      employed for analysis of the data. Chi-squared test was done to retain parameters
      with potential to have association; and the retained parameters were adjusted by
      performing bivariate and multivariate logistic regression analyses. Results: The
      result showed that only 37.2, 33.4 and 28.7% of the patients were able to recall
      the name of the drug(s), common side effects, and actions to be taken for missed
      doses, respectively. The likelihood of patients' knowledge for dispensed
      medications was high among patients aged 19-39 years (adjusted odds ratio [AOR]:
      5.0; 95% CI: 1.04-24.2) and who thought their communication with dispenser had
      been polite (AOR: 4.62; 95% CI: 1.48-14.4). However, the knowledge status was
      found low among patients who were Afan Oromo speakers (AOR: 0.58; 95% CI: 0.35
      0.95) and who came from rural residence (AOR: 0.48; 95% CI: 0.25-0.90).
      Conclusion: A high proportion of patients were unable to recall the drug (s)
      name, associated common toxicities, and actions to be taken in case of missed
      dose. In addition, patients who were at early adulthood and who were positive for
      the politeness of dispenser had better exit-knowledge of their medication.
      Therefore, for the patients' clear understanding of medications provided, it is
      mandatory to optimize patient-dispenser communication possibly by adapting multi
      cultural communication skills and by providing focused training for dispensers to
      address factors that likely affect patient-dispenser interactions.

PMID- 30234095
TI  - The Importance of Relevance: Willingness to Share eHealth Data for Family
      Medicine Research.
AB  - Objective: To determine the proportion of family medicine patients unwilling to
      allow their eHealth data to be used for research purposes, and evaluate how
      patient characteristics and the relevance of research impact that decision.
      Design: Cross-sectional questionnaire. Setting: Acute care respiratory clinic or
      an outpatient family medicine clinic in Montreal, Quebec. Participants: Four
      hundred seventy-four waiting room patients recruited via convenience sampling.
      Main Outcome Measures: A self-administered questionnaire collected data on age,
      gender, employment status, education, mother tongue and perceived health status.
      The main outcome of was self-reported relevance of three research scenarios and
      willingness or refusal to share their anonymized data. Responses were compared
      for family practice vs. specialty care patients. Results: The questionnaire was
      completed by 229 family medicine respondents and 245 outpatient respondents.
      Almost a quarter of all respondents felt the research was not relevant. Family
      medicine patients (15.7%) were unwilling to allow their data to be used for at
      least one scenario vs. 9.4% in the outpatient clinic. Lack of relevance (OR
      11.55; 95% CI 5.12-26.09) and being in family practice (OR 2.13; 95% CI 1.06
      4.27) increased the likelihood of refusal to share data for research. Conclusion:
      Family medicine patients were somewhat less willing to share eHealth data, but
      the overall refusal rate indicates a need to better engage patients in
      understanding the significance of full access to eHealth data for the purposes of
      research. Personal relevance of the research had a strong impact on the responses
      arguing for better efforts to make research more pertinent to patients.

PMID- 30234096
TI  - Electron Acceptors With a Truxene Core and Perylene Diimide Branches for Organic
      Solar Cells: The Effect of Ring-Fusion.
AB  - In this work, a star-shaped planar acceptor named FTr-3PDI was synthesized via
      ring-fusion between truxene core and three bay-linked perylene diimide (PDI)
      branches. Compared to the unfused non-planar acceptor Tr-3PDI, FTr-3PDI exhibits
      better structural rigidity and planarity, as well as more effective conjugation
      between truxene core and PDI branches. As a result, FTr-3PDI shows up-shifted
      energy levels, enhanced light absorption coefficient, increased electron
      mobility, and more favorable phase separation morphology in bulk-heterojunction
      (BHJ) blend films as compared to Tr-3PDI. Consequently, FTr-3PDI afforded higher
      power conversion efficiency (PCE) in BHJ solar cells when blended with a polymer
      donor PTB7-Th. This work demonstrates that ring-fusion is a promising molecular
      design strategy to combine the merits of truxene and PDI for non-fullerene
      acceptors used in organic solar cells.

PMID- 30234097
TI  - Activated Amorphous Carbon With High-Porosity Derived From Camellia Pollen Grains
      as Anode Materials for Lithium/Sodium Ion Batteries.
AB  - Carbonaceous anode materials are commonly utilized in the energy storage systems,
      while their unsatisfied electrochemical performances hardly meet the increasing
      requirements for advanced anode materials. Here, activated amorphous carbon (AAC)
      is synthesized by carbonizing renewable camellia pollen grains with naturally
      hierarchical structure, which not only maintains abundant micro- and mesopores
      with surprising specific surface area (660 m2 g-1), but also enlarges the
      interlayer spacing from 0.352 to 0.4 nm, effectively facilitating ions transport,
      intercalation, and adsorption. Benefiting from such unique characteristic, AAC
      exhibits 691.7 mAh g-1 after 1200 cycles at 2 A g-1, and achieves 459.7, 335.4,
      288.7, 251.7, and 213.5 mAh g-1 at 0.1, 0.5, 1, 2, 5 A g-1 in rate response for
      lithium-ion batteries (LIBs). Additionally, reversible capacities of 324.8,
      321.6, 312.1, 298.9, 282.3, 272.4 mAh g-1 at various rates of 0.1, 0.2, 0.5, 1,
      2, 5 A g-1 are preserved for sodium-ion batteries (SIBs). The results reveal that
      the AAC anode derived from camellia pollen grains can display excellent cyclic
      life and superior rate performances, endowing the infinite potential to extend
      its applications in LIBs and SIBs.

PMID- 30234098
TI  - Design, Synthesis and Biological Activity Evaluation of S-Substituted 1H-5
      Mercapto-1,2,4-Triazole Derivatives as Antiproliferative Agents in Colorectal
      Cancer.
AB  - Colon cancer is a widespread pathology with complex biochemical etiology based on
      a significant number of intracellular signaling pathways that play important
      roles in carcinogenesis, tumor proliferation and metastasis. These pathways
      function due to the action of key enzymes that can be used as targets for new
      anticancer drug development. Herein we report the synthesis and biological
      antiproliferative evaluation of a series of novel S-substituted 1H-3-R-5-mercapto
      1,2,4-triazoles, on a colorectal cancer cell line, HT-29. Synthesized compounds
      were designed by docking based virtual screening (DBVS) of a previous constructed
      compound library against protein targets, known for their important role in
      colorectal cancer signaling: MEK1, ERK2, PDK1, VEGFR2. Among all synthesized
      structures, TZ55.7, which was retained as a possible PDK1 (phospholipid-dependent
      kinase 1) inhibitor, exhibited the most significant cytotoxic activity against HT
      29 tumor cell line. The same compound alongside other two, TZ53.7 and TZ3a.7, led
      to a significant cell cycle arrest in both sub G0/G1 and G0/G1 phase. This study
      provides future perspectives for the development of new agents containing the
      1,2,4-mercapto triazole scaffold with antiproliferative activities in colorectal
      cancer.

PMID- 30234100
TI  - Kinetics of Photocatalyzed Reactions: Five Lessons Learned.
AB  - Elucidation of kinetics of photocatalyzed chemical mechanisms occurring at
      interfaces (gas-solid, liquid-solid) has been challenging. We summarize here five
      lessons learned over five decades. 1. An assumed reaction network leads to a
      single kinetic model, but a common model, the Langmuir-Hinshelwood rate equation,
      r = kcat K C/ [1 +KC], arises from multiple mechanisms, hence models alone do not
      reveal unique mechanisms. 2. The Langmuir-Hinshelwood model parameter kcat
      represents the slow step at a catalyst surface, and in thermal catalysis, depends
      upon the reactant structure. However, early photocatalysis work with light
      chlorinated hydrocarbons in aqueous solutions showed a single kcat value,
      independent of reactant structure. 3. The dependence of the Langmuir-Hinshelwood
      parameters, kcat and K, upon intensity indicates that a pseudo-steady state
      approach is more fundamental than the presumed equilibrated adsorption of the LH
      model. 4. Dyes and phenols are commonly studied, and claimed as first order
      reactions, despite often exhibiting rate constants which diminish with increasing
      contaminant concentration. We show that such studies are the result of intrinsic
      zero order data plotted on a semilog graph, and involve zero order rate
      limitation by reactant saturation, electron transfer to O2, oxygen mass transfer,
      or light supply. 5. The apparent kinetics for contaminant removal from
      photocatalytic self-cleaning surfaces depends upon multiple circumstances,
      including the geometry of reactant deposit, catalyst porosity, and reactant light
      absorption. A single decision table suffices to indicate the apparent reaction
      order, n, to assume when fitting photocatalytic kinetic data from self-cleaning
      surfaces to a power law rate form, rate = k Cn.

PMID- 30234099
TI  - Relevance of Copper and Organic Cation Transporters in the Activity and Transport
      Mechanisms of an Anticancer Cyclometallated Gold(III) Compound in Comparison to
      Cisplatin.
AB  - The molecular mechanisms of toxicity and cellular transport of anticancer
      metallodrugs, including platinum-based agents, have not yet been fully
      elucidated. The aim of our study was to investigate the relevance of copper
      transporters (CTR1 and ATP7A/B), organic cation transporters (OCT2) and the
      multidrug and toxin extrusion proteins (MATE) in the intracellular accumulation
      of a novel organometallic cytotoxic Au(III) compound in cancer cells in
      comparison to cisplatin. Specifically, the synthesis and characterization of the
      gold complex [Au(pyb-H)(PPh2Ar)Cl]PF6 (PPh2Ar = 3-[4-(diphenylphosphino)phenyl]-7
      methoxy-2H-chromen-2-one] (1), featuring a coumarin ligand endowed with "smart"
      fluorescence properties, have been achieved. Initially, the cytotoxic effects of
      both cisplatin and 1 were studied in a small panel of human cancer cells, and
      against a non-tumorigenic cell line in vitro. Thus, the human ovarian cancer cell
      line A2780 and its cisplatin resistant variant A2780cisR, were selected, being
      most sensitive to the treatment of the gold complex. Co-incubation of the
      metallodrugs with CuCl2 (a CTR1 substrate) increased the cytotoxic effects of
      both the Au(III) complex and cisplatin; while co-incubation with cimetidine
      (inhibitor of OCT2 and MATE) showed some effect only after 72 h incubation. ICP
      MS (Inductively Coupled Plasma Mass Spectrometry) analysis of the cell extracts
      showed that co-incubation with CuCl2 increases Au and Cu accumulation in both
      cancer cell lines, in accordance with the enhanced antiproliferative effects.
      Conversely, for cisplatin, no increase in Pt content could be observed in both
      cell lines after co-incubation with either CuCl2 or cimetidine, excluding the
      involvement of CTR1, OCT2, and MATE in drug accumulation and overall anticancer
      effects. This result, together with the evidence for increased Cu content in
      A2780 cells after cisplatin co-treatment with CuCl2, suggests that copper
      accumulation is the reason for the observed enhanced anticancer effects in this
      cell line. Moreover, metal uptake studies in the same cell lines indicate that
      both 1 and cisplatin are not transported intracellularly by CTR1 and OCT2.
      Finally, preliminary fluorescence microscopy studies enabled the visualization of
      the sub-cellular distribution of the gold compound in A2780 cells, suggesting
      accumulation in specific cytosolic components/organelles.

PMID- 30234101
TI  - Collagen Partition in Polymeric Aqueous Two-Phase Systems for Tissue Engineering.
AB  - Aqueous two-phase systems (ATPS) of polyethylene glycol (PEG) and dextran (DEX)
      are commonly used to partition proteins. Protein partition in ATPS is a complex
      phenomenon and depends on factors including molecular weight of polymers, and
      electrochemical and ionic properties of the phases. We studied the effect of
      polymer molecular weight on the partition of a natural protein, collagen, in
      several ATPS formulations made with non-ionic polymers polyethylene glycol (PEG)
      and dextran (DEX). We found that partitioning of collagen to an aqueous phase
      significantly increases when the molecular weight of the corresponding phase
      polymer decreases. Additionally, a large difference between the molecular weight
      of the phase-forming polymers was necessary to cause a significant uneven
      collagen distribution between the aqueous phases. We then employed one of the
      systems to create a three-dimensional breast cancer microtissue by entrapping a
      spheroid of breast cancer cells within the partitioned collagen. This convenient
      technique to generate 3D microtissues offers a convenient and promising approach
      for tissue engineering applications.

PMID- 30234102
TI  - Fluorination Induced Donor to Acceptor Transformation in A1-D-A2-D-A1-Type
      Photovoltaic Small Molecules.
AB  - With the development of diversity of non-fullerene acceptors, it is found that
      there is no clear boundary between electron donors and electron acceptors.
      Modulation of the electron donating and withdrawing properties of organic
      semiconductors is necessary for organic photovoltaics research. In this work, we
      designed and synthesized three A1-D-A2-D-A1-type (A represents acceptor unit and
      D represents donor unit) small molecules, named as M-0F, M-1F, and M-2F,
      respectively containing zero, one, and two fluorine atoms in the terminal
      acceptor segments (A1), respectively. Fluorination substitution was found to be
      able to downshift the HOMO and LUMO energy level, red-shift the absorption, and
      enhance the electron mobility. The M-0F exhibited the highest efficiency of 5.99%
      as a donor in fullerene-containing system and the lowest efficiency of 0.58% as
      an acceptor in fullerene-free system. While the M-2F performed the lowest
      efficiency of 0.97% as the donor and the highest efficiency of 2.65% as the
      acceptor. The electron-donating and electron-withdrawing property of M-1F are in
      between that of M-0F and M-2F. Among the three molecules, the electron mobility
      is increased while the hole mobility is decreased with increasing fluorination.
      This work provides a typical example of tuning of the electron donating and
      withdrawing property without changes to the backbone of the conjugated molecules,
      which is important for further designing high performance solution processable
      small molecules.

PMID- 30234103
TI  - Synthesis and Characterization of Oligothiophene-Porphyrin-Based Molecules That
      Can Be Utilized for Optical Assignment of Aggregated Amyloid-beta Morphotypes.
AB  - Molecular tools for fluorescent imaging of protein aggregates are essential for
      understanding the significance of these pathological hallmarks in proteopathic
      neurodegenerative diseases, such as Alzheimer's disease. Here, we report the
      synthesis of a series of oligothiophene porphyrin hybrids, OTPHs, and the
      evaluation of these dyes for fluorescent imaging of beta-amyloid aggregates in
      tissue sections from a transgenic mouse model with Alzheimer's disease pathology.
      The OTPHs proved to be successful for spectral and lifetime imaging assessment of
      protein deposits and our findings confirm that the enhanced spectral range and
      distinct lifetime diversity of these novel tools allow a more precise assessment
      of heterogeneous amyloid morphology compared with the corresponding
      oligothiophene dye. In addition, the chemical identity of the porphyrin moiety,
      as well as the spacing between the two optical active moieties, influenced the
      OTPHs performance for fluorescent assignment of the protein deposits. We foresee
      that our findings will aid in the chemical design of dyes that can be utilized as
      optical tools for studying the polymorphic nature of protein aggregates
      associated with proteopathic neurodegenerative diseases.

PMID- 30234104
TI  - Talaropeptides A-D: Structure and Biosynthesis of Extensively N-methylated Linear
      Peptides From an Australian Marine Tunicate-Derived Talaromyces sp.
AB  - An Australian marine tunicate-derived fungus, Talaromyces sp. CMB-TU011 was
      subjected to a program of analytical microbioreactor (MATRIX) cultivations,
      supported by UHPLC-QTOF profiling, to reveal conditions for producing a new class
      of extensively N-methylated 11-12 residue linear peptides, talaropeptides A-D (2
      5). The structures for 2-5, inclusive of absolute configurations, were determined
      by a combination of detailed spectroscopic and chemical (e.g., C3 and C18
      Marfey's) analyses. We report on the biological properties of 2-5, including
      plasma stability, as well as antibacterial, antifungal and cell cytotoxicity. The
      talaropeptide mega non-ribosomal peptide synthetase (NRPS) is described, as
      second only in size to that for the fungus-derived immunosuppressant cyclosporine
      (an 11-residue extensively N-methylated cyclic peptide).

PMID- 30234105
TI  - Resource Recovery Potential From Lignocellulosic Feedstock Upon Lysis With Ionic
      Liquids.
AB  - Lignocellulosic residues from energy crops offer a high potential to recover
      bioproducts and biofuels that can be used as raw matter for agriculture
      activities within a circular economy framework. Anaerobic digestion (AD) is a
      well-established driver to convert these residues into energy and bioproducts.
      However, AD of lignocellulosic matter is slow and yields low methane potential,
      and therefore several pre-treatment methods have been proposed to increase the
      energy yield of this process. Hereby, we have assessed the pre-treatment of
      lignocellulosic biomass (barley straw) with the ionic liquid (IL) 1-ethyl-3
      methylimidazolium acetate and its effect on the biochemical methane potential
      (BMP). The BMP of the residue was evaluated at different inoculum to substrate
      (I/S) ratios and working under meso and thermophilic conditions. Solids
      destruction upon AD is highly enhanced by the IL-pretreatment. This also resulted
      in a higher BMP, both in mesophilic as well as thermophilic conditions. At the
      optimum I/S ratio of 2:1 (dried weight, dw), the BMP of the IL-pre-treated
      feedstock increased 28 and 80% for 35 days of thermophilic and mesophilic AD,
      respectively, as compared to the fresh feedstock, achieving values of 364 and 412
      LCH4/kgTS. We also explored the effect of this pretreatment on the phosphorus
      recovery potential from the digestate upon release from the AD process.
      Thermophilic anaerobic digestion of IL-pre-treated biomass provided the highest P
      recovery potential from lignocellulosic residues (close to 100% of the
      theoretical P content of the lignocellulosic feedstock). Therefore, the
      pretreatment of lignocellulosic feedstock with IL before AD is a promising
      platform to obtain bioenergy and recover P to be regained for the agriculture
      sector.

PMID- 30234107
TI  - CRISPR Gene Perturbations Provide Insights for Improving Bacterial Biofuel
      Tolerance.
AB  - Economically-viable biofuel production is often limited by low levels of
      microbial tolerance to high biofuel concentrations. Here we demonstrate the first
      application of deactivated CRISPR perturbations of gene expression to improve
      Escherichia coli biofuel tolerance. We construct a library of 31 unique CRISPR
      inhibitions and activations of gene expression in E. coli and explore their
      impacts on growth during 10 days of exposure to n-butanol and n-hexane. We show
      that perturbation of metabolism and membrane-related genes induces the greatest
      impacts on growth in n-butanol, as does perturbation of redox-related genes in n
      hexanes. We identify uncharacterized genes yjjZ and yehS with strong potential
      for improving tolerance to both biofuels. Perturbations demonstrated significant
      temporal dependencies, suggesting that rationally designing time-sensitive gene
      circuits can optimize tolerance. We also introduce a sgRNA-specific hyper-mutator
      phenotype (~2,600-fold increase) into our perturbation strains using error-prone
      Pol1. We show that despite this change, strains exhibited similar growth
      phenotypes in n-butanol as before, demonstrating the robustness of CRISPR
      perturbations during prolonged use. Collectively, these results demonstrate the
      potential of CRISPR manipulation of gene expression for improving biofuel
      tolerance and provide constructive starting points for optimization of biofuel
      producing microorganisms.

PMID- 30234106
TI  - In vitro Models and On-Chip Systems: Biomaterial Interaction Studies With Tissues
      Generated Using Lung Epithelial and Liver Metabolic Cell Lines.
AB  - In vitro models are very important in medicine and biology, because they provide
      an insight into cells' and microorganisms' behavior. Since these cells and
      microorganisms are isolated from their natural environment, these models may not
      completely or precisely predict the effects on the entire organism. Improvement
      in this area is secured by organ-on-a-chip development. The organ-on-a-chip
      assumes cells cultured in a microfluidic chip. The chip simulates bioactivities,
      mechanics and physiological behavior of organs or organ systems, generating
      artificial organs in that way. There are several cell lines used so far for each
      tested artificial organ. For lungs, mostly used cell lines are 16HBE, A549, Calu
      3, NHBE, while mostly used cell lines for liver are HepG2, Hep 3B, TPH1, etc. In
      this paper, state of the art for lung and liver organ-on-a-chip is presented,
      together with the established in vitro testing on lung and liver cell lines, with
      the emphasis on Calu-3 (for lung cell lines) and Hep-G2 (for liver cell lines).
      Primary focus in this review is to discuss different researches on the topics of
      lung and liver cell line models, approaches in determining fate and transport,
      cell partitioning, cell growth and division, as well as cell dynamics, meaning
      toxicity and effects. The review is finalized with current research gaps and
      problems, stating potential future developments in the field.

PMID- 30234108
TI  - Aberrations of DNA Repair Pathways in Prostate Cancer: Future Implications for
      Clinical Practice?
AB  - Patients who are carriers of inherited mutations in essential component of DNA
      repair pathways have a significantly higher lifetime risk for developing cancer
      compared to the population of reference. Recent advances in DNA next-generation
      sequencing technology have allowed screening for carriers of those mutations,
      allowing development of promising risk-reduction strategies and providing the
      rationale to personalize the therapeutic approach for these patients. New
      intriguing scenarios are opening nowadays for the management of prostate cancer
      in patients with germline or somatic mutations in components of DNA repair
      pathways (e.g., BRCA1 and BRCA2 genes), such as specific screening policies and
      new therapeutic strategies involving PARP inhibitors or platinum-based
      chemotherapy.

PMID- 30234109
TI  - The Human SLC1A5 (ASCT2) Amino Acid Transporter: From Function to Structure and
      Role in Cell Biology.
AB  - SLC1A5, known as ASCT2, is a neutral amino acid transporter belonging to the SLC1
      family and localized in the plasma membrane of several body districts. ASCT2 is
      an acronym standing for Alanine, Serine, Cysteine Transporter 2 even if the
      preferred substrate is the conditionally essential amino acid glutamine, with
      cysteine being a modulator and not a substrate. The studies around amino acid
      transport in cells and tissues began in the '60s by using radiolabeled compounds
      and competition assays. After identification of murine and human genes, the
      function of the coded protein has been studied in cell system and in
      proteoliposomes revealing that this transporter is a Na+ dependent antiporter of
      neutral amino acids, some of which are only inwardly transported and others are
      bi-directionally exchanged. The functional asymmetry merged with the kinetic
      asymmetry in line with the physiological role of amino acid pool harmonization.
      An intriguing function has been described for ASCT2 that is exploited as a
      receptor by a group of retroviruses to infect human cells. Interactions with
      scaffold proteins and post-translational modifications regulate ASCT2 stability,
      trafficking and transport activity. Two asparagine residues, namely N163 and
      N212, are the sites of glycosylation that is responsible for the definitive
      localization into the plasma membrane. ASCT2 expression increases in highly
      proliferative cells such as inflammatory and stem cells to fulfill the augmented
      glutamine demand. Interestingly, for the same reason, the expression of ASCT2 is
      greatly enhanced in many human cancers. This finding has generated interest in
      its candidacy as a pharmacological target for new anticancer drugs. The recently
      solved 3D structure of ASCT2 will aid in the rational design of such therapeutic
      compounds.

PMID- 30234110
TI  - Two Tier Hox Collinearity Mediates Vertebrate Axial Patterning.
AB  - A two tier mechanism mediates Hox collinearity. Besides the familiar collinear
      chromatin modification within each Hox cluster (nanocollinearity), there is also
      a macrocollinearity tier. Individual Hox clusters and individual cells are
      coordinated and synchronized to generate multiscale (macro and nano) collinearity
      in the early vertebrate embryo. Macro-collinearity is mediated by three non-cell
      autonomous Hox-Hox interactions. These mediate temporal collinearity in early NOM
      (non-organizer mesoderm), time space translation where temporal collinearity is
      translated to spatial collinearity along the early embryo's main body axis and
      neural transformation, where Hox expression is copied monospecifically from NOM
      mesoderm to overlying neurectoderm in the late gastrula. Unlike nanocollinearity,
      which is Hox cluster restricted, axial macrocollinearity extends into the head
      and EAD domains, thus covering the whole embryonic anterior-posterior (A-P) axis.
      EAD: extreme anterior domain, the only A-P axial domain anterior to the head. The
      whole time space translation mechanism interacts with A-P signaling pathways via
      "decision points," separating different domains on the axis.

PMID- 30234111
TI  - MyD88 Regulates the Expression of SMAD4 and the Iron Regulatory Hormone Hepcidin.
AB  - The myeloid differentiation primary response gene 88 (MyD88) is an adaptive
      protein that is essential for the induction of inflammatory cytokines through
      almost all the Toll-like receptors (TLRs). TLRs recognize molecular patterns
      present in microorganisms called pathogen-associated molecular patterns.
      Therefore, MyD88 plays an important role in innate immunity since its activation
      triggers the first line of defense against microorganisms. Herein, we describe
      the first reported role of MyD88 in an interconnection between innate immunity
      and the iron-sensing pathway (BMP/SMAD4). We found that direct interaction of
      MyD88 with SMAD4 protein activated hepcidin expression. The iron regulatory
      hormone hepcidin is indispensable for the intestinal regulation of iron
      absorption and iron recycling by macrophages. We show that MyD88 induces hepcidin
      expression in a manner dependent on the proximal BMP responsive element on the
      hepcidin gene (HAMP) promoter. We identified the Toll/interleukin-1 receptor
      (TIR) domain of MyD88 as the domain of interaction with SMAD4. Furthermore, we
      show that BMP6 stimulation, which activates SMAD6 expression, also induces MyD88
      proteosomal degradation as a negative feedback mechanism to limit hepcidin
      induction. Finally, we report that the MyD88 gain-of-function L265P mutation,
      frequently encountered in B-cell lymphomas such as Waldenstrom's
      macroglobulinemia, enhances hepcidin expression and iron accumulation in B cell
      lines. Our results reveal a new potential role for MyD88 in the SMAD signaling
      pathway and iron homeostasis regulation.

PMID- 30234112
TI  - Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived
      Neurotrophic Factor Antagonizes Programmed Cell Death.
AB  - Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a potent survival
      promoting protein with neurorestorative effect for neurodegenerative diseases.
      Its mechanism of action, albeit poorly known, depends strongly on the CXXC motif
      (CKGC). Here we studied the survival-promoting properties of the CKGC
      tetrapeptide from MANF. In the Jurkat T lymphocytic cell line, CKGC potently
      inhibits death receptor Fas-induced apoptosis and mildly counteracts
      mitochondrial apoptosis and necroptosis. The peptide with serines instead of
      cysteines (SKGS) has no survival-promoting activity. The cytoprotective
      efficiency of the peptide against Fas-induced apoptosis is significantly improved
      by reduction of its cysteines by dithiotreitol, suggesting that it protects the
      cells via cysteine thiol groups, partially as an antioxidant. CKGC neutralizes
      the reactive oxygen species, maintains the mitochondrial membrane potential and
      prevents activation of the effector caspases in the Jurkat cells with activated
      Fas. The peptide does not require intracellular administration, as it is
      endocytosed and resides mainly in the Golgi. Finally, the peptide also potently
      promotes survival of cultured primary dopaminergic neurons.

PMID- 30234113
TI  - Experimental Considerations for Single-Cell RNA Sequencing Approaches.
AB  - Single-cell transcriptomic technologies have emerged as powerful tools to explore
      cellular heterogeneity at the resolution of individual cells. Previous scientific
      knowledge in cell biology is largely limited to data generated by bulk profiling
      methods, which only provide averaged read-outs that generally mask cellular
      heterogeneity. This averaged approach is particularly problematic when the
      biological effect of interest is limited to only a subpopulation of cells such as
      stem/progenitor cells within a given tissue, or immune cell subsets infiltrating
      a tumor. Great advances in single-cell RNA sequencing (scRNAseq) enabled
      scientists to overcome this limitation and allow for in depth interrogation of
      previously unexplored rare cell types. Due to the high sensitivity of scRNAseq,
      adequate attention must be put into experimental setup and execution. Careful
      handling and processing of cells for scRNAseq is critical to preserve the native
      expression profile that will ensure meaningful analysis and conclusions. Here, we
      delineate the individual steps of a typical single-cell analysis workflow from
      tissue procurement, cell preparation, to platform selection and data analysis,
      and we discuss critical challenges in each of these steps, which will serve as a
      helpful guide to navigate the complex field of single-cell sequencing.

PMID- 30234115
TI  - Tumor Heterogeneity in Primary Colorectal Cancer and Corresponding Metastases.
      Does the Apple Fall Far From the Tree?
AB  - Colorectal cancer harbors tremendous heterogeneity, with temporal and spatial
      differences in genetic mutations, epigenetic regulation, and tumor
      microenvironment. Analyzing the distribution and frequency of genetic,
      epigenetic, and microenvironment differences within a given tumor and between
      different sites of a metastatic tumor has been used as a powerful tool to
      investigate tumorigenesis, tumor progression, and to yield insight into various
      models of tumor development. A better understanding of tumor heterogeneity would
      have tremendous clinical relevance, which may manifest most clearly when genetic
      analyses to inform treatment decisions are performed on a very limited sample of
      a large tumor. This review summarizes the current concepts of tumor
      heterogeneity, with a focus on primary colorectal cancers and their corresponding
      metastases as well as potential clinical implications.

PMID- 30234117
TI  - Editorial: Pathogenic Advances and Therapeutic Perspectives for Eosinophilic
      Inflammation.

PMID- 30234116
TI  - Comorbidities and Treatment Strategies in Bullous Pemphigoid: An Appraisal of the
      Existing Litterature.
AB  - Bullous Pemphigoid is an autoimmune skin blistering disease. It is caused by
      deposition of auto antibodies along the dermal-epidermal border leading to
      inflammation. The antibodies are directed against anchoring filaments in the
      epidermis, but these antigens are also present in the neurological tissues and
      this has led to speculation of an association between multiple sclerosis and
      bullous pemphigoid. Additionally recent epidemiological studies have pointed at
      an increased risk of cardio-vascualr diseases and an increased moratality among
      the patients with bullous pemphigoid. In this mini review we present the recent
      findings in this area and as well as the treatment strategies when comorbidities
      are taken into consideration.

PMID- 30234114
TI  - Autophagy in Neutrophils: From Granulopoiesis to Neutrophil Extracellular Traps.
AB  - Autophagy is an evolutionarily conserved intracellular degradation system aiming
      to maintain cell homeostasis in response to cellular stress. At physiological
      states, basal or constitutive level of autophagy activity is usually low;
      however, it is markedly up-regulated in response to oxidative stress, nutrient
      starvation, and various immunological stimuli including pathogens. Many studies
      over the last years have indicated the implication of autophagy in a plethora of
      cell populations and functions. In this review, we focus on the role of autophagy
      in the biology of neutrophils. Early studies provided a link between autophagy
      and neutrophil cell death, a process essential for resolution of inflammation.
      Since then, several lines of evidence both in the human system and in murine
      models propose a critical role for autophagy in neutrophil-driven inflammation
      and defense against pathogens. Autophagy is essential for major neutrophil
      functions, including degranulation, reactive oxygen species production, and
      release of neutrophil extracellular traps. Going back to neutrophil generation in
      the bone marrow, autophagy plays a critical role in myelopoiesis, driving the
      differentiation of progenitor cells of the myeloid lineage toward neutrophils.
      Taken together, in this review we discuss the functional role of autophagy in
      neutrophils throughout their life, from their production in the bone marrow to
      inflammatory responses and NETotic cell death.

PMID- 30234118
TI  - Remini-Sing: A Feasibility Study of Therapeutic Group Singing to Support
      Relationship Quality and Wellbeing for Community-Dwelling People Living With
      Dementia and Their Family Caregivers.
AB  - Background: Living at home following a diagnosis of dementia can be difficult for
      both the person living with dementia (PwD) and their family caregivers (FCG).
      Active group music participation may provide an avenue for emotional release,
      offer psychosocial support to caregivers and stimulate meaningful interaction
      between caregivers and loved ones with dementia. Therapeutic music interventions
      also have the capacity to facilitate reminiscence and social engagement and can
      help to manage challenging symptoms associated with dementia, such as anxiety,
      apathy, and agitation. Method: This feasibility study examined the acceptability
      of a 20-week therapeutic group singing intervention (Remini-Sing) and
      quantitative research assessments for PwD/FCG dyads living in the community.
      Quantitative measures for the following outcomes were tested for sensitivity and
      acceptability: relationship quality (PwD and FCG); life satisfaction, caregiver
      satisfaction, flourishing, and depression for FCGs; and anxiety, apathy,
      agitation, and quality of life for PwD. Quantitative assessments were conducted
      before, during (midway) and after 20 weeks of participation in a therapeutic
      singing group attended by the PwD and FCG together. The Remini-Sing intervention
      incorporated vocal warm ups, singing familiar songs, learning new songs, and
      opportunities for social interaction. Qualitative interviews were conducted with
      all dyads that completed the intervention. Results: Twelve PWD/FCG dyads were
      recruited and enrolled in the study. High participation and retention rates
      indicated that the intervention was received favorably by participants. There
      were no statistically significant changes on measures from pre to post
      intervention. However, favorable baseline scores on relationship quality and
      wellbeing measures were sustained over the 20-week intervention. The testing of
      these measures for feasibility also revealed that some were too difficult for PwD
      and thus yielded questionable results, some were potentially less relevant, and
      there were likely floor and ceiling effects on several of the measures utilized.
      Conclusions: This study demonstrated good feasibility for a research protocol and
      therapeutic group singing intervention for community-dwelling PwD and their FCGs.
      Participant reflections and researcher observations yielded useful information
      guiding the selection of quantitative outcome measures for future research in
      this area.

PMID- 30234120
TI  - Improvement in Frailty in a Patient With Severe Chronic Obstructive Pulmonary
      Disease After Ninjin'yoeito Therapy: A Case Report.
AB  - Frailty is a poor prognostic factor in patients with chronic obstructive
      pulmonary disease (COPD). Although various studies have assessed the effects of
      conventional treatment with bronchodilators, nutritional support, and pulmonary
      rehabilitation for frailty in patients with COPD, none have addressed the effects
      of traditional Japanese medicine (Kampo medicine). Herein, we report the
      successful management of frailty using Ninjin'yoeito therapy in a 76-year-old
      patient with COPD. Despite being prescribed multiple bronchodilators, nutritional
      supplement therapy, patient education, and pulmonary rehabilitation, the patient
      exhibited unintentional weight loss, low energy, and low physical activity.
      Ninjin'yoeito was prescribed and these subjective symptoms began to improve 1
      month after treatment initiation. In 6 months, the patient reported no frailty,
      had increased muscle mass, and had achieved an almost normal healthy state.
      Ninjin'yoeito has been associated with both physical effects, such as improvement
      in overall physical strength and appetite, and reduction in fatigue, and
      psychological effects, such as greater motivation and reduction of depression and
      anxiety symptoms. Physicians have usually treated COPD primarily with organ
      specific treatments, such as bronchodilators; however, addressing both the
      physiological and psychological vulnerability has been difficult. This case
      report illustrates the potential usefulness of Ninjin'yoeito treatment for
      frailty in patients with COPD.

PMID- 30234119
TI  - An Update on Breast Cancer Multigene Prognostic Tests-Emergent Clinical
      Biomarkers.
AB  - Multigene signatures generate crucial prognostic information particularly useful
      for cancer patients where clinical parameters and traditional immunohistochemical
      markers alone lead to equivocal prognosis. Clinicians are now provided with
      molecular tools that assist in the outline of adjuvant therapies, namely helping
      decide on the extension of adjuvant endocrine therapy or on suppressing adjuvant
      chemotherapy in patients were toxic effects are particularly deleterious or when
      this treatment is fundamentally not needed. The importance of cancer multigene
      prognostic signatures is well elucidated in the guidelines for adjuvant systemic
      therapy in early-stage breast cancer and the guidelines on disease staging that
      are progressively integrating gene expression assays as classification
      biomarkers. In addition to the predictive and prognostic value, some genetic
      tests provide intrinsic subtyping classification. Herewith, we compare the
      molecular tests OncotypeDX, MammaPrint, Prosigna, EndoPredict, Breast Cancer
      Index, Mammostrat, and IHC4 and report the eligibility of each one in the
      suitable setting. Through to now, there is not a commercially available multigene
      test that makes recommendations regarding adjuvant treatment for HER-2 and triple
      negative breast cancers. Thus, these patients still receive adjuvant
      chemotherapy. Importantly, triple negative carcinomas are very heterogeneous
      regarding prognosis and new molecular signatures that decipher this very
      heterogeneous subgroup of breast cancer may improve the clinical management of
      the disease.

PMID- 30234121
TI  - Best Practices for Handling and Administration of Expressed Human Milk and Donor
      Human Milk for Hospitalized Preterm Infants.
AB  - The importance of human milk for the preterm infant is well established (1-3).
      However, the feeding of human milk to preterm infants is typically much more
      complicated than the mere act of breastfeeding (3, 4). The limited oral feeding
      skills of many preterm infants often results in human milk being administered via
      an enteral feeding tube (4). In addition, fortification is commonly required to
      promote optimal growth and development-particularly in the smallest of preterm
      infants (2, 4, 5). Consequently, a mother's own milk must be pumped, labeled,
      transported to the hospital, stored, tracked for appropriate expiration dates and
      times, thawed (if previously frozen), fortified, and administered to the infant
      with care taken at each step of the process to avoid microbial contamination,
      misadministration (the wrong milk for the wrong patient), fortification errors,
      and waste (1-5). Furthermore, the use of pasteurized donor human milk (DHM) for
      preterm infants when a mother's own milk is not available has been endorsed by
      many organizations (1). Therefore, appropriate procurement, storage, thawing (if
      received frozen), fortification, labeling, and administration must occur with the
      same considerations of preventing contamination and fortification errors while
      ensuring the correctly prepared final product reaches the correct patient (1).
      Many professional organizations have published best practices to provide
      hospitals with guidelines for the safe and accurate handling and preparation of
      expressed human milk (EHM) and DHM feedings for preterm infants (1-5). These best
      practices emphasize the importance of preparation location, trained staff, proper
      identification of human milk to prevent misadministration, and strategies to
      prevent fortification errors (1-6). The purpose of this mini-review article is to
      summarize current published best practices for the handling of human milk for
      preterm infants within the hospital setting (1-6). Emphasis will focus on the use
      of aseptic technique with proper sanitation and holding times/temperatures to
      limit microbial growth; use of technology to prevent misadministration of human
      milk and fortification errors as well as for tracking of expiration dates/times
      and lot numbers; and workflow strategies to promote safety while improving
      efficiencies (1-7).

PMID- 30234123
TI  - Feed Choice Led to Higher Protein Intake in Broiler Chickens Experimentally
      Infected With Campylobacter jejuni.
AB  - In 2016, Campylobacter was the most commonly reported gastrointestinal bacterial
      pathogen in humans in the European Union with 246,307 reported cases. Of these
      cases, 83.6% were Campylobacter jejuni. The objective of the present study was to
      investigate to what extent an infection with C. jejuni alters the feed intake
      behavior of broiler chicks in terms of protein intake. This was done to see if,
      conversely, measures of control could be derived. In total, 300 commercial
      broilers of the Ross 308 line were allocated to four different groups, including
      five replications of 15 chickens each. In two groups, a conventional diet [216 g
      CP/kg dry matter (DM)] and in the two choice diet groups, diets with different
      levels of crude protein (286 and 109 g CP/kg DM, respectively) were fed between
      day 14 and day 42. An intake of both choice diets at a ratio of 3:2 resulted in a
      composition of consumed feed identical to that of the control concerning
      composition, energy and nutrient content. One group of each feeding concept was
      infected artificially with C. jejuni at day 21 by applying an oral C. jejuni
      suspension containing 5.26 +/- 0.08 log10 colony forming units of C. jejuni to
      three out of 15 chickens. No significant differences concerning C. jejuni
      prevalence and excretion could be seen. Broilers infected with C. jejuni chose a
      higher amount of the high protein choice diet in comparison to C. jejuni negative
      broilers. This resulted in a significantly (p < 0.0001) higher content of crude
      protein in the consumed diet (198 +/- 3.09 g CP/kg DM and 208 +/- 8.57 g CP/kg
      DM, respectively). Due to C. jejuni infection, a significant increase in crude
      mucin in excreta at day 42 was seen in experimentally infected groups (62.6 +/-
      4.62 g/kg DM vs. 59.6 +/- 6.21 g/kg DM, respectively; p = 0.0396). There were
      significantly deeper crypts in infected birds (256 +/- 71.6 vs. 234 +/- 61.3
      MUm). In summary, C. jejuni infections significantly alter the feed intake
      behavior of broiler chickens regarding higher protein intake. Therefore, targeted
      manipulation of protein supply could be tested for limiting the spread of
      infection.

PMID- 30234122
TI  - Ectopic Fat Accumulation in Distinct Insulin Resistant Phenotypes; Targets for
      Personalized Nutritional Interventions.
AB  - Cardiometabolic diseases are one of the leading causes for disability and
      mortality in the Western world. The prevalence of these chronic diseases is
      expected to rise even further in the next decades. Insulin resistance (IR) and
      related metabolic disturbances are linked to ectopic fat deposition, which is the
      storage of excess lipids in metabolic organs such as liver and muscle. Notably, a
      vicious circle exists between IR and ectopic fat, together increasing the risk
      for the development of cardiometabolic diseases. Nutrition is a key-determining
      factor for both IR and ectopic fat deposition. The macronutrient composition of
      the diet may impact metabolic processes related to ectopic fat accumulation and
      IR. Interestingly, however, the metabolic phenotype of an individual may
      determine the response to a certain diet. Therefore, population-based nutritional
      interventions may not always lead to the most optimal (cardiometabolic) outcomes
      at the individual level, and differences in the metabolic phenotype may underlie
      conflicting findings related to IR and ectopic fat in dietary intervention
      studies. Detailed metabolic phenotyping will help to better understand the
      complex relationship between diet and metabolic regulation, and to optimize
      intervention outcomes. A subgroup-based approach that integrates, among others,
      tissue-specific IR, cardiometabolic parameters, anthropometrics, gut microbiota,
      age, sex, ethnicity, and psychological factors may thereby increase the efficacy
      of dietary interventions. Nevertheless, the implementation of more personalized
      nutrition may be complex, costly, and time consuming. Future studies are urgently
      warranted to obtain insight into a more personalized approach to nutritional
      interventions, taking into account the metabolic phenotype to ultimately improve
      insulin sensitivity and reduce the risk for cardiometabolic diseases.

PMID- 30234125
TI  - Robotic Approach to Ureteral Endometriosis: Surgical Features and Perioperative
      Outcomes.
AB  - Introduction: Surgical treatment of ureteral endometriosis is necessary to
      relieve urinary symptoms of obstruction and to preserve renal function. Which
      surgical approach to ureteral endometriosis should be considered the most
      appropriate is debated, due to the lack of scientific evidence. The aim of the
      present study is to assess the feasibility and to describe the perioperative
      outcomes of minimally invasive treatment of deep ureteral endometriosis using
      robotic assistance, highlighting the technical benefits and the limits of this
      approach. Method: A case-series including 31 consecutive patients affected by
      high-stage endometriosis including ureteral endometriosis using robotic
      assistance in our Department between November 2011 and September 2017. Results:
      All procedures were successfully completed by robotic technique, resulting in
      full excision of the parametrial nodules involving the ureter. Mean operating
      time was 184.8 +/- 81 min. Mean hospital stay was 4.02 +/- 3 days. Perioperative
      complications occurred in five patients and 4 out of 5 involved the urinary
      tract. Conclusions: Robotic surgery for deep infiltrating endometriosis of the
      ureter was feasible and allowed complete resection of ureteral nodules in all
      cases. No intraoperative complications arose, but a non-negligible rate of
      urinary tract complications was detected. This calls for a careful assessment of
      the benefits and specific risks associated with the use of robotic surgery for
      the treatment of deep infiltrating endometriosis of the ureter.

PMID- 30234126
TI  - Meckel's Diverticulum in Adults: Surgical Concerns.
AB  - Since Meckel's diverticulum (MD) is rarely diagnosed in adults, there is no
      consensus on what type of procedure to be performed for symptomatic MD and
      whether to resect or not an accidentally discovered MD. Treatment of symptomatic
      MD is definitive surgery, including diverticulectomy, wedge, and segmental
      resection. The type of procedure depends on: (a) the integrity of diverticulum
      base and adjacent ileum; (b) the presence and location of ectopic tissue within
      MD. The presence of ectopic tissue cannot be accurately predicted
      intraoperatively by palpation and macroscopic appearance. When present, its
      location can be predicted based on height-to-diameter ratio. Long diverticula
      (height-to-diameter ratio >2) have ectopic tissue located at the body and tip,
      whereas short diverticula have wide distribution of ectopic tissue including the
      base. When indication of surgery is simple diverticulitis, diverticulectomy
      should be performed for long and wedge resection for short MD. When indication of
      surgery is complicated diverticulitis with perforated base, complicated
      intestinal obstruction and tumor, wedge, or segmental resection should be
      performed. When the indication of surgery is bleeding, wedge and segmental
      resection are the preferred methods for resection. Regarding management of
      incidentally discovered MD, routine resection is not indicated. The decision
      making should be based on risk factors for developing future complications, such
      as: (1) patient age younger than 50 years; (2) male sex; (3) diverticulum length
      >2 cm; and (4) ectopic or abnormal features within a diverticulum. In this case,
      diverticulectomy should be performed for long and wedge resection for short MD.

PMID- 30234127
TI  - Protocols for Subtomogram Averaging of Membrane Proteins in the Dynamo Software
      Package.
AB  - Cryo-electron tomography allows low-resolution three-dimensional (3D) viewing of
      cellular organelles and macromolecular complexes present as multiple copies
      within a tomogram. These structures are computationally extracted and averaged in
      order to obtain high-resolution 3D structures, and provide a map of their spatial
      distribution and interaction with their biological microenvironment. To do so, we
      apply the user-friendly Dynamo software package on a tomographic data set. Dynamo
      acts as a modular toolbox adaptable to different biological scenarios, allowing a
      custom designed pipeline for subtomogram averaging. Here, we use as a textbook
      example the mitochondrial docking site of the positive-strand RNA Flock house
      nodavirus (FHV) to describe how Dynamo coordinates several basic steps in the
      subtomogram averaging workflow. Our framework covers specific strategies to deal
      with additional issues in subtomogram averaging as tomographic data management,
      3D surface visualization, automatic assignment of asymmetry and inherent loss of
      Fourier information in presence of preferential views.

PMID- 30234124
TI  - A Comparative Review on Microbiota Manipulation: Lessons From Fish, Plants,
      Livestock, and Human Research.
AB  - During recent years the impact of microbial communities on the health of their
      host (being plants, fish, and terrestrial animals including humans) has received
      increasing attention. The microbiota provides the host with nutrients, induces
      host immune development and metabolism, and protects the host against invading
      pathogens (1-6). Through millions of years of co-evolution bacteria and hosts
      have developed intimate relationships. Microbial colonization shapes the host
      immune system that in turn can shape the microbial composition (7-9). However,
      with the large scale use of antibiotics in agriculture and human medicine over
      the last decades an increase of diseases associated with so-called dysbiosis has
      emerged. Dysbiosis refers to either a disturbed microbial composition (outgrowth
      of possible pathogenic species) or a disturbed interaction between bacteria and
      the host (10). Instead of using more antibiotics to treat dysbiosis there is a
      need to develop alternative strategies to combat disturbed microbial control. To
      this end, we can learn from nature itself. For example, the plant root (or
      "rhizosphere") microbiome of sugar beet contains several bacterial species that
      suppress the fungal root pathogen Rhizoctonia solani, an economically important
      fungal pathogen of this crop (11). Likewise, commensal bacteria present on
      healthy human skin produce antimicrobial molecules that selectively kill skin
      pathogen Staphylococcus aureus. Interestingly, patients with atopic dermatitis
      (inflammation of the skin) lacked antimicrobial peptide secreting commensal skin
      bacteria (12). In this review, we will give an overview of microbial manipulation
      in fish, plants, and terrestrial animals including humans to uncover conserved
      mechanisms and learn how we might restore microbial balance increasing the
      resilience of the host species.

PMID- 30234128
TI  - Quantification of Intrinsically Disordered Proteins: A Problem Not Fully
      Appreciated.
AB  - Protein quantification is essential in a great variety of biochemical assays, yet
      the inherent systematic errors associated with the concentration determination of
      intrinsically disordered proteins (IDPs) using classical methods are hardly
      appreciated. Routinely used assays for protein quantification, such as the
      Bradford assay or ultraviolet absorbance at 280 nm, usually seriously misestimate
      the concentrations of IDPs due to their distinct and variable amino acid
      composition. Therefore, dependable method(s) have to be worked out/adopted for
      this task. By comparison to elemental analysis as the gold standard, we show
      through the example of four globular proteins and nine IDPs that the ninhydrin
      assay and the commercial QubitTM Protein Assay provide reliable data on IDP
      quantity. However, as IDPs can show extreme variation in amino acid composition
      and physical features not necessarily covered by our examples, even these
      techniques should only be used for IDPs following standardization. The far
      reaching implications of these simple observations are demonstrated through two
      examples: (i) circular dichroism spectrum deconvolution, and (ii) receptor-ligand
      affinity determination. These actual comparative examples illustrate the
      potential errors that can be incorporated into the biophysical parameters of
      IDPs, due to systematic misestimation of their concentration. This leads to
      inaccurate description of IDP functions.

PMID- 30234129
TI  - Surgical Techniques for Tricuspid Valve Disease.
AB  - Tricuspid valve disease affects millions of patients worldwide. It has always
      been considered less relevant than the left-side valves of the heart, but this
      "forgotten valve" still represents a great challenge for the cardiac surgeons,
      especially in the most difficult symptomatic scenarios. In this review we analyze
      the wide spectrum of surgical techniques for the treatment of a diseased
      tricuspid valve.

PMID- 30234130
TI  - Prolonged Postoperative Vasoplegia in Pediatric Patients on Chronic Angiotensin
      II Blocker Treatment.
AB  - Prolonged postoperative vasoplegia is known to occur following cardiac surgery in
      patients on chronic angiotensin II receptor blocker (ARB) treatment in adults.
      The perioperative management of these drugs in the pediatric population is not
      well described and here we would like to highlight this fact. While ARBs are
      increasingly used in children and adolescents with hypertension, there is lack of
      data to guide optimal pre-surgical management in the pediatric age group. We
      report two cases of prolonged vasoplegia following cardiopulmonary bypass
      occurring in adolescent patients on chronic ARB therapy and the importance of
      cessation of these drugs preoperatively.

PMID- 30234131
TI  - Decision Support for Mitigation of Livestock Disease: Rinderpest as a Case Study.
AB  - A versatile, interactive model to predict geographically resolved epidemic
      progression after pathogen introduction into a population is presented.
      Deterministic simulations incorporating a compartmental disease model run
      rapidly, facilitating the analysis of mitigations such as vaccination and
      transmission reduction on epidemic spread and progression. We demonstrate the
      simulation model using rinderpest infection of cattle, a devastating livestock
      disease. Rinderpest has been extinguished in the wild, but it is still a threat
      due to stored virus in some laboratories. Comparison of simulations to historical
      outbreaks provides some validation of the model. Simulations of potential
      outbreaks demonstrate potential consequences of rinderpest virus release for a
      variety of possible disease parameters and mitigations. Our results indicate that
      a rinderpest outbreak could result in severe social and economic consequences.

PMID- 30234132
TI  - Unconventional Vegetable Oils for a Reduction of Methanogenesis and Modulation of
      Ruminal Fermentation.
AB  - The objective of this study was to evaluate the use of vegetable oils from plants
      grown in Brazil, first using the in vitro batch culture, and then evaluating the
      oil with methane (CH4) reducing potential in an in vivo experiment. The in vitro
      experiment was conducted as a completely randomized design using the seven
      contrasting oils. Treatments consisted of a control and 3 increasing
      concentrations (0, 1, 2, and 5% v/v) of oil added to a tifton 85 hay samples. All
      vegetable oils linearly decreased (P < 0.01) gas production after 24 h of
      incubation, with the greatest reduction when 5% of oil was included into the
      diet. Acai and buriti had no effect of CH4 (% or mL/g DM incubated) however
      carrot, macauba, basil, passionflower, and pequi oil all linearly decreased (P <
      0.01) CH4 production with increasing inclusion rate of oil. Pequi oil resulted in
      the largest decrease in CH4 production (mL/g DM incubated) after 24 h of in vitro
      incubation. The objective of the in vivo experiment was to evaluate the effects
      of pequi oil on nutrient digestibility, CH4 production, and rumen fermentation
      parameters in wethers fed a hay-based diet. The experiment was conducted as a 2 *
      2 Latin Square design using 4 Dorper wethers (63.4 +/- 1.46 kg body weight).
      There were 2 experimental periods of 21 d each, with d 1-14 used for diet
      adaptation and d 15-21 for measurements and collections. The treatments consisted
      of a control diet and pequi oil fed at 70 g per animal per day. The addition of
      pequi oil to the diet had no effect on feed intake or the digestibility of
      nutrients, however there was a numerical decrease in the population of
      cellulolytic bacteria. There was a tendency (P = 0.06) for pequi oil addition to
      decrease CH4 production (g/d) by 17.5%. From this study, we can conclude that
      pequi oil may be used as a suitable oil for reducing CH4 production from
      ruminants, with no negative effects on intake or digestibility.

PMID- 30234133
TI  - The ASA Physical Status Classification: What Is the Evidence for Recommending Its
      Use in Veterinary Anesthesia?-A Systematic Review.
AB  - Background: The effectiveness of the American Society of Anesthesiologists (ASA)
      Physical Status (PS) classification to identify the animals at a greater risk of
      anesthesia-related death and complications is controversial. In this systematic
      review, we aimed to analyze studies associating the ASA PS scores with the
      outcome of anesthesia and to verify whether there was any evidence for
      recommending the use of the ASA PS in veterinary patients. Methods: Research
      articles found through a systematic literature search were assessed for
      eligibility, and data were extracted and analyzed using random-effects analysis.
      Results: A total of 15 observational prospective and retrospective studies
      including 258,298 dogs, cats, rabbits, and pigs were included. The analysis found
      consistency between the studies showing that dogs, cats and rabbits with an ASA
      PS >=III had 3.26 times (95% CI = 3.04-3.49), 4.83 times (95% CI = 3.10-7.53),
      and 11.31 times (95% CI = 2.70-47.39), respectively, the risk of anesthesia
      related death within 24 h (dogs) and 72 h (cats and rabbits) after anesthesia
      compared with those with an ASA PS <III. In addition, the analysis showed that
      dogs and cats with ASA PS >=III had 2.34 times the risk of developing severe
      hypothermia during anesthesia (95% CI = 1.82-3.01). Conclusions: The simple and
      practical ASA PS was shown to be a valuable prognostic tool and can be
      recommended to identify an increased risk of anesthetic mortality until 24-72 h
      after anesthesia, and a greater risk of development severe intraoperative
      hypothermia.

PMID- 30234134
TI  - Induction of Synovitis Using Interleukin-1 Beta: Are There Differences in the
      Response of Middle Carpal Joint Compared to the Tibiotarsal Joint?
AB  - Background: The effects of recombinant interleukin-1beta (rIL-1beta) have been
      described for the middle carpal joint (MCJ). However, we are unaware of any
      studies that have described the cytological response of the tibiotarsal joint
      (TTJ) to rIL-1beta or compared the clinical and cytological responses of the MCJ
      to the TTJ following the administration of intra-articular rIL-1beta. Such
      information is critical for researchers planning to use rIL-1beta to create acute
      synovitis models in horses. Objectives: To compare the clinical and cytological
      responses of the MCJ to the TTJ following administration of intra-articular rIL
      1beta. Methods: Twelve horses were used for the study. Eight horses received 75
      ng of rIL-1beta into the MCJ and four horses received 75 ng of rIL-1beta into the
      TTJ. Clinical and cytological outcome parameters including lameness, joint
      circumference, joint effusion score, total nucleated cell count, cellular
      differentials, C-reactive protein, and prostaglandin-E2 concentrations were
      determined at baseline and multiple post-treatment time points over a 336 h
      period (2 weeks). Results: Recombinant IL-1beta administered into the TTJ
      resulted in a significantly greater respiratory rate at 24 h and heart rate at 12
      h when compared to rIL-1beta administered into the MCJ. In addition, the TTJ had
      a significantly greater increase in joint circumference at 24 post-injection hour
      (PIH) and subjective effusion grade at 24 PIH and 336 PIH. The MCJ had
      significantly higher total protein concentration at 6 PIH, and a significantly
      higher NCC at 24 and 72 PIH when compared to the TTJ. Conversely, the TTJ had
      significantly higher neutrophilic infiltration than the MCJ at 6 PIH and 168 PIH.
      Conclusions: This study establishes that the same intra-articular dose of rIL-1
      beta elicits significantly different clinical and cytological responses in the
      MCJ compared to the TTJ in the equine model of intra-articular synovitis. In
      addition, clinical and cytological evidence of synovitis may persist up to or >1
      week following intra-articular administration of rIL-1 beta.

PMID- 30234135
TI  - Clinical Findings in Dogs Trained for Awake-MRI.
AB  - Training dogs for awake-MRI began in 2012 for the study of canine cognition.
      Although originally envisioned as a research technique to understand the neural
      mechanisms of canine cognitive function, its potential as a new diagnostic
      clinical tool has become apparent. A high-quality structural scan of the brain
      can be acquired without sedation or anesthesia in as little as 30 s in a well
      trained dog. This has opened the possibility of longitudinal imaging of CNS
      disease with MRI both as a means of monitoring treatment and potentially as a
      surveillance tool for inflammatory and neoplastic brain diseases in high-risk
      breeds. This same training can be used to image other body regions, such as the
      abdomen, enabling clinicians to screen for abdominal disease using cross
      sectional imaging without the need for anesthesia and without exposing the
      patient to ionizing radiation. We present four examples of dogs trained for awake
      MRI who developed: (1) nasal carcinoma; (2) brain tumor; (3) abdominal lipoma;
      (4) idiopathic epilepsy.

PMID- 30234136
TI  - Pilot Study to Evaluate the Association Between the Length of the Luteal Phase
      and Estrous Activity Detected by Automated Activity Monitoring in Dairy Cows.
AB  - The ability of automated activity monitoring (AAM) systems to detect estrus is
      influenced by multiple variables. The luteal phase (LP) preceding estrus has been
      shown to be important for hormones release, and behavior during estrus in
      ruminants, but its impact on activity as measured by AAM systems has not been
      studied. The objective of this study was to investigate the impact of the length
      of the preceding LP on the intensity and duration of estrus as measured by AAM,
      and on the expression of estrogen receptor alpha (ERalpha) in the endometrium. A
      total of 60 cows between 46 and 53 days in milk were assigned to either a normal
      or a short length LP. Length of the LP was insured by the use of hormonal
      synchronization programs. Cows in both treatments were matched on parity, milk
      production, body condition score (BCS), and lameness score (assessed at
      enrolment). Expression of ERalpha receptors in the endometrium were evaluated by
      nuclear staining by immunohistochemistry of biopsies. Estrus was defined as the
      day on which the AAM system detected estrus. Cows that were not synchronized by
      the protocol or that were not detected in estrus by the AAM systems were
      excluded, which left 21 and 11 cows for analyses in the normal and short length
      LP, respectively. Peak activity index of estrus, duration of estrus, and
      expression of ERalpha were outcomes for multivariable linear regression models.
      Cows with short length LP tended to have lower peak activity at estrus, but there
      was no significant effect of treatment when BCS was accounted for. Cows with BCS
      <= 2.5 had less intense and shorter estrus than cows with BCS >= 2.75. There was
      no association between the length of the LP and the expression of ERalpha in the
      endometrium.

PMID- 30234137
TI  - Assessment of Myocardial Perfusion at Rest and During Stress Using Dynamic First
      Pass Contrast-Enhanced Magnetic Resonance Imaging in Healthy Dogs.
AB  - Objective: To assess the feasibility of myocardial perfusion analysis in healthy
      dogs using dynamic contrast-enhanced cardiac magnetic resonance (DCE-MR) imaging
      at rest and during simulated stress with two doses of adenosine. Animals: Ten
      healthy beagle dogs. Procedures: Dogs were anesthetized and positioned in dorsal
      recumbency in a 3.0 Tesla MR scanner. Electrocardiogram-triggered dynamic T1
      weighted ultrafast gradient echo images of three slices in short-axis orientation
      of the heart were acquired during breath holds and the first pass of gadolinium
      contrast. Image acquisition was performed after 4 min infusion of 140 MUg/kg/min
      and 280 MUg/kg/min adenosine and, after a washout period, without adenosine,
      respectively. Images were processed by dividing each slice into 6 radial segments
      and perfusion analysis was performed from signal intensity-time data. Results: No
      differences in perfusion parameters were found between segments within any of the
      slices, but significant differences were found between slices for peak
      enhancement, accumulated enhancement, and the maximum upslope. In addition,
      significant differences were found within each slice between data at rest and
      during adenosine-induced stress for the relative and absolute maximum upslope,
      relative peak enhancement, time to peak, and accumulated enhancement although
      inter-individual variation was large and no difference was found between the two
      stress tests for some parameters. Conclusion and Clinical Relevance: Results of
      this study showed that rest and stress myocardial perfusion can be assessed using
      DCE-CMR in dogs using the methods described. Both, adenosine dose and slice
      appear to affect perfusion parameters in healthy dogs and individual response to
      adenosine was variable.

PMID- 30234139
TI  - Role of circulating tumor DNA to help decision-making in hepatocellular
      carcinoma.

PMID- 30234138
TI  - Assessing the Effects of Stocking Density on Turkey Tom Health and Welfare to 16
      Weeks of Age.
AB  - Four levels of turkey tom stocking density (SD) (30, 40, 50, 60 kg/m2) were
      evaluated in two 16 week trials (n = 2,868 Nicholas Select). Poults were
      allocated to one of eight independently ventilated rooms per trial (6.71 * 10.06
      m) based on final predicted body weight (two replicates per SD per trial). Room
      temperature, humidity, carbon dioxide and ammonia concentration were recorded
      throughout the trial; ventilation was adjusted to equalize air quality across
      treatments. Mobility (gait score, scale 0-5) was recorded at 12 and 16 weeks (20
      birds per replicate). Footpad lesion score (scale 0-4), feather condition (scale
      1-4), and cleanliness scores (scale 1-4) were recorded at 10 (Trial 2), 12, and
      16 weeks of age (20 birds per replicate). Aggressive injury incidence was
      recorded daily for Trial 2. Stress (heterophil/lymphocyte ratio) was evaluated at
      4, 12, and 16 weeks of age (15 birds per replicate). Behavior was recorded and
      scan sampled (field of view) at 12 (Trial 1), 14, and 16 weeks. Data were
      analyzed using regression analysis (linear, Proc Reg; quadratic, Proc RSReg) for
      relationships between the variables and SD. Differences were considered
      significant when p <= 0.05. Mobility and footpad lesions were negatively affected
      by increasing SD (linear) at 16 weeks only. Feather condition and cleanliness
      decreased linearly as SD increased at week 10, 12, and 16. The incidence of
      aggressive damage was higher as SD increased during week 4-8 (quadratic).
      Heterophil/lymphocyte ratios increased linearly at 4 weeks (similar trend at 12
      weeks). Behavior was impacted at 12 weeks of age with standing behavior showing a
      quadratic response, and walking and total disturbance showing a linear decrease
      as SD increased. Resting, preening, and comfort behaviors increased linearly (14
      weeks), while walking and strutting decreased linearly with increasing SD.
      Finally, at 16 weeks of age resting, standing, walking, feeding, and total
      disturbance responded quadratically while preening behavior increased linearly
      with increasing SD. Results suggest that increasing SD negatively impacts bird
      health and wellbeing through decreased mobility, increased footpad lesions,
      poorer feather condition and cleanliness, and behavioral changes, but that very
      low SD (30 kg/m2) may result in increased aggressive damage.

PMID- 30234140
TI  - Hemangioblast: origin of hemangioblastoma in von Hippel-Lindau (VHL) syndrome.

PMID- 30234141
TI  - Attenuation of YAP1 can potentially target cancer stem cells to overcome drug
      resistance.

PMID- 30234142
TI  - Proteomics of prostate cancer - revealing how cancer cells master their messy
      genomes.

PMID- 30234143
TI  - BCL-2 inhibition is a promising therapeutic strategy for small cell lung cancer.

PMID- 30234144
TI  - Docetaxel increases the risk of severe infections in the treatment of non-small
      cell lung cancer: a meta-analysis.
AB  - The purpose of this study was to determine whether docetaxel increases the risk
      of severe infections in patients with non-small cell lung cancer. A thorough
      literature search of the PubMed, EMBASE and Cochrane Central Register of
      Controlled Trials databases was performed (up to February 28, 2017) without any
      language restrictions. In addition, we searched the www.clinicaltrials.gov
      website and checked each reference listed in the included studies, relevant
      reviews and guidelines. We also included randomized controlled trials that
      reported severe infections in patients with non-small cell lung cancer who were
      administered docetaxel. A meta- analysis was conducted using relative risk and
      random effects models in Stata 14.0 software. Sensitivity analysis and meta
      regression were performed using Stata 14.0 software. We identified 354 records
      from the initial search, and this systematic review ultimately included 43 trials
      with 12,447 participants. The results of our meta- analysis showed that docetaxel
      increased the risk of severe infections [relative risk: 2.10, 95% confidence
      interval: 1.51-2.93, I2 = 69.6%, P = 0.000]. Meta-regression analysis indicated
      that the type of intervention was a major source of heterogeneity. Our systematic
      review and meta-analysis suggest that docetaxel is associated with the risk of
      severe infections.

PMID- 30234145
TI  - A survey of current surgical treatment of early stage breast cancer in China.
AB  - The purpose of this national survey is to explore the patterns of surgical
      management for early stage breast cancer patients in China. A paper questionnaire
      survey was sent to the representatives from 520 hospitals who attended an
      international symposium in Guangzhou, China, 2014. The questionnaire included
      demographic information, initials and most preferred approaches for breast cancer
      surgery. The results were presented descriptively. The response rate was 42.5%.
      Only 7% of hospitals with >50% rate of breast conserving surgery (BCS).
      Intraoperative frozen sections and additional cavity margins assessment were used
      at 88% and 30.9% of hospitals, respectively. For invasive carcinoma, 15% of
      participants defined an adequate margin as no tumor cells on the ink. Sentinel
      lymph node biopsy (SLNB) was routinely performed in 93.2% of hospitals. Only
      16.6% of hospitals would embrace the conclusions of the American College of
      Surgeons Oncology Group (ACOSOG) Z0011 study and omit axillary lymph node
      dissection (ALND) for patients who fit the Z0011 criteria. The current patterns
      for the management of breast cancer patients are still lagging behind. Chinese
      doctors need to catch up with the updated results of the cutting-edge clinical
      studies and multiple measures are in need to improve this situation.

PMID- 30234146
TI  - Biological role of miR-204 and miR-211 in melanoma.
AB  - In this short report, we pinpoint some technical and conceptual flaws that we
      found in the article entitled "miR-204-5p and miR-211-5p contribute to BRAF
      inhibitor resistance in melanoma" (Diaz-Martinez et al., Cancer Research 2018).
      We also discuss how, in our opinion, these flaws led Diaz-Martinez and colleagues
      to incorrect conclusions about the biological role that miR-204 and miR-211 play
      in melanoma and about the terms of their involvement in the phenomenon of
      resistance to BRAF inhibitors.

PMID- 30234147
TI  - Assessment of cytotoxicity of leaf extracts of Andrographis paniculata and
      Aspilia africana on murine cells in vitro.
AB  - People, especially in rural environments and recently, those dissatisfied with
      conventional medicine use medicinal plants for their therapeutic effects. Two or
      more plants are usually combined for such use and these combinations cause
      interactions that may be safe but could also be detrimental to health. Used
      singly, Andrographis paniculata and Aspilia africana are considered safe plants
      with low toxicities but little is known about their safety in combined therapy.
      This study assessed the cytotoxic activities of the aqueous, methanol and
      chloroform extracts of the two plants in a 1:1 combination at various
      concentrations on murine hepatocytes, thymocytes and splenocytes. The murine
      cells were seeded in microtitre plates and tested with the combined extracts at
      different concentrations and percentage viability values of the cells determined
      by the tetrazolium salt reduction assay (MTT). The extracts used were: combined
      aqueous extract of the two plants (CAE), and combined chloroform extract (CCE).
      At 72hr incubation with 500 MUg/ml extract concentration, percentage viability
      was low. Splenocytes thymocytes and hepatocytes incubated with CAE had viability
      values of 35%, 28% and 64% respectively and with CCE, 26%, 26% and 36%
      respectively, relative to controls. From the results, the extracts were cytotoxic
      to the murine cells at this concentration and incubation period. These low values
      indicate cytotoxic interactions in the combined extracts. However more research
      is needed to understand the mechanisms of cytotoxicity of the plants.

PMID- 30234148
TI  - Donor-derived Cell-free DNA Identifies Antibody-mediated Rejection in Donor
      Specific Antibody Positive Kidney Transplant Recipients.
AB  - Background: Elevated levels of donor-derived cell-free DNA (dd-cfDNA) in the
      plasma of renal allograft recipients indicates organ injury and an increased
      probability of active rejection. Donor-specific antibodies (DSA) to HLA antigens
      are associated with risk of antibody-mediated rejection (ABMR). This study
      assessed the combined use of dd-cfDNA and DSA testing to diagnose active ABMR.
      Methods: Donor-derived cell-free DNA was assayed in 90 blood samples with paired
      DSA and clinically indicated biopsies from 87 kidney transplant patients. Sixteen
      cases met criteria for active ABMR. Performance characteristics of dd-cfDNA for
      diagnosis of active ABMR were determined for samples with prior or current
      positive DSA (DSA+, n = 33). Results: The median level of dd-cfDNA (2.9%) in DSA+
      patients with active ABMR was significantly higher than the median level (0.34%)
      in DSA+ patients without ABMR (P < 0.001). The median level of dd-cfDNA in DSA-
      patients was 0.29%. The positive predictive value of dd-cfDNA (at 1%) to detect
      active ABMR in DSA+ patients was 81%, whereas the negative predictive value was
      83%. The positive predictive value for DSA+ alone was 48%. Conclusions: The
      combined use of dd-cfDNA and DSA testing may improve the noninvasive diagnosis of
      active ABMR in kidney transplant patients. Patients with dd-cfDNA+/ DSA+ results
      have a high probability of active ABMR.

PMID- 30234149
TI  - Efficacy and Safety of a Tofacitinib-based Immunosuppressive Regimen After Kidney
      Transplantation: Results From a Long-term Extension Trial.
AB  - Background: Tofacitinib is an oral Janus kinase inhibitor. This open-label, long
      term extension (LTE) study (NCT00658359) evaluated long-term tofacitinib
      treatment in stable kidney transplant recipients (n = 178) posttransplant.
      Methods: Patients who completed 12 months of cyclosporine (CsA) or tofacitinib
      treatment in the phase IIb parent study (NCT00483756) were enrolled into this LTE
      study, evaluating long-term tofacitinib treatment over months 12 to 72
      posttransplant. Patients were analyzed by tofacitinib less-intensive (LI) or more
      intensive (MI) regimens received in the parent study. For both groups,
      tofacitinib dose was reduced from 10 to 5 mg twice daily by 6 months into the
      LTE. Patients were followed up through month 72 posttransplant, with a focus on
      month 36 results. Results: Tofacitinib demonstrated similar 36-month patient and
      graft survival rates to CsA. Biopsy-proven acute rejection rates at month 36 were
      11.2% for CsA, versus 10.0% and 7.4% (both P > 0.05) for tofacitinib LI and MI,
      respectively. Least squares mean estimated glomerular filtration rates were 9 to
      15 mL/min per 1.73 m2 higher for tofacitinib versus CsA at month 36. The
      proportions of patients with grade 2/3 interstitial fibrosis and tubular atrophy
      in month 36 protocol biopsies were 20.0% for LI and 18.2% for MI (both P > 0.05)
      versus 33.3% for CsA. Kaplan-Meier cumulative serious infection rates at month 36
      were numerically higher for tofacitinib LI (43.9%; P = 0.45) and significantly
      higher for MI (55.9%; P < 0.05) versus CsA (37.1%). Conclusions: Long-term
      tofacitinib continued to be effective in preventing renal allograft acute
      rejection and preserving renal function. However, long-term tofacitinib and
      mycophenolic acid product combination was associated with persistent serious
      infection risk.

PMID- 30234150
TI  - Impact of Deceased Donor Cardiac Arrest Time on Postpancreas Transplant Graft
      Function and Survival.
AB  - Introduction: Transplantation of pancreas allografts from donors that have
      experienced preprocurement cardiopulmonary arrest (PPCA) is not common, though
      use of PPCA grafts is routine in liver and kidney transplantation. This article
      reviews a large number of PPCA pancreas grafts at a single center and reports
      posttransplant outcomes including early graft dysfunction, length of hospital
      stay, rejection, and early and late graft survival. Methods: Preprocurement
      cardiopulmonary arrest, arrest time, and donor and recipient pancreatic enzyme
      levels were collected from electronic and written medical records. The PPCA
      donors were stratified into 4 groups: none, less than 20 minutes, 20-39 minutes,
      and 40 minutes or greater. Graft survival was assessed at 7 and 90 days and at 1
      year. Long-term graft survival was assessed by Cox regression analysis. Results:
      The records of 606 pancreas transplants were reviewed, including 328 (54%)
      simultaneous pancreas and kidney transplants. Preprocurement cardiopulmonary
      arrest occurred in 176 donors (29%; median time, 20 minutes). Median peak donor
      lipase was higher in PPCA donors (40 MU/L vs 29 MU/L, P = 0.02). Posttransplant,
      peak recipient amylase, and lipase levels were similar (P = 0.63). Prolonged
      arrest time (>40 minutes) was associated with higher donor peak lipase and lower
      recipient peak amylase (P = 0.05 for both). Stratified by donor arrest time,
      there was no difference in 7-day, 90-day, or 1-year graft survival. Cox
      regression comparing the 4 groups demonstrated no statistical difference in 10
      year survival. Conclusions: These results support transplantation of pancreas
      allografts from PPCA donors. Prolonged asystole was associated with higher peak
      donor serum lipase but lower peak recipient serum amylase. There were no
      differences in allograft survival.

PMID- 30234151
TI  - Identification and Validation of the Predictive Capacity of Risk Factors and
      Models in Liver Transplantation Over Time.
AB  - Background: Outcome after liver transplantation (LT) is determined by donor,
      transplant and recipient risk factors. These factors may have different impact on
      either patient or graft survival (outcome type). In the literature, there is wide
      variation in the use of outcome types and points in time (short term or long
      term). Objective of this study is to analyze the predictive capacity of risk
      factors and risk models in LT and how they vary over time and per outcome type.
      Methods: All LTs performed in the Netherlands from January 1, 2002, to December
      31, 2011, were analyzed with multivariate analyses at 3-month, 1-year, and 5-year
      for patient and (non-)death-censored graft survival. The predictive capacity of
      the investigated risk models was compared with concordance indices. Results:
      Recipient age, model for end-stage liver disease sodium, ventilatory support,
      diabetes mellitus, hepatocellular carcinoma, previous malignancy, hepatitis C
      virus antibody, hepatitis B virus antibody, perfusion fluid, and Eurotransplant
      donor risk index (ET-DRI) had significant impact on outcome (graft or patient
      survival) at 1 or multiple points in time. Significant factors at 3-month patient
      survival (recipient age, model for end-stage liver disease sodium, ventilatory
      support) were used to compose a concept model. This model, had a higher c-index
      than the balance-of-risk score, DRI, ET-DRI, donor-recipient model and simplified
      recipient risk index for long-term patient and non-death-censored graft survival.
      Conclusions: In this study, the effects of recipient risk factors and models on
      different outcome types and time points were shown. Short-term patient survival
      mainly depends on recipient risk factors, long-term graft survival on donor risk
      factors and is more difficult to predict. Next to the concept model, the donor
      recipient model has a higher predictive capacity to other risk models for (long
      term) patient and non-death-censored graft survival. The DRI and ET-DRI best
      predicted death-censored graft survival. Knowledge about risk factors and models
      is critical when using these for waitlist management and/or help in organ
      allocation and decision-making.

PMID- 30234152
TI  - Perspectives on Quality of Care in Kidney Transplantation: A Semistructured
      Interview Study.
AB  - Background: There is currently no agreement as to what constitutes quality
      transplant care, and there is a lack of consistency in the approach to assessing
      transplantation quality. We aimed to ascertain the views of patients, clinicians,
      and program administrators about quality care for kidney transplant patients.
      Methods: Semistructured qualitative interviews were conducted with 20 patients,
      17 physicians, and 11 program administrators. Transcripts were analyzed using
      inductive thematic analysis. Results: We identified 8 themes: access to treatment
      (standardized transplant referral, lengthy transplant evaluation process, lengthy
      living donor evaluation); accessibility of services (alternative access options,
      flexible appointment availability, appropriate amount of follow-up, barriers for
      accessing care); program resources (comprehensive multidisciplinary care,
      knowledgeable staff, peer support groups, educational resources, patient
      navigators/ advocates); communication of information (taking time to answer
      questions, clear communication about treatment, communication tailored to
      patients, health promotion and illness prevention); attitude of care providers
      (positive and supportive attitude, patient centered care); health outcomes
      (freedom from dialysis, Long-term health, short-term health, fear of infections);
      patient satisfaction (returning to normal life, patient satisfaction with care);
      and safety (reducing infection risk, quick response to complications, patient
      health status on the waitlist). Conclusions: There is a need to move beyond basic
      clinical outcomes and focus on increasing ease of access, the patient-provider
      relationship, and outcomes that are most important to the patients.

PMID- 30234153
TI  - Antithrombin Perfluorocarbon Nanoparticles Improve Renal Allograft Function in a
      Murine Deceased Criteria Donor Model.
AB  - Background: Over 100 000 patients await renal transplantation and 4000 die per
      year. Compounding this mismatch between supply and demand is delayed graft
      function which contributes to short-term and long-term graft failures.
      Previously, we reported that thrombin-targeted perfluorocarbon nanoparticles (PFC
      NP) protect kidneys from ischemic renal injury after transient arterial
      occlusion. Here we hypothesize that perfusion of renal allografts with PFC-NP
      similarly can protect graft function after an ischemic interval. Methods: After
      60 minutes of warm ischemia, male Lewis rats underwent left renal explantation
      followed by renal perfusion with 5 mL of standard perfusate alone (N = 3) or with
      0.3 mL of untargeted PFC-NP (N = 5) or 0.3 mL thrombin-targeted of PFC NP
      functionalized with phenylalanine-proline-arginine-chloromethylketone (PPACK)
      (PFC-PPACK), an irreversible thrombin inhibitor (N = 5). Kidneys underwent 6
      hours of cold storage, followed by transplantation into recipients and native
      nephrectomy. Animals were euthanized at 24 hours for tissue collection or at 48
      hours for blood and renal tissue collection. A survival experiment was performed
      using the same protocol with saline control (N = 3), PFC-NP (N = 3) or PFC-PPACK
      (N = 6). Results: Serum creatinine was improved for the PFC-PPACK groups as
      compared with control groups (P < 0.04). Kaplan-Meier survival curves also
      indicated increased longevity (P < 0.05). Blinded histologic scoring revealed
      markedly attenuated renal damage in the PFC-PPACK group compared to untreated
      animals (2.75 +/- 1.60 versus 0.83 +/- 3.89; P = 0.0001) and greater preservation
      of renal vasculature. Conclusions: These results validate an NP-based approach to
      improve renal graft function as antithrombin NPs improved allograft function,
      decreased renal damage, protected vasculature, and improved longevity.

PMID- 30234154
TI  - Anti-HLA Donor-Specific IgG Subclasses and C1q-binding Evolution in
      Posttransplant Monitoring.
AB  - Background: The identification of low-level antibodies by single-antigen bead
      methodology has brought advancements to risk evaluation of kidney transplant
      recipients. However, the use of mean fluorescence intensity (MFI) to quantify
      antibodies and to guide therapy is not enough. Notably, immunoglobulin G (IgG)
      subclass switching is hypothesized to follow a programmed sequence after an
      emergency signal from the germinal center. In transplantation this process is not
      clear yet. In the present study, we sequentially evaluate anti-HLA donor specific
      antibody (DSA) subclasses, their profile changes, and C1q-binding ability and the
      influence of those characteristics on antibody mediated rejection (AMR)
      occurrence and allograft function. Methods: A total of 30 DSA-positive patients
      were tested for IgG subclass content and C1q-binding in sequential serum samples.
      Results: Twenty-one patients were DSA-positive before transplant; patients
      sensitized only by transfusion or pregnancies had IgG1 and/or IgG3, and patients
      sensitized by both transfusion and pregnancies or previous transplant showed a
      broader range of IgG subclasses. C1q binding was detected in high MFI made up of
      IgG1 or multiple IgG subclasses. Only 4 patients were positive for C1q
      posttransplantation and 3 of these showed an increase in MFI, changes in
      subclasses patterns, AMR, and allograft dysfunction. Conclusions: Posttransplant
      evaluation of DSA subclasses and the ability to bind C1q may be informative for
      both AMR occurrence and allograft dysfunction. Monitoring these events may help
      to better define risk and interventional time points.

PMID- 30234155
TI  - Unusual Bilateral Renal Parenchymal Urine Leak After Pediatric En Bloc Kidney
      Transplantation: First Case Study Report.
AB  - Kidney transplantation is usually the best course of treatment for patients with
      end-stage renal disease. En bloc kidney transplantation (EBKT) is a surgical
      treatment option that increases available donor organs with excellent graft
      survival for patients with end-stage renal disease. Herein, we report a case of
      an unusual bilateral renal parenchymal urine leak after EBKT leading to removal
      of both moieties of the EBKT. This unfortunate complication after EBKT, to our
      knowledge, is the only reported of its kind. We explore the possible causes of
      the bilateral parenchymal urine leaks and suggest preventive strategies to avoid
      urological complications after EBKT.

PMID- 30234157
TI  - Ergodic Exploration Using Binary Sensing for Nonparametric Shape Estimation.
AB  - Current methods to estimate object shape-using either vision or touch-generally
      depend on high-resolution sensing. Here, we exploit ergodic exploration to
      demonstrate successful shape estimation when using a low-resolution binary
      contact sensor. The measurement model is posed as a collision-based tactile
      measurement, and classification methods are used to discriminate between shape
      boundary regions in the search space. Posterior likelihood estimates of the
      measurement model help the system actively seek out regions where the binary
      sensor is most likely to return informative measurements. Results show successful
      shape estimation of various objects as well as the ability to identify multiple
      objects in an environment. Interestingly, it is shown that ergodic exploration
      utilizes non-contact motion to gather significant information about shape. The
      algorithm is extended in three dimensions in simulation and we present two
      dimensional experimental results using the Rethink Baxter robot.

PMID- 30234156
TI  - Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization
      and Upregulate Transitional and Regulatory B Cells.
AB  - Background: We hypothesized that immunomodulatory properties of mesenchymal
      stromal cells (MSC) may be considered for desensitization. Methods: Autologous or
      allogeneic bone marrow derived MSC were infused via tail vein at 0.5 M (0.5 *
      106), 1 M, or 2 M cells/dose on days -2, 3, 6, 9, 12 (prevention) or 14, 17, 20,
      23, 26 (treatment) relative to transfusion in a Brown Norway to Lewis rat model
      (10 groups total, n = 6 per group). Results: At 4 weeks, pooled analyses
      demonstrated that autologous and allogeneic MSC were equally effective in
      reducing IgG1 and IgG2a de novo donor-specific antibody (dnDSA, P < 0.001). Dose
      response studies indicated that moderate-dose MSC (5 M total) was most effective
      in reducing IgG1, IgG2a, and IgG2c dnDSA (P <= 0.01). Time course studies
      determined that preventive and treatment strategies were equally effective in
      reducing IgG1 and IgG2a dnDSA (P <= 0.01). However, individual group analyses
      determined that moderate-dose (5 M) treatment with autologous MSC was most
      effective in reducing IgG1, IgG2a, and IgG2c dnDSA (P <= 0.01). In this group,
      dnDSA decreased after 1 week of treatment; regulatory B cells increased in the
      spleen and peripheral blood mononuclear cells; and transitional B cells increased
      in the spleen, peripheral blood mononuclear cells, and bone marrow (P < 0.05 for
      all). Conclusions: Our findings indicate that autologous MSC prevent transfusion
      elicited sensitization and upregulate transitional, and regulatory B cells.
      Additional studies are needed to determine the biological relevance of these
      changes after kidney transplantation.

PMID- 30234158
TI  - Exploring the Effects of U.S. Immigration Enforcement on the Well-being of
      Citizen-Children in Mexican Immigrant Families.
AB  - In this article, we draw on ecocultural theories of risk and resilience to
      examine qualitatively the experiences of U.S. citizen-children living with their
      undocumented Mexican parents. Of central importance is the fact that citizen
      children's daily lives are organized around the very real possibility that their
      undocumented parents could one day be detained and deported. Our purpose is to
      render visible the various ways in which citizen-children confront and navigate
      the possibilities-and realities-of parental deportation. We develop a framework
      to conceptualize the complex multidimensional, and often multidirectional,
      factors experienced by citizen-children vulnerable to or directly facing parental
      deportation. We situate youth well-being against a backdrop of multiple factors
      to understand how indirect and direct encounters with immigration enforcement,
      the mixed-status family niche, and access to resources shape differential child
      outcomes. In doing so, we offer insights into how different factors potentially
      contribute to resilience in the face of adversity.

PMID- 30234159
TI  - Port-Site Metastasis of Undiagnosed Pancreatic Adenocarcinoma After Laparoscopic
      Radical Prostatectomy: Case Report and Literature Review.
AB  - Background: Laparoscopic port-site metastases remain rare for urologic tumors,
      despite the increasing use of laparoscopic techniques on the approach of urologic
      malignancy. Herein, we report a case of port-site mass after laparoscopic radical
      prostatectomy whose immunohistochemistry demonstrated metastasis from a
      pancreatic lesion. Case Presentation: A 62-year-old man presented to our
      ambulatory clinic with an elevated prostate-specific antigen (PSA) of 7.7 ng/mL.
      Transrectal biopsies revealed prostate cancer Gleason 6 (3 + 3) on the right
      side. He was subjected to a transperitoneal laparoscopic radical prostatectomy at
      our institution. The PSA on postoperative week 6 was 0.04 ng/mL. Three months
      after the surgery, he comes back to the emergency department complaining of an
      abdominal pain especially on the right flank. Our examination of the abdomen
      revealed a small palpable mass at the right upper port-site scar. Computed
      tomography of the abdomen and pelvis, with contrast, revealed a hypodense nodular
      lesion located on the abdominal wall near the upper port site and adjacent to the
      pancreatic tail. An excisional biopsy of the lesion confirmed the presence of
      metastatic adenocarcinoma. Immunohistochemistry demonstrated metastasis from a
      pancreatic lesion. Conclusion: Port-site mass after laparoscopic radical
      prostatectomy is uncommon especially in quite different tumors like this one with
      Gleason score 6 (3 + 3). Generally, port-site recurrences after a urologic
      laparoscopic surgery are uncommon and are not associated with diffused peritoneal
      carcinomatosis. Therefore, in this situation, another tumor site should be
      investigated as the primary source.

PMID- 30234160
TI  - Benefits of Computed Tomography in Reducing Mortality in Emergency Medicine.
AB  - Performing accurate diagnosis using computed tomography (CT) in emergency
      medicine may reduce mortality rates in various diseases. In this observational,
      correlational and cross-sectional study, we conducted multiple regression
      analyses to investigate the relationship between CT utilization rates and
      mortality. In addition, we estimated the annual net profits from CT to show the
      profitability of introducing a CT system in each Japanese prefecture. We
      conducted a multiple regression analysis to investigate correlations between CT
      utilization rates and mortality from each disease adjusted for the population
      density, number of doctors, as well as transportation time to the medical
      institution. The results of multiple regression analysis showed that traffic
      accident mortality was related to CT utilization rate and population density.
      Extrinsic death such as mortality due to falling, drowning and asphyxia was
      related to CT utilization, indicating that CT in emergency medicine reduced
      mortality. Moreover, the annual net profit from multi-slice CT (MSCT) was
      estimated as positive. Our study clearly demonstrates that CT utilization rates
      relate to a reduction in mortality from accidents, indicating that screening
      patients with CT in the emergency room has a beneficial effect and reduces
      mortality. Therefore, CT equipment has a beneficial effect in both emergency
      medicine and hospital management.

PMID- 30234161
TI  - Ipragliflozin Ameliorates Liver Damage in Non-alcoholic Fatty Liver Disease.
AB  - Background: There are few effective medications for non-alcoholic steatohepatitis
      (NASH). We investigated the efficacy of ipragliflozin (selective sodium-glucose
      cotransporter-2 inhibitor [SGLT2I]) for the treatment of patients with type 2
      diabetes mellitus (T2DM) complicated by non-alcoholic fatty liver disease
      (NAFLD). Methods: We prospectively enrolled patients with T2DM complicated by
      NAFLD treated at our institutions from January 2015 to December 2016. Patients
      received oral ipragliflozin (50 mg/day) once daily for 24 weeks. Body composition
      was evaluated using an InBody720 analyzer. We used transient elastography to
      measure liver stiffness and the controlled attenuation parameter for the
      quantification of liver steatosis in patients with NASH. Results: Forty-three
      patients with T2DM and NAFLD were enrolled (12 with biopsy-proven NASH and 31
      with NAFLD diagnosed by ultrasonography). After 24 weeks, body weight, hemoglobin
      A1c (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      gamma-glutamyl transpeptidase, body fat mass, and steatosis were significantly
      decreased compared to baseline measurements in patients with NASH. However,
      muscle mass was not reduced, and liver stiffness showed a statistically
      insignificant tendency to decrease. NAFLD patients also showed a significant
      reduction in body weight, HbA1c, AST, and ALT compared to baseline measurements.
      Conclusion: Ipragliflozin may be effective in patients with T2DM complicated by
      NAFLD.

PMID- 30234162
TI  - Midlife Self-Reported Social Support as a Buffer Against Premature Mortality
      Risks Associated with Childhood Abuse.

PMID- 30234163
TI  - Assessment of the intermediate care unit triage system.
AB  - Background: An important critique with respect to the utilization of intermediate
      care units (IMCU) is that they potentially admit patients who would otherwise be
      cared for on the regular ward. This would lead to an undesired waste of critical
      care resources. This article aims to (1) describe the caseload at the IMCU and
      (2) to assess the triage system at the IMCU to determine potentially unnecessary
      admissions. Methods: This cohort study included all admissions at the mixed
      surgical IMCU from 2001 to 2015. The Therapeutic Intervention Scoring System-28
      (TISS-28) was prospectively collected for all admissions to describe the caseload
      at the IMCU and to identify medical criteria for admission. These were combined
      with logistical criteria to assess the IMCU triage system. Results: A total of
      8816 admissions were included in the study. The average TISS-28 was 20.19 (95% CI
      18.05 to 22.33), corresponding with 3.57 (95% CI 3.19 to 3.94) hours of direct
      patient-related work per patient per nursing shift. Over time, this increased by
      an average of 0.27 points/year (p<0.001). Of all admissions, 6539 (74.2%) were
      medically considered to be justly admitted, and 7093 (80.4%) were logistically
      considered to be justly admitted. With these criteria combined, a total of 8324
      (94.4%) were correctly admitted. Discussion: Most admissions to the IMCU are
      medically and/or logistically necessary, as the majority of admitted patients
      demand a higher level of nursing care than available on the general ward.
      Continuous triage is thereby essential. These findings support further
      utilization of the IMCU in our current healthcare system and has important
      implications for IMCU-related management decisions. Level of evidence: Level VI.

PMID- 30234164
TI  - Morning report decreases length of stay in trauma patients.
AB  - Background: Modern acute care surgery (ACS) programs depend on consistent patient
      hand-offs to facilitate care, as most programs have transitioned to shift-based
      coverage. We sought to determine the impact of implementing a morning report (MR)
      model on patient outcomes in the trauma service of a tertiary care center.
      Methods: The University of Arkansas for Medical Sciences (UAMS) Division of ACS
      implemented MR in October 2015, which consists of the trauma day team, the
      emergency general surgery day team, and a combined night float team. This study
      queried the UAMS Trauma Registry and the Arkansas Clinical Data Repository for
      all patients meeting the National Trauma Data Bank inclusion criteria from
      January 1, 2011 to April 30, 2018. Bivariate frequency statistics and generalized
      linear model were run using STATA V.14.2. Results: A total of 11 253 patients
      (pre-MR, n=6556; post-MR, n=4697) were analyzed in this study. The generalized
      linear model indicates that implementation of MR resulted in a significant
      decrease in length of stay (LOS) in trauma patients. Discussion: This study
      describes an approach to improving patient outcomes in a trauma surgery service
      of a tertiary care center. The data show how an MR session can allow for patients
      to get out of the hospital faster; however, broader implications of these
      sessions have yet to be studied. Further work is needed to describe the decisions
      being made that allow for a decreased LOS, what dynamics exist between the
      attendings and the residents in these sessions, and if these sessions can show
      some of the same benefits in other surgical services. Level of evidence: Level 4,
      Care Management.

PMID- 30234165
TI  - Defining severe traumatic brain injury readmission rates and reasons in a rural
      state.
AB  - Background: Readmissions after a traumatic brain injury (TBI) have significant
      impact on long-term patient outcomes through interruption of rehabilitation. This
      study examined readmissions in a rural population, hypothesizing that readmitted
      patients after TBI will be older and have more comorbidities than those not
      readmitted. Methods: Discharge data on all patients 15 years and older who were
      admitted to an Arkansas-based hospital for TBI were obtained from the Arkansas
      Hospital Discharge Data System from 2010 to 2014. This data set includes
      diagnoses (principal discharge diagnosis, up to 3 external cause of injury codes,
      18 diagnosis codes using the International Classification of Disease, 9th
      Edition, Clinical Modifications), age, gender, and inpatient costs. Hospital Cost
      and Utilization Project Clinical Classification and Chronic Condition Indicator
      were used to identify chronic disease and body systems affected in principal
      diagnosis. Results: Of the 3114 cases of significant head trauma, more than two
      thirds were attributed to fall injuries, with motor vehicle crashes accounting
      for 20% of the remainder. The mean length of stay was 6.5 days. 691 of these
      patients were admitted to an Arkansas hospital in the following year, totaling
      1368 readmissions. Of the readmissions, 16.4% of patients were admitted for
      altered mental status, 12.9% with shortness of breath (SOB), and 9.4% with chest
      pain. Mental disorders (psychosis, dementia, and depression) and organic nervous
      symptoms (Alzheimer's disease, encephalopathy, and epilepsy) were the primary
      source of readmissions. More than one-third of the patients were admitted in the
      following year for chronic diseases such as heart failure (8.6%), psychosis
      (5.2%), and cerebral artery occlusion (4.1%). Discussion: This study showed that
      there is a significant rate of readmissions in the year after a diagnosis of TBI.
      Complications with existing chronic diseases are among the most reported reasons
      for admission in this time period, demonstrating the effect severe head trauma
      has on long-term treatment. Level of evidence: Level IV, Retrospective
      epidemiological study.

PMID- 30234166
TI  - Selective use of pericardial window and drainage as sole treatment for
      hemopericardium from penetrating chest trauma.
AB  - Background: Penetrating cardiac injuries (PCIs) are highly lethal, and a
      sternotomy is considered mandatory for suspected PCI. Recent literature suggests
      pericardial window (PCW) may be sufficient for superficial cardiac injuries to
      drain hemopericardium and assess for continued bleeding and instability. This
      study objective is to review patients with PCI managed with sternotomy and PCW
      and compare outcomes. Methods: All patients with penetrating chest trauma from
      2000 to 2016 requiring PCW or sternotomy were reviewed. Data were collected for
      patients who had PCW for hemopericardium managed with only pericardial drain, or
      underwent sternotomy for cardiac injuries grade 1-3 according to the American
      Association for the Surgery of Trauma (AAST) Cardiac Organ Injury Scale (OIS).
      The PCW+drain group was compared with the Sternotomy group using Fisher's exact
      and Wilcoxon rank-sum test with P<0.05 considered statistically significant.
      Results: Sternotomy was performed in 57 patients for suspected PCI, including 7
      with AAST OIS grade 1-3 injuries (Sternotomy group). Four patients had
      pericardial injuries, three had partial thickness cardiac injuries, two of which
      were suture-repaired. Average blood drained was 285 mL (100-500 mL). PCW was
      performed in 37 patients, and 21 had hemopericardium; 16 patients proceeded to
      sternotomy and 5 were treated with pericardial drainage (PCW+drain group). All
      PCW+drain patients had suction evacuation of hemopericardium, pericardial lavage,
      and verified bleeding cessation, followed by pericardial drain placement and
      admission to intensive care unit (ICU). Average blood drained was 240 mL (40-600
      mL), and pericardial drains were removed on postoperative day 3.6 (2-5). There
      was no significant difference in demographics, injury mechanism, Revised Trauma
      Score exploratory laparotomies, hospital or ICU length of stay, or ventilator
      days. No in-hospital mortality occurred in either group. Conclusions:
      Hemodynamically stable patients with penetrating chest trauma and hemopericardium
      may be safely managed with PCW, lavage and drainage with documented cessation of
      bleeding, and postoperative ICU monitoring. Level of evidence: Therapeutic study,
      level IV.

PMID- 30234167
TI  - Through-and-through gunshot wound to the esophagus at the thoracic inlet:a novel
      management approach.
AB  - : A 42-year-old man presented to the emergency department with gunshot wound to
      left upper back over the scapula and palpable bullet over the right
      supraclavicular fossa. The patient had a left-sided needle thoracostomy in the
      field. He was tachypneic and tachycardiac but normortensive on arrival. Due to
      the patient being in respiratory distress, he was orotracheally intubated. On
      examination, he was found to have a moderate left pneumothorax with mild
      mediastinal shift. He had a left closed tube thoracostomy placed. CT angiography
      imaging of the neck and chest was then obtained, and pneumomediastinum associated
      with bony fragmentation of the anterior T1 and T2 vertebral bodies was observed.
      Additional findings included right internal jugular injury and right apical
      pulmonary hemorrhage. The patient subsequently underwent flexible
      tracheobronchoscopy and esophagoscopy in the endoscopy suite, where a through-and
      through esophageal injury at 21 cm from the incisors was recognized (figure 1).
      There was erythema noted in the trachea at this level, but no evidence of
      transmural injury to the trachea. Figure 1Through-and-through gunshot wound to
      esophagus. Arrows denote areas of injury. What would you do?: Commence 14-day
      course of broad spectrum antibiotics.Endoscopic stenting with video-assisted
      thorascopic surgery (VATS) washout.Local exploration with wide drain
      placement.Open esophagectomy with spit fistula.

PMID- 30234168
TI  - Patient-reported outcomes in trauma: a scoping study of published research.
AB  - More people are surviving traumatic injury, but disability and reduced quality of
      life are frequent. Investigators are now focusing on patient-reported outcomes
      (PROs) to better understand this problem. We performed a scoping study of the
      literature to explore trends in the study of PROs after injury. The volume of
      published literature on PROs after injury has consistently increased, but use of
      measurement tool and categorization of publications are inconsistent. Journal
      keyword patterns are inconsistent and likely limit the effective dissemination of
      important findings. In studies of hospitalized trauma patients, more than 100
      unique measurement tools were used, and trauma-specific measures were used in
      fewer than 5% of studies. International investigators are more consistent than
      those in the USAin the use of validated, classic measurement tools such as the
      Short-Form 36 and the EuroQoL Five-Dimension tools. Uniform use of measurement
      tools would help improve the quality and comparability of research on PROs, and
      trauma-specific measures would enhance the study of long-term injury outcomes.

PMID- 30234169
TI  - 'CPR for Feet' care bundle to improve foot assessment in inpatient diabetes.
AB  - Aims: The Scottish Inpatient Diabetes Foot Audit conducted in 2013 revealed that
      57% of inpatients had not had their feet checked on admission, 60% of those at
      risk did not have pressure relief in place and 2.4% developed a new foot lesion.
      In response, the Scottish Diabetes Foot Action Group launched the 'CPR for Feet'
      campaign. The aim of this project was to raise awareness of the 'Check, Protect
      and Refer' (CPR) campaign as well as improve the assessment and management of
      inpatients with diabetes. Methods: A quality improvement project underpinned by
      Plan-Do-Study-Act (PDSA) methodology was undertaken. The first and second cycles
      focused on staff education and the implementation of a 'CPR for Feet' assessment
      checklist using campaign guidelines, training manuals and modules. The third and
      fourth cycles focused on staff feedback and the implementation of a 'CPR for
      Feet' care bundle. Results: Baseline measurements revealed 28% of patients had
      evidence of foot assessment. Medical and nursing staff reported to be largely
      unaware of the 'CPR for Feet' campaign (13%). Fifty-two per cent of inpatients
      with diabetes had their feet assessed and managed correctly following the second
      PDSA cycle. After completion of the third and fourth PDSA this number improved
      further to 72% and all staff reported to be aware of the campaign. Conclusions:
      The introduction of a 'CPR for Feet' care bundle improved the assessment of
      inpatients with diabetes.

PMID- 30234170
TI  - Decreasing birth asphyxia: utility of statistical process control in a low
      resource setting.
AB  - The neonatal period is a critical time for survival of the child. A
      disproportionate amount of neonatal deaths occur in low-resource countries and
      are attributable to perinatal events, especially birth asphyxia. This project
      aimed to reduce the incidence of birth asphyxia by 20% by June 2014 through
      training in neonatal resuscitation and improving the availability of
      resuscitation equipment in the delivery room in the National Hospital Abuja,
      Nigeria. A prospective, longitudinal study using statistical process control
      analytical methods was done enrolling babies delivered at the National Hospital
      Abuja. Low Apgar scores or birth asphyxia (defined a priori as any score <7 at 1,
      5 and/or at 10 min) was assessed. To ensure reliability and validity of Apgar
      scoring, trainings on scoring were held for labour and delivery staff.
      Interventions included provision of additional equipment and trainings on
      neonatal resuscitation. Apgar scores were aggregated weekly over 25 months.
      Control charts with three SE confidence limits were used to monitor the
      proportion of scores <=7. The baseline incidence of low Apgar scores, as defined
      a priori, was 33%, 17% and 10% while postintervention the incidence was 18%, 17%
      and 6% at 1, 5 and 10 min, respectively-a reduction of 45% and 40% in the 1-min
      and 10-min low Apgar scores. Increased communication, additional resuscitation
      equipment and training of delivery personnel on neonatal resuscitation are
      associated with reductions in measures of birth asphyxia. These improvements have
      been sustained and efforts are ongoing to spread our interventions to other
      special care delivery units/nursery in adjoining states. Our study demonstrates
      the feasibility and utility of using improvement science methods to assess and
      improve perinatal outcome in low-resource settings.

PMID- 30234171
TI  - Applying lean improvement methodology within a public health context:
      administration and organisation of a training programme.

PMID- 30234172
TI  - Optimisation of hyperemesis gravidarum management through an emergency department
      setting.
AB  - Hyperemesis gravidarum is a common condition characterised by severe nausea and
      vomiting. The referral process from the emergency department (ED) to obstetrics
      and gynaecology (O&G) can lead to treatment delays before the gynaecology team
      review the patient, resulting in unnecessary prolonged inpatient stays in O&G.
      This quality improvement project created a clinical pathway which optimised care
      of patients presenting with hyperemesis gravidarum in the ED at the Princess
      Royal University Hospital using a treatment protocol. Two audits were carried out
      to assess improvements in patient care and reduction in admissions to O&G.
      Overall, admissions to O&G were reduced by 68.7% (cycle 1) and 70.5% (cycle 2)
      compared with admission rates before the proforma, saving the trust an estimated
      L265 700 and 235 bed days over a year.

PMID- 30234173
TI  - ELECTIVIST: a novel system to improve elective caesarean section booking.
AB  - Elective caesarean sections (ELCS) vary widely in surgical complexity and are
      routinely performed between 39 and 40 weeks of pregnancy. Unselected ELCS lists
      may create clinical risk due to inappropriately complex case mixes and over
      running theatre time, impacting on emergency care. Despite evidence that ELCS
      list over-run is a widespread concern for many units, there is a paucity of
      literature regarding effective ELCS booking systems. We designed a novel ELCS
      risk scoring system, ELECTIVIST, comprising a risk assessment by the booking
      clinician and allocation of a complexity score to each case from 1 to 6. The
      maximum risk score for any one patient was 6, with a maximum total score on any
      one ELCS list of 6 and a maximum of three cases per list. We performed a
      retrospective analysis of all ELCS performed in our unit in 2016 using existing
      booking information and theatre data to assess existing case mix complexity and
      theatre over-run. This showed that 36% of ELCS lists were overbooked with
      inappropriately complex case mix and 21% of lists over-ran with 6% impacting on
      emergency obstetric theatres. Assessment of the impact of ELECTIVIST on ELCS
      capacity prior to implementation showed that no additional capacity was required
      to accommodate existing complexity. At 6 months following implementation, theatre
      over-run was reduced to 10% and over-run impacting on emergency theatre to 1%.
      The requirement for extra ELCS lists to accommodate capacity reduced by 66%.
      ELECTIVIST is a novel system that improves ELCS booking using existing capacity
      and reduces theatre list over-run. It is transferable, cost neutral and could be
      widely applied in obstetric units.

PMID- 30234174
TI  - Medical students as agents of change: a qualitative exploratory study.
AB  - Background: There is evidence that medical students have the potential to
      actively initiate, lead and bring about change through quality improvement within
      healthcare organisations. For effective change to occur, it is important that
      students are introduced to, and exposed to the value and necessity of quality
      improvement early in their careers. The aim of this study was to explore the
      perspectives and experiences of medical students and their mentors after
      undertaking quality improvement projects within the healthcare setting, and if
      such practice-based experiences were an effective way of building improvement
      capacity and changing practice. Methods: A qualitative interpretive description
      methodology, using focus groups with medical students and semi-structured
      interviews with academic and clinical mentors following completion of students' 4
      week quality improvement projects was adopted. Results: The findings indicate
      that there are a range of facilitators and barriers to undertaking and completing
      quality improvement projects in the clinical setting, such as time-scales,
      differing perspectives, roles and responsibilities between students and
      multidisciplinary healthcare professionals. Conclusions: This study has
      demonstrated that quality improvement experiential learning can develop knowledge
      and skills among medical students and transform attitudes towards quality
      improvement. Furthermore, it can also have a positive impact on clinical staff
      and healthcare organisations. Despite inherent challenges, undertaking quality
      improvement projects in clinical practice enhances knowledge, understanding and
      skills, and allows medical students to see themselves as important influencers of
      change as future doctors.

PMID- 30234175
TI  - Anxiety in children attending a specialist inherited cardiac arrhythmia clinic: a
      questionnaire study.
AB  - Objectives: Inherited cardiac arrhythmia syndromes are life-threatening
      conditions. There is a paucity of research examining the psychological impact of
      these conditions in children. This study had three main aims. The first was to
      explore how the Cardiac Anxiety Questionnaire (CAQ) performs in a child
      population. The second aim was to compare the level of anxiety of children with
      an inherited cardiac arrhythmia syndrome and children being screened due to a
      family history of an inherited cardiac arrhythmia syndrome to control children.
      The third aim was to examine associations between a sudden cardiac death in the
      immediate family and levels of anxiety. Method: 47 children with an inherited
      cardiac arrhythmia syndrome, 78 children with a family history and 75 control
      children completed the Revised Child Anxiety and Depression Scale (RCADS), the
      Cardiac Anxiety Questionnaire for Children (CAQ-C) and the Childhood Anxiety
      Sensitivity Index. Children were between the age of 8 and 16 years. Results: The
      study found the CAQ-C had promising psychometric properties. There were no
      significant differences in total anxiety scores (as measured by the RCADS)
      between the three groups. There were significant differences in cardiac-focused
      anxiety scores between the three groups. Conclusions: The CAQ has promising
      psychometric properties in a child population. However, further research is
      needed. Children attending specialist inherited cardiac arrhythmia clinics should
      be targeted for routine psychological screening and offered psychological
      intervention where necessary.

PMID- 30234176
TI  - Paediatric tuberculosis in Singapore: a retrospective review.
AB  - Background: Tuberculosis (TB) is a major cause of mortality and morbidity in the
      world. Each case represents ongoing transmission and has a significant public
      health burden. We aim to examine the clinical profile of paediatric TB and
      compare pulmonary TB (PTB) with extrapulmonary TB (EPTB) in Singapore. Methods: A
      retrospective study of patients admitted to KK Women's and Children's Hospital,
      Singapore from January 2008 to September 2017 with active TB was undertaken. The
      clinical characteristics and outcomes of patients with PTB and EPTB were
      compared. Results: Seventy-five patients were diagnosed as having active TB (49
      (65%) with PTB and 26 (35%) with EPTB). Patients with EPTB were more likely than
      those with PTB to be younger (median age 5.1 (IQR 1.2-10.2) years vs 10.1 (IQR
      3.5-13.5) years), immunodeficient (35% vs 6%), with a lower haemoglobin count
      (median 11.2 (IQR 10.2-11.9) g/dL vs 12.0 (IQR 10.5-13.9) g/dL), lower recovery
      rate (27% vs 57%) and required longer duration of treatment (median 12 (IQR 9-12)
      months vs 6 (IQR 6-9) months). Common clinical presentations of both PTB and EPTB
      were significant fever (27%), cough (33%) and weight loss (32%). Overall
      mortality was 8% with septic shock responsible for three of the six deaths.
      Conclusion: EPTB is more common in the younger age group and is associated with a
      lower recovery rate.

PMID- 30234177
TI  - Nocturnal enuresis in children from Santo Domingo, Dominican Republic: a
      questionnaire study of prevalence and risk factors.
AB  - Objective: To determine the prevalence of paediatric nocturnal enuresis in Santo
      Domingo, Dominican Republic. Design: A cross-sectional study was performed using
      a pretested questionnaire. Setting: Three different schools in Santo Domingo,
      Dominican Republic. Participants: 700 children aged 5-11 years attending one of
      the different schools in Santo Domingo, Dominican Republic. Intervention: The
      study was carried out from November 2017 to December 2017. Main outcome measures:
      Prevalence of nocturnal enuresis. Results: 700 questionnaires were sent to be
      filled and 682 were returned. 655 fully filled questionnaires met the
      requirements of the study. 183 children were identified with nocturnal enuresis
      among which 88 were boys and 95 were girls. Only 11% of children with enuresis
      sought medical help. The prevalence of nocturnal enuresis was 27.9%. No
      statistical significance was found between gender, order in the family,
      constipation and breast feeding (p>0.05). Age, deep sleep and family history of
      enuresis were strongly associated with nocturnal enuresis. Conclusions: The
      prevalence of nocturnal enuresis in Santo Domingo was found to be 27.9% and it
      was higher compared with some Asian countries but lower than Morocco and Jamaica.
      Only 11% of children with enuresis sought medical help. Nocturnal enuresis is an
      important problem in the paediatric population of Santo Domingo, but very few
      children receive treatment due to the financial costs of healthcare in the
      Dominican Republic.

PMID- 30234178
TI  - Vulnerability of farming communities to malaria in the Bole district, Ghana.
AB  - Malaria contributes substantially to the poor health situation in the northern
      region of Ghana, especially in the Bole district. This paper is an outcome of a
      study, which assessed the factors that influenced the vulnerability of farming
      households to malaria, as well as the economic burden of the malaria prevalence
      in the Bole District, Ghana. The multiple linear regression model was used to
      analyze the determinants of household's vulnerability to malaria, and to examine
      the relationship between the non-parametric dependent variable and dichotomous
      independent variables. The outcome of the study revealed an increase in malaria
      cases during the rainy season. Total direct cost of malaria care, number of
      people comprising the farming household, support for malaria prevention,
      information on mosquito breeding and development, and absenteeism from farm
      emerged as the main factors, which influenced the households' vulnerability to
      malaria. Direct and indirect costs of malaria treatment have negatively affected
      the households' budget. In addition, malaria treatment cost represented a
      substantial portion of poor farming household income. The direct cost was
      estimated to GH? 4059, and the indirect cost was estimated to GH? 4654. It was
      recommended to the government of Ghana to expand the National Malaria Control
      Program to the household level and make National Health Insurance Scheme more
      efficient.

PMID- 30234179
TI  - The Kaplan-Meier Method for Estimating and Comparing Proportions in a Randomized
      Controlled Trial with Dropouts.
AB  - We propose a method for estimating and comparing proportions of study
      participants who reached an event of interest during a randomized controlled
      trial. Standard methods for estimating this proportion include the intent-to
      treat method, which counts the number who reached the event of interest divided
      by the total number of participants, and the completers-only method, which counts
      the number who reached the event only among those who completed the entire study.
      When participants drop out of the study early, however, these methods will either
      be biased or inefficient. We propose to use the Kaplan-Meier method from survival
      analysis to estimate the proportion of interest in this non-survival setting. We
      show through extensive simulation studies that the Kaplan-Meier method has less
      bias and is more efficient than the standard methods. We demonstrate the
      performance of all methods for estimating proportions in one sample and for
      comparing proportions across two samples. Finally, we apply the proposed method
      to a data set for estimating and comparing proportions of patients who achieved
      treatment response during a Parkinson's disease trial for the treatment of
      impulse control disorders.

PMID- 30234182
TI  - The vitamin D level in umbilical cord blood in premature infants with or without
      intra-ventricular hemorrhage: A cross-sectional study.
AB  - Background: Intra-ventricular hemorrhage (IVH) is acute cerebral complications of
      premature infants which may lead to the long-term problems. Objective: According
      to the role of vitamin D in the stability of the blood vessels, the present study
      was carried out in order to compare the vitamin D level in the premature infants
      with or without IVH. Materials and Methods: This cross-sectional study was
      carried out on 180 premature infants in the Ghaem Hospital, Mashhad, Iran 97
      infants without IVH (53.9%) and 83 with IVH (46.1%) through convenience sampling
      technique in 2015-2017. Serum vitamin D level of funiculus in the two groups was
      compared. A researcher made questionnaire was used which includes infants'
      personal and laboratory information; and their mother's information. Results:
      Seventy nine percent of infants suffered from vitamin D deficiency in which 33.9%
      had a severe deficiency (less than 10 ng/ml), 30% moderate deficiency (10.1-20
      ng/ml), 15% slight deficiency (20.1-30 ng/ml) and 21.1% had normal vitamin D
      (>30.1 ng/ml). Vitamin D mean+/-SD of infants in the control group, 23.71+/-12.98
      ng/ml and case group 15.92+/-10.27 ng/ml (p<0.001). In total 92.8% of infants
      with IVH had levels of vitamin D below30 ng/ml, while this rate was 67% in
      infants without IVH. Conclusion: Vitamin D deficiency in the premature infants is
      very common. Also, the serum vitamin D level in infants with IVH was less than
      infants without IVH. Therefore, the recommendation of vitamin D may be effective
      in the prevention of neonatal IVH.

PMID- 30234180
TI  - Estimating the impact of structural directionality: How reliable are undirected
      connectomes?
AB  - Directionality is a fundamental feature of network connections. Most structural
      brain networks are intrinsically directed because of the nature of chemical
      synapses, which comprise most neuronal connections. Because of the limitations of
      noninvasive imaging techniques, the directionality of connections between
      structurally connected regions of the human brain cannot be confirmed. Hence,
      connections are represented as undirected, and it is still unknown how this lack
      of directionality affects brain network topology. Using six directed brain
      networks from different species and parcellations (cat, mouse, C. elegans, and
      three macaque networks), we estimate the inaccuracies in network measures
      (degree, betweenness, clustering coefficient, path length, global efficiency,
      participation index, and small-worldness) associated with the removal of the
      directionality of connections. We employ three different methods to render
      directed brain networks undirected: (a) remove unidirectional connections, (b)
      add reciprocal connections, and (c) combine equal numbers of removed and added
      unidirectional connections. We quantify the extent of inaccuracy in network
      measures introduced through neglecting connection directionality for individual
      nodes and across the network. We find that the coarse division between core and
      peripheral nodes remains accurate for undirected networks. However, hub nodes
      differ considerably when directionality is neglected. Comparing the different
      methods to generate undirected networks from directed ones, we generally find
      that the addition of reciprocal connections (false positives) causes larger
      errors in graph-theoretic measures than the removal of the same number of
      directed connections (false negatives). These findings suggest that
      directionality plays an essential role in shaping brain networks and highlight
      some limitations of undirected connectomes.

PMID- 30234181
TI  - Prevalence of Homologous Recombination-Related Gene Mutations Across Multiple
      Cancer Types.
AB  - Purpose: The prevalence of homologous recombination DNA damage repair (HR-DDR)
      deficiencies among all tumor lineages is not well characterized. Therapy directed
      toward homologous recombination DDR deficiency (HRD) is now approved in ovarian
      and breast cancer, and there may be additional opportunities for benefit for
      patients with other cancers. Comprehensive evaluations for HRD are limited in
      part by the lack of a uniform, cost-effective method for testing and defining
      HRD. Methods: Molecular profiles of 52,426 tumors were reviewed to identify
      pathogenic mutations in the HR-DDR genes ARID1A, ATM, ATRX, BAP1, BARD1, BLM,
      BRCA1/2, BRIP1, CHEK1/2, FANCA/C/D2/E/F/G/L, MRE11A, NBN, PALB2, RAD50, RAD51,
      RAD51B, or WRN. From solid tumors submitted to Caris Life Sciences, molecular
      profiles were generated using next-generation sequencing (NGS; average read
      depth, 500*). A total of 17,566 tumors were sequenced with NGS600 (n = 592
      genes), and 34,860 tumors underwent hotspot Illumina MiSeq platform testing (n =
      47 genes). Results: Of the tumors that underwent NGS600 testing, the overall
      frequency of HRDDR mutations detected was 17.4%, and the most commonly mutated
      lineages were endometrial (34.4%; n = 1,475), biliary tract (28.9%; n = 343),
      bladder (23.9%; n = 201), hepatocellular (20.9%; n = 115), gastroesophageal
      (20.8%; n = 619), and ovarian (20.0%; n = 2,489). Least commonly mutated lineages
      included GI stromal (3.7%; n = 108), head and neck (6.8%; n = 206), and sarcoma
      (9.3%; n = 592). ARID1A was the most commonly mutated gene (7.2%), followed by
      BRCA2 (3.0%), BRCA1 (2.8%), ATM (1.3%), ATRX (1.3%), and CHEK2 (1.3%).
      Conclusions: HR-DDR mutations were seen in 17.4% of tumors across 21 cancer
      lineages, providing a path to explore the role of HRD-directed therapies,
      including poly-ADP ribose polymerase inhibitors, DNA-damaging chemotherapies, and
      newer agents such as ATR inhibitors.

PMID- 30234183
TI  - Effect of senescence on some apoptosis and oxidative stress markers in infertile
      normozospermic and oligospermic men: A cross-sectional study.
AB  - Background: Male senescence may affect testicular function, sperm indices and
      generation of high levels of oxidants and apoptosis. Objective: This study
      evaluates the effect of male age on the expression of some apoptosis and
      oxidative stress markers in seminal fluid of males investigated for infertility
      in a tertiary health institution in Nigeria. Materials and Methods: In this cross
      sectional study, 122 men aged 20-60 yr who were investigated for infertility and
      were stratified according to age into four groups. Seminal plasma caspase 3,
      cytochrome C, and total antioxidant capacity (TAC) were assayed by ELISA
      technique, while manual semen analysis was performed according to WHO standard.
      Results: Seminal caspase 3, and cytochrome C activity increased while TAC and
      sperm indices decreased with increasing age. Cytochrome C (r=0.288; p=0.002) and
      caspase 3 (r=0.250; p=0.05) correlated significantly with age in normospermia
      while cytochrome C (r=0.314; p=0.02), caspase 3 (r=0.268; p=0.05), TAC (r=-0.342;
      p=0.01) and morphology percentage (r=-0.414; p=0.002) correlated with age in
      oligospermic infertile males. Conclusion: The measured apoptotic markers
      increased with increasing age while TAC and sperm indices decreased with
      increasing age of subjects evaluated. Although the levels of measured apoptosis
      and oxidative stress markers correlated with age in normozospermia, the effect on
      sperm indices was severe among oligospermia compare to normozospermia. Therefore,
      these markers may be assayed in aged men attending fertility clinics.

PMID- 30234184
TI  - Frequency of cytomegalovirus in fertile and infertile men, referring to
      Afzalipour Hospital IVF Research Center, Kerman, IRAN: A case-control study.
AB  - Background: Cytomegalovirus (CMV) virus can hide in urinary genital tract cells
      and affect male infertility disorders. Objective: To evaluate frequency of CMV in
      the semen samples of men with infertility problems referring to a in vitro
      fertilization (IVF) center in Kerman, Iran and its association with the
      parameters of semen. Materials and Methods: In this case-control study, Real time
      polymerase chain reaction test was performed for detection of human
      cytomegalovirus in 100 fertile men compared to 100 infertile men referred to the
      IVF center of Afzalipour Hospital, Kerman, Iran. Results: Out of 200 samples, 30
      samples (15%) were positive for CMV DNA virus (23/100 men (23%) in case group and
      7/100 men (7%) in the control group). Sperm counts and motility in the control
      group were more than the case group (p?0.0001). There was a significant
      relationship between the prevalence of CMV infection and male infertility
      (p?0.001). Conclusion: Our finding showed that, prevalence of CMV infection was
      higher in infertile men compared to fertile men and CMV infection can be
      considered as an important part of male infertility. So; antiviral treatment of
      positive cases can be effective in improving sperm quality and successful IVF.
      The relationship between CMV infection in semen and infertility was obtained in
      previous studies and was confirmed by our study.

PMID- 30234185
TI  - Protective effect of curcumin on fertility of rats after exposure to compact
      fluorescent lamps: An experimental study.
AB  - Background: Testicular function is modified by maturational gonadostatic control
      highly susceptible to negative physiologic niche-altering factors like UV-rays.
      Objective: This study was performed in order to uncover new aspects of Compact
      Florescent Lamps (CFLs) induced damages on the testicular tissue of rats and
      evaluating the effect of curcumin on testis of rats after exposure to compact
      florescent Lamps. Materials and Methods: Twenty-four adult male Albino rats were
      randomly divided into three groups: control group (ethyl oleate 0.2 ml, IP, for
      45 days, without CFLs exposure), fluorescent group (ethyl oleate 0.2 ml, IP,
      daily and treated with 12 hr CFLs exposure for 45 days) and curcumin group
      (curcumin 20 u M, IP along with 12 hr CFLs exposure for 45 days). The rats were
      anesthetized at the end of the experiment. Gonadotropin hormones and prolactin
      levels were measured; Histopathological and histomorphometrical analysis of the
      testis was carried out. Results: Results of this study showed that CFLs
      significantly decreased serum levels of follicle stimulating hormone, prolactin,
      testicular weight, sperm motility, TDI, and SPI. Furthermore, CFLs had no effect
      on serum levels of luteinizing hormone and sperm count and also, increased
      abnormal sperm shapes. Our results also showed that curcumin supplementation
      following CFLs reversed these alterations. Conclusion: These results strongly
      suggest that CFLs severely impairs testis while curcumin as an antioxidant had
      protective effects on undesirable effects in testis induced by CFLs.

PMID- 30234186
TI  - The association between estradiol levels and cognitive function in postmenopausal
      women.
AB  - Background: Levels of estradiol decreases as women arrive the menopausal
      transition and enter to a low, steady level during the early postmenopause. In
      addition, memory dysfunction are highly prevalent during this period. Objective:
      Our study was designed to determine whether endogenous levels of estradiol are
      related to cognitive function in postmenopausal. Materials and Methods: The cross
      sectional study was conducted between November 2015 to February 2016 on 209
      healthy postmenopausal women. The women filled out the Montreal Cognitive
      Assessment (MoCA) scale. Then, estradiol level was tested for association with
      cognitive function adjusted for factors supposed to confound this association.
      Results: The prevalence of cognitive dysfunction; MoCA points <=26 in our
      participants was 62.7%, and mean+/-SD of estradiol level was 14.92+/-10.24pg/ml
      in participants with cognitive dysfunction in comparison with 21.67+/-14.92pg/ml
      in those with normal cognitive function (p<0.001). There were significant
      association between MoCA points with estradiol level (p<0.001) and educational
      status (p<0.001). Conclusion: Estradiol replacement therapy in postmenopausal
      women with low endogenous estradiol levels and decreased cognitive function might
      be necessary.

PMID- 30234187
TI  - Is semen analysis without strict criteria misleading decisions in IVF? A
      prospective systematic study.
AB  - Background: Sperm morphology has been strongly linked to fertilization. This
      makes it an important component in semen analysis. They are usually assessed by
      world health organization (WHO) standard or Kruger strict criteria in in-vitro
      fertilization (IVF) centers all over the world. Sperm count, motility, and
      morphology together form the basis by which patients are allocated into IVF or
      intra-cytoplasmic sperm injection. Objective: This study aimed to compare
      fertilization rates in standard IVF from patients with normal sperm count and
      motility with and without morphological assessment by WHO guideline. Materials
      and Methods: In this prospective cohort study, sperm count, motility, and
      morphology of 504 men candidate for IVF program over a three years period in our
      center were evaluated in two groups: Group A (case group) included men with
      normal sperm count and motility but with a poor morphology and group B (control
      group) included men with normal sperm count, motility and morphology evaluated by
      WHO criteria. Fertilization rate in both groups were then analyzed after 16-18 hr
      post insemination. Results: Fertilization rate was higher in group B (p=0.028).
      Participants in group B, apart from having a normal sperm count (32.9+/-7.2) and
      motility (62.4+/-8.9), have a strict morphology of >=30%. Our result has shown
      that spermatozoa in group B had a higher fertilization rate (71.4%). Though the
      sperm count (36.4+/-6.7) and motility (66.3+/-7.4) in group A were slightly
      higher (p=0.058 and p=0.060 respectively) than group B, the fertilization rate
      was lower. Conclusion: Our study showed that sperm morphology could be a very
      important consideration before decisions towards allocation of patients into IVF
      or intra-cytoplasmic sperm injection.

PMID- 30234188
TI  - Upstream or swim up processing technique: which one is more effective to select
      human sperm with high chromatin integrity.
AB  - Background: Sperm processing methods separate motile sperms with good morphology
      from dead and abnormal forms of sperms, immature germ cells, and non-sperm cells.
      Objective: The propose of this study was to compare the efficacy of upstream and
      swim-up processing techniques to separate sperms with the high quality especially
      in relation to sperm chromatin integrity. Materials and Methods: This
      experimental study used semen samples from 60 normozoospermic men. Specimens were
      divided into equal aliquots for processing by swim up (group A), and upstream
      (group B) methods and compare with control by raw semen (group C). Sperm
      concentration, morphology, motility, DNA fragmentation and chromatin maturation
      were measured in these three groups. Results: The results revealed that sperm
      concentration in the swim up samples was significantly greater than upstream
      samples (p<=0.04). as addition, motile sperm recovery including the percentage of
      progressive motility and a total number of motile sperm was better in the swim-up
      compared to an upstream method and raw semen (p<=0.001). The cell debris and
      seminal fluid were equally removed by both methods and the percentage of normal
      forms was also similar in both procedures (p>=0.4). In addition, sperm DNA
      fragmentation and chromatin maturation were not significantly different between
      the three groups (p>=0.1). Conclusion: According to results, apparently the
      upstream method had no significant efficiency to separate good quality sperms
      compare to swim up. Therefore, swim up seems to be a simple, inexpensive,
      reliable and widely available method with an efficient yield to separate motile
      sperm with good morphology and better chromatin integrity for insemination in the
      infertility clinics.

PMID- 30234189
TI  - Assessing the prevalence of Staphylococcus aureus in infertile male patients in
      Tabriz, northwest Iran.
AB  - Background: Staphylococcus aureus is an infrequent, but one of the most
      successful bacteria that associated with infertility and are able to spermatozoa
      immobilization and agglutination. Objective: The aim of present study was to
      determine the frequency of S. aureus in semen obtained from infertile male
      patients in northwest Iran. Materials and Methods: Seminal fluids of 100
      infertile men were evaluated. Standard semen examination was done according to
      World Health Organization guidelines. After isolation and identification of S.
      aureus isolates according to reference methods, determination of susceptibility
      against important antibiotics and polymerase chain reaction were performed to
      identify mecA and tst genes. Results: Data obtained from the present study shows
      that 16% of infertile male patients were colonized by S. aureus. Ten (62.5%) of
      the individuals had abnormal seminal fluid sperm motility and morphology and
      three (18.8%) of them had an abnormal seminal fluid density, whereas after
      washing with albumin-saline declined to 5 (31.3%), 4 (25%) and 1 (6.3%),
      respectively. The antibiogram results showed that, except penicillin, other
      antibiotics have high activity on isolates. Regarding polymerase chain reaction
      results, mecA sequences were detected in 3 (18.7%) strains, whilst the tst gene
      encoding TSST-1 was not detected in any of clinical strains. Conclusion: It would
      appear that the S. aureus may be an additional negative factor worsening sperm
      quality and affecting male fertility. Therefore, it demands that all the patients
      attending in infertility treatment facilities be investigated thoroughly.

PMID- 30234190
TI  - Improving risk stratification for hospital mortality using troponin: is it time
      for a change of heart?

PMID- 30234191
TI  - Visceral leishmaniasis cyclical trends in Bihar, India - implications for the
      elimination programme.
AB  - Background: Visceral leishmaniasis (VL) is a vector-borne disease of public
      health importance in India, with the highest burden of disease in the states of
      Bihar, Jharkhand, West Bengal and Uttar Pradesh. The disease is currently
      targeted for elimination (annual incidence to less than one per 10,000
      population) using indoor residual spraying, active case detection and treatment.
      Historically the disease trend in India has been regarded as cyclical with case
      resurgence characteristically occurring every 15 years.  Understanding this
      pattern is essential if the VL elimination gains are to be sustained. To better
      understand the cyclical trends, annual climatic indicators including rainfall,
      temperature and humidity over time were compared with annual VL case incidence
      data.  Methods: Annual climate data (rainfall, average and maximum temperature
      and specific humidity) from 1956-2004 were used to identify potential factors
      influencing VL incidence.  Months relevant to the VL life-cycle were identified
      and defined (Monsoon, Sand-fly Peak, Pre-Sand-fly Peak and Annual) for analysis.
      The Kruskall-Wallis test was used to determine significant difference between
      categorical rainfall and VL incidence, whilst univariate negative binomial
      regression models were used to determine predictors of disease incidence.
      Results: The negative binomial regression model showed statistically significant
      associations (p <0.05) for VL incidence and maximum temperature, and average
      temperature, when considering annual and pre-sand fly peak time periods. No other
      associations between humidity, rainfall or temperature and VL incidence were
      detected (all values p >0.05).  Conclusion: The VL programme in Bihar has made
      significant progress in adopting best practices for improved treatment and vector
      control, with the aim to achieve VL elimination.  However, open access granular
      programme data for indoor residual spray activities and case detection is
      required to fully understand the role of climate in disease transmission and
      potential resurgence.

PMID- 30234192
TI  - A sulfur-free peptide mimic of surfactant protein B (B-YL) exhibits high in vitro
      and in vivo surface activities.
AB  - Background: Animal-derived surfactants containing surfactant proteins B (SP-B)
      and C (SP-C) are used to treat respiratory distress syndrome (RDS) in preterm
      infants. SP-B (79 residues) plays a pivotal role in lung function and the design
      of synthetic lung surfactant. Super Mini-B (SMB), a 41-residue peptide based on
      the N- and C-domains of SP-B covalently joined with a turn and two disulfides,
      folds as an alpha-helix hairpin mimicking the properties of these domains in SP
      B. Here, we studied 'B-YL', a 41-residue SMB variant that has its four cysteine
      and two methionine residues replaced by tyrosine and leucine, respectively, to
      test whether these hydrophobic substitutions produce a surface-active, alpha
      helix hairpin. Methods: Structure and function of B-YL and SMB in surfactant
      lipids were compared with CD and FTIR spectroscopy, and surface activity with
      captive bubble surfactometry and in lavaged, surfactant-deficient adult rabbits.
      Results: CD and FTIR spectroscopy of B-YL in surfactant lipids showed secondary
      structures compatible with peptide folding as an alpha-helix hairpin, similar to
      SMB in lipids. B-YL in surfactant lipids demonstrated excellent in vitro surface
      activity and good oxygenation and dynamic compliance in lavaged, surfactant
      deficient adult rabbits, suggesting that the four tyrosine substitutions are an
      effective replacement for the disulfide-reinforced helix-turn of SMB. Here, the B
      YL fold may be stabilized by a core of clustered tyrosines linking the N- and C
      helices through non-covalent interactions involving aromatic rings. Conclusions:
      'Sulfur-free' B-YL forms an amphipathic helix-hairpin in surfactant liposomes
      with high surface activity and is functionally similar to SMB and native SP-B.
      The removal of the cysteines makes B-YL more feasible to scale up production for
      clinical application. B-YL's possible resistance against free oxygen radical
      damage to methionines by substitutions with leucine provides an extra edge over
      SMB in the treatment of respiratory failure in preterm infants with RDS.

PMID- 30234193
TI  - Developing new health technologies for neglected diseases: a pipeline portfolio
      review and cost model.
AB  - Background:  Funding for product development for neglected diseases fell from
      2009-2015, other than a short-term injection of Ebola funding. One impediment to
      mobilizing resources is a lack of information on product candidates, the
      estimated costs to move them through the pipeline, and the likelihood of specific
      launches. This study aimed to help fill these information gaps. Methods: We
      conducted a pipeline portfolio review to identify current candidates for 35
      neglected diseases. Using an adapted version of the Portfolio to Impact (P2I)
      financial modelling tool, we estimated the costs to move these candidates through
      the pipeline over the next decade and the likely launches. Since the current
      pipeline is unlikely to yield several critical products, we estimated the costs
      to develop a set of priority "missing" products. Results: We found 685 product
      candidates for neglected diseases as of August 31, 2017; 538 candidates met
      inclusion criteria for input into the model. It would cost about $16.3 billion
      (range $13.4-19.8B) to move these candidates through the pipeline, with three
      quarters of the costs incurred in the first 5 years, resulting in about 128 (89
      160) expected product launches.  Based on the current pipeline, there would be
      very few launches of complex new chemical entities; launches of highly
      efficacious vaccines for HIV, tuberculosis, or malaria would be unlikely.
      Estimated additional costs to launch one of each of 18 key missing products range
      from $13.6B-$21.8B, depending on product complexity. Over the next 5 years, total
      estimated costs to move current candidates through the pipeline and develop these
      18 missing products would be around $4.5-5.8B/year. Conclusions: Since current
      annual global spending on product development is about $3B, this study suggests
      the annual funding gap over the next 5 years is at least $1.5-2.8B, which is
      probably an underestimate. The current portfolio is not balanced across health
      needs.

PMID- 30234194
TI  - Funding global health product R&D: the Portfolio-To-Impact Model (P2I), a new
      tool for modelling the impact of different research portfolios.
AB  - Background: The Portfolio-To-Impact (P2I) Model is a novel tool, developed to
      estimate minimum funding needs to accelerate health product development from late
      stage preclinical study to phase III clinical trials, and to visualize potential
      product launches over time. Methods: A mixed methods approach was used.
      Assumptions on development costs at each phase were based on clinical trial costs
      from Parexel's R&D cost sourcebook. These were further refined and validated by
      interviews, with a wide variety of stakeholders from Product Development
      Partnerships, biopharmaceutical and diagnostic companies, and major funders of
      global health R&D. Results: the tool was used to create scenarios describing the
      impact, in terms of products developed, of different product portfolios with
      funding ranging from $1 million per annum through to $500 million per annum.
      These scenarios for a new global financing mechanism have been previously
      presented in a report setting out the potential for a new fund for research and
      development which would assist in accelerating product development for the
      diseases of poverty.  Conclusion: The P2I tool does enable a user to model
      different scenarios in terms of cost and number of health products launched when
      applied to a portfolio of health products.  The model is published as open access
      accompanied with a user guide.  The design allows it to be adapted and used for
      other health R&D portfolio analysis as described in an accompanying publication
      focussing on the pipeline for neglected diseases in 2017. We aim to continually
      refine and improve the model and we ask users to provide us with their own inputs
      that can help us update key parameters and assumptions.  We hope to catalyse
      users to adapt the model in ways that can increase its value, accuracy, and
      applications.

PMID- 30234195
TI  - Metabolic profiles derived from residual blood spot samples: A longitudinal
      analysis.
AB  - Background: Secondary use of newborn screening dried blood spot samples include
      use for biomedical or epidemiological research. However, the effects of storage
      conditions on archival samples requires further examination. The objective of
      this study was to determine the utility of residual newborn samples for deriving
      reliable metabolic gestational age estimates. Methods: Residual newborn dried
      blood spot samples that had been stored for 2-, 4-, 6-, or 12-months in
      temperature controlled (21 degrees C) conditions were re-analyzed for the full
      panel of newborn screening analytes offered by a provincial newborn screening lab
      in Ottawa, Canada. Data from re-analyzed samples were compared to corresponding
      baseline newborn screening values for absolute agreement, and Pearson and
      intraclass correlation. Performance of a gestational age estimation algorithm
      originally developed from baseline newborn screening values was then validated on
      data derived from stored samples. Results: A total of 307 samples were used for
      this study. 17-hydroxyprogesterone and newborn hemoglobin profiles measured by
      immunoassay and high-performance liquid chromatography, respectively, were among
      the most stable markers across all time points of analysis. Acylcarnitines
      exhibited the greatest degree of variation in stability upon repeat measurement.
      The largest shifts in newborn analyte profiles and the poorest performance of
      metabolic gestational age algorithms were observed when samples were analyzed 12
      months after sample collection. Conclusions: Duration of sample storage,
      independent of temperature and humidity, affects newborn screening profiles and
      gestational age estimates derived from metabolic gestational dating algorithms.
      When considering use of dried blood spot samples either for clinical or research
      purposes, care should be taken when interpreting data stemming from secondary
      use.

PMID- 30234196
TI  - Slaying little dragons: the impact of the Guinea Worm Eradication Program on
      dracunculiasis disability averted from 1990 to 2016.
AB  - Background: The objective of this study was to document the worldwide decline of
      dracunculiasis (Guinea worm disease, GWD) burden, expressed as disability
      adjusted life years (DALYs), from 1990 to 2016, as estimated in the Global Burden
      of Disease study 2016 (GBD 2016). While the annual number of cases of GWD have
      been consistently reported by WHO since the 1990s, the burden of disability due
      to GWD has not previously been quantified in GBD. Methods: The incidence of GWD
      was modeled for each endemic country using annual national case reports. A
      literature search was conducted to characterize the presentation of GWD,
      translate the clinical symptoms into health sequelae, and then assign an average
      duration to the infection. Prevalence measures by sequelae were multiplied by
      disability weights to estimate DALYs. Results: The total DALYs attributed to GWD
      across all endemic countries (n=21) in 1990 was 50,725 (95% UI: 35,265-69,197)
      and decreased to 0.9 (95% UI: 0.5-1.4) in 2016. A cumulative total of 12,900
      DALYs were attributable to GWD from 1990 to 2016. Conclusions: Using 1990
      estimates of burden propagated forward, this analysis suggests that between
      990,000 to 1.9 million DALYs have been averted as a result of the eradication
      program over the past 27 years.

PMID- 30234197
TI  - DataPackageR: Reproducible data preprocessing, standardization and sharing using
      R/Bioconductor for collaborative data analysis.
AB  - A central tenet of reproducible research is that scientific results are published
      along with the underlying data and software code necessary to reproduce and
      verify the findings. A host of tools and software have been released that
      facilitate such work-flows and scientific journals have increasingly demanded
      that code and primary data be made available with publications. There has been
      little practical advice on implementing reproducible research work-flows for
      large 'omics' or systems biology data sets used by teams of analysts working in
      collaboration. In such instances it is important to ensure all analysts use the
      same version of a data set for their analyses. Yet, instantiating relational
      databases and standard operating procedures can be unwieldy, with high "startup"
      costs and poor adherence to procedures when they deviate substantially from an
      analyst's usual work-flow. Ideally a reproducible research work-flow should fit
      naturally into an individual's existing work-flow, with minimal disruption. Here,
      we provide an overview of how we have leveraged popular open source tools,
      including Bioconductor, Rmarkdown, git version control, R, and specifically R's
      package system combined with a new tool DataPackageR, to implement a lightweight
      reproducible research work-flow for preprocessing large data sets, suitable for
      sharing among small-to-medium sized teams of computational scientists. Our
      primary contribution is the DataPackageR tool, which decouples time-consuming
      data processing from data analysis while leaving a traceable record of how raw
      data is processed into analysis-ready data sets. The software ensures packaged
      data objects are properly documented and performs checksum verification of these
      along with basic package version management, and importantly, leaves a record of
      data processing code in the form of package vignettes. Our group has implemented
      this work-flow to manage, analyze and report on pre-clinical immunological trial
      data from multi-center, multi-assay studies for the past three years.

PMID- 30234198
TI  - Market penetration of Xpert MTB/RIF in high tuberculosis burden countries: A
      trend analysis from 2014 - 2016.
AB  - Background: Xpert(r) MTB/RIF, a rapid tuberculosis (TB) molecular test, was
      endorsed by the World Health Organization in 2010. Since then, 34.4 million
      cartridges have been procured under concessional pricing. Although the roll out
      of this diagnostic is promising, previous studies showed low market penetration.
      Methods: To assess 3-year trends of market penetration of Xpert MTB/RIF in the
      public sector, smear and Xpert MTB/RIF volumes for the year 2016 were assessed
      and policies from 2014-2016 within 22 high-burden countries (HBCs) were studied.
      A structured questionnaire was sent to representatives of 22 HBCs. The
      questionnaires assessed the total smear and Xpert MTB/RIF volumes, number of
      modules and days of operation of GeneXpert machines in National TB Programs
      (NTPs). Data regarding the use of NTP GeneXpert machines for other diseases and
      GeneXpert procurement by other disease control programs were collected. Market
      penetration was estimated by the ratio of total sputum smear volume for initial
      diagnosis divided by the number of Xpert MTB/RIF tests procured in the public
      sector. Results: The survey response rate was 21/22 (95%). Smear/Xpert ratios
      decreased in 17/21 countries and increased in four countries, since 2014. The
      median ratio decreased from 32.6 (Q1:14.3, Q3: 58.9) in 2014 to 6.0 (Q1: 1.6, Q3:
      17.0) in 2016. Nineteen countries (19/19; 100%) were not using GeneXpert machines
      to their full capacity, however seven countries (7/19; 37%) were running tests
      for other diseases on their NTP-procured GeneXpert systems in 2017, such as HIV,
      hepatitis-C virus (HCV), Chlamydia trachomatis, and Neisseria gonorrhoeae. Five
      (5/15; 33%) countries reported GeneXpert procurement by HIV or HCV programs in
      2016 and/or 2017. Conclusions: Our results show a positive trend for Xpert
      MTB/RIF market penetration in 21 HBC public sectors. However, GeneXpert machines
      were under-utilized for TB, and inadequately exploited as a multi disease
      technology.

PMID- 30234200
TI  - Rhodium at the chemistry-biology interface.
AB  - As a rare element with no known natural biological function, rhodium has a
      limited history in biological chemistry and chemical biology. However, rhodium
      complexes have unique structure and reactivity attributes, and chemists have
      increasingly used these attributes to probe and perturb living systems. This
      brief review focuses on recent advances in the use of rhodium complexes in
      biological contexts, including medicinal chemistry, protein science, and chemical
      biology. In particular, we highlight both structure- and reactivity-driven
      approaches to biological probes and discuss how coordination environment affects
      molecular properties in a biological environment.

PMID- 30234199
TI  - STAT3 Knockdown Induces Tumor Formation by MDA-MB-231 Cells.
AB  - STAT3 plays a central role in oncogenesis by mediating cell survival, growth, and
      differentiation. It is constitutively activated in breast cancer. We investigated
      the role of STAT3 in tumor development by knocking down STAT3 levels in MDA-MB
      231 triple negative breast cancer cells using short hairpin RNA. The tumor
      forming potential of these STAT3-depleted cells was assessed by xenografts in
      immunocompromised NOD SCID mice. Contrary to its accepted tumor promoting role,
      we found STAT3 to be a negative regulator of growth in MDA-MB-231- derived
      tumors. Although similar observations have been made in thyroid carcinoma and
      lung adenocarcinoma xenograft studies, our novel results showed for the first
      time that the role of STAT3 in promoting tumorigenesis may be context-specific,
      and that STAT3 may actually be a negative regulator of certain breast-cancer
      types. Studies to identify the mechanisms of STAT3's negative regulatory role may
      be useful in developing STAT3-based therapeutics.

PMID- 30234201
TI  - Recent advances in the syntheses and properties of polynitrogen pentazolate anion
      cyclo-N5- and its derivatives.
AB  - The pentazolate anion, or cyclo-N5-, which is a five-membered ring composed
      solely of nitrogen atoms, has a unique structure among polynitrogen compounds.
      Cyclo-N5- is receiving ever-increasing levels of attention because of its
      potential ability to store large amounts of energy compared to the azide ion, its
      environmentally friendly decomposition products, and its carbon- and hydrogen
      free composition, which are promising characteristics for advancing the field of
      high-energy-density materials (HEDMs), that include explosives, oxidisers, and
      propellants in closed environments. In this review, we provide a detailed
      introduction to cyclo-N5- and cover the following topics: (1) substituted
      pentazoles as precursors of cyclo-N5-, with a focus on the syntheses and
      stabilities of substituted pentazole derivatives; (2) routes to cyclo-N5- through
      cleavage of C-N bonds in substituted pentazoles, during which competitive
      reactions between pentazole decomposition and C-N bond cleavage need to be
      considered to ensure a successful outcome; (3) complexes of cyclo-N5-,
      summarising recent progress toward producing cyclo-N5--based complexes through
      the assembly of isolated cyclo-N5- with both metallic and nonmetallic components;
      and (4) interactions between cyclo-N5- and metal cations and non-metal species,
      as well as factors that influence the stability of these complexes; in
      particular, the thermal stabilities of prepared cyclo-N5- salts are discussed.
      This review summarises recent studies and is intended to improve the
      understanding of polynitrogen chemistry while supporting further research into
      its potential application as an efficient, safe, and environmentally friendly
      HEDM.

PMID- 30234202
TI  - Carbon nitrides and metal nanoparticles: from controlled synthesis to design
      principles for improved photocatalysis.
AB  - The use of sunlight to drive chemical reactions via photocatalysis is of
      paramount importance towards a sustainable future. Among several photocatalysts,
      earth-abundant polymeric carbon nitride (PCN, often wrongly named g-C3N4) has
      emerged as an attractive candidate due to its ability to absorb light efficiently
      in the visible and near-infrared ranges, chemical stability, non-toxicity,
      straightforward synthesis, and versatility as a platform for constructing hybrid
      materials. Especially, hybrids with metal nanoparticles offer the unique
      possibility of combining the catalytic, electronic, and optical properties of
      metal nanoparticles with PCN. Here, we provide a comprehensive overview of PCN
      materials and their hybrids, emphasizing heterostructures with metal
      nanoparticles. We focus on recent advances encompassing synthetic strategies,
      design principles, photocatalytic applications, and charge-transfer mechanisms.
      We also discuss how the localized surface plasmon resonance (LSPR) effect of some
      noble metals NPs (e.g. Au, Ag, and Cu), bimetallic compositions, and even non
      noble metals NPs (e.g., Bi) synergistically contribute with PCN in light-driven
      transformations. Finally, we provide a perspective on the field, in which the
      understanding of the enhancement mechanisms combined with truly controlled
      synthesis can act as a powerful tool to the establishment of the design
      principles needed to take the field of photocatalysis with PCN to a new level,
      where the desired properties and performances can be planned in advance, and the
      target material synthesized accordingly.

PMID- 30234203
TI  - Single-cell mobility shift electrophoresis reports protein localization to the
      cell membrane.
AB  - While profiling of cell surface receptors grants valuable insight on cell
      phenotype, surface receptors alone cannot fully describe activated downstream
      signaling pathways, detect internalized receptor activity, or indicate
      constitutively active signaling in subcellular compartments. To measure surface
      bound and intracellular targets in the same cell, we introduce a tandem single
      cell assay that combines immunofluorescence of surface-bound epithelial cellular
      adhesion molecule (EpCAM) with subsequent protein polyacrylamide gel
      electrophoresis (PAGE) of unfixed MCF7 breast cancer cells. After surface
      staining and cell lysis, surface EpCAM is analyzed by single-cell PAGE,
      concurrent with immunoprobing of intracellular targets. Consequently, the single
      cell electrophoresis step reports localization of both surface and intracellular
      targets. Unbound intracellular EpCAM is readily resolved from surface EpCAM
      immunocomplex owing to a ~30% mobility shift. Flow cytometry and
      immunofluorescence are in concordance with single-cell PAGE. Lastly, we
      challenged the stability of the EpCAM immunocomplexes by varying ionic and non
      ionic component concentrations in the lysis buffer, the lysis time, and
      electrophoresis duration. As expected, the harsher conditions proved most
      disruptive to the immunocomplexes. The compatibility of live-cell immunostaining
      with single-cell PAGE eliminates the need to perform single-cell imaging by
      condensing read-out of both surface-bound proteins (as low mobility immune
      complexes) and intracellular targets to a single immunoblot, thus linking cell
      type and state.

PMID- 30234204
TI  - Intrinsic structure of pentapeptide Leu-enkephalin: geometry optimization and
      validation by comparison of VSCF-PT2 calculations with cold ion spectroscopy.
AB  - The intrinsic structure of an opioid peptide [Ala2, Leu5]-leucine enkephalin
      (ALE) has been investigated using first-principles based vibrational self
      consistent field (VSCF) theory and cold ion spectroscopy. IR-UV double resonance
      spectroscopy revealed the presence of only one highly abundant conformer of the
      singly protonated ALE, isolated and cryogenically cooled in the gas phase. High
      level quantum mechanical calculations of electronic structures in conjunction
      with a systematic conformational search allowed for finding a few low-energy
      candidate structures. In order to identify the observed structure, we computed
      vibrational spectra of the candidate structures and employed the theory at the
      semi-empirically scaled harmonic level and at the first-principles based
      anharmonic VSCF levels. The best match between the calculated "anharmonic" and
      the measured spectra appeared, indeed, for the most stable candidate. An average
      of two spectra calculated with different quantum mechanical potentials is
      proposed for the best match with experiment. The match thus validates the
      calculated intrinsic structure of ALE and demonstrates the predictive power of
      first-principles theory for solving structures of such large molecules.

PMID- 30234205
TI  - Novel N6 trisbidentate ligand coordinated Ir(iii) complexes and their Ru(ii)
      analogs.
AB  - Novel N6-coordinated Ir(iii) complexes bearing polypyridyl ligands were
      synthesized and characterized. In comparison to their Ru(ii) analogs, these
      Ir(iii) complexes showed blue-shifted UV-vis absorption and emission spectra, but
      dramatically increased triplet lifetimes with much broader and stronger triplet
      excited-state absorption.

PMID- 30234206
TI  - Prompting peroxidase-like activity of gold nanorod composites by localized
      surface plasmon resonance for fast colorimetric detection of prostate specific
      antigen.
AB  - The interaction between incident light and surface electrons in conductive
      nanoparticles produces localized plasmon oscillations with a resonant frequency
      that strongly depends on the composition, size, geometry, and dielectric
      environment. Hybrid heterostructure materials combining two or more materials in
      one structure represent a powerful way to achieve unique properties and
      multifunctionality compared to those of the individual nanoparticle components.
      Hybrid gold nanorods and gold nanoclusters (GNR/AuNCs) heterostructures prepared
      by intimate integration of GNRs with AuNCs exhibit both localized surface plasmon
      resonance (LSPR) property and peroxidase-like activity. It is found that the
      catalytic activity of the AuNC/GNR heterostructure could be remarkably enhanced
      by LSPR induced by photon-plasmon coupling in the visible to near-infrared (NIR)
      region. Meanwhile, the catalytic activity of enzyme-like AuNC/GNRs may be
      regulated by immunoreactions to realize specific recognition of a target analyte.
      Accordingly, a fast colorimetric assay within 5 min for the detection of prostate
      specific antigen (PSA) was developed based on a AuNC/GNRs heterostructure mask
      regulated by the target molecule under photon-plasmon coupling. The color
      intensity is inversely proportional to the PSA concentration, and quantitative
      analysis may be achieved in a range of 10 and 200 pg mL-1. This sensor was
      practically applied to detect PSA levels in prostate cancer serum samples and the
      determined values agreed well with those measured by the hospital using standard
      methods. This indicates that the AuNC/GNRs heterostructure-based assay has high
      accuracy for the analysis of practical samples. Moreover, the new method has the
      advantages of very fast determination and low sample volume requirements.

PMID- 30234207
TI  - Proton transfer in guanine-cytosine base pair analogues studied by NMR
      spectroscopy and PIMD simulations.
AB  - It has been hypothesised that proton tunnelling between paired nucleobases
      significantly enhances the formation of rare tautomeric forms and hence leads to
      errors in DNA replication. Here, we study nuclear quantum effects (NQEs) using
      deuterium isotope-induced changes of nitrogen NMR chemical shifts in a model base
      pair consisting of two tautomers of isocytosine, which form hydrogen-bonded
      dimers in the same way as the guanine-cytosine base pair. Isotope effects in NMR
      are consequences of NQEs, because ro-vibrational averaging of different
      isotopologues gives rise to different magnetic shielding of the nuclei. The
      experimental deuterium-induced chemical shift changes are compared with those
      calculated by a combination of path integral molecular dynamics (PIMD)
      simulations with DFT calculations of nuclear shielding. These calculations can
      directly link the observable isotope-induced shifts with NQEs. A comparison of
      the deuterium-induced changes of 15N chemical shifts with those predicted by PIMD
      simulations shows that inter-base proton transfer reactions do not take place in
      this system. We demonstrate, however, that NMR isotope shifts provide a unique
      possibility to study NQEs and to evaluate the accuracy of the computational
      methods used for modelling quantum effects in molecules. Calculations based on
      the PBE functional from the general-gradient-approximation family provided
      significantly worse predictions of deuterium isotope shifts than those with the
      hybrid B3LYP functional.

PMID- 30234208
TI  - Cu and Zn interactions with Abeta peptides: consequence of coordination on
      aggregation and formation of neurotoxic soluble Abeta oligomers.
AB  - The coordination chemistry of transition metal ions (Fe, Cu, Zn) with the amyloid
      beta (Abeta) peptides has attracted a lot of attention in recent years due to its
      repercussions in Alzheimer's disease (AD). Abeta peptide undergoes self
      aggregation to form amyloid plaques and soluble oligomers, which are believed to
      play a central role in AD pathology. Metal ions and Abeta-metal adducts can
      generate toxic radical species capable of modifying biomolecules, ultimately
      causing death of the neuronal cells. The impact of these metal ions on Abeta
      aggregation and neurotoxic species formation is still not well understood. A
      large number of reports indicate that transition metal ions such as Cu and Zn
      have significant effects on Abeta peptide aggregation and stabilization of
      neurotoxic soluble Abeta aggregates; some of these reports are contradictory too.
      A review on the effects of Cu and Zn metal ions on Abeta peptide aggregation due
      to their coordination with these peptides is presented herein. The review
      includes brief discussions with regards to the levels of Cu and Zn in an AD
      affected brain, structures of Abeta peptides, and the coordination of Abeta
      peptides with Cu and Zn. In the current scenario, a consensus appears to be
      emerging regarding the coordination mode and the effect of metal ions (especially
      Cu and Zn) on the aggregation of Abeta peptides. Towards the end, a short
      discussion on current research trends in the field of bifunctional metal
      chelators for tackling the metal effect on Abeta aggregation and toxicity has
      also been presented. It is expected that this review would aid in gaining a
      better understanding of the current status of various aspects of AD from an
      inorganic chemistry perspective.

PMID- 30234209
TI  - On the gas-phase formation of the HCO- anion: accurate quantum study of the H- +
      CO radiative association and HCO radiative electron attachment.
AB  - The hydrogen anion has never been observed in the interstellar medium, but it is
      most likely present in some interstellar regions. Since direct detection appears
      especially difficult, improving the knowledge of the astrochemical processes
      involving this anion should be valuable in defining a way of indirect detection.
      We present the first study of the radiative association of H- and CO to form the
      HCO- anion within a quantum time-independent approach. We use a state-of-the-art
      potential energy surface which has been calculated for the present study. The
      calculated radiative association rate coefficient is monotonically decreasing
      from 6 * 10-16 to 5 * 10-19 cm3 per molecule per s across the 0.01-1000 K
      temperature range. At the typical temperature of the cold interstellar medium,
      ~10 K, the radiative association rate is ~2 * 10-17 cm3 per molecule per s. On
      the other hand, the plane wave approximation is used to calculate the HCO
      radiative electron attachment rate coefficient. It is found to be almost constant
      and also equal to 2 * 10-17 cm3 per molecule per s. Setting aside the question of
      the abundances of the reactants of both processes, these results demonstrate that
      among the two gas-phase modes of production of the HCO- anion in cold
      interstellar medium considered in this study, the H- + CO radiative association
      is dominating below 10 K while the radiative electron attachment rate is larger
      above 10 K.

PMID- 30234210
TI  - Disentangling the complex spectrum of the ethynyl cation.
AB  - The ethynyl cation, C2H+, is of great importance in astrophysical media and in
      combustion. It is involved in the formation of larger organic compounds and in
      their decomposition mechanisms. Here, we investigate the low-lying electronic
      states of this cation using pure ab initio methodologies. The evolution of its
      potential energy surfaces along the stretching and bending coordinates reveals a
      high density of electronic states that favours mutual interactions and the mixing
      of wavefunctions. The ground state is of 3Pi space symmetry and the lowest
      singlet state (1Pi) is found to be a quasi-linear-quasi-linear Renner-Teller
      system. Our work suggests that the (spin-)rovibronic spectrum of such a molecular
      system is complicated, because of the contributions of multiple couplings,
      including Renner-Teller, vibronic and spin-orbit. We also deduced the adiabatic
      ionization energy of the ethynyl radical, in good agreement with recent
      measurements. In summary, our work shows that the ethynyl cation, in spite of its
      small size, still represents a challenging molecular problem to be solved.

PMID- 30234211
TI  - Properties of Feshbach and "shape"-resonances in ozone and their role in
      recombination reactions and anomalous isotope effects.
AB  - Computational modelling of recombination reactions that form ozone require the
      inclusion of several quantum mechanical effects such as symmetry, zero-point
      energy, scattering resonances and tunneling. Major elements of theory for
      rigorous description of this process are reviewed, with emphasis on interpreting
      the famous anomalous isotope effect due to substitutions of 18O. Three reaction
      pathways, for the formation of symmetric and asymmetric isotopologues of ozone,
      are introduced and a hierarchy of theory levels is outlined. Lower levels of
      theory are used to account for the effects of symmetry, isotope mass, rotational
      excitations and vibrational zero-point energy differences. They happen to be
      equivalent to statistical descriptions of the process and do not show anomalous
      isotope effects. Properties of scattering resonances should be included at the
      next level of theory, and may finally explain the isotope effect. Shape
      resonances, trapped behind the centrifugal barrier and populated by tunneling,
      can be studied by neglecting couplings between the diabatic ro-vibrational states
      of the system. Inclusion of these couplings enables the formation of Feshbach
      resonances. Accurate calculations using hyper-spherical coordinates are performed
      to obtain resonance energies, lifetimes and wavefunctions. Differences between
      the shape resonances and Feshbach resonances are emphasized.

PMID- 30234217
TI  - Collisional relaxation kinetics for ortho and para NH2- under photodetachment in
      cold ion traps.
AB  - The collisional cooling of the internal rotational states of the nonlinear anion
      NH2- (1A1), occurring at the low temperature of a cold ion trap under helium
      buffer gas cooling, is examined via quantum dynamics calculations and ion decay
      rate measurements. The calculations employ a novel ab initio potential energy
      surface that describes the interaction anisotropy and range of action between the
      molecular anions and the neutral He atoms. The state changing integral cross
      sections are employed to obtain the state-to-state rate coefficients, separately
      for the ortho- and the para-NH2- ions. These rates are in turn used to compute
      the state population evolution in the trap for both species, once photodetachment
      by a laser is initiated in the trap. The present work shows results for the
      combined losses of both species after the photodetachment laser is switched on
      and analyzes the differences of loss kinetics between the two hyperfine isomers.

PMID- 30234218
TI  - Electron-driven proton transfer enables nonradiative photodeactivation in
      microhydrated 2-aminoimidazole.
AB  - 2-Aminoimidazole (2-AIM) was proposed as a plausible nucleotide activating group
      in a nonenzymatic copying and polymerization of short RNA sequences under
      prebiotically plausible conditions. One of the key selection factors controlling
      the lifespan and importance of organic molecules on early Earth was ultraviolet
      radiation from the young Sun. Therefore, to assess the suitability of 2-AIM for
      prebiotic chemistry, we performed non-adiabatic molecular dynamics simulations
      and static explorations of potential energy surfaces of the photoexcited 2-AIM
      (H2O)5 model system by means of the algebraic diagrammatic construction method to
      the second order [ADC(2)]. Our quantum mechanical simulations demonstrate that
      1pisigma* excited states play a crucial role in the radiationless deactivation of
      the UV-excited 2-AIM-(H2O)5 system. More precisely, electron-driven proton
      transfer (EDPT) along water wires is the only photorelaxation pathway leading to
      the formation of 1pisigma*/S0 conical intersections. The availability of this
      mechanism and the lack of destructive photochemistry indicate that microhydrated
      2-AIM is characterized by substantial photostability and resistance to prolonged
      UV irradiation.

PMID- 30234223
TI  - Metal- and base-free synthesis of functionalized alpha,alpha-difluoroimines via
      electrophilic fluorination of N-substituted enamines.
AB  - A metal- and base-free synthesis of functionalized alpha,alpha-difluoroimines is
      presented. The reaction features mild conditions, high E/Z control and broad
      functional group tolerance. The utility of the products was demonstrated through
      valuable synthetic transformations.

PMID- 30234224
TI  - Atom-economic synthesis of cyclobuta[a]naphthalen-4-ols via a base-promoted [2 +
      2] cycloaddition/1,6-nucleophilic addition cascade.
AB  - A first atom-economic [2 + 2] cycloaddition/1,6-conjugate addition cascade of yne
      allenones with C-nucleophiles including 1,3-dicarbonyls and alpha,alpha
      dicyanoolefins under base-promoted conditions has been established, enabling the
      direct construction of C(sp3)-C(sp3) bonds to generate cyclobuta[a]naphthalen-1
      ols with generally good yields. These resulting products have a cyclobutene unit
      that contains both an aryl and alkyl group.

PMID- 30234226
TI  - The Pan-African Society of Cardiology position paper on reproductive healthcare
      for women with rheumatic heart disease.
AB  - This position paper summarises the current knowledge on the epidemiology,
      diagnosis and management of women of childbearing age with rheumatic heart
      disease (RHD) in Africa, as well as the available data on their use of
      reproductive health services. The aim is to provide guidance to health
      professionals on aspects of sexual and reproductive health in women with RHD. It
      reviews the diagnosis, management and counselling of women with RHD throughout
      their reproductive life. Additionally, this publication discusses potential ways
      of integrating obstetric and cardiovascular care at peripheral levels of the
      health systems, as a way of improving outcomes and reducing maternal mortality
      rates related to cardiovascular disease in Africa. Finally, the article proposes
      responses to fulfil the actual needs for better reproductive health services and
      improvement in care for women with RHD.

PMID- 30234227
TI  - Multichromatic TTF staining characterizes cartilage matrix in osteoarthritis and
      bone development.
AB  - Various histological staining methods have been explored to detect the joint
      lesions in osteoarthritis (OA), but these histological stains cannot
      comprehensively present the comparatively complex structures of articular
      cartilage in knee OA. In addition, no integrated histological staining method can
      be used to evaluate efficiently both the subzone region and matrix composition in
      cartilage containing tissues. Therefore, in this study, a novel multichromatic
      staining method termed TTF staining, using Toluidine Blue (T), Tartrazine (T) and
      Fast Green (F) sequential combined staining for histological analysis, has been
      exploited to characterize the changes of matrix components and contents in
      cartilage during OA and in the bone development. This specific TTF staining
      profile can be used to differentiate the major compartments of knee joint region,
      including the synovium, meniscus, multiple subzones of cartilage and subchondral
      bone. An anterior cruciate ligament transection induced OA model in rat has been
      established to profoundly present the alterations of glycosaminoglycans in
      cartilage degeneration by TTF staining profile. The changes of TTF staining
      profile in the chondrification and ossification centers of the postnatal rat knee
      joint indicate the developmental features of cartilage matrix during the growth
      of bone. In summary, we have developed an effective histological staining method
      that enables us to identify the subzones of cartilage in detail and to define the
      matrix features of bone development. Therefore, finally using this new TTF
      staining method may help us to exploit a histopathological grading system to
      assess cartilage lesions in clinical disease.

PMID- 30234228
TI  - [Nutritional diet therapy in the management of the patient with Chronic Kidney
      Disease in advanced phase to delay the beginning and reduce the frequency of
      dialysis. An option also in the pre-emptive transplant program].
AB  - The Italian nephrology has a long tradition and experience in the field of
      dietetic-nutritional therapy (DNT), which is an important component in the
      conservative management of the patient suffering from a chronic kidney disease,
      which precedes and integrates the pharmacological therapies. The objectives of
      DNT include the maintenance of an optimal nutritional status, the prevention and
      / or correction of signs, symptoms and complications of chronic renal failure
      and, possibly, the delay in starting of dialysis. The DNT includes modulation of
      protein intake, adequacy of caloric intake, control of sodium and potassium
      intake, and reduction of phosphorus intake. For all dietary-nutritional
      therapies, and in particular those aimed at the patient with chronic renal
      failure, the problem of patient adherence to the dietetic-nutritional scheme is a
      key element for the success and safety of the DNT and it can be favored by an
      interdisciplinary and multi-professional approach of information, education,
      dietary prescription and follow-up. This consensus document, which defines twenty
      (20) essential points of the nutritional approach to patients with advanced
      chronic renal failure, has been written, discussed and shared by the Italian
      nephrologists together with representatives of dietitians (ANDID) and patients
      (ANED).

PMID- 30234229
TI  - [PD in Italy: the 5th GSDP-SIN Census 2014].
AB  - OBJECTIVES: To know PD modalities and results in Italy. METHODS: The Census was
      carried out by means of an on-line questionnaire in ALL the 225 non-pediatric
      public centers which PERFORMED PD in 2014. The results were compared with those
      of previous Censuses (2005:Cs-05; 2008:Cs-08; 2010:Cs-10; 2012:Cs-12). RESULTS:
      Incidence. In 2014 PD was begun (first treatment for ESRD) by 1,652 pts (CAPD:
      57.2%) and HD by 4,442 pts (%PD-incidence= Cs-14: 27,1%; Cs-12: 23.4%; Cs-10:
      23.3%; Cs-08: 22.8%; Cs-05: 24.2%). For the first time Incremental PD does not
      increase (Cs-14: 27,5%; Cs-12: 28,8%; Cs-10: 22,8%; Cs-08: 18,3%; Cs-05: 11,9%).
      Prevalence. At 31/12/2014 there were 4,480 patients on PD (CAPD: 46.9%) (%PD
      prevalence= Cs-14: Cs-12: 17.1%; Cs-10: 16.6%; Cs-08: 16.7%; Cs-05:16.8%; p=NS),
      24.3% of whom were on assisted PD (family members: 83.6%; paid caregivers: 11.5%;
      nurses: 1.1%; NH: 2.8%). Out. In 2014 there was no change in the PD drop-out rate
      (32.0 ep/100yrs-pt) (death: 502; transplant: 329; switch to HD: 528 pts). The
      main reason for transferring to HD remained peritonitis (24.8%). Choice (9.3%)
      and impossibility to continue PD (15.2%) are increasing. Peritonitis. The
      peritonitis rate (953 episodes) was 0.224 ep/yrs-pt. The incidence of new cases
      of EPS in 2013-14 (39 cases=0.444 ep/100yrs-pt) is decreasing (2011-12= 0.505;
      2009-10= 0.529; 2004-08= 0.701 ep/100-yrs-pt). Other results. Compared to 2012,
      in 2014 the number of Centers using 3.86% for PET increased (41.3%) (Cs-12:
      30.8%; Cs-10: 15.6%; p <0.001), while the number carrying out home visits (59.6%)
      remained unchanged (56.3% in 2012, 59.4% in 2010). CONCLUSION: Cs-14 confirms the
      extensive use, stability and good results of PD in Italy. Incremental PD and
      assisted PD are unchanged, peritonitis are decreased and EPS remains a rare
      event. PET-3.86% is increasingly used.

PMID- 30234230
TI  - [Direct-acting antiviral agents, hepatitis C and dialysis: an update].
AB  - Hepatitis C virus infection is still common among patients with chronic kidney
      disease, particularly within Dialysis Units all over the world. Although the full
      extent of HCV transmission in dialysis units is unknown, outbreaks of HCV
      infection continue to occur all over the world. Evidence has been accumulated in
      the last decade suggesting that HCV plays consistent activity at hepatic and
      extra-hepatic level. A recent systematic review of the medical literature with a
      meta-analysis of clinical studies retrieved 15 longitudinal studies (n=2,299,134
      patients) ; we found a significant relationship between anti-HCV positive
      serologic status and higher frequency of CKD; the summary estimate for adjusted
      hazard risk with HCV across the surveys, 1.54 (95% CI, 1.26; 1.87) (P<0.0001).
      The advent of direct-acting antiviral agents has revolutionized the therapy of
      HCV, including patients with advanced chronic kidney disease. Two regimens based
      on DAAs have been recently approved for the antiviral therapy of HCV in patients
      with CKD stage 4/5: elbasvir/grazoprevir and glecaprevir/pibrentasvir. Such
      regimens have been provided with high efficacy and safety, according to the
      results given by C-SURFER and EXPEDITION-4, respectively. Sofosbuvir, a non
      structural 5B polymerase inhibitor, is the backbone of many anti-HCV drug
      regimens, and has significant renal excretion. As a result, the use of sofosbuvir
      is not recommended in patients with an eGFR <30 mL/min/1.73m2. In summary, recent
      studies have shown that several combinations of DAAs are currently available for
      CKD patients, including those with CKD stage 4/5. These drugs have reported high
      efficacy and satisfactory tolerability, regardless of HCV genotype or renal
      impairment. We need to improve the screening for HCV and the access to DAAs in
      patients with CKD stage 4/5.

PMID- 30234231
TI  - [Hyperphosphatemia in dialysis: which binder?]
AB  - Several studies have evidenced the association between high serum phosphorus
      concentrations and adverse events especially in patients on dialysis. Recent K
      DIGO guidelines suggest lowering elevated phosphate levels toward the normal
      range. This goal should be achieved by combining dietary counseling, optimizing
      dialysis procedures and prescribing phosphate binders. Despite the availability
      of several binders, the "ideal" phosphate binder that combines high efficacy, low
      pills burden, minimal side effects and low cost is still not available. In
      clinical practice it is crucial to reach a high patient's compliance to therapy.
      The pill burden is the most relevant factor contributing to low compliance. This
      is the case of phosphate binder therapy that represents almost 50% of total pills
      prescribed to patients on dialysis. It has been evidenced an association between
      pills of phosphate binder and poor control of phosphorus and PTH. In recent years
      sucroferric oxyhydroxide is available as a new phosphate binder. Its peculiarity
      is an high phosphate binding capability that requires prescription of low number
      of pills per day. This characteristic has been confirmed by several randomized
      controlled trials. These trials have also evidenced that sucroferric oxyhydroxide
      may cause some gastrointestinal side effects. There is an ongoing study to
      confirm in "the real world" the incidence of side effects reported by controlled
      trials.

PMID- 30234232
TI  - [Hyperkalemia treatment in chronic kidney disease patients: overview on new K
      binders and possible therapeutic approaches].
AB  - Hyperkalaemia is a common complication in patients with nondialysis Chronic
      Kidney Disease (CKD). It is associated with weakness, paralysis, arrhythmias and
      increased mortality. Higher serum potassium levels refractory to treatment is one
      of the most frequent reasons to initiate immediately renal replacement treatment
      in advanced stages of CKD. Hyperkalaemia is also indirectly associated with the
      progression of CKD; in fact higher serum potassium levels may lead to withdrawal
      of renin-angiotensin-system inhibiting drugs that currently represent the most
      effective tools to postpone ESRD. It is therefore essential to identify patients
      at higher risk of increase of serum K and to implement therapeutic interventions
      aimed at preventing and treating hyperkalaemia, such as diet modifications and
      greater use of diuretics and cation exchange resins. Sodium and calcium
      polystyrenesulfonate (SPS) are the resins currently available in Italy. However,
      few studies showed that SPS is efficacious to reduce serum K and is associated
      with increased risk of severe adverse effects. Patiromer and ZS-9 represent a
      significant pharmacological progress in the treatment of hyperkalemia. Indeed,
      recent studies showed that these novel resins are efficient to reduce serum
      levels of K with minor occurrence of side effects than polystyrensulfonates.
      Furthermore, Patiromer, sodium free agent, might have a further advantage in CKD
      patients, reducing the salt intake in these patients. In addition, ZS-9, being
      fast-acting drug, might be used also in the treatment of acute hyperkalaemia.

PMID- 30234233
TI  - [A case of Anderson-Fabry disease: a multidisciplinary approach for diagnosis and
      follow up].
AB  - Fabry disease (also known as Anderson-Fabry disease, angiocheratoma corporis
      diffusum, diffuse angiocheratoma) is a rare tesaurismosis linked to the
      deficiency of the lysosomal enzyme alpha-galactosidase A, required for the
      physiological catabolism of glycosphingolipids. The related clinical signs show a
      multisystemic feature and define a degenerative and disabling pathology, whose
      approach requires a close multidisciplinary specialist collaboration. Currently,
      the renewed interest in the disease is aimed at the need to provide an early
      diagnosis, in order to early begin the enzyme replacement therapy and to slow
      down or avoid the establishment of irreparable organ damage. For this reason, the
      diagnostic suspicion becomes crucial and arises from the careful observation and
      research of the symptoms, together with the anamnesis and the overall clinical
      evaluation of the patient.

PMID- 30234234
TI  - [Encrusted Pyelitis during a case of Thrombotic Thrombocytopenic Purpura].
AB  - Encrusted pyelitis is a chronic urinary tract infection associated with mucosal
      encrustation induced by urea splitting bacteria. More than 40 bacteria have been
      implicated but the most frequent is Corynebacterium group D2. Predisposing
      factors are debilitating chronic diseases and preexisting urological procedures.
      Immunosoppression is an important cofactor. For these reasons the disease is
      almost always nosocomially acquired and renal transplant recipients are at
      particular risk. The symptoms are not specific and long lasting: dysuria, flank
      pain and gross haematuria are the most frequent; fever is present in two-thirds.
      The demonstration of urine splitting bacteria in constantly alkaline urines and
      radiological evidence of extensive calcification of pelvicalyceal system, ureter
      and bladder at US or CT scan in a clinical context of predisposing factors are
      the mainstay of diagnosis. Treatment is based on adapted antibiotic therapy,
      acidification of urine and excision of plaques of calcified encrustation. The
      prognosis relies on timing of diagnosis; delay can be detrimental and result in
      patient's death and graft loss. We describe a unique case of 69-year-old man with
      two contemporary diseases: autoimmune thrombotic thrombocytopenic purpura and
      encrusted pyelitis with a fatal evolution.

PMID- 30234235
TI  - [A case of severe metformin-associated lactic acidosis treated with CVVHDF and
      regional anticoagulation with sodium citrate].
AB  - : Metformin is an antidiabetic drug; used to treat type II diabetes mellitus,
      metformin associated lactic acidosis has an incidence of 2-9 cases / 100,000
      patients / year with high mortality (30%). We have had the case of a 75-year-old
      woman with metabolic acidosis as a result of metformin assumption, treated by
      renal replacement therapy (CRRT) with continuous veno-venous hemodiafiltration
      (CVVHDF). RESULTS: after a short treatment period there was a reduction in
      Lactates (from 16.8 mmol/L to 12.6 mmol/L) and a progressive improvement of
      acidosis. In 72 hours the recovery of diuresis and subsequent suspension of CRRT
      was achieved. CONCLUSION: CRRT, in addition to ensuring support for renal failure
      and volume correction, allowed a rapid recovery from metformin-associated lactic
      acidosis.

PMID- 30234236
TI  - [Challenges and results of the PIRP project (Prevenzione della Insufficienza
      Renale Progressiva) of the Emilia-Romagna Region].
AB  - The PIRP project was conceived in 2004; with the aim to face the increased
      prevalence of chronic kidney disease (CKD) associated with the aging and
      increased survival of the population. The first phase of the project consisted of
      training primary care physicians to identify people at risk of CKD and to
      implement intervention strategies that proved to be effective in preventing CKD
      it or delaying its progression once it is established. In the second phase of the
      project, dedicated ambulatories were opened in the nephrology units of Emilia
      Romagna hospitals to provide an in-depth assessment and personalized care to CKD
      patients, following them up until renal failure or death or referring them back
      to general practitioners, according to the study protocol. A web-based registry
      was implemented to collect demographic and clinical data on PIRP patients. As of
      30 June 2018, the registry included 26.211 CKD patients, with a median follow-up
      of 24.5 months. Over the 14 years of the PIRP the mean age of incident patients
      increased from 71.0 years to 74.2 years and the mean eGFR increased from 30.56 to
      36.52 mL/min/1.73 m 2, proving that the project was successful in recruiting
      older patients with a better renal function. At 5 years, the percentage of
      patients still active in the project was =45%.The implementation of the project
      has seen a reduction in the number of patients arriving every year to the
      dialysis treatment in E-R (about 100 units less from 2006 to 2016). The PIRP
      cohort is the largest in Italy and in Europe, which makes it ideal for research
      based on international comparisons and as a model for national registries.

PMID- 30234237
TI  - [Metabolic effects of Cholecalciferol supplementation in kidney stone formers
      with vitamin D deficiency].
AB  - INTRODUCTION: In this paper we investigated whether cholecalciferol
      supplementation, prescribed to treat vitamin D deficiency in patients with
      nephrolithiasis, increased the risk of stone recurrence. METHODS: Calcium
      excretion and urine supersaturation with calcium oxalate (betaCaOx) and brushite
      (betabsh) were evaluated in 33 kidney stone formers (aged 56+/-17; 12 males),
      both before and after therapy with cholecalciferol, prescribed as oral bolus of
      100.000-200.000 UI, followed by maintenance doses, repeated every week (5.000
      10.000 UI) or month (25.000-50.000 UI). During the study, patients followed a
      dietary regimen which included a daily calcium intake of about 800-1000 mg.
      RESULTS: Urinary nitrogen, sodium and ash-acid excretion did not significantly
      change during the study. After cholecalciferol supplementation, the main results
      were as follows: both serum calcium and phosphate did not vary significantly;
      25(OH)VitD3 increased from 11,8+/-5,5 to 40,2+/-12,2 ng/mL (p<0,01); 1,25(OH) 2
      VitD3 increased from 41,6+/-17,6 to 54,0+/-16,0 pg/mL (p<0,01); PTH decreased
      from 75,0+/-27,2 to 56,7+/-21,1 pg/mL (p<0,01); daily urinary calcium increased
      from 2,7+/-1,5 to 3,6+/-1,6 mg/Kg b.w. (p<0,01), whereas fasting urinary calcium
      did not change significantly. After therapy, betabsh increased from 0,9+/-0,7 to
      1,3+/-1,3 (p=0,02) and betaCaOx did not vary significantly. Before
      cholecalciferol supplementation, 6/33 patients (18.2%) were hypercalciuric,
      whereas 13/33 patients (39,4%) showed hypercalciuria after supplementation
      (pX2=0,03). CONCLUSIONS: Cholecalciferol supplementation for vitamin D deficiency
      may increase both urinary calcium and urine supersaturation in stone formers. If
      vitamin D supplements are needed in these patients, a careful monitoring of urine
      metabolic profile is warranted, in order to customize the metaphylaxis
      accordingly (hydration, potassium citrate, thiazides).

PMID- 30234238
TI  - [Microbiological quality of hemodialysis water: what are the risk factors?]
AB  - BACKGROUND: A dialyzed patient weekly gets in touch with a large amount of water
      (on average 350 liters) through the dialysis bath. It is therefore essential that
      this solution would have a high quality and purity. The aim of our study was to
      monitor the microbiological quality of the hemodialysis water in order to
      identify possible factors that could affect it. METHODS: We conducted a cross
      sectional study from January 2015 to October 2017 collecting the dialysis water
      in AOU Careggi. Samples were aseptically collected by specialized technicians and
      then transported under ice at 4 degrees  C to the Laboratory of Biological
      Hazards of USL Toscana Centro for laboratory analyses. RESULTS: 126 water samples
      were collected. Coliforms, E. coli, Staphylococcus aureus, enterococci were not
      detected. Pseudomonas aeruginosa was found in only one sample. Both for CFU at 37
      degrees  C and at 22 degrees  C, the type of device represented the only
      statistically significant risk factor (OR 15.21 and OR 10.25 respectively): SDS
      devices had a significantly higher risk of being positive for CFU at 37 degrees 
      C and 22 degrees  C. CONCLUSIONS: As our study demonstrated, the system producing
      dialysis water must be constantly monitored, especially in cases of SDS devices
      which may be subjected more frequently to a higher contamination, due to their
      discontinuous use.

PMID- 30234239
TI  - [An alternative proposal for managing morphological examination of urinary
      sediment and increasing its appropriateness].
AB  - BACKGROUND: The morphological examination of urinary sediment (MEUS) is
      traditionally associated with urinalysis (UA), with workload implications and the
      need for automation of its execution. METHODS: Considering MEUS as a test
      requiring specialized knowhow and skill for its execution, since 2005 in our
      laboratory it is performed for inpatients only upon specific request. Eleven
      years after, we have analyzed the long-term impact of this approach on the
      provided service. We evaluated results in the 2009-2016 period, in which our
      hospital did not undergo any change both in the number of beds and in the
      clinical case-mix. RESULTS: From 2009 to 2013 an average of 2264 MEUS and 10,204
      UA per year were ordered, respectively, with an average ratio of 22.2%. Since
      2014, a change on computerized order entry involving MEUS caused a further
      decrease of its requests (in average, 923 per year), which was not associated to
      a decrease in UA (in average, 9810 per year) (in average, MEUS/UA 9.4%). MEUS
      requests came mainly from Paediatrics (47.8%), Nephrology (20.9%) and
      Rheumatology (18.3%) wards. By filling a satisfaction survey, clinical wards
      evaluated the provided service as satisfactory, while highlighting some critical
      issues, mainly referred to preanalytical phase. CONCLUSIONS: The alternative
      proposal for managing MEUS presented in this paper markedly reduces the number of
      requests and increases their appropriateness. This is achieved without any
      negative impact on patient care.

PMID- 30234240
TI  - [Inapparent charges for the assistance to nephropathic patient on dialysis].
AB  - The increasing technological effectiveness has undoubtedly produced an
      improvement in clinical parameters of dialysis patients, but this satisfactory
      therapeutic result did not follow an adequate improvement in mortality or in the
      perception of quality of life as per patients. Furthermore, dialysis treatment is
      often associated with "inapparent charges" that reduce the perception of well
      being, independently of clinical changes. Thirty years ago, we carried out a
      national survey on inapparent charges, which represent frustrating aspects that
      negatively affect patients' perception of their quality of life. Thirty years
      later, it seemed important for us to repeat the survey to understand if Italian
      legislative remodeling have introduced changes in procedures and social aspects
      of dialysis, as preservation of quality of life is an important aspect of the
      replacement treatment.

PMID- 30234241
TI  - Meeting the healthcare needs of people experiencing homelessness.
AB  - People experiencing homelessness have unique healthcare and health promotion
      needs. This article provides nurses with information on the healthcare challenges
      that commonly affect people who are experiencing homelessness, and outlines
      various effective nurse-led interventions that can be implemented. It provides
      examples of nurse-led health promotion projects, which demonstrate how a
      collaborative approach can improve the healthcare experiences of this patient
      group. This article also examines the issue of homelessness and mental capacity,
      as well as explaining the role of physical health outreach services in caring for
      people experiencing homelessness.

PMID- 30234242
TI  - Local Skin Cooling as an Aid to the Management of Patients with Breast Cancer
      Related Lymphedema and Fibrosis of the Arm or Breast.
AB  - Based on preliminary observations that topical cooling appeared to soften
      lymphedematous and fibrotic tissue, our goal was to systematically and
      quantitatively evaluate this effect. For this purpose, topical cooling was used
      as part of treatment of lymphedematous and fibrotic skin of women with breast
      cancer related lymphedema (BCRL) and localized fibrosis. Skin tissue hardness was
      assessed via the force required to indent skin to 4 mm (F4.0) and 1.3 mm (F1.3)
      and skin water was assessed by measurements of tissue dielectric constant (TDC).
      Measurements were done before cooling, after cooling, and after a single
      treatment session in 20 women with arm involvement and in 12 women with breast
      involvement. Pre-cooled arm and breast skin temperatures (mean +/- SD) of 32.4 +/
      1.4 degrees C and 33.8 +/- 1.0 degrees C were reduced to 23.7 +/- 2.0 degrees C
      and 24.7 +/- 1.6 degrees C respectively via application of cold washcloths.
      Cooling was associated with a significant (p<0.001) decrease in F4.0 and F1.3 at
      arm and breast sites. At arm sites, force reductions ranged from 24% to 28%
      depending on indentation depth. Although the precise mechanism linking cooling to
      softening is as yet not fully understood, the fact that tissue is softened
      carries with it many potential benefits to patient and therapist. The near
      immediate tissue softening is associated with less pressure on underlying nerve
      endings and less input to sensory nerves thereby interrupting the pain cycle
      resulting in rapid pain relief. The rapidly softened tissue and decreased
      perception of pain offers the patient hope and encouragement in their therapeutic
      journey to reclaiming functional use of their affected body. Further, because
      softer tissue becomes more pliable, myofascial lengthening, scar tissue
      releasing, and other aspects of treatment are easier to perform thereby reducing
      treatment time and effort while achieving improved functional mobility.

PMID- 30234243
TI  - Neonatal Lymphedema from Thoracic Duct Obstruction Complicating Percutaneous
      Intravenous Central Catheterization.
AB  - Percutaneous intravenous central catheter (PICC) complications are not common and
      generalized edema and anasarca in neonates as a complication of PICC malposition
      is even rarer. Documentation of the pathomechanisms of lymphedema in cases of
      severe anasarca in neonates is not often done. Here we document thoracic duct
      obstruction as the cause of lymphedema in a neonate with severe nonpitting
      generalized edema. Most PICC procedures should ideally be guided by point-of-care
      bedside ultrasound (US), and this precaution may prevent malposition of PICC
      lines although it will not detect subsequent migration or extravasation.

PMID- 30234244
TI  - Transdifferentiated Monocytes: a Novel Source of Lymphatic Endothelial-like
      Cells.
AB  - Although monocytes have previously been demonstrated to contribute to lymphatic
      vessel formation in vivo, monocyte transdifferentiation into lymphatic
      endothelial cells and the specific conditions required remain unclear. In this
      study, monocyte cultures isolated from human peripheral blood were stimulated to
      transdifferentiate into lymphatic endothelial cells under specific in vitro
      induction conditions. These results demonstrate primary isolates of CD14 (+)
      monocytes express low levels of lymphatic endothelial cell specific markers or
      pan-endothelial markers under routine culture conditions. Using fibronectin (FN)
      coated flasks and EGM-2 supplemented culture medium, monocytes were induced to
      express lymphatic endothelial markers Prox-1, VEGFR-3, LYVE-1, Podoplanin, and
      pan-endothelial markers vWF, CD144, and VEGFR-2. Furthermore, using the FN/EGM
      2/lipopolysaccharide (LPS) culture conditions, monocytes displayed dramatically
      increased expressions of Prox-1, VEGFR-3, Podoplanin, LYVE-1 and vWF, while the
      expression of CD144 and VEGFR-2 sharply decreased. In addition, VEGF-C secretion
      by monocytes exposed to fibronectin coated plates with EGM-2 medium with FN/EGM
      2/LPS in vitro was significantly increased over levels seen in routine culture
      conditions. These findings demonstrate that monocytes can be induced to undergo
      transdifferentiation becoming more lymphatic endothelial-like cells and increase
      their VEGF-C production in an FN/EGM-2/LPS environment.

PMID- 30234245
TI  - Is Ultrasonography a Useful Method to Evaluate the Effectiveness of Complex
      Decongestive Therapy in Breast Cancer-related Lymphedema?
AB  - In recent years the use of ultrasonography has become widespread in the field of
      lymphedema especially as an aid for diagnosis. The aim of this study was to
      evaluate whether ultrasonography is a useful method to assess the efficacy of
      complex decongestive therapy (CDT). Circumferences and ultrasonographic
      evaluations (cutis and subcutis thickness) were performed at 10 cm proximal and
      distal to the elbow and limb volume (upper and forearm) was calculated from
      circumferences at six anatomic landmarks by using truncated cone formula.
      Measurements were recorded before and after CDT on both sides. A total of twenty
      six women (mean age 51.3 +/- 10.8) with the diagnosis of breast cancer-related
      lymphedema (BCRL) were enrolled in the study. Significant reduction in the
      subcutis thickness was observed on the affected side after the treatment period,
      and the percentage change in subcutis thickness was correlated with the
      percentage change in edema. This study also demonstrated that the soft tissue
      thickness was higher in the affected arm and ultrasonographic findings were
      consistent with the other measurement methods (circumferences and limb volumes).
      Considering that ultrasound imaging is patient-friendly, non-invasive, and cost
      effective, we recommend its more widespread use for evaluating treatment efficacy
      in BCRL.

PMID- 30234247
TI  - Lymphangioleiomyomatosis and Gorham-Stout disease: Primary or secondary disorders
      of the lymphatic system?
AB  - Lymphangioleimyomatosis and Gorham- Stout disease, rare disorders which share
      features of proliferating lymphatic vessels, predominantly in the lung in the
      former and bone in the latter, commonly manifest as progressive lung disease
      often associated with life-threatening complications of chylous reflux from
      central lymphatic obstruction/ leakage. This Lymphspiration-Editorial proposes
      that, rather than a secondary complication, lymphatic obstruction/ dysfunction is
      a much earlier or even the primary event in the pathogenesis of both disorders
      and that lymphostasis drives the cellular proliferative response in both lung and
      bone and even distant sites.

PMID- 30234246
TI  - Lymphatic Architecture of Suncus Murinus (House Musk Shrew) Palatum.
AB  - The architecture of craniocervical lymphatic vessels in rodents has been examined
      previously. In the present study, we evaluated the distribution of collecting
      lymphatic vessels in the palate of Suncus, which is known to retain the prototype
      of placental mammals and is more similar to humans in terms of jaw bone
      morphology when compared with rodents. Three-dimensional reconstructed images of
      the Suncus palatum revealed that the collecting lymphatic vessels were connected
      to each other via smaller branches, and ran in an antero-posterior direction in
      the periosteum. The vessels entered the pair of posterior palatine foramina
      located near the fourth premolar or the first molar bilaterally, coursed through
      the posterior palatine canals, and reached the pterygopalatine fossa positioned
      posteriorly in the palate. The collecting lymphatic vessels changed directions
      from medial to superior to lateral while wrapping around arteries during their
      course, perhaps to enable the smooth transition from the palate to the deep
      cervical node. Inefficient lymphatic flow in humans is attributed to the superior
      location of the pterygopalatine fossa in the palate when compared with its
      location in the Suncus.

PMID- 30234248
TI  - The volume of postoperative drainage fluid as a potential early predictor of
      lymphedema after lymph node excision for metastatic melanoma.
AB  - Lymphedema (LE) following lymph node dissection is a major problem for cancer
      patients, and radiation therapy, extended surgery, groin dissection, obesity, and
      older age are well-established risk factors of LE. We studied whether these risk
      factors are further associated with high volumes of postoperative drainage fluid
      after complete lymph node dissection (CLND) for melanoma metastases. Moreover, we
      examined whether a high amount of drainage fluid after sentinel lymph node biopsy
      (SLNB) can predict a high amount of drainage fluid after subsequent CLND. Using
      descriptive statistics and regression analyses, we analyzed the cumulative
      volumes of postoperative drainage fluid for 836 melanoma patients with lymph node
      excision in the axilla or groin. In multiple regression analyses, the well
      established risk factors of LE, i.e., increased body mass index, older age, and
      ilioinguinal versus inguinal versus axillary dissection predicted a high drainage
      volume after CLND. Of note, a high drainage fluid volume after SLNB also
      predicted a high drainage volume after subsequent CLND. In patients with groin
      dissections, who are particularly susceptible to swelling, extended iliac
      dissection, age above 60, and a cumulative drainage volume of more than 100 ml in
      the preceding SLNB were predictors of the cumulative drainage volume. We find
      that common risk factors predict the volume of postoperative drainage fluid after
      CLND and postoperative LE. Further, high postoperative drainage volume may
      therefore function as a potential early predictor of LE following CLND.

PMID- 30234249
TI  - Long-term follow-up of collateral pathways established after lymphadenectomy in
      rats.
AB  - A collateral pathway established after lymphadenectomy could play an important
      role in long-term lymphedema treatment. The present study investigated
      alterations of lymph dynamics 1 year after lymphadenectomy using indocyanine
      green fluorescent lymphography to determine if a collateral pathway may be used
      for long-term lymphedema treatment. Wistar rats were anaesthetized and lymph
      nodes were excised at the inguinal and popliteal fossae. The treated hind limb
      was evaluated by fluorescent lymphography between 10 weeks and 6 months and
      between 6 months and 1 year postoperatively. Fluorescent lymphography
      demonstrated a lymphatic pathway to the ipsilateral axillary fossa in all rats 1
      year after lymphadenectomy. Some capillary branches in the paths leading to the
      ipsilateral axillary fossa were dilated and tortuous. In addition, areas in which
      a fluorescent signal was not visible were increased in the thigh. In conclusion,
      the collateral pathway did not appear to be only for temporary use to compensate
      for drainage from the edematous limb but appears more stable as a component of a
      compensating lymphatic system. These new dilated vessels, although functional at
      this point, may still be susceptible to disturbance by further alteration to the
      lymph vessels.

PMID- 30234250
TI  - Multi-modal imaging features and lympho-venous shunt for vaginal chylous fistula
      in lymphangioleiomyomatosis: Case report and review.
AB  - Vaginal chylous fistula is a very rare lymphatic disorder and
      lymphangioleiomyomatosis (LAM) is also a rare multisystemic disease. LAM with the
      development of a vaginal chylous fistula has rarely been reported. Here we report
      a case of vaginal chylous fistula accompanied with LAM. A 61-year-old woman
      occasionally experiencing milky vaginal discharge for the last 3 months underwent
      CT lymphangiography (CTL) after direct lymphangiography (DLG) and
      lymphoscintigraphy. DLG showed lymph flowing backwards toward the pelvic cavity.
      CTL revealed abnormal distribution of contrast agent in the pelvic cavity,
      including uterus, vagina, perineum, bladder, and muscles in the bilateral pelvis.
      Multiple small thinwalled cystic lesions were present in both lungs.
      Lymphoscintigraphy demonstrated lymphangiectasia in the pelvic cavity bilaterally
      with radionuclide tracer flowing back abnormally into the pelvic walls. The
      vaginal exudate was positive for chyle. According to LAM guidelines, the patient
      was diagnosed with LAM. This case presents multimodal images of a rare case of
      vaginal chylous fistula accompanied with LAM and highlights the value of CT
      lymphangiography after DLG in establishing the diagnosis and providing important
      guidance for sequential therapy.

PMID- 30234251
TI  - A new combined operative technique using crossed inguinal lymphatic rescue for
      pediatric patients with mixed lymphatic and venous malformations.
AB  - Truncular venous malformations and acquired functional or anatomical venous
      occlusions (or sub-occlusions) can be the cause of secondary lymphedema and even
      the cause of primary lymphedema when they are associated with lymphatic
      malformations (lymphangiodysplasia - LAD I, lymphadenodysplasia - LAD II, or a
      combination of both) in pediatric patients. This understanding recognizes the
      shared and successive embryogenesis of both systems. These conditions can exhibit
      hypertension in the venous pedicles intended for lymph-venous anastomosis, and
      this finding would be a formal contraindication to the procedure. However, this
      hypertension is a rarely considered condition and is not commonly identified. As
      a technique to solve this problem, we have combined Nielubowicz, Olszewski,
      Campisi, and Palma's proposals and created a lymph-venous anastomosis from the
      side with lymphedema and venous hypertension (lymphatic donor and venous
      recipient) with an internal suprapubic saphenous venous bridge (from the normal
      side to the lymphedematous side with venous hypertension) to enable a crossed
      inguinal lymphatic/venous rescue. We believe this newly synthesized approach will
      allow better clinical care of pediatric patients with complex and combined
      lymphatic-venous malformations and is worthy of further investigation.

PMID- 30234252
TI  - Can obstructive intralymphatic granulomas be the cause of cheilitis
      granulomatosa?
AB  - Cheilitis granulomatosa (ChG), also known as Miescher's cheilitis, is an
      uncommon, immunologically mediated nonnecrotizing granulomatous inflammatory
      disease characterized by recurrent, painless swelling of the lips. The aim of the
      study was a pathomorphological and immunohistochemical assessment of cases
      clinically classified as ChG to investigate potential pathological mechanisms of
      ChG symptoms and to verify the hypothesis of intravascular granulomas as a cause
      of lymphatic vessel obstruction and localized edema in ChG. We report 6 patients
      with ChG who clinically presented localized edema of the lips. Lip biopsy with
      pathomorphological and immunohistochemical examination was performed in all
      cases. We found discrete, non-necrotizing granulomas which were adjacent to
      numerous blood and lymphatic vessels. The lumen of lymphatic channels was dilated
      and was either empty or contained lymph and few macrophages or was completely
      occluded by nearby granulomas. All patients demonstrated a characteristic pattern
      of lymphangiectasia and perivascular lymphatic aggregates with evidence of non
      necrotizing granulomas. None manifested intralymphatic granulomas. These results
      do not support the view that lymphatic vessel obstruction is caused by
      intravascular histiocytic granulomas described as the main part in the etiology
      of lymphatic edema in ChG. However, perivascular granulomas and dilation of
      lymphatic vessels confirm presence of inflammatory lymphostasis in all studied
      cases of ChG.

PMID- 30234253
TI  - Successful diagnosis of lymphangioleiomyomatosis with transbronchial lung
      cryobiopsy.
AB  - A 47-year old female was evaluated in our clinic for an incidental discovery of
      diffuse cystic lung disease on high-resolution computed tomography (CT) scan of
      the chest. There was no personal or family history of tuberous sclerosis complex
      (TSC), sicca symptoms, pneumothorax, or skin or renal tumors. Review of her chest
      CT scan showed bilateral, round, uniform, thin-walled cysts present in a diffuse
      distribution characteristic of lymphangioleiomyomatosis (LAM). CT scan of the
      abdomen and pelvis did not reveal angiomyolipomas, lymphangioleiomyomas, abnormal
      lymphadenopathy, or chylous fluid collections. Serum vascular endothelial growth
      factor-D was non-diagnostic. In order to achieve diagnostic confirmation, the
      patient underwent transbronchial cryobiopsy of the lung, revealing changes
      consistent with LAM. Our case highlights the utility of transbronchial lung
      cryobiopsy in the evaluation of patients with suspected LAM and suggests that
      further investigation of this diagnostic technique is warranted in patients
      presenting with diffuse cystic lung disease.

PMID- 30234254
TI  - ?

PMID- 30234255
TI  - Nature and nurture: Not a case of either/or.

PMID- 30234256
TI  - ?

PMID- 30234257
TI  - ?

PMID- 30234258
TI  - ?

PMID- 30234259
TI  - ?

PMID- 30234260
TI  - ?

PMID- 30234261
TI  - ?

PMID- 30234262
TI  - Children and adolescents need protection against energy drinks.

PMID- 30234263
TI  - ?

PMID- 30234264
TI  - Balanced or imbalanced samples?

PMID- 30234265
TI  - ?

PMID- 30234266
TI  - ?
AB  - BACKGROUND: All Norwegian hospitals must submit data to the Norwegian
      Surveillance System for Antibiotic Consumption and Healthcare-Associated
      Infections (NOIS) regarding surgical site infections following coronary artery
      bypass graft, caesarean section, hip arthroplasty, cholecystectomy and colonic
      surgery. The purpose of our study was to identify the proportion of patients
      undergoing surgery in 2016 who developed a surgical site infection, and the
      consequences in the form of prolonged postoperative hospitalisation, readmission
      or revision surgery. MATERIAL AND METHOD: All patients who underwent one of the
      five surgical procedures registered in NOIS in 2016 were included and followed up
      for 30 days after the surgery. The criteria set out by the European Centre for
      Disease Prevention and Control were used to define infections. RESULTS: From
      among the 31 401 patients included, a total of 1 225 surgical site infections
      were recorded. The incidence was highest following colonic surgery (10.9 %) and
      lowest following total hip arthroplasty (1.8 %). Median postoperative length of
      hospitalisation was three days for those with no infection, and six days for the
      544 patients with a deep infection or an infection in an organ or cavity. The
      infections resulted in the need for revision surgery in 308 patients and
      readmission for 323 patients. INTERPRETATION: A total of 3.9 % of patients
      registered with a surgical procedure included in NOIS developed a surgical site
      infection. Consequences such as increased hospitalisation time, and more
      readmissions as well as revision procedures serve to highlight the importance of
      preventing such infections.

PMID- 30234267
TI  - ?

PMID- 30234268
TI  - ?

PMID- 30234269
TI  - Frostbite in the Norwegian Armed Forces.
AB  - BAKGRUNN: Det finnes lite forskning pa forekomst av frostskader, bade sivilt og
      militaert. Prognosen og tidsforlopet ved slike skader har ikke tidligere vaert
      undersokt i storre kohorter. MATERIALE OG METODE: Deltagerne var personer
      registrert i Forsvarets helseregister med kulde- og frostskade i tidsrommet
      1.1.2010-31.12.2014. Data om diagnostikk, forlop og behandling ble innhentet fra
      i alt 460 personer ved hjelp av et sporreskjema. Svarprosenten pa undersokelsen
      var 66. RESULTATER: 397 av 460 personer (86,3 %) som var registrert med
      frostskade i Forsvarets helseregister bekreftet at de hadde hatt en kulde- og
      frostskade. 123 av 397 personene som svarte (30,1 %) anga at de hadde hatt
      blemmer, noe som gir mistanke om at de hadde padratt seg annengrads frostskade.
      225 av 397 (56,7 %) anga at de hadde hatt frostskade, men ikke blemmer. De aller
      fleste fikk frostskaden under feltovelse/vinterovelse (81,1 %), og 2/3 av de som
      padro seg skader var vernepliktige. Langt de fleste hadde skader pa fingre/hender
      eller taer/fotter (96,0 %). To av tre (69,8 %) hadde fortsatt plager fra sin
      frostskade mer enn to ar etter skadetidspunktet. FORTOLKNING: Mange i militaeret
      padrar seg frostskader under tjenestegjoring. En femdel anga kroniske helseplager
      som pavirker arbeidsevnen. Kunnskap om forekomsten av frostskader hos militaert
      mannskap er viktig for Forsvarets videre skadeforebyggende arbeid.

PMID- 30234270
TI  - Risk factors for frontotemporal dementia.
AB  - BAKGRUNN: Risikofaktorer for frontotemporal demens er lite kartlagt. Formalet med
      denne artikkelen var a gi en oppdatert oversikt over modifiserbare risikofaktorer
      for frontotemporal demens og vurdere kunnskapsgrunnlaget for kliniske
      anbefalinger for a redusere risiko for sykdommen. KUNNSKAPSGRUNNLAG: Det ble
      utfort sok i basene PsychInfo, Embase, PubMed og Cochrane i perioden mai 2016
      april 2017. Soket ga totalt 137 artikler. 101 artikler ble ekskludert fordi de
      kun omhandlet genetiske aspekter ved frontotemporal demens og ikke modifiserbare
      risikofaktorer. Etter a ha lest 36 artikler i fulltekst inkluderte vi 12 artikler
      som enten var oversiktsartikler eller originalstudier. RESULTATER: Enkelte
      studier viste sammenheng mellom modifiserbare risikofaktorer og utvikling av
      frontotemporal demens. I en studie fant man at diabetes ga okt risiko. Tre
      studier viste at hodetraume kan gi okt risiko for frontotemporal demens og at
      forekomsten av traumatisk hodeskade var signifikant hoyere hos pasienter med
      frontotemporal demens enn andre former for demens. Autoimmun sykdom kan vaere
      forbundet med okt risiko for primaer progressiv afasi, en undergruppe av
      frontotemporal demens. FORTOLKNING: Litteraturen indikerte sammenheng mellom
      diabetes, hodetraume, autoimmun sykdom og frontotemporal demens. Det finnes per i
      dag ikke tilstrekkelig kunnskap for a fremme anbefalinger om livsstilsendringer
      for a forebygge frontotemporal demens pa befolkningsniva.

PMID- 30234271
TI  - ?

PMID- 30234272
TI  - [Implications of choice of products and impression technique on the thickness of
      the dento-prosthetic interface of the CAD-CAM crowns].
AB  - The purpose of this study is to find out what type of impression material is able
      to achieve a CAD-CAM (Procera) crown with minimal thickness at the dental
      prosthetic interface, taking into account the effect of the oversize replica and
      dimensional variations of the impression materials over time. The accuracy of the
      marginal adaptation will therefore depend on the oversize replica of clinical
      preparation controlled by the constant K. Three different types of impression
      materials: medium viscosity polyether (Impregum 3M-ESPE, Germany), silicones
      polyvinyl siloxane A (Putty + Very Light) and (Heavy + Light) (Express 3M-ESPE,
      Germany), were used for making impressions of fifteen initial prototype maxillary
      teeth made of nickel chrome. The cast of the impressions were poured with plaster
      type IV (Zhermack, Italy), on which thirty Procera crowns were fabricated. The
      thickness of the dental-prosthetic interface was then studied at three levels: 0,
      1 and 2 mm. The results show that the impression material has a statistically
      significant impact on the thickness of the dental-prosthetic interface at all
      three levels. The most compressive impression technique, Putty + Very Light gave
      the best results at the three levels pre-cited. The results analyzed under
      optical microscopy show a statistically significant difference between the three
      impression material products (p-value < 0.05). The calibration constant K,
      according to each clinical situation, can therefore lead to optimal dental
      prosthetic inter-face.

PMID- 30234273
TI  - [Prosthodontic care of orofacial clefts in adulthood: About a clinical case].
AB  - This paper relates, through a clinical case, the different steps of the
      prosthodontic rehabilitation of a palate-pharyngeal cleft, sequelae to surgery,
      by performing a Suersen's Velar obturator since the soft Palate is divided but
      toned. A functional reeducation in conjunction with a prosthodontic care improves
      the quality of life's patients and help for their resocialization. This
      therapeutic is non-invasive, quick, efficient and evolutive method.

PMID- 30234274
TI  - An analysis of treatment outcome in traumatised anterior teeth with delayed
      presentation.
AB  - Introduction: This study was designed to analyse the treatment outcome of
      traumatized anterior teeth with delayed presentation among adult patients.
      Method: A longitudinal study carried out among adult patients with traumatized
      anterior teeth. Data was obtained by means of a pre-tested questionnaire
      consisting of history taking, clinical examination and record of treatment. Data
      collected was analysed using the Statistical Package for Social Science 21.0.
      Results: Out of 163 patients who sought treatment for traumatized anterior teeth,
      102 presented a month or more after the traumatic incident giving a prevalence
      rate of 62.3% for delayed presentation. The main reason for seeking treatment was
      disfigured teeth. More than half (57.8%) of the participants presented with one
      or more complications. Evaluation revealed that 3 (2.7%) of the participants had
      failed restoration at 1-month recall and this was statistically significant.
      Conclusion: Delayed treatment has an implication on the type, complexity and cost
      of treatment. Evaluation after treatment for traumatized anterior teeth has to be
      done for a minimum of 3 months to ascertain optimal result. Oral health education
      should focus on the need to visit a dentist immediately after a traumatic episode
      with or without loss of dental hard tissue.

PMID- 30234275
TI  - [Oral Health attitude and Practices among children in boys' orphanage of Rabat,
      Morocco].
AB  - Introduction: Orphanages are a high-risk group of oral health diseases. The aim
      of this study was to evaluate oral hygiene attitudes among orphans living in Al
      Akkari orphanage in Rabat, Morocco. Materials and Methods: cross sectional study
      was conducted among 165 orphans aged between 6 and 15 years-old at the orphanage
      Al Akkari in Rabat, between December 2012 and February 2013. The information
      collect was realized by direct questioning of all the residents. The questions
      were asked by a dentist and concerned the attitudes of the residents towards
      principles of oral hygiene, the possession of toothbrush and dentifrice, tooth
      brushing frequency and methods and the existence or not of a previous oral
      hygiene instruction was also reported. Seizure and statistical analysis was
      performed using Statistical Package for the Social Sciences (SPSS) 13.0 software.
      Results: The results showed that 94.5 % of the orphans' children have a
      toothbrush and 90.2% among them have toothpaste. 98.2% of residents brushed their
      teeth and 83.3% of those who brushed their teeth do it regularly (daily). 49.4%
      of the orphans' children brushed their teeth vertically while 88.5% of them had
      already oral hygiene instructions. Discussion: Attitudes of resident concerning
      tooth brushing regularity and the used method remains largely insufficient even
      if the orphans were informed of the importance of oral hygiene.

PMID- 30234276
TI  - Roles of cathepsins in pancreatic cancer.
AB  - Pancreatic cancer is an aggressive disease with rapid invasion and metastasis.
      Extracellular matrix degrading enzymes play an important role in cancer cell
      invasion and migration. Cathepsins are a group of proteolytic enzymes, which are
      responsible for the matrix turnover. Among the cathepsins, more number of studies
      have focused upon cysteine cathepsins. The function and activities of these
      enzymes are interwoven and their interplay causes the activation of one another
      by following a proteolytic cascade. This review focuses on differential
      expression of cathepsins in different types of pancreatic cancer and controls,
      importance of cathepsins in various phenomena responsible for tumorigenesis and
      its spread in experimental and human studies. Thus, cathepsins and its expression
      in pancreatic cancer may be used as potential biomarkers and may prove to be
      important therapeutic targets if tested clinically.

PMID- 30234277
TI  - Is laparoscopic cholecystectomy effective in relieving dyspepsia in patients of
      cholelithiasis? A prospective study.
AB  - Background: Laparoscopic cholecystectomy (LC) is routinely done for symptomatic
      gallstone disease; however, its role in relieving dyspeptic symptoms in
      cholelithiasis is controversial. Aim: The study was designed to assess the role
      of laparoscopic cholecystectomy in relieving dyspeptic symptoms in patients
      having cholelithiasis with only dyspeptic symptoms. Methods: Patients with
      cholelithiasis having only dyspeptic symptoms not attributable to other causes
      (like Helicobacter pylori) were subjected to laparoscopic cholecystectomy.
      Dyspepsia scores (Dyspepsia Severity Assessment Score-DSAS and Gastrointestinal
      Quality of Life Index- GIQLI) were measured before and after surgery and analyzed
      using Greenhouse-Geisser, McNemar's and ANOVA tests. Results: 27 patients
      (M:F=1:26, mean age=40.48+/-10.60 years) having dyspepsia with asymptomatic
      gallstones were included in the study. There was significant improvement in DSAS
      (20.11+/-4.36 vs 28.63+/-3.42; p<0.001) and GIQLI(106.11+/-5.77 vs 122.56+/-7.95;
      p<0.001) after 2 months of LC. All symptoms improved individually; relief in
      early satiety and vomiting was the maximum (outcome benefit ratios=0.954, p=0.007
      and 0.937, p=0.005 respectively). Multiple gallstones caused more dyspepsia than
      single (p=0.005). There was no significant difference between H. pylori positive
      and negative groups in terms of improvement of DSAS and GIQLI scores after LC
      (p=0.897 and p=0.375 respectively; however dyspepsia was seen to improve
      significantly within both groups). Conclusion: Dyspepsia may be a symptom of
      gallstone disease, and these patients can benefit from LC especially when early
      satiety and vomiting are the main symptoms. A larger sample size may offer more
      insight.

PMID- 30234278
TI  - Correlation between Serum Hyaluronic Acid with Steatosis, Non alcoholic Steato
      hepatitis and Fibrosis in Patients with Chronic Hepatitis C Virus Infection.
AB  - Background: Hyaluronic acid (HA) is an attractive potential marker for
      noninvasive diagnosis of liver fibrosis instead of liver biopsy for both patients
      and physicians. Aim: To assess the role of HA for diagnosing the progression of
      steatosis to steato-hepatitis (SH) and fibrosis in patients with Chronic
      Hepatitis C virus (HCV) infection. Methods: 90 patients with chronic HCV
      infection, 77 (85.6%) males and 13 (14.4%) females, were included. Blood samples
      were collected for routine laboratory investigations, liver function tests and
      serum HA measurements. A liver biopsy was taken for histopathological
      examination. Results: Steatosis was found in 37 patients (41.1%), fibrosis in 29
      patients (32.2%) and SH in 51 patients (56.7%). The mean serum HA for all
      patients was 86.4+/-48.2 ng/L. HA levels were significantly higher in patients
      with fibrosis (95.6+/-53 vs 54.5+/-3.5) and SH (88.7+/-52 vs 49.9+/-12) than
      those without (P value = 0.001and 0.001 respectively). HA levels were also
      significantly higher in patients with an advanced degree of fibrosis, SH and
      steatosis as compared to those with mild degrees (P value = 0.000, 0.001 and 0.01
      respectively). Positive correlations were found between serum HA and the degree
      of fibrosis, SH and steatosis (P value =0.000 and r = + 0.758, 0.701and 0.727
      respectively). The mean HA cut off value for the diagnosis of fibrosis and SH was
      taken to be 70 and 60 ng/L providing a diagnostic accuracy of 94.1% and 91.6%
      respectively. Conclusion: Serum HA level is a good noninvasive marker for the
      diagnosis of fibrosis and steato-hepatitis in patients with chronic HCV
      infection.

PMID- 30234279
TI  - Elevated levels of serum uric acid and insulin resistance are associated with
      nonalcoholic fatty liver disease among prediabetic subjects.
AB  - Background: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation
      of insulin resistance and serum uric acid (SUA) levels seemed to be elevated
      during this disorder. There is a paucity of data regarding the association of SUA
      with NAFLD in prediabetes. In this context, the present study has been undertaken
      to investigate this association. Methods: In a cross-sectional analytical design,
      a total of 110 prediabetic subjects [M/F; 63/47, age in ranges, 45 (25-68)] were
      recruited in the study and divided into non NAFLD (n = 62) and NAFLD (n = 48)
      group after examined with ultrasonogram. Insulin resistance (HOMA-IR) was
      calculated by homeostasis model assessment. Results: NAFLD subjects had
      significantly higher levels of SUA compared to non NAFLD subjects (6.10 +/- 1.42
      vs. 5.38 +/- 1.14, p = 0.004). They also had significantly higher levels of HOMA
      IR (2.4 +/- 1.09 vs. 1.4 +/- 0.45, p < 0.001). In binary logistic regression
      analysis, HbA1c (OR = 3.505, p = 0.002), SUA (OR = 1.514, p = 0.023) and HOMA-IR
      (OR = 1.478, p = 0.029) were found to be significant determinants of NAFLD after
      adjusting the effects of BMI and triglyceride (TG). In multiple linear regression
      analysis, SUA showed significant positive association with HOMA-IR (beta = 0.355,
      p = 0.027) and TG (beta = 0.325, p = 0.033) after adjusting the effects of BMI
      and HbA1c. Conclusions: Increased levels of serum uric acid are significantly
      associated with NAFLD and this association seemed to be mediated by insulin
      resistance among prediabetic subjects.

PMID- 30234280
TI  - Translation and validation of the Hindi version of chronic liver disease
      questionnaire (CLDQ) for the assessment of health related quality of life in
      patient with chronic liver disease in India.
AB  - Background: Chronic liver disease questionnaire (CLDQ) is an established disease
      specific tool to assess the health related quality of life (HRQOL) in patients
      with CLD irrespective of the etiology and severity. The objective of the study
      was to develop the Hindi language version of CLDQ and to assess the validity of
      the Hindi CLDQ. Methods: CLDQ was adapted into Hindi language by following a
      standard method of forward and back-translation by two bilingual translators,
      revision by expert panel and formulation of a consensual version followed by
      pilot testing and appropriate modifications before final administration. Hindi
      CLDQ along with short form 36 (SF-36) were administered in 494 patients with
      chronic liver disease (CLD) and 103 healthy controls (HC). To assess
      reproducibility, Hindi CLDQ was re-administered in a subsample of 20 patients.
      Internal consistency was assessed by Cronbach's alpha coefficient. Structural
      validity was assessed by exploratory factor analysis and construct validity was
      assessed with help of correlation of SF-36 scores and CLDQ pattern across disease
      severity groups. Results: The Cronbach's alpha coefficient was 0.93 and intra
      class coefficient correlation was 0.88 for the average CLDQ score, suggestive of
      good reliability. An inverse relationship of the average CLDQ score with the
      disease severity (CLDQ score of Child A vs. B vs. C = 5.2+/-1.10 vs. 4.73+/-1.24
      vs. 4.15+/-1.19 respectively; p<0.001) and good correlation with SF-36 scores
      (average CLDQ score with PCS & MCS; r=0.63 & 0.55; p<0.001) was suggestive of
      good validity of Hindi CLDQ. The factor analysis identified 6 domains accounting
      for 62% of variability. The derived cut-off of 6 for the average CLDQ had the AUC
      of 0.826 with a sensitivity of 76.7. Conclusion: Hindi version of CLDQ is found
      to be a reliable and a valid tool comparable to the original English version. The
      HRQOL of patients with CLD is lower than healthy controls and HRQOL decreases
      with increase in disease severity.

PMID- 30234281
TI  - Surgical management and prognosis of perforation secondary to typhoid fever.
AB  - Introduction: Enteric perforation is a serious complication of typhoid fever and
      the condition has a high morbidity and mortality in many developing countries
      including India. No consensus exists concerning the best procedure to be
      performed in these cases. Aim: Aim: The purpose of this study was to analyse our
      clinical experience in surgical management of enteric perforation and to
      determine the prognostic factors associated with morbidity and mortality.
      Methods: It was a prospective study of patients who underwent surgery for typhoid
      intestinal perforation at SMS Medical College and Hospital, Jaipur, India,
      between April 2012 and October 2013. Laparotomy was performed by a midline
      incision. Management of perforation was based on the intraoperative findings and
      the procedure to be performed was decided by the operating surgeon. Results: 88
      patients were studied with a male to female ratio of 6.3:1. The mean age was 36.4
      years. The peak incidence was between 21 to 30 years. All the patients presented
      with abdominal pain and distension. More than 90% patients showed free gas under
      diaphragm. 71% patients had a single perforation and 97% patients had
      perforations confined to ileum. Debridement with double layered closure was
      performed in about 58% patients, ileostomy in 25% and resection anastomosis in
      18% of patients. Overall complication rate was 44.3% with surgical site infection
      being the most common morbidity. The mortality rate was 17.1% which was
      significantly affected by perforation-admission interval of more than 48 hours,
      number of perforations and occurrence of postoperative complications. Conclusion:
      Typhoid fever leading to development of intestinal perforation continues to be a
      significant health problem with a high morbidity and mortality especially in
      rural India. The management of the disease requires an early and appropriate
      surgical intervention.

PMID- 30234282
TI  - Metastatic hepatocellular carcinoma to the scalp: A diagnostic dilemma on
      cytology and solved on immunohistochemistry.

PMID- 30234283
TI  - EUS guided drainage of intrahepatic pancreatic pseudocyst.

PMID- 30234284
TI  - Non-alcoholic steatohepatitis (NASH) in non-obese children.

PMID- 30234286
TI  - Mucin hypersecreting bile duct neoplasm.

PMID- 30234285
TI  - Primary Ewing's sarcoma /primitive neuroectodermal tumor of stomach.

PMID- 30234287
TI  - Polyethyleneimine-Coated Manganese Oxide Nanoparticles for Targeted Tumor PET/MR
      Imaging.
AB  - A Mn3O4 nanoparticle (NP)-based dual-modality probe has been developed for tumor
      positron emission tomography (PET)/magnetic resonance (MR) imaging. The dual
      modality imaging probe was constructed by modifying multifunctional
      polyethyleneimine (PEI)-coated Mn3O4 NPs with folic acid (FA), followed with the
      radiolabeling with 64Cu. The formed imaging probe was utilized for PET/MR imaging
      of human cervical cancer mouse xenografts, which overexpress folate receptor
      (FR). The PEI-coated Mn3O4 NPs were synthesized using a solvothermal approach via
      decomposition of acetylacetone manganese. Multifunctional groups, including
      fluorescein isothiocyanate (FI), PEGylated FA, and NOTA chelator, were then
      sequentially loaded onto the surface of the amine groups of the Mn3O4 NPs. The
      remaining PEI amines were neutralized by the acetylation reaction. The resulting
      NOTA-FA-FI-PEG-PEI-Ac-Mn3O4 NPs were fully characterized and evaluated in vitro
      and successfully radiolabeled with 64Cu for tumor PET/MR imaging in small
      animals. In vivo blocking experiments were performed to determine the FR binding
      specificity of NPs. PET imaging results demonstrated that 64Cu-labeled Mn3O4 NPs
      display good tracer uptake in the FR-expressing HeLa tumors (tumor-to-muscle
      (T/M) ratio: 5.35 +/- 0.31 at 18 h postinjection (pi)) and substantially reduced
      tracer uptake in the FR-blocked HeLa tumors (T/M ratio: 2.78 +/- 0.68 at 18 h
      pi). The ex vivo data, including PET imaging and biodistribution, further
      confirmed the tumor binding specificity of the 64Cu-labeled Mn3O4 NPs. Moreover,
      the FR-targeted Mn3O4 NPs exhibited efficient T1-weighted MR imaging (MRI),
      leading to the precise tumor MRI at 18 h pi. PET/MR imaging with the 64Cu-NOTA-FA
      FI-PEG-PEI-Ac-Mn3O4 NPs may offer a new quantitative approach to precisely
      measure the FR in tumors. The strategy of incorporating PEI nanotechnology into
      the construction of new biomaterials may be applied for the construction of novel
      nanoplatforms for cancer diagnosis and therapy.

PMID- 30234288
TI  - Noncovalent PEG Coating of Nanoparticle Drug Carriers Improves the Local
      Pharmacokinetics of Rectal Anti-HIV Microbicides.
AB  - Antiretroviral drug nanocarriers hold great promise for developing anti-human
      immunodeficiency virus (HIV) rectal microbicides. However, challenges remain,
      namely, concerning which properties are more suited for enhancing colorectal
      distribution and retention of microbicide compounds. In this work, we developed
      and assessed the in vitro and in vivo performance of poly(lactic- co-glycolic
      acid) (PLGA)-based nanoparticles (NPs) as carriers for the model drug efavirenz
      (EFV). We particularly focused on the effect of noncovalent poly(ethylene glycol)
      coating of PLGA NPs (PEG-PLGA NPs) conferring a mucus-diffusive behavior on the
      pharmacokinetics (PK) of EFV following rectal administration to mice. Drug-loaded
      PLGA NPs and PEG-PLGA NPs (200-225 nm) were obtained by nanoprecipitation. Both
      types of systems were able to retain native antiretroviral activity of EFV in
      vitro, while featuring lower cytotoxicity against different epithelial cell lines
      and HIV target cells. Also, PLGA NPs and PEG-PLGA NPs were readily taken up by
      colorectal cell lines and mildly reduced EFV permeation while increasing membrane
      retention in Caco-2 and Caco-2/HT29-MTX cell monolayer models. When administered
      intrarectally to CD-1 mice in phosphate-buffered saline (pH 7.4), EFV-loaded PEG
      PLGA NPs consistently provided higher drug levels in colorectal tissues and
      lavages, as compared to free EFV or drug-loaded PLGA NPs. Mean values for the
      area-under-the-curve between 15 min and 12 h following administration were
      particularly higher for PEG-PLGA NPs in distal and middle colorectal tissues,
      with relative bioavailability values of 3.7 and 29, respectively, as compared to
      free EFV (2.2 and 6.0 over PLGA NPs, respectively). Systemic exposure to EFV was
      reduced for all treatments. NPs were further shown safe after once-daily
      administration for 14 days, as assessed by histological analysis of colorectal
      tissues and chemokine/cytokine assay of rectal lavages. Overall, PEG-PLGA NPs
      demonstrated to be safe carriers for rectal microbicide drug delivery and able to
      provide enhanced local PK that could be valuable in preventing rectal HIV
      transmission.

PMID- 30234289
TI  - Investigating Glyoxylate-Mediated Transamination Using Dipeptide Arrays and
      Proteomic Peptide Mixtures.
AB  - Glyoxylate-mediated transamination (GT) is a classic, potentially general, and N
      terminus-specific protein modification method useful for the preparation of
      bioconjugates. However, there is a lack of information on whether and how readily
      a particular N-terminal amino acid (in the context of a peptide chain) can be
      converted to the 2-oxoacyl moiety under GT conditions. Here, we conducted a
      systematic investigation of GT using membrane-bound dipeptide arrays that include
      all the 400 possible dipeptide combinations of the 20 genetically encoded amino
      acids. This colorimetric method offers a convenient way to assess the GT reaction
      tendency of N-terminal residues by the naked eye. It also provides interesting
      information about the effect of the second residues on GT, which has not been
      reported previously. In addition, we also designed a proteomics approach to study
      GT in solution using tryptic peptide mixtures, which not only confirmed many of
      our findings in peptide array assays but also revealed potential side reaction
      products. Taken together, our studies will make the future use of GT for protein
      modification in a much more predictable way.

PMID- 30234291
TI  - Advanced Smart Nanomaterials with Integrated Logic-Gating and Biocomputing: Dawn
      of Theranostic Nanorobots.
AB  - Accurate and precise drug delivery is the key to successful therapy. Monoclonal
      antibodies, which can transport therapeutic payload to cells expressing specific
      markers, have paved the way for targeted drug delivery and currently show
      tremendous clinical success. However, in those abundant cases, when a disease
      cannot be characterized by a single specific marker, more sophisticated drug
      delivery systems are required. To enhance targeting accuracy, diverse smart
      materials have been proposed that can also react to stimuli like variations of
      pH, temperature, magnetic field, etc. Furthermore, over the past few years a new
      category of smart materials has emerged, which can not only respond to virtually
      any biochemical or physical stimulus but also simultaneously analyze several cues
      and, moreover, can be programmed to use Boolean logic for such analysis. These
      advanced biocomputing agents have the potential to become a basis for future
      nanorobotic devices that could overcome some of the grand challenges of modern
      biomedicine. Here, with a brief introduction to the multidisciplinary field of
      biomolecular computing, we will review the concepts of nanomaterials with built
      in biocomputing capabilities, which can be potentially used for drug delivery and
      other theranostic applications.

PMID- 30234292
TI  - Biphasic-Scanning Ion Conductance Microscopy.
AB  - A concentration gradient driven imaging mechanism is described for scanning ion
      conductance microscopy (SICM). Two different solution phases, one filling a
      double-barrel pipet and one in the bath, are used to afford probe control and
      imaging under nonstandard SICM conditions. Under these conditions, solutions with
      no added electrolyte can be utilized as the bath solution. Further, both positive
      and negative feedback modes are exhibited as the probe approaches the surface. We
      term this method biphasic-SICM (BP-SICM). Technical details of implementing BP
      SICM and operational principles are described herein.

PMID- 30234294
TI  - Plasmonic Interface Modified with Graphene Oxide Sheets Overlayer for Sensitivity
      Enhancement.
AB  - A novel strategy to modify the plasmonic interface by spin-coating an overlayer
      of graphene oxide sheets (GOSs) on top of the surface plasmon resonance (SPR)
      sensor is proposed and demonstrated. Thanks to the excellent electrical
      conductivity, large surface area, and high-refractive index of the GOSs layer,
      the GOSs-modified SPR (GOSs-SPR) sensor achieves an improved sensitivity in the
      detection of bulky refractive index solutions and bovine serum albumin (BSA)
      solutions. The maximum sensitivity of 2715.1 nm/RIU achieved by three spin
      coatings shows an enhancement of 20.2% than the case without the modification of
      the GOSs overlayer. Benefiting from the large surface area and abundant surface
      functional groups, the GOSs-SPR sensor has a greater sensitivity enhancement (up
      to 39.35%) in the detection of the BSA molecules. Most importantly, we have
      firstly experimentally demonstrated that the GOSs overlayer with thickness over
      hundreds nanometers can still lead to a great enhancement of sensitivity of SPR
      sensors. Additionally, the proposed modification method for the plasmonic
      interface is a simple and effective strategy to boost the sensitivity in a
      chemical-free and environment-friendly manner, without additional chemical or
      biological amplification steps. These unique features make the proposed GOSs-SPR
      biosensor a low-cost and biocompatible platform in the fields of biochemical
      sensing, drug screening, and environmental monitoring.

PMID- 30234293
TI  - Halogen Bond Asymmetry in Solution.
AB  - Halogen bonding is the noncovalent interaction of halogen atoms in which they act
      as electron acceptors. Whereas three-center hydrogen bond complexes, [D...H...D]+
      where D is an electron donor, exist in solution as rapidly equilibrating
      asymmetric species, the analogous halogen bonds, [D...X...D]+, have been observed
      so far only to adopt static and symmetric geometries. Herein, we investigate
      whether halogen bond asymmetry, i.e., a [D-X...D]+ bond geometry, in which one of
      the D-X bonds is shorter and stronger, could be induced by modulation of
      electronic or steric factors. We have also attempted to convert a static three
      center halogen bond complex into a mixture of rapidly exchanging asymmetric
      isomers, [D...X-D]+ ? [D-X...D]+, corresponding to the preferred form of the
      analogous hydrogen bonded complexes. Using 15N NMR, IPE NMR, and DFT, we prove
      that a static, asymmetric geometry, [D-X...D]+, is obtained upon desymmetrization
      of the electron density of a complex. We demonstrate computationally that
      conversion into a dynamic mixture of asymmetric geometries, [D...X-D]+ ? [D
      X...D]+, is achievable upon increasing the donor-donor distance. However, due to
      the high energetic gain upon formation of the three-center-four-electron halogen
      bond, the assessed complex strongly prefers to form a dimer with two static and
      symmetric three-center halogen bonds over a dynamic and asymmetric halogen bonded
      form. Our observations indicate a vastly different preference in the secondary
      bonding of H+ and X+. Understanding the consequences of electronic and steric
      influences on the strength and geometry of the three-center halogen bond provides
      useful knowledge on chemical bonding and for the development of improved halonium
      transfer agents.

PMID- 30234295
TI  - Active Natural Product Scaffolds against Trypanosomatid Parasites: A Review.
AB  - Neglected tropical diseases caused by trypanosomatid parasites are a continuing
      and escalating problem, which devastate the less economically developed cultures
      in countries in which they are endemic by impairing both human and animal health.
      Current drugs for these diseases are regarded as out-of-date and expensive, with
      unacceptable side-effects and mounting parasite resistance, meaning there is an
      urgent need for new therapeutics. Natural products have long been a source of
      potent, structurally diverse bioactive molecules. Herein are reviewed natural
      products with reported trypanocidal activity, which have been clustered based on
      core structural similarities, to aid the future discovery of new trypanocidal
      core motifs with potential routes to synthetically accessible natural product
      cores suggested.

PMID- 30234296
TI  - Self-Assembly of Core-Corona beta-Glucan into Stiff and Metalizable
      Nanostructures from 1D to 3D.
AB  - The development of self-assembly strategies for well-studied biopolymers is an
      important route to complex and functional nanostructures. Here, we report the
      self-assembly of a stiff polysaccharide, formylated yeast beta-glucan, into
      multiple highly ordered nanostructures from 1D to 3D. This polysaccharide could
      fold into a two-component helix that consisted of a rod-like helical core and
      flexible coronas. Annealing in formic acid can trigger the cross-linking of the
      coronas, resulting in the packing of helices into rod-like, sheet-like, or tube
      like supramolecular nanostructures. The specific morphology of the resultant
      assemblies can be controlled by different annealing conditions such as annealing
      speed or polymer concentrations. Owing to the presence of reductant formyl
      groups, these beta-glucan nanostructures can reduce silver ions in situ, leading
      to the guided assembly of ultrathin silver nanowires, silver-polymer nanorods,
      and silver-polymer necklaces.

PMID- 30234297
TI  - Surfaces/Interfaces Modification for Vacancies Enhancing Lithium Storage
      Capability of Cu2O Ultrasmall Nanocrystals.
AB  - Theoretically, Cu2O delivers a poor Li storage capacity ~373.9 mA h g-1 based on
      a so-called conversion reaction (Cu2O + 2Li -> 2Cu + Li2O). Herein, we broke
      through the bottleneck and acquired an impressive lithium storage capability
      (1122 mA h g-1) tripled more than the theoretical one by an in situ
      surface/interface engineering process for the first time. The surface/interface
      modification enabled us to fabricate ultrasmall nanocrystals of Cu2O with Cu
      vacancies (VCu) of high concentration, somewhat like monovalent anion doping.
      Except for the conversion reaction-type capacity, VCu enhancing intercalation
      pesudocapacitance in Cu2O and its reduction product-Cu also contributed a lot to
      the Li-storage capability. First-principles calculation substantiated that
      intercalation energy of Li was severely lowered for both Cu vacancy-rich Cu2O and
      Cu comparing with their stoichiometric counterparts. Another important factor for
      the enhancement was the surface/interface organic species themselves which could
      reversibly store Li by redox reactions. The surface/interface modification for
      vacancies, vacancy inheritance from metal oxide to single metal, and vacancy
      enhancing Li-storage capability in metal oxide and single metal all will inspire
      us a lot in fabricating new-generation advanced electrodes for rechargeable
      batteries.

PMID- 30234298
TI  - Nitric Oxide-Releasing Cyclodextrins.
AB  - A series of secondary amine-modified cyclodextrin (CD) derivatives was
      synthesized with diverse exterior terminal groups (i.e., hydroxyl, methyl,
      methoxyl, and primary amine). Subsequent reaction with nitric oxide (NO) gas
      under alkaline conditions yielded N-diazeniumdiolate-modified CD derivatives.
      Adjustable NO payloads (0.6-2.4 MUmol/mg) and release half-lives (0.7-4.2 h) were
      achieved by regulating both the amount of secondary amine precursors and the
      functional groups around the NO donors. The bactericidal action of these NO
      releasing cyclodextrin derivatives was evaluated against Pseudomonas aeruginosa,
      a Gram-negative pathogen, with antibacterial activity proving dependent on both
      the NO payload and exterior modification. Materials containing a high density of
      NO donors or primary amines exhibited the greatest ability to eradicate P.
      aeruginosa. Of the materials prepared, only the primary amine-terminated
      heptasubstituted CD derivatives exhibited toxicity against mammalian L929 mouse
      fibroblast cells. The NO donor-modified CD was also capable of delivering
      promethazine, a hydrophobic drug, thus demonstrating potential as a dual-drug
      releasing therapeutic.

PMID- 30234299
TI  - Nematicidal Cyclic Lipodepsipeptides and a Xanthocillin Derivative from a
      Phaeosphariaceous Fungus Parasitizing Eggs of the Plant Parasitic Nematode
      Heterodera filipjevi.
AB  - The new cyclic lipodepsipeptide ophiotine (1), two new arthrichitin derivatives
      named arthrichitins B (4) and C (5), a new xanthocillin-like alkaloid, xanthomide
      Z (2), and the previously described arthrichitin (3) were isolated from the
      liquid culture broth of a nematode-associated fungus with affinities to the genus
      Ophiosphaerella. The structural elucidation and determination of the absolute
      configuration of the new molecules were accomplished using a combination of
      spectroscopic and chemical techniques, including 1D and 2D NMR, HRMS, and
      Marfey's analysis. Opiotine (1) displayed moderate nematicidal activity against
      the host nematode ( Heterodera filipjevi), while xanthomide Z (2) exhibited very
      weak activity. Arthrichitin C (5) showed very weak cytotoxic effects on several
      cancer cell lines, with IC50 values in the range of 24-33 MUM. Xanthomide Z is
      among few xanthocillin derivatives that comprise formamide functions instead of
      the cyano functions that are usually observed in this class of fungal alkaloids.

PMID- 30234300
TI  - Structure-Based Design of 1-Heteroaryl-1,3-propanediamine Derivatives as a Novel
      Series of CC-Chemokine Receptor 5 Antagonists.
AB  - CC-chemokine receptor 5 (CCR5) is an attractive target for preventing the entry
      of human immunodeficiency virus 1 (HIV-1) into human host cells. Maraviroc is the
      only CCR5 antagonist, and it was marketed in 2007. To overcome the shortcomings
      of maraviroc, structure-based drug design was performed to minimize CYP450
      inhibition and to enhance anti-HIV potency and bioavailability. Thirty-four novel
      1-heteroaryl-1,3-propanediamine derivatives (1-34) were synthesized, displaying
      CCR5-antagonist activities in the 2.3-296.4 nM range. Among these, compounds 21
      and 34 were the most potent CCR5 antagonists, with excellent in vitro anti-HIV-1
      activity, low cytotoxicity, and an acceptable pharmacokinetic profile.
      Furthermore, the X-ray crystal structures of compounds 21 and 34 bound to CCR5
      were determined at 2.8 A resolution. Compound 34 exhibited no CYP450-inhibition
      activity at 25 MUM, which overcomes the potential drug-drug interaction of
      maraviroc. Compound 34 represents a promising drug candidate for HIV-infection
      treatment.

PMID- 30234301
TI  - Alkylation of the K-Region in a Sterically Hindered Pyrene Carboxamide via
      Directed Reaction with Alkyllithiums under Air.
AB  - Sterically hindered N,2,7-tri- tert-butylpyrene-1-carboxamide treated with n
      BuLi, i-BuLi, s-BuLi, and n-HexLi in THF in the presence of TMEDA and air
      afforded trans- N,2,7-tri- tert-butylpyrene-10-alkyl-9-hydroxy-9,10-dihydropyrene
      1-carboxamides in 63-74% yield. Trifluoroacetic acid promoted dehydration of
      these compounds gave 10-alkyl derivatives of the starting amide in 79-89% yield.
      The minor products of this reaction were deamidated compounds, 4-alkyl-2,7-di-
      tert-butylpyrenes.

PMID- 30234302
TI  - Precursor Control over the Self-Assembly of Organic Cages via Imine Condensation.
AB  - A series of tetrahedral cages and triangular prisms have been self-assembled by
      condensing ostensibly analogous trisformyl precursors with tris or bisamino
      linkers under the nominally reversible reaction conditions in the manner of
      either [4 + 4] or [2 + 3], respectively. We observed that the conformations of
      the trisformyl precursors have great impact on the self-assembly pathway and
      product yields. More specifically, a rigid and planar precursor favors the
      formation of prisms while a more twisted one favors tetrahedron. As a comparison,
      a more flexible precursor, which is able to adopt both relatively planar and
      twisted conformations, is capable of producing both prisms and tetrahedrons in
      relatively high yields. Both experimental and theoretical results indicate that
      the self-assembly preference is ascribed to subtle variations in the level of pi
      pi and CH-pi interactions that act as the driving forces for the formation of
      prisms and tetrahedrons, respectively.

PMID- 30234303
TI  - The Sensitivity of Computational Protein Folding to Contact Map Perturbations:
      The Case of Ubiquitin Folding and Function.
AB  - Ubiquitin is a small model protein, commonly used in protein folding experiments
      and simulations. We simulated ubiquitin using a well-tested structure-based model
      coarse-grained to a Calpha level (Calpha-SBM) and found that the simulated
      folding route did not agree with the experimentally observed one. Simulating the
      Calpha-SBM with a cutoff contact map, instead of a screened contact map, switched
      the folding route with the new route matching the experimental route. Thus, the
      simulated folding of ubiquitin is sensitive to contact map definition. The
      screened contact map, which is used in folding simulations because it captures
      protein folding cooperativity, removes contacts in which the atoms in contact are
      occluded by a third atom and is less sensitive to the value of the cutoff
      distance in well-packed regions of the protein. In sparsely packed regions, the
      larger cutoff distance creates bridging contacts between atoms which are
      separated by voids. Such contacts do not seem to affect the folding of most
      proteins, including those of the ubiquitin fold. However, the surface of
      ubiquitin has several protruding functional side chains which naturally create
      bridging contacts. Together, our results show that subtle structural features of
      a protein that may not be apparent by mere observation can be identified by
      comparing folding simulations of SBMs in which these features are differently
      encoded. When such structural features are preserved for functional reasons,
      differences in computational folding can be leveraged to identify functional
      features. Notably, such features are accessible to a gradation of SBMs even in
      commonly studied proteins such as ubiquitin.

PMID- 30234304
TI  - Iridium-Catalyzed Highly Regioselective and Diastereoselective Allylic
      Etherification To Access cis-2,6-Disubstituted Dihydropyridinones.
AB  - A highly regio- and diastereoselective method to access cis-2,6-disubstituted
      dihydropyridinones under mild conditions by an iridium-catalyzed allylic
      etherification is reported. cis-2,6-Disubstituted dihydropyridinones are
      important precursors for the de novo synthesis of the corresponding piperidine
      alkaloids and iminosugars. This strategy features a broad substrate scope, high
      yields, and excellent regio- and diastereoselectivities. A pi-allyl-Ir
      intermediate is involved in the mechanism. The strong A1,3-strain from the tosyl
      group may also favor the formation of cis-products in this transformation.

PMID- 30234305
TI  - Structural Analyses of Alanine Trimer and Tetramer Crystals with Antiparallel and
      Parallel beta-Sheet Structures Using Solid-State 1H Spin-Diffusion 2D Correlation
      NMR Spectroscopy.
AB  - Poly-l-alanine (PLA) sequences are key elements of the crystalline domains of
      spider dragline and wild silkworm silks. In the present work, 1H spin-diffusion
      two-dimensional (2D) correlation NMR spectra were observed for selectively
      deuterated (Ala)3 and (Ala)4 crystals to develop the analytical method for the
      structure of PLA sequences. The build-up curves of the cross peaks for three
      kinds of 1H pairs in selectively deuterated (Ala)3 and (Ala)4 crystals were
      observed to obtain spin-diffusion rate constant k j, k from relaxation master
      equations P i, j(taum). The k j, k values subsequently lead to effective
      interproton distance r j, keff (obs) values for individual proton-proton pairs,
      which include intra- and intermolecular contributions. The r j, keff (obs) values
      were compared to r j, keff (calc) values obtained from the experimentally
      determined atomic coordinates of antiparallel (AP) beta-sheet (Ala)3 and (Ala)4
      and parallel (P) beta-sheet of (Ala)3 and (Ala)4 crystals. The agreement between
      the r j, keff (obs) and r j, keff (calc) values was good for AP beta-sheet (Ala)3
      and (Ala)4 crystals but poor for P beta-sheet (Ala)3 and (Ala)4 crystals. These
      deviations were obtained from the interproton distances of the interchain
      contributions due to different packing arrangements. The packing arrangements of
      the PLA region are important when considering the relevant structure and the
      mechanical properties of silks.

PMID- 30234306
TI  - Palladium(0)-Catalyzed Intermolecular Cascade Dearomatization Reaction of beta
      Naphthol Derivatives with Propargyl Carbonates.
AB  - A Pd(0)-catalyzed intermolecular cascade dearomatization reaction of beta
      naphthol derivatives with propargyl carbonates was described. In the presence of
      a Pd complex derived from Pd2dba3 and rac-BINAP, various spironaphthalenones were
      obtained in excellent yields (up to 95%) and with high chemoselectivity (C/O >
      20:1) in most cases.

PMID- 30234307
TI  - In Situ TEM Observation of Crystal Structure Transformation in InAs Nanowires on
      Atomic Scale.
AB  - In situ transmission electron microscopy investigation of structural
      transformation in III-V nanowires is essential for providing direct insight into
      the structural stability of III-V nanowires under elevated temperature. In this
      study, through in situ heating investigation in a transmission electron
      microscope, the detailed structural transformation of InAs nanowires from
      wurtzite structure to zinc-blende structure at the catalyst/nanowire interface is
      witnessed on the atomic level. Through detailed structural and dynamic analysis,
      it was found that the nucleation site of each new layer of InAs and catalyst
      surface energy play a decisive role in the growth of the zinc-blende structure.
      This study provides new insights into the growth mechanism of zinc-blende
      structured III-V nanowires.

PMID- 30234308
TI  - Light-Induced Conformational Change of Uracil-Anchored Polythiophene-Regulating
      Thermo-Responsiveness.
AB  - Tuning the electronic structure of a pi-conjugated polymer from the responsive
      side chains is generally done to get desired optoelectronic properties, and it
      would be very fruitful when light is used as an exciting tool that can also
      affect the backbone chain conformation. For this purpose, polythiophene- g-poly-[
      N-(6-methyluracilyl)- N, N-dimethylamino chloride]ethyl methacrylate (PTDU) is
      synthesized. On exposure to diffuse sunlight, the uracil moieties of the grafted
      chains cause the absorption maximum of PTDU solution to show gradual blue shift
      of 87 nm and a gradual blue shift of 46 nm in the emission maximum, quenching its
      fluorescence with time. These effects occur specifically at the absorption range
      of polythiophene (PT) chromophore on direct exposure of light of different
      wavelengths, and the optimum wavelength is found to be 420 nm. Impedance study
      suggests a decrease in charge transfer resistance upon exposure because of
      conformational change of PTDU. Theoretical study indicates that on exposure to
      visible light, uracil moieties move toward the backbone to facilitate
      photoinduced electron transfer between the PT and the uracil, attributing to the
      variation in optoelectronic properties. Morphological and light-scattering
      studies exhibit a decrease in particle size because of coiling of the PT backbone
      and squeezing of the grafted chain on light exposure. The transparent orange
      colored PTDU solution becomes hazy with a hike in emission intensity on addition
      of sodium halides and becomes reversibly transparent or hazy on heating or
      cooling. The screening of cationic centers of PTDU by varying halide anion
      concentration tunes the phase transition temperature. Thus, the light-induced
      variation in the backbone conformation is responsible for tuning the
      optoelectronic properties and regulates the thermos-responsiveness of the PTDU
      solution in the presence of halide ions.

PMID- 30234310
TI  - Metal-Free Formal Inverse-Electron-Demand Diels-Alder Reaction of 1,2-Diazines
      with Ynamides.
AB  - A highly effective metal-free formal inverse-electron-demand Diels-Alder reaction
      of 1,2-diazines with ynamides has been developed. This catalytic protocol is more
      environmentally friendly and allows for the construction of 2-aminonaphthalenes
      and 2-aminoanthracenes from 1,2-diazines and ynamides in good to high yields with
      wide diversity and functional group tolerance.

PMID- 30234309
TI  - Glucosyltransferase Capable of Catalyzing the Last Step in Neoandrographolide
      Biosynthesis.
AB  - ApUGT, a diterpene glycosyltransferase from Andrographis paniculata, could
      transfer a glucose to the C-19 hydroxyl moiety of andrograpanin to form
      neoandrographolide. This glycosyltransferase has a broad substrate scope, and it
      can glycosylate 26 natural and unnatural compounds of different structural types.
      This study provides a basis for exploring the glycosylation mechanism of ent
      labdane-type diterpenes and plays an important role in diversifying the
      structures used in drug discovery.

PMID- 30234312
TI  - Asymmetric Calpha-Alkylation of Proline via Chirality Transfers of
      Conformationally Restricted Proline Derivative: Application to the Total
      Synthesis of (-)-Amathaspiramide F.
AB  - An efficient strategy for the asymmetric synthesis of Calpha-tetrasubstituted
      proline derivatives from proline has been established. A nitrogen-fused bicyclic
      system was devised to control the stereodynamics of proline. Through N
      quaternizations with allylic electrophiles followed by [2,3]-rearrangements, the
      bicyclic proline system delivered enantioenriched Calpha-tetrasubstituted
      prolines. This strategy was applied to the concise total synthesis of (-)
      amathaspiramide F.

PMID- 30234311
TI  - High-Precision Single-Molecule Characterization of the Folding of an HIV RNA
      Hairpin by Atomic Force Microscopy.
AB  - The folding of RNA into a wide range of structures is essential for its diverse
      biological functions from enzymatic catalysis to ligand binding and gene
      regulation. The unfolding and refolding of individual RNA molecules can be probed
      by single-molecule force spectroscopy (SMFS), enabling detailed characterization
      of the conformational dynamics of the molecule as well as the free-energy
      landscape underlying folding. Historically, high-precision SMFS studies of RNA
      have been limited to custom-built optical traps. Although commercial atomic force
      microscopes (AFMs) are widely deployed and offer significant advantages in ease
      of-use over custom-built optical traps, traditional AFM-based SMFS lacks the
      sensitivity and stability to characterize individual RNA molecules precisely.
      Here, we developed a high-precision SMFS assay to study RNA folding using a
      commercial AFM and applied it to characterize a small RNA hairpin from HIV that
      plays a key role in stimulating programmed ribosomal frameshifting. We achieved
      rapid data acquisition in a dynamic assay, unfolding and then refolding the same
      individual hairpin more than 1,100 times in 15 min. In comparison to measurements
      using optical traps, our AFM-based assay featured a stiffer force probe and a
      less compliant construct, providing a complementary measurement regime that
      dramatically accelerated equilibrium folding dynamics. Not only did kinetic
      analysis of equilibrium trajectories of the HIV RNA hairpin yield the traditional
      parameters used to characterize folding by SMFS (zero-force rate constants and
      distances to the transition state), but we also reconstructed the full 1D
      projection of the folding free-energy landscape comparable to state-of-the-art
      studies using dual-beam optical traps, a first for this RNA hairpin and AFM
      studies of nucleic acids in general. Looking forward, we anticipate that the ease
      of-use of our high-precision assay implemented on a commercial AFM will
      accelerate studying folding of diverse nucleic acid structures.

PMID- 30234313
TI  - Structures and Synthesis of Hitoyopodins: Bioactive Aromatic Sesquiterpenoids
      Produced by the Mushroom Coprinopsis cinerea.
AB  - The structures of sesquiterpenoids hitoyopodin A (1) and its hydroxy derivatives
      2 and 3 from the mushroom Coprinopsis cinerea are reported. Their absolute
      structures (1-3) with a benzoxabicyclo[3.2.1]octane core were determined by
      spectroscopy, X-ray crystallography, and total synthesis of 1. Compound 1
      displays antiproliferative activity against HL-60 cancer cells and the malarial
      parasite Plasmodium falciparum. It is proposed that 1 acts as a crucial precursor
      in the biosynthesis of 2, 3, and lagopodins.

PMID- 30234314
TI  - Gender differences in reading and writing achievement: Evidence from the National
      Assessment of Educational Progress (NAEP).
AB  - A frequently observed research finding is that females outperform males on tasks
      of verbal and language abilities, but there is considerable variability in effect
      sizes from sample to sample. The gold standard for evaluating gender differences
      in cognitive ability is to recruit a large, demographically representative
      sample. We examined 3 decades of U.S. student achievement in reading and writing
      from the National Assessment of Educational Progress to determine the magnitude
      of gender differences (N = 3.9 million), and whether these were declining over
      time as claimed by Feingold (1988). Examination of effect sizes found a
      developmental progression from initially small gender differences in Grade 4
      toward larger effects as students progress through schooling. Differences for
      reading were small-to-medium (d = -.32 by Grade 12), and medium-sized for writing
      (d = -.55 by Grade 12) and were stable over the historical time. Additionally,
      there were pronounced imbalances in gender ratios at the lower left and upper
      right tails of the ability spectrum. These results are interpreted in the context
      of Hyde's (2005) gender similarities hypothesis, which holds that most
      psychological gender differences are only small or trivial in size. Language and
      verbal abilities represent one exception to the general rule of gender
      similarities, and we discuss the educational implications of these findings.
      (PsycINFO Database Record

PMID- 30234315
TI  - Can you get the magic back? The moderating effect of passion decay beliefs on
      relationship commitment.
AB  - The present research introduces the construct of a decay theory of passion-a lay
      belief that romantic passion decline is irreversible-and investigates how this
      construct interacts with existing levels of passion for one's romantic partner to
      predict lower relationship commitment and greater pursuit of romantic
      alternatives. Across three studies employing experimental and nonexperimental
      procedures-and a set of meta-analytic syntheses including additional studies
      results generally supported the hypotheses that, although low passion is linked
      to lower commitment and greater pursuit of romantic alternatives, such effects
      are stronger when adherence to decay beliefs is high rather than low. These
      effects tended to be independent of effects of destiny and growth theories (Knee,
      1998), a related set of lay theories in the domain of relationships. Mediated
      moderation analyses revealed that the moderating effect of decay theories on
      relationship commitment mediates the moderating effect of decay theories on the
      link between low passion and the pursuit of romantic alternatives. Discussion
      addresses the possibility that changing one's beliefs surrounding the nature of
      romantic passion may be an important, but previously overlooked, means for
      preventing one from prematurely abandoning an otherwise satisfying relationship.
      (PsycINFO Database Record

PMID- 30234316
TI  - Implicit self-criminal cognition and its relation to criminal behavior.
AB  - Three studies adopted implicit social cognition theory and methodology to
      understand criminal cognition outside of conscious awareness or control,
      specifically by testing whether individual differences in implicit associations
      between the self and the group criminals are related to criminal behavior. A
      Single Category Implicit Association Test measured self-criminal associations
      across 3 adult samples-2 from Newark, New Jersey, a high-crime United States
      city, and an adult national sample from the United States. Then, all participants
      reported their criminal behavior in 2 cross-sectional design studies and 1
      longitudinal design study. Consistent with an additive model of implicit and
      explicit cognition, studies generally demonstrated that strong implicit self
      criminal associations increased the odds of committing a criminal act, even after
      accounting for explicit self-criminal cognition, past criminal behavior, and/or
      criminal-related demographics. This research suggests that implicit self-criminal
      associations serve as a cognitive marker for criminal behavior. Furthermore, the
      present research calls into question criminal justice policies and practices that
      assume that criminal behavior is exclusively driven by criminal intent. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30234317
TI  - Is interviewer support associated with the reduced reluctance and enhanced
      informativeness of alleged child abuse victims?
AB  - Child maltreatment victims are often reluctant to report abuse when formally
      interviewed. Evidence-based guidelines like the National Institute of Child
      Health and Human Development Standard Investigative Interview Protocol do not
      adequately address such reluctance because they are focused on cognitive rather
      than socioemotional strategies. The present study was designed to determine
      whether the Revised National Institute of Child Health and Human Development
      Protocol, which emphasizes supportive interviewing more than the standard
      protocol does, might predict increases in the overall informativeness and
      reductions in the reluctance of alleged victims. A total of 254 interviews, 166
      using the revised protocol and 88 using the standard protocol, were conducted
      with 4.06- to 13.98-year-old children (M = 9.20, SD = 2.49) who disclosed
      multiple incidents of physical abuse by their parents and were thus expected to
      be more reluctant than victims of extrafamilial abuse. We coded indices of
      interviewer support and question types, children's reluctance, and
      informativeness in each utterance during the substantive phases of the
      interviews. The Revised Protocol was associated with better interviewer support
      and questioning as well as reduced reluctance and increased informativeness on
      the part of the children. These findings document the value of training
      interviewers to attend to the socioemotional needs of suspected abuse victims
      during investigative interviews. (PsycINFO Database Record

PMID- 30234318
TI  - Marital satisfaction and mortality in the United States adult population.
AB  - OBJECTIVE: The present study examined the association between marital
      satisfaction and all-cause mortality in a large, representative sample of
      American adults. Gender was evaluated as a potential moderator of this
      association. METHOD: Ratings of marital satisfaction from married adults <90
      years of age (N = 19,246) were extracted from the 1978 - 2010 waves of the
      General Social Survey and linked to mortality data from the National Death Index.
      Discrete-time survival analysis was used to evaluate the association between
      marital satisfaction and mortality. RESULTS: After statistically adjusting for
      demographic variables, the odds of dying for married individuals who described
      their marriage as very happy or pretty happy were significantly lower than the
      odds of dying for married individuals who described their marriage as not too
      happy. The association between marital satisfaction and mortality was not
      moderated by gender. CONCLUSIONS: The significant prospective association between
      marital satisfaction and mortality suggests that reducing marital dissatisfaction
      may increase longevity. Further longitudinal research is warranted to (a)
      replicate the current findings, and (b) evaluate whether increasing marital
      satisfaction through clinical intervention increases longevity. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30234319
TI  - A systematic review of self-report measures of paranoia.
AB  - Paranoia can be conceptualized as consisting of a hierarchy of cognitions,
      ranging from commonly experienced thoughts about less severe perceived threats,
      up to less common, persecutory thoughts about extreme threats, which are
      associated with distressing psychosis. This review systematically appraises self
      report paranoia questionnaires validated for use among the general population;
      the type of paranoia assessed, measurement or psychometric properties, and
      subsequent validation with clinical samples are all considered. A systematic
      literature search was performed using PubMed, Web of Science, and PsycINFO
      databases. Study methodologies and measurement properties were evaluated
      according to COnsenus-based Standards for the selection of health-based
      Measurement Instruments (Mokkink et al., 2012). Twenty-six studies, describing
      the validation of nine paranoia-related questionnaires, were identified.
      Questionnaires were reviewed in relation to the hierarchy of paranoia; with 2
      questionnaires assessing "low-level" paranoia, 4 assessing persecutory thoughts,
      and the remainder assessing paranoia across this continua. Questionnaires
      assessing the full hierarchy of paranoid thoughts, alongside associated
      dimensions such as preoccupation, conviction, and distress, offer the most
      comprehensive assessment of paranoia in both nonclinical and clinical
      populations. Of the measures which do this, the Green et al. (2008) Paranoid
      Thoughts Scale had the strongest evidence for its measurement properties and is,
      therefore, recommended as the most reliable and valid self-report assessment of
      paranoia currently available. However, this review illustrated that generally
      paranoia questionnaires lack high quality evidence for their measurement
      properties. Implications of these findings for clinical practice and research are
      discussed. (PsycINFO Database Record

PMID- 30234320
TI  - Rasch analysis of the Brief Symptom Inventory-18 with African American and White
      students.
AB  - Although the United States offers some of the most advanced psychological
      services in the world, not everyone in the country shares these services equally,
      resulting in health disparities. Health disparities persist when assessments do
      not appropriately measure different populations' mental health problems. To
      address this assessment issue, we conducted principal axis factoring,
      confirmatory factor analysis, and Rasch analyses to assess the psychometric
      characteristics of the Brief Symptom Inventory-18 (BSI-18) to evaluate whether
      the BSI is culturally appropriate for assessing African American students'
      psychological distress. The dimensional structure of the BSI was first identified
      and held up under cross-validation with a second sample and a white sample. The
      measure was unidimensional among African American and white students. Our results
      suggested BSI in our samples presented characteristics such as low person
      separation, stability across samples, and little differential item functioning.
      Most African American and white students identified themselves on the low end of
      the categories in a 0-4 rating scale, indicating their low endorsement of the
      items on the BSI. Rasch analyses were completed with the original scale but also
      collapsing the scale to three points, with some increase in separation and
      reliability for the collapsed scale. As anticipated, differences in mean BSI
      scores were found for mental health-related variables. Implications for theory
      and research on multicultural health scales are discussed as are effects of item
      skewness on analyses. (PsycINFO Database Record

PMID- 30234321
TI  - Complementary surrounds explain diverse contextual phenomena across visual
      modalities.
AB  - Context is known to affect how a stimulus is perceived. A variety of illusions
      have been attributed to contextual processing-from orientation tilt effects to
      chromatic induction phenomena, but their neural underpinnings remain poorly
      understood. Here, we present a recurrent network model of classical and
      extraclassical receptive fields that is constrained by the anatomy and physiology
      of the visual cortex. A key feature of the model is the postulated existence of
      near- versus far- extraclassical regions with complementary facilitatory and
      suppressive contributions to the classical receptive field. The model accounts
      for a variety of contextual illusions, reveals commonalities between seemingly
      disparate phenomena, and helps organize them into a novel taxonomy. It explains
      how center-surround interactions may shift from attraction to repulsion in tilt
      effects, and from contrast to assimilation in induction phenomena. The model
      further explains enhanced perceptual shifts generated by a class of patterned
      background stimuli that activate the two opponent extraclassical regions
      cooperatively. Overall, the ability of the model to account for the variety and
      complexity of contextual illusions provides computational evidence for a novel
      canonical circuit that is shared across visual modalities. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30234322
TI  - Sex differences in mental health symptoms and substance use and their association
      with moral injury in veterans.
AB  - OBJECTIVE: This study examines potential sex differences in 3 types of
      experiences (i.e., atrocities of war, cognitive and emotional changes from
      combat, and leadership failure or betrayal) that may result in moral injury
      (i.e., guilt, shame, inability to forgive one's self, inability to forgive
      others, and withdrawn behavior associated with these three types of experiences).
      In addition, we examine whether moral injury results in different associations
      with mental health and substance use outcomes for female versus male veterans. We
      expected more symptoms of depression and anxiety for women and more symptoms of
      hazardous alcohol use and drug abuse for men. Also, we examined sex as a
      moderator between moral injury and outcomes, expecting stronger relationships
      between moral injury and symptoms of depression and anxiety among women and
      stronger associations between moral injury and alcohol use and drug abuse
      symptoms for men. METHOD: Participants (n = 256; 60.9% [n = 156] males) were a
      community sample of recent-era military personnel who completed a measure of
      morally injurious experiences (MIEs) and associated moral injury. RESULTS: After
      correcting for Type I error rate, sex was not associated with mental health or
      substance use. Further, no Sex * Moral Injury interactions were present; however,
      moral injury significantly positively predicted all negative mental health
      symptoms (depression, anxiety, suicidality, and posttraumatic stress disorder
      [PTSD]) and hazardous alcohol use, but not drug abuse symptoms. CONCLUSIONS:
      Results reveal the need for improved screening and treatment of moral injury and
      integrated treatments that may assess moral injury and associated disorders.
      (PsycINFO Database Record

PMID- 30234323
TI  - Naive 3-day-old domestic chicks (Gallus gallus) are attracted to discrete
      acoustic patterns characterizing natural vocalizations.
AB  - Nonsongbirds can produce rhythmical sounds that, at times, have been shown to be
      meaningful in their communication. This raises the possibility that rhythm is a
      separate ability that might have evolved earlier than song. We asked whether
      nearly completely naive domestic chicks perceive rhythm and respond in specific
      ways to different rhythmic patterns. To do so, specific constituent parameters of
      rhythmicity were used based on the sound of a natural mother hen's cluck. The
      sound samples created ranged from a continuous sound to articulated rhythmic
      patterns of alternating strong and weak events. Chicks' reactivity to the
      patterns was tested over a series of sound exposure experiments by their
      propensity to operate a running wheel toward the acoustic source, a paradigm
      simulating chicks' natural affiliative response to the hen's call. Results showed
      that motor activity increased markedly when acoustic events were discrete
      (compared with continuous), and significantly when accent structure was faster
      (compared with slower rates). Similar to human infants, chicks showed a
      significant preference for pulsed over continuous patterns. Chicks also ran
      harder toward calls with fast strong pulsating events, suggesting that different
      arrangements of events in time can be differently arousing, but independently of
      whether the events were presented in a regular or nonregular fashion. (PsycINFO
      Database Record

PMID- 30234324
TI  - The structure of ape (hominoidea) intelligence.
AB  - We used contemporary psychometric theory of intelligence and confirmatory factor
      analysis to reanalyze data obtained on samples of nonhuman primates administered
      the Primate Cognition Test Battery. Our main goals were to interpret stability of
      the Primate Cognition Test Battery tasks and factors over time and to determine
      whether the cognitive factors that emerge from confirmatory factor analysis for
      apes can be interpreted from the perspective of a major theory of human
      intelligence, namely, the Cattell-Horn-Carroll model. We also analyzed data for
      21/2-year-old children on Wechsler's preschool test to afford a comparison
      between ape and child cognitive factors. Results indicated that multiple
      cognitive abilities provide the best factor solutions for both apes and children,
      and that the ape factors can be meaningfully interpreted from Cattell-Horn
      Carroll theory. (PsycINFO Database Record

PMID- 30234325
TI  - Zebra finches (Taeniopygia guttata) can categorize vowel-like sounds on both the
      fundamental frequency ("pitch") and spectral envelope.
AB  - Humans can categorize vowels based on spectral quality (vowel identity) or pitch
      (speaker sex). Songbirds show similarities to humans with respect to speech sound
      discrimination and categorization, but it is unclear whether they can categorize
      harmonically structured vowel-like sounds on either spectrum or pitch, while
      ignoring the other parameter. We trained zebra finches in two experimental
      conditions to discriminate two sets of harmonic vowel-like sounds that could be
      distinguished either by spectrum or fundamental frequency (pitch). After the
      birds reached learning criterion, they were tested on new sounds that were either
      noise-vocoded versions of the trained sounds (sharing the spectral envelope with
      the trained sounds but lacking fine spectral detail from which pitch could be
      extracted) or sounds lacking the amplified harmonics (sharing only pitch with the
      trained sounds). Zebra finches showed no difference in the number of trials
      needed to learn each stimulus-response mapping. Birds trained on harmonic
      spectrum generalized their discrimination to vocoded sounds, and birds trained on
      pitch generalized their discrimination to harmonic sounds with a flat spectrum.
      These results demonstrate that, depending on the training requirements, birds can
      extract either fundamental frequency or spectral envelope of vowel-like sounds
      and use these parameters to categorize new sounds. (PsycINFO Database Record

PMID- 30234326
TI  - Capuchin monkeys (Cebus [sapajus] apella) show planning in a manual maze task.
AB  - The capacity for planning in nonhuman species has long been an interest of many
      comparative and cognitive psychologists. There is now considerable evidence that
      at least great apes show both motor planning and planning for future needs in
      various contexts and modalities. Few studies, however, have investigated planning
      ability in a monkey species, and most of these exceptions have used computerized
      procedures. To gain a broader view, in the current study, we tested capuchin
      monkeys' capacity for motor planning using the "paddle-box" apparatus, a manual
      maze task originally designed for testing planning skills in apes (Tecwyn,
      Thorpe, & Chappell, 2013). This consisted of a box containing different levels of
      paddles that subjects rotated to drop food into a tube that delivered it to the
      subject. To evaluate subjects' degree of skill in the task, the initial locations
      of the food and the final goal (i.e., the "paths" the food could take) were
      chosen according to the probability of retrieving the reward, starting with those
      that gave the highest probability of success and moving sequentially to those
      with the lowest probability. Most subjects solved all levels of difficulty in the
      task, and capuchin monkeys succeeded as a group in a generalization test with
      novel paths. These findings demonstrate that some monkeys, like apes, show
      planning in different contexts and modalities. (PsycINFO Database Record

PMID- 30234327
TI  - Attentional scope, rumination, and processing of emotional information: An eye
      tracking study.
AB  - Rumination is considered as a relatively maladaptive form of repetitive thinking
      that has a marked impact on mood. Individual differences in attentional scope
      have been proposed as an important mechanism rendering some individuals more
      prone to ruminate than others. The attentional scope model of rumination posits
      that rumination is related to a narrowed attentional scope, which may affect
      processing of neutral and emotional information. This study (n = 56) aimed to
      extend research on the relation between rumination and attentional scope while
      processing neutral, positive, and negative information. To assess attentional
      scope, a moving window task was applied which involved reading both neutral and
      emotional sentences. The result of reading rate indicated that individuals with
      higher levels of trait rumination showed a narrower attentional scope in general.
      In addition, the total reading time of individuals with higher levels of trait
      rumination was shorter when processing neutral and positive sentences through a
      constrained window frame, but this was not the case when processing negative
      sentences. These findings suggest that even though high trait ruminators use an
      overall constrained manner of processing, they may still process negative
      information differently compared to other types of information. (PsycINFO
      Database Record

PMID- 30234328
TI  - To reappraise or not to reappraise? Emotion regulation choice and cognitive
      energetics.
AB  - Research shows that cognitive reappraisal is an effective emotion regulation (ER)
      strategy that often has clear benefits. Yet, surprisingly, recent findings
      demonstrate that people use cognitive reappraisal less frequently than might be
      expected (Suri, Whittaker, & Gross, 2015). We employ cognitive energetics theory
      (CET) to explain this puzzling behavior. CET posits that the likelihood of
      launching any cognitive process is a function of two opposing forces: the driving
      force (i.e., the motivation to launch the process) and the restraining force
      (i.e., task difficulty). We thus hypothesized that people choose to use cognitive
      reappraisal relatively rarely because of the difficulty of implementing it. We
      also postulated that the decision to reappraise (or not) does not simply depend
      on stimuli emotional intensity because the latter is associated with both the
      driving and the restraining forces. In support of our hypotheses, we found that
      when the images' emotional intensity posed difficulty for reappraisal (i.e.,
      highly intense images), reducing this difficulty by asking participants to merely
      predict others' (Study 1) or their own choices (Study 2) increased reappraisal
      choice. Finally, in Study 3, we show that a relatively easy to implement
      reappraisal strategy was chosen more often than the more difficult one for high
      (but not low) intensity images. These findings illustrate the relevance of a CET
      based motivational analysis to emotion regulation choice. (PsycINFO Database
      Record

PMID- 30234329
TI  - Parent-child attachment and children's experience and regulation of emotion: A
      meta-analytic review.
AB  - Attachment relationships serve as contexts within which children develop
      emotional capacities. This meta-analytic review assessed the strength of
      associations of parent-child attachment patterns with the experience and
      regulation of emotion in children under age 18 years. In a series of meta
      analyses (k = 72 studies, N's ranged from 87 to 9,167), we examined children's
      positive and negative affective experiences (assessed either globally or elicited
      in specific contexts), emotion regulation ability, and coping strategies. More
      securely attached children experienced more global positive affect and less
      global negative affect, expressed less elicited negative affect, were better able
      to regulate emotions, and more often used cognitive and social support coping
      strategies. More avoidantly attached children experienced less global positive
      affect, were less able to regulate emotions, and were less likely to use
      cognitive or social support coping strategies. By contrast, more ambivalently
      attached children experienced more global and more elicited negative affect, and
      were less able to regulate emotions. More disorganized children experienced less
      global positive affect and more global negative affect. These robust findings
      provide evidence that attachments to parents have implications for children's
      emotional development, although more research is needed on whether insecure
      attachment patterns are associated with distinct emotion profiles. (PsycINFO
      Database Record

PMID- 30234330
TI  - You look pretty happy: Attractiveness moderates emotion perception.
AB  - A happy face advantage has consistently been shown in emotion categorization
      tasks; happy faces are categorized as happy faster than angry faces as angry.
      Furthermore, social category cues, such as facial sex and race, moderate the
      happy face advantage in evaluatively congruent ways with a larger happy face
      advantage for more positively evaluated faces. We investigated whether
      attractiveness, a facial attribute unrelated to more defined social categories,
      would moderate the happy face advantage consistent with the evaluative congruence
      account. A larger happy face advantage for the more positively evaluated
      attractive faces than for unattractive faces was predicted. Across 4 experiments
      participants categorized attractive and unattractive faces as happy or angry as
      quickly and accurately as possible. As predicted, when female faces were
      categorized separately, a happy face advantage emerged for the attractive females
      but not for the unattractive females. Corresponding results were only found in
      the error rates for male faces. This pattern was confirmed when female and male
      faces were categorized together, indicating that attractiveness may have a
      stronger influence on emotion perception for female faces. Attractiveness is
      shown to moderate emotion perception in line with the evaluative congruence
      account and is suggested to have a stronger influence on emotion perception than
      facial sex cues in contexts where attractiveness is a salient evaluative
      dimension. (PsycINFO Database Record

PMID- 30234331
TI  - Intergenerational transmission of maternal emotion regulation to child emotion
      regulation: Moderated mediation of maternal positive and negative emotions.
AB  - Research on maternal socialization of child emotion regulation often involves
      measures of general parenting, yet little research has considered how maternal
      emotion regulation and emotion expressivity relate to children's ability to
      regulate their emotions. Because emotion regulation can be viewed as
      intergenerational, mothers who display higher levels of positive emotions and
      lower levels of negative emotions may create a more optimal emotional climate for
      children to learn and practice emotion regulation, aiding in the
      intergenerational transmission of optimal emotion regulation. We tested a
      mediation model where maternal positive expressivity was hypothesized to mediate
      the relation of maternal emotion regulation to child emotion regulation. We also
      examined maternal negative expressivity as a moderator of the association of
      maternal positive expressivity to child emotion regulation. Maternal emotion
      regulation, measured as the use of reappraisal, and maternal expressivity were
      self-reported when children were 4-5 years old (T1). Child emotion regulation,
      measured as effortful control, was observed at T1. When children were 8-9 years
      old (T2), a summary score of child emotion regulation was computed from observed
      and teacher-reported effortful control. Higher levels of maternal reappraisal
      were related to more maternal positive expressivity, which in turn was associated
      with better child emotion regulation (T2), controlling for prior levels of child
      regulation (T1), only when maternal negative expressivity was low. This
      longitudinal moderated mediation pathway suggests that adaptive emotion
      regulation strategies used by mothers can be transmitted to children through
      maternal emotional expressions, specifically the interplay of positive and
      negative emotions. (PsycINFO Database Record

PMID- 30234332
TI  - Suppressing but not intensifying emotion decreases arousal and subjective sense
      of recollection.
AB  - Emotional memories are commonly recalled with an increased subjective sense of
      recollection but not necessarily with more accurate context recollection,
      depending on the type of context. Response-focused emotion regulation techniques,
      such as suppressing and intensifying emotion expression, can alter subjective
      arousal and later memory and confidence about memory. Here, we investigated if
      emotion suppression affects later subjective sense of recollection as well as
      context recollection for different types of details. To disentangle the
      contribution of arousal modulation versus potential cognitive costs of emotion
      suppression effects on later subjective sense of recollection, we further
      explored if intensifying emotion expression similarly affects later subjective
      sense of recollection and actual context recollection as emotion suppression. We
      found that emotion suppression decreases the subjective sense of recollection,
      while intensifying emotion expression has no effect on the subjective sense of
      recollection. In contrast, suppressing emotion did not affect the recollection of
      extrinsic and intrinsic contextual details, while intensifying emotion expression
      decreased recollection of intrinsic item features of emotional scenes. In
      conclusion, response-focused emotion regulation techniques with distinct effects
      on subjective arousal differentially affect the subjective sense of recollection
      and memory for contextual details. (PsycINFO Database Record

PMID- 30234333
TI  - Ghosts in the nursery: An experimental investigation of a parent's own
      maltreatment experience, attention to infant faces, and dyadic reciprocity.
AB  - Previous studies have shown that the experience of childhood maltreatment can
      influence recognition and processing of emotional cues and that these effects can
      extend into adulthood. Such alterations in cognitive processing may have
      important implications for processing of infant affect and parenting behavior.
      This study investigated whether the experience of childhood maltreatment altered
      attentional processing of infant faces in a community sample of mothers, using an
      established visual search task. Increased scores on a measure of childhood
      maltreatment were associated with decreased preferential bias toward infant faces
      (indexed by slower reaction times to infant compared to adult faces). Exploratory
      analysis of the relationship between attentional processing and actual "own
      child" parenting behavior (as measured by a video-recorded mother-child
      interaction) found that lower attentional bias to infant faces mediated the
      relationship between higher levels of childhood maltreatment and lower levels of
      mother-infant Dyadic Reciprocity. This suggests that childhood maltreatment may
      have enduring effects on the preferential processing of infant cues as well as
      parenting behavior. (PsycINFO Database Record

PMID- 30234334
TI  - Do positive illusions of control foster happiness?
AB  - Positive emotions have been shown to benefit from optimistic perceptions, even if
      these perceptions are illusory (Seligman & Csikszentmihalyi, 2000). The current
      research investigated the effects of increases and decreases in illusory control
      on positive and negative emotions. In two studies we experimentally induced
      changes in illusory perceptions of control (increase vs. decrease of illusory
      control) and assessed the extent to which these changes, in turn, influenced
      participants' emotions. Extending prior research, the results of both studies
      revealed that whereas illusions of personal control over environmental outcomes
      mitigated the experience of negative emotions, they did not foster positive
      emotions. Perceiving a loss of illusory control, however, significantly reduced
      the experience of positive emotions, but had no effect on negative emotions.
      Implications for emotion theory and intervention programs are discussed.
      (PsycINFO Database Record

PMID- 30234335
TI  - Actions speak louder than gestures when you are 2 years old.
AB  - Interpreting iconic gestures can be challenging for children. Here, we explore
      the features and functions of iconic gestures that make them more challenging for
      young children to interpret than instrumental actions. In Study 1, we show that
      2.5-year-olds are able to glean size information from handshape in a simple
      gesture, although their performance is significantly worse than 4-year-olds'.
      Studies 2 to 4 explore the boundary conditions of 2.5-year-olds' gesture
      understanding. In Study 2, 2.5-year-old children have an easier time interpreting
      size information in hands that reach than in hands that gesture. In Study 3, we
      tease apart the perceptual features and functional objectives of reaches and
      gestures. We created a context in which an action has the perceptual features of
      a reach (extending the hand toward an object) but serves the function of a
      gesture (the object is behind a barrier and not obtainable; the hand thus
      functions to represent, rather than reach for, the object). In this context,
      children struggle to interpret size information in the hand, suggesting that
      gesture's representational function (rather than its perceptual features) is what
      makes it hard for young children to interpret. A distance control (Study 4) in
      which a person holds a box in gesture space (close to the body) demonstrates that
      children's difficulty interpreting static gesture cannot be attributed to the
      physical distance between a gesture and its referent. Together, these studies
      provide evidence that children's struggle to interpret iconic gesture may stem
      from its status as representational action. (PsycINFO Database Record

PMID- 30234336
TI  - Spatial metaphor and the development of cross-domain mappings in early childhood.
AB  - Spatial language is often used metaphorically to describe other domains,
      including time (long sound) and pitch (high sound). How does experience with
      these metaphors shape the ability to associate space with other domains? Here, we
      tested 3- to 6-year-old English-speaking children and adults with a cross-domain
      matching task. We probed cross-domain relations that are expressed in English
      metaphors for time and pitch (length-time and height-pitch) as well as relations
      that are unconventional in English but expressed in other languages (size-time
      and thickness-pitch). Participants were tested with a perceptual matching task,
      in which they matched between spatial stimuli and sounds of different durations
      or pitches, and a linguistic matching task, in which they matched between a label
      denoting a spatial attribute, duration, or pitch and a picture or sound
      representing another dimension. Contrary to previous claims that experience with
      linguistic metaphors is necessary for children to make cross-domain mappings,
      children performed above chance for both familiar and unfamiliar relations in
      both tasks, as did adults. Children's performance was also better when a label
      was provided for one of the dimensions, but only when making length-time, size
      time, and height-pitch mappings (not thickness-pitch mappings). These findings
      suggest that although experience with metaphorical language is not necessary to
      make cross-domain mappings, labels can promote these mappings, both when they
      have familiar metaphorical uses (e.g., English long denotes both length and
      duration) and when they describe dimensions that share a common ordinal reference
      frame (e.g., size and duration but not thickness and pitch). (PsycINFO Database
      Record

PMID- 30234337
TI  - Achieving abstraction: Generating far analogies promotes relational reasoning in
      children.
AB  - Analogical reasoning is essential for transfer by supporting recognition of
      relational similarity. However, not all analogies are created equal. The source
      and target can be similar (near), or quite different (far). Previous research
      suggests that close comparisons facilitate children's relational abstraction. On
      the other hand, evidence from adults indicates that the process of solving far
      analogies may be a more effective scaffold for transfer of a relational strategy.
      We explore whether engaging with far analogies similarly induces such a strategy
      in preschoolers. Children were provided with the opportunity to solve either a
      near or far spatial analogy using a pair of puzzle boxes that varied in
      perceptual similarity (Experiment 1), or to participate in a control task
      (Experiment 2). All groups were then presented with an ambiguous spatial
      reasoning task featuring both object and relational matches. We were interested
      in the relationship between near and far conditions and two effects: (a)
      children's tendency to spontaneously draw an analogy when solving the initial
      puzzle, and (b) their tendency to privilege relational matches over object
      matches in a subsequent, ambiguous task. Although children were more likely to
      spontaneously draw an analogy in the near condition, those who attempted the far
      analogy were more likely to privilege a relational match on the subsequent task.
      We argue that the process of solving a far analogy-regardless of a learner's
      spontaneous success in identifying the relation-contextualizes an otherwise
      ambiguous learning problem, making it easier for children to access and apply
      relational hypotheses. (PsycINFO Database Record

PMID- 30234338
TI  - Violent video games, externalizing behavior, and prosocial behavior: A five-year
      longitudinal study during adolescence.
AB  - Decades of research on the effects of media violence have examined associations
      between viewing aggressive material in the media and aggression and prosocial
      behavior. However, the existing longitudinal studies have tended to exclusively
      examine aggression and prosocial behavior as outcomes, with a limited range of
      potential mediators. The current study examines associations between playing
      violent video games and externalizing and prosocial behavior over a 5-year period
      across adolescence. Additionally, the study examines potential mediators of these
      associations, including empathic concern, benevolence, and self-regulation.
      Participants included 488 adolescents (Mage of child at Wave 1 = 13.83, SD =
      0.98) and their parents, who completed self- and parental measures at three
      different time points, each 2 years apart. Results revealed that early exposure
      to video game violence was indirectly associated with lower levels of prosocial
      behavior as mediated by lower levels of benevolence. Additionally, early video
      game violence play was associated with higher levels of externalizing behavior at
      the cross-sectional level, but not 5 years later. Implications of results for
      adolescents and parents are discussed. (PsycINFO Database Record

PMID- 30234340
TI  - Italian gay father families formed by surrogacy: Parenting, stigmatization, and
      children's psychological adjustment.
AB  - Forty Italian gay father families formed by surrogacy were compared with 40
      Italian lesbian mother families formed by donor insemination, all with a child
      aged 3 to 9 years. Standardized interview, observational, and questionnaire
      measures of parenting quality, parent-child relationships, stigmatization, and
      children's adjustment were administered to parents, children, teachers, and a
      child psychiatrist. The only differences across family types indicated higher
      levels of stigmatization as reported by gay fathers. Externalizing and
      internalizing problems in both groups scored within the normal range. When family
      structure and processes were entered together as predictors of child adjustment,
      a hierarchical linear model analysis showed that factors associated with
      children's externalizing problems were the child's male gender, high
      stigmatization, and negative parenting; children's internalizing problems were
      higher in lesbian mother families and were predicted by stigmatization. Of note,
      neither gay fathers nor lesbian mothers tended to underestimate their children's
      adjustment problems relative to teachers. Finally, for children of gay fathers,
      comparison between teacher SDQ ratings and teacher SDQ normative data on Italian
      children in a similar age range showed that teachers reported children of gay
      fathers to show significantly fewer internalizing problems than the normative
      sample. No differences in children's externalizing problems emerged. A
      bootstrapping simulation confirmed all results, except the effect of
      stigmatization on child internalizing problems. Findings suggest that the
      practice of surrogacy by gay men has no adverse effects on child health outcomes.
      Implications for our theoretical understanding of child socialization and
      development, and law and social policy, are discussed. (PsycINFO Database Record

PMID- 30234339
TI  - Parental acceptance-rejection and child prosocial behavior: Developmental
      transactions across the transition to adolescence in nine countries, mothers and
      fathers, and girls and boys.
AB  - Promoting children's prosocial behavior is a goal for parents, healthcare
      professionals, and nations. Does positive parenting promote later child prosocial
      behavior, or do children who are more prosocial elicit more positive parenting
      later, or both? Relations between parenting and prosocial behavior have to date
      been studied only in a narrow band of countries, mostly with mothers and not
      fathers, and child gender has infrequently been explored as a moderator of
      parenting-prosocial relations. This cross-national study uses 1,178 families
      (mothers, fathers, and children) from 9 countries to explore developmental
      transactions between parental acceptance-rejection and girls' and boys' prosocial
      behavior across 3 waves (child ages 9 to 12). Controlling for stability across
      waves, within-wave relations, and parental age and education, higher parental
      acceptance predicted increased child prosocial behavior from age 9 to 10 and from
      age 10 to 12. Higher age 9 child prosocial behavior also predicted increased
      parental acceptance from age 9 to 10. These transactional paths were invariant
      across 9 countries, mothers and fathers, and girls and boys. Parental acceptance
      increases child prosocial behaviors later, but child prosocial behaviors are not
      effective at increasing parental acceptance in the transition to adolescence.
      This study identifies widely applicable socialization processes across countries,
      mothers and fathers, and girls and boys. (PsycINFO Database Record

PMID- 30234341
TI  - Maternal sensitivity during the first 31/2 years of life predicts
      electrophysiological responding to and cognitive appraisals of infant crying at
      midlife.
AB  - This study examined the predictive significance of maternal sensitivity in early
      childhood for electrophysiological responding to and cognitive appraisals of
      infant crying at midlife in a sample of 73 adults (age = 39 years; 43 females; 58
      parents) from the Minnesota Longitudinal Study of Risk and Adaptation. When
      listening to an infant crying, both parents and nonparents who had experienced
      higher levels of maternal sensitivity in early childhood (between 3 and 42 months
      of age) exhibited larger changes from rest toward greater relative left (vs.
      right) frontal EEG activation, reflecting an approach-oriented response to
      distress. Parents who had experienced greater maternal sensitivity in early
      childhood also made fewer negative causal attributions about the infant's crying;
      the association between sensitivity and attributions for infant crying was
      nonsignificant for nonparents. The current findings demonstrate that experiencing
      maternal sensitivity during the first 31/2 years of life has long-term predictive
      significance for adults' processing of infant distress signals more than three
      decades later. (PsycINFO Database Record

PMID- 30234343
TI  - The anger-depression connection: Between-persons and within-person associations
      from late adolescence to midlife.
AB  - Six waves of data from 944 Canadian high school seniors surveyed for 25 years
      (age 18 to 43) were analyzed to compare three models of the temporal associations
      between expressed anger and depressive symptoms (anger->depression; depression
      >anger; anger<->depression) and a between-persons differences only model (?anger
      = ?depression). Perceived availability of social support was examined as a
      mediator of the anger-depression association. Random intercept cross-lagged panel
      analyses supported the between-persons differences only model, controlling for
      sociodemographic variables, within-time covariances between construct residuals,
      and autoregressive stabilities: Individuals who were higher on expressed anger
      tended to be higher on depressive symptoms and, within individuals, neither
      fluctuations in anger nor depression appeared to influence the other across
      intervals ranging from one year to 18 years. Although social support did not
      mediate an anger-depression connection, intraindividual increases in expressed
      anger predicted future intraindividual increases in perceived support (i.e., age
      18 anger to age 19 support, and age 20 anger to age 22 support). A similar path
      from age 19 depressive symptoms to age 20 perceived support was observed. There
      were also some gender differences in the paths. The results point to stable
      interindividual differences in negative emotionality in place by age 18 and
      maintained up to age 43. (PsycINFO Database Record

PMID- 30234344
TI  - Finding what fits: Breadth of participation at the transition to high school
      mitigates declines in self-concept.
AB  - Extracurricular activities represent a key setting for prevention and promoting
      positive youth development. However, to date, a crucial aspect of activity
      participation-activity breadth (participation in a variety of extracurricular
      settings)-has been largely overlooked as a resource for bolstering adolescents'
      long-term adjustment, especially the development of self-concept. To examine the
      long-term psychosocial effects of involvement in multiple extracurricular
      settings, this study modeled latent trajectories of general, social, and academic
      self-concept and intensity and breadth of participation across 5 years (Grades 8
      12) for 1,146 Australian youth (55% female; agewave 1 12-14). We investigated
      multivariate change in self-concept and breadth of participation, while
      concurrently modeling intensity of participation. Self-concept and breadth
      followed a quadratic trajectory, declining across the early to-middle high school
      years and increasing during the final high school years. Intensity was also
      quadratic, but increased early on, followed by steep declines. Notably (and
      controlling for intensity), wider breadth of participation at the transition to
      high school predicted less-steep declines in general and academic self-concept
      across the early to-middle high school years. Findings support the potential for
      breadth of participation as a promising avenue for stimulating adolescents'
      adjustment by buffering against early declines in their views of self. (PsycINFO
      Database Record

PMID- 30234345
TI  - The codevelopment of community involvement and generative concern pathways in
      emerging and young adulthood.
AB  - In this longitudinal Canadian study, we investigated the relationship between the
      developmental trajectories of community involvement and generative concern
      measured at ages 23, 26, and 32. Participants completed a questionnaire on youth
      involvement, the Youth Involvement Inventory (YII), and the Loyola Generativity
      Scale (LGS) at all 3 ages. A latent growth model (LGM) of community involvement
      predicting time-specific variance in the LGS revealed that: (a) higher levels of
      community involvement at age 23 predicted greater generative concern at ages 23
      and 26, but not at age 32; (b) there were 3 specific indirect paths linking age
      23 community involvement to age 32 generativity through earlier assessments of
      age 23 and age 26 generative concern; and finally (c) a more positive slope of
      community involvement over time predicted higher levels of generative concern at
      age 32. These findings suggest that early involvement in community commitments,
      and increases in community involvement across emerging adulthood, may lead
      individuals down a path toward a more generative personality in young adulthood.
      (PsycINFO Database Record

PMID- 30234342
TI  - Genetic and environmental influences on internalizing psychopathology across age
      and pubertal development.
AB  - Symptoms of anxiety and depression are commonly comorbid and partially share a
      genetic etiology. Mean levels of anxiety and depression increase over the
      transition to adolescence, particularly in girls, suggesting a possible role of
      pubertal development in the activation of underlying genetic risks. The current
      study examined how genetic and environmental influences on anxiety and depression
      differed by chronological age and pubertal status. We analyzed composite scores
      from child self-reports and parent informant-reports of internalizing
      symptomology in a racially and socioeconomically diverse sample of 1,913
      individual twins from 1,006 pairs (ages 8-20 years) from the Texas Twin Project.
      Biometric models tested age and pubertal status as moderators of genetic and
      environmental influences shared between and specific to anxiety and depression to
      determine whether etiology of internalizing symptomology differs across
      development as a function of age or puberty. Genetic influences did not increase
      as a function of age or puberty, but instead shared environmental effects
      decreased with age. In an exploratory model that considered the moderators
      simultaneously, developmental differences in etiology were reflected in genetic
      and environmental effects unique to depression. Results suggest that genetic
      variance in internalizing problems is relatively constant during adolescence,
      with environmental influences more varied across development. (PsycINFO Database
      Record

PMID- 30234346
TI  - From science student to scientist: Predictors and outcomes of heterogeneous
      science identity trajectories in college.
AB  - This 5-year longitudinal study investigates the development of science identity
      throughout college from an expectancy-value perspective. Specifically,
      heterogeneous developmental patterns of science identity across 4 years of
      college were examined using growth-mixture modeling. Gender, race/ethnicity, and
      competence beliefs (efficacy for science tasks, perceived competence in science)
      were modeled as antecedents, and participation in a science career after
      graduation was modeled as a distal outcome of these identity development
      trajectories. Three latent classes (High with Transitory Incline, Moderate-High
      and Stable, and Moderate-Low with Early Decline) were identified. Gender,
      race/ethnicity, and competence beliefs in the first year of college significantly
      predicted latent class membership. In addition, students in the two highest
      classes were significantly more likely to report being involved in science
      careers or science fields after college graduation than students in the Moderate
      Low with Early Decline class. (PsycINFO Database Record

PMID- 30234347
TI  - Discrimination, segregation, and chronic inflammation: Testing the weathering
      explanation for the poor health of Black Americans.
AB  - Several studies have reported a relation between race-related stressors and the
      poor health of Black Americans. Such findings raise questions regarding the
      mediating biological mechanisms that might account for this link. The present
      study investigated elevated systemic inflammation, a factor shown to be a strong
      predictor of chronic illness and mortality in all ethnic populations, as a
      possible factor. Using 7 waves of data from the Family and Community Health
      Study, collected over a 20-year period from over 400 Black Americans, we
      investigated the extent to which exposure to discrimination and segregation at
      various points in the life course predicted adult inflammation at age 28. Our
      analyses examined whether cumulative stress, stress generation, or predictive
      adaptive response (PAR) models best accounted for any associations that existed
      between these race-related stressors and adult inflammation. At every wave of
      data collection, assessments of discrimination and segregation were related to
      adult inflammation. However, multivariate analyses using structure equation
      modeling indicated that the PAR model best explained the effect of these race
      related stressors on inflammation. Exposure to discrimination and segregation
      during the juvenile years predicted adult inflammation and amplified the
      inflammatory effect of adult exposure to these race-related stressors. These
      effects were considerably more robust than that of traditional health risk
      factors such as diet, exercise, smoking, and low SES. Implications of these
      findings are discussed, including the limitations of the widely accepted risk
      factor approach to increasing the health of Black Americans. (PsycINFO Database
      Record

PMID- 30234348
TI  - Physical activity and health-related quality of life in children and adolescents:
      A systematic review and meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to quantify the effect of physical
      activity (in both descriptive and intervention studies) on health-related quality
      of life (HRQOL) in children and adolescents from both healthy and chronic illness
      populations. METHOD: A systematic review of PubMed, PsycINFO, and ProQuest
      identified 33 studies of physical activity and HRQOL in youth, including
      descriptive and prepost intervention designs. RESULTS: In descriptive studies (N
      = 14), there was a small, positive association between physical activity and
      HRQOL based on child-reports (Hedges' g = .302, p < .001, 95% confidence
      interval, CI [.178, .426]) and a negligible association based on parent-proxy
      reports (Hedges' g = .115, p = .101, 95% CI [-.023, .253]). Intervention studies
      (N = 19) yielded a small, positive effect of physical activity intervention on
      HRQOL based on child-reports (Hedges' g = .279, p = .014, 95% CI [.057, .500])
      and a medium, positive effect based on parent-proxy reports (Hedges' g = .522, p
      = .012, 95% CI [.117, .928]). Intervention effects were attenuated by removal of
      a single study. Hypothesized and exploratory moderators did not moderate the
      relationship between physical activity and HRQOL. CONCLUSIONS: Findings supported
      the primary hypothesis that physical activity was related to better HRQOL in
      youth, although the magnitude of these effects did not represent a minimal
      clinically important difference (MCID) in most studies. Future studies are needed
      to assess HRQOL in youth before and after exercise interventions to quantify the
      type, frequency, duration, and intensity of physical activity needed to change
      HRQOL. (PsycINFO Database Record

PMID- 30234349
TI  - Relationships among affective states, physical activity, and sedentary behavior
      in children: Moderation by perceived stress.
AB  - OBJECTIVE: We examined the acute bidirectional relationships between affective
      states and moderate-to-vigorous physical activity (MVPA) or sedentary behavior
      (SB) in children, and whether perceived stress moderates these associations.
      METHOD: A total of 180 children (mean age = 9.6 years, 51.7% female, 53.9%
      Hispanic) completed a 7-day ecological momentary assessment (EMA) study, where
      they received 3-7 random prompts per day asking about their current affective
      states. MVPA and SB during this period were measured by waist-worn
      accelerometers. Children's and mothers' perceived stress were measured by paper
      questionnaires. Multilevel models tested the within-person (WP) and between
      person (BP) associations of (a) MVPA and SB 30 and 60 min before an EMA prompt
      with subsequent affective states at the prompt, and (b) affective states at the
      prompt with MVPA and SB in the subsequent 30 and 60 min after the prompt.
      Interaction terms were used to assess whether children's and mothers' perceived
      stress moderated these associations. RESULTS: Children reported a higher positive
      affect after engaging in more MVPA than usual (WP; beta = 0.04, SE = 0.02, p <
      .05) and a lower positive affect after spending more SB than usual (WP; beta = 
      0.02, SE = 0.01, p < .05) in the previous 30 min. Children's affective states
      were unrelated to time in MVPA and SB within the subsequent 30 min. Parent's
      perceived stress level attenuated the relationship between children's time spent
      in MVPA 60 min before a prompt and self-reported positive affect at that prompt
      (beta = -0.01, SE = 0.01, p < .05). CONCLUSIONS: MVPA and SB acutely impacted
      children's psychological well-being, with the benefits of MVPA on positive affect
      across longer intervals attenuated among children whose mothers had higher
      perceived stress. (PsycINFO Database Record

PMID- 30234350
TI  - Affective response during physical activity: Within-subject differences across
      phases of behavior change.
AB  - OBJECTIVE: Affective response during physical activity may be a key factor
      reinforcing future behavior. However, little is known about how affective
      responses during physical activity may differ across phases of behavior change.
      This study used real-time Ecological Momentary Assessment (EMA) to examine within
      subject differences in affective response during physical activity in daily life
      as individuals transitioned across phases of behavior change. METHOD: A sample of
      115 adults (M = 41.0 years, 74% female) participated in an intensive longitudinal
      study with measurement bursts at 0, 6, and 12-months. Each burst consisted of 8
      randomly-prompted EMA occasions per day across 4 days. EMA self-report items
      assessed current activity level (i.e., physical activity or nonphysical
      activity), and positive and negative affect. Questionnaires measured phase of
      behavior change (e.g., preaction [no regular physical activity], action [regular
      physical activity <6 months], and maintenance [regular physical activity >=6
      months]) at each burst. Three-level (Level-1 = occasion, Level-2 = burst, Level-3
      = person) linear regression models tested Phase of Change (Level-2, within
      subject) * Physical Activity Level (Level-1, within-subject) interactions
      controlling for day of week, time of day, and sex. RESULTS: Positive affective
      response during physical activity (vs. nonphysical activity) was higher when
      individuals were in preaction phases (vs. action). Negative affective response
      during physical activity (vs. nonphysical activity) was lower when individuals
      were in the maintenance phase (vs. action). CONCLUSIONS: Long-term maintenance of
      physical activity may be particularly challenging, given the lack of positive
      reinforcement that is thought to be needed to sustain behavior. (PsycINFO
      Database Record

PMID- 30234351
TI  - Mindfulness meditation and physical activity: Evidence from 2012 National Health
      Interview Survey.
AB  - OBJECTIVE: Physical activity is critical for health, yet only about half of the
      U.S. adult population meets basic aerobic physical activity recommendations and
      almost a third are inactive. Mindfulness meditation is gaining attention for its
      potential to facilitate health-promoting behavior and may address some
      limitations of existing interventions for physical activity. However, little
      evidence exists on mindfulness meditation and physical activity. This study
      assessed whether mindfulness meditation is uniquely associated with physical
      activity in a nationally representative sample. METHOD: Cross-sectional data from
      the adult sample (N = 34,525) of the 2012 National Health Interview Survey were
      analyzed. Logistic regression models tested whether past-year use of mindfulness
      meditation was associated with (a) inactivity and (b) meeting aerobic physical
      activity recommendations, after accounting for sociodemographics, another health
      promoting behavior, and 2 other types of meditation. Data were weighted to
      represent the U.S. civilian, noninstitutionalized adult population. RESULTS:
      Accounting for covariates, U.S. adults who practiced mindfulness meditation in
      the past year were less likely to be inactive and more likely to meet physical
      activity recommendations. Mindfulness meditation showed stronger associations
      with these indices of physical activity than the 2 other types of meditation.
      CONCLUSIONS: These results suggest that mindfulness meditation specifically,
      beyond meditation in general, is associated with physical activity in U.S adults.
      Future research should test whether intervening with mindfulness meditation
      either as an adjunctive component or on its own-helps to increase or maintain
      physical activity. (PsycINFO Database Record

PMID- 30234352
TI  - Development of a lifestyle intervention for the metabolic syndrome: Discovery
      through proof-of-concept.
AB  - OBJECTIVE: The aim was to describe the early phases of the progressive
      development of a lifestyle treatment for sustained remission of the metabolic
      syndrome (MetS) using the Obesity-Related Behavioral Intervention Trials (ORBIT)
      model for behavioral treatment development as a guide. METHODS: Early discovery
      and design phases produced a 3-component (diet, physical activity, stress), group
      based lifestyle treatment with an intensive 6-month phase followed by monthly,
      participant-led maintenance meetings. In the proof-of-concept phase, 26
      participants with the MetS (age 53 +/- 7 years, 77% female, and 65% ethnic
      minority) were recruited in a quasi-experimental design to determine if treatment
      could achieve the prespecified benchmark of MetS remission in >=50% at 2.5 years.
      Exploratory outcomes focused on MetS components, weight, and patient-centered
      benefits on energy/vitality and psychosocial status. RESULTS: MetS remission was
      achieved in 53.8% after a median of 2.5 years. At 2.5 years, an increase of
      +15.4% reported eating >=3 servings of vegetables/day, +7.7% engaged in >=150
      minutes of moderate-to-vigorous physical activity/week; and +11.5% reported
      experiencing no depression in the past 2 weeks. Weight loss >=5% was achieved by
      38.5%, and energy/vitality, negative affect, and social support improved. Median
      group attendance over 2.5 years was 73.8%. CONCLUSIONS: It is plausible that this
      lifestyle program can produce a remission in the MetS, sustained through 2.5
      years. After refinements to enhance precision and strength, progression to
      feasibility pilot testing and a randomized clinical trial will determine its
      efficacy as a cost-effective lifestyle option for managing the MetS in the
      current health care system. (PsycINFO Database Record

PMID- 30234353
TI  - Self-perceived overweight, weight loss attempts, and weight gain: Evidence from
      two large, longitudinal cohorts.
AB  - OBJECTIVE: Self-identification of overweight is associated with a greater desire
      to lose weight, but also counterintuitively with increased future weight gain.
      The present research examined whether weight loss attempts mediate the
      prospective relation between self-perceived weight status and weight gain across
      adolescence and young adulthood. METHOD: Data from 2 longitudinal cohort studies
      was used. Study 1 tested whether the association between self-perceived weight
      status and weight gain (from age 10/11-14/15 years) was mediated by weight loss
      attempts among Australian adolescents. Study 2 focused on young adults based in
      the United States and examined whether attempts at weight loss mediated the
      relation between self-perceived overweight and weight gain from ages 16 to 28
      years. RESULTS: In Study 1, self-perceived weight status among adolescents was
      associated with greater weight gain and weight loss attempts mediated 16% of this
      relation. In Study 2, young adults who perceived their weight status as
      overweight gained more weight over time and weight loss attempts mediated 27% of
      this relation. CONCLUSIONS: Adolescents and young adults that identify they are
      overweight are more likely to gain weight over time and weight loss attempts
      appear to mediate this effect. (PsycINFO Database Record

PMID- 30234354
TI  - How cohabitation, marriage, separation, and divorce influence BMI: A prospective
      panel study.
AB  - OBJECTIVE: This study examines how changes in cohabitation or marital status
      affect Body Mass Index (BMI) over time in a large representative sample. METHOD:
      Participants were 20,950 individuals (50% female; 19 to 100 years),
      representative of the German population, who provided 81,926 observations over 16
      years. Face-to-face interviews were used to obtain demographic data, including
      cohabitation and marital status, height, body weight, and weight-relevant
      behaviors (exercise, healthy eating, and smoking). Control variables included
      age, notable changes in status (life events such as having children or change in
      employment status), perceived stress, and subjective health. RESULTS:
      Cohabitation led to significant weight gain in men and women-after four years or
      longer, about twice the gain associated with marriage (controlling for weight
      related behaviors, age, children, employment, stress, and health). BMI after
      separation was largely comparable to BMI before starting cohabitation; women lost
      some weight in the first year, men gained some weight after four or more years of
      separation. Divorce generally predicted weight gain. Changes in exercise, healthy
      eating, and smoking did not attenuate the effect of changes in relationship
      status on BMI. CONCLUSIONS: This is among the first longitudinal studies to
      directly compare the effects of key changes in relationship status on BMI. The
      findings extend and qualify previous results by showing that the benefits of
      marriage or cohabitation do not necessarily include a healthier BMI. They also
      suggest that relationship transitions-particularly moving in with a partner and
      divorce-may be important time windows for weight gain prevention. (PsycINFO
      Database Record

PMID- 30234355
TI  - Longitudinal associations between psychological well-being and the consumption of
      fruits and vegetables.
AB  - BACKGROUND: Psychological well-being is associated with longevity and reduced
      risk of disease, but possible mechanisms are understudied. Health behaviors like
      eating fruits and vegetables may link psychological well-being with better
      health; however, most evidence is cross-sectional. PURPOSE: This study
      investigated psychological well-being's longitudinal association with fruit and
      vegetable consumption across as many as 7 years. METHOD: Participants were 6,565
      older adults from the English Longitudinal Study of Ageing, which includes men
      and women aged 50 years or older. Psychological well-being was assessed with 17
      items from the Control, Autonomy, Satisfaction, Pleasure Scale. Fruit and
      vegetable consumption was initially assessed during 2006-2007 and then
      approximately every 2 years through 2012-2013. Covariates included
      sociodemographic factors, health status, and other health behaviors. RESULTS:
      Mixed linear models showed that higher baseline levels of psychological well
      being were associated with more fruit and vegetable consumption at baseline (beta
      = 0.05, 95% confidence interval [CI] [0.02, 0.08]) and that fruit and vegetable
      consumption declined across time (beta = -0.01, 95% CI [-0.02, -0.004]).
      Psychological well-being interacted significantly with time such that individuals
      with higher baseline psychological well-being had slower declines in fruit and
      vegetable consumption (beta = 0.01, 95% CI [0.01, 0.02]). Among individuals who
      initially met recommendations to consume 5 or more servings of fruits and
      vegetables (N = 1,719), higher baseline psychological well-being was associated
      with 11% reduced risk of falling below recommended levels during follow-up
      (hazard ratio = 0.89, 95% CI [0.83, 0.95]). CONCLUSIONS: Findings suggest that
      psychological well-being may be a precursor to healthy behaviors such as eating a
      diet rich in fruits and vegetables. (PsycINFO Database Record

PMID- 30234357
TI  - Subjective social status and health: A meta-analysis of community and society
      ladders.
AB  - OBJECTIVE: To derive a robust estimate of the relation between health and
      subjective status in society versus subjective status in one's community, and to
      identify moderators of these effects, using meta-analysis. METHOD: Thirty-eight
      independent studies, which included both subjective status ladders and
      collectively provided data from 142,836 participants, met criteria for inclusion.
      Information on sample characteristics (e.g., age, gender, continent),
      methodological factors (e.g., scale type, methodological quality), and
      statistical factors (e.g., model type, inclusion of objective socioeconomic
      status covariates) were extracted from each study. Random-effects meta-analysis
      was used to aggregate data across studies. RESULTS: Both the community ladder and
      the society ladder yielded small but statistically significant associations with
      health behavior (r = .06 and r = .06), mental health (r = .13 and r = .11),
      physical health (r = .05 and r = .04), and self-rated health (r = .08 and r =
      .09) that were comparable in size and were qualified in a similar way by the type
      of health outcome, sample age, continent, and methodological quality.
      Additionally, community and society ladders remained significantly associated
      with health both when considered simultaneously and following the inclusion of
      objective socioeconomic status covariates. CONCLUSIONS: This meta-analysis is the
      first to establish a unique association of the community ladder with health. It
      also supports social comparison theories highlighting the importance of
      comparisons with proximal others and may promote greater use of the community
      ladder in future research. (PsycINFO Database Record

PMID- 30234358
TI  - The role of school psychologists in the support of grieving children.
AB  - School psychologists are in a unique position to both identify and work with
      grieving students; to provide guidance to schools, families, and peers on
      approaches to support such children and youth; and to offer training to classroom
      educators so that they are better prepared to support grieving students. Yet,
      there has been minimal research published on this topic in professional journals.
      This special section of School Psychology Quarterly is devoted to grief and loss
      with the hope of beginning to narrow this gap in the literature. The three
      articles in this special section add to an evolving evidence-base that grief in
      children is common and the impact can be profound, that school professionals can
      and should play a major role in supporting grieving children, and that school
      psychologists can play a key role in empowering classroom educators and other
      school professionals so that no child in the future has to grieve alone.
      (PsycINFO Database Record

PMID- 30234359
TI  - Grief and growth in bereaved siblings: Interactions between different sources of
      social support.
AB  - The objective was to characterize the relation between different sources of
      school-based social support (friends, peers, and teachers) and bereaved siblings'
      grief and grief-related growth and to examine whether nonparental sources of
      social support buffer the effects of low parent support on bereaved siblings.
      Families (N = 85) were recruited from cancer registries at 3 pediatric
      institutions 3-12 months after a child's death. Bereaved siblings were 8-18 years
      old (M = 12.39, SD = 2.65) and majority female (58%) and White (74%). During home
      visits, siblings reported their perceptions of social support from parental and
      nonparental sources using the Social Support Scale for Children, as well as grief
      and grief-related growth using the Hogan Sibling Inventory of Bereavement.
      Parent, friend, and teacher support were positively correlated with grief-related
      growth, whereas parent and peer support were negatively correlated with grief for
      adolescents. Teacher and friend support significantly moderated the association
      between parent support and grief such that teacher and friend support accentuated
      the positive effects of parent support. Friend and peer support moderated
      associations between parent support and grief/growth for adolescents but not
      children. School-based social support, namely from friends, peers, and teachers,
      appears to facilitate the adjustment of bereaved siblings. Findings suggest that
      bereaved siblings may benefit from enhanced support from teachers and friends
      regardless of age, with middle/high school students particularly benefitting from
      increased support from close friends and peers. (PsycINFO Database Record

PMID- 30234356
TI  - Family obligations and asthma in youth: The moderating role of socioeconomic
      status.
AB  - OBJECTIVE: Fulfilling family obligations-providing instrumental help to and
      spending time with family-is a common aspect of family relationships. However,
      whether fulfilling these obligations links with physical health remains unclear.
      In this study, we investigated whether fulfilling family obligations was
      associated with asthma outcomes among youth, and whether these associations
      differed depending on family socioeconomic status (SES). METHOD: Participants
      were 172 youth, 8 to 17 years of age (Mage = 12.1; 54% boys) who had been
      physician-diagnosed with asthma and reported on family-obligation frequency;
      completed the Asthma Control Test (ACT; Nathan et al., 2004), a clinical measure
      of asthma control; and completed a measure of airway inflammation (i.e.,
      fractional exhaled nitric oxide). Parents also completed the ACT in reference to
      their asthmatic children and reported on family income. RESULTS: Fulfilling
      family obligations was not associated with asthma outcomes (betas < .14, ps >
      .075). However, SES (family income) interacted with family obligations, such that
      fulfilling family obligations was associated with greater airway inflammation
      (interaction term beta = -.17, p = .023) and poorer parent-reported asthma
      control (interaction term beta = .15, p = .039), only among youth from lower SES
      backgrounds. Exploratory analyses suggest that these interactions were robust
      against covariates and were largely consistent across age and the two dimensions
      of family-obligation behaviors. CONCLUSION: Findings from this study suggest that
      among youth from lower SES backgrounds, engaging in more frequent family
      obligation behaviors may have negative repercussions in terms of their asthma.
      (PsycINFO Database Record

PMID- 30234360
TI  - Links between bereavement due to sudden death and academic functioning: Results
      from a nationally representative sample of adolescents.
AB  - Bereavement due to sudden loss may disrupt positive adjustment among youth, yet
      few studies have examined the age at which youth are most likely to first
      encounter sudden loss, the co-occurrence of sudden loss with other traumatic
      events, and the independent effects of sudden loss on academic functioning. Data
      were analyzed from the National Comorbidity Survey-Adolescent Supplement (N =
      10,148, Mage = 15.18, 51.1% female). Youth reported on whether they had
      experienced sudden loss (along with 17 other traumatic events), the age at which
      they had first experienced sudden loss, and multiple indicators of academic
      functioning. Sudden loss was the most frequently occurring traumatic event among
      youth; approximately 30% of adolescents reported at least one sudden loss in
      their lifetime. Youth were most likely to have first experienced sudden loss
      during middle adolescence (15 to 16 years of age). Although sudden loss co
      occurred with several other traumas, about 10% of youth reported experiencing
      only sudden loss. After accounting for demographic characteristics and other
      traumatic events, experiencing sudden loss was associated with lower academic
      achievement, lower ability to concentrate and learn, less enjoyment of school,
      lower school belongingness, and lower beliefs that teachers treat youth fairly.
      Sudden loss is common among adolescents and has important implications for school
      functioning. Schools may improve academic functioning by adopting routine
      screening for sudden loss and assessing potential need for bereavement-informed
      mental health services. (PsycINFO Database Record

PMID- 30234361
TI  - Relational teaching and learning after loss: Evidence from Black adolescent male
      students and their teachers.
AB  - Prior research shows that many teachers feel ill-equipped to deal with students
      experiencing loss, and teachers of Black male adolescents, in particular,
      sometimes mistake grieving for misbehavior. This multimethod case study
      investigated the way teachers and their Black male students at a single-sex
      school related around encounters with loss. We examined students' and teachers'
      grief experiences through stories that were shared during qualitative interviews
      and focus group meetings and by observing everyday interactions throughout the
      school building. Additionally, a survey was distributed to the senior class and
      school staff asking respondents to report their experiences with loss, grief, and
      relational support. We found that both groups shared a desire to forge
      relationships for grief support and that both students and teachers also felt
      their emotional needs were unacknowledged at times. We also documented many
      successful moments when the strength of a personal bond between student and
      teacher eased the pain of a significant personal loss. In this article, we argue
      that specific relational strategies, as outlined within the model of relational
      teaching and learning, can be effective for supporting students through periods
      of grief and can, in turn, also positively impacts teachers' own recovery from
      loss. Furthermore, we propose that school psychologists can play a critical role
      in supporting the relationship building between students and teachers,
      particularly in under-resourced schools without enough mental health personnel.
      (PsycINFO Database Record

PMID- 30234362
TI  - Math and science motivation in internationally adopted adolescents.
AB  - Despite prior studies documenting learning difficulties among internationally
      adopted youth (IAY), none has explored academic motivation within this
      population. The current study addressed this gap by examining expectancies for
      success and task values in math and science among internationally adopted,
      domestically adopted, and nonadopted high-school students. Differences in
      students' math achievement and parents' beliefs about their ability were also
      explored. A subsample of 7,420 11th-grade students was selected from the High
      School Longitudinal Study data set (Ingels et al., 2011). After controlling for
      prior motivation, achievement, demographics, and clustering, analyses revealed
      that IAY held less adaptive motivational beliefs in math. Compared with their
      nonadopted peers, internationally adopted students reported lower expectancies
      for success, attainment value, and intrinsic value in math. Few differences in
      science motivation emerged, and no differences in math achievement were observed.
      (PsycINFO Database Record

PMID- 30234363
TI  - Health Disparities in Access to Nonpharmacologic Therapies in an Urban Community.
AB  - OBJECTIVE: The overuse of prescription opioids for chronic pain is recognized as
      a public health crisis. Yet, poor access to nonpharmacologic treatments is the
      norm in low-income, racially and ethnically diverse patients with chronic pain.
      The main objective of this study was to understand how chronic pain impacts low
      income individuals with chronic pain and their communities from multiple
      perspectives. DESIGN: This was a qualitative study using a Science Cafe
      methodology. SETTING: The Science Cafe event was held at an urban community
      center in Boston, MA. SUBJECTS: Inclusion criteria included the following: having
      the ability to attend the event, being at least 18 years of age or older, and
      participating in English. METHODS: Data were collected through self-reported
      questionnaires and audio or video recordings of two focus groups. Quantitative
      and qualitative data were analyzed with SAS 9.3 and NVivo 10. RESULTS: Thirty
      participants attended the Science Cafe event. The average age was 45 years, 77%
      reported as female, 42% identified as black, and 19% as Hispanic. Participants
      identified themselves as either patients (46%) or providers (54%) to the chronic
      pain community. Our forum revealed three major themes: (1) nonpharmacologic
      options for chronic pain management are warranted, (2) larger sociodemographic
      and contextual factors influence management of chronic pain, and (3) both
      patients and providers value the patient-provider relationship and acknowledge
      the need for better communication for patients with chronic pain. CONCLUSIONS:
      Future research should consider identifying and addressing disparities in access
      to nonpharmacologic treatments for chronic pain in relation to underlying social
      determinants of health, particularly for racially and ethnically diverse
      patients.

PMID- 30234364
TI  - Autophagy in Adipose Tissue Physiology and Pathophysiology.
AB  - SIGNIFICANCE: Alterations in adipose tissue function have profound consequences
      on whole body energy homeostasis because this tissue is central for fat
      accumulation, energy expenditure, glucose and insulin metabolism, and hormonal
      regulation. With the obesity reaching epidemic proportions globally, it is
      important to understand the mechanisms leading to adipose tissue malfunction.
      Recent Advances: Autophagy has originally been viewed as an adaptive response to
      cellular stress, but in recent years this process was shown to regulate important
      cellular processes. In adipose tissue, autophagy is a key regulator of white
      adipose tissue (WAT) and brown adipose tissue (BAT) adipogenesis, and
      dysregulated autophagy impairs fat accumulation both in vitro and in vivo. Animal
      studies have also suggested an important role for autophagy and mitophagy during
      the transition from beige to white fat. Human studies have provided evidence for
      altered autophagy in WAT, and these alterations correlated with the degree of
      insulin resistance. CRITICAL ISSUES: Despite these important advances in the
      study of autophagy in adipose tissue, we still do not understand the
      physiological role of autophagy in mature white and brown adipocytes.
      Furthermore, several human studies involving autophagy assessment were performed
      on whole adipose tissue, which complicates the interpretation of the results
      considering the cellular heterogeneity of this tissue. FUTURE DIRECTIONS: Future
      studies will undoubtedly expand our understanding of the role of autophagy in
      fully differentiated adipocytes, and uncover novel cross-talks between this
      tissue and other organs in regulating lipid metabolism, redox signaling, energy
      homeostasis, and insulin sensitivity. Antioxid. Redox Signal. 00, 000-000.

PMID- 30234365
TI  - Predictors of Recent HIV Testing Among Chinese Men Who Have Sex with Men: A
      Barrier Perspective.
AB  - In China, men who have sex with men (MSM) account for an increasing proportion of
      new HIV infections. We aim to assess recent HIV testing (in the past 6 months)
      among Chinese MSM and to identify barriers to testing. A nationwide sample of MSM
      (n = 1100) from mainland China was recruited. Data on sociodemographics, HIV
      related risks, perceived barriers to testing, and testing behaviors were
      collected. Approximately 30% of MSM had recently undergone HIV testing. With
      regard to testing, almost half endorsed each of three barriers: did not believe
      themselves to be at HIV risk, had a fear of being diagnosed HIV positive, and
      feared their privacy would be violated during testing. Five distinct classes of
      barriers were identified from the responses. The adjusted multivariable logistic
      regression model demonstrated that the participants in both the "uncertainty
      concerning testing sites" and "low risk and privacy violation" classes were less
      likely to undergo testing than those in the "minimal barrier" class. Men who were
      unsure of their HIV status were less likely to undergo testing. Furthermore,
      participants who had multiple male sexual partners and who engaged in substance
      use over the preceding 6 months were more likely to undergo testing. Distinct
      subgroups of testing and HIV status varied within the different barrier
      classifications. Recent HIV testing rates remain low among MSM in China. Barrier
      factors associated with testing point to the necessity for preventing and
      controlling HIV, including increasing the privacy of sites or educating MSM on
      the importance of testing regularly.

PMID- 30234366
TI  - Management of Tumor Necrosis Factor alpha Inhibitor Therapy After Renal
      Transplantation: A Comparative Analysis and Associated Outcomes.
AB  - BACKGROUND: Biologic agents inhibiting the tumor necrosis factor alpha pathway
      (TNFalpha-Is) are used to treat systemic inflammatory diseases. The best
      management of these agents after renal transplantation is unknown. OBJECTIVE:
      Evaluate peritransplant use of TNFalpha-Is and associated outcomes. METHODS:
      Retrospective, single-center study of adult renal-transplant-recipients (RTRs)
      transplanted between 1/1/1998-12/31/2017, who received TNFalpha-Is for
      inflammatory disease prior to transplant. Qualifying patients were divided into 2
      cohorts: patients who resumed TNFalpha-Is after transplant and those who did not.
      Outcomes were evaluated. RESULTS: A total of 5256 renal transplants occurred in
      the study window; 14 patients met inclusion criteria. Primary indication for
      TNFalpha-I was Crohn's-disease (CD; 57.1%). Infliximab was utilized most
      frequently (50%). Seven RTRs resumed TNFalpha-I posttransplant; mean time to
      resumption of 10.6+/-4.35 months (median=6 months), 85.7% for CD.
      Immunosuppression was modified in 2 patients (28.6%) in response to restarting
      TNFalpha-I therapy. Seven RTRs did not resume TNFalpha-Is following transplant;
      the majority of these had rheumatic diseases. There was no significant difference
      in time to first bacterial or fungal infection, rejection, or patient survival
      between the 2 groups. Last measured estimated glomerular-filtration-rate was
      similar between groups (TNFalpha-I: 41 +/- 14.2 vs 48.6 +/- 8.6, P = 0.25). No
      patient had cytomegalovirus infection; however, 42.8% of each cohort had
      documented BK virus infection. Malignancy occurred more frequently in the cohort
      that resumed TNFalpha-Is (42.8% vs 14.3%, P = 0.24); however, this was not
      statistically significant. Conclusion and Relevance: TNFalpha-I therapy prior to
      renal-transplant is relatively uncommon. The decision to continue therapy after
      transplant must balance risks of infection and malignancy against inflammatory
      disease recurrence. A multidisciplinary treatment approach is necessary as use of
      TNFalpha-I affects immunosuppressive management and appears to affect transplant
      outcomes. Future studies are needed to further clarify the role of TNFalpha-I
      therapy use in RTRs with inflammatory disorders focusing on its correlation with
      both BK and malignancy.

PMID- 30234367
TI  - The Prevalence and Nature of Medication Errors and Adverse Events Related to
      Preadmission Medications When Patients Are Admitted to an Orthopedic Inpatient
      Unit: An Observational Study.
AB  - BACKGROUND: Medication errors commonly occur when patients move from the
      community into hospital. Whereas medication reconciliation by pharmacists can
      detect errors, delays in undertaking this can increase the risk that patients
      receive incorrect admission medication regimens. Orthopedic patients are an at
      risk group because they are often elderly and use multiple medications.
      OBJECTIVE: To evaluate the prevalence and nature of medication errors when
      patients are admitted to an orthopedic unit where pharmacists routinely undertake
      postprescribing medication reconciliation. METHODS: A 10-week retrospective
      observational study was conducted at a major metropolitan hospital in Australia.
      Medication records of orthopedic inpatients were evaluated to determine the
      number of prescribing and administration errors associated with patients'
      preadmission medications and the number of related adverse events that occurred
      within 72 hours of admission. RESULTS: Preadmission, 198 patients were taking at
      least 1 regular medication, of whom 176 (88.9%) experienced at least 1 medication
      error. The median number of errors per patient was 6 (interquartile range 3-10).
      Unintended omission of a preadmission medication was the most common prescribing
      error (87.4%). There were 17 adverse events involving 24 medications in 16 (8.1%)
      patients that were potentially related to medication errors; 6 events were deemed
      moderate consequence (moderate injury or harm, increased length of stay, or
      cancelled/delayed treatment), and the remainder were minor. Conclusion and
      Relevance: Medication errors were common when orthopedic patients were admitted
      to hospital, despite postprescribing pharmacist medication reconciliation. Some
      of these errors led to patient harm. Interventions that ensure that medications
      are prescribed correctly at admission are required.

PMID- 30234368
TI  - Redox Pioneer: Professor Hideo Kimura.
AB  - Dr. Hideo Kimura is recognized as a redox pioneer because he has published an
      article in the field of antioxidant and redox biology that has been cited >1000
      times, and 29 articles that have been cited >100 times. Since the first
      description of hydrogen sulfide (H2S) as a toxic gas 300 years ago, most studies
      have been devoted to its toxicity. In 1996, Dr. Kimura demonstrated a
      physiological role of H2S as a mediator of cognitive function and cystathionine
      beta-synthase as an H2S-producing enzyme. In the following year, he showed H2S as
      a vascular smooth muscle relaxant in synergy with nitric oxide and its production
      by cystathionine gamma-lyase in vasculature. Subsequently he reported the
      cytoprotective effect of H2S on neurons against oxidative stress. Since then,
      studies on H2S have unveiled numerous physiological roles such as the regulation
      of inflammation, cell growth, oxygen sensing, and senescence. He also discovered
      polysulfides (H2Sn), which have a higher number of sulfur atoms than H2S and are
      one of the active forms of H2S, as potent signaling molecules produced by 3
      mercaptopyruvate sulfurtransferase. H2Sn regulate ion channels and transcription
      factors to upregulate antioxidant genes, tumor suppressors, and protein kinases
      to, in turn, regulate blood pressure. These findings led to the re-evaluation of
      other persulfurated molecules such as cysteine persulfide and glutathione
      persulfide. Dr. Kimura is a pioneer of studies on H2S and H2Sn as signaling
      molecules. It is fortunate to come across a secret of nature and pick it up.   
      Prof. Hideo Kimura.

PMID- 30234369
TI  - Evaluation of Pharmacy-Developed Antibiotic Desensitization Protocols.
AB  - BACKGROUND: Parameters within reconstitution, storage, stability, and
      administration may be optimized according to the unique pharmacokinetics of each
      antibiotic to ensure a successful desensitization. OBJECTIVE: The study aims to
      evaluate the successfulness and safety of antibiotic desensitization protocols
      developed by the pharmacy department at our institution. METHODS: A retrospective
      study was conducted at an 800-bed, urban, tertiary care, academic medical center.
      A total of 36 patients 18 years of age or older, admitted to our intensive care
      units between March 2013 and July 2017, who underwent antibiotic desensitization
      utilizing our pharmacy developed protocols were included. RESULTS: In 36
      patients, 61 desensitization cases were identified and included; 17 (47%) were
      male, 27 (75%) were Caucasian, and the median age was 55 years (range 19-94). In
      all, 15 different antibiotics were administered for desensitization, with
      meropenem (n = 12, 20%), ampicillin (n = 7, 11%), piperacillin/tazobactam (n = 7,
      11%), and penicillin (n = 7, 11%) being the most common; 59 (97%) of 61
      desensitizations were completed successfully with or without experiencing
      reactions, and 53 (89%) of the successful desensitization cases were completed
      without reactions. Two cases were categorized as anaphylaxis, which was severe
      enough to terminate the desensitization process. Of the 59 cases successfully
      completed, the 6 (10%) cases that experienced reactions were managed successfully
      during desensitization with completion of the process. Conclusion and Relevance:
      The findings suggest that our pharmacy-developed antibiotic desensitization
      protocols are successful and safe and may be adapted by other institutions.

PMID- 30234370
TI  - Advancing social and emotional well-being in Aboriginal and Torres Strait
      Islander Australians: Clinicians' reflections.
AB  - OBJECTIVE: An expert reference group met on four occasions to consider ways
      forward in terms of Indigenous mental health. This paper summarises the
      discussion and recommendations. CONCLUSION: While the negative effects of
      colonisation and trans-generational trauma continue, we propose renewed emphasis
      on improving access, cultural orientation and trauma-informed care, and a focus
      on the needs of young Indigenous Australians.

PMID- 30234371
TI  - Small Nucleolar RNA Score: An Assay to Detect Formalin-Overfixed Tissue.
AB  - Although there are millions of formalin-fixed paraffin-embedded (FFPE) tissue
      blocks potentially available for scientific research, many are of questionable
      quality, partly due to unknown fixation conditions. We analyzed FFPE tissue
      biospecimens as part of the NCI Biospecimen Preanalytical Variables (BPV) program
      to identify microRNA (miRNA) markers for fixation time. miRNA was extracted from
      kidney and ovary tumor FFPE blocks (19 patients, cold ischemia <=2 hours) with 6,
      12, 24, and 72 hours fixation times, then analyzed using the WaferGen SmartChip
      platform (miRNA chip with 1036 miRNA targets). For fixation time, principal
      component analysis of miRNA chip expression data separated 72 hours fixed samples
      from 6 to 24 hours fixed samples. A set of small nuclear RNA (snRNA) targets was
      identified that best determines fixation time and was validated using a second
      independent cohort of seven different tissue types. A customized assay was then
      developed, based on a set of 24 miRNA and snRNA targets, and a simple "snoRNA
      score" defined. This score detects FFPE tissue samples with fixation for 72 hours
      or more, with 79% sensitivity and 80% specificity. It can therefore be used to
      assess the fitness-for-purpose of FFPE samples for DNA or RNA-based research or
      clinical assays, which are known to be of limited robustness to formalin
      overfixation.

PMID- 30234373
TI  - Parents' use of mobile computing devices, caregiving and the social and emotional
      development of children: a systematic review of the evidence.
AB  - OBJECTIVES: Mobile device use is a rapidly growing, socially acceptable
      interactional habit. The impact of mobile device use on social interactions,
      including between parents and young children, is uncertain. The aim was to
      describe, synthesise and evaluate the evidence about parents' mobile device use,
      caregiving and children's social and emotional development. METHODS: Seven
      medical and social sciences databases were searched using keywords and subject
      headings. Screening for eligibility used PRISMA guidelines and scientific and
      reporting quality were assessed with standardised checklists. RESULTS: Eight
      studies met the inclusion criteria (four surveys, three qualitative and one mixed
      method investigation). This small group of studies is of diverse quality, but
      there is evidence of associations between parents' mobile device use, attention
      to caregiving and changes in child behaviour. Use of mobile devices during
      parenting activities may be infrequent and brief, but it can be a potent
      distraction that reduces caregiver responsiveness to children. CONCLUSIONS: An
      emerging body of research suggests mobile devices are associated with altered
      attention and responsivity to children by their caregivers and may change
      caregiver/child interactions. The evidence precludes questions about causality or
      discussion of impacts on child development. Knowledge gaps have been identified
      and they require future targeted research.

PMID- 30234372
TI  - Molecular Mechanisms of Phosphodiesterase-5 Inhibitors on Neuronal Apoptosis.
AB  - Phosphodiesterase-5 inhibitors (PDE5Is) have been shown to modulate cell
      death/cell survival in different in vivo and in vitro models of disease by
      activating many signaling pathways. This review aimed at elucidating how PDE5Is
      can inhibit apoptosis. In this study, we describe many signaling pathways
      involved with the mechanism of action of PDE5Is that ultimately inhibit apoptosis
      and thus promote cell survival.

PMID- 30234374
TI  - Evaluation of the Use of Exenatide Once-Weekly Suspension Autoinjector Among
      Patients With Type 2 Diabetes Mellitus and Health Care Professionals.
AB  - BACKGROUND: Ease of injection is important to patients. An autoinjector was
      developed to deliver exenatide, a glucagon-like peptide-1 receptor agonist for
      type 2 diabetes mellitus. For autoinjection, 0.06-mm exenatide-containing
      microspheres are suspended in medium-chain triglycerides. Herein, we report
      design verification and usability testing of the autoinjector for exenatide once
      weekly suspension (QWS) delivery. METHODS: Exenatide QWS in a single-chamber
      cartridge is self-injected subcutaneously with three main steps: mix, unlock, and
      inject. Design verification testing used validated testing methodology. A
      summative validation study with simulated-use scenarios evaluated unassisted
      performance on critical tasks (ease of use and the injection process). RESULTS:
      The autoinjector met specified design requirements for dose accuracy and
      torque/force. Of 104 participants enrolled (73 lay users, 16 health care
      professionals, and 15 pharmacists), 90 independently referred to instructions for
      use during testing. Users successfully achieved critical tasks on first attempt
      87-100% of the time. Approximately 78% of participants successfully completed the
      full injection scenario, including 72% of lay users reporting visual or dexterity
      impairments. Initial use errors on critical tasks included not mixing well (n =
      12), not removing needle cap (n = 8), and not holding needle to the skin for
      complete injection (n = 5). Untrained injection-naive and trained injection
      experienced lay users made the fewest errors (7% and 3%, respectively). Trained
      and untrained participants took 2:33 and 5:03 minutes, respectively, to complete
      a weekly injection. CONCLUSIONS: Users with a range of injection experience can
      rapidly learn to administer exenatide QWS autoinjector correctly, thus minimizing
      patient effort to manage their diabetes with injectable therapy.

PMID- 30234375
TI  - Spontaneous pulmonary hypertension in genetic mouse models of natural killer cell
      deficiency.
AB  - Natural Killer (NK) cells are cytotoxic innate lymphoid cells with an established
      role in the regulation of vascular structure in pregnancy and cancer. Impaired NK
      cell function has been identified in patients with pulmonary arterial
      hypertension (PAH), a disease of obstructive vascular remodeling in the lungs, as
      well as in multiple rodent models of disease. However, the precise contribution
      of NK cell impairment to the initiation and progression of PAH remains unknown.
      Here we report the development of spontaneous pulmonary hypertension in two
      independent genetic models of NK cell dysfunction, including Nfil3-/- mice, which
      are deficient in NK cells due to the absence of the NFIL3 transcription factor,
      and Ncr1-Gfp mice, which lack the NK activating receptor NKp46. Mouse models of
      NK insufficiency exhibited increased right ventricular systolic pressure and
      muscularization of the pulmonary arteries in the absence of elevated left
      ventricular end diastolic pressure, indicating that the development of pulmonary
      hypertension was not secondary to left heart dysfunction. In cases of severe NK
      cell impairment or loss, a subset of mice failed to develop pulmonary
      hypertension and instead exhibited reduced systemic blood pressure, demonstrating
      an extension of vascular abnormalities beyond the pulmonary circulation into the
      systemic vasculature. In both mouse models, the development of PAH was linked to
      elevated interleukin-23 production, whereas systemic hypotension in Ncr1-Gfp mice
      was accompanied by a loss of angiopoietin-2. Together, these results support an
      important role for NK cells in the regulation of pulmonary and systemic vascular
      function and the pathogenesis of PAH.

PMID- 30234376
TI  - Hypoxia Inhibits Adenylyl Cyclase Catalytic Activity in a Porcine Model of
      Persistent Pulmonary Hypertension of the Newborn.
AB  - OBJECTIVE: Persistent pulmonary hypertension of the newborn (PPHN) features
      hypoxemia, pulmonary vasoconstriction and impaired cardiac inotropy. We reported
      low basal and stimulated cAMP in hypoxic pulmonary artery smooth muscle cells
      (PASMC). We now examine pulmonary arterial adenylyl cyclase (AC) activity and
      regulation in hypoxic PPHN. APPROACH: PPHN was induced in newborn swine by
      normobaric hypoxia (FiO2 0.10) for 72hr; age-matched normoxic controls. We
      studied relaxation of pulmonary arterial rings to AC activator forskolin and sGC
      activator sodium nitroprusside (SNP) by isometric myography; ATP content,
      phosphodiesterase activity, AC content, isoform expression and catalytic activity
      in presence or absence of Galphas-coupled receptor agonists, forskolin, or trans
      nitrosylating agents, in human and neonatal porcine PASMC, and HEK293T stably
      expressing AC isoform 6, after 72 hour hypoxia (10% O2) or normoxia (21% O2).
      RESULTS: Relaxation to forskolin and SNP were equally impaired in PPHN PA. AC
      specific activity decreased in hypoxia. PASMC from PPHN swine had reduced AC
      activity despite culture in normoxia; transient hypoxia in vitro further
      decreased AC activity. Prostacyclin receptor ligand affinity decreased, but its
      association with Galphas increased in hypoxia. Total AC content was unchanged by
      hypoxia, but AC6 increased in hypoxic cells and PPHN pulmonary arteries.
      Impairment of AC6 activity in hypoxia was associated with nitrosylation.
      CONCLUSIONS: PPHN PA relaxation is impaired due to loss of AC activity. Hypoxic
      AC is inhibited due to s-nitrosylation; inhibition persists after removal from
      hypoxia. Down-regulation of AC-mediated relaxation in hypoxic PA has implications
      for utility of Galphas-coupled receptor agonists in PPHN treatment.

PMID- 30234377
TI  - Connexin 40 regulates lung endothelial permeability in acute lung injury via the
      ROCK1-MYPT1- MLC20 pathway.
AB  - Increased pulmonary vascular permeability is a hallmark of acute lung injury
      (ALI). Connexin 40 (Cx40) is a gap junctional protein abundantly present in the
      lung microvascular endothelium. Yet, the role of Cx40 in the regulation of lung
      vascular permeability and its underlying mechanisms are unclear. Here, we tested
      the hypothesis that Cx40 participates in regulation of lung endothelial
      permeability via a mechanism involving a Rho-associated protein kinase (ROCK)
      dependent regulation of myosin light chain (MLC). In murine models of
      intratracheal acid- or LPS-induced lung injury, genetic deficiency of Cx40
      attenuated key features of ALI including vascular barrier failure. In human
      pulmonary microvascular endothelial cells (PMVECs), thrombin-induced loss of
      transendothelial electrical resistance was attenuated by a Cx40-inhibiting
      mimetic peptide (40GAP27), Cx40-specific shRNA, or ROCK inhibitor Y27632. In
      isolated perfused mouse lung model, PAF induced lung weight gain was abrogated by
      gap junction blocker carbenoxolone, 40GAP27, Y27632, or genetic deficiency of
      Cx40. Phosphorylation of MLC20 increased drastically in both LPS-treated
      pulmonary microvascular endothelial cells and HCl-treated mouse lungs. Expression
      of ROCK1 was increased in both LPS treated PMVECs and HCl-treated mouse lungs,
      and paralleled by phosphorylation of MLC20. Co-immunoprecipitation experiments
      revealed protein-protein interaction between ROCK1 and Cx40. LPS-induced
      upregulation of ROCK1 and phosphorylation of MLC20 were blocked by knock-down of
      Cx40. LPS caused phosphorylation of myosin phosphatase targeting subunit 1, which
      could be abrogated by Y27632 or Cx40-shRNA. Our findings reveal a role of Cx40 in
      regulation of ROCK1 and MLC20 that contributes critically to lung vascular
      barrier failure in ALI.

PMID- 30234378
TI  - Identification of Two Novel Single Nucleotide Polymorphisms in the Promoter
      Region of the Pig AMP Deaminase 1 Gene Associated with Carcass Traits.
AB  - The AMP deaminase 1 (AMPD1) gene plays an important role in purine nucleotide
      interconversion and energy metabolism. In this study, two novel single nucleotide
      polymorphisms (SNPs) (g.-626 G > A and g.-566 A>G) were detected in the proximal
      promoter region of the AMPD1 gene. The Chinese indigenous pig breeds (Meishan and
      Tongcheng) had higher frequencies of the G and A alleles than Western meat-type
      breeds (Landrace and Large White) at the g.-626 G > A and g.-566 A>G loci. The
      transcriptional activity of the AMPD1 promoter carrying the haplotype H1 (A-626G
      566) was significantly (p < 0.05) higher than that of the haplotype H2 (G-626A
      566). In addition, pigs with the haplotype combination H1H1 had significantly (p
      < 0.05) higher mRNA expression levels of the AMPD1 gene than those with haplotype
      combinations H1H2 and H2H2 in two different skeletal muscles. Association
      analyses revealed that the pigs with the haplotype combination H1H1 had
      significantly higher lean meat percentage values but lower average backfat
      thickness (ABT, cm), buttock fat thickness (cm), and thorax-waist fat thickness
      (cm) values than the pigs with the haplotype combinations H1H2 and H2H2. These
      findings demonstrate that the two novel SNPs in the promoter region of the AMPD1
      gene have significant associations with pig fat deposition traits.

PMID- 30234379
TI  - Identify Cross Talk Between Circadian Rhythm and Coronary Heart Disease by
      Multiple Correlation Analysis.
AB  - Disorder in circadian rhythm has been revealed as a risk factor for coronary
      heart disease. Several studies in molecular biology established a gene
      interaction network using coronary heart susceptibility genes and the circadian
      rhythm pathway. However, cross talk between genes was mostly discovered in single
      gene pairs. There might be combination sets of genes intergraded as a unit to
      regulate the network. To resolve multiple variables in coronary heart
      susceptibility genes controlling circadian rhythm pathways, a multiple
      correlation analysis was applied to the transcriptome. Nine genes, including
      CUGBP, Elav-like family member (CELF); sodium leak channel, nonselective (NALCN);
      protein phosphatase 2 regulatory subunit B gamma (PPP2R2C); tubulin alpha 1c
      (TUBA1C); microtubule-associated protein 4 (MAP4); cofilin 1 (CFL1); myosin heavy
      chain 7 (MYH7); QKI, KH domain containing RNA binding (QKI); and maternal
      embryonic leucine zipper kinase (MELK), from coronary heart susceptibility were
      identified to predict the outcome of a linear combination of circadian rhythm
      pathway genes with R factor more than 0.7. G protein subunit alpha o1 (GNAO1),
      protein kinase C gamma (PRKCG), RBX, and G protein subunit beta 1 (GNB1) in the
      circadian rhythm pathway are characterized as combination variables to coexpress
      with coronary heart susceptibility genes.

PMID- 30234381
TI  - A Three Long Noncoding RNA-Based Signature for Oral Squamous Cell Carcinoma
      Prognosis Prediction.
AB  - Oral squamous cell carcinoma (OSCC) is one of the most common malignancies
      worldwide. Despite relative high 5-year survival rate, delayed diagnosis still
      hampers its prognosis improvement. Long noncoding RNA (lncRNA) has recently been
      demonstrated to involve in development of various cancers. This study aimed to
      identify a lncRNA-based signature by which we could accurately predict OSCC
      prognosis. We first downloaded the RNA sequencing datasets for OSCC from The
      Cancer Genome Atlas (TCGA) and divided samples into training set and validation
      set. Associations between lncRNAs' expression and OSCC overall survival (OS) were
      evaluated in training set. Further screening through Random Survival Forest (RSF)
      method identified a prognostic signature composed of three lncRNAs, including
      AC013268.5, RP11.65 L3.4, and RP11.15A1.7, and by which OSCC samples in training
      set could be divided into high-risk and low-risk group with significantly
      different OS (p < 0.001, hazard ratio [HR] = 1.873). Besides, reliability of the
      prognostic signature was confirmed in the validation set (p < 0.01, HR = 2.14).
      Receiver operating characteristic curve analysis showed the superiority of the
      signature in OSCC prognosis prediction than other clinical characteristics. Gene
      set enrichment analysis indicated that high-risk score was closely associated
      with metabolism and spliceosome related pathways. Our findings suggest that
      lncRNA should be an important biomarker for prognosis of OSCC patients.

PMID- 30234382
TI  - [18F]FDG-Labeled CGPRPPC Peptide Serving as a Small Thrombotic Lesions Probe,
      Including a Comparison with [99mTc]-Labeled Form.
AB  - PURPOSE: Fibrin is a perfect target for specific imaging of all types of
      thrombotic lesions. Cyclic peptides were introduced as the best scaffolds out of
      the different types of probes for thrombi detection. This study was conducted to
      label previously synthesized peptide-targeting fibrin with [18F]FDG and its in
      vitro and in vivo assessments. MATERIALS AND METHODS: CGPRPPC peptide
      functionalized with 6-hydrazinonicotinamide and Eei-NHS was synthesized and
      cyclized using air oxidation method. The cyclic sequences were labeled with
      [18F]FDG at 85 degrees C within 30 min. The stability studies were performed in
      human plasma. Fibrin-binding and platelet aggregation tests were performed in
      vitro. Biodistribution and scintigraphy imaging in normal mice and carotid
      thrombotic rat model were considered as in vivo studies. RESULTS: Radiolabeled
      peptides show a good stability in human plasma and also high-affinity binding for
      human fibrin. Platelet aggregation test confirmed specific binding of
      radiopeptides to fibrin. A key problem with the authors' previous research was
      inability to detect small-vessel thrombi. The results of positron emission
      tomography/computed tomography scanning show high specific uptake of [18F]FDG
      labeled CGPRPPC in small-sized thrombosis. CONCLUSION: The experiment revealed
      that radiolabeling of cyclic peptide (CGPRPPC) with [18F]FDG enables us to detect
      small thrombotic lesions in small animal models with high resolution.

PMID- 30234383
TI  - Analytical convergence in surrogate control matrices.

PMID- 30234384
TI  - Evaluation of Association of Vitamin D Receptor Genetic Polymorphism with Severe
      Chronic Periodontitis in an Ethnic Tamilian Population.
AB  - BACKGROUND: Periodontitis is a multifactorial disease characterized by
      inflammatory responses to increased levels of subgingival pathogens, resulting in
      connective tissue destruction and alveolar bone loss. The susceptibility of an
      individual is determined by the complex interplay of the host, genetic, and
      environmental factors. Vitamin D, a secosteroid hormone, interacts with its
      nuclear receptor vitamin D receptor (VDR) to regulate crucial biological
      processes, such as bone metabolism and immune function modulation. Various
      studies have been conducted in different populations to analyze the association
      of VDR gene polymorphisms with chronic periodontitis, as these polymorphisms have
      been demonstrated to play vital roles in the pathogenesis of other diseases.
      OBJECTIVE: The aim of the present study was to determine the prevalence and
      association of the VDR TaqI gene polymorphism with severe chronic periodontitis
      in an Ethnic Tamilian population. MATERIALS AND METHODS: A total of 140 subjects
      were recruited for the study, of which 70 were diagnosed with severe chronic
      periodontitis and 70 had healthy gums. Each subject's medical and dental
      histories were taken, and periodontal examinations were performed. Genomic DNA
      was extracted and genotyping of the VDR gene at the TaqI site was carried out
      using polymerase chain reaction/restriction fragment length polymorphism. The
      frequencies of genotypes and alleles were analyzed between the study groups.
      RESULTS: The frequency of homozygous TT genotype was 40%, for both the severe
      chronic periodontitis and the healthy control groups. The distribution of
      heterozygous Tt genotype was 42.9% in the severe chronic periodontitis group and
      47.1% in the healthy control group. The frequency of homozygous tt genotype was
      17.1% in the severe chronic periodontitis group and 12.7% in the healthy control
      group. Although the prevalence of genotype tt and t allele was slightly increased
      in severe chronic periodontitis patients compared with healthy controls, the
      frequency of VDR genotype between the study groups was not statistically
      significant (p-value = 0.751). CONCLUSION: This present study performed in an
      Ethnic Tamilian population does not support an association between either of the
      TaqI alleles within the VDR gene and Severe Chronic Periodontitis.

PMID- 30234380
TI  - Methane on Mars and Habitability: Challenges and Responses.
AB  - Recent measurements of methane (CH4) by the Mars Science Laboratory (MSL) now
      confront us with robust data that demand interpretation. Thus far, the MSL data
      have revealed a baseline level of CH4 (~0.4 parts per billion by volume [ppbv]),
      with seasonal variations, as well as greatly enhanced spikes of CH4 with peak
      abundances of ~7 ppbv. What do these CH4 revelations with drastically different
      abundances and temporal signatures represent in terms of interior geochemical
      processes, or is martian CH4 a biosignature? Discerning how CH4 generation occurs
      on Mars may shed light on the potential habitability of Mars. There is no
      evidence of life on the surface of Mars today, but microbes might reside beneath
      the surface. In this case, the carbon flux represented by CH4 would serve as a
      link between a putative subterranean biosphere on Mars and what we can measure
      above the surface. Alternatively, CH4 records modern geochemical activity. Here
      we ask the fundamental question: how active is Mars, geochemically and/or
      biologically? In this article, we examine geological, geochemical, and
      biogeochemical processes related to our overarching question. The martian
      atmosphere and surface are an overwhelmingly oxidizing environment, and life
      requires pairing of electron donors and electron acceptors, that is, redox
      gradients, as an essential source of energy. Therefore, a fundamental and
      critical question regarding the possibility of life on Mars is, "Where can we
      find redox gradients as energy sources for life on Mars?" Hence, regardless of
      the pathway that generates CH4 on Mars, the presence of CH4, a reduced species in
      an oxidant-rich environment, suggests the possibility of redox gradients
      supporting life and habitability on Mars. Recent missions such as ExoMars Trace
      Gas Orbiter may provide mapping of the global distribution of CH4. To
      discriminate between abiotic and biotic sources of CH4 on Mars, future studies
      should use a series of diagnostic geochemical analyses, preferably performed
      below the ground or at the ground/atmosphere interface, including measurements of
      CH4 isotopes, methane/ethane ratios, H2 gas concentration, and species such as
      acetic acid. Advances in the fields of Mars exploration and instrumentation will
      be driven, augmented, and supported by an improved understanding of atmospheric
      chemistry and dynamics, deep subsurface biogeochemistry, astrobiology, planetary
      geology, and geophysics. Future Mars exploration programs will have to expand the
      integration of complementary areas of expertise to generate synergistic and
      innovative ideas to realize breakthroughs in advancing our understanding of the
      potential of life and habitable conditions having existed on Mars. In this
      spirit, we conducted a set of interdisciplinary workshops. From this series has
      emerged a vision of technological, theoretical, and methodological innovations to
      explore the martian subsurface and to enhance spatial tracking of key volatiles,
      such as CH4.

PMID- 30234385
TI  - A Brief History of Milk Hygiene and Its Impact on Infant Mortality from 1875 to
      1925 and Implications for Today: A Review.
AB  - The objective of this review is to provide an integrated historical account of
      the complex, often convoluted events impacting milk hygiene and its resultant
      effect on infant mortality from 1875 to 1925. Heat pasteurization of cow's milk
      is necessary for rendering this important nutrient source safe for humans
      particularly infants. Developed by Louis Pasteur in 1864, pasteurization evolved
      from the commercially important parboiling of wine and beer when the Industrial
      Revolution was effecting rapid societal change in Western societies. In European
      and American societies of the early and mid-19th century, infant mortality rates
      were 30- to 60-fold higher than the current rates of five or six deaths per 1,000
      live births per year. With proof of the germ theory of disease came convincing
      evidence of the role of microbes in the transmission of infections, which led to
      the discovery that microbial pathogens were transmissible via milk. Diseases
      caused by milkborne pathogens include human and bovine tuberculosis, brucellosis,
      salmonellosis, streptococcal infections, diphtheria, and "summer diarrhea." With
      pasteurization of milk, infectious diseases with their high infant mortality
      rates decreased by only half by the early 20th century, despite concurrent
      medical and dairy hygiene advances. To further mitigate unacceptably high infant
      mortality rates, social support providers-including public health nurses and
      midwives-encouraged breastfeeding, especially among socioeconomically
      disadvantaged mothers. Improvements in pulsating vacuum milking machines also
      favorably impacted food safety by providing a clean, enclosed environment.
      Currently, bottle feeding still competes with breastfeeding as the preferred
      method, and the sale of raw, unpasteurized milk remains a contentious issue.
      Informed and responsible food safety professionals, physicians, and public health
      officials currently view breastfeeding as the preferred feeding method and milk
      pasteurization as the safer and more prudent alternative.

PMID- 30234386
TI  - Prevalence of Salmonella, Campylobacter, and Shiga Toxin-Producing Escherichia
      coli on the Surfaces of Raw Poultry Packages.
AB  - Contamination on the exterior surfaces of raw poultry packages can be transmitted
      to hands and food contact surfaces during shopping and handling. This study
      compared the level of microbial contamination and prevalence of foodborne
      pathogens on the surfaces of raw poultry packages as related to the types of
      products, types of packaging, and packaging conditions. Packages of whole
      chicken, cut-up chicken (breast and leg quarter), and ground turkey were
      purchased from retail stores. Aerobic plate counts (APCs) were significantly
      different ( P < 0.05) among types of products and packaging materials, with
      ground turkey packages and the heat-sealed, high-walled containers being the
      lowest. APCs were significantly lower ( P < 0.05) when the packages were intact
      and tight compared with intact and loose. Of the 105 packages, there were 10
      (9.5%) with the presence of either Shiga toxin-producing Escherichia coli (STEC)
      or Campylobacter; of those packages, 6 (5.7%) were positive for STEC, 7 (6.7%)
      were positive for Campylobacter, and 3 (2.9%) were positive for both pathogens on
      the surfaces. Salmonella was not detected on the surfaces of all tested packages.
      Surfaces of whole chicken packages were significantly ( P < 0.001) more likely to
      have detectable levels of Campylobacter and STEC than those of cut-up chicken
      packages. Packages that were positive for Campylobacter and/or STEC had
      significantly ( P < 0.005) higher APCs than negative packages. The results
      suggested that STEC is another significant pathogen present on the surfaces of
      poultry packages in addition to Campylobacter. The presence of STEC on the
      external packaging of raw poultry raises a concern because consumers may not
      expect such pathogens on the surfaces of poultry packages.

PMID- 30234388
TI  - Corrigendum.

PMID- 30234387
TI  - Efficacy and safety of rituximab plus bendamustine for gastric marginal zone
      lymphoma.

PMID- 30234389
TI  - Do glucagon-like peptide-1 receptor (GLP-1R) agonists have potential as adjuncts
      in the treatment of type 1 diabetes?
AB  - INTRODUCTION: Glucagon-like peptide-1 (GLP-1) is produced by the gut, stimulates
      insulin secretion from the pancreatic beta-cells, and inhibits glucagon secretion
      from the alpha-cells. The GLP-1 receptor (GLP-1R) agonists are used in the
      treatment of type 2 diabetes (T2DM). Area covered: This review covers the
      clinical trials of the GLP-1R agonists (exenatide and liraglutide) and their
      potential as adjunct treatment in type 1 diabetes mellitus (T1DM). Expert
      opinion: GLP-1R agonists are unable to increase insulin secretion, in subjects
      with T1DM, who are C-peptide negative. Also, the GLP-1R agonists either have no
      effect or cause a small inhibition of glucagon secretion in subjects with T1DM.
      There is no evidence that the GLP-1R agonists cause a major reduction in HbA1c,
      or have a major effect on hypo- or hyperglycemia in subjects with TD1M. The main
      beneficial effect of the GLP-1R agonists is probably the modest weight loss,
      which may underlie the reduction in dose of insulin used. Given that the GLP-1R
      agonists cause gastrointestinal adverse effects, and with reduced insulin doses,
      increase the risk of ketosis, it seems to me that the risk with these agents may
      outweigh any benefit in T1DM, and that they have little potential as adjuncts in
      the treatment of T1DM.

PMID- 30234390
TI  - Genetic and Functional Analyses of Two Missense Mutations in the Transcription
      Factor FOXL2 in Two Chinese Families with Blepharophimosis-Ptosis-Epicanthus
      Inversus Syndrome.
AB  - BACKGROUND: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare
      autosomal-dominant inherited disease. This study was carried out to investigate
      the genetic and functional changes within the FOXL2 gene in two Chinese families
      with BPES. MATERIALS AND METHODS: DNA was extracted from the peripheral blood of
      26 persons from two different Chinese BPES families (13 of which were affected),
      as well as 200 cataract patients to act as normal controls. FOXL2 gene mutations
      were detected using polymerase chain reaction (PCR) and DNA sequencing
      techniques. Bioinformatic analyses were performed to analyze the structures and
      functions of the mutant proteins. Wild-type and mutant FOXL2 genes were subcloned
      into pEGFP-N1 and pCDB vectors and then transfected into COS7 and HEK293T cell
      lines. We observed protein subcellular localization, and used quantitative real
      time (qRT)-PCR and western blots to assess regulation of the target OSR2 gene.
      RESULTS: We detected two novel missense mutations, c.162G>T (p.Lys54Asn) and
      c.308G>A (p.Arg103His), in the FOXL2 gene; one in each of the study families.
      Bioinformatic analyses indicated no obvious differences between the wild-type and
      mutant protein structures. However, they did predict that the two mutations were
      likely damaging to protein function. We found that the two mutated proteins were
      both largely distributed within the nucleus and that there was little found in
      the cytoplasm. The OSR2 mRNA content decreased significantly when the plasmids
      carrying the c.162G>T and c.308G>A were transfected into COS7 and HEK293 cell
      lines, when compared to the empty and the wild-type FOXL2 carrier. Western blot
      analyses indicated, that after transfecting the c.162G>T mutation, the OSR2
      protein level was relatively similar to the wild-type, but that the cells
      transfected with the c.308G>A mutation showed significantly decreased levels of
      the OSR2 protein. CONCLUSIONS: Our study broadens the BPES gene mutation spectrum
      and suggests a possible mechanism of action. It also provides reference data for
      the further studies of BPES.

PMID- 30234391
TI  - Gastroprotective effect of apricot kernel oil in ethanol-induced gastric mucosal
      injury in rats.
AB  - We investigated the gastroprotective effect of apricot kernel oil on ethanol
      induced gastric ulcer in rats. Male Wistar albino rats were divided into control,
      ethanol and apricot kernel oil + ethanol groups. The fatty acid composition of
      apricot kernel oil was determined using GC-MS. A gastric ulcer index was defined
      as the area percentage of the gastric mucosa consisting of ulcerated tissue.
      Gastric tissue was investigated by TUNEL staining for apoptosis,
      immunohistochemical iNOS staining, measurement of gastric IL-10 and IL-6
      expression by ELISA and assays of catalase, malondialdehyde and superoxide
      dismutase. The ethanol group exhibited a higher gastric ulcer score, increased IL
      6 level, increased number of inducible nitric oxide synthase-positive and TUNEL
      positive cells, and a higher MDA level compared to the control group. The apricot
      kernel oil + ethanol group exhibited significantly fewer gastric lesions compared
      to the ethanol group. Apricot kernel oil protects rat gastric mucosa against
      ethanol induced injury by its anti-inflammatory, anti-oxidative and anti
      apoptotic effects, and might be useful for reducing the severity of gastric
      ulcers.

PMID- 30234392
TI  - The dawn of precision medicine in HIV: state of the art of pharmacotherapy.
AB  - INTRODUCTION: Combination antiretroviral therapy (ART) reduces viral load to
      under the limit of detection, successfully decreasing HIV-related morbidity and
      mortality. Due to viral mutations, complex drug combinations and different
      patient response, there is an increasing demand for individualized treatment
      options for patients. Areas covered: This review first summarizes the
      pharmacokinetic and pharmacodynamic profile of clinical first-line drugs, which
      serves as guidance for antiretroviral precision medicine. Factors which have
      influential effects on drug efficacy and thus precision medicine are discussed:
      patients' pharmacogenetic information, virus mutations, comorbidities, and immune
      recovery. Furthermore, strategies to improve the application of precision
      medicine are discussed. Expert opinion: Precision medicine for ART requires
      comprehensive information on the drug, virus, and clinical data from the
      patients. The clinically available genetic tests are a good starting point. To
      better apply precision medicine, deeper knowledge of drug concentrations, HIV
      reservoirs, and efficacy associated genes, such as polymorphisms of drug
      transporters and metabolizing enzymes, are required. With advanced computer-based
      prediction systems which integrate more comprehensive information on
      pharmacokinetics, pharmacodynamics, pharmacogenomics, and the clinically relevant
      information of the patients, precision medicine will lead to better treatment
      choices and improved disease outcomes.

PMID- 30234393
TI  - A Phase 1 Trial of Oncolytic Adenovirus ICOVIR-5 Administered Intravenously to
      Cutaneous and Uveal Melanoma Patients.
AB  - Oncolytic viruses represent a unique type of agents that combine self
      amplification, lytic, and immunostimulatory properties against tumors. A local
      and locoregional clinical benefit has been demonstrated upon intratumoral
      injections of an oncolytic herpes virus in melanoma patients, leading to its
      approval in the United States and Europe for patients without visceral disease
      (up to stage IVM1a). However, in order to debulk and change the local
      immunosuppressive environment of tumors that cannot be injected directly,
      oncolyitc viruses need to be administered systemically. Among different viruses,
      adenovirus has been extensively used in clinical trials but with few evidences of
      activity upon systemic administration. Preclinical efficacy of a single
      intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus
      type 5 responsive to the retinoblastoma pathway commonly deregulated in tumors,
      led us to use this virus in a dose-escalation phase 1 trial in metastatic
      melanoma patients. The results in 12 patients treated with a single infusion of a
      dose up to 1 * 1013 viral particles show that ICOVIR5 can reach melanoma
      metastases upon a single intravenous administration but fails to induce tumor
      regressions. These results support the systemic administration of armed oncolytic
      viruses to treat disseminated cancer.

PMID- 30234395
TI  - Toxicity and Efficacy of Sequential Chemotherapy in Patients with p-stage I Non
      small Cell Lung Cancer that Recurring during Postoperative Tegafur-Uracil
      Adjuvant Chemotherapy.
AB  - It is not clear whether sequential chemotherapy can be performed immediately in
      patients with p-stage I non-small cell lung cancer recurring during a 2-year
      period of daily oral administration with tegafur-uracil (UFT) as postoperative
      adjuvant chemotherapy. Patients receiving chemotherapy within 1 month after the
      discontinuation of UFT (n = 10) (five cases with aggressive recurrent tumors) had
      the increased risk of grade 4 neutropenia, but the overall survival was not
      inferior to that in patients who received chemotherapy beginning more than 1
      month (n = 11). We could perform sequential chemotherapy immediately while paying
      attention to grade 4 neutropenia.

PMID- 30234394
TI  - Interferon-alpha Combined With Herbal Compound "Songyou Yin" Effectively Inhibits
      the Increased Invasiveness and Metastasis by Insufficient Radiofrequency Ablation
      of Hepatocellular Carcinoma in an Animal Model.
AB  - OBJECTIVE: We had previously proved that insufficient radiofrequency ablation
      (RFA) could enhance invasiveness and metastasis of hepatocellular carcinoma (HCC)
      through epithelial-mesenchymal transition (EMT), which is mediated by activating
      beta-catenin signaling. Thus, the aim of the present study was to demonstrate
      whether the combined treatment of interferon-alpha (IFN-alpha) and "Songyou Yin"
      (SYY) minimizes the pro-metastatic effects of insufficient RFA, as well as to
      explore its underlying mechanism. METHODS: Insufficient RFA was performed in an
      orthotopic nude mice model of HCCLM3 with high metastatic potential. The effects
      of IFN-alpha, SYY, and combined IFN-alpha and SYY were observed in the animal
      model. Tumor sizes, lung metastasis, and survival time were assessed.
      Immunochemistry staining, real-time polymerase chain reaction, and Western blot
      were used to examine gene expression related to metastasis and angiogenesis in
      residual cancer after insufficient RFA. RESULTS: For up to 8 weeks of treatment,
      the combined therapy significantly decreased the residual cancer sizes, minimized
      the lung metastasis rate, and prolonged the survival time of nude mice, which
      might be due to suppression of the EMT via beta-catenin signal blockade, in
      addition to attenuating angiogenesis in residual cancer after insufficient RFA.
      CONCLUSION: IFN-alpha combined with SYY significantly weakened the enhanced
      metastatic potential of residual cancer after insufficient RFA by attenuating
      EMT, which is mediated through inhibiting activation of beta-catenin. In
      addition, decreasing angiogenesis of residual cancer might also play a certain
      role.

PMID- 30234396
TI  - Impact of wearing a helmet on the risk of hospitalization and intracranial
      haemorrhage after a sports injury.
AB  - BACKGROUND: Despite their reported protective effect against the occurrence of
      head injuries, helmets are still used inconsistently in sports in which they are
      optional. We aimed to assess the impact of helmet use on the risk of
      hospitalization and intracranial haemorrhage for trauma occurring during sport
      activities. METHODS: Retrospective cohort of all patients who presented
      themselves, over an 18-month period, at the emergency department of a tertiary
      trauma centre for an injury sustained in a sport or leisure activity where the
      use of a helmet is optional. Impact of helmet use was assessed using
      multivariable regression analyses (relative risks, RR). RESULTS: Among the 1,022
      patients included in the study, half were cyclists and 40% were skiers or
      snowboarders. A total of 40 % of patients wore a helmet at the time of injury,
      18% had a head injury, 16% were hospitalized and 13% of patients with a head
      injury had an intracranial haemorrhage. Among all patients, no association was
      observed between hospital admission and helmet use. However, helmet use in
      patients with a head injury was associated with significant reductions in the
      risks of hospitalization (RR 0.41 [95% CI: 0.22-0.76]) and intracranial
      haemorrhage (RR 0.28 [95% CI: 0.11-0.71]). CONCLUSIONS: Results suggest that, in
      recreational athletes who sustain a head injury, helmet use is associated with a
      reduced risk of hospitalization (all sports) and intracranial haemorrhage
      (cyclists).

PMID- 30234398
TI  - The effect of meals on bone turnover - a systematic review with focus on diabetic
      bone disease.
AB  - INTRODUCTION: Type 2 diabetes is associated with an increased risk of bone
      fractures. Bone mineral density (BMD) is increased and bone turnover is low in
      type 2 diabetes and the increased BMD does not explain the increased fracture
      risk. However, the low bone turnover may lead to insufficient bone renewal with
      unrepaired micro-cracks and thus increase fracture risk. Ingestion of food
      acutely decreases bone resorption markers and the macronutrient composition of
      meals and meal frequency may influence bone metabolism adversely in subjects with
      unhealthy eating patterns, e.g., patients with type 2 diabetes. Areas covered:
      The treatment strategy of bone disease in type 2 diabetics is covered in this
      review. The current management of diabetic bone disease consists of anti
      osteoporotic treatment. However, anti-resorptives may further reduce an already
      low bone turnover with uncertain effects. Furthermore, the acute and long-term
      effects of meal ingestion, weight loss alone and in combination with exercise as
      well as the possible underlying mechanisms are covered in this systematic review.
      Expert Commentary: Current management of diabetic bone disease is based on
      principles of anti-osteoporotic treatment in non-diabetic subjects. However,
      studies are urged to investigate whether anti-resorptives are equally beneficial
      in type 2 diabetes as in non-diabetic individuals.

PMID- 30234397
TI  - Efficacy and Usability of a Virtual Simulation Training System for Health and
      Safety Hazards Encountered by Healthcare Workers.
AB  - OBJECTIVE: This study evaluated the efficacy, usability, usefulness, and
      desirability (UUD) of a Home Healthcare Interactive Virtual Simulation Training
      System (HH-VSTS) designed to train home healthcare workers (HHWs) and healthcare
      students to identify and respond to health and safety hazards in client homes.
      MATERIALS AND METHODS: Participants were randomly assigned to either the HH-VSTS
      training group or to the paper-based training group. The HH-VSTS group completed
      three HH-VSTS Training Modules on a laptop/desktop computer. The training modules
      addressed hazard identification, hazard rationale, and hazard response to
      electric/fire/burn, slip/trip/lift, and environmental hazards. The paper-based
      training group reviewed identical information in a written hard-copy format. Both
      groups completed an HH-VSTS Assessment module. Participants completed
      demographic/background and UUD questionnaires, and in-system metrics measured
      their performance on hazard identification, rationale, and response. RESULTS:
      Participants (n = 74) were HHWs and students in health profession programs. There
      were no significant differences in participants' ability to correctly identify
      hazards, rationale, or how to address them. Participants identified over 90% of
      hazards, although fewer participants were able to correctly identify what makes
      an item a hazard or how to manage it. For those in the HH-VSTS group, over 83%
      found the HH-VSTS easy to use, over 94% agreed the HH-VSTS was useful, and over
      80% liked it. CONCLUSION: The HH-VSTS provided and engaging, efficacious training
      that was as effective as a typical paper-based training. In addition, the HH-VSTS
      is usable by a variety of end users, regardless of computer or gaming experience.

PMID- 30234399
TI  - Management of primary refractory acute myeloid leukemia in the era of targeted
      therapies.
AB  - Primary refractory acute myeloid leukemia (AML), or primary induction failure,
      represents a continued challenge in clinical management. This review presents an
      overview of primary refractory disease and a discussion of risk factors for
      induction failure, including current evidence regarding the impact of karyotype
      and molecular mutation status on responsiveness to chemotherapy. We review the
      evidence for various treatment options for refractory AML including salvage
      chemotherapy regimens, allogeneic hematopoietic stem cell transplantation,
      targeted agents, and non-intensive therapies such as hypomethylating agents. A
      therapeutic approach to this patient population is presented, and several new and
      emerging therapies are reviewed.

PMID- 30234400
TI  - Predictive models for splenic response to JAK-inhibitor therapy in patients with
      myelofibrosis.
AB  - JAK inhibitors for myelofibrosis (MF) reduce spleen size, control constitutional
      symptoms, and may improve survival. We studied the clinical characteristics of
      548 MF patients treated with JAK inhibitors from 2008 to 2016 to better
      understand predictors of splenic response. Response was defined as a 50% decrease
      in spleen size at early (3-4 months on therapy) and late (5-12 months) timepoints
      after therapy initiation. Early response positively correlated with higher doses
      of JAK inhibitor, baseline spleen size 5-10 cm, and hemoglobin. Early response
      negatively correlated with baseline spleen size >20 cm and high WBC. The
      strongest predictor of late response was whether a patient had a response at the
      earlier timepoint (OR 8.88). Our response models suggest that clinical factors
      can be used to predict which patients are more likely to respond to JAK
      inhibitors, and those who do not achieve an early response, i.e. within 3-4
      months, should consider alternative treatments.

PMID- 30234402
TI  - Differentiating poor validity from probable impairment on the medical symptom
      validity test: a cross-validation study.
AB  - AIMS: In neuropsychological evaluations, it is often difficult to ascertain
      whether poor performance on measures of validity is due to poor effort or
      malingering, or whether there is genuine cognitive impairment. Dunham and Denney
      created an algorithm to assess this question using the Medical Symptom Validity
      Test (MSVT). We assessed the ability of their algorithm to detect poor validity
      versus probable impairment, and concordance of failure on the MSVT with other
      freestanding tests of performance validity. METHODS: Two previously published
      datasets (n = 153 and n = 641, respectively) from outpatient neuropsychological
      evaluations were used to test Dunham and Denney's algorithm, and to assess
      concordance of failure rates with the Test of Memory Malingering and the forced
      choice measure of the California Verbal Learning Test, two commonly used
      performance validity tests. RESULTS: In both datasets, none of the four cutoff
      scores for failure on the MSVT (70%, 75%, 80%, or 85%) identified a poor validity
      group with proportionally aligned failure rates on other freestanding measures of
      performance validity. Additionally, the protocols with probable impairment did
      not differ from those with poor validity on cognitive measures. CONCLUSIONS:
      Despite what appeared to be a promising approach to evaluating failure on the
      easy MSVT subtests when clinical data are unavailable (as recommended in the
      advanced interpretation program, or advanced interpretation [AI], of the MSVT),
      the current findings indicate the AI remains the gold standard for doing so.
      Future research should build on this effort to address shortcomings in measures
      of effort in neuropsychological evaluations.

PMID- 30234401
TI  - Naturally Occurring Canine Glioma as a Model for Novel Therapeutics.
AB  - BACKGROUND: Current animal models of glioma are limited to small animal models,
      which are less predictive of treatment of human disease. Canines often develop
      gliomas de novo, but the natural history of the disease is not well described.
      OBJECTIVE: We provide data for naturally occurring canine gliomas; evaluating
      medical and surgical therapies. METHODS: We reviewed medical records of pet dogs
      with a presumptive diagnosis of glioma from MRI imaging that underwent surgery as
      part of the Canine Brain Tumor Clinical Trials Program. Breed, age, sex, median
      progression-free, and overall survival times and cause of death were recorded for
      multivariate analysis. RESULTS: Ninety five dogs (56 male; mean age = 8.3 years)
      were included, but nine were excluded as final pathology was non-neoplastic.
      Gross total resection was reported in 81 cases based on postoperative MRI.
      Seventy had high-grade tumors (grade III or IV). Eighty three dogs presented with
      seizures, being the most common presenting clinical sign. Median survival after
      surgery was 723 days (95% CI 343-1103) for grade II tumors, 301 days (197-404)
      for grade III and 200 days (126-274) for grade IV (p = .009 Kaplan-Meier survival
      analysis; Log Rank test). Age (cox regression, p = .14) or sex (Kaplan-Meier
      test, p = .22) did not predict survival. CONCLUSIONS: This study establishes
      normative data for a model exploiting dogs with naturally occurring glioma, which
      can be used to test novel therapies prior to translation to human trials. Further
      work will focus on the effects of different therapies, including chemotherapy,
      radiation therapy, and immunotherapy.

PMID- 30234403
TI  - Consolidation treatment with yttrium-90 ibritumomab tiuxetan after new induction
      regimen in advanced stage follicular lymphoma: update results from the Spanish
      Lymphoma Oncology Group trial after a median follow-up of 8.5-years.

PMID- 30234404
TI  - New lessons learned in T-PLL: results from a prospective phase-II trial with
      fludarabine-mitoxantrone-cyclophosphamide-alemtuzumab induction followed by
      alemtuzumab maintenance.
AB  - Clinical trials in T-cell prolymphocytic leukemia (T-PLL) are scarce. Based on a
      precursor study testing fludarabine, mitoxantrone, and cyclophosphamide followed
      by alemtuzumab (FMC-A), we aimed to improve this regimen by upfront combining
      subcutaneous (s.c.) alemtuzumab with FMC for four cycles followed by an
      alemtuzumab-maintenance (FMCA + A). This prospective multicenter phase-II trial
      assessed response, survival, and toxicity of that regimen administered to
      pretreated (n = 4) and treatment-naive (n = 12) T-PLL patients. The best overall
      response rate after FMCA was 68.8% (n = 11) including five CRs (31.3%) and six
      PRs (37.5%). Six patients entered the alemtuzumab-maintenance. Median overall and
      progression-free survival was 16.7 and 11.2 months, respectively. Hematologic
      toxicities were the most frequent grade 3/4 side effects. A reduced incidence of
      CMV-reactivations was attributed to the prophylactic administration of
      valganciclovir. Overall, FMCA + A did not improve the efficacy of the FMC-A
      regimen or of single i.v. alemtuzumab. It suggests that a chemotherapy backbone
      prevents efficient alemtuzumab dosing and confirms that intravenous alemtuzumab
      is to be preferred over its s.c. route in T-PLL. ClinicalTrials.gov identifier:
      NCT01186640.

PMID- 30234405
TI  - Prognostic impact of diagnosis to treatment interval (DTI) in diffuse large B
      cell lymphoma patients: a real-life monocentric study.

PMID- 30234406
TI  - Frequent and reliable engraftment of certain adult primary acute lymphoblastic
      leukemias in mice.

PMID- 30234407
TI  - Treatment patterns, health care resource utilization, and costs in patients with
      relapsed/refractory Hodgkin lymphoma treated with brentuximab vedotin.
AB  - Data are limited on the real-world utilization and costs of brentuximab vedotin
      (BV) among patients with relapsed/refractory Hodgkin lymphoma (rrHL) in the
      United States. A total of 219 BV patients identified from the Truven
      MarketScan(r) databases were followed up for a median of 2.9 years before and 1.0
      year after initiation of BV. Of these patients, 109 (50.6%) received systemic
      therapy after BV (post-BV ST). Median duration of treatment was short for BV (2.1
      months) and post-BV ST treatment (1.3 months); time to next treatment was 6.2 and
      9.1 months, respectively. Average total US dollar 2014 costs/person for BV and
      post-BV ST line of therapy were $167,152 and $132,115, respectively; mean per
      patient-per-month costs for BV and post-BV ST were $30,434 and $29,138,
      respectively. Findings underscore the unmet medical need and substantial economic
      burden in BV-treated patients with rrHL.

PMID- 30234408
TI  - A Qualitative Study of Psychological Outcomes in Avalanche First Responders.
AB  - : Dolan, Nathalia, and Christopher Tedeschi. A qualitative study of psychological
      outcomes in avalanche first responders. High Alt Med Biol 00:000-000, 2018.
      OBJECTIVES: We sought to characterize the mental health morbidity associated with
      avalanche rescue, and to generate hypotheses as to how such morbidity may be
      mitigated. MATERIALS AND METHODS: Avalanche first responders were recruited
      through online advertisements, social media, direct outreach, and e-mail
      solicitation. Thirteen subjects were selected for inclusion. Each subject
      participated in a semistructured interview. Transcripts were coded and
      thematically analyzed. RESULTS: Themes identified from interviews fell into three
      broad categories: long-term effects of rescue participation, assessments of
      psychological support, and recommendations for change. Symptoms of substance use
      disorder, depression, anxiety, panic, acute stress disorder, and posttraumatic
      stress disorder were evident in the interviews, as was evidence of adverse
      effects on subjects' personal relationships. Many respondents described a
      deficiency of formal psychological support for avalanche first responders, often
      limited to after-action debriefs of varying effectiveness. Nevertheless, subjects
      who received high-quality professional psychological support considered it
      helpful. Participants' suggestions for improvement focused on formalizing
      preincident psychological preparation and postincident support. CONCLUSIONS:
      Avalanche responders may experience long-lasting, work-related psychological
      effects. There is a paucity of effective psychological preparation and support
      for this population of first responders. Formal psychological support is
      positively received when available. Further study is required to evaluate
      particular interventions in this specific population.

PMID- 30234409
TI  - Oxidative stress in chronic lymphocytic leukemia: still a matter of debate.
AB  - There is a large body of evidence showing a strong correlation between
      carcinogenesis of several types of human tumors, including chronic lymphocytic
      leukemia (CLL), and oxidative stress (OS). The mechanisms by which OS may promote
      cancer pathogenesis have not been completely deciphered yet and, in CLL, as in
      other neoplasms, whether OS is a primary cause or simply a downstream effect of
      the disease is still an open question. It has been demonstrated that, in CLL, OS
      concomitantly results from increased reactive oxygen species (ROS) production,
      mainly ascribable to CLL cells mitochondrial activity, and impaired antioxidant
      defenses. Interestingly, OS evaluation in CLL patients, at diagnosis, seems to
      have a prognostic significance, thus getting new insights in the biological
      comprehension of the disease with potential therapeutic implications.

PMID- 30234410
TI  - Mini-review of hair cortisol concentration for evaluation of Cushing syndrome.
AB  - INTRODUCTION: The diagnosis of endogenous Cushing syndrome is often challenging
      and requires multiple repeated blood, urine, and saliva tests to detect elevated
      cortisol levels. Hair cortisol concentration has been described as a marker of
      long-term exposure to systemic cortisol in patients with Cushing syndrome. Like
      hemoglobin A1c is used to detect serum glucose exposure over months, segmental
      hair cortisol can help identify patients with milder forms of and/or periodic or
      cyclical Cushing syndrome, which may reduce time and costs associated with
      collection of urine, salivary, and serum cortisol. Areas covered: Success of hair
      cortisol in detection of Cushing syndrome will be discussed in context of current
      literature, including differences between total or segmental hair cortisol in
      accurately determining timeline of cortisol exposure. Optimal methods of hair
      collection, storage, processing, and analysis and efforts toward standardization
      will be a major focus. Expert commentary: Recent evidence suggests increased
      sensitivity and specificity of hair cortisol in detecting Cushing syndrome.
      Future guidelines should consider this test as a routine part of the repertoire
      of screening tests for Cushing syndrome. Possible confounders to explain
      discrepant results in the literature will be discussed.

PMID- 30234411
TI  - Bioactivity and cell metabolism of in vitro digested sweet cherry (Prunus avium)
      phenolic compounds.
AB  - In this study, the bioaccessibility of phenolic compounds after in vitro
      gastrointestinal digestion of two cherry cultivars was assessed. The phenolic
      profile was modified during in vitro digestion, with a considerable decrease of
      total and individual phenolic compounds. Hydroxycinnamic acids and especially
      coumaroylquinic acids showed the highest bioaccessibility. Isomerisation of
      caffeoylquinic and coumaroylquinic acids was observed after in vitro digestion.
      Modification of the phenolic profile after digestion resulted in an increased or
      decreased scavenging activity depending on the assay. In vitro digested phenolic
      rich fractions also showed antiproliferative activity against SW480 but no effect
      against Caco-2 cell lines. Both Caco-2 and SW480 cell lines were able to
      metabolise cherry phenolic compounds with remarkable differences. An accumulation
      of glycosylated flavonols was observed in SW480 medium. In conclusion, phenolic
      compounds from cherries and especially hydroxycinnamic acids were efficiently
      released and remained bioaccessible after in vitro digestion, resulting in
      antioxidant and antiproliferative activities.

PMID- 30234412
TI  - Uveitis of Unknown Etiology: Clinical and Outcome features. A Retrospective
      Analysis of 355 Patients.
AB  - PURPOSE: Despite the huge advance in diagnostic technics, about one-third of
      uveitis is still considered of unknown etiology. In this study, we aimed to
      report their clinical features and to describe how a diagnosis has been finally
      reached for some patients. METHODS: We retrospectively reviewed all patients with
      uveitis referred to our tertiary center between 2002 and 2016. The unknown
      etiology was admitted after a new ophthalmologic examination and a full work-up
      in internal medicine in our tertiary center. RESULTS: Among 957 patients with
      uveitis, 355 had uveitis of unknown etiology. The clinical and epidemiological
      characteristics of this subgroup were no different from those with a known
      etiology. Out of 104 patients who were followed-up for more than 1 year, a
      diagnosis was finally achieved in 20 patients. The diagnosis was determined
      either because of the occurrence of a new clinical symptom (n = 10), a
      new/repeated non-ophthalmologic investigation (n = 7), or a new/repeated
      ophthalmic exam (n = 3). CONCLUSION: A prolonged follow-up, with repeated exams,
      may allow the determination of an etiology in about one-fifth of uveitis
      initially considered as idiopathic.

PMID- 30234413
TI  - Imaging appearance of myelopathy secondary to nitrous oxide abuse: a case report
      and review of the literature.
AB  - BACKGROUND: The abuse of nitrous oxide (N2O) can induce Vitamin B12 deficiency
      that subsequently leads to central nervous demyelination, myelopathy and
      peripheral neuropathy. Although myelopathy has been reported in the past, the
      specific locations and prognosis of the disease are still unclear. METHODS: We
      report the case of a 22-year-old male who presented with quadriplegia that began
      after a 3-month history of inhalation of N2O. We summarized the clinical data of
      this entity and performed a comprehensive literature review of various
      presentations and MRI features of myelopathy secondary to N2O abuse. RESULTS: In
      combination with previous reports of 14 cases, we found that the onset of the
      disease was usually subacute, and the majority of patients (92.85%) were young
      men. There was no definite relationship between myelopathy and the amount or
      duration of N2O inhalation. The most common clinical manifestation was sensory
      ataxia, and the cervical spinal cord was the most frequently impaired area of the
      whole spinal cord. The spinal cord lesions had a high signal intensity on T2
      weighted MRI and usually involved more than three spinal segments and impaired
      the posterior column more significantly. Most patients recovered well after
      vitamin B12 supplementation. CONCLUSIONS: Myelopathy secondary to N2O abuse is
      generally seen in young men. The clinical diagnosis mainly depends on a history
      of N2O inhalation and the characteristic imaging changes in the posterior
      cervical spinal cord. Early diagnosis and intervention are important for a
      satisfactory prognosis.

PMID- 30234415
TI  - Clove Bud Polyphenols Alleviate Alterations in Inflammation and Oxidative Stress
      Markers Associated with Binge Drinking: A Randomized Double-Blinded Placebo
      Controlled Crossover Study.
AB  - Acetaldehyde, the major cytotoxin formed by the metabolism of alcohol, is
      responsible for liver injury, extracellular matrix alterations, inflammation, and
      hangover in heavy drinkers. This study aimed to demonstrate the efficacy of a
      standardized polyphenolic extract of clove buds (Clovinol) in ameliorating the
      oxidative stress and inflammation caused by the accumulation of acetaldehyde
      after binge drinking. We used a randomized, double-blinded crossover study with
      16 male social drinkers. The subjects were randomized into two groups of eight
      subjects and received either placebo or Clovinol in a single hard shell gelatin
      capsule (250 mg * 1) per day. The dosage of alcohol was 1 g/kg body weight/day.
      After 2 weeks of washout period, the treatment regime was reversed. Blood samples
      were drawn at 0, 0.5, 2, 4, and 12 h after treatment with either placebo or
      Clovinol, and biochemical parameters were analyzed. Hangover severity score was
      determined by using a validated questionnaire as reported earlier. Results showed
      faster elimination of blood acetaldehyde with significant decreases in oxidative
      stress, lipid peroxidation, C-reactive protein, interleukin-6, and significant
      enhancement in glutathione and superoxide dismutase as compared with placebo
      along with an overall reduction of 55.34% in hangover severity in Clovinol
      treated subjects. This study demonstrated the efficacy of clove bud polyphenols
      for alleviating alcohol-related side effects among social drinkers at the studied
      dose.

PMID- 30234414
TI  - Resurfacing with Ablation of Periorbital Skin Technique: Indications, Efficacy,
      Safety, and 3D Assessment from a Pilot Study.
AB  - OBJECTIVES AND BACKGROUND: Nowadays, several approaches for skin rejuvenation of
      the lower eyelid are available. We present a new technique of resurfacing with
      ablation of periorbital skin (RAP) performed in a single session. METHODS: This
      is a retrospective study involving 20 patients showing skin elastosis with or
      without evidence of the nasojugal fold and atrophic and dyschromic skin or
      needing a combined approach of transconjuntival lower blepharoplasty for fat bag
      removal. RAP technique is assessed in terms of efficacy, safety, and 3D
      evaluation of results at 6 months' follow-up. RESULTS: Global Assessment
      Improvement Scale results highlighted an improvement in all cases, for both
      physicians (blinded to treatment) and individual subjects. Only minor adverse
      events (edema, erythema, and discoloration) were reported in almost all patients,
      lasting 2-3 weeks after treatment, and were resolved without intervention. A 3D
      imaging tool revealed the reduction of medium protrusions and depressions and an
      improved texture at 2 months. Skin recovery was inversely correlated with
      hemoglobin reduction. CONCLUSIONS: RAP seems to offer expert dermatologists a
      safe and clinically effective technique for skin rejuvenation of lower eyelids,
      without significant adverse events. Further studies will be performed to confirm
      our results.

PMID- 30234416
TI  - Prelacrimal approach for nasolacrimal duct excision in the management of lacrimal
      system tumours.
AB  - PURPOSE: To report a case of a lacrimal sac tumour and describe a prelacrimal
      approach to the maxillary sinus to excise the nasolacrimal duct in its
      management. To our knowledge, this approach has not been adapted to remove the
      nasolacrimal duct for the management of pathological processes involving the
      nasolacrimal system. METHODS: A 58-year-old female patient presented with a 6
      month history of epiphora. A lacrimal sac mass was identified, and a biopsy
      revealed squamous cell carcinoma. Surgical excision was performed via a combined
      external and endoscopic prelacrimal approach. RESULTS: A prelacrimal approach to
      the maxillary sinus to excise the nasolacrimal duct in combination with an
      external approach facilitated an en-bloc excision of the nasolacrimal apparatus.
      This allowed preservation on the entire inferior turbinate following
      reconstitution of the lateral nasal wall at the completion of the procedure.
      CONCLUSION: The endoscopic endonasal prelacrimal approach to the maxillary sinus
      is a useful method to approach and excise the nasolacrimal duct in the management
      of nasolacrimal pathology.

PMID- 30234417
TI  - ADHD 24/7: Circadian clock genes, chronotherapy and sleep/wake cycle
      insufficiencies in ADHD.
AB  - OBJECTIVES: The current paper addresses the evidence for circadian clock
      characteristics associated with attention-deficit hyperactivity disorder (ADHD),
      and possible therapeutic approaches based on chronomodulation through bright
      light (BL) therapy. METHODS: We review the data reported in ADHD on genetic risk
      factors for phase-delayed circadian rhythms and on the role of photic input in
      circadian re-alignment. RESULTS: Single nucleotide polymorphisms in circadian
      genes were recently associated with core ADHD symptoms, increased evening
      orientation and frequent sleep problems. Additionally, alterations in exposure
      and response to photic input may underlie circadian problems in ADHD. BL therapy
      was shown to be effective for re-alignment of circadian physiology toward
      morningness, reducing sleep disturbances and bringing overall improvement in ADHD
      symptoms. The susceptibility of the circadian system to phase shift by timed BL
      exposure may have broad cost-effective potential implications for the treatment
      of ADHD. CONCLUSIONS: We conclude that further research of circadian function in
      ADHD should focus on detection of genetic markers (e.g., using human skin
      fibroblasts) and development of BL-based therapeutic interventions.

PMID- 30234418
TI  - Evolution and Predictors of Patient-Caregiver Concordance on States of Life
      Sustaining Treatment Preferences over Terminally Ill Cancer Patients' Last Six
      Months of Life.
AB  - BACKGROUND: Patient-caregiver concordance on end-of-life (EOL) care preferences
      is poor, but changes in this concordance have not been longitudinally explored as
      patient death approaches, potentially distorting the extent of concordance. Cross
      sectional studies cannot disentangle whether the extent of concordance is
      facilitated or hindered by dyads' specific preferences, prognostic awareness,
      physical and psychological well-being, and quality of life, or whether these
      variables were enhanced or worsened by patient-caregiver concordance on EOL care
      preferences. OBJECTIVE: To examine the evolution of and factors facilitating or
      hindering patient-caregiver concordance on life-sustaining treatment (LST)
      preferences over cancer patients' last six months. DESIGN: Longitudinal study
      design. METHODS/SUBJECTS: Patient-caregiver concordance on LST preference states
      (patterns) was examined among 215 cancer patient-caregiver dyads in patients'
      last six months by hidden Markov modeling. Concordance on LST preference states
      was determined by percent agreement and kappa coefficients. Predictors of
      concordance on LST preference states were tested by hierarchical generalized
      linear modeling with logistic regression, with concordance and time-varying,
      modifiable independent variables arranged in a distinct time sequence. RESULTS:
      Patient-caregiver concordance on LST preference states was poor and improved only
      slightly over cancer patients' last six months. Concordance on LST preference
      states was significantly more likely in patients with greater physical symptom
      distress. Caregivers were more likely to concur with their relative's LST
      preference states if caregivers uniformly rejected all LSTs or accepted
      nutritional support while rejecting other aggressive LSTs for their relative.
      DISCUSSION/CONCLUSION: Patient symptom distress and caregiver rejection of
      aggressive LSTs predicted greater patient-caregiver concordance on LST preference
      states in patients' last six months. To encourage patients and caregivers to
      discuss LST preferences, clinicians should facilitate caregivers' understanding
      of patients' LST preferences and LST efficacy at EOL and adjustment to their
      beloved's inevitable death when his/her physical symptoms still wax and wane,
      thus providing personalized and value-concordant EOL care for dying cancer
      patients.

PMID- 30234419
TI  - Men's Perspectives of a Gender-Sensitized Health Promotion Program Targeting
      Healthy Eating, Active Living, and Social Connectedness.
AB  - Men in high income countries have poorer dietary habits and higher rates of
      overweight and obesity than women. A major challenge with engaging men in health
      promotion is the perception that attention to one's health runs counter to
      masculine identities. Contemporary health promotion programs are believed to hold
      little "manly" appeal and often fail to engage and retain men. The HAT TRICK
      program was designed to engage men with their health by delivering an
      intervention in collaboration with a semi-professional ice hockey team. The
      program included 12 weekly sessions promoting healthy eating, active living, and
      social connectedness among men. Gender-sensitized elements were reflected in the
      program design, setting, content, and delivery. Semistructured telephone
      interviews were conducted with 23 men to explore perspectives of their
      participation in the gender-sensitized intervention. Participants were white
      (100%) with a mean age of 53 years ( SD +/- 9.9), Body Mass Index (BMI) of 37
      kg/m2 ( SD +/- 6.8), and waist circumference of 127 centimeters ( SD +/- 14.5).
      Inductive thematic analysis revealed three overarching themes, including: (a)
      Harnessing nostalgia for past masculinities: "Closet athletes from 30 years ago,"
      (2) Offsetting resistance to change with sensible health advice: "Don't give up
      drinking beer, just have less," and (3) Gendered social spaces for doing health:
      "A night out with the guys," The findings support the value of gender-sensitized
      approaches to men's health promotion. Further research is needed to identify
      which gender-sensitized elements are critical to engaging men in healthy
      lifestyle changes.

PMID- 30234420
TI  - Impact of Cross-Contamination Concentrations of Doxycycline Hyclate on the
      Microbial Ecosystem in an Ex Vivo Model of the Pig's Cecum.
AB  - AIMS: Cross-contamination of feed with antibiotics causes pigs to become
      unintentionally exposed to low concentrations of antibiotics. This study
      investigates the effect of residues of doxycycline hyclate (DOX) in an ex vivo
      model of the intestinal tract of pigs, focusing on the microbial community,
      microbial activity, and the enrichment of resistant bacteria and resistance
      genes. RESULTS: The effect of three concentrations DOX were tested; 1 and 4 mg/L
      correspond to the intestinal concentrations when pigs are fed a compound feed
      containing 3% of a therapeutic dose, and a reference concentration of 16 mg/L.
      These were continuously administered to a chemostat, simulating the microbial
      ecosystem of the pig cecum and inoculated with cecal content of organically grown
      pigs. The administration of even the lowest DOX concentration caused a
      significant decrease in bacterial activity, while the microbial community profile
      appeared to remain unaffected by any of the concentrations. A concentration of 1
      mg/L DOX caused minor selection pressure for tetracycline-resistant Escherichia
      coli but no other groups enumerated with plate cultivation, while 4 mg/L induced
      major enrichment of tetracycline-resistant E. coli, Enterobacteriaceae and total
      anaerobes. High abundances of tet(Q), tet(M), tet(W), tet(O), and tet(B) were
      detected in the inoculum and also before antibiotic administration in the
      chemostat and did not significantly increase during administration of 1 and 4
      mg/L DOX. Only 16 mg/L DOX caused minor enrichments. CONCLUSIONS: Cross
      contamination concentrations of doxycycline, as a result of cross-contamination,
      cause a selection pressure for resistant bacteria and negatively affect microbial
      activity.

PMID- 30234422
TI  - High-Level Multidrug-Resistant Escherichia coli Isolates from Wild Birds in a
      Large Urban Environment.
AB  - Intensive clinical use of antibiotics together with inadequate sanitation in an
      urban environment may contribute to the dissemination of multidrug-resistant
      (MDR) bacteria in the community. Wild birds living in these areas may become
      colonized with such organisms and further disseminate these resistant bacteria.
      In this study, we examined Escherichia coli isolates from the intestine of wild
      birds in Rio de Janeiro, Brazil, for those expressing extended-spectrum beta
      lactamase (ESBL), carbapenemase, and other drug resistances. We obtained 353 E.
      coli isolates from 112 birds admitted to three wildlife centers in Rio de Janeiro
      state, from July 2010 to December 2013. MDR isolates were found in 43 (38%)
      birds, including 14 carrying E. coli isolates that expressed ESBL. All ESBL
      encoding genes were blaCTX-M type, and no carbapenemase-producing isolates were
      found. MDR isolates belonged to a variety of lineages. Multilocus sequence type
      clonal complexes 648 and 155 accounted for carriage in 9 (21%) of 43 birds with
      MDR isolates. The study birds were nonmigratory, and the bacteria obtained from
      them likely mirrored urban circulating genotypes. Altogether, these findings
      indicate a high level of environmental contamination with clinically relevant
      drug resistance genes in Rio de Janeiro. A large proportion of the MDR strains
      belonged to clonal lineages.

PMID- 30234421
TI  - Does advance care planning in addition to usual care reduce hospitalisation for
      patients with advanced heart failure: A systematic review and narrative
      synthesis.
AB  - BACKGROUND:: People with advanced heart failure have repeated hospital
      admissions. Advance care planning can support patient preferences, but studies in
      people with heart failure have not been assessed. AIM:: To evaluate the
      literature regarding advance care planning in heart failure. DESIGN:: Systematic
      review and narrative analysis (PROSPERO CRD42017059190). DATA SOURCES::
      Electronic databases were searched (1990 to 23 March 2017): MEDLINE(R), Cochrane
      Library, CINAHL and Scopus. Four journals were hand searched. Two independent
      researchers screened against eligibility criteria. One reviewer extracted all
      data and a sample by a second. Quality was assessed by Cochrane Risk of Bias or
      the Critical Appraisal Skills Programme Tool for Cohort Studies. RESULTS:: Out of
      the 1713 articles, 8 were included representing 14,357 participants from
      in/outpatient settings from five countries. Two randomised controlled trials and
      one observational study assessed planning as part of a specialist palliative care
      intervention; one randomised controlled trial assessed planning in addition to
      usual cardiology care; one randomised controlled trial and one observational
      study assessed planning in an integrated cardiology-palliative care model; one
      observational study assessed evidence of planning (advance directive) as part of
      usual care and one observational study was a secondary analysis of trial
      participants coded Do Not Attempt Cardiopulmonary Resuscitation. Advance care
      planning: (1) reduced hospitalisation (5/7 studies); (2) increased referral/use
      of palliative services (4/4 studies); and (3) supported deaths in the patient
      preferred place (2/2 studies). CONCLUSION:: Advance care planning as part of
      specialist palliative care reduces hospitalisation. Preliminary studies of
      planning integrated into generic care, accessing specialist palliative care
      support if needed, are promising.

PMID- 30234423
TI  - Rethinking End-of-Life Care and Palliative Care: Learning From the Illness
      Trajectories and Lived Experiences of Terminally Ill Patients and Their Family
      Carers.
AB  - Lynn conceptualized end-of-life (EoL) care for patients with advanced chronic
      progressive illnesses as a combination of life-preserving/palliative care, the
      palliative aspect gradually becoming the main focus as death approaches. We
      checked this concept by exploring the advanced-terminal illness trajectories of
      50 patients. Strategies heralding active therapy exhaustion were the catalyst for
      a participant's awareness of terminality, but were not a decisive factor in the
      divergent EoL care pathways we detected. The terms life-preserving and palliative
      do not adequately capture EoL care pathways due to their conceptual ambiguity.
      Conversely, the concept of EoL care encompassing three palliative care modalities
      ( life-prolonging palliative therapy, restorative palliative care, and symptom
      oriented [only] palliative care), each harboring a different blend of life
      preserving and symptom-comforting aspects, proved adequate. These modalities
      could run serially, oscillatorily, or parallelly, explaining the divergent EoL
      care pathways. We suggest an adjustment of the model of Lynn and reconsider the
      traditional palliative care concept.

PMID- 30234424
TI  - Transcallosal Fiber Disruption and its Relationship with Corresponding Gray
      Matter Alteration in Patients with Diffuse Axonal Injury.
AB  - Diffuse axonal injury (DAI) is characterized by diffuse white matter (WM)
      disruption caused by shearing forces acting on the brain. Cortical atrophy can be
      accompanied by WM disruption, which is assumed to reflect the loss of neuron cell
      bodies in gray matter (GM) regions adjacent to disrupted WM. It remains unclear
      whether WM disruption leads to regional GM alteration in DAI. The aim of the
      present study was to assess WM disruption and corresponding GM alterations in
      patients with DAI using a connectome-based approach. Twenty-four patients and 24
      healthy controls underwent magnetic resonance imaging with diffusion tensor
      imaging (DTI). Deterministic fiber tracking was conducted to investigate
      structural connectivity between the corpus callosum (CC) and each pre-defined
      regional cortical area. We calculated 85 * 85 connectivity matrices for
      fractional anisotropy (FA). Group comparisons were conducted to identify abnormal
      connectivity in patients. Further, the regional cortical volume of each
      connectivity matrix was compared between patients and controls. Finally,
      correlation analyses between the matrices and regional cortical volumes were
      performed within the patient group. Connectome analyses revealed that, compared
      with controls, patients exhibited a FA reduction in connectivity via CC to 32
      cortical regions including the frontal, parietal, and occipital cortices. Among
      these regions, GM volume was reduced in 19 of 32 regions. There were no
      significant correlations between WM disruption in which abnormal connectivity was
      identified and the corresponding GM alterations. These results suggest that GM
      pathology is, at least in part, independent of the corresponding WM damage in
      DAI.

PMID- 30234425
TI  - Precision medicine in clinical practice.
AB  - In reports of clinical efficacies of new therapies in prospective randomized
      controlled trials, evidence showing proportion of respondents who meet the
      minimum clinically important difference in prespecified clinical end points are
      often not presented. Such reporting deficiency negatively impacts precision
      medicine practice in clinics. As all patient-centric decisions are binary,
      patients must be understood as individuals and not group averages. At any visit,
      a clinician must decide whether to prescribe or not to prescribe a unique therapy
      to a unique patient at that unique time. I submit my perspective here that
      reports of clinical evidence of drug efficacy must routinely include data and
      summary statistics from dichotomization of clinical end points at the
      prespecified minimum clinically important difference or higher cutoffs to inform
      personalized treatment decisions in clinics.

PMID- 30234426
TI  - Use of an Electronic Journal Club to Increase Access to and Acceptance of
      Palliative Care Literature across General Pediatricians and Pediatric
      Subspecialties.
AB  - CONTEXT: Implementation of pediatric palliative care as a primary practice
      relevant for all pediatricians and pediatric subspecialists requires a grounding,
      shared knowledge. This study reports on the innovative application of a monthly
      Palliative Care E-Journal Club (Pal Care Club) to foster shared palliative care
      knowledge hospital wide. OBJECTIVES: To explore the impact of a monthly
      electronic journal club to increase the number of palliative care-relevant
      articles read and discussed and to enhance provider comfort with the integration
      and introduction of palliative care. METHODS: A single cohort, predesign-post
      design was utilized to explore the impact of a monthly palliative care electronic
      journal club. RESULTS: Preintervention barriers to reading pediatric palliative
      care literature were primarily access and time. The mean of paired differences
      (post-pre) for the number of full-text articles read per month was 2.56 (SD =
      1.25). The journal club intervention increased participant personal comfort with
      integrating palliative care principles at the bedside (p < 0.0001) and
      introducing pediatric palliative care to patients and families (p < 0.0001).
      CONCLUSION: An electronic journal club is a feasible and acceptable means of
      increasing number of palliative care articles read and discussed across an
      institution as well as enhancing pediatric palliative care knowledge across
      subspecialist and general pediatric services.

PMID- 30234428
TI  - Emerging Applications of Photobiomodulation Therapy: The Interaction Between
      Metabolomics and the Microbiome.

PMID- 30234427
TI  - Effect of borneol as a penetration enhancer on brain targeting of nanoliposomes:
      facilitate direct delivery to neurons.
AB  - AIM: This study is aimed to evaluate borneol as a penetration enhancer to improve
      brain target of nanoliposome. MATERIALS & METHODS: Effects of borneol on
      pharmacokinetics, targeting efficiency, brain subareas distribution and neuron
      targeting level and pathway were studied by fluorescence spectrophotometry and
      immunofluorescence. RESULTS: Borneol did not influence physicochemical property
      of doxorubicin hydrochloride nanoliposome (Dox-nanoLips). Co-administration of
      Dox-nanoLips with borneol elevated brain-target efficiency due to selective
      distribution increase in the cerebral cortex and hippocampus without difference
      in contralateral hemisphere. Borneol improved neuronal-targeting level of Dox
      nanoLips in the cortex, CA3 and dentate gyrus regions via opening tight junctions
      of blood-brain barrier and then bypassing astrocyte. CONCLUSION: Borneol is
      potential to be a promising penetration enhancer for nanocarrier to target
      neurons.

PMID- 30234429
TI  - Comparative Effectiveness of Surgery for Traumatic Acute Subdural Hematoma in an
      Aging Population.
AB  - There is uncertainty as to the optimal initial management of patients with
      traumatic acute subdural hematoma, leading to regional variation in surgical
      policy. This can be exploited to compare the effect of various management
      strategies and determine best practices. This article reports such a comparative
      effectiveness analysis of a retrospective observational cohort of traumatic acute
      subdural hematoma patients in two geographically distinct neurosurgical
      departments chosen for their - a-priori defined - diverging treatment
      preferences. Region A favored a strategy focused on surgical hematoma evacuation,
      whereas region B employed a more conservative approach, performing primary
      surgery less often. Region was used as a proxy for preferred treatment strategy
      to compare outcomes between groups, adjusted for potential confounders using
      multivariable logistic regression with imputation of missing data. In total, 190
      patients were included: 108 from region A and 82 from region B. There were 104
      males (54.7%). Matching current epidemiological developments, the median age was
      relatively high at 68 years (interquartile range [IQR], 54-76). Baseline
      characteristics were comparable between regions. Primary evacuation was performed
      in 84% of patients in region A and in 65% of patients in region B (p < 0.01).
      Mortality was lower in region A (37% vs. 45%, p = 0.29), as was unfavorable
      outcome (53% vs. 62%, p = 0.23). The strategy favoring surgical evacuation was
      associated with significantly lower odds of mortality (odds ratio [OR]: 0.43; 95%
      confidence interval [CI]: 0.21-0.88) and unfavorable outcome (OR: 0.53; 95% CI:
      0.27-1.02) 3-9 months post-injury. Therefore, in the aging population of patients
      with acute subdural hematoma, a treatment strategy favoring emergency hematoma
      evacuation might be associated with lower odds of mortality and unfavorable
      outcome.

PMID- 30234430
TI  - "It Changed Our Outlook on How We Want to Live": Cancer as a Transformative
      Health Experience for Young Adult Survivors and Their Family Members.
AB  - Although young adult cancer survivors (YACSs) and their families face unique
      psychosocial and health-related challenges related to cancer, little is known
      about how the illness experience of cancer may positively transform their mental,
      physical, and social well-being following primary treatment. We conducted
      individual qualitative interviews with 30 YACSs and 21 of their family members.
      Participants described positive transformations as (a) perspective shifts on
      health and risk, (b) behavior changes toward more proactive healthy living, and
      (c) opportunities for more open communication about wellness. Few participants
      reported little to no transformation based on a fatalistic view of their
      diagnosis. Our findings illuminate important implications for health promotion
      and support in this population, including the role health care providers can play
      following primary treatment. We also discuss how YACSs can serve as important
      advocates for others and the need for more work exploring how and why positive
      illness transformations take place.

PMID- 30234433
TI  - Treatment decisions in MS: Shifting the goal posts or changing how we see them?

PMID- 30234431
TI  - Silent lesions on MRI imaging - Shifting goal posts for treatment decisions in
      multiple sclerosis.
AB  - BACKGROUND: The current best practice suggests yearly magnetic resonance imaging
      (MRI) to monitor treatment response in multiple sclerosis (MS) patients.
      OBJECTIVE: To evaluate the current practice of clinicians changing MS treatment
      based on subclinical new MRI lesions alone. METHODS: Using MSBase, an
      international MS patient registry with MRI data, we analysed the probability of
      treatment change among patients with clinically silent new MRI lesions. RESULTS:
      A total of 8311 MRI brain scans of 4232 patients were identified. Around 26.9%
      (336/1247) MRIs with one new T2 lesion were followed by disease-modifying therapy
      (DMT) change, increasing to 50.2% (129/257) with six new T2 lesions. DMT change
      was twice as likely with new T1 contrast enhancing compared to new T2 lesions
      odds ratio (OR): 2.43, 95% confidence interval (CI): 2.00-2.96 vs OR: 1.26 (95%
      CI: 1.22-1.29). DMT change with new MRI lesions occurred most frequently with
      'injectable' DMTs. The probability of switching therapy was greater only after
      high-efficacy therapies became available in 2007 (after, OR: 1.43, 95% CI: 1.28
      1.59 vs before, OR: 0.98, 95% CI: 0.520-1.88). CONCLUSION: MS clinicians rely
      increasingly on MRI alone in their treatment decisions, utilizing low thresholds
      (1 new T2 lesion) for optimizing MS therapy. This signals a shift towards no
      evidence of disease activity (NEDA)-3 since high-efficacy therapies became
      available.

PMID- 30234434
TI  - Application of molecular framework-based data-mining method in the search for
      beta-secretase 1 inhibitors through drug repurposing.
AB  - Targeting beta-secretase 1, also known as beta-amyloid precursor protein-cleaving
      enzyme (BACE-1) for the inhibition of amyloid production, has been intensely
      studied in the last decades in the search for stopping Alzheimer's disease (AD)
      progression. The chances of finding a druggable BACE-1 inhibitor may be increased
      by drug repurposing, as this kind of molecules already fulfil certain
      requirements needed for further advancement. The study describes the development
      and application of a data-mining method based on molecular frameworks and
      descriptor values of tested BACE-1 inhibitors, suitable for filtering large
      compound databases, in order to find molecules with high potency against this
      protease. A total of 465 compounds extracted from the literature, tested against
      BACE-1, were analysed for finding molecular descriptor values and frameworks that
      ensure a high probability of strong inhibition. Resulting conclusions were used
      for filtering DrugBank database, containing ~8700 approved and experimental
      drugs, obtaining 26 structures characterized by four major Bemis-Murcko
      frameworks: 2-[3-(2-cyclohexylethyl)cyclohexyl]-decahydronaphthalene, 3-(2
      cyclohexylethyl)-1,1'-bi(cyclohexane), [5-(cyclohexylmethyl)-8
      cyclopentyloctyl]cyclohexane and (3-cyclohexylcyclopentyl)cyclohexane. The
      compounds were further studied by molecular docking using the structure of the
      closed form of the enzyme, which revealed seven compounds already involved in
      trials targeting BACE-1 inhibition, confirming the method's specificity. The
      compounds that afforded the best binding energies were DB06925 (tyrosine-protein
      kinase inhibitor), DB12285 (Verubecestat) and DB08899 (Enzalutamide). Moreover,
      docking results indicated several other molecules with high in silico inhibitory
      potency that can be further studied for developing a potential treatment for AD.
      Communicated by Ramaswamy H. Sarma.

PMID- 30234435
TI  - Impact of a Novel Surgical Wound Protection Device on Observed versus Expected
      Surgical Site Infection Rates after Colectomy Using the National Surgical Quality
      Improvement Program Risk Calculator.
AB  - BACKGROUND: Surgical site infection (SSI) remains a persistent and morbid problem
      in colorectal surgery. A novel surgical device that combines barrier surgical
      wound protection and continuous surgical wound irrigation was evaluated in a
      cohort of elective colorectal surgery patients. A retrospective analysis was
      performed comparing rates of SSI observed in a prospective cohort study with the
      predicted rate of SSI using the American College of Surgeons (ACS) National
      Surgical Quality Improvement Program (NSQIP) Risk Calculator. PATIENTS AND
      METHODS: A prospective multi-center study of colectomy patients was conducted
      using a study device for surgical site retraction and protection, as well as
      irrigation of the incision. Patients were followed for 30 days after the surgical
      procedure to assess for SSI. After completion of the study, patients'
      characteristics were inserted into the ACS-NSQIP Risk Calculator to determine the
      predicted rate of SSI for the given patient population and compared with the
      observed rate in the study. RESULTS: A total of 108 subjects were enrolled in the
      study. The observed rate of SSI in the prospective study using the novel device
      was 3.7% (4/108). The predicted rate of SSI in the same patient population
      utilizing the ACS-NSQIP Risk Calculator was estimated to be 9.5%. This
      demonstrated a 61% difference (3.7% vs. 9.5%, p = 0.04) in SSI from the NSQIP
      predicted rate with the use of the irrigating surgical wound protection and
      retraction device. CONCLUSIONS: These data suggest the use of a novel surgical
      wound protection device seems to reduce the rate of SSIs in colorectal surgery.

PMID- 30234436
TI  - Corrigendum.

PMID- 30234437
TI  - An In Vitro Comparative Study of Multisource Derived Human Mesenchymal Stem Cells
      for Bone Tissue Engineering.
AB  - Mesenchymal stem cells (MSCs) have been considered promising tools for tissue
      engineering and regenerative medicine. However, the optimal cell source for bone
      regeneration remains controversial. To better identify seed cells for bone tissue
      engineering, we compared MSCs from seven different tissues, including four from
      dental origins, dental pulp stem cells (DPSCs), periodontal ligament stem cells
      (PDLSCs), gingival MSCs (GMSCs), and dental follicle stem cells (DFSCs); two from
      somatic origins, bone marrow-derived MSCs (BM-MSCs) and adipose-derived stem
      cells (ADSCs); and one from birth-associated perinatal tissue umbilical cord
      (UCMSCs). We cultured the cells under a standardized culture condition and
      studied their biological characteristics. According to our results, these cells
      exhibited similar immunophenotype and had potential for multilineage
      differentiation. MSCs from dental and perinatal tissues proliferated more rapidly
      than those from somatic origins. Simultaneously, DPSCs and PDLSCs owned stronger
      antiapoptotic ability under the microenvironment of oxidative stress combined
      with serum deprivation. In respect to osteogenic differentiation, the two somatic
      MSCs, BM-MSCs and ADSCs, demonstrated the strongest ability for osteogenesis
      compared to PDLSCs and DFSCs, which were just a little bit weaker than the
      formers. However, GMSCs and UCMSCs were the most pertinacious ones to
      differentiate to osteoblasts. We also revealed that the canonical intracellular
      protein kinase-based cascade signaling pathways, including PI3K/AKT, MAPK/ERK,
      and p38 MAPK, possessed different levels of activation in different MSCs after
      osteoblast induction. Our conclusions suggest that PDLSCs might be a good
      potential alternative to BM-MSCs for bone tissue engineering.

PMID- 30234438
TI  - Retrospective Clinical and Microbiologic Analysis of Patients with Anorectal
      Abscess.
AB  - BACKGROUND: We conducted a clinical and microbiologic analysis of patients
      presenting with anorectal abscess. METHODS: A total of 505 adult patients
      presenting from January 2011 to December 2017 were analyzed retrospectively.
      Microbiologic data were available for 211 patients. RESULTS: The mean age at
      presentation was 39.5 (standard deviation 12.4) years, and 81.4% of the cohort
      were men. One hundred fifteen patients (22.8%) had diabetes mellitus, and 15
      patients (3.0%) had inflammatory bowel disease. There were 184 patients (36.4%)
      who required admission for more than 24 hours with a median length of stay of two
      days (interquartile range 2, 4) days. The most common microorganism was
      Escherichia coli (37.6%), followed by Bacteroides spp. (13.2%) and Streptococcus
      spp. (13.2%). Escherichia coli accounted for 34.9% of the microorganisms cultured
      from patients with diabetes mellitus followed by Streptococcus spp. (27%) and
      Klebsiella pneumoniae (20.6%). CONCLUSIONS: Escherichia coli is the most common
      micro-organism cultured from patients presenting with anorectal abscess. Despite
      an increase in community-acquired multi-resistant strains, our results show a low
      overall incidence of such isolate. Our study provides a large microbiologic
      sample of patients with anorectal abscess to expand the present knowledge of the
      etiology of a common surgical condition.

PMID- 30234439
TI  - Construction of Continuous Capillary Networks Stabilized by Pericyte-like
      Perivascular Cells.
AB  - Construction of small and continuous capillary networks is a fundamental
      challenge for the development of three-dimensional (3D) tissue engineering. In
      particular, to construct mature and stable capillary networks, it is important to
      consider interactions between endothelial cells and pericytes. This study aimed
      to construct stable capillary networks covered by pericyte-like perivascular
      cells, which maintain the lumen of small diameter similar to that of capillary
      structures in vivo. Vascular sprouting, capillary extension, and stabilization
      were investigated using a 3D angiogenesis model containing human umbilical vein
      endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) in a microfluidic
      device. A series of HUVEC:MSC ratios was tested; the ratio was found to be an
      important factor in the construction of capillary structures. We found that
      stable capillary networks that were covered by MSC-derived perivascular cells can
      be constructed at 1:1 HUVEC:MSC ratio. The constructed capillary networks had
      continuous lumens with <10-MUm diameter, which were maintained for at least 21
      days. This angiogenic process and basement membrane formation were regulated by
      HUVEC-MSC interactions.

PMID- 30234440
TI  - Around 90 degrees  Contact Angle of Dish Surface Is a Key Factor in Achieving
      Spontaneous Spheroid Formation.
AB  - Following the discovery of the primary culture of neural stem cells, the spheroid
      culture has been recognized as one of the selective culture methods for somatic
      stem cells. Since then, various methods were reported to generate spheroids,
      which can enrich the potent stem cell population. However, the fundamental
      factors affecting spheroid formation remain unclear. In this study, we focused on
      the surface property of the culture dishes, in particular, hydrophobicity.
      Primary mouse skin culture cells were prepared with conventional two-dimensional
      culture, and then, the cells were transferred to culture dishes with varying
      hydrophobicity, which was confirmed with the water contact angles. Of these, a
      culture dish possessing an almost 90 degrees  water contact angle was the only
      one that successfully exhibited spheroid formation. The spheroid formation was
      spontaneous, efficient, and stable. Since this outcome was achieved with a
      conventional culture medium with serum, but without any additives such as
      epidermal growth factor, basic fibroblast growth factor, and B27, the spheroid
      formation from this process was not affected by serum and was also not dependent
      on additives. The results from immunofluorescence and quantitative real-time
      polymerase chain reaction testing showed the expression of embryonic stem cell
      markers such as SSEA-1, SOX2, OCT4, and Nanog, which confirmed that the spheroids
      with this method are comparable to those from other methods. This outcome was
      reproducible and could be applied not only to skin-derived cells but also to oral
      mucosa-derived cells, cortical bone-derived cells, and 3T3 cells, also suggesting
      the generality and robustness of this phenomenon.

PMID- 30234441
TI  - Effect of electron beam sterilization on 3D printed PCL/beta-TCP scaffolds for
      bone tissue engineering.
AB  - 3D printing of composite materials such as polycaprolactone/beta-tricalcium
      phosphate (PCL/beta-TCP) enables the design and manufacturing of scaffolds with
      advanced geometries, along with improved physical and biological properties for
      large bone defect repair. Terminal sterilization of the scaffolds is inevitable
      for clinical applications. Electron beam (E-beam) is non-toxic, and can be used
      for sterilizing heat sensitive scaffolds by the use of high radiation dose in a
      short period of time. In this paper, we assessed the influence of E-beam
      sterilization on the properties of 3D printed PCL/beta-TCP scaffolds, focusing on
      the key physical and biological properties for bone tissue engineering. More
      specifically, we characterized the effect of a single dose E-beam sterilization
      (25kGy, ISO 11137) on surface morphology, hydrophilicity, degradation and
      mechanical properties of the scaffolds as well as in vitro biological responses.
      The results showed that E-beam irradiation did not alter the surface properties
      of scaffolds. A 14% increase in initial mechanical stiffness and strength of the
      scaffolds was observed after E-beam treatment. In addition, the E-beam treated
      scaffolds had 25% faster degradation. The PCL chains within the scaffolds had
      larger polydispersity after the E-beam irradiation that was indicative of a
      concurrent crosslinking and chain scission. Moreover, in vitro cell studies
      showed no influence of E-beam sterilization on viability, attachment,
      proliferation, and osteogenic differentiation of cells seeded on the PCL/beta-TCP
      scaffolds.

PMID- 30234442
TI  - Efficacy and Safety of Transnasal CoolStat Cooling Device to Induce and Maintain
      Hypothermia.
AB  - Targeted temperature management (TTM) is recommended as a standard of care for
      postcardiac arrest patients. Current TTM methods have significant limitations to
      be used in an ambulatory setting. We investigated the efficacy and safety of a
      novel noninvasive transnasal evaporative cooling device (CoolStatTM). Eleven
      Yorkshire pigs underwent hypothermia therapy using the CoolStat device. CoolStat
      induces evaporative cooling by blowing dehumidified ambient air over the nasal
      turbinates in a unidirectional fashion. CoolStat's efficacy and safety were
      assessed by applying different cooling strategies (groups A, B and C). In group A
      (efficacy study; n = 5, TTM for 8 hours), time to achieve brain target
      temperature (2 degrees C reduction from baseline), and the percentage of time in
      which the temperature ranged within +/-0.5 degrees C after reaching the target
      temperature were investigated. In the safety assessment (groups B and C), two
      worst-case therapy situations were reproduced: in group B (n = 3), continuous
      maximum air flow (65 L/min) was applied without temperature control and, in group
      C (n = 3), subjects underwent 24-hour TTM (prolonged therapy). Hemodynamic and
      respiratory parameters, nasal mucosa integrity (endoscopic assessment), and other
      therapy-related adverse effects were evaluated. Efficacy study: CoolStat cooling
      therapy successfully induced and sustained managed hypothermia in all subjects.
      Brain target temperature was achieved in 0.5 +/- 0.6 hours and kept within a +/
      0.5 degrees C range for the therapy duration (99.9% +/- 0.1%). All animals
      completed the safety studies. Maximum air flow (group B) and 24-hour (group C)
      therapies were well tolerated and no significant damage was observed on nasal
      mucosa for neither of the groups. CoolStat was able to efficiently induce and
      maintain hypothermia using unidirectional high flow of dry air into the nostrils
      of porcine models. CoolStat therapy was well tolerated and no damage to nasal
      mucosa was observed under either maximum air flow or prolonged therapy.

PMID- 30234444
TI  - Optimization of the Platelet-Rich Plasma Concentration for Mesenchymal Stem Cell
      Applications.
AB  - Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are promising tools
      for muscular-skeletal regeneration. However, increasing evidence has demonstrated
      controversial effects of PRP on the tissue regeneration. To obtain optimum PRP
      concentrations for MSC expansion and to accurately control osteogenic,
      adipocytic, and chondrogenic differentiation, MSCs were exposed to PRP alone or
      in combination with induction medium. We found that PRPs with the platelet
      concentration beyond 1500 * 109 pl/L were preferable to promote MSC
      proliferation. In addition, PRPs ranging from 200 * 109 to 3000 * 109 pl/L were
      capable of augmenting MSC osteogenesis, and PRP with 1500 * 109 pl/L was most
      effective for MSC osteogenic differentiation. Furthermore, PRPs in low platelet
      concentration range just slightly promoted MSC adipogenesis, and only when the
      platelet concentration was beyond 1800 * 109 pl/L, the promoted effects were
      evident. Moreover, PRP range from 1000 to 3000 * 109 pl/L significantly enhanced
      chondrogenesis of MSCs in the absence and presence of chondrogenic induction
      medium, and PRP with 2000 * 109 pl/L was more effective for MSC chondrogenesis.
      Furthermore, we explored the mechanisms of PRP-induced MSC differentiation,
      showing that the growth factors played a major role in this process while other
      unknown factors may also be involved in it. At last, we measured the levels of
      cytokines to learn that PRP treatment suppressed the secretion of interleukin
      1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha, but favored the
      production of IL-10 by MSCs. In summary, our findings demonstrated that PRPs with
      different concentrations of platelets exerted different effects on proliferation
      and differentiation of MSCs, which indicated that preparing appropriate PRPs may
      be a precise and efficient strategy for improving MSC-based tissue regeneration.

PMID- 30234443
TI  - A Perfusion Bioreactor System for Cell Seeding and Oxygen-Controlled Cultivation
      of Three-Dimensional Cell Cultures.
AB  - Bioreactor systems facilitate three-dimensional (3D) cell culture by coping with
      limitations of static cultivation techniques. To allow for the investigation of
      proper cultivation conditions and the reproducible generation of tissue
      engineered grafts, a bioreactor system, which comprises the control of crucial
      cultivation parameters in independent-operating parallel bioreactors, is
      beneficial. Furthermore, the use of a bioreactor as an automated cell seeding
      tool enables even cell distributions on stable scaffolds. In this study, we
      developed a perfusion microbioreactor system, which enables the cultivation of 3D
      cell cultures in an oxygen-controlled environment in up to four independent
      operating bioreactors. Therefore, perfusion microbioreactors were designed with
      the help of computer-aided design, and manufactured using the 3D printing
      technologies stereolithography and fused deposition modeling. A uniform flow
      distribution in the microbioreactor was shown using a computational fluid
      dynamics model. For oxygen measurements, microsensors were integrated in the
      bioreactors to measure the oxygen concentration (OC) in the geometric center of
      the 3D cell cultures. To control the OC in each bioreactor independently, an
      automated feedback loop was developed, which adjusts the perfusion velocity
      according to the oxygen sensor signal. Furthermore, an automated cell seeding
      protocol was implemented to facilitate the even distribution of cells within a
      stable scaffold in a reproducible way. As proof of concept, the human mesenchymal
      stem cell line SCP-1 was seeded on bovine cancellous bone matrix of 1 cm3 and
      cultivated in the developed microbioreactor system at different oxygen levels.
      The oxygen control was capable to maintain preset oxygen levels +/-0.5% over a
      cultivation period of several days. Using the automated cell seeding procedure
      resulted in evenly distributed cells within a stable scaffold. In summary, the
      developed microbioreactor system enables the cultivation of 3D cell cultures in
      an automated and thus reproducible way by providing up to four independently
      operating, oxygen-controlled bioreactors. In combination with the automated cell
      seeding procedure, the bioreactor system opens up new possibilities to conduct
      more reproducible experiments to investigate optimal cultivation parameters and
      to generate tissue-engineering grafts in an oxygen-controlled environment.

PMID- 30234445
TI  - Potential Usefulness of Filamentous Fungi to Prevent Zoonotic Soil-Transmitted
      Helminths.
AB  - The usefulness of a strategy involving the biological control of soil-transmitted
      helminths (STHs) with zoonotic potential is tested. A blend of spores of two
      filamentous fungi, Mucor circinelloides and Duddingtonia flagrans, was provided
      to one group (G-2) of puppies (five Griffon bleu de Gascogne and five Gascon
      Saintongeois) shedding eggs of Toxocara canis, Toxascaris leonina, Trichuris
      vulpis, and Ancylostoma caninum. Other identical group (G-1) remained without
      spores. Fecal samples were collected daily and divided into two portions, one
      sample was immediately analyzed by the flotation test and the other was examined
      28 days later. Viability of eggs of T. canis, T. leonina, and T. vulpis in fecal
      pats was ascertained by microscopic examination; the numbers of larvae of A.
      caninum were assessed in each group. In the feces of G-2, spores of both fungi
      were observed 1 day after beginning the assay. Viability of eggs of T. canis was
      reduced by 57%, T. leonina by 61% and T. vulpis by 53% in the fecal pats of G-2,
      and by 87%, 92%, and 85%, respectively, in G-1. The numbers of third-stage larvae
      of A. caninum were 59% lower in G-2 than that in G-1. By considering the results
      obtained and the absence of adverse effects in the puppies of G-2, it is
      concluded that the presence of the filamentous fungi in the feces has a high
      potential to avoid the transmission of these parasites. Further studies are in
      progress to determine the appropriate way of administration to pets.

PMID- 30234446
TI  - Leadership in interprofessional health and social care teams: a literature
      review.
AB  - Purpose The purpose of this study is to review evidence on the nature of
      effective leadership in interprofessional health and social care teams.
      Design/methodology/approach A critical review and thematic synthesis of research
      literature conducted using systematic methods to identify and construct a
      framework to explain the available evidence about leadership in interprofessional
      health and social care teams. Findings Twenty-eight papers were reviewed and
      contributed to the framework for interprofessional leadership. Twelve themes
      emerged from the literature, the themes were: facilitate shared leadership;
      transformation and change; personal qualities; goal alignment; creativity and
      innovation; communication; team-building; leadership clarity; direction setting;
      external liaison; skill mix and diversity; clinical and contextual expertise. The
      discussion includes some comparative analysis with theories and themes in team
      management and team leadership. Originality/value This research identifies some
      of the characteristics of effective leadership of interprofessional health and
      social care teams. By capturing and synthesising the literature, it is clear that
      effective interprofessional health and social care team leadership requires a
      unique blend of knowledge and skills that support innovation and improvement.
      Further research is required to deepen the understanding of the degree to which
      team leadership results in better outcomes for both patients and teams.

PMID- 30234447
TI  - Can Lean Six Sigma be used to reduce medication errors in the health-care sector?
AB  - Purpose The purpose of this paper is to present the implementation of Lean Six
      Sigma (LSS) to reduce medication errors, by using four case examples. The paper
      will also suggest appropriate Lean and Sigma tools to improve the medication
      process. Design/methodology/approach The authors critically analyze four case
      examples that used LSS projects, to demonstrate the approach, benefits, success
      factors and lessons learnt. Findings LSS is a powerful process improvement
      methodology that could be applied by health-care sectors to reduce medication
      errors, increase patient safety and reduce operational costs. Common Lean and Six
      Sigma tools play a significant role in improving and sustaining the medication
      process. Practical implications It is necessary for the project team to select
      the most appropriate LSS tools to address medication process problems. Adoption
      of a LSS roadmap could help health-care organizations in the successful
      implementation of LSS. Originality/value The paper is valuable for health-care
      professionals seeking to reduce errors in the medication process or other
      processes that need to be improved.

PMID- 30234448
TI  - Sensemaking and cognitive shifts - learning from dissemination of a National
      Quality Register in health care and elderly care.
AB  - Purpose The purpose of this study is to examine and establish how sensemaking
      develops among a group of external change agents (ECAs) engaged to disseminate a
      national quality register nationwide in Swedish health care and elderly care. To
      study the emergent sensemaking, the theoretical concept of cognitive shift has
      been used. Design/methodology/approach The data collection method included
      individual semi-structured interviews, and two sets of interviews (initial
      sensemaking and renewed sensemaking) have been conducted. Based on a typology
      describing how ECAs interpret their work, structural analyses and comparisons of
      initial and renewed sensemaking are made and illuminated in spider diagrams. The
      data are then analyzed to search for cognitive shifts. Findings The ECAs'
      sensemaking develops. Three cognitive shifts are identified, and a new kind of
      issue-related cognitive shift, the outcome-related cognitive shift, is suggested.
      For the ECAs to customize their work, they need to be aware of how they interpret
      their own work and how these interpretations develop over time. Originality/value
      The study takes a novel view of the interrelated concepts of sensemaking and
      sensegivers and points out the cognitive shifts as a helpful theoretical concept
      to study how sensemaking develops.

PMID- 30234449
TI  - Factors that foster or prevent sense of belonging among social and health care
      managers.
AB  - Purpose The purpose of this study is to identify factors that foster or prevent
      sense of belonging among frontline and middle managers in social and health-care
      services in Finland. Design/methodology/approach The data have been collected
      among social and health-care managers ( n = 135; 64 per cent nursing managers)
      through two open-ended questions in a questionnaire concerning sense of
      community. The results of the open-ended questions have been analyzed using
      qualitative content analysis. Findings Among managers, six categories of factors
      that foster sense of belonging (open interaction, effective conversation culture,
      support and encouragement, common values, a shared vision of the work and its
      objectives and structure of leadership) and five categories of factors that
      prevent sense of belonging (negative work atmosphere, lack of common time,
      structural solutions in the organization, problems that occur in the
      organizational level and problems related to leadership and management) have been
      identified. Practical implications The resulting information can be used to
      develop sense of belonging among managers at all levels of organization
      (horizontal and vertical). Originality/value Paying attention to the quantity and
      quality of interaction and to structural solutions in the organization can affect
      the sense of belonging among frontline managers and middle managers.

PMID- 30234450
TI  - Prospective sensemaking of a national quality register in health care and elderly
      care.
AB  - Purpose The purpose of this paper is to examine how external change agents (ECAs)
      engaged to disseminate a national quality register (NQR) called Senior alert
      nationwide in the Swedish health care and elderly care sectors interpret their
      work. To study this, sensemaking theories are used. Design/methodology/approach
      This is a qualitative inductive interview study including eight ECAs. To analyze
      the data, a thematic analysis is carried out. Findings Well-disseminated NQRs
      support health care organizations' possibility to work with quality improvement
      and to improve care for patient groups. NQRs function as artifacts that can
      influence how health care professionals make sense of their work. In this paper,
      a typology depicting how the ECAs make sense of their dissemination work has been
      developed. The ECAs are engaged in prospective sensemaking. They describe their
      work as being about creating future good results, both for patients and
      affiliated organizations, and they can balance different quality aspects.
      Originality/value The number of NQRs increased markedly in Sweden and elsewhere,
      but there are few reports on how health care professionals working with the
      registers interpret their work. The use of ECAs to disseminate NQRs is a novel
      approach. This paper describes how the ECAs are engaged in prospective
      sensemaking - an under-researched perspective of the sensemaking theory.

PMID- 30234451
TI  - Quality improvement in curriculum development.
AB  - Purpose There is a growing emphasis on teaching patient safety principles and
      quality improvement (QI) processes in medical education curricula. This paper
      aims to present how the Faculty of Medicine at Memorial University of
      Newfoundland engaged medical students in quality improvement during their recent
      curriculum renewal process. Design/methodology/approach In the 2013-2014 academic
      year, the Faculty of Medicine at Memorial University of Newfoundland launched an
      undergraduate medical education curriculum renewal process. This presented a
      unique opportunity to teach quality improvement by involving students in the
      ongoing development and continuous improvement of their undergraduate curriculum
      through the implementation of quality circles and other related QI activities.
      Findings The authors' experience shows that implementing QI processes is
      beneficial in the medical education environment, particularly during times of
      curriculum redesign or implementation of new initiatives. Originality/value
      Student engagement and participation in the QI process is an excellent way to
      teach basic QI concepts and improve curriculum program outcomes.

PMID- 30234452
TI  - The influence of leadership behavior, organizational commitment, organizational
      support, subjective career success on organizational readiness for change in
      healthcare organizations.
AB  - Purpose The purpose of this study is to investigate the influence of leadership
      behavior, organizational commitment, organizational support and subjective career
      success on organizational readiness for change in the healthcare organizations.
      The authors want to determine if nurses who had higher levels of organizational
      commitment, organizational support and subjective career success relationships
      were more open and prepared for change. Design/methodology/approach Cross
      sectional, descriptive-correlational survey design was conducted using self
      reported questionnaires to collect data from registered nurses. Findings The
      subjective career success was the strongest predictors ( beta = 0.36, p < 0.001)
      followed by leadership behavior ( beta = -0.19, p = 0.03) and participants' age (
      beta = -0.13, p = 0.049). Research limitations/implications This study highlights
      the influence of leadership behavior, organizational commitment, organizational
      support and subjective career success on the organizational readiness for change
      in healthcare organizations. Therefore, this study forms baseline data for future
      local and national studies. Moreover, it will strengthen the research findings if
      future research includes a qualitative approach that explores other healthcare
      professionals regarding readiness for organizational change. Practical
      implications This study provides information to policymakers and healthcare
      leaders who seek to improve management and leadership skills and respond to
      organizational change efforts. Social implications It is important to know the
      extent to which healthcare professionals, especially nurses, understand how the
      influence of organizational support and organizational commitment on
      organizational readiness for change, as well as why specific leadership behavior
      and subjective career success, is important in implementing the change.
      Originality/value This study examined the nurses' readiness for change in
      hospitals. Organizational readiness for change could occur in situations where
      nurses can exert extra efforts at work because of leaders' behaviors and the
      relationship between nurses and the institution.

PMID- 30234453
TI  - Developing health leadership with Health LEADS Australia.
AB  - Purpose Leadership, and leadership development, in health and human services is
      essential. This review aims to draw conclusions from practice within the
      Australian context. Design/methodology/approach This review is an overview of
      health leadership development in Australia, with a particular focus on the
      implementation of the national health leadership framework, Health LEADS
      Australia (HLA). Findings Since its inception, the HLA has influenced the
      development of health leadership frameworks across the Australian states and
      territories. Both the National Health Leadership Collaboration and individuals
      with "boundary-spanning" roles across state government and the university sector
      have contributed to the development of collaborative online communities of
      practice and professional networks. Innovation has also been evident as the HLA
      has been incorporated into existing academic curricula and new professional
      development offerings. Ideas associated with distributed leadership, integral to
      the HLA, underpin both sets of actions. Practical implications The concept of a
      national health leadership framework has been implemented in different ways
      across jurisdictions. The range of alternative strategies (both collaborative and
      innovative) undertaken by Australian practitioners provide lessons for practice
      elsewhere. Originality/value This article adds to the body of knowledge
      associated with policy implementation and provides practical recommendations for
      the development and promotion of health leadership development programmes.

PMID- 30234454
TI  - Career path from a dentist to a leader.
AB  - Purpose The purpose of this paper was to study the career paths of leaders with a
      career background as a dentist from basic degree to chief or executive leadership
      positions and individual factors that influenced their decisions.
      Design/methodology/approach Semi-structured interview and a questionnaire were
      used to study 13 leaders using the structure of Edgar Schein's career anchor
      interview and career orientation inventory questionnaire. Theory-driven content
      analysis was used to analyze the data according to themes which included career
      paths, factors associated with job and career changes and thoughts about future
      careers. Findings Three different career path types were identified: Progressives
      (Type A), By chance (Type B), and Enthusiasts (Type C). The main motives were:
      the Progressives' goal orientation to proceed to higher leadership positions, the
      By chance group's job and even career changing by taking a chance on an
      interesting possibility that comes their way and the Enthusiasts' willingness to
      make a difference and search for possibilities to change things. The most
      important career anchor was "pure challenge" among the Progressives and By chance
      groups and "general managerial competence" among the Enthusiasts.
      Originality/value Studies on personal factors associating with career paths in
      health care are scarce and similarly leaders with a dentist background are less
      studied, even though leadership could be an excellent career choice for a
      dentist. Different individuals can have varied motives and career paths toward
      executive positions. Because of the multi-professional functions in health care,
      organizations could benefit from having leaders with different expertise
      backgrounds.

PMID- 30234455
TI  - Organisational learning.
AB  - Purpose The understanding of "organisations" has changed fundamentally from
      seeing them as concrete entities to viewing them as communities of meaning.
      Mature adults in healthcare learn best when addressing pressing problems in
      company of their peers. Healthcare is unlike other sectors because of the
      emotional labour which is part of the experience of clinical staff. Absorptive
      capacity offers a conceptual model for viewing organisational learning and the
      encouragement of systemic eloquence can be enabled through a variety of
      approaches, provided they are designed and delivered as part of a well-thought
      through approach to developing local absorptive capacity.
      Design/methodology/approach This is a viewpoint paper. Findings Healthcare
      differs from other sectors. Organisational learning can be enabled by a range of
      approaches, but these need to be sensitive to local circumstances.
      Originality/value The paper asserts that healthcare is unlike other sectors
      because of emotional labour on the part of clinical staff. It maintains that
      organisations are communities of meaning, rather than concrete entities. Systemic
      eloquence can be enhanced by the concept of absorptive capacity, applied in local
      contexts.

PMID- 30234456
TI  - Incorporating sustainability in small health-care facilities: an integrated
      model.
AB  - Purpose It is challenging for small health-care facilities to implement changes
      when human and financial resources are limited for day-to-day operations. This
      paper aims to propose an integrated model for small- and medium-sized health-care
      facilities to integrate sustainability in their day-to-day operations, which have
      been derived from the leadership and change theories. Design/methodology/approach
      Drawing on previous research on leadership and change theories, the paper first
      critically reviewed the approaches to implementing changes and how applicable
      they are in the context of small- and medium-sized health-care facilities. Next,
      it proposes an integrated model with an execution plan. Findings The first part
      of the paper discusses how either the planned approach or emergent approach for
      change may fail in facilitating the implementation of sustainable initiatives, as
      incorporating sustainability into operations require both leadership of change
      and open learning systems. The second part outlines the four-phase combined
      approach, which includes phases of "exploration", "planning", "action" and
      "integration", and discusses how change readiness is ensured through such
      approach. Practical implications The authors propose an integrated model as a
      framework for integrating sustainability into the operations of small health-care
      facilities. The clearest possible steps at various phases are proposed. Potential
      barriers and risks are highlighted and the coping strategies proposed to maximise
      the chance of successfully transforming organisations. Originality/value Applying
      the "how to" ideas based on the integrated model for change management will help
      leaders of health-care facilities gradually integrate sustainability into their
      day-to-day operations.

PMID- 30234457
TI  - Dicentric Dose Estimates for Patients Undergoing Radiotherapy in the RTGene Study
      to Assess Blood Dosimetric Models and the New Bayesian Method for Gradient
      Exposure.
AB  - The RTGene study was focused on the development and validation of new
      transcriptional biomarkers for prediction of individual radiotherapy patient
      responses to ionizing radiation. In parallel, for validation purposes, this study
      incorporated conventional biomarkers of radiation exposure, including the
      dicentric assay. Peripheral blood samples were taken with ethical approval and
      informed consent from a total of 20 patients undergoing external beam
      radiotherapy for breast, lung, gastrointestinal or genitourinary tumors. For the
      dicentric assay, two samples were taken from each patient: prior to radiotherapy
      and before the final fraction. Blood samples were set up using standard methods
      for the dicentric assay. All the baseline samples had dicentric frequencies
      consistent with the expected background for the normal population. For blood
      taken before the final fraction, all the samples displayed distributions of
      aberrations, which are indicative of partial-body exposures. Whole-body and
      partial-body cytogenetic doses were calculated with reference to a 250-kVp X-ray
      calibration curve and then compared to the dose to blood derived using two newly
      developed blood dosimetric models. Initial comparisons indicated that the
      relationship between these measures of dose appear very promising, with a
      correlation of 0.88 ( P = 0.001). A new Bayesian zero-inflated Poisson finite
      mixture method was applied to the dicentric data, and partial-body dose estimates
      showed no significant difference ( P > 0.999) from those calculated by the
      contaminated Poisson technique. The next step will be further development and
      validation in a larger patient group.

PMID- 30234458
TI  - In Vitro Radiobiological Advantages of Hypofractionation Compared with
      Conventional Fractionation: Early-Passage NSCLC Cells are Less Aggressive after
      Hypofractionation.
AB  - Hypofractionated radiotherapy is a new and highly effective mode of radiation
      therapy. For this study we used biologically equivalent dose (BED), the dose
      required to give the same log cell kill as the schedule being studied. BED has
      been widely accepted to transform its dose to conventionally fractionated ones.
      However, actual differential effects beyond the clone-forming ability between
      hypofractionation and conventional radiation treatment remain unknown. We
      hypothesize that hypofractionation has some advantages over conventional
      treatment in in vitro radiobiology, excluding influences of the tumor
      microenvironment in angiogenesis and potential immune-stimulatory effects. For
      this study, two non-small cell lung cancer (NSCLC) cell lines with different
      alpha/beta values were chosen: A549 (alpha/beta = 12.4) and H460 (alpha/beta =
      2.95). We designed the following two fractionation regimens with equal BED: A549
      HRT (10 Gy/1 fraction) and A549-CRT (16 Gy/8 fractions) as well as H460-HRT (10
      Gy/1 fraction) and H460-CRT (26 Gy/13 fractions). After irradiation, we performed
      cell counting, MTT assay, flow cytometry analysis of apoptosis and cell cycle,
      immunocytofluorescence of gamma-H2AX and Hoechst 33258, and senescence-associated
      beta-galactosidase assay to identify differential effects. Glucose consumption
      and lactic acid production per cell were tested using glucose and lactate assays.
      Two weeks postirradiation, we collected early-passage cells of the colony cells
      after both conventional and fractionated irradiations for further investigation.
      Then, we used the side population (SP) assay, cell-counting assay and Transwell
      assay to test the proliferation and invasion capability, the MTT assay to
      identify the drug resistance of cisplatin, pemetrexed and docetaxel, the Western
      blot assay to test the stem cell-related proteins of NANOG, CD133, OCT4, SOX2,
      BMI1 and KLF4. After irradiation, the total cell count and cell viability in both
      cell lines gradually decreased in a similar manner. However, more senescent,
      necrotic cells and apoptotic cells were found in the conventionally-treated cells
      at an early time point postirradiation. Contrarily, a higher percentage of G2/M
      cell cycle arrest and more gamma-H2AX foci were found in the cell lines that
      received hypofractionated treatment. Glucose consumption and lactic acid
      production per cell were lower in the cell lines that received hypofractionated
      irradiation. Early-passage cells in the conventional-treated cell line showed
      more SP cells with higher expressions of NANOG, OCT4 and BMI1 proteins. Early
      passage cells in the conventional-treated cell line also revealed higher
      proliferative ability, drug resistance and invasion ability. Although we detected
      some radiobiological differences between the two fractionation treatments, there
      was no obvious advantage for hypofractionation in the early days postirradiation.
      However, there were some advantages for hypofractionation compared to
      conventional treatment in early-passage cells in vitro, which may partially
      contribute to its clinical advantages. Moreover, the damage to healthy tissue
      should also be addressed to fully elucidate the implications of radiotherapy
      addressed in this work.

PMID- 30234459
TI  - Zebrabase: An Intuitive Tracking Solution for Aquatic Model Organisms.
AB  - Small fish species, such as zebrafish and medaka, are increasingly gaining
      popularity in basic research and disease modeling as a useful alternative to
      rodent model organisms. However, the tracking options for fish within a facility
      are rather limited. In this study, we present an aquatic species tracking
      database, Zebrabase, developed in our zebrafish research and breeding facility
      that represents a practical and scalable solution and an intuitive platform for
      scientists, fish managers, and caretakers, in both small and large facilities.
      Zebrabase is a scalable, cross-platform fish tracking database developed
      especially for fish research facilities. Nevertheless, this platform can be
      easily adapted for a wide variety of aquatic model organisms housed in tanks. It
      provides sophisticated tracking, reporting, and management functions that help
      keep animal-related records well organized, including a QR code functionality for
      tank labeling. The implementation of various user roles ensures a functional
      hierarchy and customized access to specific functions and data. In addition,
      Zebrabase makes it easy to personalize rooms and racks, and its advanced
      statistics and reporting options make it an excellent tool for creating periodic
      reports of animal usage and productivity. Communication between the facility and
      the researchers can be streamlined by the database functions. Finally, Zebrabase
      also features an interactive breeding history and a smart interface with advanced
      visualizations and intuitive color coding that accelerate the processes.

PMID- 30234460
TI  - Induced Pluripotent Stem Cell Elimination in a Cell Sheet by Methionine-Free and
      42 degrees C Condition for Tumor Prevention.
AB  - Pluripotent stem cells, including induced pluripotent stem (iPS) cells, are
      promising cell sources for regenerative medicine to replace injured tissues, and
      tissue engineering technologies enable engraftment of functional iPS cell-derived
      cells in vivo for prolonged periods. However, the risk of tumor formation is a
      concern for the use of iPS cells. Bioengineered tissues provide a suitable
      environment for cell survival, which requires vigorous efforts to eliminate
      remaining iPS cells and prevent tumor formation. We recently reported three iPS
      cell elimination strategies, including methionine-free medium, TRPV1 activation
      through 42 degrees C cultivation, and dinaciclib, a cyclin-dependent kinase 1/9
      inhibitor. However, it remains unclear how many iPS cells in bioengineered
      tissues can be eliminated using these strategies alone or in combination, as well
      as the mode of subsequent tumor prevention. In the present study, we found that 2
      days of cultivation at 42 degrees C sufficiently eliminated 1 * 102 iPS cells in
      fibroblast sheets and prevented tumor formation. After screening for suitable
      combinations of these strategies based on Lin28 expression in co-cultures of
      fibroblasts and 1 * 104 iPS cells, we found that 1 day of cultivation at 42
      degrees C in methionine-free culture medium with or without dinaciclib remarkably
      decreased Lin28 expression and prevented tumor formation. Furthermore, these
      culture strategies did not affect spontaneous beating or the cell number of human
      iPS cell-derived cardiomyocytes. These quantitative findings may contribute to
      decreasing tumor formation risk and development of regenerative medicine using
      iPS cells.

PMID- 30234461
TI  - Bacterial Distribution and Risk Factors of Nosocomial Blood Stream Infection in
      Neurologic Patients in the Intensive Care Unit.
AB  - OBJECTIVE: To investigate the risk factors and analyze the distribution of
      pathogens to provide a basis for the prevention of nosocomial blood stream
      infections (BSI) and reduce the incidence and mortality of nosocomial BSI in
      neurologic patients. PATIENTS AND METHODS: A retrospective chart review of
      neurologic patients admitted to an adult intensive care unit from January 2012 to
      December 2017 was conducted. Every positive blood culture, clinical demographic,
      microbiologic and laboratory result, as well as 28-day outcome data, were
      compiled on a data collection sheet. The clinical significance of each isolate
      was determined; in addition, the antimicrobial susceptibilities of causative
      pathogens and the most likely source were recorded. RESULTS: During the five-year
      study period, there were 121 nosocomial BSI yielding 151 isolates in 404
      neurologic patients. Eighty-one percent of nosocomial BSI were monomicrobial.
      Gram-positive organisms caused 67.9% of these BSI, gram-negative organisms caused
      32.1%, and fungi caused 0.8%. The crude incidence rate was approximately 29.9%,
      and the mortality of nosocomial BSI was as high as 29.8%. Intravascular lines
      were the most common source of nosocomial BSI (79.3%). The most common organisms
      causing BSI were coagulase-negative staphylococci (CoNS; 44.6% of isolates),
      Staphylococcus aureus (17.4%), Klebsiella species (11.5%), and Acinetobacter spp.
      (11.5%). Multivariable regression analysis revealed that the use of antibiotic
      agents in the 90 days prior (odds ratio [OR], 5.81; 95% confidence interval [CI],
      3.18-10.62; p = 0.001), brain trauma (OR, 0.28; 95% CI, 0.15-0.51; p = 0.001),
      and transfusion (OR, 3.02; 95% CI, 1.45-6.29; p = 0.001) were significant
      predictors of nosocomial BSI. CONCLUSIONS: The incidence and mortality of
      nosocomial BSI were high in our neurologic patients. Strictly aseptic operations,
      hand hygiene, and reasonable use of transfusions and antibiotic agents are
      effective measures to prevent nosocomial BSI.

PMID- 30234462
TI  - Different Culture Times Affect MicroRNA Cargo in Equine Amniotic Mesenchymal
      Cells and Their Microvesicles.
AB  - Conditioned medium (CM) and microvesicles (MVs) are produced using different
      protocols: CM is collected following 12-96 h of cell culture without renewal of
      tissue culture medium, while MVs are collected after overnight cell culture. For
      future comparative studies in regenerative medicine looking at the efficacy of CM
      and MVs, it is important to understand how the quality of cell secretions is
      affected by culture. The aim of this study was to evaluate whether the duration
      of culturing influences the micro-RNAs (miRNAs) cargo of equine amniotic
      mesenchymal cells (AMCs) and their MVs. The analysis identified 990 miRNAs. After
      one night, there were 347 differently expressed (DE)-miRNAs between MVs and
      cells, whereas after four nights there were 359. About 58.3% of the DE-miRNAs
      were shared between samples produced under the two conditions. The comparison
      between miRNA content in AMC cells cultured for one night versus four nights
      showed eight DE-Equus caballus (eca)-miRNAs, which target genes were involved in
      immune response to external stimulus, inflammatory response, and production of
      reactive oxygen species. Comparing MVs isolated from one or four nights, four DE
      miRNAs that target genes regulating cell cycle progression and production of
      reactive oxygen species were found, but only eca-miR-214 was enriched in the MVs
      after four nights. In conclusion, after 4 days of cell culture, the profile of
      AMC miRNAs was altered, indicating a probable phenotypic transition versus a new
      cell culture environment and aging. After this time, MVs accumulated eca-miR-214,
      which may help cells survive or adapt to new culture conditions.

PMID- 30234463
TI  - The preventable proportion of healthcare-associated infections 2005-2016:
      Systematic review and meta-analysis.
AB  - OBJECTIVE: The preventable proportion of healthcare-associated infections (HAIs)
      may decrease over time as standards of care improve. We aimed to assess the
      proportion of HAIs prevented by multifaceted infection control interventions in
      different economic settings. METHODS: In this systematic review and meta
      analysis, we searched OVID Medline, EMBASE, CINAHL, PubMed, and The Cochrane
      Library for studies published between 2005 and 2016 assessing multifaceted
      interventions to reduce catheter-associated urinary tract infections (CAUTIs),
      central-line-associated bloodstream infections (CLABSIs), surgical site
      infections (SSIs), ventilator-associated pneumonia (VAP), and hospital-acquired
      pneumonia not associated with mechanical ventilation (HAP) in acute-care or long
      term care settings. For studies reporting raw rates, we extracted data and
      calculated the natural log of the risk ratio and variance to obtain pooled risk
      ratio estimates. RESULTS: Of the 5,226 articles identified by our search, 144
      studies were included in the final analysis. Pooled incidence rate ratios
      associated with multifaceted interventions were 0.543 (95% confidence interval
      [CI], 0.445-0.662) for CAUTI, 0.459 (95% CI, 0.381-0.554) for CLABSI, and 0.553
      (95% CI, 0.465-0.657) for VAP. The pooled rate ratio was 0.461 (95% CI, 0.389
      0.546) for interventions aiming at SSI reduction, and for VAP reduction
      initiatives, the pooled rate ratios were 0.611 (95% CI, 0.414-0.900) for before
      and-after studies and 0.509 (95% CI, 0.277-0.937) for randomized controlled
      trials. Reductions in infection rates were independent of the economic status of
      the study country. The risk of bias was high in 143 of 144 studies (99.3%).
      CONCLUSIONS: Published evidence suggests a sustained potential for the
      significant reduction of HAI rates in the range of 35%-55% associated with
      multifaceted interventions irrespective of a country's income level.

PMID- 30234464
TI  - Trait Mindfulness and Wellness in Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is a chronic, progressive, autoimmune, neurodegenerative
      disorder that can interfere with physical and psychological functioning,
      negatively affecting health-related quality of life (HRQoL). Fostering
      mindfulness may mitigate the negative consequences of MS on HRQoL. The
      relationship between mindfulness, mood and MS-related quality of life was
      investigated. In total, 52 individuals with MS completed questionnaires to
      examine the relationship between trait mindfulness and wellness. Higher levels of
      trait mindfulness were associated with better HRQoL, lower depression and
      anxiety, lower fatigue impact and fewer perceived cognitive deficits. Mindfulness
      interventions have the potential to enhance wellness in those living with MS.

PMID- 30234465
TI  - Regression of Degenerative Retro-Odontoid Pseudotumour Treated in a Collar.

PMID- 30234466
TI  - Hypertrophic Olivary Degeneration Following Listerial Rhombencephalitis.

PMID- 30234467
TI  - Subdural Empyema.

PMID- 30234468
TI  - The Positive Predictive Value of Onconeural Antibody Testing: A Retrospective
      Review.
AB  - Paraneoplastic syndromes (PNS) are immune-mediated neurologic diseases that occur
      as an indirect effect of malignancy, and can be challenging to diagnose.
      Onconeural antibodies have a greater than 95% association with cancer, and their
      presence in a patient with neurologic symptoms is reportedly highly indicative of
      PNS. However, we performed a single-centre retrospective review to determine the
      positive predictive value of onconeural antibody testing, and found it to be
      concerningly low (39%). Recognising the limitations of onconeural antibody
      testing is critical to ensure accurate test interpretation, avoid unnecessary
      repeated malignancy screening and prevent the use of potentially hazardous
      immunotherapy.

PMID- 30234469
TI  - Digital Subtraction Angiography for CT Angiogram Negative Haemorrhages.
AB  - BACKGROUND: In patients with subarachnoid haemorrhage (SAH) and a negative
      finding on CT angiography (CTA), further imaging with digital subtraction
      angiography (DSA) is commonly performed to identify the source of bleeding. The
      purpose of this study was to investigate whether negative findings on CTA can
      reliably exclude aneurysms in patients with acute SAH. METHODS: This
      retrospective study identified all DSAs performed between August 2010 and July
      2014 within our institution. CT angiography was performed with a 64-section
      multidetector row CT scanner. Only DSAs from patients with confirmed SAH and a
      negative CTA result were included in the final analyses. A fellowship-trained
      neuroradiologist reviewed the imaging results. RESULTS: Of the 857 DSAs, 50
      (5.83%) were performed in 35 patients with CTA-negative SAH. Of the 35 patients,
      three (8.57%) had positive findings on the DSA. In one patient, suspicious
      dissection of the extra- and intra-cranial segment of the right vertebral artery
      could not be confirmed even in retrospect. In the second patient, the suspicious
      finding of tiny protuberance from the left paraclinoid internal carotid artery
      (ICA) on DSA did not change on follow-up and did not change patient's management.
      The third patient had a posterior inferior cerebellar artery aneurysm, which was
      not seen on the initial CTA owing to the incomplete coverage of the head on the
      CTA. CONCLUSION: In patients with SAH, negative findings on a technically sound
      CTA are reliable in ruling out aneurysms in any pattern of SAH or no blood on CT.
      Our observations need to be confirmed with larger prospective studies.

PMID- 30234470
TI  - Texture Analysis to Detect Cerebral Degeneration in Amyotrophic Lateral
      Sclerosis.
AB  - BACKGROUND: Evidence of cerebral degeneration is not apparent on routine brain
      MRI in amyotrophic lateral sclerosis (ALS). Texture analysis can detect change in
      images based on the statistical properties of voxel intensities. Our objective
      was to test the utility of texture analysis in detecting cerebral degeneration in
      ALS. A secondary objective was to determine whether the performance of texture
      analysis is dependent on image resolution. METHODS: High-resolution (0.5*0.5 mm2
      in-plane) coronal T2-weighted MRI of the brain were acquired from 12 patients
      with ALS and 19 healthy controls on a 4.7 Tesla MRI system. Image data sets at
      lower resolutions were created by down-sampling to 1*1, 2*2, 3*3, and 4*4 mm2.
      Texture features were extracted from a slice encompassing the corticospinal tract
      at the different resolutions and tested for their discriminatory power and
      correlations with clinical measures. Subjects were also classified by visual
      assessment by expert reviewers. RESULTS: Texture features were different between
      ALS patients and healthy controls at 1*1, 2*2, and 3*3 mm2 resolutions. Texture
      features correlated with measures of upper motor neuron function and disability.
      Optimal classification performance was achieved when best-performing texture
      features were combined with visual assessment at 2*2 mm2 resolution (0.851 area
      under the curve, 83% sensitivity, 79% specificity). CONCLUSIONS: Texture analysis
      can detect subtle abnormalities in MRI of ALS patients. The clinical yield of the
      method is dependent on image resolution. Texture analysis holds promise as a
      potential source of neuroimaging biomarkers in ALS.

PMID- 30234471
TI  - Canadian Assessment of Deep Brain Stimulation Access: The Canada Study.
AB  - BACKGROUND: The Canada Health Act requires reasonable access to all medically
      necessary therapies. No information is available to assess the current access to
      neuromodulation across Canada. This study quantifies the current rate of deep
      brain stimulation (DBS) for the entire country of Canada. Analyses were performed
      to determine whether there were differences in access based on provincial or
      territorial location, rural or non-rural region, or socioeconomic status.
      METHODS: All implanted DBS devices in Canada over a 2-year epoch (January 2015 to
      December 2016) were supplied by either Boston Scientific or Medtronic.
      Investigators received anonymized data from these companies, including patient
      age and home residence region. The 2016 Statistics Canada census data were used
      to determine the rate of DBS surgery and whether access was related to provincial
      location, rural versus non-rural region or socioeconomic status. RESULTS: A total
      of 722 patients were studied. The rate of DBS surgery for the entire country was
      ten per million population per year. Saskatchewan was significantly above (374%)
      the national average, whereas Quebec (40%) and Newfoundland & Labrador (32%) were
      significantly below the national average. No patients from the three territories
      received DBS. There were no significant differences in access from rural versus
      non-rural areas or in regions within provinces with different socioeconomic
      status. CONCLUSIONS: This is the first study to quantify all patients receiving
      DBS within an entire country. The current rate of DBS surgery within Canada is
      ten cases per million per year. Statistically significant regional differences
      were discovered and discussed.

PMID- 30234472
TI  - Neuromuscular Ultrasound: A New Tool in Your Toolbox.
AB  - Neuromuscular ultrasound is a rapidly evolving technique for diagnosing,
      monitoring and facilitating treatment of patients with muscle and nerve
      disorders. It is a portable point-of-care technology that is non-invasive,
      painless and without ionizing radiation. Ultrasound can visualize muscle texture
      alterations indicating dystrophy or denervation, changes in size and anatomic
      continuity of nerve fascicles, and its dynamic imaging capabilities allow
      capturing of contractions and fasciculations. Ultrasound can also provide real
      time guidance for needle placement, and can sometimes make a diagnosis when
      electromyography is not tolerated or not informative anymore. This review will
      focus on the technical and practical aspects of ultrasound as an imaging
      technique for muscles and nerves. It will discuss basic imaging principles,
      hardware and software setup, and provide examples of ultrasound use for
      visualizing muscle and nerve abnormalities with accuracy and confidence. The
      review is intended as a practical "how-to" guide to get started with
      neuromuscular ultrasound in daily practice.

PMID- 30234473
TI  - Nothing Ventured, Nothing Gained? Navigating Disease-Modifying Treatment in
      Multiple Sclerosis.

PMID- 30234474
TI  - Chronic Myelomonocytic Leukemia Mimicking Invasive Fungal Rhinosinusitis.

PMID- 30234475
TI  - Mycophenolate Mofetil-Induced Status Epilepticus.

PMID- 30234477
TI  - Better together: the role of IFIT protein-protein interactions in the antiviral
      response.
AB  - The interferon-induced proteins with tetratricopeptide repeats (IFITs) are a
      family of antiviral proteins conserved throughout all vertebrates. IFIT1 binds
      tightly to non-self RNA, particularly capped transcripts lacking methylation on
      the first cap-proximal nucleotide, and inhibits their translation by out
      competing the cellular translation initiation apparatus. This exerts immense
      selection pressure on cytoplasmic RNA viruses to maintain mechanisms that protect
      their messenger RNA from IFIT1 recognition. However, it is becoming increasingly
      clear that protein-protein interactions are necessary for optimal IFIT function.
      Recently, IFIT1, IFIT2 and IFIT3 have been shown to form a functional complex in
      which IFIT3 serves as a central scaffold to regulate and/or enhance the antiviral
      functions of the other two components. Moreover, IFITs interact with other
      cellular proteins to expand their contribution to regulation of the host
      antiviral response by modulating innate immune signalling and apoptosis. Here, we
      summarize recent advances in our understanding of the IFIT complex and review how
      this impacts on the greater role of IFIT proteins in the innate antiviral
      response.

PMID- 30234476
TI  - A polyphasic approach leads to seven new species of the cellulose-decomposing
      genus Sorangium, Sorangium ambruticinum sp. nov., Sorangium arenae sp. nov.,
      Sorangium bulgaricum sp. nov., Sorangium dawidii sp. nov., Sorangium kenyense sp.
      nov., Sorangium orientale sp. nov. and Sorangium reichenbachii sp. nov.
AB  - Seventy-three strains of Sorangium have been isolated from soil samples collected
      from all over the world. The strains were characterized using a polyphasic
      approach and phenotypic, genotypic and chemotype analyses clarified their
      taxonomic relationships. 16S rRNA, xynB1, groEL1, matrix-assisted laser
      desorption/ioniziation time-of-flight mass spectrometry and API-ZYM analyses were
      conducted. In addition, from selected representative strains, fatty acids,
      quinones and phospholipids were analysed. In silico DNA-DNA hybridization and DNA
      DNA hybridization against the current type species of Sorangiumcellulosum strain
      Soce 1871T (DSM 14627T) completed the analyses. Finally, our study revealed seven
      new species of Sorangium: Sorangium ambruticinum (Soce 176T; DSM 53252T, NCCB
      100639T, sequence accession number ERS2488998), Sorangium arenae (Soce 1078T; DSM
      105768T, NCCB 100643T, ERS2489002), Sorangium bulgaricum (Soce 321T; DSM 53339T,
      NCCB 100640T, ERS2488999), Sorangium dawidii (Soce 362T; DSM 105767T, NCCB
      100641T, ERS2489000), Sorangium kenyense (Soce 375T; DSM 105741T, NCCB 100642T,
      ERS2489001), Sorangium orientale (Soce GT47T; DSM 105742T, NCCB 100638T,
      ERS2501484) and Sorangium reichenbachii (Soce 1828T; DSM 105769T, NCCB 100644T,
      ERS2489003).

PMID- 30234478
TI  - Kyrpidia spormannii sp. nov., a thermophilic, hydrogen-oxidizing, facultative
      autotroph, isolated from hydrothermal systems at Sao Miguel Island, and emended
      description of the genus Kyrpidia.
AB  - A Gram-stain-positive, rod-shaped, non-motile, spore-forming bacterium, strain EA
      1T, was isolated from hydrothermal sediment samples from the Azores (Sao Miguel,
      Portugal). 16S rRNA gene sequence analysis of the isolated bacterium revealed a
      phylogenetic affiliation with the genus Kyrpidia. The sequence similarity of the
      five 16S rRNA gene copies to its closest relative, Kyrpidia tusciae, ranged from
      97.79 to 97.85 %. The in silico estimate of DNA-DNA hybridization was 56.0 %. The
      dominant fatty acids of the novel isolate were anteiso-C17 : 0 (49.9 %), iso-C17
      : 0 (23.0 %) and iso-C16 : 0 (13.3 %), while the quinone detected was menaquinone
      MK-7. Analysis of polar lipids identified phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylethanolamine and additional unidentified
      compounds comprising two glycolipids, two phospholipids and two lipids. The
      presence of meso-diaminopimelic acid in the peptidoglycan and mannose, arabinose
      and ribose in the cell wall of strain EA-1T were detected. The strain was able to
      grow heterotrophically as well as autotrophically with carbon dioxide as the sole
      carbon source and with hydrogen and oxygen as electron donor and acceptor,
      respectively. Based on its chemotaxonomic, physiological and genomic
      characteristics, the new strain is considered to represent a novel species within
      the genus Kyrpidia, for which the name Kyrpidiaspormannii sp. nov. is proposed.
      The type strain is strain EA-1T (=DSM 106492T=CCOS1194T).

PMID- 30234479
TI  - World Health Organization Early Warning, Alert and Response System in the
      Rohingya Crisis, Bangladesh, 2017-2018.
AB  - The Early Warning, Alert and Response System (EWARS) is a web-based system and
      mobile application for outbreak detection and response in emergency settings.
      EWARS provided timely information on epidemic-potential diseases among >700,000
      Rohingya refugees across settlements. EWARS helped in targeting new measles
      vaccination campaigns and investigating suspected outbreaks of acute jaundice
      syndrome.

PMID- 30234480
TI  - Standing frames for children with cerebral palsy: a mixed-methods feasibility
      study.
AB  - BACKGROUND: Standing frames are recommended as part of postural management for
      young people with cerebral palsy (CP) Gross Motor Function Classification System
      (GMFCS) level IV or V. They may have a variety of benefits, including improving
      bone mineral density, gastrointestinal function and social participation. The NHS
      needs to know if these benefits are real, given the cost implications of use and
      the reported negative effects (e.g. pain). The lack of evidence for the clinical
      effectiveness of standing frames demonstrates the need for evaluative research.
      OBJECTIVE(S): The aim of the study was to explore the acceptability of a future
      trial to determine the clinical effectiveness of standing frames. DESIGN: A
      sequential mixed-methods design was used. The findings of each stage informed the
      next stage. We conducted surveys, focus groups and in-depth interviews.
      PARTICIPANTS: Professionals who work with young people who use standing frames
      and parents who have a child who uses a standing frame took part in a survey of
      current standing frame practice (n = 551), a series of focus groups (seven focus
      groups, 49 participants in total) and a survey of research trial acceptability
      and feasibility (n = 585). Twelve young people who use a standing frame were
      interviewed. RESULTS: Standing frames were widely used as part of postural
      management for young people with CP both in school and at home but more
      frequently in school, and particularly by young people in primary school.
      Achieving the prescribed use was not always possible owing to resources,
      environment and family factors. Participation and activity engagement were
      important to young people. The majority of participants believed that standing
      frames research is necessary. Some reported concern that stopping standing frame
      use for a trial would cause irreversible damage. The maximum amount of time most
      health professionals and parents would agree to suspend standing frame use would
      be 12 weeks. LIMITATIONS: Owing to the nature of recruitment, we could not
      calculate response rates or determine non-response bias. Therefore, participants
      may not be representative of all standing frame users. CONCLUSIONS: Although
      parents and professionals who engaged in the qualitative aspect of this research
      and stakeholders who took part in the design workshops appreciated the lack of
      clinical evidence, our surveys, qualitative information and PPI demonstrated that
      most people had strong beliefs regarding the clinical effectiveness of standing
      frames. However, with key stakeholder engagement and careful planning, a trial
      would be acceptable. FUTURE WORK: We recommend a carefully planned trial that
      includes a pilot phase. The trial should evaluate the following question: 'does
      using a standing frame in school improve patient-reported outcomes of
      participation (primary outcome), quality of life, subjective well-being, body
      function and body structure (secondary outcomes) in young children (aged 4-11
      years) with CP GMFCS III-V?'. FUNDING: The National Institute for Health Research
      Health Technology Assessment programme.

PMID- 30234481
TI  - Morphological and molecular characterization of Onchocerca fasciata (Nematoda,
      Onchocercidae) from dromedary camels (Camelus dromedarius) in Iran.
AB  - Skin nodules of Onchocerca fasciata Railliet and Henry, 1910 (Spirurida,
      Onchocercidae) are a common finding in dromedary camels, though with a minimal
      clinical impact. There is little information about the morphology, molecular make
      up and pathological impact of this parasite. Onchocerca fasciata nodules (1.3-2.1
      cm in diameter and 509-841 mg in weight) were detected on the neck region in
      31.5% of dromedary camels examined in Kerman province, southeastern Iran. Of 38
      isolated nodules, only 23 (60.5%) contained viable worms. Measurement and
      morphological analyses were performed on isolated female worms by light
      microscopy. The identification of O. fasciata specimens was confirmed by sequence
      analysis of two mitochondrial genes (12S rDNA and cox1), which showed 0.4%
      divergence from available O. fasciata sequences. In addition, a phylogeny of
      filarial nematodes was constructed, based on these two mitochondrial genes and
      five nuclear genes (18S rDNA, 28S rDNA, MyoHC, rbp1, hsp70); this indicated that
      O. fasciata belongs to clade ONC3 of Onchocercidae, with representatives of the
      genera Onchocerca and Dirofilaria. Within the genus Onchocerca, O. fasciata is
      grouped with bovine parasitic species and the human parasitic Onchocerca
      volvulus, which suggests an impact of domestication on the radiation of the
      genus. Data provided here on the distribution and morphology of O. fasciata
      contribute to the molecular identification and phylogenetic position of the
      species.

PMID- 30234482
TI  - Three new species of Cucullanus (Nematoda: Cucullanidae) from marine fishes off
      New Caledonia, with a key to species of Cucullanus from Anguilliformes.
AB  - Based on light and scanning electron microscopical studies of nematode specimens
      from the digestive tract of some rarely collected anguilliform and perciform
      fishes off New Caledonia, three new species of Cucullanus Muller, 1777
      (Cucullanidae) are described: C. austropacificus n. sp. from the longfin African
      conger Conger cinereus (Congridae), C. gymnothoracis n. sp. from the lipspot
      moray Gymnothorax chilospilus (Muraenidae), and C. incognitus n. sp. from the
      seabream Dentex fourmanoiri (Sparidae). Cucullanus austropacificus n. sp. is
      characterized by the presence of cervical alae, ventral sucker, alate spicules
      1.30-1.65 mm long, conspicuous outgrowths of the anterior and posterior cloacal
      lips and by elongate-oval eggs measuring 89-108 * 48-57 MUm; C. gymnothoracis n.
      sp. is similar to the foregoing species, but differs from it in the absence of
      cervical alae and the posterior cloacal outgrowth, in the shape and size of the
      anterior cloacal outgrowth and somewhat shorter spicules 1.12 mm long; C.
      incognitus n. sp. (based on female morphology) differs from other congeneric
      species parasitic in the Sparidae mainly in possessing cervical alae, the
      postequatorial vulva, phasmids situated at the mid-length of the tail and in the
      size of the eggs (75-84 * 45-66 MUm). A key to species of Cucullanus parasitizing
      anguilliform fishes is provided.

PMID- 30234484
TI  - Barriers in Bangladesh.
AB  - Research laboratories in low- and middle-income countries, where the global
      burden of disease is highest, face systemic challenges in conducting research and
      public health surveillance. An international effort is needed to overcome the
      paywalls, customs regulations and lack of local suppliers that hinder the
      scientific community in these countries.

PMID- 30234485
TI  - Persistent coding of outcome-predictive cue features in the rat nucleus
      accumbens.
AB  - The nucleus accumbens (NAc) is important for learning from feedback, and for
      biasing and invigorating behaviour in response to cues that predict
      motivationally relevant outcomes. NAc encodes outcome-related cue features such
      as the magnitude and identity of reward. However, little is known about how
      features of cues themselves are encoded. We designed a decision making task where
      rats learned multiple sets of outcome-predictive cues, and recorded single-unit
      activity in the NAc during performance. We found that coding of cue identity and
      location occurred alongside coding of expected outcome. Furthermore, this coding
      persisted both during a delay period, after the rat made a decision and was
      waiting for an outcome, and after the outcome was revealed. Encoding of cue
      features in the NAc may enable contextual modulation of on-going behaviour, and
      provide an eligibility trace of outcome-predictive stimuli for updating stimulus
      outcome associations to inform future behaviour.

PMID- 30234483
TI  - Ezrin enrichment on curved membranes requires a specific conformation or
      interaction with a curvature-sensitive partner.
AB  - One challenge in cell biology is to decipher the biophysical mechanisms governing
      protein enrichment on curved membranes and the resulting membrane deformation.
      The ERM protein ezrin is abundant and associated with cellular membranes that are
      flat, positively or negatively curved. Using in vitro and cell biology
      approaches, we assess mechanisms of ezrin's enrichment on curved membranes. We
      evidence that wild-type ezrin (ezrinWT) and its phosphomimetic mutant T567D
      (ezrinTD) do not deform membranes but self-assemble anti-parallelly, zipping
      adjacent membranes. EzrinTD's specific conformation reduces intermolecular
      interactions, allows binding to actin filaments, which reduces membrane
      tethering, and promotes ezrin binding to positively-curved membranes. While
      neither ezrinTD nor ezrinWT senses negative curvature alone, we demonstrate that
      interacting with curvature-sensing I-BAR-domain proteins facilitates ezrin
      enrichment in negatively-curved membrane protrusions. Overall, our work
      demonstrates that ezrin can tether membranes, or be targeted to curved membranes,
      depending on conformations and interactions with actin and curvature-sensing
      binding partners.

PMID- 30234486
TI  - Quantification of gene expression patterns to reveal the origins of abnormal
      morphogenesis.
AB  - The earliest developmental origins of dysmorphologies are poorly understood in
      many congenital diseases. They often remain elusive because the first signs of
      genetic misregulation may initiate as subtle changes in gene expression, which
      are hard to detect and can be obscured later in development by secondary effects.
      Here, we develop a method to trace back the origins of phenotypic abnormalities
      by accurately quantifying the 3D spatial distribution of gene expression domains
      in developing organs. By applying Geometric Morphometrics to 3D gene expression
      data obtained by Optical Projection Tomography, we determined that our approach
      is sensitive enough to find regulatory abnormalities that have never been
      detected previously. We identified subtle but significant differences in the gene
      expression of a downstream target of a Fgfr2 mutation associated with Apert
      syndrome, demonstrating that these mouse models can further our understanding of
      limb defects in the human condition. Our method can be applied to different organ
      systems and models to investigate the etiology of malformations.

PMID- 30234489
TI  - EuroIntervention: at the crossroads of open access.

PMID- 30234490
TI  - Absence of proof or proof of absence? The risk of underpowered studies in
      cardiovascular medicine.

PMID- 30234491
TI  - Is the proximal left anterior descending coronary artery segment justifiably
      considered as the last frontier for stenting?

PMID- 30234487
TI  - UBE2G1 governs the destruction of cereblon neomorphic substrates.
AB  - The cereblon modulating agents (CMs) including lenalidomide, pomalidomide and CC
      220 repurpose the Cul4-RBX1-DDB1-CRBN (CRL4CRBN) E3 ubiquitin ligase complex to
      induce the degradation of specific neomorphic substrates via polyubiquitination
      in conjunction with E2 ubiquitin-conjugating enzymes, which have until now
      remained elusive. Here we show that the ubiquitin-conjugating enzymes UBE2G1 and
      UBE2D3 cooperatively promote the K48-linked polyubiquitination of CRL4CRBN
      neomorphic substrates via a sequential ubiquitination mechanism. Blockade of
      UBE2G1 diminishes the ubiquitination and degradation of neomorphic substrates,
      and consequent antitumor activities elicited by all tested CMs. For example,
      UBE2G1 inactivation significantly attenuated the degradation of myeloma survival
      factors IKZF1 and IKZF3 induced by lenalidomide and pomalidomide, hence
      conferring drug resistance. UBE2G1-deficient myeloma cells, however, remained
      sensitive to a more potent IKZF1/3 degrader CC-220. Collectively, it will be of
      fundamental interest to explore if loss of UBE2G1 activity is linked to clinical
      resistance to drugs that hijack the CRL4CRBN to eliminate disease-driving
      proteins.

PMID- 30234492
TI  - Polymer-free drug-coated stents: workhorse or "niche horse"?

PMID- 30234488
TI  - Learning recurrent dynamics in spiking networks.
AB  - Spiking activity of neurons engaged in learning and performing a task show
      complex spatiotemporal dynamics. While the output of recurrent network models can
      learn to perform various tasks, the possible range of recurrent dynamics that
      emerge after learning remains unknown. Here we show that modifying the recurrent
      connectivity with a recursive least squares algorithm provides sufficient
      flexibility for synaptic and spiking rate dynamics of spiking networks to produce
      a wide range of spatiotemporal activity. We apply the training method to learn
      arbitrary firing patterns, stabilize irregular spiking activity in a network of
      excitatory and inhibitory neurons respecting Dale's law, and reproduce the
      heterogeneous spiking rate patterns of cortical neurons engaged in motor planning
      and movement. We identify sufficient conditions for successful learning,
      characterize two types of learning errors, and assess the network capacity. Our
      findings show that synaptically-coupled recurrent spiking networks possess a vast
      computational capability that can support the diverse activity patterns in the
      brain.

PMID- 30234493
TI  - LAMPOON's European vacation.

PMID- 30234494
TI  - The ball is now in our court.

PMID- 30234495
TI  - Stenosis severity indices cannot reflect lumen loss in stent trials.

PMID- 30234496
TI  - Reply to the letter to the editor "Stenosis severity indices cannot reflect lumen
      loss in stent trials".

PMID- 30234497
TI  - Solution blow spinning (SBS)-assisted synthesis of well-defined carboxymethyl
      cellulose (CMC) nanowhiskers.
AB  - In this study, synthesis of well-defined carboxymethyl cellulose (CMC)
      nanowhiskers through a low-pressure solution blow spinning is achieved for the
      first time. A mixture of methanol, water, and CMC was sprayed through a locally
      available spray gun at 4 bars, and the collected sample was dried for two hours
      at 80  degrees C. Scanning electron microscopy and Fourier transform infrared
      spectroscopy characterized the samples. The results showed the successful
      production of many, uniform and well-defined nanowhiskers. The possible series of
      mechanisms is also discussed. The primary objective of this study is to give
      insights of a simple and straightforward method that has potential to mass
      produce high-quality nanowhiskers in a quick, cheap, and practical manner.

PMID- 30234498
TI  - Alternatives to patient specific verification measurements in proton therapy: a
      comparative experimental study with intentional errors.
AB  - Patient specific verification (PSV) measurements for pencil beam scanning (PBS)
      proton therapy are resource-consuming and necessitate substantial beam time
      outside of clinical hours. As such, efforts to safely reduce the PSV-bottleneck
      in the clinical work-flow are of great interest. Here, capabilities of current
      PSV methods to ensure the treatment integrity were investigated and compared to
      an alternative approach of reconstructing the dose distribution directly from the
      machine control- or delivery log files with the help of an independent dose
      calculation (IDC). Scenarios representing a wide range of delivery or work-flow
      failures were identified (e.g. error in spot position, air gap or pre-absorber
      setting) and machine files were altered accordingly. This yielded 21 corrupted
      treatment files, which were delivered and measured with our clinical PSV
      protocol. IDC machine- and log file checks were also conducted and their
      sensitivity at detecting the errors compared to the measurements. Although some
      of the failure scenarios induced clinically relevant dose deviations in the
      patient geometry, the PSV measurement protocol only detected one out of 21 error
      scenarios. However, 11 and all 21 error scenarios were detected using dose
      reconstructions based on the log and machine files respectively. Our data
      suggests that, although commonly used in particle therapy centers, PSV
      measurements do a poor job detecting data transfer failures and imperfect
      delivery machine performance. Machine- and log-file IDCs have been shown to
      successfully detect erroneous work-flows and to represent a reliable addition to
      the QA procedure, with the potential to replace PSV.

PMID- 30234500
TI  - Gastric-type Adenocarcinoma of the Cervix: Tumor With Wide Range of Histologic
      Appearances.
AB  - Gastric-type endocervical adenocarcinoma (GAS) is a recently described diagnostic
      entity originally characterized as a tumor with (1) voluminous cytoplasm that is
      (2) clear or pale eosinophilic, and (3) cells showing distinct cell borders.
      Since the initial tumor description there has been accumulating experience that
      the neoplasm, in addition to classic features, may show a wide spectrum of
      morphologic appearances. This paper describes and illustrates cases of GAS with
      focal or diffuse findings that include: densely eosinophilic cytoplasm, foamy
      cytoplasm, goblet cells, glands with elongated, stratified nuclei, glands with
      small cuboidal cells, glands with flattened cells, papillary growth, single cell
      infiltration and infiltration with microcystic elongated and fragmented pattern.
      All these patterns may bring up a differential diagnosis with other cervical
      malignancies such as usual, intestinal, endometrioid, clear cell, serous, and
      mesonephric adenocarcinoma. The paper describes the patterns of immunostaining of
      respective lesions that may aid in the diagnostic process and summarizes the main
      points of the differential diagnosis. GAS is associated with somatic and germline
      STK11 mutations and TP53 mutations but is invariably negative for human papilloma
      virus when tumor only is tested. It shows variation in incidence between
      countries. Awareness of the spectrum of morphologic appearances in GAS is
      important for accurate and confident diagnosis. Correct identification of GAS is
      important due to its propensity for ovarian and other distant metastases,
      markedly worse prognosis as compared with usual endocervical adenocarcinoma, and
      its relative resistance to chemotherapy.

PMID- 30234499
TI  - A multi-level memristor based on atomic layer deposition of iron oxide.
AB  - This work reports the fabrication of memristive devices based on iron oxide
      (Fe2O3) thin films grown by atomic layer deposition (ALD) using ferrocene as iron
      precursor and ozone as oxidant. An excellent control of the ALD process was
      achieved by using an experimental procedure based on a sequence of micro-pulses,
      which provided long residence time and homogeneous diffusion of precursors,
      allowing ALD of thin films with smooth morphology and crystallinity which was
      found to increase with layer thickness, at temperatures as low as 250  degrees C.
      The resistive switching of symmetric Pt/Fe2O3/Pt thin film devices exhibited
      bipolar mode with good stability and endurance. Multi-level switching was
      achieved via current and voltage control. It was proved that the ON state regime
      can be tuned by changing the current compliance while the OFF state can be
      changed to intermediate levels by decreasing the maximum voltage during RESET.
      The structural analysis of the switched oxide layer revealed the presence of nano
      sized crystalline domains corresponding to different iron oxide phases,
      suggesting that Joule heating effects during I-V cycling are responsible for a
      crystallization process of the pristine amorphous layer.

PMID- 30234501
TI  - An Update on the Role of Immunohistochemistry in the Evaluation of
      Gastrointestinal Tract Disorders.
AB  - As in other organ systems, immunohistochemistry (IHC) serves as an ancillary
      diagnostic tool for a wide variety of neoplastic and non-neoplastic disorders,
      including infections, work-up of inflammatory conditions, and subtyping neoplasms
      of the gastrointestinal (GI) tract. In addition, IHC is also used to detect a
      variety of prognostic and predictive molecular biomarkers for carcinomas of the
      GI tract. The purpose of this review is to highlight the use of IHC in common
      diagnostic scenarios throughout the tubular GI tract. The clinical indication and
      guidelines for performing IHC for detecting Helicobacter pylori is discussed
      along with role of gastrin and neuroendocrine markers in the diagnosis of
      autoimmune metaplastic atrophic gastritis. The major portion of this review
      discusses the use of IHC in the diagnostic workup of malignant neoplasms of the
      GI tract, such as adenocarcinoma versus squamous cell carcinoma, workup of poorly
      differentiated malignant neoplasms, and evaluation of uncommon gastric neoplasms
      (alpha-feto protein-producing carcinomas) and switch/sucrose-nonfermenting
      complex-deficient carcinomas. Lastly, localization of neuroendocrine tumors of
      unknown origin to aid clinical management, as well as HPV-driven anal neoplasia
      and IHC in the workup of basaloid anal neoplasms are also reviewed.

PMID- 30234502
TI  - Challenging the Requirement to Treat the Contralateral Neck in Cases With >4 mm
      Tumor Thickness in Patients Receiving Postoperative Radiation Therapy for
      Squamous Cell Carcinoma of the Oral Tongue or Floor of Mouth.
AB  - HYPOTHESIS: While treating patients with postoperative radiotherapy (RT) for
      squamous cell carcinoma of the oral tongue or floor of mouth, we hypothesized a
      low risk of tumor recurrence in the contralateral neck in the absence of
      contralateral neck RT when the primary tumor is >1 cm from the midline regardless
      of tumor thickness (TT) or depth of invasion (DOI)>4 mm. OBJECTIVE: The policy at
      our institution for many years has been to limit postoperative RT to the
      ipsilateral side when the primary tumor does not cross the midline, regardless of
      TT or DOI. We report the rate of isolated contralateral neck failure in this
      group. MATERIALS AND METHODS: We retrospectively reviewed all patients treated
      with postoperative RT at our institution between 1998 and 2014 for pathologic
      stage T1-T4 N1-N2b squamous cell carcinoma of the oral tongue or floor of mouth
      that did not cross the midline and thus were treated with RT limited to the
      primary site +/- ipsilateral neck. RESULTS: Our study population included 32
      patients: 75% with close (<5 mm) or positive margins and 38% with perineural
      invasion. No patients had a tumor that crossed the midline. TT was >=4 mm in 75%
      of patients. DOI was >5 mm in 68% of patients. There were no isolated
      contralateral neck recurrences with a median follow-up of 5 years. CONCLUSION:
      While delivering postoperative RT for oral tongue or floor of mouth cancer with
      pathologic neck stage N0-2b, the risk of not irradiating the contralateral neck
      is very low when the primary tumor does not cross the midline, regardless of
      other factors at the primary site, such as TT and DOI.

PMID- 30234503
TI  - Bloodstream Infections in Continuous Flow Left Ventricular Assist Device
      Recipients: Diagnostic and Clinical Implications.
AB  - Bloodstream infection (BSI) is a common complication of left ventricular assist
      device (LVAD) support and particularly difficult to treat. The presentation is
      often variable because of altered physiology and augmentation of cardiac output
      by the device. We studied LVAD recipients at a single institution. Multivariate
      logistic and Cox (with time-varying parameters) regression were implemented. Of
      212 patients, 58% experienced infections. Driveline infection (DLI) affected 31%,
      with 60% of them having deep-tissue involvement. Sixty-six patients (31%)
      suffered from 135 BSIs. Systemic inflammatory response syndrome (SIRS) was
      present in 47% of BSIs at presentation and associated with increased mortality.
      Right heart failure, destination therapy, INTERMACS, morbid obesity, and deep-DLI
      were independent risk factors for BSI. The BSI was independently associated with
      mortality. Bridge-to-transplantation (BTT) patients were more likely to receive
      transplant if they did not have BSIs. Among 104 BTT patients who received heart
      transplantation, development of BSI was associated with shorter time-to
      transplantation. Diagnosis of BSI poses diagnostic and prognostic challenges
      because of the hemodynamic profile of LVAD patients who may not mount the
      expected physiologic response to sepsis. Although SIRS criteria lack sensitivity
      in the LVAD population, SIRS signifies increased risk for death. Deep DLI was the
      strongest predictor of BSI. Despite the upgrade in listing status of BTT-LVADs
      with BSIs and shorter time-to-transplantation, BSI remain a major cause of
      mortality. BSIs are associated with significant mortality and should be regarded
      as a serious complication, similar to pump thrombosis and stroke.

PMID- 30234504
TI  - Conduction Abnormalities Associated with Tricuspid Annuloplasty in Cardiac
      Transplantation.
AB  - Prophylactic DeVega tricuspid annuloplasty (DVA) of the donor heart has been
      reported to improve tricuspid regurgitation (TR), renal dysfunction, and
      mortality in cardiac transplant recipients. This is the first study to
      investigate the electrical, as well as, hemodynamic effects of DVA during
      orthotopic heart transplantation (OHT). Electrocardiographic, echocardiographic,
      and hemodynamic data of 76 patients with DVA and 104 patients without DVA who
      underwent OHT between 2013 and 2017 at Columbia University Medical Center (New
      York, NY) were studied. Patients with DVA were older (56.5 +/- 1.2 vs. 52.4 +/-
      1.0 years of age; p = 0.017) and predominantly men (78% vs. 68%; p = 0.02). There
      were no significant differences in right ventricular function and TR. Patients
      with DVA had increased incidence of right bundle branch block compared with
      without DVA (37% +/- 5.9% vs. 9% +/- 2.9%; p < 0.001). Three patients with DVA
      developed complete heart block (CHB), whereas no patients without DVA developed
      CHB (p = 0.04). Four patients with DVA received a pacemaker (PPM), whereas only
      one patient in the without DVA group received a PPM. Complete heart block was
      significantly increased in patients who received prophylactic DVA. Possible risk
      of conduction abnormalities should be considered with performance of DVA
      annuloplasty in cardiac transplant recipients.

PMID- 30234505
TI  - Marked Practice Variation in Antithrombotic Care with the Berlin Heart EXCOR
      Pediatric Ventricular Assist Device.
AB  - Management of antithrombotic therapy (ATT) for pediatric ventricular assist
      devices is challenging, and the Berlin EXCOR remains the only FDA-approved
      option. Among those on the EXCOR, 28% have neurologic complications and major
      bleeding occurs in 50%. The Edmonton Protocol was developed to guide ATT, but the
      adverse event rate remains high, leading most centers to make modifications. The
      objective of this study is to characterize antithrombotic practice variation
      among North American pediatric ventricular assist device programs, in order to
      guide future research. In this descriptive cross-sectional study, a survey
      assessing antithrombotic (AT) practices was distributed by Berlin Heart Inc. to
      centers that implanted >=1 EXCOR between January 2012 and January 2016. Practices
      were compared at high- versus low-volume centers. High volume was defined as >=14
      implants in this period. Seventeen of 38 centers (44.7%) participated; 4 were
      high volume. At half of all centers (9/17), <=2 clinicians managed all AT
      decisions. Although 47.1% (8/17) followed the protocol "extremely/very closely,"
      only 5.9% (1/17) felt it to be "very effective." Most centers (10/15; 66.7%)
      deviated in >=2 protocol aspects. Over half modified either recommended
      antiplatelet agents (5/15) or anticoagulants (4/15). Adjunct medication use was
      highly variable. Most (11/17; 64.7%) deviated from protocol in either timing or
      type of AT lab monitoring. Despite widespread use of Thromboelastography
      (TEG)/Platelet Mapping (PM), concerns of inaccuracy were common. Most high-volume
      centers (3/4; 75%) abandoned TEG/PM as a primary tool. These practice variation
      analyses have identified areas in ATT that are amenable to care standardization
      and further research. Systematic study of optimal AT medication dosing and
      monitoring is needed.

PMID- 30234506
TI  - Quality Over Quantity: Standardization of Pediatric HeartWare Ventricular Assist
      Device Dressing Changes.
AB  - Pediatric patients are unique both in their diagnosis and clinical presentation
      before implantation of a ventricular assist device (VAD) and in their driveline
      site characteristics post-implant. There is limited evidence in scholarly
      literature that describes complications of pediatric VAD driveline sites or
      approaches by which to manage them. The Cardiac Center at The Children's Hospital
      of Philadelphia (CHOP) follows a standard of care for HeartWare VAD (HVAD)
      dressing changes in the inpatient setting with the goal of transitioning patients
      to weekly dressing changes by the time they are discharged to home. As a patient
      with an HVAD nears discharge, members of an interprofessional team collaborate
      with insurance providers and home care agencies to procure the appropriate
      supplies needed at home. Individualized plans of care are necessary for patients
      who are unable to transition to weekly dressings; however, customized products
      (such as silicone foam border dressings and antimicrobial agents) may be
      challenging to supply as single items from home care agencies. Between March 2014
      and June 2017, 15 patients underwent HVAD implantation, and eight (53%) were
      discharged home. Ten patients (67%) were able to transition to weekly dressing
      changes. Individualized plans of care for driveline site management were required
      for six (40%) patients with persistent drainage. Three patients (20%) experienced
      a driveline site infection. This article describes how a quality improvement (QI)
      initiative using rapid-cycle improvement methodology was executed to standardize
      HVAD dressing changes in our pediatric population.

PMID- 30234507
TI  - Conceptualizing Neonatal Abstinence Syndrome as a Cascade of Care: A Qualitative
      Study With Healthcare Providers in Ohio.
AB  - BACKGROUND: The opioid epidemic remains a serious issue in the United States and
      presents additional challenges for women of childbearing age. An increasingly
      common complication of opioid use is neonatal abstinence syndrome (NAS), or
      infant withdrawal from in utero exposure to opioids. PURPOSE: The objective of
      our qualitative study was to identify service needs and barriers to care in the
      NAS epidemic in Ohio, which has among the highest rates of opioid use and NAS in
      the nation. METHODS: Drawing on interviews with 18 healthcare providers, we
      investigated the challenges, opportunities, and service gaps in treating NAS.
      Open-ended questions covered opioid misuse and drug treatment, provision of and
      barriers to healthcare, and suggestions to improve prevention and programming.
      Content analysis identified major themes. FINDINGS: Providers were primarily
      women (67%) and included individuals working in healthcare administrative
      positions, hospital settings, clinics, and social support positions for pregnant
      women or new mothers. Our results suggest that rather than an acute diagnosis,
      NAS is better conceptualized as a "cascade of care" including (1) prevention, (2)
      prenatal care, including drug treatment, (3) labor and delivery, and (4)
      aftercare. Providers identified challenges and opportunities at each stage of the
      cascade that could influence NAS outcomes. IMPLICATIONS FOR PRACTICE: Our results
      suggest that greater resources, coordination, and cross-disciplinary education
      are urgently needed across the cascade of care to effectively address NAS.
      IMPLICATIONS FOR RESEARCH: Framing NAS as a cascade of care allows researchers to
      identify points along a cascade where mothers and infants require enhanced care
      and access to social and health services.

PMID- 30234508
TI  - Beyond the Quality Illusion: The Learning Era.
AB  - By highlighting the intangible, personal, contextual, and illusory nature of
      "quality," the authors reconceptualize quality improvement as a pluralistic and
      moral journey. They imagine a new era of quality improvement in which patients
      and health care providers work together to understand and achieve quality. The
      authors recommend, for the path forward, a "travel kit" of 10 crucial elements
      compassion, deliberation, flexible goals, ownership, the engagement of patients,
      the inclusion of payers, the involvement of learners, feedback loops, the
      fostering of learning, and the application of different sources of knowledge-to
      reframe quality improvement in a new era of learning.

PMID- 30234510
TI  - Right-to-Left Shunt During Transseptal Mitral Valve-in-Valve Replacement: A Case
      Report.
AB  - The following case report details an 88-year-old woman with severe mitral
      stenosis and moderate mitral regurgitation who presented with worsening dyspnea
      on exertion. The patient had undergone 4-vessel coronary artery bypass graft and
      mitral valve replacement 14 years before and was deemed high risk for redo
      sternotomy. A transseptal mitral valve-in-valve replacement was performed which
      resulted in intraoperative hypoxia and hypotension after atrial septal defect
      creation for valve deployment. A right-to-left shunt had developed due to the
      patient's underlying pulmonary hypertension. Successful atrial septal defect
      closure resolved the hypoxia and hypotension. The patient had a brief and
      uncomplicated postoperative course.

PMID- 30234509
TI  - All Other Things Being Equal: Exploring Racial and Gender Disparities in Medical
      School Honor Society Induction.
AB  - PURPOSE: A large body of literature has demonstrated racial and gender
      disparities in the physician workforce, but limited data are available regarding
      the potential origins of these disparities. To that end, the authors evaluated
      the effects of race and gender on Alpha Omega Alpha Honor Medical Society (AOA)
      and Gold Humanism Honor Society (GHHS) induction. METHOD: In this retrospective
      cohort study, the authors examined data from 11,781 Electronic Residency
      Application Service applications from 133 U.S. MD-granting medical schools to 12
      residency programs in the 2014-2015 application cycle and to all 15 residency
      programs in the 2015-2016 cycle at Yale-New Haven Hospital. They estimated the
      odds of induction into AOA and GHHS using logistic regression models, adjusting
      for Step 1 score, research publications, citizenship status, training
      interruptions, and year of application. They used gender- and race-matched
      samples to account for differences in clerkship grades and to test for bias.
      RESULTS: Women were more likely than men to be inducted into GHHS (odds ratio
      1.84, P < .001) but did not differ in their likelihood of being inducted into
      AOA. Black medical students were less likely to be inducted into AOA (odds ratio
      0.37, P < .05) but not into GHHS. CONCLUSIONS: These findings demonstrate
      significant differences between groups in AOA and GHHS induction. Given the
      importance of honor society induction in residency applications and beyond, these
      differences must be explored further.

PMID- 30234511
TI  - Implementation of Routine Cognitive Screening in the Preoperative Assessment
      Clinic.
AB  - Traditional systems of anesthesia evaluation do not routinely incorporate
      cognitive screening into preoperative assessments of vital organ systems.
      Increasing recognition of the importance of preoperative cognitive assessment of
      the elderly surgical patient has resulted in a "call to action" from experts in
      this area. A paradigm shift will be necessary to make this screening routine and
      not just a research tool. We describe our preliminary experience with developing
      a training program and implementing routine cognitive screening in a preoperative
      evaluation clinic. We outline a process showing our successful clinical
      implementation of sustainable cognitive stratification and documentation of
      routine cognitive screening.

PMID- 30234512
TI  - Anesthetic Management of a Pediatric Patient With Bardet-Biedl Syndrome.
AB  - Bardet-Biedl syndrome is a rare autosomal recessive genetic disorder that affects
      many organ systems. In cases of Bardet-Biedl syndrome, since the risk of
      developing inspiratory, cardiovascular, and metabolic problems is high,
      endotracheal intubation and anesthesia management are difficult. In this report,
      we present our experience in the management of anesthesia during endoscopic sinus
      surgery that was performed for the first time on a 6-year-old pediatric patient
      diagnosed with Bardet-Biedl syndrome.

PMID- 30234513
TI  - Ultrasound-Guided Percutaneous Cryoneurolysis for Postoperative Analgesia After
      Limb Amputation: A Case Series.
AB  - Pain after limb amputation is frequently challenging to adequately treat with
      local anesthetic-based regional anesthesia techniques due to its relatively long
      duration. Furthermore, uncontrolled pain in the immediate postoperative period is
      associated with persistent postsurgical pain, and frequently phantom limb pain.
      Cryoneurolysis is an alternative regional analgesic method to local anesthesia
      based techniques. We report 3 cases in which ultrasound-guided percutaneous
      cryoneurolysis was performed in the perioperative period of limb amputation. All
      reported profound analgesia in the postoperative period without persistent
      postsurgical residual limb or phantom pain in the following months. No adverse
      events associated with the cryoneurolysis procedure occurred.

PMID- 30234514
TI  - Thoracic Outlet Syndrome Treated With Injecting Botulinum Toxin Into Middle
      Scalene Muscle and Pectoral Muscle Interfascial Planes: A Case Report.
AB  - Thoracic outlet compression syndrome is a complex syndrome of neurovascular
      compression at the superior thoracic aperture, thought to occur at 1 of 3
      anatomical compartments: the interscalene triangle, the costoclavicular space,
      and the retropectoralis minor space. Injection into the middle interscalene
      muscle (ISM) and/or pectoralis muscle plane (PECS I and II) is gaining popularity
      because it provides significant symptomatic relief. A 44-year-old woman was
      diagnosed with thoracic outlet compression syndrome, with failed conservative
      therapy, including physical therapy. She refused surgical intervention. ISM and
      PECS I and II blocks with botulinum toxin type A were successful. In combination,
      PECS I/II and ISM injections can provide excellent symptomatic relief.

PMID- 30234515
TI  - Metabolic Acidosis in Postsurgical Patient on Canagliflozin and Metformin: A Case
      Report.
AB  - Canagliflozin is a novel drug for diabetes mellitus with the mechanisms of
      inducing glucosuria through inhibition of the sodium-glucose cotransporter 2 in
      the kidney independent of insulin activity. We are reporting euglycemic
      ketoacidosis with severe life-threatening metabolic acidosis. The 2 patients
      described had type 2 diabetes mellitus and were in a state of relative starvation
      after abdominal surgery. The first patient had been given an oral diet but was
      restricted with regard to calorie and sugar intake. The second patient had been
      nil per os since the operation.

PMID- 30234516
TI  - Using the SuperNO2VA Device on a Patient With a Known Difficult Airway: A Case
      Report Facilitating Fiberoptic Intubation and Postoperative Nasal Positive
      Pressure.
AB  - Upper airway obstruction during anesthesia is the leading cause of complications
      during sedation, intubation, and emergence. Devices to support oxygenation and
      ventilation are costly, require capital equipment, and cannot be used during
      transport. We present a 46-year-old man with sleep apnea and anticipated
      difficult airway undergoing a cardiac ablation under general endotracheal
      intubation. The SuperNO2VA nasal mask provided high-flow nasal oxygen and
      positive pressure during awake fiberoptic intubation and on extubation,
      maintaining airway patency in the operating room, during transport, and in
      recovery. The SuperNO2VA is inexpensive and portable and should be considered for
      high-risk patients with difficult airways.

PMID- 30234518
TI  - Physiatry Reviews for Evidence in Practice (PREP) Second Order Peer Reviews of
      Clinically Relevant Articles for the Physiatrist: Aspirin or Rivaroxaban for VTE
      Prophylaxis after Hip or Knee Arthroplasty.

PMID- 30234517
TI  - Addition of Infiltration Between the Popliteal Artery and the Capsule of the
      Posterior Knee and Adductor Canal Block to Periarticular Injection Enhances
      Postoperative Pain Control in Total Knee Arthroplasty: A Randomized Controlled
      Trial.
AB  - BACKGROUND: Periarticular injections (PAIs) are becoming a staple component of
      multimodal joint pathways. Motor-sparing peripheral nerve blocks, such as the
      infiltration between the popliteal artery and capsule of the posterior knee
      (IPACK) and the adductor canal block (ACB), may augment PAI in multimodal
      analgesic pathways for knee arthroplasty, but supporting literature remains rare.
      We hypothesized that the addition of ACB and IPACK to PAI would lower pain on
      ambulation on postoperative day (POD) 1 compared to PAI alone. METHODS: This
      triple-blinded randomized controlled trial included 86 patients undergoing
      unilateral total knee arthroplasty. Patients either received (1) a PAI (control
      group, n = 43) or (2) an IPACK with an ACB and modified PAI (intervention group,
      n = 43). The primary outcome was pain on ambulation on POD 1. Secondary outcomes
      included numeric rating scale (NRS) pain scores, patient satisfaction, and opioid
      consumption. RESULTS: The intervention group reported significantly lower NRS
      pain scores on ambulation than the control group on POD 1 (difference in means
      [95% confidence interval], -3.3 [-4.0 to -2.7]; P < .001). In addition, NRS pain
      scores on ambulation on POD 0 (-3.5 [-4.3 to -2.7]; P < .001) and POD 2 (-1.0 [
      1.9 to -0.1]; P = .033) were significantly lower. Patients in the intervention
      group were more satisfied, had less opioid consumption (P = .005, postanesthesia
      care unit, P = .028, POD 0), less intravenous opioids (P < .001), and reduced
      need for intravenous patient-controlled analgesia (P = .037). CONCLUSIONS: The
      addition of IPACK and ACB to PAI significantly improves analgesia and reduces
      opioid consumption after total knee arthroplasty compared to PAI alone. This
      study strongly supports IPACK and ACB use within a multimodal analgesic pathway.

PMID- 30234519
TI  - Evidence-Based Physiatry: Pediatric Neuromuscular Rehabilitation in the Era of
      Precision Medicine.

PMID- 30234520
TI  - Refined Criteria for Separating Low-grade Dysplasia and Nondysplastic Barrett
      Esophagus Reduce Equivocal Diagnoses and Improve Prediction of Patient Outcome: A
      10-Year Review.
AB  - The indefinite for dysplasia (IFD) category in Barrett esophagus (BE) is used for
      biopsies that are neither unequivocally dysplastic nor negative for dysplasia
      (NFD). In 2012, we refined our criteria so that BE with maintained cell polarity
      and surface gastric-type mucin vacuoles is considered NFD even with mild to
      moderate nuclear enlargement. A total of 1549 cases from 1130 patients with BE
      biopsies were identified from 2007 to 2016. Follow-up on patients with IFD
      biopsies was obtained to learn if the new thresholds better defined risk of
      progression. The earlier cases (2007-2011) were less likely than later cases
      (2012-2016) to be NFD (84.0% vs. 90.4%) and more likely to be IFD (8.4% vs.
      4.3%). The proportions of low-grade dysplasia (3.9% vs. 2.5%, high-grade
      dysplasia (1.4% vs. 1.3%), and intramucosal carcinoma (2.3% vs. 1.6%) were
      similar between the earlier and later cases, respectively. Later IFD cases were
      more frequently dysplastic (3/21, 14.3%) on the next biopsy than earlier cases
      (1/48, 2.1%). The rate of dysplasia on the next biopsy for NFD cases was not
      higher in the later cases (6/222, 2.7%) than the earlier cases (16/360, 4.4%).
      Improved diagnostic criteria reduced the proportion of IFD cases by nearly 50%
      from 2007 to 2016. This change coincided with a higher proportion of IFD cases
      having dysplasia on the next biopsy. NFD patients had no increase in dysplasia on
      the next biopsy providing evidence that dysplastic cases are not missed by the
      refined criteria.

PMID- 30234521
TI  - Influences of COMT rs4680 and OPRM1 rs1799971 Polymorphisms on Chronic
      Postsurgical Pain, Acute Pain, and Analgesic Consumption After Elective Cesarean
      Delivery.
AB  - OBJECTIVES: The main objectives of this study were to assess the effects of
      cathechol-O-methyl-transferase (COMT) rs4680 and MU-opioid receptor rs1799971
      polymorphisms alone or genotype combinations on chronic postsurgical pain (CPSP),
      acute pain, and analgesic consumption after elective cesarean delivery in a
      Chinese cohort. MATERIALS AND METHODS: Two hundred sixty-six patients undergoing
      elective cesarean delivery with a Pfannenstiel incision under spinal anesthesia
      were enrolled in this prospective, observational study. All patients were
      screened for rs4680 and rs1799971 using a peripheral venous blood sample of DNA.
      Postoperative pain relief was provided by IV patient-controlled analgesia with
      sufentanyl and tramadol for 48 hours postoperatively. Postoperative pain scores
      and analgesic consumption were assessed, and CPSP was evaluated 3 months after
      surgery in all patients. RESULTS: Twenty-nine patients (29/266; 10.9%) developed
      CPSP at 3 months after surgery. The risk factors for CPSP included previous
      cesarean delivery and higher analgesic consumptions at 24 hours and 48 hours
      postoperatively (P=0.032, 0.015, and 0.008, reapectively). No associations were
      found between CPSP and a single rs4680 and rs1799971 polymorphism, or their
      combinations (P>0.05). In contrast, patients with rs1799971 GG required higher
      patient-controlled analgesics at 24 hours and 48 hours postoperatively compared
      with those with other genotypes (GG>AG>AA). However, no significant effects of
      interactions between the 2 single nucleotide polymorphisms on analgesic
      consumption were observed. DISCUSSION: Our results indicate that cathechol-O
      methyl-transferase rs4860 and MU-opioid receptor rs1799971 may not contribute to
      CPSP development after cesarean delivery. The genotype of rs1799971 affects
      postcesarean analgesic requirement, while the rs4680 do not. Additional larger
      studies are needed to confirm these findings.

PMID- 30234522
TI  - Effects of Polyethylene Glycol-20k on Postresuscitation Myocardial and Cerebral
      Function in a Rat Model of Cardiopulmonary Resuscitation.
AB  - OBJECTIVES: Polyethylene glycol-20k is a hybrid cell impermeant that reduces
      ischemia injury and improves microcirculatory flow during and following low flow
      states through nonenergy-dependent water transfer in the microcirculation. We
      investigated the effects of polyethylene glycol-20k on postresuscitation
      microcirculation, myocardial and cerebral function, and duration of survival in a
      rat model of cardiopulmonary resuscitation. DESIGN: Ventricular fibrillation was
      induced in 20 male Sprague Dawley rats and untreated for 6 minutes. Animals were
      randomized into two groups (n = 10 for each group): polyethylene glycol-20k and
      control. Polyethylene glycol-20k (10% solution in saline, 10% estimated blood
      volume) and vehicle (saline) were administered at the beginning of
      cardiopulmonary resuscitation by continuous IV infusion. Resuscitation was
      attempted after 8 minutes of cardiopulmonary resuscitation. SETTING: University
      Affiliated Research Laboratory. SUBJECTS: Sprague Dawley Rats. INTERVENTIONS:
      Polyethylene glycol-20k. MEASUREMENTS AND MAIN RESULTS: Buccal microcirculation
      was measured at baseline, 1, 3, and 6 hours after return of spontaneous
      circulation using a side-stream dark-field imaging device. Myocardial function
      was measured by echocardiography at baseline and every hour postresuscitation for
      6 hours. The animals were then returned to their cage and observed for an
      additional 72 hours. Neurologic Deficit Scores were recorded at 24, 48, and 72
      hours after resuscitation. Postresuscitation ejection fraction, cardiac output,
      and myocardial performance index were significantly improved in animals treated
      with polyethylene glycol-20k (p < 0.05). Perfused buccal vessel density and
      microcirculatory flow index values were significantly higher at all time points
      in the polyethylene glycol-20k group compared with the control group.
      Postresuscitation cerebral function and survival rate were also significantly
      improved in animals that received polyethylene glycol-20k. CONCLUSIONS:
      Administration of polyethylene glycol-20k following cardiopulmonary resuscitation
      improves postresuscitation myocardial and cerebral function, buccal
      microcirculation, and survival in a rat model of cardiopulmonary resuscitation.

PMID- 30234523
TI  - Outcomes of Older Hospitalized Patients Requiring Rapid Response Team Activation
      for Acute Deterioration.
AB  - OBJECTIVES: Rapid response teams are groups of healthcare providers that have
      been implemented by many hospitals to respond to acutely deteriorating patients
      admitted to the hospital wards. Hospitalized older patients are at particular
      risk of deterioration. We sought to examine outcomes of older patients requiring
      rapid response team activation. DESIGN: Analysis of a prospectively collected
      registry. SETTING: Two hospitals within a single tertiary care level hospital
      system between 2012 and 2016. PATIENTS: Five-thousand nine-hundred ninety-five
      patients were analyzed. Comparisons were made between older patients (defined as
      >= 75 yr old) and younger patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: All patient information, outcomes, and rapid response team activation
      information were gathered at the time of rapid response team activation and
      assessment. The primary outcome was in-hospital mortality, analyzed using
      multivariate logistic regression. Two-thousand three-hundred nine were older
      patients (38.5%). Of these, 835 (36.2%) died in-hospital, compared with 998
      younger patients (27.1%) (adjusted odds ratio, 1.83 [1.54-2.18]; p < 0.001).
      Among patients admitted from home, surviving older patients were more likely to
      be discharged to a long-term care facility (adjusted odds ratio, 2.38 [95% CI,
      1.89-3.33]; p < 0.001). Older patients were more likely to have prolonged delay
      to rapid response team activation (adjusted odds ratio, 1.79 [1.59-2.94]; p <
      0.001). Among patients with goals of care allowing for ICU admission, older
      patients were less likely to be admitted to the ICU (adjusted odds ratio, 0.66
      [0.36-0.79]), and less likely to have rapid response team activation during
      daytime hours (adjusted odds ratio, 0.73 [0.62-0.98]; p < 0.001). CONCLUSIONS:
      Older patients with in-hospital deterioration requiring rapid response team
      activation had increased odds of death and long-term care disposition. Rapid
      response team activation for older patients was more likely to be delayed, and
      occur during nighttime hours. These findings highlight the worse outcomes seen
      among older patients with in-hospital deterioration, identifying areas for future
      quality improvement.

PMID- 30234524
TI  - Internet eating disorder prevention.
AB  - PURPOSE OF REVIEW: Internet prevention of eating disorders is a relatively new
      field that is expanding rapidly. We review randomized controlled trial designs
      examining the efficacy of Internet prevention in eating disorders that have
      emerged from 2016. RECENT FINDINGS: Our literature search identified five studies
      that used randomized controlled trial designs to examine the efficacy of Internet
      prevention in eating disorders. All of the studies represented indicated
      prevention, that is, young women who have body image concerns. Three specific
      approaches were examined: media literacy, cognitive dissonance, and cognitive
      behavior therapy. All studies indicated significantly more impact of the
      intervention than a control condition, with between group effect sizes at follow
      up ranging from 0.24 to 0.42. SUMMARY: Although Internet interventions for eating
      disorders may be less effective than face-to-face interventions, and attrition
      increases when populations are used that reflect real-world usage, these
      interventions have an important role in a stepped-care approach. Future research
      should make direct comparisons of different Internet programs with a view to
      helping us understand who will gain most benefit out of which approach, including
      who requires moderated Internet approaches and who does not.

PMID- 30234525
TI  - Diagnosis and classification of personality disorders: novel approaches.
AB  - PURPOSE OF REVIEW: To provide an update of the recent studies, which have
      evaluated the radical changes in personality disorder classification in DSM-5 and
      ICD-11. RECENT FINDINGS: Although the DSM-5 Committee rejected the personality
      disorders Work Group proposal for personality disorder classification, the model
      was published in DSM-5 Section III. This Alternative Model of Personality
      Disorders (AMPD) has been widely adopted by the research community resulting in
      multiple studies evaluating its reliability and clinical utility. The ICD-11
      Personality Classification has recently been accepted by the WHO and is also
      receiving increasing study. Both models emphasize personality disorder severity,
      which most studies report is consistently linked to impairment and outcome. Both
      models propose five descriptive domains, which appear to capture most of the
      current personality disorder diagnoses, and can also be linked to disease
      extremes of normal personality such as the Five Factor Model. SUMMARY: The
      changes in DSM-5 AMPD and ICD-11 represent a significant paradigm shift in the
      diagnosis of personality disorders. Early research suggests that the changes may
      be beneficial for clinicians and researchers. The models more closely align with
      the large body of literature supporting dimensional models of normal personality.
      The severity dimensions are consistent with the large body of evidence that
      personality disorder severity is a strong determinant of impairment and outcome.
      It remains to be seen if clinicians will use the classification to plan and
      predict treatment for a wide range of mental disorders.

PMID- 30234526
TI  - Current conceptualizations of narcissism.
AB  - PURPOSE OF REVIEW: Definitions of narcissism have traditionally differed across
      psychiatry and subfields of psychology. This review aims to highlight emerging
      points of consensus and suggest further directions needed to obtain a more
      comprehensive and cohesive conceptualization of the construct. RECENT FINDINGS:
      An emerging consensus is that stable individual differences in the phenotypic
      expression of narcissism are best captured with a taxonomy that includes the core
      traits of entitlement, grandiosity, and vulnerability. Recent work has also begun
      to conceptualize and assess narcissistic states matched with these dimensions. We
      combine emerging taxonomic knowledge with principles from Whole Trait Theory to
      propose a multilevel conceptualization of narcissism that focuses on its
      manifestation at the trait level, state level, and within-situation level.
      SUMMARY: Efforts to understand the phenotypic structure of the core traits
      associated with narcissism have been successful. As the field moves forward, it
      will become critical for researchers studying narcissism at multiple levels to
      align and integrate these perspectives so that a more comprehensive and cohesive
      conceptualization of the construct can be developed.

PMID- 30234527
TI  - Pneumoperitoneum after Cardiopulmonary Resuscitation.

PMID- 30234528
TI  - Ultrasound-Assisted Technology Versus the Conventional Landmark Location Method
      in Spinal Anesthesia for Cesarean Delivery in Obese Parturients: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Spinal anesthesia, which is commonly used in cesarean deliveries, is
      often difficult to perform in obese parturients because of poorly palpable
      surface landmarks and positioning challenges. This study aimed to evaluate the
      benefits of ultrasound-assisted technology for performing spinal anesthesia in
      obese parturients. METHODS: Parturients with a body mass index (BMI) >=30 kg/m
      scheduled for elective cesarean delivery were randomized to undergo spinal
      anesthesia using the conventional landmark location technique (landmark group, n
      = 40) or prepuncture ultrasound examination (ultrasound group, n = 40). All
      participants underwent spinal anesthesia in the lateral position. The primary
      outcome was the first-attempt success rate. Secondary outcomes were the number of
      skin punctures and needle passes, procedure times, patient satisfaction, changes
      in the intended interspace, and incidence of complications. RESULTS: The
      ultrasound group had a significantly higher first-attempt success rate (87.5% vs
      52.5%; P = .001), fewer cases requiring >10 needle passes (1 vs 17; P < .001),
      and fewer skin punctures and needle passes (P < .001 for both). There was no
      statistically significant difference in the time taken to identify the needle
      insertion site between the 2 groups (202.5 vs 272.0 seconds; P = .580). Both the
      spinal injection time and total procedure time were significantly longer in the
      landmark group (P < .001). Patient satisfaction scores were significantly higher
      in the ultrasound group (P = .001). Among patients with BMI between 30 and 34.9
      kg/m, there was no statistically significant difference in the first-attempt
      success rate (P = .407), number of cases with >10 needle passes (P = .231),
      spinal injection time (P = .081), or total procedure time (P = .729); however,
      more time was required to identify the needle insertion site in the ultrasound
      group (P < .001). For patients with BMI between 35 and 43 kg/m, the ultrasound
      group had a significantly higher first-attempt success rate (P <= .041), fewer
      cases with >10 needle passes (P <= .01), and shorter procedure times, including
      the time required to identify the needle insertion site (P < .001). CONCLUSIONS:
      Prepuncture ultrasound examination can facilitate spinal anesthesia in the
      lateral position in obese parturients (35 kg/m <= BMI <= 43 kg/m) by improving
      the first-attempt success rate, reducing the number of needle passes and puncture
      attempts, shortening the total procedure time, and improving patient
      satisfaction.

PMID- 30234529
TI  - Predatory Open-Access Publishing in Anesthesiology.
AB  - Predatory publishing is an exploitative fraudulent open-access publishing model
      that applies charges under the pretense of legitimate publishing operations
      without actually providing the editorial services associated with legitimate
      journals. The aim of this study was to analyze this phenomenon in the field of
      anesthesiology and related specialties (intensive care, critical and respiratory
      medicine, pain medicine, and emergency care). Two authors independently surveyed
      a freely accessible, constantly updated version of the original Beall lists of
      potential, possible, or probable predatory publishers and standalone journals. We
      identified 212 journals from 83 publishers, and the total number of published
      articles was 12,871. The reported location of most publishers was in the United
      States. In 43% of cases (37/84), the reported location was judged as "unreliable"
      after being checked using the 3-dimensional view in Google Maps. Six journals
      were indexed in PubMed. Although 6 journals were declared to be indexed in the
      Directory of Open Access Journals, none were actually registered. The median
      article processing charge was 634.5 US dollars (interquartile range, 275-1005 US
      dollars). Several journals reported false indexing/registration in the Committee
      on Publication Ethics and International Committee of Medical Journal Editors
      registries and Google Scholar. Only 32% (67/212) reported the name of the editor
      in-chief. Rules for ethics/scientific misconduct were reported in only 24% of
      cases (50/212). In conclusion, potential or probable predatory open-access
      publishers and journals are widely present in the broad field of anesthesiology
      and related specialties. Researchers should carefully check journals' reported
      information, including location, editorial board, indexing, and rules for ethics
      when submitting their manuscripts to open-access journals.

PMID- 30234530
TI  - Society for Perioperative Assessment and Quality Improvement Reply to "American
      Society of Enhanced Recovery: Advancing Enhanced Recovery and Perioperative
      Medicine".

PMID- 30234531
TI  - In Response.

PMID- 30234532
TI  - In Response.

PMID- 30234533
TI  - A Predictive Model for Determining Patients Not Requiring Prolonged Hospital
      Length of Stay After Elective Primary Total Hip Arthroplasty.
AB  - BACKGROUND: Hospital length of stay (LOS) is an important quality metric for
      total hip arthroplasty. Accurately predicting LOS is important to expectantly
      manage bed utilization and other hospital resources. We aimed to develop a
      predictive model for determining patients who do not require prolonged LOS.
      METHODS: This was a retrospective single-institution study analyzing patients
      undergoing elective unilateral primary total hip arthroplasty from 2014 to 2016.
      The primary outcome of interest was LOS less than or equal to the expected
      duration, defined as <=3 days. Multivariable logistic regression was performed to
      generate a model for this outcome, and a point-based calculator was designed. The
      model was built on a training set, and performance was assessed on a validation
      set. The area under the receiver operating characteristic curve and the Hosmer
      Lemeshow test were calculated to determine discriminatory ability and goodness-of
      fit, respectively. Predictive models using other machine learning techniques
      (ridge regression, Lasso, and random forest) were created, and model performances
      were compared. RESULTS: The point-based score calculator included 9 variables:
      age, opioid use, metabolic equivalents score, sex, anemia, chronic obstructive
      pulmonary disease, hypertension, obesity, and primary anesthesia type. The area
      under the receiver operating characteristic curve of the calculator on the
      validation set was 0.735 (95% confidence interval, 0.675-0.787) and demonstrated
      adequate goodness-of-fit (Hosmer-Lemeshow test, P = .37). When using a score of
      12 as a threshold for predicting outcome, the positive predictive value was
      86.1%. CONCLUSIONS: A predictive model that can help identify patients at higher
      odds for not requiring a prolonged hospital LOS was developed and may aid
      hospital administrators in strategically planning bed availability to reduce both
      overcrowding and underutilization when coordinating with surgical volume.

PMID- 30234534
TI  - Development and Multidisciplinary Preliminary Validation of a 3-Dimensional
      Printed Pediatric Airway Model for Emergency Airway Front-of-Neck Access
      Procedures.
AB  - BACKGROUND: Pediatric-specific difficult airway guidelines include algorithms for
      3 scenarios: unanticipated difficult tracheal intubation, difficult mask
      ventilation, and cannot intubate/cannot ventilate. While rare, these instances
      may require front-of-neck access (FONA) to secure an airway until a definitive
      airway can be established. The aim of this study was to develop a pediatric FONA
      simulator evaluated by both anesthesiology and otolaryngology providers,
      promoting multidisciplinary airway management. METHODS: A 3-dimensional-printed
      tracheal model was developed using rescaled, anatomically accurate dimensions
      from a computerized tomography scan using computer-aided design software. The
      medical grade silicone model was incorporated into a mannequin to create a low
      cost, high-fidelity simulator. A multidisciplinary team of anesthesiology,
      otolaryngology, and simulation experts refined the model. Experts in airway
      management were recruited to rate the realism of the model's characteristics and
      features and their own ability to complete specific FONA-related tasks. RESULTS:
      Six expert raters (3 anesthesiology and 3 otolaryngology) were identified for
      multidisciplinary evaluation of model test content validity. Analysis of response
      data shows null variance within 1 or both specialties for a majority of the
      content validity tool elements. High and consistent absolute ratings for each
      domain indicate that the tested experts perceived this trainer as a realistic and
      highly valuable tool in its current state. CONCLUSIONS: The ability to practice
      front-of-neck emergency airway procedures safely and subsequently demonstrate
      proficiency on a child model has great implications regarding both quality of
      physician training and patient outcomes. This model may be incorporated into
      curricula to teach needle cricothyroidotomy and other FONA procedures to
      providers across disciplines.

PMID- 30234535
TI  - Of Flies and Men.

PMID- 30234536
TI  - HES or How to End Science.

PMID- 30234537
TI  - Retrospective Cohort Study on the Optimal Timing of Orogastric Tube/Nasogastric
      Tube Insertion in Infants With Pyloric Stenosis.
AB  - BACKGROUND: Hypertrophic pyloric stenosis in infants can cause a buildup of
      gastric contents. Orogastric tubes (OGTs) or nasogastric tubes (NGTs) are often
      placed in patients with pyloric stenosis before surgical management to prevent
      aspiration. However, exacerbation of gastric losses may lead to electrolyte
      abnormalities that can delay surgery, and placement has been associated with
      increased risk of postoperative emesis. Currently, there are no evidence-based
      guidelines regarding OGT/NGT placement in these patients. This study examines
      whether OGT/NGT placement before arrival in the operating room was associated
      with a longer time to readiness for surgery as defined by normalization of
      electrolytes. Secondary outcomes included time from surgery to discharge and
      ability to tolerate feeds by 6 hours postoperatively in patients with and without
      early OGT/NGT placement. METHODS: In this multicenter retrospective cohort study,
      data were extracted from the medical records of 481 patients who underwent
      pyloromyotomy for infantile hypertrophic pyloric stenosis from March 2013 to June
      2016. Multivariable linear regression and Cox proportional hazard models were
      constructed to evaluate the association between placement of an OGT/NGT at the
      time of admission with increased time to readiness for surgery (defined as the
      time from admission to the first set of normalized laboratory values) and
      increased time from surgery to discharge. Multivariable logistic regression was
      used to evaluate the association between early OGT/NGT placement and the ability
      to tolerate oral intake at 6 hours postsurgery. Analyses were adjusted for site
      differences. RESULTS: Among patients admitted with electrolyte abnormalities,
      those with an OGT/NGT placed on presentation required more time until their serum
      electrolytes were at acceptable levels for surgery by regression analysis (19.2
      hours difference; 95% confidence interval, 10.05-28.41; P < .001), after
      adjusting for site. Overall, patients who had OGTs/NGTs placed before
      presentation in the operating room had a longer length of stay from surgery to
      discharge than those without (38.8 hours difference; 95% confidence interval,
      25.35-52.31; P < .001), after adjusting for site. OGT/NGT placement before
      surgery was not associated with failure to tolerate oral intake within 6 hours of
      surgery after adjusting for site, corrected gestational age, and baseline serum
      electrolytes. CONCLUSIONS: OGT/NGT placement on admission for pyloric stenosis is
      associated with a longer time to electrolyte correction in infants with abnormal
      laboratory values on presentation and, subsequently, a longer time until they are
      ready for surgery. It is also associated with longer postoperative hospital stay
      but not an increased risk of feeding intolerance within 6 hours of surgical
      repair.

PMID- 30234538
TI  - Ventilator Alarms in Intensive Care Units: Frequency, Duration, Priority, and
      Relationship to Ventilator Parameters.
AB  - Ventilator alarms have long been presumed to contribute substantially to the
      overall alarm burden in the intensive care unit. In a prospective observational
      study, we determined that each ventilator triggered an alarm cascade of up to 8
      separate notifications once every 6 minutes. In 1 intensive care unit with
      different ventilator manufacturers, the distribution of high-priority alarms was
      manufacturer dependent with 8.6% of alarms from 1 type and 89.8% of alarms from
      another type of ventilator. Alarm limits were not a function of patient-specific
      ventilator settings.

PMID- 30234539
TI  - Comparison of 7 Different Sensors for Detecting Low Respiratory Rates Using a
      Single Breath Detection Algorithm in Nonintubated, Sedated Volunteers.
AB  - BACKGROUND: Numerous technologies are used to monitor respiratory rates in
      nonintubated patients. No technology has emerged as the standard. The primary aim
      of this study was to assess the limits of agreement between a reference sensor
      signal (respiratory inductance plethysmography bands) and 7 alternative sensor
      signals (nasal capnometer, nasal pressure transducer, oronasal thermistor,
      abdominal accelerometer, transpulmonary electrical impedance, peritracheal
      microphone, and photoplethysmography) for measuring low respiratory rates in
      sedated, nonintubated, supine volunteers. A unified approach based on a single
      breath detection algorithm was applied to each sensor to facilitate comparison.
      We hypothesized that all of the sensor signals would allow detection of low (<10
      breaths per minute) respiratory rates to within +/-2 breaths per minute of the
      reference sensor signal. METHODS: Volunteers received remifentanil and propofol
      infusions at selected target concentration pairs to induce depression of
      ventilation. Signals from each sensor were analyzed by an identical threshold
      based detection algorithm to compute the breathing rate. Bland-Altman limits of
      agreement and error rate analyses were used to characterize the performance of
      each sensor compared to the reference sensor. RESULTS: The analysis of the
      accelerometer and capnometer signals, using Bland-Altman and error rate analyses,
      showed the highest breath rate agreement (1.96 * standard deviation) of the 7
      sensors with -2.1 to 2.2 and -2.5 to 2.7 breaths per minute, respectively. All
      other signals exhibited wider limits of agreement, with impedance being the
      widest at -7.8 to 7.4 breaths per minute. For the abdomen accelerometer, 95% of
      Bland-Altman data points were within +/-2 breaths per minute. For the capnometer,
      96% of data points were within +/-2 breaths per minute. Nasal pressure,
      thermistor, and microphone all had >80% of data points within +/-2 breaths per
      minute. Impedance and photoplethysmograph signals had 58% and 64%, respectively.
      CONCLUSIONS: A unified approach can be applied to a variety of sensor signals to
      estimate respiratory rates in spontaneously breathing, nonintubated, sedated
      volunteers. However, detecting clinically relevant low respiratory rates (<6
      breaths per minute) is a technical challenge. By our analysis, no single sensor
      was able to detect slow respiratory rates with adequate precision (<+/-2 breaths
      per minute of the reference signal). Of the sensors evaluated, capnometers and
      abdominal accelerometers may be the most reliable sensors for identifying
      hypopnea and central apnea.

PMID- 30234540
TI  - Too Early to Jump Ship on Whole Blood for Hemorrhagic Trauma?

PMID- 30234541
TI  - In Response.

PMID- 30234542
TI  - Effects of Intraoperative Infusion of Esmolol on Systemic and Pulmonary
      Inflammation in a Porcine Experimental Model of Lung Resection Surgery.
AB  - BACKGROUND: Lung resection surgery (LRS) is associated with systemic and
      pulmonary inflammation, which can affect postoperative outcomes. Activation of
      beta-adrenergic receptors increases the expression of proinflammatory and anti
      inflammatory mediators, and their blockade may attenuate the systemic
      inflammatory response. The aim of this study was to analyze the effect of a
      continuous perioperative intravenous perfusion of esmolol on postoperative
      pulmonary edema in an experimental model of LRS requiring periods of one-lung
      ventilation (OLV). METHODS: Twenty-four large white pigs were randomly assigned
      to 3 groups: control (CON), esmolol (ESM), and sham. The ESM group received an
      intravenous esmolol bolus (0.5 mg/kg) and then an esmolol infusion (0.05
      mg.kg.minute) throughout the procedure. The CON group received the same volume of
      0.9% saline solution as the ESM group plus a continual infusion of saline. The
      sham group underwent a left thoracotomy without LRS or OLV. At the end of the
      LRS, the animals were awakened, and after 24 hours, they underwent general
      anesthesia again. Lung biopsies and plasma samples were obtained to analyze the
      levels and expression of inflammatory mediators, and the animals also received a
      bronchoalveolar lavage. RESULTS: At 24 hours after the operation, the ESM group
      had less lung edema and lower expression of the proinflammatory biomarkers tumor
      necrosis factor (TNF) and interleukin (IL)-1 compared to the CON group for both
      lung lobes. For the mediastinal lobe biopsies, the mean difference and 95%
      confidence interval (CI) between the groups for edema, TNF, and IL-1 were 14.3
      (95% CI, 5.6-23.1), P = .002; 0.19 (95% CI, 0.07-0.32), P = .002; and 0.13 (95%
      CI, 0.04-0.22), P = .006, respectively. In the left upper lobe, the mean
      differences for edema, TNF, and IL-1 were 12.4 (95% CI, 4.2-20.6), P = .003; 0.25
      (95% CI, 0.12-0.37), P < .001; and 0.3 (95% CI, 0.08-0.53), P = .009.
      CONCLUSIONS: Our results suggest that esmolol reduces lung edema and inflammatory
      responses in the intraoperative and postoperative periods in animals that
      underwent LRS with OLV.

PMID- 30234543
TI  - Thromboelastography in the management of snakebite-induced coagulopathy: a case
      series and literature review.
AB  - : North American crotaline envenomations are a significant source of morbidity
      annually. Envenomation is marked by a constellation of effects that can include
      severe tissue damage, systemic effects such as anaphylaxis, and coagulopathy with
      bleeding. Traditionally, static plasma-derived tests such as protime and PTT are
      used to assess coagulation status. However, other tests are available that
      provide a whole blood assessment of all portions of coagulation including
      initiation, propagation, and clot maintenance. One such analytical test is TEG.
      Minimal data is available regarding the effect of snake venom on TEG results. We
      report on three cases of North American crotaline envenomation with subsequent
      TEG analysis. Our results show that TEG analysis does relate the same information
      as traditional monitoring parameters. Although only in an isolated case, the TEG
      analysis potentially revealed a fibrinolytic process prior to the same process
      being apparent with traditional monitoring. Future research is necessary to
      identify the role of TEG in crotaline snakebite management.

PMID- 30234545
TI  - Thrombogenesis and thrombotic disorders based on 'two-path unifying theory of
      hemostasis': philosophical, physiological, and phenotypical interpretation.
AB  - : Hemostasis, endowed to human to protect lives, is a process of logical blood
      clotting system to prevent blood loss in vascular injury. However, the notion
      that deadly thrombosis occurs as a result of normal hemostasis in intravascular
      injury could encounter with conceptual skepticism because the term 'thrombosis'
      automatically conjures up as serious disease. According to 'two-path unifying
      theory', normal hemostasis is initiated only by vascular injury through activated
      unusually large von Willebrand factor (ULVWF) path and/or activated tissue factor
      (TF) path. When these two equally important paths are unified in normal
      hemostasis, clotting at external bodily injury site is initiated for wound
      healing, but in intravascular injury 'blood clots' is formed to produce a disease
      called 'thrombosis'. As microthrombi from ULVWF path and fibrin clots from TF
      path become unified, macrothrombus would be formed via thrombogenesis. However,
      if ULVWF path and TF path cannot be unified due to lone ULVWF path activation,
      partial hemostasis produces only microthrombi seen in endotheliopathy-associated
      vascular microthrombotic disease. In real life, in-vivo fibrin clot cannot be
      formed alone via normal hemostasis because bleeding vascular injury always
      activates both ULVWF and TF paths. Without vascular injury, microthrombi due to
      activated ULVWF path occur in ADAMTS13 deficiency in thrombotic thrombocytopenic
      purpura, and fibrin clots due to activated TF path occur in acute promyelocytic
      leukemia. These two conditions can be called pathologic hemostasis. Three
      thrombogenic pathways produce three thrombotic disorders, which include
      macrothrombosis, microthrombosis and true DIC through macrothrombogenesis,
      microthrombogenesis and fibrinogenesis in both physiologic and pathological
      hemostasis.

PMID- 30234544
TI  - Reliability of the portable coagulometer qLabs to accurately measure the
      activated thromboplastin time and international normalized ratio: a prospective
      study in critically ill patients.
AB  - : The current prospective study was aimed at investigating whether a portable
      coagulometer (qLabs) can be used to reliably monitor activated thromboplastin
      time (aPTT) and international normalized ratio (INR) in critically ill patients,
      as compared with standard central laboratory measurement. Both precision and
      accuracy of INR and aPTT measured by qLabs were assessed in this observational
      study by finger prick group (N = 30 patients) and blood droplet group from
      central venous catheter drawn (N = 60). For accuracy, clinical agreement
      percentage was +/-0.3 for INR and +/-10 s for aPTT. Precision of INR measurement
      in qLabs showed excellent intraclass correlation coefficient (ICC > 90%).
      Precision of aPTT measurement in qLabs was less acceptable for both finger prick
      [ICC: 0.70; Bland-Altman plot: 2.2 s (-19.8, 24.2)] and blood droplet [ICC: 0.50;
      Bland-Altman plot: 0.4 s (-70.9, 71.8)] groups. Accuracy of qLabs was acceptable
      for INR assessment (clinical agreement 90 and 81%, for finger prick and blood
      droplet groups, respectively), but not for aPTT (clinical agreement 55 and 68%,
      respectively). Accuracy of finger prick and blood droplet measurements in qLabs
      was better for INR and aPTT values near-to-normal (1.2 and 37 s, respectively).
      INR values from qLabs were consistent with the 'gold standard'. qLabs measurement
      is only reliable for aPTT values near-to-normal.

PMID- 30234546
TI  - Sex, gender and venous thromboembolism: do we care enough?
AB  - : The role of sex and gender in determining clinical presentation, diagnostic
      approach and outcomes of venous thromboembolism is not fully and systematically
      addressed, except for hormone-related events in women. A lack of knowledge is
      also apparent regarding drug prescription patterns, physician bias, enrolment in
      clinical studies and analysis of sex-related confounders in preclinical and
      clinical studies. As was shown for cardiovascular disease, ignoring sex and
      gender in medicine can have important impact on outcomes, including mortality. In
      this review, we seek to address some aspects of venous thromboembolism such as
      epidemiology and clinical presentation, recurrence, risk factors, animal studies,
      safety and efficacy of antithrombotic drugs, highlighting what is known and what
      is not regarding the role of sex and gender, and hoping to focus some interest
      and to promote the inclusion of these variables in all future studies on venous
      thromboembolism.

PMID- 30234547
TI  - Delayed Death Due to Saddle Pulmonary Thromboembolus in Child With Nephrotic
      Syndrome Induced by Focal Segmental Glomerulosclerosis.
AB  - While the characteristic features of nephrotic syndrome (ie, proteinuria,
      hypoalbuminemia, peripheral edema, and hyperlipidemia) are well known, the
      association of nephrotic syndrome and the risk of thromboembolic events is not as
      often appreciated and may be overlooked. This report describes a 10-year-old boy
      with focal segmental glomerulosclerosis who died following a saddle pulmonary
      thromboembolus, with near-complete occlusion of the left and right pulmonary
      arteries. The gross appearance of the thrombus suggested organization and
      histologic changes within the wall of the pulmonary artery indicated a period of
      at least 3 or more hours to a few days since the event occurred. Pulmonary
      thromboemboli in children are rare, and the number of cases in the medical
      literature discussing the occurrence of pulmonary thromboemboli in the background
      of renal disease in children is relatively small, and none apparently clearly
      describe saddle thromboemboli with a delay from time of occurrence until death.
      This case report serves as a good reminder for forensic pathologists to consider
      renal disease as an underlying etiology for pulmonary thromboembolus and how
      histologic features of the pulmonary artery may help determine a time frame for
      the event.

PMID- 30234548
TI  - Diagnostic Criteria for Commotio Cordis Caused by Violent Attack: Review of the
      Literature.
AB  - The diagnosis of lethal commotio cordis (CC) is really complex. The forensic
      pathologist's task is even more relevant when he/she has to explain a CC
      diagnosis caused by an assault in a trial. The purpose of this study was to
      analyze the literature on lethal CC as a result of violent attacks and identify
      relevant parameters that may help in the diagnosis. A review of the relevant
      articles was performed. Fifty-two cases of CC caused by violent attacks were
      identified. The collected data allowed to confirm the following literature's
      criteria for CC diagnosis in case of assaults: witnessed occurrence of a blunt,
      nonpenetrating blow to the chest preceding cardiovascular collapse; absence of
      structural damage to the sternum, ribs, or heart itself; and absence of any
      underlying cardiovascular abnormalities (such as other causes of sudden death).
      Regarding the assessment of the third criterion, the authors suggest that the
      pathologist should always specify the scientific autopsy guidelines that he/she
      used to differentiate CC from the other causes of sudden death. In addition, the
      authors highlight the importance of a multidisciplinary approach for a correct
      interpretation of clinical, autopsy, and laboratory findings.

PMID- 30234549
TI  - Nurse and Nurse Student Attitudes and Perceived Self-efficacy in Use of
      Information and Communication Technologies: Professional and Cultural
      Differences.
AB  - Information and communication technologies have become essential and design
      effective tools in the global healthcare system. Evidence suggests that
      information and communication technologies can promote nursing practice and
      patient satisfaction and quality of care. Competency with information and
      communication technologies is essential for both nurses and nursing students, and
      attitudes toward its use and perceived self-efficacy are important for
      implementation in the workplace. This study aimed to explore nurse and nursing
      student attitudes and perceived self-efficacy regarding information and
      communication technologies use in clinical practice and to examine professional
      and cultural differences between these groups in their attitudes and perceived
      self-efficacy in information and communication technologies use. A cross
      sectional study was conducted among Israeli nursing students (n = 144) and
      registered nurses (n = 104). The findings revealed that respondents held overall
      positive attitudes toward information and communication technologies' use in
      clinical practice and perceived themselves as competent in this context.
      Significant differences were found between nurses and students in their attitudes
      toward information and communication technologies and information and
      communication technologies self-efficacy. Cultural group (Jewish/Arab) was found
      related to positive attitudes toward use of information and communication
      technologies in clinical practice. Nurse educators and managers should be aware
      of the potential impact of cultural and professional differences on the adoption
      and implementation of information and communication technologies and should
      institute initiatives within the organization and academia to manage cultural and
      professional discrepancies.

PMID- 30234551
TI  - Periorbital Edema as the Initial Sign of Juvenile Dermatomyositis.

PMID- 30234550
TI  - Dynamic Prediction of Survival in Cystic Fibrosis: A Landmarking Analysis Using
      UK Patient Registry Data.
AB  - BACKGROUND: Cystic fibrosis (CF) is an inherited, chronic, progressive condition
      affecting around 10,000 individuals in the United Kingdom and over 70,000
      worldwide. Survival in CF has improved considerably over recent decades, and it
      is important to provide up-to-date information on patient prognosis. METHODS: The
      UK Cystic Fibrosis Registry is a secure centralized database, which collects
      annual data on almost all CF patients in the United Kingdom. Data from 43,592
      annual records from 2005 to 2015 on 6181 individuals were used to develop a
      dynamic survival prediction model that provides personalized estimates of
      survival probabilities given a patient's current health status using 16
      predictors. We developed the model using the landmarking approach, giving
      predicted survival curves up to 10 years from 18 to 50 years of age. We compared
      several models using cross-validation. RESULTS: The final model has good
      discrimination (C-indexes: 0.873, 0.843, and 0.804 for 2-, 5-, and 10-year
      survival prediction) and low prediction error (Brier scores: 0.036, 0.076, and
      0.133). It identifies individuals at low and high risk of short- and long-term
      mortality based on their current status. For patients 20 years of age during 2013
      2015, for example, over 80% had a greater than 95% probability of 2-year survival
      and 40% were predicted to survive 10 years or more. CONCLUSIONS: Dynamic
      personalized prediction models can guide treatment decisions and provide
      personalized information for patients. Our application illustrates the utility of
      the landmarking approach for making the best use of longitudinal and survival
      data and shows how models can be defined and compared in terms of predictive
      performance.

PMID- 30234552
TI  - Risk stratification for complex ventricular arrhythmia complicating ST-segment
      elevation myocardial infarction.
AB  - OBJECTIVES: The primary aim of the study was to evaluate risk factors for
      ventricular fibrillation/sustained ventricular tachycardia (VF/VT) and to develop
      the risk score for prediction of VF/VT in patients with ST-segment elevation
      myocardial infarction (STEMI) treated invasively. The secondary aim was to assess
      the effect of VF/VT on mortality depending on timing of arrhythmia. PATIENTS AND
      METHODS: We analyzed 4363 consecutive patients with STEMI treated invasively.
      Among them, 163 patients with pre-reperfusion arrhythmia were excluded from the
      study. Group ventricular arrhythmias (VA) encompassed patients with VF/VT - those
      with reperfusion-induced arrhythmia were included into group VA1, whereas group
      VA2 consisted of patients with postreperfusion arrhythmia. The control group
      comprised patients free of VF/VT. RESULTS: VF or VT occurred in 313 (7.45%)
      patients - group VA1 encompassed 103 (32.9%) and group AV2 210 (67.1%) patients.
      Cardiogenic shock on admission [hazard ratio (HR) 3.5], new-onset atrial
      fibrillation (HR 2.1), incomplete revascularization (HR 1.7), prior myocardial
      infarction (HR 1.6) and symptom-to-balloon time more than 3 h (HR 1.3) were the
      independent predictors of VF/VT occurrence. In group VA2, the in-hospital and
      long-term mortality were 4- and 1.5-fold higher than in the arrhythmia-free
      population (20.5 vs. 4.5% and 36.2 vs. 22.6%, respectively; P<0.001). On the
      contrary, in group VA1, the long-term mortality was not significantly higher
      compared with the control group (26.2 vs. 22.6%; P=NS), whereas in-hospital
      mortality was almost three-fold increased (12.5 vs. 4.5%, respectively; P<0.001).
      CONCLUSION: The risk score based on simple clinical parameters might be useful
      for risk stratification for VF/VT in patients with STEMI. The predictive value of
      VF/VT was strongly dependent on timing of arrhythmia.

PMID- 30234554
TI  - Metabolism: The road to inflammation and atherosclerosis.
AB  - PURPOSE OF REVIEW: Evidence accumulates suggesting that cellular metabolic
      alterations fuel and dictate the inflammatory state of cells. In this review, we
      provide an overview of the observed metabolic reprogramming in endothelial cells
      and innate immune cells upon interaction with modified lipoproteins, thereby
      contributing to the progression of atherosclerosis. RECENT FINDINGS: Inflammatory
      endothelial cells at sites exposed to disturbed flow patterns show increased
      glycolytic activity. Atherogenic factors further enhance these metabolic changes
      by upregulating the mitochondrial energy production and thereby facilitating
      increased energy expenditure. Metabolic alterations are pivotal for monocyte and
      macrophage function as well. Exposure to atherogenic particles such as oxidized
      phospholipids lead to a regulatory metabolic pro-inflammatory phenotype, mediated
      via Toll-like receptor (TLR) 2 and the transcription factor erythroid 2-related
      factor (Nrf) 2. Translational studies highlighted the importance of metabolic
      alterations, as atherosclerotic plaques in the carotid arteries showed an
      increased glycolytic signature. SUMMARY: Alterations in cellular metabolism play
      an important role in controlling and steering the inflammatory state of both
      endothelial cells and immune cells. Targeting glycolysis may therefore provide an
      interesting route to attenuate the progression of atherosclerosis.

PMID- 30234555
TI  - RNA-targeted therapeutics for lipid disorders.
AB  - PURPOSE OF REVIEW: To summarize recent developments in the field of RNA-directed
      therapeutics targeting lipid disorders that are not effectively managed. RECENT
      FINDINGS: Despite a number of approved therapies for lipid disorders, significant
      unmet needs are present in treating persistently elevated LDL-cholesterol,
      remnant-cholesterol, triglycerides and lipoprotein(a) [Lp(a)]. Small molecules
      and antibodies are effective modalities, but they are unable to adequately treat
      many patients with abnormal lipid parameters. Targeting mRNA with
      oligonucleotides to prevent protein translation is a relatively novel method to
      reduce circulating atherogenic lipoproteins. Small inhibiting RNA (siRNA)
      molecules targeting proprotein convertase subtilisin kexin type 9 to reduce LDL
      C, and antisense oligonucleotides (ASO) targeting apolipoprotein C-III (apoC-III)
      to reduce triglycerides, angiopoietin-like 3 (ANGPTL3) to reduce LDL-C and
      triglycerides and apolipoprotein(a) (LPA) to reduce Lp(a) are currently in or
      just completed phase 1-3 trials. Fundamental differences exist in chemistry,
      delivery and mechanism of action of siRNA and ASOs. SUMMARY: Novel RNA
      therapeutics are poised to provide highly potent, specific and effective
      therapies to reduce atherogenic lipoproteins. As these compounds are approved,
      clinicians will be able to choose from a broad armamentarium to treat nearly all
      patients to acceptable goals in order to reduce risk of cardiovascular disease
      and events.

PMID- 30234553
TI  - Establishment of a multicomponent dietary bioactive human equivalent dose to
      delete damaged Lgr5+ stem cells using a mouse colon tumor initiation model.
AB  - Multicomponent therapy has gained interest for its potential to synergize and
      subsequently lower the effective dose of each constituent required to reduce
      colon cancer risk. We have previously showed that rapidly cycling Lgr5 stem cells
      are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer
      risk. In the present study, we quantified the dose-dependent synergistic
      properties of dietary n-3 polyunsaturated fatty acids (PUFA) and curcumin (Cur)
      to promote targeted apoptotic deletion of damaged colonic Lgr5 stem cells. For
      this purpose, both heterogeneous bulk colonocytes and Lgr5 stem cells were
      isolated from Lgr5-EGFP-IRES-CreER knock-in mice injected with azoxymethane
      (AOM). Isolated cells were analyzed for DNA damage (gammaH2AX), apoptosis
      (cleaved caspase-3), and targeted apoptosis (both gammaH2AX and cleaved caspase
      3) at 12 h post-AOM injection. Comparison of the percentage of targeted apoptosis
      in Lgr5 stem cells (GFP) across a broad bioactive dose-range revealed an ED50 of
      16.0 mg/day n-3 PUFA+15.9 mg/day Cur. This corresponded to a human equivalent
      dose of 3.0 g n-3 PUFA+3.0 g Cur. In summary, our results provide evidence that a
      low dose (n-3 PUFA+Cur) combination diet reduces AOM-induced DNA damage in Lgr5
      stem cells and enhances targeted apoptosis of DNA-damaged cells, implying that a
      lower human equivalent dose can be utilized in future human clinical trials.

PMID- 30234556
TI  - The prediction of therapy-benefit for individual cardiovascular disease
      prevention: rationale, implications, and implementation.
AB  - PURPOSE OF REVIEW: We aim to outline the importance and the clinical implications
      of using predicted individual therapy-benefit in making patient-centered
      treatment decisions in cardiovascular disease (CVD) prevention. Therapy-benefit
      concepts will be illustrated with examples of patients undergoing lipid
      management. RECENT FINDINGS: In both primary and secondary CVD prevention, the
      degree of variation in individual therapy-benefit is large. An individual's
      therapy-benefit can be estimated by combining prediction algorithms and clinical
      trial data. Measures of therapy-benefit can be easily integrated into clinical
      practice via a variety of online calculators. Lifetime estimates (e.g., gain in
      healthy life expectancy) look at therapy-benefit over the course of an
      individual's life, and are less influenced by age than short-term estimates
      (e.g., 10-year absolute risk reduction). Lifetime estimates can thus identify
      people who could substantially benefit from early initiation of CVD prevention.
      Compared with current guidelines, treatment based on predicted therapy-benefit
      would increase eligibility for therapy among young people with a moderate risk
      factor burden and individuals with a high residual risk. SUMMARY: The estimation
      of individual therapy-benefit is an important part of individualized medicine.
      Implementation tools allow for clinicians to readily estimate both short-term and
      lifetime therapy-benefit.

PMID- 30234557
TI  - Can epinephrine therapy be detrimental to patients with hypertrophic
      cardiomyopathy with hypotension or cardiac arrest? a systematic review.
AB  - Approximately 10% of sudden cardiac deaths among patients under 35 years of age
      is owing to hypertrophic cardiomyopathy (HCM)-related cardiac arrest (CA). CA is
      often associated with pre-arrest or peri-arrest hypotension and is treated by a
      set of interventions, including the administration of epinephrine. It is debated
      whether epinephrine increases or decreases survival to discharge following CA.
      HCM is associated with septal hypertrophy with a dynamic left ventricular outflow
      tract obstruction and impaired peripheral vasoconstriction in response to alpha1
      adrenergic stimulation, both of which could cause epinephrine to have a different
      effect than in the general population. This systematic review of the literature
      aimed to investigate if patients with HCM in CA have a detrimental hemodynamic
      response to epinephrine. A literature search was performed in October 2016 using
      Medline (OVID), Embase (Elsevier), and Cochrane Library (Wiley). The initial
      search generated 2429 articles, of which 22 articles were found to meet inclusion
      criteria: four physiology studies, 13 case reports of hypotensive HCM patients,
      and five case reports of HCM patients in CA. The reviewed studies demonstrate
      that epinephrine effect varies in patients with HCM: in some cases, the expected
      hypertensive effect was obtained, but in others, a paradoxical hypotensive
      effect, or no effect, was observed. The probable mechanism of this effect is an
      increased left ventricular outflow tract obstruction. Other drugs were considered
      in several of these cases. In summary, the retrieved studies jointly suggest that
      patients with HCM may respond differently to epinephrine than patients without
      HCM. The suitability of epinephrine in HCM-associated CA is questionable.

PMID- 30234558
TI  - Natalizumab Treatment for Relapsing-Remitting Multiple Sclerosis: The Experience
      From Saudi Arabia.
AB  - BACKGROUND: Natalizumab is the first targeted humanized monoclonal antibody to be
      approved for the treatment of relapsing-remitting multiple sclerosis (RRMS).
      Natalizumab appears to be more effective than current first-line disease
      modifying therapies. In our study, we aimed to evaluate the outcome of Saudi
      patients with active RRMS treated with natalizumab and compare the results with
      other outcomes in the Gulf and international trials. METHODS: We conducted a
      retrospective single-center observational study involving 32 patients with RRMS
      at King Abdulaziz Medical City in Jeddah, Saudi Arabia. The inclusion criteria
      included all patients diagnosed with RRMS according to the revised McDonald
      criteria who are currently receiving or received natalizumab treatment in the
      past for a minimum of 6 months. RESULTS: The mean baseline Expanded Disability
      Status Scale score was 4.50 +/- 1.80 (range, 1.5-6; median, 5), whereas the mean
      Expanded Disability Status Scale at the follow-up was 4.02 +/- 2.08 (range, 1-6;
      median, 4.25) (P = 0.3274). The mean annualized relapse rate was significantly
      reduced from 2.41 +/- 2.48 at baseline to 0.16 +/- 0.37 at the last follow-up (P
      < 0.0001). Twenty-seven patients (84.4%) had no relapses since the treatment with
      natalizumab was started, whereas 5 patients (15.6%) had only 1 relapse. In
      addition to clinically measurable improvement, radiological improvement was
      observed through magnetic resonance imaging. Magnetic resonance imaging activity
      was significantly improved at follow-up magnetic resonance imaging studies when
      compared with baseline. CONCLUSIONS: Our single-center study in Saudi Arabia
      provides further support for the efficacy of natalizumab in the clinical practice
      setting. The sharp decrease in relapse rate and progression of disability
      following the initiation of natalizumab treatment was similar to other
      observational studies conducted in different countries across the globe.
      Natalizumab was a satisfactory therapy for the management of our MS population,
      both from the patients' and the physicians' perspectives.

PMID- 30234559
TI  - Levetiracetam-Induced Seizure Aggravation in Patients With Focal Cortical
      Dysplasia.
AB  - OBJECTIVES: The choice of antiepileptic drug is typically based on seizure type,
      and there is no evidence for superior effectiveness or potential deterioration of
      particular antiepileptic drug in specific etiologic subgroups. The aim of the
      study was to identify etiological factor(s) associated with increased risk of
      seizure aggravation with levetiracetam (LEV). METHODS: A retrospective analysis
      of 139 patients treated with LEV was performed. Seizure aggravation was defined
      as a 100% or greater increase in seizures frequency, which occurred within 1
      month of drug introduction. RESULTS: Five patients who fulfilled the selection
      criteria were identified. Seizure aggravation occurred with low doses (500-1000
      mg) of LEV. In addition to increased frequency and duration, 2 patients developed
      new seizure types. Withdrawal of LEV resulted in seizure return to background
      frequency in all patients. Four of 5 patients have distinctive magnetic resonance
      imaging finding of focal cortical dysplasia. No patients with paradoxical effect
      of LEV were detected in the idiopathic epilepsy group or other types of
      symptomatic epilepsies. CONCLUSIONS: Our results suggest that LEV may possibly
      induce seizure exacerbation in a subset of patients with focal cortical dysplasia
      related epilepsy, although large studies are needed to establish the relation.
      Underlying causes of epilepsy could impact the treatment choice because
      electroclinical semiology might be the "final common pathway" of different
      epileptogenic mechanisms in diverse etiologies.

PMID- 30234560
TI  - "Extramammary-Type" Paget Disease of the Breast.
AB  - BACKGROUND: Mammary Paget disease and extramammary Paget disease (EMPD) have
      different prognoses. Because they are indistinguishable on histopathological
      grounds, they must be distinguished on a topographical basis. OBJECTIVE: To study
      cases of Paget disease of the breast, which show similarities to EMPD. METHODS:
      Cases were selected by 2 different approaches: (1) those with an exceptionally
      good evolution and no evidence of subjacent tumor and (2) those expressing
      MUC5AC. RESULTS: Five cases were collected. All cases showed an indolent behavior
      with a known long clinical history in 2 cases (9 and 25 years, respectively) and
      a long follow-up in all cases but one (4-8 years). In all cases but one, surgery
      was performed, and no parenchymal tumor was found (either intraductal or
      infiltrating). All cases expressed cytokeratin 7 and MUC5AC without expression of
      MUC2, S100, or p40. LIMITATIONS: The short number of cases is a limitation of
      this study. In addition, case 5 is recent, so we have a very short follow-up.
      CONCLUSIONS: Some cases of mammary Paget disease behave like EMPD with slow
      progression and with no underlying associated tumor. Immunoexpression of MUC5AC
      might be a clue to identify them.

PMID- 30234561
TI  - Facial Follicular Cyst and Cicatricial Alopecia: Answer.

PMID- 30234562
TI  - Psoriasiform, Hyperpigmented Plaques of the Palms and Soles: Answer.

PMID- 30234563
TI  - Papulonodular Eruption on the Hands in a Patient With Arthritis: Answer.

PMID- 30234564
TI  - A 32-Year-Old Woman With Tender Nodules That Ulcerate: Challenge.

PMID- 30234565
TI  - How to Write an Effective Introduction.
AB  - Ideally, the Introduction is an essential attention grabbing section of a
      research paper. If written correctly, the Introduction peaks the reader's
      interest as well as serves as a roadmap for the rest of the paper. An effective
      Introduction builds off related empirical research and demonstrates a gap in
      which the current study fills. Finally, the Introduction proposes the research
      question(s) which will be answered in subsequent sections of the paper. A strong
      Introduction also requires the use of a simple and well-organized format as well
      as the avoidance of common pitfalls.

PMID- 30234566
TI  - Radiographic and CT Evaluation of Recombinant Human Bone Morphogenetic Protein-2
      assisted Cervical Spinal Interbody Fusion.
AB  - STUDY DESIGN: This was a retrospective study. OBJECTIVE: To radiographically
      demonstrate the distinct fusion pattern of recombinant human bone morphogenetic
      protein-2 (rhBMP-2) in the setting of anterior cervical discectomy and fusion.
      SUMMARY OF BACKGROUND DATA: Studies investigating spinal fusion assisted with
      rhBMP-2 have yielded promising results, suggesting rhBMP-2 is an efficacious
      alternative to iliac crest autografts. rhBMP-2-assisted spinal fusion both
      hastens healing and eliminates patient morbidity from iliac crest autograft.
      Unique to rhBMP-assisted spinal fusion is its distinct radiographic fusion
      pattern as fusion is achieved. Despite promising results and increased clinical
      use of rhBMP-2, there remains a paucity of literature documenting this
      radiographic process. MATERIALS AND METHODS: This study included 26 patients who
      underwent single-level anterior cervical discectomy and fusion using rhBMP-2. All
      data used for this study was collected from a prior FDA Investigational Device
      Exemption study. RESULTS: A polyetheretherketone cage was used as an interbody
      disk spacer in all 26 patients. Patients were evaluated between 2 and 6 weeks
      after surgery and subsequently at 3, 6, 12, and 24 months postoperative. All
      patients underwent plain radiography at every follow-up visit, and computed
      tomograhy evaluation was performed at 3, 6, 12, and 24 months as part of the
      study protocol. Earliest fusion was observed at 3 months in 38% of patients.
      Likely fusion was observed in all patients by 12 months postoperative.
      CONCLUSIONS: rhBMP-2 leads to both successful interbody fusion and an enhanced
      fusion rate with unique imaging characteristics. Additional characteristics of
      BMP observed in 100% of patients included prevertebral soft-tissue swelling and
      early endplate resorption. Other common features included polyetheretherketone
      cage migration, heterotopic bone formation and cage subsidence.

PMID- 30234567
TI  - The Effect of Preoperative Medications on Length of Stay, Inpatient Pain, and
      Narcotics Consumption After Minimally Invasive Transforaminal Lumbar Interbody
      Fusion.
AB  - STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: To determine the
      association between preoperative medications and length of stay, inpatient pain,
      and narcotics consumption after a minimally invasive transforaminal lumbar
      interbody fusion (MIS TLIF). SUMMARY OF BACKGROUND DATA: Previous studies have
      identified risk factors for increased length of hospital stay, inpatient pain,
      and narcotics consumption. However, little is known regarding the effects of
      preoperative medications on outcomes after spine surgery. METHODS: A
      prospectively maintained surgical database of patients undergoing primary, single
      level MIS TLIF was retrospectively reviewed. Preoperative medications taken
      within 30 days before surgery were recorded for each patient and categorized by
      medication type. Poisson regression with robust error variance was used to
      determine the association between preoperative medications and length of stay,
      pain scores, and narcotics consumption. Multivariate analysis was performed using
      a backwards, stepwise regression to identify independent risk factors. RESULTS:
      In total, 138 patients were included in this analysis. On bivariate analysis,
      benzodiazepines were associated with longer hospital stays [relative risk
      (RR)=2.03; P=0.031]. Benzodiazepines (RR=3.71; P<0.001) and preoperative
      narcotics (RR=2.60; P=0.012) were risk factors for pain >=7 on postoperative day
      0. On multivariate analysis, benzodiazepines were an independent risk factor for
      prolonged stay. Benzodiazepines, narcotics, and nonsteroidal anti-inflammatories
      were identified as independent risk factors for increased postoperative pain.
      CONCLUSIONS: These results suggest that benzodiazepines are a risk factor for
      increased length of stay and postoperative pain after MIS TLIF. Preoperative
      narcotics and nonsteroidal anti-inflammatories were also identified as risk
      factors for postoperative pain though this did not lead to increases in narcotics
      consumption. Patients taking these medications should undergo more vigilant
      perioperative monitoring for adequate pain management. More work must be done to
      further elucidate the association between preoperative medications and
      postoperative outcomes after MIS TLIF.

PMID- 30234568
TI  - The Effects of Storage Age of Blood in Massively Transfused Burn Patients: A
      Secondary Analysis of the Randomized Transfusion Requirement in Burn Care
      Evaluation Study.
AB  - OBJECTIVES: Major trials examining storage age of blood transfused to critically
      ill patients administered relatively few blood transfusions. We sought to
      determine if the storage age of blood affects outcomes when very large amounts of
      blood are transfused. DESIGN: A secondary analysis of the multicenter randomized
      Transfusion Requirement in Burn Care Evaluation study which compared restrictive
      and liberal transfusion strategies. SETTING: Eighteen tertiary-care burn centers.
      PATIENTS: Transfusion Requirement in Burn Care Evaluation evaluated 345 adults
      with burns greater than or equal to 20% of the body surface area. We included
      only the 303 patients that received blood transfusions. INTERVENTIONS: The
      storage ages of all transfused red cell units were collected during Transfusion
      Requirement in Burn Care Evaluation. A priori measures of storage age were the
      the mean storage age of all transfused blood and the proportion of all transfused
      blood considered very old (stored >= 35 d). MEASUREMENTS AND MAIN RESULTS: The
      primary outcome was the severity of multiple organ dysfunction. Secondary
      outcomes included time to wound healing, the duration of mechanical ventilation,
      and in-hospital mortality. There were 6,786 red cell transfusions with a mean (+/
      SD) storage age of 25.6 +/- 10.2 days. Participants received a mean of 23.4 +/-
      31.2 blood transfusions (range, 1-219) and a mean of 5.3 +/- 10.7 units of very
      old blood. Neither mean storage age nor proportion of very old blood had any
      influence on multiple organ dysfunction severity, time to wound healing, or
      mortality. Duration of ventilation was significantly predicted by both mean blood
      storage age and the proportion of very old blood, but this was of questionable
      clinical relevance given extreme variability in duration of ventilation (adjusted
      r <= 0.01). CONCLUSIONS: Despite massive blood transfusion, including very old
      blood, the duration of red cell storage did not influence outcome in burn
      patients. Provision of the oldest blood first by Blood Banks is rational, even
      for massive transfusion.

PMID- 30234569
TI  - Incidence and Prevalence of Delirium Subtypes in an Adult ICU: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVES: Use systematic review and meta-analytic methodology to estimate the
      pooled incidence, prevalence, and proportion of delirium cases for each delirium
      subtype (hypoactive, hyperactive, and mixed) in an adult ICU population. DATA
      SOURCES: We conducted a search of the MEDLINE, EMBASE, CINAHL, SCOPUS, Web of
      Science, and PsycINFO databases following the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses standards from database inception until
      October 22, 2017, with no restrictions. STUDY SELECTION: We included original
      research conducted in adults admitted to any medical, surgical, or speciality ICU
      that reported incidence or prevalence estimates of delirium according to delirium
      subtype. DATA EXTRACTION: Data were extracted on sample size, population
      demographics, condition information, and reported delirium estimates. DATA
      SYNTHESIS: Forty-eight studies (27,342 patients; 4,550 with delirium) with an
      overall pooled prevalence of 31% (95% CI, 24-41; I = 99%) met inclusion criteria.
      The pooled incidence (n = 18 studies) of delirium subtypes were hyperactive (4%
      [95% CI, 2-6]; I = 92%]), hypoactive (11% [95% CI, 8-17; I = 97%]), and mixed (7%
      [95% CI, 4-11; I = 97%]). The pooled prevalence (n = 31 studies) of delirium
      subtypes were hyperactive (4% [95% CI, 3-6; I = 94%]), hypoactive (17% [95% CI,
      13-22; I = 97%]), and mixed (10% [95% CI, 6-16; I = 99%]). The pooled prevalence
      of hypoactive delirium in study populations with a similarly high severity of
      illness or mechanically ventilated was higher (severity of illness: 29% [95% CI,
      18-46%; I = 95%], 100% mechanically ventilated: 35% [95% CI, 23-55%; I = 93%])
      compared with the pooled prevalence of hypoactive delirium. CONCLUSIONS: Despite
      significant heterogeneity between studies, these data show the majority of
      delirious ICU patients to have hypoactive delirium, a finding with potential
      monitoring, management, and prognostic implications. The prevalence of hypoactive
      delirium varies between-study populations and is higher in patients with greater
      severity of illness.

PMID- 30234570
TI  - Scleroderma and Person/Patient-Centered Concerns.

PMID- 30234571
TI  - From the Editors' Desk.

PMID- 30234572
TI  - Compliance Tips to Prevent Claim Denials: Part 4, Reporting Diagnosis Codes.

PMID- 30234573
TI  - Patient Transfer Devices.

PMID- 30234574
TI  - Advances in Upper Extremity Scleroderma Wound Care.
AB  - GENERAL PURPOSE: To provide information about the pathophysiology, diagnosis, and
      treatment options for systemic sclerosis. TARGET AUDIENCE: This continuing
      education activity is intended for physicians, physician assistants, nurse
      practitioners, and nurses with an interest in skin and wound care. LEARNING
      OBJECTIVES/OUTCOMES: After participating in this educational activity, the
      participant should be better able to:1. Describe the pathophysiology, signs,
      symptoms, and diagnosis of systemic sclerosis.2. Outline the evidence-based
      medical and surgical management of systemic sclerosis. ABSTRACT: OBJECTIVE:: To
      perform a targeted review of systemic sclerosis, including epidemiology,
      pathophysiology, diagnosis, signs and symptoms, and medical and surgical
      management of upper extremity manifestations. DATA SOURCES AND STUDY SELECTION:
      An electronic literature review was conducted using PubMed for all publication
      dates through October 2017. Searches were performed using combinations of terms
      including "systemic sclerosis," "scleroderma," "management," "upper extremity,"
      "hypercalcinosis," "Raynaud's phenomenon," "sympathectomy," and "digital ulcers."
      Only full-length articles written in English that discussed the management of
      upper extremity scleroderma were used. DATA EXTRACTION AND SYNTHESIS: The
      epidemiology, pathophysiology, diagnosis, upper extremity manifestations, and
      medical and surgical management of systemic sclerosis were reviewed. The case
      described in this article reports the utility of microsurgical interventions in
      the treatment of medically refractory upper extremity systemic sclerosis.
      CONCLUSIONS: Systemic sclerosis is a rare rheumatologic disease that greatly
      impacts quality of life. Medical management is the mainstay of treatment,
      propelling an improvement in the dismal 10-year cumulative survival rate from 54%
      in the 1970s to 66% in the 1990s. However, the pathophysiology of this disease is
      still poorly understood, and when medical management fails and the disease
      inevitably progresses, surgical approaches are critical.

PMID- 30234575
TI  - Pressure Injury in the Pediatric Population: Cohort Study Using the Braden Q
      Scale.
AB  - OBJECTIVE: To identify the risk and incidence of pressure injuries in bedridden
      pediatric patients to determine the most prevalent risk factors and preventive
      measures and to define the sociodemographic, clinical, and therapeutic profiles
      in this group. METHODS: Prospective cohort study performed between March 2015 and
      March 2016 in the intensive care unit and the pediatric ward of a public teaching
      hospital. The study included 85 pediatric patients (45 intensive care unit and 40
      pediatric ward patients). MAIN OUTCOME MEASURE: Patients' Braden Q Scale score
      was assessed at 48-hour intervals until discharge from the aforementioned units,
      discharge from the hospital, and/or death. MAIN RESULTS: Researchers observed
      that 93.3% of intensive care unit patients and 87.5% of pediatric ward patients
      were categorized as high-risk patients, and 12 patients presented with 24
      pressure injuries with an incidence of 14.1% and a mean of 4 days before pressure
      injury occurrence. Patients with pressure injuries in the cohort averaged a
      hospital length of stay of 7.7 days. Of these, the mean age was 4.1 years and
      most were female, receiving enteral nutrition, and had diagnoses related to
      neurological and respiratory diseases.' Vasopressor use had a statistically
      significant association (P < .05) with the development of pressure injuries. The
      primary risk factor identified on the Braden Q Scale for the development pressure
      injury was a "mobility and activity" deficit. CONCLUSIONS: Most patients
      (hospitalized in either unit) were at high risk of developing pressure injuries.
      No specific preventive guidelines were in place in this hospital prior to this
      study; therefore, the authors aimed to develop a protocol for the prevention and
      reduction of pressure injuries in pediatric patients.

PMID- 30234576
TI  - Effectiveness of Transcutaneous Electrical Nerve Stimulation Energy in Older
      Adults: A Pilot Clinical Trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a transcutaneous electric nerve
      stimulation (TENS) device typically used for pain suppression (analgesia) during
      pressure injury (PI) healing, peripheral vascularization, and secondary pain in
      older adults with chronic PIs and cognitive impairment. DESIGN AND SETTING: This
      pilot clinical trial followed patients from 6 nursing homes. PATIENTS AND
      INTERVENTION: Twenty-two patients with PIs in the distal third of their lower
      limbs (7 men, 15 women) were included in this study. The control group completed
      standard wound care (SWC), whereas the experimental group received SWC and TENS.
      A total of 20 sessions were conducted for each group over 2 months, 3 times a
      week. MAIN OUTCOME MEASURE: PI area, PI healing rate, blood flow, skin
      temperature, oxygen saturation, and level of pain at baseline and posttreatment.
      MAIN RESULTS: Significant improvements were achieved in PI area (mean difference,
      0.92; 95% confidence interval [CI], 0.15-1.67; P =.024), healing rate (3; 95% CI,
      1-4.99; P =.009), skin temperature (1.82; 95% CI, 0.35-3.28; P =.021), and pain
      (1.44; 95% CI, 0.49-2.39; P =.008) in the experimental group, whereas none of the
      variables revealed a significant change in the control group. CONCLUSIONS: The
      effect of local and spinal TENS combined with the SWC for PI produced a
      significant improvement in size, healing, skin temperature, and pain levels.

PMID- 30234578
TI  - Wound Care Medical Record Documentation.

PMID- 30234577
TI  - The Impact of Surgical Wound Dehiscence on Body Image.
AB  - OBJECTIVE: To identify changes in body image in patients with surgical wound
      dehiscence. DESIGN AND SETTING: This cross-sectional, descriptive, analytical
      study was conducted in a university hospital and nursing care center in Brazil.
      PATIENTS AND INTERVENTION: Sixty-one adult surgical patients of both genders from
      different inpatient wards or receiving outpatient care were selected. Forty-one
      participants had surgical wound dehiscence, and 20 had achieved complete wound
      healing (controls). MAIN OUTCOME MEASURE: The Body Dysmorphic Disorder
      Examination (BDDE), Body Investment Scale (BIS), and a questionnaire assessing
      clinical and sociodemographic characteristics of patients were used for data
      collection. MAIN RESULTS: Surgical wound dehiscence defects were 0.5 to 30 cm in
      length, located on the arms, legs, and chest. They were significantly associated
      with being white (P = .048), number of children (P = .024), and presence of
      comorbid conditions (P = .01). Overall, men reported higher BIS scores (positive
      feelings about the body) than women (P = .035). Patients with wound dehiscence
      had higher BDDE scores (negative body image) than controls (P = .013). The BDDE
      scores were associated with presence of surgical wound dehiscence (P = .013),
      number of children (P = .009), and wound length (P = .02). There were significant
      correlations between BIS scores in men with wound dehiscence (P = .042), number
      of children (P < .001), and BDDE scores (P < .001) and between BDDE scores and
      number of children (P = .031), wound length (P = .028), and BIS scores (P <
      .001). CONCLUSION: Surgical wound dehiscence had a negative impact on body image.

PMID- 30234579
TI  - Advances in Upper Extremity Scleroderma Wound Care.

PMID- 30234583
TI  - This Month in Anesthesiology.

PMID- 30234585
TI  - Machine Learning for Anesthesiologists: A Primer.

PMID- 30234580
TI  - Prediction Score for Postoperative Neurologic Complications after Brain Tumor
      Craniotomy: A Multicenter Observational Study.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
      BACKGROUND:: Craniotomy for brain tumor displays significant morbidity and
      mortality, and no score is available to discriminate high-risk patients. Our
      objective was to validate a prediction score for postoperative neurosurgical
      complications in this setting. METHODS: Creation of a score in a learning cohort
      from a prospective specific database of 1,094 patients undergoing elective brain
      tumor craniotomy in one center from 2008 to 2012. The validation cohort was
      validated in a prospective multicenter independent cohort of 830 patients from
      2013 to 2015 in six university hospitals in France. The primary outcome variable
      was postoperative neurologic complications requiring in-intensive care unit
      management (intracranial hypertension, intracranial bleeding, status epilepticus,
      respiratory failure, impaired consciousness, unexpected motor deficit). The least
      absolute shrinkage and selection operator method was used for potential risk
      factor selection with logistic regression. RESULTS: Severe complications occurred
      in 125 (11.4%) and 90 (10.8%) patients in the learning and validation cohorts,
      respectively. The independent risk factors for severe complications were related
      to the patient (Glasgow Coma Score before surgery at or below 14, history of
      brain tumor surgery), tumor characteristics (greatest diameter, cerebral midline
      shift at least 3 mm), and perioperative management (transfusion of blood
      products, maximum and minimal systolic arterial pressure, duration of surgery).
      The positive predictive value of the score at or below 3% was 12.1%, and the
      negative predictive value was 100% in the learning cohort. In-intensive care unit
      mortality was observed in eight (0.7%) and six (0.7%) patients in the learning
      and validation cohorts, respectively. CONCLUSIONS: The validation of prediction
      scores is the first step toward on-demand intensive care unit admission. Further
      research is needed to improve the score's performance before routine use.

PMID- 30234587
TI  - From Horse to Hearse: Tragedy Strikes Laughing-gas Dentist Charles Henry Neall.

PMID- 30234588
TI  - How Two Longfellows Revered Ether.

PMID- 30234589
TI  - Birth Centennial of Nobel Laureate Skou, an Investigator of Local Anesthetics and
      the Sodium-Potassium Pump.

PMID- 30234590
TI  - Ohmeda Slide Rule for Pressures and Volumes.

PMID- 30234592
TI  - From "Bagging" Patients to Bagging Dr. Heidbrink, Maker of Anesthesia Machines.

PMID- 30234591
TI  - Images in Anesthesiology: Persistent Pulmonary Interstitial Emphysema.

PMID- 30234593
TI  - Haunted Anesthesia? Spirited Herbs in Mayo's Vegetable Vapor.

PMID- 30234594
TI  - Questions about the Practice Management Guidelines for Moderate Sedation and
      Analgesia.

PMID- 30234595
TI  - In Reply.

PMID- 30234596
TI  - Team Approach: Clinical Outcome Collection, Done Practically.

PMID- 30234597
TI  - Periprosthetic Infections of the Shoulder.

PMID- 30234598
TI  - Drug abuse and HIV-related pulmonary hypertension: double hit injury.
AB  - : Improved survival among HIV-1-infected individuals with the advent of
      antiretroviral therapy has clearly led to a greater prevalence of noninfectious
      complications. One of the most devastating sequelae in these individuals is the
      development of pulmonary arterial hypertension (PAH). Various epidemiological
      studies suggest worse survival of HIV-PAH patients when compared with other forms
      of PAH. Given that only a subset and not all HIV-infected individuals develop HIV
      PAH, it is suggested that an additional second-hit of genetic or environmental
      trigger is needed for the development of PAH. In this context, it has been well
      documented that HIV patients who abuse illicit drugs such as stimulants, opioids,
      and the like, are more susceptible to develop PAH. In this review, we highlight
      the studies that support the significance of a double hit of HIV and drug abuse
      in the incidence of PAH and focus on the research that has been undertaken to
      unravel the pathobiology and vascular remodeling mechanisms underlying the
      deleterious synergy between HIV infection and drugs of abuse in orchestrating the
      development of PAH.

PMID- 30234600
TI  - The contribution of immune activation and accelerated aging in multiple myeloma
      occurring in HIV-infected population.
AB  - : The widespread use of antiretroviral treatment results in a significant
      improvement in immunological condition of people living with HIV (PLWH) who
      nevertheless experience a significantly increased risk to develop non-Hodgkin
      lymphoma compared with the general population. Despite many literature
      observations regarding multiple myeloma in PLWH, a consensus on its relevance in
      HIV infection does not exist. A number of large population studies on multiple
      myeloma in PLWH gave contrasting results, fluctuating from increased standardized
      incidence ratios to the lack of observed cases of multiple myeloma. Use of
      antiretroviral treatment, in this context, seems to induce a slight reduction of
      standardized incidence ratio, although with a partial effect, especially in young
      patients. However, a high variability in clinical onset has been described in
      different reports: the only common feature of multiple myeloma in PLWH is an
      atypical presentation as compared with general population, with a worse prognosis
      in case of uncontrolled HIV infection. We identified three pathogenetic steps in
      the complex scenario of multiple myeloma in PLWH: first, antigenic trigger;
      second, persistent T cell deficiency/dysfunction; third, altered regulation of B
      cells. All these pathogenetic steps play a role in immunological dysregulation,
      leading to B cell abnormalities and hyperactivation and, finally, resulting in
      the development of lymphoid malignancies. HIV has a role in each one of these
      three steps, due to its ability to trigger and dysregulate immune system. We
      hypothesize that HIV could be closely implicated in the multiple myeloma
      development in PLWH by accelerating the carcinogenesis events in a complex and
      only partially understood early aging process.

PMID- 30234601
TI  - Structural brain changes in perinatally HIV-infected young adolescents in South
      Africa.
AB  - OBJECTIVE: To describe the structural brain changes, neurocognitive and mental
      health associations in adolescents perinatally infected with HIV-1 infection.
      DESIGN: Cross-sectional. METHODS: Two hundred and four adolescents with
      perinatally acquired HIV and 44 uninfected frequency-matched controls aged 9-11
      years were enrolled within the Cape Town Adolescent Antiretroviral Cohort.
      Diffusion tensor imaging and structural brain MRI was done to determine
      fractional anisotropy, mean diffusivity, grey and white matter volumes, cortical
      thickness and cortical surfractional anisotropy area. Correlation coefficients
      were calculated between total grey and white matter volume, cortical surface
      area, cortical thickness, whole brain fractional anisotropy and whole brain mean
      diffusivity and clinical and laboratory parameters including general intellectual
      functioning, Becks Youth Inventory, Child Motivation Scale and Child Behaviour
      Checklist. RESULTS: HIV-infected adolescents performed worse than controls on the
      Wechsler Abbreviated Scale of Intelligence (WASI; P < 0.01). HIV-infected
      adolescents had significant fractional anisotropy decreases, mean diffusivity
      increases and decreases in cerebral grey matter volumes, cortical surface area
      and decreased gyrification. Whole-brain mean fractional anisotropy was
      significantly reduced in the HIV-infected group (P = 0.031). There were
      significant correlation coefficients between greater total grey (P = 0.008) and
      white matter volume (P = 0.004) with the WASI and the Becks self-concept subscale
      (P = 0.038). Lower whole brain fractional anisotropy was associated with higher
      scores on the Becks anger (P = 0.018) and disruptive behaviour subscales (P =
      0.031). Higher whole brain mean diffusivity was associated with apathy (P =
      0.046). CONCLUSION: The pattern of increased risk of white matter microstructure
      alterations, smaller grey matter volumes, reduced cortical surface area and
      decreased gyrification, suggests abnormal neurodevelopment in perinatally
      infected younger adolescents.

PMID- 30234599
TI  - Increased influenza-specific antibody avidity in HIV-infected women compared with
      HIV-infected men on antiretroviral therapy.
AB  - BACKGROUND: It is recommended that HIV-infected individuals receive annual
      influenza vaccination due to their high susceptibility to influenza infection,
      especially among women. However, there have been few studies investigating sex
      related responses to influenza vaccine in antiretroviral therapy (ART)-treated
      HIV-infected individuals. METHOD: In this study, 26 aviremic ART-treated HIV
      infected individuals and 16 healthy controls were enrolled in the current study.
      Blood was collected prior to vaccination (D0), on days 7-10 (D7) and on days 14
      21 (D14) following administration of the 2013-2014 seasonal influenza vaccine. A
      series of analyses evaluated the serological and cellular responses following
      influenza vaccination. RESULTS: Female HIV-infected individuals had increased
      influenza-specific antibody avidity relative to male HIV-infected individuals,
      but similar plasma levels of influenza-specific binding antibodies and
      neutralizing antibodies. Increased cycling B cells and follicular helper CD4 T
      (Tfh) cells were observed in female HIV-infected individuals pre and
      postvaccination compared with male HIV-infected individuals, and cycling Tfh
      cells were directly correlated with influenza-specific antibody avidity.
      Moreover, plasma testosterone levels were inversely correlated with antibody
      avidity index. The magnitude of microbial translocation [plasma
      lipopolysaccharide (LPS)] level was directly correlated with influenza-specific
      antibody avidity. Circulating 16S rDNA microbiome showed that enrichment of
      specific species within Proteobacteria was associated with influenza-specific
      antibody avidity. These results, including differences based on sex and
      correlations, were only observed in HIV-infected individuals but not in the
      healthy controls. CONCLUSION: This study demonstrated sex differences in
      influenza-specific antibody avidity in ART-treated HIV disease, and provides
      valuable information on vaccination strategy in the ART-treated HIV-infected
      population.

PMID- 30234602
TI  - Cost-effectiveness of preexposure prophylaxis for HIV prevention for conception
      in the United States.
AB  - OBJECTIVE: The aim of this study was to investigate the value of coformulated
      Tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) for preexposure
      prophylaxis (PrEP) for conception in the U.S. and to identify scenarios in which
      'Undetectable = Untransmittable' (U = U) may not be adequate, and rather, PrEP or
      assisted reproduction would improve outcomes. DESIGN: We developed a Markov
      cohort simulation model to estimate the incremental benefits and cost
      effectiveness of PrEP compared with alternative safer conception strategies,
      including combination antiretroviral therapy (cART) alone for the HIV-infected
      partner and assisted reproductive technologies. We modelled various scenarios in
      which HIV RNA suppression in the male partner was less than perfect. SETTING:
      U.S. healthcare sector perspective. PARTICIPANTS: Serodiscordant couples in the
      U.S. was composed of an HIV-infected male and HIV-uninfected female seeking
      conception. INTERVENTION: Economic analysis. MAIN OUTCOME MEASURE(S): Cumulative
      risks of HIV transmission to women and babies, maternal life expectancy,
      discounted quality-adjusted life years (QALY), discounted lifetime medical costs
      and incremental cost-effectiveness ratios. RESULTS: cART with condomless
      intercourse limited to ovulation was the preferred HIV prevention strategy among
      women seeking to conceive with an HIV-infected partner who is HIV-suppressed.
      PrEP was not cost-effective for women who had partners who were virologically
      suppressed. When the probability of male partner HIV suppression was low and we
      assumed generic pricing of PrEP, PrEP was cost-effective, and sometimes even cost
      saving compared with cART alone. CONCLUSION: From a U.S. healthcare sector
      perspective, when the male partner was not reliably suppressed, PrEP became
      economically attractive, and in some cases, cost-saving.

PMID- 30234603
TI  - Probable antenatal depression at antiretroviral initiation and postpartum viral
      suppression and engagement in care.
AB  - OBJECTIVE: To estimate the association of probable antenatal depression with
      postpartum HIV care engagement among pregnant women in Malawi. DESIGN: We
      conducted a prospective cohort study of 299 women who were initiating
      antiretroviral therapy (ART) through Option B+ at a government antenatal clinic
      in Malawi. METHODS: Probable antenatal depression was assessed on the day of ART
      initiation with the validated Chichewa version of the Edinburgh Postnatal
      Depression Scale (EPDS). We estimated crude and adjusted risk differences (RD,
      aRD) of visit attendance and prevalence differences (PD, aPD) of viral
      suppression through 12 months post-ART initiation comparing women with versus
      without probable antenatal depression. RESULTS: One in 10 women had probable
      antenatal depression. Most women were engaged in care through 12 months post-ART
      initiation: 85% attended all scheduled ART visits, and 81% were in care and
      virally suppressed. Women with and without probable antenatal depression had a
      comparable probability of attending all scheduled visits (RD: -0.02; 95% CI -0.16
      to 0.12; aRD: -0.04; 95% CI -0.18 to 0.10), and of viral suppression (PD: -0.02;
      95% CI -0.17 to 0.13; aPD: -0.01; 95% CI -0.17 to 0.15) in crude and adjusted
      analyses. CONCLUSION: Probable antenatal depression was not associated with
      engagement in HIV care through 12 months post-ART initiation. In a population
      with high HIV care engagement, antenatal depression may not impair HIV-related
      outcomes.

PMID- 30234604
TI  - Risk of Mycobacterium tuberculosis transmission in an antiretroviral therapy
      clinic.
AB  - OBJECTIVE: The risk of transmission of Mycobacterium tuberculosis in
      antiretroviral therapy (ART) clinics is recognized, particularly, when HIV and
      tuberculosis services are unified, but the degree of potential exposure to
      patients with infectious tuberculosis has not been measured. We aimed to quantify
      this clinic exposure. METHODS: Over 1 year, we recorded all visits to a clinic in
      northern Malawi that offers HIV testing and counselling, HIV care, ART, and TB
      diagnostic and treatment services. We included patients and guardians, noting
      timing and reason for the visit, using a palm vein reader to assist recognition
      of individuals and record times automatically. Screening for tuberculosis was
      enhanced, including induced sputum if necessary. RESULTS: Information was
      collected on 5011 individuals and 19 426 visits. During the period, 90
      individuals with bacteriologically confirmed pulmonary tuberculosis attended the
      clinic when they were likely to have been infectious (taken as 6 weeks before
      diagnosis to 2 weeks after the start of treatment), including 76 who attended
      before tuberculosis was diagnosed or suspected. We estimated that 19% of visits
      had at least 1 h of potential exposure to patients with infectious tuberculosis,
      half to patients attending prediagnosis. CONCLUSION: There was considerable risk
      of exposure, including of immunosuppressed patients, to patients with infectious
      tuberculosis, especially as repeated visits are made. Much of this exposure could
      not be avoided by separation of patients with known tuberculosis. Good
      ventilation and avoidance of crowding is essential to minimize transmission of M.
      tuberculosis in this type of setting.

PMID- 30234605
TI  - Reduced bone mineral density among HIV-infected, virologically controlled young
      men: prevalence and associated factors.
AB  - OBJECTIVE: Reduced bone mineral density (BMD) is a frequent comorbidity observed
      in people living with HIV (PLHIV). We aimed to determine the prevalence of
      reduced BMD and its associated factors among young PLHIV men, virologically
      controlled by combination antiretroviral therapy (cART). DESIGN: A bicentric
      cross-sectional study. METHODS: We selected men, aged less than 50 years, treated
      by cART, with HIV-RNA less than 50 copies/ml. BMDs of lumbar spine and hip were
      measured by dual-energy X-ray absorptiometry (DXA). A Z-score at either site
      between -1.0 and -2.0 or -2 or less defined osteopenia or osteoporosis,
      respectively. Linear and polytomous logistic regression analyses were performed.
      RESULTS: Among 230 men with a median age of 43 [interquartile range (IQR), 36-47]
      years, BMI of 23.5 (21.3-25.3) kg/m and median duration of cART of 4.2 (1.7-8.5)
      years, reduced BMD was diagnosed in 48.3%. In multivariate analyses, BMI decrease
      was associated with a risk of osteopenia [odds ratio (OR) = 1.17, P < 0.01] and
      osteoporosis (OR = 1.24, P < 0.01). Oestradiol levels decrease were associated
      with osteoporosis (OR = 1.32, P < 0.05) and lower lean mass with osteopenia (OR =
      2.98, P < 0.01). There was a protective effect of the duration of cART (OR =
      0.87, P < 0.01), which was even greater when the duration was more than 3 years
      (OR = 0.44, P = 0.02). CONCLUSION: There is a high prevalence of reduced BMD
      among young men, despite persistent virological control of HIV-infection. This
      observation raises the question of extending current recommendations for BMD
      assessment to PLHIV aged < 50 years for whom BMD has stabilized after cART
      initiation, i.e. treated for more than three years.

PMID- 30234609
TI  - We need to consider collateral damage to resistomes when we decide how frequently
      to screen for chlamydia/gonorrhoea in preexposure prophylaxis cohorts.
AB  - : Numerous preexposure prophylaxis (PrEP) guidelines recommend three-monthly
      screening for gonorrhoea and chlamydia. To quantify the risk of antimicrobial
      resistance this may induce, we conducted a literature review of the incidence of
      gonorrhoea and chlamydia in PrEP studies that conducted 3-site, 3-monthly
      screening. We found that screening could result in macrolide consumption rates
      that exceed those in high macrolide consumption populations where consumption has
      been strongly associated with macrolide resistance.

PMID- 30234608
TI  - Racial differences in human papilloma virus types amongst United States women
      with HIV and cervical precancer.
AB  - OBJECTIVE: Recent studies reported a lower human papillomavirus 16 (HPV16)
      prevalence in cervical precancer among African American than Caucasian women in
      the general population. We assessed this relationship in women with HIV. DESIGN:
      Women living with or at risk for HIV in the Women's Interagency HIV Study were
      followed semi-annually with Pap tests, colposcopy/histology (if indicated), and
      collection of cervicovaginal lavage samples for HPV testing by PCR. Racial and
      ethnic groups were defined using genomic Ancestry Informative Markers (AIMs).
      RESULTS: Among 175 cases of cervical intraepithelial neoplasia 3 or worse (CIN
      3+), 154 were diagnosed in women with HIV. African American (27%) and Hispanic
      (37%) cases were significantly less likely than Caucasian (62%) women to test
      positive for HPV16 (P = 0.01). In multivariate logistic regression models, these
      associations remained significant for African Americans (odds ratio = 0.13; 95%
      confidence interval (CI) 0.04-0.44; P = 0.001) but not Hispanics, after
      controlling for HIV status, CD4 count, history of AIDS, age, smoking, and sexual
      behavior. Limiting the analysis to women with HIV did not change the findings.
      CONCLUSION: HPV16 prevalence is lower in African American compared with Caucasian
      women with HIV and cervical precancer, independent of immune status. Future
      studies to determine why these racial differences exist are warranted, and
      whether there are similar associations between race and invasive cervical cancer
      in women with HIV. Further, HPV types not covered by quadrivalent and bivalent
      vaccines may play an especially important role in cervical precancer among HIV
      positive African American women, a possible advantage to using nonavalent HPV
      vaccine in this population.

PMID- 30234607
TI  - Interferon lambda 3/4 polymorphisms are associated with AIDS-related Kaposi's
      sarcoma.
AB  - BACKGROUND: Kaposi's sarcoma, the most common AIDS-related cancer, represents a
      major public concern in resource-limited countries. Single nucleotide
      polymorphisms within the Interferon lambda 3/4 region (IFNL3/4) determine the
      expression, function of IFNL4, and influence the clinical course of an increasing
      number of viral infections. OBJECTIVES: To analyze whether IFNL3/4 variants are
      associated with susceptibility to AIDS-related Kaposi's sarcoma among MSM
      enrolled in the Swiss HIV Cohort Study (SHCS). METHODS: The risk of developing
      Kaposi's sarcoma according to the carriage of IFNL3/4 SNPs rs8099917 and
      rs12980275 and their haplotypic combinations was assessed by using cumulative
      incidence curves and Cox regression models, accounting for relevant covariables.
      RESULTS: Kaposi's sarcoma was diagnosed in 221 of 2558 MSM Caucasian SHCS
      participants. Both rs12980275 and rs8099917 were associated with an increased
      risk of Kaposi's sarcoma (cumulative incidence 15 versus 10%, P = 0.01 and 16
      versus 10%, P = 0.009, respectively). Diplotypes predicted to produce the active
      P70 form (cumulative incidence 16 versus 10%, P = 0.01) but not the less active
      S70 (cumulative incidence 11 versus 10%, P = 0.7) form of IFNL4 were associated
      with an increased risk of Kaposi's sarcoma, compared with those predicted not to
      produce IFNL4. The associations remained significant in a multivariate Cox
      regression model after adjustment for age at infection, combination
      antiretroviral therapy, median CD4 T-cell count nadir and CD4 slopes (hazard
      ratio 1.42, 95% confidence interval 1.06-1.89, P = 0.02 for IFLN P70 versus no
      IFNL4). CONCLUSION: This study reports for the first time an association between
      IFNL3/4 polymorphisms and susceptibility to AIDS-related Kaposi's sarcoma.

PMID- 30234610
TI  - mTOR signaling mediates effects of common gamma-chain cytokines on T cell
      proliferation and exhaustion: implications for HIV-1 persistence and cure
      research.
AB  - : Chronic elevation of plasma cytokines is a key feature of HIV infection. The
      physiological consequences of this response to infection and its role in HIV
      persistence are not fully understood. Here, we show that common gamma chain
      (gammac)-cytokines induce both proliferation and expression of T cell exhaustion
      markers in a mammalian target of rapamycin (mTOR)-dependent fashion, suggesting a
      possible therapeutic target that, if inhibited, could diminish HIV reservoir
      expansion, persistence, and resistance to immune surveillance.

PMID- 30234611
TI  - Antibody-dependent cellular cytotoxicity in HIV infection.
AB  - : Interactions between the Fc segment of IgG and its receptors (FcgammaRs) found
      on cells such as natural killer cells, monocytes, macrophages and neutrophils can
      potentially mediate antiviral effects in the setting of HIV and related
      infections. We review the potential role of FcgammaR interactions in HIV, SIV and
      SHIV infections, with an emphasis on antibody-dependent cellular cytotoxicity
      (ADCC). Notably, these viruses employ various strategies, including CD4 down
      regulation and BST-2/tetherin antagonism to limit the effect of ADCC. Although
      correlative data suggest that ADCC participates in both protection and control of
      established infection, there is little direct evidence in support of either role.
      Direct evidence does, however, implicate an FcgammaR-dependent function in
      augmenting the beneficial in vivo activity of neutralizing antibodies.

PMID- 30234606
TI  - Non-Hodgkin lymphoma risk in adults living with HIV across five continents.
AB  - OBJECTIVE: To compare non-Hodgkin lymphoma (NHL) incidence rates in adults who
      started antiretroviral therapy (ART) across the Asia-Pacific, South Africa,
      Europe, Latin, and North America. METHODS: We included cohort data of adults
      living with HIV who started ART after 1995 within the framework of the
      International epidemiology Databases to Evaluate AIDS (IeDEA) and the
      Collaboration of Observational HIV Epidemiological Research in Europe (COHERE).
      We used flexible parametric survival models to compare regional NHL rates at 2
      years after ART start and to identify risk factors for NHL. RESULTS: We included
      210 898 adults with 1.1 million person-years (pys) of follow-up and 1552 incident
      NHL cases (raw overall incidence rate 142/100 000 pys). After adjusting for age
      at ART start, first-line ART regimen, calendar period of ART start, and
      especially current CD4 cell count, NHL rates were similar across regions for most
      population groups. However, South African women remained at increased risk of
      developing NHL compared with their European counterparts [adjusted hazard ratio
      [aHR] 1.79, 95% CI 1.19-2.70]. In Europe, Latin, and North America, NHL risk was
      highest in MSM (aHR 1.30, 95% CI 1.14-1.48), followed by heterosexual men
      (referent), and women (aHR 0.66, 95% CI 0.57-0.78). CONCLUSIONS: The risk of
      developing NHL is higher in women in South Africa than in Europe and higher in
      MSM compared with heterosexual men and women. Reasons for these differences
      remain unclear. Early ART access and regular patient monitoring to avert low CD4
      cell counts remain key for NHL prevention.

PMID- 30234613
TI  - Allergy Alert Test for p-Phenylenediamine-Allergic Hair Dye Users.
AB  - BACKGROUND: Contact dermatitis to hair dyes remains a health concern. Regulations
      in many countries require consumer self-testing for hair dyes, but no
      standardized procedure exists. OBJECTIVE: The aim of this study was to develop a
      self-test protocol for an allergy alert test (AAT) that can elicit a self
      noticeable alert signal in p-phenylenediamine (PPD)-allergic consumers. METHODS:
      Simulating consumer use conditions (open application for 45 minutes after mixing
      with a developer), PPD-positive hair dye-allergic subjects and PPD-negative
      control subjects were tested on the forearm and behind the ear with experimental
      products containing 0.05%, 0.25%, 0.75%, and 2% PPD. Reactions were self
      evaluated by subjects and independently assessed by dermatologists. CONCLUSIONS:
      The AAT caused a reaction self-noticeable on the forearm in 90.5% (38/42) and
      behind the ear in 93% (39/42) of the PPD-positive subjects. This was objectified
      by a dermatological evaluation. The strength of the AAT response and the number
      of responding subjects increased with increasing PPD concentrations. Allergy
      alert test responses were also dependent on the reaction strength of the
      diagnostic patch test to PPD before the study; in subjects with (+++) patch test
      reactions, 19 of 19 were positive. All 48 control subjects were negative to the
      AAT. Therefore, the AAT protocol provides a signal indicative of an allergic
      reaction in PPD-allergic hair dye consumers.

PMID- 30234614
TI  - Sleep Disturbance and Sleep-Related Impairment in Adults With Atopic Dermatitis:
      A Cross-sectional Study.
AB  - BACKGROUND: Little is known about the impact of sleep disturbances (SD) or sleep
      related impairment (SRI) in adults with AD or their relationship with severity of
      AD and itch and other predictors. OBJECTIVE: The aim of this study was to
      determine the relationship between AD severity, SD, and SRI. METHODS: We
      conducted a prospective online questionnaire-based study of 287 adults with AD,
      including assessment of AD severity by Patient-Oriented Eczema Measure, self
      reported global AD severity, Self-Assessed Eczema Area and Severity Index and
      visual analog scale-itch, Patient-Reported Outcome Measurement Information System
      SD and SRI individual items, and T scores. RESULTS: Adults with AD commonly
      endorsed all SD and SRI symptoms examined; only 58 (21.8%) reported having good
      or very good sleep quality in the past week. However, only a minority of adults
      with AD endorsed a more profound impact from these individual aspects of SD and
      SRI in the past week or Patient-Reported Outcome Measurement Information System T
      scores greater than 55. In particular, SD and SRI were associated with severe or
      very severe AD (Patient-Oriented Eczema Measure, self-reported severity, visual
      analog scale-itch, and/or Self-Assessed Eczema Area and Severity Index). Sleep
      related impairment was also associated with comorbid hay fever and/or anxiety.
      CONCLUSIONS: This study suggests that SD and SRI are common in adults with AD,
      particularly those with severe diseases. Sleep disturbances and SRI should be
      considered when assessing burden of AD and therapeutic decisions.

PMID- 30234615
TI  - What Is Tetrasodium Etidronate and How Is It Related to Formaldehyde?

PMID- 30234616
TI  - Clostridium butyricum MIYAIRI 588 as Adjunctive Therapy for Treatment-Resistant
      Major Depressive Disorder: A Prospective Open-Label Trial.
AB  - AIM: Up to 60% of depressed patients do not obtain sufficient relief from a
      course of antidepressant therapy, and these treatment-resistant major depressive
      disorder (TRD) patients are at increased risk for relapse, chronicity, persistent
      psychosocial impairments, and suicide. Probiotics actively participate in
      treatment of neuropsychiatric disorders. However, the role of gut microbiota in
      brain disorders and depression remains unclear. We performed a prospective study
      to evaluate the effects of Clostridium butyricum MIYAIRI 588 (CBM588). METHODS:
      This was an 8-week open-label study to evaluate the efficacy and safety of CBM588
      in combination with antidepressants in adult patients diagnosed with TRD
      according to Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, Text Revision. Forty antidepressant-treated inpatients were included.
      Patients were randomized to adjuvant treatment with CBM588 (n = 20) or control (n
      = 20). The primary endpoint was the change in the 17-item Hamilton Depression
      Rating Scale score from baseline to week 8. Secondary end points were changes in
      the Beck Depression Inventory and the Beck Anxiety Inventory scale scores from
      baseline to week 8. The Systematic Assessment of Treatment Emergent Events
      General Inquiry was used to assess adverse effects. RESULTS: CBM588 (60 mg/d) in
      combination with antidepressants (flvoxamine, paroxetine, escitalopram,
      duroxetine, and sertraline) provided significant improvement in depression. All
      patients completed the trial, and 70% responded to treatment; the remission rate
      was 35.0%. No serious adverse events occurred. CONCLUSIONS: These preliminary
      data suggest that CBM588 in combination with antidepressants is effective and
      well tolerated in the treatment of TRD. Further studies using a larger, double
      blind, parallel-group design are warranted to confirm these findings.

PMID- 30234618
TI  - An Analysis of the Influence of Physical Activity Level on Total Knee
      Arthroplasty Expectations, Satisfaction, and Outcomes: Increased Revision in
      Active Patients at Five to Ten Years.
AB  - : This article was updated on September 19, 2018, because of a previous error. On
      page 1546, in the section titled "Discussion," the sentence that had read
      "Although a significant improvement was found in the vast majority of the
      inactive group, surprisingly, a majority of the active group (72.7%) reported a
      decrease in their activity levels below their baseline at 5 to 10 years
      postoperatively." now reads "Although a significant improvement was found in the
      vast majority of the inactive group, surprisingly, a majority of the active group
      (72.7%) reported no change or a decrease in their activity levels below their
      baseline at 5 to 10 years postoperatively." BACKGROUND: Patients undergoing total
      knee arthroplasty expect pain relief, functional improvement, and a return to
      physical activity. The objective of this study was to determine the impact of
      patients' baseline physical activity level on preoperative expectations,
      postoperative satisfaction, and clinical outcomes in patients undergoing total
      knee arthroplasty. METHODS: Using an institutional registry from 2007 to 2012, we
      retrospectively identified patients who underwent a unilateral primary total knee
      arthroplasty for osteoarthritis and completed a preoperative Lower Extremity
      Activity Scale (LEAS), a Hospital for Special Surgery Knee Replacement
      Expectations Survey (HSS-KRES), and a Knee injury and Osteoarthritis Outcome
      Score (KOOS) evaluation in addition to 2-year KOOS and satisfaction evaluations.
      Active patients were defined by an LEAS level of 13 to 18. Active patients (n =
      1,008) were matched to inactive patients (n = 1,008) by age, sex, body mass
      index, and comorbidities. The cohorts were compared with regard to the
      association of expectations with KOOS and satisfaction, the change in LEAS level
      from baseline to 2 years, complications, and revision surgical procedures.
      Multivariable analyses identified predictors of satisfaction, KOOS, and revision
      surgical procedures. RESULTS: Significantly more active patients (68.2%) expected
      to be back to normal with regard to the ability to exercise and participate in
      sports compared with inactive patients (55.5%; p < 0.0001). Although overall
      satisfaction was equivalent, active patients were more commonly very satisfied
      with regard to the ability to do recreational activities (67.2% compared with
      57.7%; p = 0.001). There were no associations between expectations and
      satisfaction or outcomes. Only the inactive patient group improved in activity
      level at 2 years. At 2 years, 69.5% of the inactive patients and 27.3% of the
      active patients improved upon their baseline activity levels (p < 0.0001).
      Complications rates were similar. The revision rate was higher for active
      patients (3.2%) compared with inactive patients (1.6%) at 5 to 10 years
      postoperatively (p = 0.019). CONCLUSIONS: At 2 years following total knee
      arthroplasty, inactive patients improved from baseline activity levels and active
      patients did not. Active patients had an elevated revision risk. Therefore,
      active patients should be carefully counseled regarding total knee arthroplasty
      to give them an understanding of its limitations and the potential risk of future
      revision. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 30234619
TI  - The Impact of Electronic Medical Record Implementation on Labor Cost and
      Productivity at an Outpatient Orthopaedic Clinic.
AB  - BACKGROUND: Widespread adoption of electronic medical record (EMR) systems is
      increasing. EMR implementation can be costly and typically requires workflow
      redesign. To our knowledge, no studies to date have examined the impact of EMR
      implementation using advanced cost accounting methods or the impact of its
      implementation on orthopaedic surgeons in an outpatient setting. METHODS: Time
      driven activity-based costing (TD-ABC) was used to evaluate the effect of EMR
      implementation in an outpatient adult reconstruction clinic. One hundred and
      forty-three patients were prospectively timed throughout their visit to clinics,
      before implementation of a hospital system-wide EMR system and then again 2
      months, 6 months, and 2 years after implementation. Data were analyzed to
      investigate the effects of EMR implementation on labor cost and provider time.
      RESULTS: Total labor costs per patient visit significantly increased at 2 months
      after EMR implementation (from $36.88 to $46.04; p = 0.05). Drivers of this
      change included increases in the amount of time that attending surgeons spent per
      patient (from 9.38 to 10.97 minutes, with the cost increasing from $21.10 to
      $27.01), as well as increased time that certified medical assistants spent
      assessing patients (from 3.4 to 9.1 minutes; p < 0.001). Two months after EMR
      implementation, providers were spending more than twice as long documenting
      patient encounters (7.6 compared with 3.3 minutes; p < 0.001). However, by 6
      months after implementation, total labor costs were similar to those before
      implementation ($38.75 compared with $36.88; p = 0.689) and they remained similar
      at 2 years after implementation ($36.88 compared with $37.73; p = 0.84). After
      the initial learning period following EMR implementation, providers spent more
      time documenting encounters (8.43 compared with 3.28 minutes; p < 0.001) but less
      time interacting with patients (10.03 compared with 14.65 minutes; p = 0.013).
      CONCLUSIONS: Using TD-ABC, we observed the EMR implementation learning period,
      returning to pre-introduction efficiency at 6 months. Cost increases because of
      increased certified medical assistant time spent with patients and physician time
      on documentation were offset by less patient-physician interaction. Health-care
      systems and policymakers should be aware that the length of the implementation
      period is approximately 6 months and that implementation may alter the time that
      providers spend with patients. CLINICAL RELEVANCE: This article offers insight
      into the impact of EMR implementation on the orthopaedic surgeon's clinic
      efficiency and workflows.

PMID- 30234617
TI  - Movement Disorders After Exposure to Antipsychotic Drugs in Patients With
      Depressive Disorders.
AB  - OBJECTIVES: The aims of the study were to explore the frequency of movement
      disorders (MDs) in depressive patients exposed to antipsychotic drugs (APDs) and
      to compare it with nonexposed depressive patients and APDs-treated schizophrenic
      patients. METHODS: Four hundred fifty-two depressive patients not exposed to APDs
      (group A), 156 depressives exposed to APDs (group B), and 75 patients with
      schizophrenia on APDs (group C) were recruited. Presence of MDs was explored by
      the Simpson-Angus and UKU scales (Registration: NCT02409823). RESULTS: Movement
      disorders were observed in 5%, 9%, and 13% of patients in groups A to C,
      respectively (P < 0.001, chi for linear trend). A logistic multivariate analysis
      revealed that male sex (odds ratio = 2.26, 95% confidence interval = 1.13-4.49, P
      < 0.01), exposure to first-generation (vs second-generation) APDs (odds ratio =
      5.71, 95% confidence interval = 2.08-15.66, P < 0.01), and exposure to lithium
      (odds ratio = 3.99, 95% confidence interval = 1.74-9.14, P < 0.01) were
      independently and significantly associated with MDs. CONCLUSIONS: Male sex, use
      first-generation APDs, and exposure to lithium were associated with MDs in
      depression. Therefore, caution is advised with the use of these drugs in
      depressive patients. Prospective studies are needed to confirm these results.

PMID- 30234620
TI  - Assessment of Ankle Mortise Instability After Isolated Supination-External
      Rotation Lateral Malleolar Fractures.
AB  - BACKGROUND: The diagnosis of clinically important instability following isolated
      supination-external rotation (SER) distal fibular fractures is a challenge. The
      purpose of this study was to investigate the accuracy of clinical findings
      including medial tenderness, swelling, and ecchymosis, combined with the gravity
      stress test and magnetic resonance imaging (MRI), in the assessment of ankle
      mortise stability in association with isolated SER-type lateral malleolar
      fractures. The external rotation (ER) stress test was used as the reference with
      which the methods of assessment were compared. METHODS: Thirty-seven patients
      were enrolled prospectively. Using the ER stress test as a reference, we
      evaluated the sensitivity, specificity, likelihood ratio (LR), and post-test
      probability of instability when using clinical examination, the gravity stress
      test, and MRI for diagnosing ankle mortise instability after an isolated SER
      lateral malleolar fracture. RESULTS: The positive LR for clinical findings ranged
      from 1.45 to 2.54, and the negative LR ranged from 0.25 to 0.70, shifting the pre
      test probability to a rarely important degree. In contrast, the positive LR for
      the gravity stress test was 5.71 with a 95% confidence interval (CI) of 1.52 to
      21.48, a moderate shift from the pre-test probability, and the negative LR was
      0.33 (95% CI = 0.16 to 0.66), indicating a small shift. In cases with a deep
      deltoid ligament disruption identified on MRI, the positive LR was 3.05 (95% CI =
      1.03 to 9.02) and the negative LR was 0.53 (95% CI = 0.31 to 0.91), demonstrating
      a small but sometimes important shift. CONCLUSIONS: The gravity stress test is a
      reliable method for diagnosing ankle mortise instability in patients with an
      isolated SER lateral malleolar fracture. Nevertheless, this test alone would not
      qualify as a replacement for the ER stress test. However, when the gravity stress
      test result is consistent with the clinical or MRI findings, its diagnostic value
      is almost equivalent to that of the ER stress test. LEVEL OF EVIDENCE: Diagnostic
      Level II. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30234621
TI  - A Dedicated Pediatric Spine Deformity Team Significantly Reduces Surgical Time
      and Cost.
AB  - BACKGROUND: As high-quality health care becomes increasingly expensive,
      improvement projects are focused on reducing cost and increasing value. To
      increase value by reducing operating room (OR) utilization, we studied the effect
      of a dedicated team approach for posterior spinal fusion (PSF) for scoliosis.
      METHODS: With institutional support, an interdisciplinary, dedicated team was
      assembled. Members developed standardized protocols for anesthetic management and
      patient transport, positioning, preparation, draping, imaging, and wake-up. These
      protocols were initially implemented with a small interdisciplinary team,
      including 1 surgeon (Phase 1), and then were expanded to include a second surgeon
      and additional anesthesiology staff (Phase 2). We compared procedures performed
      with a dedicated team (the Dedicated Team cases) and procedures performed without
      a such a team (the Casual Team cases). Because of the heterogeneous nature of PSF
      for scoliosis, we developed a case categorization system: Category 1 was
      relatively homogeneous and indicated patients with fusion of <=12 levels, no
      osteotomies, and a body mass index (BMI) of <25 kg/m, and Category 2 was more
      heterogeneous and indicated patients with fusion of >12 levels and/or >=1
      osteotomy and/or a BMI of >=25 kg/m. RESULTS: In total, 89 Casual Team and 78
      Dedicated Team cases were evaluated: 71 were in Category 1 and 96 were in
      Category 2. Dedicated Team cases used significantly less OR time for both
      Categories 1 and 2 (p < 0.001). In Category-1 cases, the average reduction was
      111.4 minutes (29.7%); in Category-2 cases, it was 76.9 minutes (18.5%). The
      effect of the Dedicated Team was scalable: the reduction in OR time was
      significant in both Phase 1 and Phase 2 (p < 0.001). The Dedicated Team cases had
      no complications. Cost reduction averaged approximately $8,900 for Category-1 and
      $6,000 for Category-2 cases. CONCLUSIONS: By creating a dedicated team and
      standardizing several aspects of PSFs for scoliosis, we achieved a large
      reduction in OR time. This increase in team efficiency was significant,
      consistent, and scalable. As a result, we can routinely complete 2 Category-1
      PSFs in the same OR with the same team without exceeding standard block time.

PMID- 30234622
TI  - The Demographic and Geographic Trends of Meniscal Procedures in New York State:
      An Analysis of 649,470 Patients Over 13 years.
AB  - BACKGROUND: The purpose of this study was to examine the geographic and
      demographic variations and time trends of different types of meniscal procedures
      in New York State to determine whether disparities exist in access to treatment.
      METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS)
      outpatient database was reviewed to identify patients who underwent elective,
      primary knee arthroscopy between January 1, 2003, and December 31, 2015, for 1 of
      the following diagnosis-related categories: Group 1, meniscectomy; Group 2,
      meniscal repair; and Group 3, meniscal allograft transplantation, with or without
      anterior cruciate ligament reconstruction (ACLR). The 3 groups of meniscal
      procedures were compared on geographic distribution, patient age, insurance,
      concomitant ACLR, and surgeon and hospital volume over the study period. RESULTS:
      A total of 649,470 patients who underwent knee arthroscopy between 2003 and 2015
      were identified for analysis. Both meniscectomies and meniscal repairs had a
      scattered distribution throughout New York State, with allograft volume
      concentrated at urban academic hospitals. The majority of patients who underwent
      any meniscal procedure had private insurance, with Medicaid patients having the
      lowest rates of meniscal surgery. At high-volume hospitals, meniscal repairs and
      allografts are being performed with increasing frequency, especially in patients
      <25 years of age. Meniscal repairs are being performed concomitantly with ACLR
      with increasing frequency. CONCLUSIONS: Meniscal repairs and allografts are being
      performed at high-volume hospitals for privately insured patients with increasing
      frequency. Geographic access to these treatments, particularly allografts, is
      limited. CLINICAL RELEVANCE: Disparities in the availability of advanced meniscal
      treatment require further investigation and understanding to improve access to
      care.

PMID- 30234623
TI  - Botulinum Toxin Type A Versus Placebo for Idiopathic Clubfoot: A Two-Center,
      Double-Blind, Randomized Controlled Trial.
AB  - BACKGROUND: Congenital idiopathic clubfoot is a condition that affects, on
      average, approximately 1 in 1,000 infants. One broadly adopted method of
      management, described by Ponseti, is the performance of a percutaneous complete
      tenotomy when hindfoot stall occurs. The use of onabotulinum toxin A (BTX-A)
      along with the manipulation and cast protocol described by Ponseti has been
      previously reported. Our goal was to compare the clinical outcomes between BTX-A
      and placebo injections into the gastrocnemius-soleus muscle at the time of
      hindfoot stall in infants with idiopathic clubfoot treated with the Ponseti
      method of manipulation and cast changes. METHODS: This was a double-blind,
      placebo-controlled, parallel-group study with balanced randomization. RESULTS: At
      6 weeks after the study injection (T1), 66% of the 32 feet in the BTX-A arm and
      63% of the 30 in the placebo arm responded to the treatment (i.e., obtained >=15
      degrees  of dorsiflexion). Seven of the 11 patients in the BTX-A arm and all of
      the 11 in the placebo arm who had not responded at T1 responded to a rescue BTX-A
      injection at 12 weeks after the first injection (T2). The combined response rate
      at T2, which included the first-time responders as well as the patients who did
      not respond at T1 but did at T2, was 88% in the BTX-A arm and 100% in the placebo
      arm, culminating in a 94% response rate at T2. At T3 (2 years of age), 89% of the
      feet continued to respond and there was an 8% surgical rate. CONCLUSIONS: There
      was no difference in outcomes between the BTX-A and placebo groups when the
      injection was performed at the time of hindfoot stall. Overall, 92% of the
      clubfeet in this study responded to a manipulation and cast protocol alone, with
      or without BTX-A injection, by 12 weeks after hindfoot stall, or we can say that
      92% of the clubfeet did not require percutaneous Achilles tendon lengthening by 2
      years of age. The need for tenotomy is limited to those who have not responded to
      treatment at this point, and the need for surgery is limited to those for whom
      all attempts at treatment with sequential casts, BTX-A, and percutaneous Achilles
      tendon lengthening have failed. LEVEL OF EVIDENCE: Therapeutic Level I. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30234624
TI  - Staggered Rather Than Staged or Simultaneous Surgical Strategy May Reduce the
      Risk of Acute Kidney Injury in Patients Undergoing Bilateral TKA.
AB  - BACKGROUND: The strategy for bilateral total knee arthroplasty (TKA) depends on
      the timing of surgery for each knee. The purpose of this study was to determine
      whether the type of surgical strategy for bilateral TKA (staggered, staged, or
      simultaneous) influences the incidence of acute kidney injury (AKI) and related
      complications. METHODS: Enrolled patients from a single tertiary teaching
      hospital were divided into 3 groups according to the surgical strategy for
      bilateral TKA: staggered (<=7 days between the first and second procedure; n =
      368), staged (8 days to 1 year between the first and second procedure; n = 265),
      or simultaneous (n = 820). The incidence of AKI as defined by the Kidney Disease
      Improving Global Outcomes (KDIGO) criteria was assessed. The rates of major
      postoperative complications, major adverse cardiovascular and cerebral events,
      intensive care unit (ICU) admissions, and mortality were also evaluated. To
      reduce the influence of possible confounding factors, inverse probability of
      treatment weighting based on propensity-score analysis was used. RESULTS: The
      primary outcome was the incidence of AKI according to surgical strategy. The
      staggered group had a lower rate of AKI compared with the other 2 groups (p <
      0.001): 2.4% (9 of 368 patients), 6.0% (16 of 265), and 11.2% (92 of 820) in the
      staggered, staged, and simultaneous groups, respectively. CONCLUSIONS: The type
      of bilateral TKA strategy was an independent risk factor for the development of
      AKI. The assessment of additional risk factors for the development of AKI is
      essential before deciding on surgical strategy. LEVEL OF EVIDENCE: Therapeutic
      Level III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 30234626
TI  - Unfavorable Outcomes Following Surgical Treatment of Hallux Valgus Deformity: A
      Systematic Literature Review.
AB  - BACKGROUND: Surgical correction of deformity plays a central role in the
      treatment of hallux valgus deformity. However, complications or unintended
      outcomes are frequently noted in clinical series. There has been no rigorous
      systematic review of studies reporting outcomes of surgical treatment for hallux
      valgus deformity, to the best of our knowledge. METHODS: We performed a
      systematic review of studies reporting the outcomes of surgical correction for
      hallux valgus deformity. RESULTS: A total of 229 studies met the inclusion
      criteria. The pooled rates of postoperative patient dissatisfaction and
      postoperative first metatarsophalangeal pain were 10.6% and 1.5%, respectively.
      The overall rate of recurrent deformity was 4.9%. CONCLUSIONS: Hallux valgus
      surgery has been reported to have fairly consistent results and rates of
      complications or unfavorable outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 30234625
TI  - Local Versus Systemic Antibiotics for Surgical Infection Prophylaxis in a Rat
      Model.
AB  - BACKGROUND: The purpose of this study was to compare the local application of a
      variety of antimicrobial agents with intravenous (IV) antibiotics for infection
      prophylaxis in a rat model. METHODS: A total of 120 adult male Sprague-Dawley
      rats were implanted with an expanded polytetrafluoroethylene (ePTFE) vascular
      graft in a submuscular position and challenged with 2 * 10 colony-forming units
      of methicillin-sensitive Staphylococcus aureus (MSSA). Twenty rats received
      pretreatment with IV cefazolin and 20 rats were pretreated with IV vancomycin.
      The remaining 80 rats had application of local antimicrobials in the wound at the
      conclusion of the procedure: 20 rats received vancomycin powder; 20 rats,
      cefazolin powder; and 20 rats, tobramycin powder; 20 rats underwent dilute 0.35%
      Betadine (povidone-iodine) lavage for 3 minutes. One week after surgery, the
      grafts were retrieved and cultured. RESULTS: Twenty (100%) of 20 rats in each of
      the IV cefazolin, IV vancomycin, and dilute Betadine lavage groups had grossly
      positive cultures for MSSA (95% confidence interval [CI], 84% to 100%). Eighteen
      (90%) of 20 rats in the cefazolin local powder group demonstrated positive
      cultures for MSSA (95% CI, 77% to 100%). Four (20%) of 20 rats in the tobramycin
      local powder and vancomycin local powder groups demonstrated positive cultures
      for MSSA (95% CI, 3% to 38%). The infection rates for the local application of
      vancomycin and tobramycin powder were significantly lower compared with Betadine
      lavage, IV vancomycin, IV cefazolin, and local cefazolin powder (p < 0.000001).
      CONCLUSIONS: Local antimicrobial prophylaxis with vancomycin and tobramycin
      powder for infections in the rat model was statistically superior to systemic
      prophylaxis with IV antibiotics, local cefazolin powder, and Betadine lavage.
      CLINICAL RELEVANCE: This study supports the findings of prior clinical reports
      that intrawound vancomycin powder reduces the risk of surgical site infection.
      Local application of tobramycin powder was equivalent to vancomycin powder in
      this model. Additionally, the superiority of local antibiotic surgical
      prophylaxis suggests that clinical studies should be considered to determine the
      relative efficacy of local versus systemic antibiotics for surgical infection
      prophylaxis in humans.

PMID- 30234627
TI  - Spine-Pelvis-Hip Relationship in the Functioning of a Total Hip Replacement.

PMID- 30234628
TI  - What's New in Hip Replacement.

PMID- 30234629
TI  - Update on Misrepresentation of Research Publications Among Orthopaedic Surgery
      Residency Applicants.
AB  - BACKGROUND: Our 2 previous studies (1999, 2007) examining misrepresentation of
      research publications among orthopaedic residency applicants revealed rates of
      misrepresentation of 18.0% and 20.6%, respectively. As the residency selection
      process has become more competitive, the number of applicants who list
      publications has increased. The purpose of this study was to determine current
      rates of research misrepresentation by orthopaedic surgery applicants. METHODS:
      We reviewed the publication listings and research section of the Common
      Application Form from the Electronic Residency Application Service (ERAS) for all
      applicants applying to 1 orthopaedic residency program. The PubMed-MEDLINE
      database was principally used to search for citations. The PubMed Identifier
      (PMID) number was used; if no PMID number was listed, a combination of authors or
      the title of the work was used. If the citations were not found through PubMed, a
      previously developed algorithm was followed to determine misrepresentation.
      Misrepresentation was defined as (1) nonauthorship of a published article in
      which authorship was claimed, (2) claimed authorship of a nonexistent article, or
      (3) self-promotion to a higher authorship status within a published article.
      RESULTS: Five hundred and seventy-three applicants applied to our institution for
      residency in 2016 to 2017: 250 (43.6%) of 573 applicants did not list a
      publication, whereas 323 (56.4%) of 573 applicants listed >=1 publication. We
      found 13 cases of misrepresentation among a total of 1,100 citations (1.18% in
      2017 versus 18.0% in 1999 and 20.6% in 2007, p < 0.001). Ten cases of
      misrepresentation were self-promotion to a higher authorship status. There were 2
      cases of claimed authorship of an article that could not be found. Only 1
      applicant misrepresented more than once. CONCLUSIONS: Based on our findings,
      orthopaedic surgery residency applicants are accurately representing their
      publication information. The incorporation of the PMID number on the ERAS
      application has streamlined the process for finding publications, and has
      possibly encouraged veracity on residency applications. Faculty involved in the
      resident selection process should be aware of the significant decline in the rate
      of misrepresentation by medical students applying for orthopaedic surgery
      residency versus the rate in our prior studies.

PMID- 30234631
TI  - Managing Expectations: The Bigger They Are, the Harder They Fall: Commentary on
      an article by Danielle Y. Ponzio, MD, et al.: "An Analysis of the Influence of
      Physical Activity Level on Total Knee Arthroplasty Expectations, Satisfaction,
      and Outcomes. Increased Revision in Active Patients at Five to Ten Years".

PMID- 30234630
TI  - Progressive Autonomy in the Era of Increased Supervision: AOA Critical Issues.
AB  - The observation of decreased resident autonomy, ultimately influencing the
      readiness of a new graduate to practice, has been supported with a number of
      recent surveys. This perceived lack of autonomy is felt to be due, in part, to
      many reasons, including duty-hour regulations, increased supervision
      requirements, patient safety measures, concern for complication rates, and other
      performance measures. Pressure on faculty members to have increased clinical
      productivity may not allow for more resident autonomy.Increased clinical exposure
      to improve resident independence may come from several suggested areas. First,
      restructuring the residency program to allow for more clinical time may be one
      way to improve education. Second, increased use of surgical simulation will allow
      for more experience to develop technical skills within a controlled environment.
      Surgical simulators can be used to acquire new skills and also as a means of
      assessing competence. Third, competency-based education (CBE) has been offered as
      a way to improve resident education. At its core, CBE offers criterion-based
      assessments for residents and faculty that allow for more frequent feedback.

PMID- 30234632
TI  - Hallux Valgus Correction: The Best Technique Is Still Up for Debate: Commentary
      on an article by Alexej Barg, MD, et al.: "Unfavorable Outcomes Following
      Surgical Treatment of Hallux Valgus Deformity. A Systematic Literature Review".

PMID- 30234633
TI  - Needle or Knife at Hindfoot Stall?: Commentary on an article by Christine M.
      Alvarez, MD, FRCSC, MSc, et al.: "Botulinum Toxin Type A Versus Placebo for
      Idiopathic Clubfoot. A Two-Center, Double-Blind, Randomized Controlled Trial".

PMID- 30234634
TI  - Resource Dependency and Hospital Performance in Hospital Value-Based Purchasing.
AB  - To help influence the health care environment as well as the flow of resources
      into and out of hospitals, the Centers for Medicare & Medicaid Services has
      implemented a performance incentive initiative called the Hospital Value-Based
      Purchasing (HVBP) program. As such, this study utilizes the lens of Resource
      Dependency Theory to evaluate the effect of the external environment on hospital
      performance as measured by the HVBP program. This study utilizes data from the
      2014 American Hospital Association (AHA) Annual Survey database, 2014 Area Health
      Resource File (AHRF), the 2014 Medicare Final Rule Standardizing File, and the
      2014 Medicare Hospital Compare database. The associations between external
      environment and hospital performance are assessed through multiple regression
      analysis. Hospital performance scores in the HVBP program are sensitive to
      environmental factors; however, not all domains are influenced to the same
      degree. It would seem that hospitals do not have either the same ability or
      motivation to make changes in each of the value-based purchasing domains.
      Ultimately, the findings from this study indicate that environmental forces do
      play a role in hospitals' performance in the HVBP program.

PMID- 30234635
TI  - The Effects of Implementing an Accreditation Process on Health Care Quality Using
      Structural Equation Modeling.
AB  - This study was undertaken to investigate nurses' perceptions of and attitudes
      toward the effects of hospital accreditation on their service quality in an eye
      hospital in Tehran in 2016. This was a cross-sectional and descriptive-analytic
      study conducted in the second half of 2016. Data of 200 nurses who were selected
      using a census method were studied. For collecting the required data, a standard
      questionnaire was used. Data were analyzed using SPSS 21.0 through descriptive
      statistics, as well as AMOS 18.0 software through the measurement and structural
      models of structural equation modeling method. The results showed that the
      independent variables of nurses' participation and the benefits of accreditation
      had predicted 63% of the variations in the dependent variable of "quality." Also,
      the results of structural equation modeling showed that the benefits of
      accreditation (regression weight = 0.22) had a significant effect on quality
      outcomes (P = .02). Moreover, the participation of nurses (regression weight =
      0.61) had an important effect on quality outcomes (P < .001). Finally, the
      benefits of accreditation had a significant association with the nurses'
      participation (regression weight = 0.50) (P < .001). According to the results of
      the present study, the hospital accreditation program had positive effects on the
      quality of care from the studied nurses' perspective.

PMID- 30234636
TI  - The Nationwide Health Information Network: The Case of the Expansion of Health
      Information Exchanges in the United States.
AB  - The Nationwide Health Information Network (NHIN) implemented secure exchange of
      health records through utilization of the Internet. The NHIN has greatly assisted
      in achieving the goals of the Health Information Technology for Economic and
      Clinical Health Act by promoting the adoption of Meaningful Use. Epic introduced
      a Health Information Exchange platform, Care Everywhere, which has facilitated
      Health Information Exchange availability. The purpose of this research was to
      determine the impact of NHIN and Epic Care's Care Everywhere on health care to
      determine whether their use in the emergency department (ED) has increased. The
      methodology for this study utilized a literature review. Twenty-eight sources
      were referenced for this study. With the NHIN implementation, repeated visits
      were decreased, visit times became faster, and charges were lower. Emergency
      department reported significant benefits with sharing clinical information. The
      NHIN implementation throughout the ED has increased the quality of health care;
      duplicated tests and drug usage were determined, and a reduction of the ED length
      of stay was also achieved.

PMID- 30234637
TI  - Wolcott-Rallison Syndrome With Different Clinical Presentations and Genetic
      Patterns in 2 Infants.
AB  - Wolcott-Rallison syndrome is a rare disease presenting with insulin-dependent
      diabetes mellitus (DM) before 6 months old, skeletal dysplasia after 6 months
      old, and liver failure. Other manifestations are renal failure, microcephaly,
      epilepsy, central hypothyroidism, neutropenia, and dental and dermal problems.
      The cases were 2 patients from 2 different states of Iran (Khoozestan and Fars)
      who had developed DM before 6 months old. The first one was a 7-month-old infant
      who was healthy; in the genetic study (screening), autosomal recessive pattern
      and novel deletion in EIF2AK3 were reported; her sister had died at 5.5 years old
      due to diabetic ketoacidosis (DKA) that was associated with liver and renal
      failure. The second patient had developed DKA at 45 days old, which was
      associated with mild acute tubular necrosis and abnormal coagulation tests at
      onset clinical presentation, which were then resolved. He was treated with
      insulin, and at follow-up, the laboratory data are normal; in the genetic study,
      EIF2AK3 nonsense homozygous mutation was diagnosed. Genetic study of patients
      with insulin-dependent DM before 6 months old, especially those with DKA and
      associated with or without other disorders; attention to novel deletion of in
      EIF2AK3 gene; screening for skeletal dysplasia after 1 year old; and renal,
      liver, pancreatic, and thyroid function tests are recommended.

PMID- 30234638
TI  - Social Capital, Community Capacity, and Health.
AB  - The capacity to practice health behavior is different for each individual.
      Community capacity and social capital deal with understanding the relationship
      between community members and with the factors that promote or delay collective
      activities. This study examines existing literature in relation to social
      capital, health, and community capacity. Bonding social capital shows the average
      value of the extent to which individuals trust each other and participate in
      groups, whereas bridging social capital shows the average value of the extent to
      which individuals participate in different formal groups. Community capacity
      seeks mutual cooperation based on trust, and cohesion minimizes community
      problems, and it has become evident that such capacity is a useful tool for
      health improvement.

PMID- 30234639
TI  - The Lived Experience of First-Year Nurses at Work.
AB  - The aim of this qualitative phenomenological research study was to gain insight
      on the lived experiences of newly licensed nurses. First-year nurses describe
      poor experiences and struggle in their first year of practice, leading to high
      turnover and burnout. In-depth interviews were conducted with 12 newly licensed
      registered nurses. Major themes identified were (1) the impact of nursing school,
      (2) hospital orientation of a new nurse, (3) environment that promotes teamwork,
      (4) taking time for self-care, (5) confidence, and (6) expectations versus
      reality in doctor interactions. In conclusion, understanding the lived
      experiences of a new nurse gives insight to current nursing students, including
      expectations and tips for succeeding in the first year of practice. Current
      orientation programs in northern Indiana were found to adequately prepare new
      graduates for professional practice.

PMID- 30234640
TI  - Case Study of Nurses' Experiences Related to the Deaths of Their Patients.
AB  - A qualitative case study methodology was applied to explore how nurses cope when
      their patients die. The study utilized a sample of 16 participants at a rural 123
      bed community hospital. Nine themes regarding nurses dealing with grief emerged:
      (a) family issues, (b) patient alone at death, (c) knowing the community, (d)
      never-forgotten experiences, (e) first experiences, (f) time issues, (g)
      responses to unexpected deaths, (h) role of nurses, and (i) nurses' response to
      death itself. It is concluded that nurses need to grieve. If nurses do not know
      how to cope with deaths of their patients, it may lead to personal health issues.
      There is a need for further research to evaluate whether improved end-of-life
      education and counseling address the needs of the nurses who deal with deaths of
      their patients. Globally, nurses cope with death and need to grieve when their
      patients die. Knowledge introduced from this research adds to the knowledge of
      the skills and coping of nurses everywhere.

PMID- 30234641
TI  - Interpersonal Competence in the Management of People.
AB  - Interpersonal skills are those essential skills applied in dealing with and
      relating to other people largely on a one-to-one basis. The interpersonal
      communication behavior of many people suggests they assume an ability to
      communicate effectively that they do not possess, taking these skills for
      granted. One must work conscientiously to develop interpersonal competence by
      doing the rights things at all times and doing them repeatedly until they become
      ingrained. As with any human skills, interpersonal skills can be improved through
      conscious effort. Successful interpersonal communication involves shaping the
      behavior of others often while countering their shaping behavior. To have a
      chance of being successful, every interpersonal contact must have an objective,
      and every effort must be made to avoid creating win-lose transactions whenever
      possible.

PMID- 30234642
TI  - Factors and Preferences in Patient Selection and Location of Care.
AB  - There are many factors that influence the decisions that patients make regarding
      where they receive care. Two hundred thirty-three patients were surveyed in the
      primary care setting to determine patient satisfaction and characteristics that
      led patients to seeking treatment at primary care offices, urgent care centers,
      or emergency rooms. Respondents rated quality of care highest at the primary care
      office (P < .001). Patients also demonstrated preference for in-person care
      compared with video conferencing or telephone visits (P < .001).

PMID- 30234643
TI  - LI-RADS: a great opportunity not to be missed.
AB  - The Liver Imaging Reporting and Data System (LI-RADS) is a widespread
      comprehensive system for standardising the reporting and data collection of liver
      imaging to standardise chronic liver disease evaluation. However, the LI-RADS,
      based on the identification of some categories of lesions by means of a
      conceptual and nonquantitative probability approach, has many limitations. In
      fact, recently, the European Association for the Study of the Liver Guidelines
      regarding the management of hepatocellular carcinoma did not accept the LI-RADS.
      The aim of this paper was to critically analyse the LI-RADS, focusing on some
      interesting issues such as the absence of a clear distinction between two
      different imaging modalities (computed tomography and MRI), the lack of
      validation of some major features, the assessment of its ancillary features and
      its complexity. Despite these limitations, the LI-RADS represents a great
      opportunity for the radiological community. We must not let it escape, but time
      and experience are necessary for its improvement.

PMID- 30234644
TI  - Marijuana is not associated with progression of hepatic fibrosis in liver
      disease: a systematic review and meta-analysis.
AB  - BACKGROUND: An estimated 22 million adults use marijuana in the USA. The role of
      marijuana in the progression of hepatic fibrosis remains unclear. AIMS: We
      carried out a systematic review and meta-analysis to evaluate the impact of
      marijuana on prevalence and progression of hepatic fibrosis in chronic liver
      disease. PATIENTS AND METHODS: We searched several databases from inception
      through 10 November 2017 to identify studies evaluating the role of marijuana in
      chronic liver disease. Our main outcome of interest was prevalence/progression of
      hepatic fibrosis. Adjusted odds ratios (ORs) and hazards ratios (HRs) were pooled
      and analyzed using random-effects model. RESULTS: Nine studies with 5 976 026
      patients were included in this meta-analysis. Prevalence of hepatic fibrosis was
      evaluated in nonalcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV),
      and hepatitis C and HIV coinfection by two, four, and one studies. Progression of
      hepatic fibrosis was evaluated by two studies. Pooled OR for prevalence of
      fibrosis was 0.91 (0.72-1.15), I=75%. On subgroup analysis, pooled OR among NAFLD
      patients was 0.80 (0.75-0.86), I=0% and pooled OR among HCV patients was 1.96
      (0.78-4.92), I=77%. Among studies evaluating HR, pooled HR for progression of
      fibrosis in HCV-HIV co-infected patients was 1.03 (0.96-1.11), I=0%. CONCLUSION:
      Marijuana use did not increase the prevalence or progression of hepatic fibrosis
      in HCV and HCV-HIV-coinfected patients. On the contrary, we noted a reduction in
      the prevalence of NAFLD in marijuana users. Future studies are needed to further
      understand the therapeutic impact of cannabidiol-based formulations in the
      management of NAFLD.

PMID- 30234645
TI  - Randomized controlled trial of polyethylene glycol versus lactulose for the
      treatment of overt hepatic encephalopathy.
AB  - BACKGROUND: Overt hepatic encephalopathy (HE) is a frequent complication of
      cirrhosis and one of the most debilitating manifestations that necessitates
      hospitalization. Although many treatment modalities are being investigated, none
      of them are satisfactory. So, newer treatment modalities have to be tried.
      OBJECTIVE: To evaluate the safety and efficacy of polyethylene glycol (PEG)
      versus lactulose in the management of HE. PATIENTS AND METHODS: This clinical
      trial included 100 patients with post-hepatitis C cirrhosis who were admitted
      with HE. Patients were randomized into two equal groups: group I patients
      received lactulose and group II patients received PEG. The clinico
      epidemiological characteristics of patients, Child-Pugh score, and HE scoring
      algorithm were registered before and 24 h after administration of the drug.
      Moreover, any suspected adverse effects were recorded. RESULTS: All 100 patients
      received treatment. Three patients died within 24 h of admission and did not
      complete the follow-up period. According to intention-to-treat approach, they
      were considered as treatment failure. On analysis, 36/50 (72%) patients improved
      one grade or more in HE scoring algorithm score after 24 h of lactulose therapy
      versus 47/50 (94%) of those on PEG therapy (P<0.05). The time needed for
      resolution of HE and length of hospital stay were significantly lower in PEG
      group versus lactulose group (P<0.001). Both therapies were tolerated, and no
      significant adverse events were reported. CONCLUSION: Both lactulose and PEG were
      safe and effective in the treatment of HE. PEG significantly decreased the time
      needed for resolution of HE and significantly shortened the hospital stay.

PMID- 30234646
TI  - The role of genomic approaches in diagnosis and management of primary
      immunodeficiency.
AB  - PURPOSE OF REVIEW: Genetic testing serves an increasingly important role in the
      diagnosis and management of primary immunodeficiency. In this review, the
      strengths and limitations of various genetic testing methods are summarized,
      providing a foundation for the clinical approach to achieving a molecular
      diagnosis. RECENT FINDINGS: Rapid advances in sequencing technology have enabled
      the incorporation of comprehensive genetic testing into first-line clinical
      diagnostics. Recent articles enable comparisons of the diagnostic utility of new
      testing strategies while simultaneously reminding clinicians of the strengths of
      traditional methods. SUMMARY: Genetic testing in primary immunodeficiency cannot
      be standardized, but instead needs to be personalized based on the presenting
      phenotype and a basic understanding of the utility of different molecular
      methods. These tools, when correctly employed, can achieve a molecular diagnosis
      and inform the natural history, prognosis, recurrence risk, and therapeutic
      options.

PMID- 30234647
TI  - Retinitis pigmentosa: recent advances and future directions in diagnosis and
      management.
AB  - PURPOSE OF REVIEW: Retinitis pigmentosa is a group of genetically diverse
      inherited blinding disorders for which there are no treatments. Owing to recent
      advances in imaging technology, DNA sequencing, gene therapy, and stem cell
      biology, clinical trials have multiplied and the landscape is rapidly changing.
      This review provides a relevant and timely update of current trends and future
      directions for the diagnosis and management of this disease. RECENT FINDINGS:
      This review will highlight the use of retinal imaging to measure progression of
      disease, next-generation sequencing for genetic diagnosis, the use of electronic
      retinal implants as well as noninvasive digital low-vision aids, and the current
      state of preclinical and clinical research with gene therapy and cell-based
      therapies. SUMMARY: Retinitis pigmentosa has historically been an untreatable
      condition. Recent advances have allowed for limited improvement in visual
      outcomes for select patients. Retinal degenerative disease is on the cutting edge
      of regenerative medicine. Gene therapy and stem cell therapeutic strategies are
      currently under investigation and are expected to radically impact management of
      inherited retinal disease in the coming years. VIDEO ABSTRACT:
      http://links.lww.com/MOP/A33.

PMID- 30234648
TI  - Migraine in children: presentation, disability and response to treatment.
AB  - PURPOSE OF REVIEW: The current review presents findings from investigations of
      migraine in children. The presentation of pediatric migraine, related
      consequences, and medication treatments are reviewed. RECENT FINDINGS: A number
      of advancements have been made in the study of the presentation, disability, and
      treatments for migraine in children. However, recent research suggests that not
      all approaches are equally effective in the treatment of migraine in children.
      Specifically, a recent study comparing pharmacological interventions found that
      preventive medications were not statistically more effective than placebo in
      children. Consistent findings showing clinically meaningful placebo response
      rates, shorter duration of headaches and other characteristic features (e.g.
      frontal, bilateral location) have been barriers to the design of randomized
      clinical trials in children and adolescents with migraine. Better understanding
      of treatment mechanisms for medication interventions is needed. SUMMARY: Several
      migraine treatments have determined to be effective for use in children but few
      controlled studies have evaluated the effectiveness of medication treatments.
      Recent research suggests that preventive medications may not be more effective
      than placebo. Additional research is needed to evaluate the effectiveness of
      medication treatment in migraine headache care.

PMID- 30234649
TI  - Noninvasive Atrophic Acne Scar Treatment in Asians With a 755-nm Picosecond Laser
      Using A Diffractive Optic Lens-A Retrospective Photographic Review.
AB  - BACKGROUND: The diffractive lens of the picosecond laser is relatively new, and
      there are few reports on its efficacy in treating atrophic acne scars, especially
      in Asian populations. OBJECTIVE: Evaluating the efficacy of diffractive lens 755
      nm picosecond laser for atrophic acne scar treatment in Asians. PATIENTS AND
      METHODS: Forty-two patients who were treated for facial atrophic acne scars at a
      private dermatological clinic were enrolled in this retrospective analysis. Mean
      session count was 4.28. Before and after photographs were assessed by 2 blinded
      dermatologists, who rated the amount of overall skin quality improvement on a 5
      point scale. RESULTS: All patients experienced improvements in scar texture and
      overall skin quality after 2 to 6 sessions, with scores of +1.4, 1.45, 1.7, 1.33,
      2.3, and 1.66 points after 2, 3, 4, 5, 6, and >6 treatments, respectively. There
      were no obvious adverse effects after treatment. The postinflammatory
      hyperpigmentation (PIH) risk was 4.7% (2 of 42, both spontaneously resolved).
      CONCLUSION: The 755-nm diffractive lens picosecond laser showed good efficacy and
      low PIH rates when treating atrophic acne scars in darker skin-type patients. In
      addition to treatment results, additional improvements in overall skin quality
      and pigmentation make the picosecond laser an effective and desirable treatment
      option for Asians.

PMID- 30234650
TI  - How We Do It: Dermabrasion as a Primary Reconstruction Option for Nasal Defects.

PMID- 30234651
TI  - Large Nasal Tip Defects-Utilization of Interdomal Sutures Before Burow's Graft
      for Optimization of Nasal Contour.

PMID- 30234652
TI  - Fire Safety in Mohs Micrographic Surgery.
AB  - BACKGROUND: Surgical fire is a rare event, but one with potentially devastating
      patient outcomes. OBJECTIVE: This study was conducted to investigate the
      incidence, risk factors, and outcome of surgical fires experienced by members of
      the American College of Mohs Surgeons (ACMS). METHODS: An internet survey was
      developed and sent to ACMS members. Data collected included total years of
      experience, total number of cases, typical management of supplemental oxygen, and
      surgical fires experienced. RESULTS: Eighty participants contributed data on
      886,200 cases of MMS. Nine surgeons (11%) reported at least 1 surgical fire,
      yielding an estimated incidence of 1 fire per 88,620 cases (0.001%). The most
      common site of involvement was the scalp (67%). Common ignition sources included
      monopolar electrosurgical devices (78%) and battery-powered thermal cautery
      (22%). Fuel sources included towels or drapes, gauze, isopropyl alcohol, aluminum
      chloride, hairspray, and diethyl ether. Supplemental oxygen was not involved in
      any of the cases. Five patients suffered singed hair while 4 patients did not
      suffer any injuries. None suffered any permanent functional or aesthetic
      deformities. CONCLUSION: The overall risk of surgical fire in MMS is minimal.
      However, safety measures and greater awareness of fire risks are necessary to
      prevent patient harm.

PMID- 30234653
TI  - A Freely Mobile Subcutaneous Nodule of the Dorsal Hand.

PMID- 30234654
TI  - Disguising Scars With Decorative Tattooing: A Patient-Inspired Approach.

PMID- 30234655
TI  - Commentary on a Retrospective Case-Matched Cost Comparison of Surgical Treatment
      of Melanoma and Nonmelanoma Skin Cancer in the Outpatient Versus Operating Room
      Setting.

PMID- 30234656
TI  - Successful Treatment of Lichen Amyloidosis With Trichloroacetic Acid Peels.

PMID- 30234657
TI  - Personal (Self) Perceptions of Submental Fat Among Adults in the United States.
AB  - BACKGROUND: Satisfaction with discrete facial areas influences self-perceptions
      of attractiveness, self-esteem, and quality of life. Currently, there is a lack
      of understanding of how the submental area impacts feelings and behaviors.
      OBJECTIVE: To characterize the effects of submental fat (SMF) on
      feelings/emotions and actions/behavior among adults in the United States.
      METHODS: Online health-based surveys recruited approximately 400 adults (18-65
      years) in each of 5 categories based on the respondent's assessment of their SMF.
      Respondents either agreed or disagreed with 17 statements regarding their
      feelings/emotions and actions/behaviors related to the area underneath their
      chin. RESULTS: Overall, 1996 respondents were included (equal distribution of
      males/females; mean age, 41.9 years). Even a slight amount of chin fat was
      associated with negative feelings and behaviors. As SMF increased, so did the
      number of respondents reporting negative self-perceptions such as being
      embarrassed by the area under their chin. In general, a greater percentage of
      female compared with male respondents reported negative feelings and behavioral
      changes due to their submental area. CONCLUSION: Excess SMF can have a
      substantial negative effect on a person's feelings of attractiveness and
      behaviors. Reduction of SMF may not only improve one's appearance, but also may
      enhance one's self-esteem.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.

PMID- 30234658
TI  - Swallowing function in advanced age.
AB  - PURPOSE OF REVIEW: To present current literature regarding swallowing function in
      advanced age, including healthy ageing, dysphagia and trends in multidisciplinary
      team service delivery. RECENT FINDINGS: Normative studies support swallowing
      efficiency but greater variability in healthy advanced age, through to 100 years
      old. Deviations from normative data and symptoms of dysphagia leading to
      aspiration or nutritional risk, imply swallowing disorder, rather than simply the
      ageing process. Quantitative and qualitative studies are emerging that promote
      management of swallow dysfunction for an ageing society, including innovative
      assessment, home treatment, swallowing exercise and optimized mealtimes. SUMMARY:
      Current literature on swallowing function in advanced age provides
      multidisciplinary perspectives and initiatives, with clear commitment to
      improving quality of life for older adults. The diversity of the older population
      and serious consequences of swallowing difficulties calls for routine screening
      tools for swallowing impairment and malnutrition risk. Representation of 'oldest
      old' in future normative studies is essential to guide swallowing management in
      adults over 85 years old.

PMID- 30234659
TI  - IgG4-related disease in the head and neck.
AB  - PURPOSE OF REVIEW: To summarize current evidence regarding the pathophysiology,
      diagnostic criteria, and management of IgG4 disease in the head and neck. RECENT
      FINDINGS: The anti-CD20 antibody, rituximab is being used increasingly as a
      primary treatment modality in cases with a definitive diagnosis. Despite the
      favorable prognosis, it is now recognized that the incidence of cancer
      development within 3 years of diagnosis is higher than that of the general
      population. SUMMARY: IgG4-related disease is a sclerosing, chronic inflammatory
      disease, that is benign, and usually occurs in middle-aged to elderly
      individuals. Definitive diagnosis of IgG4-related disease requires radiological
      confirmation of enlargement of the affected organ, elevated serum IgG4 levels,
      and characteristic histopathological findings. Treatment is primarily with
      systemic corticosteroids or the monoclonal anti-CD20 antibody rituximab, surgical
      excision, or a combination of treatment modalities. Prognosis is good with
      complete remission in up to 90% of patients.

PMID- 30234660
TI  - Cervical osteophytosis and spine posture: contribution to swallow disorders and
      symptoms.
AB  - PURPOSE OF REVIEW: The article reviews the effects of cervical osteophytosis and
      spine posture on swallowing, and how they can cause dysphagia. RECENT FINDINGS:
      Cerivical osteophytosis which is a bony overgrowth of the cervical spines, it
      affects the swallowing through different mechanisms, including direct mechanical
      compression of the pharynx and esophagus, disturbances of normal epiglottic tilt
      over the inlet of the larynx by the osteophytes at C3-C4 level, inflammatory
      reactions in the tissues around the esophagus and cricopharyngeal spasm. Also,
      cervical spine posture in normal individuals could affect the swallowing
      mechanism by disturbance of the sphincteric action of the larynx and upper
      esophageal sphincter. SUMMARY: Cervical osteophytosis and abnormal cervical
      curvature may be overlooked by the Otolaryngologists as causes of swallowing
      disorders. The diagnosis is usually confirmed by radiologic study for the
      cervical spine. Cervical abnormality should be kept in mind while we are
      investigating patients with swallowing problem, and postural modification may
      help in treatment of such cases.

PMID- 30234661
TI  - High-resolution manometry: what about the pharynx?
AB  - PURPOSE OF REVIEW: High-resolution pharyngeal manometry (HRPM) is a well
      tolerated, catheter-based, method for recording the pressures and bolus flow
      generated by the pharyngeal muscles during swallowing. Despite a body of
      published evidence and a critical mass of investigators in the field, there is a
      lack of consensus surrounding what biomechanical phenomena to measure. The
      purpose of this review is to provide some insights into the information on
      swallowing physiology that can be gathered using HRPM. RECENT FINDINGS: HRPM
      literature has focused on measuring biomechanical phenomena that may be relevant
      to measure in relation to dysphagia research. This review focuses on the
      measurement of pharyngeal luminal occlusive forces, intrabolus distension
      pressure, bolus presence and bolus flow timing as key features of pharyngeal
      swallowing that require measurement and allow for derivation of the Swallow Risk
      Index, a global measure of swallow function indicative of swallowing functional
      reserve. SUMMARY: HRPM allows objective derivation of measures of swallow
      function that may have value for diagnosis and research in relation to swallowing
      disorders. HRPM has demonstrated clinical applicability in specific patient
      populations and offers unique advantages that compliment current assessment
      methods.

PMID- 30234662
TI  - Techniques for evaluation and management of tongue-base obstruction in pediatric
      obstructive sleep apnea.
AB  - PURPOSE OF REVIEW: Tongue-base obstruction (TBO) is a common cause of persistent
      obstructive sleep apnea (OSA) after tonsillectomy and adenoidectomy in children.
      This review discusses available diagnostic modalities and surgical treatment
      options for the management of TBO. RECENT FINDINGS: Recently, a systematic review
      that included nine studies using drug-induced sleep endoscopy (DISE) in the
      evaluation of children with persistent OSA after tonsillectomy and adenoidectomy
      identified the tongue-base as the most common site of obstruction. SUMMARY: TBO
      is a common and correctable cause of persistent OSA in children. Diagnostic
      modalities include awake flexible laryngoscopy, plain neck films, DISE, and cine
      MRI. Because DISE and cine MRI are performed in a sleep-like state, they are
      fairly reliable in identifying the site of obstruction. As continuous positive
      airway pressure is often poorly tolerated in the pediatric population, there is
      considerable interest in surgical options for TBO. Depending on the location and
      the severity of the obstruction, interventions such as lingual tonsillectomy,
      posterior midline glossectomy, tongue suspension suture, epiglottopexy,
      hypoglossal nerve stimulation, tongue-lip adhesion, and hyoid suspension may play
      a role in management.

PMID- 30234663
TI  - Tympanostomy tube otorrhea in children: prevention and treatment.
AB  - PURPOSE OF REVIEW: One in two children treated with tympanostomy tubes,
      experience episodes of otorrhea whilst their tubes are in place. In this review,
      we present the results of the most recent publications on prevention and
      treatment of tympanostomy tube otorrhea (TTO). RECENT FINDINGS: Recent systematic
      reviews on water precautions for children with tympanostomy tubes support the
      American Academy of Otolaryngology - Head and Neck Surgery guideline
      recommendation against such preventive measures as there is no evidence that it
      protects against TTO. Studies on tympanostomy tube design and material suggest
      that silicone tubes have a lower TTO risk and that biofilms appear to be mainly
      located in the perpendicular junction of the T-tubes and the round rims of the
      Paparella-type tubes. Another study shows that the biofilm-component DNAB-II
      protein is present in otorrhea of half of children with TTO. Targeting this
      protein could lead to a collapse of the biofilm structure and as such a potential
      new treatment for chronic TTO. New systematic reviews show that antibiotic
      eardrops are the most effective first-line treatment of acute TTO and suggest
      that an antibiotic-corticosteroid combination is more effective than antibiotic
      only. Although in many countries, quinolone eardrops are the preferred choice
      because of being non-ototoxic, one study found a higher risk of persistent
      perforation after tube extrusion in children treated with quinolone eardrops as
      compared with children treated with aminoglycoside eardrops. SUMMARY: Recent
      evidence confirms that water precautions for children with tympanostomy tubes are
      not effective in preventing TTO. Antibiotic-corticosteroid eardrops are the most
      effective treatment of acute TTO.

PMID- 30234664
TI  - Laryngopharyngeal reflux disease: clinical presentation, diagnosis and
      therapeutic challenges in 2018.
AB  - PURPOSE OF REVIEW: To review the recent literature on presentation, diagnosis and
      treatment of laryngopharyngeal reflux. RECENT FINDINGS: Patients with
      laryngopharyngeal reflux have a higher risk for gastroesophageal reflux and
      respiratory-related diseases. Many symptoms and findings are underestimated,
      contributing to the inconclusive results of many therapeutic trials.
      Additionally, little significance is given to nonacid and mixed refluxates,
      although a significant prevalence. The association between symptoms, signs,
      impedance-pH studies and pepsin detection could be the most accurate way for a
      clear diagnosis. 'Reflux profiling' is also important for the administration of a
      personalized treatment based on diet, proton pump inhibitors, alginate,
      magaldrate and other second-line drugs. There are only a handful of studies
      focusing on the addition of alginate or magaldrate to the treatment of
      laryngopharyngeal reflux, although their contribution has extensively been
      demonstrated. SUMMARY: Diagnosis remains controversial despite improvement in
      impedance and availability of pepsin detection in daily practice. With recent
      studies exhibiting a significant prevalence of nonacid or mixed refluxes, the
      addition of alginate or magaldrate to proton pump inhibitors should be
      considered. Future studies are needed to assess these new therapeutic schemes in
      moderate and severe laryngopharyngeal reflux.

PMID- 30234665
TI  - Patient-Reported Outcomes in First-Line Antiretroviral Therapy: Results From
      NEAT001/ANRS143 Trial Comparing Darunavir/Ritonavir in Combination With
      Tenofovir/Emtricitabine or Raltegravir.
AB  - BACKGROUND: There are few data comparing patient-reported outcomes (PROs) in
      randomized trials of initial antiretroviral therapy. We present results from a
      substudy of the NEAT001/ANRS143 trial. METHODS: The randomized trial compared
      first-line DRV/r 800/100 mg once daily plus RAL 400 mg twice daily and DRV/r plus
      TDF/FTC 245/200 mg once daily. Changes in PROs were assessed with 3
      questionnaires: EuroQoL 5 domains (EQ-5D), Center for Epidemiologic Studies
      Depression (CES-D) scale, and HIV Treatment Satisfaction Questionnaire. Major
      depressive disorder (MDD) was defined as CES-D >= 16. General estimating
      equations were used to model change over 96 weeks in PROs from baseline. RESULTS:
      Of the 805 participants, 797 (99%) contributed to the substudy. Baseline PRO data
      were similar for the 2 randomized groups. Health status improved over time with a
      mean increase in EQ-5D visual analogue scale (VAS) of 8.0 by W96 [95% confidence
      interval (CI): 6.5 to 9.4; P < 0.001], and no statistically significant
      differences between groups (difference of 0.3 on VAS score (95% CI: -1.7 to 2.3);
      P = 0.7, global P value >=0.05 for all domains over follow-up). There was no
      significant difference between groups on CES-D [difference of -0.1 (95% CI: -1.3
      to 1.1); P = 0.9], or MDD during follow-up, adjusted for baseline MDD (odds ratio
      = 0.98, 95% CI: 0.82 to 1.18; P = 0.9). RAL + DRV/r group had lower level of
      convenience (P = 0.03) and fitted less well into patients' lifestyle (P = 0.007)
      than the TDF/FTC + DRV/r regimen, and was associated with lower treatment
      satisfaction [median score: 53 RAL + DRV/r vs 55 TDF/FTC + DRV/r (P = 0.001)].
      CONCLUSION: PROs improved after starting antiretroviral therapy, with no
      statistically significant difference between groups. The lower satisfaction with
      RAL + DRV/r may be explained by twice-daily administration.

PMID- 30234666
TI  - ICU mortality and variables associated with ICU survival in Poland: A nationwide
      database study.
AB  - BACKGROUND: Recently published international comparison data across European
      countries revealed high mortality rates in Polish ICUs. OBJECTIVES: Estimation of
      the rate of ICU mortality and identification of variables associated with ICU
      survival in Poland. DESIGN: Retrospective analyses of a database reporting ICU
      stays in Poland. SETTINGS AND PATIENTS: The study included data from all adult
      patients admitted to an ICU in Poland from 1 January 2012 to 31 December 2012.
      MAIN OUTCOME MEASURES: ICU mortality and variables associated with ICU survival.
      RESULTS: A total of 48 282 patients were treated in 347 ICUs (mean age 63.1 +/-
      16.8 years, 59% men) with 20 278 deaths (42.0%). Variables associated with ICU
      survival were: tertiary level of hospital care [relative risk (RR) 0.86, 95%
      confidence interval (CI) 0.80 to 0.92, P < 0.001]; high annual patient volume in
      the ICU (RR 0.9995 patient year, 95% CI 0.9994 to 0.9996, P < 0.001); younger
      patient age (RR 1.025 year, 95% CI 1.024 to 1.026, P < 0.001); female sex (RR
      0.92, 95% CI 0.88 to 0.96; P < 0.001); and lower number of comorbidities (RR
      1.33, 95% CI 1.31 to 1.35, P < 0.001). CONCLUSION: ICU mortality was high in
      Poland. Structural variables, such as the level of hospital care and annual
      patient volume, may be associated with ICU survival.

PMID- 30234667
TI  - The degree of adherence to CONSORT reporting guidelines for the abstracts of
      randomised clinical trials published in anaesthesia journals: A cross-sectional
      study of reporting adherence in 2010 and 2016.
AB  - BACKGROUND: Abstracts are intended to be concise summaries of the entire
      randomised clinical trial (RCT). Despite their importance, few studies have
      examined the reporting quality of abstracts in the anaesthesiology literature.
      OBJECTIVES: To examine the quality of RCT abstract reporting according to the
      CONSORT for Abstracts guidelines and determine whether recommended items omitted
      from the abstract were present in the body of the article. DESIGN: A cross
      sectional study of RCTs. SETTING: This study was performed at the University of
      Western Ontario and University Hospital, London Health Sciences Centre.
      PARTICIPANTS: All RCTs meeting inclusion criteria that were published in 2010 or
      2016 in six general anaesthesiology journals (Anaesthesia, Anesthesia &
      Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of
      Anesthesia and European Journal of Anaesthesiology). MAIN OUTCOME MEASURES: The
      16 checklist items from the CONSORT for Abstracts statement were used to create a
      convenience score as a proxy for RCT abstract reporting quality, with each
      criterion measured as being reported in abstract, not reported in abstract but
      reported in full-text article, or not reported in abstract or full-text article.
      RESULTS: Of the 395 RCTs identified, 219 were published in 2010 and 176 were
      published in 2016. Out of the maximum possible score of 16, the median abstract
      score increased from 4 points [interquartile range (IQR): 3 to 5] in 2010 to 6
      points [IQR: 5 to 8] in 2016. Although most checklist items showed improvement
      from 2010 to 2016, around 75% of RCTs in 2016 met fewer than half of the 16 items
      with no RCTs reporting all 16 items in the abstract. A majority of the RCTs had
      the information present in the full-text. In 2016, only 71 out of 176 (40%) of
      RCTs reported outcomes conforming to the CONSORT guidelines (with an effect size
      and a confidence interval around the effect size) in the Abstract. CONCLUSION:
      Abstracts for many anaesthesiology RCTs are incomplete selective summaries of the
      entire article.

PMID- 30234668
TI  - How current transfusion practices in geriatric patients with hip fracture still
      differ from current guidelines and the effects on outcome: A retrospective
      observational study.
AB  - BACKGROUND: Transfusion guidelines have become increasingly restrictive. We
      investigated actual transfusion practices in geriatric hip fracture patients, why
      they differ from current guidelines and how this affects outcome. OBJECTIVES: The
      primary aim was to examine transfusion timing, evaluate how many red blood cell
      (RBC) transfusions are in keeping with guidelines and how this affects morbidity
      (infection, cardiac events and delirium), mortality and length of stay (LOS). Our
      secondary aim was to test the hypothesis that guidelines were more likely to be
      deviated from shortly before discharge and with consecutive transfusions. DESIGN:
      A retrospective observational study. SETTING: The Luzerner Kantonsspital, a major
      trauma centre, over a 12-month period from 1 February 2015 to 31 January 2016.
      PATIENTS: All patients over 70 years of age admitted to the Luzerner
      Kantonsspital with hip fractures over a 12-month period in 2015 to 2016 were
      included. RESULTS: 156 patients were included, to which 141 units of RBCs were
      transfused. All pre and intra-operative transfusions were according to
      guidelines; 110 transfusions were postoperative and 37 of these were not
      according to guidelines. Patients who were transfused had longer LOS in hospital
      (P = 0.002) and an odds ratio (OR) of 2.7 of contracting an infection (P = 0.04)
      in comparison with patients who were not transfused. No significant differences
      in mortality, LOS or morbidity were found between patients transfused according
      to guidelines and more liberal thresholds. Guidelines were more likely to be
      deviated from within the last 2 days before discharge than prior to this (58 vs.
      24%, P = 0.03). Furthermore, 24 stable patients received two consecutive RBC
      units resulting in posttransfusion haemoglobin values of between 83 and 124 g l.
      CONCLUSION: Most RBC transfusions occur postoperatively, many still according to
      liberal transfusion thresholds, in particular shortly before discharge and as
      part of consecutive transfusions. Transfused patients had longer LOS and more
      infections than patients not transfused, but there was no difference in
      mortality, LOS or morbidity between patients transfused according to current
      guidelines and those where guidelines were deviated from.

PMID- 30234669
TI  - The effect of virtual reality bronchoscopy simulator training on performance of
      bronchoscopic-guided intubation in patients: A randomised controlled trial.
AB  - BACKGROUND: The use of a flexible optical bronchoscopic (FOB) for intubation is
      an essential airway management skill. OBJECTIVE(S): Our primary objective was to
      compare the effects of simulator training (ORSIM high-fidelity simulator) with no
      simulation training on the performance of FOB intubation in anaesthetised
      patients. DESIGN: Randomised controlled trial. SETTING: Single-centre tertiary
      hospital; trial conducted between April 2015 to May 2016. PARTICIPANTS: Medical
      students, anaesthesia assistants and anaesthesia residents with experience of
      less than five FOB intubations from whom informed consent was obtained.
      INTERVENTION: Students, anaesthesia assistants and anaesthesia residents viewed a
      didactic presentation before performing an initial FOB intubation in an
      anaesthetised patient. Intubations were recorded and evaluated using the Global
      Rating Scale (GRS) and checklist scores. Subsequently, participants were
      randomised to control group (Group CON) and had no simulation training, or to a
      simulation group (Group SIM) and underwent 60 min of simulation practice. Within
      a week, participants performed a second FOB intubation and were similarly
      evaluated. MAIN OUTCOME MEASURES: Pretraining and posttraining intubation time,
      GRS and checklist scores. RESULTS: Baseline characteristics were similar between
      groups. In Group SIM, there was significant improvement between pre and
      posttraining GRS [22.9 +/- 8.1 vs. 28.2 +/- 7.3, mean difference (95% CI) 5.3
      (0.3 to 10.3), P = 0.04], and intubation time [177.6 +/- 77.6 vs. 119.3 +/- 52.2
      s, mean difference (95% CI) -58.4 (-100.3 to -16.5) s, P = 0.01]. There was no
      difference in Group CON, between pre and posttraining intubation time, GRS or
      checklist. CONCLUSION: We conclude, posttraining performance of FOB intubation,
      as measured by intubation time and GRS, improved in Group SIM, while it was
      unchanged in the Group CON. The ORSIM simulator may be a useful adjunct in
      acquiring FOB intubation skills. CLINICAL TRIAL NUMBER AND REGISTRY:
      ClinicalTrials.gov ID: NCT02699242.

PMID- 30234670
TI  - Expanding Contraceptive Access for Women With Substance Use Disorders:
      Partnerships Between Public Health Departments and County Jails.
AB  - CONTEXT: Law enforcement has been the primary strategy for addressing the opioid
      epidemic. As a result, the incarceration rate for women in county jails has
      increased more than 800% since 1980, and most women inmates struggle with
      substance use disorders. There is a large unmet need for contraception among
      women in county jails. PROGRAM: The East Region of the Tennessee Department of
      Health partnered with county correctional facilities to provide comprehensive
      family planning education and voluntary long-acting reversible contraception
      (LARC) to women in 15 jails. IMPLEMENTATION: Incarcerated women were invited to
      attend a comprehensive family planning education session conducted in the jail by
      health department nurses. The sessions included information on neonatal
      abstinence syndrome. The nurses explained that the women could receive
      intrauterine devices, implants, and injectable progesterone while incarcerated
      and come to the health department for all contraceptive methods upon release.
      Between January 2014 and June 2017, nurses conducted 182 education sessions, and
      794 women received a LARC. Method placement occurred in the jails or at the local
      health department. No adverse effects were known to have occurred. EVALUATION: We
      collected pilot data to explore the accuracy and the comprehensiveness of the
      family planning education session and whether the incarcerated women experienced
      the program as voluntary. All 18 women inmates interviewed reported experiencing
      the program as voluntary. Using published and administrative data, we roughly
      estimated that the program prevented between 270 and 460 unintended pregnancies
      and between 40 and 52 cases of neonatal abstinence syndrome in the first year
      after the women received a method. This represents a cost savings to Medicaid of
      $1.4 million. DISCUSSION: The partnership demonstrated the feasibility of
      providing voluntary comprehensive family planning education and access to highly
      effective contraception for women inmates who, as a group, face a host of
      political, socioeconomic, and personal barriers to reproductive health care.

PMID- 30234671
TI  - Ultrasonographic Features of Lower-Limb Joints in Gout: Which Joints and Clinical
      Characteristics Would Provide More Information for Diagnosis?
AB  - OBJECTIVE: This observational cross-sectional study evaluated the distribution of
      ultrasound (US) features of lower-limb joints and the risk factors of tophus in
      gout patients. METHODS: We examined 588 joints including the bilateral knee,
      ankle, and first metatarsophalangeal (MTP) joints in 98 gout patients by US
      between March to August in 2017. The distribution of double-contour (DC), tophus,
      aggregates, synovitis, effusion and erosion in different joint, course, and age
      groups were investigated by Cochran Q and chi test. The risk factors of tophus
      were analyzed using logistic regression method. RESULTS: Double-contour was most
      commonly observed in the knee (P = 0.005). Tophus, aggregates, synovitis, and
      erosion were mostly detected in the first MTP (P < 0.001, P = 0.01, P = 0.001, P
      < 0.001, respectively). The prevalence rates of DC, tophus, and erosion in
      patients with a longer course were significantly higher (P = 0.029, P = 0.002, P
      < 0.001, respectively). Older patients had more detectable tophus and erosion
      than younger patients (P = 0.028, P = 0.021). Patients of older age (odds ratio
      [OR], 3.83; 95% confidence interval [CI], 1.27-11.48), with frequent attacks (OR,
      3.80; 95% CI, 1.10-13.15), and with longer course (OR, 6.52; 95% CI, 1.37-30.96)
      had higher risks of tophus. CONCLUSIONS: Most signs were detected by US in the
      first MTP, except that DC was most commonly observed in the knees. Patients of
      older age with frequent attacks and longer course may experience higher risks for
      tophus. Comprehensive assessment of the lower limbs, particularly the knee and
      first MTP, can significantly help diagnosis.

PMID- 30234672
TI  - Where Have All the Patients Gone? Profile of US Adults Who Report Doctor
      Diagnosed Arthritis But Are Not Being Treated.
AB  - BACKGROUND: Patients only benefit from clinical management of arthritis if they
      are under the care of a physician or other health professional. OBJECTIVES: We
      profiled adults who reported doctor-diagnosed arthritis who are not currently
      being treated for it to understand better who they are. METHODS: Individuals with
      no current treatment (NCT) were identified by "no" to "Are you currently being
      treated by a doctor or other health professional for arthritis or joint
      symptoms?" Demographics, current symptoms, physical functioning, arthritis
      limitations and interference in life activities, and level of agreement with
      treatment and attitude statements were assessed in this cross-sectional,
      descriptive study of noninstitutionalized US adults aged 45 years or older with
      self-reported, doctor-diagnosed arthritis (n = 1793). RESULTS: More than half of
      the study population, 52%, reported NCT (n = 920). Of those with NCT, 27%
      reported fair/poor health, 40% reported being limited by their arthritis, 51% had
      daily arthritis pain, 59% reported 2 or more symptomatic joints, and 19% reported
      the lowest third of physical functioning. Despite NCT, 83% with NCT agreed or
      strongly agreed with the importance of seeing a doctor for diagnosis and
      treatment. CONCLUSIONS: Greater than half of those aged 45 years or older with
      arthritis were not currently being treated for it, substantial proportions of
      whom experienced severe symptoms and poor physical function and may benefit from
      clinical management and guidance, complemented by community-delivered public
      health interventions (self-management education, physical activity). Further
      research to understand the reasons for NCT may identify promising intervention
      points to address missed treatment opportunities and improve quality of life and
      functioning.

PMID- 30234673
TI  - Efficacy and Safety of Methotrexate for the Treatment of Autoimmune Virus
      Negative Myocarditis: A Case Series.

PMID- 30234674
TI  - Implementation of a Risk-Stratified Opioid and Benzodiazepine Weaning Protocol in
      a Pediatric Cardiac ICU.
AB  - OBJECTIVES: Opioids and benzodiazepines are commonly used to provide analgesia
      and sedation for critically ill children with cardiac disease. These medications
      have been associated with adverse effects including delirium, dependence,
      withdrawal, bowel dysfunction, and potential neurodevelopmental abnormalities.
      Our objective was to implement a risk-stratified opioid and benzodiazepine
      weaning protocol to reduce the exposure to opioids and benzodiazepines in
      pediatric patients with cardiac disease. DESIGN: A prospective pre- and
      postinterventional study. PATIENTS: Critically ill patients less than or equal to
      21 years old with acquired or congenital cardiac disease exposed to greater than
      or equal to 7 days of scheduled opioids +/- scheduled benzodiazepines between
      January 2013 and February 2015. SETTING: A 24-bed pediatric cardiac ICU and 21
      bed cardiovascular acute ward of an urban stand-alone children's hospital.
      INTERVENTION: We implemented an evidence-based opioid and benzodiazepine weaning
      protocol using educational and quality improvement methodology. MEASUREMENTS AND
      MAIN RESULTS: One-hundred nineteen critically ill children met the inclusion
      criteria (64 post intervention, 55 pre intervention). Demographics and risk
      factors did not differ between groups. Patients in the postintervention period
      had shorter duration of opioids (19.0 vs 30.0 d; p < 0.01) and duration of
      benzodiazepines (5.3 vs 22.7 d; p < 0.01). Despite the shorter duration of wean,
      there was a decrease in withdrawal occurrence (% Withdrawal Assessment Tool score
      >= 4, 4.9% vs 14.1%; p < 0.01). There was an 8-day reduction in hospital length
      of stay (34 vs 42 d; p < 0.01). There was a decrease in clonidine use (14% vs
      32%; p = 0.02) and no change in dexmedetomidine exposure (59% vs 75%; p = 0.08)
      in the postintervention period. CONCLUSIONS: We implemented a risk-stratified
      opioid and benzodiazepine weaning protocol for critically ill cardiac children
      that resulted in reduction in opioid and benzodiazepine duration and dose
      exposure, a decrease in symptoms of withdrawal, and a reduction in hospital
      length of stay.

PMID- 30234675
TI  - Development and Implementation of a Bedside Peripherally Inserted Central
      Catheter Service in a PICU.
AB  - OBJECTIVES: To create a bedside peripherally inserted central catheter service to
      increase placement of bedside peripherally inserted central catheter in PICU
      patients. DESIGN: Two-phase observational, pre-post design. SETTING: Single
      center quaternary noncardiac PICU. PATIENTS: All patients admitted to the PICU.
      INTERVENTIONS: From June 1, 2015, to May 31, 2017, a bedside peripherally
      inserted central catheter service team was created (phase I) and expanded (phase
      II) as part of a quality improvement initiative. A multidisciplinary team
      developed a PICU peripherally inserted central catheter evaluation tool to
      identify amenable patients and to suggest location and provider for procedure
      performance. Outcome, process, and balancing metrics were evaluated. MEASUREMENTS
      AND MAIN RESULTS: Bedside peripherally inserted central catheter service placed
      130 of 493 peripherally inserted central catheter (26%) resulting in 2,447
      hospital central catheter days. A shift in bedside peripherally inserted central
      catheter centerline proportion occurred during both phases. Median time from
      order to catheter placement was reduced for peripherally inserted central
      catheters placed by bedside peripherally inserted central catheter service
      compared with placement in interventional radiology (6 hr [interquartile range, 2
      23 hr] vs 34 hr [interquartile range, 19-61 hr]; p < 0.001). Successful access
      was achieved by bedside peripherally inserted central catheter service providers
      in 96% of patients with central tip position in 97%. Bedside peripherally
      inserted central catheter service central line-associated bloodstream infection
      and venous thromboembolism rates were similar to rates for peripherally inserted
      central catheters placed in interventional radiology (all central line-associated
      bloodstream infection, 1.23 vs 2.18; p = 0.37 and venous thromboembolism, 1.63 vs
      1.57; p = 0.91). Peripherally inserted central catheters in PICU patients had
      reduced in-hospital venous thromboembolism rate compared with PICU temporary
      catheter in PICU rate (1.59 vs 5.36; p < 0.001). CONCLUSIONS: Bedside
      peripherally inserted central catheter service implementation increased bedside
      peripherally inserted central catheter placement and employed a patient-centered
      and timely process. Balancing metrics including central line-associated
      bloodstream infection and venous thromboembolism rates were not significantly
      different between peripherally inserted central catheters placed by bedside
      peripherally inserted central catheter service and those placed in interventional
      radiology.

PMID- 30234676
TI  - Ventilator-Associated Pneumonia and Events in Pediatric Intensive Care: A Single
      Center Study.
AB  - OBJECTIVES: Ventilator-associated pneumonia is the second most common nosocomial
      infection in pediatric intensive care. The Centers for Disease Control and
      Prevention recently issued diagnosis criteria for pediatric ventilator-associated
      pneumonia and for ventilator-associated events in adults. The objectives of this
      pediatric study were to determine the prevalence of ventilator-associated
      pneumonia using these new Centers for Disease Control and Prevention criteria, to
      describe the risk factors and management of ventilator-associated pneumonia, and
      to assess a simpler method to detect ventilator-associated pneumonia with
      ventilator-associated event in critically ill children. DESIGN: Retrospective,
      observational, single-center. SETTING: PICU in a tertiary-care university
      hospital. PATIENTS: Consecutive critically ill children mechanically ventilated
      for greater than or equal to 48 hours between November 2013 and November 2015.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 304 patients mechanically
      ventilated for greater than or equal to 48 hours, 284 were included. Among them,
      30 (10.6%) met clinical and radiologic Centers for Disease Control and Prevention
      criteria for ventilator-associated pneumonia, yielding an prevalence of 7/1,000
      mechanical ventilation days. Median time from mechanical ventilation onset to
      ventilator-associated pneumonia diagnosis was 4 days. Semiquantitative culture of
      tracheal aspirates was the most common microbiological technique. Gram-negative
      bacteria were found in 60% of patients, with a predominance of Haemophilus
      influenzae and Pseudomonas aeruginosa. Antibiotic therapy complied with adult
      guidelines. Compared with patients without ventilator-associated pneumonia, those
      with ventilator-associated pneumonia had significantly longer median durations of
      mechanical ventilation (15 vs 6 d; p < 0.001) and PICU stay (19 vs 9 d; p <
      0.001). By univariate analysis, risk factors for ventilator-associated pneumonia
      were younger age, reintubation, acute respiratory distress syndrome, and
      continuous enteral feeding. Among the 30 patients with ventilator-associated
      pneumonia, 17 met adult ventilator-associated event's criteria (sensitivity,
      56%). CONCLUSIONS: Ventilator-associated pneumonia is associated with longer
      times on mechanical ventilation and in the PICU. Using the ventilator-associated
      event criteria is of interest to rapidly screen for ventilator-associated
      pneumonia in children. However, sensitivity must be improved by adapting these
      criteria to children.

PMID- 30234677
TI  - Analysis of Patient Characteristics and Risk Factors for Thrombosis After Surgery
      for Congenital Heart Disease.
AB  - OBJECTIVES: Thrombosis is a cause of morbidity in 4-15% of children who undergo
      pediatric cardiac surgery. Data on how to prevent this complication are sorely
      needed. We aimed to identify risk factors for thrombosis following pediatric
      cardiac surgery and determine if use of low molecular weight heparin prophylaxis
      is associated with a reduction in thrombosis risk. DESIGN: Retrospective cohort
      study. SETTING: Tertiary pediatric cardiovascular ICU. PATIENTS: Patients who
      underwent cardiac surgery between June 2014 and December 2015. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Data from patients with venous or arterial
      thrombosis confirmed by radiologic studies were matched two-to-one to controls
      based on age, Society of Thoracic Surgeons-European Association for Cardio
      Thoracic Surgery mortality category, and gender. Thrombosis was detected in 33
      patients (6.2%): 25 patients (76%) had venous thromboses, five patients (15%) had
      arterial thromboses, and three patients (9%) had both. Median time to thrombosis
      detection was 13 days (25-75%; 7-31 d). On multivariate analysis, which included
      adjustment for postoperative disease severity, fresh frozen plasma exposure was
      independently associated with thrombosis (odds ratio, 3.7; 95% CI, 1.4-9.4).
      Twenty-eight patients (85%) had central venous catheter-related thromboses. Low
      molecular weight heparin prophylaxis use in this subset of patients was not
      statistically different from controls (50% vs 45%, respectively; p = 0.47). On
      multivariable analysis, fresh frozen plasma exposure was also independently
      associated with central venous catheter-related thrombosis (odds ratio, 3.6; 95%
      CI, 1.2-10.6). CONCLUSIONS: The occurrence of thrombosis after pediatric cardiac
      surgery at our institution was 6.2%, similar to what has been reported in other
      studies, despite frequent use of low molecular weight heparin. Further study is
      needed to determine the role of low molecular weight heparin for
      thromboprophylaxis and the relationship between fresh frozen plasma and
      thrombosis risk in children who undergo cardiac surgery.

PMID- 30234678
TI  - Impact of Synchronous Telemedicine Models on Clinical Outcomes in Pediatric Acute
      Care Settings: A Systematic Review.
AB  - OBJECTIVES: To evaluate the impact of synchronous telemedicine models on the
      clinical outcomes in pediatric acute care settings. DATA SOURCES: Citations from
      EBM Reviews, MEDLINE, EMBASE, Global Health, PubMed, and CINAHL. STUDY SELECTION:
      We identified studies that evaluated the impact of synchronous telemedicine on
      clinical outcomes between January 2000 and April 2018. All studies involving
      acutely ill children in PICUs, pediatric cardiac ICUs, neonatal ICUs, and
      pediatric emergency departments were included. Publication inclusion criteria
      were study design, participants characteristics, technology type, interventions,
      settings, outcome measures, and languages. DATA EXTRACTION: Two authors
      independently screened each article for inclusion and extracted information,
      including telecommunication method, intervention characteristics, sample
      characteristics and size, outcomes, and settings. DATA SYNTHESIS: Out of the 789
      studies initially identified, 24 were included. The six main outcomes of interest
      published were quality of care, hospital and standardized mortality rate,
      transfer rate, complications and illness severity, change in medical management,
      and length of stay. The use of synchronous telemedicine results improved quality
      of care and resulted in a decrease in the transfer rate (31-87.5%) (four
      studies), a shorter length of stay (8.2 vs 15.1 d) (six studies), a change or
      reinforcement of the medical care plan, a reduction in complications and illness
      severity, and a low hospital and standardized mortality rate. Overall, the
      quality of the included studies was weak. CONCLUSIONS: Despite the broad
      recommendations found for using telemedicine in pediatric acute care settings,
      high-quality evidence of its impacts is still lacking. Further robust studies are
      needed to better determine the clinical effectiveness and the associated impacts
      of telemedicine in pediatric acute care settings.

PMID- 30234679
TI  - Development of Cell Analysis Software to Evaluate Fibroblastic Changes in
      Cultivated Corneal Endothelial Cells for Quality Control.
AB  - PURPOSE: To develop software to evaluate the fibroblastic morphological changes
      in cultured human corneal endothelial cells (HCECs) as a quality control measure
      for use in tissue engineering therapy. METHODS: Software was designed to
      recognize cell borders, to approximate cell shape as an ellipse, and to calculate
      the aspect ratio of the ellipse as an indicator of severity of the fibroblastic
      morphological change. Using the designed software, 60 phase contrast images of
      polygonal HCECs and 60 phase contrast images of fibroblastic HCECs were analyzed.
      The correlations of the aspect ratio and other parameters (cell density,
      percentage of cells surrounded by 6 cells, and coefficient of variation) were
      evaluated. RESULTS: Cell shapes were recognized based on phase contrast images
      and were approximated as ellipses by software. The average aspect ratio was
      significantly higher (34.9% +/- 6.1%) in fibroblastic HCECs than in polygonal
      HCECs (24.4% +/- 2.3%) (P < 0.01). The aspect ratio showed a correlation with
      cell density, with the percentage of cells surrounded by 6 neighboring cells, and
      with the coefficient of variation (Pearson correlation coefficients, -0.84, 
      0.38, and 0.66, respectively). CONCLUSIONS: We propose that fibroblastic
      alteration of HCECs can be evaluated by the cell morphology based on the aspect
      ratio. Software developed in this study, which can analyze the frequency and
      severity of fibroblastic alteration, will be useful for nondestructive assessment
      of cells destined for use in cell-based therapy for corneal endothelial
      decompensation.

PMID- 30234682
TI  - Left main coronary artery external compression by lung adenocarcinoma
      successfully treated with percutaneous coronary intervention.

PMID- 30234681
TI  - Isolated Primary Corneal Acremonium Eumycetoma: Case Report and Literature
      Review.
AB  - PURPOSE: To report an unusual case of isolated Acremonium eumycetoma presenting
      as a protuberant mass over the cornea. METHODS: Case report and literature
      review. RESULTS: A 55-year-old male patient referred to our center with a case of
      perforated corneal ulcer with uveal tissue prolapse was examined in the casualty
      department and found to have central melt, approximately 8 mm, along with
      suspected uveal tissue prolapse. A provisional diagnosis of sloughed corneal
      ulcer with uveal prolapse was made along with differential diagnoses of fungal
      ball and infected foreign body granuloma. Tectonic penetrating keratoplasty under
      general anesthesia was planned. Intraoperatively, the suspected uveal (brown
      colored) tissue was found to be an epicorneal mass growing over an intact and
      infiltrated cornea. Histopathological and microbiological analysis of the
      epicorneal mass and host cornea revealed it to be a fungal ball (mass full of
      septate hyphae) with growth of Acremonium species on culture. The patient was
      administered topical and oral antifungal agents postoperatively, in addition to
      topical antibiotics and cycloplegics. CONCLUSIONS: Isolated corneal Acremonium
      eumycetoma masquerading as a perforated corneal ulcer with prolapsed uveal tissue
      is a rare entity. Surgical intervention and appropriate antimicrobial therapy are
      key to successful outcome.

PMID- 30234680
TI  - Association Between Season, Temperature and Causative Organism in Microbial
      Keratitis in the UK.
AB  - PURPOSE: Microbial keratitis (MK) is a major cause of corneal blindness
      worldwide. Variations in season and temperature can affect MK incidence due to
      specific causative organisms; however, few studies have examined these factors in
      the UK. METHODS: Retrospective review of all corneal scrapes from patients with
      MK presenting to Manchester Royal Eye Hospital, UK, between January 2004 and
      December 2015. Manchester's monthly temperature data were obtained from Met
      Office UK. Analysis was performed using logistic regression. RESULTS: From 4229
      corneal scrapes, 1539 organisms grew (90.6% bacteria, 7.1% fungi, and 2.3%
      Acanthamoebae sp.). Gram-positive bacteria grew with increasing temperature [odds
      ratio (OR) 1.62, 95% CI: 1.11-2.39, P = 0.014], and fungi grew with decreasing
      temperature (OR 0.29, 95% CI: 0.16-0.51, P < 0.001). Moraxella sp. grew with
      decreasing temperature (OR 0.91, 95% CI: 0.86-0.96, P = 0.001). Compared with
      winter, overall culture positivity was significantly less likely in summer (OR
      0.57, 95% CI: 0.38-0.87, P = 0.008) and spring (OR 0.65, 95% CI: 0.43-0.99, P =
      0.045). Gram-negative bacteria were more likely in summer (OR 1.48, 95% CI: 1.06
      2.09, P = 0.022) and autumn (OR 1.75, 95% CI: 1.24-2.47, P = 0.001). Candida sp.
      were less likely in summer (OR 0.25, 95% CI: 0.07-0.82, P = 0.027) and autumn (OR
      0.18, 95% CI: 0.05-0.62, P = 0.009), and Acanthamoeba sp. were less likely in
      summer (OR 0.39, 95% CI: 0.15-0.92, P = 0.037) and spring (OR 0.26, 95% CI: 0.08
      0.69, P = 0.011). CONCLUSIONS: Herein we report variation in the incidence of MK
      causing organisms by season and temperature; this finding may aid clinicians in
      predicting possible causative organisms for MK at differing times of the year.

PMID- 30234683
TI  - Asymptomatic three-vessel total coronary occlusions and acute ischemic shock in a
      cocaine addict.

PMID- 30234684
TI  - Multimodality imaging, single center, cross-sectional study in adolescents or
      young adults with repaired tetralogy of Fallout.
AB  - BACKGROUND: Proper integration of multiple imaging modalities in the routine
      follow-up of patients with repaired tetralogy of Fallout (TOF) is poorly
      supported by data. We report our single center comparative study between cardiac
      magnetic resonance (CMR) and echocardiography to assess equipoise in the clinical
      utility of these two imaging methods in an unselected consecutive cohort of TOF
      patients referred to our outpatient clinic. MATERIAL AND METHODS: In this cross
      sectional study, repaired TOF patients who underwent CMR and echocardiography
      within a 4-week period between 2010 and 2011 at our Center were included. Linear
      regression was used to analyze degree of inter modality correlation. A prediction
      model tested the association between functional data/probrain natriuretic peptide
      (Pro-BNP) with CMR. RESULTS: Fifty patients were included in the study (mean age
      31 +/- 18 years). The best predictors of right ventricle (RV) ejection fraction
      at CMR were tricuspid anular plane systolic excursion (tricuspid valve anular
      plane systolic excursion, R 0.37, P < 0.0001) and RV peak S-wave velocity (R
      0.40, P < 0.001). Pro-BNP levels did present weak correlation with New York Heart
      Association functional class (R 0.31, P < 0.002) and QRS duration (R 0.32, P <
      0.002) and a moderate correlation with right atrium area at CMR (R 0.46, P <
      0.0001). CONCLUSION: We found limited correlation between the two imaging
      modalities in the evaluation of RV after intracardiac repair of TOF. Pro-BNP
      level presents moderate correlation with right atrium area measured with
      echocardiography. Serial CMR evaluations are needed in this patient population,
      but they may be interchanged by routine echocardiography in particular in
      patients with normal or stable echocardiographic parameters.

PMID- 30234685
TI  - Takotsubo cardiomyopathy: queries of the current era.
AB  - : Takotsubo cardiomyopathy (TTS), also known as left ventricular apical
      ballooning syndrome, is an acute, usually reversible heart failure syndrome that
      most often affects postmenopausal women experiencing an emotionally stressful
      event. It is characterized by sudden left ventricular dysfunction and wall motion
      abnormalities involving the apical and mid segments. TTS has been increasingly
      recognized in recent years, and more and more information about the
      pathophysiology, diagnosis, and treatment of these patients has been reported.
      However, much is still unknown. TTS has a wide variety of clinical subtypes and
      has been described in several clinical contexts. Moreover, TTS simulates ST
      segment elevation myocardial infarction and acute myocarditis, and it can be
      difficult to obtain a certain diagnosis. As a result, clinical decisions are
      challenging, and many patients currently receive an inappropriate management
      strategy. The aim of this review is to critically analyze the evidence about this
      disease reported in the literature, with particular focus on the
      pathophysiological processes, the diagnostic elements that can help the clinician
      differentiate it from other diseases, and the best management of these patients.

PMID- 30234686
TI  - Occupational and environmental exposure to polychlorinated biphenyls and risk of
      non-Hodgkin lymphoma: a systematic review and meta-analysis of epidemiology
      studies.
AB  - We carryied out a meta-analysis of studies on exposure to polychlorinated
      biphenyls (PCBs) and risk of non-Hodgkin lymphoma (NHL). Through a systematic
      search of the literature, we identified relative risks (RRs) for PCB exposure and
      NHL risk in 30 populations (10 occupational exposure, seven high environmental
      exposure, 13 without special exposure). We performed random effects meta-analyses
      for exposure to all PCBs, specific PCB congeners and risk of all NHL and NHL
      subtypes. The meta-RR for studies of occupational exposure, high environmental
      exposure, and no special exposure were 0.94 [95% confidence interval (CI): 0.84
      1.03], 1.05 (95% CI: 0.94-1.16), and 1.03 (95% CI: 0.72-1.34), respectively, and
      the cumulative meta-RR was 0.96 (95% CI: 0.85-1.07). No positive associations
      were found for exposure to specific congeners, nor for NHL subtypes. The meta-RR
      for an increase of 100 ppb serum or fat PCB level was 1.02 (95% CI: 1.00-1.04).
      There was weak indication of publication bias. Our meta-analysis found no
      association between PCB exposure and NHL risk, in particular in studies of
      occupational exposures. We detected a weak dose-response relation; the
      possibility of residual confounding and other sources of bias cannot be ruled
      out. PCBs are not likely to cause NHL in humans.

PMID- 30234687
TI  - 2015 Beers criteria medication review in assisted living facilities.
AB  - BACKGROUND AND PURPOSE: The elderly population is expected to double by 2050 with
      falls and hospitalizations due to adverse drug events having a major effect on
      health and quality of life. With the release of the revised 2015 American
      Geriatrics Society (AGS) Beers criteria, usage of potentially inappropriate
      medications (PIMs) should be studied to determine their effect on falls and
      hospitalizations in frail populations such as those in assisted living
      facilities. METHODS: This quality improvement project used a retrospective chart
      review on residents from a purposive sample of two assisted living facilities in
      Northern Virginia. Residents were aged >=65 and lived at the facility for at
      least 6 months and were not enrolled in hospice and/or palliative care or living
      in the dementia unit. The 2015 AGS Beers criteria were used to evaluate the
      effect of PIMs on falls and hospitalization rates. CONCLUSIONS: This project did
      not find statistical significance between PIMs and falls (p = .276). A favorable,
      but not statistically significant trend, was noted between PIMs and
      hospitalizations (p = .079). IMPLICATIONS FOR PRACTICE: Understanding the effect
      of PIMs on falls and hospitalizations could help providers improve prescribing
      practices for the elderly population who are at the greatest risk for potential
      adverse effects from polypharmacy.

PMID- 30234688
TI  - Role of contrast-enhanced 18F-FDG PET/CT imaging in the diagnosis and staging of
      renal tumors.
AB  - PURPOSE: The objectives of this prospective study are to compare intravenous
      contrast-enhanced (CE) fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed
      tomography (CE F-FDG PET/CT) with conventional methods (CT/MRI) and to evaluate
      the relationship of maximum standardized uptake value (SUVmax) with Fuhrman grade
      in patients with renal tumors. PATIENTS AND METHODS: A total of 62 patients [35
      males and 27 females; mean age 55.8+/-12.7 (range: 27-81) years] were enrolled in
      the study. CE F-FDG PET/CT scanning included whole-body (early) and abdominal
      imaging (late) 1 and 2 h after intravenous F-FDG administration, respectively.
      SUVmax was calculated for primary tumors. CE F-FDG PET/CT and CT/MRI findings
      were compared with respect to primary tumors and staging. RESULTS: The
      sensitivity of CE F-FDG PET/CT in primary tumor detection was 98%, which was very
      close to that of CT/MRI (100%). CE F-FDG PET/CT resulted in correct staging in
      84% of the cases, compared with 68% of the cases with conventional methods (52
      vs. 42 patients). SUVmax values of early PET for the primary tumors were
      significantly correlated with the Fuhrman grades (P<0.001). CE F-FDG PET/CT
      enabled the detection of synchronous tumors in four patients, one of which was
      incorrectly diagnosed as having metastasis by CT. Distant metastases were
      detected in 16 patients with CE F-FDG PET/CT and in 13 patients with routine
      conventional methods. CONCLUSION: CE F-FDG PET/CT showed similar results compared
      with CT/MRI in the detection of primary tumors, but it was superior to
      conventional methods in the detection of metastasis and staging. Given the highly
      significant correlation between SUVmax values and the Fuhrman grading, CE F-FDG
      PET/CT may play a significant role in the evaluation of patient prognosis.

PMID- 30234689
TI  - The feasibility of using 18F-FDG-PET/CT in patients with mucinous breast
      carcinoma.
AB  - PURPOSE: This study investigated the correlation between fluorine-18
      fluorodeoxyglucose (F-FDG)-PET/computed tomography (CT) and clinicopathological
      factors in patients with mucinous breast carcinoma and assessed the feasibility
      of using F-FDG-PET/CT in evaluating tumors. PATIENTS AND METHODS: We
      retrospectively examined 42 consecutive patients with pathologically proven
      mucinous breast carcinoma who preoperatively underwent F-FDG-PET/CT. In addition,
      we compared F-FDG uptake with clinicopathological characteristics. RESULTS: F-FDG
      uptake was observed in 39 (92.9%) lesions. The maximum standardized uptake value
      (SUVmax) (mean+/-SD) of all mucinous carcinoma, pure type, and mixed type was
      2.3+/-1.3 (range: 1.0-5.1), 1.9+/-0.9 (range: 1.0-3.5), and 3.2+/-1.3 (range: 1.4
      5.1), respectively. The mixed type had a significantly higher F-FDG uptake than
      the pure type (P=0.006). In addition, the sensitivity, specificity, accuracy, and
      area under the curve for distinguishing the pure type from the mixed type were
      61.5, 89.7, 81.0, and 0.76, respectively (cutoff value: SUVmax>3.0). Furthermore,
      SUVmax correlated significantly with the high nuclear grade (P=0.010) and the
      presence of axillary lymph node metastasis (P=0.017). CONCLUSION: F-FDG uptake
      efficiently distinguishes the pure type from the mixed type and may play a
      potential role in predicting the aggressiveness of mucinous breast carcinoma.

PMID- 30234690
TI  - Relative Yield of MEG and EEG Spikes in Simultaneous Recordings.
AB  - PURPOSE: Most clinical magnetoencephalography (MEG) centers record both MEG and
      EEG, but model only MEG sources. This may be related to the belief that MEG
      spikes are more prevalent, MEG is more sensitive, or to proprietary software
      limitations. Biophysics would contend, however, that EEG, being sensitive to
      radial and tangential source orientations, would provide complementary data for
      analysis. METHODS: We recorded 306 channels of MEG and 25 channels of EEG
      simultaneously in 297 consecutive patients over 3 years. We inspected the MEG and
      EEG recordings separately, identified spikes in both, determined whether their
      voltage and/or magnetometer magnetic fields were dipolar and thus model-worthy,
      and segregated them into types based on similar and distinct field topography. We
      placed for each patient their spike types into categories, including those with
      both a recognizable MEG and EEG signal and those with only an MEG and only an EEG
      signal. RESULTS: Eighty-three percent of patients had spikes recorded, and these
      patients had an average of 2.7 spike types each. Fifty-six percent of spike types
      were present in both MEG and EEG. However, 36% of spike types were only evident
      in EEG, whereas 8% were noted in MEG alone. In 49% of patients with spikes, MEG
      review missed at least one spike type, whereas in 17% of patients, EEG review
      missed at least one spike type. CONCLUSIONS: To obtain an optimal yield of
      diagnostic information, EEG should also be subjected to source analysis in any
      clinical MEG study. EEG and MEG data are indeed complementary.

PMID- 30234691
TI  - Effect of Probe-Tone Frequency on Ipsilateral and Contralateral Electrical
      Stapedius Reflex Measurement in Children With Cochlear Implants.
AB  - OBJECTIVES: The upper loudness limit of electrical stimulation in cochlear
      implant patients is sometimes set using electrically elicited stapedius reflex
      thresholds (eSRTs), especially in children for whom reporting skills may be
      limited. In unilateral cochlear implant patients, eSRT levels are measured
      typically in the contralateral unimplanted ear because the ability to measure
      eSRTs in the implanted ear is likely to be limited due to the cochlear implant
      surgery and consequential changes in middle ear dynamics. This practice is
      particularly limiting in the case of fitting bilaterally implanted pediatric
      cases because there is no unimplanted ear option to choose for eSRT measurement.
      The goal of this study was to identify an improved measurement protocol to
      increase the success of eSRT measurement in ipsilateral or contralateral or both
      implanted ears of pediatric cochlear implant recipients. This work hypothesizes
      that use of a higher probe frequency (e.g., 1000 Hz compared with the 226 Hz
      standard), which is closer to the mechanical middle ear resonant frequency, may
      be more effective in measuring middle ear muscle contraction in either ear.
      DESIGN: In the present study, eSRTs were measured using multiple probe
      frequencies (226, 678, and 1000 Hz) in the ipsilateral and contralateral ears of
      19 children with unilateral Advanced Bionics (AB) cochlear implants (mean age =
      8.6 years, SD = 2.29). An integrated middle ear analyzer designed by AB was used
      to elicit and detect stapedius reflexes and assign eSRT levels. In the integrated
      middle ear analyzer system, an Interacoustics Titan middle ear analyzer was used
      to perform middle ear measurements in synchrony with research software running on
      an AB Neptune speech processor, which controlled the delivery of electrical pulse
      trains at varying levels to the test subject. Changes in middle ear acoustic
      admittance following an electrical pulse train stimulus indicated the occurrence
      of an electrically elicited stapedius reflex. RESULTS: Of the 19 ears tested,
      ipsilateral eSRTs were successfully measured in 3 (16%), 4 (21%), and 7 (37%)
      ears using probe tones of 226, 678, and 1000 Hz, respectively. Contralateral eSRT
      levels were measured in 11 (58%), 13 (68%), and 13 (68%) ears using the three
      different probe frequencies, respectively. A significant difference was found in
      the incidence of successful eSRT measurement as a function of probe frequency in
      the ipsilateral ears with the greatest pair-wise difference between the 226 and
      1000 Hz probe. A significant increase in contralateral eSRT measurement success
      as a function of probe frequency was not found. These findings are consistent
      with the idea that changes in middle ear mechanics, secondary to cochlear implant
      surgery, may interfere with the detection of stapedius muscle contraction in the
      ipsilateral middle ear. The best logistic, mixed-effects model of the occurrence
      of successful eSRT measures included ear of measurement and probe frequency as
      significant fixed effects. No significant differences in average eSRT levels were
      observed across ipsilateral and contralateral measurements or as a function of
      probe frequency. CONCLUSION: Typically, measurement of stapedius reflexes is less
      successful in the implanted ears of cochlear implant recipients compared with
      measurements in the contralateral, unimplanted ear. The ability to measure eSRT
      levels ipsilaterally can be improved by using a higher probe frequency.

PMID- 30234692
TI  - Comparing Outcomes of Active Student and Observer Roles in Nursing Simulation.
AB  - BACKGROUND: Because of large class sizes and limited resources, students
      participating in high-fidelity simulation experiences may be assigned to an
      observer role as opposed to an active nursing role. PURPOSE: Educators need to
      determine if anxiety levels and student learning outcomes are comparable for
      students in active and observer roles. METHODS: A quasi-experimental study was
      conducted with 132 prelicensure baccalaureate students. Active nursing roles
      consisted of primary care, documentation, and medication nurse roles. Observer
      role students were provided with resources to guide them with developing their
      observational skills and achieving the simulation objectives. RESULTS: There were
      no significant differences between simulation roles for anxiety levels,
      satisfaction with learning, self-confidence in learning, clinical ability,
      problem solving, confidence in clinical practice, and collaboration. CONCLUSIONS:
      These findings suggest that either role is an appropriate assignment during
      simulation. Educators should identify ways to be supportive and reduce anxiety in
      students during simulation experiences.

PMID- 30234693
TI  - Measuring Decrement in Change-of-Direction Speed Across Repeated Sprints in
      Basketball: Novel vs. Traditional Approaches.
AB  - Scanlan, AT, Madueno, MC, Guy, JH, Giamarelos, K, Spiteri, T, and Dalbo, VJ.
      Measuring decrement in change-of-direction speed across repeated sprints in
      basketball: Novel vs. traditional approaches. J Strength Cond Res XX(X): 000-000,
      2018-Approaches to quantify decrement in change-of-direction speed during
      repeated sprints in basketball players have traditionally used total performance
      time, which is strongly influenced by linear speed. The purpose of this study was
      to compare performance decrement across change-of-direction sprints using total
      performance time and a novel approach that better isolates change-of-direction
      speed, termed change-of-direction deficit (CODD). Semiprofessional basketball
      players (N = 8; 19.9 +/- 1.5 years; 183.0 +/- 9.6 cm; 77.7 +/- 16.9 kg) completed
      12 * 20-m change-of-direction sprints (Agility 5-0-5 trials) with 20-second
      recoveries between each sprint. Agility 5-0-5 performance time was taken as the
      duration to cover 5 m immediately before and after (10 m in total) a 180 degrees 
      directional change. Change-of-direction deficit was calculated as the difference
      between mean 10- and 20-m split time determined during reference 20-m linear
      sprints in a separate session and Agility 5-0-5 time in each sprint. Performance
      decrement was calculated for each approach as: ([total time/ideal time] * 100) -
      100. Comparisons between approaches were made using a paired-sample t-test,
      effect size analyses, and magnitude-based inferences. A significantly greater (P
      < 0.001; effect size = 2.16, very large; almost certainly higher) performance
      decrement was apparent using CODD (5.99 +/- 1.88%) than Agility 5-0-5 performance
      time (2.84 +/- 0.84%). The present findings indicate that change-of-direction
      speed measured with CODD shows promise in providing different insight and
      deteriorates more than total performance time during repeated sprints in
      basketball players. Change-of-direction deficit has potential to better isolate
      decrements in change-of-direction speed across repeated sprints compared with
      total performance time.

PMID- 30234694
TI  - Changes in Energy Expenditure, Dietary Intake, and Energy Availability Across an
      Entire Collegiate Women's Basketball Season.
AB  - Zanders, BR, Currier, BS, Harty, PS, Zabriskie, HA, Smith, CR, Stecker, RA,
      Richmond, SR, Jagim, AR, and Kerksick, CM. Changes in energy expenditure, dietary
      intake, and energy availability across an entire collegiate women's basketball
      season. J Strength Cond Res XX(X): 000-000, 2018-The purpose of this study was to
      identify changes in energy expenditure and dietary intake across an entire
      women's basketball season. On 5 different occasions across the competitive
      season, female collegiate basketball players (19.8 +/- 1.3 years, 173.9 +/- 13.6
      cm, 74.6 +/- 9.1 kg, 27.1 +/- 3.2% fat, 53.9 +/- 6.4 ml.kg.min, n = 13) were
      outfitted with heart rate and activity monitors over 4 consecutive days and
      completed 4-day food and fluid records to assess changes in energy expenditure
      and dietary status. Dual-energy x-ray absorptiometry was used to assess baseline
      body composition and resting energy expenditure (REE) was measured before and
      after the season. Data were analyzed using 1-factor repeated-measures analysis of
      variance. Total daily energy expenditure (TDEE, p = 0.059) and physical activity
      levels (TDEE/REE, p = 0.060) both tended to decrease throughout the season.
      Energy balance was negative at all time points throughout the season. Absolute
      and normalized daily protein intake at the end of the season was significantly (p
      < 0.05) lower than at the beginning of the season. Carbohydrate (3.7 +/- 0.4
      g.kg.d) and protein (1.17 +/- 0.16 g.kg.d) intakes were lower than commonly
      recommended values based on previously published guidelines. These findings
      suggest that greater education and interventions for collegiate athletes and
      coaches regarding dietary intake and energy expenditure are warranted.

PMID- 30234695
TI  - Muscle Activation During Power-Oriented Resistance Training: Continuous vs.
      Cluster Set Configurations.
AB  - Morales-Artacho, AJ, Garcia-Ramos, A, Perez-Castilla, A, Padial, P, Gomez, AM,
      Peinado, AM, Perez-Cordoba, JL, and Feriche, B. Muscle activation during power
      oriented resistance training: continuous vs. cluster set configurations. J
      Strength Cond Res XX(X): 000-000, 2018-This study examined performance and
      electromyography (EMG) changes during a power training protocol comprising
      continuous or clustered set configurations. Eighteen active males completed 6
      sets of 6 repetitions during the loaded (20% 1 repetition maximum)
      countermovement jump (CMJ) exercise, continuously (n = 9) or with a 30-second
      pause every 2 repetitions (cluster; n = 9). Power output, vastus lateralis (VL),
      vastus medialis (VM), and rectus femoris (RF) EMG were recorded during all CMJs.
      Relative changes from the first repetition were assessed on the EMG root mean
      square (RMS), median frequency (Fmed), and a low- to high-frequency ratio index
      of fatigue (FInsmk). Greater power output decrements were observed during the
      continuous set configuration (p = 0.001, eta G < 0.01). Greater RMS increments in
      VL (6.8 +/- 11.3 vs. -1.7 +/- 5.8%) and RF (9.3 +/- 14.2 vs. 1.9 +/- 6.9%), but
      not VM (2.0 +/- 4.7 vs. 2.6 +/- 7.3%), were also observed in the continuous
      compared with the cluster sets (p = 0.033, eta G = 0.06). Progressive decrements
      in Fmed and increments in FInsmk were observed across repetitions in both set
      configurations. In conclusion, although clustering sets between repetitions
      clearly maintained power output, mixed responses were observed on the examined
      EMG parameters.

PMID- 30234697
TI  - The prevalence and years lived with disability caused by low back pain in China,
      1990 to 2016: findings from the global burden of disease study 2016.
AB  - The aim of this work was to quantify the prevalence and years lived with
      disability (YLDs) caused by low back pain (LBP) in China from 1990 to 2016. Data
      from the GBD 2016 (Global Burden of Diseases, Injuries, and Risk Factors Study
      2016) were used. We analyzed the age-sex-province-specific prevalence and YLDs
      for LBP of 33 provinces/regions in China. Comparisons were made with the data
      retrieved from the 1990 GBD study. We estimated that 5.45 * 10 individuals had
      LBP in 1990, which rose to 6.73 * 10 in 2016. The age-standardized prevalence of
      LBP decreased from 5.6% (95% uncertainty interval [95% UI]: 4.9%-6.3%) in 1990 to
      4.2% (95% UI: 3.8%-4.8%) in 2016. The YLDs for LBP increased from 6.2 million
      (95% UI: 4.3-8.3 million) in 1990 to 7.7 million (95% UI: 5.4-10.2) in 2016. Age
      standardized YLD rate (per 100,000 person) decreased from 637.5 (95% UI: 449.9
      848.8) in 1990 to 481.9 (95% UI: 338.6-637.0) in 2016. A female preponderance was
      observed for prevalence and YLDs. The prevalence and YLDs rate for LBP slightly
      decreased from 1990 to 2016 in China; however, the total individuals and YLDs
      increased. Low back pain still ranks as the second leading cause of YLD burden
      disease in China. Considerable attention should be paid for LBP, especially in
      the female population.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.

PMID- 30234698
TI  - Why do some people develop chronic, treatment-resistant pain and not others?

PMID- 30234699
TI  - What makes surgical nerve injury painful? A 4-year to 9-year follow-up of
      patients with intercostobrachial nerve resection in women treated for breast
      cancer.
AB  - Nerve injury during breast cancer surgery can cause neuropathic pain (NP). It is
      not known why some, but not all, patients develop chronic postsurgical
      neuropathic pain (CPSNP) after the same nerve injury. In this study, we examined
      251 breast cancer survivors with surgeon-verified intercostobrachial nerve
      resection to identify factors that associate with CPSNP. The patients were
      recruited from a previous study of 1000 women treated for breast cancer in 2006
      to 2010. This enabled us to analyze preoperative factors that associate with
      future CPSNP. The patients were re-examined in 2014 to 2016 to diagnose CPSNP
      using the revised NP diagnostic criteria. Preoperative assessments were pain in
      the area to be operated on, any chronic pain condition, depressive symptoms,
      anxiety, sleep, and experimental cold pain sensitivity using the cold pressor
      test (CPT). Follow-up assessments were CPT, psychological factors, sleep, any
      chronic pain, and basic laboratory tests. One hundred thirty-seven (55%) patients
      with intercostobrachial nerve resection fulfilled CPSNP diagnostic criteria after
      4 to 9 years. Of them, 30 patients (22%) had moderate to severe pain in self
      reports and 86 (63%) presented moderate to severe evoked pain at examination.
      Preoperative pain in the surgical area, other chronic pains, and breast
      conserving surgery were associated with future CPSNP. Other chronic pains,
      increased psychological burden, and insomnia, both before surgery and at the
      follow-up, were associated with CPSNP. Preoperative CPT did not associate with
      future CPSNP. Patients with established CPSNP showed increased pain sensitivity
      in CPT and higher levels of inflammatory markers, suggesting that central
      sensitization and inflammation may associate with the maintenance of CPSNP.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.

PMID- 30234700
TI  - The long-term outcomes of posteromedial limited surgery for developmental
      dysplasia of the hip: a mean 17.3-year follow-up.
AB  - The objectives of this retrospective study were to evaluate long-term functional
      and radiological outcomes of 102 dislocated hips of 79 patients treated with the
      modified medial approach and to compare them with respect to both of our short
      term and mid-term outcomes and also with the current literature. The mean age at
      operation was 11.3+/-4.3 months (range: 3-18 months), with a minimum follow-up of
      15 years (range: 15-23 years). It was determined that 94.1% of mean hip scores
      were either good or excellent. Avascular necrosis, subluxation/redislocation, and
      secondary surgeries were 14.8, 6.9, and 7.8%, respectively. We believe this
      modified procedure requiring no routine arthrotomy is safe and effective.

PMID- 30234701
TI  - Pediatric obesity is associated with short-term risks after pelvic osteotomy.
AB  - The risk factors for increased perioperative morbidity following pediatric pelvic
      osteotomies are poorly understood. The purpose of this study was to characterize
      differences in adverse events, operative time, length of stay, and readmission
      following pelvic osteotomy for obese and nonobese patients. A retrospective
      cohort study was carried out using the National Surgical Quality Improvement
      Program Pediatric database to identify patients that underwent pelvic osteotomy
      with or without femoral osteotomy. Obesity was found to be an independent risk
      factor for blood transfusion (relative risk: 1.4, P=0.007) and readmission
      (relative risk: 2.3, P=0.032) within 30 days. These data can facilitate patient
      counseling and informed decision-making when planning for surgical correction of
      hip dysplasia.

PMID- 30234702
TI  - Transient Elastography Measurements of Spleen Stiffness as a Predictor of
      Clinically Significant Varices in Children.
AB  - OBJECTIVES: Investigate the use of spleen stiffness measurements (SSMs), measured
      by transient elastography (TE), for the prediction of clinically significant
      varices (CSV) in children with portal hypertension. METHODS: This observational
      cohort study included children selected for endoscopy, as per department
      protocol, between September 2015 and June 2016. Those included underwent single
      TE FibroScan for liver stiffness measurements and SSM. Clinical and laboratory
      data were collected and variceal prediction scores were calculated at time of
      elastography. RESULTS: In total 67 children (32 boys) underwent TE. Fifty-two
      children (25 boys) had chronic liver disease (CLD), 15 (7 boys) portal vein
      thrombosis (PVT). In all children SSM was the best predictor of CSV+ve, with an
      optimal cut-off value of 38.0 kPa (area under the receiver operator curve [AUROC]
      = 0.92, sensitivity = 89%, specificity = 82%, P < 0.01). In the CLD group SSM was
      also the best predictor, with an optimal cut-off value of 38.05 kPa (AUROC =
      0.90, sensitivity = 84%, specificity = 87%, P < 0.01). In the PVT group only SSM
      was predictive of CSV+ve, with an optimal cut-off value of 16.8 kPa (AUROC =
      1.00, sensitivity = 100%, specificity = 100%, P < 0.001). For the prediction of
      GI bleeding (n = 6), liver stiffness measurement performed the best, with an
      optimal cut-off value of 34.3 kPa (AUROC = 0.84, sensitivity of 80%, specificity
      of 88%, P = 0.01). CONCLUSIONS: SSM was the greatest predictor of CSV+ve in the
      whole cohort, and individual CLD and PVT groups. SSM could be used as a
      noninvasive screening tool for children with portal hypertension to stratify the
      risk of having CSV.

PMID- 30234703
TI  - Factors Influencing Nurses' Perceptions of the Baccalaureate Degree in Nursing as
      Minimum Requirement for Professional Practice.
AB  - AIM: The purpose of this study was to determine factors influencing nurses'
      perceptions of the baccalaureate degree in nursing as the minimum requirement for
      professional practice. BACKGROUND: The associate degree nursing program was
      created in response to a nursing shortage in the early 1950s. In 1965, the
      American Nurses Association recommended that the BSN be the minimum to practice
      professionally as a nurse. METHOD: A quantitative method with a descriptive
      design was used. An online, Likert-type survey collected data from 61 nurses in
      southern Michigan and northern Indiana. Two open-ended questions were included to
      gain perceptions in nurses' own words. RESULTS: Higher education was noted as
      positive for nurses, but not necessary for becoming an expert nurse. The most
      common factors influencing advancing education were time and money, followed by
      career advancement. CONCLUSION: The study supports the idea that if nurses are
      able, they will continue their education.

PMID- 30234704
TI  - A Young Man with Trisomy 21 and Sudden Behavioral Changes.
AB  - CASE: Grant is a 13-year-old boy with trisomy 21 who presents with his mother for
      concerns regarding the emergence of several new disruptive behaviors. While he is
      verbal, he also communicates through an augmentative communication device. He
      currently attends a residential school. Over the past 2 months, he has begun
      spitting at the staff, engaging in self-injurious behaviors, placing his hands in
      his pants, and frequently talking about "pee and poop." Notably, Grant has
      undergone several changes to his educational placement and medical health over
      the past several months. He recently transferred to his current residential
      school from another placement to be closer to his family, although this has meant
      that Grant was unable to work with his long-time aide. Additionally, most of the
      students at Grant's current school are significantly lower functioning than him,
      such that Grant is one of the few verbal children.Approximately 3 months ago,
      Grant underwent significant dental work under anesthesia. Grant had previously
      taken an alpha-agonist for behavioral management, although he was weaned off this
      4 months ago because of increasing somnolence increasing somnolence. Grant's
      recent behavioral challenges make performing community and home activities more
      challenging.Grant's behavioral history is notable for a previous episode of
      behavioral and emotional challenges 18 months ago. This occurred in the setting
      of transitioning to a new classroom with higher academic and behavioral
      expectations and decreased time spent with his family. These behaviors had
      consisted of self-injurious behaviors and tantrums consisting of crying and
      social withdrawal. This was managed by increased behavioral and academic supports
      via trained teachers and aides, medication management, and optimizing his
      augmentative communication. After these interventions, Grant's behavioral and
      emotional functioning improved and remained stable until this current
      episode.Grant's mother is concerned about what may be causing these emerging
      behaviors and wondering if any of the recent educational and medical stressors
      could be contributing. What do you do next?

PMID- 30234705
TI  - Financial Analysis of Closed Femur Fractures in 3- to 6-Year-Olds Treated With
      Immediate Spica Casting Versus Intramedullary Fixation.
AB  - BACKGROUND: Health care in America continues to place more importance on
      providing value-based medicine. Medicare reimbursements are increasingly being
      tied to this and future policy changes are expected to reinforce these trends.
      Recent literature has shown pediatric femur fractures in preschool-age children
      have equivalent clinical and radiographic outcomes when treated with spica
      casting or flexible intramedullary nails (IMN). We compared hospital care
      statistics including charges for nonoperative versus operative treatment for
      closed femur fractures in 3- to 6-year-olds. METHODS: An IRB-approved
      retrospective chart review was performed of 73 consecutive 3- to 6-year-olds
      treated at a regional level 1 pediatric hospital from January 1, 2009 to December
      31, 2013 with an isolated, closed femoral shaft fracture. Exclusion criteria
      included open fractures, bilateral injury, and polytrauma. Immediate spica
      casting was performed in the Emergency Department or Anesthesia Procedure Unit
      versus IMN in the operating room. RESULTS: A total of 41 patients were treated
      with spica casting and 32 patients were treated operatively with flexible IMNs; 3
      patients failed nonoperative care. After analysis of final treatment groups,
      significant differences included age at injury: 3.7 years for cast versus 5.3
      years for IMN (P<0.001), time to discharge 21 versus 41 hours (P<0.001), 3.2
      versus 4.4 clinic visits (P<0.001), follow-up 3.5 versus 9.4 months (P<0.001).
      Orthopedic surgeon charges were $1500 for casted patients versus $5500 for IMN
      (P<0.001). Total hospital charges were $19,200 for cast versus $59,700 for IMN
      (P<0.001). No difference was found between clinic charges or number of
      radiographs between groups. In total, 76% of cast group were discharged <24 hours
      from admission versus 8.6% in operative group. In the operative group, 83% had
      implant removal with no statistically significant charge difference between those
      who had implant removal versus retention. CONCLUSIONS: Treatment of pediatric
      femur fractures in 3- to 6-year-olds with IMN is associated with longer hospital
      stays, significantly greater hospital charges, longer follow-up and more clinic
      visits compared with spica casting. These findings are at odds with previous
      literature showing shorter hospital stays and decreased cost with nailing
      compared to traction and casting. This shows a clear difference between 2
      treatments that yield similar clinical and radiographic outcomes. LEVEL OF
      EVIDENCE: Level III-retrospective comparative study.

PMID- 30234706
TI  - Reconstruction of Temporal Bone Defect Using a Vertically-Oriented Free Muscle
      Sparing Rectus Abdominis Musculocutaneous Flap.
AB  - Reconstruction of a temporal bone defect after tumor ablation should provide
      watertight filling and adequate resurfacing. A muscle-sparing rectus abdominis
      musculocutaneous (ms-RAMC) flap with de-epithelized skin paddle has been used and
      early experience was reported. Case series enrolled 7 patients who underwent free
      ms-RAMC flap after tumor ablation for external auditory canal cancer. Vertically
      oriented flap was harvested with central strip of muscle. Distal skin paddle was
      de-epithelized to fill the bony defect. Immediate facial nerve reconstruction was
      performed whenever indicated. The average operation time for reconstruction was
      280 minutes. No early complication was reported. An ms-RAMC flap with de
      epithelized skin paddle can be used for temporal bone defect reconstruction with
      its anatomic consistency and technical simplicity. It can provide sufficient bulk
      for water tight packing that lasts after irradiation. The 11th intercostal nerve
      can be harvested during pedicle dissection. Muscle sparing technique could
      minimize donor-site morbidity.

PMID- 30234707
TI  - The SOBRAPAR Hospital Craniofacial Surgery Fellowship: Wide Craniofacial Surgery
      Training Based on Historical and Evolving Principles.

PMID- 30234708
TI  - Necrosis of the Glabella After Injection With Hyaluronic Acid Into the Forehead.
AB  - Skin necrosis is a rare but severe potential complication after injection of
      hyaluronic acid (HA). Based on the understanding of the causes and mechanisms of
      this complication, many precautions have been proposed. Still, this adverse
      reaction happened from time to time. Here, the authors present a patient with
      glabellar skin necrosis following an injection into the forehead using HA filler.
      Although not uncommon, this patient might suggest an alternative cause or
      mechanism of tissue necrosis following HA injection besides intravascular
      injection or extravascular compression directly by HA filler. Further study is
      needed to examine other possible causes in order to eliminate this risk.

PMID- 30234709
TI  - Upper Eyelid Approach for the Reconstruction of Isolated Fractures of the
      Anterior Wall of the Frontal Sinus.
AB  - The management of frontal sinus fractures can vary widely depending on
      involvement of the anterior wall, the posterior wall, and the frontonasal duct.
      The main morbidity associated with isolated anterior wall fractures is an
      aesthetic deformity. Treatment includes coronal, endoscopic, and transcutaneous
      approaches. However, each has reported limitations and associated risks of
      iatrogenic injuries. In this paper, the authors discuss a novel approach through
      the upper eyelid crease and examine 4 cases where it is utilized for anterior
      frontal sinus wall, superior orbital rim, and orbital roof fracture repair.

PMID- 30234696
TI  - When pain gets stuck: the evolution of pain chronification and treatment
      resistance.
AB  - It is well-recognized that, despite similar pain characteristics, some people
      with chronic pain recover, whereas others do not. In this review, we discuss
      possible contributions and interactions of biological, social, and psychological
      perturbations that underlie the evolution of treatment-resistant chronic pain.
      Behavior and brain are intimately implicated in the production and maintenance of
      perception. Our understandings of potential mechanisms that produce or exacerbate
      persistent pain remain relatively unclear. We provide an overview of these
      interactions and how differences in relative contribution of dimensions such as
      stress, age, genetics, environment, and immune responsivity may produce different
      risk profiles for disease development, pain severity, and chronicity. We propose
      the concept of "stickiness" as a soubriquet for capturing the multiple influences
      on the persistence of pain and pain behavior, and their stubborn resistance to
      therapeutic intervention. We then focus on the neurobiology of reward and
      aversion to address how alterations in synaptic complexity, neural networks, and
      systems (eg, opioidergic and dopaminergic) may contribute to pain stickiness.
      Finally, we propose an integration of the neurobiological with what is known
      about environmental and social demands on pain behavior and explore treatment
      approaches based on the nature of the individual's vulnerability to or protection
      from allostatic load.

PMID- 30234710
TI  - A New Proposal for Three-Dimensional Positioning of the Chin Using a Single
      Computer-Aided Design/Computer-Aided Manufacturing Surgical Guide.
AB  - The workflow digital to aid the treatment of dentofacial deformities is a
      reality. Associated with the virtual planning, the creation of surgical guides
      assists the performance of osteotomies and bone positioning, increasing the
      accuracy of surgical outcomes. This study aims to present a new method of
      surgical guide for genioplasty based on the selected osteosynthesis plate.

PMID- 30234711
TI  - Complex Orbital Fractures: Three-Dimensional Planning and Combined Surgical
      Approach.
AB  - Nowadays the development of diagnostic imaging, surgical techniques, alloplastic
      materials, and surgical instruments has made possible a more accurate management
      of orbital fractures. The aim of the present study was the management of orbital
      fractures and the solution of particular cases. The use of high-resolution
      computed tomography makes possible to gain a better understanding of the complex
      orbit anatomical structure. Also endoscopy is a valid alternative for medial
      orbital wall fractures treatment. It gives high control of the fracture site and
      its reduction. When this technology is combined with 3-dimensional (3D)
      reformatted images, it allows us to reconstruct more accurately the orbital
      defects. The authors present their experience in complex orbital fractures
      treated with the aim of the 3D navigation using a preformed orbital titanium
      plate. Endosopical approach was used to control plate positioning.

PMID- 30234713
TI  - Nasal Tip Grafts.
AB  - OBJECTIVES: The nasal tip is the most prominent part of the nose. The aim of this
      paper is to review nasal tip grafts with detailed explanation and figures.
      METHODS: The authors searched PubMed, Google, Google Scholar, and Proquest
      Central database of the Kirikkale University. Search was performed with the key
      words of "nasal," "tip," "graft." The indications and grafting techniques were
      presented. RESULTS: The external shape of the nasal tip is determined by the
      curves and contours of the lower lateral cartilages and their interactions with
      the surrounding tissues. Normative data exist regarding the ideal shape and
      shadowing of the nasal tip. The mainly used tip grafts in rhinoplasty are
      "Floating graft (Goldman) ," "Tip Onlay Graft," "Columellar Strut Graft," "Caudal
      Septal Extension Graft," "Shield Graft," "Alar batten onlay graft," "Lateral
      Crural Strut Grafts," "Alar rim grafts." CONCLUSION: When tip sutures are not
      enough, cartilage tip grafts offer a versitile and effective way to change the
      nasal tip. While there has been a vast array of grafting techniques described,
      this paper reviewed many of the most popular and useful grafts in modern use.

PMID- 30234712
TI  - The Promising Effects of Transplanted Umbilical Cord Mesenchymal Stem Cells on
      the Treatment in Traumatic Brain Injury.
AB  - Many studies have reported the recovery ability of umbilical cord-derived
      mesenchymal stem cells (UC-MSCs) for neural diseases. In this study, the authors
      explored the roles of UC-MSCs to treat the traumatic brain injury. Umbilical cord
      derived mesenchymal stem cells were isolated from healthy neonatal rat umbilical
      cord immediately after delivery. The traumatic brain injury (TBI) model was
      formed by the classical gravity method. The authors detected the behavior changes
      and measured the levels of inflammatory factors, such as interleukin-lbeta and
      tumor necrosis factor-alpha by enzyme linked immunosorbent assay (ELISA) at 1, 2,
      3, 4 weeks after transplantation between TBI treated and untreated with UC-MSCs.
      Simultaneously, the expression of glial cell line-derived neurotrophic factor
      (GDNF) and brain derived neurotrophic factor (BDNF) were measured by real-time
      polymerase chain reaction and ELISA.The authors found that the group of
      transplantation UC-MSCs has a significant improvement than other group treated by
      phosphate buffered saline. In the behavioral test, the Neurological Severity
      Scores of UC-MSCs + TBI group were lower than TBI group (P < 0.05), but not
      obviously higher than control group at 2, 3, and 4week, respectively. The
      inflammatory factors are significantly reduced comparison with TBI group (P <
      0.05), but both GDNF and BDNF were higher than TBI group (P < 0.05). The results
      indicated that UC-MSCs might play an important role in TBI recovery through
      inhibiting the release of inflammatory factors and increasing the expression of
      GDNF and BDNF.

PMID- 30234714
TI  - Correlation Between the Existing Classifications of Nasal Bone Fractures and
      Subjective Patient Satisfaction.
AB  - Since the nose is at the center of the face, small changes to it can cause a big
      overall change. Therefore, a nasal fracture needs to be operated on when
      deformity is expected. Although many taxonomies have been developed for nasal
      bone fractures, no study has aimed to predict individual patient satisfaction.
      Herein, the authors tried to determine any correlation between the existing
      classifications of nasal bone fractures and subjective patient satisfaction. A
      retrospective study and telephone survey were conducted in 149 patients who
      underwent closed reduction for a pure nasal bone fracture. Pretraumatic,
      prereduction, and postoperative patient satisfactions were measured on a
      numerical scale from 1 to 5. The difference between pretraumatic and prereduction
      satisfactions was calculated to confirm the change in short-term satisfaction
      after trauma. The difference between pretraumatic and preoperative satisfactions
      was measured to determine change in long-term satisfaction postoperatively. The
      Stranc Robertson classification, modified Murray classification, and the presence
      of septal fracture were used to classify fractures. Independent and Jonckheere
      Terpstra t tests were used in statistical analysis. Only 86 of 149 were included
      in the study. There was no significant difference in patient satisfaction among
      frontal/lateral (P = 0.70, 0.56), frontal I/II (P = 1.00, 0.24), and lateral I/II
      groups (P = 0.57, 0.67) according to the Stranc Robertson classification. Septal
      fracture (P = 0.21, 0.44) and the modified Murray classification (P = 0.14, 0.47)
      also had no effect on satisfaction. Existing classification systems have the
      advantage of reflecting and distinguishing the characteristics of fractures, but
      there is a limit in their ability to reflect subjective patient satisfaction.

PMID- 30234715
TI  - Should You Buy a Three-Dimensional Printer? A Study of an Orbital Fracture.
AB  - The use of three-dimensional (3D) printing has been growing significantly in
      medicine for the past 10 years, especially in maxillofacial surgery. A lot a
      different softwares and printers are available on the market, and it can be
      difficult to choose which one fits best one's needs. In the authors' institution,
      the authors regularly print orbits to prepare the reconstruction. The authors
      then compared the 3D printing of an orbital fracture between a professional and
      nonprofessional software and between a bottom of the range and a more elaborated
      printer. The results show that there is a wide variation between the quality of
      the printing, as well as the time used for the preparation. Costs between free or
      professional software must also be considered. In conclusion, an analysis of
      needs and what is available on the market must be studied before investing in 3D
      printing.

PMID- 30234716
TI  - Normative Data of the Interorbital Distance in Thai Population.
AB  - The incidence of the patients with craniofacial anomalies was high in southeast
      Asian countries, for example, fronto-ethmoidal encephalo-menigocele or
      craniosynostosis. These craniofacial anomalies usually involve orbits, so a
      surgical orbital reconstruction is always required.Various methods have been used
      in the past to indirectly analyze the craniofacial region. Plain skull
      radiography, anthropometry, and cephalometry provided the limited information of
      interorbital distance in terms of accuracy whereas the interorbital distance is
      crucial to be reconstructed, increasing or decreasing. The accurate normal
      interorbital distance which grows by age as other craniofacial structures is the
      important data in the part of interorbital and orbital reconstruction. To date,
      the normative data of the bony interorbital distance among Thai population have
      not been established.The purpose of this study is to provide normal values and
      the growth patterns of the bony interorbital distances and other dimensions of
      the orbit according to age among Thai population through the axial computed
      tomography. Comparisons can then be made between normal values and those for an
      individual patient or those for a group of patients, for example, those with
      front-ethmoidal meningoencephalocele, Crouzon, or Treacher-Collins syndrome, or
      among values for individual patients at different time intervals.A retrospective
      study of computed tomography (CT) scan series of 698 normal orbits from 349
      skeletally normal subjects (202 men and 147 women) was enrolled. The age range of
      the patients was 0 to 21 years (mean, 10.2 years; SD, 5.8 years). A series of 12
      measurements were obtained from the CT scans of each subject. All CT images were
      obtained from patients who underwent CT of the facial bone, brain, and orbits at
      the Department of Radiology of 3 big hospital in Bangkok-Ramathibodi, Samitivej
      Srinakarin, and Bangkok hospital-since 2010 to 2015.The normal measurement values
      in the orbital region through the CT images, as the normal periorbital growth
      curve, will help improving diagnostic accuracy, staging of reconstruction,
      precision of corrective surgery, and follow-up of the Thai patients with
      craniofacial abnormalities such as front-ethmoidal meningoencephalocele,
      hypertelorism. These data may also apply to the related population in the
      southeast-Asian countries.

PMID- 30234717
TI  - Comparative Evaluation of the Prognostic Value Between the Ocular Trauma Score
      and the Pediatric Penetrating Ocular Trauma Score.
AB  - Controversy exists about the utility of the Ocular Trauma Score (OTS) in
      children. A new score was developed specifically for children-the Pediatric
      Penetrating Ocular Trauma Score (POTS)-which proved to be of prognostic value in
      young patients with penetrating eye injuries. The purpose of the study was to
      compare the prognostic value of OTS and POTS in children with open-globe injuries
      in a cohort of Brazilian children. This was a retrospective, interventional case
      series and included 37 children with open-globe injuries seen at the Santa Casa
      de Sao Paulo Emergency Service. Mean age was 8.0 +/- 3.9 years; 28 were male and
      9 female. All patients were reviewed on the basis of time and circumstance of
      injury, time of surgery, type of penetrating injury, initial and final visual
      acuity (VA), and concomitant eye disease. Both OTS and POTS categories were
      calculated based on specific variables. The final achieved VA was compared with
      the predicted VA for both scores with Kendall's test for significant association;
      the agreement between the predicted VA for both OTS and POTS was accessed with
      the Cohen kappa coefficient. The association between OTS and achieved VA was good
      (Kendall Tau-b = 0.511, P = 0.001), as well as between POTS and achieved VA
      (Kendall Tau-b = 0.422, P = 0.002). The agreement between the predicted VA for
      OTS and POTS was fair (kappa = 0.400). In conclusion, in this small cohort of
      Brazilian children with open-globe injuries, there was no superiority of one
      score over the other and both OTS and POTS underestimated the potential best
      corrected VA after treatment.

PMID- 30234719
TI  - Nazi Medicine-Part 1: Musculoskeletal Experimentation on Concentration Camp
      Prisoners During World War II.

PMID- 30234718
TI  - Traumatic Facial Fractures in Children and Adolescents.
AB  - This study showed a retrospective analysis of the incidence and pattern of
      traumatic facial fractures in a pediatric and adolescent population (<=18 years
      old) in China. The authors retrospectively reviewed 154 children and adolescent
      who had traumatic facial fractures and who were admitted to our university
      affiliated hospitals from 2005 to 2010. This study enrolled 109 males and 45
      females aged 11.9 +/- 5.2 years old. The incidence peaked around the periods of
      12 to 18 years in the male, <=6 and 16 to 18 years in the female. The most common
      etiologies were motor vehicle collisions (MVCs) (60, 39.0%), followed by high
      fall (40, 26.0%), low fall (32, 20.8%). The most common fracture sites were
      mandible (78, 50.6%) and nose (33, 21.4%), followed by orbit (31, 20.1%). A total
      of 35 (22.7%) patients suffered neurological deficit. The patients in the 12 to
      18 age range group accounted for the largest proportion of 54.5%. Fracture
      incidence showed peaks between the hours of 12:00 to 16:00 PM (33.7%), during the
      autumn season (30.5%) and on Friday to Sunday (50.0%). The most common etiology
      and fracture site were MVCs and mandible, respectively. Etiologies and patterns
      of traumatic facial fractures vary with age. Continued efforts toward injury
      prevention of traumatic facial fracture among the children and adolescents are
      warranted.

PMID- 30234720
TI  - CORR(r) International-Asia-Pacific: Aging in the Asia-Pacific-The Elephant in the
      Room.

PMID- 30234721
TI  - Innate immunity and Toll-like receptor signaling in the pathogenesis of
      scleroderma: advances and opportunities for therapy.
AB  - PURPOSE OF REVIEW: Systemic sclerosis (SSc) is an autoimmune connective tissue
      disease in which inflammation and cytokine dysregulation leads to skin fibrosis.
      Toll-like receptors (TLRs) are conserved pattern recognition receptors,
      recognizing pathogens danger-associated molecular patterns (DAMPs) that elicit a
      cascade of proinflammatory signaling. Recently, TLRs have been found to be
      critically important in SSc pathogenesis, with increased levels of the TLRs and
      their ligands present in the disease. Animal models have also been pivotal in
      delineating the role of these innate immune receptors in SSc. This current review
      examines the role of TLRs and the most recent evidence of the role of DAMPs and
      how these may be exploited therapeutically. RECENT FINDINGS: Increasingly,
      studies have demonstrated the key roles of TLR4 and other intracellular TLRs in
      mediating fibrosis in SSc patients and animal models. TLR4 activation appears a
      key point and novel DAMPs, expressed upon tissue damage, appear critical in
      mediating the profibrotic effect through a downstream enhancement of transforming
      growth factor beta. Deletion of Tenascin-C or a splice variant of fibronectin
      ameliorates animal models of skin fibrosis. Intracellular, nucleic acid sensing,
      TLR8 is critical in activating macrophages to secrete profibrotic molecules. The
      mechanism involves histone modification through epigenetic modifying enzymes.
      SUMMARY: TLRs are key therapeutic targets in SSc.

PMID- 30234722
TI  - New insights in myositis-specific autoantibodies.
AB  - PURPOSE OF REVIEW: The aim of this study was to provide the most recent evidence
      on clinical utility of myositis-specific autoantibodies (MSAs) in the management
      of patients with myositis. RECENT FINDINGS: In the last few years, several
      evidences have emerged on the clinical and pathogenetic role of established and
      novel MSA. Antisynthetase antibodies represent a reliable biomarker for pulmonary
      involvement also in patients with connective tissue diseases other than myositis.
      Antisignal recognition particle and antihydroxy-3-methylglutaryl coenzyme A
      reductase autoantibodies are able to induce complement-dependent muscle damage.
      Dermatomyositis-specific antibodies are useful indicators of clinical diversity.
      The pivotal role of antitranscription intermediary factor 1gamma autoimmune
      response in adult-age paraneoplastic dermatomyositis has been further asserted.
      AnticN1A and antifour-and-a-half LIM protein 1 antibodies are newly conceived
      myositis-related antibody specificities, which can contribute to patients'
      stratification into more homogeneous groups. SUMMARY: Distinct autoantibody
      associated clinical phenotypes can be predicted by extended MSA testing in serum.
      Standardization and validation of MSA laboratory detection methods is strongly
      recommended for better supporting myositis diagnosis, management and prognosis
      definition.

PMID- 30234723
TI  - T cells and cytokines in systemic sclerosis.
AB  - PURPOSE OF REVIEW: Dysregulation of both the innate and the adaptive immune
      systems has been identified in systemic sclerosis (SSc). However, the mechanisms
      underlying aberrant immune cell function remain poorly understood. T cells
      represent a predominant cell type in the affected tissues of patients,
      particularly in the early inflammatory stage of the disease. Antigen specificity
      of infiltrating T cells has not been identified; however, recent studies
      implicate specific T-cell subsets and the cytokines they produce in SSc
      pathogenesis by modulating the development of autoimmunity, inflammation and
      fibrosis. RECENT FINDINGS: The phenotype and function of distinct T-cell subsets
      have been identified in the affected tissues of SSc patients as well as in SSc
      animal models, implying their contribution to disease process. The molecular
      mechanisms underlying cytokine dysregulation by specific T-cell subpopulations
      are also becoming clear. SUMMARY: A better understanding of SSc pathogenesis will
      allow the development of novel therapeutic strategies targeting specific cell
      types and the pathways that are abnormally activated as well as the cytokines
      produced that may be directly involved with disease process. A further goal is to
      tailor therapy to address dysregulation specific to individual patients, leading
      to better efficacy and reduced toxicity.

PMID- 30234724
TI  - Recent progress in systemic sclerosis-interstitial lung disease.
AB  - PURPOSE OF REVIEW: Systemic sclerosis is a systemic autoimmune disorder wherein
      interstitial lung disease (ILD) is the major source or morbidity and mortality.
      Research into mechanisms of fibrosis and its intersection with autoimmunity,
      specifically lung fibrosis, has accelerated and been applied to autoimmune
      disorders such as scleroderma. This review highlights important emerging insights
      and treatment trials. RECENT FINDINGS: The important elements of this review
      focus on the challenges faced in identifying patients not only who develop lung
      disease but who are at a higher risk for progression given the heterogeneous
      natural history of ILD in scleroderma. Risk assessment scoring models using
      radiographic and physiologic parameters are highlighted and recent and ongoing
      clinical trials in scleroderma ILD are discussed. SUMMARY: The implications of
      much of this ongoing work is a potential paradigm shift in our ability to
      identify those patients at risk for progression, and to offer novel therapies
      that can limit the progression of inflammatory and fibrotic lung disease in this
      challenging group of patients.

PMID- 30234725
TI  - Gastrointestinal involvement in systemic sclerosis: diagnosis and management.
AB  - PURPOSE OF REVIEW: This review provides important updates in systemic sclerosis
      (SSc)-related gastrointestinal disease, with a particular focus on the diagnosis
      and management of dysmotility. RECENT FINDINGS: In the past 2 years, several
      studies were published that present interesting diagnostic insights into SSc and
      gastrointestinal dysmotility. Studies focusing on new therapies and the novel
      application of existing therapies, both in SSc and non-SSc-associated
      gastrointestinal dysmotility syndromes, demonstrate progress in the management of
      these challenging complications. SUMMARY: SSc gastrointestinal disease is
      heterogeneous in its clinical presentation, which presents a challenge in
      diagnosis and management. Objective studies may help to identify patterns of
      gastrointestinal dysmotility and more specifically target therapy. A variety of
      drugs are now available or are under study in the management of gastrointestinal
      dysmotility, such as prucalopride, intravenous immunoglobulin, pyridostigmine,
      linaclotide, relamorelin, and others. These drugs may improve symptoms and
      quality of life in SSc gastrointestinal patients. Combination therapies are also
      under study. Electroacupuncture, dietary intervention (e.g. medical nutrition
      therapy, low FODmap diet), and medical cannibus may also play a role in
      alleviating patient symptoms; however, more data are needed to define the role of
      these interventions in SSc.

PMID- 30234726
TI  - Optimizing the use of fibula in type II tibial hemimelia: early results.
AB  - We describe a technique for optimal use of fibula in reconstruction of type II
      tibial hemimelia. Six affected children with mean age of 1.4 years and treated
      over a 5-year period were reviewed. All underwent staged reconstruction by
      lowering the fibula to below knee level using Ilizarov soft tissue distraction,
      transfer of distal fibula under proximal tibia, and foot centralization. Mean
      follow-up period was 3.6 years (range: 1.6-6.05 years). Mean age at follow-up was
      4.4 years, and increase in length was 4.08 cm. Tibiofibular union and foot
      centralization were universally achieved. Mild residual equinovarus deformity was
      present in three children and braced. Our technique allowed significant length
      gain and foot centralization in toddlers without distraction osteogenesis.

PMID- 30234727
TI  - Normal value and range of the humerus-elbow-wrist angle in a sample of healthy
      children with even distributions of age, sex, and laterality.
AB  - This study was performed to evaluate the normal value of the humerus-elbow-wrist
      angle (HEWA) in a sample of healthy children with even distributions of age, sex,
      and laterality. A total of 168 radiographs of the elbows of healthy children with
      even distributions of age, sex, and laterality were reviewed. The mean HEWA was
      12.1 degrees  (range: 5 degrees -20 degrees ). The value of HEWA was
      significantly associated with increasing age. Neither sex nor side showed
      significant differences for the HEWA. The data should be useful for postoperative
      radiographic assessment of cubitus varus or valgus deformities.

PMID- 30234728
TI  - Marijuana Use in Pregnancy and While Breastfeeding.
AB  - The prevalence and perceived safety of marijuana use in pregnancy are increasing
      with expanding legalization. Marijuana crosses the placenta and passes into
      breast milk, resulting in fetal and neonatal exposure. Many women cite medical
      reasons for prenatal marijuana use such as nausea and vomiting of pregnancy,
      anxiety, and chronic pain. The scientific literature regarding marijuana in
      pregnancy is mixed, resulting in confusion among practitioners as to how to
      counsel women about risks of use. In addition, there is a paucity of literature
      related to marijuana use and breastfeeding. Existing pregnancy studies are
      predominantly retrospective cohorts with a reliance on self-report for
      ascertainment of exposure, which underestimates use. Many studies fail to adjust
      for important confounding factors such as tobacco use and sociodemographic
      differences. Despite the limitations of the existing evidence, there are animal
      and human data suggesting potential harm of cannabis use. The harms are
      biologically plausible given the role of the endocannabinoid system in pregnancy
      implantation, placentation, and fetal neurologic development. Two recent
      systematic reviews and meta-analyses found an association between marijuana use
      and adverse perinatal outcomes, especially with heavy marijuana use. In addition,
      three longitudinal cohort studies demonstrate a possible effect of prenatal
      marijuana exposure on long-term neurobehavioral outcomes. Marijuana use may be
      associated with growth restriction, stillbirth, spontaneous preterm birth, and
      neonatal intensive care unit admission. Therefore, women should be advised to
      refrain from using marijuana during pregnancy and lactation.

PMID- 30234729
TI  - Association of Implementing a Multidisciplinary Team Approach in the Management
      of Morbidly Adherent Placenta With Maternal Morbidity and Mortality.
AB  - OBJECTIVE: To compare maternal outcomes in patients with morbidly adherent
      placenta managed in a multidisciplinary team setting compared with standard care.
      DATA SOURCES: A literature search was performed for publications reporting
      multidisciplinary pathways in the management of cesarean delivery for patients
      with morbidly adherent placenta. EMBASE, MEDLINE, PubMed, PubMed Central,
      ClinicalTrials.gov, and Cochrane databases were searched. METHODS OF STUDY
      SELECTION: Databases were searched for studies reporting maternal morbidity of
      patients with morbidly adherent placenta managed by a multidisciplinary team in a
      specialist center compared with standard care. Two independent reviewers applied
      inclusion and exclusion criteria to select included articles, with differences
      agreed by consensus. A total of 252 citations were reviewed; six studies
      comprising 461 patients were selected for the analysis. TABULATION, INTEGRATION,
      AND RESULTS: Literature search was performed using Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results were reported
      as mean differences or pooled odds ratios (ORs) with 95% CIs. Estimated blood
      loss was significantly reduced in the multidisciplinary team group (mean
      difference -1.1 L, 95% CI -1.9 to -0.4, P=.004) and these patients had lower
      transfusion requirements (mean difference -2.7 units, 95% CI -4.1 to -1.2,
      P=.040). Those treated in a standard care setting were more likely to develop
      complications (OR 2.5, 95% CI 1.5-4.0, P<.001); however, there was no difference
      in length of stay between the two groups. CONCLUSION: This meta-analysis
      highlights the improved maternal outcomes in patients with morbidly adherent
      placenta when managed by a multidisciplinary team in a specialist center. High
      risk complex cases warrant expert management in centralized units.

PMID- 30234730
TI  - Low pretreatment serum concentration of vitamin D at breast cancer diagnosis in
      postmenopausal women.
AB  - OBJECTIVE: The aim of the study was to evaluate the rate of and risk factors for
      low pretreatment vitamin D (VitD) levels in postmenopausal breast cancer (BC)
      women, compared with postmenopausal women without BC. METHODS: A cross-sectional
      clinical study was conducted to compare 209 women with BC (case group) to 418
      women without BC (control group), age range: 45 to 75 years. The case group
      consisted of women diagnosed with BC, amenorrhea >=12 months, aged >=45 years,
      without use of medication or clinical conditions that might interfere with VitD
      levels. The control group consisted of women with amenorrhea >=12 months, aged
      >=45 years, without BC. The groups were matched for age and time since menopause,
      at a case: control ratio of 1:2. Serum 25-hydroxyvitamin-D [25(OH)D]
      concentration was measured in all women 10 to 20 days after BC diagnosis and
      before the proposed treatment. Serum levels >=30 ng/mL were defined as
      sufficient. The Student's t test or gamma distribution, chi test, and logistic
      regression (odds ratio, OR) were used for statistical analysis. RESULTS: The BC
      group had a higher body mass index (BMI) and higher percentage of obesity than
      the control group (57.4% vs 40.2%, P < 0.0001). In addition, rates of
      insufficient (20-29 ng/mL) and deficient (<20 ng/mL) 25(OH)D levels were higher
      in BC patients than in controls (55.6% vs 49.3%, P = 0.039 and 26.2% vs 20.3%, P
      = 0.018), respectively. In risk analysis (adjusted for age, time since menopause,
      and BMI), BC patients had a 1.5-fold higher risk of developing low VitD levels
      (OR = 1.52, 95% CI, 1.04-2.22, P = 0.029) than women without BC. CONCLUSIONS:
      Postmenopausal women had an increased risk of VitD deficiency at the time of BC
      diagnosis, associated with a higher rate of obesity, than women of the same age
      group without cancer.

PMID- 30234731
TI  - Appropriate evaluation of postmenopausal bleeding.
AB  - : In clinical practice, although only 3% to 7% of women with postmenopausal
      bleeding (PMB) will ultimately be found to have cancer, it is the clinician's
      responsibility to ensure that endometrial cancer is not present. The diagnostic
      evaluation of PMB has evolved greatly. This Practice Pearl addresses the
      appropriate evaluation of women with PMB.

PMID- 30234732
TI  - Reliability and validity of the shortened Singapore versions of the Chedoke Arm
      and Hand Activity Inventory.
AB  - Upper limb deficits are common sequelae after a stroke and negatively affect
      daily living and quality of life. The use of outcome measures to evaluate upper
      limb function is essential to assess sensorimotor recovery and to determine the
      effectiveness of rehabilitation. The aim of this study was to estimate the
      construct validity and inter-rater reliability of three shortened versions of the
      Singapore version of the Chedoke Arm and Hand Activity Inventory (CAHAI-SG)
      comprising seven, eight, and nine test items. The sample consisted of 55
      inpatients with acute/subacute stroke to whom the CAHAI-SG, Fugl-Meyer Assessment
      of Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT) were
      administered. To estimate convergent and discriminative construct validity,
      Spearman's rank correlation coefficient and 95% confidence intervals were
      computed for CAHAI-SG scores with FMA-UE and ARAT scores. Reliability was
      estimated using intraclass correlation coefficient (relative reliability) and the
      standard error of measurement (absolute reliability). Convergent validity with
      the FMA-UE was 0.79, 0.80, and 0.81 for seven-item, eight-item, and nine-item
      versions of the CAHAI-SG, respectively, and 0.81 with the ARAT for all shortened
      versions. Discriminative validity with the FMA-UE pain subscale was between 0.37
      and 0.38. The absolute reliability was 3.09, 3.65, and 3.98, and relative
      reliability was 0.96, 0.95, and 0.96 for the seven-item, eight-item, and nine
      item versions, respectively. All shortened versions of the CAHAI-SG demonstrated
      similar psychometric properties to the full (13 item) version, meaning clinicians
      may use these shorter versions that require less time to administer and score.

PMID- 30234733
TI  - Effects of functional electrical stimulation-cycling on shoulder pain and
      subluxation in patients with acute-subacute stroke: a pilot study.
AB  - Functional electrical stimulation (FES)-cycling is a technique used to provide
      voluntary muscle contraction during a functional task. The aims were primarily to
      determine the effects of FES-cycling on shoulder pain and subluxation, and
      secondarily to evaluate the improvement of upper extremity motor function in
      patients with acute-subacute stroke patient. In this prospective trial, 21
      patients with acute-subacute stroke, randomly assigned into the FES-cycling group
      or the standard rehabilitation program (control group). Analyses of shoulder
      subluxation were carried out by radiography. The numeric rating scale was used to
      evaluate the intensity of pain, Fugl-Meyer and Frenchay arm tests for motor
      function, and functional independence measure for functional status. The outcome
      data were evaluated at baseline and at the end of 4-week treatment. Intragroup
      comparisons showed improvement of acromiohumeral distance, Fugl-Meyer assessment,
      and functional independence measure in both groups after treatment. In intergroup
      comparison, FES-cycling group exerted better outcomes in shoulder pain compared
      with the control group (P=0.015). Correlation analyses demonstrated only positive
      correlation between shoulder subluxation and pain (P=0.022). FES-cycling was
      superior to standard rehabilitation therapy for shoulder pain relief in patients
      with acute-subacute stroke. Therefore, combining FES-cycling with a standard
      rehabilitation program alleviates shoulder pain and may prevent development of
      shoulder subluxation over time.

PMID- 30234734
TI  - Manual function of the unaffected upper extremity can affect functional outcome
      after stroke.
AB  - Traditionally, motor deficits of ipsilesional side, generally considered as the
      unaffected side, have been investigated less and the influence of the impairment
      is unknown. To evaluate the association between the manual function test (MFT) of
      nonparetic limb and poststroke functional outcome. We conducted a retrospective
      analysis of 71 hemiplegic patients with stroke. MFT on both sides was routinely
      measured at admission and 1 month later after admission by an experienced
      occupational therapist. The parameters of functional outcome after stroke were
      measured with the total score of functional independence measure (FIM) and the
      self-care subscore of FIM. Age, initial cognitive function, and MFT of the
      affected hand and unaffected hand were each significant factors for independently
      predicting short-term functional outcome after stroke. Linear regression analysis
      showed that initial MFT score of unaffected side is a significant predictor for 1
      month follow-up subscore FIM (P<0.0001) and total FIM score (P<0.0001). Our
      findings suggests that initial MFT score of the nonparetic side has a significant
      correlation with functional outcome. Therefore, it is important to conduct MFT on
      the nonparetic side as well as the paretic side. Furthermore, it is necessary to
      undergo rehabilitation therapy on the nonparetic side.

PMID- 30234735
TI  - Bioengineering the innate vasculature of complex organs: what have we learned so
      far.
AB  - PURPOSE OF REVIEW: Engineering vasculature that meets an organ's specific
      physiology and function is a fundamental step in organ bioengineering. In this
      article, we review approaches for engineering functional vasculature for organ
      bioengineering, with an emphasis on the engineering of organ-specific endothelium
      and vasculature. RECENT FINDINGS: Recent advances in hydrogel-based engineering
      of vascularized organ bud enable vascular regeneration in self-assembled cellular
      niche containing parenchymal and stromal cells. The emerging technology of whole
      organ decellularization provides scaffold materials that serve as extracellular
      niche guiding vascular regeneration to recapitulate native organ's vascular
      anatomy. Increasing morphological and molecular evidences suggest endothelial
      heterogeneity across different organs and across different vascular compartments
      within an organ. Deriving organ-specific endothelium from pluripotent stem cells
      has been shown to be possible by combining endothelial induction with parenchymal
      differentiation. SUMMARY: Engineering organ-specific vasculature requires the
      combination of organ-specific endothelium with its unique cellular and
      extracellular niches. Future investigations are required to further delineate the
      mechanisms for induction and maintenance of organ-specific vascular phenotypes,
      and how to incorporate these mechanisms to engineering organ-specific
      vasculature.

PMID- 30234736
TI  - Three-dimensional bioprinting for organ bioengineering: promise and pitfalls.
AB  - PURPOSE OF REVIEW: Loss of organ function is a critical issue that threatens a
      patient's life. Currently, the only available treatment is organ transplantation;
      however, shortage of donor organs, histocompatibility, and life-long
      immunosuppression present major challenges. Three-dimensional bioprinting
      technology holds a promising solution for treating organ failure by fabricating
      autologous tissues and organs for transplantation. To biofabricate a functional
      tissue, target-cell types are combined with an appropriate biomaterial for
      structural support and a bioink that supports cell function and maturation.
      Bioprinted structures can mimic the native tissue shape and functionality. RECENT
      FINDINGS: The main goal of three-dimensional bioprinting is to produce functional
      tissues/organs; however, whole organ printing has not been achieved. There have
      been recent advances in the successful three-dimensional bioprinting of numerous
      tissues. This review will discuss the types of bioprinters, biomaterials,
      bioinks, and the fabrication of various constructs for repair of vascular,
      cartilage, skin, cardiac, and liver tissues. These bioprinted tissue constructs
      have the potential to be used to treat tissues and organs that have been damaged
      by injury or disease. SUMMARY: Three-dimensional bioprinting technology offers
      the ability to fabricate three-dimensional tissue structures with high precision,
      fidelity, and stability at human clinical scale. The creation of complex tissue
      architectures with heterogeneous compositions has the potential to revolutionize
      transplantation of tissues and organs.

PMID- 30234737
TI  - Progress and challenges in lung xenotransplantation: an update.
AB  - PURPOSE OF REVIEW: Recent progress in genetic engineering has facilitated
      development of transgenic donor animals designed to overcome the known barriers
      to discordant xenotransplantation, and greatly accelerated progress in the field
      of xenotransplantation. Here we review and summarize recent progress in lung
      xenotransplantation, and discuss possible additional genetic modifications and
      other interventions that may further advance the use of pulmonary xenografts
      towards clinical applications based on known mechanisms of xeno lung injury.
      RECENT FINDINGS: Ex-vivo lung perfusion experiments have shown that the addition
      of human complement (hCD46, hCD55), coagulation (hEPCR, hVWF, hTBM, hTFPI,
      hCD39), or anti-inflammatory pathway regulatory genes (HO-1, HLA-E), and the
      knockout (KO) of major porcine carbohydrates (GalT, Neu5Gc, B4Gal) have each
      protective effects on lung survival and function. The use of these transgenes in
      multitransgenic donor organs, targeting several known xenogeneic rejection
      mechanisms, combined with drug treatments addressing remaining known rejection
      pathways, have led to prolonged recipient survival of up to 31 days with in some
      cases preserved live-supporting organ function of the transplanted graft for
      several days. Pulmonary vascular resistance elevation, which has been found to be
      associated with high thromboxane levels and has been the major failure reason of
      xenogeneic lung grafts in the past years, has been successfully attenuated by the
      addition of a thromboxane synthase inhibitor (1-Benzylimidazole). Currently, the
      predominant failure mechanism of xenogeneic lung grafts is an inflammatory
      process, leading to vascular barrier function injury with interstitial and
      trachea edema. Work with other pig organs in primate models show that regimens
      based on costimulatory pathway blocking antibodies prolong xenograft function for
      months to years, suggesting that once initial lung inflammation mechanisms are
      fully controlled, clinically useful application of pig lung xenografts may be
      feasible. SUMMARY: The use of multitransgenic donor pigs coupled with drugs
      targeting complement activation, coagulation, and inflammation have significantly
      improved the survival of xenogeneic pig lungs both during ex vivo human blood
      perfusion and in life-supporting in vivo models, and for the first time allowed
      consistent life-supporting function of lung xenografts. Overcoming delayed loss
      of vascular barrier function injury appears to be within reach, and will be
      essential to make lung xenografts a clinically relevant treatment option.

PMID- 30234738
TI  - Implementation and Evaluation of Training for Ultrasound-Guided Vascular Access
      to Small Vessels Using a Low-Cost Cadaver Model.
AB  - OBJECTIVES: Critically ill neonatal and pediatric patients often require central
      vascular access. Real-time ultrasound guidance for central venous catheterization
      is beneficial. Because the diameter of central veins is much smaller in neonates
      than in adults, extensive training is needed to master the visualization and
      catheterization of central veins in neonates. This study assessed the learning
      effect of a standardized simulation-based teaching program on ultrasound-guided
      cannulation in a low-cost cadaver tissue model. DESIGN: This simulation-based
      prospective study assessed physician competence in the ultrasound-guided central
      venous catheterization procedure. Analyses were conducted before and after the
      teaching course. SETTING: Pediatric simulation center at a tertiary care center.
      SUBJECTS: Staff physicians from the Neonatal ICU and PICUs at the Medical
      University of Vienna. INTERVENTIONS: Two latex tubes, with internal diameters of
      2 and 4 mm, were inserted in parallel into cadaver tissue to mimic vessels and
      create a model for central venous catheterization. MEASUREMENTS AND MAIN RESULTS:
      Under ultrasound guidance, each participant attempted to puncture and insert a
      guide-wire into each of the latex tubes using in-plane and out-of-plane
      techniques, both before and after the teaching course. The training program was
      assessed using a questionnaire and a performance checklist. Thirty-nine
      physicians participated in this study. The rates of failure of guide-wire
      insertion into 2-mm tubes were significantly lower after than before the teaching
      course, using both in-plane (p = 0.001) and out-of-plane (p = 0.004) techniques.
      Teaching, however, did not significantly reduce the insertion failure rate into 4
      mm tubes, either in-plane (p = 0.148) or out-of-plane (p = 0.069). The numbers of
      successful cannulations on the first attempt increased after the teaching in all
      methods (p = 0.001). CONCLUSIONS: Implementation of a skills training program for
      ultrasound-guided central venous catheterization in a cadaver tissue model was
      feasible and cost- and time-effective. The number of attempts until successful
      cannulation of small vessels (2-mm tube) was significantly lower after than
      before the standardized teaching program.

PMID- 30234739
TI  - Pediatric Ventilator-Associated Events: Analysis of the Pediatric Ventilator
      Associated Infection Data.
AB  - OBJECTIVES: To compare the prevalence of infection applying the proposed
      pediatric ventilator-associated events criteria versus clinician-diagnosed
      ventilator-associated infection to subjects in the pediatric ventilator
      associated infection study. DESIGN: Analysis of prospectively collected data from
      the pediatric ventilator-associated infection study. SETTING: PICUs of 47
      hospitals in the United States, Canada, and Australia. PATIENTS: Two-hundred
      twenty-nine children ventilated for greater than 48 hours who had respiratory
      secretion cultures performed to evaluate for suspected ventilator-associated
      infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Applying the
      proposed pediatric ventilator-associated event criteria, 15 of 229 subjects in
      the ventilator-associated infection study qualified as "ventilator-associated
      condition" and five of 229 (2%) met criteria for "infection-related ventilator
      associated complication." This was compared with 89 of 229 (39%) diagnosed as
      clinical ventilator-associated infection (Kappa = 0.068). Ten of 15 subjects
      identified as ventilator-associated condition did not meet criteria for infection
      related ventilator-associated complication primarily because they did not receive
      4 days of antibiotics. Ventilator-associated condition subjects were similar
      demographically to nonventilator-associated condition subjects and had similar
      mortality (13% vs 10%), PICU-free days (6.9 +/- 7.7; interquartile range, 0-14 vs
      9.8 +/- 9.6; interquartile range, 0-19; p = 0.25), but fewer ventilator-free days
      (6.6 +/- 9.3; interquartile range, 1-15 vs 12.4 +/- 10.7; interquartile range, 0
      22; p = 0.04). The clinical ventilator-associated infection diagnosis in the
      ventilator-associated infection study was associated with fewer PICU-free days
      but no difference in mortality or ventilator-free days. CONCLUSIONS: The
      ventilator-associated event criteria appear to be insensitive to the clinical
      diagnosis of ventilator-associated infection. Differentiation between ventilator
      associated condition and infection-related ventilator-associated complication was
      primarily determined by the clinician decision to treat with antibiotics rather
      than clinical signs and symptoms. The utility of the proposed pediatric
      ventilator-associated event criteria as a surrogate for ventilator-associated
      infection criteria is unclear.

PMID- 30234740
TI  - Prevalence and Prognostic Value of Abnormal Liver Test Results in Critically Ill
      Children and the Impact of Delaying Parenteral Nutrition.
AB  - OBJECTIVES: In the Early versus Late Parenteral Nutrition in the Pediatric ICU
      randomized controlled trial, delaying parenteral nutrition to beyond day 7 (late
      parenteral nutrition) was clinically superior to supplemental parenteral
      nutrition initiated within 24 hours (early parenteral nutrition), but resulted in
      a higher rise in bilirubin. We aimed to document prevalence and prognostic value
      of abnormal liver tests in the PICU and the impact hereon of withholding early
      parenteral nutrition. DESIGN: Preplanned secondary analysis of the Early versus
      Late Parenteral Nutrition in the Pediatric ICU randomized controlled trial. Total
      bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl
      transpeptidase, alkaline phosphatase plasma concentrations were measured
      systematically in PICU. Liver test analyses were adjusted for baseline
      characteristics including severity of illness. SETTING: Three PICUs in Belgium,
      the Netherlands, and Canada. PATIENTS: As neonatal jaundice was considered a
      confounder, only the 1,231 of the 1,440 Early versus Late Parenteral Nutrition in
      the Pediatric ICU-patients 28 days to 17 years old were included. INTERVENTIONS:
      Late parenteral nutrition as compared with early parenteral nutrition.
      MEASUREMENTS AND MAIN RESULTS: During the first seven PICU days, the prevalence
      of cholestasis (> 2 mg/dL [34.2 MUmol/L] bilirubin) ranged between 3.8% and 4.9%
      and of hypoxic hepatitis (>= 20-fold upper limit of normality for alanine
      aminotransferase and aspartate aminotransferase) between 0.8% and 2.2%, both
      unaffected by the use of parenteral nutrition. Throughout the first week in PICU
      plasma bilirubin concentrations were higher in late parenteral nutrition patients
      (p < 0.05), but became comparable to early parenteral nutrition patients as soon
      as parenteral nutrition was started on day 8. Plasma concentrations of gamma
      glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase, and
      aspartate aminotransferase were unaffected by parenteral nutrition. High day 1
      plasma concentrations of gamma-glutamyl transpeptidase, alanine aminotransferase,
      and aspartate aminotransferase (p <= 0.01), but not alkaline phosphatase, were
      independent risk factors for PICU mortality. Day 1 plasma bilirubin
      concentrations displayed a U-shaped association with PICU mortality, with higher
      mortality associated with bilirubin less than 0.20 mg/dL and greater than 0.76
      mg/dL (< 3.42 MUmol/L and > 13 MUmol/L) (p <= 0.01). CONCLUSIONS: Overt
      cholestasis and hypoxic hepatitis were rare and unrelated to the nutritional
      strategy. However, withholding parenteral nutrition up to 1 week in PICU
      increased plasma bilirubin. A mild elevation of bilirubin on the first PICU day
      was associated with lower risk of death and may reflect a stress response, rather
      than true cholestasis.

PMID- 30234741
TI  - Correlation of Bedside Pediatric Early Warning System Score to Interventions
      During Peritransport Period.
AB  - BACKGROUND: The Bedside Pediatric Early Warning System score is a validated
      measure of severity of illness in acute care inpatient settings. Its potential as
      a remote assessment tool for interfacility transport has not been evaluated. We
      hypothesized that the Bedside Pediatric Early Warning System score was associated
      with need for intervention during the peritransport period and patient
      disposition. METHODS: We retrospectively evaluated children transported by a
      regional pediatric team during a 6-month period. Bedside Pediatric Early Warning
      System scores were calculated at the triage phone call, the transport team
      arrival, and at transfer of care to the hospital team. The primary outcome was
      the receipt of significant intervention during the peritransport period, with
      additional outcomes of destination (ICU, ward, emergency department) in the
      regional hospital. Scores are presented as median values (interquartile range).
      RESULTS: There were 564 children who underwent transport; 139 (25%) received
      interventions; and 205 (36%) were transferred to the PICU, 231 (41%) to the ward,
      and 127 (23%) to the emergency department. Scores were 2 (1-5; median
      interquartile range) in children receiving no in-transport interventions, 8 (5
      11) in children receiving any intervention (p < 0.001), and 10 (7-14) in children
      receiving more than one intervention. Children transferred to the PICU had higher
      scores 6 (3-10), than children transferred to a ward 3 (1-6) or the emergency
      department 2 (1-3) (p < 0.001). CONCLUSIONS: The Bedside Pediatric Early Warning
      System score at the time of initial referral is a useful measure of severity of
      illness reflected by the subsequent provision of significant peritransport
      intervention and the transfer destination.

PMID- 30234742
TI  - External Validation of the "Quick" Pediatric Logistic Organ Dysfunction-2 Score
      Using a Large North American Cohort of Critically Ill Children With Suspected
      Infection.
AB  - OBJECTIVES: A quick Pediatric Logistic Organ Dysfunction 2 score on day 1,
      consisting of tachycardia, hypotension, and altered mentation, was shown to
      predict mortality with an area under the receiver operating characteristic curve
      of 82% (95% CI, 76-87%) in children admitted to a PICU with suspected infection.
      We performed an external validation of the quick Pediatric Logistic Organ
      Dysfunction 2, including its performance in predicting mortality in specific age
      groups. DESIGN: Analysis of retrospective data obtained from the Virtual
      Pediatric Systems PICU registry. SETTING: Prospectively collected clinical
      records from 130 participating PICUs in North America. PATIENTS: Children
      admitted between January 2009 and December 2014, with a diagnosis of infection at
      discharge, for whom all required data were available. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Systolic blood pressures, heart rates, and Glasgow
      Coma Scale scores were used to evaluate the quick Pediatric Logistic Organ
      Dysfunction 2 using area under the receiver operating characteristic curve
      analysis. Performance was compared with Pediatric Risk of Mortality 3 and
      Pediatric Index of Mortality 2 risk scores. Data from 42,196 children with
      complete data were analyzed, with median age 2.7 years (interquartile range, 0.7
      8.8 yr; range 0-18 yr) and a 4.27% mortality rate. Mortality was 13.4% for quick
      Pediatric Logistic Organ Dysfunction 2 greater than or equal to 2 and 2.5% for
      quick Pediatric Logistic Organ Dysfunction 2 less than 2, representing a false
      negative rate of 49.5%. Also 311 children (17%) who died had a quick Pediatric
      Logistic Organ Dysfunction 2 score of 0. The area under the receiver operating
      characteristic curve was 72.6% (95% CI, 71.4-73.8%) for quick Pediatric Logistic
      Organ Dysfunction 2, compared with 85.0% (95% CI, 84.0-86.0%) for Pediatric Risk
      of Mortality 3 and 81.5% (95% CI, 80.5-82.5%) for Pediatric Index of Mortality 2.
      Performance of quick Pediatric Logistic Organ Dysfunction 2 was worst in the
      greater than 12 years age group (area under the receiver operating characteristic
      curve, 67.8%; 95% CI, 65-70.5) and best in the less than 1 month age group (area
      under the receiver operating characteristic curve, 78.9%; 95% CI, 75.3-82.4).
      CONCLUSIONS: Quick Pediatric Logistic Organ Dysfunction 2 performed markedly
      worse in our cohort, compared with the original study, and the high rate of false
      negatives limits its clinical utility in our population. Further work is needed
      to develop a robust quick pediatric sepsis diagnostic tool for both research and
      clinical care.

PMID- 30234743
TI  - Diurnal Variation of Choroidal Thickness in Primary Open-angle Glaucoma.
AB  - PURPOSE: To investigate, in primary open-angle glaucoma (POAG) and healthy
      subjects, the pattern and magnitude of diurnal variation in macular choroidal
      thickness (mCT). METHODS: A prospective study was conducted on Koreans comprising
      21 patients with POAG and 17 healthy subjects. All underwent mCT, systemic blood
      pressure (BP), and intraocular pressure measurements during the daytime at 5 time
      points (8 AM, 11 AM, 2 PM, 5 PM, and 8 PM). The mCT was determined at 5 sites
      using swept-source optical coherence tomography. RESULTS: In the healthy
      subjects, the mean mCT was 233.63+/-50.98 MUm at 8 AM, which then decreased
      gradually to 2 PM (206.02+/-45.91, P=0.015) and increased again in the evening (8
      PM; 228.12+/-51.69, P=0.030). The mean mCT in the POAG patients at 8 AM, 246.50+/
      48.94 MUm, also decreased to 226.77+/-51.48 at 2 PM (P=0.027) but did not
      increase in the evening (229.07+/-50.87; P=0.566). However, the overall diurnal
      variation of mean mCT was not statistically significant in either group (P=0.179
      and 0.164, respectively). The systolic BP, diastolic BP, and mean ocular
      perfusion pressure of the POAG had the peak value at 8 AM and the trough value at
      8 PM (P=0.001, 0.002, and <0.001). CONCLUSIONS: The mCT in the POAG patients did
      not increase in the evening relative to the healthy subjects' pattern. However,
      the diurnal mCT values measured in the healthy subjects and POAG patients were
      not statistically significant.

PMID- 30234744
TI  - Clinical Results and Utility of Herpesviruses Multiplex Polymerase Chain
      Reaction: Assessment of Aqueous Humor Samples From Patients With Corneal
      Endotheliitis and High Intraocular Pressure.
AB  - PURPOSE: The main purpose of this study was to evaluate herpesvirus infection in
      patients with corneal endotheliitis and high intraocular pressure (IOP) using
      multiplex polymerase chain reaction (PCR) in aqueous humor samples. MATERIALS AND
      METHODS: This was a retrospective, observational study of immunocompetent
      patients living in South Korea. Eligible subjects had typical corneal
      endotheliitis with an IOP>=21 mm Hg or required antiglaucoma medication.
      Multiplex PCR was performed using aqueous humor samples obtained at first visit
      to detect the DNA of 6 herpesviruses. RESULTS: Forty-two eyes from 42 patients
      with >6 months' follow-up were analyzed. Of these, 16 were herpesvirus-positive:
      3 herpes simplex virus 1, 3 varicella-zoster virus, 9 cytomegalovirus, and 1
      Epstein-Barr virus. Eyes with coin-shaped or fine keratic precipitates (kps),
      high IOP, and a low baseline endothelial cell count were more likely to show a
      positive result on multiplex PCR. Univariate analysis showed that male sex
      (P=0.014), a previous history of uveitic glaucoma (P=0.048), and the presence of
      fine kps (P=0.031) were significantly associated with a positive PCR result. On
      multivariate analysis, male sex (P=0.010) and a previous history of uveitic
      glaucoma (P=0.031) showed a significant positive association. CONCLUSIONS:
      Cytomegalovirus was the most commonly detected herpesvirus in patients with
      corneal endotheliitis and high IOP. A positive PCR result was seen more
      frequently in male individuals and patients with fine kps or a history of uveitic
      glaucoma.

PMID- 30234745
TI  - Choroidal Detachment and Increased Intraocular Pressure in a Case of Secondary
      Pulmonary Hypertension.
AB  - PURPOSE: To report a case of secondary pulmonary hypertension, choroidal
      detachment, and increased intraocular pressure in a patient with a congenital
      ventricular septal defect. METHODS: Case report. PATIENT: A 36-year-old man with
      congenital ventricular septal defect developed dilated and congested conjunctival
      and episcleral veins, high intraocular pressure, and choroidal detachment.
      RESULTS: The right eye had secondary glaucoma, myopia, and choroidal detachment.
      He had severe pulmonary hypertension and decreased heart function. After
      successful treatment for heart failure, intraocular pressure was reduced, the
      refractive state returned to normal, choroidal detachment was reversed, and
      visual acuity improved. CONCLUSION: Secondary pulmonary hypertension resulting
      from a congenital ventricular septal defect caused serious optic abnormalities
      that resolved substantially with appropriate treatment of the pulmonary
      hypertension.

PMID- 30234746
TI  - Acute Secondary Optic Neuropathy as a Complication of a Single Episode of Acutely
      Raised Intra Ocular Pressure - a Case Series.
AB  - PURPOSE: The purpose of this case series is to report development of Acute
      Secondary Optic Neuropathy due to optic nerve injury associated with single
      episode of acutely raised intraocular pressure of varying aetiologies. METHODS:
      Retrospective review of a series of three consecutive cases diagnosed at
      University hospitals of Coventry and Warwickshire and review of published
      literature. RESULTS: Three cases respectively with Posner Schlossman syndrome
      (PSS), acute idiopathic hypertensive anterior uveitis, and primary acute angle
      closure (PAC) initially presented with raised intraocular pressures (IOPs) of 38
      68?mm Hg. All cases were treated initially with medical management and the PAC
      case had subsequent Nd:YAG laser peripheral iridotomy. All three cases developed
      acute optic nerve injury with reduced vision, an afferent pupillary defect and
      optic disc swelling which subsequently persisted as optic neuropathy with
      sectoral optic atrophy and disc pallor. CONCLUSION: This rare cases series
      highlights the importance of increased awareness of the possibility of developing
      acute secondary optic neuropathy in patients with acutely raised IOP. Based on
      the acute clinical features, including disc edema with disc hemorrhages and an
      afferent pupillary defect the most likely pathophysiology of the resultant optic
      nerve injury is the acute impact of high IOP on optic nerve head perfusion. This
      appears similar to Non Arteritic Anterior Ischaemic Optic Neuropathy (NAAION).
      Other systemic and local risk factors may also contribute. Appropriate timely
      management to reduce the acutely raised IOP are essential but may not be
      sufficient in preventing optic neuropathy due to changes at presentation.

PMID- 30234747
TI  - A Case of Pseudomonas Orbital Cellulitis Following Glaucoma Device Implantation.
AB  - PURPOSE: Orbital cellulitis is a rare complication of aqueous tube shunt surgery.
      Nine cases have been described in the literature, though the microbiologic
      etiology is rarely reported. Management with intravenous antibiotics and/or
      explantation has been described. METHODS: Case Report and Literature Review.
      CASE: A 64-year-old woman developed pain, periorbital swelling, limited
      extraocular motility, proptosis, and conjunctival injection three days following
      implantation of an Ahmed Glaucoma Valve. CT of the orbits with contrast
      demonstrated soft tissue fat stranding consistent with orbital inflammation.
      Initial medical management with topical and intravenous ceftriaxone and
      vancomycin was unsuccessful. Surgical removal of the implant was performed and
      intra-operative cultures demonstrated florid Pseudomonas Aeruginosa growth.
      Antibiotic coverage was changed to Piperacillin-Tazobactam for three days, with
      eventual resolution of her orbital symptoms. CONCLUSIONS: We report the first
      case of orbital cellulitis after implantation of a glaucoma device associated
      with Pseudomonas aeruginosa. Failure of intravenous and topical antibiotics led
      to explantation of the valve and targeted intravenous antibiotic therapy with
      subsequent clinical improvement.

PMID- 30234748
TI  - Short-term Efficacy and Safety of a Latanoprost/Carteolol Fixed Combination
      Switched From Concomitant Therapy to in Patients With Primary Open-angle Glaucoma
      or Ocular Hypertension.
AB  - PURPOSE: We prospectively investigated the efficacy and safety of switching from
      concomitant latanoprost and carteolol hydrochloride (CH) to a
      latanoprost/carteolol fixed combination (LCFC) in patients with primary open
      angle glaucoma or ocular hypertension. PATIENTS AND METHODS: A total of 43
      patients (43 eyes) who were using latanoprost (once daily in the evening) and CH
      (once daily in the morning) concomitantly were switched to LCFC (once daily in
      the morning) with no washout interval. The primary efficacy endpoint was change
      in intraocular pressure (IOP) between baseline (before switching) and 1 and 3
      months after switching. Systemic blood pressure and pulse rate, corneal
      epithelial defects, and tear film break-up time (TBUT) were also compared before
      and 1 and 3 months after switching. A questionnaire was administered 1 month
      after switching to investigate ocular comfort and treatment preferences. Adverse
      reactions and dropouts were recorded. RESULTS: There was no significant
      difference in IOP after switching to LCFC (15.0+/-2.6, 15.1+/-2.4, and 15.0+/-2.4
      mm Hg at baseline and at 1 and 3 months, respectively). There was a significant
      decrease in corneal epithelial defects and significant increase in TBUT, without
      significant changes in systemic blood pressure or pulse rate. Three patients
      (7.3%) preferred concomitant latanoprost and CH; 33 (80.5%) preferred the LCFC.
      One patient each (9.3%) discontinued treatment because of foreign body sensation,
      blepharitis, increased IOP, or loss to follow-up. CONCLUSIONS: Switching from
      concomitant latanoprost and CH to LCFC led to similar IOP control with good
      safety and patient acceptance, at least in the short term.

PMID- 30234749
TI  - XEN Gel Stent to Treat Intraocular Hypertension after Dexamethasone-implant
      Intravitreal Injections: 5 Cases.
AB  - INTRODUCTION: Intravitreal injections (IVI) of slow-release dexamethasone (DEX)
      are generally well tolerated. Ocular hypertension (OHT) and cataracts are the
      most common adverse effects of DEX-implant (DEX-I). MATERIAL AND METHODS: The
      cases reported concern five eyes in four DEX-I IVI high-responder patients whose
      intraocular pressure (IOP) returned to normal after administration of a XEN gel
      stent with mitomycin subconjunctival injection, thus allowing the continued use
      of DEX-I which was the only therapeutic option for these patients. All patients
      were pure steroid responders with normal optic nerves. RESULTS: No hypertension
      was observed in any of the eyes after DEX-implant intravitreal reinjection
      following XEN-surgery.All patients were successfully treated with XEN surgery and
      were retreated with DEX-implant with no further increase in IOP. The mean
      duration of follow-up after the MIGS procedure was five months (min-max; 2-12).
      None of the patients required needling. CONCLUSION: XEN gel stent would appear to
      represent a safe and effective solution for treating steroid-induced
      hypertension. It allows for the medium and long-term use of DEX-I in high
      responders. It could be of clinical interest to study this combination in a
      prospective trial with a large number of patients and long-term follow-up.

PMID- 30234750
TI  - Compliance With Primary Open-angle Glaucoma and Primary Open-angle Glaucoma
      Suspect Preferred Practice Patterns in a Retail-based Eye Clinic.
AB  - PURPOSE: To determine the level of adherence to the American Academy of
      Ophthalmology preferred practice pattern (PPP) guidelines for quality primary
      open-angle glaucoma (POAG) and POAG suspect (POAGS) care among retail-based
      optometrists. METHODS: Patients with a diagnosis of POAG or POAGS who
      participated in a telemedicine pilot project were included. Patients' charts were
      evaluated for 15 elements of PPP guidelines for glaucoma care. Results were
      further stratified by number of follow-up visits and diagnosis. RESULTS: Of 360
      identified patients, 10 elements were documented in over 98%. Documentation of
      the remaining 5 components was as follows: dilated fundus examination 91.1%,
      central corneal thickness (CCT) 88.6%, visual field 78.9%, gonioscopy 47.5%, and
      target intraocular pressure (IOP) 15.6%. in total, 32.8% of patients were seen
      once, whereas the remaining 67.2% had multiple visits. In patients with multiple
      visits, providers were more likely to document systemic history (100.0% vs.
      97.5%; P=0.0346), review of systems (100.0% vs. 97.5%; P=0.0346), gonioscopy
      (60.0% vs. 22.0%; P<0.001), CCT (94.2% vs. 77.1%; P<0.001), visual field (97.5%
      vs. 40.7%; P<0.001), and target IOP (22.4% vs. 1.7%; P<0.001) compared with
      single visit patients. In stratifying results by diagnosis, POAG patients more
      often received visual field testing (92.7% vs. 68.9%; P<0.001) and had an
      established target IOP (35.1% vs. 1.4%; P<0.001) compared with POAGS patients.
      CONCLUSIONS: Compliance with PPP guidelines for glaucoma care was very high for
      most elements but lower for performing dilated fundus examination, CCT, visual
      field, gonioscopy, and target IOP. This study highlights deficiencies in care
      likely to hamper the detection of glaucoma progression.

PMID- 30234751
TI  - Variation in Prostaglandin Analog Prices Paid for Through Medicare Part D.
AB  - OBJECTIVE: Determine the prices and price variation of the prostaglandin analogs
      (PGAs) used in the United States and examine their trends from 2013-2016 using
      Medicare Part D data. DESIGN: Retrospective cross-sectional study. PARTICIPANTS:
      All ophthalmologists and optometrists in all fifty states and D.C. who prescribed
      any PGA purchased through Part D from 2013 through 2016. METHODS: Outcome
      measures were calculated using Excel 2016 based off of the 2013-2016 Medicare
      Part D Prescriber Data. MAIN OUTCOME MEASURES: 2013-2016 nationwide prices of
      seven PGAs, the states with the 2016 minimum and maximum average prices, the
      standard deviations in PGA prices among the cities in each state, and the
      nationwide average of these standard deviations for 2013-2016. RESULTS: The 2016
      nationwide prices of 30-day supplies of bimatoprost, latanoprost, Lumigan,
      Travatan Z, travoprost, Xalatan, and Zioptan in 2016 were: $107.90+/-25.19,
      $10.16+/-1.52, $167.30+/-17.66, $171.36+/-19.44, $92.53+/-15.14, $153.41+/-15.16,
      and $162.75+/-13.22 respectively. Each drug's standard deviation in city prices
      within each state averaged nationwide for 30-day supplies in 2016 were $10.89,
      $1.44, $16.68, $17.23, $10.30, $10.07, and $9.48 respectively. Spending on these
      drugs totaled $861,180,924 in 2016. There was less price variation within each
      state as compared to the whole country. No substantial decreases in price
      variation exist for any drug from 2013-2016. CONCLUSIONS: There is substantial
      variation in PGA prices when purchased by Medicare Part D enrollees across the
      United States and within each state itself. Simultaneously, the prices and total
      expenditure on these medications are increasing yearly. Physicians should be
      cognizant of this price variation for these expensive and chronically used drugs
      and should educate patients to optimize their Part D supplemental plan.

PMID- 30234752
TI  - 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task
      Force for the management of arterial hypertension of the European Society of
      Cardiology and the European Society of Hypertension: The Task Force for the
      management of arterial hypertension of the European Society of Cardiology and the
      European Society of Hypertension.
AB  - : Document reviewers: Guy De Backer (ESC Review Co-ordinator) (Belgium), Anthony
      M. Heagerty (ESH Review Co-ordinator) (UK), Stefan Agewall (Norway), Murielle
      Bochud (Switzerland), Claudio Borghi (Italy), Pierre Boutouyrie (France), Jana
      Brguljan (Slovenia), Hector Bueno (Spain), Enrico G. Caiani (Italy), Bo Carlberg
      (Sweden), Neil Chapman (UK), Renata Cifkova (Czech Republic), John G. F. Cleland
      (UK), Jean-Philippe Collet (France), Ioan Mircea Coman (Romania), Peter W. de
      Leeuw (The Netherlands), Victoria Delgado (The Netherlands), Paul Dendale
      (Belgium), Hans-Christoph Diener (Germany), Maria Dorobantu (Romania), Robert
      Fagard (Belgium), Csaba Farsang (Hungary), Marc Ferrini (France), Ian M. Graham
      (Ireland), Guido Grassi (Italy), Hermann Haller (Germany), F. D. Richard Hobbs
      (UK), Bojan Jelakovic (Croatia), Catriona Jennings (UK), Hugo A. Katus (Germany),
      Abraham A. Kroon (The Netherlands), Christophe Leclercq (France), Dragan Lovic
      (Serbia), Empar Lurbe (Spain), Athanasios J. Manolis (Greece), Theresa A.
      McDonagh (UK), Franz Messerli (Switzerland), Maria Lorenza Muiesan (Italy), Uwe
      Nixdorff (Germany), Michael Hecht Olsen (Denmark), Gianfranco Parati (Italy),
      Joep Perk (Sweden), Massimo Francesco Piepoli (Italy), Jorge Polonia (Portugal),
      Piotr Ponikowski (Poland), Dimitrios J. Richter (Greece), Stefano F. Rimoldi
      (Switzerland), Marco Roffi (Switzerland), Naveed Sattar (UK), Petar M. Seferovic
      (Serbia), Iain A. Simpson (UK), Miguel Sousa-Uva (Portugal), Alice V. Stanton
      (Ireland), Philippe van de Borne (Belgium), Panos Vardas (Greece), Massimo Volpe
      (Italy), Sven Wassmann (Germany), Stephan Windecker (Switzerland), Jose Luis
      Zamorano (Spain).The disclosure forms of all experts involved in the development
      of these Guidelines are available on the ESC website www.escardio.org/guidelines.

PMID- 30234753
TI  - Middle aortic syndrome because of pediatric Takayasu arteritis admitted as acute
      heart failure: clinical course and therapeutic strategies.

PMID- 30234754
TI  - Isolated systolic hypertension in the young: a position paper endorsed by the
      European Society of Hypertension: Erratum.

PMID- 30234755
TI  - Albuminuria and diabetes: a question of eye and skin points of view: Erratum.

PMID- 30234756
TI  - Lower 6-MMP/6-TG Ratio May Be a Therapeutic Target in Pediatric Autoimmune
      Hepatitis.
AB  - BACKGROUND: Azathioprine (AZA) is the mainstay of maintenance therapy in
      pediatric autoimmune hepatitis (AIH). The use of thiopurines metabolites to
      individualize therapy and avoid toxicity has not, however, been clearly defined.
      METHODS: Retrospective analysis of children <=18 years diagnosed with AIH between
      January 2001 and 2016. Standard definitions were used for treatment response and
      disease flare. Thiopurine metabolite levels were correlated with the
      corresponding liver function test. RESULTS: A total of 56 children (32 girls)
      were diagnosed with AIH at a median age of 11 years (interquartile range [IQR]
      9). No difference in 6-thioguanine-nucleotide (6-TG) levels (271[IQR 251] pmol/8
      * 10 red blood cell vs 224 [IQR 147] pmol/8 * 10 red blood cell, P = 0.06) was
      observed in children in remission when compared with those who were not in
      remission. No correlation was observed between the 6-TG and alanine
      aminotransferase levels (r = -0.179, P = 0.109) or between 6-methyl
      mercaptopurine (6-MMP) and alanine aminotransferase levels (r = 0.139, P =
      0.213). The 6-MMP/6-TG ratio was significantly lower in patients who were in
      remission (2[7] vs 5 (10), P = 0.04). Using a quartile analysis, we found that
      having a ratio of <4 was significantly associated with being in remission with OR
      2.50 (95% confidence interval 1.02-6.10), P = 0.047. Use of allopurinol with low
      dose AZA in 6 children with preferential 6-MMP production brought about remission
      in 5/6 (83.3%). CONCLUSIONS: Thiopurine metabolite levels should be measured in
      patients with AIH who have experienced a loss of remission. A 6-MMP/6-TG ratio of
      <4 with the addition of allopurinol could be considered in these patients.

PMID- 30234757
TI  - Role of Incentives in Long-term Nutritional and Growth Studies in Children.
AB  - OBJECTIVES: Available published advice on use of incentives is limited and
      generally refers to short-term studies without longer follow-up, predominantly
      conducted in developed countries. We aim to summarize published information
      related to the use of incentives in long-term nutrition studies involving
      infants, children, and adolescents and the views of researchers in the field, to
      provide guidance on acceptable incentives. We conducted a literature review and a
      short online survey of researchers regarding their opinions on the use of
      incentives in paediatric long-term (follow-up) clinical studies. Responses from
      38 researchers from 14 different countries indicated that 41% had used incentives
      to increase participation and 29% to 73%, depending on child's age and type of
      procedure, thought incentives may be used to increase compliance with follow-up
      visits. A small number of respondents thought incentives would not be approved by
      national ethics boards. Based on the literature review and the survey results,
      and European Society for Paediatric Gastroenterology, Hepatology and Nutrition
      working group concluded that incentives for children and adolescents up to the
      value of 30 Euros, based on average EU income levels, may be offered as cash,
      vouchers, or age-appropriate gifts or toys, in addition to reimbursing expenses.
      Additional incentives may be offered if a study includes more burdening
      procedures, techniques that may appear frightening for younger children, or
      requires sustained participation (eg, dietary diaries or activity monitoring).
      There was agreement that it is preferable to give toys or gifts rather than money
      to younger children.

PMID- 30234758
TI  - Rapid Progression of Acute Pancreatitis to Acute Recurrent Pancreatitis in
      Children.
AB  - OBJECTIVE: Research is lacking on the natural history of acute pancreatitis (AP)
      progression to acute recurrent pancreatitis (ARP). The aim of this project was to
      study the progression from AP to ARP among pediatric patients with pancreatitis
      to better understand the presentation and natural history of pancreatitis.
      METHODS: Patients presenting with AP were included in a prospective database in
      Research Electronic Data Capture. We enrolled 115 AP patients from March 2013 -
      November 2016. Physicians completed surveys regarding clinical data for patients
      with first attack of AP. Patients were followed prospectively, with data on
      progression entered when patients presented with ARP. RESULTS: The most common
      etiologies for the first attack of AP were idiopathic (31%), toxic/drug related
      (23%), and biliary/gallstone (18%). Twenty of the 115 patients (17%) developed
      ARP during the follow up period. Seventy percent (14/20) of ARP patients
      progressed from AP to ARP within 5 months from first diagnosis. A comparison of
      patients who rapidly progressed to ARP within 3 months (n = 12) to those followed
      for more than 3 months without progression in 3 months (n = 97) revealed
      associations with a higher weight percentile for age (p = 0.045), male gender (p
      = 0.03) and presence of pancreatic necrosis during first AP attack (p = 0.004).
      Progression to ARP significantly differed by etiology group with genetics having
      the highest risk for ARP progression over time and patients with
      gallstone/biliary, viral/systemic, and obstructive (non-gallstone) having the
      lowest risk for ARP progression over time (p = 0.02). CONCLUSIONS: Most patients
      who progressed from AP to ARP progressed within five months. The presence of a
      higher weight percentile for age, male gender and pancreatic necrosis during the
      first AP attack are associated with rapid progression to ARP.

PMID- 30234759
TI  - Severe DGUOK Deficiency in Austria: A Six-Patient Series.
AB  - Mutations in the nuclear gene DGUOK, encoding deoxyguanosine kinase, cause an
      infantile hepatocerebral type of mitochondrial depletion syndrome (MDS). We
      report 6 MDS patients harboring bi-allelic DGUOK mutations, of which 3 are novel,
      including a large intragenic Austrian founder deletion. One patient was diagnosed
      with hepatocellular carcinoma aged 6mo, supporting a link between mitochondrial
      DNA depletion and tumorigenesis; liver transplantation proved beneficial with
      regard to both tumor treatment and psychomotor development.

PMID- 30234760
TI  - Diet and Exercise in Pediatric Liver Transplant Recipients: Behaviors and
      Association with Metabolic Syndrome.
AB  - OBJECTIVE: To analyze the impact of physical activity and eating behaviors on
      precursors of cardiovascular disease-including overweight/obesity, hypertension,
      low HDL, and impaired glucose tolerance-in pediatric liver transplant (LT)
      recipients and matched controls. METHOD: Cross-sectional study of pediatric LT
      recipients 8-30 years, matched to controls from NHANES. Dietary intake assessed
      with 24-hour recall. Physical activity assessed by standardized questionnaires.
      LT recipients >=12 years completed a confidential survey on alcohol consumption.
      RESULTS: LT recipients (n = 90) were 0.9-24.7 years post-transplant. LT
      recipients and controls were equally likely to consume excess carbohydrates (32%
      vs 34%) and sugar, per age and gender-specific recommended dietary intake (RDA)
      guidelines. LT recipients spent more hours sedentary or on the computer daily and
      fewer days each week physically active for >60 minutes than controls. More
      overweight/obese LT recipients spent 3+ hours at the computer than non-overweight
      LT recipients (49% vs 27%; p = 0.02). Normal weight LT recipients spent more days
      doing vigorous activity each week (median 5 days, IQR 2-6) than did the
      overweight/obese LT recipients (median 3 days, IQR 2-4; p = 0.01). Among LT
      recipients, neither dietary intake nor physical activity were consistently
      associated with measures of hypertension, glucose intolerance, or dyslipidemia.
      Among LT adolescents and young adults (n = 38), 36% reported ever consuming
      alcohol; 38% of these reported significant alcohol consumption by frequency or
      quantity. CONCLUSIONS: Additional counseling during routine post-LT care on the
      importance of physical activity and healthy diet may be useful. However, it is
      unlikely that these factors alone explain the increased prevalence of metabolic
      syndrome components in pediatric LT recipients.

PMID- 30234761
TI  - Recurrent Abdominal Pain in Children: Is Colonoscopy Indicated?
AB  - INTRODUCTION: Recurrent abdominal pain in children is common, with most
      functional in origin. Colonoscopy has sometimes been performed to exclude
      pathology but its role is unclear. Our aim therefore was to assess the diagnostic
      yield and role of colonoscopy in these children. METHODS: Retrospective review of
      consecutive colonoscopies in a tertiary pediatric hospital between November 2011
      and October 2015 was undertaken. Only those with recurrent abdominal pain as an
      indication for procedure were included. Chart review of patients with pain was
      undertaken to ensure they fulfilled Rome IV criteria. Patient demographics,
      indication for procedure, and adjunct pre-procedure tests were noted. Statistical
      analyses were performed with SPSS software. RESULTS: 652 colonoscopies were
      performed, of which 68 (10%) had abdominal pain as one of the indications; and
      was the sole indication in 15 (2%) patients. All 68 patients had pre-procedure
      serum inflammatory markers measured and 53% (36/68) had stool calprotectin.
      Positive histology was found in 10% (7/68) including Crohn disease (n = 3),
      polyps (n = 2), and microscopic colitis (n = 2). The remaining 61 patients had
      normal colonoscopy and ileocolonic biopsies. 5/36 patients had raised fecal
      calprotectin, and all had abnormal histology. Serum inflammatory markers were
      raised in 4 patients and all also had abnormal calprotectin. No patient with
      isolated abdominal pain had positive histology. Rectal bleeding was the only
      associated indication to predict abnormal histology (p = 0.019). CONCLUSIONS:
      Colonoscopy is likely not warranted in children with recurrent abdominal pain
      without bleeding, weight loss or altered bowel habit. Fecal calprotectin is
      useful in helping predict positive findings.

PMID- 30234762
TI  - Hepatic Steatosis is Prevalent following Orthotopic Liver Transplantation in
      Children with Cystic Fibrosis.
AB  - OBJECTIVES: Systematic study of allograft liver histology in children undergoing
      orthotopic liver transplantation (LT) for cystic fibrosis-related liver disease
      (CFLD). METHODS: Retrospective clinicopathologic review of explants and allograft
      liver biopsies from 13 children and adolescents with CFLD. RESULTS: In this
      study, the median age at LT for CFLD was 15.7 years. Notably, 10 of 13 (77%) CF
      explants had >5% steatosis and 8 of 13 (61.5%) demonstrated variable fibrosis.
      The median age, gender, type of transplant (liver vs liver-lung), pancreatic
      insufficiency (PI) status, BMI%ile, genotype and prevalence of diabetes were
      comparable in those with and without explant steatosis. More than half of
      allograft biopsies showed significant steatosis (17/31, 54.8%) and lobular
      inflammation (16/31, 51.6%). Hepatocyte ballooning was less frequent (5/31,
      16.1%). Overall, 6 patients (46.2%) had allograft steatosis that worsened over
      time in 2 patients (33%). None had advanced fibrosis (>=stage 3). Patients with
      allograft steatosis had significantly more biopsies, were more likely to be
      'liver only' recipients, had a shorter interval since transplant and higher
      BMI%ile (though <85). Patients without explant steatosis never demonstrated
      allograft steatosis, while 60% of patients with explant steatosis (n = 6)
      developed varying degrees of allograft steatosis. The degree of explant steatosis
      did not predict its severity in allografts (p = 0.3). CONCLUSION: This is the
      first study highlighting the development of allograft steatosis in CF patients.
      Our findings suggest that allograft steatosis in patients with CF may be related
      to pre-existing steatosis in native livers, regardless of other risk factors and
      may have implications on patient management and long-term graft/patient survival.

PMID- 30234763
TI  - Innovations in Occupational Health Care Delivery Can Prevent Entry into Permanent
      Disability: 8-Year Follow-up of the Washington State Centers for Occupational
      Health and Education.
AB  - BACKGROUND: Long-term work disability is known to have an adverse effect on the
      nation's labor force participation rate. To reduce long-term work disability, the
      Washington State Department of Labor and Industries established a quality
      improvement initiative that created 2 pilot Centers of Occupational Health and
      Education (COHE). OBJECTIVES: To document the level of work disability in a
      sample of injured workers with musculoskeletal injuries and to examine (8-y) work
      disability outcomes associated with the COHE health care model. RESEARCH DESIGN:
      Prospective nonrandomized intervention study with nonequivalent comparison group
      using difference-in-difference regression models. SUBJECTS: Intervention group
      represents 18,790 workers with musculoskeletal injuries treated by COHE
      providers. Comparison group represents 20,992 workers with similar injuries
      treated within the COHE catchment area by non-COHE providers. MEASURES: Long-term
      disability outcomes include: (1) on disability 5 years after injury; (2) received
      a state pension for total permanent disability; (3) received total disability
      income support through the Social Security Disability Insurance program; or (4) a
      combined measure including any one of the 3 prior measures. RESULTS: COHE
      patients had a 30% reduction in the risk of experiencing long-term work
      disability (odds ratio=0.70, P=0.02). The disability rate (disability days per
      1000 persons) over the 8-year follow-up for the intervention and comparison
      groups, respectively, was 49,476 disability days and 75,832 disability days.
      CONCLUSIONS: Preventing long-term work disability is possible by reorganizing the
      delivery of occupational health care to support effective secondary prevention in
      the first 3 months following injury. Such interventions may have promising
      beneficial effects on reversing the nation's progressively worsening labor force
      participation rate.

PMID- 30234764
TI  - The Prevalence of Culture Change Practice in US Nursing Homes: Findings From a
      2016/2017 Nationwide Survey.
AB  - BACKGROUND AND OBJECTIVES: Given the dynamic nursing home (NH) industry and
      evolving regulatory environment, depiction of contemporary NH culture-change
      (person/resident-centered) care practice is of interest. Thus, we aimed to
      portray the 2016/2017 prevalence of NH culture change-related processes and
      structures and to identify factors associated with greater practice prevalence.
      RESEARCH DESIGN AND METHODS: We administered a nationwide survey to 2142 NH
      Administrators at NHs previously responding to a 2009/2010 survey. Seventy-four
      percent of administrators (1583) responded (with no detectable nonresponse bias)
      enabling us to generalize (weighted) findings to US NHs. From responses, we
      created index scores for practice domains of resident-centered care, staff
      empowerment, physical environment, leadership, and family and community
      engagement. Facility-level covariate data came from the survey and the
      Certification and Survey Provider Enhanced Reporting system. Ordered logistic
      regression identified the factors associated with higher index scores. RESULTS:
      Eighty-eight percent of administrators reported some facility-level involvement
      in NH culture change, with higher reported involvement consistently associated
      with higher domain index scores. NHs performed the best (82.6/100 weighted
      points) on the standardized resident-centered care practices index, and had the
      lowest scores (54.8) on the family and community engagement index. Multivariable
      results indicate higher index scores in NHs with higher leadership scores and in
      states having Medicaid pay-for-performance with culture change-related quality
      measures. CONCLUSIONS: The relatively higher resident-centered care scores
      (compared with other domain scores) suggest an emphasis on person-centered care
      in many US NHs. Findings also support pay-for-performance as a potential
      mechanism to incentivize preferred NH practice.

PMID- 30234765
TI  - Lack of Health Insurance Associated With Lower Probability of Head Computed
      Tomography Among United States Traumatic Brain Injury Patients.
AB  - BACKGROUND: Uninsured traumatic brain injury (TBI) patients have higher mortality
      than their insured counterparts. One possible reason is disparities in receipt of
      appropriate diagnostic imaging. OBJECTIVE: Examine the association between lack
      of insurance and use of diagnostic imaging. RESEARCH DESIGN: This is a
      retrospective cohort study. SUBJECTS: All adult patients admitted with severe
      (AIS>4 and GCS<15) TBI, in the National Trauma Data Bank 2010-2015. MEASURES:
      Primary outcome was receipt of head computed tomography (CT) and number of CT
      scans received. Secondary outcomes included head x-ray, angiography, or magnetic
      resonance imaging. Patients were classified as uninsured if their payment method
      was self-pay or not billed. RESULTS: Of 59,540 patients meeting inclusion
      criteria, 18.9% were uninsured. After adjusting for demographic, clinical, and
      facility characteristics, compared with patients with any insurance, 4.47 per 100
      (95% confidence interval, 1.60-7.34) fewer uninsured patients had a head CT, with
      uninsured patients receiving 13% (95% confidence interval, 3-21) fewer head CTs.
      There were no differences in x-ray, angiography, or magnetic resonance imaging
      receipt. CONCLUSIONS: Findings suggest lower receipt of guideline-indicated head
      CT among uninsured TBI patients. Mechanisms could include unconscious provider
      bias or institutional financial constraints. Further research is warranted to
      elucidate mechanisms and assess mediation by diagnostic imaging use of the
      insurance-mortality association.

PMID- 30234767
TI  - Insurance Coverage and Utilization Improve for Latino Youth but Disparities by
      Heritage Group Persist Following the ACA.
AB  - OBJECTIVE: Latino youth experience worse access to and utilization of health care
      compared with non-Latino "white" youth, with inequities persisting following the
      implementation of the Affordable Care Act (ACA). To better understand these
      disparities, we examine changes in youth's access and utilization associated with
      the ACA for different Latino heritage groups relative to whites. STUDY DESIGN: We
      use 6 years (2011-2016) of National Health Interview Survey data to examine
      Latino youth's insurance coverage and health care utilization by heritage group,
      nativity, and parental language. The dependent measures of utilization included
      well-child, emergency department, and physician visits. We used multivariable
      logistic regression models to estimate the odds of each dependent measure and
      interacted heritage group and time period [2011-2013 (pre-ACA) versus 2014-2016
      (post-ACA)] to examine how changes associated with the ACA varied by group.
      RESULTS: Insurance coverage and well-child visits improved among youth overall
      following implementation of the ACA. Although Mexican and Central or South
      American youth experienced the largest absolute increase in coverage, they still
      had high levels of uninsurance post-ACA (9.9% and 9.1%, respectively).
      Disparities in coverage between Puerto Rican and white youth improved, while
      disparities in well-child visits between Mexican and white youth worsened. Little
      to no movement was observed in disparities by nativity and parental language.
      CONCLUSIONS: Most disparities in insurance and utilization across Latino heritage
      groups and white youth persisted post-ACA despite significant gains within
      groups. Although disparities for Puerto Rican youth have improved, Mexican and
      Central or South American youth continue to experience disparities.

PMID- 30234766
TI  - The Relative Ability of Comorbidity Ascertainment Methodologies to Predict In
      Hospital Mortality Among Hospitalized Community-acquired Pneumonia Patients.
AB  - BACKGROUND: Despite widespread use of comorbidities for population health
      descriptions and risk adjustment, the ideal method for ascertaining comorbidities
      is not known. We sought to compare the relative value of several methodologies by
      which comorbidities may be ascertained. METHODS: This is an observational study
      of 1596 patients admitted to the University of Chicago for community-acquired
      pneumonia from 1998 to 2012. We collected data via chart abstraction,
      administrative data, and patient report, then performed logistic regression
      analyses, specifying comorbidities as independent variables and in-hospital
      mortality as the dependent variable. Finally, we compared area under the curve
      (AUC) statistics to determine the relative ability of each method of comorbidity
      ascertainment to predict in-hospital mortality. RESULTS: Chart review (AUC, 0.72)
      and administrative data (Charlson AUC, 0.83; Elixhauser AUC, 0.84) predicted in
      hospital mortality with greater fidelity than patient report (AUC, 0.61).
      However, multivariate logistic regression analyses demonstrated that individual
      comorbidity derivation via chart review had the strongest relationship with in
      hospital mortality. This is consistent with prior literature suggesting that
      administrative data have inherent, paradoxical biases with important implications
      for risk adjustment based solely on administrative data. CONCLUSIONS: Although
      comorbidities derived through administrative data did produce an AUC greater than
      chart review, our analyses suggest a coding bias in several comorbidities with a
      paradoxically protective effect. Therefore, chart review, while labor and
      resource intensive, may be the ideal method for ascertainment of clinically
      relevant comorbidities.

PMID- 30234768
TI  - Evaluating the Impact of Eliminating Copayments for Tobacco Cessation
      Pharmacotherapy.
AB  - OBJECTIVES: We examined the impact of the Affordable Care Act-mandated
      elimination of tobacco cessation pharmacotherapy (TCP) copayments on patient use
      of TCP, overall and by income. METHODS: Electronic health record data captured
      any and combination (eg, nicotine gum plus patch) TCP use among adult smokers
      newly enrolled in Kaiser Permanente Northern California (KPNC). KPNC eliminated
      TCP copayments in 2015. We included current smokers newly enrolled in the first 6
      months of 2014 (before copayment elimination, N=16,199) or 2015 (after
      elimination, N=16,469). Multivariable models estimated 1-year changes in rates of
      any TCP fill, and of combination TCP fill, and tested for differences by income
      (<$50k, $50>=75k, >=$75k). Through telephone surveys in 2016 with a subset of
      smokers newly enrolled in 2014 (n=306), we assessed barriers to TCP use, with
      results stratified by income. RESULTS: Smokers enrolled in KPNC in 2015 versus
      2014 were more likely to have a TCP fill (9.1% vs. 8.2%; relative risk, 1.19; 95%
      confidence interval, 1.11-1.27), and combination TCP fill, among those with any
      fill (42.3% vs. 37.9%; relative risk, 1.12; 95% confidence interval, 1.02-1.23);
      findings were stronger for low-income smokers. Low-income patients (<$50k) were
      less likely to report that clinicians discussed smoking treatments with them
      (58%) compared with higher income smokers ($50>=75k, 67%; >=$75k, 83%), and were
      less aware that TCP was free (40% vs. 53% and 69%, respectively, P-values<0.05).
      CONCLUSIONS: The Affordable Care Act's copayment elimination was associated with
      a modest increase in TCP use and a greater effect among low-income smokers.
      Uptake may have been enhanced if promoted to patients directly and via providers.

PMID- 30234769
TI  - The Impact of Public Performance Reporting on Market Share, Mortality, and
      Patient Mix Outcomes Associated With Coronary Artery Bypass Grafts and
      Percutaneous Coronary Interventions (2000-2016): A Systematic Review and Meta
      Analysis.
AB  - OBJECTIVE: Public performance reporting (PPR) of coronary artery bypass graft
      (CABG) and percutaneous coronary intervention (PCI) outcomes aim to improve the
      quality of care in hospitals, surgeons and to inform consumer choice. Past CABG
      and PCI studies have showed mixed effects of PPR on quality and selection. The
      aim of this study was to undertake a systematic review and meta-analysis of the
      impact of PPR on market share, mortality, and patient mix outcomes associated
      with CABG and PCI. METHODS: Six online databases and 8 previous reviews were
      searched for the period 2000-2016. Data extraction, quality assessment,
      systematic critical synthesis, and meta-analysis (where possible) were carried
      out on included studies. RESULTS: In total, 22 relevant articles covering
      mortality (n=19), patient mix (n=14), and market share (n=6) outcomes were
      identified. Meta-analyses showed that PPR led to a near but not significant
      reduction in short-term mortality for both CABG and PCI. PPR on CABG showed a
      positive effect on market share for hospitals (3 of 6 studies) and low-performing
      surgeons (2 of 2 studies). Five of 6 PCI studies found that high-risk patients
      were less likely to be treated in States with PPR. CONCLUSIONS: There is some
      evidence that PPR reduces mortality rates in CABG/PCI-treated patients. The
      significance of there being no strong evidence, in the period 2000-2016, should
      be considered. There is need for both further development of PPR practice and
      further research into the intended and unintended consequences of PPR.

PMID- 30234770
TI  - A brief submaximal isometric exercise test 'unmasks' systolic and diastolic
      masked hypertension.
AB  - OBJECTIVES: An exaggerated blood pressure (BP) response during dynamic exercise
      testing has been proposed as an additional screening tool to identify systolic
      masked hypertension (masked-HYP). However, masked-HYP in young people is often
      characterized by an elevated DBP. Static/isometric exercise elicits augmented
      sympathetic stimulation causing greater increases in both SBP and DBP than
      dynamic exercise. AIMS: To examine whether individuals with masked-HYP exhibit
      exaggerated BP responses during a submaximal handgrip vs. normotensive
      individuals and individuals with sustained hypertension (true-HYP), and the
      possible associations of exercise BP with total peripheral resistance (TPR),
      central/aortic BP, and 24-h-ambulatory BP (24-h BP). METHODS: Eighty-six
      participants [untreated, newly diagnosed, masked-HYP (n = 27), true-HYP (n = 31),
      and normotensive individuals (n = 28); 46.3 +/- 10.7 years], following evaluation
      of office BP, central/aortic BP, pulse wave velocity, carotid intima-media
      thickness, echocardiocardiography, and 24-h BP, underwent a 3-min handgrip (30%
      maximal voluntary contraction) with beat-by-beat BP and hemodynamics assessment
      (Finapres Medical Systems). RESULTS: Despite similar baseline-BP in masked-HYP
      and normotensive individuals, during exercise masked-HYP exhibited a markedly
      greater (P < 0.01) SBP and DBP vs. normotensive individuals, and similar BP to
      true-HYP. TPR significantly increased (P < 0.001) during exercise, in masked-HYP
      and true-HYP. The exaggerated BP responses in masked-HYP were evident from the
      1st minute of exercise and correlated (P < 0.05) with central/aortic-BP, aortic
      stiffness, 24-h BP, day-BP, night-time-BP, and interventricular septum thickness.
      CONCLUSION: During handgrip, masked-HYP exhibited exaggerated BP and TPR
      responses, similar to those of true-HYP. These responses were evident from the
      1st minute of exercise and correlated with 24-h BP, suggesting that systolic and
      diastolic masked-HYP can be 'unmasked' during a brief, submaximal, handgrip test.

PMID- 30234771
TI  - Difference in SBP between arms is a predictor of chronic kidney disease
      development in the general Korean population.
AB  - OBJECTIVE: An increased inter-arm SBP difference (IASBPD) is associated with
      mortality and cardiovascular events, as well as peripheral vascular disease,
      which is attributed to subclavian stenosis. The aim of the present study was to
      investigate the association between the IASBPD and incident chronic kidney
      disease (CKD) in the Korean population. METHODS: A retrospective cohort study was
      performed on 8780 Korean adults without baseline CKD. The bilateral blood
      pressure was measured sequentially and repeatedly at the first visit. IASBPD was
      defined as a BP at least 15 mmHg according to the National Institutes for Health
      and Clinical Excellence guidelines, and CKD was defined as an estimated
      glomerular filtration rate less than 60 ml/min per 1.73 m. We assessed the value
      of IASBPD to predict the incidence of CKD and investigated cardiovascular
      disease, including coronary heart disease and stroke. RESULTS: Over a mean follow
      up period of 8.5 years, 96 of 581 (16.5%) patients in the IASBPD group and 1037
      of 8199 (12.6%) patients in the non-IASBPD group developed incident CKD. Compared
      with the non-IASBPD, an IASBPD was associated with incident CKD [hazard ratio
      (HR): 1.336, 95% confidence interval (CI): 1.08-1.65, P = 0.007]. After adjusting
      for potential confounders, including age, sex, hypertension, diabetes, and
      obesity, we found that the hazard ratio was also robust (hazard ratio 1.275, 95%
      CI 1.03-1.58, P = 0.024). CONCLUSION: Increased IASBPD is an independent
      predictor of incident CKD in the general population.

PMID- 30234772
TI  - Normotensive patients with obstructive sleep apnoea: changes in 24-h ambulatory
      blood pressure monitoring with continuous positive airway pressure treatment.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) treatment reduces blood
      pressure (BP) in obstructive sleep apnoea (OSA) and hypertensive patients, but
      there is a lack of data about the effects of CPAP on the BP in normotensive
      patients. OBJECTIVE: The aim of the study was to evaluate BP changes in
      normotensive OSA individuals receiving CPAP treatment. METHODS: We selected 131
      normotensive outpatients with an apnoea/hypopnoea index (AHI) greater than 15
      events/hour who required CPAP treatment. All patients underwent a sleep study and
      24-h ambulatory BP monitoring (ABPM) at baseline and after 6 months. In addition,
      the patients were assessed for the presence of baseline masked hypertension,
      defined as office BP less than 140/90 mmHg and increased BP on 24-h ABPM (mean 24
      h BP >=130/80 mmHg). RESULTS: After 6 months of CPAP treatment, a mild reduction
      in all 24-h ABPM variables was observed, but only the mean 24-h DBP [-1.39 mmHg,
      95% confidence interval (95% CI), -2.50 to -0.27], mean daytime DBP (-1.39 mmHg,
      95% CI -2.56 to -0.22) and the mean 24-h ambulatory BP (-1.80 mmHg, 95% CI, -3.16
      to -0.44) reached statistical significance. The reduction was primarily due to BP
      changes in individuals with masked hypertension who displayed a mean BP reduction
      of -4.78 mmHg (-7.25 to -2.30 mmHg). Consistent with a circadian BP pattern, a
      reduction in mean nocturnal BP of -4.73 mmHg (-7.39 to -2.06 mmHg) was observed
      at 6 months in nondippers; in contrast, the mean nocturnal BP in dippers
      increased by 2.61 mmHg (0.60-4.62 mmHg). CONCLUSION: Our findings suggest that
      the CPAP effects may be different in normotensive outpatients depending on the
      presence of undiagnosed masked hypertension and the dipping pattern. Therefore,
      it is important to consider measuring ABPM in this type of patient.

PMID- 30234773
TI  - Different effects of antihypertensive treatment on office and ambulatory blood
      pressure: a meta-analysis.
AB  - OBJECTIVE: Office and ambulatory blood pressure (BP) measurements are the main
      techniques to detect the effects of antihypertensive treatments in clinical
      trials, but the treatment-induced changes in these BP values can differ markedly.
      We performed a meta-analysis of clinical trials to quantify these differences and
      identified some of the associated factors. METHODS: We conducted a MEDLINE search
      for randomized clinical trials (RCTs) on hypertensive patients treated with at
      least one antihypertensive drug that reported changes in both office and 24-h BP.
      Random-effects models were fitted to estimate the summary of the difference
      between the changes as quantified by either technique. The I and Cochrane's Q
      statistics were calculated to evaluate the heterogeneity between studies.
      RESULTS: A total of 52 studies were included in our meta-analysis with about 9500
      patients. The summary estimate Delta of SBP and DBP was -6.5 (95% confidence
      interval: -7.5 to -5.6) and -3.3 (95% confidence interval, -3.9 to -2.7),
      respectively. The difference was independent on the treatment duration and use of
      mono or combination treatment but for SBP it varied with the different treatment
      types in monotherapy, and it was greater in relation to baseline office BP and
      age. Allowing for the placebo effect also reduced the difference. Absolute on
      treatment BP values were at target for either pressure and the rate of controlled
      hypertensive individuals was similar (around one-third) for either measuring
      approach. CONCLUSION: Our meta-analysis confirms that overall treatment-induced
      reduction is markedly greater for office BP than for 24-h BP, but it also shows
      that the quantitative relationship between these two measuring approaches varies
      with demographic, clinical and therapeutic conditions as well as in relation to
      placebo correction.

PMID- 30234774
TI  - Optimal SBP targets in routine clinical care.
AB  - OBJECTIVE: Compare outcomes of intensive treatment of SBP to less than 120 mmHg
      versus standard treatment to less than 140 mmHg in the US clinical Systolic Blood
      Pressure Intervention Trial (SPRINT) with similar hypertensive patients managed
      in routine primary care in the United Kingdom. METHODS: Hypertensive patients
      aged 50-90 without diabetes or chronic kidney disease (CKD) were selected in
      SPRINT and The Health Improvement Network (THIN) database. Patients were enrolled
      in 2010-2013 and followed-up to 2015 (SPRINT N = 4112; THIN N = 8631). Cox's
      proportional hazards regressions were fitted to estimate the hazard of all-cause
      mortality or CKD (main adverse effect) associated with intensive treatment,
      adjusted for sex, age, ethnicity, smoking, blood pressure, cardiovascular
      disease, aspirin, statin, number of antihypertensive drugs at baseline, change in
      number of antihypertensive drugs at trial entry, and clinical site. RESULTS:
      Almost half of the patients had intensive treatment (43-45%). In SPRINT,
      intensive treatment was associated with a decreased hazard of mortality of 0.63
      (0.43-0.92), while in THIN with an increased hazard of 1.66 (1.28-2.15). In THIN,
      this effect was time-dependent. Intensive treatment was associated with an
      increased hazard of CKD of 2.67 (1.74-4.11) in SPRINT and 1.35 (1.08-1.70) in
      THIN. In THIN, this effect differed by the number of antihypertensive drugs
      prescribed at baseline. CONCLUSION: It appears that intensive treatment of SBP
      may be harmful in the general population where all have access to routine
      healthcare as with the UK National Health Services, but could be beneficial in
      high-risk patients who are closely monitored.This is an open access article
      distributed under the Creative Commons Attribution License 4.0 (CCBY), which
      permits unrestricted use, distribution, and reproduction in any medium, provided
      the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

PMID- 30234775
TI  - Intra-arterial analysis of the best calibration methods to estimate aortic blood
      pressure.
AB  - OBJECTIVE: Estimation of aortic blood pressure (BP) requires peripheral BP
      waveform calibration. Mean arterial pressure (MAP)/DBP calibration is purported
      to estimate aortic BP more accurately than SBP/DBP calibration. However, this is
      based on inaccurate cuff calibration. Thus, direct comparisons of each
      calibration method using intra-arterial BP are required to confirm this, and was
      the aim of this study. METHODS: Ascending aortic, brachial and radial artery
      intra-arterial BPs were measured among 107 patients (61.9 +/- 10.0 years, 70%
      men) undergoing coronary angiography. Radial waveforms were calibrated with
      brachial SBP/DBP and brachial MAP/DBP to directly test the accuracy of estimated
      aortic SBP (derived using a commercial device) from each calibration compared
      with intra-arterial aortic SBP. Estimated aortic BP accuracy from aortic MAP/DBP,
      brachial and radial SBP/DBP calibrations of peripheral waveforms was also tested
      (six calibration methods in total; all using intra-arterial BP). RESULTS:
      Estimated aortic SBP from brachial MAP/DBP calibration of radial waveforms had a
      significantly smaller mean difference than from brachial SBP/DBP calibration (
      0.7 +/- 7.5 mmHg versus -6.9 +/- 7.3 mmHg, P < 0.0001 for difference). Of the
      other calibration methods, estimated aortic SBP was most accurate from aortic
      MAP/DBP calibration of radial waveforms (-1.8 +/- 5.0 mmHg, P = 0.00023).
      However, for all calibration methods, aortic-to-brachial artery and/or brachial
      to-radial artery SBP amplification had a major influence on estimated aortic SBP.
      CONCLUSION: Brachial and aortic MAP/DBP were confirmed as the best calibration
      methods to estimate aortic SBP, but irrespective of calibration method, accuracy
      was significantly influenced by the level of SBP amplification. Thus, improved
      accuracy of estimated aortic SBP should be possible by closer consideration of
      SBP amplification or individual waveform characteristics that differ according to
      the level of SBP amplification.

PMID- 30234776
TI  - Frequency of achieving a 'fit' cardiorespiratory fitness level and hypertension:
      a cohort study.
AB  - OBJECTIVES: Although maintaining cardiorespiratory fitness is encouraged to
      reduce the risk of hypertension, the level at, and length of time for which,
      individuals need to maintain fitness remains unclear. We examined the association
      between the frequency of achieving the recommended fitness levels of the
      'Physical Activity Reference for Health Promotion 2013' and the risk of
      hypertension among Japanese men. METHODS: This cohort study was conducted in 6653
      men without hypertension enrolled in 1986. Whether the participants' fitness
      level was equal to or exceeded the reference value (fit) or not (unfit) was
      determined. The frequency of achieving the recommended fitness level was
      calculated by counting the number of times the fitness level was achieved in 1980
      through 1986. Incident hypertension was defined as the first visit with a SBP/DBP
      of at least 140/90 mmHg or self-reported antihypertensive medication use and was
      evaluated during annual health examinations from 1986 until 2009. RESULTS: During
      the follow-up period, 3630 men developed hypertension. The multivariable-adjusted
      hazard ratios (95% confidence interval) for incident hypertension comparing men
      with fit versus unfit at baseline was 0.79 (0.74-0.85). Moreover, the frequency
      of achieving the recommended fitness level was inversely associated with the
      incidence of hypertension. The risk of hypertension was lower among those who
      achieved three or more of the recommended levels (0.72 for three times to 0.62
      for seven times). CONCLUSION: Achieving the fitness level recommended in the
      Japanese guideline three or more times during a 6-year period can be beneficial
      for the risk reduction of hypertension.

PMID- 30234777
TI  - Wave reflections in hypertension: role of sex, metabolic, and ethnic factors.
AB  - OBJECTIVES: Although the links between pulsatile hemodynamics and age are widely
      acknowledged in hypertension, the interactions of sex, ethnicity, and metabolic
      factors with hemodynamic parameters remain largely unknown. We investigated the
      effects of body weight, glycemia, and cholesterolemia on the carotid augmentation
      index (CAI) and potential changes over time, with particular focus on the roles
      of sex and ethnicity. METHODS: Baseline (V1) and repeat (V2) measurements (at
      ~1.7 years) of wave reflections (calculated from CAI), brachial and carotid pulse
      pressure, and heart rate were assessed in 2530 normotensive and hypertensive men
      and women living in Paris but born in either France, Africa, or Asia. RESULTS: At
      V1, and in comparison with French-born individuals, African-born individuals had
      significantly higher CAI, cardiovascular risk, and body weight, whereas Asian
      born individuals had similar CAI but lower body weight, and higher cardiovascular
      risk, triglyceridemia, and heart rate. Stepwise multiple regression showed
      similar effects of cholesterolemia on CAI in all populations, whereas only French
      born individuals (insulin-resistant men and women) showed associations between
      hyperglycemia and potential CAI dysfunction. Repeat (V2) measurements highlighted
      significant interactions (P < 0.008) of sex and ethnicity with changes in CAI
      over time. In men, CAI changes did not differ as a function of ethnicity, whereas
      in African-born women, they were lesser than those of Asian-born (P < 0.03) and
      French-born (P < 0.02) women. CONCLUSION: In the French-born population, CAI
      changes are affected by diabetes and possibly insulin-resistance, independently
      of sex. In African-born and Asian-born populations, CAI is sex-specific. Elevated
      CAI in African-born women calls for close monitoring of cardiovascular risk.

PMID- 30234778
TI  - Arterial stiffness and hypertension status in Afro-Caribbean men.
AB  - OBJECTIVE: African ancestry individuals are at high risk for hypertensive
      cardiovascular disease (CVD) and could benefit from early detection of arterial
      stiffening. We tested the association between the 2017 ACC/AHA hypertension
      categorizations, which include new blood pressure (BP) cutoffs and a definition
      for elevated BP, and arterial stiffness in 772 Afro-Caribbean men aged 50+ years
      (mean 64 years). METHODS: Arterial stiffness was assessed by brachial-ankle pulse
      wave velocity (PWV) using a waveform analyzer. Hypertension groups were based on
      the 2017 ACC/AHA guidelines and by pharmacologic control status. Multiple
      linear/logistic regression was used to determine the association of PWV with BP
      and hypertension. RESULTS: Mean (SD) PWV was 1609 (298) cm/s and was
      independently correlated with age, SBP, pulse, diabetes, height, and alcohol
      intake (all P < 0.02). After adjusting for these, in men aged at least 65 years,
      those with stage 1 or uncontrolled stage 2 hypertension had significantly greater
      PWV than all other groups (all P < 0.05). Men with controlled hypertension had
      similar PWV to those with elevated BP (P = 0.7); however, this was significantly
      greater than men with normal BP (all P < 0.05). Patterns were similar, but with
      smaller effect sizes, in men aged less than 65 years (all P < 0.05 except
      controlled hypertension versus elevated or normal BP were not significant).
      CONCLUSION: In these high-risk Afro-Caribbeans: stage 1 hypertension is
      associated with increased PWV, which supports the new guidelines; and,
      pharmacologic control appears to partially protect men from increased PWV.
      Longitudinal studies are needed to determine optimal PWV and timing of
      antihypertensive treatment for preventing future CVD.

PMID- 30234780
TI  - Elastic properties of ascending aorta and ventricular-arterial coupling in women
      with previous pregnancy complicated by HELLP syndrome.
AB  - OBJECTIVE: To compare the elastic properties of the ascending aorta and
      ventricular-arterial coupling (VAC) in women with a previous pregnancy
      complicated by hemolysis, elevated liver enzymes, and low platelets (HELLP)
      syndrome, women who experienced preeclampsia, and healthy controls. METHODS:
      Women with a history of preeclampsia (n = 60) or HELLP syndrome (n = 49) and
      matched healthy controls (n = 60) underwent transthoracic echocardiography at 6
      months to 4 years after delivery. Aortic M-mode and tissue Doppler imaging (TDI)
      parameters were measured. Aortic diameters were assessed at end-diastole at four
      levels: Valsalva sinuses, sinotubular junction, tubular tract, and aortic arch.
      Aortic compliance, distensibility, stiffness index, Peterson's elastic modulus,
      pulse-wave velocity, and M-mode strain were calculated using standard formulae.
      Aortic expansion velocity, early and late diastolic retraction velocities, and
      peak systolic tissue strain (TDI-epsilon) were determined. VAC was defined as the
      ratio between aortic elastance (Ea) and left ventricular end-systolic elastance
      (Ees). All women were free from cardiovascular risk factors. RESULTS: Women with
      a history of HELLP syndrome showed larger aortas than those with previous
      preeclampsia or controls, probably related to a higher blood pressure. Aortic
      elastic properties, including Ea, were similar between HELLP and preeclampsia
      groups, even comparing cases with early-onset preeclampsia and HELLP. In
      contrast, Ees was more impaired in the HELLP group than in the other two.
      Consequently, about one-quarter of women who experienced HELLP syndrome had a
      pathological VAC, whereas only 5% of previously preeclamptic patients did.
      Multivariate analysis confirmed the association between HELLP syndrome and VAC,
      whereas other parameters including aortic compliance, distensibility, stiffness
      index, and elastic modulus are linked only to gestational age at preeclampsia
      onset, ad also Ea and Ees did. CONCLUSIONS: We found a significant overlap
      between the aortic elastic properties in women with a history of preeclampsia and
      those with a previous HELLP syndrome, suggesting a common pathophysiologic
      pathway. However, women who experienced HELLP syndrome showed a higher blood
      pressure than other cases and controls, probably determining larger aortas. In
      addition, VAC was more altered in the HELLP group than in the others because of a
      higher Ea and a lower Ees.

PMID- 30234779
TI  - The influence of the North Atlantic oscillation index on arterial blood pressure.
AB  - AIM: to detect the complex association between arterial blood pressure (BP) and
      air temperature, atmospheric pressure, relative humidity, wind speed, and North
      Atlantic oscillation (NAO) indices. METHODS: Data were obtained from the survey
      performed in the framework of the international Health, Alcohol and Psychosocial
      Factors in Eastern Europe study. The number of individuals used in the models or
      other analysed groups was 7077. The association between environmental variables
      and SBP and DBP were evaluated by applying the multiple regression analysis,
      adjusting for health-related and weather variables. RESULTS: More than one-half
      (58.7%) of the respondents had high BP, and 39.4% of the respondents had taken
      drugs for high BP during the last 2 weeks. Among the respondents, the mean SBP
      and DBP were 141.6 +/- 22.2 and 90.4 +/- 12.5 mmHg, respectively. An increase in
      SBP was associated with the presence of a lower relative humidity, and a higher
      wind speed and extreme atmospheric pressure with a lag of 2 days. During the
      period of spring-autumn, continuous NAO indices on the same day and a positive
      NAO on the same and on 2 previous days were negatively associated with the SBP
      value. A positive NAO was associated (P = 0.001) with a decrease in SBP by 1.7
      mmHg in all participants, by 2.30 mmHg in physically active participants, and by
      3.62 mmHg in the elderly, as compared with a negative NAO. CONCLUSION: These
      results provided new evidence that the NAO index may be affect the value of SBP
      and DBP in the elderly during the period of spring-autumn.

PMID- 30234781
TI  - Hypermethylation of delta-like homolog 1/maternally expressed gene 3 loci in
      human umbilical veins: insights into offspring vascular dysfunction born after
      preeclampsia.
AB  - BACKGROUND: Increasing epidemiological studies have confirmed the association
      between maternal preeclampsia and elevated blood pressure in their offspring.
      Though case-control or cohort studies have demonstrated long-term outcomes for
      the offspring of preeclampsia, it is still a question that how these changes were
      caused by genetic reasons or by preeclampsia itself. OBJECTIVE: In our study, we
      explored the potential epigenetic regulation of delta-like homolog 1-maternally
      expressed gene 3 (DLK1-MEG3) region in human umbilical vein endothelial cells
      (HUVECs), and its connection with endothelium-derived factors. STUDY DESIGN: We
      recruited 58 singletons born with spontaneous conception (control group) and 67
      singletons whose mother with preeclampsia (preeclampsia group), and detected the
      infants' blood pressure and growth development index. To explore the potential
      mechanism, we did real-time PCR to test DLK1-MEG3 imprinted genes and endothelium
      derived factors. ELISA confirmed the protein secretion changes between two
      groups. In addition to confirm epigenetic alteration in preeclampsia HUVEC, we
      performed pyro-sequencing to detect methylation status of two different
      methylation regions: intergenic differential methylation region (IG-DMR) and MEG3
      DMR which control the expression of DLK1 and MEG3. Furthermore, Person
      correlation was used to make sure the association of methylation alteration of IG
      DMR and endothelium-derived factors. RESULTS: In our study, we found that DBP was
      significantly lower in preeclampsia offspring who born over 34 weeks compared
      with normal offspring (53.59 +/- 1.38 vs. 59.9 +/- 1.40 mmHg, P < 0.01), which
      leads to higher pulse pressure difference. Quantitative real-time PCR showed that
      imprinted gene DLK1 level significantly increased and MEG3 level decreased in
      HUVEC of preeclampsia group compared with control group, accompanying with lower
      expression of endothelial nitric oxide synthase and vascular endothelial growth
      factor (VEGF), higher expression of endothelin-1 (ET1), which are close related
      with vascular endothelial function. Meanwhile, ELISA assay of ET1, nitrite, VEGF
      were consistent with real-time results. Furthermore, abnormal expression of DLK1
      MEG3 expression was caused by hypermethylation status of IG-DMR, And methylation
      status of IG-DMR highly correlated with ET1 concentration and nitrate
      concentration, these might be one of the mechanisms for impaired endothelial
      function (coefficient = 0.5806, P = 0.0115; coefficient = -0.4883, P = 0.0398).
      CONCLUSION: Our results demonstrated that altered expression of imprinted genes
      DLK1 and MEG3 were caused by hypermethylation of IG-DMR in HUVEC of preeclampsia
      group, accompanied by lower secretion of nitrite, VEGF, and higher secretion of
      ET1. It might be one potential mechanism for higher risk of cardiovascular
      disease in preeclampsia offspring later in life.

PMID- 30234782
TI  - Carotid intima-media thickness, but not chronic kidney disease independently
      associates with noncardiac arterial vascular events in South Africa.
AB  - AIM: Although chronic kidney disease (CKD) as determined from estimated
      glomerular filtration rate (eGFR) is recommended for risk prediction by current
      hypertension guidelines, the equations to derive eGFR may not perform well in
      black Africans. We compared whether across the adult lifespan, eGFR or CKD are as
      closely associated with noncardiac arterial vascular events, as carotid intima
      media thickness (IMT), in Africa. METHODS: In 1152 black South Africans [480 with
      noncardiac arterial events (294 with critical lower limb ischemia, 186 with
      stroke) of which 37% were premature] and 672 age, sex and ethnicity-matched
      controls from a randomly selected community sample, we assessed relations between
      eGFR, CKD or carotid IMT (B-mode ultrasound) and arterial events. RESULTS: From
      20 years until old age, with or without adjustments, IMT was increased in those
      with as compared with without events (P < 0.01 at each decade of age). However,
      at any decade of age across the adult lifespan neither creatinine concentrations,
      nor eGFR were altered in those with arterial events (P > 0.28). Although IMT was
      strongly and independently associated with the odds of an event [odds ratio per 1
      SD (0.171 mm) effect = 2.19, confidence interval = 1.75-2.78, P < 0.0001],
      neither creatinine concentrations (P = 0.89), modification of diet in renal
      disease-derived (P = 0.07), nor Chronic Kidney Disease Epidemiology Collaboration
      derived [odds ratio per 1 SD (22.5 ml/min per 1.73 m) effect = 1.06, confidence
      interval = 0.89-1.27, P = 0.51] eGFR were independently associated with the odds
      of an event. Although many with premature events had an increased IMT (63%), few
      with either premature events (8%) or with events at an older age (21%) had CKD
      and CKD had a poor performance (0.539 +/- 0.011) and low sensitivity (16%) for
      event detection. CONCLUSION: In black South Africans, despite carotid IMT
      strongly associating with noncardiac arterial vascular events (stroke and
      critical lower limb ischaemia) consistently across the adult lifespan, few with
      events have CKD and CKD fails to associate with events.

PMID- 30234783
TI  - Agreement between 24-h dietary recalls and 24-h urine collections for estimating
      sodium intake in China, Japan, UK, USA: the International Study of Macro- and
      Micro-nutrients and Blood Pressure.
AB  - OBJECTIVE: The present study aims to compare 24-h dietary recalls with 24-h urine
      collections for the estimation of sodium intake at both population and individual
      levels in China, Japan, the United Kingdom (UK), and the United States of America
      (USA), using data from the International Study of Macro- and Micro-nutrients and
      Blood Pressure (INTERMAP). METHODS: Mean differences between 24-h dietary recalls
      and 24-h urine collections were calculated for their agreement in estimating
      sodium intake at the population level; relative and absolute differences as well
      as misclassification of salt intake groups (salt intake <6, 6-8.9, 9-11.9, 12
      14.9, and >=15 g/day) were used to determine the agreement at the individual
      level. RESULTS: The mean differences (95% CI) between dietary recalls and urine
      collections for China, Japan, UK, and USA were -54.0 (-59.8, -48.3), 3.9 (0.6,
      7.2), 2.9 (-1.8, 7.6), and -3.5 (-5.8, -1.1) mmol/day, respectively. The
      proportions of individual relative differences beyond +/-40% were 34.3% for
      China, 16.9% for Japan, 24.2% for UK, and 21.3% for USA; the proportions of
      individual absolute differences greater than 51.3 mmol/day (3 g salt) were 58.6%
      for China, 32.8% for Japan, 25.4% for UK, and 31.9% for USA. The rate for
      misclassification of salt intake groups at individual level for China, Japan, UK,
      and USA were 71.4, 60.9, 58.7, and 60.0%, respectively. CONCLUSION: The 24-h
      dietary recalls demonstrate greater agreement with the 24-h urine collections in
      estimating population sodium intake for Japan, UK, and USA, compared with China.
      The 24-h dietary recall has poor performance in assessing individual sodium
      intake in these four countries.

PMID- 30234784
TI  - Determinants of pulse wave velocity trajectories from youth to young adulthood:
      the Georgia Stress and Heart Study.
AB  - OBJECTIVE: Increased arterial stiffness measured by pulse wave velocity (PWV) has
      been shown to be an important parameter of cardiovascular risk. Longitudinal
      development of PWV from youth to early adulthood and its possible
      sociodemographic, anthropometric, hemodynamic and behavioral moderators will be
      illustrated. METHODS: Individual growth curves of carotid-distal PWV across age
      were created for 559 African American and European American men and women with a
      maximum of five assessments over an average of 7-year follow-up (mean age at
      participants' first assessment, 22.3 +/- 3.4). RESULTS: African Americans and men
      had significantly higher PWV than did European Americans and women (Ps < 0.01),
      respectively. A three-way interaction (P < 0.001) between age, sex and ethnicity
      was observed with African American men displaying a larger rate of increase in
      PWV with age than the other three ethnic and sex groups. The ethnicity and sex
      effects on PWV persisted when controlling for other moderators. Waist
      circumference was the strongest anthropometric predictor but its effect on PWV
      was only significant in women. Mean arterial pressure was the strongest
      hemodynamic predictor, marital status of parents was the strongest socioeconomic
      predictor and marijuana use was the strongest behavioral predictor of PWV. The
      best-fitting full model explained in total 59.4% of the between-subject variance
      in PWV with ethnicity, sex and age explaining 25.6%. CONCLUSION: We observed
      significant ethnic and sex differences in longitudinal trajectories of PWV in
      youth and young adults. In addition, individual differences in PWV growth can
      largely be explained by mean arterial pressure, waist, marital status of parents
      and marijuana use.

PMID- 30234785
TI  - The utility of long-term blood pressure variability for cardiovascular risk
      prediction in primary care.
AB  - OBJECTIVES: Blood pressure (BP) is a long-established risk factor for
      cardiovascular disease (CVD). SBP is used in all widely used cardiovascular risk
      scores for clinical decision-making. Recently, within-person BP variability has
      been shown to be a major predictor of CVD. We investigated whether cardiovascular
      risk scores could be improved by incorporating BP variability with standard risk
      factors. METHODS: We used cohort data on patients aged 40-74 on 1 January 2005,
      from English general practices contributing to the Clinical Practice Research
      Datalink, a research database derived from electronic health records. Data were
      linked to hospital episodes and mortality data. SBP variability independent of
      the mean was calculated across up to six clinic visits. We divided data
      geographically into derivation and validation data sets. In the derivation data
      set, we developed a reference model, incorporating risk factors used in previous
      scores and an index model, incorporating the same factors and BP variability. We
      calculated model validation statistics in the validation data set including
      calibration ratio and c-statistic. RESULTS: In the derivation data set, BP
      variability was associated with CVD, independently of other risk factors (P =
      0.005). However, in the validation data set, both models had similar c-statistic
      (0.7415 and 0.7419, respectively), R (31.8 and 32.0, respectively) and
      calibration ratio (0.938 and 0.940, respectively). CONCLUSION: The association of
      BP variability with CVD is statistically significant in a large data set but does
      not substantially improve the performance of a cardiovascular risk score.

PMID- 30234786
TI  - Different prognostic associations of beta-blockers and diuretics in heart failure
      with preserved ejection fraction with versus without high blood pressure.
AB  - OBJECTIVE: No agents have been proven to improve survival in heart failure with
      preserved ejection fraction (HFpEF), but the phenotypic diversity of HFpEF
      suggests it may be possible to identify specific HFpEF phenotypes that will
      benefit from certain treatments. This study compared the risk factors for and
      prognostic impacts of treatments on in-hospital mortality between HFpEF patients
      with (+) and without (-) high blood pressure (HBP). METHODS: Data on 2238
      consecutive HFpEF patients were extracted from Tokyo CCU Network data registry
      and analysed. HFpEF was defined as an ejection fraction greater than or equal to
      50%; HBP was defined as elevated systolic blood pressure (>140 mmHg) at
      admission. Potential risk factors for in-hospital mortality were selected by
      univariate analyses and those with P < 0.10 were used in multivariate Cox
      regression analysis with forward selection (likelihood ratio) to identify
      significant factors. RESULTS: In-hospital mortality was significantly lower for
      HFpEF + HBP than HFpEF - HBP patients (log-rank, P < 0.001). Independent risk
      factors for in-hospital mortality in HFpEF + HBP patients were older age (hazard
      ratio 1.069) and in-hospital treatment without beta-blockers (hazard ratio
      7.946), whereas older age (hazard ratio 1.035), higher C-reactive protein (hazard
      ratio 1.047), higher B-type natriuretic peptide (hazard ratio 1.000) and in
      hospital treatment without diuretics (hazard ratio 4.201) were identified as
      independent risk factors in HFpEF - HBP patients. CONCLUSION: There were
      significant differences in prognostic factors, including beta-blocker and
      diuretic treatments, for in-hospital mortality between HFpEF patients with and
      without HBP. These findings suggest possible individualized therapies for
      patients with HFpEF.

PMID- 30234787
TI  - Kinetics of Torque Teno Virus-DNA Plasma Load Predict Rejection in Lung
      Transplant Recipients.
AB  - BACKGROUND: Lung transplantation is the only therapeutic option in end stage lung
      diseases, however, survival after transplantation is limited by acute and chronic
      rejection or infectious events being results of inappropriate immunosuppression.
      Torque Teno Viruses (TTV) are ubiquitous DNA viruses in humans but not found to
      be causative for any disease. However, some reports suggest that TTV-DNA levels
      reflect the grade of immunosuppression with higher levels being found in more
      immunosuppressed individuals. METHODS: We investigated the TTV-DNA levels in 34
      lung transplant recipients within their first year following transplantation by
      quantitative real-time PCR. Clinical data were extracted from charts. RESULTS: In
      accordance with previous results TTV-DNA levels increase after lung
      transplantation reaching a steady state after 3 months. TTV-DNA levels were not
      correlated with immunosuppressive trough levels and a selective increase was not
      observed with other DNA viruses. In steady state TTV-DNA levels were
      significantly higher in patients with infectious complications compared to the
      group of patients without. Additionally, TTV-DNA levels decreased significantly
      prior to biopsy-proven rejection. Sensitivity of a 10-fold decrease in TTV-DNA
      levels for a subsequent rejection episode was 0.74 with a specificity of 0.99.
      CONCLUSIONS: In summary TTV-DNA might be used as an additional tool to monitor
      immunosuppression in lung transplant recipients. Higher TTV-DNA levels reflect
      more intense immunosuppression, whereas the TTV-DNA kinetic (ie, decrease of TTV
      DNA levels) indicate rejection.

PMID- 30234789
TI  - VCA Deceased Donors in the United States.
AB  - BACKGROUND: Vascularized composite allograft (VCA) transplants include diverse
      organ types and are made possible primarily by deceased donors. METHODS: We used
      Organ Procurement and Transplantation Network (OPTN) data to characterize VCA
      deceased donors (n=66 of 70) in the United States 1998-2017 and compare their
      characteristics with those of kidney donors in 2017. RESULTS: Through December
      31, 2017, 20 transplant programs performed 72 deceased donor VCA transplants,
      with organs donated by 70 donors, including 30 upper limb (17 unilateral and 13
      bilateral) and 11 face donors. Other donors donated both upper limbs and face
      (n=2), uterus (n=4), abdominal wall (n=19), larynx (n=2), penis (n=1), and scalp
      (n=1). About a third of VCA donors were female, and the majority (86.4%) were
      white. Almost half (45.5%) were between 18 and 34 years old. Smaller proportions
      were under 18 (19.7%), 35-44 (15.2%), 45-54 (13.6%), and over 55 years old
      (6.1%). Median body mass index for all VCA donors was 24.9 and varied widely,
      especially for upper limb and face donors. There was considerable variation in
      Kidney Donor Profile Index among VCA donors (median: 27.5; interquartile range:
      11-59). Donor causes of death included head trauma (39.4%),
      cerebrovascular/stroke (25.8%), and anoxia (31.8%). VCA donors also donated solid
      organs that were transplanted, including 87.1% of kidneys, 93.9% of livers, 40.2%
      of lungs, and 56.1% of hearts. CONCLUSIONS: VCA donors are a demographically and
      clinically diverse group. Understanding this diversity and future trends in VCA
      donor characteristics is critical in supporting this life-changing field of
      transplantation.

PMID- 30234788
TI  - Potentiating Renal Regeneration using Mesenchymal Stem Cells.
AB  - BACKGROUND: The potential of a Mesenchymal Stem Cell (MSC) therapy to accelerate
      the repair of ischemically damaged human kidneys during 24 hours of warm
      perfusion was evaluated. The hypothesis was that by administering MSC directly to
      the renal tissue, there would be an improved opportunity for cellular repair
      mediated by intrarenal paracrine effects. METHODS: Studies were performed using
      the Exsanguinous Metabolic Support (EMS) tissue-engineering platform. Five pairs
      of human kidney allografts from donation after cardiac death (DCD) donors were
      studied. One human kidney was EMS perfused for 24 hours (control), while its
      paired kidney was EMS perfused with MSC (1*10). The kidneys were evaluated for
      DNA synthesis, cytokine/chemokine synthesis, cytoskeletal regeneration and
      mitosis. RESULTS: Treatment with MSC resulted in reduced inflammatory cytokines
      synthesized by the kidneys. MSC treatment led to a significant increase in the
      synthesis of ATP and growth factors resulting in normalization of metabolism and
      the cytoskeleton. Toluidine Blue staining of MSC treated kidneys demonstrated a
      significant increase in the number of renal cells undergoing mitosis (26%)
      compared to EMS perfusion alone. CONCLUSIONS: To our knowledge, our work is the
      first to have demonstrated actual renal regeneration while ischemically damaged
      human kidneys are perfused ex vivo for 24 hours. The observed regeneration
      entails: increased synthesis of ATP, a reduced inflammatory response, increased
      synthesis of growth factors, normalization of the cytoskeleton and mitosis. The
      ability to regenerate renal tissue ex vivo sufficiently to result in immediate
      function could revolutionize transplantation by solving the chronic organ
      shortage.

PMID- 30234790
TI  - Antituberculosis Drug-Induced Liver Injury in Children: Incidence and Risk
      Factors During the Two-Month Intensive Phase of Therapy.
AB  - BACKGROUND: As one of the most frequent and serious adverse reactions during
      tuberculosis treatment, antituberculosis drug-induced liver injury (ATLI) in
      children has been studied insufficiently compared with adults. We aimed to
      determine the incidence and risk factors of ATLI in children during the first two
      months of TB-therapy. METHODS: A total of 41 children with tuberculosis and
      treated with first-line antituberculosis drugs were prospectively followed-up for
      the development of ATLI.Liver function tests were performed at baseline and after
      two weeks of therapy. Subsequent tests were conducted at 4, 6 and eight weeks if
      the initial 2-week measurement was abnormal, or if symptoms of hepatotoxicity
      were reported. RESULTS: ATLI was detected in 11 (27%) patients within 14 to 42
      days from the start of therapy, with most of them (54%) occurred after two weeks.
      TB treatment was stopped immediately in 6 out of 11 patients who developed ATLI,
      and no recurrent hepatotoxicity after drug reintroductions in these patients.
      Univariate analysis showed that ATLI was significantly associated with TB
      meningitis (p<0.01), hypoalbuminemia (p<0.05) and hepatotoxic co-medications
      (p<0.01). Age, gender, nutritional status, HIV status, and baseline liver
      function abnormalities were not associated with ATLI. Multivariate analysis
      identified hypoalbuminemia and hepatotoxic co-medications (both p<0.1) tend to be
      independently associated with ATLI. CONCLUSIONS: Children with hypoalbuminemia
      and use of hepatotoxic co-medications are suggested to be monitored closely for
      the development of ATLI.

PMID- 30234791
TI  - The Effectiveness of Ledipasvir/Sofosbuvir in Youth with Genotype 4 Hepatitis C
      Virus; A Single Egyptian Center Study.
AB  - BACKGROUND: Licensure of ledipasvir/sofosbuvir for chronic hepatitis C virus
      (HCV) infection in adolescents, was based upon clinical trials on patients mainly
      with genotype-1. We aimed to evaluate the effectiveness and short-term safety of
      this newly approved antiviral in adolescents with HCV genotype-4. METHOD: This
      was a study of 51 HCV-infected adolescents, who received the adult dose of
      ledipasvir/sofosbuvir, once daily for 12 weeks, and were followed-up for 12 weeks
      post-treatment. Laboratory tests, quantitation of HCV RNA, HCV genotyping, IL
      28rs gene polymorphism, and transient elastography were performed at baseline.
      Follow up visits were done for blood testing and adverse events recording.
      RESULTS: The mean age was 14.7+1.5 years (11-17.5), with a male to female ratio
      of 1.7:1. All patients were genotype 4a, and 76.5% had the CC IL-28 gene
      polymorphism. About 50% gave a history of HCV-infected mother, and 31% were
      treatment-experienced. Liver stiffness was F0 in 72.5%, F0-F1 in 13.7%, and F1-F2
      in 13.7%. Adverse events were mainly, abdominal pain in 72.5%, headache in 64.7%,
      and diarrhea in 53% of patients; these were was mild.. A reversible increase in
      creatinine level with a concomitant decline in eGFR was observed in the first
      month of treatment. By the end of week 12, a significant decline in liver enzymes
      was observed. All patients achieved an early, end of treatment, and a sustained
      virologic response. CONCLUSION: Adolescent patients with genotype 4 chronic HCV
      infection, achieved a good response rate with good on-treatment tolerability for
      ledipasvir/sofosbuvir therapy.

PMID- 30234792
TI  - HIV Viremia During Pregnancy and Neurodevelopment of HIV-Exposed Uninfected
      Children in the Context of Universal Antiretroviral Therapy and Breastfeeding: A
      Prospective Study.
AB  - BACKGROUND: Elevated HIV viral load (HIV-VL) in pregnancy has been linked to
      increased risk of mortality, immunological abnormalities, infectious morbidity
      and restricted growth among HIV-exposed uninfected (HEU) children, but little is
      known about effects on child development. METHODS: HIV-infected women initiating
      lifelong ART (tenofovir+emtricitabine+efavirenz) antenatally were followed from
      first antenatal visit through delivery and with their breastfed infants
      postpartum. Cognitive, motor and expressive language development (Bayley Scales
      of Infant and Toddler Development, BSID-III; delay defined as score <85) were
      assessed on a subset of HEU infants. HIV-VL was measured at ART initiation, in
      third trimester and around delivery. Cumulative viraemia in pregnancy was
      expressed as log10 VL copies x year/mL (viraemia copy-years, VCY). Relationships
      between VCY and development were examined after adjusting for socio-economic,
      behavioural and psychosocial confounders. RESULTS: Women (median pre-ART log10 VL
      4.1, CD4 349 cells/mm) commonly reported adverse social circumstances (44%
      informal housing, 63% unemployed, 29% risky drinking). Among 214 infants (median
      age 13 months; 53% male; 13% born <37 weeks' gestation), viraemia predicted lower
      motor and expressive language, but not cognitive, scores in crude and adjusted
      analysis [per log10 VCY increase, abeta (95%CI): motor, -2.94 (-5.77; -0.11);
      language, -3.71 (-6.73; -0.69) and cognitive-2.19 (-5.02; 0.65)]. Increasing VCY
      also predicted higher relative odds of motor delay [adjusted odds ratio, aOR 3.32
      (95% CI 1.36; 8.14)] and expressive language delay [aOR 2.79 (95% CI 1.57; 4.94),
      but not cognitive delay [aOR 1.68 (0.84; 3.34)]. CONCLUSION: Cumulative maternal
      HIV viraemia in pregnancy may have adverse implications for HEU child
      development.

PMID- 30234794
TI  - ANATOMICAL CHANGES BETWEEN ARGUS II RETINAL PROSTHESIS AND INNER RETINAL LAYERS
      DETECTED BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN FIRST YEAR: A CASE
      REPORT.
AB  - PURPOSE: To report and describe the anatomical changes detected by spectral
      domain optical coherence tomography between an Argus II retinal prosthesis and
      the inner retinal layers during 1-year follow-up. METHODS AND RESULTS: A patient
      presented with epiretinal fibrosis 12 months after implant of an Argus II
      epiretinal prosthesis. One month after uneventful surgery in March 2016, an
      evident hyporeflective space was detected between the epiretinal prosthesis and
      the inner retinal surface by spectral domain optical coherence tomography. An
      epiretinal hyperreflective band was noticed during follow-up and 1 year after
      surgery. Spectral domain optical coherence tomography showed close contact of the
      band with the array, which greatly increased the electrical threshold of
      stimulation for most of the electrodes. Some electrodes were no longer
      functioning. No changes in visual performance were detected. CONCLUSION: Argus II
      epiretinal prosthesis implant may be complicated by the formation of a
      hyperreflective epiretinal band, detectable by spectral domain optical coherence
      tomography. The band may alter prosthesis function; to date, the patient did not
      scored any decrease in visual function.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.

PMID- 30234793
TI  - Twenty-Nine Cases of Enterovirus-D68 Associated Acute Flaccid Myelitis in Europe
      2016; A Case Series and Epidemiologic Overview.
AB  - BACKGROUND: Enterovirus D68 (EV-D68) is a respiratory virus within the genus
      Enterovirus and the family of Picornaviridae. Genetically, it is closely related
      to rhinovirus that replicates in the respiratory tract and causes respiratory
      disease. Since 2014, EV-D68 has been associated with the neurologic syndrome of
      acute flaccid myelitis (AFM). METHODS: In October 2016, questionnaires were sent
      out to a European network including 66 virologists and clinicians, to develop an
      inventory of EV-D68 associated AFM cases in Europe. Clinical and virologic
      information of case patients was requested. In addition, epidemiologic
      information on EV-testing was collected for the period between March and October
      2016. RESULTS: Twenty-nine cases of EV-D68 associated AFM were identified, from
      12 different European countries. Five originated from France, 5 from Scotland and
      3 each from Sweden, Norway and Spain. Twenty-six were children (median age 3.8
      years), 3 were adults. EV-D68 was detected in respiratory materials (n=27), feces
      (n=8) and/or cerebrospinal fluid (n=2).Common clinical features were asymmetric
      flaccid limb weakness, cranial nerve deficits and bulbar symptoms. On magnetic
      resonance imaging, typical findings were hyperintensity of the central cord
      and/or brainstem; low motor amplitudes with normal conduction velocities were
      seen on electromyography. Full clinical recovery was rare (n=3), and 2 patients
      died.The epidemiologic data from 16 European laboratories showed that of all EV
      D68 positive samples, 99% was detected in a respiratory specimen. CONCLUSIONS:
      For 2016, 29 EV-D68 related AFM cases were identified in mostly Western Europe.
      This is likely an underestimation, since case identification is dependent on
      awareness among clinicians, adequate viral diagnostics on respiratory samples,
      and the capability of laboratories to type EVs.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.

PMID- 30234795
TI  - Risk Factor Reversal in Studies of Infectious Disease: Making Counterintuitive
      Results Intuitive Again.
AB  - A previously published study reported the seemingly paradoxical finding that MSM
      status was strongly protective and recent sexual abstinence strongly deleterious
      in relation to mortality prognosis. We explain why these results are entirely
      logical, and that the counterintuitive direction of the effects derives from the
      comparison group implied by the study design.

PMID- 30234796
TI  - Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates in Yaounde,
      Cameroon From 2009 to 2014.
AB  - We investigated the antimicrobial resistance in gonococci 2009 to 2014 in
      Yaounde, Cameroon, and recommend revisions of the Cameroonian treatment
      guideline. We observed a high resistance to ciprofloxacin (17.6%) but no
      ceftriaxone resistance. Ceftriaxone should replace ciprofloxacin as the
      recommended first-line treatment for urethral/vaginal discharge. Enhanced
      resistance surveillance in Africa is essential.

PMID- 30234797
TI  - Changes in the Use of Lumbar Arthrodesis Procedures within Accountable Care
      Organizations.
AB  - STUDY DESIGN: Retrospective review of Medicare claims data (2009-2014).
      OBJECTIVE: To evaluate changes in the use of lumbar fusion procedures following
      the formation of Accountable Care Organizations (ACOs). SUMMARY OF BACKGROUND
      DATA: Within surgical care afforded by ACOs, savings are thought to be realized
      by improved care coordination as well as reductions in the use of preference
      sensitive procedures such as lumbar fusion. METHODS: We queried fee-for-service
      claims for patients enrolled in Medicare Part A and B, identifying patients who
      received lumbar spine fusion, discectomy or decompression procedures. We
      performed a difference-in-differences analysis comparing the use of lumbar fusion
      in ACOs and non-ACOs in the period before (2009-2011) and after (2012-2014) ACO
      formation. Propensity score adjustment was used to address differences in case
      mix. Multivariable logistic regression was used to compare the likelihood of
      receiving a lumbar fusion in ACOs and non-ACOs in the period before and after ACO
      formation. RESULTS: Within organizations that would form ACOs, the raw rate of
      lumbar fusion increased from 50% (n = 2,183) in 2009-2011 to 54% (n = 2,283) in
      2012-2014. Among non-ACOs, the use of fusion increased from 52% (n = 110,160) to
      59% (n = 109,917). Adjusted difference in differences in the use of lumbar fusion
      between ACOs and non-ACOs was -2.6 percentage points (p = 0.13). When limited to
      patients with spinal stenosis, ACOs significantly reduced the use of fusion (-5.8
      percentage points; p = 0.03). CONCLUSION: Our results indicate that ACOs may
      effectively curtail the use of lumbar fusion procedures, particularly among
      patients with spinal stenosis. As these interventions are often associated with
      higher complications and need for reoperation, such practices might accrue
      additional healthcare savings for Medicare beyond those realized during the index
      surgical period. LEVEL OF EVIDENCE: 3.

PMID- 30234798
TI  - Surgical Outcomes for Drop Body Syndrome in Adult Spinal Deformity.
AB  - STUDY DESIGN: Multicenter retrospective case series of patients treated
      surgically for adult spinal deformity (ASD). OBJECTIVE: To compare clinical
      outcomes between propensity-score-matched ASD patients with or without drop body
      syndrome (DBS). SUMMARY OF BACKGROUND DATA: DBS is an extreme primary sagittal
      plane deformity often seen in Asian countries. Although the importance of
      sagittal alignment is widely recognized, surgical outcomes for deformities purely
      in the sagittal plane are poorly understood. METHODS: This study included 243
      consecutive patients (age 66 +/- 17 years; range 22-78) who were treated
      surgically for ASD and were followed at least 2 years (mean follow-up 3.7 +/- 2.3
      years). DBS was defined as a primary lumbar kyphosis with PI-LL>40 degrees , Cobb
      angle <30 degrees , and multifidus cross-sectional area <300 mm. DBS Patients
      were matched with non-DBS patients by propensity scores for age, gender, LIV
      level, and number of levels fused. Demographics, radiographic findings, and
      clinical outcomes were compared between DBS and non-DBS patients. RESULTS: Of 243
      patients with ASD, 34 had DBS (14%); 28 of these were propensity-matched with ASD
      patients without DBS. Baseline BMD, BMI, and frailty were similar in DBS and non
      DBS patients. Baseline sagittal alignment was worse in DBS than non-DBS patients
      (C7SVA 14 +/- 5 vs. 8 +/- 5 cm; PI - LL 60 +/- 14 vs. 36 +/- 20 degrees ), and
      SRS22 scores were also worse for DBS patients (2.5 +/- 0.6 vs. 2.9 +/- 0.8).
      Although DBS patients had more complications (20 DBS vs. 16 non-DBS), the
      clinical outcomes were similarly improved in both groups after surgery. At the 2
      year follow-up, the spinopelvic malalignment was worse in DBS than non-DBS
      patients (PI-LL 17 +/- 16 vs. 8 +/- 13 degrees , p < .05). CONCLUSIONS: DBS
      affected 14% of 234 ASD patients. Although DBS patients had inferior baseline
      SRS22 scores than non-DBS patients, ASD surgery resulted in similar clinical
      improvement in both groups. Future studies should examine the influence of
      lifestyle and genetics on clinical outcomes after surgery for DBS. LEVEL OF
      EVIDENCE: 3.

PMID- 30234799
TI  - Comparison of Postoperative Outcomes According to Compensatory Changes of the
      Thoracic Spine Among Patients with a T1 Slope More Than 40 degrees .
AB  - STUDY DESIGN: Retrospective study of postoperative outcomes of adult spinal
      deformity (ASD) surgery. OBJECTIVE: To clarify the differences in postoperative
      outcomes depending on the presence or absence of thoracic compensatory changes
      among patients with a T1 slope (TS)more than 40 degrees . SUMMARY OF BACKGROUND
      DATA: Loss correction after ASD surgery is more likely to occur when preoperative
      TS ismore than 40 degrees . When preoperative TS is more than 40 degrees , some
      cases involve compensatory changes in the thoracic spine and decreased thoracic
      kyphosis (TK); others involve increased TK without compensatory changes. METHODS:
      Seventy-nine patients with TSmore than 40 degrees  who underwent ASD surgery were
      enrolled and separated into compensated and non-compensatedgroups (group C:TK <40
      degrees ;group NC: TK >=40 degrees ). Radiographic parameters obtained by whole
      spine standing X-ray, the Oswestry Disability Index (ODI), and Scoliosis Research
      Society-22 (SRS-22) questionnaire were assessed. RESULTS: There were 41 patients
      in group C and 38 patients in group NC.Preoperative significant differences in TS
      did not disappear after surgery (preoperative TS: group C and group NC = 46
      degrees  and 55 degrees , P < 0.001; just after surgery: group C and group NC =
      27 degrees  and 40 degrees , P < 0.001; 2 years later: group C and group NC = 34
      degrees  and 47 degrees , P < 0.001).There were no significant differences in ODI
      and all domains of the SRS-22 before surgery. However, 2 years after the surgery,
      ODI (38%), pain (3.5), self-image (3.0), and total (3.2) values of the SRS-22 for
      group NC were significantly worse than those(28%, 4.0, 3.4, and 3.5,
      respectively) for group C (P < 0.05). CONCLUSION: Changes in the thoracic spine
      (TS and TK more than 40 degrees ) result in poor postoperative outcomes.
      Extending the upper instrumented vertebra (UIV) to the upper thoracic spine must
      be considered.Even when TS ismore than 40 degrees , TK less than 40 degrees  and
      UIV set to the lower thoracic level result ingood postoperative outcomes. LEVEL
      OF EVIDENCE: 3.

PMID- 30234800
TI  - Safety and Efficacy of Revision Minimally Invasive Lumbar Decompression in the
      Ambulatory Setting.
AB  - STUDY DESIGN: Retrospective Analysis. OBJECTIVE: To investigate differences in
      perioperative outcomes between patients undergoing revision minimally invasive
      lumbar spine decompression (MIS LD) in the ambulatory and hospital-based surgical
      settings. SUMMARY OF BACKGROUND DATA: Revision LD has been associated with an
      increased risk of complications compared to primary LD. Furthermore, ambulatory
      primary LD has been demonstrated to be a safe and viable option in appropriately
      selected patients. However, there is a paucity of information comparing hospital
      based versus ambulatory outcomes in revision LD. METHODS: A prospectively
      maintained surgical registry of patients undergoing revision MIS lumbar
      laminectomy and/or discectomy for degenerative pathology from 2013-2017 was
      retrospectively reviewed. Propensity score matching was performed to adjust for
      measured confounding variables, including patient age, comorbidity burden as
      measured by Charlson Comorbidity Index, and preoperative diagnosis. Differences
      in operative variables, complication rates, pain scores, narcotics consumption,
      and reoperation rates were assessed using Pearson's chi-squared analysis
      (categorical) and Student's t-test (continuous). RESULTS: Seventy patients were
      included, of 35 underwent revision MIS LD at a hospital-based center (HBC), and
      35 underwent surgery at an ambulatory surgical center (ASC). HBC and ASC patients
      demonstrated similar postoperative visual analog scale pain scores and hourly
      narcotics consumption during surgical stay (p < 0.001). ASC patients exhibited a
      significantly shorter length of stay as compared to hospital-based patients (2.7
      vs 11.6 hours, p < 0.001). CONCLUSION: Patients undergoing revision MIS LD in an
      ASC demonstrated similar perioperative outcomes as compared to patients
      undergoing revision MIS LD in a hospital-based center. These results suggest
      revision MIS LD can be performed safe and effectively in the ambulatory setting
      in an appropriately selected surgical population. Further study of patient
      outcomes following spine surgery performed outside of the traditional hospital
      setting is crucial as the delivery of care in the ambulatory setting continues to
      grow in popularity. LEVEL OF EVIDENCE: 3.

PMID- 30234801
TI  - Predictive Factors of Post-operative Dysphagia in Single-level Anterior Cervical
      Discectomy and Fusion (ACDF).
AB  - STUDY DESIGN: Retrospective review of prospectively collected data OBJECTIVE.: To
      investigate if zero profile devices offer an advantage over traditional
      plate/cage constructs for dysphagia rates in single level ACDF. SUMMARY OF
      BACKGROUND DATA: Dysphagia rates following ACDF have been reported to be as high
      as 83%, most cases are self-limiting, but chronic dysphagia can continue in up to
      35% of patients. Zero profile devices were developed to limit dysphagia, and
      other plate specific complications, however the literature is currently divided
      regarding their efficacy. METHODS: Dysphagia was assessed by SWAL-QOL scores pre
      operatively, at 6 weeks and 12 weeks. PROMs including VAS and NDI were collected
      pre operatively, at 6 weeks and at 6 months. Univariate and multivariate
      regression analysis was conducted with SWAL-QOL score as the dependent variable.
      RESULTS: 64 patients were included, 41 received a zero profile device, and 23
      received plate/cage construct. Both groups were similar regarding patient
      demographics, except operative time, with the zero-profile group having a shorter
      procedure time than the cage-plate group (44.88 +/- 6.54 vs 54.43 +/- 14.71
      minutes, p = 0.001). At all timepoints dysphagia rates were similar between the
      groups. Regression analysis confirmed pre-operative SWAL-QOL and operative time
      were the only significant variables. PROMs were also similar between groups at
      all time points, except VAS neck at 6 months, which was lower in the plate-graft
      group (1.05 +/- 1.48 vs 3.43 +/- 3.21, p = 0.007). CONCLUSIONS: Operative time
      and pre-operative SWAL-QOL scores are predictive of dysphagia in single level
      ACDF. Zero profile devices had a significantly shorter operative time, and may
      provide a benefit in dysphagia rates in this regard. LEVEL OF EVIDENCE: 3.

PMID- 30234802
TI  - Replication Study for the Association of GWAS-associated Loci with Adolescent
      Idiopathic Scoliosis Susceptibility and Curve Progression in a Chinese
      Population.
AB  - STUDY DESIGN: A genetic association (replication) study. OBJECTIVE: To replicate
      and further evaluation the association seven GWAS identified SNPs in Chinese
      girls with adolescent idiopathic scoliosis (AIS) with disease onset, curve types,
      and progression. SUMMARY OF BACKGROUND DATA: AIS is the most common paediatric
      spinal deformity with a strong genetic predisposition. Recent GWAS identified 10
      new disease predisposition loci for AIS. METHODS: 319 female AIS patients with
      Cobb angle >= 10 and 201 healthy controls were studied for association with
      disease onset. Seven GWAS identified SNPs (rs11190870 in LBX1, rs12946942 in
      SOX9/KCNJ2, rs13398147 in PAX3/EPH4, rs241215 in AJAP1, rs3904778 in BNC2,
      rs6570507 in GPR126 and rs678741 in LBX1-AS1) were analysed. In subgroup
      analysis, AIS patients were subdivided by curve types and disease progression to
      examine for genotype association. RESULTS: We replicated the association with
      disease onset in 4 common SNPs rs11190870, rs3904778, rs6570507 and rs678741. In
      addition, rs1190870 and rs678741 remained significantly associated in the right
      thoracic curves only subgroup. However, no significant difference was observed
      with both clinical curve progression or Cobb angle. CONCLUSION: This study
      replicated the associations of 4 GWAS-associated SNPs with occurrence of AIS in
      our Chinese population. However, none of these SNPs was associated with curve
      severity and progression. The results suggest that curve progression may be
      determined by environmental (non-genetic) factor but further study with larger
      sample size is required to address this issue. LEVEL OF EVIDENCE: 4.

PMID- 30234803
TI  - Psychometric Properties Study of the Oswestry Disability Index in a Spanish
      Population with Previous Lumbar Disc Surgery: Homogeneity and Validity.
AB  - STUDY DESIGN: Evaluation of the psychometric properties of a questionnaire.
      OBJECTIVE: To assess the psychometric properties of the Spanish version of the
      Oswestry Disability Index (ODI) in a Spanish population with previous lumbar disc
      surgery. SUMMARY OF BACKGROUND DATA: ODI is frequently used for measuring
      disability in spinal disorders. In 1995, ODI was translated and transculturally
      adapted into the Spanish context; its content and apparent validity, internal
      consistency and test-retest reliability were demonstrated for a Spanish
      population with lumbar pain. However, this score has not been tested in terms of
      discriminative capacity (floor and ceiling effects) and construct validity.
      METHODS: 275 patients who had previously undergone surgical treatment for disc
      lumbar herniation completed the ODI, Short-Form 36 (SF36), EuroQol-5D (EQ5D) and
      Numerical Rating Scale for Back Pain (NRS-BP). Internal consistency, floor and
      ceiling effects and construct validity (convergent, divergent and "known-groups"
      validities) were assessed. RESULTS: Spanish ODI showed a very good internal
      consistency: Cronbach-alpha coefficient for ODI score was 0.928; Cronbach-alpha
      coefficient, if the item was deleted, did not increase by more than 0.1 for each
      item; and Item-total correlations ranged from strong to very strong. There was
      floor effect for both ODI score and for all individual items. There was no
      ceiling effect. Spanish ODI showed very good construct validity because 88% (7/8)
      of the hypotheses about convergent, divergent and "known-groups" validities were
      supported. Concerning convergent validity, ODI was strongly correlated with the
      NRS-BP (0.717;p < 0.001), SF36-Utility (rho = -0.786;p < 0.001), Physical
      Component Summary score SF36 (rho = -0.787;p < 0.001), Mental Component Summary
      score SF36 (rho = -0.605;p < 0.001), EQ5D-Utility (rho = -0.833;p < 0.001) and
      some EQ5D physical components. CONCLUSIONS: Spanish ODI showed good psychometric
      properties (internal consistency and construct validity), similar to others
      validation studies. Spanish ODI is a valid instrument for the measurement of
      disability in Spanish patients with previous lumbar disc surgery, specifically in
      patients with moderate/intense disability. LEVEL OF EVIDENCE: 4.

PMID- 30234804
TI  - Biomechanical Comparison of C1 Lateral Mass - C2 Short Pedicle Screw - C3 Lateral
      Mass Screw-Rod Construct Versus Goel-Harms Fixation For Atlantoaxial Instability.
AB  - STUDY DESIGN: A biomechanical in vitro study using human cadaveric spines.
      OBJECTIVE: To compare atlantoaxial stability and stiffness of a C1 lateral mass -
      C2 short pedicle - C3 lateral mass screw-rod construct versus C1 lateral mass -
      C2 pedicle screw-rod construct. SUMMARY OF BACKGROUND DATA: The C1 lateral mass -
      C2 pedicle screw-rod construct provides excellent atlantoaxial fixation but C2
      pedicle screw placement is associated with risk of vertebral artery injury. The
      use of shorter C2 pedicle screws may mitigate the risk of vascular injury but may
      result in reduced C1-C2 stabilization. Extending C1 lateral mass - C2 short
      pedicle screw-rod construct with C3 lateral mass screws may mitigate the risk of
      vascular injury without compromising C1-C2 fixation. METHODS: Seven cervical
      spines were tested with internal control experimental design in the following
      sequence: intact state, and following creation of type II odontoid fracture, the
      specimen was instrumented with C1 lateral mass - C2 pedicle screw fixation
      (C2PED), C1 lateral mass - C2 short pedicle screw fixation (C2SPED) and C1
      lateral mass - C2 short pedicle - C3 lateral mass screw fixation (C2SPED-C3LM).
      For each condition, the angular stiffness and range of motion with 1.5 Nm load in
      flexion/extension (FE), lateral bending (LB) and right/left axial rotation
      (RAR/LAR) were quantified. RESULTS: Instrumented conditions demonstrated
      significantly lower C1-C2 angular range of motion (ROM) and greater stiffness
      than the intact state. Compared to C2PED, C2SPED-C3LM demonstrated significantly
      lower C1-C2 ROM during FE and LB, significantly greater C1-C2 stiffness in
      flexion and right/left LB, similar C1-C2 ROM and stiffness in RAR/LAR and similar
      stiffness in extension. C2SPED-C3LM demonstrated significantly greater
      atlantoaxial stabilization in the sagittal and coronal planes compared to C2PED
      construct. CONCLUSIONS: Compared to C2PED, C2SPED-C3LM may be a suitable
      alternative surgical strategy for atlantoaxial instability that provides superior
      atlantoaxial fixation. LEVEL OF EVIDENCE: N/A.

PMID- 30234805
TI  - Patients cannot Reliably Distinguish the Iliac Crest Bone Graft Donor Site From
      the Contralateral Side after Lumbar Spine Fusion: A Patient-Blinded Randomized
      Controlled Trial.
AB  - STUDY DESIGN: A multicenter, randomized, intra-patient controlled trial.
      OBJECTIVE: This study investigated whether lumbar fusion patients blinded to the
      harvest site 1) can identify the iliac crest used for bone harvesting and 2)
      whether this iliac crest is more painful than the contralateral side. SUMMARY OF
      BACKGROUND DATA: Spinal fusion with iliac crest autograft is a frequently
      performed surgical procedure. A widely reported disadvantage of the harvesting
      procedure is potential donor site morbidity. This has driven the development of
      many bone graft substitutes. However, more recently the incidence and severity of
      donor site pain is debated, especially in lumbar fusion surgery. METHODS: Ninety
      two non-traumatic adult patients underwent a posterolateral (thoraco)lumbar
      fusion. Iliac crest bone graft was harvested unilaterally through the primary
      midline incision. At 6 weeks, 3 months, 6 months and 1 year follow-up, patients
      were asked to identify the donor site and to rate pain in their back, left iliac
      crest and right iliac crest on a Visual Analogue Scale. RESULTS: Ninety patients,
      44 males and 46 females with a mean age of 54 years, were analyzed. The
      left/right distribution of the iliac crest donor site was 50/50 and 89% of the
      patients underwent a lumbar fusion below L3. Only 24% patients identified the
      harvest site correctly. Moreover, the VAS pain scores for the donor site and
      contralateral iliac crest did not differ and were at each timepoint lower than
      the scores for back pain. CONCLUSIONS: This study showed that, during the first
      year after lumbar fusion surgery via a single midline incision approach, patients
      could not reliably identify the iliac crest used for bone graft harvesting and
      this iliac crest was not more painful than the untouched contralateral iliac
      crest. Therefore, donor site pain should not be the main reason to use bone graft
      alternatives for lumbar spinal fusion. LEVEL OF EVIDENCE: 2.

PMID- 30234806
TI  - Risk of Surgical Site Infection and Mortality Following Lumbar Fusion Surgery in
      patients with Chronic Steroid Usage and Chronic MRSA infection.
AB  - STUDY DESIGN: Retrospective database analysis among Medicare beneficiaries
      OBJECTIVE.: To determine the effect of chronic steroid use and chronic
      Methicillin Resistant Staphylococcus Aureus (MRSA) infection on rates of surgical
      site infection and mortality in patients 65 years of age and older who were
      treated with lumbar spine fusion. SUMMARY OF BACKGROUND DATA: Systemic
      immunosuppresssion and infection focus elsewhere in the body are considered risk
      for surgical site infection (SSI). Chronic steroid use and previous MRSA
      infection have been associated with increased risk of SSI in some surgical
      procedures, but their impact on the risk of infection and mortality after lumbar
      fusion surgery has not been studied in detail. METHODS: The PearlDiver insurance
      based database (2005-2012) was queried to identify 360,005patients over 65 years
      of age who had undergone lumbar spine fusion. Of these patients, those who had
      been taking oral glucocorticoids chronically and those with a history of chronic
      MRSA infection were identified. The rates of surgical site infection (SSI) and
      mortality in these two cohorts were compared to an age- and risk-factor matched
      control cohort and odds ratio was calculated. RESULTS: Chronic oral steroid use
      was associated with significantly increased risk of 1 year mortality (OR = 2.06,
      95%CI 1.13-3.78 p = 0.018) and significantly increased risk of SSI at 90 days (OR
      = 1.74, 95%CI 1.33-1.92 p < 0.001) and 1 year (OR = 1.88, (95%CI 1.41-2.01 p <
      0.001). Chronic MRSA infection was associated with significantly increased risk
      of SSI at 90 days (OR = 6.99, 995%CI 5.61-9.91 p < 0.001) and 1 year (OR = 24.0,
      95%CI 22.20-28.46 p < 0.001) but did not significantly impact mortality.
      CONCLUSIONS: Patients over 65 years of age who are on chronic oral steroids or
      have a history of chronic MRSA infection are at significantly increased risk of
      surgical site infection following lumbar spine fusion. LEVEL OF EVIDENCE: 3.

PMID- 30234807
TI  - Cross-cultural Adaptation and Validation of the Simplified-Chinese version of
      Neck Bournemouth Questionnaire for Patients in Mainland China.
AB  - STUDY DESIGN: Prospective. OBJECTIVE: To develop and assess the internal
      reliability and structure validity of a simplified Chinese version of the Neck
      Bournemouth Questionnaire (SC-NBQ) for evaluation of patients with nonspecific
      neck pain (NP) in mainland China. SUMMARY OF BACKGROUND DATA: The NBQ has been
      cross-culturally translated into several languages with good internal consistency
      and construct validity to evaluate low back pain and NP. However, the NBQ has not
      translated or validated for Chinese speaking patients. METHODS: The SC-NBQ was
      developed by standard cross-translation procedures, and completed by 106 patients
      with nonspecific NP, along with other self-reported questionnaires including the
      Neck Disability Index (NDI), Hospital Anxiety and Depression Scale (HADS),
      Functional Rating Index (FRI), and 36-Item Short Form Health Survey (SF-36). The
      internal consistency, test-retest reliability, and construct validity of the SC
      NBQ were determined. RESULTS: The NBQ was successfully translated into Chinese.
      All patients completed the SC-NBQ twice, and the other instruments. Score
      distribution demonstrated that there was no floor or ceiling effects of the SC
      NBQ. Cronbach alpha coefficient (alpha = 0.89) and intra-class correlation
      coefficient (ICC = 0.97) showed good internal consistency and test-retest
      reliability. A good construct validity was shown by strong correlation with HADS
      (r = 0.75), NDI (r = 0.82), FRI (r = 0.90) and SF-36 physical functioning (r =
      0.75) and bodily pain (r = 0.75) subscales. CONCLUSION: The SC-NBQ demonstrated
      good internal consistency, test-retest reliability, and construct validity, and
      may be used for the evaluation of NP in Chinese speaking patients. LEVEL OF
      EVIDENCE: 2.

PMID- 30234808
TI  - Increased Osteoblastic Activity Suppressed Proliferation of Multiple Myeloma
      Plasma Cells.
AB  - STUDY DESIGN: In vitro experimental study. OBJECTIVES: To investigate the impact
      of increased osteoblastic activity on the proliferation and survival of MM plasma
      cells in vitro SUMMARY OF BACKGROUND DATA.: Multiple myeloma (MM) is one of
      representative hematologic malignancies that cause skeletal-related events (SREs)
      and dysregulation of bone remodeling is known as a key pathomechanism of disease
      progression and skeletal-related events. However, decreased proliferation of MM
      at fracture sites is frequently noted in clinical situations regardless of
      systemic disease activity METHODS.: Co-culture under various conditions was used
      to investigate effects of increased osteoblastic activity on survival and
      proliferation of MM plasma cells. MM plasma cells were cultured in culture media
      (control) and co-cultured with human mesenchymal stem cells (hMSCs, group I),
      osteoblasts (OBs) induced from hMSCs (group II) or bone morphogenic protein-2
      (BMP-2, group III). Proliferation measured as ERK and Ig G expressionand
      apoptosis measured as FACS with annexin V method, caspase-3 and stat-3 expression
      were assessed forcultured MM plasma cells, along with expression of sclerostin.
      RESULTS: After 72 hrs of co-culture, group II and III showed decreased ERK
      expression compared with controls. Lower Ig G expression was also noted for
      groups II and III compared with controls. Group I did not show significantly
      decreased Ig G and ERK expression compared with controls. Expressions of caspase
      3 in groups II and III were higher than controls. Co-culture with hMSCs showed
      decreased caspase-3 expression compared to control. FACS with annexin V showed
      higher apoptosis in groups II and III. Sclerostin expression was also decreased
      in osteoblastic conditions compared to the control and hMSCs co-culture
      condition. CONCLUSIONS: Collectively, our data suggest that increased
      osteoblastic conditions may provide not only prevention of SREs but also anti
      tumor effects on MM cells in the bone marrow environment. LEVEL OF EVIDENCE: N/A.

PMID- 30234809
TI  - Evaluating the Quality, Content and Readability of Online Resources for Failed
      Back Spinal Surgery.
AB  - STUDY DESIGN: An Internet-based assessment of websites using recognized score
      systems. OBJECTIVE: To assess the quality, content, and readability of online
      information for failed back spinal surgery (FBSS). SUMMARY OF BACKGROUND DATA: A
      significant amount of patients still suffer from chronic or recurrent back pain
      with or without radicular symptoms after spinal surgery. More and more patients
      use the Internet to find health-related information. Low-quality or inaccurate
      information may not only misleading patients but also have a negative impact on
      the trust between patients and physicians. METHODS: The terms "chronic pain after
      spinal surgery", "chronic pain after back surgery", "failed back surgery
      syndrome", "post spinal surgery syndrome" and "post laminectomy syndrome" were
      entered into three search engines (Google, Yahoo!, and Bing). The first 25
      websites from each search were reviewed. The quality, content, and readability of
      each website were evaluated using DISCERN score, FBSS- specific content score,
      and the JAMA benchmark criteria, the first two score systems were assessed by
      three reviewers independently. The Flesch-Kincaid grade level (FKGL) was used to
      assess the readability. Each website with or without the Health on the Net Code
      (HONcode) was also recorded. RESULTS: Seventy-two websites were analyzed in our
      study. The average DISCERN score for all websites was 35.26 +/- 11.45, indicating
      the quality of the websites was poor. The DISCERN score of physician websites was
      31.25 +/- 9.08, lower than that of media (36.50 +/- 0.71, p = 0.017) and
      commercial websites (42.55 +/- 10.93, p = 0.045). The mean FBSS-specific content
      score was 9.58 +/- 3.90 out of maximum 25. We failed to find any difference of
      FBSS-specific content score among different type of website. Websites with
      HONcode certification were associated with higher DISCERN score, FBSS- specific
      content score, and JAMA benchmark criteria score than non-certified websites. The
      mean FKGL was 12.19 +/- 2.20, and none of the websites' FKGL was lower than the
      six grade level. CONCLUSIONS: The quality and content of available online
      information for FBSS were poor. The readability of online information in our
      results showed a significantly higher reading level than the sixth-grade level
      recommended by the AMA and NIH. LEVEL OF EVIDENCE: 4.

PMID- 30234810
TI  - Epidemiological State, Predictors of Early Mortality, and Predictive Models for
      Traumatic Spinal Cord Injury: A Multicenter Nationwide Cohort Study.
AB  - STUDY DESIGN: Multi-center, retrospective cohort study. OBJECTIVE: To determine
      the epidemiology, identify predictors of early mortality, and develop predictive
      models for traumatic spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA:
      Despite improved initial care and management strategies, traumatic SCI remains a
      devastating event. Knowledge of the epidemiological state and predictive factors
      for mortality is important for developing strategies and counseling; however,
      they have not been adequately investigated, and predictive modeling regarding
      outcomes remains an underused modality for patients with traumatic SCI. METHODS:
      Using a nationwide trauma registry-the Japan Trauma Data Bank-we identified adult
      (>=18 years) patients with SCI between 2004 and 2015. The endpoint was in
      hospital mortality. Characteristics of each patient were described. Multivariate
      logistic regression analyses were performed to identify factors significantly
      associated with in-hospital mortality and develop a predictive model. RESULTS: In
      total, 236,698 patients were registered in the database. Of the 215,835 adult
      patients, 8,069 (3.7%) had SCI. The majority had SCI at the cervical level with
      falls at ground level being the primary etiology. Over the study period, median
      age, the proportion of cervical SCI, and the etiology of falls at ground level
      increased. The mortality rate was 5.6%. The following eight factors, age, sex,
      Glasgow Coma Scale on arrival (GCS), hypotension on arrival, bradycardia on
      arrival, severe head injury, Injury Severity Score (ISS), and neurological
      severity of SCI, were independently associated with mortality. A predictive model
      consisting of these variables predicted mortality with area under the receiver
      operating characteristic curve of 0.88 (95% CI, 0.86-0.90). CONCLUSIONS: Over the
      12-year period, patient characteristics, etiology, and post-SCI outcomes
      significantly changed. We identified 8 prognostic factors of early mortality. A
      predictive model including these factors showed excellent performance and may
      improve treatment strategies, healthcare resource allocation, and counseling.
      LEVEL OF EVIDENCE: 3.

PMID- 30234812
TI  - Heterotopic ossification and spinal cord injury.

PMID- 30234811
TI  - The Rates of Lumbar Spinal Stenosis Surgery in Norwegian Public Hospitals; A
      Threefold Increase from 1999 to 2013.
AB  - STUDY DESIGN: Retrospective administrative database study. OBJECTIVE: To assess
      temporal and regional trends, and length of hospital stay, in lumbar spinal
      stenosis (LSS) surgery in Norwegian public hospitals from 1999 to 2013. SUMMARY
      OF BACKGROUND DATA: Studies from several countries have reported increasing rates
      of LSS surgery over the last decades. No such data have been presented from
      Norway. METHODS: A database consisting of discharges from all Norwegian public
      hospitals was established. Inclusion criteria were discharges including a
      surgical procedure of lumbar spinal decompression and/or fusion in combination
      with an ICD-10 diagnosis of Spinal Stenosis (M48.0) or Other Spondylosis with
      Radiculopathy (M47.2), and a patient age of 18 years or older. Discharges with
      diagnoses indicating deformity, i.e. spondylolisthesis or scoliosis were not
      included. RESULTS: During the 15-year period, 19 543 discharges were identified.
      The annual rate of decompressions increased from 10.7 to 36.2 and fusions
      increased from 2.5 to 4.4 per 100 000 people of the general Norwegian population.
      The proportion of fusion surgery decreased from 19.3% to 10.9%. Among individuals
      older than 65 years, the annual rate of surgery per 10000, including both
      decompressions and fusions, more than quadrupled from 40.2 to 170.3. The regional
      variation was modest, differing with a factor of 1.4 between the region with the
      highest and the lowest surgical rates. The mean length of hospital stay decreased
      from 11.0 (SD 8.0) days in 1999 to 5.0 (4.6) days in 2013, but patients who
      received fusion surgery stayed on average 3.6 days longer than those who received
      decompression only. CONCLUSIONS: The rate of LSS surgery more than tripled in
      Norway from 1999 to 2013. The mean length of hospital stay was reduced from 11 to
      5 days. LEVEL OF EVIDENCE: 4.

PMID- 30234813
TI  - Practice Variation Among Surgeons Treating Lumbar Spinal Stenosis in a Single
      Institution.
AB  - STUDY DESIGN: Retrospective study OBJECTIVE.: To examine practice variation in
      the treatment of lumbar spinal stenosis and identify targets for reducing
      variation. SUMMARY OF BACKGROUND DATA: Lumbar spinal stenosis is a degenerative
      condition susceptible to practice variation. Reducing variation aims to improve
      quality, increase safety, and lower costs. Establishing differences in surgeons'
      practices from a single institution can help identify personalized variation.
      METHODS: We identified adult patients first diagnosed with lumbar spinal stenosis
      between 2003 and 2015 in three hospitals of the same institution with ICD-9
      codes.We extracted number of office visits, imaging procedures, injections,
      EMG's, and surgery within the first year after diagnosis; physical therapy within
      the first 3 months after diagnosis. Multivariable logistic regression was used to
      identify factors associated with surgery. The coefficient of variation (CV) was
      calculated to compare the variation in practice. RESULTS: The 10,858 patients we
      included had an average of 2.5 visits (+/-1.9), 1.5imaging procedures (+/-2.0),
      0.03EMG's (+/-0.22), and 0.16injections (+/-0.53); 36% had at least 1 surgical
      procedure and 32% had physical therapy as part of their care. The CV was smallest
      for number of visits (19%) and largest for EMG (140%).Male sex (Odds Ratio [OR]:
      1.23, p < 0.001), seeing an additional surgeon (OR: 2.82, p < 0.001), and having
      an additional spine diagnosis (OR: 3.71, p < 0.001) were independently associated
      with surgery. Visiting an orthopedic clinic (OR: 0.46, p < 0.001) was
      independently associated with less surgical interventionthan visiting a
      neurosurgical clinic. CONCLUSIONS: There is widespread variation in the entire
      spectrum of diagnosis and therapy for lumbar spinal stenosis among surgeons in
      the same institution. Male gender, seeing an additional surgeon, having an
      additional spine diagnosis, and visiting a neurosurgery clinic were independently
      associated with increased surgical intervention. The main target we identified
      for decreasing variability was the use of diagnostic EMG. LEVEL OF EVIDENCE: 3.

PMID- 30234814
TI  - Preoperative age and prognostic nutritional index are useful factors for
      evaluating postoperative delirium among patients with adult spinal deformity.
AB  - STUDY DESIGN: A retrospective study of postoperative delirium following adult
      spinal deformity (ASD) surgery. OBJECTIVE: To identify the risk factors of post
      ASD surgery delirium, including nutritional state before surgery. SUMMARY OF
      BACKGROUND DATA: Recently, malnutrition was reported as one of the risk factors
      of delirium. The prognostic nutritional index (PNI) and controlling nutritional
      status index (CONUT) scores are simple methods of nutritional evaluation.
      However, there are no reports that verify that delirium is related to the PNI and
      CONUT score in patients who have undergone ASD surgery. METHODS: A consecutive
      319 patients who underwent ASD surgery were divided into a delirium group (group
      D) or non-delirium group (group ND). Preoperative risk factors, including PNI,
      were assessed. RESULTS: Group D consisted of 30 patients and Group ND consisted
      of 289 patients. There was significant difference in age (group D:group ND =
      73:62, P = 0.000), serum albumin (4.2:4.3, P = 0.028), operative time (422:395
      min, P = 0.029), PNI score (49:52, P = 0.011), and CONUT score (1.7:1.1, P =
      0.046). Using multiple logistic regression analysis, we found significant risk
      factors for delirium to be age (P = 0.006, odds ratio[OR] = 1.11, 95% confidence
      interval[CI] = 1.03-1.19) and PNI (P = 0.003, OR = 0.87, 95% CI = 0.79-0.96). A
      receiver operating characteristic curve showed that the cut-off value of PNI and
      age for delirium were 49.7 and 68.5 years, respectively. CONCLUSION: The risk
      factors of postoperative delirium following ASD surgery were PNI <49.7 and age
      >68.5 years. Patients who undergo ASD surgery beyond these preoperative cut-off
      values should be cautioned about delirium and be required to provide adequate
      informed consent. LEVEL OF EVIDENCE: 3.

PMID- 30234815
TI  - Improvement in Work Ability, Psychological Distress and Pain Sites in Relation to
      Low Back Pain Prognosis: A Longitudinal Observational Study in Primary Care.
AB  - STUDY DESIGN: Prospective observational study pooled from two clinical cohorts.
      OBJECTIVE: To investigate the longitudinal relation between multisite pain,
      psychological distress and work ability with disability, pain and quality of
      life. SUMMARY OF BACKGROUND DATA: Knowledge of prognostic factors is essential
      for better management of patients with low back pain (LBP). All domains of the
      biopsychosocial model has shown prognostic value; however, clinical studies
      rarely incorporates all domains when studying treatment outcome for LBP patients.
      METHODS: 165 Patients with non-specific LBP seeking primary care physiotherapy
      were included. Mixed-effects models were used to estimate longitudinal relations
      between the exposure variables and concurrent measures of outcomes at baseline
      and 3 months. Logistic regression was used to estimate odds ratios for minimal
      important difference in outcome. RESULTS: Higher work ability was associated with
      less disability -2.6 (95% CI: -3.3, -2.0), less pain: -0.4 (95% CI: -0.5, -0.3),
      and higher quality of life 0.03 (95% CI: 0.02, 0.04). Increased psychological
      distress and number of pain sites were associated with higher disability: 10.9
      (95% CI: 7.7, 14.1) and 1.9 (95% CI: 0.9, 2.8), higher pain: 1.9 (95% CI: 1.3,
      2.5) and 0.4 (95% CI: 0.2, 0.5), and lower quality of life: -0.1 (95% CI: -0.2, 
      0.1) and -0.02 (95% CI: -0.03, -0.01), respectively. Improvement in work ability
      showed consistent associations with successful outcome for disability (OR: 4.8,
      95% CI: 1.3, 18.1), pain (OR: 3.6, 95% CI: 1.1, 12.1) and quality of life (OR:
      4.5, 95% CI: 1.4, 15.1) at 3 months. Reduced psychological distress was
      associated with improvement in pain only (OR 4.0, 95% CI: 1.3, 12.3). CONCLUSION:
      More pain sites, higher psychological distress or lower work ability showed
      higher disability, more pain, and lower quality of life in patients with low back
      pain. Only improvement in work ability was consistently related to successful
      outcomes. LEVEL OF EVIDENCE: 2.

PMID- 30234816
TI  - Pedicle Screw Placement Using Augmented Reality Surgical Navigation with
      Intraoperative 3D Imaging: A First In-Human Prospective Cohort Study.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVE: The aim of this study
      was to evaluate the accuracy of pedicle screw placement using augmented reality
      surgical navigation in a clinical trial. SUMMARY OF BACKGROUND DATA: Recent
      cadaveric studies have shown improved accuracy for pedicle screw placement in the
      thoracic spine using augmented reality surgical navigation with intraoperative 3D
      imaging, without the need for peri-procedural X-ray. In this clinical study, we
      used the same system to place pedicle screws in the thoracic and lumbosacral
      spine of 20 patients. METHODS: The study was performed in a hybrid operating room
      with an integrated augmented reality surgical navigation system encompassing a
      surgical table, a motorized flat detector C-arm with intraoperative 2D/3D
      capabilities, integrated optical cameras for augmented reality navigation, and
      noninvasive patient motion tracking. Three independent reviewers assessed screw
      placement accuracy using the Gertzbein grading on 3D scans obtained prior to
      wound closure. In addition, the navigation time per screw placement was measured.
      RESULTS: One orthopedic spinal surgeon placed 253 lumbosacral and thoracic
      pedicle screws on 20 consenting patients scheduled for spinal fixation surgery.
      An overall accuracy of 94.1% of primarily thoracic pedicle screws was achieved.
      No screws were deemed severely misplaced (Gertzbein grade 3). Fifteen (5.9%)
      screws had 2-4 mm breach (Gertzbein grade 2), occurring in scoliosis patients
      only. Thirteen of those fifteen screws were larger than the pedicle in which they
      were placed. Two medial breaches were observed and thirteen were lateral.
      Thirteen of the grade 2 breaches were in the thoracic spine. The average screw
      placement time was 5.2 +/- 4.1 min. During the study, no device-related adverse
      event occurred. CONCLUSION: Augmented reality surgical navigation can be
      clinically used to place thoracic and lumbosacral pedicle screws with high
      accuracy and with acceptable navigation time. Consequently, the risk for revision
      surgery and complications could be minimized. LEVEL OF EVIDENCE: 3.

PMID- 30234817
TI  - Changes in the Sagittal Cranio-Cervical Posture Following a 12-Week Intervention
      Using a Simple Spinal Traction Device.
AB  - STUDY DESIGN: Non-controlled clinical trial OBJECTIVE.: To assess the efficacy of
      a simple home spinal traction device on sagittal cranio-cervical posture and
      related symptoms. SUMMARY OF BACKGROUND DATA: Forward head protraction (FHP) and
      cranio-cervical malalignment were shown to be consequential in the development
      adverse musculoskeletal radiographic findings and symptoms in that region.
      METHODS: Participants (n = 13, 18 - 36-year-old) were drawn from a mildly
      symptomatic population, all presented with cranio-cervical malalignment and
      considerable FHP. Participants used a simple home spinal traction device for 12
      weeks, 10 minutes/day. Sagittal cervical radiographs and the SF36 health survey
      were obtained pre/post intervention and guideline compliance was recorded.
      Radiographic evaluation included typical measurements of sagittal cranio-cervical
      alignment and FHP (e.g. atlas plane line, vertical axis line, sagittal cranial
      angle, absolute rotation angle). Standard paired samples t-tests, CHI Squared and
      Effect Size analyses were used to assess pre- and post-intervention changes.
      RESULTS: Each of the key radiographic variables recorded significant moderate to
      very large positive changes as a result of the intervention. Similarly, CHI
      squared analyses indicated that saggital cervical spine configuration tended to
      become more lordotic (P = 0.007), with four participants shifting from a kyphotic
      to a lordotic presentation. SF36 health survey data demonstrated mostly
      significant positive changes throughout all tested domains, and moderate positive
      changes were recorded across all radiographic cranio-cervical mesured paramenters
      (e.g. decreased FHP, increased cervical lordosis and cranial extention).
      Participants indicated high level of protocol compliance. CONCLUSIONS: This study
      has demonstrated that the unsupervised daily use of a simple home spinal traction
      device (Thoracic Pillow(r)) proved effective in bringing positive plastic changes
      to the sagittal cranio-cervical alignment and reduction in symptoms in the tested
      population during a short intervention period. LEVEL OF EVIDENCE: 3.

PMID- 30234818
TI  - Comparing the Diagnostic Accuracies of F-18 FDG PET and MRI for the Detection of
      Spondylodiscitis: A Meta-Analysis.
AB  - STUDY DESIGN: A meta-analysis. OBJECTIVE: The aim of this study was to compare
      the diagnostic accuracies of F-18 fluorodeoxyglucose (F-18 FDG) positron emission
      tomography (PET) and magnetic resonance imaging (MRI) for the detection of
      spondylodiscitis through a meta-analysis. SUMMARY OF BACKGROUND DATA: There is no
      meta-analysis study that compares the diagnostic accuracies of F-18 FDG PET and
      MRI for the detection of spondylodiscitis. METHODS: The MEDLINE and EMBASE
      databases were searched from the earliest available date of indexing to January
      10, 2018 for studies comparing the diagnostic performance F-18 FDG PET with that
      of MRI for the detection of spondylodiscitis. We determined the sensitivities and
      specificities across studies, calculated the positive and negative likelihood
      ratios (LR+ and LR-), and constructed the summary receiver operating
      characteristic curves. RESULTS: In the seven studies (212 patients) selected, the
      pooled sensitivity and specificity of F-18 FDG PET were 0.95 (95% confidence
      interval [CI]: 0.87-0.98) and 0.88 (95% CI: 0.73-0.95), respectively. The LR
      syntheses showed an overall LR+ of 7.6 (95% CI: 3.4-17.2) and LR- of 0.05 (95%
      CI: 0.02-0.14). The pooled diagnostic odds ratio (DOR) was 141 (95% CI: 44-444).
      The pooled sensitivity and specificity of MRI were 0.85 (95% CI: 0.65-0.95) and
      0.66 (95% CI: 0.48-0.80), respectively. The LR syntheses showed an overall LR+ of
      2.5 (95% CI: 1.5-4.2) and LR- of 0.22 (95% CI: 0.08-0.60). The pooled DOR was 11
      (95% CI: 3-42). In the meta-regression analysis, no variable was identified as
      the source of the study heterogeneity. CONCLUSIONS: The current meta-analysis
      shows that F-18 FDG PET has better diagnostic accuracy than MRI for the detection
      of spondylodiscitis. Further large multicenter studies would be necessary to
      substantiate the diagnostic accuracies of F-18 FDG PET and MRI for
      spondylodiscitis. LEVEL OF EVIDENCE: 2.

PMID- 30234819
TI  - 30-Day Mortality Following Surgery for Spinal Epidural Abscess: Incidence, Risk
      Factors, Predictive Algorithm, and Associated Complications.
AB  - STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To determine incidence
      and timing of mortality following surgery for spinal epidural abscess (SEA),
      identify risk factors for mortality, and identify complications associated with
      mortality. SUMMARY OF BACKGROUND DATA: SEA is a serious condition with
      potentially devastating sequelae. There is a paucity of literature characterizing
      mortality following surgery for SEA. METHODS: The National Surgical Quality
      Improvement Program (NSQIP) database was used. Patients with a diagnosis of SEA
      were included. A Cox proportional hazards model identified independent risk
      factors for 30-day mortality. A predictive model for mortality was created.
      Multivariate models identified postoperative complications associated with
      mortality. RESULTS: There were 1094 patients included, with 40 cases of mortality
      (3.7%), the majority of which occurred within 2 weeks postoperatively (70%).
      Independent risk factors for 30-day mortality were age>60 years (Hazard Ratio
      [HR]: 2.147, p = 0.027), diabetes (HR: 2.242, p = 0.015), respiratory
      comorbidities (HR: 2.416, p = 0.037), renal comorbidities (HR: 2.556, p = 0.022),
      disseminated cancer (HR: 5.219, p = 0.001), and preoperative thrombocytopenia
      (HR: 3.276, p = 0.001). A predictive algorithm predicts a 0.3% mortality for zero
      risk factors up to 37.5% for 4 or more risk factors. A ROC area under curve (AUC)
      was 0.761, signifying a fair predictor (95% CI: 0.683-0.839, p < 0.001). Cardiac
      arrest (adjusted odds ratio [aOR]: 72.240, 95% confidence interval [CI]: 27.8
      187.721, p < 0.001), septic shock (aOR: 15.382, 95% CI: 7.604-31.115, p < 0.001),
      and pneumonia (aOR: 2.84, 95% CI: 1.109-7.275, p = 0.03) were independently
      associated with mortality. CONCLUSIONS: The 30-day mortality rate following
      surgery for SEA was 3.7%. Of the mortalities that occurred within 30 days of
      surgery, the majority occurred within 2 weeks. Independent risk factors for
      mortality included older age, diabetes, hypertension, respiratory comorbidities,
      renal comorbidities, metastatic cancer, and thrombocytopenia. Risk for mortality
      ranged from 0.3% to 37.5% based on number of risk factors. Septic shock, cardiac
      arrest, and pneumonia were associated with mortality. LEVEL OF EVIDENCE: 3.

PMID- 30234820
TI  - Understanding the importance of diagnosis coding.

PMID- 30234821
TI  - Ensuring a return on your professional investment: The importance of a contract
      (part 1).

PMID- 30234823
TI  - Hypertriglyceridemia: A review of the evidence.

PMID- 30234822
TI  - Antidepressant use in breastfeeding women.

PMID- 30234824
TI  - Newest lipoglycopeptides for the management of acute bacterial skin and skin
      structure infections.

PMID- 30234825
TI  - Type 2 diabetes management: A practice guide for NPs.
AB  - Type 2 diabetes mellitus (T2DM) is an endocrine and metabolic disorder that
      requires ongoing medical management. If T2DM is not adequately assessed and
      managed, a wide spectrum of clinical manifestations and complications may occur.
      This article provides clinical guidance to NPs on the management of T2DM in
      primary care settings.

PMID- 30234826
TI  - Variable clinical presentations of babesiosis.
AB  - Human babesiosis continues to spread in multiple regions of the US. It is
      transmitted by Ixodes species ticks, as are Lyme disease and anaplasmosis. Its
      variable clinical presentations, together with serologic detection limitations,
      require that a high index of clinical suspicion be present for prompt diagnosis.
      This article discusses case examples showing the wide range of symptoms and
      presentations that are possible with babesiosis.

PMID- 30234828
TI  - Development of Silicone Hydrogel Antimicrobial Contact Lenses with Mel4 Peptide
      Coating.
AB  - SIGNIFICANCE: This study investigated the development of an antimicrobial coating
      on silicone hydrogel contact lenses that may have the capacity to reduce contact
      lens-related infection and inflammatory events. PURPOSE: The purpose of this
      study was to develop an effective antimicrobial coating for silicone hydrogel
      contact lenses by attachment of Mel4 peptide. METHODS: Lotrafilcon A, comfilcon
      A, somofilcon A, senofilcon A, and lotrafilcon B silicone hydrogel contact lenses
      were plasma coated with acrylic acid followed by Mel4 antimicrobial peptide
      immobilization by covalent coupling. Peptide immobilization was quantified by x
      ray electron spectroscopy. Contact lens diameter, base curve, center thickness,
      and lens surface wettability were measured by captive-bubble contact-angle
      technique. Antimicrobial activity of the lenses was determined against
      Pseudomonas aeruginosa and Staphylococcus aureus by viable plate count and also
      after soaking with artificial tears solution for 1 day. In vivo safety and
      biocompatibility were determined in an animal model for 1 week. RESULTS: Mel4
      peptide-coated silicone hydrogel contact lenses were associated with high
      antimicrobial inhibition (>2 log), except for lotrafilcon B and senofilcon A.
      Lotrafilcon B did not exhibit any activity, whereas senofilcon A showed 1.4- and
      0.7-log inhibition against P. aeruginosa and S. aureus, respectively. X-ray
      electron spectroscopy revealed significant increases in the lens surface-bound
      amide nitrogen in all contact lenses except for lotrafilcon B. All contact lens
      parameters remained unchanged except for the base curve and center thickness for
      senofilcon A. Mel4 immobilization was associated with a decrease in contact
      angle. Mel4-coated contact lens wear was not associated with any signs or
      symptoms of ocular irritation in a rabbit model study. Reduced antimicrobial
      activity was observed with all the lenses after soaking with artificial tears
      solution or rabbit wear. CONCLUSIONS: Mel4 antimicrobial coating may be an
      effective option for development of antimicrobial silicone hydrogel contact
      lenses.

PMID- 30234830
TI  - Shelf Life and Efficacy of Diagnostic Eye Drops.
AB  - SIGNIFICANCE: Pharmaceutical companies recommend discarding ophthalmic drugs 28
      days after opening. This study shows that diagnostic eye drops have a low risk of
      contamination over a 7-month period in a controlled clinical setup. The
      diagnostic efficiency seems to be preserved over this period. PURPOSE: The aim of
      this study was to evaluate the preservation period and the efficacy of ophthalmic
      preparations, such as 0.5% proparacaine hydrochloride, 1% tropicamide, 2.5%
      phenylephrine hydrochloride, and 1% cyclopentolate hydrochloride ophthalmic
      solution in a clinical and controlled setting. METHODS: Thirty-eight primary eye
      care students were recruited to participate in the study. They used 25 bottles of
      each diagnostic drop at the Clinique Universitaire de la Vision for a 7-month
      period. An analysis of the bacterial contamination was repeated 10 times using
      both an agar plate and a nutrient broth at 0, 2, 4, 6, and 8 weeks and at 3, 4,
      5, 6, and 7 months. The anesthetic, mydriatic, and cycloplegic effects were
      tested after 7 months of use and compared with nonopened ophthalmic bottles.
      RESULTS: During the 7-month period, 4971 drops of proparacaine, 3219 drops of
      tropicamide and phenylephrine, and 1896 drops of cyclopentolate were administered
      to the patients. A total of 226 contacts between bottles and biological tissues
      were reported. After the 10 inoculation sessions on the agar medium at the
      predetermined times, no bacterial and fungal contamination was noted. No patient
      reported eye infections for 2 weeks after the drop instillation. Moreover, there
      was no difference in the efficacy when compared with new drops. CONCLUSIONS:
      According to the results of the current study, diagnostic eye drops can be used
      with a low contamination risk beyond the recommendation date of 28 days up to 7
      months, with the same efficacy, in a controlled clinical context.

PMID- 30234829
TI  - iPhone-based Pupillometry: A Novel Approach for Assessing the Pupillary Light
      Reflex.
AB  - SIGNIFICANCE: The response of the pupil to a flash of light, the pupillary light
      reflex (PLR), is an important measure in optometry and in other fields of
      medicine that is typically evaluated by qualitative observation. Here we describe
      a simple, portable, iPhone-based pupillometer that quantifies the PLR in real
      time. PURPOSES: The purposes of this study were to describe a novel application
      that records the PLR and to compare its technical capabilities with a laboratory
      based infrared (IR) camera system. METHODS: Pupil sizes were measured from 15
      visually normal subjects (age, 19 to 65 years) using an IR camera system and the
      Sensitometer test. This test elicits pupillary constriction using the iPhone
      flash, records pupil size using the camera, and provides measurements in real
      time. Simultaneous recordings were obtained with the Sensitometer test and IR
      camera, and two measures were calculated: (1) dark-adapted steady-state pupil
      size and (2) minimum pupil size after the flash. The PLR was defined as the
      difference between these two measures. Pupil size was also recorded during the
      redilation phase after the flash. Bland-Altman analysis was used to assess the
      limits of agreement between the two methods. RESULTS: Statistically significant
      correlations between the IR and Sensitometer test measures were found for the PLR
      (r = 0.91, P < .001) and redilation size (r = 0.65, P = .03). Bland-Altman
      analysis indicated a mean PLR difference of 6% between these two methods. The PLR
      limit of agreement was 14%, indicating that 95% of subjects are expected to have
      IR and Sensitometer test measurements that differ by 14% or less. Bland-Altman
      analysis indicated a mean redilation size difference of 1% between the two
      methods; the limit of agreement was 5%. CONCLUSIONS: There is excellent agreement
      between pupil responses recorded using the Sensitometer test and IR camera. The
      Sensitometer test provides a highly promising approach for simple, portable,
      inexpensive pupillary measurements.

PMID- 30234831
TI  - Case Report: Importance of B-scan Ultrasonography for the Detection of Choroidal
      Melanoma.
AB  - SIGNIFICANCE: This case highlights the importance of using ultrasonography to
      evaluate an eye that has no clear view of the fundus. PURPOSE: Uveal melanoma
      stems from melanocytes found in the iris, ciliary body, and choroid, and it is
      the most common primary intraocular malignancy found in adults. The lesion is
      identified predominantly via fundus biomicroscopy and binocular indirect
      ophthalmoscopy. The authors present a unique case where visual evaluation of the
      fundus was not possible, and ultrasonography was used to assess the retina and
      choroid. CASE REPORT: A 38-year-old Hispanic man with prior ocular trauma
      presented with an eye that could not be clinically examined owing to complete
      pupil occlusion. The diagnosis of presumed uveal melanoma was made exclusively
      based on the outcome of ocular ultrasonography. Further histologic, antibody, and
      genetic testing was completed once the patient had undergone treatment of the
      affected eye and uveal melanoma was confirmed. CONCLUSIONS: In this rare
      instance, B-scan ultrasonography provided a finding that required the patient to
      undergo enucleation in an eye without visual potential. Genetic testing was then
      used to appropriately categorize the tumor as a class 1B melanoma, indicating
      that there is a risk of metastasis. Consequently, the patient is being monitored
      by a medical oncologist.

PMID- 30234832
TI  - Tear Lactoferrin and Features of Ocular Allergy in Different Severities of
      Meibomian Gland Dysfunction.
AB  - SIGNIFICANCE: Meibomian gland dysfunction, but not atrophy, was associated with
      lower tear lactoferrin concentration, greater dry eye, and allergic symptoms,
      indicating greater inflammation and discomfort in patients with lower meibomian
      gland expressibility. PURPOSE: Meibomian gland dysfunction can potentially damage
      adjacent palpebral structures, which may induce inflammation in accessory
      lacrimal glands and affect lactoferrin secretion. This study aimed to examine the
      relationships between the severity of meibomian gland dysfunction with tear
      lactoferrin, conjunctival cell morphology, and clinical features of ocular
      allergy. METHODS: Forty subjects were divided into two groups based on the
      severity of meibomian gland plugging and expressibility and secondarily based on
      its atrophy. Dry eye and allergy questionnaires; slit-lamp examination, including
      lid telangiectasia; and meibography were performed. Tear lactoferrin
      concentration was measured using TearScan 270 MicroAssay. Impression cytology was
      performed on the upper palpebral conjunctiva, and goblet cell density and
      epithelial squamous metaplasia were quantified. RESULTS: Twenty-two subjects with
      meibomian gland dysfunction were categorized into severely obstructed group
      (case), whereas 19 subjects had minimal/no obstruction (comparison). Lower
      lactoferrin (1.3 +/- 0.4 vs. 1.7 +/- 0.4 mg/mL, P = .007), greater dry eye (7 [1
      to 10] vs. 2 [0 to 5], P = .03), and allergy symptoms (9 [4 to 23] vs. 6 [0 to
      9], P = .05) were found in the cases compared with the comparisons. There were no
      differences in conjunctival cell morphology between groups. The plugging score
      was correlated with lactoferrin concentration (rho = -0.43, P = .006), dry eye
      (rho = 0.36, P = .02), and allergic symptoms (rho = 0.33, P = .04). Greater lid
      margin telangiectasia was associated with meibomian gland obstruction, but not
      atrophy. CONCLUSIONS: Meibomian gland activity/dysfunction, but not atrophy, may
      be associated with increased inflammation on the ocular surface. The inflammation
      may be sufficient to reduce tear lactoferrin production from damage to accessory
      lacrimal glands and/or meibomian gland and result in increased symptoms.

PMID- 30234833
TI  - Light Perception Vision Recovery After Treatment for Calcium Hydroxylapatite
      Cosmetic Filler-Induced Blindness.
AB  - A 51-year-old woman presented with no light perception vision of the right eye 12
      hours after another provider injected calcium hydroxylapatite into the glabella
      and dorsum of the nose. Exam and fluorescein angiography demonstrated optic nerve
      edema and choroidal hypoperfusion consistent with ischemia of the posterior
      ciliary circulation. The central retinal circulation appeared intact. One
      thousand two hundred units of retrobulbar hyaluronidase were injected urgently in
      several boluses. Oral prednisone and aspirin also were administered. Ocular
      massage was also initiated. One day later, visual acuity improved to light
      perception that remained stable at 3 months. Retrobulbar hyaluronidase injection,
      ocular massage, prednisone, and aspirin were correlated to recovery of light
      perception vision in this case of calcium hydroxylapatite filler embolization to
      the choroidal circulation. The mechanism for the recovery of some vision and the
      role of hyaluronidase and other medications remain uncertain. Further research in
      treatments for ophthalmic complications of facial fillers is warranted.

PMID- 30234834
TI  - Nasal and Lacrimal Sac Histopathology in Patients With Systemic Sarcoidosis
      Undergoing External Lacrimal Drainage Surgery.
AB  - PURPOSE: To review the histological findings in the lacrimal sac and nasal mucosa
      from patients with sarcoidosis undergoing external lacrimal drainage surgery.
      METHODS: All patients undergoing external dacryocystorhinostomy at Moorfields Eye
      Hospital with a known history of sarcoidosis had biopsies taken from the lacrimal
      sac and/or nasal mucosa during surgery. These patients were identified from
      databases at Moorfields Eye Hospital and the Institute of Ophthalmology, and
      their clinical notes were reviewed retrospectively for intraoperative findings
      with a view to identifying common trends. The histological findings of each
      biopsy were reviewed and classified as showing granulomas, nongranulomatous
      inflammation, or nonspecific fibrosis. RESULTS: Forty patients (29 females; 72%)
      were known to have systemic sarcoidosis prior to surgery, and they underwent 60
      external dacryocystorhinostomies. Paired histological samples were available from
      49/60 (82%) procedures, nasal biopsies alone in 3 dacryocystorhinostomies (5%),
      and solely lacrimal sac biopsies in 8 (13%). The main site of systemic
      sarcoidosis was pulmonary involvement (19 patients; 48%). Recorded operative
      findings included 9 large lacrimal sac mucoceles (29%), a "thick" (26%) or
      "inflamed" (9.7%) lacrimal sac mucosa, and "thick" (36%) or "friable" (32%) nasal
      mucosa. Noncaseating granulomas were identified in 34/57 (60%) sacs, and 45/52
      (87%) nasal tissues-this being in 31/49 (63%) of paired tissues. Chronic
      inflammation, without granulomas, was present in 20/57 (35%) lacrimal sacs but
      only in 5/52 (9.6%) of nasal biopsies. CONCLUSIONS: In patients with sarcoidosis
      undergoing external dacryocystorhinostomy, the characteristic histological
      feature-noncaseating granulomas-is present in most patients' lacrimal sac mucosa
      and in almost all of their nasal mucosae. The lacrimal sac and nasal mucosa often
      appears abnormal-thickened or friable-during surgery.

PMID- 30234835
TI  - Spontaneous Orbital Hemorrhage Related to the Extraocular Muscles.
AB  - PURPOSE: The authors present the largest series of patients to date of
      spontaneous hemorrhage in relation to extraocular muscles (EOMs). METHODS:
      Observational retrospective case series. Institutional review board approval was
      obtained. RESULTS: Eighteen patients with a mean age of 71 years presented with
      20 episodes of spontaneous orbital hemorrhage closely related to an EOM. Most
      patients woke with unilateral proptosis, pain, and diplopia. Vision was impaired
      in 25%. Imaging identified a characteristic well-circumscribed hematoma arising
      within the muscle sheath or intermuscular septum. Three episodes required
      surgical drainage. All patients had good recovery of vision. DISCUSSION: The
      authors describe a distinct clinical entity of idiopathic hemorrhages related to
      EOMs. No patient had an underlying vascular malformation or other lesion. The
      authors demonstrate that a proportion of these patients have vascular risk
      factors, namely, hypertension, hyperlipidemia, and antiplatelet use. This study
      suggests that inferior rectus is the most commonly affected EOM and shows that it
      is the muscle sheath or intermuscular septum of inferior rectus that is involved,
      rather than the muscle belly. Most patients can be managed conservatively with
      good visual outcomes. However, there were 3 exceptional cases that required
      surgical intervention. CONCLUSIONS: The findings that spontaneous orbital
      hemorrhages related to EOMs have certain predisposing factors, a characteristic
      radiological appearance, and a typically benign course will be helpful for
      clinicians in the management of this condition.

PMID- 30234836
TI  - Angular Vein Varix Congestion From Chronic Glasses Wear.
AB  - This is a case report of a symptomatic varicose angular vein exacerbated by
      chronic glasses wear. Compressing the vein in a recumbent position led to
      increased fullness of the medial canthal region and reproduced his symptoms.
      Obliteration by cauterization of the vein led to resolution of symptoms.

PMID- 30234837
TI  - Idiopathic Acquired Lacrimal Canalicular Obstruction.
AB  - PURPOSE: Acquired lacrimal canalicular obstruction has a variety of causes. In a
      small proportion of patients, no cause can be identified. This article describes
      a cohort of 27 patients with idiopathic acquired lacrimal canalicular obstruction
      encountered over a 28-year period. METHODS: The diagnostic database of the senior
      author was analyzed to identify all cases of idiopathic acquired lacrimal
      canalicular obstruction seen from 1990 to 2017. Demographic, clinical, and
      treatment details were analyzed. Patients with primary lacrimal punctal stenosis
      or closure were excluded from the analysis. RESULTS: The authors encountered 27
      patients with idiopathic acquired lacrimal canalicular obstruction (17 female,
      63%) aged 34 to 91 years (median: 65 years). The level of canalicular obstruction
      ranged from 1 to 10 mm from the punctum. Canalicular obstruction involved 1
      canaliculus in 4 patients, 2 in 14 (ipsilateral in all except one), 3 in 3, and
      all 4 in 6. One patient who presented with ipsilateral upper and lower
      canalicular obstructions developed contralateral upper and lower obstructions
      several years later, and another patient redeveloped obstructions after initial
      successful surgical repair. In all cases, there were no features on history or
      examination to suggest a cause for the canalicular obstruction. Follow up ranged
      from 1 to 260 months (mean: 39 months). Sixteen patients underwent surgical
      repair, 11 with a dacryocystorhinostomy and placement of a Lester Jones glass
      bypass tube, 2 had a canaliculo-dacryocystorhinostomy (anastomosis of the
      canaliculus to the nose), 2 had dacryocystorhinostomy and trephination of the
      canalicular obstruction with silicone intubation, and 1 had a
      dacryocystorhinostomy alone to try and improve drainage through a single patent
      canaliculus. CONCLUSION: Idiopathic acquired lacrimal canalicular obstruction is
      uncommon and occurs more frequently in older women. The condition may be slowly
      progressive and can affect one or more canaliculi at any level. Treatment is the
      same as for any other cause of acquired lacrimal canalicular obstruction.

PMID- 30234838
TI  - Age-Related Changes in the Clinical Phenotype of Compressive Optic Neuropathy in
      Thyroid Eye Disease.
AB  - PURPOSE: This study compares the age-related clinical features of thyroid eye
      disease-compressive optic neuropathy (TED-CON) to those with noncompressive
      disease (TED-NC). METHODS: A retrospective case series review of 165 orbits from
      121 patients with TED-CON were compared with an age- and gender-matched cohort of
      88 orbits from 44 patients with TED-NC with institutional review board approval.
      Clinical features including exophthalmos, dyschromatopsia, restricted ocular
      motility, visual acuity, and mean deviation on 24-2 Humphrey Visual Field were
      compared in 5 age groups. A previously validated formula, the Columbia TED-CON
      Diagnostic formula, used to mathematically predict the presence or absence of
      compressive optic neuropathy was applied, and the sensitivity and specificity of
      the formula was measured in each age group. RESULTS: Exophthalmos,
      dyschromatopsia, restricted ocular motility, and mean deviation on 24-2 Humphrey
      Visual Field vary significantly across age groups in patients with TED-CON.
      Conversely, only visual acuity and dyschromatopsia vary significantly across age
      groups in patients with TED-NC. There was a significant difference between the
      TED-CON and the TED-NC groups when comparing the 2 groups by decade. The Columbia
      TED-CON Diagnostic formula had high sensitivity and specificity (74-90%) in all
      age groups. CONCLUSIONS: This is the first study to date demonstrating the age
      related variability of clinical characteristics in a large series of patients
      with either TED-CON or TED-NC. The clinical phenotype of TED-CON varies
      significantly by decade when examining exophthalmos, dyschromatopsia, ocular
      motility restriction, and mean deviation on 24-2 Humphrey Visual Field. These
      clinical characteristics are also significantly different when compared with a
      population of patients with TED-NC.

PMID- 30234839
TI  - The Role of Inferior Turbinate Fracture in the Management of Congenital
      Nasolacrimal Duct Obstruction.
AB  - PURPOSE: To evaluate the effect of inferior turbinate fracture in the treatment
      of congenital nasolacrimal obstruction combined with first attempt probing in
      children younger than 36 months. METHODS: This prospective case-control study was
      conducted on 230 eyes from 176 children aged 12 to 36 months with congenital
      nasolacrimal duct obstruction. All patients underwent simple probing under
      general anesthesia. Inferior turbinate fracture was performed in case group
      combined with first probing. Patients were followed up 1, 3, and 6 months after
      surgery. RESULTS: Total success rate was 91.2% for patients with turbinate
      fracture and 86.4% for patients without turbinate fracture. The difference
      between success rates was not statistically significant (p = 0.269). The authors
      did not find significant difference between cases and controls in age subgroups.
      Success rate in combined case and control groups in patients younger than 24
      months (success rate: 91.7%) was significantly higher than those older than 24
      months (success rate: 71.9%; p = 0.001). In univariate logistic regression
      analysis, age >=24 months showed a negative association with the success rate
      (odds ratio = 0.232; 95% confidence interval: 0.91-0.59; p = 0.002). Other
      factors like sex, bilaterality of nasolacrimal duct obstruction, method of
      probing were not significantly associated with response to treatment.
      CONCLUSIONS: Inferior turbinate fracture does not improve the outcomes of simple
      probing and is not recommended during the first attempt in treatment of
      congenital nasolacrimal duct obstruction. Late probing (after 24 months of age)
      may have a higher failure rate, and increased age is the important factor that
      predicts failure in probing simple congenital nasolacrimal duct obstruction.

PMID- 30234840
TI  - The Effects of Smoking on Spinal Cord Stimulation Outcomes: Another Reason to
      Quit.

PMID- 30234841
TI  - Transverse Approach to the Erector Spinae Block.

PMID- 30234842
TI  - Ultrasound-Guided Axillary Tunnel Block Revisited: In Answer.

PMID- 30234843
TI  - Combined Retroclavicular Approach for Shoulder Surgery: A New Description
      Technique of 3-in-1 Combined Block.

PMID- 30234844
TI  - Understanding ESP and Fascial Plane Blocks: A Challenge to Omniscience.

PMID- 30234845
TI  - Reply to Dr Chin et al.

PMID- 30234847
TI  - Microanatomical Nerve Architecture of 6 Mammalian Species: is Trans-species
      Translational Anatomic Extrapolation Valid?: Erratum.

PMID- 30234846
TI  - #WomeninPainMedicine: We Are Here.

PMID- 30234848
TI  - Oculomotor, Vestibular, and Reaction Time Effects of Sports-Related Concussion:
      Video-Oculography in Assessing Sports-Related Concussion.
AB  - OBJECTIVE: The purpose of the study was to test the ability of oculomotor,
      vestibular, and reaction time (OVRT) metrics to serve as a concussion assessment
      or diagnostic tool for general clinical use. SETTING AND PARTICIPANTS: Patients
      with concussion were high school-aged athletes clinically diagnosed in a hospital
      setting with a sports-related concussion (n = 50). Control subjects were
      previously recruited male and female high school student athletes from 3 local
      high schools (n = 170). DESIGN: Video-oculography was used to acquire eye
      movement metrics during OVRT tasks, combined with other measures. Measures were
      compared between groups, and a subset was incorporated into linear regression
      models that could serve as indicators of concussion. MEASURES: The OVRT test
      battery included multiple metrics of saccades, smooth pursuit tracking,
      nystagmoid movements, vestibular function, and reaction time latencies. RESULTS:
      Some OVRT metrics were significantly different between groups. Linear regression
      models distinguished control subjects from concussion subjects with high
      accuracy. Metrics included changes in smooth pursuit tracking, increased reaction
      time and reduced saccade velocity in a complex motor task, and decreased
      optokinetic nystagmus (OKN) gain. In addition, optokinetic gain was reduced and
      more variable in subjects assessed 22 or more days after injury. CONCLUSION:
      These results indicate that OVRT tests can be used as a reliable adjunctive tool
      in the assessment of concussion and that OKN results appear to be associated with
      a prolonged expression of concussion symptoms.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.

PMID- 30234849
TI  - Using Decision Tree Methodology to Predict Employment After Moderate to Severe
      Traumatic Brain Injury.
AB  - OBJECTIVE: To build decision tree prediction models for long-term employment
      outcomes of individuals after moderate to severe closed traumatic brain injury
      (TBI) and assess model accuracy in an independent sample. SETTING: TBI Model
      Systems Centers. PARTICIPANTS: TBI Model Systems National Database participants
      injured between January 1997 and January 2017 with moderate to severe closed TBI.
      Sample sizes were 7867 (year 1 postinjury), 6783 (year 2 postinjury), and 4927
      (year 5 postinjury). DESIGN: Cross-sectional analyses using flexible
      classification tree methodology and validation using an independent subset of TBI
      Model Systems National Database participants. MAIN MEASURES: Competitive
      employment at 1, 2, and 5 years postinjury. RESULTS: In the final employment
      prediction models, posttraumatic amnesia duration was the most important
      predictor of employment in each outcome year. Additional variables consistently
      contributing were age, preinjury education, productivity, and occupational
      category. Generally, individuals spending fewer days in posttraumatic amnesia,
      who were competitively employed preinjury, and more highly educated had better
      outcomes. Predictability in test data sets ranged from a C-statistic of 0.72
      (year 5; confidence interval: 0.68-0.76) to 0.77 (year 1; confidence interval:
      0.74-0.80). CONCLUSION: An easy-to-use decision tree tool was created to provide
      prognostic information on long-term competitive employment outcomes in
      individuals with moderate to severe closed TBI. Length of posttraumatic amnesia,
      a clinical marker of injury severity, and preinjury education and employment
      status were the most important predictors.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.

PMID- 30234850
TI  - Pharmaco-fMRI in Patients With Traumatic Brain Injury: A Randomized Controlled
      Trial With the Monoaminergic Stabilizer (-)-OSU6162.
AB  - OBJECTIVE: To examine the effects of monoaminergic stabilizer (-)-OSU6162 on
      brain activity, as measured by blood-oxygen-level-dependent (BOLD) functional
      magnetic resonance imaging (fMRI), in patients in the chronic phase of traumatic
      brain injury suffering from fatigue. SETTING: Neurorehabilitation clinic.
      PARTICIPANTS: Patients with traumatic brain injury received either placebo (n =
      24) or active treatment (n = 28). Healthy controls (n = 27) went through fMRI
      examination at one point and were used in sensitivity analysis on normalization
      of BOLD response. DESIGN: Randomized, double-blinded, placebo-controlled design.
      MAIN MEASURES: Effects on BOLD signal changes from before to after treatment
      during performance of a fatiguing attention task. RESULTS: The fMRI results
      revealed treatment effects within the right occipitotemporal cortex and the right
      orbitofrontal cortex. In these regions, the BOLD response was normalized relative
      to healthy controls at the postintervention fMRI session. No effects were seen in
      regions in which we previously observed activity differences between patients and
      healthy controls while performing this fMRI task, such as the striatum.
      CONCLUSION: (-)-OSU6162 treatment had influences on functional brain activity,
      although the normalized regional BOLD response was observed in regions that were
      not a priori hypothesized to be sensitive to this particular treatment, and was
      not accompanied by any effects on in-scanner test performance or on fatigue.

PMID- 30234851
TI  - Diagnostic and Therapeutic Challenges.

PMID- 30234852
TI  - SUBCLINICAL MACULAR CHANGES AND DISEASE LATERALITY IN PEDIATRIC COATS DISEASE
      DETERMINED BY QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB  - PURPOSE: To determine vascular change at the macula in both eyes in unilateral
      pediatric Coats disease using optical coherence tomography angiography. METHODS:
      Retrospective case-series. Thirteen eyes of pediatric patients with a diagnosis
      of unilateral Coats disease of various stages were compared with 13 fellow eyes.
      Optical coherence tomography angiography images were acquired using the RTVue XR
      Avanti. Scans were analyzed with novel projection artifact removal software and
      improved segmentation. Vascular density and foveal avascular zone area were
      calculated. RESULTS: Vascular density was significantly decreased in eyes with
      Coats disease in comparison with fellow eyes in both the superficial capillary
      plexus and deep capillary plexus (43.7 +/- 4.7 vs. 45.9 +/- 4.4 [P = 0.000] and
      43.0 +/- 6.3 vs. 50.3 +/- 2.2 [P = 0.001], respectively). The difference was also
      significant for most sectors of the macula. Foveal avascular zone area was
      significantly larger in eyes with Coats disease in comparison with fellow eyes
      (0.29 +/- 0.1 vs. 0.24 +/- 0.09 [P = 0.003]). These significant differences
      appeared as early as Stage 2A, preceding clinical findings. CONCLUSION: The
      findings support the unilaterality of Coats disease and show that vascular
      changes on optical coherence tomography angiography precede clinical staging of
      the condition.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.

PMID- 30234853
TI  - FIVE-YEAR FUNCTIONAL OUTCOMES AFTER EPIRETINAL MEMBRANE SURGERY: A Prospective,
      Controlled Study.
AB  - PURPOSE: To evaluate 5-year functional outcomes involving the inner retina after
      epiretinal membrane (ERM) surgery. METHODS: The study eye (SE) and fellow eye
      (FE) of 20 patients undergoing ERM surgery were examined preoperatively and at 3,
      12, 24, 36, 48, and 60 months postoperatively. Retinal nerve fiber layer and
      ganglion cell-inner plexiform layer (GC-IPL) thicknesses were analyzed using
      spectral domain optical coherence tomography. Humphrey visual field mean
      deviation, pattern SD, and qualitative changes were assessed and compared over
      time. RESULTS: Mean GC-IPL thickness in SEs was less than that of FEs at all time
      points with progressive thinning in SEs after ERM surgery. There was significant
      thinning of the superotemporal GC-IPL in SEs as compared to FEs at 3 months and
      60 months (P < 0.05). Humphrey visual field mean deviation was greater in SEs as
      compared to FEs but statistically significant only at 0, 12, and 24 months (P <
      0.05). Pattern SD increased from baseline in SEs but remained near baseline in
      FEs. CONCLUSION: Surgical eyes after ERM surgery demonstrated progressive
      thinning of the GC-IPL and transient worsening trends in Humphrey visual field
      mean deviation and pattern SD as compared to controls after ERM surgery.

PMID- 30234854
TI  - MICROPERIMETRY AS A SCREENING TEST FOR HYDROXYCHLOROQUINE RETINOPATHY: The Hard
      Risk-1 Study.
AB  - PURPOSE: To assess the sensitivity and specificity of microperimetry as a
      screening test to detecting hydroxychloroquine retinopathy. METHODS:
      Retrospective cohort study. Patients with history of hydroxychloroquine use for
      more than 5 years and with concomitant microperimetry and multifocal
      electroretinogram testing were retrospectively reviewed. Microperimetry was
      considered positive if there were three or more contiguous scotoma points in the
      parafoveal region. Multifocal electroretinogram was used as gold standard and was
      considered positive if there was an increased R1/R2 ring ratio (>2.5) or reduced
      R1 absolute amplitude (<9.0). Sensitivity, specificity, positive predictive
      value, and negative predictive value of microperimetry were calculated. RESULTS:
      A total of 197 patients were reviewed. Hydroxychloroquine retinopathy was present
      in 22 (11%) patients. Their mean (SD) age was 54 (14) years, and 96% were women.
      Their mean (SD) daily dose was 5.7 (1.3) mg/kg, cumulative dose was 2041 (1,548)
      g, and duration of use was 15 (10) years. Sensitivity, specificity, positive
      predictive value, and negative predictive value of microperimetry were 73%, 93%,
      53%, and 96%, respectively. CONCLUSION: Microperimetry has inferior sensitivity
      but good specificity in detecting hydroxychloroquine retinopathy (compared with
      multifocal electroretinogram). As such, it may be a useful ancillary test to
      exclude retinopathy, especially in high-risk patients or those with conflicting
      results on different modalities.

PMID- 30234855
TI  - EFFECT OF SERIAL ANTERIOR CHAMBER PARACENTESIS ON SUSTAINED INTRAOCULAR PRESSURE
      ELEVATION IN PATIENTS RECEIVING INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH
      FACTOR THERAPY.
AB  - PURPOSE: To investigate the effect of serial anterior chamber (AC) paracenteses
      in eyes with sustained elevations of intraocular pressure (IOP) in the setting of
      repeated intravitreal injections (IVI) of anti-vascular endothelial growth factor
      medications. METHODS: This is a retrospective records review of patients
      undergoing IVI of anti-vascular endothelial growth factor medication
      (bevacizumab, ranubizumab, or aflibercept), who demonstrated a sustained
      elevation of preinjection IOP and also received AC paracentesis immediately after
      IVI on at least three consecutive visits. Changes in preinjection IOP and cup-to
      disk (C:D) ratio were compared before and after the initiation of IVI and before
      and after the introduction of AC paracenteses with each subsequent IVI. RESULTS:
      Twenty-three eyes of 17 patients receiving a median of 26 IVI experienced a rise
      in preinjection IOP from 16.3 mmHg to 21.1 mmHg (P = 0.004) and an increase in
      mean C:D ratio from 0.37 to 0.47 (P = 0.0002). After introduction of AC
      paracenteses (median of 12), mean IOP was returned to baseline 16.00 mmHg (P =
      0.002), mean C:D ratio stabilized (0.50, P = 0.197), and maximum IOP decreased
      from 26.8 mmHg to 23.0 mmHg (P = 0.05). Nineteen (82.6%) eyes required an
      increase in topical glaucoma medications during the study period, and 13 (56.5%)
      still required additional therapies after initiation of AC paracenteses. Five
      eyes (38.5%) required laser or glaucoma drainage device procedures. CONCLUSION:
      Serial AC paracenteses reduced immediate postinjection IOP, and along with
      standard glaucoma care in most patients, reversed preinjection IOP elevation, and
      stabilized optic nerve changes associated with repeated intravitreal anti
      vascular endothelial growth factor injections in a subset of patients with
      sustained elevation of preinjection IOP.

PMID- 30234856
TI  - Argus II Retinal Prosthesis Implantation Using Three-Dimensional Visualization
      System.

PMID- 30234857
TI  - Fingolimod-Associated Retinal Hemorrhages and Roth Spots.

PMID- 30234858
TI  - Diffuse Infiltrating Retinoblastoma.

PMID- 30234859
TI  - CHANGES IN DIABETIC RETINOPATHY SEVERITY WHEN TREATING DIABETIC MACULAR EDEMA
      WITH RANIBIZUMAB: DRCR.net Protocol I 5-Year Report.
AB  - PURPOSE: To explore 5-year changes from baseline in diabetic retinopathy severity
      among eyes treated with ranibizumab for diabetic macular edema. METHODS: Diabetic
      retinopathy severity was assessed from study visits and annual fundus photographs
      among participants in Protocol I (DRCR.net). The proportion of eyes that improved
      at annual examinations and the cumulative probability of worsening through 5
      years were estimated. RESULTS: Among 235 participants with nonproliferative
      diabetic retinopathy at baseline, there were 29%, 28%, and 32% of eyes with
      retinopathy improvement at 1, 3, and 5 years, respectively. Among 111
      participants with proliferative diabetic retinopathy, corresponding improvement
      percentages were 38%, 35%, and 23%. The 5-year cumulative probability of
      worsening was 18% (95% CI: 14%-25%) among nonproliferative diabetic retinopathy
      eyes and 31% (95% CI: 23%-42%) among proliferative diabetic retinopathy eyes (P =
      0.01). In Years 1, 3, and 5, the mean (SD) number of ranibizumab injections was
      8.1 (2.5), 2.2 (2.6), and 1.8 (2.6) for nonproliferative diabetic retinopathy
      eyes, and 9.0 (2.8), 2.3 (2.9), and 1.7 (2.6) for proliferative diabetic
      retinopathy eyes, respectively. Proportions with improvement or rates of
      worsening did not change with time. CONCLUSION: Individuals receiving ranibizumab
      therapy for diabetic macular edema may have favorable changes in DR severity
      throughout a 5-year period concomitant with sequential reduction in anti-vascular
      endothelial growth factor therapy.

PMID- 30234860
TI  - Exploration of the synthesis of three types of multicolor carbon dot originating
      from isomers.
AB  - Currently, the synthesis of carbon dots (CDs) exhibiting long-wavelength emission
      is still challenging. Herein, we have synthesized for the first time three types
      of CD with multicolor emission derived from isomers. Importantly, their particle
      size, nitrogen-doping amount and band gaps collectively regulate the fluorescence
      emission of the proposed CDs.

PMID- 30234861
TI  - Introduction of various substitutions to the methine bridge of heptamethine
      cyanine dyes Via substituted dianil linkers.
AB  - The unique optical properties of cyanine dyes have prompted their use in numerous
      applications. Heptamethine cyanines are commonly modified on the methine bridge
      after synthesis of a meso-chlorine containing cyanine. Herein, a series of
      heptamethine cyanines containing modified methine bridges were synthesized using
      substituted dianil linkers. Their optical properties including, molar
      absorptivity, fluorescence, and quantum yield were measured as well as their
      hydrophobic effects in polar buffer solution. It was shown that dyes containing
      cyclopentene in the methine bridge or a phenyl ring in the meso position display
      increased molar absorptivity while the increased flexibility of the dye
      containing a cycloheptene in the methine bridge prevented fluorescence.

PMID- 30234862
TI  - Highly efficient and selective visible-light driven CO2-to-CO conversion by a Co
      based cryptate in H2O/CH3CN solution.
AB  - Herein, we report a mononuclear Co(ii) cryptate which exhibits highly efficient
      and selective photocatalytic CO2-to-CO conversion in H2O/CH3CN solution. The TON
      and selectivity reach as high as 51 392 and 98%, respectively.

PMID- 30234863
TI  - From fundamentals to applications: a toolbox for robust and multifunctional MOF
      materials.
AB  - In recent years, metal-organic frameworks (MOFs) have been regarded as one of the
      most important classes of materials. The combination of various metal clusters
      and ligands, arranged in a vast array of geometries has led to an ever-expanding
      MOF family. Each year, new and novel MOF structures are discovered. The
      structural diversity present in MOFs has significantly expanded the application
      of these new materials. MOFs show great potential for a variety of applications,
      including but not limited to: gas storage and separation, catalysis, biomedicine
      delivery, and chemical sensing. This review intends to offer a short summary of
      some of the most important topics and recent development in MOFs. The scope of
      this review shall cover the fundamental aspects concerning the design and
      synthesis of MOFs and range to the practical applications regarding their
      stability and derivative structures. Emerging trends of MOF development will also
      be discussed. These trends shall include multicomponent MOFs, defect development
      in MOFs, and MOF composites. The ever important structure-property-application
      relationship for MOFs will also be investigated. Overall, this review provides
      insight into both existing structures and emerging aspects of MOFs.

PMID- 30234864
TI  - Caged siRNAs with single folic acid modification of antisense RNA for
      photomodulation of exogenous and endogenous gene expression in cells.
AB  - Manually controlling siRNA activity is an essentially important way to
      spatiotemporally investigate gene expression and function. Owing to ease of
      operation and precise manipulation, light can be used for controlled regulation
      of siRNA-induced gene silencing. Here, we developed a series of caged siRNAs with
      folic acid modification at the 5' terminus of the antisense strand of the siRNA
      through a photolabile linker. The attachment of the folic acid moiety temporarily
      masked the corresponding siRNA activity. Upon illumination, these caged siRNAs
      were activated, and their gene silencing activities were restored. Based on this
      strategy, we successfully photomodulated gene expression of both an exogenous
      gene (for green fluorescent protein, GFP) and an endogenous gene (for mototic
      kinesin-5, Eg5) in cells.

PMID- 30234865
TI  - Rhodium(iii)-catalyzed dehydrogenative dialkenylation of the monocarba-closo
      decaborate cluster by regioselective B-H activation.
AB  - closo-Boranes and closo-carboranes, clusters with a closed-cage structure,
      exhibit remarkable inertness and are unique components of products with
      applications in areas such as medicinal chemistry, fluorescence and materials
      science. Herein, we report the first transition metal-catalyzed functionalization
      of the mono-closo-decaborate cluster [1-CB9H10]- by regioselective B-H
      activation. Using terminal alkenes bearing a wide range of functional groups,
      dehydrogenative coupling under mild conditions leads to B2/3-dialkenylated
      products, as verified by X-ray crystallography and NMR studies. This substitution
      pattern has not been accessible by other methods and enables the straightforward
      synthesis of new derivatives of the {CB9} cluster.

PMID- 30234866
TI  - Protic additives determine the pathway of CdSe nanocrystal growth.
AB  - The formation of semiconductor nanocrystals by hot-injection synthesis follows
      complex reaction mechanisms that are not yet fully understood. In particular the
      occurrence of intermediate species indicated by sharp, stationary spectral lines
      poses an important deviation from the predictions of classical nucleation theory.
      We show that trace amounts of water and other protic additives strongly impact
      the structure of these reaction intermediates, forming either coordination
      polymers under dry conditions or small clusters in the presence of moisture.
      These intermediates bind monomer during the initial nucleation phase. The
      structure of the intermediate determines the monomer release rate, either
      continuously or in a rapid dissolution event, and hence controls the reaction
      kinetics. From this we propose a kinetic model that allows us to predict
      secondary nucleation events. By directing the type of intermediate formed, protic
      additives provide a lever to manipulate this equilibrium and control nanocrystal
      synthesis in a rational fashion.

PMID- 30234867
TI  - Selective formation of a two-dimensional coordination polymer based on a
      tridentate phospholane ligand and gold(i).
AB  - The tridentate phosphine ligand 1,3,5-tris[(E)-(4-phospholano-2,6
      diethyl)styryl]benzene (1) reacts with [AuCl(tht)] (tht = tetrahydrothiophene)
      independent of the stoichiometry employed with selective formation of a two
      dimensional coordination polymer (ratio 1 : 1) with the gold(i) cations in a
      trigonal-planar [3 + 1] coordination geometry. Each of the three coordinating
      phosphine units originates from another ligand, thus forming a polymeric
      structure.

PMID- 30234868
TI  - Ultrastability and color-tunability of CsPb(Br/I)3 nanocrystals in P-Si-Zn glass
      for white LEDs.
AB  - A series of CsPbBrxI3-x NC glasses, showing tunable emission (523-693 nm)
      controlled by different ratios of Br- and I-, were successfully prepared. The
      CsPbBrxI3-x NC glasses exhibited excellent optical properties and outstanding
      stability towards ambient conditions, water and heat.

PMID- 30234869
TI  - A G4.K+ hydrogel made from 5'-hydrazinoguanosine for remediation of alpha,beta
      unsaturated carbonyls.
AB  - A G4.K+ hydrogel made from 5'-hydrazinoguanosine and KCl reacts with alpha,beta
      unsaturated carbonyls of different electrophilicities (acrolein, methyl vinyl
      ketone and methyl acrylate) in water and the gas phase to form cyclic adducts.
      This aza-Michael addition/cyclization domino reaction by the 5'-hydrazino G4.K+
      hydrogel has promise for environmental remediation of toxic alpha,beta
      unsaturated carbonyls from water and the atmosphere.

PMID- 30234870
TI  - Photocatalytic abatement of emerging pollutants in pure water and wastewater
      effluent by TiO2 and Ce-ZnO: degradation kinetics and assessment of
      transformation products.
AB  - Here, the performances of two different catalysts, Ce-ZnO and TiO2 synthetized in
      our laboratories, were compared with the commercial TiO2-P25 for degradation of a
      mixture of seven emerging pollutants under UV irradiation. The investigation
      included monitoring pollutants abatement in Milli-Q water and in wastewater
      effluent and identifying their transformation products by HPLC-HRMS. Structural
      characterization of intermediates supported by data available from literature
      allowed elucidation of the transformation pathways occurring in the presence of
      all investigated catalysts in the wastewater effluent. Preliminary results showed
      a good removal efficacy for almost all examined contaminants, even in real water
      matrix (i.e. wastewater effluent). The type of matrix and catalyst affects the
      number and/or the abundance of transformation products, which suggests
      differences in their transformation routes.

PMID- 30234871
TI  - Reversible DNA compaction induced by partial intercalation of 16-Ph-16 gemini
      surfactants: evidence of triple helix formation.
AB  - The interaction between calf thymus DNA and the gemini surfactants N,N'
      [alpha,omega-phenylenebis(methylene)bis [N,N'-dimethyl-N-(1-hexadecyl)]-ammonium
      dibromide], p-16-Ph-16 (alpha = 1, omega = 3) and m-16-Ph-16 (alpha = 1, omega =
      2), has been investigated via circular dichroism, fluorescence and UV-vis
      spectroscopy, zeta potential, dynamic light scattering, and AFM microscopy.
      Measurements were carried out in aqueous media at different molar ratios, R =
      (C16-Ph-16)/CDNA and C16-Ph-16 always below the critical micellar concentration
      (CMC) of the surfactant. Under these conditions, DNA undergoes two reversible
      conformational changes, compaction and decompaction, due to interaction with the
      surfactant molecules at low and high molar ratios, respectively. The extent of
      such conformational changes is correlated with both the degree of surfactant
      partial intercalation, and the size and charge of the surfactant aggregates
      formed, in each case. Comparison of the results shows that the para-form of the
      surfactant intercalates into the DNA to a major extent; therefore, the
      compaction/decompaction processes are more effective. Among these, the structure
      of the resulting 16-Ph-16/DNA decompacted complex is worthy of note. For the
      first time it can be demonstrated that the partial intercalation of the 16-Ph-16
      gemini surfactants induces the formation of triplex DNA-like structures at a high
      R ratio.

PMID- 30234873
TI  - Teaching from the primary inorganic literature: lessons from Richard Andersen.
AB  - For many who passed through his classroom, Richard Andersen demonstrated how
      inorganic chemistry can be taught by incorporating the research literature. The
      Interactive Online Network of Inorganic Chemists (IONiC) through its website and
      summer workshops for faculty has supported the development and sharing of more
      than a hundred exercises or "learning objects" derived from articles highlighting
      research across the inorganic field. Faculty can adapt and implement these
      learning objects in their own classrooms to achieve goals such as demonstrating
      historical context, teaching course material via current research, and
      elaborating on the scientific process. Literature discussion learning objects
      highlight current and past research in inorganic chemistry and teach students
      both chemistry content and how the body of inorganic knowledge is constructed.

PMID- 30234872
TI  - Transcellular delivery of messenger RNA payloads by a cationic supramolecular MOF
      platform.
AB  - A supramolecular catiomer with a metal-organic framework (MOF) motif was
      developed to manufacture messenger RNA (mRNA) assemblies. In contrast to the
      linear catiomer, the dendritic MOF catiomer appeared to markedly improve the
      colloidal stability of the mRNA assemblies, particularly affording substantial
      protection to the mRNA payloads from enzymatic degradation, eventually conducing
      to appreciable mRNA transfection activities at the targeted cells.

PMID- 30234878
TI  - The role of alkalinity in setting water quality metrics: phosphorus standards in
      United Kingdom rivers.
AB  - UK implementation of the European Union Water Framework Directive (for the 2015
      2021 cycle) Ecological Status (ES) classification for river phosphorus is based
      on the calculation of reference conditions for reactive phosphorus (RP) using
      river alkalinity measurements. Underpinning this approach is that the alkalinity
      is primarily from rock weathering and is free of anthropogenic influences.
      However, the potential contribution of anthropogenic alkalinity needs to be
      considered and, if possible, quantified. In the rural South West River Basin
      District of England, 38 river sites were examined with respect to river
      alkalinity loads in order to test this consideration. At river base flow when RP
      can cause enhanced algal growth, 9 sites (24%) had effluent alkalinity
      contributions amounting to 25-49% of the total riverine alkalinity load, while 11
      (29%) of the sites received >=50% of their alkalinity load from effluent. When
      flows increased above base flow to Q95 flow at these 11 sites, catchment diffuse
      run-off became the largest load of alkalinity at 9 of the sites, and that at the
      Q95 flows, combined effluent and diffuse alkalinity loads contributed 68-100% of
      the total alkalinity load. Anthropogenic alkalinity is likely to be present in
      diffuse run-off, but it is difficult to apportion alkalinity loads between
      natural and contaminant sources. It is likely that diffuse loads of alkalinity
      will dominate on the annual timescales used to assess WFD compliance, even at
      sites where ground water alkalinity dominates at base river flows. In principle,
      inclusion of anthropogenic alkalinity in the calculation of ES boundary
      concentrations for RP may lead to a relaxation of the standards. In practice this
      may not follow. It is likely that at the river sites used initially to develop
      the algorithms now used for P standard setting, anthropogenic alkalinity was
      present, to varying and unknown degrees, and that this alkalinity would have
      influenced the measured and reference RP and biological metrics on which the P
      standards are based. Apart from RP, alkalinity is also used to underpin water
      quality metrics for additional chemical and biological parameters, and for this
      reason, understanding the complex factors determining river alkalinity loads
      should be an important task for water quality regulators.

PMID- 30234879
TI  - Reverse relationships of water uptake and alkaline durability with hydrophilicity
      of imidazolium-based grafted anion-exchange membranes.
AB  - We found unprecedented reverse relationships in anion-exchange membranes (AEMs)
      for Pt-free alkaline fuel cell systems, i.e., the increase in hydrophobicity
      increased water uptake and susceptibility to hydrolysis. AEMs with graft
      copolymers that composed of anion-conducting 2-methyl-N-vinylimidazolium (Im) and
      hydrophobic styrene (St) units were employed. We characterized two new structures
      in these AEMs using a small-angle neutron scattering with a contrast variation
      method. (1) The distribution of graft polymers in conducting (ion channel) or non
      conducting (hydrophobic amorphous poly(ethylene-co-tetrafluoroethylene) (ETFE))
      phase was evaluated in a quantitative manner. High fraction in conducting layer
      for AEMs having high grafting degrees was found using the proposed structural
      model of "conducting/non-conducting two-phase system". (2) Assuming a hard-sphere
      fluid model, we found AEMs having high St contents and low alkaline durability
      possessed nanophase-separated water puddles with diameters of 3-4 nm. The AEM
      having a low St content and the best alkaline durability did not show evident
      nanophase separation. The above hierarchical structures elucidate the unexpected
      reverse relationships that the AEM having highly hydrophobic graft polymers was
      subjected to the morphological transition to give water puddles at nanoscale. The
      imidazolium groups that were located at the boundary between graft polymers and
      water puddles should be susceptible to hydrolysis.

PMID- 30234880
TI  - Integrative and Complementary Practices in the Unified Health System: progresses
      and challenges.

PMID- 30234881
TI  - Factors associated with the quality of the diet of residents of a rural area in
      Southern Brazil.
AB  - OBJECTIVE: To identify factors associated with a better quality of the diet of
      residents of a rural area in Southern Brazil. METHODS: This is a population
      based, cross-sectional study with individuals aged 18 years or over living in the
      rural area of Pelotas, State of Rio Grande do Sul, Brazil. Food consumption was
      evaluated by a food frequency questionnaire of thirteen items, related to the
      consumption in the last week. We evaluated quality of the diet using the Adult
      Diet Quality Index (IQD-A). Healthy food received increasing scores while
      unhealthy food received decreasing scores, according to consumption frequency,
      amounting to scores from zero to 30. The total score was divided into tertiles.
      Individuals of the third tertile were classified with better quality of the diet.
      We investigated the association between quality of the diet and independent
      variables using multinomial logistic regression. RESULTS: We interviewed 1,519
      individuals with mean IQD-A of 17.1 points (SD = 3.3) and a median of 17.0 (range
      of 10 to 25 points). Although the population studied kept the consumption of
      staple foods, the intake of industrialized food such as soft drinks, artificial
      juices, and unhealthy foods such as sweets was high. Older individuals presented
      seven times (95%CI 4.20-12.48) more chance of having a better quality of the
      diet. Women, individuals with higher economic status, those who worked in the
      sale of animals, or those who had diabetes were approximately twice as likely to
      be in the group with the best quality of the diet. Individuals whose families
      worked with fishing presented a 70% lower chance of being in the group of better
      quality of the diet. CONCLUSIONS: We identified that men, younger adults,
      individuals of lower socioeconomic level, and fishing families were in the group
      of higher vulnerability for the consumption of a diet with worse quality. Thus,
      public policies, especially educational policies, are needed to promote healthy
      eating in this group.

PMID- 30234882
TI  - Epidemiology of smoking in the rural area of a medium-sized city in Southern
      Brazil.
AB  - OBJECTIVE: To estimate the prevalence of smoking and associated factors among
      rural residents. METHODS: This is a population-based, cross-sectional study of
      1,519 individuals carried out in 2016. We randomly selected 24 of the 50 census
      tracts that make up the eight rural districts of the city of Pelotas, State of
      Rio Grande do Sul, Brazil. All individuals aged 18 years or more living in the
      randomly selected households were eligible. Smokers were all those who smoked >=
      1 cigarette/day for at least one month or declared that they had stopped smoking
      for less than one month. The independent variables included socioeconomic,
      demographic, behavioral, and health characteristics. We investigated age of
      onset, duration of addiction, number of cigarettes smoked/day, pack-years, and
      types of cigarettes consumed. Poisson regression was performed to calculate the
      adjusted prevalence ratios (PR) and 95% confidence intervals (95%CI). RESULTS:
      The prevalence of smoking was 16.6% (95%CI 13.6-20.0), and it was twice as high
      in men in relation to women (PR = 1.99, 95%CI 1.44-2.74), in socioeconomic class
      D or E in relation to class A or B (PR = 2.23, 95%CI 1.37-3.62), and in those who
      considered their health poor or very poor in relation those with good or very
      good health (PR = 2.02, 95%CI 1.33-3.08). It was also higher in persons aged 30
      59 years (compared to those aged < 30 years), with 5-8 years of education level
      (compared to those with >= 9 years), and with positive screening for alcohol
      related disorder. Prevalence was lower among individuals who were overweight or
      obese than in those with normal weight. Smoking began on average at 16.9 years,
      with an average consumption of approximately 14 cigarettes/day and mean pack
      years of 22 packs/year. The paper hand-rolled cigarette was the most consumed
      (57.6%). CONCLUSIONS: Approximately one in six adults in rural Pelotas is a
      current smoker. The findings show the existence of social inequalities related to
      smoking addiction. Actions to prevent and control smoking should continue to be
      stimulated, especially in the most vulnerable subgroups.

PMID- 30234884
TI  - Spatial risk of death in patients with AIDS in Campinas, Sao Paulo, Brazil.
AB  - OBJECTIVE: To analyze the spatial risk of AIDS mortality in census tracts in a
      large Brazilian city. METHOD: We studied three retrospective cohorts of
      individuals with AIDS, who were residents in the city of Campinas, in the State
      of Sao Paulo, Brazil. The occurrence of death was analyzed from 1980 to 1990
      (cohort 1), 1996 to 2000 (cohort 2), and from 2001 to 2005 (cohort 3). We
      adjusted a Bayesian semi-parametric model, using the Integrated Nested Laplace
      Approximation (INLA) method, which allowed for the mapping of mortality risk for
      the three cohorts. RESULTS: The incidence of death in cohorts 1, 2 and 3 were,
      respectively, 72.73, 32.21 and 13.11%. The death risk maps showed a tendency of
      mortality decrease, and presented the sectors with the highest and lowest risk
      for each period. The model showed that, in the three cohorts, factors associated
      with the highest risk of death were: being male, and having an age at diagnosis
      greater than 49 years old. The homosexual/bisexual orientation was associated
      with lower risk of dying. CONCLUSIONS: Even considering the reduction in the risk
      of death from AIDS in recent years, after access to highly active antiretroviral
      therapy, the highest incidence was found among the poorest individuals in the
      three studied cohorts. The maps and risk factors obtained suggest possible
      actions for monitoring the disease in the city.

PMID- 30234883
TI  - Population-based study in a rural area: methodology and challenges.
AB  - OBJECTIVE: To describe the planning, sampling, operational aspects of the field,
      and the sample obtained during a research conducted in a rural area, specifying
      and discussing the main logistical difficulties unique to these places and the
      solutions adopted. METHODS: We carried out a population-based, cross-sectional
      survey between January and June 2016, with a representative sample of the
      population aged 18 years or over living in the rural area of Pelotas
      (approximately 22,000 individuals), State of Rio Grande do Sul, Brazil. We
      collected demographic, socioeconomic, and health-related information, such as
      alcohol consumption, cigarette consumption, depressive symptoms, quality of diet,
      quality of life, physical activity, satisfaction with the health unit, overweight
      or obesity, and sleep problems. RESULTS: In the 720 domiciles sampled, 1,697
      individuals were identified and 1,519 were interviewed (89.5%). The study
      initially drew 24 census tracts and proposed the visit to 42 households per
      tract; however, we need to adjust the method, such as decreasing the number of
      households per census tract (from 42 to 30) and identifying housing centers in
      each tract. The main reasons for these changes were difficulty accessing the
      area, large distances between households, misconceptions in the satellite data
      available (which did not fit the reality), and high cost of the field work.
      CONCLUSIONS: The previous detailed recognition of the research environment was
      crucial for decision making as the maps and territory had geographical
      inconsistencies. The strategies and techniques used in studies for the urban area
      are not applicable to the rural area given the outcomes observed in Pelotas. The
      decisions taken, keeping the methodological rigor, were essential to ensure the
      timely execution of the study with the financial resources available.

PMID- 30234885
TI  - Subjective well-being, religiosity and anxiety: a cross-sectional study applied
      to a sample of Brazilian medical students.
AB  - OBJECTIVE: To assess associations between subjective well-being (SWB),
      religiosity, anxiety and other factors in a sample of Brazilian medical students
      from a public university in northeastern Brazil. METHODS: The present study
      followed a cross-sectional, observational, analytical approach. Data were
      collected by administering a self-applicable questionnaire composed of questions
      focused on sociodemographic data and based on the Satisfaction With Life Scale
      (SWL), Positive Affect and Negative Affect Scale (PANAS), Penn State Worry
      Questionnaire (PSWQ), and the Duke Religiosity Index (DUREL). RESULTS: The sample
      comprised 417 medical school students (73.54% of all the enrolled students). The
      medical students assessed presented a medium level of satisfaction with life, low
      mean positive emotion levels and high anxiety/uneasiness levels. Surprisingly,
      lower anxiety and intrinsic religiosity (IR) scores were associated with higher
      scores in the two SWB parameters (positive emotions and satisfaction with life).
      Furthermore, the factors leisure activities, good sleep quality, financial
      support, age, and gender were associated with the highest SWB scores (with
      emotional and cognitive components, or with only one of these two components).
      CONCLUSIONS: Data in the current study corroborated the negative association
      between SWB and anxiety; however, in opposition to the literature, they also
      evidenced a negative association between SWB and IR. In addition, the present
      research signaled the need for creating preventive intervention programs to
      increase SWB through positive psychological techniques and/or to decrease anxiety
      by applying, for instance, cognitive-behavioral therapy paradigms and/or
      mindfulness techniques to medical students.

PMID- 30234886
TI  - Characterization of neurological soft signs in a Brazilian sample of stable
      patients with schizophrenia.
AB  - INTRODUCTION: Neurological soft signs (NSS) have been considered one of the
      target features and a potential endophenotype for schizophrenia. The present
      study aimed to characterize NSS in a sample of patients with chronic
      schizophrenia and to compare them with healthy control individuals. METHODS: In
      this study, we evaluated the presence of NSS in a sample of stable patients (n =
      24) diagnosed with schizophrenia according to DSM-IV criteria, recruited at the
      Schizophrenia Outpatient Clinic of Instituto Raul Soares, Belo Horizonte, state
      of Minas Gerais, southeastern Brazil. Assessment was made with the Brief Motor
      Scale (BMS), and extrapyramidal symptoms (EPS) were evaluated with the Simpson
      Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS). A control
      group (n = 21) was also submitted to the same battery of tests. RESULTS: We
      observed a significant difference in relation to BMS and SAS scores (p < 0.0001),
      revealing that individuals with schizophrenia present more NSS and EPS than
      healthy ones. BMS total scores correlated positively with SAS scores (r = 0.495,
      p = 0.014), but not with AIMS scores, indicating that NSS could be influenced by
      the intensity of EPS. Nevertheless, we observed that this relationship remained
      only for motor coordination tasks (r = 0.550, p = 0.005), while motor sequencing
      tasks were not influenced by EPS (r = 0.313, p = 0.136). CONCLUSION: The results
      suggest that NSS are more frequent in patients with schizophrenia and that motor
      sequencing tasks could be more specific to the syndrome.

PMID- 30234888
TI  - Transcultural adaptation to Portuguese of the Mind Excessively Wandering Scale
      (MEWS) for evaluation of thought activity.
AB  - INTRODUCTION: The concept of mind wandering refers to periods during which
      attention and content of thoughts depart from the original idea or activity being
      performed. The phenomenon occurs commonly in the general population and the Mind
      Wandering Excessively Scale (MEWS) evaluates its frequency, intensity and related
      negative outcomes. OBJECTIVE: To describe the cross-cultural adaptation of the
      MEWS. METHODS: Cross-cultural adaptation of the original scale followed five
      consecutive steps: translation, backtranslation, appreciation of semantic
      equivalence and administration to a convenience sample to 20 adults with
      attention deficit hyperactivity disorder (ADHD) and 20 normal controls. RESULTS:
      Results indicated a satisfactory equivalence between the original and translated
      versions. A synthesis version for Brazilian Portuguese is presented. CONCLUSIONS:
      MEWS provides information on thought activity, which is particularly important in
      ADHD cases. The Brazilian Portuguese version would be welcome to address specific
      treatment responses and obtain new outcome measures.

PMID- 30234887
TI  - Temporal discounting and attention-deficit/hyperactivity disorder in childhood:
      reasons for devising different tasks.
AB  - INTRODUCTION: Temporal discounting (TD) describes how a certain reward is seen as
      less valuable the more its delivery is postponed. There are two main types of TD
      tasks, hypothetical and real, both of which use monetary rewards. Over the last
      few years, however, variants of these tasks have been adjusted to assess clinical
      groups of children showing impulsivity as found in attention
      deficit/hyperactivity disorder (ADHD). OBJECTIVE: To review and discuss studies
      conducted over the last 10 years on the use of TD tasks in the assessment of
      pediatric patients with ADHD. METHOD: For this literature review, articles were
      non-systematically selected from PubMed, MEDLINE and SciELO databases to include
      experimental studies on the use of at least one TD paradigm to assess and
      distinguish ADHD and non-ADHD groups. RESULTS: Of the studies assessed, 76.19%
      used hypothetical tasks, followed by real tasks (28.57%), and, finally, tasks
      using different types of reward, such as toys or rewarding activities (14.28%).
      CONCLUSIONS: Although assessed in few studies, real and alternative tasks
      appeared to be effective in differentiating clinical groups and suitable for
      investigating hot executive functions in childhood.

PMID- 30234889
TI  - Psychometric properties of the Brazilian version of the Difficulties in Emotion
      Regulation Scale (DERS).
AB  - INTRODUCTION: Emotion regulation can be defined as the process by which
      individuals manage their emotional experience. It has been demonstrated that
      deficits in this ability are associated with various psychiatric disorders. In
      this direction, the Difficulties in Emotion Regulation Scale (DERS) was developed
      to measure difficulties in emotion regulation. OBJECTIVE: To examine the
      psychometric properties of the Brazilian Portuguese version of the DERS. METHOD:
      A total of 377 individuals from the general population, selected by convenience,
      completed a sociodemographic form, the adapted Brazilian Portuguese DERS and the
      Depression Anxiety Stress Scale (DASS-21). Factor structure, reliability, and
      concurrent validity of the adapted version of the instrument were investigated.
      RESULTS: The confirmatory factor analysis replicated the six-factor structure
      originally proposed for the instrument and confirmed the acceptability of a
      hierarchical model where all DERS subscales loaded on a general emotion
      dysregulation factor. Internal consistency indicators had adequate values for the
      general factor and subscales. The positive association between DERS and DASS-21
      scores supports the instrument's concurrent validity. CONCLUSION: These results
      suggest that the Brazilian version of the DERS is reliable both as a general
      measure of difficulties in emotion regulation and as a measure of the
      constituents of this construct. Future research should investigate the
      psychometric properties of the scale in clinical and nonclinical populations,
      with equal gender proportions and diverse backgrounds, and preferably employing
      longitudinal designs.

PMID- 30234890
TI  - Global hippocampal atrophy in major depressive disorder: a meta-analysis of
      magnetic resonance imaging studies.
AB  - INTRODUCTION: Major depressive disorder (MDD), an incapacitating mental disorder,
      is characterized by episodes of at least 2 weeks of apparent changes in mood,
      cognition, and neurovegetative functions. Many neuroimaging studies using
      magnetic resonance imaging (MRI) have examined morphometric changes in patients
      with MDD, but the results are not conclusive. This study aims to review the
      literature and perform a meta-analysis on hippocampal volume (HcV) in patients
      with MDD. METHODS: Studies on HcV in patients with MDD diagnosis were identified
      from major databases (MEDLINE, EMBASE, The Cochrane Library, Scopus, PsycINFO,
      and SciELO) using the search terms depression, major depressive disorder, MDD,
      unipolar, magnetic resonance imaging, MRI, and hippocampus. RESULTS: A meta
      analysis of 29 studies fulfilling specific criteria was performed. The sample
      included 1327 patients and 1004 healthy participants. The studies were highly
      heterogeneous with respect to age, sex, age of onset, and average illness
      duration. However, the pooled effect size of depression was significant in both
      hippocampi. MDD was associated with right (-0.43; 95% confidence interval [95%CI]
      -0.66 to -0.21) and left (-0.40; 95%CI -0.66 to -0.15) hippocampal atrophy.
      CONCLUSIONS: MDD seems to be associated with global HcV atrophy. Larger
      longitudinal follow-up studies designed to analyze the influence of
      sociodemographic variables on this relationship are required to yield better
      evidence about this topic.

PMID- 30234891
TI  - Characteristics of circulating endothelial cells obtained from non ST elevation
      myocardial infarction patients with additional diastolic dysfunction of left
      ventricle observed in echocardiography.
AB  - BACKGROUND: Circulating endothelial cells (CEC) may be used to find new
      strategies for the early diagnosis of cardiovascular diseases. The major
      objective of the project is to broaden knowledge of CEC biology by determining
      their phenotypic characteristics. The additional aim is to clarify whether on the
      basis of these information it is possible to identify the origin of CEC release
      (from various cardiovascular compartments). METHODS: Circulating endothelial
      cells were collected from arterial blood prior to angiography, as well as from
      arterial and venous blood obtained after angiography/coronary angioplasty, from
      18 patients with non-ST-segment elevation myocardial infarction (NSTEMI). CECs
      were quantified by flow cytometry and defined as Syto16 (dye)+, CD45dim/neg,
      CD31+ and CD146+. The additional CD36+ was establish as a marker of endothelial
      cells released from small vessels of the microcirculation. RESULTS: The total
      number of CECs increased significantly after the percutaneous transluminal
      coronary angioplasty in the arterial system. Number of CECs isolated at similar
      time points (after invasive procedure) did not differ significantly between
      arteries and veins, but the number of CD36+ CECs after coronary angioplasty was
      significantly higher in the venous system, than in the arterial system.
      CONCLUSIONS: The number of CD36+ in artery samples obtained after coronary
      angioplasty (PTCA) had tendency to be decreased (in comparison to the sample
      obtained before angiography). It was major difference between those who had PTCA
      performed vs. those who had not.

PMID- 30234892
TI  - Increased systemic arterial stiffness in patients with chronic thromboembolic
      pulmonary hypertension.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a
      complication of venous thromboembolism (VTE) resulting from non-dissolving
      thromboembolic in the pulmonary arteries. Previous observations indicate a higher
      prevalence of atherosclerosis and cardiovascular risk factors in patients with
      VTE and CTEPH. The purpose of the present study was to evaluate the arterial
      stiffening assessed by pulse wave velocity (PWV), a marker of arterial stiffness,
      in CTEPH patients in comparison with a matched control group (CG). METHODS: The
      study group consisted of 26 CTEPH patients (9 male and 17 female, age 69 +/- 10
      years) and 22 CG (10 male, 12 female, age 67 +/- 8 years). In all subjects a
      physical examination, carotid-femoral PWV and transthoracic echocardiography
      (TTE) were performed. Right heart catheterization was done in all CTEPH. RESULTS:
      CTEPH patients had significantly higher PWV than CG (10.3 +/- 2.5 m/s vs. 9 +/-
      1.3 m/s, p < 0.05), even though systolic blood pressure was higher in CG (120 +/-
      11 vs. 132 +/- 14 mmHg, p = 0.002). PWV correlated only with age and pulmonary
      vascular resistance (PVR) in CTEPH (r = 0.45, p = 0.03 and r = 0.43, p = 0.03,
      respectively). Arterial stiffening defined as PWV > 10 m/s was found in 11 (42%)
      CTEPH patients and in 5 (23%) cases from CG (p = 0.13). CTEPH patients with PWV >
      10 m/s were older (74 +/- 8 vs. 66 +/- 10 years, p < 0.05), had decreased oxygen
      saturation (SaO2 89 [73-96]% vs. 96 [85-98]%, p < 0.01) and tended to have higher
      PVR (8.1 [3.1-14.0] vs. 5.2 [3.1-12.7] HRU, p = 0.10). CONCLUSIONS: Arterial
      stiffness, assessed with PWV, is increased in CTEPH. The elevated PWV is
      associated with older age, lower SaO2 and higher PVR in CTEPH.

PMID- 30234893
TI  - The usefulness of selected biomarkers in aortic regurgitation.
AB  - BACKGROUND: The aim of the study was to investigate the prognostic value of
      selected biomarkers in patients with aortic regurgitation undergoing valve
      surgery. M: ETHODS: A prospective study was conducted on a group of consecutive
      patients with hemodynamically significant aortic regurgitation that underwent
      elective aortic valve surgery. The primary endpoint was 30-day mortality and any
      major adverse event within 30 days. RESULTS: The study group included 205
      consecutive patients who underwent replacement or repair of the aortic valve. The
      primary endpoint occurred in 72 patients. At multivariate analysis red cell
      distribution width (RDW) (p = 0.03) and high-sensitivity troponin T (hs-TnT) (p =
      0.02) remained independent predictors of the major complications including death.
      CONCLUSIONS: Elevated preoperative RDW and hs-TnT were associated with a poorer
      outcome following aortic valve surgery.

PMID- 30234894
TI  - Predictors of syncope in patients with severe aortic stenosis: The role of
      orthostatic unload test.
AB  - BACKGROUND: There is a paucity of data regarding response of cerebral blood flow
      to the postural unloading maneuver and its impact on the risk of syncope in
      patients with aortic stenosis (AS). The aim of the present study was to assess
      effects of orthostatic stress test on changes in carotid and vertebral artery
      blood flow and its association with syncope in patients with severe AS. METHODS:
      108 patients were enrolled (72 with and 36 patients without syncope) with severe
      isolated severe AS. Peak systolic blood-flow velocity (PSV) and end-diastolic
      velocity in the carotid arteries and vertebral arteries were measured by duplex
      ultrasound in the supine position and at 1-2 min after the assumption of the
      standing position. RESULTS: The orthostatic stress test induced a significant
      decrease in carotid and vertebral arterial flow velocities in all examined
      arteries (p < 0.001). The median (interquartile range) of mean change in PSV for
      carotid arteries was higher for patients with syncope (syncope [-] vs. syncope
      [+]: -0.6 cm/s [-1.8, 1.0] vs. -7.3 cm/s [-9.5, -2.0]; p < 0.001) and similarly
      for vertebral arteries: (-0.5 cm/s [-2.0, 0.5] vs. -4.8 cm/s [-6.5, -1.3]; p <
      0.001, respectively). Age, aortic valve area, and mean change in PSV for carotid
      arteries were independently associated with syncope. CONCLUSIONS: In patients
      with AS, a decrease in carotid and vertebral arterial flow velocities in the
      standing position was observed and was associated with syncope. The present
      findings may support the value of an orthostatic test in identifying patients
      with severe AS and a high risk of syncope.

PMID- 30234895
TI  - Lipoprotein(a) screening in young and middle-aged patients presenting with acute
      coronary syndrome.
AB  - BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for
      coronary artery disease (CAD). However, its role in real-world practice and
      implications for clinical care remains limited. Under investigation herein, are
      the clinical characteristics associated with increased Lp(a) levels in patients
      presenting with acute coronary syndrome (ACS). METHODS: Lp(a) was measured at
      admission in patients <= 65 years of age presenting with ACS in a single center.
      Logistic regression model was used to determine the independent association of
      clinical characteristics with elevated Lp(a). RESULTS: A total of 134 patients
      were screened for Lp(a); 83% males, mean age 52 +/- 8 years. Median Lp(a) level
      was 46 nmol/L (IQR 13-91). Elevated Lp(a) > 72 nmol/L (30 mg/dL) was documented
      in 32% and associated with younger age at CAD diagnosis. In a multiple logistic
      regression model, premature CAD (odds ratio [OR] 3.85, 95% confidence interval
      [CI] 1.48-10.07, p = 0.06), previous revascularization (OR 2.56, 95% CI 1.17
      5.59, p = 0.019) and probable/definite familial hypercholesterolemia (FH) (OR
      3.18, 95% CI 1.10-9.21, p = 0.033), were independently associated with elevated
      Lp(a). In contrast, Lp(a) levels were not associated with other traditional
      cardiovascular risk factors, previous statin treatment, C-reactive protein level
      or ACS type. CONCLUSIONS: In young and middle-aged patients presenting with ACS,
      premature CAD, previous revascularization and FH were independently associated
      with elevated Lp(a), indicating progressive CAD and higher cardiovascular risk.
      These results, are in accordance with guideline based recommendations for Lp(a)
      screening, and may be of importance in addressing residual cardiovascular risk in
      young ACS patients, in light of the novel emerging therapies targeting Lp(a).

PMID- 30234896
TI  - Reproducibility of quantitative flow ratio: An inter-core laboratory variability
      study.
AB  - BACKGROUND: Quantitative flow ratio (QFR) is a novel approach to derive
      fractional flow reserve (FFR) from coronary angiography. This study sought to
      evaluate the reproducibility of QFR when analyzed in independent core
      laboratories. METHODS: All interrogated vessels in the FAVOR II China Study were
      separately analyzed using the AngioPlus system (Pulse medical imaging technology,
      Shanghai) by two independent core laboratories, following the same standard
      operation procedures. The analysts were blinded to the FFR values and online QFR
      values. For each interrogated vessel, two identical angiographic image runs were
      used by two core laboratories for QFR computation. In both core laboratories QFR
      was successfully obtained in 330 of 332 vessels, in which FFR was available in
      328 vessels. Thus, 328 vessels ended in the present statistical analysis.
      RESULTS: The mean difference in contrast-flow QFR between the two core
      laboratories was 0.004 +/- 0.03 (p = 0.040), which was slightly smaller than that
      between the online analysis and the two core laboratories (0.01 +/- 0.05, p <
      0.001 and 0.01 +/- 0.05, p = 0.038). The mean difference of QFR with respect to
      FFR were comparable between the two core laboratories (0.002 +/- 0.06, p = 0.609,
      and 0.002 +/- 0.06, p = 0.531). Receiver operating characteristic curve analysis
      showed that diagnostic accuracies of QFR analyzed by the two core laboratories
      were both excellent (area under the curve: 0.970 vs. 0.963, p = 0.142), when
      using FFR as the reference standard. CONCLUSIONS: The present study showed good
      inter-core laboratory reproducibility of QFR in assessing functionally
      significant stenosis. It suggests that QFR analyses can be carried out in
      different core laboratories if, and only if, highly standardized conditions are
      maintained.

PMID- 30234897
TI  - Greater palatine foramen: assesment with palatal index, shape, number and gender.
AB  - Accurate knowledge of location and relation with different parameters of the
      greater palatine foramen (GPF) is a crucial necessity in performing a variety of
      anaesthesiological, dental and surgical procedures. The main aim of this study
      was to identify the GPF's locations, numbers and shapes via associating with
      gender and palatal indices and compare with literature results. This study was
      held on the cranium collections of the many anatomy departments in Turkey.
      Various metric assestments were observed on sexed, dry, total 97 craniums. Thirty
      eight male cranium observed and mean values of palatal indices was 86.28+/-10.75
      and for 48 female cranium mean value for palatal indices was 81.06+/-10.56.
      Location of GPF observed bilaterally and mostly found near the third upper molar
      in either of both males and females. It was 62.7% (right), 60.9% (left) for male
      craniums and 49.0% (right) and 47.1% (left) for female craniums observed near the
      lateral border of upper 3rd molar. GPF found oval shape for male craniums 62.8%
      (right) and 61.0% (left) and for female craniums 66.0% (right) and 66.0% (left).
      These results were compared with to already existing anatomical data in other
      races and populations. This results would have great clinical influence in
      localizing the palatine foramina toward better palatal area surgical approaches
      to and anaesthetise this area.

PMID- 30234898
TI  - Investigation of the styloid process length in a Greek population.
AB  - The styloid process (SP) is a slender cylindrical bony projection of the temporal
      bone with two ligaments and three muscles attached to it. Symptomatic SP
      elongation is also referred to, as Eagle's Syndrome. The aim of the present study
      is to investigate the distribution of the SP length in a young adult Greek
      population. Moreover we provide a comparison of the results by using two
      different methods for assessing SP elongation, as described in the literature.
      Finally we explore the possibility of using OPGs, as a diagnostic aid by
      investigating inter-examiner, intra-examiner and inter-examination variability
      and we propose a limit for SP elongation measurable in orthopantomograms (OPGs).
      The sample comprised of 805 digital OPGs, taken from student pilots and engineers
      entering the Hellenic Air Force Academy, from 2008 onwards.Two measuring
      approaches were selected, one using the temporal bone, as a cranial landmark and
      the other,the external auditory meatus. The end tip of the process was always the
      caudal landmark. The mean SP length was 28.42+/-8.48 mm in males and 26.04+/-7.69
      mm in females, when measured from the temporal bone. The mean SP length was
      38.35+/-8.90 mm in males and 34.24+/-8.63 mm in females, when measured from the
      external auditory meatus.The length of 30 mm is most commonly used as a starting
      point for SP elongation. In the total sample, 30.6% of the measured SPs exceeded
      the length of 30mm. In males, 33.12% of the SPs were elongated; while in females
      the corresponding incidence was 20%. An amount of 119 SPs (14.8%) were not
      traceable. The SP is typically detectable and measurable in OPGs. An elongated SP
      should be kept in mind, since symptoms of elongation may overlap with clinical
      manifestations of temporomandibular joint disorders.

PMID- 30234899
TI  - Cardiac sarcoidosis and ventricular arrhythmias. A rare association of a rare
      disease. A retrospective cohort study from the National Inpatient Sample and
      current evidence for management.
AB  - BACKGROUND: Sarcoidosis is an increasingly recognized multi-systemic condition.
      Cardiac sarcoidosis is associated with ventricular arrhythmias and higher
      mortality rates. Little epidemiological data is available regarding the disease
      and associated ventricular arrhythmias. METHODS: Data from the National Inpatient
      Sample (NIS) database 2012-2014, were reviewed. Discharges associated with
      sarcoidosis were identified as the target population using relevant ICD-9-CM
      codes. Primary outcome was a diagnosis of ventricular tachycardia (VT) in the
      sarcoidosis population. Secondary outcomes include rate of ventricular
      fibrillation (VF) and cardiac arrest. Subgroup analyses were performed to examine
      the association of VT with multiple potential confounding clinical variables.
      RESULTS: Of 18,013,878 health encounters, 46,289 (0.26%) subjects had a diagnosis
      of sarcoidosis. VT and VF were more prevalent among patients with sarcoidosis
      compared to those without a diagnosis of sarcoidosis (2.29% vs. 1.22%; p < 0.001
      and 0.25% vs. 0.21%; p < 0.001, respectively). Sarcoidosis was also associated
      with a higher prevalence of cardiac arrest (0.72% vs. 0.6%; p < 0.001). In
      unadjusted analyses, all examined comorbidities were significantly more common in
      those with sarcoidosis, including diabetes mellitus (31.6% vs. 21.25%; p <
      0.001), hypertension (65.2% vs. 51.74%; p < 0.001), chronic kidney disease
      (21.09% vs. 14.02%; p < 0.001), heart failure (24.87% vs. 15%; p < 0.001) and
      acute coronary syndrome (ACS) (4.32% vs. 3.35%; p < 0.001). CONCLUSIONS: The
      present study showed that sarcoidosis was associated with increased rates of
      ventricular tachyarrhythmia, which can affect the overall disease morbidity and
      mortality.

PMID- 30234900
TI  - Prognostic significance of red cell distribution width and its relation to
      increased pulmonary pressure and inflammation in acute heart failure.
AB  - BACKGROUND: Red cell distribution width (RDW) in acute heart failure (AHF) is
      accepted as a prognostic indicator with unclear pathophysiological ties. The aim
      of this study was to evaluate the prognostic value of RDW in AHF patients in
      relation to clinical and echocardiographic data. METHODS: 170 patients with AHF
      were retrospectively studied. All patients had laboratory testing and an
      echocardiogram performed within 24 h of admission to the Cardiology Department.
      RESULTS: During the mean 193 +/- 111 days of follow-up, 33 patients died. More
      advanced age, high RDW and low peak early diastolic velocity of the lateral
      mitral annulus (MVe') were independent predictors of all-cause mortality with
      hazard ratios of: 1.05 (95% CI 1.02-1.09), p < 0.005, 1.40 (95% CI 1.22-1.60), p
      < 0.001, and 0.77 (95% CI 0.63-0.93), p < 0.007 respectively. In a stepwise
      multiple linear regression model, RDW was correlated with hemoglobin
      concentration (standardized beta = -0.233, p < 0.001), mean corpuscular volume
      (MCV) (standardized beta = -0.230, p < 0.001), mean corpuscular hemoglobin
      concentration (MCHC) (standardized beta = -0.207, p < 0.007), the natural
      logarithm of C-reactive protein (LnCRP) (standardized beta = 0.184, p < 0.004)
      and tricuspid regurgitation peak gradient (TRPG) values (standardized beta =
      0.179, p < 0.006), whereas MVe' was correlated with atrial fibrillation
      (standardized beta = 0.269, p < 0.001). CONCLUSIONS: The present data
      demonstrates a novel relation between higher levels of RDW and elevated TRPG and
      hsCRP values in patients with AHF. These findings suggest that RDW, the most
      important mortality predictor, is independently associated with elevated
      pulmonary pressure and systemic inflammation in patients with AHF. Moreover, in
      AHF patients, more advanced age and decreased MVe' are also independently
      associated with total mortality risk.

PMID- 30234901
TI  - Diabetes and periprocedural outcomes in patients treated with rotablation during
      percutaneous coronary interventions.
AB  - BACKGROUND: This study is to assess differences in periprocedural outcomes among
      diabetic and non-diabetic patients treated with percutaneous coronary
      intervention (PCI) and rotational atherectomy (RA). METHODS: Under assessment
      were 221,187 patients from the Polish Cardiovascular Intervention Society
      national registry (ORPKI) including all PCIs performed in Poland in 2015 and
      2016. Data was extracted of 975 patients treated with RA - 336 (34.5%) diabetics
      and 639 (65.5%) non-diabetics. Periprocedural complications were defined as
      overall rate or particular complications such as deaths, no-reflows,
      perforations, dissections, cerebral strokes or bleedings.. Multivariate analysis
      was performed to assess predictors of periprocedural complications. RESULTS: The
      mean age was similar in diabetics and non-diabetics (70.9 +/- 9.0 vs. 72.1 +/-
      9.9; p = 0.06). Diabetics were more often females (p < 0.01), with arterial
      hypertension (p < 0.01), kidney failure (p < 0.01) and prior myocardial
      infarction (p = 0.01). No significant differences were observed in overall or
      individual periprocedural complications and angiographic success was expressed as
      thrombolysis in myocardial infarction grade 3 flow after PCI. At baseline, de
      novo lesions accounted for 96.5% in diabetics and 99% in non-diabetics (p <
      0.01), while overall rate of restenosis was 3.5% and 1%, respectively (p < 0.01).
      Diabetes was an independent predictor of periprocedural complications in the
      overall group of patients treated with PCI (OR 1.11, 95% CI 1.04-1.194; p <
      0.001). CONCLUSIONS: The negative impact of diabetes on the incidence of
      periprocedural complications and angiographic effectiveness in the group of
      patients treated with RA is mitigated in the comparison to the non-RA group.

PMID- 30234902
TI  - Coexistence and management of abdominal aortic aneurysm and coronary artery
      disease.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) and coronary atherosclerosis share
      common risk factors. In this study, a single-center management experience of
      patients with a coexistence of AAA and coronary artery disease (CAD) is
      presented. METHODS: 271 consecutive patients who underwent elective AAA repair
      were reviewed. Coronary imaging in 118 patients was considered suitable for
      exploration of AAA coexistence with CAD. RESULTS: Significant coronary stenosis
      (> 70%) were found in 65.3% of patients. History of cardiac revascularization was
      present in 26.3% of patients, myocardial infarction (MI) in 31.4%, and 39.8% had
      both. In a subgroup analysis, prior history of percutaneous coronary intervention
      (PCI) (OR = 6.9, 95% CI 2.6-18.2, p < 0.001) and patients' age (OR = 1.1, 95% CI
      1.0-1.2, p = 0.007) were independent predictors of significant coronary stenosis.
      Only 52.0% (40/77) of patients with significant coronary stenosis underwent
      immediate coronary revascularization prior to aneurysm repair: PCI in 32 cases (4
      drug-eluting and 27 bare metal stents), coronary artery bypass graft in 8 cases.
      Patients undergoing revascularization prior to surgery had longer mean time from
      coronary imaging to AAA repair (123.6 vs. 58.1 days, p < 0.001). Patients
      undergoing coronary artery evaluation prior to AAA repair had shorter median
      hospitalization (7 [2-70] vs. 7 [3-181] days, p = 0.007) and intensive care unit
      stay (1 [0-9] vs. 1 [0-70] days, p = 0.014) and also had a lower rate of major
      adverse cardiovascular events or multiple organ failure (0 vs. 3.9%, p = 0.035).
      A total of 11.0% of patients had coronary artery aneurysms. CONCLUSION: Patients
      with AAA might benefit from an early coronary artery evaluation strategy.

PMID- 30234903
TI  - Excessive left ventricular hypertrophy in moderate degenerative aortic stenosis:
      an ineffective compensatory mechanism triggered by primary myocardial dysfunction
      and enhanced by concomitant mild renal impairment?

PMID- 30234904
TI  - Long-term lipoprotein apheresis in the treatment of severe familial
      hypercholesterolemia refractory to high intensity statin therapy: Three year
      experience at a lipoprotein apheresis centre.
AB  - BACKGROUND: Severe familial hypercholesterolemia (FH) individuals, refractory to
      conventional lipid-lowering medications are at exceptionally high risk of
      cardiovascular events. The established therapeutic option of last choice is
      lipoprotein apheresis (LA). Herein, it was sought to investigate the clinical
      usefulness of LA in a highly selected group of severe heterozygous FH (HeFH), as
      recently described by the International Atherosclerosis Society (IAS), for their
      efficacy in lipid reduction and safety. METHODS: Efficacy and safety of LA were
      investigated in 318 sessions of seven severe HeFH females with cardiovascular
      disease, over a mean period of 26.9 +/- 6.5 months. Relative reduction of low
      density lipoprotein cholesterol (LDL-C) >= 60%, clinical complications and
      vascular access problems were evaluated and compared between the direct
      adsorption of lipoproteins (DALI) and lipoprotein filtration (Membrane Filtration
      Optimized Novel Extracorporeal Treatment [MONET]). Additionally, lipoprotein (a)
      [Lp(a)], total cholesterol (TC), high density lipoprotein cholesterol (HDL-C),
      triglycerides (TG) and fibrinogen concentrations were investigated. RESULTS: The
      relative reduction of LDL-C, TC, TG and Lp(a) were 69.4 +/- 12.9%, 59.7 +/- 9.1,
      51.5 +/- 14.2% and 71.3 +/- 14.4%, respectively. A similar efficacy was found in
      both systems in LDL-C removal. DALI system led to larger depletions of Lp(a)
      (80.0 [76-83]% vs. 73.0 [64.7-78.8]%; p < 0.001). The frequency of clinical side
      effects and vascular access problems were low (8.5%). CONCLUSIONS: Long-term LA
      in severe HeFH individuals is safe and efficiently reduces LDL-C and Lp(a).
      Higher efficacy of the DALI system than MONET in Lp(a) removal may indicate the
      need for individualized application of the LA system in severe HeFH individuals.

PMID- 30234905
TI  - Is downstream cardiac testing required in patients with reduced functional
      capacity and otherwise negative exercise stress test? A single centre
      observational study.
AB  - BACKGROUND: Exercise stress testing (EST) in patients with poor functional
      capacity measured by time on treadmill is typically deemed inconclusive and
      usually leads to further downstream testing. The aim of this study was firstly to
      evaluate the maximum rate pressure product (MRPP) during initial EST to assessthe
      need for follow-up testing; and secondly to investigate if MRPP is better than
      age predicted maximum heart rate (APMHR) for diagnostic outcome based on follow
      up cardiovascular (CV) events in patients with inconclusive EST due to poor
      functional capacity. METHODS: From a total of 2761 tests performed, 236 tests
      were considered inconclusive due to poor functional capacity which were available
      for analysis. From receiver operating characteristic (ROC) analysis, a cut-off
      value for MRPP of 25000 was chosen using CV events as the outcome measure
      (sensitivity 97%, specificity 45%). Cases were then categorised into those with
      an MRPP > 25000 and < 25000. RESULTS: Regardless of treadmill time, any patient
      attaining an MRPP > 25000 had no abnormal downstream testing or CV events at 2
      years follow-up. On ROC analysis MRPP outperformed APMHR for sensitivity and
      specificity (area under curve 0.76 vs. 0.59, respectively). CONCLUSIONS: The
      results suggest that regardless of functional capacity, individuals whose EST is
      terminated at maximal fatigue, with no electrocardiogram evidence or symptoms of
      myocardial ischemia and yields an MRPP > 25000, do not require further downstream
      testing. Furthermore, this group of patients, while not immune to future CV
      events, have significantly better outcomes than those not attaining a MRPP >
      25000.

PMID- 30234906
TI  - Sutureless aortic valve replacement in high risk patients neutralizes expected
      worse hospital outcome: A clinical and economic analysis.
AB  - BACKGROUND: Aortic valve replacement (AVR) by sutureless prostheses is changing
      surgeon options, although which patients benefit most, as well as their possible
      economic impact is still to be defined. METHODS: Perceval-S prosthesis (LivaNova)
      is reserved, at the documented Institution, for patients at perceived high
      surgical risk. This retrospective analysis of outcome and resource consumption
      compared Perceval with other tissue valves. To clarify the comparison, only
      patients respecting 'instructions-for-use' of Perceval were reviewed. INCLUSION
      CRITERIA: > 65 years, +/- coronary artery bypass grafting, PFO closure or
      myectomy. EXCLUSION CRITERIA: bicuspid, combined valve or aortic surgery. Costs
      were calculated per patient on a daily basis including preoperative tests,
      operating costs (hourly basis), disposables, drugs, blood components and
      personnel. RESULTS: The sutureless group (SU-AVR) had a higher risk profile than
      the sutured group (ST-AVR). Cardiopulmonary bypass (CPB) and cross-clamp times
      were significantly shorter in SU-AVR (isolated AVR: cross-clamp 52.9 +/- 12.6 vs.
      69 +/- 15.3 min, p < 0.001; CPB 79.4 +/- 20.3 vs. 92.7 +/- 18.2 min, p < 0.001).
      Hospital mortality was 0.9% in SU-AVR and nil in ST-AVR, p = 0.489; intubation 7
      (IQR 5-10.7) and 7 h (IQR 5-9), p = 0.785; intensive care unit 1 (IQR 1-1) and 1
      day (IQR 1-1), p = 0.258; ward stay 5.5 (IQR 4-7) and 5 days (IQR 4-6), p =
      0.002; pacemaker 5.7% (6/106) and 0.9% (1/109), p = 0.063, respectively. Hospital
      costs (excluding the prosthesis) were $12,825 (IQR 11,733-15,334) for SU-AVR and
      $12,386 (IQR 11,217-14,230) in ST-AVR, p = 0.055. CONCLUSIONS: Despite higher
      operative risks in SU-AVR, hospital mortality, morbidity and resource consumption
      did not differ. Operative times were shorter with the sutureless device and this
      improvement, along with more frequent ministernotomy, may have improved many
      postoperative aims.

PMID- 30234907
TI  - Association between mild thyroid dysfunction and clinical outcome in acute
      coronary syndrome undergoing percutaneous coronary intervention.
AB  - BACKGROUND: Thyroid hormones profoundly influence the cardiovascular system, but
      the effects of mild thyroid dysfunction on the clinical outcome of acute coronary
      syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) are
      not well defined. This study aimed to determine the effect of mild thyroid
      dysfunction on 12-month prognosis in ACS patients undergoing PCI. METHODS: In
      this prospective cohort study with a 12-month follow-up, 1560 individuals were
      divided into four groups based on thyroid hormone levels upon admission:
      euthyroidism (used as a reference group), subclinical hypothyroidism, subclinical
      hyperthyroidism, and low triiodothyronine syndrome (low T3 syndrome). The
      outcomes measured were all-cause mortality, cardiac mortality, nonfatal
      reinfarction, and unplanned repeat revascularization. RESULTS: In this study, the
      prevalence of mild thyroid dysfunction was 10.8%. Multivariate analysis showed
      that low T3 syndrome, but not subclinical hypothyroidism or subclinical
      hyperthyroidism, was associated with a higher rate of all-cause (HR 2.553, 95% CI
      1.093-5.964, p = 0.030) and cardiac mortality (HR 2.594, 95% CI 1.026-6.559, p =
      0.034), compared with the euthyroidism group. CONCLUSIONS: Mild thyroid
      dysfunction was frequent in patients with ACS undergoing PCI. Low T3 syndrome was
      the predominant feature and was associated with 12-month adverse outcomes in
      these patients.

PMID- 30234908
TI  - Assessment of community hospital disaster preparedness in New York State.
AB  - OBJECTIVE: The intent of this study was to assess disaster preparedness in
      community hospitals across New York. DESIGN: Descriptive and analytical cross
      sectional survey study. The survey instrument consisted of 35 questions that
      examined six elements of disaster preparedness: disaster plan development, onsite
      surge capacity, available materials and resources, disaster education and
      training, disaster preparedness funding levels, and perception of disaster
      preparedness. SETTING: Community hospitals in New York. SUBJECTS: Contact
      information was obtained for 207 of 208 community hospitals. Email invitations to
      participate in the survey were sent to hospital CEOs and disaster preparedness
      coordinators. Completed surveys were received from 80 hospitals. MAIN OUTCOME
      MEASURES: Hospital responses to questions related to the six elements of disaster
      preparedness. RESULTS: Most (87.5 percent) hospitals had experienced a disaster
      event during the past 5 years (2012-2016). Eighty percent had disaster plans that
      addressed all of six major types of disasters. Only 17.5 percent believed their
      disaster plans were "very sufficient" and did not require any revisions. Nearly
      three-quarters (73.3 percent) of hospitals could continue operations for less
      than a week without external resources. Less than half (49.4 percent) reported
      being satisfied or very satisfied with the level of funding that they received
      from the Hospital Preparedness Program. Most (88.8 percent) respondents felt that
      barriers to disaster preparedness exist for their organizations. CONCLUSIONS: The
      results demonstrate the current level of disaster preparedness among New York
      hospitals. The study's approach is discussed as a model that will enable
      hospitals to identify focus areas for improvement and opportunities for
      legislation and advocacy.

PMID- 30234909
TI  - Background to the four stages of emergency management: The role of enterprise
      GIS.
AB  - Few examples of enterprise geographic information systems (GISs) implementation
      are as important and illustrative as the use of GIS to support the four stages of
      emergency management (EM). The full range of data required to support the four
      stages of EM are much greater, then any one department can be responsible for by
      itself. Only with an enterprise-wide GIS perspective can the full range of
      required data elements be made available to the emergency manager. Most
      critically, to keep these data sets accurate and up to date, the emergency
      manager must rely on other agencies and functions to keep all the data current.
      Without other assistance, the data requirements for the EM team will be quickly
      overwhelming. Waugh and Hy describe emergency events as either intentional
      (terrorism) or unintentional (weather/earthquake). The focus of this analysis is
      primarily on unintentional events, yet examples show that the four stages of EM
      are applicable with either type of event. Enterprise GIS has not been discussed
      much lately, but it is absolutely critical to solving the information needs of
      the contemporary emergency manager. Enterprise GIS means that many of the key
      data sets needed to support the four stages of EM are readily available, in a
      consistent manner and are always up to date. An enterprise perspective also means
      that GIS data are compatible with surrounding areas and GIS products are
      consistent with local, state, and federal information needs/requirements. The
      "common operating picture" we hear so much about in today's EM world. Most
      importantly, an enterprise GIS perspective means that all data and systems work
      together or can "talk" to each other. Easily sharing data by address or by parcel
      means that the information/knowledge content can grow quickly and ad-hoc data
      requirements or events can be handled quickly and reliably. GIS is no longer a
      system or even just an architecture-it literally is a way of thinking. It is so
      exciting to implement GIS capabilities only to see that they can be used in ways
      not originally intended or described. This is analogous to the EM problem of
      having data/maps collected for the last emergency and not the current one! This
      means that the GIS staff get involved and more fully understand the in-depth
      system requirements of each application/data set. By putting these requirements
      together, in an enterprise-wide perspective, we can begin to see how a school
      inventory needed for drug free zones (for the district attorney's office) is also
      useful as a possible shelter/feeding/inoculation site inventory for EM. A cell
      tower inventory for address assignments (for E-911/CAD) may also prove useful to
      the assessment professionals who see income potentials in silos, flag poles and
      steeples, often on tax-exempt properties like churches or municipal water tanks.
      A gasoline station inventory from Health's Weights and Measures is immediately
      applicable to EM's requirements for a better understanding of possible gasoline
      rationing actions/scenarios. Another way of looking at enterprise GIS and its
      support of EM would be to always think about the other stages of EM as this
      particular data/map or application is being collected, designed, or implemented.
      Perhaps just including another data element or two could support other later (or
      earlier) stages of EM? The GIS data can provide the continuity that EM needs to
      handle an incident through the four stages.

PMID- 30234910
TI  - Help we are sinking! Stories from Norwegian dispatch centers on decision-making
      in unfamiliar and ambiguous situations.
AB  - The aim of this exploratory case study was to examine whether sensemaking
      processes may influence decision-making of emergency call center dispatchers when
      dealing with maritime crises. This article focuses on sensemaking and decision
      making in an emergency services context using Norwegian operators as a case and
      reports on data collected from five focus-group interviews with emergency
      dispatchers at five different locations. Each focus group consisted of three
      dispatchers, representing the three main Norwegian emergency response dispatch
      centers: police, fire and rescue, and the Emergency Medical Communication Centre
      (AMK). The study's purpose was to see whether choices made when responding to
      maritime crisis calls are influenced by sensemaking processes, and whether these
      processes may have influenced the dispatcher's choice of which search and rescue
      resources to contact. The study found that the sensemaking processes that
      occurred prior to the decision-making might have been influenced by the
      dispatcher's past experiences, in particular, experiences from land-based
      operations. The findings also suggested that the emergency dispatchers made
      decisions based on intuitive sensemaking, as they were perceived pressed on time
      and experienced maritime crisis in a more transboundary nature than everyday land
      based emergencies. The effects of sensemaking processes and intuitive decision
      making shown in this study are of possible relevance to emergency services
      educators and managers outside a Norwegian framework.

PMID- 30234911
TI  - Use of Facebook for civilian-led disaster response after a winter storm: A
      "Snowed Out Atlanta" case study.
AB  - OBJECTIVE: To determine disaster response-related contexts and themes of Facebook
      posts that were communicated on the "Snowed Out Atlanta" Facebook page in
      response to winter storm Leon in 2014. DESIGN: A content analysis. PARTICIPANTS:
      A sample of 537 posts from the "Snowed Out Atlanta" Facebook page posted between
      January 29, 2014 and February 4, 2014. MAIN OUTCOME MEASURES: (1) Disaster
      response-related contexts and themes of Facebook posts communicated in response
      to winter storm Leon; (2) the shift in the contexts and themes of posts following
      the storm; and (3) health-related significance of posts for disaster epidemiology
      purposes. RESULTS: Of the 537 posts from the "Snowed Out Atlanta" Facebook page,
      260 posts (48 percent) were of importance to disaster response efforts. Thirty
      eight percent of these posts offered some form of assistance, of which general
      help and assisting with basic necessities were the dominant themes. One day after
      winter storm Leon, 189 (64 percent) of the Facebook posts were related to
      disaster response. Findings also show that very few posts (3.2 percent) from the
      "Snowed Out Atlanta" page were relevant for disaster epidemiology purposes.
      CONCLUSION: Overall, the "Snowed Out Atlanta" Facebook page is a representation
      of how social media forums can be used to mitigate adverse effects of severe
      winter weather events. Nearly half of the Facebook posts were relevant for
      disaster response and were more common in the immediate aftermath of winter storm
      Leon. Most of the posts offered general help or assistance with basic
      necessities. An analysis of posts with health-related content suggested that
      disaster epidemiology should be emphasized less for severe winter weather
      compared to other hazards. The results from this study provide insightful
      information to anticipate the needs of people adversely impacted by severe winter
      weather.

PMID- 30234912
TI  - Emergency preparedness: What do new college students need to know and how do you
      inform them?
AB  - Active shooters, tornadoes, fires, floods, and power outages are concerns for
      every new student entering college. New students enter college with a variety of
      academic and nonacademic anxieties. Students express concerns of their study
      skills, as well as their ability to manage financial and social responsibilities,
      but seldom does a new student worry about personal safety or disasters. The first
      few minutes of an emergency can mean the difference between life and death.
      Candlelight vigils showing incredible sorrow among college students may become
      more frequent as active shooter incidents continue to increase in frequency and
      will undoubtedly occur again. The question is: What do new students need to know
      about emergency preparedness and how do you inform them? Information overload
      combined with new student mindset of invincibility makes emergency preparedness a
      tough topic to communicate effectively to new students. University officials owe
      it to new students to try.

PMID- 30234913
TI  - Social media as a public alert and notification system.

PMID- 30234914
TI  - Planning considerations for persons with access and functional needs in a
      disaster-Part 1: Overview and legal.
AB  - Although disasters can affect anyone in a given community or region, those with
      access and functional needs have the highest rates of morbidity and mortality
      during an emergency or disaster. There are many unique and complex issues that
      should be considered when planning and caring for these individuals in a disaster
      situation. Who are these individuals, what specific issues should be addressed
      when considering these members of the population, and what recommendations can be
      made to address their unique needs? How can we include them as part of the all
      hazard, comprehensive approach to disaster management? The first part of this
      three-part series identifies who is included in this population and what are the
      legal considerations that arise in caring for, not only this unique group but
      also all the members of the community in a disaster. The second part considers
      evacuation, sheltering, sheltering in place, communication, medical needs,
      independence, supervision, and transportation (CMIST) with a focus on mental
      health. The third part deals with the medical aspect of CMIST and with
      recommendations that may aid disaster responders and planners in caring for these
      high-risk individuals in a disaster.

PMID- 30234915
TI  - Parents' awareness of disaster plans in children's early learning settings.
AB  - OBJECTIVE: Children in early learning settings are vulnerable to site-specific
      emergencies because of physical and developmental limitations. We examined
      parents' knowledge of disaster plans in their child's early learning settings.
      METHODS: In May 2015, we conducted a nationally representative online household
      survey, including parents of children ages 0-5 years in child care settings.
      Parents were asked about their center's disaster plans and key components:
      evacuation, special needs children, and disaster supplies. Bivariate analyses and
      logistic regression were conducted to identify factors associated with parental
      awareness of disaster plans. RESULTS: Overall, 1,413 of 2,550 parents responded
      (rate = 55 percent). Sample included 1,119 parents of children 0-5 years old,
      with 24 percent (n = 264) requiring child care. Parents' reported knowledge of
      five types of disaster plans: evacuation (66 percent), power outage (63 percent),
      severe weather (62 percent), lock-down (57 percent), and delayed parent pick-up
      (57 percent). Only 21 percent reported if plans included all four key components
      of evacuation (child identification, parent identification, rapid communication,
      and extra car seats). One-third (36 percent) reported plans accommodating special
      needs children. Parents' knowledge of disaster supplies varied: generator (31
      percent), radio (42 percent), water (57 percent), food (60 percent), and first
      aid (82 percent). Parents attending any disaster training events (34 percent)
      were more likely to be aware of all five types of disaster plans compared with
      parents who had not attended. CONCLUSIONS: Many parents were unaware of disaster
      plans at their children's early learning settings. Although few parents attended
      training events, such participation was associated with higher levels of parental
      awareness.

PMID- 30234916
TI  - Humerus intraosseous administration of epinephrine in normovolemic and
      hypovolemic porcine model.
AB  - OBJECTIVE: Compare the maximum concentration (Cmax), time to maximum
      concentration (Tmax), mean concentration, rate of return of spontaneous
      circulation (ROSC), time to ROSC, and odds of ROSC when epinephrine is
      administered by humerus intraosseous (HIO) compared to intravenous (IV) routes in
      both a hypovolemic and normovolemic cardiac arrest model. DESIGN: Prospective,
      between subjects, randomized experimental study. SETTING: TriService Facility.
      SUBJECTS: Twenty-eight adult Yorkshire Swine were randomly assigned to four
      groups: HIO normovolemia; HIO hypovolemia; IV normovolemia; and IV hypovolemia.
      INTERVENTION: Swine were anesthetized. The hypovolemic group was exsanguinated 31
      percent of their blood volume. Subjects were placed into arrest. After 2 minutes,
      cardiopulmonary resuscitation (CPR) was initiated. After another 2 minutes, 1 mg
      epinephrine was given by IV or HIO routes; blood samples were collected over 4
      minutes. Hypovolemic groups received 500 mL of 5 percent albumin following blood
      sampling. CPR continued until ROSC or for 30 minutes. MAIN OUTCOME MEASURES:
      ROSC, time to ROSC, Cmax, Tmax, mean concentrations over time, odds of ROSC.
      RESULTS: Cmax was significantly higher, the Tmax, and the time to ROSC were
      significantly faster in the HIO normovolemic compared to the HIO hypovolemic
      group (p < 0.05). All seven in the HIO normovolemic group achieved ROSC compared
      to three of the HIO hypovolemic group. Odds of ROSC were 19.2 times greater in
      the HIO normovolemic compared the HIO hypovolemic group. CONCLUSION: The HIO is
      an effective route in a normovolemic model. However, the findings indicate that
      sufficient blood volume is essential for ROSC in a hypovolemic scenario.

PMID- 30234917
TI  - A scoping review of evaluation methods for health emergency preparedness
      exercises.
AB  - OBJECTIVE: To review and analyze evaluation methods currently utilized in health
      emergency preparedness exercises (HEPE). DESIGN: This study, part of a larger
      scoping review that systematically collected and reviewed published evidence
      related to the benefits of HEPE, provides a further analysis of the evaluation
      methods utilized in such exercises. We separately analyzed discussion-based and
      operation-based exercises according to their purpose. This addresses a
      methodological limitation related to the poorly understood relationship between
      the purpose and context in which a specific evaluation method is selected to be
      used. RESULTS: In the reviewed 64 studies, a variety of evaluation methods were
      utilized for HEPE including observations, participants' survey, and post-exercise
      debriefs. At present, the selection and use of these methods is not guided by any
      methodology, but seems rather arbitrary. No specific evaluation methods were
      isolated for any exercise type. CONCLUSIONS: The purpose of evaluation should
      guide the selection of evaluation methods for HEPE, and these are not context
      specific. If evaluation is for accountability purposes, such as to test
      organizational capability to respond, participant feedback should be collected in
      addition to objective data on performance in an exercise. Advantages of routinely
      collecting data from exercise participants to study their reactions (exercise
      feedback, perceptions, satisfaction with the exercise) and routinely conducting
      post-exercise debriefs (both hot debrief and cold debrief), are discussed to
      support evaluation for development or learning purposes in any context.

PMID- 30234918
TI  - No one left behind: Postevent experiences of differently abled individuals in
      Denmark.
AB  - PURPOSE: This descriptive study explored barriers and difficulties faced by
      individuals with a physical disability (IPD) in Denmark in situations of disaster
      and in everyday problems. METHODS: Semistructured interviews were conducted with
      12 IPD who had experienced a possible traumatic event. Due to a lack of
      participants who experienced a traumatic event, the authors expanded their
      recruitment strategy to include IPD, who had experienced other critical
      situations (eg, accidents and personal crises). RESULTS: Difficulties centered on
      four major themes: (1) lack of guidelines and evacuation plans, (2) differences
      in reaction to crisis, (3) a lack of empathy and special care from professionals
      and a general lack of communication directly to the IPD, and (4) great inequality
      in the municipals and no consistent rules for what a IPD is entitled to.
      CONCLUSIONS: This study has identified significant gaps in predisaster and
      postdisaster service provision for IPD. There is a need for general evacuation
      guidelines and more specialized professional help to provide better aftercare
      according to the different needs of the IPD. The results of this study can inform
      policy makers to enhance existing services and/or develop new guidelines and
      evacuation plans targeted at this population.

PMID- 30234919
TI  - Are physicians fully aware of the potential transgenerational and
      multigenerational effects of a large opioid misuse in the population?

PMID- 30234920
TI  - Association between the North Carolina Medical Board opioid guideline update and
      opioid prescriptions in Medicare Part D beneficiaries.
AB  - OBJECTIVE: To examine if North Carolina (NC) opioid prescribing guidelines were
      associated with changes in opioid prescribing. METHOD: Retrospective secondary
      analysis of the Medicare Provider Utilization and Payment Data: Part D Prescriber
      datasets from 2013 to 2015. PARTICIPANTS: Providers who prescribed at least one
      opioid from 2013 to 2015 and paid by Medicare Part D. MAIN OUTCOME MEASURE: Per
      prescriber Medicare-population adjusted number of analgesic opioid claims and per
      prescriber average day supply. Generalized estimating equations (GEE) were used
      to analyze the data. RESULTS: There were significantly higher per-prescriber
      Medicare adjusted opioid claims in 2014 compared to 2015 (p < 0.001) but no
      difference between 2013 and 2015 (p = 0.584). GEE results also indicated that
      there was a significant increase in 2015 in per-prescriber average day supply,
      compared to 2013 and 2014 (both p < 0.0001). CONCLUSIONS: State opioid
      prescribing guidelines published in mid-2014 may have slowed the escalation of
      numbers of opioid prescriptions in NC. Future research should examine whether the
      guidelines were associated with changes in morphine equivalent dosing in NC
      during the same timeframe.

PMID- 30234921
TI  - Opioid analgesics prescription in people with and without cancer in France.
AB  - INTRODUCTION AND OBJECTIVES: According to World Health Organization
      recommendations, opioids prescription is a key aspect of improvement in cancer
      pain relief. However, studies on opioids prescription in France are scarce. This
      study aimed principally to investigate the impact of cancer on opioids
      prescription and then to identify factors associated with this prescription,
      focusing on patients& characteristics impact. METHODS: We matched the following
      two cohorts: cancer survivors (N = 6,760) and individuals without cancer (N =
      6,760). Using French health insurance databases, we compared the prevalence of
      prescribed opioids in 2009-2015 in people with and without cancer and we applied
      afterwards conditional Poisson regressions to estimate relative risks for monthly
      opioids prescription. For cancer survivors only (N = 3,055), multivariate
      negative binomial regressions were performed to identify factors associated with
      opioids prescription. RESULTS: Cancer was associated with a higher analgesics
      prescription in the cancer population. While Step II and III opioids prescription
      decreased over time, the latter remained marginal and tended to stabilize. Older
      people were most adversely affected by underprescription of opioids, especially
      Step III opioids. Furthermore, although the matched case/control study suggested
      that men were prescribed opioids more often than women, multivariate analysis did
      not support this finding. CONCLUSION: The inconsistency between our findings and
      existing literature regarding both opioids prescription trends and postdiagnosis
      pain chronicity in cancer survivors over the medium term suggests possible
      changes in pain perception and the evolution of cancer pain management
      strategies. Further research should explore these hypotheses and investigate
      patient characteristics& effect in cancer pain management.

PMID- 30234922
TI  - Impact of rescheduling hydrocodone-combination products in an urban Texas county
      healthcare system.
AB  - OBJECTIVE: The objective of this study was to examine the rescheduling of
      hydrocodone-combination products (HCPs) and associated changes in prescriber
      patterns in an urban county healthcare system in Texas. METHODS: Pharmacy data
      were obtained electronically for tramadol, hydrocodone-acetaminophen, and
      acetaminophen-codeine from 180 days before and after the schedule change on
      October 6, 2014. x2 and t tests were used to calculate the significance of
      changes between the medications over the studied time. RESULTS: Hydrocodone
      acetaminophen saw a decline in dispense events and pills dispensed of 80.2 and
      67.9 percent, respectively, in the immediate 30-day period following the
      scheduling change with a total decrease of 80.8 and 67.5 percent, respectively,
      in the 180-day period. Acetaminophen-codeine dispense events and total pills
      dispensed increased by 302.3 and 288.9 percent, respectively, in the immediate 30
      day period while 180-day results experienced an increase of 215.1 and 209.8
      percent, respectively. There were no major changes with tramadol. Additionally,
      an increase of 69.5 percent in pills per dispense event of hydroco-done
      acetaminophen was noted in the 180-day period following the schedule change.
      CONCLUSION: The scheduling change of HCPs is associated with an immediate
      decrease in hydrocodone-acetaminophen use at our institution while a simultaneous
      rise in acetaminophen-codeine products was observed.

PMID- 30234923
TI  - Trends in and predictors of hydromorphone administration in US emergency
      departments (2007-2014).
AB  - OBJECTIVE: To examine recent trends in and predictors of hydromorphone
      administration in US emergency departments (EDs) compared with other opioids.
      DESIGN: Retrospective review of data from the National Hospital Ambulatory
      Medical Care Survey from 2007 to 2014. PARTICIPANTS: All adult ED visits where an
      opioid analgesic was administered were included. MAIN OUTCOME MEASURES: Trends in
      and predictors of hydromorphone administration were assessed using survey
      weighted logistic regression, comparing hydromorphone visits with ED visits where
      other opioids were administered. RESULTS: From 2007 to 2014, in an estimated
      128.9 million US ED visits where opioids were administered, hydromorphone use
      increased significantly from 30.2 percent in 2007 to 36.8 percent of visits in
      2014 (p = 0.027). Hydromorphone accounted for a greater proportion of opioids
      administered by the end of the study period, compared to other opioids. Patient
      characteristics associated with hydromorphone were age <65 years, white race,
      private insurance or Medicare, and severe pain. Patients who received
      hydromorphone also had indicators of higher severity illness, including more
      laboratory testing, procedures, and higher admission rates. Common conditions
      where hydromorphone was administered were headache, back pain, musculoskeletal
      pain, and abdominal pain. CONCLUSION: From 2007 to 2014, hydromorphone was
      administered to more than one in three US ED patients who were administered
      opioids, and several factors predicted its use. High use was found in some
      conditions where opioid use is inappropriate, suggesting a need for additional
      initiatives to promote rational prescribing of high-potency opioids.

PMID- 30234924
TI  - Opioid use: Case-control analyses of worker's compensation data.
AB  - OBJECTIVES: Working-age adults are disproportionately impacted by opioid misuse.
      Factors associated with opioid misuse in people with workers compensation (WC)
      claims are not well studied. WC in some states is a "captured" market making it a
      more efficient site for researching the opioids epidemic. A pilot study was
      conducted to identify factors associated with opioid use using a large WC
      insurer's claims in Utah. METHODS: This was a case-control study using a large WC
      insurer's database. We conducted secondary data analyses of a de-identified
      dataset originally obtained from the WC insurer. Cases were defined as claims
      with a morphine equivalent dose (MED)>=50 mg/d in the 30 days after the claim was
      filed while controls = 0 mg/d. RESULTS: A total of 76 patient's claims (28 cases
      and 48 controls) were included in the final data analyses. The majority of
      claimants were male (N = 50, 65.8 percent), worked full time (N = 58, 76.3
      percent) and had a mean age of 37.0+/-11.4 years. The majority of controls filed
      medical only claims (N = 40, 83.3 percent) while the majority of cases filed
      indemnity claims (N = 19, 67.9 percent). Cases were prescribed a mean MED of
      126.4 (SD = 93.3) within the first month after filing the claim. Most cases
      visited>3 medical providers (N = 13, 46.4 percent) in the first month after
      filing the claim while the majority of controls only visited one provider (N =
      28, 58.3 percent). Remarkably, the mean number of providers visited within the
      first month for the cases was 3.8, which was 2-fold greater than the control
      group. Exploratory multivariate analyses showed that cases were 4.6 times more
      likely to have visited 2-3 medical providers (p = 0.025), and 41.8 times more
      likely to have visited more than three medical providers (p < 0.001). Cases had
      3.6 higher odds of having been prescribed nonsteroidal anti-inflammatory
      prescription within the first month as compared to controls (p = 0.014).
      CONCLUSION: This pilot study found risk factors, some of which may be modifiable.
      We aim to conduct a large study using existing WC data to create a scoring system
      that identifies those claimants at higher risk of adverse opioid-related events
      that may have preventive applications at a systems-level.

PMID- 30234925
TI  - The impact of preinduction fentanyl dosing strategy on postoperative nausea and
      vomiting in patients undergoing laparoscopic cholecystectomy.
AB  - OBJECTIVE: Postoperative nausea and vomiting (PONV) is commonly attributed to
      opioid analgesics; consequently, perioperative opioid dosage reduction is a
      common practice. However, inadequate fentanyl analgesia may have adverse
      implications (sympathetic activation, pain). We conducted this randomized
      clinical study to analyze whether preinduction fentanyl 3 ug kg-1 administered by
      different techniques increases incidence of PONV. DESIGN: Randomized-control,
      prospective, investigator and observer blinded, two-arm, single-center
      comparison. SETTING: Operating room, postoperative ward. PATIENTS: Two hundred
      seventy patients, aged 20-60 years of either sex and belonging to ASA physical
      status I/II, scheduled to undergo laparoscopic cholecystectomy under general
      anesthesia. INTERVENTIONS: The patients were randomly allocated to receive
      preinduction fentanyl 3 ug kg-1 administered by "single-bolus," three equally
      divided "intermittent boluses" or a "short-infusion" technique. MAIN OUTCOME
      MEASURES: The patients were evaluated for PONV profile (primary outcome); and
      postoperative parameters (pain, sedation, respiratory depression) (secondary
      outcome). RESULTS: Two hundred fifty-seven patients completed the study and 29.1
      percent (n = 75) experienced PONV. The study groups were comparable for PONV
      incidence ("single-bolus": n = 23, 25.8 percent; "intermittent-boluses": n = 27,
      32.5 percent; "short-infusion": n = 25, 29.4 percent), total frequency of PONV
      ("single-bolus": n = 28, 31.5 percent; "intermittent-boluses": n = 39, 47.0
      percent; "short-infusion": n = 36, 42.4 percent), and frequency of rescue
      antiemetic usage ("single-bolus": n = 24, 30.7 percent; "intermittent-boluses": n
      = 28, 35.8 percent; "short-infusion": n = 26, 33.3 percent). Patients who
      received preinduction fentanyl as "intermittent-boluses" were less sedated in the
      postoperative period (p < 0.001). CONCLUSIONS: Controlled administration of
      preinduction fentanyl 3 ug kg-1 by commonly employed administration methods does
      not seem to impact PONV profile. Further studies are needed to establish a
      temporal link between preinduction fentanyl and PONV.

PMID- 30234927
TI  - Dental Public Health in Action: Understanding oral health care needs and oral
      health-related quality of life in vulnerable adults in Plymouth.
AB  - This paper aims to provide a snapshot analysis of the oral health status of
      vulnerable adults in Plymouth; and to demonstrate the extent to which oral
      disease impacts on their normal functioning through the implementation of the
      Oral Health Impact Profile (OHIP). It is acknowledged that gaining a
      representative sample of a transient population such as people who are homeless,
      or individuals affected by problematic use of drugs and/or alcohol is difficult.
      An opportunity was identified to collect data within the Community Engagement
      Team's (CET) programme of activity within the Peninsula Dental Social Enterprise.
      The CET works alongside local organisations to enable dental students from
      Peninsula School of Dentistry to undertake outreach programmes in a variety of
      settings. A study was designed which aimed to analyse the oral health status of
      vulnerable adults accessing three day-support services in Plymouth, and to
      understand the extent to which oral disease impacts on their normal functioning
      through the OHIP-14. For all impact domains, the 44 patients in this study
      reported a greater impact than that found in the Adult Dental Health Survey. The
      most commonly reported impact domains were physical pain and psychological
      discomfort. The sample was divided into high and low oral health-related quality
      of life impact groups, and those participants in the high impact group had
      significantly greater median D3MFT scores, i.e. higher levels of decay
      experience. This survey highlights how these vulnerable groups are characterised
      by a high prevalence of poor oral health, ill-health, deprivation and social
      exclusion.

PMID- 30234926
TI  - Provider reasons for discontinuing long-term opioid therapy following aberrant
      urine drug tests differ based on the type of substance identified.
AB  - OBJECTIVE: Urine drug testing (UDT) is increasingly performed as a means of
      identifying aberrant behavior that may be grounds for discontinuation of long
      term opioid therapy (LTOT). Little is known, however, about the ways in which
      positive UDT results may differentially inform decisions to discontinue LTOT
      based on the type of substance for which the UDT screened positive. The aim of
      this study was to examine the likelihood of clinician-initiated discontinuation
      of LTOT attributed to positive UDT results across three discrete categories of
      substances: (1) cannabis, (2) alcohol or illicit substances (excluding cannabis),
      and (3) controlled prescription medications that were not prescribed. DESIGN:
      This retrospective study utilized the US Department of Veterans Affairs (VA)
      Health Care System. Corporate Data Warehouse to assemble a sample of 600 patients
      with substance use disorders and matched controls who were discontinued from LTOT
      in 2012. Comprehensive manual medical record review identified UDT results in the
      year prior to discontinuation and reason(s) for discontinuation. PATIENTS,
      PARTICIPANTS: Patients with one or more UDTs positive for a single substance (N =
      185) comprised the study sample. MAIN OUTCOME MEASURE(S): Likelihood of clinician
      initiated discontinuation attributed to a positive UDT across the three
      categories. RESULTS: Patients with one or more UDTs positive for cannabis were
      more likely to be discontinued from opioid therapy as a result of the positive
      UDT compared to those with one or more UDTs positive for nonprescribed
      prescription medication (adjusted odds ratio [OR] = 18.05, 95% CI = 7.29-44.66).
      Similarly, patients with UDTs positive for alcohol or illicit substances were
      more likely to be discontinued for the positive UDTs relative to patients who
      tested positive for nonprescribed prescription medications (adjusted OR = 13.10,
      95% CI = 4.81-35.68). No difference in UDT-related discontinuation decisions was
      evident between patients with UDTs positive for alcohol/illicit substances versus
      cannabis (adjusted OR = 1.47, 95% CI = 0.57-3.77). CONCLUSIONS: High odds of UDT
      related discontinuation were found in patients who tested positive for cannabis,
      alcohol, or illicit substances, relative to nonprescribed prescription
      medications.

PMID- 30234942
TI  - [Analysis of Theory and Performance of Multi Layer Graphene Nanoribbons
      Photodetector].
AB  - Multilayer graphene, with wide absorption spectrum and unique photoelectric
      properties, is an ideal material to make the next generation of photoelectric
      detector. Taking graphene interband tunneling theory as the foundation, a
      photoelectric detector model with the structure of multilayer graphene
      nanoribbons was proposed. Nanoribbons which contacted with source and drain
      electrode at the end were sandwiched between the semiconductor substrate and the
      top and back gate. Using this model, a photoelectric conversion mechanism of
      multilayer graphene nanoribbon detector was established. It discussed the working
      principle of the detector at different top gate voltage, studied the relationship
      between the source-drain current and the incident light energy, researched the
      influence of the bias voltage, the length of depletion and the values of band gap
      on the dark current, and analyzed the change of detector responsibility and
      detectivity with the incident light energy under the different parameters. The
      results show that, the responsibility of detector increases with the layers of
      nanoribbons, and are affected by the band gap, the length of depletion and the
      bias voltage. The maximum responsibility up to 10(3) A.W(-1); By limiting on the
      top gate voltage, the band gap and other variables can control the dark current
      of system and increase the detectivity, the detectivity up to a maximum value of
      10(9) cm Hz(1/2).W(-1). The structure of multilayer graphene nanoribbons can
      enhance the absorption of the incident light, improve the sensitivity of the
      detector and the detection capability of weak light, and realize the detection
      from THz to far infrared wavelength of incident light. The detection performance
      is far better than that of many quantum structures and narrow-band semiconductor
      structure of photoelectric detector.

PMID- 30234943
TI  - [Haze Spectral Analysis and Detection Algorithm Using Satellite Remote Sensing
      Data].
AB  - Frequent occurring of haze pollution events and high fine particulate matter
      (PM(2.5)) concentration in China have attracted more and more attention in the
      world. Satellite remote sensing can be used to characterize the air pollution.
      However, haze is usually misidentified as fog, thin cloud or bright surface in
      NASA's Moderate Resolution Imaging Spectrometer (MODIS) cloud and clear days'
      aerosol products, and the retrieval of its optical properties is not included in
      MODIS cloud detection and dark target algorithm. This approach first studies the
      spectral characters of cloud, fog, haze, and land cover pixels. Second, following
      the previous cloud detection and aerosol retrieval literatures, a threshold
      algorithm is developed to distinguish haze from other pixels based on MODIS multi
      band apparent reflectance and brightness temperature. This algorithm is used to
      detect the haze distribution over North China Plain in 2008 spring and summer.
      Our result shows a good agreement with the true-color satellite images, which
      enhances MODIS's ability to monitor the severe air pollution episodes. In
      addition, the high AOD data from Beijing and Xiang Aerosol Robotic NETwork
      (AERONET) sites indicate nearly 80% haze days are detected by our approach.
      Finally, we analyze the errors and uncertainties in haze detection algorithm, and
      put forward the potential improvements.

PMID- 30234944
TI  - Multimodality imaging of gastric glomus tumor presenting with upper GI bleed.

PMID- 30234945
TI  - [Research Progress of Far Field Light Scattering Spectra of Single Gold
      Nanorods].
AB  - The far-field optical technology of single gold-nanorod(AuNR) has attracted a
      great deal of attention in recent years. Because of special local surface plasmon
      resonance (LSPR) property, AuNR particles have high conductivity of optical
      signals localized on the surface from physical or chemical irritants. The
      mechanism, application, progress and novel optical characteristics of AuNRs in
      optical detection and spectroscopy method are being reviewed in our work. The
      paper describes an overall introduction as follows: (1)various related
      technologies on AuNR scattered spectrum, including dark-field technology,
      homodyne and heterodyne technology, photonic crystal technology, spatial
      modulation, polarization modulation technology, etc; (2) the properties of AuNR
      scattered spectrum, including spectral line-shape functions, effects of line
      width and substrate, comparison of theoretical and experimental spectrums, etc;
      (3) the development of related spectrum technologies in recent years. The paper
      focuses on the method of far-field optical scattering based on LSPR and mainly
      discusses the linear method based on AuNRs, such as direct and indirect
      scattering detection method. We also put emphasis upon studying the importance of
      medium environment (for example, substrate, the molecules combined on surface and
      other nanomaterials) and the influence on scattered spectrum and the extinction
      rate. Of particular note is the quantitative method and correlation studies of
      AuNR's surface and morphology, and its character is that most of the methods are
      compared with theoretical model and experiments in terms of accuracy. The
      combination of the experiments and theoretical tools can be used to explain the
      optical properties of single gold-nanorod particle in detail.

PMID- 30234946
TI  - Stapler hepatectomy in giant cavernous hemangioma of liver.

PMID- 30234947
TI  - Spontaneous perforation of an ileal J pouch.

PMID- 30234948
TI  - AMA-negative primary biliary cirrhosis in a young male.

PMID- 30234949
TI  - [Simulation of Concentration Measurement of SO(2), NO(2) and Particles
      Simultaneously by Differential Optical Absorption Spectroscopy].
AB  - Our daily life is disturbed seriously by the haze weather now. It is very
      important to measure the haze composition quantificationally. The main
      composition of haze is SO(2), NO(2) and particles. At present, the research of
      measuring gas and particle simultaneously is rare relatively. This paper use
      differential optical absorption spectroscopy (DOAS) to simulate the concentration
      measurement of gas and particle simultaneously and obtain some meaningful
      results. Absorption spectral of many groups of different concentration of SO(2),
      NO(2) and particle were simulated, and each concentration was inverted by DOAS.
      In the first group of single component, the concentration change from 100 to 1
      000 ppm, the inverted error of SO(2) is not greater than 0.17%, and which is
      0.64% for NO(2). When the diameter of particle change from 100 to 500 nm, the
      inverted error is not greater than 2.08%. In the second group of multiple gases,
      when the concentration ratio of SO(2) and NO(2) is at the range of 1 : 10 and 5 :
      1, the error of SO(2) is not bigger than 8%, and 5% for NO(2), relatively. But
      when the concentration of SO(2) is 10 times than NO(2), the error is higher than
      10% for NO(2). In the third group of gas and particle, the error of gas
      concentration is lower than 10%, but the concentration error of particle is
      depended on signal to noise ratio (SNR) greatly. When SNR is higher than 40 dB,
      error can lower than 10% and when SNR is lower than 30dB, the error is bigger
      than 20%. From these results, we can see that DOAS can measurement SO(2), NO(2)
      and particles simultaneously effectively, and can applied to measure and analyze
      haze composition. However, when the absorption strength of the gases is different
      greatly, the strong absorption gas influent the weak absorption gas largely. And
      the SNR is lower, the error of inverted particle concentration increased greatly.
      The solution of these problems need better filtering and noise reduction method.

PMID- 30234950
TI  - Esophageal mucocele after surgical isolation of thoracic esophagus presenting
      with respiratory distress.

PMID- 30234951
TI  - ALPPS for a large hepatocellular carcinoma in hepatitis C patient.

PMID- 30234952
TI  - [Tissue Intrinsic Fluorescence Spectrum Recovering Based on Diffusion Theory].
AB  - Tissue intrinsic fluorescence spectrum refers to the fluorescence that is not
      impaired by tissue absorption and scattering which has the ability to reflect
      tissue biochemical properties. In order to reduce the influence of tissue
      absorption and scattering properties on tissue fluorescence spectrum, and then
      recover tissue intrinsic fluorescence spectrum, a tissue spectrum detection
      system based on fiber-optic probe was developed for the measurement of tissue
      fluorescence spectrum and diffusion reflectance spectrum at the same place. On
      the other hand, diffusion theory was introduced to extract the tissue
      physiological parameters from the measurement tissue diffusion reflectance
      spectrum, which included blood volume fraction, oxyhemoglobin saturation, melanin
      content, reduce scattering coefficient at 500 nm and the ratio of rayleigh
      scattering and the total scattering. Then tissue optical parameters in visible
      wavelengths were calculated. According to the tissue optical parameters and
      measured tissue diffusion spectrum, the intrinsic fluorescence spectrum was
      recovered from the measured fluorescence. Based on this, clinical trials were
      conducted to measure human skin fluorescence spectrum and diffusion reflectance
      spectrum, and then to recover skin intrinsic fluorescence spectrum. Finally, the
      accumulation of Advanced Glycation End products (AGE) in human skin was evaluated
      and the probability of diabetes mellitus was predicted. The result shows that the
      sensitivity and specificity were 69% and 0.75% respectively, when the measured
      fluorescent was used to screening diabetes mellitus. At the same specificity, the
      sensitivity was 90% when the recovered intrinsic fluorescence was employed to
      screening diabetes mellitus.

PMID- 30234953
TI  - [Studies on the Analytical Potential Energies for Partial Electronic States of
      Li(2) with Variational Algebraic Energy Consistent Method].
AB  - The full vibrational spectra especially those high-lying vibrational energies in
      the dissociation region of four specific electronic states 1(3)Delta(g),
      33Sigma(+)(g), 1(3)Sigma-(g) and b(3)Pi(u) have been obtained by using the
      improved variational algebraic method (VAM). The analytical potential energy
      functions (APEFs) of these electronic states are also determined with
      corresponding adjustable parameter lambda by using the variational algebraic
      energy consistent method (VAECM) based on the VAM vibrational spectra. The full
      vibrational energies, vibrational spectroscopic constants, force constants f(n),
      and expansion coefficients a(n) of the VAECM potential are also tabulated for
      each electronic state in this study. The results show that the VAECM analytical
      potentials are superior to some other widely used analytical ones, and do not
      have the unphysical tiny barriers existing in the precious AECM potentials.

PMID- 30234954
TI  - [Trace Moisture Measurement with 5.2 MUm Quantum Cascade Laser Based Continuous
      Wave Cavity Ring-Down Spectroscopy].
AB  - Trace moisture concentration in high-purity gases is an important parameter in
      semiconductor manufacturing because many manufacturing processes are sensitive to
      moisture even on the level of parts per billion by volume (ppbv). Detection of
      trace moisture in mid-infrared spectral region is beneficial due to more abundant
      and stronger spectral lines in this region. Recently, Quantum cascade lasers
      (QCLs) with high output power, narrow line-width, and high reliability have been
      developing rapidly and have become promising light sources for sensitive
      spectroscopic measurements. By employing a 5.2 MUm external-cavity tunable
      quantum cascade laser, a continuous-wave cavity ring-down spectroscopy (CRDS)
      experimental setup is established and applied to detect trace moisture in high
      purity nitrogen gas. In the experiment, the CRDS signal is averaged to improve
      the detection sensitivity, and the optimal averaging number is determined by
      Allan variance calculation to be 602. For trace moisture detection, the
      absorption cross-section of H(2)O in the spectral range between 1 905 and 1 925
      cm(-1) is simulated according to the HITRAN database and the optimal detection
      spectral line is chosen. Detected at 1 918 cm(-1) absorption line at 296 K
      temperature and 1 atm pressure, the measured moisture concentration is in good
      agreement with the nominal value, and the minimum detectable moisture
      concentration of 24.8 ppbv is achieved when cavity mirrors with reflectance of
      99.93% are used. The experimental results show that mid-infrared cavity ring-down
      spectroscopy technique has great potential in a wide variety of applications,
      such as industrial production control, environmental monitoring and health
      diagnosis, etc.

PMID- 30234956
TI  - [Terahertz Spectrum Features Extraction Based on Kernel Optimization Relevance
      Vector Machine].
AB  - Terahertz spectrum is sensitive to the change of the nonlocal molecular vibration
      mode. Accordingly, the spectral waveform is susceptible to variety of physical
      and chemical factors, which will lead to peak changes, frequency shifts, and even
      deformation of the overall waveform. Component analysis and material
      identification from the correspondence between the fixed peak features and
      materials will prone to cause errors or mistakes. Therefore, to solve this
      problem, we proposed a method based on Kernel Optimization Relevance Vector
      Machine (KO-RVM), which extracts global graphic features to distinct from the
      local features extraction method. And we use Support Vector Regression (SVR)
      algorithm as comparison. The result shows that, when basis functions' parameters
      of RVM are optimized with expectation-maximization algorithm, it will be suitable
      for feature extraction of terahertz transmission spectrum. The spectrum can be
      sparsely represented, and the amount of extracted graphic features is
      substantially reduced. Reconstruction models based on these features are capable
      of retaining the overall spectral characteristics, and fitting results for each
      band are more consistent, while the extracted spectrum features can be used as
      basis of similarity measurement and the common characteristics investigation
      between different materials.

PMID- 30234955
TI  - [Experimental Investigation on the Electron Temperature of Laser-Induced Mg
      Plasmas].
AB  - A series of plasma characteristic spectral lines of Mg alloy were obtained under
      nanosecond laser shock produced by a pulsed Nd : YAG laser (1 064 nm, maximum
      energy 500 mJ), which was taken under standard atmospheric pressure and at room
      temperature. Results indicated that the evolutionary rates of spectral lines were
      different, and the laser energy was enough to ionization Mg alloy under this
      experimental condition by the spectral lines of MgI, MgII. The electron
      temperature of Mg plasma were calculated by the measured relative Emission-line
      intensity(MgI383.2 nm, MgI470.3 nm, MgI518.4 nm). The experimental results showed
      that the secondary excitation Mg atoms could be got under this experimental
      condition. The electron temperature of Mg plasma decreased with the laser energy
      reduced while the laser energy was in the range of 200~500 mJ. When the laser
      energy was in the range of 350~500 mJ, the electron temperature changed rapidly.
      When the laser energy was in the range of 200~350 mJ, the electron temperature
      changed slowly and tended towards stability. It is found that when the laser
      energy was 300 mJ, the plasma temperature raised suddenly, which could not accord
      with the trend because of plasma shielding. When the laser energy was 300 mJ, the
      relative intensity of spectral lines was reduced which was lower than that of 350
      and 250 mJ. And it is against the variation trend of the relative intensity of
      spectral lines increases with the increase of laser energy, which prove plasma
      shielding phenomenon had occurred and plasma with high power laser separate the
      coupling between laser and material. The plasma temperature was increased
      significantly, which is not consistent with the trend .When the plasma shielding
      phenomenon happened, laser energy was absorbed by the plasma, resulting in the
      rise of plasma temperature.

PMID- 30234957
TI  - Performance Improvement in Low-Temperature-Processed Perovskite Solar Cells by
      Molecular Engineering of Porphyrin-Based Hole Transport Materials.
AB  - Porphyrin derivatives have recently emerged as hole transport layers (HTLs)
      because of their electron-rich characteristics. Although several successes with
      porphyrin-based HTLs have been recently reported, achieving excellent solar cell
      performance, the chances to improve this further by molecular engineering are
      still open. In this work, Zn porphyrin (PZn)-based HTLs were developed by
      conjugating fluorinated triphenylamine (FTPA) wings at the perimeter of the PZn
      core for low-temperature perovskite solar cells (L-PSCs). The fluorinated PZn
      HTLs (PZn-2FTPA and PZn-3FTPA) exhibited superior HTL properties compared to the
      nonfluorinated one (PZn-TPA). Moreover, their deeper highest occupied molecular
      orbital energy levels were beneficial for boosting open-circuit voltages, and
      their enhanced face-on stacking improved the hole transport properties. The L-PSC
      using PZn-2FTPA achieved the highest performance of 18.85%. Thus far, this result
      is one of the highest reported power conversion efficiencies among the PSCs using
      porphyrin-based HTLs.

PMID- 30234958
TI  - Molecularly Imprinted Artificial Biointerface for an Enzyme-Free Glucose
      Transistor.
AB  - A platform based on a highly selective and sensitive detection device
      functionalized with a well-designed artificial biointerface is required for
      versatile biosensors. We develop a molecularly imprinted polymer (MIP)-coated
      gate field-effect transistor (FET) biosensor for low-concentration glucose
      detection in biological fluid samples such as tears in an enzyme-free manner. The
      MIP includes glucose templates (GluMIP), in which glucose binds to
      vinylphenylboronic acid in the copolymerized membrane, resulting in the change in
      the density of molecular charges of the phenylboronic acid (PBA)/glucose complex.
      The FET biosensor can detect small biomolecules as long as biomolecular
      recognition events cause intrinsic changes in the density of molecular charges.
      As a result, the changes in the output voltage detected using the GluMIP-based
      FET sensor are fitted to the Langmuir adsorption isotherm equation at various
      concentrations of sugars, showing the low detection limit of 3 MUM and the high
      sensitivity of 115 mV/decade from 100 MUM to 4 mM glucose. On the basis of the
      equation, the stability constant ( Ka) of PBA with glucose is calculated and
      found to markedly increase to Ka = 1192 M-1, which is higher by a factor of a few
      hundreds than Ka = 4.6 M-1 obtained by nonelectrical detection methods. Moreover,
      the GluMIP-coated gate FET sensor shows an approximately 200-fold higher
      selectivity for glucose than for fructose. This is because glucose binds to PBA
      more selectively than fructose in the templates, resulting in the generation of
      negative charges. The electrical properties of the MIP-coated electrode are also
      evaluated by measuring capacitance. Our work suggests a new strategy of designing
      a platform based on the MIP-coated gate FET biosensor, which is suitable for a
      highly selective, sensitive, enzyme-free biosensing system.

PMID- 30234959
TI  - Metallic Nanoparticles Assimilation within Metal-Organic Framework Monolith.
AB  - A facile and versatile method is reported for the inclusion of gold nanoparticles
      (AuNPs) within a monolithic metal-organic framework (HKUST-1 MOF). Simple
      addition of stabilized colloidal AuNPs solution to the reaction mixture at the
      early stages of the formation of the MOF monolith resulted in quantitative uptake
      of the AuNPs within the MOF matrix. Several characterization techniques including
      solution and solid UV-vis spectroscopy, TEM, and XRD indicated the successful
      immobilization of the AuNPs. Controllable loading of AuNPs was also demonstrated,
      where gas sorption measurements indicated the maintained microporosity of the
      AuNPs-containing monoliths. This methodology has wide potential applications in
      demanding technologies, including sensing and catalysis, where monolithic
      materials of controllable physicochemical properties can be readily accessible
      through pore size and guest selectivity of the host MOF matrix controlling access
      of guest molecules to immobilized AuNPs.

PMID- 30234960
TI  - Modulating Hypoxia via Nanomaterials Chemistry for Efficient Treatment of Solid
      Tumors.
AB  - The common existence of hypoxia in solid tumors has been heavily researched
      because it renders tumors more resistant to most standard therapeutic methods,
      such as radiotherapy (RT), chemotherapy, and photodynamic therapy (PDT), and is
      associated with a more malignant phenotype and poor survival in patients with
      tumors. The development of hypoxia modulation methods for advanced therapeutic
      activity is therefore of great interest but remains a considerable challenge.
      Since the significant development of nanotechnology and nanomedicine,
      functionalized nanomaterials can be exploited as adjuvant "drugs" for these
      oxygen-dependent standard therapies or as hypoxia initiators for advanced new
      therapies to solid tumors. In this Account, we summarize our recent studies on
      the design and synthesis of nanomaterials with a set of desired chemistry
      benefits achievable by modulating hypoxia, suggesting a valid therapeutic option
      for tumors. The investigated strategies can be categorized into three groups: The
      first strategy is based on countering hypoxia. Considering that O2 deficiency is
      the major obstacle for the oxygen-dependent therapies, we initially developed
      methods to supply O2 by taking advantage of the hypoxia-responsive properties of
      nano-MnO2 or nanomaterials' photothermal effects for increased intratumoral blood
      flow. The second approach is to disregard hypoxia. Possible benefits of
      nanoagents include reducing/eliminating reliance on O2 or making O2 replacements
      as adjuvants to standard therapies. To this end, we investigated a nano
      upconversion/scintillator with the capacity toup-/down-convert near-infrared
      light (NIR)/X-ray to luminescence in the ultraviolet/visible region fortype-I PDT
      with minimized oxygen-tension dependency or developed Fe-based nanomaterials for
      chemodynamic therapy (CDT) without external energy and oxygen participation for
      efficient free radical killing of deep tumors. The third strategy involves
      exploiting hypoxia. The unique biological characteristics of hypoxia are
      exploited to activate nanoagents for new therapies. To address the discrepancy
      between the nanoagents' demand and supply within the hypoxia region, a smart
      "molecule-nano" medicine that stays small-molecule-like in the bloodstream and
      turns into self-assembled nanovesicles after entry into the hypoxia region was
      constructed for hypoxia-adaptive photothermal therapy (PTT). In addition to
      traditional anti-angiogenesis therapy, we prepared Mg2Si nanoparticles by a
      special self-propagating high-temperature synthesis approach. These nanoparticles
      can directly remove the intratumoral oxygen via the oxidation reactions of Mg2Si
      and later efficiently block the rapid reoxygenation via tumor blood vessels by
      the resultant SiO2 microsheets for cancer starvation therapy. Taken together,
      these findings indicate that nanomaterials will assume a valuable role for
      anticancer exploration based on either their properties to make up oxygen
      deficiency or the use of hypoxia for therapeutic applications.

PMID- 30234961
TI  - Inch-Scale Grain Boundary Free Organic Crystals Developed by Nucleation Seed
      Controlled Shearing Method.
AB  - Crystals of organic semiconductors are excellent candidates for flexible and
      array-based electronics. Large-scale synthesis of organic crystals in a
      controllable way while maintaining homogeneous single-crystal property has been a
      great challenge. The existence of grain boundaries and small crystal domains,
      however, restrict the device performance and limit the access to commercially
      viable organic electronics in the industry. Herein, we report the inch-scale
      synthesis of highly oriented 2,7-dioctyl[1]benzothieno[3,2- b][1]benzothiophene
      (C8-BTBT) organic single crystal by nucleation seed-controlled shearing method.
      The organic field-effect transistors developed from such single crystal have
      excellent carrier mobility as high as 14.9 cm2 V-1 s-1 and uniformity (standard
      deviation is 1.3 cm2 V-1 s-1) of 225 devices. We also found that the rotation of
      the principal axis in the crystal is governed by the orientations of seeds and
      the possible mechanism behind this phenomenon is proposed based on the density
      functional theory calculations. We anticipate that this proposed approach will
      have great potential to be developed as a platform for the growth of organic
      crystals with high crystallinity on a large scale.

PMID- 30234962
TI  - Suppressing Nonradiative Processes of Organic Dye with Metal-Organic Framework
      Encapsulation toward Near-Infrared Solid-State Microlasers.
AB  - Organic materials are an important class of gain media for fabricating
      miniaturized lasers because they combine fabrication simplicity with wide
      spectral coverage and tunability. However, progress toward near-infrared (NIR)
      organic solid-state lasers has been limited because of serious nonradiative
      processes originating from the severe intermolecular interaction in the condensed
      state. Here, we develop a strategy to realize room-temperature NIR microscale
      lasers through encapsulating organic dyes into the cavities of metal-organic
      frameworks (MOFs). The spatial confinement of the dye molecules within the MOF
      pores contributes to suppressing the multiple nonradiative processes (i.e.,
      aggregation-caused quenching and exciton-exciton annihilation). This results in a
      much higher radiative efficiency and thus much easier population inversion and
      low-threshold NIR lasing. Furthermore, the lasing wavelength can be further
      expanded based on the tailorable energy levels of the dye molecules. The results
      will provide useful enlightenment for the development of miniaturized NIR laser
      sources for new photonic applications.

PMID- 30234964
TI  - Combinatorial Study on Phase Formation and Oxidation in the Thin Film Superalloy
      Subsystems Co-Al-Cr and Co-Al-Cr-W.
AB  - Two Co-based superalloy subsystems, the ternary system Co-Al-Cr and the quasi
      ternary system Co-Al-Cr-W with a constant amount of 10 at. % W, were deposited as
      thin-film materials libraries and analyzed in terms of phase formation and
      oxidation behavior at 500  degrees C in air. By combining energy-dispersive X-ray
      analysis and X-ray photoelectron spectroscopy high-throughput composition
      measurements, a detailed evaluation of the dependence between the initial
      multinary metal composition and the oxide scale composition which is forming upon
      oxidation on the surface of the thin film is established. Phase maps for both
      materials libraries are provided by high-throughput X-ray diffraction. In
      addition, the oxidation of a Co-Al-Cr-W bulk sample was analyzed and compared to
      a corresponding film in the library.

PMID- 30234963
TI  - A Continuum of Proton-Coupled Electron Transfer Reactivity.
AB  - Proton-coupled electron transfer (PCET) covers a wide range of reactions
      involving the transfer(s) of electrons and protons. The best-known PCET reaction,
      hydrogen atom transfer (HAT), has been studied in detail for more than a century.
      HAT is generally described as the concerted transfer of a hydrogen atom (H* = H+
      + e-) from one group to another, Y + H-X -> Y-H + X, but a strict definition of
      HAT has been difficult to establish. Distinctions are more challenging when the
      transfer of "H*" involves e- and H+ that transfer to/from spatially distinct
      sites or even completely separate reagents (multiple-site concerted proton
      electron transfer, MS-CPET). MS-CPET reactivity is increasingly proposed in
      biological and synthetic contexts, and some reactions typically described as HAT
      more resemble MS-CPET. Despite that HAT and MS-CPET reactions "look different,"
      we argue here that these reactions lie on a reactivity continuum, and that they
      are governed by many of the same key parameters. This Account walks the reader
      across this PCET reactivity continuum, using a series of studies to show the
      strong similarities of reactions that move protons and electrons in seemingly
      different ways. To prepare for our stroll, we describe the thermochemical and
      kinetic frameworks for HAT and MS-CPET. The driving force for a solution HAT
      reaction is most easily discussed as the difference in the bond dissociation free
      energies (BDFEs) of the reactants and products. BDFEs can be analyzed as sums of
      electron and proton transfer steps and can therefore be obtained from p Ka and E
      degrees  values. Even though MS-CPET reactions do not make and break H-X bonds in
      the same way as HAT, the same thermochemical description can be used with the
      introduction of an effective BDFE (BDFEeff). The BDFEeff of a reductant/acid pair
      is the free energy of that pair to form H*, which can be obtained from p Ka and E
      degrees  values in an analogous fashion to a standard BDFE. When the PCET
      thermochemistry is known, HAT and PCET rate constants can be understood and often
      predicted using linear free energy relationships (the Bronsted catalysis law) and
      Marcus theory type approaches. After this background, we walk the reader through
      a continuum of PCET reactivity. Our journey begins with a study of metal-mediated
      HAT from hydrocarbon substrates to a metal-oxo complex and travels to the MS-CPET
      end of the reactivity spectrum, involving the transfer of H+ and e- from the
      hydroxylamine TEMPOH to two completely separate molecules. These examples, and
      those in between, are all analyzed within the same thermodynamic and kinetic
      framework. A description of the first examples of MS-CPET with C-H bonds uses the
      same framework and highlights the importance of hydrogen bonding and
      preorganization. The examples and analyses show that the reactions along the PCET
      continuum are more similar than they are different, and that attempts to divide
      these reactions into subcategories can obscure much of the essential chemistry.
      We hope that developing the many common features of these reactions will help
      experts and newcomers alike to explore exciting new territories in PCET
      reactivity.

PMID- 30234965
TI  - Highly Sensitive and Selective Biosensor for a Disaccharide Based on an AraC-Like
      Transcriptional Regulator Transduced with Bioluminescence Resonance Energy
      Transfer.
AB  - Sensitive and selective quantification of individual sugars in complex media is
      technically challenging and usually requires HPLC separation. Accurate
      measurement without the need for separation would be highly desirable. The
      measurement of trace levels of lactose in lactose-reduced milk exemplifies the
      problem, with the added challenge that trace lactose must be measured in the
      presence of ~140 mM glucose and galactose, the products of lactase digestion of
      lactose. Biosensing is an alternative to HPLC, but current biosensing methods,
      based on coupled-enzyme assays, tend to have poor sensitivity and complex
      biochemistry and can be time-consuming. We explored a fundamentally different
      approach, based on identifying a lactose-specific binding protein compatible with
      photonic transduction. We identified the BgaR transcriptional regulator of
      Clostridium perfringens, which is highly selective for lactose, as a suitable
      ligand binding domain and combined it with a bioluminescence energy resonance
      transfer transduction system. This BRET-based biosensor showed a 27% decrease in
      the BRET ratio in the presence of saturating (1 mM) lactose. Using a 5 min assay,
      the half maximal effective concentration (EC50) for lactose in phosphate-buffered
      saline (PBS) was 12 MUM. The biosensor was 200 times more sensitive to lactose
      than to glucose or galactose. Sensitivity and selectivity were not significantly
      affected by the presence of 10% (v/v) dialyzed milk. The biosensor is suitable
      for direct determination of residual lactose in lactase-treated milk, with a
      limit of detection of 0.2 MUM, 100 times below the most stringent lactose-free
      standard and without the need to remove fat or protein from the sample.

PMID- 30234966
TI  - All-Organic Conductive Biomaterial as an Electroactive Cell Interface.
AB  - Various attractive materials are being used in bioelectronics recently. In this
      paper, hydroxymethyl-3,4-ethylenedioxythiophene (EDOT-OH) has been in situ
      integrated and polymerized on the surface of the regenerated silk fibroin (RSF)
      film to construct a biocompatible electrode. In order to improve the efficiency
      of in situ polymerization, sodium dodecyl sulfate (SDS) was adopted as surfactant
      to construct a well-organized and stable poly(hydroxymethyl-3,4
      ethylenedioxythiophene) (PEDOT-OH) coating, whereas ammonium persulfate was used
      as oxidant. The effects of dosages of surfactant and oxidant, initial pH value,
      and monomer concentration on the polymerization were studied. Under the optimal
      conditions, the RSF/PEDOT-OH film exhibited a square resistance of 3.28 * 105
      Omega corresponding to a conductance of 6.1 * 10-3 S/cm. Scanning electron
      microscope images indicated that PEDOT-OH was deposited uniformly on the surface
      of the RSF film with SDS. Furthermore, Fourier transform infrared spectroscopy
      confirmed that interactions existed between the peptide linkages of silk fibroin
      (SF) macromolecules and PEDOT-OH. The RSF/PEDOT-OH film displayed favorable
      electrochemical stability, biocompatibility, and fastness. This study provides a
      feasible method to endow conductivity to RSF materials in various forms. In
      addition, the conductive layer and biocompatible silk substrate make the
      RSF/PEDOT-OH biomaterial highly suitable for potential applications in
      bioelectric devices, sensors, and tissue engineering.

PMID- 30234967
TI  - Correction to Weakly Trapped, Charged, and Free Excitons in Single-Layer MoS2 in
      the Presence of Defects, Strain, and Charged Impurities.

PMID- 30234968
TI  - DNA-Mediated Nanoscale Metal-Organic Frameworks for Ultrasensitive
      Photoelectrochemical Enzyme-Free Immunoassay.
AB  - A novel enzyme-free photoelectrochemical (PEC) immunoassay was developed for the
      ultrasensitive detection of prostate specific antigen (PSA) based on the DNA
      mediated nanoscale zirconium-porphyrin MOFs (NMOFs). By virtue of the intrinsic
      coordination between unsaturated zirconium sites of the NMOFs frameworks and
      phosphonate groups, the 5'-phosphorylared ss-DNA-tagged antibody (Ab-DNA)
      conjugate with a consecutive stretch of guanines as a spacer could be loaded on
      the NMOFs easily, obtaining a novel type of Ab-DNA-functionalized NMOFs complex.
      Additionally, as a photocathode PEC active nanomaterial, NMOFs exhibited a
      significant enhanced photocurrent response with the presence of dopamine under
      oxygen-containing aqueous media at -0.3 V (vs Ag/AgCl). Furthermore, with the aid
      of the electrochemical grafting of polyamidoamine (PAMAM) dendrimers
      functionalized interface, the novel type of Ab-DNA-NMOFs further served as a PEC
      signal nanoprobe for the ultrasensitive PSA immunoassay. Under optimal
      conditions, the corresponding immunosensor possessed a wide calibration range of
      1 pg mL-1 to 10 ng mL-1 and a limit of detection (LOD) of 0.2 pg mL-1. This
      present work demonstrated the promising application of DNA-mediated NMOFs in
      developing highly sensitive, environmentally friendly, and cost-effective PEC
      biosensors.

PMID- 30234969
TI  - Nucleus and Mitochondria Targeting Theranostic Plasmonic Surface-Enhanced Raman
      Spectroscopy Nanoprobes as a Means for Revealing Molecular Stress Response
      Differences in Hyperthermia Cell Death between Cancerous and Normal Cells.
AB  - Metallic plasmonic nanoparticles have been intensively exploited as theranostic
      nanoprobes for plasmonic photothermal therapy (PPT) and surface-enhanced Raman
      spectroscopy (SERS) applications. But the underlying molecular mechanisms
      associated with PPT-induced apoptosis between cancerous and normal cells have
      remained largely unknown or disputed. In this study, we designed an organelle
      targeting theranostic plasmonic SERS nanoprobe (CDs-Ag/Au NS) composed of porous
      Ag/Au nanoshell (p-Ag/Au NSs) and carbon dots (CDs) for nucleus and mitochondria
      targeted PPT of cells. The differences in molecular stress response in the PPT
      induced hyperthermia cell death between cancerous HeLa and normal L929 and H8
      cells have been revealed by site-specific single-cell SERS detection. The
      contents of tryptophan (Trp), phenylalanine (Phe), and tyrosine (Tyr) in HeLa
      cells were found more evidently increased than L929 and H8 cells during the PPT
      induced cell-death process. And from the mitochondria point of view, we found
      that the PPT-induced cell apoptosis for HeLa cells mainly stems from (or is
      regulated through) cellular thermal stress-responsive proteins, while for L929
      and H8 cells it seems more related to DNA. Understanding molecular stress
      response difference of the PPT-induced cell apoptosis between cancerous and
      normal cells is helpful for diagnosis and treatment of cancer, and the method
      will open an avenue for single-cell studies.

PMID- 30234970
TI  - Assembly of Multicomponent Protein Filaments Using Engineered Subunit Interfaces.
AB  - Exploiting the ability of proteins to self-assemble into architectural templates
      may provide novel routes for the positioning of functional molecules in
      nanotechnology. Here we report the engineering of multicomponent protein
      templates composed of distinct monomers that assemble in repeating orders into a
      dynamic functional structure. This was achieved by redesigning the protein
      protein interfaces of a molecular chaperone with helical sequences to create
      unique subunits that assemble through orthogonal coiled-coils into filaments up
      to several hundred nanometers in length. Subsequently, it was demonstrated that
      functional proteins could be fused to the subunits to achieve ordered alignment
      along filaments. Importantly, the multicomponent filaments had molecular
      chaperone activity and could prevent other proteins from thermal-induced
      aggregation, a potentially useful property for the scaffolding of enzymes. The
      design in this work is presented as proof-of-concept for the creation of modular
      templates that could potentially be used to position functional molecules,
      stabilize other proteins such as enzymes, and enable controlled assembly of
      nanostructures with unique topologies.

PMID- 30234971
TI  - Structures and Catalytic Activities of Complexes between Heme and All Parallel
      Stranded Monomeric G-Quadruplex DNAs.
AB  - Heme in its ferrous and ferric states [heme(Fe2+) and heme(Fe3+), respectively]
      binds selectively to the 3'-terminal G-quartet of all parallel-stranded monomeric
      G-quadruplex DNAs formed from inosine(I)-containing sequences, i.e.,
      d(TAGGGTGGGTTGGGTGIG) DNA(18mer) and d(TAGGGTGGGTTGGGTGIGA) DNA(18mer/A), through
      a pi-pi stacking interaction between the porphyrin moiety of the heme and the G
      quartet, to form 1:1 complexes [heme-DNA(18mer) and heme-DNA(18mer/A) complexes,
      respectively]. These complexes exhibited enhanced peroxidase activities, compared
      with that of heme(Fe3+) alone, and the activity of the heme(Fe3+)-DNA(18mer/A)
      complex was greater than that of the heme(Fe3+)-DNA(18mer) one, indicating that
      the 3'-terminal A of the DNA sequence acts as an acid-base catalyst that promotes
      the catalytic reaction. In the complexes, a water molecule (H2O) at the interface
      between the heme and G-quartet is coordinated to the heme Fe atom as an axial
      ligand and possibly acts as an electron-donating ligand that promotes heterolytic
      peroxide bond cleavage of hydrogen peroxide bound to the heme Fe atom, trans to
      the H2O, for the generation of an active species. The intermolecular nuclear
      Overhauser effects observed among heme, DNA, and Fe-bound H2O indicated that the
      H2O rotates about the H2O-Fe coordination bond with respect to both the heme and
      DNA in the complex. Thus, the H2O in the complex is unique in terms of not only
      its electronic properties but also its dynamic ones. These findings provide novel
      insights into the design of heme-deoxyribozymes and -ribozymes.

PMID- 30234972
TI  - Enhancing Light-Driven 1,3-Propanediol Production by Using Natural
      Compartmentalization of Differentiated Cells.
AB  - Synthetic biology emerges as a powerful approach for unlocking the potential of
      cyanobacteria to produce various chemicals. However, the highly oxidative
      intracellular environment of cyanobacteria is incompatible to numerous introduced
      enzymes from anaerobes. In this study, we explore a strategy based on natural
      compartmentalization of cyanobacterial heterocysts to overcome the
      incompatibility. Hence, the oxygen-sensitive 1,3-propanediol (1,3-PDO)
      biosynthetic pathway was selected as a model and insulated in heterocysts to
      evaluate the proposed strategy. Thus, the genes from different sources for 1,3
      PDO production were tandemly arrayed with promoter, resulting the assembled 1,3
      PDO synthetic cassettes. Then the synthetic cassettes were integrated into the
      chromosome of Anabaena sp. strain PCC7120 by homologous recombination,
      respectively. The engineered strain P11 containing the genes from facultative
      anaerobe Klebsiella pneumoniae (cassette KP) accumulated 46.0 mg L-1 of 1,3-PDO
      when heterocysts were present, which is approximately 1.7-fold higher than that
      of no heterocysts. As for the strains (P12, P13, and P14) containing the genes
      from strictly anaerobic bacterium Clostridium butyricum (cassette CB), the
      product 1,3-PDO could only be detected when heterocysts were present. These
      results indicate that insulation of the oxygen-sensitive 1,3-PDO pathway with
      heterocysts is an effective way to protect these enzymes in cyanobacteria. The
      strategy may have the potential of serving as a universal strategy to overcome
      the incompatibility of oxygen-sensitivity in synthetic biology.

PMID- 30234974
TI  - Magnetic-Based Microfluidic Device for On-Chip Isolation and Detection of Tumor
      Derived Exosomes.
AB  - Exosomes are membrane-enclosed phospholipid extracellular vesicles, which can act
      as mediators of intercellular communication. Although the original features endow
      tumor-derived exosomes great potential as biomarkers, efficient isolation and
      detection methods remain challenging. Here, we presented a two-stage microfluidic
      platform (ExoPCD-chip), which integrates on-chip isolation and in situ
      electrochemical analysis of exosomes from serum. To promote exosomes capture
      efficiency, an improved staggered Y-shaped micropillars mixing pattern was
      designed to create anisotropic flow without any surface modification. By
      combining magnetic enrichment based on specific phosphatidylserine-Tim4 protein
      recognition with a new signal transduction strategy in a chip for the first time,
      the proposed platform enables highly sensitive detection for CD63 positive
      exosomes as low as 4.39 * 103 particles/mL with a linear range spanning 5 orders
      of magnitude, which is substantially better than the existing methods. The
      reduced volume of sample (30 MUL) and simple affinity method also make it ideal
      for rapid downstream analysis of complex biofluids within 3.5 h. As a proof-of
      concept, we performed exosomes analysis in human serum and liver cancer patients
      can be well discriminated from the healthy controls by the ExoPCD-chip. These
      results demonstrate that this proposed ExoPCD-chip may serve as a comprehensive
      exosome analysis tool and potential noninvasive diagnostic platform.

PMID- 30234975
TI  - Vehicle-Based Methane Surveys for Finding Natural Gas Leaks and Estimating Their
      Size: Validation and Uncertainty.
AB  - Managing leaks in urban natural gas (NG) distribution systems is important for
      reducing methane emissions and costly waste. Mobile surveying technologies have
      emerged as a new tool for monitoring system integrity, but this new technology
      has not yet been widely adopted. Here, we establish the efficacy of mobile
      methane surveys for managing local NG distribution systems by evaluating their
      ability to detect and locate NG leaks and quantify their emissions. In two
      cities, three-quarters of leak indications from mobile surveys corresponded to NG
      leaks, but local distribution companies' field crews did not find most of these
      leaks, indicating that the national CH4 activity factor for leaks in local NG
      distribution pipelines is underestimated by a factor of 2.4. We found the median
      distance between mobile-estimated leak locations and actual leak locations was 19
      m. A comparison of emission quantification methods (mobile-based, surface
      enclosure, and tracer ratio) found that the mobile method overestimated leak
      magnitude for the smallest leaks but accurately estimated size for the largest
      leaks that are responsible for the majority of total emissions. Across leak
      sizes, mobile methods adequately rank relative emission rates for repair
      prioritization, and they are easily deployed and offer efficient spatial
      coverage.

PMID- 30234973
TI  - Bioengineered Norovirus S60 Nanoparticles as a Multifunctional Vaccine Platform.
AB  - Homotypic interactions of viral capsid proteins are common, driving viral capsid
      self-formation. By taking advantage of such interactions of the norovirus shell
      (S) domain that naturally builds the interior shells of norovirus capsids, we
      have developed a technology to produce 60-valent, icosahedral S60 nanoparticles
      through the E. coli system. This has been achieved by several modifications to
      the S domain, including an R69A mutation to destruct an exposed proteinase
      cleavage site and triple cysteine mutations (V57C/Q58C/S136C) to establish inter
      S domain disulfide bonds for enhanced inter-S domain interactions. The polyvalent
      S60 nanoparticle with 60 exposed S domain C-termini offers an ideal platform for
      antigen presentation, leading to enhanced immunogenicity to the surface-displayed
      antigens for vaccine development. This was proven by constructing a chimeric S60
      nanoparticle displaying 60 rotavirus (RV) VP8* proteins, the major RV
      neutralizing antigen. These S60-VP8* particles are easily produced and elicited
      high IgG response in mice toward the displayed VP8* antigens. The mouse antisera
      after immunization with the S60-VP8* particles exhibited high blockades against
      RV VP8* binding to its glycan ligands and high neutralizing activities against RV
      infection in culture cells. The three-dimensional structures of the S60 and S60
      VP8* particles were studied. Furthermore, the S60 nanoparticle can display other
      antigens, supporting the notion that the S60 nanoparticle is a multifunctional
      vaccine platform. Finally, the intermolecular disulfide bond approach may be used
      to stabilize other viral-like particles to display foreign antigens for vaccine
      development.

PMID- 30234976
TI  - Metabolic Susceptibility of 2-Chlorothioxanthone and Its Toxic Effects on mRNA
      and Protein Expression and Activities of Human CYP1A2 and CYP3A4 Enzymes.
AB  - Thioxanthones (TXs) are photoinitiators widely used in UV curable resins and food
      packaging, and their residues have been frequently detected in human bodies. Our
      current understanding of the susceptibility of residual TXs to metabolism and
      their effects on human health is very limited. The in vitro metabolism of TXs and
      its toxic effects on cytochrome P450 (CYP) (the key xenobiotic metabolizing
      enzymes) were examined in this study. 2-Chlorothioxanthone (2-Cl-TX)
      significantly inhibited the enzymatic activities of CYP1A2 and CYP3A4 with IC50
      of 8.36 and 0.86 MUM, respectively. The exposure to 2-Cl-TX at 2.5 MUM up
      regulated the mRNA expression of CYP1A2 and CYP3A4 in human hepatocellular
      carcinoma cells to 3.03-fold and 2.02-fold, respectively. 2-Cl-TX at 2.5 MUM
      caused 2.19-fold and 1.98-fold overexpression of CYP1A2 and CYP3A4, respectively.
      In vitro studies revealed that 2-Cl-TX was biotransformed into two metabolites
      through the sulfoxidation of the sulfur atom, or via the hydroxylation of
      aromatic carbon. Results from this study, including the metabolic susceptibility
      of residual 2-Cl-TX, the proposed metabolites and the significant toxic effect on
      the activities, mRNA, and protein expression of CYP1A2 and CYP3A4, are vital to
      the human health and safety risk assessment from this ubiquitous xenobiotic.

PMID- 30234977
TI  - Reactive Oxygen Species Formed by Secondary Organic Aerosols in Water and
      Surrogate Lung Fluid.
AB  - Reactive oxygen species (ROS) play a central role in adverse health effects of
      air pollutants. Respiratory deposition of fine air particulate matter can lead to
      the formation of ROS in epithelial lining fluid, potentially causing oxidative
      stress and inflammation. Secondary organic aerosols (SOA) account for a large
      fraction of fine particulate matter, but their role in adverse health effects is
      unclear. Here, we quantify and compare the ROS yields and oxidative potential of
      isoprene, beta-pinene, and naphthalene SOA in water and surrogate lung fluid
      (SLF). In pure water, isoprene and beta-pinene SOA were found to produce mainly
      OH and organic radicals, whereas naphthalene SOA produced mainly H2O2 and O2*-.
      The total molar yields of ROS of isoprene and beta-pinene SOA were 11.8% and 8.2%
      in water and decreased to 8.5% and 5.2% in SLF, which can be attributed to ROS
      removal by lung antioxidants. A positive correlation between the total peroxide
      concentration and ROS yield suggests that organic (hydro)peroxides may play an
      important role in ROS formation from biogenic SOA. The total molar ROS yields of
      naphthalene SOA was 1.7% in water and increased to 11.3% in SLF. This strong
      increase is likely due to redox reaction cycles involving environmentally
      persistent free radicals (EPFR) or semiquinones, antioxidants, and oxygen, which
      may promote the formation of H2O2 and the adverse health effects of anthropogenic
      SOA from aromatic precursors.

PMID- 30234978
TI  - Efficient Estimation of Formation Enthalpies for Closed-Shell Organic Compounds
      with Local Coupled-Cluster Methods.
AB  - Efficient estimation of the enthalpies of formation for closed-shell organic
      compounds via atom-equivalent-type computational schemes and with the use of
      different local coupled-cluster with single, double, and perturbative triple
      excitation (CCSD(T)) approximations was investigated. Detailed analysis of
      established sources of uncertainty, inclusive of contributions beyond frozen-core
      CCSD(T) and errors due to local CCSD(T) approximations and zero-point energy
      anharmonicity, suggests the lower limit of about 2 kJ.mol-1 for the expanded
      uncertainty of the proposed estimation framework. Among the tested computational
      schemes, the best-performing cases demonstrate expanded uncertainty of about 2.5
      kJ.mol-1, based on the analysis against 44 critically evaluated experimental
      values. Computational efficiency, accuracy commensurable with that of a typical
      experiment, and absence of the need for auxiliary reactions and additional
      experimental data offer unprecedented advantages for practical use, such as
      prompt validation of existing measurements and estimation of missing values, as
      well as resolution of experimental conflicts. The utility of the proposed
      methodology was demonstrated using a representative sample of the most recent
      experimental measurements.

PMID- 30234979
TI  - Ni-Catalyzed Enantioselective Reductive Diarylation of Activated Alkenes by
      Domino Cyclization/Cross-Coupling.
AB  - A Ni-catalyzed enantioselective reductive diarylation of activated alkenes by
      domino cyclizative/cross-coupling of two aryl bromides is developed. This
      reaction proceeds under very mild conditions and shows broad substrate scope,
      without requiring the use of preformed organometallic reagents. Moreover, this
      approach provides direct access to various bis-heterocycles bearing all-carbon
      quaternary centers in synthetically useful yields (up to 81%) with excellent
      enantioselectivity (>30 examples, 90-99% ee).

PMID- 30234980
TI  - Toxicological Risk by Inhalation Exposure of Air Pollution Emitted from China's
      Municipal Solid Waste Incineration.
AB  - Municipal solid waste (MSW) incineration has developed rapidly in China. However,
      the air pollution-related health risks attributable to MSW incinerators are still
      far from known. In this context, an MSW incineration emission inventory was
      compiled using plant-level activity data and localized emission factors.
      Subsequently, Gaussian Plume Model and Risk Quotients Model were utilized to
      calculate the spatialized hazard index (HI) and carcinogenic risk (CR).
      Altogether, 76449 tons (t) of NO X, 25725 t of SO2, 16937 t of CO, 9279 t of HCl,
      5629 t of particulate matter, 33 t of Cr, 33 t of Pb, 20 t of Hg, 6 t of Cd, 4 t
      of Ni, 0.4 t of As, and 94 g-toxic equivalent quantity of polychlorinated dibenzo
      p-dioxins and polychlorinated dibenzofurans were emitted in 2015. The national
      average HI was 1.88 * 10-2, which was far lower than the acceptable level (HI <=
      1). However, the national average CR was 5.71 * 10-6, which was approximately
      five times higher than the acceptable level (CR <= 1 * 10-6). The spatial
      heterogeneity of health risks was observed. The results enrich spatial dimensions
      of prior estimates and provide policy implications from the aspects of
      accelerating technology upgrades, strengthening emission standards, optimizing
      site selection and enhancing risk communication.

PMID- 30234981
TI  - Role of Photoisomerization on the Photodetachment of the Photoactive Yellow
      Protein Chromophore.
AB  - The photocycle of photoactive yellow protein (PYP) is initiated by a photoinduced
      trans-cis isomerization around a C?C bond in the chromophore that lies at the
      heart of the protein; however, in addition to the desired photochemical pathway,
      the chromophore can undergo competing electronic relaxation processes. Here we
      combine gas-phase anion photoelectron spectroscopy and quantum chemistry
      calculations to investigate how locking the C?C bond in the chromophore controls
      the competition between these electronic relaxation processes following
      photoexcitation in the range 400-310 nm. We find evidence to suggest that
      preventing trans-cis isomerization effectively turns off internal conversion to
      the ground electronic state and enhances electron emission from the first
      electronically excited state.

PMID- 30234982
TI  - Concave-Convex pi-pi Template Approach Enables the Synthesis of
      [10]Cycloparaphenylene-Fullerene [2]Rotaxanes.
AB  - The cycloparaphenylenes (CPPs) are a class of strained macrocycles that until
      2008 were considered beyond the reach of organic synthesis. With its cyclic array
      of ten para-substituted phenylene rings, [10]CPP possesses a concave pi-system
      that is perfectly preorganized for the strong supramolecular association of
      convex fullerenes such as C60. Although mechanically interlocked CPP
      architectures have been observed in the gas phase, the rational synthesis of bulk
      quantities has not been achieved yet, which is likely due to the fact that
      conventional template strategies are not amenable to CPP rings that lack
      heteroatoms. Here, we report the synthesis of two [2]rotaxanes in which a [10]CPP
      ring binds to a central fullerene bis-adduct and is prevented from dethreading by
      the presence of two bulky fullerene hexakis-adduct stoppers. The final step in
      the rotaxane synthesis is surprisingly efficient (up to ca. 40% yield) and
      regioselective because the fullerene acts as an efficient convex template, while
      [10]CPP acts as a supramolecular directing group, steering the reaction at the
      central fullerene exclusively toward two trans regioisomers. Comprehensive
      physicochemical studies confirmed the interlocked structure, shed light on the
      dynamic nature of the CPP-fullerene interaction, and revealed intriguing
      consequences of the mechanical bond on charge transfer processes. In light of
      recent advances in the synthesis of nanohoops and nanobelts, our concave-convex
      pi-pi templating strategy may be broadly useful and enable applications in
      molecular electronics or complex molecular machinery.

PMID- 30234983
TI  - Discovery of Novel 7-Aryl 7-Deazapurine 3'-Deoxy-ribofuranosyl Nucleosides with
      Potent Activity against Trypanosoma cruzi.
AB  - Chagas disease is the leading cause of cardiac-related mortality in Latin
      American countries where it is endemic. Trypanosoma cruzi, the disease-causing
      pathogen, is unable to synthesize purines de novo, necessitating salvage of
      preformed host purines. Therefore, purine and purine-nucleoside analogues might
      constitute an attractive source for identifying antitrypanosomal hits. In this
      study, structural elements of two purine-nucleoside analogues (i.e., cordycepin
      and a recently discovered 7-substituted 7-deazaadenosine) led to the
      identification of novel nucleoside analogues with potent in vitro activity. The
      structure-activity relationships of substituents at C-7 were investigated,
      ultimately leading to the selection of compound 5, with a C-7 para-chlorophenyl
      group, for in vivo evaluation. This derivative showed complete suppression of T.
      cruzi Y-strain blood parasitemia when orally administered twice daily for 5 days
      at 25 mg/kg and was able to protect infected mice from parasite-induced
      mortality. However, sterile cure by immunosuppression could not be demonstrated.

PMID- 30234984
TI  - Modified Gaussian Wave Packet Method for Calculating Initial State Wave Functions
      in Photodissociation.
AB  - A modified Gaussian wave packet relaxation method is proposed to calculate the
      ground state wave function using an expansion of frozen Gaussian wave packets.
      This new procedure consists of two steps. In the first step, a multidimensional
      Gaussian product placed at the ground state equilibrium geometry is propagated in
      imaginary time. The relaxation optimizes the widths of the one-dimensional
      Gaussians. In the second step, additional Gaussian wave packets with the same
      widths are placed near the equilibrium geometry, and the corresponding expansion
      coefficients are optimized using the same relaxation method. This new algorithm
      is tested in photodissociation of NOCl and NH3, and the results show good
      agreement with the exact results in the energy, wave function, and absorption
      spectrum. In particular, the highly structured absorption spectrum of NH3 is
      reproduced, underscoring the accuracy of both the initial wave packet and the
      excited state propagation.

PMID- 30234985
TI  - Direct Synthesis of a Dioxabenzobicyclo[3.2.1]octane Core from Salicylaldehydes.
AB  - A copper(II) trifluoromethanesulfonate via Prins reaction between
      salicylaldehydes and allyl alcohols is realized under mild conditions. A series
      of compounds containing dioxabenzobicyclo[3.2.1]octane motifs are obtained in
      moderate to good yields. The current method can efficiently construct the
      valuable structural motif from easily accessed starting materials, providing a
      smooth method to build benzobicyclo skeletons.

PMID- 30234987
TI  - How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin
      Dependent Kinases?
AB  - Cyclin-dependent kinases (CDKs) are an important and emerging class of drug
      targets for which many small-molecule inhibitors have been developed. However,
      there is often insufficient data available on the selectivity of CDK inhibitors
      (CDKi) to attribute the effects on the presumed target CDK to these inhibitors.
      Here, we highlight discrepancies between the kinase selectivity of CDKi and the
      phenotype exhibited; we evaluated 31 CDKi (claimed to target CDK1-4) for activity
      toward CDKs 1, 2, 4, 5, 7, 9 and for effects on the cell cycle. Our results
      suggest that most CDKi should be reclassified as pan-selective and should not be
      used as a tool. In addition, some compounds did not even inhibit CDKs as their
      primary cellular targets; for example, NU6140 showed potent inhibition of Aurora
      kinases. We also established an online database of commercially available CDKi
      for critical evaluation of their utility as molecular probes. Our results should
      help researchers select the most relevant chemical tools for their specific
      applications.

PMID- 30234986
TI  - Bio-based Large Tablet Controlled-Release Urea: Synthesis, Characterization, and
      Controlled-Released Mechanisms.
AB  - To improve nitrogen (N) use efficiency and minimize environmental pollution
      caused by fertilizer overuse, novel bio-based large tablet controlled-release
      urea (LTCRU) was prepared using bio-based coating materials to coat large tablet
      urea (LTU) derived from urea prills (U). Nano fumed silica (NFS) was added to the
      bio-based coating materials to improve the slow-release properties. The surface
      area of the LTU and U was measured by three-dimensional scanning. In comparison
      to U, LTU had a smaller surface area/weight ratio, which can reduce the coating
      materials. Scanning electron microscopy analysis showed that the addition of NFS
      in bio-based coating materials reduced the porosity of the coating shells of
      LTCRUs and, thus, enhanced the N release longevity of the controlled-released
      fertilizer. Dependent upon the pores on the coating shells of LTCRU, two N
      release patterns were revealed. Because of the good release characteristics, the
      novel LTCRU shows great potential to support sustainable agricultural production.

PMID- 30234988
TI  - Competing Dispersive Interactions: From Small Energy Differences to Large
      Structural Effects in Methyl Jasmonate and Zingerone.
AB  - Modern structural studies of biologically relevant molecules require an
      exhaustive interplay between experiment and theory. In this work, we present two
      examples where a poor choice of the theoretical method led to a misinterpretation
      of experimental results. We do that by performing a rotational spectroscopy study
      on two large and flexible biomolecules: methyl jasmonate and zingerone. The
      results show the enormous potential of rotational spectroscopy as a benchmark to
      evaluate the performance of theoretical methods.

PMID- 30234989
TI  - Electrolyte-Induced Electrical Disconnection between Single Graphene
      Nanoplatelets and an Electrode.
AB  - We report the influence of electrolyte on the electrical contact between graphene
      nanoplatelets (GNPs) and an electrode via a single entity electrochemical
      technique. The current "steps" were observed in the absence of electrolyte due to
      the GNPs impacting on and bridging across an interdigitated gold electrode array
      (IDE); in contrast, current spikes of short duration were obtained in the
      presence of electrolyte. This result indicates that in the latter case the
      constant short-circuit bridging current was switched off and replaced solely by
      impacts of GNPs with single electrodes. These observed current spikes measured in
      the presence of electrolyte are evidenced to be of a capacitative nature,
      demonstrating the high sensitivity of the electronic properties of the GNP/metal
      junction to the ionic strength of the electrolytic solution.

PMID- 30234990
TI  - Diastereoselective Synthesis of Tetrahydroquinolines via [4 + 2] Annulation
      between in Situ Generated p-Quinone Methides and Nitroalkenes.
AB  - A formal [4 + 2] annulation reaction between in situ generated p-quinone methides
      and nitroalkenes via an aza-Michael/1,6-conjugate addition reaction sequence has
      been developed in which manganese dioxide is used as the oxidant to promote in
      situ formation of o-tosylaminophenyl-substituted p-QMs. Under mild conditions,
      this unprecedented cascade reaction readily occurs in good yield, providing
      straightforward access to a series of 4-aryl-substituted tetrahydroquinolines.

PMID- 30234991
TI  - Temperature-Dependent Structural Changes in Liquid Benzene.
AB  - Benzene is the simplest aromatic molecule with intermolecular pi-pi interactions.
      Because ordered liquids are key structures used to study chemical and biological
      phenomena in the liquid state, ordered structures of benzene confined in
      nanopores have been extensively studied, whereas those in the liquid state are
      still unknown. In this study, we address fundamental questions regarding whether
      ordered structures of benzene are formed in the liquid state by using carbon K
      edge X-ray absorption spectroscopy (XAS) as a sensitive local probe. By comparing
      unexpected temperature behaviors of the pi* peak in XAS spectra with model
      calculations, we have investigated temperature-dependent changes of ordered
      structures in liquid benzene caused by the increase in abundance of the parallel
      sandwich orientation relative to parallel displaced structures for the higher
      temperature. These results are confirmed by infrared spectroscopy with additional
      support of vibrational mode calculations.

PMID- 30234992
TI  - Combination Therapy with DETA/NO and Clopidogrel Inhibits Metastasis in Murine
      Mammary Gland Cancer Models via Improved Vasoprotection.
AB  - Vascular endothelial dysfunction and platelet activation play a key role in tumor
      metastasis, and therefore, both of these processes are considered important
      therapeutic targets in cancer. The aim of our studies was to analyze
      antimetastatic activity of combination therapy using nitric oxide donor DETA/NO
      and antiplatelet drug clopidogrel. Nitric oxide acts as a vasoprotective
      mediator, while clopidogrel inhibits ADP-mediated platelet aggregation. 4T1-luc2
      tdTomato cell line transplanted intravenously (i.v.) and 4T1 cell line
      transplanted orthotopically were used as metastatic mammary gland cancer models.
      Moreover, antiaggregation action of compounds was tested ex vivo on the blood
      samples taken from breast cancer patients. We have shown that in selected dosage
      regimes, DETA/NO combined with clopidogrel significantly reduced lung metastatic
      foci formation in an i.v. model, and such inhibition was transiently observed
      also in an orthotopic model. The antimetastatic effect was correlated with a
      significant increase of prostacyclin (PGI2) metabolite and reduction of
      endothelin-1, sE-selectin, sI-CAM, and TGF-beta plasma levels as well as
      decreased V-CAM expression on the endothelium. Combination therapy decreased
      fibrinogen binding to the resting platelets at the early stage of tumor
      progression (day 14). However, at the later stages (days 21 and 28), the markers
      of platelet activation were detected (increased JON/A antibody bound, P-selectin
      level, binding of fibrinogen, and vWf). Decreased aggregation as well as a lower
      release of TGF-beta were detected in platelets incubated ex vivo with compounds
      tested from metastatic breast cancer patients. Although combination therapy
      increases E-cadherin, the increase of N-cadherin and alpha-SMA in tumor tissue
      was also observed. The results showed that at the early stages of tumor
      progression, combined therapy with DETA/NO and clopidogrel improves
      vasoprotective and antiplatelet activity. However, in advanced tumors, some
      adverse effects toward platelet activation can be observed.

PMID- 30234993
TI  - Well-Defined Phosphine-Free Iron-Catalyzed N-Ethylation and N-Methylation of
      Amines with Ethanol and Methanol.
AB  - An iron(0) complex bearing a cyclopentadienone ligand catalyzed N-methylation and
      N-ethylation of aryl and aliphatic amines with methanol or ethanol in mild and
      basic conditions through a hydrogen autotransfer borrowing process is reported. A
      broad range of aromatic and aliphatic amines underwent mono- or dimethylation in
      high yields. DFT calculations suggest molecular hydrogen acts not only as a
      reducing agent but also as an additive to displace thermodynamic equilibria.

PMID- 30234994
TI  - Bile Salts: Natural Surfactants and Precursors of a Broad Family of Complex
      Amphiphiles.
AB  - Bile salts (BSs) are naturally occurring rigid surfactants with a steroidal
      skeleton and specific self-assembly and interface behaviors. Using bile salts as
      precursors, derivatives can be synthesized to obtain molecules with specific
      functionalities and amphiphilic structure. Modifications on single molecules are
      normally performed by substituting the least-hindered hydroxyl group on carbon C
      3 of the steroidal A ring or at the end of the lateral chain. This leads to
      monosteroidal rigid building blocks that are often able to self-organize into 1D
      structures such as tubules, twisted ribbons, and fibrils with helical
      supramolecular packing. Tubular aggregates are of particular interest, and they
      are characterized by cross-section inner diameters spanning a wide range of
      values (3-500 nm). They can form through appealing pH- or temperature-responsive
      aggregation and in mixtures of bile salt derivatives to provide mixed tubules
      with tunable charge and size. Other derivatives can be prepared by covalently
      linking two or more bile salt molecules to provide complex systems such as
      oligomers, dendrimers, and polymeric materials. The unconventional amphiphilic
      molecular structure imparts specific features to BSs and derivatives that can be
      exploited in the formulation of capsules, drug carriers, dispersants, and
      templates for the synthesis of nanomaterials.

PMID- 30234995
TI  - Diborene: Generation and Photoelectron Spectroscopy of an Inorganic Biradical.
AB  - Diborenes, R-BB-R', are of current interest in inorganic chemistry because they
      offer the opportunity to tune the properties of a biradical by modifying the
      substituents of the diborene parent, HBBH. Here we synthesize the elusive
      diborene by H atom abstraction from diborane, B2H6, using fluorine atoms and
      report a vibrationally resolved photoelectron spectrum of the HBBH biradical. The
      spectrum is interpreted by comparison with high-level ab initio computations,
      taking into account the Renner-Teller splitting in the X+ 2Pi ionic ground state,
      which show an excellent agreement with the experimental spectrum. An adiabatic
      ionization energy of 9.080 +/- 0.015 eV was determined, and a vibrational
      progression in the boron-boron stretching vibration of 0.14 eV is visible. This
      is due to the reduction of bond order upon ionization, accompanied by an increase
      of the computed boron-boron bond length, RBB, from 1.514 to 1.606 A.

PMID- 30234996
TI  - Simple and Reliable Method for Studying the Adsorption Behavior of Aquivion
      Ionomers on Carbon Black Surfaces.
AB  - A better understanding of the interactions of carbon black and perfluorinated
      sulfonic acid (PFSA) ionomer helps to improve the effectiveness of polymer
      electrolyte membrane fuel cells. We present a simple and fast method for
      quantitative PFSA ionomer analysis based on suspension density measurements.
      After validation of the reliability of our method by thermogravimetric analysis
      and isothermal titration calorimetry (ITC), we investigate the adsorption
      equilibrium of short-side-chain PFSA ionomers of different equivalent weights
      (EW) and polarities on carbon black. The measured adsorption isotherms exhibit a
      plateau in the ionomer surface concentration for ionomer equilibrium
      concentrations <=2 g/L. In this concentration range, the adsorption isotherms are
      described by the Langmuir model, whereby the surface concentrations in the
      plateau region are between 0.041 and 0.070 g/g. The plateau value of the ionomer
      surface concentration increases with EW and therefore with decreasing number of
      side chains with terminal sulfonic acid group per ionomer molecule, while the
      amount of adsorbed sulfonic acid groups remains constant for all investigated
      ionomers, resulting in similar zeta-potentials and sedimentation stability of the
      suspensions. The free energies of adsorption Delta G calculated from the
      association constants of the adsorption isotherms agree well with Delta G values
      obtained by isothermal titration calorimetry (ITC) and thus validate the
      adsorption isotherm measurement method. From the values of adsorption enthalpy
      Delta H ((-7.3 +/- 0.8) kJ/mol) and entropy Delta S (ca. 100 J/(mol K)), which
      were extracted from ITC, we conclude that the ionomer adsorption on carbon black
      is a spontaneous physisorption process.

PMID- 30234997
TI  - Surgical Volume and Postoperative Complications of Acromioclavicular Joint
      Separations: Analysis of the ABOS Part II Examination.
AB  - BACKGROUND:: High-grade acromioclavicular (AC) joint separations are relatively
      rare injuries that are often treated surgically, yet more information is needed
      about the risks of various surgical procedures in terms of considering and
      counseling patients regarding operative versus nonoperative treatment. PURPOSE::
      To calculate whether the volume of surgical treatment of AC joint separations
      increased over a recent 12-year period; to examine the nature and frequency of
      complications, reoperations, and readmissions associated with these procedures;
      and to assess whether patient- and surgeon-specific factors or surgical technique
      affected these rates. STUDY DESIGN:: Cross-sectional study; Level of evidence, 3.
      METHODS:: The American Board of Orthopaedic Surgery (ABOS) database for
      orthopaedic surgeons taking the Part II examination was reviewed from 2005 to
      2016 to identify surgical treatment of AC joint separations. The authors
      calculated the percentage of all surgical cases in the ABOS database and rates of
      complications, reoperations, and readmissions. Association of these sequelae with
      patient- and surgeon-specific factors and surgical techniques was assessed.
      RESULTS:: There was no difference in the number or percentage of cases per year
      over the study period. There was an overall complication rate of 24.5%, a
      reoperation rate of 7.3%, and a readmission rate of 1.9%. Patients >=40 years of
      age had significantly higher complication, reoperation, and readmission rates as
      compared with patients <40 years of age. There were significant differences in
      complication, reoperation, readmission, and displacement rates dependent on the
      type of surgical procedure performed. The highest complication rates were seen
      with open suspensory fixation, screw fixation, open reduction internal fixation,
      and arthroscopic coracoclavicular ligament repair or reconstruction. The highest
      reoperation rates were seen with screw fixation, open reduction internal
      fixation, and open suspensory fixation. CONCLUSION:: The volume of surgical
      treatment for AC joint separations did not change significantly over the study
      period. Complication, reoperation, and readmission rates were dependent on the
      type of surgical procedure performed and patient age. This information should
      assist surgeons in discussing risks when considering and counseling patients
      regarding operative versus nonoperative treatment.

PMID- 30234998
TI  - Urinary acrolein metabolite levels in severe acute alcoholic hepatitis patients.
AB  - Alcohol-associated liver disease (ALD) remains a major health concern worldwide.
      Alcohol consumption gives rise to reactive/toxic acrolein, a pathogenic mediator
      of liver injury in experimental ALD. Elevated acrolein adducts and metabolites
      are detectable in blood and urine. This study evaluates the major urinary
      acrolein metabolite, 3-hydroxypropylmercapturic acid (HPMA), in patients with
      acute alcoholic hepatitis (AAH), and examines its association with disease
      severity, and markers of hepatic inflammation and injury. Urine HPMA was
      significantly higher in severe (MELD>=20) AAH patients compared to non-severe AAH
      (MELD<=19), or non-alcohol-consuming controls, suggesting that urine HPMA is a
      novel non-invasive biomarker in severe AAH. The association between HPMA and MELD
      in AAH patients was nonlinear. In non-severe patients, there was a positive
      trend, although not significant, while in severe AAH the association was
      negative, indicative of extensive injury and glutathione depletion. Consistent
      with the multifactorial etiology of ALD, our data identified strong combined
      effects of HPMA and proinflammatory cytokines on hepatocyte cell death, thereby
      supporting the pathogenic role of acrolein in liver injury. HPMA, together with
      IL-1beta, showed robust associations with CK18-M30 (adjusted R2=0.812, p=0.016)
      and CK18-M65 (adjusted R2=0.670, p=0.048); similarly HPMA, with IL-8, correlated
      with CK18-M30 (adjusted R2=0.875, p=0.007) and CK18-M65 (adjusted R2=0.831,
      p=0.013). The apoptosis index (CK18-M30:CK18-M65 ratio) strongly correlated with
      HPMA, together with IL-1beta (adjusted R2=0.777, p=0.022) or TNFalpha (adjusted
      R2=0.677, p=0.046). In severe AAH patients, IL-1beta, IL-8 and TNFalpha are the
      predominant proinflammatory cytokines that interact with HPMA, and play important
      mediating roles in influencing the extent/pattern of liver cell death.

PMID- 30234999
TI  - Clinical and Structural Evaluations of Rotator Cuff Repair With and Without Added
      Platelet-Rich Plasma at 5-Year Follow-up: A Prospective Randomized Study.
AB  - BACKGROUND:: Platelet-rich plasma (PRP) has been studied with the objective of
      reducing the retear rate and improving functional outcomes after rotator cuff
      repair. Only one study to date has reported its midterm effect. HYPOTHESIS:: PRP
      promotes better functional and structural results in arthroscopic rotator cuff
      repair. STUDY DESIGN:: Randomized controlled trial; Level of evidence, 2.
      METHODS:: All patients underwent arthroscopic single-row repair of small to
      medium supraspinatus tears. At the end of the surgical procedure, liquid PRP
      prepared by apheresis with autologous thrombin was applied in the tendon-to-bone
      interface in the PRP group. The outcomes were assessed by the University of
      California, Los Angeles (UCLA) and Constant scales and the visual analog scale
      (VAS) for pain at 6, 12, 24, and 60 months after surgery and magnetic resonance
      imaging at 12 and 60 months. RESULTS:: Of 54 patients initially randomized, we
      analyzed the clinical outcomes in 51 (25 control, 26 PRP) and the structural
      outcomes in 44 (22 each group). At 60-month follow-up, the mean UCLA scores were
      32.5 +/- 3.8 and 32.1 +/- 4.6 in the control and PRP groups, respectively ( P =
      .992). The mean Constant scores were 82.0 +/- 9.5 in the control group and 82.1
      +/- 11.0 in the PRP group ( P = .699). The mean VAS scores were 1.4 +/- 1.8 and
      1.5 +/- 2.1 in the control and PRP groups, respectively ( P = .910). None of the
      clinical assessments at 6, 12, and 24 months in either group produced
      statistically significant differences, and both groups showed significant
      improvements throughout the follow-up time in the 3 evaluations ( P < .001). The
      control group exhibited 1 full-thickness retear (Sugaya type IV) and 11 partial
      thickness retears (Sugaya type III), while the PRP group had 7 partial-thickness
      retears (Sugaya type III). The overall number of retears did not differ between
      groups ( P = .203). CONCLUSION:: PRP obtained by apheresis and applied in liquid
      form with the addition of thrombin at the end of single-row repair of
      supraspinatus tears did not promote better clinical or structural results at 60
      month follow-up. REGISTRATION:: NCT01029574 ( ClinicalTrials.gov identifier).

PMID- 30235001
TI  - Use of Masks in Cystic Fibrosis Patients.

PMID- 30235002
TI  - Cancer Cachexia: Identification by Clinical Assessment versus International
      Consensus Criteria in Patients with Metastatic Colorectal Cancer.
AB  - BACKGROUND: Cancer cachexia is associated with poorer outcomes and is often
      diagnosed by the Fearon criteria. Oncologists clinically identify cachexia based
      on a patient's presentation. In this study agreement between these identification
      methods was evaluated and associations with outcomes were studied in patients
      with metastatic colorectal cancer. METHODS: Fearon criteria comprised weight loss
      >5% OR weight loss >2% with either BMI <20 kg/m2 or sarcopenia (determined by CT
      imaging). Clinical assessment by the oncologist was based on the patient's
      clinical presentation. Agreement was tested with Kappa. Associations with
      treatment tolerance and progression free survival (PFS) were tested with logistic
      regressions and Cox proportional hazards, respectively. RESULTS: Of 69 patients,
      52% was identified as cachectic according to Fearon criteria and 9% according to
      clinical assessment. Agreement between both methods was slight (Kappa 0.049, P =
      0.457). Clinically cachectic patients had a shorter PFS than clinically non
      cachectic patients (HR 3.310, P = 0.016). No other differences in outcomes were
      found between cachectic vs. non-cachectic patients using both methods.
      CONCLUSIONS: The agreement between cancer cachexia identification by clinical
      assessment vs. Fearon criteria was slight. Further improvement of cachexia
      criteria is necessary to identify cachectic patients at risk of poorer outcomes,
      who may benefit from targeted cachexia interventions.

PMID- 30235003
TI  - Scoring Depression on a Common Metric: A Comparison of EAP Estimation, Plausible
      Value Imputation, and Full Bayesian IRT Modeling.
AB  - There are a growing number of item response theory (IRT) studies that calibrate
      different patient-reported outcome (PRO) measures, such as anxiety, depression,
      physical function, and pain, on common, instrument-independent metrics. In the
      case of depression, it has been reported that there are considerable mean score
      differences when scoring on a common metric from different, previously linked
      instruments. Ideally, those estimates should be the same. We investigated to what
      extent those differences are influenced by different scoring methods that take
      into account several levels of uncertainty, such as measurement error (through
      plausible value imputation) and item parameter uncertainty (through full Bayesian
      IRT modeling). Depression estimates from different instruments were more similar,
      and their corresponding confidence/credible intervals were larger when plausible
      value imputation or Bayesian modeling was used, compared to the direct use of
      expected a posteriori (EAP) estimates. Furthermore, we explored the use of
      Bayesian IRT models to update item parameters based on newly collected data.

PMID- 30235000
TI  - The Effect of Digital Breast Tomosynthesis Adoption on Facility-Level Breast
      Cancer Screening Volume.
AB  - OBJECTIVE: The purpose of this study was to determine whether digital breast
      tomosynthesis (DBT) adoption was associated with a decrease in screening
      mammography capacity across Breast Cancer Screening Consortium facilities, given
      concerns about increasing imaging and interpretation times associated with DBT.
      SUBJECTS AND METHODS: Facility characteristics and examination volume data were
      collected prospectively from Breast Cancer Screening Consortium facilities that
      adopted DBT between 2011 and 2014. Interrupted time series analyses using Poisson
      regression models in which facility was considered a random effect were used to
      evaluate differences between monthly screening volumes during the 12-month
      preadoption period and the 12-month postadoption period (with the two periods
      separated by a 3-month lag) and to test for changes in month-to-month facility
      level screening volume during the preadoption and postadoption periods. RESULTS:
      Across five regional breast imaging registries, 15 of 83 facilities (18.1%)
      adopted DBT for screening between 2011 and 2014. Most had no academic affiliation
      (73.3% [11/15]), were nonprofit (80.0% [12/15]), and were general radiology
      practices (66.7% [10/15]). Facility-level monthly screening volumes were slightly
      higher during the postadoption versus preadoption periods (relative risk [RR],
      1.09; 95% CI, 1.06-1.11). Monthly screening volumes remained relatively stable
      within the preadoption period (RR, 1.00 per month; 95% CI 1.00-1.01 per month)
      and the postadoption period (RR, 1.00; 95% CI, 1.00-1.01 per month). CONCLUSION:
      In a cohort of facilities with varied characteristics, monthly screening
      examination volumes did not decrease after DBT adoption.

PMID- 30235005
TI  - Induced carotid atherosclerosis in lupus mice.
AB  - Fas knockout (Fas-/-) mice are a model for systemic lupus erythematosus (SLE) 
      like autoimmune syndromes. We aimed to induce atherosclerosis (AS) in Fas-/-
      mice. Sixteen male Fas-/- mice were included in the study, sex-matched C57B6/L
      (B6) and apolipoprotein E-knockout (ApoE-/-) mice were negative and positive AS
      controls, respectively. A silica collar was placed around the right carotid
      artery of each mouse to induce AS development. All mice were fed a 24-week high
      fat diet, and investigated for AS lesions. We also compared the levels of blood
      lipid and glucose, serum tumor necrosis factor alpha (TNF-alpha), interleukin 6
      (IL-6), anti-nuclear antibody (ANA) and anti-double-stranded deoxyribonucleic
      acid (anti-dsDNA) antibody in Fas-/- mice with those in B6 or ApoE-/- mice. All
      ApoE-/- and 6 Fas-/- but no B6 mice showed atherogenesis in right carotid artery.
      The carotid plaque contains more collagen and less lipid in Fas-/- than ApoE-/-
      mice. The levels of blood glucose, serum TNF-alpha, IL-6, ANA, and anti-dsDNA
      antibody were significantly higher in Fas-/- mice than those in B6 mice, the
      levels of serum TNF-alpha and blood glucose were significantly higher and the
      level of blood lipid was significantly lower in Fas-/- mice than those in ApoE-/-
      mice. Therefore, carotid AS can develop in Fas-/- mice. Fas-/- mice display
      higher levels of serum IL-6, TNF-alpha, ANA, and anti-dsDNA than B6 mice, higher
      levels of serum TNF-alpha and blood glucose and lower level of blood lipid than
      ApoE-/- mice, and less lipid and more collagen in AS plaque than ApoE-/- mice.

PMID- 30235004
TI  - Unified platform for multimodal voxel-based analysis to evaluate tumour perfusion
      and diffusion characteristics before and after radiation treatment evaluated in
      metastatic brain cancer.
AB  - OBJECTIVE:: Early changes in tumour behaviour following stereotactic radiosurgery
      ) are potential biomarkers of response. To-date quantitative model-based measures
      of dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI parameters
      have shown widely variable findings, which may be attributable to variability in
      image acquisition, post-processing and analysis. Big data analytic approaches are
      needed for the automation of computationally intensive modelling calculations for
      every voxel, independent of observer interpretation. METHODS:: This unified
      platform is a voxel-based, multimodality architecture that brings complimentary
      solute transport processes such as perfusion and diffusion into a common
      framework. The methodology was tested on synthetic data and digital reference
      objects and consequently evaluated in patients who underwent volumetric DCE-CT,
      DCE-MRI and DWI-MRI scans before and after treatment. Three-dimensional
      pharmacokinetic parameter maps from both modalities were compared as well as the
      correlation between apparent diffusion coefficient (ADC) values and the
      extravascular, extracellular volume (Ve). Comparison of histogram parameters was
      done via Bland-Altman analysis, as well as Student's t-test and Pearson's
      correlation using two-sided analysis. RESULTS:: System testing on synthetic Tofts
      model data and digital reference objects recovered the ground truth parameters
      with mean relative percent error of 1.07 * 10-7  and 5.60 * 10-4 respectively.
      Direct voxel-to-voxel Pearson's analysis showed statistically significant
      correlations between CT and MR which peaked at Day 7 for Ktrans (R = 0.74, p <=
      0.0001). Statistically significant correlations were also present between ADC and
      Ve derived from both DCE-MRI and DCE-CT with highest median correlations found at
      Day 3 between median ADC and Ve,MRI values (R = 0.6, p < 0.01) The strongest
      correlation to DCE-CT measurements was found with DCE-MRI analysis using
      voxelwise T10 maps (R = 0.575, p < 0.001) instead of assigning a fixed T10 value.
      CONCLUSION:: The unified implementation of multiparametric transport modelling
      allowed for more robust and timely observer-independent data analytics. Utility
      of a common analysis platform has shown higher correlations between
      pharmacokinetic parameters obtained from different modalities than has previously
      been reported. ADVANCES IN KNOWLEDGE:: Utility of a common analysis platform has
      shown statistically higher correlations between pharmacokinetic parameters
      obtained from different modalities than has previously been reported.

PMID- 30235006
TI  - Reply to: Use of Masks in Cystic Fibrosis Patients.

PMID- 30235007
TI  - Anchoring and Adjustment in Uncertain Spatial Trajectory Prediction.
AB  - OBJECTIVE: The aim of this study was to explore the impact of prior information
      on spatial prediction and understanding of variability. BACKGROUND: In uncertain
      spatial prediction tasks, such as hurricane forecasting or planning search-and
      rescue operations, decision makers must consider the most likely case and the
      distribution of possible outcomes. Base performance on these tasks is varied (and
      in the case of understanding the distribution, often poor). Humans must update
      mental models and predictions with new information, sometimes under cognitive
      workload. METHOD: In a spatial-trajectory prediction task, participants were
      anchored on accurate or inaccurate information, or not anchored, regarding the
      future behavior of an object (both average behavior and the variability).
      Subsequently, they predicted an object's future location and estimated its
      likelihood at multiple locations. In a second experiment, participants repeated
      the process under varying levels of external cognitive workload. RESULTS:
      Anchoring influenced understanding of most likely predicted location, with fairly
      rapid adjustment following inaccurate anchors. Increasing workload resulted in
      decreased overall performance and an impact on the adjustment component of the
      task. Overconfidence was present in all conditions. CONCLUSION: Prior information
      exerted short-term influence on spatial predictions. Cognitive load impaired
      users' ability to effectively adjust to new information. Accurate graphical
      anchors did not improve user understanding of variability. APPLICATION: Prior
      briefings or forecasts about spatiotemporal trajectories affect decisions even in
      the face of initial contradictory information. To best support spatial prediction
      tasks, efforts also need to be made to separate extraneous load-causing tasks
      from the process of integrating new information. Implications are discussed.

PMID- 30235008
TI  - Detection of noncalcified breast cancer in patients with extremely dense breasts
      using digital breast tomosynthesis compared with full-field digital mammography.
AB  - OBJECTIVE:: To evaluate the tumour visibility and diagnostic performance of
      digital breast tomosynthesis (DBT) in patients with noncalcified T1 breast
      cancer. METHODS:: Medical records of 106 females with noncalcified T1 invasive
      breast cancer who underwent DBT and full-field digital mammography (FFDM) between
      January 2012 and December 2014 were retrospectively reviewed. To assess tumour
      visibility (score 1-3), all DBT and FFDM images were reviewed by two radiologists
      blinded to clinicopathological information. A reference standard was established
      by an unblinded consensus review of all images. Clinicopathological and imaging
      variables were analysed based on tumour visibility. After adding 159 negative
      controls, the diagnostic performance of DBT + FFDM was compared with that of
      FFDM. RESULTS:: The tumour visibility was significantly higher through DBT + FFDM
      (2.5 vs 1.8; p = 0.002) than FFDM alone. Breast composition was the independent
      variable for tumour visibility through DBT + FFDM (extremely dense; odds ratio,
      0.02; p < 0.001). Sensitivity (p = 0.642), specificity (p = 0.463), positive
      predictive value (p = 0.078), and negative-predictive value (p = 0.072) of DBT +
      FFDM were not significantly superior to those of FFDM in 55 females with
      extremely dense breast composition, whereas specificity (p = 0.002) and positive
      predictive value (p < 0.001) were significantly higher in 210 females with other
      breast compositions. CONCLUSION:: Addition of DBT to FFDM showed no significant
      increase in the tumour visibility and diagnostic performance in patients with
      noncalcified T1 cancer in extremely dense breasts. ADVANCES IN KNOWLEDGE::
      Addition of DBT to FFDM did not further improve the detection of noncalcified
      early breast cancers in females with extremely dense breasts.

PMID- 30235009
TI  - The Prognostic Significance of the Geriatric Nutritional Risk Index in Patients
      with Esophageal Squamous Cell Carcinoma.
AB  - The aim of this study was to investigate the impact of the geriatric nutritional
      risk index (GNRI) on the long-term outcomes in 137 esophageal squamous cell
      carcinoma (ESCC) patients who underwent curative esophagectomy. The GNRI was
      calculated from the serum albumin value and the body weight. The cutoff value of
      the GNRI was set at 98. A multivariate analysis was performed to identify
      prognostic factors for the overall survival (OS). The mean preoperative GNRI was
      99.9 +/- 7.8. Forty-five (32.8%) patients had a GNRI of <98. The GNRI was
      significantly associated with the tumor depth (p = 0.001), level of
      carcinoembryonic antigen (CEA; p = 0.009) and level of C-reactive protein (CRP; p
      = 0.028). The GRNI was significantly associated with the OS (p < 0.001). The
      multivariate analysis identified the GNRI as an independent predictor for the OS.
      Death due to EC was more frequent in the patients with a low GNRI than in the
      patients with a high GNRI (p = 0.004). Our results suggest that the GRNI is a
      simple and reliable predictor of the postoperative survival in ESCC patients. A
      low preoperative GNRI may indicate a higher risk of EC death.

PMID- 30235010
TI  - Prognostic Impact of Nutritional Status Assessed by the Controlling Nutritional
      Status (CONUT) Score in Patients with Surgically Treated Renal Cell Carcinoma.
AB  - PURPOSE: The prognostic role of the controlling nutritional status (CONUT) score
      in renal cell carcinoma (RCC) has not been evaluated. The aim of the current
      study was to clarify the prognostic significance of the CONUT score in Korean
      patients with surgically treated RCC. MATERIALS AND METHODS: A database of 1,881
      patients with surgically treated RCC from a multiinstitutional Korean
      collaboration between 1999 and 2015 was analyzed. The preoperative CONUT score
      was calculated from serum albumin, total cholesterol concentrations, and total
      lymphocyte count. Clinicopathological variables and survival rates were compared
      between the CONUT score groups. RESULTS: A high CONUT score was associated with
      older age, lower body mass index, lower preoperative prognostic nutritional
      index, and presence of diabetes or hypertension (each P < 0.001). Regarding
      pathologic features, a high CONUT score was associated with aggressive tumor
      characteristics including large tumor size, advanced stage, high nuclear grade,
      lymphovascular invasion, and sarcomatous differentiation (each P < 0.001).
      Multivariate Cox regression analysis indicated that a high CONUT score (>= 2) was
      an independent predictor of cancer-specific mortality (hazard ratio, 1.892; 95%
      CI: 1.118-3.201; P = 0.018). CONCLUSION: The CONUT score, an easily measurable
      immune-nutritional biomarker, may provide useful prognostic information in
      patients with surgically treated RCC.

PMID- 30235011
TI  - Oncogene Delta/Notch-Like EGF-Related Receptor Promotes Cell Proliferation,
      Invasion, and Migration in Hepatocellular Carcinoma and Predicts a Poor
      Prognosis.
AB  - PURPOSE: To determine the expression and function of Delta/Notch-like EGF-related
      receptor (DNER) in hepatocellular carcinoma (HCC). METHODS: The expression of
      DNER in 84 HCC tissue samples and matched adjacent noncancerous specimens, as
      well as HCC cells, were evaluated by quantitative real-time polymerase chain
      reaction (qRT-PCR) and western blotting. Survival analysis was evaluated using
      Kaplan-Meier method. For experiments in vitro, cell viability was measured by
      Cell Counting Kit-8 Assay and Colony Formation Assay. Furthermore, cell invasion
      and migration assays were performed with Transwell Assay. RESULTS: The results
      showed that DNER was overexpressed in the tissues and cell lines of HCC (all, p <
      0.05), and the upregulated expression of DNER was significantly correlated with
      advanced pathologic stage (p = 0.013) and pathologic-M1 (p = 0.012) in HCC
      patients. Survival analysis revealed that patients with high DNER levels had
      worse overall survival (OS) than those with low DNER levels (p = 0.004). More
      importantly, DNER could be an independent predictor of prognosis for OS (HR =
      2.582, 95% CI 1.239-5.380, p = 0.011). In vitro, knockdown of DNER significantly
      suppressed cell proliferation, colony formation, cell invasion, and cell
      migration in HepG2 cells. Moreover, inhibition of DNER inactivated PI3K/AKT
      signaling pathway by downregulating the expression of p-PI3K, p-AKT, and p-70s6k.
      CONCLUSIONS: Taken together, DNER could promote proliferation, migration, and
      invasion of HCC cells by regulating the activation of PI3K/AKT pathway, and it
      might act as a potential prognostic biomarker for HCC.

PMID- 30235012
TI  - Prospective Study on Body Composition, Energy Balance and Biological Factors
      Changes in Post-menopausal Women with Breast Cancer Receiving Adjuvant
      Chemotherapy Including Taxanes.
AB  - In breast cancer patients, weight and fat mass changes observed after
      chemotherapy have been related to poor prognosis but some recent works using
      modern chemotherapy failed to find this correlation with weight gain. In this
      study, the extent of changes in weight and body composition (DEXA, impedance) was
      characterized until six months after current chemotherapy, in 50 post-menopausal
      women with breast cancer. The evolution of factors contributing to the energy
      balance and some biological factors were also described. During chemotherapy, 20%
      of women lost weight due to both fat (-13.1% +/- 10.3) and lean soft tissue mass
      loss (-3.6% +/- 4.6). Twenty percent of women gained weight. No significant fat
      mass gain was observed in these women but significant water gain was highlighted.
      Six months later, women who gained weight presented a gain in fat mass (15.4% +/-
      19.0), especially in the abdominal region. Age and initial BMI were negatively
      correlated with fat mass in multivariate analyzes (r = 0.486, P = 0.0030). No
      significant variation of the glucose homeostasis, triglycerides, and HDL
      Cholesterol was found six months after chemotherapy. These results do not suggest
      major adverse metabolic disturbances six months after modern chemotherapy and
      only a mild fat mass gain was observed in women who gained weight.

PMID- 30235013
TI  - Serum Albumin at Diagnosis is an Independent Predictor of Early Mortality in
      Veteran Patients with Esophageal Cancer.
AB  - AIMS: To identify independent factors that could predict mortality within 6
      months in a cohort of patients with esophageal cancer. METHODS: Esophageal cancer
      patients were grouped into early (<=6 months, n = 41) and late (>6 months, n =
      81) mortality groups. 52 variables were analyzed by univariable analysis (UA). A
      multivariable (MVA) regression model was created to identify predictors of early
      mortality. RESULTS: When comparing early and late mortality groups, there was no
      difference in age, BMI, race, histology, or anatomic location between the two
      groups. UA demonstrated that the early mortality group had a lower mean albumin
      level (3.3 +/- 0.1 g/dl vs. 3.8 +/- 0.1 g/dl; P < 0.001), poorer ECOG performance
      status (1.9 +/- 0.2 vs. 1.1 +/- 0.1, P = 0.02), higher WBC count (9.6 +/- 0.7
      K/uL vs. 8.2 +/- 0.3 K/uL, P = 0.04), and were less likely to receive surgery
      (2.4% vs. 22.2%; P = 0.003), neoadjuvant treatment (4.9% vs. 28.4%; P = 0.009)
      and definitive chemoradiation (7.3% vs. 27.2%; P = 0.01). MVA revealed that only
      low albumin at diagnosis was an independent predictor of survival (P = 0.016).
      CONCLUSION: Albumin level at diagnosis is an independent predictor of early
      mortality and might be used with other variables to provide prognostic
      information for patients and to guide treatment.

PMID- 30235014
TI  - Behavioral Adaptations to Lane Keeping Systems: Effects of Exposure and
      Withdrawal.
AB  - OBJECTIVE: A driving simulator study was conducted to evaluate the longitudinal
      effects of an intervention and withdrawal of a lane keeping system on driving
      performance and cognitive workload. BACKGROUND: Autonomous vehicle systems are
      being implemented into the vehicle fleet. However, limited research exists in
      understanding the carryover effects of long-term exposure. METHODS: Forty-eight
      participants (30 treatment, 18 control) completed eight drives across three
      separate days in a driving simulator. The treatment group had an intervention and
      withdrawal of a lane keeping system. Changes in driving performance (standard
      deviation of lateral position [SDLP] and mean time to collision [TTC]) and
      cognitive workload (response time and miss rate to a detection response task)
      were modeled using mixed effects linear and negative binomial regression.
      RESULTS: Drivers exposed to the lane keeping system had an increase in SDLP after
      the system was withdrawn relative to their baseline. Drivers with lane keeping
      had decreased mean TTC during and after system withdrawal compared with manual
      drivers. There was an increase in cognitive workload when the lane keeping system
      was withdrawn relative to when the system was engaged. CONCLUSION: Behavioral
      adaptations in driving performance and cognitive workload were present during
      automation and persisted after the automation was withdrawn. APPLICATION: The
      findings of this research emphasize the importance to consider the effects of
      skill atrophy and misplaced trust due to semi-autonomous vehicle systems.
      Designers and policymakers can utilize this for system alerts and training.

PMID- 30235015
TI  - Autoimmune epilepsy: Findings on MRI and FDG-PET.
AB  - Autoimmune epilepsy (AE) is becoming increasingly recognized as a potentially
      reversible cause of frequent or medically intractable seizures and cognitive
      deterioration. We describe various presentations of autoimmune encephalopathy
      which have specifically presented with seizure and describe reported imaging
      findings. This is organized as a review of the more common autoantibodies which
      can specifically precipitate seizure according to the intracellular or
      extracellular location of the targeted antigen. For each antibody, we illustrate
      their pathophysiology, characteristic clinical presentations with typical
      effective treatments and prognoses and imaging findings on MRI and PET/CT exams.
      Parenchymal involvement is variable with the limbic structures typically
      affected; however, non-limbic cortex, cerebellum, brainstem and basal ganglia can
      also be involved. In the acute setting, affected regions typically demonstrate T2
      hyperintensity with mild mass effect from edema and increased 18F-FDG uptake.
      Chronically involved parenchyma will often undergo atrophy and demonstrate
      decreased metabolism; mesial temporal sclerosis (MTS) is often the end result
      when the limbic system is involved. Without treatment, long term effects from AE
      range from ongoing cognitive dysfunction and refractory seizures to death.
      Familiarity with AE may prompt appropriate antibody screening, particularly in
      cases of refractory seizure disorders. Early investigation and proper management
      of AE cases may help to prevent parenchymal and neurologic deterioration in these
      patients.

PMID- 30235016
TI  - Western Dietary Pattern, But not Mediterranean Dietary Pattern, Increases the
      Risk of Prostate Cancer.
AB  - BACKGROUND AND AIM: Prostate cancer is the most common cancer among men. Several
      studies have investigated the effects of dietary patterns on prostate cancer
      risk, but this topic is still a matter of debate. This study aimed to examine the
      association between dietary patterns and prostate cancer risk. METHODS: In a case
      control study, 60 newly diagnosed prostate cancer cases and 60 hospital-based
      controls were selected from two main hospitals of Shiraz, Iran. Data on dietary
      intakes, anthropometric features, and demographic characteristics were collected.
      To determine the dietary patterns factor analysis, and to estimate the odds
      ratios (ORs), multivariable logistic regression was performed. RESULTS: Two major
      dietary patterns were identified: Western dietary (WD) pattern and Mediterranean
      dietary (MD) pattern. After adjusting for potential confounders, men who had
      higher scores for WD pattern (above the median) were more likely to have prostate
      cancer (OR = 5.15; 95% CI (1.44-18.47); P = 0.01) compared with men who had lower
      scores. A nonsignificant inverse association was found for MD pattern (OR = 0.62;
      95% CI (0.22-1.77); P = 0.37). CONCLUSIONS: Our findings suggest that WD pattern
      may increase the risk of prostate cancer and the beneficial effects of MD pattern
      on prostate cancer risk need further research.

PMID- 30235017
TI  - Dietary Inflammatory Index and Odds of Breast Cancer in a Case-Control Study from
      Iran.
AB  - Chronic inflammation is implicated in breast cancer (BrCa) development; however,
      studies on the association of the inflammatory potential of diet and breast
      cancer have produced conflicting results. With this as background, we
      investigated the association between dietary inflammatory index (DII(r)) scores
      and BrCa risk in an Iranian case-control study. In this study, 136 newly
      diagnosed breast cancer patients and 272 hospitalized controls were recruited
      using convenience sampling. DII scores were computed from dietary intake data
      collected through a validated food frequency questionnaire (FFQ). Adjusted odds
      ratios (OR) and 95% confidence intervals (CI) for the association between the DII
      and BrCa risk were estimated by logistic regression. After controlling for
      multiple potential confounders, a significantly increased BrCa odds was observed
      in the highest quartile of DII score compared to the lowest quartile (ORquartile
      4 vs. 1 = 2.64, 95% CI: 1.12-6.25; Ptrend = 0.01). In subanalysis based on
      menopausal status, a positive association was observed between the DII and BrCa
      risk among premenopausal women (ORquartile 4 vs. 1 = 5.51, 95% CI: 1.45-20.93;
      Ptrend = 0.005); however, no association was detected in postmenopausal women.
      Our findings suggest that more proinflammatory diets, indicated by higher DII
      scores, may increase the odds of BrCa, especially among premenopausal women.

PMID- 30235019
TI  - A nursing perspective on rare diseases: mesothelioma.

PMID- 30235018
TI  - Low Plasma Omega-3 Fatty Acid Levels May Predict Inferior Prognosis in Untreated
      Diffuse Large B-Cell Lymphoma: A New Modifiable Dietary Biomarker?
AB  - Dietary factors that may reduce the risk of relapse or prolong remission are an
      area of interest for patients with cancer. There is little data on the role of
      omega-3 fatty acids (n-3 FA) in patients diagnosed with lymphoma. This pilot
      biomarker study evaluated the prognostic significance of n-3 FA levels in
      patients with diffuse large B-cell lymphoma (DLBCL). In this analysis, low n-3 FA
      may be associated with inferior event free survival at 24 months in this disease.
      Larger studies are needed to confirm this association and could provide the basis
      for prospective investigation of whether modifying n-3 levels with diet may
      improve outcome in lymphoma.

PMID- 30235020
TI  - Oncology Nurse of the Year, Runner-up 2018.

PMID- 30235021
TI  - Reducing the risks of surgical site infection: the importance of the
      multidisciplinary team.
AB  - Surgical site infection (SSI), which can range from superficial infection to life
      threatening problems, puts extra strain on healthcare resources and can have a
      significant impact on patient quality of life. The majority of SSIs are
      preventable, with different members of the multidisciplinary team (MDT) playing
      their part at every stage of the patient journey from preoperative assessment to
      post-discharge follow up. Effective communication and cooperation between members
      of the MDT is key. This article provides an overview of the input at different
      stages along the patient journey.

PMID- 30235022
TI  - Transformational leadership and ethical leadership: their significance in the
      mental healthcare system.
AB  - This article critically compares transformational leadership and ethical
      leadership. It discusses the differences, similarities, weaknesses and strengths
      of the two styles. The importance of strong leadership in meeting an array of
      challenges and changes occurring in the NHS is highlighted. The article explores
      the influence of transformational and ethical leadership styles on the role of
      nurse leaders, particularly those in mental health, and also the influence of
      emotional intelligence in leadership. Over the last five decades, there has been
      a transformation in mental health, but more needs to be done to ensure everyone
      can access high-quality care when they need it. Transformational leadership
      remains important in such an ever-changing healthcare environment, but ethical
      behaviour should be its base.

PMID- 30235023
TI  - The 'silly season'.

PMID- 30235024
TI  - Frozen food dangers.

PMID- 30235025
TI  - Oxygen therapy in adult patients. Part 2: promoting safe and effective practice
      in patients' care and management.
AB  - The assessment, care and management of patients requiring oxygen therapy are key
      aspects of a nurse's role. Although oxygen therapy is an important treatment for
      many clinical conditions, it carries risks and complications; therefore, nurses
      and other health professionals have a responsibility to ensure safe and effective
      practice along with maintaining and developing their knowledge and skills in this
      therapy. The relevant aspects of physiology and pathophysiology were explored and
      discussed in part one of this article ( Rolfe and Paul, 2018 ). The aims of the
      second part are to discuss: (1) the indications for oxygen therapy; (2) the
      principles of assessment, care and management of adult patients requiring oxygen
      therapy; and (3) recommendations for the safe and effective use of oxygen
      devices, along with the potential complications.

PMID- 30235026
TI  - Designing an education programme to improve quality of life for cancer survivors:
      a systematic review.
AB  - Health and wellbeing education programmes, as part of the recovery package, are
      now recommended for all cancer patients on completion of treatment. There is
      limited evidence to determine whether such programmes improve the quality of life
      (QoL) for cancer survivors. The purpose of the systematic review was to
      synthesise the available research and provide recommendations for practice and
      education programme delivery. A critical appraisal and narrative synthesis of
      eligible randomised controlled trials showed that there was a small mean
      percentage difference in reported QoL for cancer survivors who participated in an
      education programme (8%) over those who received usual care alone (7%). Cancer
      site specific programmes are recommended over generic programmes. The optimum
      time frame for programme delivery is between 3 and 12 months following treatment.
      Various methods of programme delivery are effective, including face-to-face group
      sessions and self-directed web-based programmes.

PMID- 30235027
TI  - A protocol to improve the sharing of concerns about health care.
AB  - Emeritus Professor Alan Glasper, from the University of Southampton, discusses
      the Emerging Concerns Protocol, designed to help health and social care
      institutions and regulators share concerns more effectively.

PMID- 30235028
TI  - Ensuring safe, sustainable and productive staffing.
AB  - Sam Foster, Chief Nurse, Oxford University Hospitals, considers the impact of the
      staffing crisis and guidance produced for the National Quality Board around
      changes in staffing and skill mix.

PMID- 30235029
TI  - Belonging and loss in the transition to newly qualified nursing.
AB  - Duncan Hamilton, at the time of writing a final year adult nursing student at the
      University of Surrey, considers an unexpected sense of melancholy at the end of
      his course.

PMID- 30235030
TI  - A view from the other side of the Atlantic.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, discusses a recently published patient safety report from the USA
      within the context of global initiatives to improve the safety of care.

PMID- 30235031
TI  - Patient surveys highlight areas for improving cancer care.

PMID- 30235032
TI  - Ambulatory approach to cancer care. Part 1: the patient experience.
AB  - Ambulatory care (AC) is an approach within which inpatient chemotherapy regimens
      and supportive care are delivered in an outpatient service. Patients receive
      their treatments and supportive care daily in AC and stay at a nearby hotel or
      their home, rather than in an inpatient bed. A systematic literature search found
      a growing amount of literature on AC and the specific regimens used. However,
      little was found on AC with regard to the patient experience, safety, the
      benefits and challenges of running an AC service. This series of three articles
      is based on the authors' experiences of working within an AC service at a major
      London teaching hospital. The authors discuss the approach and explore how it can
      improve the patient experience. They look at the roles of the multidisciplinary
      team and their part in patient safety, and the benefits, challenges and cost
      considerations of an AC service.

PMID- 30235033
TI  - Supreme Court ruling on the withdrawal of life-sustaining nutrition.
AB  - Richard Griffith, Senior Lecturer in Health Law at Swansea University, considers
      the Supreme Court's decision on the need to bring cases concerning the
      withdrawing of clinically assisted nutrition to court.

PMID- 30235035
TI  - CPD: a priority for nurse retention?
AB  - Janet Scammell, Associate Professor (Nursing), Bournemouth University, discusses
      whether prioritising the provision of continuing professional development would
      help improve nurse retention levels.

PMID- 30235034
TI  - Patient preferences for involvement in health service development.
AB  - BACKGROUND:: patient involvement in the design, planning and delivery of health
      services is acknowledged to be a local and national priority. AIMS:: to improve
      service quality through a quality improvement initiative to explore patient
      preferences for involvement in health services design, planning and delivery.
      METHODS:: a questionnaire was developed to: assess patient preferences for
      involvement in hospital service development; and explore differences in responses
      between patient subgroups. FINDINGS:: 162 patients were recruited. Most were
      positive about being engaged in all service developments, not just those used
      personally. Involvement through questionnaires with infrequent email
      communication was favoured over attendance at public meetings. Time was a greater
      barrier to being involved than distance or remuneration. Conclusion' Patients
      valued involvement in health service development, but finding free time during
      working hours was difficult. There were no differences in preferences for
      involvement between subgroups defined by gender, ethnicity, home situation or
      health.

PMID- 30235036
TI  - What is diabulimia and what are the implications for practice?
AB  - Diabulimia has become a common term used to describe a condition when a person
      with type 1 diabetes has an eating disorder. The individual may omit or restrict
      their insulin dose to lose/control weight. Evidence suggests that as many as 20%
      of women with type 1 diabetes may have this condition. The serious acute and long
      term complications of hyperglycaemia are well documented. Detection of this
      condition is challenging and health professionals need to be vigilant in
      assessing reasons for variable glycaemic control and weight changes. Management
      requires a collaborative response from the specialist diabetes team in
      conjunction with the mental health team. Nurses must ensure that they are aware
      that the condition may be possible in all patients with type 1 diabetes but
      especially younger female patients. These patients require timely intervention to
      prevent any severe acute or long-term complications.

PMID- 30235037
TI  - Newborn Screening and Health Communications.

PMID- 30235038
TI  - Mutational Screening of GLI3, SHH, and SHH ZRS in 78 Chinese Children with
      Nonsyndromic Polydactyly.
AB  - BACKGROUND: Polydactyly is one of the most common congenital limb abnormalities.
      Our objective was to identify the genetic causes of non-syndromic polydactyly in
      78 Chinese children. MATERIALS AND METHODS: Genomic DNA was isolated from 78
      independent nonsyndromic polydactyly patients, of whom 71 had preaxial
      polydactyly (PPD), six had postaxial polydactyly (PAP), and one showed combined
      PPD1 and PAP-A/B. The coding areas and exon/intron boundaries of the GLI3 and SHH
      genes and the genomic region of SHH ZRS were amplified by polymerase chain
      reaction and sequenced. RESULTS: The patient with combined PPD1 and PAP-A/B
      (subject DUO36) exhibited a heterozygous nonsense mutation in chr7: 42004164G>A
      (ENST00000395925, c.4507C>T, p.Gln1503Stop ) of the GLI3 gene that has not been
      previously recorded. We did not detect any mutations in GLI3, SHH, or SHH ZRS in
      the other 77 nonsyndromic polydactyly patients. CONCLUSION: The novel mutation in
      GLI3 c.4507C>T is likely one of the causes of the PAP and PPD1 of subject DUO36.
      This important finding should facilitate the optimization of genetic testing for
      nonsyndromic polydactyly.

PMID- 30235039
TI  - Genetic Testing of a Large Consanguineous Pakistani Family Affected with
      Mucolipidosis III Gamma Through Next-Generation Sequencing.
AB  - BACKGROUND: Mucolipidosis III gamma (MLIIIgamma) is a rare autosomal recessive
      disorder characterized by radiographic evidence of mild-to-moderate dysostosis
      multiplex, progressive joint stiffness and pain, scoliosis, and normal to mildly
      impaired cognitive development. Cardiac valve involvement and respiratory
      complications can be significant. MLIIIgamma is caused by mutations in the GNPTG,
      which encodes the gamma subunit of the enzyme N-acetylglucosamine-1
      phosphotransferase. OBJECTIVE: Clinical and genetic study of seven individuals of
      a consanguineous Pakistani family affected with mucolipidosis phenotype who never
      pursued medical care. METHODS: Genome-wide homozygosity mapping was performed
      using Affymetrix Human SNP Array 6.0 followed by whole exome and Sanger
      sequencing. RESULTS: The affected individuals showed characteristic clinical
      features of MLIIIgamma. Whole-genome single nucleotide polymorphism genotyping
      identified a region of homozygosity shared by affected individuals of the family
      on chromosome 16p13.3. Whole exome sequencing identified a novel 4-bp deletion in
      the GNPTG segregating in the family in agreement with autosomal recessive
      pattern. CONCLUSIONS: We identified a novel mutation in the GNPTG gene as the
      underlying cause of MLIIIgamma in a Pakistani family. This study supports the
      role of next-generation sequencing technologies for the molecular diagnosis of
      rare inherited disorders.

PMID- 30235040
TI  - Use of the logic model to develop and implement an interprofessional module for
      undergraduate healthcare students at a University in South Africa: A study
      protocol.
AB  - Interprofessional education and collaborative practice, supported by the World
      Health Organisation and the local Health Professions Council is not fully
      established at all universities and for all health professions in South Africa
      (HPCSA, 2014). In this study protocol, the logic model is proposed as a framework
      for the development of a module for final year healthcare students. The logic
      model will guide planning and implementation following the steps of situational
      analysis, input and processes, output and outcome. A community of practice will
      develop the module. Large-scale buy-in from management, faculty and students is
      required for successful implementation and sustainability.

PMID- 30235041
TI  - Topical brimonidine-assisted laser treatment for the prevention of therapy
      related erythema and hyperpigmentation.
AB  - Postinflammatory hyperpigmentation (PIH) and erythema are the most common adverse
      effects associated with laser treatment, particularly in dark-skinned
      individuals. Several methods have been used to prevent or minimize these adverse
      effects; however, to date, no definitive precautions/strategies are known to
      prevent post-laser PIH and erythema. We investigated whether the topical
      application of the alpha-adrenergic receptor agonist brimonidine could reduce
      laser treatment-related complications such as erythema and PIH.

PMID- 30235042
TI  - Effectiveness of Intraductal Meibomian Gland Probing in Addition to the
      Conventional Treatment in Patients with Obstructive Meibomian Gland Dysfunction.
AB  - PURPOSE: To evaluate the effectiveness of intraductal meibomian gland probing in
      addition to conventional treatment for the management of obstructive meibomian
      gland dysfunction (O-MGD). METHODS: Totally, 40 patients were divided into two
      groups to receive either conventional treatment alone (group 1: 40 eyes of 20
      patients) or conventional treatment plus probing (group 2: 40 eyes of 20
      patients). The ocular surface disease index score, Schirmer 1 test, tear film
      break-up time, Oxford grading of ocular surface, meibum expressibility, and
      quality scores were evaluated baseline and compared with the end of treatment
      (day 30 and day 90). RESULTS: There was no significant difference in baseline
      scores between groups (All p > 0.05). All scores demonstrated significantly
      improvement from baseline in both group, and it was faster in group 2 (All p <
      0.05). CONCLUSION: This study showed that intraductal meibomian gland probing
      seems to provide rapid symptom relief and clinical improvement for patients with
      O-MGD.

PMID- 30235043
TI  - Evaluation of a Breastfeeding App in Rural Australia: Prospective Cohort Study.
AB  - BACKGROUND: New mothers often need support to establish and maintain
      breastfeeding, and rural women may find it difficult to access breastfeeding
      resources locally. There are many smartphone applications for breastfeeding
      mothers; however, very few have been developed by health professionals. We
      evaluated a smartphone application, Breastfeeding Solutions, developed by U.S.
      IBCLC Nancy Mohrbacher. Research aims: The aims were (a) to explore usability of
      the application among rural Australian breastfeeding women and (b) to describe
      participants' infant feeding outcomes compared with the general population.
      METHODS: A prospective longitudinal self-report survey design was used. Data were
      collected via online questionnaires at baseline and at 3 and 6 months from a
      convenience sample of new mothers. The setting was southwest Victoria, Australia,
      from 2016 to 2017. Descriptive statistics were used to answer research aims.
      RESULTS: Of the initial 46 participants who received the app, 63% ( n = 29)
      completed surveys at 3 and 6 months. Usability was assessed at 3 months: 93.5% of
      participants (29 of 31) rated the application favorably, whereas 96.8% (30 of 31)
      found the application helpful and 87.1% (27 of 31) would recommend it to other
      mothers. At the 6-month survey, 79% of participants ( n = 23) were breastfeeding;
      10% ( n = 3) had stopped breastfeeding during the first 3 months. The local
      breastfeeding rate at 6 months was approximately 50% according to routinely
      collected data; however, we cannot infer that the application was responsible for
      the difference. CONCLUSION: The smartphone application was acceptable to
      breastfeeding women in an Australian rural setting. Further evaluation using a
      user-centered design could improve rural postpartum women's access to reliable,
      evidence-based information.

PMID- 30235044
TI  - Positive Distraction in Pediatric Healthcare Waiting Spaces: Sharing Play Not
      Germs through Inclusive, Hands-Free Interactive Media.
AB  - PURPOSE: To investigate the value of shared opportunities for positive
      distraction in pediatric healthcare environments. METHODS: Self-selected
      activities of 271 young people (5-19 years) with diverse neurodevelopmental
      conditions were observed in an ambulatory pediatric rehabilitation clinic. Shared
      opportunities included hands-free media (nature video or interactive media) and
      an aquarium. Anxiety was self-reported on the State Trait Anxiety Scale upon
      arrival and after 10 minutes in the waiting space. RESULTS: Young people engaged
      more with shared opportunities for distraction (n = 170/271) than personal items
      brought from home (n = 119/271), p = 0.02. Personal electronic devices were used
      by 67 young people, but did not positively impact anxiety. Interactive media and
      the aquarium significantly reduced anxiety (p < 0.04) while the nature video
      appeared to increase anxiety (p = 0.036). Age influenced activity preference and
      anxiety. Shared, hands-free interactive media engaged individuals of diverse age
      and mobility. CONCLUSION: Shared opportunities for positive distraction in
      healthcare facilities are valuable, particularly hands-free interactive media.

PMID- 30235045
TI  - NeurHistAlert 24.

PMID- 30235046
TI  - Broad protective immune responses elicited by bacterium-like particle-based
      intranasal pneumococcal particle vaccine displaying PspA2 and PspA4 fragments.
AB  - Streptococcus pneumoniae is an infectious pathogen mainly infecting host bodies
      through the respiratory system. An effective pneumococcal vaccine would be
      targeted to the mucosa and provide not only protection against invasive infection
      but also against colonization in the respiratory system. In the present work, we
      applied bacterium-like particles (BLPs) as an adjuvant for the development of a
      PspA mucosal vaccine, in which the PspA protein was displayed on the surface of
      BLPs. Intranasal immunization with the PspA-BLP pneumococcal vaccine, comprised
      of PspA2 from pneumococcal family 1 and PspA4 from pneumococcal family 2, not
      only induced a high level of serum IgG antibodies but also a high level of
      mucosal SIgA antibodies. Analysis of binding of serum antibodies to intact
      bacteria showed a broad coverage of binding to pneumococcal strains expressing
      PspA from clade 1 to 5. Immunization with the PspA-BLP vaccine conferred
      protection against fatal intranasal challenge with both PspA family 1 and family
      2 pneumococcal strains regardless of serotype. Therefore, the PspA-BLP
      pneumococcal vaccine was demonstrated to be a promising strategy for mucosal
      immunization to enhance both systemic and mucosal immune responses.

PMID- 30235047
TI  - Possible inhibition of Arabidopsis VIP1-mediated mechanosensory signaling by
      streptomycin.
AB  - VIP1 (VIRE2-INTERACTING PROTEIN 1) and its close homologues are Arabidopsis
      thaliana bZIP proteins regulating stress responses and root tropisms. They are
      present in the cytoplasm under steady conditions, but transiently accumulate in
      the nucleus when cells are exposed to mechanical stress such as hypo-osmotic
      stress and touch. This pattern of changes in subcellular localization is unique
      to VIP1 and its close homologues, and can be useful to further characterize
      mechanical stress signaling in plants. A recent study showed that calcium
      signaling regulates this pattern of subcellular localization. Here, we show that
      a possible calcium channel inhibitor, streptomycin, also inhibits the nuclear
      accumulation of VIP1. Candidates for the specific regulators of the
      mechanosensitive calcium signaling are further discussed.

PMID- 30235048
TI  - Parenting Behaviors after Moderate - Severe Traumatic Injury in Early Childhood.
AB  - PURPOSE: Examine the impact of traumatic brain injury (TBI) on parenting behavior
      over time. METHOD: Included 206 children (3-7 years old) with moderate to severe
      TBI or orthopedic injury, using a prospective longitudinal cohort study design.
      Assessments completed at baseline, 6-months, 12-months, 18-months, 3.5 years, and
      6.8 years after injury. Dependent variables included authoritative, permissive,
      and authoritarian parenting. RESULTS: Injury characteristics had limited impact
      on parenting behaviors over time. Levels of authoritative parenting remained
      stable over time; however, levels of warmth and involvement declined over time
      for those with TBI. Levels of permissive and authoritarian parenting declined for
      all participants by 3.5 years post injury. SES and stressors impacted parenting
      behaviors. CONCLUSIONS: While there was limited effect of TBI on parenting
      behavior over time, it remains unclear how individuals respond to these parenting
      behaviors years after injury. Clinicians should monitor family and parenting
      behaviors to foster an environment to promote positive recovery.

PMID- 30235050
TI  - Eyes on New Product Development.

PMID- 30235049
TI  - Influence of testosterone substitution on glycemic control and endothelial
      markers in men with newly diagnosed functional hypogonadism and type 2 diabetes
      mellitus: a randomized controlled trial.
AB  - Effects of testosterone (T) on the cardiovascular system of men remain
      controversial. The impact of T-replacement therapy (TRT) in men with functional
      hypogonadism and type 2 diabetes mellitus (T2DM) has to be elucidated. This study
      included 80 men (mean age 51.5 +/- 6.3 years) with newly diagnosed T2DM
      (according to ADA criteria) and functional hypogonadism (according to EAU
      criteria). Randomization: Group1 (n = 40): TRT using 1%-transdermal T-gel (50
      mg/day), Group2 (n = 40) no TRT (controls). Dietary treatment applied to both.
      Parameters at baseline/after 9 months: anthropometric parameters, lipids and
      indicators of carbohydrate metabolism (fasting glucose, insulin, HbA1c, HOMA-IR),
      markers of adipose tissue and EnD (leptin, resistin, p- and e-selectin, ICAM- 1,
      VCAM- 1 and CRP). ANCOVA for repeated measurements revealed TRT to cause a
      significant decrease in waist circumference (WC), HOMA-IR and HbA1c vs controls
      (p < .001, p = .002, p = .004, respectively). Leptin declined in subjects
      receiving TRT vs controls (p = .04). Concentrations of resistin, ICAM-1, p
      selectin and CRP decreased significantly vs controls (all p < .001); no effects
      for e-selectin and VCAM-1. Advanced age attenuated effects, higher delta
      testosterone levels augmented effects. Decrement of WC was related to decreasing
      markers of adipose tissue secretion/EnD. TRT in men with functional hypogonadism
      and T2DM improved carbohydrate metabolism and markers of endothelial dysfunction.

PMID- 30235052
TI  - A license to cure.

PMID- 30235051
TI  - Guarding against dispassion for doctors in the NHS.
AB  - Compassion has always been a vital component of healthcare anywhere in the world.
      With numerous definitions in a variety of contexts, it cannot simply be
      prescribed, measured or given in a bottle. When our patients are ill, great
      attention is paid to the verbal and non-verbal communication presented by a
      doctor and the manner in which they are delivered. However, with an ever-growing
      demand on the NHS workforce, numerous patient surveys across the UK have accused
      doctors for lacking compassion in their practice, amid the strains of their
      modern-day commitments. The concept of being caring to our patients is
      highlighted from the first walks of medical school or indeed any healthcare
      professional's training programme, meaning that patients will always be our prime
      audience for compassion. Yet, so often in medical training, it is emphasised how
      important it is to demonstrate a personal detachment between oneself and the
      patient and not to get too emotionally involved. So despite numerous challenges,
      how do we find the correct balance to optimise our day-to-day service and stay
      sensitive to the needs of our patients? This article reflects upon compassion
      from multiple perspectives in the NHS pertinent to doctors of all settings and
      experience levels, exploring the barriers, internal conflicts and facilitators of
      its delivery. We examine the objective evidence of measures that have been put in
      place to overcome these challenges and summarise key considerations to optimise
      the enablement of a workforce to deliver compassion at universally higher
      standards in future practice.

PMID- 30235053
TI  - An evaluation of a safety improvement intervention in care homes in England: a
      participatory qualitative study.
AB  - OBJECTIVE: A growing proportion of older people live in care homes and are at
      high risk of preventable harm. This study describes a participatory qualitative
      evaluation of a complex safety improvement intervention, comprising training,
      performance measurement and culture-change elements, on the safety of care
      provided for residents. DESIGN: A participatory qualitative study. SETTING:
      Ninety care homes in one geographical locality in southern England. PARTICIPANTS:
      A purposeful sample of care home managers, front-line staff, residents, quality
      improvement facilitators and trainers, local government and health service
      commissioners, and an embedded researcher. MAIN OUTCOME MEASURES: Changes in care
      home culture and work processes, assessed using documentary analysis, interviews,
      observations and surveys and analysed using a framework-based thematic approach.
      RESULTS: Participation in the programme appears to have led to changes in the
      value that staff place on resident safety and to changes in their working
      practices, in particular in relation to their desire to proactively manage
      resident risk and their willingness to use data to examine established practice.
      The results suggest that there is a high level of commitment among care home
      staff to address the problem of preventable harm. Mobilisation of this commitment
      appears to benefit from external facilitation and the introduction of new methods
      and tools. CONCLUSIONS: An evidence-based approach to reducing preventable harm
      in care homes, comprising an intervention with both technical and social
      components, can lead to changes in staff priorities and practices which have the
      potential to improve outcomes for people who live in care homes.

PMID- 30235054
TI  - IBFAN News Brief: Protecting Breastfeeding at the World Health Assembly May 2018.

PMID- 30235055
TI  - Intraosseous Administration of Tissue Plasminogen Activator on a Mobile Stroke
      Unit.
AB  - OBJECTIVE: Mobile stroke units offer improved time to administration of
      thrombolytics for ischemic stroke patients. Acquisition of intravenous (IV)
      access, however, can be challenging in the prehospital environment leading to
      treatment delays. Intraosseous (IO) access is commonly used in the prehospital
      setting for a variety of conditions and may serve as a viable means for tPA
      (tissue plasminogen activator) administration. METHODS/RESULTS: We describe 3
      cases in which tPA was administered via IO access on a mobile stroke unit as part
      of the Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared
      to Standard Management by Emergency Medical Services (BEST-MSU) trial.
      CONCLUSION: No adverse events were observed in the process of obtaining IO access
      or administering tPA.

PMID- 30235057
TI  - Special focus on challenges and opportunities for the development and use of
      vaccines in Africa.
AB  - Immunization of children against vaccine-preventable diseases is one of the most
      cost-effective and potentially equitable public health interventions.
      Nevertheless, approximately 19.9 million of the world's annual birth cohort are
      either under-immunized or have not been vaccinated at all. Understanding the
      factors contributing to under-immunization in settinsg such as sub-Saharan Africa
      which bears a disproportionate burden of vaccine preventable diseases is key to
      unlocking the full potential that vaccines offer in reducing under-5 morbidity
      and mortality. The series or articles in this issue of the Journal, mainly
      through systematic analysis of District Health Surveillance data bases from 35
      countries, highlight the challenges faced in improving vaccination coverage rates
      in sub-Saharan Africa which has stagnated at approximately 72% for completion of
      the primary series of infant vaccines over the past decade. The reasons for under
      immunization of children is sub-Saharan Africa is identified to be multi
      factorial and may differ between and within countries. This highlights the need
      for country-specific, possibly at a district or sub-regional level, interrogation
      of factors contributing to under-immunization of children, to work toward
      providing Universal Health Coverage as envisioned in the Sustainable Development
      Goals.

PMID- 30235056
TI  - Measuring childhood vaccination acceptance of mother in Zhejiang province, East
      China.
AB  - BACKGROUND: The aim of this study was to evaluate the vaccine hesitancy among
      mothers and examine risk factors associated with mother's intention to
      vaccination in Zhejiang province. METHODS: A provincial sample of mothers of
      children aged 24-35 months was surveyed (N = 770) in August, 2017. Demographic
      information, perception on the past childhood vaccination, knowledge on
      vaccination, information searches and needs, trust in different institutions on
      vaccination were collected. Based on the theory of planned behaviour (TPB),
      attitudes toward vaccination, perceived social support, perceived behavioural
      control as well as mothers' intention to immunize their child were constructed.
      Descriptive statistics were generated for all variables. Univariate and
      multivariate analyses were performed to identify differences between mothers who
      had strong intentions to immunize their children in future and those with weaker
      intentions. RESULTS: Of the participants, 79.6% had a positive attitudes towards
      vaccination, 77.5% had a high perceived social support, 63.2% had a high
      perceived behaviour control and 87.3% strongly intended to have their child
      vaccinated. Strong intention to vaccination was significantly associated with the
      positive behavioral attitudes [adjusted odds ratios (AOR) = 3.2, 95% CI: 2.3
      5.7], the high perceived social support (AOR = 2.8, 95% CI: 1.8-3.6), the
      perceived ease of undergoing vaccination (AOR = 2.1, 95% CI: 1.6-3.3),
      respectively. CONCLUSIONS: It was recommended that interventions focused on trust
      building, promoting social norms, changing the negative attitude would be
      effective to enhance the maternal acceptance on vaccination.

PMID- 30235058
TI  - Intradermal immunization with botulinum neurotoxin serotype E DNA vaccine induces
      humoral and cellular immunity and protects against lethal toxin challenge.
AB  - Botulinum neurotoxins (BoNTs) produced by the spore-forming, gram-positive,
      anaerobic bacterium Clostridium botulinum are the most toxic substances known and
      cause botulism, flaccid paralysis, or death. Owing to their high lethality, BoNTs
      are classified as category A agents by the Centers for Disease Control (CDC).
      Currently, there are no vaccines available to protect against BoNTs, so the rapid
      development of a safe and effective vaccine is important. DNA-based vaccines have
      recently drawn great attention because they can be developed quickly and can be
      applied in mass vaccination strategies to prevent disease outbreaks. Here, we
      report on the immunogenic and protective efficacy of a DNA vaccine, encoding a 50
      kDa carboxy-terminal fragment of the BoNT serotype E heavy chain, which is
      delivered via an intradermal route. This plasmid DNA vaccine induced robust
      humoral and cellular BoNT/E-specific immune responses and completely protected
      animals against lethal challenge with BoNT/E. These results not only indicate
      that DNA vaccines could be further developed as safe and effective candidates for
      vaccines against BoNTs but also suggest a possible approach for developing
      vaccines that protect against bio-threat toxins.

PMID- 30235059
TI  - Hair hormones in male youth with internet gaming disorder.
AB  - OBJECTIVES: Internet gaming disorder (IGD) is associated with altered
      physiological reactivity to psychosocial stress. Findings from a previous study
      on alterations of basal hypothalamic-pituitary-adrenal (HPA) axis functioning,
      indexed by differences in hair hormone levels (i.e., cortisol) in IGD patients
      compared to matched controls, were limited by a small sample size. METHODS:
      Following the protocol of the previous study, male patients with IGD (n = 31) and
      controls (n = 31) matched for age, educational status and smoking were recruited.
      Sociodemographic and clinical characteristics were assessed using structured
      interviews and self-reports. Hair samples were taken for the analysis of
      cortisol, cortisone, testosterone, progesterone, dehydroepiandrosterone (DHEA),
      and corticosterone. RESULTS: Groups showed no significant differences on cortisol
      (d = -0.10, 95%CI (-0.60; 0.40)), cortisone (d = -0.10, 95%CI (-0.60; 0.40)),
      testosterone (d = -0.00, 95%CI (-0.51; 0.51)), progesterone (d = -0.46, 95%CI (
      0.96; 0.05)), DHEA (d = -0.04, 95%CI (-0.54; 0.47)) or corticosterone (d = -0.19,
      95%CI (-0.69; 0.32)). Associations between hair hormone concentrations, symptom
      severity and sociodemographic variables were weak and did not survive correction
      for multiple testing. CONCLUSIONS: Unlike other psychiatric disorders, effects of
      IGD and associated psychopathology on basal HPA axis functioning, indexed by hair
      hormone levels, are negligible. Future studies need to rule out potential effects
      of sex, age and long-term pathology on these findings.

PMID- 30235061
TI  - From barriers to channels.

PMID- 30235060
TI  - Viral etiological causes of febrile seizures for respiratory pathogens (EFES
      Study).
AB  - BACKGROUND: Febrile seizure is the most common childhood neurological disorder,
      is an important health problem with potential short- and long-term complications,
      also leading to economic burden and increased parental anxiety about fevers and
      seizures occurring in their children. There are no routine recommendation to
      detect etiological causes of FS for neurological perspective, further knowledge
      about the etiological causes of FS in children will support preventive measures
      and follow-up strategies. The aim of this study is to evaluate the percentage of
      respiratory viruses in children with FS. METHODS: This prospective multicenter
      study, entitled "Viral etiological causes of febrile seizures for respiratory
      pathogens (EFES Study)" examined representative populations in eight different
      cities in Turkey between March 1, 2016 and April 1, 2017. Nasopharyngeal swabs
      were taken from all children at presentation. A respiratory multiplex array was
      performed to detect for influenza A and B; respiratory syncytial virus A and B;
      human parainfluenza virus 1-2-3 and 4; human coronavirus 229E and OC43; human
      rhinovirus; human enterovirus; human adenovirus; human bocavirus; human
      metapneumovirus. RESULTS: During the study period, at least one virus was
      detected in 82.7% (144/174) of children with FS. The most frequently detected
      virus was adenovirus, followed by influenza A and influenza B. Detection of more
      than one virus was present in 58.3% of the children with FS, and the most common
      co-existence was the presence of adenovirus and influenza B. In children younger
      than 12 months, Coronavirus OC43 was the most common, while influenza A was most
      frequently observed in children older than 48 months (p < 0.05). Human bocavirus
      was common in children who experienced complex FS, while respiratory syncytial
      virus (RSV) A was more common in children who experienced simple FS. Influenza B
      virus was the most common virus identified in children who were experiencing
      their first incidence of FS (p < 0.05). CONCLUSIONS: This study indicates that
      respiratory viruses are important in the etiology of FS in children. The results
      show that antibiotics must be prescribed carefully in children with FS since the
      majority of cases are related to viral causes. Widespread use of the existing
      quadrivalent influenza vaccine might be useful for the prevention of FS related
      to the flu. Further vaccine candidates for potential respiratory pathogens,
      including RSV, might be helpful for the prevention of FS.

PMID- 30235062
TI  - Impact of parallax and interpupillary distance on size judgment performances of
      virtual objects in stereoscopic displays.
AB  - Effective interactions in both real and stereoscopic environments require
      accurate perceptions of size and position. This study investigated the effects of
      parallax and interpupillary distance (IPD) on size perception of virtual objects
      in widescreen stereoscopic environments. Twelve participants viewed virtual
      spherical targets displayed at seven different depth positions, based on seven
      parallax levels. A perceptual matching task using five circular plates of
      different sizes was used to report the size judgment. The results indicated that
      the virtual objects were perceived as larger and smaller than the corresponding
      theoretical sizes, respectively, in negative and positive parallaxes. Similarly,
      the estimates from participants with small IPDs were greater than the predicted
      estimates. The findings of this study are used to explain human factor issues
      such as the phenomenon of inaccurate depth judgments in virtual environments,
      where compression is widely reported, especially at farther egocentric distances.
      Furthermore, a multiple regression model was developed to describe how the size
      was affected by parallax and IPD. Practitioner Summary: The study investigates
      the effects of parallax and interpupillary distance on size perception of virtual
      targets in a stereoscopic environment. Virtual objects were perceived as larger
      in negative and smaller in positive parallax. Also, size estimates were greater
      than the theoretical sizes for participants with smaller IPD. A multiple
      regression model explains the impact of parallax and measured IPD. Abbreviations
      IPD interpupillary distance VR virtual eality HMD head mounted-displays 2AFC two
      alternative forced choice IOD interocular distance PD pupillary distance ANOVA
      analysis of variance.

PMID- 30235063
TI  - More important and surprising actions of a moral exemplar trigger stronger
      admiration and inspiration.
AB  - Admiring a moral role model has been found to inspire people to become better
      persons themselves. But what are the antecedents that trigger admiration and thus
      make inspiration more likely? In three studies, we tested the effect of perceived
      importance and perceived surprisingness of the moral action on resulting
      admiration and inspiration. Study 1 finds that perceived importance, and to a
      lesser extent, the perceived surprisingness of a moral action, are related to
      stronger admiration. Manipulating the perceived importance of the same moral
      action by only providing a little more detail about the moral action, could
      increase the admiration and inspiration the role models elicit (Studies 2 and 3).
      Our findings help the understanding of how moral exemplars trigger inspiration
      and provide valuable insights into further investigation toward the causes of
      admiration.

PMID- 30235064
TI  - Assessing the impact of converting roundabouts to traffic signals on vehicle
      emissions along an urban arterial corridor in Qatar.
AB  - The type of control at intersections has a major effect on the operation of any
      urban corridor. Different pre-defined procedures are available to calculate some
      of the main operational characteristics, such as capacity, delay, and level of
      service in order to select the best type of control. However, there are other
      important factors that affect major arterials operational characteristics, which
      are not fully addressed, such as the impact of emissions. In this study, a
      microscopic simulation approach using VISSIM and MOVES was developed to assess
      the environmental effect of converting four three-lane roundabouts to signalized
      intersections along a heavily congested urban corridor in Qatar. A decision was
      made to switch all roundabouts to traffic signals for better operations.
      Preliminary results indicated that the signal control outperformed the roundabout
      in the range of 37% to 43% reduction in emissions. A more detailed analysis
      revealed that roundabout corridor operations effect on emission rates are
      divergent from signalized corridors, particularly upstream and downstream of the
      intersections. Immediate roundabout upstream approaches are driver behavior
      dependent; characterized by substantial coasting at lower speeds and subsequent
      re-accelerating with less idling, described as acceleration events, which
      resulted in high emission rates while signalized corridors' s are signal timing
      dependent; characterized by ample idling with less coasting and re-acceleration,
      resulting in reduced emission rates. The results also revealed that there was no
      significant difference between emission rates in the vicinity of the two types of
      control. Both recorded nearly the same emission rate.

PMID- 30235065
TI  - We Do Not Know What Queers Can Do: LGBT Community Between (In)visibility and
      Culture Industry in Serbia at the Beginning of the 21st Century.
AB  - This article analyzes the ways in which LGBT community in Serbia is produced as
      both visible and invisible in activism and culture industry through affective
      labor performed as identification with the project of Europeanization of Serbian
      society (social subjection), and immaterial labor performed within culture
      industry by participating in the clubbing scene (machinic enslavement). LGBT
      community in Serbia has a potential for becoming other than a homonormativized
      group of consumers, especially when those who are produced as invisible are taken
      into account, and spatially and socially marginalized spaces where alternative
      forms of culture and politics are made and lived.

PMID- 30235066
TI  - Persistent complex bereavement symptoms explain impairments above depression,
      posttraumatic stress, and separation anxiety: an incremental validity study.
AB  - The present study examined the incremental validity of persistent complex
      bereavement disorder (PCBD) symptoms using an on-line survey of 255 bereaved
      college students. A series of hierarchical multiple regression analyses examined
      the extent to which PCBD symptoms explained unique variance in different domains
      of life impairment, beyond symptoms of depression, posttraumatic stress, and
      separation anxiety. The results supported the incremental validity of PCBD
      symptoms for fear of future losses, sleep impairment, and work/social impairment.
      However, PCBD symptoms did not account for loneliness scores. These findings
      collectively support the validity and clinical utility of the DSM-5's PCBD
      construct.

PMID- 30235067
TI  - Exploring the impact of out-of-pocket costs on the quality of life of Canadian
      cancer patients.
AB  - OBJECTIVE: To explore cancer patients' perspective about the impact of financial
      burden on quality of life. METHODS: A qualitative descriptive approach was
      utilized. In-depth interview transcripts from 14 survivors were subjected to a
      thematic analysis. RESULTS: All participants experienced reduced income and
      increased out-of-pocket costs following their diagnosis. None worked during their
      treatment interval. They described profound impacts on the social, psychological,
      and spiritual domains of quality of life from the financial challenges. Many were
      worried about having sufficient funds to support themselves in the long term and
      felt this added to the burden they were carrying. Most found the financial
      challenges surprising and unexpected. Additionally, the impact was also
      experienced by their family members. IMPLICATIONS: Healthcare providers ought to
      be aware of the potential impact financial challenges can have and the distress
      they bring about. A discussion about financial concerns needs to occur at the
      beginning of the cancer journey, with appropriate resources made available, and
      monitored regularly.

PMID- 30235068
TI  - The role of theory in understanding grief.
AB  - As the tandem fields of bereavement care and research have evolved, so too has a
      keener appreciation of the role of theory in advancing both. This article
      succinctly summarizes the function of theory in directing investigation and
      intervention in grief and grief therapy and describes Meaning Reconstruction as
      one exemplar of this bootstrapping process, leading to evidence-based conceptual
      refinements and creative contributions to clinical practice.

PMID- 30235069
TI  - Rapid determination of Alternaria mycotoxins in tomato samples by pressurised
      liquid extraction coupled to liquid chromatography with fluorescence detection.
AB  - A sensitive and reliable method using pressurised liquid extraction (PLE)
      followed by molecularly imprinted solid phase extraction (MISPE) and high
      performance liquid chromatography with fluorescence detection (HPLC-FLD) has been
      developed for the analysis of alternariol (AOH) and alternariol monomethyl ether
      (AME) in tomato samples. Influence of several extraction parameters that affect
      PLE efficiency were evaluated for the simultaneous extraction of both mycotoxins
      in the selected samples. AOH and AME were optimally extracted using MeOH/water
      (25:75, v/v) at 70 degrees C as solvent, a pressure of 1000 psi and a single
      extraction cycle. The resulting PLE extracts were pre-concentrated by molecularly
      imprinted solid phase extraction (MISPE) cartridges followed of analysis by HPLC
      with fluorescence detection (lambdaexc = 258, lambdaem = 440 nm). The proposed
      method was applied to the analysis of AOH and AME in fortified tomato samples (20
      72 ug. kg-1) with recoveries of 84-97% (RSD < 8%, n = 6) for AOH and 67-91% (RSD
      < 13%, n = 6) for AME. The detection limit for AOH and AME were 7 and 15 ug. kg
      1, respectively. The ensuing PLE-MISPE-HPLC-FLD method was validated for the
      analysis of both mycotoxins in tomato samples in accordance with European
      Commission Decision 2002/657/EC.

PMID- 30235070
TI  - The Politics of Sexual Citizenship: Negotiating Acts of Citizenship Among Non
      Heterosexuals in Hong Kong.
AB  - The notion of sexual citizenship has been developed over the past two decades,
      and its discussion has been expanded to other regions. This article investigates
      the claiming of rights by non-heterosexuals in Hong Kong to achieve two
      objectives: to articulate the importance of the rights claiming process,
      particularly regarding how non-heterosexuals are being transformed to become
      claimants through rights claims, and to extend the notion of sexual citizenship
      in East Asia, particularly in the Hong Kong context. The findings show four
      distinctive characteristics of sexual citizenship in Hong Kong. Non-heterosexuals
      are found to have faced different struggles and barriers before or during the
      process of claiming rights, including restricted welfare rights access in various
      social institutions. Furthermore, the development of sexual citizenship in the
      Hong Kong local context is found to be limited.

PMID- 30235071
TI  - What Belongs to You.

PMID- 30235072
TI  - Moderating Effects of Community Social Capital on Depression in Later Years of
      Life: A Latent Interaction Model.
AB  - OBJECTIVE: This study tested the stress-buffering model and examined the
      buffering role of community social capital on late-life depression. METHODS: This
      study used the data from the second wave of National Social Life, Health, and
      Aging Project (NSHAP, 2010-2012). In the present study, a total of 2,362 older
      adults aged 65 and older (Mage = 74.5, SD = 6.69) were included. Latent moderated
      structural equations model was tested by comparing the main effect model and
      interaction model. Depression, stress, and community social capital were
      constructed as latent variables for the analyses. RESULTS: The main effect model
      was acceptable: chi2 (df = 334) = 1596.4, p = .000; RMSEA = .04 (.038 - .042);
      CFI = .91; and SRMR = .05. And interaction model was significant (D = 35.0, p <
      .001). The latent constructs of stress (beta = . 50, p < .001) and community
      social capital (beta = -.14, p < .001) not only had a direct effect on
      depression, but their interaction was also significant (beta = -.21, p < .01).).
      The group with a high level of social capital presented a relatively stable slope
      in the prediction of stress on depression, suggesting their resilience, while the
      group with a low level of community social capital demonstrated a steep slope,
      indicating heighten vulnerability to depression when faced with stress.
      CONCLUSIONS: The findings support the hypothesis of stress buffering model and
      identify the protective effects of community social capital on depression of
      older adults. CLINICAL IMPLICATIONS: Older adults with lower community social
      capital are particularly vulnerable to depression. The results highlight that
      practitioners and policymakers should pay more attention to finding ways to
      enhance community resources to improve older adults' mental health.

PMID- 30235073
TI  - Striving for Prestige in Samoa: A Comparison of Men, Women, and Fa'afafine.
AB  - In numerous non-Western cultures around the world, a small but meaningful
      proportion of individuals occupy alternative gender categories beyond the
      man/woman binary. A substantial body of past research has shown that feminine,
      same-sex attracted males in Samoa--a nonbinary gender known as fa'afafine--are
      more altruistic toward their nieces and nephews than are Samoan men and women.
      The present study examined the degree to which these kin-directed altruistic
      tendencies of fa'afafine are motivated by striving for prestige, and hence
      demonstrating value, within their family. Results showed that cisgender men and
      women do not differ in the degree to which they seek familial recognition of
      their altruistic behavior toward nieces and nephews. However, compared to men,
      fa'afafine sought significantly more acknowledgment of this altruism. These
      results illustrate one proximate cognitive mechanism for the elevated kin
      directed altruism of fa'afafine and highlight the importance of the sociocultural
      context in which these motivations develop.

PMID- 30235074
TI  - 'The body is a battleground for unwanted and unexpressed emotions': exploring
      eating disorders and the role of emotional intelligence.
AB  - Emotional difficulties have been observed in individuals with eating disorders
      across awide range of studies, including poor interoceptive awareness, confusion
      of emotionalstates and difficulties with emotional language. Literature has
      linked these difficultieswith emotional functioning as being an important factor
      related to the core aetiology ofeating disorders, however limited knowledge
      exists to how this impacts on professionalability to engage patients within
      treatment as a result of such dysfunction. Using aqualitative design this paper
      explores how facets of Emotional intelligence (EI) arerelated to the experience
      of an eating disorder. The study sampled a total of 32participants with either a
      professional background working with eating disorders (n=25)or participants with
      personal lived experience (n=5), with a number of the participants(n=13)
      identified as having dual roles. The findings of the study show that aspects of
      EIsuch as emotional regulation and lack of an emotional language are considered
      to beat the core of the onset and maintenance of these disorders. Additional
      aspects ofemotional awareness and expression were found to be related to
      treatmentdisengagement and difficulties. Building on previous literature, this
      paper found suchemotional deficits as a transdiagnostic issue rather than
      specifically anorexia nervosa.Furthermore, such dysfunction was seen by
      professionals to have a considerableimpact on therapeutic relationships and
      successful treatment. These findings provideinsight into the potential
      applications that EI may have in addressing aspects of theeating disorder to
      create better outcomes for treatment and intervention models.

PMID- 30235075
TI  - The Evolution Will Not Be Broadcast (or Published): Social Capital, Assimilation,
      and the Changing Queer Community.
AB  - Widespread technological advances, coupled with social and political success by
      the LGBTQ rights movement in the decades following the Stonewall uprising in
      1969, have resulted in a dramatic evolution in the queer community. But increases
      in visibility, acceptance, and assimilation of queers into mainstream culture and
      cultural institutions have been accompanied by mainstream gentrification of
      formerly queer neighborhoods, more specialized social alternatives to bars and
      bookstores, and diminished interest in and audiences for niche-appeal media. At
      the same time, other institutions in the LGBTQ community, including the queer
      civic and fraternal organization The Court, the Gay Lesbian Straight Education
      Network (GLSEN), social media platforms such as Grindr, and online journalism
      cites such as Towleroad have become destination sites for many in cyberspace. In
      this article, I argue that social network theory (SNT) offers efficacy in both
      explaining and predicting institutional success in the evolving queer community
      and that queers, regardless of age, location, and relationship status, will
      affiliate with institutions that offer them to potential for the accumulation of
      social capital.

PMID- 30235076
TI  - Freezing fertility or freezing false hope? A content analysis of social egg
      freezing in U.S. print media.
AB  - In 2012, the American Society for Reproductive Medicine (ASRM) lifted the
      experimental label on oocyte preservation, but cautioned against women using it
      to avoid age-related infertility, known as social egg freezing (SEF). In 2014,
      Facebook and Apple announced that they would offer SEF as a workplace benefit.
      Within the context of a rapidly growing market for SEF, we were interested in how
      these two decisions affected media discussions, given that such discourse can
      strongly influence public perceptions and behaviors. We used a content analysis
      methodology to code 138 articles published in U.S. newspapers and magazines
      between 2012 and 2015. Focusing on a financial concern over the cost of SEF and
      the lack of insurance for SEF, we found that media portrayals of SEF pivot away
      from the ethical principle of nonmaleficence centered in the ASRM decision to
      discourage SEF. Instead, they highlight an issue of justice that can be remedied
      through the offer of SEF as a workplace benefit. Overall, media portrayals of SEF
      paint a simplistic and rosy picture that more options, especially more
      reproductive and economic options, automatically enhance women's autonomy.

PMID- 30235077
TI  - Tumbling Into Queer Utopias and Vortexes: Experiences of LGBTQ Social Media Users
      on Tumblr.
AB  - Drawing on one year of fieldwork with LGBTQ youth, I explore the ways Tumblr, a
      microblogging and social networking site, has become a vibrant center of queer
      discourse and collectivity. I argue that for LGBTQ users, Tumblr simultaneously
      generates the specter of a "queer utopia"-a space where queer potential
      flourishes and more expansive ways to think about the future materialize-and
      queer "vortextuality"-an experience of being sucked into an online black hole
      with severe limitations. Furthermore, the user experience on the site underscores
      the profound vulnerability of queer individuals and communities in digital,
      corporatized space.

PMID- 30235078
TI  - Disclosing Lesbian and Gay Male Sexual Orientation in Later Life: Attitudes of
      Younger and Older Generations in Eight Latin American Countries.
AB  - The purpose of this research was to explore attitudes toward older lesbians and
      gay men disclosing their sexual preferences in eight Latin American countries.
      The sample consisted of 1,539 participants belonging to three age groups (18-29
      years, 60-69 years, and 70 years and over). Their answers to two open-ended
      questions were content-analyzed, and binary logistic regressions were run on the
      extreme attitudinal categories. Results showed that although most attitudes were
      positive, a solid percentage of participants still expressed different kinds of
      derogatory attitudes. Men (as compared to women) and participants who were more
      religious and less educated tended to hold more negative attitudes toward
      lesbians and gay men. Both older samples were more prejudiced than the younger
      one, and attitudes also varied according to country. There was a general trend
      showing more positive attitudes toward older lesbians and gay men in those
      countries where sexual minorities' rights are better assured, which suggests that
      measures to protect sexual minorities and to make sexual diversity in older age
      visible could be advisable.

PMID- 30235079
TI  - Queer Relationality as Family: Yas Fats! Yas Femmes! Yas Asians!
AB  - In this essay, we, as queer subjects, share our embodied experiences to
      rearticulate and reimagine possible and impossible performances of queer
      relationality as family. We collaboratively pay careful and nuanced attention to
      our queer performative roles of becoming and being femmes as referring points of
      this critical queer engagement. To do so, we adapt methodological implications of
      autoethnography and intersectional reflexivity. Thereby, we take further steps to
      explore an anti-anti-relational landscape of queerness that works on and against
      hegemonic, heteronormative, and homonormative paradigms of relating.

PMID- 30235080
TI  - Failed Fatherhood and the "Trap of Ambivalence": Assimilation, Homonormativity,
      and Effeminophobia in The New Normal.
AB  - The New Normal, NBC's 2012 sitcom about gay fathers, contradicts itself: While
      striving to normalize gay men as respectable parents, the show often mocks
      feminine gay men as unsuitable parents. I take this "effeminophobic"
      contradiction as a case study to extend queer theory's critique of LGBTQ
      assimilation. I read The New Normal through a joint framework linking Lisa
      Duggan's well-known critique of homonormativity with Zygmunt Bauman's critique of
      Jewish cultural assimilation. This connection clarifies how the pitfalls of
      homonormative assimilation, like The New Normal's self-stigmatizing humor,
      reflect a broader "trap of ambivalence" inherent to assimilation itself. In turn,
      this insight illustrates how queer theory can benefit from seeking explicitly
      Jewish perspectives on sexuality. This study also invites queer theory to analyze
      how sexual difference is co-structured with Jewish difference.

PMID- 30235081
TI  - A shared medication scheme for community dwelling older patients with
      polypharmacy receiving home health care: role of the community pharmacist.
AB  - BACKGROUND AND OBJECTIVE: An accurate medication scheme may be a useful tool to
      improve medication safety in primary care. This study aimed to identify (1)
      pharmacists' alterations to nurse medication schemes and (2) potential
      improvements to the contribution of the community pharmacist to a shared
      medication scheme within a multidisciplinary collaboration. Dosing frequency,
      potentially incorrect moments of intake, drug-drug interactions and medication
      complexity (quantified by the Medication Regimen Complexity Index, MRCI) were
      investigated. Setting and method: Observational study in community dwelling older
      patients (>=70 years) with polypharmacy receiving home health care (i.e.
      medications being prepared and/or administered by home care nurses). Home care
      nurses provided the community pharmacist with the original medication scheme
      ('nurse medication scheme'), subsequently the community pharmacist generated a
      standardized 'pharmacist medication scheme' which was uploaded on an electronic
      health platform (Vitalink). The researcher recorded all pharmacists' alterations
      and looked for possible additional improvements ('researcher medication scheme').
      RESULTS: Pharmacists made 482 alterations to the nurse medication schemes of 31
      patients. Most important alterations included adding indication (61%), generic or
      brand name (18%) and moment of intake (9%). Pharmacists did not reduce dosing
      frequency. MRCI scores (median [IQR]) significantly differed between pharmacist
      (38 [15]) and nurse medication schemes (32 [11]) (p < 0.001) and between nurse
      (32 [11]) and researcher medication schemes (40 [15]) (p < 0.001). CONCLUSION:
      Alterations made by the community pharmacists enable more complete and accurate
      medication schemes; however, there is room for improvement in optimizing the
      patient's medication scheme in a multidisciplinary collaboration.

PMID- 30235082
TI  - Ethical Issues in Intrauterine Myelomeningocele Surgery.
AB  - Intrauterine surgery shows that the prognosis of neonates with myelomeningocele
      (MMC) has improved, both in survival and in quality of life. In order to study
      the current efficacy of intrauterine surgery for MMC and to make an ethical
      analysis of its proportionality, we conducted a PubMed search using the keywords
      "myelomeningocele", "intrauterine surgery", "MOMS", and "trial". Thirty-eight
      articles were found. The literature investigated the risks and benefits of
      intrauterine surgery based on the physiological parameters of MMC. Intrauterine
      surgery produces clear benefits. However, it also has disadvantages, such as
      premature birth, fetal or neonatal death, and uterine complications. The option
      of surgery is positive. However, since the intervention is risky, the final
      decision must be prudential, and thus should involve an ethical analysis of
      therapeutic proportionality. This requires a specific clinical evaluation of the
      fetus ensuring fetal survival in all cases and minimizing the risks arising from
      extremely premature birth.

PMID- 30235083
TI  - Bilateral Polycystic Kidneys and Focal Renal Cystadenoma in a Pygmy Sperm Whale (
      Kogia breviceps).
AB  - An adult male pygmy sperm whale ( Kogia breviceps) stranded alive at a beach in
      Florida, USA, in 2016. Main postmortem examination findings included bilateral
      multifocal variably sized renal cysts, focal renal cystadenoma, and mild dilation
      of the renal pelvises. The role of these renal lesions in the stranding of this
      whale is unknown.

PMID- 30235084
TI  - Hematologic Values of Healthy and Sick Free-ranging Lesser Flamingos (
      Phoeniconaias minor) in Kenya.
AB  - We determined hematologic parameters of five healthy and nine sick free-ranging
      Lesser Flamingos ( Phoeniconaias minor) from Lake Nakuru, Kenya. Heterophilia and
      lymphopenia were evident in sick birds, with up to 7.5-fold higher heterophil-to
      lymphocyte ratio in sick birds compared to healthy birds. Leucopenia was present
      in a few sick birds. A higher than normal packed cell volume was observed in
      birds that had evidence of acute disease, whereas a lower than normal packed cell
      volume was seen in birds with evidence of prolonged sickness. Healthy birds had
      higher total white blood cell counts and lymphocyte counts and lower heterophil
      counts than zoo flamingos. Most sick birds were diagnosed with septicemia,
      occasionally with fibrinous exudation into the coelomic cavities. One bird had
      mycobacterial granulomas, one had a corynebacterium-associated wing abscess, and
      one had a wing fracture. We provide hematologic data for free-ranging Lesser
      Flamingos and compare the parameters of sick and healthy birds.

PMID- 30235085
TI  - Serologic and Virologic Evidence of Influenza A Viruses in Wild Boars ( Sus
      scrofa) from Two Different Locations in Italy.
AB  - Swine influenza viruses (SIVs) have been repeatedly demonstrated to circulate in
      wild boar ( Sus scrofa) populations, whereas no evidence of exposure to avian
      influenza viruses (AIVs) has been described in wild boar. To better understand
      how different environments may influence the ecology of influenza A viruses
      (IAVs) in wild suid populations, we examined biologic samples of wild boars from
      two study areas represented by an upland (UL) and a wetland (WL) in northern and
      central Italy, respectively. Serum samples were collected from 388 wild boars
      sampled in the UL, whereas both a serum sample and a nasal swab were obtained
      from each of 35 wild boars sampled in the WL. Twenty of 388 (5.2%) sera from the
      UL were positive by enzyme-linked immunosorbent assay for the presence of
      antibodies against influenza A nucleoprotein and some of these samples showed
      antibodies by hemagglutination inhibition to SIVs of H1N1 (1/20), H1N2 (10/20),
      and H3N2 (1/20) antigenic subtypes. No IAV-seropositive wild boar was detected in
      the WL, although one of 35 animals was found to be IAV-positive by both a reverse
      transcriptase PCR and a real-time reverse transcriptase PCR. We hypothesize an
      SIV exposure for IAV-seropositive wild boars occupying the UL, whereas a possible
      AIV spillover from aquatic bird species-natural reservoirs of IAVs-to wild boars
      in the WL cannot be ruled out. Further research is needed to better understand
      the role played by wild boars in IAV ecology in Mediterranean habitats.

PMID- 30235086
TI  - Oropharyngeal Trichomonosis Due to Trichomonas Gypaetinii in a Cinereous Vulture
      ( Aegypius Monachus) Fledgling in Spain.
AB  - A juvenile Cinereous Vulture ( Aegypius monachus) fledgling was found
      disorientated on the roof of a building in Madrid City, Spain, in October 2016. A
      veterinary examination revealed multiple plaques distributed throughout the
      oropharyngeal cavity. Lesions were located under the tongue and at the choanal
      slit, hard palate, and esophagus opening and ranged from 2 to 7 mm, coalescing in
      areas up to 2 cm, with a yellowish color of the surface. Motile trichomonad
      trophozoites were detected in fresh wet mount smears from the lesions. Sequence
      analysis of the internal transcribed spacer (ITS)1/5.8S/ITS2 and small subunit
      ribosomal RNA confirmed that Trichomonas gypaetinii was the etiologic agent.
      Microbiologic cultures did not reveal any pathogenic bacteria or fungi. The
      animal recovered successfully after treatment with metronidazole and trimethoprim
      sulfamethoxazole and was later released in a suitable habitat. Avian
      trichomonosis lesions caused by T. gypaetinii have not been reported.

PMID- 30235088
TI  - Response to Open Peer Commentaries on ''Provider Conscientious Refusal of
      Abortion, Obstetrical Emergencies, and Criminal Homicide Law''.

PMID- 30235087
TI  - Paclitaxel With Inhibitor of Apoptosis Antagonist, LCL161, for Localized Triple
      Negative Breast Cancer, Prospectively Stratified by Gene Signature in a Biomarker
      Driven Neoadjuvant Trial.
AB  - PURPOSE: There are currently no targeted therapies approved for triple-negative
      breast cancer (TNBC). A tumor necrosis factor alpha ( TNFalpha)-based gene
      expression signature (GS) predictive of sensitivity to LCL161, inhibitor of
      apoptosis antagonist, was translated into a clinical assay and evaluated in a
      neoadjuvant trial. PATIENTS AND METHODS: Women with localized TNBC (T2/N0-2/M0)
      were prospectively stratified by GS status and randomly assigned (1:1) to receive
      oral LCL161 (1,800 mg once per week) and intravenous paclitaxel (80 mg/m2 once
      per week; combination arm) or paclitaxel alone (control arm) for 12 weeks,
      followed by surgery. The primary objective was to determine whether neoadjuvant
      LCL161 enhances efficacy of paclitaxel, defined by > 7.5% increase in the
      pathologic complete response (pCR, breast) rate, stratified by GS. RESULTS: Of
      209 patients enrolled (207 with valid GS scores), 30.4% had GS-positive TNBC. In
      the GS-positive group, pCR was higher in the combination versus the control arm
      (38.2% v 17.2%), with 88.8% posterior probability of > 7.5% increase in pCR.
      However, in the GS-negative group, the pCR was lower in the combination group
      (5.6% v 16.4%), with 0% posterior probability of > 7.5% increase in pCR. A higher
      incidence of grade 3 or 4 adverse events in the combination arm included
      neutropenia (24.5%) and diarrhea (5.7%). Overall, 19 patients (18.1%) in the
      combination arm discontinued treatment because of adverse events, including
      pyrexia (n = 5), pneumonia (n = 4), and pneumonitis (n = 4), versus five patients
      (4.9%) in the control arm. CONCLUSION: This neoadjuvant trial provides evidence
      supporting a biomarker-driven targeted therapy approach for selected patients
      with GS-positive TNBC and demonstrates the utility of a neoadjuvant trial for
      biomarker validation and drug development, but also highlights toxicity risk.
      Future neoadjuvant clinical trials should carefully weigh these considerations
      for targeted therapy development in biomarker-defined TNBC.

PMID- 30235089
TI  - Review of Lori A. Roscoe and David Schenck, Communication and Bioethics at the
      End of Life: Real Cases, Real Dilemmas.

PMID- 30235090
TI  - Uterus Transplantation: Response to Open Peer Commentaries on the Ethics of Using
      Deceased Versus Living Donors.

PMID- 30235091
TI  - The Ethics of Smart Pills and Self-Acting Devices: Autonomy, Truth-Telling, and
      Trust at the Dawn of Digital Medicine.
AB  - Digital medicine is a medical treatment that combines technology with drug
      delivery. The promises of this combination are continuous and remote monitoring,
      better disease management, self-tracking, self-management of diseases, and
      improved treatment adherence. These devices pose ethical challenges for patients,
      providers, and the social practice of medicine. For patients, having both
      informed consent and a user agreement raises questions of understanding for
      autonomy and informed consent, therapeutic misconception, external influences on
      decision making, confidentiality and privacy, and device dependability. For
      providers, digital medicine changes the relationship where trust can be verified,
      clinicians can be monitored, expectations must be managed, and new liability
      risks may be assumed. Other ethical questions include direct third-party
      monitoring of health treatment, affordability, and planning for adverse events in
      the case of device malfunction. This article seeks to lay out the ethical
      landscape for the implementation of such devices in patient care.

PMID- 30235092
TI  - Digital Medicine and Ethics: Rooting for Evidence.

PMID- 30235093
TI  - In Defense of "Denial": Difficulty Knowing When Beliefs Are Unrealistic and
      Whether Unrealistic Beliefs Are Bad.
AB  - Bioethicists often draw sharp distinctions between hope and states like denial,
      self-deception, and unrealistic optimism. But what, exactly, is the difference
      between hope and its more suspect cousins? One common way of drawing the
      distinction focuses on accuracy of belief about the desired outcome: Hope, though
      perhaps sometimes misplaced, does not involve inaccuracy in the way that these
      other states do. Because inaccurate beliefs are thought to compromise informed
      decision making, bioethicists have considered these states to be ones where
      intervention is needed either to correct the person's mental state or to persuade
      the person to behave differently, or even to deny the person certain options
      (e.g., another round of chemotherapy). In this article, we argue that it is
      difficult to determine whether a patient is really in denial, self-deceived, or
      unrealistically optimistic. Moreover, even when we are confident that beliefs are
      unrealistic, they are not always as harmful as critics contend. As a result, we
      need to be more permissive in our approach to patients who we believe are
      unrealistically optimistic, in denial, or self-deceived-that is, unless patients
      significantly misunderstand their situation and thus make decisions that are
      clearly bad for them (especially in light of their own values and goals), we
      should not intervene by trying to change their mental states or persuade them to
      behave differently, or by paternalistically denying them certain options (e.g., a
      risky procedure).

PMID- 30235094
TI  - Digital Medicine, Cybersecurity, and Ethics: An Uneasy Relationship.

PMID- 30235095
TI  - Resisting the Digital Medicine Panopticon: Toward a Bioethics of the Oppressed.

PMID- 30235096
TI  - "I Know I'm Going to Beat This": When Patients and Doctors Disagree About
      Prognosis.

PMID- 30235097
TI  - Digital Medicine: An Opportunity to Revisit the Role of Bioethicists.

PMID- 30235098
TI  - Adherence, Surveillance, and Technological Hubris.

PMID- 30235099
TI  - Surveillance and Digital Health.

PMID- 30235100
TI  - Response to Open Peer Commentaries on ''In Defense of 'Denial': Difficulty
      Knowing When Beliefs Are Unrealistic and Whether Unrealistic Beliefs Are Bad".

PMID- 30235101
TI  - Policing Compliance: Digital Medicine and Criminal Justice-Involved Persons.

PMID- 30235102
TI  - Getting Off the Leash.

PMID- 30235103
TI  - Denial and Dyads: Patients Whose Surrogates and Physicians Are Unrealistically
      Optimistic.

PMID- 30235104
TI  - When Denial Hurts the Children: An Argument for Accountability of Denial in
      Parental Decision Making.

PMID- 30235105
TI  - Tom of Finland.

PMID- 30235106
TI  - The effects of emotional content on source monitoring in fibromyalgia patients.
AB  - Source confusion refers to a person's failure to distinguish whether an event has
      been actually seen or simply imagined. Nevertheless, prior research has
      demonstrated a reduction of source confusion for negative arousing information.
      According to the emotional-congruence effect, this emotional benefit is likely
      observed in patients suffering from chronic pain. This hypothesis was tested on
      15 patients suffering of fibromyalgia syndrome (FMS) and 15 healthy women. In a
      source-monitoring task, participants had to decide whether positive, negative,
      and neutral words were imagined or seen with a picture. The results showed
      recognition deficits and more source confusion for FMS patients compared to
      controls. Contrary to the hypothesis of negativity bias in fibromyalgia, patients
      exhibited enhanced recognition for both positive and negative words. Moreover,
      they showed better source memory for the imagined items than for those seen with
      a picture. Overall, these results indicate that FMS affects episodic memory.

PMID- 30235107
TI  - AuNPs-PCL nanocomposite accelerated abdominal wound healing through photothermal
      effect and improving cell adhesion.
AB  - Accelerating wound healing with modified biomaterial has been an attracting field
      in both material science and medicine. Enhanced cell adhesion could be acquired
      by improving surface hydrophilicity, which contributes to accelerating wound
      healing. Chemical reaction has been used for surface modification, but this study
      used a simple and nontoxic method to improve the hydrophilicity. Polycaprolactone
      (PCL) scaffold has been regarded as promising material for wound healing while
      its surface is hydrophobic. Our study demonstrated enhanced hydrophilicity of PCL
      with AuNPs coating. AuNPs has good biocompatibility and excellent photothermal
      effect. The coating of AuNPs not only improved the cell adhesion, but also gave
      PCL the ability to inhibit the growth of bacteria. Animal study showed that the
      nanocomposites decreased lymphocytes and neutrophils, increased
      neovascularization and accelerated the abdominal wound healing, which was
      attributed to improved hydrophilicity and the antibacterial ability. In
      conclusion, we demonstrated that the nanocomposite could be used as a potential
      scaffold for cell adhesion and wound healing, and the role of AuNPs was
      highlighted as a kind of outstanding supplement.

PMID- 30235109
TI  - Pharmacogenetics of Antiretroviral Drug Response and Pharmacokinetic Variations
      in Indigenous South African Populations.
AB  - Interindividual and interethnic differences in response to antiretroviral drugs
      (ARVs) are influenced by genetic variation. The few genomic studies conducted
      among African-Americans and African ethnic groups do not reflect the extensive
      genetic diversity within African populations. ARVs are widely used in Africa.
      Therefore, genomic characterization of African populations is required before
      genotype-guided dosing becomes possible. The aim of this study was to determine
      and report on the frequency of genetic variants in genes implicated in metabolism
      and transport of ARVs in South African populations. The study comprised 48 self
      reported South African Colored (SAC) and 296 self-reported Black African (BA)
      individuals. Allele and genotype frequency distributions for 93 variants
      contributing to metabolism and transport of ARVs were compared between groups,
      and other global populations. Fifty-three variants had significant differences in
      allele and genotype frequencies when comparing SAC and BA groups. Thirteen of
      these have strong clinical annotations, affecting efavirenz and tenofovir
      pharmacokinetics. This study provides a summary of the genetic variation within
      genes implicated in metabolism and transport of ARVs in indigenous South African
      populations. The observed differences between indigenous population groups, and
      between these groups and global populations, demonstrate that data generated from
      specific African populations cannot be used to infer genetic diversity within
      other populations on the continent. These results highlight the need for
      comprehensive characterization of genetic variation within indigenous African
      populations, and the clinical utility of these variants in ARV dosing for global
      precision medicine. Population pharmacogenetics is a nascent field of global
      health and warrants further research and education.

PMID- 30235108
TI  - Is Procalcitonin Biomarker-Guided Antibiotic Therapy a Cost-Effective Approach to
      Reduce Antibiotic Resistant and Clostridium difficile Infections in Hospitalized
      Patients?
AB  - Antibiotics (AB) can reduce morbidity and mortality in the treatment of patients
      with sepsis and chronic obstructive pulmonary disease (COPD) exacerbations. Yet,
      AB overuse or misuse increases antibiotic resistance (ABR) and Clostridium
      difficile infections (CDI). This study projected the expected impact of a
      procalcitonin (PCT) biomarker testing strategy on incremental ABR cases and CDI,
      and costs of care in a population of patients hospitalized with suspected sepsis
      or a COPD exacerbation, in three European countries: the United Kingdom, Germany,
      and the Netherlands. Based on a systematic literature search and a decision
      model, we analyzed the number of ABR and CDI cases avoided and the incremental
      healthcare costs per patient from a societal perspective over the time horizon of
      a hospital stay. In the sepsis population, the PCT-guided antibiotic prescription
      strategy was projected to reduce the number of ABR cases with circa 6%, the
      number of CDI cases with 21%, and societal costs with circa ?1300 per patient. In
      the COPD population, the number of ABR and CDI cases is reduced with circa 50%,
      and societal cost savings ranged ?1701, ?2473, and ?2435 per patient in Germany,
      the Netherlands, and the United Kingdom, respectively. Model outcomes were most
      sensitive to the impact of the PCT-guided strategy on the number of intensive
      care unit days and general hospital ward days. Taken together, a PCT biomarker
      guided antibiotic management strategy is likely to reduce the number of ABR and
      CDI cases and generate cost savings in a population of patients hospitalized with
      suspected sepsis or with a COPD exacerbation.

PMID- 30235110
TI  - Abortion Rights: For and Against.

PMID- 30235111
TI  - MinION nanopore sequencing identifies the position and structure of bacterial
      antibiotic resistance determinants in a multidrug-resistant strain of
      enteroaggregative Escherichia coli.
AB  - The aim of this study was to use single-molecule, nanopore sequencing to explore
      the genomic environment of the resistance determinants in a multidrug-resistant
      (MDR) strain of enteroaggregative Escherichia coli serotype O51 : H30, sequence
      type (ST) 38. Sequencing was performed on the MinION Flow cell MIN-106 R9.4.
      Nanopore raw FAST5 reads were base-called using Albacore v1.2.1, converted to
      FASTA and FASTQ formats using Poretools v0.6.0, and assembled using Unicycler
      v0.4.2, combining the long-read sequencing data with short-read data produced by
      Illumina sequencing. The genome was interrogated against an antimicrobial
      resistance (AMR) gene reference database using blast. The majority of the 12 AMR
      determinants identified were clustered together on the chromosome at three
      separate locations flanked by integrases and/or insertion elements [region 1 
      catA, blaOXA-1, aac(6')-Ib-cr, tetA and blaCTX-M-15; region 2 - dfrA1 and aadA1;
      region 3 - catA, blaTEM-1, tetA and sul2]. AMR determinants located outside these
      three regions were a chromosomally encoded blaCMY-16, mutations in gyrA and parC,
      and two plasmid-encoded AMR determinants, blaOXA-181 and qnrS1 located on the
      same IncX3 plasmid. Long-read analysis of whole genome sequencing data identified
      mobile genetic elements on which AMR determinants were located and revealed the
      combination of different AMR determinants co-located on the same mobile element.
      These data contribute to a better understanding of the transmission of co-located
      AMR determinants in MDR E. coli causing gastrointestinal and extra-intestinal
      infections.

PMID- 30235112
TI  - Learning Rotation-Invariant and Fisher Discriminative Convolutional Neural
      Networks for Object Detection.
AB  - The performance of object detection has recently been significantly improved due
      to the powerful features learnt through convolutional neural networks (CNNs).
      Despite the remarkable success, there are still several major challenges in
      object detection, including object rotation, within-class diversity, and between
      class similarity, which generally degenerate object detection performance. To
      address these issues, we build up the existing state-of-the-art object detection
      systems and propose a simple but effective method to train rotation-invariant and
      Fisher discriminative CNN models to further boost object detection performance.
      This is achieved by optimizing a new objective function that explicitly imposes a
      rotation-invariant regularizer and a Fisher discrimination regularizer on the CNN
      features. Specifically, the first regularizer enforces the CNN feature
      representations of the training samples before and after rotation to be mapped
      closely to each other in order to achieve rotation-invariance. The second
      regularizer constrains the CNN features to have small within-class scatter but
      large between-class separation. We implement our proposed method under four
      popular object detection frameworks, including region-CNN (R-CNN), Fast R- CNN,
      Faster R- CNN, and R- FCN. In the experiments, we comprehensively evaluate the
      proposed method on the PASCAL VOC 2007 and 2012 data sets and a publicly
      available aerial image data set. Our proposed methods outperform the existing
      baseline methods and achieve the state-of-the-art results.

PMID- 30235113
TI  - Learning Local Descriptors by Optimizing the Keypoint-Correspondence Criterion:
      Applications to Face Matching, Learning From Unlabeled Videos and 3D-Shape
      Retrieval.
AB  - Current best local descriptors are learned on a large data set of matching and
      non-matching keypoint pairs. However, data of this kind are not always available,
      since the detailed keypoint correspondences can be hard to establish. On the
      other hand, we can often obtain labels for pairs of keypoint bags. For example,
      keypoint bags extracted from two images of the same object under different views
      form a matching pair, and keypoint bags extracted from images of different
      objects form a non-matching pair. On average, matching pairs should contain more
      corresponding keypoints than non-matching pairs. We describe an end-to-end
      differentiable architecture that enables the learning of local keypoint
      descriptors from such weakly labeled data. In addition, we discuss how to improve
      the method by incorporating the procedure of mining hard negatives. We also show
      how our approach can be used to learn convolutional features from unlabeled video
      signals and 3D models.

PMID- 30235114
TI  - Evaluation of Haptic Feedback on Bimanually Teleoperated Laparoscopy for
      Endometriosis Surgery.
AB  - : Robotic minimal invasive surgery is gaining acceptance in surgical care. In
      contrast with the appreciated 3D vision and enhanced dexterity, haptic feedback
      is not offered. For this reason robotics is not considered beneficial for
      delicate interventions such the endometriosis. Overall, haptic feedback remains
      debatable and yet unproven except for some simple scenarios such as Fundamentals
      of Laparoscopic Surgery exercises. OBJECTIVE: The present work investigates the
      benefits of haptic feedback on more complex surgical gestures, manipulating
      delicate tissue through coordination between multiple instruments. METHODS: A new
      training exercise, "Endometriosis Surgery Exercise" (ESE) has been devised
      approximating the setting for monocular robotic endometriosis treatment. A
      bimanual bilateral teleoperation setup was designed for laparoscopic laser
      surgery. Haptic guidance and haptic feedback are respectively offered to the
      operator. User experiments have been conducted to i) assess the validity of ESE
      and to ii) examine possible advantages of haptic technology during execution of
      bimanual surgery. RESULTS: i) Content and face validity of ESE was established by
      participating surgeons. Surgeons suggested ESE also as a means to train lasering
      skills, ii) interaction forces on endometriotic tissue were found to be
      significantly lower when a bilateral controller is used. Collisions between
      instruments and the environment were less frequent and so were situations marked
      as potentially dangerous. CONCLUSION: This study provides some promising results
      suggesting that haptics may offer a distinct advantage in complex robotic
      interventions were fragile tissue is manipulated. SIGNIFICANCE: Patients need to
      know whether it should be incorporated. Improved understanding of the value of
      haptics is important as current commercial surgical robots are widely used but do
      not offer haptics.

PMID- 30235115
TI  - New Similarity Metric for Registration of MRI to Histology: Golden Retriever
      Muscular Dystrophy Imaging.
AB  - OBJECTIVE: Histology is often used as a gold standard to evaluate non-invasive
      imaging modalities such as MRI. Spatial correspondence between histology and MRI
      is a critical step in quantitative evaluation of skeletal muscle in golden
      retriever muscular dystrophy (GRMD). Registration becomes technically challenging
      due to non-orthogonal histology section orientation, section distortion, and the
      different image contrast and resolution. METHODS: This study describes a 3-step
      procedure to register histology images with multi-parametric MRI: i.e.,
      interactive slice localization controlled by a 3D mouse, followed by an affine
      transformation refinement, and a B-spline deformable registration using a new
      similarity metric. This metric combines mutual information and gradient
      information. RESULTS: The methodology was verified using ex vivo high-resolution
      multi-parametric MRI with a resolution of 117.19 MUm (i.e., T1-weighted and T2
      weighted MRI images) and trichrome stained histology images acquired from the
      pectineus muscles of ten dogs (nine GRMD and one healthy control). The proposed
      registration method yielded an RMS error of 148.83 +/- 34.96 MUm averaged for 10
      muscle samples based on landmark points validated by 5 observers. The best RMS
      error averaged for 10 muscles, was 128.48 +/- 25.39 MUm. CONCLUSION: The
      established correspondence between histology and in vivo MRI enables accurate
      extraction of MRI characteristics for histologically confirmed regions (e.g.,
      muscle, fibrosis, fat). SIGNIFICANCE: The proposed methodology allows creation of
      a database of spatially registered multi-parametric MRI and histology. This
      database will felicitate accurate monitoring of disease progression and assess
      treatment effects non-invasively.

PMID- 30235116
TI  - Epilepsy-on-a-chip System for Antiepileptic Drug Discovery.
AB  - OBJECTIVE: Hippocampal slice cultures spontaneously develop chronic epilepsy
      several days after slicing and are used as an in vitro model of post-traumatic
      epilepsy. Here, we describe a hybrid microfluidic-microelectrode array (MUflow
      MEA) technology that incorporates microfluidic perfusion network and electrodes
      into a miniaturized device for hippocampal slice culture based antiepileptic drug
      discovery. METHODS: Field potential simulation was conducted to help optimize the
      electrode design to detect seizure-like population activity. Epilepsy-on-a-chip
      model was validated by chronic electrical recording, neuronal survival
      quantification, and anticonvulsant test. To demonstrate the application of MUflow
      MEA in drug discovery, we utilized a two-stage screening platform to identify
      potential targets for antiepileptic drugs. In Stage I, lactate and lactate
      dehydrogenase biomarker assays were performed to identify potential drug
      candidates. In Stage II, candidate compounds were retested with MUflow-MEA based
      chronic electrical assay to provide electrophysiological confirmation of
      biomarker results. RESULTS AND CONCLUSION: We screened 12 receptor tyrosine
      kinases inhibitors, and EGFR/ErbB-2 inhibitor and cFMS inhibitor were identified
      as novel antiepileptic compounds. SIGNIFICANCE: This epilepsy-on-a-chip system
      provides the means for rapid dissection of complex signaling pathways in
      epileptogenesis, paving the way for high-throughput antiepileptic drug discovery.

PMID- 30235117
TI  - Order-preserving Optimal Transport for Distances between Sequences.
AB  - We present new distance measures between sequences that can tackle local temporal
      distortion and periodic sequences with arbitrary starting points. Through viewing
      the instances of each sequence as empirical samples of an unknown distribution,
      we cast the calculations of distances between sequences as optimal transport
      problems. To preserve the inherent temporal relationships of the instances in
      sequences, we propose two methods through incorporating the temporal information
      into the spatial ground metric and concentrating the transport with two novel
      temporal regularization terms, respectively. The inverse difference moment
      regularization enforces local homogeneous structures in the transport, and the KL
      divergence with a prior distribution regularization prevents transport between
      instances with far temporal positions. We show that the resulting problems can be
      efficiently solved by the matrix scaling algorithm. Extensive experiments on
      eight datasets with different classifiers and performance measures show the
      effectiveness and generality of the proposed distances.

PMID- 30235118
TI  - Capturing the Geometry of Object Categories from Video Supervision.
AB  - In this article, we are interested in capturing the 3D geometry of object
      categories simply by looking around them. Our unsupervised method fundamentally
      departs from traditional approaches that require either CAD models or manual
      supervision. It only uses video sequences capturing a handful of instances of an
      object category to train a deep architecture tailored for extracting 3D geometry
      predictions. Our deep architecture has three components. First, a Siamese
      viewpoint factorization network robustly aligns the input videos and, as a
      consequence, learns to predict the absolute category-specific viewpoint from a
      single image depicting any previously unseen instance of that category. Second, a
      depth estimation network performs monocular depth prediction. Finally, a 3D shape
      completion network predicts the full shape of the depicted object instance by re
      using the output of the monocular depth prediction module. We also propose a way
      to configure networks so they can perform probabilistic predictions. We
      demonstrate that, properly used in our framework, this self-assessment mechanism
      is crucial for obtaining high quality predictions. Our network achieves state-of
      the-art results on viewpoint prediction, depth estimation, and 3D point cloud
      estimation on public benchmarks.

PMID- 30235119
TI  - Scan-time Corrections for 80-100 Minute Standardized Uptake Volume Ratios to
      Measure the 18F-AV-1451 Tracer for Tau Imaging.
AB  - The 18F-AV-1451 PET tracer binds to tau, an Alzheimer's Disease (AD) biomarker.
      The standardized uptake value ratio (SUVR) 80-100 min window is widely used to
      quantify tau binding, although 18F-AV-1451 continues increasing relative to a
      reference region in regions with tau deposition. Left uncorrected, acquisition
      time inaccuracies can lead to errors from -4% to 6% in 20-min SUVR measurements
      in subjects with Alzheimer's Disease. In 40 subjects with scans from 75-115 min
      following 18F-AV-1451 injection, we created 20-min reconstructions (4*5 min) of
      start-times ranging from 75-85 min, as proxies of offset scans and calculated the
      mean in regions of interest (ROIs). We developed a Segmented Least Squares (SLS)
      method to obtain error-minimizing weighting coefficients for 18F-AV-1451 ROIs
      that best predict SUVR 80-100 from weighted means of SUVRs from offset start
      times. We compared residual errors of our SLS method to those in (1) uncorrected
      offset 20-min-SUVRs, (2) the mean of 5-min frames within the 80-100 window, and
      (3) a least-squares interpolation method. We evaluated errors induced by start
      time offset on SUVRs for each method. SLS, which corrected using least-squares
      coefficients of 5-min components, consistently reduced errors across all offset
      start-times. Effect size analysis for simulated clinical longitudinal 18F-AV-1451
      drug trials showed that uncorrected 20-min offset SUVRs would require up to 20%
      more participants to detect treatment effects compared to using SLS. Correction
      of SUVR scan-time errors by SLS minimizes errors compared to other correction
      methods and may be extended to other scanners and tracers.

PMID- 30235120
TI  - A Sparse Non-negative Matrix Factorization Framework for Identifying Functional
      Units of Tongue Behavior from MRI.
AB  - Muscle coordination patterns of lingual behaviors are synergies generated by
      deforming local muscle groups in a variety of ways. Functional units are
      functional muscle groups of local structural elements within the tongue that
      compress, expand, and move in a cohesive and consistent manner. Identifying the
      functional units using tagged-Magnetic Resonance Imaging (MRI) sheds light on the
      mechanisms of normal and pathological muscle coordination patterns, yielding
      improvement in surgical planning, treatment, or rehabilitation procedures. Here,
      to mine this information, we propose a matrix factorization and probabilistic
      graphical model framework to produce building blocks and their associated
      weighting map using motion quantities extracted from tagged-MRI. Our tagged-MRI
      imaging and accurate voxel-level tracking provide previously unavailable internal
      tongue motion patterns, thus revealing the inner workings of the tongue during
      speech or other lingual behaviors. We then employ spectral clustering on the
      weighting map to identify the cohesive regions defined by the tongue motion that
      may involve multiple or undocumented regions. To evaluate our method, we perform
      a series of experiments. We first use two-dimensional images and synthetic data
      to demonstrate the accuracy of our method. We then use three-dimensional
      synthetic and in vivo tongue motion data using protrusion and simple speech tasks
      to identify subject-specific and data-driven functional units of the tongue in
      localized regions.

PMID- 30235121
TI  - Robust Optical Flow Estimation in Cardiac Ultrasound Images Using a Sparse
      Representation.
AB  - This paper introduces a robust 2D cardiac motion estimation method. The problem
      is formulated as an energy minimization with an optical flow-based data fidelity
      term and two regularization terms imposing spatial smoothness and sparsity of the
      motion field in an appropriate cardiac motion dictionary. Robustness to outliers,
      such as imaging artefacts and anatomical motion boundaries, is introduced using
      robust weighting functions for the data fidelity term as well as for the spatial
      and sparse regularizations. The motion fields and the weights are computed
      jointly using an iteratively re-weighted minimization strategy. The proposed
      robust approach is evaluated on synthetic data and realistic simulation sequences
      with available ground-truth by comparing the performance with state-of-the-art
      algorithms. Finally, the proposed method is validated using two sequences of in
      vivo images. The obtained results show the interest of the proposed approach for
      2D cardiac ultrasound imaging.

PMID- 30235122
TI  - A Convergence Proof of MLEM and MLEM-3 with Fixed Background.
AB  - Maximum Likelihood Expectation-Maximization (MLEM) is a popular algorithm to
      reconstruct the activity image in Positron Emission Tomography (PET). This paper
      introduces a 'fundamental equality' for the MLEM complete data from which two key
      properties easily follow that allows us to: (i) prove in an elegant and compact
      way the convergence of MLEM for a forward model with fixed background (i.e.,
      counts such as random and scatter coincidences); and (ii) generalize this proof
      for the MLEM-3 algorithm. Moreover we give necessary and sufficient conditions
      for the solution to be unique.

PMID- 30235123
TI  - Automated quantification of bileaflet mechanical heart valve leaflet angles in CT
      images.
AB  - Cardiac computed tomography (CT) is a valuable tool for functional mechanical
      heart valve (MHV) assessment. An important aspect of bileaflet MHV assessment is
      evaluation and measurement of leaflet opening and closing angles. Performed
      manually however, it is a laborious and time consuming task. In this paper, we
      propose an automated approach for bileaflet MHV leaflet angle computation. This
      method consists of four steps. After a one click selection of the MHV region on
      an axial image, an automatic MHV extraction using thresholding and connected
      component analysis based on voxel intensities is performed. Then the MHV
      component (valve ring and two leaflets) positions are identified using random
      sample consensus and least square fitting. Finally, the angles are automatically
      computed based on the orientation of the components in each timeframe. Five
      multiphase CT scans from patients with a bileaflet MHV containing between 14 and
      17 timepoints were used for development and another fifteen were used for
      evaluation. The detected MHV components were scored for their overlap with real
      components as successful or unsuccessful. For successful results, the angles were
      compared to those measured by a radiologist. Qualitatively evaluated on a dataset
      of 222 images, a total of 398 out of 444 angle computations (89.6%) were rated as
      successful. Compared to the angles measured by the radiologist, the successful
      angles showed a mean difference of 0.54 degrees  +/- 3.63 degrees  from the
      manual calculations. The method provides a high success rate and an accurate
      computation of leaflet opening angles compared to manual measurements.

PMID- 30235124
TI  - Experimental Investigation of Surface Acoustic Wave Acoustoelectric Effect Using
      a Graphene Film on Lithium Niobate.
AB  - Experimental results of the measured surface acoustic wave (SAW) acoustoelectric
      effect (AE) using single-layer thin-film graphene on 128 degrees , -cut, and 
      propagating lithium niobate (128-LN) are presented. The use of an AE amplifier in
      SAW communication devices, especially in gigahertz bands, could make fundamental
      advancements in radios, sensors, and other applications. Experimental results at
      1350 MHz show the delay line asymmetry of 3 dB, given as the ratio of the forward
      versus reverse peak SAW frequency response, with an applied dc voltage on the
      graphene film.

PMID- 30235125
TI  - Uncertainty evaluation of an 171Yb optical lattice clock at NMIJ.
AB  - We report an uncertainty evaluation of an 171Yb optical lattice clock with a
      total fractional uncertainty of 3.6 * 10-16, which is mainly limited by the
      lattice-induced light shift and the blackbody radiation shift. Our evaluation of
      the lattice-induced light shift, the density shift, and the secondorder Zeeman
      shift is based on an interleaved measurement where we measure the frequency shift
      using the alternating stabilization of a clock laser to the 6s2 1S0 - 6s6p 3P0
      clock transition with two different experimental parameters. In the present
      evaluation, the uncertainties of two sensitivity coefficients for the lattice
      induced hyperpolarizability shift d incorporated in a widely-used light shift
      model by RIKEN and the second-order Zeeman shift aZ are improved compared with
      the uncertainties of previous coefficients. The hyperpolarizability coefficient d
      is determined by investigating the trap potential depth and the light shifts at
      the lattice frequencies near the two-photon transitions 6s6p3P0 - 6s8p3P0,
      6s8p3P2, and 6s5f3F2. The obtained values are d = -1.1(4) MUHz and aZ = -6.6(3)
      Hz/mT2. These improved coefficients should reduce the total systematic
      uncertainties of Yb lattice clocks at other institutes.

PMID- 30235126
TI  - Rectification Using Different Types of Cameras Attached to a Vehicle.
AB  - The rectification process is a compulsory step in stereo matching computation. To
      obtain depth information, stereo camera systems are often installed in vehicles
      for outdoor and street-related applications, including vehicle and pedestrian
      detection, lane detection, and traffic sign recognition. In this paper, we
      propose a rectification method that uses currently available front- and rear-view
      vehicle cameras to produce rectified stereo images. The proposed method can be
      employed with different types of cameras that have varying focal lengths. In
      addition, this method tolerates the problem of camera alignment variation from
      normal stereo camera systems. To achieve this, a compensation method for
      different focal lengths and the estimation of image relationships are introduced.
      The experimental results demonstrate that the proposed method can operate
      robustly and accurately with different kinds of stereo images and significantly
      outperforms a state-of-the-art rectification method.

PMID- 30235127
TI  - Graph-Regularized Locality-Constrained Joint Dictionary and Residual Learning for
      Face Sketch Synthesis.
AB  - Face sketch synthesis is a crucial issue in digital entertainment and law
      enforcement. It can bridge the considerable texture discrepancy between face
      photos and sketches. Most of the current face sketch synthesis approaches
      directly to learn the relationship between the photos and sketches, and it is
      very difficult for them to generate the individual specific features, which we
      call rare characteristics. In this paper, we propose a novel face sketch
      synthesis approach through residual learning. In contrast to traditional
      approaches, which aim to reconstruct a sketch image directly (i.e., learn the
      mapping relationship between the photo and sketch), we aim to predict the
      residual image by learning the mapping relationship between the photo and
      residual, i.e., the difference between the photo and sketch, given an observed
      photo. This technique will render optimizing the residual mapping easier than
      optimizing the original mapping and deriving rare characteristic information. We
      also introduce a joint dictionary learning algorithm by preserving the local
      geometry structure of a data space. Through the learned joint dictionary, we
      transform the face sketch synthesis from an image space to a new and compact
      space; the new and compact space is spanned by learned dictionary atoms, where
      the manifold assumption can be further guaranteed. Results show that the proposed
      method demonstrates an impressive performance in the face sketch synthesis task
      on three public face sketch datasets and various real-world photos. These results
      are derived by comparing the proposed method with several state-of-the-art
      techniques, including certain recently proposed deep learning-based approaches.

PMID- 30235128
TI  - Kernel Distance Metric Learning Using Pairwise Constraints for Person Re
      Identification.
AB  - Person re-identification is a fundamental task in many computer vision and image
      understanding systems. Due to appearance variations from different camera views,
      person re-identification still poses an important challenge. In the literature,
      KISSME has already been introduced as an effective distance metric learning
      method using pairwise constraints to improve the re-identification performance.
      Computationally, it only requires two inverse covariance matrix estimations.
      However, the linear transformation induced by KISSME is not powerful enough for
      more complex problems. We show that KISSME can be kernelized, resulting in a
      nonlinear transformation, which is suitable for many real-world applications.
      Moreover, the proposed kernel method can be used for learning distance metrics
      from structured objects without having a vectorial representation. The
      effectiveness of our method is validated on five publicly available data sets. To
      further apply the proposed kernel method efficiently when data are collected
      sequentially, we introduce a fast incremental version that learns a dissimilarity
      function in the feature space without estimating the inverse covariance matrices.
      The experiments show that the latter variant can obtain competitive results in a
      computationally efficient manner.

PMID- 30235129
TI  - Low-Rank Transfer Human Motion Segmentation.
AB  - Human motion segmentation has great potential in real world applications.
      Conventional segmentation approaches cluster data with no guidance from prior
      knowledge, which could easily cause unpredictable segmentation output and
      decrease the performance. To this end, we seek to improve the humanmotion
      segmentation performance by fully utilizing pre-existing well-labeled source
      data. Specifically, we design a new transfer subspace clustering method for
      motion segmentation with a weighted rank constraint. Specifically, our proposed
      model obtains representations of both source and target sequences by mitigating
      their distribution divergence, which allows for more effective knowledge transfer
      to the target. To guide new representation learning, we designed a novel
      sequential graph to preserve temporal information residing in both the source and
      target. Furthermore, a weighted low-rank constraint is added to enforce the graph
      regularizer and uncover clustering structures within data. Experiments are
      evaluated on four human motion databases, which prove the enhanced performance
      and increased stability of our model compared to state-of-the-art baselines.

PMID- 30235130
TI  - Dynamic Feature Matching for Partial Face Recognition.
AB  - Partial face recognition (PFR) in an unconstrained environment is a very
      important task, especially in situations where partial face images are likely to
      be captured due to occlusions, out-of-view, and large viewing angle, e.g., video
      surveillance and mobile devices. However, little attention has been paid to PFR
      so far and thus, the problem of recognizing an arbitrary patch of a face image
      remains largely unsolved. This study proposes a novel partial face recognition
      approach, called Dynamic Feature Matching (DFM), which combines Fully
      Convolutional Networks (FCNs) and Sparse Representation Classification (SRC) to
      address partial face recognition problem regardless of various face sizes. DFM
      does not require prior position information of partial faces against a holistic
      face. By sharing computation, the feature maps are calculated from the entire
      input image once, which yields a significant speedup. Experimental results
      demonstrate the effectiveness and advantages of DFM in comparison with state-of
      the-art PFR methods on several partial face databases, including CAISA-NIR
      Distance, CASIA-NIR-Mobile, and LFW databases. The performance of DFM is also
      impressive in partial person re-identification on Partial RE-ID and iLIDS
      databases. The source code of DFM can be found at https://github.com/lingxiao
      he/dfm new.

PMID- 30235131
TI  - Fast Adaptive Bilateral Filtering.
AB  - In the classical bilateral filter, a fixed Gaussian range kernel is used along
      with a spatial kernel for edge-preserving smoothing. We consider a generalization
      of this filter, the so-called adaptive bilateral filter, where the center and
      width of the Gaussian range kernel are allowed to change from pixel to pixel.
      Though this variant was originally proposed for sharpening and noise removal, it
      can also be used for other applications, such as artifact removal and texture
      filtering. Similar to the bilateral filter, the brute-force implementation of its
      adaptive counterpart requires intense computations. While several fast algorithms
      have been proposed in the literature for bilateral filtering, most of them work
      only with a fixed range kernel. In this paper, we propose a fast algorithm for
      adaptive bilateral filtering, whose complexity does not scale with the spatial
      filter width. This is based on the observation that the concerned filtering can
      be performed purely in range space using an appropriately defined local
      histogram. We show that by replacing the histogram with a polynomial and the
      finite range-space sum with an integral, we can approximate the filter using
      analytic functions. In particular, an efficient algorithm is derived using the
      following innovations: the polynomial is fitted by matching its moments to those
      of the target histogram (this is done using fast convolutions), and the analytic
      functions are recursively computed using integration-by-parts. Our algorithm can
      accelerate the brute-force implementation by at least , without perceptible
      distortions in the visual quality. We demonstrate the effectiveness of our
      algorithm for sharpening, JPEG deblocking, and texture filtering.

PMID- 30235132
TI  - Interactive obstruction-free lensing for volumetric data visualization.
AB  - Occlusion is an issue in volumetric visualization as it prevents direct
      visualization of the region of interest. While many techniques such as transfer
      functions, volume segmentation or view distortion have been developed to address
      this, there is still room for improvement to better support the understanding of
      objects' vicinity. However, most existing Focus+Context fail to solve partial
      occlusion in datasets where the target and the occluder are very similar density
      wise. For these reasons, we investigate a new technique which maintains the
      general structure of the investigated volumetric dataset while addressing
      occlusion issues. With our technique, the user interactively defines an area of
      interest where an occluded region or object is partially visible. Then our lens
      starts pushing at its border occluding objects, thus revealing hidden volumetric
      data. Next, the lens is modified with an extended field of view (fish-eye
      deformation) to better see the vicinity of the selected region. Finally, the user
      can freely explore the surroundings of the area under investigation within the
      lens. To provide real-time exploration, we implemented our lens using a GPU
      accelerated ray-casting framework to handle ray deformations, local lighting, and
      local viewpoint manipulation. We illustrate our technique with five application
      scenarios in baggage inspection, 3D fluid flow visualization, chest radiology,
      air traffic planning, and DTI fiber exploration.

PMID- 30235133
TI  - Visual Analytics for Topic Model Optimization based on User-Steerable Speculative
      Execution.
AB  - To effectively assess the potential consequences of human interventions in model
      driven analytics systems, we establish the concept of speculative execution as a
      visual analytics paradigm for creating user-steerable preview mechanisms. This
      paper presents an explainable, mixed-initiative topic modeling framework that
      integrates speculative execution into the algorithmic decisionmaking process. Our
      approach visualizes the model-space of our novel incremental hierarchical topic
      modeling algorithm, unveiling its inner-workings. We support the active
      incorporation of the user's domain knowledge in every step through explicit model
      manipulation interactions. In addition, users can initialize the model with
      expected topic seeds, the backbone priors. For a more targeted optimization, the
      modeling process automatically triggers a speculative execution of various
      optimization strategies, and requests feedback whenever the measured model
      quality deteriorates. Users compare the proposed optimizations to the current
      model state and preview their effect on the next model iterations, before
      applying one of them. This supervised human-in-the-loop process targets maximum
      improvement for minimum feedback and has proven to be effective in three
      independent studies that confirm topic model quality improvements.

PMID- 30235134
TI  - Augmented Reality Interface Design Approaches for Goal-directed and Stimulus
      driven Driving Tasks.
AB  - The automotive industry is rapidly developing new in-vehicle technologies that
      can provide drivers with information to aid awareness and promote quicker
      response times. Particularly, vehicles with augmented reality (AR) graphics
      delivered via head-up displays (HUDs) are nearing mainstream commercial
      feasibility and will be widely implemented over the next decade. Though AR
      graphics have been shown to provide tangible benefits to drivers in scenarios
      like forward collision warnings and navigation, they also create many new
      perceptual and sensory issues for drivers. For some time now, designers have
      focused on increasing the realism and quality of virtual graphics delivered via
      HUDs, and recently have begun testing more advanced 3D HUD systems that deliver
      volumetric spatial information to drivers. However, the realization of volumetric
      graphics adds further complexity to the design and delivery of AR cues, and
      moreover, parameters in this new design space must be clearly and operationally
      defined and explored. In this work, we present two user studies that examine how
      driver performance and visual attention are affected when using fixed and
      animated AR HUD interface design approaches in driving scenarios that require top
      down and bottom-up cognitive processing. Results demonstrate that animated design
      approaches can produce some driving gains (e.g., in goal-directed navigation
      tasks) but often come at the cost of response time and distance. Our discussion
      yields AR HUD design recommendations and challenges some of the existing
      assumptions of world-fixed conformal graphic approaches to design.

PMID- 30235135
TI  - Equalizer 2.0 - Convergence of a Parallel Rendering Framework.
AB  - Developing complex, real world graphics applications which leverage multiple GPUs
      and computers for interactive 3D rendering tasks is a complex task. It requires
      expertise in distributed systems and parallel rendering in addition to the
      application domain itself. We present a mature parallel rendering framework which
      provides a large set of features, algorithms and system integration for a wide
      range of real-world research and industry applications. Using the Equalizer
      parallel rendering framework, we show how a wide set of generic algorithms can be
      integrated in the framework to help application scalability and development in
      many different domains, highlighting how concrete applications benefit from the
      diverse aspects and use cases of Equalizer. We present novel parallel rendering
      algorithms, powerful abstractions for large visualization setups and virtual
      reality, as well as new experimental results for parallel rendering and data
      distribution.

PMID- 30235137
TI  - P4: Portable Parallel Processing Pipelines for Interactive Information
      Visualization.
AB  - We present P4, an information visualization toolkit that combines declarative
      design specification and GPU computing for building high-performance interactive
      systems. Most of the existing information visualization toolkits do not harness
      the power of parallel processors in today's mainstream computers. P4 leverages
      GPU computing to accelerate both data processing and visualization rendering for
      interactive visualization applications. P4's programming interface offers a
      declarative visualization grammar for rapid specifications of data
      transformations, visual encodings, and interactions. By simplifying the
      development of GPU-accelerated visualization systems while supporting a high
      degree of flexibility and customization for design specification, P4 narrows the
      gap between expressiveness and scalability in information visualization toolkits.
      Through a range of examples and benchmark tests, we demonstrate that P4 provides
      high efficiency for creating interactive visualizations and offers drastic
      performance improvement over current state-of-the-art toolkits.

PMID- 30235136
TI  - FleXeen: Visually Manipulating Perceived Fabric Bending Stiffness in Spatial
      Augmented Reality.
AB  - It has been suggested that the appearance of fabric motion affects the human
      perception of its bending stiffness. This paper presents a novel spatial
      augmented reality (SAR), or projection mapping, approach that can visually
      manipulate the perceived bending stiffness of a fabric. In particular, we propose
      a flow enhancement method that changes apparent fabric motion based on a simple
      optical flow analysis technique rather than complex physical simulations for
      interactive applications. Through a psychophysical experiment, we investigated
      the relationship between the magnification factor of our flow enhancement and
      perceived bending stiffness of fabric. Furthermore, we constructed a prototype
      application system that allows a user to control the stiffness of a fabric
      without changing the actual physical fabric. Through an evaluation of the
      prototype, we confirmed that, on average, the proposed technique could manipulate
      the perceived stiffness for various materials (i.e., cotton, polyester, and mixed
      cotton and linen) at an average accuracy of 90.3%.

PMID- 30235138
TI  - AutoSweep: Recovering 3D Editable Objects from a Single Photograph.
AB  - This paper presents a fully automatic framework for extracting editable 3D
      objects directly from a single photograph. Unlike previous methods which recover
      either depth maps, point clouds, or mesh surfaces, we aim to recover 3D objects
      with semantic parts and can be directly edited. We base our work on the
      assumption that most human-made objects are constituted by parts and these parts
      can be well represented by generalized primitives. Our work makes an attempt
      towards recovering two types of primitive-shaped objects, namely, generalized
      cuboids and generalized cylinders. To this end, we build up a novel instance
      aware segmentation network for accurate part separation. Our GeoNet outputs a set
      of smooth part-level masks labeled as profiles and bodies. Then in a key stage,
      we simultaneously identify profile-body relations and recover 3D parts by
      sweeping the recognized profile along their body contour and jointly optimize the
      geometry to align with the recovered masks. Qualitative and quantitative
      experiments show that our algorithm can recover high quality 3D models and
      outperforms existing methods in both instance segmentation and 3D reconstruction.

PMID- 30235139
TI  - Unbiased Estimation of Human Joint Intrinsic Mechanical Properties During
      Movement.
AB  - The overall mechanical properties of a joint are generated by a combination
      intrinsic (mechanical) and reflex (neural) mechanisms. Nevertheless, many methods
      for estimating joint mechanical properties have used a linear dynamic model whose
      parameters are commonly related to the joint inertial and visco-elastic
      properties. Such mechanical models cannot account for torques due to reflex
      mechanisms and consequently fitting them to data containing reflex torques can
      give biased results. This paper addresses this issue in two ways. First, using
      simulation studies, it demonstrates that fitting linear dynamic models in the
      presence of reflex torques will indeed provide biased estimates of intrinsic
      joint properties; the bias is significant for small reflex torques and increases
      proportionally with reflex torque magnitude. Second, it develops and validates a
      novel approach to accurately estimate the time-varying, intrinsic mechanical
      properties of a joint in the presence of reflex torques. The approach involves
      applying small position perturbations to the joint trajectory and then applying
      novel mathematical models and system identification techniques to analytically
      separate the measured total joint torque into its intrinsic and reflex
      components. The method first estimates a non-parametric, reflex electromyography
      torque model, and uses it to predict the reflex torques which is subtracted from
      the total torque. Then, it estimates a non-parametric, linear, and time-varying
      model of the intrinsic mechanical properties from the residuals. Simulation
      results demonstrate that the new approach accurately tracks time-varying joint
      intrinsic mechanical properties during movement independently of the reflex
      torque magnitude. The new algorithm will be a useful tool in the study of motor
      control, as it supports the unbiased estimation of joint intrinsic mechanical
      properties during movement in the presence of reflex torques.

PMID- 30235141
TI  - Cardiac Conduction Model for Generating 12 Lead ECG Signals With Realistic Heart
      Rate Dynamics.
AB  - We present an extended heterogeneous oscillator model of cardiac conduction
      system for generation of realistic 12 lead ECG waveforms. The model consists of
      main natural pacemakers represented by modified van der Pol equations, and atrial
      and ventricular muscles, in which the depolarization and repolarization processes
      are described by modified FitzHugh-Nagumo equations. We incorporate an artificial
      RR-tachogram with the specific statistics of a heart rate, the frequency-domain
      characteristics of heart rate variability produced by Mayer and respiratory sinus
      arrhythmia waves, normally distributed additive noise and a baseline wander that
      couple the respiratory frequency. The standard 12 lead ECG is calculated by means
      of a weighted linear combination of atria and ventricle signals and thus can be
      fitted to clinical ECG of real subject. The model is capable to simulate
      accurately realistic ECG characteristics including local pathological phenomena
      accounting for biophysical properties of the human heart. All these features
      provide significant advantages over existing nonlinear cardiac models. The
      proposed model constitutes a useful tool for medical education and for assessment
      and testing of ECG signal processing software and hardware systems.

PMID- 30235140
TI  - An Untethered Ankle Exoskeleton Improves Walking Economy in a Pilot Study of
      Individuals With Cerebral Palsy.
AB  - The high energy cost of walking in individuals with cerebral palsy (CP)
      contributes significantly to reduced mobility and quality of life. The purpose of
      this paper was to develop and clinically evaluate an untethered ankle exoskeleton
      with the ability to reduce the metabolic cost of walking in children and young
      adults with gait pathology from CP. We designed a battery-powered device
      consisting of an actuator-and-control module worn above the waist with a Bowden
      cable transmission used to provide torque to pulleys aligned with the ankle.
      Special consideration was made to minimize adding mass to the body, particularly
      distal portions of the lower-extremity. The exoskeleton provided plantar-flexor
      assistance during the mid-to-late stance phase, controlled using a real-time
      control algorithm and embedded sensors. We conducted a device feasibility and a
      pilot clinical evaluation study with five individuals with CP ages five through
      thirty years old. Participants completed an average of 130 min of exoskeleton
      assisted walking practice. We observed a 19+/-5% improvement in the metabolic
      cost of transport (p = 0.011) during walking with untethered exoskeleton
      assistance compared to how participants walked normally. These preliminary
      findings support the future investigation of powered ankle assistance for
      improving mobility in this patient population.

PMID- 30235142
TI  - NetADD: Network Flow-Based Distributed Topology Control on Addressing Asymmetric
      Data Delivery in Nanonetworks.
AB  - Architecting nanonetwork-based coronary heart disease monitoring requires a set
      of nanodevice-embedded drug-eluting stents (nanoDESs) inserted inside the
      affected sites of coronary arteries of the heart to cooperatively collect medical
      information therein and transmit the information via the nano-macro (NM)
      interface, which is inserted into the intercostal space of the rib cage. These
      nanonetworks, which operate in the terahertz band (0.1-10 THz), face increased
      complexity in delivering the data of underlying nanonetworks to the NM, due to
      the limited energy content of nanoDESs. In this paper, we propose a distributed
      topology control algorithm based on the solution of the well-known network flow
      problem for addressing asymmetric data delivery. The generated topology is
      dynamic in the sense that it changes according to the energy levels of the
      nanoDESs. The proposed algorithm helps establish the topology and balance the
      load on nanoDESs. The proposed approach changes the topology if there arises a
      need to balance the energy content of the nanoDESs. We study the problem of
      asymmetric data delivery in various types of network topologies as well. The
      proposed solution is shown via extensive simulation to yield improved performance
      over the existing topology control solutions with respect to data delivery ratio,
      energy consumption, delay, and the events of shutdown.

PMID- 30235143
TI  - Mutual Information and Maximum Achievable Rate for Mobile Molecular Communication
      Systems.
AB  - Molecular communication (MC) enables conveying information at nano- to micro
      scales via molecules or nanoscale particles. MC systems for fixed transmitter and
      receiver nanomachines have been extensively investigated. However, the scenarios
      for mobile MC are seldomly studied. In the paper, the mutual information and
      achievable rate in the presence of inter-symbol interference and noise for the
      mobile MC is investigated. The scenario that both the transmitter and the
      receiver are in independent random motions is considered. Due to the mobility,
      the channel impulse response varies and results in a varying received signal with
      varying signal-dependent noise. This further leads to the random variation of the
      probability density functions of received concentration for symbols which further
      generates varying error probability and therefore varying mutual information and
      maximum achievable rate. In this paper, the mutual information and maximum
      achievable rate for mobile MC scenario are derived and analyzed. The impacts of
      different parameters, such as the initial transmitter-receiver distance, the
      number of released molecules, symbol interval, the mobility of nanomachine, and
      priori probabilities of the transmitted symbol on the mutual information and
      maximum achievable rate in mobile MC scenario are studied by simulation
      investigations.

PMID- 30235144
TI  - Biological Optical-to-Chemical Signal Conversion Interface: A Small-scale
      Modulator for Molecular Communications.
AB  - Although many exciting applications of molecular communication (MC) systems are
      envisioned to be at microscale, the MC testbeds reported in the literature so far
      are mostly at macroscale. This may partially be due to the fact that controlling
      an MC system at microscale is challenging. To link the macroworld to the
      microworld, we propose and demonstrate a biological signal conversion interface
      that can also be seen as a microscale modulator. In particular, the proposed
      interface transduces an optical signal, which is controlled using a lightemitting
      diode (LED), into a chemical signal by changing the pH of the environment. The
      modulator is realized using Escherichia coli bacteria as microscale entity
      expressing the light-driven proton pump gloeorhodopsin from Gloeobacter
      violaceus. Upon inducing external light stimuli, these bacteria locally change
      their surrounding pH level by exporting protons into the environment. To verify
      the effectiveness of the proposed optical-to-chemical signal converter, we
      analyze the pH signal measured by a pH sensor, which serves as receiver. We
      develop an analytical parametric model for the induced chemical signal as a
      function of the applied optical signal. Using this model, we derive a
      trainingbased channel estimator which estimates the parameters of the proposed
      model to fit the measurement data based on a least square error approach. We
      further derive the optimal maximum likelihood detector and a suboptimal low
      complexity detector to recover the transmitted data from the measured received
      signal. It is shown that the proposed parametric model is in good agreement with
      the measurement data. Moreover, for an example scenario, we show that the
      proposed setup is able to successfully convert an optical signal representing a
      sequence of binary symbols into a chemical signal with a bit rate of 1 bit/min
      and recover the transmitted data from the chemical signal using the proposed
      estimation and detection schemes. The proposed modulator may form the basis for
      future MC testbeds and applications at microscale.

PMID- 30235145
TI  - Molecular Communications Pulse-Based Jamming Model for Bacterial Biofilm
      Suppression.
AB  - Studies have recently shown that the bacteria survivability within biofilms is
      responsible for the emergence of superbugs. The combat of bacterial infections,
      without enhancing its resistance to antibiotics, includes the use of
      nanoparticles to quench the quorum sensing of these biofilm-forming bacteria.
      Several sequential and parallel multi-stage communication processes are involved
      in the formation of biofilms. In this paper, we use proteomic data from a wet lab
      experiment to identify the communication channels that are vital to these
      processes. We also identified the main proteins from each channel and propose the
      use of jamming signals from synthetically engineered bacteria to suppress the
      production of those proteins. This biocompatible technique is based on synthetic
      biology and enables the inhibition of biofilm formation. We analyze the
      communications performance of the jamming process by evaluating the path loss for
      a number of conditions that include different engineered bacterial population
      sizes, distances between the populations, and molecular signal power. Our results
      show that sufficient molecular pulse-based jamming signals are able to prevent
      the biofilm formation by creating lossy communications channels (almost -3 dB for
      certain scenarios). From these results, we define the main design parameters to
      develop a fully operational bacteria-based jamming system.

PMID- 30235146
TI  - Algorithm and VLSI Architecture Design of Low-Power SPIHT Decoder for mHealth
      Applications.
AB  - A real-time cost and power-efficient (CPE) set partitioning in hierarchical trees
      (SPIHT) decoder design with low hardware complexity and low-power dissipation is
      introduced in one-dimension (1-D) wavelet-based quality-assured
      electrocardiograph (ECG) compression systems for mobile health (mHealth)
      applications. However, current SPIHT coding architectures are designed for
      image/video processing. These architectures require a large amount of memory as
      well as complicated sorting algorithms, which both require time-consuming tasks
      and are unsuitable for mobile ECG applications. Based on our previously modified
      SPIHT coding work, which used flags and check bits to reduce memory requirements
      and coding complexity by merging three search processes into one step. Therefore,
      to achieve the real-time design goal for mobile ECG applications, in this paper,
      we first introduce a hardware-oriented SPIHT decoding algorithm that is suitable
      for decoding the previously presented SPIHT coding work. Accordingly, an
      appropriate low-power hardware architecture is developed to implement a real-time
      high-performance and low-cost SPIHT VLSI design for our proposed decoder
      algorithm, which is appropriate for mobile ECG applications. Using the distinct
      ECG signals in the MIT-BIH arrhythmia database (sampling rate of 640 Hz), the
      final simulation and VLSI implementation results reveal that the proposed CPE
      SPIHT decoder design outperforms the state-of-the-art designs in terms of the
      average decoding time, the decoding quality, the VLSI speed, and the power
      consumption. Most importantly, the design can be exploited to a 1-D 1024 * 1
      wavelet-based quality-assured ECG data compression system.

PMID- 30235148
TI  - Signal Loss Compensation of RF Crossbar Switch Matrix System in Ultra-High Field
      MRI.
AB  - With the increased commercial availability of high channel count MR coil arrays
      and the associated higher number of plugs in the patient bed, it has become
      common practice to include switch matrices in the receive path of MR systems.
      These allow the arbitrary routing of a signal from any plug to any receiver in
      the console. While switch matrices are standard in systems at clinical field
      strength and have been developed for systems operating up to 4T, they have not
      yet been implemented at ultra-high field (UHF). Here we present a switch matrix
      suitable for operation at UHF. Crossbar switches, which are the most frequently
      employed forms of a switch matrix, use RF switches to connect horizontal input
      lines with the desired vertical output line. This leaves transmission line stubs
      of variable length physically connected with the selected signal path,
      potentially resulting in elevated signal losses. While this can be tolerated at
      low frequencies, and only needs partial compensation at intermediate frequencies
      (4T), a full compensation is required at UHF. In this study an RF crossbar
      switch, which uses switchable compensation elements in both horizontal and
      vertical transmission lines, was implemented for a 9.4T MRI scanner. The
      prototype developed was evaluated for single channel and multi-channel receive
      performance and benchmarked against a fixed wire connection.

PMID- 30235147
TI  - End-to-End Design of Efficient Ultrasonic Power Links for Scaling Towards
      Submillimeter Implantable Receivers.
AB  - We present an analytical framework for optimizing the efficiency of ultrasonic
      wireless power links for implantable devices scaled down to sub-mm dimensions.
      Key design insights and tradeoffs are considered for various parameters including
      the operating frequency, the transmission depth, the size of the transmitter, the
      impedance and the aperture efficiency of the miniaturized receiver, and the
      interface between the receiver and the power recovery chain on the implant. The
      performance of spherically focused transducers as ultrasonic transmitters is
      analyzed to study the limits and the tradeoffs. Two optimization methods are
      presented: "Focal Peak" sets the focus of transducers at target depths, and
      "Global Maximum" maximizes the efficiency globally with off-focus operation. The
      results are also compared to phased array implementations. To investigate the
      efficiency of implants, miniaturized receivers made from single crystalline
      piezoelectric material, PMN-PT, are used as they have resonances in the derived
      optimal carrier frequency range (~1-2 MHz). A methodology to achieve an efficient
      interface to the power electronics is then provided using an optogenetic
      stimulator as an example platform. The analytical results are verified through
      both simulations and measurements. Finally, an example ultrasonic link using a
      spherical transmitter with a radius of 2 cm is demonstrated; link efficiencies of
      1.93-0.23% are obtained at 6-10 cm depths with sub-mm receivers for the
      optogenetic application.

PMID- 30235149
TI  - Level-set Segmentation based Respiratory Volume Estimation using Depth Camera.
AB  - In this paper, a method is proposed by which to measure human respiratory volume
      using a depth camera. The level-set segmentation method, combined with spatial
      and temporal information, was used to measure respiratory volume accurately. The
      shape of the human chest wall was used as spatial information. As temporal
      information, the segmentation result from the previous frame in the time-aligned
      depth image was used. The results of the proposed method were verified using a
      ventilator. The proposed method was also compared with other level-set methods.
      The result showed that the mean tidal volume error of the proposed method was
      8.41% compared to the actual tidal volume. This was calculated to be less error
      than with two other methods : the level-set method with spatial information
      (14.34%) and the level-set method with temporal information (10.93%). The
      difference between these methods of tidal volume error was statistically
      significant ($p ?lt 0.0001$). The intra-class correlation coefficient (ICC) of
      the respiratory volume waveform measured by a ventilator and by the proposed
      method was 0.893 on average, while the ICC between the ventilator and the other
      methods were 0.837 and 0.879 on average.

PMID- 30235150
TI  - A Continuously Updated, Computationally Efficient Stress Recognition Framework
      Using Electroencephalogram (EEG) by Applying Online Multi-Task Learning
      Algorithms (OMTL).
AB  - Recognizing the factors that cause stress is a crucial step toward early
      detection of stressors. In this regard, several studies make an effort to
      recognize individuals' stress using an Electroencephalogram (EEG). However,
      current EEG-based stress recognition frameworks have several drawbacks. First,
      they are mostly designed to recognize individuals' stress only in a controlled
      laboratory environment. Second, they do not take into account the changes in the
      EEG signals of different subjects under the same stressors. Third, most of the
      current stress recognition algorithms occur in an offline setting. To address
      these issues, this study proposes an EEG-based stress recognition framework that
      takes into account each subject's brainwave patterns to train the stress
      recognition classifier and continuously update its classifier based on new input
      signals in near real-time. The proposed framework first removes EEG signal
      artifacts, then extracts a broad range of EEG signal features, and finally
      applies different Online Multi-Task Learning (OMTL) algorithms to recognize
      individuals' stress in near real time. The proposed framework was applied on the
      EEG collected in two environments-first on the EEG collected in a controlled lab
      environment using a wired-EEG and second on the EEG collected at in the field
      using a wearable EEG device. The OMTL-VonNeuman method resulted in the best
      prediction accuracy on both datasets (71.14% on the first dataset and 77.61% on
      second) among all tested algorithms. The proposed stress recognition framework
      continuously updates its classifier and therefore contributes to stress
      recognition for new stressful situations that are beyond the range of pre-defined
      stressful conditions in near real time both in a controlled lab environment and
      at real job sites.

PMID- 30235151
TI  - Template-Based Statistical Modeling and Synthesis for Noise Analysis of
      Ballistocardiogram Signals: A Cycle-Averaged Approach.
AB  - OBJECTIVE: Ballistocardiogram (BCG) can be recorded using inexpensive and non
      invasive hardware to estimate physiological changes in the heart. In this work, a
      methodology is developed to evaluate the impact of additive noise on the BCG
      signal. METHODS: A statistical model is built that incorporates subject-specific
      BCG morphology. BCG signals segmented by ECG RR intervals (BCG heartbeats) are
      averaged to estimate a parent template and sub-templates leveraging the quasi
      periodic nature of the heart. Noise statistics are obtained for sub-templates
      with respect to the parent template. Then, a synthesis algorithm with adjustable
      additive noise is devised to generate sub-templates based on the individual's
      parent template and statistics. For the example use of the synthesis algorithm,
      the average correlation coefficient between sub-templates and the parent template
      (sub-template versus parent template approach) is tested as a signal quality
      index (SQI). RESULTS: A BCG heartbeat synthesis framework that incorporates an
      individual's BCG morphology, and physiological variability was developed to
      quantify variations in the BCG signal against additive noise. The signal quality
      assessment of a person's BCG recording could be performed without requiring any a
      priori knowledge on the person's BCG morphology. A data-driven constraint on the
      required minimum number of heartbeats for the reliable template estimation was
      provided. CONCLUSION: The impact of additive noise on BCG morphology and
      estimated physiological parameters can be analyzed using the developed
      methodology without requiring prior statistics. SIGNIFICANCE: This work can
      facilitate performance evaluation of BCG analysis algorithms against additive
      noise.

PMID- 30235152
TI  - Finite State Machine Framework for Instantaneous Heart Rate Validation using
      Wearable Photoplethysmography During Intensive Exercise.
AB  - Accurate estimation of heart rate (HR) using reflectance-type
      photoplethysmographic (PPG) signals during intensive physical exercise is
      challenging because of very low signal-to-noise ratio (SNR) and unpredictable
      motion artifacts (MAs), which are frequently uncorrelated with reference signals
      such as accelerometer signals. In this paper, we propose a finite state machine
      (FSM) framework based novel algorithm for HR estimation and validation, which
      exploits the crest factor from the periodogram obtained after MA removal, and the
      estimated HR changes in consecutive windows as the estimation accuracy
      indicators. Our proposed algorithm automatically provides only accurate HR
      estimation results in real-time by ignoring the estimation results when true HRs
      are not reflected in PPG signals or when the MAs uncorrelated with accelerometer
      signals are dominant. The performance of the HR estimation is rigorously compared
      with existing algorithms on the publicly available database of 23 PPG recordings
      measured during intensive physical exercise. Our algorithm exhibits an average
      absolute error of 0.99 beats per minute and an average relative error of 0.88%.
      The algorithm is simple; the computational time is $?le 1.2$ ms for 8s-window.
      Also, the algorithm framework can be combined with existing methods to improve
      estimation accuracy.

PMID- 30235153
TI  - Towards End-to-End ECG Classification with Raw Signal Extraction and Deep Neural
      Networks.
AB  - This paper proposes deep learning methods with signal alignment that facilitate
      the end-to-end classification of raw electrocardiogram (ECG) signals into
      heartbeat types, i.e., normal beat or different types of arrhythmias. Time-domain
      sample points are extracted from raw ECG signals, and consecutive vectors are
      extracted from a sliding time-window covering these sample points. Each of these
      vectors comprises the consecutive sample points of a complete heartbeat cycle,
      which includes not only the QRS complex but also the P and T waves. Unlike
      existing heartbeat classification methods in which medical doctors extract
      handcrafted features from raw ECG signals, the proposed end-to-end method
      leverages a deep neural network (DNN) for both feature extraction and
      classification based on aligned heartbeats. This strategy not only obviates the
      need to handcraft the features but also produces optimized ECG representation for
      heartbeat classification. Evaluations on the MIT-BIH arrhythmia database show
      that at the same specificity, the proposed patient-independent classifier can
      detect supraventricular- and ventricular-ectopic beats at a sensitivity that is
      at least 10% higher than current state-of-the-art methods. More importantly,
      there is a wide range of operating points in which both the sensitivity and
      specificity of the proposed classifier are higher than those achieved by state-of
      the-art classifiers. The proposed classifier can also perform comparable to
      patient-specific classifiers, but at the same time enjoys the advantage of
      patient independency.

PMID- 30235154
TI  - A Projection Neural Network for Identifying Copy Number Variants.
AB  - The identification of copy number variations (CNVs) helps the diagnosis of many
      diseases. One major hurdle in the path of CNVs discovery is that the boundaries
      of normal and aberrant regions cannot be distinguished from the raw data since
      various types of noise contaminate them. To tackle this challenge, the total
      variation regularization is mostly used in the optimization problems to
      approximate the noise-free data from corrupted observations. The minimization
      using such regularization is challenging to deal with since it is non
      differentiable. In this paper, we propose a projection neural network to solve
      the non-smooth problem. The proposed neural network has a simple one-layer
      structure and is theoretically assured to have the global exponential convergence
      to the solution of the total variation-regularized problem. The experiments on
      several real and simulated datasets illustrate the reasonable performance of the
      proposed neural network and show that its performance is comparable with those of
      more sophisticated algorithms.

PMID- 30235155
TI  - Containment Control for Discrete-Time Multiagent Systems With Communication
      Delays and Switching Topologies.
AB  - This paper studies a containment problem with communication delays and switching
      topologies. A nonlinear projection containment control algorithm for followers
      with single-integrator discrete-time dynamics is proposed. The main approach is
      to use the convexity of the convex hull spanned by multiple stationary leaders to
      show the nonincreasing monotonicity of the largest distance from the agents to
      the convex hull. It is shown that the nonlinear projection containment control
      algorithm is robust to arbitrarily bounded communication delays as long as each
      follower jointly has a path from some leaders to itself. Finally, a numerical
      example is implemented to show the obtained theoretical results.

PMID- 30235156
TI  - Feature Extraction for Classification of Hyperspectral and LiDAR Data Using Patch
      to-Patch CNN.
AB  - Multisensor fusion is of great importance in Earth observation related
      applications. For instance, hyperspectral images (HSIs) provide wealthy spectral
      information while light detection and ranging (LiDAR) data provide elevation
      information, and using HSI and LiDAR data together can achieve better
      classification performance. In this paper, an unsupervised feature extraction
      framework, named as patch-to-patch convolutional neural network (PToP CNN), is
      proposed for collaborative classification of hyperspectral and LiDAR data. More
      specific, a three-tower PToP mapping is first developed to seek an accurate
      representation from HSI to LiDAR data, aiming at merging multiscale features
      between two different sources. Then, by integrating hidden layers of the designed
      PToP CNN, extracted features are expected to possess deeply fused
      characteristics. Accordingly, features from different hidden layers are
      concatenated into a stacked vector and fed into three fully connected layers. To
      verify the effectiveness of the proposed classification framework, experiments
      are executed on two benchmark remote sensing data sets. The experimental results
      demonstrate that the proposed method provides superior performance when compared
      with some state-of-the-art classifiers, such as two-branch CNN and context CNN.

PMID- 30235157
TI  - Adaptive Fuzzy Tracking Control for Strict-Feedback Markov Jumping Nonlinear
      Systems With Actuator Failures and Unmodeled Dynamics.
AB  - In this paper, an adaptive fuzzy tracking controller is developed for a class of
      strict-feedback Markovian jumping systems subjected to multisource uncertainties.
      The unpredictable actuator failures, the unknown nonlinearities, and the
      unmodeled dynamics are simultaneously taken into consideration, which evolve
      according to the Markov chain. It is noted that the elements in the transition
      rate matrix of the Markov chain are not fully available. In virtue of the norm
      estimation approach, the challenges caused by the complex multiple uncertainties
      and actuator failures are effectively handled. Furthermore, to compensate for the
      unavailable switching nonlinearities, the fuzzy logic systems are employed as
      online approximators. As a result, a novel adaptive fuzzy fault-tolerant tracking
      control structure is constructed. The sufficient condition is provided to
      guarantee that the studied system is stochastically stable. Finally, a number of
      illustrative examples are employed to demonstrate the effectiveness of the
      proposed methodology.

PMID- 30235158
TI  - Immune-Endocrine System Inspired Hierarchical Coevolutionary Multiobjective
      Optimization Algorithm for IoT Service.
AB  - The intelligent devices in Internet of Things (IoT) not only provide services but
      also consider how to allocate heterogeneous resources and reduce resource
      consumption and service time as far as possible. This issue becomes crucial in
      the case of large-scale IoT environments. In order for the IoT service system to
      respond to multiple requests simultaneously and provide Pareto optimal decisions,
      we propose an immune-endocrine system inspired hierarchical coevolutionary
      multiobjective optimization algorithm (IE-HCMOA) in this paper. In IE-HCMOA, a
      multiobjective immune algorithm based on global ranking with vaccine is designed
      to choose superior antibodies. Meanwhile, we adopt clustering in top population
      to make the operations more directional and purposeful and realize self-adaptive
      searching. And we use the human forgetting memory mechanism to design two-level
      memory storage for the choice problem of solutions to achieve promising
      performance. In order to validate the practicability and effectiveness of IE
      HCMOA, we apply it to the field of agricultural IoT service. The simulation
      results demonstrate that the proposed algorithm can obtain the best Pareto, the
      strongest exploration ability, and excellent performance than nondominated
      neighbor immune algorithms and NSGA-II.

PMID- 30235159
TI  - Stability Analysis for Neural Networks With Time-Varying Delay via Improved
      Techniques.
AB  - This paper is concerned with the stability problem for neural networks with a
      time-varying delay. First, an improved generalized free-weighting-matrix integral
      inequality is proposed, which encompasses the conventional one as a special case.
      Second, an improved Lyapunov-Krasovskii functional is constructed that contains
      two complement triple-integral functionals. Third, based on the improved
      techniques, a new stability condition is derived for neural networks with a time
      varying delay. Finally, two widely used numerical examples are given to
      demonstrate that the proposed stability condition is very competitive in both
      conservatism and complexity.

PMID- 30235160
TI  - Event-Triggered Adaptive Output Feedback Control for a Class of Uncertain
      Nonlinear Systems With Actuator Failures.
AB  - This paper investigates the event-triggered adaptive output feedback control
      problem for a class of uncertain nonlinear systems in the presence of actuator
      failures and unknown control direction. By utilizing the adaptive backstepping
      technique, an event-based output feedback controller is developed together with a
      time-variant event-triggered rule. In this design, the radial basis function
      neural network algorithms are first introduced to identify the unknown terms of
      the systems. Then, a new state observer with adaptive compensation is designed to
      estimate the state vector. The overall control strategy guarantees that the
      output signal tracks the reference signal and all the signals of the closed-loop
      systems are bounded. Unlike the existing methods, the proposed control scheme can
      handle the coupling term incurred by the loss of effectiveness fault of the
      actuator, the event-triggered rule, and unknown control direction. Finally, an
      example is performed to demonstrate the validity of the proposed strategy.

PMID- 30235161
TI  - Type-2 Fuzzy Logic-Based Linguistic Pursuing Strategy Design and Its Deployment
      to a Real-World Pursuit Evasion Game.
AB  - This paper presents a systematic and interpretable design approach to generate
      type-2 (T2) fuzzy logic-based linguistic pursuing strategies (PSs) and their
      deployment to a real-world pursuit-evasion game (PEG). First, we have developed a
      novel T2 fuzzy logic-based strategy planner (T2-FSP). Then, through detailed
      theoretical investigations on the input-output mapping of the T2-FSP, it has been
      shown that it is possible to design a linguistic PS which defines both pursuer's
      approaching behavior (aggressive, smooth) and side (left or right) to the evader
      by simply tuning the footprint of uncertainty (FOU) sizes of the T2 fuzzy sets.
      Hence, an interpretable relationship has been revealed between the FOU sizes and
      the PSs through comparative theoretical explorations and derivations.
      Additionally, as there is a need to employ different PSs in a dynamic PEG
      environment, a type-1 fuzzy decision making (T1-FDM) mechanism has been designed
      to tune the FOU sizes of the T2-FSP and, thus, adjust the PS to be employed in
      real time. A real-world game environment is constructed in order to validate the
      developed T2 fuzzy logic-based PSs and T1-FDM mechanism in real time. Comparative
      experimental results have been presented to show that the T2 fuzzy logic-based
      PSs have satisfactory performance against a human user.

PMID- 30235162
TI  - Controllability Ensured Leader Group Selection on Signed Multiagent Networks.
AB  - Leader-follower controllability on signed multiagent networks is investigated in
      this paper. Specifically, we consider a dynamic signed multiagent network, where
      the agents interact via neighbor-based Laplacian feedback and the network allows
      positive and negative edges to capture cooperative and competitive interactions
      among agents. The agents are classified as either leaders or followers, thus
      forming a leader-follower signed network. To enable full control of the leader
      follower signed network, controllability ensured leader group selection
      approaches are investigated in this paper, that is, identifying a small subset of
      nodes in the signed network, such that the selected nodes are able to drive the
      network to a desired behavior, even in the presence of antagonistic interactions.
      In particular, graphical characterizations of the controllability of signed
      networks are first developed based on the investigation of the interaction
      between network topology and agent dynamics. Since signed path and cycle graphs
      are basic building blocks for a variety of networks, the developed topological
      characterizations are then exploited to develop leader selection methods for
      signed path and cycle graphs to ensure leader-follower controllability. Along
      with illustrative examples, heuristic algorithms are also developed showing how
      leader selection methods developed for path and cycle graphs can be potentially
      extended to more general signed networks. In contrast to existing results that
      mainly focus on unsigned networks, this paper characterizes controllability and
      develops leader selection methods for signed networks. In addition, the developed
      results are generic, in the sense that they are not only applicable to signed
      networks but also to unsigned networks, since unsigned networks are a particular
      case of signed networks that only contain positive edges.

PMID- 30235163
TI  - A Distributed Dynamic Event-Triggered Control Approach to Consensus of Linear
      Multiagent Systems With Directed Networks.
AB  - In this paper, we study the consensus problem for a class of linear multiagent
      systems, where the communication networks are directed. First, a dynamic event
      triggering mechanism is introduced, including some existing static event
      triggering mechanisms as its special cases. Second, based on the dynamic event
      triggering mechanism, a distributed control protocol is developed, which ensures
      that all agents can reach consensus with an exponential convergence rate. Third,
      it is shown that, with the dynamic event-triggering mechanism, the minimum
      interevent time between any two consecutive triggering instants can be prolonged
      and no agent exhibits Zeno behavior. Finally, an algorithm is provided to avoid
      continuous communication when the dynamic event-triggering mechanism is
      implemented. The effectiveness of the results is confirmed through a numerical
      example.

PMID- 30235164
TI  - On the relevance of symbolizing heart rate variability by means of a percentile
      based coarse graining approach.
AB  - OBJECTIVE: Symbolic transformations of the cardiac interbeat interval series
      yield a coarse-grained description of the dynamical information of the underlying
      system and complement standard measures of heart rate variability. The most
      commonly utilized coarse graining procedures are strongly influenced by the
      presence of a few extreme values wasting precious symbols to code very unlikely
      values. APPROACH: Here, we used a transformation procedure that ensured the
      appearance of each symbol with equal probability using a short alphabet, A 4  = 
      {0, 1, 2, 3}, and a long alphabet, A 6  =  {0, 1, 2, 3, 4, 5}. The procedure was
      applied to the cardiac interbeat interval series of 17 healthy subjects, obtained
      during graded head-up tilt tests at tilt table inclinations of 0 degrees , 15
      degrees , 30 degrees , 45 degrees , 60 degrees , 75 degrees , 90 degrees . The
      dynamics of the symbolic series was assessed by the rate of symbolic pattern
      categories. Symbolic patterns of length three were grouped according to the
      variations of the symbols in each pattern: no variation (0V%), one variation
      (1V%), two like variations (2LV%) and two unlike variations (2UV%) of the
      symbols. MAIN RESULTS: As for the alphabet A 4, the linear regression analysis on
      tilt angle showed that 0V% increased with increasing tilt angle whereas 1V%, 2LV%
      and 2UV% decreased. As for the alphabet A 6, the categories 0V%, and 1V%
      increased with increasing tilt angle whereas 2LV% and 2UV% decreased.
      SIGNIFICANCE: The symbolic transformation ensuring a uniform distribution of the
      symbols is capable of reflecting changes in the cardiac autonomic nervous system
      during graded head-up tilt. This approach is more robust against outliers and
      data with skewed distributions compared to previously used symbolizations.

PMID- 30235165
TI  - A convolutional neural network for ECG annotation as the basis for classification
      of cardiac rhythms.
AB  - OBJECTIVE: Electrocardiography is the most common tool to diagnose cardiovascular
      diseases. Annotation, segmentation and rhythm classification of ECGs are
      challenging tasks, especially in the presence of atrial fibrillation and other
      arrhythmias. Our aim is to increase the accuracy of heart rhythm estimation by
      the use of extreme gradient boosting trees and the development of a deep
      convolutional neural network for ECG segmentation. APPROACH: We trained a
      convolutional neural network with waveforms from PhysioNet databases to annotate
      QRS complexes, P waves, T waves, noise and interbeat ECG segments that
      characterize the essences of normal and irregular heart beats. We evaluated true
      positive rates, positive predictive values and mean absolute differences of our
      annotation based on reference annotations of the QT and MIT-BIH P-wave database.
      Moreover, we compared the results with standard QRS detectors and Ecgpuwave.
      Extreme gradient boosting trees were used to determine the heart rhythm based on
      hand-crafted features. More precisely, a noise estimation function was used in
      combination with heart rate and interval data. Furthermore we defined particular
      features based on ECG morphology, appearance of P waves and detection of
      irregular beats. We examined the feature importance and identified key features
      for normal sinus rhythm, atrial fibrillation, alternative rhythm and noisy
      recordings. The classification performance was evaluated externally using F 1
      scores by applying the algorithm to the hidden test set provided by the
      PhysioNet/CinC Challenge 2017. MAIN RESULTS: The true positive rate of the
      convolutional neural network in detection of manually revised R peaks in the QT
      database was [Formula: see text] and the positive predictive value was [Formula:
      see text]. The detection of P and T waves reached a true positive rate of
      [Formula: see text] and [Formula: see text] respectively, given a 50 ms tolerance
      when comparing the reference to the test annotation set. The rhythm
      classification performance reached an overall F 1 score of 0.82 when applying the
      algorithm to the hidden test set. SIGNIFICANCE: We achieved a shared rank #9 in
      the post-challenge phase of the PhysioNet/CinC Challenge 2017.

PMID- 30235166
TI  - The effects of asymmetric volume conductor modeling on non-invasive fetal ECG
      extraction.
AB  - OBJECTIVE: Non-invasive fetal electrocardiography (NI-FECG) shows promise for
      capturing novel physiological information that may indicate signs of fetal
      distress. However, significant deterioration in NI-FECG signal quality occurs
      during the presence of a highly non-conductive layer known as vernix caseosa
      which forms on the fetal body surface beginning in approximately the 28th week of
      gestation. This work investigates asymmetric modeling of vernix caseosa and other
      maternal-fetal tissues in accordance with clinical observations and assesses
      their impacts for NI-FECG signal processing. APPROACH: We develop a process for
      simulating dynamic maternal-fetal abdominal ECG mixtures using a synthetic
      cardiac source model embedded in a finite element volume conductor. Using this
      process, changes in NI-FECG signal morphology are assessed in an extensive set of
      finite element models including spatially variable distributions of vernix
      caseosa. MAIN RESULTS: Our simulations show that volume conductor asymmetry can
      result in over 70% error in the observed T/QRS ratio and significant changes to
      signal morphology compared to a homogeneous volume conductor model. Volume
      conductor effects must be considered when analyzing T/QRS ratios obtained via NI
      FECG and should be considered in future algorithm benchmarks using simulated
      data. SIGNIFICANCE: This work shows that without knowledge of the influence of
      volume conductor effects, clinical evaluation of the T/QRS ratio derived via NI
      FECG should be avoided.

PMID- 30235167
TI  - Alveolar Soft-Part Sarcoma of the Tongue.
AB  - Alveolar soft-part sarcoma is a rare neoplasm of unknown histogenesis that
      accounts for less than 1% of all soft-tissue sarcomas. The tumor is highly
      vascularized with small vascular spaces separating nests of cells, and from
      cytogenetic point of view, is characterized by chromosome rearrangement
      der(17)t(X:17)(p11:q25) that results in the ASPL-TFE3 translocation. It can occur
      at any age, but it is most common between 15 and 35 years of age. The prognosis
      is poor, despite the relatively slow growth of the tumor. We present here an
      atypical case of alveolar soft-part sarcoma in which the age of the patient, the
      location, and the histopathologic characteristics of the lesion represented a
      diagnostic challenge.

PMID- 30235168
TI  - Pretibial Lymphoplasmacytic Plaque in Children: Case Report and Review of the
      Literature.
AB  - An 8-year-old girl presented with a persistent 5 * 2-cm violaceous doughy plaque
      on the left lower leg. Histologic examination revealed hyperkeratosis, variable
      but mild epidermal hyperplasia, and vacuolar interface changes with melanin
      pigment incontinence confined to the papillary dermis. A diagnosis of pretibial
      lymphoplasmacytic plaque in children was made. This report outlines the clinical
      characteristics of this entity and a review of other cases reported in the
      literature.

PMID- 30235170
TI  - Vanishing Point.

PMID- 30235169
TI  - Acquired Dermal Melanocytosis Associated With Diffuse Systemic Sclerosis in a
      White Patient.
AB  - We report a case of a 65-year-old man who developed an asymptomatic bluish spot
      that affected the flank and left lumbar region with the onset 10 years prior. He
      had a history of diffuse systemic sclerosis with anti-Scl-70-positive antibodies.
      The appearance of the skin lesion coincided with the onset of his disease. The
      skin biopsy was consistent with the diagnosis of acquired dermal melanocytosis.
      The relationship between the appearance of acquired pigmented macules and spots
      and systemic sclerosis has been known for years, although it is an infrequent
      finding.

PMID- 30235171
TI  - Early Life Stress: a Key Link between Childhood Adversity and Risk of Attempting
      Suicide.
AB  - INTRODUCTION: Epidemiology shows that the major risk factors for suicide or
      attempting suicide are childhood adversities such as sexual and/or physical
      abuse, neglect, mental illness of caregiver, and family or community violence.
      Suicide, whether attempted or completed, is a significant social, financial and
      emotional burden worldwide. Identification of risk factors and antecedents
      predisposing individuals to increased risk of suicide is hence imperative so as
      to afford prompt and appropriate monitoring and intervention. AIM: Using
      epidemiological data from the Survey of adverse childhood experiences (ACE) among
      young people in the Republic of Macedonia to examine their association with
      suicide attempt and to discuss possible mechanisms within the 'stress biology
      research'. SUBJECTS AND METHODS: A representative sample consisted of total 1277
      students (58.6% female and 41.6%), aged 18 and above in year four of 664
      secondary school and 613 first- and second-year university students. The data
      were obtained using Adverse Childhood Experiences Study Questionnaires (Family
      Health History Questionnaire) for collecting information on child maltreatment,
      household dysfunction and other socio-behavioural factors, applying WHO/CDC
      recommended methodology. Statistical significance was set up at p<0.05. RESULTS:
      Emotional neglect, physical abuse and physical neglect were the most frequent
      abusive experiences students had. Overall, suicide attempts were reported by 3.1%
      of respondents (4.7% by females and 0.8% by males). Those respondents who had
      been emotionally abused were almost three times as likely to attempt suicide,
      physical abuse almost doubles the chances of attempting suicide, substance abuse
      in the family increased the chances 2.3 times for attempting suicide, violent
      treatment of the mother almost quadrupled them for attempted suicide, having a
      family member who had been in prison increased the odds of almost 3.5 times for
      attempting suicide. Attempted suicide was found to be 1.5 times more likely as
      the number of ACEs reaches 3 and 3.4 times more likely as the number of adverse
      childhood experiences reached four or more. CONCLUSIONS: Identifying and treating
      children, adolescents and young adults who have been affected by adverse
      childhood experiences may have substantial value in our evolving efforts to
      prevent suicide.

PMID- 30235172
TI  - Changing Diagnostic Category in Development Psychiatry.
AB  - INTRODUCTION: Many children and adolescents have mental problems that undermine
      their normal development and functioning. It is estimated that about 10% of
      children and adolescents suffer from mental disorders at a sufficiently severe
      level to cause some degree of damage and require treatment. AIM: The aim of this
      paper is to determine whether there have been changes in the diagnostic
      categories in developmental psychiatry in children and adolescents treated at the
      Department for Children and Adolescent Psychiatry for the last fifteen years.
      SUBJECTS AND METHODS: The survey includes 844 patients treated at the Department
      for Child and Adolescent Psychiatry of University Clinical Center of the Republic
      of Srpska in the period from April 2002 to September 2017, involving only
      children and adolescents who were hospitalized for the first time. The sample
      consisted of 453 female subjects (54, 67%) and 391 male subjects (46, 33%).
      Subjects were divided into three groups: group 1 - hospitalization in the period
      from 2002 to 2007; group 2 - hospitalization in the period from 2008 to 2012;
      group 3 - hospitalization in the period from 2013 to September 2017. RESULTS:
      Female subjects accounted for more than half of the subjects within each group,
      with a mild increase in the number of patients in the last 4 years. In the
      overall sample, adolescents, aged 13 to 18 (51.66%) were the most frequent, with
      the lowest number of subjects under 6 years of age (3.91%). In the overall
      sample, the most frequent are: psychotic disorders in 18.60% of subjects;
      behavioral disorders and emotions in 17, 42% of subjects; suicide attempt, in
      14.34% of subjects. By comparing data by groups, there has been a decline in
      psychotic disorders, and since 2008, adapting disorders and behavioral and
      emotional disorders have been most frequently diagnosed. There is an increase in
      the number of respondents who come from incomplete families in the last few
      years. About one-third of the sample (33.89%) were exposed to one or more types
      of abuse. 43.13% of children and adolescents with poor socio-economic status.
      Comorbid diseases are present in 5.92% of children and adolescents. In 26.18% of
      the sample, psychiatric disorders are present in the family history. The abuse of
      psychoactive substances was observed in 2.61% of adolescents, and this number has
      been increasing for the last five years. Family dysfunction is present in 57.35%
      of children and adolescents. CONCLUSION: In our study, there was an increase in
      the number of children and adolescents with behavioral disorders and adjustment
      disorders, as well as an increase in family dysfunctionality and psychoactive
      substances abuse in adolescents.

PMID- 30235173
TI  - Perceptions on Support, Challenges and Needs among Parents of Children with
      Autism: the Serbian Experience.
AB  - BACKGROUND: Autism spectrum disorders (ASD) significantly impact lives of
      affected individuals and their families. They confront daunting challenges and
      multiple demands in their daily life, when compared to parents of children with
      other disabilities or parents of typically developing children. SUBJECTS AND
      METHODS: Participants completed The Caregiver Needs Survey, the survey intended
      for parents or primary caregivers of children with a diagnosis of ASD. During the
      study, 231 parents were interviewed; 167 mothers and 64 fathers. Parents were
      recruited from the patient database comprised of families from the two largest
      cities in Serbia. All of them were contacted before the study, either via phone
      or at the child's regular check-in visit. RESULTS: Over 90 percent of the parents
      reported that additional support at schools, home, and improved relationships
      with service providers are necessary and important. The most important challenges
      related to care were child's communication difficulties, social interaction
      difficulties, and problems with daily living skills. The significant predictors
      of lower overall satisfaction were parent's higher education, having a first
      concern related to problems of the child's interaction with others or playing
      alone, and parent frustration with accessing services in the past 12 months.
      Greater overall satisfaction, on the other hand, was related to having an in
      school tutor training or assistance in managing child's needs or implementing
      treatments, and having primary care doctor or pediatrician as a source of
      information on autism. CONCLUSIONS: Future efforts to develop ASD-related
      policies and services should also take the following into consideration: the low
      level of awareness among caregivers and health care providers about the early
      signs of autism; disparities in access to services; educational problems and
      significant levels of dissatisfaction with the overall care and stigma.

PMID- 30235174
TI  - Relationship between Early Psychotraumatisation with the Onset and the Course of
      Psychotic Disorders.
AB  - Connections between specific types of altered brain functioning and some mental
      disorders are still not fully clarified. However, there is a large number of
      evidence that indicates mental disorders are results of complex interactions of
      biological and environmental factors. When it comes to environmental factors, the
      main focus in the scientific literature has been particularly focused on early
      psychotraumatisation. Early psychotraumatisation is a multi-layered construct
      that essentially involves sexual, emotional and psychical neglect in childhood
      and emotional and psychical negligence, with about one-fourth of children
      experience a traumatic event before the age of 18. Although most children are
      resilient after traumatic exposure, some develop significant and potentially long
      lasting psychiatric disorders. In addition, the high prevalence of trauma and
      neglect has been found in all types of psychiatric disorders. While early
      psychotraumatisation in patients with psychotic disorders was recently diminished
      or denied altogether, there is now strong evidence that the prevalence of
      childhood adversities in this population is exceptionally high. Regarding this,
      there is an increasing number of sophisticated studies that point out the fact
      that early psychotraumatisation has an important impact on development and
      clinical course of psychosis in adults. It seems that this relation is causal,
      especially when considering severity, frequency, and number of traumatic events.
      In addition, psychotic patients who experience psychotraumatisation at an earlier
      age along with their first psychotic episode are known to be hospitalized more
      often with their psychotic episodes lasting longer; further, they commit suicide
      more often and have more dissociative symptoms. These patients' is poorer such as
      their quality of life in comparison with patients without the experience of early
      psychotraumatisation. Moreover, this type of traumatic experience is very often
      an important determinant of phenomenology of psychotic disorder.

PMID- 30235175
TI  - Addictions without Drugs: Contemporary Addictions or Way of Life?
AB  - In the five thousand years of recorded history there is written evidence of
      various types of addiction. In recent decades scientists focus their attention on
      addictions without the immediate introduction of psychoactive substances into the
      organism or the so-called "addictions without drugs". Studies have revealed a
      number of similarities between drug addictions and addictions without drugs that
      also carry biological, psychological and social consequences in the form of
      addictive activity carvings, adrenaline alarm, dopamine and serotonin secretion,
      tolerance and abstinence syndrome same as classical forms of addiction. Although
      the physiological effect of addiction without drugs on the brain and nervous
      system is not yet sufficiently explored, scientists have found equivalent effects
      on addicts suffering from one or the other type of addiction. These addicts are
      almost generally dysfunctional persons who become prisoners of their own
      passions, and the consequences are numerous technological advantages offered by
      modern times and in some respects a punishment due to the civilization for
      forgetting the man himself. Considering that most people, so and many
      psychiatrist, often accept these addictions as a lifestyle and without any delay
      and awareness of the potential dangers they may pose, we can with certainty say
      that the so-called "addictions without drugs" are the scourge of the 21st
      century. With pathological gambling, which is as old as human civilization, in
      recent decades we meet the growing problems of internet addiction, gambling
      games, which are classified for the first time at DSM V in addictive disorder,
      uncontrolled shopping, food cravings, addiction to sex, weight loss, sports, work
      and many more, which are mostly true addictions, and not only the way of life.
      The aim of this paper is to point to the growing problem of addiction without
      drugs, which is becoming an increasing problem within our community.

PMID- 30235176
TI  - Training the recognition of emotions based on bibliotherapy techniques.
AB  - The deficit of mentalisation skills is a well-known phenomenon in schizophrenia.
      In our study, patients with schizophrenia underwent an 8-session training. The
      procedure was based on bibliotherapy, and we associated each basic emotion
      identified by Ekman with a short story that gave a striking description of that
      emotion. After we read the stories together, the participants were given a
      collection of face portrait photos and they were asked to pick the one that
      illustrated the emotional state of the characters. They were also asked to recall
      a personal memory when they felt the same way. We used the 'Reading the Mind in
      the Eyes' (RMET) test to assess the efficiency of our method. The one-sample t
      test we performed to compare the pre- and post-training values detected a
      significant difference (p=0.000608<0.05). The control group of patients with
      schizophrenia who did not undergo the training presented no significant
      difference between the two RMET tests performed 2 weeks apart (p=0.467). However,
      the two-sample t-test performed on the individual changes in RMET results in the
      study and control groups did detect a significant difference (p=0.000786<0.005).
      Our results suggest that the mentalisation deficit of people suffering from
      schizophrenia can be decreased, therefore their communicative and adaptive skills
      can be developed or at least the deterioration of these skills can be slowed
      down.

PMID- 30235177
TI  - Trauma and Anxiety Disorders throughout lifespan: Fear and anxiety from normality
      to disorder.
AB  - Anxiety disorders are among the most common mental disorders. Anxiety disorders
      and neurotic fear cause significant disruption of the psychosocial functioning of
      the individual. In generalized anxiety disorder, neurotic fear appears in the
      form of fears, expectations, tension, with nothing specifically uncomprehendingly
      crying anticipation, worry, poor concentration, psychic and physical fatigue,
      irritability, restlessness, insomnia, sense of near accident etc. Traumatic
      events in the life of the individual are often referred to as potential relevant
      factors in the occurrence of psychological disorders. Exposure to long-lasting
      traumatic experiences in childhood leads to the prolongation and fixation of the
      emotional state of fear and sadness and the emphasized use of certain defense
      mechanisms that contribute to the structuring of specific clinical images of
      anxiety states.

PMID- 30235179
TI  - Highlights in chronic lymphocytic leukemia from the 2018 American Society of
      Clinical Oncology annual meeting.

PMID- 30235180
TI  - Highlights in chronic lymphocytic leukemia from the 2018 American Society of
      Clinical Oncology Annual Meeting: commentary.

PMID- 30235178
TI  - Marital Status and Survival of Patients with Chondrosarcoma: A Population-Based
      Analysis.
AB  - BACKGROUND Previous studies have shown that differences in marital status
      contribute to different prognoses for certain cancers, but the relationship
      between marital status and the prognosis of chondrosarcoma has not been reported
      previously. MATERIAL AND METHODS In this study, we selected 4502 eligible cases
      through the Surveillance, Epidemiology, and End Results (SEER) database from 1977
      to 2014 to analyze the impact of marital status on chondrosarcoma cancer-specific
      survival (CSS) by Kaplan-Meier method and Cox regression model. RESULTS The sex,
      age, histotype, pathological grade, tumor location, tumor size, SEER stage,
      socioeconomic status, marital status, and treatment were identified as
      independent prognostic factors for chondrosarcoma CSS. Widowed patients presented
      the worst CSS compared with their married, divorced, and single counterparts
      (P<0.001). Subgroup analyses showed widowed patients also had a significantly
      higher risk of cancer-specific mortality compared with married patients in
      localized stage (HR: 1.971, 95% CI: 1.298-2.994, P=0.001), regional stage (HR:
      1.535, 95% CI: 1.094-2.154, P=0.013), low pathological grade (HR: 1.866, 95% CI:
      1.332-2.613, P<0.001), and high pathological grade (HR: 1.662, 95% CI: 1.139
      2.426, P=0.008). CONCLUSIONS Marital status was first identified as an
      independent prognostic factor for chondrosarcoma CSS, and widowhood was always
      associated with a high risk of cancer-specific mortality. It is necessary to
      provide timely psychological treatment for widowed patients in clinical practice,
      which can improve the survival of chondrosarcoma patients.

PMID- 30235181
TI  - Notes from the Field: Responding to an Outbreak of Monkeypox Using the One Health
      Approach - Nigeria, 2017-2018.

PMID- 30235183
TI  - QuickStats: Percentage* of Residential Care Community? Residents with a Fall,S by
      Census Region - United States, 2016 .

PMID- 30235182
TI  - Multidrug-Resistant Campylobacter jejuni Outbreak Linked to Puppy Exposure -
      United States, 2016-2018.
AB  - Campylobacter causes an estimated 1.3 million diarrheal illnesses in the United
      States annually (1). In August 2017, the Florida Department of Health notified
      CDC of six Campylobacter jejuni infections linked to company A, a national pet
      store chain based in Ohio. CDC examined whole-genome sequencing (WGS) data and
      identified six isolates from company A puppies in Florida that were highly
      related to an isolate from a company A customer in Ohio. This information
      prompted a multistate investigation by local and state health and agriculture
      departments and CDC to identify the outbreak source and prevent additional
      illness. Health officials from six states visited pet stores to collect puppy
      fecal samples, antibiotic records, and traceback information. Nationally, 118
      persons, including 29 pet store employees, in 18 states were identified with
      illness onset during January 5, 2016-February 4, 2018. In total, six pet store
      companies were linked to the outbreak. Outbreak isolates were resistant by
      antibiotic susceptibility testing to all antibiotics commonly used to treat
      Campylobacter infections, including macrolides and quinolones. Store record
      reviews revealed that among 149 investigated puppies, 142 (95%) received one or
      more courses of antibiotics, raising concern that antibiotic use might have led
      to development of resistance. Public health authorities issued infection
      prevention recommendations to affected pet stores and recommendations for testing
      puppies to veterinarians. This outbreak demonstrates that puppies can be a source
      of multidrug-resistant Campylobacter infections in humans, warranting a closer
      look at antimicrobial use in the commercial dog industry.

PMID- 30235184
TI  - Age-Associated Trends in Diagnosis and Prevalence of Infection with HIV Among Men
      Who Have Sex with Men - United States, 2008-2016.
AB  - In 2016, two thirds of diagnosed human immunodeficiency virus (HIV) infections in
      the United States were attributed to male-to-male sexual contact (1). The risk
      for sexual acquisition and transmission of HIV changes through the lifespan (2);
      to better guide prevention efforts for gay, bisexual, and other men who have sex
      with men (MSM*), CDC analyzed National HIV Surveillance System? (NHSS) data for
      MSM aged >=13 years by age group (13-29, 30-49, and >=50 years) in 50 states and
      the District of Columbia (DC). During 2008-2016, the annual number of diagnoses
      of HIV infection increased 3% per year among MSM aged 13-29 years, decreased 4%
      per year among those aged 30-49 years and was stable for MSM aged >=50 years. The
      number of HIV diagnoses among MSM aged 13-29 years was four times that of MSM
      aged >=50 years. During 2008-2015, the number of MSM aged >=50 years living with
      diagnosed HIV infection (prevalence of HIV infection) increased an average of 11%
      per year and at year-end 2015 was three times that of MSM aged 13-29 years.
      Racial/ethnic disparities in HIV infection persisted, particularly among younger
      black/African American MSM who accounted for 49% of all diagnoses among MSM aged
      13-29 years during 2008-2016. To avert the most infections and improve health
      outcomes (3), sexually active MSM at risk for HIV infection should be tested at
      least once a year, and, if positive, linked to and retained in HIV medical care
      to achieve viral suppression (4). Those testing negative should be provided HIV
      prevention services, including preexposure prophylaxis (PrEP) (5).

PMID- 30235186
TI  - Responding to a new wave of high potency synthetic cannabinoids.

PMID- 30235185
TI  - CDC Grand Rounds: Promoting Well-Being and Independence in Older Adults.
AB  - Healthy aging is not merely the absence of disease or disability, but requires
      physical and mental health and ongoing social engagement (1). As the average U.S.
      life expectancy increases, recognition that public health can play a vital role
      in promoting healthy, successful aging even in the face of increased prevalence
      of chronic diseases, including types of dementia, among older adults (i.e., aged
      >=65 years) has grown. Furthermore, actively engaging adults in prevention and
      wellness along with involving their caregivers (i.e., the family and friends of
      older adults who provide them with unpaid and informal support and services) can
      serve to prevent or delay the onset of physical disabilities and cognitive
      decline. Adults often are reluctant to discuss their concerns about worsening
      memory with their health care providers although such discussions can lead to
      earlier diagnosis and better care, planning, and support. As advances in public
      health and health care have helped increase life expectancy, public health
      professionals and health care providers have the opportunity to improve the
      quality of life for older adults and their caregivers and reduce the burdens
      associated with aging.

PMID- 30235188
TI  - An ethical dilemma: informed consent, balancing patient dignity and medical
      student participation in sensitive examinations.

PMID- 30235187
TI  - Weight and fitness changes across generations: better evidence can help
      prioritise better public health interventions.

PMID- 30235189
TI  - Intergenerational changes in adolescents' physical fitness and weight in New
      Zealand.
AB  - AIMS: This research examines fitness and body weight in two cohorts of
      adolescents, to determine continuity and changes in these measures across two
      generations. METHODS: Height, weight and fitness were measured in a population
      based cohort of 15 year-olds in 1986/7 (Dunedin Study, n=968). The same measures
      were obtained for their 15-16 year-old children between 2007 and 2015 (Next
      Generation Study, n=343). Fitness was defined as maximal aerobic capacity
      (V'O2max). Height and weight were measured in all participants and fitness was
      adjusted for weight (V'O2max/kg). RESULTS: The Next Generation participants were,
      on average, heavier than the Dunedin Study participants had been, and had higher
      body mass index values (kg/m2). Unadjusted V'O2max values for boys did not differ
      between generations, but were lower in Next Generation girls compared to Dunedin
      Study girls. For both sexes, the Next Generation participants had lower weight
      adjusted V'O2max values than the Dunedin Study participants. Compared to their
      parents, weight-adjusted V'O2max values were approximately 25% lower in girls and
      15% lower in boys. CONCLUSIONS: Overall adolescents today appear to be less fit
      and heavier than their parents were at the same age. The decline in fitness over
      a generation is particularly evident in adolescent girls, although boys also have
      lower levels of fitness once body weight has been taken into account.

PMID- 30235190
TI  - Medical students, sensitive examinations and patient consent: a qualitative
      review.
AB  - AIM: We set out to explore the question, what ethical challenges do medical
      students identify when asked to perform or observe a sensitive examination, given
      a historical background relevant to this context. METHOD: Thematic analysis of 21
      Ethics Reports from 9 female and 12 male students. RESULTS: Overall 14 students
      undertook a sensitive examination without the patient's consent; three did not
      carry out a sensitive examination because of a lack of consent; and two students
      (or their senior colleagues) gained the patient's written consent for the student
      to undertake the examination. One patient refused the student's request for
      consent to perform a digital rectal examination; and in the final case, verbal
      consent was given by the patient for the student to observe a bimanual
      examination only. Three interrelated core themes arose from thematic analysis of
      the research question: systemic constraints on getting consent; internal
      conflicts of interest; and, power and hierarchy. CONCLUSIONS: A number of senior
      medical students at our institution disclosed observing or performing sensitive
      examinations on patients without the patients' knowledge or consent.

PMID- 30235191
TI  - Distinctive features of polycythaemia vera in New Zealand Polynesians.
AB  - AIM: The aim of this study was to examine a potential ethnic disparity in the
      phenotype of polycythaemia vera (PV) between New Zealand European and Polynesian
      patients. METHOD: A retrospective review of medical records was conducted at
      Middlemore Hospital to identify adult patients with PV diagnosed between 1987 and
      2007. Data extracted included diagnostic criteria, ethnicity, age, complications
      and survival. RESULTS: Eighty-eight adult patients with PV were identified during
      1987-2007, 49 (55.7%) were Europeans and 36 (40.9%) Polynesians. The most
      striking finding was that Polynesian patients presented almost 14 years younger
      than Europeans (mean age of 54 years versus [vs] 68, respectively; P<.001). The
      white cell and platelet counts were higher in Polynesians compared with Europeans
      (mean white cell count of 22x109/L vs 13x109/L; mean platelet count of 648x109/L
      vs 512x109/L, respectively; P<.05 for both). The rate of JAK2 V617F mutation in
      Polynesians was 96%, equivalent to other large cohorts of European patients. The
      rates of long-term complications were comparable between Polynesians and
      Europeans, but the predicted impact on life expectancy was more severe for
      Polynesians. CONCLUSION: New Zealand Polynesian patients present with a
      distinctive PV phenotype. Their younger age at presentation suggests a different
      risk factor profile or a higher genetic susceptibility. We hope our observations
      initiate larger epidemiological and genetic studies to help elucidate the cause.

PMID- 30235192
TI  - Comparing initial and follow-up responders to a New Zealand patient experience
      survey.
AB  - AIM: This study investigates non-response bias in an inpatient experience survey
      with a low response rate by comparing sociodemographic characteristics and
      response behaviours of initial responders with responders to follow-up, and
      further explores the factors contributing to non-response. Prior research
      suggests non-response may be endogenously related to patient characteristics.
      METHOD: We re-contacted a convenience sample of non-responders to a nationally
      representative, cross-sectional inpatient survey conducted in New Zealand.
      Participants were given a subset of six items drawn from the initial survey and
      the opportunity to disclose reasons for non-response. Responders to follow-up
      (n=163) were subsequently compared with responders to the initial survey (n=910)
      using chi-squared tests of association and logistic regression to assess
      differences in sociodemographic variables and substantive responses. RESULTS: We
      find no significant differences in the responses given by initial and follow-up
      responders. The most common reasons for non-response were "can't remember" (33%),
      not receiving the survey (25%) or being too busy at the time (25%). CONCLUSION:
      Responders to follow-up have similar experiences of inpatient care in New Zealand
      to initial responders. Further study is needed to strengthen inferences regarding
      hard-to-reach patients.

PMID- 30235193
TI  - Who operated on me? What patients understand about surgical trainees.
AB  - AIMS: To evaluate whether information delivered to patients about the level of
      training of the person operating on them is understandable and meaningful. To
      establish whether post-operative patients can identify when a doctor, undergoing
      training in surgery, has performed their surgery. To identify terms that are
      clear to patients, which can be used to improve understanding. METHOD: A 15
      question survey was developed to evaluate the expectations, understanding and
      knowledge post-operative patients had about their recent surgery. Patients were
      questioned about the level of training of their surgeon, the current designations
      used and their knowledge about surgical training. RESULTS: Over a one-month
      period, 161 patients were requested to fill in surveys. Sixty-one percent of
      patients agreed that it is very important to know the level of training of their
      surgeon, but only 39% of patients could correctly identify this. Of the 62
      patients who thought that a consultant had performed their procedure, 40% were
      correct. The terms we use to denote level of training are confusing to the
      majority of patients. CONCLUSION: The majority of patients are unable to
      recognise the level of training of the person who operated on them. There is a
      common public misconception that the consultant surgeon will be the operator in
      the majority procedures, however in teaching hospitals, a significant number of
      procedures are performed by doctors working under the supervision of the
      consultant surgeon. Many patients are not being adequately educated prior to
      surgery about the level of training of the person doing their procedure.

PMID- 30235194
TI  - Epidemiology of melanoma in situ in New Zealand: 2008-2012.
AB  - AIM: The incidence of melanoma in situ varies throughout the world. It is
      associated with excellent outcomes, however many of those untreated will go on to
      develop invasive melanoma with a worse prognosis. There is no previously
      published data on melanoma in situ (MIS) in New Zealand. Further information is
      needed to enable better understanding of the disease spectrum. METHODS: De
      identified data were obtained from the New Zealand Cancer Registry (NZCR) by way
      of computerised search for MIS diagnosis. A separate search was performed to
      identify all patients with invasive melanoma. World Health Organization standard
      population was used for calculating age standardised rates. RESULTS: There was a
      trend to increasing cases of MIS, but a relative plateauing of invasive melanoma.
      The number of cases for MIS overtook invasive melanoma in 2012. Overall, men had
      a significantly higher incidence compared to women. Incidence rates varied
      markedly between different regions of the country. CONCLUSIONS: This paper
      provides new information about the epidemiology of MIS in New Zealand and its
      relevance to clinical practice. Public education strategies may be beginning to
      show effect with the goal of increasing prevention and earlier detection and
      treatment to enable decrease in melanoma mortality.

PMID- 30235195
TI  - Perioperative ischaemic stroke in patients with atrial fibrillation after
      temporary cessation of anticoagulation for elective surgery.

PMID- 30235198
TI  - "If government can't stop the smokes, no way we can stop selling them": why
      retailers want Government to act.

PMID- 30235196
TI  - Cerebellar dysmetria treated using a wrist band.

PMID- 30235197
TI  - Lack of perspective in health funding research criticised.

PMID- 30235199
TI  - Primum non nocere: first do no harm: reponse to Phillida Bunkle.

PMID- 30235200
TI  - Clarification on maternal alcohol consumption.

PMID- 30235201
TI  - Aging alters the epigenetic asymmetry of HSC division.
AB  - Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to
      maintain homeostasis. With aging, the frequency of polar HSCs decreases. Cell
      polarity in HSCs is controlled by the activity of the small RhoGTPase cell
      division control protein 42 (Cdc42). Here we demonstrate-using a comprehensive
      set of paired daughter cell analyses that include single-cell 3D confocal
      imaging, single-cell transplants, single-cell RNA-seq, and single-cell
      transposase-accessible chromatin sequencing (ATAC-seq)-that the outcome of HSC
      divisions is strongly linked to the polarity status before mitosis, which is in
      turn determined by the level of the activity Cdc42 in stem cells. Aged apolar
      HSCs undergo preferentially self-renewing symmetric divisions, resulting in
      daughter stem cells with reduced regenerative capacity and lymphoid potential,
      while young polar HSCs undergo preferentially asymmetric divisions. Mathematical
      modeling in combination with experimental data implies a mechanistic role of the
      asymmetric sorting of Cdc42 in determining the potential of daughter cells via
      epigenetic mechanisms. Therefore, molecules that control HSC polarity might serve
      as modulators of the mode of stem cell division regulating the potential of
      daughter cells.

PMID- 30235202
TI  - Transition state characteristics during cell differentiation.
AB  - Models describing the process of stem-cell differentiation are plentiful, and may
      offer insights into the underlying mechanisms and experimentally observed
      behaviour. Waddington's epigenetic landscape has been providing a conceptual
      framework for differentiation processes since its inception. It also allows,
      however, for detailed mathematical and quantitative analyses, as the landscape
      can, at least in principle, be related to mathematical models of dynamical
      systems. Here we focus on a set of dynamical systems features that are intimately
      linked to cell differentiation, by considering exemplar dynamical models that
      capture important aspects of stem cell differentiation dynamics. These models
      allow us to map the paths that cells take through gene expression space as they
      move from one fate to another, e.g. from a stem-cell to a more specialized cell
      type. Our analysis highlights the role of the transition state (TS) that
      separates distinct cell fates, and how the nature of the TS changes as the
      underlying landscape changes-change that can be induced by e.g. cellular
      signaling. We demonstrate that models for stem cell differentiation may be
      interpreted in terms of either a static or transitory landscape. For the static
      case the TS represents a particular transcriptional profile that all cells
      approach during differentiation. Alternatively, the TS may refer to the commonly
      observed period of heterogeneity as cells undergo stochastic transitions.

PMID- 30235204
TI  - Minutes to midnight: Turning back the Doomsday Clock through neglected disease
      vaccine diplomacy.

PMID- 30235203
TI  - Pseudomonas aeruginosa displays a dormancy phenotype during long-term survival in
      water.
AB  - Pseudomonas aeruginosa is capable of long-term survival in water, which may serve
      as a reservoir for infection. Although viable cell counts of PAO1 incubated in
      water remain stable throughout 8 weeks, LIVE/DEAD staining indicated a high
      proportion of cells stained with propidium iodide (PI). The proportion of PI
      stained cells increased by 4 weeks, then decreased again by 8 weeks, suggesting
      an adaptive response. This was also evident in an observed shift in cell
      morphology from a rod to a coccoid shape after 8 weeks. Fluorescence-activated
      cell sorting (FACS) was used to recover PI-stained cells, which were plated and
      shown to be viable, indicating that PI-stained cells were membrane-compromised
      but still cultivable. PAO1 mid-log cells in water were labeled with the dsDNA
      binding dye PicoGreen to monitor viability as well as DNA integrity, which
      demonstrated that the population remains viable and transitions towards increased
      dsDNA staining. Metabolic activity was found to decrease significantly in water
      by 4 weeks. The PAO1 outer membrane became less permeable and more resistant to
      polymyxin B damage in water, and the profile of total membrane lipids changed
      over time. Among the ~1400 transcriptional lux fusions, gene expression in water
      revealed that the majority of genes were repressed, but subsets of genes were
      induced at particular time points. In summary, these results indicate that P.
      aeruginosa is dormant in water and this adaptation involves a complex pattern of
      gene regulation and changes to the cell to promote long-term survival and
      antibiotic tolerance. The approach of P. aeruginosa incubated in water may be
      useful to study antibiotic tolerance and the mechanisms of dormancy and survival
      in nutrient limiting conditions.

PMID- 30235206
TI  - Merle phenotypes in dogs - SILV SINE insertions from Mc to Mh.
AB  - It has been recognized that the Merle coat pattern in dogs is not only a visually
      interesting feature, but it also exerts an important biological role, in terms of
      hearing and vision impairments. In 2006, the Merle (M) locus was mapped to the
      SILV gene (aka PMEL) with a SINE element in it, and the inserted retroelement was
      proven causative to the Merle phenotype. Mapping of the M locus was a genetic
      breakthrough and many breeders started implementing SILV SINE testing in their
      breeding programs. Unfortunately, the situation turned out complicated as
      genotypes of Merle tested individuals did not always correspond to expected
      phenotypes, sometimes with undesired health consequences in the offspring. Two
      variants of SILV SINE, allelic to the wild type sequence, have been described so
      far-Mc and M. Here we report a significantly larger portfolio of existing Merle
      alleles (Mc, Mc+, Ma, Ma+, M, Mh) in Merle dogs, which are associated with unique
      coat color features and stratified health impairment risk. The refinement of
      allelic identification was made possible by systematic, detailed observation of
      Merle phenotypes in a cohort of 181 dogs from known Merle breeds, by many
      breeders worldwide, and the use of advanced molecular technology enabling the
      discrimination of individual Merle alleles with significantly higher precision
      than previously available. We also show that mosaicism of Merle alleles is an
      unexpectedly frequent phenomenon, which was identified in 30 out of 181 (16.6%)
      dogs in our study group. Importantly, not only major alleles, but also minor
      Merle alleles can be inherited by the offspring. Thus, mosaic findings cannot be
      neglected and must be reported to the breeder in their whole extent. Most
      importantly, sperm cells seem to be a significant source of germline Merle
      allelic variants which can be passed to the offspring on Mendelian basis and
      explain unusual genotype / phenotype findings in the offspring. In light of
      negative health consequences that may be attributed to certain Merle breeding
      strategies, we strongly advocate implementation of the refined Merle allele
      testing for all dogs of Merle breeds to help the breeders in selection of
      suitable mating partners and production of healthy offspring.

PMID- 30235205
TI  - Coinfections and comorbidities in African health systems: At the interface of
      infectious and noninfectious diseases.
AB  - There is a disease epidemiological transition occurring in Africa, with
      increasing incidence of noninfectious diseases, superimposed on a health system
      historically geared more toward the management of communicable diseases. The
      persistence and sometimes emergence of new pathogens allows for the occurrence of
      coinfections and comorbidities due to both infectious and noninfectious diseases.
      There is therefore a need to rethink and restructure African health systems to
      successfully address this transition. The historical focus of more health
      resources on infectious diseases requires revision. We hypothesise that the
      growing burden of noninfectious diseases may be linked directly and indirectly to
      or further exacerbated by the existence of neglected tropical diseases (NTDs) and
      other infectious diseases within the population. Herein, we discuss the health
      burden of coinfections and comorbidities and the challenges to implementing
      effective and sustainable healthcare in Africa. We also discuss how existing NTD
      and infectious disease intervention programs in Africa can be leveraged for
      noninfectious disease intervention. Furthermore, we explore the potential for new
      technologies-including artificial intelligence and multiplex approaches-for
      diagnosis and management of chronic diseases for improved health provision in
      Africa.

PMID- 30235207
TI  - Maintaining maximal metabolic flux by gene expression control.
AB  - One of the marvels of biology is the phenotypic plasticity of microorganisms. It
      allows them to maintain high growth rates across conditions. Studies suggest that
      cells can express metabolic enzymes at tuned concentrations through adjustment of
      gene expression. The associated transcription factors are often regulated by
      intracellular metabolites. Here we study metabolite-mediated regulation of
      metabolic-gene expression that maximises metabolic fluxes across conditions. We
      developed an adaptive control theory, qORAC (for 'Specific Flux (q) Optimization
      by Robust Adaptive Control'), and illustrate it with several examples of
      metabolic pathways. The key feature of the theory is that it does not require
      knowledge of the regulatory network, only of the metabolic part. We derive that
      maximal metabolic flux can be maintained in the face of varying N environmental
      parameters only if the number of transcription-factor binding metabolites is at
      least equal to N. The controlling circuits appear to require simple biochemical
      kinetics. We conclude that microorganisms likely can achieve maximal rates in
      metabolic pathways, in the face of environmental changes.

PMID- 30235209
TI  - Reinterpretation of the localization of the ATP binding cassette transporter
      ABCG1 in insulin-secreting cells and insights regarding its trafficking and
      function.
AB  - The ABC transporter ABCG1 contributes to the regulation of cholesterol efflux
      from cells and to the distribution of cholesterol within cells. We showed
      previously that ABCG1 deficiency inhibits insulin secretion by pancreatic beta
      cells and, based on its immunolocalization to insulin granules, proposed its
      essential role in forming granule membranes that are enriched in cholesterol.
      While we confirm elsewhere that ABCG1, alongside ABCA1 and oxysterol binding
      protein OSBP, supports insulin granule formation, the aim here is to clarify the
      localization of ABCG1 within insulin-secreting cells and to provide added insight
      regarding ABCG1's trafficking and sites of function. We show that stably
      expressed GFP-tagged ABCG1 closely mimics the distribution of endogenous ABCG1 in
      pancreatic INS1 cells and accumulates in the trans-Golgi network (TGN), endosomal
      recycling compartment (ERC) and on the cell surface but not on insulin granules,
      early or late endosomes. Notably, ABCG1 is short-lived, and proteasomal and
      lysosomal inhibitors both decrease its degradation. Following blockade of protein
      synthesis, GFP-tagged ABCG1 first disappears from the ER and TGN and later from
      the ERC and plasma membrane. In addition to aiding granule formation, our
      findings raise the prospect that ABCG1 may act beyond the TGN to regulate
      activities involving the endocytic pathway, especially as the amount of
      transferrin receptor is increased in ABCG1-deficient cells. Thus, ABCG1 may
      function at multiple intracellular sites and the plasma membrane as a roving
      sensor and modulator of cholesterol distribution, membrane trafficking and
      cholesterol efflux.

PMID- 30235208
TI  - Molecular characterization and phylogenetic analysis of dengue viruses imported
      into Taiwan during 2011-2016.
AB  - A total of 1,596 laboratory-confirmed imported dengue cases were identified in
      Taiwan during 2011-2016. Most of the imported cases arrived from Southeast Asia
      as well as the Indian subcontinent, the Pacific region, Latin America, Australia
      and Africa. Phylogenetic analyses of the complete envelope protein gene sequences
      from 784 imported dengue virus (DENV) isolates were conducted, and the results
      suggest that the DENV-1 genotype I and DENV-2 Cosmopolitan genotype comprise the
      predominant serotype/genotype of DENV strains circulating in Southeast Asia. The
      DENV-1 genotype III, DENV-3 genotype III and DENV-4 genotype I and II strains
      were found to be newly emerging in several Southeast Asian countries. Our results
      also showed that geographical restrictions of DENV-1 genotype I, DENV-1 genotype
      III and DENV-2 Cosmopolitan genotype are becoming blurred, indicating the
      extensive introductions and continuous expansions of DENV strains between nations
      in Southeast Asia. In this study, we present the geographic distribution and
      dynamic transmission of DENV strains circulating in Southeast Asian countries. In
      addition, we demonstrated local dengue epidemics caused by several imported DENV
      strains in Taiwan during 2011-2016.

PMID- 30235210
TI  - Detection and distribution of Sca autotransporter protein antigens in diverse
      isolates of Orientia tsutsugamushi.
AB  - Orientia tsutsugamushi (Ots) frequently causes severe scrub typhus infections in
      the Asia-Pacific region. Korean investigators have demonstrated that Ots encodes
      five different autotransporter domain (ATD) proteins (ScaA-ScaE). ScaA functions
      as an adhesin and confers protective immunity in a lethal mouse model of Ots
      infection. Specific antibodies are detected against ScaA and ScaC in Korean scrub
      typhus patients. However, there is limited data on the distribution of the Sca
      protein genes in diverse isolates of Ots. By BLAST analysis with the conserved
      beta barrel autotransporter domain (ATD) regions of the sca proteins, we
      discovered a sixth gene scaF among 3 of 10 new partial Ots genome sequences
      available at NCBI GenBank (Sido, Karp, AFSC7). We designed two to seven specific
      TaqMan assays to detect the ATD for each of the six sca genes. The TaqMan assays
      among those for each sca gene which gave the greatest sensitivity and linearity
      with DNA log dilutions were then used for screening DNAs from Ots isolates grown
      in L929 mouse cells for sca genes. The sca prevalence survey was performed for
      all six sca genes with 178 DNAs from isolates from 12 countries. The survey
      results were confirmed by conventional PCR with primers from conserved regions of
      the passenger domains (PD) and ATD of the sca proteins. The ATD was highly
      conserved between the DNAs of different genotypes compared to the sca PD but each
      TaqMan assay was sca specific. The percentage positivity for 56 kDa and scaA
      genes in the 178 DNAs using Ha primers was 59.6% and 62.4%, respectively. Our
      scaA conventional ATD PCR assay was positive in 98.3% but scaA was present in all
      178 DNAs (100%) by ATD TaqMan. scaB, scaC, scaD, scaE and scaF were detected in
      33.7%, 97.8%, 93.8%, 97.2% and 43.3% isolates by ATD TaqMan, respectively. The
      ATDs of Ots sca genes are thus sufficiently conserved between different genotypes
      for molecular assay design. Four sca genes are widely distributed among diverse
      Ots isolates from diverse geographical areas. scaB and scaF were detected in
      fewer Ots isolates and absent from some available genome sequences. Whether the
      utility of the ScaA, ScaC, ScaD, and ScaE antigenic passenger protein domains
      exceeds that of the mixed 56 kDa type surface antigens of Ots now used in
      combination diagnostic assays needs to be determined before they can be
      considered as suitable alternative serological antigens for diagnosis of scrub
      typhus.

PMID- 30235211
TI  - Health preparedness plan for dengue detection during the 2020 summer Olympic and
      Paralympic games in Tokyo.
AB  - BACKGROUND: Participants in mass gathering events are at risk of acquiring
      imported and locally endemic infectious diseases. The 2014 dengue outbreak in
      Tokyo gathered attention since it was the first time in 70 years for Japan to
      experience an autochthonous transmission. Preparation for emerging infectious
      threats is essential even in places where these outbreaks have been largely
      unknown. The aim of this study is to identify strategies for early detection and
      prevention of dengue infection during the 2020 summer Olympics and Paralympics in
      Tokyo. METHODOLOGY/PRINCIPAL FINDINGS: We modified and adapted the failure mode
      and effect analysis (FMEA) methodology, generally used in industrial
      manufacturing, to examine the current controls for dengue detection and
      assessment. Information on existing controls were obtained from publicly
      available resources. Our analysis revealed that the national infectious disease
      control system to detect dengue in Japan is robust. However, in the case of large
      assemblies of international visitors for special events when the spread of
      communicable and vector-borne diseases increases, there are three main gaps that
      could be reinforced. First, cyclical training or a certification program on
      tropical disease management is warranted for physicians, especially those working
      in non-infectious disease-designated hospitals or clinics. Second, multi-language
      communication methods need to be strengthened especially in the health and
      hospitality sector. Third, owners of accommodations should consider incorporating
      a formal tropical disease-training program for their staff members and have a
      contingency plan for infectious disease-suspected travelers.
      CONCLUSIONS/SIGNIFICANCE: Our findings may facilitate physicians and public
      health officials where new controls would be beneficial for the 2020 summer
      Olympics and Paralympics. The FMEA framework has the potential to be applied to
      other infectious diseases, not just dengue.

PMID- 30235213
TI  - Morphological description, character conceptualization and the reconstruction of
      ancestral states exemplified by the evolution of arthropod hearts.
AB  - Arthropods are the most species-rich taxon within Metazoa and have gone through
      major evolutionary changes with regard to body organization. Arthropod hearts and
      their associated vascular systems are thus morphologically highly disparate:
      while some arthropods exhibit very powerful hearts and complex vascular systems,
      other arthropods do not possess any kind of vascular system or heart at all. A
      comprehensive study investigating the structure of arthropods hearts has never
      been undertaken. In this study, we therefore investigate the hearts of 34 species
      from all major arthropod groups using various imaging techniques (confocal laser
      scanning microscopy, micro-computed tomography, histology) and describe them by
      addressing different aspects of heart morphology, e.g. the structure of the
      myocard or the composition of ostia. In a next step, we conceptualize 18
      characters related to heart morphology and their respective character states and
      using additional data from the literature-score a matrix for a total of 45
      species from 38 supraspecific taxa. We map the characters onto prevailing
      phylogenetic hypotheses and perform parsimony-based ancestral state
      reconstruction to trace the evolutionary transformations undergone by arthropod
      hearts. An exploration of the character concepts (as explanatory hypotheses)
      reveals ontological peculiarities of character statements that clearly
      distinguish them in terms of ontological status from descriptive statements (i.e.
      descriptions of morphemes). The implications of these findings influence the
      interpretation of ground patterns as explanations. This first phylogenetic
      approach to heart morphology in the arthropod ground pattern reveals numerous new
      putative synapomorphies and leads to a reconsideration of the morphology of
      circulatory systems in early arthropods. Hypotheses on the evolution of hearts in
      (Pan-) Arthropoda are illustrated and discussed.

PMID- 30235212
TI  - Modulation of ACD6 dependent hyperimmunity by natural alleles of an Arabidopsis
      thaliana NLR resistance gene.
AB  - Plants defend themselves against pathogens by activating an array of immune
      responses. Unfortunately, immunity programs may also cause unintended collateral
      damage to the plant itself. The quantitative disease resistance gene ACCELERATED
      CELL DEATH 6 (ACD6) serves to balance growth and pathogen resistance in natural
      populations of Arabidopsis thaliana. An autoimmune allele, ACD6-Est, which
      strongly reduces growth under specific laboratory conditions, is found in over
      10% of wild strains. There is, however, extensive variation in the strength of
      the autoimmune phenotype expressed by strains with an ACD6-Est allele, indicative
      of genetic modifiers. Quantitative genetic analysis suggests that ACD6 activity
      can be modulated in diverse ways, with different strains often carrying different
      large-effect modifiers. One modifier is SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1
      (SNC1), located in a highly polymorphic cluster of nucleotide-binding domain and
      leucine-rich repeat (NLR) immune receptor genes, which are prototypes for
      qualitative disease resistance genes. Allelic variation at SNC1 correlates with
      ACD6-Est activity in multiple accessions, and a common structural variant
      affecting the NL linker sequence can explain differences in SNC1 activity. Taken
      together, we find that an NLR gene can mask the activity of an ACD6 autoimmune
      allele in natural A. thaliana populations, thereby linking different arms of the
      plant immune system.

PMID- 30235214
TI  - Effect of smoking status on neuronal responses to graphic cigarette warning
      labels.
AB  - BACKGROUND: Smoking is responsible for a large proportion of cancer, respiratory
      and cardiovascular deaths. Nevertheless the health risks of smoking are still
      underestimated in many smokers. The present study aimed to examine
      neurobiological responses to graphical warnings on cigarette packings in non
      smokers and patients with tobacco dependence. METHODS: Twenty non-smokers and
      twenty-four patients with tobacco dependence participated in a functional MRI
      study during that pictures of different categories were presented ((a) EU-warning
      pictures, (b) text-only warnings, (c) neutral pictures with short information).
      Patients contributed twice in the experiment (after 10 hours nicotine withdrawal
      / about 5 minutes after nicotine consumption). RESULTS: Smokers during withdrawal
      demonstrated increased neuronal responses predominantly in subcortical, temporal
      and frontal brain regions that are associated with emotional and cognitive
      processes during the presentation of graphical warnings compared to neutral
      pictures. In smokers after smoking and non-smokers, the differences between
      graphical warnings and neutral pictures were increased compared to smokers during
      withdrawal. The comparison of the graphical warnings with text-only labels
      demonstrated the importance of affective brain regions especially in smokers
      after smoking and in non-smokers. During withdrawal, the neural responses
      associated with graphical warnings and text-only labels differed only marginally.
      DISCUSSION AND CONCLUSION: The results suggest that emotional and cognitive
      reactions to graphical warnings are predominantly seen in smokers after smoking
      and in non-smokers. The impact of these pictures during withdrawal seems to be
      less pronounced; in this case, more unspecific processes seem to be important,
      including the projection of sensory signals to the cerebral cortex.

PMID- 30235215
TI  - Improving the SIENA performance using BEaST brain extraction.
AB  - We present an improved image analysis pipeline to detect the percent brain volume
      change (PBVC) using SIENA (Structural Image Evaluation, using Normalization, of
      Atrophy) in populations with Alzheimer's dementia. Our proposed approach uses the
      improved brain extraction mask from BEaST (Brain Extraction based on nonlocal
      Segmentation Technique) instead of the conventional BET (Brain Extraction Tool)
      for SIENA. We compared four varying options of BET as well as BEaST and applied
      these five methods to analyze scan-rescan MRIs in ADNI from 332 subjects,
      longitudinal ADNI MRIs from the same 332 subjects, their repeat scans over time,
      and OASIS longitudinal MRIs from 123 subjects. The results showed that BEaST
      brain masks were consistent in scan-rescan reproducibility. The cross-sectional
      scan-rescan error in the absolute percent brain volume difference measured by
      SIENA was smallest (p<=0.0187) with the proposed BEaST-SIENA. We evaluated the
      statistical power in terms of effect size, and the best performance was achieved
      with BEaST-SIENA (1.2789 for ADNI and 1.095 for OASIS). The absolute difference
      in PBVC between scan-dataset (volume change from baseline to year-1) and rescan
      dataset (volume change from baseline repeat scan to year-1 repeat scan) was also
      the smallest with BEaST-SIENA compared to the BET-based SIENA and had the highest
      correlation when compared to the BET-based SIENA variants. In conclusion, our
      study shows that BEaST was robust in terms of reproducibility and consistency and
      that SIENA's reproducibility and statistical power are improved in multiple
      datasets when used in combination with BEaST.

PMID- 30235216
TI  - Epidemiological and economic burden of potentially HPV-related cancers in France.
AB  - Human papillomaviruses (HPV) infection is now known to be responsible for almost
      all cervical cancers, and for a substantial fraction of Head and Neck cancers
      (HNCs). However, comprehensive epidemiological and economic data is lacking in
      France, especially for rarer potentially HPV-related cancers, which include anal,
      vulvar and vaginal cancers. Using the national comprehensive database of French
      public and private hospital information (PMSI), we assessed prevalence and
      incidence of patients with in-hospital diagnosis for potentially HPV-related
      cancers in 2013, and estimated costs related to their management over a 3-year
      period after diagnosis in France. Concerning female genital cancers, 7,597, 1,491
      and 748 women were hospitalized for cervical, vulvar and vaginal cancer in 2013,
      respectively, with 3,120, 522 and 323 of them being new cases. A total of 4,153
      patients were hospitalized for anal cancer in 2013, including 1,661 new cases.
      For HNCs, 8,794 and 14,730 patients were hospitalized for oral and oropharyngeal
      cancer in 2013, respectively; 3,619 and 6,808 were new cases. Within the 3 years
      after cancer diagnosis, the average cost of hospital care per patient varied from
      ?28 K for anal cancer to ?41 K for oral cancer. Most expenditures were related to
      hospital care, before outpatient care and disability allowance; they were
      concentrated in the first year of care. The total economic burden associated with
      HPV-potentially related cancers was about ?511 M for the French National Health
      Insurance over a 3 years period (2011 to 2013), ranging from ?8 M for vaginal
      cancer to ?222 M for oropharyngeal cancer. This study reported the most up-to
      date epidemiological and economic data on potentially HPV-related cancers in
      France. These results may be used to evaluate the potential impact of new
      preventive strategies, namely the generalized organized screening of cervical
      cancer and the nine-valent HPV vaccine, indicated in the prevention of cervical,
      vaginal, vulvar and anal cancers.

PMID- 30235217
TI  - Economic correlates of footbinding: Implications for the importance of Chinese
      daughters' labor.
AB  - BACKGROUND: It is a wide-spread assumption about footbinding that footbound girls
      and women were more of an economic burden on their families than those never
      bound. It is often presumed that government policies and missionary campaigns
      ended footbinding. METHODS/ OBJECTIVES: We use regression and log-likelihood
      tests, with bootstrapping for confirmation, to analyze which of a series of
      ethnographically and historically hypothesized variables significantly correlate
      with footbinding. We also consider an indirect measure of government
      prohibitions. We analyze two large datasets based on oral surveys with elderly
      women of the last footbound generations from 12 inland Chinese provinces.
      CONCLUSIONS: Handicraft production, particularly commercial handicraft
      production, correlates with whether Chinese girls were subjected to footbinding
      before 1950. Girlhood knowledge of government prohibitions against footbinding,
      an indirect measure of awareness by the adults who decided whether to bind a
      girl's feet, did not correlate with whether women were ever footbound. Spinning
      cotton thread for commercial purposes (sale, wage, direct exchange) correlated
      with greater daily production, with great county-level variation in quantity
      produced. Moreover, Chinese commercial spinners labored more years before
      marriage than domestic spinners. IMPLICATIONS: Chinese daughters-whether
      footbound or not-made important economic contributions to rural households, thus
      suggesting a need to revise our understanding of China's gender and economic
      history. Further implications of our results are that research is warranted on
      the assumed efficacy of government prohibitions-in both rural and urban areas-and
      on the presumption that footbinding among elite Chinese women was unrelated to
      economic concerns, including handicraft production. The demonstrated economic
      correlates of footbinding in inland, rural China also suggest a need to
      reevaluate whether contemporary customs controlling and cloistering girls and
      women, such as female genital cutting in Africa and the threat of honor killings
      of girls and women in South Asia, might have economic correlates.

PMID- 30235218
TI  - Searching for visual features that explain response variance of face neurons in
      inferior temporal cortex.
AB  - Despite a large body of research on response properties of neurons in the
      inferior temporal (IT) cortex, studies to date have not yet produced quantitative
      feature descriptions that can predict responses to arbitrary objects. This
      deficit in the research prevents a thorough understanding of object
      representation in the IT cortex. Here we propose a fragment-based approach for
      finding quantitative feature descriptions of face neurons in the IT cortex. The
      development of the proposed method was driven by the assumption that it is
      possible to recover features from a set of natural image fragments if the set is
      sufficiently large. To find the feature from the set, we compared object
      responses predicted from each fragment and responses of neurons to these objects,
      and search for the fragment that revealed the highest correlation with neural
      object responses. Prediction of object responses of each fragment was made by
      normalizing Euclidian distance between the fragment and each object to 0 to 1
      such that the smaller distance gives the higher value. The distance was
      calculated at the space where images were transformed to a local orientation
      space by a Gabor filter and a local max operation. The method allowed us to find
      features with a correlation coefficient between predicted and neural responses of
      0.68 on average (number of object stimuli, 104) from among 560,000 feature
      candidates, reliably explaining differential responses among faces as well as a
      general preference for faces over to non-face objects. Furthermore, predicted
      responses of the resulting features to novel object images were significantly
      correlated with neural responses to these images. Identification of features
      comprising specific, moderately complex combinations of local orientations and
      colors enabled us to predict responses to upright and inverted faces, which
      provided a possible mechanism of face inversion effects. (292/300).

PMID- 30235219
TI  - RNA-seq analysis of bovine adipose tissue in heifers fed diets differing in
      energy and protein content.
AB  - Adipose tissue is no longer considered a mere energy reserve, but a metabolically
      and hormonally active organ strongly associated with the regulation of whole-body
      metabolism. Knowledge of adipose metabolic regulatory function is of great
      importance in cattle management, as it affects the efficiency and manner with
      which an animal converts feedstuff to milk, meat and fat. However, the molecular
      mechanisms regulating metabolism in bovine adipose tissue are still not fully
      elucidated. The emergence of next-generation sequencing technologies has
      facilitated the analysis of metabolic function and regulation at the global gene
      expression level. The aim of this study was to investigate the effect of diets
      differing in protein and energy density level on gene expression in adipose
      tissue of growing replacement dairy heifers using next-generation RNA sequencing
      (RNAseq). Norwegian Red heifers were fed either a high- or low-protein
      concentrate (HP/LP) and a high- or low-energy roughage (HE/LE) diet from 3 months
      of age until confirmed pregnancy to give four treatments (viz, HPHE, HPLE, LPHE,
      LPLE) with different growth profiles. Subcutaneous adipose tissue sampled at 12
      months of age was analyzed for gene expression differences using RNAseq. The
      largest difference in gene expression was found between LPHE and LPLE heifers,
      for which 1092 genes were significantly differentially expressed, representing an
      up-regulation of mitochondrial function, lipid, carbohydrate and amino acid
      metabolism as well as changes in the antioxidant system in adipose tissue of LPHE
      heifers. Differences between HPHE and HPLE heifers were much smaller, and
      dominated by genes representing NAD biosynthesis, as was the significantly
      differentially expressed genes (DEG) common to both HE-LE contrasts. Differences
      between HP and LP groups within each energy treatment were minimal. This study
      emphasizes the importance of transcriptional regulation of adipose tissue energy
      metabolism, and identifies candidate genes for further studies on early-stage
      obesity and glucose load in dairy cattle.

PMID- 30235221
TI  - Successful adherence and retention to daily monitoring of physical activity:
      Lessons learned.
AB  - Research utilizing repeated-measures such as daily assessments with self-report
      and/or objective measures [e.g., physical activity (PA) monitors] are important
      in understanding health behaviors and informing practice and policy. However,
      studies that utilize daily assessment often encounter issues with attrition and
      non-compliance. The current research yielded high levels of retention and
      adherence with both self-report and objective daily measures. The purpose of this
      paper is to highlight and discuss strategies utilized in maximizing retention,
      minimizing missing data, and some lessons learned from the research experience.
      Fifty community participants took part in a 4-week study utilizing both daily
      self-report questionnaires and daily use of PA monitors (Fitbit OneTM). This
      study focused on typical daily PA and was not an intervention study (e.g.,
      participants were not randomized nor asked to change their PA behavior).
      Participants completed the study in two waves (wave 1 n = 10, wave 2 n = 40). The
      research team utilized several retention strategies including automating the data
      collection process, a prorated incentive structure, having a dedicated and
      responsive study staff, and utilizing the 2-wave process to optimize data
      collection during the 2nd wave. The study had 100% retention and generally
      positive anonymous feedback post-study. Overall, participants completed the vast
      majority of daily surveys (97%) and wore their Fitbits (for at least part of the
      day) on almost all days (99.57%) of the study, although there were individual
      differences. The strategies discussed and lessons learned may be useful to other
      researchers using daily measurements for whom adherence and retention are
      important issues. Future research employing these strategies in different
      populations, with different measurements, and for longer durations is warranted
      to determine generalizability.

PMID- 30235222
TI  - Exploring the roots of antagony in the safe male circumcision partnership in
      Botswana.
AB  - BACKGROUND: Partnerships in global health and development governance have been
      firmly established as a tool to achieve effective outcomes. Botswana implements
      Safe Male Circumcision (SMC) for HIV prevention through a North-South partnership
      comprising the local Ministry of Health, US Centers for Disease Control and
      Prevention (funded by PEPFAR) and Africa Comprehensive HIV/AIDS Partnership
      (funded by the Bill and Melinda Gates Foundation). The SMC partnership
      experienced significant antagony and the aim of this paper is to illuminate the
      actions and processes in the SMC program that contributed to that antagony.
      METHODS: Methods used to gather data include observation of the partners'
      planning and strategic meeting in 2012, in-depth interviews with lead officers at
      national level, focus group discussions with district officers and implementers,
      younger male officers and old community members as recipients of the service.
      RESULTS: The findings reveal that the partnership experienced antagony during
      operational processes and as the ultimate outcome. Target setting, financial
      power of the North, superficial ownership given to the South, ignoring local
      traditional realities results in antagony. Three roots of antagony have been
      identified: 1. therapeutic domination-medical expertise given with arrogance;
      2.iatrogenic violence-good intentions that cause unintended harm; 3. the Trojan
      horse-Reckless acceptance of the gift as well as deceptive power positioned under
      the pretext of benevolence. CONCLUSION: The three roots of antagony; therapeutic
      domination, iatrogenic violence and the Trojan horse, constitute attitudes,
      hidden intentions and unintended consequences that influence program
      implementation and cause harm at different levels. Examples of therapeutic
      domination and the Trojan horse have highlighted the need for vigilance at the
      stage of establishing a partnership, to prevent more powerful partners from
      developing and applying hidden agendas and to strengthen accountability from the
      local partner. Iatrogenic violence has highlighted the need for partnership
      interventions to prevent good partner intentions accidentally producing bad
      outcomes.

PMID- 30235220
TI  - Proteomic analysis of rat serum revealed the effects of chronic sleep deprivation
      on metabolic, cardiovascular and nervous system.
AB  - Sleep is an essential and fundamental physiological process that plays crucial
      roles in the balance of psychological and physical health. Sleep disorder may
      lead to adverse health outcomes. The effects of sleep deprivation were
      extensively studied, but its mechanism is still not fully understood. The present
      study aimed to identify the alterations of serum proteins associated with chronic
      sleep deprivation, and to seek for potential biomarkers of sleep disorder
      mediated diseases. A label-free quantitative proteomics technology was used to
      survey the global changes of serum proteins between normal rats and chronic sleep
      deprivation rats. A total of 309 proteins were detected in the serum samples and
      among them, 117 proteins showed more than 1.8-folds abundance alterations between
      the two groups. Functional enrichment and network analyses of the differential
      proteins revealed a close relationship between chronic sleep deprivation and
      several biological processes including energy metabolism, cardiovascular function
      and nervous function. And four proteins including pyruvate kinase M1, clusterin,
      kininogen1 and profilin-1were identified as potential biomarkers for chronic
      sleep deprivation. The four candidates were validated via parallel reaction
      monitoring (PRM) based targeted proteomics. In addition, protein expression
      alteration of the four proteins was confirmed in myocardium and brain of rat
      model. In summary, the comprehensive proteomic study revealed the biological
      impacts of chronic sleep deprivation and discovered several potential biomarkers.
      This study provides further insight into the pathological and molecular
      mechanisms underlying sleep disorders at protein level.

PMID- 30235223
TI  - Silk genes and silk gene expression in the spider Tengella perfuga (Zoropsidae),
      including a potential cribellar spidroin (CrSp).
AB  - Most spiders spin multiple types of silk, including silks for reproduction, prey
      capture, and draglines. Spiders are a megadiverse group and the majority of
      spider silks remain uncharacterized. For example, nothing is known about the silk
      molecules of Tengella perfuga, a spider that spins sheet webs lined with
      cribellar silk. Cribellar silk is a type of adhesive capture thread composed of
      numerous fibrils that originate from a specialized plate-like spinning organ
      called the cribellum. The predominant components of spider silks are spidroins,
      members of a protein family synthesized in silk glands. Here, we use silk gland
      RNA-Seq and cDNA libraries to infer T. perfuga silks at the protein level. We
      show that T. perfuga spiders express 13 silk transcripts representing at least
      five categories of spider silk proteins (spidroins). One category is a candidate
      for cribellar silk and is thus named cribellar spidroin (CrSp). Studies of
      ontogenetic changes in web construction and spigot morphology in T. perfuga have
      documented that after sexual maturation, T. perfuga females continue to make
      capture webs but males halt web maintenance and cease spinning cribellar silk.
      Consistent with these observations, our candidate CrSp was expressed only in
      females. The other four spidroin categories correspond to paralogs of aciniform,
      ampullate, pyriform, and tubuliform spidroins. These spidroins are associated
      with egg sac and web construction. Except for the tubuliform spidroin, the
      spidroins from T. perfuga contain novel combinations of amino acid sequence
      motifs that have not been observed before in these spidroin types.
      Characterization of T. perfuga silk genes, particularly CrSp, expand the
      diversity of the spidroin family and inspire new structure/function hypotheses.

PMID- 30235225
TI  - Where in the world is my tweet: Detecting irregular removal patterns on Twitter.
AB  - Twitter data are becoming an important part of modern political science research,
      but key aspects of the inner workings of Twitter streams as well as self
      censorship on the platform require further research. A particularly important
      research agenda is to understand removal rates of politically charged tweets. In
      this article, I provide a strategy to understand removal rates on Twitter,
      particularly on politically charged topics. First, the technical properties of
      Twitter's API that may distort the analyses of removal rates are tested. Results
      show that the forward stream does not capture every possible tweet -between 2 and
      5 percent of tweets are lost on average, even when the volume of tweets is low
      and the firehose not needed. Second, data from Twitter's streams are collected on
      contentious topics such as terrorism or political leaders and non-contentious
      topics such as types of food. The statistical technique used to detect uncommon
      removal rate patterns is multilevel analysis. Results show significant
      differences in the removal of tweets between different topic groups. This article
      provides the first systematic comparison of information loss and removal on
      Twitter as well as a strategy to collect valid removal samples of tweets.

PMID- 30235224
TI  - Comprehensive evaluation of treatment and outcomes of low-grade diffuse gliomas.
AB  - BACKGROUND: Low-grade gliomas affect younger adults and carry a favorable
      prognosis. They include a variety of biological features affecting clinical
      behavior and treatment. Having no guidelines on treatment established, we aim to
      describe clinical and treatment patterns of low-grade gliomas across the largest
      cancer database in the United States. METHODS: We analyzed the National Cancer
      Database from 2004 to 2015, for adult patients with a diagnosis of World Health
      Organization grade II diffuse glioma. RESULTS: We analyzed 13,621 cases with
      median age of 41 years. Over 56% were male, 88.4% were white, 6.1% were black,
      and 7.6% Hispanic. The most common primary site location was the cerebrum
      (79.9%). Overall, 72.2% received surgery, 36.0% radiation, and 27.3%
      chemotherapy. Treatment combinations included surgery only (41.5%), chemotherapy
      + surgery (6.6%), chemotherapy only (3.1%), radiation + chemotherapy + surgery
      (10.7%), radiation + surgery (11.5%), radiation only (6.1%), and radiotherapy +
      chemotherapy (6.7%). Radiation was more common in treatment of elderly patients,
      1p/19q co-deletion (37.3% versus 24.3%, p<0.01), and tumors with midline
      location. Median survival was 11 years with younger age, 1p/19q co-deletion, and
      cerebrum location offered survival advantage. CONCLUSIONS: Tumor location, 1p/19q
      co-deletion, and age were the main determinants of treatment received and
      survival, likely reflecting tumor biology differences. Any form of treatment was
      preferred over watchful waiting in the majority of the patients (86.1% versus
      8.1%). Survival of low-grade gliomas is higher than previously reported in the
      majority of clinical trials and population-based analyses. Our analysis provides
      a real world estimation of treatment decisions, use of molecular data, and
      outcomes.

PMID- 30235227
TI  - Using social network analysis to understand online Problem-Based Learning and
      predict performance.
AB  - Social network analysis (SNA) may be of significant value in studying online
      collaborative learning. SNA can enhance our understanding of the collaborative
      process, predict the under-achievers by means of learning analytics, and uncover
      the role dynamics of learners and teachers alike. As such, it constitutes an
      obvious opportunity to improve learning, inform teachers and stakeholders.
      Besides, it can facilitate data-driven support services for students. This study
      included four courses at Qassim University. Online interaction data were
      collected and processed following a standard data mining technique. The SNA
      parameters relevant to knowledge sharing and construction were calculated on the
      individual and the group level. The analysis included quantitative network
      analysis and visualization, correlation tests as well as predictive and
      explanatory regression models. Our results showed a consistent moderate to strong
      positive correlation between performance, interaction parameters and students'
      centrality measures across all the studied courses, regardless of the subject
      matter. In each of the studied courses, students with stronger ties to prominent
      peers (better social capital) in small interactive and cohesive groups tended to
      do better. The results of correlation tests were confirmed using regression
      tests, which were validated using a next year dataset. Using SNA indicators, we
      were able to classify students according to achievement with high accuracy
      (93.3%). This demonstrates the possibility of using interaction data to predict
      underachievers with reasonable reliability, which is an obvious opportunity for
      intervention and support.

PMID- 30235226
TI  - Continuous veno-venous hemofiltration yields better renal outcomes than
      intermittent hemodialysis among traumatic intracranial hemorrhage patients with
      acute kidney injury: A nationwide population-based retrospective study in Taiwan.
AB  - OBJECT: Traumatic intracranial hemorrhage (TICH) patients with acute kidney
      injury (AKI) were reported to have a high mortality rate. Renal replacement
      therapy (RRT) is indicated for patients with a severe kidney injury. This study
      aimed to compare the effects of different RRT modalities regarding chronic
      dialysis rate among adult TICH patients with AKI. METHODS: A retrospective search
      of computerized hospital records from 2000 to 2010 for patients with a discharge
      diagnosis of TICH was conducted to identify the index cases. We collected the
      data of TICH patients with increased intracranial pressure combined with severe
      AKI who received intermittent hemodialysis (IHD) or continuous veno-venous
      hemofiltration (CVVH) as RRT. The outcome was dialysis dependence between 2000
      and 2010. RESULTS: From a total of 310 patients who were enrolled in the study,
      134 (43%) received CVVH and 176 (57%) received IHD. The risk of dialysis
      dependency was significantly lower in the CVVH group than in the IHD group
      (adjusted hazard ratio: 0.368, 95% CI, 0.158-0.858, P = 0.034). Diabetes mellitus
      and coronary artery disease were risk factors for dialysis dependency. CVVH
      compared with IHD modality was associated with lower dialysis dependency rate in
      TICH patients combined with AKI and diabetes mellitus and those with an injury
      severity score (ISS) >=16. CONCLUSION: CVVH may yield better renal outcomes than
      IHD among TICH patients with AKI, especially those with diabetes mellitus and an
      ISS >=16. The beneficial impact of CVVH on TICH patients needs to be clarified in
      a large cohort study in future.

PMID- 30235228
TI  - Food preferences of similarly raised and kept captive dogs and wolves.
AB  - Food preferences may be driven by a species' ecology. Closely related species
      such as dogs and wolves may have evolved preferences for different foods owing to
      their differing foraging styles. Wolves have been shown to be more persistent in
      problem-solving experiments and more risk-prone in a foraging task. A possible
      element affecting these (and other) results is a potential wolf-dog difference in
      food preferences. To address this possibility, we tested similarly raised and
      kept dogs and wolves in two different food choice tasks, a classic two-choice
      task and a multiple-choice paradigm. We predicted that if dogs have adapted to a
      more opportunistic, scavenging foraging style, they would show a weaker
      preference for meat over starch rich foods (such as kibble) and be less affected
      by hunger than wolves. Alternatively, given the recentness of the new niche dogs
      have created, we predicted no substantial differences between dogs' and wolves'
      food preferences. We found that our subjects did not differ in their preference
      for meat over kibble in either paradigm. However, wolves' (but not dogs') choice
      patterns were affected by satiation, with wolves being less "selective" when
      hungry. Furthermore, when fed before testing, wolves were more selective than
      dogs. These differences were more noticeable in the multiple-choice paradigm than
      the two-choice task, suggesting that the former, novel paradigm may be more
      sensitive and better capable of evaluating food preferences in a diverse range of
      species. Overall, we found that the distinct differences in wolves' and dogs'
      ecology and foraging styles do not appear to have affected their food preferences
      and thus, differences in food preferences are unlikely to have influenced results
      of previous experiments demonstrating wolf-dog differences in cognitive skills.

PMID- 30235231
TI  - Computation of the normalized cross-correlation by fast Fourier transform.
AB  - The normalized cross-correlation (NCC), usually its 2D version, is routinely
      encountered in template matching algorithms, such as in facial recognition,
      motion-tracking, registration in medical imaging, etc. Its rapid computation
      becomes critical in time sensitive applications. Here I develop a scheme for the
      computation of NCC by fast Fourier transform that can favorably compare for speed
      efficiency with other existing techniques and may outperform some of them given
      an appropriate search scenario.

PMID- 30235229
TI  - Physician-related determinants of medical end-of-life decisions - A mortality
      follow-back study in Switzerland.
AB  - BACKGROUND: Medical end-of-life decisions (MELD) and shared decision-making are
      increasingly important issues for a majority of persons at the end of life.
      Little is known, however, about the impact of physician characteristics on these
      practices. We aimed at investigating whether MELDs depend on physician
      characteristics when controlling for patient characteristics and place of death.
      METHODS AND FINDINGS: Using a random sample (N = 8,963) of all deaths aged 1 year
      or older registered in Switzerland between 7 August 2013 and 5 February 2014,
      questionnaires covering MELD details and physicians' demographics, life stance
      and medical formation were sent to certifying physicians. The response rate was
      59.4% (N = 5,328). Determinants of MELDs were analyzed in binary and multinomial
      logistic regression models. MELDs discussed with the patient or relatives were a
      secondary outcome. A total of 3,391 non-sudden nor completely unexpected deaths
      were used, 83% of which were preceded by forgoing treatment(s) and/or intensified
      alleviation of pain/symptoms intending or taking into account shortening of life.
      International medical graduates reported forgoing treatment less often, either
      alone (RRR = 0.30; 95% CI: 0.21-0.41) or combined with the intensified
      alleviation of pain and symptoms (RRR = 0.44; 0.34-0.55). The latter was also
      more prevalent among physicians who graduated in 2000 or later (RRR = 1.60; 1.17
      2.19). MELDs were generally less frequent among physicians with a religious
      affiliation. Shared-decision making was analyzed among 2,542 decedents. MELDs
      were discussed with patient or relatives less frequently when physicians
      graduated abroad (OR = 0.65, 95% CI: 0.50-0.87) and more frequently when
      physicians graduated more recently; physician's sex and religion had no impact.
      CONCLUSIONS: Physicians' characteristics, including the country of medical
      education and time since graduation had a significant effect on the likelihood of
      an MELD and of shared decision-making. These findings call for additional efforts
      in physicians' education and training concerning end-of-life practices and
      improved communication skills.

PMID- 30235230
TI  - DrawingOut - An innovative drawing workshop method to support the generation and
      dissemination of research findings.
AB  - A growing body of literature has explored the potential for arts-based methods to
      generate and disseminate research, particularly on sensitive or complex topics.
      This article presents DrawingOut, a metaphor-centred drawing workshop designed to
      collect visual and textual data about individuals' experiences of sensitive or
      taboo health experiences. The visual data, consisting of the artwork produced by
      participants, and the textual data, all conversations and discussions occurring
      during the workshop, can also be used to create engaging outputs for
      dissemination. We piloted DrawingOut in a study of nine women with a minority
      ethnic or religious background in Cardiff, UK. The women were invited to
      participate in a series of structured drawing activities. The conversations
      occurring during the workshop were recorded and then subjected to thematic
      analysis. Results showed that women's views and experiences could be grouped in
      eight major themes covering their wellbeing, relationship with others, and
      healthcare views and experiences. We produced an A5 16-page booklet that presents
      the pilot study results, illustrated with participants' own drawings and quotes,
      which was disseminated among participants, their community and other relevant
      stakeholders. This pilot study supports the view that healthcare actors can use
      the DrawingOut method to engage people to talk about sensitive health topics,
      while simultaneously providing them with an enjoyable and empowering research
      experience. In our pilot study the DrawingOut was successful in eliciting rich
      visual and textual data that captures a diversity of views and experiences, with
      the added benefit that these can be used to produce engaging outputs for
      dissemination.

PMID- 30235232
TI  - Experimental and computational studies on a protonated 2-pyridinyl moiety and its
      switchable effect for the design of thermolytic devices.
AB  - 1D and 2D NMR investigations as well as computational studies, including static
      quantum-mechanics calculations, density function theory formalism, and classical
      molecular dynamics, were applied to determine the protonation sites in the
      thermolabile protecting group (TPG) containing a 2-pyridynyl moiety within its
      structure. This protecting group has three possible sites for protonation: an
      azomethine (pyridinic) atom (N1), 2-aminoethanol residue (N2), and 4-amino
      substituent (N4). Our investigations showed that the protonation mainly occurs on
      the N1 atom. Such protonation seems to be a major inhibitory factor in the
      thermal removal of 2-pyridynyl TPG by the "chemical switch" approach and
      decreases the aromaticity of the pyridine ring. We also discussed possible
      participation of N2 nitrogen in irreversible intramolecular cyclization under
      acidic conditions.

PMID- 30235233
TI  - A genetic mosaic screen identifies genes modulating Notch signaling in
      Drosophila.
AB  - Notch signaling is conserved in most multicellular organisms and plays critical
      roles during animal development. The core components and major signal
      transduction mechanism of Notch signaling have been extensively studied. However,
      our understanding of how Notch signaling activity is regulated in diverse
      developmental processes still remains incomplete. Here, we report a genetic
      mosaic screen in Drosophila melanogaster that leads to identification of Notch
      signali ng modulators during wing development. We discovered a group of genes
      required for the formation of the fly wing margin, a developmental process that
      is strictly dependent on the balanced Notch signaling activity. These genes
      encode transcription factors, protein phosphatases, vacuolar ATPases and factors
      required for RNA transport, stability, and translation. Our data support the view
      that Notch signaling is controlled through a wide range of molecular processes.
      These results also provide foundations for further study by showing that Me31B
      and Wdr62 function as two novel modulators of Notch signaling activity.

PMID- 30235234
TI  - Systemic immunosuppression and risk of age-related macular degeneration.
AB  - A local immune response has been implicated in the pathogenesis of age-related
      macular degeneration (AMD), but it is unclear if systemic
      immunosuppressive/immunomodulatory therapy (IMT) protects against the onset
      and/or progression of AMD. We performed a retrospective cohort study using a Cox
      proportional hazards model of two cohorts. Cohort 1 included patients with stage
      V chronic kidney disease (CKD) status post kidney transplantation, on at least
      one IMT agent, and older than 50. Cohort 2 included patients with stage IV or V
      CKD who had not undergone kidney transplantation, were not on IMT, and were older
      than 50. The main outcomes were hazard ratios of a new diagnosis of dry AMD, wet
      AMD, or conversion from dry to wet. There were 10,813 patients in cohort 1, and
      217,081 patients in cohort 2. After controlling for sex and age, there was no
      significant difference in the hazard of developing a new diagnosis of dry AMD (HR
      = 0.95, 95% CI 0.87-1.05, p = 0.32), developing a new diagnosis of wet AMD
      without any prior diagnosis of dry AMD (HR = 0.85, 95% CI 0.66-1.08, p = 0.18),
      or converting from dry to wet AMD (HR 1.24, 95% CI 0.94-1.62, p = 0.12). For
      patients over 70 on mycophenolate mofetil, there was a reduced hazard of
      converting from dry to wet AMD (HR = 0.92, 95% CI = 0.85-0.99, p = 0.02). In
      contrast, everolimus had an increased hazard of dry AMD (HR = 2.14, 95% CI 1.24
      3.69, p < 0.01). Most systemic IMT does not affect the risk of onset or
      progression of AMD in patients with CKD. However, mycophenolate mofetil may
      confer some degree of protection against the conversion of dry AMD to wet AMD,
      suggesting that modulation of the immune response may prevent progression of the
      disease.

PMID- 30235235
TI  - Intravenous sildenafil acutely improves hemodynamic response to exercise in
      patients with connective tissue disease.
AB  - BACKGROUND: Hemodynamic assessment during exercise may unmask an impaired
      functional reserve of the right ventricle and the pulmonary vasculature in
      patients with connective tissue disease. We assessed the effect of intravenous
      sildenafil on the hemodynamic response to exercise in patients with connective
      tissue disease. METHODS: In this proof-of-concept study, patients with connective
      tissue disease and mean pulmonary arterial pressure (mPAP) >20 mm Hg were
      subjected to a supine exercise hemodynamic evaluation before and after
      administration of intravenous sildenafil 10 mg. RESULTS: Ten patients (four with
      moderately elevated mPAP 21-24 mm Hg; six with mPAP >25 mm Hg) underwent
      hemodynamic assessment. All of them showed markedly abnormal exercise
      hemodynamics. Intravenous sildenafil was well tolerated and had significant
      hemodynamic effects at rest and during exercise, although without pulmonary
      selectivity. Sildenafil reduced median total pulmonary resistance during exercise
      from 6.22 (IQR 4.61-8.54) to 5.24 (3.95-6.96) mm Hg.min.L-1 (p = 0.005) and
      increased median pulmonary arterial capacitance during exercise from 1.59 (0.93
      2.28) to 1.74 (1.12-2.69) mL/mm Hg (p = 0.005). CONCLUSIONS: In patients with
      connective tissue disease who have an abnormal hemodynamic response to exercise,
      intravenous sildenafil improved adaption of the right ventricular-pulmonary
      vascular unit to exercise independent of resting mPAP. The impact of acute
      pharmacological interventions on exercise hemodynamics in patients with pulmonary
      vascular disease warrants further investigation. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01889966.

PMID- 30235236
TI  - TFDP3 regulates the apoptosis and autophagy in breast cancer cell line MDA-MB
      231.
AB  - Cancer/testis antigen TFDP3 belongs to the transcription factor DP(TFDP) family.
      It can bind to E2F family molecules to form a heterodimeric transcription factor
      E2F/TFDP complex. The complex is an important regulatory activator of cell cycle,
      involved in the regulation of cell proliferation, differentiation, apoptosis and
      other important physiological activities. In addition, TFDP3 has also been found
      to be a tumor-associated antigen that only expresses in malignant tumor tissue
      and normal testicular tissue; Thus, it is closely related to tumor occurrence and
      development. In this study, our group investigated the expression of TFDP3 in
      mononuclear cell samples from a variety of tissue-derived malignant tumors,
      breast cancer and benign breast lesions. The results show that TFDP3 is expressed
      in the malignant form of various tissues. Moreover, our recent research had
      focused on the ability of TFDP3 to influence the drug resistance and apoptosis of
      tumor cells. To further clarify the mechanisms involved in tumor resistance, this
      study also examined the expression of TFDP3 and tumor cell autophagy regulation;
      Autophagy helps cells cope with metabolic stress (such as in cases of
      malnutrition, growth factor depletion, hypoxia or hypoxia) removes erroneously
      folded proteins or defective organelles to prevent the accumulation of abnormal
      proteins; and removes intracellular pathogens. Our results showed that TFDP3
      expression can induce autophagy by up-regulating the expression of autophagic key
      protein LC3(MAP1LC3) and increasing the number of autophagosomes during
      chemotherapy of malignant tumors. Then, DNA and organelles damage caused by the
      chemotherapy medicine are repaired. Thus, TFDP3 contributes toward tumor cell
      resistance. When siRNA inhibits TFDP3 expression, it can reduce cell autophagy,
      improving the sensitivity of tumor cells to chemotherapy drugs.

PMID- 30235237
TI  - Uncertainties of potentials and recent changes in global yields of major crops
      resulting from census- and satellite-based yield datasets at multiple
      resolutions.
AB  - Global agriculture is under pressure to meet increasing demand for food and
      agricultural products. There are several global assessments of crop yields, but
      we know little about the uncertainties of their key findings, as the assessments
      are driven by the single best yield dataset available when each assessment was
      conducted. Recently, two different spatially explicit, global, historical yield
      datasets, one based on agricultural census and the other largely based on
      satellite remote sensing, became available. Using these datasets, we compare the
      similarities and differences in global yield gaps, trend patterns, growth rates
      and changes in year-to-year variability. We analyzed maize, rice, wheat and
      soybean for the period of 1981 to 2008 at four resolutions (0.083 degrees , 0.5
      degrees , 1.0 degrees  and 2.0 degrees ). Although estimates varied by dataset
      and resolution, the global mean annual growth rates of 1.7-1.8%, 1.5-1.7%, 1.1
      1.3% and 1.4-1.6% for maize, rice, wheat and soybean, respectively, are not on
      track to double crop production by 2050. Potential production increases that can
      be attributed to closing yield gaps estimated from the satellite-based dataset
      are almost twice those estimated from the census-based dataset. Detected yield
      variability changes in rice and wheat are sensitive to the choice of dataset and
      resolution, but they are relatively robust for maize and soybean. Estimates of
      yield gaps and variability changes are more uncertain than those of yield trend
      patterns and growth rates. These tendencies are consistent across crops. Efforts
      to reduce uncertainties are required to gain a better understanding of historical
      change and crop production potential to better inform agricultural policies and
      investments.

PMID- 30235238
TI  - An Enhanced Region Proposal Network for object detection using deep learning
      method.
AB  - Faster Region-based Convolutional Network (Faster R-CNN) is a state-of-the-art
      object detection method. However, the object detection effect of Faster R-CNN is
      not good based on the Region Proposal Network (RPN). Inspired by RPN of Faster R
      CNN, we propose a novel proposal generation method called Enhanced Region
      Proposal Network (ERPN). Four improvements are presented in ERPN. Firstly, our
      proposed deconvolutional feature pyramid network (DFPN) is introduced to improve
      the quality of region proposals. Secondly, novel anchor boxes are designed with
      interspersed scales and adaptive aspect ratios. Thereafter, the capability of
      object localization is increased. Thirdly, a particle swarm optimization (PSO)
      based support vector machine (SVM), termed PSO-SVM, is developed to distinguish
      the positive and negative anchor boxes. Fourthly, the classification part of
      multi-task loss function in RPN is improved. Consequently, the effect of
      classification loss is strengthened. In this study, our proposed ERPN is compared
      with five object detection methods on both PASCAL VOC and COCO data sets. For the
      VGG-16 model, our ERPN obtains 78.6% mAP on VOC 2007 data set, 74.4% mAP on VOC
      2012 data set and 31.7% on COCO data set. The performance of ERPN is the best
      among the comparison object detection methods. Furthermore, the detection speed
      of ERPN is 5.8 fps. Additionally, ERPN obtains good effect on small object
      detection.

PMID- 30235239
TI  - Echo chambers and viral misinformation: Modeling fake news as complex contagion.
AB  - The viral spread of digital misinformation has become so severe that the World
      Economic Forum considers it among the main threats to human society. This spread
      have been suggested to be related to the similarly problematized phenomenon of
      "echo chambers", but the causal nature of this relationship has proven difficult
      to disentangle due to the connected nature of social media, whose causality is
      characterized by complexity, non-linearity and emergence. This paper uses a
      network simulation model to study a possible relationship between echo chambers
      and the viral spread of misinformation. It finds an "echo chamber effect": the
      presence of an opinion and network polarized cluster of nodes in a network
      contributes to the diffusion of complex contagions, and there is a synergetic
      effect between opinion and network polarization on the virality of
      misinformation. The echo chambers effect likely comes from that they form the
      initial bandwagon for diffusion. These findings have implication for the study of
      the media logic of new social media.

PMID- 30235240
TI  - Spatial-seasonal characteristics and critical impact factors of PM2.5
      concentration in the Beijing-Tianjin-Hebei urban agglomeration.
AB  - As China's political and economic centre, the Beijing-Tianjin-Hebei (BTH) urban
      agglomeration experiences serious environmental challenges on particulate matter
      (PM) concentration, which results in fundamental or irreparable damages in
      various socioeconomic aspects. This study investigates the seasonal and spatial
      distribution characteristics of PM2.5 concentration in the BTH urban
      agglomeration and their critical impact factors. Spatial interpolation are used
      to analyse the real-time monitoring of PM2.5 data in BTH from December 2013 to
      May 2017, and partial least squares regression is applied to investigate the
      latest data of potential polluting variables in 2015. Several important findings
      are obtained: (1) Notable differences exist amongst PM2.5 concentrations in
      different seasons; January (133.10 mg/m3) and December (120.19 mg/m3) are the
      most polluted months, whereas July (38.76 mg/m3) and August (41.31 mg/m3) are the
      least polluted months. PM2.5 concentration shows a periodic U-shaped variation
      pattern with high pollution levels in autumn and winter and low levels in spring
      and summer. (2) In terms of spatial distribution characteristics, the most highly
      polluted areas are located south and east of the BTH urban agglomeration, and
      PM2.5 concentration is significantly low in the north. (3) Empirical results
      demonstrate that the deterioration of PM2.5 concentration in 2015 is closely
      related to a set of critical impact factors, including population density,
      urbanisation rate, road freight volume, secondary industry gross domestic
      product, overall energy consumption and industrial pollutants, such as steel
      production and volume of sulphur dioxide emission, which are ranked in terms of
      their contributing powers. The findings provide a basis for the causes and
      conditions of PM2.5 pollution in the BTH regions. Viable policy recommendations
      are provided for effective air pollution treatment.

PMID- 30235241
TI  - The impact of height-adjustable desks and prompts to break-up classroom sitting
      on adolescents' energy expenditure, adiposity markers and perceived
      musculoskeletal discomfort.
AB  - Adolescents spend large amounts of time sitting at school. Little is known about
      the impact of reducing and breaking-up prolonged sitting during school lessons on
      adolescents' health. This study aimed to investigate the impact of an
      intervention to reduce classroom sitting time on adolescents' energy expenditure
      (EE; kcal/lesson), body mass index (BMI), waist circumference (WC), and
      musculoskeletal discomfort. A secondary school classroom was equipped with height
      adjustable desks, posters promoting the health benefits of and strategies for
      breaking-up sitting time, and desk stickers reminding students to periodically
      stand up. Classroom teachers participated in a professional development session.
      Using a quasi-experimental design, differences between 49 participants who
      utilised the intervention classroom 2-5 times/week and a comparison group (39
      adolescents, matched by year level and subject) who used traditional classrooms,
      were examined. EE, BMI and WC were objectively measured and musculoskeletal
      discomfort was self-reported at baseline, 4-weeks, and 17-weeks. Hierarchical
      linear and multilevel logistic regression-mixed models were used to examine
      intervention effects, adjusting for baseline values, sex and age. EE was
      significantly higher at 4-weeks and 17-weeks (29.4 and 37.7 kcal/lesson,
      respectively), BMI was higher at 4-weeks (0.34 kg/m2), and WC was lower at 4
      weeks and 17-weeks (-3.53 and -2.64 cm, respectively) in the intervention
      compared to the comparison group. No intervention effect was found for
      musculoskeletal discomfort. Findings provide preliminary indications that these
      strategies may benefit health among adolescents in the short term. However,
      extended longer-duration trials are needed to determine longer-term health
      effects.

PMID- 30235242
TI  - Anisakis sensitization in different population groups and public health impact: A
      systematic review.
AB  - Anisakis simplex spp. sensitization rates have increased worldwide, with a
      significant impact on health-care systems. To date, no clear-cut diagnostic
      criteria and laboratory algorithm have been established, so anisakiasis still
      represents an under-reported health problem whose clinical manifestations, when
      present, mimic the much more common allergic and digestive disorders. Aim of the
      study was to systematically review the available literature on the prevalence of
      sensitization against Anisakis in the general population and in specific
      population groups, taking into account the impact of the different available
      diagnostic techniques on the epidemiological data. Following the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement,
      relevant papers reporting Anisakis sensitization epidemiological data were found
      covering a period ranging from 1996 to February 2017. Overall, 41 studies
      comprising 31,701 participants from eleven countries were included in the
      qualitative synthesis. General asymptomatic population resulted sensitized to
      Anisakis in 0.4 to 27.4% of cases detected by means of indirect ELISA or
      ImmunoCAP specific IgE detection, and between 6.6% and 19.6% of the samples by
      Skin prick test (SPT). Occupationally exposed workers (fishermen, fishmongers and
      workers of fish-processing industries) documented specific IgE between 11.7% and
      50% of cases, whereas SPT positivity ranged between 8% and 46.4%. Symptomatic
      allergic patients to any kind of allergen were found to be positive to Anisakis
      specific IgE detection between 0.0% (in children with mastocytosis) to 81.3%
      (among adults with shellfish allergy). Results highlighted that hypersensitivity
      prevalence estimates varied widely according to geographical area,
      characteristics of the population studied, diagnostic criteria and laboratory
      assays. Further studies are needed to overcome the documented misdiagnosis by
      improving the diagnostic approach and, consequently, providing more affordable
      estimates in order to address public health interventions on populations at high
      risk of exposure to Anisakis and to tailor health services related to specific
      groups.

PMID- 30235243
TI  - Reverse taxonomy applied to the Brachionus calyciflorus cryptic species complex:
      Morphometric analysis confirms species delimitations revealed by molecular
      phylogenetic analysis and allows the (re)description of four species.
AB  - The discovery and exploration of cryptic species have been profoundly expedited
      thanks to developments in molecular biology and phylogenetics. In this study, we
      apply a reverse taxonomy approach to the Brachionus calyciflorus species complex,
      a commonly studied freshwater monogonont rotifer. By combining phylogenetic,
      morphometric and morphological analyses, we confirm the existence of four cryptic
      species that have been recently suggested by a molecular study. Based on these
      results and according to an exhaustive review of the taxonomic literature, we
      name each of these four species and provide their taxonomic description alongside
      a diagnostic key.

PMID- 30235244
TI  - No difference in effectiveness of treatment simplification to boosted or
      unboosted atazanavir plus lamivudine in virologically suppressed in HIV-1
      infected patients.
AB  - BACKGROUND: Simplification strategies of antiretroviral treatment represent
      effective tools for the reduction of drug-induced toxicity, resistance mutations
      in case of virological failure and costs. OBJECTIVES: To assess the effectiveness
      of simplification to atazanavir/ritonavir (ATVrtv) or unboosted atazanavir
      (ATV400) plus lamivudine, and if low plasma or intracellular ATV Ctrough
      influence virological outcomes. METHODS: Ambispective observational study in
      patients with undetectable HIV-RNA who were switched to ATVrtv or ATV400 plus
      lamivudine once daily. Previous virological failures (VF) were allowed if the
      resistance tests showed major resistance mutation neither to ATV nor to
      lamivudine. VF was defined as two consecutive plasma HIV-RNA >200 copies/mL.
      Effectiveness was assessed by intention-to-treat and on-treatment analyses.
      Plasma and intracellular ATV Ctrough were measured by LC-MS/MS. RESULT: A total
      of 246 patients were included. At week 48, the Kaplan-Meier estimation of
      efficacy within the ATVrtv and ATV400 groups were 85.9% [95% confidence interval,
      (CI95), 80.3-91.4%] versus 87.6% (CI95, 80.1-94.1%) by intention-to-treat
      analysis (p = 0.684), and 97.7% (CI95, 95.2-100%) versus 98.8% (CI95, 97.0-100%)
      by on-treatment analysis (p = 0.546), respectively. Plasma and intracellular
      Ctrough were significantly higher with ATVrtv than with ATV400 (geometric mean
      (GM), 318.3 vs. 605.9 ng/mL; p = 0.013) and (811.3 vs. 2659.2 ng/mL; p = 0.001),
      respectively. Only 14 patients had plasma Ctrough below the suggested effective
      concentration for ATV (150 ng/mL). No relationship between plasma or
      intracellular Ctrough and VF or blips were found. CONCLUSION: Boosted or
      unboosted ATV plus lamivudine is effective and safe, and the lower plasma Ctrough
      observed with ATV400 do not compromise the effectiveness of these simplification
      regimens in long-term virologically suppressed HIV-1-infected patients.

PMID- 30235245
TI  - Evaluation of surfactant proteins A, B, C, and D in articular cartilage, synovial
      membrane and synovial fluid of healthy as well as patients with osteoarthritis
      and rheumatoid arthritis.
AB  - OBJECTIVE: Surfactant Proteins (SPs) are well known from lung and form, along
      with phospholipids, a surface-active-layer at the liquid-air-interface of the
      alveolar lining. They play a major protective role by lowering surface tension,
      activating innate and adaptive immune defense at the lung mucosal interface,
      especially during infection. We analyzed the regulation of SPs in human and mouse
      articular chondrocytes, synoviocytes, and synovial fluid under healthy and
      inflammatory conditions, as well as in tissues of patients suffering from
      osteoarthritis and rheumatoid arthritis. METHODS: Immunohistochemistry, RT-PCR,
      qRT-PCR, ELISA, Western blotting were performed in cell cultures and tissue
      samples to determine localization, regulation, and concentration of SPs. RESULTS:
      All four SPs, were expressed by healthy human and mouse articular chondrocytes
      and synoviocytes and were also present in synovial fluid. Treatment with
      inflammatory mediators like IL-1beta and TNF-alpha led to short-term upregulation
      of individual SPs in vitro. In tissues from patients with osteoarthritis and
      rheumatoid arthritis, protein levels of all four SPs increased significantly
      compared to the controls used. CONCLUSION: These results show the distribution
      and amount of SPs in tissues of articular joints. They are produced by
      chondrocytes and synoviocytes and occur in measurable amounts in synovial fluid.
      All four SPs seem to be differently regulated under pathologic conditions. Their
      physiological functions in lowering surface tension and immune defense need
      further elucidation and make them potential candidates for therapeutic
      intervention.

PMID- 30235246
TI  - A qualitative exploration of post-acute stroke participants' experiences of a
      multimodal intervention incorporating horseback riding.
AB  - BACKGROUND: Multimodal rehabilitation interventions delivered in late phase of
      stroke recovery involve physical (motor and sensory), social, and cognitively
      challenging activities. Horseback riding can be incorporated within such
      interventions, leading to meaningful long-term improvements when applied to
      individuals with moderate levels of disability. There is a lack of research
      illuminating stroke survivors' experiences and perceptions of horseback riding in
      the context of multimodal interventions. AIM: To explore stroke survivors'
      experiences of participation in a multimodal group-based intervention that
      included horseback riding. METHODS: An explorative interview study was conducted
      with individual face-to-face interviews performed on a single occasion, utilising
      a semi-structured interview guide. Eighteen participants were purposively
      selected from a larger trial (mean age 62, 12 men, 6 women) within four weeks
      after treatment completion. The interview duration was between 17 and 50 minutes.
      The data was analysed using a qualitative content analysis method. FINDINGS: Four
      broad themes were identified from the analysis. These themes were: transformative
      experiences; human-horse interaction; togetherness and belonging; and the all-in
      one solution. Interacting with the horse and peers had a profound emotional
      impact on the participants. The participants also reported having learned new
      skills, increased self-efficacy and self-esteem, and improvements in balance and
      gait, all of which could be transferred to everyday life. The horse itself played
      a central role, but other components, such as the other group members, the
      instructors, and the challenging tasks on the horseback, were also important.
      CONCLUSION: A multimodal rehabilitation intervention that includes horseback
      riding may provide stroke survivors in a late phase of recovery with rich
      pleasurable experiences that may have life-changing and profound impacts on their
      emotional and physical state.

PMID- 30235248
TI  - Flow field characteristics and coal dust removal performance of an arc fan nozzle
      used for water spray.
AB  - Dust source that presents a ring shape is frequently observed in mining
      engineering. An arc fan nozzle used for water spray is designed to improve the
      dust removal efficiency. Based on a study of the spray field characteristics of
      an arc fan nozzle using volume of fluid (VOF) analysis, it is found that the
      section of arc fan flow gradually increases, and its mean width of the impact
      zone is 3.1 times that of the free jet zone. After leaving the guiding object,
      the central axis velocity of the arc fan flow rapidly increases and then
      gradually decreases. Based on dimensionless analysis, the calculation formula of
      the jet speed near the wall is achieved. The relationship between the section
      geometric features of arc fan flow and the structural parameters of the arc fan
      nozzle is analysed. A field test completed in the Fucun coal mine indicates that
      the dust removal efficiency obviously improved with the use of arc fan nozzles.
      Compared to the full cone nozzles used before, the average removal efficiency for
      total dust increased by 34%, and the average removal efficiency for respirable
      dust increased by 32%.

PMID- 30235247
TI  - Combination therapy for treatment of Pseudomonas aeruginosa bloodstream
      infections.
AB  - OBJECTIVES: Management of bloodstream infections ("BSIs") caused by Pseudomonas
      aeruginosa remains controversial as data supporting the use of definite
      combination treatment for severe P. aeruginosa infections remain conflicting. We
      aimed to determine differences in mortality between patients treated with
      definite combination therapy and monotherapy in a large 11-year cohort. METHODS:
      All consecutive patients with P. aeruginosa BSI hospitalized at the University
      Hospital Basel, Switzerland, a tertiary academic care center, from January 2003
      to December 2013 were included. Pertinent clinical data was assessed. Patients
      with and without definite combination therapy were compared and hazard ratios for
      death were calculated. RESULTS: During the study period, 187 patients with P.
      aeruginosa BSI were identified. Definite combination therapy was administered in
      42.8% (80/187) of all patients, of which 76% (61/80) received a combination of a
      betalactam with an aminoglycoside and 24% (19/80) received a combination of a
      betalactam with a quinolone. The remaining 57.2% (107/187) were treated with
      betalactam monotherapy. Median treatment duration was 15 days (interquartile
      range 12-20 days). Mortality was lower in patients receiving definite combination
      therapy in univariable and multivariable cox regression analyses (HR 0.26, 95% CI
      0.11-0.60, p = 0.002 and HR 0.30, 95% CI 0.13-0.71, p = 0.006, respectively), the
      latter adjusting for age, neutropenia at diagnosis, PITT bacteremia score, and
      inadequate empirical treatment. CONCLUSIONS: Combination therapy (i.e. betalactam
      aminoglycoside or betalactam-quinolone combinations) may improve survival of P.
      aeruginosa BSI, independent of potential confounders such as age, neutropenia,
      PITT bacteremia score, and inadequate empirical treatment.

PMID- 30235250
TI  - Locomotor adaptations to prolonged step-by-step frontal plane trunk perturbations
      in young adults.
AB  - The purpose of this study was to quantify the magnitude and time course of
      dynamic balance control adaptations to prolonged step-by-step frontal plane
      forces applied to the trunk during walking. Healthy young participants (n = 10, 5
      female) walked on an instrumented split-belt treadmill while an external cable
      driven device applied frontal plane forces to the trunk. Two types of forces were
      applied: 1) forces which accentuated COM movement in the frontal plane
      (destabilizing) and 2) forces which resisted COM movement in the frontal plane
      (stabilizing). We quantified dynamic balance control using frontal plane measures
      of (1) the extent of center of mass (COM) movement over a gait cycle (COM sway),
      (2) the magnitude of base of support (step width), and (3) cadence. During
      destabilizing force conditions, COM sway, step width, and cadence increased. In
      response to stabilizing force conditions, COM sway decreased. In addition, during
      destabilizing balance conditions participants made quicker adaptations to their
      step width compared to the time to adapt to stabilizing forces. Taken together,
      these results provide important insight into differences in dynamic balance
      control strategies in response to stabilizing and destabilizing force fields.

PMID- 30235251
TI  - Spatial distribution of Taenia solium exposure in humans and pigs in the Central
      Highlands of Vietnam.
AB  - BACKGROUND: Taenia solium, a pork-borne parasitic zoonosis, is the cause of
      taeniasis and cysticercosis in humans. In Vietnam, poor sanitation, the practice
      of outdoor defecation and consumption of raw/undercooked pork have been
      associated with infection/exposure to T. solium in both humans and pigs. The
      broad-scale geographic distribution of the prevalence of T. solium varies
      throughout the country with infection restricted to isolated foci in the north
      and a more sporadic geographic distribution in the Central Highlands and the
      south. While cross-sectional studies have allowed the broad-scale geographic
      distribution of T. solium to be described, details of the geographic distribution
      of T. solium at finer spatial scales have not been described in detail. This
      study provides a descriptive spatial analysis of T. solium exposure in humans and
      pigs and T. solium taeniasis in humans within individual households in village
      communities of Dak Lak in the Central Highlands of Vietnam. METHODOLOGY/PRINCIPAL
      FINDINGS: We used Ripley's K-function to describe spatial dependence in T. solium
      exposure positive and negative human and pig households and T. solium taeniasis
      exposure positive and negative households in villages within the districts of
      Buon Don, Krong Nang and M'Drak of Dak Lak province in the Central Highlands of
      Vietnam. The prevalence of exposure to T. solium in pigs in Dak Lak province was
      9 (95% CI 5 to 17) cases per 1000 pigs at risk. The prevalence of exposure to the
      parasite in humans was somewhat higher at 5 (95% CI 3 to 8) cases per 100
      individuals at risk. Spatial aggregations of T. solium exposure-positive pig and
      human households occurred in some, but not all of the villages in the three study
      districts. Human exposure-positive households were found to be aggregated within
      a distance of 200 to 300 m in villages in Krong Nang district compared with
      distances of up to 1500 m for pig exposure-positive households in villages in
      M'Drak district. Although this study demonstrated the aggregation of households
      in which either T. solium exposure- or taeniasis-positive individuals were
      present, we were unable to identify an association between the two due to the
      very low number of T. solium taeniasis-positive households. CONCLUSIONS: Spatial
      aggregations of T. solium exposure-positive pig and human households occurred in
      some, but not all of the villages in the three study districts. We were unable to
      definitively identify reasons for these findings but speculate that they were due
      to a combination of demographic, anthropological and micro-environmental factors.
      To more definitively identify characteristics that increase cysticercosis risk we
      propose that cross-sectional studies similar in design to that described in this
      paper should be applied in other provinces of Vietnam.

PMID- 30235252
TI  - Detection, virulence and genetic diversity of Fusarium species infecting tomato
      in Northern Pakistan.
AB  - In addition to the well-known Fusarium oxysporum f.sp. lycopersici, several other
      Fusarium species are known to cause extensive worldwide crop losses in tomatoes.
      Prevalence and identities of Fusarium species infecting tomatoes in Northwest
      Pakistan is currently not known. In this study, we surveyed and characterized
      Fusarium species associated with symptomatic tomatoes in Northwest Pakistan using
      morphological and molecular analyses. Pathogenicity tests revealed varying
      degrees of virulence with some Fusarium sp. causing severe disease symptoms
      whereas others displaying mild symptoms. Molecular identification based on
      Internal Transcribed Spacer (ITS) region and TEF-1alpha gene sequencing
      classified all isolates into four major species with a majority (68.9%) belonging
      to Fusarium incarnatum-equiseti species complex (FIESC), followed by F.
      graminearum (20.7%), F. acuminatum (6.8%), and F. solani (6.8%). ISSR analyses
      revealed substantial genetic variability among all the Fusarium population
      infecting tomatoes. Genetic distance between populations from the central region
      and the type strain F.o. f.sp. lycopersici from Florida was the highest (0.3662),
      whereas between the south and central region was the lowest (0.0298), which
      showed that genetic exchange is negatively effected by distance. High genetic
      variability suggests that these Fusarium species have the potential to become a
      major production constraint for tomato growers. Findings in this report would
      greatly facilitate identification of Fusarium species in developing countries and
      would provide groundwork for devising and implementing disease management
      measures for minimizing losses caused by Fusarium species in tomatoes.

PMID- 30235249
TI  - Heterozygous junctophilin-2 (JPH2) p.(Thr161Lys) is a monogenic cause for HCM
      with heart failure.
AB  - During the last two decades, mutations in sarcomere genes have found to comprise
      the most common cause for hypertrophic cardiomyopathy (HCM), but still
      significant number of patients with dominant HCM in the family are left without
      molecular genetic diagnosis. Next generation sequencing (NGS) does not only
      enable evaluation of established HCM genes but also candidate genes for
      cardiomyopathy are frequently tested which may lead to a situation where
      conclusive interpretation of the variant requires extensive family studies. We
      aimed to characterize the phenotype related to a variant in the junctophilin-2
      (JPH2) gene, which is less known non-sarcomeric candidate gene. In addition, we
      did extensive review of the literature and databases about JPH2 variation in
      association with cardiac disease. We characterize nine Finnish index patients
      with HCM and heterozygous for JPH2 c.482C>A, p.(Thr161Lys) variant were included
      and segregation studies were performed. We identified 20 individuals affected
      with HCM with or without systolic heart failure and conduction abnormalities in
      the nine Finnish families with JPH2 p.(Thr161Lys) variant. We found 26
      heterozygotes with the variant and penetrance was 71% by age 60 and 100% by age
      80. Co-segregation of the variant with HCM phenotype was observed in six
      families. Main clinical features were left ventricular hypertrophy, arrhythmia
      vulnerability and conduction abnormalities including third degree AV-block. In
      some patients end-stage severe left ventricular heart failure with normal or
      mildly enlarged diastolic dimensions was detected. In conclusion, we propose that
      the heterozygous JPH2 p.(Thr161Lys) variant is a new Finnish mutation causing
      atypical HCM.

PMID- 30235253
TI  - Deep learning-based quantification of abdominal fat on magnetic resonance images.
AB  - Obesity is increasingly prevalent and associated with increased risk of
      developing type 2 diabetes, cardiovascular diseases, and cancer. Magnetic
      resonance imaging (MRI) is an accurate method for determination of body fat
      volume and distribution. However, quantifying body fat from numerous MRI slices
      is tedious and time-consuming. Here we developed a deep learning-based method for
      measuring visceral and subcutaneous fat in the abdominal region of mice. Congenic
      mice only differ from C57BL/6 (B6) Apoe knockout (Apoe-/-) mice in chromosome 9
      that is replaced by C3H/HeJ genome. Male congenic mice had lighter body weight
      than B6-Apoe-/- mice after being fed 14 weeks of Western diet. Axial and coronal
      T1-weighted sequencing at 1-mm-thickness and 1-mm-gap was acquired with a 7T
      Bruker ClinScan scanner. A deep learning approach was developed for segmenting
      visceral and subcutaneous fat based on the U-net architecture made publicly
      available through the open-source ANTsRNet library-a growing repository of well
      known neural networks. The volumes of subcutaneous and visceral fat measured
      through our approach were highly comparable with those from manual measurements.
      The Dice score, root-mean-square error (RMSE), and correlation analysis
      demonstrated the similarity between two methods in quantifying visceral and
      subcutaneous fat. Analysis with the automated method showed significant
      reductions in volumes of visceral and subcutaneous fat but not non-fat tissues in
      congenic mice compared to B6 mice. These results demonstrate the accuracy of deep
      learning in quantification of abdominal fat and its significance in determining
      body weight.

PMID- 30235254
TI  - Hypoxia modulates the antioxidant effect of hydroxytyrosol in MCF-7 breast cancer
      cells.
AB  - Although cancer is multifactorial, a strong correlation between this pathology
      and increased oxidative stress has long been stablished. Hypoxia, inherent to
      solid tumors, increases reactive oxygen species and should be taken into account
      when analyzing the response of tumor cells to antioxidants. The Mediterranean
      diet has been related to a lower incidence of cancer, and particularly of breast
      cancer. Given that hydroxytyrosol (HT) is largely responsible for the antioxidant
      properties of olive oil, we have performed a comprehensive and comparative study
      of its effect on the oxidative stress response of the human breast cancer cell
      line MCF-7 in hypoxia and normoxia. Our results demonstrate that the antioxidant
      action of HT is particularly effective in a hypoxic environment. Moreover, we
      have observed that this polyphenol modulates the transcription and translation of
      members of the PGC-1alpha/ERRalpha and PGC-1alpha/Nrf2 pathways. However, while
      the transcriptional effects of HT are similar in normoxic and hypoxic conditions,
      its translational action is less prominent and partially attenuated in hypoxia,
      and therefore cannot completely explain the antioxidant effect of HT.
      Consequently, our results underscore that the hypoxic environment of tumor cells
      should be considered when analyzing the effect of bioactive compounds. Besides,
      this study also points to the importance of assessing the regulatory role of HT
      at both mRNA and protein level to get a complete picture of its effects.

PMID- 30235255
TI  - Workplace psychosocial stressors experienced by migrant workers in Australia: A
      cross-sectional study.
AB  - OBJECTIVE: To explore work-related psychosocial stressors among people of
      Chinese, Vietnamese and Arabic-speaking backgrounds currently working in
      Australia. METHODS: In 2015, a telephone survey of 585 Vietnamese, Chinese and
      Arabic-speaking workers asked about workplace bullying, ethnic discrimination,
      job complexity, degree of control, security and fairness of payment along with
      demographic and employment information. Estimates of job-related psychosocial
      stressors were derived and regression analyses used to identify significant
      associations. RESULTS: At least one workplace stressor was reported by 83% of the
      workers in the study. Education was significantly associated with experiencing
      any psychosocial stressor and also with the total number of stressors. Workers
      aged 45 years and older were more likely to be bullied or experience racial
      discrimination compared with younger workers of any ethnicity. There was a
      greater likelihood of reporting low control over a job when the interview was
      conducted in a language other than English and the workers were either Chinese or
      Arabic. Workers on a fixed-term contract, independent of ethnicity were more
      likely to report a job with low security. Overall psychosocial job quality
      decreased with education and was associated with occupation type which interacted
      with ethnicity and gender. CONCLUSIONS: The results suggest that job-related
      psychosocial stressors are widespread but not uniform across ethnic groups.
      Further research into what drives differences in work experience for migrant
      groups would provide information to guide both employers and migrants in ways to
      reduce workplace psychosocial stressors.

PMID- 30235256
TI  - Exogenous C-type natriuretic peptide restores normal growth and prevents early
      growth plate closure in its deficient rats.
AB  - Signaling by C-type natriuretic peptide (CNP) and its receptor, natriuretic
      peptide receptor-B, is a pivotal stimulator of endochondral bone growth. We
      recently developed CNP knockout (KO) rats that exhibit impaired skeletal growth
      with early growth plate closure. In the current study, we further characterized
      the phenotype and growth plate morphology in CNP-KO rats, and the effects of
      exogenous CNP in rats. We used CNP-53, an endogenous form of CNP consisting of 53
      amino acids, and administered it for four weeks by continuous subcutaneous
      infusion at 0.15 or 0.5 mg/kg/day to four-week old CNP-KO and littermate wild
      type (WT) rats. We demonstrated that CNP-KO rats were useful as a reproducible
      animal model for skeletal dysplasia, due to their impairment in endochondral bone
      growth. There was no significant difference in plasma bone-turnover markers
      between the CNP-KO and WT rats. At eight weeks of age, growth plate closure was
      observed in the distal end of the tibia and the calcaneus of CNP-KO rats.
      Continuous subcutaneous infusion of CNP-53 significantly, and in a dose-dependent
      manner, stimulated skeletal growth in CNP-KO and WT rats, with CNP-KO rats being
      more sensitive to the treatment. CNP-53 also normalized the length of long bones
      and the growth plate thickness, and prevented growth plate closure in the CNP-KO
      rats. Using organ culture experiment of fetal rat tibia, gene set enrichment
      analysis indicated that CNP might have a negative influence on mitogen activated
      protein kinase signaling cascades in chondrocyte. Our results indicated that CNP
      KO rats might be a valuable animal model for investigating growth plate
      physiology and the mechanism of growth plate closure, and that CNP-53, or its
      analog, may have the potential to promote growth and to prevent early growth
      plate closure in the short stature.

PMID- 30235257
TI  - No evidence for morphometric associations of the amygdala and hippocampus with
      the five-factor model personality traits in relatively healthy young adults.
AB  - Despite the important functional role of the amygdala and hippocampus in
      socioemotional functioning, there have been limited adequately powered studies
      testing how the structure of these regions relates to putatively relevant
      personality traits such as neuroticism. Additionally, recent advances in MRI
      analysis methods provide unprecedented accuracy in measuring these structures and
      enable segmentation into their substructures. Using the new FreeSurfer amygdala
      and hippocampus segmentation pipelines with the full Human Connectome Project
      sample (N = 1105), the current study investigated whether the morphometry of
      these structures is associated with the five-factor model (FFM) personality
      traits in a sample of relatively healthy young adults. Drawing from prior
      findings, the following hypotheses were tested: 1) amygdala and hippocampus gray
      matter volume would be associated with neuroticism, 2) CA2/3 and dentate gyrus
      would account for the relationship of the hippocampus with neuroticism, and 3)
      amygdala gray matter volume would be inversely associated with extraversion.
      Exploratory analyses were conducted investigating potential associations between
      all of the FFM traits and the structure of the hippocampus and amygdala and their
      subregions. Despite some previous positive findings of whole amygdala and
      hippocampus with personality traits and related psychopathology (e.g.,
      depression), the current results indicated no relationships between the any of
      the brain regions and the FFM personality traits. Given the large sample and
      utilization of sophisticated analytic methodology, the current study suggests no
      association of amygdala and hippocampus morphometry with major domains of
      personality.

PMID- 30235258
TI  - Urban-rural difference in the associations between living arrangements and the
      health-related quality of life (HRQOL) of the elderly in China-Evidence from
      Shaanxi province.
AB  - BACKGROUND: So far limited evidence exist comparing the difference between urban
      and rural elder residents in relation to how living arrangements correlates to
      health-related quality of life(HRQOL) of the elderly. OBJECTIVE: This study aims
      to compare the HRQOL of the elderly with four living arrangements: living with
      spouse only (LS), living alone (LA), living with a spouse and adult children(LSC)
      and the single elderly living with adult children (SLC) in urban and rural areas
      of China. METHODS: The data were drawn from the 2013 wave of Chinese National
      Health Service Survey in Shaanxi Province, which included 11,729 elderly people.
      The Chinese version of the EQ-5D-3L questionnaire was used to measure the HRQOL.
      Tobit regression model and logistic regression models were employed to estimate
      the associations between living arrangements and the HRQOL of the elderly.
      RESULTS: The EQ-5D utility scores of the urban elderly with four different living
      arrangements (LS, LA,LSC and SLC) were 0.9141, 0.8392, 0.8176 and 0.9080, which
      were almost all higher than their rural counterparts. After controlling other
      confounding variables, tobit regression estimates showed that the EQ-5D utility
      scores of the single elderly either living alone or living with adult children
      were lower than the elderly living with a spouse in urban areas. In rural areas
      only the single elderly living with adult children were more disadvantaged.
      Additionally the logistic regression results showed living-alone elderly had
      worse psychological health and the single elderly living with adult children had
      worse physical health. CONCLUSION: The findings suggest that the urban elderly
      have better HRQOL than the rural elderly and the elderly with different living
      arrangements in urban and rural area have different HRQOL. More attention should
      be given to the poor mental health of the elderly living alone and the worse
      physical health of the single elderly living with adult children.

PMID- 30235259
TI  - Cytological characterization and molecular mapping of a novel recessive genic
      male sterility in sesame (Sesamum indicum L.).
AB  - Recessive genic male sterility (RGMS) has great potential for F1 hybrid seeds
      production in sesame (Sesamum indicum L.). However, it is not yet widely used in
      practice due to poor understanding of the underlying mechanism in RGMS.
      Previously, we have developed a novel sesame RGMS line (D248A) controlled by a
      single recessive gene. To elucidate its cytological mechanism, histological
      observations were carried out in sterile and fertile buds. The results indicated
      that abnormality in D248A began at microspore mother cell stage and persisted
      until microspore stage. The microsporocytes had less cytoplasm and no obvious
      nucleus. Normal meiosis failed in microspore mother cells. Cytoplasm condensation
      and vacuolation frequently occurred in tetrads, leading to the production of
      crumpled and abortive microspores. To develop molecular markers for breeding of
      hybrid lines, InDel and SSR markers were analyzed in a fertility segregating NIL
      population constructed by sib-mating D248A with D248B. Five markers were
      identified for the male sterile gene (Ms), with a respective genetic distance of
      1.47 and 5.17 cM for the two closest markers (SB2993 and LG1-170) on both sides.
      The Ms gene was further anchored into a 108-kb interval in the downstream of
      chromosome 1, within which 15 genes were predicted and four were likely to be
      responsible for male sterility. These findings provide a deeper understanding of
      the mechanism underlying RGMS in sesame.

PMID- 30235260
TI  - Sublethal effects of imidacloprid on the performance of the bird cherry-oat aphid
      Rhopalosiphum padi.
AB  - The bird cherry-oat aphid, Rhopalosiphum padi (L.), is a major insect pest of
      cereal crops in many countries. Imidacloprid has been widely used for controlling
      piercing-sucking insect pests worldwide, but its sublethal effects on R. padi
      have not been well addressed. In this study, we investigated the sublethal
      effects of imidacloprid on biological parameters and five enzyme activities of R.
      padi. The LC10, LC20, and LC25 of imidacloprid to adult aphids were 0.0053,
      0.0329 and 0.0659 mg L-1, respectively. These concentrations significantly
      decreased pre-adult survival rate, but prolonged the development duration of 1st
      instar nymphs, pre-oviposition period, and adult longevity. Adult oviposition
      period was also extended by LC20. The intrinsic rate of increase (r), net
      reproductive rate (R0), and finite rate (lambda) decreased at all three
      concentrations, whereas mean generation time (T) increased. Moreover, LC20 and
      LC25 significantly inhibited superoxide dismutase (SOD) activity, but increased
      catalase (CAT) activity. Acetylcholinesterase (AChE) activity also increased at
      LC20. However, cytochrome P450 enzyme and peroxidase (POD) activity did not
      differ between imidacloprid treatments and the control. In conclusion, the
      imidacloprid concentrations tested here have negative impacts on the performance
      of R. padi by reducing its nymphal survival, extending the development duration
      of some stages, decreasing the rate of population growth, and altering enzyme
      activities.

PMID- 30235261
TI  - Aquatic omnivores shift their trophic position towards increased plant
      consumption as plant stoichiometry becomes more similar to their body
      stoichiometry.
AB  - Human induced eutrophication has strongly altered aquatic ecosystems. With
      increasing eutrophication, plant nutrient concentrations increase, making them
      more attractive as food for herbivores. However, most aquatic consumers are
      omnivorous. Ecological stoichiometry theory predicts that animals prefer to
      consume food which has a similar nutrient (N and P) composition or C:nutrient
      ratio compared to their own bodies, hence omnivorous animals may prefer to eat
      animal prey instead of plants. We asked whether aquatic omnivores would shift
      their diet towards more plant consumption when plants are more nutritious and
      their stoichiometry becomes more similar to the stoichiometry of the omnivore. We
      hypothesized that: (1) the omnivore increases plant consumption as the plant
      C:nutrient ratio decreases when there is only plant material available; (2) the
      omnivore generally prefers animal food over plant material; (3) the omnivore will
      increase its relative plant consumption as the plant C:nutrient ratio decreases,
      in the presence of animal food. As a model system, we used the pond snail Lymnaea
      stagnalis (omnivorous consumer), the aquatic plant Potamogeton lucens (plant food
      to the consumer, cultured at different nutrient regimes to obtain different plant
      C:nutrient ratios), and the crustacean Gammarus pulex (animal food to the
      consumer, using freshly dead individuals). When there was only plant material
      available, the consumers increased their relative consumption rate with
      decreasing plant C:nutrient ratio from no measurable amount to about 102 mg g-1
      day-1. When plant material was offered simultaneously with animal food, even
      though the omnivores always preferred animal food over plant material, the
      omnivores still increased their relative intake of plant material as plant
      C:nutrient ratio decreased, from virtually nothing at the highest to on average
      16% of their diet at the lowest plant C:nutrient ratio, with a maximum of 28%.
      Therefore, we conclude that as nutrient loading increases in aquatic ecosystems,
      plant-eating omnivorous animals may shift their trophic position towards
      increased plant consumption and alter the food web structure. As a result, we may
      observe increased top-down control on aquatic plants.

PMID- 30235262
TI  - Using farmers' local knowledge of tree provision of ecosystem services to
      strengthen the emergence of coffee-agroforestry landscapes in southwest China.
AB  - Intensive monoculture coffee farms quickly expanded in Yunnan Province in the
      1990's and 2000's. In 2012, local authorities in Pu'er and Xishuangbanna
      Prefectures, the main coffee producing centre in the province, initiated a large
      scale conversion program of these farms towards coffee-agroforestry systems to
      promote "ecologically-friendly coffee". Shade tree inventories and household
      interviews were conducted in these two prefectures to characterize coffee farms
      and the Local Ecological Knowledge (LEK) of farmers on the provision of ecosystem
      services by associated tree species. This study on newly emerging coffee farming
      systems revealed a high level of tree species diversity at both farm and
      landscape levels despite the previous dominance of intensive coffee monoculture
      and the large-scale distribution of a limited number of shade tree species by the
      government. 162 tree species were encountered during farm inventories, out of
      which the community of coffee farmers was able to rank 30 against 9 ecosystem
      services and disservices. This study reveals that this LEK is a type of hybrid
      knowledge that still relies mostly on traditional knowledge of tree species
      combined with experience acquired from newly-implemented coffee-agroforestry
      practices. This study also pointed out knowledge gaps regarding the impact of
      mature trees on coffee yield, coffee quality and pest control. The participatory
      approach resulted in the identification of non-promoted species with a high
      potential to provide locally relevant ecosystem services in coffee-agroforestry
      systems. These results lead to the upgrade of an online tool
      (www.shadetreeadvice.org) which allows extension services generating lists of
      recommended shade tree species tailored to the local ecological context and
      individual farmers' needs. This tool will benefit farmers' livelihood, support
      landscape health and contribute to the sustainability of the emerging Yunnan
      coffee agriculture sector.

PMID- 30235263
TI  - Defense responses of lentil (Lens culinaris) genotypes carrying non-allelic
      ascochyta blight resistance genes to Ascochyta lentis infection.
AB  - Ascochyta blight of lentil is an important fungal disease in many lentil
      producing regions of the world causing major yield and grain quality losses.
      Quick shifts in aggressiveness of the population of the causal agent Ascochyta
      lentis mandates developing germplasm with novel and durable resistance. In the
      absence of complete resistance, lentil genotypes CDC Robin and 964a-46 have
      frequently been used as sources of partial resistance to ascochyta blight and
      carry non-allelic ascochyta blight resistance genes. RNA-seq analysis was
      conducted to identify differences in the transcriptome of CDC Robin, 964a-46 and
      the susceptible check Eston after inoculation with A. lentis. Candidate defense
      genes differentially expressed among the genotypes had hypothetical functions in
      various layers of plant defense, including pathogen recognition, phytohormone
      signaling pathways and downstream defense responses. CDC Robin and 964a-46
      activated cell surface receptors (e.g. receptor like kinases) tentatively
      associated with pathogen-associated molecular patterns (PAMP) recognition and
      nucleotide-binding site leucine-rich repeat (NBS-LRR) receptors associated with
      intracellular effector recognition upon A. lentis infection, and differed in
      their activation of salicylic acid, abscisic acid and jasmonic acid / ethylene
      signal transduction pathways. These differences were reflected in the
      differential expression of downstream defense responses such as pathogenesis
      related proteins, and genes associated with the induction of cell death and cell
      wall reinforcement. A significant correlation between expression levels of a
      selection of genes based on quantitative real-time PCR and their expression
      levels estimated through RNA-seq demonstrated the technical and analytical
      accuracy of RNA-seq for identification of genes differentially expressed among
      genotypes. The presence of different resistance mechanisms in 964a-46 and CDC
      Robin indicates their value for pyramiding gene leading to more durable
      resistance to ascochyta blight.

PMID- 30235264
TI  - Persistent metamorphopsia associated with branch retinal vein occlusion.
AB  - PURPOSE: To investigate longitudinal changes in metamorphopsia associated with
      branch retinal vein occlusion. METHODS: In this prospective observational case
      series, we included 32 eyes (32 patients) with branch retinal vein occlusion and
      acute macular edema. Eyes were treated as needed with intravitreal ranibizumab
      injections for 12 months. At baseline and 1, 6, and 12 months after initiating
      treatment, metamorphopsia was quantified using M-CHARTS. Retinal morphology was
      examined through optical coherence tomography. RESULTS: Logarithm of the minimum
      angle of resolution visual acuity progressively improved from 0.342 +/- 0.304
      (Snellen equivalent: 20/44) at baseline to 0.199 +/- 0.259 (20/32) and 0.118 +/-
      0.195 (20/26) at 1 and 12 months, respectively (both P < 0.001). The M-CHARTS
      score significantly decreased from 0.63 +/- 0.61 at baseline to 0.45 +/- 0.50 at
      1 month (P = 0.044), but no further improvement was achieved with 1 year of
      additional treatment (6 months: 0.47 +/- 0.53 [P = 0.094] and 12 months: 0.50 +/-
      0.44 [P = 0.173]). Three (13.6%) of 22 eyes with baseline metamorphopsia had
      complete metamorphopsia resolution. At 12 months, the M-CHARTS score was
      correlated with baseline foveal thickness (r = 0.373, P = 0.035) and the baseline
      M-CHARTS score (r = 0.503, P = 0.003). A multiple regression analysis revealed
      that only the baseline M-CHARTS score was correlated with the 12-month M-CHARTS
      score (beta = 0.460, P = 0.027). CONCLUSIONS: Eyes with branch retinal vein
      occlusion often have persistent metamorphopsia, even when visual acuity and
      retinal morphology improve. Metamorphopsia at 12 months was correlated with
      metamorphopsia and foveal thickness at baseline.

PMID- 30235265
TI  - Genetic associations and phenotypic heterogeneity in the craniosynostotic rabbit.
AB  - Craniosynostosis (CS) is a disorder that involves the premature ossification of
      one or more cranial sutures. Our research team has described a naturally
      occurring rabbit model of CS with a variable phenotype and unknown etiology.
      Restriction-site associated DNA (RAD) sequencing is a genomic sampling method for
      identifying genetic variants in species with little or no existing sequence data.
      RAD sequencing data was analyzed using a mixed linear model to identify single
      nucleotide polymorphisms (SNPs) associated with disease occurrence and onset in
      the rabbit model of CS. SNPs achieving a genome-wide significance of p <= 5 x 10
      8 were identified on chromosome 2 in association with disease occurrence and on
      chromosomes 14 and 19 in association with disease onset. Genotyping identified a
      coding variant in fibroblast growth factor binding protein 1 (FGFBP-1) on
      chromosome 2 and a non-coding variant upstream of integrin alpha 3 (ITGA3) on
      chromosome 19 that associated with disease occurrence and onset, respectively.
      Retrospective analysis of patient data revealed a significant inverse correlation
      between FGFBP-1 and ITGA3 transcript levels in patients with coronal CS. FGFBP-1
      and ITGA3 are genes with roles in early development that warrant functional study
      to further understand suture biology.

PMID- 30235267
TI  - Artificial reservoirs complement natural ponds to improve pondscape resilience in
      conservation corridors in a biodiversity hotspot.
AB  - Natural ponds are rich in biodiversity, contributing greatly to regional aquatic
      biodiversity. Artificial reservoirs used for irrigation can be significant
      additional features of the landscape. They infill the local natural pondscape,
      and are attractors for aquatic insects. Here, we determine the extent to which
      artificial reservoirs represent the local natural pond biota, and how they
      contribute to the pondscape in conservation corridors used to mitigate the impact
      of plantation forestry in a global biodiversity hotspot. We did this by: 1)
      identifying the environmental factors, including plants, that drive dragonfly,
      water beetle, and water bug species richness, diversity and composition, and 2)
      determining the value of natural ponds vs. artificial reservoirs for maintaining
      the population size and expanding the area of occupancy for dragonflies, beetles
      and bugs in conservation corridors. While vegetation cover was central for
      maintaining species richness and composition of the assemblages in general, many
      other environmental variables are necessary to encourage the full suite of local
      diversity. Artificial reservoirs are attractive habitats to many species, overall
      increasing area of occupancy for 75% of them (ranging from 62-84% for different
      taxa). These reservoirs provide complementary alternative habitats to natural
      ponds, leading to improved ecological resilience across the pondscape. We
      conclude that maintaining a diverse and heterogeneous pondscape is important for
      conserving local aquatic insect diversity, and that artificial reservoirs
      increase the local area of occupancy for a range of pond insects in conservation
      corridors, and improve the biodiversity value of these pondscapes.

PMID- 30235266
TI  - A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic
      fibrosis in dogs.
AB  - Ciliopathies presenting as inherited hepatorenal fibrocystic disorders are rare
      in humans and in dogs. We describe here a novel lethal ciliopathy in Norwich
      Terrier puppies that was diagnosed at necropsy and characterized as diffuse
      cystic renal disease and hepatic fibrosis. The histopathological findings were
      typical for cystic renal dysplasia in which the cysts were located in the
      straight portion of the proximal tubule, and thin descending and ascending limbs
      of Henle's loop. The pedigree of the affected puppies was suggestive of an
      autosomal recessive inheritance and therefore, whole exome sequencing and
      homozygosity mapping were used for identification of the causative variant. The
      analyses revealed a case-specific homozygous splice donor site variant in a cilia
      related gene, INPP5E: c.1572+5G>A. Association of the variant with the defect was
      validated in a large cohort of Norwich Terriers with 3 cases and 480 controls,
      the carrier frequency being 6%. We observed that the identified variant
      introduces a novel splice site in INPP5E causing a frameshift and formation of a
      premature stop codon. In conclusion, our results suggest that the INPP5E:
      c.1572+5G>A variant is causal for the ciliopathy in Norwich Terriers. Therefore,
      genetic testing can be carried out in the future for the eradication of the
      disease from the breed.

PMID- 30235268
TI  - Patterns of entropy production in dissolving natural porous media with flowing
      fluid.
AB  - The tendency for irreversible processes to generate entropy is the ultimate
      driving force for structure evolution in nature. In engineering, entropy
      production is often used as an indicator for loss of usable energy. In this
      study, we show that the analysis of entropy production patterns can provide
      insight into the diverse observations from experiments that investigate porous
      medium dissolution in imposed flow field. We first present a numerical scheme for
      the analysis of entropy production in dissolving porous media. Our scheme uses a
      greyscale digital model for chalk (an extremely fine grained rock), that was
      obtained using X-ray nanotomography. Greyscale models preserve structural
      heterogeneities with very high fidelity. We focussed on the coupling between two
      types of entropy production: the percolative entropy, generated by dissipating
      the kinetic energy of fluid flow, and the reactive entropy, originating from the
      consumption of chemical free energy. Their temporal patterns pinpoint three
      stages of microstructural evolution. We then showed that local mixing
      deteriorates fluid channelisation by reducing local variations of reactant
      concentration. We also showed that microstructural evolution can be sensitive to
      the initial transport heterogeneities, when the macroscopic flowrate is low. This
      dependence on flowrate indicates the need to resolve the structural features of a
      porous system when fluid residence time is long.

PMID- 30235269
TI  - Maternal genetic features of the Iron Age Tagar population from Southern Siberia
      (1st millennium BC).
AB  - Early nomads in the Eurasian steppes since the beginning of the 1st millennium BC
      played a key role in the formation of the cultural and genetic landscape of
      populations of a significant part of Eurasia, from Eastern Europe to Eastern
      Central Asia. Numerous archaeological cultures associated with early nomads have
      been discovered throughout the Eurasian steppe belt. The Tagar archaeological
      culture existed in the Minusinsk basin (Sayan Mountains, Southern Siberia,
      Russia) in the northeastern periphery of the Eurasian steppe belt from the 8th to
      1st century BC during the pre-Scythian, Scythian, and Early Xiongnu-Sarmatian
      periods. In this study, we evaluated mtDNA diversity in the Tagar population
      based on representative series (N = 79) belonging to all chronological stages of
      the culture. The Tagar population had a mixed mtDNA pool dominated by Western
      Eurasian haplogroups and subgroups (H, HV6, HV*, I, K, T, U2e, U4, U5a, and U*)
      and, to a lesser degree, Eastern Eurasian haplogroups (A*, A8, C*, C5, D, G2a,
      and F1b). The Tagar population showed a similar mtDNA pool structure to those of
      other Iron Age populations representing the "Scythian World." We observed
      particularly high similarity between the Tagar and Classic Scythians from the
      North Pontic region. Our results support the assumption that genetic components
      introduced by Bronze Age migrants from Western Eurasia contributed to the
      formation of the genetic composition of Scythian period populations in Southern
      Siberia. Another important component of the Tagar mtDNA pool was autochthonous
      East Eurasian lineages, some of which (A8 and C4a2a) are potential markers of the
      westward genetic influence of the eastern populations of the Scythian period. Our
      results suggest a genetic continuity (at least partial) between the Early,
      Middle, and Late Tagar populations.

PMID- 30235270
TI  - Relationships between borders, management agencies, and the likelihood of
      watershed impairment.
AB  - In the United States, the Clean Water Act (CWA) establishes water quality
      standards important for maintaining healthy freshwater ecosystems. Within the CWA
      framework, states define their own water quality criteria, leading to a potential
      fragmentation of standards between states. This fragmentation can influence the
      management of shared water resources and produce spillover effects of pollutants
      crossing state lines and other political boundaries. We used numerical
      simulations to test the null prediction of no difference in impairment between
      watersheds that cross political boundaries (i.e. state lines, national or coastal
      borders, hereafter termed "transboundary") and watersheds that cross no
      boundaries (hereafter "internal"). We found that transboundary watersheds are
      more likely to be impaired than internal watersheds. Further, we examined
      possible causes for this relationship based on both geographic and sociopolitical
      drivers. Though geographic variables such as human-modified land cover and the
      amount of upstream catchment area are associated with watershed impairment, the
      number and type of agencies managing land within a watershed better explained the
      different impairment levels between transboundary and internal watersheds.
      Watersheds primarily consisting of public lands are less impaired than watersheds
      consisting of private lands. Similarly, watersheds primarily managed by federal
      agencies are less impaired than state-managed watersheds. Our results highlight
      the importance of considering Integrated Watershed Management strategies for
      water resources within a fragmented policy framework.

PMID- 30235271
TI  - Brain metabolic and functional alterations in a liver-specific PTEN knockout
      mouse model.
AB  - Insulin resistance-as observed in aging, diabetes, obesity, and other
      pathophysiological situations, affects brain function, for insulin signaling is
      responsible for neuronal glucose transport and control of energy homeostasis and
      is involved in the regulation of neuronal growth and synaptic plasticity. This
      study investigates brain metabolism and function in a liver-specific Phosphatase
      and Tensin Homologue (Pten) knockout mouse model (Liver-PtenKO), a negative
      regulator of insulin signaling. The Liver-PtenKO mouse model showed an increased
      flux of glucose into the liver-thus resulting in an overall hypoglycemic and
      hypoinsulinemic state-and significantly lower hepatic production of the ketone
      body beta-hydroxybutyrate (as compared with age-matched control mice). The Liver
      PtenKO mice exhibited increased brain glucose uptake, improved rate of glycolysis
      and flux of metabolites in the TCA cycle, and improved synaptic plasticity in the
      hippocampus. Brain slices from both control- and Liver-PtenKO mice responded to
      the addition of insulin (in terms of pAKT/AKT levels), thereby neglecting an
      insulin resistance scenario. This study underscores the significance of insulin
      signaling in brain bioenergetics and function and helps recognize deficits in
      diseases associated with insulin resistance.

PMID- 30235273
TI  - The Extreme Climate Event Database (EXCEED): Development of a picture database
      composed of drought and flood stimuli.
AB  - The present study introduces the Extreme Climate Event Database (EXCEED), a
      picture database intended to induce emotionally salient stimuli reactions in the
      context of natural hazards associated with global climate change and related
      extreme events. The creation of the database was motivated by the need to better
      understand the impact that the increase in natural disasters worldwide has on
      human emotional reactions. This new database consists of 150 pictures divided
      into three categories: two negative categories that depict images of floods and
      droughts, and a neutral category composed of inanimate objects. Affective ratings
      were obtained using online survey software from 50 healthy Brazilian volunteers
      who rated the pictures according to valence and arousal, which are two
      fundamental dimensions used to describe emotional experiences. Valence refers to
      the appraisal of pleasantness conveyed by a stimulus, and arousal involves
      internal emotional activation induced by a stimulus. Data from picture rating,
      sex difference in affective ratings and psychometric properties of the database
      are presented here. Together, the data validate the use of EXCEED in research
      related to natural hazards and human reactions.

PMID- 30235272
TI  - Serial testing of healthcare workers for latent tuberculosis infection and long
      term follow up for development of active tuberculosis.
AB  - BACKGROUND: Healthcare workers (HCWs) are at high risk of tuberculosis (TB)
      infection due to occupational exposure. It is important to diagnose TB infections
      in HCWs to prevent nosocomial transmission, particularly among immunocompromised
      patients. OBJECTIVE: The aim of this study was to analyze the rate of tuberculin
      skin test (TST) conversion and to assess the incidence of active TB after the
      latent TB infection screenings in high-risk HCWs. METHODS: This retrospective
      cohort study involved 458 HCWs in TB-related departments between 2009 and 2013.
      All HCWs underwent a TST and a chest radiograph annually; an interferon-gamma
      release assay (IGRA) was performed on the TST-converted subjects. TST-converted
      and IGRA-positive HCWs underwent treatment for latent TB infection. RESULTS: The
      TST conversion rate was 30.3% from 2009 to 2011 in two years, 7.4% from 2011 to
      2012, and 17.4% from 2012 to 2013. Eleven subjects out of 42 TST converters (26%)
      were IGRA-positive; two of them developed into active pulmonary TB during the
      follow-up period. CONCLUSIONS: There was significant discordance between TST
      conversion and IGRA results in high-risk HCWs, and active TB developed only in
      TST-converted and IGRA-positive HCWs. Therefore, the combined use of TST and IGRA
      for periodic monitoring of TB infections in high-risk HCWs may be useful.

PMID- 30235274
TI  - Control and elimination of rabies in Croatia.
AB  - Despite the implementation of control measures (preventive dog vaccination),
      rabies has become endemic in Croatia, with red foxes being the main reservoir
      species. Oral rabies vaccination (ORV) campaigns supported by the European
      Commission have been conducted twice a year since the spring of 2011. The first
      campaigns were limited to the northern and eastern parts of the country, and from
      the autumn of 2012, the program was extended to the entire country. The Lysvulpen
      vaccine containing the SAD Bern strain was used for ORV. Following the
      vaccination campaigns, the number of rabies cases decreased, and the last
      positive case was recorded in February 2014. The bait uptake ranged from 24.86%
      to 84.62% and the immunisation rate from 11.24% to 35.64%.

PMID- 30235275
TI  - Influence of high-temperature exposure on the mating, oviposition and thermotaxis
      of Bactrocera cucurbitae (Coquillet) (Diptera:Tephritidae).
AB  - BACKGROUND: Bactrocera cucurbitae (Coquillett) is an important pest of cucurbit
      crops and certain vegetables in Asia, the Middle East, Africa and Hawaii. Most
      studies on B. cucurbitae have focussed on the effects of prolonged high
      temperature and very few have examined the effects of short-term exposures to
      high-temperature on behaviour. RESULTS: In this study, short-term of high
      temperature treatments of 33 degrees C, 37 degrees C, 41 degrees C and 45 degrees
      C were maintained for 1-3hr, and long-term, variable high-temperature treatments
      were established that consisted of experienced one, two and three times high
      temperatures stages to 31 degrees C, 33 degrees C, 34 degrees C, 35 degrees C, 36
      degrees C, 37 degrees C, 41 degrees C and 45 degrees C for 7hr. We compared the
      effects of the different high temperatures regimes changes treatments on the
      mating, oviposition and thermotactic taxis of the flies. The results showed that
      exposure to a 45 degrees C/1hr treatment, delayed both initiation of mating and
      oviposition for 8 hr relative to the control but mating and was observed 41 times
      and oviposition 47 times. By comparison, in the control, mating commenced
      immediately and was observed 38.3 times and oviposition was observed 41.3 times.
      Under the other treatments, all the indices for the flies declined with the
      increase in temperature and duration of exposure. CONCLUSION: Results showed that
      1hr of exposure to 45 degrees C significantly stimulated mating, oviposition and
      thermotactic behaviour of the flies. These results could improve our
      understanding of the mechanisms responsible for the population dynamics of B.
      cucurbitae during the high-temperature season.

PMID- 30235276
TI  - S100A12 facilitates osteoclast differentiation from human monocytes.
AB  - Osteoclasts play a critical role not only in bone homeostasis but also in
      inflammatory osteolysis, such as that occurring in inflammatory arthritis and
      systemic inflammation. In both inflammation conditions, inflammatory cytokines
      like Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha induce RANKL
      expression in osteoblasts, but the roles of these cytokines in osteoclast
      activation remain unclear. S100A12, an S100 family member, is a low-molecular
      weight calcium-binding protein. Although it has a pro-inflammatory role, its
      effects on osteoclast differentiation have been unclear. Here we examined the
      direct effects of S100A12 on human osteoclasts in vitro. S100A12 facilitated
      osteoclast formation in the presence of RANKL, as judged by the cells' morphology
      and elevated expression of osteoclast-related molecules, including NFATc1, ACP5,
      CALCR, and ITGbeta3. In addition, S100A12 administration markedly enhanced the
      osteoclasts' bone resorption ability, consistent with their increased expression
      levels of CTSK and CA2. Blocking RAGE and TLR4 cancelled the effects of S100A12.
      Our results indicate that S100A12 is a potential therapeutic target for
      inflammatory osteolysis.

PMID- 30235277
TI  - Decreased nitrite reductase activity of deoxyhemoglobin correlates with platelet
      activation in hemoglobin E/beta-thalassemia subjects.
AB  - Nitric oxide (NO) can be generated from nitrite by reductase activity of
      deoxygenated hemoglobin (deoxyHb) apparently to facilitate tissue perfusion under
      hypoxic condition. Although hemoglobin E (HbE) solutions have been shown to
      exhibit decreased rate of nitrite reduction to NO, this observation has never
      been reported in erythrocytes from subjects with hemoglobin E/beta-thalassemia
      (HbE/beta-thal). In this study, we investigated the nitrite reductase activity of
      deoxyHb dialysates from 58 non-splenectomized and 23 splenectomized HbE/beta-thal
      subjects compared to 47 age- and sex-matched normal subjects, and examined its
      correlation with platelet activity. Iron-nitrosyl-hemoglobin (HbNO) was measured
      by tri-iodide reductive chemiluminescence as a marker of NO generation. HbNO
      produced from the reaction of nitrite with deoxyHb dialysate from both non
      splenectomized and splenectomized HbE/beta-thal subjects was lower than that of
      normal (AA) hemoglobin subjects. P-selectin expression, a marker of platelet
      activation, at baseline and in reactivity to stimulation by adenosine diphosphate
      (ADP), were higher in HbE/beta-thal subjects than normal subjects. HbNO formation
      from the reactions of nitrite and deoxyHb inversely correlated with baseline
      platelet P-selectin expression, HbE levels, and tricuspid regurgitant velocity
      (TRV). Nitrite plus deoxygenated erythrocytes from HbE/beta-thal subjects had a
      lower ability to inhibit ADP-induced P-selectin expression on platelets than
      erythrocytes from normal subjects. We conclude that deoxyHb in erythrocytes from
      HbE/beta-thal subjects has a decreased ability to reduce nitrite to NO, which is
      correlated with increased platelet activity in these individuals.

PMID- 30235278
TI  - Inhibition and counterinhibition of Surfacen, a clinical lung surfactant of
      natural origin.
AB  - Inactivation of pulmonary surfactant by different components such as serum,
      cholesterol or meconium contributes to severe respiratory pathologies through
      destabilization and collapse of airspaces. Recent studies have analyzed in detail
      how the interfacial properties of natural surfactant purified from animal lungs
      are altered as a consequence of its exposure to serum proteins or meconium
      mobilized cholesterol. It has been also demonstrated that pre-exposure of
      surfactant to polymers such as hyaluronic acid provides resistance to
      inactivation by multiple inhibitory agents. In the current work, we have extended
      these studies to the analysis of Surfacen, a clinical surfactant currently in use
      to rescue premature babies suffering or at risk of respiratory distress due to
      congenital lack of surfactant. This surfactant is also strongly inhibited by both
      meconium and serum when tested in the captive bubble surfactometer (CBS) under
      conditions mimicking respiratory dynamics. As it occurs with native surfactant,
      Surfacen is markedly protected from inhibition by pre-exposure to hyaluronic
      acid, confirming that clinical surfactants can be improved to treat pathologies
      associated with strongly deactivating contexts, such as those associated with
      lung injury and inflammation. Remarkably, we found that, under physiologically
      mimicking conditions, a cholesterol-free clinical surfactant such as Surfacen is
      less susceptible to inhibition by cholesterol-mobilizing environments than
      cholesterol-containing natural surfactant, as a consequence of a markedly reduced
      susceptibility to incorporation of exogenous cholesterol.

PMID- 30235280
TI  - Genetic variants analysis of three dromedary camels using whole genome sequencing
      data.
AB  - Whole genome wide identification and annotation of genetic variations in camels
      is in its first steps. The aim of this study was the identification of genome
      wide variants, functional annotations of them and enrichment analysis of affected
      genes using whole genome sequencing data of three dromedary camels. The genomes
      of two Iranian female dromedary camels that mostly used to produce meat and milk
      were sequenced to 41.9-fold and 38.6-fold coverage. A total of 4,727,238 single
      nucleotide polymorphisms (SNPs) and 692,908 indels (insertions and deletions)
      were found by mapping raw reads to the dromedary reference assembly (GenBank
      Accession: GCA_000767585.1). In-silico functional annotation of the discovered
      variants in under study samples revealed that most SNPs (2,305,738; 48.78%) and
      indels (339,756; 49.03%) were located in intergenic regions. A comparison of the
      identified SNPs with those of the African camel (BioProject Accession:
      PRJNA269274) indicated that they had 993,474 SNPs in common. We found 15,168 non
      synonymous SNPs in the shared variants of the three camels that could affect gene
      function and protein structure. Obtained results revealed that there were 7085,
      6271 and 4688 non-synonymous SNPs among the 3436, 3058 and 2882 genes in the
      specific gene sets of Yazd dromedary, Trod dromedary and African dromedary,
      respectively. The list of genes predicted to be affected by non-synonymous
      variants in different individuals was subjected to gene ontology (GO) enrichment
      analysis.

PMID- 30235281
TI  - Early CD8+-recovery independently predicts low probability of disease relapse but
      also associates with severe GVHD after allogeneic HSCT.
AB  - In this single-center study we retrospectively evaluated the impact of early
      reconstitution of different lymphocyte subsets on patient outcomes after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). We found that
      CD8+ T-cell counts exceeding 50x106/l as early as on day 28 post-transplantation
      correlated significantly with decreased relapse risk, with three-year relapse
      rates of 17.0% and 55.6% (P = 0.002), but were also associated with severe acute
      and chronic GVHD. Incidence of grade III-IV acute GVHD was 30.5% for those with
      early CD8+ T-cell recovery compared to 2.1% for those with lower CD8+ T-cell
      counts on day 28 post-transplant (HR = 20.24, P = 0.004). Early CD8+ T-cell
      reconstitution did not, however, affect the overall survival. Multivariate
      analysis showed that slow CD8+ T-cell reconstitution was strongly associated with
      increased risk of relapse (HR = 3.44, P = 0.026). A weaker correlation was found
      between CD4+ reconstitution and relapse-risk, but there was no such association
      with CD19+ B-cells or NK-cells. In conclusion, the early CD8+ T-cell recovery on
      day 28 post-transplant is associated with the lower risk of relapse but also
      predicts the impending severe GVHD, and thus could be useful in guiding timely
      treatment decisions.

PMID- 30235279
TI  - Propionate-producing bacteria in the intestine may associate with skewed
      responses of IL10-producing regulatory T cells in patients with relapsing
      polychondritis.
AB  - Relapsing polychondritis (RP) is an inflammatory disease of unknown causes,
      characterized by recurrent inflammation in cartilaginous tissues of the whole
      body. Recently, researchers have reported that, in mouse experiments, altered gut
      microbe-dependent T cell differentiation occurred in gut associated lymphoid
      tissues. Here, we investigated whether gut microbe alteration existed, and if so,
      the alteration affected peripheral T cell differentiation in patients with RP. In
      an analysis of gut microbiota, we found increased annotated species numbers in RP
      patients compared with normal individuals. In the RP gut microbiota, we observed
      several predominant species, namely Veillonella parvula, Bacteroides eggerthii,
      Bacteroides fragilis, Ruminococcus bromii, and Eubacterium dolichum, all species
      of which were reported to associate with propionate production in human
      intestine. Propionate is a short-chain fatty acid and is suggested to associate
      with interleukin (IL)10-producing regulatory T (Treg) cell differentiation in gut
      associated lymphoid tissues. IL10 gene expressions were moderately higher in
      freshly isolated peripheral blood mononuclear cells (PBMC) of RP patients than
      those of normal individuals. Six hours after the initiation of the cell culture,
      regardless of the presence and absence of mitogen stimulation, IL10 gene
      expressions were significantly lower in RP patients than those in normal
      individuals. It is well known that PBMC of patients with autoimmune and
      inflammatory diseases show hyporesponsiveness to mitogen stimulation. We suggest
      that, in RP patients, continuous stimulation of intestinal T cells by excessive
      propionate leads to the spontaneous IL10 production and a subsequent refractory
      period of T cells in patients with RP. The hyporesponsiveness of Treg cells upon
      activation may associate with inflammatory cytokine production of PBMC and
      subsequently relate to chondritis in RP patients.

PMID- 30235282
TI  - Association of socioeconomic status and health-related behavior with elderly
      health in China.
AB  - Previous health studies have focused on the correlation between socioeconomic
      status (SES) and health. We pooled data from the Chinese Longitudinal Healthy
      Longevity Survey (N = 9765) conducted in 2011, and examined the association of
      SES and health-related behavior with elderly health in China. The cumulative
      health disadvantage of the elderly caused by SES can be relieved by lifelong
      health-related behavior. In the same SES, the odds of self-rated health (SRH) as
      "good," mini-mental state examination (MMSE) as "not impaired," and activities of
      daily living (ADLs) as "not impaired" among the elderly who exercised regularly,
      were 46.9%, 28.6%, and 62.3% lower for the elderly who rarely exercised. The
      elderly who started doing regular exercise from 30 years old, achieved higher
      SRH, ADL, and MMSE scores to some extent. The health improvement advantage for
      the elderly who started doing regular exercises after 60 years old, was reduced.
      However, the odds of SRH as "good," MMSE as "not impaired," and ADLs as "not
      impaired" were still 3.4%, 12.5%, and 17.8%, respectively, higher than the
      respondents who never exercised. The health-related behaviors not only promote
      elderly health improvement, but its duration has also been found to be associated
      with the extent of health improvement.

PMID- 30235283
TI  - Comparing medical, dental, and nursing students' preparedness to address lesbian,
      gay, bisexual, transgender, and queer health.
AB  - BACKGROUND: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) populations
      face multiple health disparities including barriers to healthcare. Few studies
      have examined healthcare trainees' perceptions of their preparedness to care for
      LGBTQ populations and none have compared perceptions of training across medicine,
      dental medicine, and nursing. We aimed to understand variations across
      disciplines in LGBTQ health by assessing medical, dental, and nursing students'
      perceptions of preparedness across three domains: comfort levels, attitudes, and
      formal training. METHODS: We developed a 12-item survey with an interprofessional
      panel of LGBTQ students from the schools of medicine, dental medicine, and
      nursing at a top-tier private university in the United States. Any student
      enrolled full time in any of the three schools were eligible to respond. We
      performed descriptive statistical analyses and examined patterns in responses
      using Kruskal-Wallis tests and an ordered logistic regression model. RESULTS:
      1,010 students from the Schools of Medicine, Dental Medicine, and Nursing
      responded to the survey for an overall response rate of 43%. While 70-74% of all
      student respondents felt comfortable treating LGBTQ patients, fewer than 50%
      agreed that their formal training had prepared them to do so. Overall, 71-81% of
      students reported interest in receiving formal LGBTQ health education, though
      dental students were significantly less likely than medical students to report
      this interest (OR 0.53, p<0.01). Respondents who identified as LGBQ were
      significantly less likely than heterosexual students to agree that training was
      effective (OR 0.55, p<0.01) and that their instructors were competent in LGBTQ
      health (OR 0.56, p<0.01). CONCLUSION: Despite high comfort levels and positive
      attitudes towards LGBTQ health, most student respondents did not report adequate
      formal preparation. There were some significant differences between disciplines,
      but significant gaps in training exist across disciplines. Health professional
      schools should develop formal content on LGBTQ health and utilize this content as
      an opportunity for interprofessional training.

PMID- 30235285
TI  - Nanoscale imaging of the adhesion core including integrin beta1 on intact living
      cells using scanning electron-assisted dielectric-impedance microscopy.
AB  - The integrins are a superfamily of transmembrane proteins composed of alpha and
      beta subunit dimers involved in cell-cell and cell-extracellular matrix
      interactions. The largest integrin subgroup is integrin beta1, which contributes
      to several malignant phenotypes. Recently, we have developed a novel imaging
      technology named scanning electron-assisted dielectric-impedance microscopy (SE
      ADM), which visualizes untreated living mammalian cells in aqueous conditions
      with high contrast. Using the SE-ADM system, we observed 60-nm gold colloids with
      antibodies directly binding to the focal adhesion core containing integrin beta1
      on mammalian cancer cells without staining and fixation. The adhesion core
      contains three or four high-density regions of integrin beta1 and connects to the
      actin filament. An adhesion core with high-density integrin beta1 is suggested to
      contain 10-20 integrin dimers. Our SE-ADM system can also visualize various other
      membrane proteins in living cells in medium without staining and fixation.

PMID- 30235287
TI  - Air movement sound production by alewife, white sucker, and four salmonid fishes
      suggests the phenomenon is widespread among freshwater fishes.
AB  - We sought to describe sounds of some of the common fishes suspected of producing
      unidentified air movement sounds in soundscape surveys of freshwater habitats in
      the New England region of North America. Soniferous behavior of target fishes was
      monitored in real time in the field in both natural and semi-natural environments
      by coupling Passive Acoustic Monitoring (PAM) with direct visual observation from
      shore and underwater video recording. Sounds produced by five species including,
      alewife (Alosa pseudoharengus, Clupeidae), white sucker (Catastomus commersonii,
      Catostomidae), brook trout (Salvelinus fontinalis, Salmonidae), brown trout
      (Salmo trutta, Salmonidae), and rainbow trout (Oncorhynchus mykiss, Salmonidae)
      were validated and described in detail for the first time. In addition, field
      recordings of sounds produced by an unidentified salmonid were provisionally
      attributed to Atlantic salmon (Salmo salar, Salmonidae). Sounds produced by all
      species are of the air movement type and appear to be species specific. Our data
      based on fishes in three distinct orders suggest the phenomenon may be more
      ecologically important than previously thought. Even if entirely incidental, air
      movement sounds appear to be uniquely identifiable to species and, hence, hold
      promise for PAM applications in freshwater and marine habitats.

PMID- 30235284
TI  - Lrp4/Wise regulates palatal rugae development through Turing-type reaction
      diffusion mechanisms.
AB  - Periodic patterning of iterative structures is diverse across the animal kingdom.
      Clarifying the molecular mechanisms involved in the formation of these structure
      helps to elucidate the process of organogenesis. Turing-type reaction-diffusion
      mechanisms have been shown to play a critical role in regulating periodic
      patterning in organogenesis. Palatal rugae are periodically patterned ridges
      situated on the hard palate of mammals. We have previously shown that the palatal
      rugae develop by a Turing-type reaction-diffusion mechanism, which is reliant
      upon Shh (as an inhibitor) and Fgf (as an activator) signaling for appropriate
      organization of these structures. The disturbance of Shh and Fgf signaling lead
      to disorganized palatal rugae. However, the mechanism itself is not fully
      understood. Here we found that Lrp4 (transmembrane protein) was expressed in a
      complementary pattern to Wise (a secreted BMP antagonist and Wnt modulator)
      expression in palatal rugae development, representing Lrp4 expression in
      developing rugae and Wise in the inter-rugal epithelium. Highly disorganized
      palatal rugae was observed in both Wise and Lrp4 mutant mice, and these mutants
      also showed the downregulation of Shh signaling, which was accompanied with
      upregulation of Fgf signaling. Wise and Lrp4 are thus likely to control palatal
      rugae development by regulating reaction-diffusion mechanisms through Shh and Fgf
      signaling. We also found that Bmp and Wnt signaling were partially involved in
      this mechanism.

PMID- 30235286
TI  - Safety and tolerability of HIV-1 multiantigen pDNA vaccine given with IL-12
      plasmid DNA via electroporation, boosted with a recombinant vesicular stomatitis
      virus HIV Gag vaccine in healthy volunteers in a randomized, controlled clinical
      trial.
AB  - BACKGROUND: The addition of plasmid cytokine adjuvants, electroporation, and live
      attenuated viral vectors may further optimize immune responses to DNA vaccines in
      heterologous prime-boost combinations. The objective of this study was to test
      the safety and tolerability of a novel prime-boost vaccine regimen incorporating
      these strategies with different doses of IL-12 plasmid DNA adjuvant. METHODS: In
      a phase 1 study, 88 participants received an HIV-1 multiantigen (gag/pol, env,
      nef/tat/vif) DNA vaccine (HIV-MAG, 3000 MUg) co-administered with IL-12 plasmid
      DNA adjuvant at 0, 250, 1000, or 1500 MUg (N = 22/group) given intramuscularly
      with electroporation (Ichor TriGridTM Delivery System device) at 0, 1 and 3
      months; followed by attenuated recombinant vesicular stomatitis virus, serotype
      Indiana, expressing HIV-1 Gag (VSV-Gag), 3.4 ? 107 plaque-forming units (PFU), at
      6 months; 12 others received placebo. Injections were in both deltoids at each
      timepoint. Participants were monitored for safety and tolerability for 15 months.
      RESULTS: The dose of IL-12 pDNA did not increase pain scores, reactogenicity, or
      adverse events with the co-administered DNA vaccine, or following the VSV-Gag
      boost. Injection site pain and reactogenicity were common with intramuscular
      injections with electroporation, but acceptable to most participants. VSV-Gag
      vaccine often caused systemic reactogenicity symptoms, including a viral syndrome
      (in 41%) of fever, chills, malaise/fatigue, myalgia, and headache; and decreased
      lymphocyte counts 1 day after vaccination. CONCLUSIONS: HIV-MAG DNA vaccine given
      by intramuscular injection with electroporation was safe at all doses of IL-12
      pDNA. The VSV-Gag vaccine at this dose was associated with fever and viral
      symptoms in some participants, but the vaccine regimens were safe and generally
      well-tolerated. TRIAL REGISTRATION: Clinical Trials.gov NCT01578889.

PMID- 30235288
TI  - Validation of a standardized MRI method for liver fat and T2* quantification.
AB  - PURPOSE: Several studies have demonstrated the accuracy, precision, and
      reproducibility of proton density fat fraction (PDFF) quantification using vendor
      specific image acquisition protocols and PDFF estimation methods. The purpose of
      this work is to validate a confounder-corrected, cross-vendor, cross field
      strength, in-house variant LMS IDEAL of the IDEAL method licensed from the
      University of Wisconsin, which has been developed for routine clinical use.
      METHODS: LMS IDEAL is implemented using a combination of patented and/or
      published acquisition and some novel model fitting methods required to correct
      confounds which result from the imaging and estimation processes, including:
      water-fat ambiguity; T2* relaxation; multi-peak fat modelling; main field
      inhomogeneity; T1 and noise bias; bipolar readout gradients; and eddy currents.
      LMS IDEAL has been designed to use image acquisition protocols that can be
      installed on most MRI scanners and cloud-based image processing to provide fast,
      standardized clinical results. Publicly available phantom data were used to
      validate LMS IDEAL PDFF calculations against results from originally published
      IDEAL methodology. LMS PDFF and T2* measurements were also compared with an
      independent technique in human volunteer data (n = 179) acquired as part of the
      UK Biobank study. RESULTS: We demonstrate excellent agreement of LMS IDEAL across
      vendors, field strengths, and over a wide range of PDFF and T2* values in the
      phantom study. The performance of LMS IDEAL was then assessed in vivo against
      widely accepted PDFF and T2* estimation methods (LMS Dixon and LMS T2*,
      respectively), demonstrating the robustness of LMS IDEAL to potential sources of
      error. CONCLUSION: The development and clinical validation of the LMS IDEAL
      algorithm as a chemical shift-encoded MRI method for PDFF and T2* estimation
      contributes towards robust, unbiased applications for quantification of hepatic
      steatosis and iron overload, which are key features of chronic liver disease.

PMID- 30235289
TI  - How do organisational configuration and context influence the quantity and
      quality of NHS services provided by English community pharmacies? A qualitative
      investigation.
AB  - Community pharmacies are expanding their role into medicines-related healthcare
      and public health services, previously the domain of physicians and nurses,
      driven by policies to improve healthcare access for patients and to address
      problems of increasing demands and rising costs in primary and urgent care
      services. Understanding the organisational context into which this expansion is
      taking place is necessary given concerns over the extent to which pharmacies
      prioritise service volume over the quality of service provision. As part of a
      larger programme of work, this paper aims to explore stakeholder perceptions of
      the organisational and extra-organisational factors associated with service
      quality and quantity in community pharmacy as an established exemplar of private
      sector organisations providing publicly-funded healthcare. With ethics committee
      approval, forty semi-structured interviews were conducted with service
      commissioners, superintendent and front-line pharmacists, purposively selected
      from across nine geographical areas and a range of community pharmacy
      organisational types in England. Interviews were audio-recorded, transcribed
      verbatim and thematically analysed. Findings highlight the perceived importance
      of appropriate staffing and skill-mix for promoting service quantity and quality
      in community pharmacy. Organisational cultures which supported team development
      were viewed as facilitatory whereas those prioritising business targets over
      service quality seen to be inhibitive. Older local populations and low patient
      expectations were thought to limit service uptake as was poor integration with
      wider primary care services. The contractual framework and commissioning
      processes were also seen as a barrier to increasing service quality, quantity and
      integration in this sector. These findings suggest that healthcare
      administrations should take account of organisational and extra-organisational
      drivers and barriers when commissioning services from private sector providers
      such as community pharmacies to ensure that the quality of service provision is
      incentivised in addition to service quantity. Additionally, collaborative working
      should be encouraged through integrated commissioning mechanisms.

PMID- 30235291
TI  - Are fishery management upgrades worth the cost?
AB  - Many analyses of fishery recovery have demonstrated the potential biological and
      economic benefits of management reform, but few have compared these to the
      associated costs of management upgrades, which can be substantial. This study
      aims to determine if the projected economic benefits of management reform
      outweigh the increases in management costs required to achieve those benefits. To
      answer this question, we developed a database of country-level fisheries
      management costs and use those to estimate the country-level costs of management
      changes. We use this framework to compare estimates of future costs of management
      upgrades against their economic benefits in terms of profit. Results indicate
      that for most nations, including the top 25 fishing nations, management upgrades
      outweigh their associated costs. This result is robust to a number of alternative
      assumptions about costs. Results also suggest that stronger reforms such as
      rights-based management, although sometimes more expensive to implement, can lead
      to greater net economic benefits compared to alternatives.

PMID- 30235290
TI  - Multi-informant path models of the influence of psychosocial and treatment
      related variables on adherence and metabolic control in adolescents with type 1
      diabetes mellitus.
AB  - BACKGROUND: We assessed the associations between metabolic control and adherence
      and a broad range of adolescent and family characteristics (e.g., gender, family
      structure), treatment-related variables (e.g., disease duration, treatment
      modality), and psychosocial factors (e.g., symptoms of depression and anxiety,
      parental support, self-efficacy) in a nationwide study of Danish adolescents (age
      12-17 years) with type 1 diabetes mellitus (T1DM). METHODS: Sixty-four percent of
      invited families participated by completing a survey and providing a blood
      sample. Two path models of associations between generic and diabetes-related
      family factors, adolescent self-efficacy, emotional difficulties, and metabolic
      control and adherence were tested, one for adolescents and one for caregivers.
      Demographic variables were included as covariates. RESULTS: Both path models
      demonstrated a satisfying model fit. In both models, metabolic control was
      associated with adherence, age, and T1DM duration. In the adolescent model,
      metabolic control was also related to treatment modality, single-parent
      household, caregiver non-support, and anxiety, whereas in the caregiver model
      metabolic control was associated with family conflict and caregiver support. In
      both models, adherence was related to age, duration, treatment modality, family
      conflict, caregiver support, family functioning, and emotional difficulties of
      the adolescent. In the adolescent model, adherence was also related to adolescent
      self-efficacy, whereas in the caregiver model adherence was associated with
      adolescent gender and caregiver non-support and support. Adolescent self
      efficacy, emotional well-being, and difficulties related to adolescent/caregiver
      interaction appeared to be particularly important, as indicated by their stronger
      association with adherence and/or metabolic control. CONCLUSION: The results
      highlight the value of applying a multi-informant approach to address the
      psychosocial well-being of adolescents with diabetes in a large national sample.
      Self-efficacy, emotional, and family-related difficulties are important aspects
      to address in both clinical care and future research regarding adolescents with
      T1DM.

PMID- 30235292
TI  - The efficacy and safety of targeted therapy plus fulvestrant in postmenopausal
      women with hormone-receptor positive advanced breast cancer: A meta-analysis of
      randomized-control trials.
AB  - OBJECTIVE: To evaluate the efficacy and safety of targeted therapy plus
      fulvestrant for postmenopausal patients with hormone receptor-positive advanced
      breast cancer. METHODS: Pubmed, Embase and Web of Science databases were
      systematically searched on February 26, 2018. Eligible studies were screened
      according to selection criteria, and two reviewers independently extracted
      outcome data which included progression-free survival, overall survival,
      objective response rate, clinical benefit rate and toxicities. RevMan 5.3 and
      STATA 11.0 software were used to conduct meta-analysis. RESULTS: Thirteen
      articles including twelve randomized-control trials fulfilled selection criteria.
      There was no evidence regarding the existence of publication bias and high-risk
      bias of quality in the selected studies. In previously endocrine therapy-treated
      postmenopausal patients with hormone-receptor positive advanced breast cancer,
      the PFS (HR = 0.77, 95%CI: 0.66-0.91) and ORR (RR = 1.78, 95%CI: 1.35-2.34) of
      combination therapy group were significantly higher than that from fulvestrant
      monotherapy group. Besides, a statistically significant difference in PFS was
      found across the two arms in postmenopausal women with PIK3CA-mutant ctDNA tumor
      (HR = 0.52, 95% CI: 0.39-0.69). Moreover, the risk of adverse events (RR = 1.09,
      95%CI: 1.05-1.13), CTCAE>=3 (RR = 1.97, 95%CI: 1.49-2.60) and discontinuation due
      to adverse events (RR = 4.91, 95%CI: 3.37-7.15) were also significantly different
      between two treatment groups. Sensitivity analysis showed PLOMA-3 trial was an
      important factor of heterogeneity. DISCUSSION: Even though the combination of
      targeted therapy plus fulvestrant improved PFS and increased ORR in advanced
      breast cancer patients, the toxicities of combination therapy were also higher
      than fulvestrant monotherapy. Further studies related to inhibitors targeting the
      specific signaling pathway or receptors are urgently needed, and more efforts
      concerning precision medicine of targeted therapy plus endocrine therapy should
      be taken to improve the clinical benefits.

PMID- 30235293
TI  - Cancer mortality attributable to cigarette smoking in 2005, 2010 and 2015 in
      Qingdao, China.
AB  - INTRODUCTION: Cigarette smoking is among the most important public health
      concerns worldwide and the leading preventable cause of illness and death
      associated with cancer, chronic obstructive pulmonary disease (COPD) and
      cardiovascular disease (CVD). Although Qingdao, China implemented smoking control
      measures in 2007 and smoke-free legislation in 2013, smoking-attributable cancer
      mortality remains at a high level. The present study aimed to facilitate changes
      in policy-making, intervention implementation, monitoring and evaluation by
      estimating and comparing the burden of smoking-attributable cancers in Qingdao
      during 2005, 2010 and 2015. METHODS: This study used the disease list from the
      Global Burden of Disease (GBD) study to quantify the burden of smoking-related
      cancer. Sex and age-specific smoking-attributable mortality data were collected
      from the Qingdao Municipal Center for Disease Control and Prevention using an
      online reporting system. The population-attributable fractions (PAFs) of smoking
      and smoking-attributable cancer mortality in 2005, 2010 and 2015 were estimated
      using the smoking impact ratio (SIR) and relative risks (RRs) and by multiplying
      the smoking-attributable fraction by total cancer mortality, respectively.
      RESULTS: The numbers of smoking-attributable cancer deaths increased from 2484 in
      2005 to 2999 in 2010 and 4148 in 2015, with corresponding PAFs of 26.41%, 25.76%
      and 29.13%, respectively. The PAFs were higher among men (vs. women) for all
      cancers except cervical cancer. In 2005, lung, liver, esophageal and stomach
      cancers were most frequently associated with smoking-associated cancer mortality,
      and lung cancer had the greatest PAF, followed by nasopharyngeal, oral and
      esophageal cancers. Similar patterns were observed in 2010 and 2015. In 2015, 1
      in 3 and 1 in 5 cancer deaths in men and women, respectively, were attributable
      to smoking, and 95% of these deaths were associated with lung, liver, esophageal
      or stomach cancer. Over time, downward and upward trends in smoking-attributable
      cancer deaths were respectively observed among people younger than and older than
      50 years. CONCLUSIONS: The smoking-attributable cancer burden in Qingdao remains
      considerable, despite the implementation of tobacco control and smoke-free
      measures. Tobacco control efforts should remain a major public health priority.

PMID- 30235295
TI  - Venous versus capillary sampling for total creatine kinase assay: Effects of a
      simulated football match.
AB  - BACKGROUND: Capillary rather than venipuncture may be a simpler and less invasive
      blood collection protocol that would increase the number of potential sampling
      tests. However, if capillary sampling can be used as an alternative to
      venipuncture to determine changes in plasma, total creatine kinase (CK) activity
      in response to a football training session is poorly known. OBJECTIVE: This study
      aims to determine whether capillary blood sampling would provide representative
      measures of total CK activity compared to venipuncture in response to a football
      training session-induced elevated CK plasma levels. METHODS: Twenty-two players
      from an under-19 football team performed a simulated football match with 11
      players on each team for 90 minutes total duration (two halves of 45 minutes with
      15 minutes rest between). Venous and ear lobe capillary blood samples were
      collected before and after (24h and 48h) the training session. Athletes retested
      for three consecutive days after exercise during the recovery week. RESULTS: The
      simulated match significantly increased (P< 0.05) total CK activity as determined
      in both venous (1.7-fold) and capillary (1.9-fold) blood sampling. Total CK
      activity determined using capillary samples demonstrated significant correlation
      (r = 0.85; P < 0.01) and an elevated concordance Lin index (pc = 0.80) when
      compared to venous sampling total CK. The Bland-Altman plot showed capillary
      sampling CK overestimated venous CK levels by 130 U/L (61%), with moderated
      variance and low bias. CONCLUSIONS: Our results demonstrated that capillary
      sampling for total CK activity assay may be considered a reliable alternative to
      venipuncture to determine changes in plasma total CK activity in response to a
      football training session.

PMID- 30235294
TI  - Association between stages of change for smoking cessation and electronic
      cigarette use among adult smokers: A nationwide cross-sectional study in Korea.
AB  - This study aimed to investigate whether smokers who are ready to quit are more
      likely to use electronic cigarette (e-cigarette) than those who are not. The
      association between the ever and current use of e-cigarettes with the stages of
      change (SOC) model was examined, which reflects the readiness to quit smoking.
      Current smokers were categorized based on the SOC (precontemplation,
      contemplation, and preparation). We investigated the associations between quit
      attempts, intention to quit, and stage of change with e-cigarette use in the
      general population and different age groups. We used data from the Korea
      Community Health Survey that was conducted nationwide in 2014, and 45,378 current
      smokers were included in the study. Adult smokers were more likely to use e
      cigarettes simultaneously in the preparation and contemplation stages than in the
      precontemplation stage (adjusted odds ratio [AOR] of preparation stage: 2.88 and
      95% confidence interval [CI]: 2.26-3.66; AOR of contemplation stage: 1.93 and 95%
      CI: 1.67-2.24). Ever use of e-cigarette was significantly associated with the
      contemplation stage in smokers younger than 50 years, while current e-cigarette
      use was greater in the contemplation stage than in the precontemplation stage at
      all ages. Both ever and current use of e-cigarettes were significantly related
      with the preparation stage among all age groups except 50-59 years. Because the
      use of e-cigarette among smokers may continually increase, public health guidance
      must be provided to different types of dual users. Previous studies on the
      association between e-cigarette use and the cognitive and behavioral aspects of
      smokers have conflicting results. This study highlights whether the use of e
      cigarettes can be used as an indicator for the readiness to quit smoking. Thus,
      counselors can encourage smoking cessation and provide tailored interventions.

PMID- 30235296
TI  - Multi-focus image fusion algorithm based on focus detection in spatial and NSCT
      domain.
AB  - Multi-focus image fusion is an effective approach to obtain the all-in-focus
      image. Focus detection is the key issue of multi-focus image fusion. Aiming at
      the shortcoming of spatial domain and transform domain algorithms for multi-focus
      image fusion, a novel multi-focus image fusion algorithm is proposed by combing
      focus detection in spatial domain and non-subsampled contourlet transform (NSCT)
      domain. At first, the focused pixels are detected by the sum-modified-Laplacian
      algorithm in spatial domain. At the same time, the focus detection method is
      proposed in NSCT domain, namely by MPCNN and voting fusion methods for high
      frequency subbands of NSCT. Then, the morphological operation is utilized to
      correct the focus detection results in spatial domain and NSCT domain. At last,
      synthesis of detection results is implemented and the fused image can be
      obtained. Experimental results verified that the proposed algorithm outperformed
      some state-of-the-art fusion algorithms in terms of both subjective observation
      and objective evaluations.

PMID- 30235297
TI  - Physicochemical and functional properties of Cucurbita maxima pumpkin pectin and
      commercial citrus and apple pectins: A comparative evaluation.
AB  - The physicochemical characteristics and functional properties of pumpkin
      (Cucurbita maxima D. var. Cabello de Angel) pectin obtained by cavitation
      facilitated extraction from pumpkin pulp have been evaluated and compared with
      commercial citrus and apple pectins. C. maxima pectin had an Mw value of 90 kDa
      and a high degree (72%) of esterification. The cytoprotective and antioxidant
      effects of citrus, apple and pumpkin pectin samples with different concentrations
      were studied in vitro in cell lines HT-29 (human colon adenocarcinoma) and MDCK1
      (canine kidney epithelium). All pectin samples exhibited cytoprotective effect in
      HT-29 and MDCK1 cells after incubation with toxic concentrations of cadmium and
      mercury for 4 h. Pumpkin pectin increased the proliferation of cadmium-treated
      MDCK1 cells by 210%. The studied pectins also inhibited oxidative stress induced
      by 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) in cell cultures,
      as determined by measuring the production of intracellular reactive species using
      dihydrochlorofluorescein diacetate (DCFH-DA). Pectin from pumpkin pomace had the
      highest (p < 0.05) protective effect against reactive oxygen species generation
      in MDCK1 cells induced by AAPH. Distinctive features of pumpkin pectin were
      highly branched RG-I regions, the presence of RG-II regions and the highest
      galacturonic acid content among the studied samples of pectins. This correlates
      with a considerable protective effect of C. maxima pectin against oxidative
      stress and cytotoxicity induced by heavy metal ions. Thus, C. maxima pectin can
      be considered as a source of new functional foods of agricultural origin.

PMID- 30235298
TI  - Influence of contextual variables and the pressure to keep category on physical
      match performance in soccer players.
AB  - Previous studies have analysed the influence of contextual variables on
      performance and physical demands in soccer. However, the points needed to remain
      in the category have been an element that has not been analysed previously. The
      aim of the present study was to investigate the influence of match location,
      match period, strength of the opponent and the points required to keep category
      on physical performance in professional soccer players. Fourteen Spanish second B
      Division League matches played by a professional football team were analysed
      during the 2016/17 season using GPS devices. The 10 main players of each match
      used the GPS throughout the match. The variables of Total Distance (m), High
      Intensity Distance (m), High intensity Accelerations (n), Sprint Time (s) and
      Sprint Distance (m) were analysed. The most notable differences are found in
      Total Distance covered. Away games accumulated significantly more distance than
      those played at home, but only in the second half (+230.65 m, IC95%: 21.94 to
      438.19, ES: 0.46, p = 0.031). There are no differences depending on the strength
      of the opponent. However, players covered greater distances during the first half
      in those matches that were played furthest from salvation (+235.86 m, 95% CI:
      49.03 to 422.70, ES: 0.51, p = 0.014). Total Distance is the main parameter
      affected by situational variables. In addition, the pressure of being further
      away from saving the category increases the distance covered by players in a
      game.

PMID- 30235299
TI  - Oxygen therapy may worsen the survival rate in rats with monocrotaline-induced
      pulmonary arterial hypertension.
AB  - Although oxygen therapy rapidly improves arterial oxygen saturation in idiopathic
      pulmonary arterial hypertension, the effects of chronic administration of oxygen
      are unknown. The purpose of the present study was to investigate the effects of
      chronic oxygen therapy on the histological changes and survival rate in rats with
      idiopathic pulmonary arterial hypertension. Idiopathic pulmonary arterial
      hypertension was induced by monocrotaline injection. The rats were then randomly
      assigned to receive or not receive oxygen therapy (O2 group and non-O2 group,
      respectively). The rats in the O2 group were exposed to a high (90%) oxygen
      environment from day 17 following injection of monocrotaline, when hypoxemia was
      first observed. The pulmonary arteriole walls were significantly thicker in
      monocrotaline-injected rats than in saline-injected rats as vehicle on day 19 and
      were significantly thicker in the rats that received oxygen therapy than in the
      rats that did not. Right ventricular inflammations were significantly higher in
      monocrotaline-injected rats than in saline-injected rats on day 19 and were
      significantly higher in the rats that received oxygen therapy than in the rats
      that did not. By day 20 after injection of monocrotaline, the survival rate was
      significantly lower in the rats that received oxygen therapy than in those that
      did not. Superoxide dismutase activity in the lungs was higher in monocrotaline
      injected rats than in saline-injected rats on day 19 after monocrotaline
      injection and was also higher in the saline-injected rats that received oxygen
      therapy than in the saline-injected rats that did not. No interaction was
      detected between monocrotaline injection and oxygen therapy. These results
      suggest that chronic oxygen therapy worsens the histological changes and survival
      rate in idiopathic pulmonary arterial hypertension. The fact that degradation of
      the histological changes and survival rate was accompanied by increase in
      superoxide dismutase activity suggests that antioxidant capacity may contribute
      to the degradation.

PMID- 30235300
TI  - Premature atrial and ventricular complexes in outpatients referred from a primary
      care facility.
AB  - BACKGROUND: Premature complexes are common electrocardiographic findings in daily
      clinical practice that require further evaluation. Investigation may sometimes be
      complex and expensive. The aim of our study was to analyze variables associated
      with premature beats identified in outpatients referred from a primary care
      facility. MATERIALS AND METHODS: We performed a cross-sectional study of 407
      outpatients (aged 55.8+/-11years; 56% women) who were followed by general
      practitioners and were referred for resting 12-lead electrocardiograms for a
      routine clinical follow-up. After signing informed consent, patients answered a
      questionnaire and underwent physical examinations, laboratory diagnostics,
      transthoracic echocardiograms and 24-hour Holter monitoring to evaluate for the
      presence of premature complexes. After the univariate analyses, logistic
      regression analyses were performed with adjustment for age, sex, and
      cardiovascular diseases. RESULTS: Premature complexes distribution revealed that
      they were frequent but with low density. Premature atrial complexes (>= 4/hours)
      were associated with age (Odds Ratio (OD) = 1.030, Confidence Interval (CI) 95% =
      1.002 ? 1.059, p = 0.029), brain natriuretic peptide (BNP) levels > 20mg/dL (OR =
      4.489, 95%CI = 1.918 ? 10.507, p = 0.0005), intraventricular blocks (OR = 4.184,
      95%CI = 1.816 ? 9.406, p = 0.0005) and left atrial diameter (OR = 1.065, 95%CI =
      1.001 ? 1.134, p = 0.046). Premature ventricular complexes (>= 5/hour) were
      related to age (OR = 1.032, 95%CI = 1.010 ? 1.054, p = 0.004), the use of calcium
      channel blockers (OR = 2.248, 95%CI = 1.019 ? 4.954, p = 0.045), HDL-cholesterol
      levels (OR = 0.971, 95%CI = 0.951 ? 0.992, p = 0.007), BNP levels > 20mg/dL (OR =
      2.079, 95%CI = 0.991 ? 0.998, p = 0.033), heart rate (OR = 1.019, 95%CI = 1.001 ?
      1.038, p = 0.041), left ventricular hypertrophy (OR = 2.292, 95%CI = 1.402 ?
      3.746, p = 0.001) and left ventricular ejection fraction (OR = 0.938, 95%CI =
      0.900 ? 0.978, p = 0.002). CONCLUSIONS: Premature complexes had low density and
      were associated with BNP levels > 20mg/dL, lower levels of HDL-cholesterol, left
      atrial enlargement and ventricular hypertrophy. The identification of premature
      complexes on 24-hour Holter monitor recordings of outpatients in a primary public
      healthcare setting was associated with uncontrolled cardiovascular risk factors
      that may be addressed with medical advice and therapy in a primary care setting.

PMID- 30235301
TI  - The structural equation model on self-efficacy during post-op rehabilitation
      among non-small cell lung cancer patients.
AB  - BACKGROUNDS: Self-efficacy plays an important role in pulmonary rehabilitation,
      but it is still unknown which factors exert their effects on postsurgical
      rehabilitation self-efficacy among non-small cell lung cancer (NSCLC) patients.
      This study aims to assess relationships among physical function, social factors,
      psychological factors, quality of life (QOL) and self-efficacy, and the effects
      of these variables on self-efficacy among NSCLC patients. METHODS: A cross
      sectional survey was administered to 238 postsurgical NSCLC patients (response
      rate 95.2%) at five tertiary hospitals in Fuzhou, China. the participants
      completed a pack of questionnaires. Structural equation modeling (SEM) was
      conducted to test the hypothetical model. RESULTS: The SEM results supported the
      hypothesized structural model (chi2/df = 1.511, p>0.05). The final model showed
      that confrontation coping, subjective well-being (SWB), social support,
      psychological growth (PTG) and anxiety and depression can be directly related to
      self-efficacy (coefficient = 0.335, coefficient = 0.288, coefficient = 0.150,
      coefficient = 0.024, and coefficient = -0.004, respectively, p<0.01).
      Confrontation coping also had indirect effect via SWB (coefficient = 0.085,
      p<0.01), which had indirect connection via PTG (coefficient = 0.005, p<0.01).
      Social support and anxiety and depression had indirect pathways as well. As
      expected, self-efficacy directly affected the quality of life. CONCLUSIONS: This
      study suggests that higher confrontation coping style, SWB, social support, and
      PTG and lower anxiety and depression levels could effectively enhance their self
      efficacy and consequently, improve QOL. These findings may help develop an
      intervention aimed at enhancing self-efficacy for this patient population.

PMID- 30235302
TI  - beta7 integrins contribute to intestinal tumor growth in mice.
AB  - The gut homing receptor integrin alpha4beta7 is essential for the migration of
      pro-inflammatory T cells into the gut mucosa. Since intestinal neoplasia has been
      associated with chronic inflammation, we investigated whether interfering with
      gut-homing affects intestinal tumorigenesis. Using chemically induced and
      spontaneous intestinal tumor models we showed that lack of beta7 integrin
      significantly impairs tumor growth without affecting tumor frequencies, with a
      mild translatable effect on overall survival. This correlates with human data
      showing lower MAdCAM-1 expression and disease-free survival in colorectal cancer
      patients. Thus, paradoxically in contrast to extra-intestinal tumors, blocking
      migration of immune cells into the gut might have a positive therapeutic effect
      on intestinal neoplasia.

PMID- 30235303
TI  - Contribution of 137Cs-enriched particles to radiocesium concentrations in
      seafloor sediment: Reconnaissance experiment.
AB  - Autoradiography was used to detect 137Cs-enriched particles in sediment samples.
      The contributions of 137Cs-enriched particles to 137Cs concentrations in sediment
      samples ranged from 9% to 64%. These experiments revealed that the variability of
      137Cs concentrations was due mainly to the heterogeneous distribution of 137Cs
      enriched particles in the samples. Therefore, the heterogeneous distribution of
      137Cs-enriched particles is probably one of the main factors responsible for the
      temporal and spatial variations of 137Cs concentrations in sediment samples.

PMID- 30235304
TI  - Improvements in the preparation of phosphate for oxygen isotope analysis from
      soils and sediments.
AB  - In contrast to the successful preparation of phosphate for oxygen isotope
      analysis from water samples, there are still a series of problems for similar
      analyses from soils and sediments. Here, we improved and optimized the methods of
      silver phosphate preparation for oxygen isotope analysis from soils and
      sediments. During our preparations, organic matter was removed by sodium
      hypochlorite and XAD-2 resin, while the impurities of elemental silver and its
      oxide were removed by rapid microprecipitation and ammonium phospho-molybdate and
      magnesium ammonium phosphate. The total organic carbon and total nitrogen in the
      prepared silver phosphates from soils and sediments were 0.226+/-0.033% and
      0.030+/-0.0059% (n = 7), 0.217+/-0.053% and 0.034+/-0.0120% (n = 9),
      respectively, indicating a high removal efficiency of organic matter. We
      confirmed that adding citric acid during rapid microprecipitation would introduce
      the impurity of elemental silver, which could be removed by ammonia
      recrystallization. The pH range of solutions for rapid microprecipitation was
      optimized at 7.0-7.5. Results of X-ray Diffraction and stable oxygen isotope
      analyses showed that the improved method could obtain high pure silver phosphate
      from soil and sediment samples without oxygen isotope fractionation. This
      improved procedure provides a foundation for biogeochemical studies on phosphorus
      in soil and lacustrine environments by using phosphate oxygen isotopes.

PMID- 30235306
TI  - Pointing to the right side? An ERP study on anaphora resolution in German Sign
      Language.
AB  - Sign languages use the horizontal plane to refer to discourse referents
      introduced at referential locations. However, the question remains whether the
      assignment of discourse referents follows a particular default pattern as
      recently proposed such that two new discourse referents are respectively assigned
      to the right (ipsilateral) and left (contralateral) side of (right handed)
      signers. The present event-related potential study on German Sign Language
      investigates the hypothesis that signers assign distinct and contrastive
      referential locations to discourse referents even in the absence of overt
      localization. By using a semantic mismatch-design, we constructed sentence sets
      where the second sentence was either consistent or inconsistent with the used
      pronoun. Semantic mismatch conditions evoked an N400, whereas a contralateral
      index sign engendered a Phonological Mismatch Negativity. The current study
      provides supporting evidence that signers are sensitive to the mismatch and make
      use of a default pattern to assign distinct and contrastive referential locations
      to discourse referents.

PMID- 30235305
TI  - In silico analysis of the Mus musculus uterine gene expression landscape during
      pregnancy identifies putative upstream regulators for labour.
AB  - BACKGROUND: The molecular pathways involved in the transition from uterine
      quiescence to overt labour are mapped and form the currently established
      pharmacological targets for both the induction and inhibition of human labour.
      However, both spontaneous premature labour and functional dystocia occur and are
      difficult to treat adequately. The identification of upstream regulators involved
      in the onset and orchestration of labour pathways is essential to develop
      additional therapies that will contribute to the regulation of the timing of
      birth. OBJECTIVES: To define uterine biological processes and their upstream
      activators involved in the transition from uterine quiescence to overt labour.
      STUDY DESIGN: The uterus of non-pregnant and pregnant FVB M. musculus is
      collected at embryonic days (E) 6.5, 8.5, 10.5, 12.5, 15.5 and 17.5 and the
      uterine transcriptome is determined using the Illumina mouse Ref8v2 micro-array
      platform. K-means clustering and Ingenuity Pathway Analysis are applied to
      further dissect the transcriptome data. RESULTS: From E6.5 to E17.5, 5405 genes
      are significantly differentially expressed and they segregate into 7 unique
      clusters. Five of the 7 clusters are enriched for genes involved in specific
      biological processes that include regulation of gene-expression, T-cell receptor
      activation, Toll-like receptor signalling and steroid metabolism. The
      identification of upstream activators for differentially expressed genes between
      consecutive time points highlights the E10.5 to E12.5 window during which the
      role from progesterone switches from an activated state to the inhibited state
      reflecting the process of functional progesterone withdrawal essential for the
      transgression from myometrial quiescence to synchronized contractions. For this
      time window in which 189 genes are differentially expressed we define 22 putative
      upstream activators of which NUPR1 and TBX2 are the most significant with
      respectively an activated and an inhibited status. CONCLUSIONS: Gene expression
      profiling of mice uterus from E6.5 to E17.5 results in 7 unique gene expression
      clusters from early to late pregnancy that define the landscape of molecular
      events in ongoing pregnancy. In the current dataset progesterone is predicted as
      an activated upstream regulator and maintainer of myometrial quiescence and is
      active till E10.5. Progesterone is predicted as an inhibited upstream regulator
      at E12.5. We identify 22 upstream regulators in the E10.5 to E12.5 time window
      where the switch to progesterone withdrawal occurs. They are putative relevant
      upstream activators of labour.

PMID- 30235307
TI  - Low-volume goat milk transmission of classical scrapie to lambs and goat kids.
AB  - The risk of classical scrapie transmission in small ruminants is highest during
      the neonatal period with the placenta recognized as a significant source of
      infection. Milk has also been identified as a source of scrapie with sheep-to
      sheep transmission occurring after neonatal consumption of as little as 1-2
      liters of milk; concurrent mastitis due to small ruminant lentivirus (SRLV)
      infection may be associated with increased scrapie transmission via milk in
      sheep. In contrast, goat-to-sheep transmission has been documented only after
      prolonged consumption of >30 liters of milk. The goal of the current study was to
      assess transmission of scrapie to goat kids and lambs following low volume, short
      duration consumption of milk from infected goats. Milk from two does (female
      goats) with pre-clinical scrapie was fed to four goat kids (<=4.5 L each) and
      four lambs (~3.7 L each) beginning ~24 hours after birth. Scrapie transmission
      was detected in three sheep as early as 18 months post inoculation; transmission
      was also detected in two goats but not until postmortem analyses at 33 months
      post inoculation. Each milk donor goat also had naturally-acquired infection with
      SRLV. Different degrees of lymphohistiocytic inflammation and PrPSc accumulation
      were observed in mammary gland tissues of the donors, which appeared to associate
      with transmission of scrapie via milk. Thus, similar to the risks of milk
      transmission of scrapie from sheep, even limited exposure to milk from goats can
      pose significant risk for scrapie transmission to both goat kids and lambs.

PMID- 30235310
TI  - Weed responses to fallow management in Pacific Northwest dryland cropping
      systems.
AB  - A two-year rotation of summer fallow (SF)/winter wheat (WW) is the most common
      cropping system in low precipitation areas of the U.S. Pacific Northwest (PNW).
      In SF, multiple tillage operations are used to manage weeds and maximize soil
      water storage and potential WW yield. Reduced tillage fallow (RTF) is an
      alternative to SF that leaves >30% of the previous crop's residue on the surface.
      A four-year (2014-18) field study was conducted to evaluate the influence of SF
      and RTF on weed species density, cover and composition in dryland WW; determine
      if changes in these weed infestation attributes have any influence on crop
      density and yield; and evaluate economic costs of each type of fallow management.
      The experimental design was randomized complete block with four replications
      where each phase of SF/WW and RTF/WW rotations was present every year. Individual
      plots of WW were divided into a weedy sub-plot with no weed control, general area
      with chemical weed control, and weed-free sub-plot where weeds were manually
      removed. Infestations of annual grass and other weeds in weedy sub-plots
      increased throughout the study. Grass weed cover, consisting mainly of downy
      brome (Bromus tectorum L.), and total weed cover were significantly lower in WW
      following RTF than following SF in all years except 2018. Densities of grass and
      total weeds were similar in both fallow managements indicating that weed plants
      were larger in WW following SF than following RTF due to earlier or faster
      emergence. Grass cover differences were not found in general areas likely because
      of a reduced seedbank. When weeds were present, mean yield of WW was higher
      following RTF than SF indicating that weeds were less competitive in RTF. Reduced
      tillage fallow could improve weed management in fallow/WW cropping systems of the
      PNW compared to SF/WW, particularly if the most problematic species are grasses.

PMID- 30235308
TI  - Preoperative and postoperative prediction of long-term meningioma outcomes.
AB  - BACKGROUND: Meningiomas are stratified according to tumor grade and extent of
      resection, often in isolation of other clinical variables. Here, we use machine
      learning (ML) to integrate demographic, clinical, radiographic and pathologic
      data to develop predictive models for meningioma outcomes. METHODS AND FINDINGS:
      We developed a comprehensive database containing information from 235 patients
      who underwent surgery for 257 meningiomas at a single institution from 1990 to
      2015. The median follow-up was 4.3 years, and resection specimens were re
      evaluated according to current diagnostic criteria, revealing 128 WHO grade I,
      104 grade II and 25 grade III meningiomas. A series of ML algorithms were trained
      and tuned by nested resampling to create models based on preoperative features,
      conventional postoperative features, or both. We compared different algorithms'
      accuracy as well as the unique insights they offered into the data. Machine
      learning models restricted to preoperative information, such as patient
      demographics and radiographic features, had similar accuracy for predicting local
      failure (AUC = 0.74) or overall survival (AUC = 0.68) as models based on
      meningioma grade and extent of resection (AUC = 0.73 and AUC = 0.72,
      respectively). Integrated models incorporating all available demographic,
      clinical, radiographic and pathologic data provided the most accurate estimates
      (AUC = 0.78 and AUC = 0.74, respectively). From these models, we developed
      decision trees and nomograms to estimate the risks of local failure or overall
      survival for meningioma patients. CONCLUSIONS: Clinical information has been
      historically underutilized in the prediction of meningioma outcomes. Predictive
      models trained on preoperative clinical data perform comparably to conventional
      models trained on meningioma grade and extent of resection. Combination of all
      available information can help stratify meningioma patients more accurately.

PMID- 30235311
TI  - Performance of the new clinical case definitions of pertussis in pertussis
      suspected infection and other diagnoses similar to pertussis.
AB  - BACKGROUND: In an effort to improve the pertussis diagnosis, the Global Pertussis
      Initiative (GPI) proposed an algorithm of the signs/symptoms of pertussis for
      three age groups: 0-3 months, 4 months to 9 years, and >=10 years of age.
      METHODS: We evaluated the accuracy of the clinical case definitions for pertussis
      proposed by the GPI using laboratory-confirmed pertussis as a reference standard
      for four groups: clinically suspected pertussis without comorbidity; asthma
      exacerbation; allergic constitution, and other diagnoses (bronchitis,
      bronchiolitis, laryngitis, and tracheitis). We included only patients who
      fulfilled one or more criteria of clinical case definitions for the age groups (0
      3 months, 4 months-9 years, and >=10 years of age). The data for this prospective
      epidemiological study were collected between 1st January 2013-31st December 2016
      at the outpatients and inpatients health care settings in the South Backa
      District of Autonomous Province of Vojvodina, Serbia. We evaluated accuracy of
      the certain sign and symptom combinations of GPI case definitions based on their
      sensitivity, specificity, and likelihood ratios. RESULTS: A total of 1043
      participants were included, with 306 (29.3%) laboratory-confirmed pertussis
      cases. In patients aged 0-3 months, whoop and apnoea associated with laboratory
      confirmation of pertussis. In patients aged 4 months-9 years with a pertussis
      suspicion infection or with one of the other diagnoses, the highest accuracy was
      found for whoop combined with apnoea or post-tussive emesis. In patients aged 10
      years and older, several different sign and symptom combinations were associated
      with an increased risk of pertussis among all enrolment diagnoses. There were
      fewer hospitalizations among the fully vaccinated children than in partly or
      unvaccinated children aged 4 months to 6 years (20.7% vs. 60.0%, p = 0.017).
      CONCLUSIONS: The numerous sign and symptom combinations in the observed case
      definitions were good predictors for laboratory-confirmed pertussis among all
      enrolment diagnoses, therefore suggesting the necessity for increased awareness
      of possibility for pertussis in patients with certain pertussis-like medical
      conditions.

PMID- 30235312
TI  - Mapping of B-cell epitopes on the N- terminal and C-terminal segment of
      nucleocapsid protein from Crimean-Congo hemorrhagic fever virus.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that
      causes severe disease in humans. CCHFV is widely distributed in more than 30
      countries and distinct regions, which means that it poses a serious threat to
      human health. The nucleocapsid protein (NP) encoded by the CCHFV S gene is the
      primary detectable antigen in infected cells, which makes it an important viral
      antigen and a clinical diagnostic target. In this study, the modified
      biosynthetic peptide (BSP) method was used to identify the fine epitopes on the N
      and C- terminals of NP from the CCHFV YL04057 strain using rabbit antiserum
      against CCHFV-NP. Nine epitopes were identified: E1a (178NLILNRGG185), E1b
      (184GGDENP189), E2 (352PLKWGKK358), E3 (363FADDS367), E4 (399NPDDAA404), E5a
      (447DIVASEHL454), E5b (452EHLLHQSL459), E6 (464SPFQNAY470) and E7
      (475NATSANII482). Western blotting analysis showed that each epitope interacted
      with the positive serum of sheep that had been naturally infected with CCHFV.
      Amino acid sequence alignment between each epitope and their homologous proteins
      showed that they were almost 100% conserved among 12 CCHFV sequences from
      different lineages, except for epitopes E1a, E1b and E2. Three-dimensional
      structural modeling analysis showed that all identified epitopes were located on
      the surface of the NP "head" domain. This study identified fine epitopes on the N
      and C- terminals of NP, which will increase the understanding of the structure
      and function of NP, and it could lay the foundation for the design and
      development of a CCHFV multi-epitope peptide vaccine and detection antigen.

PMID- 30235309
TI  - Multiple genomic regions influence root morphology and seedling growth in
      cultivated sunflower (Helianthus annuus L.) under well-watered and water-limited
      conditions.
AB  - With climate change and an ever-increasing human population threatening food
      security, developing a better understanding of the genetic basis of crop
      performance under stressful conditions has become increasingly important. Here,
      we used genome-wide association studies to genetically dissect variation in
      seedling growth traits in cultivated sunflower (Helianthus annuus L.) under well
      watered and water-limited (i.e., osmotic stress) conditions, with a particular
      focus on root morphology. Water limitation reduced seedling size and produced a
      shift toward deeper rooting. These effects varied across genotypes, and we
      identified 13 genomic regions that were associated with traits of interest across
      the two environments. These regions varied in size from a single marker to 186.2
      Mbp and harbored numerous genes, some of which are known to be involved in the
      plant growth/development as well as the response to osmotic stress. In many
      cases, these associations corresponded to growth traits where the common allele
      outperformed the rare variant, suggesting that selection for increased vigor
      during the evolution of cultivated sunflower might be responsible for the
      relatively high frequency of these alleles. We also found evidence of pleiotropy
      across multiple traits, as well as numerous environmentally independent genetic
      effects. Overall, our results indicate the existence of genetic variation in root
      morphology and allocation and further suggest that the majority of alleles
      associated with these traits have consistent effects across environments.

PMID- 30235313
TI  - Evolutionary history predicts the response of tree species to forest loss: A case
      study in peninsular Spain.
AB  - Evolutionary history can explain species resemblance to a large extent. Thus, if
      closely related species share combinations of traits that modulate their response
      to environmental changes, then phylogeny could predict species sensitivity to
      novel stressors such as increased levels of deforestation. To test this
      hypothesis, we used 66,949 plots (25-m-radius) of the Spanish National Forest
      Inventory and modelled the relationships between local (plot-level) stem density
      of 61 Holarctic tree species and forest canopy cover measured at local and
      landscape scales (concentric circles centred on the plots with radiuses of 1.6,
      3.2 and 6.4 km, respectively). Then, we used the output model equations to
      estimate the probability of occurrence of the species as a function of forest
      canopy cover (i.e. response to forest loss), and quantified the phylogenetic
      signal in their responses using a molecular phylogeny. Most species showed a
      lower probability of occurrence when forest canopy cover in the plots (local
      scale) was low. However, the probability of occurrence of many species increased
      when forest canopy cover decreased across landscape scales. We detected a strong
      phylogenetic signal in species response to forest loss at local and small
      landscape (1.6 km) scales. However, phylogenetic signal was weak and non
      significant at intermediate (3.2 km) and large (6.4 km) landscape scales. Our
      results suggest that phylogenetic information could be used to prioritize
      forested areas for conservation, since evolutionary history may largely determine
      species response to forest loss. As such, phylogenetically diverse forests might
      ensure contrasted responses to deforestation, and thus less abrupt reductions in
      the abundances of the constituent species.

PMID- 30235314
TI  - Forensic characterization and genetic polymorphisms of 19 X-chromosomal STRs in
      1344 Han Chinese individuals and comprehensive population relationship analyses
      among 20 Chinese groups.
AB  - X-chromosomal short tandem repeats (X-STRs) may assist resolution of complex
      forensic kinship cases and complement autosomal and Y-chromosomal STRs in routine
      forensic practice and population genetics. In the present study, we investigated
      the allele/haplotype diversity and forensic genetic characteristics of 19 X- STRs
      in 206 Guizhou Han and 1344 Meta-Han Chinese individuals using AGCU X19 PCR
      amplification system. Population relationships within five Han Chinese population
      groups (1344 individuals), between Guizhou Han and other 19 Chinese reference
      populations belonging to four language families (5074 individuals), as well as
      between Meta-Han Chinese and other 15 minorities (3730 individuals) were
      performed using Reynolds's, Nei's and Fst genetic distances, principal component
      analysis (PCA), multidimensional scaling (MDS), Structure and Neighbor-Joining
      tree. Mean paternity exclusion chance (MEC) in Duos > 0.99999999453588 and in
      trios > 0.99999999999781, as well as power of discrimination (PD) >
      0.99999999999980 in Guizhou Han on the basis of allele frequencies. Consistent
      high MECs and PDs can be observed in Meta-Han Chinese population based on both
      allele diversities of 19 markers and haplotype diversities of seven linkage
      groups (LG). DXS10135 and LG1 are the most informative and polymorphic in Han
      Chinese group. The comprehensive population comparisons reveal that Han Chinese
      is a homogenous population and has the genetically closer relationship with Hmong
      Mien-speaking groups than Tibetan-Burman-speaking and Turkic-speaking
      populations. In summary, AGCU X19 PCR amplification system is highly polymorphic
      and informative in Guizhou Han and Han Chinese populations. The comprehensive
      population data from 20 Chinese populations analyzed in this study may be used as
      a reference Chinese frequency database of X-STRs for forensic casework
      applications.

PMID- 30235315
TI  - Cerebral blood flow variability in fibromyalgia syndrome: Relationships with
      emotional, clinical and functional variables.
AB  - OBJECTIVE: This study analyzed variability in cerebral blood flow velocity (CBFV)
      and its association with emotional, clinical and functional variables and
      medication use in fibromyalgia syndrome (FMS). METHODS: Using transcranial
      Doppler sonography, CBFV were bilaterally recorded in the anterior (ACA) and
      middle (MCA) cerebral arteries of 44 FMS patients and 31 healthy individuals
      during a 5-min resting period. Participants also completed questionnaires
      assessing pain, fatigue, insomnia, anxiety, depression and health-related quality
      of life (HRQoL). RESULTS: Fast Fourier transformation revealed a spectral profile
      with four components: (1) a first very low frequency (VLF) component with the
      highest amplitude at 0.0024 Hz; (2) a second VLF component around 0.01-to-0.025
      Hz; (3) a low frequency (LF) component from 0.075-to-0.11 Hz; and (4) a high
      frequency (HF) component with the lowest amplitude from 0.25-to-0.35 Hz. Compared
      to controls, FMS patients exhibited lower LF and HF CBFV variability in the MCAs
      (p < .005) and right ACA (p = .03), but higher variability at the first right MCA
      (p = .04) and left ACA (p = .005) VLF components. Emotional, clinical and
      functional variables were inversely related to LF and HF CBFV variability (r>=
      .24, p<=.05). However, associations for the first VLF component were positive
      (r>=.28, p<=.05). While patients' medication use was associated with lower CBFV
      variability, comorbid depression and anxiety disorders were unrelated to
      variability. CONCLUSIONS: Lower CBFV variability in the LF and HF ranges were
      observed in FMS, suggesting impaired coordination of cerebral regulatory systems.
      CBFV variability was differentially associated with clinical variables as a
      function of time-scale, with short-term variability being related to better
      clinical outcomes. CBFV variability analysis may be a promising tool to
      characterize FMS pathology and it impact on facets of HRQoL.

PMID- 30235316
TI  - Elevated renal tissue oxygenation in premature fetal growth restricted neonates:
      An observational study.
AB  - BACKGROUND: Fetal growth restriction (FGR) is associated with an increased risk
      for kidney disease in later life. Studies reporting on early signs of renal
      disturbances in FGR are sparse and mostly include invasive measurements, which
      limit the possibility for early identification and prevention. We aim to
      investigate whether renal tissue oxygen saturation (rSO2) measured with near
      infrared spectroscopy (NIRS) and the derived value fractional tissue oxygen
      extraction (FTOE) differ between premature FGR and control neonates in the first
      three days after birth. METHODS: Nine FGR and seven control neonates born <32
      weeks of gestation were included. FGR was defined as biometry <p10 combined with
      prenatal signs of placental insufficiency. Renal rSO2 was measured continuously
      with NIRS for 72 hours. FTOE was calculated as: (arterial saturation
      rSO2)/arterial saturation. Renal artery blood flow (pulsatility and resistance
      index) was measured within 24 hours after birth. A linear mixed model approach
      was used (intercept +/- slope = r) to analyze the NIRS parameters. RESULTS: Renal
      rSO2 was higher in FGR neonates compared to controls (94% vs. 83%; pgroup =
      0.002). During the first three days after birth, renal rSO2 decreased in FGR
      neonates and increased in controls (r = -0.25 vs. r = 0.03; pinteraction =
      0.001). Renal FTOE was lower in FGR neonates (0.02 vs. 0.14; pgroup = 0.01) and
      increased slightly during three days after birth, while it remained stable in
      controls (r = 0.003 vs. r = -0.0001; pinteraction = 0.001). Renal artery blood
      flow was similar between groups. CONCLUSIONS: FGR neonate kidneys showed higher
      rSO2 as measured with NIRS and lower derived values of FTOE in the first three
      days after birth. We speculate that this was caused by either a reduced oxygen
      consumption due to impaired renal maturation or increased renal oxygen supply.
      How these observations correlate with short- and long-term renal function needs
      further investigation before renal NIRS can be implemented in screening and
      prevention in clinical practice.

PMID- 30235317
TI  - Behavioral immune system activity predicts downregulation of chronic basal
      inflammation.
AB  - Here, we present a mechanistically grounded theory detailing a novel function of
      the behavioral immune system (BIS), the psychological system that prompts
      pathogen avoidance behaviors. We propose that BIS activity allows the body to
      downregulate basal inflammation, preventing resultant oxidative damage to DNA and
      promoting longevity. Study 1 investigated the relationship between a trait
      measure of pathogen avoidance motivation and in vitro and in vivo proinflammatory
      cytokine production. Study 2 examined the relationship between this same
      predictor and DNA damage often associated with prolonged inflammation. Results
      revealed that greater trait pathogen avoidance motivation predicts a) lower
      levels of spontaneous (but not stimulated) proinflammatory cytokine release by
      peripheral blood mononuclear cells (PBMCs), b) lower plasma levels of the
      proinflammatory cytokine interleukin-6 (IL-6), and c) lower levels of oxidative
      DNA damage. Thus, the BIS may promote health by protecting the body from the
      deleterious effects of inflammation and oxidative stress.

PMID- 30235318
TI  - Variable pollen viability and effects of pollen load size on components of seed
      set in cultivars and feral populations of oilseed rape.
AB  - Pollination success is important for crop yield, but may be cultivar dependent.
      Less is known about which floral traits influence pollination success. Floral
      traits, e.g. traits related to attraction and reward, can also contribute to gene
      flow via pollen, the latter being of particular importance in oilseed rape
      (Brassica napus) where gene flow occurs between plants of crop, volunteer and
      feral origin as well as related taxa. We investigated the relationship between
      pollen load size and seed set in winter oilseed rape. We compared variability in
      pollen-viability traits, flower production (flowers from the main raceme times
      number of branches) and seed number and weight per siliqua among cultivars and
      feral populations (growing outside of agricultural fields) under controlled
      conditions. Both seed number and weight were saturated at relatively low pollen
      loads in the tested cultivar. Pollen viability and estimated flower production
      differed among cultivars, indicating that these traits could contribute to yield
      variability. Seed weight per siliqua, but not pollen traits or flower production,
      was lower in ferals compared to cultivars. Thus, while the probability of
      establishment may be reduced in ferals (due to lower seed weight per siliqua)
      this will not necessarily impact their contribution to gene flow via pollen. In
      oilseed rape a relatively low pollen load may be sufficient for full seed set in
      some cultivars, suggesting less dependence on insect pollination for high yield
      than generally expected. Our results also showed that previously less
      investigated floral traits, such as pollen viability, pollen tube growth rate and
      flower number, can differ between cultivars. Studies of these traits may provide
      targets for increasing crop yield and provide general knowledge about gene flow
      between cultivated, feral and related wild populations.

PMID- 30235320
TI  - A viral trigger for celiac disease.

PMID- 30235319
TI  - Salivary metabolite profiling distinguishes patients with oral cavity squamous
      cell carcinoma from normal controls.
AB  - Oral cavity squamous cell carcinoma (OCC) and oropharyngeal squamous cell
      carcinoma (OPC) are among the most common cancers worldwide and are associated
      with high mortality and morbidity. The purpose of this study is to identify
      potential biomarkers to distinguish OCC/OPC from normal controls and to
      distinguish OCC patients with and without nodal metastasis. We tested saliva
      samples from 101 OCC, 58 OPC, and 35 normal controls using four analytical
      platforms (NMR, targeted aqueous by LC-MS/MS, global aqueous and global
      lipidomics by LC-Q-TOF). Samples from OCC and normal controls were divided into
      discovery and validation sets. Using linear regression adjusting for age, sex,
      race and experimental batches, we found the levels of two metabolites (glycine
      and proline) to be significantly different between OCC and controls (FDR < 0.1
      for both discovery and validation sets) but did not find any appreciable
      differences in metabolite levels between OPC and controls or between OCC with and
      without nodal metastasis. Four metabolites, including glycine, proline,
      citrulline, and ornithine were associated with early stage OCC in both discovery
      and validation sets. Further study is warranted to confirm these results in the
      development of salivary metabolites as diagnostic markers.

PMID- 30235321
TI  - Thought experiment: Decoding cognitive processes from the fMRI data of one
      individual.
AB  - Cognitive processes, such as the generation of language, can be mapped onto the
      brain using fMRI. These maps can in turn be used for decoding the respective
      processes from the brain activation patterns. Given individual variations in
      brain anatomy and organization, analyzes on the level of the single person are
      important to improve our understanding of how cognitive processes correspond to
      patterns of brain activity. They also allow to advance clinical applications of
      fMRI, because in the clinical setting making diagnoses for single cases is
      imperative. In the present study, we used mental imagery tasks to investigate
      language production, motor functions, visuo-spatial memory, face processing, and
      resting-state activity in a single person. Analysis methods were based on
      similarity metrics, including correlations between training and test data, as
      well as correlations with maps from the NeuroSynth meta-analysis. The goal was to
      make accurate predictions regarding the cognitive domain (e.g. language) and the
      specific content (e.g. animal names) of single 30-second blocks. Four teams used
      the dataset, each blinded regarding the true labels of the test data. Results
      showed that the similarity metrics allowed to reach the highest degrees of
      accuracy when predicting the cognitive domain of a block. Overall, 23 of the 25
      test blocks could be correctly predicted by three of the four teams. Excluding
      the unspecific rest condition, up to 10 out of 20 blocks could be successfully
      decoded regarding their specific content. The study shows how the information
      contained in a single fMRI session and in each of its single blocks can allow to
      draw inferences about the cognitive processes an individual engaged in. Simple
      methods like correlations between blocks of fMRI data can serve as highly
      reliable approaches for cognitive decoding. We discuss the implications of our
      results in the context of clinical fMRI applications, with a focus on how
      decoding can support functional localization.

PMID- 30235322
TI  - GC4S: A bioinformatics-oriented Java software library of reusable graphical user
      interface components.
AB  - Modern bioinformatics and computational biology are fields of study driven by the
      availability of effective software required for conducting appropriate research
      tasks. Apart from providing reliable and fast implementations of different data
      analysis algorithms, these software applications should also be clear and easy to
      use through proper user interfaces, providing appropriate data management and
      visualization capabilities. In this regard, the user experience obtained by
      interacting with these applications via their Graphical User Interfaces (GUI) is
      a key factor for their final success and real utility for researchers. Despite
      the existence of different packages and applications focused on advanced data
      visualization, there is a lack of specific libraries providing pertinent GUI
      components able to help scientific bioinformatics software developers. To that
      end, this paper introduces GC4S, a bioinformatics-oriented collection of high
      level, extensible, and reusable Java GUI elements specifically designed to speed
      up bioinformatics software development. Within GC4S, developers of new
      applications can focus on the specific GUI requirements of their projects,
      relying on GC4S for generalities and abstractions. GC4S is free software
      distributed under the terms of GNU Lesser General Public License and both source
      code and documentation are publicly available at http://www.sing-group.org/gc4s.

PMID- 30235323
TI  - Comparison of success rates in eye drop instillation between sitting position and
      supine position.
AB  - PURPOSE: To compare the success rates of eye drop instillation in the sitting
      position and supine position among Japanese patients with ocular diseases
      (cataract, glaucoma, or retinal and vitreous diseases). METHODS: Patients who
      were hospitalized in Okayama University Hospital for eye surgery were studied.
      Instillation procedures of each patient in both the sitting and supine positions
      were recorded using a video camera at the time of instillation. We defined
      "success" when one drop fell accurately onto the ocular surface at the first
      attempt. Instillation of two or more drops, drops delivered to a site other than
      the eye surface, and touching the eyelashes, eyelids, or conjunctiva with the tip
      of the eye drop bottle were regarded as "failure". We excluded patients with
      vision below counting finger. RESULTS: One-hundred and two patients (54 males and
      58 females, aged 70.2 +/- 12.3 years) with ocular disease who were hospitalized
      for surgery (cataract: 61.8%, glaucoma: 15.7%, retinal and vitreous diseases:
      22.5%) were included in this prospective observational study. The mean duration
      of eye drop use was 3.1 +/- 5.2 years. The success rate of eye drop instillation
      was significantly higher in the supine position than in the sitting position
      (64.7% vs. 50%, P = 0.0039). The mean age was significantly higher in the failure
      group than in the success group (74.0 +/- 11.5 vs. 67.7 +/- 12.4 years, P =
      0.0085) for the sitting position, but not significantly different for the supine
      position (72.3 +/- 12.9 vs. 70.1 +/- 12.0 years, P = 0.3849). No significant
      differences in mean duration of drop use, mean corrected VA, and mean spherical
      equivalent refraction were observed between success and failure groups, for both
      sitting and supine positions. CONCLUSIONS: In the present study, the success rate
      of eye drop instillation was significantly higher when applied in the supine
      position than in the sitting position.

PMID- 30235324
TI  - Prevalence and predictors of hypertension in Namibia: A national-level cross
      sectional study.
AB  - BACKGROUND: Hypertension has been identified as the single greatest contributor
      to the global burden of disease and mortality, with estimates suggesting that the
      highest levels of blood pressure have shifted from high-income countries to low
      income countries in sub-Saharan Africa. While evidence suggests a remarkably high
      prevalence of hypertension among urban residents in Namibia, national estimates
      to inform on the country-level burden are lacking. This study estimates the
      prevalence and predictors of hypertension among Namibian adults. METHODS: The
      analysis is based on 1,795 women and 1,273 men aged 35-64 years from the
      nationally-representative 2013 Namibia Demographic and Health Survey. Odds radios
      and 95% confidence intervals were estimated using logistic regression. RESULTS:
      The age-standardized prevalence of hypertension was 46.0% (men vs. women: 46.1%
      vs. 46.0%). Mean systolic and diastolic blood pressures for the total population
      were 128.8 mmHg (95% CI 127.8-129.7) and 83.1 mmHg (95% CI 82.5-83.7),
      respectively. Mean systolic blood pressure was significantly lower among women
      (men vs. women: 130.9 mmHg vs. 127.4 mmHg; p<0.001). There were no statistically
      significant differences in mean diastolic blood pressure between men and women.
      Older age, urban residence, and being either overweight or obese were positively
      associated with the odds of hypertension (p<0.01). For women, the odds of
      hypertension were also significantly increased for those who were diabetic (i.e.
      had a fasting blood glucose level greater than 7.0 mmol/L) and reduced for those
      with higher levels of education. CONCLUSION: The prevalence of hypertension among
      Namibian adults is high and associated with metabolic and socio-demographic
      factors. Future research examining disease comorbidity and behavioral risk
      factors could better inform on the disease burden and help target resources to
      optimize prevention and control.

PMID- 30235325
TI  - Sensitivity analyses for improving sulfur management strategies in winter oilseed
      rape.
AB  - Because sulfur (S) depletion in soil results in seed yield losses and grain
      quality degradation, especially in high S-demanding crops such as oilseed rape
      (Brassica napus L.), monitoring S fertilisation has become a central issue. Crop
      models can be efficient tools to conduct virtual experiments under different
      fertilisation management strategies. Using the process-based model SuMoToRI, we
      aimed to analyse the impact of different S fertilisation strategies coupled with
      the variablility observed in major plant characteristics in oilseed rape i.e.
      radiation use efficiency (RUE), carbon (C) allocation to the leaves (beta) and
      specific leaf area (SLA) on plant performance-driven variables encompassing total
      biomass (TDW), S in the photosynthetic leaves (QSmobile.GL) and leaf area index
      (LAIGL). The contrasting S supply conditions differed in the amount of S (5
      levels), and the timing of application (at bolting and/or at flowering, which
      included a fractioned condition). For this purpose, we performed a global
      sensitivity analysis (GSA) and calculated two sensitivity indices i.e. the
      Partial Raw Correlation Coefficient (PRCC) and the Sobol index. The results
      showed that whatever the timing of S supply, TDW, LAIGL and QSmobile.GL increased
      as S input increased. For a given S supply, there was no difference in TDW, LAIGL
      and QSmobile.GL between a single and a fractioned supply. Moreover, delaying the
      supply until flowering reduced the TDW and LAIGL whereas QSmobile.GL increased.
      Results showed that RUE had the greatest impact on TDW under all levels of S
      supply and all application timings, followed by beta and SLA. RUE mostly impacted
      on QSmobile.GL, depending on S supply conditions, whereas it was the parameter
      with the least impact on LAIGL. Ultimately, our results provide strong evidence
      of optimised S fertilisation timings and plant characteristics that will guide
      producers in their agricultural practices by using specific varieties under
      constrained S fertilisation strategies.

PMID- 30235326
TI  - The risk of developing cancer following metal-on-metal hip replacement compared
      with non metal-on-metal hip bearings: Findings from a prospective national
      registry "The National Joint Registry of England, Wales, Northern Ireland and the
      Isle of Man".
AB  - BACKGROUND AND PURPOSE: Over 1 million metal-on-metal hip replacements were
      implanted. Even well-functioning implants produce wear debris that can cause
      tissue damage, disseminate and cause DNA damage. We aimed to establish if there
      was an association between metal-on-metal hip replacement and the risk of
      subsequently developing cancer compared with alternative hip replacements.
      METHODS: We performed a population based prospective longitudinal cohort study
      using data from the National Joint Registry linked to Hospital Episode Statistics
      (n = 403,881 patients). We examined the incidence of a new diagnosis of cancer in
      patients who received a metal-on-metal bearing in comparison with those who
      received a non metal-on-metal bearing. Kaplan-Meier estimates of time to first
      cancer diagnosis were used with Cox proportional hazards regression models to
      assess the effect on the time to cancer diagnosis for all cancer types,
      haematological, malignant melanoma, urinary tract cancers or prostate cancer in
      men. RESULTS: The maximum follow up available was 11.8 years with 25% of patients
      followed up for more than 6.8 years (mean follow up 4.6 years; median 4.3; IQR
      2.1-6.8; range 0.01-11.8). Analyses by gender that adjusted for age at primary
      and presence or absence of linked Welsh (PEDW) records showed no increase in the
      risk of developing cancer according to the bearing surface implanted for all
      cancers, haematological cancers, malignant melanoma, urinary tract cancers or
      prostate cancer in men. For patients receiving a second hip replacement, there
      was also no difference. CONCLUSION: We have demonstrated that there is currently
      no evidence of an increase in the risk of cancer following primary hip
      replacement according to the type of bearing material used. Although the risk of
      revision in metal-on-metal bearing hip replacements is higher, it is reassuring
      that the risk of a new diagnosis of cancer is not currently increased. Despite
      the long term follow up available in this study, the latency period for some
      cancers is very long and therefore continued monitoring is required to ensure no
      new patterns emerge that may indicate need for universal screening.

PMID- 30235328
TI  - The activated DNA double-strand break repair pathway in cumulus cells from aging
      patients may be used as a convincing predictor of poor outcomes after in vitro
      fertilization-embryo transfer treatment.
AB  - Women with advanced maternal age exhibit low anti-Mullerian hormone (AMH) levels
      and an altered follicular environment, which is associated with poor oocyte
      quality and embryonic developmental potential. However, the underlying mechanism
      is poorly understood. The present study aimed to assesswhether aging patients
      exhibit an activated DNA double-strandbreak (DSB) repair pathway in cumulus cells
      and thus, an association with poor outcomes after in vitro fertilization-embryo
      transfer (IVF-ET) treatment. Cumulus cells from young (<=29 y) and aging (>=37 y)
      human female patients were collected after oocyte retrieval. Our results
      indicated that aging patients showed a higher rate of gamma-H2AX-positive cells
      than in young patients (24.33+/-4.55 vs.12.40+/-2.31, P<0.05). We also found that
      the mRNA expression levels of BRCA1, ATM, MRE11 and RAD51 were significantly
      elevated in aging cumulus cells. Accordingly, significantly increased protein
      levels of phospho-H2AX, BRCA1, ATM, MRE11 and RAD51 could be observed in aging
      cumulus cells. Moreover, aging cumulus cells showed a more frequent occurrence of
      early apoptosis than young cumulus cells. This study found that increases in DSBs
      and the activation of the repair pathway are potential indicators that may be
      used to predictoutcomes after IVF-ET treatment.

PMID- 30235329
TI  - Neuroglobin correlates with cryptochrome-1 in obstructive sleep apnea with
      primary aldosteronism.
AB  - BACKGROUND: Neuroglobin (Ngb) is highly expressed in the suprachiasmatic nucleus,
      and can regulate Per1 gene expression. It is still not known whether Ngb also
      influences Cryptochrome (Cry). Cry is implicated in hypertension and primary
      aldosteronism (PA) in mice. There is a strong correlation between Obstructive
      Sleep Apnea (OSA) and PA. We propose to prove that Ngb and Cry play a role in OSA
      with PA. METHODS: Subjects were recruited consecutively from residents of
      Jakarta, Indonesia; subjects aged 30-65 years with moderate to severe OSA and
      hypertension were included in the study. OSA was diagnosed using an unattended
      type 2 portable monitor (Alice Pdx), hypertension was diagnosed when morning
      blood pressure exceeded 140/90 mmHg or when taking anti-hypertensive drugs. Serum
      concentration of aldosterone, renin, Cry1, Cry2 and Ngb protein were determined
      using ELISA method. Primary aldosteronism (PA) was defined as ARR >=20. RESULTS:
      Forty subjects were recruited, 26 male and 14 female, median age 52.5 years, BMI
      27.46 kg/m2, and AHI 34.8 times/hour. We found 16 subjects with PA and 24 non PA.
      Cry1 and Cry2 did not correlate with ARR in PA and non PA groups. Ngb correlated
      positively with Cry1 (Spearman's rho = 0.455, p = 0.038) but not Cry2 in PA
      patients. Cry1 concentration decreased in severe hypoxia. CONCLUSIONS: Ngb
      correlates with Cry1 in OSA with PA. There is no correlation between Cry1 or Cry2
      with PA.

PMID- 30235327
TI  - Molecular assays for antimalarial drug resistance surveillance: A target product
      profile.
AB  - Antimalarial drug resistance is a major constraint for malaria control and
      elimination efforts. Artemisinin-based combination therapy is now the mainstay
      for malaria treatment. However, delayed parasite clearance following treatment
      with artemisinin derivatives has now spread in the Greater Mekong Sub region and
      may emerge or spread to other malaria endemic regions. This spread is of great
      concern for malaria control programmes, as no alternatives to artemisinin-based
      combination therapies are expected to be available in the near future. There is a
      need to strengthen surveillance systems for early detection and response to the
      antimalarial drug resistance threat. Current surveillance is mainly done through
      therapeutic efficacy studies; however these studies are complex and both time-
      and resource-intensive. For multiple common antimalarials, parasite drug
      resistance has been correlated with specific genetic mutations, and the molecular
      markers associated with antimalarial drug resistance offer a simple and powerful
      tool to monitor the emergence and spread of resistant parasites. Different
      techniques to analyse molecular markers associated with antimalarial drug
      resistance are available, each with advantages and disadvantages. However,
      procedures are not adequately harmonized to facilitate comparisons between sites.
      Here we describe the target product profiles for tests to analyse molecular
      markers associated with antimalarial drug resistance, discuss how use of current
      techniques can be standardised, and identify the requirements for an ideal
      product that would allow malaria endemic countries to provide useful spatial and
      temporal information on the spread of resistance.

PMID- 30235330
TI  - Independent association of HLA-DPB1*02:01 with rheumatoid arthritis in Japanese
      populations.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune disease
      characterized with joint destructions; environmental and genetic factors were
      thought to be involved in the etiology of RA. The production of anti
      citrullinated peptide antibodies (ACPA) is specifically associated with RA. DRB1
      is associated with the susceptibility of RA, especially ACPA-positive RA
      [ACPA(+)RA]. However, a few studies reported on the independent associations of
      DPB1 alleles with RA susceptibility. Thus, we investigated the independent
      association of DPB1 alleles with RA in Japanese populations. METHODS: Association
      analyses of DPB1 were conducted by logistic regression analysis in 1667 RA
      patients and 413 controls. RESULTS: In unconditioned analysis, DPB1*04:02 was
      nominally associated with the susceptibility of ACPA(+)RA (P = 0.0021, corrected
      P (Pc) = 0.0275, odds ratio [OR] 1.52, 95% confidence interval [CI] 1.16-1.99). A
      significant association of DPB1*02:01 with the susceptibility of ACPA(+)RA was
      observed, when conditioned on DRB1 (Padjusted = 0.0003, Pcadjusted = 0.0040,
      ORadjusted 1.47, 95%CI 1.19-1.81). DPB1*05:01 was tended to be associated with
      the protection against ACPA(+)RA, when conditioned on DRB1 (Padjusted = 0.0091,
      Pcadjusted = 0.1184, ORadjusted 0.78, 95%CI 0.65-0.94). When conditioned on DRB1,
      the association of DPB1*04:02 with ACPA(+)RA was disappeared. No association of
      DPB1 alleles with ACPA-negative RA was detected. CONCLUSION: The independent
      association of DPB1*02:01 with Japanese ACPA(+)RA was identified.

PMID- 30235331
TI  - Health-related quality of life compared between kidney transplantation and
      nocturnal hemodialysis.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is an important outcome
      measure in patients with end-stage renal disease. HRQOL is assumed to improve
      with kidney transplantation and also with nocturnal hemodialysis compared to
      conventional hemodialysis. However, there is no evidence regarding HRQOL to
      support the optimal treatment choice for patients on nocturnal hemodialysis who
      hesitate opting for transplantation. We therefore compared HRQOL between patients
      who were treated with kidney transplantation or nocturnal hemodialysis for one
      year. METHODS: We assessed HQROL using the Kidney Disease Quality of Life-Short
      Form questionnaire in a cross-sectional sample of patients who were treated with
      kidney transplantation (n = 41) or nocturnal hemodialysis (n = 31) for one year.
      All patients on nocturnal hemodialysis were transplantation candidates. Using
      linear regression, we compared HRQOL between kidney transplantation and nocturnal
      hemodialysis, and adjusted for age, sex, dialysis duration, cardiovascular
      disease, and presence of residual urine production. RESULTS: At one year follow
      up, mean age of the study population was 54 +/-13 years, and median dialysis
      duration was 3.2 (IQR 2.1-5.0) years. Kidney transplantation was associated with
      significantly higher HRQOL on the domain "effects" compared to nocturnal
      hemodialysis (adjusted difference 12.0 points, 95% CI 3.9; 20.1). There were
      potentially clinically relevant differences between kidney transplantation and
      nocturnal hemodialysis on the domains "burden" (adjusted difference 11.1 points,
      95% CI -2.6; 24.8), "social support" (adjusted difference 6.2, 95% CI -6.6;
      19.1), and the physical composite score (adjusted difference 3.0, 95% CI -2.0;
      8.1), but these were not significant. CONCLUSIONS: After kidney transplantation,
      HRQOL is especially higher on the domain "effects of kidney disease" compared to
      nocturnal hemodialysis. This can be useful when counseling patients on nocturnal
      hemodialysis who may opt for transplantation.

PMID- 30235333
TI  - Temporal dynamics in animal community assembly during post-logging succession in
      boreal forest.
AB  - Species assemblages can result from deterministic processes, such as niche
      differentiation and interspecific interactions, and from stochastic processes,
      such as random colonisation and extinction events. Although changes in animal
      communities following disturbances have been widely examined, few studies have
      investigated the mechanisms structuring communities during ecological succession.
      We assessed the impact of logging on small mammal and beetle assemblages in
      landscapes dominated by old-growth boreal forests. Our objectives were to 1)
      characterize variations in communities during the first 66 years of post-harvest
      forest succession, 2) determine if there are non-random patterns of species co
      occurrence (i.e., deterministic processes), and if there are, 3) establish
      whether non-random co-occurrences are best explained by habitat attributes or by
      interspecific interactions. We captured small mammals and beetles along a
      gradient of forest succession (5-66 years) and in old-growth forest, and
      characterized key vegetation attributes. First, we tested whether community
      compositions in clear-cut stands became similar to those in natural stands after
      66 years. We then used null models, which were either unconstrained or
      constrained by habitat attributes, to address the last two objectives and
      distinguish effects of vegetation attributes from interspecific interactions on
      community assembly. We showed that beetle assemblages differed in stands 21-30
      years post-harvest compared to old-growth forests. In contrast, harvesting did
      not influence the composition of small mammal communities. Overall, our results
      suggest that community assembly during forest succession is driven by both
      stochastic and deterministic processes, the latter being linked to interspecific
      interactions more strongly than to vegetation attributes.

PMID- 30235332
TI  - Identification of endogenous normalizing genes for expression studies in inguinal
      ring tissue for scrotal hernias in pigs.
AB  - The use of reference genes is required for relative quantification in gene
      expression analysis and since the stability of these genes could be variable
      depending on the experimental design, it has become indispensable to test the
      reliability of endogenous genes. Therefore, this study evaluated 10 reference
      candidate genes in two different experimental conditions in order to obtain
      stable genes to be used as reference in expression studies related to scrotal
      hernias in pigs. Two independent experiments were performed: one with 30 days-old
      MS115 pigs and the other with 60 days-old Landrace pigs. The inguinal ring/canal
      was collected, frozen and further submitted to real-time PCR analysis (qPCR). For
      the reference genes stability evaluation, four tools were used: GeNorm in the
      SLqPCR, BestKeeper, NormFinder and Comparative CT. A general ranking was
      generated using the BruteAggreg function of R environment. In this study, the
      RPL19 was one of the most reliable endogenous genes for both experiments. The
      breed/age effects influenced the expression stability of candidate reference
      genes evaluated in the inguinal ring of pigs. Therefore, this study reinforces
      the importance of evaluating the stability of several endogenous genes previous
      their use, since a consensual set of reference genes is not easily obtained.
      Here, two sets of genes are recommended: RPL19, RPL32 and H3F3A for 30-days MS115
      and PPIA and RPL19 for the 60 days-old Landrace pigs. This is the first study
      using the inguinal ring tissue and the results can be useful as an indicative for
      other studies working with gene expression in this tissue.

PMID- 30235335
TI  - Molecular characterization of blood type A, B, and C (AB) in domestic cats and a
      CMAH genotyping scheme.
AB  - In domestic cats, the AB blood group system consists of the three types A, B, and
      C (usually called AB), which vary in frequency among breeds and geographic
      regions. Mismatches cause acute hemolytic transfusion reactions and hemolysis of
      the newborn due to the presence of naturally occurring anti-A alloantibodies.
      Cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) converts N
      acetylneuraminic acid (type B) to N-glycolylneuraminic acid (type A), and type C
      erythrocytes express both antigens. We examined the feline CMAH coding regions
      and genotyped cats to characterize type A, B, and C animals. Of 421
      phenotypically typed cats, 60% were A, 35% B and 5% C. Among the 70 cats for
      which the CMAH coding region was sequenced, 13 new variants were identified in
      addition to 16 of the previously reported 18 variants. The CMAH variant c.268T>A
      is seen in type B cats of most breeds, and the variant c.179G>T results in type B
      in Turkish breeds. The variants c.1322delT and c.933delA cause frameshifts with
      early stop codons and thereby type B in some Ragdolls and domestic shorthair
      cats, respectively. Protein modeling with PROVEAN affirmed their deleterious
      effects. No type A and C cats had more than one allele with one of the above
      variants. Variant analysis of three SNVs (c.142G>A, c.268T>A and Delta-53) and
      blood typing of an additional 351 typed cats showed complete phenotype-genotype
      concordance. In conclusion, the three CMAH variants c.179G>T, c.268T>A and
      c.1322delT are the main reasons for the defective NeuGc synthesis causing blood
      type B in domestic purebred and non-pedigreed cats. Together with the variant
      c.364C>T for type C in Ragdolls they offer a molecular screening scheme for
      clinical diagnostics to assure blood type compatibility.

PMID- 30235334
TI  - Manganese acquisition is essential for virulence of Enterococcus faecalis.
AB  - Manganese (Mn) is an essential micronutrient that is not readily available to
      pathogens during infection due to an active host defense mechanism known as
      nutritional immunity. To overcome this nutrient restriction, bacteria utilize
      high-affinity transporters that allow them to compete with host metal-binding
      proteins. Despite the established role of Mn in bacterial pathogenesis, little is
      known about the relevance of Mn in the pathophysiology of E. faecalis. Here, we
      identified and characterized the major Mn acquisition systems of E. faecalis. We
      discovered that the ABC-type permease EfaCBA and two Nramp-type transporters,
      named MntH1 and MntH2, work collectively to promote cell growth under Mn
      restricted conditions. The simultaneous inactivation of EfaCBA, MntH1 and MntH2
      (DeltaefaDeltamntH1DeltamntH2 strain) led to drastic reductions (>95%) in
      cellular Mn content, severe growth defects in body fluids (serum and urine) ex
      vivo, significant loss of virulence in Galleria mellonella, and virtually
      complete loss of virulence in rabbit endocarditis and murine catheter-associated
      urinary tract infection (CAUTI) models. Despite the functional redundancy of
      EfaCBA, MntH1 and MntH2 under in vitro or ex vivo conditions and in the
      invertebrate model, dual inactivation of efaCBA and mntH2 (DeltaefaDeltamntH2
      strain) was sufficient to prompt maximal sensitivity to calprotectin, a Mn- and
      Zn-chelating host antimicrobial protein, and for the loss of virulence in
      mammalian models. Interestingly, EfaCBA appears to play a prominent role during
      systemic infection, whereas MntH2 was more important during CAUTI. The different
      roles of EfaCBA and MntH2 in these sites could be attributed, at least in part,
      to the differential expression of efaA and mntH2 in cells isolated from hearts or
      from bladders. Collectively, this study demonstrates that Mn acquisition is
      essential for the pathogenesis of E. faecalis and validates Mn uptake systems as
      promising targets for the development of new antimicrobials.

PMID- 30235337
TI  - Epac1 protects the retina against ischemia/reperfusion-induced neuronal and
      vascular damage.
AB  - We had previously reported that exchange protein for cAMP 1 (Epac1) reduced
      inflammatory mediators in the retina of mice and in retinal endothelial cells
      (REC). Since ischemia can induce retinal damage potentially through activation of
      inflammatory cascades, we hypothesized that Epac1 would protect the retina
      against neuronal and vascular damage after exposure to ischemia/reperfusion
      (I/R). We used Epac1 floxed and endothelial cell specific Epac1 knockout mice for
      this work. We exposed them to ischemia for 90 minutes followed by reperfusion.
      One day after I/R, some mice were used for fluorescein angiography imaging or
      Evan's blue measurements of permeability. Mice were sacrificed at 2 days for
      neuronal measurements and at 10 days for measurements of degenerate capillaries.
      Data show increased leakage in the Epac1 Cre-Lox (Epac1 EC-KO) mice exposed to
      I/R when compared to Epac1 floxed mice with the same treatment. I/R also
      increased numbers of degenerate capillaries and cell loss in all retinal layers
      of Epac1 EC-KO mice. Retinal thickness was reduced more significantly in the
      Epac1 EC-KO mice compared to Epac1 floxed mice after I/R. Taken together, the
      data suggest that Epac1 is protective against both neuronal and vascular damage
      to the retina after exposure to I/R.

PMID- 30235336
TI  - SPIO labeling of endothelial cells using ultrasound and targeted microbubbles at
      diagnostic pressures.
AB  - In vivo cell tracking of therapeutic, tumor, and endothelial cells is an emerging
      field and a promising technique for imaging cardiovascular disease and cancer
      development. Site-specific labeling of endothelial cells with the MRI contrast
      agent superparamagnetic iron oxide (SPIO) in the absence of toxic agents is
      challenging. Therefore, the aim of this in vitro study was to find optimal
      parameters for efficient and safe SPIO-labeling of endothelial cells using
      ultrasound-activated CD31-targeted microbubbles for future MRI tracking.
      Ultrasound at a frequency of 1 MHz (10,000 cycles, repetition rate of 20 Hz) was
      used for varying applied peak negative pressures (10-160 kPa, i.e. low mechanical
      index (MI) of 0.01-0.16), treatment durations (0-30 s), time of SPIO addition (-5
      min- 15 min with respect to the start of the ultrasound), and incubation time
      after SPIO addition (5 min- 3 h). Iron specific Prussian Blue staining in
      combination with calcein-AM based cell viability assays were applied to define
      the most efficient and safe conditions for SPIO-labeling. Optimal SPIO labeling
      was observed when the ultrasound parameters were 40 kPa peak negative pressure
      (MI 0.04), applied for 30 s just before SPIO addition (0 min). Compared to the
      control, this resulted in an approximate 12 times increase of SPIO uptake in
      endothelial cells in vitro with 85% cell viability. Therefore, ultrasound
      activated targeted ultrasound contrast agents show great potential for effective
      and safe labeling of endothelial cells with SPIO.

PMID- 30235338
TI  - Correction: Temporal dynamics of in-situ fiber-adherent bacterial community under
      ruminal acidotic conditions determined by 16S rRNA gene profiling.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0182271.].

PMID- 30235339
TI  - Correction: Predictive value for cardiovascular events of common carotid intima
      media thickness and its rate of change in individuals at high cardiovascular risk
      - Results from the PROG-IMT collaboration.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191172.].

PMID- 30235340
TI  - Sentinel lymph node biopsy mapped with methylene blue dye alone in patients with
      breast cancer: A systematic review and meta-analysis.
AB  - BACKGROUND: Methylene blue dye is easy to obtain in developing countries and can
      be used in sentinel lymph node mapping for breast cancer. However, the accuracy
      of methylene blue alone for sentinel lymph node mapping in breast cancer has not
      been well defined. In this study, we collected data to assess the feasibility and
      accuracy of sentinel lymph node biopsy mapped with methylene blue alone in
      patients with breast cancer. METHODS: We searched the PubMed, EMBASE, and
      Cochrane Library databases from January 1, 1993, to March 31, 2018. Selected
      studies had to have a defined group of patients with breast cancer in which MBD
      alone was used as the mapping technique for SNB. RESULTS: 18 studies were
      included in this study. The combined identification rate was 91% [95% confidence
      interval (CI): 88%-94%, I2 = 68.3%], and the false negative rate was 13% (95% CI:
      9%-18%, I2 = 36.7%). The pooled sensitivity, negative predictive value, and
      accuracy rate were 87% (95% CI: 82%-91%, I2 = 37.5%), 91% (95% CI: 87%-93%, I2 =
      32.4%) and 94% (95% CI: 92%-96%, I2 = 29%), respectively. CONCLUSIONS: This meta
      analysis found that mapping sentinel lymph node locations with methylene blue dye
      alone results in an acceptable identification rate but an excessive false
      negative rate according to the American Society of Breast Surgeons'
      recommendations. Caution is warranted when using methylene blue dye alone as the
      mapping method for sentinel lymph node biopsy.

PMID- 30235341
TI  - Biofilm formation and potential virulence factors of Salmonella strains isolated
      from ready-to-eat shrimps.
AB  - Salmonella species is an important foodborne pathogen with the non-typhoidal
      serovars such as Enteritidis and Typhimurium as the most predominant strains.
      This study examines the biofilm formation, phenotypic virulence factors and cell
      surface characteristics of Salmonella strains from ready-to-eat shrimps. The
      ready-to-eat shrimps were obtained from open markets between November 2016 and
      October 2017 in Edo and Delta States, Nigeria. The occurrence of Salmonella
      strains in this study was 210/1440 (14.58%) of the ready-to-eat shrimp's samples.
      The identified strains comprise of Salmonella Enteritidis 11, Salmonella
      Typhimurium 14 and other Salmonella spp. 20. The 45 identified Salmonella strains
      revealed the following virulence properties: swimming and swarming motility
      45(100%); S-layer 39(86.67%); haemolytic activity 40(88.89%); lipase activity
      43(95.56%); protease activity 43(95.56%); gelatinase production 43(95.56%); and
      DNA degrading activity 41(91.11%). The variation in the formation of biofilm
      based on the diversity of Salmonella species was observed with higher percentage
      of Salmonella Typhimurium strains as strong biofilms producers under different
      environmental conditions. For surface hydrophobicity using bacterial adherence to
      hydrocarbons, 25(55.56%) were hydrophilic while 20(44.44%) were moderately
      hydrophobic from the 45 Salmonella isolates. Using salting aggregation test for
      surface hydrophobicity, all selected isolates 45(100%) was hydrophilic.
      Autoaggregation index for the 12 selected Salmonella isolates ranged from 15.2
      47.2%, while the autoaggragation index for the 12 selected test bacteria ranged
      from 26.2-71.3%. Coaggragation between the 12 selected test bacteria and 12
      Salmonella isolates ranged from 12.5-81.0%. The occurrence of pathogenic species
      of Salmonella from ready-to-eat shrimps could be detrimental to the consumers.
      Findings on the physiological conditions of biofilms formed by the foodborne
      pathogenic Salmonella and the cell surface characteristics therein are crucial
      for the advancement of methods for controlling Salmonella from ready-to-eat
      foods.

PMID- 30235342
TI  - Persistent circulation of genotype D coxsackievirus A2 in mainland of China since
      2008.
AB  - Coxsackievirus A2 (CV-A2) has emerged as an important etiological agent in the
      hand, foot, and mouth disease and herpangina pathogen spectrum because of its
      high global prevalence. In the present study, we investigated the evolutionary
      dynamics of CV-A2 circulating in China. We analyzed a total of 163 entire VP1
      sequences of CV-A2, including 74 sequences generated from the present study and
      89 sequences collected from the GenBank database. Phylogenetic analysis based on
      the entire VP1 nucleotide sequences confirmed the persistent circulation of the
      predominant genotype D in mainland of China since 2008. Cluster analysis grouped
      the sequences into two distinct clusters, clusters 1 and 2, with most grouped
      under cluster 2. After 2012, cluster 1 was gradually replaced by cluster 2.
      Results of Bayesian Markov chain Monte Carlo analysis suggested that multiple
      lineages of genotype D were transmitted in mainland of China at an estimated
      evolutionary rate of 6.32*10-3 substitutions per site per year, which is
      consistent with the global evolutionary rate of CV-A2 (5.82*10-3 substitutions
      per site per year). Continuous transmission and evolution of CV-A2 resulted in
      the genetic polymorphism.

PMID- 30235344
TI  - Correction: Robust CPD Algorithm for Non-Rigid Point Set Registration Based on
      Structure Information.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0148483.].

PMID- 30235343
TI  - Gender differences in the relationships between perceived individual-level
      occupational stress and hazardous alcohol consumption among Japanese teachers: A
      cross-sectional study.
AB  - Most teachers have a high risk of work-related stress and mental disorders.
      Drunken driving and hazardous alcohol consumption (HAC) among teachers are social
      problems. Gender differences among teachers in burnout, occupational stress, self
      efficacy and job satisfaction were reported. This study aimed to clarify gender
      differences in the relationships between perceived individual-level occupational
      stress and HAC among Japanese teachers. A cross-sectional study was conducted in
      2013 and a total of 723 male and 476 female teachers remained after excluding non
      drinkers. Perceived individual-level occupational stress was assessed using the
      Generic Job Stress Questionnaire. HAC was defined as ethanol consumption greater
      than or equal to 280 g in 1 week for male teachers, and greater than or equal to
      210 g for female teachers. Multiple logistic regression analyses were conducted.
      HAC was identified in 16.6% of male and 12.4% of female teachers. The average
      ages (+/- standard deviation: SD) of male and female teachers were 46.9 +/- 10.9
      years and 39.9 +/- 12.3 years, respectively. Schoolteacher was the most common
      position classification among male (48.7%) and female teachers (86.3%). For those
      with a moderate level of stress, "social support from supervisors" was associated
      with HAC among males (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.23
      0.8), whereas for female teachers with a high level of stress, "variance in
      workload" was associated with HAC (OR = 2.09, 95% CI = 1.04-4.24), using an
      adjusted model. This study showed that moderate social support from supervisors
      was negatively related to HAC among male teachers, and high variance in workload
      was positively related to HAC among female teachers. Gender differences need to
      be considered when developing HAC prevention strategies for teachers.

PMID- 30235345
TI  - Retraction: Survival Analysis of Adult Tuberculosis Disease.

PMID- 30235346
TI  - Correction: Arboreal crops on the medieval Silk Road: Archaeobotanical studies at
      Tashbulak.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0201409.].

PMID- 30235347
TI  - Dog ownership satisfaction determinants in the owner-dog relationship and the
      dog's behaviour.
AB  - Dog ownership satisfaction relates to the quality of life of both owner and dog,
      and when seriously compromised may even lead to dog abandonment. Knowledge on
      determinants of dog ownership satisfaction is limited, obstructing solutions for
      promoting satisfaction, and here we quantified causes making dog owners less than
      very satisfied with their dog. We focused on the owner perceived relationship
      with the dog, unwanted dog behaviour, and dog obedience class attendance. The
      study population included only few seriously dissatisfied dog owners, preventing
      discrimination of multiple levels below 'very satisfied'. Consequently, existing
      relationships in the entire population may have been missed or underestimated and
      the findings apply specifically to dog owners that are relatively contented with
      dog ownership. Nine hundred seventy-seven Dutch dog owners completed an online
      questionnaire and we found the probability of being very satisfied to associate
      with all three subscales of the Monash Dog Owner Relationship Scale. Most
      strongly with perceived costs of ownership and less so with shared activities
      between owner and dog, and perceived emotional closeness to the dog. Aggression
      and/or disobedience related directly to high perceived ownership costs and to an
      increased probability of being less than very satisfied. Interaction effects
      indicated that dog disobedience was less influential on ownership satisfaction at
      high levels of aggression. Surprisingly, dog ownership satisfaction was unrelated
      to dog obedience class attendance, raising questions about the effectiveness of
      these classes in establishing satisfying dog-owner relationships. Training aids
      used during classes could play a role here, as choke chain use associated with
      high perceived costs and increased probabilities of being less then very
      satisfied with dog ownership. Ownership satisfaction in relatively contented dog
      owners, seems more influenced by unwanted dog behaviour and perceived costs of
      ownership, than by perceived emotional closeness to the dog, shared activities
      and dog obedience class attendance.

PMID- 30235348
TI  - Systemic redox status in lung cancer patients is related to altered glucose
      metabolism.
AB  - Altered systemic redox status is often observed in lung cancer. However, detailed
      information on factors other, than smoking, which influence this perturbation is
      rather scarce. Elevated oxidative stress has been linked with disturbances in
      glucose metabolism before, but such associations have not been investigated in
      lung cancer. The aim of this study was to evaluate the relationship between
      systemic parameters of glucose metabolism and redox status in lung cancer
      patients (LC). Biochemical variables related to circulating glucose, i.e.
      glucose, insulin, c-peptide, fructosamine (FA), and glucose metabolism, i.e. beta
      hydroxybutyrate (BHB), lactate (LACT), non-esterified fatty acids (NEFAs), as
      well as redox status i.e. total antioxidant status (TAS) and total oxidant status
      (TOS) were determined for LC (n = 122) and control subjects (CS) (n = 84). HOMA
      IR and the oxidative stress index (OSI) were calculated. LC patients had an
      altered redox status and glucose metabolism compared to CS. Positive correlations
      in LC were observed between TOS, OSI and circulating glucose as well as FA, while
      TAS positively correlated with BHB and NEFAs. In contrast, in metastatic LC,
      NEFAs and BHB positively correlated with OSI. Smoking status additionally
      stratified the observed relationships. In conclusion, we found that parameters
      related to circulating glucose or non-enzymatic glycation were correlated with
      oxidative stress (TOS and OSI), while metabolites such as BHB and NEFAs were
      correlated with antioxidant capacity (TAS). Metastasis prevalence and smoking
      seem to influence these correlations. However, the detailed mechanism of this
      relationship requires further research, in particular as regards the surprising
      positive correlation between NEFAs and TAS.

PMID- 30235349
TI  - Temporal and molecular dynamics of human metastatic breast carcinoma cell
      adhesive interactions with human bone marrow endothelium analyzed by single-cell
      force spectroscopy.
AB  - Bone is a common site of metastasis for breast cancer and the mechanisms of
      metastasis are not fully elucidated. The purpose of our study was to characterize
      temporal and molecular dynamics of adhesive interactions between human breast
      cancer cells (HBCC) and human bone marrow endothelium (HBME) with piconewton
      resolution using atomic force microscopy (AFM). In adhesion experiments, a single
      breast cancer cell, MDA-MB-231 (MB231) or MDA-MB-435 (MB435) was attached to the
      AFM cantilever and brought into contact with a confluent HBME monolayer for
      different time periods (0.5 to 300 sec). The forces required to rupture
      individual molecular interactions and completely separate interacting cells were
      analyzed as measures of cell-cell adhesion. Adhesive interactions between HBME
      and either MB231 or MB435 cells increased progressively as cell-cell contact time
      was prolonged from 0.5 to 300 sec due to the time-dependent increase in the
      number and frequency of individual adhesive events, as well as to the involvement
      of stronger ligand-receptor interactions over time. Studies of the individual
      molecule involvement revealed that Thomsen-Friedenreich antigen (TF-Ag), galectin
      3, integrin-beta1, and integrin-alpha3 are all contributing to HBCC/HBME adhesion
      to various degrees in a temporally defined fashion. In conclusion, cell-cell
      contact time enhances adhesion of HBCC to HBME and the adhesion is mediated, in
      part, by TF-Ag, galectin-3, integrin-alpha3, and integrin-beta1.

PMID- 30235350
TI  - There was collusion: Microbes in inflammatory bowel disease.

PMID- 30235351
TI  - Expansion of commensal fungus Wallemia mellicola in the gastrointestinal
      mycobiota enhances the severity of allergic airway disease in mice.
AB  - The gastrointestinal microbiota influences immune function throughout the body.
      The gut-lung axis refers to the concept that alterations of gut commensal
      microorganisms can have a distant effect on immune function in the lung.
      Overgrowth of intestinal Candida albicans has been previously observed to
      exacerbate allergic airways disease in mice, but whether subtler changes in
      intestinal fungal microbiota can affect allergic airways disease is less clear.
      In this study we have investigated the effects of the population expansion of
      commensal fungus Wallemia mellicola without overgrowth of the total fungal
      community. Wallemia spp. are commonly found as a minor component of the commensal
      gastrointestinal mycobiota in both humans and mice. Mice with an unaltered gut
      microbiota community resist population expansion when gavaged with W. mellicola;
      however, transient antibiotic depletion of gut microbiota creates a window of
      opportunity for expansion of W. mellicola following delivery of live spores to
      the gastrointestinal tract. This phenomenon is not universal as other commensal
      fungi (Aspergillus amstelodami, Epicoccum nigrum) do not expand when delivered to
      mice with antibiotic-depleted microbiota. Mice with Wallemia-expanded gut
      mycobiota experienced altered pulmonary immune responses to inhaled
      aeroallergens. Specifically, after induction of allergic airways disease with
      intratracheal house dust mite (HDM) antigen, mice demonstrated enhanced
      eosinophilic airway infiltration, airway hyperresponsiveness (AHR) to
      methacholine challenge, goblet cell hyperplasia, elevated bronchoalveolar lavage
      IL-5, and enhanced serum HDM IgG1. This phenomenon occurred with no detectable
      Wallemia in the lung. Targeted amplicon sequencing analysis of the
      gastrointestinal mycobiota revealed that expansion of W. mellicola in the gut was
      associated with additional alterations of bacterial and fungal commensal
      communities. We therefore colonized fungus-free Altered Schaedler Flora (ASF)
      mice with W. mellicola. ASF mice colonized with W. mellicola experienced enhanced
      severity of allergic airways disease compared to fungus-free control ASF mice
      without changes in bacterial community composition.

PMID- 30235353
TI  - Correction: A Biologically-Inspired Symmetric Bidirectional Switch.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0169856.].

PMID- 30235354
TI  - Impact of cigarette taxes on smoking prevalence from 2001-2015: A report using
      the Behavioral and Risk Factor Surveillance Survey (BRFSS).
AB  - OBJECTIVES: To provide an up-to-date analysis on the relationship between excise
      taxes and the prevalence of cigarette smoking in the United States. METHODS:
      Linear mixed-effects models were used to model the relationship between excise
      taxes and prevalence of cigarette smoking in each state from 2001 through 2015.
      RESULTS: From 2001 through 2015, increases in state-level excise taxes were
      associated with declines in prevalence of cigarette smoking. The effect was
      strongest in young adults (age 18-24) and weakest in low-income individuals
      (<$25,000). CONCLUSIONS: Despite the shrinking pool of current smokers, excise
      taxes remain a valuable tool in public-health efforts to reduce the prevalence of
      cigarette smoking. POLICY IMPLICATIONS: States with high smoking prevalence may
      find increased excise taxes an effective measure to reduce population smoking
      prevalence. Since the effect is greatest in young adults, benefits of increased
      tax would likely accumulate over time by preventing new smokers in the pivotal
      young-adult years.

PMID- 30235352
TI  - Promyelocytic leukemia (PML) nuclear bodies (NBs) induce latent/quiescent HSV-1
      genomes chromatinization through a PML NB/Histone H3.3/H3.3 Chaperone Axis.
AB  - Herpes simplex virus 1 (HSV-1) latency establishment is tightly controlled by
      promyelocytic leukemia (PML) nuclear bodies (NBs) (or ND10), although their exact
      contribution is still elusive. A hallmark of HSV-1 latency is the interaction
      between latent viral genomes and PML NBs, leading to the formation of viral DNA
      containing PML NBs (vDCP NBs), and the complete silencing of HSV-1. Using a
      replication-defective HSV-1-infected human primary fibroblast model reproducing
      the formation of vDCP NBs, combined with an immuno-FISH approach developed to
      detect latent/quiescent HSV-1, we show that vDCP NBs contain both histone H3.3
      and its chaperone complexes, i.e., DAXX/ATRX and HIRA complex (HIRA, UBN1,
      CABIN1, and ASF1a). HIRA also co-localizes with vDCP NBs present in trigeminal
      ganglia (TG) neurons from HSV-1-infected wild type mice. ChIP and Re-ChIP show
      that vDCP NBs-associated latent/quiescent viral genomes are chromatinized almost
      exclusively with H3.3 modified on its lysine (K) 9 by trimethylation, consistent
      with an interaction of the H3.3 chaperones with multiple viral loci and with the
      transcriptional silencing of HSV-1. Only simultaneous inactivation of both H3.3
      chaperone complexes has a significant impact on the deposition of H3.3 on viral
      genomes, suggesting a compensation mechanism. In contrast, the sole depletion of
      PML significantly impacts the chromatinization of the latent/quiescent viral
      genomes with H3.3 without any overall replacement with H3.1. vDCP NBs-associated
      HSV-1 genomes are not definitively silenced since the destabilization of vDCP NBs
      by ICP0, which is essential for HSV-1 reactivation in vivo, allows the recovery
      of a transcriptional lytic program and the replication of viral genomes.
      Consequently, the present study demonstrates a specific chromatin regulation of
      vDCP NBs-associated latent/quiescent HSV-1 through an H3.3-dependent HSV-1
      chromatinization involving the two H3.3 chaperones DAXX/ATRX and HIRA complexes.
      Additionally, the study reveals that PML NBs are major actors in latent/quiescent
      HSV-1 H3.3 chromatinization through a PML NB/histone H3.3/H3.3 chaperone axis.

PMID- 30235356
TI  - Comprehensive molecular characterization of microneedling therapy in a human
      three-dimensional skin model.
AB  - BACKGROUND AND OBJECTIVES: Microneedling therapy is a widely used technique in
      dermatology. However, little is known about the underlying molecular effects of
      this therapy on extracellular matrix remodeling, wound healing, and inflammation.
      The aim of this study was to examine morphological and molecular changes caused
      by microneedling treatment in a standardized in vitro full-thickness 3D model of
      human skin. MATERIALS AND METHODS: A microneedling device was used to treat full
      thickness 3D skin models. Specimens were harvested at specified time points and
      qRT-PCR and microarray studies were performed. Frozen sections were examined
      histologically. RESULTS: Microneedling treatment caused morphological changes in
      the skin model resulting in an almost complete recovery of the epidermis five
      days after treatment. Microarray analysis identified an upregulation of genes
      that are associated with tissue remodeling and wound healing (e.g. COL3A1,
      COL8A1, TIMP3), epithelial proliferation and differentiation (KRT13, IGF1),
      immune cell recruitment (CCL11), and a member of the heat shock protein family
      (HSPB6). On the other hand, we detected a downregulation of pro-inflammatory
      cytokines (e.g. IL1alpha, IL1beta, IL24, IL36gamma, IL36RN), and antimicrobial
      peptides (e.g. S100A7A, DEFB4). These data were confirmed by independent RT-PCR
      analyses. CONCLUSION: We present for the first time the direct molecular effects
      of microneedling therapy on epidermal keratinocytes and dermal fibroblasts using
      a standardized 3D skin model. Treatment resulted in histological alterations and
      changed the expression of various genes related to epidermal differentiation,
      inflammation, and dermal remodeling. This data suggests that skin microneedling
      plays a role in dermal remodeling, increases epidermal differentiation, and might
      also have a direct effect on collagen synthesis. These findings may increase our
      understanding of the molecular mechanisms of human skin repair induced by
      microneedling therapy and will allow comparisons with competing applications,
      such as ablative laser therapies.

PMID- 30235355
TI  - Prions activate a p38 MAPK synaptotoxic signaling pathway.
AB  - Synaptic degeneration is one of the earliest pathological correlates of prion
      disease, and it is a major determinant of the progression of clinical symptoms.
      However, the cellular and molecular mechanisms underlying prion synaptotoxicity
      are poorly understood. Previously, we described an experimental system in which
      treatment of cultured hippocampal neurons with purified PrPSc, the infectious
      form of the prion protein, induces rapid retraction of dendritic spines, an
      effect that is entirely dependent on expression of endogenous PrPC by the target
      neurons. Here, we use this system to dissect pharmacologically the underlying
      cellular and molecular mechanisms. We show that PrPSc initiates a stepwise
      synaptotoxic signaling cascade that includes activation of NMDA receptors,
      calcium influx, stimulation of p38 MAPK and several downstream kinases, and
      collapse of the actin cytoskeleton within dendritic spines. Synaptic degeneration
      is restricted to excitatory synapses, spares presynaptic structures, and results
      in decrements in functional synaptic transmission. Pharmacological inhibition of
      any one of the steps in the signaling cascade, as well as expression of a
      dominant-negative form of p38 MAPK, block PrPSc-induced spine degeneration.
      Moreover, p38 MAPK inhibitors actually reverse the degenerative process after it
      has already begun. We also show that, while PrPC mediates the synaptotoxic
      effects of both PrPSc and the Alzheimer's Abeta peptide in this system, the two
      species activate distinct signaling pathways. Taken together, our results provide
      powerful insights into the biology of prion neurotoxicity, they identify new,
      druggable therapeutic targets, and they allow comparison of prion synaptotoxic
      pathways with those involved in other neurodegenerative diseases.

PMID- 30235357
TI  - Flu's cues: Exploiting host post-translational modifications to direct the
      influenza virus replication cycle.

PMID- 30235358
TI  - Role of Apolipoprotein E gene polymorphism in the risk of familial
      hypercholesterolemia: a case-control study.
AB  - Familial Hypercholesterolemia (FH) is characterized by elevated cholesterol and
      based on biochemical, clinical, and genetic studies and FH disease, which was
      documented even with limited mutations. Earlier studies focused on Apolipoprotein
      E (ApoE) in variable diseases. The current study aimed to investigate the genetic
      association between FH disease and ApoE gene polymorphisms (rs429358 and rs7412)
      in the Saudi population. This case-control study was a hospital-based study
      performed in Saudi Arabia. Two hundred and four subjects in total were recruited
      and consisted of FH participants (n=104) and the controls (n=100). Common
      polymorphisms of ApoE gene (rs429358 and rs7412) were chosen and subjected to the
      genotyping using the TaqMan assay. Moreover, the ApoE risk allele E4 was proved
      significantly associated with FH cases when compared with controls (OR-2.24
      (95%CI: 1.06-4.70); p=0.02). Lipid profile parameters were significantly
      associated (p<0.05); however, the ApoE alleles and lipid profiles were not
      correlated (p>0.05). In conclusion, the FH case-control study was associated with
      the E4 allele in the Saudi population. However, E4 allele was appeared as a
      reliable risk marker for lipid profiles, but not for ApoE alleles.

PMID- 30235359
TI  - Inflammatory linear verrucous epidermal nevus responsive to 308-nm excimer laser
      treatment.
AB  - Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare cutaneous disease
      that presents as linear psoriasiform plaques with associated prominent pruritus.
      The lesions commonly pre-sent on the legs with onset during childhood.
      Inflammatory linear verrucous epidermal nevus typically is refractory to
      treatment. Therapies range from topical treatments to lasers and surgical
      options. It is clinically and histopathologically similar to psoriasis,
      suggesting it may respond to established psoriasis treatments such as the excimer
      laser. We report the case of an otherwise healthy 20-year-old woman with dry,
      pruritic, red lesions on the right leg that had been present since infancy.
      Biopsy revealed psoriasiform hyperplasia with a verruciform surface. Multiple
      topical treatments including ablative CO2 laser therapy showed no remarkable
      improvement. The patient was then treated with a UV 308-nm excimer laser and
      showed noticeable clinical improvement. Because of its clinical and
      histopathological similarities to psoriasis, we hypothesized that the excimer
      laser may be useful in the treatment of these lesions.

PMID- 30235360
TI  - Latex hypersensitivity to injection devices for biologic therapies in psoriasis
      patients.
AB  - An allergic reaction provoked by reexposure to an allergen or antigen is known as
      a type I or immediate hypersensitivity reaction. Latex allergy is a common cause
      of type I hypersensitivity reactions. Allergic responses to latex in psoriasis
      patients receiving frequent injections with biologic agents are not commonly
      reported in the literature. We report the case of a patient with a long history
      of psoriasis who developed an allergic response after exposure to injection
      devices that contained latex components while undergoing treatment with biologic
      agents.

PMID- 30235361
TI  - Deer ked: a Lyme-carrying ectoparasite on the move.
AB  - Lipoptena cervi, known as the deer ked, is an ectoparasite of cervids
      traditionally found in northern European countries such as Norway, Sweden, and
      Finland. Although rarely reported in the United States, this vector recently has
      been shown to carry Borrelia burgdorferi and Anaplasma phagocytophylum from
      specimens collected domestically. Importantly, it has been suggested that deer
      keds are one of the many disease-carrying vectors that are now found in more
      expansive regions of the world due to climate change. We report a rare sighting
      of L cervi in Connecticut. Additionally, we captured a high-resolution photograph
      of a deer ked that can be used by dermatologists to help identify this disease
      carrying ectoparasite.

PMID- 30235362
TI  - Plantar ulcerative lichen planus: rapid improvement with a novel triple-therapy
      approach.
AB  - Ulcerative lichen planus (ULP) is a rare variant of lichen planus that is
      characterized by chronic, painful, and disabling ulcerations. Ulcerative lichen
      planus has been known to be resistant to many treatments, and therapeutic
      interventions often involve use of aggressive immunosuppressive medications
      without satisfactory remission of symptoms. We present the case of a 56-year-old
      man with an 8-year history of painful ulcerations on the right plantar foot as
      well as a large ulceration of the left lateral tongue. Biopsy confirmed a
      suspected diagnosis of plantar ULP. The patient developed marked clinical
      improvement of the cutaneous and oral mucosal lesions with oral and topical
      steroids, topical tacrolimus, and oral doxycycline after only 4 weeks of
      treatment. It is important for dermatologists to be aware of the potential
      diagnosis of plantar ULP, especially in the evaluation of chronic treatment
      resistant ulcers that often have been previously misdiagnosed. We introduce this
      novel therapeutic regimen as a rapidly effective and relatively safe alternative
      to conventional immunosuppressive agents for long-term management of plantar ULP.

PMID- 30235363
TI  - Impact of provider attire on patient satisfaction in an outpatient dermatology
      clinic.
AB  - Provider attire has been studied as a potential vector for infectious
      microorganisms in the medical setting as well as a potential factor in patient
      satisfaction. Our objective was to determine if a change from formal attire to
      fitted scrubs had a measurable impact on patient satisfaction scores in an
      outpatient dermatology setting. We designed a 2-year retrospective cohort study
      of 22 providers in an outpatient dermatology setting who transitioned from formal
      attire to fitted scrubs and had at least 12 months of patient satisfaction scores
      (measured by a third-party patient satisfaction survey) before and after the
      change in attire. The primary outcome was statistically significant change in
      patient satisfaction scores before and after the institution of fitted scrubs. A
      total of 3511 completed surveys were evaluated from the 12 months prior to the
      change in attire (study period 1), and 4191 completed surveys were evaluated in
      12 months after the change (study period 2). No significant change was seen in
      the overall survey responses. A small but statistically significant improvement
      was noted for several questions in study period 2, which suggested that a change
      from formal attire to fitted scrubs did not have a strong impact on patient
      satisfaction scores. Factors beyond provider attire likely have the greatest
      impact on patient satisfaction.

PMID- 30235364
TI  - Electronic medical records in dermatology: the good, the bad, and the ugly.

PMID- 30235365
TI  - Acute painful rash on the cheek.

PMID- 30235366
TI  - Pigmented lesion on the forearm.

PMID- 30235367
TI  - Laser scar management: focused and high-intensity medical exchange in Vietnam.
AB  - Over the last decade, the treatment of traumatic scars with lasers has emerged as
      a core component of multidisciplinary management. Military dermatologists have
      had a fundamental role in this shift by helping to develop new applications for
      existing technology and promulgate the techniques to reach additional providers
      and patients. International engagement is a prominent and highly attractive
      feature of military practice, and military dermatologists routinely participate
      in disaster response missions and ongoing planned operations. In this article,
      the author presents a military perspective on the emerging niche of trauma
      dermatology and outlines his more than 5 years of experience leveraging these
      skills to lead a multidisciplinary exchange in restorative medicine and burn scar
      management in Vietnam.

PMID- 30235368
TI  - Going digital with dermoscopy.
AB  - Digital dermoscopy refers to the acquisition and storage of digital images from a
      dermoscopic examination. In this article, we delve into the innovative world of
      digital dermoscopy with a review of its potential uses as well as some nuances of
      adapting this technology in a clinical setting, including sequential monitoring,
      teledermoscopy, and machine learning. We also discuss the acquisition and storage
      of dermoscopy images in accordance with the Health Insurance Portability and
      Accountability Act (HIPAA).

PMID- 30235369
TI  - Melasma treatment with oral tranexamic acid and a novel adjuvant topical therapy.

PMID- 30235370
TI  - Agminated heterogeneous papules on the neck.

PMID- 30235371
TI  - Friable erythema and erosions on the mouth.

PMID- 30235372
TI  - Telangiectatic patch on the neck.

PMID- 30235373
TI  - Bedside microscopy for the beginner.
AB  - Novice microscopists may struggle with identifying both the appropriate lesion
      for bedside testing as well as preparation and interpretation of the specimen.
      This article will serve as a guide to identify what type of primary lesion should
      prompt consideration of microscopic evaluation in the outpatient setting, provide
      specific details about how to properly obtain and analyze such a specimen, and
      elaborate basic information about the interpretation thereof.

PMID- 30235374
TI  - Learning curves: historical trends of FDA-reported adverse events for dermal
      fillers.
AB  - Dermal fillers are medical devices regulated by the US Food and Drug
      Administration (FDA); therefore, reported adverse events (AEs) are publicly
      available via OpenFDA. Evaluation of historical AE data trends may help
      distinguish between AEs related to expected learning curves associated with a new
      type of filler from AEs related to inherent characteristics of a product. In this
      study, the full history of AE data was evaluated to establish reproducible
      learning curves for FDA-approved dermal fillers. Reactions to AEs for new fillers
      that garner FDA approval or are awarded new indications should be in response to
      analysis of AE rate data and determination of whether they fit on a historically
      normal learning curve.

PMID- 30235375
TI  - Metastatic vulvovaginal Crohn disease in the setting of well-controlled
      intestinal disease.
AB  - The cutaneous manifestations of Crohn disease (CD) are varied and include
      pyoderma gangrenosum, erythema nodosum, and metastatic CD (MCD). The latter is
      defined as the occurrence of granulomatous lesions at a skin site distant from
      the gastrointestinal tract. Metastatic CD involving the vulva and perineum is
      rare and thus often is difficult to diagnose. It may precede, coincide with, or
      develop after the initial diagnosis of intestinal disease. A variety of clinical
      presentations have been described, including widespread nonspecific pain and
      swelling, erythematous papules and plaques, and nonhealing ulcers. The diagnosis
      often is delayed because of a low index of suspicion brought about by the rarity
      of the disease and its diverse and confusing manifestations. A skin biopsy
      usually confirms the diagnosis by revealing noncaseating granulomas in the
      dermis. Multiple oral and parenteral therapies are available, with surgical
      intervention reserved for resistant cases. We present a case of vulvovaginal MCD
      in the setting of well-controlled intestinal disease.

PMID- 30235377
TI  - Microcystic adnexal carcinoma of the external auditory canal.

PMID- 30235376
TI  - Atrophodermalike guttate morphea.

PMID- 30235378
TI  - Managing Seborrheic Keratosis: Evolving Strategies and Optimal Therapeutic
      Outcomes.
AB  - Seborrheic keratosis (SK) is the most common skin tumor seen by dermatologists in
      everyday practice. Although the lesions are mostly benign, many patients still
      elect to have asymptomatic SK removed. The historical standards of treatment are
      cryosurgery and electrocautery, two surgical options that are effective at lesion
      removal but have high rates of postoperative adverse events such as treatment
      site scarring and pigmentary alterations. The cosmetic outcomes of SK treatment
      modalities are of keen interest to dermatologists, as the American population
      becomes increasingly more diverse. In this article, the inclusion of darker
      Fitzpatrick skin types into clinical studies investigating post-treatment side
      effects of SK therapy is reviewed. The recent approval of a 40% hydrogen peroxide
      topical formulation is discussed in light of these issues, and several non
      invasive topical treatments that optimize cosmetic outcomes of SK lesion removal
      are highlighted. Finally, treatment strategies aimed at reducing cost and
      minimizing the burden of adverse sequelae are provided. J Drugs Dermatol.
      2018;17(9):933-940.

PMID- 30235379
TI  - Evaluation of Men's Trends and Experiences in Aesthetic Treatment.
AB  - Men's interest and participation in cosmetic procedures has increased in recent
      years; however, the factors that motivate or discourage men from undergoing these
      procedures is not well understood. To evaluate which factors impact men's
      decisions towards cosmetic procedures, an observational, single-site, cross
      sectional study utilizing a voluntary questionnaire was executed in a target
      population size of 209 men >=21 years old who visited the study site from 2015 to
      2017. A majority of the male respondents incorporate a basic skincare regimen
      into their daily routine (90%), have had experience with neurotoxin treatments
      (54%), and expressed interest in either neurotoxin or dermal filler treatments
      (77% and 83%, respectively). The main motivating reason to undergo a cosmetic
      procedure was pursuit of a youthful appearance and the main discouraging reasons
      were cost and time for appointments or recovery. This study suggests that a
      majority of our male patients have either embraced or are interested in cosmetic
      treatments, but the cost and time play a big role in their decision. As cosmetic
      providers, we should reflect a commitment to the male population through
      marketing efforts and offerings to increase participation in minimally invasive
      aesthetic procedures. J Drugs Dermatol. 2018;17(9):941-946.

PMID- 30235380
TI  - Rheological Properties of Several Hyaluronic Acid-Based Gels: A Comparative
      Study.
AB  - BACKGROUND: Adding lidocaine to hyaluronic acid (HA)-based gels appeared to
      modify their rheological properties, in the view of the first author. OBJECTIVE:
      This paper sought to compare the rheological properties of three CE-marked and
      FDA-approved gels, administered with and without lidocaine, along with two other
      newly FDA-approved gels. METHODS: The tested gels were as follows: NASHA(r)
      Restylane(r) with and without lidocaine; CPM(r); Belotero(r) Balance with and
      without lidocaine; 3-D Matrix(r); Surgiderm(r) 30XP (without lidocaine) and
      Juvederm(r) Ultra 3- Juvederm(r) Ultra Plus XC (with lidocaine); Preserved
      Network(r) RHA(r)2 (with lidocaine); Vycross(r) Volbella(r) (with lidocaine). For
      rheological analyses, viscoelastic data were collected with plate-plate geometry
      of 25mm, temperature regulated by a Peltier-effect plate, and the following
      assessed: Strain sweep from 0.01% to 3000% strain at 1Hz over frequency sweep
      from 0.1 to 100 Hz. RESULTS: NASHA Restylane gels with and without lidocaine
      exhibited similar viscoelastic characteristics, with very similar tan delta
      values, but the elastic modulus G' proved significantly higher when the gel was
      injected with lidocaine vs without. 3D-Matrix Surgiderm 30XP gel without
      lidocaine and Juvederm Ultra 3 with lidocaine exhibited similar viscoelastic
      characteristics, as well as tan delta values, yet the elastic modulus G' of
      Surgiderm 30XP proved significantly higher than that of Juvederm Ultra 3-Juvederm
      Ultra Plus XC. CPM Belotero Balance gels with and without lidocaine exhibited
      similar G' and G'' values. tan delta was somewhat higher when the gel was
      administered without lidocaine. VYCROSS Volbella gel exhibited a higher elastic
      modulus G' than the other Allergan gels, roughly nearing the NASHA gel values.
      Preserved Network RHA 2 gel exhibited values that were close to its partially
      cohesive "competitors", except for Vycross. CONCLUSION: Adding lidocaine to HA
      gels does modify their rheological properties yet this, to a variable extent
      depending on the product. J Drugs Dermatol. 2018;17(9):948-954.

PMID- 30235381
TI  - The Potential Role of Botulinum Toxin in Improving Superficial Cutaneous
      Scarring: A Review.
AB  - Botulinum toxins have been utilized in a number of cosmetic and therapeutic
      applications. One of the more novel uses of botulinum toxin involves its use to
      mitigate the effects of superficial cutaneous scarring. This is accomplished by
      decreasing the dynamic tension of a wound by denervating the underlying muscle.
      Studies have indicated that botulinum toxin serotypes A and B have a positive
      effect on wound healing and scar appearance. However, larger prospective,
      blinded, randomized, placebo-controlled clinical trials are required to refine
      this concept and target optimum toxin dose placement, timing, and concentration.
      The delayed onset of effect of available botulinum toxins is likely not taking
      full advantage of the scar improvement capabilities of the toxin, considering the
      time to immobilization of the muscle is a key factor in the improvement of wound
      healing with this technique. Furthermore, it has been noted in studies that the
      use of botulinum toxin can result in significant, yet temporary functional
      issues, due to prolonged paralysis of the muscle. In this paper, we review the
      role of botulinum toxin in improving scar appearance, evaluate animal and human
      studies to date demonstrating its effect on scarring, and highlight an
      opportunity for continued research in this application. J Drugs Dermatol.
      2018;17(9):956-958.

PMID- 30235382
TI  - Three-Dimensional Analysis of Minimally Invasive Vacuum-Assisted Subcision
      Treatment of Cellulite.
AB  - INTRODUCTION: This was a prospective non-randomized observational study of female
      subjects seeking treatment for cellulite who were consecutively enrolled into a
      registry. The objective was to evaluate the efficacy and safety of a tissue
      stabilized-guided subcision device for the treatment of cellulite using three
      dimensional (3D) imaging analysis. METHODS: Subjects received a single treatment
      to the buttocks and/or posterolateral thighs with the study device. Follow-up
      telephone evaluations were conducted at 3 and 14 days to evaluate safety and 30
      and 90 days to evaluate efficacy. Subjects returned to clinic at three months to
      obtain follow-up two dimensional and 3D imaging. RESULTS: Sixteen women of
      average age 44.1 years with a total of 291 lesions of cellulite were treated.
      Thirteen subjects presented for all follow up visits. Physicians graded results
      an average of 2.23/5 or "much improved" to "improved" with 9 subjects as much or
      very much improved (69.2%). Blinded assessors graded overall improvement an
      average of 2.8 (26-75% improvement) with 8 subjects having greater than 50%
      improvement overall (61.6%). Improvement in dimple depth was graded an average of
      2.9, with 9 subjects having greater than 50% improvement (69.2%). Analysis of 3D
      imaging yielded 67.4% average improvement in negative volume and 58.4%
      improvement in minimum height of dimples. Most expected treatment effects
      resolved within three months after treatment. CONCLUSION: Utilizing three
      dimensional imaging analysis, investigators quantitatively and objectively
      demonstrated efficacy of a tissue stabilized-guided subcision device in the
      treatment of cellulite of the buttocks and thighs. J Drugs Dermatol.
      2018;17(9):960-965.

PMID- 30235383
TI  - Assessing the Potential Role for Topical Melatonin in an Antiaging Skin Regimen.
AB  - BACKGROUND: Melatonin is an endogenous hormone commonly associated with
      regulation of sleep. However, over the last two decades, research has elucidated
      a range of effects associated with the compound, including anti-inflammatory,
      both direct and indirect antioxidant activity, tissue regenerative benefits, and
      preservation of mitochondrial function. Melatonin's anti-inflammatory and
      antioxidant support, coupled with its mitochondrial support, make it an
      intriguing target for use to support skin health. Human skin and hair follicles
      express functional melatonin receptors. They also engage in substantial melatonin
      synthesis. By supporting cutaneous homeostasis, melatonin and its metabolites are
      thought to attenuate carcinogenesis and possibly other pathological processes,
      including hyperproliferative/inflammatory conditions. The primary extrinsic
      driver of aging has been considered to be exposure to ultraviolet (UV) light,
      which is well-established to contribute to sunburn, immunosuppression, skin
      aging, and carcinogenesis. Topically applied melatonin has been shown to reduce
      markers of reactive oxygen species formation and to reverse signs of skin aging.
      As the global population continues to age, photo-damage remains a significant
      cutaneous concern. While use of sunscreens and UV avoidance strategies are
      essential to mitigate skin cancer risks, the potential to protect the skin and
      improve the appearance of photo-damage through the use of topical antioxidant
      support is appealing. The evidence suggests that melatonin deserves consideration
      for topical use as an anti-aging and skin protective agent. It is shown to be
      both safe and effective when topically applied. J Drugs Dermatol. 2018;17(8):966
      969.

PMID- 30235384
TI  - A Randomized, Double-Blind, Placebo-Controlled, Split-Face Study of the Efficacy
      of Topical Epidermal Growth Factor for the Treatment of Melasma.
AB  - INTRODUCTION: Melasma is a condition in which patients develop symmetric,
      reticulated, hyperpigmented macules and patches on the face which is thought to
      be the result of ultraviolet (UV) exposure and hormonal influences, although the
      pathogenesis is not completely understood. The topical application of epidermal
      growth factor has been used as a whitening agent, moisturizer, and an aid for
      wound healing. In this study, we explore the efficacy of topical EGF in the
      treatment of melasma. MATERIALS AND METHODS: This was a randomized, double-blind,
      placebo-controlled, split-face study to determine the efficacy of a topical EGF
      serum in the treatment of melasma. Fifteen women with a mean age of 44 were
      randomized to treatment side of the face and applied a topical EGF serum and a
      placebo twice daily to each designated side of the face for eight weeks. Patient
      satisfaction was assessed by use of the MelasQoL Questionnaire as well as a
      patient outcome survey. Subjects were evaluated using the Physician Global
      Aesthetic Improvement Scale (GAIS) by two board-certified dermatologists.
      RESULTS: GAIS scores showed an improvement in the melasma in 73.4% of subjects vs
      13% improvement for the placebo side. The average MelasQoL questionnaire score
      decreased from 42 to 33 with 73% of subjects having an improvement in their
      score. In addition, 73% of subjects reported an improvement in their melasma. No
      adverse events or side effects were reported with use of the topical serum or
      placebo. CONCLUSIONS: This study suggests that topical EGF is a safe,
      noninvasive, and effective treatment for melasma. J Drugs Dermatol.
      2018;17(6):970-973.

PMID- 30235385
TI  - Clinical Efficacy of a Novel Two-Part Skincare System on Pollution-Induced Skin
      Damage.
AB  - INTRODUCTION: Air pollution continues to be a global health concern and recent
      studies have shown that air pollutants can cause skin damage and skin aging
      through several pathways that induce oxidative stress, inflammation, apoptosis,
      and skin barrier dysfunction. Preventive measures need to be considered to retain
      optimal skin health, and topical skincare products may be able to alleviate the
      negative effects of air pollution on skin. A randomized, double-blind, placebo
      controlled clinical usage study was conducted to assess the efficacy and
      tolerability of a novel two-part skincare system (LVS) that was developed to
      provide protection against environmental skin aggressors including air pollution.
      After 8 weeks of use in subjects exposed to extremely high levels of pollution,
      LVS provided significant improvements compared to placebo in all clinical
      efficacy parameters including crow's feet wrinkles, overall skin damage, skin
      tone evenness, tactile roughness, and visible redness. Subject self-assessment
      questionnaires showed that the treatment product was highly rated in self
      perceived efficacy. Decreased SQOOH and MDA content in skin swab samples suggest
      that LVS helped to reduce oxidative stress in patients' skin. Histological
      analyses of biopsy samples using biomarkers related to skin structure, damage and
      function (collagen IV, MMP1, CPD, and CD1a) further support the clinical benefits
      of LVS. Altogether, the presented study is among the first to show that topical
      skincare products can help to reduce pollution-induced skin damage and improve
      skin quality, especially when specifically formulated with active ingredients
      that combat the harmful effects of air pollutants. J Drugs Dermatol.
      2018;17(9):975-981.

PMID- 30235386
TI  - Using a New Photo Scale to Compare Product Integration of Different Hyaluronan
      Based Fillers After Injection in Human Ex Vivo Skin.
AB  - BACKGROUND: The rheological properties of HA products have been investigated
      thoroughly, and these properties have been used to predict the clinical
      performance of HA fillers. It has been suggested that firm gels have a better
      ability to withstand deformation, and softer gels have been claimed to integrate
      and spread more into the tissue since they are perceived to deform more easily.
      However, the scientific published data regarding product integration of filler
      products with different physicochemical properties is limited. Thus, there is a
      need to improve the understanding regarding links between rheological properties
      of the gel material and the clinical performance. OBJECTIVE: The objectives of
      this study were: to develop and validate a photo scale for assessment of product
      distribution after intradermal injection, and to evaluate if product differences,
      such as overall rheological properties, gel particle size, swelling factor, and
      cohesivity effect the product distribution into the tissue after intradermal
      injections. MATERIAL AND METHODS: Intradermal injections of HA fillers were
      performed in ex vivo human abdominal skin samples. The skin samples were
      processed for histological evaluation. In order to evaluate the product
      integration after intradermal injection and compare the results between different
      products a 5-grade product integration scale (from 0 to 4) was developed based on
      representative microphotographs. The scale was validated and used for the
      evaluation of integration of the different products used in the study. The
      results were correlated with the rheological properties of the different
      products. RESULTS: G', the elastic modulus, is one important rheological
      parameter. Strong and firm gels have higher G' than weak and soft gels. When
      plotting the G' to mean product integration score in human skin obtained in the
      study, there was a statistically significant correlation with products with
      lowest G' having the highest integration score and products with high G' having
      the lowest integration scores. No statistical correlation could be seen when
      analyzing the score versus particle size, swelling factor, and cohesivity.
      CONCLUSION: The degree of product integration can be assessed and scored
      according to a 5-grade visual scale based on representative microphotographs.
      Products with different rheological properties distribute differently when
      injected into the skin. Firmer gel texture resulted in more targeted product
      integration whiles softer gel texture resulted in distributed product
      integration. J Drugs Dermatol. 2018;17(9):982-986.

PMID- 30235387
TI  - Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe
      Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double
      Blind Clinical Trials.
AB  - BACKGROUND: Side effects may limit the use of current tetracycline-class
      antibiotics for acne. OBJECTIVE: Evaluate the efficacy and safety of once-daily
      sarecycline, a novel, narrow-spectrum tetracycline-class antibiotic, in moderate
      to severe acne. METHODS: Patients 9-45 years with moderate to severe facial acne
      (Investigator's Global Assessment [IGA] score >= 3, 20-50 inflammatory and <= 100
      noninflammatory lesions, and <= 2 nodules) were randomized 1:1 to sarecycline 1.5
      mg/kg/day or placebo for 12 weeks in identically designed phase 3 studies (SC1401
      and SC1402). RESULTS: In SC1401 (sarecycline n=483, placebo n=485) and SC1402
      (sarecycline n=519, placebo n=515), at week 12, IGA success (>= 2-grade
      improvement and score 0 [clear] or 1 [almost clear]) rates were 21.9% and 22.6%
      (sarecycline), respectively, versus 10.5% and 15.3% (placebo; P less than 0.0001
      and P equals 0.0038). Onset of efficacy in inflammatory lesions occurred by the
      first visit (week 3), with mean percentage reduction in inflammatory lesions at
      week 12 in SC1401 and SC1402 of -51.8% and -49.9% (sarecycline), respectively,
      versus -35.1% and -35.4% (placebo; P less than 0.0001). Onset of efficacy for
      absolute reduction of noninflammatory lesion count occurred at week 6 in SC1401
      (P less than 0.05) and week 9 in SC1402 (P less than 0.01). In SC1401, the most
      common TEAEs (in >= 2% of either sarecycline or placebo group) were nausea (4.6%
      [sarecycline]; 2.5% [placebo]), nasopharyngitis (3.1%; 1.7%), headache (2.7%;
      2.7%), and vomiting (2.1%; 1.4%) and, in SC1402, nasopharyngitis (2.5%; 2.9%) and
      headache (2.9%; 4.9%). Most were not considered treatment-related. Vestibular
      (dizziness, tinnitus, vertigo) and phototoxic (sunburn, photosensitivity) TEAEs
      both occurred in <= 1% of sarecycline patients. Gastrointestinal TEAE rates for
      sarecycline were low. Among females, vulvovaginal candidiasis (SC1401: 1.1%
      [sarecycline] and 0 [placebo]; SC1402: 0.3% and 0) and mycotic infection (0.7%
      and 0; 1.0% and 0) rates were low. CONCLUSION: The narrow-spectrum antibiotic
      sarecycline was safe, well tolerated, and effective for moderate to severe acne,
      with low rates of side effects common with tetracycline antibiotics. J Drugs
      Dermatol. 2018;17(9):987-996.

PMID- 30235388
TI  - A Single Site, Open Label Clinical Trial, Evaluating the Duration, Efficacy, and
      Safety of a Novel Lip Plumper.
AB  - INTRODUCTION: Lip plumpers are topical agents that offer immediate, but
      temporary, volumization of the lips. While these products are becoming
      increasingly popular and are available at multiple retailers, there is a lack of
      clinical studies to evaluate the efficacy, longevity, and safety of the lip
      plumping products. METHODS: This is a prospective, single center, clinical trial
      to evaluate the duration, efficacy, and safety of a lip plumping agent in two
      clinical visits. Lip volume and adverse event were assessed by two clinicians at
      various time points: 15 minutes, 1 hour, 2 hours, 3 hours, and 4 hours. RESULTS:
      Twenty-two subjects were enrolled in the study, and eighteen completed the study.
      Investigator assessments of global improvement 15 minutes after application of
      the lip plumping product demonstrated improvement in lip fullness in 100% of the
      subjects (18/18), and 1 hour post-application 67% (12/18) showed an improvement
      in lip fullness that was statistically significant compared to the 2-hour
      assessment (P less than 0.05). Subject evaluations noted improvement in lip
      fullness 15 minutes post-application in 94.4% (17/18) of subjects, and 1 hour
      post-application, 89% (16/18) of the subjects who completed the trial noted some
      improvement in the volume of their lips that was statistically significant
      compared to the 2-hour post-application time point (P less than 0.0001). Subjects
      noted that they did experience a tingling and heat sensation, but a majority
      noted that that this sensation lasted less than 15 minutes. DISCUSSION: Our study
      demonstrated that the lip plumping product increased lip volume in almost all
      patients 15 minutes post-application and showed a continued improvement in lip
      fullness per investigator assessments 1 hour after application. Adverse events of
      a tingling or heat sensation were expected and observed as the topical product
      contained capsaicin, cinnamon, and menthol, all of which can induce this
      sensation by the release of substance P. J Drugs Dermatol. 2018;17(9):999-1004.

PMID- 30235389
TI  - Artificial Intelligence for the Objective Evaluation of Acne Investigator Global
      Assessment.
AB  - INTRODUCTION: The evaluation of Acne using ordinal scales reflects the clinical
      perception of severity but has shown low reproducibility both intra- and inter
      rater. In this study, we investigated if Artificial Intelligence trained on
      images of Acne patients could perform acne grading with high accuracy and
      reliabilities superior to those of expert physicians. METHODS: 479 patients with
      acne grading ranging from clear to severe and sampled from three ethnic groups
      participated in this study. Multi-polarization images of facial skin of each
      patient were acquired from five different angles using the visible spectrum. An
      Artificial Intelligence was trained using the acquired images to output
      automatically a measure of Acne severity in the 0-4 numerical range of the
      Investigator Global Assessment (IGA). RESULTS: The Artificial Intelligence
      recognized the IGA of a patient with an accuracy of 0.854 and a correlation
      between manual and automatized evaluation of r=0.958 (P less than .001).
      DISCUSSION: This is the first work where an Artificial Intelligence was able to
      directly classify acne patients according to an IGA ordinal scale with high
      accuracy, no human intervention and no need to count lesions. J Drugs Dermatol.
      2018;17(9):1006-1009.

PMID- 30235390
TI  - A Comparative Analysis of Electric and Radiofrequency Microneedling Devices on
      the Market.
AB  - Microneedling was first described in 1995 by Orentreich and Orentreich for the
      treatment of atrophic scars and wrinkles.<sup>1</sup> The local injury induced by
      dermal penetration of microneedling causes release of growth factors such as
      transforming growth factor (TGF)-alpha, TGF-beta, and platelet-derived growth
      factor (PDGF). This stimulates collagen and elastin fiber production as well as
      capillary formation, ultimately leading to tissue remodeling.<sup>2</sup>.

PMID- 30235391
TI  - Facial Volumetric Structural Rejuvenation: A Natural Approach to Restoring
      Youthfulness and Preventing Aging.
AB  - When rejuvenating the face with soft tissue fillers, one must consider its
      structural framework, and patient specific goals/needs holistically to achieve
      natural results.

PMID- 30235392
TI  - Approach to Skin Lightening in Patients With Melasma.
AB  - I read with interest the informative article by Spencer et al1 that describes the
      efficacious use as a novel skin lightening agent (LumaPro-C) for the treatment of
      patients with melasma.

PMID- 30235393
TI  - Correction: Identification of microRNA signature in different pediatric brain
      tumors.

PMID- 30235394
TI  - Phylogenetic relationships among Capuchin (Cebidae, Platyrrhini) lineages: An old
      event of sympatry explains the current distribution of Cebus and Sapajus.
AB  - Capuchin monkeys are currently represented by four species of Cebus and eight of
      Sapajus. This group is taxonomically complex and several questions still need to
      be clarified. In the current study, using mtDNA markers and a larger sample
      representation than in previous studies, we seek to understand the phylogenetic
      relationships among the capuchin lineages and their historical biogeography. All
      12 species of capuchins were analyzed for the mitochondrial Control Region and
      Cytochrome b to test two biogeographical hypotheses: "Reinvasion of the Amazon
      (ROA)" and "Sympatric Evolution (SEV)". The phylogenetic relationships among
      distinct lineages within genera is consistent with an evolutionary
      diversification pattern probably resulting from an explosive process of
      diversification and dispersal between 2.0 Ma and 3.0 Ma. Also, the analyses show
      that the ancestral capuchins were distributed in a wide area encompassing the
      Amazon and Atlantic Forest. Our results support the SEV hypothesis, showing that
      the current syntopic distribution of Cebus and Sapajus can be explained by a
      sympatric speciation event in the Amazon. We also indicate that the recently
      proposed species taxonomy of Cebus is not supported, and that S. cay and S.
      macrocephalus are a junior synonym of S. apella.

PMID- 30235395
TI  - Comparative mitogenomic analyses of Amazona parrots and Psittaciformes.
AB  - Amazon parrots are long-lived birds with highly developed cognitive skills,
      including vocal learning. Several parrot mitogenomes have been sequenced, but
      important aspects of their organization and evolution are not fully understood or
      have limited experimental support. The main aim of the present study was to
      describe the mitogenome of the blue-fronted Amazon, Amazona aestiva, and compare
      it to other mitogenomes from the genus Amazona and the order Psittaciformes. We
      observed that mitogenomes are highly conserved among Amazon parrots, and a
      detailed analysis of their duplicated control regions revealed conserved blocks.
      Population level analyses indicated that the specimen analyzed here seems to be
      close to A. aestiva individuals from Bahia state. Evolutionary relationships of
      41 Psittaciformes species and three outgroups were inferred by BEAST. All
      relationships were retrieved with high support.

PMID- 30235396
TI  - New insights into Phakopsora pachyrhizi infection based on transcriptome analysis
      in planta.
AB  - Asian soybean rust (ASR) is one of the most destructive diseases affecting
      soybeans. The causative agent of ASR, the fungus Phakopsora pachyrhizi, presents
      characteristics that make it difficult to study in vitro, limiting our knowledge
      of plant-pathogen dynamics. Therefore, this work used leaf lesion laser
      microdissection associated with deep sequencing to determine the pathogen
      transcriptome during compatible and incompatible interactions with soybean. The
      36,350 generated unisequences provided an overview of the main genes and
      biological pathways that were active in the fungus during the infection cycle. We
      also identified the most expressed transcripts, including sequences similar to
      other fungal virulence and signaling proteins. Enriched P. pachyrhizi transcripts
      in the resistant (PI561356) soybean genotype were related to extracellular matrix
      organization and metabolic signaling pathways and, among infection structures, in
      amino acid metabolism and intracellular transport. Unisequences were further
      grouped into gene families along predicted sequences from 15 other fungi and
      oomycetes, including rust fungi, allowing the identification of conserved
      multigenic families, as well as being specific to P. pachyrhizi. The results
      revealed important biological processes observed in P. pachyrhizi, contributing
      with information related to fungal biology and, consequently, a better
      understanding of ASR.

PMID- 30235397
TI  - A cytosolic class II small heat shock protein, PfHSP17.2, confers resistance to
      heat, cold, and salt stresses in transgenic Arabidopsis.
AB  - We cloned and characterized the full-length coding sequence of a small heat shock
      (sHSP) gene, PfHSP17.2, from Primula forrestii leaves following heat stress
      treatment. Homology and phylogenetic analysis suggested that PfHSP17.2 is a
      cytosolic class II sHSP, which was further supported by the cytosolic
      localization of transient expression of PfHSP17.2 fused with green fluorescent
      protein reporter. Expression analysis showed that PfHSP17.2 was highly inducible
      by heat stress in almost all the vegetative and generative tissues and was
      expressed under salt, cold, and oxidative stress conditions as well. Moreover,
      the expression of PfHSP17.2 in P. forrestii was detected in certain developmental
      growth stages. Transgenic Arabidopsis thaliana constitutively expressing
      PfHSP17.2 displayed increased thermotolerance and higher resistance to salt and
      cold compared with wild type plants. It is suggested that PfHSP17.2 plays a key
      role in heat and other abiotic stresses.

PMID- 30235398
TI  - Can WRKY transcription factors help plants to overcome environmental challenges?
AB  - WRKY transcription factors (TFs) are responsible for the regulation of genes
      responsive to many plant growth and developmental cues, as well as to biotic and
      abiotic stresses. The modulation of gene expression by WRKY proteins primarily
      occurs by DNA binding at specific cis-regulatory elements, the W-box elements,
      which are short sequences located in the promoter region of certain genes. In
      addition, their action can occur through interaction with other TFs and the
      cellular transcription machinery. The current genome sequences available reveal a
      relatively large number of WRKY genes, reaching hundreds of copies. Recently,
      functional genomics studies in model plants have enabled the identification of
      function and mechanism of action of several WRKY TFs in plants. This review
      addresses the more recent studies in plants regarding the function of WRKY TFs in
      both model and crop plants for coping with environmental challenges, including a
      wide variety of abiotic and biotic stresses.

PMID- 30235401
TI  - [Research on THz and Raman Spectra of RNA Nucleobases].
AB  - The Infrared and Raman spectra of RNA nucleobases in terahertz (THz) band (1~10
      THz) were detected with Fourier transform infrared spectroscopy (FTIR) and Raman
      spectroscopy. The position of all the characteristic peaks and corresponding
      vibration modes of RNA nucleobase crystals were obtained with Guassian09 software
      and energy-based fragmentation approach under periodic boundary conditions (PBC
      GEBF) method. The computational results were verified to be in accordance with
      experimental data, which indicated that the powder of RNA nucleobases is
      amorphous crystal structure. The infrared spectra demonstrated that adenine,
      guanine and cytosine all have 6 infrared active vibrational modes, while uracil
      only has 3. Comparing to experimental results, the position and intensity of the
      absorption peaks were nicely corroborated by the predicted spectrum, except that
      one weak vibrational frequency at 6.35 THz is missing and two peaks (4.83 and
      5.39 THz) merge in the predicted spectrum of guanine; two peaks in 4.3 and 4.79
      THz merge into a single one in the calculated spectrum of cytosine; the peaks of
      thymine in 3.32 and 3.82 THz merged. The computational results of Raman spectra
      were also verified to be in line with the experimental data. The position and
      intensity of the characteristics peaks were exactly simulated except that two
      peaks of guanine in 3.52 and 4.48 THz merged; two peaks in 7.26 and 8.03 THz
      merge and five peaks (3.57, 4.02, 4.49, 4.89, 5.98 THz) merge in the calculated
      spectrum of guanine. Through the analysis and identification of the
      characteristic peaks, it is indicated that the vibration modes of DNA nucleobases
      in 1~10 THz were derived from collective vibration of molecules in the lattice.
      The intermolecular hydrogen bond and the weak interaction force contribute
      greatly to the vibration modes. In addition, as the frequency increases to over
      5.5 THz, the vibration modes will change from the atoms collective vibration to
      some atoms vibration. This research has important theoretical and practical
      reference value to reveal the effect of RNA nucleobases in the areas of RNA
      molecular structure constitution, biological macromolecules identification and
      terahertz spectra formation mechanism and biological inheritance.

PMID- 30235400
TI  - Can plant DNA barcoding be implemented in species-rich tropical regions? A
      perspective from Sao Paulo State, Brazil.
AB  - DNA barcoding helps to identify species, especially when identification is based
      on parts of organisms or life stages such as seeds, pollen, wood, roots or
      juveniles. However, the implementation of this approach strongly depends on the
      existence of complete reference libraries of DNA sequences. If such a library is
      incomplete, DNA-based identification will be inefficient. Here, we assess if DNA
      barcoding can already be implemented in species-rich tropical regions. We focus
      on the tree flora of Sao Paulo state, Brazil, which contains more than 2000 tree
      species. Using new DNA sequence data and carefully assembled GenBank accessions,
      we assembled 12,113 sequences from ten different regions. The ITS, rbcL, psbA
      trnH, matK and trnL regions were better represented within the available
      sequences for Sao Paulo tree flora. Currently, only 58% of the Sao Paulo tree
      flora currently have at least one barcoding sequence available. However, these
      species represent on average 89% of the trees in Sao Paulo state forests.
      Therefore, conservation-oriented and ecological studies can already benefit from
      DNA barcoding to obtain more accurate species identifications. We present which
      taxa remain underrepresented for the Sao Paulo tree flora and discuss the
      implications of this result for other species-rich tropical regions.

PMID- 30235402
TI  - [Application of Terahertz Spectroscopy in the Detection of Chinese Medicine
      Processed Drugs of Rhubarb].
AB  - The changes of composition of the processed traditional Chinese medicine will
      affect the curative effect of drug, such as the four kinds of processed rhubarb.
      The characteristics data of each rhubarb was measured with terahertz spectroscopy
      system and analyzed with chemometrics, and the spectral data was classified
      according to the category of rhubarb. The substance components of anthraquinone
      and tannins make changes in processed rhubarb by thin layer chromatography (TLC).
      The correlation among the terahertz spectroscopy of processed rhubarb was in
      accordance with the variations of content. This means that terahertz spectroscopy
      is sensitive to the substance components of processed Chinese traditional
      medicine. It can also pave the way for the study of the structural changes of
      traditional Chinese medicine.

PMID- 30235399
TI  - The microbiome and inborn errors of metabolism: Why we should look carefully at
      their interplay?
AB  - Research into the influence of the microbiome on the human body has been shedding
      new light on diseases long known to be multifactorial, such as obesity, mood
      disorders, autism, and inflammatory bowel disease. Although inborn errors of
      metabolism (IEMs) are monogenic diseases, genotype alone is not enough to explain
      the wide phenotypic variability observed in patients with these conditions.
      Genetics and diet exert a strong influence on the microbiome, and diet is used
      (alone or as an adjuvant) in the treatment of many IEMs. This review will
      describe how the effects of the microbiome on the host can interfere with IEM
      phenotypes through interactions with organs such as the liver and brain, two of
      the structures most commonly affected by IEMs. The relationships between
      treatment strategies for some IEMs and the microbiome will also be addressed.
      Studies on the microbiome and its influence in individuals with IEMs are still
      incipient, but are of the utmost importance to elucidating the phenotypic variety
      observed in these conditions.

PMID- 30235403
TI  - [Comparison and Analysis of Iterative and Genetic Algorithms Used to Extract the
      Optical Parameters of Glucose Polycrystalline].
AB  - Based on the terahertz time-domain reflection spectroscopy, the optical
      parameters of anhydrous D-glucose polycrystalline, i.e. the refractive index and
      the absorption coefficient were extracted by using iterative and genetic
      algorithm, respectively. After comparing and analyzing the two algorithms we had
      drawn the following conclusions: first, the calculation efficiency of iterative
      algorithm was improved using the solution of weak absorption approximation as
      initial values. However, the iterative algorithm was sensitive to the initial
      values. When the big difference between the initial values and real values
      existed, the accuracy of optical constants would be affected; Secondly, the
      genetic algorithm was not insensitive to the initial populations. It ensured the
      convergence of the algorithm and the population diversity through the design of
      parameter coding, initial population, genetic manipulation, parameter control and
      constraint condition. Last, compared with the iterative algorithm, the optical
      parameters obtained by the genetic algorithm had higher accuracy. Therefore, we
      suggest that the optical parameters of materials with higher accuracy based on
      the THz spectroscopy can be obtained by using an intelligent optimization
      algorithm.

PMID- 30235404
TI  - [Model Optimization of Ternary System Adulteration Detection in Camellia Oil
      Based on Visible/Near Infrared Spectroscopy].
AB  - Visible/near infrared spectroscopy combined with chemometrics methods was used to
      detect ternary system adulteration in camellia oil quantificationally. In order
      to get adulterated samples, rapeseed oil and peanut oil were added to pure
      camellia oil in different proportion. Visible/near infrared spectroscopy data of
      pure and adulterated camellia oil samples were acquired in the wavelength range
      of 350~1800nm, and samples were randomly divided into calibration set and
      prediction set. The adulteration models were optimized by comparing different
      wavelength ranges, pretreatment methods and calibration methods The results show
      that the optimal modeling wavelength ranges and pretreatment methods for the
      prediction models of rapeseed oil, peanut oil and total adulteration amount are
      750~1 770, 900~1 770, 870~1 770 nm and Multiple scattering correction (MSC),
      Standard normal variate (SNV) and second order differentia, and the best modeling
      method is Least square support vector machine (LSSVM). The correlation
      coefficient (R(P)) in prediction set and the root mean square error
      predictions(RMSEPs) of optimal adulteration models for rapeseed oil, peanut oil
      and total adulteration are 0.963, 0.982, 0.993 and 2.1%, 1.5%, 1.8%,
      respectively. Thus it can be seen that visible /near infrared spectroscopy
      combined with chemometrics methods can be used for quantitative ternary system
      adulteration detection in camellia oil.

PMID- 30235405
TI  - [Research on Cloud Phase Detemination Using Infrared Emissivity Spectrum Data
      (1): Cloud Phase Determination].
AB  - As a key factor in the climate model, cloud phase is an important prerequisite to
      performing cloud property retrievals from remote sensor measurements. The ability
      to infer cloud phase using cloud emissivity spectra is investigated by numerical
      simulations. It is shown that for emissivity below 0.95, several spectral
      features such as the slopes, the ratios and the differences of the emissivity are
      consistent with the variation of cloud phase in some spectral regions.
      Specifically, these features include the slope of the cloud emissivity between
      800 and 900 cm(-1), the slope of the cloud emissivity between 900 and 1 000 cm(
      1), the difference in the mean emissivity between above-mentioned two regions,
      the ratio of the emissivity at 862.1 cm(-1) to the emissivity at 989.8 cm(-1),
      the difference in the emissivity between 862.1 and 989.8 cm(-1), the ratio of the
      emissivity at 1 900.1 cm-1 to the emissivity at 2 029.3 cm-1, the ratio of the
      mean emissivity for far-infrared region to the emissivity at 900 cm(-1). A cloud
      phase classifier is proposed based on support vector machines (SVM). A series of
      simulations including various cloud patterns are performed. The RBF kernel
      function parameters and the penalty factor of SVM are selected by using the
      genetic algorithm. The phase determination algorithm is applied for collecting
      data from the AERI at the SGP site. The results from the ground-based multisensor
      cloud phase classifier proposed by Shupe are used to validate the phase
      determination algorithm. It is found the two results are consistent in general.
      30% clouds are indicated as opaque due to its high emissivity. The cloud with
      small lidar's depolarization is misclassified as clear sky by the Shupe method.
      It can be concluded that the proposed algorithm considering the spectral
      information (spectral slopes, ratios and differences) is efficient for cloud
      phase determination of thin cloud.

PMID- 30235406
TI  - [Research on Cloud Phase Detemination Using Infrared Emissivity Spectrum Data
      (2): Retrieval of Cloud Effective Radius and Water Path].
AB  - The cloud microphysical properties such as cloud effective radius and cloud water
      path are fundamental properties for understanding the cloud formation, radiative
      impacts and interactions with aerosol and precipitation. The downwelling infrared
      radiance spectra is studied here to retrieve microphysical properties of clouds.
      The sensitivity of the downwelling radiance spectra and cloud emissivity spectra
      to the liquid cloud and ice cloud effective radius and optical depth is analyzed.
      The look-up-tables are established for optically thin clouds (cloud optical depth
      less than 6) that rely on parameters of the slopes and differences of the
      emissivity spectra. These parameters include the difference in the emissivity
      between 862.1 and 934.9 cm(-1), the difference in the emissivity between 1 900.1
      and 2 170.1 cm(-1), the slope of the cloud emissivity and the radiation between
      900 and 1 000 cm(-1), the slope of the cloud emissivity and the radiation between
      1 100 and 1 200 cm(-1). The look-up-tables are constrained by the incorporation
      of mean ozone band transmissivity between 1 050 and 1 060 cm(-1). Cloud effective
      radius and optical depth can be obtained with by least squares fitting between
      observed and modeled above-mentioned multiple spectral parameters. The cloud
      water path can then be derived from the experiential relationship. The inversion
      results are compared with the ARM baseline cloud microphysics product
      (MICROBASE). It is shown that, the cloud effective radius is roughly in the same
      order of magnitude while the water paths derived from both method are of large
      differences especially for the liquid cloud path. The algorithm proposed in this
      paper is efficient for retrieving microphysical properties of thin clouds with
      cloud optical depth less than 6.

PMID- 30235408
TI  - [Qualitative Detection of Procymidone in Edible Vegetable Oils by Near Infrared
      Spectroscopy and Variable Selection Methods].
AB  - In this research, near infrared (NIR) spectroscopy was used to detect procymidone
      in edible vegetable oils qualitatively. Edible vegetable oil samples with
      different procymidone contents were classified to two groups according to
      boundary line of maximum residue limit of procymidone in national standard.
      QualitySpec spectrometer was used to acquire spectra of two group samples, then
      uninformative variable elimination (UVE) and subwindow permutation analysis (SPA)
      were used to select informative wavelength variables. At last, several methods
      such as linear discriminant analysis (LDA), partial least squares-linear
      discriminant analysis (PLS-LDA) and discriminant partial least squares (DPLS)
      were used to develop classification models. The results indicate that NIR
      spectroscopy is feasible to classify the two group samples. UVE method can select
      informative wavelength variables effectively, and improve the performance of
      classification model. The best model is developed by UVE-DPLS method, the
      classification correct rate, sensitivity and specificity of prediction samples in
      this model are 98.7%, 95.0% and 100.0%, respectively.

PMID- 30235407
TI  - [Visible and Infrared Thermal Image Fusion Algorithm Based on Self-Adaptive
      Reference Image].
AB  - The technology of fusing visible images and infrared thermal images is one of the
      most important researching fields in terms of high-performance night vision
      technology home and abroad Using this kind of technology can efficiently improve
      people's ability of target-detecting and scene's comprehension. The commonly used
      color transfer algorithm belongs to single reference image's global color
      transfer, which results in huge influence on the color of fusion image. Thus,
      this kind of method cannot adapt to different kinds of scenes. In this essay, we
      focus on environmental adaptation problems of regular color transfer in color
      image fusion algorithm base on YUV color space. After analyzing the mean and
      standard deviation of typical scenes' UV channel, we find that it has obvious
      classified characteristics. As a result, we propose a method of constructing
      adaptive reference image based on mean and standard deviation of U and V
      channels, which makes visible and infrared thermal image fusion algorithm better
      adapt to environment and fusion images' color is natural. Furthermore, the
      handling capacity is small and it exerts little impact on the speed of algorithm
      real-time hardware processing. To conclude, it is a kind of practical natural
      color fusion processing algorithm.

PMID- 30235409
TI  - [Study of Modeling Samples Selection Method Based on Near Infrared Spectrum].
AB  - For more wheat varieties classification problem, we use near infrared spectrumto
      do qualitative analysis. Increasing the size of modeling sample could increase
      information of the model, however, at the same time, it also makes information
      redundancy so that modeling time and storage space will increase, thus, we need
      to decrease the size of modeling sample though selecting them. Some information
      must be lost and the effects of the model must be worse if we select samples
      blindly. We put forward the k nearest neighbor-density sample selection based on
      the traditional selection methods. Experiments use the near infrared diffuse
      reflection spectrum of wheat seed from lots of days. First, we use preprocessing
      and feature extraction to deal with the wheat original spectrum, then select
      modeling sample by three methods that are random sampling, k nearest neighbor and
      k nearest neighbor-density, finally, we establish the models of BPR(Biomimetic
      Pattern Recognition) and BPRI(Biomimetic Pattern Recognition Improved). The
      experimental results show that in the model of BPR we get the best results using
      the selection method of k nearest neighbor-density, especially it also decreases
      the size of modeling sample deeply, and in the model of BPRI the results using
      the selection method of k nearest neighbor-density are much better than random
      sampling and a little better than k nearest neighbor, but in the meanwhile the
      size of modeling sample using the selection method of k nearest neighbor-density
      are much smaller than k nearest neighbor. The experimental results prove that the
      sample selection method of k nearest neighbor-density can not only greatly reduce
      the modeling sample size, and ensure the quality of the model, it has obvious
      effect on varieties classification problem of wheat.

PMID- 30235410
TI  - [Characterizing Fracture Characteristics of Heterogeneous Oil and Gas Reservoir
      by Using Microscopic Infrared Spectroscopy Technique --Taking Carbonate Reservoir
      of the Wumishan Formation of Jixian System in Renqiu Burried Hill as an Example].
AB  - Oil and gas reservoir fracture is not only the important reservoir space, but
      also the main passage of the oil and gas migration. Therefore, the
      characterization of fracture is of great importance. However, reservoir rocks
      have strong heterogeneity, how to characterize heterogeneous reservoir fracture
      accurately is an urgent problem to be solved. Microscopic infrared spectroscopy
      imaging technique can be used to analyze spectral curve of the mineral molecules,
      different peak characteristics were got, and rock medium composition, the size of
      the rock fracture, and fracture filler properties and other characteristics were
      obtained accurately. In this work, carbonate heterogeneous reservoir of Renqiu
      buried hill was taken as an example, based on the microscopic infrared
      spectroscopy imaging technique, by the analysis of core sample infrared imaging
      spectrogram and spectral curves of different characteristic regions, the
      physicochemical characteristics of the target sample and spatial distribution of
      the rock medium were obtained, the regions where rock fracture maybe occurred
      were predicted and the effectiveness of the fractures was analyzed. The results
      show that the main medium of rock sample is dolomite. The rock fractures contain
      hydrocarbon organic and salt-water inclusion, which mainly exist in dolomite
      medium. The proportion of salt-water inclusion is 51.7%, and that of alkane
      organic matter is 26.0% in the fracture filler. The fracutres extend from the
      upper left region of core sample to the lower right region, which shows that the
      extended region of the core sample may be the passage of fluid migration. The
      salt-water inclusions can impede the migration of oil and gas, resulting in the
      decrease of fractures permeability. The experimental results show that the width
      of fractures is 1~1.5 mm, which belongs to large fracture, oil and gas can pass
      the fractures smoothly, therefore, the effectiveness of the fracture is good. The
      results showed that it is feasible to characterize the fracture of heterogeneous
      reservoir by means of microscopic infrared spectroscopy imaging technique, and it
      provides a new method for the accurate characterization of the fracture of
      heterogeneous reservoir.

PMID- 30235411
TI  - [Wavelength Variable Selection Method in Near Infrared Spectroscopy Based on
      Discrete Firefly Algorithm].
AB  - Taking into consideration of the large size of near-infrared spectral data, the
      spectral data has to be compressed to reduce the computational complexity of the
      established spectral calibration model and improve accuracy and robustness of the
      model. Near Infrared Spectroscopy wavelength variable selection method based on
      discrete firefly algorithm is presented. First, the Monte Carlo method was used
      to exclude outliers, and Kennard-Stone method was chosen for the selection of
      calibration set and prediction set. General firefly algorithm was discretized, by
      improving the attractiveness of adaptive formula, increasing traction weights in
      mobile formula and so on. In order to adapt to the effects of discretization and
      optimize algorithm, elitist strategy was added in the discrete firefly algorithm,
      to accelerate the convergence rate. The optimum value of the DFA algorithm
      parameters was found in the experiment. With wavelength variables selection based
      on discrete firefly algorithm, succinic acid concentration of the fermentation
      broth partial least squares NIR calibration model was built, which was compared
      with genetic algorithm method. The results showed that the correlation
      coefficient of calibration set (R2c) of PLS calibration model based on discrete
      wavelengths firefly algorithm is 0.986, RMSEC of which is 0.409. Correlation
      coefficient of prediction set (R2p) is 0.969 while RMSEP is 0.458. It is superior
      to full spectrum modeling and calibration model using genetic algorithm method.
      DFA shows superiority of the near-infrared spectral data filtering.

PMID- 30235412
TI  - [Quantitive Analysis of Contents in Yogurt and Application Research with FTIR
      Spectroscopy].
AB  - Yogurt is a food produced by bacterial fermentation of milk. All kinds of
      nutrition components are changing dramatically in the process of fermentation.
      Therefore, it is important to establish a fast and efficient measurement
      technology of yogurt nutrition, which is also an important goal for food safety
      supervision in terms of monitoring the yogurt production process in real time.
      Fourier transform infrared spectroscopy (FTIR) has been widely used in the field
      of food safety, for it has high efficiency, high throughput, no chemical
      pollution, thus it can be used in the inspection of food adulteration. Our study
      has established a quantitative model to predict the nutrition components in
      yogurt, such as energy value, protein, fat, carbohydrates and sodium content.
      Based on the least squares (PLS) method, the model used CaF(2) film FTIR
      technology. The results show that the new model can be used in quality control of
      yogurt production process: The R(2) values of the model were 0.938 9, 0.926 6,
      0.918 6,  0.941 8 and 0.977 1, comparing energetic value, protein, fat,
      carbohydrate and sodium contents with the original spectrum of calibration
      samples by cross validation. And the predictive R(2) are 0.920 5, 0.905 3, 0.908
      5, 0.939 3 and 0.936 4 respectively. Thus, the model has good prediction accuracy
      and reliability, which provides a feasible method for the rapid measurement of
      yogurt quality. As a preliminary exploration of the quality control technology of
      dairy products, this method has a good prospect of application.

PMID- 30235413
TI  - Using Bulk-like Nanocrystals To Probe Intrinsic Optical Gain Characteristics of
      Inorganic Lead Halide Perovskites.
AB  - Following the introduction of perovskites for photovoltaic solar energy
      conversion, the use of these materials as a general purpose optoelectronic
      material for displays, lighting, and lasing has been explored. However, while
      reports on stimulated emission and lasing by perovskites show great promise, a
      comprehensive quantification of their optical gain characteristics is lacking.
      Here, we measure gain coefficients, clarify the gain mechanism, and explore the
      gain dynamics of colloidal CsPbBr3 nanocrystals by deploying a unique combination
      of broadband transient absorption and ultrafast fluorescence spectroscopy.
      Opposite from current literature, we show that optical gain in such nanocrystals
      is supported by stimulated emission from free carriers, and not from excitons or
      biexcitons. Importantly, we demonstrate that the concomitant gain coefficients
      and thresholds agree with literature results reported for perovksite thin films.
      Finally, we show that, even in the case of fully inorganic lead halide
      perovskites, a cooling bottleneck hampers the development of net stimulated
      emission at high excitation density. Based on these results, we propose that bulk
      like colloidal nanocrystals in general offer a unique testbed to quantify optical
      gain of novel photonic materials and in particular for lead halide perovskites.

PMID- 30235415
TI  - Protein Electronics: Chemical Modulation of Contacts Control Energy Level
      Alignment in Gold-Azurin-Gold Junctions.
AB  - Making biomolecular electronics a reality will require control over charge
      transport across biomolecules. Here we show that chemical modulation of the
      coupling between one of the electronic contacts and the biomolecules in a solid
      state junction allows controlling electron transport (ETp) across the junction.
      Employing the protein azurin (Az), we achieve such modulation as follows: Az is
      covalently bound by Au-S bonding to a lithographically prepared Au electrode (Au
      Az). Au nanowires (AuNW) onto which linker molecules, with free carboxylic group,
      are bound via Au-S bonds serve as top electrode. Current-voltage plots of AuNW
      linkerCOOH//Az-Au junctions have been shown earlier to exhibit step-like
      features, due to resonant tunneling through discrete Az energy levels. Forming an
      amide bond between the free carboxylic group of the AuNW-bound linker and Az
      yields AuNW-linkerCO-NH-Az-Au junctions. This Az-linker bond switches the ETp
      mechanism from resonant to off-resonant tunneling. By varying the extent of this
      amide bonding, the current-voltage dependence can be controlled between these two
      mechanisms, thus providing a platform for altering and controlling the ETp
      mechanism purely by chemical modification in a two-terminal device, i.e., without
      a gate electrode. Using results from conductance, including the energy barrier
      and electrode-molecule coupling parameters extracted from current-voltage fitting
      and normalized differential conductance analysis and from inelastic-electron
      tunneling and photoelectron spectroscopies, we determine the Az frontier orbital
      energies, with respect to the Au Fermi level, for four junction configurations,
      differing only in electrode-protein coupling. Our approach and findings open the
      way to both qualitative and quantitative control of biomolecular electronic
      junctions.

PMID- 30235414
TI  - Synthetic Lateral Metal-Semiconductor Heterostructures of Transition Metal
      Disulfides.
AB  - Lateral heterostructures with planar integrity form the basis of two-dimensional
      (2D) electronics and optoelectronics. Here we report that, through a two-step
      chemical vapor deposition (CVD) process, high-quality lateral heterostructures
      can be constructed between metallic and semiconducting transition metal disulfide
      (TMD) layers. Instead of edge epitaxy, polycrystalline monolayer MoS2 in such
      junctions was revealed to nucleate from the vertices of multilayered VS2
      crystals, creating one-dimensional junctions with ultralow contact resistance
      (0.5 kOmega.MUm). This lateral contact contributes to 6-fold improved field
      effect mobility for monolayer MoS2, compared to the conventional on-top nickel
      contacts. The all-CVD strategy presented here hence opens up a new avenue for all
      2D-based synthetic electronics.

PMID- 30235416
TI  - Self-Prevention of Well-Defined-Facet Fe2O3/MoO3 against Deposition of Ammonium
      Bisulfate in Low-Temperature NH3-SCR.
AB  - Low-temperature selective catalytic reduction of NO by NH3 (NH3-SCR) is a
      promising technology for controlling NO emission from various industrial boilers,
      but it remains challenging because unavoidable deposition of ammonium bisulfates
      (ABS) in the stack gases containing both SO2 and H2O inevitably results in
      deactivation of catalysts. Here we developed a stable low-temperature NH3-SCR
      catalyst by supporting Fe2O3 cubes on surfaces of MoO3 nanobelts with NH4+
      intercalatable interlayers, which enables Fe2O3/MoO3 to spontaneously prevent ABS
      from depositing on the surfaces. Using in situ synchrotron X-ray diffraction, 1H
      magic angle spinning nuclear magnetic resonance, and temperature-programmed
      decomposition procedure, the results demonstrate that NH4+ of ABS was initially
      intercalated in the interlayers of MoO3, leading to a NH4+-HSO4- cation-anion
      separation by conquering their strong electrostatic interactions, and
      subsequently the separated NH4+ was consumed by taking part in low-temperature
      NH3-SCR. Meanwhile, the surface HSO4- separated from ABS oxidized the reduced
      catalyst during the NH3-SCR redox cycle, concomitant with release of SO2 gas,
      thereby resulting in decomposition of ABS. This work assists the design of stable
      low-temperature NH3-SCR catalysts with strong resistance against deposition of
      ABS.

PMID- 30235418
TI  - Base-Catalyzed Transesterification of Thionoesters.
AB  - Here we report a convenient synthesis of thionoesters by base-catalyzed
      transesterification. Benzyl and alkyl thionobenzoates and thionoheterobenzoates
      were efficiently prepared using various alcohols catalyzed by the corresponding
      sodium alkoxide. This methodology features a broad substrate scope, good to
      excellent yields, short reaction times, while simultaneously driving the reaction
      toward completion through the removal of the methanol byproduct. We also report
      the conversion of a small collection of thionobenzoates into the corresponding
      alpha,alpha-difluorobenzyl ethers to demonstrate the conversion of alcohols into
      difluorobenzyl or difluoroheterobenzyl ethers, a process that could prove useful
      for lead optimization in medicinal chemistry.

PMID- 30235417
TI  - Interplay of Surface Recombination and Diode Geometry for the Performance of
      Axial p-i-n Nanowire Solar Cells.
AB  - Nanowires (NWs) with axial p-i-n junctions have been widely explored as
      microscopic diodes for optoelectronic and solar energy applications, and their
      performance is strongly influenced by charge recombination at the surface. We
      delineate how the photovoltaic performance of these diodes is dictated not only
      by the surface but also by the complex and seemingly counterintuitive interplay
      of diode geometry, that is, radius ( R) and intrinsic length ( Li), with the
      surface recombination velocity ( S). An analytical model to describe these
      relationships is developed and compared to finite-element simulations, which
      verify the accuracy and limitations of the model. The dependence of the dark
      saturation current ( I0), internal quantum efficiency (IQE), short-circuit
      current ( ISC), and open-circuit voltage ( VOC) on both geometric and
      recombination parameters demonstrates that no single set of parameters produces
      optimal performance; instead, various trade-offs in performance are observed. For
      instance, longer Li might be expected to produce higher ISC, yet at high values
      of S the ISC declines because of decreases in IQE. Moreover, longer Li produces a
      concurrent decline in VOC regardless of S due to increases in I0. We also find
      that ISC and VOC trends are radius independent, yet I0 is directly proportional
      to R, causing NWs with smaller R to display higher turn-on voltages. The analysis
      regarding the interplay of these parameters, verified by experimental
      measurements with various p-i-n geometries and surface treatments, provides clear
      guidance for the rational design of performance metrics for photodiode and
      photovoltaic devices.

PMID- 30235419
TI  - Medical Scribes: The Future for Medical Data Input in Emergency Departments.
AB  - Despite their widespread use, electronic medical records have created
      frustrations for physicians, especially those working in busy hospital emergency
      departments. After a brief discussion of the causes of the problems, a potential
      solution-the use of medical scribes-is presented. The extant literature regarding
      results obtained following the implementation of medical scribes in emergency
      departments is reviewed and some conclusions regarding the future of this
      phenomenon are presented. The future looks quite bright for use of medical
      scribes in hospitals' emergency departments.

PMID- 30235420
TI  - Active Travel for All? The Surge in Public Bike-Sharing Programs.

PMID- 30235421
TI  - A National Multicity Analysis of the Causal Effect of Local Pollution, [Formula:
      see text], and [Formula: see text] on Mortality.
AB  - BACKGROUND: Studies have long associated [Formula: see text] with daily
      mortality, but few applied causal-modeling methods, or at low exposures. Short
      term exposure to [Formula: see text], a marker of local traffic, has also been
      associated with mortality but is less studied. We previously found a causal
      effect between local air pollution and mortality in Boston. OBJECTIVES: We aimed
      to estimate the causal effects of local pollution, [Formula: see text], and
      [Formula: see text] on mortality in 135 U.S. cities. METHODS: We used three
      methods which, under different assumptions, provide causal marginal estimates of
      effect: a marginal structural model, an instrumental variable analysis, and a
      negative exposure control. The instrumental approach used planetary boundary
      layer, wind speed, and air pressure as instruments for concentrations of local
      pollutants; the marginal structural model separated the effects of [Formula: see
      text] from the effects of [Formula: see text], and the negative exposure control
      provided protection against unmeasured confounders. RESULTS: In 7.3 million
      deaths, the instrumental approach estimated that mortality increased 1.5% [95%
      confidence interval (CI): 1.1%, 2.0%] per [Formula: see text] increase in local
      pollution indexed as [Formula: see text]. The negative control exposure was not
      associated with mortality. Restricting our analysis to days with [Formula: see
      text] below [Formula: see text], we found a 1.70% (95% CI 1.11%, 2.29%) increase.
      With marginal structural models, we found positive significant increases in
      deaths with both [Formula: see text] and [Formula: see text]. On days with
      [Formula: see text] below [Formula: see text], we found a 0.83% (95% CI 0.39%,
      1.27%) increase. Including negative exposure controls changed estimates
      minimally. CONCLUSIONS: Causal-modeling techniques, each subject to different
      assumptions, demonstrated causal effects of locally generated pollutants on daily
      deaths with effects at concentrations below the current EPA daily [Formula: see
      text] standard. https://doi.org/10.1289/EHP2732.

PMID- 30235422
TI  - Rapid travel to a Zika vaccine: are we heading towards success or more questions?
AB  - INTRODUCTION: The emergence of the Zika virus (ZIKV) in Latin America in 2015
      2016 led to an expeditious search for vaccine candidates, with a DNA-based
      candidate having progressed to Phase II. However, several features of ZIKV
      infection and epidemiology are not understood, which may be key to maximizing
      efficacy and ensuring safety of ZIKV vaccines. Areas covered: Conceivable
      problems related to vaccine development and policy include: (1) paucity of
      diagnostics to satisfactorily discriminate between past ZIKV and dengue virus
      (DENV) exposure; (2) insufficient knowledge of the mechanisms of ZIKV
      neurovirulence, amongst other unknowns in the biology of this infection, is
      particularly relevant from a vaccine safety perspective; and (3) the potential
      for disease enhancement, as observed with DENV infection and vaccine. Expert
      opinion: Vaccine candidates that entered phase I/II trials have demonstrated
      protection in naive animal models, while ZIKV epidemics occurred in populations
      that had encountered DENV before. The resulting cross-reactive antibodies pose
      problems for reliable serologic diagnostic assays, and for the potential of
      disease enhancement. The alleged neurological complications also warrant further
      exploration in order to reassure regulators of the safety profile of these
      vaccines in target populations. These research aspects should be an integral part
      of the efforts to develop a vaccine.

PMID- 30235425
TI  - Dr David Donaldson, BDS, FDSRCS, MDS, FADSA, FAAD, Dental Educator and Sedation
      Pioneer, Dies at 76.

PMID- 30235423
TI  - Zurich Statement on Future Actions on Per- and Polyfluoroalkyl Substances
      (PFASs).
AB  - Per- and polyfluoroalkyl substances (PFASs) are man-made chemicals that contain
      at least one perfluoroalkyl moiety, [Formula: see text]. To date, over 4,000
      unique PFASs have been used in technical applications and consumer products, and
      some of them have been detected globally in human and wildlife biomonitoring
      studies. Because of their extraordinary persistence, human and environmental
      exposure to PFASs will be a long-term source of concern. Some PFASs such as
      perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) have been
      investigated extensively and thus regulated, but for many other PFASs, knowledge
      about their current uses and hazards is still very limited or missing entirely.
      To address this problem and prepare an action plan for the assessment and
      management of PFASs in the coming years, a group of more than 50 international
      scientists and regulators held a two-day workshop in November, 2017. The group
      identified both the respective needs of and common goals shared by the scientific
      and the policy communities, made recommendations for cooperative actions, and
      outlined how the science-policy interface regarding PFASs can be strengthened
      using new approaches for assessing and managing highly persistent chemicals such
      as PFASs. https://doi.org/10.1289/EHP4158.

PMID- 30235426
TI  - Atrio-ventricular Block Following Neostigmine-Glycopyrrolate Reversal in Non
      heart Transplant Patients: Case Report.
AB  - Neostigmine is the anticholinesterase drug most commonly used to reverse blockade
      or speed up recovery from neuromuscular blockade from nondepolarizing
      neuromuscular blocking drugs. Because of its cardiac muscarinic effects, prior or
      simultaneous administration of glycopyrrolate or atropine is usually recommended.
      There have been a few case reports of bradycardia, atrio-ventricular (AV) block,
      and cardiac arrest following neostigmine/glycopyrrolate administration to reverse
      neuromuscular block affecting several patients. In this report, we describe a
      case of 21-year-old with a history of seizure disorder and developmental delay
      that presented for dental surgery under general anesthesia and developed type I
      AV block following the simultaneous administration of neostigmine and
      glycopyrrolate to reverse a nondepolarizing neuromuscular block with rocuronium
      at the end of his surgery. We suggest that the chronic use of antiepileptic drugs
      in this patient in combination with neostigmine and glycopyrrolate lead to AV
      block in this patient. We also review similar cases reported in the literature
      and suggest an explanation for this observed phenomenon.

PMID- 30235424
TI  - Opportunities and Challenges for Dietary Arsenic Intervention.
AB  - The diet is emerging as the dominant source of arsenic exposure for most of the
      U.S. population. Despite this, limited regulatory efforts have been aimed at
      mitigating exposure, and the role of diet in arsenic exposure and disease
      processes remains understudied. In this brief, we discuss the evidence linking
      dietary arsenic intake to human disease and discuss challenges associated with
      exposure characterization and efforts to quantify risks. In light of these
      challenges, and in recognition of the potential longer-term process of
      establishing regulation, we introduce a framework for shorter-term interventions
      that employs a field-to-plate food supply chain model to identify monitoring,
      intervention, and communication opportunities as part of a multisector,
      multiagency, science-informed, public health systems approach to mitigation of
      dietary arsenic exposure. Such an approach is dependent on coordination across
      commodity producers, the food industry, nongovernmental organizations, health
      professionals, researchers, and the regulatory community.
      https://doi.org/10.1289/EHP3997.

PMID- 30235428
TI  - Comparison of the Contact Force Exerted on Teeth by Conventional Macintosh
      Laryngoscope Versus Video Laryngoscopes.
AB  - During laryngoscopy, the laryngoscope blade sometimes comes in contact with the
      teeth, fracturing or dislocating them. However, no studies have compared the
      effects of newly marketed video laryngoscopes and the Macintosh laryngoscope
      (Mac) on teeth. In this study, we measured and compared the force exerted on the
      teeth of an intubating manikin by the Mac, the Airway Scope (Pentax), and the
      McGrath MAC (Covidien). The mean force exerted was 141.1 +/- 15.7 kg by the Mac,
      39.2 +/- 10.3 kg by the Airway Scope, and 48.7 +/- 6.7 kg by the McGrath MAC. No
      significant difference was observed between the Airway Scope and the McGrath MAC.
      When the Mac is inserted, the glottis has to be visually located from outside the
      oral cavity. However, a significant force is not necessary when inserting video
      laryngoscopes because a camera is mounted on the blade tip. In this laboratory
      model, the lower force exerted by the video laryngoscopes should contribute to a
      reduction in their impact on fracture or dislocation of teeth.

PMID- 30235427
TI  - The Effect of Dexmedetomidine on Oral Mucosal Blood Flow and the Absorption of
      Lidocaine.
AB  - Dexmedetomidine (DEX) is a sedative and analgesic agent that acts via the alpha-2
      adrenoreceptor and is associated with reduced anesthetic requirements, as well as
      attenuated blood pressure and heart rate in response to stressful events. A
      previous study reported that cat gingival blood flow was controlled via
      sympathetic alpha-adrenergic fibers involved in vasoconstriction. In the present
      study, experiment 1 focused on the relationship between the effects of DEX on
      alpha adrenoreceptors and vasoconstriction in the tissues of the oral cavity and
      compared the palatal mucosal blood flow (PMBF) in rabbits between general
      anesthesia with sevoflurane and sedation with DEX. We found that the PMBF was
      decreased by DEX presumably because of the vasoconstriction of oral mucosal
      vessels following alpha-2 adrenoreceptor stimulation by DEX. To assess if this
      vasoconstriction would allow decreased use of locally administered epinephrine
      during DEX infusion, experiment 2 in the present study monitored the serum
      lidocaine concentration in rabbits to compare the absorption of lidocaine without
      epinephrine during general anesthesia with sevoflurane and sedation with DEX. The
      depression of PMBF by DEX did not affect the absorption of lidocaine. We
      hypothesize that this is because lidocaine dilates the blood vessels,
      counteracting the effects of DEX. In conclusion, despite decreased palatal blood
      flow with DEX infusion, local anesthetics with vasoconstrictors should be used in
      implant and oral surgery even with administered DEX.

PMID- 30235429
TI  - General Anesthetic Management of a Patient With Hypertrophic Cardiomyopathy for
      Oral Surgery: Did Digitalis Contribute to Bradycardia?
AB  - Stabilization of circulatory dynamics is a critical issue in the anesthetic
      management of patients with hypertrophic cardiomyopathy (HCM). In this report, we
      managed general anesthesia for a 74-year-old male patient with nonobstructive HCM
      who developed circulatory instability intraoperatively. Severe bradycardia
      measuring 35 beats/min and hypotension measuring 78 mm Hg systolic were observed
      during surgery. Using stroke volume variation and stroke volume from the FloTrac
      as indices, successful circulatory management was performed with dopamine. The
      hypotension and bradycardia were thought to be the result of methyldigoxin and
      possibly associated with our perioperative management. Cardiology consult should
      have been obtained. We demonstrated that the FloTrac can be beneficial in
      diagnosing and managing cardiovascular instability and administration of dopamine
      in the anesthetic management of nonobstructive HCM patients.

PMID- 30235430
TI  - Anesthetic Management of the Hypertensive Patient: Part II.
AB  - Hypertension is an important health challenge that affects millions of people
      across the world today and is a major risk factor for cardiovascular disease. It
      is critical that anesthesia providers have a working knowledge of the systemic
      implications of hypertension. This review article will discuss the medical
      definitions of hypertension, the physiology of maintaining blood pressure,
      outpatient treatment of hypertension, anesthetic implications, and the common
      medications used by anesthesia providers in the treatment of hypertension. Part I
      provided an overview of hypertension and blood pressure regulation. In addition,
      drugs predominantly affecting control of hypertension via renal mechanisms such
      as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor
      blockers, and renin-inhibiting agents were discussed. In part II, the remaining
      major antihypertensive medications will be reviewed as well as anesthetic
      implications of managing patients with hypertension.

PMID- 30235431
TI  - Comparison of Risk Factors in Patients With Acute and Chronic Orofacial Pain.
AB  - Management of patients with orofacial pain may benefit from a better
      understanding about patient factors that may lead pain chronicity. In this study,
      we retrospectively compared physical and psychological factors in patients with
      acute and chronic orofacial pain. We analyzed data from 854 patients presenting
      to the Orofacial Pain Center, Department of Dental Anesthesiology, Tokyo Dental
      College, Suidobashi Hospital between April 2010 and March 2014. We categorized
      patients into the acute group if their condition had persisted <6 months and the
      chronic group if their condition had lasted 6 months or longer, based on the
      classification by the International Association for the Study of Pain. The
      retrospective data were analyzed by using univariate analysis on background
      factors from a health questionnaire, pain evaluation sheet, and psychological
      test completed at the time of presentation. Multiple logistic regression was
      applied on these factors. Our results suggest that female gender and high trait
      anxiety may be involved in orofacial pain becoming chronic.

PMID- 30235432
TI  - American Society of Dentist Anesthesiologists: Parameters of Care.

PMID- 30235433
TI  - When Can the Recovery Process Be Delegated to Staff?

PMID- 30235434
TI  - Male Gender and High Trait Anxiety Are 2 Major Factors Associated With Severe
      Dental Fear and Avoidance.
AB  - The purpose of this article is to investigate the association between the
      background characteristics of patients with severe fear of dental treatment who
      frequently avoid dental care and the degree of difficulty in treating them. At
      the time of initial presentation at a dental phobia clinic, each of 321 subjects
      was asked to complete the State-Trait Anxiety Inventory, the Dental Anxiety
      Scale, and a health questionnaire related to phobic objects. Subjects who
      rejected oral examination with a dental mirror were categorized as being severely
      difficult to treat, whereas those who were able to undergo examination were
      categorized as being moderately difficult to treat. In the statistical analysis,
      assessment items that were correlated with difficulty to treat were designated as
      independent variables for a logistic regression analysis. In the logistic
      regression analysis, significant correlations were observed for gender (male >
      female with adjusted odds ratio, 4.121; 95% CI, 1.96-8.65) and level of trait
      anxiety (2.401; 1.01-5.73). Male gender and a high trait anxiety were identified
      as major factors associated with severe dental fear and avoidance.

PMID- 30235435
TI  - A Review of Current Literature of Interest to the Office-Based Anesthesiologist.

PMID- 30235436
TI  - Office-Based Anesthetic and Oral Surgical Management of a Child With Hereditary
      Sensory Autonomic Neuropathy Type IV: A Case Report.
AB  - Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital
      insensitivity to pain with anhidrosis, is an exceptionally rare genetic disorder
      that results in the complete loss of pain and temperature sensation as well as
      anhidrosis. Anesthetic management of these patients can be difficult because of
      significantly increased risks during general anesthesia. Literature on
      perioperative anesthetic management is typically written in the context of a
      hospital setting. As such, our case presents a unique report on the anesthetic
      management of a HSAN IV patient who presented for extraction of 2 teeth in an
      office-based setting. In determining how to safely manage the procedure, we
      decided against general anesthesia as we lacked the facilities and equipment to
      safely handle previously reported complications. We were successful in providing
      sedation with nitrous oxide in oxygen and applying 20% benzocaine topical
      ointment on the surgical site in lieu of administering general anesthesia. We had
      an anesthesiologist present and obtained intravenous access prior to the surgery
      to help manage any complications. This report provides support that simple dental
      extractions can be accomplished safely in the HSAN IV patient in the office-based
      setting, thereby avoiding unnecessary risk.

PMID- 30235437
TI  - Effect of Nitrous Oxide on Pulpal Anesthesia: A Preliminary Study.
AB  - To compare the success of perceived pulpal anesthesia between groups using
      nitrous oxide/oxygen (N2O/O2) and oxygen (O2) in children premedicated with
      ibuprofen with symptomatic irreversible pulpitis permanent teeth. Thirty-three
      children (mean age 10.4 +/- 1.9 years) with 33 symptomatic irreversible pulpitis
      permanent teeth were included in this preliminary study. All children were
      premedicated with ibuprofen and randomly assigned to receive either N2O/O2 (17
      participants) or O2 (16 participants). Four percent articaine with epinephrine
      1:100,000 was administered, and vital pulp therapy was performed. Children used
      the Wong-Baker FACES Pain Rating Scale (WBFPS) to report their pain at baseline
      as well as during carious dentin removal, pulpal exposure, and pulpal tissue
      removal steps. The success was determined when the reported WBFPS score was <=4.
      The chi-square test was used to compare the success between both groups. The
      success of pulpal anesthesia was 71% (12/17) and 19% (3/16) in the N2O/O2 and O2
      groups, respectively. The success in the N2O/O2 group was 52% higher than that in
      the O2 group (confidence interval = 22.9% to 80.7%; significant difference p =
      .003). From the result of this preliminary study, N2O/O2 significantly increased
      the success of perceived pulpal anesthesia in children premedicated with
      ibuprofen with symptomatic irreversible pulpitis permanent teeth. However,
      further study with a larger sample is required to confirm this result.

PMID- 30235438
TI  - AirWay ScopeTM for Difficult Ventilation in a Patient With Epiglottic Cyst.
AB  - Epiglottic cysts often cause difficulty in airway management, with potential
      serious life-threatening complications. 1 This case report describes a patient
      with an epiglottic cyst in whom mask ventilation became difficult after induction
      of anesthesia. Immediately, an AirWay ScopeTM (TMAWS-S100; Pentax, Japan) was
      inserted orally, and the location of the epiglottis was clarified to assess the
      reason for difficulty with ventilation. This case demonstrates usefulness of the
      AirWay Scope in patients with epiglottic cyst.

PMID- 30235439
TI  - Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases
      Extracellular Matrix-Associated Protein Expression.
AB  - BACKGROUND/AIMS: Uterine leiomyomas (ULs) are benign uterine tumors, and the most
      notable pathophysiologic feature of ULs is excessive accumulation of
      extracellular matrix (ECM). Fucoidan is a polysaccharide extracted from brown
      seaweeds that has a wide range of pharmacological properties, including anti
      fibrotic effects. We aimed to study the effect of fucoidan on the growth of ULs
      activated by transforming growth factor beta (TGFbeta). METHODS: We used ELT-3
      (Eker rat leiomyoma tumor-derived cells) and HUtSMC (human uterine smooth muscle
      cells) as in vitro models. Cell viability was determined by the MTT assay. Cell
      colony formation was stained using crystal violet. The side population, cell
      cycle and apoptosis were analyzed using flow cytometry. Protein expression was
      assayed by western blot analysis. We also conducted in vivo experiments to
      confirm the inhibitory effects of fucoidan in nude mouse xenograft models. Tumor
      tissues were assayed by immunohistochemistry analysis. RESULTS: In our study,
      fucoidan caused a 50% growth inhibition using a dose of 0.5 mg/ml and decreased
      the stem cell activity after 48 h. In addition, fucoidan induced sub-G1 cell
      cycle arrest and apoptosis. Fucoidan down-regulated fibronectin, vimentin, alpha
      SMA and the COL1A1 protein levels in TGFbeta3-induced ELT-3 cells. In the
      cellular mechanism, fucoidan abrogated TGFbeta3-induced levels of p-Smad2 and p
      ERK1/2, as well as beta-catenin translocation into the nucleus. Furthermore,
      fucoidan suppressed xenograft tumor growth in vivo. CONCLUSION: Fucoidan displays
      anti-proliferation and anti-fibrotic effects and exerts protective effects
      against ULs development.

PMID- 30235441
TI  - Cardiac Troponin T Risk Stratification Model Predicts All-Cause Mortality
      Following Kidney Transplant.
AB  - BACKGROUND: We evaluated the role of increased cardiac troponin T (cTnT),
      vascular, and cardiac diseases in predicting 5 and 10-year all-cause mortality
      after kidney transplantation. METHODS: We reviewed a cohort of 764 kidney
      transplant recipients and analyzed pertinent cardiovascular risk factors at the
      time of transplant evaluation. Proportional hazards regression analysis with
      bootstrapping method was utilized to provide a risk stratification score for
      mortality. RESULTS: Mean age was 58.8 years (SD 12.1) and median follow-up was
      7.0 years (range 1 day to 18.0 years). Fifty-four percent of patients (n = 415)
      had cTnT measured (median 0.02 ng/mL, range 0.01-4.91). Fifty-three percent (n =
      407) had vascular disease, 59% (n = 448) had diabetes, and 44% (n = 336) had
      cardiac disease pre-transplant. Sixty percent (n = 460) required dialysis. Older
      age, increased cTnT, pre-transplant vascular and cardiac diseases predicted
      mortality in multivariate analysis. We derived 2 scoring systems with and without
      cTnT - the ACV and ACTV scores (age, cardiac disease, elevated cTnT, and vascular
      disease) - as predictors of mortality after kidney transplant. Point assignments
      were: age 60-69 years (1), age >=70 years (2), cardiac disease (1), cTnT >=0.04
      ng/mL (1), and vascular disease (1). Both scoring systems significantly predicted
      mortality. The ACTV score better delineated risk stratification across score
      levels (0-2, 3-4, and 5 points). CONCLUSIONS: We developed a risk schema
      predictive of all-cause mortality after kidney transplant in a derivation cohort.
      The ACTV score, including an elevated cTnT, provided superior prediction compared
      to a scoring system without cTnT. Further studies to validate these findings are
      needed.

PMID- 30235440
TI  - Insulin Resistance Index from Oral Glucose Tolerance Test Predicts Ischemic
      Stroke Outcomes in Non-Diabetic Patients with Different Estimated Glomerular
      Filtration Rate Strata.
AB  - BACKGROUND: Insulin resistance is associated with cardiovascular morbidity and
      mortality in the general population. However, the relationship between insulin
      resistance and health outcomes is controversial in patients with impaired renal
      function. Our study aimed to investigate the association between insulin
      resistance and prognosis in a cohort of non-diabetic stroke patients with
      different estimated glomerular filtration rate (eGFR) strata. METHODS: Data were
      derived from Abnormal Glucose Regulation in Patients with Acute Stroke across
      China (ACROSS-China) registry. Ischemic stroke patients without history of
      diabetes were included. Fasting and oral glucose tolerance test (OGTT)-derived
      measures of insulin resistance were calculated along with homeostasis model
      assessment of insulin resistance (HOMA-IR) and composite insulin sensitivity
      index (ISI). Insulin resistance was defined by the highest HOMA-IR quartile (Q4)
      and the lowest composite ISI quartile (Q1). RESULTS: Among 1,196 patients, HOMA
      IR Q4 (insulin resistance) vs. Q1-3 was associated with increased 1-year
      mortality (adjusted hazards ratio [HR] 1.83, 95% CI 1.07-3.13) and poor
      functional outcome (adjusted OR 1.97, 95% CI 1.32-2.95) only in participants with
      an eGFR >=90 mL/min/1.73 m2. By comparison, composite ISI Q1 (insulin resistance)
      vs. Q2-4 was associated with higher risks of 1-year mortality (adjusted HR 3.64,
      0.90-14.78; 2.50, 1.19-5.26; and 1.99, 1.17-3.39, respectively) and poor
      functional outcome (adjusted OR 3.62, 1.08-12.19; 1.51, 0.85-2.70; and 2.25, 1.42
      3.57, respectively) in all 3 subgroups with eGFR < 60, 60-89, and >=90
      mL/min/1.73 m2. CONCLUSIONS: An OGTT-derived estimate of insulin resistance with
      the composite ISI, but not HOMA-IR, was independently associated with increased
      risks of 1-year mortality and poor functional outcome in non-diabetic ischemic
      stroke patients with different eGFR strata.

PMID- 30235442
TI  - Genipin Reverses HFD-Induced Liver Damage and Inhibits UCP2-Mediated Pyroptosis
      in Mice.
AB  - BACKGROUND/AIMS: Liver damage is a typical manifestation of nonalcoholic fatty
      liver disease (NAFLD). It originates from excessive fat accumulation, leading to
      hepatocyte death, inflammation, and fibrosis. Nonalcoholic steatohepatitis (NASH)
      is a type of NAFLD with a prevalence of 49% in morbidly obese patients.
      Pyroptosis plays an important role in the development of NASH; thus, it is
      important to elucidate the effect of lipid accumulation on pyroptosis. Genipin
      (GNP), a natural water-soluble cross-linking agent, has hepatoprotective effects
      and decreases lipid accumulation in the liver; however, the mechanisms underlying
      these effects are unknown. METHODS: In this study, qPCR and Western blot were
      used to examine pyroptotic gene expression in high-fat diet (HFD) induced obese
      mice and free fatty acids (FFAs) treated hepatocytes. At the same time, relative
      lactate dehydrogenase (LDH) release and Hoechst & propidium iodide (PI) staining
      were done to verify cell death. To explore the molecular mechanism, cell
      transfection were constructed with siRNA or plasmid to obtain knockdown or
      overexpression hepatocytes. RESULTS: We found that HFD-fed mice and FFAs-treated
      hepatocytes had obvious pyroptosis, and addition of GNP reversed liver damage and
      inhibited pyroptosis both in vitro and in vivo. Besides, UCP2 knockdown cells
      showed suppressed FFAs-mediated pyroptosis, as determined by decreased pyroptotic
      gene expression, reduced lactate dehydrogenase (LDH) release, and reduced cell
      death. Consistent with this, cells transfected with UCP2 had upregulated
      pyroptotic gene expression, increased LDH release, and increased cell death.
      CONCLUSION: GNP reverses HFD-induced liver damage and inhibits UCP2-mediated
      pyroptosis. Thus, GNP may serve as a potential therapeutic candidate for NAFLD.

PMID- 30235444
TI  - The Status of Epstein-Barr Virus Infection in Intestinal Mucosa of Chinese
      Patients with Inflammatory Bowel Disease.
AB  - AIMS: This cross-sectional study is to investigate the presence of Epstein-Barr
      virus (EBV) in colonic mucosa of inflammatory bowel disease (IBD) patients and
      its correlation with the clinical disease activities and therapeutic regimens.
      METHODS: Subjects undergoing colonoscopy for screening of polyps were recruited
      as control. EBV DNA load was analyzed by means of quantitative real-time
      polymerase chain reaction and EBV-encoded RNAs were tested by in situ
      hybridization in intestinal mucosa of IBD patients. EBV infection was defined as
      positive with either method. Clinical disease activity was assessed using the
      Mayo Clinic Score for ulcerative colitis and Crohn's disease activity index for
      CD. RESULTS: EBV was detectable in 33 out of 99 IBD patients (33.3%). In
      controls, EBV prevalence was 7.5% (3/40). We found a significant correlation
      between EBV prevalence and clinical disease activities (mild [10.71%, 3/28]
      versus moderate [32.73%, 18/55], severe [75.00%, n = 12/16], p < 0.001). However,
      no significant difference was found in EBV prevalence between patients who
      received immunosuppressive therapy and those who did not. CONCLUSIONS: EBV
      infection is common in colonic mucosa of IBD patients. There is a significant
      correlation between EBV infection and clinical disease activities of IBD.
      However, prospective studies are still needed to explore the exact role of EBV in
      IBD.

PMID- 30235443
TI  - Inhibition of Histone Deacetylases Prevents Cardiac Remodeling After Myocardial
      Infarction by Restoring Autophagosome Processing in Cardiac Fibroblasts.
AB  - BACKGROUND/AIMS: Histone deacetylases (HDACs) play a critical role in the
      regulation of gene transcription, cardiac development, and diseases. The aim of
      this study was to investigate whether the inhibition of HDACs improves cardiac
      remodeling and its underlying mechanisms in a mouse myocardial infarction (MI)
      model. METHODS: The HDAC inhibitor trichostatin A (TSA, 0.1 mg/kg/day) was
      administered via daily intraperitoneal injections for 8 consecutive weeks after
      MI in C57/BL mice. Echocardiography and tissue histopathology were used to assess
      cardiac function. Cultured neonatal rat cardiac fibroblasts (NRCFs) were
      subjected to simulated hypoxia in vitro. Autophagic flux was measured using the
      tandem fluorescent mCherry-GFP-LC3 assay. Western blot was used to detect
      autophagic biomarkers. RESULTS: After 8 weeks, the inhibition of HDACs in vivo
      resulted in improved cardiac remodeling and hence better ventricular function. MI
      was associated with increased LC3-II expression and the accumulation of autophagy
      adaptor protein p62, indicating impaired autophagic flux, which was reversed by
      TSA treatment. Cultured NRCFs exhibited increased cell death after simulated
      hypoxia in vitro. Increased cell death was associated with markedly increased
      numbers of autophagosomes but not autolysosomes, as assessed by punctate dual
      fluorescent mCherry-green fluorescent protein tandem-tagged light chain-3
      expression, indicating that hypoxia resulted in impaired autophagic flux.
      Importantly, TSA treatment reversed hypoxia-induced impaired autophagic flux and
      led to a 40% decrease in cell death. This was accompanied by improved
      mitochondrial membrane potential. The beneficial effects of TSA therapy were
      abolished by RNAi intervention targeting LAMP2; likewise, in vivo delivery of
      chloroquine abolished the TSA-mediated cardioprotective effects. CONCLUSION: Our
      results provide evidence that the HDAC inhibitor TSA prevents cardiac remodeling
      after MI and is dependent on restoring autophagosome processing of cardiac
      fibroblasts.

PMID- 30235445
TI  - Z-Score Reference Ranges for the Offset of the Tricuspid Septal Leaflet in Normal
      Fetuses.
AB  - OBJECTIVES: To determine Z-score equations and reference ranges for mitral valve
      tricuspid valve distance (MTD) and the MTD index in the fetal heart. METHODS: A
      prospective cross-sectional study was performed in 899 normal singleton fetuses
      from 14 to 40 weeks' gestation. The MTD and interventricular septum length (IVSL)
      were measured offline after electronic cardiac spatiotemporal image correlation
      volume acquisition. The MTD index was determined as the ratio of MTD to IVSL. Z
      score reference ranges of these measurements were determined against gestational
      age (GA) and estimated fetal weight (EFW), using regression analysis of the mean
      and standard deviation (SD). RESULTS: Strong positive correlations were found
      between the MTD and the independent variables. A simple linear regression model
      was the best description of the mean and SD of MTD based on GA, while a cubic
      regression best fitted the mean MTD against EFW. In contrast, the MTD index
      decreased progressively with the independent variables. Fractional polynomials
      best fitted the MTD index in terms of GA and EFW. CONCLUSION: Normal reference
      values and Z-scores of fetal MTD and MTD index were provided against GA and EFW,
      which may be useful tools for quantitative assessment of some cardiac and
      extracardiac diseases.

PMID- 30235446
TI  - Use of the Endometriosis Fertility Index to Predict Natural Pregnancy after
      Endometriosis Surgery: A Single-Center Study.
AB  - AIMS: Our objective was to predict natural pregnancy after endometriosis surgery
      using the endometriosis fertility index (EFI). METHODS: A retrospective medical
      records review was conducted, examining patients surgically treated for
      endometriosis at a single center in Korea between January 2009 and February 2015.
      In total, 68 women attempting natural conception were analyzed by assessing age,
      preoperative serum CA-125, body mass index, revised American Fertility Society
      (rAFS) stage, EFI, and pregnancy outcome. Kaplan-Meier estimates and log-rank
      tests were used to generate cumulative natural pregnancy rate curves based on an
      EFI cut-point. A receiver-operating characteristic (ROC) curve was plotted for
      EFI. RESULTS: Seventy-seven patients attempted conceptions, resulting in 33
      natural and 9 assisted conceptions. Excluding assisted conceptions, the mean EFI
      scores of 68 women who were not pregnant and pregnant were 5.43 +/- 0.36 and 6.88
      +/- 0.28 respectively. The relation between EFI and natural pregnancy was
      significant (cumulative overall pregnancy rate, p = 0.006), whereas rAFS stage
      was not (univariate logistics, p = 0.853). The cut-point for maximum natural
      pregnancy outcomes was 6 (area under ROC curve = 0.710, 95% CI 0.586-0.835).
      CONCLUSION: The EFI is a reliable staging system for predicting natural pregnancy
      after endometriosis surgery. EFI scores can be used to guide postoperative
      treatment of women with endometriosis.

PMID- 30235448
TI  - Deletion and Functional Analysis of Hepatitis B Virus X Protein: Evidence for an
      Effect on Cell Cycle Regulators.
AB  - BACKGROUND/AIMS: The hepatitis B virus X protein (HBx) is a viral trans-activator
      that plays a crucial role in pathogenesis of hepatocellular carcinoma (HCC) via
      an unknown mechanism. The role of HBx in modulating cell proliferation and
      programmed cell death is replete with controversies. Thus, the goal of this study
      was to elucidate the effect of HBx and its deletion mutants on cell cycle
      progression in human hepatoma cells. METHODS: Huh7 cells transfected with either
      full-length or truncated HBx were tested for their mitogenic potential based on
      their effect on the expression of key cell cycle-related proteins (p27, cyclin
      D1, p21, and p53) and pro-apoptotic proteins such as cleaved poly (ADP-ribose)
      polymerase (PARP) and Bax. Western blotting and immunofluorescence techniques
      were applied to detect changes in the expression levels and intracellular
      localization, respectively, of the investigated proteins. Also, Quantitative real
      time PCR (qRT-PCR) was used to detect changes in RNA levels. RESULTS: An
      increased anchorage-independent growth of cells transfected with HBx-WT and its
      deletion mutants was observed. The cell cycle regulatory molecules were
      differentially modulated by full-length HBx (1-154) and its different N- and C
      terminal truncated forms (HBx (31-154), HBx (61-154), HBx (1-94), and HBx (61
      124)). An enhanced modulation of p27, p21, and cyclin D1 was associated with HBx
      (1-154), whereas p53 expression was significantly inhibited by HBx (61-124).
      Similarly, the expression of cleaved PARP and Bax was efficiently suppressed by
      HBx (1-94) and HBx (61-154). CONCLUSION: The HBx-WT and its mutants play a
      critical role in the pathogenesis and progression of HCC by modulating cell cycle
      regulatory proteins.

PMID- 30235447
TI  - Pterostilbene Reduces Acetaminophen-Induced Liver Injury by Activating the Nrf2
      Antioxidative Defense System via the AMPK/Akt/GSK3beta Pathway.
AB  - BACKGROUND/AIMS: Pterostilbene (Pts), a natural dimethylated analog of
      resveratrol from blueberries, exerts antioxidative and anti-apoptotic effects in
      various diseases. This study aims to investigate the protective effects and
      mechanism of Pts against acetaminophen (APAP)-induced hepatotoxicity in vivo.
      METHODS: C57BL/6 mice were treated with APAP or APAP+Pts. HepG2 cells were used
      to further explore the underlying mechanisms in vitro. The effects of Pts on
      hepatotoxicity were measured by commercial kits, Hematoxylin and Eosin (H&E)
      straining, TUNEL assay, Western blot analysis, and Flow cytometry assay. RESULTS:
      In vivo, Pts treatment effectively protected against APAP-induced severe liver
      injury by decreasing the lethality rate, the serum alanine transaminase (ALT) and
      aspartate aminotransferase (AST) levels, liver histological injury, liver
      malondialdehyde (MDA) formation and myeloperoxidase (MPO) levels and by
      increasing liver glutathione (GSH) and superoxide dismutase (SOD) levels.
      Moreover, in Pts-treated mice, the nuclear factor-erythroid 2-related factor 2
      (Nrf2)/heme oxygenase-1 (HO-1) pathway was activated; however, APAP-induced c-Jun
      NH2-terminal kinase (JNK) activation, mitochondrial Bcl-2 Associated X Protein
      (Bax) translocation, apoptosis-inducing factor (AIF) levels and cytochrome c
      release were attenuated. In vitro, Pts was found to reverse hydrogen peroxide
      (H2O2) -induced cytotoxicity, reactive oxygen species (ROS) production and
      apoptosis that depended on Nrf2 activation. Moreover, Pts induced a dose
      dependent increase in the phosphorylation of AMP-activated protein kinase (AMPK),
      serine/threonine kinase (Akt), and glycogen synthase kinase 3beta (GSK3beta) in
      HepG2 cells. Moreover, Pts protect against APAP or H2O2-induced toxicity were
      effectively attenuated or abolished in HepG2 Nrf2-/- cells and Nrf2-/- mice.
      CONCLUSION: Our data suggest that Pts protects against APAP-induced toxicity by
      activating Nrf2 via the AMPK/Akt/GSK3beta pathway.

PMID- 30235449
TI  - Clinical Characteristics and Prognostic Factors of Primary Splenic Angiosarcoma:
      A Retrospective Clinical Analysis from China.
AB  - BACKGROUND/AIMS: Primary splenic angiosarcoma is an aggressive malignancy
      originating from endothelial cells with a particularly poor outcome despite
      radical therapy. Owing to its extremely low incidence, available data for splenic
      angiosarcoma are limited. The present study aimed to address this limitation by
      presenting a thorough retrospective analysis of Chinese primary splenic
      angiosarcoma patients over a 53-year period (1963-2016). METHODS: To determine
      the characteristics of Chinese primary splenic angiosarcoma and identify factors
      that impact the outcomes of this histology, we retrospectively retrieved reports
      of 110 Chinese primary splenic angiosarcoma cases published between 1963-2012.
      RESULTS: In total, 61 males and 49 females diagnosed with primary splenic
      angiosarcoma were included in the present study. The median age at diagnosis was
      50 years (range 2.5-76 years). Of these patients, 25.5% had received prior
      radiotherapy. The rate of splenic rupture was 59.11%. The 1-year overall survival
      rate was 19.1% with a median overall survival time of 8.1 months. Age, gender,
      and radiation history showed no correlation with survival rate. However, by
      univariate analysis, we found that significant adverse predictors of survival
      were splenic rupture before surgery and large tumor size (> 5 cm), while adjuvant
      chemotherapy was a favorable predictor. Furthermore, multivariate analysis
      revealed that splenic rupture and adjuvant chemotherapy were independent adverse
      and favorable predictors, respectively. CONCLUSION: Our large series describes
      and confirms the characteristics and poor prognosis of Chinese primary splenic
      angiosarcoma, thus indicating a critical role for early diagnosis and surgical
      intervention (prior to rupture) in management, and highlights the promising
      potential of adjuvant chemotherapy for improving the outcome in these cases.

PMID- 30235450
TI  - Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis Through miR
      3546/SOX4/Survivin Axis in Rat Thy-1 Nephritis.
AB  - BACKGROUND/AIMS: The activation of complement system and the formation of C5b-9
      complex have been confirmed in the glomeruli of patients with
      mesangioproliferative glomerulonephritis (MsPGN). However, the role and mechanism
      of C5b-9-induced injury in glomerular mesangial cell (GMC) are poorly understood.
      Rat Thy-1N is an animal model for studying MsPGN. It has been revealed that the
      attack of C5b-9 to the GMC in rat Thy-1N is sublytic, and sublytic C5b-9 can
      cause GMC apoptosis, but the underlying mechanism is not fully elucidated. To
      explore the role and regulatory mechanism of C5b-9 in MsPGN lesion, we used rat
      Thy-1N model and first detected the change of microRNA (miRNA) profiles both in
      Thy-1N rat renal tissues (in vivo) and in the cultured GMCs with sublytic C5b-9
      stimulation (in vitro). Then we determined the effect of miR-3546, which
      increased both in vivo and in vitro, on GMC apoptosis upon sublytic C5b-9 as well
      as the involved mechanism. METHODS: Rat Thy-1N model was established and GMCs
      were treated with sublytic C5b-9. The rat renal cortex and the stimulated GMCs
      were obtained for miRNA microarray detection. Subsequently, the increased miRNAs
      were verified by real-time PCR. Meanwhile, to ascertain the ability of some
      miRNAs to upregulate cleaved caspase 3 and induce GMC apoptosis, the
      corresponding miRNA mimics were transfected into GMCs, followed by western
      blotting (WB) and flow cytometry mesurement. Thereafter, the miR-3546-targeted
      gene (SOX4) was predicted using bioinformatics approaches, and SOX4 expression in
      Thy-1N tissues and in the GMCs upon sublytic C5b-9 stimulation or miR-3546
      mimic/inhibitor transfection were detected using real-time PCR and WB. To prove
      that miR-3546 can affect SOX4 gene transcription and SOX4 can regulate survivin
      expression, dual luciferase reporter assay, real-time PCR, WB and chromatin
      immunoprecipitation (ChIP) assays were performed. Furthermore, the role of miR
      3546/SOX4/survivin axis in the GMC apoptosis induced by sublytic C5b-9 was
      examined using WB and flow cytometry. RESULTS: Compared with normal renal tissues
      and untreated GMCs, there were 43 and 62 upregulated miRNAs (> 2-fold) in Thy-1N
      tissues and sublytic C5b-9-stimulated GMCs respectively. A total of 17 miRNAs
      were increased both in vivo and in vitro, 11 of which were validated by real-time
      PCR. Among them, miR-3546 could markedly promote GMC apoptosis and inhibit SOX4
      or survivin expression in response to sublytic C5b-9, and either SOX4 or survivin
      overexpression markedly rescued the GMC apoptosis mediated by miR-3546 mimic.
      Additionally, SOX4 overexpression could reverse the survivin suppression by miR
      3546 mimic, and SOX4 could bind to survivin promoter (-1,278 to -853 nt) and
      activate survivin gene transcription. CONCLUSION: MiR-3546/ SOX4/survivin axis
      has a promoting role in the GMC apoptosis triggered by sublytic C5b-9, and our
      findings may provide a new insight into the pathogenesis of rat Thy-1N and human
      MsPGN.

PMID- 30235451
TI  - Apelin-13 Administration Protects Against LPS-Induced Acute Lung Injury by
      Inhibiting NF-kappaB Pathway and NLRP3 Inflammasome Activation.
AB  - BACKGROUND/AIMS: Acute lung injury (ALI) is induced by a variety of external and
      internal factors and leads to acute progressive respiratory failure. Previous
      studies have shown that apelin-13 can decrease the acute lung injury induced by
      LPS, but the specific mechanism is unclear. Therefore, a mouse lung injury model
      and a cell model were designed to explore the mechanism of how apelin-13
      alleviates the acute lung injury caused by LPS. METHODS: The effect of apelin-13
      on LPS-induced structural damage was determined by H&E staining and by the
      wet/dry weight ratio. The related inflammatory factors in BALF were examined by
      ELISA. The apoptotic pathway and the NF-kappaB and NLRP3 inflammasome pathways
      were evaluated by using Western blotting and immunofluorescence staining.
      RESULTS: LPS induced the structural damage and the production of inflammatory
      cytokines in the lung tissues of mice. These deleterious effects were attenuated
      by apelin-13 administration. The protective effects of apelin-13 were associated
      with decreased reactive oxygen species (ROS) formation and the inhibition of the
      activation of the NF-kappaB and NLRP3 inflammasome pathways in mice and in
      Raw264.7 cells. CONCLUSION: Taken together, these data suggest that apelin-13
      administration ameliorates LPS-induced acute lung injury by suppressing ROS
      formation, as well as by inhibiting the NF-kappaB pathway and the activation of
      the NLRP3 inflammasome in the lungs.

PMID- 30235454
TI  - Unmet Needs in Appendiceal Neuroendocrine Neoplasms.
AB  - Appendiceal neuroendocrine neoplasms (ANEN) are mostly discovered coincidentally
      during appendicectomy and usually have a benign clinical course, thus
      appendicectomy alone is considered as curative. However in some cases a malignant
      potential is suspected and therefore additional operations, such as completion
      right hemicolectomy, are considered. The existing European Neuroendocrine Tumour
      Society (ENETS) guidelines provide quite useful data about epidemiology and
      prognosis, as well as, practical recommendations with regards to the risk factors
      for a more aggressive disease course and the indications for a secondary
      operation. However, those guidelines are based on heterogeneous and retrospective
      studies. Therefore, the evidence does not seem to be robust and there are still
      unmet needs in terms of accurate epidemiology and overall prognosis, optimal
      diagnostic and follow-up strategy, and identified risk factors, which would
      indicate a more aggressive surgical approach at the beginning and a more intense
      follow-up. In this review, we are attempting a critical approach of ENETS
      guidelines and published series for ANEN, focusing on the above noted "grey
      areas".

PMID- 30235452
TI  - Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK
      and Fatty Acid beta-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese
      Mice.
AB  - BACKGROUND/AIMS: Fisetin is a naturally abundant flavonoid isolated from various
      fruits and vegetables that was recently identified to have potential biological
      functions in improving allergic airway inflammation, as well as anti-oxidative
      and anti-tumor properties. Fisetin has also been demonstrated to have anti
      obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty
      liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether
      fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and
      regulates lipid metabolism of FL83B hepatocytes in vitro. METHODS: NAFLD was
      induced by HFD in male C57BL/6 mice. The mice were then injected
      intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells
      were challenged with oleic acid to induce lipid accumulation and treated with
      various concentrations of fisetin. RESULTS: NAFLD mice treated with fisetin had
      decreased body weight and epididymal adipose tissue weight compared to NAFLD
      mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte
      steatosis, alleviated serum free fatty acid, and leptin concentrations,
      significantly decreased fatty acid synthase, and significantly increased
      phosphorylation of AMPKalpha and the production of sirt-1 and carnitine
      palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid
      accumulation and increased lipolysis and beta-oxidation in hepatocytes.
      CONCLUSION: This study suggests that fisetin is a potential novel treatment for
      alleviating hepatic lipid metabolism and improving NAFLD in mice via activation
      of the sirt1/AMPK and beta-oxidation pathway.

PMID- 30235455
TI  - Kidney Response to Heart Failure: Proteomic Analysis of Cardiorenal Syndrome.
AB  - BACKGROUND/AIMS: Chronic heart failure (HF) disrupts normal kidney function and
      leads to cardiorenal syndrome that further promotes HF progression. To identify
      potential participants in HF-related injury, we analyzed kidney proteome in an
      established HF model. METHODS: HF was induced by chronic volume overload in male
      HanSD rats using aorto-caval fistula. After 21 weeks, cardiac and renal functions
      (in-situ kidney study) and renal proteomics were studied in sham-operated
      (controls) and HF rats, using iTRAQ labeling and LC-MS with Orbitrap Fusion,
      leading to identification and quantification of almost 4000 proteins. RESULTS:
      Compared to controls, HF rats had cardiac hypertrophy, systemic and pulmonary
      congestion. Kidneys of HF rats had reduced renal blood flow, sodium excretion and
      urine production. While glomerular filtration rate, serum cystatin C and
      creatinine were still normal compared to controls, HF kidneys showed albuminuria
      and markedly increased tissue angiotensin-II levels (5-fold). HF kidneys (versus
      controls) displayed differential expression (?1.5-fold) of 67 proteins. The most
      upregulated were angiotensin-converting enzyme (ACE, ?20-fold), advanced
      glycosylation product-specific receptor (RAGE, 14-fold), periostin (6.8-fold),
      caveolin-1 (4.5-fold) and other proteins implicated in endothelial function (vWF,
      cavins 1-3, T-kininogen 2), proinflammatory ECM activation (MFAP4, collagen-VI,
      galectin-3, FHL-1, calponin) and proteins involved in glomerular filtration
      membrane integrity (CLIC5, ZO-1). Carboxylesterase-1D (CES1D), an enzyme that
      converts ACE inhibitors or sacubitril into active drugs, was also upregulated in
      HF kidneys. CONCLUSION: Chronic HF leads to latent kidney injury, associated with
      deep changes in kidney protein composition. These alterations may act in concert
      with intrarenal renin-angiotensin system activation and may serve as markers
      and/or targets to tackle cardiorenal syndrome.

PMID- 30235453
TI  - miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled
      Related Protein-1 in Cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Cholangiocarcinoma (CCA) is one of the most common malignant
      tumors of the biliary tract originating from biliary epithelial cells. Although
      many therapeutic strategies have been developed to treat CCA, the survival rate
      for CCA patients is still quite low. Thus it is urgent to elucidate the
      pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been
      shown to be associated with many human solid cancers, but the function of miR-191
      in CCA is still poorly understood. METHODS: We first investigated the expression
      level of miR-191 in human CCA tissues and cell lines with quantitative real-time
      PCR (qRT-PCR). The effects of miR-191 on CCA cells were determined by Cell
      Counting Kit-8 assay, colony formation assay and acridine orange/ethidium bromide
      staining. Finally, we utilized qRT-PCR, western blot and luciferase reporter
      assays to verify the miR-191 target gene. RESULTS: We showed that miR-191 was up
      regulated in CCA cell lines and patients. Knockdown of miR-191 by transfection of
      its inhibitor sequence blocked RBE cells viability and induced apoptosis of RBE
      cells. Both qRT-PCR and western blot analysis showed that the secreted frizzled
      related protein-1 (sFRP1) level was negatively correlated with that of miR-191.
      Luciferase assay validated that sFRP1 was a direct target of miR-191. Moreover,
      knockdown of miR-191 led to suppression of Wnt/beta-catenin signaling activation.
      Co-transfection of sFRP1 small interfering RNA (siRNA) and miR-191 inhibitor re
      activated the Wnt/beta-catenin signaling pathway as detected by an increased
      level of beta-catenin and phosphorylation of GSK-3beta, and restored the
      expression of survivin and c-myc in RBE cells. Co-transfection of sFRP1 siRNA
      with miR-191 inhibitor restored the colony formation ability and viability of RBE
      cells. CONCLUSION: Taken together, our results demonstrate a novel insight into
      miR-191 biological function in CCA. Our findings suggest that miR-191 is a
      potential therapeutic target of CCA treatment.

PMID- 30235456
TI  - Incidence of Hypersensitivity Reactions During Hemodialysis.
AB  - BACKGROUND/AIMS: A recent alert from Spanish health authorities warned of a
      higher incidence of reported hypersensitivity reactions to hemodialysis membranes
      with polysulfone, in the 2017 review of acute reactions to dialyzers found only
      published reports in the 21st century on polysulfone and its derivatives. The aim
      is to assess/evaluate the current incidence and characteristics of
      hypersensitivity reactions in hemodialysis patients. METHODS: A retrospective
      multicentre study in 9 Spanish hospitals evaluated patients in whom a
      hypersensitivity reaction required a change in dialyzer membrane. RESULTS: A
      total of 37 patients out of 1561 (2.37%) had hypersensitivity reactions and
      clinical, epidemiological and analytical data were available for 33 patients
      (2.11%). The membranes involved were polysulfone (n=23), polynephron (n=8),
      polyethersulfone (n=1) and polyacrylonitrile (n=1). This distribution reflected
      the frequency of use of membranes in the participating dialysis units. The
      reactions were described as type A in 18 cases and type B in 15 cases. There were
      no significant differences between the two types in clinical symptoms, the
      composition of the membrane involved, the method of sterilization, the season, or
      the time during the session in which they occurred. The most frequent symptom was
      dyspnea/breathlessness (64% of reactions). Eosinophilia was common (74%). 54% of
      the reactions occurred within the first 30 minutes of hemodialysis, 64% occurred
      during the first year of dialysis, and 54% required discontinuation of dialysis
      session. Cellulose triacetate was used as an alternative dialyzer in 78% of the
      cases. CONCLUSION: The incidence of hypersensitivity reactions was in the range
      found in reports from 20 years ago and is observed associated with synthetic
      membranes, not just polysulfones. Cellulose triacetate appears to be a good
      alternative for these patients.

PMID- 30235457
TI  - Association of Serum Uric Acid with Arterial Stiffness in Peritoneal Dialysis
      Patients.
AB  - BACKGROUND/AIMS: Serum uric acid (SUA) has been proposed as a mediator associated
      with increased cardiovascular risk and arterial stiffness. However, evidence on
      the association between SUA and arterial stiffness in peritoneal dialysis (PD)
      patients is lacking. The aim of this study was to examine the relationship
      between SUA and arterial stiffness in PD patients. METHODS: The patients who
      performed vascular profiler test from January 1, 2014 to October 31, 2016, and
      with SUA values were enrolled. Arterial stiffness was evaluated by brachial-ankle
      pulse wave velocity (baPWV). The relationship between SUA and baPWV was tested by
      multiple linear regression models. RESULTS: Of 645 PD patients, mean SUA was 6.80
      (+/-1.29) mg/dL, mean baPWV was 1713 (+/-505) cm/s. In fully adjusted linear
      regression models, higher SUA was significantly associated with higher baPWV in
      young [standardized coefficients (beta), 0.085; 95% confidence interval (95% CI),
      0.013 to 0.130; P=0.02] but not in elderly (beta, -0.194; 95% CI, -0.774 to
      0.093; P=0.1) PD patients. In gender-stratified models of young patients, there
      was a significant association between SUA and baPWV in male (beta, 0.115; 95% CI,
      0.015 to 0.182; P=0.02) but not in female. Male in the highest gender-specific
      SUA quartile had a higher baPWV than those in the lowest quartile (beta, 0.132;
      95% CI, 0.011 to 0.209; P=0.03). This gender difference was reversed when
      selecting male patients with lower SUA levels (quartile 1 and 2) and female
      patients with higher SUA levels (quartile 3 and 4). CONCLUSION: SUA was
      positively associated with baPWV in young PD patients, and this association was
      significant in males but not in females, which is possibly explained by the
      higher SUA level in males than in females.

PMID- 30235458
TI  - Immune Thrombocytopenia - Current Diagnostics and Therapy: Recommendations of a
      Joint Working Group of DGHO, OGHO, SGH, GPOH, and DGTI.

PMID- 30235459
TI  - Antioxidant Properties of Ferulic Acid and Its Possible Application.
AB  - Ferulic acid has low toxicity and possesses many physiological functions (anti
      inflammatory, antioxidant, antimicrobial activity, anticancer, and antidiabetic
      effect). It has been widely used in the pharmaceutical, food, and cosmetics
      industry. Ferulic acid is a free radical scavenger, but also an inhibitor of
      enzymes that catalyze free radical generation and an enhancer of scavenger enzyme
      activity. Ferulic acid has a protective role for the main skin structures:
      keratinocytes, fibroblasts, collagen, elastin. It inhibits melanogenesis,
      enhances angiogenesis, and accelerates wound healing. It is widely applied in
      skin care formulations as a photoprotective agent, delayer of skin photoaging
      processes, and brightening component. Nonetheless, its use is limited by its
      tendency to be rapidly oxidized.

PMID- 30235460
TI  - Holmium Laser Enucleation of the Prostate Provides Similar Incidental Prostate
      Cancer Detection Rates as Open Prostatectomy: A Matched Pair Analysis.
AB  - INTRODUCTION: Whereas the excellent functional outcomes after Holmium laser
      enucleation of the prostate (HoLEP) and its equivalency to open prostatectomy
      (OP) have been studied in detail in the past years, the oncological equivalency
      has yet to be investigated. Therefore, we conducted a matched pair analysis to
      evaluate and compare incidental prostate cancer detection rates after HoLEP and
      OP. PATIENTS AND METHODS: Preoperative patient age, total prostate-specific
      antigen (PSA), and prostate volume were used as primary matching criteria.
      Descriptive statistics were used to confirm matching quality. Statistical
      analyses were performed using Fisher's exact test and T-test or Mann-Whitney U
      test for dichotomous and continuous variables, respectively. RESULTS: After the
      matching procedure, 72 out of 145 patients after HoLEP and 72 out of 477 patients
      after OP were included. Mean patient age (70 vs. 71 years), median prostate
      volume (106 vs. 107 mL), and median preoperative total PSA (4.32 vs. 4.36 ng/mL)
      were almost identical. The amount of removed tissue did not differ between HoLEP
      and OP. Incidental prostate cancer detection rate was similar with 9.7% after
      HoLEP and 8.3% after OP (p = 1.000). CONCLUSION: This first matched pair analysis
      shows that HoLEP does not have a disadvantage regarding cancer detection rate
      during desobstructive surgery for large prostates.

PMID- 30235461
TI  - Alexithymia, Ego-Dystonicity, and Obsessive-Compulsive Symptoms: A Path Modeling
      Analysis.
AB  - AIMS: This cross-sectional study aimed to test the path relations between
      alexithymia, ego-dystonicity, anxiety, depression and obsessive-compulsive (OC)
      symptoms in obsessive-compulsive disorder (OCD) and healthy individuals. METHODS:
      Fifty-eight patients with OCD (mean age 35.5 years) and 54 healthy participants
      (mean age 33.5 years) completed an assessment via a structured clinical
      interview. All of them completed the Toronto Alexithymia Scale (TAS-20), the
      Vancouver Obsessive-Compulsive Inventory (VOCI), the Self-Consistency and
      Congruence Scale (SCCS), the Self-Rating Anxiety Scale (SAS) and the Self-Rating
      Depression Scale (SDS). The data were analyzed using partial least squares
      structural equation modeling (PLS-SEM). RESULTS: In the OCD patients, alexithymia
      (a linear combination of difficulty identifying and describing emotions in the
      self) was associated with the OC symptoms either with or without the presence of
      ego-dystonicity (a profile of self-inconsistency and self-stereotype). In the
      heathy participants, alexithymia was associated with the OC symptoms only through
      ego-dystonic experiences. CONCLUSION: This study provides evidence that ego
      dystonicity partially affects the association between alexithymia and obsessive
      compulsions. Alexithymia and ego-dystonicity have a synergistic effect on the
      symptoms of OCD. Alexithymia in healthy participants associates to the OC
      symptoms only through ego-dystonicity. Targeting ego-dystonicity dimensions in
      psychotherapy would help improve the symptoms of OCD.

PMID- 30235462
TI  - Evaluating Guideline Adherence for T1 Bladder Cancer Treatment and Surveillance:
      A Retrospective German Multicenter Observation.
AB  - INTRODUCTION: To mirror guideline-adherence for pT1 bladder cancer treatment in
      Northern Germany. MATERIALS AND METHODS: Overall, 111 patients with pT1 diagnosis
      were treated at 4 institutions. Guideline-adherence was defined as repeat
      resection, instillation, and quarterly cystoscopy. Patient characteristics and
      pathological parameters were assessed. We summarized patients using descriptive
      analyses and evaluated guideline-adherence within selected subgroups. We created
      a multivariable model to identify predictors of guideline-adherence. RESULTS:
      Median age was 75 years (range 39-94 years), multifocal tumors were found in
      44.1%, early instillation was performed in 33.3%, and repeat resection was
      performed in 77.5%. Of 62.2% who underwent instillation, 59.4% received BCG,
      while 40.6% received Mitomycin C or other agents. Cystoscopic follow-up was
      performed in 81.8%. Guideline-adherence was met in 56.8%. Patients aged below the
      median met adherence metrics more often compared to those above the median (66.7
      vs. 46.3%; p = 0.030). Men more frequently met adherence metrics compared to
      women (62.1 vs. 37.5%; p = 0.038). More patients with multifocal tumors met all 3
      adherence metrics (69.4 vs. 48.0%; p = 0.050), as compared to those with unifocal
      lesions. In multivariable analyses, age-adjusted comorbidity (OR 0.75; 95% CI
      0.59-0.94; p = 0.011) and multifocality (OR 2.62; 95% CI 1.09-6.27; p = 0.031)
      were predictors of guideline-adherence. CONCLUSIONS: We found non-adherence in
      more than one-third of patients and disparities among patients of different age
      and according to tumor focality. Larger samples and prospective studies are
      needed to delineate and eradicate treatment disadvantages in these high-risk
      patients.

PMID- 30235463
TI  - Title Page / Editorial Board / Disclosure Statement / Imprint / Inhalt.

PMID- 30235464
TI  - ?

PMID- 30235465
TI  - [Impact of merging healthcare organizations: a review of the literature].
AB  - Over the last two decades, the healthcare sector of different Countries has been
      involved in a wave of mergers. This wave first started in the US and in the UK
      and, later, has involved Italy. Despite these activities are still pursued,
      little attention is paid to the assessment of their impact. The aim of this study
      is to summarize, through a review of the literature, evidence on the impact of
      these mergers. The main results are divided into four areas: the impact of
      mergers on clinical outcome, processes and use of resources; the association
      between population size and performance of primary care organizations; the
      analysis of the main drivers; and eventually, staff perception and satisfaction.
      Evidence is conflicting and small number of indicators of clinical outcome,
      processes and use of resources show a significant improvement. The performance of
      the Primary care Organizations does not seem significantly related to the size of
      the population served but to numerous factors, among others the function of the
      organization itself. Drivers that lead the pursuing of merging can be
      distinguished in stated and unstated drivers the first ones originating from
      public consultation document, the second ones from staff interview. Concerns
      about mergers derive from responses of personnel interview, in particular about
      the cultural differences and the distance perceived from top managers. Evidence
      shows that these processes do not necessarily lead to the expected benefits. It
      is important, therefore, to periodically and systematically assess the impact of
      mergers in a continuous quality improvement cycle that makes professionist,
      recipients and policy maker accountable. These latter, in particular are
      responsible for protecting the health of the community.

PMID- 30235466
TI  - The diagnostic delay of oral carcinoma.
AB  - This paper describes the results of a retrospective study that analyzed the
      extent and role of diagnostic delays on the development and prognosis of oral
      cancer. We consulted the digital archives of the Anatomy and Pathology Department
      of the University Hospital of Modena and Reggio Emilia for the period from 2000
      to 2016, to identify all patients with oral cavity lesions according to the
      SNOMED coding system. In total, 645 reports of squamous cell carcinoma of the
      oral cavity were retrieved. Data collected from the reports was supplemented with
      clinical information, with particular reference to the time of onset of the first
      signs and/or symptoms and the time elapsed between biopsy and definitive
      histological diagnosis following surgery. The average delay of patients from
      onset of signs and/or symptoms and seeking medical care was 112 days, or about 4
      months. A longer delay was found for male with respect to female patients (151
      days versus 82 days respectively; p < 0.015). An average delay of 40 days was
      observed between the first biopsy and the postoperative histological diagnosis.
      Results indicate that diagnostic delays occur frequently in oral tumours and can
      due to both the patient's wait-and-see conduct upon appearance of the first signs
      and/or symptoms, and to the organizational and communicative deficiencies among
      the different medical specialties. In light of these results, we make the
      recommendation to organize information campaigns through the Public Health
      Departments and specific screening programs, and to introduce an operational
      protocol for the prevention and early diagnosis of oral cancer, involving general
      medicine practitioners and dentists as the main promoters.

PMID- 30235468
TI  - [Effectiveness of the Situation-Background-Assessment-Recommendation (SBAR)
      methodology in patient handovers between nurses, Italy].
AB  - Exchange of information between healthcare professionals involved in the care of
      patients is essential for providing effective care. Use of the Situation
      BackgroundAssessment-Recommendation (SBAR) methodology is increasingly indicated
      in the health sector to facilitate communication during handovers of patients
      between clinicians or clinical teams. The present review of the literature aims
      to determine the effectiveness of the SBAR methodology in the handover of nursing
      documentation.

PMID- 30235467
TI  - [Integrating cervical cancer screening and HPV vaccination: a pilot experience in
      the Apulia region of Italy].
AB  - The aim of this study was to describe preliminary performance indicators of the
      cervical cancer screening and HPV vaccination integrated strategy, offered to
      women aged 25 years residing in the province of Foggia (Apulia, Italy). During
      the two-year period 2015-16, receiving HPV vaccination, first dose and/or the
      full vaccination series, was significantly associated with compliance to
      screening (p<0,0001) in the first two birth cohorts (1991 and 1992 cohorts)
      targeted by this integrated strategy.

PMID- 30235469
TI  - [Epidemics of Hepatitis A and opportunities for vaccination: a focus on the
      category of men who practice sex with men (MSM)].
AB  - Hepatitis A is an infectious disease caused by a virus (HAV), which is highly
      contagious and widespread all over the world. In industrialized countries,
      Hepatitis A is commonly considered a disease with an important socio-economic
      impact, as the clinical disease affects mostly young adults. After the
      development of a specific anti-HAV vaccine, a reduction in the incidence of
      Hepatitis A was observed, with a subsequent change in the prevalence of HAV. HAV
      spreads mainly in children and risk categories, whose work or activities or
      medical conditions lead to a close contact with the virus. In particular, in Men
      who have sex with Men (MSM) many outbreaks have been reported in the last five
      years. Aim of this paper is an evaluation of the recent literature about HAV
      infection in MSM in order to update the current guidelines on HAV procedures for
      MSM.

PMID- 30235470
TI  - Ultrasound in the Re-Staging of Cervical Metastases after Chemoradiotherapy for
      Head and Neck Cancer.
AB  - High-resolution ultrasonography, including color duplex modes, is a well
      established and proven imaging method that is used in addition to computed
      tomography for re-staging after primary nonsurgical therapy for head and neck
      cancer in many European countries. No evidence-based international re-staging
      guidelines are available. Decisions as to whether to carry out neck dissection
      after primary radiotherapy or chemoradiotherapy are often made in the relevant
      tumor boards and are therefore subject to variance. High-resolution
      ultrasonography clearly detects morphological changes such as intranodal necrotic
      areas and alterations in the hilar vascularization pattern. Another important
      aspect of ultrasonography is that it allows accurate check-ups on dynamic changes
      during the follow-up period. This article reviews the role of ultrasonography in
      the follow-up and re-staging of patients with neck disease after primary
      chemoradiotherapy.

PMID- 30235471
TI  - Veterinary Cuttable Plate in a Plate-Rod Construct for Repair of Diaphyseal
      Femoral Fractures in the Cat.
AB  - OBJECTIVE:  This study evaluated retrospectively the effectiveness of the
      veterinary cuttable plate (VCP) in a plate-rod construct, for the treatment of
      diaphyseal femoral fractures in cats. MATERIALS AND METHODS:  A total of 29 cats
      with diaphyseal femoral fracture underwent stabilization with a VCP-rod
      construct. RESULTS:  Fractures were classified as type A (7/29), type B (11/29)
      and type C (11/29) following the AO classification. Biological osteosynthesis was
      elected in three type B and 10 type C fractures, and open approach in the other
      cases. Pin diameter was 2 mm (n = 16) or 2.5 mm (n = 13); this corresponded to a
      percentage of pin occupation of 39.9 and 53.0% of the intramedullary cavity
      respectively. The 2.0/2.7-mm VCP and 2-mm screws were used in all cases. The
      median length of the VCP was 12 holes, and the median number of screws placed in
      the plate was 6. The median number of cortices engaged per fragment was 6. Ninety
      nine percent of the screws were bicortical. Quadriceps contracture was an
      unacceptable functional outcome in one cat. Follow-up was available in 20 cases.
      Complete bone healing was assessed in 16/20 cases with a functional outcome
      considered as full in 17/20, acceptable in 2/20, and unacceptable in 1/20.
      Telephonic owner outcome assessment was available for five more cats and was
      considered as full in all cases. CLINICAL SIGNIFICANCE:  The VCP-rod construct is
      effective to manage all configurations of diaphyseal femoral fracture in cats.
      The high amount of screw holes per unit length of a VCP allows bicortical screws
      placement without interfering with the intramedullary rod.

PMID- 30235472
TI  - In Vitro Biomechanical Comparison of Four Different Ventral Surgical Procedures
      on the Canine Fourth-Fifth Cervical Vertebral Motion Unit.
AB  - INTRODUCTION:  Biomechanical properties of four different ventral surgical
      procedures at the canine fourth-fifth cervical (C4-C5) vertebral motion unit
      (VMU) were assessed and compared with the intact C4-C5 VMU. MATERIALS AND
      METHODS:  The third-sixth cervical vertebral column from 24 skeletally mature
      Beagle cadavers were randomly allocated to four groups (standard ventral slot,
      slanted slot, inverted cone slot and intervertebral disc fenestration).
      Standardized tests were performed for each specimen in flexion/extension, lateral
      bending and axial rotation. The specimens were tested intact and after completion
      of one of the three slots techniques or fenestration. Pre-testing, cadaver
      specimens were confirmed to be free of disease by computed tomography (CT)
      examination. Post-testing, dimensions of slots and fenestration were determined
      based on a second CT examination. RESULTS:  All ventral surgical procedures
      increased range of motion (ROM) at the C4-C5 VMU compared with intact specimens.
      The only significant difference in the increase in ROM was observed between
      slanted slot and fenestration in flexion/extension. The standard ventral slot had
      a significant higher increase in ROM in extension compared with the other three
      techniques. The slanted slot had a significant lower increase in ROM in flexion.
      DISCUSSION/CONCLUSION:  The described ventral slot techniques have similar
      biomechanical effects on the canine cervical vertebral column. In contrast to the
      findings of a previous study, the slanted slot and inverted cone slot do not
      appear to provide a biomechanical benefit compared with standard ventral slot.

PMID- 30235473
TI  - Pro-Fibrogenic and Anti-Inflammatory Potential of a Polyphenol-Enriched Fraction
      from Annona crassiflora in Skin Repair.
AB  - A polyphenol-enriched fraction from Annona crassiflora fruit peel (PEF-Ac)
      containing chlorogenic acid, epi-catechin, procyanidins B2 and C1, quercetin
      glucoside, kaempferol, and caffeoyl-glucoside was investigated for its anti
      inflammatory, pro-angiogenic, and profibrogenic potential in the healing of
      cutaneous wounds. Four wounds were performed on the back of C57 mice and the
      lesions were treated with the vehicle (Vaseline and lanolin) and PEF-Ac at
      concentrations of 2%, 4%, and 6% for 4 and 7 d. Neutrophils and macrophages
      activities were evaluated indirectly by the activity of myeloperoxidase and N
      acetyl-beta-D-glycosaminidase, angiogenesis was evaluated by hemoglobin dosing
      and vessel count in histological sections, and collagen deposition was assessed
      from histological sections stained with picrosirius red. PEF-Ac demonstrated anti
      inflammatory activity, with reduced activities of neutrophil and macrophage in
      the cutaneous wounds. In addition, there was an increase in the synthesis of
      types I and III collagen, as well as in the percentage of wound closure, mainly
      after 4 d of treatment. On the other hand, PEF-Ac did not present an effective
      pro-angiogenic activity. A. crassiflora fruit peel showed anti-inflammatory and
      profibrogenic properties, indicating a promising natural source of bioactive
      molecules for treatment of cutaneous wounds.

PMID- 30235474
TI  - Analysis of the Performance of 11 Formulae for Fetal Weight Estimation in Preterm
      Fetuses with Abnormal Doppler Velocimetry - A Retrospective Multicenter Study.
AB  - OBJECTIVE:  To assess 11 formulae commonly used to estimate fetal weight in a
      population of premature fetuses who had abnormal Doppler velocimetry due to early
      onset placental insufficiency. The performance of each formula was evaluated in
      subgroups of fetuses with expected growth and intrauterine growth restriction.
      METHODS:  Data were collected from fetuses and mothers who delivered at three
      Brazilian hospitals between November 2002 and December 2013. We used the
      following formulae: Campbell; Hadlock I, II, III, IV and V; Shepard; Warsof;
      Weiner I and II; and Woo III. RESULTS:  We analyzed 194 fetuses. Of these, 116
      (59.8%) were considered appropriate for gestational age (AGA), and 103 (53.1%)
      were male. The amniotic fluid volume was reduced in 87 (44.8%) fetuses, and the
      umbilical artery Doppler revealed absence or inversion of diastolic flow in 122
      (62.9%) cases, and the analysis of the ductus venosus revealed abnormal flow in
      60 (34.8%) fetuses. The Hadlock formulae using three or four fetal biometric
      parameters had low absolute percentage error in the estimated fetal weight among
      preterm fetuses with abnormal Doppler studies who were born within 5 days of the
      ultrasound evaluation. The results were not influenced by the clinical and
      ultrasound parameters often found in early-onset placental insufficiency.
      CONCLUSION:  In this study, the formulae with the best performance for fetal
      weight estimation in the analyzed population were Hadlock I and IV, which use
      four and three fetal biometric parameters respectively to estimate the weight of
      preterm fetuses with abnormal Doppler studies.

PMID- 30235475
TI  - Meta-Analysis of Potent P2Y12-ADP Receptor Antagonist Therapy Compared to
      Clopidogrel Therapy in Acute Coronary Syndrome Patients with Chronic Kidney
      Disease.
AB  - BACKGROUND:  The clinical benefit of anti-platelet agents in patients with
      chronic kidney disease (CKD) is uncertain. In addition, the risk-benefit ratio of
      potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs),
      namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients
      suffering from acute coronary syndrome (ACS) remains unknown. OBJECTIVE:  We
      performed a meta-analysis of all studies comparing the clinical outcomes of PPA
      and clopidogrel therapy in CKD patients suffering from ACS. METHODS:  We searched
      PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the
      abstracts of international cardiology congresses from April 2000 to October 2017.
      Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were
      selected. Our literature research identified five studies which were included in
      the meta-analysis. The primary endpoint was a composite of major adverse
      cardiovascular events (MACEs) at the latest follow-up available. Secondary
      endpoint included bleedings. RESULTS:  We included data from three sub-group
      analysis of randomized clinical trials and two prospective observational studies
      (n = 31,234). Overall, PPAs were associated with lower rates of major
      cardiovascular events, with a pooled hazard ratio (pHR) of 0.88 (95% confidence
      interval [CI]: 0.79-0.99; p = 0.03), without increased bleedings (pHR = 1.10)
      (95% CI: 0.95-1.27; p = 0.18). In a sensitivity analysis restricted to studies
      enrolling invasively managed patients, the benefit of PPA on MACE was maintained
      (pHR = 0.85) (95% CI: 0.77-0.93; p < 0.001), including a reduction in mortality
      (pHR = 0.82) (95% CI: 0.7-0.96; p = 0.016). CONCLUSION:  Compared with
      clopidogrel, PPAs were associated with a reduced rate of MACE without increased
      bleedings in CKD patients with ACS. Among invasively managed patients, this
      benefit from PPA included a reduction in mortality.

PMID- 30235476
TI  - Platelet Reactivity and Early Outcomes after Transfemoral Aortic Valve
      Implantation.
AB  - Beyond thromboembolic events, peri-procedural bleeding remains one of the most
      frequent complications after transcatheter aortic valve implantation (TAVI). The
      majority of TAVI patients receive a dual anti-platelet treatment (DAPT) regimen.
      This analysis from the EVERY-TAVI register database aimed to analyse whether the
      level of on-treatment adenosine diphosphate-induced platelet reactivity predicts
      early outcomes at 30 days after TAVI. A total of 146 consecutive TAVI patients on
      DAPT who underwent platelet function testing with the Multiplate analyser were
      included here. Definition of bleeding events was done according to the Valve
      Academic Research Consortium-2 (VARC-2) classification. In our cohort, a status
      of low platelet reactivity (LPR, <= 18 units) was observed in 79 patients (54%),
      while high platelet reactivity (HPR, >= 46 units) was present in 18 patients
      (12%). At 30-day follow-up, the incidence of VARC-2 bleeds was 45.6% (n = 36) in
      LPR patients and 23.9% (n = 16) in patients without LPR (hazard ratio [HR] 2.10,
      95% confidence interval [CI], 1.17-3.79; p = 0.01). In age-adjusted multivariate
      analysis, a status of LPR was independently associated with VARC-2 bleeding
      events (HRadj, 2.06, 95% CI, 1.14-3.71; p = 0.02). HPR was not associated with
      the 30-day risk of death, stroke, or myocardial infarction (p >= 0.43). In
      summary, presence of LPR was associated with bleeding events in patients
      undergoing TAVI while presence of HPR was not associated with ischaemic outcomes
      at 30 days. The value of platelet function testing for bleeding risk prediction
      and for a possible guidance of anti-thrombotic treatment in the elderly TAVI
      population warrants further investigation.

PMID- 30235477
TI  - Macrophagic Stabilin-1 Restored Disruption of Vascular Integrity Caused by
      Sepsis.
AB  - Sepsis develops because of overwhelming inflammatory responses to bacterial
      infection, and disrupts vascular integrity. Stabilin-1 (STAB-1) is a phagocytic
      receptor, which mediates efferocytosis in a phosphatidylserine (PS)-dependent
      manner. STAB-1 is expected to play important roles in efferocytosis during
      sepsis. Here, we determined the role of STAB-1 in maintaining and restoring
      vascular integrity. Macrophages and vascular endothelial cells were used to
      assess the effect of STAB-1 on survival rate, phagocytic activity, vascular
      permeability and transendothelial migration (TEM). Additionally, we investigated
      whether the high-mobility group box 1 (HMGB1)-receptor for advanced glycated end
      products complex interfered with the binding of Stab1 to PS. Mortality rate was
      higher in the Stab1-knockout mice than in the wild-type mice, and STAB-1
      deficiency was related to reduced macrophage-mediated efferocytosis and the
      disruption of vascular integrity, which increased vascular permeability, and
      enhanced TEM. STAB-1 deficiency promoted lung injury, and elevated the expression
      of sepsis markers. The exogenous application of the anti-HMGB1 neutralizing
      antibody improved efferocytosis, vascular integrity and survival rate in sepsis.
      Collectively, our findings indicated that STAB-1 regulated and maintained
      vascular integrity through the clearance of infected apoptotic endothelial cells.
      Moreover, our results suggested that interventions targeting vascular integrity
      by STAB-1 signalling are promising therapeutic approaches to sepsis.

PMID- 30235479
TI  - Pro-Coagulant and Pro-Thrombotic Effects of Paclitaxel Mediated by Red Blood
      Cells.
AB  - BACKGROUND:  Paclitaxel is one of the most widely used anti-cancer drugs, but
      numerous case reports of thrombotic events in the cancer patients using
      paclitaxel raise concern over its pro-thrombotic risk. MATERIALS AND METHODS:  We
      investigated whether paclitaxel can elicit pro-thrombotic properties in red blood
      cells (RBCs) through phosphatidylserine (PS) exposure and microvesicle (MV)
      release. RESULTS:  In freshly isolated human RBCs, paclitaxel induced thrombin
      generation through PS exposure and MV release, whereas either coagulation factors
      or platelets were unaffected. Paclitaxel-induced PS exposure in RBC was mediated
      by scramblase activation which was induced by calcium-independent protein kinase
      C (PKC)zeta activation. Paclitaxel also increased RBC-endothelial cell adhesion
      and RBC aggregate formation which can also contribute to thrombosis. Indeed,
      intravenous administration of paclitaxel to rats induced PS exposure and PKCzeta
      activation in RBCs in vivo which ultimately promoted venous thrombus formation.
      CONCLUSION:  These results demonstrated that paclitaxel may elicit pro-thrombotic
      properties in RBCs through PS exposure and MV release, which can ultimately
      promote thrombus formation.

PMID- 30235478
TI  - Relapse Rate in Survivors of Acute Autoimmune Thrombotic Thrombocytopenic Purpura
      Treated with or without Rituximab.
AB  - BACKGROUND:  Autoimmune thrombotic thrombocytopenic purpura (iTTP) is caused by
      autoantibody-mediated severe a disintegrin and metalloprotease with
      thrombospondin type 1 repeats, member 13 (ADAMTS13) deficiency leading to micro
      angiopathic haemolytic anaemia (MAHA) and thrombocytopenia with organ damage.
      Patients survive with plasma exchange (PEX), fresh frozen plasma replacement and
      corticosteroid treatment. Anti-CD20 monoclonal antibody rituximab is increasingly
      used in patients resistant to conventional PEX or relapsing after an acute bout.
      OBJECTIVE:  This retrospective observational study focused on the relapse rate
      and possible influencing factors including treatment with rituximab first
      introduced in 2003. PATIENTS AND METHODS:  Seventy patients treated between
      January 2003 and November 2014 were evaluated. Number, duration, clinical
      manifestations, laboratory data and treatment of acute episodes were documented.
      Diagnostic criteria of acute iTTP were thrombocytopenia, MAHA, increased lactate
      dehydrogenase and severe ADAMTS13 deficiency. RESULTS:  Fifty-four female and 16
      male patients had a total of 224 acute episodes over a median observation period
      of 8.3 years. The relapse rate was 2.6% per month, for women 2.4% and for men
      3.5% per month. Since 2003, 17 patients with a first iTTP episode were treated
      with rituximab, whereas 28 were not. There was a trend towards lower relapse
      rates after rituximab treatment over the ensuing years. However, this was
      statistically not significant. CONCLUSION:  This analysis does not show a
      significant reduction of acute iTTP relapses by rituximab given during an acute
      bout. Initial episodes are characterized by more severe clinical signs compared
      with the less severe relapses. Furthermore, men suffer significantly more
      frequent and considerably more serious acute relapses.

PMID- 30235481
TI  - Pro-Angiogenic Effects of Latent Heparanase and Thrombin Receptor-Mediated
      Pathways-Do They Share a Common Ground in Melanoma Cells?
AB  - Heparanase (HPSE) is an endo-beta-D-glucuronidase that cleaves heparan sulphate
      (HS) chains of proteoglycans (HSPGs). Besides a remodelling of the extracellular
      matrix, HPSE increases the bioavailability of pro-angiogenic mediators, such as
      HS-associated vascular endothelial growth factor (VEGF), thereby contributing to
      metastatic niche formation. Notably, HPSE also induces release of VEGF from
      tumour cells independent of its enzymatic activity, but the underlying molecular
      mechanisms remain unresolved. We found that exogenous addition of latent HPSE
      stimulates VEGF release from human MV3 melanoma cells. The same effect was noted
      upon direct stimulation of thrombin receptor (protease-activated receptor 1 [PAR
      1]) by Thrombin Receptor Activator Peptide 6 (TRAP-6). The matricellular ligand
      cysteine-rich 61 protein (Cyr61) was identified as pathway component since Cyr61
      knockdown in MV3 cells abolished the VEGF release by TRAP-6 and HPSE. Since both
      TRAP-6 and HPSE mediated an up-regulation of phosphorylated focal adhesion
      kinase, which could be blocked by antagonizing PAR-1, we postulated a crosstalk
      between latent HPSE and PAR-1 in promoting pro-angiogenic pathways. To test this
      hypothesis at a molecular level, we applied dynamic mass redistribution (DMR)
      technique measuring intracellular mass relocation as consequence of direct
      receptor activation. Indeed, latent HPSE evoked a concentration-dependent DMR
      signal in MV3 cells as TRAP-6 did. Both could be modulated by targeting G-protein
      receptor signalling in general or by the PAR-1 inhibitor RWJ 56110. Using cells
      devoid of cell surface HS synthesis, we could confirm HPSE effects on PAR-1,
      independent of HSPG involvement. These data indicate, for the first time, a
      crosstalk between latent HPSE, thrombin receptor activation and G-protein
      signalling in general.

PMID- 30235480
TI  - Proteasome Inhibition with Bortezomib Induces Apoptosis of Long-Lived Plasma
      Cells in Steroid-Resistant or Relapsed Immune Thrombocytopaenia.
AB  - Primary immune thrombocytopaenia (ITP) is the most common haemorrhagic disease.
      Although most patients respond initially to mainstream therapies, such as
      corticosteroids, immunosuppressants or rituximab, a large proportion of patients
      fail to respond or relapse. These treatments only affect B lymphocytes or short
      lived plasma cells, but not already existing long-lived plasma cells (LLPCs)
      which persistently secrete antibodies. We hypothesized that LLPCs may play a role
      in the corticosteroid-resistant or relapsed ITP patients, and bortezomib, a
      proteasome inhibitor, may act on plasma cells and offer a therapeutic effect.
      Although a significant difference in the proportion of CD19-CD38hiCD138+ total
      LLPCs was not observed by flow cytometry, a glycoprotein (GP) IIb/IIIa-specific
      enzyme-linked immunosorbent spot (ELISpot) assay of sorted CD19-CD138+ LLPCs
      confirmed the existence of anti-platelet antibody-secreting LLPCs in ITP patients
      in contrast to healthy controls. Moreover, the LLPCs could be eliminated in the
      presence of bortezomib by ELISpot assay, which was also confirmed by flow
      cytometry. Accordingly, a modified monoclonal antibody immobilization of platelet
      antigen assay of sorted CD19-CD138+ LLPCs revealed that the concentration of anti
      platelet antibodies decreased remarkably when cultured with 0.25 ng/mL bortezomib
      for 5 days. The apoptosis assay demonstrated that bortezomib could induce
      apoptosis of LLPCs in a concentration-dependent manner. The proteasome activity
      assay showed that bortezomib significantly reduced the proteasome activity in
      sorted CD19-CD138+ LLPCs. Furthermore, in active ITP murine models, bortezomib
      eliminated LLPCs in vivo and alleviated thrombocytopaenia. We conclude that LLPCs
      participate in the pathogenesis of ITP and bortezomib may have potential as a
      novel therapeutic regimen.

PMID- 30235482
TI  - The First Intrinsic Tenase Complex Inhibitor with Serine Protease Structure
      Offers a New Perspective in Anticoagulant Therapy.
AB  - Components of the intrinsic blood coagulation pathway, among them factor VIIIa
      (FVIIIa), have been recognized as suitable therapeutic targets to treat venous
      thromboembolism, pathological process behind two very serious cardiovascular
      diseases, deep vein thrombosis and pulmonary embolism. Here, we describe a unique
      glycoprotein from the nose-horned viper (Vipera ammodytes ammodytes [Vaa]) venom,
      Vaa serine proteinase homolog 1 (VaaSPH-1), structurally a serine protease but
      without an enzymatic activity and expressing potent anticoagulant action in human
      blood. We demonstrated that one of its targets in the blood coagulation system is
      FVIIIa of the intrinsic tenase complex, where it antagonizes the binding of FIXa.
      Anticoagulants with such characteristics are intensively sought, as they would be
      much safer for medical application as the contemporary drugs, which frequently
      induce excessive bleeding and other complications. VaaSPH-1 is unlikely to be
      orally available for chronic usage as it has molecular mass of 35 kDa. However,
      it represents a very promising template to design low molecular mass FVIIIa
      directed anticoagulant substances, based on structural features of the
      interaction surface between VaaSPH-1 and FVIIIa. To this end, we constructed a
      three-dimensional model of VaaSPH-1 bound to FVIIIa. The model exposes the 157
      loop and the preceding alpha-helix as the most appropriate structural elements of
      VaaSPH-1 to be considered as a guideline to synthesize small FVIIIa-binding
      molecules, potential new generation of anticoagulants.

PMID- 30235483
TI  - Anti-ADAMTS13 Autoantibodies against Cryptic Epitopes in Immune-Mediated
      Thrombotic Thrombocytopenic Purpura.
AB  - Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by
      severe ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1
      repeats, member 13) deficiency, the presence of anti-ADAMTS13 autoantibodies and
      an open ADAMTS13 conformation with a cryptic epitope in the spacer domain
      exposed. A detailed knowledge of anti-ADAMTS13 autoantibodies will help
      identifying pathogenic antibodies and elucidating the cause of ADAMTS13
      deficiency. We aimed at cloning anti-ADAMTS13 autoantibodies from iTTP patients
      to study their epitopes and inhibitory characteristics. We sorted anti-ADAMTS13
      autoantibody expressing B cells from peripheral blood mononuclear cells of 13
      iTTP patients to isolate anti-ADAMTS13 autoantibody sequences. Ninety-six B cell
      clones producing anti-ADAMTS13 autoantibodies were identified from which 30
      immunoglobulin M (IgM) and 5 IgG sequences were obtained. For this study, we only
      cloned, expressed and purified the five IgG antibodies. In vitro characterization
      revealed that three of the five cloned IgG antibodies, TTP73-1, ELH2-1 and
      TR8C11, indeed recognize ADAMTS13. Epitope mapping showed that antibodies TTP73-1
      and TR8C11 bind to the cysteine-spacer domains, while the antibody ELH2-1
      recognizes the T2-T3 domains in ADAMTS13. None of the antibodies inhibited
      ADAMTS13 activity. Given the recent findings regarding the open ADAMTS13
      conformation during acute iTTP, we studied if the cloned antibodies could
      recognize cryptic epitopes in ADAMTS13. Interestingly, all three antibodies
      recognize cryptic epitopes. In conclusion, we cloned three anti-ADAMTS13
      autoantibodies from iTTP patients that recognize cryptic epitopes. Hence, these
      data nicely fit our recent finding that the conformation of ADAMTS13 is open
      during acute iTTP.

PMID- 30235484
TI  - Apixaban Interacts with Haemoglobin: Effects on Its Plasma Levels.
AB  - The direct oral anticoagulant apixaban (APX), a strong factor Xa inhibitor, binds
      also to plasma proteins, especially albumin, and minimally to alpha1-acid
      glycoprotein. Although APX can cross the red cell membrane, due to its chemical
      structure, and could bind to haemoglobin (Hb), no investigation was performed on
      this possible phenomenon that could affect the APX plasma concentration and thus
      its pharmacokinetics and pharmacodynamics. We addressed this issue by (1)
      measuring the levels of APX and haematological/biochemical parameters in 90
      patients on APX therapy; (2) assessing the effect of APX on oxygen saturation
      curves of Hb; (3) testing the direct APX binding to Hb by fluorescence
      spectroscopy and a zinc-induced precipitation of Hb coupled to a reversed-phase
      high-performance liquid chromatography (HPLC)-based method; and (4) simulating in
      silico by molecular docking the APX interaction with human Hb. In a multivariable
      analysis, Hb was the only independent variable significantly and inversely
      associated in 90 patients with APX peak plasma level, at variance with patients
      treated with rivaroxaban (n = 86) and dabigatran (n = 34) therapy. APX causes a
      progressive left-shift of the oxygen dissociation curve of purified Hb solution,
      with a Kd ?300 uM. Fluorescence- and HPLC-based assays concordantly showed that
      APX binds to Hb with a Kd ?350 uM. Finally, docking simulations showed that APX
      can fit into in the central cavity of Hb. These findings support the hypothesis
      that APX does bind to Hb, which, due to its millimolar concentration in blood,
      can act as 'buffer' for the drug and consequently affect its free plasma level.

PMID- 30235485
TI  - Docking of Meprin alpha to Heparan Sulphate Protects the Endothelium from
      Inflammatory Cell Extravasation.
AB  - Pulmonary arterial hypertension (PAH) is a rare disease characterized by
      increased pulmonary pressure and vascular remodelling as a consequence of smooth
      muscle cell proliferation, endothelial cell dysfunction and inflammatory
      infiltrates. Meprin alpha is a metalloproteinase whose substrates include
      adhesion and cell-cell contact molecules involved in the process of immune cell
      extravasation. In this study, we aimed to unravel the role of meprin alpha in PAH
      induced vascular remodelling. Our results showed that meprin alpha was present in
      the apical membrane of endothelial cells in the lungs and pulmonary arteries of
      donors and idiopathic PAH (IPAH) patients. Elevated circulating meprin alpha
      levels were detected in the plasma of IPAH patients. In vitro binding assays and
      electron microscopy confirmed binding of meprin alpha to the glycocalyx of human
      pulmonary artery endothelial cells (hPAECs). Enzymatic and genetic approaches
      identified heparan sulphate (HS) as an important determinant of the meprin alpha
      binding capacity to hPAEC. Meprin alpha treatment protected from excessive
      neutrophil infiltration and the protective effect observed in the presence of
      neutrophils was partially reversed by removal of HS from hPAEC. Importantly, HS
      levels in pulmonary arteries were decreased in IPAH patients and binding of
      meprin alpha to HS was impaired in IPAH hPAEC. In summary, our results suggest a
      role of HS in docking meprin alpha to the endothelium and thus in the modulation
      of inflammatory cell extravasation. In IPAH, the decreased endothelial HS results
      in the reduction of meprin alpha binding which might contribute to enhanced
      inflammatory cell extravasation and potentially to pathological vascular
      remodelling.

PMID- 30235487
TI  - Venous Thrombosis Risk after Arthroscopy of the Knee: Derivation and Validation
      of the L-TRiP(ascopy) Score.
AB  - Patients at high risk for venous thrombosis (VT) following knee arthroscopy could
      potentially benefit from thromboprophylaxis. We explored the predictive values of
      environmental, genetic risk factors and levels of coagulation markers to
      integrate these into a prediction model. Using a population-based case-control
      study into the aetiology of VT, we developed a Complete (all variables),
      Screening (easy to use in clinical practice) and Clinical (only environmental
      risk factors) model. The Clinical model was transformed into the Leiden
      Thrombosis Risk Prediction (arthroscopy) score [L-TRiP(ascopy) score]. Model
      validation was performed both internally and externally in another case-control
      study. A total of 4,943 cases and 6,294 controls were maintained in the analyses,
      107 cases and 26 controls had undergone knee arthroscopy. Twelve predictor
      variables (8 environmental, 3 haemorheological and 1 genetic) were selected from
      52 candidates and incorporated into the Complete model (area under the curve
      [AUC] of 0.81, 95% confidence interval [CI], 0.76-0.86). The Screening model (9
      predictors: environmental factors plus factor VIII activity) reached an AUC of
      0.76 (95% CI, 0.64-0.88) and the Clinical (and corresponding L-TRiP(ascopy))
      model an AUC of 0.72 (95% CI, 0.60-0.83). In the internal and external
      validation, the Complete model reached an AUC of 0.78 (95% CI, 0.52-0.98) and
      0.75 (95% CI, 0.42-1.00), respectively, while the other models performed slightly
      less well.

PMID- 30235488
TI  - Early Retinal Findings Following Cooling in Neonatal Encephalopathy.
AB  - BACKGROUND AND AIM:  Perinatal HI (hypoxia-ischemia)-related visual defects
      including blindness are known to be associated with ischemic lesions in
      intracerebral visual pathways and ischemic retinal damage (IRD). Intraocular
      hemorrhages (IOH) such as retinal hemorrhage (RH), which may result from
      perinatal HI, can cause IRD by various mechanisms. We aimed to evaluate the early
      retinal findings in neonates with moderate-to-severe neonatal encephalopathy (NE)
      who underwent TH and its relationship between coagulation status, amplitude
      integrated electroencephalography (aEEG) patterns, and magnetic resonance imaging
      magnetic resonance spectroscopy (MRI-MRS) findings. METHOD AND PATIENTS:  A total
      of 31 newborn infants who underwent moderate-to-severe NE and TH included in the
      study. Coagulation parameters were taken immediately before starting TH, and
      daily during TH period. aEEG records were obtained during TH and rewarming
      period.Binocular indirect ophthalmoscopic examination (BIOE) and MRI-MRS scanning
      were performed when TH protocol completed. RESULTS:  Total 13 (41.9%) patients
      had abnormal BIOE findings. Ten of them were (77%) IOH, other findings are as
      follows: RH (n = 7), optic disc hemorrhage (n = 2), and vitreous hemorrhage (n =
      1). Initial coagulation status was not related to IOH. Worsened aEEG and MRI-MRS
      results were not related to BIOE findings. CONCLUSION:  Frequency of IOH is high
      in newborns with NE who underwent TH being independent from severity of MRS-MRI
      findings, aEEG pattern, and disturbed coagulation status.

PMID- 30235486
TI  - Patient-Reported Treatment Satisfaction with Dabigatran versus Warfarin in
      Patients with Non-Valvular Atrial Fibrillation in China.
AB  - BACKGROUND:  Anti-coagulant therapy satisfaction for patients with atrial
      fibrillation is a critical issue, which impacts on their treatment adherence and
      clinical outcomes. The disadvantages of long-term warfarin treatment are well
      described, and novel oral anti-coagulants have become an alternative option.
      MATERIALS AND METHODS:  We compared patient-reported treatment satisfaction with
      dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients in
      China. Treatment satisfaction was assessed using the Anti-Clot Treatment Scale
      (ACTS) questionnaire, which included a 12-item ACTS Burdens scale and a 3-item
      ACTS Benefits scale. RESULTS:  Among 834 patients, 246 patients (29.5%) were
      taking dabigatran and the others were on warfarin. Propensity score matching was
      employed to identify 182 patient pairs with balanced baseline characteristics.
      The global ACTS Burdens score and the global ACTS Benefits score were comparable
      between the dabigatran and warfarin groups (44.86 +/- 3.95 vs. 44.28 +/- 3.51, p
      = 0.423; 11.49 +/- 2.92 vs. 11.42 +/- 3.03, p = 0.194, respectively). The monthly
      cost of dabigatran was significantly higher compared with that of warfarin due to
      a lack of insurance coverage (USD 176.78 +/- 9.15 vs. USD 2.49 +/- 0.76, p =
      0.000). The discontinuation rate of dabigatran was significantly higher than
      warfarin at the 6-month follow-up (33.5% vs. 19.2%, p = 0.003). Adjusted logistic
      regression showed that dabigatran was associated with a significant greater odds
      of non-persistence (odds ratio: 2.13, 95% confidence interval: 1.27-3.59, p =
      0.004). CONCLUSION:  Dabigatran therapy in patients with NVAF in China associated
      with no improvement in satisfaction and a higher discontinuation rate compared
      with warfarin therapy largely due to increased economic burden.

PMID- 30235489
TI  - Late Presentation of a Duodenal Obstruction in a Child with Failure to Thrive and
      Abdominal Pain.

PMID- 30235490
TI  - [Pitfalls in the Diagnosis of Diabetes: Are we too Lax with Laboratory
      Parameters?]
AB  - The diagnosis of diabetes is associated with pre-analytical and analytical
      problems. Fasting glucose (FG), oral glucose tolerance test (oGTT) and HbA1c have
      advantages and shortcomings and have no equal diagnostic validity. oGTT is the
      most sensitive test, but its reproducibility is rather poor (CV+/- 15 %). FG
      detects only 70 - 80 % of overt diabetes. FG is falsified by inappropriate blood
      sampling, intra-individual fluctuations and mistakes with the oGTT. HbA1c despite
      IFC- standardization, but with a tolerable coefficient of variation of +/- 18 %
      in round robin tests and use of not commutable control material is not easy to
      interpret. HbA1c analysis shows also interferences and is therefore of limited
      diagnostic value. Its threshold value of >= 6.5 % (>= 48 mmol/mol Hb) is based on
      consensus and not on evidence. The diagnostic effort (FG and/or oGTT+HbA1c) with
      serious consequences is minimal invasive, reasonable and cheap. It prevents over-
      and underdiagnosis.

PMID- 30235492
TI  - Changes in Serum Immunoglobulin G4 Levels in Patients with Newly Diagnosed
      Graves' Disease.
AB  - OBJECTIVE: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune
      mediated condition that can affect almost any organ. We investigated the
      association between IgG4-RD and the main characteristics of Graves' disease (GD)
      at the time of diagnosis. Additionally, we evaluated whether serum IgG4 levels
      change during treatment. DESIGN AND PATIENTS: Twenty-eight patients with newly
      diagnosed GD were enrolled into this longitudinal follow-up study. Serum IgG4
      levels and thyroid function were measured in all the participants at the time of
      diagnosis. Further, the serum IgG4 levels of nine of 28 patients with untreated
      GD were measured after the achievement of euthyroid state (through the use of
      methimazole). RESULTS: Two (7.1%) of 28 patients with untreated GD had elevated
      serum IgG4 levels of >135 mg/dL. There was no significant difference in the
      average IgG4 levels before and after the achievement of euthyroid state (66.2+/
      74.0 mg/dL vs. 50.5+/-47.3 mg/dL). In two patients, the elevated serum IgG4
      levels returned to normal after treatment. However, one patient had an elevated
      serum IgG4 level of 136.6 mg/dL after treatment. CONCLUSIONS: This study showed
      that serum IgG4 levels varied with treatment in patients with GD, independent of
      thyroid function, suggesting that IgG4 might be indirectly related to GD.

PMID- 30235491
TI  - Changes in Oxidized Low-Density Lipoprotein Rather Than in Paraoxonase1 are
      Associated with Changes in the Leptin/Leptin Receptor Ratio in Obese Children
      During Weight-Loss Therapy.
AB  - BACKGROUND: Oxidative stress and impaired production of adipokines in childhood
      obesity contribute to the development of obesity-related disorders. We assessed
      whether weight loss after lifestyle intervention alters biomarkers of
      oxidant/antioxidant status, and whether these alterations are associated with
      changes in anthropometric parameters and adipokines in obese children. MATERIALS
      AND METHODS: We determined oxidized low-density lipoprotein (ox-LDL), anti ox
      LDL, paraoxonase1 (PON1), leptin, soluble leptin receptor (sOB-R), total
      adiponectin, high molecular weight adiponectin concentrations and body
      composition (by dual-energy X-ray absorptiometry) in 60 prepubertal obese
      children (Body Mass Index, BMI Z-score>2) before and after a 3-month
      intervention. The control group consisted of 44 non-obese children (BMI Z-score<
      1+1>). RESULTS: Ox-LDL, ox-LDL/LDL, and anti ox-LDL concentrations as well as
      leptin to sOb-R ratio were reduced (p<0.001; p=0.018; p<0.001; p<0.001,
      respectively) in obese children with weight loss (BMI Z-score change<=-0.5) after
      a 3-month therapy. These parameters were stable in the obese group without weight
      loss (BMI Z-score change>-0.5). Changes in ox-LDL and PON1 levels in all obese
      children correlated positively with changes in the leptin to sOB-R ratio
      (r=0.400, p=0.002; r=0.304, p=0.028, respectively). After adjustment for changes
      in BMI Z-score in the multivariate regression model, the association between the
      changes in ox-LDL levels and changes in the leptin/sOb-R ratio remained
      statistically significant (beta=0.184, p=0.014). CONCLUSIONS: We found out that a
      3-month lifestyle intervention associated with weight loss improves the
      oxidant/antioxidant balance and promotes anti-atherogenic changes in prepubertal
      obese children in a way dependent on the alterations in the leptin to sOB-R
      ratio.

PMID- 30235493
TI  - Altered TEG Parameters Identify Hypercoagulablilty and are of Diagnosis Value for
      Papillary Thyroid Carcinoma Patients.
AB  - OBJECTIVE: The goal of this study was to clarify the changes and clinical
      significance of thromboelastography (TEG) parameters in papillary thyroid
      carcinomas and nodular goiters. METHODS: 62 nodular goiter (NG) patients and 53
      papillary thyroid carcinoma (PTC) patients were included. Coagulation indicators,
      together with a series of TEG parameters were collected and analyzed, compared
      with results of 61 healthy controls (HC). Correlation analysis was conducted
      between routine coagulation indicators and TEG parameters. ROC curves were used
      to evaluate the potential diagnosis value of the TEG parameters that were altered
      in papillary thyroid carcinoma patients. RESULTS: APTT and PT in papillary
      thyroid carcinoma group were statistically significant higher than that in
      control group (p<0.05). MPV was found to be higher in PTC than NG and healthy
      controls.R, K and SP levels were significantly lower in PTC group than that in HC
      group; Angle, CI and TPI levels were significantly higher in PTC group than that
      in HC group. Areas under the ROC curve of CI, TPI, and angle were 0.725, 0.714,
      and 0.687 for distinguishing PTC from HC, 0.662, 0.668 and 0.591 for
      distinguishing PTC from NG. CONCLUSION: TEG parameters are altered and indicate
      hypercoagulablilty status of papillary thyroid carcinoma patients; CI, TPI, and
      angle could be potential diagnosis indicators for detecting papillary thyroid
      carcinoma.

PMID- 30235494
TI  - Lipid Level Related with Osteoporosis in Type 2 Diabetes Patients.
AB  - OBJECTIVE: Osteoporosis is a systemic skeletal disorder characterizedby reduced
      bone mass, deteriorated bone structure. Various studies have tried to evaluate
      the association between lipid level and osteoporosis, but the results were proved
      to be controversial. The objectives of this study are to assess the correlation
      between BMD and serum lipid levels, to determine independent variables associated
      with osteoporosis and osteopenia in men and postmenopausal women with type 2
      diabetes (T2D). MATERIALS AND METHODS: All participants of the study were carried
      out biochemical analysis of blood and the analysis of the lipid profile that
      included total cholesterol (TC) and triglyceride (TG). Physical examination and
      dual-energy X-ray absorptiometry examination were performed. Multiple linear
      regression and multivariate logistic regression were used to evaluate
      associations between serum TC and TG levels and the osteoporosis or osteopenia.
      RESULTS: The level of serum TG was directly correlated with BMD at the lumbar
      spine in all patients in multiple linear regression models. After adjusting for
      potential confounding factors, decreased level of serum TG was independent risk
      factor for osteoporosis(p=0.022) in T2D patients. It also showed that a greater
      BMI was protective factor for osteoporosis (p=0.019) and lower level of beta-CTX
      was an independent risk factor for osteopenia (p=0.008) and osteoporosis
      (p=0.001) in T2D patients. CONCLUSION: Among Chinese patients with type 2
      diabetes, the decreased level of serum TG might indicate a risk of osteoporosis.
      Further research is needed to confirm the finding and to clarify the
      contradictions identified.

PMID- 30235495
TI  - Metastatic Phaeochromocytoma: Spinning Towards More Promising Treatment Options.
AB  - Phaeochromocytomas (PCC) and paragangliomas (PGL) are rare tumours arising from
      the chromaffin cells of the adrenal medulla (PCC) or the paraganglia located
      outside the adrenal gland (PGL). However, their incidence is likely to be
      underestimated; around 10% of all PCC/PGL are metastatic, with higher metastatic
      potential of PGLs compared to PCCs. If benign, surgery is the treatment of
      choice, but if metastatic, therapy is challenging. Here we review the currently
      existing therapy options for metastatic PCCs/PGLs including conventional
      chemotherapy (the original Averbuch scheme, but updated), radiopharmaceutical
      treatments (131I-MIBG, 90Y- and 177Lu-DOTATATE) and novel targeted therapies
      (anti-angiogenic tyrosine kinase inhibitors and mTORC1 inhibitors), emphasising
      future therapeutic approaches (HIF-2alpha and PARP inhibitors, temozolomide
      alone, metronomic temozolomide, somatostatin analogues) based on the oncogenic
      signalling pathways related to three different clusters comprising more than 20
      well-characterised PCC/PGL susceptibility genes. We suggest that targeted
      combination therapies including repurposed agents may offer more effective future
      options worthy of exploration.

PMID- 30235496
TI  - Comparing Schizophrenia Patients With a Predicted High/Low Risk of Nonresponse
      Receiving Treatment with Ziprasidone and Haloperidol: A Randomized-Controlled
      Study.
AB  - INTRODUCTION: The aim of this double-blind randomized study was to evaluate the
      response to antipsychotic treatment in schizophrenia patients with predicted
      high/low risk of nonresponse identified by applying a set of well-established
      scales and predictors of outcome and to compare efficacy between ziprasidone and
      haloperidol. METHODS: One hundred twelve schizophrenia patients (ziprasidone:
      n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome
      Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale
      (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus
      Scale (SAS), and Hillside Akathisia Scale (HAS). RESULTS: Ninety-two patients
      (82%) were predicted to have a high risk of nonresponse. No significant
      difference regarding PANSS improvement in this subsample was found comparing
      ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no
      significant difference was found regarding the course of the PANSS total score,
      GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol.
      Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011).
      DISCUSSION: An alarmingly high number of patients were at high risk of
      nonresponse to antipsychotic treatment.

PMID- 30235497
TI  - [Quantitative Analysis for Levocetirizine Hydrochloride Tablets Based on NIR
      Spectroscopy].
AB  - The aim of this study was to develop a quantitative analytical method to measure
      the effective components in the left cetirizine hydrochloride tablets using near
      infrared spectroscopy combining with a partial least square (PLS) analysis model.
      The method was internal cross-validated to determine the best wavelength range,
      spectral preprocessing methods and the optimal number of principal components.
      The concentration of validation set samples was predictable by PLS model. The
      RMSECV value was 0.276, and the R(2) value was 0.974. Our study suggests that
      this model can be used for rapid quantitative analysis of left cetirizine
      hydrochloride tablets from different manufacturers.

PMID- 30235498
TI  - [Rapid Determination of Pinoresinol Diglucoside and Geniposidic Acid in Eucommia
      ulmoides with Near Infrared Spectroscopy Combined with Chemometrics Methods].
AB  - To develop a quantitative models for simultaneous determination of pinoresinol
      diglucoside (PDG) and geniposidic acid (GPA) in Eucommia ulmoides with near
      infrared (NIR) spectroscopy combined with chemometrics. The NIR spectra were
      collected in diffuse reflection mode and pretreated with various spectra
      preprocessing methods including first-order differentiator, multiplicative
      scatter correction and so on. The optimal wavelength variables were screened out
      by competition adaptive weighted sampling method. The quantitative models for the
      simultaneous determination of PDG and GPA in Eucommia ulmoides were established
      with partial least squares (PLS) algorithm and cross validation methods. The
      quantitative prediction models for simultaneous determination of PDG and GPA in
      Eucommia ulmoides showed good predictive ability. The correlation coefficients
      (R(2)) of the two calibration models were 0.961 5, 0.958 3 while the roots mean
      square of cross-validation (RMSECV) were 0.001 5, 0.006 4, respectively. The
      quantitative prediction models proved that near infrared spectra method used for
      the quantitative analysis of PDG and GPA in Eucommia ulmoides owned high
      prediction accuracy and can meet the precision need of rapid determinations of
      PDG and GPA in Eucommia ulmoides in reality so t it provides a new method to
      realize the real time on line of quality control of Eucommia ulmoides.

PMID- 30235499
TI  - History of Korean Spinal Neurosurgery Society.

PMID- 30235500
TI  - [The Research of Spatial Heterodyne Raman Spectroscopy with Standoff Detection].
AB  - Spatial heterodyne Raman spectroscopy (SHRS) is a new type of Raman spectroscopic
      detection technique with characteristics of high optical throughout, high
      spectral resolution, and no moving parts. SHRS is very suitable for the planetary
      exploration missions, which can be used to the analysis of minerals and find the
      biomarkers maybe exist on the surface of planetary. The authors have applied the
      technique to the standoff Raman spectroscopic detection, analyzed the main
      characteristics, including spectral resolution, bandpass and signal to noise
      (SNR), of standoff SHRS and proved it through experiments. The basic theory of
      standoff SHRS has been described briefly while a breadboard has been designed,
      built and calibrated. On the basis, the Raman spectra of some inorganic solids,
      organic liquids and some natural minerals have been achieved at a distance of 10
      m, the SNR of the breadboard has been estimated. Due to the poor adjustment and
      the defects of the optical elements, the breadboard is far away from an ideal
      system. But the results show that the SNR is better than 5 for most of the main
      Raman peaks of the samples, which can meet the basic requirement of clear
      positive detection of typical Raman peaks and the feasibility of standoff SHRS
      has been proved. SHRS can overcome the main defects of dispersive grating Raman
      spectrometers and Fourier transform Raman spectrometers and it has a great
      application prospect on the detection and analysis of the planetary surface. The
      work of the authors can prove the potentiality of SHRS on standoff detection and
      can provide reference for the engineering realization of standoff SHRS.

PMID- 30235501
TI  - [Confocal Raman Spectroscopy Method Based on Quadratic Curve Fitting].
AB  - Raman spectroscopy plays an improtant role in analytical science because of its
      unique characteristics, such as non-contact and non-destructive detecting, fewer
      sample consumption, high sensitivity and other characteristics, and it provides a
      powerful analytical tool for the modern basic research fields. Because of the
      combination of confocal microscopy technology and Raman spectroscopy technology,
      confocal Raman microscopy has the advantage of both high resolution spectroscopy
      and chromatography detection, which inherits from confocal microscopy and raman
      spectroscopy. As a result, it is widely used in many fields, such as physical
      chemistry, materials science, biomedical, archaeological, cultural
      identification, and forensic science. But with the environmental changing, the
      system drifting or other issues, during the long detection process, the system
      turns to defocusing. As a result, during the hole scanning process, the system
      can not be focused on every detection point, and then it would lead to a mistake.
      Eventurally, conventional confocal Raman system could obtain the presence of
      measurement error even erroneous results in the long process. In this paper, on
      the basis of conventional confocal Raman system, a confocal Raman spectroscopy
      method based on quadratic curve fitting is proposed to solve this problem. Based
      on the principle that the maxium of the concal curve corresponding the system
      foucs, the steps to find system foucus as follows: fist, usesing quadratic curve
      to fit confocal curve; second, finding the maxium of the confocal curve; and last
      obtaining the system foucs. With this method, during the scanning process, every
      point should be focused, therefore, the effect of defocusing is eliminated
      efficiently, and accurate measurements of confocal Raman spectroscopy system is
      achieved. Through simulation and experimental results show that: the proposed
      method that confocal Raman spectroscopy method based on quadratic curve fitting
      can effectively eliminate the influence of system defocus on experimental result,
      and effectively improve the axial system of fixed focus accuracy, which could
      provide a guarantee for further application of confocal Raman spectroscopy. This
      anti-drift method is effective and accurate in focusing with great potential to
      be applied in broader areas.

PMID- 30235502
TI  - [Surfaced-Enhanced Raman Scattering Spectroscopic Study on Sheng-Di-Dang-Gui
      Decoction].
AB  - To reveal the relationship between the single decoction and prescription, the
      surface-enhanced Raman scattering (SERS) spectroscopy of Sheng-Di-Dang-Gui
      decoction (SDDGD), Sheng-Di decoction (SDD) and Dang-Gui decoction (DGD) were
      tested and analyzed. Mainly seventeen Raman signals (538, 622, 732, 761, 835,
      876, 959, 1 145, 1 245, 1 276, 1 326, 1 402, 1 456, 1 470, 1 518, 1 546 and 1 605
      cm(-1)) in three decoctions were discussed. The characteristic Raman bands of
      three decoctions were tentatively assigned. Fifteen obvious Raman bands (538,
      732, 761, 835, 876, 959, 1 145, 1 245, 1 276, 1 326, 1 402, 1 456, 1 470, 1 518
      and 1 605 cm(-1)) were observed in the SERS spectroscopy of SDDGD, thirteen
      obvious Raman bands (538, 761, 835, 876, 959, 1 145, 1 245, 1 276, 1 326, 1 402,
      1 470, 1 518 and 1 546 cm(-1)) were observed in the SERS spectroscopy of SDD, ten
      obvious Raman bands (538, 622, 732, 761, 835, 876, 959, 1 245, 1 326 and 1 402
      cm(-1)) were observed in the SERS spectroscopy of DGD. Some Raman bands in SERS
      spectra of SDD and DGD were retained in the SDDGD, however some Raman bands in
      two kinds of decoctions never appeared in the SDDGD. And new Raman bands (1 456
      and 1 605 cm(-1)) were generated in the SDDGD, resulted in the fact that new
      chemical compositions were created. Medical ingredients in the SDDGD were not the
      simple addition of SDD and DGD. The results showed that the SERS spectroscopy
      might provide a new kind of novel, effective and simple detecting method for the
      prescription research.

PMID- 30235503
TI  - [Study on Line CARS for Temperature Measurement in Combustion Flow Field].
AB  - Some laser beams meet at a single point by a convex len in normal coherent anti
      Stokes Raman scattering (CARS), and the CARS signal with temperature information
      of the focal piont yields under phase matching. Normal CARS can only get the
      temperature of one spatial piont in one measurement, which can not meet the needs
      of deep research on combustion flow field. In order to get more information in
      one test and improve the measuring capacity of CARS, line CARS (L-CARS) was
      presented. In L-CARS, convex lens are replaced by cylindrical convex lens to get
      a focal line, and nearly all the points on the line meet the phase matching. So,
      the CARS signal of each point on the line yield in one test. Cylindrical convex
      lens are also used in subsequent beam path to focus the CARS signals into
      spectrometer, and ICCD camera transfers the signals to computer to acquire the
      temperature of each point. Then, the measuring capacity of CARS is advanced from
      piont measuring to line measuring. Experimental results based on plain flame
      furnace suggest that L-CARS can acquire about 200 points' temperatures
      effectively in one test, and the length of the measuring line is about 3.6mm. The
      spatial resolution is about 18MUm and the uncertainty is less than 7%, which is
      as the same as the ordinary CARS's.

PMID- 30235504
TI  - [Precise and Rapid Detection of Glutathione by Using Novel Fluorescent Ag
      Nanoclusters].
AB  - Glutathione (GSH) is an important three-peptide molecule, which has the functions
      of antioxidation and detoxification, and plays a crucial role in the fields of
      biology, medicine and food science. It is involved in many important biochemical
      reactions in cells and body fluid, and the changes of GSH content reflect the
      specific health problems of human body. Current methods of GSH detection are
      always complicated, time-consuming and expensive instrument depended, such as
      surface enhanced Raman spectroscopy (SERS), electrochemical analysis, high
      performance liquid chromatography (HPLC) and so on. The probe's photochemical
      properties can be modified by the reaction between GSH and nanoclusters, which
      will result in the changes of fluorescence intensity and wavelength. In this
      paper, a new method to realize precise and rapid GSH detection is developed by
      using silver na-noclusters as a fluorescent probe, and simultaneously measures
      the probe's fluorescence intensity and wavelength. The synthesis of the
      fluorescence probe reported in this paper possesses the advantages of steps
      simple and pollution free, and the GSH detection method has faster response, more
      accurate measurement and smaller relative error over the traditional methods. The
      good specificity of GSH detection among other molecules with the similar
      structure is further proved in control group experiments by comparing the
      differences of their fluorescence intensities and wavelength. The measurement
      accuracy is fully assured due to the insensitivity of the probe to a variety of
      salt ions and amino acids. This technique can be further employed in the
      intracellular detection and imaging of GSH.

PMID- 30235506
TI  - [Calculation of Chlorophyll Fluorescence Characters in Different Light Area to
      Apple Tree Canopy].
AB  - As the basis of plant canopy chlorophyll fluorescence kinetics, light
      distribution within the canopy determines the interaction relationship between
      plant physical processes and ecological environment. Spectroscopy technology
      plays a very important role in building a prediction model of component content
      to plant canopies. However, there is only limited number of reports about
      chlorophyll fluorescence properties of different light intensity areas to free
      spindle apple canopies. In this paper, with the free spindle apple tree as the
      research object, the canopy space of apple tree was divided into five layers, and
      six cube grids with 50cm length of side in each layer, and then the light
      distribution was determined through measuring the light intensity of each cube
      grids space. firstly, spectrum data and characters of chlorophyll fluorescence
      were obtained in the different light area; secondly, a differential spectrum
      curve in red area(680~760 nm) was determined through removing the interference of
      system error by a differential spectrum; thirdly, relationship model has been
      established innovatively between the maximum value in red area(680~760 nm) and
      the chlorophyll fluorescence characters, which has been used as calculation
      method of chlorophyll fluorescence characters in different light area to apple
      tree canopy. Fourthly, root mean square error, mean absolute percentage error,
      mean forecast error were adopted to evaluate the method. The test result shows
      that the accuracy of the method is all above 80%, which can be the theoretical
      basis for pruning and getting best light distribution to apple tree canopy.

PMID- 30235505
TI  - [Soft Measurement of the Purity of the Synthetic Edible Pigment Powder Using
      Fluorescence Spectroscopy Combined with SVM].
AB  - The feature compression algorithm which was reformed from the original Moment
      method was used for the pre-processing of the fluorescence spectral data, then
      combined the data and the Weighted Least Squares Support Vector Machine(WLS-SVM)
      algorithm to establish a robust regression model, which is used for forecasting
      the purity of edible pigment powder. In this paper, brilliant blue and ponceau 4R
      served as an example to discuss the method of forecasting effect of edible
      pigment powder purity. The emission fluorescence spectra of two edible pigment at
      the optimal excitation wavelength were measured by FLS920 fluorescence
      spectrometer. The compression and transformation of the fluorescence spectral
      data was acquired by the feature compression algorithm reformed from the Original
      Moment method. On the one hand the feature compression algorithm shortened the
      operation time, on the other hand it improved the prediction accuracy of the
      model. Then, the concentration prediction model was established after inputting
      the fluorescence spectral data pre-processed into the Weighted Least Squares
      Support Vector Machine. The model gave anastomotic predicted spectral data with
      the actual experiments of the brilliant blue and ponceau 4R, and the average
      coefficient of determination in the half peak width was 0.700 and 0.930
      respectively. There was a good linear relationship between the predicted and the
      nominal concentration of the brilliant blue and ponceau 4R, and the correlation
      coefficients were 0.997 and 0.992 respectively. It can be concluded that, the
      predicted concentration of the brilliant blue and ponceau 4R powder were got the
      results of 61.0% and 72.3% respectively.

PMID- 30235507
TI  - [Fluorescence Spectroscopic Studies on Binding of 20 (S)-Protopanaxatriol with
      Bovine Serum Albumin].
AB  - The interaction between 20(S)-protopanaxatriol (PPT) and bovine serum albumin (
      BSA) was studied with fluorescence quenching technique and ultra-violet
      absorption spectroscopy. The results indicated that PPT led to the intrinsic
      fluorescence quenching of BSA through a static quenching process .The binding
      constants of PPT with BSA obtained with fluorescence quenching method were
      calculated as 0.926 3*10(3) (298 K), 0.618 2*10(3) (308 K), 0.414 4*10(3) L.mol(
      1)(318 K), respectively; while the number binding sites n were close to unity.
      The results showed that the driving force of the interaction between PPT and BSA
      was hydrogen bond and Van der Waals force. The result of synchronous fluorescence
      spectra showed that binding of PPT with BSA could induce conformational changes
      in BSA, that the part of tryptophan became more closely. According toFoster
      fluorescence resonance energy transfer theory, the binding distance r and energy
      transfer efficiency E were respectively 26.2 nm and 0.32.

PMID- 30235508
TI  - [Study on Recognition Model of Phyllosilicate of Martian Surface].
AB  - Phyllosilicate belongs to hydrated silica, which is a principal form of hydrous
      minerals on the martian surface. It's also an indicator in comparing different
      sediments and degree of aqueous alteration. Therefore, it's essential to
      establish its recognition model for studying the geologic evolution of the Mars.
      Short-wave infrared (SWIR) spectral bands and thermal infrared (TIR) spectral
      bands have distinct spectral response to the mineral groups and ions, so they
      have distinctive advantages in detecting minerals. However the method of
      combining SWIR and TIR to recognize phyllosilicate is rarely studied. Based on
      the USGS spectral library, facing Compact Reconnaissance Imaging Spectrometer for
      Mars(CRISM) and Thermal Emission Imaging System(THEMIS),we conducted the research
      on the mechanism of the spectral response of phyllosilicate, and established the
      SWIR and TIR identification model respectively, then combined the SWIR and TIR
      spectral features to build the combined recognition model of phyllosilicate with
      Fisher discriminant analysis. The results of cross validation show that the
      identification accuracy of combined model is the highest, which can correctly
      classify 90.6% of the mineral samples and improve the identification precision of
      phyllosilicate effectively.

PMID- 30235509
TI  - [Simultaneous Detection of Multiple Quality Parameters of Pork Based on Fused
      Dual Band Spectral].
AB  - For dual band visible/near infrared spectroscopy system (350~1 100 and 1 000~2
      500 nm), there exsits a band overlap and for the same sample the reflectivity
      data were unlike due to the performance difference between instruments. A band
      connection and data fusion method was proposed in this paper to make better use
      of the dual-band data. A dual-band visible/near-infrared spectroscopy system was
      built in the study to collect 60 pork samples' reflectance spectra. The
      reflectance spectra of samples were performed with pretreatment methods of
      Savitzky-Golay (S-G) and standard normal variable transform to eliminate the
      spectral noise. Then partial least squares regression (PLSR) prediction models of
      pork quality attributes (color, pH and cooking loss) based on single-band
      spectrum and dual-band spectrum were established, respectively. For the cross of
      two band overlap, the data were connected and integrated using the method put
      forward in this paper and then PLSR models were established based on the
      integrated data. The PLSR model yielded prediction result with correlation
      coefficient of validation (R(p)) of 0.948 8, 0.920 0, 0.950 5, 0.930 1 and 0.903
      5 for L(*), a(*), b(*), pH value and cooking loss, respectively. To simplify the
      model, uninformative variables elimination (UVE) was employed to select
      characteristic variables. The experimental results show that the proposed method
      was able to achieve a better fusion of the two band spectral data, and it was
      good for the establishment of a more simplified and better prediction model.

PMID- 30235510
TI  - [Measuring the Spectrum of Extinction Coefficient and Reflectance for Cadmium
      Compounds from 400 to 900 nm].
AB  - The key to extract the contents of cadmium in water by using remote sensing
      technique is to measure the spectrum of extinction coefficient per g.L(-1) and
      reflectance for its compounds. So in this paper, firstly, we choose two kinds of
      cadmium compounds, cadmium sulfide (CdS) and cadmium oxide (CdO), which are most
      commonly exsit in natural water, to measure the spectrums of extinction
      coefficient and reflectance for them. We use the equipment, designed on our own,
      which can adjust the path length of light passing and make our measuring results
      more accurate at visible and near-infrared wavelength range than others. Then we
      use Analytical Spectral Devices (ASD) spectrometer to measure the radiance of the
      light spot, which is from the direct light passed through cadmium compounds
      solutions of different concentrations reflected by the standard board. Using the
      ratio method to eliminate environmental errors and the effects of the thimbleful
      of suspended solids in water, we obtain the extinction coefficient per g.L(-1) of
      these two kinds of cadmium compounds from 400 to 900 nm. Secondly, we use ASD
      spectrometer to measure the reflectance spectrum of them in the sunny day at
      outdoor. The reflectance we obtain in this paper can help us to calculate the
      absorption and scattering coefficient per g.L(-1) in the future. The measuring
      results show that the extinction coefficient spectrum of CdS has two troughs at
      550 and 830 nm and one peak at 675 nm. And the extinction coefficient spectrum of
      CdO decrease from purple to near-infrared. Both of their coefficient spectrums in
      blue are larger than green and red. And the value of the extinction coefficient
      per g.L(-1) of CdS is larger than CdO in the whole measuring wavelength range.
      The reflectance of CdS in yellow and red is larger than purple and blue, which
      increases rapidly from 500 to 650 nm and then leveling off. While the reflectance
      of CdO increase linearly from 525 to 900 nm. Both have obvious spectral
      characteristic. According to our results, the largest extinction coefficient
      appear at blue color, while the largest reflectance appear at yellow and red,
      which means that those bands are the most sensitive wavelength to detect the
      change of cadmium concentration in water. This study carries out with optical
      parameters measurements for optical activity of cadmium compounds specifically
      for water quality remote sensing for the first time. We conclude that the
      extinction coefficient and reflectance spectrums we obtained are reasonable, and
      the results can be used as the base parameter in the remote sensing inversion
      model for cadmium contents in water, which provides a breakthrough on using
      remote sensing technique to extract the heavy metal contents in water. Obtained
      these two optical parameters in this paper can provide powerful reference for
      band selection of the remote sensing image, which is used to extract cadmium
      contents in water, as well as provide the necessary important parameters of the
      remote sensing inversion model of cadmium contents in water.

PMID- 30235511
TI  - [Preparation of Zinc Dibenzyl Dithiocarbamate and Its Spectral Analysis].
AB  - In the study, zinc methyl mercaptobenzimidazole (MMBZ) was synthesized by one
      step method. MMBZ was detecued and characterized by FTIR, UV-Vis, XRD, TG-DSC.
      Its micro-structure and intrinsic regularity were revealed. Chemical bond types
      into MMBZ molecule were revealed by FTIR. The final product was determined MMBZ.
      There absorption peaks were detected by UV-Vis at 219.6,245.5,302.2 nm
      respectively, due to n->sigma(*),pi->pi(*),pi->pi(*) electronic transitions, led
      by S-C, benzene and five element heterocyclic in MMBZ molecule. It could provide
      experimental basis with enterprise to test MMBZ product quality and speculate its
      structure. It was shown that MMB was a ligand of MMBZ, and its basic structure of
      MMB was retained still by XRD spectra. The structure of MMBZ molecule was
      amorphous. Two kinds of information were detected with TG-DSC as quality change
      and thermal effect. There were five absorption peaks of 67.5, 155.3, 253.7,
      324.8, 391.3 C, due to impurity solvent decomposition peak, phase transition peak
      and decomposition of MMBZ respectively. The scheme of one step preparation of
      composite environment-friendly rubber antioxidant MMBZ was feasible. The
      structure of MMBZ could be speculated by results of its detecting. It could
      provide the basis of experimental data on association MMBZ performance, exploring
      its anti-aging mechanism and extending the scope of MMBZ application.

PMID- 30235513
TI  - Editor-in-Chief's Commentary: Integrating Economics Into Innovation.

PMID- 30235514
TI  - DIA 2013 49th Annual Meeting Student Poster Abstracts.

PMID- 30235512
TI  - p40 Immunohistochemistry Is an Excellent Marker in Primary Lung Squamous Cell
      Carcinoma.
AB  - BACKGROUND: Lung cancer is the third most common cancer worldwide. With major
      advances in the molecular testing of lung cancers and the introduction of
      targeted therapies, the distinction between adenocarcinoma and squamous cell
      carcinoma as well as pathologic subtyping has become important. Recent studies
      showed that p40 is highly specific for squamous and basal cells and is superior
      to p63 for diagnosing lung squamous cell carcinoma. The aim of this study was to
      evaluate the use of p40 immunohistochemical stain in the diagnosis of non-small
      cell lung carcinoma and its potential to replace current p63 antibody as the best
      immunohistochemical squamous marker. METHODS: Seventy formalin-fixed paraffin
      embedded cases previously diagnosed as primary lung squamous cell carcinoma (n =
      35) and lung adenocarcinoma (n = 35) from January 2008 to December 2016 were
      retrieved. The results of tumour cell immunoreactivity for p40 and p63 antibodies
      in lung squamous cell carcinoma and lung adenocarcinoma were compared. RESULTS:
      p40 was expressed in 27 cases of lung squamous cell carcinoma (77.1%). All cases
      of lung adenocarcinoma (35/35, 100%) were negative for p40. p63 expression was
      positive in 30 cases of lung squamous cell carcinoma (85.7%) and 13 cases of lung
      adenocarcinoma (37.1%). Reactivity for both p40 and p63 in lung squamous cell
      carcinoma was strong and diffuse, whereas variable reactivity was observed in
      lung adenocarcinoma. CONCLUSIONS: p40 is an excellent marker for distinguishing
      lung squamous cell carcinoma from adenocarcinoma, and p40 expression is
      equivalent to p63 expression in lung squamous cell carcinoma.

PMID- 30235515
TI  - Pharmacotherapeutic Follow-up and Pharmacogenetics of CYP2C9 and CYP3A4 in
      Antihypertensive Therapy: A Pilot Study in a Community Pharmacy.
AB  - No pharmacogenetic studies have yet been conducted in community pharmacies,
      despite pharmacogenetics being an emerging discipline. Pharmacotherapeutic follow
      up (PFU) was performed for 6 months in 37 patients receiving antihypertensive
      treatment, and they were genotyped for variant alleles *2 and *3 in the CYP2C9
      gene and *1B in CYP3A4. Systolic blood pressure, cardiovascular risk, and
      adherence improved with PFU. Most of the interactions between drugs were
      represented by concurrent administration of statins and calcium channel blockers,
      which both use CYP3A4 for their metabolism. Heterozygotic patients for the
      CYP2C9*2 allele showed higher mean heart rate values after PFU than homozygous
      patients (73.4 +/- 10.0 pulse/min vs 66.2 +/- 10.6 pulse/min, respectively; P =
      .048). Carriers of CYP2C9*2 showed a tendency to less frequent negative outcomes
      associated with medication due to inefficacy than homozygous patients (50% vs
      78.9%, respectively; P = .072). Pharmacogenetics and PFU can be used in community
      pharmacies to carry out a more exhaustive study of medication in hypertensive
      outpatients.

PMID- 30235516
TI  - The Regulation of Companion Diagnostics: A Global Perspective.
AB  - The emerging trend of validated biomarkers, otherwise known as companion
      diagnostics (CDx), is playing a key role in helping pharmaceutical companies
      acquire rapid regulatory approval of their targeted therapeutics while saving on
      development time and costs. In today's challenging regulatory arena, diagnostics
      led treatment can improve the reimbursement and market access for drugs. All of
      this has prompted research in the use of such biomarkers with targeted
      therapeutics for predicting response to therapy, hence beginning the revolution
      of personalized medicine. With the current target area being oncology, other
      therapeutic areas are also now being explored. As an increasing number of
      pharmaceutical firms are penetrating the CDx arena and looking to partner with
      diagnostics developers, this does not come without its challenges. The
      codevelopment process is complex, and many hurdles may need to be crossed before
      a perfect model can be achieved. To add further to the complexity, the global
      regulatory landscape for CDx is in a state of flux, making it extremely
      challenging for industry to keep up with the increasing demands of the
      regulators. This article provides an overview of the changing regulatory
      landscape for CDx in some of these key markets and an insight to deal with the
      challenges associated with developing a successful global regulatory strategy for
      a CDx product. The views presented in this article are mainly from a diagnostics
      perspective.

PMID- 30235517
TI  - Analysis Sets and Inference in Clinical Trials.
AB  - The debate about what constitutes a valid analysis of clinical trial data is
      longstanding. While the intention-to-treat (ITT) principle seems to be widely
      accepted in the context of controlled clinical trials aiming to show superiority
      of an experimental treatment over a control, the best choice for a noninferiority
      trial is still under discussion. In this article, it is argued that the
      definition of analysis sets and the purpose of ITT and per-protocol analyses
      proposed in the International Conference on Harmonisation biostatistics guideline
      E9 should be revised to allow for more appropriate analyses, given that
      statistical methodology has been developed since the guideline was issued.

PMID- 30235518
TI  - Understanding the Diagnosis and Treatment of COPD and Asthma to Better Inform
      Site Selection and Patient Recruitment Planning.
AB  - There is an increasing worldwide population of people with chronic obstructive
      pulmonary disease (COPD) and asthma. Mortality from COPD is expected to double
      over the next 3 decades, making it the third leading cause of death worldwide. It
      is estimated that as many as 300 million people of all ages and all ethnic
      backgrounds worldwide suffer from asthma. Devising and implementing a successful
      strategy for the execution of COPD and asthma trials requires a multifaceted
      approach, coupled with an understanding of the factors that drive patient
      recruitment. However, little has been written about recruitment and the
      comparative success of different recruitment strategies. This paper focuses on
      results obtained from various assessments of treatment guidelines compliance,
      patient diagnosis and treatment, approved therapies, and patient profiles that
      have helped provide insight into critical factors to help drive country, site,
      and patient recruitment strategies.

PMID- 30235519
TI  - Improving Good Practice: A Survey of Unlicensed and Off-Label Drug Use in a
      General Hospital in China.
AB  - BACKGROUND: Off-label and unlicensed drug use is common in Europe and the US;
      however, information about this issue in China is limited. OBJECTIVE: To
      determine the scope and scale of off-label and unlicensed drug use in general
      hospitals in Shanghai, China, and to evaluate the varying levels of supporting
      evidence. METHODS: A total of 493 cases of discharge history were randomly
      sampled. Off-label uses were defined according to package inserts, the China
      Pharmacopeia Clinical Medication Notice (2010), and New Pharmacology (16th
      edition). All drugs administered were assessed to determine whether their use was
      unlicensed and off-label. RESULTS: There were 459 cases (93.10%) of off-label
      drug use, and 47.64% of total therapeutic drugs prescribed were off-label. Of
      these cases, 8.72% of patients received 1 off-label drug, and 9.94% of patients
      received 2 off-label drugs. Use of multiple off-label medications per patient was
      also common, and the percentage of patients receiving 3, 4, 5, 6, 7, 8, 9, and
      >=10 medications was 9.74%, 9.74%, 8.72%, 7.91%, 12.58%, 7.10%, 5.88%, and
      12.78%, respectively. Categories of off-label drugs used most frequently were
      vitamins, cardiovascular drugs, and gastroenteric drugs. The most common off
      label use was that the indication for which a drug was prescribed was not
      approved (83.49%); other off-label uses involved disregard for contraindications
      and drug incompatibility (6.37%), dose exceeding approved amount (4.76%),
      unapproved route of administration (4.65%), and unapproved dosing intervals
      (0.73%). Vitamins and nutritional supplements are the drugs most frequently
      prescribed off-label, while off-label use of vasodilators, lipid-lowering drugs,
      and adjuvant therapy medications for cardiovascular and cerebrovascular
      conditions is also common. CONCLUSION: Unlicensed and off-label prescribing of
      drugs may be common in China.

PMID- 30235520
TI  - A Framework for Managing the Minimal Clinically Important Difference in Clinical
      Trials.
AB  - There is a long history of discussions about what is a minimal clinically
      important difference (MCID) and how this term applies to clinical research. This
      paper deals with a practical framework for MCID and its applicability to clinical
      trials. A literature review on the topic confirmed the fundamental role of MCID
      for the clinical research, although no guide on how to best use the MCID in
      clinical trials was identified. We propose a framework that takes into account
      (1) the definition of MCID as a term when random variable is discussed, (2) a 4
      level approach for classifying the MCID evidence to be considered in a clinical
      development program, and (3) a method of MCID evaluation, defined in a
      scientifically sound protocol. The proposed framework can prompt and steer
      stakeholders to improve the methodological sense of clinical trials based on the
      definition of MCID at the level of efficacy or safety, increase the quality of
      data derived from clinical trials and reporting of results, and allow effective
      planning of drug development programs.

PMID- 30235521
TI  - Views on Emerging Issues Pertaining to Data Monitoring Committees for Adaptive
      Trials.
AB  - In this paper, the authors express their views on a range of topics related to
      data monitoring committees (DMCs) for adaptive trials that have emerged recently.
      The topics pertain to DMC roles and responsibilities, membership, training, and
      communication. DMCs have been monitoring trials using the group sequential design
      (GSD) for over 30 years. While decisions may be more complicated with novel
      adaptive designs, the fundamental roles and responsibilities of a DMC will remain
      the same, namely, to protect patient safety and ensure the scientific integrity
      of the trial. It will be the DMC's responsibility to recommend changes to the
      trial within the scope of a prespecified adaptation plan or decision criteria and
      not to otherwise recommend changes to the study design except for serious safety
      related concerns. Nevertheless, compared with traditional data monitoring, some
      additional considerations are necessary when convening DMCs for novel adaptive
      designs. They include the need to identify DMC members who are familiar with
      adaptive design and to consider possible sponsor involvement in unique
      situations. The need for additional expertise in DMC members has prompted some
      researchers to propose alternative DMC models or alternative governance model.
      These various options and authors' views on them are expressed in this article.

PMID- 30235522
TI  - Search Strategies Used for Meta-Analyses Published on Cardiovascular Drug
      Therapy.
AB  - PURPOSE: Meta-analyses are routinely shaping patient care decisions. However, it
      is unknown whether meta-analyses are increasing in cardiology or whether complete
      search strategies are used. The purpose of this study was to assess the quality
      of search strategies of meta-analyses. METHODS: Meta-analyses assessing
      cardiovascular drug therapy published from 2006 to 2011 were identified through
      PubMed/Medline with the terms "cardiovascular agents" and "drug therapy."
      RESULTS: A total of 130 meta-analyses were identified. There was a 100% increase
      with the largest growth from 2008 to 2009. Only half of the analyses used 3
      databases to identify studies for inclusion, which was predictive of using search
      terms ( P < .01; odds ratio, 3.05, 95% confidence interval, 1.341-6.952) and
      using a quality assessment tool ( P < .001; odds ratio, 3.05; 95% confidence
      interval, 2.038-8.066). CONCLUSIONS: Meta-analyses evaluating cardiovascular drug
      therapy increased in 2011. Meta-analyses should exhaust all resources to identify
      trials for inclusion. As meta-analyses continue to change clinical practice,
      researchers and clinicians must critically assess the quality of these studies.

PMID- 30235523
TI  - Supplement Use Among Pregnant Women in Ethiopia: Prevalence and Predictors.
AB  - Purpose The purpose of this article was to assess the pattern of supplement use
      and associated factors among pregnant women in Ethiopia. Methods A facility-based
      cross-sectional study was conducted. A total of 339 pregnant women were included
      in the study, 63 (18.3%) and 23 (6.8%) of whom used at least 1 supplement during
      pregnancy and 2 to 4 weeks prior to pregnancy, respectively. Only 3 women were
      prescribed folic acid during pregnancy. The pregnant women were interviewed to
      collect supplements use and pregnancy-related information through a pretested
      semistructured questionnaire. Subsequent charts of prescribed supplements were
      reviewed using a pretested data collection format. Results The majority (76.4%)
      of the women claimed no awareness about the benefits of early supplementation.
      Supplement use was about 8 times higher among women with > 3 children (adjusted
      odds ratio, 7.85; 95% confidence interval, 1.69-36.28; P = .008) than among
      nulliparous women, and about 6 times higher among women in their second trimester
      (adjusted odds ratio, 6.26; 95% confidence interval, 1.91-20.55; P = .03) of
      pregnancy compared to those women in their first trimester. Conclusion Overall
      supplement use, particularly folic acid intake, was found to be negligible during
      the prenatal as well as antenatal periods. The majority of the women in the study
      lacked awareness about the benefits of supplementation and potential risks
      associated with the absence of folic acid during pregnancy. Information by the
      media and health care personnel given to childbearing women about the need to
      take folic acid to prevent neural tube defects seems to improve the intake of
      folic acid during the protective period.

PMID- 30235524
TI  - Investigation of Characteristics of Japanese Clinical Trials in Terms of Data
      Variability.
AB  - BACKGROUND: Because Asian countries have become involved in multiregional
      clinical trials, it is increasingly important to understand the characteristics
      of each country in terms of clinical trials to seek an appropriate strategy for
      worldwide drug development. Since variability of data is one of the important
      factors in clinical trials, variability of Japanese data, such as shown in
      coefficient of variation (CV) and standard deviation (SD) values, is an area of
      interest from which to consider an appropriate development strategy. METHODS: To
      characterize variability of Japanese data compared with non-Japanese data, the
      authors selected pharmaceutical products recently approved in Japan, reviewed
      their clinical trial data, and analyzed these data for efficacy response
      variables in Japan and Western countries. Twenty-nine products were selected for
      the examination. RESULTS: Japanese data are similar to non-Japanese data in terms
      of data variability, and the ratios of the Japanese to the non-Japanese values
      for CV and SD were within a relatively narrow range for most products.
      CONCLUSIONS: Japanese clinical trial data showed variability similar to that of
      non-Japanese data for most cases. It is expected that further studies to
      characterize specific regions in terms of clinical trial data will be conducted
      to consider an appropriate strategy for worldwide drug development.

PMID- 30235525
TI  - Comparison of Stakeholder Metrics for Traditional and Adaptive Development and
      Licensing Approaches to Drug Development.
AB  - This study evaluates whether an adaptive development and licensing approach to
      drug development, compared with approaches widely used today, might have tangible
      advantages across stakeholder groups, thereby facilitating the future adoption.
      Details involving actual and modeled clinical development and licensing programs
      for 3 case studies were used as inputs into a discounted cash flow spreadsheet
      model. Outputs included net present value and expected net present value, which
      are metrics considered as key incentives for pharmaceutical developers, and
      change in patient access over the product life and numbers of appropriately and
      inappropriately treated patients, which are metrics considered as key incentives
      for regulators, patients, and prescribers. Actual and modeled development
      programs were compared using an "adaptiveness" scoring algorithm. Generally, the
      more adaptive programs correlated with more favorable stakeholder outcomes.
      However, favorable outcomes may be overwhelmed in some cases, and the causative
      conditions and stakeholder reactions need to be defined.

PMID- 30235526
TI  - Good Laboratory Practice Inspections in Japan Between Fiscal Years 2009-2011.
AB  - This study presents findings from Good Laboratory Practice (GLP) inspections in
      Japan. In Japan, GLP inspections of facilities that test pharmaceuticals and
      medical devices are coordinated by the Office of the Conformity Audit of the
      Pharmaceuticals and Medical Devices Agency (PMDA). All of the applications
      received for GLP inspection by the PMDA from fiscal years (FY) 2009 to 2011 were
      reviewed. The article analyzes the VAI (Voluntary Action Indicated)
      recommendations that were made to the test facilities after inspection. Using
      these data sources, the study calculates the number of VAI recommendations made
      to the facilities, classifies the topics of notification, and demonstrates trends
      in the VAIs issued in FY2011. In FY2011, the number of VAI issues about animal
      care and management as well as computerized systems increased compared with
      FY2009 and FY2010.

PMID- 30235527
TI  - Blinded Sample Size Recalculation in Longitudinal Clinical Trials Using
      Generalized Estimating Equations.
AB  - In clinical trials in which outcomes are measured repeatedly during the follow-up
      phase, data analysis is frequently performed using generalized estimating
      equations (GEEs). Sample size calculation is then especially challenging since in
      addition to the treatment effect, the intrasubject correlation and the
      variability of the model error term have to be specified. In this article, the
      authors investigated by Monte Carlo simulations whether a blinded midcourse
      estimation of these quantities in an internal pilot study design is feasible in
      such trials and whether nominal type I and type II error rates are preserved when
      the estimates are used for sample size recalculation. The actual type I error
      rates of the blinded sample size recalculation procedure turned out to agree well
      with the nominal levels. Furthermore, the simulated power was observed to be near
      the target value as long as the sample size of the internal pilot study was
      sufficiently high and the bound effects induced by the range of the correlation
      were limited. The proposed procedure is a helpful tool to achieve robustness of
      the power with respect to initial misspecifications in the planning stage in
      clinical trials analyzed by GEE.

PMID- 30235529
TI  - Editor-in-Chief 's Commentary: DIA, TIRS, and ICH.

PMID- 30235528
TI  - Sample Size and Data Monitoring for Clinical Trials With Extremely Low Incidence
      Rates.
AB  - In clinical trials, statistical analyses on incidence rates detect significant
      differences between the responses from groups. Sample size estimation is always
      one of the key aspects in clinical trials that have limited budgets. A prestudy
      power analysis for sample size calculation is often performed to select an
      appropriate sample size that will achieve a desired power (ie, the probability of
      correctly detecting the significant difference if such a difference truly exists)
      at a prespecified level of significance. In practice, it is expected that a
      greater sample size is needed to detect a smaller difference. A much larger
      sample size is required to detect a relatively small difference, especially for
      those clinical studies with extremely low incidence rates. Thus, sample size
      calculation based on prestudy power analysis may not be feasible in practice. In
      this case, as an alternative, the authors propose to justify a selected sample
      size based on a precision analysis and a sensitivity analysis. A recommended step
      by-step procedure for sample size determination in clinical trials with extremely
      low incidence rate is given. A statistical procedure for data safety monitoring
      based on the probability statement during the conduct of the clinical trial is
      also proposed.

PMID- 30235530
TI  - Labeling Standards for Biosimilar Products.
AB  - In 2010 Congress established a regulatory pathway for the approval of biosimilar
      products in the United States. FDA has embarked on developing the implementation
      framework for this pathway which includes creating guidance to assist biosimilar
      manufacturers in the development of these products. However, to date, the
      guidances have focused primarily on the technical standards that manufacturers
      should consider in order to successfully achieve product registration. As
      labeling is critical to the safe and effective use of medicinal products, as well
      as being essential to the content of subsequent promotional material, FDA should
      consider providing labeling standards that ensure that health care providers have
      the information needed to make informed decisions regarding the use of these
      important products.

PMID- 30235531
TI  - Comparison of Drug Approvals in Europe Versus the United States: An Analysis of
      Discrepancies Between Drug Products Reviewed by EMA and FDA.
AB  - BACKGROUND: Regulators from the US Food and Drug Administration (FDA) and the
      European Medicines Agency (EMA) do not always agree on interpretation of data for
      a drug's safety and efficacy. METHODS AND RESULTS: The authors compared all new
      molecular entities approved or rejected in a 5-year period from 2007 to 2011,
      identified where FDA and EMA reviews resulted in different regulatory decisions,
      and explored potential mechanisms for the discrepancies. Thirteen entities were
      associated with different regulatory decisions, and 2 drugs were withdrawn from
      their respective markets in 2010: one from the US (Mylotarg; gemtuzumab
      ozogamicin) and the other in Europe (Thelin; sitaxentan sodium). CONCLUSIONS:
      There are relatively few cases where FDA and EMA substantively differ with regard
      to product approvals and market withdrawals. It is likely that the scientific and
      cultural differences between FDA and EMA will continue to diminish over time,
      because these two agencies increasingly work together as pharmaceutical product
      development increasingly becomes a global endeavor.

PMID- 30235532
TI  - Important Safety Information or Important Risk Information? A Question of Framing
      in Prescription Drug Advertisements.
AB  - The summary of risks in a prescription drug print advertisement is typically
      headlined either "Important Safety Information" or "Important Risk Information."
      Research has shown that words used to frame information can influence
      interpretation of the information. We examined the impact of headline framing on
      risk perception among consumers viewing prescription drug ads. Participants (N =
      2000) were randomly assigned to see the title "Important Safety Information" or
      "Important Risk Information" before reading a description of risks for a
      fictitious drug. Participants then answered questions about the perceived risk of
      the drug, attempted to recall the section heading, and reported demographic
      characteristics. Results revealed no differences between participants in the 2
      conditions, suggesting that framing drug risk information in terms of its safety
      or risk does not differentially affect consumer risk perception.

PMID- 30235533
TI  - Transaction Cost Analysis of the New Drug Application Process: A Case Study of a
      Multinational Pharmaceutical Company in Japan.
AB  - The aim of this study was to measure the transaction costs of a new drug
      application (NDA) process in Japan in a case study of a multinational
      pharmaceutical company. The NDA process was viewed as involving transactions
      among 3 organizations: the headquarters, the Japanese subsidiary, and the
      Pharmaceuticals and Medical Devices Agency. Transaction costs were calculated by
      multiplying the time for each transaction by an hourly wage. Work time for the
      NDA process totaled 14,710.6 hours and was estimated to cost US$558,000 in human
      resource-related expenditure in the company. The total time for intracompany
      transactions was 7662.5 hours (52.1% of all transactions), which was similar to
      that of transactions with the Pharmaceuticals and Medical Devices Agency (7048.1
      hours, 47.9%). Also found was a press-and-slack procedure in time course
      observation. In conclusion, the current NDA system in Japan imposes a
      considerable time and cost burden behind that of the visible official process on
      a multinational company.

PMID- 30235534
TI  - The Quality of Reporting Harms-Related Data in Clinical Trials of Adjuvant
      Trastuzumab in Early-Stage Breast Cancer Treatment.
AB  - Randomized controlled trials (RCTs) usually place less emphasis on the harmful
      effects than on the efficacy of interventions. The 10 CONSORT (Consolidated
      Standards of Reporting Trials) recommendations for harms reporting aim to improve
      harms data reporting of RCTs. The aim of this study was to assess the reporting
      of harms data in adjuvant trastuzumab studies in early-stage breast cancer. The
      resources PubMed, Cochrane Library, the American Society of Clinical Oncology,
      and the San Antonio Breast Cancer Symposium were searched for relevant RCTs that
      met the eligibility criteria. Each RCT was reviewed to determine whether the
      reporting of data complied with the 10 CONSORT recommendations for harms
      reporting, and the frequency of compliance with each CONSORT recommendation
      criterion was reviewed. Five RCTs met the eligibility criteria. Overall, selected
      RCTs failed to adhere to CONSORT recommendations in all sections of reporting.
      These results suggest that there is a need to standardize harms data reporting.

PMID- 30235535
TI  - Utilization of Recently Established Drug Information Centers Located in the
      Public Hospitals of Addis Ababa, Ethiopia: An Assessment.
AB  - A drug information center is a unit designed for receiving, collecting,
      analyzing, and providing unbiased, accurate, and up-to-date information about
      drugs and their use. The drug information centers located in 4 public hospitals
      of Addis Ababa, Ethiopia, were assessed in this study. They received a total of
      467 drug information queries during their functional period until the time of
      this study. Among these queries, only 409 were eligible to be included in the
      analysis. The majority of the queries were from public hospitals (69%), mostly
      from health care professionals (94.9%), out of which physicians were the highest
      (49.7%), followed by pharmacists (32.8%). The study found that the most
      frequently encountered requests were related to therapeutic use (17.3%), followed
      by general product information and product availability; the highest number of
      queries concerned the use of anti-infectives (29%).

PMID- 30235537
TI  - A Novel Design for Decision Rules Based on Statistical Testing Strategies of
      Binary Endpoints in a Definitive Go/No-Go Single-Treatment Clinical Study.
AB  - In drug development, a definitive go/no-go clinical study is sometimes conducted
      before major investment is made to advance the development into the next stage.
      Such a study sometimes focuses on a key binary endpoint, such as a particular
      adverse event, treatment failure, or device problem. However, such a study is
      often constrained by budget and scope, which limit the sponsor's ability to draw
      clear conclusions. This paper proposes a novel design that uses Wilson confidence
      intervals to devise statistical testing strategies that allow the decision makers
      to arrive at certain definite conclusions within the constraint of the study's
      scope.

PMID- 30235536
TI  - Investigation of the Safety Profiles of Japanese Clinical Trials.
AB  - BACKGROUND: The increasing attrition rates of new drug research and development
      have become a global problem. To tackle this problem as well as the problem of
      "drug lag" in Japan, strategies utilizing multiregional clinical trials (MRCTs)
      are now being commonly applied. It is important to determine whether clinical
      data in a specific country and region have tendencies or patterns that will help
      us to consider an appropriate strategy for drug development in the specific
      region as well as worldwide. However, little has been studied on strategies and
      methods for drug development to pursue simultaneous development taking into
      account these characteristics. It would be valuable to determine and characterize
      the safety profile of Japanese clinical trial data. METHODS: To characterize the
      overall safety profile of Japanese data in terms of the frequency of adverse
      events (AEs), serious AEs, and discontinuation due to AEs compared with non
      Japanese data, 73 pharmaceutical products recently approved in Japan were
      selected. Their clinical trial safety data, derived from comparable studies
      conducted in Japan and Western countries using the bridging strategy and MRCTs,
      were reviewed and analyzed. RESULTS: Japanese data are similar to non-Japanese
      data in terms of overall frequency of AEs; however, the sample size of Japanese
      patients in the bridging studies and MRCTs was generally smaller than that in non
      Japanese data. CONCLUSIONS: The safety profile in Japanese clinical data was
      shown to be similar to that of non-Japanese data from the standpoint of overall
      frequency of AEs. This finding should be encouraging to pharmaceutical companies
      and the health authority in Japan to accelerate participation in MRCTs.

PMID- 30235539
TI  - ICH: Strengths, Weaknesses, and Future Tasks.
AB  - The International Conference on Harmonisation of Technical Requirements for
      Registration of Pharmaceuticals for Human Use (ICH) started in 1990 with the
      mission to harmonize technical guidelines and obligations for the development and
      authorization of human pharmaceuticals through the cooperation of drug regulatory
      authorities and the pharmaceutical industry of the main drug markets in the
      world. To evaluate the achievements of ICH over the last 23 years, 30 European
      experts were interviewed. The interviewee panel was selected to encompass
      representatives of both the pharmaceutical industry (20 interview partners) and
      the health authorities (10 interview partners). Many of the interview partners
      have actively contributed to ICH by leading or participating in working groups.
      Based on the interviews, this article highlights the strengths and weaknesses of
      ICH with a focus on ideas and visions to improve the status quo.

PMID- 30235538
TI  - Understanding the Role and Evidence Expectations of Health Technology Assessment
      and Coverage/Payer Bodies: What Are They Looking for, and How and Why Does This
      Differ From What Regulators Require?
AB  - Pharmaceutical companies have a good understanding of the needs and requirements
      of regulatory bodies, but the evidence expectations of health technology
      assessment (HTA) and coverage/payer bodies are less well understood and
      addressed. This paper seeks to improve this understanding by providing an
      overview of the expectations of HTA and coverage/payer bodies, explaining how and
      why these differ from those of regulators, and describing the extent and
      limitations of work on harmonization. The article goes on to describe ways in
      which HTA and coverage/payer bodies' expectations can be addressed, and to
      encourage industry to interact with HTA and coverage/payer bodies to increase
      mutual understanding and hence promote more efficient development of and access
      to innovative medicines.

PMID- 30235540
TI  - Assessing the Quality of Database Search Strategies Utilized by Meta-analyses
      That Evaluate Infectious Disease Drug Therapy.
AB  - Meta-analyses are increasingly influencing clinical practice, but significant
      methodological flaws have been reported. The purpose of this study was to
      evaluate the quality of search strategies utilized by anti-infective meta
      analyses. The Embase database was searched for meta-analyses evaluating anti
      infective drug therapy; 103 of 268 identified citations met inclusion criteria
      and were evaluated. A total of 80.6% of meta-analyses used search terms, and an
      average of 4.3 databases (Medline, 98.1%; Cochrane, 93.2%; Embase, 76.7%) were
      searched to identify relevant articles for inclusion. The majority of meta
      analyses used a quality assessment tool (84.5%) and reported positive results
      (59.2%). The average impact factor of journals publishing meta-analyses was 5.7
      +/- 3.4. The number of resources searched was associated with the impact factor (
      P = .0013). The majority of anti-infective meta-analyses used rigorous search
      strategies to identify all relevant studies for evaluation. This finding is
      inconsistent with reports in other therapeutic areas that have questioned the
      quality of meta-analyses, and it may increase confidence in anti-infective meta
      analyses.

PMID- 30235542
TI  - Quality Standards and Current Status of Ophthalmic Formulations in Indian
      Pharmacopoeia and National Formulary of India.
AB  - The global ophthalmic formulations (OFs) market is expanding dramatically with
      the approval of new drug formulations for a variety of ophthalmic indications by
      competent authorities in various countries. In India, the Central Drug Standards
      Control Organization (CDSCO) and Indian Pharmacopoeia Commission (IPC) are making
      efforts for approval and setting the standards for OFs, respectively. In
      fulfillment of the requirements of the Drugs and Cosmetics Act of 1940, the IPC
      is publishing an official book of standards for drugs known as the Indian
      Pharmacopoeia (IP). There are 44 ophthalmic active pharmaceutical ingredients
      (APIs) and combinations approved by CDSCO as of 2011; the IP 6th edition (2010)
      prescribes the quality standards monographs for 41 ophthalmic APIs and
      formulations. The IP monograph of OFs also includes description, identification,
      impurities, assay, and specific tests. In addition, the IPC is publishing the
      National Formulary of India (NFI), which covers 23 OFs for the diagnosis and
      treatment of various eye diseases. Both the IP and NFI play a significant role in
      monitoring and improving the safety and efficacy of medicines, with specific
      emphasis on OFs.

PMID- 30235541
TI  - A Practical Guide to Data Monitoring Committees in Adaptive Trials.
AB  - Adaptive clinical trials require access to interim data to carry out trial
      modification as allowed by a prespecified adaptation plan. A data monitoring
      committee (DMC) is a group of experts that is charged with monitoring accruing
      trial data to ensure the safety of trial participants and that in adaptive trials
      may also play a role in implementing a preplanned adaptation. In this paper, we
      summarize current practices and viewpoints and provide guidance on evolving
      issues related to the use of DMCs in adaptive trials. We describe the common
      types of adaptive designs and point out some DMC-related issues that are unique
      to this class of designs. We include 3 examples of DMCs in late-stage adaptive
      trials that have been implemented in practice. We advocate training opportunities
      for researchers who may be interested in serving on a DMC for an adaptive trial
      since qualified DMC members are fundamental to the successful execution of DMC
      responsibilities.

PMID- 30235543
TI  - The Role of Universities in the Commercialization of Medical Products: A Survey
      of Industry Views.
AB  - Survey methods were used to explore the expectations and recommendations of
      senior business development professionals with respect to the roles, activities,
      and interactions with US universities in the development of new medical products.
      This target group was chosen because it was judged to be most likely to interact
      with university faculty and technology transfer services and seek and acquire
      university assets. The survey instrument was first reviewed by a focus group of
      individuals with experience both in technology transfer and in academic or
      industry policy, then distributed to a selected subset of 80 business development
      professionals, of whom 72 responded. Serious concerns were expressed over the
      current mechanisms for technology transfer and university support of
      commercialization. When asked if they believed that there is a need for a change
      in the way that universities interact with industry in the US, 86% of the
      respondents replied that they either strongly agreed or agreed that there was,
      indeed, a need for change. Among several areas that might be improved, the
      availability of proof-of-concept facilities and funds for early-stage feasibility
      studies were most often identified as important.

PMID- 30235544
TI  - A Comparison of the Pharmacokinetics and Drug Safety Among East Asian
      Populations.
AB  - Global clinical studies conducted in various countries and regions are
      increasing. Race and extrinsic ethnic factors are key covariates that may affect
      the pharmacokinetics (PK), efficacy, and safety of the drug. Genetic similarity
      among East Asian populations has been confirmed; thus, PK, efficacy, and safety
      in these populations are expected to be similar, but this has not been confirmed.
      This study presents a comparison of PK and safety among East Asians from clinical
      studies sponsored by Pfizer. Four compounds with different characteristics,
      including mechanism of actions and PK profiles, were selected, and retrospective
      PK and safety comparisons in East Asians were conducted. No distinct differences
      were observed in PK and safety across the 4 compounds. These results are
      consistent with previous reports on PK comparisons and meet the expectations
      based on genetic similarity among East Asians. Extrapolation of these findings to
      other compounds should be done with caution, but these results should support the
      consideration of mutual use of clinical data among East Asian countries.

PMID- 30235545
TI  - Local Evaluation and Blinded Central Review Comparison: A Victim of Meta-Analysis
      Shortcomings.

PMID- 30235546
TI  - Coalition Against Major Diseases: Precompetitive Collaborations and Regulatory
      Paths to Accelerating Drug Development for Neurodegenerative Diseases.
AB  - Precompetitive collaborations have been successful in several disease areas and
      industries. Such collaborations are critical to address the gaps and challenges
      in therapeutic development for chronic neurodegenerative diseases. On November 5,
      2012, members of the scientific community, advocates, regulators, industry, and
      government officials met at the US Food and Drug Administration to develop tools
      to expedite drug development and maximize the potential for success in future
      drug trials for Alzheimer disease and Parkinson disease. The meeting established
      that multiple collaborative approaches are essential for accelerating drug
      development. Such approaches include precompetitive data sharing, regulatory
      qualification of biomarkers and clinical outcome assessments, implementation of
      data standards, and development of quantitative drug disease trial models. While
      challenges to collaboration among industry partners are formidable, they are not
      insurmountable. The Coalition Against Major Diseases (CAMD) has several positive
      examples to highlight. This review represents proceedings from CAMD's annual
      conference and discusses the key themes that are being advanced by the Critical
      Path Institute.

PMID- 30235548
TI  - DIA/NORD 2013 US Conference on Rare Diseases and Orphan Products: Poster
      Abstracts.

PMID- 30235547
TI  - New Governance Mechanisms to Optimize Protocol Design.
AB  - Pharmaceutical and biotechnology companies are actively seeking ways to optimize
      protocol design. An emerging approach has been the creation of a new governance
      mechanism designed to evaluate protocol feasibility and simplify design before
      final protocol approval. In late 2012, the Tufts Center for the Study of Drug
      Development conducted a qualitative in-depth assessment of 10 major
      pharmaceutical companies that have implemented these new governance mechanisms
      since 2009. Detailed profiles of each company's feasibility review mechanism are
      discussed including committee missions and objectives, positioning, composition,
      staffing models, reporting flow, implementation challenges, and measured impacts
      to date.

PMID- 30235549
TI  - Editor-in-Chief's Commentary: Collaborative Models for Drug Development,
      Evaluation, and Clinical Use.

PMID- 30235550
TI  - The Multiple Sclerosis Outcome Assessments Consortium: Bringing the Community
      Together to Shape the Future of Multiple Sclerosis Drug Development.

PMID- 30235551
TI  - An Exploratory Study on the Policies of Health Care Institutions in the New
      England Region of the United States Regarding Third-Party Access to Medical
      Records of Research Participants: Potential Effects on the Legal and Ethical
      Conduct of Clinical Trials.
AB  - Source document verification (SDV) is a basic and vital part of monitoring
      activities in clinical trials. In most cases, SDV involves the examination of
      medical records by a third party or an individual who is not an employee of the
      health care institution responsible for medical records storage and maintenance.
      It is therefore vital for health care institutions to ensure that their third
      party access policies are compliant with applicable guidelines, laws, and
      regulations. A quantitative cross-sectional study design using a confidential
      online survey was used to examine policies of health care institutions in New
      England as they pertain to the legal and ethical aspects of third-party access to
      medical records of clinical research participants. A wide variation in
      institutional policies was found, and some were non-compliant with applicable
      laws, regulations, and/or basic ethical principles.

PMID- 30235552
TI  - Statistics, Quality Review Issues, and Beyond for Generic Drug Applications in
      Taiwan.
AB  - The aim of the present study was to investigate the characteristics and
      deficiencies listed in the final quality assessment reports of generic drug
      applications submitted in Taiwan. The basic information of 370 generic drug
      applications submitted from June 2011 to the end of May 2012 was analyzed,
      including the dosage forms, classification, location of manufacturing sites of
      the drug substances and products, as well as deficiencies listed in the final
      quality assessment reports submitted to the Food and Drug Administration,
      Department of Health, Executive Yuan in Taiwan (TFDA) for final decisions before
      the end of September 2012. Statistical analysis demonstrated a variety of
      submissions concerning a manufacturing aspect. The deficiencies were found to be
      similar to common deficiencies observed by the US Food and Drug Administration
      (FDA) and the World Health Organization (WHO), while some issues were mentioned
      by the European Medicines Agency (EMA) as well. The present article is believed
      to be the first report to analyze the basic information of generic drug
      applications in addition to the identification of common deficiencies. These
      findings may provide an overview on the submissions and regulatory considerations
      for generic drug applications in Taiwan, which could be useful for applicants in
      the compilation of their dossiers and could facilitate the approval process.

PMID- 30235553
TI  - Legal Requirements, Definitions, and Standards for Non-interventional Drug
      Studies: A Global Picture of Variability-Results and Conclusions From a Single
      Institution Survey.
AB  - Non-interventional studies (NIS) have become increasingly important in the
      continuous benefit-risk assessment of medicines. However, the diversity in study
      designs and in requirements necessitates a careful planning of NIS. In view of a
      changing regulatory environment, a company-internal online survey was initiated
      to gather information on existing standards, definitions, and requirements for
      NIS and to draw advice for the future conduct of multinational NIS. Answers from
      45 countries worldwide depicted a global picture of variability in terms of legal
      and regulatory requirements for NIS. Definitions and terminology are lacking
      harmonization, and different good practice standards are concurrently in use.
      Variations in terms of applicable standards and requirements were observed within
      most geographic regions. The methodological variety in terms of study designs and
      the divergent perspectives on NIS constitute communicative barriers. Because of
      the absence of one worldwide applicable good practice standard, differences in
      semantics and regulatory systems contribute to system disparities.

PMID- 30235554
TI  - Approvals of Pharmaceutical Drugs in China in the Post-Drug Registration
      Regulation II Era.
AB  - OBJECTIVE: To delineate the impact of the revised Drug Registration Regulation
      (DRR II) issued in 2007 on drug approval in China and reveal the change in
      approval situations for new drugs and generic drugs in the post-DRR II era (2007
      2011). METHODS: Data of drug approvals were collected from the database of the
      China Food and Drug Administration (CFDA) and were analyzed by introducing 3
      ratio indicators and utilizing statistical analysis tools. RESULTS: In the post
      DRR II era, the drug approvals showed a general trend of the following: (1) a
      statistically significant rise in both the absolute number and proportion of new
      drugs, (2) a nonsignificant change for drugs in new dosage forms, and (3) a
      statistically significant drop in both the absolute number and proportion of
      generic drugs. On the other hand, Class 1 (new chemical entities) drugs accounted
      for an extremely small proportion in new drugs. Except for the rise in
      gastrointestinal and cardiovascular new drugs, no significant changes were found
      in other therapeutic categories. CONCLUSIONS: Thanks to the DRR II, the
      aberration in Chinese drug registration has been terminated. Approvals for new
      drugs and high-quality generics are the main trends. Because of the severe
      paucity of Class 1 drugs, innovation and collaboration will be the main 2 themes
      for the Chinese pharmaceutical industry as well as the upcoming version of the
      DRR III in the near future.

PMID- 30235555
TI  - Characterizing Good Review Practices: A Survey Report Among Agencies of APEC
      Member Economies.
AB  - As a first step in the implementation of the Asia-Pacific Economic Cooperation
      (APEC) Best Regulatory Practice Project, the Centre for Innovation in Regulatory
      Science conducted a gap analysis survey among regulatory agencies of 14 APEC
      member economies to assess the current use of good review practices (GRevP) to
      support transparent, consistent, predictable, and good-quality regulatory
      decision making. Although the majority of responding agencies have established
      some form of GRevP, most practices are currently evolving and are applied on an
      informal basis. Most agencies have developed standard operating procedures and
      guidelines and use a variety of training methods. The use of a common approach to
      regulatory review across jurisdictions would help build trust and confidence in
      each agency's processes, setting the stage for the possibility of work sharing
      across resource-constrained agencies and bringing consistency and transparency to
      the review process.

PMID- 30235556
TI  - Overview of the Regulation of Medical Devices and Drugs in the European Union and
      the United States.
AB  - This article provides an overview of the regulation of medical devices and drugs
      in the European Union and the US. It is important for all stakeholders involved
      in bringing a medical device or drugs to market to have an understanding of the
      regulatory requirements involved in this process. This article demonstrates that
      the regulation of these products is an extremely complex process.

PMID- 30235557
TI  - Globalizing Medical Information: The Executive Nurse as a Primary Director.
AB  - Executive nursing leadership is well qualified to direct the global medical
      information functions, however the literature does not specifically support this
      as a reality. This article conceives the challenges of a global medical
      information department while juxtaposing nurse training and leadership. A robust
      premise is established to include the advanced practice registered nurse among
      the list of candidates for executive leadership of the global medical information
      department. Nursing skills are not limited to entry-level medical information
      positions; executive-level competencies are uniform with the executive nursing
      leader. The registered nurse contributes a novel patient care perspective to the
      interdisciplinary team and will provide added value to all activities under the
      governing practices for a global medical information department.

PMID- 30235558
TI  - Investigation Into the Antinfluenza Agent Oseltamivir Distributed via the
      Internet in Japan.
AB  - This study evaluated the quality and authenticity of the anti-influenza agent
      oseltamivir acquired via the Internet in Japan. The brand name drugs Tamiflu and
      Antiflu were obtained via the Internet using a search engine. The authenticity
      and legitimacy of the medicines were verified with the samples' manufacturers and
      the regulatory authorities of the country of origin, respectively. In addition,
      quantitative and dissolution tests were carried out using high-performance liquid
      chromatography. No counterfeits were detected among the samples. Additionally,
      all samples passed qualitative and quantitative tests according to the US
      Pharmacopeia monograph. However, different sorts of mismanagement were observed
      in the distribution channels. Through the Internet, oseltamivir can be purchased
      in quantities larger than the permissible amount in Japan. Furthermore,
      maintenance of medicine quality cannot be guaranteed. In addition, insufficient
      information and lack of quality control in some samples may cause unwanted health
      problems in patients.

PMID- 30235559
TI  - Lipodystrophy Is Common Among Ethiopian Patients on Highly Active Antiretroviral
      Therapy but Is Not Associated With Quality of Life or Medication Adherence.
AB  - Clinical experience suggests that lipodystrophy (LD) can have a profound impact
      on quality of life (QOL) and medication adherence (MA). Thus, a hospital-based,
      cross-sectional study was conducted to determine the prevalence of LD and its
      association with QOL and MA. A total of 405 participants were included in the
      study. The majority of participants were female (64.5%), with a mean age of 35.69
      years (SD = 9.63 years). The prevalence of LD was 30.9%. Multiple logistic
      regression analysis showed that type of regimen initially used is an independent
      predictor of severity of LD (adjusted odds ratio, 44.16; 95% confidence interval,
      10.56-184.59; P = .001). Quality of life was assessed with the World Health
      Organization Quality of Life short form instrument (WHOQOL-BREF), and medication
      adherence was assessed by self-report. The mean WHOQOL-BREF score of the
      participants was 53.48; the highest mean value was in the domain of physical
      health (68.56) and the lowest was in the social relationships domain (47.09). The
      majority of the patients scored lower (ie, in the lowest 5 deciles) in the
      domains of psychological health, social relationships, and environment compared
      with physical health. No differences in the WHOQOL-BREF measurements were
      observed, except in the environment domain, between patients with moderate LD and
      severe LD ( P = .02). The LD severity was not associated with self-reported MA (
      P = .42). With the exception of the psychological health domain ( P = .044),
      participants' WHOQOL-BREF scores were not significantly associated with MA.
      Lipodystrophy was not associated with QOL or MA. The prevalence of LD in the
      present study was within the range of previous reports; however, the mean WHOQOL
      BREF score of Ethiopian patients in this study is lower compared with reports
      from developed countries.

PMID- 30235561
TI  - Editor-in-Chief 's Commentary: The Changing Landscape of Drug Companies.

PMID- 30235560
TI  - Rheumatoid Arthritis Disease Progression Modeling.
AB  - Time progression models provide a significant advantage in developing clinical
      trials and can also be used to elicit comparisons among therapeutic agents. The
      authors performed a meta-analysis to construct a time progression model for
      rheumatoid arthritis (RA), an area of significant interest for pharmaceutical
      development, using the ACR20 end point. Compounds studied were chiefly monoclonal
      antibodies that were used in conjunction with methotrexate. The study shows that
      an exponential time response model adequately fits the data. From the modeling, a
      distribution of effects for biological RA therapies can be provided.

PMID- 30235562
TI  - Statistical Properties of Large Sample Tests for Dose Content Uniformity.

PMID- 30235563
TI  - Biopharmaceutical Contact Centers and Combination Products: Results of a
      Benchmark Survey.
AB  - Biopharmaceutical contact centers are expanding core skill sets when it comes to
      addressing inquiries regarding combination products. An inside look at how
      biopharmaceutical companies are handling this increasingly common scenario is
      provided through a benchmark survey, which was conducted between December 2012
      and January 2013. The purpose of this survey was to collect and share contact
      center best practices on the handling of combination products in the
      biopharmaceutical industry. Eleven biopharmaceutical companies participated in
      the survey, 10 of which were listed in "The Top 50 Pharmaceutical Companies," by
      Pharmaceutical Executive. The information gathered from the survey responses is
      reported anonymously and provides perspectives on the trends and best practices
      that will serve as a practical resource for those involved in establishing or
      expanding contact center services.

PMID- 30235564
TI  - Teratogenic Drugs and Risk Management: An Implementation Assessment.
AB  - About half of all pregnant women are prescribed medication during their
      pregnancy, including drugs with teratogenic potential. There is a need to manage
      teratogenic risk and prevent fetal harm. In the US, risk management strategies
      may range from product labeling to the US Food and Drug Administration requiring
      a risk evaluation and mitigation strategy, including elements to assure safe use.
      The resources of these risk management controls on the health care system must be
      weighed against the benefits of preventing embryo-fetal exposure and birth
      defects. This article describes considerations for determining which risk
      mitigation strategies to use with teratogenic drugs and the challenges and
      opportunities to balance restrictions and burdens with the benefit of access to
      important drugs.

PMID- 30235565
TI  - Compliance Within Medical Information and the Emergence of a Medical Information
      Dedicated Compliance Person: A Benchmarking Survey.
AB  - In light of the increasing scrutiny by governing authorities, compliance
      requirements for medical information (MI) departments have increased over the
      past few years. In response to the Food and Drug Administration (FDA) draft
      guidance for industry, entitled Responding to Unsolicited Requests for Off-label
      Information About Prescription Drugs and Medical Devices, MI groups may be
      changing their policies and procedures to further ensure compliance. The primary
      objective of this study was to benchmark industry-specific practices related to
      maintaining compliance in MI, particularly whether there is an emergence of a
      dedicated compliance person working within the MI department, whom we refer to as
      the MI-dedicated compliance person hereafter. A secondary objective was to
      identify changes to MI interactions with internal and external stakeholders that
      occurred in the last 2 years in response to an evolving regulatory climate. A web
      based survey was disseminated to MI professionals from 49 companies between
      December 2012 and February 2013. Practices that were assessed include MI team
      training, monitoring, audits, and creation of letter responses. The results may
      be useful for MI groups interested in changing or comparing their compliance
      practices to those currently utilized by their peers.

PMID- 30235566
TI  - Consideration of Factors Affecting the Safety Index in Early Clinical Drug
      Development.
AB  - In drug development, a safety index-the ratio of the highest exposure that does
      not induce toxicity to the exposure that exerts efficacy-is used to quantify the
      balance between the safety and efficacy of a test drug. Here, the phase 1 index
      (maximum area under the curve [AUC] in phase 1/therapeutic AUC) and no-observed
      adverse-effect level (NOAEL) index (AUC at NOAEL/therapeutic AUC) of recently
      approved drugs in Japan were calculated and characterized by therapeutic areas
      and indications. A large variation within both indices was observed, with a
      median of 3.2 for the phase 1 index and 3.5 for the NOAEL index. Furthermore, the
      safety indices were affected by the therapeutic area, which might be attributed
      to the difference in unmet medical needs for certain diseases. This study
      provides a qualitative measure for interpreting the phase 1 index versus the
      NOAEL index and might help inform the decision-making process following phase 1
      trials.

PMID- 30235567
TI  - Interconnectivity of Disparate Nonclinical Data Silos for Drug Discovery and
      Development.
AB  - Pharmaceutical research and development generates enormous amounts of nonclinical
      and clinical data related to safety and efficacy, and the ability to manage and
      utilize these data is critical for discovering and developing new drugs.
      Information systems exist that store and analyze relationships among seemingly
      disparate data sets (ie, data silos); however, to fully utilize the potential of
      these informatics systems, it is necessary to define basic parameters about the
      data and to develop concepts regarding "interconnectivity," or relationships
      among disparate data sets. To explore these issues, the Nonclinical Data
      Interconnectivity Sub-Group was chartered: a component of the Non-Clinical Road
      Map and Impacts on Implementation Working Group associated with the US FDA-PhUSE
      (Pharmaceutical Users Software Exchange) Computational Sciences initiative. As a
      starting point, the group defined the meaning of data interconnectivity.
      Nonclinical data types were then identified and challenges and opportunities for
      interconnectivity explored. Specific-use cases were identified to provide
      examples of the value for interconnecting data across disciplines or silos.

PMID- 30235568
TI  - Key Considerations in the Transition to Risk-Based Monitoring.
AB  - In the 2 years since publication of the European Medicines Agency's "Reflection
      Paper on Risk Based Quality Management in Clinical Trials" and US Food and Drug
      Administration's "Draft Guidance for Industry: Oversight of Clinical
      Investigations-A Risk-Based Approach to Monitoring," the methodologies, products,
      and services for risk-based monitoring have proliferated and diversified. The
      biopharmaceutical industry can choose from a variety of general approaches and
      specific practices. This article provides a framework to assist biopharmaceutical
      companies in selecting and implementing a risk-based monitoring approach or
      selecting a service provider. The framework includes discussion of different
      approaches to source data verification but also discusses other important
      dimensions of risk-based monitoring: individualization of the monitoring approach
      for each study; error detection and correction, including but not limited to
      source data verification; real-time quality management; error prediction and
      prevention; and adoption and implementation.

PMID- 30235569
TI  - The Impact of Collaborative and Risk-Sharing Innovation Approaches on Clinical
      and Regulatory Cycle Times.
AB  - During the past decade, high risk, cost, and inefficiency have driven
      pharmaceutical and biotechnology companies to enter into collaborative and shared
      innovation approaches, including mergers and acquisitions, joint development, and
      in-licensing. These approaches can interrupt the drug development process and
      affect program-level clinical and regulatory cycle times. To examine these
      potential impacts, detailed development histories were obtained for 289 new
      molecular and biologics entities that received FDA approval between 2000 and
      2011. Approximately half the drugs analyzed had their clinical development
      activity interrupted by a collaborative or shared innovation approach, with in
      licensing as the most common. The total duration (clinical plus approval phases)
      for interrupted development programs was 20% longer-an additional 14.8 months
      (median)-than that of uninterrupted development programs ( P < .05). Approval
      phase length differences between uninterrupted and interrupted programs were not
      statistically significant. The results of this study provide important benchmarks
      and new insights for portfolio planning, forecasting, and management.

PMID- 30235570
TI  - Adaptive Design: Results of 2012 Survey on Perception and Use.
AB  - Adaptive designs are increasingly used in clinical trials. The Drug Information
      Association's Adaptive Design Scientific Working Group (ADSWG) works to foster
      collaboration among regulatory agencies, academia, and pharmaceutical and biotech
      companies to further the science of adaptive clinical development. The ADSWG
      Survey Subteam has collected data on the usage of adaptive designs in clinical
      research from multiple sources, including a recent ADSWG survey regarding the
      perception and usage of adaptive designs in academia and industry for studies
      between 2008 and 2011, as well as barriers to usage; a literature review
      examining publications of adaptive design methodology and usage between 2000 and
      2011; and a trial registry review of adaptive design references from 1996 to
      2011. The comprehensive results of the ADSWG 2012 survey are provided in this
      article with comparisons to our previous 2008 survey, the literature and registry
      reviews, and recent surveys carried out by the US Food and Drug Administration
      (FDA) and the European Medicines Agency. Results of the ADSWG 2012 survey
      illustrate that industry and academia are showing more enthusiasm for adaptive
      trials, accompanied by an increase in the number of trials using designs
      described as less well understood in the FDA draft guidance on adaptive designs,
      published in 2010. The increased use of these methods in exploratory trials is
      consistent with the FDA draft guidance. The survey also identified several
      examples of successful marketing applications supported by confirmatory trials
      utilizing adaptive designs that were considered, at least at the time of the
      draft guidance, as less well understood. While some of the technological barriers
      to adaptive design usage identified in the 2008 survey are now less common, there
      are several important persistent barriers to usage. Organizations can help
      overcome these barriers through education, preplanning, and early engagement in
      discussions with the regulators.

PMID- 30235571
TI  - Academic Clinical Trials and Drug Regulations in Japan: Impacts of Introducing
      the Investigational New Drug System.
AB  - In Japan, academic clinical trials do not generally need to be conducted under
      good clinical practice and cannot therefore be used for regulatory submission for
      marketing authorization of new medical products. We reviewed 2 differential
      regulatory systems governing clinical trials in Japan and the development
      histories of 2 case products whose clinical trials at the early development stage
      were conducted by academic researchers and transferred to the private sector for
      further development toward commercialization in Japan. We further estimated that
      the introduction of the investigational new drug system may have accelerated the
      development of tocilizumab, an antibody drug for rheumatoid arthritis, at best by
      2 years by utilizing the results of early exploratory clinical trials conducted
      by academic investigators. Similarly, an enlarged indication for JACE(r), a
      cultured epithelium autograft for severe burns, would have been expected at
      launch by utilizing the results of academic trials investigating various
      indications. These possible impacts and estimations would warrant introducing the
      investigational new drug system into Japan drug regulatory system.

PMID- 30235572
TI  - Multipopulation Tailoring Clinical Trials: Design, Analysis, and Inference
      Considerations.
AB  - Several recent publications have focused on statistical considerations that arise
      in multipopulation tailoring clinical trials that evaluate treatment effect in an
      overall patient population as well as one or more predefined subpopulations. This
      paper presents a decision-making framework applicable to these trials and
      evaluates the operating characteristics of this framework versus one based solely
      on the results of primary hypothesis tests. The operating characteristics are
      presented as rates of applicable errors, known as influence errors and
      interaction errors.

PMID- 30235573
TI  - A Bayesian Stopping Rule for Sequential Monitoring of Serious Adverse Events.
AB  - In an ongoing clinical trial, there will always be a risk for unanticipated
      critical safety problems, such as excessive occurrence of serious adverse events.
      When such a problem arises, the trial administrators must conduct an immediate
      evaluation to determine whether the trial should be terminated to protect
      patients. This decision is complicated but may be aided by statistical stopping
      rules. Sequential stopping rules are appropriate for immediate decisions, but
      frequentist approaches may not be useful because the unknown truncated end of the
      trial makes it impossible to define type I errors. Thus, a Bayesian stopping rule
      is proposed that is based on the posterior distribution with an informative prior
      distribution, and a guideline to construct this stopping rule is presented. Some
      operating characteristics are evaluated and compared with those of the modified
      sequential probability ratio test (SPRT), the maximized SPRT, and Pocock's test.
      The proposed method has flexibility for construction and could provide a more
      desirable performance than the other compared methods.

PMID- 30235574
TI  - A Systematic Literature Review on the Assessment of Palatability and
      Swallowability in the Development of Oral Dosage Forms for Pediatric Patients.
AB  - BACKGROUND: Palatability and swallowability of oral dosage forms are important
      considerations in the development of medications for pediatric populations. As a
      result of recent legislation, the number of pharmaceutical products being
      developed with formulations for children is increasing. However, there are
      limited recommendations and published literature regarding appropriate
      palatability and swallowability assessment scales in pediatric patients.
      OBJECTIVE: This systematic literature review aimed to identify and evaluate tools
      currently utilized to assess palatability and swallowability in clinical trials
      for pediatric oral dosage forms and identify any potential relationships between
      palatability and treatment adherence. Literature databases were searched for
      clinical trials that evaluated palatability of oral dosage forms targeted for
      pediatric patients. The searches were limited to papers in the English language
      from January 2008 to March 2013. RESULTS: A total of 137 citations were
      identified, with 27 articles included in the final full-text analysis.
      CONCLUSIONS: Various limitations to this systematic review exist, primarily
      focused on the unavailability of published, early phase development data related
      to palatability. However, based on results of this review, palatability is often
      assessed in clinical trials of pediatric dosage forms through the utilization of
      2 unvalidated, yet widely accepted, visual scales. There is no standard
      statistical methodology for analyzing the results of these scales or the cross
      comparison of results across studies. Limited evidence regarding a correlation
      between palatability and treatment adherence in pediatric patients was
      identified.

PMID- 30235575
TI  - A Modeling and Simulations Framework to Support Global Regulatory Strategies for
      Pediatric Drug Development Programs.
AB  - Trial simulations have emerged as a promising tool to optimize pediatric drug
      development programs. As the current FDA legislation on pediatric drugs and
      devices was updated to mirror the EMA legislation, pediatric programs must be
      developed with global strategies that support a Pediatric Investigation Plan
      (PIP) for the EMA and a Pediatric Study Plan (PSP) for the FDA. A pharmacometrics
      framework is proposed to support global regulatory strategies for pediatric drug
      development programs. The framework describes specific trigger points and
      opportunities for applying modeling and simulation techniques to design the PIP
      and PSP and ultimately optimize pediatric drug development programs. The
      development of pediatric protocols by simulations and execution plans is deemed
      critical in defining expectations and ensuring the future success of these global
      programs. This can lead to clinical trial designs that are more efficient, less
      prone to failure, and ultimately, less costly.

PMID- 30235576
TI  - Medicines in Pregnancy-Women and Children First? Time for a Coalition to Address
      a Substantial Patient Need.

PMID- 30235577
TI  - Role of Patient-Reported Outcome Measures in the Assessment of Central Nervous
      System Agents.
AB  - This work aimed to provide an understanding of the current use and regulatory
      acceptability of patient-reported outcome (PRO) measures in labeling claims for
      central nervous system (CNS) agents. A subset of CNS agents was identified from
      all New Drug Approvals and Biologic License Applications for new drugs approved
      in the US from January 2006 to June 2012. Clinician-reported outcomes (ClinROs)
      (62%) and PROs (38%) were the most widely used primary outcome measures. The PROs
      were frequently used in combination with ClinROs. Twelve PRO claims were granted
      across 41% of CNS drug approvals: 83%, symptoms; 17%, functioning. The PROs are
      frequently utilized as primary and secondary end points in CNS agents, and
      labeling claims are granted at higher levels than for non-CNS agents (41% vs 24%,
      respectively). These claims are granted at a lower rate than expected, given that
      direct patient input may lend valuable insight to treatment impacts in most CNS
      diseases.

PMID- 30235578
TI  - Industry Survey on Current Practices in the Assessment of Palatability and
      Swallowability in the Development of Pediatric Oral Dosage Forms.
AB  - An industry-based survey was conducted by the Global Alliance for Pediatric
      Therapeutics in February 2013 to determine and evaluate the current industry
      practices in the assessment of palatability and swallowability during the
      development of pediatric oral solid dosage forms, including the design and
      statistical analysis of such studies. In addition, the survey was designed to
      identify areas where regulatory guidance is most needed. The survey was
      distributed to 6 research-based pharmaceutical companies and to members of the
      American Academy of Pediatrics' Provisional Section on Advances in Therapeutics
      and Technology. In general, while all responding companies have experience
      developing pediatric medicines, there was no consistent approach among
      respondents to the assessment of organoleptic properties of solid dosage forms,
      including excipients. In the direct assessment of palatability in pediatric
      patients in clinical trials, the survey identified that a variety of methods is
      used across companies, including visual analogue scales, simple and complex
      hedonic scales, and simplistic Likert-type scales. No assessment method
      identified was acknowledged as validated or with any statistical correlates, with
      many respondents stating that scales used in the pharmaceutical industry are
      adapted from the significant work conducted in the food service industry. Based
      on findings from the industry survey, the authors believe that there is an
      opportunity for consensus of the assessment of palatability and swallowability in
      the development of pediatric oral solid dosage forms.

PMID- 30235579
TI  - Editor-in-Chief's Commentary: Women and Children First.

PMID- 30235580
TI  - Quantitative Extrapolation: An Approach to Validation of Adult Drug Efficacy in
      Pediatric Subjects.
AB  - Confirmation of efficacy in pediatric drug development has traditionally required
      large, fully powered efficacy studies that have proven to have major feasibility
      and ethical challenges. Extrapolation of efficacy in the framework provided by
      the US Food and Drug Administration and European Medicines Agency is an
      appropriate solution when there is similarity of disease. When there is
      uncertainty regarding the degree of disease similarity, partial extrapolation may
      be utilized. The authors propose a more quantitative approach to partial
      extrapolation (ie, quantitative extrapolation), involving (1) integration of
      adult pharmacokinetic (PK), pharmacodynamic (PD), and clinical outcome data using
      pharmacometric models, (2) extrapolation using the adult pharmacometric model to
      predict PD and efficacy outcomes in pediatric subjects, and (3) validation of
      pediatric predictions with a streamlined plan of pediatric trials (ie, a
      quantitative extrapolation plan). A case study is presented for quantitative
      extrapolation using dipeptidyl peptidase 4 (DPP-4) inhibitors. In this example,
      the authors demonstrate how adult PK, PD, and HbA1c data can be integrated using
      a pharmacometric model for DPP-4 inhibitors with pediatric dose selection and
      efficacy validated with relatively few pediatric subjects.

PMID- 30235582
TI  - The ICH, the GHTF, and the Future of Harmonization Initiatives.
AB  - Comparison of the International Conference on Harmonisation of Technical
      Requirements for Registration of Pharmaceuticals for Human Use (ICH) and the
      Global Harmonization Task Force (GHTF), the global regulatory harmonization
      initiatives in the field of drugs and medical devices, respectively, reveals that
      "harmonization" activities contain several categories. It was also found that the
      target level of harmonization (ie, that of technical regulatory requirements and
      that of regulatory processes) greatly affects the implementability of final work
      products. Those products concerning regulatory processes (most of the GHTF
      Documents) often require legal changes and are more difficult to implement than
      those regarding technical requirements (all of the ICH Guidelines), usually
      implementable by regulatory authorities publishing them as nonbinding
      suggestions. Globalization of medical product development, manufacture, and
      distribution increasingly requires regulatory cooperation across borders, which
      inevitably affects the initiatives. Identifying what "harmonization" each
      harmonization initiative aims at is indispensable in determining future
      directions.

PMID- 30235581
TI  - Pediatric Pharmacovigilance: Enhancing Adverse Drug Reaction Reporting in a
      Tertiary Care Children's Hospital.
AB  - BACKGROUND: Adverse drug reactions (ADRs) are notoriously underreported within
      health care facilities. In 2009-2010, ADRs were detected in only 0.5% of patients
      at the authors' institution, a pediatric hospital in the Midwestern United
      States. Additionally, historical ADRs were often inaccurately or incompletely
      documented in the medical record. An integrative Drug Safety Service (DSS) was
      implemented to improve the detection and accurate documentation of ADRs. METHODS:
      The DSS incorporated standardized ADR terminology, computerized triggers to
      identify ADRs, and a simplified voluntary reporting system within the facility.
      The DSS staff provided extensive hospital staff education on ADR reporting and
      the role of the DSS. The primary aim of this report was to assess the impact of
      the DSS on the number of ADRs reported at the authors' institution. The secondary
      aims were to evaluate the mechanisms by which patients with ADRs were identified
      and to assess the accuracy of ADR documentation after implementation of the DSS.
      RESULTS: A significant increase was observed (slope, 6.01; P < .001) in ADR
      detection after implementation of the DSS, with a greater than 4-fold increase
      from 10 cases per 10,000 admissions before initiation to 41 cases per 10,000
      admissions after DSS implementation. Computerized triggers, International
      Classification of Diseases, 9th Edition (ICD-9) codes associated with ADRs, and
      the DSS identified 33%, 33%, and 24% of ADRs, respectively, while voluntary
      reporting only detected 9% of ADRs. CONCLUSIONS: Implementation of a
      multifaceted, interdisciplinary DSS was more effective in detecting ADRs than
      voluntary reporting alone. A proactive approach to ADR detection resulted in a
      significant increase in the identification and evaluation of ADRs.

PMID- 30235583
TI  - Regulations of Medical Devices in Regulated Countries: A Comparative Review.
AB  - The term "medical device" covers a vast range of equipment, from simple tongue
      depressors to hemodialysis machines. Like medicines and other health
      technologies, they are essential for patient care. With the increased use of
      medical devices, stringent regulatory standards are required to ensure that the
      devices are well studied, safe, and well tolerated. Recently, introduced
      guidelines and amendments in the laws of the US, Europe, and Canada provide
      adequate guidance for both manufacturers and competent authorities to prevent
      defects and performance failures efficiently and appropriately. A defective
      device may result in inaccurate patient results, leading to misdiagnosis, delays
      in treatment, adverse events, injuries, or even death. Therefore, a thorough
      review of the medical device before being released for use by the public and
      effective monitoring of the medical device once placed on the market are crucial.

PMID- 30235584
TI  - Process Investigation of a Novel Compaction Technique With Pellet-Containing
      Granules.
AB  - OBJECTIVE: The purpose of this study was to investigate the influence of the
      preparing process on the properties of pellet-containing granules and tablets.
      METHODS: Coated pellets were granulated by centrifugal granulation, and the
      obtained pellet-containing granules were mixed with cushioning granules and
      compressed into tablets. Tablets were characterized for a drug release rate as
      compared with the original coated pellets. RESULTS: The surface roughness and the
      angle of repose of pellet-containing granules increased with the granulating
      ratio. Weight and drug content variations in tablets were diminished by
      granulation, and great improvement in tablet uniformity was achieved even for
      large pellets. Granulation showed protection for coated films under different
      compress forces and at even a low content of cushioning granules. CONCLUSIONS:
      The uniformity of tablets prepared from pellet-containing granules could be
      significantly improved by the granulation process at a proper granulating ratio.
      The granulation process could protect the coated pellets during compaction even
      under high compression forces and with a low content of cushioning granules.

PMID- 30235585
TI  - Improving Oncology Clinical Programs by Use of Innovative Designs and Comparing
      Them via Simulations.
AB  - The design of an oncology clinical program is much more challenging than the
      design of a single study. The standard approach has been proven to be not very
      successful during the past decade; the failure rate of phase 3 studies in
      oncology is about 66%. Improving the development strategy by applying innovative
      statistical methods is one of the major objectives for study teams designing and
      supporting oncology clinical programs. However, evaluating trial design
      alternatives is difficult; the designs may have different advantages-better
      power, better type I error control, shorter duration, or more accuracy-and their
      relative performance may depend on assumptions about the drugs' performance.
      Evaluating different early phase designs in particular suffers from both these
      problems. This paper is built on the work of the DIA's Adaptive Design Scientific
      Working Group oncology subteam on an Adaptive Program. With representatives from
      a number of institutions, this group compared 4 hypothetical oncology development
      programs that each was to select between 2 treatments and decide whether to
      proceed to phase 3, using probability of the clinical program's success and
      expected net present value (eNPV). Simulated scenarios were used to motivate and
      illustrate the key ideas. For the development strategies, we believed that the
      eNPV showed a distinct and robust improvement for each successive strategy.

PMID- 30235586
TI  - Occurrence, distribution and behavior of emerging persistent organic pollutants
      (POPs) in a Mediterranean wetland protected area.
AB  - The analysis of perfluoroalkyl substances (PFASs) and organophosphate flame
      retardants (PFRs) in the different environmental compartments of a characteristic
      coastal wetland, the Albufera Natural Park (Valencia, Spain), is required for
      understanding the transport, accumulation and fate of these pollutants in an area
      under high anthropogenic pressure. Samples included 13 wastewater treatment plant
      influents, 13 effluents, 12 surface water, 19 sediment samples and 10 fish
      individuals from the Albufera Natural Park and the surrounding area. Tris(2
      chloroisopropyl) phosphate (TCIPP) and perfluorooctane sulfonate (PFOS) were at
      the highest concentrations in water, 330.2 ng L-1 and 47.8 ng L-1, respectively.
      In fish and sediment PFOS was also the most detected while perfluorooctanoic acid
      (PFOA) was in all types of water. Higher levels of target compounds (mainly
      PFASs) in wastewater effluents compared to influent suggested both, formation
      from precursors during treatment and poor removal efficiency. Mean levels of PFOS
      in water and fish were higher than the environmental quality standards (EQS)
      established by the European Union Directive 2013/39/EU. The influence of the
      metropolitan area of Valencia and its surrounding industrial belt could explain
      the significantly higher levels reported in the northern part (influenced by the
      Turia River).

PMID- 30235587
TI  - Ambient temperature, sunlight duration, and suicide: A systematic review and meta
      analysis.
AB  - BACKGROUND: The relationship between sunlight hours, temperature, and suicide has
      been investigated in many previous studies, but with inconsistent findings. We
      conducted this meta-analysis aiming at providing clear evidence about whether
      sunlight hours and temperature can affect the risk of suicide. METHODS: Relevant
      literature published before 7 Jul 2018 was searched in three electronic database
      of PubMed, Web of science and Cochrane. Between-study heterogeneity in the effect
      estimates were examined by study design (i.e., exposure time resolution,
      temperature measure and suicide classification) and population vulnerability
      (i.e., sex, national income level, climate zone and study location). RESULTS:
      Regarding temperature-suicide association, we identified 14 studies that provided
      23 effect estimates for meta-analysis. Our random-effects model showed that each
      1  degrees C increase in temperature was significantly associated with a 1%
      increase in the incidence of suicide (Incidence Rate Radio (IRR) = 1.01; 95%CI =
      1.00-1.02; p < 0.05). As for sunlight duration and suicide, 11 effect estimates
      from 4 studies were pooled using a fixed-effects model. Significant association
      between sunlight duration (per 1 h increase) and the risk of suicide was not
      observed, and the pooled IRR was 1.00 (95%CI = 0.99-1.01; p > 0.05). There was
      significant heterogeneity between previous studies' effect estimates, and
      significantly lower heterogeneity was noted for the female group, for studies
      that did analyses at daily scale, and for studies using mean temperature as the
      exposure indicator. CONCLUSION: Our findings suggest a significant and positive
      association between temperature rises and incidence of suicide, and a non
      significant association between sunlight duration and incidence of suicide.
      Populations living in tropical and temperate zones or at middle-income level may
      be particularly vulnerable to temperature increase.

PMID- 30235588
TI  - Association between short-term exposure to fine particulate matter and daily
      emergency room visits at a cardiovascular hospital in Dhaka, Bangladesh.
AB  - BACKGROUND: It has been suggested that exposure to fine particulate matter
      (PM2.5) adversely affects cardiovascular health. However, the effect
      modifications by individual characteristics and season have been less studied in
      developing countries where PM2.5 levels are high. OBJECTIVES: To estimate the
      risks of cardiovascular emergency room visits in relation to daily concentrations
      of PM2.5 and to assess how these associations can be modified by age, sex, and
      nutritional status of patients and by season. METHODS: The analytic sample was
      6774 adults who visited the emergency room at a cardiovascular disease (CVD)
      hospital in Dhaka throughout one year (n = 364 days). A time-stratified case
      crossover design with conditional Poisson regression analysis was used to
      estimate the relative risks (RRs) and 95% confidence intervals (CIs) of visits
      while adjusting for temperature. Stratification was performed by gender, age (<65
      and >=65 years), BMI (underweight, normal weight, overweight), and season (dry
      summer: February to April; wet summer: May to October; dry winter: November to
      January). RESULTS: The mean concentration of PM2.5 was 86.1 MUg/m3. An IQR
      increase (103 MUg/m3) in PM2.5 at lag 3 was significantly associated with a 12%
      (RR: 1.12; 95% CI: 1.01-1.23) increase in CVD emergency room visits. No evidence
      of association was found for the other lags. Underweight and overweight patients
      showed evidence of increased risk at lag 2 (RR: 1.31; 95% CI: 1.02-1.67) and lag
      4 (RR: 1.20; 95% CI: 1.04-1.39), respectively. CONCLUSION: Increases in the daily
      concentrations of PM2.5 may lead to more cardiovascular emergency room visits in
      Dhaka, Bangladesh. Response times from ambient exposure to CVD emergency visits
      may differ by season and the nutritional status of susceptible individuals,
      necessitating further research.

PMID- 30235589
TI  - Past and recent state of sediment contamination by persistent organic pollutants
      (POPs) in the Rhone River: Overview of ecotoxicological implications.
AB  - Twenty-one sediment samples were taken from five dated sediment cores collected
      along the Rhone River from 2008 to 2011. A total of 17 polychlorinated dibenzo-p
      dioxins and dibenzofurans (PCDD/Fs), 7 polychlorinated biphenyls (PCBs), 8
      polybrominated diphenyl ethers (PBDEs), 3 polybrominated biphenyls (PBBs), 3
      hexabromocyclododecanes (HBCD) and 31 organochlorine pesticides (OCPs) were
      investigated to provide information on deposition dynamics in time and space, but
      also regarding the ecotoxicological risks associated with these contaminants.
      Median concentrations of total PBDEs are nine times lower than the levels of
      total PCBs along the entire studied stretch of the Rhone River. The results show
      that total PBDEs concentrations range from 0.06 to 239 MUg.kg-1 DW with a median
      value of 3.81 MUg.kg-1 DW and a maximum concentration measured in the years
      2000s. These maximum concentrations are identical to those measured for total
      PCBs at the end of the 1990s, but show a different pattern of distribution.
      Abnormal dichlorodiphenyltrichloroethane (DDT) levels were also detected in the
      downstream section of the river, with a peak concentration of 147.5 MUg.kg-1 DW
      measured at the GEC site from 2005 onwards. Analyses of the enantiomeric
      fractions reveal a fresh input resulting from a technical formulation. Sediments
      from the core sampled at the most downstream site (GEC) are found to be highly
      toxic to organisms living nearby, particularly because of the total PCDD/Fs, DDE
      and DDT levels. In addition, based on available sediment quality guidelines,
      there may be a potential bioaccumulation risk for humans not only for these three
      compounds of concern but also for total PCBs and 7 out of the 8 analysed PBDEs.

PMID- 30235590
TI  - SIRT1 downregulation mediated Manganese-induced neuronal apoptosis through
      activation of FOXO3a-Bim/PUMA axis.
AB  - Manganese (Mn) is an essential trace element. Excessive exposure to Mn may lead
      to neuronal death and neurodegenerative disorders. Accumulating evidence has
      shown that silent mating type information regulation 2 homolog 1 (SIRT1) plays a
      vital role in brain damage. However, whether aberrant SIRT1 levels contribute to
      Mn-induced neurotoxicity remains unknown. In this study, we report the important
      role of SIRT1 downregulation during Mn-induced neuronal apoptosis. Mn was found
      to downregulate SIRT1 protein levels in the rat pheochromocytoma (PC12) cells and
      mouse brain tissues. Mn enhanced SIRT1 protein degradation and downregulated its
      gene expression. Furthermore, Mn induced cell apoptosis in a dose-dependent
      manner both in vitro and in vivo, and resulted in an increase in forkhead box O
      (FOXO) 3a expression and acetylation. SIRT1 activation by resveratrol clearly
      attenuated Mn-triggered apoptosis and FOXO3a activation. Mn markedly increased
      the expression of Bcl-2 interacting mediator of cell death (Bim) and p53-up
      regulated modulator of apoptosis (PUMA), whereas downregulation of FOXO3a
      significantly inhibited their upregulation and subsequent apoptosis. In summary,
      we determined that Mn downregulated SIRT1 by multiple mechanisms, thus led to
      apoptosis via activation of the FOXO3a-Bim/PUMA axis in PC12 cells. These
      findings on the impact of Mn on SIRT1 may lead to an improved understanding of Mn
      induced neurotoxicity and provide a molecular target to antagonise Mn-associated
      neuronal damage.

PMID- 30235591
TI  - Pesticide residues remaining in soils from previous growing season(s) - Can they
      accumulate in non-target organisms and contaminate the food web?

PMID- 30235592
TI  - Mandibular shape in farmed Arctic foxes (Vulpes lagopus) exposed to persistent
      organic pollutants.
AB  - We investigated if dietary exposure to persistent organic pollutants (POPs)
      affect mandibular asymmetry and periodontal disease in paired male-siblings of
      Arctic foxes (Vulpes lagopus). During ontogeny, one group of siblings was exposed
      to the complexed POP mixture in naturally contaminated minke whale (Balaenoptere
      acutorostarta) blubber (n = 10), while another group was given wet feed based on
      pig (Sus scrofa) fat as a control (n = 11). The ?POP concentrations were 802 ng/g
      ww in the whale-based feed compared to 24 ng/g ww in the control diet. We
      conducted a two-dimensional geometric morphometric (GM) analysis of mandibular
      shape and asymmetry in the foxes and compared the two groups. The analyses showed
      that directional asymmetry was higher than fluctuating asymmetry in both groups
      and that mandibular shape differed significantly between the exposed and control
      group based on discriminant function analysis (T2 = 58.52, p = 0.04, 1000
      permutations). We also found a non-significantly higher incidence of periodontal
      disease (two-way ANOVA: p = 0.43) and greater severity of sub-canine alveolar
      bone deterioration similar to periodontitis (two-way ANOVA: p = 0.3) in the POP
      exposed group. Based on these results, it is possible that dietary exposure to a
      complexed POP mixture lead to changes in jaw morphology in Arctic foxes. This
      study suggests that extrinsic factors, such as dietary exposure to POPs, may
      affect mandibular shape and health in a way that could be harmful to wild Arctic
      populations. Therefore, further studies using GM analysis as an alternative to
      traditional morphometric methods should be conducted for wild Arctic fox
      populations exposed to environmental contaminants.

PMID- 30235594
TI  - Impact of salinity on the population dynamics of microorganisms in a membrane
      bioreactor treating produced water.
AB  - Biomass characteristics may change subject to a salinity increase when treating
      high strength wastewater. In this study, the impact of salinity in a membrane
      bioreactor (MBR) was investigated for the treatment of produced water (PW). MBR
      was operated as a pre-treatment prior to nanofiltration (NF) and reverse osmosis
      (RO). Mixed PW, that was originated from different oil, gas, and oil-gas wells,
      were subjected to pre-treatment for 146 days including three different
      operational phases: Low-salinity (~10 mS/cm), gradual increased salinity (10-40
      mS/cm) and high salinity (~40 mS/cm). The results of this study showed that
      microorganisms could adapt using real wastewater and treat PW up to a certain
      level of the salinity. At high salinity levels of PW, the floc structure started
      to be disrupted and membrane fouling was accelerated. PCR-DGGE analysis confirmed
      the changes in microbial communities' composition in relation with high salinity.
      The results of the final treatment experiments presented that NF and RO treatment
      produced high-quality effluents that could be suitable for reuse.

PMID- 30235593
TI  - rDNA- and rRNA-derived communities present divergent assemblage patterns and
      functional traits throughout full-scale landfill leachate treatment process
      trains.
AB  - Understanding the influences of microbial interactions and niche heterogeneities
      on microbial communities and functional traits is critical for determining its
      engineering and ecological significance. However, little is known about microbial
      community assemblage and functional gene expression throughout full-scale
      landfill leachate treatment plants. Here, we applied a combination of 16S rRNA
      and rDNA amplicon sequencing, shotgun metagenomic, and qPCR approaches to unveil
      the ecological associations between distinct communities, functional gene
      expression and nitrogen cycling processes. By comparing the rDNA and rRNA-derived
      communities, the rRNA/rDNA ratios suggested that 57.2% of rare taxa were active,
      and their abundance decreased as increasing of potential activities. In
      particular, rDNA- and rRNA-based communities exhibited divergent assemblage
      patterns, and stronger intra-associations among core taxa in the rRNA-based
      communities than in rDNA-based communities. Furthermore, results regarding both
      bacterial assemblage and functional traits indicated that the habitat filtering
      and niche differentiation (treatment units) exerted selection on microbial
      communities based on functional traits, particular for key ecological functions
      related to nitrogen cycling. Collectively, our findings provide insights into
      structure-function associations at the local level and shed light on ecological
      rules guiding rDNA- and rRNA-based community assembly in landfill leachate
      treatment systems.

PMID- 30235595
TI  - The non-negligible environmental risk of recycling halogenated flame retardants
      associated with plastic regeneration in China.
AB  - To investigate halogenated flame retardant (HFR) contents in recycled plastic
      materials, 23 recycled plastic samples manufactured in five Chinese provinces
      were randomly purchased online, and the ?12HFR concentrations of these samples
      (including 8 polybrominated diphenyl ethers (PBDEs, BDE 28, 47, 99, 100, 154,
      153, 183 and 209), decabromodiphenylethane (DBDPE), 1,2-bis(2,4,6
      tribromophenoxy)ethane (BTBPE), and 2 dechlorane plus isomers (DP, syn-DP and
      anti-DP)) varied from ND to 169,000 ng g-1 (mean +/- SD, 46,900 +/- 44,700 ng g
      1). BDE 209 and DBDPE were the dominant components and their concentration ranges
      were from ND to 106,000 ng g-1 and ND to 81,900 ng g-1, respectively. Generally,
      the HFR content and plastic variety closely correlate, and the ?HFR
      concentrations in the polyvinyl chloride (PVC, N = 5), polypropylene (PP, N = 9),
      acrylonitrile butadiene styrene (ABS, N = 5), polystyrene (PS, N = 1) and
      polyethylene (PE, N = 3) samples were 65,300 +/- 42,400, 36,700 +/- 56,000,
      30,000 +/- 25,200, 24,300 and 4330 +/- 7500 ng g-1, respectively. The HFR
      abundance in plastic from Guangdong (76,000 +/- 56,400 ng g-1, N = 7) and Hebei
      (37,500 +/- 11,500 ng g-1, N = 4) was much higher than that for other
      provinces/cities.

PMID- 30235596
TI  - Do thermal infrared (TIR) remote sensing and direct hyporheic measurements (DHM)
      similarly detect river-groundwater exchanges? Study along a 40 km-section of the
      Ain River (France).
AB  - Water exchanges through the hyporheic zone are crucial to many ecological
      processes in streams. One major challenge for river managers is to find a
      practical method for localizing these exchanges using rapid data acquisition
      techniques. This work compares spatially continuous data, acquired by Thermal
      Infrared (TIR) techniques, with discrete data collected in surface water and in
      the hyporheic zone (DHM), at sites of expected water exchanges (gravel bars).
      Forty gravel bars, distributed along a 40 km-sector of the Ain River were sampled
      at upstream- and downstream-bar positions (80 sites) in order to reveal hyporheic
      exchanges. At each site, 4 physico-chemical parameters were measured at 0, -20
      and -50 cm beneath the sediment surface. The field collections of TIR high
      resolution images were conducted concomitantly, at low flow and high surface
      water temperatures. Among the 80 sites selected for field measurements, 14 were
      identified as upwellings (groundwater inputs) and 66 as downwelling sites. From
      those 14 upwellings, 13 were also identified with TIR. The 44 additional sites
      identified with TIR corresponded to small-sized cold-water patches situated along
      the gravel bars or to groundwater discharge sites located between the bars (19
      lateral seeps). Nevertheless, the DHM method documented on downwelling exchanges
      (infiltration of surface water), which were not captured by TIR images, and may
      represent hyporheic hotspots especially for benthic invertebrates. Along the
      studied sector of the Ain River, these downwelling zones were much more numerous
      than upwelling ones. Both methods in combination provide a rather complete
      picture of water exchange along rivers and are needed to evaluate the potential
      as refuges zones during critical dry periods.

PMID- 30235597
TI  - Meteorological conditions, elevation and land cover as predictors for the
      distribution analysis of visceral leishmaniasis in Sinkiang province, Mainland
      China.
AB  - Visceral leishmaniasis (VL) is a fatal disease caused by sandfly-borne protozoa
      of the Leishmania genus. This study explored the influence of environmental
      factors on the distribution of VL in Sinkiang province, Mainland China, which is
      a known natural focus of leishmaniasis. Disease identification records were
      obtained from publicly available data, in which the existence of VL at each
      geographical location had been recorded as part of the surveillance of
      leishmaniasis in Sinkiang province. Maximum entropy modelling (Maxent) was used
      to predict the distribution of VL across Sinkiang province, and to match this
      distribution against environmental variables relating to elevation, climate and
      land cover, obtained from the WorldClim database, China Meteorological Data
      Sharing System and the National Geomatic Center of China dataset, respectively.
      Finally, a regional-scale map was developed to show the potential distribution of
      VL in the Sinkiang province. Receiver-Operating characteristic (ROC) analysis was
      used to evaluate the performance of the model. The daily average temperature,
      maximum temperature of the warmest quarter, daily precipitation and precipitation
      of the driest month were each found to be predictive of the distribution of VL in
      Sinkiang. Moreover, we found that presence of VL was significantly influenced by
      the distribution of grassland and shrubland. The results demonstrate that with
      proper construction and design, probability surfaces using Maxent can be used as
      an accurate method by which to predict the distribution of VL in Sinkiang
      province. The information generated by the model could be used to inform the
      design of detailed prevention and control strategies for leishmaniasis in this
      region of Mainland China.

PMID- 30235598
TI  - Impact of primary NO2 emissions at different urban sites exceeding the European
      NO2 standard limit.
AB  - A large part of the European population is still exposed to ambient nitrogen
      dioxide (NO2) levels exceeding the European Union (EU) air quality standards,
      being a key challenge to reduce NO2 concentrations across many European urban
      areas, particularly close to roads. In this work, a trend analysis of pollutants
      involved in NO2 processes was done for the period 2003-2014 in traffic sites from
      three Spanish cities (Barcelona, Madrid and Granada) that still exceed the
      European NO2 air quality standard limits. We also estimated the contributions of
      primary NO2 emissions and photo-chemically formed NO2 to the observed ambient NO2
      concentrations in order to explore their possible role in the observed NO2
      concentration trends. The NOx and NO concentrations at these traffic sites showed
      significant decreasing trends during the period 2003-2014, especially at
      Barcelona (BARTR) and Madrid (MADTR) traffic stations. The NO2 concentrations
      showed statistically significant downward trends at BARTR and MADTR and remained
      unchanged at Granada traffic station (GRATR) during the study period. Despite the
      significant decrease in NO2 concentrations in BCNTR and MADTR during the analysed
      period, the NO2 concentrations observed over these sites still above the annual
      NO2 standard limit of 40 MUg m-3 and, therefore, more efficient measures are
      still needed. Primary NO2 emissions significantly influence NO2 concentrations at
      the three analysed sites. However, as no drastic changes are expected in the
      after-exhaust treatment technology that can reduce primary NO2 emissions to zero
      in the near future, only a substantial reduction in NOx emissions will help to
      comply with the NO2 European air quality standards. Reduction of 78%, 56% and 16%
      on NOx emissions in Barcelona, Madrid and Granada were estimated to be necessary
      to comply with the NO2 annual limit of 40 MUg m-3.

PMID- 30235599
TI  - Challenges and opportunities in functional carbon nanotubes for membrane-based
      water treatment and desalination.
AB  - Environmental applications of carbon nanotubes (CNTs) have grabbed worldwide
      attentions due to their excellent adsorption capacities and promising physical,
      chemical and mechanical properties. The functionalization of CNTs, which involves
      chemical/physical modification of pristine CNTs with different types of
      functional groups, improves the capabilities of CNT for desalination and/or
      removals of waterborne contaminants. This paper intends to provide a
      comprehensive review of functional CNT materials (f-CNT) and their existing and
      potential applications in membrane-based water treatment and desalination
      processes, with focuses on critical evaluation of advances, knowledge gaps and
      future research directions. CNT nanocomposite membranes have been studied at
      bench scale to efficiently remove a variety of waterborne contaminants and salts,
      while future improvement is under way with development in CNT functionalization
      techniques. The CNT-based membrane applications are found to possess a variety of
      advantages, including improve water permeability, high selectivity and
      antifouling capability. However, their applications at full scale are still
      limited by their high cost. Finally, we highlight that f-CNT membranes with
      promising removal efficiencies for respective contaminants be considered for
      commercialization and to achieve holistic performance for the purpose of water
      treatment and desalination.

PMID- 30235600
TI  - Optimization and mechanism studies on cell disruption and phosphorus recovery
      from microalgae with magnesium modified hydrochar in assisted hydrothermal
      system.
AB  - Considering the phosphorus (P) reserve state and its value, recovery of P from
      microalgae has become a popular topic. In this study, an integrated system of a
      hydrothermal process for microalgae cell disruption to release P and magnesium
      modified hydrochar adsorption to capture P was set up. Emission scanning electron
      microscopy with Energy Dispersive X-ray spectroscopy and Three-Dimensional
      Excitation Emission matrix spectroscopy with parallel factor analysis were
      applied to evaluate the P release process from microalgae and found the optimal
      breaking-wall condition (P release 90.5%, hydrothermal digestion mixture of H2O2
      and NaOH at 348 K). Parallel factor analysis showed there was a close
      relationship between P and humic-like substance. Hydrochar loaded with magnesium
      exhibited a strong affinity for P, with maximum capacity 89.61 mg/g at 318 K. The
      P adsorption fitted pseudo-second-order kinetic and Langmuir models. X-ray
      photoelectron spectroscopy and Fourier transform infrared spectroscopy were
      applied to reveal the mechanism of hydrochar modification and adsorption. It
      showed that Mg is loaded on the surface of hydrochar by electrostatic attraction
      and electron transfer with the carboxylic acid. P absorption was reached through
      anion exchange.

PMID- 30235601
TI  - Benefits of integrated nutrient management on N2O and NO mitigations in water
      saving ground cover rice production systems.
AB  - To cope with challenges of food security and water scarcity in rice production,
      water-saving ground cover rice production systems (GCRPSs) are increasingly
      adopted in China and globally. Reduced soil moisture as well as increased soil
      aeration and temperature under GCRPSs may promote soil N transformations, and in
      turn give rise to environmental challenges. These include emissions of the potent
      greenhouse gas nitrous oxide (N2O) and atmospheric pollutant nitric oxide (NO).
      Using conventional flooding rice cultivation as a reference, a three-year field
      experiment was conducted to investigate the performances of GCRPSs under
      inorganic (urea) or integrated nutrient management (a combination of synthetic
      and organic fertilizers), with regards to soil N2O and NO emissions as well as
      grain yields. N2O and NO emissions in GCRPSs exhibited high seasonal and
      interannual variations along with changes in soil inorganic N content and
      rainfall. When urea alone was applied, the average N2O and NO emissions from
      GCRPSs were 4.11 and 0.14 kg N ha-1, respectively. These emissions were
      significantly higher than those of conventional rice cultivation, with 1.47 and
      0.052 kg N ha-1 for N2O and NO, respectively. When integrated nutrient management
      was performed for GCRPSs, N2O and NO emissions were reduced by approximately 77%
      and 50%, respectively, i.e., the emission magnitude comparable with N-trace gas
      losses from conventional rice cultivation. Moreover, GCRPSs with integrated
      nutrient management resulted in optimal grain yields, and thus, the yield-scaled
      N2O + NO emissions were the lowest compared to other treatments. Averaged over 3
      years, the direct emission factors of N2O and NO for GCRPSs with urea alone were
      2.58% and 0.064%, respectively. Those for GCRPSs with integrated nutrient
      management were 0.48% and 0.016%, respectively. The results of this study suggest
      that GCRPS with integrated nutrient management is an eco-friendly strategy for
      optimizing crop yields while mitigating N2O and NO emissions.

PMID- 30235602
TI  - Spatio-temporal variations of atmospheric and soil polybrominated diphenyl ethers
      (PBDEs) in highly industrialized region of Dilovasi.
AB  - Polybrominated diphenyl ethers (PBDEs) were investigated in ambient air of a
      highly industrialized region at 23 different sampling sites for 12 months. Total
      concentrations of 8 PBDE congeners (Sigma8PBDE) were found to be between 5.73 and
      520 pg m-3 (94.7 +/- 78.9; average +/- SD) and BDE-209 was the predominant
      congener, followed by BDE-47 and/or BDE-99. Their contributions to Sigma8PBDE
      were 71 +/- 13, 9 +/- 4% and 8 +/- 4%; respectively. Compared to previous studies
      around the world, high concentrations detected in Dilovasi demonstrated the
      severity of atmospheric PBDE pollution in the area. For all sampling sites,
      average PBDE concentration obtained in summer (118.5 +/- 98.7 pg m-3) was higher
      than one found in winter period (79.7 +/- 59.1 pg m-3) and this seasonal
      difference was more obvious in industrial/urban sites (p < 0.05), probably due to
      enhanced volatilization from ongoing PBDE sources such as waste incineration and
      iron-steel plants. The soil-air exchange tendencies of PBDEs did not show
      substantial differences between the sampling periods with small variations for
      each congener. All congeners either tend to deposit to soil or to be within the
      equilibrium range for all seasons. This reflects the impact of local ongoing
      sources rather than temperature on the direction of soil-air exchange of PBDEs in
      this region. Specific congener ratios such as BDE-47/-99 and -99/-100 confirmed
      the impact of local sources rather than long-range transport on PBDE congeners in
      the study area. According to the Positive Matrix Factorization (PMF) results, the
      BDE-209 content of the first factor was found to be 91.7% and this factor was
      attributed to the deca-BDE technical formulations. The second factor was highly
      rich with both BDE-183 (%61) and BDE-28 (%52) and identified as octa-BDE
      technical products. The last factor was highly loaded with BDE-99, BDE-47, BDE
      100, BDE-154 and BDE-153 and has been determined as the penta-BDE commercial
      formulations.

PMID- 30235604
TI  - Nano/micron particles released from newspapers under different reading
      conditions.
AB  - Despite the extensive use of the Internet, printed newspapers remain a primary
      information source. In this study, reading a newspaper in a relatively confined
      or poorly ventilated indoor space was simulated to determine the profile of
      particles released from the newspaper into the air. The consecutive simulated
      conditions were reading without agitation of the newspaper (NoAg), followed by
      reading with agitation of the newspaper (Ag) and post-reading absent the
      newspaper (PostR), repeated with four newspapers. We found that particle number
      concentration (SigmaN) fell during Ag owing to electroadhesion of ultrafine
      particles (<200 nm) caused by static charges created by friction between the
      paper surface and the air as a result of newspaper agitation. Conversely,
      particle surface area concentrations (SigmaA) and particle volume concentrations
      (SigmaV) increased significantly during Ag. This was because the larger, fine (1
      2.5 MUm) and coarse mode (2.5-10 MUm), particles were detached from the newspaper
      during agitation due to inertial detachment - the release of even a small number
      of these particles contributing greatly to SigmaA and SigmaV. The critical
      particle number diameter (CPND) occurred at 207-310 nm. Particles smaller than
      this were subject to electroadhesion during Ag. The critical particle volume
      diameter (CPVD) occurred at 130-497 nm. Particles larger than this were subject
      to inertial detachment during Ag. These observations indicate that the
      electroadhesion of smaller particles and the inertial detachment of larger
      particles occur simultaneously. Particle mass concentrations were found to be as
      high as 168.7-534.3 MUg m-3. However, these findings of high potential
      concentrations were based on the measurement in relative small micro-environment.
      The inhalation of such concentrations is a health risk for people who regularly
      read newspapers in a relatively confined or poorly ventilated indoor space.

PMID- 30235603
TI  - The interplay between natural organic matter and bromide on bromine substitution.
AB  - This study examined the interplay between bromide and DOM characteristics,
      described with SUVA254, in terms of formation and speciation of selected DBPs
      [trihalomethanes (THMs), haloacetic acids (HAAs), and haloacetonitriles (HANs)]
      during chlorination under various water treatment conditions. Cytotoxicity
      evaluations were also conducted based on the types and amounts of DBPs formed and
      their corresponding cytotoxicity index values. The results showed that the
      formation of THMs and HAAs increased as the specific UV absorbance at 254 nm
      (SUVA254) of the waters increased; however, there was no clear trend for HANs.
      THM and HAN formation increased with increasing bromide levels, while there was
      no bromide effect on the HAA formation. Lower HAA5 (monochloroaceticacid,
      monobromoaceticacid, dichloroaceticacid, trichloroaceticacid, dibromoaceticacid)
      to HAA9 (monochloroaceticacid, monobromoaceticacid, dichloroaceticacid,
      trichloroaceticacid, dibromoaceticacid, bromochloroaceticacid,
      bromodichloroaceticacid, dibromochloroaceticacid, tribromoaceticacid) ratios,
      independent of SUVA254, were observed with increasing bromide levels. Bromine
      substitution factor (BSF) values were in the order of BSFDHAN > BSFTHAA > BSFTHM
      ~ BSFDHAA. BSF values for all class of DBPs decreased with increasing SUVA254.
      TOX formation increased with increasing SUVA254 without an impact of bromide
      concentration. UTOX/TOX ratios were higher in treated low SUVA254 waters than raw
      waters having higher SUVA254 values, and they decreased with increasing initial
      bromide concentration in all sources. Increasing bromide concentration from 0.5
      MUM to 10 MUM elevated the calculated cytotoxicity index values of waters.
      Despite their much lower (approximately ~10 times) formation as compared to THMs
      and HAAs, HANs controlled the calculated cytotoxicity of studied waters.

PMID- 30235605
TI  - Microbial reduction of nitrate in the presence of zero-valent iron.
AB  - Microbial reduction of nitrate in the presence of zero-valent iron (ZVI) was
      evaluated in anoxic shake flasks to assess the feasibility of ZVI-facilitated
      biological nitrate removal. Nitrate was completely reduced within 3days in the
      presence of both ZVI and microorganisms (ZVI-M). In contrast, only 75% of the
      nitrate was reduced in the presence of ZVI but without microbial inoculum.
      Nitrate removal was affected by ZVI-M flasks initial pH, nitrate concentration
      and ZVI dosage. Nitrate removal in the inoculated ZVI flasks system could be
      divided into two phases: adaptation phase and log phase which could be described
      by first-order kinetic equations. The analysis of bacterial communities in the
      inoculated flasks in the absence and presence of ZVI, indicated that the addition
      of ZVI increased the relative abundance of Methylotenera spp., Alcaligenes
      eutrophus, Pseudomonas spp. which might play an important role in nitrogen
      removal. The presence of ZVI could enhance biological denitrification through
      four mechanisms: the biological reduction of nitrate with 1) electrons derived
      directly from ZVI; 2) with hydrogen released from ZVI; 3) with Fe2+ released from
      ZVI; and 4) with acetate generated by homoacetogens which utilize H2 released
      from ZVI.

PMID- 30235606
TI  - Impact of industrial wastewater on the dynamics of antibiotic resistance genes in
      a full-scale urban wastewater treatment plant.
AB  - Urban Wastewater Treatment Plants (UWTPs) treating mixed urban sewage and
      industrial wastewater are among the major hotspots for the spread of Antibiotic
      Resistance Genes (ARGs) into the environment. This study addresses the impact of
      the wastewater origin on ARG dynamics in a full-scale UWTP (15,000 Population
      Equivalent, PE) by operating the plant with and without industrial wastewater.
      Composite samples (4 L) from different treatment points were characterized for
      their chemical composition, bacterial abundance and for the abundance of four
      resistance genes against tetracycline, sulfonamides, erythromycin, and quinolones
      (tetA, sul2, ermB, and qnrS), and of the class 1 integrons (intI1). Although the
      chemical composition of the outflow significantly differed when the plant
      operated with or without industrial wastewater, the system efficiency in the
      removal of bacterial cells, ARGs, and intI1 was constant. The final disinfection
      by peracetic acid (PAA) did not affect the removal of ARGs, independently of the
      wastewater origin and the chemical characteristics of the inflows. Our results
      demonstrated that a well-functioning small size UWTP could treat a significant
      amount of industrial wastewater mixed in the urban sewage without affecting the
      overall ARGs and class 1 integrons released into the environment.

PMID- 30235607
TI  - Effects of mixed surfactants on the bioaccumulation of polycyclic aromatic
      hydrocarbons (PAHs) in crops and the bioremediation of contaminated farmlands.
AB  - Given the widespread contamination of polycyclic aromatic hydrocarbons (PAHs) in
      farmland, it is necessary to develop a technology to ensure the safety of
      agricultural productions and remediate the contaminated soils. In this study, a
      series of mixed surfactants were utilized to reduce the uptake of PAHs by crops
      in farming period and enhance the plant-microbe associated biodegradation in
      fallow period. During the farming period, the mixtures of cetyltrimethyl ammonium
      bromide (CTMAB) and Tween 80 were attached on soil by cationic-exchange and
      hydrogen bond, respectively, which increased soil organic matter to partition the
      bio-available fraction of PAHs. The maximum reduction of phenanthrene and pyrene
      was 88.6% and 94.9% for chrysanthemum (Chrysanthemum coronarium L.), and 90.6%
      and 91.9% for raphanus (Raphanus sativus L.), respectively. During the fallow
      period, sodium dodecyl benzene sulfonate (SDBS) reduced the adsorption loss of
      Tween 80 on soil to enhance desorption of PAHs. The mixtures of SDBS and Tween 80
      increased the water-soluble fraction of PAHs in soils, modified bacterial
      community structure, and enriched the functional genes involved cell motility and
      signal transduction. Removal efficiencies of phenanthrene and pyrene in soils
      were high to 86.7% and 90.7%. This systematic technology provided an effective
      solution to remediate and plant on PAH-contaminated farmlands.

PMID- 30235609
TI  - Removal of emerging contaminants from wastewater through pilot plants using
      intermittent sand/coke filters for its subsequent reuse.
AB  - Effluents from wastewater treatment plants (WWTPs) are widely recognized as the
      main source of emerging contaminants (stimulants and antibiotics). In this study,
      intermittent sand and/or coke filters were installed as a tertiary treatment at
      the outlet of a secondary settling tank at the WWTP in Medina Sidonia, Spain.
      Regular sampling followed by solid-phase extraction (SPE) and analysis by liquid
      chromatography-mass spectrometry (UPLC-MS) showed the complete removal of the
      concentrations of the emerging contaminants (caffeine, theobromine, theophylline,
      amoxicillin and penicillin G). Moreover, optimal filtration conditions for the
      reuse of treated water were presented.

PMID- 30235608
TI  - Linking hydrological and bioecological benefits of green infrastructures across
      spatial scales - A literature review.
AB  - Green infrastructure (GI) mitigates the negative effects of urbanization and
      provides hydrological and bioecological benefits. However, these benefits are
      highly scale-dependent because the processes involved vary at different spatial
      scales; there are thus additional challenges in GI planning when multiple
      benefits are targeted. Therefore, it is necessary to review and summarize the
      theoretical understandings and practical experience obtained from previous
      studies and projects related to the hydrological and bioecological benefits of GI
      practices. In this review, we elaborate the conceptual linkages between the
      hydrological and bioecological benefits of GI practices across different scales.
      Smaller-scale benefits lay the foundation for larger-scale benefits. Hydrological
      benefits drive bioecological benefits by providing consistent water flows and
      maintaining a suitable soil environment. Bioecological benefits in turn enhance
      hydrological benefits by increasing water uptake and filtration via more active
      biological processes. We next summarize the study area sizes of existing studies
      and categorize them according to their study approaches and targeted benefits.
      The study area sizes in studies that make use of laboratory experiments,
      numerical modeling, and remote sensing have increased in recent years and vary
      greatly between each type of study; the study area size in studies of
      bioecological benefits was larger than in studies of hydrological and water
      quality benefits. However, there is a research gap in studies of bioecological
      benefits at the catchment scale. Furthermore, we summarize the major research
      topics and findings of bioecological benefits of GI practices at different
      spatial scales. We conclude this review with recommendations for future research,
      which include performing more studies at the catchment scale, developing hydro
      bioecological statistical relationships to simplify the quantification of
      bioecological benefits, and developing databases to document the bioecological
      benefits of GI practices.

PMID- 30235610
TI  - Dual wave farms and coastline dynamics: The role of inter-device spacing.
AB  - In dual wave farms, i.e., arrays of wave energy converters (WECs) with a dual
      function - generation of renewable power and mitigation of coastal erosion - the
      spacing between the WECs is a fundamental design parameter. The present research
      has the objective of establishing how this parameter affects the shoreline
      evolution behind the array and, on this basis, to propose and apply a method to
      determine the optimum spacing for coastal protection. The method is demonstrated
      on a beach subjected to severe erosion. Five case studies are considered: four
      with different inter-WEC spacings, and one without the wave farm (baseline). A
      spectral wave propagation model is applied to analyse the variations in
      significant wave height behind the WEC array. Longshore sediment transport rates
      are calculated, and a shoreline model is applied. We find that in all the case
      studies the dry beach area is greater than in the baseline (no farm) case study,
      which proves the capacity of the dual WEC array to mitigate the erosive trends of
      the system. Importantly, we obtain that the inter-WEC spacing plays a fundamental
      role in the evolution of the shoreline and, consequently, in the effectiveness of
      the WEC array for coastal protection. The case studies with intermediate spacings
      yield the best performance in terms of dry beach area. More generally, the
      benefits of dual wave farms in terms of protection of coastal properties and
      infrastructure, and the ensuing savings in conventional coastal defence measures
      (coastal structures, beach nourishment, etc.) contribute to the development of
      wave energy by enhancing its economic viability. The methodology presented in
      this paper can be used to optimize the design of dual wave farms elsewhere.

PMID- 30235611
TI  - Quantifying atmospheric N deposition in dryland ecosystems: A test of the
      Integrated Total Nitrogen Input (ITNI) method.
AB  - Estimating nitrogen (N) deposition to terrestrial ecosystems is complicated by
      the multiple forms and routes of N loading from the atmosphere. We used the
      integrated total nitrogen input (ITNI) method, which is based on the principle of
      isotope dilution within a plant-liquid-sand system, to quantify N inputs to
      coastal sage scrub ecosystems in Riverside, California. Using the ITNI method, we
      measured atmospheric N deposition of 29.3 kg N ha-1 yr-1 over a range of
      aboveground plant biomass of 228 to 424 g m-2. From 85 to 96% of the atmospheric
      N inputs were taken up by plants in the ITNI modules with most of the
      assimilation mediated by, and stored in, aboveground biomass. Parallel
      measurements using conventional approaches yielded deposition rates of 25.2 kg N
      ha-1 yr-1 when using the inferential method and 4.8 kg N ha-1 yr-1 using
      throughfall collectors. The relatively low throughfall estimates were attributed
      to canopy retention of inorganic N, low rainfall, and to the fact that the
      throughfall flux data did not include organic N and stomatal uptake of N gases.
      Also, during dry periods, frequent watering of ITNI modules may have increased
      stomatal conductance and led to overestimates of N deposition. Across published
      studies that used the ITNI method, areal N deposition rates varied by ~40-fold,
      were positively correlated with plant biomass and 90% of the variability in
      measured deposition rates can be explained by plant biomass production. The ITNI
      method offers a holistic approach to measuring atmospheric N deposition in arid
      ecosystems, although more study is needed to understand how watering rates effect
      N deposition measurements.

PMID- 30235612
TI  - Quantification of subsurface hydrologic connectivity in four headwater catchments
      using graph theory.
AB  - Hillslope-stream connectivity significantly affects streamflow and water quality
      responses during rainfall and snowmelt events, but is difficult to quantify. One
      approach to quantify subsurface hillslope-stream connectivity is graph theory,
      which considers linear connections between groundwater measurement sites. We
      quantified subsurface connectivity based on surface topography and shallow
      groundwater data from four small (<14 ha) headwater catchments in the Italian
      Dolomites and the Swiss pre-Alps, determined the relation between rainfall,
      antecedent wetness conditions and subsurface connectivity and assessed the
      sensitivity of the results to changes in the measurement network. Event total
      stormflow was correlated to maximum subsurface connectivity. Subsurface
      connectivity increased during rainfall events but maximum connectivity occurred
      later than peak streamflow, resulting in anti-clockwise hysteretic relations
      between the two. Subsurface connectivity was positively correlated to rainfall
      amount. Maximum subsurface connectivity was related to the sum of total rainfall
      plus antecedent rainfall for the Dolomitic catchments, but these relations were
      less clear for the pre-alpine catchments. For the pre-alpine catchments, the
      fractions of time that the groundwater monitoring sites were connected to the
      stream were significantly correlated to the upslope site characteristics, such as
      the Topographic Wetness Index. For the Dolomitic catchments, the fractions of
      time that the monitoring sites were connected to the stream were correlated to
      the topographic characteristics of the upslope contributing area for the
      catchment with the small riparian zone, and with the distance to the nearest
      stream for the catchment with the large riparian zone. The leave-one-out
      sensitivity analysis showed that small changes in the structure of the
      groundwater monitoring networks had a limited influence on the results,
      suggesting that graph-theory approaches can be used to describe subsurface
      hydrologic connectivity. However, the proposed graph-theory approach should be
      verified in other catchments with different groundwater monitoring networks.

PMID- 30235613
TI  - Performance and mechanisms of emerging animal-derived biochars for immobilization
      of heavy metals.
AB  - Animal-derived biochars (ADBs) are a series of newly emerging biochars from the
      pyrolysis of animal carcasses. Their elemental composition and structural
      properties would be quite different to those of plant-based biochars and/or
      manure-derived biochars (MDBs). In this work, ADBs derived from cattle and swine
      carcasses were applied to investigate their sorption potentials and mechanisms
      for immobilization of Pb(II), Cd(II), Cu(II), and Hg(II). ADBs showed high
      calcium (Ca; >27%) and phosphorus (P; >15%) contents and relatively low carbon
      (C; <8%) content. Ca and P were present in the skeleton as calcium-phosphate
      complexes, dominantly as hydroxyapatite (HAP), which was identified by CP-MAS 31P
      NMR analysis. By contrast, the reference biochars derived from cattle, swine, and
      poultry manures possessed low Ca (<13%) and P (<4%) contents and relatively high
      C (>30%) content. Sorption experiments showed that ADBs were more effective in
      immobilizing Pb(II), Cd(II), and Cu(II) than MDBs. However, the affinities of
      ADBs for Hg(II) were lower than those of MDBs. Characterization analyses
      indicated that Pb(II) was effectively immobilized via precipitation, whereas ion
      exchange was the dominant mechanism in combining Cd(II) or Cu(II) with ADBs. ADBs
      are unsuitable for immobilizing Hg(II) because of the lack of oxygen-containing
      functional groups on the C surface, which can induce the reduction of Hg(II) to
      form Hg2Cl2. The immobilized heavy metals were difficult to be rereleased from
      ADBs in simulated acid rain environment. Hence, ADBs are promising biochars for
      immobilizing Pb(II), Cd(II), and Cu(II).

PMID- 30235614
TI  - qnrD-harboring plasmids in Providencia spp. recovered from food and environmental
      Brazilian sources.
AB  - QnrD is a plasmid-mediated quinolone resistance (PMQR) determinant first reported
      in clinical Salmonella enterica isolates from China, located on nonconjugative
      plasmids of 4270 bp. Since then, the qnrD gene has been mostly found on plasmids
      around 2683 bp in Proteus and Morganella genera. However, Providencia spp.
      strains carrying qnrD-harboring plasmids have only been reported among clinical
      samples, in France and China. In this paper we describe two plasmids carrying
      qnrD in Providencia spp. isolated from Brazilian food and coastal waters. These
      plasmids present high coverage and identity with those recovered in France. Our
      results emphasize the relevance of the Proteeae tribe as reservoirs of qnrD and
      include P. rettgeri as a possible environmental carrier of this gene.

PMID- 30235615
TI  - Selective effect and elimination of antibiotics in membrane bioreactor of urban
      wastewater treatment plant.
AB  - Analyzing the temporal dynamics of antibiotics, antibiotic resistance genes
      (ARGs) and the functional community could contribute to the regulation and
      optimization of wastewater treatment plant (WWTP) operation to achieve better
      antibiotics and ARGs removal performances during different seasons. However,
      there is little research in this area. Therefore, in this study, samples were
      collected from the influent, activated sludge (AS), and permeate of the membrane
      bioreactor (MBR) in a WWTP located in Beijing, China, biweekly over 13 months,
      and then analyzed systematically. The removal efficiency for all detected
      antibiotics through biodegradation and adsorption was 59.25 +/- 2.79%, with the
      highest rate of 64.79 +/- 4.68% observed in summer, indicating that the higher
      temperature in summer may promote biodegradation in MBR. In contrast, the
      elimination of antibiotics through microfiltration was negligible and
      unfavorable, with negative overall removal rates. However, a positive rejection
      rate of 9.48 +/- 8.92% was only observed in winter, indicating that a colder
      temperature might lead to better, but still limited, antibiotics rejection.
      Sulfonamides (SAs) were more likely to impose a selective pressure on their
      corresponding ARGs. However, due to the degradability of tetracyclines (TCs) and
      potential selection of ARGs in wastewater before entering WWTP, there were still
      TC resistances with non-detectable TCs. Significantly negative relationships were
      observed between the relative abundance of nitrifying bacteria (Nitrosomonas and
      Nitrospira) and the concentrations of certain antibiotic classes, indicating that
      nitrifying bacteria could be involved in the co-metabolic biodegradation of
      certain antibiotics through enzyme catalyzation during nitrification.

PMID- 30235616
TI  - The effects of recreational and commercial navigation on fish assemblages in
      large rivers.
AB  - Recreational and commercial navigation is omnipresent, rendering European large
      rivers highways for cargo vessels, passenger ships and sport boats. Any types of
      motorized vessels create waves and drawdown eroding shallow shore areas.
      Consequently, inland navigation alters the living environment of fish with
      specific habitat requirements on nursing, hatching and spawning along shorelines.
      We assess the influence of recreational (sport boats) and commercial navigation
      (passenger ships, cargo vessels) on fish assemblages. Seven fish population
      metrics (FPM) were analyzed for 396 fish samplings at 88 sites in six large
      rivers characterized by seven different estimates of navigation intensity to
      identify FPM sensitive to inland navigation. Navigation intensity was
      characterized by frequency, total freight transported, total carrying capacity,
      degree of capacity utilization and by numbers of empty running vessels, aiming to
      approximate whether frequency, freight or draft of cargo vessels matter most.
      Densities of lithophilic fish were most sensitive to frequencies of sport boats,
      passenger ships and cargo vessels and declined as navigation traffic increased.
      Densities of rheophilic fish declined likewise but were less sensitive than
      lithophils. Frequency, freight and carrying capacity of cargo vessels had
      comparable effects on FPM and are equally useful in addition to frequency of
      sport boats and passenger ships to assess the impacts of recreational and
      commercial navigation on fish assemblages. Lower species richness indicated a
      specific influence of vessel draft on fish diversity. Our study shows that both
      recreational and commercial navigation impair fish assemblages in navigable
      rivers. Operation-related navigation impacts act on top of river regulation and
      engineering works to maintain fairways in the main channel. Therefore, impacts
      from recreational and commercial navigation must be especially addressed in
      addition to mitigating impacts from river regulation and hydromorphological
      degradation to achieve environmental objectives such as species conservation,
      ecological improvements and river rehabilitation.

PMID- 30235617
TI  - Wetland areas' direct contributions to residents' well-being entitle them to high
      cultural ecosystem values.
AB  - Wetlands in urban areas will be crucial to counteract the effects of climate
      change, for example, by improving flood protection and regulating local climate.
      To gain acceptance for larger-scale creation of wetlands, total values must be
      identified and revealed. Provisioning and regulating ecosystem services can be
      described as the quantitative effect, but cultural ecosystem services require
      other assessments. This study sought to determine whether peri-urban and urban
      wetland areas contribute to the well-being and quality of life of nearby
      residents, and to capture their value relative to two other types of green areas
      (i.e., parks and urban forests). A postal questionnaire survey, based on
      validated environmental psychology instruments, was distributed to residents in
      three municipalities with wetland areas of different structures and locations. In
      these municipalities, respondents (n = 474; response rate = 40%) reported that
      the wetland area contributed to several quality-of-life aspects, such as
      encountering nature and experiencing beauty. The areas also facilitated
      activities that support well-being, were perceived to have high restorative
      qualities, and evoked positive affective responses. All wetland areas were rated
      high on most of the measured concepts, but their value relative to other green
      areas differed possibly depending on the accessibility of the wetland and the
      availability of other green areas. The location and extent to which the wetland
      area was integrated in the residential area determined what quality-of-life
      aspects were most satisfied. Wetland areas can be ascribed cultural ecosystem
      service values based on how residents perceive their contribution to their
      quality of life. These values can be added to those of provisioning and
      regulating ecosystem services, forming the basis for planning urban environments.

PMID- 30235618
TI  - Assessing the drought mitigation ability of the reservoir in the downstream of
      the Yellow River.
AB  - Due to climate change and human activities, drought frequency and its
      corresponding impact have intensified in many regions across China. Reservoirs
      are key in regulating streamflow and mitigating a drought's impact. Therefore, it
      is vital to analyze their drought mitigation ability. In this study, the drought
      adaptation capacity and drought resistance capacity of the reservoir are selected
      as two drought mitigation ability metrics to measure the effectiveness of a
      reservoir when facing a drought. The drought adaptation capacity represents the
      ability of a reservoir to prevent and mitigate damage caused by drought. It is
      assessed from two viewpoints, one reflecting the reservoir scale and layout
      reasonability, while the second reflecting the engineering operation and
      management. The drought resistance capacity refers to the ability of a reservoir
      to meet the water demand under a certain level of a drought (i.e. drought joint
      return period, which is defined later), and is calculated based on the
      reservoir's water supply and water demand. These two drought mitigation ability
      metrics can be applied not only for a single reservoir, but also for a group of
      reservoirs. This study applies these two metrics in the downstream of the Yellow
      River for a group of reservoirs. The results show that: 1) the ability of
      reservoirs in the downstream of the Yellow River for prevention and mitigation of
      damage caused by drought rates in the normal grade; and 2) the reservoirs can
      better resist the drought whose joint return period is smaller than 2 years while
      the drought resistance capacity is weak when the joint return period is over 6
      years. Overall, the basin's drought adaptation and resistance capacity need to be
      improved. Management and operation of current water conservancy projects still
      need to be enhanced.

PMID- 30235619
TI  - Improved simulation-optimization approach for identifying critical and
      developable pollution source regions and critical migration processes for
      pollutant load allocation.
AB  - Simulation-optimization approaches are widely used in land-based pollutant load
      allocation and management. However, existing simulation-optimization approaches
      do not optimize the entire pathway of pollution (i.e., generation,
      transportation, and emission). Thus, the selected allocated load scheme and its
      reduction management are incomplete and non-optimal in supporting effective
      reduction measures to set in further. This study aims to establish a simulation
      optimization load allocation approach covering the entire pathway of pollution
      and construct separate allocated loads for each migration process. By comparing
      the allocated loads to the actual pollutant loads, the critical and developable
      pollution source regions (CPSRs and DPSRs) and the critical pollution migration
      processes (CPMPs) are identified, and specific pollution management indicators
      are established for each pollution source region. This approach is applied to the
      Bohai Rim, which is currently a major economic development center with a most
      seriously deteriorating sea area in China. The CPSRs, DPSRs, and CPMPs for total
      nitrogen are identified, and comparisons of the management indicators with
      existing approaches are made. Water quality under the allocated load emissions is
      simulated via a simulation water quality model and compared with that of the
      actual pollutant loads. Quantitative results indicate that the new approach
      combines the specific mitigation indicators for each CPSR and CPMP when allowing
      the extra generation of allocated loads for DPRSs while keeping the water quality
      of the Bohai Sea under control.

PMID- 30235620
TI  - Building global change resilience: Concrete has the potential to ameliorate the
      negative effects of climate-driven ocean change on a newly-settled calcifying
      invertebrate.
AB  - Global climate change is driving sea level rise and increasingly frequent storm
      events, which are negatively impacting rapidly-growing coastal communities. To
      mitigate these impacts, coastal infrastructure must be further protected by
      upgrading hard defences. We propose that incorporating pH-buffering materials
      into these upgrades could safeguard marine organisms from the adverse effects of
      ocean acidification and ocean warming during the vulnerable transition from
      planktonic larvae to benthic juveniles. To test this, we examined the effects of
      ocean warming (24 or 27  degrees C), ocean acidification (pH 8.1, 7.9, 7.7), and
      substratum (concrete, greywacke, granite) in all combinations on the settlement
      success of an ecologically and commercially important sea urchin, Tripneustes
      gratilla. Low pH (7.9, 7.7) generally reduced the quantity and size of juveniles
      four weeks post-settlement, although this was partially ameliorated by increased
      temperature (24 vs. 27  degrees C). In the warmed and acidified treatments,
      settlement rates were lower on concrete than granite or greywacke, but two weeks
      post-settlement, juveniles on concrete were larger, and had longer spines and
      higher survival rates than on greywacke or granite, respectively. The benefits
      provided by concrete to newly-settled juveniles may be related to alkali
      chemicals leaching from concrete buffering low pH conditions in surrounding
      seawater and/or increased availability of bicarbonate in the boundary layers
      around its surface. Our results highlight the potential for pH-buffering
      materials to assist marine organisms in coping with the effects of changing ocean
      conditions, but further research is required to understand the generality and
      mechanism(s) driving the beneficial effects of concrete and to test pH-buffering
      materials in the field.

PMID- 30235621
TI  - Bird population changes reconstructed from isotopic signals of peat developed in
      a nutrient enriched tundra.
AB  - Five peat sequences were studied to identify the time the little auk Alle alle
      colonies originated in the Hornsund area (Spitsbergen). Elemental and stable
      isotope analysis of nitrogen and carbon was applied as markers for bird activity.
      The peat sequences were dated with 210Pb and radiocarbon methods. The results
      showed that peat development related to seabird activity is significantly older
      (at least 300 years old) in localities closer to the fjord's mouth (west) than
      those located deeper in the fjord (east), which are ~100 years old. Isotopic
      signals indicated that bird activity in the western localities decreased
      simultaneously with the growth of the eastern colonies. Colonization by birds of
      new localities correlated with the termination of the Little Ice Age and the
      meaningful decrease in the glacier area of the region. Hence, we suggest that the
      availability of new localities for nesting in talus cones, nival moraines and
      lateral moraines on gentle mountain slopes with south-eastern exposition
      attracted the little auk due to better thermal conditions, isolation from strong
      westerly winds and better protection from predation by gull Larus hyperboreus.
      The expansion of little auks to the new localities was fast (20-30 yrs), and
      there are no records of changes in bird impacts on the tundra environment after
      1920.

PMID- 30235622
TI  - Chemical oxidants affect byssus adhesion in the highly invasive fouling mussel
      Limnoperna fortunei.
AB  - Biofouling by the invasive mussel species Limnoperna fortunei has caused severe
      negative consequences in various freshwater ecosystems, but there is still a lack
      of effective antifouling strategies for this species, particularly in drinking
      water treatment systems where many existing strategies cannot be used. Chemical
      oxidants have been proposed to potentially control fouling mussels by influencing
      3,4-dihydroxyphenylalanine oxidation involved in byssus adhesion. To test this
      potential control strategy, L. fortunei adults were exposed to four oxidants:
      sodium hypochlorite (NaClO), potassium permanganate (KMnO4), hydrogen peroxide
      (H2O2) and chloramine T (CAT) at concentrations of 0.5, 1.0, 3.0 and 5.0 mg L-1
      for one week. The results showed that low concentrations of KMnO4 stimulated foot
      protein secretion, which was beneficial to byssus production (number and length).
      NaClO and H2O2, but not KMnO4 and CAT, significantly inhibited byssus production
      and reduced breaking force, causing an increased byssus shedding rate. However,
      only NaClO dissolved byssus and altered the failure location from the byssal
      thread to adhesive plaque, even when exposed at low concentrations, showing its
      great impacts on byssus adhesion. Further analysis of polyphenoloxidase
      activities and gene expression profiles of LfBP-1, LfFP-2 and LfBP-3 revealed
      that chemical oxidants affected byssus adhesion by altering Dopa oxidation and
      foot protein gene expressions. This study, therefore, suggests that a low
      concentration of NaClO can be used as an alternative and environmentally friendly
      chemical for controlling L. fortunei biofouling by weakening byssus adhesion.

PMID- 30235623
TI  - The inhibitory impacts of nano-graphene oxide on methane production from waste
      activated sludge in anaerobic digestion.
AB  - The wide application of graphene oxide nanoparticles inevitably leads to their
      discharge into wastewater treatment plants and combination with the activated
      sludge. However, to date, it is largely unknown if the nano-graphene oxide (NGO)
      has potential impacts on the anaerobic digestion of waste activated sludge (WAS).
      Therefore, this work aims to fill the knowledge gap through comprehensively
      investigating the effects of NGO on carbon transformation and methane production
      in the anaerobic digestion of WAS. Biochemical methane potential tests
      demonstrated the methane production dropped with increasing NGO additions, the
      cumulative methane production decreasing by 7.6% and 12.6% at the NGO dosing
      rates of 0.054 mg/mg-VS and 0.108 mg/mg-VS, respectively. Model-based analysis
      indicated NGO significantly reduced biochemical methane potential, with the
      highest biochemical methane potential decrease being approximately 10% at the
      highest NGO dosing rate. Further experimental analysis suggested that the
      decreased methane production was firstly related to a decrease in soluble organic
      substrates availability during the process of sludge disintegration, potentially
      attributing to the strong absorption of organic substrates by NGO. Secondly, NGO
      significantly inhibited the methanogenesis by negatively affecting the
      corresponding enzyme activity (i.e. coenzyme F420), which could also resulted in
      a decreased methane production.

PMID- 30235624
TI  - The occurrence, distribution and degradation of antibiotics by ionizing
      radiation: An overview.
AB  - Antibiotics have been extensively applied, making them ubiquitous in aquatic
      environment. As emerging contaminants, the occurrence and distribution of
      antibiotics in the environment has received increasing attention due to their
      potential adverse effects on human health and ecosystem. However, antibiotics
      cannot be effectively removed in conventional biological treatment processes, and
      their natural biodegradation is also ineffective. In this review, the occurrence
      and distribution of antibiotics in aquatic environments, including surface water,
      wastewater and effluent of wastewater treatment plants, were analyzed and
      summarized. Recent progress of antibiotics degradation by ionizing radiation was
      reviewed. The various influencing factors, such as absorbed dose, initial
      concentration, inorganic anions and organic matters, on the removal efficiency of
      antibiotics were introduced and discussed. To improve their removal efficiency,
      several advanced oxidation processes (AOPs) such as H2O2, Fe2+, Fe2+/H2O2, as
      well as biological treatment processes, are combined with ionizing radiation.
      Some suggestions for future studies of antibiotics degradation by ionizing
      radiation were proposed. Ionizing radiation may be a promising technology for
      removal of antibiotics from water and wastewater.

PMID- 30235625
TI  - A review on novel composites of MWCNTs mediated semiconducting materials as
      photocatalysts in water treatment.
AB  - Many technologies were explored to eliminate the harmful pollutants entering
      water systems and to minimize their impact on environment. In general, photo
      catalysis is one of the sustainable techniques with wider applications and
      semiconductors in particular were efficiently utilized in the photocatalytic
      degradation of pollutants. Semiconducting materials, such as TiO2, ZnO, BiO, CdS,
      and Ag3PO4 are frequently used as photo-catalysts due to their suggestible band
      gap and structural properties. The generation of reactive oxygen species such as
      hydroxyl and superoxide radicals is the crucial factor in degradation of
      pollutant molecules. The rapid recombination of photo-generated electron-hole
      pairs impacts on the efficacy of semiconductors as photo-catalysts. The
      integration of properties of multi-walled carbon nanotubes (MWCNTs) with
      semiconductors is considered as imperative alternative strategy to boast the
      photocatalytic efficiency. The combinative merits of composites of MWCNTs and
      various semiconductor materials give new vista for water treatment and
      environmental protection. This review describes the scope of different types of
      MWCNT and semiconductor composites as photo-catalysts and their structure
      property relationships in oxidative degradation and mineralization of organic
      pollutants, in particular.

PMID- 30235626
TI  - Temporal trends of PCBs and DDTs in Great Lakes fish compared to those in air.
AB  - Regulations designed to lower the concentrations of PCBs and DDTs in the
      environment have been in place since the 1970s, but the levels of PCBs are still
      high enough to cause fish consumption advisories for Great Lakes fish. The levels
      of PCBs and DDTs have been tracked in these fish since about 1975, and the rates
      at which these age-adjusted concentrations have been decreasing over the period
      1999-2014 have been recently been estimated. This paper compares these rates to
      ones estimated from the entire data set (~1975-2014) and to rates estimated from
      changes in atmospheric concentrations, which have been tracked since 1992. In
      general the halving times (9-17 years for PCBs and 7-10 years for DDTs) estimated
      from the full fish dataset are similar to those estimated from the atmospheric
      data, suggesting that the atmospheric and the fish levels are coupled. The more
      recent, age-adjusted rates are sometimes significantly faster than those from the
      full fish and atmospheric datasets, suggesting that the air-water dynamic may now
      be changing.

PMID- 30235627
TI  - Coastal water quality assessment and groundwater transport in a subtropical
      mangrove swamp in Daya Bay, China.
AB  - Coastal water quality assessment is challenging due to the complex hydrological
      environment in mangrove swamps. Such assessment requires a good understanding of
      swamp hydrology and potential solute reactions. In this study, we investigated
      the concentration variations of a suite of major elements (Na+, K+, Ca2+, Mg2+,
      SO42-, HCO3- and Cl-), nutrients such as dissolved inorganic phosphorous (DIP)
      and silicate (DSi), and heavy metals (Cu, Zn, As, Hg, Cd, Pb and Cr) along a
      typical mangrove transect in Daya Bay, China. The transect comprises a tidal
      creek, a mudflat and two mangrove zones. The major elements exhibited various
      degrees of dilution and loss, such as losses of K+ due to uptake by mangrove
      trees and of SO42- due to microbial sulfate reduction. Numerical simulations of
      groundwater flow showed that the inland fresh groundwater can continuously
      discharge through the landward mangrove zone, where high concentrations of DIP
      and DSi occurred. However, the middle mangrove zone served as a sink of DIP and
      DSi due to the weak hydrodynamic environment. The spatial distribution of heavy
      metal concentrations showed that only Cu pollution occurred in the creek zone.
      The Metal Pollution Index (MPI) was developed to compare the enrichment
      capability of heavy metals at the different sampling sites. Results showed that
      the intertidal groundwater has the strongest heavy metal enrichment capability,
      followed by sea water, inland groundwater and river water. Within the intertidal
      zone, the creek zone has the highest MPI, followed by the mangrove zone and the
      mudflat zone. The local water circulation occurred around the creek should
      contribute the high MPI in the creek zone.

PMID- 30235628
TI  - Metal sorption studies biased by filtration of insoluble metal oxides and
      hydroxides.
AB  - Toxic metals in the environment are often remediated using sorption techniques,
      particularly in aquatic and drinking water systems. However, a review of over 30
      published sorption studies in the past two years alone revealed that the use of
      filtration to separate sorbed from unsorbed metals do not take into account metal
      hydroxide and oxide formation, and thus likely produce erroneous results. We
      quantified the effect of filtration on the removal of metal oxide/hydroxides from
      solution using a 0.45 MUm filter as a function of pH, initial metal concentration
      and ionic strength for As, Be, Cd, Cu, Cr, Pb and Zn. We found that even when the
      initial metal concentration was as low as 0.1 mg/L, up to 93% of metals in
      solution were removed and up to 100% removal was observed when the initial metal
      concentration was 5 mg/L at a pH of 7. If this was unaccounted for, precipitated
      metal oxide/hydroxide removed via filtration will be inaccurately attributed to
      metal sorption. Additionally, we demonstrate that speciation modeling can
      underestimate the pH at which insoluble metal species form and therefore can only
      be used to approximate metal precipitation, especially in complex matrices.
      Overestimating the sorption capacity of sorbent materials has major implications
      if these sorbents are used for the purification of drinking water or other vital
      environmental remediation efforts. We recommend sorption studies using filtration
      prepare the appropriate matrix-matched control samples to quantify potential
      metal oxide/hydroxide formation.

PMID- 30235629
TI  - Electrochemical oxidation disinfects urban stormwater: Major disinfection
      mechanisms and longevity tests.
AB  - Although electrochemical oxidation (ECO) has shown excellent potential for
      disinfecting wastewater and surface waters, its application on urban stormwater
      has been rarely tested. In order to improve stormwater ECO design, this paper
      explores the major inactivation processes using Boron Doped Diamond (BDD) and
      titanium Dimensional Stable Anodes (DSA). Both BDD and DSA showed comparable
      disinfection rates. The mechanism study suggested that BDD relied on hydroxyl
      radical and the presence of chloride ions, while DSA disinfected stormwater
      mainly via the production of free-chlorine. A deterioration study carried out at
      a catchment in Melbourne, showed a steady performance for BDD and revealed that
      DSA's performance degraded with time, likely linked to the high operational
      voltage required for specific chemistry of stormwater. Scanning Electron
      Microscopes and an Energy Dispersive X-ray Detector tests confirmed elemental
      losses occurred on the DSA surface, together with an aluminium/silicon coating
      layer potentially sourced from the stormwater clayish sediments. Furthermore,
      disinfection by-products in electrochemical disinfected stormwater using either
      BDD or DSA were at least one order of magnitude lower than the Australia Drinking
      Water Guidelines limits. The mechanism and long-term study demonstrated that
      careful anode selection is required as some anodes will deteriorate in stormwater
      matrices faster than others.

PMID- 30235630
TI  - Effect of poplar trees on nitrogen and water balance in outdoor pig production -
      A case study in Denmark.
AB  - Nitrate leaching from outdoor pig production is a long-standing environmental
      problem for surface and groundwater pollution. In this study, the effects of
      inclusion of poplar trees in paddocks for lactating sows on nitrogen (N) balances
      were studied for an organic pig farm in Denmark. Vegetation conditions, soil
      water and nitrate dynamics were measured in poplar and grass zones of paddocks
      belonging to main treatments: access to trees (AT), no access to trees (NAT) and
      a control without trees (NT), during the hydrological year April 2015 to April
      2016. Soil water drainage for each zone, simulated by two simulation models
      (CoupModel and Daisy), was used to estimate nitrate leaching from the zones in
      each paddock. N balances (input minus output) for the treatments were computed
      and compared. The results showed that, in terms of annual water balance and
      regardless of treatment, simulated evapotranspiration of poplar was 560-569 and
      489-498 mm for CoupModel and Daisy, respectively, and corresponding
      evapotranspiration of grass-clover was 250 and 400 mm, against precipitation of
      1076 mm. Simulated drainage below the root zone varied as 620-723 mm for Daisy
      and 568-958 mm for CoupModel, the higher end of the latter being probably
      overestimated. Annual nitrate leaching ranged from 32 kg N ha-1 in the poplar
      zone of NAT up to 289 kg N ha-1 in the control grass zone of NT. The poplar zone
      showed significantly lower nitrate leaching, by 75-80%, compared to the grass
      zone. For the control NT treatment, nitrate leaching was approximately 50% higher
      in the grass zone closest to the hut compared to the grass zone further away. NT
      treatment also had the largest surface N balance of 468 kg N ha-1 compared to 436
      and 397 kg N ha-1 for AT and NAT, respectively. When N losses by leaching and
      volatilisation were included, soil N balances were 118, 157 and 113 kg N ha-1 for
      AT, NAT and NT, respectively. Overall, the two simulation models were found
      useful tools for analyses of water balance for complex agroforestry systems. The
      findings collectively suggest that it is possible to decrease nitrate leaching
      from outdoor pig production on sandy soils by inclusion of poplar trees.
      Additional measures are nevertheless needed to reduce N losses on a mean area
      basis in paddocks with 20% tree cover.

PMID- 30235631
TI  - Health and ecological risk assessment of emerging contaminants (pharmaceuticals,
      personal care products, and artificial sweeteners) in surface and groundwater
      (drinking water) in the Ganges River Basin, India.
AB  - Pharmaceuticals, personal care products (PPCPs), and artificial sweeteners (ASWs)
      are contaminants of emerging concern commonly found in the aquatic environments.
      In India, studies reporting environmental occurrence of these contaminants are
      scarce. In this study, we investigated the occurrence and distribution of 15
      PPCPs and five ASWs in the river and groundwater (used untreated as drinking
      water) at several sites along the Ganges River. Based on the measured groundwater
      concentrations, we estimated the life-long human health risk from exposure to
      PPCPs through drinking. In addition, we estimated the risk of exposure to PPCPs
      and ASWs in the river water for aquatic organisms. The sum of detected PPCPs in
      the river water ranged between 54.7-826 ng/L, with higher concentrations in the
      severely anthropogenically influenced middle and lower reaches of the Ganges. The
      highest concentration among the PPCPs in the river water was of caffeine (743
      ng/L). The sum of detected ASWs in river water ranged between 0.2-102 ng/L.
      Similar to PPCPs, the sum of ASWs in the river water was higher in the middle and
      lower reaches of the Ganges. In groundwater, the sum of detected PPCPs ranged
      between 34-293 ng/L, whereas of ASWs ranged between 0.5-25 ng/L. Negligible risk
      for humans was estimated from PPCPs in the drinking groundwater sources along the
      Ganges River, whereas moderate risks to PPCPs and ASWs (namely: caffeine,
      sulfamethoxazole, triclocarban, triclosan, and sucralose) were estimated for
      aquatic organisms in the Ganges River.

PMID- 30235632
TI  - Study of the influence of the matrix characteristics over the photocatalytic
      ozonation of parabens using Ag-TiO2.
AB  - Parabens are widely used as antimicrobial and preservative in pharmaceutical and
      personal products. Their presence has been detected in rivers and wastewater
      treatment plants. Photocatalytic ozonation process using a low amount of 0.1 wt%
      Ag-TiO2 proved to be efficient on the degradation of a mixture of five parabens
      using a low transferred ozone dose (TOD). The pH effect was analyzed under acidic
      and neutral conditions. Also, the effect of hydroxyl radical scavenger on
      parabens degradation and on by-products formation was discussed. Hydroxyl radical
      present a significant role over parabens degradation and also on by-products
      formation. The reaction mechanism was analyzed using municipal wastewater as a
      matrix to infer about the behavior of the process at actual conditions. Municipal
      wastewater as a matrix clearly enhanced the parabens degradation when compared
      with the case where ultrapure water was used. In fact, the TOD required for total
      parabens degradation is lowered 10-20 mg/L of TOD. Therefore, to understand the
      main responsible species for this improvement, the effects of several ions
      naturally present in wastewater (HCO3-, Cl- and SO42-) were tested. According to
      the results it seems that sulfate radical improves the process, while chloride
      and bicarbonate radicals decrease the process efficiency. In terms of toxicity
      the luminescence inhibition for Vibrio fischeri was analyzed. The inhibition
      significantly decreased for treated spiked municipal wastewater.

PMID- 30235633
TI  - Influence of different agricultural management practices on soil microbial
      community over dissipation time of two herbicides.
AB  - Soil microbiology could be affected by the presence of pesticide residues during
      intensive farming, potentially threatening the soil environment. The aim here was
      to assess the dissipation of the herbicides triasulfuron and prosulfocarb,
      applied as a combined commercial formulation, and the changes in soil microbial
      communities (through the profile of phospholipid fatty acids (PLFAs) extracted
      from the soil) during the dissipation time of the herbicides under field
      conditions. The dissipation of herbicides and the soil microbial structure were
      assessed under different agricultural practices, such as the repeated application
      of herbicides (twice), in unamended and amended soils with two organic amendments
      derived from green compost (GC1 and GC2) and with non-irrigation and irrigation
      regimes. The results obtained indicate slower dissipation for triasulfuron than
      for prosulfocarb. The 50% dissipation time (DT50) decreased under all conditions
      for the second application of triasulfuron, although not for prosulfocarb. The
      DT50 values for both herbicides increased in the GC2 amended soil with the
      highest organic carbon (OC) content. The DT50 values decreased for prosulfocarb
      with irrigation, but not for triasulfuron, despite its higher water solubility.
      The herbicides did not have any significant effects on the relative population of
      Gram-negative and Gram-positive bacteria during the assay, but the relative
      abundance of Actinobacteria increased in all the soils with herbicides. At the
      end of the assay (215 days), the negative effects of herbicides on fungi
      abundance were significant (p < 0.05) for all the treatments. These
      microbiological changes were detected in non-irrigated and irrigated soils, and
      were more noticeable after the second application of herbicides. Actinobacteria
      could be responsible for the modification of herbicide degradation rates, which
      tend to be faster after the second application. This study makes a useful
      contribution to the evaluation of the soil environment and microbiological risks
      due to the long-term repeated application of herbicides under different
      agricultural management practices.

PMID- 30235634
TI  - The use of mid-infrared diffuse reflectance spectroscopy for acid sulfate soil
      analysis.
AB  - Good management of sulfide minerals and sulfuric acid in Acid Sulfate Soils (ASS)
      requires cost-effective rapid analytical data for their characterisation.
      However, the determination of properties in ASS samples using traditional
      laboratory techniques is expensive and time consuming. Excessive delays in
      analysis risks sample changes from oxidation. Mid-infrared (MIR) spectroscopy
      with multivariate regression offers a quicker and cheaper surrogate. This
      manuscript reports the prediction of some of the following key soil parameters in
      ASS characterisation using benchtop (Perkin Elmer) and handheld (ExoScan) diffuse
      reflectance MIR Fourier transform (DRIFT) spectrometers: Total Organic Carbon
      (TOC), Titratable Actual Acidity (TAA), Extractable Sulfate Sulfur (ESS), Reduced
      Inorganic Sulfur (RIS), Retained Acidity (RA), Acid Neutralising Capacity (ANC),
      and Lime Calculation (LC). Three sets of representative ASS soil profiles,
      comprising 132 samples from hyposulfidic, hypersulfidic and sulfuric materials,
      and covering a wide range of environments in South Australia were scanned under
      laboratory conditions. These were combined with reference laboratory data in
      partial least squares regression (PLSR) calibration models. The calibrations were
      validated by leave-one-out cross validation, with a further test set available
      for validation. Predictions with coefficient of determination (R2) > 0.75, were
      obtained for TOC (0.95), TAA (0.88), RIS (0.86), LC (0.76) and ANC (0.76), but
      models for ESS (0.66) and RA (0.41) were less satisfactory. The handheld
      spectrometer performed similarly to the benchtop spectrometer in terms of PLSR
      prediction accuracies with the potential for in-field sampling. Results thus
      confirmed the possibility of using MIR spectroscopy for the rapid and cost
      effective characterisation of ASS.

PMID- 30235635
TI  - Fast and environmental-friendly methods for the determination of polybrominated
      diphenyl ethers and their metabolites in fish tissues and feed.
AB  - Environmental-friendly, cost-effective and fast methods were developed and
      validated for the analysis of seven PolyBrominated Diphenyl Ethers (PBDEs) and
      eight methoxylated PBDEs (MeO-PBDEs) in three distinct seafood matrices (muscle,
      liver and plasma) and feed using a Quick, Easy, Cheap, Efficient, Rugged and Safe
      (QuEChERS) extraction approach for solid samples and a Dispersive Liquid-Liquid
      Microextraction method (DLLME) for plasma. Instrumental analyses were performed
      with gas chromatography coupled to triple quadrupole mass spectrometry using
      electron impact source (GC-EI-MS/MS) and negative ion chemical ionization (GC
      NICI-MS) to assess BDE-209. Statistical validation showed recoveries for all
      target substances near 100% with average Relative Standard Deviation (RSD) lower
      than 9% and recovery standards higher than 65% (average RSD below 20%). Average
      calculated Method Detection Limits (MDLs) were lower than 65 pg.g-1 wet weight
      (WW) for muscle, 5.35 ng.g-1 WW for liver, 4.50 ng.g-1 WW for feed, and 0.60
      ng.mL-1 for plasma samples. Quality assurance and quality control practices were
      comprehensively described. Methods scored high in an analytical Eco-scale, thus
      being classified as "an excellent green analysis". Finally, real seafood samples
      collected in local markets and local fishermen were analyzed. Positive samples
      presented both PBDEs and MeO-PBDEs in safe amounts (0.28-125.80 ng.g-1 WW) for
      human consumption.

PMID- 30235636
TI  - First steps in life cycle assessments of cities with a sustainability
      perspective: A proposal for goal, function, functional unit, and reference flow.
AB  - This study highlights the need and suggests some basis for working on the Life
      Cycle Assessment (LCA) of cities with a sustainability perspective. Cities are
      relevant actors in sustainable development and contribute to the generation of
      significant environmental impacts upstream and downstream their internal
      activity. LCA is precise in assessing environmental aspects of sustainability but
      lacks social and economic inputs. It is important to avoid problem shifting, even
      between the different dimensions of sustainability. A systematic literature
      review has been performed so as to extract the procedure for defining the goal,
      function, functional unit, and reference flow of a complex system. The existing
      literature is mainly product focused, although services are also considered
      somehow. The procedure for defining the abovementioned items is previously
      applied to a relatively simple system, a power generation plant, so as to find
      parallelisms to define those items for a complex system such as a city. To obtain
      a feasible (i.e., simplified) city Life Cycle Sustainability Assessment, the
      authors propose to introduce the social and economic aspects through the use of
      the City Prosperity Index (CPI) as technical performance within the FU of the
      city LCA. The CPI combined with the number of inhabitants is the normalization
      factor which is found to be more suitable to avoid problem shifting among
      sustainability dimensions and to avoid the interference of the number of
      inhabitants when comparing two different cities. An exemplification of the
      variation of the results after the application of these two factors in 18 cities'
      CO2-eq emissions is described. Even though this is not a large sample, it
      includes cities from different continents and levels of development and, thus it
      can be useful to see the how the suggested method is affecting cities' ranking.

PMID- 30235637
TI  - A steady-state analytical profile method for determining methane oxidation in
      landfill cover.
AB  - Gas concentration profiles of carbon dioxide (CO2), oxygen (O2), methane (CH4)
      and nitrogen (N2) are usually measured during tests investigating microbial
      aerobic methane oxidation in landfill cover. However, only qualitative/limited
      information can be obtained from gas concentration profiles by existing methods.
      A new method is proposed to determine methane oxidation in soil quantitatively
      and comprehensively, including methane oxidation efficiency, stoichiometry, gas
      transfer mechanism, methane generation rate and gas reaction rate distributions.
      Governing equations are established based on mass balance for O2, CO2, CH4 and N2
      at one-dimensional and steady-state condition. Gas transfer mechanisms considered
      include gas diffusion, advection and gas reaction. The method utilizes gas
      concentration profiles to determine gas diffusion for each gas component
      according to Fick's law. Then gas advections and reactions can be determined by
      mass balance. The method is validated by (i) published soil column tests
      investigating methane oxidation and (ii) a calibrated numerical model based on a
      selected soil column test. The new method is capable of determining methane
      oxidation efficiency, stoichiometry, gas transfer mechanism, methane generation
      rate and gas reaction rate distributions for CH4, CO2 and O2.

PMID- 30235638
TI  - Enhancement of ligninolytic enzymes production and decolourising activity in
      Leptosphaerulina sp. by co-cultivation with Trichoderma viride and Aspergillus
      terreus.
AB  - This work investigated fungal co-culture as inducer of ligninolytic enzymes and
      decolourising activity in the Colombian strain Leptosphaerulina sp., an
      ascomycete white-rot fungus isolated from lignocellulosic material. Aspergillus
      niger, Aspergillus fumigatus, Aspergillus terreus, Trichoderma viride, Fusarium
      sp. and Penicillium chrysogenum were tested as Leptosphaerulina sp. inducers. The
      best fungal combinations in terms of enzyme production, fungal growth and
      decolourising activity were selected from solid media experiments. Response
      surface methodology (RSM) was utilised to optimise enzyme production and
      decolourising activity in liquid media. Solid media assays evidenced T. viride
      and A. terreus as the best Leptosphaerulina sp. inducers. The RSM identified a
      triple co-culture inoculated with T. viride (1000 MUL) and A. terreus (1000 MUL)
      into a 7-day culture of Leptosphaerulina sp. as the best treatment. This triple
      combination significantly improved ligninolytic enzymes production and Reactive
      Black 5 dye removal when compared to the Leptosphaerulina sp. monoculture and
      previously used chemical inducers. These results demonstrated the potential of
      fungal co-culture as an environmentally-friendly method to enhance
      Leptosphaerulina sp. enzymes production and decolourising activity.

PMID- 30235639
TI  - Application of DGT/DIFS and geochemical baseline to assess Cd release risk in
      reservoir riparian soils, China.
AB  - As the sole drinking water source for Beijing City, Cd has been previously
      assessed as the major contaminant in Miyun Reservoir (MYR) riparian soils.
      However, the potential release risk of Cd in such soils, and the labile-Cd
      release-resupply process from the soil solid phase to solution after water
      impoundment remain poorly understood. We established a geochemical baseline
      concentration (GBC) of Cd in MYR riparian soils, combined with the diffusive
      gradient in thin films (DGT) technique and DGT-induced fluxes in soil (DIFS)
      model, to reveal a dynamic release-resupply process and influencing factors of
      labile Cd in riparian soils. The results showed that Cd GBC in riparian soils was
      0.12 mg/kg, which was higher than the Cd background value (BV) for Beijing. Using
      Cd GBC as BV to assess the Cd contaminant level, the geo-accumulation index
      showed that Cd in riparian soils was at the uncontaminated level. In addition, Cd
      in the soils belonged to the non-residual fraction using the Community Bureau of
      Reference method. Cd mobility coefficients (F1/CTotal-Cd) of soils at low
      elevation had relatively high values, implying that Cd may be released during the
      initial impoundment of the MYR. Moreover, correlation analysis was used to found
      the major influencing factors between DGT-labile Cd and several parameters. The
      results showed that the DGT-labile Cd was positively correlated to the reducible
      and oxidizable fraction, CDGT-Fe, and total organic carbon, illustrating that the
      release of Cd from soils was controlled by Fe oxides and organic matter. The
      resupply ability (R values) and DIFS model parameters revealed that Cd in MYR
      soils belonged to the partially sustained case, and the slow desorption rate
      suggested that the release risk of Cd was low in the MYR riparian soils.

PMID- 30235640
TI  - How can statistical and artificial intelligence approaches predict piping erosion
      susceptibility?
AB  - It is of fundamental importance to model the relationship between geo
      environmental factors and piping erosion because of the environmental degradation
      attributed to soil loss. Methods that identify areas prone to piping erosion at
      the regional scale are limited. The main objective of this research is to develop
      a novel modeling approach by using three machine learning algorithms-mixture
      discriminant analysis (MDA), flexible discriminant analysis (FDA), and support
      vector machine (SVM) in addition to an unmanned aerial vehicle (UAV) images to
      map susceptibility to piping erosion in the loess-covered hilly region of
      Golestan Province, Northeast Iran. In this research, we have used 22 geo
      environmental indices/factors and 345 identified pipes as predictors and
      dependent variables. The piping susceptibility maps were assessed by the area
      under the ROC curve (AUC). Validation of the results showed that the AUC for the
      three mentioned algorithms varied from 90.32% to 92.45%. We concluded that the
      proposed approach could efficiently produce a piping susceptibility map.

PMID- 30235641
TI  - Activated bio-chars derived from rice husk via one- and two-step KOH-catalyzed
      pyrolysis for phenol adsorption.
AB  - The activated bio-chars (AB) were successfully synthesized from rice husk by one-
      and two-step KOH-catalyzed pyrolysis. The two-step pyrolysis can produce the high
      yields of AB compared to the one-step pyrolysis. Moreover, the yield of AB
      decreased with the increase of the mass ratio of KOH and char, which had a
      significant effect on the development of the surface area and porosity of carbon.
      In particular, the AB derived from the two-step pyrolysis at 750 degrees C (mass
      ratio of KOH and char was 3) had the highest specific surface area
      (SBET=2138m2/g) with many micro-porous structures, which was favored for the
      phenol adsorption. The maximum adsorption capacity of AB2-3-750 reached 201mg/g
      because of its excellent surface porosity property. The phenol can be efficiently
      removed from water by only several minutes. The Langmuir model defined well the
      adsorption isotherm with a high correlation coefficient value, indicating a
      monolayer adsorption behavior. And the adsorption process defined well with the
      pseudo-second-order model. The phenol molecules passed into the internal surface
      via the liquid-film controlled diffusion, so the behavior of phenol adsorption
      onto the AB was predominantly controlled via the chemisorption. Furthermore, the
      functional groups on the outer surfaces of AB can attract the phenol molecules
      onto the internal surfaces via "pi-pi dispersion interaction" and "donor-acceptor
      effect".

PMID- 30235642
TI  - Cyanobacteria in small water bodies: The effect of habitat and catchment area
      conditions.
AB  - Cyanobacteria are an important component of microalgae communities in aquatic
      ecosystems, however, their response to environmental factors in different
      habitats and catchment areas of small water bodies is still not well recognised.
      We examined ponds from two types of surroundings (field vs. forest) in order to
      find the best triggers for the distribution of cyanobacteria species, and
      analysed different habitats (open water and macrophyte-dominated zones) to find
      the habitat preferences of cyanobacteria species. Our results underline the
      important role of habitats in the determination of the abundance of cyanobacteria
      species in small water bodies. Cyanobacteria as a group preferred macrophyte
      dominated sites with stable water column conditions, which to lesser extent were
      inhabited by representatives of other systematic groups of algae. The co
      occurrence of many cyanobacteria species and zooplankton in the studied ponds may
      have indirectly resulted from biotic interactions in the food web. In the open
      water a positive relationship between zooplankton and cyanobacteria suggests
      stimulation of their development through the elimination of smaller edible taxa
      or by nutrient resupply through zooplankton excretion. The type of catchment area
      also impacted the cyanobacterial community. Field ponds with significantly higher
      values of pH and NO3 were characterised by a higher abundance of cyanobacteria
      compared with ponds within the forest catchment. A positive relationship between
      pH and cyanobacteria indicates that they raise pH during photosynthesis. However,
      some species were negatively associated with water temperature and occurred
      exclusively only in forest ponds. The study revealed that cyanobacteria in small
      water bodies can be a valuable indicator of important ecosystem conditions.
      Despite the fact that their prevalence in agricultural ponds may confirm their
      potential as an indicator of pollution, their high diversity associated with
      macrophytes contributes to an increase of overall landscape biodiversity.

PMID- 30235643
TI  - Evaluation of geochemical processes and nitrate pollution sources at the
      Ljubljansko polje aquifer (Slovenia): A stable isotope perspective.
AB  - The Ljubljansko polje aquifer, which is the main supply of drinking water for the
      local population in Ljubljana, Slovenia is highly vulnerable to anthropogenic
      pollution. In this study, the geochemistry of major constituents including
      nitrate concentrations and the dual isotopes of nitrate were used to ascertain
      the spatial distribution of processes and nitrate sources in the groundwater from
      seven wells at three different water supplies: Klece, Hrastje and Jarski prod.
      The groundwater is of the Ca2+-Mg2+-HCO3- type approaching equilibrium with
      respect to dolomite and are moderately supersaturated with calcite. The
      groundwater nitrate concentrations ranged from 5.32 to 50.1 mg L-1 and are well
      above the threshold value for anthropogenic activity (3 mg L-1). The delta15NNO3
      values ranged from 1.4 to 9.70/00, while delta18ONO3 values were from 6.3 to
      34.60/00. Based on isotope mixing model three sources of nitrate were identified:
      atmospheric deposition, fertilizers and soil nitrogen. At Klece 8, Klece 12 and
      Jarski prod 3 the low delta15NNO3 and high delta18ONO3 values result from
      pristine nitrate sources, while in Hrastje 3 and Klece 11 equal amounts of
      nitrate derived from soils with mixed fertilization and sewage. The data also
      indicate that the main sources of high nitrate concentrations in groundwater are
      from fertilizers and sewage-manure (comprising up to 64%). Such levels occurred
      in the Hrastje and Klece 11 wells where precipitation is the main source of
      groundwater. Nitrate derived from atmospheric deposition accounted for
      approximately 10% of the nitrate in the groundwater. The message from this study
      is that to reduce the nitrogen load and improve water quality will involve
      containment and the careful management of sources from urban and agriculture
      inputs such as sewage-manure and fertilizers.

PMID- 30235644
TI  - Economic, social, and environmental evaluation of energy development in the Eagle
      Ford shale play.
AB  - This research investigates the relation between water, energy, and transportation
      systems, using the growing hydraulic fracturing activity in the Eagle Ford shale
      play region of southwest Texas in which the local water systems and road
      infrastructure were not designed for the frequent transport of water into the
      production site and of produced gas and oil from the site as are often required
      for hydraulic fracturing. The research: 1) quantifies the interconnections
      between water, energy, and transportation systems specific to the Eagle Ford
      shale region; 2) identifies and quantifies the economic, social, and
      environmental indicators to evaluate scenarios of oil and gas production; and 3)
      develops a framework for analysis of the economic, societal, and long term
      sustainability of the sectors and 4) an assessment tool (WET Tool) that estimates
      several economic indicators: oil and natural gas production, direct and indirect
      tax revenues, and average wages for each scenario facilitates the holistic
      assessment of oil and gas production scenarios and their associated trade-offs
      between them. Additionally, the Tool evaluates these social and environmental
      indices, (water demand, emissions, water tanker traffic, accidents, road
      deterioration, and expected average employment times). Scale of production is
      derived from the price of oil and gas; government revenues from production
      fluctuations in relation to rise and fall of the oil and gas market prices. While
      the economic benefits are straightforward, the social costs of shale development
      (water consumption, carbon emissions, and transportation/infrastructure factors),
      are difficult to quantify. The tool quantifies and assesses potential scenario
      outcomes, providing an aid to decision makers in the public and private sectors
      that allows increased understanding of the implications of each scenario for each
      sector by summarizing projected outcomes to allow evaluation of the scenarios and
      comparison of choices and facilitate the essential dialogue between these
      sectors.

PMID- 30235645
TI  - The use of calcium carbonate-enriched clay minerals and diammonium phosphate as
      novel immobilization agents for mercury remediation: Spectral investigations and
      field applications.
AB  - We used calcium carbonate-enriched clay minerals (CECM) and diammonium phosphate
      (DAP) as immobilization agents for mercury (Hg) immobilization. The effects of
      CECM, DAP, or both in different amounts and ratios, as well as pH and initial Hg
      concentrations, on Hg removal from solutions were investigated. The removal
      mechanism was revealed using transmission electron microscope with energy
      dispersive X-ray (TEM-EDX) spectroscopy, and extended X-ray absorption fine
      structure spectroscopy (EXAFS). The performance of CECM and DAP under field
      conditions was also studied. The results showed that application of CECM and DAP
      at a ratio of 50:1 (w/w) removed over 90% of Hg from solutions containing 1.8 MUM
      Hg2+, which was 9- or 2.6-fold higher than solely DAP (<10%) or CECM (34%<),
      respectively. Mercury removal by CECM and DAP was weakly affected by pH values
      between 4 and 10, and their maximum Hg removal capacity was 37 mg g-1. Both TEM
      EDX and EXAFS results showed that the precipitate of Hg with phosphorus
      associated minerals might be the primary mechanism of Hg removal by CECM and DAP.
      Results from the field trial showed that application of CECM and DAP decreased
      soil bioavailable Hg contents, but did not affect contents of organic matter
      bound Hg or residual Hg fractions, as compared with control and initial soils.
      Application of CECM and DAP resulted in dramatic reductions (40%-53%) of Hg in
      the edible tissues of Brassica chinensis and Raphanus raphanistrum in comparison
      to the non-treated control. We conclude that CECM and DAP offer a promising
      method for in situ remediation of Hg-contaminated farmlands in southwest of
      China.

PMID- 30235646
TI  - Using a hierarchical model framework to assess climate change and hydropower
      operation impacts on the habitat of an imperiled fish in the Jinsha River, China.
AB  - Climate change and hydropower operations affect hydrological regimes at regional
      basin scales and impact hydrodynamics and habitat conditions for biota at the
      river reach scale. The present study proposes a hierarchical modeling framework
      for predicting and analyzing the impacts of climate change and hydropower on fish
      habitats. The approach couples multi-scale climate, hydrological, water
      temperature, hydrodynamic and habitat suitability models and was applied to a
      reach of the Jinsha River. Flow discharge and water temperature were predicted in
      the study area for a baseline scenario and three climate change scenarios, and
      each considered the presence and absence of impacts caused by hydropower
      operation. The impacts of flow discharge and water temperature variations on
      spawning and juvenile Coreius guichenoti, an imperiled warm-water fish in the
      Jinsha River Basin (JRB), were evaluated using a fuzzy logic-based habitat model.
      The results showed that habitat suitability and available usable area for the
      fish increased due to climate change, and water temperature rising was the main
      influencing factor. Water temperature decrease induced by hydropower operation in
      the spawning periods resulted in the reduction of available habitat area.
      However, climate change reduced the negative effects generated by hydropower
      operation, and the available habitat area for the fish would still be expected to
      increase under the combined impacts of climate change and hydropower operation in
      the future. It is predicted that water warming, as a result of climate change, is
      likely to eliminate the spawning postponement effect generated by hydropower
      operation on Coreius guichenoti as well as other warm-water fish species in the
      JRB. In contrast, water warming induced by climate change is likely to exacerbate
      the negative effects of hydropower operation on the spawning activity of cold
      water fish species in the JRB. The present study provides a scheme to predict the
      impacts of climate change and hydropower on other organisms in river ecosystems.
      The results are beneficial for the development of long-term and adaptive
      conservation and restoration measures for aquatic ecosystems.

PMID- 30235647
TI  - Hydraulic study of a non-steady horizontal sub-surface flow constructed wetland
      during start-up.
AB  - This paper describes the hydraulic performance of a start-up, pilot-scale,
      horizontal sub-surface flow constructed wetland (CW), located outdoors at the
      Helmholtz UFZ, Leipzig. This paper aims to investigate the impact of the method
      of hydraulic calculation in a pilot-scale system. Impulse-response tracer tests
      were conducted at multiple depths and locations throughout the system and the
      uranine concentration was measured using a fluorometer. In addition, the
      volumetric flow rate was closely monitored and climatic data was gathered to
      support the hydraulic results. Werner and Kadlec's modified residence time
      distribution (RTD) theory (originally developed for systems with large flow rate
      and volume fluctuations) was applied and the results compared to those obtained
      using classic RTD theory. Progressive uranine dispersion, broadening of the RTD
      base, a change in peak shape and extended tailing were observed with increasing
      distance. All of these factors indicated deviation from plug flow and mixing
      effects with low-to-moderate dead volume. As this was a non-steady flow system,
      application of modified RTD theory ensured that the first moments of the
      normalized breakthrough curves and RTD functions were always unity. The Student's
      t-test (95% confidence) showed that the outlet RTDs calculated assuming steady
      flow were significantly different, but those determined using the modified theory
      were closely comparable. In general, a decrease in flow rate from inlet to outlet
      was observed and fluctuations in the outflow were linked to climatic conditions.
      August was characterized by the highest temperatures, high global radiation and
      high rates of evapotranspiration. Low or no outflow was recorded in conjunction
      with high evapotranspiration. The lowest temperatures, low global radiation, low
      evapotranspiration and high humidity were recorded in October, as well as the
      second highest rainfall (82 mm) after June (115 mm). Surges in outflow were
      observed with rain events.

PMID- 30235648
TI  - Evaluation of combined toxicity of Siduron and cadmium on earthworm (Eisenia
      fetida) using Biomarker Response Index.
AB  - Agrochemicals and heavy metals are widespread contaminants in urban soil and
      could co-exist as mixture, which could cause unexpected risk to terrestrial
      organism. To assess the joint effect of herbicide Siduron and Cd, a battery of
      sub-lethal biomarkers was studied using earthworm ecotoxicological assay. Most
      selected biomarkers appeared significant but complicated responses with the
      increasing concentration of contaminants after 28-day exposure. In order to
      quantify the overall effect of the mixture contaminants, Biomarker Response Index
      (BRI) was used to integrate the multiple responses. Concentration Addition Index
      (CAI) and Effect Addition Index (EAI) were introduced to assess types of joint
      effect. Results showed significantly dose-effect responses between BRI and
      contaminant exposure concentrations. Integrated toxicity increased obviously
      under joint treatments of Siduron and Cd compared to their individual treatments.
      According to CAI, a clear antagonism was observed at relatively lower effects and
      gradually transformed to slight synergism with an increase of effects, while EAI
      showed the joint effect of addition at the whole range of effect levels. Thus,
      compared to the simple analysis of those complicated responses, BRI is an
      effective method to determine the integrated toxicity of mixture and its
      combination with joint effect indices (CAI and EAI) provides more worthy risk
      assessment on toxicity interaction among compounds.

PMID- 30235649
TI  - Redistribution of methane emission hot spots under drawdown conditions.
AB  - In the context of reservoirs, sediment trapping, and aquatic greenhouse gas (GHG)
      production, knowledge about the distribution of hot and low spots is essential
      for improved measurement strategies. It is also a key to a precise assessment of
      the GHG emissions of each reservoir. Large numbers of reservoirs are used mainly
      for hydroelectric power generation and, hence, affected by strong changes in
      water level. Drawdown events may lead to significant changes in spatial sediment
      and organic carbon distribution and, consequently, strongly alter the GHG
      emission patterns of the water body. We combined hydroacoustic sediment
      classification, sediment magnitude detection, and ebullition flux assessment with
      in-situ pore water investigations and sediment coring to detect ebullition
      distribution patterns after strong reservoir drawdown. The research was conducted
      in the Capivari Reservoir in the southeast of Brazil, which was affected by up to
      15 m of drawdown within the last 10 years. Results show severe changes in
      sediment accumulation and composition. The focusing of sediment divides the
      reservoir in extreme hot and low spots. Methane pore water concentrations are
      highly correlated with acoustic backscatter values (r2 = 0.97) as well as with
      the organic carbon content (r2 = 0.55) and allow for a precise detection of the
      newly created emission patterns. Highly productive sediment could be acoustically
      distinguished from non-productive areas. Only 23.6% of the reservoir surface
      produced 64% of the detected bubbles. An organic carbon content in the sediment
      of 2.4% was found to be a prerequisite for the formation of GHG emission hot
      spots. These findings may help to complement the still insufficient knowledge of
      methane ebullition fluxes from reservoirs with changing water levels.

PMID- 30235650
TI  - Iron-organic matter complexes accelerate microbial iron cycling in an iron-rich
      fen.
AB  - The accessibility of iron (Fe) species for microbial processes is dependent on
      solubility and redox state, which are influenced by complexation with dissolved
      organic matter (DOM) and water-extractable organic matter (WEOM). We evaluated
      the complexation of these pools of organic matter to soluble Fe(II) and Fe(III)
      in the slightly acidic Schloppnerbrunnen fen and subsequent effects on Fe(II)
      oxidation and Fe(III) reduction. We found the majority of soluble Fe(II) and
      Fe(III) is complexed to DOM. High-resolution mass spectrometry identified
      potential complexing partners in peat-derived water extracts (PWE), including
      compound classes known to function as ligands or electron shuttles, like tannins
      and sulfur-containing compounds. Furthermore, we observed clear differences in
      the stability of Fe(II)- and Fe(III)-DOM, with more labile complexes dominating
      the upper, oxic layers (0-10 cm) and more stable complexes in lower, anoxic
      layers (15-30 cm). Metal isotope-coded profiling identified a single potential
      chemical formula (C42H57O13N9Fe2) associated with a stable Fe-DOM complex.
      Fe(III) reduction and Fe(II) oxidation incubations with Geobacter sulfurreducens
      PCA and Shewanella oneidensis MR-1 or Sideroxydans CL-21, respectively, were used
      to determine the influence of Fe-DOM complexes on Fe cycling rates. The addition
      of PWE led to a 2.3-fold increase in Fe(III) reduction rates and 0.5-fold
      increase in Fe(II) oxidation rates, indicating Fe-DOM complexes greatly influence
      microbial Fe cycling by potentially serving as electron shuttles. Molecular
      analyses revealed Fe(III)-reducing and Fe(II)-oxidizing bacteria co-exist across
      all depths, in approximately equal proportions (representing 0.1-1.0% of the
      total microbial community), despite observed changes in redox potential. The
      activity of Fe(III)-reducing bacteria might explain the presence of the detected
      Fe(II) stabilized via complexation with DOM even under oxic conditions in upper
      peat layers. Therefore, these Fe(II)-DOM complexes can be recycled by
      microaerophilic Fe(II)-oxidizers. Taken together, these results suggest Fe-DOM
      complexation in the fen accelerates microbial-mediated redox processes across the
      entire redox continuum.

PMID- 30235651
TI  - Long term effect of nitrogen addition on understory community in a Chinese boreal
      forest.
AB  - Increasing atmospheric nitrogen (N) deposition is an important driver of
      biodiversity change. By conducting an eight-year N addition experiment (0, 20, 50
      and 100 kg N ha-1 yr-1), we investigated the long-term effect of simulated N
      deposition on understory species composition and richness in a boreal forest,
      northeast China. We found that moss cover decreased significantly with increasing
      N addition. N addition had no significant effect on vascular plants species
      richness but changed the plant community composition. The relative coverage of
      evergreen shrubs decreased, while that of graminoids increased under high-level N
      addition (100 kg N ha-1 yr-1). Under the high-level N treatment, Deyeuxia
      angustifolia cover increased significantly after 4 years, while that of Vaccinium
      vitis-idaea decreased significantly after 3 years and almost disappeared after 5
      years. The negative effect of N addition on mosses and evergreen shrubs
      accumulated over time, while the positive effect on graminoids increased during
      the first 4 years and did not change significantly thereafter. Our results
      suggest that the effect of N deposition varies across functional groups and
      shifts over time.

PMID- 30235652
TI  - Distribution of agricultural pesticides in the freshwater environment of the
      Guayas river basin (Ecuador).
AB  - The rapid increase and transition to more intensive agricultural activities in
      developing nations are often leading to misuse and overuse of pesticides, making
      their environment vulnerable for pesticide accumulation. In the present study,
      the Guayas river basin was taken as a representative case study to evaluate
      pesticide contamination of the Ecuadorean freshwater environment. Pesticide
      contamination was determined at 181 sampling sites by a multi-residue method
      using solid phase extraction (SPE) and pesticide residues were linked with
      agricultural land use activities to identify the main pollution sources.
      Moreover, the biological water quality status based on macroinvertebrate
      communities was determined at every location and the relation with the occurrence
      of pesticide residues was further investigated. Results showed that pesticide
      contamination of the freshwater environment was widely present in the Guayas
      river basin with detections at 108 sampling sites (60%). A total of 26 pesticide
      products were identified. Most frequently detected pesticides included cadusafos
      (62 locations), butachlor (21 locations) and pendimethalin (21 locations), with
      concentrations up to 0.081, 2.006 and 0.557 MUg.L-1 respectively. Pesticide
      residues detected in this study did not significantly influence the biological
      water quality (p = 0.69), but were observed to be positively correlated with
      ammonium concentrations, supporting the assumed combined application of chemical
      fertilizers and pesticides in agriculture. These pesticide residues were also
      associated with one or more agricultural crops, with in particular the banana and
      rice industries identified as major pollution sources. Both high consumption
      rates and non-specific application methods, such as aerial spraying of banana
      plantations and application directly into the water layer of irrigated rice
      fields, may attribute to pesticide contamination of the freshwater environment of
      the Guayas river basin. It is therefore suggested that measures, e.g. legal
      regulations and awareness campaigns, taken to prevent environmental pollution and
      accumulation of pesticides primarily focus on these industries.

PMID- 30235653
TI  - Reduction of circulating lymphocyte count is a predictor of good tumor response
      after neoadjuvant treatment for rectal cancer.
AB  - Systemic inflammatory indices are correlated with poor prognosis in cancer
      patients. The presence of lymphocytes in and around the tumor tissue is a
      predictor in rectal cancer. We aimed to explore the mechanism underlying the
      changes in circulating lymphocyte during neoadjuvant therapy and the way in which
      the count correlates with tumor response.Around 307 patients from FOWARC trial
      and 64 patients from FORTUNE trial were included in the training and validation
      group. Circulating lymphocyte count was recorded before neoadjuvant therapy and
      before rectal surgery. Receiver operating characteristic (ROC) curve analysis was
      performed to determine the optimal cut-off value of the reduction of lymphocytes.
      A logistic regression model was obtained in multivariate analysis.The blood
      absolute number of lymphocyte before and after therapy had no correlation with
      tumor response. However, total lymphocyte count (TLC) reduction was significantly
      higher in good response group (39.81% vs 33.31% P = .032) in the FOWARC cohort.
      The optimal cut-off value for TLC was 24.96%. Age, tumor length, and TLC
      reduction (P = .005, OR = 2.009, 95%CI 1.240-3.254) were significant factors for
      tumor regression in multivariate analysis. In the FORTUNE cohort, TLC reduction
      was the only significant factor for tumor regression in both univariate (P =
      .032, OR = 3.434, 95%CI 1.111-10.614) and multivariate analysis (P = .046, OR =
      3.361, 95%CI 1.024-11.035).Circulating lymphocyte count decreases during
      neoadjuvant therapy for locally advanced rectal cancer, and it is associated with
      better tumor regression. It may be involved in the immune response provoked by
      radiotherapy and chemotherapy.

PMID- 30235654
TI  - The efficacy of gabapentin in reducing pain intensity and morphine consumption
      after breast cancer surgery: A meta-analysis.
AB  - BACKGROUND: The purpose of this meta-analysis from randomized controlled trials
      (RCTs) was to determine the efficacy and safety of the preoperative use of
      gabapentin for the treatment of acute and chronic postoperative pain following
      breast cancer surgery. METHODS: In November 2017, a systematic computer-based
      search was conducted in PubMed, Embase, Web of Science, Cochrane Library, and
      Google databases. RCTs comparing gabapentin with placebo in patients undergoing
      breast cancer surgery were retrieved. The primary endpoint was the visual analog
      scale (VAS) after surgery and 24 hours after surgery and total morphine
      consumption. The secondary outcomes were incidence of chronic pain and
      complications (the incidence of nausea). Software Stata 12.0 was used for meta
      analysis. RESULTS: Finally, 9 RCTs were included in the meta-analysis. Results
      indicated that gabapentin was associated with reduced pain scores after surgery
      and 24 hours after surgery. Meanwhile, oral gabapentin was associated with a
      reduction of the total morphine consumption after breast cancer surgery.
      Similarly, gabapentin was associated with a reduction in the incidence of chronic
      pain and the incidence of nausea. CONCLUSIONS: Preoperative use of gabapentin was
      able to reduce acute and chronic postoperative pain, total morphine consumption
      and the occurrence of nausea following breast cancer surgery. Further studies
      should determine the optimal dose of gabapentin for pain control after breast
      cancer surgery.

PMID- 30235655
TI  - Factors influencing the contamination rates of the conjunctival swabs and organ
      culture media of human donor eyes.
AB  - This study assessed the influence of donor, environmental, and logistical factors
      on the contamination rates of the conjunctival swabs and organ culture media of
      human donor eyes.In total, 1008 conjunctival swabs and 418 organ culture media
      samples from 504 consecutive human donor eyes were analyzed. Cross-tabulation,
      chi-squared tests, and Fisher's exact tests were used to assess the influence of
      the different factors on the contamination rates of the conjunctival swabs and
      organ culture media.The overall contamination rates were 28.4% for the
      conjunctival swabs and 1.0% for the organ culture media. A prolonged time between
      death and the conjunctival swab collection was associated with an increased
      conjunctival swab contamination rate [odds ratio (OR) = 1.9, 95% confidence
      interval (CI) = 1.2-3.0, P = .007]. The highest conjunctival swab contamination
      rate was found in the corneas procured in external institutions (outside the
      university hospital) (44.1%, OR = 3.6, 95%CI = 1.5-8.4, P = .003).
      Hospitalization times of 2 to 7 days prior to death were associated with an
      increased conjunctival swab contamination risk (OR = 2.6, 95%CI = 1.1-5.8, P =
      .021). However, the sex, age, cause of donor death, differentiation between
      septic and aseptic donors, differentiation between heart-beating brain-dead
      multiorgan donors and cadaveric donors, a warmer mean monthly temperature, and
      death to corneoscleral disc excision time did not significantly increase the
      conjunctival swab contamination risk. In addition, none of these factors affected
      the organ culture media contamination risk. Moreover, a positive conjunctival
      swab did not significantly increase the media contamination risk (P = .08).
      Surprisingly, the microorganisms causing media contamination were present at 50%
      of the amount detected on the conjunctival surface of the respective donor eye.A
      prolonged time between death and the conjunctival swab collection, a
      hospitalization time of 2 to 7 days prior to death, and corneal collection
      outside the university hospital seemed to be the main factors responsible for an
      increased conjunctival swab contamination risk. In addition, our investigation
      illustrated that a positive conjunctival swab is not a strong indicator for organ
      culture media contamination. Critical discussion is necessary regarding the
      validity of conjunctival swabs as prognostic parameters for organ culture media
      contamination.

PMID- 30235656
TI  - Modifying and evaluating efficacy of interactive computerized program using
      motion tracking technology to improve unilateral neglect in patients with chronic
      stroke.
AB  - BACKGROUND: To modify and evaluate the efficacy of a computerized visual
      perception rehabilitation program using interactive motion tracking technology
      with unilateral neglect after chronic stroke. METHODS: Study design is single
      blinded (analyst-blinded) controlled prospective clinical trial. Subjects are 16
      patients with chronic stroke and unilateral neglect for over 6 months and 19
      healthy volunteers. We modified our previous program to 9 tasks with built-in
      scoring system, and the subjects performed 3 sessions per week, 30 minutes per
      session for 4 weeks. RESULTS: Scores for the Modified Barthel Index (MBI), Mini
      Mental State Examination (MMSE), Motor-free Visual Perception Test (MVPT), Line
      bisection test, Star cancellation test, Forward Digit Test, and Backward Digit
      Test showed significant improvement at the end of the sessions in the patient
      group. By comparing the parameters of built-in scoring system of each task among
      the control group, the first session of training in the patient group, and the
      last session of training in the patient group, we categorized the parameters for
      optional measurement to determine the effect of training or to be a candidate for
      evaluative use. CONCLUSIONS: Our modified computerized visual perception
      rehabilitation program using improved unilateral neglect in patients post-stroke.
      Built-in scoring system in this program was helpful to assess availability of it
      more objectively.

PMID- 30235657
TI  - A CARE-compliant article: Extranasal glial heterotopia in a female infant: A case
      report.
AB  - RATIONALE: Nasal glial heterotopia is a rare type of neoplasm consisting of
      meningothelial and/or neuroglial elements. PATIENT CONCERNS: A 17-month-old
      female infant was evaluated for treatment for a congenital mass present since
      birth on the right side of the nasal dorsum. DIAGNOSES: The patient was
      preoperatively diagnosed with a congenital extranasal neoplasm. INTERVENTIONS:
      Surgery was performed under general anesthesia, and the mass was completely
      resected. The tissue was sent for histological examination, and the diagnosis was
      of extranasal glial heterotopia. OUTCOMES: The surgical outcome was good, and no
      surgical site infection was recorded. After 6 months of follow-up, the girl was
      asymptomatic with no recurrence. LESSONS: Surgical excision, a curative method
      used to address extranasal glial heterotopia, resulted in no recurrence during
      the clinical follow-up period. The potential for an intracranial connection must
      always be kept in mind when considering how to surgically treat a congenital
      midline mass to prevent the risk of cerebrospinal fluid leakage.

PMID- 30235658
TI  - Changes of intraocular pressure after cataract surgery in myopic and emmetropic
      patients.
AB  - To investigate the intraocular pressure (IOP) changes after cataract surgery, and
      its relationship with refractive conditions.IOP after phacoemulsification with
      intraocular lens (IOL) implantation was retrospectively reviewed. Patients were
      classified into 3 groups by refractive conditions: emmetropia, mild to moderate
      myopia, and high myopia. Basic information was collected including age, sex,
      place of IOL, and operating surgeon, with IOP and refractive conditions measured
      before surgery, and 1, 7, 30, and 90 days after surgery.The study comprised 353
      eyes from 353 patients, of which 175 were emmetropia, 130 were mild to moderate
      myopia, and 48 were high myopia. A lower IOP than baseline was observed at 7, 30,
      and 90 days after surgery in emmetropic and mild to moderate myopia, while in
      high myopia, IOP was instable from 1 to 30 days, and reduced only in 90 days
      after surgery. Changes of IOP was more significant from 1 to 7 days in emmetropic
      and mild to moderate myopic patients, but from 30 to 90 days in high myopia.
      Patients over 75 showed a lower IOP at each follow-up than patients younger and
      female showed a higher baseline IOP than male. Different surgeons might influence
      the IOP fluctuation at first 90 days but not the final IOP.All patients with
      different refractive conditions showed a remarkably lower IOP at 90 days after
      cataract surgery. However, high myopia lowered the speed of IOP reduction, which
      might be explained by the anatomical changes of eye structure.

PMID- 30235659
TI  - Successful treatment of acquired hemophilia A associated with immune
      thrombocytopenia and joint hemarthrosis: A case report and literature review.
AB  - INTRODUCTION: Acquired hemophilia A (AHA) is a rare bleeding disease caused by
      autoantibodies against factor VIII (FVIII). Spontaneous bleeding symptoms usually
      affect the skin, musco, muscle, and internal organs, while joint hemarthrosis in
      AHA is an extremely rare manifestation. AHA may have an autoimmune cause and is
      often associated with autoimmune disease, but no demonstrable platelet impairment
      was found in AHA patients. We report a patient with AHA complicated with a right
      shoulder joint hemarthrosis and immune thrombocytopenia. The patient was treated
      with fresh frozen plasma (FFP) and human prothrombin complex concentrate (hPCC)
      to control the active bleeding. Simultaneously this patient firstly accepted
      cyclophosphamide combined with prednisone to eradicate the inhibitor, while the
      treatment effect of cyclophosphamide combined with prednisone was not
      satisfactory. At last, she was successfully treated through the use of an anti
      CD20 monoclonal antibody. CONCLUSION: AHA is an autoimmune disease and can co
      exist with immune cytopenia besides connective tissue disease (CTD). Joint
      hemarthrosis is not specific to congenital hemophilia and mainly related to the
      extent of prolonged aPTT and weight loading of joint in AHA. When the first-line
      therapy of cyclophosphamide combined with prednisone is not enough to eradicate
      the inhibitor, especially for a higher inhibitor titer, anti-CD20 monoclonal
      antibody could play an important role.

PMID- 30235660
TI  - Peritoneal epithelioid angiosarcoma: A case report.
AB  - INTRODUCTION: Peritoneal angiosarcoma is an extremely rare sarcoma (0.01287%
      incidence per 100,000) with an aggressive course and a poor prognosis. In this
      case, the manifestation of peritoneal angiosarcoma was ascites, which caused
      difficulty in early diagnosis and the diagnosis of peritoneal angiosarcoma, was
      made only after the surgery. PATIENT CONCERNS: A 61-year-old man working in
      Mainland China presented with a 1-month history of abdominal distension. A
      contrast-enhanced abdominal computed tomography (CT) scan revealed peritoneal
      carcinomatosis with massive ascites. However, his tuberculosis (TB) polymerase
      chain reaction was negative. The ascites cell block and cytology also revealed
      negative for malignant cells. The patient underwent intra-abdominal tumor
      excision. After the operation, the patient's blood pressure (BP) dropped. Due to
      the state of shock, he was transferred to an intensive care unit (ICU).
      DIAGNOSES: According to the pathology report, the neoplastic cells were positive
      for cytokeratin, cluster of differentiation 31 (CD31), cluster of differentiation
      34 (CD34), and negative for cytokeratin 7 (CK7), cytokeratin 7 (CK20). Therefore,
      the diagnosis of epithelioid angiosarcoma was made. INTERVENTIONS: The patient
      took 400 mg of Pazopanib once a day. OUTCOMES: Even though vasopresser was used,
      the patient's BP was still low. Finally, he expired. LESSONS: Initialy, the
      patient presented with abdominal distension and large amount of ascites in the
      beginning. TB peritonitis was highly suspected after the abdominal CT scan.
      Therefore, surgical procedures would be essential in the identification of proper
      diagnosis. In the future, the diagnosis of peritoneal epithelioid angiosarcoma
      should also be taken into consideration for patients with abnormal ascites
      besides the common diagnoses of TB, liver cirrhosis, and infection.

PMID- 30235661
TI  - Assessment of graft perfusion and oxygenation for improved outcome in esophageal
      cancer surgery: Protocol for a single-center prospective observational study.
AB  - INTRODUCTION: The main cause of anastomotic leakage (AL) is tissue hypoxia, which
      results from impaired perfusion of the pedicle stomach graft after esophageal
      reconstruction. Clinical judgment is unreliable in determining graft perfusion.
      Therefore, an objective, validated, and reproducible method is urgently needed.
      Near infrared fluorescence perfusion imaging using indocyanine green (ICG) is an
      emerging and promising modality. This study's objectives are to evaluate the
      feasibility of quantification of ICG angiography (ICGA) to assess graft perfusion
      and to validate ICGA by comparison with hemodynamic parameters, blood and tissue
      expression of hypoxia-induced markers, and tissue mitochondrial respiration
      rates. And, second, to evaluate its ability to predict AL in patients after
      minimally invasive esophagectomy (MIE). METHODS: Patients (N = 70) with
      resectable esophageal cancer will be recruited for standard MIE. ICGA will be
      performed after graft creation and thoracic pull-up. Dynamic digital images will
      be obtained starting after intravenous bolus administration of ICG. The resulting
      images will be subjected to curve analysis and to compartmental analysis based on
      the adiabatic approximation to tissue homogeneity kinetic model. The calculated
      perfusion parameters will be compared to intraoperative hemodynamic data to
      evaluate the effects of patient hemodynamics. To verify whether graft perfusion
      represents tissue oxygenation, ICGA perfusion parameters will be compared with
      systemic and serosa lactate from the stomach graft. In addition, perfusion
      parameters will be compared to tissue expression of hypoxia-related markers and
      mitochondrial chain respiratory rate. Finally, the ability of functional,
      histological, and cellular perfusion and oxygenation parameters to predict AL and
      postoperative morbidity in general will be evaluated using the appropriate
      univariate and multivariate statistical analyses. DISCUSSION: The results of this
      project may lead to a novel, reproducible, and minimally invasive method to
      objectively assess perioperative anastomotic perfusion during MIE, potentially
      reducing the incidence of AL and its associated severe morbidity and mortality.
      TRIAL REGISTRATION: Clinicaltrials.gov registration number is NCT03587532. The
      study was approved by the ethical committee of the Ghent University, Belgium
      (B670201836427).

PMID- 30235662
TI  - Expression of Tim-3 in peripheral blood mononuclear cells and placental tissue in
      unexplained recurrent spontaneous abortion.
AB  - The expression of T-cell immunoglobulin domain, mucin domain-3 (Tim-3) in
      unexplained recurrent spontaneous abortion (URSA) was investigated.Tim-3 mRNA
      expression in peripheral blood mononuclear cells (PBMCs) of URSA and control
      groups was assayed by fluorescent quantitative real-time polymerase chain
      reaction. Tim-3 protein expression intensity and localization in placental villi
      and uterine decidua were determined using immunohistochemical assay. The CD4Tim
      3/CD4 cell ratio in PBMCs was determined by flow cytometry.Tim-3 mRNA expression
      in PBMCs was significantly higher in URSA than in normal controls (1.32 +/- 0.25
      vs 1.20 +/- 0.12, P < .05). Tim-3 was expressed in placental tissue from both
      URSA patients and normal pregnant females (controls); however, the expression
      intensity was higher in the URSA group (0.54 +/- 0.31 vs 0.35 +/- 0.22, P < .05).
      CD4Tim-3/CD4 cell ratio in PBMCs was significantly higher in the URSA group than
      that in the control group (4.53 +/- 1.66% vs 1.28 +/- 0.71%, P < .05).Increased
      Tim-3 expression in PBMCs and placental tissue of URSA might affect maternal
      fetal immune tolerance. Tim-3 was involved in the pathogenesis of URSA, which was
      expected to serve as an indicator for the immune evaluation of URSA.

PMID- 30235665
TI  - Urinary tract infection control in intensive care patients.
AB  - This retrospective study tried to find the potential approach for reducing the
      urinary tract infection (UTI) in intensive care patients (ICPs) among adult
      population.In total, 96 eligible ICP cases were included. Of these, 48 cases
      received 10% povidone-iodine and were assigned to the intervention group, while
      the other 48 cases underwent sterile water, and were assigned to the control
      group for the prevention of catheter-associated UTI before indwelling urinary
      catheter insertion in ICP. The primary outcome was the occurrence of an UTI after
      the indwelling catheter. The secondary outcome was the identification of
      pathogenic species. The outcomes were assessed after catheter removed.After
      catheter removal, the occurrence of an UTI did not differ significantly between
      the 2 groups (P = .34). In addition, no significant differences regarding the
      pathogenic species were detected between the 2 groups (Escherichia coli, P = .73;
      Candida albicans, P = .57; Enterococcus, P = .65; Proteus mirabilis, P = .50;
      Citrobacter, P = .50; Klebsiella pneumoniae, P = .57).The use of 10% povidone
      iodine may not help reducing UTI in ICP.

PMID- 30235663
TI  - Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic
      diagnosis and treatment: A Digestive Endoscopy Society of Tawian (DEST).
AB  - Gastric neuroendocrine tumors (GNETs) are a heterogeneous group of neoplasm with
      varying biological characteristics. This study aimed to investigate the clinical
      features and outcomes of GNET patients after endoscopic diagnosis and treatment
      in a multicenter registry. Patients with GNETs confirmed histologically were
      recruited from 17 hospitals between January 2010 and April 2016 in Taiwan.
      Clinical, laboratory, radiological, endoscopic, pathological data, treatment
      strategies, follow-up periods, and survivals were collected retrospectively.
      Totally 187 (107 female, 80 male) patients were recruited. Mean ( +/- standard
      deviation [SD]) age and size of tumors were 63.2-year-old ( +/- 14.6) and 2.3-cm
      ( +/- 3.0). World Health Organization (WHO) grading were 93 (49.7%) G1, 26
      (13.9%) G2, 40 (21.4%) G3, and 28 (15.0%) unknown. G3 patients were older (mean
      +/- SD, 71.6 +/- 12.4 vs. 60.9 +/- 14.3/56.7 +/- 15.4 years), larger (6.1 +/- 4.0
      vs.1.2 +/- 1.3/2.4 +/- 2.5 cm), more distally located (35.0% vs. 7.6%/15.4%),
      lower proportion of superficial lesions (17.5% vs. 61.9%/53.8%) and higher rates
      of lymphovascular invasion (32.5% vs. 3.2%/7.7%) than G1/G2. There was no nodal
      or distant organ metastases despite different grading of lesions?10 mm and those
      <20 mm limited to mucosa and submucosa layers. GNETs larger than 20 mm with G1,
      G2, and G3 had lymph node (LN) metastatic rates of 21.4%, 30.0%, and 59.3%,
      respectively. Survivals were different between grading for those >20 mm (log-rank
      test P = .02). Male gender (P = .01), deeper invasion (P = .0001), nodal (P <
      .0001), and distant organ metastases (P = .0001) were associated with worse
      outcome. In conclusion, treatment strategies for GNET should be decided by
      grading, size, invasiveness, and LN metastasis risk. Curative endoscopic
      resection is feasible for G1/2 lesions less than 20 mm and limited to
      mucosa/submucosa layers without lymphovascular invasion.

PMID- 30235664
TI  - Ambulatory blood pressure monitoring and diabetes complications: Targeting
      morning blood pressure surge and nocturnal dipping.
AB  - Ambulatory blood pressure monitoring (ABPM) correlates more closely to organ
      damages than clinic blood pressure (BP). In the current study we aimed to
      investigate the association between micro- and macrovascular complications of
      diabetes and both diurnal and nocturnal variability in BP.A total of 192 patients
      with type 2 diabetes (T2DM) who had complete data on ABPM were selected. BP
      categories were defined based on 2017 ACC/American Heart Association BP
      guideline. The cross-sectional association between different BP phenotypes and
      diabetes complications including cardiovascular disease (CVD), nephropathy,
      retinopathy, and neuropathy was assessed using multiple logistic regression
      models adjusted for age, sex, body mass index, hypertension (HTN), hemoglobin
      A1c, fasting blood glucose (FBG), triglyceride (TG), high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, and total
      cholesterol.Approximately 48.9% of participants with T2DM had 24-hour HTN. The
      prevalence of daytime, nighttime, and clinic HTN were 35.9%, 96.3%, and 53.1%,
      respectively. Approximately 54.2% of participants had nondipping nocturnal
      pattern and 28.6% were risers. Nondipping nocturnal BP was associated with CVD,
      neuropathy, and retinopathy (P = .05, .05, and .014, respectively). Sleep trough
      morning blood pressure surge (MBPS) was associated with neuropathy (P = .023).
      Neuropathy was also associated with other components of MBPS (P < .05).We
      demonstrated that diabetic neuropathy was associated with all the components of
      MBPS and abnormal dipping status. Our results indicated loss of nocturnal BP
      dipping but not MBPS as a risk factor for CVD and retinopathy in patients with
      T2DM. Our findings once again highlighted the importance of ambulatory BP
      monitoring and targeted antihypertensive therapy directed toward to restore
      normal circadian BP in patients with T2DM.

PMID- 30235666
TI  - An epidemiological survey of HBV infection and low-level HBsAg in military camps
      in eastern China.
AB  - This study aimed to investigate hepatitis B virus (HBV) infection in military
      personnel in eastern China, which will provide a basis for the prevention of HBV
      infection.A total of 15,508 soldiers and 2386 officers were recruited from
      military camps in eastern China. The markers, deoxyribonucleic acid, serotypes,
      and genotypes of HBV in serum were detected and analyzed.Hepatitis B surface
      antigen (HBsAg) positive rate was 0.44% in soldiers, in whom the low-level HBsAg
      accounted for 88.24%. The HBsAg positive rate was 1.72% in officers in whom the
      low-level HBsAg accounted for 12.20%. There were significant differences in the
      prevalence of high-level and low-level HBsAg, HBV serotypes, HBV DNA positive
      rate, and mean log HBV DNA between officers and soldiers (P < .05). Compared with
      the conventional method for HBV DNA extraction, the enrichment method for HBV DNA
      extraction could significantly improve the positive rate and quantification of
      HBV DNA by real-time fluorescence quantitative polymerase chain reaction (P <
      .05). Sequencing of S gene in HBV was used for the determination of serotype and
      genotype of HBV. The sequencing success rate was significantly different between
      soldiers and officers (P < .05) as well as between high-level HBsAg group and low
      level HBsAg group (P < .05). Significant difference was also observed in the
      genotype distribution between soldiers and officers (P < .05).HBV infection
      displays a low prevalence and a low epidemic state, and the prevalence of low
      level HBsAg is higher in soldiers. We should pay attention to improve the quality
      of conscription examination as well as emphasize the surveillance, prevention,
      and protection of HBV infection in military officers.

PMID- 30235667
TI  - Genetic polymorphisms of pharmacogenomic VIP variants in the Lisu population of
      southwestern China: A cohort study.
AB  - Pharmacogenomic studies of different ethnic or racial groups have been used to
      develop personalized therapies specific to subjects. This study aimed to identify
      the distribution differences of very important pharmacogenetic (VIP) variants
      between the Lisu population from southwestern China and other ethnic
      groups.Eighty VIP variants in 37 genes were selected from the pharmacogenomic
      knowledge base (PharmGKB), and compared with genotype data of the Lisu population
      then compared with other 11 populations from the HapMap dataset and previously
      published data including Miao, Li, Deng, Sherpa, Lhoba, Tibetan, Kirghiz, Tajik,
      Mongol, Shaanxi Han ethnic, and Uygur populations.VDR rs1540339, MTHFR rs1801131,
      P2RY1 rs701265, and PTGS2 rs689466 were significantly different between Lisu and
      11 HapMap populations. ANKK1 rs1800497 was the least statistical significant
      locus among selected single nucleotide polymorphisms. In addition, genetic
      background of Lisu was strongly closest to Shaanxi Han ethnic cohort, and
      followed by Chinese in metropolitan Denver population based on population
      structure and F-statistics analyses.Our results showed significant interethnic
      differences between Lisu and other populations, which will give useful
      information for prospective studies and better individualized treatments.

PMID- 30235669
TI  - A rare development of basal cell carcinoma on trichoepithelioma in a chemical
      burn scar tissue: A case report.
AB  - RATIONALE: Trichoepithelioma (TE) is a rare benign skin tumor that originates
      from the hair follicle epithelium. Although skin lesions arising from scar
      tissues are mostly malignant, the development of a benign tumor such as TE is a
      rare event. PATIENT CONCERNS: A 28-year-old male patient who had a scar on the
      left cheek which arose 10 years ago because of a chemical burn visited our
      hospital. Scar revision was performed under local anesthesia. DIAGNOSIS:
      Histological examination identified the specimen as a TE with malignant foci
      suspicious of basal cell carcinoma (BCC) at the lateral margin of the specimen.
      INTERVENTIONS: A second stage operation was planned to excise the BCC with a 4 mm
      margin of the normal skin around the previous lesion. OUTCOMES: No complication
      or recurrence was noted during the 1-year follow-up period after surgery, and the
      appearance of the scar improved. LESSONS: The correct differential diagnosis
      between TE and BCC is very important. So follow up at regular intervals is
      recommended for evaluation of recurrence or transformation into BCC in patients
      with tumors arising from chemical burn scars. And the concomitant development of
      TE and BCC should also be considered from a chemical burn scar.

PMID- 30235670
TI  - Meta-analysis of correlationship between HLA-G 3'UTR 14-bp Ins/Del polymorphism
      and virus susceptibility.
AB  - BACKGROUND: There is a considerable amount of literature on the potential
      relationship between human leukocyte antigen-G 14-bp Ins/Del polymorphism and
      virus infection; however, results from these studies were inconclusive.
      OBJECTIVES: A meta-analysis was carried out to determine whether the 14-bp
      Ins/Del polymorphism is a susceptible factor for virus infection. METHODS: Data
      were extracted from PubMed and Web of Science databases, and included 10 case
      control studies (1835 patients and 2357 controls). RESULTS: A total of 177
      records from 10 studies were retrieved. Overall, no significant correlation was
      found between HLA-G 14-bp Ins/Del polymorphism and total viruses under all
      genetic models (dominant model: OR = 0.93, 95% CI = 0.68-1.29; recessive model:
      OR = 1.12, 95% CI = 0.84-1.48; deletion/deletion (DD) vs insertion/insertion
      (II): OR = 1.03, 95% CI = 0.71-1.49; deletion (D) vs insertion (I): OR = 1.01,
      95% CI = 0.81-1.25). However, further subgroup analyses by virus type and
      ethnicity revealed that HLA-G 14-bp Ins/Del polymorphism was significantly
      associated with HTLV-1 infection in mixed population under the dominant model.
      CONCLUSIONS: Our study demonstrated that HLA-G 14-bp Ins/Del polymorphism may not
      have any effect on susceptibility to viruses.

PMID- 30235668
TI  - Impact of co-infection by hepatitis C virus on immunological and virological
      response to antiretroviral therapy in HIV-positive patients.
AB  - We assessed the effect of co-infection by hepatitis C virus (HCV) on
      immunological and virological response at 48 weeks from initiation of
      antiretroviral therapy (ART).We included patients from the Cohort of Spanish HIV
      Research Network (CoRIS) starting ART between January 2004 and November 2014, had
      at least 1 CD4 T-cell count and viral load measurements both in the previous 6
      months and at 48 (+/-12) weeks from ART initiation, and HCV serology before ART
      initiation. We used linear regression for mean differences in CD4 T-cell count
      increase from ART initiation and logistic regression to estimate odds ratios for
      virological response.Of 12,239 patients by November 30, 2015, 5070 met inclusion
      criteria: 4382 (86.4%) HIV mono-infected and 688 (13.6%) HIV/HCV co-infected. Co
      infected patients were more likely to have acquired HIV through injecting drugs
      use (57.4% vs. 1.1%), to be women, older, and Spanish, have a lower educational
      level, and having started ART with lower CD4 counts and acquired immunodeficiency
      syndrome. CD4 T-cell count increase at 48 weeks was 229.7 cell/MUL in HIV
      monoinfected and 161.9 cell/MUL in HIV/HCV-coinfected patients. The percentages
      of patients achieving a virological response at 48 weeks were 87.0% and 78.3% in
      mono and coinfected patients, respectively. Multivariable analyses showed that at
      48 weeks, coinfected patients increased 44.5 (95% confidence interval [CI]: 24.8
      64.3) cells/MUL less than monoinfected and had lower probability of virological
      response (odds ratio: 0.62; 95% CI: 0.44-0.88).HIV/HCV-coinfected patients have
      lower immunological and virological responses at 48 weeks from ART initiation
      than monoinfected patients.

PMID- 30235671
TI  - The association of adverse outcomes in the mother with disease progression in
      offspring in families with clusters of hepatitis B virus infection and
      unfavorable prognoses in Northwest China.
AB  - To investigate the transmission routes of hepatitis B virus (HBV) in families
      with clusters of infection and unfavorable prognoses and to analyze the
      prevalence of liver cirrhosis (LC) or hepatocellular carcinoma (HCC) in the
      offspring of these families.Families with clusters of HBV infection and
      unfavorable prognoses were enrolled in the study, and general information and
      serum samples were collected. The prevalence of LC or HCC was compared in
      offspring of different genders whose parents were diagnosed with LC or HCC.This
      analysis comprised 102 probands with 51 siblings, 15 parents, 284 children, and
      74 spouses. Interestingly, 88.2% of the siblings and 76.8% of the children of
      these probands were positive for hepatitis B surface antigen (HBsAg), compared
      with only 9.5% of the spouses (P < .001). There were 266 nuclear families from
      102 clustering families. The prevalence of LC or HCC in sons (44.8%) was higher
      than that in daughters (8.2%; P < .05) in families with mothers with LC or HCC,
      but there was no difference in families with fathers with LC or HCC. Moreover,
      the prevalence of LC or HCC in sons from families with mothers with LC or HCC
      (44.8%) was higher than in the families with fathers with LC or HCC (21.0%, P =
      .016).The development of LC or HCC in offspring showed a greater relationship
      with the adverse outcomes induced by HBV infection in the mother compared with
      the father, and the prevalence of LC or HCC was much higher in male offspring.

PMID- 30235672
TI  - Unusual variant of distal biceps femoris muscle associated with common peroneal
      entrapment neuropathy: A cadaveric case report.
AB  - RATIONALE: The anatomical variant of the distal biceps femoris muscle with regard
      to common peroneal nerve entrapment neuropathy (CPNe) was suggested through
      magnetic resonance images (MRI) study. PATIENT CONCERNS: An unusual variant of
      distal biceps femoris muscle was observed in 78 years old male cadaver.
      DIAGNOSES: The short head of biceps femoris muscle (SHBFM) was extended more
      distal and posteriorly. INTERVENTION: The popliteal area was dissected at knee
      joint level in a cadaveric limb. OUTCOMES: Common peroeal nerve (CPN) was
      situated within tunnel formed between the lateral head of the gastrocnemius
      muscle (LGCM) and the SHBFM. Also, the length of tunnel was 4.4 cm. LESSONS: The
      case illustrated here, to the best of our knowledge, is the first one with
      cadaveric findings of variant of distal biceps femoris muscle associated with
      CPNe. The tunnel formed between the more posterior or distal extension of the
      SHBFM and the LGCM could be possible entrapment area of CPN, clinically.

PMID- 30235674
TI  - Castleman disease mimicking systemic lupus erythematosus: A case report.
AB  - RATIONALE: Castleman disease (CD) is a nonclonal lymphoproliferative disorder
      sometimes manifested systemic inflammatory symptoms. Systemic lupus erythematosus
      (SLE) is an autoimmune disease characterized with multi-system involvement as
      well as broad spectrum of serum autoantibodies. When these two conditions
      happened to have similar clinical spectrum features, the confusion with each
      other occurred. PATIENT CONCERNS: A 46-year-old man suffered from chronic fever,
      nephrotic syndrome, acute kidney injury, anemia, thrombocytopenia and serositis,
      as well as hypocomplementemia and negative anti-nuclear antibody. DIAGNOSES:
      Meeting the classification criteria for SLE, the patient was diagnosed as SLE at
      first. The renal biopsy showed that he had endocapillary proliferative
      glomerulonephritis with negative immunofluorescence. Finally, he was diagnosed
      with CD after lymph nodes biopsy. INTERVENTIONS: The patient was treated with
      oral prednisone (50 mg daily) but got poor response. After being proved to have
      CD, he was treated with CHOP chemotherapy. OUTCOMES: His condition was controlled
      by CHOP chemotherapy. After six course of chemotherapy, the proteinuria
      disappeared. LESSONS: If patients, even qualified by classification criteria of
      SLE, had negative autoantibody or unsatisfied response to the standard treatment,
      the original diagnosis should be suspected. The biopsy may be help to identify
      the final criminals, such as CD.

PMID- 30235673
TI  - Analysis of mutation spectrum of common deafness-causing genes in Hakka newborns
      in southern China by semiconductor sequencing.
AB  - Hearing loss is a common neurosensory disorder, approximately half of the cases
      are caused by genetic factors, and approximately 70% of hereditary hearing
      impairments are nonsyndromic hearing loss (NSHL). The mutations of GJB2 (gap
      junction beta-2 protein), GJB3 (gap junction beta-3 protein), SLC26A4 (solute
      carrier family 26 member 4), and MT-RNR1 (mitochondrially encoded 12S RNA) are
      the most common inherited causes of NSHL. Because of different genetic
      backgrounds, the mutation spectrum of these common deafness-causing genes varies
      among different regions in China. Because no data are known on these mutations
      among the Hakka population of Southern China, we aim to investigate the mutation
      spectrum to add these to neonatal screening and genetic counseling. A total of
      1252 blood samples from newborns have been detected by semiconductor sequencing
      for 100 mutations loci of 18 deafness-causing genes. Of the participants, 95
      subjects carried deafness-causing genes mutations with the carrier rate of 7.59%.
      The mutation frequencies of GJB2, SLC26A4, GJB3, and mitochondrial genes were
      3.04%, 3.51%, 0.16%, and 0.88%, respectively. We followed up subjects with single
      gene homozygous or compound heterozygous mutations. Our study firstly analyzed
      deafness-causing genes mutation spectrum in Hakka population, providing evidence
      for future neonatal screening and genetic counseling in this area.

PMID- 30235675
TI  - Adenoma miss rate determined by very shortly repeated colonoscopy: Retrospective
      analysis of data from a single tertiary medical center in China.
AB  - Adenoma miss rate (AMR) has been calculated in several tandem colonoscopy
      studies, but it costs overmuch to carry out a clinical trial.We aimed to put
      forward AMR by taking advantage of retrospective data, and to judge the
      comparability between AMRs from prospective and retrospective data.Data of the
      patients accepting repeated colonoscopies during January to September 2016 was
      retrospectively collected and analyzed. Information was recorded, including bowel
      preparation quality of the first colonoscopy, size, location, histology and
      whether missed within the first colonoscopy of each single adenoma. AMR was
      compared by different risk factors through chi test and multivariable logistic
      regression.Around 267 adenomas were detected during 309 pairs of repeated
      colonoscopies, of which 66 were missed during the first colonoscopies. AMRs of
      the lesions small in size, nonadvanced in histology, in poor bowel preparation
      context and located in the proximal colon, were significantly higher than the
      opposite ones, and old age and male were related to adenoma missing (P < .05). In
      multivariable logistic regression analysis, adenoma-related factors (diminutive
      in size, poor bowel preparation and located in ascending colon, transverse colon
      or sigmoid colon), and patient-related factors (older than 60 years, male and
      poor bowel preparation) were found to be independently associated with missing
      adenomas (P < .05).AMR of retrospective data is comparable to that of tandem
      studies. Several risk factors influence AMR dramatically, which should be paid
      attention to.

PMID- 30235676
TI  - Effectiveness of neuromuscular electrical stimulation for wrist rehabilitation
      after acute ischemic stroke.
AB  - This study investigated the effectiveness of neuromuscular electrical stimulation
      (NMES) for patients with wrist dysfunction after acute ischemic stroke (AIS).A
      total of 82 patient cases with wrist dysfunction after AIS were selected in this
      study. Of these, 41 cases in the intervention group received physical training
      and NMES treatment. The other 41 cases in the control group received physical
      training only. The primary outcome was measured by Action Research Arm Test
      (ARAT) score. The secondary outcomes were measured by the Barthel Index (BI), and
      numerical rating scale (NRS).After 4-week treatment, patients in the intervention
      group neither improved arm function recovery, measured by ARAT score (P = .79),
      and activities of daily living, measured by BI scale (P = .62), nor reduced pain,
      measured by the NRS scale (P = .11), compared with patients in the control
      group.The results of this study demonstrated that NMES might not benefit for
      patients with wrist dysfunction after AIS after 4-week treatment.

PMID- 30235677
TI  - Concomitant p53 and PTEN immunoexpression to predict the risk of malignancy in
      endometrial polyps.
AB  - The aim of this retrospective cross-sectional study was to assess the usefulness
      of phosphase and tensin homolog deleted on chromosome 10 (PTEN) and p53 protein
      immunoexpression in predicting the risk of malignancy in endometrial polyps. The
      study was conducted at tertiary public hospital, university teaching center, and
      private practice clinic.A total of 159 patients with endometrial polyps who
      underwent hysteroscopic polypectomy between January 2010 to December 2014 were
      included. p53 and PTEN immunoexpression were assessed in histologic endometrial
      polyp samples. Patients were allocated into 2 groups: group A, endometrial polyps
      without atypia (120), and group B, endometrial polyps with atypia (39), which
      were subdivided into A1 (80) and B1 (21) = p53-/PTEN+ immunostaining; A2 (20) and
      B2 (11) = p53+/PTEN+; A3 (14) and B3 (4) = p53+/PTEN-; A4 (6) and B4 (3) = p53
      /PTEN-.There was no significant difference between groups regarding clinical and
      epidemiologic parameters, except for age. Neoplasia incidence within groups was
      higher when at least 1 marker was abnormally stained (in group A, P = .0089, odds
      ratio [OR] = 13.94 [1.62; 120.27]; in group B, P = .0255, OR 12.73 [1.38;
      117.27]). Overall neoplasia incidence was higher in group B than in group A
      (20.5% vs 5.8%; P = .0113). Malignant neoplasia was found more frequently in
      patients with p53+ (P = .0006, OR = 7.67 [2.30; 25.54]) and PTEN- (P = .0043; OR
      = 5.43 [1.77; 16.61]).Immunohistochemical analysis using p53 and PTEN as markers,
      either alone or concomitantly, can be useful to predict malignant transformation
      in cases of endometrial polyps.

PMID- 30235679
TI  - Dasatinib monotherapy for newly diagnosed Philadelphia chromosome-positive acute
      lymphoblastic leukemia with pulmonary infection in induction remission: A case
      report and review of the literature.
AB  - RATIONALE: There is currently no clinical standard for induction therapy in the
      treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph
      ALL). Chemotherapy in combination with tyrosine kinase inhibitors (TKIs)
      recognized as the first line of therapy to induce remission in Ph ALL patients;
      however, both the infectious and non-infectious toxicities remain high and lead
      to early excessive treatment-related mortality (TRM). Single-agent TKI
      "monotherapy" may reduce toxicity and TRM; however, TKI induction monotherapy and
      its effectiveness in the induction of remission in newly diagnosed Ph ALL has yet
      to be investigated. PATIENT CONCERNS: A 59-year-old man who was newly diagnosed
      Ph ALL with 93% blast cells and a t (9, 22) karyotype. But the patient also
      suffered from pulmonary infection, including fever and dyspnea. DIAGNOSES: The
      patient was newly diagnosed with Ph ALL with pulmonary infection. INTERVENTIONS:
      The patient received oral dasatinib monotherapy (100 mg qd) for 28 days as
      induction therapy. OUTCOMES: The patient reached complete remission with negative
      minimal residual disease detected by real-time quantitative polymerase chain
      reaction after induction therapy for 28 days. LESSONS: This is the first report
      on the use of dasatinib monotherapy in the absence of other drugs, such as
      steroids, for induction therapy in a newly diagnosed Ph ALL patient with
      pulmonary infection.

PMID- 30235680
TI  - Mobile health, physical activity, and obesity: Subanalysis of a randomized
      controlled trial.
AB  - BACKGROUND: Recent studies on physical activity were analyzed by randomizing
      participants into either the intervention or control group. It is necessary to
      classify each intervention and control groups according to physical activity
      using the International Physical Activity Questionnaire (IPAQ). METHODS: This was
      a pilot project for SmartCare Services. The intervention group received obesity
      management services using a smartphone for 24 weeks, while the control group did
      not receive the interventions. Six anthropometric indices were analyzed: weight,
      body mass index (BMI), waist circumference, body fat, systolic blood pressure
      (SBP), and diastolic blood pressure (DBP). Five laboratory tests, including
      fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), high-density
      lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TGs),
      were also assessed. The final 324 participants were categorized using the IPAQ
      questionnaire, and anthropometric indices and laboratory tests were analyzed for
      within-group and between-group changes from baseline to final visit. RESULTS:
      Statistically significant decreases in the intervention group compared with the
      control group were observed in terms of insufficient activity (IA) (-1.6 +/- 3.03
      vs -0.1 +/- 1.94 kg) and moderate activity (MA) (-2.5 +/- 3.81 vs -0.3 +/- 2.24
      kg) for weight, IA (-0.7 +/- 1.14 vs -0.2 +/- 0.93 kg/m) and MA (-0.9 +/- 1.30 vs
      -0.2 +/- 0.86 kg/m) for BMI, and health-enhancing physical activity (HEPA) (-1.6
      +/- 3.69% vs -0.1 +/- 3.15%) for body fat. For HbA1c, HEPA in the intervention
      group showed significant decreases (-0.2 +/- 0.67 vs 0.0 +/- 0.34 mg/dL) compared
      with the control group. CONCLUSION: Anthropometric indices and laboratory test
      results were improved in the smartphone-based intervention group. Especially,
      improvement of metabolic components in the group with more active physical
      activity was remarkable.

PMID- 30235678
TI  - Subclinical inflammation in a case of menstruation-induced familial Mediterranean
      fever: A case report.
AB  - RATIONALE: Because most patients with familial Mediterranean fever (FMF) have
      attacks without any prodromal symptoms, and since it is suggested that patients
      with FMF have subclinical inflammation even during remission, a daily continuous
      administration of colchicine is recommended for patients with FMF even during
      remission. However, it is possible that intermittent colchicine therapy only
      during FMF attacks prevents the attacks completely in patients with FMF with
      expectable attacks. PATIENT CONCERNS: A 31-year-old Japanese woman suffered high
      fever and arthralgia lasting for 2 to 3 days after each menstrual period's start.
      She was admitted to our hospital, and colchicine was administered immediately
      after her next period's start, and the febrile attack was completely prevented.
      DIAGNOSES: We eventually diagnosed typical FMF. INTERVENTIONS: Her remission has
      been maintained by intermittent colchicine therapy. OUTCOMES: The genetic
      analysis revealed the G304R heterozygous mutation in exon 2 of the MEFV gene.
      Cytokine analysis suggested subclinical inflammation during the remission period.
      LESSONS: This case suggests that taking an extensive medical history (including
      the relationship between fever attack and menstruation) is important in the
      diagnosis of female patients with FMF. This case also suggests that a continuous
      administration of colchicine may have to be considered to regulate subclinical
      inflammation even in patients with FMF with completely expectable attacks.

PMID- 30235681
TI  - Neonate female to male ratio after assisted reproduction following antagonist and
      agonist protocols.
AB  - We retrospectively compared neonatal sex after antagonist- versus long
      stimulation protocols followed by fresh in vitro fertilization (IVF) or fresh
      intracytoplasmic sperm injection (ICSI) with either protocol. We reviewed data
      for 762 IVF/ICSI cycles in 2015, including 23 IVF procedures. We summarized sex
      outcomes in the entire cohort, and for the additional subgroups: embryo transfer
      day and number of embryos transferred, and number of oocytes recovered and
      maternal age. Among 169 live births for all protocols combined, 50.9% of babies
      were male, and we saw no difference between the antagonist versus long
      stimulation groups (52.3% vs 48.3% male babies, respectively; P = .740). Our
      results also showed no significant difference in sex proportion when comparing
      IVF versus ICSI, although a higher proportion of babies were male with the
      antagonist-ICSI protocol. Differences between the additional subgroups were also
      neither clinically nor statistically significant.

PMID- 30235683
TI  - Atypical onset of total colonic Hirschsprung disease in a small female infant: A
      case report.
AB  - RATIONALE: Hirschsprung disease (HD) or colonic aganglionosis is a congenital
      disorder, which results from the abnormal migration of neuronal cells of the
      neural crest leading to a disorder of the enteric nervous system consisting in
      the absence of ganglion cells within the submucosal and myenteric plexus. PATIENT
      CONCERNS: We report the case of a 7-month-old female infant admitted in our
      clinic for constipation and failure to thrive. At the age of 6 months, she was
      examined in our clinic for the same reasons, and we recommended symptomatic
      treatment without improvements. The clinical examination revealed pallor of the
      skin and mucosa, distended abdomen, and abdominal tenderness at palpation.
      DIAGNOSES: The abdominal ultrasound showed abdominal bloating, and the barium
      enema was normal. The patient's evolution worsened progressively within the
      following 3 days after admission associating sings of toxic megacolon.
      INTERVENTIONS: She underwent a surgical intervention with total colectomy and
      ileostomy, and the final diagnosis confirmed by the histological examination was
      of total colonic aganglionosis (TCA). OUTCOMES: The evolution immediately after
      the surgery and the follow-up examination after approximately 3 months pointed
      out normal weight gain and the laboratory tests were within normal limits.
      LESSONS: TCA can also manifest in older infants. Barium enemas can guide the
      diagnosis in most cases of HD. Nevertheless, in patients with TCA, it can be
      normal. Moreover, it could represent a trigger for toxic megacolon.

PMID- 30235682
TI  - New endemic familial parkinsonism in south Moravia, Czech Republic and its
      genetical background.
AB  - An increased prevalence of familial neurodegenerative parkinsonism or cognitive
      deterioration was recently found in a small region of southeastern Moravia.The
      aim of the study was to assess the genetic background of this familial
      disease.Variants in the ADH1C, EIF4G1, FBXO7, GBA + GBAP1, GIGYF2, HTRA2, LRRK2,
      MAPT, PRKN, DJ-1, PINK1, PLA2G6, SNCA, UCHL1, VPS35 genes were examined in 12
      clinically positive probands of the pedigree in which familial atypical
      neurodegenerative parkinsonism was identified in previous epidemiological
      studies. Libraries were sequenced by massive parallel sequencing (MPS) on the
      Personal Genome Machine (PGM; Ion Torrent). Data were analyzed using Torrent
      Suite and IonReporter software. All variants were then verified and confirmed by
      Sanger sequencing.We identified 31 rare heterozygous variants: 11 missense
      variants, 3 synonymous variants, 8 variants in the UTR region, and 9 intronic
      variants. Six variants (rs1801334, rs33995883, rs35507033, rs781737269,
      rs779760087, and rs63750072) were evaluated as pathogenic by at least one in
      silico predictor.No single "founder" pathogenic variant associated with
      parkinsonism has been found in any of the probands from researched pedigree. It
      may rather be assumed that the familial occurrence of this disease is caused by
      the combined influence of several "small-effect" genetic variants that accumulate
      in the population with long-lasting inbreeding behavior.

PMID- 30235684
TI  - Novel electronic health record (EHR) education intervention in large healthcare
      organization improves quality, efficiency, time, and impact on burnout.
AB  - A novel approach to advanced electronic health record (EHR) skills training was
      developed in a large healthcare organization to improve high-quality EHR
      documentation, while reducing stressors linked to physician burnout.The 3-day
      intensive EHR education intervention covered best practices in EHR documentation
      and physician well-being. The specialty physician faculty used interactive
      teaching including demonstration, facilitation, and individual coaching. Laptops
      were provided for hands-on practice. Mixed-method evaluation included real-time
      feedback, daily surveys, and post-activity surveys to measure participant
      learning and satisfaction, and also collection of performance data from the EHR
      to measure use of order sets designed to improve quality of care.Since 2014, 46
      trainings were held with 3500 physicians. Most physicians (85%-98% across all
      programs) reported improved quality, readability, and clinical accuracy of
      documentation; fewer medical errors; and increased efficiency in chart review and
      data retrieval due to the training. Seventy-eight per cent estimated a time
      savings of 4 to 5 minutes or more per hour. Physician performance data from the
      EHR showed significant improvement in use of order sets for several critical
      health conditions such as sepsis, stroke, and chest pain of possible cardiac
      cause.This advanced EHR training for physicians was well-received and improved
      physicians' use of several order sets designed to improve quality of care. EHR
      training programs such as this may have impact on the safety, quality, accuracy,
      and timeliness of care and may also help reduce physician burnout by improving
      critical skills and reducing time interfacing with all aspects of a patient's
      health record.

PMID- 30235686
TI  - Etiology and clinical manifestations of bacterial liver abscess: A study of 102
      cases.
AB  - This study aimed to analyze the clinical manifestations of patients with pyogenic
      liver abscess and characteristics of pathogenic that caused their infections, in
      order to provide guidance for the identification of the pathogens that cause
      liver abscess and selection of antibiotics for treatment of this disease.In the
      present study, the clinical characteristics, laboratory results, as well as the
      species and drug resistance of pathogens in patients with bacterial liver
      abscesses admitted to our hospital from January 2013 to December 2015 were
      retrospectively analyzed. The patients were treated by ultrasound or CT-guided
      percutaneous portal vein catheterization and drainage combined with intravenous
      infusion of antibiotics (the third-generation cephalosporins, the coformulation
      of carbapenem and dehydropeptidase-I inhibitors, or the coformulation of
      tazobactam and piperacillin).A total of 178 patients were diagnosed with liver
      abscess by B ultrasound or CT. The abscesses mostly occurred in elderly male
      patients and patients with diabetes mellitus. The major clinical and
      hematological features were fever (163/178, 91.2%), single focal abscess
      (146/178, 82.0%), elevated white blood cell count, and percentage of neutrophils
      (136/178, 76.4%). A total of 102 nonrepetitive strains of bacteria were isolated,
      including Klebsiella pneumoniae (82 strains, 80.3%), Escherichia coli (8
      strains), Pseudomonas aeruginosa (2 strains), Acinetobacter baumannii (1 strain),
      and Gram-positive cocci (9 strains). Susceptibility to antimicrobial drugs was
      determined by analyzing the minimum inhibitory concentration, and among the 8
      cultured E coli strains, 5 strains that could produce extended-spectrum beta
      lactamase (ESBLs) were among the most commonly seen nosocomial infections. In the
      present study, bacterial liver abscesses were mostly community-acquired, and K
      pneumoniae was highly susceptive to the commonly used antibiotics. Five patients
      had poor outcomes due to infectious shock or the accompanying liver cancer. In
      other patients, after treatment, the body temperature and the inflammatory
      indices, such as the total white blood cell count and C-reactive protein,
      returned to normal levels, and the area of abscess decreased.Most of the
      bacterial liver abscesses were caused by K pneumoniae, in which only a few
      strains exhibited resistance to the commonly used antibiotics. The use of
      ultrasound- or CT-guided percutaneous drainage combined with antibiotics was an
      appropriate way to treat the liver abscesses of these patients.

PMID- 30235685
TI  - The effect of Three-Circle Post Standing (Zhanzhuang) Qigong on the physical and
      psychological well-being of college students: Study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: The physical and mental health of college students tends to
      continuously decline around the world due to lifestyle or behavior habits
      changes, and pervasive presence of the Internet. Thus it is urgent to improve
      their health in college life. As a traditional Qigong form is practiced mainly in
      a standing posture. Three-Circle Post Standing Qigong (TCPSQ) is suitable for
      regular practicing and has beneficial effects on improving the physiological
      function and psychological emotion by adjusting body, breathing, and mind. The
      aim of the 3 adjustments is to achieve a state of harmonious unity-integrating
      these adjustments into "one." In this study protocol article, we will
      systematically explore the effectiveness and safety, feasibility of TCPSQ on
      physical and psychological outcomes of the college students and deeply understand
      the state of harmonious unity-integrating adjustments of body, breath, and mind
      into "one." METHOD/DESIGN: We will conduct a randomized, assessor, and
      statistician blinded, parallel-controlled trial comparing the beneficial effect
      of TCPSQ in college students. A total of 80 eligible college students from the
      Beijing University of Chinese Medicine (BUCM) will be recruited and randomly
      allocated into TCPSQ training or unaltered lifestyle control group according 1:1
      allocation ratio with allocation concealment. TCPSQ intervention will last 10
      weeks. The study period is 18 weeks including a 10-week supervised intervention
      and a 8-week follow-up. The relevant physical and psychological outcomes, adverse
      events, and safety will be evaluated at baseline, 6 weeks (at the mid-point of
      intervention), 11 weeks (at the end of intervention), and 19 weeks (after the 8
      week follow-up period) by blinded independent outcome assessors. DISCUSSION: This
      is the first randomized controlled trial protocol from the perspective of Qigong
      connotation to systematically investigate the effect of TCPSQ for the physical
      and mental health of a college student population. If the results in our study
      prove a significant intervention effect, this would provide preliminary higher
      quality evidence and establish an optimal guidance for the application of TCPSQ
      exercise program among a college student population. ETHICS AND DISSEMINATION:
      The study was approved by the ethics committee of the Beijing University of
      Chinese Medicine (approval number: 2018BZHYLL0109). A SPIRIT checklist is
      available for this protocol. The trial was registered in Chinese Clinical Trial
      Registry (WHO ICTRP member). Registration number: ChiCTR-BON-17010840.

PMID- 30235687
TI  - Ventricular repolarization wave variations during the amiodarone treatment
      course.
AB  - The aim of this study was to assess ventricular repolarization wave variations
      during the amiodarone treatment course for patients with ventricular arrhythmias
      and atrial fibrillation.Sixty-nine patients with ventricular arrhythmias and 9
      patients with persistent atrial fibrillation were treated with intravenous
      injection of a 150 mg loading dose of amiodarone, followed by 1 mg/minute for 6
      hours and 0.5 mg/minute for 48 hours. After the initial 24 hours of intravenous
      injection, amiodarone was also administered orally at a dose of 0.2 g tid for 1
      week; followed by 0.2 g bid for 1 week and 0.2 g qd for maintenance. During the
      procedure, the heart rate, QT, QTc, QTd, QTcd TpTe, TpTe-c, TpTe-d, TpTe/QT, and
      QTp were measured on days 1, 3, 7, 10, 14, 17, and 20 of amiodarone treatment.The
      control rate of arrhythmias was 91.0% (71/78). The heart rate dropped
      significantly on the 7th day after treatment initiation and reached the minimal
      value on day 14. The QT interval was prolonged from day 3; TpTe was prolonged
      from day 7 to day 14; QTp was prolonged from day 1 to day 20. The longest QT
      interval (441.2 +/- 33.9 ms) and TpTe (95.0 +/- 18.0 ms) occurred on day 14. QTc,
      QTd, QTcd, TpTe-c, TpTe-d, and TpTe/QT showed no significant changes throughout
      the treatment.Amiodarone lowers the heart rate, prolongs QT and QTp intervals,
      and transiently prolongs TpTe. However, it has no effects on QTc, QTd, QTcd, TpTe
      c, TpTe-d or TpTe/QT. Amiodarone prolongs QT interval evenly, showing no effects
      on repolarization dispersion. TpTe/QT is a better indicator of ventricular
      transmural repolarization dispersion compared with TpTe.

PMID- 30235688
TI  - Shen-Ling-Bai-Zhu-San for ulcerative colitis: Protocol for a systematic review
      and meta-analysis.
AB  - BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD)
      at the colonic mucosa and submucosa. Shen-Ling-Bai-Zhu-San (SLBZS) is one of the
      most common formulations of traditional Chinese medicine (TCM) for the treatment
      of UC. However, its effects and safety remain uncertain. This protocol is
      described for a systematic review to investigate the beneficial effects and
      safety of SLBZS for UC. METHODS: We will systematically search for eligible
      studies in PubMed, the Cochrane library, Embase, the Chinese Biomedical
      Literature Database (CBM), the China National Knowledge Infrastructure (CNKI),
      and Wanfang Data (WAN FANG) until August 2018. The primary outcomes are the
      induction of remission and the maintenance of remission. The summary results will
      be pooled using the random-effects model or fixed-effects model according to the
      heterogeneity of the included studies. RESULTS: The results will be submitted to
      a peer-reviewed journal for publication. CONCLUSION: The conclusion of our
      systematic review will provide evidence to judge whether SLBZS is an effective
      intervention for patient with UC. PROSPERO REGISTRATION NUMBER: PROSPERO CRD
      42018100477.

PMID- 30235689
TI  - Efficacy and adverse reactions of methotrexate in the treatment of ocular
      cicatricial pemphigoid: A case series study.
AB  - The application of methotrexate (MTX) in the treatment of autoimmune diseases has
      been gradually increasing, but reports of MTX treatment for advanced ocular
      cicatricial pemphigoid (OCP) are extremely rare. This study investigated the
      efficacy and adverse reactions of low-dose MTX in patients with OCP.This was a
      retrospective, noncontrolled, case series study. Eleven patients diagnosed with
      advanced OCP (4 cases in stage III and 7 cases in stage IV) were enrolled.
      Treatment by oral administration of MTX (7.5 +/- 2.5 mg) alone was performed.
      Visual acuity of the patients, conjunctival inflammation, cicatrization, ocular
      surface keratinization, and toxic side effects of drugs were evaluated.All
      patients enrolled in this study were females aged 32 to 83 years. Patients were
      followed up for 4 to 33 months. Low-dose MTX improved visual acuity of 3 cases (6
      eyes, 27.3%). Conjunctival inflammation of 5 patients (10 eyes) rested after
      treatment, and conjunctival inflammation of 3 cases (6 eyes, 27.3%) was decreased
      with an effective rate of 72.7%. Cicatrices of 8 cases (15 eyes) showed
      degeneration after treatment with an effective rate of 71.4% (15/21). Ocular
      surface keratinization receded in 4 cases with an effective rate of 66.7%. None
      of the patients discontinued the treatment due to severe toxic side effects. All
      patients tolerated mild drug-induced gastrointestinal reactions. Three patients
      terminated the treatment in advance after 4 to 6 months due to no improvement in
      the disease condition.Observation of clinical efficacy and safety findings
      demonstrated that low-dose MTX can be used to treat patients with advanced OCP.

PMID- 30235690
TI  - Effect of successful revascularization on left ventricular diastolic dysfunction
      in patients with aortoiliac occlusive disease.
AB  - Aortoiliac occlusive disease (AIOD) affects the systemic vascular resistance and
      increases the afterload because the left ventricle (LV) must work harder to eject
      blood into a smaller vascular bed. This study was to determine whether successful
      revascularization of AIOD is associated with improvement of left ventricular
      diastolic dysfunction (LVDD).A total of 37 patients with AIOD (34 men and 3
      women; age 65.1 +/- 7.2 years) were analyzed. The primary endpoint was defined as
      the change in the mitral E/E' ratio.There were no significant changes in the E
      velocity (from 0.7 +/- 0.2 to 0.7 +/- 0.2 m/s, P-value = .153), A velocity (from
      0.8 +/- 0.2 to 0.9 +/- 0.2 m/s, P-value = .169), LAVI (from 36.1 +/- 18.7 to 33.9
      +/- 15.7 mL/m, P-value = .176), E/A ratio (from 0.9 +/- 0.4 to 0.8 +/- 0.2, P
      value = .091), and E' velocity (from 6.5 +/- 2.0 to 6.9 +/- 2.1 m/s, P-value =
      .068). However, successful revascularization significantly reduced the E/E' ratio
      (from 14.1 +/- 5.7 to 11.7 +/- 3.3, P-value = .015). Additionally, a significant
      increase in the A' velocity (from 9.1 +/- 1.9 to 10.0 +/- 2.2 m/s, P-value =
      .029) and a decrease in the LA diameter (from 40.7 +/- 6.4 to 38.6 +/- 6.6 mm, P
      value = .014) were noted.Our results show that a successful revascularization of
      AIOD was associated with an improved E/E' ratio.

PMID- 30235691
TI  - Outcomes of trans-anal natural orifice specimen extraction combined with
      laparoscopic anterior resection for sigmoid and rectal carcinoma: An
      observational study.
AB  - Colorectal carcinoma is currently the third most frequent cancer worldwide.
      Conventional open surgery was replaced by laparoscopic anterior resection with
      total mesorectal excision for the treatment of sigmoid and rectal carcinomas;
      however, it needed an incision to harvest the specimen, which contributed to
      complications. In 2013, trans-anal natural orifice specimen extraction
      laparoscopic anterior resection (Ta-NOSE-LAR) to treat sigmoid and rectal
      carcinoma was performed in our hospital for the first time. The aim of this study
      was to investigate the outcomes of Ta-NOSE-LAR in sigmoid and rectal
      carcinoma.Seventy-three patients diagnosed with sigmoid and rectal carcinoma were
      enrolled between September 2013 and June 2016. Thirty-five patients underwent Ta
      NOSE-LAR, whereas the others underwent traditional laparoscopic anterior
      resection (LAR). We compared the operative data, postoperative complications,
      pathological evaluation results, and incision-related complications between the 2
      groups.Our result showed that the operative time, specimen length, tumor size,
      amount of total lymph nodes, and lymph node metastasis between the 2 groups were
      not statistically different. Further, without abdominal scaring for harvesting
      the specimen, the operative blood loss (49.29 +/- 14.63 vs 69.29 +/- 13.54 mL, P
      < .001) and post-operation hospital stay (5.77 +/- 0.94 vs 6.76 +/- 0.75 days, P
      < .001) of the Ta-NOSE-LAR group were less than those of the LAR group. Besides,
      the follow-up data showed that 2 patients were lost to follow-up, and 1 patient
      had liver metastasis 2 years after surgery in the LAR group, whereas the others
      showed no regional recurrence, distant metastases, or critical complications.Ta
      NOSE-LAR is a valuable and alternative surgical method to treat sigmoid and
      rectal carcinoma, with the advantages of being a scarless procedure and having a
      lower post-operation hospital stay duration.

PMID- 30235692
TI  - Motor vehicle accident mortality by elderly drivers in the super-aging era: A
      nationwide hospital-based registry in Japan.
AB  - Motor vehicle accidents (MVAs) are one of the major public health burdens
      worldwide. In particular, MVAs by elderly drivers have been significantly
      increasing in recent years in industrialized countries. This study aimed to
      assess the MVA characteristics and outcomes caused by elderly drivers in
      Japan.Japan Trauma Data Bank (JTDB) is a prospective, nationwide, hospital-based
      registry for trauma patients from 256 institutions in Japan. This study enrolled
      all MVA drivers older than the legal age for driving between 2004 and 2015. The
      included patients were divided into the following 3 groups: adults (aged <=64
      years), young-old (aged 65-74 years), and old-old (aged >=75 years). The primary
      outcome was in-hospital mortality. The trend in the proportion of MVAs caused by
      the young-old or the old-old group was evaluated using the Cochran-Armitage trend
      test. To assess the association of the old-old group with in-hospital mortality,
      compared with the adult group, we used multivariable logistic regression
      analysis.During the study period, a total of 236,698 trauma patients were
      registered, and 39,691 patients (16.8%) were eligible for our analysis. The
      proportion of MVAs caused by elderly drivers aged >=65 years significantly
      increased from 11.7% in 2004 to 23.8% in 2015 (P < .001). As for the primary
      outcome, unadjusted in-hospital mortality increased with age, but decreased year
      by-year irrespective of the age group. In multivariable logistic regression
      analysis, in-hospital mortality was significantly higher in the old-old group
      than in the adult group [17.3% (584/3372) vs 8.0% (2556/31,985); adjusted odds
      ratio 4.80; 95% confidence interval 4.06-5.67].In the super-aging society of
      Japan, the proportion of MVAs by elderly drivers increased year-by-year, and the
      mortality rate was highest in those aged above 75 years.

PMID- 30235693
TI  - No association between C-reactive protein and depressive symptoms among the
      middle-aged and elderly in China: Evidence from the China Health and Retirement
      Longitudinal Study.
AB  - The depressive symptoms have been associated with increased disabilities, and the
      depressive symptoms-related elevation of high C-reactive protein (CRP) has been
      proposed as a possible mechanism. We examined the relations between CRP and
      depressive symptoms among the middle-aged and elderly in China.A longitudinal
      sample of the middle-aged and elderly (4404 men and 5055 women) who were
      interviewed in the 2011 China Health and Retirement Longitudinal Study was used.
      A multivariate logistic regression analysis was used to examine the effects of
      sociodemographic characteristics, lifestyle, activity status, physical exercise,
      systolic blood pressure, low-density lipoprotein (LDL), high-density lipoprotein
      (HDL), triglycerides, body mass index (BMI), and CRP levels on depressive
      symptoms.The mean age in the study was 60.26 years [standard deviation (SD) +/-
      9.25; 46.56% men]. The mean CPR level was 2.79 mg/L (range, 0.01-178.10; SD +/-
      7.80). Depression scores ranged from 0 to 30 with a mean 8.65 (SD +/- 6.33). The
      prevalence of depressive symptoms was 38.49% in the total population, 31.04% in
      men and 44.99% in men. Compared with baseline CRP levels (<=1.00 mg/L), the
      depressive symptoms are only weakly correlated with CRP levels among women [CRP
      1.01-3.00 mg/L: odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.73-0.98;
      CRP 3.01-10.00 mg/L: OR = 1.25, 95% CI = 1.03-1.51; CRP >10 mg/L: OR = 1.41, 95%
      CI = 1.06-1.88]. After adjusting for age, education, marital status, hukou,
      residence, cigarette smoking, alcohol drinking, eating meals, activity status,
      major accidental injury, diseases, health status, physical exercise, systolic
      blood pressure, LDL, HDL, triglycerides, and BMI, depressive symptoms were not
      associated with subsequent high CPR levels among the middle-aged and elderly (CRP
      1.01-3.00 mg/L: OR = 0.93, 95% CI = 0.83-1.03; CRP 3.01-10.00 mg/L: OR = 0.95,
      95% CI = 0.82-1.10; CRP >10 mg/l: OR = 1.11, 95% CI = 0.88-1.39).Our data do not
      support an association between CRP and depressive symptoms in both middle-aged
      and elderly men and women among china.

PMID- 30235694
TI  - Patterns of care for glaucoma patients in Korea from 2002 to 2013 using the
      national health insurance service claims data.
AB  - Due to the rapidly increasing life-expectancy, the prevalence of glaucoma has
      increased steadily in recent years. We aimed to evaluate the patterns of care and
      primary treatment strategy patterns in Korea according to glaucoma subtypes to
      assess the quality of care for glaucoma patients.In this serial cross-sectional
      survey, the claims data from the Korean National Health Insurance Service was
      used to identify and group glaucoma patients into primary open-angle glaucoma
      (POAG), primary angle-closure glaucoma (PACG), other types of glaucoma, and
      ocular hypertension from 2002 to 2013. Records for outpatient visits,
      hospitalizations, drug prescriptions, admissions, and surgical interventions were
      used to determine the patterns of care and identify primary treatment
      strategies.Both the prevalence (0.11% in 2002 to 0.43% in 2013) and incidence
      rates (0.06% in 2003 to 0.11% in 2013) for glaucoma increased over time. The mean
      number of outpatient visits increased (4.9-6.0 visits per year), while the
      proportion of hospitalized patients (2.3-1.0% of patients) and duration of
      hospital stay (4.5-3.4 days among hospitalized patients) decreased between 2002
      and 2013 for patients with POAG. The proportion of patients not being managed by
      medication or surgery decreased, with POAG and PACG patients receiving
      medications increasing from 70.9% and 59.2% in 2002 to 88.4% and 63.3% in 2013,
      respectively. Finally, while the proportion of trabeculectomy decreased (22.2% to
      10.0% of surgical procedures in 2002 and 2013, respectively), more patients with
      PACG have received iridectomy (59.3% to 86.0% of surgical procedures in 2002 and
      2013, respectively).Between 2002 and 2013, the pattern of care for both patients
      with POAG and PACG has shifted toward management by outpatient visits and
      intervention with anti-glaucoma medications in Korea.

PMID- 30235695
TI  - Job preferences for medical students in China: A discrete choice experiment.
AB  - Although the number of medical workers has increased rapidly, its scarcity in
      rural areas remains a serious problem in China. This study aimed to investigate
      medical students' stated preferences when choosing a job, so as to assist policy
      makers with designing alternative interventions to address the unbalanced
      distribution of the health workforce in China.A discrete choice experiment (DCE)
      was conducted to elicit the job preferences of final year medical students.
      Attributes include work location, hospital type, monthly income, bianzhi (which
      can be loosely regarded as state administrative staffing), work environment,
      Training and career development opportunity. This study was carried out during
      April to June 2017 in 4 medical universities in Shandong Province, China. Mixed
      logit models were used to analyze the relative importance of job attributes.A
      total of 519 medical students participated in the survey. All 6 attributes were
      statistically significant with the expected sign and demonstrated the existence
      of preference heterogeneity. In the main effects mixed logit model, working in
      the city and a superior working environment were most strongly associated with
      job preference. A relatively unexpected finding was the relatively lower utility
      of offering bianzhi in job preferences. Subgroup analysis showed that females and
      those who have an urban background were significantly willing to pay more for
      working in the city. The most preferred scenario for medical students was to
      select a better work environment job in a tertiary hospital in the city, which
      could offer 9000 CNY monthly, with sufficient training and career development
      opportunities and bianzhi.Both monetary and nonmonetary intervention could be
      considered by policy makers to attract medical students to work in rural areas in
      China. There exists preference heterogeneity on medical students' job
      preferences, which should also be taken into account in developing more effective
      policy incentive packages.

PMID- 30235696
TI  - A spontaneous bilateral tubal pregnancy: A case report.
AB  - RATIONALE: Ectopic pregnancy (EP) is a condition in which a fertilized oocyte
      implants outside the uterine. Spontaneous bilateral tubal pregnancies are the
      rarest form of ectopic and are considered spontaneous when no fertility
      treatments are involved. There are few prior cases. Here I report a case of
      spontaneous bilateral tubal pregnancy. PATIENT CONCERNS: A 24-year-old female
      with long lasting vaginal bleeding of 29 days duration. DIAGNOSES: Transvaginal
      ultrasound observed small complex masses on both adnexal sides without
      intrauterine gestational sac, and the hCG level was 21438 IU/L. But diagnosing
      based only on imaging findings and blood test result was difficult.
      INTERVENTIONS: Operative laparoscopy with salpingectomy bilaterally. OUTCOMES:
      Villi were clearly shown in both resected tubes. A spontaneous bilateral tubal
      pregnancy was confirmed finally and the patient recovered uneventfully. LESSONS:
      Women of reproductive age with irregular menstruation should get access to
      diagnosis and appropriate treatment without delay. Salpingotomy should also be
      considered if the patient had a strong wish for future pregnancy. Developments of
      diagnosis and management of such condition are strongly called for.

PMID- 30235697
TI  - Traditional Chinese medicine decreases the obstructive uropathy risk in
      uterovaginal prolapse: A nationwide population-based study.
AB  - Traditional Chinese medicine (TCM) is a popular treatment for voiding dysfunction
      in Eastern countries. However, no previous studies have investigated the effects
      of TCM on preventing obstructive uropathy in uterovaginal prolapse women. We
      conducted a large-scale nationwide population-based cohort study to investigate
      the relationship between TCM and obstructive uropathy in uterovaginal prolapse
      women. This is a retrospective cohort study with the Taiwan National Health
      Insurance Research Database (NHIRD). The study population was newly diagnosed
      uterovaginal prolapse patients between 1997 and 2010 year. Among patients, 762
      uterovaginal prolapse patients in this cohort. Significant adjusted HRs of urine
      retention or hydronephrosis in Cox proportional hazard models were uterovaginal
      prolapse (hazard ratio [HR]: 1.74, 95% confidence intervals [CI]: 1.43-2.14), age
      40 to 64 years (1.51, 1.01-2.27), >=60 years (3.52, 2.32-5.34), DM (1.52, 1.23
      1.89), hypertension (1.38, 1.13-1.7), constipation (1.35, 1.05-1.75), urinary
      tract calculi (1.54, 1.06-2.23), and TCM users (0.34, 0.28-0.41). The Kaplan
      Meier analysis showed a higher incidence rate of urine retention or
      hydronephrosis in the uterovaginal prolapse cohort compared with that of the
      without uterovaginal prolapse cohort. The results of this nationwide population
      based study support a relationship between TCM and a reduced risk of obstructive
      uropathy in uterovaginal prolapse women.

PMID- 30235698
TI  - A new pathogenic mutation of the BRCA1 gene in a patient with ovarian cancer: A
      case report.
AB  - RATIONALE: The breast cancer susceptibility gene (BRCA) is an important tumor
      suppressor gene and tumor susceptibility gene. Germ line BRCA1/2 mutations
      significantly increase the risk of breast cancer and other cancers in women.
      PATIENT CONCERNS: A 48-year-old woman was diagnosed with breast cancer at the age
      of 42 and subsequently diagnosed with ovarian cancer at the age of 48. Her sister
      had a history of breast cancer and her mother died from ovarian cancer.
      DIAGNOSES: The patient has a family history of tumors. BRCA1/2 mutations was
      proved in this family members. INTERVENTIONS: Sanger sequencing was used to
      evaluate the BRCA1/2 gene status of the patient and her sister to identify the
      genetic mutation sites. OUTCOMES: They had the same genetic mutation, namely, the
      c.3487_3488insA (p.Thr1163AsnfsX2) mutation in the BRCA1 gene, which is a novel
      mutation. LESSONS: This novel mutation may be a new pathogenic mutation of the
      BRCA1 gene. Its relationship to breast and ovarian cancers needs to be further
      verified in more patient cases. Moreover, mutant protein functions in both cell
      and animal models are also needed.

PMID- 30235699
TI  - Psychometric properties of the short-form UCLA Loneliness Scale (ULS-8) among
      Chinese adolescents.
AB  - Loneliness is prevalent and severe among adolescents, indicating the need for a
      reliable, valid, and concise instrument for detecting adolescent loneliness. This
      study aims to examine the psychometric properties of the Chinese version of the
      short-form UCLA Loneliness Scale (ULS-8) among Chinese adolescents.Computer
      assisted self-interviewing was used to complete the questionnaire among 3480
      junior or senior high school students aged 10 to 19 years. Construct validity was
      assessed using exploratory factor analysis (EFA) and confirmatory factor analysis
      (CFA). To test the concurrent validity and convergent validity of the scale, a
      single loneliness item and variables such as depression, suicidal ideation, and
      quality of interpersonal relationships were used. For reliability, Cronbach alpha
      and test-retest correlation were computed.Construct validity and internal
      consistency showed that the ULS-6, which excluded 2 reverse-scored items from the
      ULS-8, had stronger psychometric properties than the ULS-8. The convergent
      validity and concurrent validity were also supported by the study results. The
      overall Cronbach alpha of the ULS-6 was 0.878 and the test-retest reliability
      coefficient was 0.663.The ULS-6 showed satisfactory reliability and validity in
      this study, suggesting that this instrument can be used in the measurement of
      loneliness among Chinese adolescents.

PMID- 30235700
TI  - Isolated Langerhans cell histiocytosis of the spleen: A case report.
AB  - RATIONALE: Langerhans cell histiocytosis (LCH) is a relatively rare disorder
      characterized by the proliferation of abnormal Langerhans cells. Splenic
      involvement usually presents in children with multisystem LCH, and isolated LCH
      of the spleen is a very rare disease. Herein, we report a case of isolated
      splenic LCH in an adult man. PATIENT CONCERNS: We report a case of isolated
      splenic LCH that first manifested with recurrent left upper abdominal pain.
      DIAGNOSIS: Unenhanced CT revealed multiple nodular lesions located at the spleen.
      Magnetic resonance imaging speculated that these lesions were lymphomas. On the
      basis of histopathological and immunohistochemical findings, the diagnosis of
      isolated splenic LCH was confirmed. INTERVENTION AND OUTCOMES: The patient
      underwent splenectomy. Histopathologic examination revealed the proliferation of
      Langerhans cell. Immunohistochemical staining revealed that cells of the tumor
      were positive for S-100, CD1a, CD45RO, and Vimentin. The patient is alive without
      recurrence 9 years after operation. LESSONS: Isolated LCH of the spleen may have
      a favorable prognosis and splenectomy is an effective therapeutic method.

PMID- 30235701
TI  - EBV VCA IgM and cytomegalovirus IgM dual positivity is a false positive finding
      related to age and hepatic involvement of primary Epstein-Barr virus infection in
      children.
AB  - Primary Epstein-Barr virus (EBV) infection is common in childhood, and dual
      positivity of serum EBV IgM and cytomegalovirus (CMV) IgM antibodies occur in
      some cases. This study aimed to evaluate the cause of EBV and CMV IgM dual
      positivity to determine whether it represents a false-positive finding or a true
      coinfection.A total of 494 children diagnosed with primary EBV infection,
      manifesting as infectious mononucleosis, were recruited. The diagnosis was based
      on positive EBV viral capsid antigen (VCA) IgM antibodies, and serum CMV IgM
      antibodies and liver enzymes were also evaluated in 149 subjects.Of 149 children
      with primary EBV infection, 40 (26.8%) had serum EBV VCA IgM and CMV IgM dual
      positivity. However, true CMV infection was confirmed only in 1 child of 40
      (2.5%) who was positive for both serum CMV Ag and urine CMV polymerase chain
      reaction (PCR) and negative for serum CMV IgG antibody. Among the children with
      primary EBV infection, the rate of dual positivity was higher in infants and
      lower in adolescents (P = .013). Liver enzymes were more significantly elevated
      in children with dual positivity than in those with negative results for CMV IgM
      antibodies (P = .026), which correlated with the serum EBV and CMV IgM
      titers.Serum EBV and CMV IgM dual positivity are more prevalent in children with
      primary EBV infection than what was previously reported. Our results indicate
      that serum EBV and CMV IgM dual positivity represents a false-positive finding,
      as opposed to an actual CMV coinfection, possibly due to antigenic cross
      reactivity.

PMID- 30235702
TI  - Implementation of temporal lobe contouring protocol in head and neck cancer
      radiotherapy planning: A quality improvement project.
AB  - Temporal lobe necrosis as result of radiation for nasopharyngeal cancer (NPC)
      occurs up to 28% of NPC patients. The only effective mitigation is by strict
      adherence to temporal lobe dose tolerances during radiotherapy planning, which in
      turn hinges on accurate temporal lobe delineation. We aim to improve the accuracy
      and to standardize temporal lobe contouring for patients receiving head and neck
      radiotherapy for NPC in a tertiary teaching hospital in Singapore.The baseline
      data were obtained from 10 patients in the diagnostic phase and the effect of
      interventions were measured in 37 patients who underwent head and neck
      radiotherapy over a 6-month period.We conducted the project based on the Clinical
      Practice Improvement Program methodology. The baseline pooled mean percentage
      variation in temporal lobe contouring was 39.9% (0.8%-60.2%). There was a low
      level of temporal lobe contouring concordance and this provided the impetus for
      implementation of strategies to improve the accuracy and reproducibility of
      temporal lobe contouring. The interventions included supervision and training of
      radiation therapists and residents in temporal lobe contouring, and
      standardization of temporal lobe contouring with a protocol and contouring
      atlas.Thirty-seven patients were treated during the study period from June to
      November 2014. Following implementation of the first set of interventions, the
      pooled mean percentage variation in temporal lobe contouring decreased but was
      not sustained. The implementation of the second set of interventions resulted in
      a decrease from 39.9% (January to September 2014) to 17.3% (October to November
      2014) where P = .004 using t test. Weekly variation was seen throughout the study
      period but the decrease was sustained after standardizing and providing a
      contouring atlas for temporal lobe contouring.Temporal lobe contouring can be
      standardized through effective implementation of a temporal lobe contouring
      protocol and atlas.

PMID- 30235703
TI  - Herbal medicine Sihogayonggolmoryeo-tang or Chai-Hu-Jia-Long-Gu-Mu-Li-Tang for
      the treatment of post-stroke depression: A protocol for a systematic review and
      meta-analysis.
AB  - INTRODUCTION: This systematic review protocol describes the methods that will be
      used to evaluate the efficacy and safety of herbal medicine Sihogayonggolmoryeo
      tang (SGYMT) or Chai-Hu-Jia-Long-Gu-Mu-Li-Tang for the treatment of post-stroke
      depression. METHODS AND ANALYSIS: The following electronic databases will be
      searched up to July 2018 without language or publication status restrictions:
      MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE,
      Allied and Complementary Medicine Database (AMED), Cumulative Index to Nursing,
      and Allied Health Literature (CINAHL), and PsycARTICLES. We will also search
      Korean and Chinese databases. Any clinical randomized controlled trials related
      to SGYMT treatment for post-stroke depression will be included. Changes in the
      degree of depression and adverse events will be assessed as primary outcomes. The
      total effective rate and changes in neurological function, activities of daily
      living, and quality of life will be evaluated as secondary outcomes. Study
      selection, data extraction, assessment of study quality, and evaluation of the
      quality of evidence for the main findings will be performed independently by 2
      researchers. The data synthesis and analysis will be performed using RevMan
      version 5.3. The results will be expressed as a risk ratio for dichotomous data
      and as the mean difference or standardized mean difference for continuous data.
      Data will be synthesized by either a fixed-effects or random-effects model
      according to a heterogeneity test or the number of studies included in the meta
      analysis. The methodological quality of the included studies will be evaluated
      using the Cochrane Collaboration's risk of bias tool. The quality of evidence for
      each main outcome will be evaluated using the Grading of Recommendations
      Assessment, Development, and Evaluation (GRADE) approach. ETHICS AND
      DISSEMINATION: Ethical approval is not required because individual patient data
      are not included. The findings of this systematic review will be disseminated
      through a peer-reviewed publication or conference presentations. PROSPERO
      REGISTRATION NUMBER: CRD42018102939.

PMID- 30235704
TI  - Effectiveness and safety of fluoroscopy-guided acupuncture for subacromial
      impingement syndrome: A protocol for a randomized, patient-assessor blind,
      parallel clinical trial.
AB  - INTRODUCTION: Subacromial impingement syndrome (SIS) is one of the most common
      diseases inducing shoulder pain. Acupuncture is a source of pain relief that has
      been used for SIS; however, there is no clinical study about image-guided
      acupuncture for SIS. The aim of this study is to evaluate the effectiveness and
      safety of fluoroscopy-guided acupuncture in patients with SIS. METHODS: This is
      the protocol for a randomized, patient-assessor blind, parallel clinical trial
      comparing fluoroscopy-guided acupuncture to acupuncture without fluoroscopy.
      There will be a 1-week run-in period before random allocation to 2 groups. The
      total duration of the clinical trial will be 3 weeks including 2 weeks for the
      follow-up period. A total of 57 participants will be enrolled for the clinical
      trial. Acupuncture will be conducted in 2 sessions for each group, once at
      baseline and once at the 1-week mark. The primary outcome will be 100 mm pain
      visual analogue scale. Secondary outcomes will include the Neer and Hawkins test,
      the Modified Constant Murley Score scale, the Shoulder Pain And Disability Index,
      the patient satisfaction degree, and the accuracy rate of acupuncture. For the
      evaluation of safety, adverse events will be monitored. DISCUSSION: We designed
      the clinical trial using image-guided acupuncture. This will be the first trial
      to study the effectiveness of image-guided acupuncture for SIS compared with
      acupuncture using the proportional measurements. TRIAL REGISTRATION: Clinical
      Research Information Service Registration Number is KCT0002751. Registered on
      March 23, 2018.

PMID- 30235705
TI  - CT, MRI, and F-18 FDG PET for the detection of non-small-cell lung cancer
      (NSCLC): A protocol for a network meta-analysis of diagnostic test accuracy.
AB  - BACKGROUND: Non-small-cell lung cancer (NSCLC) is a rare cancer in lung
      carcinomas and has been widely known as a difficult curable disease among all the
      tumors. However, early detection of malignant potential in patients with NSCLC
      has still been a huge challenge all around the world. CT, MRI, and F-18 FDG PET
      are all considered as good tests for diagnosing malignant NSCLC efficiently, but
      no recommended suggestion presents that which test among the 3 is the prior one
      in diagnose. We perform this study through network meta-analysis method, and to
      rank these tests using a superiority index. METHODS AND ANALYSIS: PubMed,
      Embase.com, and the Cochrane Central Register of Controlled Trials (CENTRAL) will
      be searched from their inception to March 2018. We will include diagnostic tests
      which assessed the accuracy of CT, MRI, and F-18 FDG PET for diagnosing NSCLC.
      The risk of bias for each study will be independently assessed as low, moderate,
      or high using criteria adapted from Quality Assessment of Diagnostic Accuracy
      Studies 2 (QUADAS-2). Network meta-analysis will be performed using STATA 12.0
      and R 3.4.1 software. The competing diagnostic tests will be ranked by a
      superiority index. RESULTS: This study is ongoing, and will be submitted to a
      peer-reviewed journal for publication. CONCLUSION: This study will provide
      systematically suggestions to select different diagnostic measures for detecting
      the early NSCLC. ETHICS AND DISSEMINATION: Ethical approval and patient consent
      are not required since this study is a network meta-analysis based on published
      studies. The results of this network meta-analysis will be submitted to a peer
      reviewed journal for publication. PROSPERO REGISTRATION NUMBER:
      PROSPEROCRD42018094542.

PMID- 30235706
TI  - Gasserian ganglion injected with Adriamycin successfully relieves intractable
      trigeminal nerve postherpetic neuralgia for an elderly patient: A case report.
AB  - RATIONALE: Effective treatments for trigeminal nerve postherpetic neuralgia (PHN)
      are limited. Adriamycin (doxorubicin) has been applied to the treatment of
      neuropathic pain. This study reports a new treatment: Adriamycin injected to
      Gasserian ganglion for an elderly patient with the intractable trigeminal nerve
      PHN. PATIENT CONCERNS: A 75-year-old man complained of lancing, burning pain in
      the right mandibular branch of the trigeminal nerve (V3) for 3 months after rash
      eruption. DIAGNOSES: Trigeminal nerve PHN. INTERVENTIONS: Approximately 0.5 mL of
      0.25% Adriamycin and 20 mg methylprednisolone injected to Gasserian ganglion
      through the foramen ovale with computer tomography guidance. OUTCOMES: The visual
      analog scale was 10 of 100 throughout the 1-month follow-up, and oxcarbazepine
      had also been tapered. The patient remained free of pain at the 12-month follow
      up. LESSONS: The treatment of Adriamycin injection to Gasserian ganglion is
      effective and safe, and may be considered as an alternative treatment for
      trigeminal nerve PHN. However, more research is needed to verify the validity.

PMID- 30235707
TI  - Analysis of endocrine hormone metabolism level in a Chinese patient with
      mucopolysaccharidosis IVA: A case report.
AB  - RATIONALE: Mucopolysaccharidosis IVA (Morquio A) is a catabolic
      mucopolysaccharide disorder caused by galactose-6-sulfate sulfatase deficiency.
      It is an autosomal recessive inherited disease. Previous reports on clinical
      characteristics of Morquio A mainly focused on growth retardation, skeletal
      deformities, and organ damage in children and adolescents, while the effects of
      mucopolysaccharide metabolism disorders on endocrine hormone metabolism level
      have not been reported. Herein, we reported the endocrine hormone metabolism in a
      case diagnosed as Morquio A. PATIENT CONCERNS: The patient was a 17-year-old girl
      with growth retardation, hearing loss, and severe skeletal dysplasia(scoliosis
      and chicken breast), and was evaluated to have normal nervous system function and
      intelligence by physicians. DIAGNOSES: She was diagnosed as Morquio A based on
      gene analysis, mucopolysaccharide-related enzymes and her clinical features.
      INTERVENTIONS: The patient didn't accepted the enzyme replacement therapy.
      OUTCOMES: She had a homozygous mutation of the GALNS gene. The b-glucuronidase
      content in the blood was reduced. The serum sodium, serum adrenocorticotropic
      hormone, and cortisol rhythms (8 AM) were decreased. The levels of PRA(plasma
      renin activity) , PAII(plasma angiotensin II), and PALD(plasma aldosterone) were
      elevated. Bone mineral density suggests osteoporosis. There were no abnormalities
      in bone metabolism indicators, growth hormone, thyroid hormone, and sex hormones.
      In summary, the level of endocrine hormones in patients with
      mucopolysaccharidosis IV changes. LESSONS: This is the report on endocrine
      hormone level in a patient with mucopolysaccharidosis IV in China. Due to the
      disease may have relatively incomplete adrenal function, which provides a basis
      for future understanding and diagnosis of this disease.

PMID- 30235708
TI  - Increased L1CAM (CD171) levels are associated with glioblastoma and metastatic
      brain tumors.
AB  - L1 cell adhesion molecule (L1CAM) is a member of the immunoglobulin-like cell
      adhesion molecule family that was shown to be associated with a worse prognosis
      in several human cancers. L1 ectodomain shedding via vesicles or exosomes has
      been detected in extracellular fluids after cleavage from the cell surface by
      metalloproteases. We evaluated the presence of L1CAM in cyst fluid and tissue
      from glioblastomas or brain metastases.The amount of L1CAM in cyst fluid of 9
      glioblastomas and 11 brain metastases was assessed using enzyme-linked
      immunosorbent assay (ELISA). Corresponding tumor tissue slices were stained
      immunohistochemically for L1CAM. Cerebrospinal fluid of 20 non-tumor patients
      served as controls.Mean levels of L1CAM in tumor cyst fluid were significantly
      higher in glioblastoma (6118 +/- 4095 ng/mL) and metastasis patients (8001 +/-
      6535 ng/mL) than in CSF of control patients (714 +/- 22 ng/mL). The
      immunohistochemical expression of L1CAM in corresponding tissue was significantly
      higher in metastases than in glioblastomas.The present study demonstrates high
      levels of L1CAM in cyst fluid of glioblastoma and metastatic brain tumors.
      Soluble L1CAM may represent a motility promoting molecule in cancer progression,
      a co-factor for development of tumor cysts and a target for new treatment
      strategies.

PMID- 30235709
TI  - The correlation between femoroacetabular impingement and superior retinacular
      artery interruption.
AB  - The aim of this study was to investigate the relationship between
      femoroacetabular impingement (FAI) and superior retinacular artery interruption
      using plain radiographs and digital subtraction angiography (DSA).Sixty-one
      patients included in this study were divided into 2 groups based on the superior
      retinacular artery integrity as evaluated on DSA images. Group A included intact
      arteries: 33 patients (24 men, 9 women,); group B included interrupted arteries:
      28 patients (21 men, 7 women). The parameters of abnormal radiographic findings
      thought to be associated with FAI, including positive crossover or figure-of
      eight sign of acetabulum, lateral center edge angle (LCEA) >40 degrees , Tonnis
      angle <0 degrees , positive posterior wall sign, alpha angle >50 degrees , and
      coxa profunda, were evaluated in all patients through plain radiographs.The cross
      over sign (Group A: 0, Group B: 8, P = .0035), LCEA (Group A: 1, Group B: 7, P =
      .0190), Tonnis angle (Group A: 3, Group B: 13, P = .0026), and alpha angle (Group
      A: 7, Group B: 17, P = .0039) differed significantly between both groups.
      However, there were no statistically significant differences in posterior wall
      sign (Group A: 9, Group B: 12, P = .3143) or coxa profunda (Group A: 12, Group B:
      8, P = .7096).Patients with interrupted blood supply of the superior retinacular
      arteries displayed more parameters of abnormal radiographic findings associated
      with FAI thereby indicating potential correlation between FAI and the
      interruption of superior retinacular arteries.

PMID- 30235710
TI  - Comparison of 1.5- and 3.0-T magnetic resonance imaging for evaluating lesions of
      the knee: A systematic review and meta-analysis (PRISMA-compliant article).
AB  - BACKGROUND: With conflicting results in the literature, it remains unclear
      whether a higher field strength automatically increases the sensitivity and
      specificity of magnetic resonance imaging (MRI) for detecting pathological
      lesions in the knee. Therefore, we performed a systematic review and meta
      analysis of studies comparing the diagnostic accuracy of 1.5- and 3.0-T MRI for
      lesions within the knee. METHODS: Sixteen studies were included in the meta
      analysis of the diagnostic accuracy of MRI for lesions of the knee joint, and
      areas under the curve (AUC) derived from the summary receiver operating
      characteristic curve analysis were determined for comparison of the diagnostic
      accuracy with differing magnetic field strength as well as for lesions in
      different tissues of the knee. Separate meta-analyses were performed for the
      diagnosis of lesions within articular cartilage, ligaments, and meniscus.
      RESULTS: For lesions within the articular cartilage, the AUC for 1.5-T MRI
      differed significantly from that for 3.0-T MRI (Z = 3.4, P < .05). However, for
      lesions within the ligaments and meniscus, the AUC values for 1.5-T MRI did not
      differ significantly from those for 3.0-T MRI (Z = 0.32, P > .05, and Z = 0.33, P
      > .05, respectively). CONCLUSION: Our results indicate that both 1.5-T and 3.0-T
      MRI offer high diagnostic accuracy and clinical relevance for knee injuries
      involving the meniscus or a ligament. However, the present meta-analysis
      indicates that 3.0-T MRI does offer greater diagnostic accuracy than 1.5-T MRI
      for articular cartilage lesions.

PMID- 30235711
TI  - Patients with chronic hepatitis C receiving sofosbuvir and ribavirin-based
      treatment, with or without interferon in Zhejiang, China: An observational study.
AB  - Hepatitis C virus (HCV) is one of the most important virus as the cause of liver
      disease in China. The aim of the present study was to explore whether sofosbuvir
      and ribavirin-based treatment can cure patients with chronic hepatitis C in
      eastern China. We examined a cohort of HCV-monoinfected patients and 9 patients
      agreed to participate in our treatment and research. The patients were diagnosed
      with chronic hepatitis C with or without cirrhosis. Nine patients including 4
      female and 5 male met the requirements for selection and were willing to
      participate in this experiment. Sofosbuvir and ribavirin-based treatment with or
      without interferon was given to the patients. Viral loads, cytokines, and
      chemokines were recorded during treatment and after treatment. After 2 weeks of
      sofosbuvir and ribavirin-based treatment, the viral load of patients decreased to
      limits of detection. Eight patients were cured. Patients had rapid virological
      response (RVR) with undetectable viral load at week 4 and sustained virological
      response (SVR). The interferon-inducible protein-10 (IP-10) decreased after the
      treatment. However, the patient with cirrhosis failed, as the virus reappeared
      during SVR4. At the same time, the IP-10 dramatically increased as the relapse of
      the HCV virus. In summary, the IP-10 has the potential to be the biomarker for
      the prognostic of HCV.

PMID- 30235714
TI  - Concomitant T-cell prolymphocytic leukemia and visceral leishmaniasis: A case
      report.
AB  - RATIONALE: T-cell prolymphocytic leukaemia (T-PLL) is a rare aggressive lymphoid
      disease featured by a significant increased lymphocyte count and obvious
      hepatosplenomegaly with poor prognosis. The concomitant presentation of T-PLL and
      visceral leishmaniasis (VL) has not previously been reported. PATIENT CONCERNS:
      The patient initially suffered from anorexia, skin pigmentation, fever and
      hepatosplenomegaly. Bone marrow smear described leishmania and antibody test was
      positive. VL was diagnosed and he was given antimony gluconate therapy. His
      symptoms recurred. DIAGNOSIS: A combination of serological rk39 test, morphologic
      evaluation and immunophenotyping by flow cytometry finally supported the
      diagnosis of concomitant VL and T-PLL. OUTCOMES: Amphotericin B was used for the
      treatment of VL first and a referral for treating T-PLL after recovery from VL
      was suggested. Unfortunately, the patient requested to be discharged. Telephone
      follow-up indicated that he died a few days after leaving the hospital. LESSONS:
      Due to the rarity of the disease combination, the pathogenesis association of T
      PLL and VL is unclear. However, a duly diagnosis is crucial for treatment. In
      immunosuppressed patients due to malignancies and treatment, VL should be
      considered as an opportunistic infection. In VL infections, the clinical
      manifestations mimicking hematological malignancies may cover up the underlying
      disease. Under such conditions, a complete work-up based on laboratory test is
      necessary to achieve a correct diagnosis.

PMID- 30235712
TI  - The dose response of sufentanil as an adjuvant to ropivacaine in cesarean section
      for relief from somato-visceral pain under epidural anesthesia in parturients
      with scarred uterus.
AB  - Visceral pain is common during epidural anesthesia with mini dose local
      anesthetics in parturients during cesarean section. To reduce or avoid this
      complication caused by traction on the abdominal viscera, this study aimed to
      determine the 50% effective dose (ED50) and 95% effective dose (ED95) of epidural
      sufentanil as an adjuvant combination with local anesthetics for relief visceral
      pain in parturients with scarred uterus undergoing elective cesarean section.One
      hundred parturients with scarred uterus undergoing elective cesarean section
      under epidural anesthesia were enrolled in this randomized, double-blinded, dose
      ranging study. Parturients received 5, 10, 15, 20, and 25 MUg epidural sufentanil
      as an adjuvant with 10 mL of 0.65% ropivacaine. Successful epidural anesthesia
      was defined as a sixth thoracic vertebra (T6) sensory level achieved within 20
      minutes after epidural drugs administration and/or no visceral pain by traction
      on the abdominal viscera during the cesarean section. The ED50 and ED95 were
      calculated with a logistic regression model.ED50 and ED95 of epidural sufentanil
      for successful of the pain-free from visceral pain were 10.7 MUg [95% confidence
      interval (CI): 2.4-14.4 MUg) and 28.1 MUg (95% CI: 19.4-44.0 MUg), respectively.
      The onset time to sensory block, maximum Bromage scale and duration of motor
      block were significant different with dose of sufentanil >20 MUg (P < .05,
      compared with the other dose groups). With the dose of epidural sufentanil >20
      MUg could result in an increase of incidence of maternals' adverse effects.
      Compared with a different dose of sufentanil, epidural administed sufentanil
      between 15 MUg and 20 MUg can maximize parturients' satisfaction.Our study showed
      that sufentanil could be used in combination with ropivacaine for relief from
      somato-visceral pain in patients with scarred uterus during elective cesarean
      section during epidural anesthesia, and that maximized parturients' satisfaction
      could be achieved when the use of sufentanil with the dose between 15 MUg and 20
      MUg for epidural anesthesia.

PMID- 30235713
TI  - Effect of high-volume hemofiltration on mortality in critically ill patients: A
      PRISMA-compliant systematic review and meta-analysis.
AB  - BACKGROUND: High-volume hemofiltration (HVHF) is widely used for blood
      purification in critically ill patients with systemic inflammatory syndromes. The
      purpose of this study was to evaluate the effect of HVHF on mortality at
      different follow-up periods in critically ill patients. METHODS: We
      systematically searched PubMed, Embase, and the Cochrane Library through April
      2017 to identify trials that evaluated the effect of HVHF on mortality in
      critically ill patients. Summary relative risks (RRs) and 95% confidence
      intervals (CIs) were employed to calculate the treatment effect using a random
      effects model. Eleven trials involving 1048 critically ill patients were included
      in this study. RESULTS: The summary results indicated no significant differences
      between HVHF and usual care for the incidence of 28-day mortality (RR: 0.93;
      95%CI: 0.80-1.08; P = .321), 7-day mortality (RR: 0.72; 95%CI: 0.50-1.03; P =
      .072), 60-day mortality (RR: 1.00; 95%CI: 0.86-1.16; P = .997), and 90-day
      mortality (RR: 1.01; 95%CI: 0.88-1.16; P = .927). Subgroup analysis suggested
      HVHF significantly reduced the risk of 28-day mortality (RR: 0.64; 95%CI: 0.42
      0.97; P = .035) if pooled the study sample size < 100. CONCLUSION: Our findings
      suggest HVHF significantly reduced the incidence of 28-day mortality when pooled
      the study sample size < 100. Further, HVHF had a marginal effect on the incidence
      of 7-day mortality.

PMID- 30235715
TI  - Preiser disease after repeated local glucocorticoid injections: A case report.
AB  - RATIONALE: Preiser disease or avascular necrosis (AVN) of the scaphoid causes
      intolerable wrist pain and malalignment of the carpal bones. In previously
      reported cases, patients have had a history of steroid use for systemic illness
      such as autoimmune hemolytic anemia, systemic lupus erythematosus, or renal
      transplantation, or have had other risk factors, such as smoking, alcoholism, or
      infection. In particular, systemic glucocorticoid therapy has been most commonly
      associated with the disease. Although there are reports of AVN of the scaphoid
      induced by systemic glucocorticoids, no prior report has associated AVN of the
      carpal bones with repeated local injections of glucocorticoids. PATIENT CONCERNS:
      We present a case in which it was strongly suspected that AVN of the scaphoid was
      induced by repeated local glucocorticoid injections. The patient had no history
      of excessive alcohol use, smoking, or trauma, except for local repeated steroid
      injections. DIAGNOSES: Initially, she had diagnosed with de Quervain's disease
      and was treated by repeated local glucocorticoid injections followed by surgery
      for de Quervain's disease. Five years after surgery for de Quervain's disease,
      the patient presented at our hospital with sudden onset of intolerable pain in
      her right wrist without a history of trauma. In spite of nonsurgical treatment
      with rest, immobilization, analgesia, and surgery, her wrist pain was not
      improved. After further repeated local steroid injections in her wrist,
      radiographs, and magnetic resonance imaging of her wrist showed the AVN of the
      scaphoid. INTERVENTIONS: Surgery was performed and the fragmented proximal
      scaphoid and the entire lunate were resected. OUTCOMES: The diagnosis was
      confirmed according to the histopathological examination of the proximal scaphoid
      bone, which showed the characteristic of AVN of the scaphoid. At follow-up
      evaluation, radiographs of the right wrist showed no progression of
      osteoarthritis. The patient had no tenderness or residual pain at the wrist and
      had no desire to pursue additional surgery. LESSONS: We have presented a case
      with AVN of the scaphoid, which was strongly suspected to be associated with the
      repeated local steroid injections. Further studies are required to more fully
      elucidate the association between AVN of the scaphoid and repeated local steroid
      injections.

PMID- 30235717
TI  - Investigating effective treatment factors in brief cognitive behavioral therapy
      for panic disorder.
AB  - Numerous studies have provided evidence for the effectiveness of cognitive
      behavioral therapy (CBT) on panic disorders (PDs). There has also been growing
      attention on brief CBT with regard to delivering intensive treatment efficiently.
      This study investigated the essential parts of mindfulness-based brief CBT to
      optimize treatment benefits.A total of 37 patients were retrospectively enrolled
      in this study. They were recruited from the anxiety/panic/fear clinic of Seoul
      National University Hospital. The patients participated in group CBT once a week
      for a total of 4 sessions over a 4-week period, when they were assessed using the
      Panic Disorder Severity Scale (PDSS), Anxiety Sensitivity Index-Revised (ASI-R),
      Albany Panic and Phobia Questionnaire (APPQ), State-Trait Anxiety Inventory
      (STAI), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Yale
      Brown Obsessive Compulsive Scale (Y-BOCS) before and after brief CBT. Twenty-nine
      patients completed the 1-month follow-up.There were significant reductions in
      PDSS (P < .001), ASI-R-fear of respiratory symptoms (P = .006), ASI-R-fear of
      publicly observable anxiety reaction (P = .002), ASI-R-fear of cardiovascular
      symptoms (P < .001), ASI-R-fear of cognitive dyscontrol (P = .001), ASI-R-Total
      (P < .001), APPQ-Agoraphobia (P = .003), APPQ-Total (P = .028), STAI-State
      anxiety (P < .001), STAI-Trait anxiety (P = .002), BAI (P = .003), and BDI (P <
      .001) scores. We also found significant associations between ASI-R-fear of
      cardiovascular symptoms, ASI-R-Total, and changes in PDSS scores. A stepwise
      multiple linear regression analysis indicated that anxiety sensitivity for fear
      of cardiovascular symptoms predicted an improvement in panic severity (beta =
      0.513, P = .004).Our findings suggested that behavioral aspects, especially
      physiological symptom control, needed to be considered in brief, intensive CBT
      for PD. The results also suggested that a mindfulness-based brief CBT approach
      might be particularly helpful for patients with PD who have severe cardiovascular
      symptoms.

PMID- 30235716
TI  - Comparative study of esketamine and racemic ketamine in treatment-resistant
      depression: Protocol for a non-inferiority clinical trial.
AB  - INTRODUCTION: The use of ketamine as an option in the treatment of depressive
      disorder is growing rapidly, supported by numerous clinical trials attesting its
      efficacy and safety. Esketamine, the S (+) enantiomer of ketamine, is the most
      widely used form in the anesthetic environment in some countries, and new studies
      have shown that it may also be effective in depression and with better
      tolerability. However, no study so far has directly compared esketamine with
      racemic ketamine. Here we propose a protocol of a clinical trial to evaluate
      esketamine as a noninferior medication when compared to ketamine in the treatment
      of patients with treatment-resistant depression. METHODS/DESIGN: This study
      protocol is for a randomized, controlled, double-blind noninferiority clinical
      trial. Subjects will be 18 years or older, with major depression characterized as
      treatment-resistant. Participants will receive a single infusion of either
      esketamine (0.25 mg/kg) or ketamine (0.5 mg/kg) over 40 minutes. The primary
      outcome will be the difference in remission rates between the 2 treatment arms at
      24 and 72 hours after drug infusion. Secondary outcomes will include other
      timepoints, measurements of cognition, dissociation, and blood biomarkers.
      DISCUSSION: A head-to-head study is the best way to evaluate whether the
      esketamine is in fact comparable to the racemic ketamine in terms of both
      efficacy and safety, and, if positive, it would be an initial step to increase
      the access to that type of treatment worldwide. ETHICS AND DISSEMINATION: The
      study was approved by the local Institutional Review Board (University Hospital
      Professor Edgard Santos-Federal University of Bahia-Number:
      46657415.0.0000.0049). Subjects will only participate after voluntarily agreeing
      and signing the Informed Consent Form. The study findings will be published in
      peer-reviewed journals and presented at national and international conferences.
      TRIAL REGISTRATION: This trial has been registered in the Japan Primary
      Registries Network (JPRN): UMIN000032355, which is affiliated with the World
      Health Organization.

PMID- 30235718
TI  - A case report of neuroendocrine tumor (G3) at lower rectum with liver metastasis.
AB  - RATIONALE: Rectal neuroendocrine tumor is a rare disease that is difficult to
      diagnose by clinical and imageological examinations. The treatment of rectal
      neuroendocrine tumors is still controversial. PATIENT CONCERNS: A 50-year-old
      woman complained of abdominal pain beneath the xiphoid process for 1 day.
      Physical checkup revealed tenderness at the right upper abdomen. A fecal occult
      blood test was positive. MRI showed an occupation lesion in the right lobe of the
      liver. Colonoscopy examination showed a lesion at the lower rectum with an
      ulcerated surface that was tough in texture. No abnormality was found in the
      tumor markers. DIAGNOSIS: Rectal neuroendocrine tumor (G3) with liver metastasis.
      INTERVENTIONS: Neoadjuvant chemotherapy followed by laparoscopic surgery was
      given. OUTCOMES: The patient followed up regularly in the outpatient department
      for 13 months after surgery, and no sign of recurrence was found. LESSONS:
      Neoadjuvant chemotherapy followed by laparoscopic surgery is a new idea for the
      treatment of rectal neuroendocrine carcinoma with distant metastasis, which
      offers favorable conditions for saving the anus during the surgery to enhance the
      patient's quality of life.

PMID- 30235720
TI  - The effect of metabolic health and obesity phenotypes on risk of hypertension: A
      nationwide population-based study using 5 representative definitions of metabolic
      health.
AB  - Although obesity is clearly identified as a risk factor for hypertension, the
      association between its different metabolic phenotypes and hypertension remains
      unclear. We aimed to investigate this association and compare the degree of
      association between metabolic health and obesity phenotypes defined by 5
      representative criteria and hypertension risk.This study used data from the China
      Health and Nutrition Survey 2009 wave, and the final analysis included 7632
      subjects aged 18 to 85 years with available fasting blood samples and
      anthropometric measurements. Body mass index was used to define nonobese and
      obese status in subjects (cut-off value, 25 kg/m), and metabolic health state was
      respectively defined by 5 published criteria: the Adult Treatment Panel (ATP)
      III, the Wildman, the Karelis, the homeostasis model assessment (HOMA), and the
      fasting blood glucose * triglyceride (TyG) criteria. Subjects were categorized
      into 4 phenotypes according to their metabolic health and obesity status:
      metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO),
      metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO).A
      total of 2171 subjects (28.4% of the study population) had hypertension, and
      hypertension prevalence was significantly increased as weight increased for both
      metabolically healthy and metabolically unhealthy subjects. Within the MHO
      phenotypes, the prevalence ranged from 22.7% to 38.6% according to the Wildman
      and HOMA criteria, respectively. Compared to the MHNO phenotype, the MHO
      phenotype had an increased risk of hypertension, and the adjusted odds ratios for
      hypertension in MHO subjects were 1.94 (95% confidence interval 1.60-2.35) using
      the ATP-III criteria, 1.98 (1.61-2.43) using the Wildman criteria, 2.37 (1.88
      2.99) using the Karelis criteria, 2.26 (1.96-2.61) using the HOMA criteria, and
      2.54 (2.14-3.00) using the TyG criteria, respectively. A similar significant
      pattern was found in the MUO and MUNO phenotypes for risk of hypertension.
      Furthermore, the MUO phenotype consistently revealed the strongest degree of
      association with hypertension, following by the MHO and the MUNO phenotype.Both
      metabolically unhealthy status and obese status contributed to a higher risk of
      hypertension in Chinese adults. The MHO phenotype was not a benign condition and
      had substantial risk of hypertension compared to the MHNO phenotype. Thus,
      metabolic health status and obesity should be monitored together when managing
      hypertension risk.

PMID- 30235721
TI  - Late complications of totally implantable venous access ports in patients with
      cancer: Risk factors and related nursing strategies.
AB  - The aim of this study was to assess the incidence rate and the risk factors for
      late complications associated with use of central totally implanted venous access
      devices (TIVAPs) in patients with cancer, and to devise nursing strategies to
      minimize late complications.This retrospective study included 500 patients with
      TIVAPs from 2012 to 2015. Multivariable logistic regression analysis was
      performed to assess the effect of sex, age, primary diagnosis, duration of
      surgery, and the length of hospital stay on the incidence of late complications
      of TIVAP.The cumulative maintenance period of TIVAP was 159,605 days. Late
      complications included catheter-related obstruction (n = 14; 2.8%), infection (n
      = 3; 0.6%), drug extravasation (n = 1; 0.2%), and catheter exposure (n = 1;
      0.2%). Multivariate analyses revealed that age, breast cancer, lung cancer, and
      gastric cancer were risk factors for the late complications associated with
      TIVAP.There was a low incidence of late complications with TIVAP use. Catheter
      related obstruction is the most frequent late complication of TIVAP. Risk factors
      for TIVAP-associated late complications include age and certain cancers, such as
      breast cancer, lung cancer, and gastric cancer.

PMID- 30235719
TI  - Hepatic toxicity following actinomycin D chemotherapy in treatment of familial
      gestational trophoblastic neoplasia: A case report.
AB  - RATIONALE: Familial hydatidiform mole is extremely rare while familial
      gestational trophoblastic neoplasia (GTN) has never been reported. Inspired by 2
      biological sisters with postmolar GTN and liver toxicity, we reviewed susceptible
      maternal-effect genes and explored the role of possible drug transporter genes in
      the development of GTN. PATIENT CONCERNS: We reported one Chinese family where
      the two sisters developed postmolar GTN while experiencing fast remission and
      significant hepatic toxicity from actinomycin D chemotherapy. DIAGNOSES: The
      index pregnancy was diagnosed with curettage. The following GTN was confirmed
      when there was a rise in beta-hCG for three consecutive weekly measurements over
      at least a period of 2 weeks. Computed tomography was used to identify lung
      metastasis. The elder sister was diagnosed with gestational trophoblastic
      neoplasia (III: 2) while the younger sister was diagnosed as III: 3 according to
      WHO scoring system. INTERVENTIONS: Patients were treated with actinomycin D of 10
      MUg/kg intravenously for 5 days every 2 weeks. When hepatic toxicity was
      indicated, polyene phosphatidyl choline and magnesium isoglycyrrhizinate were
      prescribed. OUTCOMES: Both patients responded extremely well to the 5-day
      actinomycin D regimen. Beta-hCG remained less than 2 mIU/ml after 5 cycles while
      computed tomography scan showed downsized pulmonary nodules. Both experienced
      significant rise in ALT and AST levels that could be ameliorated with
      corresponding medication. Monthly followed-up showed negative beta-hCG levels and
      normal liver enzyme levels. LESSONS: We speculated that the known or unknown
      NLRP7 and KHDC3L mutations might be correlated with drug disposition in liver
      while liver drug transporters such as P-glycoprotein family that are also
      expressed in trophoblasts might be correlated to GTN susceptibility. Future
      genomic profiles of large samples alike using next generation sequencing are
      needed to confirm our hypothesis and discover yet unknown genes.

PMID- 30235722
TI  - Associations between common ion channel single nucleotide polymorphisms and
      sudden cardiac death in adults: A MOOSE-compliant meta-analysis.
AB  - BACKGROUND: We sought to identify common ion channel single nucleotide
      polymorphisms (SNPs) associated with the occurrence of sudden cardiac death (SCD)
      to predict the incidence of SCD in clinical settings. METHODS: This study
      involved a systematic review and meta-analysis of ion channel SNPs and risk of
      SCD in adults. We searched public databases for studies published up to September
      19, 2017. We examined relationships between SNPs in common ion channel genes and
      the incidence of SCD. RESULTS: We collected data for 22 trials that included a
      total of 4149 patients who experienced SCD or had a high risk of SCD and assessed
      these data in our meta-analysis. An allelic model showed that rs11720524 in SCN5A
      clearly protected against SCD (odds ratio [OR]: 0.76; 95% confidence interval
      [95% CI]: 0.67-0.85; P < .001). Subgroup analysis showed that rs11720524 in SCN5A
      protected against SCD in Europeans and Caucasians but not in Koreans. The allelic
      model indicated that rs12296050 in KCNQ1 also had significant protective effects
      against SCD (OR: 0.85; 95% CI: 0.76-0.96; P = .007). Moreover, this model
      demonstrated that rs2283222 in KCNQ1 had a significant negative relationship with
      SCD (OR: 0.73; 95% CI: 0.62-0.85; P < .001). Rs12296050 in KCNQ1 protected
      against SCD in Koreans and Americans. Our results also showed that rs790896 in
      RYR2 was negatively associated with SCD in a dominant model (OR: 0.66; 95% CI:
      0.45-0.97; P = .033). CONCLUSIONS: Rs11720524 in SCN5A is negatively related to
      SCD in Europeans and Caucasians, and rs12296050 and rs2283222 in KCNQ1 and
      rs790896 in RYR2 clearly have protective effects against SCD.

PMID- 30235723
TI  - Unusual expansion of CD3+CD56+ natural killer T-like cells in peripheral blood
      after anticytokine treatment for graft-versus-host disease: A case report.
AB  - RATIONALE: Basiliximab and etanercept have achieved promising responses in
      steroid-refractory graft versus host disease (SR-GVHD). However, the in vivo
      immune changes following the treatment have not been elucidated. PATIENT
      CONCERNS: A 14-year-old boy presented with skin rash and diarrhea 20 days after
      haploidentical hemotopoietic stem cell transplantation. DIAGNOSES: We made the
      diagnose of grade 3 acute GVHD with skin and gastrointestinal involvement.
      INTERVENTIONS: After the failure of the first-line treatment with
      methylprednisolone, combined anti-cytokine therapies with basiliximab and
      etanercept were prescibed. OUTCOMES: He achieved complete remission by
      basiliximab and etanercept. Furthermore, we detected that donor CD3CD56 Natural
      killer T(NKT)-like cells expanded gradually after the period of lymphocytopenia
      caused by GVHD and anti-cytokine therapy. The expansion of NKT-like cells was in
      association with high serum IFN-gamma. NKT-like cells showed preferred
      proliferation in response to IFN-gamma and potent cytotoxicity against leukemia
      cells. The expansion persisted > 2 years and the patient had a leukemia-free
      survival of 66 months. LESSONS: Our case indicated that combined anti-cytokine
      treatment may reset the immune system and cause NKT-like cells to exhibit a
      predilection for expansion.

PMID- 30235724
TI  - Relation of metabolic syndrome and its components with risk of diabetic
      retinopathy: A meta-analysis of observational studies.
AB  - Emerging studies have reported the effects of metabolic syndrome (MetS) and its
      components on risk of diabetic retinopathy (DR), but the results remain
      controversial. Therefore, we performed a meta-analysis to evaluate the
      relationship between MetS and risk of DR.A meta-analysis of observational
      studies.Studies were searched from PubMed, Cochrane Library, and Elsevier
      databases from the start of the database up until November 30, 2017. Adjusted
      odds ratios (ORs) and its corresponding 95% confidence intervals (CIs) were
      extracted and pooled by using a random effects model.A total of 12 observational
      studies were included in this meta-analysis. When the MetS as a full syndrome,
      MetS was not associated with increased risks of type 1 (OR = 1.47, 95% CI 0.67
      3.24; P = .34) or type 2 (OR = 1.34, 95% CI 0.91-1.98; P = .14) DR. In addition,
      none of single component of MetS was associated with the risk of DR, including
      body mass index/waist circumference (BMI/WC) (OR = 0.92, 95% CI 0.75-1.13; P =
      .41), blood pressure (OR = 1.37, 95% CI 0.96-1.95; P = .08), high density
      lipoprotein (OR = 0.97, 95% CI 0.93-1.01; P = .19), and triglyceride (OR = 0.85,
      95% CI 0.63-1.15; P = .29). In the sensitivity analysis, the pooled OR values
      were not changed after we removed the included studies one by one.Based on recent
      published data, neither MetS nor its components are associated with an increased
      risk of DR.

PMID- 30235725
TI  - Adducted thumb as an isolated morphologic finding: an early sonographic sign of
      impaired neurodevelopment: A STROBE compliant study.
AB  - Fetal adducted thumbs have been described in association with hydrocephalus and
      other abnormalities, but in cases without other structural malformations the
      determination of prognosis and recurrence risk is challenging. The aim of our
      study is to analyze the characteristics, natural history, and postnatal outcome
      of such cases.A retrospective study was conducted over a period of 4 years in a
      tertiary referral center. All fetuses diagnosed as adducted thumbs without other
      structural malformations comprised the study group. Prenatal sonographic features
      and neonatal outcome are documented.There were 4 cases of fetal adducted thumbs
      diagnosed during the study period. No cases demonstrated other structural
      malformations throughout the gestation. A smaller head was noted in 2 cases
      during the follow-up, and all cases presented with polyhydramnios on the first or
      ensuing scans. Three cases died after birth due to swallowing or breathing
      difficulty, and the surviving 1 showed convulsion and mental retardation.Fetal
      adducted thumb might be an early and specific sonographic marker of impaired
      neurodevelopment. Close follow-up and genetic investigation should be performed
      in these cases. Ultrasound examination plays an important role in the prenatal
      diagnosis and counseling of cases without detailed prenatal genetic analysis.

PMID- 30235727
TI  - The efficacy and safety of Hanslim for obese patients: Study protocol for a
      multicenter, randomized, double-blind, multi-dose, placebo-controlled, phase IIb
      clinical trial.
AB  - BACKGROUND: This study aims to evaluate the efficacy, safety, and appropriate
      dose of Hanslim, a Korean traditional herbal medicine, for obese patients, when
      compared to a placebo. METHODS/DESIGN: This study is a randomized, double
      blinded, multicenter, multidose, placebo-controlled, phase IIb clinical trial. A
      total of 165 obese patients with a body mass index (BMI) of more than 30 kg/m or
      obese patients with a BMI of 27 to 29.9 kg/m and one or more risk factors such as
      hypertension, diabetes, or hyperlipidemia will be enrolled. Participants will be
      randomly assigned to 1 of 3 groups (high-dose, low-dose, or placebo) with a 1:1:1
      allocation ratio and will have 4 scheduled visits during the 12-week treatment
      period. The participants will be administered 2 tablets of Hanslim or placebo, 2
      times per day. The difference in the proportion of participants who lost weight
      by more than 5% from their baseline at 12 weeks compared to the placebo group
      will be examined as the primary efficacy outcome. Secondary efficacy outcomes
      include differences in body weight, BMI, body-fat percentage, fat mass, skeletal
      muscle mass, edema index, waist circumference, hip circumference, waist-hip
      ratio, serum lipid, blood glucose, C-reactive protein, and total score of Korean
      version of obesity-related quality of life after 12 weeks of treatment. Adverse
      events, laboratory test results, vital sings, and electrocardiography will be
      recorded to evaluate safety. DISCUSSION: This is the first prospective clinical
      trial to explore the efficacy and safety of Hanslim for obese patients. If the
      results provide the appropriate dosage of Hanslim, this study would contribute to
      the confirmatory evidence for the use of Hanslim as a treatment for obesity
      needed to conduct a large-scale, phase III clinical trial. The results will be
      published in a peer-reviewed journal. TRIAL REGISTRATION: Clinical Research
      Information Service, ID: KCT0002193. Registered on January 6, 2017.
      https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=7468.

PMID- 30235726
TI  - Effect of Yikou-Sizi powder hot compress on gastrointestinal functional recovery
      in patients after abdominal surgery: Study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Postoperative gastrointestinal dysfunction (PGD) is a common
      complication of patients who have undergone surgery. The clinical manifestations
      cause great discomfort to postoperative patients and can severely affect
      postoperative recovery. However, although various pharmacologic agents have been
      explored for several years, success has been limited. Because some commonly used
      drugs have caused adverse reactions and because abdominal surgery patients
      generally cannot consume food or medication during the perioperative period, we
      were prompted to try an external Chinese medicine treatment method. Yikou-Sizi
      powder hot compress is an efficient therapy in our hospital, but there is a lack
      of rigorous studies to certify the safety and effectiveness of its external use
      to improve gastrointestinal motility. This study aimed to introduce the clinical
      trial design and test the ability of Yikou-Sizi powder hot compress treatment to
      accelerate gastrointestinal functional recovery after abdominal surgery. METHODS:
      This study is a randomized controlled clinical trial. The participants will
      undergo laparoscopic colorectal cancer surgery and laparoscopic total
      hysterectomy. The primary outcome measure will be the gastrointestinal functional
      evaluation index, including the time to first passage of flatus, first
      defecation, first normal bowel sounds, and first consumption of
      liquid/semigeneral diet foods. According to good clinical practice (GCP), we will
      evaluate the clinical efficacy and safety of Yikou-Sizi powder hot compress and
      objectively study the acting mechanism of ghrelin. This pilot trial will be a
      standard, scientific, and clinical study designed to evaluate the effect of Yikou
      Sizi powder hot compress for the recovery of gastrointestinal function after
      surgery and determine its overall safety. DISCUSSION: This is the first study to
      describe the use of Yikou-Sizi powder hot compress to accelerate the recovery of
      gastrointestinal function after abdominal surgery. The study is designed as a
      randomized, controlled, clinical, large sample size and pilot trial. Evaluation
      will consist of combining the primary outcome measures with secondary outcome
      measures to ensure the objectivity and scientific validity of the study. Due to
      the observational design and the limited follow-up period, it is not possible to
      evaluate to what extent the connection between the observed improvement and the
      interventions represents a causal relationship. Efficient comparison between
      groups will be analyzed by chi-square test.

PMID- 30235728
TI  - Validation of the behavioral pain scale to assess pain intensity in adult,
      intubated postcardiac surgery patients: A cohort observational study - POL-BPS.
AB  - Patients after cardiac surgery experience significant pain, but cannot
      communicate effectively due to opioid analgesia and sedation. Identification of
      pain with validated behavioral observation tool in patients with limited
      abilities to self-report pain improves quality of care and prevents suffering.
      Aim of this study was to validate Polish version of behavioral pain scale (BPS)
      in intubated, mechanically ventilated patients sedated with dexmedetomidine and
      morphine after cardiac surgery.Prospective observational cohort study included
      postoperative cardiac surgery patients, both sedated with dexmedetomidine and
      unsedated, observed at rest, during a nociceptive procedure (position change) and
      10 minutes after intervention. Pain control was achieved using morphine infusion
      and nonopioid coanalgesia. Pain intensity evaluation included self-report by
      patient using numeric rating scale (NRS) and BPS assessments carried out by 2
      blinded observers.A total of 708 assessments were performed in 59 patients (mean
      age 68 years), predominantly men (44/59, 75%). Results showed very good
      interrater correlation between raters (interrater correlation scores >0.87). Self
      report NRS scores were obtained from all patients. Correlation between NRS and
      BPS was relatively strong during nociceptive procedures in all patients for rater
      A and rater B (Spearman R > 0.65, P < .001). Both mean NRS and BPS scores were
      significantly higher during nociceptive procedures as compared to assessments at
      rest, in both sedated and unsedated patients (P < .001).The results of this
      observational study show that the Polish translation of BPS can be regarded as a
      useful and validated tool for pain assessment in adult intubated patients. This
      instrument can be used in both unsedated and sedated cardiac surgery patients
      with limited communication abilities.

PMID- 30235729
TI  - Extended-spectrum beta-lactamase-producing E. coli septicemia among rectal
      carriers in the ICU.
AB  - The aim of this study was to identify risk factors for extended-spectrum beta
      lactamase (ESBL)-producing Escherichia coli (E coli) bloodstream infection (BSI)
      among carriers hospitalized between March 2011 and June 2016 at the ICU of the
      West China Hospital.The cases were patients with at least 1 episode of ESBL
      producing E coli BSI within 1 week after a positive rectal swab. Controls were
      selected randomly 1:2 among ESBL-producing E coli rectal carriers who did not
      develop BSI.Among 19,429 ICU patients, 9015 (46.4%) had a positive rectal swab
      for ESBL-producing E coli. Of them, 42 (0.5%) were diagnosed with ESBL-producing
      E coli BSI. The in-hospital mortality was higher for the BSI patients compared
      with controls (19.1% vs. 6.0%, P = .031). In the past 72 hours, patients in case
      group were more likely to use penicillin (odds ratio [OR] = 12.076; 95%
      confidence interval [CI]: 1.397-104.251, P = .02), cephalosporin (OR = 6.900; 95%
      CI: 1.493-31.852, P = .01), and carbapenem (OR = 5.422; 95% CI: 1.228-23.907, P =
      .03) as compared to patients in control group. Also, when compared to patients in
      control group, patients in case group were likely to stay for a longer time in
      ICU before positive rectal swab test (OR = 1.041, 95% CI: 1.009-1.075, P = .01)
      and have higher maximum body temperature before positive rectal swab (OR = 8.014;
      95% CI: 2.408-26.620, P = .001).Bacteremia owing to ESBL-producing E coli was
      associated with high antimicrobial exposure, hospital stay, and maximum body
      temperature.

PMID- 30235730
TI  - Predictive value of soluble ST-2 for changes of cardiac function and structure in
      breast cancer patients receiving chemotherapy.
AB  - The current study was to evaluate soluble ST-2 level and left ventricular
      ejection fraction (LVEF) in patients with breast cancer receiving doxorubicin or
      trastuzumab treatment for 6 months and determine whether soluble ST-2 level can
      be used to predictive left ventricular function impairment.Patients who were
      diagnosed as having breast cancer receiving doxorubicin or trastuzumab or
      combined therapy were enrolled. Demographic data, prior medical history and
      related medical therapy, and site and stage of breast cancer information were
      collected from electronic health record. Fasting blood was used to detect soluble
      ST-2 and brain natriuretic peptide (BNP) levels before and after 6 months
      doxorubicin or trastuzumab therapy. Echocardiography was performed before and
      after 6 months of doxorubicin or trastuzumab therapy.Participants were divided
      into 3 groups based on tertiary soluble ST-2 level. Compared with 1st tertiary
      group, patients in the 3rd tertiary group had higher proportion receiving
      combined therapy (14.3% vs 4.7%, P < .05). Baseline soluble ST-2 level was
      similar across groups. After 6 months' therapy, soluble ST-2 level was
      significantly higher in the 3rd tertiary group. Pearson correlation analysis
      showed that soluble ST-2 level was positively correlated with left ventricular
      volume and E/e' ratio while negatively correlated with LVEF. Doxorubicin,
      trastuzumab, combined therapy, soluble ST-2 level, and angiotensin-converting
      enzyme inhibitor/angiotensin receptor blocker treatment were all independently
      associated with LVEF change.In breast cancer patients receiving doxorubicin or
      trastuzumab therapy, soluble ST-2 level can be used to predict cardiac function
      and structure changes.

PMID- 30235731
TI  - Adherence to the dietary approaches to stop hypertension diet and risk of stroke:
      A meta-analysis of prospective studies.
AB  - The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to lower
      the risk of hypertension, but its role in the prevention of stroke remains in
      debate. We therefore conducted a meta-analysis to examine the association between
      DASH diet and incident stroke.A systematic database search in PubMed and Embase
      was performed to identify eligible prospective studies. The study-specific
      relative risks (RRs) and 95% confidence intervals (CIs) were pooled using random
      effect meta-analysis. Dose-response relationship between DASH diet score and risk
      of stroke was also assessed.We included 12 prospective cohort studies comprising
      a total of 548,632 participants, with follow-up duration ranging from 5.7 to 24
      years. Compared with lower adherence, higher adherence to the DASH diet was
      related to a reduced risk of developing stroke (RR 0.88, 95% CI 0.83-0.93). Such
      a benefit of DASH diet seemed to be greater in the Asian than in the Western
      populations (P for interaction  = .037). Dose-response meta-analysis indicated a
      linear association of the DASH diet score with stroke (P for nonlinearity =
      .411), and each 4-points increment in the score conferred a risk reduction of 4%
      (RR 0.96, 95% CI 0.94-0.97) in total stroke events.Our findings suggest that
      higher adherence to the DASH diet is associated with a decreased risk of stroke.

PMID- 30235732
TI  - Evaluation of willingness to pay per quality-adjusted life year for a cure: A
      contingent valuation method using a scenario-based survey.
AB  - Cost-effectiveness is 1 of the most important factors in medicine reimbursement,
      and social willingness to pay (WTP) can provide evidence for the threshold of
      cost-effectiveness analysis. Recently, the concept of curative medicines has been
      introduced, so it is necessary to study their cost-effectiveness. This study
      aimed to estimate WTP per quality-adjusted life year (QALY) for a cure in the
      Korean general population.A total of 507 people from the general population,
      proportionally assigned by sex, age, and region, participated in face-to-face
      interviews. The contingent valuation survey was conducted with scenarios
      involving 4 EuroQol-5 dimensions (EQ-5D) with different health statuses. We
      assumed a treatment that moved the health status of each scenario to perfect
      health. WTP for 1 year of treatment was derived using a double-bounded format
      followed by open-ended answers. In the cure scenario, the post-treatment effect
      continued for a lifetime; in the non-cure scenario, the effect instantly stopped
      when treatment was terminated. Additionally, prolonged treatment effects lasting
      5 and 10 years were added. To identify the factors influencing WTP, a multi-level
      analysis was performed.WTP per QALY for the non-cure scenario was KRW 15
      million/QALY. For the cure scenario, WTP was 2.3 times higher (KRW 35
      million/QALY) than in the non-cure scenario. The results for the prolonged
      treatment effect scenarios were KRW 22 million/QALY and KRW 27 million/QALY,
      which are 1.4 and 1.8 times higher than the non-cure scenario, respectively. In
      all scenarios, the statistically significant factors affecting WTP per QALY were
      higher education, higher household income, and healthcare provider.This study
      revealed that WTP for a cure treatment was higher than that for non-cure; this
      higher WTP should be considered in future decision-making regarding curative
      treatments.

PMID- 30235733
TI  - Sevoflurane addiction due to workplace exposure: A case report and literature
      review.
AB  - RATIONALE: Anesthesiologists have a well-known increased risk of substance abuse.
      High-concentration of inhalation anesthetics in exhaled air of operating room
      personnel is detected. such secondhand exposure produces neurobiological
      sensitization to the reinforcing effects of inhalation anesthetics. PATIENT
      CONCERNS: An addictive young male anesthesiologist who was long-term abuse with
      sevoflurane after 4 years occupational exposure. A 28-year-old anesthesiologist
      on duty was found deeply sleep in the locker room and coved his nose with Gauze
      with high-concentration of sevoflurane. He was found addiction to sevoflurane
      second time. Several life-threatening incidents occurred including severe
      aspiration pneumonia. No other addiction was found in his history before he
      became severely dependent on sevoflurane. DIAGNOSES: A visual analog scale was
      employed to assess the severity of craving for sevoflurane and the Benzodiazepine
      Withdrawal Symptom Scale (BWSQ2)-scale was used to assess sevoflurane withdrawal
      syndrome(WS). INTERVENTIONS: First time an opened original sevoflurane container
      filled with water instead of sevoflurane was handed out for a minute in order to
      elicit craving and withdrawal symptom in five therapeutic single-sessions. Second
      time an opened original sevoflurane container filled with sevoflurane instead of
      water was used as his powerful cur-stimulus and also was handed out for a minute.
      OUTCOMES: After professional therapy and continuous surveillance he was
      rehabilitation and back to work. However, after three weeks he became addiction
      to sevoflurane again. He showed very sensitive to sevoflurane and switched to
      other career. LESSONS: This case emphasizes that secondhand exposure to
      inhalation anesthetics may be dangerous and increase the life-threatening
      professional risk to anesthesiologists, although identification of the
      responsible factor remains difficult. However, the safety of operating room staff
      should be aroused wide-spread social concern.

PMID- 30235735
TI  - Modified C-H flap for simultaneous nipple reconstruction during autologous breast
      reconstruction: Surgical tips for safety and cosmesis.
AB  - BACKGROUND: Reconstruction of the nipple-areolar complex is the final stage of
      breast reconstruction. Nipple reconstruction is usually performed several months
      after breast reconstruction, because simultaneous reconstruction is thought to be
      risky. Here, we introduce our experiences of 1-stage procedures with immediate
      reconstruction of the nipple-areolar complex during autologous breast
      reconstruction. METHODS: Between 2008 and 2015, 51 mastectomy patients underwent
      1-stage breast and nipple reconstruction. All cases were reconstructed
      immediately with autologous tissue for the breast mound. The patients were
      divided into 2 groups according to the method of nipple-areolar complex
      reconstruction. In group A, 23 cases were reconstructed with a classical C-H
      flap, also known as the Hammond flap. In group B, 28 cases were reconstructed
      with a modified C-H flap, which is the evolved form of the classical Hammond
      flap. The nipple-areolar complex was evaluated preoperatively, immediately
      postoperatively, and 1 year postoperatively. Postoperative complications were
      also evaluated. RESULTS: The mean projection of the reconstructed nipple
      decreased by approximately 50% in group A and 38% in group B during the
      postoperative 1 year. However, the reconstructed nipple width and areolar
      diameter did not show a significant change in either group. Group A showed 26% of
      complication rate and 17% of revision rate, whereas group B showed 11% of
      complication rate and 4% of revision rate. However, no major complications such
      as complete necrosis of the reconstructed nipple, were observed in any patients.
      CONCLUSION: The modified technique group showed superior results in terms of
      safety and cosmesis. With our modified C-H flap method, simultaneous breast and
      nipple reconstruction is safe and has satisfactory results.

PMID- 30235734
TI  - Complicated Meckel's diverticulum: Presentation modes in adults.
AB  - Complicated Meckel's diverticulum represents a common etiology of acute abdomen
      in children. However, this condition is less frequent in adults. We reviewed the
      records of adult patients who underwent the surgical removal of complicated
      Meckel's diverticulum between 2001 and 2017 at 2 tertiary French medical centers.
      We then analyzed the clinical characteristics, mode of presentation, and
      management for all patients.The Meckel's diverticulum was resected in 37 patients
      (24 males and 13 females). The mean patient age was 46.1 +/- 21.4 years. The most
      common clinical presentations of complicated Meckel's diverticulum were
      diverticulitis (35.1%, n = 13), small-bowel obstruction (35.1%, n = 13), and
      gastrointestinal bleeding (29.8%, n = 11) (anemia, n = 1; hematochezia, n = 10).
      Age distribution was significantly different (P = .02) according to the 3
      Meckel's diverticulum complications: patients with diverticulitis (P = .02) were
      statistically more frequently over 40 (P = .05), significantly older than
      patients with gastrointestinal bleeding who were more frequently <40 (P = .05).
      There was a preoperative diagnosis available for 15 of the 37 patients (40%). An
      exploratory laparoscopy was necessary to determine the cause of disease for the
      other 22 patients (60%). An intestinal resection was performed in 33 patients
      (89%) and diverticulectomy was performed in 4 patients (11%). There was
      heterotopic tissue found in only 6 patients (16%). Postoperative complications
      were as follows: 1 death by cardiac failure in a 92-year-old patient and 2
      patients with postoperative wound infections. The follow-up time was 3 to 12
      months.The correct diagnosis of complicated Meckel's diverticulum in adults is
      difficult due to the lack of specific clinical presentation. As a result,
      exploratory laparoscopy appears to play a central role in cases of acute abdomen
      with uncertain diagnosis.

PMID- 30235736
TI  - Clinical and radiologic analysis of on-demand use of etanercept for disease
      flares in patients with rheumatoid arthritis for 2 years: The RESUME study: A
      case-control study.
AB  - To reduce costs of biological disease-modifying antirheumatic drugs (bDMARDs), we
      evaluated the efficacy of repeated etanercept (ETN) discontinuation and
      restarting in rheumatoid arthritis (RA) patients in a case-control study.Thirty
      one bDMARD-naive RA patients with moderate to high disease activity received ETN
      until low disease activity (LDA) was achieved, after which ETN was discontinued.
      Upon flaring, ETN was readministered with observation every 2 months for 2 years,
      and radiographically evaluated in comparison with a historical control group
      treated continuously with ETN. Statistical methods including Fisher exact test,
      analysis of variance (ANOVA), Kruskal-Wallis test, multiple regression analysis,
      and Student t test were conducted as appropriate.Thirteen patients with
      inadequate response to ETN were withdrawn from the study, and 5 had no flare-up
      after ETN discontinuation. In the remaining 13 patients, ETN was used on-demand
      to maintain LDA. Multivariate analysis revealed that MTX was significantly
      correlated with ETN. All 13 patients achieved LDA at final follow-up. Although
      joint damage progressed in patients using ETN on-demand, structural damage
      progression in the on-demand group was not significantly different from that in
      controls.On-demand use of ETN for flaring reduced disease activity but not
      structural damage in 50% of patients (though not significantly). However,
      inhibition of joint damage was achieved in 50% of patients after 2 years,
      supporting on-demand use of ETN as a treatment option for patients with RA who
      cannot afford bDMARD or targeted synthetic DMARD therapy.

PMID- 30235737
TI  - Association between Mycobacterium avium complex lung disease and serum vitamin D
      status, antimicrobial peptide levels, and bone mineral density.
AB  - Vitamin D maintains calcium balance and has immunomodulatory effects. Only few
      studies have revealed the relationship between vitamin D and its associated
      factors in Mycobacterium avium complex (MAC) infection. This study aimed to
      investigate the effects of MAC infection on serum vitamin D, human cationic
      antimicrobial protein 18, its C-terminal 37 amino acid fragment (hCAP18/LL-37)
      levels, and bone mineral density (BMD).We enrolled 58 patients with MAC lung
      disease and 15 control participants. Serum 25-hydroxyvitamin D and hCAP18/LL-37
      levels were measured via enzyme-linked immunosorbent assay. Lastly, computed
      tomography scan density readings of the BMD of the thoracic and lumbar vertebral
      bones (Th4, Th7, Th10, and L1) were assessed.No significant differences in
      patient characteristics and serum vitamin D levels were observed. Patients with
      MAC lung disease had significantly low serum hCAP18/LL-37 levels (P = .049).
      Moreover, low BMD of the mean thoracic and lumbar vertebrae was observed (mean
      Th, P = .012; L1, P = .48, respectively). A higher prevalence of scoliosis (P =
      .031) was observed in the participants with low BMD compared with the control
      participants. Based on a multivariate analysis, patients with MAC lung disease
      had significantly lower body mass index [odds ratio (OR), 19.1; 95% confidence
      interval (CI), 2.0-419.0; P < .01] and vertebral BMD (OR, 12.4; 95% CI, 1.7
      160.6; P = .012) than control participants.Serum hCAP18/LL-37 level and BMD were
      significantly decreased in patients with MAC lung disease without relation to
      serum vitamin D level. The vitamin D-independent pathway might affect the waning
      of antimicrobial peptides and decrease in BMD.

PMID- 30235739
TI  - Choroid plexus papilloma presenting as an occipital mass with neck pain: Case
      report.
AB  - RATIONALE: Choroid plexus papillomas are rare benign central nervous system
      neoplasms arising from choroid plexus epithelium. They are most often located in
      the lateral ventricle, followed by the fourth and third ventricles and, rarely,
      in the cerebellopontine angle. PATIENT CONCERNS: We report an uncommon case of a
      17-year-old boy who presented with neck pain that had lasted for more than 1
      month, with accompanying pain and numbness in his upper extremities. His
      conditions included slight dizziness, nausea, diplopia, paresthesia, and an
      unsteady gait. Magnetic resonance imaging (MRI) showed huge cerebellopontine
      angle tumor that extended to the front medulla oblongata. DIAGNOSIS: Choroid
      plexus papilloma (WHO I) was diagnosed in this patient. INTERVENTIONS: The
      patient was referred for neurosurgical intervention. The very large neoplasm was
      subtotally resected. OUTCOMES: The symptoms of the patient were gradually
      alleviated after surgery and subsequent radiotherapy treatment, but
      unfortunately, follow-up of 2 years later revealed that the disease was recurrent
      and the young man passed away. LESSONS: Neck pain is related to many factors. The
      case provided an awareness of the origin of severe intracranial disease. It is
      mandatory to take a thorough clinical assessment with a holistic approach.

PMID- 30235738
TI  - Validation of RIFLE, AKIN, and a modified AKIN definition ("backward
      classification") of acute kidney injury in a general ICU: Analysis of a 1-year
      period.
AB  - The aim of this study was to validate Acute Kidney Injury Network (AKIN) and to
      develop a modified AKIN aimed at an improved classification of patients without
      baseline creatinine versus Risk, Injury, Failure, Loss of kidney function, and
      End-stage kidney disease (RIFLE) in general intensive care unit (ICU) patients.We
      retrospectively analyzed medical records of general ICU patients over a 1-year
      period. We compared the grading of severity as well as the prediction of
      mortality and renal replacement therapy by AKIN and RIFLE. Furthermore, a
      modified AKIN score was evaluated.A total of 321 patients were included. In 87%
      of cases, the 2 definitions classified patients in the concordant severity group.
      Higher scores of AKIN and RIFLE were associated with increased ICU- and 28-day
      mortality. Both definitions provided large receiver operating characteristics
      (ROC)-area under the curve (AUCs) for the prediction of mortality, which were
      comparable to the ROC-AUC of unclassified serum creatinine. Modification of the
      AKIN score with a "backward classification" of baseline creatinine based on its
      time course resulted in a higher AKIN score in 32 patients.RIFLE and AKIN
      definitions had a high concordance in staging the severity of acute kidney
      injury. There was a strong relationship between the stages and need for dialysis,
      ICU, and 28-day mortality. However, unclassified serum creatinine values were at
      least comparable. Standardized observation of the creatinine time course allows
      for "ex-post" AKIN-classification in a substantial number of patients with
      missing baseline creatinine values.

PMID- 30235740
TI  - Adverse events of high-dose tigecycline in the treatment of ventilator-associated
      pneumonia due to multidrug-resistant pathogens.
AB  - The off-label uses of tigecycline (TGC) to treat ventilator-associated pneumonia
      (VAP) have aroused worldwide concerns. The efficacy about TGC has been recently
      reported. However, the adverse events (AEs) remain controversial. Our study aims
      to analyze the safety of the high-dose (HD) regimens in the treatment of VAP due
      to multidrug-resistant (MDR) pathogens.The clinical data of 134 patients who were
      diagnosed with VAP from January 2013 to December 2015 in the NeuroScience Care
      Unit (NCU) were analyzed retrospectively. The incidence and the occurrence time
      of AEs, 28-day mortality, and the factors of clinical effectiveness were
      explored.A total of 54 patients received the standard dose group (SD), 69 in the
      HD, and 11 in the nonstandard HD group (NHD). Acinetobacter baumannii were the
      main pathogenic bacteria. There was no statistic difference in the incidence of
      AEs and the 28-day mortality among the 3 groups (P > .05). Total bilirubin (TBIL)
      increased significantly after SD of TGC treatment (P = .004). Liver dysfunction
      occurred the latest (10.83 +/- 7.08), not in the duration of HD group (9.63 +/-
      3.92), whereas in the SD group (13.00 +/- 7.57) and NHD group (12.64 +/- 3.70).
      Patients with septic shock, MODS, and higher APACHE II score were of high risk in
      mortality. The HD group was associated with higher clinical effective rate and
      bacteria clearance rate.HD TGC was relatively safe and tolerable in ICU patients.
      The risk of side effects was related to the TGC duration, although not increased
      as the dosage rose. Full course of the HD regimen was associated with better
      outcomes for the treatment of VAP patients, especially for the MDR gram-negative
      bacilli infection. Inappropriate antimicrobial treatment might lead to clinical
      treatment failure.

PMID- 30235741
TI  - Spinal paragangliomas: Surgical treatment and follow-up outcomes in eight cases.
AB  - Paragangliomas are neuro-endocrine tumors originating from the adrenal gland.
      They are usually benign and nonfunctioning, rarely seen in central nervous
      system. More than 90% of central nervous system paragangliomas are manifested as
      carotid and glomus jugulare tumors. Spinal paragangliomas are quite rare.The
      study was conducted through retrospective analysis of the files of the patients
      who had undergone surgery with pre-diagnosis of spinal intradural tumor between
      2011 and 2017 and diagnosed with paraganglioma.A total of 8 patients (4 females
      and 4 males) were included in the study. Mean age of the patients was 51.1 years
      (28-64). Time to admission was mean 6.5 months (3 weeks-24 months). Recurrence
      was not observed in 7 patients, 1 patient is being followed up due to residual
      tumor.Treatment may be achieved through recognizing malignant transformation in
      patients who were not diagnosed histopathologically. We consider that quality of
      life of the patients may be improved through this way.

PMID- 30235742
TI  - Correlation of gene polymorphisms of CD36 and ApoE with susceptibility of
      Alzheimer disease: A case-control study.
AB  - This research was aimed to explore correlation of gene polymorphisms of CD36 and
      ApoE with susceptibility of Alzheimer disease (AD).This study was a case-control
      study. Two hundred eleven AD hospitalized patients were selected as the AD group
      and 241 subjects were selected as the control group. PCR-RFLP was used to detect
      three loci (rs7755, rs3211956, and rs10499859) of CD36 gene and ApoE genotype.
      Chi-square test and univariate nonconditional logistic regression analysis were
      used to calculate the odds ratio (OR) and 95% confidence interval (95% CI). The
      haplotypes were constructed using SHEsis online software and the correlation
      between haplotypes and AD was analyzed. Meanwhile, differences of 3 alleles of
      ApoE and 6 genotypes (E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, E4/E4) were compared
      between AD and control groups.The frequencies of rs7755 genotype (chi = 10.780, P
      = .005) and allele (chi = 10.549, P = .001) were statistically different between
      2 groups. The genotype frequency of rs3211956 was statistically different between
      AD and control groups (chi = 10.119, P = .006). For the rs7755 locus, GG genotype
      (OR: 2.013, 95% CI: 1.098-3.699) was an independent risk factor for AD compared
      with AA genotype. In the dominant model, the risk to develop AD in AG/GG genotype
      was 1.686 times higher than AA genotype. For the rs3211956 locus, compared with
      TT genotype, GT genotype (OR: 0.536, 95% CI: 0.340-0.846) was a protective factor
      for AD after adjusting various physiological and biochemical factors. In the
      dominant model, the risk of GT/GG genotype to develop AD was reduced by 41.6%.
      For ApoE gene, the distribution differences of E2/E3 (chi = 9.216, P = .002),
      E3/E4 (chi = 7.728, P = .005), and E4/E4 had statistical significance between the
      2 groups. The frequencies of allele E2 (chi = 9.359, P = .002) and E4 (chi =
      13.995, P < .001) were statistically significant between AD and control
      groups.The rs7755 and rs3211956 loci polymorphisms of CD36 gene and genotype
      E2/E3, E3/E4, E4/E4 of ApoE gene, and E2 and E4 alleles were statistically
      related with AD.

PMID- 30235743
TI  - Treating acute fatty liver of pregnancy with artificial liver support therapy:
      Systematic review.
AB  - BACKGROUND: Acute fatty liver of pregnancy (AFLP) is a serious disease with high
      mortality. Recent data suggest that postpartum application of artificial liver
      support therapy (ALST) in AFLP management improves disease outcome. In current
      study, we tend to further evaluate whether the type, the timing, and the number
      of postpartum ALST sessions and other clinical factors including complications
      and liver and renal function will influence disease outcome in ALST era. METHODS:
      Medical records of 15 AFLP patients having postpartum ALST in our hospital from
      2010 to 2016 were first retrospectively reviewed. A systematic review and
      statistical analysis was then conducted with our cases and those having
      postpartum ALST reported in PubMed, Embase, Cochrane, and ClinicalTrials.gov till
      the end of June 2016. RESULTS: Nine relevant studies were identified in the
      public databases. A total of 104 cases were enrolled for analysis including 15
      cases from our hospital and 89 cases from the identified 9 studies. Univariate
      analysis revealed that 2 complications, postpartum hemorrhage and multiple organ
      dysfunctions (MODS), were associated with the outcome of AFLP patients undergoing
      postpartum ALST. Binary logistic regression analysis further indicated that MODS
      was the only independent factor affecting disease outcome. Surprisingly, factors
      including pre-ALST serum levels of total bilirubin and creatinine, the type and
      number of postpartum ALST sessions, time interval between delivery and ALST were
      unrelated to disease outcome. CONCLUSION: Current data suggest that postpartum
      ALST improves the outcome of AFLP patients but more properly designed experiments
      are needed to confirm this point. Our study further indicates that occurrence of
      MODS carries a bad prognosis even in ALST era. Our study provides valuable
      information on guiding the clinical application of postpartum ALST in AFLP
      management.

PMID- 30235744
TI  - Metal allergy in total-joint arthroplasty: Case report and literature review.
AB  - RATIONALE: Due to the low incidence and lack of effective diagnostic measures for
      the diagnosis of metal allergy in patients undergoing total joint arthroplasty
      (TJA), diagnosis relies mainly on the exclusion of other causes, in particular
      infection. It remains a relatively unpredictable and poorly understood cause of
      implant failure. At present, skin patch testing, leukocyte migration inhibition
      test (LMIT) and lymphocyte transformation tests (LTT) are being commonly used to
      assess metal hypersensitivity.This report presents both a case and literature
      review. PATIENT CONCERNS: A 61-year-old female patient experienced continuous
      swelling and pain in the right knee joint for 9 months after a right-side total
      knee arthroplasty (TKA). DIAGNOSES: We believe this is the case report of metal
      allergy in TKA. The following were the reasons for this. First, no definite
      symptoms of infection during revision arthroplasty were observed, but with
      obvious hyperplasia of synovium. Furthermore, a frozen biopsy revealed an
      extremely low neutrophil count, which was considered to be caused by chronic
      inflammation. Second, the results of repeated post-operation reexaminations
      indicate a clear increase in the number of eosinophils, while no bacteria were
      found in the tissue bacterial smear performed during the operation. Third,
      improvements were clearly observed in the patient following synovectomy, revision
      of the polyethylene insert and anti-anaphylactic treatment. INTERVENTIONS: The
      patient underwent synovectomy, revision of the polyethylene insert and anti
      anaphylactic treatment. OUTCOMES: The patient's right knee remained mildly
      swollen; however, the pain has been relieved significantly. The range of motion
      could achieve 0 degrees of extension and 90 degrees of flexion. LESSONS: No
      consensus has been reached about the best diagnostic criteria for this disease,
      and most physicians would consider it to be a possibility when other diseases
      including periprosthetic joint infection (PJI) have been excluded. Although this
      case followed the same course, the outcome following synovectomy and anti
      anaphylactic treatment further confirmed our hypothesis.

PMID- 30235746
TI  - Challenges in the surgical treatment of undiagnosed functional paragangliomas: A
      case report.
AB  - INTRODUCTION: Paragangliomas (PGs) or extra-adrenal pheochromocytomas are rare
      neuroendocrine neoplasms of ubiquitous distribution. Those that produce excess
      catecholamine are categorized as functional, and those that do not are
      categorized as nonfunctional. Although modern medical technology is becoming more
      widespread, there are still substantial risks of misdiagnosis or missed diagnosis
      of PGs. CASE PRESENTATION: A 38-year-old woman who lived in an autonomous region
      of inner Mongolia presented complaining of having experienced coughing for
      approximately the past month. Chest computed tomography (CT) and magnetic
      resonance imaging (MRI) revealed a lesion on the right side of thoracic vertebra
      5-8 of approximately 66 mm * 54 mm, and it was deemed to be a mediastinal tumor
      that required surgical treatment. The patient exhibited severe hemodynamic
      instability during the operation, resulting in substantial challenges and risks
      with regard to anesthesia management. CONCLUSION: When a patient is suspected
      having PG, whether the surgery should be continued or not depends on their
      overall condition and whether hemodynamic fluctuation can be controlled to within
      the normal range. Both are factors that should be considered during
      intraoperative management. Communication between the surgeon and anesthesiologist
      is necessary, in order to accurately assess the risks associated with the
      operation. The combination of central venous pressure and the Flotrac/Vigileo
      system may provide precise guidance for complementary liquid therapy and reduce
      cardiopulmonary complications. After the operation, hemodynamic changes should be
      monitored continuously in the intensive care unit, and vasoactive drugs are
      required to avoid postoperative hypotension. Dramatic hemodynamic changes are
      certainly a challenge for patients and anesthesiologists, regardless of their
      origin, and sufficient attention should be paid to avoid serious consequences.

PMID- 30235747
TI  - A delayed-onset intracranial chronic subdural hematoma following a lumbar spinal
      subdural hematoma: A case report.
AB  - RATIONALE: A spinal subdural hematoma (SDH) is rarely complicated with an
      intracranial SDH. We found only 7 cases of spontaneous concurrent lumbar spinal
      and cranial SDHs, in which lumbar symptoms occurred before head symptoms. PATIENT
      CONCERNS: We describe a 77-year-old man with spontaneous concurrent spinal and
      cranial SDHs, in whom the spinal SDH was identified 30 days before the
      intracranial chronic SDH. DIAGNOSIS: Magnetic resonance imaging showed a spinal
      SDH at L4/L5. There was no paralysis, and the patient was managed conservatively.
      About 30 days after the onset of back pain, he experienced tinnitus and visual
      hallucination. Brain computed tomography showed a chronic SDH and midline shift.
      INTERVENTIONS: Burr-hole evacuation was performed, and the patient's condition
      improved. OUTCOMES: At 5 months of follow-up, there was no recurrence of the
      spinal or intracranial SDH. LESSONS: It is important to consider the possibility
      of intracranial hemorrhage when a spinal SDH is identified.

PMID- 30235745
TI  - Characteristics of repaglinide and its mechanism of action on insulin secretion
      in patients with newly diagnosed type-2 diabetes mellitus.
AB  - This study aims to compare the effect of repaglinide and metformin among Chinese
      patients with newly diagnosed diabetes, and explore the possible mechanisms by
      which repaglinide alters insulin secretion.Sixty subjects with glycated
      hemoglobin (HbA1c) < 10.0% were randomly selected to receive repaglinide or
      metformin monotherapy for 15 weeks. Blood glucose levels, glycemic variability,
      beta-cell function, and first-phase insulin secretion were compared between these
      2 groups at baseline and at 15 weeks. Mouse insulinoma (MIN-6) cells were divided
      into 3 groups: low glucose, high glucose, and repaglinide 50 nm groups. Cells and
      cell culture mediums were collected at different timepoints. The expression of
      pericentrin (PCNT), F-actin, and insulin were tested with immunofluorescence and
      enzyme-linked immunosorbent assay.All glycemic parameters and variability indexes
      significantly decreased from baseline to 15 weeks, while no significant
      difference was found between these 2 groups at baseline or at 15 weeks.
      Furthermore, there was no significant difference found in fasting insulin and
      postprandial insulin at baseline and at 15 weeks, while homeostasis model
      assessment beta significantly increased. The first-phase glucose and insulin
      secretion of the intravenous glucose tolerance test improved in both groups,
      especially in the repaglinide group. Insulin, PCNT, and F-actin expression in MIN
      6 cells decreased after 15 minutes of stimulation with repaglinide, while no
      difference was observed at 2, 6, and 12 hours. The insulin levels of the cell
      medium in the repaglinide group remained significantly higher at all
      timepoints.This study manifests that repaglinide has a noninferiority effect on
      the glycemic parameters of Chinese patients with newly diagnosed diabetes, when
      compared with metformin. The PCNT-F-actin pathway plays an important role in the
      repaglinide regulation process of on-demand insulin secretion.

PMID- 30235748
TI  - A liver transplant recipient with possible bupivacaine-induced liver injury
      caused by intra-articular injection after total knee arthroplasty: A case report.
AB  - RATIONALE: Although the survival period of patients who undergo liver
      transplantation is improving due to advances in surgical techniques and medical
      treatment, there is a lack of detailed, sufficient data that compare the choice
      of anesthetic agent in post-liver transplant surgery to avoid liver injury.
      PATIENT CONCERNS: The authors describe acute liver injury observed in a 61-year
      old man who underwent liver transplantation surgery 13 years previously and who
      was on immunosuppressive therapy. The patient underwent bilateral total knee
      arthroplasty under general anesthesia, for which a total of 200 mg bupivacaine
      was injected into each knee after wound closure. Liver enzyme levels increased to
      more than 10 times the upper limit of normal after the conclusion of surgery and
      remained extremely high on postoperative day 1. DIAGNOSES: Clinical and
      laboratory findings were consistent with bupivacaine-induced liver injury. Intra
      articular administration of bupivacaine after total knee arthroplasty is a widely
      used intraoperative analgesic method and complications are rare; nevertheless,
      the risk for inadvertent delivery into the systemic circulation remains.
      INTERVENTIONS: Clinical presentations and hepatobiliary ultrasound examination
      allowed a conservative management. OUTCOMES: Serum liver enzyme levels normalized
      12 days after surgery, and the patient was discharged 22 days after surgery.
      LESSONS: Acute liver injury can lead to graft failure from late death after liver
      transplantation. Transplant recipients with long-term survival have the highest
      risk for anesthesia because of post-transplant complications, including diabetes,
      hypertension, and renal insufficiency. Clinicians should be aware that analgesic
      techniques and anesthetics may affect graft function.

PMID- 30235749
TI  - Adrenal relapse of primary central nervous system diffuse large B-cell lymphoma:
      A case report.
AB  - RATIONALE: Primary central nervous system lymphoma (PCNSL) is a rare form of non
      Hodgkin lymphoma with a dismal outcome. Most patients relapse in intracranial
      sites and <5% of patients relapse in extracranial sites. Here, we present the
      first case of PCNSL with an adrenal relapse. PATIENT CONCERNS: A 72-year-old
      woman, first presented 7 years ago with complaints of headache and dizziness.
      DIAGNOSES: Enhanced magnetic resonance imaging revealed the mass within the
      splenium of the corpus callosum. On histological examination, there was a diffuse
      growth pattern of neoplastic cells in the brain biopsy. Immunohistochemistry and
      flow cytometric analysis demonstrated that the neoplastic cells were of B-cell
      lineage. INTERVENTIONS: The patient underwent methotrexate-based chemotherapy and
      whole-brain radiotherapy after the initial diagnosis of primary central nervous
      system-large B-cell lymphoma (CNS-DLBCL). OUTCOMES: After 4 years of clinical
      remission, the patient was diagnosed with endometrial cancer. Interestingly, a
      radiological study following the treatment of endometrial cancer demonstrated a
      right adrenal mass, which was suspicious for malignancy. Morphologic examination
      and immunohistochemistry studies confirmed the diagnosis of diffuse large B-cell
      lymphoma. A fluorescent in situ hybridization panel for lymphoma showed
      rearrangement of Immunoglobulin heavy chain (IGH) and B-cell lymphoma 6 (BCL6),
      respectively, suggesting fusion of BCL6/IGH. Immunoglobulin kappa analysis
      demonstrated a common origin for the brain and adrenal lesions, which led to the
      final diagnosis of an adrenal relapse of CNS-DLBCL. LESSONS: PCNSL is a highly
      infiltrative neoplasm, particularly at relapse. To the best of our knowledge,
      this is the first case of CNS-DLBCL with adrenal relapse. Considering the poor
      outcome of CNS-DLBCL, molecular genetic studies should be done to identify a
      common origin for the primary and secondary lesion.

PMID- 30235750
TI  - Delayed bilateral facet dislocation at L4-5: A case report.
AB  - RATIONALE: Traumatic bilateral facet dislocation in the lumbar (L) spine has
      rarely been reported. All reported cases were presented with acute facet
      dislocation. However, we present the first case of delayed bilateral facet
      dislocation at L4-5. PATIENT CONCERNS: A 34-year-old woman presented with back
      pain after a head-on collision. The patient was treated conservatively for 3
      months with rigid orthosis and activity restriction. Even after this conservative
      treatment, she continued to suffer from persistent back pain that radiated down
      her left leg and a progressively kyphotic posture. DIAGNOSES: Initial imaging
      studies revealed a fracture of the left L5 superior articular process with a
      posterior ligament complex (PLC) injury. Subsequent radiographs showed the locked
      facet dislocation with kyphotic changes. INTERVENTIONS: The patient underwent
      surgical reduction and fusion, and the operative findings revealed the L4-5
      bilateral facet dislocation and rupture of the PLC at the index level. OUTCOMES:
      After surgical reduction and fusion at L4-5 by posterior interbody fusion, we
      achieved a satisfactory clinical outcome. LESSONS: Injury of the PLC in the lower
      lumbar region deserves careful attention for the development of sequelae. The
      anatomic transition from lordosis to kyphosis, in the lumbosacral region may be
      related to this type of injury.

PMID- 30235751
TI  - Predictive value of drain pancreatic amylase concentration for postoperative
      pancreatic fistula on postoperative day 1 after pancreatic resection: An updated
      meta-analysis.
AB  - BACKGROUND: Postoperative pancreatic fistula (POPF) is a potentially fatal
      complication following pancreaticoduodenectomy. Early prediction and exclusion of
      POPF may be highly advantageous to enhance patient outcomes, and accelerate
      recovery. In this meta-analysis, we sought to assess the prediction of drain
      pancreatic amylase concentration on postoperative day 1 (DPA1) for POPF. METHODS:
      By searching online databases up to April 2018, all researches mentioned DPA1 for
      detecting POPF were analyzed. STATA 12.0 was used to analyze pooled predictive
      parameters. RESULTS: Seventeen studies were finally analyzed including 4676
      patients in total. The pooled sensitivity and specificity of DPA1 were
      respectively 0.85 (95% CI: 0.71, 0.93), 0.80 (95% CI: 0.74, 0.85) to predict
      overall POPF, and 0.70 (95% CI: 0.53, 0.82), 0.88 (95% CI: 0.86, 0.90) to predict
      CR-POPF. If pretest probability was 50%, corresponding post-test (+) were
      respectively 81%, 86% for overall POPF and CR-POPF when DPA1 was above cutoffs,
      while the post-test (-) were respectively 16%, 26% when DPA1 was under cutoffs.
      In subgroup analysis, sensitivities of cutoff >5000 group, 1000< cutoff <5000
      group, and cutoff <1000 group were respectively 0.65 (0.43-0.82), 0.82 (0.71
      0.89), 0.87 (0.78-0.92); and specificities were respectively 0.88 (0.83-0.92),
      0.83 (0.77-0.88), 0.71 (0.62-0.79). Positive LR was 5.5 (3.4-8.8), 4.8 (3.4-6.7),
      and 3.0 (2.3-4.0) respectively. Negative LR was 0.40 (0.22-0.72), 0.22 (0.13
      0.37), and 0.19 (0.11-0.32) respectively. CONCLUSION: DPA1, which has good
      sensitivity and specificity, is useful for predicting overall POPF and CR-POPF,
      according to the present studies. Meanwhile, it should be cautious to apply
      because there is a wide range in cutoffs between different studies.

PMID- 30235752
TI  - Neutrophil-to-lymphocyte ratio predicts diagnosis and prognosis of idiopathic
      sudden sensorineural hearing loss: A systematic review and meta-analysis.
AB  - BACKGROUND: Chronic inflammation has been regarded as one of the causes of
      idiopathic sudden sensorineural hearing loss (ISSHL). Several individual studies
      have reported the association between neutrophil-to-lymphocyte ratio (NLR) and
      ISSHL. However, the findings have been inconsistent, and these data have not been
      systematically evaluated. Thus, we conducted this meta-analysis to further
      explore the predictive value of NLR on formation and prognosis of ISSHL. METHODS:
      A comprehensive literature search was performed to identify eligible studies
      based on PubMed, Embase, Web of Science, and China National Knowledge
      Infrastructure. The Standardized mean deviation (SMD) with its 95% confidence
      interval (CI) was applied to be the effect size estimate. RESULTS: A total 10
      papers with 15 retrospective case-control studies, which included 1029 ISSHL
      patients (the case group) and 1020 healthy people (the control group), were
      selected for the meta-analysis of the relationship between NLR and onset of
      ISSHL. The NLR levels in the case group were observed to be higher than the
      control group (SMD = 1.65, 95% CI = 1.20-2.09, P < .001). The pooled results did
      not significantly change by the subgroup analyses based on study region, baseline
      matching, and laterality. Moreover, 9 publications with 12 retrospective cohort
      studies, which included 590 recovered ISSHL patients and 438 unrecovered ISSHL
      patients, explored the association between NLR and ISSHL prognosis, and the
      combined data showed that the NLR value was much higher in unrecovered patients
      rather than recovered patients (SMD = 1.27, 95% CI: 0.62-1.92, P < .001). The
      subgroup analyses based on study region, laterality, type of steroid, medication
      administration, maintenance treatment, follow-up period, and definition of
      "recovered" further supported these results. CONCLUSION: The results of this meta
      analysis suggest that NLR might be a useful biomarker to determine the onset and
      prognosis of ISSHL.

PMID- 30235753
TI  - Interaction between NF-kappaB and AP-1 and their intracellular localization at
      labor in human late pregnant myometrial cells in vivo and in vitro.
AB  - Preterm birth (PTB) is the most important cause of neonatal morbidity and
      mortality next to congenital anomalies in the developed world. NF-kappaB and AP-1
      were reported to play an important role in parturition initiation. However, the
      interaction relationship between the 2 molecules in labor initiation has not yet
      been reported.This study aimed to investigate the interaction between NF-kappaB
      and AP-1 and their intracellular translocation during labor in human late
      pregnant myometrial cells (HLPMCs).Co-immunoprecipitation (Co-IP), Western blot
      analysis, immunohistochemistry (IHC), and immunocytofluorescence (ICF) techniques
      were applied to explore the interaction between NF-kappaB and AP-1 and the
      alteration in their intracellular localization before and after labor onset.The
      protein expression levels of NF-kappaBp65 and AP-1(c-jun) in the natural labor
      group were observed significantly higher than that in the non-labor group.
      Pearson's correlation analysis showed a positive correlation between the protein
      expression of NF-kappaBp65 and AP-1(c-jun). Interactions were found between the 2
      molecules in HLPMCs both in natural labor and non-labor group and were also found
      in primary culture HLPMCs before and after neuromedin B (NMB) stimulation. NF
      kappaBp65 and AP-1(c-jun) were localized mainly in the cytoplasm before labor
      onset or NMB stimulation and were translocated into the nucleus upon labor
      initiation and NMB stimulation.These results demonstrated that upregulated
      protein expression of NF-kappaBp65 and AP-1(c-jun), the enhanced interaction
      between the 2 molecules, and their translocation to nucleus might be correlated
      to labor initiation.

PMID- 30235754
TI  - Diagnostic accuracy of magnetic resonance-guided prostate biopsy and template
      guided transperineal saturation biopsy.
AB  - To compare the accuracy of magnetic resonance-guided prostate biopsy (MR-GPB) and
      template-guided transperineal prostate saturation biopsy (TTPSB).A total of 219
      patients with elevated prostate-specific antigen, abnormal digital rectal
      examination or ultrasound findings were enrolled. All patients underwent
      multiparametric magnetic resonance image (mpMRI). Patients with a Prostate
      Imaging Reporting and Data System (PI-RADS) score of 3 to 5 underwent MR-GPB
      using 2 to 5 biopsy cores and then immediately underwent an 11-region TTPSB.
      Patients with a PI-RADS score of 1 to 2 underwent TTPSB alone. We compared the
      detection rates for any cancer, clinically significant prostate cancer (csPCA),
      and the spatial distribution of missed csPCA lesions.Among the 219 cases, 66
      (30.1%) had a PI-RADS score of 1 to 2 on mpMRI. The detection rate of TTPSB in
      these patients was 9.1% (6/66). In total, detection rates for any cancer and
      csPCA were 48.9% (107/219) and 42.9% (94/219), respectively. Detection rates for
      any cancer (TTPSB 87/219, 39.7%; MR-GPB76/219, 34.7%, P = .161) and csPCA (TTPSB
      76/219, 34.7%; MR-GPB 72/219, 32.9%, P = .636) did not significantly differ
      between the 2 groups. The csPCA lesions missed by MR-GPB were most commonly
      located on the left (8.5%, 8/94) and right (9.6%, 9/94) sides of the urethra.MR
      GPB can reduce the rate of unnecessary prostate biopsies by approximately 30% and
      exhibits an efficacy comparable to TTPSB for the detection of any cancer and
      csPCA. Nevertheless, approximately 1/4 of csPCAs were missed by MR-GPB and were
      most commonly located on both sides of the urethra.

PMID- 30235755
TI  - Correlations between Modic change and degeneration in 3-joint complex of the
      lower lumbar spine: A retrospective study.
AB  - BACKGROUND: Modic changes (MCs) associated with low back pain (LBP) have been
      assessed in a few studies. It has been documented that patients with LBP have MCs
      in a specific segment, but the relationship between facet joint or disc
      degeneration and MCs is still disputed. Thus, we aimed to evaluate the
      correlation between MC and facet joint or disc degeneration using imaging.
      METHODS: Imaging data of patients were retrospectively analyzed at the Orthopedic
      Department of the First Affiliated Hospital of Nanchang from January 2014 to
      August 2017. MCs, facet joint degeneration, and disc degeneration in L3-S1 were
      evaluated by lumbar MRI. chi test and contingency correlation coefficient were
      used for the statistical analyses, and a P value < .05 was considered
      statistically significant. RESULTS: In the descriptive statistical analysis, MCs
      were found to have the highest incidence in the L4-5 segment. Type II MCs had a
      higher incidence than type I and type III MCs regardless of whether they were in
      the L3-4, L4-5, or L5-S1 segment. On one hand, MCs were more frequently
      distributed in grades 3, 4, and 5 of the degenerative lumbar discs regardless of
      whether they were in the L3-4, L4-5, or L5-S1 segment (P < .000, V: contingency
      coefficient >0); particularly, type II MCs were closely related to lumbar disc
      degeneration (P < .05, V > 0). On the other hand, MCs were more frequently
      distributed in grades 1, 2, and 3 of the degenerative lumbar facet regardless of
      whether they were in the L3-4, L4-5, or L5-S1 segment (P < .05, V > 0).
      Particularly, type II MCs were frequently distributed in grades 1, 2, and 3 of
      the facet joint in the L4-5 and L5-S1 segments (P < .05, V > 0). CONCLUSION: MCs
      are correlated with the grade of lumbar spine degeneration, including lumbar disc
      and facet joint degeneration. MCs, especially type II, frequently occurred in
      severe degeneration of the lumbar disc and facet joint. Thus, MC may be one of
      the manifestations of lumbar disc and facet joint degeneration.

PMID- 30235756
TI  - Case report on alimentary tract hemorrhage and liver injury after therapy with
      oseltamivir: A case report.
AB  - RATIONALE: Oseltamivir-induced alimentary tract hemorrhage and liver injury are
      rarely reported in children and adult individuals. In this study, we described
      the clinical features and outcomes of oseltamivir-induced alimentary tract
      hemorrhage and liver injury in a child. PATIENT CONCERNS: Here, we present a case
      of a 6-year-old Asian boy with hematemesis and elevated alanine aminotransferase
      (ALT) (80 U/L) and aspartate aminotransferase (AST) (69 U/L) levels on day 2 of
      oseltamivir administration. The presence of alimentary tract hemorrhage and liver
      injury was diagnosed. The ALT level reached 1931.3 U/L, accompanied by an
      increase in total bilirubin (TBIL) to 53.3 MUmol/L on day 15 after oseltamivir
      administration. Additional tests were performed to determine the presence of
      viruses that can cause hepatitis and autoantibodies, and the results from these
      tests were all negative. DIAGNOSIS: Drug-induced liver injury was considered.
      INTERVENTIONS: This patient was treated with compound glycyrrhizin and reduced
      glutathione and glucocorticoid. OUTCOMES: The liver enzymes recovered within 6
      weeks without any symptoms of liver-related diseases after treatment with
      glucocorticoid. This treatment therefore helps reduce ALT and TBIL levels and
      protects the liver from further injury. LESSONS: Oral oseltamivir is widely used
      to treat influenza and the adverse effects of this drug were mostly mild.
      However, clinicians should always be alert for oseltamivir-induced alimentary
      tract hemorrhage and liver injury when prescribing oseltamivir for children.

PMID- 30235757
TI  - Optimal timing of thymectomy in nonthymomatous myasthenia gravis patients in
      China: A prospective study.
AB  - INTRODUCTION: While thymectomy is a recommended therapy for patients with
      Myasthenia Gravis (MG), there is insufficient evidence of its benefits over other
      therapies in patients in China, specifically, or of the most optimal timing for
      the procedure. Thus, there remains a clinical need for the investigation of these
      questions. Therefore, it is important to compare the clinical efficacy of
      thymectomy plus oral prednisone, an immunosuppressant protocol with prednisone,
      or immunosuppressants alone. CONCLUSION: We propose here to prospectively assess
      822 cases of MG and 1886 medical records from individuals hospitalized at the
      First Affiliated Hospital of Guangzhou University of Chinese Medicine and follow
      them for 3 years. Inclusion criteria will include the following: a Myasthenia
      Gravis Foundation of America (MGFA) clinical classification between I and IV
      while on optimal anticholinesterase therapy with or without oral prednisone or
      immunosuppressive therapy, an MG history of longer than 3 years, being 18 to 60
      years of age, and positive testing for serum acetylcholine receptor antibodies
      (AchR-Ab). Both thymomatous-naive and non-naive participants will be included.
      The primary outcomes will be: mortality, frequency of myasthenic crises, MGFA
      classification, and changes to the required dose of prednisone and
      immunosuppressants. Based on these outcomes, we will evaluate the efficacy of
      thymectomy as well as oral drugs in managing patients with nonthymomatous MG. As
      of September 2017, this study has been approved by the ethics committee of the
      First Affiliated Hospital of Guangzhou University of Chinese Medicine and the
      Registration number is ChiCTR1800017564(Version1.0, September 8,2017).

PMID- 30235758
TI  - Efficacy and safety of Shenfu injection for patients with return of spontaneous
      circulation after sudden cardiac arrest: Protocol for a systematic review and
      meta-analysis.
AB  - BACKGROUND: Sudden cardiac arrest (SCA) is one of the most common critical
      illnesses encountered in clinical practice. Shenfu injection (SFI) has received
      extensive attention as an alternative therapy that can effectively maintain the
      autonomic circulation function after cardiopulmonary resuscitation. However, the
      mechanism of SFI is not yet fully understood. In addition, there has been no
      systematic review or meta-analysis of SFI in the treatment of patients with
      return of spontaneous circulation after SCA. Herein, we describe the protocol of
      a proposed study based on the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses guidelines that aims to systematically evaluate the efficacy
      and safety of SFI in patients with return of spontaneous circulation after SCA.
      METHODS: Two researchers will search 9 electronic databases (PubMed, Medline,
      Embase, Cochrane Library, Web of Science, China National Knowledge
      Infrastructure, Chinese VIP Information, Wanfang, and Chinese Biomedical
      Database) to identify all studies that meet the inclusion criteria and were
      published before July 2018. After information extraction and methodological
      quality evaluation, we will use Stata 13.0 software (STATA Corporation, College
      Station, TX, USA) to synthesize the data. The primary outcomes will be the
      survival rate and Glasgow Coma Scale. RESULTS: The data synthesis results will
      objectively illustrate the efficacy and safety of SFI in patients with return of
      spontaneous circulation after SCA. CONCLUSION: The findings will provide a
      reference for the use of SFI in the treatment of patients with return of
      spontaneous circulation after SCA. REGISTRATION: PROSPERO (registration number:
      CRD42018104230).

PMID- 30235760
TI  - Application of siemens SMART neuro attenuation correction in brain PET imaging.
AB  - Siemens SMART neuro attenuation correction (SNAC) is a new type of calculated
      attenuation correction (CAC) method. This article aimed to evaluate the effect of
      SNAC on the quantitative analysis of brain positron emission tomography (PET)
      imaging.Brain PET images of 52 healthy participants after reconstructed by SNAC
      and CT attenuation correction (CTAC) were analyzed qualitatively by visual
      analysis, and quantitatively by Scenium software to compare their contrast,
      signal-to-noise ratio (SNR) as well as the mean standardized uptake value
      (SUVmean) of different brain regions.Compared with CTAC, reconstruction of images
      by SNAC significantly reduced the SNR by 17.3% (P < .001), but not affected the
      contrast (P = .440). In addition, the SUVmean of different brain regions in
      images reconstructed by SNAC is increased, but still significantly correlated
      with that by CTAC (r = 0.988, P < .001), with a coefficient of R = 0.976 in
      linear regression analysis. Moreover, the mean percent difference of SUVmean
      between images reconstructed with SNAC and CTAC was 8.03% +/- 5.38%, varying
      significantly in the range of -7.56% to 75.31% among 10 different brain regions
      (F = 35.702, P < .001) and showed greater percent difference in the peripheral
      brain regions than in the mesial brain regions.Image reconstruction by SNAC has
      greater effect on quantitative analysis by increasing SUVmean of different brain
      regions to varying degrees, but has little influence on the brain PET image
      quality. Moreover, it simplifies examination process and reduces radiation dose,
      which is beneficial to pediatric patients as well as serial scans to monitor
      therapy.

PMID- 30235759
TI  - Analysis of current situation and influencing factor of medical disputes among
      different levels of medical institutions based on the game theory in Xiamen of
      China: A cross-sectional survey.
AB  - With continuous development of the Chinese health care system, the doctor-patient
      relationship is increasingly tense in recent years. China has witnessed a surge
      in medical disputes, including many widely reported violent riots, attacks, and
      protests in hospitals. This study aimed to help to theorize the doctor-patient
      relationship based on the game theory, and analyze the current situation and
      influencing factors for medical disputes among different hospitalsA total of 17
      hospitals were randomly selected in Xiamen city, including 8 tertiary hospitals
      and 9 secondary hospitals. All medical dispute cases, between 2012 and 2014, were
      collected through questionnaires. Multiple logistic regression analyses were used
      to identify risk factors associated with medical disputes.In total, 896 medical
      dispute cases happened in 2012 to 2014, 733 (81.8%) of which occurred in tertiary
      hospitals. Medical disputes mainly were reported in the departments of obstetrics
      and gynecology (24.9%). The main causation of medical disputes was improper
      communication (24.0%) in tertiary hospitals and lower therapeutic skills (43.7%)
      in secondary hospitals, respectively. The negotiated rate (91.4%) in secondary
      hospitals was significantly higher than the tertiary hospitals (54.8%). The
      patients' age, occupation and the doctor's medical location, professional title
      were the main risk factors for the occurrence of medical violence.Relationships
      between doctors and patients have become worse increasingly, whereas doctor
      patient disputes or conflicts and their compensation have aggrandized year by
      year. The game relationship of doctor-patient is noncooperation, dynamic, and
      incomplete information game, and the advantages of cooperation are far greater
      than the competition between doctors and patients. Therefore, we need to take
      targeted measures to prevent and control the medical disputes by establishing a
      harmonious doctor-patient relationship in different levels of medical
      institutions.

PMID- 30235761
TI  - Efficacy of concurrent chemoradiotherapy combined with nimotuzumab for low-risk
      T4 stage nasopharyngeal carcinoma: A pilot study.
AB  - BACKGROUND: The purpose of this study was to analyze the efficacy and safety of
      concurrent chemoradiotherapy combined with Nimotuzumab for low-risk T4 stage
      nasopharyngeal carcinoma (NPC). METHODS: This study included 49 low-risk T4 stage
      NPC patients treated with concurrent chemoradiotherapy plus Nimotuzumab. The IMRT
      doses were planning target volume (PTV) 70-72 Gy for gross disease in the
      nasopharynx, and 66-70 Gy for positive lymph nodes. The doses for high risk and
      low risk region PTV were 60-62 Gy and 54-56 Gy in 31-33 fractions. All patients
      received a chemotherapy program consisting of Cisplatin 100mg/m2, day 1, Q3w and
      were treated by Nimotuzumab (Nimotuzumab 200mg, iv, Qw). RESULTS: All 49 patients
      completed at least two cycles of chemotherapy and seven weeks of Nimotuzumab. The
      total efficiency of therapy was 100.0%. The 3-year overall survival (OS), distant
      metastasis-free survival (DMFS), local-regional control (LRC) and progression
      free survival (PFS) rates were 89.7%, 87.8%, 97.9% and 85.7%, respectively. No
      regional lymph node recurrence was detected. The most serious acute toxicity was
      mucositis, with prevalence of Grades 0 to IV being 0.0%, 57.1%, 34.7%, 8.2%, and
      0.0%, respectively. Late toxicity manifested as Grades I and II xerostomia in 32
      and 10 patients. CONCLUSION: In patients with low-risk T4 stage NPC, concurrent
      chemoradiotherapy combined with Nimotuzumab yielded an excellent local control
      rate, and the toxicities were mild and tolerable. Distant metastasis was the main
      cause of treatment failure.

PMID- 30235762
TI  - First familial limb-girdle muscular dystrophy 2L in China: Clinical, imaging,
      pathological, and genetic features.
AB  - Limb-girdle muscular dystrophy 2L (LGMD2L) is mainly characterized by late adult
      onset, atrophy of proximal muscles, chronic progressive and asymmetric weakness,
      accompanied by increased creatine kinase (CK) levels, dystrophic pathological
      changes and electromyography showing myogenic damage. To date, familial LGMD2L
      was reported in European countries and had not been reported in China.A careful
      investigation of the clinical manifestations, muscle performance imaging, biopsy,
      and target next-generation sequencing (NGS) technology was utilized to identify
      pathogenic genetic variants in a 4-generation pedigree that includes 6 affected
      individuals.The results revealed mild-to-moderate hypertrophy of bilateral
      gastrocnemii and slight weakness and atrophy in the proximal muscles of the lower
      limbs, with obviously increased serum creatine kinase levels. The symptoms were
      more serious in the male proband but were also observed in females. Obvious and
      symmetric atrophy and fat infiltration of posterior segments of the thigh was
      evident in muscle magnetic resonance imaging (MRI). The pathological changes
      included a small amount of atrophic and hypertrophic fibers, scattered
      necrotizing fibers, a small number of increased nuclei, inward migration, mild
      proliferation of interstitial connective tissue, and no inflammatory cell
      infiltration. The pathogenic allele was a c.220C > T mutation in the anoctamin 5
      (ANO5) gene.The LGMD2L family was characterized by mild chronic myopathy and
      bilateral gastrocnemius hypertrophy with obviously increased CK levels.
      Pathological changes included atrophy of fibers with interstitial connective
      tissues hyperplasia. The pathogenic allele was a c.220C> T mutation in the ANO5
      gene.

PMID- 30235763
TI  - Oral health status of adult heart transplant recipients in China: A cross
      sectional study.
AB  - Limited information on the oral health status of adult heart transplant
      recipients (HTRs) is known, and no available data exist in China. A prerequisite
      dental evaluation is usually recommended for patients' postorgan transplantation
      because lifelong immunosuppression may predispose them to infection spread.The
      aim of this study was to investigate the oral health status of Chinese adult HTRs
      and determine the association between oral health status and history of heart
      transplantation (HT).We carried out a cross-sectional study to collect clinical,
      demographic, socioeconomic, and behavioral data from 81 adult patients who
      received heart transplantation during 2014 to 2015 in China. Clinical
      examinations for the presence of dental plaque, dental calculus, dental caries,
      and periodontal health conditions were performed in a standardized manner by one
      trained examiner. Sociodemographic, socioeconomic, and behavioral data were self
      reported using questionnaires. The prevalence of the above conditions was
      compared with 63 age- and sex-matched controls. General liner regression analysis
      was used to assess associations between mean number of decayed, missing, and
      filled teeth (DMFT) and mean community periodontal index of treatment needs
      (CPITN) scores and history of heart transplant.Mean age of the HT group was 47.7
      +/- 12.2 years and men accounted for 69.1% of the sample. The overall median DMFT
      score in the HT group was 3 (1-5) and caries prevalence was 80.2%, which were
      similar to the control group (P > .05). The overall mean CPITN score of the HT
      group was 1.84, which was significantly higher than the control group (1.07, P =
      .001). Participants in the HT group had worse oral hygiene status and more teeth
      with probing depth >= 4 mm than controls (P = .043). Compared with participants
      who had no history of heart transplantation, HTRs presented worse periodontal
      health conditions (mean CPITN score, adjusted odds ratio (OR) = 1.39, 95%
      confidence interval (CI) = 1.12-1.71, P = .003) and similar dental caries status
      (DMFT score, adjusted OR = 0.58, 95% CI = 0.37-0.91, P = .058).Periodontal health
      status was positively associated with history of heart transplantation in Chinese
      adult HTRs.

PMID- 30235764
TI  - Effectiveness and limitations of an incident-reporting system analyzed by local
      clinical safety leaders in a tertiary hospital: Prospective evaluation through
      real-time observations of patient safety incidents.
AB  - The effectiveness of a hospital incident-reporting system (IRS) on improve
      patient safety is unclear. This study objective was to assess which implemented
      improvement actions after the analysis of the incidents reported were effective
      in reduce near-misses or adverse events.Patient safety incidents (PSIs), near
      misses and adverse events, notified to the IRS were analyzed by local clinical
      safety leaders (CSLs) who propose and implement improvement actions. The local
      CSLs received training workshops in patient safety and analysis tools. Following
      the notification of a PSI in the IRS, prospective real-time observations with
      external staff were planned to record and rated the frequency of that PSI. This
      methodology was repeated after the implementation of the improvement
      actions.Ultimately, 1983 PSIs were identified. Surgery theaters, emergency
      departments, intensive care units, and general adult care units comprised 82% of
      all PSIs. The PSI rate increased from 0.39 to 3.4 per 1000 stays in 42 months. A
      significant correlation was found between the reporting rate per month and the
      number of workshop-trained local CSLs (Spearman coefficient = 0.874; P = .003). A
      total of 24,836 real-time observations showed a statistically significant
      reduction in PSIs observed in 63.15% (categories: medication P = .044;
      communication P = .037; technology P = .009) of the implemented improvements
      actions, but not in the organization category (P = .094). In the multivariate
      analyses, the following factors were associated with the reduction in near misses
      or adverse events after the implementation of the improvement actions: "adverse
      event" type of PSI (odds ratio [OR], 3.67; 95% confidence interval [CI], 1.93
      5.74), "disussion group" type of analysis (OR, 2.45; 95% CI, 1.52-3.76), and root
      cause type of analysis (OR, 2.32; 95% CI: 1.17-3.90).The implementation of a
      hospital IRS, together with the systematization of the method and analysis of
      PSIs by workshop-trained local CSLs led to an important reduction in the
      frequency of PSIs.

PMID- 30235765
TI  - Characteristics of heart rate variability in women with polycystic ovary
      syndrome: A retrospective cross-sectional study.
AB  - We aimed to compare the modulation of the autonomic nervous system (ANS) in women
      with polycystic ovary syndrome (PCOS) with that in healthy ovulatory women on the
      basis of heart rate variability (HRV), and to analyze the characteristics of the
      ANS in PCOS.In a retrospective chart review, HRV, body mass index, and physical
      examination data in women with PCOS and those with regular menstrual cycles were
      collected. Approval from the institutional review board (IRB) was obtained (IRB
      No. 2017-05-007-001) for this study. The mean outcomes were the values of HRV in
      the time [standard deviation of all normal R-R intervals (SDNN), the square root
      of the sum of the squares of the differences between the adjacent normal R-R
      intervals (rMSSD), and the mean heart rate turbulence (mean HRT)] and frequency
      [total power (TP), very-low-frequency power (VLF), low-frequency power (LF),
      normalized low-frequency power (LF norm), high-frequency power (HF), normalized
      high-frequency power (HF norm), and LF/HF ratio] domains. Differences between the
      2 groups were analyzed by Mann-Whitney U test, using SPSS for Windows (version
      22.0).There was no significant difference in the values of the time domain (SDNN,
      rMSSD, and mean HRT) between the groups. In the frequency domain, women with PCOS
      showed significantly higher LF (598.63 +/- 94.38 vs 459.13 +/- 163.64, P = .028),
      LF norm (48.64 +/- 3.39 vs 36.49 +/- 2.82, P = .009), and LF/HF ratio (1.49 +/-
      0.31 vs 0.73 +/- 0.13, P = .009) than the control group. HF norm was
      significantly lower in the women with PCOS than in the controls (51.38 +/- 3.39
      vs 63.51 +/- 2.82, P = .009). The TP, VLF, and HF showed no significant
      difference between the groups.The results of the present study indicated that
      PCOS is related to increased sympathetic modulation in HRV.

PMID- 30235766
TI  - Heterogeneity analysis of triphasic CT scan perfusion parameters in differential
      diagnosis of hepatocellular carcinoma and hemangioma.
AB  - This study is to investigate quantitative measures and heterogeneity of perfusion
      parameters in the differential diagnosis of hepatocellular carcinoma (HCC) and
      hemangioma.In total, 32 HCC and 44 hemangioma (types 1, 2, and 3) cases were
      included in this retrospective study. Hepatic artery coefficient (HAC), portal
      vein coefficient (PVC), and arterial enhancement fraction (AEF) were calculated.
      Tumor heterogeneity was analyzed. Perfusion parameters and corresponding
      percentiles were compared between the HCC and hemangioma (especially atypical
      hemangioma) cases, as well as between the substantial lesion part and surrounding
      normal tissue.The mean value, and the 10th, 50th, 75th, and 90th percentiles of
      PVC were significantly lower in the HCC cases than the types 1 and 2 hemangioma
      cases (P < .01). Moreover, the 90th percentile PVC in the HCC cases was also
      significantly lower than the type 3 hemangioma case (P < .01), while the mean
      value, and all the percentiles of AEF in the HCC cases were higher than the types
      2 and 3 hemangioma cases (P < .01). The 10th percentile HAC in the HCC cases was
      higher than the type 2 hemangioma cases (P < .05). The mean value, and the 10th
      and 50th percentile HAC in the HCC cases were higher than the type 3 hemangioma
      case (P < .05). However, there was no statistically significant difference in HAC
      between the HCC and type 1 hemangioma cases (P > .05).Quantitative measurement of
      perfusion parameters and heterogeneity analysis show significance differences in
      the early detection and differential diagnosis of HCC and hemangioma cases, which
      might contribute to increasing the diagnostic accuracy.

PMID- 30235768
TI  - Medical evacuation from abroad of critically ill patients: A case report and
      ethical issues.
AB  - RATIONALE: Patients repatriated from foreign hospitals are sources of extensively
      drug-resistant (XDR) bacteria outbreaks. Thus, an individual benefit potential
      for the patient opposes a collective ecological risk potential. These ethical
      issues have not been well studied. PATIENT CONCERNS: We report the case of a 74
      year-old patient repatriated from Mauritius to the French island of Reunion who
      presented mesenteric infarction evolving over several days, and who suffered a
      cardiac arrest before transfer. DIAGNOSES: In Reunion Island, a CT-scan revealed
      a multisegmental enlarged parietal enlargement associated with free peritoneal
      effusion and a suboccluded aspect of the superior mesenteric artery.
      INTERVENTIONS: Surgical exploration showed a severe mesenteric infarction with
      peritonitis, and a resection of 120cm of the small intestine was conducted. This
      patient was infected with a vanA glycopeptide-resistant Enterococcus faecium and
      a carbapenem-resistant Klebsiella pneumoniae which produced carbapenemases NDM-1
      and OXA-181, which required specific care and could have led to a local epidemic.
      OUTCOMES: The patient died after 9 days after being admitted to the ICU. LESSONS:
      Repatriation of critically ill patients from abroad should be considered
      according to ethical criteria, evaluating, if possible, the expected benefits,
      and ecological risks incurred. Limiting unnecessary transfers could be an
      effective measure to limit the spread of XDR bacteria.

PMID- 30235767
TI  - Detection of seizure patterns with multichannel amplitude-integrated EEG and the
      color density spectral array in the adult neurology intensive care unit.
AB  - This study's purpose was to determine the sensitivity, false-positive and false
      negative of seizure detection in adult intensive care by amplitude-integrated
      electroencephalography (aEEG) and color density spectral array (CDSA).30
      continuous electroencephalogram (EEG) recordings were randomly performed in 3
      digital EEG-recording machines, 3 specialized neurophysiologists participated in
      this study, underwent 4 hours of training of CDSA and aEEG, marked any epochs
      suspected to be seizures without access to the raw EEG. The results will be
      compared and analyzed with continuous EEG reading to consider sensitivity,
      positive or negative rate.The recordings in this study, comprised 720 hours of
      EEG containing a total of 435 seizures. The median sensitivity for seizure
      identification was 80% of CDSA and 81.3% of aEEG, Median false-positive was 4 per
      24 hours of CDSA, and 2 per 24 hours of aEEG display, Median false-negative was 4
      per 24 hours of CDSA, and 4 per 24 hours of aEEG display. The time spent in
      identification of seizures by CDSA and aEEG was much time-saving than continuous
      EEG-reading.In this study, both CDSA and aEEG have a higher sensitivity but lower
      false-positive or missed rate in the interpretation of seizure identification in
      adult NICU.

PMID- 30235769
TI  - Management of calcific myonecrosis with a sinus tract: A case report.
AB  - RATIONALE: Calcific myonecrosis is a very rare late sequela that occurs in
      patients who have had trauma accompanied by vascular compromise, in which a
      single muscle or entire muscles in a compartment undergoes necrosis and form a
      calcified mass. It is mostly a benign entity, but some cases cause bone
      destruction and form non-healing chronic sinuses. In such cases, wound management
      becomes difficult and there is a potential risk of secondary infection. PATIENT
      CONCERNS: A 60-year-old male was referred for evaluation of a pain, erythematous
      changes, and draining sinus of the anterolateral aspect of his left leg. He had
      an open reduction and internal fixation as well as a stent insertion in the
      femoral artery owing to a distal femur fracture and femoral artery rupture.
      DIAGNOSES: A thick fluid with a chalk-like material was discharged through the
      shiny skin via the sinus. The radiographs of the left leg showed a large,
      fusiform-shaped, radiopaque soft tissue mass in the space between the tibia and
      fibula. We performed an incisional biopsy to differentiated soft tissue sarcoma
      and malignant cells were found. Pathologic evaluation revealed acute and chronic
      inflammation with dystrophic calcification. These findings led to the diagnosis
      of calcific myonecrosis. INTERVENTIONS: We performed an extensive debridement of
      the anterior and deep posterior compartments to ensure definitive treatment. Upon
      performing extensive debridement, we inserted a drain tube and performed primary
      closure. OUTCOMES: The fluid continued to be discharged through the drain even
      after the surgery; delayed wound healing occurred 4 weeks following the surgery,
      and there was no recurrence at follow-up conducted 2 years later. LESSONS:
      Calcific myonecrosis is mostly a benign entity, but some cases of calcific
      myonecrosis cause bone destruction and form non-healing chronic sinuses. In such
      cases, surgical treatment is required, during which the necrotic tissue and
      calcific material must be extensively debrided and drained.

PMID- 30235770
TI  - Risk factors for renal involvement and severe kidney disease in 2731 Chinese
      children with Henoch-Schonlein purpura: A retrospective study.
AB  - To identify the risk factors for developing renal involvement and severe kidney
      disease in Chinese childhood Henoch-Schonlein purpura (HSP) patients.This was a
      retrospective study of 2731 children with HSP diagnosed between 2012 and 2015. We
      analyzed their demographic data, clinical manifestations, and laboratory tests
      retrospectively. Multivariate logistic regression analysis was used to assess the
      risk factors.Renal involvement occurred in 844 HSP patients (35.60%), and severe
      kidney disease occurred in 104 HSP patients (4.39%). Age over 6 years old at
      onset, colder season, more than 8 days interval between symptom onset and
      diagnosis, residence in rural, recurrence, angioedema, and the central nervous
      system (CNS) involvement were the significant risk factors for renal involvement.
      At the same time, age over 6 years at onset, more than 8 days interval between
      symptom onset and diagnosis, recurrence, angioedema, and CNS involvement were
      highly associated with severe kidney disease. Angioedema, longer interval between
      symptom onset and diagnosis, older age at HSP onset, and recurrence are
      prognostic indicators for renal involvement and severe kidney disease in children
      with HSP. The onset in colder season and rural residence associated with an
      increased risk for renal involvement, and the CNS involvement had an increased
      risk for severe kidney disease.HSP tends not to be self-limiting, and could
      progress into renal involvement or severe kidney disease for some of the HSP
      patients. Pediatricians should pay more attention to the children diagnosed with
      HSP, who also have these risk factors, for potential to develop renal
      involvement, and severe kidney disease, especially.

PMID- 30235772
TI  - The diagnostic accuracy of fluorodeoxyglucose-positron emission
      tomography/computed tomography and sentinel node biopsy in the prediction of
      pelvic lymph node metastasis in patients with endometrial cancer: A retrospective
      observational study.
AB  - According to the sentinel node biopsy (SNB), systematic pelvic lymph node
      dissection (PLND) may not be needed for patients with early-stage endometrial
      cancer. On the other hand, imaging technology including fluorodeoxyglucose
      positron emission tomography/computed tomography (FDG PET/CT) has been developing
      worldwide. The aim of this study was to evaluate the combined diagnostic accuracy
      of FDG PET/CT and SNB in the prediction of pelvic lymph node metastasis in
      endometrial cancer patients.One hundred twenty-one patients with endometrial
      cancer underwent FDG PET/CT before hysterectomy and received SNB followed by
      systematic PLND. Univariate and multivariate analyses were performed to compare
      the diagnostic accuracy of FDG PET/CT and SNB in the prediction of pelvic node
      metastasis to the ultimate histologic status.FDG PET/CT had lower sensitivity
      (36.8% versus 57.9%, P = .1) and a higher specificity (96.4% versus 84.8%, P <
      .01) than SNB. The kappa statistics of FDG PET/CT and SNB were 0.37 (95% CI, 0.15
      0.59) and 0.72 (95% CI, 0.53-0.90), respectively. The sensitivity of SNB was
      significantly higher than that of FDG PET/CT in all hemi-pelvises (HPs) in which
      the short axis of the largest metastatic lymph node was <5 mm in diameter (72.7%
      versus 18.2%, P = .01). In contrast, the sensitivity of FDG PET/CT was higher
      than that of SNB in all HPs in which the short axis of the largest metastatic
      lymph node was >=5 mm in diameter (62.5% versus 37.5%, P = .2); however, the
      difference was not statistically significant. When the combined diagnosis of FDG
      PET/CT and SNB was made, the sensitivity and specificity were 84.2% and 82.1%,
      respectively.SNB was more useful for detecting lymph node metastasis than FDG
      PET/CT, especially in patients with small metastatic lymph nodes. The combined
      diagnosis of FDG PET/CT and SNB improves the sensitivity; PET-positive nodes
      should be dissected regardless of SNB status and HPs in which SNB was not
      detected should be dissected systematically regardless of FDG PET/CT status.

PMID- 30235771
TI  - The role of dual time point PET/CT for distinguishing malignant from benign focal
      18F-FDG uptake duodenal lesions.
AB  - The aim of this study was to evaluate the diagnostic criteria of dual time point
      Fluorine-18 fluorodeoxyglucose (F-FDG) positron emission tomography/computed
      tomography (PET/CT) in differentiating malignant from benign focal hypermetabolic
      lesions of duodenum.A total of 50 patients underwent F-FDG PET/CT at 2 points: 60
      +/- 13.7 minutes (early imaging) and 120 +/- 26.4 minutes (delayed imaging) after
      tracer injection. Early maximum standardized uptake value (SUVE), delayed maximum
      standardized uptake value (SUVD), difference between early and delayed maximum
      standardized uptake value (D-SUVmax), and retention index (RI) were calculated
      for each duodenal lesion. Receiver operating characteristic analysis (ROC) was
      performed to evaluate the discriminating validity of the parameters.There were 32
      malignant and 18 benign focal F-FDG uptake duodenal lesions. The values of SUVE,
      SUVD, and D-SUVmax were significantly different between malignant and benign
      lesions (12.5 +/- 6.3 vs 5.8 +/- 1.2, 13.5 +/- 6.5 vs 5.5 +/- 1.1 and 0.3 +/- 0.8
      vs 1.0 +/- 1.0, respectively). The areas under the curves (AUCs) of SUVE, SUVD, D
      SUVmax were 0.932, 0.964 and 0.707, respectively. There was no significantly
      difference between SUVE and SUVD based on AUC. In detecting malignant lesions,
      SUVE=6.9 yielded a sensitivity of 88.9% and specificity of 84.4%, SUVD=7.2
      yielded a sensitivity of 94.6% and specificity of 90.6%, D-SUVmax=0.5 yielded a
      sensitivity of 72.2% and specificity of 68.8%. SUVD was the best diagnostic
      indicator, regarding specificity and specificity.SUVE and SUVD had good
      sensitivity, specificity for differentiating duodenal lesions. But there was no
      significantly difference between diagnostic value of SUVE and SUVD. F-FDG uptake
      patterns are helpful for differentiating benign and malignant duodenal lesions.

PMID- 30235773
TI  - Higher pretreatment lactate dehydrogenase concentration predicts worse overall
      survival in patients with lung cancer.
AB  - BACKGROUND: The aim of this study was to systematically evaluate the prognostic
      role of pretreatment lactate dehydrogenase (LDH) concentration for survival in
      patients with lung cancer through performing a meta-analysis. METHODS: PubMed,
      EMBASE, Cochrane Library, Web of Science, and China National Knowledge
      Infrastructure were searched for potentially relevant literature. The study and
      patients' characteristics were extracted. Hazard ratios (HRs) with 95% confidence
      intervals (95% CIs) were pooled to estimate the prognostic role of LDH in
      patients with lung cancer. RESULTS: Fourteen studies with 4084 patients were
      included. Higher pretreatment LDH concentration was significantly associated with
      an increased risk of overall mortality in patients with lung cancer (HR = 1.49,
      95% CI, 1.38-1.59). Subgroup analysis of studies also resulted in a significantly
      increased risk of mortality in patients with small cell lung cancer (SCLC, HR =
      1.54, 95% CI, 1.43-1.67) or nonsmall cell lung cancer (NSCLC, HR = 1.25, 95% CI,
      1.06-1.46), with high pretreatment LDH concentration. No significant between
      study heterogeneity was observed (I = 12.0%, P = .321). No significant
      publication bias was found (P = .352) in the meta-analysis. CONCLUSION: The
      results suggested that higher pretreatment LDH concentration was associated with
      worse overall survival in patients with lung cancer. The findings may assist
      future research on anticancer therapy by targeting LDH and help predict prognosis
      in lung cancer patients. However, high-quality studies are required to further
      research and support these associations. Moreover, confounding factors such as
      patient ethnicity and tumor type should be considered in future studies.

PMID- 30235774
TI  - Systematic meta-analysis of genetic variants associated with osteosarcoma
      susceptibility.
AB  - BACKGROUND: In the past decade, accumulated evidence has suggested that genetic
      variation is related to the pathogenesis of osteosarcoma. Although there are a
      large number of studies on the association between genetic variation and
      osteosarcoma, their results are inconsistent. To clarify these findings, we
      performed a systematic meta-analysis using allelic contrasts for each gene
      specific single nucleotide variants with all available data in the field of
      osteosarcoma. METHODS: The literature search for relevant studies was conducted
      in PubMed, Embase, and Cochrane databases. Pooled ORs and 95% CI values were
      calculated by the random-effects model using the Comprehensive Meta-analysis
      version 2.0 software package. Heterogeneity between studies was examined by the
      Cochran's Q-test. RESULTS: The 32 genome-wide case-control population-based
      studies, involving 15,336 study subjects (6924 cases and 8412 controls), were
      included in this meta-analysis. We analyzed 24 single nucleotide variants (SNVs)
      in 14 genes. We identified 12 SNVs in CTLA-4, IL-8, MDM2, PRCKG, RECQL5, TNF-a,
      TP53, XRCC3, and VEGF that correlated with osteosarcoma susceptibility. The
      average pooled odds ratio for the 9 risk alleles was 2.082 (range: 1.585 to
      3.262). These included CTLA-4 rs231775, CTLA-4 rs5742909, PRCKG rs454006, RECQL5
      rs820196, TNF-alpha rs1800629, TP53 rs1042522, XRCC3 rs861539, VEGF rs699947, and
      VEGF rs3025039. The average pooled odds ratio for the 3 protective alleles, IL-8
      rs4073, MDM2 rs1690916, and VEGF rs2010963, was 0.606 (range: 0.510-0.719).
      Publication bias was not observed among the studies reporting positively
      correlated SNVs. The pooled odds ratios for the SNVs that correlated with
      osteosarcoma risk showed homogeneity. CONCLUSION: Our results provide powerful
      information for tracking the most viable gene candidates. Further studies with
      larger multiethnicity populations and investigations of the potential biological
      roles of these genetic variants in osteosarcoma should be conducted.

PMID- 30235775
TI  - Epithelioid sarcoma arising from the temporal space: A case report.
AB  - INTRODUCTION: Epithelioid sarcoma is a malignant soft tissue tumor arising from
      mesenchymal tissue and usually occurs in the extremities. The tumor involving the
      head and neck region is extremely rare. We present radiologically well-documented
      case of an epithelioid sarcoma arising from the temporal space. CASE
      PRESENTATION: A 35-year-old woman presented with a slowly growing, painless
      palpable mass in the left temporal area. Ultrasound (US) revealed a lobulated
      hypoechoic mass with internal vascularity. On magnetic resonance (MR) imaging,
      the mass showed heterogeneous signal intensity with a central necrotic area and
      peritumoral infiltration. On the basis of the clinical and radiological
      characteristics, the lesion was considered to be a malignant tumor originating
      from soft tissue. An incisional biopsy was performed. The diagnosis of
      epithelioid sarcoma was based on microscopic examination and immunohistochemical
      analysis. F-fluorodeoxyglucose positron emission tomography/computed tomography
      (FDG-PET/CT) was used to stage the tumor and demonstrated intense FDG uptake in
      the mass without regional lymph node or distant metastasis. After the pathologic
      diagnosis of epithelioid sarcoma, the patient underwent total surgical resection
      of the tumor followed by postoperative irradiation. There was no evidence of
      recurrent disease during the follow-up period of 18 months. CONCLUSION: An
      epithelioid sarcoma should be considered in the differential diagnosis of a
      locally aggressive lesion occurring in the temporal space of head and exhibiting
      a heterogeneous appearance on imaging studies, including a central necrotic area
      and signal intensity suggestive of infiltration of soft tissue adjacent to the
      tumor. It is, however, true that head-and-neck involvement is very rare, and the
      radiological findings are not pathognomonic.

PMID- 30235776
TI  - Research on pseudo-CT imaging technique based on an ultrasound deformation field
      with binary mask in radiotherapy.
AB  - This study aimed to investigate the reliability of pseudo-computed tomography
      (pseudo-CT) imaging based on ultrasound (US) deformation fields under different
      binary masks in radiotherapy.We used 3-dimensional (3D) CT and US images,
      including those acquired during CT simulation positioning, and cone-beam CT
      (CBCT) and US images acquired 1 week after treating 3 patients with cervical
      cancer. Image data of 3 different layers were selected from the US images, and 3D
      CT images of each patient were selected. For US image registration, the following
      were created and applied: binary masks of the region of interest overlapping
      (ROIO) between the US image based on simulation positioning and US image for
      positioning verification, region of interest (ROI), whole overlapping (wholeO),
      and whole imaging region (whole). Accordingly, the deformation field was obtained
      and applied to CT images (CTsim), and different pseudo-CT images were acquired.
      Similarities between the pseudo-CT and CBCT images were compared, and
      registration accuracies between pseudo-CT images under different binary masks and
      CTsim were compared and discussed.A pair t test was conducted to normalized
      mutual information values of the registration accuracy between the pseudo-CT
      image based on ROIO binary mask and CTsim with other methods (P < .05), and the
      difference was statistically significant. A pair t test of normalized gray mean
      squared errors was also performed (P < .05), and the difference was statistically
      significant. The similarity function means between pseudo-CT, that is, based on
      ROIO, ROI, wholeO, whole, and no binary mask, and CBCT were 0.9084, 0.8365,
      0.7800, 0.6830, and 0.5518, respectively.Pseudo-CT based on ROIO binary mask best
      matched with CTsim and achieved the highest similarity with CBCT.

PMID- 30235777
TI  - Whole-body vibration exercise for low back pain: A meta-analysis protocol of
      randomized controlled trial.
AB  - BACKGROUND: Low back pain (LBP) affects about 80% of the population at some time
      in their lives. Exercise therapy is the most widely used nonsurgical intervention
      for low back pain in practice. Thus, whole-body vibration (WBV) exercise is
      becoming increasingly popular in relieving musculoskeletal pain and in improving
      function. However, the efficacy of WBV exercise is not without dispute for low
      back pain. This meta-analysis, with its comprehensive and rigorous methodology,
      will provide better insight into this problem. METHODS: Published articles will
      be identified using electronic searches from 1950 to 2018. The Cochrane Library,
      PubMed, Web of Science, Embase, CINAHL-Ebsco, PEDro, and China Biology Medicine
      will be searched for randomized controlled trials. Studies without a parallel
      comparison group will be excluded. Two reviewers will independently select
      relevant studies that investigate on WBV exercise for patients with LBP. Data
      extraction will be done independently by the same 2 reviewers who selected the
      studies. The primary outcome will be to assess pain, back-specific disability
      index, and adverse effect. Continuous data will be pooled by calculating the mean
      difference using the random-effects model. RESULTS: The results of the final meta
      analysis will provide an evidence of WBV exercise for low back pain. CONCLUSION:
      This meta-analysis will provide a detailed summary of the evidence on the effects
      of WBV exercise on patients with LBP, in comparison with general exercise or
      without treatment. This review will benefit to researchers and policy makers who
      are interested in the treatment of LBP by WBV exercise.

PMID- 30235779
TI  - Impact of reduced left ventricular function on repairing acute type A aortic
      dissection: Outcome and risk factors analysis from a single institutional
      experience: Erratum.

PMID- 30235780
TI  - Association between -174G>C polymorphism in the IL-6 promoter region and the risk
      of obesity: A meta-analysis: Erratum.

PMID- 30235778
TI  - Score for lung adenocarcinoma in China with EGFR mutation of exon 19: Combination
      of clinical and radiological characteristics analysis.
AB  - BACKGROUD: The biopsy samples might be the only tumor material available for
      testing the EGFR mutation status in some cases, but these samples are often
      composed of variable ratios of tumor to normal cells. In this study, we sought to
      build a scoring system to predict Epidermal growth factor receptor (EGFR) exon 19
      mutation in lung adenocarcinoma by clinical and radiological features. METHODS:
      Enrolled in this study were 601 patients with lung adenocarcinoma. Qualitative
      evaluation of the clinical and radiological features included 25 aspects.
      Statistical analysis was used to assess the association of these features between
      the EGFR wild type and exon 19 mutation, based on a clinical scoring system built
      by the statistical model and the experience of the radiologists. RESULTS: EGRF
      exon-19-mutation was associated with the female gender [odds ratios (OR), 2.573;
      95% confidence intervals (CI), 1.689-3.920], tumor maximum diameter (OR, 0.357;
      95% CI, 0.235-0.542), the absence of emphysema (OR, 0.202; 95% CI, 0.110-0.368),
      the absence of fibrosis (OR, 0.168; 95% CI, 0.083-0.339), and pleural retraction
      (OR, 2.170; 95% CI, 1.434-3.285). The clinical scoring model assigned 3 points to
      the female gender, 2 points to small tumor maximum diameter (<=34.5 mm), 2 to the
      absence of emphysema, 2 to the absence of fibrosis, and 1 to the presence of
      pleural retraction. CONCLUSIONS: The scoring system based on the statistical
      analysis of clinical and radiological features may be a new alternative to the
      prediction of EGFR mutation subtypes.

PMID- 30235781
TI  - The utility of FDG-PET/CT imaging in the evaluation of multicentric
      reticulohistiocytosis: A case report: Erratum.

PMID- 30235782
TI  - Anterior cervical discectomy and fusion versus hybrid surgery in multilevel
      cervical spondylotic myelopathy: A meta-analysis: Erratum.

PMID- 30235783
TI  - Partial molar pregnancy in the cesarean scar: A case report and literature
      review: Erratum.

PMID- 30235784
TI  - Bandwidth Enhancement and Frequency Scanning Array Antenna Using Novel UWB Filter
      Integration Technique for OFDM UWB Radar Applications in Wireless Vital Signs
      Monitoring.
AB  - This paper presents the bandwidth enhancement and frequency scanning for fan beam
      array antenna utilizing novel technique of band-pass filter integration for
      wireless vital signs monitoring and vehicle navigation sensors. First, a fan beam
      array antenna comprising of a grounded coplanar waveguide (GCPW) radiating
      element, CPW fed line, and the grounded reflector is introduced which operate at
      a frequency band of 3.30 GHz and 3.50 GHz for WiMAX (World-wide Interoperability
      for Microwave Access) applications. An advantageous beam pattern is generated by
      the combination of a CPW feed network, non-parasitic grounded reflector, and non
      planar GCPW array monopole antenna. Secondly, a miniaturized wide-band bandpass
      filter is developed using SCSRR (Semi-Complementary Split Ring Resonator) and DGS
      (Defective Ground Structures) operating at 3-8 GHz frequency band. Finally, the
      designed filter is integrated within the frequency scanning beam array antenna in
      a novel way to increase the impedance bandwidth as well as frequency scanning.
      The new frequency beam array antenna with integrated band-pass filter operate at
      2.8 GHz to 6 GHz with a wide frequency scanning from the 50 to 125-degree range.

PMID- 30235785
TI  - AMPK Activation Reduces Hepatic Lipid Content by Increasing Fat Oxidation In
      Vivo.
AB  - The energy sensor AMP-activated protein kinase (AMPK) is a key player in the
      control of energy metabolism. AMPK regulates hepatic lipid metabolism through the
      phosphorylation of its well-recognized downstream target acetyl CoA carboxylase
      (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG)
      content via the inhibition of ACC to cause inhibition of de novo lipogenesis and
      stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of
      FAO in vivo has been recently questioned. We generated a mouse model of AMPK
      activation specifically in the liver, achieved by expression of a constitutively
      active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that
      liver-specific AMPK activation is sufficient to induce a reduction in the
      respiratory exchange ratio and an increase in FAO rates in vivo. This led to a
      more rapid metabolic switch from carbohydrate to lipid oxidation during the
      transition from fed to fasting. Finally, mice with chronic AMPK activation in the
      liver display high fat oxidation capacity evidenced by increased [C14]-palmitate
      oxidation and ketone body production leading to reduced hepatic TG content and
      body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of
      lipid metabolism between the liver and adipose tissue.

PMID- 30235786
TI  - Cement Kiln By-Pass Dust: An Effective Alkaline Activator for Pozzolanic
      Materials.
AB  - Cement kiln by-pass dust (CKD) is a fine-grained by-product of Portland clinker
      manufacturing. Its chemical composition is not suitable for returning back into
      feedstock and, therefore, it has to be discharged. Such an increasing waste
      production contributes to the high environmental impact of the cement industry. A
      possible solution for the ecological processing of CKD is its incorporation into
      alkali-activated blast furnace slag binders. Thanks to high alkaline content, CKD
      serves as an effective accelerator for latent hydraulic substances which
      positively affect their mechanical properties. It was found out that CKD in
      combination with sodium carbonate creates sodium hydroxide in situ which together
      with sodium water glass content increases the dissolution of blast furnace slag
      particles and subsequently binder phase formation resulting in better flexural
      and compressive strength development compared to the sample without it. At the
      same time, the addition of CKD compensates the autogenous shrinkage of alkali
      activated materials reducing the risk of material cracking. On the other hand,
      this type of inorganic admixture accelerates the hydration process causing rapid
      loss of workability.

PMID- 30235787
TI  - Estimation of Arterial Carbon Dioxide Based on End-Tidal Gas Pressure and Oxygen
      Saturation.
AB  - Arterial blood gas (ABG) analysis is the traditional method for measuring the
      partial pressure of carbon dioxide. In mechanically ventilated patients a
      continuous noninvasive monitoring of carbon dioxide would obviously be
      attractive. In the current study, we present a novel formula for noninvasive
      estimation of arterial carbon dioxide. Eighty-one datasets were collected from 19
      anesthetized and mechanically ventilated pigs. Eleven animals were mechanically
      ventilated without interventions. In the remaining eight pigs the partial
      pressure of carbon dioxide was manipulated. The new formula (Formula 1) is PaCO2
      = PETCO2 + k(PETO2 - PaO2) where PaO2 was calculated from the oxygen saturation.
      We tested the agreements of this novel formula and compared it to a traditional
      method using the baseline PaCO2 - ETCO2 gap added to subsequently measured, end
      tidal carbon dioxide levels (Formula 2). The mean difference between PaCO2 and
      calculated carbon dioxide (Formula 1) was 0.16 kPa (+/-SE 1.17). The mean
      difference between PaCO2 and carbon dioxide with Formula 2 was 0.66 kPa (+/-SE
      0.18). With a mixed linear model excluding cases with cardiorespiratory collapse,
      there was a significant difference between formulae (p < 0.001), as well as
      significant interaction between formulae and time (p < 0.001). In this
      preliminary animal study, this novel formula appears to have a reasonable
      agreement with PaCO2 values measured with ABG analysis, but needs further
      validation in human patients.

PMID- 30235788
TI  - Analysis of Psychological Risks in the Professional Activities of Oil and Gas
      Workers in the Far North of the Russian Federation.
AB  - The professional activity in shifts in the Arctic contributes to the development
      of unfavorable functional status and destructive personal qualities of workers,
      which leads to a decrease in the level of mental health and efficiency of labor
      activity. The reference to the risk-oriented approach is conditioned by the need
      to predict the professional efficiency of shift personnel. The purpose of this
      study is to determine the psychological risks of oil and gas workers with a shift
      work organization in the Arctic. The study involved 70 oil and gas workers. The
      research methods were used as follows: documentation study, work process
      monitoring, questionnaire survey, psychophysiological and psychological testing,
      and statistical analysis methods: descriptive statistics-conjugacy tables with
      calculation of Pearson's criterion, two-stage cluster, dispersion, and
      discriminant analyzes. As a result of this research, it was established that oil
      and gas workers characterized by different combinations of character
      accentuations would have different psychological risks, and, consequently,
      different approaches to their psychological support are needed.

PMID- 30235790
TI  - MT-Feeding-Induced Impermanent Sex Reversal in the Orange-Spotted Grouper during
      Sex Differentiation.
AB  - In this study, we systematically investigated the process of sex reversal induced
      by 17-methyltestosterone (MT) feeding and MT-feeding withdrawal at the ovary
      differentiation stage in orange-spotted groupers, Epinephelus coioides. Gonadal
      histology showed that MT feeding induced a precocious sex reversal from immature
      ovaries to testes, bypassing the formation of an ovarian cavity, and MT-feeding
      withdrawal led to an ovarian fate. In both the MT feeding and MT-feeding
      withdrawal phases, cytochrome P450 family 11 subfamily B (cyp11b) gene expression
      and serum 11-KT levels were not significantly changed, suggesting that the MT
      treated fish did not generate endogenous steroids, even though active
      spermatogenesis occurred. Finally, by tracing doublesex-expressing and Mab-3
      related transcription factor 1 (dmrt1)-expressing cells and TUNEL (terminal
      deoxynucleotidyl transferase 2-deoxyuridine, 5-triphosphate nick end labeling)
      assays, we found that the efferent duct formed first, and then, the germ cells
      and somatic cells of the testicular tissue were generated around the efferent
      duct during MT-feeding-induced precocious sex reversal. Collectively, our
      findings provide insights into the molecular and cellular mechanisms underlying
      sex reversal induced by exogenous hormones during sex differentiation in the
      protogynous orange-spotted grouper.

PMID- 30235791
TI  - Broadband Microwave Absorbing Composites with a Multi-Scale Layered Structure
      Based on Reduced Graphene Oxide Film as the Frequency Selective Surface.
AB  - A broadband microwave absorbing composite with a multi-scale layered structure is
      proposed, in which a reduced graphene oxide (RGO) film sandwiched between two
      layers of epoxy glass fiber laminates serves as the frequency selective surface
      (FSS). RGO films with the desired electrical properties were synthesized directly
      by hydrothermal reaction, vacuum filtration, and heat treatment without
      subsequent processing. With the novel layer-by-layer structure ranging from micro
      to macro scale, the optimized composite exhibits excellent microwave absorption
      performance with a total thickness of 3.2 mm. Its reflection coefficient (RC) is
      less than -10 dB in the entire X and Ku band, reaching a minimum value of -32 dB
      at 10.2 GHz and an average RC of -22.8 dB from 8 to 18 GHz. Enhanced microwave
      absorption of the composites is achieved through the optimization of layer
      thickness in the sandwich structure to promote destructive interference. Improved
      impedance matching by the introduction of FSS along with the polarization and
      conduction loss of layered graphene films also contribute to the increased
      absorption.

PMID- 30235789
TI  - Protein Phosphatase (PP2C9) Induces Protein Expression Differentially to Mediate
      Nitrogen Utilization Efficiency in Rice under Nitrogen-Deficient Condition.
AB  - Nitrogen (N) is an essential element usually limiting in plant growth and a basic
      factor for increasing the input cost in agriculture. To ensure the food security
      and environmental sustainability it is urgently required to manage the N
      fertilizer. The identification or development of genotypes with high nitrogen
      utilization efficiency (NUE) which can grow efficiently and sustain yield in low
      N conditions is a possible solution. In this study, two isogenic rice genotypes
      i.e., wild-type rice kitaake and its transgenic line PP2C9TL overexpressed
      protein phosphatase gene (PP2C9) were used for comparative proteomics analysis at
      control and low level of N to identify specific proteins and encoding genes
      related to high NUE. 2D gel electrophoresis was used to perform the differential
      proteome analysis. In the leaf proteome, 30 protein spots were differentially
      expressed between the two isogenic lines under low N level which were involved in
      the process of energy, photosynthesis, N metabolism, signaling, and defense
      mechanisms. In addition, we have found that protein phosphatase enhances nitrate
      reductase activation by downregulation of SnRK1 and 14-3-3 proteins. Furthermore,
      we showed that PP2C9TL exhibits higher NUE than WT due to higher activity of
      nitrate reductase. This study provides new insights on the rice proteome which
      would be useful in the development of new strategies to increase NUE in cereal
      crops.

PMID- 30235792
TI  - Supplementing Oregano Essential Oil in a Reduced-Protein Diet Improves Growth
      Performance and Nutrient Digestibility by Modulating Intestinal Bacteria,
      Intestinal Morphology, and Antioxidative Capacity of Growing-Finishing Pigs.
AB  - This study investigated the effects of supplementing oregano essential oil (OEO)
      to a reduced-protein diet on growth performance, nutrient digestibility,
      intestinal bacteria, intestinal morphology, and antioxidative capacity of growing
      finishing pigs. Forty-eight barrows were randomly allotted to four treatments
      including normal-protein diet (NPD), reduced-protein, amino acid-supplemented
      diet (RPD), the same RPD supplemented with chlortetracycline (RPA), and RPD
      supplemented with OEO (RPO). The data showed that dietary OEO supplementation
      increased the average daily gain of pigs compared with NPD and RPD. The gain:feed
      in RPO- and NPD-fed pigs was higher than those in RPD- and RPA-fed pigs.
      Increased average daily feed intake and 10th-rib backfat thickness were detected
      in RPA-fed pigs. Pigs fed the RPO had higher apparent total tract digestibility
      (ATTD) of crude protein than those fed the other diets. The RPD and RPA
      treatments showed reduced counts of Lactobacillus spp. in ileal digesta of pigs.
      The RPA and RPO treatments also showed lower Escherichia coli counts in ileal
      digesta than the NPD and RPD treatments. Dietary OEO supplementation increased
      villous height of the jejunum and the ileal and plasma total antioxidative
      capacity of pigs. In conclusion, dietary OEO supplementation could improve the
      growth performance and nutrient digestibility of pigs by modulating intestinal
      bacteria, intestinal morphology, and antioxidative capacity.

PMID- 30235793
TI  - Hairless Canaryseed: A Novel Cereal with Health Promoting Potential.
AB  - Glabrous canaryseeds were recently approved for human consumption as a novel
      cereal grain in Canada and the United States. Previously, canaryseeds were
      exclusively used as birdseed due to the presence of carcinogenic silica fibers;
      therefore the nutritional value of the seeds has been seriously overlooked. Two
      cultivars of glabrous canaryseeds (yellow and brown) were created from the hairy
      varieties. They are high in protein compared to other cereal grains, and contain
      high amounts of tryptophan, an amino acid normally lacking in cereals, and are
      gluten-free. Bioactive peptides of canaryseeds produced by in vitro
      gastrointestinal digestion have shown antioxidant, antidiabetic, and
      antihypertensive activity. The seeds contain other constituents with health
      promoting effects, including unsaturated fatty acids, minerals, and
      phytochemicals. Anti-nutritional components in the seeds are comparable to other
      cereal grains. Because of their beneficial health effects, canaryseeds should be
      regarded as a healthy food and have immense potential as a functional food and
      ingredient. Further research is required to determine additional bioactive
      peptide activity and capacity, as well as differences between the yellow and
      brown cultivars.

PMID- 30235794
TI  - Photosystem II Is More Sensitive than Photosystem I to Al3+ Induced
      Phytotoxicity.
AB  - Aluminium (Al) the most abundant metal in the earth's crust is toxic in acid
      soils (pH < 5.5) mainly in the ionic form of Al3+ species. The ability of crops
      to overcome Al toxicity varies among crop species and cultivars. Here, we report
      for a first time the simultaneous responses of photosystem II (PSII) and
      photosystem I (PSI) to Al3+ phytotoxicity. The responses of PSII and PSI in the
      durum wheat (Triticum turgidum L. cv. 'Appulo E') and the triticale (X
      Triticosecale Witmark cv. 'Dada') were evaluated by chlorophyll fluorescence
      quenching analysis and reflection spectroscopy respectively, under control (-Al,
      pH 6.5) and 148 MUM Al (+Al, pH 4.5) conditions. During control growth conditions
      the high activity of PSII in 'Appulo E' led to a rather higher electron flow to
      PSI, which induced a higher PSI excitation pressure in 'Appulo E' than in 'Dada'
      that presented a lower PSII activity. However, under 148 MUM Al the triticale
      'Dada' presented a lower PSII and PSI excitation pressure than 'Appulo E'. In
      conclusion, both photosystems of 'Dada' displayed a superior performance than
      'Appulo E' under Al exposure, while in both cultivars PSII was more affected than
      PSI from Al3+ phytotoxicity.

PMID- 30235795
TI  - Air-Coupled Excitation of a Slow A0 Mode Wave in Thin Plastic Films by an
      Ultrasonic PMN-32%PT Array.
AB  - Ultrasonic non-destructive testing techniques (NDT) based on the application of
      guided waves are already used for inspection of plate-type structures made of
      various materials, including composite materials. Air-coupled ultrasonic
      techniques are used to test such structures by means of guided waves. The
      objective of this research was development and investigation of air-coupled
      excitation of a slow A0 Lamb wave mode in thin plastic films by a PMN-32%PT
      ultrasonic array. It is known that when the velocity of the A0 mode in the film
      is less than the ultrasound velocity in air no leaky wave is observed in a
      surrounding air. It opens new possibilities for NDT of composite structures. The
      influence of the airborne wave may be eliminated by 3D filtering in a wavenumbers
      frequency domain. A special filter and corresponding signals processing technique
      were developed in order to obtain directivity patterns and velocity maps of the
      waves propagating in all directions. The measured ultrasound velocity values
      prove that, with the proposed method, it is possible to excite a slow A0 Lamb
      wave mode and to separate it from other parasitic waves propagating in air.
      Measurements of the parameters of the slow A0 mode, such as the propagation
      velocity in the plastic film, may be applied for the material characterization.

PMID- 30235796
TI  - Green Transforming Metallurgical Residue into Alkali-Activated Silicomanganese
      Slag-Based Cementitious Material as Photocatalyst.
AB  - Silicomanganese slag is a solid waste in metallurgical industry and can be
      transformed into an alkali-activated silicomanganese slag-based cementitious
      material (ASSC) for the first time. The ASSC shows quite low electro-conductivity
      and can be raised dramatically by incorporated carbon black (CB) in the matrix of
      ASSC to create an electro-conductive alkali-activated silicomanganese slag-based
      cementitious-composite (EASSC), served as a low cost and environmentally-friendly
      photocatalyst for the removal of dye pollutant in the paper. The
      interrelationships of mechanical, optical, electroconductive, microstructural,
      and photocatalytic properties are evaluated. The network of CB plays a critical
      role in the electron transfers. The electrical conductivity of EASSC doped 4.5%
      CB drastically increases by 594.2 times compared to that of ASSC. The FESEM, XRD,
      and XPS results indicated that the EASSC with mean grain size about 50 nm is
      composed of amorphous calcium silicate hydrate (CSH), alabandite (alpha-MnS) and
      CB. The UV-vis DRS and PL exhibit that the absorption edges of electro-conductive
      alkali-activated silicomanganese slag-based cementitious-composite EASSC samples
      are gradually blue-shifted and the photoluminescence intensities progressively
      decrease with increasing CB content. The activities of photocatalytic degradation
      of basic violet 5BN dye are positive correlated to the electro-conductivities.
      The separation efficiency of photo-generated electron-hole pairs is enhanced due
      to the electron transfers from alpha-MnS to the network of CB. The photocatalytic
      degradation of dye pollutant belongs to the second order kinetics via a reaction
      mechanism of superoxide radical (*O2-) intermediate.

PMID- 30235797
TI  - Engineering Surface and Optical Properties of TiO2-Coated Electrospun PVDF
      Nanofibers Via Controllable Self-Assembly.
AB  - Understanding the effect of a porous TiO2 nanolayer on the optical scattering and
      absorption through electrospun fibers is of great importance for the design and
      development of advanced optical extinction materials. Based on electrospinning
      and controllable self-assembly techniques, pure electrospun poly(vinylidene
      fluoride) (PVDF) fibers and TiO2-coated ones with different self-assembly cycles
      were prepared. The effect of TiO2 self-assembly cycles on surface parameters,
      e.g., thickness, assembled content, and porosity of the TiO2 nanolayer were
      determined by scanning electron microscopy, thermogravimetric analysis, and
      Fourier transform infrared spectroscopy. With an increase in the self-assembly
      cycles, the TiO2-coated electrospun PVDF fibers presented rougher surfaces and
      greater average diameters. According to the characterized surface parameters, the
      effects of the controllable self-assembly on the optical refractive index,
      absorption index, and infrared extinction were investigated to increase the
      optical properties of electrospun PVDF fibers. The results indicated that an
      increase of almost 120-130 cm-1 in infrared extinction could be achieved through
      the controllable self-assembly with only 5.7 wt. % assembled TiO2 content. This
      is highly efficient when compared with other coating modes. We believe that this
      study could give some positive guidance in the design of TiO2-coated electrospun
      fibers for improving their surface and optical properties.

PMID- 30235798
TI  - Design of SnO2 Aggregate/Nanosheet Composite Structures Based on Function
      Matching Strategy for Enhanced Dye-Sensitized Solar Cell Performance.
AB  - Hierarchical SnO2 nanocrystallites aggregates (NAs) were prepared with a simple
      room temperature-based aqueous solution method followed by simple freeze-drying
      treatment. The as-prepared SnO2 NAs were subsequently combined with SnO2
      nanosheet-based structures from the viewpoint of a function-matching strategy,
      and under an optimized condition, a power conversion efficiency (PCE) of 5.59%
      was obtained for the resultant hybrid photoanode, a remarkable 60% enhancement
      compared to that of dye-sensitized solar cells (DSCs) fabricated with bare SnO2
      NAs architecture. The significantly enhanced efficiency can be attributed to the
      combination of the desirable electron transport property obtained by the
      intentionally introduced SnO2 nanosheets (NSs) and the effectively retained
      inherent characteristics of SnO2 NAs, i.e., large surface area and strong light
      scattering effect. This work provides a promising approach for the rapid
      development of highly efficient SnO2 photoanode film-based DSCs with the
      properties of simplicity of operation and control over the photoanode
      composition.

PMID- 30235799
TI  - Atmospheric-Pressure Cold Plasma Activating Au/P25 for CO Oxidation: Effect of
      Working Gas.
AB  - Commercial TiO2 (P25) supported gold (Au/P25) attracts increasing attention. In
      this work, atmospheric-pressure (AP) cold plasma was employed to activate the
      Au/P25-As catalyst prepared by a modified impregnation method. The influence of
      cold plasma working gas (oxygen, argon, hydrogen, and air) on the structure and
      performance of the obtained Au/P25 catalysts was investigated. X-ray diffraction
      (XRD), UV-Vis diffuse reflectance spectroscopy (DRS), transmission electron
      microscopy (TEM), and X-ray spectroscopy (XPS) were adopted to characterize the
      Au/P25 catalysts. CO oxidation was used as model reaction probe to test the
      Au/P25 catalyst. XRD results reveal that supporting gold and AP cold plasma
      activation have little effect on the P25 support. CO oxidation activity over the
      Au/P25 catalysts follows the order: Au/P25-O2P > Au/P25-As > Au/P25-ArP ~ Au/P25
      H2P > Au/P25-AirP. Au/P25-AirP presents the poorest CO oxidation catalytic
      activity among the Au/P25 catalysts, which may be ascribed to the larger size of
      gold nanoparticles, low concentration of active [O]s, as well as the poisoning
      [NOx]s. The poor catalytic performance of Au/P25-ArP and Au/P25-H2P is ascribed
      to the lower concentration of [O]s species. 100% CO conversion temperatures for
      Au/P25-O2P is 40  degrees C, which is 30  degrees C lower than that over the as
      prepared Au/P25-As catalyst. The excellent CO oxidation activity over Au/P25-O2P
      is mainly attributed to the efficient decomposition of gold precursor species,
      small size of gold nanoparticles, and the high concentration of [O]s species.

PMID- 30235800
TI  - The Use of Galleria mellonella Larvae to Identify Novel Antimicrobial Agents
      against Fungal Species of Medical Interest.
AB  - The immune system of insects and the innate immune response of mammals share many
      similarities and, as a result, insects may be used to assess the virulence of
      fungal pathogens and give results similar to those from mammals. Larvae of the
      greater wax moth Galleria mellonella are widely used in this capacity and also
      for assessing the toxicity and in vivo efficacy of antifungal drugs. G.
      mellonella larvae are easy to use, inexpensive to purchase and house, and have
      none of the legal/ethical restrictions that are associated with use of mammals.
      Larvae may be inoculated by intra-hemocoel injection or by force-feeding. Larvae
      can be used to assess the in vivo toxicity of antifungal drugs using a variety of
      cellular, proteomic, and molecular techniques. Larvae have also been used to
      identify the optimum combinations of antifungal drugs for use in the treatment of
      recalcitrant fungal infections in mammals. The introduction of foreign material
      into the hemocoel of larvae can induce an immune priming effect which may operate
      independently with the activity of the antifungal drug. Procedures to identify
      this effect and limit its action are required.

PMID- 30235801
TI  - Accelerated Curing and Enhanced Material Properties of Conductive Polymer
      Nanocomposites by Joule Heating.
AB  - Joule heating is useful for fast and reliable manufacturing of conductive
      composite materials. In this study, we investigated the influence of Joule
      heating on curing conditions and material properties of polymer-based conductive
      composite materials consisting of carbon nanotubes (CNTs) and
      polydimethylsiloxane (PDMS). We applied different voltages to the CNT
      nanocomposites to investigate their electrical stabilization, curing temperature,
      and curing time. The result showed that highly conductive CNT/PDMS composites
      were successfully cured by Joule heating with uniform and fast heat distribution.
      For a 7.0 wt % CNT/PDMS composite, a high curing temperature of around 100 
      degrees C was achieved at 20 V with rapid temperature increase. The conductive
      nanocomposite cured by Joule heating also revealed an enhancement in mechanical
      properties without changing the electrical conductivities. Therefore, CNT/PDMS
      composites cured by Joule heating are useful for expediting the manufacturing
      process for particulate conductive composites in the field of flexible and large
      area sensors and electronics, where fast and uniform curing is critical to their
      performance.

PMID- 30235802
TI  - Ca2+ Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve
      the Cation Channel TRPV2.
AB  - Peritubular cells are part of the wall of seminiferous tubules in the human
      testis and their contractile abilities are important for sperm transport. In
      addition, they have immunological roles. A proteomic analysis of isolated human
      testicular peritubular cells (HTPCs) revealed expression of the transient
      receptor potential channel subfamily V member 2 (TRPV2). This cation channel is
      linked to mechano-sensation and to immunological processes and inflammation in
      other organs. We verified expression of TRPV2 in peritubular cells in human
      sections by immunohistochemistry. It was also found in other testicular cells,
      including Sertoli cells and interstitial cells. In cultured HTPCs, application of
      cannabidiol (CBD), a known TRPV2 agonist, acutely induced a transient increase in
      intracellular Ca2+ levels. These Ca2+ transients could be blocked both by
      ruthenium red, an unspecific Ca2+ channel blocker, and tranilast (TRA), an
      antagonist of TRPV2, and were also abolished when extracellular Ca2+ was removed.
      Taken together this indicates functional TRPV2 channels in peritubular cells.
      When applied for 24 to 48 h, CBD induced expression of proinflammatory factors.
      In particular, mRNA and secreted protein levels of the proinflammatory chemokine
      interleukin-8 (IL-8/CXCL8) were elevated. Via its known roles as a major mediator
      of the inflammatory response and as an angiogenic factor, this chemokine may play
      a role in testicular physiology and pathology.

PMID- 30235803
TI  - Robust Step Counting for Inertial Navigation with Mobile Phones.
AB  - Mobile phones are increasingly used for purposes that have nothing to do with
      phone calls or simple data transfers, and one such use is indoor inertial
      navigation. Nevertheless, the development of a standalone application able to
      detect the displacement of the user starting only from the data provided by the
      most common inertial sensors in the mobile phones (accelerometer, gyroscope and
      magnetometer), is a complex task. This complexity lies in the hardware disparity,
      noise on data, and mostly the many movements that the mobile phone can experience
      and which have nothing to do with the physical displacement of the owner. In our
      case, we describe a proposal, which, after using quaternions and a Kalman filter
      to project the sensors readings into an Earth Centered inertial reference system,
      combines a classic Peak-valley detector with an ensemble of SVMs (Support Vector
      Machines) and a standard deviation based classifier. Our proposal is able to
      identify and filter out those segments of signal that do not correspond to the
      behavior of "walking", and thus achieve a robust detection of the physical
      displacement and counting of steps. We have performed an extensive experimental
      validation of our proposal using a dataset with 140 records obtained from 75
      different people who were not connected to this research.

PMID- 30235805
TI  - Building-Related Environmental Intolerance and Associated Health in the General
      Population.
AB  - People frequently attribute adverse symptoms to particular buildings when
      exposure to pollutants is low, within nonhazardous levels. Our aim was to
      characterize building-related intolerance (BRI) in the general population. Data
      were derived from two population-based questionnaire surveys, the Vasterbotten
      and Osterbotten Environmental Health Study. We identified cases of BRI if
      respondents reported symptoms emerging from residing in certain buildings, when
      most other people had none. The questionnaires covered lifestyle factors,
      perceived general health, BRI duration and symptom frequency, the emotional and
      behavioral impact of BRI, coping strategies, and physician-diagnosed diseases.
      From the total of 4941 participants, we formed two case groups, 275 (5.6%)
      fulfilled criteria for self-reported BRI, and 123 (2.5%) for BRI with wide
      ranging symptoms. Individuals in both case groups were significantly more often
      female, single, and perceived their general health as poorer than the referents,
      i.e., those reporting no BRI symptoms. The mean duration of BRI was 12 years. In
      both case groups, avoidance behavior was found in over 60%, and nearly half of
      the sample had sought medical care. BRI with wide-ranging symptoms was associated
      with elevated odds for all studied comorbidities (somatic and psychiatric
      diseases and functional somatic syndromes). The perceived health of individuals
      with BRI is poorer and comorbidities are more frequent than among referents. BRI
      seems to be similar to other environmental intolerances and shares features with
      functional somatic syndromes.

PMID- 30235808
TI  - Partnerships between an At-Risk Youth CrossFit Program and Local Community
      Organizations: Focusing on the Antecedents to Partnership Development.
AB  - A large body of research has established that sport intervention programs can
      have social, emotional and health benefits for at-risk youth. While research has
      focused on the positive outcomes associated with these programs, little attention
      has been given to program inputs. It is recognized that community partnerships
      can help intervention programs achieve their goals. Yet, how are such
      partnerships formed and what can help to promote the successful formation of
      partnerships? This paper provides a detailed account of the partnership
      implementation process undertaken to develop and deliver a health promotion
      physical activity program for at-risk youth through the medium of CrossFit in a
      low socioeconomic area in a rural community in the southeastern United States.
      Developing successful partnerships serves as a valuable component to help
      organizations obtain resources and skills needed to initiate and continue
      programs for underserved populations. The scholars identify and explain how
      critical success factors such as personal contact, partnership complementarity
      and fit and the promotion of high levels of commitment and trust, serve as
      important starting points for developing and maintaining strong community
      partnerships.

PMID- 30235807
TI  - Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD.
AB  - The two main subsets of nonalcoholic fatty liver disease (NAFLD) include: (1)
      nonalcoholic fatty liver (NAFL), the more common and non-progressive subtype; and
      (2) nonalcoholic steatohepatitis (NASH), the less common subtype, which has the
      potential to progress to advanced liver damage. Current treatment strategies have
      focused on lifestyle management of modifiable risk factors, namely weight, and on
      the optimization of the management of individual components of metabolic
      syndrome. Various hypothetical pathogenic mechanisms have been proposed, leading
      to the development of novel drugs with the potential to effectively treat
      patients with NASH. Numerous clinical trials are ongoing, utilizing these
      experimental drugs and molecules targeting specific mechanistic pathway(s) to
      effectively treat NASH. Some of these mechanistic pathways targeted by
      experimental pharmacologic agents include chemokine receptor 2 and 5 antagonism,
      inhibition of galectin-3 protein, antagonism of toll-like receptor 4, variation
      of fibroblast growth factor 19, agonism of selective thyroid hormone receptor
      beta, inhibition of apoptosis signal-regulating kinase 1, inhibition of acetyl
      coenzyme A carboxylase, agonism of farnesoid X receptor, antibodies against lysl
      oxidase-like-2, and inhibition of inflammasomes. Emerging data are promising and
      further updates from ongoing clinical trials are eagerly awaited.

PMID- 30235806
TI  - A Semimetal-Like Molybdenum Carbide Quantum Dots Photoacoustic Imaging and
      Photothermal Agent with High Photothermal Conversion Efficiency.
AB  - Theranostic platforms integrating imaging diagnostic and therapeutic
      interventions into a single nanoplatform have attracted considerable attention
      for cancer-individualized therapies. However, their uncertain stability, complex
      pharmacokinetics, and intrinsic toxicology of multiple components hinder their
      practical application in clinical research. In this paper, stable and high
      concentration molybdenum carbide quantum dots (Mo2C QDs) with a diameter of
      approximately 6 nm and a topographic height of about 1.5 nm were synthesized
      using a facile sonication-assisted liquid-phase exfoliation approach. The
      prepared Mo2C QDs exhibited a strong near-infrared (NIR) absorbance with a high
      molar extinction coefficient of 4.424 Lg-1cm-1 at 808 nm, a high photothermal
      conversion efficiency of 42.9%, and showed excellent performance on photoacoustic
      imaging. The Mo2C QDs had high stability and highly biocompatibility, with low
      cytotoxicity. Under NIR irradiation, a remarkable in vitro and in vivo
      therapeutic effect was obtained. Such a stable and biocompatible all-in-one
      theranostic nanoagent generated by facile synthesis that combines promising
      imaging guidance and effective tumor ablation properties may hold great potential
      for theranostic nanomedicine.

PMID- 30235810
TI  - Effect of Al Element on the Microstructure and Properties of Cu-Ni-Fe-Mn Alloys.
AB  - The effects of aluminum on the mechanical properties and corrosion behavior in
      artificial seawater of Cu-Ni-Fe-Mn alloys were investigated. Cu-7Ni-xAl-1Fe-1Mn
      samples, consisting of 0, 1, 3, 5, and 7 wt % aluminum along with the same
      contents of other alloying elements (Ni, Fe, and Mn), were prepared. The
      microstructure of Cu-7Ni-xAl-1Fe-1Mn alloy was analyzed by Transmission Electron
      Microscopy (TEM), and its corrosion property was tested by an electrochemical
      system. The results show that the mechanical and corrosion properties of Cu-7Ni
      xAl-1Fe-1Mn alloy have an obvious change with the aluminum content. The tensile
      strength has a peak value of 395 MPa by adding 3 wt % aluminum in the alloy.
      Moreover, the corrosion rate in artificial seawater of Cu-7Ni-3Al-1Fe-1Mn alloy
      is 0.0215 mm/a which exhibits a better corrosion resistance than the commercially
      used UNS C70600. It is confirmed that the second-phase transformation of Cu-7Ni
      xAl-1Fe-1Mn alloy follows the sequence of alpha solid solution -> Ni3Al -> Ni3Al
      + NiAl -> Ni3Al + NiAl3. The electrochemical impedance spectroscopy (EIS) shows
      that the adding element aluminum in the Cupronickel can improve the corrosion
      resistance of Cu-7Ni-xAl-1Fe-1Mn alloy.

PMID- 30235809
TI  - Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic
      Application.
AB  - Ocular drug delivery has been a major challenge for clinical pharmacologists and
      biomaterial scientists due to intricate and unique anatomical and physiological
      barriers in the eye. The critical requirement varies from anterior and posterior
      ocular segments from a drug delivery perspective. Recently, many new drugs with
      special formulations have been introduced for targeted delivery with modified
      methods and routes of drug administration to improve drug delivery efficacy.
      Current developments in nanoformulations of drug carrier systems have become a
      promising attribute to enhance drug retention/permeation and prolong drug release
      in ocular tissue. Biodegradable polymers have been explored as the base polymers
      to prepare nanocarriers for encasing existing drugs to enhance the therapeutic
      effect with better tissue adherence, prolonged drug action, improved
      bioavailability, decreased toxicity, and targeted delivery in eye. In this
      review, we summarized recent studies on sustained ocular drug/gene delivery and
      emphasized on the nanocarriers made by biodegradable polymers such as liposome,
      poly lactic-co-glycolic acid (PLGA), chitosan, and gelatin. Moreover, we
      discussed the bio-distribution of these nanocarriers in the ocular tissue and
      their therapeutic applications in various ocular diseases.

PMID- 30235811
TI  - Determination of Total Polysaccharides and Total Flavonoids in Chrysanthemum
      morifolium Using Near-Infrared Hyperspectral Imaging and Multivariate Analysis.
AB  - The rapid and nondestructive determination of active compositions in
      Chrysanthemum morifolium (Hangbaiju) is of great value for producers and
      consumers. Hyperspectral imaging as a rapid and nondestructive technique was used
      to determine total polysaccharides and total flavonoids content in Chrysanthemum
      morifolium. Hyperspectral images of different sizes of Chrysanthemum morifolium
      flowers were acquired. Pixel-wise spectra within all samples were preprocessed by
      wavelet transform (WT) followed by standard normal variate (SNV). Partial least
      squares (PLS) and least squares-support vector machine (LS-SVM) were used to
      build prediction models using sample average spectra calculated by preprocessed
      pixel-wise spectra. The LS-SVM model performed better than the PLS models, with
      the determination of the coefficient of calibration (R2c) and prediction (R2p)
      being over 0.90 and the residual predictive deviation (RPD) being over 3 for
      total polysaccharides and total flavonoids content prediction. Prediction maps of
      total polysaccharides and total flavonoids content in Chrysanthemum morifolium
      flowers were successfully obtained by LS-SVM models, which exhibited the best
      performances. The overall results showed that hyperspectral imaging was a
      promising technique for the rapid and accurate determination of active
      ingredients in Chrysanthemum morifolium, indicating the great potential to
      develop an online system for the quality determination of Chrysanthemum
      morifolium.

PMID- 30235812
TI  - The Effects of Exercise Induced Muscle Damage on Knee Joint Torque and Balance
      Performance.
AB  - The purpose of this investigation is to determine the effects of exercise induced
      muscle damage (EIMD) on balance and knee joint torque. Thirteen males and females
      volunteered to participate in the study. Following a familiarization session,
      baseline measures were obtained for isometric torque measured during a maximal
      voluntary isometric contraction (MVIC) for knee flexors and extensors, and ankle
      dorsi-flexors and plantar-flexors. Additionally, balance performance was tested
      in double leg (DL), and right single leg (RSL) static and dynamic unstable
      stability was measured. Participants then performed the muscle damage protocol of
      front loaded Bulgarian split squats. All measurements were re-assessed for torque
      and balance immediately and up to 72 h afterwards. A one-way repeated-measures
      analysis of variance (ANOVA) was used to analyze differences between baseline and
      all time-points for torque and balance measures. There was a significant time
      effect for knee extensors MVIC torque, where baseline measures are greater than
      post EIMD, 24 h and 48 h post EIMD. There was no significant time effect for all
      balance conditions. These results provide evidence of EIMD following high
      intensity eccentric exercises with significant reductions in knee extensor torque
      up to at least 48 h and show that balance was not compromised following EIMD.

PMID- 30235813
TI  - MePHD1 as a PHD-Finger Protein Negatively Regulates ADP-Glucose Pyrophosphorylase
      Small Subunit1a Gene in Cassava.
AB  - ADP-glucose pyrophosphorylase (AGPase) is an important enzyme in the starch
      synthesis pathway. Its enzyme activity can determine the efficiency of starch
      biosynthesis. Cassava (Manihot esculenta Crantz) is the main staple crop
      worldwide and has a high starch content in its storage root. However, the inner
      regulatory mechanism of AGPase gene family is unclear. MePHD1; a plant
      homeodomain transcription factor; was isolated through a yeast one-hybrid
      screening using the promoter of ADP-glucose pyrophosphorylase small subunit1a
      (MeAGPS1a) as bait, and cassava storage root cDNA library as prey. This factor
      could bind to the MeAGPS1a promoter in vitro and in vivo, and its predicted
      binding region ranged from -400 bp to -201 bp, at the translation initiation
      site. The transcript level of MePHD1 could be induced by five plant hormones, and
      a temperature of 42  degrees C. This was down-regulated during the maturation
      process of the storage root. MePHD1 protein could repress the promoter activity
      of MeAGPS1a gene by a dual-luciferase assay; which indicated that MePHD1 is a
      negative regulator for the transcript level of MeAGPS1a gene.

PMID- 30235814
TI  - Establishing Heat Alert Thresholds for the Varied Climatic Regions of British
      Columbia, Canada.
AB  - Following an extreme heat event in 2009, a Heat Alert and Response System (HARS)
      was implemented for the greater Vancouver area of British Columbia (BC), Canada.
      This system has provided a framework for guiding public health interventions and
      assessing population response and adaptation to extreme heat in greater
      Vancouver, but no other parts of BC were covered by HARS. The objective of this
      study was to identify evidence-based heat alert thresholds for the Southwest,
      Southeast, Northwest, and Northeast regions to facilitate the introduction of
      HARS across BC. This was done based on a national approach that considers high
      temperatures on two consecutive days and the intervening overnight low, referred
      to as the high-low-high approach. Daily forecast and observed air temperatures
      and daily mortality counts for May through September of 2004 through 2016 were
      obtained. For each date (dayt), dayt-2 forecasts were used to assign high
      temperatures for dayt and dayt+1 and the overnight low. A range of high-low-high
      threshold combinations was assessed for each region by finding associations with
      daily mortality using time-series models and other considerations. The following
      thresholds were established: 29-16-29  degrees C in the Southwest; 35-18-35 
      degrees C in the Southeast; 28-13-28  degrees C in the Northwest; and 29-14-29 
      degrees C in the Northeast. Heat alert thresholds for all regions in BC provide
      health authorities with information on dangerously hot temperature conditions and
      inform the activation of protective public health interventions.

PMID- 30235804
TI  - Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and
      Evolution towards Precision Medicine.
AB  - Duchenne's muscular dystrophy is an X-linked neuromuscular disease that manifests
      as muscle atrophy and cardiomyopathy in young boys. However, a considerable
      percentage of carrier females are often diagnosed with cardiomyopathy at an
      advanced stage. Existing therapy is not disease-specific and has limited effect,
      thus many patients and symptomatic carrier females prematurely die due to heart
      failure. Early detection is one of the major challenges that muscular dystrophy
      patients, carrier females, family members and, research and medical teams face in
      the complex course of dystrophic cardiomyopathy management. Despite the
      widespread adoption of advanced imaging modalities such as cardiac magnetic
      resonance, there is much scope for refining the diagnosis and treatment of
      dystrophic cardiomyopathy. This comprehensive review will focus on the pertinent
      clinical aspects of cardiac disease in muscular dystrophy while also providing a
      detailed consideration of the known and developing concepts in the
      pathophysiology of muscular dystrophy and forthcoming therapeutic options.

PMID- 30235815
TI  - Changes in Work Practices for Safe Use of Formaldehyde in a University-Based
      Anatomy Teaching and Research Facility.
AB  - Anatomy teaching and research relies on the use of formaldehyde (FA) as a
      preservation agent for human and animal tissues. Due to the recent classification
      of FA as a carcinogen, university hospitals are facing a challenge to (further)
      reduce exposure to FA. The aim of this study was to reduce exposure to FA in the
      anatomy teaching and research facility. Workers participated in the development
      of improved work practices, both technical and organizational solutions. Over a
      period of 6 years mitigating measures were introduced, including improvement of a
      down-flow ventilation system, introduction of local exhaust ventilation,
      collection of drain liquid from displayed specimens in closed containers and leak
      prevention. Furthermore, some organizational changes were made to reduce the
      number of FA peak exposures. Stationary and personal air sampling was performed
      in three different campaigns to assess the effect of these new work practices on
      inhalation exposure to FA. Samples were collected over 8 h (full shift) and 15
      min (task-based) to support mitigation of exposure and improvement of work
      practices. Air was collected on an adsorbent coated with 2,4
      dinitrophenylhydrazine (DNPH) and analyzed by HPLC-UV. Geometric mean (GM)
      concentrations of FA in the breathing zone over a work-shift were 123 ug/m3 in
      2012 and 114 ug/m3 in 2014, exceeding the workplace standard of 150 ug/m3 (8 h
      time-weighted average, TWA) on 46% of the workdays in 2012 and 38% of the
      workdays in 2014. This exposure was reduced to an average of 28.8 ug/m3 in 2017
      with an estimated probability of exceeding the OEL of 0.6%. Task-based
      measurements resulted in a mean peak exposures of 291 ug/m3 in 2012 (n = 19) and
      a mean of 272 ug/m3 in 2014 (n = 21), occasionally exceeding the standard of 500
      ug/m3 (15 min TWA), and were reduced to a mean of 88.7 ug/m3 in 2017 (n = 12)
      with an estimated probability of exceeding the OEL of 1.6%.

PMID- 30235816
TI  - Successful Aging and Chronic Osteoarthritis.
AB  - Background: Aging is commonly accepted as a time period of declining heath in
      most cases. This review aimed to examine the research base concerning the use of
      the term 'successful aging', a process and outcome deemed desirable, but
      challenging to attain. A second was to provide related information to demonstrate
      how health professionals as well as individuals can aim for a 'successful aging'
      process and outcome, despite the presence of disabling osteoarthritis. Methods:
      Information specifically focusing on 'successful aging' and the concept of
      improving opportunities for advancing 'successful aging' despite osteoarthritis
      was sought. Results: Among the many articles on 'successful aging', several
      authors highlight the need to include, a broader array of older adults into the
      conceptual framework. Moreover, conditions such as osteoarthritis should not
      necessarily preclude the individual from attaining a personally valued successful
      aging outcome. Conclusions: Pursuing more inclusive research and research
      designs, and not neglecting to include people with chronic osteoarthritis can
      potentially heighten the life quality of all aging individuals, while reducing
      pain and depression, among other adverse aging and disability correlates among
      those with osteoarthritis.

PMID- 30235817
TI  - Shadow Puppets and Neglected Diseases: Evaluating a Health Promotion Performance
      in Rural Indonesia.
AB  - 'Rama and the Worm' is a shadow puppet production targeting neglected diseases in
      Central Java. It is an entertainment-based intervention study to promote health
      by reducing the impact of parasitic diseases such as soil-transmitted helminths
      (STH). The study uses traditional Javanese shadow puppetry (wayang kulit) as a
      vehicle in village communities to disseminate health messages and promote
      behaviour change to prevent diseases caused, primarily, by inadequate sanitation
      and poor hygiene. The health education messages contained in the play, although
      using traditional characters and themes, required the creation of a completely
      new narrative script, using characters and plot lines familiar to the wayang
      kulit repertoire, but placing them in new situations that relate specifically to
      health promotion objectives. The intervention was piloted in a village in Central
      Java, Indonesia using a pre/post design with both qualitative and quantitative
      analysis. A total of 96 male and female villagers, aged between 7 and 87 years,
      provided both baseline and follow up data. Participant knowledge and behaviours
      related to gastrointestinal and helminth-related disease were assessed before and
      after the intervention through a questionnaire administered by interview. Results
      revealed statistically significant improvements in both knowledge (48.6% pre
      intervention score vs. 62.8% post-intervention score, p < 0.001) and behaviour
      (77.4% vs. 80.6%, p = 0.004) related to gastrointestinal and helminth disease.
      Findings of the study indicate the wayang kulit performance is an effective
      health education tool. The results provide proof of concept with scaling up the
      next step forward. The wayang kulit production provides a significant additional
      component for an integrated, comprehensive approach to reduction and elimination
      of STH infection.

PMID- 30235818
TI  - Zingerone Suppresses Tumor Development through Decreasing Cyclin D1 Expression
      and Inducing Mitotic Arrest.
AB  - Cancer cells undergo uncontrolled proliferation resulting from aberrant activity
      of various cell-cycle proteins. Therefore, despite recent advances in intensive
      chemotherapy, it is difficult to cure cancer completely. Recently, cell-cycle
      regulators became attractive targets in cancer therapy. Zingerone, a phenolic
      compound isolated from ginger, is a nontoxic and inexpensive compound with varied
      pharmacological activities. In this study, the therapeutic effect of zingerone as
      an anti-mitotic agent in human neuroblastoma cells was investigated. Following
      treatment of BE(2)-M17 cells with zingerone, we performed a 3-(4,5
      dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and colony
      formation assay to evaluate cellular proliferation, in addition to
      immunofluorescence cytochemistry and flow cytometry to examine the mitotic cells.
      The association of gene expression with tumor stage and survival was analyzed.
      Furthermore, to examine the anti-cancer effect of zingerone, we applied a BALB/c
      mouse-tumor model using a BALB/c-derived adenocarcinoma cell line. In human
      neuroblastoma cells, zingerone inhibited cellular viability and survival.
      Moreover, the number of mitotic cells, particularly those in prometaphase,
      increased in zingerone-treated neuroblastoma cells. Regarding specific molecular
      mechanisms, zingerone decreased cyclin D1 expression and induced the cleavage of
      caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1). The decrease in cyclin D1
      and increase in histone H3 phosphorylated (p)-Ser10 were confirmed by
      immunohistochemistry in tumor tissues administered with zingerone. These results
      suggest that zingerone induces mitotic arrest followed by inhibition of growth of
      neuroblastoma cells. Collectively, zingerone may be a potential therapeutic drug
      for human cancers, including neuroblastoma.

PMID- 30235819
TI  - Piezoelectric Effect and Electroactive Phase Nucleation in Self-Standing Films of
      Unpoled PVDF Nanocomposite Films.
AB  - Novel polymer-based piezoelectric nanocomposites with enhanced electromechanical
      properties open new opportunities for the development of wearable energy
      harvesters and sensors. This paper investigates how the dissolution of different
      types of hexahydrate metal salts affects beta-phase content and piezoelectric
      response (d33) at nano- and macroscales of polyvinylidene fluoride (PVDF)
      nanocomposite films. The strongest enhancement of the piezoresponse is observed
      in PVDF nanocomposites processed with Mg(NO3)2?6H2O. The increased piezoresponse
      is attributed to the synergistic effect of the dipole moment associated with the
      nucleation of the electroactive phase and with the electrostatic interaction
      between the CF2 group of PVDF and the dissolved salt through hydrogen bonding.
      The combination of nanofillers like graphene nanoplatelets or zinc oxide nanorods
      with the hexahydrate salt dissolution in PVDF results in a dramatic reduction of
      d33, because the nanofiller assumes a competitive role with respect to H-bond
      formation between PVDF and the dissolved metal salt. The measured peak value of
      d33 reaches the local value of 13.49 pm/V, with an average of 8.88 pm/V over an
      area of 1 cm2. The proposed selection of metal salt enables low-cost production
      of piezoelectric PVDF nanocomposite films, without electrical poling or
      mechanical stretching, offering new opportunities for the development of devices
      for energy harvesting and wearable sensors.

PMID- 30235820
TI  - Cloning of the Bisucaberin B Biosynthetic Gene Cluster from the Marine Bacterium
      Tenacibaculum mesophilum, and Heterologous Production of Bisucaberin B.
AB  - The biosynthetic gene cluster for bisucaberin B (1, bsb gene cluster), an N
      hydroxy-N-succinyl diamine (HSD)-based siderophore, was cloned from the marine
      bacterium Tenacibaculum mesophilum, originated from a marine sponge. The bsb gene
      cluster consists of six open reading frames (ORFs), in contrast to the four ORFs
      typically seen in biosynthetic gene clusters of the related molecules.
      Heterologous expression of the key enzyme, BsbD2, which is responsible for the
      final biosynthetic step of 1 resulted in production of bisucaberin B (1), but not
      bisucaberin (2) a macrocyclic counterpart of 1. To date, numbers of related
      enzymes producing macrocyclic analogues have been reported, but this work
      represents the first example of the HSD-based siderophore biosynthetic enzyme
      which exclusively produces a linear molecule rather than macrocyclic
      counterparts.

PMID- 30235821
TI  - alpha-Tocopheryl Succinate-Based Polymeric Nanoparticles for the Treatment of
      Head and Neck Squamous Cell Carcinoma.
AB  - The aim of this work is to study, in an in vitro head and neck squamous cell
      carcinomas model the anti-angiogenic and anti-migratory properties of self
      assembled polymeric nanoparticles (NPs) with demonstrated selective anticancer
      activity. The NPs are based on alpha-tocopheryl succinate (alpha-TOS)
      encapsulated in the hydrophobic core of the NPs. We analyzed the effect of the
      newly synthetized alpha-TOS-loaded NPs in proliferating endothelial cells and
      hypopharynx carcinoma squamous cells and measured markers of angiogenesis,
      apoptosis and reactive oxygen species (ROS). alpha-TOS-loaded NPs suppressed
      angiogenesis by inducing accumulation of ROS and inducing apoptosis of
      proliferating endothelial cells. These NPs also decrease the number and quality
      of capillary-like tubes in an in vitro three-dimensional (3D) experiment,
      decrease the production of the pro-angiogenic vascular endothelial growth factor
      and down-regulate the expression of its receptor. The anti-migratory efficacy of
      alpha-TOS is corroborated in hypopharynx carcinoma cells by decreasing the
      secretion of matrix metalloproteases 2 and 9 (MMP-2 and MMP-9) and inhibiting
      cell migration. These results confirm that alpha-TOS-based NPs not only present
      anticancer properties, but also antiangiogenic properties, therefore making them
      promising candidates for multi-active combinatorial anticancer therapy.

PMID- 30235823
TI  - Altered Glucosinolate Profiles and Expression of Glucosinolate Biosynthesis Genes
      in Ringspot-Resistant and Susceptible Cabbage Lines.
AB  - Ringspot, caused by the fungus Mycosphaerella brassicicola, is a serious disease
      of Brassica crops worldwide. Despite noteworthy progress to reveal the role of
      glucosinolates in pathogen defense, the host-pathogen interaction between cabbage
      (Brassica oleracea) and M. brassicicola has not been fully explored. Here, we
      investigated the glucosinolate profiles and expression of glucosinolate
      biosynthesis genes in the ringspot-resistant (R) and susceptible (S) lines of
      cabbage after infection with M. brassicicola. The concomitant rise of aliphatic
      glucoiberverin (GIV) and indolic glucobrassicin (GBS) and methoxyglucobrassicin
      (MGBS) was linked with ringspot resistance in cabbage. Pearson's correlation and
      principle component analysis showed a significant positive association between
      GIV contents and the expression of the glucosinolate biosynthesis gene ST5b
      Bol026202 and between GBS contents and the expression of the glucosinolate
      biosynthesis gene MYB34-Bol017062. Our results confirmed that M. brassicicola
      infection induces the expression of glucosinolate biosynthesis genes in cabbage,
      which alters the content of individual glucosinolates. This link between the
      expression of glucosinolate biosynthesis genes and the accumulation of their
      respective glucosinolates with the resistance to ringspot extends our molecular
      sense of glucosinolate-negotiated defense against M. brassicicola in cabbage.

PMID- 30235822
TI  - Iron in Friedreich Ataxia: A Central Role in the Pathophysiology or an
      Epiphenomenon?
AB  - Friedreich ataxia is a neurodegenerative disease with an autosomal recessive
      inheritance. In most patients, the disease is caused by the presence of
      trinucleotide GAA expansions in the first intron of the frataxin gene. These
      expansions cause the decreased expression of this mitochondrial protein. Many
      evidences indicate that frataxin deficiency causes the deregulation of cellular
      iron homeostasis. In this review, we will discuss several hypotheses proposed for
      frataxin function, their caveats, and how they could provide an explanation for
      the deregulation of iron homeostasis found in frataxin-deficient cells. We will
      also focus on the potential mechanisms causing cellular dysfunction in Friedreich
      Ataxia and on the potential use of the iron chelator deferiprone as a therapeutic
      agent for this disease.

PMID- 30235824
TI  - Feature Extraction from Indirect Monitoring in Marine Oil Separation Systems.
AB  - In this article, a study of characteristic vibrations of marine oils separation
      system is presented. Vibrations analysis allows for the extraction of
      representative features that could be related to the lifetime of their pieces.
      Actual measurements were carried out on these systems on Ro-Pax vessels to
      transport passengers and freight. The vibrations obtained were processed in the
      frequency domain and following this, they were used in a Genetic Neuro-Fuzzy
      System in order to design new predictive maintenance strategies. The obtained
      results show that these techniques as a promising strategy can be utilized to
      determine incipient faults.

PMID- 30235825
TI  - Platycodon grandiflorum Saponins Ameliorate Cisplatin-Induced Acute
      Nephrotoxicity through the NF-kappaB-Mediated Inflammation and PI3K/Akt/Apoptosis
      Signaling Pathways.
AB  - Although cisplatin is a potent chemotherapeutic agent against cancers, its
      clinical application is seriously limited by its severe side effects of
      nephrotoxicity. Previous studies reported that saponins isolated from the roots
      of Platycodon grandiflorum (PGS) exerted protective effects in various animal
      models of renal injury, with no confirmation on cisplatin-induced injury. This
      study was designed to investigate the protective effect of PGS (15 and 30 mg/kg)
      on cisplatin-induced kidney injury in mice. The levels of serum creatinine (CRE)
      and blood urea nitrogen (BUN), and renal histopathology demonstrated the
      protective effect of PGS against cisplatin-induced kidney injury. PGS exerted
      anti-inflammation effects via suppressing nuclear factor-kappa B (NF-kappaB)
      activation and alleviating the cisplatin-induced increase in inducible nitric
      oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF
      alpha), and interleukin-1beta (IL-1beta) in kidney tissues. The expressions of
      phosphorylation of phosphatidylinositol 3-kinase/protein kinase B and its
      downstream apoptotic factors, such as Bcl-2 and caspase families were regulated
      by PGS in a dose-dependent manner. In conclusion, PGS exerted kidney protection
      effects against cisplatin-induced kidney injury by inhibiting the activation of
      NF-kappaB and regulating PI3K/Akt/apoptosis signaling pathways in mice.

PMID- 30235826
TI  - A Disposable and Multi-Chamber Film-Based PCR Chip for Detection of Foodborne
      Pathogen.
AB  - Since the increment of the threat to public health caused by foodborne pathogens,
      researches have been widely studied on developing the miniaturized detection
      system for the on-site pathogen detection. In the study, we focused on the
      development of portable, robust, and disposable film-based polymerase chain
      reaction (PCR) chip containing a multiplex chamber for simultaneous gene
      amplification. In order to simply fabricate and operate a film-based PCR chip,
      different kinds of PCR chambers were designed and fabricated using polyethylene
      terephthalate (PET) and polyvinyl chloride (PVC) adhesive film, in comparison
      with commercial PCR, which employs a stereotyped system at a bench-top scale. No
      reagent leakage was confirmed during the PCR thermal cycling using the film PCR
      chip, which indicates that the film PCR chip is structurally stable for rapid
      heat cycling for DNA amplification. Owing to use of the thin film to fabricate
      the PCR chip, we are able to realize fast thermal transfer from the heat block
      that leads to short PCR amplification time. Moreover, using the film PCR chip, we
      could even amplify the target pathogen with 10 CFU mL-1. The artificially
      infected milk with various concentration of Bacillus cereus was successfully
      amplified on a single film PCR chip. On the basis of the reliable results, the
      developed film PCR chip could be a useful tool as a POCT device to detect
      foodborne pathogens via genetic analysis.

PMID- 30235827
TI  - Quality Analysis of American Ginseng Cultivated in Heilongjiang Using UPLC-ESI-
      MRM-MS with Chemometric Methods.
AB  - American ginseng (Panax quinquefolium) has long been cultivated in China for the
      function food and medicine. Here, ultra-high performance liquid chromatography
      was coupled with electrospray ionization and triple quadrupole mass spectrometry
      (UPLC-ESI--TQ-MS) for simultaneous detection of 22 ginsenosides in American
      ginseng cultivated in Mudanjiang district of Heilongjiang. The extraction
      conditions also were optimized by a Box Behnken design experiment. The optimized
      result was 31.8 mL/g as ratio of liquid to raw materials, 20.3 min of extraction
      time, and 235.0 W of extraction powers. The quantitative MS parameters for these
      22 compounds were rapidly optimized by single factor experiments employing UPLC
      ESI--multiple reaction monitoring or multiple ion monitoring (MRM/MIM) scans.
      Furthermore, the established UPLC-ESI--MRM-MS method showed good linear
      relationships (R2 > 0.99), repeatability (RSD < 3.86%), precision (RSD < 2.74%),
      and recovery (94-104%). This method determined 22 bioactive ginsenosides in
      different parts of the plant (main roots, hairy roots, rhizomes, leaves, and
      stems) and growth years (one year to four years) of P. quinquefolium. The highest
      total content of the 22 analytes was in the hairy roots (1.3 * 105 ug/g) followed
      by rhizomes (7.1 * 104 ug/g), main roots (6.5 * 104 ug/g), leaves (4.2 * 104
      ug/g), and stems (2.4 * 104 ug/g). Finally, chemometric methods, hierarchical
      clustering analysis (HCA) and partial least squares discrimination analysis (PLS
      DA), were successfully used to classify and differentiate American ginseng
      attributed to different growth years. The proposed UPLC-ESI--MRM-MS coupled with
      HCA and PLS-DA methods was elucidated to be a simple and reliable method for
      quality evaluation of American ginseng.

PMID- 30235828
TI  - Non-Alcoholic Fatty Liver Disease in Overweight Children: Role of Fructose Intake
      and Dietary Pattern.
AB  - The role of nutrition and diet in the development of non-alcoholic fatty liver
      disease (NAFLD) is still not fully understood. In the present study, we
      determined if dietary pattern and markers of intestinal permeability differ
      between overweight children with and without NAFLD. In addition, in a feasibility
      study, we assessed the effect of a moderate dietary intervention only focusing on
      nutrients identified to differ between groups on markers of intestinal barrier
      function and health status. Anthropometric data, dietary intake, metabolic
      parameters, and markers of inflammation, as well as of intestinal permeability,
      were assessed in overweight children (n = 89, aged 5-9) and normal-weight healthy
      controls (n = 36, aged 5-9). Sixteen children suffered from early signs of NAFLD,
      e.g., steatosis grade 1 as determined by ultrasound. Twelve children showing
      early signs of NAFLD were enrolled in the intervention study (n = 6 intervention,
      n = 6 control). Body mass index (BMI), BMI standard deviation score (BMI-SDS),
      and waist circumference were significantly higher in NAFLD children than in
      overweight children without NAFLD. Levels of bacterial endotoxin,
      lipopolysaccharide-binding protein (LBP), and proinflammatory markers like
      interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) were also
      significantly higher in overweight children with NAFLD compared to those without.
      Total energy and carbohydrate intake were higher in NAFLD children than in those
      without. The higher carbohydrate intake mainly resulted from a higher total
      fructose and glucose intake derived from a significantly higher consumption of
      sugar-sweetened beverages. When counseling children with NAFLD regarding fructose
      intake (four times, 30-60 min within 1 year; one one-on-one counseling and three
      group counselings), neither alanine aminotransferase (ALT) nor aspartate
      aminotransferase (AST) activity in serum changed; however, diastolic blood
      pressure (p < 0.05) and bacterial endotoxin levels (p = 0.06) decreased markedly
      in the intervention group after one year. Similar changes were not found in
      uncounseled children. Our results suggest that a sugar-rich diet might contribute
      to the development of early stages of NAFLD in overweight children, and that
      moderate dietary counseling might improve the metabolic status of overweight
      children with NAFLD.

PMID- 30235829
TI  - Changes in the Elemental and Metabolite Profile of Wheat Phloem Sap during Grain
      Filling Indicate a Dynamic between Plant Maturity and Time of Day.
AB  - The long distance transport of Fe and Zn in the phloem sap of wheat (Triticum
      aestivum L.) is the key route for seed supply, due to wheat having a xylem
      discontinuity. To date, our knowledge is limited on Fe and Zn homeostasis in the
      phloem sap during the reproductive and grain filling stages. With the use of
      aphid stylectomy to collect samples of phloem sap, we explored maturity and
      morning versus afternoon (within-day) changes in nutrient and metabolite
      profiles. Phloem exudate was collected from a wheat breeding line, SAMNYT16, at
      three times during the grain filling period and at both midday and mid-afternoon.
      There were significant changes in the concentration of Mg, K, Fe and Zn during
      the course of grain loading and there were also significant within-day
      differences for Fe and K concentrations in the phloem exudate during the early
      phases of grain development. We found that, for K and Fe, there was an increase
      of 1.1- and 1.4-fold, respectively, for samples taken prior to midday to those
      from mid-afternoon. There was also a significant decrease in K, Fe and Zn phloem
      sap concentration of 1.5-, 1.4- and 1.1-fold, respectively, from the start of
      peak grain loading to the end of grain loading. Of the 79 metabolites detected
      within samples of phloem exudate, 43 had significant maturity differences and 38
      had significant within-day variability. Glutamine was found to increase by 3.3
      5.9-fold from midday to mid-afternoon and citric acid was found to decrease by
      1.6-fold from the start of grain loading to the end of grain loading. These two
      metabolites are of interest as they can complex metal ions and may play a role in
      long distance transport of metal ions. The work presented here gives further
      insight into the complex composition of the phloem sap and variability that can
      occur during the day and also with increasing maturity.

PMID- 30235831
TI  - Photocatalytic Degradation of Diclofenac by Hydroxyapatite-TiO2 Composite
      Material: Identification of Transformation Products and Assessment of Toxicity.
AB  - Diclofenac (DCF) is one of the most detected pharmaceuticals in environmental
      water matrices and is known to be recalcitrant to conventional wastewater
      treatment plants. In this study, degradation of DCF was performed in water by
      photolysis and photocatalysis using a new synthetized photocatalyst based on
      hydroxyapatite and TiO2 (HApTi). A degradation of 95% of the target compound was
      achieved in 24 h by a photocatalytic treatment employing the HApTi catalyst in
      comparison to only 60% removal by the photolytic process. The investigation of
      photo-transformation products was performed by means of UPLC-QTOF/MS/MS, and for
      14 detected compounds in samples collected during treatment with HApTi, the
      chemical structure was proposed. The determination of transformation product (TP)
      toxicity was performed by using different assays: Daphnia magna acute toxicity
      test, Toxi-ChromoTest, and Lactuca sativa and Solanum lycopersicum germination
      inhibition test. Overall, the toxicity of the samples obtained from the
      photocatalytic experiment with HApTi decreased at the end of the treatment,
      showing the potential applicability of the catalyst for the removal of diclofenac
      and the detoxification of water matrices.

PMID- 30235832
TI  - Evaluating the Accessibility of Healthcare Facilities Using an Integrated
      Catchment Area Approach.
AB  - Accessibility is a major method for evaluating the distribution of service
      facilities and identifying areas in shortage of service. Traditional
      accessibility methods, however, are largely model-based and do not consider the
      actual utilization of services, which may lead to results that are different from
      those obtained when people's actual behaviors are taken into account. Based on
      taxi GPS trajectory data, this paper proposed a novel integrated catchment area
      (ICA) that integrates actual human travel behavior to evaluate the accessibility
      to healthcare facilities in Shenzhen, China, using the enhanced two-step floating
      catchment area (E2SFCA) method. This method is called the E2SFCA-ICA method.
      First, access probability is proposed to depict the probability of visiting a
      healthcare facility. Then, integrated access probability (IAP), which integrates
      model-based access probability (MAP) and data-based access probability (DAP), is
      presented. Under the constraint of IAP, ICA is generated and divided into
      distinct subzones. Finally, the ICA and subzones are incorporated into the E2SFCA
      method to evaluate the accessibility of the top-tier hospitals in Shenzhen,
      China. The results show that the ICA not only reduces the differences between
      model-based catchment areas and data-based catchment areas, but also
      distinguishes the core catchment area, stable catchment area, uncertain catchment
      area and remote catchment area of healthcare facilities. The study also found
      that the accessibility of Shenzhen's top-tier hospitals obtained with traditional
      catchment areas tends to be overestimated and more unequally distributed in space
      when compared to the accessibility obtained with integrated catchment areas.

PMID- 30235830
TI  - Hedgehog Signaling in Lung Cancer: From Oncogenesis to Cancer Treatment
      Resistance.
AB  - Hedgehog signaling pathway is physiologically activated during embryogenesis,
      especially in lung development. It is also reactivated in many solid tumors. In
      lung cancer, Hedgehog pathway is closely associated with cancer stem cells
      (CSCs). Recent works have shown that CSCs produced a full-length Sonic Hedgehog
      (Shh) protein, with paracrine activity and induction of tumor development.
      Hedgehog pathway is also involved in tumor drug resistance in lung cancer, as
      cytotoxic chemotherapy, radiotherapy, and targeted therapies. This review
      proposes to describe the activation mechanisms of Hedgehog pathway in lung
      cancer, the clinical implications for overcoming drug resistance, and the
      perspectives for further research.

PMID- 30235833
TI  - A New Strategy for Rapidly Screening Natural Inhibitors Targeting the PCSK9/LDLR
      Interaction In Vitro.
AB  - The interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and
      the low-density lipoprotein receptor (LDLR) is a promising target for the
      treatment of hyperc-holesterolemia. In this study, a new method based on
      competitive affinity and tag detection was developed, which aimed to evaluate
      potent natural inhibitors preventing the interaction of PCSK9/LDLR directly.
      Herein, natural compounds with efficacy in the treatment of hypercholesterolemia
      were chosen to investigate their inhibitory activities on the PCSK9/LDLR
      interaction. Two of them, polydatin (1) and tetrahydroxydiphenylethylene-2-O
      glucoside (2), were identified as potential inhibitors for the PCSK9/LDLR
      interaction and were proven to prevent PCSK9-mediated LDLR degradation in HepG2
      cells. The results suggested that this strategy could be applied for evaluating
      potential bioactive compounds inhibiting the interaction of PCSK9/LDLR and this
      strategy could accelerate the discovery of new drug candidates for the treatment
      of PCSK9-mediated hypercholesterolemia.

PMID- 30235834
TI  - Spatial Assessment of Anthropogenic Impact on Trace Metal Accumulation in
      Farmland Soils from a Rapid Industrializing Region, East China.
AB  - A better understanding of anthropogenic trace metal accumulation in farmland
      soils is crucial for local food safety and public health, especially for a
      rapidly industrializing region. In this study, soil samples at two depths were
      collected from a typical county in East China and analyzed for total
      concentrations of Fe, Al, Pb, Cd, Cu, Zn, Cr, and Ni. Results showed that trace
      metals like Pb, Cd, Cu, Zn, Cr, and Ni have accumulated in the regional
      farmlands, with average topsoil concentrations 1.62-1.77 times higher than their
      background concentrations in subsoil. However, they were still much lower than
      the limits of the Chinese Environmental Quality Standard for Soils. By the proper
      calculation of enrichment factor (EF), it was found that the accumulations of
      trace metals in the topsoil have been impacted by anthropogenic activities, which
      could contribute up to 40.83% of total metal concentration. Two principal
      components were extracted according to the results of principal component
      analysis (PCA) for EF values, which indicated two important anthropogenic trace
      metal sources. With the help of spatial distribution maps based on geographical
      information system (GIS), the anthropogenic sources of Pb, Cr, and Ni were
      determined to be mostly associated with atmospheric deposition from the central
      urban area. However, Cd, Cu, and Zn were further confirmed to originate from
      different agricultural sources. The anthropogenic Cu and Zn inputs were mostly
      related to pig manure application in the rural northern and southeastern areas,
      while extensive fertilizer application was identified as the major contributor to
      anthropogenic Cd accumulation in this region. Overall, the integrated application
      of EF, PCA, and GIS mapping is an effective approach to achieve the spatial
      assessment of anthropogenic impact on trace metal accumulation in regional soils.

PMID- 30235835
TI  - Circulating Serum miRNA-205 as a Diagnostic Biomarker for Ototoxicity in Mice
      Treated with Aminoglycoside Antibiotics.
AB  - BACKGROUND: To confirm levels and detection timing of circulating microRNAs
      (miRNAs) in the serum of a mouse model for diagnosis of ototoxicity, circulating
      miR-205 in the serum was evaluated to reflect damages in the cochlear
      microstructure and compared to a kidney injury model. METHOD: A microarray for
      miRNAs in the serum was performed to assess the ototoxic effects of kanamycin
      furosemide. Changes in the levels for the selected miRNAs (miR-205, miR-183, and
      miR-103) were compared in the serum and microstructures of the cochlea (stria
      vascularis, organ of Corti, and modiolus) between the ototoxicity and normal
      mouse groups. An acute kidney injury (AKI) mouse model was used to assess changes
      in miR-205 levels in the kidney by ototoxic drugs. RESULTS: In the mouse model
      for ototoxicity, the serum levels of circulating miR-205 peaked on day 3 and were
      sustained from days 7-14. Furthermore, miR-205 expression was highly expressed in
      the organ of Corti at day 5, continued to be expressed in the modiolus at high
      levels until day 14, and was finally also in the stria vascularis. The serum miR
      205 in the AKI mice did not change significantly compared to the normal group.
      Conclusions Circulating miR-205 from the cochlea, after ototoxic damage, migrates
      through the blood vessels to organs, which is then finally found in blood. In
      conditions of hearing impairment with ototoxic medications, detection of
      circulating miR-205 in the blood can be used to determine the extent of hearing
      loss. In the future, inner ear damage can be identified by simply performing a
      blood test before the hearing impairment due to ototoxic drugs.

PMID- 30235836
TI  - Salidroside Improves Bone Histomorphology and Prevents Bone Loss in
      Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio.
AB  - Postmenopausal diabetic women have a high risk of fractures. Salidroside has
      preventive effects on estrogen deficiency-induced osteoporosis and has
      hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits
      bone loss in postmenopausal diabetic patients is still unknown. Here, we
      established a rat model of osteoporosis to investigate the protective effects of
      salidroside on bone loss induced by ovariectomy combined with diabetes, also
      investigating the underlying mechanisms. Two-month-old female Sprague-Dawley rats
      were divided into three equal groups (10 rats in each group): control group (with
      sham operation, treated with drug vehicle); OVX/T1DM group (ovariectomized
      diabetic rats); OVX/T1DM-SAL group, comprising ovariectomized diabetic rats
      treated with salidroside (20 mg/kg body weight) by gavage. The results showed
      that after 60 consecutive days of treatment, the bone mineral density (BMD) of
      OVX/T1DM-SAL increased significantly compared with the OVX/T1DM group (p < 0.01).
      The level of serum bone turnover markers, including alkaline phosphatase (ALP),
      cross linked c-telopeptide of type I collagen (CTX-1), osteocalcin, N-terminal
      propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase
      5b (TRACP 5b) were all increased in the OVX/T1DM group compared with the control
      (p < 0.01), and those were decreased by salidroside treatment. Meanwhile, the
      bone histopathological changes were also attenuated, and the bone marrow
      adipogenesis was inhibited in salidroside treated rats. Moreover, protein and
      mRNA ratio of bone osteoprotegerin (OPG)/receptor activator of nuclear factor
      kappaB ligand (RANKL) was upregulated in ovariectomized diabetic rats by
      salidroside treatment. The results above indicated that the protective effect of
      salidroside on bone loss induced by ovariectomy and diabetes was mainly due to
      its ability to suppress bone turnover, inhibit bone marrow adipogenesis, and up
      regulate the OPG/RANKL ratio.

PMID- 30235839
TI  - Large-Strain Hyperelastic Constitutive Model of Envelope Material under Biaxial
      Tension with Different Stress Ratios.
AB  - This paper reports the biaxial tensile mechanical properties of the envelope
      material through experimental and constitutive models. First, the biaxial tensile
      failure tests of the envelope material with different stress ratio in warp and
      weft directions are carried out. Then, based on fiber-reinforced continuum
      mechanics theory, an anisotropic hyperelastic constitutive model on envelope
      material with different stress ratio is developed. A strain energy function that
      characterizes the anisotropic behavior of the envelope material is decomposed
      into three parts: fiber, matrix and fiber-fiber interaction. The fiber-matrix
      interaction is eliminated in this model. A new simple model for fiber-fiber
      interaction with different stress ratio is developed. Finally, the results show
      that the constitutive model has a good agreement with the experiment results. The
      results can be used to provide a reference for structural design of envelope
      material.

PMID- 30235838
TI  - A Statistical Method for Observing Personal Diploid Methylomes and Transcriptomes
      with Single-Molecule Real-Time Sequencing.
AB  - We address the problem of observing personal diploid methylomes, CpG methylome
      pairs of homologous chromosomes that are distinguishable with respect to phased
      heterozygous variants (PHVs), which is challenging due to scarcity of PHVs in
      personal genomes. Single molecule real-time (SMRT) sequencing is promising as it
      outputs long reads with CpG methylation information, but a serious concern is
      whether reliable PHVs are available in erroneous SMRT reads with an error rate of
      ~15%. To overcome the issue, we propose a statistical model that reduces the
      error rate of phasing CpG site to 1%, thereby calling CpG hypomethylation in each
      haplotype with >90% precision and sensitivity. Using our statistical model, we
      examined GNAS complex locus known for a combination of maternally, paternally, or
      biallelically expressed isoforms, and observed allele-specific methylation
      pattern almost perfectly reflecting their respective allele-specific expression
      status, demonstrating the merit of elucidating comprehensive personal diploid
      methylomes and transcriptomes.

PMID- 30235837
TI  - Molecular Communication of a Dying Neuron in Stroke.
AB  - When a main artery of the brain occludes, a cellular response involving multiple
      cell types follows. Cells directly affected by the lack of glucose and oxygen in
      the neuronal core die by necrosis. In the periphery surrounding the ischemic core
      (the so-called penumbra) neurons, astrocytes, microglia, oligodendrocytes,
      pericytes, and endothelial cells react to detrimental factors such as
      excitotoxicity, oxidative stress, and inflammation in different ways. The fate of
      the neurons in this area is multifactorial, and communication between all the
      players is important for survival. This review focuses on the latest research
      relating to synaptic loss and the release of apoptotic bodies and other
      extracellular vesicles for cellular communication in stroke. We also point out
      possible treatment options related to increasing neuronal survival and
      regeneration in the penumbra.

PMID- 30235840
TI  - HSV-Induced Systemic Inflammation as an Animal Model for Behcet's Disease and
      Therapeutic Applications.
AB  - Behcet's disease (BD) affects multiple organs. It is mainly characterized by
      recurrent oral, skin, and genital aphthous ulcers, and eye involvement.
      Successful management of BD is increasing, although its etiology remains unclear.
      A number of etiologies have been proposed, including environmental, genetic,
      viral, and immunological factors. To understand its complex etiology and improve
      its management, animal models of BD have been used to enable more effective
      therapeutic applications with increased clinical significance. An herpes simplex
      virus (HSV) type 1-induced BD mouse model has shown disease characteristics
      similar to those seen in BD patients. An HSV-induced BD animal model has been
      used to test various therapeutic modalities. The applied modalities are several
      materials that are derived from natural products, conventional therapeutics, and
      possible biologics. In this review, we provided how they regulate inflammation in
      an HSV-induced BD model.

PMID- 30235841
TI  - Baculovirus as a Tool for Gene Delivery and Gene Therapy.
AB  - Based on its ability to express high levels of protein, baculovirus has been
      widely used for recombinant protein production in insect cells for more than
      thirty years with continued technical improvements. In addition, baculovirus has
      been successfully applied for foreign gene delivery into mammalian cells without
      any viral replication. However, several CpG motifs are present throughout
      baculoviral DNA and induce an antiviral response in mammalian cells, resulting in
      the production of pro-inflammatory cytokines and type I interferon through a Toll
      like receptor (TLR)-dependent or -independent signaling pathway, and ultimately
      limiting the efficiency of transgene expression. On the other hand, by taking
      advantage of this strong adjuvant activity, recombinant baculoviruses encoding
      neutralization epitopes can elicit protective immunity in mice. Moreover,
      immunodeficient cells, such as hepatitis C virus (HCV)- or human immunodeficiency
      virus (HIV)-infected cells, are more susceptible to baculovirus infection than
      normal cells and are selectively eliminated by the apoptosis-inducible
      recombinant baculovirus. Here, we summarize the application of baculovirus as a
      gene expression vector and the mechanism of the host innate immune response
      induced by baculovirus in mammalian cells. We also discuss the future prospects
      of baculovirus vectors.

PMID- 30235842
TI  - Stress Ratio and Notch Effects on the Very High Cycle Fatigue Properties of a
      Near-Alpha Titanium Alloy.
AB  - Ultrasonic fatigue tests up to 1010 cycles were performed on a turbine engine
      titanium alloy (Ti-8Al-1Mo-1V) at the stress ratio (R) of -1 with smooth
      specimens and at R = -1, 0.1 and 0.5 with notched specimens. As a result, with
      increase of fatigue life, the source of reduced fatigue life caused by multi
      point surface crack initiation changes from crack propagation stage to crack
      initiation stage in the high cycle fatigue regime. Notch effect further promotes
      the degeneration of high cycle and very high cycle fatigue strength at R > -1.
      The bilinear model, extended from the Goodman method, can better estimate the
      mean stress sensitivity of this titanium alloy. The fatigue mean stress
      sensitivity and fatigue-creep mean stress sensitivity of this material increased
      with the increase of fatigue life. The new model, based on the Murakami model,
      can provide more appropriate predictions for notch fatigue strength.

PMID- 30235843
TI  - Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-kappaB
      Signaling Pathway in the Hepatocytes of NAFLD Rats.
AB  - Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often
      used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study
      aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats
      with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into
      eight groups: normal group (NG), model group (MG), low-dose Chaihu-Shugan-San
      group (L-CG), high-dose Chaihu-Shugan-San group (H-CG), low-dose Shenling-Baizhu
      San group (L-SG), high-dose Shenling-Baizhu-San group (H-SG), low dose of
      integrated-recipes group (L-IG), and high dose of integrated-recipes group (H
      IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in
      serum were detected. The serum levels of inflammatory factors including
      interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were
      analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic
      pathological changes were observed with hematoxylin-eosin (HE) and oil red O
      staining. The expression of the p38 mitogen-activated protein kinases
      (MAPK)/nuclear factor-kappaB (NF-kappaB) pathway was detected by quantitative
      real-time PCR and Western blotting. Results: A pathological section revealed that
      NAFLD rats have been successfully reproduced. Compared with the model group, each
      treatment group had different degrees of improvement. The Shugan-Jianpi recipe
      can inhibit the serum levels of IL-1beta, IL-6, and TNF-alpha in NAFLD rats. The
      expression of mRNA and a protein related to the p38 MAPK/NF-kappaB signaling
      pathway were markedly decreased as a result of the Shugan-Jianpi recipe.
      Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its
      mechanism may be related to the suppression of the p38 MAPK/NF-kappaB signaling
      pathway in hepatocytes.

PMID- 30235844
TI  - NovaGenesis Applied to Information-Centric, Service-Defined, Trustable IoT/WSAN
      Control Plane and Spectrum Management.
AB  - We integrate, for the first time in the literature, the following ingredients to
      deal with emerging dynamic spectrum management (DSM) problem in heterogeneous
      wireless sensors and actuators networks (WSANs), Internet of things (IoT) and Wi
      Fi: (i) named-based routing to provide provenance and location-independent access
      to control plane; (ii) temporary storage of control data for efficient and
      cohesive control dissemination, as well as asynchronous communication between
      software-controllers and devices; (iii) contract-based control to improve trust
      ability of actions; (iv) service-defined configuration of wireless devices,
      approximating their configurations to real services needs. The work is
      implemented using NovaGenesis architecture and a proof-of-concept is evaluated in
      a real scenario, demonstrating our approach to automate radio frequency channel
      optimization in Wi-Fi and IEEE 802.15.4 networks in the 2.4 GHz bands. An
      integrated cognitive radio system provides the dual-mode best channel indications
      for novel DSM services in NovaGenesis. By reconfiguring Wi-Fi/IoT devices to best
      channels, the proposed solution more than doubles the network throughput, when
      compared to the case of mutual interference. Therefore, environments equipped
      with the proposal provide enhanced performance to their users.

PMID- 30235845
TI  - Relative Protein Intake and Physical Function in Older Adults: A Systematic
      Review and Meta-Analysis of Observational Studies.
AB  - (1) Background: The present work aims to conduct a systematic review and meta
      analysis of observational studies, in order to investigate the association of
      relative protein intake and physical function in older adults; (2) Methods:
      Observational studies, that investigated the association between protein intake
      and physical function in older adults, were retrieved from MEDLINE, SCOPUS,
      CINAHL, AgeLine, EMBASE, and Cochrane-CENTRAL. Two independent researchers
      conducted study selection and data extraction; (3) Results: Very high protein
      intake (>=1.2 g/kg/day) and high protein intake (>=1.0 g/kg/day) groups showed
      better lower limb physical functioning and walking speed (WS) performance,
      respectively, in comparison to individuals who present relative low protein
      (<0.80 g/kg/day) intake. On the other hand, relative high protein intake does not
      seem to propitiate a better performance on isometric handgrip (IHG) and chair
      rise in comparison to relative low protein intake. In addition, there were no
      significant differences in the physical functioning of high and middle protein
      intake groups; (4) Conclusions: In conclusion, findings of the present study
      indicate that a very high (>=1.2 g/kg/day) and high protein intake (>=1.0
      g/kg/day) are associated with better lower-limb physical performance, when
      compared to low protein (<0.80 g/kg/day) intake, in community-dwelling older
      adults. These findings act as additional evidence regarding the potential need to
      increase protein guidelines to above the current recommendations. However, large
      randomized clinical trials are needed to confirm the addictive effects of high
      protein diets (>=1.0 g/kg/day) in comparison to the current recommendations on
      physical functioning. All data are available in the Open ScienceFramework.

PMID- 30235846
TI  - 1D Mathematical Modelling of Non-Stationary Ion Transfer in the Diffusion Layer
      Adjacent to an Ion-Exchange Membrane in Galvanostatic Mode.
AB  - The use of the Nernst-Planck and Poisson (NPP) equations allows computation of
      the space charge density near solution/electrode or solution/ion-exchange
      membrane interface. This is important in modelling ion transfer, especially when
      taking into account electroconvective transport. The most solutions in literature
      use the condition setting a potential difference in the system (potentiostatic or
      potentiodynamic mode). However, very often in practice and experiment (such as
      chronopotentiometry and voltammetry), the galvanostatic/galvanodynamic mode is
      applied. In this study, a depleted stagnant diffusion layer adjacent to an ion
      exchange membrane is considered. In this article, a new boundary condition is
      proposed, which sets a total current density, i, via an equation expressing the
      potential gradient as an explicit function of i. The numerical solution of the
      problem is compared with an approximate solution, which is obtained by a
      combination of numerical solution in one part of the diffusion layer (including
      the electroneutral region and the extended space charge region, zone (I) with an
      analytical solution in the other part (the quasi-equilibrium electric double
      layer (EDL), zone (II). It is shown that this approach (called the "zonal" model)
      allows reducing the computational complexity of the problem tens of times without
      significant loss of accuracy. An additional simplification is introduced by
      neglecting the thickness of the quasi-equilibrium EDL in comparison to the
      diffusion layer thickness (the "simplified" model). For the first time, the
      distributions of concentrations, space charge density and current density along
      the distance to an ion-exchange membrane surface are computed as functions of
      time in galvanostatic mode. The calculation of the transition time, tau, for an
      ion-exchange membrane agree with an experiment from literature. It is suggested
      that rapid changes of space charge density, and current density with time and
      distance, could lead to lateral electroosmotic flows delaying depletion of near
      surface solution and increasing tau.

PMID- 30235847
TI  - Autologous Transplantation for Older Adults with AML.
AB  - While the majority of patients with acute myeloid leukemia (AML) are above the
      age of 65 years at diagnosis, the outcome of older AML patients remains
      disappointing. Even if standard intensive chemotherapy induces morphologic
      complete remission (CR1), relapses in older AML patients are common leading to
      poor long-term survival outcomes. Since autologous hematopoietic stem cell
      transplantation (HCT) offers distinct anti-leukemic effectiveness while avoiding
      graft-versus-host disease associated with allogeneic transplantation, it
      represents an option for consolidation treatment in selected older AML patients.
      However, prospective studies in older AML patients assessing the benefit of
      autologous HCT compared to chemotherapy consolidation or allogeneic
      transplantation are lacking. Consequently, clinicians face the dilemma that there
      is considerable ambiguity on the most appropriate consolidation treatment for
      older AML patients in CR1. This review highlights the possible role of autologous
      HCT for consolidation in older AML patients reaching CR1 after induction
      treatment.

PMID- 30235848
TI  - Chalcone Derivatives 4'-Amino-1-Naphthyl-Chalcone (D14) and 4'-Amino-4-Methyl-1
      Naphthyl-Chalcone (D15) Suppress Migration and Invasion of Osteosarcoma Cells
      Mediated by p53 Regulating EMT-Related Genes.
AB  - Osteosarcoma (OS) is a primary malignant bone tumor that mainly affects children,
      adolescents, and young adults. The inhibition of metastasis is a main strategy of
      OS therapy since the development of metastatic disease due to drug resistance
      remains the most important cause of death from this cancer. Considering the
      severe side effects of current OS chemotherapy, the identification of anti
      metastatic drugs with reduced toxicity is of great interest. Chalcones are
      polyphenols with a basic structure consisting of an alpha-, beta-unsaturated
      carbonyl system linking two aryl rings. These compounds exhibit anticancer
      activity against a variety of tumor cell lines through multiple mechanisms,
      including the regulation of the tumor-suppressor protein p53 and its target
      genes. An important process regulated by p53 is epithelial-mesenchymal transition
      (EMT), which facilitates tumor metastasis by conferring migratory and invasive
      properties to cancer cells. The activation of p53 can revert EMT and reduce
      migration and invasion. This study aimed to examine the inhibitory effects of two
      4'-aminochalcones on the migration/invasion of the U2OS (p53+/+) and SAOS-2 (p53
      /-) OS cell lines as well as the underlying molecular mechanisms. Cell viability
      was examined by MTT assay. Transwell assays were used to evaluate the migratory
      and invasive ability of the cells. The two 4'-aminochalcones showed low capacity
      to inhibit the viability of OS cells independent of p53 status, but
      preferentially suppressed the migration of U2OS cells and of a SAOS-2 cell line
      expressing p53. Invasion was strongly inhibited by both chalcones independent of
      p53 status. RT-PCR, zymography, and Western blot were used to study the
      expression of matrix metalloproteinases and EMT markers after treatment with the
      chalcones. The results indicated that the 4'-aminochalcone-induced antimigratory
      and anti-invasive effects are potentially associated with the inhibition of
      extracellular matrix (ECM) enzymatic degradation in OS cells and with the
      modulation of EMT genes. These effects probably result from the induced increase
      of p53 protein expression by the two chalcones. In conclusion, chalcones D14 and
      D15 have potential anti-metastatic activity mediated by p53 that can be exploited
      for OS treatment.

PMID- 30235849
TI  - Combined Before-and-After Workplace Intervention to Promote Healthy Lifestyles in
      Healthcare Workers (STI-VI Study): Short-Term Assessment.
AB  - Health care workers (HCWs) are prone to a heavy psycho-physical workload. Health
      promotion programs can help prevent the onset of chronic and work-related
      diseases. The aim of the STI-VI 'before-and-after' study, with assessments
      scheduled at 6 and 12 months, was to improve the lifestyle of HCWs with at least
      one cardiovascular risk factor. A tailored motivational counseling intervention,
      focusing on dietary habits and physical activity (PA) was administered to 167
      HCWs (53 males; 114 females). BMI, waist circumference, blood pressure, and
      cholesterol, triglyceride, and blood glucose levels were measured before and
      after the intervention. The 6-month results (total sample and by gender) showed a
      marked effect on lifestyle: PA improved (+121.2 MET, p = 0.01), and diets became
      more similar to the Mediterranean model (+0.8, p < 0.001). BMI dropped (-0.2, p <
      0.03), and waist circumference improved even more (-2.5 cm; p < 0.001). Other
      variables improved significantly: total and LDL cholesterol (-12.8 and -9.4
      mg/dL, p < 0.001); systolic and diastolic blood pressure (-4.4 and -2.5 mmHg, p <
      0.001); blood glucose (-1.5 mg/dL, p = 0.05); and triglycerides (significant only
      in women), (-8.7 mg/dL, p = 0.008); but HDL cholesterol levels dropped too. If
      consolidated at 12 months, these results indicate that our intervention can help
      HCWs maintain a healthy lifestyle and work ability.

PMID- 30235850
TI  - Hydrogen Peroxide Generation of Copper/Ascorbate Formulations on Cotton: Effect
      on Antibacterial and Fibroblast Activity for Wound Healing Application.
AB  - Greige cotton (unbleached cotton) is an intact plant fiber that retains much of
      the outer cotton fiber layers. These layers contain pectin, peroxidases, and
      trace metals that are associated with hydrogen peroxide (H2O2) generation during
      cotton fiber development. When greige cotton is subjected to a nonwoven
      hydroentanglement process, components of the outer cotton fiber layers are
      retained. When hydrated, this fabric can generate H2O2 (5-50 micromolar). This
      range has been characterized as inducing accelerated wound healing associated
      with enhanced cell signaling and the proliferation of cells vital to wound
      restoration. On the other hand, H2O2 levels above 50 micromolar have been
      associated with bacteriostatic activity. Here, we report the preparation and
      hydrogen peroxide activity of copper/ascorbate formulations, both as adsorbed and
      in situ synthesized analogs on cotton. The cooper/ascorbate-cotton formulations
      were designed with the goal of modulating hydrogen peroxide levels within
      functional ranges beneficial to wound healing. The cotton/copper formulation
      analogs were prepared on nonwoven unbleached cotton and characterized with cotton
      impregnation titers of 3-14 mg copper per gram of cotton. The copper/ascorbate
      cotton analog formulations were characterized spectroscopically, and the copper
      titer was quantified with ICP analysis and probed for peroxide production through
      assessment with Amplex Red. All analogs demonstrated antibacterial activity.
      Notably, the treatment of unbleached cotton with low levels of ascorbate (~2 mg/g
      cotton) resulted in a 99 percent reduction in Klebsiella pneumoniae and
      Staphylococcus aureus. In situ synthesized copper/ascorbate nanoparticles
      retained activity and did not leach out upon prolonged suspension in an aqueous
      environment. An assessment of H2O2 effects on fibroblast proliferation are
      discussed in light of the copper/cotton analogs and wound healing.

PMID- 30235851
TI  - Reduced Graphene Oxide-Based Double Network Polymeric Hydrogels for Pressure and
      Temperature Sensing.
AB  - We demonstrate the fabrication of novel reduced graphene oxide (rGO)-based double
      network (DN) hydrogels through the polymerization of poly(N-isopropylacrylamide)
      (PNIPAm) and carboxymethyl chitosan (CMC). The facile synthesis of DN hydrogels
      includes the reduction of graphene oxide (GO) by CMC, and the subsequent
      polymerization of PNIPAm. The presence of rGO in the fabricated PNIPAm/CMC/rGO DN
      hydrogels enhances the compressibility and flexibility of hydrogels with respect
      to pure PNIPAm hydrogels, and they exhibit favorable thermoresponsivity,
      compressibility, and conductivity. The created hydrogels can be continuously
      cyclically compressed and have excellent bending properties. Furthermore, it was
      found that the hydrogels are pressure- and temperature-sensitive, and can be
      applied to the design of both pressure and temperature sensors to detect
      mechanical deformation and to measure temperature. Our preliminary results
      suggest that these rGO-based DN hydrogels exhibit a high potential for the
      fabrication of soft robotics and artificially intelligent skin-like devices.

PMID- 30235852
TI  - Assessment of Migration of Human MSCs through Fibrin Hydrogels as a Tool for
      Formulation Optimisation.
AB  - Control of cell migration is fundamental to the performance of materials for cell
      delivery, as for cells to provide any therapeutic effect, they must migrate out
      from the delivery material. Here the influence of fibrinogen concentration on the
      migration of encapsulated human mesenchymal stem cells (hMSCs) from a cell
      spheroid through fibrin hydrogels is tracked over time. Fibrin was chosen as a
      model material as it is routinely employed as a haemostatic agent and more
      recently has been applied as a localised delivery vehicle for potential
      therapeutic cell populations. The hydrogels consisted of 5 U/mL thrombin and
      between 5 and 50 mg/mL fibrinogen. Microstructural and viscoelastic properties of
      different compositions were evaluated using SEM and rheometry. Increasing the
      fibrinogen concentration resulted in a visibly denser matrix with smaller pores
      and higher stiffness. hMSCs dispersed within the fibrin gels maintained cell
      viability post-encapsulation, however, the migration of cells from an
      encapsulated spheroid revealed that denser fibrin matrices inhibit cell
      migration. This study provides the first quantitative study on the influence of
      fibrinogen concentration on 3D hMSC migration within fibrin gels, which can be
      used to guide material selection for scaffold design in tissue engineering and
      for the clinical application of fibrin sealants.

PMID- 30235854
TI  - Wireless Sensor Networks for Long-Term Monitoring of Urban Noise.
AB  - Noise pollution in urban environments is becoming increasingly common and it has
      potential to negatively impact people's health and decrease overall productivity.
      In order to alleviate these effects, it is important to better quantify noise
      patterns and levels through data collection and analysis. Wireless sensor
      networks offer a method for achieving this with a higher level of granularity
      than traditional handheld devices. In this study, a wireless sensing unit (WSU)
      was developed that possesses the same functionality as a handheld sound level
      meter. The WSU is comprised of a microcontroller unit that enables on-board
      computations, a wireless transceiver that uses Zigbee protocol for data
      transmission, and an external peripheral board that houses the microphone
      transducer. The WSU utilizes on-board data processing techniques to monitor noise
      by computing equivalent continuous sound levels, LeqT, which effectively
      minimizes data transmission and increases the overall longevity of the node.
      Strategies are also employed to ensure real-time functionality is maintained on
      the sensing unit, with a focus on preventing bottlenecks between data
      acquisition, data processing, and wireless transmission. Four units were deployed
      in two weeks field validation test and were shown to be capable of monitoring
      noise for extended periods of time.

PMID- 30235853
TI  - Robust Innate Immunity of Young Rabbits Mediates Resistance to Rabbit Hemorrhagic
      Disease Caused by Lagovirus Europaeus GI.1 But Not GI.2.
AB  - The rabbit caliciviruses Lagovirus europaeus GI.1 and GI.2 both cause acute
      necrotizing hepatitis in European rabbits (Oryctolagus cuniculus). Whilst GI.2 is
      highly virulent in both young and adult rabbits, rabbits younger than eight weeks
      of age are highly resistant to disease caused by GI.1, although they are still
      permissive to infection and viral replication. To investigate the underlying
      mechanism(s) of this age related resistance to GI.1, we compared liver
      transcriptomes of young rabbits infected with GI.1 to those of adult rabbits
      infected with GI.1 and young rabbits infected with GI.2. Our data suggest that
      kittens have constitutively heightened innate immune responses compared to adult
      rabbits, particularly associated with increased expression of major
      histocompatibility class II molecules and activity of natural killer cells,
      macrophages, and cholangiocytes. This enables them to respond more rapidly to
      GI.1 infection than adult rabbits and thus limit virus-induced pathology. In
      contrast, these responses were not fully developed during GI.2 infection. We
      speculate that the observed downregulation of multiple genes associated with
      innate immunity in kittens during GI.2 infection may be due to virally-mediated
      immunomodulation, permitting fatal disease to develop. Our study provides insight
      into the fundamental host-pathogen interactions responsible for the differences
      in age-related susceptibility, which likely plays a critical role in defining the
      success of GI.2 in outcompeting GI.1 in the field.

PMID- 30235856
TI  - Indirect Microcontact Printing to Create Functional Patterns of Physisorbed
      Antibodies.
AB  - Microcontact printing (uCP) is a practical and versatile approach to create
      nanostructured patterns of biomolecular probes, but it involves conformational
      changes on the patterned bioreceptors that often lead to a loss on the biological
      activity of the resulting structures. Herein we introduce indirect uCP to create
      functional patterns of bioreceptors on solid substrates. This is a simple
      strategy that relies on physisorbing biomolecular probes of interest in the
      nanostructured gaps that result after patterning backfilling agents by standard
      uCP. This study presents the approach, assesses bovine serum albumin as
      backfilling agent for indirect uCP on different materials, reports the
      limitations of standard uCP on the functionality of patterned antibodies, and
      demonstrates the capabilities of indirect uCP to solve this issue. Bioreceptors
      were herein structured as diffractive gratings and used to measure biorecognition
      events in label-free conditions. Besides, as a preliminary approach towards
      sensing biomarkers, this work also reports the implementation of indirect uCP in
      an immunoassay to detect human immunoglobulin E.

PMID- 30235857
TI  - An Invisible Salient Landmark Approach to Locating Pedestrians for Predesigned
      Business Card Route of Pedestrian Navigation.
AB  - Visual landmarks are important navigational aids for research into and design of
      applications for last mile pedestrian navigation, e.g., business card route of
      pedestrian navigation. The business card route is a route between a fixed origin
      (e.g., campus entrance) to a fixed destination (e.g., office). The changing
      characteristics and combinations of various sensors' data in smartphones or
      navigation devices can be viewed as invisible salient landmarks for business card
      route of pedestrian navigation. However, the advantages of these invisible
      landmarks have not been fully utilized, despite the prevalence of GPS and digital
      maps. This paper presents an improvement to the Dempster-Shafer theory of
      evidence to find invisible landmarks along predesigned pedestrian routes, which
      can guide pedestrians by locating them without using digital maps. This approach
      is suitable for use as a "business card" route for newcomers to find their last
      mile destinations smoothly by following precollected sensor data along a target
      route. Experiments in real pedestrian navigation environments show that our
      proposed approach can sense the location of pedestrians automatically, both
      indoors and outdoors, and has smaller positioning errors than purely GPS and Wi
      Fi positioning approaches in the study area. Consequently, the proposed
      methodology is appropriate to guide pedestrians to unfamiliar destinations, such
      as a room in a building or an exit from a park, with little dependency on
      geographical information.

PMID- 30235858
TI  - Study of Almond Shell Characteristics.
AB  - A large amount of almond shells are disposed of every year. The anatomical and
      chemical characteristics of almond shells are investigated in this paper in order
      to contribute to better utilization of these shells. The micromorphology, surface
      elements, thermal stability, crystallization, chemical composition, and relative
      properties of almond shells are analyzed. Under observation by microscope and
      electron microscope, the diameter of almond shells is 300-500 MUm for large
      holes, and 40-60 MUm for small holes present in the shell. X-ray photoelectron
      spectroscopy shows the elements of almond shells include C (72.27%), O (22.88%),
      N (3.87%), and Si (0.87%). The main chemical constituents of cellulose,
      hemicellulose and lignin in almond shells account for 38.48%, 28.82% and 29.54%,
      respectively. The alkaline extract content of almond shells is 14.03%, and
      benzene alcohol extraction is 8.00%. The benzene alcohol extractives of almond
      shells mainly contain 17 types of organic compound, including benzene ring,
      ethylene, carbon three bond, and other mufti-functional groups. Thermal stability
      analysis shows almond shells mainly lose weight at 260  degrees C and 335 
      degrees C. These characteristics indicate that almond shells have the capacity to
      be used in composites and absorption materials.

PMID- 30235855
TI  - Antioxidative 1,4-Dihydropyridine Derivatives Modulate Oxidative Stress and
      Growth of Human Osteoblast-Like Cells In Vitro.
AB  - Oxidative stress has been implicated in pathophysiology of different human stress
      and age-associated disorders, including osteoporosis for which antioxidants
      could be considered as therapeutic remedies as was suggested recently. The 1,4
      dihydropyridine (DHP) derivatives are known for their pleiotropic activity, with
      some also acting as antioxidants. To find compounds with potential antioxidative
      activity, a group of 27 structurally diverse DHPs, as well as one pyridine
      compound, were studied. A group of 11 DHPs with 10-fold higher antioxidative
      potential than of uric acid, were further tested in cell model of human
      osteoblast-like cells. Short-term combined effects of DHPs and 50 uM H2O2 (1-h
      each), revealed better antioxidative potential of DHPs if administered before a
      stressor. Indirect 24-h effect of DHPs was evaluated in cells further exposed to
      mild oxidative stress conditions induced either by H2O2 or tert-butyl
      hydroperoxide (both 50 uM). Cell growth (viability and proliferation), generation
      of ROS and intracellular glutathione concentration were evaluated. The promotion
      of cell growth was highly dependent on the concentrations of DHPs used, type of
      stressor applied and treatment set-up. Thiocarbatone III-1, E2-134-1 III-4,
      Carbatone II-1, AV-153 IV-1, and Diethone I could be considered as therapeutic
      agents for osteoporosis although further research is needed to elucidate their
      bioactivity mechanisms, in particular in respect to signaling pathways involving
      4-hydroxynoneal and related second messengers of free radicals.

PMID- 30235860
TI  - Clinical Significance of Phase Angle in Non-Dialysis CKD Stage 5 and Peritoneal
      Dialysis Patients.
AB  - BACKGROUND: Fluid overload and protein-energy wasting (PEW) are common in
      patients with end-stage renal disease (ESRD) and lead to a poor prognosis. We
      aimed to evaluate the volume and nutritional status of ESRD patients and to
      determine the clinical significance of phase angle (PhA). METHODS: This study was
      a cross-sectional comparison of bioimpedance spectroscopy (BIS) findings in
      patients with non-dialysis chronic kidney disease (CKD) stage 5 (CKD5-ND, N = 80)
      and age/sex-matched peritoneal dialysis patients (PD, N = 80). PEW was defined as
      a PhA less than 4.5 degrees . RESULTS: The PhA was found to be positively
      associated with a geriatric nutritional risk index (GNRI, r = 0.561, p < 0.001),
      lean tissue index (LTI, r = 0.473, p < 0.001), and albumin (r = 0.565, p < 0.001)
      while OH/ECW (r = -0.824, p < 0.001) showed an inverse correlation. The CKD5-ND
      group had more overhydration (p = 0.027). The PD group had significantly higher
      PhA (p = 0.023), GNRI (p = 0.005), hemoglobin (p < 0.001), and albumin (p =
      0.003) than the CKD5-ND group. The cut-off values predicting PEW were found to be
      3.55 g/dL for albumin, 94.9 for GNRI, and 12.95 kg/m2 for LTI in PD patients.
      CONCLUSIONS: This study demonstrated that PhA could be used as a marker to
      reflect nutritional status in patients with ESRD. Since BIS can inform both
      volume and nutritional status, regular monitoring will provide the basis for
      active correction of fluid overload and nutritional supplementation, which may
      improve outcomes in patients with ESRD.

PMID- 30235861
TI  - Carbon-Related Defects as a Source for the Enhancement of Yellow Luminescence of
      Unintentionally Doped GaN.
AB  - Yellow luminescence (YL) of unintentionally doped GaN (u-GaN) peaking at about
      2.2 eV has been investigated for decades, but its origin still remains
      controversial. In this study, ten u-GaN samples grown via metalorganic chemical
      vapor deposition (MOCVD) are investigated. It is observed from the room
      temperature (RT) photoluminescence (PL) measurements that the YL band is enhanced
      in the PL spectra of those samples if their MOCVD growth is carried out with a
      decrease of pressure, temperature, or flow rate of NH3. Furthermore, a strong
      dependence of YL band intensity on the carbon concentration is found by secondary
      ion mass spectroscopy (SIMS) measurements, demonstrating that the increased
      carbon-related defects in these samples are responsible for the enhancement of
      the YL band.

PMID- 30235859
TI  - Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-beta1-Induced
      Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial
      Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling ?.
AB  - The antifibrotic potential of platelet-rich plasma (PRP) is controversial. This
      study examined the effects of PRP on in vitro transforming growth factor (TGF)
      beta1-induced differentiation of fibroblasts into myofibroblasts, the main
      drivers of fibrosis, and the involvement of vascular endothelial growth factor
      (VEGF)-A in mediating PRP-induced responses. The impact of PRP alone on
      fibroblast differentiation was also assessed. Myofibroblastic phenotype was
      evaluated by confocal fluorescence microscopy and western blotting analyses of
      alpha-smooth muscle actin (sma) and type-1 collagen expression, vinculin-rich
      focal adhesion clustering, and stress fiber assembly. Notch-1, connexin 43, and
      VEGF-A expression were also analyzed by RT-PCR. PRP negatively regulated
      fibroblast-myofibroblast transition via VEGF-A/VEGF receptor (VEGFR)-1-mediated
      inhibition of TGF-beta1/Smad3 signaling. Indeed TGF-beta1/PRP co-treated
      fibroblasts showed a robust attenuation of the myofibroblastic phenotype
      concomitant with a decrease of Smad3 expression levels. The VEGFR-1 inhibition by
      KRN633 or blocking antibodies, or VEGF-A neutralization in these cells prevented
      the PRP-promoted effects. Moreover PRP abrogated the TGF-beta1-induced reduction
      of VEGF-A and VEGFR-1 cell expression. The role of VEGF-A signaling in
      counteracting myofibroblast generation was confirmed by cell treatment with
      soluble VEGF-A. PRP as single treatment did not induce fibroblast
      myodifferentiation. This study provides new insights into cellular and molecular
      mechanisms underpinning PRP antifibrotic action.

PMID- 30235862
TI  - Activity-Friendly Built Environments in a Super-Aged Society, Japan: Current
      Challenges and toward a Research Agenda.
AB  - There is a growing recognition of the role of built environment attributes, such
      as streets, shops, greenways, parks, and public transportation stations, in
      supporting people's active behaviors. In particular, surrounding built
      environments may have an important role in supporting healthy active aging.
      Nevertheless, little is known about how built environments may influence active
      lifestyles in "super-aged societies". More robust evidence-based research is
      needed to identify how where people live influences their active behaviors, and
      how to build beneficial space in the context of super-aged societies. This
      evidence will also be informative for the broader international context, where
      having an aging society will be the inevitable future. This commentary sought to
      move this research agenda forward by identifying key research issues and
      challenges in examining the role of built environment attributes on active
      behaviors in Japan, which is experiencing the longest healthy life expectancy,
      but rapid "super-aging", with the highest proportion of old adults among its
      population in the world.

PMID- 30235863
TI  - GNSS Trajectory Anomaly Detection Using Similarity Comparison Methods for
      Pedestrian Navigation.
AB  - The urban setting is a challenging environment for GNSS receivers. Multipath and
      other anomalies typically increase the positioning error of the receiver.
      Moreover, the error estimate of the position is often unreliable. In this study,
      we detect GNSS trajectory anomalies by using similarity comparison methods
      between a pedestrian dead reckoning trajectory, recorded using a foot-mounted
      inertial measurement unit, and the corresponding GNSS trajectory. During a normal
      walk, the foot-mounted inertial dead reckoning setup is trustworthy up to a few
      tens of meters. Thus, the differing GNSS trajectory can be detected using form
      similarity comparison methods. Of the eight tested methods, the Hausdorff
      distance (HD) and the accumulated distance difference (ADD) give slightly more
      consistent detection results compared to the rest.

PMID- 30235864
TI  - Sleep Quality and Its Associated Factors among Low-Income Adults in a Rural Area
      of China: A Population-Based Study.
AB  - BACKGROUND: There is limited population-based research focusing on sleep quality
      among low-income Chinese adults in rural areas. This study aimed to assess sleep
      quality among low-income adults in a rural area in China and identify the
      association between sleep quality and sociodemographic, lifestyle and health
      related factors. METHODS: The study was conducted from September to November in
      2017 using a cross-sectional survey questionnaire. A total of 6905 participants
      were recruited via multistage, stratified cluster sampling. Data were collected
      using the Chinese versions of Pittsburgh Sleep Quality Index and Food Frequency
      Questionnaire, while we also determined the sociodemographic profiles of the
      participants. RESULTS: The mean age of the sample was 58.71 +/- 14.50 years, with
      59.7% being male, while the mean duration of daily sleep was 5.95 +/- 1.31 h,
      with 56.7% reportedly experiencing poor sleep quality. Multiple regression
      analysis revealed that older age, unemployment, lower income, disability and
      chronic disease comorbidities were significant factors associated with an
      increased risk of poor sleep quality for both genders. Moreover, married and
      higher education level were associated with decreased risk of poor sleep quality
      for females, while a meat-heavy diet and illness during the past two weeks
      increased the risk of poor sleep quality for males. CONCLUSIONS:
      Sociodemographic, lifestyle and health-related factors had an impact on the
      frequently poor sleep quality of low-income Chinese adults in rural areas. Thus,
      comprehensive measures must be developed to address the modifiable predictive
      factors that can possibly enhance sleep quality.

PMID- 30235865
TI  - Transcriptional Control of Honey Bee (Apis mellifera) Major Royal Jelly Proteins
      by 20-Hydroxyecdysone.
AB  - One of the first tasks of worker honey bees (Apis mellifera) during their
      lifetime is to feed the larval offspring. In brief, young workers (nurse bees)
      secrete a special food jelly that contains a large amount of unique major royal
      jelly proteins (MRJPs). The regulation of mrjp gene expression is not well
      understood, but the large upregulation in well-fed nurse bees suggests a tight
      repression until, or a massive induction upon, hatching of the adult worker bees.
      The lipoprotein vitellogenin, the synthesis of which is regulated by the two
      systemic hormones 20-hydroxyecdysone and juvenile hormone, is thought to be a
      precursor for the production of MRJPs. Thus, the regulation of mrjp expression by
      the said systemic hormones is likely. This study focusses on the role of 20
      hydroxyecdysone by elucidating its effect on mrjp gene expression dynamics.
      Specifically, we tested whether 20-hydroxyecdysone displayed differential effects
      on various mrjps. We found that the expression of the mrjps (mrjp1-3) that were
      finally secreted in large amounts into the food jelly, in particular, were down
      regulated by 20-hydroxyecdysone treatment, with mrjp3 showing the highest
      repression value.

PMID- 30235867
TI  - Synthesis and Exploration of the Lubricating Behavior of Nanoparticulated Mo15S19
      in Linseed Oil.
AB  - Molybdenum chalcogenides present interesting properties beyond their
      superconducting critical temperatures and upper critical magnetic fields, making
      them suitable for potential applications in tribology, batteries, catalysis, or
      thermopower. In this study, Mo15S19 nanoparticles with an average diameter of 10
      nm were synthesized via the reaction of ammonium molybdate with hydrochloric acid
      and elemental sulfur as reducers at 245  degrees C. The oxidation to MoO3 in air
      was efficiently avoided by using linseed oil as a reaction medium and dispersant.
      Scanning electron microscopy (SEM) micrographs of the as-prepared samples
      revealed the presence of few-micron-size aggregates, while transmission electron
      microscopy (TEM) characterization evidenced that the samples were
      polynanocrystalline with a high degree of homogeneity in size (standard deviation
      of 2.7 nm). The absence of the first-order (00l) reflection in the X-ray
      diffraction pattern was also indicative of the absence of Mo3S4 stacking,
      suggesting that it was a non-layered material. A dispersion of the nanoparticles
      in linseed oil has been studied as a lubricant of steel-steel sliding contacts,
      showing the formation of a surface layer that reduces wear and mean friction
      coefficients with respect to the base oil.

PMID- 30235866
TI  - Deficiency in STAT1 Signaling Predisposes Gut Inflammation and Prompts Colorectal
      Cancer Development.
AB  - Signal transducer and activator of transcription 1 (STAT1) is part of the Janus
      kinase (JAK/STAT) signaling pathway that controls critical events in intestinal
      immune function related to innate and adaptive immunity. Recent studies have
      implicated STAT1 in tumor-stroma interactions, and its expression and activity
      are perturbed during colon cancer. However, the role of STAT1 during the
      initiation of inflammation-associated cancer is not clearly understood. To
      determine the role of STAT1 in colitis-associated colorectal cancer (CAC), we
      analyzed the tumor development and kinetics of cell recruitment in wild-type WT
      or STAT1-/- mice treated with azoxymethane (AOM) and dextran sodium sulfate
      (DSS). Following CAC induction, STAT1-/- mice displayed an accelerated appearance
      of inflammation and tumor formation, and increased damage and scores on the
      disease activity index (DAI) as early as 20 days after AOM-DSS exposure compared
      to their WT counterparts. STAT1-/- mice showed elevated colonic epithelial cell
      proliferation in early stages of injury-induced tumor formation and decreased
      apoptosis in advanced tumors with over-expression of the anti-apoptotic protein
      Bcl2 at the colon. STAT1-/- mice showed increased accumulation of Ly6G+Ly6C
      CD11b+ cells in the spleen at 20 days of CAC development with concomitant
      increases in the production of IL-17A, IL-17F, and IL-22 cytokines compared to WT
      mice. Our findings suggest that STAT1 plays a role as a tumor suppressor molecule
      in inflammation-associated carcinogenesis, particularly during the very early
      stages of CAC initiation, modulating immune responses as well as controlling
      mechanisms such as apoptosis and cell proliferation.

PMID- 30235868
TI  - Dual Functional Ultrafiltration Membranes with Enzymatic Digestion and Thermo
      Responsivity for Protein Self-Cleaning.
AB  - Controlling surface-protein interaction during wastewater treatment is the key
      motivation for developing functionally modified membranes. A new biocatalytic
      thermo-responsive poly vinylidene fluoride (PVDF)/nylon-6,6/poly(N
      isopropylacrylamide)(PNIPAAm) ultrafiltration membrane was fabricated to achieve
      dual functionality of protein-digestion and thermo-responsive self-cleaning. The
      PVDF/nylon-6,6/PNIPAAm composite membranes were constructed by integrating a
      hydrophobic PVDF cast layer and hydrophilic nylon-6,6/PNIPAAm nanofiber layer on
      to which trypsin was covalently immobilized. The enzyme immobilization density on
      the membrane surface decreased with increasing PNIPAAm concentration, due to the
      decreased number of amine functional sites. An ultrafiltration study was
      performed using the synthetic model solution containing BSA/NaCl/CaCl2, where the
      PNIPAAm containing biocatalytic membranes demonstrated a combined effect of
      enzymatic and thermo-switchable self-cleaning. The membrane without PNIPAAm
      revealed superior fouling resistance and self-cleaning with an RPD of 22%,
      compared to membranes with 2 and 4 wt % PNIPAAm with 26% and 33% RPD,
      respectively, after an intermediate temperature cleaning at 50  degrees C,
      indicating that higher enzyme density offers more efficient self-cleaning than
      the combined effect of enzyme and PNIPAAm at low concentration. The
      conformational volume phase transition of PNIPAAm did not affect the stability of
      immobilized trypsin on membrane surfaces. Such novel surface engineering design
      offer a promising route to mitigate surface-protein contamination in wastewater
      applications.

PMID- 30235869
TI  - Fabrication and Characterization of High-Frequency Ultrasound Transducers Based
      on Lead-Free BNT-BT Tape-Casting Thick Film.
AB  - A lead-free 0.94(Na0.5Bi0.5) TiO3-0.06 BaTiO3 (BNT-BT) thick film, with a
      thickness of 60 MUm, has been fabricated using a tape-casting method. The
      longitudinal piezoelectric constant, clamped dielectric permittivity constant,
      remnant polarization and coercive field of the BNT-BT thick film were measured to
      be 150 pC/N, 1928, 13.6 MUC/cm2, and 33.6 kV/cm, respectively. The
      electromechanical coupling coefficient kt was calculated to be 0.55 according to
      the measured electrical impedance spectrum. A high-frequency plane ultrasound
      transducer was successfully fabricated using a BNT-BT thick film. The performance
      of the transducer was characterized and evaluated by the pulse-echo testing and
      wire phantom imaging operations. The BNT-BT thick film transducer exhibits a
      center frequency of 34 MHz, a -6 dB bandwidth of 26%, an axial resolution of 77
      MUm and a lateral resolution of 484 MUm. The results suggest that lead-free BNT
      BT thick film fabricated by tape-casting method is a promising lead-free
      candidate for high-frequency ultrasonic transducer applications.

PMID- 30235870
TI  - The Effect of Pectinase-Assisted Extraction on the Physicochemical and Biological
      Properties of Polysaccharides from Aster scaber.
AB  - The edible and medicinal perennial herb Aster scaber is known to have anticancer,
      antioxidant, and immunomodulatory properties. However, the biological effects of
      its polysaccharides are not well understood. Here, we aimed to extract novel
      polysaccharides with enhanced biological properties from Aster scaber using
      enzyme-assisted methods. Amylase, cellulase, and pectinase were used to extract
      enzyme-assisted polysaccharide (ASEP)-A, ASEP-C, and ASEP-P, respectively. The
      yields, physicochemical properties, and immunostimulatory activities of the
      polysaccharides were investigated and compared with those of hot water extracted
      polysaccharide (ASWP). The highest yield (3.8%) was achieved for ASEP-P extracted
      using pectinase digestion. Fourier-transform infrared spectroscopy (FT-IR) and
      chemical composition analysis revealed that ASWP and three ASEPs were typical
      acidic heteropolysaccharides, mainly comprising rhamnose, arabinose, galactose,
      glucose, and galacturonic acid. Immunostimulatory activity assays on RAW264.7
      macrophages showed ASEP-P to have the greatest immunostimulatory potential in
      terms of nitric oxide (NO) and cytokine productions and phagocytic activity. ASEP
      P administration improved immune-enhancing effects in normal mice by improving
      the spleen index and splenic lymphocyte proliferation, and in immunosuppressed
      mice by modulating lymphocyte proliferation, natural killer (NK) cell activity,
      and leukocyte counts. The ASEP-P derived from pectinase hydrolysate of Aster
      scaber demonstrated efficacious immunostimulatory properties and has potential
      applications as an immune stimulator.

PMID- 30235873
TI  - Fabrication of Porous Al2O3 Ceramics with Submicron-Sized Pores Using a Water
      Based Gelcasting Method.
AB  - The gelcasting method is usually employed to fabricate relatively dense ceramics.
      In this work, however, porous Al2O3 ceramics with submicron-sized pores were
      fabricated using the water-based gelcasting method by keeping the Al2O3 content
      at low levels. By controlling the water content in the ceramic slurries and the
      sintering temperature of the green samples, the volume fractions and the size
      characteristics of the pores in the porous Al2O3 can be readily obtained. For the
      porous Al2O3 ceramics prepared with 30 vol.% Al2O3 content in the slurries, their
      open porosities were from 38.3% to 47.2%, while their median pore sizes varied
      from 299.8 nm to 371.9 nm. When there was more Al2O3 content in the slurries (40
      vol.% Al2O3), the porous Al2O3 ceramics had open porosities from 37.0% to 46.5%,
      and median pore sizes from 355.4 nm to 363.1 nm. It was found that a higher
      sintering temperature and Al2O3 content in the slurries increased the mechanical
      strength of the porous Al2O3 ceramics.

PMID- 30235872
TI  - Isolation and Identification of Benzochroman and Acylglycerols from Massa
      Medicata Fermentata and Their Inhibitory Effects on LPS-Stimulated Cytokine
      Production in Bone Marrow-Derived Dendritic Cells.
AB  - Massa Medicata Fermentata (MMF), known as Shenqu, is an important traditional
      Chinese medicine widely used to treat indigestion, vomiting, and diarrhea. In
      this study, a new benzochroman, 3(S)-3,4-dihydro-5,10-di-beta-d-glucopyranoside
      2,2-dimethyl-2H-naphtho(2,3-b)pyran-3-ol (1), and five known galactosyl
      acylglycerols (2-6) were isolated from a methanol extract from MMF. In addition,
      their chemical structures were determined by chemical and spectroscopic methods,
      which were compared with the previously reported data. Furthermore, the effects
      of isolated compounds on lipopolysaccharide (LPS)-stimulated bone marrow-derived
      dendritic cells were investigated. Compounds 1-3 exhibited significant inhibitory
      effects on the LPS-induced production of IL-6 and IL-12 p40, with IC50 values
      ranging from 1.6 to 10.2 MUM. Compounds 2 and 3 also exhibited strong inhibitory
      effects on the LPS-stimulated production of TNF-alpha with IC50 values of 12.0
      and 11.2 MUM, respectively. The results might provide a scientific basis for the
      development of the active components in MMF, as well as for novel anti
      inflammatory agents.

PMID- 30235871
TI  - Deep Brain Stimulation Modified Autism-Like Deficits via the Serotonin System in
      a Valproic Acid-Induced Rat Model.
AB  - Deep brain stimulation (DBS) is known to be a promising treatment for resistant
      depression, which acts via the serotonin (5-hydroxytryptamine, 5-HT) system in
      the infralimbic prefrontal cortex (ILPFC). Previous study revealed that
      dysfunction of brain 5-HT homeostasis is related to a valproate (VPA)-induced rat
      autism spectrum disorder (ASD) model. Whether ILPFC DBS rescues deficits in VPA
      induced offspring through the 5-HT system is not known. Using VPA-induced
      offspring, we therefore explored the effect of DBS in autistic phenotypes and
      further investigated the underlying mechanism. Using combined behavioral and
      molecular approaches, we observed that applying DBS and 5-HT1A receptor agonist
      treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) reversed
      sociability deficits, anxiety and hyperactivity in the VPA-exposed offspring. We
      then administered the selective 5-HT1A receptor antagonist N-[2-[4-(2
      Methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate
      (WAY 100635), following which the effect of DBS in terms of improving autistic
      behaviors was blocked in the VPA-exposed offspring. Furthermore, we found that
      both 8-OH-DPAT and DBS treatment rescued autistic behaviors by decreasing the
      expressions of NR2B subunit of N-methyl-D-aspartate receptors (NMDARs) and the
      beta3 subunit of gamma-aminobutyric acid type A receptors (GABAAR) in the PFC
      region. These results provided the first evidence of characteristic behavioral
      changes in VPA-induced offspring caused by DBS via the 5-HT system in the ILPFC.

PMID- 30235874
TI  - Design of Wideband GHz Electric Field Sensor Integrated with Optical Fiber
      Transmission Link for Electromagnetic Pulse Signal Measurement.
AB  - The detection of high frequency overvoltage and partial discharge is of great
      significance in evaluating the insulation condition of high-voltage power
      equipment. A wideband GHz electric field (E-field) sensor for electromagnetic
      pulse (EMP) signal measurement was proposed in this paper. An optical fiber
      transmission link was adopted in the design in order to implement high-voltage
      isolation and reduce electromagnetic interference during transmission. The
      designed sensor was mainly made up of a differential electric field (D-dot)
      antenna, transmitter, and receiver. The D-dot antenna was designed to detect high
      frequency E-field strength and generate a corresponding voltage signal, which was
      converted into an optical signal by the transmitter. The optical signal could be
      transmitted a large distance through an optical fiber without electromagnetic
      interference and changed back to a voltage signal again by a receiver. The design
      process of the sensor was introduced in detail, and experiments were performed
      using a gigahertz transverse electromagnetic (GTEM) cell and an EMP simulator to
      verify it. The results indicated that the designed sensor had a good performance
      besides an expectable delay due to the optional amplifier.

PMID- 30235875
TI  - The Effects of Using Aluminum Oxide Nanoparticles as Heat Transfer Fillers on
      Morphology and Thermal Performances of Form-Stable Phase Change Fibrous Membranes
      Based on Capric-Palmitic-Stearic Acid Ternary Eutectic/Polyacrylonitrile
      Composite.
AB  - In this paper, innovative capric-palmitic-stearic acid ternary
      eutectic/polyacrylonitrile/aluminum oxide (CA-PA-SA/PAN/Al2O3) form-stable phase
      change composite fibrous membranes (PCCFMs) with different mass ratios of Al2O3
      nanoparticles were prepared for thermal energy storage. The influences of Al2O3
      nanoparticles on morphology and thermal performances of the form-stable PCCFMs
      were investigated by scanning electron microscopy (SEM), differential scanning
      calorimetry (DSC), and measurement of melting and freezing times, respectively.
      The results showed that there was no apparent leakage trace from the SEM
      observation. The DSC analysis indicated that the addition of Al2O3 nanoparticles
      had no significant effect on phase transition temperatures and enthalpies of the
      CA-PA-SA/PAN/Al2O3 form-stable PCCFMs. The melting peak temperatures and melting
      enthalpies of form-stable PCCFMs were about 25  degrees C and 131-139 kJ/kg,
      respectively. The melting and freezing times of the CA-PA-SA/PAN/Al2O310 form
      stable PCCFMs were shortened by approximately 21% and 23%, respectively, compared
      with those of the CA-PA-SA/PAN form-stable PCCFMs due to the addition of Al2O3
      nanoparticles acting as heat transfer fillers.

PMID- 30235876
TI  - Neuroprotective Effects of Radix Scrophulariae on Cerebral Ischemia and
      Reperfusion Injury via MAPK Pathways.
AB  - Ischemic stroke is a clinically common cerebrovascular disease whose main risks
      include necrosis, apoptosis and cerebral infarction, all caused by cerebral
      ischemia and reperfusion (I/R). Ischemia and reperfusion-induced injury or
      apoptosis inhibition in human brain tissue may exert an irreplaceable protective
      effect on ischemic nerves. This process has particular significance for the
      treatment of stroke patients. However, the development of neuroprotective drugs
      remains challenging. Radix Scrophulariae, traditionally considered a valuable
      medicine, has been discovered to have neuroprotective effects. To explore the
      neuroprotective effects of an aqueous extract of Radix Scrophulariae (RSAE) on
      cerebral ischemia/reperfusion and their underlying mechanisms, oxygen-glucose
      deprivation and reperfusion (OGD/R)-induced PC12 cells were used, and a middle
      cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. In
      vitro results showed that 12.5 MUg/mL RSAE markedly improved cell viability;
      inhibited LDH leakage; increased SOD, GSH-Px and CAT enzyme activity; stabilized
      the mitochondrial membrane potential; and reduced OGD-induced cell injury and
      apoptosis. Additionally, in vivo results preliminarily suggested that in MCAO/R
      model mice, RSAE treatments attenuated infarct volume; reduced brain water
      content and nitric oxide (NO) and malondialdehyde (MDA) concentrations; inhibited
      I/R-induced neurological deficits; reduced the levels of lactate dehydrogenase
      (LDH) leakage release; improved antioxidant capacity by upregulating SOD, GSH-Px
      and CAT enzyme activity; and reduced neuronal apoptosis, necrosis and loss of
      neurons. Moreover, it was found that RSAE upregulated the expression of Bcl-2 and
      downregulated the expression of Bax. In addition, the phosphorylation levels of
      MAPK signal pathways were elucidated via western blot analysis and
      immunohistochemical evaluation. In summary, this study investigated the
      neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R
      injury in mice. Radix Scrophulariae has been previously identified as a potential
      neuroprotective natural plant. Hence, our results may offer insight into
      discovering new active compounds or drugs for the treatment of ischemic stroke.
      Many new natural active chemicals in this extract may be discovered by chemical
      separation and identification and may provide new insights into therapeutic
      targets in stroke patients.

PMID- 30235877
TI  - Increased Expression of Maturation Promoting Factor Components Speeds Up Meiosis
      in Oocytes from Aged Females.
AB  - The rate of chromosome segregation errors that emerge during meiosis I in the
      mammalian female germ line are known to increase with maternal age; however,
      little is known about the underlying molecular mechanism. The objective of this
      study was to analyze meiotic progression of mouse oocytes in relation to maternal
      age. Using the mouse as a model system, we analyzed the timing of nuclear
      envelope breakdown and the morphology of the nuclear lamina of oocytes obtained
      from young (2 months old) and aged females (12 months old). Oocytes obtained from
      older females display a significantly faster progression through meiosis I
      compared to the ones obtained from younger females. Furthermore, in oocytes from
      aged females, lamin A/C structures exhibit rapid phosphorylation and
      dissociation. Additionally, we also found an increased abundance of MPF
      components and increased translation of factors controlling translational
      activity in the oocytes of aged females. In conclusion, the elevated MPF activity
      observed in aged female oocytes affects precocious meiotic processes that can
      multifactorially contribute to chromosomal errors in meiosis I.

PMID- 30235879
TI  - Cardiac Magnetic Resonance Imaging (MRI) Findings in Arrhythmogenic Right
      Ventricular Dysplasia (ARVD) Compared with Echocardiography.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is an abnormality in the right
      side of the heart that may lead to sudden death. The study aims to compare
      cardiac MRI (magnetic resonance imaging findings) with echocardiography in
      patients with ARVD. For the cross-sectional study, patients with ARVD that were
      diagnosed using Task Force criteria were included, and their cardiac MRI findings
      were evaluated. Additionally, the right ventricle was divided into three levels
      basal, middle, and apical-and each of them was also subdivided into three
      secondary segments. Gadolinium enhancement was evaluated in each segment.
      Overall, 39 patients were studied. Thirty-one patients (81%) were men. The
      average age of female and male patients was 37.8 +/- 4.6 and 32.48 +/- 5.8,
      respectively. The average ejection fraction found was 43 +/- 9.4 and 42.8 +/-
      8.5% by MRI and echocardiography, respectively. Additionally, 46 and 35.8% of the
      patients had hypokinesia in the right ventricle, found based on MRI and
      echocardiography, respectively. The right ventricular aneurysm was found in 20.5
      and 5.1% of patients based on MRI and echocardiography, respectively. The cardiac
      MRI managed to diagnose some cases which echocardiography was not able to detect.
      Thus, MRI plays an important role in presenting diagnostic data for the
      management of patients with ARVD and also making the diagnosis in suspicious
      patients definitive.

PMID- 30235882
TI  - Effect of Tow Size and Interface Interaction on Interfacial Shear Strength
      Determined by Iosipescu (V-Notch) Testing in Epoxy Resin.
AB  - Testing methodologies to accurately quantify interfacial shear strength (IFSS)
      are essential in order to understand fiber-matrix adhesion. While testing methods
      at a microscale (single filament fragmentation test-SFFT) and macroscale (Short
      Beam Shear-SBS) are wide spread, each have their own shortcomings. The Iosipescu
      (V-notch) tow test offers a mesoscale bridge between the microscale and
      macroscale whilst providing simple, accurate results with minimal time
      investment. However, the lack of investigations exploring testing variables has
      limited the application of Iosipescu testing to only a handful of studies. This
      paper assesses the effect of carbon fiber tow size within the Iosipescu tow test
      for epoxy resin. Tow sizes of 3, 6, and 9 k are eminently suitable, while more
      caution must be shown when examining 12, and 15 k tows. In this work, tows at 18
      and 24 k demonstrated failure modes not derived from interfacial failure, but
      poor fiber wetting. A catalogue of common fracture geometries is discussed as a
      function of performance for the benefit of future researchers. Finally, a
      comparison of commercial (T300), amine (T300-Amine), and ethyl ester (T300-Ester)
      surface modified carbon fibers was conducted. The outcomes of this study showed
      that the Iosipescu tow test is inherently less sensitive in distinguishing
      between similar IFSS but provides a more 'real world' image of the carbon fiber
      epoxy interface in a composite material.

PMID- 30235881
TI  - Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic
      Acid-Targeted Cancer Therapy.
AB  - We present here the development of multifunctional doxorubicin (DOX)-conjugated
      poly(amidoamine) (PAMAM) dendrimers as a unique platform for pH-responsive drug
      release and targeted chemotherapy of cancer cells. In this work, we covalently
      conjugated DOX onto the periphery of partially acetylated and folic acid (FA)
      modified generation 5 (G5) PAMAM dendrimers through a pH-sensitive cis-aconityl
      linkage to form the G5.NHAc-FA-DOX conjugates. The formed dendrimer conjugates
      were well characterized using different methods. We show that DOX release from
      the G5.NHAc-FA-DOX conjugates follows an acid-triggered manner with a higher
      release rate under an acidic pH condition (pH = 5 or 6, close to the acidic pH of
      tumor microenvironment) than under a physiological pH condition. Both in vitro
      cytotoxicity evaluation and cell morphological observation demonstrate that the
      therapeutic activity of dendrimer-DOX conjugates against cancer cells is
      absolutely related to the DOX drug released. More importantly, the FA conjugation
      onto the dendrimers allowed a specific targeting to cancer cells overexpressing
      FA receptors (FAR), and allowed targeted inhibition of cancer cells. The
      developed G5.NHAc-FA-DOX conjugates may be used as a promising nanodevice for
      targeted cancer chemotherapy.

PMID- 30235880
TI  - Human Milk Casein and Whey Protein and Infant Body Composition over the First 12
      Months of Lactation.
AB  - Human milk (HM) influences infant feeding patterns and body composition (BC).
      This small proof-of concept longitudinal study investigated relationships between
      infant/maternal BC and HM casein, whey and total protein during the first 12
      months of lactation. BC of breastfeeding dyads (n = 20) was measured at 2 (n =
      15), 5 (n = 20), 9 (n = 19), and/or 12 (n = 18) months postpartum with ultrasound
      skinfolds (infants) and bioimpedance spectroscopy (infants/mothers). Proteins
      concentrations and 24-h milk intake were measured and calculated daily intakes
      (CDI) determined. Higher maternal weight, body mass index, fat-free mass, fat
      free mass index, and fat mass index were associated with higher concentration of
      whey protein (p <= 0.034, n = 20). There were no associations between infant BC
      and concentrations of all proteins, and CDI of whey and total protein. Higher CDI
      of casein were associated with lower infant fat-free mass (p = 0.003, n = 18) and
      higher fat mass (p < 0.001), fat mass index (p = 0.001, n = 18), and % fat mass
      (p < 0.001, n = 18) measured with ultrasound skinfolds. These results show a
      differential effect of HM casein on development of infant BC during the first
      year of life, suggesting that there is a potential to improve outcome for the
      infant through interventions, such as continuation of breastfeeding during the
      first 12 months of life and beyond, which may facilitate favourable developmental
      programming that could reduce risk of non-communicable diseases later in life.

PMID- 30235883
TI  - Self-Diagnosis of Localization Status for Autonomous Mobile Robots.
AB  - It is essential to provide reliable localization results to allow mobile robots
      to navigate autonomously. Even though many state-of-the-art localization schemes
      have so far shown satisfactory performance in various environments, localization
      has still been difficult under specific conditions, such as extreme environmental
      changes. Since many robots cannot diagnose for themselves whether the
      localization results are reliable, there can be serious autonomous navigation
      problems. To solve this problem, this study proposes a self-diagnosis scheme for
      the localization status. In this study, two indicators are empirically defined
      for the self-diagnosis of localization status. Each indicator shows significant
      changes when there are difficulties in light detection and ranging (LiDAR) sensor
      based localization. In addition, the classification model of localization status
      is trained through machine learning using the two indicators. A robot can
      diagnose the localization status itself using the proposed classification model.
      To verify the usefulness of the proposed method, we carried out localization
      experiments in real environments. The proposed classification model successfully
      detected situations where the localization accuracy is significantly degraded due
      to extreme environmental changes.

PMID- 30235878
TI  - Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through
      miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway.
AB  - Guanidinoacetic acid (GAA), an amino acid derivative that is endogenous to animal
      tissues including muscle and nerve, has been reported to enhance muscular
      performance. MicroRNA (miRNA) is a post-transcriptional regulator that plays a
      key role in nutrient-mediated myogenesis. However, the effects of GAA on myogenic
      differentiation and skeletal muscle growth, and the potential regulatory
      mechanisms of miRNA in these processes have not been elucidated. In this study,
      we investigated the effects of GAA on proliferation, differentiation, and growth
      in C2C12 cells and mice. The results showed that GAA markedly inhibited the
      proliferation of myoblasts, along with the down-regulation of cyclin D1 (CCND1)
      and cyclin dependent kinase 4 (CDK4) mRNA expression, and the upregulation of
      cyclin dependent kinase inhibitor 1A (P21) mRNA expression. We also demonstrated
      that GAA treatment stimulated myogenic differentiation 1 (MyoD) and myogenin
      (MyoG) mRNA expression, resulting in an increase in the myotube fusion rate.
      Meanwhile, GAA supplementation promoted myotube growth through increase in total
      myosin heavy chain (MyHC) protein level, myotubes thickness and gastrocnemius
      muscle cross-sectional area. Furthermore, small RNA sequencing revealed that a
      total of eight miRNAs, including miR-133a-3p and miR-1a-3p cluster, showed
      differential expression after GAA supplementation. To further study the function
      of miR-133a-3p and miR-1a-3p in GAA-induced skeletal muscle growth, we
      transfected miR-133a-3p and miR-1a-3p mimics into myotube, which also induced
      muscle growth. Through bioinformatics and a dual-luciferase reporter system, the
      target genes of miR-133a-3p and miR-1a-3p were determined. These two miRNAs were
      shown to modulate the Akt/mTOR/S6K signaling pathway by restraining target gene
      expression. Taken together, these findings suggest that GAA supplementation can
      promote myoblast differentiation and skeletal muscle growth through miR-133a-3p-
      and miR-1a-3p-induced activation of the AKT/mTOR/S6K signaling pathway.

PMID- 30235885
TI  - Transfer Learning for Soil Spectroscopy Based on Convolutional Neural Networks
      and Its Application in Soil Clay Content Mapping Using Hyperspectral Imagery.
AB  - Soil spectra are often measured in the laboratory, and there is an increasing
      number of large-scale soil spectral libraries establishing across the world.
      However, calibration models developed from soil libraries are difficult to apply
      to spectral data acquired from the field or space. Transfer learning has the
      potential to bridge the gap and make the calibration model transferrable from one
      sensor to another. The objective of this study is to explore the potential of
      transfer learning for soil spectroscopy and its performance on soil clay content
      estimation using hyperspectral data. First, a one-dimensional convolutional
      neural network (1D-CNN) is used on Land Use/Land Cover Area Frame Survey (LUCAS)
      mineral soils. To evaluate whether the pre-trained 1D-CNN model was
      transferrable, LUCAS organic soils were used to fine-tune and validate the model.
      The fine-tuned model achieved a good accuracy (coefficient of determination (R2)
      = 0.756, root-mean-square error (RMSE)= 7.07 and ratio of percent deviation (RPD)
      = 2.26) for the estimation of clay content. Spectral index, as suggested as a
      simple transferrable feature, was also explored on LUCAS data, but did not
      performed well on the estimation of clay content. Then, the pre-trained 1D-CNN
      model was further fine-tuned by field samples collect in the study area with
      spectra extracted from HyMap imagery, achieved an accuracy of R2 = 0.601, RMSE =
      8.62 and RPD = 1.54. Finally, the soil clay map was generated with the fine-tuned
      1D-CNN model and hyperspectral data.

PMID- 30235886
TI  - Coffee Consumption and the Risk of Depression in a Middle-Aged Cohort: The SUN
      Project.
AB  - Coffee is one of the most widely consumed drinks around the world, while
      depression is considered the major contributor to the overall global burden of
      disease. However, the investigation on coffee consumption and depression is
      limited and results may be confounded by the overall dietary pattern. We assessed
      the relationship between coffee intake and the risk of depression, controlling
      for adherence to the Mediterranean diet. We studied 14,413 university graduates
      of the 'Seguimiento Universidad de Navarra' (SUN) cohort, initially free of
      depression. We evaluated coffee consumption using a validated food-frequency
      questionnaire (FFQ). Incident depression cases were adjudicated only if the
      participant met two criteria simultaneously: (a) validated physician-diagnosed
      depression together with (b) new onset of habitual antidepressant use. Both
      criteria were needed; participants meeting only one of them were not classified
      as cases. Participants who drank at least four cups of coffee per day showed a
      significantly lower risk of depression than participants who drank less than one
      cup of coffee per day (HR: 0.37 (95% CI 0.15-0.95)). However, overall, we did not
      observe an inverse linear dose-response association between coffee consumption
      and the incidence of depression (p for trend = 0.22).

PMID- 30235884
TI  - Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens.
AB  - Fungal infections, such as candidiasis caused by Candida, pose a problem of
      growing medical concern. In developed countries, the incidence of Candida
      infections is increasing due to the higher survival of susceptible populations,
      such as immunocompromised patients or the elderly. Existing treatment options are
      limited to few antifungal drug families with efficacies that vary depending on
      the infecting species. In this context, the emergence and spread of resistant
      Candida isolates are being increasingly reported. Understanding how resistance
      can evolve within naturally susceptible species is key to developing novel, more
      effective treatment strategies. However, in contrast to the situation of
      antibiotic resistance in bacteria, few studies have focused on the evolutionary
      mechanisms leading to drug resistance in fungal species. In this review, we will
      survey and discuss current knowledge on the genetic bases of resistance to
      antifungal drugs in Candida opportunistic pathogens. We will do so from an
      evolutionary genomics perspective, focusing on the possible evolutionary paths
      that may lead to the emergence and selection of the resistant phenotype. Finally,
      we will discuss the potential of future studies enabled by current developments
      in sequencing technologies, in vitro evolution approaches, and the analysis of
      serial clinical isolates.

PMID- 30235887
TI  - Fuzzy Group Consensus Decision Making and Its Use in Selecting Energy-Saving and
      Low-carbon Technology Schemes in Star Hotels.
AB  - Energy-saving and low-carbon technologies play important roles in reducing
      environmental risk and developing green tourism. An energy-saving and low-carbon
      technology scheme selection may often involve multiple criteria and sub-criteria
      as well as multiple stakeholders or decision makers, and thus can be structured
      as a hierarchical multi-criteria group decision making problem. This paper
      proposes a framework to solve group consensus decision making problems, where
      decision makers' preferences between the alternatives considered with respective
      to each criterion are elicited by the paired comparison method, and expressed as
      triangular fuzzy preference relations (TFPRs). The paper first simplifies the
      existing computation formulas used to determine triangular fuzzy weights of
      TFPRs. A consistency index is then devised to measure the inconsistency degree of
      a TFPR and is used to check acceptable consistency of TFPRs. By introducing a
      possibility degree formula of comparing any two triangular fuzzy weights, an
      index is defined to measure the consensus level between an individual ranking
      order and the group ranking order for all alternatives. A consensus model is
      developed in detail for solving group decision making problems with TFPRs. A case
      study of selecting energy-saving and low-carbon technology schemes in star hotels
      is provided to illustrate how to apply the proposed group decision making
      consensus model in practice.

PMID- 30235888
TI  - Beeswax by-Products Efficiently Counteract the Oxidative Damage Induced by an
      Oxidant Agent in Human Dermal Fibroblasts.
AB  - The antioxidant capacity and the phytochemical composition of two by-products
      from beeswax recycling processes were recently investigated. The aim of the
      present work was to evaluate the efficacy of one of these by-products, MUD1,
      against the oxidative stress induced by 2,2'-azobis(2-amidinopropane)
      dihydrochloride (AAPH) in human dermal fibroblast (HDF) cells. After a
      preliminary viability assay, the protective effect of MUD1 was investigated
      through the measurement of apoptosis level, the reactive oxygen species (ROS) and
      nitrite (NO2-) production, the level of protein and lipid biomarkers (carbonyl
      groups, total glutathione and thiobarbituric acid-reactive substance) of
      oxidative damage, and the measurement of antioxidant enzymes activities
      (glutatione peroxidase, glutathione reductase, glutathione transferase,
      superoxide dismutase and catalase). The obtained results showed that MUD1 exerted
      protective effects on HDF, increasing cell viability and counteracted the
      oxidative stress promoted by AAPH-treatment, and improved mitochondria
      functionality and wound healing capacities. This work shows the antioxidant
      effects exerted by beeswax by-products, demonstrating for the first time their
      potential against oxidative stress in human dermal fibroblast cells; however,
      further research will be necessary to evaluate their potentiality for human
      health by more deeply in vitro and in vivo studies.

PMID- 30235889
TI  - Characterization of alpha-Glucosidase Inhibitors from Clinacanthus nutans Lindau
      Leaves by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular
      Docking Simulation.
AB  - BACKGROUND: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub
      traditionally consumed to treat various diseases including diabetes in Malaysia.
      This study was designed to evaluate the alpha-glucosidase inhibitory activity of
      C. nutans leaves extracts, and to identify the metabolites responsible for the
      bioactivity. METHODS: Crude extract obtained from the dried leaves using 80%
      methanolic solution was further partitioned using different polarity solvents.
      The resultant extracts were investigated for their alpha-glucosidase inhibitory
      potential followed by metabolites profiling using the gas chromatography tandem
      with mass spectrometry (GC-MS). RESULTS: Multivariate data analysis was developed
      by correlating the bioactivity, and GC-MS data generated a suitable partial least
      square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid,
      phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene,
      pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol
      monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular
      docking was carried out using the crystal structure Saccharomyces cerevisiae
      isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein
      were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411,
      and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding.
      CONCLUSION: The study provides informative data on the potential alpha
      glucosidase inhibitors identified in C. nutans leaves, indicating the plant's
      therapeutic effect to manage hyperglycemia.

PMID- 30235890
TI  - BDCA1+CD14+ Immunosuppressive Cells in Cancer, a Potential Target?
AB  - Dendritic cell (DC) vaccines show promising effects in cancer immunotherapy.
      However, their efficacy is affected by a number of factors, including (1) the
      quality of the DC vaccine and (2) tumor immune evasion. The recently
      characterized BDCA1+CD14+ immunosuppressive cells combine both aspects; their
      presence in DC vaccines may directly hamper vaccine efficacy, whereas, in
      patients, BDCA1+CD14+ cells may suppress the induced immune response in an
      antigen-specific manner systemically and at the tumor site. We hypothesize that
      BDCA1+CD14+ cells are present in a broad spectrum of cancers and demand further
      investigation to reveal treatment opportunities and/or improvement for DC
      vaccines. In this review, we summarize the findings on BDCA1+CD14+ cells in solid
      cancers. In addition, we evaluate the presence of BDCA1+CD14+ cells in leukemic
      cancers. Preliminary results suggest that the presence of BDCA1+CD14+ cells
      correlates with clinical features of acute and chronic myeloid leukemia. Future
      research focusing on the differentiation from monocytes towards BDCA1+CD14+ cells
      could reveal more about their cell biology and clinical significance. Targeting
      these cells in cancer patients may improve the outcome of cancer immunotherapy.

PMID- 30235892
TI  - Andrographolide Protects PC12 Cells Against beta-Amyloid-Induced Autophagy
      Associated Cell Death Through Activation of the Nrf2-Mediated p62 Signaling
      Pathway.
AB  - Recent studies mentioned that Andrographolide (Andro), the main bioactive
      component of traditional Chinese medicine Andrographis paniculata, may be a
      potential natural product for treating Alzheimer's disease, but the underlining
      mechanism remains to be discovered. In this study, we investigated whether Andro
      regulates the nuclear factor E2-related factor 2 (Nrf2)/Sequestosome 1 (p62)
      signaling pathway and activates autophagy to protect neuronal PC12 cells from the
      toxicity of the beta-amyloid (Abeta) peptide. Our results revealed that Andro
      protected and rescued PC12 cells from Abeta1-42-induced cell death and restored
      abnormal changes in nuclear morphology, lactate dehydrogenase, malondialdehyde,
      intracellular reactive oxygen species, and mitochondrial membrane potential. RT
      PCR and Western blotting analysis demonstrated that Andro activated autophagy
      related genes and proteins (Beclin-1 and LC3); meanwhile, it also augmented the
      Nrf2 and p62 expression in mRNA and protein levels, and reduced p-tau and p21
      protein expression in Abeta1-42-stimulated cells. Then, further study showed that
      the pre-transfection of cells with Nrf2 small interfering RNA (siRNA) resulted in
      the downregulation of p62, Beclin-1, and LC3 proteins expression, as well as the
      upregulation of p21. Furthermore, the pre-transfection of cells with p62 siRNA
      didn't block the Nrf2 protein expression, accompanying with an elevated p21.
      Taken together, these results showed that Andro significantly ameliorated cell
      death due to Abeta1-42 insult through the activation of autophagy and the Nrf2
      mediated p62 signaling pathway.

PMID- 30235894
TI  - Path Smoothing Techniques in Robot Navigation: State-of-the-Art, Current and
      Future Challenges.
AB  - Robot navigation is an indispensable component of any mobile service robot. Many
      path planning algorithms generate a path which has many sharp or angular turns.
      Such paths are not fit for mobile robot as it has to slow down at these sharp
      turns. These robots could be carrying delicate, dangerous, or precious items and
      executing these sharp turns may not be feasible kinematically. On the contrary,
      smooth trajectories are often desired for robot motion and must be generated
      while considering the static and dynamic obstacles and other constraints like
      feasible curvature, robot and lane dimensions, and speed. The aim of this paper
      is to succinctly summarize and review the path smoothing techniques in robot
      navigation and discuss the challenges and future trends. Both autonomous mobile
      robots and autonomous vehicles (outdoor robots or self-driving cars) are
      discussed. The state-of-the-art algorithms are broadly classified into different
      categories and each approach is introduced briefly with necessary background,
      merits, and drawbacks. Finally, the paper discusses the current and future
      challenges in optimal trajectory generation and smoothing research.

PMID- 30235893
TI  - Low Protein Intake Is Associated with Frailty in Older Adults: A Systematic
      Review and Meta-Analysis of Observational Studies.
AB  - (1) Background: Several factors have been suggested to be associated with the
      physiopathology of frailty in older adults, and nutrition (especially protein
      intake) has been attributed fundamental importance in this context. The objective
      of this study was to conduct a systematic review and meta-analysis to investigate
      the relationship between protein intake and frailty status in older adults. (2)
      Methods: A search of scientific studies was conducted in the main databases
      (Medline, Scopus, Cochrane library), and in the reference lists of selected
      articles. The search terms included synonyms and Medical Subject Headings and
      involved the use of Boolean operators which allowed the combination of words and
      search terms. Observational studies-cross-sectional and longitudinal-that met the
      eligibility criteria were included in the review. Article selection and data
      extraction were performed by two independent reviewers. Meta-analyses with random
      effects were performed. Publication bias was measured using the Strengthening the
      Reporting of Observational Studies in Epidemiology instrument. (3) Results: In
      the final sample, 10 articles, seven cross-sectional and three longitudinal, were
      included in the present study. Overall, studies investigated a total of 50,284
      older adults from three different continents between 2006 and 2018. Four cross
      sectional studies were included in the meta-analyses. The results demonstrated
      that a high protein intake was negatively associated with frailty status in older
      adults (odds ratio: 0.67, confidence interval = 0.56 to 0.82, p = 0.0001). (4)
      Conclusions: Our findings suggest that a high consumption of dietary protein is
      inversely associated with frailty in older adults.

PMID- 30235895
TI  - Vitamin B12 Deficiency Induces Imbalance in Melanocytes Homeostasis-A Cellular
      Basis of Hypocobalaminemia Pigmentary Manifestations.
AB  - Vitamin B12 deficiency causes significant changes in cellular metabolism leading
      to various clinical symptoms, such as hematological, psychiatric, and
      neurological disorders. We hypothesize that skin pigmentation disorders may be a
      diagnostically important manifestation of vitamin B12 deficiency, however the
      cellular and molecular mechanisms underlying these effects remain unknown. The
      aim of this study was to examine the effect of vitamin B12 deficiency on
      melanocytes homeostasis. Hypocobalaminemia in vitro model was developed by
      treating epidermal melanocytes with synthesized vitamin B12 antagonist
      hydroxycobalamin(c-lactam). The cells were examined using immunoenzymatic,
      spectrophotometric, and fluorimetric assays as well as image cytometry.
      Significant melanogenesis stimulation-the increase of relative melanin content
      and tyrosinase activity up to 131% and 135%, respectively-has been indicated.
      Cobalamin-deficient cells displayed the elevation (by 120%) in reactive oxygen
      species level. Moreover, the redox status imbalance was stated. The study
      provided a scientific evidence for melanocytes homeostasis disturbance under
      hypocobalaminemia, thus indicating a significant element of the hyperpigmentation
      mechanism due to vitamin B12 deficiency. Furthermore, the implication between
      pigmentary and hematological and/or neuropsychiatric symptoms in cobalamin
      deficient patients may be an important issue.

PMID- 30235897
TI  - Reliability and Maintenance Analysis of Unmanned Aerial Vehicles.
AB  - This paper focuses on the development of a new logistic approach based on
      reliability and maintenance assessment, with the final aim of establishing a more
      efficient interval for the maintenance activities for Unmanned Aerial Vehicles
      (UAV). In the first part, we develop an architectural philosophy to obtain a more
      detailed reliability evaluation; then, we study the intrinsic reliability at the
      design stage in order to avoid severe critical issues in the UAV. In the second
      part, we compare different maintenance philosophies for UAVs and develop the
      concepts of preventive and corrective maintenance that consider the system
      subjected (until real "hard failure") to partial performance degradation ("soft
      failure"). Finally, by evaluation of the uncertainty through the confidence
      interval, we determine the new soft failure limits, taking into account the
      general knowledge of the systems and subsystems in order to guarantee the proper
      preventive maintenance interval.

PMID- 30235891
TI  - Aloe Genus Plants: From Farm to Food Applications and Phytopharmacotherapy.
AB  - Aloe genus plants, distributed in Old World, are widely known and have been used
      for centuries as topical and oral therapeutic agents due to their health, beauty,
      medicinal, and skin care properties. Among the well-investigated Aloe species are
      A. arborescens, A. barbadensis, A. ferox, and A. vera. Today, they account among
      the most economically important medicinal plants and are commonly used in primary
      health treatment, where they play a pivotal role in the treatment of various
      types of diseases via the modulation of biochemical and molecular pathways,
      besides being a rich source of valuable phytochemicals. In the present review, we
      summarized the recent advances in botany, phytochemical composition,
      ethnobotanical uses, food preservation, and the preclinical and clinical efficacy
      of Aloe plants. These data will be helpful to provide future directions for the
      industrial and medicinal use of Aloe plants.

PMID- 30235896
TI  - The Feasibility and Acceptability of The Girls Peer Activity (G-PACT) Peer-led
      Mentoring Intervention.
AB  - Enjoyment of physical activity (PA) is positively correlated with PA engagement.
      The inclusion of peers has been found to increase the likelihood of PA enjoyment
      in youth. Peer-led strategies, incorporating peer networks in the intervention
      delivery, is relatively underused and consequently understudied in school-based
      PA interventions. The purpose of this investigation was to evaluate the
      feasibility and acceptability of the novel Girls Peer Activity (G-PACT) peer-led
      mentoring intervention. Two-hundred and forty-nine Year 9 adolescent girls (13-14
      years old) from three mixed-sex secondary schools located in West Lancashire,
      North-West England were invited to participate in the G-PACT project. The study
      employed a novel approach by using a three-tier model, including (Tier 1) Mentors
      (undergraduate students), (Tier 2) Leaders (Year 9 girls selected by teachers),
      and (Tier 3) Peers (whole Year 9 cohort). Mentors delivered a series of
      educational and leadership training to the Leaders in each respective school who
      then disseminated this information to their Peers and encouraged them to engage
      in more physical activities. Eight focus groups were conducted with Leaders (n =
      40), 28 focus groups with Peers (n = 185), two focus groups with Mentors (n = 6),
      and three interviews with teachers (n = 4). Thematic analysis was used to analyze
      the pooled data and identify the key themes. The study found that the G-PACT
      intervention was feasible and acceptable for adolescent PA Leaders and their
      Mentors. The relationship between Leaders and their Peers required refinement to
      improve the communication processes to increase Peer engagement in the G-PACT
      project.

PMID- 30235898
TI  - Quantitative Assessment of Relationship between Population Exposure to PM2.5 and
      Socio-Economic Factors at Multiple Spatial Scales over Mainland China.
AB  - Analyzing the association between fine particulate matter (PM2.5) pollution and
      socio-economic factors has become a major concern in public health. Since
      traditional analysis methods (such as correlation analysis and geographically
      weighted regression) cannot provide a full assessment of this relationship, the
      quantile regression method was applied to overcome such a limitation at different
      spatial scales in this study. The results indicated that merely 3% of the
      population and 2% of the Gross Domestic Product (GDP) occurred under an annually
      mean value of 35 MUg/m3 in mainland China, and the highest population exposure to
      PM2.5 was located in a lesser-known city named Dazhou in 2014. The analysis
      results at three spatial scales (grid-level, county-level, and city-level)
      demonstrated that the grid-level was the optimal spatial scale for analysis of
      socio-economic effects on exposure due to its tiny uncertainty, and the
      population exposure to PM2.5 was positively related to GDP. An apparent upward
      trend of population exposure to PM2.5 emerged at the 80th percentile GDP. For a
      10 thousand yuan rise in GDP, population exposure to PM2.5 increases by 1.05
      person/km2 at the 80th percentile, and 1.88 person/km2 at the 95th percentile,
      respectively.

PMID- 30235899
TI  - The GIS2 Gene Is Repressed by a Zinc-Regulated Bicistronic RNA in Saccharomyces
      cerevisiae.
AB  - Zinc homeostasis is essential for all organisms. The Zap1 transcriptional
      activator regulates these processes in the yeast Saccharomyces cerevisiae. During
      zinc deficiency, Zap1 increases expression of zinc transporters and proteins
      involved in adapting to the stress of zinc deficiency. Transcriptional activation
      by Zap1 can also repress expression of some genes, e.g., RTC4. In zinc-replete
      cells, RTC4 mRNA is produced with a short transcript leader that is efficiently
      translated. During deficiency, Zap1-dependent expression of an RNA with a longer
      transcript leader represses the RTC4 promoter. This long leader transcript (LLT)
      is not translated due to the presence of small open reading frames upstream of
      the RTC4 coding region. In this study, we show that the RTC4 LLT RNA also plays a
      second function, i.e., repression of the adjacent GIS2 gene. In generating the
      LLT transcript, RNA polymerase II transcribes RTC4 through the GIS2 promoter.
      Production of the LLT RNA correlates with the decreased expression of GIS2 mRNA
      and mutations that prevent synthesis of the LLT RNA or terminate it before the
      GIS2 promoter renders GIS2 mRNA expression and Gis2 protein accumulation
      constitutive. Thus, we have discovered an unusual regulatory mechanism that uses
      a bicistronic RNA to control two genes simultaneously.

PMID- 30235900
TI  - Optimization of Transesterification Reactions with CLEA-Immobilized Feruloyl
      Esterases from Thermothelomyces thermophila and Talaromyces wortmannii.
AB  - Feruloyl esterases (FAEs, E.C. 3.1.1.73) are biotechnologically important enzymes
      with several applications in ferulic acid production from biomass, but also in
      synthesis of hydroxycinnamic acid derivatives. The use of such biocatalysts in
      commercial processes can become feasible by their immobilization, providing the
      advantages of isolation and recycling. In this work, eight feruloyl esterases,
      immobilized in cross-linked enzyme aggregates (CLEAs) were tested in regard to
      their transesterification performance, towards the production of prenyl ferulate
      (PFA) and arabinose ferulate (AFA). After solvent screening, comparison with the
      activity of respective soluble enzymes, and operational stability tests, FAE125
      was selected as the most promising biocatalyst. A central composite design
      revealed the optimum conditions for each transesterification product, in terms of
      water content, time, and substrate ratio for both products, and temperature and
      enzyme load additionally for prenyl ferulate. The optimum product yields obtained
      were 83.7% for PFA and 58.1% for AFA. FAE125 CLEAs are stable in the optimum
      conditions of transesterification reactions, maintaining 70% residual activity
      after five consecutive reactions. Overall, FAE125 CLEAs seem to be able to
      perform as a robust biocatalyst, offering satisfactory yields and stability, and
      thus showing significant potential for industrial applications.

PMID- 30235901
TI  - Deep Learning-Based Caution Area Traffic Prediction with Automatic Identification
      System Sensor Data.
AB  - In a crowded harbor water area, it is a major concern to control ship traffic for
      assuring safety and maximizing the efficiency of port operations. Vessel Traffic
      Service (VTS) operators pay much attention to caution areas like ship route
      intersections or traffic congestion area in which there are some risks of ship
      collision. They want to control the traffic of the caution area at a proper level
      to lessen risk. Inertial ship movement makes swift changes in direction and speed
      difficult. It is hence important to predict future traffic of the caution area
      earlier on so as to get enough time for control actions on ship movements. In the
      harbor area, VTS stations collect a large volume of Automatic Identification
      Service (AIS) sensor data, which contain information about ship movement and ship
      attributes. This paper proposes a new deep neural network model called Ship
      Traffic Extraction Network (STENet) to predict the medium-term traffic and long
      term traffic of the caution area. The STENet model is trained with AIS sensor
      data. The STENet model is organized into a hierarchical architecture in which the
      outputs of the movement and contextual feature extraction modules are
      concatenated and fed into a prediction module. The movement module extracts the
      features of overall ship movements with a convolutional neural network. The
      contextual modules consist of five separated fully-connected neural networks,
      each of which receives an associated attribute. The separation of feature
      extraction modules at the front phase helps extract the effective features by
      preventing unrelated attributes from crosstalking. To evaluate the performance of
      the proposed model, the developed model is applied to a real AIS sensor dataset,
      which has been collected over two years at a Korean port called Yeosu. In the
      experiments, four methods have been compared including two new methods: STENet
      and VGGNet-based models. For the real AIS sensor dataset, the proposed model has
      shown 50.65% relative performance improvement on average for the medium-term
      predictions and 57.65% improvement on average for the long-term predictions over
      the benchmark method, i.e., the SVR-based method.

PMID- 30235905
TI  - The origin and fate of spermatophores in the viviparous teleost Cymatogaster
      aggregata (Perciformes: Embiotocidae).
AB  - The sperm of the shiner surfperch are packaged into high density aggregations
      which are introduced into the female genital tract at insemination. Germ cell
      differentiation occurs within cysts formed by nongerminal Sertoli cells. In late
      spermiogenesis, spermatozoa within the cysts come to lie parallel to each other
      and become more densely packed. These sperm packets (spermatophores), containing
      approximately 600 spermatozoa, then are released into the efferent sperm ducts.
      The exact nature of the spermatophore binding material is not known, but a major
      component is proteinaceous and is synthesized in the rough endoplasmic reticulum
      of the efferent sperm duct epithelial cells. The mechanism by which the
      spermatophores pass from cysts into ducts is not clear. It appears that whereas
      many Sertoli cells degenerate causing the cyst wall to break down, many Sertoli
      cells do not degenerate, but rather assume the configuration of columnar duct
      cells. The spermatophores remain intact within the testicular ducts, but rapidly
      dissolve within the female ducts in response to increased pH.

PMID- 30235903
TI  - Personal Involvement Moderates Message Framing Effects on Food Safety Education
      among Medical University Students in Chongqing, China.
AB  - OBJECTIVE: This study explored whether the efficacy of food safety education
      interventions can be increased by message framing among medical university
      students, and demonstrated the role of personal involvement within the message
      recipient in moderating framed effects. METHODS: A cross-sectional study of food
      safety message framing was conducted among medical university students (randomly
      selected 1353 participants). An online self-administered questionnaire was used
      to collect information. Wilcoxon rank-sum test and Ordered multivariate logistic
      regression were utilised in the data analyses. RESULTS: The present study showed
      significant differences in acceptance between the gain- and loss-framed groups (p
      < 0.001). Participants with higher personal involvement had higher acceptance
      than those with low personal involvement in gain- and loss-framed message models
      (p < 0.001). The acceptance of participants who were concerned about their health
      condition was higher than those who were neutral regarding their health condition
      (p < 0.001) and participants who suffered a food safety incident had higher
      acceptance than those who did not (p < 0.05). CONCLUSIONS: This study portrayed
      the selection preference of message framing on food safety education among
      medical university students in southwest China. Participants exposed to loss
      framed messages had higher message acceptance than those exposed to gain-framed
      messages. Personal involvement may affect the food safety message framing. Public
      health advocates and professionals can use framed messages as a strategy to
      enhance intervention efficacy in the process of food safety education.

PMID- 30235902
TI  - Instrumentation for Vibrational Circular Dichroism Spectroscopy: Method
      Comparison and Newer Developments.
AB  - Vibrational circular dichroism (VCD) is a widely used standard method for
      determination of absolute stereochemistry, and somewhat less so for biomolecule
      characterization and following dynamic processes. Over the last few decades,
      different VCD instrument designs have developed for various purposes, and
      reliable commercial instrumentation is now available. This review will briefly
      survey historical and currently used instrument designs and describe some aspects
      of more recently reported developments. An important factor in applying VCD to
      conformational studies is theoretical modeling of spectra for various structures,
      techniques for which are briefly surveyed.

PMID- 30235906
TI  - Ultrastructural studies on the formation of yolk granules in the statoblast of a
      fresh-water bryozoan, Pectinatella gelatinosa.
AB  - The formation of protein-carbohydrate yolk in the statoblast of a fresh-water
      bryozoan, Pectinatella gelatinosa, was studied by electron microscopy. Two types
      (I and II) of yolk cells were distinguished. The type I yolk cells are
      mononucleate and comprise a large majority of the yolk cells. The type II yolk
      cells are small in number; they become multinucleate by fusion of cells at an
      early stage of vitellogenesis. In both types of yolk cells, electron-dense
      granules (dense bodies) are formed in Golgi or condensing vacuoles, which are
      then called yolk granules. For the formation of yolk granules, the following
      processes are considered: 1. Yolk protein is synthesized in the rough-surfaced
      endoplasmic reticulum (RER) of the yolk cells. 2. The synthesized protein
      condenses in the cisternal space of the RER and is packaged into small oval
      swellings, which are then released from the RER as small vesicles (Golgi
      vesicles, 300-600 A in diameter). 3. The small vesicles fuse with one another to
      form condensing vacuoles, or with pre-existing growing yolk granules. 4. In the
      matrix of the condensing vacuoles or growing yolk granules, electron-dense fibers
      are fabricated and then arranged in a paracrystalline pattern to form the dense
      body. 5. After the dense body reaches its full size, excess membrane is removed
      and eventually the yolk granules come to mature. Toward the end of vitellogenesis
      of the yolk cells, the cytoplasmic organelles are ingested by autophagosomes
      derived from multivesicular bodies and disappear.

PMID- 30235904
TI  - Effects of Progressive Resistance Training on Post-Surgery Incontinence in Men
      with Prostate Cancer.
AB  - We evaluated the efficacy of progressive resistance training of the pelvic floor
      muscle for post-prostatectomy incontinence. In this prospective study, 59
      patients who underwent radical prostatectomy were evaluated preoperatively.
      Continence was sequentially assessed within 2 weeks postoperatively, and an
      exercise regimen was initiated at 6- and 12-weeks. The primary outcome was
      continent status and the secondary outcome was changes in muscle strength and
      endurance after the exercise intervention. Continence was defined as no urine
      loss in a 1h pad test. A total of 59 patients participated in this study. Six
      patients dropped out of the study because of non-compliance and orthopedic
      problems. Of the remaining 53 patients, 31 (58.5%) achieved pad-free continence
      at 12 weeks postoperatively. The patients were divided into two groups based on
      their continence status, and no statistically significant difference was observed
      in age, body mass index, prostate volume, prostate-specific antigen, pathological
      Gleason score sum, and pathological T stage. Meanwhile, preoperative maximal
      urethral closure pressure and change in hip extensor muscle strength and
      endurance during the 12-week exercise program were significantly higher in the
      continent group. In multivariate analysis, change in hip extensor muscle strength
      was the only significant parameter predicting achievement of continence status
      (Odds ratio, 1.039; p = 0.045). The changes in hip extensor muscle strength in
      the current exercise program was an independent predictor of continence status
      after radical prostatectomy. A large-scale prospective study on the relationship
      between extensor muscle strength and urinary incontinence should be explored in
      future.

PMID- 30235907
TI  - The fine structure of the salivary glands in the cockroach Gromphadorhina
      portentosa: Secretion.
AB  - Secretion in the salivary glands of Gromphadorhina portentosa involves three cell
      types: parietal cells, secretory cells, and duct cells. The organization and role
      of the parietal and secretory cells are here considered. Parietal cells have
      numerous mitochondria, indicating an active metabolic role and the subsequent
      production of ATP. Plasma membrane invaginations and intracellular ductules
      containing microvilli appear to function in the absorption of solutes from the
      hemolymph and finely-tapered ductules. Secretory cells contain abundant rough
      endoplasmic reticulum, the three forms (stacked, vesicular, and diffuse) of which
      appear to develop sequentially during maturation. Secretory vesicle formation is
      asynchronous between adjacent secretory cells, and apparently the large vesicles
      often coalesce. The secretory vesicles also show differing degrees of electron
      density, indicating distinct biochemical composition.

PMID- 30235908
TI  - The vasculature of the gills in the aquatic and aestivating lungfish (Protopterus
      aethiopicus).
AB  - Studies were undertaken of the microcirculation and histology of the gill of
      Protopterus aethiopicus as a prerequisite for elucidating the function of the
      gills in a bimodal respiratory system. The lamellae of the gill-bearing arches
      (I, IV, V, VI) resembles the arborescent external gill of the larval amphibian
      rather than the gill of the teleost or selachian. The arterio-arterial system (a
      a) of the gill consists of an afferent artery, a series of large capillaries, and
      an efferent artery on each of the primary, secondary and tertiary lamellae. There
      are no pillar cells and the loose capillaries are covered with a multilayered
      epithelium. While living in water, the minimum distance for gas exchange is of
      the order of 5 MU. An afferent-efferent arterial shunt at the base of each
      primary lamella may be involved in control of lamellar blood flow and the
      resistance of the gill vasculature. The arterio-venous system originates
      primarily from the efferent side of the arterio-arterial system and drains into
      large branchial veins. Numerous contractile cisternae, interposed between
      intercellular channels and veins, presumably function as micropumps that collect
      fluid from intercellular epithelial spaces and inject it into the venous
      circulation. During aestivation, the epithelial layer of the gill lamellae
      becomes thinner. The entire gill vasculature, including the capillaries and
      afferent-efferent shunts on arches IV-VI, are very dilated which presumably
      promotes blood flow through these gill arches to the lungs.

PMID- 30235909
TI  - Time-lapse cinemicrographic analysis of superficial cell behavior during and
      prior to gastrulation in Xenopus laevis.
AB  - Time-lapse cinemicrography was used to show what changes in the number, size,
      shape, arrangement and what movements of apices of superficial cells occur during
      epiboly, extension, convergence and blastopore formation in the blastula or
      gastrula of Xenopus laevis. Epiboly of the animal region occurs by apical
      expansion of superficial cells at a nearly constant rate from the midblastula to
      the midgastrula stage. Egression of deep cells into the superficial layer does
      not occur. Extension of the dorsal marginal zone begins in the late blastula
      stage with the rapid spreading of the apices of cells in this region and this
      continues until the onset of neurulation when rapid shrinkage begins. Extension
      and convergence of the dorsal marginal zone occurs by a rearrangement in which
      individual cells exchange neighbors and by a change in the shape of the cell
      apices. Regional differences in apical expansion are accompanied by differences
      in rate of anticlinal division of superficial cells such that cells in all
      sectors of the animal region and the marginal zone show similar patterns of
      decrease in apparent apical area. Shrinkage of the apices of bottle cells during
      blastopore formation is described. From this and other studies, a model of the
      cellular behavior of epiboly, extension and convergence is constructed and
      several hypotheses as to how these activities might generate the mechanical
      forces of the gastrulation movements are presented.

PMID- 30235910
TI  - The early embryonic mitosis in normal and cooled eggs of the silkworm, Bombyx
      mori.
AB  - Early embryonic mitosis of the silkworm, Bombyx mori, was morphologically studied
      in the normal eggs and in the eggs treated by low temperature (-10 degrees C).
      The first embryonic mitosis is observed in the eggs at 120 to 150 minutes after
      deposition at 26 degrees C. After egg and sperm pronuclei unite, a spindle is
      formed in each of the pronuclei independently. At metaphase and anaphase paternal
      and maternal chromosomes are in separate groups on a spindle (gonomeric) and
      karyogamy takes place at telophase when they reach the poles. The second
      embryonic mitosis is shown in the eggs at 180 to 210 minutes after deposition.
      The division of two nuclei is not synchronous in the silkworm, and the mitosis is
      not gonomeric. In the eggs treated by low temperature, spindle fibers are not
      observed at all at -10 degrees C, and chromosomes, which form two deeply stained
      masses of irregular shape, are seen in the less stained area of spindle shape.
      When the eggs are returned to 26 degrees C, some eggs go into normal gonomeric
      division, while some form two small and compact spindles, which seem to be
      derived from each of the pronuclei. It was observed that these compact spindles
      are able to continue mitosis.

PMID- 30235911
TI  - The ultrastructure of the metathoracic femoral extensors of the cockroach,
      Periplaneta americana.
AB  - The ultrastructure of the femoral extensors of the metathoracic leg of the
      cockroach, Periplaneta americana was studied to determine morphological
      correlations with the known patterns of innervation, physiological properties and
      biochemical properties. Three different types of muscle fibers were described.
      Type 1 consisted of short sarcomeres (mean 3.7 MUm), few mitochondria and sparse
      glycogen-like material; Type 2, short sarcomeres (4.2 MUm), numerous
      mitochondria, large amounts of glycogen; Type 3, long sarcomeres (7.5 MUm),
      numerous mitochondria and large amounts of glycogen. A qualitative examination of
      the sarcoplasmic reticulum (SR) and transverse tubular system (TTS) revealed the
      density of SR and TTS to be greatest in Type 1 and least in Type 3. There were
      obvious correlations between the morphological features and the other known
      characteristics of these muscle fibers. The role of these different muscle fiber
      types in different locomotory behaviors was discussed. In summary, the three
      types of muscle fibers are used in three different behaviors: Type 1, rapid
      walking; Type 2, slow walking; Type 3, postural control.

PMID- 30235912
TI  - The nervous system in planarians: Peripheral and gastrodermal plexuses, pharynx
      innervation, and the relationship between central nervous system structure and
      the acoelomate organization.
AB  - The Champy-Maillet osmium tetroxide-zinc iodide technique and a new method using
      azur B-sodium thioglycolate were used to study the general nervous tissue
      structure in planarians. A subepidermal and a submuscular nerve plexus, partially
      reported by earlier authors, are described, and a gastrodermal plexus is reported
      for the first time in triclads. The possible functions for each one of these
      plexuses are discussed. By the Champy-Maillet method, the innervation within the
      parenchyma appears as an array of numerous single nerve fibers that course
      between the parenchyma cells making apparent synaptic contacts. The pharynx has
      outer and inner nerve nets similar in structure to the submuscular nerve plexus.
      Both nerve nets are connected to each other by radial nerves. The central nervous
      system has a sponge-like structure with many lacunae filled with cell bodies,
      dorso-ventral muscle fibers, parenchymal cell processes and excretory ducts. The
      existence of this sponge-like nervous tissue structure is discussed in relation
      to the still incomplete centralization of the nervous tissue in these organisms,
      to the lack of a true vascular system and to the acoelomate level of
      organization. A comparison with the nervous tissue structure of more advanced
      groups like polyclads and nemertines is suggested.

PMID- 30235913
TI  - The typology and topography of the tarsal chemoreceptors of the blow flies
      Calliphora vicina Robineau-Desvoidy and Phormia terranovae Robineau-Desvoidy and
      the Housefly Musca domestica L.
AB  - A comparative morphological study concerning typology and topography of
      chemoreceptors on the prothoracic legs of Calliphora vicina, Phormia terranovae
      and Musca domestica has been carried out. The typological criteria of Grabowski
      and Dethier ('54) and Hansen and Heumann ('71) were used. A single criterion, the
      shape of the tip, was used to define the different types of chemoreceptors. A
      hairs have a rhombic pore at the side of the tip; B-hairs have an oval pore at
      the tip apex and D-hairs have a rectangular pore under an undulated, cap-like
      structure at the hair tip. A-, B-and D-hairs were found in the tarsomeres of
      Phormia; in Musca and Calliphora only B- and D-hairs were found. An opening and
      closing mechanism may operate on the pores of the tips of the chemoreceptors.
      Chemoreceptors were counted and a topographical map was completed, using SEM
      techniques. Topographical maps are of value in electrophysiological and
      behavioural research, where only a limited optical magnification is possible.

PMID- 30235914
TI  - The fine structure of Gromphadorhina portentosa salivary glands:duct transport
      system.
AB  - The gross external morphology of the salivary glands of Gromphadorhina portentosa
      is described from light, scanning, and transmission electron microscopic
      observations. Various techniques, such as cryofracturing and epoxy-fracturing
      followed by plastic removal, were employed. Internally, the transportation system
      is characterized by a cuticle-lined lumen bordered by duct cells. The duct
      collects secretory products, some of which are reabsorbed by duct cells. Products
      are transported to intercalary ducts and eventually to the hypopharynx and/or
      salivary reservoirs. Transmission electron micrographs demonstrate distinctive
      morphological differences between duct cells bordering ductules and those which
      line expanded regions of the duct. Duct cells which surround ductules have a
      microvillous-lined apical border in which the cuticular coat of the lumen may be
      only partially developed. Duct cells in other regions may retain microvilli, or
      the apical plasma membrane may invaginate and vesiculate. In some cells the
      apical region has neither microvilli nor invaginations, but possesses two
      morphologically different forms of microtubules. Some duct cells are
      characterized by the presence of lamellar bodies in the nuclear region and/or
      collagenous material above the basal lamina in the area where the acinar duct
      becomes confluent with the intercalary duct. The plasma membranes between
      adjacent duct cells within acini become convoluted, forming loops filled with
      cytoplasm. These loops, along with contact and septate desmosomes formed between
      membranes, may serve dual functions: adherent mechanisms between cells and/or
      transportation of materials between cells.

PMID- 30235915
TI  - Prerequisites for Appropriate Clinical Staging of Major Psychiatric Disorders.

PMID- 30235916
TI  - Modified Criteria for Diagnosing "Cognitive Frailty".
AB  - The concept of cognitive frailty has recently been proposed by an International
      Consensus Group as the presence of physical frailty and cognitive impairment
      [defined using the Clinical Dementia Ratings (CDR)=0.5], without concurrent
      dementia. However, CDR is difficult to implement and not often available in
      epidemiologic studies or busy clinical settings, and an alternative to CDR is
      required. We suggest an alternative definition of cognitive frailty as: 1)
      physical frailty, 2) more than 1.5 standard deviation below the mean for age-,
      gender-, and education-adjusted norms on any cognitive function test (e.g., the
      Montreal Cognitive assessment test, the Alzheimer's disease assessment scale
      cognitive subscale, verbal learning test, Digit Span, Boston Naming Test, Trail
      Making Test, and Frontal Assessment Battery), and 3) no dependency in
      instrumental activities of daily living. The redefined criteria for cognitive
      frailty would be more feasible to implement and thus more applicable in
      epidemiologic studies and busy clinical settings.

PMID- 30235917
TI  - Peripheral and Central Metabolites Affecting Depression, Anxiety, Suicidal
      Ideation, and Anger in Complex Regional Pain Syndrome Patients Using a Magnetic
      Resonance Spectroscopy: A Pilot Study.
AB  - OBJECTIVE: This study investigated peripheral and central metabolites affecting
      depression, anxiety, suicidal ideation, and anger in complex regional pain
      syndrome (CRPS) patients. METHODS: Metabolite levels were determined in the right
      and left thalamus and insula, in 12 CRPS patients using magnetic resonance
      spectroscopy (MRS). RESULTS: There were positive correlations between valine
      (Val)/tNAA (N-acetylaspartate+N-acetylaspartylglutamate) and the anxiety, and a
      negative correlation between glutamine (Gln)/NAA and the depression. There were
      positive correlations between alanine (Ala)/Gln and the depression and suicidal
      ideation, between glutamate (Glu)/Gln and the depression and suicidal ideation,
      between N-acetylaspartylglutamate (NAAG)/Gln and the depression. There was a
      positive correlation between Ala/NAAG and the trait anger and a negative
      correlation between creatine (Cr)/N-acetylaspartate (NAA) and the trait anger.
      There was a negative correlation between Cr/Glx (Glu+Gln) and the trait anger.
      High hemoglobin and alkaline phosphatase were associated with low pain levels,
      but CO2 and chloride showed positive correlations with pain levels in CRPS
      patients. Peripheral glucose, CO2 and chloride were associated with depression,
      anxiety, anger and suicidal ideation. CONCLUSION: The specific central and
      peripheral metabolites were associated with psychological disorders including
      depression, anxiety, suicidal ideation and anger in CRPS patients, showing
      pathological interactions between a painful body and mind.

PMID- 30235918
TI  - Benzodiazepine-Associated Carcinogenesis: Focus on Lorazepam-Associated Cancer
      Biomarker Changes in Overweight Individuals.
AB  - OBJECTIVE: Cellular, animal, and human epidemiological studies suggested that
      benzodiazepines increase the risk of cancer and cancer mortality. Obesity is also
      clearly linked to carcinogenesis. However, no human studies have examined
      benzodiazepine-associated carcinogenesis as assessed by changes in cancer
      biomarkers. METHODS: A total of 19 patients were recruited, and received a 6-week
      treatment of 0.5 mg lorazepam. The measured cancer biomarkers were angiopoietin-2
      (ANG-2), soluble CD40 ligand, epidermal growth factor, endoglin, soluble Fas
      ligand (sFASL), heparin-binding EGF-like growth factor (HB-EGF), insulin-like
      growth factor binding protein, interleukin (IL)-6, IL-8, IL-18, plasminogen
      activator inhibitor (PLGF), placental growth factor, transforming growth factor
      (TGF)-alpha, tumor necrosis factor (TNF)-alpha, urokinase-type plasminogen (uPA),
      vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D. RESULTS: Six
      cancer biomarkers were significantly increased in all patients as a whole. The
      subgroup analysis revealed a distinct pattern of change. Overweight patients
      showed a significant increase in 11 cancer biomarkers, including ANG-2, sFASL, HB
      EGF, IL-8, PLGF, TGF-alpha, TNF-alpha, uPA, VEGF-A, VEGF-C, and VEGF-D. However,
      normal-weight patients did not show any changes in cancer biomarkers. CONCLUSION:
      Adiposity may have primed the carcinogenic potential, leading to lorazepam
      associated carcinogenesis in overweight patients. Epidemiological studies
      addressing this issue should consider the potential modulator contributing to
      benzodiazepine-associated carcinogenesis.

PMID- 30235920
TI  - Hypomania Induced by Bifrontal Transcranial Direct Current Stimulation in a
      Patient with Bipolar Depression.
AB  - Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation
      technique, has been increasingly used to treat bipolar depression. Researchers
      recently noticed the risk of tDCS-emergent mania/hypomania in depressed patients
      and started to evaluate this risk by launching a meta-analysis. Here we present a
      female with bipolar II depression who rapidly developed hypomanic switching
      during bifrontal tDCS.

PMID- 30235919
TI  - Protein Kinase C Activity and Delayed Recovery of Sleep-Wake Cycle in Mouse Model
      of Bipolar Disorder.
AB  - OBJECTIVE: Previous studies reported the delayed recovery group after circadian
      rhythm disruption in mice showed higher quinpiroleinduced locomotor activity.
      This study aimed to compare not only Protein Kinase C (PKC) activities in
      frontal, striatal, hippocampus and cerebellum, but also relative PKC activity
      ratios among brain regions according to recovery of circadian rhythm. METHODS:
      The circadian rhythm disruption protocol was applied to eight-week-old twenty
      male Institute Cancer Research mice. The circadian rhythm recovery patterns were
      collected through motor activities measured by Mlog system. Depressive and manic
      proneness were examined by forced swim test and quinpirole-induced open field
      test respectively. Enzyme-linked immunosorbent assay was employed to measure PKC
      activities. RESULTS: The delayed recovery group presented greater locomotor
      activities than the early recovery group (p=0.033). The delayed recovery group
      had significantly lower frontal PKC activity than the other (p=0.041). The former
      showed lower frontal/cerebellar PKC activity ratio (p=0.047) but higher
      striatal/frontal (p=0.038) and hippocampal/frontal (p=0.007) PKC activities
      ratios than the latter. CONCLUSION: These findings support potential mechanism of
      delayed recovery after circadian disruption in bipolar animal model could be an
      alteration of relative PKC activities among mood regulation related brain
      regions. It is required to investigate the PKC downstream signaling related to
      the delayed recovery pattern.

PMID- 30235921
TI  - A Phase II Study to Evaluate the Safety and Efficacy of Pegteograstim in Korean
      Breast Cancer Patients Receiving Dose-dense Doxorubicin/cyclophosphamide.
AB  - Purpose: Dose-dense chemotherapy (DD-CT) is a preferred (neo) adjuvant regimen in
      early breast cancer (BC). Although the results of reported randomized trials are
      conflicting, a recent meta-analysis showed improved overall and disease-free
      survival with DD-CT compared to conventional schedules. However, no DD-CT safety
      data for Korean BC patients are available. This phase II study was conducted to
      evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving
      DD-CT. Materials and Methods: Patients with operable (stage I-III),
      histologically confirmed BC received four cycles of intravenous doxorubicin (60
      mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every two weeks as neoadjuvant
      or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on
      day 2 of each cycle. The primary endpoint was the incidence of febrile
      neutropenia (FN). The secondary endpoints were safety and tolerability. Results:
      Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay
      was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD
      CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle
      weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were
      related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients
      (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug
      reactions possibly linked to pegteograstim were abdominal pain, bone pain,
      myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%).
      Conclusion: Dose-dense AC chemotherapy with pegteograstim support is a tolerable
      and safe regimen in Korean early BC patients.

PMID- 30235922
TI  - What is the Best Sampling Method to Monitor the Effect of Endoscopy Reprocessing?

PMID- 30235923
TI  - Sex as a Biological Variable in Research: the New Policy of Balkan Medical
      Journal

PMID- 30235924
TI  - Precise Enzymatic Cleavage Sites for Improved Bioactivity of siRNA Lipo
      Polyplexes.
AB  - Sequence-defined cationic lipo-oligomers are potent siRNA carriers, forming
      stable lipo-polyplexes based on both electrostatic and hydrophobic interactions
      and, after endocytosis and endosomal protonation, facilitating the delivery of
      siRNA into the cytosol. After completion of the nucleic acid delivery process,
      carriers should be readily biodegradable to ensure minimum accumulation of
      amphiphilic molecules that are harmful to lysosomes and other intracellular
      organelles. Endolysosomal enzymes may degrade a surplus of carrier molecules left
      over in lysosomes and thereby facilitate the generation and rapid excretion of
      cleavage products. By solid-phase supported synthesis, a library of sequence
      defined lipo-oligomers was generated containing artificial and natural amino
      acids comprising precise enzymatic cleavage sites. Incorporating either short
      cleavable l-arginine sequences (RR), noncleavable d-arginine linkers (rr), or
      varieties of both tailored the degradability of lipo-oligomers, as demonstrated
      upon incubation with the endolysosomal protease cathepsin B. Cleavage products
      were identified by MALDI-TOF mass spectrometry. The effect of improved
      intracellular degradation on cell tolerability was studied by transfecting Huh7
      eGFPLuc and DU145-eGFPLuc cells. Positioning of enzymatic cleavage sites between
      a lipophilic diacyl domain and an ionizable oligocationic siRNA binding unit
      enabled efficient enzymatic degradation of the carrier and reduced the lytic
      potential under lysosomal conditions. Highly degradable carriers containing at
      least one l-arginine dipeptide linker significantly improved the viability of
      transfected cells without hampering gene silencing activity. Therefore, the
      precise integration of enzymatic cleavage sites in lipo-oligomers is a promising
      strategy toward biocompatible nucleic acid carriers.

PMID- 30235925
TI  - Visible-Light-Mediated Decarboxylative Benzylation of Imines with Arylacetic
      Acids.
AB  - A straightforward method for the visible-light-mediated decarboxylative
      benzylation of imines is reported. The key feature of this method is the use of
      simple primary, secondary, and tertiary arylacetic acids as precursors of benzyl
      radicals, enabling the facile benzylation of a variety of imines under mild
      conditions. A variety of structurally diverse beta-arylethylamines (37 examples)
      was accessed using this method.

PMID- 30235926
TI  - Direct Transfection of Fatty Acid Conjugated siRNAs and Knockdown of the Glucose
      Regulated Chaperones in Prostate Cancer Cells.
AB  - The emerging field of RNAi nanotechnology has led to rapid advances in the
      applications of siRNAs in chemical biology, medicinal chemistry, and
      biotechnology. In our RNAi approach, bioconjugation of linear, V-, and Y-shaped
      RNA templates were designed using a series of saturated and unsaturated fatty
      acids to improve cell uptake and knockdown efficacy of the oncogenic glucose
      regulated proteins (GRPs) in prostate (PC-3) cancer cells. An optimized HCTU
      coupling procedure was developed for tagging variable saturated and unsaturated
      fatty acids onto the 5'-ends of linear and V-shaped RNA templates that were
      constructed by semiautomated solid phase RNA synthesis. Hybridization and self
      assembly of complementary strands yielded linear, V-, and Y-shaped fatty acid
      conjugated siRNAs which were characterized by native PAGE. CD spectroscopy
      confirmed their A-type helix conformations. RP IP HPLC provided trends in
      amphiphilic properties, whereas DLS and TEM confirmed multicomponent self
      assembled structures that were prone to aggregation. Subsequently, the fatty acid
      conjugated siRNA bioconjugates were tested for their RNAi activity by direct
      transfection within PC-3 cells known to overexpress oncogenic GRP activity. The
      siRNA bioconjugates with sense strand modifiers provided more potent GRP
      knockdown relative to the antisense modified siRNAs, but to a lesser extent when
      compared to the unconjugated siRNA controls that were transfected with the
      commercial Trans-IT X2 dynamic delivery system. Flow cytometry revealed that the
      latter may be at least in part attributed to limited cell uptake of the fatty
      acid conjugated siRNAs. Nonetheless, these new constructs represent an entry
      point in modifying higher-order siRNA constructs that may lead to the generation
      of more efficient siRNA bioconjugates for screening important oncogene targets
      and for cancer gene therapy applications.

PMID- 30235927
TI  - Excited-State Proton Transfer to H2O in Mixtures of CH3CN-H2O of a
      Superphotoacid, Chlorobenzoate Phenol Cyanine Picolinium (CBCyP).
AB  - Steady-state and time-resolved fluorescence techniques were employed to study a
      superphotoacid with a p Ka* of ~-7, the chlorobenzoate phenol cyanine picolinium
      salt (CBCyP) in acetonitrile-water mixtures. We found that the time-resolved
      fluorescence is bimodal. The amplitude of the short-time component depends on
      chiwater; the larger chiwater, the greater the amplitude. We found that the
      excited-state proton-transfer (ESPT) rate constant, kPT, is >=5 * 1012 s-1 in
      mixtures of chiwater >= 0.08, whereas in neat water, kPT = 6 * 1012 s-1. The long
      time component has a lifetime of 50 ps at chiwater = 0.75. We attribute this time
      component to the CBCyP molecules that are not hydrogen-bonded to H2O clusters.
      The results suggest that the ESPT rate constant to water in acetonitrile-water
      mixtures depends only slightly on the water cluster size and structure
      surrounding the CBCyP molecule. We attribute the independence of the ESPT rate on
      the average water-cluster size to the large photoacidity of CBCyP. QM TD-DFT
      calculations found that in the excited-state the RO-(S1) species that is formed
      by the ESPT process is more stable than the ROH(S1) species by -5 kcal/mol when
      four water molecules accept the proton, and when six water molecules accept the
      proton, the RO-(S1) drops to -10 kcal/mol. The calculations show that energy
      stabilities are kept constant in implicit CH3CN-H2O solvent mixtures of
      dielectric constant of epsilon >= 45.

PMID- 30235928
TI  - Bioinspired Amphiphilic Peptide Dendrimers as Specific and Effective Compounds
      against Drug Resistant Clinical Isolates of E. coli.
AB  - Evolution-derived natural compounds have been inspirational for design of
      numerous pharmaceuticals, e.g., penicillins and tetracyclines. Herein, we present
      a bioinspired strategy to design peptide dendrimers for the effective therapy of
      E. coli infections where the selection of appropriate amino acids and the mode of
      their assembly are based on the information gained from research on membranolytic
      natural antimicrobial peptides (AMP's). On the molecular level two opposite
      effects were explored: the effect of multiple positive charges necessary for
      membrane disintegration was equilibrated by the anchoring role of tryptophanes.
      Indeed, a series of Trp-terminated dendrimers exhibited high potency against
      clinical isolates of antibiotic resistant ESBL E. coli strains, stability in
      human plasma along with very low hemo- and genotoxicity. Investigation of the
      underlying antimicrobial mechanism indicated that the dendrimers studied at
      minimal inhibitory concentration showed weak permeability toward membranes. Solid
      state 2D NMR studies revealed their presence on and inside the model membranes.
      Therefore, their biological properties might be explained by targeting of extra-
      or intracellular receptors. Our results point to a new approach to design novel
      branched antimicrobials with high therapeutic index.

PMID- 30235931
TI  - In This Issue, Volume 13, Issue 9.

PMID- 30235929
TI  - Palladium-Catalyzed Catellani-Type Bis-silylation and Bis-germanylation of Aryl
      Iodides and Norbornenes.
AB  - A palladium-catalyzed three-component reaction of aryl iodides, norbornenes, and
      hexamethyldisilane/hexamethyldigermane has been developed for the assembly of
      highly functionalized disilanes/digermanes. The potential synthetic utility of
      this methodology was highlighted by the late-stage manipulations of natural
      products and the iterative C-H bis-silylation for the synthesis of highly
      decorated arenes.

PMID- 30235932
TI  - Effects of Upper Airway Surgery on Daytime Sleepiness in Nonobese Patients with
      Obstructive Sleep Apnea/Hypopnea Syndrome.
AB  - INTRODUCTION:: The aim of this study was to evaluate the effects of upper airway
      surgery on daytime sleepiness in nonobese patients with obstructive sleep
      apnea/hypopnea syndrome (OSA). METHODS:: This retrospective study included 121
      consecutive adult nonobese patients with OSA from a tertiary academic medical
      center. Patients with OSA who refused continuous positive airway pressure
      therapy, or in whom it was unsuccessful, and then underwent OSA surgery were
      enrolled. Evaluations of excessive daytime sleepiness using the Epworth
      Sleepiness Scale (ESS) and major parameters of objective full-night
      polysomnography were collected preoperatively and at least 3 months
      postoperatively. Statistical analysis was performed using the Wilcoxon signed
      rank test and Wilcoxon rank sum test. RESULTS:: When pre- and postoperative ESS
      and polysomnographic parameters were compared in all patients, ESS scores,
      apnea/hypopnea index, and snoring index showed statistically significant
      improvements ( P = .007, P < .001, and P < .001, respectively). When patients
      were classified into mild, moderate, and severe OSA groups, snoring index had
      statistically significant improvements in all 3 groups, and apnea/hypopnea index
      had statistically significant decreases in the moderate and severe OSA groups.
      Although reductions in ESS scores were found in all 3 groups, the most
      statistically significant improvement was noted only in the severe OSA group.
      CONCLUSIONS:: OSA surgery can improve daytime sleepiness in nonobese patients
      with OSA, especially for patients with severe OSA. This study elucidates the
      effects of OSA surgery on daytime sleepiness by excluding the major confounding
      factor of obesity. This study adds to the literature on the effects of upper
      airway surgery for nonobese patients with OSA on daytime quality of life.

PMID- 30235933
TI  - Training to Improve Communication Quality: An Efficient Interdisciplinary
      Experience for Emergency Department Clinicians.
AB  - Patient-provider communication has been recognized as a critical area of focus
      for improved health care quality, with a mounting body of evidence tying patient
      satisfaction and provider communication to important health care outcomes.
      Despite this, few programs have been studied in the emergency department (ED)
      setting. The authors designed a communication curriculum and conducted trainings
      for all ED clinical staff. Although only 72% of clinicians believed the course
      would be a valuable use of their time before taking it, 97% reported that it was
      a valuable use of their time after ( P < .001). Pre-course self-evaluation of
      knowledge, skill, and ability were high. Despite this, post-course self-efficacy
      improved statistically significantly. This study suggests that it is possible, in
      a brief training session, to deliver communication content that participants felt
      was relevant to their practice, improved their skills and knowledge, changed
      their attitude, and was perceived to be a valuable use of their time.

PMID- 30235935
TI  - Current Indications for Transnasal Esophagoscopy: An American Broncho
      Esophagological Association Survey.
AB  - INTRODUCTION:: The aim of this study was to evaluate the current indications for
      and clinical factors influencing the use of transnasal esophagoscopy (TNE).
      METHODS:: An online survey was sent to American Broncho-Esophagological
      Association members, including questions on demographics, indications, and
      factors influencing the use of TNE. RESULTS:: Sixty of 251 members (24%)
      completed the survey. Ninety-three percent of respondents reported academic
      practices, while 98% practice in medium to large urban settings. Thirty-five
      (58%) completed laryngology fellowships. Mean monthly TNE procedure count was
      7.15 (range, <1-35). The most common indications were dysphagia (82%), biopsy
      (50%), and laryngopharyngeal reflux (47%). Chronic cough, head and neck cancer
      screening, gastroesophageal reflux (GER), and tracheoesophageal puncture were
      also commonly reported indications (44% each). For laryngopharyngeal reflux and
      GER, most respondents perform TNE for recalcitrant disease following a medical
      trial of at least 3 months. Long-standing GER symptoms, documentation of GER on
      pH and impedance testing, and abnormal findings on previous esophagoscopy lead to
      greater TNE use. Specific dysphagia indications included abnormal esophagographic
      findings (70%), history or examination localizing to the esophagus (60%), solid
      dysphagia only (53%), and solid and/or liquid dysphagia (40%). The primary sites
      most likely to prompt TNE use for head and neck cancer surveillance were the
      esophagus (92.3%) and hypopharynx (84.6%). Balloon dilation was the most common
      indication for which respondents do not currently perform TNE but would like to
      (n = 8). CONCLUSIONS:: TNE indications have not been well established. According
      to respondents from the American Broncho-Esophagological Association, TNE is most
      commonly used for dysphagia and laryngopharyngeal reflux and slightly less so for
      GER and head and neck cancer screening and surveillance. Several clinical
      indicators were identified that influence the decision to perform TNE.

PMID- 30235934
TI  - The 'Necessity-Concerns Framework' as a means of understanding non-adherence by
      applying polynomial regression in three chronic conditions.
AB  - Objective The 'Necessity-Concerns Framework' is an important framework which can
      support healthcare professionals in targeting patients' medication beliefs and
      decisions on adherence. Our aim was to determine how the interdependence of
      'necessity' and 'concerns' beliefs for medication adherence compares across three
      chronic conditions. Methods Patients diagnosed with asthma, cardiovascular
      conditions or diabetes attending out-patient clinics completed a self
      administered questionnaire. The questionnaire gathered information regarding
      demographics, medication adherence using the 'Tool for Adherence Behaviour
      Screening', presence of unused medication in households and medication beliefs
      using the 'Beliefs about Medicines Questionnaire-Specific'. Polynomial regression
      was applied to determine the multidimensional interdependence of 'necessity' and
      'concerns' beliefs for adherence. P-values <= 0.05 were taken to be significant.
      Results Confirmatory polynomial regression rejected the differential score model
      in all three groups. For each condition, exploratory polynomial regression found
      that linear terms indicated the best fitting model for predicting adherence. In
      all groups, adherence increased as necessity beliefs increased and concerns
      decreased. Patients suffering from cardiovascular conditions and diabetes with
      low necessity and low concerns beliefs reported higher medication adherence
      compared to those with high necessity and high concerns beliefs. Discussion
      Alleviating patients' concerns can enhance medication adherence and potentially
      curb the issue of medication wastage.

PMID- 30235936
TI  - Solid Fuel Use and Risks of Respiratory Diseases: A Cohort Study of 280,000
      Chinese Never-Smokers.
AB  - RATIONALE: Little evidence from large-scale cohort study exists about the
      relationship of solid fuel use with hospitalization and mortality from major
      respiratory diseases. OBJECTIVES: To examine the associations of solid fuel use
      and risks of acute and chronic respiratory diseases. METHODS: A cohort study of
      277,838 Chinese never-smokers with no prior major chronic diseases at baseline.
      During 9-years follow-up, 19,823 first hospitalization episodes or deaths from
      major respiratory diseases, including 10,553 chronic lower respiratory disease
      (CLRD), 4,398 chronic obstructive pulmonary disease (COPD), and 7,324 acute lower
      respiratory infection (ALRI) were recorded. Cox regression yielded adjusted
      hazard ratios (HRs) for disease risks associated with self-reported primary
      cooking fuel use. MEASUREMENTS AND MAIN RESULTS: Overall 91% of participants
      reported regular cooking, with 52% using solid fuels. Compared with clean fuels
      users, solid fuel users had adjusted HR of 1.36 (95%CI 1.32-1.40) for major
      respiratory diseases, whereas those who switched from solid to clean fuels had
      weaker HR (1.14, 1.10-1.17). The HRs were higher in wood (1.37, 1.33-1.41) than
      coal users (1.22, 1.15-1.29) and in those with prolonged use (>=40 years: 1.54,
      1.48-1.60; <20 years: 1.32, 1.26-1.39), but lower among those who used ventilated
      than non-ventilated cookstoves (1.22, 1.19-1.25 versus 1.29, 1.24-1.35). For
      CLRD, COPD and ALRI, the HRs associated with solid fuel use were 1.47 (1.41
      1.52), 1.10 (1.03-1.18) and 1.16 (1.09-1.23), respectively. CONCLUSIONS: Among
      Chinese adults, solid fuel use for cooking was associated with higher risks of
      major respiratory disease admissions and death and switching to clean fuels or
      use of ventilated cookstoves had lower risk than those who were not.

PMID- 30235937
TI  - Design, validation and testing of short text messages for an HIV mobile-health
      intervention to improve antiretroviral treatment adherence in Mexico.
AB  - Mobile Health (mHealth) interventions have become effective strategies to
      increase adherence to antiretroviral treatment (ART) in people living with HIV
      (PLWH). mHealth interventions use phone calls, e-mails, smartphone apps or short
      text messages (SMS) as reminders of medical appointments or ART adherence. SMS
      are a highly accepted mHealth strategy. Systematized processes to validate SMS
      tailored to end-user preferences are required to increase the effectiveness of
      mHealth interventions. We describe a structured approach to develop a set of SMS
      tailored to Mexican HIV+ individuals, focused on improving ART adherence and
      healthcare appointments. The process included three sequential phases: SMS design
      by HIV-healthcare professionals, validation by expert referees, and testing by
      PLWH. A set of 108 SMS in four categories (motivational self-healthcare messages,
      ART-collection, medical and laboratory-appointment reminders) was designed.
      Expert referees assessed 94.5% of messages as adequate, 65.7% as useful. Seventy
      one SMS were further tested by PLWH, who considered 100% of SMS to be
      understandable and 57.7% useful. SMS had adequate intra-judge agreement scores
      for clarity and acceptability (ICC-2 = .08-.49). Qualitative feedback from expert
      referees and PLWH was incorporated into SMS. A final set of 41 highest-rated SMS
      was obtained. Careful validation of SMS could increase the effectiveness of
      mHealth interventions.

PMID- 30235938
TI  - Exosomal miR-1246 in body fluids is a potential biomarker for gastrointestinal
      cancer.
AB  - AIM: The aim was to systematically evaluate whether exosomal miRNAs could be
      regarded as potential minimally invasive biomarkers of diagnosis for
      gastrointestinal cancer. METHODS: A systematic review and meta analysis of
      exosomal miRNA expression in gastrointestinal cancer were performed. RESULTS: A
      total of 370 articles were retrieved from PubMed and EMBASE. The summary receiver
      operating characteristic curves of three miRNAs (miR-21, miR-1246 and miR-4644)
      were drawn, miR-21, miR-1246 and miR-4644 exhibited sensitivities of 0.66, 0.920
      and 0.750, respectively; specificities were 0.87, 0.958 and 0.769, respectively;
      and areas under the curve for discriminating gastrointestinal cancer patients
      from control subjects were 0.876, 0.969 and 0.827, respectively. CONCLUSION:
      Exosome miR-1246 had the highest level of diagnostic efficiency, which indicated
      that miR-1246 could be a biomarker.

PMID- 30235939
TI  - Early intervention for autism: Are we prioritizing feasibility at the expenses of
      effectiveness? A cautionary note.

PMID- 30235940
TI  - High prevalence of non-adherence to antiretroviral therapy among undisclosed HIV
      infected children in Ghana.
AB  - Adherence to antiretroviral therapy (ART) remains one of the greatest obstacles
      in pediatric HIV care. We sought to determine the prevalence of adherence to ART
      among undisclosed HIV-infected children and adolescents in Ghana. We analyzed
      baseline data from HIV-infected children and adolescents aged 7-18 years old
      enrolled in the SANKOFA Pediatric HIV disclosure intervention study in Ghana.
      Antiretroviral medication adherence was measured using caregiver 3-day recall;
      child 3-day recall; and pharmacy records for antiretroviral time-to-refill. Four
      hundred and twenty child-caregiver dyads were enrolled from January 2013 to June
      2016. The median adherence (interquartile range), as measured by time-to-refill,
      was 93.2% (68.0%-100.0%). However, only 47.5% of children had >=95% adherence
      ("good adherence") using time-to-refill data. Children of caregivers who had
      received secondary or higher level of education versus no school (aOR, 2.90, 95%
      Confidence Interval, CI 1.29-6.56), p = 0.010) or elementary education only (aOR,
      2.20, CI, 1.24-3.88, p = 0.007) were more likely to have "good adherence"
      (>=95%). In this cohort of children unaware of their HIV positive status, median
      ART adherence rate was sub-optimal (by World Health Organization definition)
      while 38% had poor adherence (<85%).

PMID- 30235941
TI  - Risk factors for perinatal transmission of HIV among women attending prevention
      of mother-to-child transmission clinics in Northwest Nigeria.
AB  - Despite the effectiveness of antiretroviral therapy (ART) in the prevention of
      mother-to-child transmission of HIV (PMTCT), some HIV-infected women in PMTCT
      care are at risk of transmitting HIV to their babies. Using a 1:1 unmatched case
      control study design, we assessed the risk factors for perinatal transmission
      among women who received ART for PMTCT in Sokoto State, Nigeria. Data were
      abstracted from medical records of cases (94 HIV-infected babies) and controls
      (94 HIV-uninfected babies) and their mothers who accessed PMTCT services in three
      purposefully selected secondary health facilities. We conducted univariate and
      multivariate logistic regressions to determine if sociodemographic
      characteristics, time of enrolment, type of maternal ART, receipt of infant
      antiretroviral (ARV) prophylaxis, place of delivery, or feeding practice were
      associated with HIV infection among HIV-exposed babies. Sixteen percent of the
      mothers of babies in the case group had early enrolment while 90% of those in the
      control group enrolled early. Infant prophylaxis was received in 54% of cases and
      95% of controls. In both groups, 99% of the mothers practiced mixed feeding. In
      the univariate analysis, factors that were significantly associated with HIV
      infection were religion (islam), rural residence, late? enrolment, and non
      receipt of infant ARV prophylaxis. In the multivariate analysis, rural residence
      (Adjusted odds ratio (aOR) = 8.01, 95% CI = 1.79-35.78), late enrolment (aOR =
      41.72, 95% CI = 15.16-114.79), and non-receipt of infant ARV prophylaxis (aOR =
      4.1, 95% CI = 1.18-14.33) remained statistically significant. Findings from this
      study indicate that eliminating MTCT in Nigeria requires interventions that will
      enhance timely access of ART by mother-baby dyads.

PMID- 30235943
TI  - Latent class analysis of a syndemic of risk factors on HIV testing among black
      men.
AB  - Syndemic methodology has been employed in several studies of HIV-related outcomes
      affecting Black men who have sex with men (BMSM) and rarely in Black heterosexual
      men. In contrast to the most common method for assessing syndemics, the use of a
      syndemic component index, latent class analysis can identify unique combinations
      of risk factors that may form a syndemic. Analyzing a primarily heterosexual
      sample of 1,786 Black men from the 2015 Behavioral Risk Factor Surveillance
      System (BRFSS), we used a 4 latent class model based on depression diagnosis,
      poverty, and healthcare access to predict ever having been HIV tested. Class 1
      was characterized by low proportions of all the risk factors. Class 2 had
      relatively high healthcare barriers, being the most likely to not have a personal
      doctor (.8175) and the most likely to have no routine checkup in the past year
      (.6327) but had relatively low depression diagnosis and poverty. Class 3 had
      relatively high poverty (.8853), but generally low barriers to healthcare access.
      Class 4 was characterized by high proportions of all the risk factors. Using log
      binomial regression models, there was a significantly lower prevalence of ever
      having been HIV tested among class 3 (PR = 0.69, 95% CI 0.49, 0.98) and class 4
      (PR = 0.49, 95% CI 0.28, 0.84) compared to class 1. When adjusting for education,
      age, and marital status, the associations were attenuated but still significant
      for class 3 (aPR = 0.71, 95% CI 0.52, 0.96) and class 4 (aPR = 0.60, 95% CI 0.46,
      0.78). Latent class analysis may better serve syndemic research aims in
      understanding HIV-related outcomes among high-risk populations. Future research
      using this method to evaluate HIV testing outcomes among BMSM is recommended.

PMID- 30235942
TI  - Brain Death-Induced Inflammatory Activity is Similar to Sepsis-Induced Cytokine
      Release.
AB  - Brain death (BD) is associated with a systemic inflammation leading to worse
      graft outcomes. This study aimed to compare plasma cytokine values between brain
      dead and critically ill patients, including septic and non-septic controls, and
      evaluate cytokine release kinetics in BD. Sixteen brain-dead and 32 control
      patients (16 with and 16 without sepsis) were included. Plasma cytokines were
      measured by magnetic bead assay after the first clinical exam consistent with BD
      and every 6 hours thereafter, and at the time of study entry in the control
      group. The values for IL-8 and IFN-gamma were higher in brain-dead and septic
      patients than in non-septic patients [IL-8: 80.3 (18.7-169.6) vs. 68.2 (22.4
      359.4) vs. 16.4 (9.2-42.7) pg/mL; P = 0.006; IFN-gamma: 2.8 (1.6-6.1) vs. 3.4
      (1.2-9.0) vs. 0.5 (0.5-1.8) pg/mL; P = 0.012]. TNF showed a clear tendency to
      increase in brain-dead patients [2.7 (1.0-4.8) vs. 1.0 (1.0-5.6) vs. 1.0 (1.0
      1.0) pg/mL; P = 0.051], and IL-6 values were higher in brain-dead patients than
      in non-septic controls [174.5 (104.9-692.5) vs. 13.2 (7.3-38.6) pg/mL; P =
      0.002]. These differences remained even after excluding brain-dead patients who
      also had sepsis ( n = 3). IL-1beta and IL-10 values increased from baseline to
      time point 2 (~6 hours later) [IL-1beta: 5.39 (1.93-16.89) vs. 7.11 (1.93-29.13)
      pg/mL; P = 0.012; IL-10: 8.78 (3.62-16.49) vs. 15.73 (5.49-23.98) pg/mL; P =
      0.009]. BD-induced and sepsis-induced plasma cytokine values were similarly high,
      and both were higher than the observed in non-septic critically ill patients.

PMID- 30235944
TI  - Prevalence, Incidence, and Contributors of Subclinical Atheromatosis,
      Arteriosclerosis, and Arterial Hypertrophy in HIV-Infected Individuals: A Single
      Center, 3-Year Prospective Study.
AB  - Cardiovascular disease (CVD) is an important comorbidity for people living with
      HIV infection (PLWH) in the combined antiretroviral therapy era. We prospectively
      examined the presence of subclinical arterial disease in 138 consecutive CVD
      free, HIV-infected individuals compared to 664 HIV-negative individuals. We
      studied 10 arterial sites in 4 beds using 5 distinct biomarkers of subclinical
      atheromatosis, arteriosclerosis, and hypertrophy and evaluated the association of
      subclinical arterial damage with CVD-related and HIV-related factors at baseline
      and at 3-year follow-up. Atheromatosis, arteriosclerosis, and arterial
      hypertrophy were present in 36.1%, 59.7%, and 34.3% of HIV-infected individuals,
      respectively, at baseline. HIV infection was independently associated with
      carotid atheromatosis and hypertrophy. The presence of carotid atheromatosis was
      independently associated with age, years of smoking, and exposure to
      nonnucleoside reverse transcriptase inhibitors (NNRTIs). The annual incidence of
      atheromatosis, arteriosclerosis, and arterial hypertrophy was 5.5, 18.6, and 12.5
      cases/100 patients, respectively. Carotid atheromatosis progression was
      significantly associated with NNRTI exposure. People living with HIV infection
      exhibited high prevalence and incidence of subclinical arterial damage and site
      specific predilection for the carotids. These investigations may help optimize
      HIV-specific CVD prediction models. The NNRTIs may contribute to atheromatosis,
      emphasizing the need to consider the atherogenic potential of antiretroviral
      drugs in management strategies.

PMID- 30235945
TI  - Survival of encapsulated probiotics in pasteurized grape juice and evaluation of
      their properties during storage.
AB  - In this study, probiotic bacteria such as Lactobacillus acidophilus and
      Bifidobacterium bifidum were encapsulated in alginate beads with a mean diameter
      of 54.25 +/- 0.18 um by internal gelation. Encapsulated and free cells as control
      samples were then added to the pasteurized grape juice and stored for 60 days. At
      the end of the storage period, the survivability of the bacteria in the
      encapsulated samples was significantly ( P<0.05) higher than that in the free
      cells (8.67 +/- 0.12 and 7.57 +/- 0.08 log cfu mL-1 for L. acidophilus and 8.27
      +/- 0.05 and 7.53 +/- 0.07 log cfu mL-1 for B. bifidum for encapsulated and free
      forms, respectively). The results generally showed a decrease in  degrees Brix,
      pH, and color, whereas acidity and turbidity have increased the in probiotic
      grape juice after the storage period of 60 days. For all treatments, the numbers
      of surviving cells were more than the recommended minimum (107 cfu g-1) at the
      end of the storage period.

PMID- 30235947
TI  - Facial Attractiveness as a Function of Athletic Prowess.
AB  - We investigate the relationship between facial attractiveness and athletic
      prowess. We study the connection between subjective facial attractiveness
      (measured on a 5-point scale of judged facial attractiveness) and athletes by
      gender and age of respondents. Five age classes were investigated in Studies 1-5:
      preadolescents (average age: 8.85 years: n = 92), adolescents (average age: 15.8
      years; n = 82), young adults (average age: 21.6 years; n = 181), middle-aged
      adults (average age: 47.5 years; n = 189), and older adults (65 years old; n =
      183). The findings show that world-class athletes are perceived as more facially
      attractive than amateur athletes, with women athletes perceived as more facially
      attractive than men, and these findings generally occur to a greater extent for
      female than male respondents. These findings hold for preadolescents,
      adolescents, young adults, and older adults. However, results were mixed for
      middle-aged adults where generally amateur athletes were evaluated more
      attractive than world-class and men athletes more attractive than women.

PMID- 30235946
TI  - Comorbid interpretation and expectancy bias in social anxiety and alcohol use.
AB  - BACKGROUND: In two studies, the present research examined whether being high in
      both social anxiety and alcohol use disorder symptoms is associated with a
      comorbid interpretation and expectancy bias that reflects their bidirectional
      relationship. DESIGN: Cross-sectional, quantitative surveys. METHODS: Measures of
      social anxiety and alcohol use disorder symptoms, as well as an interpretation
      and expectancy bias task assessing biases for social anxiety, drinking, and
      comorbid social anxiety and drinking. RESULTS: In Study 1 (N = 447), individuals
      high (vs. low) in social anxiety had stronger social threat bias and individuals
      high (vs. low) in alcohol use disorder symptoms had stronger drinking bias. Those
      high in both social anxiety and alcohol use disorder symptoms endorsed
      interpretations and expectancies linking social interaction with alcohol use.
      Comorbid bias predicted membership into the high social anxiety/drinking group,
      even after taking into account single-disorder biases. In Study 2 (N = 325),
      alcohol use disorder symptoms predicted drinking bias and social anxiety symptoms
      predicted social anxiety bias. Alcohol use disorder symptoms, social anxiety
      symptoms, and their interaction predicted comorbid interpretation and expectancy
      bias. CONCLUSION: Results indicate unique cognitive vulnerability markers for
      persons with comorbid social anxiety and alcohol use disorder symptoms, which may
      improve detection and treatment of this serious comorbidity.

PMID- 30235949
TI  - Is music-with-movement intervention better than music listening and social
      activities in alleviating agitation of people with moderate dementia? A
      randomized controlled trial.
AB  - Aim Interactive music intervention is generally perceived as more effective on
      clinical outcomes than a receptive approach because it can better engage the
      people with dementia. The aim of this study is to compare the effects of the 6
      week music-with-movement intervention on agitation of people with moderate
      dementia, music listening and social activity. Methods A multi-centre randomized
      controlled trial was conducted on 165 nursing home residents with moderate
      dementia. The participants were randomly allocated into three groups: music-with
      movement, music listening or social activities groups. Participants in the music
      with-movement group listened to preferred music and moved their body parts for 45
      minutes, twice a week for 6 weeks. While the participants in the music listening
      group only listened to their preferred music and social activity group chatted
      with the other group members. The agitation level was examined with the Chinese
      Cohen-Mansfield Agitation Inventory - Nursing Home version. Total scores and sub
      scores (physically aggressive, physical non-aggressive, verbal aggressive and
      verbal non-aggressive) were compared at baseline, at post-intervention and 6
      weeks post-intervention. Results The results showed that there are no significant
      differences in agitation among three groups. Repeated measures univariate
      analyses revealed that all three groups yielded significant improvement in
      agitation from baseline to post-intervention, of which music-with-movement
      presented the largest effect size. Conclusion This study showed that interactive
      or receptive type of music intervention or social activities may be helpful in
      managing agitation although there is no statistically significant difference
      among them.

PMID- 30235948
TI  - Deploying unqualified personnel in health records practice: Role substitution or
      quackery? Implications for health services delivery in Nigeria.
AB  - Healthcare professionals are obliged to work collaboratively regardless of their
      professional differences in order to provide the highest possible standard of
      care to patients. However, this type of collaboration can also lead to role
      substitution and, in effect, engagement of unqualified personnel in all health
      professions, including the health information management profession. This is a
      particular problem in developing nations such as Nigeria, where this trend has
      the potential to undermine the delivery of health services, the quality and the
      confidentiality of health information and trust between patients and healthcare
      professionals. To clarify and protect the professional identity of qualified
      health information management professionals in Nigeria and to prevent other
      experts who also work in health facilities (e.g. IT specialists, librarians) from
      claiming membership of the profession, the nomenclature for the health
      information management profession has been changed to health records and
      information management profession.

PMID- 30235950
TI  - The art and science of non-evaluation evaluation.
AB  - This essay considers some limitations of programme theory evaluation in relation
      to healthcare policies. This approach, which seeks to surface 'programme
      theories' or construct 'logic models', is often unable to account for empirical
      observations of policy implementation in real-world contexts. I argue that this
      failure stems from insufficient theoretical elaboration of the social, cultural
      and political dimensions of healthcare policies. Drawing from institutional
      theory, critical theory and discourse theory, I set out an alternative agenda for
      policy research. I illustrate the issues with respect to programme theory
      evaluation with examples from my experience of research on large-scale strategic
      change in the English NHS.

PMID- 30235951
TI  - Improving access to health services in Canada.
AB  - The Commonwealth Fund 2017 report ranked Canada's healthcare system low in access
      to care and last among all 11 counties studied in terms of timeliness of care.
      While long wait times for certain elective surgical procedures appear to be
      emblematic of Canadian Medicare, they are not inevitable. Wait times could be
      improved by focusing on public awareness and measurement of wait times and
      improving the appropriateness, efficiency (eg, with implementation of single
      entry models for surgical referrals and greater use of ambulatory surgery), and
      productivity of surgical care (eg, by activity-based funding for surgical
      procedures and by reducing the cost of perioperative care). Ideas on how
      physician leaders can build on recent accomplishments are provided.

PMID- 30235952
TI  - Cumulative trauma, emotion reactivity and salivary cytokine levels following
      acute stress in healthy women.
AB  - BACKGROUND AND OBJECTIVES: To better understand how trauma leads to poor health,
      this study examined whether cumulative trauma and emotion reactivity contribute
      to pro- (IL-1beta) and anti-inflammatory (IL-10) salivary cytokine levels after
      stress. DESIGN: Seventy-three women, screened to be physically and mentally
      healthy, completed an acute stress paradigm and measures of lifetime trauma
      exposure. METHOD: Saliva was collected 10 min before (i.e., baseline) and 35 min
      after the onset of a 10-min stressor. State negative and positive emotion were
      measured at baseline and post-stress. RESULTS: Most participants reported
      exposure to at least one trauma, with a mean of five. Cumulative trauma was
      associated with higher post-stress IL-1beta and IL-1beta/IL-10, but not with IL
      10 or changes in emotion. Declines in positive emotion correlated with greater
      post-stress IL-1beta. CONCLUSIONS: These findings suggest that both cumulative
      trauma exposure and positive emotion have implications for salivary cytokine
      responses to acute stress. The inclusion of healthy women strengthens internal
      validity, and increases confidence that observed associations between trauma and
      salivary cytokine responses can be attributed to trauma, rather than to
      confounding health problems. This study adds to the growing literature examining
      how trauma may connect to cytokines, and ultimately, poor health.

PMID- 30235953
TI  - The Influence of Spatial Design on Team Communication in Hospital Emergency
      Departments.
AB  - OBJECTIVE: To identify spatial design factors that influence informal
      interprofessional team-based communication within hospital emergency departments
      (EDs). BACKGROUND: Effective team communication in EDs is critical for
      interprofessional collaborative care and prevention of serious errors due to
      miscommunication. Limited evidence exists about how informal communication in EDs
      is shaped by the physical workspace and how workplace design principles can
      improve the quality of ED team communication. METHOD: Two health services with
      four hospital sites in Victoria, Australia, participated. A multistage mixed
      methods approach used (1) an anonymous online communication network survey ( N =
      103) to collect data on patterns and locations of informal interprofessional team
      communication among ED staff, (2) focus groups ( N = 37) and interviews ( N = 3)
      using photoelicitation to understand the perspectives of ED staff about how
      spatial design influences team communication, and (3) validity testing of
      preliminary findings with executives and ED managers at the participating sites.
      RESULTS: Informal communication with peers and within discipline groups on
      nonspecific areas of the ED was most common. Three key factors influenced the
      extent to which ED workspaces facilitated informal communication: (1) staff
      perceptions of privacy, (2) staff perceptions of safety, and (3) staff
      perceptions of connectedness to ED activity. CONCLUSION: Our research supports
      the proposition that ED physical environments influence informal team
      communication patterns. To facilitate effective team communication, ED workspace
      spatial designs need to provide visibility and connectedness, support and capture
      "case talk," enable privacy for "comfort talk," and optimize proximity to
      patients without compromising safety.

PMID- 30235954
TI  - Caregiver burden after stroke: changes over time?
AB  - INTRODUCTION AND AIM: Many caregivers of stroke patients experience a high
      burden. This study aims to describe the course of burden in individual caregivers
      in the first year after stroke. METHODS: This study is part of the Stroke Cohort
      Outcomes of REhabilitation study, a multicentre, longitudinal cohort study
      including consecutive stroke patients admitted to two rehabilitation facilities.
      Caregivers were asked to complete the Caregiver Strain Index and questions on
      their sociodemographic characteristics 6 and 12 months post admission. Patients'
      sociodemographic and clinical characteristics were extracted from medical
      records. RESULTS: A total of 129 caregivers were included, 72 completed the
      Caregiver Strain Index twice. Of them, 19 (26.4%) were men, median age 59 (range
      27-78) years. A consistently high or low burden was reported by 15 (20.8%) and 49
      (68.1%), respectively, whereas 8 (11.1%) reported a high burden at either 6 (n =
      3) or 12 months (n = 5). DISCUSSION: In the majority of caregivers of stroke
      patients the perceived caregiver burden is consistent over time. However, as in
      11.1% caregiver burden changes from 6 to 12 months, caregiver burden should be
      measured repeatedly until 12 months after stroke. Caregivers living together with
      a patient who suffered a haemorrhagic stroke seem to be more at risk for a high
      burden. Implications for rehabilitation Many caregivers of stroke patients
      experience a high burden. The Caregiver Strain Index score at 6 months is a good
      predictor for the score at 12 months. In some caregivers the high burden is not
      yet present at 6 months, therefore monitoring caregiver burden throughout the
      first year after stroke seems warranted. Caregivers living together with a
      patient who suffered a haemorrhagic stroke seem to be more at risk for a high
      burden.

PMID- 30235955
TI  - Is adaptive learning the way forward?

PMID- 30235956
TI  - A literature review of herpes simplex virus hepatitis in pregnancy.
AB  - PURPOSE: Hepatitis due to herpes simplex virus (HSV) during pregnancy is rare, it
      is often not included in the differential disease. However, hepatitis leads to
      maternal death; hence, early diagnosis is necessary. Hepatic enzyme elevation in
      late pregnancy is often associated with obstetric-related diseases, such as acute
      gestational fatty liver and HELLP syndrome (hemolytic anemia, elevated liver
      enzymes, low platelet count). These pregnancy-related diseases often improve
      maternal condition after completion of pregnancy, but in patients with HSV
      hepatitis, invasive treatment, such as cesarean section, may lead to
      deterioration of maternal condition after completion of pregnancy. A systematic
      review was conducted to extract necessary factors to avoid maternal death caused
      by herpetic hepatitis. METHODS: In 24 cases reported since 1991, age, onset
      gestational weeks, initial symptoms, days from onset of symptoms to consultation,
      diagnosis method, treatment method, maximum liver escape enzyme value during
      hospitalization, bilirubin value, international normalized ratio value, and
      fetal/neonatal prognosis were extracted, and the relationship between maternal
      death group (n = 6) and maternal alive group (n = 18) was statistically analyzed.
      RESULTS: Fever as an initial symptom was observed in all cases. Maternal death
      did not occur in patients administered with acyclovir (ACV) as empiric therapy.
      No difference was found between the two groups in other factors. CONCLUSION:
      Early diagnosis and treatment of herpetic hepatitis during pregnancy are
      important, as well as administration of empiric ACV concurrently with noninvasive
      diagnosis when a pregnant woman has elevated liver enzyme accompanied by fever in
      late pregnancy.

PMID- 30235957
TI  - Neuroform Atlas stent deployment through the Barrel vascular reconstruction
      device for the treatment of a wide-necked acutely ruptured basilar aneurysm.
AB  - Background The Barrel vascular reconstruction device is an electrolytically
      detachable laser-cut closed-cell stent used for neck reconstruction in wide
      necked bifurcation aneurysms to support coiling without necessitating dual stent
      implantation. The purpose is to lower the metal-to-artery ratio and its inherent
      risk of thromboembolic complications of multiple stents. Case description A 53
      year-old woman presenting with subarachnoid hemorrhage due to acutely ruptured
      basilar tip aneurysm underwent emergency endovascular embolization with the
      Barrel vascular reconstruction device. Since the stent did not cover the entire
      neck of the aneurysm, an Atlas stent was released in a Y configuration through
      the Barrel. The Neuroform Atlas correctly opened through the Barrel and allowed
      the complete exclusion of the aneurysm. Conclusion If necessary, releasing a
      Neuroform Atlas through a Barrel vascular reconstruction device is a feasible
      technique.

PMID- 30235958
TI  - Risk factors for relaparotomy after cesarean delivery and related maternal near
      miss event due to bleeding.
AB  - AIM: To define the risk factors for relaparotomy after cesarean delivery (RLACD)
      and related maternal near-miss event due to bleeding. METHODS: In this
      retrospective descriptive case-control study, women who underwent RLACD (n = 46)
      only for bleeding between 2012 and 2017 were reviewed. Factors that could predict
      relaparotomy and related near-miss event were evaluated. Maternal
      characteristics, laboratory findings and surgical features were compared with a
      control group (n = 230) that included noncomplicated cesarean deliveries (CD).
      Logistic regression analysis was used to identify independent factors for
      relaparotomy. RESULTS: RLACD for bleeding was required in 0.26% of patients and
      the incidence increased gradually over years (0.16% in 2013 versus 0.44% in
      2017). Mean interval between CD and subsequent relaparotomy was 15.7 +/- 3.2
      hours. The sources of bleeding in descending order of frequency included; uterine
      fundus and placental bed (39.1%), cervix (21.7%), undetermined (17.3%), superior
      epigastric artery (13%), superficial epigastric artery (8.1%). Longer duration of
      CD (adjusted odd ratio (aOR) 1.82, 95% CI 1.02-2.53), increased number of prior
      CDs (aOR 2.51, 95% CI 1.09-5.78), preeclampsia (aOR 3.48, 95% CI 1.21-7.19) were
      found to be independent risk indicators for RLACD. Moreover, longer duration of
      interval between CD and relaparotomy (p = .005), longer relaparotomy duration (p
      = .012) and greater drop in hemoglobin level (p = .001) were found to be the
      predictors of maternal near-miss event. CONCLUSIONS: Patients with identified
      risk factors should be managed properly in order to prevent relaparotomy and near
      miss event after CD. Also, urgent decision of surgical intervention might reduce
      the risk of maternal near-miss event.

PMID- 30235960
TI  - Safety Assessment of PEG-150 Pentaerythrityl Tetrastearate as Used in Cosmetics.
AB  - The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of
      polyethylene glycol (PEG)-150 pentaerythrityl tetrastearate, which functions as a
      viscosity-increasing agent-aqueous in cosmetic products and is being used at
      concentrations up to 5%. Given the chemical structure (large molecule), skin
      penetration is not likely. The available toxicity data and the low ingredient use
      concentrations suggest that systemic toxicity would not be likely even if
      percutaneous absorption were to occur. Additionally, the negative human repeated
      insult patch test data on the undiluted ingredient were deemed sufficient for
      evaluating skin irritation and sensitization potential. The Panel concluded that
      PEG-150 pentaerythrityl tetrastearate is safe in cosmetics in the present
      practices of use and concentration described in this safety assessment.

PMID- 30235959
TI  - Safety Assessment of Tocopherols and Tocotrienols as Used in Cosmetics.
AB  - The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of
      14 tocopherols and tocotrienols and concluded these ingredients are safe as used
      in cosmetics. The tocopherols are reported to function in cosmetics as
      antioxidants or skin-conditioning agents; in contrast, tocotrienols are not
      reported to function as an antioxidants in cosmetics but as a light stabilizer,
      oral care agent, or skin-conditioning agent. The Panel reviewed the new and
      existing animal and clinical data to determine the safety of these ingredients
      and found it appropriate to extrapolate the existing information to conclude on
      the safety of all the tocopherols and tocotrienols.

PMID- 30235961
TI  - Safety Assessment of PEGs Cocamine and Related Ingredients as Used in Cosmetics.
AB  - The Cosmetic Ingredient Review Expert Panel assessed the safety of 47
      polyethylene glycols (PEGs) cocamine and related ingredients, which are reported
      to function mostly as surfactants and antistatic agents. The Panel reviewed the
      relevant data and developed a framework to satisfy previously identified data
      deficiencies for this group of materials as well as extend the scope of related
      materials covered by the analysis. The irritation potential of these ingredients
      is consistent with the surface active properties that are characteristic of
      surfactants. The Panel concluded that the PEGs cocamine and related ingredients
      were safe as ingredients in cosmetic formulations in the current practices of use
      and concentration when formulated to be nonirritating.

PMID- 30235962
TI  - Immunopathological and molecular basis of functional dyspepsia and current
      therapeutic approaches.
AB  - INTRODUCTION: Functional dyspepsia (FD) is widespread with 20% prevalence
      worldwide and a significant economic burden due to health care cost and
      constraints on daily activities of patients. Despite extensive investigation, the
      underlying causes of dyspepsia in a majority of patients remain unknown. Common
      complaints include abdominal discomfort, pain, burning, nausea, early satiety,
      and bloating. Motor dysfunction of the gut was long considered a major cause, but
      recent investigations suggest immune-based pathophysiological and molecular
      events in the duodenum are more probable contributing factors. Areas Covered:
      Inflammatory mediators and immune cells including duodenal eosinophils,
      intraepithelial lymphocytes, and T-cells have been implicated in the underlying
      cause of disease process, as have genetic factors. In this article, we critically
      reviewed findings, identified gaps in knowledge and suggested future directions
      for further investigation to identify targets and develop better therapeutic
      approaches. Expert commentary: Impaired gastric accommodation, slow gastric
      emptying, and increased visceral sensitivity have long been thought of as main
      causal factors of FD. However, more recent identification of eosinophilic
      degranulation and recruitment of T cells that induce mild duodenal inflammation
      are giving rise to new insights into immune-mediated pathophysiology. These
      insights offer promising avenues to explore for immune-mediated therapy in the
      future.

PMID- 30235963
TI  - Preparation of liposomal doxorubicin-graphene nanosheet and evaluation of its in
      vitro anti-cancer effects.
AB  - In recent years there has been much interest in development of multifunctional
      drug delivery systems. In this work, liposomes that contain doxorubicin (Dox), a
      potent anticancer drug, and graphene nanosheets (GNS) were prepared. The GNSs
      have excellent optical properties, such as photoluminescence which enables
      tracking of the liposomes, high absorption in ultra violet region of
      electromagnetic spectrum which can be exploited in photodynamic and photothermal
      therapy, and low toxicity to mammalian cells. Nanoliposomes were prepared using
      the thin film hydration method. Dox and GNSs were loaded to the liposomes during
      the hydration of the lipid film. Liposomes were characterized and the profile of
      in vitro drug release, cellular uptake and cytotoxicity of the prepared liposomes
      on MCF-7 cells were determined. Despite of the earlier reports, the liposomes
      have kept their spherical structures in the presence of GNSs. The cytotoxicity of
      liposomal Dox and GNSs were shown to be higher than the free forms of them. Novel
      nanoliposomes that contain GNSs have provided a multi-functional system with the
      potential of tracking, photodynamic and photothermal therapy. Further
      improvements of this versatile nanosystem would be promising for treatment of
      cancer.

PMID- 30235964
TI  - Transcutaneous bilirubin nomogram for the first 144 hours in Thai neonates.
AB  - OBJECTIVES: To develop an hour-specific transcutaneous bilirubin (TcB) nomogram
      for Thai neonates and to compare the ability of this nomogram with that of
      Bhutani's total serum bilirubin (TSB) nomogram for prediction of significant
      hyperbilirubinemia requiring phototherapy. METHODS: Healthy Thai neonates,
      gestational age >=35-week-gestation and birth weight >=2000 grams were enrolled.
      Neonates who could not attend the postdischarge follow-up at our center were
      excluded. TcB measurements were routinely performed at 6 am and 6 pm using JM103
      transcutaneous bilirubinometer until the neonates were discharged or received
      phototherapy. TcB levels were also measured at least once during 24-72 hours
      after discharge and thereafter depending on the pediatricians' decision. The
      nomogram was developed from the TcB data during age 12-144 hours of neonates who
      did not require phototherapy. The TcB values that obtained predischarge or before
      receiving phototherapy of all neonates were used to determine the predictive
      ability of this nomogram and Bhutani's TSB nomogram. RESULTS: A total of 1071
      neonates were included. Two hundred forty-one neonates (22.5%) required
      phototherapy. The nomogram was constructed using 4834 hour-specific TcB values.
      It provided a good prediction with the area under curve (AUC) of 0.89. The 75th
      percentile tract revealed sensitivity and negative predictive value (NPV) of 87.1
      and 95.4% while that of the 40th percentile tract were 97.9 and 98.5%
      respectively. When Bhutani's nomogram was used, the AUC was 0.84. The sensitivity
      and NPV of the 75th percentile tract were 56.4 and 88.2%, and for the 40th
      percentile tract were 97.1 and 98.0% respectively. CONCLUSION: The newly
      developed TcB nomogram revealed slightly better predictive ability than Bhutani's
      TSB nomogram for term and late preterm Thai neonates who were the population with
      high prevalence of significant hyperbilirubinemia. The 40th percentile curve of
      both nomograms should be considered as an appropriate cut-off level for
      prediction.

PMID- 30235965
TI  - A review of the effects of baclofen and of THC:CBD oromucosal spray on spasticity
      related walking impairment in multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis (MS) is a complex disease with a heterogeneous
      and unpredictable clinical course. Mobility impairment after progressive
      paralyses and muscle tone spasticity is common. Areas covered: The prevalence,
      assessment, and pharmacological management of gait impairment and spasticity in
      MS and their effects on health-related quality of life (HRQoL) are discussed. The
      roles of oral and intrathecal baclofen and of delta-9
      tetrahydrocannabinol/cannabidiol (THC:CBD) oromucosal spray in treating MS
      spasticity-related gait impairment are reviewed. Expert commentary: Mobility
      impairment and spasticity are experienced by approximately 90% and 80% of MS
      patients, respectively, during the disease course. Prevalence and severity of
      gait impairment and spasticity increase as disease progresses. The symptoms are
      related and both impact negatively on HRQoL. Oral baclofen and tizanidine are
      generally used for first-line treatment of MS spasticity but are ineffective in
      approximately 40% of cases. Second-line therapy includes add-on THC:CBD spray for
      patients with resistant MS spasticity. Results of studies evaluating baclofen for
      treating MS spasticity gait impairment are equivocal. In studies of patients with
      resistant MS spasticity, THC:CBD spray consistently improved the timed 10-meter
      walk test and significantly improved multiple spatial-temporal and kinematic gait
      parameters. THC:CBD oromucosal spray warrants further investigation as a
      treatment for MS spasticity-related gait impairment.

PMID- 30235966
TI  - Longer stitch interval in the Krackow stitch for tendon graft fixation leads to
      poorer biomechanical property.
AB  - PURPOSE: The purpose of this study was to analyze the effects of different
      intervals between stitch throws on tendon graft fixation with the Krackow stitch.
      METHODS: Forty-four porcine flexor profundus tendons were randomly divided into
      four groups of 11 specimens each. The Krackow stitch with various stitch
      intervals (2.5, 5.0, 7.5, and 10.0 mm) were evaluated, and named the K-2.5, K
      5.0, K-7.5, and K-10.0 groups, respectively. A braided nonabsorbable suture was
      used to complete each suture-tendon construct. All specimens were pretensioned to
      100 N for three cycles, cyclically loaded from 50 to 200 N for 200 cycles, and
      then finally loaded to failure. Elongation after cyclic loading, ultimate load to
      failure, and the mode of failure were recorded. RESULTS: There were significant
      differences in elongation after cyclic loading among the K-2.5 (31% +/- 5%), K
      5.0 (32% +/- 4%), K-7.5 (34% +/- 5%), and K-10.0 (41% +/- 8%) groups ( p =
      0.004); the post hoc analysis showed significantly smaller values in the K-2.5
      and K-5.0 groups than in the K-10.0 group ( p = 0.002 and 0.003, respectively).
      The stitch interval was correlated with elongation after cyclic loading ( r =
      0.52, p < 0.001). Ultimate loads to failure and cross-sectional area were not
      significantly different across the four groups. CONCLUSION: The Krackow stitch
      with stitch intervals of 2.5 and 5.0 mm had significantly smaller elongation
      after cyclic loading than with an interval of 10.0 mm in this porcine
      biomechanical study. The stitch interval was moderately correlated with
      elongation after cyclic loading.

PMID- 30235967
TI  - Direct and indirect evidences of BDNF and NGF as key modulators in depression:
      role of antidepressants treatment.
AB  - PURPOSE: Depression is one of the most prevalent, recurrent and life-threatening
      mental illnesses. However, the precise mechanism underlying the disorder is not
      yet clearly understood. It is therefore, essential to identify the novel
      biomarkers which may help in the development of effective treatment. METHODS: In
      this milieu, the profile of the brain-derived neurotrophic factor (BDNF) and
      nerve growth factor (NGF) were considered as biomarkers in the light of
      pathophysiology of depression and its treatment. RESULTS: Previously, we have
      reported that BDNF level in the postmortem brain of suicide victims was
      significantly lower than those of normal controls. We also found decreased BDNF
      levels in the specific brain regions of the learned helplessness model of
      depression in rat, and was found to increase normal level following chronic
      fluoxetine hydrochloride treatment. NGF is another important member of
      neurotrophin, which is dysregulated in the pathophysiology of depression in some
      models of peripheral nerve damage and stress. The results shown evidences of the
      effect of antidepressants on modulating depression via the NGF in preclinical and
      clinical models of depression, but conflicted, therefore make it currently
      difficult to affirm the therapeutic role of antidepressants. CONCLUSIONS: Here,
      we review some of the preclinical and clinical studies aimed at disclosing the
      role of BDNF and NGF mediated pathophysiological mechanisms of depression and the
      new therapeutic approaches targeting those key molecules. In addition, an
      important link between BDNF, NGF and depression has been discussed in the light
      of current existing knowledge.

PMID- 30235968
TI  - Comparison of virtual visit versus traditional clinic for management of varicose
      veins.
AB  - Introduction The objective of this study is to compare the clinical outcomes of
      patients with varicose veins managed in the telemedicine clinic and traditional
      clinic. Methods Retrospective analysis of all vein procedures in the
      institutional Vascular Quality Initiative Varicose Vein Registry (VQI VVR) was
      performed from January 2015 to August 2017. Patients were divided into two
      groups: Telemedicine versus Traditional Clinic. Comparison data included patient
      demographics, past medical history, clinical outcomes, patient-reported outcomes
      and postoperative complications. Statistical testing included chi-square test for
      categorical variables and student t-test for continuous variables using the SPSS
      statistical software. Results A total of 1034 varicose vein procedures were
      performed during the 31-month study period. There were 75 virtual encounters in
      the Telemedicine Clinic (Group A) and 959 face-to-face encounters in the
      Traditional Clinic (Group B). Most of the demographics characteristics were
      clinically similar in both groups. Comparing Group A and Group B, there were no
      differences in age, sex, race and body mass index. Early 3-month follow up was
      100% in Group A and 90.7% in Group B. Both groups had low complication rates of
      haematoma (1.3% vs 0.3%, p = 0.884), paraesthesia (1.3% vs 0.6%, p = 0.767) and
      recanalisation (1.3% vs 4.0%, p = 0.383) during the early follow up period.
      Discussion Synchronous virtual visits for patient care are feasible for the
      management of chronic venous disease. Patients with varicose veins who choose to
      undergo telemedicine evaluations have similar pre-operative demographics,
      clinical classification and patient outcomes.

PMID- 30235969
TI  - Long-term outcome of first 300 implanted Absorb bioresorbable vascular scaffolds
      in an all-comers Middle East population.
AB  - Objectives To evaluate long-term clinical outcomes of the Absorb bioresorbable
      vascular scaffold (BVS) system (Abbott Vascular) in an all-comers Middle East
      population. Methods This prospective registry study included an initial set of
      patients with coronary lesions treated using Absorb BVS. Patients were followed
      for target vessel failure (TVF) including cardiac death, target vessel myocardial
      infarction (MI), and target lesion revascularization. Results A total of 217
      patients (age, 55 +/- 11 years; male, 169) with 300 treated lesions were included
      (median follow-up, 36 months [range, 26-41 months]; complete follow-up, 201
      patients). Diabetes mellitus and acute coronary syndrome were present in 50% and
      57% of patients, respectively. TVF rate was 32/201 (15.9%), including cardiac
      death in 10 (5%), target vessel MI in 13 (6.5%), and target lesion
      revascularization in 22 patients (10.9%). Definite or probable device thrombosis
      occurred in 11/201 patients (5.5%). TVF was associated with heart failure, worse
      ejection fraction, multi-vessel BVS, multi BVS in lesion, and total BVS length
      >50 mm. Conclusions Long-term outcome following Absorb BVS implantation in a
      population with high prevalence of high-risk and complex patients is acceptable,
      but heart failure, worse ejection fraction, and multi-vessel or long BVS
      implantation were associated with worse outcomes.

PMID- 30235970
TI  - Predictors of response to 4-aminopyridine in chronic canine spinal cord injury.
AB  - 4-Aminopyridine (4AP), a potassium channel antagonist, can improve hind limb
      motor function in dogs with chronic thoracolumbar spinal cord injury (SCI) but
      individual response is variable. We hypothesized that injury characteristics
      would differ between dogs that do and do not respond to 4AP. Our objective was to
      compare clinical, electrodiagnostic, gait and imaging variables between dogs that
      do and do not respond to 4AP to identify predictors of response. Thirty-four dogs
      with permanent deficits after acute thoracolumbar SCI were enrolled. Spasticity,
      motor and sensory evoked potentials (MEPs, SEPs), H-reflex, F-waves, gait scores
      and magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) were
      evaluated at baseline and after 4AP administration. Baseline variables were
      assessed as predictors of response; response was defined as 1-point change in
      open field gait score. Variables were compared pre- and post-4AP to evaluate 4AP
      effects. Fifteen of 33 (45%) dogs were responders, 18/33 (55%) were non
      responders and 1 was eliminated due to adverse event. Pre-H-reflex threshold <
      1.2mA predicted non-response; pre-H-reflex threshold > 1.2mA and Canine
      Spasticity Scale overall score < 7 were predictive of response. All responders
      had trans-lesional connections on DTI. MEPs were more common post-4AP versus pre
      4AP (10 versus 6 dogs) and 4AP decreased H-reflex threshold and increased
      spasticity in responders. 4-Aminopyridine impacts central conduction and motor
      neuron pool excitability in dogs with chronic SCI. Severity of spasticity and H
      reflex threshold might allow prediction of response. Further exploration of
      electrodiagnostic and imaging characteristics might elucidate additional factors
      contributing to response or non-response.

PMID- 30235971
TI  - Local implantation of autologous adipose-derived stem cells increases femoral
      strength and bone density in osteoporotic rats: A randomized controlled animal
      study.
AB  - BACKGROUND: Deficient osteogenic capacity of bone marrow stem cells plays a
      critical role in the pathophysiology of osteoporosis. Adipose-derived stem cells
      (ADSCs) have emerged as a promising source of skeletal progenitor cells. The
      capacity of ADSCs to undergo osteogenic differentiation and induce mineralized
      tissue formation may be beneficial in the treatment of osteoporosis. We question
      whether administration of autologous ADSCs into the proximal femur of
      osteoporotic rats will induce osteogenesis and enhance bone quality and strength.
      MATERIALS AND METHODS: Thirty ovariectomized female rats were randomly assigned
      to one of the two treatment groups: (1) percutanous implantation of autogenous
      ADSCs-seeded scaffold into the proximal femur and (2) percutanous implantation of
      non-seeded scaffold. The contralateral untreated femur served as control. The
      effect of treatment on bone characteristics was assessed at 12-week follow-up by
      micro-computed tomography analysis, mechanical testing, and histological
      analysis. RESULTS: The mean cortical thickness, total bone volume density, and
      bone load to failure in femora injected with autologous ADSCs-seeded scaffold was
      significantly higher compared to femora injected with non-seeded scaffold and
      compared to the untreated control femora ( p < 0.01). Histological examination of
      the injected specimens revealed complete osseo-integration of the scaffolds with
      direct conversion of the ADSCs into osteoblasts and no inflammatory response.
      CONCLUSIONS: Autogenous ADSCs implantation into the proximal femur of rats with
      ovariectomy-related osteoporosis promoted bone regeneration and increased bone
      strength at short-term follow-up. These findings highlight the potential benefit
      of autogenous ADSCs in the treatment of osteoporosis. LEVEL OF EVIDENCE: Level I,
      randomized controlled trial, animal study.

PMID- 30235972
TI  - Disruption of the RNA exosome reveals the hidden face of the malaria parasite
      transcriptome.
AB  - Antisense transcription emerges as a key regulator of important biological
      processes in the human malaria parasite Plasmodium falciparum. RNA-processing
      factors, however, remain poorly characterized in this pathogen. Here, we purified
      the multiprotein RNA exosome complex of malaria parasites by affinity
      chromatography, using HA-tagged PfRrp4 and PfDis3 as the ligands. Seven distinct
      core exosome subunits (PfRrp41, PfMtr3, PfRrp42, PfRrp45, PfRrp4, PfRrp40,
      PfCsl4) and two exoribonuclease proteins PfRrp6 and PfDis3 are identified by mass
      spectrometry. Western blot analysis detects Dis3 and Rrp4 predominantly in the
      cytoplasmic fraction during asexual blood stage development. An inducible gene
      knock out of the PfDis3 subunit reveals the upregulation of structural and coding
      RNA, but the vast majority belongs to antisense RNA. Furthermore, we detect
      numerous types of cryptic unstable transcripts (CUTs) linked to virulence gene
      families including antisense RNA in the rif gene family. Our work highlights the
      limitations of steady-state RNA analysis to predict transcriptional activity and
      link the RNA surveillance machinery directly with post-transcriptional control
      and gene expression in malaria parasites.

PMID- 30235974
TI  - Place, Injury Patterns, and Female-Victim Intimate Partner Homicide.
AB  - Research demonstrates place matters in the study of intimate partner violence
      (IPV) and intimate partner homicide (IPH) with rural women experiencing more
      severe IPV and a higher risk of IPH. In addition, research points to variations
      in injury patterns with intimates characterized by more wounds and facial
      injuries. Little is known whether injury for female IPH victims differs across
      place; however, research suggests that abuse is a product of a larger social
      context. Using data from the National Violent Death Reporting System, results
      indicate that some variations exist based on degree of urbanicity of the county
      in which the IPH occurred.

PMID- 30235976
TI  - Erenumab in the treatment of migraine.
AB  - Migraine is a highly prevalent neurological pain syndrome, and its management is
      limited due to side effects posed by current preventive therapies. Calcitonin
      gene-related peptide (CGRP) plays a crucial role in the pathogenesis of migraine.
      In recent years, research has been dedicated to the development of monoclonal
      antibodies against CGRP and CGRP receptors for the treatment of migraine. This
      review will focus on the first US FDA-approved CGRP-receptor monoclonal antibody
      developed for the prevention of migraine: erenumab. Two Phase II trials (one for
      episodic migraine and one for chronic migraine) and two Phase III trials for
      episodic migraine have been published demonstrating the efficacy and safety of
      erenumab in the prevention of migraine.

PMID- 30235977
TI  - Accessing ART in Malawi while living in South Africa - a thematic analysis of
      qualitative data from undocumented Malawian migrants.
AB  - The majority of international migrants from Malawi to South Africa are
      undocumented, and some of them are on ART. This study explored how these migrants
      manage to access ART. Qualitative data were collected using open-ended questions
      in semi-structured interviews. 23 returned undocumented Malawian migrants from
      South Africa participated in the study. Also, key informant discussions were held
      with three health workers. Data collection took place in April and May 2015 at a
      rural village of Namwera in Mangochi district in southern Malawi. Interviews were
      audio-recorded, transcribed and translated into English for thematic analysis.
      The guardians collected ART from health facilities in Malawi on behalf of the
      migrants. The guardians sent ART through truck and bus drivers to the migrants in
      South Africa. The migrants shared their ART. Others bought ART from the 'street
      pharmacies'. Others accessed ART from South African health facilities through the
      help of their South African friends. There are risks to dispensing ART to the
      migrants who do not themselves present at health facilities. There is value to
      more regular contacts between clients and health service system that is
      compromised by alternative strategies. It is better to deliver ART services in
      South Africa to the undocumented migrants.

PMID- 30235975
TI  - Vacuum-assisted closure versus moist dressings in the treatment of diabetic wound
      ulcers after partial foot amputation: A retrospective analysis in 65 patients.
AB  - PURPOSE: Changes in weight-bearing patterns after partial foot amputations may
      lead to new localized high-pressure points and keratosis due to ulcerations in
      patients with neuropathies and hypovascular limbs. As a result, diabetic foot
      ulcers (DFUs) after partial foot amputations are very complex. The aim of this
      study was to compare the effectiveness of vacuum-assisted closure (VAC) therapy
      with conventional moist wound dressings in the treatment of diabetic wound ulcers
      after partial foot amputations. METHODS: Sixty-five diabetic patients with a DFU,
      who had previously undergone partial foot amputation surgery, were assigned to
      treatment with VAC (group A: 31 patients) or conventional wound moist dressing
      (group B: 34 patients). The final results were considered as failed treatment if
      reamputation was required. Conversely, reaching 90% of wound granulation was
      considered to be a successful endpoint. RESULTS: The average time to reach 90%
      granulation tissue was significantly lower in group A (7.8 +/- 1.2 weeks vs. 11.1
      +/- 1.2 weeks; p < 0.001). However, there was no significant difference regarding
      the reamputation requirements; 38.7% (12 patients) in group A and 41.2% (14
      patients) in group B, ( p = 0.839). CONCLUSION: The results of this study allowed
      us to conclude that VAC therapy system appears to be an effective treatment for
      patients with complex DFUs who had previously undergone partial foot amputation.

PMID- 30235973
TI  - A Tipping Point in Listening Effort: Effects of Linguistic Complexity and Age
      Related Hearing Loss on Sentence Comprehension.
AB  - In recent years, there has been a growing interest in the relationship between
      effort and performance. Early formulations implied that, as the challenge of a
      task increases, individuals will exert more effort, with resultant maintenance of
      stable performance. We report an experiment in which normal-hearing young adults,
      normal-hearing older adults, and older adults with age-related mild-to-moderate
      hearing loss were tested for comprehension of recorded sentences that varied the
      comprehension challenge in two ways. First, sentences were constructed that
      expressed their meaning either with a simpler subject-relative syntactic
      structure or a more computationally demanding object-relative structure. Second,
      for each sentence type, an adjectival phrase was inserted that created either a
      short or long gap in the sentence between the agent performing an action and the
      action being performed. The measurement of pupil dilation as an index of
      processing effort showed effort to increase with task difficulty until a
      difficulty tipping point was reached. Beyond this point, the measurement of pupil
      size revealed a commitment of effort by the two groups of older adults who failed
      to keep pace with task demands as evidenced by reduced comprehension accuracy. We
      take these pupillometry data as revealing a complex relationship between task
      difficulty, effort, and performance that might not otherwise appear from task
      performance alone.

PMID- 30235978
TI  - Increased Mortality Among Renal Transplant Patients With Invasive Pulmonary
      Aspergillus Infection.
AB  - INTRODUCTION:: Renal transplantation is the most effective and preferred definite
      treatment option in patients with end-stage renal disease. Due to long-term
      immunesuppressive treatment, renal transplant recipients become vulnerable to
      opportunistic infections, especially to fungal infections. METHOD:: This was a
      single-center, retrospective observational study of 438 patients who underwent
      renal transplantation between 2010 and 2016. RESULTS:: Thirty-eight renal
      transplant recipients who had lower respiratory tract infection with median age
      of 41.5 years were evaluated for invasive pulmonary aspergillus (IPA). Of these,
      52.6% were female and 84.2% had living donors. Eleven of 38 lower respiratory
      patients were found to have IPA infection, 5 with proven infection. Compared to
      patients who did not have fungal pulmonary infection, patients with invasive
      aspergillus were older and had high fever, galactomannan levels, and leukocyte
      counts. Mortality was also higher in those patients. Having fever at the baseline
      and IPA infection was significantly associated with mortality in univariate
      analysis and remained related in multivariate model after adjustment for age,
      gender, and fever. CONCLUSION:: Invasive pulmonary aspergillus infection is
      highly associated with increased mortality rates in renal transplant patients.
      Fungal pulmonary infections in immune-suppressed patients should be diagnosed and
      treated immediately in order to avoid the life-threatening complications and may
      greatly improve prognosis.

PMID- 30235979
TI  - Self-Efficacy as a Mechanism Linking Daily Stress to Mental Health in Students: A
      Three-Wave Cross-Lagged Study.
AB  - Background and Objectives While stress is generally well established to be
      predictive for different indicators of mental health, little is known about the
      longitudinal effects of daily life stressors and the role of self-evaluation
      factors. We tested whether perceived general self-efficacy is a mediator for the
      association between daily life stressors and psychopathological symptoms as well
      as subjective well-being. Methods Data derived from 2160 Chinese university
      students was assessed at three time points with one-year intervals. We used the
      Brief Daily Stressor Screening, the General Self-Efficacy Scale, the Positive
      Mental Health Scale, and the Depression Anxiety and Stress Scales. Total, direct,
      and indirect effects were estimated using 95% bootstrapped confidence intervals
      and structural equation modeling. Results Latent variable mediation analyses
      showed that daily stressors were associated with increased symptoms of
      depression, anxiety, and stress and with decreased subjective well-being. All
      cross-lagged mediational paths via self-efficacy were significant in predicting
      positive and negative mental health. Conclusions Considering stress of daily life
      as well as including the two dimensions of mental health may be important for
      future research and practice. This study provides novel evidence for mediating
      stress effects by perceived self-efficacy, which should be focused in
      intervention- and prevention-based approaches.

PMID- 30235980
TI  - Non-stick science: Sixty years of research and (in)action on fluorinated
      compounds.
AB  - Understandings of environmental governance both assume and challenge the
      relationship between expert knowledge and corresponding action. We explore this
      interplay by examining the context of knowledge production pertaining to a
      contested class of chemicals. Per-and polyfluorinated alkyl substances (PFASs)
      are widely used industrial compounds containing chemical chains of carbon and
      fluorine that are persistent, bioaccumulative and toxic. Although industry and
      regulatory scientists have studied the exposure and toxicity concerns of these
      compounds for decades, and several contaminated communities have documented
      health concerns as a result of their high levels of exposure, PFAS use remains
      ubiquitous in a large range of consumer and industrial products. Despite this
      significant history of industry knowledge production documenting exposure and
      toxicity concerns, the regulatory approach to PFASs has been limited. This is
      largely due to a regulatory framework that privileges industry incentives for
      rapid market entry and trade secret protection over substantive public health
      protection, creating areas of unseen science, research that is conducted but
      never shared outside of institutional boundaries. In particular, the risks of
      PFASs have been both structurally hidden and unexamined by existing regulatory
      and industry practice. This reveals the uneven pathways that construct issues of
      social and scientific concern.

PMID- 30235981
TI  - Functional evaluation of early tendon transfer for foot drop.
AB  - AIM: Early tendon transfer has shown good outcomes in peripheral nerve injuries
      of upper limb. However, there is lack of knowledge on early tendon transfer for
      peripheral nerve palsy in lower limb. This study has been designed to study the
      functional outcomes of early tendon transfer in the lower limb, particularly for
      foot drop. PATIENTS AND METHODS: We enrolled 30 cases of foot drop due to
      traumatic sciatic/common peroneal nerve (CPN) palsy between September 2012 and
      March 2016. We performed nerve exploration with repair and early tendon transfer
      in all patients. All patients were followed up for a minimum period of 24 months.
      Functional evaluation was carried out using Stanmore assessment questionnaire.
      RESULTS: At the end of 24 months postoperatively, the Stanmore assessment
      questionnaire score showed a significant improvement from a mean preoperative
      score of 17.5 to mean postoperative score of 86.2. All patients were free of
      ankle-foot orthosis (AFO). All patients were subjectively satisfied. Time to
      return to original job was 5.2 months on an average. Ankle dorsiflexion of the
      operated limb was comparable to the normal limb in cases where there was nerve
      recovery. Planovalgus foot, a known complication of this procedure, was noted in
      24 patients. However, it was not disabling to any patient. CONCLUSION: Early
      tendon transfer in CPN palsy/sciatic nerve palsy has a definite place in the
      management of the injured patient. The transfer, if appropriately carried out,
      acts as a helper, an internal splint, a substitute, or perhaps all of the three
      at varying times in the rehabilitative phase of the patient. Dorsiflexor
      clearance in swing phase of locomotion was quickly restored in all patients,
      obviating the need for AFO.

PMID- 30235982
TI  - Gasless Transaxillary Endoscopic Thyroidectomy with Robotic Assistance: A High
      Volume Experience in North America.
AB  - BACKGROUND: Since its introduction nine years ago, gasless transaxillary
      thyroidectomy with robotic assistance (RT) has achieved a relatively limited
      application in North America. This study aimed to assess the outcomes of RT in a
      recent large, diverse North American population. METHODS: Consenting patients
      were selected for the RT approach from November 2010 to July 2015 based on
      patient preference, and their perioperative data were retrospectively reviewed.
      RESULTS: Of 301 robotic thyroidectomies completed in 281 patients, 160 were total
      thyroidectomy and 141 were lobectomy. Women predominated (98.9%), with a mean age
      of 41 years (range 17-74 years) and a mean follow-up of 24 months (range 3-71
      months). The mean body mass index (BMI) was 25.7 kg/m2 (range 17-44 kg/m2).
      However, 33.3% of patients had a BMI 25-29.9 kg/m2, 12.4% had a BMI 30-34.9
      kg/m2, 3.5% had a BMI 35-39.9 kg/m2, and 0.7% had a BMI >=40 kg/m2. Excluding 20
      completion lobectomy, the indications for surgery were indeterminate cytology
      (53%), malignant cytology (10%), growth (18%), Graves' disease (12%), and other
      (5%). The mean size of the largest resected nodule was 2.5 cm (range 0.7-6.4 cm).
      Mean operating time for robotic lobectomy and total thyroidectomy was 81 and 109
      minutes, respectively. One patient was converted to standard cervicotomy for
      failure to progress endoscopically. Complications included temporary dysphonia
      (6.0%), permanent recurrent laryngeal nerve deficit (1.3%), hypocalcemia
      (temporary 8.2%, permanent 1.1%), seroma (0.7%), and hematoma requiring
      reoperation (0.3%). Complications did not differ in patients with a BMI >=25
      kg/m2 compared to those with a BMI <25 kg/m2 or with respect to nodules >3 cm or
      surgery for Graves' thyroiditis. One patient developed grade II arm lymphedema
      ipsilateral to the axillary incision at two years, which resolved with
      conservative management. No patient had a surgical site infection or brachial
      plexopathy. Cancer was present histologically in 133 (48%) patients. Among 91
      patients with cancer of the index nodule, 48.4% had papillary, 44.0% follicular
      variant papillary, 2.2% minimally invasive follicular carcinoma, and 5.5%
      minimally invasive Hurthle cell carcinoma. One patient had sclerosing variant
      thyroid paraganglioma. To date, all patients are without evidence of tumor
      recurrence. CONCLUSIONS: At a high-volume center, gasless transaxillary
      endoscopic thyroid surgery done with robotic assistance is a safe, efficient, and
      effective approach in a diverse North American patient population.

PMID- 30235983
TI  - Congenital pseudoarthrosis of the clavicle: Should we reconsider timing and
      fixation method?
AB  - BACKGROUND: Congenital pseudoarthrosis of the clavicle (CPC) is rare and may
      require treatment, usually because of an unacceptable appearance or occasionally
      because of pain in an adolescent patient. Spontaneous union is unknown, and
      consequently any desired union requires open reduction and bone grafting. Many
      authors recommend performing the operation at the age of 3-5 years and using
      different fixation methods. We present our experience with three cases and
      literature review in an attempt to further elucidate the appropriate timing of
      the procedure and the fixation method. METHODS: This was a retrospective review
      of three cases presenting with pseudoarthrosis of the clavicle. All cases were
      treated by curettage of the pseudoarthrosis, with the void filled using full
      thickness ileac crest autologous bone graft and bridging plate-one compression
      and two anatomical, at different ages. We performed a literature review with
      emphasis on timing of the procedure, fixation method and complications. RESULTS:
      All patients healed with good callus formation. One patient (5-year-old female
      treated using a compression plate) experienced overlying skin irritation and
      underwent removal of the plate. There were no restriction of movement, pain or
      any other complaint on the final follow-up. We did not find any difference in the
      operating complexity at different ages, but when a compression plate was used, it
      had to be removed later due to bulging of the plate. DISCUSSION: No clinical
      difference was observed between earlier and late operation. Therefore, we suggest
      performing a curettage of the pseudoarthrosis, gapping the void using autologous
      bone graft, and using an anatomical bridging plate.

PMID- 30235984
TI  - In vivo comparison of a fixed loop (EndoButton CL) with an adjustable loop
      (TightRope RT) device for femoral fixation of the graft in ACL reconstruction: A
      prospective randomized study and a literature review.
AB  - INTRODUCTION: There is a lack of in vivo studies comparing the functional outcome
      and knee stability after anterior cruciate ligament reconstruction (ACLR) using
      fixed loop (EndoButton (EB) CL) and adjustable loop (TightRope (TR) RT) devices
      for femoral fixation of soft tissue grafts. MATERIALS AND METHODS: Functional
      outcomes were assessed in terms of the International Knee Documentation Committee
      (IKDC) and Lysholm scores, knee stability by anteroposterior laxity and side-to
      side difference (SSD) using KT-1000 arthrometer. The evaluation was performed
      preoperatively and post-operatively at 6 months and 2 years. RESULTS: Both groups
      were matched in terms of demographic, preoperative, intraoperative and post
      operative covariates. EB ( n = 52) appeared to have better IKDC and Lysholm
      scores at 6 months post-operative when compared to TR ( n = 50). However, at a
      final follow-up of 2 years, the results were similar. The anterior tibial
      translation and SSD were statistically insignificant between the two groups at 6
      months and 2 years. CONCLUSION: ACLR using EB or TR for femoral fixation gives
      substantially equivalent functional results and knee stability at mid-term follow
      up.

PMID- 30235985
TI  - Global nursing as visualised on the internet: a netnographic analysis of the
      emerging global paradigm in nursing.
AB  - BACKGROUND: Positioned to face increasing issues relating to the growing and
      aging population, ill health, climate change, natural disasters, and humanitarian
      crises, nurses play a crucial role in responding to the challenges of
      globalisation. With nurses rising to meet these challenges, the term 'global
      nursing' has been coined. Given the ongoing proliferation of the term, it seems
      relevant to explore the key relationship of the concepts of 'global' and
      'nursing' within the milieus provided through the internet. AIM: To describe how
      global nursing as a concept is visualised in images on the internet. METHOD: A
      cross-sectional observational design based on netnographic methodology was
      conducted. By searching the term 'global nursing' in the Google search engine, a
      total of 973 images illustrating 'global nursing' were collected and stored on
      one specific search occasion. The inclusion of data covered all regions but no
      other search limits. RESULTS: The results show that global nursing, first and
      foremost, is visualised as an academic discourse, as a nursing activity, and as
      an approach to target sustainability. Further, the results also highlight that
      global nursing has manifested as a Western discourse, targeting students with
      access to resources and a humanitarian interest. CONCLUSION: By paying attention
      to global nursing as it is presented in this study, it has been possible to
      provide valuable insights about colonial boundaries in the nursing discourse
      relating to globality. Based on these results, we stress that the nursing
      paradigm would benefit from a greater postcolonial awareness and some reflexivity
      connected with the global issues that nurses are facing. Impact statement: Global
      nursing is paradoxically visualised as something distant, connected to ideas of
      'otherness', and of not belonging to the Western nursing community.

PMID- 30235986
TI  - Distribution of Viral Antigen and Inflammatory Lesions in the Central Nervous
      System of Cockatiels ( Nymphicus hollandicus) Experimentally Infected with Parrot
      Bornavirus 2.
AB  - Neurotropism is a striking characteristic of bornaviruses, including parrot
      bornavirus 2 (PaBV-2). Our study evaluated the distribution of inflammatory foci
      and viral nucleoprotein (N) antigen in the brain and spinal cord of 27 cockatiels
      ( Nymphicus hollandicus) following experimental infection with PaBV-2 by
      injection into the pectoral muscle. Tissue samples were taken at 12 timepoints
      between 5 and 114 days post-inoculation (dpi). Each experimental group had
      approximately 3 cockatiels per group and usually 1 negative control.
      Immunolabeling was first observed within the ventral horns of the thoracic spinal
      cord at 20 dpi and in the brain (thalamic nuclei and hindbrain) at 25 dpi. Both
      inflammation and viral antigen were restricted to the central core of the brain
      until 40 dpi. The virus then spread quickly at 60 dpi to both gray and white
      matter of all analyzed sections of the central nervous system (CNS). Encephalitis
      was most severe in the thalamus and hindbrain, while myelitis was most prominent
      in the gray matter and equally distributed in the cervical, thoracic, and
      lumbosacral spinal cord. Our results demonstrate a caudal to rostral spread of
      virus in the CNS following experimental inoculation of PABV-2 into the pectoral
      muscle, with the presence of viral antigen and inflammatory lesions first in the
      spinal cord and progressing to the brain.

PMID- 30235987
TI  - Irish voters repealed the eighth: now it's time to ensure access to abortion care
      in law and in practice.
AB  - This commentary discusses Ireland's 25 May 2018 Referendum result to repeal the
      Eighth Amendment and has two key aims. Firstly, it encourages policy-makers to
      grasp the full potential of legislative reform by enabling and protecting women's
      access to abortion care within a continuum of sexual and reproductive healthcare
      options. Secondly, it calls for urgent clarity about access to abortion care in
      the interim period of legislative transition.

PMID- 30235988
TI  - Pathological Interactions Between Mutant Thyroid Hormone Receptors and
      Corepressors and Their Modulation by a Thyroid Hormone Analogue with Therapeutic
      Potential.
AB  - BACKGROUND: Thyroid hormone receptors (TRs) are tightly regulated by the
      corepressors nuclear receptor corepressor (NCoR) and silencing mediator of
      retinoic acid and thyroid hormone receptors. Three conserved corepressor/NR
      signature box motifs (CoRNR1-3) forming the nuclear receptor interaction domain
      have been identified in these corepressors. Whereas TRs regulate multiple normal
      physiological and developmental pathways, mutations in TRs can result in
      endocrine diseases and be associated with cancers due to impairment of
      corepressor release. Three mutants that are located in helix H11 of TRs are of
      special interest: TRalpha-M388I, a mutant associated with the development of
      renal clear cell carcinomas (RCCCs), and TRbeta-Delta430 and TRbeta-Delta432, two
      deletion mutants causing resistance to thyroid hormone syndrome. METHODS: Several
      cell-based and biophysical methods were used to measure the affinity between wild
      type and mutant TRalpha and TRbeta and all the CoRNR motifs from corepressors to
      quantify the effects of different thyroid hormone analogues on these
      interactions. This study was coupled with the measurement of interactions between
      wild-type and mutant TRs in the context of a heterodimer with RXR to a NCoR
      fragment in the presence of the same ligands. Structural insights into the
      binding mode of corepressors to TRs were assessed in parallel by nuclear magnetic
      resonance spectroscopy. RESULTS: The study shows that TRs interact more avidly
      with the silencing mediator of retinoic acid and thyroid hormone receptors than
      with NCoR peptides, and that TRalpha binds most avidly to S-CoRNR3, whereas
      TRbeta binds preferentially to S-CoRNR2. In the studied TR mutants, a transfer of
      the CoRNR-specificity toward CoRNR1 was observed, coupled with a significant
      increase in the binding strength. In contrast to 3,5,3'-triiodothyronine (T3),
      the agonist TRIAC and the antagonist NH-3 were very efficient at dissociating the
      abnormally strong interactions between mutant TRbetas and corepressors. A strong
      impairment of T3-binding for TRbeta mutants was shown compared to TRIAC and NH-3
      and could explain the different efficiencies of the different ligands in
      releasing corepressors from the studied TRbeta mutants. Consequently, TRIAC was
      found to be more effective than T3 in facilitating coactivator recruitment and
      decreasing the dominant activity of TRbeta-Delta430. CONCLUSION: This study helps
      to clarify the specific interaction surfaces involved in the pathologic phenotype
      of TR mutants and demonstrates that TRIAC is a potential therapeutic agent for
      patients suffering from resistance to thyroid hormone syndromes.

PMID- 30235989
TI  - Why "Therapeutic Innovation and Regulatory Science".

PMID- 30235990
TI  - ICH Culture: Its Maintenance and Development.
AB  - The founding industry members (European Federation of Pharmaceutical Industries
      and Associations [EFPIA], Japanese Pharmaceutical Manufacturers Association
      [JPMA], and Pharmaceutical Research and Manufacturers of America [PhRMA]) of the
      International Council for Harmonisation (ICH) have a 25-year track record of the
      contribution to ICH. Given that further globalization of ICH is expected, we
      should value this legacy and maintain the current ICH culture and its principles
      of "benefit to the patients first" and "science-based approach," through which
      industry members would ensure transparency and objectivity in their ICH
      activities. In order to maintain and develop the culture of the ICH and its
      current momentum, a 2-way approach is important: (1) sharing common views through
      dialogues among leaders of each industry association, such as through the
      Industry Executive Council, and (2) spreading the values through grassroots
      activities involving wider stakeholders in global forums such as DIA, as
      platforms for sharing the knowledge, views, and culture of ICH across the globe.

PMID- 30235991
TI  - Addressing Challenges and Opportunities of "Less Well-Understood" Adaptive
      Designs.
AB  - The draft adaptive design guidance released by FDA in 2010 included references to
      adaptive study designs that were described as "less well-understood." At that
      time, there was relatively little regulatory experience with such designs, and
      their properties were felt to be insufficiently understood. In order to promote
      greater use of adaptive designs, especially those categorized as less well
      understood, the Best Practice Subteam of the DIA Adaptive Designs Scientific
      Working Group (ADSWG) has worked on describing and characterizing these designs,
      identifying challenges associated with them and suggesting improvements to design
      or study conduct aspects that might make them more acceptable. This paper
      summarizes the work from the subteam.

PMID- 30235992
TI  - Social Media Monitoring and Adverse Drug Reaction Reporting in Pharmacovigilance:
      An Overview of the Regulatory Landscape.
AB  - In the context of the European Union's Innovative Medicines Initiative (IMI)
      project titled Web-Recognizing Adverse Drug Reactions (WEB-RADR; http://web
      radr.eu ), which focuses on the assessment of new data sources and the
      optimization of the collection of information on suspected adverse reactions in
      pharmacovigilance, a survey was performed in 182 countries/jurisdictions in 2014
      to 2015. The goal was to gather information on existing practices, guidance, and
      legal requirements on social media monitoring to identify potential safety issues
      related to medicines. The survey response rate was 100%. The results revealed
      that 80% of the surveyed countries do not have such necessities despite the fact
      that 63% of these countries have an established national pharmacovigilance
      system. Among the countries having an established pharmacovigilance system, only
      29% have specific requirements, most countries do have similar provisions as set
      out in the EU guidelines on Good Pharmacovigilance Practices (GVP). A small
      subset of countries within the European Economic Area (EEA) have requirements
      that exceed those stated in GVP, namely, Italy, France, Sweden, and the UK.
      Outside the EEA, Turkey and the United States have also developed further
      guidance. The outcome of the survey will inform the development of a future
      policy framework on the further use of social media as new pharmacovigilance data
      source in the EEA. In addition, this paper elaborates on some current practical
      case management issues encountered by companies based on the existing regulatory
      guidance.

PMID- 30235994
TI  - Patient Evaluation of Medication Package Leaflets in Al Kharj City, Saudi Arabia.
AB  - OBJECTIVE: The purpose of this study was to determine how well patients could
      correctly recognize and comprehend the various information items in over-the
      counter (OTC) medications package leaflets in Saudi Arabia. METHODS: Leaflets
      from 20 most commonly sold OTC medications were examined by experts to evaluate
      the leaflet layout, language, and content. The same leaflets were also evaluated
      by patients who had their medicines dispensed at 2 hospitals and 8 community
      pharmacies in Al Kharj, Saudi Arabia. A questionnaire was used for the patients'
      examination. RESULTS: A total of 479 questionnaires were included in the study.
      Each package leaflet was examined by at least 20 participants. The results
      indicate poor comprehensibility, for many items, particularly items regarding
      "drug interactions" and "contraindications." CONCLUSION: The participants had
      some difficulty recognizing and comprehending certain information items in the
      package leaflets that are supplied with OTC medications in Saudi Arabia.

PMID- 30235993
TI  - Can Pharmacovigilance Learn From the Oil and Gas Industry, Which Has Been
      Outsourcing for Over a Century?
AB  - Outsourcing in pharmacovigilance has grown in the past decade. However, standards
      are lacking in this area, both for initiating as well as maintaining an outsource
      relationship. In this paper, the authors propose that the sector can learn from
      other industries that have been outsourcing activities for a much longer time,
      such as the oil and gas industry. The Safety Case is put forward as a body of
      evidence that facilitates the continuous exchange of data, especially focused on
      risk management of the relationship between outsourcer and vendor. Finally, the
      authors will make an attempt to come to a global consensus in this area through
      the Allliance for Clinical Research Excellence and Safety (ACRES) network.

PMID- 30235995
TI  - Patient Access in Restrictive Risk Management Programs: The Case of iPLEDGE.
AB  - BACKGROUND: The isotretinoin risk management program iPLEDGE places requirements
      on patients and providers to ensure that the benefits of isotretinoin therapy
      outweigh the risks. Such burdens have the possibility of limiting patient access
      through mechanisms such as lowered physician participation. METHODS: In this
      study, we utilized prescription claims data to examine changes in patient and
      provider participation in isotretinoin therapy with iPLEDGE implementation. We
      examined the change in utilization among patients not targeted by iPLEDGE (male
      patients) to assess the program's impact on access. We also examined whether
      provider participation in isotretinoin therapy varies by specialty and
      isotretinoin prescribing history. RESULTS: Patient access to isotretinoin
      decreased in the period immediately following iPLEDGE implementation, but
      recovered to pre-iPLEDGE levels in the succeeding months. In addition, therapy
      completion rates increased with iPLEDGE implementation, suggesting that patients
      less committed to isotretinoin therapy may be self-selecting out of therapy.
      Lastly, iPLEDGE resulted in decreased participation by low-volume, general
      practitioners, while high-volume, specialists' participation was largely
      unchanged. CONCLUSION: We found that participants responded to iPLEDGE's burdens
      in predictable ways. Insufficient anticipation of potential iPLEDGE rollout
      issues initially disrupted patient treatment and resulted in far fewer patients
      starting therapy. Over a longer term, isotretinoin utilization and therapy
      completion increased and isotretinoin prescribing shifted toward high-volume,
      specialist providers. We argue that these changes are predictable based on the
      burdens iPLEDGE imposes on patients and prescribers and may not be inconsistent
      with the goals of the risk management program.

PMID- 30235996
TI  - Analysis of Fixed-Dose Combination Products Approved by the US Food and Drug
      Administration, 2010-2015: Implications for Designing a Regulatory Shortcut to
      New Drug Application.
AB  - BACKGROUND: Fixed-dose combination (FDC) drugs have been an attractive product in
      pharmaceutical markets because of their unique advantages, but general guidance
      directing the clinical development of FDC drugs is not yet available in the US.
      METHOD: All drug approval reports of FDC products approved by the US FDA from
      January 2010 to December 2015 were intensively analyzed to investigate the
      regulatory requirements of the US FDA. RESULT: Through analyzing 63 approved FDCs
      out of 655 New Drug Application (NDA) approvals, it was found that completion of
      the full phases of clinical trials was not always required for approval by the
      FDA, which indicates that some phases of clinical studies can be possibly
      exempted, if justified. CONCLUSION: The results imply that pharmaceutical
      companies can accelerate FDC development and enter the market earlier if
      scientific regulatory rationales are established.

PMID- 30235997
TI  - DIA's Adaptive Design Scientific Working Group (ADSWG): Best Practices Case
      Studies for "Less Well-understood" Adaptive Designs.
AB  - Adaptive design (AD) clinical trials use accumulating subject data to modify the
      parameters of the design of an ongoing study, without compromising the validity
      and integrity of the study. The 2010 US Food and Drug Administration (FDA) Draft
      Guidance on Adaptive Design Clinical Trials described a subset of 7 primary
      design types as "less well-understood." FDA defined these designs as those with
      limited regulatory experience. To better understand the properties of these less
      well-understood ADs and to promote their use when applicable, the Best Practices
      Subteam for DIA's Adaptive Design Scientific Working Group conducted an extensive
      nonsystematic search and reviewed trials from multiple sponsors who had employed
      these designs. Here, we review 10 specific case studies for which less well
      understood ADs were employed and share feedback about their challenges and
      successes, as well as details about the regulatory interactions from these
      trials. We learned that these designs and associated statistical methodologies
      can make difficult research situations more amenable for study and, therefore,
      are needed in our toolbox. While they can be used to study many diseases, they
      are particularly valuable for rare diseases, small populations, studies involving
      terminal illnesses, and vaccine trials, in which it is important to find
      efficient ways to bring effective treatments to market more rapidly. It is
      imperative, however, that these methodologies be utilized appropriately, which
      requires careful planning and precise operational execution.

PMID- 30235998
TI  - The Current Status of Sakigake Designation in Japan, PRIME in the European Union,
      and Breakthrough Therapy Designation in the United States.
AB  - Following the Breakthrough Therapy Designation system in 2012 in the United
      States, the Sakigake Designation was introduced in 2015 in Japan, and PRIME
      (PRIority MEdicines) was started in 2016 in the European Union. Each system aims
      at giving patients better access to innovative drugs and regenerative medicine
      products by providing product developers with generous regulatory and scientific
      support from an early development stage. So far, the designation systems have
      operated independently in each region, and no products with the same indication
      have been designated commonly under the 3 designation systems. However, no
      designation system excludes a product designated under another system, which
      allows the possibility of an applicant to seek all 3 designations; this may
      happen in the near future. Therefore, an understanding of the current situation
      under each designation system will contribute to effective operation of each
      system as well as identification of further collaborative activities between the
      European Medicines Agency; Japan's Ministry of Health, Labour and
      Welfare/Pharmaceuticals and Medical Devices Agency; and the United States Food
      and Drug Administration. Such collaborations can be successful because these
      organizations have already established a close relationship through international
      activities such as the International Council for Harmonisation of Technical
      Requirements for Pharmaceuticals for Human Use (ICH) and the International
      Coalition of Medicines Regulatory Authorities (ICMRA).

PMID- 30235999
TI  - FDA's Expedited Programs and Their Impact on the Availability of New Therapies.
AB  - The US Food and Drug Administration's (FDA's) Priority Review, Accelerated
      Approval, Fast Track, and Breakthrough Therapy programs have been successful in
      facilitating the drug approval process and getting medications to patients
      quicker. To qualify for one or more of these FDA programs, a sponsor must meet
      specific criteria. Once a drug is given one or more designations, benefits can
      range from frequent meetings with FDA representatives to appointed FDA senior
      managers to facilitate the approval process. This paper will review the major
      guidelines set forth by the FDA, highlight advantages to the patient and health
      care community as a result of receiving specific designations, and provide
      several examples for illustration. As a result of these designations, many
      patients with rare diseases or life-threatening conditions have been afforded
      earlier access to effective therapies. As the pharmacist's role continues to
      expand, it is crucial to understand the nature of these accelerated programs and
      to advocate for increased access to new drug therapies.

PMID- 30236000
TI  - Analysis of the Utilization Status of Essential Medicines in Beijing's Community
      Health Institutions.
AB  - OBJECTIVE: To evaluate essential medicines utilization in community health
      institutions to identify problems hindering the implementation of the Essential
      Medicine System at community level in Beijing, China. METHODS: A total of 20
      community health centers in Beijing were surveyed during September 2014 regarding
      stocking situation and utilization status of essential medicines. Opinions about
      essential medicines utilization were solicited from clinical staff at these
      centers. Average outpatient health expenditure was obtained from the Beijing
      Municipal Health Bureau to evaluate the financial impact. RESULTS: During our
      study, an average of 377 species of essential medicines was stocked by the
      community health institutions, accounting for 53.9% of Beijing Essential Medicine
      List, and 61.6% of the total medicines in the institutions. First-aid and low
      price essential medicines were frequently out of stock. The average expense per
      outpatient visit increased yearly from 2009 to 2013. Feedback from clinical staff
      revealed patients' negative perception of the essential medicines and major
      concerns about its quality. CONCLUSIONS: Our study found both the list and supply
      of essential medicines could not meet the clinical needs of patients at community
      health centers adequately. Furthermore, some existing drug policies had
      restricted the service capacity, thus affecting the centers' function and
      bringing additional negative impact on essential medicines utilization.
      Financially, the inadequacy of essential medicine to meet clinical need and poor
      supply of many low-price drugs contributed much to the rise of average drug
      expenses, limiting the role of essential medicines to improve the quality of care
      at the community level.

PMID- 30236001
TI  - Developing a Practical Method for Validation of Computerized Systems Integrated
      With Smart and/or Wearable Devices for Regulatory Compliance of Clinical Trials.
AB  - BACKGROUND: The use of smart and/or wearable devices for collection of electronic
      data in clinical trials has recently become a strong tool with which to collect
      patients' data in a timely manner. Electronic collection of patient data will
      necessitate comprehensive data analysis involving huge-scale datasets in the
      future. However, it is still unclear how to validate and qualify computerized
      systems used to collect and/or manage electronic clinical data when smart and/or
      wearable devices are involved. METHODS: We (a special interest group of Good
      Automated Manufacturing Practice Japan Forum [GAMP Japan]) investigated and
      designed a data-flow model for a clinical data management system involving smart
      and/or wearable devices, and suggested an approach for the validation of such a
      computerized system. The appropriateness of applying GAMP5 to the validation of a
      clinical data management system involving smart and/or wearable devices was also
      reviewed. RESULTS: A regulated company should have policies and standard
      procedures for validating computerized systems in clinical systems. When a
      sponsor engages a contract research organization (CRO) for clinical data
      management, the sponsor should assess the CRO to confirm their capabilities. The
      sponsor also needs to check whether the CRO assesses device manufacturers as sub
      suppliers. When the CRO intends to conduct sub-supplier assessment with a device
      manufacturer, a risk-based approach can be taken. CONCLUSIONS: We believe our
      method of system validation will be applicable to and will facilitate various
      clinical trials that involve smart and/or wearable devices.

PMID- 30236002
TI  - An Update on the Registration of Biosimilars in Malaysia.
AB  - BACKGROUND: Because of its structure and complex manufacturing process, every
      biotherapeutic product (BTP; medicinal products made by or derived from living
      organisms and produced by biotechnology) adheres to stringent quality assurance
      and control requirements, in addition to extensive nonclinical and clinical study
      data. Similarly, copy products of original biotherapeutics (termed as
      "biosimilars") are subjected to equally strict regulatory control. BTPs have been
      registered in Malaysia since the 1990s; however, registration of biosimilars
      started only in 2008. METHODS: This research aims to compare evaluation practice
      on biosimilar and novel BTPs at the Biological Product Registration Section in
      Malaysia. Evaluation activities were studied in terms of evaluation questions,
      evaluation timeline, nonclinical and clinical requirements, and local
      requirements on product label (including package insert). Six biosimilar product
      dossiers and 6 novel BTP dossiers evaluated in 2013-2015 were sampled. Parameters
      for comparison were determined and analyzed using data collection forms. Specific
      to the biosimilar products, the evaluation practice on labels and package inserts
      were dissected and described in a qualitative arm of this research. RESULTS:
      Generally, the registration requirements of novel BTPs and biosimilar products
      are in agreement with international regulatory practices. However, some labeling
      and package insert requirements, and registration conditions are unique to the
      Malaysian regulatory context. CONCLUSIONS: Study findings revealed some
      similarities and differences in current evaluation practice (timeline and
      requirements) for biosimilar versus novel BTPs. The findings of this research
      also provide an insight on current evaluation practice on biosimilar product
      labeling.

PMID- 30236003
TI  - Current Practices in Choosing Estimands and Sensitivity Analyses in Clinical
      Trials: Results of the ICH E9 Survey.
AB  - BACKGROUND: An addendum to the International Conference on Harmonisation E9 (ICH
      E9) guidance document (Statistical Principles for Clinical Trials) is currently
      under development. The aim of the addendum is to promote harmonized standards on
      the choice of estimand (a well-defined measure of the treatment effect that is
      being estimated) in clinical trials and to describe a consensual framework for
      planning, conducting, and interpreting sensitivity analyses of clinical trial
      data. METHODS: In order to help understand current practices relating to the
      choice of estimands and sensitivity analyses for clinical trials, the ICH E9
      working group developing the addendum conducted a survey with a primary focus on
      clinical trials involving drugs, vaccines, and biologics. The survey was
      distributed electronically between May 19, 2015, and June 11, 2015, to various
      stakeholder groups within ICH, including industry, regulatory, and academic
      communities. A total of 1305 respondents participated. RESULTS: Of the 1305
      respondents 547 (42%), 344 (26%) and 283 (22%) were from Europe, USA and Japan
      respectively. Over half of the respondents work in pharmaceutical companies, and
      approximately a quarter of respondents noted oncology as the primary therapeutic
      area they work in. Over half of the respondents (595, 55%) noted the treatment
      effect being estimated was 'in the entire target population of patients
      regardless of whether they will take treatment as instructed'. The most common
      methods for handling missing data in primary analyses were mixed-models repeated
      measures (555, 56% respondents) and last observation carried forward (549, 55%
      respondents). The majority of respondents (816, 83%) noted they conducted
      sensitivity analyses to estimate treatment effects in different ways compared to
      the primary analysis by using alternative assumptions (627, 78%) and/or using
      alternative statistical methods (616, 76%). CONCLUSIONS: The survey results have
      provided useful information to the ICH E9 working group on current practices on
      the choice of primary estimands for measuring treatment effects in confirmatory
      clinical trials, and approaches used to select sensitivity analyses.

PMID- 30236004
TI  - Adjustment for Propensity Score in Nonrandomized Clinical Studies: Comparison of
      Sivelestat Versus Conventional Therapy for Acute Lung Injury in Acute Respiratory
      Distress Syndrome.
AB  - BACKGROUND: To confirm the effectiveness of sivelestat, a clinical trial was
      conducted comparing sivelestat with conventional treatment in an open,
      nonrandomized, multicenter study of patients with systemic inflammatory response
      syndrome (SIRS)-associated acute lung injury. The primary endpoint was ventilator
      free days (VFD). METHODS: This study adopted a "cluster entry" method to control
      for patient selection bias arising from the unblinded and nonrandomized clinical
      trial. Thus, all patients in the same hospital during the same entry period
      entered the same treatment arm, and entry periods did not overlap. In the primary
      analysis of VFD, adjusted mean VFD values were compared between groups using the
      inverse probability of treatment weighted (IPTW) method, based on propensity
      score, for control of confounding factors. RESULTS: There were 374 patients in
      the sivelestat group and 168 in the conventional therapy group. The primary
      analysis confirmed that sivelestat was effective (between-group difference of
      adjusted mean was 3.5 [2-sided 95% confidence interval, 1.3-5.8]; P = .0022).
      CONCLUSIONS: In general, a study where all patients in the same cluster enter the
      same treatment arm has within-cluster correlations, which need to be considered
      in the study analysis. However, in analysis using the IPTW method, it is usual to
      use a robust variance estimator, the sandwich variance estimator, which is
      consistent regardless of whether the specification of within-cluster correlation
      structure is correct. Thus, in the analysis using the IPTW method, it was found
      that it was not necessary to adopt any other adjustment method for within-cluster
      correlation.

PMID- 30236005
TI  - Methodological Extensions of Phase 2 Trial Designs Based on Program-Level
      Considerations: Further Development of a Case Study in Neuropathic Pain.
AB  - BACKGROUND: Traditionally, sample size considerations for Phase 2 (Ph2) trials
      are based on the desired properties of the design and response information from
      the trials. METHODS: This work extends that of Patel et al (2012) to design Ph2
      trials based on program-level optimization (ie, optimizing the entire Ph2/3 trial
      design strategy). It describes a framework to evaluate the impact that several
      Ph2 design features have on the probability of Phase 3 (Ph3) success and the
      expected net present value (eNPV) of the product. These factors include the Ph2
      sample size, decision rules to select Ph3 dose(s) and sample sizes, as well as
      number of Ph3 trials. Using neuropathic pain as an example, simulations
      illustrate the framework and show the benefit of including these factors in the
      overall decision process. Patel et al considered one dose of test drug in each of
      exactly two Ph3 trials. This work extends that to consider 1 or 2 doses in each
      of 2 Ph3 trials and, if needed, 1 or 2 additional Ph3 trials to substantiate the
      usefulness of the second dose. RESULTS: We found that employing a quantitative
      algorithmic strategy to choose 1 or 2 doses for Ph3 based on trial results does
      not substantially alter the eNPV compared to a strategy of always taking 2 doses
      to Ph3, if appropriate. Similar to the findings by Patel et al, for 1 Ph3 dose,
      we found that Ph2 sample size can be optimized at small to modest sizes when
      allowing for the possibility of taking 2 doses to Ph3. We found that choice of
      number of Ph2 doses depends on the magnitudes and shapes of the true underlying
      efficacy and safety dose-response curves. CONCLUSION: Simulating a sequence of
      clinical trials can inform trial design and drug development strategy.

PMID- 30236006
TI  - DIA Japan Meeting: Thoughts on Global Collaboration.

PMID- 30236007
TI  - Innovation of Medical Products: The Evolution of Regulatory Science, Research,
      and Education.
AB  - We present a commentary on the international aspects of the evolution of
      regulatory science as a multidisciplinary, multistakeholder academic discipline
      of education and applied research emphasizing the need for seamless interaction
      between stakeholders such as regulatory authorities, the pharmaceutical industry,
      universities, payers, and patient organizations. Regulatory science is the
      science of developing new tools, standards, and approaches to evaluate the
      efficacy, safety, quality, and performance of medical products in order to assess
      benefit/risk and facilitate a sound and transparent regulatory decision making
      throughout development and life cycle management.

PMID- 30236008
TI  - Practical Considerations for the Use of Clinical Outcome Assessments (COAs) in
      Pediatric Clinical Research: Examples From Pediatric Gastroenterology.
AB  - Clinical outcome assessments (COAs), including patient-reported outcome (PRO)
      measures, are routinely used in drug development and other clinical research
      initiatives to assess the impact of treatment on patient health and well-being.
      The FDA Guidance for Industry Patient-Reported Outcome Measures: Use in Medical
      Product Development to Support Labeling Claims (2009), the European Medicines
      Agency's Reflection Paper on the Regulatory Guidance for the Use of Health
      Related Quality of Life Measures in the Evaluation of Medicinal Products (2005),
      and the International Society for Pharmacoeconomics and Outcomes Research PRO
      Good Research Practices for the Assessment of Children and Adolescence Task Force
      (2013) outline key considerations and good measurement principles that are
      relevant to the selection and use of COAs in a pediatric population. However,
      challenges remain in the appropriate selection and use of COAs to assess
      treatment benefit in pediatric clinical research. The purpose of this paper is to
      summarize proceedings from a panel presentation at the Critical Path Institute's
      2015 Annual PRO Consortium Workshop. This paper underscores the importance of
      considering children's specific needs and the numerous challenges faced when
      developing and implementing well-defined and reliable COAs in pediatric clinical
      trials evaluating medical products, and describes some approaches to addressing
      these unique needs and challenges.

PMID- 30236009
TI  - Incorporation of a Benefit-Risk Assessment Framework Into the Clinical Overview
      of Marketing Authorization Applications.
AB  - BACKGROUND: The main responsibility of regulators and industry is to ensure the
      benefit-risk balance of pharmaceutical products is positive for the intended
      patient populations. In recent decades, regulators and industry have taken steps
      to systematize benefit-risk decision making related to marketing authorization
      applications through the use of structured benefit-risk assessment. METHODS: This
      manuscript presents an outline for a structured benefit-risk assessment that can
      be incorporated into Section 2.5.6 of the Clinical Overview to provide the basis
      for approval of pharmaceutical products in these regulatory submissions. RESULTS:
      The structured format presents the benefits and risks of a pharmaceutical product
      in the context of the medical need in the disease state, the benefits and risks
      of available pharmacologic and nonpharmacologic therapies, and the approach for
      mitigating the risks of the product under review. CONCLUSIONS: Ultimately, such
      an approach that lends further support to quality decision making would be
      beneficial to patients who would be treated with new pharmaceutical products.

PMID- 30236010
TI  - Impact of Premium Rewards for the Promotion of Innovative Drug Discovery on the
      Japanese Pharmaceutical Market: An Analysis by Therapeutic Area.
AB  - BACKGROUND: A new incentive program, "Premium Rewards for the Promotion of
      Innovative Drug Discovery and Resolution of Off-Label Use, etc," was introduced
      in Japan in 2010 and subsequently applied in 2010, 2012, and 2014. In our
      previous study, we reported statistical evidence regarding the attributes of
      drugs for which these premium rewards were used. We found that orphan drugs and
      drugs in certain therapeutic areas, including neuroscience, oncology, and
      immunology, were likely to receive rewards. However, that investigation was not
      conducted to clarify how the rewards system affects pharmaceutical sales or
      whether drugs that received rewards led to more profits for pharmaceutical
      companies. METHODS: The data set for this study was a list of the 500 top-selling
      pharmaceuticals in Japan from 2010 to 2014, which was obtained from the IMS Japan
      Pharmaceutical Market database. To clarify the effect of the rewards system on
      different therapeutic areas, total sales and quantity sold were compared between
      drugs that received rewards and those that did not. RESULTS: The rewards system
      positively affected drug sales in specific therapeutic areas, including those
      with Anatomical Therapeutic Chemical (ATC) classifications neuroscience (N) and
      oncology (L), as well as the quantity sold of neuroscience-related drugs.
      CONCLUSION: Our study suggests that this system has been working according to its
      original aim of promoting the development of innovative drugs in Japan.

PMID- 30236011
TI  - Benefits of Centralized ECG Reading in Clinical Oncology Studies.
AB  - BACKGROUND: Many clinical trials of investigational oncologic agents utilize
      electrocardiogram (ECG) machine measurements of QTc, for inclusion/exclusion and
      dosing decisions, though their reliability in this setting has not been
      established. METHODS: We compared the digital ECG machine QTc measurements with
      those obtained by a centralized ECG core lab on more than 270,000 consecutive
      ECGs collected from 299 clinical oncology trials. RESULTS: The mean difference
      between the ECG machine measurements and the central measured QTcF was 1.8 +/-
      15.7 milliseconds. In addition, 29.7% of ECGs with an ECG machine-measured QTcF
      >450 milliseconds had a centrally measured QTcF <450 milliseconds, 44.6% of ECGs
      with an ECG machine-measured QTcF >470 milliseconds had a centrally measured QTcF
      <470 milliseconds, and 77.2% of ECGs with an ECG machine-measured QTcF >500
      milliseconds had a centrally measured QTcF <500 milliseconds. The likelihood of a
      large discrepancy between the ECG machine- and centrally measured value for QTcF
      increased at both the high and low ends of the range of ECG machine QTcF
      measurements. CONCLUSIONS: While on average ECG machine-measured QTcF values were
      very similar to the central core lab measurements; there were very significant
      discrepancies which will have important implications for patient recruitment for
      clinical oncology trials as well as for patient safety during dosing with new
      oncologic agents. Reliance on ECG machine QTc measurements during clinical
      oncology trials may lead to unnecessary exclusion of patients as well as unneeded
      treatment interruptions.

PMID- 30236012
TI  - Studies of Product Structure Adjustment Routes for China's Pharmaceutical
      Industry: A View From the New Healthcare Reform Targets.
AB  - BACKGROUND: The 12th Five-Year Plan period is a critical period for the
      development of the pharmaceutical industry in China. A major focus coming with
      the New Healthcare Reform is a product structure adjustment in the pharmaceutical
      industry. Many researchers have been attracted in recent years to product
      structure adjustment studies. METHODS: An empirical analysis of resources of the
      New Healthcare Reform was conducted by employing clustering analysis. A panel
      data model was established, with independent variables consisting of the city
      residents' medical insurance fund, drug fees per capita, city medical insurance
      fees per capita, rural medical insurance fees per capita, and number of people
      benefiting from the new rural cooperative medical scheme and the dependent
      variable being China's medical technology advancement fees. This study covered 29
      provinces and regions and used panel data from 2007 to June 2012 to establish a
      fundamental regression equation for quantitative analysis. RESULTS: The city
      residents' medical insurance fund, rural medical insurance fees, and the new
      rural cooperative medical scheme are significant factors for pharmaceutical
      structure adjustment in China. The rural medical services market is the most
      important target market for pharmaceutical industrial transformation. CONCLUSION:
      The fundamental drug system and medical insurance system, which the New
      Healthcare Reform focuses upon, are closely related to the pharmaceutical product
      structure. For entities in which structural adjustment is not autonomous, changes
      can be achieved through sound coordination between organizational structure,
      technical structure, and repeated evaluation of consistency of drug product
      quality and overseas technical license.

PMID- 30236013
TI  - Efficient Source Data Verification Using Statistical Acceptance Sampling: A
      Simulation Study.
AB  - BACKGROUND: One approach to increase the efficiency of clinical trial monitoring
      is to replace 100% source data verification (SDV) by verification of samples of
      source data. An intuitive strategy for determining appropriate sampling plans
      (ie, sample sizes and the maximum tolerable number of transcription errors in the
      samples) is to use acceptance sampling methodology. Expanding upon earlier work
      in which the use of acceptance sampling strategies for sampling-based SDV was
      proposed, we describe an alternative acceptance sampling strategy that, instead
      of relying on sampling standards, evaluates all possible sampling plans
      algorithmically, thereby ensuring that selected sampling plans conform to
      prespecified criteria. METHODS: Empirical trial data guided the design of the
      proposed strategy. In addition, extensive simulations, also based on the
      empirical data, were performed to assess the performance in terms of workload
      reductions and the post-SDV error proportion of applying the proposed strategy.
      RESULTS: 13 different scenarios were simulated, but results of the default
      scenario show that the average pre-SDV error proportion per trial of .056 was
      reduced to .023 by inspecting only 40.5% of the case report form entries. Of the
      inspected data entries, almost half (18.0/40.5) was, on average, SDV-ed as part
      of the sampling process; remaining entries were inspected during full inspections
      after too many errors were observed in the samples. CONCLUSION: Our results
      suggest that major reductions in workload can be achieved, while maintaining
      acceptable data quality levels. However, the results also indicate that the
      proposed strategy is conservative and further improvement is possible.

PMID- 30236014
TI  - Factors That Affect the Acquisition of Reward Premiums for Promotion of
      Innovative Drug Discovery in Japan.
AB  - BACKGROUND: A new reward premium system, "Reward Premiums for the Promotion of
      Innovative Drug Discovery and Resolution of Off-label Use Issue, etc," unique to
      Japan, was introduced in 2010 and was used in 2010, 2012, and 2014. If the new
      rewards system is applied to a drug, the company can recover costs early and
      reinvest in research and development of unapproved or innovative drugs. However,
      a detailed analysis of the drugs to which this new system was applied has not
      been conducted. In this study, a data analysis was performed to determine what
      factors were strongly associated with receiving a reward. METHODS: Domestic
      pharmaceuticals in the top 500 sales in September 2009, 2011, and 2013 were
      selected for this study. Multivariable or univariate logistic regression was
      performed. RESULTS: The following factors were significantly related to receiving
      a reward: a more recent launch, a global promotional company, and orphan drug
      designation. Cardiovascular drugs were less likely to receive rewards, whereas
      drugs acting on the central nervous system, anticancer agents, and
      immunomodulatory agents were significantly more likely to receive rewards.
      CONCLUSIONS: These findings suggest that orphan drugs and drugs with specific
      Anatomical Therapeutic Chemical (ATC) classifications such as N and L are likely
      to receive rewards. We can verify that this incentive program works well in
      Japan, launching truly innovative drugs that meet high medical needs.

PMID- 30236015
TI  - Comparison of Treatment Effects Between US and Non-US Study Sites in
      Multiregional Alzheimer Disease Clinical Trials.
AB  - BACKGROUND: Conducting clinical trials across multiple regions of the world has
      become common practice. A multiregional clinical trial (MRCT) presents
      opportunities as well as challenges. However, regional differences of treatment
      effects appear in many MRCTs, which make the interpretation of clinical trial
      results difficult and presents challenges for clinical trial design. Alzheimer
      disease (AD) is a progressive neurodegenerative disorder that affects
      approximately 5 million people in the United States and is the sixth leading
      cause of death in the country. In 2014, AD cost the United States $214 billion,
      and the cost is expected to rise to $1.2 trillion by 2050. METHODS: In this
      article, we utilize data from New Drug Applications (NDAs) that have been
      approved for the treatment of AD to study whether there are differences in
      treatment effect between US and non-US study sites. Using an analysis of
      covariance (ANCOVA) model and forest plot, we analyze the treatment difference by
      region (US and non-US) from 3 separate perspectives: by region for each trial, by
      region for each endpoint, and by region and trial for each endpoint. RESULTS:
      Overall, the analyses indicate that treatment effects in clinical trials for AD
      are generally in the expected direction in both US and non-US sites. There was no
      clear evidence of heterogeneity in treatment effects between US and non-US sites.
      CONCLUSIONS: It appears that there is no clear evidence to suggest that MRCTs
      should not be used to study AD.

PMID- 30236016
TI  - Interpreting Change in Scores on Patient-Reported Outcome Instruments.
AB  - Interpreting change in scores on patient-reported outcome instruments is a key
      aspect of instrument development. Without interpretation guidelines, the clinical
      meaning of significant improvements observed within a treatment group cannot be
      ascertained. While the field has contemplated this topic for several decades,
      there remains inconsistency in terminology, methods, and application. Careful
      selection of methods can result in determining when change is meaningful, but
      researchers must keep an open mind to the methods that best fit their study and
      instrument. In many cases, anchor-based methods are appropriate, but the
      statistical model that evaluates them should be defensible (eg, linear
      regression, repeated-measures modeling, logistic regression). Sometimes,
      researchers must entertain the use of novel methods that may be more appropriate
      for their planned studies and instrument (eg, standard setting, exit interviews,
      conjoint analysis). The selection of the method is best supported by clear,
      transparent communication with the regulatory agency to ensure that the method
      can support its goals.

PMID- 30236017
TI  - Detecting Data Quality Issues in Clinical Trials: Current Practices and
      Recommendations.
AB  - BACKGROUND: Data quality issues in clinical trials can be caused by a variety of
      behaviors including fraud, misconduct, intentional or unintentional
      noncompliance, and significant carelessness. Regardless of how these behaviors
      are defined, they may compromise the validity of the study results. Reliable
      study results and quality data are needed to evaluate products for marketing
      approval and for decisions that are made on the use of medicine. This article
      focuses on detecting data quality issues, irrespective of origin or motive. Early
      detection of data quality issues are important so that corrective actions taken
      can be implemented during the conduct of the trial, recurrence can be prevented,
      and data quality can be preserved. METHODS: A survey was distributed to
      TransCelerate member companies to assess current strategies for detecting and
      mitigating risks involving fraud and misconduct in clinical trials. A review of
      literature across many industries from 1985 to 2014 was conducted using multiple
      platforms. RESULTS: Eighteen TransCelerate member companies anonymously responded
      to the survey. All of the respondents had one or more existing strategies for
      fraud and misconduct detection. The literature search identified current
      practices and methodologies across many industries. CONCLUSIONS: TransCelerate
      recommends the creation of an integrated, multifaceted approach to proactively
      detect data quality issues. Detection methods should include a strategy tailored
      to the characteristics of the study. Some sponsors are taking advantage of more
      advanced methods and integrated processes and systems to proactively detect and
      address issues, relying on advances in technology to more efficiently review data
      in real time. Further research is underway to assess statistical data quality
      detection methodology in clinical trials.

PMID- 30236018
TI  - Risk Management Plans in the European Union: Nonclinical Aspects.
AB  - Within the European Union (EU) there is a requirement to submit a risk management
      plan (RMP) for a proposed new drug at the time of submission of the Marketing
      Authorisation Application (MAA). An RMP may also be needed for existing products
      when there is a significant change to the MAA. Although regulatory guidance is
      available to help frame what nonclinical data need to be discussed in the RMP,
      there is little information available on what is considered to be appropriate
      content. However, the presentation and discussion of generated nonclinical data,
      and whether any of the study findings pose an actual or potential safety concern
      for human use, forms a vital component of the RMP. To confirm this situation,
      data from centrally authorized products in the EU show that the majority of those
      with a published RMP summary contain information concerning nonclinical aspects
      of development. This article provides information to aid in the decision making
      of appropriate nonclinical content in the RMP and highlights the most common
      nonclinical endpoints discussed in published RMP summaries both as Identified or
      Potential Risks and as Planned Studies to further evaluate the risk.

PMID- 30236019
TI  - Defining a Central Monitoring Capability: Sharing the Experience of TransCelerate
      BioPharma's Approach, Part 2.
AB  - BACKGROUND: TransCelerate's model approach to risk-based monitoring (RBM)
      includes the application of the appropriate monitoring activities to enable both
      the early detection and timely resolution of issues. This article is a follow-up
      to part 1, published in the September 2014 issue with the same title. METHODS:
      The intent of this paper is to share information on what has been learned by
      various companies' applications of central monitoring activities based on
      different RBM operating models. A library of risk indicators has been created,
      and this paper provides additional guidance on what has been learned in the
      application of these tools. RESULTS: The goal is to share the needs related to
      people, process, and technology as experienced by TransCelerate member companies.
      CONCLUSIONS: One of the primary issue detection methods of central monitoring is
      the proactive identification of areas of focus through the use of risk
      indicators.

PMID- 30236020
TI  - Implementation of the European QRD Template in Package Leaflets of Centralized
      Approved Medicines.
AB  - BACKGROUND: Package leaflets of medicines distributed within the European Union
      should use the template headings and standard texts created by the Working Group
      on the Quality Review of Documents (QRD). The following study investigated how
      the QRD template is implemented in this patient information. METHODS: All English
      language package leaflets available on the European Medicines Agency website for
      centralized authorization procedures were downloaded 3 times, separated by a time
      period of 1 year. A catalog of criteria was applied to analyze QRD template text
      use. RESULTS: Because of the rapid implementation of updates, the template text
      used in each package leaflet (N = 565) increased from an average of 444 words in
      the first download to 565 words during the 2 subsequent years. With template
      version 7, the fraction of template text per leaflet was 19.7% in 2011, which
      increased to 21.5% in 2013 with implementation of version 9. CONCLUSIONS:
      Limitation to mandatory contents through stricter use of the QRD template's
      bracketing convention, which would reduce package leaflets' text without loss of
      essential information, is suggested. In addition, making the current QRD template
      more concise is strongly recommended.

PMID- 30236021
TI  - Establishing Equivalence of Electronic Clinician-Reported Outcome Measures.
AB  - BACKGROUND: Electronic administration of clinician-reported outcomes (eClinROs)
      has advantages over paper-based methods, but the mode of administration change
      has the potential to affect the validity of the scale. The literature on
      migration of patient-reported outcomes (PROs) suggests that there are different
      levels of modification, which necessitate different approaches to demonstrating
      mode equivalence. However, little has been written on the migration of ClinROs to
      electronic administration. METHODS: We propose a method of comparing paper and
      electronic versions of scales that includes a comparison based on content and a
      comparison based on format. The determination of whether the eClinRO has
      undergone minor, moderate, or substantial modification will drive the necessary
      studies required for validation. RESULTS: The unique characteristics of ClinROs
      suggest 2 additional types of modifications, including functionality adaptation
      and adaptation of instructions. CONCLUSIONS: In many respects, the migration of a
      ClinRO to electronic administration is similar to that of a PRO. This article has
      explored the ways in which there might be special considerations for ClinROs that
      have not been elaborated for PROs.

PMID- 30236022
TI  - Defining Regions in Multiregional Clinical Trials: An Analytical Approach to
      Considering Impact of Intrinsic and Extrinsic Factors.
AB  - BACKGROUND: This article describes follow-up work extended from Tanaka et al
      (2011) in defining the region in multiregional clinical trials (MRCTs). The
      previous paper advocated a systematic approach to defining regions and
      recommended the sponsor to think through carefully, prespecify, and justify any
      regional definitions as well as obtain regulatory concurrence prior to study
      conduct. Particular attention was advised for intrinsic and extrinsic factors
      such as race/ethnicity, disease epidemiology, medical practice, and geographic
      proximity. An analytical approach such as a cluster method to define region was
      introduced, and references on observed regional differences were provided.
      METHODS: A closer review of those references and others from a more comprehensive
      literature search was conducted to gain a deeper understanding of intrinsic and
      extrinsic factors in relation to the observed regional differences in the
      treatment effect. The application of a k-means cluster method to define region
      was explored, as well as the implication to regional sample size for MRCTs.
      RESULTS: Of extrinsic factors, diagnostic capabilities, medical/clinical practice
      such as aspirin use, patient care such as site's usual practice, intervention,
      capability, and concomitant medications were considered potential contributors to
      differences in clinical outcomes or measures. Commonly reported intrinsic factors
      were underlying etiology, epidemiology, genetics, and patient characteristics
      (age, ethnicity, race, risk factors). CONCLUSION: Using a checklist to identify
      intrinsic/extrinsic factors that might lead to differences in treatment effect
      allows one to scientifically define more meaningful regions from the identified
      factors, which will help with estimating the relative treatment outcome as well
      as exploring appropriate regional sample size.

PMID- 30236023
TI  - Extended Risk-Based Monitoring Model, On-Demand Query-Driven Source Data
      Verification, and Their Economic Impact on Clinical Trial Operations.
AB  - BACKGROUND: Computer-aided data validation enhanced by centralized monitoring
      algorithms is a more powerful tool for data cleaning compared to manual source
      document verification (SDV). This fact led to the growing popularity of risk
      based monitoring (RBM) coupled with reduced SDV and centralized statistical
      surveillance. Since RBM models are new and immature, there is a lack of consensus
      on practical implementation. Existing RBM models' weaknesses include (1) mixing
      data monitoring and site process monitoring (ie, micro vs macro level), making it
      more complex, obscure, and less practical; and (2) artificial separation of RBM
      from data cleaning leading to resource overutilization. The authors view SDV as
      an essential part (and extension) of the data-validation process. METHODS: This
      report offers an efficient and scientifically grounded model for SDV. The
      innovative component of this model is in making SDV ultimately a part of the
      query management process. Cost savings from reduced SDV are estimated using a
      proprietary budget simulation tool with percent cost reductions presented for
      four study sizes in four therapeutic areas. RESULTS: It has been shown that an
      "on-demand" (query-driven) SDV model implemented in clinical trial monitoring
      could result in cost savings from 3% to 14% for smaller studies to 25% to 35% or
      more for large studies. CONCLUSIONS: (1) High-risk sites (identified via
      analytics) do not necessarily require a higher percent SDV. While high-risk sites
      require additional resources to assess and mitigate risks, in many cases these
      resources are likely to be allocated to non-SDV activities such as GCP, training,
      etc. (2) It is not necessary to combine SDV with the GCP compliance monitoring.
      Data validation and query management must be at the heart of SDV as it makes the
      RBM system more effective and efficient. Thus, focusing SDV effort on queries is
      a promising strategy. (3) Study size effect must be considered in designing the
      monitoring plan since the law of diminishing returns dictates focusing SDV on
      "high-value" data points. Relatively lower impact of individual errors on the
      study results leads to realization that larger studies require less data
      cleaning, and most data (including most critical data points) do not require SDV.
      Subsequently, the most significant economy is expected in larger studies.

PMID- 30236024
TI  - Rapid complete remission of metastatic melanoma after first-line treatment with
      nivolumab plus tumor-infiltrating lymphocytes.
AB  - Melanoma is the most common type of skin cancer in both men and women in the USA.
      The standard treatment modality for advanced melanoma is immunotherapy, either
      alone or in combination. As single-agent immunotherapy is usually inadequate,
      combined immunotherapy might be a good choice and combined treatment modalities
      appropriate for melanoma need to be explored. Herein, we report a case of
      metastatic melanoma successfully treated with combined therapy of tumor
      infiltrating lymphocytes and nivolumab. Complete remission was achieved
      approximately 4 months after the initiation of treatment. The treatment was well
      tolerated and only grade 1 fatigue occurred. The patient was still on complete
      remission 1 year after stopping the treatment. Our result showed that this
      treatment modality might be an ideal option for patients with metastatic
      melanoma.

PMID- 30236025
TI  - Long-term safety of alpha-1 antitrypsin therapy in children and adolescents with
      Type 1 diabetes.
AB  - Promising findings of alpha-1 antitrypsin (AAT) intervention in mice models of
      Type 1 diabetes (T1D) led researchers to investigate AAT as a therapeutic
      modality for beta-cell preservation in recent-onset T1D patients. Our
      prospective, open-label Phase I/II extension study demonstrated that the
      administration of multiple repeated AAT infusions (up to 36) to AAT-sufficient
      pediatric T1D patients is safe and well-tolerated. Long-term surveillance of
      participants (up to 5 years) from diabetes onset revealed normal growth and
      pubertal progression through adolescence to attainment of full puberty and near
      adult height. No serious adverse events, clinical or laboratory abnormalities
      were reported. Given its safety profile, AAT may be an individualized-tailored
      innovative immunotherapy in AAT-sufficient pediatric patients with diverse immune
      related medical conditions. ClinicalTrials.gov Identifier: NCT01661192.

PMID- 30236026
TI  - Gold nanoparticles-mediated photothermal therapy and immunotherapy.
AB  - Cancer has been a significant threat to human health with more than eight million
      deaths each year in the world. Therefore, there is a significant need for novel
      technologies to effectively treat cancer and ultimately reduce cancer
      recurrences, treatment costs, number of radical cystectomies and mortality. A
      promising therapeutic platform for cancer is offered by nanoparticle-mediated
      therapy. This review highlights the development and applications of various
      nanoparticle platforms for photo-induced hyperthermia and immunotherapy. Taking
      advantage of gold's high biocompatibility, gold nanoparticles (GNPs) can be
      injected intravenously and accumulate preferentially in cancer cells due to the
      enhanced permeability and retention effect. Various gold nanoplatforms including
      nanospheres, nanoshells, nanorods, nanocages and nanostars have been used for
      effective photothermal treatment of various cancers. GNPs have also been used in
      immunotherapies, involving cancer antigen and immune adjuvant delivery as well as
      combination therapies with photothermal therapy. Among GNPs platforms, gold
      nanostars (GNS) have great therapeutic potential due to their unique star-shaped
      geometry that dramatically enhances light absorption and provides high photon-to
      heat conversion efficiency due to the plasmonic effect. This photothermal process
      can be exploited to specifically ablate tumors and, more importantly, to amplify
      the antitumor immune response following the highly immunogenic thermal death of
      cancer cells. GNS-mediated photothermal therapy combined with checkpoint
      immunotherapy has been found to reverse tumor-mediated immunosuppression, thereby
      leading to the treatment of not only primary tumors but also cancer metastasis,
      as well as to induce effective long-lasting immunity, in other words, an
      anticancer 'vaccine' effect.

PMID- 30236027
TI  - Immunotherapy beyond progression in advanced renal cell carcinoma: a case report
      and review of the literature.
AB  - Immunotherapy is associated with different response patterns compared with
      chemotherapy and targeted therapy, including delayed response and stabilization
      after progression (pseudoprogression). According to new immuno-based response
      criteria, immunotherapy can be continued after radiological progression when a
      clinical benefit is observed. We report a case of an advanced renal cell
      carcinoma patient treated with nivolumab, who developed clinical benefit and
      delayed radiological response after initial progression. We performed a review of
      the literature on immunotherapy beyond progression in advanced solid tumors. 12
      clinical trials were identified and showed that selected patients have subsequent
      response and survival benefit receiving immunotherapy beyond progression. Future
      studies are needed to optimize timing and duration of immunotherapy and to define
      patient selection criteria for treatment beyond progression.

PMID- 30236028
TI  - Letter to the Editor.

PMID- 30236029
TI  - Matrine induces apoptosis via targeting CCR7 and enhances the effect of
      anticancer drugs in non-small cell lung cancer in vitro.
AB  - This study mainly investigated the effects of matrine on cell apoptosis and the
      effects of anticancer drugs in non-small cell lung cancer (NSCLC) cell lines
      (A549 and LK2 cells). The results showed that matrine (>=10 MUM) caused a
      significant inhibition on cell viability and 10 and 100 MUM matrine induced cell
      apoptosis via influencing p53, bax, casp3, and bcl-2 expressions in A549 cells.
      In addition, matrine significantly down-regulated C-C chemokine receptor type 7
      (CCR7) expression, and blocking the down-regulation of CCR7 by exogenous
      chemokine ligand 21 (CCL21) treatment alleviated matrine-caused effects of
      apoptosis genes in A549 cells. The results were further validated in LK2 cells
      that matrine regulated apoptosis gene expressions, which were reversed by CCL21
      treatment. Furthermore, matrine enhances the effects of cisplatin, 5
      fluorouracil, and paclitaxel in A549 cells, and the anticancer effects exhibit a
      dosage-dependent manner. In summary, matrine induced cell apoptosis and enhanced
      the effects of anticancer drugs in NSCLC cells; the mechanism might be associated
      with the CCR7 signal.

PMID- 30236030
TI  - When and how NK cell-induced programmed cell death benefits immunological
      protection against intracellular pathogen infection.
AB  - NK cells are innate lymphoid cells that exert a key role in immune surveillance
      through the recognition and elimination of transformed cells and viral,
      bacterial, and protozoan pathogen-infected cells without prior sensitization.
      Elucidating when and how NK cell-induced intracellular microbial cell death
      functions in the resolution of infection and host inflammation has been an
      important topic of investigation. NK cell activation requires the engagement of
      specific activating, co-stimulatory, and inhibitory receptors which control
      positively and negatively their differentiation, memory, and exhaustion. NK cells
      secrete diverse cytokines, including IFN-gamma, TNF-alpha/beta, CD95/FasL, and
      TRAIL, as well as cytoplasmic cytotoxic granules containing perforin, granulysin,
      and granzymes A and B. Paradoxically, NK cells also kill other immune cells like
      macrophages, dendritic cells, and hyper-activated T cells, thus turning off self
      immune reactions. Here we first provide an overview of NK cell biology, and then
      we describe and discuss the life-death signals that connect the microbial
      pathogen sensors to the inflammasomes and finally to cell death signaling
      pathways. We focus on caspase-mediated cell death by apoptosis and pro
      inflammatory and non-caspase-mediated cell death by necroptosis, as well as
      inflammasome- and caspase-mediated pyroptosis.

PMID- 30236031
TI  - Editor's Note.

PMID- 30236032
TI  - Drinking to Cope Motivations as a Mediator of the Relationship Between Sexual
      Coercion Victimization and Alcohol Use Among College Women: The Role of
      Depressive Symptoms.
AB  - This cross-sectional study examined whether depressive symptoms strengthened the
      relationship between different forms of sexual coercion victimization and
      drinking to cope motivations, which was hypothesized to influence alcohol use.
      Participants were 214 female undergraduates who completed an online survey.
      Participants who experienced any lifetime sexual coercion and reported higher
      depressive symptoms were the most likely to report drinking to cope motivations,
      which in turn were associated with alcohol use. Depressive symptoms did not
      strengthen the relationship between specific forms of sexual coercion, drinking
      to cope, and alcohol use. Increasing emotion regulation strategies among sexual
      coercion victims may reduce drinking.

PMID- 30236033
TI  - A qualitative study exploring views and experiences of people with stroke
      undergoing transcranial direct current stimulation and upper limb robot therapy.
AB  - Background Neurorehabilitation technologies used mainly in research such as robot
      therapy (RT) and transcranial direct current stimulation (tDCS) can promote upper
      limb motor recovery after stroke. Understanding the feasibility and efficacy of
      stroke rehabilitation technologies for upper limb impairments is crucial for
      effective implementation in practice. Small studies have explored views of RT by
      people with stroke; however experiences of people receiving tDCS in combination
      with RT have never been explored. Objective To explore views and experiences of
      people with sub-acute and chronic stroke that had previously taken part in a
      randomised controlled trial involving tDCS and RT for their impaired upper limb.
      Methods An interview study includes open and closed questions. Face-to-face
      interviews were audio recorded. Open-ended question responses were transcribed
      and analyzed using thematic analysis; closed questions were analyzed using
      descriptive analysis. Results Participants felt that RT was enjoyable (90%) and
      beneficial for their affected arm (100%). From the open question data, it was
      found that the intervention was effective for the impaired arm especially in the
      sub-acute stage. Main reported concerns were that tDCS caused painful, itching
      and burning sensations and RT was sometimes tiring and difficult. Participants
      recommended that future research should focus on designing a more comfortable
      method of tDCS and develop a robot that promotes hand movements. Conclusions This
      study provides new knowledge about the benefits and barriers associated with
      these technologies which are crucial to the future effective implementation of
      these tools in practice.

PMID- 30236034
TI  - The TEAM model for mental health promotion among school-going adolescents.
AB  - OBJECTIVE: This paper reports on the process followed in developing the "TEAM"
      (an acronym for the proposed intervention) model for the promotion of mental
      health among school-going adolescents. METHODS: A sequential explanatory mixed
      method combining both quantitative and qualitative approaches was used to gain in
      depth understanding of the experiences of adolescents, school health nurses and
      teachers in dealing with emotional and social problems in high schools. Data
      collection was conducted in 4 phases from 2012 to 2015 and included a desk review
      of literature, qualitative interviews with 12 school teachers; qualitative
      interviews with 10 school health nurses and quantitative interviews with 347
      adolescents. The quantitative tool that was used for the study was based on the
      Social and Emotional Learning Model. RESULTS: Key findings from the study
      revealed inappropriate handling of emotions by adolescents, leading them to form
      destructive groups (gangs); involvement in alcohol and substance abuse;
      disrespect; and adolescent pregnancy. CONCLUSION: A universal team-oriented
      collaborative model that will assist adolescents to shift negative energy and
      attitudes to positive and productive lifestyles is required. The TEAM model
      centres all the activities of a collaborative and focused team on the
      facilitation of a sense of belonging, ownership and complete engagement of pupils
      in schools that will contribute positively to social and emotional well-being.

PMID- 30236035
TI  - Psychological effects of multimedia-induced sexualisation of girls in middle
      childhood: a systematic literature review.
AB  - OBJECTIVE: The aim of this study was to systematically review available
      literature pertaining to the psychological effects of multimedia-induced
      sexualisation of girls in middle childhood (between the ages of 6 and 12 years
      old). METHOD: A systematic review was conducted through a comprehensive
      electronic search. Nineteen studies were included in the review and the data was
      analysed by means of qualitative content analysis. RESULTS: Two themes were
      identified, namely: 1) detrimental psychological effects of sexualisation; and 2)
      beneficial psychological effects of sexualisation. Findings appeared to indicate
      that the psychological effects on girls in middle childhood resulting from
      sexualisation, such as internalisation, mental health problems, objectification
      and gender stereotyping, were more likely to be detrimental than beneficial to
      their well-being. The review also found a paucity of research on the topic within
      developing countries. Consequently, the authors recommended a precautionary
      approach pertaining to sexualisation of girls in middle childhood. CONCLUSION: A
      thorough understanding of the topic is valuable as it can inform a preventative
      and proactive management approach. It can especially assist in informing policy
      as well as therapists by informing their developmental conceptualisation and
      treatment of girls in middle childhood.

PMID- 30236036
TI  - Contrasting mental health correlates of physical and sexual abuse-related shame.
AB  - OBJECTIVE: This study represents an initial attempt to contrast behavioural and
      mental health correlates of shame as a result of physical abuse (PA) and sexual
      abuse (SA). Because they are distinctive forms of injury, it is possible that
      corollary shame from these injuries follows unique trajectories and ultimately
      results in different health challenges. METHOD: Self-report data from a survey on
      the health of youth receiving protective services for reasons of PA and SA was
      used. It included standardised measures, such as the Childhood Trauma
      Questionnaire, Trauma Symptoms Checklist for Children, the Brief Symptoms
      Inventory, the Rutgers Alcohol Problem Index, and the South Oaks Gambling Screen.
      New measures of abuse-related shame, maltreatment, and substance use were also
      employed. Linear regression analyses were performed to determine whether level of
      shame was linked to mental health and behaviour issues, after controlling for
      level of abuse. RESULTS: Results were similar for shame as a result of PA and SA
      victimisation. After accounting for shared variance with abuse severity, both
      measures were linked to a full spectrum of mental health issues, such as
      depression (SA r2 = 0.30, PA r2 = 0.28), anxiety (SA r2 = 0.27, PA r2 = 0.20),
      post-traumatic stress (SA r2 = 0.26, PA r2 = 0.19), interpersonal sensitivity (SA
      r2 = 0.17, PA r2 = 0.22), and psychoticism (SA r2 = 0.19, PA r2 = 0.20), but not
      to gambling or substance use problems. PA-related shame was associated with
      suicidality (r2 = 0.05). CONCLUSIONS: Keeping in mind that this was largely a
      cross-sectional study and that causality cannot be inferred, the results seem to
      indicate that youth suffering from abuse-related shame are particularly
      vulnerable to mental health problems, but not to efforts to numb their
      problematic thoughts and feelings through gambling and substance use. Shame could
      serve as an early indicator of which child protection recipients are most in need
      of preventive efforts.

PMID- 30236037
TI  - A case study of two adolescent-parent pairs describing the association between
      vagal tone and social-emotional adjustment during a Positive Cognitive Behaviour
      Therapy Programme.
AB  - OBJECTIVE: A case study describing the association between vagal tone and social
      emotional adaptation in two distressed adolescent-parent (A-P) pairs during a
      Positive Cognitive Behaviour Therapy Programme (P-CBTP). METHODS: Two A-P pairs
      completed a P-CBTP with pre- and post-intervention biosocial-emotional
      assessments; weekly training sessions over 7 weeks to develop individual
      strengths, new adaptive cognitions, positive discipline skills, optimism and
      knowledge on age-appropriate developmental expressions; augmented by moderate
      physical activity. Resting vagal tone and vagal reactivity were assessed by time
      domain measures of vagal activity (RMSSD). RESULTS: Social-emotional adjustment
      improved in all A-P pairs. Resting vagal tone increased over the intervention
      period, from low-to-low-normal towards average-for-normal in three subjects. The
      fourth individual had excessive pre-intervention resting vagal tone that declined
      in the direction of normal over the intervention period. Vagal reactivity in
      response to orthostatic stress remained the same pre- to post-intervention.
      CONCLUSIONS: Changes in resting vagal tone demonstrated improvements in
      psychological functioning in all four subjects over the period of intervention.
      Results supported the view of the association between vagal tone and mental
      health not being an absolute positive relationship, but that low, as well as
      excessive, vagal tone may be maladaptive. Indications are that the same may apply
      to vagal reactivity to psychological stress. More studies need to examine the
      association between resting vagal tone and emotion regulation in A-P
      relationships during P-CBTP, keeping in mind that a linear relationship cannot
      summarily be expected in population studies.

PMID- 30236038
TI  - The development of anxiety symptomatology among juvenile offenders: the roles of
      maternal substance abuse and unemployment.
AB  - This research examined the development of anxiety across adolescence and early
      adulthood among a sample of juvenile offenders comprising males and females. In
      addition, despite the understanding of maternal substance abuse and maternal
      unemployment as risk factors predicting development of anxiety, this research
      examined the interaction between these two characteristics for doing so. Analyses
      used group-based trajectory modelling to provide descriptive representation of
      general developmental patterns of anxiety. Next, a series of multinomial logistic
      regression models were estimated to examine the effects of baseline covariates on
      the relative risk of assignment to the elucidated trajectory groups. A three
      group model best fit the data, comprising low, moderate, and high anxiety
      trajectory groups. Results from the regression models indicate that the
      interaction between maternal unemployment and maternal substance abuse history
      significantly increased the risk of assignment to the high anxiety group.

PMID- 30236039
TI  - Pathology and Case Definition of Severe Perkinsea Infection of Frogs.
AB  - Severe Perkinsea infection (SPI) is an emerging disease of frogs responsible for
      mass mortalities of tadpoles across the United States. It is caused by protozoa
      belonging to the phylum Perkinsozoa that form a distinct group referred to as the
      Pathogenic Perkinsea Clade of frogs. In this work, we provide detailed
      description of gross and histologic lesions from 178 naturally infected tadpoles,
      including 10 species from 22 mortality events and 6 amphibian health monitoring
      studies from diverse geographic areas. On external examination, we observed
      abdominal distension (10, 5.6%), cutaneous erythema and petechia (3, 1.7%),
      subcutaneous edema (3, 1.7%), and areas of white skin discoloration (3, 1.7%). On
      macroscopic examination of internal organs, we found hepatomegaly (68, 38.2%),
      splenomegaly (51, 28.7%), nephromegaly (47, 26.4%), ascites (15, 8.4%), segmental
      irregular thickening and white discoloration of the intestine (8, 4.5%),
      pancreatomegaly (4, 2.2%), and pancreatic petechia (1, 0.6%). Histologically,
      over 60% of the liver (148/165, 89.7%), kidney (113/147, 76.9%), spleen (96/97,
      99%), and pancreas (46/68, 67.6%) were invaded by myriad intracellular and
      extracellular Perkinsea hypnospore-like and trophozoite-like organisms. Numerous
      other tissues were affected to a lesser extent. Mild histiocytic inflammation
      with fewer lymphocytes or eosinophils was commonly observed in areas of infection
      that were not obscured by lympho-granulocytic hematopoietic tissue. In light of
      these observations, we suggest a logical pathogenesis sequence. Finally, we
      propose a "case definition" for SPI to promote standardized communication of
      results and prevent misdiagnosis with epidemiological and pathologically
      overlapping diseases such as ranavirosis.

PMID- 30236041
TI  - Correlates of HIV prevalence among female sex workers in four north and east
      Indian states: findings of a national bio-behavioural survey.
AB  - The socio-demographic, sex work characteristics and the factors affecting HIV
      prevalence among female sex workers (FSWs) are not well known in low prevalence
      states showing rising trends within the HIV epidemic. This paper studies these
      attributes among FSWs in three north (Punjab, Rajasthan and Uttar Pradesh) and
      one east Indian states (Jharkhand). Integrated Biological and Behavioural
      Surveillance (IBBS) data, collected from 4491 FSWs in the study states, were
      analysed, with HIV status as the dependent variable and several socio
      demographic, sex work, knowledge and agency characteristics as independent
      variables. Multivariate analysis found a number of factors such as age above 25
      years (adjusted odds ratio [AOR] 5.0, 95% confidence interval [CI] 1.4-18.1),
      client solicitation in rented rooms (AOR 2.8, 95% CI 1.2-6.4) and the use of
      mobile phones for client solicitation (AOR 5.1, 95% CI 1.6-16.0) to be
      significantly associated with HIV risk. The study found low levels of HIV
      programme services uptake and HIV/AIDS knowledge among FSWs in the study states.
      There is an urgent need to focus on these risk factors for improving the
      effectiveness of the ongoing HIV prevention efforts and attaining the
      'Sustainable Development Goals' goal of 'Ending the AIDS epidemic' by 2030.

PMID- 30236040
TI  - Characterization of Cell Membrane Permeability In Vitro Part I: Transport
      Behavior Induced by Single-Pulse Electric Fields.
AB  - Most experimental studies of electroporation focus on permeabilization of the
      outer cell membrane. Some experiments address delivery of ions and molecules into
      cells that should survive; others focus on efficient killing of the cells with
      minimal temperature rise. A basic method for quantifying electroporation
      effectiveness is measuring the membrane's diffusive permeability. More
      specifically, comparisons of membrane permeability between electroporation
      protocols often rely on relative fluorescence measurements, which are not able to
      be directly connected to theoretical calculations and complicate comparisons
      between studies. Here we present part I of a 2-part study: a research method for
      quantitatively determining the membrane diffusive permeability for individual
      cells using fluorescence microscopy. We determine diffusive permeabilities of
      cell membranes to propidium for electric field pulses with durations of 1 to 1000
      MUs and strengths of 170 to 400 kV/m and show that diffusive permeabilities can
      reach 1.3+/-0.4*10-8 m/s. This leads to a correlation between increased membrane
      permeability and eventual propidium uptake. We also identify a subpopulation of
      cells that exhibit a delayed and significant propidium uptake for relatively
      small single pulses. Our results provide evidence that cells, especially those
      that uptake propidium more slowly, can achieve large permeabilities with a single
      electrical pulse that may be quantitatively measured using standard fluorescence
      microscopy equipment and techniques.

PMID- 30236042
TI  - Efficacy of sinecatechins 10% as proactive sequential therapy of external genital
      warts after laser CO2 ablative therapy: The PACT study (post-ablation
      immunomodulator treatment of condylomata with sinecatechins): a randomized,
      masked outcome assessment, multicenter trial.
AB  - External genital warts (EGW) are the most common viral sexually transmitted
      infection. Ablative treatments like cryotherapy, curettage, and CO2 laser
      therapies offer rapid onset of effect, fast clearance, and reduction of virus
      load. However, these procedures are associated with high recurrence rates (RRs)
      ranging from 20% to 77% in the short and medium terms and do not provide
      sustained clearance. After laser therapy removal of EGW, an RR up to 77% has been
      reported. Topical sinecatechins (TS) 10% is a patient-applied regimen for the
      treatment of EGW with a low RR (<6.5%) at three months after completion of the
      therapy in the pivotal trials conducted so far. Sinecatechins can be considered a
      suitable proactive sequential therapy (PST) after ablative strategies to obtain a
      low RR. So far, no prospective data are available regarding the efficacy of
      sinecatechins 10% as PST. We evaluated the efficacy and tolerability of TS 10%
      ointment applied twice daily in subjects with "difficult to treat" EGW after CO2
      laser ablative treatment in a prospective controlled trial. A total of 87
      subjects (76 men and 11 women; mean age 42 years) were enrolled in this three
      month masked outcome assessment parallel group trial with imbalanced
      randomization allocation (2:1). One week after a successful CO2 laser treatment,
      60 subjects were randomized to TS 10% treatment and 27 subjects to no treatment
      (control group: ConTRol (CTR); no sequential therapy). All patients had a history
      of an average of 4.5 previous ablative treatments in the last 12 months due to
      recurrent EGW. Mean (standard deviation) baseline number of treated lesions was
      6.5 (2.7). One subject in the TS arm dropped out due to burning sensation after
      the application of the product. Therefore, 86 subjects completed the study. After
      three months, in the TS group, three subjects presented new EGW lesions (RR: 5%)
      on treated sites. In the CTR group, eight subjects presented new EGW lesions (RR:
      29%) on treated sites (p = 0.0024; odds ratio: 0.16; 95% confidence interval:
      0.04-0.68). In the TS group, 34 subjects (56%) reported mild to moderate erythema
      or burning sensation at the application site. In this prospective multicenter
      trial, the use of TS 10% as PST after ablative treatment with CO2 laser was
      associated with a lower recurrence rate of new EGW lesions in the short term in
      comparison with the control group. Comparative larger trials are warranted to
      evaluate the role of this approach as PST (Trial Registration Number:
      ISRCTN44037479).

PMID- 30236043
TI  - Lung ultrasound in the management of pneumocystis pneumonia: A case series.
AB  - Despite the decline in HIV mortality and morbidity, Pneumocystis jirovecii
      pneumonia (PJP) is still frequently seen, particularly in patients with a low
      CD4+ cell count. We present a case series where we analyzed the possible role of
      lung ultrasound (LUS) in the management of PJP in a real-life clinical setting.
      We describe the ultrasound findings from a consecutive series of six HIV patients
      hospitalized for PJP, all with a favorable outcome, and evaluated with LUS at
      admission in our ward and then repeated this once during the hospitalization.
      Multiple B lines indicating interstitial syndrome were detected at admission in
      all cases, with a bilateral asymmetric pattern mostly localized in middle and
      upper lobes. In the follow-up LUS, we noted a substantially improved pattern in
      all patients, observing a reduction of B lines which correlated with clinical
      amelioration. One patient at admission and three patients during the follow-up
      showed lung consolidations with hyperechoic spots inside, that might be typical
      of the disease. In conclusion, LUS could be a practical and noninvasive imaging
      tool for supporting diagnosis and treatment response of PJP.

PMID- 30236044
TI  - Small Airway Obstruction, Dynamic Hyperinflation and Gas Trapping despite Normal
      Airway Sensitivity to Methacholine in Adults with Chronic Cough.
AB  - RATIONALE: The clinical relevance of cough during methacholine challenge in
      individuals with normal airway sensitivity is unknown. OBJECTIVES: To compare the
      mechanical responses of individuals with chronic cough who cough during high-dose
      methacholine bronchoprovocation and have normal versus increased airway
      sensitivity to healthy controls. METHODS: Fifteen healthy participants (CONTROL)
      aged 26+/-7 yrs (Mean +/- SD), and thirty-two participants aged 42+/-14 years
      with chronic cough and suspected asthma completed high-dose methacholine
      challenge testing. Spirometry and lung volumes were compared at the maximum
      response (MAX) amongst: i) ASTHMA (n=15, provocative concentration of
      methacholine causing a 20% fall in FEV1 from baseline [PC20] 4.71+/-1.37 mg/mL);
      ii) methacholine-induced cough with normal airway sensitivity (COUGH, n=14, PC20
      41.2+/-18.7 mg/mL for 3 participants with a measureable PC20); and iii) CONTROL
      (n=15; PC20 93.4+/-95.4 mg/mL for 4 participants with a measurable PC20).
      Esophageal-pressure derived pulmonary mechanics were compared at MAX for the
      ASTHMA and COUGH groups. MEASUREMENTS AND MAIN RESULTS: From baseline to MAX,
      FEV1 and FEF25-75% decreased more in ASTHMA (-36.2+/-3.8 %pr; -47.1+/-6.9 %pr,
      respectively) than COUGH (-12.2+/-3.0 %pr (P<0.001); -24.7+/-6.5 %pr (P<0.001),
      respectively) and CONTROL (-13.7+/-7.4 %pr (P<0.001); -32.8+/-21.0 %pr (P<0.017),
      respectively). In both ASTHMA and COUGH, IC decreased by 500-800 mL, and FRC and
      RV increased by approximately 800 mL. CONCLUSIONS: Individuals with COUGH develop
      dynamic hyperinflation and gas trapping comparable to individuals with ASTHMA
      despite less bronchoconstriction and smaller reductions in mid-to-late expiratory
      flows, which leads us to believe that COUGH is a distinct phenotype on the airway
      disease continuum.

PMID- 30236045
TI  - Diaphragm muscle function following mid-cervical contusion injury in rats.
AB  - Mid-cervical spinal cord contusion injury results in tissue damage, disruption of
      spinal pathways, and motor neuron loss. Unilateral C4 contusion results in loss
      of 40-50% of phrenic motor neurons ipsilateral to the injury (~25% of the total
      phrenic motor neuron pool). Over time after unilateral C4 contusion injury,
      diaphragm muscle (DIAm) electromyogram (EMG) activity increases both
      contralateral and ipsilateral to the side of injury in rats, suggesting
      compensation due to increased activation of the surviving motor neurons. However,
      the impact of contusion injury on DIAm force generation is less clear.
      Transdiaphragmatic pressure (Pdi) was measured across motor behaviors over time
      after unilateral C4 contusion injury in adult male Sprague-Dawley rats. Maximum
      Pdi (Pdimax) was elicited by bilateral phrenic nerve stimulation at 7 days post
      injury. We hypothesized that Pdimax is reduced following unilateral C4 contusion
      injury, while ventilatory behaviors of the DIAm are unimpaired. In support of our
      hypothesis, Pdimax was reduced by ~25% after unilateral C4 contusion, consistent
      with the extent of phrenic motor neuron loss following contusion injury. One day
      post-contusion injury, the Pdi amplitude during airway occlusion was reduced from
      ~30 to ~20 cm H2O, but this reduction was completely reversed by 7 days post
      injury. Ventilatory behaviors (~10 cm H2O), DIAm specific force, and muscle fiber
      cross-sectional area did not differ between the laminectomy and contusion groups.
      These results indicate that the large reserve capacity for DIAm force generation
      allows for higher-force motor behaviors to be accomplished despite motor neuron
      loss, likely reflecting changes in motor unit recruitment.

PMID- 30236046
TI  - Chronic intermittent nicotine delivery via lung alveolar region-targeted aerosol
      technology produces circadian pharmacokinetics in rats resembling human smokers.
AB  - Cigarette smoke is an aerosol containing microparticles that carry nicotine into
      the lung alveolar region where nicotine is rapidly absorbed into circulation.
      Nicotine exposure in smokers is a chronic intermittent process, with episodic
      intake during wakefulness and abstinence during sleep resulting in circadian
      fluctuation of blood nicotine levels. We developed an integrated platform where
      freely moving rodents can be exposed to episodic nicotine aerosol on an
      investigator-designed schedule. Plasma nicotine and its metabolite cotinine
      levels were determined with a LC-MS/MS method. We characterized the aerosol in
      the breathing zone of the rodent exposure chamber. The droplet size distribution
      was within the respirable diameter range. The system can generate a wide range of
      nicotine concentrations in air that meet a variety of experimental needs. Rats
      were exposed to nicotine aerosol once every half hour in the dark phase of 12/12
      hour dark/light cycles for 10 days. We optimized the parameters of aerosol
      generation and exposure: plasma nicotine and cotinine concentrations reached 30
      35 ng/ml and 190-240 ng/ml, respectively. The nicotine levels and circadian
      patterns resembled the pharmacokinetic pattern of human smokers. In summary, we
      developed an aerosol system that can produce clinically relevant chronic
      intermittent nicotine exposure in unanesthetized, unrestrained rodents with route
      of administration and circadian blood pharmacokinetics resembling human smokers.
      This methodology is a novel tool for understanding the health effects of chronic
      intermittent nicotine exposure such as with tobacco cigarettes and E-cigarettes
      for studies of behavior, pharmacology and toxicology, nicotine addiction, tobacco
      related diseases, teratogenicity, and for the discovery of therapeutics.

PMID- 30236047
TI  - Computational Model-Based Assessment of Baroreflex Function from Response to
      Valsalva Maneuver.
AB  - Functional metrics of autonomic control of heart rate, including baroreflex
      sensitivity, have been shown to be strongly associated with cardiovascular risk.
      A decrease in baroreflex sensitivity with aging is hypothesized to represent a
      contributing causal factor in the etiology of primary hypertension. To assess
      baroreflex function in human subjects, two complimentary methods to simulate the
      response in heart rate elicited by the Valsalva maneuver were developed and
      applied to data obtained from a cohort of healthy normal volunteers. The first
      method is based on representing the baroreflex arc as a simple linear filter,
      transforming changes in arterial pressure to changes in R-R interval. The second
      method invokes a physiologically based model for arterial mechanics, afferent
      baroreceptor strain-dependent firing, and control of heart rate via central
      autonomic response to changes in afferent inputs from aortic and carotid sensors.
      Analysis based on the linear filter model reveals that the effective response
      time of the baroreflex arc tends to increase with age in healthy subjects and
      that the response time/response rate is a predictor of resting systolic pressure.
      Similar trends were obtained based on the physiologically based model. Analysis
      of the Valsalva response using the physiologically based model further reveals
      that different afferent inputs from the carotid sinus and the aortic arch
      baroreceptors govern different parts of the heart rate response. The observed
      relationship between baroreflex sensitivity and systolic pressure is surprising
      because hypertensive subjects were excluded from the study, and there was no
      observed relationship between arterial pressure and age.

PMID- 30236048
TI  - Attenuation of human hypoxic pulmonary vasoconstriction by acetazolamide and
      methazolamide.
AB  - RATIONALE: Acetazolamide, a carbonic anhydrase inhibitor used for preventing
      altitude illness attenuates hypoxic pulmonary vasoconstriction (HPV) while
      improving oxygenation. Methazolamide, an analog of acetazolamide, is more
      lipophilic, has a longer half-life, and activates a major antioxidant
      transcription factor. However, its influence on the hypoxic pulmonary response in
      humans is unknown. OBJECTIVE: To determine if a clinically relevant dosing of
      methazolamide improves oxygenation, attenuates HPV and augments plasma
      antioxidant capacity in men exposed to hypoxia when compared to an established
      dosing of acetazolamide known to suppress HPV. METHODS: In this double-blind,
      placebo-controlled, cross-over trial, eleven participants were randomized to
      treatments with methazolamide (100mg b.i.d.) and acetazolamide (250mg t.i.d.) for
      two days prior to 60 minutes of hypoxia (FIO2~0.12). MEASUREMENTS: Pulmonary
      artery systolic pressure (PASP), alveolar ventilation (VA), blood gases and
      markers of redox status were measured. Pulmonary vascular sensitivity to hypoxia
      was determined by indexing PASP to alveolar PO2. RESULTS: Acetazolamide caused
      greater metabolic acidosis compared with methazolamide, but the augmented VA and
      improved oxygenation with hypoxia were similar. The rise in PASP with hypoxia was
      lower with methazolamide (9.0 +/- 0.9 mmHg) and acetazolamide (8.0 +/- 0.7 mmHg)
      compared with placebo (14.1 +/- 1.3 mmHg; P < 0.05). The pulmonary vascular
      sensitivity to hypoxia (DeltaPASP/DeltaPAO2) was reduced equally by both drugs.
      Only acetazolamide improved the non-enzymatic plasma antioxidant capacity.
      CONCLUSIONS: Although acetazolamide only had plasma antioxidant properties,
      methazolamide led to similar improvements in oxygenation and reduction in HPV at
      a dose causing less metabolic acidosis than acetazolamide in humans.

PMID- 30236049
TI  - Habitual Aerobic Exercise and Circulating Proteomic Patterns in Healthy Adults:
      Relation to Indicators of Healthspan.
AB  - Habitual aerobic exercise enhances physiological function and reduces risk of
      morbidity and mortality throughout life, but the underlying molecular mechanisms
      are largely unknown. The circulating proteome reflects the intricate network of
      physiological processes maintaining homeostasis, and may provide insight into the
      molecular transducers of the health benefits of physical activity. In this
      exploratory study, we assessed the plasma proteome (SOMAscan proteomic assay;
      1129 proteins) of healthy sedentary or aerobic exercise-trained young women and
      young and older men (n= 47). Using weighted correlation network analysis to
      identify clusters of highly co-expressed proteins, we characterized 10 distinct
      plasma proteomic modules (patterns). In healthy young (24+/-1 years) men and
      women, 4 modules were associated with aerobic exercise status, and 1 with
      participant sex. In healthy young and older (64+/-2 years) men, 5 modules
      differed with age, but 2 of these were partially preserved at young adult levels
      in older men who exercised; among all men, 4 modules were associated with
      exercise status, including 3 of the 4 identified in young adults. Exercise-linked
      proteomic patterns were related to pathways involved in wound healing, regulation
      of apoptosis, glucose-insulin and cellular stress signaling, and
      inflammation/immune responses. Importantly, several of the exercise-related
      modules were associated with physiological and clinical indicators of healthspan,
      including diastolic blood pressure, insulin resistance, maximal aerobic capacity,
      and vascular endothelial function. Overall, these findings provide initial
      insight into circulating proteomic patterns modulated by habitual aerobic
      exercise in healthy young and older adults, the biological processes involved,
      and their relation to indicators of healthspan.

PMID- 30236050
TI  - Effects of stroke injury on the shear modulus of the lower leg muscle during
      passive dorsiflexion.
AB  - Contractures are common complications of a stroke. The spatial location of the
      increased stiffness among plantar flexors and its variability among survivors
      remain unknown. This study assessed the mechanical properties of the lower leg
      muscles in stroke survivors during passive dorsiflexions. Stiffness was estimated
      through the measurement of the shear modulus. Two experiments were independently
      conducted where participants laid supine: with the knee extended (experiment 1,
      n=13 stroke survivors and n=13 controls), or with the knee flexed at 90 degrees 
      (experiment 2, n=14 stroke survivors and n=14 controls). The shear modulus of
      plantar flexors (gastrocnemius medialis [3 locations], gastrocnemius lateralis
      [3], soleus [2], flexor digitorum longus, flexor hallucis longus), peroneus
      longus) and dorsi flexors (tibialis anterior, and extensor digitorum longus) was
      measured using ultrasound shear wave elastography during passive dorsiflexions (2
      degrees /sec). At the same ankle angle, stroke survivors displayed higher shear
      modulus than controls for gastrocnemius medialis and gastrocnemius lateralis
      (knee extended); and soleus (knee flexed). Very low shear modulus were found for
      the other muscles. The adjustment for muscle slack angle suggested that the
      increased shear modulus was arising from consequences of contractures. The
      stiffness distribution between muscles was consistent across participants with
      the highest shear modulus reported for the most distal regions of gastrocnemius
      medialis (knee extended) and soleus (knee flexed). These results provide a better
      appreciation of stiffness locations among plantar flexors of stroke survivors,
      and can provide evidence for the implementation of clinical trials to evaluate
      targeted interventions applied on these specific muscle regions.

PMID- 30236051
TI  - Moderate Intensity Exercise Reduces Activated and Apoptotic Endothelial
      Microparticles in Healthy Midlife Women.
AB  - : Endothelial microparticles (EMPs) are related to cardiovascular disease (CVD)
      risk. Risk factors for CVD increase with menopause, while greater
      cardiorespiratory fitness is generally expected to reduce CVD risk. The effects
      of habitual physical activity on endothelial health may be due in part to the
      effect of acute exercise on circulating EMPs. PURPOSE: To evaluate the effect of
      an acute bout of exercise on CD62E+ and CD31+/42b- EMPs in healthy fit midlife
      women at different menopausal stages. METHODS: Healthy, active premenopausal
      (PRE), perimenopausal (PERI) and postmenopausal (POST) women completed a single
      bout of moderate intensity treadmill exercise. Activated (CD62E+) and apoptotic
      (CD31+/42b-) EMPs were evaluated before and 30 minutes after exercise using
      fluorescent activated cell sorting. In an exploratory analysis, these results
      were compared to data from low-fit peri- and postmenopausal women. Differences by
      group and time point were evaluated with repeated-measure ANOVAs. RESULTS: There
      was a reduction in the number of total microparticles (p<0.001), CD62E+ (p=0.003)
      and CD31+/42b- (p<0.001) EMPs/MUl plasma following acute exercise. The percentage
      of CD62E+ EMPs increased with acute exercise (p<0.001), while the percentage of
      CD31+/42b-EMPs did not change (p=0.40). There was no effect of menopausal status
      on CD62E+or CD31+/42b- EMPs, or on total microparticles (all p>0.05). The
      exploratory analysis revealed that low-fit women had similar changes in EMPs with
      acute exercise. CONCLUSIONS: Acute moderate intensity exercise reduces CD62E+and
      CD31+/42b- EMPs, as well as total microparticles, in healthy midlife women. These
      effects occurred despite differences in menopausal status and fitness.

PMID- 30236052
TI  - Passive stretch regulates skeletal muscle glucose uptake independent of nitric
      oxide synthase.
AB  - Skeletal muscle contraction increases glucose uptake via an insulin-independent
      mechanism. Signaling pathways arising from mechanical strain are activated during
      muscle contractions, and mechanical strain in the form of passive stretching
      stimulates glucose uptake. However, the exact mechanisms regulating stretch
      stimulated glucose uptake are not known. Since nitric oxide synthase (NOS) has
      been implicated in the regulation of glucose uptake during ex vivo and in situ
      muscle contractions and during exercise, and NO is increased with stretch, we
      examined whether the increase in muscle glucose uptake during stretching involves
      NOS. We passively stretched isolated EDL muscles (15 min at ~100-130 mN) from
      control mice and mice lacking either neuronal NOSu (nNOSu) or endothelial NOS
      (eNOS) isoforms, as well as used pharmacological inhibitors of NOS. Stretch
      significantly increased muscle glucose uptake approximately 2-fold (P < 0.05),
      and this was unaffected by the presence of the NOS inhibitors NG-monomethyl-L
      arginine (L-NMMA; 100 uM) or NG-nitro-L-arginine methyl ester (L-NAME; 100 uM).
      Similarly, stretch-stimulated glucose uptake was not attenuated by deletion of
      either eNOS or nNOSu isoforms. Furthermore, stretching failed to increase
      skeletal muscle NOS enzymatic activity above resting levels. These data clearly
      demonstrate that stretch-stimulated skeletal muscle glucose uptake is not
      dependent on NOS.

PMID- 30236053
TI  - Contemporary image-based methods for measuring passive mechanical properties of
      skeletal muscles in vivo.
AB  - Skeletal muscles' primary function in the body is mechanical - to move and
      stabilize the skeleton. As such, their mechanical behavior is a key aspect of
      their physiology. Recent developments in medical imaging technology have enabled
      quantitative studies of passive muscle mechanics, ranging from measurements of
      intrinsic muscle mechanical properties, such as elasticity and viscosity, to 3D
      muscle architecture and dynamic muscle deformation and kinematics. In this review
      we summarize the principles and applications of contemporary imaging methods that
      have been used to study the passive mechanical behaviour of skeletal muscles.
      Elastography measurements can provide in vivo maps of passive muscle mechanical
      parameters, and both MRI and ultrasound methods are available (magnetic resonance
      elastography and ultrasound shear wave elastography, respectively). Both have
      been shown to differentiate between healthy muscle and muscles affected by a
      broad range of clinical conditions. Detailed muscle architecture can now be
      depicted using diffusion tensor imaging, which is particularly useful for
      computational modeling of muscle, but also has potential in assessing
      architectural changes in muscle disorders. More dynamic information about muscle
      mechanics can be obtained using a range of dynamic magnetic resonance imaging
      methods, which characterize the detailed internal muscle deformations during
      motion. There are several MRI techniques available (e.g. Phase-contrast MRI,
      Displacement encoded MRI, and 'tagged' MRI), each of which can be collected in
      synchrony with muscle motion, and post-processed to quantify muscle deformation.
      Together, these modern imaging techniques can characterize muscle motion,
      deformation, mechanical properties and architecture, providing complementary
      insights into skeletal muscle function.

PMID- 30236054
TI  - The sucrose non-fermenting-1-related protein kinases SAPK1 and SAPK2 function
      collaboratively as positive regulators of salt stress tolerance in rice.
AB  - BACKGROUND: The sucrose non-fermenting-1-related protein kinase 2 family (SnRK2s)
      unifies different abiotic stress signals in plants. To date, the functions of two
      rice SnRK2s, osmotic stress/ABA-activated protein kinase 1 (SAPK1) and SAPK2,
      have been unknown. We investigated their roles in response to salt stress by
      generating loss-of-function lines using the CRISPR/Cas9 system and by
      overexpressing these proteins in transgenic rice plants. RESULTS: Expression
      profiling revealed that SAPK1 and SAPK2 expression were strongly induced by
      drought, NaCl, and PEG treatment, but not by ABA. SAPK2 expression was highest in
      the leaves, followed by the roots, whereas SAPK1 was highest expressed in roots
      followed by leaves. Both proteins were localized to the nucleus and the
      cytoplasm. Under salt stress, sapk1, sapk2 and, in particular, sapk1/2 mutants,
      exhibited reduced germination rates, more severe growth inhibition, more distinct
      chlorosis, reduced chlorophyll contents, and reduced survival rates in comparison
      with the wild-type plants. In contrast, SAPK1- and SAPK2-overexpression lines had
      increased germination rates and reduced sensitivities to salt; including mild
      reductions in growth inhibition, reduced chlorosis, increased chlorophyll
      contents and improved survival rates in comparison with the wild-type plants.
      These results suggest that SAPK1 and SAPK2 may function collaboratively as
      positive regulators of salt stress tolerance at the germination and seedling
      stages. We also found that SAPK1 and SAPK2 affected the osmotic potential
      following salt stress by promoting the generation of osmotically active
      metabolites such as proline. SAPK1 and SAPK2 also improved reactive oxygen
      species (ROS) detoxification following salt stress by promoting the generation of
      ROS scavengers such as ascorbic acid, and by increasing the expression levels of
      proteins such as superoxide dismutase (SOD) and catalase (CAT). SAPK1 and SAPK2
      may function collaboratively in reducing Na+ toxicity by affecting the Na+
      distribution between roots and shoots, Na+ exclusion from the cytoplasm, and Na+
      sequestration into the vacuoles. These effects may be facilitated through the
      expression of Na+-and K+-homeostasis-related genes. CONCLUSION: SAPK1 and SAPK2
      may function collaboratively as positive regulators of salt stress tolerance at
      the germination and seedling stages in rice. SAPK1 and SAPK2 may be useful to
      improve salt tolerance in crop plants.

PMID- 30236056
TI  - Detecting differentially expressed genes for syndromes by considering change in
      mean and dispersion simultaneously.
AB  - BACKGROUND: Using next-generation sequencing technology to measure gene
      expression, an empirically intriguing question concerns the identification of
      differentially expressed genes across treatment groups. Existing methods aim to
      identify genes whose mean expressions differ among treatment groups by assuming
      equal dispersion across all groups. For syndromes, however, various combinations
      of gene expression alterations can result in the same disease, leading to greater
      heteroscedasticity in the biological replicates in the disease group compared to
      the normal group. Traditional methods that only consider changes in the mean will
      fail to fully analyze gene expression in such a scenario. In addition, sequencing
      technology is relatively expensive; most labs can only afford a few replicates
      per treatment group, which poses further challenges to reliably estimating the
      mean and dispersion under each treatment condition. RESULTS: We designed an
      empirical Bayes method and a pooled permutation test to simultaneously consider
      the change in mean and dispersion across treatment groups. We further computed
      confidence intervals based on Bayes estimates to identify differentially
      expressed genes that are unique to each disease sample as well as those that are
      common across all disease samples. We illustrated our method by applying it to
      gene expression data from a large offspring syndrome experiment, which motivated
      this study. We compared our method to competing approaches through simulation
      studies that mimicked the real datasets to demonstrate the effectiveness of our
      proposed method. CONCLUSIONS: We will show that, compared to popular methods that
      only aim to find the difference in the mean, our method can capture greater
      variation in the disease group to effectively identify differentially expressed
      genes for syndromes.

PMID- 30236055
TI  - Positive selection at sites of chemosensory genes is associated with the recent
      divergence and local ecological adaptation in cactophilic Drosophila.
AB  - BACKGROUND: Adaptation to new hosts in phytophagous insects often involves
      mechanisms of host recognition by genes of sensory pathways. Most often the
      molecular evolution of sensory genes has been explained in the context of the
      birth-and-death model. The role of positive selection is less understood,
      especially associated with host adaptation and specialization. Here we aim to
      contribute evidence for this latter hypothesis by considering the case of
      Drosophila mojavensis, a species with an evolutionary history shaped by multiple
      host shifts in a relatively short time scale, and its generalist sister species,
      D. arizonae. RESULTS: We used a phylogenetic and population genetic analysis
      framework to test for positive selection in a subset of four chemoreceptor genes,
      one gustatory receptor (Gr) and three odorant receptors (Or), for which their
      expression has been previously associated with host shifts. We found strong
      evidence of positive selection at several amino acid sites in all genes
      investigated, most of which exhibited changes predicted to cause functional
      effects in these transmembrane proteins. A significant portion of the sites
      identified as evolving positively were largely found in the cytoplasmic region,
      although a few were also present in the extracellular domains. CONCLUSIONS: The
      pattern of substitution observed suggests that some of these changes likely had
      an effect on signal transduction as well as odorant recognition and protein
      protein interactions. These findings support the role of positive selection in
      shaping the pattern of variation at chemosensory receptors, both during the
      specialization onto one or a few related hosts, but as well as during the
      evolution and adaptation of generalist species into utilizing several hosts.

PMID- 30236057
TI  - Isolation and characterization of native probiotics for fish farming.
AB  - BACKGROUND: Innovations in fish nutrition act as drivers for the sustainable
      development of the rapidly expanding aquaculture sector. Probiotic dietary
      supplements are able to improve health and nutrition of livestock, but respective
      bacteria have mainly been isolated from terrestrial, warm-blooded hosts, limiting
      an efficient application in fish. Native probiotics adapted to the
      gastrointestinal tract of the respective fish species will establish within the
      original host more efficiently. RESULTS: Here, 248 autochthonous isolates were
      cultured from the digestive system of three temperate flatfish species. Upon 16S
      rRNA gene sequencing of 195 isolates, 89.7% (n = 175) Gram-negatives belonging to
      the Alpha- (1.0%), Beta- (4.1%) and Gammaproteobacteria (84.6%) were identified.
      Candidate probiotics were further characterized using in vitro assays addressing
      1) inhibition of pathogens, 2) degradation of plant derived anti-nutrient
      (saponin) and 3) the content of essential fatty acids (FA) and their precursors.
      Twelve isolates revealed an inhibition towards the common fish pathogen
      Tenacibaculum maritimum, seven were able to metabolize saponin as sole carbon and
      energy source and two isolates 012 Psychrobacter sp. and 047 Paracoccus sp.
      revealed remarkably high contents of docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA). Furthermore, a rapid and cost-effective method to
      coat feed pellets revealed high viability of the supplemented probiotics over 54
      d of storage at 4 degrees C. CONCLUSIONS: Here, a strategy for the isolation and
      characterization of native probiotic candidates is presented that can easily be
      adapted to other farmed fish species. The simple coating procedure assures
      viability of probiotics and can thus be applied for the evaluation of probiotic
      candidates in the future.

PMID- 30236058
TI  - Root inoculation with Azotobacter chroococcum 76A enhances tomato plants
      adaptation to salt stress under low N conditions.
AB  - BACKGROUND: The emerging roles of rhizobacteria in improving plant nutrition and
      stress protection have great potential for sustainable use in saline soils. We
      evaluated the function of the salt-tolerant strain Azotobacter chroococcum 76A as
      stress protectant in an important horticultural crop, tomato. Specifically we
      hypothesized that treatment of tomato plants with A. chroococcum 76A could
      improve plant performance under salinity stress and sub-optimal nutrient regimen.
      RESULTS: Inoculation of Micro Tom tomato plants with A. chroococcum 76A increased
      numerous growth parameters and also conferred protective effects under both
      moderate (50 mM NaCl) and severe (100 mM NaCl) salt stresses. These benefits were
      mostly observed under reduced nutrient regimen and were less appreciable in
      optimal nitrogen conditions. Therefore, the efficiency of A. chroococcum 76A was
      found to be dependent on the nutrient status of the rhizosphere. The expression
      profiles of LEA genes indicated that A. chroococcum 76A treated plants were more
      responsive to stress stimuli when compared to untreated controls. However,
      transcript levels of key nitrogen assimilation genes revealed that the optimal
      nitrogen regimen, in combination with the strain A. chroococcum 76A, may have
      saturated plant's ability to assimilate nitrogen. CONCLUSIONS: Roots inoculation
      with A. chroococcum 76A tomato promoted tomato plant growth, stress tolerance and
      nutrient assimilation efficiency under moderate and severe salinity. Inoculation
      with beneficial bacteria such as A. chroococcum 76A may be an ideal solution for
      low-input systems, where environmental constraints and limited chemical
      fertilization may affect the potential yield.

PMID- 30236059
TI  - Transcriptomic response of female adult moths to host and non-host plants in two
      closely related species.
AB  - BACKGROUND: Divergent selection has been shown to promote speciation in many taxa
      and especially in phytophagous insects. In the Ostrinia species complex, the
      European corn borer (ECB) and adzuki bean borer (ABB) are two sibling species
      specialized to different host plants. The first is a well-known maize pest,
      whereas the second is a polyphagous species associated with various dicotyledons.
      Their specialization to host plants is driven by morphological, behavioral and
      physiological adaptations. In particular, previous studies have shown that ECB
      and ABB display marked behavior with regard to plant choice during oviposition,
      involving specific preference and avoidance mechanisms. In this study, our goal
      was to identify the mechanisms underlying this host-plant specialization in adult
      females through an analysis of their gene expression. We assembled and annotated
      a de novo reference transcriptome and measured differences in gene expression
      between ECB and ABB females, and between environments. We related differentially
      expressed genes to host preference behavior, and highlighted the functional
      categories involved. We also conducted a specific analysis of chemosensory genes,
      which are considered to be good candidates for host recognition before
      oviposition. RESULTS: We recorded more differentially expressed genes in ECB than
      in ABB samples, and noticed that the majority of genes potentially involved in
      the host preference were different between the two species. At the functional
      level, the response to plant environment in adult females involved many
      processes, including the metabolism of carbohydrates, lipids, proteins, and amino
      acids; detoxification mechanisms and immunity; and the chemosensory repertoire
      (as expected). Until now, most of the olfactory receptors described in Ostrinia
      spp. had been tested for their putative role in pheromone recognition by males.
      Here we observed that one specific olfactory receptor was clearly associated with
      ECB's discrimination between maize and mugwort conditions, highlighting a
      potential new candidate involved in plant odor discrimination in adult females.
      CONCLUSIONS: Our results are a first step toward the identification of candidate
      genes and functions involved in chemosensory processes, carbohydrate metabolism,
      and virus and retrovirus dynamics. These candidates provide new avenues for
      research into understanding the role of divergent selection between different
      environments in species diversification.

PMID- 30236060
TI  - Genome-wide analysis of long non-coding RNAs in Catalpa bungei and their
      potential function in floral transition using high-throughput sequencing.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) have crucial roles in various
      biological regulatory processes. However, the study of lncRNAs is limited in
      woody plants. Catalpa bungei is a valuable ornamental tree with a long
      cultivation history in China, and a deeper understanding of the floral transition
      mechanism in C. bungei would be interesting from both economic and scientific
      perspectives. RESULTS: In this study, we categorized C. bungei buds from early
      flowering (EF) and normal flowering (NF) varieties into three consecutive
      developmental stages. These buds were used to systematically study lncRNAs during
      floral transition using high-throughput sequencing to identify molecular
      regulatory networks. Quantitative real-time PCR was performed to study RNA
      expression changes in different stages. In total, 12,532 lncRNAs and 26,936
      messenger RNAs (mRNAs) were detected. Moreover, 680 differentially expressed
      genes and 817 differentially expressed lncRNAs were detected during the
      initiation of floral transition. The results highlight the mRNAs and lncRNAs that
      may be involved in floral transition, as well as the many lncRNAs serving as
      microRNA precursors. We predicted the functions of lncRNAs by analysing the
      relationships between lncRNAs and mRNAs. Seven lncRNA-mRNA interaction pairs may
      participate in floral transition. CONCLUSIONS: This study is the first to
      identify lncRNAs and their potential functions in floral transition, providing a
      starting point for detailed determination of the functions of lncRNAs in C.
      bungei.

PMID- 30236062
TI  - Urine cultures in a long-term care facility (LTCF): time for improvement.
AB  - BACKGROUND: Urinary tract infections (UTIs) are the most prevalent infections in
      long-term care facilities (LTCFs). Numerous studies have described the problem of
      inadequate UTI diagnosis and treatment. We assessed the role of urine cultures in
      the diagnosis and treatment of UTIs in a LTCF. METHODS: In a 370-bed non-academic
      LTCF a retrospective assessment of antibiotic (AB) prescriptions for UTIs and
      urine cultures was performed from July 2014 to January 2016. The reasons why
      physicians, including 11 nursing home physicians and 2 junior doctors, ordered
      urine cultures were recorded using questionnaires. RESULTS: During the study
      period, 378 residents were prescribed 1672 AB courses; 803 were for UTIs. One
      hundred and fifty-five urine cultures were obtained from 135 residents; 66 of
      these cultures were performed on the same day as ABs were prescribed (8% of all
      prescriptions for UTI), while 89 were not. There was a discrepancy between the
      actions that seemed logical based on the culture results and the actions that
      were actually taken in 75% of the cases. In these cases, initial AB treatment was
      not adjusted when the isolated microorganism was resistant to the AB prescribed,
      the urine culture was positive and no ABs had previously been administered, or
      ABs were prescribed and no microorganism was isolated. The most frequent reason
      for ordering a urine culture was to confirm the diagnosis of a UTI. CONCLUSION:
      In the majority of patients, AB therapy was not adjusted when the urine culture
      results suggested it may be appropriate. The physicians were erroneously
      convinced that UTIs could be diagnosed by a positive urine culture.

PMID- 30236061
TI  - Evolution of ALOG gene family suggests various roles in establishing plant
      architecture of Torenia fournieri.
AB  - BACKGROUND: ALOG (Arabidopsis LSH1 and Oryza G1) family with a conserved domain
      widely exists in plants. A handful of ALOG members have been functionally
      characterized, suggesting their roles as key developmental regulators. However,
      the evolutionary scenario of this gene family during the diversification of plant
      species remains largely unclear. METHODS: Here, we isolated seven ALOG genes from
      Torenia fournieri and phylogenetically analyzed them with different ALOG members
      from representative plants in major taxonomic clades. We further examined their
      gene expression patterns by RT-PCR, and regarding the protein subcellular
      localization, we co-expressed the candidates with a nuclear marker. Finally, we
      explored the functional diversification of two ALOG members, TfALOG1 in euALOG1
      and TfALOG2 in euALOG4 sub-clades by obtaining the transgenic T. fournieri
      plants. RESULTS: The ALOG gene family can be divided into different lineages,
      indicating that extensive duplication events occurred within eudicots, grasses
      and bryophytes, respectively. In T. fournieri, seven TfALOG genes from four sub
      clades exhibit distinct expression patterns. TfALOG1-6 YFP-fused proteins were
      accumulated in the nuclear region, while TfALOG7-YFP was localized both in
      nuclear and cytoplasm, suggesting potentially functional diversification. In the
      35S:TfALOG1 transgenic lines, normal development of petal epidermal cells was
      disrupted, accompanied with changes in the expression of MIXTA-like genes. In
      35S:TfALOG2 transgenic lines, the leaf mesophyll cells development was abnormal,
      favoring functional differences between the two homologous proteins.
      Unfortunately, we failed to observe any phenotypical changes in the TfALOG1 knock
      out mutants, which might be due to functional redundancy as the case in
      Arabidopsis. CONCLUSION: Our results unraveled the evolutionary history of ALOG
      gene family, supporting the idea that changes occurred in the cis regulatory
      and/or nonconserved coding regions of ALOG genes may result in new functions
      during the establishment of plant architecture.

PMID- 30236063
TI  - Geriatric palliative care: a view of its concept, challenges and strategies.
AB  - In aging societies, the last phase of people's lives changes profoundly,
      challenging traditional care provision in geriatric medicine and palliative care.
      Both specialties have to collaborate closely and geriatric palliative care (GPC)
      should be conceptualized as an interdisciplinary field of care and research based
      on the synergies of the two and an ethics of care.Major challenges characterizing
      the emerging field of GPC concern (1) the development of methodologically
      creative and ethically sound research to promote evidence-based care and
      teaching; (2) the promotion of responsible care and treatment decision making in
      the face of multiple complicating factors related to decisional capacity,
      communication and behavioural problems, extended disease trajectories and complex
      social contexts; (3) the implementation of coordinated, continuous care despite
      the increasing fragmentation, sectorization and specialization in health
      care.Exemplary strategies to address these challenges are presented: (1) GPC
      research could be enhanced by specific funding programs, specific patient
      registries and anticipatory consent procedures; (2) treatment decision making can
      be significantly improved using advance care planning programs that include
      adequate decision aids, including those that address proxies of patient who have
      lost decisional capacity; (3) care coordination and continuity require multiple
      approaches, such as care transition programs, electronic solutions, and
      professionals who act as key integrators.

PMID- 30236064
TI  - Epileptic spasms in PPP1CB-associated Noonan-like syndrome: a case report with
      clinical and therapeutic implications.
AB  - BACKGROUND: Noonan syndrome-like disorder with loose anagen hair-2 (NSLH2) is an
      extremely rare disease caused by a heterozygous mutation in the PPP1CB gene on
      chromosome 2p23. The syndrome causes not only numerous dysmorphic features but
      also hypotonia, developmental delay, and even intellectual disability. We report
      the first case of NSLH2 in Asia and the 16th in the world. Moreover, the first
      case of PPP1CB-related infantile spasms. The clinical and therapeutic
      significance is outlined in this paper. CASE PRESENTATION: We found a male infant
      presented with severe intractable epileptic spasms. Although certain clinical
      features of somatic dysmorphism were noted, numerous laboratory and neuroimaging
      studies failed to identify the cause. To determine the underlying etiology, whole
      exome sequencing was conducted. We identified a de novo heterozygous mutation,
      NM_206876.1: c.548A > C (p.Glu183Ala), in the PPP1CB gene. His seizures were
      almost refractory to conventional antiepileptic drugs but relative seizure
      control was eventually achieved with a ketogenic diet. CONCLUSION: This result
      expands the clinical spectrum of NSLH2 and strengthens the association between
      the PPP1CB gene and epileptic seizures. Furthermore, we suggest that the
      ketogenic diet can offer seizure reduction in particular drug-resistant epilepsy
      syndromes. Additional studies are warranted to clarify the pathogenic mechanisms
      underlying this PPP1CB mutation in epileptic seizures.

PMID- 30236065
TI  - Switching iron sucrose to ferric carboxymaltose associates to better control of
      iron status in hemodialysis patients.
AB  - BACKGROUND: Although the efficacy of iron sucrose (IS) and ferric carboxymaltose
      (FCM) in treating anemia in hemodialysis (HD) patients has been studied
      individually, a comparison of these two intravenous iron formulations has not yet
      been performed in HD patients. METHODS: We performed a retrospective audit on
      records of 221 stable HD patients from different HD centers in the Netherlands,
      who were switched from IS to FCM on a 1:1 ratio. To assess the effect of the
      switch on iron status parameters, data from 3 time points before and 3 time
      points after the switch were analyzed using linear mixed effects models.
      Subanalyses were done in 2 subgroups of patients anemic or iron deficient at
      baseline. RESULTS: Hemoglobin increased in all groups (anemic [1.4 g/dL, P <
      0.001] iron deficient [0.6 g/dL, P < 0.001]), while the weekly iron dose was
      significantly lower when patients received FCM compared to IS (48 vs 55 mg/week,
      P = 0.04). Furthermore, serum ferritin and transferrin saturation increased in
      all groups (anemic [64 MUg/L, 5.0%, P < 0.001] iron deficient [76 MUg/L, 3.6%, P
      < 0.001]). Finally, the darbepoetin alpha dose decreased significantly in all
      groups (anemic [- 16 MUg/wk., P = 0.01] iron deficient [- 11 MUg/wk., P <
      0.001]). CONCLUSIONS: In this real-life study in HD patients, a switch from IS to
      FCM resulted in an improvement of iron status parameters despite a lower weekly
      dose of FCM. Furthermore, the ESA dose was reduced during FCM, while hemoglobin
      levels increased.

PMID- 30236066
TI  - Urological dysfunctions in patients with Parkinson's disease: clues from clinical
      and non-invasive urological assessment.
AB  - BACKGROUND: Autonomic nervous system dysfunction, common in patients with
      Parkinson's disease (PD), causes significant morbidity and it is correlated with
      poor quality of life. To assess frequency of urinary symptoms in patients with
      PD, without conditions known to interfere with urinary function. METHODS: Non
      demented PD patients were consecutively enrolled from the outpatients clinic of
      our department. Scales investigating motor and non-motor symptoms were carried
      out. Evaluation of urinary dysfunctions was carried out using the AUTonomic Scale
      for Outcomes in Parkinson's disease (SCOPA-AUT) questionnaire. Patients underwent
      noninvasive urological studies (nUS), including uroflowmetry and ultrasound of
      the urinary tract. RESULTS: Forty-eight (20 women, 42%) out of 187 PD patients
      met the inclusion criteria and were enrolled in the study. Mean SCOPA-AUT score
      was 14.1 +/- 6.9 (urinary symptoms subscore 5.2 +/- 3.8). Among those evaluated
      by the SCOPA-AUT scale, the urinary symptoms were among the most common
      complaints (93.8%). At nUS mean maximum flow rate (Qmax) was 17.9 +/- 9.1 ml/s,
      and mean postvoid residual (PVR) urine volume was 24.4 +/- 44.1 ml. Ultrasound
      investigation documented prostate hypertrophy in 12 male patients (42.8%).
      Urinary items of the SCOPA-AUT (SCOPA-U subscore) correlated with measures of
      disease severity only in female patients. CONCLUSION: Urinary symptoms and
      abnormal findings in nUS are common in PD. Though nigrostriatal degeneration
      might be responsible for urinary symptoms also in the early-intermediate stage of
      the disease, when urinary dysfunction occurs other medical conditions need to be
      excluded.

PMID- 30236067
TI  - A randomized comparison of three data collection models for the measurement of
      parent experiences with diabetes outpatient care.
AB  - BACKGROUND: The objective of this study was to compare three data collection
      methods for the measurement of parent experiences with hospital outpatient care
      for child and adolescent diabetes, based on a randomised national trial in Norway
      involving both pen-and-paper and electronic response options. METHODS: The sample
      frame was patients registered in the Norwegian Childhood Diabetes Registry.
      Parents of patients were randomised into the following groups (n = 2606): group
      A, who were posted questionnaires with only a pen-and-paper response option (n =
      859); group B, who were posted questionnaires with both an electronic and a pen
      and-paper response option (n = 886); and group C, who were posted questionnaires
      with only an electronic response option (n = 861). The three groups were compared
      on response rate, background variables about respondents, main study results and
      survey costs. Statistical analysis included logistic regression to test group
      differences in response probabilities and multilevel linear regression to test
      differences in parent experiences. RESULTS: The response rate was 61.8% for group
      A, 62.4% for group B and 41.6% for group C. The probability of answering was
      significantly higher for group A (OR = 2.3, p < 0.001) and B (OR = 2.3, p <
      0.001) compared to group C. Respondent age, gender, education, living with the
      child and the degree of participation in consultations did not differ
      significantly between the three groups. Group differences in parent-reported
      experiences were small, varying from 1.0 (equipment and doctor contact) to 2.4
      (outcome), on a scale from 0 to 100. Only one of 18 group differences was
      significant: the mixed group had significantly higher score than the electronic
      group on the organization scale (p < 0.05). The total cost of the electronic
      model was less than half the cost of the other models, and cost per response was
      5.1 euros for the electronic model compared to 8.2 euros for group A and 7.6
      euros for group B. CONCLUSIONS: The models with pen-and paper questionnaire
      included had more than 20% higher response rate than the model with an electronic
      only response option. Background variables and parent-reported experiences were
      similar between the three groups, and the electronic model was the more cost
      effective model.

PMID- 30236069
TI  - Evaluation of the efficacy of amplitude-integrated electroencephalography in the
      screening of newborns with metabolic disorder admitted to the NICU.
AB  - BACKGROUND: Neonate patients with metabolic disorder show encephalopathy and
      seizures that may lead to morbidity and mortality. Thus rapid detection and
      treatment of these patients is necessary. Although Amplitude-integrated
      electroencephalography (aEEG) has been used for more than a decade in the
      evaluation of infants with encephalopathy but has not been used in the assessment
      of neonates suffering from metabolic disorders. In this study, we tried to
      determine the efficacy of aEEG as an easily available diagnostic tool in the
      diagnosis of neonates with metabolic diseases. METHODS: All cases which admitted
      to the Neonatal Intensive Care Unit (NICU) of the Children's Medical Center
      during a one-year period were enrolled. aEEG recordings were obtained by
      installing 4 electrodes on the infant's head by a trained nurse and aEEG was
      recorded for at least 24 h with a description of the whole tracing. Clinical
      information, final outcome and questionnaires, including patient information:
      symptoms of the disease, gender, age, duration of hospitalization and the type of
      the metabolic disease were recorded in details. The obtained data was analyzed
      with the Spss24 software. RESULTS: Only 3 (two girl and one boy) out of 29 aEEGs
      recordings were abnormal; other patients showed normal aEEGs. The most common
      clinical and neurological manifestations were seizure (34.5%), hypotonia (31%),
      and mortality rate was 10.3%. There was no significant correlation between aEEG
      findings and gender, age, type of disease, laboratory tests findings and positive
      family history. CONCLUSIONS: Although it has been shown that EEG has a diagnostic
      value in metabolic diseases, there has been no study on the efficacy of aEEG to
      evaluate neonates with metabolic diseases. But good accessibility and easy of
      working with aEEG, promote a tendency to use this procedure as screening tool for
      metabolic diseases. The current study about aEEG monitoring in these patients,
      while limited, can be used as a pilot study for further research on this topic.
      Therefore, a correct judgment in this field requires administration of aEEG on a
      larger population of neonates with metabolic diseases.

PMID- 30236068
TI  - Relation of multi-marker panel to incident chronic kidney disease and rapid
      kidney function decline in African Americans: the Jackson Heart Study.
AB  - BACKGROUND: Few investigations have evaluated the incremental usefulness of
      multiple biomarkers representing varying physiological pathways for predicting
      risk of renal outcomes in African Americans. DESIGN, SETTING, PARTICIPANTS, AND
      MEASUREMENTS: We related a multi-marker panel to incident chronic kidney disease
      (CKD) and rapid kidney function decline (RKFD) in 2813 Jackson Heart Study
      participants without prevalent CKD at exam 1 (2000-2004) and with complete assays
      at exam 1 for 9 biomarkers: adiponectin, aldosterone, B-natriuretic peptide
      [BNP], cortisol, high sensitivity C-reactive protein (hsCRP), endothelin,
      homocysteine, plasma renin activity and mass. Incident CKD was defined as
      estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at exam 3 while
      RKFD was defined as eGFR >=30% loss between exams 1 and 3 (8.2 median years). We
      employed multiple logistic regression model to describe association between the
      panel and incident CKD and RKFD and used backward elimination strategy to
      estimate the most parsimonious biomarker model while controlling for conventional
      risk factors. RESULTS: The multi-marker panel predicted the risk for both
      incident CKD (odds ratios [OR], 2.72; 95% confidence intervals [CI], 1.63, 4.56;
      P = 0.001) and RKFD (2.61; 95% CI, 1.67, 4.08; P < 0.001). Per standard deviation
      increase in log biomarker concentrations were significantly (multivariable
      adjusted odds ratios, [95% confidence interval], p-value) associated with
      incident CKD: plasma adiponectin (1.24 [1.07, 1.44], p = 0.005) and leptin (1.3
      [1.06, 1.61], p = 0.011), and with RKFD: plasma adiponectin (1.22 [1.06, 1.40], p
      = 0.006); hsCRP (1.17 [1.01, 1.36], p = 0.031) and aldosterone (0.85 [0.74,
      0.96], p = 0.012). Moderate levels (3rd quartile) of aldosterone were inversely
      associated with incident CKD (0.54 [0.35, 0.82], p = 0.004) while leptin was
      associated with RKFD (1.64 [1.10, 2.44], p = 0.015). Biomarkers improved CKD risk
      prediction (P = 0.003) but not RKFD risk prediction (P = 0.10). CONCLUSION: In
      this community-based sample of African Americans, a multi-marker panel added only
      moderate predictive improvement compared to conventional risk factors.

PMID- 30236070
TI  - Change in alkaline phosphatase activity associated with intensive care unit and
      hospital length of stay in patients with septic acute kidney injury on continuous
      renal replacement therapy.
AB  - BACKGROUND: Evidence suggests that alkaline phosphatase attenuates inflammatory
      response in sepsis by lipopolysaccharide detoxification and adenosine
      triphosphate dephosphorylation. We sought to determine changes in alkaline
      phosphatase (AP) activity during septic acute kidney injury (AKI) and clinical
      parameters associated with AP activity. METHODS: In this retrospective study, we
      investigated baseline (when initiating CRRT) and follow-up AP activity on day 3,
      and associated outcomes in patients who underwent continuous renal replacement
      therapy (CRRT) due to septic AKI. RESULTS: We analyzed the baseline AP activity
      of 155 patients and day 3 AP activity in 123 patients. Baseline AP activity was
      not associated with renal or inflammatory biomarkers, or outcomes. It did not
      significantly differ between the 75 survivors and 80 non-survivors (p = 0.155).
      AP activity was higher on day 3 than at baseline (105 U/L [interquartile range,
      79-156] vs 90 U/L [interquartile range, 59-133]). In particular, liver and bone
      isoforms increased significantly (p < 0.05), but intestine isoforms did not reach
      statistical significance (p = 0.367). In addition, day 3 AP activity showed a
      weak correlation with length of ICU stay (r = 0.213, p = 0.018) and length of
      hospital stay (r = 0.216, p = 0.017), but not with survival (r = - 0.035, p =
      0.698). CONCLUSION: Endogenous AP activity significantly increased in patients
      with septic AKI. However, neither baseline nor follow-up AP activity was
      associated with survival.

PMID- 30236071
TI  - Prevalence and predictors of vitamin D-deficiency in frail older hospitalized
      patients.
AB  - BACKGROUND: Vitamin D deficiency is known to be highly prevalent in older
      persons. However, the prevalence in the subgroup of frail older hospitalized
      patients is not clear. We sought to investigate the prevalence and predictors of
      vitamin D deficiency in frail older hospitalized patients. METHODS: 217
      consecutively geriatric hospitalized patients with routine measurements of 25
      hydroxyvitamin D [25 (OH)D] at hospital admission were analyzed retrospectively,
      including information of previous vitamin D supplementation and the geriatric
      assessment. Serum 25 (OH)D concentrations < 20 ng/ml and between 20 and 29.99
      ng/ml were classified as deficient and insufficient, respectively, whereas
      concentrations >=30 ng/ml were considered as desirable. A stepwise binary
      logistic regression model was performed to assess the simultaneous effects of
      age, gender and geriatric assessments on the prevalence of low vitamin D
      concentration. RESULTS: Mean age of the cohort was 81.6 +/- 8.0 years (70.0%
      females). Mean serum 25(OH)D was 12.7 +/- 12.9 ng/ml. Of 167 (77%) subjects
      without known previous vitamin D supplementation, only 21 (12.6%) had serum
      concentrations >=20 ng/ml and only 8 (4.2%) had desirable serum concentrations
      >=30 ng/ml. In total population, 146 (87.4%) participants were vitamin D
      deficient. Despite vitamin D supplementation, 22 of 50 participants (44.0%) were
      vitamin D deficient and only 19 (38.0%) had desirable concentrations of >=30
      ng/ml. In a stepwise logistic regression analysis, only previous intake of
      vitamin D supplementation and high Geriatric Depression Scale score (GDS-15) were
      significantly associated with vitamin D deficiency. CONCLUSIONS: In the group of
      frail older hospitalized patients without previous vitamin D supplementation, the
      prevalence of inadequate vitamin D concentrations is extremely high. Therefore,
      usefulness of the routine measurement of vitamin D status before initiating of
      supplementation appears to be questionable in this patient group.

PMID- 30236072
TI  - Evaluation of health status and its predictor among university staff in Nigeria.
AB  - BACKGROUND: Hypertension, diabetes mellitus and obesity share some
      characteristics in relation to diagnosis, management, and prevention. Overweight,
      obesity and waist-hip ratio (WHR) are associated with increased risk for
      development of diabetes and hypertension. Surveillance and regular screening
      exercises are essential in control and prevention of overweight, obesity,
      diabetes and hypertension. There is limited literature that reported on these
      health status parameters among university staff in low- and middle-income
      countries such as Nigeria. It is currently unclear whether Nigerian have a high
      or low proportion of metabolic risk factors. Therefore, the study aims to examine
      health status parameters and their predictors among university staff in Nigeria.
      METHODS: The study used a cross-sectional descriptive design. Data were collected
      from 280 university staff in Nigeria. A self-administered questionnaire with
      sections for sociodemographic data and physical assessment was used to gather
      information from the participants. Data were analysed using the Statistical
      Package for Social Science (IBM-SPSS version 25). Univariable and multivariable
      logistic regression was conducted to explore the association between predictors
      and health status parameters of the participants. RESULT: The response rate was
      87.5%. University staff had mean systolic blood pressure of 132.04 mmHg +/- 19.20
      mmHg, diastolic blood pressure of 78.11 mmHg +/- 10.81 mmHg, body mass index of
      27.74 +/- 5.22, waist-hip ratio of 0.88 +/- 0.68 and random blood sugar of 98.65
      +/- 21.30 mg/dL. Predictors of high blood pressure were age (adjusted odds ratio
      [aOR] = 1.10, CI 95%: [1.05-1.14]) and gender (aOR = 0.5, CI 95%: [0.8-0.9]) and
      predictors of body mass index were gender (aOR = 2.3, CI 95%: [1.3-4.2]) and
      religion (aOR = 0.3, CI 95%: [0.2-0.7]). Gender and age had statistically
      significant association with waist-hip ratio and random blood sugar respectively.
      CONCLUSION: The prevalence rates of high blood pressure and random blood sugar;
      overweight, obesity and risk WHR are on the increase compared to previous
      studies. Lifestyle modification, organized and explicit health campaigns coupled
      with regular screening and surveillance will contribute to the prevention and
      control of noncommunicable diseases.

PMID- 30236073
TI  - Identification of a novel TSC2 c.3610G > A, p.G1204R mutation contribute to
      aberrant splicing in a patient with classical tuberous sclerosis complex: a case
      report.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder
      characterized by hamartomas in any organ systems. Mutations in the TSC1 or TSC2
      gene lead to the dysfunction of hamartin or tuberin proteins, which cause
      tuberous sclerosis complex. CASE PRESENTATION: We describe the clinical
      characteristics of patients from a Chinese family with tuberous sclerosis complex
      and analyze the functional consequences of their causal genetic mutations. A
      novel heterozygous mutation (c.3610G > A) at the last nucleotide of exon 29 in
      TSC2 was identified. On the protein level, this variant was presumed to be a
      missense mutation (p.Gly1204Arg). However, the splicing assay revealed that this
      mutation also leads to the whole TSC2 exon 29 skipping, besides the wild-type
      transcript. The mutated transcript results in an in-frame deletion of 71 amino
      acids (p.Gly1133_Thr1203del) and its ratio with the normal splice product is of
      about 44:56. CONCLUSIONS: The novel c.3610G > A TSC2 mutation was identified in
      association with tuberous sclerosis complex. And it was proven to code both for a
      missense-carrying transcript (56%), and for an isoform lacking exon 29 (44%).

PMID- 30236074
TI  - Mutation m.15923A>G in the MT-TT gene causes mild myopathy - case report of an
      adult-onset phenotype.
AB  - BACKGROUND: Only five patients have previously been reported to harbor mutations
      in the MT-TT gene encoding mitochondrial tRNA threonine. The m.15923A > G
      mutation has been found in three severely affected children. One of these
      patients died within days after birth and two had a phenotype of myoclonic
      epilepsy with ragged red fibers (MERRF) in early childhood. We have now found the
      mutation in an adult patient with mild myopathy. CASE PRESENTATION: The patient
      is a 64-year-old Finnish man, who developed bilateral ptosis, diplopia and
      exercise intolerance in his fifties. Family history was unremarkable. Muscle
      histology showed cytochrome c-oxidase (COX) negative and ragged red fibres. The
      m.15923A > G mutation heteroplasmy was 33% in the skeletal muscle and 2% in
      buccal epithelial cells. The mutation was undetectable in the blood. Single-fibre
      analysis was performed and COX-negative fibres had a substantially higher
      heteroplasmy of 92%, than the normal fibres in which it was 43%. CONCLUSIONS: We
      report the fourth patient with m. 15923A > G and with a remarkably milder
      phenotype than the previous three patients. Our findings and recent biochemical
      studies suggest that the mutation m.15923A > G is a definite disease-causing
      mutation. Our results also suggest that heteroplasmy of the m.15923A > G mutation
      correlates with the severity of the phenotype. This study expands the catalog of
      the phenotypes caused by mutations in mtDNA.

PMID- 30236076
TI  - Endometriosis-associated recto-sigmoid cancer: a case report.
AB  - BACKGROUND: Endometriosis is a relatively common condition in women of
      reproductive age. Malignant transformation of intestinal endometriosis is a very
      rare event. We report a case in which a patient with a history of endometriosis
      underwent surgery for malignant intestinal endometriosis. CASE PRESENTATION: A 55
      year-old woman complained of rectorrhagia and intermittent abdominal pain. A
      neoplasm was revealed by colonoscopy, CT scan and F18-FDG PET/CT of the recto
      sigmoidal colon. The patient underwent a rectal anterior resection, hysterectomy
      and bilateral salpingo-oophorectomy for treatment. According to the histological
      and immunohistochemical presentation, the diagnosis of endometriosis-associated
      recto-sigmoid cancer was confirmed. The patient was treated with adjuvant
      chemotherapy for 6 months. During the follow-up appointment 22 months later,
      there was clinical and radiographic evidence of recurrence in the rectum. The
      patient received chemotherapy again and will receive another surgery after two
      more cycles of chemotherapy. CONCLUSION: We report a case of malignant intestinal
      endometriosis. Although there is no standard therapy for malignant intestinal
      endometriosis due to the rarity of this disease, surgery and adjuvant
      chemotherapy seemed to be rational. This case indicates that local recurrence may
      be a common situation after standard therapy.

PMID- 30236075
TI  - Factors associated with favourable outcome in large hemispheric infarctions.
AB  - BACKGROUND: Large hemispheric infarction (LHI) is a devastating condition with
      high mortality and poor functional outcome in most conservatively treated
      patients. The purpose of this study was to explore factors associated with
      favorable outcome in patients with LHI. METHODS: We prospectively enrolled
      consecutive patients with LHI. Favorable outcome was defined as a modified Rankin
      Scale (mRS) score of 0 to 3 at 90 days. Multivariate logistic regression analysis
      was employed to identify the independent factors associated with favorable
      outcome. RESULTS: Two hundred fifty-six cases with LHI were identified: 41
      (16.0%) died during hospitalization, 94 (36.7%) died at 3 month, and 113 (44.1%)
      survived with favorable outcome at day 90. Compared with patients with
      unfavorable outcome, the favorable cases were younger (55.8 +/- 14.7 vs. 66.2 +/-
      14.1), had less history of hypertension (38.9% vs. 59.3%), lower baseline NIHSS
      score (median NIHSS score 11 vs. 17), lower blood pressure on admission (systolic
      134.7 +/- 24.9 vs. 145.1 +/- 26.1 mmHg; diastolic 80.2 +/- 14.9 vs. 86.9 +/- 16.2
      mmHg; respectively), lower level of baseline serum glucose (7.2 +/- 3.3 vs. 8.2
      +/- 3.3 mmol/L), a lower frequency of stroke-related complications (55.8% vs.
      91.4%), more use of antiplatelets (93.8% vs. 57.1%) and statins (46.9% vs. 25.7%)
      in the acute phase of stroke, but less use of osmotic agents (69.9% vs. 89.3%),
      mechanical ventilation (1.8% vs. 20.0%) or decompressive hemicraniectomy (1.8%
      vs. 15.7%). Multivariable analysis identified the following factors associated
      with favorable outcome: age (odds ratio, OR 0.95, 95% confidence interval [CI]
      0.92-0.98, p < 0.001), baseline NIHSS score (OR 0.90, 95% CI 0.84-0.96, p =
      0.002), statins used in acute phase (OR 2.49, 95% CI 1.10-5.65, p = 0.029), brain
      edema (OR 0.05, 95% CI 0.01-0.21, p < 0.001) and pneumonia (OR 0.42, 95% CI 0.19
      0.93, p = 0.032). CONCLUSION: More than one third of patients with LHI have
      relatively favorable clinical outcomes at 90 days. Younger age, lower baseline
      NIHSS score, absence of brain edema and pneumonia, and statins used in the acute
      phase were associated with favorable outcome of patients with LHI at 90 days.

PMID- 30236077
TI  - The psychometric properties of the Childhood Health Assessment Questionnaire
      (CHAQ) in children with cerebral palsy.
AB  - BACKGROUND: The evaluation of children with cerebral palsy (CP) focuses on
      activity level measurement to examine the effect of health-care interventions on
      their physical functioning in the home, school, and community settings. This
      study aimed to identify the psychometric properties of the Korean version of the
      Childhood Health Assessment Questionnaire (CHAQ) by applying the Rasch model. The
      use of the Rasch model has an advantage in that item characteristic curve
      estimation is not affected by the characteristics of subject groups. METHODS:
      Data were collected from 65 children with CP aged 75-190 months using the Korean
      version of the CHAQ. Response data were analyzed according to the Rasch model,
      and item fitness and difficulty and the appropriateness and reliability of the
      rating scale were evaluated. RESULTS: Among the 30 items of the Korean version of
      the CHAQ, two items (nail-cutting and opening a bottle cap that was already
      opened) were shown to be misfit items with low fitness. The analysis results for
      item difficulty indicated the requirement for modification of item difficulty,
      pointing out the need for the addition of question items with both higher and
      lower difficulty. The use of 4-point rating scale in the evaluation questionnaire
      was shown to be appropriate. With respect to analysis outcomes, the subjects'
      separation reliability value and separation index were 0.97 and 5.92,
      respectively. In contrast, the separation reliability value and separation index
      for the question items were 0.95 and 4.51, respectively. CONCLUSIONS: The results
      of this study suggest the need for the modification of item fitness and
      difficulty. The psychometric properties of the Korean version of the CHAQ were
      identified using the item response theory-based Rasch analysis.

PMID- 30236078
TI  - Use of 18F-sodium fluoride bone PET for disability evaluation in ankle trauma: a
      pilot study.
AB  - BACKGROUND: There are no objective and accurate rating tools for permanent
      impairment of traumatized ankles. The purpose of this study is to assess the role
      of 18F-Sodium fluoride (18F-NaF) positron emission tomography-computed tomography
      (PET/CT) bone scans in evaluating patients with limited ankle range of motion
      (ROM) after trauma. METHODS: 18F-NaF PET/CT was performed in 121 patients (75
      men, 46 women; mean age: 45.8) who had ROM < 70% of normal after trauma affecting
      ankles. Metabolic target volume (MTV), the sum of voxels with standardized uptake
      value (SUV) > 2.5 was automatically obtained from the 3D volume that included the
      ankle joint. The maximum & mean SUV (SUVmax & SUVmean), and the total lesion
      activity (TLA) were measured. RESULTS: The median period from injury to
      performing 18F-NaF PET/CT was 290 days. The causes of injury were as follows:
      fracture (N = 95), Achilles tendon rupture (N = 12), and ligament injury (N =
      12). Hot uptake in the ankle was seen in 113 of 121 patients. The fracture group
      had higher SUVmax, SUVmean, and TLA values than the non-fracture group. More
      limited ROM correlated with higher hot-uptake parameters (SUVmax, SUVmean, TLA).
      In subgroup analysis, the same correlations were present in the fracture, but not
      in the non-fracture group. CONCLUSIONS: 18F-NaF PET/CT can provide considerable
      information in impairment evaluations of limited ankle ROM, particularly in
      fracture around the ankle. Thus, 18F-NaF bone PET/CT may provide an additional
      option as an objective imaging tool in disability assessment after ankle injury.

PMID- 30236080
TI  - Perinatal death beyond 41 weeks pregnancy: an evaluation of causes and
      substandard care factors as identified in perinatal audit in the Netherlands.
AB  - BACKGROUND: Late- and postterm pregnancy are associated with adverse perinatal
      outcomes, like perinatal death. We evaluated causes of death and substandard care
      factors (SSFs) in term and postterm perinatal death. METHODS: We used data from
      the Perinatal Audit Registry of the Netherlands (PARS). Women with a term
      perinatal death registered in PARS were stratified by gestational age into early
      /full-term (37.0-40.6) and late-/postterm (>=41.0 weeks) death. Cause of death
      and SSFs >=41 weeks were scored and classified by the local perinatal audit
      teams. RESULTS: During 2010-2012, 947/479,097 (0.21%) term deaths occurred, from
      which 707 cases (75%) were registered and could be used for analyses. Five
      hundred ninety-eight early-/full-term and 109 late-/postterm audited deaths were
      registered in the PARS database. Of all audited cases of perinatal death in the
      PARS database, 55.2% in the early-/fullterm group occurred antepartum compared to
      42.2% in the late-/postterm group, while intrapartum death occurred in 7.2% in
      the early-/full-term group compared to 19.3% in the late-/postterm group in the
      audited cases from the PARS database. According to the local perinatal audit, the
      most relevant causes of perinatal death >=41 weeks were antepartum asphyxia
      (7.3%), intrapartum asphyxia (9.2%), neonatal asphyxia (10.1%) and placental
      insufficiency (10.1%). In the group with perinatal death >=41 weeks there was
      >=1SSF identified in 68.8%. The most frequent SSFs concerned inadequate
      cardiotocography (CTG) evaluation and/or classification (10.1%), incomplete
      registration or documentation in medical files (4.6%) or inadequate action on
      decreased foetal movements (4.6%). CONCLUSIONS: In the Netherlands Perinatal
      Audit Registry, stillbirth occurred relatively less often antepartum and more
      often intrapartum in pregnancies >=41 weeks compared to pregnancies at 37.0-40.6
      weeks in the audited cases from the PARS database. Foetal, intrapartum and
      neonatal asphyxia were identified more frequently as cause of death in
      pregnancies >=41 weeks. The most identified SSFs related to death in pregnancies
      >=41 weeks concerned inadequate CTG monitoring (evaluation, classification,
      registration or documentation) and inadequate action on decreased foetal
      movements.

PMID- 30236081
TI  - Use of rituximab as an induction therapy in anti-glomerular basement-membrane
      disease.
AB  - BACKGROUND: Anti-glomerular basement-membrane (anti-GBM) disease (or Goodpasture
      disease) is characterized by severe kidney and lung involvement. Prognoses have
      improved with treatments that combine plasma exchange and immunosuppressive
      drugs. However, patients with severe renal involvement can have poor renal
      outcomes and cyclophosphamide can cause significant complications. Anti-GBM
      antibodies have a direct pathogenic effect on the disease: thus, therapeutics
      that can decrease their production, such as rituximab, could be a good
      alternative. METHODS: The medical files of five patients that had received
      rituximab as a first-line therapy (instead of cyclophosphamide), plus plasma
      exchange and steroids, were reviewed. All patients had severe disease
      manifestations. RESULTS: Four patients required dialysis at diagnosis and
      remained dialysis-dependent over the mean follow-up of 15 months. Three patients
      had pulmonary involvement, but recovered even though mechanical ventilation was
      required. Anti-GBM antibodies became rapidly undetectable in all patients. One
      infectious and two hematological complications were observed. CONCLUSIONS: We
      report the outcomes of five patients with Goodpasture disease and treated with
      rituximab as a first-line treatment. This strategy was effective at treating
      pulmonary manifestations and was associated with a good biological response with
      no major serious adverse events. However, renal outcomes were not significantly
      improved.

PMID- 30236079
TI  - A new promising way of maintenance therapy in advanced ovarian cancer: a
      comparative clinical study.
AB  - BACKGROUND: There is an urgent need for more novel and efficacious therapeutic
      agents and strategies for the treatment of ovarian cancer - one of the most
      formidable female malignancies. These approaches should be based on comprehensive
      understanding of the pathobiology of this cancer and focused on decreasing its
      recurrence and metastasis. The aim of this study was to evaluate the efficacy of
      five-year maintenance therapy with indole-3-carbinol (I3C) as well as I3C and
      epigallocatechin-3-gallate (EGCG) conducted before, during, and after combined
      treatment compared with combined treatment alone in advanced ovarian cancer.
      METHODS: Patients with stage III-IV serous ovarian cancer were assigned to
      receive combined treatment plus I3C (arm 1), combined treatment plus I3C and EGCG
      (arm 2), combined treatment plus I3C and EGCG plus long-term platinum-taxane
      chemotherapy (arm 3), combined treatment alone without neoadjuvant platinum
      taxane chemotherapy (control arm 4), and combined treatment alone (control arm
      5). Combined treatment included neoadjuvant platinum-taxane chemotherapy,
      surgery, and adjuvant platinum-taxane chemotherapy. The primary endpoint was
      overall survival (OS). Secondary endpoints were progression-free survival (PFS)
      and rate of patients with recurrent ovarian cancer with ascites after combined
      treatment. RESULTS: After five years of follow-up, maintenance therapy
      dramatically prolonged PFS and OS compared to control. Median OS was 60.0 months
      (95% CI: 58.0-60.0 months) in arm 1, 60.0 months (95% CI: 60.0-60.0 months) in
      arms 2 and 3 while 46.0 months (95% SI: 28.0-60.0 months) in arm 4, and 44.0
      months (95% SI: 33.0-58.0 months) in arm 5. Median PFS was 39.5 months (95% SI:
      28.0-49.0 months) in arm 1, 42.5 months (95% SI: 38.0-49.0 months) in arm 2, 48.5
      months (95% SI: 39.0-53.0 months) in arm 3, 24.5 months (95% SI: 14.0-34.0
      months) in arm 4, 22.0 months (95% SI: 15.0-26.0 months) in arm 5. The rate of
      patients with recurrent ovarian cancer with ascites after combined treatment was
      significantly less in maintenance therapy arms compared to control. CONCLUSIONS:
      Long-term usage of I3C and EGCG may represent a new promising way of maintenance
      therapy in advanced ovarian cancer patients, which achieved better treatment
      outcomes. TRIAL REGISTRATION: Retrospectively registered with ANZCTR number:
      ACTRN12616000394448 . Date of registration: 24/03/2016.

PMID- 30236082
TI  - Renal association commentary on the KDIGO (2017) clinical practice guideline
      update for the diagnosis, evaluation, prevention, and treatment of CKD-MBD.
AB  - This report comments on the relevance and utility of the recently published
      (2017) KDIGO Clinical Practice Guideline Update for the diagnosis, evaluation,
      prevention and treatment of mineral bone disease in patients with chronic kidney
      disease (CKD-MBD) with respect to UK clinical practice. This document replaces
      all previously published Renal Association guidelines on the topic.

PMID- 30236084
TI  - The moderating roles of bedtime activities and anxiety/depression in the
      relationship between attention-deficit/hyperactivity disorder symptoms and sleep
      problems in children.
AB  - BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) often
      experience sleep problems, but the comorbidity mechanism has not been
      sufficiently studied. This study aimed to determine the comorbidity of ADHD
      symptoms and sleep problems as well as the moderating effects of bedtime
      activities and depression/anxiety symptoms on the relationship between ADHD
      symptoms and sleep problems. METHODS: We recruited 934 primary students from
      third to fifth grade and their parents by stratified random sampling from three
      primary schools in Shanghai, China. This study used parent-reported versions of
      the ADHD Rating Scale-IV, Children's Sleep Habits Questionnaire, and Achenbach
      Child Behavior Checklist. We used hierarchical linear regression analysis to
      clarify the moderating effects of bedtime activities and depression/anxiety
      symptoms. RESULTS: We found that children with more ADHD symptoms had shorter
      sleep durations and more sleep problems on weekdays. Screen time before bedtime
      strengthened the relationship between ADHD symptoms and sleep-disordered
      breathing. Children with more screen time were more likely to have sleep onset
      delay, while those with less screen time had more sleep onset problems with
      increasing ADHD symptoms. The high bedtime eating group experienced more night
      waking with increasing ADHD symptoms compared with the low bedtime eating group.
      Anxiety/depression exacerbated total sleep problems and further interacted with
      ADHD symptoms to predict sleep length and sleep duration problems. CONCLUSIONS:
      Bedtime activities and emotional problems had important moderating effects on the
      relationship between ADHD symptoms and sleep problems. These findings indicate
      that appropriate bedtime management and emotional management may reduce sleep
      problems and improve sleep duration for children with ADHD symptoms.

PMID- 30236083
TI  - A review of sex-related differences in colorectal cancer incidence, screening
      uptake, routes to diagnosis, cancer stage and survival in the UK.
AB  - BACKGROUND: Colorectal cancer (CRC) is an illness strongly influenced by sex and
      gender, with mortality rates in males significantly higher than females. There is
      still a dearth of understanding on where sex differences exist along the pathway
      from presentation to survival. The aim of this review is to identify where
      actions are needed to improve outcomes for both sexes, and to narrow the gap for
      CRC. METHODS: A cross-sectional review of national data was undertaken to
      identify sex differences in incidence, screening uptake, route to diagnosis,
      cancer stage at diagnosis and survival, and their influence in the sex
      differences in mortality. RESULTS: Overall incidence is higher in men, with an
      earlier age distribution, however, important sex differences exist in anatomical
      site. There were relatively small differences in screening uptake, route to
      diagnosis, cancer staging at diagnosis and survival. Screening uptake is higher
      in women under 69 years. Women are more likely to present as emergency cases,
      with more men diagnosed through screening and two-week-wait. No sex differences
      are seen in diagnosis for more advanced disease. Overall, age-standardised 5-year
      survival is similar between the sexes. CONCLUSIONS: As there are minimal sex
      differences in the data from routes to diagnosis to survival, the higher
      mortality of colorectal cancer in men appears to be a result of exogenous and/or
      endogenous factors pre-diagnosis that lead to higher incidence rates. There are
      however, sex and gender differences that suggest more targeted interventions may
      facilitate prevention and earlier diagnosis in both men and women.

PMID- 30236085
TI  - Obesity and depressive symptoms in mid-life: a population-based cohort study.
AB  - BACKGROUND: Obesity and depression are both highly prevalent public health
      disorders and evidence on their relationship is inconsistent. This study examined
      whether depressive symptoms are associated with current obesity, and further,
      whether obesity in turn is associated with an increased odds of depressive
      symptoms five years later after accounting for potential lifestyle confounders
      and depressive symptoms at baseline. METHODS: Data were obtained from the 1958
      British birth cohort (N = 9217 for cross-sectional and 7340 for prospective
      analysis). Clinical Interview Schedule-Revised and Mental Health Inventory-5 were
      used for screening depressive symptoms at ages 45 and 50 years, respectively.
      General and central obesity were defined using measurements of body mass index
      (BMI) and waist circumference (WC) at 45 years, respectively. RESULTS: There was
      a cross-sectional association between depressive symptoms and obesity:
      participants with >=2 depressive symptoms had 31% (95%CI 11% to 55%) higher odds
      of general and 26% higher odds of central obesity (95%CI 8% to 47%). In
      prospective analyses, both general and central obesity were associated with
      higher odds of depressive symptoms five years later among women but not in men
      (Pinteraction < 0.01). After adjustment for depressive symptoms at baseline,
      sociodemographic and lifestyle factors, women with general obesity had 38% (95%
      CI 7% to 77%) and women with central obesity 34% (95%CI 9% to 65%) higher odds of
      depression compared to others. CONCLUSIONS: Depressive symptoms are associated
      with concurrent obesity and related lifestyle factors among women and men in mid
      life. Our study suggests that obesity in turn affects long-term risk of
      depressive symptoms in women but not in men, independently of concurrent
      associations, providing an important target group for the implementation of
      preventative strategies.

PMID- 30236087
TI  - Application of biodegradable collagen matrix (OlogenTM) implants in
      Dacryocystorhinostomy surgeries, a randomized clinical study.
AB  - BACKGROUND: To introduce and evaluate the application of Ologen implants in
      external Dacryocystorhinostomy (DCR) Surgeries. METHODS: Prospective comparative
      randomized study was carried out on 60 patients coming to ophthalmology
      department, Menoufia University Hospitals. Patients included were suffering from
      primary acquired nasolacrimal duct obstruction with positive regurge test.
      Patients were randomly enrolled into two groups using alternating choice
      technique. Group A included 30 patients who had DCR surgery to treat the
      obstruction with Silicone tubes. Group B included 30 patients had a
      Dacryocystorhinostomy with Silicone tubes and Ologen implants. RESULTS: Success
      rates as regard to relief of symptomatic epiphora were 86.7% in group A and 96.7%
      in group B and time of dye clearance test was 4.5 +/- 0.6 min in group A and 3.9
      +/- 0.4 min in group B with p value 0.353 &0.001 consecutively. Apart from
      immediate mild post operative hemorrhage that was encountered in 2 cases in group
      B and 1 case in group A, there were no significant complications in both groups.
      CONCLUSION: The current study shows that application of Ologen implants in
      external DCR surgeries may improve symptomatic epiphora without exposing the
      patients to more intra-operative or post-operative complications. To the best of
      our knowledge, the current study is the first one to use Ologen implants in
      external DCR surgeries. However, the follow-up period was relatively short and
      the sample size is relatively small and further work is required to verify the
      effect of Ologen in external DCR surgeries. TRIAL REGISTRATION: Current
      Controlled Trials PACTR201711002809215 , and the date of registration is 29
      November 2017. The trial is Retrospectively registered.

PMID- 30236086
TI  - Effectiveness of binocularity-stimulating treatment in children with residual
      amblyopia following occlusion.
AB  - BACKGROUND: To evaluate the effectiveness of binocularity-stimulating treatment
      in children with residual amblyopia following occlusion therapy for more than 6
      months. METHODS: Of patients with amblyopia caused by anisometropia and/or
      strabismus, patients with residual amblyopia following more than 6 months of
      occlusion therapy were included. Subjects underwent one of the following types of
      binocularity-stimulating therapy: Bangerter foil (BF), head-mounted display (HMD)
      game, or BF/HMD combination (BF + HMD). Factors including age, sex, types of
      amblyopia, visual acuity, and duration of treatment were investigated. Baseline
      and final (after at least 2 months of treatment) visual acuity were also
      compared. RESULTS: Twenty-two patients with a mean age of 8.7 +/- 1.3 years were
      included. Seven patients had anisometropic amblyopia, 8 patients had strabismic
      amblyopia, and 7 patients had combined amblyopia. After 4.4 +/- 1.8 months of
      treatment, logarithm of the minimum angle of resolution (logMAR) visual acuity in
      the amblyopic eye improved from 0.22 +/- 0.20 to 0.18 +/- 0.15. Five of 22
      patients (22.7%) gained more than 0.2 logMAR, including 1 of 10 patients (10.0%)
      in the BF group, 2 of 7 patients (28.6%) in the HMD group, and 2 of 5 patients
      (40.0%) in the BF + HMD group. No significant differences in clinical
      characteristics were identified among the three groups. CONCLUSIONS: Binocularity
      stimulating therapy is somewhat beneficial in children with residual amblyopia
      and might be attempted when children no longer benefit from sufficient long-term
      period of occlusion therapy.

PMID- 30236088
TI  - Lower youth steps/day values observed at both high and low population density
      areas: a cross-sectional study in metropolitan Tokyo.
AB  - BACKGROUND: Physical activity among children and adolescents (collectively,
      youth) is important to ensure adult health. Population density is a factor that
      affects physical activity via various environmental factors. However, the
      relationship between population density and physical activity among youth is not
      fully understood, especially in extremely high density area. The aim of this
      study was to examine the relationship between population density and physical
      activity of youth using pedometer-determined step data. METHODS: A total of
      13,688 youth between 6 to 15 years of age were identified from the 2011 Tokyo
      Metropolitan Survey of Physical Fitness, Physical Activity and Lifestyle.
      Participants were divided into five subgroups according to the population density
      of their municipality of residence. The population density's fixed effects on in
      school, out-of-school, and daily total step count adjusted for gender and school
      grade were estimated. RESULTS: The lowest (< 2500 people/km2) and highest (>
      10,000 people/km2) population density subgroups had significantly lower daily
      total step count and out-of-school step count than those of the reference
      population (5000-7500 people/km2). In contrast, in-school step count did not
      significantly differ according to population density. CONCLUSIONS: Both low
      population density and also high population density were related to lower step
      count. Low physical activity in high density areas has not been well documented
      in previous research. Considering population growth in urbanized area globally,
      these results suggest the importance of continued research of physical activity
      determinants in high population density areas.

PMID- 30236089
TI  - Association between ambient air pollutants and preterm birth in Ningbo, China: a
      time-series study.
AB  - BACKGROUND: Exposure to air pollutants has been related to preterm birth, but
      little evidence can be available for PM2.5, O3 and CO in China. This study aimed
      to investigate the short-term effect of exposure to air pollutants on risk
      preterm birth during 2014-2016 in Ningbo, China. METHODS: We conducted a time
      series study to evaluate the associations between daily preterm birth and major
      air pollutants (including PM2.5, PM10, SO2, NO2, O3 and CO) in Ningbo during 2014
      2016. A General Additive Model extend Poisson regression was used to evaluate the
      relationship between preterm birth and air pollution with adjustment for time
      trend, meteorological factors and day of the week (DOW). We also conducted a
      subgroup analysis by season and age. RESULTS: In this study, a total of 37,389
      birth occurred between 2014 and 2016 from the Electronic Medical Records System
      of Ningbo Women and Children's Hospital, of which 5428 were verified as preterm
      birth. The single pollutant model suggested that lag effect of PM2.5, PM10, NO2
      reached a peak at day 3 before delivery and day 6 for SO2, and no relationships
      were observed for O3 and preterm birth. Excess risks (95% confidence intervals)
      for an increase of IQR of air pollutant concentrations were 4.84 (95% CI: 1.77,
      8.00) for PM2.5, 3.56 (95% CI: 0.07, 7.17) for PM10, 3.65 (95% CI: 0.86, 6.51)
      for SO2, 6.49 (95% CI: 1.86, 11.34) for NO2, - 0.90 (95% CI: -4.76, 3.11) for O3,
      and 3.36 (95% CI: 0.50, 6.30) for CO. Sensitivity analyses by exclusion of
      maternal age < 18 or > 35 years did not materially alter our results.
      CONCLUSIONS: This study indicates that short-term exposure to air pollutants
      (including PM2.5, PM10, SO2, NO2) are positively associated with risk of preterm
      birth in Ningbo, China.

PMID- 30236090
TI  - Neonatal tactile stimulation at birth in a low-resource setting.
AB  - BACKGROUND: Stimulation is the most common intervention during neonatal
      resuscitation at birth, but scarce information is available on the actual
      methods, timing and efficacy of this basic step. To evaluate the occurrence,
      patterns and response to tactile stimulation at birth in a low-resource setting.
      METHODS: We reviewed 150 video recordings of neonatal resuscitation at Beira
      Central Hospital (Beira, Mozambique). Timing, method, duration and response to
      tactile stimulation were evaluated. RESULTS: One hundred two out of 150 neonates
      (68.0%) received stimulation, while the remaining 48 (32.0%) received positive
      pressure ventilation and/or chest compressions directly. Overall, 546 stimulation
      episodes (median 4 episodes per subject, IQR 2-7) were performed. Median time to
      the first stimulation episode was 134 s (IQR 53-251); 29 neonates (28.4%)
      received stimulation within the first minute after birth. Multiple techniques of
      stimulation were administered in 66 neonates (64.7%), while recommended
      techniques (rubbing the back or flicking the soles of the feet) only in 9 (8.8%).
      Median duration of stimulation was 17 s (IQR 9-33). Only 9 neonates (8.8%)
      responded to stimulation. CONCLUSIONS: In a low-resource setting, stimulation of
      newly born infants at birth is underperformed. Adherence to international
      guidelines is low, resulting in delayed initiation, inadequate technique,
      prolonged duration and low response to stimulation. Back rubs may provide some
      benefits, but large prospective studies comparing different methods of
      stimulation are required.

PMID- 30236091
TI  - Consensus design for improved thermostability of lipoxygenase from Anabaena sp.
      PCC 7120.
AB  - BACKGROUND: Lipoxygenase (LOX) from Anabaena sp. PCC 7120 (Ana-rLOX) offers
      important applications in the food industry, especially for improving aroma and
      dough rheological properties. However, industrial applications of LOXs have been
      limited by their poor thermostability. Herein, we report a bioinformatics-based
      consensus concept approach for the engineering of thermostable Ana-rLOX. RESULTS:
      A series of mutations (N130D, G260A, S437T, N130D/G260Q, N130D/S437Y) showed
      higher thermostability and activity than the wild-type enzyme. Thus, N130D/G260Q
      exhibited a 6.6-fold increase in half-life and 2.45  degrees C increase in
      unfolding temperature; N130D/S437Y showed a 10  degrees C increase in optimal
      temperature. The secondary structure did not change much that contributed to
      improved thermostability were investigated in detail using circular dichroism.
      Homology modeling suggested that enhanced thermostability and specific activity
      may result from favorable hydrophobic interactions. CONCLUSIONS: A series of
      mutations were achieved, showing higher thermostability and activity than the
      wild-type enzyme by semi-rational mutagenesis with limited structure information.
      Our findings provide important new insights into molecular modifications aimed at
      improving Ana-rLOX thermostability and activity.

PMID- 30236093
TI  - Back to the future, again: greater leadership, collaboration and accountability
      to accelerate progress to end TB.
AB  - A first UN General Assembly high-level meeting on the fight against tuberculosis
      (TB) will take place on September 26, 2018. It offers the opportunity to forge
      new concrete commitments and action needed to finance and deliver universal
      access to care and prevention, to address equity and social determinants of TB,
      and to pursue robust research and innovation. These are all needed to accelerate
      declines in TB mortality, incidence, and social and economic burden of the
      disease. This Commentary looks at leadership precedents in action against TB and
      highlights opportunities for bolder accountability and collaboration, especially
      at the country level, to stimulate action and impact.

PMID- 30236092
TI  - Attitudes and barriers associated with seasonal influenza vaccination uptake
      among public health students; a cross-sectional study.
AB  - BACKGROUND: Although research has explored influenza vaccination uptake among
      medical and college students, there is a dearth of research in understanding
      influenza vaccination uptake and attitudes toward the vaccine among future public
      health practitioners. Undergraduate public health students represent future
      public health practitioners who may be a significant educational resource for
      health information, including the importance of vaccinations. METHODS: This cross
      sectional study utilized survey data from 158 undergraduate public health
      students attending a large public university in Southern California. The survey
      assessed public health students' attitudes and beliefs towards the seasonal
      influenza vaccine and seasonal vaccination rates among this population. RESULTS:
      Over 88% of respondents reported having been encouraged to receive the seasonal
      influenza vaccine, while only 43.0% reported receipt. Of the students who
      reported not receiving the vaccine, 49.4% believed it may give them the flu,
      30.4% believed there may be dangerous side effects, and 28.9% believed they were
      not at risk for contracting the flu. Access to health care practitioners (OR:
      3.947, 95% CI [1.308-11.906]) and social encouragement (OR: 3.139, 95% CI [1.447
      6.811]) were significantly associated with receipt of the seasonal influenza
      vaccine. CONCLUSION: As public health program curriculum includes information
      about seasonal influenza vaccination and 68% of the sample were seniors soon to
      be exiting the program with an undergraduate degree in public health education,
      this low seasonal influenza vaccination rate is disturbing. This study may add to
      the body of data demonstrating how knowledge of the vaccine does not always
      guarantee vaccine uptake. Results of the current study suggest that it may be
      beneficial to provide additional information targeted to public health students,
      aimed at mediating safety concerns and increasing social pressure to assist in
      improving vaccine acceptance and rates in this population. Maximizing seasonal
      influenza vaccination uptake by addressing attitudes, barriers and misperceptions
      may not only improve vaccination rates among public health students, but also in
      communities served by these future public health practitioners.

PMID- 30236094
TI  - Environmental niche unfilling but limited options for range expansion by active
      dispersion in an alien cavity-nesting wasp.
AB  - BACKGROUND: Predicting the patterns of range expansion of alien species is
      central to develop effective strategies for managing potential biological
      invasions. Here, we present a study on the potential distribution of the American
      cavity-nesting, Orthoptera-hunting and solitary wasp, Isodontia mexicana
      (Hymenoptera: Sphecidae), which was first detected as alien species in France in
      1960 and now is present in many European countries. After having updated its
      current distribution, we estimated the environmental space (based on bioclimatic
      data and altitude) occupied by the species and subsequently predicted its
      environmental potential distribution under both present and future climatic
      conditions at global scale. RESULTS: The wasp lives in low-altitude areas of the
      Northern hemisphere with moderate temperatures and precipitation. The
      environmental space occupied in the invaded area is practically just a subset
      (42%) of that occupied in the native area, showing a process of environmental
      niche unfilling (i.e. the species only partially fills its environmental niche in
      the invaded range). Besides, I. mexicana could also live in other temperate
      areas, mainly in the Southern hemisphere, particularly close to the coasts.
      However, geographic (oceans) and/or climatic (tropical areas, mountain chains)
      barriers would prevent the species to reach these potential areas unless through
      human trade activity. The species could thus only reach, by active dispersion,
      the remaining invadable areas of Europe. Estimations for the future (2050 and
      2070) predict an expansion through active dispersion towards North in the native
      range and towards North and East in the invaded range, but future conditions
      would not break down the current climatic barriers in the Southern hemisphere.
      CONCLUSIONS: Isodontia mexicana has not shifted its environmental niche in the
      invaded area. It could still occupy some new areas by active dispersion, but
      confined to Europe. The conspicuous niche unfilling shown by this wasp species
      could reflect the likely single introduction in Europe just a few decades ago.
      Furthermore, results stay in line with other studies that found niche unfilling
      rather than niche expansion in insects.

PMID- 30236096
TI  - Lack of advantages of slit mesh placement during laparoscopic transabdominal
      preperitoneal inguinal hernia repair (TAPP): a single centre, case matched study.
AB  - BACKGROUND: During laparoscopic trans-abdominal pre-peritoneal hernia repair
      (TAPP) the positioning of the mesh around the spermatic cord could provide an
      additional anchoring point and ensure better defect closure, thereby preventing
      mesh movement and recurrence. The primary aim of our retrospective study was to
      determine if, during a TAPP procedure, an advantageous difference for mesh
      placement exists between the slit and the non-slit techniques in terms of
      recurrence rate. Secondary aims were intra and post-operative complications and
      the time required to return to normal activity. METHODS: From January 2010 to
      December 2015, data from patients who had undergone TAPPs at our Institution were
      prospectively collected. We performed a retrospective case control matched study
      of two homogenous (BMI, Age, type of hernia) groups of 100 patients who underwent
      respectively TAPP with no slit mesh placement (Group NS) and slit mesh placement
      (Group S). Statistical analysis was carried out using a SPSS 20. To compare
      continuous variables, an independent sample T-test was performed. A Chi-square
      test was employed for categorical data. RESULTS: No differences were found
      between the slit and non-slit groups in terms of biometric features and intra and
      post-operative outcomes were found to be similar in both groups as well. In
      particular, at mean follow-up of 57.34 +/- 10.56 months for Group NS and 55.66 +/
      8.61 months for Group S months only one recurrence per group was found.
      CONCLUSION: Our study failed to prove a superiority of the slit mesh technique
      over the no-slit mesh technique during TAPP. However, in light of its not being a
      randomized study, a subsequent, well-designed RCT would be desirable in order to
      better determine if the Slit mesh technique could prove to be advantageous enough
      to justify its routine use during the TAPP procedure.

PMID- 30236097
TI  - Avoid reinventing the wheel: implementation of the Ottawa Clinic Assessment Tool
      (OCAT) in Internal Medicine.
AB  - BACKGROUND: Workplace based assessment (WBA) is crucial to competency-based
      education. The majority of healthcare is delivered in the ambulatory setting
      making the ability to run an entire clinic a crucial core competency for Internal
      Medicine (IM) trainees. Current WBA tools used in IM do not allow a thorough
      assessment of this skill. Further, most tools are not aligned with the way
      clinical assessors conceptualize performances. To address this, many tools
      aligned with entrustment decisions have recently been published. The Ottawa
      Clinic Assessment Tool (OCAT) is an entrustment-aligned tool that allows for such
      an assessment but was developed in the surgical setting and it is not known if it
      can perform well in an entirely different context. The aim of this study was to
      implement the OCAT in an IM program and collect psychometric data in this
      different setting. Using one tool across multiple contexts may reduce the need
      for tool development and ensure that tools used have proper psychometric data to
      support them. METHODS: Psychometrics characteristics were determined. Descriptive
      statistics and effect sizes were calculated. Scores were compared between levels
      of training (juniors (PGY1), seniors (PGY2s and PGY3s) & fellows (PGY4s and
      PGY5s)) using a one-way ANOVA. Safety for independent practice was analyzed with
      a dichotomous score. Variance components were generated and used to estimate the
      reliability of the OCAT. RESULTS: Three hundred ninety OCATs were completed over
      52 weeks by 86 physicians assessing 44 residents. The range of ratings varied
      from 2 (I had to talk them through) to 5 (I did not need to be there) for most
      items. Mean scores differed significantly by training level (p < .001) with
      juniors having lower ratings (M = 3.80 (out of 5), SD = 0.49) than seniors (M =
      4.22, SD = - 0.47) who had lower ratings than fellows (4.70, SD = 0.36). Trainees
      deemed safe to run the clinic independently had significantly higher mean scores
      than those deemed not safe (p < .001). The generalizability coefficient that
      corresponds to internal consistency is 0.92. CONCLUSIONS: This study's
      psychometric data demonstrates that we can reliably use the OCAT in IM. We
      support assessing existing tools within different contexts rather than continuous
      developing discipline-specific instruments.

PMID- 30236095
TI  - Proteinase 3; a potential target in chronic obstructive pulmonary disease and
      other chronic inflammatory diseases.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a common, multifactorial lung
      disease which results in significant impairment of patients' health and a large
      impact on society and health care burden. It is believed to be the result of
      prolonged, destructive neutrophilic inflammation which results in progressive
      damage to lung structures. During this process, large quantities of neutrophil
      serine proteinases (NSPs) are released which initiate the damage and contribute
      towards driving a persistent inflammatory state.Neutrophil elastase has long been
      considered the key NSP involved in the pathophysiology of COPD. However, in
      recent years, a significant role for Proteinase 3 (PR3) in disease development
      has emerged, both in COPD and other chronic inflammatory conditions. Therefore,
      there is a need to investigate the importance of PR3 in disease development and
      hence its potential as a therapeutic target. Research into PR3 has largely been
      confined to its role as an autoantigen, but PR3 is involved in triggering
      inflammatory pathways, disrupting cellular signalling, degrading key structural
      proteins, and pathogen response.This review summarises what is presently known
      about PR3, explores its involvement particularly in the development of COPD, and
      indicates areas requiring further investigation.

PMID- 30236098
TI  - Availability of post-hospital services supporting community reintegration for
      children with identified surgical need in Uganda.
AB  - BACKGROUND: Community services and supports are essential for children
      transitioning home to recover from the hospital after surgery. This study
      assessed the availability and geographic capacity of rehabilitation, assistive
      devices, familial support, and school reintegration programs for school-aged
      children in Uganda with identified surgical need. METHODS: This study assessed
      the geographic epidemiology and spatial analysis of resource availability in
      communities in Uganda. Participants were children with identified surgical need
      using the Surgeons OverSeas Assessment of Surgical need (SOSAS). Community-based
      resources available to children and adolescents after surgery in Uganda were
      identified using publicly available data sources and searching for resources
      through consultation with in-country collaborators We sought resources available
      in all geographic regions for a variety of services. RESULTS: Of 1082 individuals
      surveyed aged 5 to 14 yearsr, 6.2% had identified surgical needs. Pediatric
      surgical conditions were most prevalent in the Northern and Central regions of
      Uganda. Of the 151 community-based services identified, availability was greatest
      in the Central region and least in the Northern region, regardless of type.
      Assuming 30% of children with surgical needs will need services, a maximum of
      50.1% of these children would have access to the needed services in the extensive
      capacity estimates, while only 10.0% would have access in the minimal capacity
      estimates. The capacity varied dramatically by region with the Northern region
      having much lower capacity in all scenarios as compared to the Central, Eastern,
      or Western regions. CONCLUSIONS: Our study found that beyond the city of Kampala
      in the Central region, community-based services were severely lacking for school
      aged children in Uganda. Increased pediatric surgical capacity to additional
      hospitals in Uganda will need to be met with increased availability and access to
      community-based services to support recovery and community re-integration.

PMID- 30236099
TI  - Direct resin composite restoration of maxillary central incisors using a 3D
      printed template: two clinical cases.
AB  - BACKGROUND: Three-dimensional (3D) printing technology is used widely in
      dentistry for applications including implant surgery, oral and maxillofacial
      surgery, orthognathic surgery, endodontics and prosthodontics. Using a 3D-printed
      template makes performing the repair procedure faster and more convenient. The
      aesthetic restoration of anterior teeth can recover facial beauty, enhance
      speaking and chewing functions and improve the quality of life of the patient.
      CASE PRESENTATION: This article describes two kinds of clinical cases including
      fractured teeth and dental caries. In both, a 3D-printed template was used for
      direct resin composite restoration of maxillary central incisors. A 3D-printed
      template was built using the following 3-step process: data acquisition was
      conducted via intra-oral scanning, virtual modeling was performed using an
      imaging process, and manufacturing was performed using a 3D printer.
      Aesthetically restoring the maxillary incisors with the assistance of the 3D
      printed template achieved the anticipated results, and the patients were very
      satisfied with the effect. CONCLUSIONS: The direct resin composite restoration of
      maxillary central incisors using a 3D-printed template represents a rapid,
      convenient, aesthetic and functional option for treating maxillary central
      incisors. A 3D-printed template is therefore an acceptable and reliable
      alternative to traditional direct composite restoration of maxillary central
      incisors including fractured teeth and dental caries.

PMID- 30236100
TI  - Flow mediated vasodilation compared with carotid intima media thickness in the
      evaluation of early cardiovascular damage in menopausal women and the influence
      of biological and psychosocial factors.
AB  - BACKGROUND: Women after menopause increase risk for cardiovascular disease and
      several factors may be related. The purpose was to study biological and
      psychosocial factors associated with early cardiovascular damage in pre- and
      postmenopausal women, assessed with carotid intima-media thickness vs flow
      mediated dilatation. METHODS: Women 45 to 57 years old were grouped in the pre-
      (n = 60), early (n = 58) and late post-menopause (n = 59). Anthropometric,
      metabolic and hormonal data were registered, as well as measures of depression,
      anxiety, submission, perceived stress, and sleep alterations. Heart Rate
      Variability was recorded to obtain the information regarding sympathovagal
      balance. Carotid intima-media thickness and flow-mediated dilatation were
      assessed by ultrasound. Two-way ANOVA and multiple regression model were used.
      RESULTS: At late postmenopause, the carotid intima-media was thicker (p < 0.001)
      and flow-mediated dilatation decreased (p < 0.001). Carotid intima-media
      thickness was associated positively with age (p < 0.001), submission score (p =
      0.029), follicle stimulating hormone levels (p < 0.001), and body mass index (p =
      0.009). Flow-mediated dilatation was associated only with age (p < 0.001).
      Regarding heart rate variability, the time domain pNN50 measurement was higher in
      premenopausal women (p = 0.001), Low Frequency (LF) was higher in the two groups
      of postmenopausal (p = 0.001) and High Frequency (HF) higher in the early
      postmenopausal women (p = 0.042). CONCLUSIONS: Under our conditions carotid
      intima-media thickness had higher predictive value for early cardiovascular
      damage at menopause. The finding of the association of the submission score,
      indicates de influence of stress on vascular damage.

PMID- 30236101
TI  - Point of care ultrasound training for internal medicine: a Canadian multi-centre
      learner needs assessment study.
AB  - BACKGROUND: Significant gaps currently exist in the Canadian internal medicine
      point-of-care ultrasound (POCUS) curriculum. From a learner's perspective, it
      remains unknown what key POCUS skills should be prioritized. This needs
      assessment study seeks to establish educational priorities for POCUS for internal
      medicine residents at five Canadian residency training programs. METHODS: All
      internal medicine trainees [postgraduate year (PGY) 1-5] from five internal
      medicine residency training programs in Canada (n = 598) were invited to complete
      an online survey on 15 diagnostic POCUS applications, 9 bedside procedures, and
      18 POCUS knowledge items. For POCUS applications and procedures, participants
      were asked how applicable they are to patient care in internal medicine and the
      participants' reported skills in those domains. Self-reported knowledge and
      skills were rated on a 5-point Likert scale, where 1 = very poor and 5 = very
      good. Applicability was rated, where 1 = not at all applicable and 5 = very
      applicable. RESULTS: A total of 253 of 598 residents (42%) participated in our
      study. Data from one centre (n = 15) was removed because of low response rate
      (15%) and significant baseline differences between those trainees and the
      remaining participants. Of the remaining analyzable data from four training
      programs (n = 238), participants reported highest applicability to internal
      medicine for the following applications and procedures: identifying ascites/free
      fluid [mean applicability score of 4.9 +/- standard deviation (SD) 0.4]; gross
      left ventricular function (mean 4.8 +/- SD 0.5) and pericardial effusion (mean
      4.7 +/- SD 0.5); thoracentesis (mean score 4.9 +/- SD 0.3), central line
      insertion (mean 4.9 +/- SD 0.3), and paracentesis (mean 4.9 +/- SD 0.3),
      respectively. Overall reported knowledge/skills was low, with skill gaps being
      the highest for identifying deep vein thrombosis (mean gap 2.7 +/- SD 1.1), right
      ventricular strain (mean 2.7 +/- SD 1.1), and gross left ventricular function
      (mean 2.7 +/- SD 1.0). CONCLUSIONS: Many POCUS applications and procedures were
      felt to be applicable to the practice of internal medicine. Significant skill
      gaps exist in the four Canadian training programs included in the study. POCUS
      curriculum development efforts should target training based on these perceived
      skill gaps.

PMID- 30236102
TI  - Associations between post-operative rehabilitation of hip fracture and outcomes:
      national database analysis.
AB  - BACKGROUND: Rehabilitation programmes are used to improve hip fracture outcomes.
      There is little published trial clinical trial or population-based data on the
      effects of the type or provider of rehabilitation treatments on hip fracture
      outcomes. We evaluated the associations of rehabilitation interventions with post
      operative hip fracture outcomes. METHODS: Cross-sectional (2013-2015) analysis of
      data from the English National Hip Fracture Database (NHFD) from all 191 English
      hospitals treating hip fractures. Of 62,844 NHFD patients, we included 17,708
      patients with rehabilitation treatment and 30-day mobility data, and 34,142
      patients with rehabilitation treatment and discharge destination data. The
      intervention was early mobilisation rehabilitation treatments delivered by a
      physiotherapist (PT, physical therapist in North America) or other clinical staff
      as identifiable in NHFD. We used ordinal logistic and propensity scoring
      regression models to adjust for confounding variables including age, sex, pre
      fracture mobility, operative delay, and cognitive function and peri-operative
      risk scores. RESULTS: In both the adjusted multivariate and propensity-weighted
      analyses, mobilisation on the day or the day following surgery is associated with
      better mobility function 30 days after discharge. However patients mobilised by a
      PT did not have better mobility compared to mobilisation by other professionals.
      Patients who received a PT assessment were not protected from poorer mobility 30
      days after discharge, compared with those who did not receive an assessment. The
      discharge destination outcome is also better in mobilised than unmobilised
      patients, whether done by a PT or another health professional, and the difference
      persists, slightly attenuated, after propensity weighting. CONCLUSIONS: In
      addition to the type of health professional initiating mobilisation, data on
      rehabilitation treatment activity and post-operative gait speed is needed to
      determine optimum rehabilitation dosage and functional outcome. After adjustment
      patients mobilised by non-PTs did as well as patients mobilised by PTs,
      suggesting that PTs' current roles in very early rehabilitation should be
      reconsidered, with a view to redeploying them to more specialised later
      rehabilitation activity.

PMID- 30236103
TI  - Frailty trajectories to identify end of life: a longitudinal population-based
      study.
AB  - BACKGROUND: Timely recognition of the end of life allows patients to discuss
      preferences and make advance plans, and clinicians to introduce appropriate care.
      We examined changes in frailty over 1 year, with the aim of identifying
      trajectories that could indicate where an individual is at increased risk of all
      cause mortality and may require palliative care. METHODS: Electronic health
      records from 13,149 adults (cases) age 75 and over who died during a 1-year
      period (1 January 2015 to 1 January 2016) were age, sex and general practice
      matched to 13,149 individuals with no record of death over the same period
      (controls). Monthly frailty scores were obtained for 1 year prior to death for
      cases, and from 1 January 2015 to 1 January 2016 for controls using the
      electronic frailty index (eFI; a cumulative deficit measure of frailty, available
      in most English primary care electronic health records, and ranging in value from
      0 to 1). Latent growth mixture models were used to investigate longitudinal
      patterns of change and associated impact on mortality. Cases were reweighted to
      the population level for tests of diagnostic accuracy. RESULTS: Three distinct
      frailty trajectories were identified. Rapidly rising frailty (initial increase of
      0.022 eFI per month before slowing from a baseline eFI of 0.21) was associated
      with a 180% increase in mortality (OR 2.84, 95% CI 2.34-3.45) for 2.2% of the
      sample. Moderately increasing frailty (eFI increase of 0.007 per month, with
      baseline of 0.26) was associated with a 65% increase in mortality (OR 1.65, 95%
      CI 1.54-1.76) for 21.2% of the sample. The largest (76.6%) class was stable
      frailty (eFI increase of 0.001 from a baseline of 0.26). When cases were
      reweighted to population level, rapidly rising frailty had 99.1% specificity and
      3.2% sensitivity (positive predictive value 19.8%, negative predictive value
      93.3%) for predicting individual risk of mortality. CONCLUSIONS: People aged over
      75 with frailty who are at highest risk of death have a distinctive frailty
      trajectory in the last 12 months of life, with a rapid initial rise from a low
      baseline, followed by a plateau. Routine measurement of frailty can be useful to
      support clinicians to identify people with frailty who are potential candidates
      for palliative care, and allow time for intervention.

PMID- 30236105
TI  - Examining the impact of accreditation on a primary healthcare organization in
      Qatar.
AB  - BACKGROUND: Although a modest body of literature exists on accreditation, little
      research was conducted on the impact of accreditation on primary healthcare
      organizations in the Middle East. This study assessed the changes resulting from
      the integration of Accreditation Canada International's accreditation program in
      a primary healthcare organization in the State of Qatar. METHODS: The study
      investigated how accreditation helped introduce organizational changes through
      promoting organizational learning as well as quality improvement initiatives.
      Applying a quantitative design, a structured questionnaire was used to collect
      data from 500 staff. The study used Spearman's correlation coefficient to analyze
      the collected survey data. RESULTS: Overall employees agreed on the positive
      impact of accreditation. The results showed a significantly positive correlation
      between staff perception of accreditation and of quality of care. The two
      dominant cultures at Primary Health Care Corporation were "group" (with a score
      of 28.61) and "hierarchical" (with a score of 26.59). The results showed a
      positive correlation between staff perception of accreditation and their
      perception of culture type whenever the culture was identified as "group".
      CONCLUSIONS: This study provided much-needed insight on the possible changes that
      organizations might go through in relation to quality improvement and
      organizational learning.

PMID- 30236104
TI  - Short and long-term effects of pulmonary rehabilitation in interstitial lung
      diseases: a randomised controlled trial.
AB  - BACKGROUND: Few data are available on the long-term effect of pulmonary
      rehabilitation (PR) and on long PR programs in interstitial lung diseases (ILD).
      We aimed to evaluate the effects of PR on exercise capacity (6-Minute Walking
      Distance, 6MWD; Peak Work Rate, Wmax), quality of life (St George's Respiratory
      Questionnaire, SGRQ), quadriceps force (QF) and objectively measured physical
      activity in ILD after the 6-month PR-program and after 1 year. METHODS: 60
      patients (64 +/- 11 years; 62% males; 23% with IPF) were randomly assigned to
      receive a 6 month-PR program or usual medical care. RESULTS: Exercise capacity,
      quality of life and muscle force increased significantly after the program as
      compared to control (mean,95%CI[ll to ul]; 6MWD + 72,[36 to 108] m; Wmax 19, [8
      to 29]%pred; SGRQ - 12,[- 19 to - 6] points; QF 10, [1 to 18] %pred). The gain
      was sustained after 1 year (6MWD 73,[28 to 118] m; Wmax 23, [10 to 35]%pred; SGRQ
      - 11,[- 18 to - 4] points; QF 9.5, [1 to 18] %pred). Physical activity did not
      change. CONCLUSIONS: PR improves exercise tolerance, health status and muscle
      force in ILD. The benefits are maintained at 1-year follow-up. The intervention
      did not change physical activity. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT00882817 .

PMID- 30236106
TI  - Progression-specific genes identified in microdissected formalin-fixed and
      paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive
      ductal breast cancers.
AB  - BACKGROUND: The transition from ductal carcinoma in situ (DCIS) to invasive
      breast carcinoma (IBC) is an important step during breast carcinogenesis.
      Understanding its molecular changes may help to identify high-risk DCIS that
      progress to IBC. Here, we describe a transcriptomic profiling analysis of matched
      formalin-fixed and paraffin-embedded (FFPE) DCIS and IBC components of individual
      breast tumours, containing both tumour compartments. The study was performed to
      validate progression-associated transcripts detected in an earlier gene profiling
      project using fresh frozen breast cancer tissue. In addition, FFPE tissues from
      patients with pure DCIS (pDCIS) were analysed to identify candidate transcripts
      characterizing DCIS with a high or low risk of progressing to IBC. METHODS:
      Fifteen laser microdissected pairs of DCIS and IBC were profiled by Illumina DASL
      technology and used for expression validation by qPCR. Differential expression
      was independently validated using further 25 laser microdissected DCIS/IBC sample
      pairs. Additionally, laser microdissected epithelial cells from 31 pDCIS were
      investigated for expression of candidate transcripts using qPCR. RESULTS:
      Multiple statistical calculation methods revealed 1784 mRNAs which are
      differentially expressed between DCIS and IBC (P < 0.05), of which 124 have also
      been identified in the gene profiling project using fresh frozen breast cancer
      tissue. Nine mRNAs that had been selected from the gene list obtained using fresh
      frozen tissues by applying pathway and network analysis (MMP11, GREM1, PLEKHC1,
      SULF1, THBS2, CSPG2, COL10A1, COL11A1, KRT14) were investigated in tissues from
      the same 15 microdissected specimens and the 25 independent tissue samples by
      qPCR. All selected transcripts were also detected in tumour cells from pDCIS.
      Expression of MMP11 and COL10A1 increased significantly from pDCIS to DCIS of
      DCIS/IBC mixed tumours. CONCLUSION: We confirm differential expression of
      progression-associated transcripts in FFPE breast cancer samples which might
      mediate the transition from DCIS to IBC. MMP11 and COL10A1 may characterize pure
      DCIS with a high risk developing IDC.

PMID- 30236108
TI  - HIV prevention: mapping Mozambican people's views on the acceptability of the
      widow's sexual cleansing ritual called pita-kufa.
AB  - BACKGROUND: In Mozambique, the widow is traditionally required to undergo a
      cleansing ritual called pita-kufa, which generally involves several sessions of
      unprotected sexual intercourse with the brother of her deceased husband. This
      ritual may play a role in the spread of HIV and reveals, to some degree, the
      subordinate position to which women are subjected in Mozambican society. Thus,
      this study's aim was to map Mozambicans' views on the acceptability of this
      ritual, given the gender and public health concerns linked to it. METHODS: A
      total of 359 Mozambicans participated in the study. The data collection
      instrument consisted of 18 vignettes describing realistic pita-kufa situations,
      varying as a function of three factors: a widow's willingness or not to perform
      the ritual, the perceived effectiveness of the ritual, and the risk level of HIV
      infection linked to the practice. For each pita-kufa situation presented in the
      vignettes, the participants were asked to rate its acceptability on an 11-point
      scale. In addition, the participants wrote comments giving their general views on
      the ritual. A cluster analysis using the K-means procedure was applied to the
      quantitative raw data to capture different perspectives, and the participants'
      written comments were subjected to thematic and frequency content analysis.
      RESULTS: From the data gathered though the vignettes, three different
      perspectives were found: total unacceptability (55% of the participants),
      conditional acceptability (29% of the participants) and unconditional
      acceptability (16% of the participants). From the data gathered though the
      participants' written comments, it emerged that they thought that the practice of
      this ritual should evolve (61%), stop (27%) and be kept as it is (12%).
      CONCLUSION: According to the main results, it seems that a large majority of
      study participants think that this ritual is outdated and needs to evolve in
      order to minimize the risk of HIV transmission and respect women's rights.

PMID- 30236107
TI  - Custom made inclusion bodies: impact of classical process parameters and
      physiological parameters on inclusion body quality attributes.
AB  - BACKGROUND: The bacterium E. coli is a major host for recombinant protein
      production of non-glycosylated products. Depending on the expression strategy,
      the recombinant protein can be located intracellularly. In many cases the
      formation of inclusion bodies (IBs), protein aggregates inside of the cytoplasm
      of the cell, is favored in order to achieve high productivities and to cope with
      toxic products. However, subsequent downstream processing, including
      homogenization of the cells, centrifugation or solubilization of the IBs, is
      prone to variable process performance or can be characterized by low extraction
      yields as published elsewhere. It is hypothesized that variations in IB quality
      attributes (QA) are responsible for those effects and that such attributes can be
      controlled by upstream process conditions. This contribution is aimed at
      analyzing how standard process parameters, such as pH and temperature (T) as well
      as different controlled levels of physiological parameters, such as specific
      substrate uptake rates, can vary IB quality attributes. RESULTS: Classical
      process parameters like pH and T influence the expression of analyzed IB. The
      effect on the three QAs titer, size and purity could be successfully revealed.
      The developed data driven model showed that low temperatures and low pH are
      favorable for the expression of the two tested industrially relevant proteins.
      Based on this knowledge, physiological control using specific substrate feeding
      rate (of glucose) qs,Glu is altered and the impact is tested for one protein.
      CONCLUSIONS: Time dependent monitoring of IB QA-titer, purity, IB bead size
      showed a dependence on classical process parameters pH and temperature. These
      findings are confirmed using a second industrially relevant strain. Optimized
      process conditions for pH and temperature were used to determine dependence on
      the physiological parameters, the specific substrate uptake rate (qs,Glu). Higher
      qs,Glu were shown to have a strong influence on the analyzed IB QAs and
      drastically increase the titer and purity in early time stages. We therefore
      present a novel approach to modulate-time dependently-quality attributes in
      upstream processing to enable robust downstream processing.

PMID- 30236109
TI  - Reduced PRC2 function alters male germline epigenetic programming and paternal
      inheritance.
AB  - BACKGROUND: Defining the mechanisms that establish and regulate the transmission
      of epigenetic information from parent to offspring is critical for understanding
      disease heredity. Currently, the molecular pathways that regulate epigenetic
      information in the germline and its transmission to offspring are poorly
      understood. RESULTS: Here we provide evidence that Polycomb Repressive Complex 2
      (PRC2) regulates paternal inheritance. Reduced PRC2 function in mice resulted in
      male sub-fertility and altered epigenetic and transcriptional control of
      retrotransposed elements in foetal male germ cells. Males with reduced PRC2
      function produced offspring that over-expressed retrotransposed pseudogenes and
      had altered preimplantation embryo cleavage rates and cell cycle control.
      CONCLUSION: This study reveals a novel role for the histone-modifying complex,
      PRC2, in paternal intergenerational transmission of epigenetic effects on
      offspring, with important implications for understanding disease inheritance.

PMID- 30236110
TI  - Inhaled furosemide for relief of air hunger versus sense of breathing effort: a
      randomized controlled trial.
AB  - BACKGROUND: Inhaled furosemide offers a potentially novel treatment for dyspnoea,
      which may reflect modulation of pulmonary stretch receptor feedback to the brain.
      Specificity of relief is unclear because different neural pathways may account
      for different components of clinical dyspnoea. Our objective was to evaluate if
      inhaled furosemide relieves the air hunger component (uncomfortable urge to
      breathe) but not the sense of breathing work/effort of dyspnoea. METHODS: A
      randomised, double blind, placebo-controlled crossover trial in 16 healthy
      volunteers studied in a university research laboratory. Each participant received
      3 mist inhalations (either 40 mg furosemide or 4 ml saline) separated by 30-60
      min on 2 test days. Each participant was randomised to mist order 'furosemide
      saline-furosemide' (n- = 8) or 'saline-furosemide-saline' (n = 8) on both days.
      One day involved hypercapnic air hunger tests (mean +/- SD PCO2 = 50 +/- 3.7
      mmHg; constrained ventilation = 9 +/- 1.5 L/min), the other involved work/effort
      tests with targeted ventilation (17 +/- 3.1 L/min) and external resistive load
      (20cmH2O/L/s). Primary outcome was ratings of air hunger or work/effort every 15
      s on a visual analogue scale. During saline inhalations, 1.5 mg furosemide was
      infused intravenously to match the expected systemic absorption from the lungs
      when furosemide is inhaled. Corresponding infusions of saline during furosemide
      inhalations maintained procedural blinding. Average visual analogue scale ratings
      (%full scale) during the last minute of air hunger or work/effort stimuli were
      analysed using Linear Mixed Methods. RESULTS: Data from all 16 participants were
      analysed. Inhaled furosemide relative to inhaled saline significantly improved
      visual analogues scale ratings of air hunger (Least Squares Mean +/- SE - 9.7 +/-
      2%; p = 0.0015) but not work/effort (+ 1.6 +/- 2%; p = 0.903). There were no
      significant adverse events. CONCLUSIONS: Inhaled furosemide was effective at
      relieving laboratory induced air hunger but not work/effort in healthy adults;
      this is consistent with the notion that modulation of pulmonary stretch receptor
      feedback by inhaled furosemide leads to dyspnoea relief that is specific to air
      hunger, the most unpleasant quality of dyspnoea. FUNDING: Oxford Brookes
      University Central Research Fund. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT02881866 . Retrospectively registered on 29th August 2018.

PMID- 30236111
TI  - The future disposition Inventory-24: reliability and validity estimates in a
      large sample of Chinese University students.
AB  - BACKGROUND: This study was designed to assess the factor structure, internal
      consistency reliability, and preliminary psychometric properties of the Chinese
      version of the Future Disposition Inventory-24 (FDI-24) in a large sample of
      Chinese university students. METHODS: We translated the English version of the
      Future Disposition Inventory-24 (FDI-24) into Chinese and examined its factor
      structure, estimates of internal consistency reliability, and psychometric
      properties in a representative sample of university students. In particular,
      students (N = 2,074) from two universities in Shandong Province in China were
      identified using the multi-stage stratified sampling method. In addition to the
      FDI-24, we collected preliminary data using self-report instruments that included
      the Beck Hopelessness Scale (BHS) and a general sociodemographic information
      questionnaire. RESULTS: The results of the internal consistency reliability
      estimates were adequate regarding the scores on the three FDI-24 subscales:
      Cronbach's alpha = .89-.97, Omega total = .85-.96, Revelle's Omega total = .88
      .96, the greatest lower bound (GLB) = .89-.96 and Coefficient H = .86-.94.
      Bivariate correlation analyses showed evidence for criterion and discriminant
      validity. The 3-factor oblique-Geomin-rotation solution accounted for 62.92% of
      the total variance in the exploratory factor analysis (EFA). The exploratory
      structural equation modeling (ESEM) result showed that the 3-factor model
      provided adequate fit statistics for the sample data: the robust comparative fit
      index (R-CFI) was .959, robust Tucker Lewis index (R-TLI) was .946 and robust
      root mean square error of approximation (R-RMSEA) was .090. CONCLUSION: The FDI
      24 has a satisfactory factor structure, reliability estimates, and satisfactory
      evidence of concurrent validity estimates for students with different demographic
      and cultural backgrounds. The FDI-24 holds promise for use in future
      investigations with Chinese students.

PMID- 30236112
TI  - Hypocalcaemia in patients with prostate cancer treated with a bisphosphonate or
      denosumab: prevention supports treatment completion.
AB  - BACKGROUND: Most patients with advanced prostate cancer develop bone metastases,
      which often result in painful and debilitating skeletal-related events.
      Inhibitors of bone resorption, such as bisphosphonates and denosumab, can each
      reduce the incidence of skeletal-related events and delay the progression of bone
      pain. However, these agents are associated with an increased risk of
      hypocalcaemia, which, although often mild and transient, can be serious and life
      threatening. Here we provide practical advice on managing the risk of
      hypocalcaemia in patients with advanced prostate cancer who are receiving
      treatment with bone resorption inhibitors. Relevant references for this review
      were identified through searches of PubMed with the search terms 'prostate
      cancer', 'bone-targeted agents', 'anti-resorptive agents', 'bisphosphonates',
      'zoledronic acid', 'denosumab', 'hypocalcaemia', and 'hypocalcemia'. Additional
      references were suggested by the authors. MAIN TEXT: Among patients with advanced
      cancer receiving a bisphosphonate or denosumab, hypocalcaemia occurs most
      frequently in those with prostate cancer, although it can occur in patients with
      any tumour type. Consistent with its greater ability to inhibit bone resorption,
      denosumab has shown superiority in the prevention of skeletal-related events in
      patients with bone metastases from solid tumours. Consequently, denosumab is more
      likely to induce hypocalcaemia than the bisphosphonates. Likewise, various
      bisphosphonates have differing potencies for the inhibition of bone resorption,
      and thus the risk of hypocalcaemia varies between different bisphosphonates.
      Other risk factors for the development of hypocalcaemia include the presence of
      osteoblastic metastases, vitamin D deficiency, and renal insufficiency.
      Hypocalcaemia can lead to treatment interruption, but it is both preventable and
      manageable. Serum calcium concentrations should be measured, and any pre-existing
      hypocalcaemia should be corrected, before starting treatment with inhibitors of
      bone resorption. Once treatment has started, concomitant administration of
      calcium and vitamin D supplements is essential. Calcium concentrations should be
      monitored during treatment with bisphosphonates or denosumab, particularly in
      patients at high risk of hypocalcaemia. If hypocalcaemia is diagnosed, patients
      should receive treatment with calcium and vitamin D. CONCLUSION: With
      preventative strategies and treatment, patients with prostate cancer who are at
      risk of, or who develop, hypocalcaemia should be able to continue to benefit from
      treatment with bisphosphonates or denosumab.

PMID- 30236113
TI  - Serum phosphate and phosphate-regulatory hormones in COPD patients.
AB  - BACKGROUND: Fibroblast growth factor 23 (FGF23) regulates phosphate metabolism by
      increasing renal phosphate excretion and decreasing 1.25-dihydroxyvitamin D
      synthesis. Reports about hypophosphatemia in patients with chronic obstructive
      pulmonary disease (COPD) suggest altered phosphate metabolism. Therefore, we
      hypothesized that disturbances in phosphate-regulatory hormones such as FGF23 and
      parathyroid hormone (PTH) are present in COPD patients. METHODS: We investigated
      40 COPD patients (63.5 +/- 9.9 years, 27 male), each matched with two age- and
      sex-matched controls without any primary lung disease. COPD patients underwent
      lung function testing in advance. All patients had a glomerular filtration rate
      (GFR) > 60 mL/min/1.73m2. We measured concentrations of intact FGF23 (iFGF23) and
      c-terminal FGF23 (c-term FGF23), phosphate, parathyroid hormone (PTH) and C
      reactive protein (CRP) levels in COPD patients and controls. RESULTS: Phosphate
      (1.0 +/- 02 vs. 1.1 +/- 0.2 mmol/L; p = 0.027), PTH (54.2 +/- 29.4 vs. 68.7 +/-
      31.8 pg/mL; p = 0.002) and iFGF23 (46.3 +/- 29.0 vs. 57.5 +/- 33.5 pg/mL; p =
      0.026 ) levels were significantly lower in COPD patients compared with controls.
      There was a significant negative correlation between c-term FGF23 and total lung
      capacity (r = - 0.4; p = 0.01), and between c-term FGF23 and CRP in COPD patients
      (r = 0.48; p = 0.002). iFGF23 and c-term FGF23 were positively correlated with
      phosphate and PTH in the control group. CONCLUSION: We confirmed lower average
      serum phosphate levels in COPD patients compared with controls. However, our data
      do not suggest a causative role for FGF23 or PTH in COPD because levels of both
      phosphate-lowering hormones appear to be adaptively decreased as well. Therefore,
      further investigations are needed to identify the pathogenesis of low phosphate
      levels in patients with COPD and the relationship between phosphate-regulatory
      hormones and disease progression.

PMID- 30236116
TI  - Correction to: Imported and autochthonous malaria in West Saudi Arabia: results
      from a reference hospital.
AB  - Following publication of the original article [1], it was flagged by one of the
      authors that the name of the P. falciparum gene marker of artemisinin resistance
      'pfkelch13' was (incorrectly) written as "pfketch13", which was repeated seven
      times in different parts of the published paper.

PMID- 30236115
TI  - CircRNA microarray profiling identifies a novel circulating biomarker for
      detection of gastric cancer.
AB  - CircRNA expression profiles for gastric cancer (GC) were screened using plasma
      samples from 10 GC patients with different TNM stages and 5 healthy individuals
      as controls. Results showed lower expression of circ-KIAA1244 in GC tissues,
      plasmas, and cells compare to normal controls. Further clinical data analysis
      demonstrated that a decreased expression of circ-KIAA1244 in plasmas was
      negatively correlated with TNM stage and lymphatic metastasis, and a shorter
      overall survival time of GC patients. Moreover, we found that circ-KIAA1244 could
      be detected in GC plasma exosomes and showed no obvious significance compared to
      the expression level in the corresponding plasmas. This study revealed a GC
      tissues-derived circ-KIAA1244 could serve a novel circulating biomarker for
      detection of GC.

PMID- 30236114
TI  - Biocompatible glyconanomaterials based on HPMA-copolymer for specific targeting
      of galectin-3.
AB  - BACKGROUND: Galectin-3 (Gal-3) is a promising target in cancer therapy with a
      high therapeutic potential due to its abundant localization within the tumor
      tissue and its involvement in tumor development and proliferation. Potential
      clinical application of Gal-3-targeted inhibitors is often complicated by their
      insufficient selectivity or low biocompatibility. Nanomaterials based on N-(2
      hydroxypropyl)methacrylamide (HPMA) nanocarrier are attractive for in vivo
      application due to their good water solubility and lack of toxicity and
      immunogenicity. Their conjugation with tailored carbohydrate ligands can yield
      specific glyconanomaterials applicable for targeting biomedicinally relevant
      lectins like Gal-3. RESULTS: In the present study we describe the synthesis and
      the structure-affinity relationship study of novel Gal-3-targeted
      glyconanomaterials, based on hydrophilic HPMA nanocarriers. HPMA nanocarriers
      decorated with varying amounts of Gal-3 specific epitope GalNAcbeta1,4GlcNAc
      (LacdiNAc) were analyzed in a competitive ELISA-type assay and their binding
      kinetics was described by surface plasmon resonance. We showed the impact of
      various linker types and epitope distribution on the binding affinity to Gal-3.
      The synthesis of specific functionalized LacdiNAc epitopes was accomplished under
      the catalysis by mutant beta-N-acetylhexosaminidases. The glycans were conjugated
      to statistic HPMA copolymer precursors through diverse linkers in a defined
      pattern and density using Cu(I)-catalyzed azide-alkyne cycloaddition. The
      resulting water-soluble and structurally flexible synthetic glyconanomaterials
      exhibited affinity to Gal-3 in low MUM range. CONCLUSIONS: The results of this
      study reveal the relation between the linker structure, glycan distribution and
      the affinity of the glycopolymer nanomaterial to Gal-3. They pave the way to
      specific biomedicinal glyconanomaterials that target Gal-3 as a therapeutic goal
      in cancerogenesis and other disorders.

PMID- 30236117
TI  - Molecular identification of Plasmodium species in symptomatic children of
      Democratic Republic of Congo.
AB  - BACKGROUND: Worldwide, the highest malaria mortality is due to Plasmodium
      falciparum infection. However, other species of Plasmodium (Plasmodium vivax,
      Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi) can also cause
      malaria. Therefore, accurate identification of malaria species is crucial for
      patient management and epidemiological surveillance. This study aimed to
      determine the different Plasmodium species causing malaria in children under 5
      years old in two provinces (Kinshasa and North Kivu) of the Democratic Republic
      of Congo (DRC). METHODS: From October to December 2015, a health-facility based
      cross-sectional study was conducted in General Reference Hospitals in Kinshasa
      and North Kivu. Four hundred and seven blood samples were collected from febrile
      children aged <= 5 years. Nested polymerase chain reaction assays were performed
      for Plasmodium species identification. RESULTS: Out of 407 children, 142 (34.9%)
      were infected with Plasmodium spp. and P. falciparum was the most prevalent
      species (99.2%). Among those infected children, 124 had a mono infection with P.
      falciparum and one with P. malariae. Mixed infections with P. falciparum/P.
      malariae and P. falciparum/P. vivax were observed in 6 (1.5%) and 8 (2.0%)
      children, respectively. The prevalence of infection was higher in females (64.8%)
      than in males (35.2%), p < 0.001. The age-specific distribution of infection
      showed that children of less than 2 years old were less infected (18.4%) compared
      to those aged above 2 years (81.6%), p < 0.001. CONCLUSION: Although this study
      showed clearly that the most prevalent species identified was P. falciparum, the
      findings demonstrate the existence of non-falciparum malaria, especially P.
      malariae and P. vivax among children aged <= 5 years living both Kinshasa and
      North Kivu Provinces in DRC.

PMID- 30236118
TI  - Acceptance of pharmaceutical cannabis substitution by cannabis using patients
      with schizophrenia.
AB  - BACKGROUND: Cannabis-smoking patients with a psychotic disorder have poorer
      disease outcomes than non-cannabis-smoking patients with poorest outcomes in
      patients smoking high-potency cannabis (HPC) containing high Delta9
      tetrahydrocannabinol (THC) and low cannabidiol (CBD). Quitting cannabis smoking
      or substitution of HPC by cannabis variants containing less THC and/or more CBD
      may benefit these patients. The present study explores whether daily HPC-smoking
      patients with schizophrenia accept smoking such variants. METHODS: Twelve male
      patients were asked to smoke on six different occasions one joint: on two
      occasions, the cannabis they routinely smoke (HPC; not blind), and blind in
      random order; on two occasions, cannabis containing low THC and no CBD; and on
      two occasions, cannabis containing low THC and high CBD. RESULTS: Both substitute
      variants were appreciated, but patients preferred the HPC they usually smoked.
      The effect of the low THC/high CBD variant was reported by 32% to be too short
      and by 36% to be not strong enough, whereas this was reported by 5% and 64%,
      respectively, for the low THC cannabis variant. CONCLUSIONS: Based on these
      findings, a larger and longer study on the efficacy of cannabis substitution
      treatment in HPC-smoking patients with schizophrenia seems feasible and should be
      considered. TRIAL REGISTRATION: 2014-005540-17NL . Registered 22 October 2014,
      2014-005540-17NL 20141215 CTA.xml.

PMID- 30236119
TI  - Health-related quality of life impact of minor and major bleeding events during
      dual antiplatelet therapy: a systematic literature review and patient preference
      elicitation study.
AB  - BACKGROUND: Dual antiplatelet therapy (DAPT) is the recommended preventative
      treatment for secondary ischaemic events, but increases the risk of bleeding,
      potentially affecting patients' health-related quality-of-life (HRQoL). Varied
      utility decrements have been used in cost-effectiveness models assessing
      alternative DAPT regimens, but it is unclear which of these decrements are most
      appropriate. Therefore, we reviewed existing sources of utility decrements for
      bleeds in patients receiving DAPT and undertook primary research to estimate
      utility decrements through a patient elicitation exercise using vignettes and the
      EuroQol EQ-5D. METHODS: MEDLINE, PubMed and references of included studies were
      searched. Primary research and decision analytic modelling studies reporting
      utility decrements for bleeds related to DAPT were considered. For the primary
      research study, 21 participants completed an elicitation exercise involving
      vignettes describing minor and major bleeds and the EQ-5D-3 L and EQ-5D-5 L.
      Utility decrements were derived using linear regression and compared to existing
      estimates. RESULTS: Four hundred forty-two citations were screened, of which 12
      studies were included for review. Reported utility decrements ranged from - 0.002
      to - 0.03 for minor bleeds and - 0.007 to - 0.05 for major bleeds. Data sources
      used to estimate the decrements, however, lacked relevance to our population
      group and few studies adequately reported details of their measurement and
      valuation approaches. No study completely adhered to reimbursement agency
      requirements in the UK according to the National Institute for Health and Care
      Excellence reference case. Our primary research elicited utility decrements
      overlapped existing estimates, ranging from - 0.000848 to - 0.00828 for minor
      bleeds and - 0.0187 to - 0.0621 for major bleeds. However, the magnitude of
      difference depended on the instrument, estimation method and valuation approach
      applied. CONCLUSIONS: Several sources of utility decrements for bleeds are
      available for use in cost-effectiveness analyses, but are of limited quality and
      relevance. Our elicitation exercise has derived utility decrements from a
      relevant patient population, based on standardised definitions of minor and major
      bleeding events, using a validated HRQoL instrument and have been valued using
      general population tariffs. We suggest that our utility decrements be used in
      future cost-effectiveness analyses of DAPT.

PMID- 30236120
TI  - Government roles in regulating medical tourism: evidence from Guatemala.
AB  - BACKGROUND: Regulation of the medical tourism and public health sectors overlap
      in many instances, raising questions of how patient safety, economic growth, and
      health equity can be protected. The case of Guatemala is used to explore how the
      regulatory challenges posed by medical tourism should be dealt with in countries
      seeking to grow this sector. METHODS: We conducted a qualitative case study of
      the medical tourism sector in Guatemala, through reviews and analyses of policy
      documents and media reports, key informant interviews (n = 50), and facility site
      visits. RESULTS: Key informants were critical of the absence of effective public
      regulation of the emerging medical tourism sector, noting several regulatory gaps
      and the importance of filling them. These informants specifically expressed that:
      1) The government should regulate medical tourism in Guatemala, thought there was
      disagreement as to which government sector should do so and how; 2) The
      government has not at this time regulated the medical tourism sector nor shown
      great interest in doing so; and 3) International accreditation could be used to
      augment domestic regulation. CONCLUSIONS: The intersection of domestic and
      international regulation of medical tourism has been largely unexplored. This
      case study advances new research in this area. It highlights the need for and
      dearth of regulatory protections in Guatemala and lessons for other, similarly
      situated countries. National regulatory models from Israel and Barbados could be
      adapted to the Guatemalan context. Global governance could help to protect
      national governments from any competitive disadvantages created by regulation.
      Underlying the concerns over growth in medical tourism, however, is how it
      contributes to the ongoing privatization of health care facilities worldwide.
      This trend risks undermining efforts to reach targets for Universal Health
      Coverage and exacerbating existing inequities in the global distribution of
      health and wealth.

PMID- 30236121
TI  - Ablation outcome of irreversible electroporation on potato monitored by impedance
      spectrum under multi-electrode system.
AB  - BACKGROUND: Irreversible electroporation (IRE) therapy relies on pulsed electric
      fields to non-thermally ablate cancerous tissue. Methods for evaluating IRE
      ablation in situ are critical to assessing treatment outcome. Analyzing changes
      in tissue impedance caused by electroporation has been proposed as a method for
      quantifying IRE ablation. In this paper, we assess the hypothesis that
      irreversible electroporation ablation outcome can be monitored using the
      impedance change measured by the electrode pairs not in use, getting more
      information about the ablation size in different directions. METHODS: Using a
      square four-electrode configuration, the two diagonal electrodes were used to
      electroporate potato tissue. Next, the impedance changes, before and after
      treatment, were measured from different electrode pairs and the impedance
      information was extracted by fitting the data to an equivalent circuit model.
      Finally, we correlated the change of impedance from various electrode pairs to
      the ablation geometry through the use of fitted functions; then these functions
      were used to predict the ablation size and compared to the numerical simulation
      results. RESULTS: The change in impedance from the electrodes used to apply
      pulses is larger and has higher deviation than the other electrode pairs. The
      ablation size and the change in resistance in the circuit model correlate with
      various linear functions. The coefficients of determination for the three
      functions are 0.8121, 0.8188 and 0.8691, respectively, showing satisfactory
      agreement. The functions can well predict the ablation size under different pulse
      numbers, and in some directions it did even better than the numerical simulation
      method, which used different electric field thresholds for different pulse
      numbers. CONCLUSIONS: The relative change in tissue impedance measured from the
      non-energized electrodes can be used to assess ablation size during treatment
      with IRE according to linear functions.

PMID- 30236122
TI  - Prostaglandin D2/J2 signaling pathway in a rat model of neuroinflammation
      displaying progressive parkinsonian-like pathology: potential novel therapeutic
      targets.
AB  - BACKGROUND: Prostaglandins are products of the cyclooxygenase pathway, which is
      implicated in Parkinson's disease (PD). Limited knowledge is available on
      mechanisms by which prostaglandins contribute to PD neurodegeneration. To address
      this gap, we focused on the prostaglandin PGD2/J2 signaling pathway, because PGD2
      is the most abundant prostaglandin in the brain, and the one that increases the
      most under pathological conditions. Moreover, PGJ2 is spontaneously derived from
      PGD2. METHODS: In this study, we determined in rats the impact of unilateral
      nigral PGJ2-microinfusions on COX-2, lipocalin-type PGD2 synthase (L-PGDS),
      PGD2/J2 receptor 2 (DP2), and 15 hydroxyprostaglandin dehydrogenase (15-PGDH).
      Nigral dopaminergic (DA) and microglial distribution and expression levels of
      these key factors of the prostaglandin D2/J2 pathway were evaluated by
      immunohistochemistry. PGJ2-induced motor deficits were assessed with the cylinder
      test. We also determined whether oral treatment with ibuprofen improved the PD
      like pathology induced by PGJ2. RESULTS: PGJ2 treatment induced progressive PD
      like pathology in the rats. Concomitant with DA neuronal loss in the substantia
      nigra pars compacta (SNpc), PGJ2-treated rats exhibited microglia and astrocyte
      activation and motor deficits. In DA neurons, COX-2, L-PGDS, and 15-PGDH levels
      increased significantly in PGJ2-treated rats compared to controls, while DP2
      receptor levels were unchanged. In microglia, DP2 receptors were basically non
      detectable, while COX-2 and L-PGDS levels increased upon PGJ2-treatment, and 15
      PGDH remained unchanged. 15-PGDH was also detected in oligodendrocytes. Notably,
      ibuprofen prevented most PGJ2-induced PD-like pathology. CONCLUSIONS: The PGJ2
      induced rat model develops progressive PD pathology, which is a hard-to-mimic
      aspect of this disorder. Moreover, prevention of most PGJ2-induced PD-like
      pathology with ibuprofen suggests a positive feedback mechanism between PGJ2 and
      COX-2 that could lead to chronic neuroinflammation. Notably, this is the first
      study that analyzes the nigral dopaminergic and microglial distribution and
      levels of factors of the PGD2/J2 signaling pathway in rodents. Our findings
      support the notions that upregulation of COX-2 and L-PGDS may be important in the
      PGJ2 evoked PD-like pathology, and that neuronal DP2 receptor antagonists and L
      PGDS inhibitors may be novel pharmacotherapeutics to relieve neuroinflammation
      mediated neurodegeneration in PD, circumventing the adverse side effects of
      cyclooxygenase inhibitors.

PMID- 30236123
TI  - Regional expiratory time constants in severe respiratory failure estimated by
      electrical impedance tomography: a feasibility study.
AB  - BACKGROUND: Electrical impedance tomography (EIT) has been used to guide
      mechanical ventilation in ICU patients with lung collapse. Its use in patients
      with obstructive pulmonary diseases has been rare since obstructions could not be
      monitored on a regional level at the bedside. The current study therefore
      determines breath-by-breath regional expiratory time constants in intubated
      patients with chronic obstructive pulmonary disease (COPD) and acute respiratory
      distress syndrome (ARDS). METHODS: Expiratory time constants calculated from the
      global impedance EIT signal were compared to the pneumatic volume signals
      measured with an electronic pneumotachograph. EIT-derived expiratory time
      constants were additionally determined on a regional and pixelwise level.
      However, regional EIT signals on a single pixel level could in principle not be
      compared with similar pneumatic changes since these measurements cannot be
      obtained in patients. For this study, EIT measurements were conducted in 14
      intubated patients (mean Simplified Acute Physiology Score II (SAPS II) 35 +/-
      10, mean time on invasive mechanical ventilation 36 +/- 26 days) under four
      different positive end-expiratory pressure (PEEP) levels ranging from 10 to 17
      cmH2O. Only patients with moderate-severe ARDS or COPD exacerbation were included
      into the study, preferentally within the first days following intubation.
      RESULTS: Spearman's correlation coefficient for comparison between EIT-derived
      time constants and those from flow/volume curves was between 0.78 for tau (tau)
      calculated from the global impedance signal up to 0.83 for the mean of all
      pixelwise calculated regional impedance changes over the entire PEEP range.
      Furthermore, Bland-Altman analysis revealed a corresponding bias of 0.02 and 0.14
      s within the limits of agreement ranging from - 0.50 to 0.65 s for the
      aforementioned calculation methods. In addition, exemplarily in patients with
      moderate-severe ARDS or COPD exacerbation, different PEEP levels were shown to
      have an influence on the distribution pattern of regional time constants.
      CONCLUSIONS: EIT-based determination of breath-by-breath regional expiratory time
      constants is technically feasible, reliable and valid in invasively ventilated
      patients with severe respiratory failure and provides a promising tool to
      individually adjust mechanical ventilation in response to the patterns of
      regional airflow obstruction. TRIAL REGISTRATION: German Trial Register DRKS
      00011650 , registered 01/31/17.

PMID- 30236124
TI  - Moderate hypothermia inhibits microglial activation after traumatic brain injury
      by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathway.
AB  - BACKGROUND: Complex mechanisms participate in microglial activation after a
      traumatic brain injury (TBI). TBI can induce autophagy and apoptosis in neurons
      and glial cells, and moderate hypothermia plays a protective role in the acute
      phase of TBI. In the present study, we evaluated the effect of TBI and moderate
      hypothermia on microglial activation and investigated the possible roles of
      autophagy/apoptosis and toll-like receptor 4 (TLR4). METHODS: The TBI model was
      induced with a fluid percussion TBI device. Moderate hypothermia was achieved
      under general anesthesia by partial immersion in a water bath for 4 h. All rats
      were killed 24 h after the TBI. RESULTS: Our results showed downregulation of the
      microglial activation and autophagy, but upregulation of microglial apoptosis,
      upon post-TBI hypothermia treatment. The expression of TLR4 and downstream
      myeloid differentiation primary response 88 (MyD88) was attenuated. Moderate
      hypothermia reduced neural cell death post-TBI. CONCLUSIONS: Moderate hypothermia
      can reduce the number of activated microglia by inhibiting autophagy and
      promoting apoptosis, probably through a negative modulation between autophagy and
      apoptosis. Moderate hypothermia may attenuate the pro-inflammatory function of
      microglia by inhibiting the MyD88-dependent TLR4 signaling pathway.

PMID- 30236126
TI  - Hyperoxia effects on intensive care unit mortality: a retrospective pragmatic
      cohort study.

PMID- 30236125
TI  - Independent determinants of prolonged emergency department length of stay in a
      tertiary care centre: a prospective cohort study.
AB  - BACKGROUND: Emergency department (ED) overcrowding is a potential threat for
      patient safety. We searched for independent determinants of prolonged ED length
      of stay (LOS) with the aim to identify factors which can be targeted to reduce ED
      LOS, which may help in preventing overcrowding. METHODS: This prospective cohort
      study included consecutive ED patients in a Dutch tertiary care centre.
      Multivariable logistic regression analysis was used to identify independent
      determinants of ED LOS > 4 h, including patient characteristics (demographics,
      referral type, acuity, (number of) presenting complaints and comorbidity),
      treating specialty, diagnostic testing, consultations, number of patients in the
      ED and disposition. Furthermore, we quantified the absolute time delays (measured
      in real-time) associated with the most important independent determinants of
      prolonged ED LOS. RESULTS: In 1434 included patients independent determinants of
      prolonged ED LOS were number and type of presenting complaints, specialty,
      laboratory/radiology testing and consultations, and ICU admission. Modifiable
      determinants with the largest impact were blood testing; Adjusted odds ratio (AOR
      (95%-CI)); 3.45 (1.95-6.11), urine testing; 1.79 (1.21-2.63), radiology imaging;
      3.02 (2.13-4.30), and consultation; 5.90 (4.08-8.54). Combined with the
      laboratory/radiology testing and/or consultations (requested in 1123 (78%)
      patients) the decision-making and discharge process consumed between 74 (42%) and
      117 (66%) minutes of the total ED LOS of 177 (IQR: 129-225) minutes. CONCLUSIONS:
      In tertiary care EDs, ED LOS can be reduced if the process of
      laboratory/radiology testing and consulting is optimized and the decision-making
      and discharge procedures are accelerated.

PMID- 30236128
TI  - Posterior hemivertebra resection with unilateral instrumented fusion in children
      less than 10 years old: preliminary results at minimum 5-year follow-up.
AB  - BACKGROUND: The main treatment for congenital hemivertebra is posterior
      hemivertebrectomy with bilateral transpedicular fixation. To date, studies
      describing posterior unilateral fusion are few, especially in younger children.
      The modified method by posterior hemivertebrectomy combined with unilateral
      transpedicular instrumentation and fusion was described. The purpose was to
      present the clinical and radiological outcome of children less than 10 years
      treated for congenital scoliosis with posterior hemivertebrectomy and unilateral
      instrumented fusion. METHODS: A study of 43 consecutive patients through Jan.
      2006 to Mar. 2013 for hemivertebrae in children less than 10 years was performed.
      Patients undergoing hemivertebrectomy and posterior convex short-segment fusion,
      which had been followed up for at least 60 months, were included. Coronal main
      curve, kyphosis, T1-S1 height, fused vertebra height, and concave height were
      measured at preoperation, immediate postoperation, and final follow-up. The
      outcome and efficacy of the correction provided and growth of the non-fused
      concave side of the spine was investigated. RESULTS: The average follow-up period
      was 73.88 +/- 16.77 months. The mean Cobb angle of the coronal curve was improved
      from 46.1 to 8.1 degrees  (correction rate 82.4%). At final follow-up, there was
      7.8% loss of correction. The average concave height, fusion segment height, and
      T1-S1 height were 60.1 +/- 19.7 mm, 56.9 +/- 22.9 mm, and 326.6 +/- 64.5 mm in
      immediate postoperation, which improved to 73.1 +/- 23.7 mm, 71.2 +/- 22.0 mm,
      and 388.7 +/- 78.9 mm at the last follow-up. These parameters were significantly
      different between the immediate postoperation and at final follow-up. The rate of
      reoperation was 9.3% (4/43), mainly in PJK and curve progression after surgery.
      CONCLUSIONS: Despite with some complications, posterior hemivertebrectomy and
      unilateral instrumented fusion are commendable procedures. We concluded that it
      is a simple, secure, reliable, less-invasive, and well-tolerated technique that
      can successfully resolve this kind of congenital scoliosis in children.

PMID- 30236127
TI  - Integrative analysis of the cancer genome atlas and cancer cell lines
      encyclopedia large-scale genomic databases: MUC4/MUC16/MUC20 signature is
      associated with poor survival in human carcinomas.
AB  - BACKGROUND: MUC4 is a membrane-bound mucin that promotes carcinogenetic
      progression and is often proposed as a promising biomarker for various
      carcinomas. In this manuscript, we analyzed large scale genomic datasets in order
      to evaluate MUC4 expression, identify genes that are correlated with MUC4 and
      propose new signatures as a prognostic marker of epithelial cancers. METHODS:
      Using cBioportal or SurvExpress tools, we studied MUC4 expression in large-scale
      genomic public datasets of human cancer (the cancer genome atlas, TCGA) and
      cancer cell line encyclopedia (CCLE). RESULTS: We identified 187 co-expressed
      genes for which the expression is correlated with MUC4 expression. Gene ontology
      analysis showed they are notably involved in cell adhesion, cell-cell junctions,
      glycosylation and cell signaling. In addition, we showed that MUC4 expression is
      correlated with MUC16 and MUC20, two other membrane-bound mucins. We showed that
      MUC4 expression is associated with a poorer overall survival in TCGA cancers with
      different localizations including pancreatic cancer, bladder cancer, colon
      cancer, lung adenocarcinoma, lung squamous adenocarcinoma, skin cancer and
      stomach cancer. We showed that the combination of MUC4, MUC16 and MUC20 signature
      is associated with statistically significant reduced overall survival and
      increased hazard ratio in pancreatic, colon and stomach cancer. CONCLUSIONS:
      Altogether, this study provides the link between (i) MUC4 expression and clinical
      outcome in cancer and (ii) MUC4 expression and correlated genes involved in cell
      adhesion, cell-cell junctions, glycosylation and cell signaling. We propose the
      MUC4/MUC16/MUC20high signature as a marker of poor prognostic for pancreatic,
      colon and stomach cancers.

PMID- 30236129
TI  - Molecular and cellular characterizations of human cherubism: disease
      aggressiveness depends on osteoclast differentiation.
AB  - BACKGROUND: Cherubism is a rare autosomal dominant disorder of the jaws caused by
      mutation of the SH3BP2 gene. The bone is replaced by a fibrous granuloma
      containing multinucleated giant cells. Cells of the cherubism granuloma have
      never been systematically analyzed. Hence, the aim of this study was to
      characterize the cells in human cherubism granulomas, to determine the
      osteoclastic characteristics of the multinucleated giant cells and to investigate
      the potential role of TNF-alpha in human cherubism. RESULTS: Seven granulomas
      were analyzed in pathology, molecular biology and immunohistochemistry.
      Granulomas were composed mainly of macrophages or osteoclasts within a
      fibroblastic tissue, with few lymphoid cells. Myeloid differentiation and nuclear
      NFATc1 localization were both associated with disease aggressiveness. OPG and
      RANKL immunohistochemical expression was unexpected in our specimens. Five
      granuloma cells were cultured in standard and osteoclastogenic media. In culture,
      cherubism cells were able to differentiate into active osteoclasts, in both
      osteoclastogenic and standard media. IL-6 was the major cytokine present in the
      culture supernatants. CONCLUSION: Multinucleated giant cells from cherubism
      granulomas are CD68 positive cells, which differentiate into macrophages in non
      aggressive cherubism and into osteoclasts in aggressive cherubism, stimulated by
      the NFATc1 pathway. This latter differentiation appears to involve a disturbed
      RANK-L/RANK/OPG pathway and be less TNF-alpha dependent than the cherubism mouse
      model.

PMID- 30236132
TI  - Is minimally invasive superior than open transforaminal lumbar interbody fusion
      for single-level degenerative lumbar diseases: a meta-analysis.
AB  - BACKGROUND: In recent years, the minimally invasive transforaminal lumbar
      interbody fusion (MI-TLIF) is increasingly used to manage the lumbar degenerative
      disease. However, whether MI-TLIF was superior than open transforaminal lumbar
      interbody fusion (O-TLIF) was controversial. The aim of this meta-analysis was to
      compare the clinical outcomes between the MI-TLIF and O-TLIF in single-level
      degenerative lumbar diseases. METHODS: Two reviewers independently searched
      EMBASE, PubMed, Web of Science, and Google database from inception to February
      2018 for studies comparing the MI-TLIF and O-TLIF approach for single-level
      lumbar degenerative disease. The data were extracted and analyzed for primary
      outcomes such as total blood loss, visual analog score (VAS), and other secondary
      outcomes (length of hospital stay, operation time, fluroscopic time, and Oswestry
      Disability Index (ODI)). Meta-analysis was performed by Stata 12.0. RESULTS:
      Seven RCTs were finally included in this meta-analysis. Compared with O-TLIF, MI
      TLIF was associated with significantly less blood loss (weighted mean difference
      (WMD) = - 291.46; 95% confidence interval (CI) - 366.66 to - 216.47; P = 0.000,).
      There was no significant difference between the length of hospital stay,
      postoperative VAS, and ODI. Compared with O-TLIF, MI-TLIF was associated with an
      increase of the fluroscopic time (P < 0.05). CONCLUSION: The MI-TLIF showed
      significantly less blood loss compared with O-TLIF and more fluroscopic time.
      There was no significant difference between the length of hospital stay,
      postoperative VAS, and ODI. More high-quality studies and subsequent meta
      analyses are needed in the future.

PMID- 30236130
TI  - Torquetenovirus detection in exosomes enriched vesicles circulating in human
      plasma samples.
AB  - BACKGROUND: Torquetenovirus (TTV) belongs to Anelloviridae family, infects nearly
      all people indefinitely without causing overt disease establishing a fine and
      successful interaction with the host. Increasing evidence have shown some human
      viruses exploit extracellular vesicles thereby helping viral persistence in the
      host. Here, the presence of TTV in extracellular vesicles circulating in human
      plasma was investigated. METHODS: TTV DNA was quantified in plasma-derived
      exosomes from 122 samples collected from 97 diseased patients and 25 healthy
      donors. Exosomes enriched vesicles (EEVs) were extracted from plasma and
      characterized by Nanoparticle tracking analysis, by western blot for presence of
      tetraspanin CD63, CD81 and annexin II protein and, finally, by electron
      microscopy (EM). Presence and quantitation of TTV DNA were assessed with an
      universal single step real-time TaqMan PCR assay. RESULTS: Preliminary
      investigation showed that the human plasma extracted extracellular vesicles
      exhibited a main size of 70 nm, had concentration of 2.5 * 109/ml, and scored
      positive for tetraspanin CD63, CD81 and annexin II, typical characteristic of the
      exosomes vesicles. EEVs extracted from pooled plasma with TTV DNA viremia of 9.7
      * 104 copies/ml showed to contain 6.3 * 102 TTV copies/ml, corresponding to 0.65%
      of total viral load. Important, TTV yield changed significantly following
      freezing/thawing, detergents and DNAse treatment of plasma before EEVs
      extraction. EEVs purified by sucrose-density gradient centrifugation and analysis
      of gradient fraction positive for exosomes marker CD63 harbored 102 TTV
      copies/ml. Moreover, EM evidenced the presence of TTV-like particles in EEVs.
      Successive investigation of plasma EEVs from 122 subjects (37 HIV-positive, 20
      HCV infected, 20 HBV infected, 20 kidney transplant recipients, and 25 healthy)
      reported TTV DNA detection in 42 (34%) of the viremic samples (37 were from
      diseased patients and 5 from healthy people) at a mean level of 4.8 * 103
      copies/ml. The examination of EEVs selected samples reported the presence of TTV
      genogroup 1, 3, 4 and 5, with genogroup 3 highly observed. CONCLUSIONS:
      Collectively, although these observations should be confirmed by further studies,
      circulation of TTV particles in EEVs opens new avenues and mechanistic insights
      on the molecular strategies adopted by anelloviruses to persist in the host.

PMID- 30236133
TI  - The relationship between the decrease in haemoglobin concentration and the volume
      of fluids administered during resuscitation from septic shock may not be so
      "weak".

PMID- 30236131
TI  - Potent suppression of HIV-1 cell attachment by Kudzu root extract.
AB  - There is a constant need to improve antiretrovirals against HIV since therapy is
      limited by cost, side effects and the emergence of drug resistance. Kudzu is a
      climbing vine from which the root extract (Pueraria lobata), rich in isoflavones
      and saponins, has long been used in traditional Chinese medicine for a variety of
      purposes, from weight loss to alcoholism prevention. Here we show that Kudzu root
      extract significantly inhibits HIV-1 entry into cell lines, primary human CD4+T
      lymphocytes and macrophages, without cell-associated toxicity. Specifically,
      Kudzu inhibits the initial attachment of the viral particle to the cell surface,
      a mechanism that depends on the envelope glycoprotein gp120 but is independent
      from the HIV-1 cell receptor CD4 and co-receptors CXCR4/CCR5. This activity seems
      selective to lentiviruses since Kudzu inhibits HIV-2 and simian immunodeficiency
      virus, but does not interfere with Hepatitis C, Influenza, Zika Brazil and
      adenovirus infection. Importantly, depending on the dose, Kudzu can act
      synergistically or additively with the current antiretroviral cocktails against
      HIV-1 and can block   viruses resistant to the fusion inhibitor Enfuvirtide.
      Together our results highlight Kudzu's root extract value as a supplement to
      current antiretroviral therapy against HIV.

PMID- 30236134
TI  - Gender differences in the use of atypical antipsychotic medications for ICU
      delirium.

PMID- 30236135
TI  - Real-time feedback, debriefing, and retraining system of cardiopulmonary
      resuscitation for out-of-hospital cardiac arrests: a study protocol for a cluster
      parallel-group randomized controlled trial.
AB  - BACKGROUND: The quality of cardiopulmonary resuscitation (CPR) performed by
      emergency medical services (EMS) personnel affects patient outcomes after cardiac
      arrest. A CPR feedback device with an accelerometer mounted on a defibrillator
      can monitor the motion of the patient's sternum to display and record CPR quality
      in real time. To evaluate the utility of real-time feedback, debriefing, and
      retraining using a CPR feedback device outside of the hospital, an open-label,
      cluster randomized controlled trial will be conducted in five municipalities of
      Osaka Prefecture, Japan. METHODS: Each EMS station within a fire department will
      be randomly assigned to: 1) the treatment group with real-time feedback,
      debriefing, and retraining using the CPR feedback device (intervention group); or
      2) the conventional treatment group without real-time feedback, debriefing, and
      retraining (control group). This trial will include 2850 to 3020 patients over
      about 4 years. The primary outcome of the trial is 1-month favorable neurological
      survival, defined as cerebral performance category scale score 1 or 2. Secondary
      outcomes are 1-month survival, survival to hospital discharge, return of
      spontaneous circulation, and quality of CPR including fraction, depth, tempo, and
      ventilation rate. DISCUSSION: The trial will assess whether treatment monitored
      by the CPR feedback device, which allows for real-time feedback, debriefing, and
      retraining using CPR quality data, outperforms conventional treatment without
      real-time feedback, debriefing, and retraining in terms of 1-month favorable
      neurological survival in cardiac arrest patients receiving CPR outside the
      hospital. TRIAL REGISTRATION: University Hospital Medical Information Network
      (UMIN) Clinical Trials Registry, UMIN000021431 . Registered on 11 March 2016.

PMID- 30236136
TI  - Comparing postoperative complication of LigaSure Small Jaw instrument with clamp
      and tie method in thyroidectomy patients: a randomized controlled trial
      [IRCT2014010516077N1].
AB  - BACKGROUND: LigaSure(r) Small Jaw (LSJ) has been recently introduced as an energy
      based vessel sealing device, which has provided better intraoperative and
      postoperative outcomes in thyroidectomies, compared to conventional technique. In
      the current study, we aimed to examine the efficiency of hand-sewn and LSJ
      thyroidectomy, based on operation time and perioperative complications. METHODS:
      All patients with the diagnosis of multinodular goiter, thyroid cancers,
      retrosternal goiter and other indications for thyroid surgeries, enrolled. Of 550
      patients, 261 patients randomly assigned to the conventional group (A) and 274
      patients to LigaSure Small Jaw group (B). Study groups compared concerning
      operative time, recurrent laryngeal nerve (RLN) injury, hypocalcemia, and
      postoperative complications. RESULTS: There was no significant difference
      regarding demographic data between groups A and B. During total thyroidectomy,
      intraoperative blood loss was 64.42 +/- 20.72 ml and 49.64 +/- 17.92 ml in groups
      A and B, respectively (P 0.043). Operative time was significantly lower in LSJ
      group compared to the conventional group in total and subtotal thyroidectomy (P
      0.002; P 0.001). Three patients who underwent conventional total thyroidectomy
      had RLN palsy. However, there was no significant difference between techniques
      regarding RLN injury (P 0.134). Postoperative total and ionized serum calcium
      levels decreased compared to preoperative levels in both conventional and LSJ
      technique; however, changes in total and ionized serum calcium were more severe
      in patients with conventional thyroidectomy (total calcium, P < 0.0001) (ionized
      calcium, P 0.005). CONCLUSION: The LigaSure Small Jaw device decreases operative
      time and intraoperative bleeding compared to conventional technique. Besides,
      changes in total and ionized calcium levels in patients with LSJ thyroidectomy
      are subtle compared to HS technique. TRIAL REGISTRATION: Registered in Iranian
      Registry of Clinical Trials ( www.irct.com ), trial registration:
      IRCT2014010516077N1, Registered: 23 May 2014).

PMID- 30236138
TI  - Studies should fully report on variables that determine the dynamics and the
      temperature gradients during hypothermia.

PMID- 30236137
TI  - Categorization of post-cardiac arrest patients according to the pattern of
      amplitude-integrated electroencephalography after return of spontaneous
      circulation.
AB  - BACKGROUND: Continuous electroencephalography (cEEG), interpreted by an
      experienced neurologist, has been reported to be useful in predicting
      neurological outcome in adult patients post cardiac arrest. Amplitude-integrated
      electroencephalography (aEEG) is a type of quantitative EEG and is easily
      interpreted by a non-neurologist. A few studies have shown the effectiveness of
      aEEG in prognostication among adult patients post cardiac arrest. In this study,
      we hypothesized that the pattern of aEEG after return of spontaneous circulation
      (ROSC) could successfully categorize patients post cardiac arrest according to
      their expected neurological outcome. METHODS: We assessed the comatose survivors
      of out-of-hospital cardiac arrest who received targeted temperature management
      with midazolam-based sedation and were monitored with aEEG at our tertiary
      emergency care center from January 2013 to June 2017. We categorized the patients
      into categories 1 (C1) to 4 (C4). C1 included patients who regained continuous
      normal voltage (CNV) within 12 h post ROSC, C2 included those who recovered CNV
      12-36 h post ROSC, C3 included those who did not recover CNV before 36 h post
      ROSC, and C4 included those who had burst suppression at any time post ROSC. We
      evaluated the outcomes of neurological function for each category at hospital
      discharge. A good outcome was defined as a cerebral performance category of 1 or
      2. RESULTS: A total of 61 patients were assessed (median age, 60 years), among
      whom 42 (70%) had an initial shockable rhythm, and 52 (85%) had cardiac etiology.
      Of all 61 patients, 40 (66%) survived to hospital discharge and 27 (44%) had a
      good neurological outcome. Of 20 patients in C1, 19 (95%) had a good outcome,
      while the percentage dropped to 57% among C2 patients. No patients in C3 or C4
      had a good outcome. Three patients could not be classified into any category.
      CONCLUSIONS: The pattern of aEEG during the early post-cardiac-arrest period can
      successfully categorize patients according to their neurological prognoses and
      could be used as a potential guide to customize post-cardiac-arrest care for each
      patient.

PMID- 30236139
TI  - Integration of multiple types of genetic markers for neuroblastoma may contribute
      to improved prediction of the overall survival.
AB  - BACKGROUND: Modern experimental techniques deliver data sets containing profiles
      of tens of thousands of potential molecular and genetic markers that can be used
      to improve medical diagnostics. Previous studies performed with three different
      experimental methods for the same set of neuroblastoma patients create
      opportunity to examine whether augmenting gene expression profiles with
      information on copy number variation can lead to improved predictions of patients
      survival. We propose methodology based on comprehensive cross-validation
      protocol, that includes feature selection within cross-validation loop and
      classification using machine learning. We also test dependence of results on the
      feature selection process using four different feature selection methods.
      RESULTS: The models utilising features selected based on information entropy are
      slightly, but significantly, better than those using features obtained with t
      test. The synergy between data on genetic variation and gene expression is
      possible, but not confirmed. A slight, but statistically significant, increase of
      the predictive power of machine learning models has been observed for models
      built on combined data sets. It was found while using both out of bag estimate
      and in cross-validation performed on a single set of variables. However, the
      improvement was smaller and non-significant when models were built within full
      cross-validation procedure that included feature selection within cross
      validation loop. Good correlation between performance of the models in the
      internal and external cross-validation was observed, confirming the robustness of
      the proposed protocol and results. CONCLUSIONS: We have developed a protocol for
      building predictive machine learning models. The protocol can provide robust
      estimates of the model performance on unseen data. It is particularly well-suited
      for small data sets. We have applied this protocol to develop prognostic models
      for neuroblastoma, using data on copy number variation and gene expression. We
      have shown that combining these two sources of information may increase the
      quality of the models. Nevertheless, the increase is small and larger samples are
      required to reduce noise and bias arising due to overfitting. REVIEWERS: This
      article was reviewed by Lan Hu, Tim Beissbarth and Dimitar Vassilev.

PMID- 30236140
TI  - Costs, outcome and cost-effectiveness of neurocritical care: a multi-center
      observational study.
AB  - BACKGROUND: Neurocritical illness is a growing healthcare problem with profound
      socioeconomic effects. We assessed differences in healthcare costs and long-term
      outcome for different forms of neurocritical illnesses treated in the intensive
      care unit (ICU). METHODS: We used the prospective Finnish Intensive Care
      Consortium database to identify all adult patients treated for traumatic brain
      injury (TBI), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and
      acute ischemic stroke (AIS) at university hospital ICUs in Finland during 2003
      2013. Outcome variables were one-year mortality and permanent disability. Total
      healthcare costs included the index university hospital costs, rehabilitation
      hospital costs and social security costs up to one year. All costs were converted
      to euros based on the 2013 currency rate. RESULTS: In total 7044 patients were
      included (44% with TBI, 13% with ICH, 27% with SAH, 16% with AIS). In comparison
      to TBI, ICH was associated with the highest risk of death and permanent
      disability (OR 2.6, 95% CI 2.1-3.2 and OR 1.7, 95% CI 1.4-2.1), followed by AIS
      (OR 1.9, 95% CI 1.5-2.3 and OR 1.5, 95% CI 1.3-1.8) and SAH (OR 1.8, 95% CI 1.5
      2.1 and OR 0.8, 95% CI 0.6-0.9), after adjusting for severity of illness. SAH was
      associated with the highest mean total costs (?51,906) followed by ICH (?47,661),
      TBI (?43,916) and AIS (?39,222). Cost per independent survivor was lower for TBI
      (?58,497) and SAH (?96,369) compared to AIS (?104,374) and ICH (?178,071).
      CONCLUSION: Neurocritical illnesses are costly and resource-demanding diseases
      associated with poor outcomes. Intensive care of patients with TBI or SAH more
      commonly result in independent survivors and is associated with lower total
      treatments costs compared to ICH and AIS.

PMID- 30236141
TI  - Circular RNA F-circEA-2a derived from EML4-ALK fusion gene promotes cell
      migration and invasion in non-small cell lung cancer.
AB  - Oncogenic fusion gene Echinoderm Microtubule-associated protein-Like 4-Anaplastic
      Lymphoma Kinase (EML4-ALK) contributes to tumorigenesis of a subset of non-small
      cell lung cancer (NSCLC). Recently, we demonstrated that F-circEA-4a, a tumor
      promoting circular RNA (circRNA) generated from the back-splicing of EML4-ALK
      variant 3b (v3b), is a novel liquid biopsy biomarker for NSCLC. However, circRNAs
      produced from EML4-ALK gene and their roles in NSCLC are not well-characterized.
      Here, we identify another EML4-ALK-v3b-derived circRNA, F-circEA-2a, harboring
      "AA" (rather than "AAAA" in F-circEA-4a) motif at the junction site. F-circEA-2a
      mainly locates in the cytoplasm and promotes cell migration and invasion, but has
      little effect on cell proliferation. Moreover, F-circEA-2a exists in tumor, but
      not in the plasma of NSCLC patients with EML4-ALK fusion gene, further supporting
      the significant diagnostic value of F-circEA-4a for EML4-ALK-positive NSCLC. This
      work finds a novel oncogenic circRNA generated from EML4-ALK fusion gene,
      highlighting the pivotal role of circRNA in EML4-ALK-positive NSCLC development.

PMID- 30236144
TI  - Spectrophotometric analysis of lipid used to examine the phenology of the tick
      Ixodes ricinus.
AB  - BACKGROUND: Ticks store lipid as an energy souce, which depletes progressively
      between blood meals. The amount of lipid and rate of lipid depletion can be used
      as a good indicator of the feeding history and assist in explaining the phenology
      of tick populations. However, existing gravimetric approaches to lipid
      measurement are relatively imprecise. To improve our ability to accurately
      measure lipid accumulation and metabolism in individual ticks, a microquantity
      colorimetric sulfophosphovanillan method of lipid estimation was standardised and
      used to explore the seasonal variations in the lipid content of I. ricinus
      nymphs. RESULTS: Lipid values for field-derived questing ticks, collected by
      blanket dragging, varied between 5-45 MUg and clear patterns of lipid depletion
      were demonstrated under controlled laboratory conditions. For field populations
      collected monthly over two years, the results indicate that two different cohorts
      of nymphs enter the questing tick population in autumn and spring, with very few
      nymphs joining the population in summer. CONCLUSIONS: The data illustrate the
      seasonal change in lipid content of nymphal ticks, reflecting their feeding
      history and highlight the utility of the spectrophotometric technique for
      analysis of lipid in ticks in helping to improve our understanding of seasonal
      activity patterns.

PMID- 30236143
TI  - Epidemiology of Taenia saginata taeniosis/cysticercosis: a systematic review of
      the distribution in the Americas.
AB  - BACKGROUND: The distribution of Taenia saginata in the Americas is unclear.
      Establishing the distribution, economic burden, and potentials for control of
      bovine cysticercosis is increasingly important due to the growing demand for
      beef. This paper aims to take the first step and reviews the recent distribution
      of T. saginata taeniosis and bovine cysticercosis on a national level within the
      Americas. METHODS: We undertook a systematic review of published and grey
      literature for information on the occurrence, prevalence, and geographical
      distribution of bovine cysticercosis and human taeniosis in the 54 countries and
      territories of the Americas between January 1st, 1990 and December 31st, 2017.
      Data on bovine cysticercosis from OIE reports from 1994 to 2005 were also
      included. RESULTS: We identified 66 papers from the Americas with data on the
      occurrence of taeniosis or bovine cysticercosis and an additional 19 OIE country
      reports on bovine cysticercosis. Taeniosis was reported from 13 countries, with
      nine of these countries reporting specifically T. saginata taeniosis, and four
      countries reporting non-species specific taeniosis. The reported prevalence of
      taeniosis ranged between 0.04-8.8%. Bovine cysticercosis was reported from 19
      countries, nine identified through the literature search, and an additional 10
      identified through the OIE country reports for notifiable diseases. The reported
      prevalence of bovine cysticercosis ranged between 0.1-19%. Disease occurrence was
      restricted to 21 countries within the Americas, the majority from the mainland,
      with the only island nations reporting either bovine cysticercosis or taeniosis
      being Cuba, Haiti, and the US Virgin Islands. CONCLUSIONS: Taenia saginata is
      widely distributed across 21 of the 54 countries in the Americas, but
      insufficient epidemiological data are available to estimate the subnational
      spatial distribution, prevalence, incidence and intensity of infections. This
      needs to be addressed through active surveillance and disease detection
      programmes. Such programmes would improve the data quantity and quality, and may
      enable estimation of the economic burden due to bovine cysticercosis in the
      region in turn determining the requirement for and cost-effectiveness of control
      measures.

PMID- 30236142
TI  - Integrated genomic analyses in PDX model reveal a cyclin-dependent kinase
      inhibitor Palbociclib as a novel candidate drug for nasopharyngeal carcinoma.
AB  - BACKGROUND: Patient-derived xenograft (PDX) tumor model has become a new approach
      in identifying druggable tumor mutations, screening and evaluating personalized
      cancer drugs based on the mutated targets. METHODS: We established five
      nasopharyngeal carcinoma (NPC) PDXs in mouse model. Subsequently, whole-exome
      sequencing (WES) and genomic mutation analyses were performed to search for
      genetic alterations for new drug targets. Potential drugs were applied in two NPC
      PDX mice model to assess their anti-cancer activities. RNA sequencing and
      transcriptomic analysis were performed in one NPC PDX mice to correlate with the
      efficacy of the anti-cancer drugs. RESULTS: A relative high incident rate of copy
      number variations (CNVs) of cell cycle-associated genes. Among the five NPC-PDXs,
      three had cyclin D1 (CCND1) amplification while four had cyclin-dependent kinase
      inhibitor CDKN2A deletion. Furthermore, CCND1 overexpression was observed in >
      90% FFPE clinical metastatic NPC tumors (87/91) and was associated with poor
      outcomes. CNV analysis disclosed that plasma CCND1/CDKN2A ratio is correlated
      with EBV DNA load in NPC patients' plasma and could serve as a screening test to
      select potential CDK4/6 inhibitor treatment candidates. Based on our NPC PDX
      model and RNA sequencing, Palbociclib, a cyclin-dependent kinase inhibitor,
      proved to have anti-tumor effects by inducing G1 arrest. One NPC patient with
      liver metastatic was treated with Palbociclib, had stable disease response and a
      drop in Epstein Barr virus (EBV) EBV titer. CONCLUSIONS: Our integrated
      information of sequencing-based genomic studies and tumor transcriptomes with
      drug treatment in NPC-PDX models provided guidelines for personalized precision
      treatments and revealed a cyclin-dependent kinase inhibitor Palbociclib as a
      novel candidate drug for NPC.

PMID- 30236146
TI  - An audit to evaluate an institute's lead researchers' knowledge of trial
      registries and to investigate adherence to data transparency issues in an Italian
      research institute registry.
AB  - BACKGROUND: Clinical trial registries have been a priority topic in the past few
      years in promoting data transparency and accountability. In this context, in
      2011, the IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" set up a
      registry to collect data on all studies in which the institute's researchers are
      involved. In this study we present a self-audit in order to detect the lead
      researchers' general knowledge on registries, the completeness and quality of the
      randomized controlled trial (RCT) data inputted in an Italian research
      institute's registry, and the researchers' adherence to both registration
      requirements and the institute transparency goal, aiming to improve standards and
      leading to greater awareness of the issues involved. METHODS: A questionnaire
      based audit was conducted. To interview researchers we included questions ranging
      from general knowledge on registries (e.g., what are the aims of registries?) to
      questions about their knowledge of the Mario Negri's registry, questions on
      selected trials and registration, included information on the protocol, and the
      results. RESULTS: The audit sample covers 12 of the 47 RCTs at the institute's
      Milan branch, representing all the possible lead researchers responsible for RCTs
      at the institute. The researchers have more than a basic knowledge of trial
      registries and their aims. All the researchers reported that they know of the
      ClinicalTrials.gov registry and most of them reported that they frequently use
      it; however, only a few know about the World Health Organization's registry
      platform (International Clinical Trials Registry Platform). The most cited
      registry aims reported were increased transparency and reduced publication bias.
      Of the studies registered in the institute's registry, 92% had at least one data
      item missing in the registry record. Concerning trial registration in the
      international registries, all 12 respondents said their trial had been registered
      and specified the registry name, but often they had not inputted the associated
      trial ID code in the corresponding field of the institute's registry. Concerning
      two important issues on data transparency and ethical standards, namely
      registration timing and result reporting, 11 stated that their trial was
      registered before starting recruitment, and for five of six closed trials they
      stated that their results have been already published-for one trial within 1 year
      after its completion. CONCLUSIONS: Researchers should guarantee correct reporting
      of trials and their data as a rule of great ethical value. Institutional self
      audits should be performed periodically in order to improve clinical trial
      disclosure.

PMID- 30236145
TI  - "I just want to get better": experiences of children and youth with juvenile
      idiopathic arthritis in a home-based exercise intervention.
AB  - BACKGROUND: Physical activity is essential for ensuring optimal physical function
      and fitness in children with juvenile idiopathic arthritis (JIA). Although
      exercise intervention trials informed current clinical practice, few studies
      addressed why children with JIA do or do not participate in exercise
      interventions. We aimed to describe perceived barriers and facilitators to the
      uptake and adherence to a 6-month home-based exercise intervention for children
      diagnosed with JIA and their parents. METHODS: A convenience sample of children
      (n = 17) and their parents (n = 17) were recruited from a group of 23 child
      parent dyads participating in an exercise intervention study; the Linking
      Exercise, Activity and Pathophysiology Exercise Intervention (LEAP-EI) study.
      Child-parent dyads completed in-depth semi-structured one-to-one interviews with
      a trained interview moderator prior to starting the exercise program and 11 dyads
      completed follow-up interviews at the end of the 6-month program. We also
      conducted 'exit' interviews with one child-parent dyad, one child and one parent
      following three participants' withdrawal from the exercise intervention.
      Interviews were transcribed and transcripts were analyzed using a five-step
      framework analysis to categorize data into themes. RESULTS: Thematic analysis of
      pre-exercise program interview transcripts revealed three reasons child-parent
      dyads initiated the exercise program: 1) potential health benefits, 2)
      selflessness and 3) parental support. Analysis of post-exercise intervention
      transcripts identified four main themes within a priori themes of barriers and
      facilitators to program adherence (median of 46.9%; 5.4, 66.7 IQR): 1) parental
      support, 2) enjoyment, 3) time pressures (subthemes: time requirement of
      exercise, scheduling, forgetting) and 4) physical ailments. CONCLUSION: Major
      barriers to and facilitators to exercise for children with JIA fell into three
      categories: personal, social and programmatic factors. These barriers were not
      unlike those that emerged in previous exercise intervention trials with healthy
      children and youth. There is a need to develop effective strategies to engage
      children in physical activity and to overcome barriers that prevent them from
      doing so. Future initiatives may potentially engage children in developing
      solutions to enhance their participation in and commitment to physical activity.

PMID- 30236147
TI  - Distribution and genetic diversity of Blastocystis subtypes in various mammal and
      bird species in northeastern China.
AB  - BACKGROUND: Blastocystis is one of the most common intestinal parasites in humans
      and animals worldwide. At least 17 subtypes have been identified in mammals and
      birds. In China, although some studies have reported the occurrence of
      Blastocystis in humans and animals, our understanding of the role of animals in
      the transmission of human blastocystosis is only superficial due to a paucity of
      available molecular data. The aim of the present study was to understand
      infection rates of Blastocystis and the distribution and genetic diversity of
      subtypes in various mammal and bird species in northeastern China, as well as to
      assess the zoonotic potential of Blastocystis isolates. METHODS: A total of 1265
      fresh fecal specimens (1080 from ten mammal species and 185 from eight bird
      species) were collected in Heilongjiang, Liaoning and Jilin provinces of China.
      Each specimen was examined for the presence of Blastocystis by PCR amplification
      and sequence analysis of the partial SSU rRNA gene. RESULTS: Fifty-four specimens
      (4.3%) were positive for Blastocystis. Birds (7.0%) had a higher infection rate
      of Blastocystis than mammals (3.8%). Blastocystis was found in seven mammal
      species, reindeer (6.7%), sika deer (14.6%), racoon dogs (7.5%), Arctic foxes
      (1.9%), dogs (2.9%), rats (3.7%) and rabbits (3.3%), as well as three bird
      species, pigeons (2.1%), chickens (13.0%) and red crowned cranes (14.0%). Eight
      subtypes were identified including ST1 (n = 5), ST3 (n = 3), ST4 (n = 13), ST6 (n
      = 8), ST7 (n = 6), ST10 (n = 13), ST13 (n = 4) and ST14 (n = 2). 64.8% (35/54) of
      Blastocystis isolates belonged to potentially zoonotic subtypes. CONCLUSIONS: To
      our knowledge, this is the first report of Blastocystis in reindeer (ST10 and
      ST13), rabbits (ST4), racoon dogs (ST3) and Arctic foxes (ST1, ST4 and ST7). The
      findings of potentially zoonotic subtypes suggest that the animals infected with
      Blastocystis might pose a threat to human health. These data will improve our
      understanding of the host range and genetic diversity of Blastocystis, and also
      help develop efficient control strategies to intervene with and prevent the
      occurrence of human blastocystosis in the investigated areas.

PMID- 30236149
TI  - Tai chi for overweight/obese adolescent and young women with polycystic ovary
      syndrome: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Tai Chi is a moderately intense exercise that dates back to ancient
      China. It has been reported that Tai Chi not only has beneficial effects on
      metabolic disorders, such as diabetes, cardiovascular diseases and obesity, but
      also has favorable effects on psychological well-being. Since these conditions
      are quite closely associated with polycystic ovary syndrome (PCOS), we hypothesis
      that Tai Chi could be a potential treatment option for PCOS patients. We aim to
      determine the feasibility and effectiveness of Tai Chi on overweight/obese
      adolescent and young women with PCOS. METHODS: A total of 50 patients will be
      randomized into two arms: (1) Tai Chi or (2) self-monitored exercise. Both groups
      will exercise for 3 months. The primary hypothesis is that Tai Chi results in a
      significantly lower Body Mass Index (BMI) than self-monitored exercise. The study
      was approved by the Ethics Committee of the First Affiliated Hospital of
      Heilongjiang University of Chinese Medicine. DISCUSSION: This is the first study
      to determine the feasibility and effectiveness of Tai Chi in treating
      overweight/obese adolescent and young women with PCOS. The trial will provide
      evidence to assess the feasibility of a future multicenter, randomized controlled
      trial. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02608554 . Registered on 17
      November 2015.

PMID- 30236148
TI  - Culex tarsalis is a competent vector species for Cache Valley virus.
AB  - BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne orthobunyavirus endemic
      in North America. The virus is an important agricultural pathogen leading to
      abortion and embryonic lethality in ruminant species, especially sheep. The
      importance of CVV in human public health has recently increased because of the
      report of severe neurotropic diseases. However, mosquito species responsible for
      transmission of the virus to humans remain to be determined. In this study,
      vector competence of three Culex species mosquitoes of public health importance,
      Culex pipiens, Cx. tarsalis and Cx. quinquefasciatus, was determined in order to
      identify potential bridge vector species responsible for the transmission of CVV
      from viremic vertebrate hosts to humans. RESULTS: Variation of susceptibility to
      CVV was observed among selected Culex species mosquitoes tested in this study.
      Per os infection resulted in the establishment of infection and dissemination in
      Culex tarsalis, whereas Cx. pipiens and Cx. quinquefasciatus were highly
      refractory to CVV. Detection of viral RNA in saliva collected from infected Cx.
      tarsalis provided evidence supporting its role as a competent vector.
      CONCLUSIONS: Our study provided further understanding of the transmission cycles
      of CVV and identifies Cx. tarsalis as a competent vector.

PMID- 30236150
TI  - Genetic characterisation and phylogenetic status of whipworms (Trichuris spp.)
      from captive non-human primates in China, determined by nuclear and mitochondrial
      sequencing.
AB  - BACKGROUND: Whipworms (Nematoda: Trichuridae), among the most common soil
      transmitted helminths (STHs), can cause the socioeconomically important disease
      trichuriasis in various mammalian hosts including humans and non-human primates.
      For many years, Trichuris from non-human primates has been assigned to the same
      species as the one infecting humans Trichuris trichiura. More recently, several
      molecular reports challenged this assumption following recognition of a Trichuris
      species complex observed in humans and non-human primates. A refined concept for
      species limits within Trichuris contributes to an understanding of diversity and
      the potential (zoonotic) transmission among humans and non-human primates. In
      this study, we expanded previous investigations by exploring the diversity of
      Trichuris among eight primates including three Asian autochthonous species (i.e.
      Rhinopithecus roxellana, Rhinopithecus bieti and Nomascus leucogenys). Species
      level identification, whether novel or assignable to known lineages of Trichuris,
      was based on analyses of nuclear internal transcribed spacers (ITS) and
      mitochondrial cytochrome c oxidase subunit 1 (cox1) genes. RESULTS: In total,
      seven genetically distinct subgroups of whipworms were determined to be present
      among the primates sampled. Most Trichuris lineages, including Subgroups 1, 1',
      3, 5 and 6, showed a broad host range and were not restricted to particular
      primate species; in addition to T. trichiura, a complex of Trichuris species was
      shown infecting primates. Furthermore, it was assumed that Trichuris spp. from
      either N. leucogenys and P. hamadryas or R. roxellana and R. bieti, respectively,
      were conspecific. Each pair was indicated to be a discrete lineage of Trichuris,
      designated, respectively, as Subgroups 1 or 1' and 2, based on integrated genetic
      and phylogenetic evidence. CONCLUSION: These results emphasise that the taxonomy
      and genetic variations of Trichuris are more complicated than previously
      acknowledged. These cumulative molecular and phylogenetic data provide a better
      understanding of the taxonomy, genetics and evolutionary biology of the
      whipworms.

PMID- 30236151
TI  - Targeted gluteal exercise versus sham exercise on self-reported physical function
      for people with hip osteoarthritis (the GHOst trial - Gluteal exercise for Hip
      Osteoarthritis): a protocol for a randomised clinical trial.
AB  - BACKGROUND: Clinical practice guidelines recommend exercise as the first line of
      management for hip osteoarthritis, yet high-quality evidence from Cochrane
      reviews suggest only slight benefits for pain and physical function; and no
      benefit on quality of life (low-quality evidence). However, the scope of physical
      impairments identified in people with hip osteoarthritis may not have been
      adequately addressed with targeted rehabilitation options in previous randomised
      controlled trials (RCTs). Potential targeted options include gait retraining to
      address spatio-temporal impairments in walking; motor control training to address
      deep gluteal (gluteus minimus) dysfunction; and progressive, high-intensity
      resistance exercises to address atrophy of the gluteal muscles. The aim of this
      study is to investigate the effect of a targeted gluteal rehabilitation programme
      that incorporates gait retraining, motor control and progressive, high-intensity
      resistance-strength training, to address physical activity levels and self
      reported physical function in people with mild to moderate disability from hip
      osteoarthritis. METHODS: Ninety people diagnosed with mild to moderately
      disabling hip osteoarthritis will be recruited and randomised to receive one of
      two exercise programmes (sham or GHOst programme). Interventions will be 12 weeks
      in duration, with weekly, supervised physiotherapy sessions, and daily home
      exercises. Both groups will receive standardised education. Outcomes will be
      assessed at baseline, 7 weeks, 13 weeks (primary time-point) and 25 weeks. The
      primary outcome will be self-reported physical function measured with the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary
      outcomes include physical activity measured with a tri-axial accelerometer,
      physical function tests, self-reported physical activity, isometric hip-muscle
      strength tests, hip-related patient-reported outcome measures, pain thoughts and
      depressive symptoms, quality of life, global rating of change, gluteal-muscle
      activity (electromyography (EMG)) and gluteal-muscle size and adiposity (magnetic
      resonance imaging (MRI)). DISCUSSION: This will be the first study to compare a
      targeted gluteal rehabilitation programme to a sham exercise programme. The
      targeted GHOst programme includes exercises designed to address gait impairments
      as well as gluteal-muscle atrophy and dysfunction. TRIAL REGISTRATION: Australian
      New Zealand Clinical Trials Registry, ID: ACTRN12617000970347 . Registered
      retrospectively on 5 July 2017. Protocol version 3.0.

PMID- 30236152
TI  - 1,25(OH)2D3 and dexamethasone additively suppress synovial fibroblast activation
      by CCR6+ T helper memory cells and enhance the effect of tumor necrosis factor
      alpha blockade.
AB  - BACKGROUND: Despite recent improvements in the treatment of rheumatoid arthritis
      (RA), an insufficient treatment response and the development of treatment
      resistance in many patients illustrates the need for new therapeutic strategies.
      Chronic synovial inflammation could be suppressed by targeting RA synovial
      fibroblast (RASF) activation by, for example, interleukin (IL)-17A-producing
      CCR6+ T helper memory (memTh) cells. Here, we modulated this interaction by
      combining the active vitamin D metabolite 1,25(OH)2D3 with dexamethasone (DEX)
      and explored the potential therapeutic applications. METHODS: CCR6+ memTh cells
      from peripheral blood mononuclear cells (PBMCs) of healthy donors or treatment
      naive early RA patients were cultured alone or with RASF from established RA
      patients for 3 days and treated with or without 1,25(OH)2D3, DEX, or etanercept.
      Treatment effects were assessed using enzyme-linked immunosorbent assay (ELISA)
      and flow cytometry. RESULTS: 1,25(OH)2D3, and to lesser extent DEX, reduced
      production of the pro-inflammatory cytokines IL-17A, IL-22, and interferon
      (IFN)gamma in CCR6+ memTh cells. Tumor necrosis factor (TNF)alpha was only
      inhibited by the combination of 1,25(OH)2D3 and DEX. In contrast, DEX was the
      strongest inhibitor of IL-6, IL-8, and tissue-destructive enzymes in RASF. As a
      result, 1,25(OH)2D3 and DEX additively inhibited inflammatory mediators in CCR6+
      memTh-RASF cocultures. Interestingly, low doses of mainly DEX, but also
      1,25(OH)2D3, combined with etanercept better suppressed synovial inflammation in
      this coculture model compared with etanercept alone. CONCLUSION: This study
      suggests that 1,25(OH)2D3 and DEX additively inhibit synovial inflammation
      through targeting predominantly CCR6+ memTh cells and RASF, respectively.
      Furthermore, low doses of DEX and 1,25(OH)2D3 enhance the effect of TNFalpha
      blockade in inhibiting RASF activation, thus providing a basis to improve RA
      treatment.

PMID- 30236154
TI  - Gender differences in the comprehension of care plans in an emergency department
      setting.
AB  - BACKGROUND: Previous studies have shown that, in a variety of health care
      settings, patients often do not understand what health care professionals tell
      them about their diagnoses and care plans; this is particularly true among male
      patients. Emergency department (ED) settings present unique challenges to
      communication with patients due to the rapid pace of activity, substantial
      changes in personnel over the course of the day and the week, and the need for
      fast decision-making processes. The aim of our study was to investigate the
      extent to which patients in an Israeli ED comprehended their plan of care and
      whether there were gender differences in this regard. METHODS: We conducted a
      questionnaire-based prospective study, in which patients admitted to the ED at
      Rabin Medical Center were evaluated during the years 2014-2016. The primary
      outcome was patients' comprehension of their plan of care, stratified by gender
      of patients. Plan of care included information related to diagnosis, treatment
      and discharge instructions. The secondary outcome was patients' satisfaction with
      the instruction process. RESULTS: One hundred seventy seven ED patients met study
      criteria and were asked to participate in the study; 85% of them agreed to do so.
      Overall, 150 ED patients aged 18-80 were recruited [75 men (50%) and 75 women
      (50%)]. 80% of the respondents reported a satisfactory understanding of their
      plan of care. Overall, no gender-related differences were found. Differences
      between men and women concerning satisfaction with the instructions provided by
      nurses were found among non-Hebrew speakers, but not among Hebrew speakers.
      CONCLUSION: Contrary to most earlier studies, patients at our ED demonstrated a
      high degree of self-reported adequate comprehension concerning their plan of
      care, and overall no gender-related differences were found. These finding may be
      due in part to improved training of the medical staff to better communicate with
      the patients and to answer their questions. In addition, patients may feel more
      comfortable than in the past about asking the medical staff questions regarding
      their plan of care and diagnosis. The main implication of this study is that
      physician education programs should continue to emphasize patient-physician
      communications skills and improving methods for providing patients with
      information.

PMID- 30236153
TI  - Single-cell transcriptomics reveal that PD-1 mediates immune tolerance by
      regulating proliferation of regulatory T cells.
AB  - BACKGROUND: We have previously reported an antigen-specific protocol to induce
      transplant tolerance and linked suppression to human embryonic stem cell (hESC)
      derived tissues in immunocompetent mice through coreceptor and costimulation
      blockade. However, the exact mechanisms of acquired immune tolerance in this
      model have remained unclear. METHODS: We utilize the NOD.Foxp3hCD2 reporter mouse
      line and an ablative anti-hCD2 antibody to ask if CD4+FOXP3+ regulatory T cells
      (Treg) are required for coreceptor and costimulation blockade-induced immune
      tolerance. We also perform genome-wide single-cell RNA-sequencing to interrogate
      Treg during immune rejection and tolerance and to indicate possible mechanisms
      involved in sustaining Treg function. RESULTS: We show that Treg are
      indispensable for tolerance induced by coreceptor and costimulation blockade as
      depletion of which with an anti-hCD2 antibody resulted in rejection of hESC
      derived pancreatic islets in NOD.Foxp3hCD2 mice. Single-cell transcriptomic
      profiling of 12,964 intragraft CD4+ T cells derived from rejecting and tolerated
      grafts reveals that Treg are heterogeneous and functionally distinct in the two
      outcomes of transplant rejection and tolerance. Treg appear to mainly promote
      chemotactic and ubiquitin-dependent protein catabolism during transplant
      rejection while seeming to harness proliferative and immunosuppressive function
      during tolerance. We also demonstrate that this form of acquired transplant
      tolerance is associated with increased proliferation and PD-1 expression by Treg.
      Blocking PD-1 signaling with a neutralizing anti-PD-1 antibody leads to reduced
      Treg proliferation and graft rejection. CONCLUSIONS: Our results suggest that
      short-term coreceptor and costimulation blockade mediates immune tolerance to
      hESC-derived pancreatic islets by promoting Treg proliferation through engagement
      of PD-1. Our findings could give new insights into clinical development of hESC
      derived pancreatic tissues, combined with immunotherapies that expand intragraft
      Treg, as a potentially sustainable alternative treatment for T1D.

PMID- 30236156
TI  - False negative computed tomography scan due to pelvic binder in a patient with
      pelvic disruption: a case report and review of the literature.
AB  - BACKGROUND: Pelvic binders are routinely used in the prehospital setting for
      stabilization of pelvic injuries in patients with trauma. Emergency department
      trauma management relies on primary and secondary survey assessment and imaging,
      most often computed tomography, in hemodynamically stable patients. Maintaining
      the pelvic binder in situ allows stabilization of pelvic injuries during imaging
      but may hinder the visualization of some pelvic lesions. We report a very rare
      case of severe pelvic disruption with an absolutely normal computed tomography
      scan due to the effective placement of a pelvic binder. CASE PRESENTATION: We
      report the case of a 49-year-old Caucasian man referred to our Emergency
      Department after a high velocity motorcycle accident. Primary assessment revealed
      a left wrist deformation and pelvic pain, and a pelvic binder was applied by
      paramedics. A total body computed tomography scan was performed after arrival in
      our Emergency Department and did not reveal any pelvic injury. The pelvic binder
      was removed and because of persisting symphyseal pain, pelvic plain radiography
      was performed revealing a pelvic disruption with an opening of the pubic
      symphysis and of the left sacroiliac joint ("open book" type pelvic injury)
      requiring surgical stabilization. CONCLUSIONS: Pelvic binders may mask pelvic
      disruption in patients with trauma. Pelvic plain radiography should be repeated
      after pelvic binder removal in patients with high velocity trauma and pelvic
      symptoms or neurological alterations limiting the reliability of clinical
      examination.

PMID- 30236155
TI  - Enhancement of insect susceptibility and larvicidal efficacy of Cry4Ba toxin by
      calcofluor.
AB  - BACKGROUND: Mosquitoes transmit many vector-borne infectious diseases including
      malaria, dengue, chikungunya, yellow fever, filariasis, and Japanese
      encephalitis. The insecticidal delta-endotoxins Cry4, Cry11, and Cyt produced
      from Bacillus thuringiensis have been used for bio-control of mosquito larvae.
      Cry delta-endotoxins are synthesised as inactive protoxins in the form of
      crystalline inclusions in which they are processed to active toxins in larval
      midgut lumen. Previously, we demonstrated that the activated Cry4Ba toxin has to
      alter the permeability of the peritrophic membrane (PM), allowing toxin passage
      across PM to reach specific receptors on microvilli of larval midgut epithelial
      cells, where the toxin undergoes conformational changes, followed by membrane
      insertion and pore formation, resulting in larval death. A peritrophic membrane
      (PM)-binding calcofluor has been proposed to inhibit chitin formation and enhance
      baculovirus infection of lepidopteran Trichoplusia ni. METHODS: In this study,
      Aedes aegypti larvae were fed with the calcofluor and Cry4Ba toxin to investigate
      the effect of this agent on the toxicity of the Cry4Ba toxin. RESULTS: Calcofluor
      displayed an enhancing effect when co-fed with the Cry4Ba wild-type toxin. The
      agent could restore the killing activity of the partially active Cry4Ba mutant
      E417A/Y455A toward Ae. aegypti larvae. PM destruction was observed after larval
      challenge with calcofluor together with the toxin. Interestingly, calcofluor
      increased Cry4Ba toxin susceptibility toward semi-susceptible Culex
      quinquefasciatus larvae. However, calcofluor alone or in combination with the
      toxin showed no mortality effect on non-susceptible fresh-water fleas, Moina
      macrocopa. CONCLUSIONS: Our results suggest that PM may contribute to the
      resistance of the mosquito larvae to Cry4Ba toxin. The PM-permeability
      alternating calcofluor might be a promising candidate for enhancing insect
      susceptibility, which will consequently improve Cry4Ba efficacy in field settings
      in the future.

PMID- 30236157
TI  - Promoting patient comprehension of relevant health information.
AB  - Patient understanding of health care recommendations provided by health care
      professionals is essential to enabling active and informed patient participation
      in care. Unfortunately, evidence suggests that patients often seriously
      misunderstand relevant health information provided to them, leading to errant
      patient decisions about their care. This commentary examines key communication
      factors that influence patient understanding and argues for a comprehensive
      approach to assessing and promoting patient comprehension.

PMID- 30236158
TI  - Grazing-induced microbiome alterations drive soil organic carbon turnover and
      productivity in meadow steppe.
AB  - BACKGROUND: Grazing is a major modulator of biodiversity and productivity in
      grasslands. However, our understanding of grazing-induced changes in below-ground
      communities, processes, and soil productivity is limited. Here, using a long-term
      enclosed grazing meadow steppe, we investigated the impacts of grazing on the
      soil organic carbon (SOC) turnover, the microbial community composition,
      resistance and activity under seasonal changes, and the microbial contributions
      to soil productivity. RESULTS: The results demonstrated that grazing had
      significant impacts on soil microbial communities and ecosystem functions in
      meadow steppe. The highest microbial alpha-diversity was observed under light
      grazing intensity, while the highest beta-diversity was observed under moderate
      grazing intensity. Grazing shifted the microbial composition from fungi dominated
      to bacteria dominated and from slow growing to fast growing, thereby resulting in
      a shift from fungi-dominated food webs primarily utilizing recalcitrant SOC to
      bacteria-dominated food webs mainly utilizing labile SOC. Moreover, the higher
      fungal recalcitrant-SOC-decomposing activities and bacterial labile-SOC
      decomposing activities were observed in fungi- and bacteria-dominated
      communities, respectively. Notably, the robustness of bacterial community and the
      stability of bacterial activity were associated with alpha-diversity, while this
      was not the case for the robustness of fungal community and its associated
      activities. Finally, we observed that microbial alpha-diversity rather than SOC
      turnover rate can predict soil productivity. CONCLUSIONS: Our findings indicate
      the strong influence of grazing on soil microbial community, SOC turnover, and
      soil productivity and the important positive role of soil microbial alpha
      diversity in steering the functions of meadow steppe ecosystems.

PMID- 30236159
TI  - Interaction between CD177 and platelet endothelial cell adhesion molecule-1
      downregulates membrane-bound proteinase-3 (PR3) expression on neutrophils and
      attenuates neutrophil activation induced by PR3-ANCA.
AB  - BACKGROUND: A recent study found that CD177 served as a receptor of membrane
      bound proteinase-3 (mPR3) in a subset of neutrophils. Furthermore, CD177 has been
      identified as a high-affinity heterophilic binding partner for the endothelial
      cell platelet endothelial cell adhesion molecule-1 (PECAM-1). The current study
      aimed to investigate whether the interaction between PECAM-1 and CD177 could
      influence mPR3 expression as well as PR3-antineutrophil cytoplasmic antibody
      (ANCA)-induced neutrophil activation and glomerular endothelial cell (GEnC)
      injury. METHODS: The effect of interaction between CD177 and PECAM-1 on mPR3
      expression was explored by enzyme-linked immunosorbent assay (ELISA) and flow
      cytometry. The effect of PECAM-1 on neutrophil activation and GEnC injury induced
      by PR3-ANCA-positive immunoglobulin (Ig)Gs was evaluated by dihydrorhodamine
      (DHR) assay and ELISA. CD177-negative neutrophils were selected by magnetic cell
      sorting (MACS), and the inhibitory effect of PECAM-1 on CD177-negative and mixed
      neutrophils was explored by measuring neutrophil degranulation. RESULTS: The
      level of specific interaction between CD177 and PECAM-1 was elevated with
      increasing CD177 concentration. The expression of mPR3 significantly decreased in
      neutrophils preincubated with PECAM-1 in a dose-dependent manner. Consistently,
      the levels of respiratory burst and degranulation induced by PR3-ANCA-positive
      IgGs in recombinant human tumor necrosis factor-alpha (TNF-alpha)-primed
      neutrophils was significantly reduced by preincubation with PECAM-1 (440.6 +/-
      123.0 vs. 511.4 +/- 95.5, p < 0.05; and 3155.0 +/- 1733.0 ng/ml vs. 5903.0 +/-
      717.5 ng/ml, p < 0.05, respectively). In CD177-negative neutrophils incubated
      with PR3-ANCA-positive IgGs, the level of degranulation was not significantly
      changed by preincubation with PECAM-1. However, in mixed neutrophils, PECAM-1
      significantly decreased the level of degranulation induced by PR3-ANCA-positive
      IgGs (1015.9 +/- 229.2% vs. 1725.2 +/- 412.4%, p < 0.01). Furthermore, with
      preincubation of TNF-alpha-primed neutrophils with PECAM-1, the level of soluble
      intercellular cell adhesion molecule-1 (sICAM-1), a marker of endothelial cell
      activation and injury, in the supernatant of GEnCs treated with primed
      neutrophils plus PR3-ANCA-positive IgGs was significantly attenuated (112.7 +/-
      24.2 pg/ml vs. 167.5 +/- 27.7 pg/ml, p < 0.05). CONCLUSIONS: PECAM-1 can decrease
      the level of mPR3 expression on neutrophils, resulting in attenuation of
      neutrophil activation and subsequent GEnC injury induced by PR3-ANCA-positive
      IgGs.

PMID- 30236160
TI  - Changes in the immune system in experimental acanthamoebiasis in immunocompetent
      and immunosuppressed hosts.
AB  - BACKGROUND: Acanthamoebiasis is most often found in patients with immune
      deficiency, with infections facilitated by the intake of immunosuppressive drugs.
      The host immune response to Acanthamoeba spp. infection is poorly understood.
      Thus, in this study, we aimed to examine the course of Acanthamoeba spp.
      infection taking into account the host's immunological status, including
      assessment of the hematological parameters, cytokine analysis, immunophenotypic
      changes in spleen populations, and histological spleen changes, which could help
      clarify some aspects of the immune response to acanthamoebiasis. In our
      experimental study, we used Acanthamoeba strain AM 22 isolated from the
      bronchoaspirate of a patient with acute myeloid leukaemia (AML) and atypical
      pneumonia symptoms. RESULTS: Acanthamoeba spp. affected the hematological
      parameters in immunocompetent and immunosuppressed mice and induced a change in
      spleen weight during infection. Moreover, analysis of anti-inflammatory (IL-4 and
      IL-10) and pro-inflammatory (IL-17A and IFN-gamma) cytokines produced by
      splenocytes stimulated with concanavalin A demonstrated that Acanthamoeba spp.
      induced a selective Th1, Th2 and Th17 response at later stages of the infection
      in immunocompetent hosts. In the case of hosts with low immunity, Acanthamoeba
      elicited robust Th1 cell-mediated immunity without the participation of Th17. We
      observed suppression of CD8+ and CD4+ T lymphocytes and CD3+CD4-CD8- double
      negative (DN) T lymphocyte populations in the beginning, and in the case of
      CD3+/CD4+/CD8+ double-positive (DP) T cells in the final phase of Acanthamoeba
      spp. infection in hosts with low immunity. Also, CD4+T lymphocytes and CD3+/CD4+
      and CD3+/CD8+ lymphocyte counts during each stage of acanthamoebiasis were shown
      to be upregulated. CONCLUSIONS: We demonstrated that analysis of the immune
      response and pathogenesis mechanisms of clinical isolates of Acanthamoeba spp. in
      an animal model not only has purely cognitive significance but above all, may
      help in the development of effective methods of pharmacological therapy
      especially in patients with low immunity.

PMID- 30236161
TI  - Transmissible gastroenteritis virus infection decreases arginine uptake by
      downregulating CAT-1 expression.
AB  - Transmissible gastroenteritis virus (TGEV) is a coronavirus that causes severe
      diarrhea in suckling piglets. TGEV primarily targets and infects porcine
      intestinal epithelial cells, which play an important role in nutrient absorption.
      However, the effects of TGEV infection on nutrient absorption in swine have not
      yet been investigated. In this study, we evaluated the impact of TGEV infection
      on arginine uptake using the porcine small intestinal epithelial cell line IPEC
      J2 as a model system. High performance liquid chromatography (HPLC) analyses
      showed that TGEV infection leads to reduced arginine uptake at 48 hours post
      infection (hpi). Expression of cationic amino acid transporter 1 (CAT-1) was
      attenuated as well. TGEV infection induced activation of phospho-protein kinase C
      alpha (p-PKC alpha), phospho-epidermal growth factor receptor (p-EGFR), and
      enhanced the expression of caveolin-1, all of which appear to be involved in down
      regulating arginine uptake and CAT-1 expression. These results illuminate the
      relationship between TGEV infection and nutrient absorption, and further our
      understanding of the mechanisms of TGEV infection.

PMID- 30236162
TI  - The marsupial trypanosome Trypanosoma copemani is not an obligate intracellular
      parasite, although it adversely affects cell health.
AB  - BACKGROUND: Trypanosoma cruzi invades and replicates inside mammalian cells,
      which can lead to chronic Chagas disease in humans. Trypanosoma copemani infects
      Australian marsupials and recent investigations indicate it may be able to invade
      mammalian cells in vitro, similar to T. cruzi. Here, T. cruzi 10R26 strain
      (TcIIa) and two strains of T. copemani [genotype 1 (G1) and genotype 2 (G2)] were
      incubated with marsupial cells in vitro. Live-cell time-lapse and fluorescent
      microscopy, combined with high-resolution microscopy (transmission and scanning
      electron microscopy) were used to investigate surface interactions between
      parasites and mammalian cells. RESULTS: The number of parasites invading cells
      was significantly higher in T. cruzi compared to either genotype of T. copemani,
      between which there was no significant difference. While capable of cellular
      invasion, T. copemani did not multiply in host cells in vitro as there was no
      increase in intracellular amastigotes over time and no release of new
      trypomastigotes from host cells, as observed in T. cruzi. Exposure of host cells
      to G2 trypomastigotes resulted in increased host cell membrane permeability
      within 24 h of infection, and host cell death/blebbing was also observed. G2
      parasites also became embedded in the host cell membrane. CONCLUSIONS:
      Trypanosoma copemani is unlikely to have an obligate intracellular life-cycle
      like T. cruzi. However, T. copemani adversely affects cell health in vitro and
      should be investigated in vivo in infected host tissues to better understand this
      host-parasite relationship. Future research should focus on increasing
      understanding of the T. copemani life history and the genetic, physiological and
      ecological differences between different genotypes.

PMID- 30236163
TI  - Identification and characterization of myocardial metastases in neuroendocrine
      tumor patients using 68Ga-DOTATATE PET-CT.
AB  - BACKGROUND: Focal 68Ga-DOTATATE PET lesions within the myocardium of
      neuroendocrine tumor (NET) patients are observed in clinical practice. We
      determined the frequency and characteristics of lesions that are consistent with
      cardiac metastasis and assessed the lesion detection rate of conventional
      imaging. METHODS: 629 patients who underwent 68Ga-DOTATATE PET-CT at a
      supraregional comprehensive cancer center on NET were included from a consecutive
      registry. Inclusion criteria were: (1) focal 68Ga-DOTATATE tracer uptake within
      the myocardium in more than two sequential PET exams, and (2) contrast-enhanced
      CT. To determine the diagnostic accuracy of conventional CT imaging, a case
      control cohort with a ratio of 1:3 was used. PET and CT were independently
      analyzed by two blinded readers. Cohen's kappa was assessed for interreader
      agreement. Descriptive statistics were applied for frequencies and
      characteristics and group comparisons were analyzed using the Fisher's exact
      test. RESULTS: The prevalence of myocardial metastases related to the registry
      was 2.4% (15 of 629 NET patients fulfilling the inclusion criteria), for a total
      of 21 myocardial 68Ga-DOTATATE foci detected. Myocardial lesions were most
      frequently located in the left ventricle (43%) and the septum (43%). No patient
      demonstrated a pericardial effusion. Patients with myocardial metastases did not
      differ in demographics, tumor grading, disease stage or circulating tumor markers
      compared to the overall registry (all p > 0.05). Higher Ki67-Indices were
      observed (p = 0.049) for patients with myocardial metastases. Interreader
      agreement for PET assessment was excellent (Cohen's kappa = 1.0). CT reading
      showed a sensitivity of 19% (95% confidence interval: 6-43%) at a specificity of
      100% (95% confidence interval: 90-100%). CONCLUSIONS: 68Ga-DOTATATE PET enables
      detection of myocardial metastatic lesions in NET patients. In contrast, standard
      morphologic CT imaging provides very limited sensitivity.

PMID- 30236165
TI  - Effects of chronic heat stress on lactational performance and the transcriptomic
      profile of blood cells in lactating dairy goats.
AB  - High temperature is a major stress that negatively affects welfare, health, and
      productivity of dairy animals. Heat-stressed animals are more prone to disease,
      suggesting that their immunity is hindered. Although productive and physiologic
      responses of dairy animals to heat stress are well known, there is still limited
      information on the response at the transcriptome level. Our objective was to
      evaluate the changes in performance and blood transcriptomics of dairy goats
      under heat stress. Eight multiparous Murciano-Granadina dairy goats in mid
      lactation were assigned to 1 of 2 climatic treatments for 35 d. Treatments and
      temperature-humidity index (THI) were: (1) thermal neutral (TN: n = 4; 15-20 
      degrees C, 40-45%, THI = 59-65), and (2) heat stress (HS: n = 4; 12 h at 37 
      degrees C-40%, THI = 86; 12 h at 30  degrees C-40%, THI = 77). Rectal
      temperature, respiratory rate, feed intake and milk yield were recorded daily.
      Additionally, milk composition was evaluated weekly. Blood samples were collected
      at d 35 and RNA was extracted for microarray analyses (Affymetrix GeneChip Bovine
      Genome Array). Differences in rectal temperature and respiratory rate between HS
      and TN goats were maximal during the first 3 d of the experiment, reduced
      thereafter, but remained significant throughout the 35-d experimental period.
      Heat stress reduced feed intake, milk yield, milk protein and milk fat contents
      by 29, 8, 12, and 13%, respectively. Microarray analysis of blood revealed that
      55 genes were up-regulated, whereas 88 were down-regulated by HS. Bioinformatics
      analysis using the Dynamic Impact Approach revealed that 31 biological pathways
      were impacted by HS. Pathways associated with leukocyte transendothelial
      migration, cell adhesion, hematopoietic cell lineage, calcium signaling, and PPAR
      signaling were negatively impacted by HS, whereas nucleotide metabolism was
      activated. In conclusion, heat stress not only negatively affected milk
      production in dairy goats, but also resulted in alterations in the functionality
      of immune cells, which would make the immune system of heat-stressed goats less
      capable of fending-off diseases.

PMID- 30236166
TI  - Use of whole genome sequencing to complement characterisation of a typhoid fever
      outbreak among a Marshallese community: Oklahoma, 2015.
AB  - Typhoid fever is an illness caused by Salmonella enterica serotype Typhi. In
      developing regions, it affects an estimated 20 million people annually, causing
      200 000 deaths. Although uncommon, cases occur in the USA each year,
      predominantly due to international travel. During February 2015, the Oklahoma
      State Department of Health (OSDH) detected an outbreak of typhoid fever among
      residents of northwestern Oklahoma. OSDH conducted case-patient interviews to
      identify the source and symptomatic contacts. Whole genome sequencing (WGS) was
      performed to characterise the genetic relatedness of isolates among the four
      outbreak-associated pulsed-field gel electrophoresis (PFGE) patterns. We
      identified 38 cases, 25 confirmed and 13 probable, in two states. WGS revealed a
      0-10 single-nucleotide polymorphism variation between isolates. Although we were
      unable to determine the source, almost all case-patients were members of the
      Marshallese community that attended a common event in Oklahoma, or were contacts
      to a confirmed case. This is the largest outbreak of typhoid fever in the USA
      since 1989, and first to apply WGS to complement interpretation of PFGE results
      during a typhoid fever outbreak investigation. This investigation illustrates the
      potential risk of outbreaks among communities comprised of international
      populations from regions where typhoid fever remains endemic.

PMID- 30236164
TI  - First report of Giardia duodenalis infection in bamboo rats.
AB  - BACKGROUND: The zoonotic parasite, Giardia duodenalis (syns. G. lamblia and G.
      intestinalis), has been widely reported in humans and animals, including rodents.
      The bamboo rat, a rodent species belonged to the subfamily Rhizomyinae, is farmed
      in China because of its medicinal and edible values. However, no information of
      G. duodenalis infection was available in bamboo rats prior to the present study.
      Here, the prevalence and genetic diversity of G. duodenalis in bamboo rats from
      Hunan Province of China were investigated. RESULTS: Of 480 faecal samples
      collected from six farms located in four cities (Wugang, Chenzhou, Huaihua and
      Jishou) of Hunan Province, 52 (10.8%) were positive for G. duodenalis infection
      by using a nested PCR approach targeting the beta giardin (bg) gene. Significant
      differences (P < 0.01) in prevalence were found among different age groups and
      geographical localities, and among different farms in Wugang city. Sequence
      analysis revealed existence of the zoonotic assemblage B and genetic diversity of
      G. duodenalis in these animals. Multilocus genotyping analysis also indicated
      broad genetic diversity of assemblage B isolates in these bamboo rats.
      CONCLUSIONS: This is the first report of the infection and genetic variations of
      G. duodenalis in bamboo rats. These findings will provide basic data for
      implementing effective strategies to control giardiasis in bamboo rats.

PMID- 30236167
TI  - The effect of a youth mental health service model on access to secondary mental
      healthcare for young people aged 14-25 years.
AB  - : Aims and methodThe Norfolk Youth Service was created in 2012 in response to
      calls to redesign mental health services to better meet the needs of young
      people. The new service model transcends traditional boundaries by creating a
      single, 'youth friendly' service for young people aged 14-25 years. The aim of
      this study was to investigate the effect of the transition to this new model on
      patterns of referral, acceptance and service use. We analysed routinely collected
      data on young people aged 14-25 years referred for secondary mental healthcare in
      Norfolk before and after implementation of the youth mental health service. The
      number of referrals, their age and gender, proportion of referrals accepted and
      average number of service contacts per referral by age pre- and post
      implementation were compared. RESULTS: Referrals increased by 68% following
      implementation of the new service model, but the proportion of referrals accepted
      fell by 27 percentage points. Before implementation of the youth service, there
      was a clear discrepancy between the peak age of referral and the age of those
      seen by services. Following implementation, service contacts were more equitable
      across ages, with no marked discontinuity at age 18 years.Clinical
      implicationsOur findings suggest that the transformation of services may have
      succeeded in reducing the 'cliff edge' in access to mental health services at the
      transition to adulthood. However, the sharp rise in referrals and reduction in
      the proportion of referrals accepted highlights the importance of considering
      possible unintended consequences of new service models.Declaration of
      interestsNone.

PMID- 30236168
TI  - Success in learning similar-sounding words predicts vocabulary depth above and
      beyond vocabulary breadth.
AB  - In lexical development, the specificity of phonological representations is
      important. The ability to build phonologically specific lexical representations
      predicts the number of words a child knows (vocabulary breadth), but it is not
      clear if it also fosters how well words are known (vocabulary depth). Sixty-six
      children were studied in kindergarten (age 5;7) and first grade (age 6;8). The
      predictive value of the ability to learn phonologically similar new words,
      phoneme discrimination ability, and phonological awareness on vocabulary breadth
      and depth were assessed using hierarchical regression. Word learning explained
      unique variance in kindergarten and first-grade vocabulary depth, over the other
      phonological factors. It did not explain unique variance in vocabulary breadth.
      Furthermore, even after controlling for kindergarten vocabulary breadth,
      kindergarten word learning still explained unique variance in first-grade
      vocabulary depth. Skill in learning phonologically similar words appears to
      predict knowledge children have about what words mean.

PMID- 30236169
TI  - Identification of odors, faces, cities and naming of objects in patients with
      subjective cognitive decline, mild cognitive impairment and Alzheimer's disease:
      a longitudinal study.
AB  - : ABSTRACTObjective:Recent studies have tried to find a reliable way of
      predicting the development of Alzheimer's Disease (AD) among patients with mild
      cognitive impairment (MCI), often focusing on olfactory dysfunction or semantic
      memory. Our study aimed to validate these findings while also comparing the
      predictive accuracy of olfactory and semantic assessments for this purpose.
      METHOD: Six hundred fifty patients (median age 68, 58% females) including
      controls, SCD (subjective cognitive decline), non-amnestic MCI (naMCI), amnestic
      MCI (aMCI), and AD patients were tested for olfactory dysfunction by means of
      odor identification testing and semantic memory. Of those 650 patients, 120
      participants with SCD, naMCI, or aMCI at baseline underwent a follow-up
      examination after two years on average. Of these 120 patients, 12% had developed
      AD at follow-up (converters), while 88% did not develop AD at follow-up (non
      converters). RESULTS: Analysis showed a significant difference only for initial
      olfactory identification between converters and non-converters. Sensitivity of
      impairment of olfactory identification for AD prediction was low at 46.2%,
      although specificity was high at 81.9%. Semantic memory impairment at baseline
      was not significantly related to AD conversion, although, when naming objects,
      significant differences were found between AD patients and all other groups and
      between naMCI and aMCI patients compared to controls and SCD patients.
      CONCLUSIONS: Objective olfactory assessments are promising instruments for
      predicting the conversion to AD among MCI patients. However, due to their low
      sensitivity and high specificity, a combination with other neuropsychological
      tests might lead to an improved predictive accuracy. Further longitudinal studies
      with more participants are required to investigate the usefulness of semantic
      memory tests in this case.

PMID- 30236170
TI  - It is ethical to diagnose a public figure one has not personally examined.
AB  - SummaryShould psychiatrists be able to speculate in the press or social media
      about their theories? John Gartner argues the risk to warn the public of concerns
      about public figures overrides the duty of confidentiality; whereas Alex Langford
      suggests this is beyond the ethical remit of psychiatric practice.Declaration of
      interestA.O'B is joint debates and analysis Editor of the British Journal of
      Psychiatry. J.G. is the founder of Duty To Warn, an association of mental health
      professionals who advocate the president's removal under the 25th Amendment on
      the grounds that he is psychologically unfit and dangerous.

PMID- 30236171
TI  - PRMT1-dependent macrophage IL6 production is required for alcohol-induced HCC
      progression.
AB  - Alcohol is a well-established risk factor for hepatocellular carcinoma, but the
      mechanisms are not well understood. Several studies suggested that alcohol
      promotes tumor growth by altering immune cell phenotypesin the liver.Arginine
      methylation is a common posttranslational modification generated mostly by a
      single protein,PRMT1. In myeloid cells PRMT1 is a key regulator of immune
      response. Myeloid specific PRMT1 knockout mice are hyper-responsive to LPS and
      deficient in PPARgamma-dependent macrophage M2 polarization. We aimed to define
      the role of myeloid PRMT1 in alcohol-associated liver tumor progressionusing a
      mouse model of DEN injection followed by Lieber-DeCarli alcohol liquid diet
      feeding. We found that PRMT1 knockout mice showed significantly lower expression
      of IL10 and IL6 cytokines in the liverand downstream STAT3 activation, which
      correlated with reduced number of surface tumors, reduced proliferation and
      reduced number of M2 macrophages in the liver as well as within proliferating
      nodules. We found that blocking IL6 signaling in alcohol fed mice reducedthe
      number of tumorsand liver proliferation in wild type mice but not in knockout
      mice suggesting that reduced IL6 in PRMT1 knockout mice contributes to the
      protection from alcohol. Additionally, PRMT1 knockout did not show any protection
      in tumor formation in the absence of alcohol. Finally, we confirmed that this
      mechanism is relevant in humans. We found that PRMT1 expression in tumor
      associated macrophages correlated with STAT3 activation in human HCC specimens.
      Taken together these data suggest that the PRMT1-IL6-STAT3 axis is an important
      mechanism of alcohol-associated tumor progression.

PMID- 30236173
TI  - Abstracts of Scientific Presentations 2018 AALAS National Meeting Baltimore,
      Maryland.

PMID- 30236172
TI  - Elimination of Wnt secretion from stellate cells is dispensable for zonation and
      development of liver fibrosis following hepatobiliary injury.
AB  - Background: Alterations in the Wnt signaling pathway including those impacting
      hepatic stellate cells (HSC) have been implicated in liver fibrosis. Methods: In
      the current study, we first examined the expression of Wnt genes in human HSC
      (HHSC) after treatment with a pro-fibrogenic factor TGFbeta1. Next, we generated
      HSC-specific Wntless (Wls) knockout (KO) using the Lrat-cre and Wls-floxed mice.
      KO and littermate controls (CON) were characterized for any basal phenotype and
      subjected to two liver fibrosis protocols. Results: In vitro, TGFbeta1 induced
      expression of Wnt2, 5a and 9a while decreasing Wnt2b, 3a, 4 and 11 in HHSC. In
      vivo, KO and CON mice were born at normal Mendelian ratio and lacked any overt
      phenotype. Loss of Wnt secretion from HSC had no effect on liver weight and did
      not impact beta-catenin activation in the pericentral hepatocytes. After 7 days
      of bile duct ligation (BDL), KO and CON showed comparable levels of serum
      alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total
      and direct bilirubin. Comparable histology, Sirius red staining and
      immunohistochemistry for alpha-SMA, desmin, Ki67, F4/80 and CD45 indicated
      similar proliferation, inflammation and portal fibrosis in both groups. Biweekly
      administration of carbon tetrachloride for 4 or 8 weeks also led to comparable
      serum biochemistry, inflammation and fibrosis in KO and CON. Conclusion: Specific
      Wnt genes were altered in HHSC in response to TGFbeta1; however, eliminating Wnt
      secretion from HSC did not impact basal beta-catenin activation in normal liver,
      nor did it alter the injury-repair response during development of liver fibrosis.

PMID- 30236174
TI  - Curbing the tuberculosis and diabetes co-epidemic: strategies for the integration
      of clinical care and research.

PMID- 30236175
TI  - Closing the book on Category II: time for individualized regimens for patients
      with recurrent tuberculosis.

PMID- 30236176
TI  - 'Mind the gap': detecting the missing TB cases through active case finding.

PMID- 30236177
TI  - Diagnosis of tuberculosis among children: leave no stone unturned.

PMID- 30236178
TI  - How can integrated care and research assist in achieving the SDG targets for
      diabetes, tuberculosis and HIV/AIDS?
AB  - Integrating the management and care of communicable diseases, such as
      tuberculosis (TB) and human immunodeficiency virus/acquired immune-deficiency
      syndrome (HIV/AIDS), and non-communicable diseases, particularly diabetes
      mellitus (DM), may help to achieve the ambitious health-related targets of the
      Sustainable Development Goals (SDG 3.3 and 3.4) by 2030. There are five important
      reasons to integrate. First, we need to integrate to prevent disease. In sub
      Saharan Africa, in particular, HIV infection is the main driver of the TB
      epidemic, and antiretroviral therapy combined with isoniazid preventive therapy
      (IPT) can reduce TB case notification rates. In Asia, DM is another important
      driver of the TB epidemic, and preventing or controlling DM can reduce the risk
      of TB. Second, we need to integrate to diagnose cases. Between a third to a half
      of those living with HIV, TB or DM do not know they have the disease, and bi
      directional screening, whereby TB patients are screened for HIV and DM or people
      living with HIV and DM are screened for TB, can help to identify these 'missing
      cases'. Third, we need to integrate to better treat and manage patients who have
      a combination of two or more of these diseases, so that treatment success and
      retention on treatment can be optimised. Fourth, we should integrate to ensure
      better infection control practices for both TB and HIV infection in health
      facilities and congregate settings, such as prisons. Finally, we should integrate
      and learn how to monitor, record and report, particularly in relation to the
      cascade of events implicit in the HIV/AIDS and TB 90-90-90 targets.

PMID- 30236180
TI  - A systematic review of active case-finding strategies for tuberculosis in
      homeless populations.
AB  - SETTING: Tuberculosis (TB) is prevalent in the homeless population, and can
      create health inequalities and challenges for eradication. Evidence-based
      approaches to active case finding (ACF) are needed. OBJECTIVES: To determine the
      effectiveness of ACF for TB control, and identify strategies to improve uptake of
      screening and the diagnostic pathway in homeless populations in low- and medium
      burden settings. Secondary objectives were to assess the yield of screening and
      participant characteristics. DESIGN: A systematic search of electronic databases
      and grey literature sources identified ACF studies that reported population
      measures (prevalence or incidence) of TB control, and/or uptake and/or yield of
      screening for latent tuberculous infection (LTBI) or active TB affecting any
      site. Studies were described using narrative synthesis. RESULTS: Twenty studies
      met the inclusion criteria. Studies were heterogeneous across multiple elements,
      including programme design, which likely contributed to variability in outcomes.
      ACF was associated with reductions in TB rates in three time-trend analyses. The
      strongest evidence for improving uptake of screening was for incentives, with
      mixed evidence for peer educators. At the observational level, professional
      support and mandatory screening may also improve uptake, and additional community
      support enhanced completion of the diagnostic pathway. Those most likely to be
      diagnosed with TB appeared less likely to accept screening. Yield of screening
      was 1.5-57% (41 684 participants) for LTBI, and 0-3.1% (91 771 participants) for
      active TB. CONCLUSION: Observational evidence suggests that ACF is effective.
      Strategies to improve screening uptake were identified. Variability in uptake and
      yield necessitates programmes tailored to local populations; areas for further
      research were identified.

PMID- 30236179
TI  - A systematic review of clinical outcomes on the WHO Category II retreatment
      regimen for tuberculosis.
AB  - OBJECTIVE: To assess the clinical outcomes of patients prescribed the World
      Health Organization (WHO) Category II retreatment regimen for tuberculosis (TB).
      DESIGN: A systematic review of the literature was performed by searching
      Medscape, Embase and Scopus databases for cohort studies and clinical trials
      reporting outcomes in adult patients on the Category II retreatment regimen.
      RESULTS: The proportion of patients successfully completing the retreatment
      regimen varied from 27% to 92% in the 39 studies included in this review. In only
      2/39 (5%) studies was the treatment success rate > 85%. There are very few data
      concerning outcomes in patients categorised as 'other', and outcomes in this
      subgroup are variable. Of the five studies reporting disaggregated outcomes in
      human immunodeficiency virus (HIV) positive people, four demonstrated worse
      outcomes than in HIV-negative people on the retreatment regimen. Only four
      studies reported disaggregated outcomes in patients with isoniazid (INH)
      resistance, and treatment success rates varied from 11% to 78%. CONCLUSION:
      Clinical outcomes on the Category II retreatment regimen are poor across various
      populations. Improvements in management should consider the holistic treatment of
      comorbidity and comprehensive approaches to drug resistance in patients with
      recurrent TB, including a standardised approach for the management of INH
      resistance in patients who develop recurrent TB in settings without reliable
      access to comprehensive drug susceptibility testing.

PMID- 30236182
TI  - 'Something so hard': a mixed-methods study of home sputum collection for
      tuberculosis contact investigation in Uganda.
AB  - BACKGROUND: Home sputum collection could facilitate prompt evaluation and
      diagnosis of tuberculosis (TB) among contacts of patients with active TB. We
      analyzed barriers to home-based collection as part of an enhanced intervention
      for household TB contact investigation in Kampala, Uganda. DESIGN: We conducted a
      convergent mixed-methods study to describe the outcomes of home sputum collection
      in 91 contacts and examine their context through 19 nested contact interviews and
      two focus group discussions with lay health workers (LHWs). RESULTS: LHWs
      collected sputum from 35 (39%) contacts. Contacts reporting cough were more
      likely to provide sputum than those with other symptoms or risk factors (53% vs.
      15%, RR 3.6, 95%CI 1.5-2.8, P < 0.001). Males were more likely than females to
      provide sputum (54% vs. 32%, RR 1.7, 95%CI 1.0-2.8, P = 0.05). Contacts said
      support from the index patient and the convenience of the home visit facilitated
      collection. Missing containers and difficulty producing sputum spontaneously
      impeded collection. Women identified stigma as a barrier. LHWs emphasized
      difficulty in procuring sputum and discomfort pressing contacts to produce
      sputum. CONCLUSIONS: Home sputum collection by LHWs entails different challenges
      from sputum collection in clinical settings. More research is needed to develop
      interventions to mitigate stigma and increase success of home-based collection.

PMID- 30236181
TI  - Treatment outcome of tuberculosis patients detected using accelerated vs. passive
      case finding in Myanmar.
AB  - SETTING: Several projects involving accelerated or active case finding (ACF) of
      tuberculosis (TB) cases are being implemented in Myanmar. However, there is a
      concern that patients detected using ACF have poorer TB treatment outcomes than
      those detected using passive case finding (PCF). OBJECTIVE: To assess differences
      in the demographics, clinical profile and treatment outcomes of patients detected
      using ACF and PCF. DESIGN: Retrospective cohort study of TB patients diagnosed
      and enrolled for treatment during 2014-2016. RESULTS: Of 16 048 patients
      enrolled, 2226 (16%) were detected using ACF; the treatment success rate (cured
      and completed) was 88%. A higher proportion of cases detected using ACF were aged
      ?55 years, human immunodeficiency virus (HIV) negative and sputum smear-positive
      pulmonary TB. After adjusting for differences in demographic and clinical
      characteristics, we found that treatment outcomes in patients detected using ACF
      and PCF were not significantly different (adjusted relative risk [aRR] 0.89,
      95%CI 0.78-1.00). Male sex, age ? 55 years, patients with a previous history of
      TB and HIV positivity were independently associated with unsuccessful outcomes.
      CONCLUSION: ACF detected a significant proportion of TB cases in study townships;
      treatment outcomes in cases detected using ACF and those detected using PCF were
      similar. More tailored interventions are needed to improve treatment outcomes in
      patients at a higher risk of unsuccessful treatment outcomes.

PMID- 30236183
TI  - Latent tuberculous infection among foreign-born individuals applying to shelters
      in the metropolitan area of Milan.
AB  - SETTING: Screening for latent tuberculous infection (LTBI) of groups at high risk
      of active tuberculosis (TB) is a key component of the End TB Strategy. OBJECTIVE:
      To conduct a retrospective descriptive analysis of LTBI rates among foreign-born
      individuals applying to shelters in the metropolitan area of Milan, Italy.
      DESIGN: All foreign-born individuals registering for accommodation centres in the
      city of Milan from November 2009 to April 2017 were screened for active TB and
      LTBI. Individuals aged <36 years with a tuberculin skin test (TST) induration of
      >10 mm were offered confirmatory testing with QuantiFERON(r)-TB Gold In-Tube (QFT
      GIT). RESULTS: Of the 2666 TST-positive migrants aged <36 years who underwent
      LTBI confirmation testing, 1322 (49.6%) tested negative, 1339 (50.2%) were
      positive and five (0.2%) had indeterminate results. In the multivariate analysis,
      TB incidence in the country of origin and age were significantly associated with
      QFT-GIT positivity. Although estimated TB incidence in Eritrea, Morocco and
      Romania was ?100/100 000 person-years (py), the probability of being QFT-GIT
      positive in individuals from these countries were not statistically significantly
      different from individuals from countries with TB incidence > 250/100 000 person
      years. CONCLUSION: Our data showed a high proportion of LTBI among individuals
      coming from intermediate TB burden countries.

PMID- 30236184
TI  - Prevalence and screening of active tuberculosis in a prison in the South of
      Brazil.
AB  - SETTING: Tuberculosis (TB) remains a challenge in Brazil, particularly among
      prison inmates. OBJECTIVE: To assess TB prevalence by active case finding in a
      public prison in southern Brazil. DESIGN: Prison inmates were screened for TB
      using the presence of cough and chest X-ray (CXR) from October 2014 to August
      2016. Presence of cough, irrespective of duration, and abnormal CXRs were further
      investigated using laboratory tests. RESULTS: Of 10 326 inmates screened, 196 had
      confirmed TB (1898/100 000 inmates screened). At the first screening, 1759
      inmates presented with cough only, 16 of whom had TB; among those with only
      abnormal CXR (n = 1273), 92 had TB. Xpert was positive in 155 patients, and
      negative in 15; these results were confirmed using culture. The remaining 26
      patients did not undergo Xpert testing and were confirmed using microscopy (27%),
      culture (42%) or both (31%). CONCLUSION: The combined use of symptom screening
      (cough) and CXR was much more effective in maximising TB yield than using either
      method alone. If patients presenting with cough alone had not been investigated,
      10% of TB patients would have been missed; if those with abnormal CXR but no
      cough had not been investigated, 51% of TB patients would have been missed. We
      detected high TB prevalence in this prison by using active case finding.

PMID- 30236185
TI  - Contribution of the interferon-gamma release assay to tuberculosis diagnosis in
      children and adolescents.
AB  - SETTING: As conclusive data on the performance of interferon-gamma release assays
      (IGRAs) in paediatric TB are lacking, many guidelines do not recommend their use
      for TB diagnosis in this population in Brazil. OBJECTIVE: To evaluate the
      performance of an IGRA by investigating its concordance with the tuberculin skin
      test (TST) and the role of IGRAs in clinical management and treatment outcomes in
      children with TB. DESIGN: A historic cohort study was used to evaluate the
      performance of T-SPOT(r).TB (ELISpot) and other tests, such as the TST, in
      paediatric patients with or without immunodeficiency who were under investigation
      for latent tuberculous infection (LTBI) or active tuberculosis (TB). RESULTS: Of
      86 paediatric patients evaluated, 41 (48%) were immunocompetent and 45 (52%)
      immunocompromised. All patients underwent T-SPOT.TB, while 63 underwent both
      ELISpot and TST; test results were concordant in 50 patients (79.4%): 22/31 (71%)
      in immunocompetent (kappa = 0.418, P = 0.02) and 28/32 (87.5%) in
      immunocompromised patients (kappa = 0.526, P = 0.003). TB was diagnosed on the
      basis of the ELISpot result in 21% (18/86) cases; the contribution of the ELISpot
      assay was greater in immunocompetent patients than in those who were
      immunocompromised (13/41, 31.7% vs. 5/45, 11.1%, chi2 P = 0.038). CONCLUSION:
      ELISpot and TST results were moderately concordant in both groups of patients.
      ELISpot contribution was higher among immunocompetent patients than among
      immunocompromised patients.

PMID- 30236186
TI  - Barriers to screening and isoniazid preventive therapy for child contacts of
      tuberculosis patients.
AB  - BACKGROUND: India's guidelines recommend tuberculosis (TB) screening of household
      contacts aged <6 years and isoniazid preventive therapy (IPT) for children
      without active disease. We evaluated the current status and barriers to screening
      and IPT provision among the child contacts of TB patients. METHODS: Questionnaire
      and health record data were collected from index cases and health care providers
      (HCPs) at Sassoon General Hospital, Pune, India. RESULTS: Of 80 adult TB cases,
      24 (30%) reported that an HCP recommended TB screening of their child contacts;
      49/178 (28%) child contacts were screened. Sixteen (33%) children had active TB,
      and 28 (85%) of those who screened negative were prescribed IPT. Nineteen (76%)
      HCPs reported recommending child contact screening. Only 8 (32%) reported ever
      prescribing IPT. Lack of TB screening and IPT provision for child contacts was
      associated with inadequate HCP counseling (aOR 19.5, P < 0.001), a non-parent
      index case (aOR 3.72, P = 0.008) and lack of postgraduate HCP qualification (aOR
      19.12, P = 0.04). CONCLUSIONS: TB screening and IPT provision for child contacts
      of adults with TB were infrequent. Many screened children had active TB.
      Universal, timely TB screening and IPT for exposed children are urgently needed
      to reduce pediatric TB in India.

PMID- 30236187
TI  - Cost-effectiveness of home-based vs. in-hospital treatment of paediatric
      tuberculous meningitis.
AB  - SETTING: Cape Town, South Africa, 2014. OBJECTIVE: To assess the societal costs
      and cost-effectiveness of home-based vs. in-hospital treatment of paediatric
      tuberculous meningitis. DESIGN: This was an economic evaluation from a societal
      perspective using probabilistic analysis. Health care, informal care, lost
      productivity costs and costs in other sectors, health-related quality of life
      (HRQoL) and family impact were assessed during interviews with care givers,
      children, medical staff and management. RESULTS: Societal costs for home-based
      treatment were USD3857, and USD28 043 for in-hospital treatment. Home-based vs.
      in-hospital treatment HRQoL scores were 90.9% vs. 84.5%, while family impact
      scores were 94.8% vs. 73.1%. The point estimate of the incremental cost
      effectiveness ratio indicated that improving HRQoL and family impact by 1% was
      associated with a saving of respectively USD3726 and USD1140 for home-based vs.
      in-hospital treatment. The probability that home-based treatment was less
      expensive and more effective than in-hospital treatment was 96.3% for HRQoL and
      100% for family impact. CONCLUSION: Societal costs of home-based treatment were
      lower than for in-hospital treatment. Children treated at home had a better HRQoL
      and family impact scores. Home-based treatment was a cost-effective alternative
      to in-hospital treatment of drug-susceptible tuberculous meningitis.

PMID- 30236188
TI  - Quality of care in childhood tuberculosis diagnosis at primary care clinics in
      Kampala, Uganda.
AB  - OBJECTIVE: To assess the quality of routine childhood tuberculosis (TB)
      evaluation in Kampala, Uganda. SETTING AND DESIGN: This was a cross-sectional
      study of children aged <15 years attending six government-run clinics from
      November 2015 to December 2016. Clinicians completed a standardized patient
      record form for all child visits. We assessed the following performance
      indicators of TB evaluation developed based on the Desk Guide of the
      International Union Against Tuberculosis and Lung Disease, an evidence-based
      decision aid on childhood TB diagnosis and management for clinicians: proportion
      screened for TB symptoms or contact history, proportion referred for laboratory
      evaluation if screen-positive, and proportion treated for TB if test-positive or
      meeting clinical criteria. RESULTS: Of 24 566 consecutive children enrolled, 11
      614 (47%) were fully screened for TB symptoms. Of 1747 (15%) children who
      screened positive, 360 (21%) had sputum examined, including 159 (44%) using smear
      microscopy, 244 (67%) using Xpert(r) MTB/RIF, and 52 (14%) using both techniques.
      Treatment was initiated in 18/20 (80%) children who tested positive. An
      additional 65 screen-positive children met the clinical criteria for TB; none
      were initiated on treatment. CONCLUSIONS: Large gaps exist along the pathway to
      diagnosis and treatment of childhood TB. There is an urgent need for enhanced
      implementation of evidence-based approaches to TB diagnosis to improve outcomes
      in childhood TB.

PMID- 30236189
TI  - Prevalence and risk factors associated with tuberculosis disease in Suratthani
      Central Prison, Thailand.
AB  - SETTING: A prison in Suratthani Province, South Thailand. OBJECTIVES: To measure
      the prevalence of and identify the risk factors associated with tuberculosis (TB)
      disease among prison inmates. METHOD: This was a cross-sectional surveillance
      study. All prison inmates were screened for TB using a national TB screening
      questionnaire and chest X-ray (CXR) in July-December 2015. We collected sputum
      smear and Xpert(r) MTB/RIF results from prison inmates with a questionnaire score
      of ?3 points or CXR suggestive of TB. Case definitions were: 1) definite TB: TB
      confirmed using sputum smear microscopy or Xpert; 2) probable TB: CXR consistent
      with active TB, together with clinical and CXR improvement after treatment; 3) TB
      case: definite and probable cases. RESULTS: Of 4007 prison inmates, 84 were
      diagnosed with TB. TB prevalence was 2.1%: 61 (1.6%) were definite TB cases. TB
      was associated with human immunodeficiency virus (HIV) positivity (adjusted OR
      [aOR] 7.22, 95%CI 1.85-28.22, P = 0.004), pre-incarceration income <Thai baht 15
      000 (aOR 4.63, 95%CI 1.37-15.69, P = 0.014), overcrowding (aOR 3.73, 95%CI 1.08
      12.93, P = 0.038) and prolonged incarceration ?3 years (aOR 3.29, 95%CI 1.39
      7.82, P = 0.007). CONCLUSIONS: Prevalence of TB disease in Suratthani Central
      Prison was high. HIV infection, prolonged incarceration, overcrowding and low pre
      incarceration income were significant risk factors associated with TB.

PMID- 30236190
TI  - Prevalence of pulmonary tuberculosis among students in three eastern Ethiopian
      universities.
AB  - SETTINGS: Three universities located in eastern Ethiopia: Haramaya University,
      Haramaya; Dire-Dawa University, Dire-Dawa; and Jigjiga University, Jigjiga.
      OBJECTIVE: To determine the burden of pulmonary tuberculosis (PTB) among
      university students and to identify risk factors for the development of TB
      disease. DESIGN: All full-time university students were screened for symptoms of
      PTB and sputum was collected for acid-fast bacilli (AFB) examination and culture
      for Mycobacterium tuberculosis. RESULTS: Of 35 344 students screened, we
      identified 153 PTB cases that occurred over the 1-year study period, or 433/100
      000 students. Of these, 117 (76%) PTB cases were found through passive case
      finding at student health centres, while 36 (24%) previously undiagnosed patients
      were identified through active case finding. Sixteen cases detected using active
      case finding (44%) were smear-positive. Living in a dormitory with ?5 students
      and attending university for ?2 years were both significantly associated with PTB
      (adjusted OR 2.49 and 3.79, respectively, P < 0.001). In persons who underwent
      drug susceptibility testing, 11 (30.5%) had resistance to at least one first-line
      anti-tuberculosis drug. CONCLUSION: We found a high burden of TB among university
      students in eastern Ethiopia. Screening for PTB upon university admission and at
      regular intervals should be considered to minimise TB transmission on university
      campuses.

PMID- 30236191
TI  - HIV screening of tuberculosis patients in Portugal: what are we missing?
AB  - BACKGROUND: Knowledge of human immunodeficiency virus (HIV) status is essential
      to effectively manage both tuberculosis (TB) and HIV infection. This is why the
      World Health Organization (WHO) recommends routine HIV testing in all TB
      patients. OBJECTIVE: To determine the number of TB patients with unknown HIV
      status in Portugal and to identify the factors associated with unknown HIV
      status. METHODS: A retrospective study of all TB notifications from 2008 to 2014
      in Portugal was conducted. A multiple logistic regression model was used to
      evaluate the association of sociodemographic and clinical factors with unknown
      HIV status. RESULTS: We examined the records of 18 445 patients with TB
      notification, 2402 of whom (13%) had unknown HIV status. Unknown HIV status was
      positively associated with age ?65 years (adjusted odds ratio [aOR] 1.208, 95%CI
      1.037-1.408) and extra-pulmonary TB (aOR 1.381, 95%CI 1.252-1.523), but
      negatively associated with unemployment (aOR 0.755, 95%CI 0.637-0.895), alcohol
      dependence (aOR 0.809, 95%CI 0.682-0.959) and drug dependence (aOR 0.566, 95%CI
      0.449-0.713). CONCLUSION: Risk perception is the most important barrier to
      complete knowledge of HIV status in TB patients in Portugal. Given the importance
      of HIV screening in TB patients, every effort should be made to ensure that all
      TB patients undergo HIV screening.

PMID- 30236192
TI  - Programmatic management of patients with pre-extensively drug-resistant
      tuberculosis in Peru, 2011-2014.
AB  - BACKGROUND: In Peru, a treatment approach for extensively drug-resistant
      tuberculosis (XDR-TB) incorporating World Health Organization Group 5 drugs and
      patient-centred care has achieved 65% success. To extend this approach to pre-XDR
      TB patients, we evaluated this population separately. OBJECTIVE: To assess
      programmatic management of pre-XDR-TB. METHOD: Retrospective study using the
      official national registry from 2011 to 2014. Cases were separately evaluated
      according to resistance to fluoroquinolones (FQs) (pre-XDR-F) or to second-line
      injectables (SLIs) (pre-XDR-I). RESULTS: Of 610 pre-XDR-TB patients, 120 (20%)
      had pre-XDR-F and 490 (80%) had pre-XDR-I. Pre-XDR-F cases were older (34 years
      vs. 28 years, P < 0.001) and a higher proportion had previously received two or
      more regimens (70% vs. 38%, P < 0.001). Among the 452 patients who started
      treatment in 2011-2013, treatment success was 43.3%, 26.5% were lost to follow
      up, 12.1% died and 13.7% failed treatment. Success was higher in pre-XDR-I
      (48.5%) than pre-XDR-F (21.4%) patients. History of previous treatment (OR 2.23,
      95%CI 1.52-3.38) and pre-XDR-F (OR 2.39, CI 1.18-4.83) were associated with
      unsuccessful outcomes. CONCLUSION: Programmatic management of pre-XDR-TB has not
      been successful, particularly in pre-XDR-F patients, with lower rates of success
      than those achieved in the same setting for XDR-TB. The strategy used for XDR-TB
      should be extended to pre-XDR-TB patients in Peru.

PMID- 30236193
TI  - High IL-6 and VEGF-A levels correlate with delayed wound healing in cervical
      lymph node tuberculosis patients.
AB  - SETTING: A high proportion of tuberculosis (TB) patients experience delayed wound
      healing after surgery, and the specific reasons for this phenomenon are not yet
      clear. OBJECTIVE: To analyse cytokine and growth factors at surgical sites to
      determine their contribution to delayed wound healing in patients with cervical
      lymph node TB (CLNT). DESIGN: We measured levels of interleukin (IL) 1beta, IL-6,
      IL-10, IL-22, epidermal growth factor, fibroblast growth factor-2, interferon
      gamma, tumour necrosis factor alpha and vascular endothelial growth factor A
      (VEGF-A) in cervical wound drainage fluid from 36 CLNT patients who underwent
      lymphadenectomy and in 24 thyroidectomy patients. RESULTS: Wound drainage fluid
      from CLNT patients showed higher IL-6 (P = 0.007) and VEGF-A (P < 0.001) levels
      than control thyroidectomy patients (P < 0.05). CLNT patients with a delayed
      healing time (>5 days; n = 18) showed higher IL-6 (P = 0.002) and VEGF-A (P <
      0.001) levels in wound drainage fluid than CLNT patients with normal healing
      times (?5 days; n = 18). IL-6 (OR 11.280, 95%CI 1.413-90.028; P = 0.022) and VEGF
      A (OR 13.510, 95%CI 2.168-84.182; P = 0.005) can independently and significantly
      predict wound healing time in CLNT patients. CONCLUSION: These findings
      demonstrate that high IL-6 and VEGF-A levels in the post-operative wound fluid of
      CLNT patients correlate with delayed wound healing.

PMID- 30236194
TI  - Prediction equations for spirometry in healthy children from Djibouti.
AB  - OBJECTIVE: To determine normal spirometric values in Djiboutian children and to
      compare these data with values reported by African studies and by the 2012 Global
      Lung Function Initiative. METHODS: Spirometric data from healthy Djiboutian
      children were collected and reference equations derived using the least mean
      squared method, which includes modelling skewness (lambda, L), mean (MU, M) and
      coefficient of variation (sigma, S) according to sex, age and height. In
      addition, the age-dependent lower limits of normal were calculated. RESULTS:
      Spirometric values in Djiboutian children were lower than those obtained for
      other Black children; these differences were relatively small and clinically
      irrelevant, representing differences of approximately 3% predicted. However,
      significant differences were observed between our equations and those for
      Tunisian children. CONCLUSION: The results of the present study could help to
      improve the clinical diagnosis of respiratory diseases in Djiboutian children.

PMID- 30236195
TI  - A case of laboratory cross-contamination of Mycobacterium tuberculosis identified
      using comparative genomics.
AB  - BACKGROUND: Two false-positive tuberculosis (TB) cases in Yamagata Prefecture,
      Japan, 2016. OBJECTIVE: To report the effectiveness of comparative genomics of
      Mycobacterium tuberculosis for identification of cross-contamination cases.
      DESIGN: Case report of laboratory cross-contamination. RESULTS: Beginning with
      detection of an identical genotype in two M. tuberculosis strains using variable
      number of tandem repeat typing, we suspected M. tuberculosis cross-contamination
      of specimens collected in a mycobacteriology laboratory based on epidemiological
      investigations. This suspicion was confirmed using comparative genomics of the
      two M. tuberculosis strains and a strain from an epidemiologically unrelated
      specimen from the same batch as the two strains in the mycobacteriology
      laboratory. All strains had an identical genomic sequence with no single
      nucleotide variants. CONCLUSION: Comparative genomics, which offers the highest
      discrimination power, is a potent tool for identifying laboratory cross
      contamination using epidemiological investigations.

PMID- 30236196
TI  - Severe rifamycin-induced immune thrombocytopenia in a patient with extra
      pulmonary tuberculosis.

PMID- 30236197
TI  - ERRATA.

PMID- 30236198
TI  - [NSD3 suppresses LPS-triggered TNF-alpha production via promoting the
      dimethylation of histone H3K36 in macrophages].
AB  - Objective To investigate the role of nuclear receptor-binding SET domain protein
      3 (NSD3) in lipopolysaccharide (LPS)-triggered tumor necrosis factor alpha (TNF
      alpha) production in macrophages and the underlying epigenetic mechanism. Methods
      The experiment used murine peritoneal macrophages and RAW264.7 cells as cell
      models. The mRNA and protein level of NSD3 were detected by real-time
      quantitative PCR and Western blot analysis in mouse peritoneal macrophages
      stimulated with LPS (100 ng/mL). ELISA was used to detect the production of TNF
      alpha in NSD3-overexpressing RAW264.7 cells or NSD3-silencing peritoneal
      macrophages. Western blot analysis was performed to test the activation of LPS
      triggered NF-kappaBp65 in NSD3-silencing macrophages. Luciferase assay was used
      to assess NF-kappaBp65-mediated transcriptional activation of TNF-alpha gene.
      ChIP assay was used to detect the recruitment of H3K36 methylation to TNF-alpha
      gene promoter. Results LPS inhibited the expression of NSD3 in the macrophages.
      Over-expression of NSD3 suppressed LPS-triggered TNF-alpha production, and
      silencing NSD3 promoted LPS-triggered TNF-alpha production. However, NSD3 had no
      effect on the activation of LPS-triggered NF-kappaBp65. NSD3 enhanced NF
      kappaBp65-mediated transcriptional activation of TNF-alpha gene. NSD3 enhanced
      the dimethylation of H3K36 of TNF-alpha gene promoter. Conclusion NSD3 can
      promote the dimethylation of H3K36 of TNF-alpha gene promoter and suppress TNF
      alpha transcription and production.

PMID- 30236199
TI  - [MOMP of Legionella inhibits phagocytosis of RAW264.7 macrophages and enhances
      their chemotaxis by activating NOD2/RIP2 signaling pathway].
AB  - Objective To investigate the effect of the main outer membrane protein (MOMP) of
      Legionella on the phagocytosis and chemotaxis of RAW264.7 macrophages and explore
      its mechanism. Methods MOMP and RAW264.7 macrophages were cultured in vitro. The
      toxicity of MOMP to RAW264.7 macrophages was detected by CCK-8 assay and 50%
      inhibitory concentration (IC50) was determined. The RAW264.7 macrophages were
      treated by MOMP (1.14, 0.57, 0.28) MUg/mL and the control group was established.
      The cells and cultivate supernatants were collected 24, 48 and 72 hours after the
      RAW264.7 macrophages were treated by MOMP. The phagocytic function of macrophages
      was detected by the neutral red phagocytosis experiment; the chemotaxis function
      of macrophage was examined by TranswellTM assay, and the levels of monocyte
      chemoattractant protein 1 (MCP-1) and interleukin 10 (IL-10) in cell culture
      supernatant monocytes were detected by ELISA. Real-time quantitative PCR was used
      to check the mRNA level of macrophage nucleotide-binding oligomerization domain 1
      (NOD1), NOD2 and receptor-interacting protein 2 (RIP2). The protein levels of
      NOD1, NOD2 and RIP2 were detected by Western blot analysis. Results The IC50 of
      MOMP on RAW264.7 macrophages was 5.69 MUg/mL. Compared with the control cells,
      MOMP treatment caused a decrease of RAW264.7 macrophage phagocytosis in a dose-
      and time-dependent manner. With the increase of MOMP dosage, the chemotaxis of
      macrophages and the secretory levels of MCP-1 and IL-10 in the cell culture
      supernatant increased, and peaked in 36 hours. The mRNA and protein expression
      levels of NOD2, RIP2 also increased, mRNA levels of NOD2 and RIP2 peaked in 12
      hours, and protein levels peaked in 24 hours. Conclusion MOMP can inhibit the
      phagocytosis of RAW264.7 macrophages and enhance its chemotaxis function, which
      is related to the activation of NOD2/RIP2 signaling pathway.

PMID- 30236200
TI  - [Comparison of immunofluorescence cytochemical staining results in frozen
      sections of different-thickness neurospheres].
AB  - Objective To explore the optimal frozen section thickness of neurospheres for
      immunofluorescence cytochemical staining. Methods We selected the neurospheres of
      10-12-day suspension culture to make frozen sections of varying thickness: 4, 7
      and 10 MUm, and then performed immunofluorescent staining to compare the
      expression and location of nestin. Results The diameters of the neurospheres
      cultured for 10-12 days were among 200-250 MUm. The neurospheres were in a good
      condition and had a strong refractivity. The cells were spherical in shape, with
      burrs in the peripheral area. Practically, it was hard to make the 4 MUm frozen
      sections which were wrapped around themselves easily. The advantages were that,
      their cells had a clear-cut structure, uniform staining and practical density,
      thus making it easier to calculate the cell number. The imaging was clear and the
      nuclei were distinct, too. It could be seen that much of the whole cytoplasm,
      with the nestins presenting positive staining, wrapped itself around the nuclei
      in which the DAPI also presented positive staining, and intercellular details
      could be observed meanwhile. Comparatively, the 7 MUm frozen sections were not
      that hard to get. They were quite smooth and showed rather uniform staining. The
      cell number turned out to be larger than that of the 4 MUm frozen sections, but
      the cell structure was not that clear-cut, so it was difficult to make an
      accurate estimate of the cell number. Besides, to be in full focus could not be
      achieved while using fluorescent photography. Hence, only part of the entire cell
      morphology could be seen. The frozen slice of 10 MUm is relatively easy to make,
      the slice is flat, but did not have a clear-cut cell structure, either. There was
      a serious piling phenomenon and no clear imaging. Consequently, it was hard to
      see the complete cell morphology. Conclusion The 4 MUm frozen sections of
      neurospheres are more conducive to the observation and analysis of
      immunofluorescent staining results than those of other thicknesses.

PMID- 30236201
TI  - [4i, a novel PPARgamma ligand, inhibits the production of inflammatory cytokines
      in murine macrophages by blocking NF-kappaB and MAPK pathway].
AB  - Objective To investigate the anti-inflammatory activity and mechanism of
      peroxisome proliferator activated receptor gamma (PPARgamma) ligand 4i. Methods
      Mouse macrophages RAW264.7 at the logarithmic phase were induced by 100 ng/mL
      lipopolysaccharide (LPS). The effect of 4i (10 MUmol/L) on the production of
      tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) was investigated
      by ELISA. The effect of 4i on the protein levels of nuclear factor kappaB (NF
      kappaBp65), IkappaBalpha, JNK, ERK1/2, p38MAPK were detected by Western blot
      analysis. Furthermore, the role of PPARgamma in the regulation of inflammatory
      related NF-kappaB and MAPK signaling pathways was analyzed using GW9662 (5
      MUmol/L) which was a highly irreversible PPARgamma antagonist. And the docking
      analysis was carried out using SYBYL 8.1 software to investigate the binding
      interaction of 4i with PPARgamma ligand. Results The 4i significantly decreased
      the production of TNF-alpha and IL-6 in a time-dependent manner. It also
      inhibited the phosphorylation of NF-kappaBp65, IkappaBalpha, JNK, ERK1/2 and
      p38MAPK in varying degrees, and the suppressive effect of 4i could be reversed by
      GW9662. The 4i exhibited a strong binding ability with PPARgamma. Conclusion The
      anti-inflammation effect of 4i was due to the interaction with PPARgamma, thereby
      suppressing the activation of NF-kappaB and MAPK cascades and resulting in the
      decreased levels of TNF-alpha and IL-6.

PMID- 30236202
TI  - [Inhibitory effect of Fasudil on activation and inflammatory response of mouse
      astrocytes induced by lipopolysaccharide and its mechanism].
AB  - Objective To evaluate the influence of Fasudil on the lipopolysaccharide (LPS)
      induced activation and inflammatory response of astrocytes and TLR4/ NF-kappaB
      signaling pathway. Methods Astrocytes were separated from the cerebral cortex of
      newly-born C57BL/6 mice and cultured in vitro. The cells were divided into PBS
      control group, 1 MUg/mL LPS stimulation group, 1 MUg/mL LPS combined with 15
      MUg/mL Fasudil treatment group. The production of NO in the cell supernatant was
      detected by Griess reagent. The levels of tumor necrosis factor-alpha (TNF
      alpha), interleukin -6(IL-6), IL-10 and IL-4 were measured by ELISA. The
      expressions of glial fibrillary acidic protein (GFAP) and TLR4 in the astrocytes
      were detected by immunofluorescence cytochemistry. The protein levels of GFAP,
      TLR4 and p-NF-kappaBp65 were assessed by Western blot analysis. Results Compared
      with the PBS control group, the levels of NO, TNF-alpha and IL-6 in the LPS group
      significantly increased, but the levels of IL-10 and IL-4 decreased. Fasudil
      treatment significantly inhibited LPS-induced the secretion of NO, TNF-alpha and
      IL-6 and enhanced the production of IL-10 and IL-4. The expression of GFAP
      significantly decreased in the Fasudil treatment group, and the protein levels of
      TLR4 and p-NF-kappaBp65 also decreased. Conclusion Fasudil can inhibit LPS
      induced astrocyte activation and inflammatory response by blocking TLR4/NF-kappaB
      signaling pathway.

PMID- 30236203
TI  - [Antiviral effects of IL-27 on HBV in HepG2.2.15 cells via inducing MxA by STAT1
      signal transduction pathway].
AB  - Objective To investigate the effect of interleukin 27 (IL-27) on hepatitis B
      virus (HBV) replication and antigen secretion in HepG2.2.15 cells and related
      mechanisms. Methods HepG2.2.15 cells were treated with IL-27 at various doses.
      The levels of HBsAg and HBeAg in the supernatant of the cell cultures were
      measured by ELISA, and the levels of HBV DNA was detected by real-time
      quantitative PCR. The expression and localization of HBV core antigen (HBcAg) in
      HepG2.2.15 cells were observed by immunocytochemical staining. Moreover, the
      expression of STAT1, phosphorylated STAT1 (p-STAT1) and myxovirus-resistance
      protein A (MxA) were analyzed by Western blotting. Results After the treatment
      with different doses of IL-27, the levels of HBV-DNA, HBsAg, HBeAg and
      intracellular HBcAg in HepG2.2.15 cells gradually decreased. With the increase of
      IL-27 dose, the expression level of p-STAT1 significantly increased. There was no
      significant change in STAT1 expression. Further studies also showed that IL-27
      induced MxA expression in a dose- and time-dependent manner in HepG2.2.15 cells.
      Conclusion IL-27 could induces MxA expression by activating STAT signaling
      pathway to exert anti-HBV activity.

PMID- 30236204
TI  - [Caspase-9 (-Ex5+32 G/A) gene polymorphism is associated with caspase-9
      expression in degenerative nucleus pulposus of lumbar intervertebral disc].
AB  - Objective To investigate the relationship between caspase-9 (-Ex5+32 G/A) gene
      polymorphisms, Schneiderman score of magnetic resonance imaging (MRI) in lumbar
      disc degeneration and the expression of caspase-9 in degenerative nucleus
      pulposus. Methods The peripheral venous blood and prominent nucleus pulposus were
      obtained from 105 patients with lumbar disc herniation. Genomic DNA was extracted
      and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS). The caspase-9(-Ex5+32 G/A) gene polymorphisms were
      analyzed in all DNA samples. The expression of caspase-9 in the tissues was
      detected by immunohistochemical SP staining. The t test was used to analyze the
      difference between the genotypes and the expression of caspase-9 in
      intervertebral disc nucleus. Pearson correlation analysis was performed to assess
      the association between caspase-9 expression in nucleus pulposus and the MRI
      score of lumbar disc. Results MRI analysis showed that the patients with AA
      genotype had the highest MRI scores, but there were no significant differences in
      MRI scores among patients with AA, GA, and GG genotypes. Compared with GG
      genotype carriers, AA genotype carriers had a statistically significant
      difference in the expression of caspase-9 in nucleus pulposus. There was no
      correlation between the MRI score of lumbar disc degeneration and the expression
      of caspase-9 in the degenerated nucleus pulposus. Conclusion The caspase-9(
      Ex5+32 G/A) gene polymorphism is associated with the expression of caspase-9 in
      the degenerative nucleus pulposus. However, the MRI Schneiderman score is not
      significantly correlated with the expression of caspase-9 in degenerative nucleus
      pulposus.

PMID- 30236205
TI  - [miR-98-5p promotes apoptosis and inhibits migration by reducing the level of
      STAT3 in A549 cells].
AB  - Objective To explore the effects of microRNA-98-5p (miR-98-5p) on the growth of
      lung cancer A549 cells and its mechanism. Methods The expression of miR-98-5p in
      the normal human bronchial epithelial (HBE) cell line and NSCLC cell lines (A549,
      H1299 and H460) was detected using real-time quantitative PCR. The effects of miR
      98-5p mimic and miR-98-5p inhibitor (anti-miR-98-5p) on A549 cell proliferation
      were detected with CCK-8 assay. The influence of miR-98-5p on the apoptosis of
      A549 cells was tested by flow cytometry. The activities of caspase-3 and caspase
      9 were determined by commercial kits. The effects of miR-98-5p on the invasion
      and migration of A549 cells were detected with TranswellTM assay. The effects of
      miR-98-5p on the expression of STAT3 in A549 cells were verified using real-time
      quantitative PCR and Western blot analysis. Results Compared with HBE cells, the
      expression of miR-98-5p in A549, H1299, and H460 cells decreased markedly. The
      miR-98-5p mimic reduced cell proliferation, promoted cell apoptosis, and
      inhibited the migration of A549 cells. Meanwhile, miR-98-5p mimic significantly
      reduced the expression of STAT3 in A549 cells. Conclusion The miR-98-5p promotes
      apoptosis, inhibits migration of A549 cells by down-regulating STAT3 expression.

PMID- 30236206
TI  - [Expression and significance of WFDC2 in ovarian cancer based on multiple gene
      databases].
AB  - Objective To investigate the expression and clinical significance of whey acidic
      protein (WAP) 4-disulfide core domain 2 (WFDC2) in ovarian cancer. Methods The
      expression of WFDC2 gene in normal human tissues, ovarian cancer tissues and
      ovarian cancer cell lines and the correlation with the prognosis survival in
      patients with ovarian cancer were analyzed using the BioGPS database, Oncomine
      database, Cancer Cell Encyclopedia (CCLE) and Kaplan-Meier Plotter databases.
      Results BioGPS database analysis showed that the expression of WFDC2 was not
      found in normal ovarian tissues. Four hundred and seventeen samples were searched
      from Oncomine database, and the different expression of WFDC2 in 34 studies were
      statistically significant, which included the WFDC2 expression increasing in 19
      studies, and WFDC2 expression decreasing in 15 studies. Meta-analysis of 7
      studies meeting the setting conditions showed that the expression level of WFDC2
      was high in ovarian cancer tissues. CCLE analysis showed that the expression
      level of WFDC2 was also high in ovarian cancer cell lines; Kaplan-Meier Plotter
      database results showed the overall survival time of patients with ovarian cancer
      in the high WFDC2 expression group was significantly longer than that in the low
      WFDC2 expression group. Conclusion The expression of WFDC2 in ovarian cancer
      tissues is high, and which is significantly associated with the prognosis
      survival in patients with ovarian cancer.

PMID- 30236207
TI  - [Expression, purification and binding activity analysis of von Hippel-Lindau
      (VHL)].
AB  - Objective To purify recombinant protein of human von Hippel-Lindau (VHL) and
      identify its function. Methods VHL gene sequence was amplified from human mammary
      cDNA using PCR and inserted into the prokaryotic expression vector pGEX-KG.
      Glutathione S-transferase-VHL (GST-VHL) recombinant plasmid we obtained was
      converted into BL21(DE3) sensitive bacteria to induce a small amount of GST-VHL
      protein. The expressed product was detected by SDS-PAGE and Western blot
      analysis. The recombinant protein was purified by GST beads and its function was
      verified by GST pull-down assay. Results The obtained recombinant plasmid could
      be successfully digested by double enzymes. Gene sequencing showed that the VHL
      sequence was correct and there was no mutation. The recombinant protein with
      approximately relative molecular mass (Mr) 56 000 was purified by converting
      recombinant plasmid to BL21(DE3) sensitive bacteria and inducing it in small
      quantities. GST pull-down assay verified that GST-VHL recombinant protein had the
      function of binding hypoxia inducible factor-1 alpha (HIF-1 alpha) in vitro.
      Conclusion GST-VHL recombinant protein is purified and can combine with HIF
      1alpha protein in vitro.

PMID- 30236208
TI  - [Elevated level of serum PCSK9 in patients with systemic lupus erythematosus].
AB  - Objective To detect the level of serum proprotein convertase subtilisin/kexin
      type 9 (PCSK9) in patients with systemic lupus erythematosus (SLE) and
      investigate the correlation between PCSK9 level and disease parameters. Methods
      Forty-seven SLE patients and 30 age, sex-matched healthy controls (HCs) were
      included in our research. Traditional cardiovascular disease (CVD) risk factors
      were compared between the two groups. The level of serum PCSK9 was examined by
      ELISA. Carotid intima-media thickness (cIMT) was measured by carotid ultrasound.
      According to the measured value of cIMT, SLE patients were divided into SLE-AS
      (cIMT>=1.0 mm) and SLE-NonAS (cIMT<1.0 mm) subgroups. Atherogenic factors and
      PCSK9 levels were compared between the two subgroups. Univariate correlational
      analysis of PCSK9 levels and disease parameters was conducted in the SLE
      patients. Results No difference was found in the total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C), ApoA1, ApoB, triglyceride (TG), high
      density lipoprotein cholesterol (HDL-C), fasting blood-glucose (FBG), body mass
      index (BMI) or uric acid (UA) between the SLE patients and HCs. However, the
      higher ratio of cIMT thickening and the elevation of serum PCSK9 levels were
      observed in the SLE patients as compared with the HCs. No significant difference
      in the traditional risk factors for CVD was found, but significant difference in
      the level of C-reactive protein (CRP) existed between the SLE-AS subgroup and SLE
      NonAS subgroup. The level of serum PCSK9 in the SLE-AS subgroup was significantly
      higher than that in the SLE-NonAS subgroup. PCSK9 concentrations were positively
      correlated with CRP levels, but not correlated obviously with the age, SLEDAI,
      lipids parameters (TC, LDL-C, ApoA1, ApoB, TG, HDL-C), BMI or UA levels. This
      tendency seemed to be more significant in the female patients. Conclusion
      Elevated level of serum PCSK9 can be observed in SLE patients, especially in
      those with thickening of cIMT. PCSK9 may be associated with atherogenic
      inflammation in SLE.

PMID- 30236209
TI  - [Correlation analysis between the numbers of G-MDSCs and M-MDSCs in peripheral
      blood decrease and therapeutic effect in patients with colorectal cancer].
AB  - Objective To detect the frequencies of myeloid-derived suppressor cells (MDSCs)
      in the peripheral blood of patients with colorectal cancer (CRC) in an attempt to
      investigate the relationship between the change of MDSC frequencies and
      clinicopathologic characteristics of CRC patients. Methods The frequencies of
      granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs) in the peripheral
      blood of 82 CRC patients and 30 healthy volunteers were detected by flow
      cytometry. ANOVA and t-test were used to explore the relationship between the
      frequencies of MDSCs in the peripheral blood and the TNM stages, lymph node
      metastasis, tumor sites, histological grade as well as common therapeutic
      measures of CRC patients. Correlation analysis was performed to evaluate the
      correlation between the frequencies of G-MDSCs and M-MDSCs. Results Compared with
      the 30 healthy volunteers, the frequencies of G-MDSCs and M-MDSCs in the
      peripheral blood of the 82 CRC patients were statistically higher. The
      frequencies of G-MDSCs and M-MDSCs in the peripheral blood from TNF stage III and
      IV CRC patients were obviously higher than those from stage I and II patients,
      and CRC patients with lymph node metastasis had remarkably higher frequencies of
      G-MDSCs and M-MDSCs than the patients without lymph node metastasis. There were
      no statistical differences in the frequencies of G-MDSCs and M-MDSCs in the
      peripheral blood between CRC patients with different tumor sites as well as
      histological grades. Radical resection and effective adjuvant chemotherapy
      significantly decreased the frequencies of G-MDSCs and M-MDSCs in the peripheral
      blood of CRC patients. No statistical correlation was found between the
      frequencies of circulating G-MDSCs and M-MDSCs in CRC patients. Conclusion G-MDSC
      and M-MDSC frequencies in the peripheral blood of CRC patients significantly
      increased, and were closely associated with TNM stages and lymph node metastasis.
      Radical resection and effective adjuvant chemotherapy significantly reduced the
      frequencies of circulating G-MDSCs sand M-MDSCs of CRC patients.

PMID- 30236210
TI  - [Preparation of multivalent egg yolk IgY antibodies against Helicobacter pylori].
AB  - Objective To prepare a specific multivalent immunoglobulin of yolk (IgY) against
      multi-virulence factors of Helicobacter pylori (Hp). Methods The purified
      recombinant BabA2, UerB and FlaA of Hp were mixed equally with adjuvant, and then
      used to immunize egg-laying hens to produce specific multivalent IgY. Next, the
      biological characteristics of purified IgY were analyzed by SDS-PAGE, Western
      blot and ELISA. To analyze the inhibition effects of multivalent IgY on the
      growth of Hp in vitro, Hp was co-cultured with different final concentration of
      IgY (1, 5, 10) mg/mL in the presence or absence of antibiotics. Results After
      immunization, the titer of egg yolk IgY reached up to 1:150 000. Furthermore, the
      bacteriostasis assay showed that the multivalent IgY had a significant inhibitory
      effect on the growth of Hp at 5 mg/mL, and the combination with amoxicillin could
      further inhibited the growth of Hp. Conclusion The specific multivalent IgY
      against Hp is successfully prepared.

PMID- 30236211
TI  - Sociodemographic characteristics and clinical description of congenital syphilis
      patients and their mothers in Japan: a qualitative study, 2016.
AB  - Background: In Japan, congenital syphilis (CS) notifications have increased
      recently. However, little is known about the CS cases or the clinical and
      sociodemographic characteristics of the patients' mothers. Methods: Twelve cases
      of CS were reported through national surveillance in the period March-December
      2016, and the mothers of seven patients were included in this study. The
      patients' mothers and physicians completed a self-administered questionnaire,
      providing sociodemographic and clinical information of the patients and their
      mothers. In addition, we explored the awareness and knowledge of, attitudes
      towards and practices regarding CS occurrence through semistructured interviews
      with the mothers. Results: Of the seven CS patients, three were asymptomatic,
      with a range of non-specific clinical manifestations in the rest. The mothers
      tended to be of young age, unmarried and to have a history of commercial sex
      work, other sexually transmissible infections (STIs) and no or irregular prenatal
      care visits during pregnancy. Of the four mothers who had had regular prenatal
      care visits, two had tested negative for syphilis at the first trimester
      antenatal screening. Themes emerged that indicated challenges in preventing CS,
      including a lack of guidance or guidelines for physicians to consider testing for
      syphilis after the first trimester, lack of physicians' awareness or experience
      of syphilis or CS and a lack of awareness or knowledge in pregnant women
      regarding STIs. Conclusions: Key characteristics of recent CS patients and their
      mothers in Japan were revealed, identifying previously reported factors as well
      as new challenges. A holistic approach, designed to address challenges at the
      level of the healthcare system, healthcare provider and the pregnant woman and
      her partner will be important in preventing CS.

PMID- 30236212
TI  - Incidence and predictors of HIV, chlamydia and gonorrhoea among men who have sex
      with men attending a peer-based clinic.
AB  - Introduction: Despite a range of interventions, annual numbers of new diagnoses
      of HIV infection among men who have sex with men (MSM) in Australia have not
      declined in recent years. Peer-based sexual health clinics targeting MSM, such as
      the M Clinic in Perth (WA, Australia), have been put in place to provide safe sex
      counselling and to increase testing rates among MSM and who are at high risk of
      HIV infection. The aim of this study was to assess the incidence of HIV,
      chlamydia and gonorrhoea among men attending the M Clinic. Methods: This was a
      historical cohort study of repeated M Clinic clients from January 2011 to June
      2015 inclusive. Testing and risk factor data from M Clinic client software were
      used to estimate the incidence of HIV, chlamydia and gonorrhoea and associated
      factors. Results: The incidence of HIV, chlamydia and gonorrhoea was 1.87, 13.58
      and 6.48 per 100 person-years respectively. Older men had a higher incidence of
      HIV infection but a lower incidence of chlamydia and gonorrhoea than younger men.
      Conclusions: The HIV incidence was higher than found in similar studies in other
      Australian sexual health clinics, but the incidence of chlamydia and gonorrhoea
      was similar. The high HIV incidence among clients of the M Clinic points to the
      importance of making pre-exposure HIV prophylaxis available to clients of the M
      Clinic and similar services.

PMID- 30236214
TI  - Difficult Removal of a Central Venous Port Catheter.

PMID- 30236213
TI  - The Burden of Cancer in Germany.

PMID- 30236215
TI  - Cancers Due to Smoking and High Alcohol Consumption.
AB  - BACKGROUND: Tobacco and alcohol consumption are known causes of cancer. We set
      out to estimate the absolute numbers and proportions of cancer attributable to
      smoking and high alcohol consumption in Germany in 2018. METHODS: Numbers and
      proportions (population-attributable fractions, PAF) were calculated by sex and
      age group for ages 35 to 84 years based on population projections, national
      cancer incidence and exposure data, and published relative risks. RESULTS: For
      the year 2018 we estimated the smoking-attributable cancer burden to be 85 072
      cases (men 58 760, women 26 312), corresponding to 19% of all incident cancers.
      The highest PAF was seen for lung cancer: 89% of male and 83% of female lung
      cancer cases are attributable to smoking. The cancer burden attributable to high
      alcohol consumption was estimated to be 9588 (men 8117, women 1471) cases (2% of
      all incident cancers). The highest PAF were observed for cancer of the oral
      cavity and pharynx (men 34%, women 6%) and squamous cell carcinoma of the
      esophagus (men 30%; women 5%). CONCLUSIONS: A considerable proportion of cancer
      cases are attributable to smoking and high alcohol consumption. More rigorous
      prevention efforts are required to achieve significant reductions in the
      prevalence of these risk factors and the attributable cancer burden.

PMID- 30236217
TI  - The Differential Diagnosis of Light-Red Livor Mortis.

PMID- 30236219
TI  - Increase in Risk of Acute Confusional State in Dementia Patients.

PMID- 30236218
TI  - Cancers Due to Infection and Selected Environmental Factors.
AB  - BACKGROUND: Causal relationships with the occurrence of cancer have been
      established for a number of infections and environmental risk factors. METHODS:
      Numbers and proportions (population-attributable fractions, PAF) of cancer cases
      attributable to these factors in Germany were calculated by sex and age groups
      for ages 35 to 84 years based on population projections, national cancer
      incidence, exposure data, and published risk estimates. RESULTS: For 2018, more
      than 17 600 cancer cases (4.0% of all incident cancers) were estimated to be
      attributable to infections. The largest contributions come from Helicobacter
      pylori (n = 8764) and human papillomavirus (n = 7669) infections. Infection with
      hepatitis B and C, human immunodeficiency virus, and human herpesvirus 8 were
      estimated to cause 983 cases, 144 cases, and 116 cases, respectively. More than
      5400 cancer cases (1.2% of all incident cancers) were estimated to be
      attributable to selected environmental factors, of which the largest contributor
      is indoor radon (n = 3185), followed by particulate matter (n = 1049), sunbed use
      (n = 892), and secondhand smoke (n = 309). CONCLUSION: Of all cancers expected in
      2018 in Germany, at least 5% are attributable to potentially avoidable infections
      and environmental factors. Further research should be directed towards more
      comprehensive identification and quantification of environmental risks as a basis
      for targeted cancer prevention.

PMID- 30236220
TI  - In Reply.

PMID- 30236216
TI  - Cancers Due to Excess Weight, Low Physical Activity, and Unhealthy Diet.
AB  - BACKGROUND: Excess weight, low physical activity, low intakes of dietary fiber,
      fruits, and vegetables, and high meat and salt intake increase cancer risk.
      METHODS: Numbers and proportions (population-attributable fractions, PAF) of
      incident cancer cases in Germany in 2018 attributable to these factors were
      estimated by sex and age groups for ages 35 to 84 years using population
      projections, national cancer incidence and exposure data, and published risk
      estimates. RESULTS: Estimated numbers (percentages) of attributable cancers were
      30 567 (7%) for excess weight, 27 081 (6%) for low physical activity, 14 474 (3%)
      for low dietary fiber intake, 9447 (2%) for low fruit and vegetable consumption,
      9454 (2%) and 1687 (0.4%) for processed meat and high red meat consumption,
      respectively, and 1204 (0.3%) for high salt intake. Excess weight substantially
      contributed to endometrial, renal, and liver cancer (PAF = 24 to 35%). Low
      physical activity contributed to endometrial, renal, and lung cancer (PAF = 15 to
      19%), and dietary factors mainly contributed to colorectal, breast, and lung
      cancer (PAF = 9 to 16%). CONCLUSION: A considerable proportion of cancer cases
      are attributable to excess weight, physical inactivity, and unhealthy dietary
      habits. Major prevention efforts are needed to reduce the cancer incidence
      attributable to these avoidable factors.

PMID- 30236221
TI  - Tendon Swelling After Kidney Transplantation.

PMID- 30236222
TI  - Radiotherapy.

PMID- 30236223
TI  - Autologous Fat Transplantation.

PMID- 30236224
TI  - In Reply.

PMID- 30236225
TI  - Centrifugal Surgery.

PMID- 30236226
TI  - In Reply.

PMID- 30236227
TI  - Making sense of the impact of intraoperative hypotension: from populations to the
      individual patient.

PMID- 30236228
TI  - Counting the cost of cancelled surgery: a system wide approach is needed.

PMID- 30236229
TI  - Sugammadex: the sting in the tail?

PMID- 30236230
TI  - Implications of variation by time of day in post-anaesthesia care unit length of
      stay for rational nurse staffing.

PMID- 30236231
TI  - Out of Africa: three generalisable lessons about clinical research.

PMID- 30236232
TI  - We may be Homo sapiens, but anaesthetists are merely apes when evaluating risk.

PMID- 30236233
TI  - Intraoperative hypotension and the risk of postoperative adverse outcomes: a
      systematic review.
AB  - BACKGROUND: Intraoperative hypotension is a common side effect of general
      anaesthesia and might lead to inadequate organ perfusion. It is unclear to what
      extent hypotension during noncardiac surgery is associated with unfavourable
      outcomes. METHODS: We conducted a systematic search in PubMed, Embase, Web of
      Science, and CINAHL, and classified the quality of retrieved articles according
      to predefined adapted STROBE and CONSORT criteria. Reported strengths of
      associations from high-quality studies were classified into end-organ specific
      injury risks, such as acute kidney injury, myocardial injury, and stroke, and
      overall organ injury risks for various arterial blood pressure thresholds.
      RESULTS: We present an overview of 42 articles on reported associations between
      various absolute and relative intraoperative hypotension definitions and their
      associations with postoperative adverse outcomes after noncardiac surgery.
      Elevated risks of end-organ injury were reported for prolonged exposure (>=10
      min) to mean arterial pressures <80 mm Hg and for shorter durations <70 mm Hg.
      Reported risks increase with increased durations for mean arterial pressures <65
      60 mm Hg or for any exposure <55-50 mm Hg. CONCLUSIONS: The reported associations
      suggest that organ injury might occur when mean arterial pressure decreases <80
      mm Hg for >=10 min, and that this risk increases with blood pressures becoming
      progressively lower. Given the retrospective observational design of the studies
      reviewed, reflected by large variability in patient characteristics, hypotension
      definitions and outcomes, solid conclusions on which blood pressures under which
      circumstances are truly too low cannot be drawn. We provide recommendations for
      the design of future studies. CLINICAL REGISTRATION NUMBER: (PROSPERO ID).
      CRD42013005171.

PMID- 30236234
TI  - Association between preoperative ambulatory heart rate and postoperative
      myocardial injury: a retrospective cohort study.
AB  - BACKGROUND: Resting heart rate is well established as a predictor of morbidity
      and mortality in the general population. However, the relationship between
      preoperative heart rate and perioperative outcomes, specifically myocardial
      injury, is unclear. METHODS: This retrospective cohort study included patients
      undergoing elective major non-cardiac surgery from 2008 to 2014 at a multisite
      healthcare system. The exposure was ambulatory heart rate measured during the
      outpatient preoperative clinic visit, whereas the outcome of interest was
      myocardial injury (peak postoperative troponin I concentration >30 ng L-1).
      Covariates included patient characteristics, comorbidities, and preoperative
      medications. We constructed several multivariable regression models that each
      modelled heart rate in a different manner, including as a simple continuous
      variable, categories, and fractional polynomials. RESULTS: The cohort included 41
      140 patients, of whom 4857 (11.8%) experienced myocardial injury. Based on pre
      specified heart categories thresholds, a heart rate >=90 beats min-1 was
      associated with an elevated odds of myocardial injury compared with a heart rate
      <60 beats min-1 (adjusted odds ratio, 1.22; 95% confidence interval, 1.06-1.39;
      P=0.005). This result was consistent regardless of the method used for
      categorisation. When fractional polynomials were used to model heart rate, a 'J
      shaped' relationship between heart rate and odds of myocardial injury was
      observed. CONCLUSIONS: This cohort study found that both very high preoperative
      heart rates, and possibly also very low heart rates, are associated with
      increased risk of myocardial injury. Whether heart rate is a modifiable risk
      factor, or rather simply a marker of underlying cardiac pathology, needs to be
      determined in further research.

PMID- 30236240
TI  - Diurnal variations in recovery times after general anaesthesia in children.
AB  - BACKGROUND: Circadian rhythms coordinate almost all physiological functions and
      are implicated in major disease development. Even though circadian rhythms have a
      major impact on human health, little is known about how they affect general
      anaesthesia. The purpose of this study was to understand if the time of day
      affects the length of time a child needs to achieve readiness for discharge after
      general anaesthesia for brain MRI. METHODS: A retrospective analysis over a 3 yr
      period (2013-5) on the length of stay in the postanaesthesia care unit (PACU)
      before discharge was performed for children (age <18 yr) undergoing brain
      magnetic resonance imaging as outpatients. PACU duration was correlated to either
      morning vs afternoon or to time clusters for discharge times (<9 AM, >9 AM <12
      PM, >12 PM <3 PM, >3 PM <6 PM, >6 PM). RESULTS: Data from 2340 procedures in
      children, with median age [inter-quartile range (range)] of 4.7 [2.3-7.25 (0.5
      17.8)] yr were available for analysis. The length of stay in the PACU
      significantly increased over the course of the day with an observed maximum
      increase of 18 or 19 min (<9 AM vs >6 PM) in children older than 3 or 5 yr,
      respectively. Subgroup analysis suggested time of day dependent PACU time
      increase was independent of sex, co-medications, or obstructive sleep apnoea.
      CONCLUSION: The time of day significantly affects PACU recovery times in children
      of both genders having brain imaging under general anaesthesia. Children younger
      than 3 yr might not be affected. Further validation of these findings may guide
      future strategies to reduce discharge times.

PMID- 30236239
TI  - Targeted temperature management in patients with intracerebral haemorrhage,
      subarachnoid haemorrhage, or acute ischaemic stroke: consensus recommendations.
AB  - BACKGROUND: A modified Delphi approach was used to identify a consensus on
      practical recommendations for the use of non-pharmacological targeted temperature
      management in patients with intracerebral haemorrhage, subarachnoid haemorrhage,
      or acute ischaemic stroke with non-infectious fever (assumed neurogenic fever).
      METHODS: Nine experts in the management of neurogenic fever participated in the
      process, involving the completion of online questionnaires, face-to-face
      discussions, and summary reviews, to consolidate a consensus on targeted
      temperature management. RESULTS: The panel's recommendations are based on a
      balance of existing evidence and practical considerations. With this in mind,
      they highlight the importance of managing neurogenic fever using a single
      protocol for targeted temperature management. Targeted temperature management
      should be initiated if the patient temperature increases above 37.5 degrees C,
      once an appropriate workup for infection has been undertaken. This helps prevent
      prophylactic targeted temperature management use and ensures infection is
      addressed appropriately. When neurogenic fever is detected, targeted temperature
      management should be initiated rapidly if antipyretic agents fail to control the
      temperature within 1 h, and should then be maintained for as long as there is
      potential for secondary brain damage. The recommended target temperature for
      targeted temperature management is 36.5-37.5 degrees C. The use of advanced
      targeted temperature management methods that enable continuous, or near
      continuous, temperature measurement and precise temperature control is
      recommended. CONCLUSIONS: Given the limited heterogeneous evidence currently
      available on targeted temperature management use in patients with neurogenic
      fever and intracerebral haemorrhage, subarachnoid haemorrhage, or acute ischaemic
      stroke, a Delphi approach was appropriate to gather an expert consensus. To aid
      in the development of future investigations, the panel provides recommendations
      for data gathering.

PMID- 30236237
TI  - Hypersensitivity incidence after sugammadex administration in healthy subjects: a
      randomised controlled trial.
AB  - BACKGROUND: We evaluated the incidence of hypersensitivity or anaphylaxis after
      repeated single-dose sugammadex administration in non-anaesthetised adults.
      METHODS: In this multicentre, double-blind study (NCT02028065), healthy volunteer
      subjects were randomised (2:2:1 ratio) to one of three groups to receive three
      repeated intravenous injections of sugammadex 4 or 16 mg kg-1, or placebo,
      separated by a ~5 week intervals. Targeted hypersensitivity assessments were
      performed 0.5, 4, and 24 h post-dosing, and hypersensitivity signs/symptoms were
      referred to a blinded independent Adjudication Committee. Anaphylaxis was
      determined per Sampson (Criterion 1). The primary endpoint was the proportion
      with confirmed hypersensitivity. RESULTS: Of 375 evaluable subjects, 25 had
      confirmed hypersensitivity [sugammadex 4 mg kg-1: 10/151 (6.6%); sugammadex 16 mg
      kg-1: 14/148 (9.5%); placebo: 1/76 (1.3%)]. The differences in incidence rates vs
      placebo were 5.3% (95% confidence interval: -0.9, 10.7) for sugammadex 4 mg kg-1
      and 8.1% (1.7, 14.2) for 16 mg kg-1. Incidence was similar across sugammadex
      doses and dosing occasions, including in subjects with reactions to previous
      doses. Three subjects (16 mg kg-1 group) required antihistamines/corticosteroids
      and discontinued the study, per protocol; symptoms resolved and no subject
      required epinephrine. One subject with anaphylaxis after the first 16 mg kg-1
      dose recovered completely post-treatment. There were no clinically relevant anti
      sugammadex antibody or tryptase findings. CONCLUSIONS: Hypersensitivity in
      response to sugammadex administration can occur in healthy subjects without
      history of previous sugammadex exposure. Hypersensitivity incidence was similar
      across sugammadex doses and numerically higher than placebo, with no evidence of
      sensitisation with repeated administration. Hypersensitivity is unlikely to be
      mediated through sugammadex-specific immunoglobulin G- or E-mediated mast cell
      stimulation in healthy volunteers. CLINICAL TRIAL REGISTRATION: NCT02028065.

PMID- 30236236
TI  - Development and internal validation of a novel risk adjustment model for adult
      patients undergoing emergency laparotomy surgery: the National Emergency
      Laparotomy Audit risk model.
AB  - BACKGROUND: Among patients undergoing emergency laparotomy, 30-day postoperative
      mortality is around 10-15%. The risk of death among these patients, however,
      varies greatly because of their clinical characteristics. We developed a risk
      prediction model for 30-day postoperative mortality to enable better comparison
      of outcomes between hospitals. METHODS: We analysed data from the National
      Emergency Laparotomy Audit (NELA) on patients having an emergency laparotomy
      between December 2013 and November 2015. A prediction model was developed using
      multivariable logistic regression, with potential risk factors identified from
      existing prediction models, national guidelines, and clinical experts. Continuous
      risk factors were transformed if necessary to reflect their non-linear
      relationship with 30-day mortality. The performance of the model was assessed in
      terms of its calibration and discrimination. Interval validation was conducted
      using bootstrap resampling. RESULTS: There were 4458 (11.5%) deaths within 30
      days among the 38 830 patients undergoing emergency laparotomy. Variables
      associated with death included (among others): age, blood pressure, heart rate,
      physiological variables, malignancy, and ASA physical status classification. The
      predicted risk of death among patients ranged from 1% to 50%. The model
      demonstrated excellent calibration and discrimination, with a C-statistic of
      0.863 (95% confidence interval, 0.858-0.867). The model retained its high
      discrimination during internal validation, with a bootstrap derived C-statistic
      of 0.861. CONCLUSIONS: The NELA risk prediction model for emergency laparotomies
      discriminates well between low- and high-risk patients and is suitable for
      producing risk-adjusted provider mortality statistics.

PMID- 30236241
TI  - Evidence-based management of pain after laparoscopic cholecystectomy: a PROSPECT
      review update.
AB  - BACKGROUND: Significant pain can be experienced after laparoscopic
      cholecystectomy. This systematic review aims to formulate PROSPECT (PROcedure
      SPECific Postoperative Pain ManagemenT) recommendations to reduce postoperative
      pain after laparoscopic cholecystectomy. METHODS: Randomised controlled trials
      published in the English language from January 2006 (date of last PROSPECT
      review) to December 2017, assessing analgesic, anaesthetic, or operative
      interventions for laparoscopic cholecystectomy in adults, and reporting pain
      scores, were retrieved from MEDLINE and Cochrane databases using PRISMA
      (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) search
      protocols. PROSPECT methodology was used, and recommendations were formulated
      after review and discussion by the PROSPECT group (an international group of
      leading pain specialists and surgeons). RESULTS: Of 1988 randomised controlled
      trials identified, 258 met the inclusion criteria and were included in this
      review. The studies were of mixed methodological quality, and quantitative
      analysis was not performed because of heterogeneous study design and how outcomes
      were reported. CONCLUSIONS: We recommend basic analgesic techniques: paracetamol
      + NSAID or cyclooxygenase-2 specific inhibitor + surgical site local anaesthetic
      infiltration. Paracetamol and NSAID should be started before or during operation
      with dexamethasone (GRADE A). Opioid should be reserved for rescue analgesia only
      (GRADE B). Gabapentanoids, intraperitoneal local anaesthetic, and transversus
      abdominis plane blocks are not recommended (GRADE D) unless basic analgesia is
      not possible. Surgically, we recommend low-pressure pneumoperitoneum,
      postprocedure saline lavage, and aspiration of pneumoperitoneum (GRADE A). Single
      port incision techniques are not recommended to reduce pain (GRADE A).

PMID- 30236238
TI  - Sugammadex hypersensitivity and underlying mechanisms: a randomised study of
      healthy non-anaesthetised volunteers.
AB  - BACKGROUND: We investigated potential for hypersensitivity reactions after
      repeated sugammadex administration and explored the mechanism of
      hypersensitivity. METHODS: In this double-blind, placebo-controlled study
      (NCT00988065), 448 healthy volunteers were randomised to one of three arms to
      receive three repeat i.v. administrations of either sugammadex 4 mg kg-1, 16 mg
      kg-1, or placebo. Primary endpoint was percentage of subjects with
      hypersensitivity (assessed by an independent adjudication committee). Secondary
      endpoint of anaphylaxis was classified per Sampson and Brighton criteria.
      Exploratory endpoints included skin testing, serum tryptase, anti-sugammadex
      antibodies [immunoglobulin (Ig) E/IgG], and other immunologic parameters.
      RESULTS: Hypersensitivity was adjudicated for 1/148 (0.7%), 7/150 (4.7%), and
      0/150 (0.0%) subjects after sugammadex 4 mg kg-1, 16 mg kg-1, and placebo,
      respectively. After sugammadex 16 mg kg-1, one subject met Sampson criterion 1
      and Brighton level 1 (highest certainty) anaphylaxis criteria; two met Brighton
      level 2 criteria. After database lock it was determined that certain protocol
      deviations could have introduced bias in the reporting of hypersensitivity
      signs/symptoms in a subject subset. Objective laboratory investigations indicated
      that potential underlying hypersensitivity mechanisms were unlikely to have been
      activated; the results suggest that most of the observed hypersensitivity
      reactions were unlikely IgE/IgG-mediated. CONCLUSION: Dose-dependent
      hypersensitivity or anaphylaxis reactions to sugammadex were observed when
      administered without prior neuromuscular blocking agent. Laboratory
      investigations do not suggest prevalent allergen-specific IgE/IgG-mediated
      immunologic hypersensitivity. Because it could not be fully excluded that
      estimates of hypersensitivity/anaphylaxis incidence were unbiased, an additional
      study was conducted to characterise the potential for hypersensitivity reactions
      and is described in a companion report. CLINICAL TRIAL REGISTRATION:
      http://www.clinicaltrials.gov NCT00988065; Protocol number P06042.

PMID- 30236243
TI  - Barriers to clinical research in Africa: a quantitative and qualitative survey of
      clinical researchers in 27 African countries.
AB  - BACKGROUND: There is a need for high quality research to improve perioperative
      patient care in Africa. The aim of this study was to understand the particular
      barriers to clinical research in this environment. METHODS: We conducted an
      electronic survey of African Surgical Outcomes Study (ASOS) investigators,
      including 29 quantitative Likert scale questions and eight qualitative questions
      with subsequent thematic analysis. Protocol compliant and non-compliant countries
      were compared according to WHO statistics for research and development, health
      workforce data, and world internet statistics. RESULTS: Responses were received
      from 134/418 of invited researchers in 24/25 (96%) of participating countries,
      and three non-participating countries. Barriers included lack of a dedicated
      research team (47.7%), reliable internet access (32.6%), staff skilled in
      research (31.8%), and team commitment (23.8%). Protocol compliant countries had
      significantly more physicians per 1000 population (4 vs 0.9, P<0.01), internet
      penetration (38% vs 28%, P=0.01) and published clinical trials (1461 vs 208,
      P<0.01) compared with non-compliant countries. Facilitators of research included
      establishing a research culture (86.9%), simple data collection tools (80%), and
      ASOS team interaction (77.9%). Most participants are interested in future
      research (93.8%). Qualitative data reiterated human resource, financial resource,
      and regulatory barriers. However, the desire to contribute to an African
      collaboration producing relevant data to improve patient outcomes was expressed
      strongly by ASOS investigators. CONCLUSIONS: Barriers to successful participation
      in ASOS related to resource limitations and not motivation of the clinician
      investigators. Practical solutions to individual barriers may increase the
      success of multi-centre perioperative research in Africa.

PMID- 30236242
TI  - Persistent postoperative pain after total knee arthroplasty: a prospective cohort
      study of potential risk factors.
AB  - BACKGROUND: Persistent postoperative pain (PPP) is common after total knee
      arthroplasty (TKA). The primary aim of this prospective cohort study was to
      identify important predictors of moderate to severe PPP 6 and 12 months after
      TKA. METHODS: Consenting patients (n=300) undergoing primary unilateral TKA
      attended a preoperative session to collect clinical information (age, gender,
      BMI, preoperative knee pain, comorbid pain, likely neuropathic pain) and
      psychological variables (depression, anxiety, catastrophising, expected pain).
      Quantitative sensory testing (pressure pain thresholds, temporal summation,
      conditioned pain modulation) was performed, and blood samples were obtained for
      subsequent genotyping of OPRM1 and COMT. Acute postoperative pain was measured at
      rest and during movement. Surgical factors (surgery time, patella resurfacing,
      anaesthetic type) were collected after operation. Follow-up questionnaires were
      sent 6 and 12 months after surgery. Multivariate logistic regression was used to
      identify predictors of PPP. RESULTS: The prevalence of moderate to severe PPP was
      21% (n=60) and 16% (n=45) 6 and 12 months after surgery, with 55% (n=33) and 60%
      (n=31) of PPP likely neuropathic in nature. At 6 months, a combination of
      preoperative pain intensity, expected pain, trait anxiety, and temporal summation
      (Akaike information criterion, 309.9; area under receiver operating
      characteristic (ROC) curve, 0.70) was able to correctly classify 66% of patients
      into moderate to severe PPP and no to mild PPP groups. At 12 months, preoperative
      pain intensity, expected pain, and trait anxiety (Akaike information criterion,
      286.8; area under ROC curve, 0.66) correctly classified 66% of patients.
      CONCLUSIONS: Findings from this study highlight several factors that may be
      targeted in future intervention studies to reduce the development of PPP. TRIAL
      REGISTRY NUMBER: ACTRN12612001089820.

PMID- 30236244
TI  - Local anaesthetic-induced myotoxicity in regional anaesthesia: a systematic
      review and empirical analysis.
AB  - Recent reports of local-anaesthetic (LA)-induced myotoxicity after peripheral
      nerve blocks have increased the interest in this less commonly known
      complication. Basic science evidence investigating LA-induced myotoxicity seems
      to demonstrate a pattern, but findings from human studies vary. This systematic
      review summarises the existing myotoxicity evidence and empirically examines its
      implications. Databases were searched for all in vitro animal and human studies
      evaluating LA-induced myotoxicity. Studies were stratified by design. Data sought
      included the model examined, LA used, injury mechanisms, nature of damage, and
      extent of recovery. For human studies, we also aimed to estimate prevalence and
      recovery rates. One hundred and fifteen studies, mainly animal and ophthalmic,
      were included. Myotoxicity risk factors included higher concentrations and
      prolonged exposure to LA, and use of bupivacaine. Injury mechanisms involved
      early and late aberrations to cytoplasmic calcium (Ca2+) homeostasis by the
      sarcoplasmic reticulum Ca2+ ATPase. Incidence in ophthalmic studies was 0.77%
      (392 of 50 618). Inflammatory changes within a few days after exposure marked the
      onset of myotoxicity, and myo-degeneration followed within the first week post
      exposure. Time to recovery in human muscles ranged between 4 days to 1 yr.
      None/partial and complete recovery were observed in 61% and 38% of patients,
      respectively. Across all experimental models, skeletal muscles exposed to LA
      consistently display myotoxic effects. Evidence is robust in animal and
      ophthalmic studies, and displays a concerning signal with continuous adductor
      canal block use in human case reports. Exploring the clinical prevalence,
      severity, and risk-reducing strategies of myotoxicity should be prioritised.

PMID- 30236245
TI  - Neuraxial anaesthesia techniques and postoperative outcomes among joint
      arthroplasty patients: is spinal anaesthesia the best option?
AB  - BACKGROUND: Neuraxial anaesthesia is frequently used for lower limb arthroplasty
      but it is unclear whether benefits vary among patients receiving different
      subtypes of neuraxial anaesthesia. We evaluated whether differences in risk for
      adverse postoperative outcomes exist between patients receiving combined spinal
      and epidural (CSE), epidural, or spinal anaesthesia. METHODS: In this
      retrospective cohort study, we identified 40 852 patients who underwent total hip
      and knee arthroplasty (THA and TKA) procedures under neuraxial anaesthesia (34
      301 CSE, 2464 epidural, 4087 spinal) between 2005 and 2014 at a single
      institution. We used multivariable logistic regression to evaluate the following
      outcomes: cardiac, pulmonary, gastrointestinal, renal/genitourinary, and
      thromboembolic complications, and prolonged length of stay. RESULTS: Compared
      with CSE, spinal anaesthesia was associated with reduced adjusted odds for
      cardiac [odds ratio (OR), 0.68; 95% confidence interval (CI), 0.52-0.89],
      pulmonary (OR: 0.51; 95% CI: 0.38-0.68), gastrointestinal (OR: 0.50; 95% CI: 0.32
      0.78), and thromboembolic complications (OR: 0.40; 95% CI: 0.23-0.73), and
      prolonged length of stay (OR: 0.72; 95% CI: 0.66-0.80). Patients who received
      epidural anaesthesia did not have significantly different odds for any outcomes
      compared with CSE patients. CONCLUSIONS: We identified clear differences in risk
      for certain postoperative events by subtype of neuraxial anaesthesia, suggesting
      that spinal anaesthesia is associated with the most favourable outcomes profile.

PMID- 30236247
TI  - Blood flow index as an indicator of successful sciatic nerve block: a prospective
      observational study using laser speckle contrast imaging.
AB  - BACKGROUND: Laser speckle contrast imaging allows real-time, non-invasive,
      quantitative measurements of regional blood flow. The objectives of this
      prospective observational study were to use laser speckle contrast imaging to
      evaluate blood flow changes after sciatic nerve block, and to determine whether
      this novel optical technique can evaluate block success. METHODS: This
      observational study included 63 adult patients undergoing elective lower limb
      surgery with sciatic nerve block. Blood flow images and blood flow index (BFI)
      values of toes were recorded using laser speckle contrast imaging 5 min before
      nerve block and at 5 min intervals until 30 min after sciatic block. The
      sensitivity, specificity, and cut-off value of laser speckle contrast imaging for
      predicting successful sciatic block were determined by receiver operator
      characteristic (ROC) curve analysis. RESULTS: The BFI values of toes were
      significantly increased at each time point after successful sciatic block,
      compared with the baseline value obtained 5 min before nerve block; in failed
      sciatic block, there were no significant differences. For successful sciatic
      block, the highest increase of BFI value was at the big toe. BFI increase of the
      big toe at 10 min after sciatic block has great potential as an indicator of
      block success. The area under the ROC curve was 0.954 at a cut-off value of 8.48
      perfusion units (PU) with a sensitivity of 89% and a specificity of 100%.
      CONCLUSIONS: Laser speckle contrast imaging might be an early, objective,
      quantitative, and reliable indicator of successful sciatic block. BFI increase of
      the big toe not reaching 8.48 PU within 10 min after sciatic block indicates
      block failure. CLINICAL TRIAL REGISTRATION: NCT03169517.

PMID- 30236246
TI  - Femoral nerve catheter vs local infiltration for analgesia in fast track total
      knee arthroplasty: short-term and long-term outcomes.
AB  - BACKGROUND: The aim was to compare the effects on short-term and long-term pain
      and functional outcome of periarticular local anaesthetic infiltration (LIA) with
      LIA of the posterior knee capsule in combination with a femoral nerve block (FNB)
      catheter in patients undergoing total knee arthroplasty. METHODS: Eighty patients
      were randomised to one of two groups: Subjects in group LIA received
      periarticular LIA with ropivacaine 0.2% for postoperative analgesia; subjects in
      group FNB received LIA of the posterior capsule and a FNB catheter. The primary
      outcome parameter was functional capacity of the knee 12 months after surgery.
      Secondary parameters included mobility as determined by accelerometer data, pain,
      satisfaction with the analgesic regimen, hospital length of stay, and use of pain
      medication 3 and 12 months after surgery. RESULTS: There were no differences
      between groups in long-term functional capacity, patient satisfaction and
      hospital length of stay. In the first 2 days, subjects in group FNB had slightly
      lower pain scores and used less opioids, and subjects in group LIA had a higher
      level of accelerometer activity. Three and 12 months after surgery, subjects in
      group FNB had lower maximum pain scores and were less likely to use any pain
      medication 12 months after surgery. CONCLUSIONS: Both techniques were similar
      regarding long-term functional outcome. Subjects in group FNB had slightly lower
      pain scores and lower opioid consumption after operation, lower maximum pain
      scores at 3 and 12 months, and were less likely to use any pain medication at 12
      months. CLINICAL TRIAL REGISTRATION: NCT01966263.

PMID- 30236249
TI  - Fascial layers influence the spread of injectate during ultrasound-guided
      infraclavicular brachial plexus block: a cadaver study.
AB  - BACKGROUND: Fascial layers of the neurovascular sheath containing the brachial
      plexus influence distribution of local anaesthetic, hence increasing the risk of
      block failure when performing infraclavicular brachial plexus block (ICB).
      METHODS: Ultrasound-guided infraclavicular brachial plexus block was performed on
      cadavers using a single injection technique with dye (20-30 ml). After injection,
      we carried out consecutive dissection of the neurovascular bundle to study dye
      injectate spread and identify the presence of fascial layers. Ultrasound video
      images (scout scan and injection) and recordings of dissections were evaluated by
      independent experts (regional anaesthetists and anatomists). RESULTS: Well
      defined fascial layers were identified at dissection in seven out of 12
      infraclavicular spaces studied. These fascial layers impeded the spread of dye
      injectate substantially in six cases and partially in one case. No fascial layers
      were identified at dissection in five cases, in each of which the spread of
      injectate was complete throughout the neurovascular bundle. The sensitivity and
      specificity of ultrasonography and haptic sensation for detection of fascial
      layers were poor. CONCLUSIONS: When fascial layers are present in the
      neurovascular sheath, they impede the spread of injectate during infraclavicular
      brachial plexus block. Ultrasound detection of these fascial layers is unreliable
      in cadavers. These findings support the use of greater volumes of injectate or a
      multiple injection technique when performing this block.

PMID- 30236248
TI  - Validity and reliability of an objective structured assessment tool for
      performance of ultrasound-guided regional anaesthesia.
AB  - BACKGROUND: We examined the validity and reliability of the previously developed
      criterion-referenced assessment checklist (AC) and global rating scale (GRS) to
      assess performance in ultrasound-guided regional anaesthesia (UGRA). METHODS:
      Twenty-one anaesthetists' single, real-time UGRA procedures (total: 21 blocks)
      were assessed using a 22-item AC and a 9-item GRS scored on 3-point and 5-point
      Likert scales, respectively. We used one-way analysis of variance to compare the
      assessment scores between three groups (Group 1: <=30 blocks in the preceding
      year; Group 2: 31-100; and Group 3: >100). The concurrent validity was evaluated
      using Pearson's correlation (r). We calculated Type A intra-class correlation
      coefficient using an absolute-agreement definition in two-way random effects
      model, and inter-rater reliability using an absolute agreement between raters.
      The inter-item consistency was assessed by Cronbach's alpha. RESULTS: The greater
      UGRA experience in the preceding year was associated with better AC [F (2, 18)
      12.01; P<0.001] and GRS [F (2, 18) 7.44; P=0.004] scores. There was a strong
      correlation between the mean AC and GRS scores [r=0.73 (P<0.001)], and a strong
      inter-item consistency for AC (alpha=0.94) and GRS (alpha=0.83). The intra-class
      correlation coefficient (95% confidence interval) and inter-rater reliability
      (95% confidence interval) for AC were 0.96 (0.95-0.96) and 0.91 (0.88-0.95),
      respectively, and 0.93 (0.90-0.94) and 0.80 (0.74-0.86) for GRS. CONCLUSIONS:
      Both assessments differentiated between individuals who had performed fewer
      (<=30) and many (>100) blocks in the preceding year, supporting construct
      validity. It also established concurrent validity and overall reliability. We
      recommend that both tools can be used in UGRA assessment.

PMID- 30236250
TI  - Ultrasound-guided anterior approach to the axillary and intercostobrachial nerves
      in the axillary fossa: an anatomical investigation.
AB  - BACKGROUND: The posterolateral and medial aspect of the arm is supplied by the
      axillary (AXN) and intercostobrachial nerves (ICBN), which are not anaesthetised
      by an axillary brachial plexus block (ABPB). Blockade of the AXN and the ICBN has
      been reported in the quadrangular space (QS) posteriorly or by serratus plane
      block, respectively. An anterior ultrasound-guided approach to block the AXN and
      ICBN would be desirable to complete an ABPB at a single insertion site. METHODS:
      After a preliminary dissection study in six cadavers, ultrasound-guided AXN and
      ICBN injection was performed in 46 Thiel embalmed cadavers bilaterally. Key
      sonographic landmarks to identify the AXN in the QS are the humerus, teres major
      muscle, and subscapular muscle. With the same probe position, the ICBN was
      identified in the subfascial axillary space. Then, 2 ml latex was injected at
      each nerve and confirmed by dissection. RESULTS: Muscular and bony landmarks were
      identified in all cadavers. The AXN was seen in 99% in the QS or at the
      inferolateral margin of the subscapular muscle and surrounded by latex in 96% of
      cases. Latex spread to the axillary fossa, within the subscapular muscle, or to
      the radial nerve was noted in 8% of the injections. The ICBN was seen and
      surrounded by latex in 100% of cases. CONCLUSIONS: We describe a reliable
      ultrasonographic approach to visualise the AXN and ICBN anteriorly from the
      conventional ABPB approach as confirmed in this cadaver study.

PMID- 30236251
TI  - Ultrasound-guided adductor canal block: a cadaver study investigating the effect
      of a thigh tourniquet.
AB  - BACKGROUND: Placement of local anaesthetic within the adductor canal using
      ultrasonography is an alternative to femoral nerve blocks for postoperative pain
      relief after knee joint replacement surgery. However, the effect of an inflated
      thigh tourniquet on the distribution of local anaesthetic within the adductor
      canal is unknown. The aim of this cadaveric study was to compare the distribution
      of radio-opaque dye within the adductor canal in the presence or absence of an
      inflated thigh tourniquet. METHODS: Bilateral ultrasound-guided adductor canal
      blocks were performed on the thawed lower limbs of five fresh frozen human
      cadavers. The left and right lower cadaver limbs were randomised to receive or
      not receive a thigh tourniquet inflated to 300 mm Hg for 1 h. X-rays with iohexol
      radio-opaque dye were obtained in four views, and fiducial markers inserted as
      reference points. Virtual editing technology was used to recreate outlines
      representing the distribution of the radio-opaque dye and superimpose these on
      anatomical images. RESULTS: Radio-opaque dye was distributed on the medial aspect
      of the thighs with entire and well circumscribed margins. The majority of the
      radio-opaque dye was confined within the adductor canal. Superior-inferior dye
      distribution was 315 mm [95% confidence intervals (CI) 289-342] and 264 mm (95%
      CI 239-289) in the presence and absence of an inflated thigh tourniquet,
      respectively (diff 95% CI -80.46 to -22.22, P=0.0081). Image analysis using the
      recreated radio-opaque outlines suggested that the most proximal point of the
      radio-opaque dye was 100 mm (95% CI 82-117) or 117 mm (95% CI 62-171) below the
      inguinal ligament in the presence and absence of an inflated thigh tourniquet,
      respectively (diff 95% CI -38 to 72, P=0.456). CONCLUSIONS: Application and
      inflation of thigh tourniquets significantly increased the combined superior
      inferior dye distribution within the adductor canal of cadaveric limbs. There was
      insufficient evidence to suggest significant proximal spread of 25 ml of local
      anaesthetic to involve the motor branches of the femoral nerve. In some patients,
      the local anaesthetic may reach the popliteal fossa in close approximation to the
      sciatic nerve.

PMID- 30236252
TI  - Intraoperative ventilation settings and their associations with postoperative
      pulmonary complications in obese patients.
AB  - BACKGROUND: There is limited information concerning the current practice of
      intraoperative mechanical ventilation in obese patients, and the optimal
      ventilator settings for these patients are debated. We investigated
      intraoperative ventilation parameters and their associations with the development
      of postoperative pulmonary complications (PPCs) in obese patients. METHODS: We
      performed a secondary analysis of the international multicentre Local ASsessment
      of VEntilatory management during General Anesthesia for Surgery' (LAS VEGAS)
      study, restricted to obese patients, with a predefined composite outcome of PPCs
      as primary end-point. RESULTS: We analysed 2012 obese patients from 135 hospitals
      across 29 countries in Europe, North America, North Africa, and the Middle East.
      Tidal volume was 8.8 [25th-75th percentiles: 7.8-9.9] ml kg-1 predicted body
      weight, PEEP was 4 [1-5] cm H2O, and recruitment manoeuvres were performed in
      7.7% of patients. PPCs occurred in 11.7% of patients and were independently
      associated with age (P<0.001), body mass index >=40 kg m-2 (P=0.033), obstructive
      sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure
      (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment
      manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an
      increased length of hospital stay (P<0.001). CONCLUSIONS: Obese patients are
      frequently ventilated with high tidal volume and low PEEP, and seldom receive
      recruitment manoeuvres. PPCs increase hospital stay, and are associated with
      preoperative conditions, duration of anaesthesia and intraoperative ventilation
      settings. Randomised trials are warranted to clarify the role of different
      ventilatory parameters in obese patients. CLINICAL TRIAL REGISTRATION:
      NCT01601223.

PMID- 30236254
TI  - Comparison between neurally-assisted, controlled, and physiologically variable
      ventilation in healthy rabbits.
AB  - BACKGROUND: Various ventilation strategies have been proposed to reduce
      ventilation-induced lung injury that occurs even in individuals with healthy
      lungs. We compared new modalities based on an individualised physiological
      variable ventilation model to a conventional pressure-controlled mode. METHODS:
      Rabbits were anaesthetised and ventilated for up to 7 h using pressure-controlled
      ventilation with (Group PCS, n=10), and without (Group PC, n=10) regular sighs.
      Variable ventilation in the other two groups was achieved via a pre-recorded
      spontaneous breathing pattern [Group physiologically variable ventilation (PVV),
      n=10] or triggered by the electrical activity of the diaphragm [Group neurally
      adjusted ventilation assist (NAVA), n=9]. Respiratory elastance, haemodynamic
      profile, and gas exchange were assessed throughout the ventilation period.
      Cellular profile, cytokine content of bronchoalveolar lavage fluid, and wet-to
      dry lung weight ratio (W/D) were determined after protocol completion. Lung
      injury scores were obtained from histological analysis. RESULTS: Marked
      deteriorations in elastance were observed (median and 95% confidence interval) in
      Group PC [48.6 (22)% increase from baseline], while no changes were detected in
      Groups PCS [3.6 (8.1)%], PVV [18.7 (13.2)%], and NAVA [-1.4 (12.2)%]. In
      comparison with Group PC, Group PVV had a lower lung injury score [0.29 (0.02)
      compared with 0.36 (0.05), P<0.05] and W/D ratio [5.6 (0.1) compared with 6.2
      (0.3), P<0.05]. There was no difference in blood gas, haemodynamic, or
      inflammatory parameters between the groups. CONCLUSIONS: Individualised PVV based
      on a pre-recorded spontaneous breathing pattern provides adequate gas exchange
      and promotes a level of lung protection. This ventilation modality could be of
      benefit during prolonged anaesthesia, in which assisted ventilation is not
      possible because of the absence of a respiratory drive.

PMID- 30236255
TI  - Cardiogenic oscillations to detect intratidal derecruitment and overdistension in
      a porcine model of healthy and atelectatic lungs.
AB  - BACKGROUND: Low positive end-expiratory pressure (PEEP) can result in alveolar
      derecruitment, and high PEEP or high tidal volume (VT) in lung overdistension. We
      investigated cardiogenic oscillations (COS) in the airway pressure signal to
      investigate whether these oscillations can assess unfavourable intratidal events.
      COS induce short instantaneous compliance increases within the pressure-volume
      curve, and consequently in the compliance-volume curve. We hypothesised that
      increases in COS-induced compliance reflect non-linear intratidal respiratory
      system mechanics. METHODS: In mechanically ventilated anaesthetised pigs with
      healthy (n=13) or atelectatic (n=12) lungs, pressure-volume relationships and the
      ECG were acquired at a PEEP of 0, 5, 10, and 15 cm H2O. During inspiration, the
      peak compliance of successive COS (CCOS) was compared with intratidal respiratory
      system compliance (CRS) within incremental volume steps up to the full VT of 12
      ml kg-1. We analysed whether CCOS variation corresponded with systolic arterial
      pressure variation. RESULTS: CCOS-volume curves showed characteristic intratidal
      patterns depending on the PEEP level and on atelectasis. Increasing CRS- or CCOS
      volume patterns were associated with intratidal derecruitment with low PEEP, and
      decreasing patterns above 6 ml kg-1 and high PEEP showed overdistension. CCOS was
      not associated with systolic arterial pressure variations. CONCLUSIONS: Heartbeat
      induced oscillations within the course of the inspiratory pressure-volume curve
      reflect non-linear intratidal respiratory system mechanics. The analysis of these
      cardiogenic oscillations can be used to detect intratidal derecruitment and
      overdistension and, hence, to guide PEEP and VT settings that are optimal for
      respiratory system mechanics.

PMID- 30236256
TI  - Factor IX from prothrombin complex concentrate augments low dose tissue factor
      triggered thrombin generation in vitro.
AB  - BACKGROUND: Prothrombin complex concentrate (PCC) is increasingly used to correct
      acquired coagulopathy in trauma and surgery. Dosing of PCC is guided by the
      prothrombin time, which only reflects the onset of thrombin generation, but does
      not account for variations in intrinsic pathway coagulation factors, including
      factor IX (FIX). We hypothesised that FIX contained in PCC could strongly
      influence thrombin generation patterns. METHODS: Pooled normal, FIX-deficient,
      and warfarinised plasma were used to analyse the effects of FIX contained in PCC.
      PCC was evaluated at final concentrations of 0.2 and 0.4 IU ml-1 in FIX-deficient
      and normal plasma, and at 0.6 IU ml-1 in warfarinised plasma with elevated FVIII
      (1.5 IU ml-1), 40% dilution with saline, or both. The effects on thrombin
      generation were assessed by measuring both procoagulant and inhibitory segments.
      RESULTS: FIX-deficient plasma had lower peak thrombin generation [30.6 (20.5
      35.8) nM vs 130.2 (107-168) nM] and endogenous thrombin potential [472 (391-532)
      nM vs 1096 (958-1190) nM] than normal plasma. PCC addition resulted in
      significant increases of peak thrombin generation [81.8 (37.3-98.3) nM] and
      endogenous thrombin potential [808 (472-842) nM] in FIX-deficient plasma. The
      combination of FVIII and PCC resulted in greater increases relative to each agent
      alone, restoring normal thrombin generation. After 40% dilution, adding PCC,
      FVIII, or both, to FIX-deficient plasma increased peak thrombin generation, and
      prolonged the inhibitory phase of the endogenous thrombin potential. CONCLUSIONS:
      FIX derived from PCC strongly enhances tissue factor-triggered thrombin
      generation in the presence of elevated FVIII activity. Haemodilution further
      enhances procoagulant effects of FIX and FVIII by slowing down inhibition of
      procoagulant enzymes. Dosing of PCC per prothrombin time may underestimate PCC's
      procoagulant potential because it does not account for intrinsic tenase or
      antithrombin activity.

PMID- 30236253
TI  - Adoption of Lung Protective ventilation IN patients undergoing Emergency
      laparotomy: the ALPINE study. A prospective multicentre observational study.
AB  - BACKGROUND: Emergency abdominal surgery is associated with a high risk of
      postoperative pulmonary complications (PPCs). The primary aim of this study was
      to determine whether patients undergoing emergency laparotomy are ventilated
      using a lung-protective ventilation strategy employing tidal volume <=8 ml kg-1
      ideal body weight-1, PEEP >5 cm H2O, and recruitment manoeuvres. The secondary
      aim was to investigate the association between ventilation factors (lung
      protective ventilation strategy, intraoperative FiO2, and peak inspiratory
      pressure) and the occurrence of PPCs. METHODS: Data were collected prospectively
      in 28 hospitals across London as part of routine National Emergency Laparotomy
      Audit (NELA). Patients were followed for 7 days. Complications were defined
      according to the European Perioperative Clinical Outcome definition. RESULTS:
      Data were collected from 568 patients. The median [inter-quartile range (IQR)]
      tidal volume observed was 500 ml (450-540 ml), corresponding to a median tidal
      volume of 8 ml kg-1 ideal body weight-1 (IQR: 7.2-9.1 ml). A lung-protective
      ventilation strategy was employed in 4.9% (28/568) of patients, and was not
      protective against the occurrence of PPCs in the multivariable analysis (hazard
      ratio=1.06; P=0.69). Peak inspiratory pressure of <30 cm H2O was protective
      against development of PPCs (hazard ratio=0.46; confidence interval: 0.30-0.72;
      P=0.001). Median FiO2 was 0.5 (IQR: 0.44-0.53), and an increase in FiO2 by 5%
      increased the risk of developing a PPC by 8% (2.6-14.1%; P=0.008). CONCLUSIONS:
      Both intraoperative peak inspiratory pressure and FiO2 are independent factors
      significantly associated with development of a postoperative pulmonary
      complication in emergency laparotomy patients. Further studies are required to
      identify causality and to demonstrate if their manipulation could lead to better
      clinical outcomes.

PMID- 30236257
TI  - Genetic epidemiology of malignant hyperthermia in the UK.
AB  - BACKGROUND: Gaps in our understanding of genetic susceptibility to malignant
      hyperthermia (MH) limit the application and interpretation of genetic diagnosis
      of the condition. Our aim was to define the prevalence and role of variants in
      the three genes implicated in MH susceptibility in the largest comprehensively
      phenotyped MH cohort worldwide. METHODS: We initially included one individual
      from each positive family tested in the UK MH Unit since 1971 to detect variants
      in RYR1, CACNA1S, or STAC3. Screening for genetic variants has been ongoing since
      1991 and has involved a range of techniques, most recently next generation
      sequencing. We assessed the pathogenicity of variants using standard guidelines,
      including family segregation studies. The prevalence of recurrent variants of
      unknown significance was compared with the prevalence reported in a large
      database of sequence variants in low-risk populations. RESULTS: We have confirmed
      MH susceptibility in 795 independent families, for 722 of which we have a DNA
      sample. Potentially pathogenic variants were found in 555 families, with 25 RYR1
      and one CACNA1S variants previously unclassified recurrent variants significantly
      over-represented (P<1*10-7) in our cohort compared with the Exome Aggregation
      Consortium database. There was genotype-phenotype discordance in 86 of 328
      families suitable for segregation analysis. We estimate non-RYR1/CACNA1S/STAC3
      susceptibility occurs in 14-23% of MH families. CONCLUSIONS: Our data provide
      current estimates of the role of variants in RYR1, CACNA1S, and STAC3 in
      susceptibility to MH in a predominantly white European population.

PMID- 30236260
TI  - Treating patients rather than their functional neuroimages. Comment on Br J
      Anaesth 2018; 120: 299-307.

PMID- 30236259
TI  - Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell
      migration.
AB  - BACKGROUND: The metastatic potential of breast cancer cells has been strongly
      associated with overexpression of the chemokine CXCL12 and the activity of its
      receptor CXCR4. Lidocaine, a local anaesthetic that can be used during breast
      cancer excision, inhibits the growth, invasion, and migration of cancer cells. We
      therefore investigated, in a breast cancer cell line, whether lidocaine can
      modulate CXCL12-induced responses. METHODS: Intracellular calcium, cytoskeleton
      remodelling, and cell migration were assessed in vitro in MDA-MB-231 cells, a
      human breast cancer epithelial cell line, after exposure to lidocaine (10 MUM or
      100 MUM). RESULTS: Lidocaine (10 or 100 MUM) significantly inhibited CXCR4
      signalling, resulting in reduced calcium release (Fluo 340 nm/380 nm, 0.76 mean
      difference, p<0.0001), impaired cytoskeleton remodelling (F-Actin fluorescence
      mean intensity, 21 mean difference, P=0.002), and decreased motility of cancer
      cells, both in the scratch wound assay (wound area at 21 h, -19%, P<0.0001), and
      in chemotaxis experiments (fluorescence mean intensity, 0.16, P=0.0047). The
      effect of lidocaine was not associated with modulation of the CD44 adhesion
      molecule. CONCLUSIONS: At clinical concentrations, lidocaine significantly
      inhibits CXCR4 signalling. The results presented shed new insights on the
      molecular mechanisms governing the inhibitory effect of lidocaine on cell
      migration.

PMID- 30236261
TI  - Brain imaging of analgesic and placebo responses. Comment on Br J Anaesth 2018;
      120: 299-307.

PMID- 30236262
TI  - Stop before and after you block.

PMID- 30236258
TI  - Malignant hyperthermia, environmental heat stress, and intracellular calcium
      dysregulation in a mouse model expressing the p.G2435R variant of RYR1.
AB  - BACKGROUND: The human p.G2434R variant of the RYR1 gene is most frequently
      associated with malignant hyperthermia (MH) in the UK. We report the phenotype of
      a knock-in mouse that expresses the RYR1 variant p.G2435R, which is isogenetic
      with the human variant. METHODS: We observed the general phenotype; determined
      the sensitivity of myotubes to caffeine-, KCl, and halothane-induced Ca2+
      release; determined the in vivo response to halothane or increased ambient
      temperature; and determined the in vivo myoplasmic intracellular Ca2+
      concentration in skeletal muscle before and during exposure to volatile
      anaesthetics. RESULTS: RYR1 pG2435R/MH normal (MHS-Heterozygous[Het]) or RYR1
      pG2435R/pG2435R (MHS-Homozygous[Hom]) mice were fully viable under typical
      rearing conditions, although some male MHS-Hom mice died spontaneously. The
      normalised half-maximal effective concentration (95% confidence interval) for
      intracellular Ca2+ release in myotubes in response to KCl [MH normal, MHN, 21.4
      (19.8-23.1) mM; MHS-Het 16.2 (15.2-17.2) mM; MHS-Hom 11.2 (10.2-12.2) mM] and
      caffeine (MHN, 5.7 (5-6.3) mM; MHS-Het 4.5 (3.9-5.0) mM; MHS-Hom 1.77 (1.5-2.1)
      mM] exhibited a gene dose-dependent decrease, and there was a gene dose-dependent
      increase in halothane sensitivity. Intact animals show a gene dose-dependent
      susceptibility to MH with volatile anaesthetics or to heat stroke. RYR1 p.G2435R
      mice had elevated skeletal muscle intracellular resting [Ca2+]i, (values are
      expressed as mean (SD)) (MHN 123 (3) nM; MHS-Het 156 (16) nM; MHS-Hom 265 (32)
      nM; P<0.001) and [Na+]i (MHN 8 (0.1) mM; MHS-Het 10 (1) mM; MHS-Hom 14 (0.7) mM;
      P<0.001) that was further increased by exposure to volatile anaesthetics.
      CONCLUSIONS: RYR1 pG2435R mice demonstrated gene dose-dependent in vitro and in
      vivo responses to pharmacological and environmental stressors that parallel those
      seen in patients with the human RYR1 variant p.G2434R.

PMID- 30236263
TI  - Increase in regional oxygen saturation in the thigh indicates successful block of
      the femoral nerve after lumbar plexus block.

PMID- 30236264
TI  - Patient blood management in intracranial neurosurgery-do we have sufficient data
      to define a transfusion threshold? Comment on Br J Anaesth 2018; 120: 988-98.

PMID- 30236265
TI  - Response to: 'Patient blood management in intracranial neurosurgery-do we have
      sufficient data to define a transfusion threshold?' (Br J Anaesth 2018; 121: 974
      76).

PMID- 30236267
TI  - Novel use of ultrasound to reposition guidewire during internal jugular vein
      cannulation.

PMID- 30236266
TI  - The potential power and hidden hazards of Trial Sequential Analysis regarding
      viscoelastic blood tests in cardiac surgery. Comment on Br J Anaesth 2017; 118:
      823-33.

PMID- 30236268
TI  - Has malignant hyperthermia really disappeared with halothane? Comment on Br J
      Anaesth 2017; 119: i44-52.

PMID- 30236270
TI  - Time waits for no intensivist. Comment on Br J Anaesth 2018; 120: 1420-8.

PMID- 30236269
TI  - Impact of intensive care unit admission and discharge times on adverse outcomes
      after planned surgical cases. Response to Br J Anaesth 2018; 120: 1153-4.

PMID- 30236271
TI  - Punctuality is the duty of subjects and the politeness of monarchs. Response to
      Br J Anaesth 2018; 121: 982-3.

PMID- 30236272
TI  - Mad as a hatter? Evaluating doctors' recall of names in theatres and attitudes
      towards adopting #theatrecapchallenge.

PMID- 30236273
TI  - Comment on 'Association between intraoperative opioid administration and 30-day
      readmission: a pre-specified analysis of registry data from a healthcare network
      in New England' (Br J Anaesth 2018;120:1090-1102).

PMID- 30236274
TI  - Complications in aortic surgery: are CSF drains to be blamed? Comment on Br J
      Anaesth 2018; 120: 904-913.

PMID- 30236275
TI  - Pooled meta-analysis on cerebrospinal-fluid-drain-related complications. Response
      to Br J Anaesth 2018; 121: 987.

PMID- 30236277
TI  - The Multi-pronged Regulation of Adult Neurogenesis by Forkhead Box O Family
      Members.
AB  - In this issue of Neuron, Schaffner et al. (2018) discover multiple effects of the
      Forkhead Box O (FoxO) transcription factor family on the different stages of
      adult neurogenesis, including the genesis of dendrites and spines regulated by
      FoxO-dependent autophagic activity.

PMID- 30236276
TI  - Erratum to 'Nociceptive activation in spinal cord and brain persists during deep
      general anaesthesia' (Br J Anaesth 2018; 121: 291-302).

PMID- 30236279
TI  - The Enigmatic "Indirect Pathway" of the Basal Ganglia: A New Role.
AB  - Goal-directed behavior is processed in the dorsomedial striatum. Using a
      probabilistic reward paradigm, Nonomura et al. (2018) show that indirect pathway
      neurons signal when an action is incorrect and it is time to switch strategies,
      while the direct pathway remains active with a correct action.

PMID- 30236278
TI  - Peripheral Kappa Opioid Receptor Signaling Takes on a Central Role.
AB  - With the current unmet demand for effective analgesics and the opioid crisis,
      pain relief without major central adverse effects is highly appealing. In this
      issue of Neuron, Snyder et al. (2018) report on the localization, functions, and
      therapeutic potential of kappa opioid receptors in peripheral sensory neurons.

PMID- 30236281
TI  - The Value of Undergraduate Teaching for Research Scientists.
AB  - Teaching undergraduates is part of the academic commitment for many neuroscience
      faculty. While some scientists view this as a major distraction from research,
      teaching is of high value, both in training young scientists and for informing
      one's own scientific investigations.

PMID- 30236280
TI  - Resolving Memory Circuits with Layer-Dependent fMRI.
AB  - Memory encoding and retrieval require directional exchange of information between
      different areas in the medial temporal lobe. In this issue of Neuron, Koster et
      al. (2018) use high-resolution fMRI combined with state-of-the-art data analysis
      methods to trace the information flow in memory circuits in hippocampus and
      entorhinal cortex.

PMID- 30236282
TI  - A Cortical Pathogenic Theory of Parkinson's Disease.
AB  - In Parkinson's disease, the progressive neurodegeneration of nigrostriatal
      dopaminergic neurons in the substantia nigra pars compacta (SNc) is associated
      with classic motor features, which typically have a focal onset. Since a defined
      somatotopic arrangement in the SNc has not been recognized, this focal motor
      onset is unexplained and hardly justified by current pathogenic theories of
      bottom-up disease progression (Braak's hypothesis, prionopathy). Here we propose
      that corticostriatal activity may represent a critical somatotopic "stressor" for
      nigrostriatal terminals, ultimately driving retrograde nigrostriatal degeneration
      and leading to focal motor onset and progression of Parkinson's disease. As a
      pathogenic mechanism, corticostriatal activity may promote secretion of striatal
      extracellular alpha-synuclein, favoring its pathological aggregation at
      vulnerable dopaminergic synapses. A similar pathogenic process may occur at
      corticofugal projections to the medulla oblongata and other vulnerable
      structures, thereby contributing to the bottom-up progression of Lewy pathology.
      This cortical pathogenesis may co-exist with bottom-up mechanisms, adding an
      integrative top-down perspective to the quest for the factors that impinge upon
      the vulnerability of dopaminergic cells in the onset and progression of
      Parkinson's disease.

PMID- 30236285
TI  - Big-Loop Recurrence within the Hippocampal System Supports Integration of
      Information across Episodes.
AB  - Recent evidence challenges the widely held view that the hippocampus is
      specialized for episodic memory, by demonstrating that it also underpins the
      integration of information across experiences. Contemporary computational
      theories propose that these two contrasting functions can be accomplished by big
      loop recurrence, whereby the output of the system is recirculated back into the
      hippocampus. We use ultra-high-resolution fMRI to provide support for this
      hypothesis, by showing that retrieved information is presented as a new input on
      the superficial entorhinal cortex-driven by functional connectivity between the
      deep and superficial entorhinal layers. Further, the magnitude of this laminar
      connectivity correlated with inferential performance, demonstrating its
      importance for behavior. Our findings offer a novel perspective on information
      processing within the hippocampus and support a unifying framework in which the
      hippocampus captures higher-order structure across experiences, by creating a
      dynamic memory space from separate episodic codes for individual experiences.

PMID- 30236284
TI  - Kappa Opioid Receptor Distribution and Function in Primary Afferents.
AB  - Primary afferents are known to be inhibited by kappa opioid receptor (KOR)
      signaling. However, the specific types of somatosensory neurons that express KOR
      remain unclear. Here, using a newly developed KOR-cre knockin allele, viral
      tracing, single-cell RT-PCR, and ex vivo recordings, we show that KOR is
      expressed in several populations of primary afferents: a subset of peptidergic
      sensory neurons, as well as low-threshold mechanoreceptors that form lanceolate
      or circumferential endings around hair follicles. We find that KOR acts centrally
      to inhibit excitatory neurotransmission from KOR-cre afferents in laminae I and
      III, and this effect is likely due to KOR-mediated inhibition of Ca2+ influx,
      which we observed in sensory neurons from both mouse and human. In the periphery,
      KOR signaling inhibits neurogenic inflammation and nociceptor sensitization by
      inflammatory mediators. Finally, peripherally restricted KOR agonists selectively
      reduce pain and itch behaviors, as well as mechanical hypersensitivity associated
      with a surgical incision. These experiments provide a rationale for the use of
      peripherally restricted KOR agonists for therapeutic treatment.

PMID- 30236286
TI  - Differential Control of Axonal and Somatic Resting Potential by Voltage-Dependent
      Conductances in Cortical Layer 5 Pyramidal Neurons.

PMID- 30236283
TI  - Molecular Dynamics Simulation for All.
AB  - The impact of molecular dynamics (MD) simulations in molecular biology and drug
      discovery has expanded dramatically in recent years. These simulations capture
      the behavior of proteins and other biomolecules in full atomic detail and at very
      fine temporal resolution. Major improvements in simulation speed, accuracy, and
      accessibility, together with the proliferation of experimental structural data,
      have increased the appeal of biomolecular simulation to experimentalists-a trend
      particularly noticeable in, although certainly not limited to, neuroscience.
      Simulations have proven valuable in deciphering functional mechanisms of proteins
      and other biomolecules, in uncovering the structural basis for disease, and in
      the design and optimization of small molecules, peptides, and proteins. Here we
      describe, in practical terms, the types of information MD simulations can provide
      and the ways in which they typically motivate further experimental work.

PMID- 30236288
TI  - We are Simply a Part of a Long Rich History....

PMID- 30236287
TI  - The BDNF Val66Met Prodomain Disassembles Dendritic Spines Altering Fear
      Extinction Circuitry and Behavior.

PMID- 30236289
TI  - Vote, Vote, Vote!

PMID- 30236290
TI  - Response to Bradley Letter.

PMID- 30236291
TI  - Nationwide Strategy for Addressing the Opioid Health Crisis in the Emergency
      Department and Beyond.

PMID- 30236292
TI  - Updated Knowledge About the Diagnosis and Treatment of Sepsis and Septic Shock.

PMID- 30236293
TI  - Above, Beyond, and Over the Side Rails: Evaluating the New Memorial Emergency
      Department Fall-Risk-Assessment Tool.

PMID- 30236294
TI  - Clinical Practice Guideline: Suicide Risk Assessment.

PMID- 30236295
TI  - Patient Transfers and Handoffs.

PMID- 30236296
TI  - A Look Back.

PMID- 30236297
TI  - Ambulatory Infusion Pumps: Coming to an Emergency Department Near You.

PMID- 30236298
TI  - Essential oils: Options for the Older Adult.

PMID- 30236299
TI  - Preventing Liquid Nicotine Toxic Effects on Children.

PMID- 30236300
TI  - A Different Spin to Emergency Nursing: Spain, Part 1.

PMID- 30236302
TI  - Choosing Between Single Center and Multicenter Data Collection.

PMID- 30236301
TI  - Ultra-Rapid Reversal of Rocuronium-Induced Paralysis with Sugammadex in the
      Emergency Department.

PMID- 30236305
TI  - Mitral Annular Calcification: The Search for Safer Options.

PMID- 30236304
TI  - Open Atrial Transcatheter Mitral Valve Replacement in Patients With Mitral
      Annular Calcification.
AB  - BACKGROUND: Mitral valve replacement in the setting of severe mitral annular
      calcification remains a surgical challenge. Transcatheter mitral valve
      replacement (TMVR) using an aortic balloon-expandable transcatheter heart valve
      is emerging as a potential treatment option for high surgical risk patients.
      Transseptal, transapical, or transatrial access is not always feasible, so an
      understanding of alternative implantation techniques is important. OBJECTIVES:
      The authors sought to present a step-by-step description of a contemporary
      transatrial TMVR technique using balloon-expandable aortic transcatheter heart
      valves. This procedure has evolved over time to address valve migration, left
      ventricular outflow tract obstruction, and paravalvular leak. The authors present
      a refined technique that has been associated with the most reproducible outcomes.
      METHODS: A step-by-step description of the TMVR technique and outcomes of 8
      patients treated using this technique are described. Baseline patient clinical
      and echocardiographic characteristics and 30-day post-TMVR outcomes are
      presented. RESULTS: Eight patients underwent transatrial TMVR at a single
      institution. Five had previous cardiac surgery. Mean STS score was 8%. Technical
      success by MVARC (Mitral Valve Academic Research Consortium) criteria was 100%.
      There was zero in-hospital and 30-day mortality. Procedural success by MVARC
      criteria at 30 days was 100%. Paravalvular leak immediately post-implant was none
      or trace in 6 and mild in 1. CONCLUSIONS: The technique described is reproducible
      and was associated with favorable outcomes in this early experience. It
      represents a useful technique for the treatment of mitral valve disease in the
      setting of severe annular calcification. A structured and defined implantation
      technique is critical to investigators as this field evolves.

PMID- 30236307
TI  - Alcohol and Cardiac Structure: Less Is Better.

PMID- 30236306
TI  - Association Between Alcohol Intake and Cardiac Remodeling.
AB  - BACKGROUND: Alcohol-induced cardiotoxicity is incompletely understood.
      Specifically, the long-term impact of alcohol use on ventricular remodeling or
      dysfunction, its modulators, and effect thresholds among young adults remain
      controversial. OBJECTIVES: The authors sought to evaluate a potential
      relationship between alcohol intake and cardiac remodeling, assessed by
      echocardiography, over 20 years of follow-up. METHODS: Among the CARDIA (Coronary
      Artery Risk Development in Young Adults) study cohort, the authors studied all
      subjects without baseline heart disorders who provided adequate information on
      their drinking habits and underwent echocardiographic evaluation at years 5 and
      25 of the study. The echocardiographic outcomes were left ventricular (LV)
      ejection fraction, indexed LV end-diastolic volume and LV mass, and left atrial
      diameter. Participants were grouped according to their weighted-average weekly
      drinking habits. An additional analysis used the estimated cumulative alcohol
      consumption. Regression models and multivariable fractional polynomials were used
      to evaluate the association between alcohol consumption and the outcomes.
      RESULTS: Among the 2,368 participants, alcohol consumption was an independent
      predictor of higher indexed LV mass (p = 0.014) and indexed LV end-diastolic
      volume (p = 0.037), regardless of sex. No significant relationship between
      alcohol intake and LV ejection fraction was found. Drinking predominantly wine
      was associated with less cardiac remodeling and there was a nonsignificant trend
      for a harmful effect of binge drinking. CONCLUSIONS: After 20 years of follow-up,
      alcohol intake was associated with adverse cardiac remodeling, although it was
      not related with LV systolic dysfunction in this initially healthy young cohort.
      Our results also suggest that drinking predominantly wine associates with less
      deleterious findings in cardiac structure.

PMID- 30236308
TI  - Edoxaban Versus Warfarin in Latin American Patients With Atrial Fibrillation: The
      ENGAGE AF-TIMI 48 Trial.
AB  - BACKGROUND: There is limited information about the use of antithrombotic
      therapies and outcomes of Latin American (LatAm) subjects with atrial
      fibrillation. The global ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor
      Xa Next Generation Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48)
      trial compared the efficacy and safety of edoxaban versus warfarin over a median
      follow-up of 2.8 years. OBJECTIVES: The authors aimed to compare adjusted
      outcomes in Latin America versus outside Latin America and to compare outcomes
      stratified by anticoagulant treatment and region. METHODS: The authors analyzed
      clinical characteristics and outcomes, adjusted for baseline characteristics, the
      Human Development Index, and randomized treatment of 2,661 LatAm versus 18,444
      non-Latin American subjects (nLAS). RESULTS: When compared with nLAS, LatAm
      subjects had a similar overall risk for stroke. After multivariate adjustment,
      the risks of stroke/systemic embolism (hazard ratio [HR]: 1.19; 95% confidence
      interval (CI): 0.96 to 1.47; p = 0.11) and major bleeding (HR: 1.10; 95% CI: 0.89
      to 1.36; p = 0.39) were similar in LatAm and nLAS. LatAm subjects were at higher
      adjusted risk of death (HR: 1.48; 95% CI: 1.30 to 1.69; p < 0.001) and
      intracranial hemorrhage (ICH) (HR: 1.55; 95% CI: 1.00 to 2.41; p = 0.049). In
      both regions, when compared with warfarin, edoxaban reduced stroke/systemic
      embolism (HR: 0.64 and 0.91 in LatAm and nLAS, respectively), major bleeding (HR:
      0.71 and 0.82), and cardiovascular death (HR: 0.78 and 0.88), without evidence of
      regional heterogeneity (pint = 0.41, 0.50, and 0.70, respectively). There was a
      greater reduction in hemorrhagic stroke with edoxaban in LatAm (HR: 0.16) than in
      nLAS (HR: 0.64; pint = 0.037). CONCLUSIONS: After multivariable adjustment, LatAm
      subjects with atrial fibrillation had higher rates of intracranial hemorrhage and
      death than nLAS. Outcomes with higher-dose edoxaban versus warfarin were at least
      as favorable in LatAm subjects as in nLAS, with an even greater reduction in
      hemorrhagic stroke seen in LatAm.

PMID- 30236309
TI  - Edoxaban in Latin America.

PMID- 30236310
TI  - Long-Term Outcomes After Off-Pump Versus On-Pump Coronary Artery Bypass Grafting
      by Experienced Surgeons.
AB  - BACKGROUND: Long-term benefits of off-pump versus on-pump coronary artery bypass
      grafting (CABG) are controversial. OBJECTIVES: The authors sought to compare long
      term survival and morbidity after on-pump versus off-pump CABG. METHODS:
      Mandatory clinical and administrative registries from New Jersey Department of
      Health were linked to identify patients who underwent CABG between 2005 and 2011,
      by surgeons who had performed at least 100 off-pump or on-pump CABG operations.
      Survival, stroke, myocardial infarction, repeat revascularization, and new
      dialysis requirement were compared using Cox modeling, propensity scores, and
      instrumental variable analysis. Median follow-up was 6.8 years (range: 0 to 11.0
      years); last follow-up date was December 31, 2015. RESULTS: Among 42,570 CABG
      patients, 6,950 who underwent off-pump CABG and 15,295 who underwent on-pump CABG
      met study criteria. Off-pump CABG was associated with higher mortality (33.4% vs.
      29.6% at 10 years; hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 1.04 to
      1.18; p = 0.002) compared with on-pump CABG. Off-pump CABG was associated with a
      higher risk of incomplete revascularization (15.7% vs. 8.8%; p < 0.001), which
      was a predictor of late mortality (HR: 1.10; 95% CI: 1.03 to 1.17; p = 0.006);
      and higher rates of repeat revascularization (15.4% vs. 14.0% at 10 years; HR:
      1.17; 95% CI: 1.01 to 1.37; p = 0.048). There were no significant differences in
      the rate of stroke, myocardial infarction, or new dialysis. CONCLUSIONS: In this
      mandatory clinical registry, off-pump was associated with increased incomplete
      revascularization, repeat revascularization, and mortality at 10 years compared
      with on-pump CABG, suggesting that on-pump CABG may be the appropriate choice for
      most patients undergoing surgical revascularization.

PMID- 30236311
TI  - Is Off-Pump CABG Off Base?

PMID- 30236313
TI  - A Role for Extracellular Matrix in Atherosclerotic Plaque Erosion.

PMID- 30236314
TI  - Healthy Weight and Obesity Prevention: JACC Health Promotion Series.
AB  - Overweight and obesity have reached epidemic levels in the United States and
      worldwide, and this has contributed to substantial cardiovascular and other
      health risks. However, controversy exists concerning the causes of obesity and
      effective modalities for its prevention and treatment. There is also controversy
      related to the concept of metabolically healthy obesity phenotype, the "obesity
      paradox," and on the importance of fitness to protect individuals who are
      overweight or obese from cardiovascular diseases. In this state-of-the-art
      review, the authors focus on "healthy weight" with the emphasis on the
      pathophysiologic effects of weight gain on the cardiovascular system;
      mechanistic/triggering factors; and the role of preventive actions through
      personal, education/environment, and societal/authoritative factors, as well as
      factors to provide guidance for caregivers of health promotion. Additionally, the
      authors briefly review metabolically healthy obesity, the obesity paradox, and
      issues beyond lifestyle consideration for weight loss with medications and
      bariatric surgery.

PMID- 30236312
TI  - Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome: Implications for
      Plaque Erosion.
AB  - BACKGROUND: Superficial erosion currently causes at least one-third of acute
      coronary syndromes (ACS), and its incidence is increasing. Yet, the underlying
      mechanisms in humans are still largely unknown. OBJECTIVES: The authors sought to
      assess the role of hyaluronan (HA) metabolism in ACS. METHODS: Peripheral blood
      mononuclear cells were collected from ACS (n = 66), stable angina (SA) (n = 55),
      and control (CTRL) patients (n = 45). The authors evaluated: 1) gene expression
      of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its
      proinflammatory 20-kDa isoform) and of CD44v1, CD44v4, and CD44v6 splicing
      variants of HA receptor; and 2) HYAL2 and CD44 protein expression. Moreover, they
      compared HYAL2 and CD44 gene expression in ACS patients with plaque erosion
      (intact fibrous cap and thrombus) and in ACS patients with plaque rupture,
      identified by optical coherence tomography analysis. RESULTS: Gene expression of
      HYAL2, CD44v1, and CD44v6 were significantly higher in ACS as compared with SA (p
      = 0.003, p < 0.001, and p = 0.033, respectively) and CTRL subjects (p < 0.001, p
      < 0.001, and p = 0.009, respectively). HYAL2 protein expression was significantly
      higher in ACS than in SA (p = 0.017) and CTRL (p = 0.032), whereas no differences
      were found in CD44 protein expression. HYAL2 and CD44v6 gene expression was
      significantly higher in patients with plaque erosion than in those with plaque
      rupture (p = 0.015 and p = 0.029, respectively). CONCLUSIONS: HYAL2 and CD44v6
      splicing variants seem to play an important role in ACS, in particular when
      associated with plaque erosion. After further validation, HYAL2 might represent a
      potentially useful biomarker for the noninvasive identification of this mechanism
      of coronary instability.

PMID- 30236316
TI  - Overlap in Age at the Time of Elective Percutaneous Coronary Intervention and at
      Noncardiac Surgery.

PMID- 30236315
TI  - Positive Pressure Ventilation in the Cardiac Intensive Care Unit.
AB  - Contemporary cardiac intensive care units (CICUs) provide care for an aging and
      increasingly complex patient population. The medical complexity of this
      population is partly driven by an increased proportion of patients with
      respiratory failure needing noninvasive or invasive positive pressure ventilation
      (PPV). PPV often plays an important role in the management of patients with
      cardiogenic pulmonary edema, cardiogenic shock, or cardiac arrest, and those
      undergoing mechanical circulatory support. Noninvasive PPV, when appropriately
      applied to selected patients, may reduce the need for invasive mechanical PPV and
      improve survival. Invasive PPV can be lifesaving, but has both favorable and
      unfavorable interactions with left and right ventricular physiology and carries a
      risk of complications that influence CICU mortality. Effective implementation of
      PPV requires an understanding of the underlying cardiac and pulmonary
      pathophysiology. Cardiologists who practice in the CICU should be proficient with
      the indications, appropriate selection, potential cardiopulmonary interactions,
      and complications of PPV.

PMID- 30236317
TI  - Accelerated Left Ventricular Interstitial Collagen Deposition After Receiving
      Doxorubicin in Hypertension.

PMID- 30236318
TI  - Heart Failure With Recovered Ejection Fraction.

PMID- 30236319
TI  - Infective Endocarditis and Valve-Pathogen Predilection.

PMID- 30236320
TI  - Risk of Cardiovascular Disease Among Young Adults: Marijuana Use or the Company
      it Keeps.

PMID- 30236321
TI  - Cocaine and/or Marijuana Use and Myocardial Infarction.

PMID- 30236322
TI  - Reply: Cocaine, Tobacco, and Toxicology in Myocardial Infarction of the Young.

PMID- 30236323
TI  - Retraction notice to "Heat shock protein 27 expression is spatially distributed
      in human placenta and selectively regulated during preeclampsia." [JRI 101-102C
      (2014) 89 - 95.

PMID- 30236324
TI  - Adolescent With Chest Pain and Dyspnea.

PMID- 30236325
TI  - Agitation Crisis Control.

PMID- 30236326
TI  - Commentary.

PMID- 30236327
TI  - Child With Autism and a Limp.

PMID- 30236328
TI  - The Four Horsemen of the Emergency Department.

PMID- 30236329
TI  - Dialysis in Undocumented Patients: Death on the Doorstep of the Emergency
      Department: Answers to the May 2018 Journal Club Questions.

PMID- 30236330
TI  - The Successes and Challenges of Integrating Emergency Medicine With Critical Care
      Medicine.

PMID- 30236331
TI  - Can Successful Intubation Be Attributed to the Specific Use of Neuromuscular
      Agent?

PMID- 30236332
TI  - In reply.

PMID- 30236333
TI  - In reply.

PMID- 30236334
TI  - Man With Sudden Lower Leg Numbness.

PMID- 30236335
TI  - Young Boy With Lateral Foot Pain.

PMID- 30236336
TI  - Access to 911 Public Safety Centers, Emergency Medical Dispatch, and Public
      Emergency Aid Training.

PMID- 30236337
TI  - Appropriate Use Criteria for Handheld/Pocket Ultrasound Devices.

PMID- 30236338
TI  - Coverage for Patient Home Medication While Under Observation Status.

PMID- 30236339
TI  - Delivery of Care to Undocumented Persons.

PMID- 30236340
TI  - Disaster Medical Services.

PMID- 30236341
TI  - Emergency Physician Contractual Relationships.

PMID- 30236343
TI  - Guideline for Ultrasound Transducer Cleaning and Disinfection.

PMID- 30236342
TI  - Financing of Graduate Medical Education in Emergency Medicine.

PMID- 30236345
TI  - Interpretation of Diagnostic Imaging Tests.

PMID- 30236344
TI  - Impact of Climate Change on Public Health and Implications for Emergency
      Medicine.

PMID- 30236346
TI  - Interpretation of EMTALA in Medical Malpractice Litigation.

PMID- 30236347
TI  - Nondiscrimination and Harassment.

PMID- 30236348
TI  - Patient Autonomy and Destination Factors in Emergency Medical Services (EMS) and
      EMS-Affiliated Mobile Integrated Healthcare/Community Paramedicine Programs.

PMID- 30236349
TI  - Prescription Drug Pricing.

PMID- 30236350
TI  - Relationship Between Clinical Capabilities and Medical Equipment in the Practice
      of Emergency Medical Services Medicine.

PMID- 30236351
TI  - Resident Training for Practice in Nonurban/Underserved Areas.

PMID- 30236352
TI  - A Practical Approach to the Management of Complications During Percutaneous
      Coronary Intervention.
AB  - Percutaneous coronary intervention relieves symptoms in patients with chronic
      ischemic heart disease resistant to optimal medical therapy and alters the
      natural history of acute coronary syndromes. However, adverse procedural outcomes
      may occur during the intervention. Knowledge of possible complications and their
      timely management are essential for the practicing cardiologist and can be life
      saving for the patient. In this review, the authors summarize potential
      complications of percutaneous coronary intervention focusing on their practical
      management.

PMID- 30236354
TI  - Further Refinements to a System of Care for Out-of-Hospital Cardiac Arrest Bring
      Substantial Benefit: A Call to Action.

PMID- 30236353
TI  - Mortality in Patients With Out-of-Hospital Cardiac Arrest Undergoing a
      Standardized Protocol Including Therapeutic Hypothermia and Routine Coronary
      Angiography: Experience From the HACORE Registry.
AB  - OBJECTIVES: This study sought to analyze the impact of mandatory therapeutic
      hypothermia and cardiac catheterization in the absence of overt noncardiac cause
      of arrest as part of the Hannover Cardiac Resuscitation Algorithm before
      intensive care admission. BACKGROUND: Despite advanced therapies, out-of-hospital
      cardiac arrest (OHCA) is still associated with high mortality rates. Recently,
      the TTM (Target Temperature Management 33 degrees C Versus 36 degrees C After Out
      of-Hospital Cardiac Arrest)-trial caused severe uncertainty about the efficacy of
      and need for therapeutic hypothermia. Furthermore, the role of early coronary
      angiography in OHCA survivors without ST-segment elevation remains undetermined.
      METHODS: In the HACORE (HAnnover Cooling REgistry) we investigated 233
      consecutive patients (median age 64 [interquartile range: 53 to 74] years) with
      OHCA admitted to our institution between January 2011 and December 2015 who were
      treated according to the algorithm. RESULTS: A total of 73% had ventricular
      fibrillation as primary rhythm. Return of spontaneous circulation was achieved
      after 20 (interquartile range: 10 to 30) min. Immediate percutaneous coronary
      angiography was performed in 96% and coronary angioplasty in 59% of all cases. ST
      segment elevation was present in 47%. Critical coronary stenosis requiring
      percutaneous coronary intervention was present in 67% of patients with and 52% of
      patients without ST-segment elevation. Overall 30-day intrahospital mortality in
      this real-world registry was 37%. Patients in our local registry who matched the
      inclusion/exclusion criteria of the TTM-trial (n = 145) had a markedly lower 30
      day mortality (27%) compared with the published trial (44%). CONCLUSIONS:
      Standardized treatment of patients with OHCA following a strict protocol
      incorporating computed tomography, cardiac catheterization and revascularization,
      liberal use of active hemodynamic support in presence of shock, and mandatory
      therapeutic hypothermia results in mortality rates lower than previously
      reported.

PMID- 30236356
TI  - Systems for Rapid Revascularization in ST-Segment Elevation Myocardial Infarction
      With Cardiogenic Shock: An Important Yet Elusive Goal.

PMID- 30236355
TI  - Delays in Primary Percutaneous Coronary Intervention in ST-Segment Elevation
      Myocardial Infarction Patients Presenting With Cardiogenic Shock.
AB  - OBJECTIVES: This study sought to examine whether quality improvement initiatives
      across multiple ST-segment elevation myocardial infarction (STEMI) systems
      translated to faster first medical contact (FMC)-to-device times for patients
      presenting with cardiogenic shock (CS). BACKGROUND: There are limited data
      describing contemporary rates of achieving guideline-directed FMC-to-device times
      for STEMI patients with CS. METHODS: From 2012 to 2014, the American Heart
      Association Mission: Lifeline STEMI Systems Accelerator project established a
      protocol-guided approach to STEMI reperfusion systems in 484 U.S. hospitals. The
      study was stratified by CS versus no CS at presentation and performed Cochrane
      Armitage tests to evaluate trends of achieving FMC-to-device time targets. A
      multivariable logistic regression model assessed the association between
      achieving guideline-directed FMC-to-device times and mortality. RESULTS: Among
      23,785 STEMI patients, 1,993 (8.4%) experienced CS at presentation. For direct
      presenters, patients with CS were less likely to achieve the 90-min FMC-to-device
      time compared with no-CS patients (37% vs. 54%; p < 0.001). For transferred
      patients, CS patients were even less likely to reach the 120-min FMC-to-device
      time compared with no-CS patients (34% vs. 47%; p < 0.0001). The Accelerator
      intervention did not result in improvements in the FMC-to-device times for direct
      presenting CS patients (p for trend = 0.53), although there was an improvement
      for transferred patients (p for trend = 0.04). Direct-presenting patients
      arriving within 90 min had lower mortality rates compared with patients who
      reached after 90 min (20.49% vs. 39.12%; p < 0.001). CONCLUSIONS: Fewer than 40%
      of STEMI patients presenting with CS achieved guideline-directed FMC-to-device
      targets; delays in reperfusion for direct-presenting patients were associated
      with higher mortality.

PMID- 30236357
TI  - Association Between Cardiac Catheterization Laboratory Pre-Activation and
      Reperfusion Timing Metrics and Outcomes in Patients With ST-Segment Elevation
      Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A
      Report From the ACTION Registry.
AB  - OBJECTIVES: The aim of this study was to describe the prevalence of pre-hospital
      cardiac catheterization laboratory activation and its association with
      reperfusion timeliness and in-hospital mortality. BACKGROUND: For patients with
      ST-segment elevation myocardial infarction diagnosed in the field,
      catheterization laboratory pre-activation may lead to more timely reperfusion and
      improved outcomes. METHODS: A total of 27,840 patients with ST-segment elevation
      myocardial infarction transported via emergency medical services to 744
      percutaneous coronary intervention-capable hospitals in the ACTION Registry from
      January 2015 to March 2017 were evaluated, excluding patients with cardiac arrest
      or requiring pre-percutaneous coronary intervention intubation. Catheterization
      laboratory pre-activation was defined as activation >10 min prior to hospital
      arrival. RESULTS: Catheterization laboratory pre-activation occurred in 41% of
      patients (n = 11,379), with minor presenting differences between those with and
      without catheterization laboratory pre-activation. Compared with no
      catheterization laboratory pre-activation, pre-activation patients were more
      likely to be directly transported to the catheterization laboratory on hospital
      arrival (23.3% vs. 5.3%), to have shorter hospital arrival-to-catheterization
      laboratory arrival time (median 17 min [interquartile range (IQR): 7 to 25 min]
      vs. 28 min [IQR: 18 to 39 min]), to have shorter door-to-device time (40 min
      [IQR: 30 to 51 min] vs. 52 min [IQR: 41 to 65 min]), and to have a greater
      likelihood of achieving first medical contact-to-device time <=90 min (76.6% vs.
      68.6%) (p < 0.001 for all). Pre-activation was associated with lower in-hospital
      mortality (2.8% vs. 3.4%; p = 0.01). Patients treated at hospitals in the lowest
      tertile of pre-activation rates had higher mortality than those treated at
      hospitals in the highest tertile before and after adjustment (3.6% vs. 2.7%;
      adjusted odds ratio: 1.33; 95% confidence interval: 1.08 to 1.63). CONCLUSIONS:
      In the United States, catheterization laboratory pre-activation occurred in fewer
      than one-half of emergency medical services-transported patients with ST-segment
      elevation myocardial infarction. Its association with faster reperfusion and
      lower mortality supports greater use of this strategy.

PMID- 30236359
TI  - Coronary Physiology in the Nonculprit Vessel After Acute Myocardial Infarction:
      To Go With the Flow or Unexpected Resistance?

PMID- 30236360
TI  - Temporal Trends and Outcomes of Percutaneous Coronary Interventions in
      Nonagenarians: A National Perspective.
AB  - OBJECTIVES: This study sought to assess temporal trends and outcomes of
      percutaneous coronary intervention (PCI) in nonagenarians. BACKGROUND: With
      increasing life expectancy, nonagenarians requiring PCI are increasing even
      though outcomes data are limited. METHODS: The National Inpatient Sample was used
      to identify all hospitalizations for PCI in patients aged >=90 years from January
      1, 2003, to December 31, 2014. The primary outcome was in-hospital mortality.
      RESULTS: Nonagenarians (n = 69,271) constituted 0.9% of all PCI hospitalizations,
      increasing from 0.6% in 2003 to 2004 to 1.4% in 2013 to 2014 (ptrend < 0.001).
      From 2003-2004 to 2013-2014, the proportion of PCIs performed for ST-segment
      elevation myocardial infarction (STEMI) (23.1% to 30.9%) and non-ST-segment
      elevation acute coronary syndromes (49.6% to 52.6%) increased, whereas those for
      stable ischemic heart disease (SIHD) decreased (27.3% to 16.5%), respectively
      (ptrend < 0.001 for all). Overall in-hospital mortality after PCI for STEMI, non
      ST-segment elevation acute coronary syndromes, and SIHD were 16.4%, 4.2%, and
      1.8%, respectively. After multivariable risk adjustment for demographics,
      comorbidities, and hospital-level characteristics, in-hospital mortality remained
      unchanged in STEMI (odds ratio: 1.04; 95% confidence interval: 0.98 to 1.11;
      ptrend = 0.20) and non-ST-segment elevation acute coronary syndromes (odds ratio:
      0.99; 95% confidence interval: 0.91 to 1.08; ptrend = 0.82), but increased in
      SIHD (odds ratio: 1.21; 95% confidence interval: 1.01 to 1.44; ptrend = 0.04)
      from 2003 to 2004 to 2013 to 2014. The rates of bleeding and vascular
      complications decreased or remained stable in all 3 subgroups, whereas risk
      adjusted incidence of stroke increased in patients with STEMI or SIHD.
      CONCLUSIONS: The rate of in-hospital mortality, major bleeding, vascular
      complications, and stroke after PCI in nonagenarians changed significantly from
      2003 to 2014. This study provides a benchmark for discussion of PCI-related risks
      among physicians, patients, and families.

PMID- 30236358
TI  - Fractional Flow Reserve and Instantaneous Wave-Free Ratio for Nonculprit Stenosis
      in Patients With Acute Myocardial Infarction.
AB  - OBJECTIVES: The aim of this study was to compare the changes of fractional flow
      reserve (FFR) or instantaneous wave-free ratio (iFR) with severity of epicardial
      coronary stenosis between nonculprit vessel of acute myocardial infarction (AMI)
      and stable ischemic heart disease (SIHD). BACKGROUND: There has been debate
      regarding the reliability of FFR or iFR for nonculprit stenosis in the acute
      stage of AMI. METHODS: A total of 100 AMI patients underwent comprehensive
      physiologic assessment including FFR, iFR, coronary flow reserve (CFR), and index
      of microcirculatory resistance (IMR) for nonculprit vessel stenosis after primary
      percutaneous coronary intervention (PCI) for culprit vessel. The changes in FFR
      and iFR for diameter stenosis (%DS) of nonculprit vessel stenosis were compared
      with FFR and iFR measured in 203 patients with SIHD. RESULTS: From 40% to 80%
      stenosis, FFR and iFR measured in nonculprit vessel of AMI patient showed
      significant decrease with worsening stenosis severity (all p values < 0.001).
      Nonculprit vessels of AMI patients showed lower CFR than SIHD; however, IMR was
      not different between the nonculprit vessel of AMI and SIHD patients. FFR and iFR
      were not significantly different between the nonculprit vessel of AMI and SIHD
      patients in all %DS groups from 40% to 80% (all p values > 0.05). In addition,
      percent difference of FFR and iFR according to the increase in %DS was also not
      significantly different between nonculprit vessel of AMI or SIHD. There was no
      significant interaction between clinical presentation and the changes of FFR and
      iFR for worsening %DS (interaction p value = 0.698 and 0.257, respectively).
      CONCLUSIONS: Changes in FFR and iFR for the nonculprit stenosis of AMI patients
      were not significantly different from those in SIHD patients. These data support
      the use of invasive physiological parameters to guide treatment of nonculprit
      stenoses in the acute stage of successfully revascularized AMI.

PMID- 30236361
TI  - Chronological Age Is Just a Number When it Comes to Percutaneous Coronary
      Intervention: Why Frailty May Matter More.

PMID- 30236362
TI  - Nonroutine Use of Intra-Aortic Balloon Pump in Cardiogenic Shock Complicating
      Myocardial Infarction With Successful and Unsuccessful Primary Percutaneous
      Coronary Intervention.
AB  - OBJECTIVES: The authors sought to compare outcomes of patients with myocardial
      infarction and cardiogenic shock (CS) treated with percutaneous coronary
      intervention (PCI) with or without intra-aortic balloon pump (IABP) support
      according to final epicardial flow in the infarct-related artery. BACKGROUND: A
      routine use of IABP is contraindicated in patients with myocardial infarction and
      CS. There are no data regarding the subpopulation of patients who may benefit
      from such support besides patients with mechanical complications of myocardial
      infarction. METHODS: Prospective nationwide registry data of patients with
      myocardial infarction and CS treated with PCI between 2003 and 2014 were
      analyzed. Patients were initially stratified into 2 groups according to final
      infarct-related artery Thrombolysis In Myocardial Infarction (TIMI) flow grade
      after PCI: those with successful primary PCI (TIMI flow grades 2 or 3) and those
      with unsuccessful primary PCI (TIMI flow grades 0 or 1). Outcomes of patients
      with or without IABP treatment in each group were analyzed and compared. RESULTS:
      In the unsuccessful PCI group, patients in whom IABP was applied had lower in
      hospital, 30-day, and 12-month mortality. IABP support in this group of patients
      was an independent predictor of lower 30-day mortality (hazard ratio [HR]: 0.72;
      95% confidence interval [CI]: 0.59 to 0.89; p = 0.002). Conversely, in patients
      with successful PCI, IABP was an independent predictor of higher 30-day mortality
      (HR: 1.18; 95% CI: 1.08 to 1.30; p = 0.0004). CONCLUSIONS: IABP is associated
      with a lower risk of 30-day mortality in patients with myocardial infarction
      complicated by CS, in whom primary PCI was unsuccessful.

PMID- 30236364
TI  - Instantaneous Wave-Free Ratio and Resting Pd/Pa in Tandem Lesions.

PMID- 30236363
TI  - Intra-Aortic Balloon Pumping: In Search of the Last Remaining Indication?

PMID- 30236366
TI  - Reply: Clinical Sequelae of Leaflet Thrombosis Following Transcatheter Aortic
      Valve Replacement at Medium-Term Follow-Up.

PMID- 30236365
TI  - Differences Between Fractional Flow Reserve and Instantaneous Wave-Free Ratio
      Clarified by Consideration of a Mathematical Model of Diffuse Coronary Stenosis.

PMID- 30236367
TI  - Clinical Sequelae of Leaflet Thrombosis Following Transcatheter Aortic Valve
      Replacement at Medium-Term Follow-Up.

PMID- 30236368
TI  - Coronary Artery Fenestration: A Promising Technique for Rescue Management of
      Spontaneous Intramural Hematoma With Luminal Compression.

PMID- 30236369
TI  - Catch-up human papillomavirus vaccination: don't throw the baby out with the
      bathwater.

PMID- 30236370
TI  - Precious time to respond to infantile spasms.

PMID- 30236371
TI  - Prediabetes in youth: an opportunity to make a difference.

PMID- 30236372
TI  - Fetal life shapes adult male reproductive function.

PMID- 30236373
TI  - How should health service researchers respect children's personal data under
      GDPR?

PMID- 30236375
TI  - Healing through play.

PMID- 30236374
TI  - Adolescent health and wellbeing: advocating a role for urban design.

PMID- 30236376
TI  - Oxford Young Adult Clinic.

PMID- 30236377
TI  - Artists adopt orphan diseases.

PMID- 30236378
TI  - Seeing the material world through a child's eyes.

PMID- 30236379
TI  - Effectiveness of catch-up human papillomavirus vaccination on incident cervical
      neoplasia in a US health-care setting: a population-based case-control study.
AB  - BACKGROUND: The population effectiveness of human papillomavirus (HPV) catch-up
      vaccination, defined in the USA as first vaccination at ages 13-26 years, has not
      been studied extensively. We aimed to assess the risk of cervical intraepithelial
      neoplasia (CIN) 2, CIN3, adenocarcinoma in situ, or cancer (CIN2+ and CIN3+) by
      prior HPV vaccination status, age at first dose, and number of doses in women
      participating in a screening programme within a large integrated health-care
      system. METHODS: We performed a nested case-control study of women enrolled in
      Kaiser Permanente Northern California (an integrated health-care delivery system
      in California, USA). Cases were women with CIN2+ or CIN3+ confirmed by histology
      between Jan 1, 1995, and June 30, 2014, and incidence density-selected controls
      were age-matched women without CIN2+ or CIN3+ at the time each case occurred. For
      each case, we randomly selected five controls. Cases and controls were aged 26
      years or younger when the HPV quadrivalent vaccine became available in 2006. Rate
      ratios (RRs) from conditional logistic regression were estimated by age at time
      of first HPV quadrivalent vaccine dose (14-17 years, 18-20 years, and >=21
      years), and number of doses (one, two, and three or more doses) compared with no
      prior vaccination, with adjustment for smoking, hormonal contraceptive
      prescription, race or ethnicity, sexually transmitted infections,
      immunosuppression, parity, and number of outpatient visits. FINDINGS: 4357
      incident CIN2+ cases and 21 773 matched controls were included in the study. Of
      these, 1849 were incident CIN3+ cases with 9242 matched controls. The youngest
      age at time of first vaccination was 14 years. One or more HPV vaccine doses
      conferred protection against CIN2+ (RR 0.82, 95% CI 0.73-0.93) and CIN3+ (0.77,
      0.64-0.94). We found the strongest protection against CIN2+ in women who had
      received at least three vaccine doses and had received their first dose aged 14
      17 years (0.52, 0.36-0.74) or aged 18-20 years (0.65, 0.49-0.88). No significant
      protection was found in women aged 21 years or older at time of first dose (0.94,
      0.81-1.09). Inferences were similar for CIN3+, but with stronger effects for
      women who received at least three vaccine doses and had received their first dose
      aged 14-17 years (0.27, 0.13-0.56) or aged 18-20 years (0.59, 0.36-0.97).
      INTERPRETATION: Catch-up quadrivalent HPV vaccination with three doses was
      effective against CIN2+ and CIN3+ in girls and women aged 14-20 years at time of
      first vaccine dose but not for women aged 21 years and older at first dose.
      FUNDING: US National Cancer Institute.

PMID- 30236382
TI  - Association between male genital anomalies and adult male reproductive disorders:
      a population-based data linkage study spanning more than 40 years.
AB  - BACKGROUND: The male genital anomalies hypospadias and undescended testes have
      been linked to adult male reproductive disorders, testicular cancer, and
      decreased fertility. Few population-based studies have evaluated their effects on
      adult fertility outcomes and, in the case of undescended testes, the importance
      of early corrective surgery (orchidopexy). METHODS: We did a population-based
      cohort study of all liveborn boys in Western Australia in 1970-99, and followed
      them up until 2016 via data linkage to registries for hospital admissions,
      congenital anomalies, cancer, and assisted reproductive technologies (ART). Study
      factors were hypospadias or undescended testes, and study outcomes were
      testicular cancer, paternity, and use of ART for male infertility. Cox regression
      was used to calculate hazard ratios (HRs) for the associations between genital
      anomalies and testicular cancer or paternity, and log-binomial regression was
      used to calculate relative risks (RRs) for the associations between genital
      anomalies and use of ART. FINDINGS: The cohort comprised 350 835 boys, of whom
      2484 (0.7%) had been diagnosed with hypospadias and 7499 (2.1%) with undescended
      testes. There were 505 (0.1%) cases of testicular cancer, 109 471 (31.2%) men had
      fathered children, and 2682 (0.8%) had undergone fertility treatment with ART.
      Undescended testes was associated with a more than two times increase in risk of
      testicular cancer (HR 2.43, 95% CI 1.65-3.58) and hypospadias with an almost 40%
      increase (1.37, 0.51-3.67), although this increase was not significant. Both
      hypospadias and undescended testes were associated with a 21% reduction in
      paternity (adjusted HR 0.79 [95% CI 0.71-0.89] for hypospadias and 0.79 [0.74
      0.85] for undescended testes). Undescended testes was associated with a two times
      increase in use of ART (adjusted RR 2.26, 95% CI 1.58-3.25). For every 6 months'
      delay in orchidopexy, there was a 6% increase in risk of testicular cancer (HR
      1.06, 95% CI 1.03-1.08), a 5% increase in risk of future use of ART (1.05, 1.03
      1.08), and a 1% reduction in paternity (RR 0.99, 95% CI 0.98-0.99).
      INTERPRETATION: Undescended testes is associated with an increased risk of
      testicular cancer and male infertility, and decreased paternity. We provide new
      evidence to support current guidelines for orchidopexy before age 18 months to
      decrease the risk of future testicular cancer and infertility. FUNDING: National
      Health and Medical Research Council and Sydney Medical School Foundation.

PMID- 30236381
TI  - Trajectories of changes in glucose tolerance in a multiethnic cohort of obese
      youths: an observational prospective analysis.
AB  - BACKGROUND: Type 2 diabetes is preceded by a prediabetic stage of impaired
      glucose tolerance that affects 10-23% of youth and is expected to double over the
      next decade. The natural history of impaired glucose tolerance and the
      determinants of beta-cell dynamic response have never been investigated
      longitudinally in young people. We aimed to investigate the clinical and
      metabolic determinants of longitudinal glucose tolerance changes and beta-cell
      function in a multiethnic cohort of obese youth. METHODS: We followed up
      prospectively a multiethnic cohort of overweight and obese (body-mass index >85th
      percentile) adolescents with baseline normal glucose tolerance (plasma glucose
      <140 mg/dL) or impaired glucose tolerance (plasma glucose 140-199 mg/dL) at the
      Yale Pediatric Obesity Clinic (CT, USA). All participants underwent a 3-h oral
      glucose tolerance test at baseline and after 2 years to estimate insulin
      secretion (oral disposition index) in the context of body insulin sensitivity. As
      part of standard care at the clinic, all participants received dietary advice and
      underwent dietary assessment every 5-6 months. No structured lifestyle or
      pharmacological intervention was administered. FINDINGS: Between January, 2010,
      and December, 2016, 526 adolescents (mean age 12.7 years, range 10.6-14.2) were
      enrolled to our study. At baseline, 364 had normal and 162 had impaired glucose
      tolerance. Median follow-up was 2.9 years (IQR 2.7-3.1). 105 (65%) of 162 with
      impaired glucose tolerance at baseline reverted to normal glucose tolerance at
      follow-up, 44 (27%) had persistent impaired glucose tolerance, and 13 (8%)
      progressed to type 2 diabetes. A feature of reversion to normal glucose tolerance
      was a roughly four-fold increase in the oral disposition index (from median 0.94
      [IQR 0.68-1.35] at baseline to 3.90 [2.58-6.08] at follow-up; p<0.0001) and a
      significantly higher oral disposition index at follow-up compared with
      participants who maintained normal glucose tolerance across the study period
      (median 3.90 [IQR 2.58-6.08] vs 1.59 [1.12-2.23]; p<0.0001). By contrast, a
      decrease in insulin secretion was seen in participants who had persistent
      impaired glucose tolerance (median 1.31 [IQR 1.01-1.85]; p<0.0001) or who
      progressed to type 2 diabetes (0.20 [0.12-0.58]; p<0.0001), compared with
      participants who maintained normal glucose tolerance across the study period. Non
      Hispanic white ethnic origin conferred five times the odds of reversion to normal
      glucose tolerance compared with non-Hispanic black ethnic origin (OR 5.06, 95% CI
      1.86-13.76; p=0.001), with a two times greater annual increase in the oral
      disposition index (beta 2.32, 95% CI 0.05-4.60; p=0.045). INTERPRETATION:
      Impaired glucose tolerance is highly reversible in obese adolescents. Ethnic
      origin is the main clinical modifier of the dynamic beta-cell response to
      prediabetic hyperglycaemia and, thus, determines the reversibility of impaired
      glucose tolerance, or its persistence. Therapeutic interventions for impaired
      glucose tolerance should target the specific mechanisms underpinning glucose
      tolerance changes in high-risk ethnic groups. FUNDING: National Institutes of
      Health (National Institute of Child Health and Human Development, National Center
      for Research Resources, and National Institute of Diabetes and Digestive and
      Kidney Diseases), American Diabetes Association, International Society for
      Pediatric and Adolescent Diabetes, Robert Leet Patterson and Clara Guthrie
      Patterson Trust, European Society for Pediatric Endocrinology, American Heart
      Association, and the Allen Foundation.

PMID- 30236383
TI  - Peripheral neuropathy in children and adolescents treated for cancer.
AB  - Peripheral neuropathy is a well recognised treatment-related toxicity in children
      with cancer, associated with exposure to neurotoxic chemotherapy agents. Acute
      damage can occur in sensory, motor, or autonomic neurons, with symptoms that are
      rarely life threatening, but often severe enough to interfere with function
      during therapy and after treatment ends. The type of neuropathy and specific
      symptoms are associated with multiple factors including age at time of therapy,
      genetic predisposition, chemotherapy type and cumulative dose, and exposure to
      other agents during therapy. In this Review, we describe the peripheral
      neuropathy phenotype in children during cancer therapy and among survivors who
      have completed therapy, to summarise genetic and treatment-related risk factors
      for neuropathy, and to outline strategies to monitor and detect neuropathy during
      and after therapy. Additionally, we outline strategies for medical management of
      neuropathy during treatment and potential rehabilitation interventions to prevent
      or remediate functional loss.

PMID- 30236384
TI  - Intrauterine growth restriction and development of the hippocampus: implications
      for learning and memory in children and adolescents.
AB  - Intrauterine growth restriction (IUGR) is often the result of compromised
      placental function and suboptimal uteroplacental blood flow. Children born with
      IUGR have impaired cognitive functioning and specific memory deficits, indicating
      long-lasting impairments in hippocampal functioning; indeed, hippocampal volume
      is reduced in infants with IUGR. Animal studies have provided valuable insight
      into the nature of deficits in hippocampal-dependent functions observed in
      children born with IUGR; outcomes of experimental IUGR reveal reduced neuron
      numbers and morphological alterations in the cornu ammonis fields 1 and 3 and
      dentate gyrus subregions of the hippocampus. However, whether such early and
      ongoing structural changes in the hippocampus could account for deficits in
      spatial memory reported in adolescent rats with IUGR is yet to be established.
      Understanding the association between hippocampal structural and functional
      alterations in IUGR will aid in the development of interventions to minimise the
      effect of IUGR on the hippocampus and long-term cognitive outcomes.

PMID- 30236385
TI  - Ventricular Tachycardia Ablation in Nonischemic Cardiomyopathy.
AB  - Catheter ablation is being increasingly performed as adjunctive treatment to
      prevent recurrent implantable cardioverter-defibrillator therapies in patients
      with nonischemic cardiomyopathy and ventricular tachycardia (VT). In the context
      of VT ablation, nonischemic cardiomyopathy usually refers to dilated
      cardiomyopathy (DCM) as one morphological phenotype. Over the past decades,
      progress has been made to better characterize distinct subtypes and to
      differentiate between causes of DCM, which has important practical and prognostic
      implications. The goal of this review is to summarize available data on VT
      ablation in patients with DCM and, more specifically, review procedural and
      outcome data in specific etiologies and substrate location. It will focus on our
      current understanding of nonischemic scars, as well as the value of multimodal
      imaging, image integration, and electroanatomic mapping for substrate
      identification, procedural planning, and ablation. In addition, recent findings
      from whole human heart histology of patients with DCM and VT and their potential
      implications for imaging and mapping will be discussed.

PMID- 30236387
TI  - Catheter Ablation of Ventricular Tachycardia in Nonischemic Cardiomyopathy: The
      Relevance of Pathology Subtype and Experience of Centers: The More the Better?

PMID- 30236380
TI  - Vigabatrin with hormonal treatment versus hormonal treatment alone (ICISS) for
      infantile spasms: 18-month outcomes of an open-label, randomised controlled
      trial.
AB  - BACKGROUND: Infantile spasms constitute a severe form of epileptic
      encephalopathy. In the International Collaborative Infantile Spasms Study
      (ICISS), we showed that combining vigabatrin with hormonal therapy was more
      effective than hormonal therapy alone at stopping spasms between days 14 and 42
      of treatment. In this planned follow-up, we aimed to assess whether combination
      therapy was associated with improved developmental and epilepsy outcomes at 18
      months of age. METHODS: In ICISS, a multicentre, open-label, randomised
      controlled trial, infants were enrolled from 102 hospitals (three in Australia,
      11 in Germany, two in New Zealand, three in Switzerland, and 83 in the UK).
      Eligible infants had a clinical diagnosis of infantile spasms and a
      hypsarrhythmic (or similar) electroencephalogram (EEG) no more than 7 days before
      enrolment. Participants were randomly assigned (1:1) by a secure website to
      receive hormonal therapy with vigabatrin or hormonal therapy alone. If parents
      consented, there was an additional randomisation (1:1) of type of hormonal
      therapy used (prednisolone or tetracosactide depot). Block randomisation was
      stratified for hormonal treatment and risk of developmental impairment. Parents
      and clinicians were not masked to therapy, but investigators assessing epilepsy
      and developmental outcomes at 18 months were masked to treatment allocation.
      Minimum doses were oral prednisolone 10 mg four times a day or intramuscular
      tetracosactide depot 0.5 mg (40 IU) on alternate days with or without oral
      vigabatrin 100 mg/kg per day. The primary outcome at 18 months was development as
      assessed by the Vineland Adaptive Behaviour Scales (VABS) composite score.
      Secondary outcomes were the presence or absence of epileptic seizures or
      infantile spasms in the previous 28 days, as recorded by parents and carers, and
      the use of any anti-epileptic treatment (including ketogenic diet) in the
      previous 28 days. Analysis was by intention to treat. The trial is registered
      with the ISRCTN registry, number 54363174, and EudraCT, number 2006-000788-27.
      FINDINGS: Between March 7, 2007, and May 22, 2014, 766 infants were screened and,
      of those, 377 were randomly assigned to hormonal therapy with vigabatrin (n=186)
      or hormonal therapy alone (n=191). 362 infants were assessed for developmental
      and epilepsy outcomes at 18 months, 181 in each treatment group. Mean VABS scores
      did not differ significantly between the combination therapy group and the
      hormonal therapy alone group (73.9 [SE 1.3] vs 72.7 [1.4], difference -1.2 [95%
      CI -4.9 to 2.6], p=0.55). Presence of epilepsy at the assessment at age 18 months
      was similar in both treatment groups (54 [30.0%] of 180 infants who received
      combination therapy vs 52 [29.2%] of 178 who received hormonal therapy alone;
      difference 0.8% [95% CI -8.8 to 10.4], p=0.90). Presence of spasms was also
      similar in both treatment groups (27 [15.0%] of 180 infants on combination
      therapy vs 28 [15.7%] of 178 on hormonal therapy alone; difference 0.7% [95% CI 
      6.9 to 8.3], p=0.85). At the 18-month assessment, 158 (44.1%) of 358 infants were
      on some form of anti-epileptic treatment. Initial control of spasms between days
      14 and 42 of treatment was associated with higher mean VABS scores at 18 months
      (79.1 [SE 1.2] vs 63.2 [1.1], difference 15.9 [95% CI 12.4 to 19.5], p<0.001) and
      with higher likelihood of absence of seizures at 18 months (in 39 [17.0%] of 229
      infants who achieved spasm cessation vs 67 [51.9%] of 129 who did not; difference
      34.9% [24.8 to 45.0], p<0.001). Increasing lead-time to treatment was associated
      with lower VABS scores (analysis of variance: F[4,354]=6.38, p<0.001) and worse
      epilepsy outcomes (p=0.023). INTERPRETATION: Combination therapy did not result
      in improved developmental or epilepsy outcomes at 18 months. However, early
      clinical response to treatment was associated with improved developmental and
      epilepsy outcomes at 18 months. Longer lead-time to treatment was associated with
      poorer outcomes. Rapid diagnosis and effective treatment of infantile spasms
      could therefore improve outcomes. FUNDING: The Castang Foundation, Bath Unit for
      Research in Paediatrics, National Institute of Health Research, the Royal United
      Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach,
      University Children's Hospital Zurich.

PMID- 30236388
TI  - Importance of the Interventricular Septum as Part of the Ventricular Tachycardia
      Substrate in Nonischemic Cardiomyopathy.
AB  - OBJECTIVES: This study sought to characterize septal substrate in patients with
      nonischemic left ventricular cardiomyopathy (NILVCM) undergoing ventricular
      tachycardia (VT) ablation. BACKGROUND: The interventricular septum is an
      important site of VT substrate in NILVCM. METHODS: The authors studied 95
      patients with NILVCM and VT. Electroanatomic mapping using standard bipolar (<1.5
      mV) and unipolar (<8.3 mV) low-voltage criteria identified septal scar location
      and size. Analysis of unipolar voltage was performed and scars quantified using
      graded unipolar cutoffs from 4 to 8.3 mV were correlated with delayed gadolinium
      enhanced cardiac magnetic resonance (DE-CMR), performed in 57 patients. RESULTS:
      Detailed LV endocardial mapping (mean 262 +/- 138 points) showed septal bipolar
      and unipolar voltage abnormalities (VAs) in 44 (46%) and 79 (83%) patients, most
      commonly with basal anteroseptal involvement. Of the 59 patients in whom the
      septum was targeted, bipolar and unipolar septal VAs were seen in 36 (61%) and 54
      (92%). Of the 35 with CMR-defined septal scar, bipolar and unipolar septal VAs
      were seen in 18 (51%) and 31 (89%). In 12 patients without CMR septal scar, 6
      (50%) had isolated unipolar septal VAs on electroanatomic mapping, a subset of
      whom the septum was targeted for ablation (44%). In the graded unipolar analysis,
      the optimal cutoff associated with magnetic resonance imaging septal scar was 4.8
      mV (sensitivity 75%, specificity 70%; area under the curve: 0.75; 95% confidence
      interval: 0.60 to 0.90). CONCLUSIONS: Septal substrate by unipolar or bipolar
      voltage mapping in patients with NILVCM and VT is common. A unipolar voltage
      cutoff of 4.8 mV provides the best correlation with DE-CMR. A subset of patients
      with septal VT had normal DE-CMR or endocardial bipolar voltage with abnormal
      unipolar voltage.

PMID- 30236389
TI  - Characterization of Septal Scars in Nonischemic Left Ventricular Cardiomyopathy
      by Cardiac Magnetic Resonance Imaging Versus Electroanatomical Mapping: Superior,
      Inferior, or Complementary?

PMID- 30236386
TI  - Outcomes of Catheter Ablation of Ventricular Tachycardia Based on Etiology in
      Nonischemic Heart Disease: An International Ventricular Tachycardia Ablation
      Center Collaborative Study.
AB  - OBJECTIVES: This study sought to characterize ventricular tachycardia (VT)
      ablation outcomes across nonischemic cardiomyopathy (NICM) etiologies and adjust
      these outcomes by patient-related comorbidities that could explain differences in
      arrhythmia recurrence rates. BACKGROUND: Outcomes of catheter ablation of VT in
      patients with NICM could be related to etiology of NICM. METHODS: Data from 2,075
      patients with structural heart disease referred for catheter ablation of VT from
      12 international centers was retrospectively analyzed. Patient characteristics
      and outcomes were noted for the 6 most common NICM etiologies. Multivariable Cox
      proportional hazards modeling was used to adjust for potential confounders.
      RESULTS: Of 780 NICM patients (57 +/- 14 years of age, 18% women, left
      ventricular ejection fraction 37 +/- 13%), underlying prevalence was 66% for
      dilated idiopathic cardiomyopathy (DICM), 13% for arrhythmogenic right
      ventricular cardiomyopathy (ARVC), 6% for valvular cardiomyopathy, 6% for
      myocarditis, 4% for hypertrophic cardiomyopathy, and 3% for sarcoidosis. One-year
      freedom from VT was 69%, and freedom from VT, heart transplantation, and death
      was 62%. On unadjusted competing risk analysis, VT ablation in ARVC demonstrated
      superior VT-free survival (82%) versus DICM (p <= 0.01). Valvular cardiomyopathy
      had the poorest unadjusted VT-free survival, at 47% (p < 0.01). After adjusting
      for comorbidities, including age, heart failure severity, ejection fraction,
      prior ablation, and antiarrhythmic medication use, myocarditis, ARVC, and DICM
      demonstrated similar outcomes, whereas hypertrophic cardiomyopathy, valvular
      cardiomyopathy, and sarcoidosis had the highest risk of VT recurrence.
      CONCLUSIONS: Catheter ablation of VT in NICM is effective. Etiology of NICM is a
      significant predictor of outcomes, with ARVC, myocarditis, and DICM having
      similar but superior outcomes to hypertrophic cardiomyopathy, valvular
      cardiomyopathy, and sarcoidosis, after adjusting for potential covariates.

PMID- 30236392
TI  - Ventricular Tachycardia Ablation With Half-Normal Saline Irrigant: Half Is the
      New Normal?

PMID- 30236391
TI  - Prospective Multicenter Experience With Cooled Radiofrequency Ablation Using High
      Impedance Irrigant to Target Deep Myocardial Substrate Refractory to Standard
      Ablation.
AB  - OBJECTIVES: This study sought to evaluate the efficacy and safety of using half
      normal saline (HNS) as the cooling radiofrequency ablation (RFA) irrigant among
      patients who had failed prior, standard RFA. BACKGROUND: Effective control of
      ventricular arrhythmias that arise from mid-myocardium may be refractory to
      standard RFA. Recent data suggest that delivering fluid with decreased ionic
      concentration during open-irrigated RFA can produce deeper RFA lesions. METHODS:
      A 12-center prospective analysis was performed of all ablations using HNS for the
      treatment of ventricular arrhythmias (premature ventricular complex
      [PVC]/ventricular tachycardia [VT]) refractory to standard ablation with normal
      saline irrigant. RESULTS: HNS RFA was used clinically to target 94 PVC/VTs
      refractory to standard ablation. Acute success was achieved in 78 of 94 (83%),
      with longer-term success occurring in 78 subjects after a mean follow-up of 6.1
      +/- 6.7 months (range, 3.0 to 25.2 months). Steam pops were observed among 12
      (12.6%) patients. There were no significant changes in electrolytes measured
      before and after the use of HNS, and there were no complications related to HNS
      use. CONCLUSIONS: The use of HNS instead of normal saline irrigant during high
      power delivery targeting deep myocardial substrate is safe and effective. PVC/VT
      sources previously unaffected by standard ablation may be successfully ablated
      with improved efficiency of radiofrequency delivery using HNS.

PMID- 30236393
TI  - Trends and Outcomes of Catheter Ablation for Ventricular Tachycardia in a
      Community Cohort.
AB  - OBJECTIVES: This study examined the trend in growth of catheter ablation for
      ventricular tachycardia (VT) performed in the United States with analysis of
      rates and predictors of major adverse events. BACKGROUND: Sustained VT is a
      significant cause of sudden death, heart failure (HF), and recurrent shocks in
      implantable cardioverter-defibrillator (ICD) recipients. Catheter ablation for VT
      reduces arrhythmia recurrence. Limited data are available regarding the use,
      safety, and long-term outcomes after VT ablation. METHODS: Using the U.S.
      Medicare database linked to the Social Security Death Index, we examined the
      annual use of VT ablation in 21,073 patients over 12 years, with 30-day risk of
      mortality, nonfatal major adverse events (MAEs), 1-year risk of mortality, re
      hospitalization, repeat ablation, and factors associated with adverse outcomes.
      RESULTS: Among 21,073 patients (age 70 +/- 9 years; 77% men; 90% white), there
      were 1,581 (7.5%) non-fatal MAEs within 30 days. There were 963 (4.6%) vascular
      complications, 485 (2.3%) pericardial complications, and 201 (1%) strokes and/or
      transient ischemic attacks. Mechanical circulatory support use was infrequent
      (2.3%). The 30-day and 1-year mortality rates were 4.2% and 15.0%, respectively.
      The 1-year incidence of repeat ablation was 10.2 per 100 person-years and re
      hospitalization for HF or VT was 15.4 per 100 person-years and 18 per 100 person
      years, respectively. Patients with an ICD had increased 30-day (4.9% vs. 0.86%)
      and 1-year mortality (17.5% vs. 2.54% [22.9 per 100 person-years vs. 3.1 per 100
      person-years]; hazard ratio [HR]: 2.93; 95% confidence interval [CI]: 2.21 to
      3.88). Rates of hospitalization for HF (18 per 100 person-years vs. 1.8 per 100
      person-years; HR: 4.00; 95% CI: 2.78 to 5.78) or VT recurrence (22.7 per 100
      person-years vs. 2.1 per 100 person-years; HR: 5.70; 95% CI: 4.09 to 7.96) were
      also higher at 1 year. Between 2000 and 2012, annual VT ablation volumes
      increased >4-fold. CONCLUSIONS: Catheter ablation for VT is frequently performed.
      Short-term MAEs and 1-year mortality is significant and is highest in patients
      with an ICD. These findings may provide greater insight of outcomes in an
      unselected real-world population undergoing VT ablation.

PMID- 30236390
TI  - Predictors and Clinical Impact of Late Ventricular Arrhythmias in Patients With
      Continuous-Flow Left Ventricular Assist Devices.
AB  - OBJECTIVES: This study aimed to evaluate the incidence, clinical impact, and
      predictors of late ventricular arrhythmias (VAs) in left ventricular assist
      device (LVAD) recipients aiming to clarify implantable cardioverter-defibrillator
      (ICD) indications. BACKGROUND: The arrhythmic risk and need for ICD in patients
      implanted with an LVAD are not very well known. METHODS: This observational study
      was conducted in 19 centers between 2006 and 2016. Late VAs were defined as
      sustained ventricular tachycardia or fibrillation occurring >30 days post-LVAD
      implantation, without acute reversible cause and requiring appropriate ICD
      therapy, external electrical shock, or medical therapy. RESULTS: Among 659 LVAD
      recipients, 494 (median 58.9 years of age; mean left ventricular ejection
      fraction 20.7 +/- 7.4%; 73.1% HeartMate II, 18.6% HeartWare, 8.3% Jarvik 2000)
      were discharged alive from hospital and included in the final analysis. Late VAs
      occurred in 133 (26.9%) patients. Multivariable analysis identified 6 independent
      predictors of late VAs: VAs before LVAD implantation, atrial fibrillation before
      LVAD implantation, idiopathic etiology of the cardiomyopathy, heart failure
      duration >12 months, early VAs (<30 days post-LVAD), and no angiotensin
      converting enzyme inhibitors during follow-up. The "VT-LVAD score" was created,
      identifying 4 risk groups: low (score 0 to 1), intermediate (score 2 to 4), high
      (score 5 to 6), and very high (score 7 to 10). The rates of VAs at 1 year were
      0.0%, 8.0%, 31.0% and 55.0%, respectively. CONCLUSIONS: Late VAs are common after
      LVAD implantation. The VT-LVAD score may help to identify patients at risk of
      late VAs and guide ICD indications in previously nonimplanted patients.
      (Determination of Risk Factors of Ventricular Arrhythmias [VAs] after
      implantation of continuous flow left ventricular assist device with continuous
      flow left ventricular assist device [CF-LVAD] [ASSIST-ICD]; NCT02873169).

PMID- 30236395
TI  - Imaging to Evaluate the Substrate Underlying Sudden Cardiac Death.

PMID- 30236394
TI  - Myocardial Scar But Not Ischemia Is Associated With Defibrillator Shocks and
      Sudden Cardiac Death in Stable Patients With Reduced Left Ventricular Ejection
      Fraction.
AB  - OBJECTIVES: This study sought to investigate the association of myocardial scar
      and ischemia with major arrhythmic events (MAEs) in patients with left
      ventricular ejection fraction (LVEF) <=35%. BACKGROUND: Although myocardial scar
      is a known substrate for ventricular arrhythmias, the association of myocardial
      ischemia with ventricular arrhythmias in stable patients with left ventricular
      dysfunction is less clear. METHODS: A total of 439 consecutive patients (median
      age, 70 years; 78% male; 55% with implantable cardioverter defibrillator [ICD])
      referred for stress/rest positron emission tomography (PET) and resting LVEF
      <=35% were included. Primary outcome was time-to-first MAE defined as sudden
      cardiac death, resuscitated sudden cardiac death, or appropriate ICD shocks for
      ventricular tachyarrhythmias ascertained by blinded adjudication of hospital
      records, Social Security Administration's Death Masterfile, National Death Index,
      and ICD vendor databases. RESULTS: Ninety-one MAEs including 20 sudden cardiac
      deaths occurred in 75 (17%) patients during a median follow-up of 3.2 years.
      Transmural myocardial scar was strongly associated with MAEs beyond age, sex,
      cardiovascular risk factors, beta-blocker therapy, and resting LVEF (adjusted
      hazard ratio per 10% increase in scar, 1.48 [95% confidence interval: 1.22 to
      1.80]; p < 0.001). However, non transmural scar/hibernation or markers of
      myocardial ischemia on PET including global or peri-infarct ischemia, coronary
      flow reserve, and resting or hyperemic myocardial blood flows were not associated
      with MAEs in univariable or multivariable analysis. These findings remained
      robust in subgroup analyses of patients with ICD (n = 223), with ischemic
      cardiomyopathy (n = 287), and in patients without revascularization after the PET
      scan (n = 365). CONCLUSIONS: Myocardial scar but not ischemia was associated with
      appropriate ICD shocks and sudden cardiac death in patients with LVEF <=35%.
      These findings have implications for risk-stratification of patients with left
      ventricular dysfunction who may benefit from ICD therapy.

PMID- 30236396
TI  - Impact of Coronary Artery Chronic Total Occlusion on Arrhythmic and Mortality
      Outcomes: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: This study aimed to examine the relationship between chronic coronary
      artery total occlusion (CTO) status and the occurrence of ventricular tachycardia
      (VT)/ventricular fibrillation (VF) or appropriate implantable cardioverter
      defibrillator (ICD) therapy. BACKGROUND: CTO is a significant problem in patients
      with ischemic heart disease. However, the extent to which it predisposes affected
      individuals to VT/VF and whether these arrhythmic events could be prevented by
      revascularization are unclear. Therefore, a systematic review and meta-analysis
      were conducted to examine the relationship between CTO status and the occurrence
      of VT/VF or appropriate ICD therapy. METHODS: PubMed and Embase databases were
      searched until November 16, 2017, identifying 137 studies. RESULTS: Seventeen
      studies involving 54,594 subjects (mean age, 61 +/- 21 years of age, 81% male)
      with a mean follow-up of 43 +/- 31 months were included. The presence of CTO was
      associated with higher risk of VT/VF or appropriate ICD therapy (adjusted hazard
      ratio [aHR]: 1.99; 95% confidence interval (CI): 1.53 to 2.59; p < 0.0001, I2 =
      3%) but not in cardiac mortality (aHR: 2.59; 95% CI: 0.64 to 10.59; p = 0.18, I2
      = 86%) or in all-cause mortality (aHR: 1.70; 95% CI: 0.84 to 3.46; p = 0.14; I2 =
      64%). Compared to patients with non-infarct-related CTOs, those with infarct
      related CTOs have a higher risk of VT/VF or appropriate ICD therapy (aHR: 2.47;
      95% CI: 1.76 to 3.46; p < 0.0001; I2 = 14%), cardiac mortality (aHR: 2.73; 95%
      CI: 1.02 to 7.30; p < 0.05; I2 = 79%) and higher all-cause mortality (aHR: 1.69;
      95% CI: 1.19 to 2.40; p < 0.01; I2 = 40%). Nonrevascularization of CTOs tended to
      be associated with an increased risk of all-cause mortality compared to
      successful revascularization (unadjusted HR: 1.52; 95% CI: 0.96 to 2.43; p =
      0.08; I2 = 76). CONCLUSIONS: CTOs, especially infarct-related, are associated
      with high risk of VT/VF or appropriate ICD therapy and mortality. ICD
      implantation could be beneficial. However, it is not clear that revascularization
      has an impact on the outcome of patients with CTOs.

PMID- 30236397
TI  - Chronic Total Coronary Occlusion and Ventricular Tachycardia: Not Just an
      Electrophysiology Business?

PMID- 30236399
TI  - Cardiac Resynchronization Therapy Does Not Prevent Atrial Fibrillation But Atrial
      Fibrillation Prevents Cardiac Resynchronization Therapy and Adversely Impacts
      Outcomes.

PMID- 30236398
TI  - Development of Heart Failure From Transient Atrial Fibrillation Attacks in
      Responders to Cardiac Resynchronization Therapy.
AB  - OBJECTIVES: This study aimed to clarify the clinical impact of transient atrial
      fibrillation (AF) attacks themselves and the efficacy of cardiac
      resynchronization therapy (CRT) in patients with intermittent AF. BACKGROUND: The
      benefit of CRT in patients with intermittent AF, especially the effect of the AF
      attacks themselves, remains unclear. METHODS: Among our cohort of 269 consecutive
      CRT patients, we compared the percent of biventricular pacing (BIVP%) and other
      clinical characteristics between patients with intermittent AF and those with
      sinus rhythm (SR). RESULTS: During a median follow-up of 942 days (interquartile
      range: 379 to 1,464 days) a total of 22 patients, including 59% of CRT
      responders, developed heart failure (HF) due to a transient AF attack itself, and
      that accounted for 21% of all HF events. The BIVP% during the AF attacks was
      significantly lower than that during SR (p < 0.05). When compared to the SR
      groups, patients with intermittent AF had a significantly higher risk of
      developing HF or death (hazard ratio: 2.2; 95% confidence interval: 1.3 to 3.8).
      However, the patients who received a BIVP% of >=90% during AF attacks were
      comparable to those with SR (hazard ratio: 1.2; 95% confidence interval: 0.4 to
      3.0). CONCLUSIONS: A substantial number of patients developed HF due to transient
      AF attacks themselves even in the CRT responders, and the reason was mainly due
      to the loss of the BIVP%.

PMID- 30236400
TI  - Clinical Significance of Early Repolarization in Long QT Syndrome.
AB  - OBJECTIVES: This study sought to determine the prevalence of early repolarization
      pattern (ERP) within a large cohort of patients with long QT syndrome (LQTS) and
      examine the correlation and clinical significance of ERP with symptomatic status
      and subsequent risk of breakthrough cardiac events (BCEs). BACKGROUND: The
      electrocardiographic ERP is associated with an increased risk of arrhythmic
      events and sudden cardiac death. METHODS: ERP was defined as an end-QRS notch or
      slur on the downslope of a prominent R-wave with a J point >=0.1 mV in 2 or more
      contiguous leads of the 12-lead electrocardiogram, excluding V1 to V3. A patient
      was considered previously symptomatic if they had a suspected LQTS-triggered
      cardiac event prior to diagnosis. BCEs were defined as LQTS-attributable
      syncope/seizures, aborted cardiac arrest, appropriate ventricular fibrillation
      terminating implantable cardioverter-defibrillator shocks, and sudden cardiac
      death following diagnosis and institution of a LQTS-directed treatment program.
      RESULTS: In this study, 528 patients (57% female) with genotype-confirmed LQTS
      (283 with LQT1, 193 with LQT2, and 52 with LQT3) were reviewed from which 2,618
      electrocardiograms were analyzed over a median follow-up of 6.7 (interquartile
      range, 3.6 to 10 years) years. Eighty-two (15.5%; female 51%) patients were
      identified as having ERP; 40 (50%) of these ERP-positive patients showed
      persistent ERP. One hundred twenty-four patients (23.5%) were classified as
      previously symptomatic LQTS and 39 (7.2%) experienced a subsequent BCE. ERP was
      not associated with either symptomatic status (p = 0.62) or BCE (p = 0.61).
      CONCLUSIONS: Although ERP is common in LQTS, this extensive study suggests that
      the presence of concomitant ERP does not correlate with either those with a
      history of LQTS-triggered events prior to diagnosis or those with subsequent BCEs
      from their treated LQTS substrate.

PMID- 30236401
TI  - Early Repolarization in Long QT Syndrome: Modifier of Arrhythmic Risk or Benign
      Incidental Finding?

PMID- 30236402
TI  - Multifocal Ventricular Arrhythmias Originating From the His-Purkinje System:
      Incidence, Characteristics, and Outcome of Catheter Ablation.
AB  - OBJECTIVES: This study sought to reveal the characteristics and radiofrequency
      catheter ablation (RFCA) outcomes of multifocal His-Purkinje system (HPS)
      ventricular arrhythmias (VAs). BACKGROUND: The details of those VAs, especially
      the safety and efficacy of their RFCA treatment, remain unclear. METHODS: Thirty
      consecutive patients who underwent RFCA of focal HPS VAs between 2010 and 2016
      (unifocal = 24, multifocal = 6) were studied by measuring the
      electrophysiological variables within the HPS. RESULTS: Multifocal premature
      ventricular contractions (n = 1) and ventricular fibrillation (VF) (n = 5) were
      identified in the left posterior (n = 6), anterior (n = 4), and septal fascicles
      (n = 1), as well as the basal left bundle branch (LBB) (n = 2) and right bundle
      branch (RBB) (n = 2). In 2 patients with unifocal VAs and 4 patients with
      multifocal VAs, preferential conduction from an origin within the proximal
      fascicle (n = 4) or LBB (n = 2) to <=3 breakout sites in the distal fascicles
      occurred with split or fractionated Purkinje potentials and/or conduction block
      at the site of origin. Among the multifocal VAs, 11 fascicle VAs, 1 RBB VA, and 1
      LBB VA were successfully ablated with fascicular and/or bundle branch block, and
      complete atrioventricular block (CAVB), respectively. In the remaining LBB VAs
      and RBB VAs, RFCA was abandoned to avoid CAVB. Recurrence of ablated VAs or the
      incidence of VF did not differ between the unifocal and multifocal HPS VAs.
      Freedom from any HPS VA after RFCA was significantly higher in the patients with
      unifocal VAs than in the patients with multifocal VAs (92% vs. 33%; p = 0.001).
      CONCLUSIONS: Multifocal HPS VAs could occur and often present with preferential
      conduction from proximal origins to distal breakout sites within the HPS with
      abnormal Purkinje potentials and/or conduction properties. RFCA was effective but
      was limited by the risk of HPS impairment.

PMID- 30236403
TI  - Multicenter Experience of Concomitant Use of Left Ventricular Assist Devices and
      Subcutaneous Implantable Cardioverter-Defibrillators.

PMID- 30236404
TI  - Catheter Ablation of Mid-Myocardial Ventricular Tachycardia by Simultaneous
      Unipolar Radiofrequency Ablation With Half-Normal Saline Irrigation.

PMID- 30236405
TI  - First Simultaneous Endocardial and Epicardial Mapping of a Ventricular
      Tachycardia in an ARVD/C Patient.

PMID- 30236406
TI  - Epicardial and Subsequent Endocardial Ablation in a Patient With Brugada
      Syndrome.

PMID- 30236408
TI  - Intranasal Osteosarcoma in a Dog-A Case Report.
AB  - Osteosarcoma is the most commonly reported bone tumor in dogs, typically
      affecting the axial and appendicular skeleton. Involvement of the paranasal
      sinuses and the nasal cavity is extremely rare. This report describes a 6-year
      old, female, cross-breed dog presented with signs of 90 days duration and
      diagnosed with a mass located in the right nasal cavity. Radiography, rhinoscopy,
      and computed tomography findings suggested the presence of an intranasal tumor.
      Osteosarcoma in the nasal cavity was diagnosed based on histopathological
      examination and clinical and imaging findings. Survival time was 12 months from
      diagnosis.

PMID- 30236409
TI  - Veterinary Neurologic Rehabilitation: The Rationale for a Comprehensive Approach.
AB  - The increase in client willingness to pursue surgical procedures, the heightened
      perceived value of veterinary patients, and the desire to provide comprehensive
      medical care have driven the recent demand of using an integrative treatment
      approach in veterinary rehabilitation. Physical therapy following neurologic
      injury has been the standard of care in human medicine for decades, whereas
      similar rehabilitation techniques have only recently been adapted and utilized in
      veterinary medicine. Spinal cord injury is the most common neurologic disease
      currently addressed by veterinary rehabilitation specialists and will be the
      primary focus of this review; however, research in other neurologic conditions
      will also be discussed. Of particular interest, to clients and veterinarians are
      techniques and modalities used to promote functional recovery after neurologic
      injury, which can mean the difference between life and death for many veterinary
      patients. The trend in human neurologic rehabilitation, often regardless of
      etiology, is a multimodal approach to therapy. Evidence supports faster and
      improved recoveries in people after neurologic injury using a combination of
      rehabilitation techniques. Although the primary neurological disorders researched
      tend to be spinal cord injury, peripheral neuropathies, allodynia, multiple
      sclerosis, and strokes-many correlations can be made to common veterinary
      neurological disorders. Such comprehensive protocols entail gait training
      activities in combination with neuromuscular electrical stimulation and directed
      exercises. Additionally, pain-relieving and functional benefits are bolstered
      when acupuncture is used in addition to rehabilitation. Studies, both laboratory
      and clinical, support the use of acupuncture in the management of neurologic
      conditions in small animals, specifically in cases of intervertebral disc
      disease, other myelopathies, and neuropathic pain conditions. Acupuncture's
      ability to promote analgesia, stimulate trophic factors, and decrease
      inflammation, including neuroinflammation, make it an alluring adjunct therapy
      after neurologic injury. Although there is limited research in veterinary
      medicine on physical techniques that expedite recovery after neurologic injury,
      there are sparse publications on clinical veterinary research suggesting the
      benefits of acupuncture, rehabilitation, and LASER in dogs with intervertebral
      disk disease. Accordingly, due to the relative lack of evidence-based studies in
      veterinary neurologic rehabilitation, much of the data available is human or
      laboratory-animal based, however, evidence supports the utilization of an early,
      comprehensive treatment protocol for optimal neurologic recovery. The rationale
      for why an integrative approach is critical will be detailed in this review; in
      addition, literature on specific physical rehabilitation techniques that have
      evidence of improved recoveries after neurologic injury, will be addressed.

PMID- 30236410
TI  - Readability Evaluations of Veterinary Client Handouts and Implications for
      Patient Care.
AB  - Health literacy and readability are important considerations for veterinary
      medicine, as veterinarians commonly distribute brochures, leaflets and info
      graphics to explain health related issues to pet owners. Educational materials
      that are poorly comprehended by the intended audience could result in negative,
      unintended consequences. Thus, the National Institutes of Health (NIH) and the
      American Medical Association (AMA) have recommended readability levels for text
      on health information be targeted between the fourth and sixth grade levels to
      accommodate a highly diverse public. In the context of veterinary medicine, an
      increased awareness among veterinary professionals and educators regarding
      readability scores and the tools available to generate "easy-to-read" text would
      likely benefit client adherence with veterinary recommendations, client
      satisfaction with their veterinarian, and ultimately, pet health. Therefore, the
      goal of this study was to evaluate the readability levels of a sample of popular
      client handout materials prepared expressly for veterinarians to download and
      distribute to their pet-owning clients. Results indicate that 9 of 10 client
      brochures were written above the recommended sixth grade reading level.
      Recommendations for improving readability are provided.

PMID- 30236411
TI  - Towards recognition of seagrasses, and their sustainable management.

PMID- 30236412
TI  - Long-term outcomes of sport-related brain injuries: A psychophysiological
      perspective.

PMID- 30236413
TI  - Using molecular simulations to probe pore structures and polymer partitioning in
      size exclusion chromatography.
AB  - Molecular simulations have been extensively utilized to understand and predict
      the polymer partitioning in size-exclusion chromatography (SEC). However,
      idealized pore models (e.g., cylindrical, spherical, and slit pores) were often
      used to represent the porous media in an SEC column, which leads to significant
      deviations in describing the geometry and the size of the pores. In this work,
      several complex pore models were derived from body-centered cubic, random, and
      gel packing of monodisperse spherical sol particles using simulation methodology.
      The mechanical stabilities of these structures were determined based on particle
      coordination numbers. Pore size distributions of these porous structures were
      compared to a commercially available, wide-pore superficially porous particle.
      Then, Gibbs ensemble Monte Carlo simulations were performed to compute the pore
      to-bulk partitioning coefficient KSEC of a polymer chain with complex pore
      models. The effects of particle size, packing structure, and porosity on KSEC
      were explored. In addition, structural analysis provides insight into the
      conformation of polymers in the pores and its effect on the partitioning
      behavior. This study promotes the understanding of pore structures in SEC columns
      and enables more accurate predictions of KSEC with less ambiguity in pore
      geometry.

PMID- 30236414
TI  - [Acute disseminated encephalomyelitis due to Mycoplasma pneumoniae in a
      previously healthy boy].
AB  - We present here the case of a previously healthy 5 year-old boy hospitalized in
      an intensive care unit due to tonic-clonic seizures focused on the face and right
      side of the body, and axillary temperature of 37.4 degrees C. Common bacterial
      and viral etiology was ruled out through studies of cerebrospinal fluid (CSF)
      samples. Mycoplasma pneumoniae was suspected by a positive immunofluorescence
      serum test for IgM class antibodies. Finally, with a brain biopsy, M. pneumoniae
      was confirmed by polymerase chain reaction (PCR) and acute disseminated
      encephalomyelitis by pathological anatomy. The patient was treated with
      clarithromycin and had an uneventful evolution. At least to our knowledge, this
      is the first case in which M. pneumoniae DNA was detected by PCR in a brain
      biopsy.

PMID- 30236415
TI  - Application of machine-learning to predict early spontaneous preterm birth among
      nulliparous non-Hispanic black and white women.
AB  - PURPOSE: Spontaneous preterm birth is a leading cause of perinatal mortality in
      the United States, occurring disproportionately among non-Hispanic black women
      compared to other race-ethnicities. Clinicians lack tools to identify first-time
      mothers at risk for spontaneous preterm birth. This study assessed prediction of
      early (<32 weeks) spontaneous preterm birth among non-Hispanic black and white
      women by applying state-of-the-art machine-learning to multilevel data from a
      large birth cohort. METHODS: Data from birth certificate and hospital discharge
      records for 336,214 singleton births to nulliparous women in California from 2007
      to 2011 were used in cross-validated regressions, with multiple imputation for
      missing covariate data. Residential census tract information was overlaid for
      281,733 births. Prediction was assessed with areas under the receiver operator
      characteristic curves (AUCs). RESULTS: Cross-validated AUCs were low (0.62 [min =
      0.60, max = 0.63] for non-Hispanic blacks and 0.63 [min = 0.61, max = 0.65] for
      non-Hispanic whites). Combining racial-ethnic groups improved prediction (cross
      validated AUC = 0.67 [min = 0.65, max = 0.68]), approaching what others have
      achieved using biomarkers. Census tract-level information did not improve
      prediction. CONCLUSIONS: The resolution of administrative data was inadequate to
      precisely predict individual risk for early spontaneous preterm birth despite the
      use of advanced statistical methods.

PMID- 30236416
TI  - Fast Protocol for Treating Acute Ischemic Stroke by Emergency Physicians.
AB  - STUDY OBJECTIVE: Thrombolysis with tissue plasminogen activator should occur
      promptly after ischemic stroke onset. Various strategies have attempted to
      improve door-to-needle time. Our objective is to evaluate a strategy that uses an
      emergency physician-based protocol when no stroke neurologist is available.
      METHODS: This was a retrospective before-after intervention analysis in an urban
      hospital. Reorganization of the acute ischemic stroke treatment process was
      carried out in 2013. We evaluated time delay, symptomatic intracerebral
      hemorrhage, and clinical recovery of patients before and after the
      reorganization. We used multivariable linear regression to estimate the change in
      door-to-needle time before and after the reorganization. RESULTS: A total of 107
      patients with comparable data were treated with tissue plasminogen activator in
      2009 to 2012 (group 1) and 46 patients were treated during 12 months in 2013 to
      2014 (group 2). Median door-to-needle time was 54 minutes before the
      reorganization and 20 minutes after it (statistical estimate of difference 32
      minutes; 95% confidence interval 26 to 38 minutes). After adjusting for several
      potential cofounders in multivariable regression analysis, the only factor
      contributing to a significant reduction in delay was group (after reorganization
      versus before). Median onset-to-treatment times were 135 and 119 minutes,
      respectively (statistical estimate of difference 23 minutes; 95% confidence
      interval 6 to 39 minutes). The rates of symptomatic intracerebral hemorrhage were
      4.7% (5/107) and 2.2% (1/46), respectively (difference 2.5%; 95% confidence
      interval -8.7% to 9.2%). Approximately 70% of treated patients were functionally
      independent (modified Rankin Scale score 0 to 2) when treated after the
      reorganization. CONCLUSION: Implementation of a stroke protocol with emergency
      physician-directed acute care decreased both door-to-needle time and onset-to
      treatment time without increasing the rate of symptomatic intracerebral
      hemorrhage.

PMID- 30236417
TI  - Should Adults With Mild Head Injury Who Are Receiving Direct Oral Anticoagulants
      Undergo Computed Tomography Scanning? A Systematic Review.
AB  - STUDY OBJECTIVE: Patients receiving direct oral anticoagulant medications
      commonly undergo computed tomography head scanning after mild traumatic brain
      injury, regardless of symptoms or signs. International guidelines have noted a
      lack of evidence to support management decisions for such patients. This
      systematic review aims to identify, appraise, and synthesize the current evidence
      for the risk of adverse outcome in patients receiving direct oral anticoagulants
      after mild head injury. METHODS: A protocol was registered with PROSPERO and
      review methodology followed Cochrane Collaboration recommendations. Studies of
      adult patients with mild head injury (Glasgow Coma Scale score 13 to 15) and who
      were receiving direct oral anticoagulants that reported the risk of adverse
      outcome after the head injury were eligible for inclusion. A comprehensive range
      of bibliographic databases and gray literature was examined with a sensitive
      search strategy. Selection of eligible studies, data extraction, and risk of bias
      were evaluated independently by separate reviewers. A random-effects meta
      analysis was used to provide a pooled estimate of the risk of adverse outcome.
      The overall quality of evidence was assessed with the Grading of Recommendations
      Assessment, Development and Evaluation Working Group approach. RESULTS: A total
      of 4,886 articles were screened for inclusion, of which 7 cohort studies
      including 346 patients met inclusion criteria. All studies were at high or
      unclear risk of bias as a result of selection and information bias. Estimates of
      adverse outcome (any death, intracranial hematoma, or neurosurgery) ranged from
      0.0% to 8.3%. A random-effects meta-analysis showed a weighted composite outcome
      risk of 3.7% (95% confidence interval 1.7% to 5.8%; I2=3.3%). The overall quality
      of the body of evidence was low as a result of imprecision, indirectness, and
      risk of bias. CONCLUSION: There are limited data available to characterize the
      risk of adverse outcome in patients receiving direct oral anticoagulants after
      mild traumatic brain injury. A sufficiently powered prospective cohort study is
      required to validly define this risk, identify clinical features predictive of
      adverse outcome, and inform future head injury guidelines.

PMID- 30236418
TI  - Expanding Health Information Exchange Improves Identification of Frequent
      Emergency Department Users.
AB  - STUDY OBJECTIVE: Frequent emergency department (ED) users are of interest to
      policymakers and hospitals. The objective of this study is to examine the effect
      of health information exchange size on the identification of frequent ED users.
      METHODS: We retrospectively analyzed data from Healthix, a health information
      exchange in New York that previously included 10 hospitals and then grew to 31
      hospitals. We divided patients into 3 cohorts: high-frequency ED users with 4 or
      more visits in any 30-day period, medium-frequency ED users with 4 or more visits
      in any year, and infrequent ED users with fewer than 4 visits in any year. For
      both the smaller (10-hospital) and larger (31-hospital) health information
      exchanges, we compared the identification rate of frequent ED users that was
      based on hospital-specific data with the corresponding rates that were based on
      health information exchange data. RESULTS: The smaller health information
      exchange (n=1,696,279 unique ED patients) identified 11.4% more high-frequency
      users (33,467 versus 30,057) and 9.5% more medium-frequency users (109,497 versus
      100,014) than the hospital-specific data. The larger health information exchange
      (n=3,684,999) identified 19.6% more high-frequency patients (52,727 versus
      44,079) and 18.2% more medium-frequency patients (222,574 versus 192,541) than
      the hospital-specific data. Expanding from the smaller health information
      exchange to the larger one, we found an absolute increase of 8.2% and 8.7%
      identified high- and medium-frequency users, respectively. CONCLUSION: Increasing
      health information exchange size more accurately reflects how patients access EDs
      and ultimately improves not only the total number of identified frequent ED users
      but also their identification rate.

PMID- 30236419
TI  - Making a lecture memorable.
AB  - INTRODUCTION: The key elements of a lecture that promote retention and
      understanding of material have been extensively described, although both the
      understanding and use of these principles by lecturers is a significant time and
      resource investment. Lecturers in healthcare are a broad group of people, many of
      which have other commitments and may lack prior formal teaching experience.
      PERSPECTIVE: This commentary describes an essential version of the cognitive
      theories of learning and presents an assimilated and reduced version of these
      theories in the form of the acronym 'MAKE' (make it memorable, add value, keep
      audience interest, entertain) to enable the more rapid development of memorable
      lectures and reduce the time required to improve them. IMPLICATIONS: There is a
      fine line between a lecture that engages and inspires the audience and one that
      is unimaginative and poorly planned. All lecturers should be encouraged to use
      simple evidence-based methods to improve engagement, retention and student
      satisfaction. The easy to understand and share nature of the "MAKE" acronym could
      help achieve these aims.

PMID- 30236420
TI  - Development of critical thinking in health professions education: A meta-analysis
      of longitudinal studies.
AB  - INTRODUCTION: While reports of critical thinking exist in the health professions
      literature, development of critical thinking across a broad range of health
      professions students has not been systematically reviewed. METHODS: In this meta
      analysis, multiple databases and journals were searched through February 2016 to
      identify longitudinal studies using standardized tests of critical thinking
      [California Critical Thinking Skills Test (CCTST), Health Science Reasoning Test
      (HSRT), and Defining Issues Test (DIT)] in any language. Two reviewers extracted
      information and collected information regarding primary author, publishing
      journal, health profession, critical thinking test, and time1/time2 means and
      standard deviations. Standardized mean differences (SMD) with 95% confidence
      intervals (CI) were reported using a random-effects model. RESULTS: Four hundred
      sixty-two studies were screened, and 79 studies (representing 6884 students) were
      included. Studies contained 37 CCTST, 22 DIT, and 20 HSRT. Health professions
      comprised nursing, pharmacy, physical therapy, occupational therapy, dentistry,
      medicine, veterinary medicine, dental hygiene, clinical laboratory sciences, and
      allied health. Cohen's kappa was strong (0.82) for inter-reviewer agreement. Both
      the CCTST (SMD = 0.37, 95% CI = 0.23-0.52) and DIT (SMD = 0.28, 95%CI = 0.18
      0.39) demonstrated significant increases in total scores, but the HSRT (SMD =
      0.03, 95%CI = -0.05-0.12) did not show improvement. DISCUSSION/CONCLUSIONS: In
      this meta-analysis, students from the majority of health professions consistently
      showed improvement in development of critical thinking. In this diverse
      population, only the CCTST and DIT appeared responsive to change.

PMID- 30236421
TI  - Comparison of perceived personality traits between the pharmacy residents
      admitted through the match or scramble process.
AB  - INTRODUCTION: The purpose of this study is to determine whether certain
      personality traits are as prominent in pharmacy practice residents who obtain
      positions through the post-Match process, previously referred to as the Scramble,
      as compared to residents who match directly with programs. METHODS: Pharmacy
      residency program directors (RPDs) across the United States were asked to
      complete an electronic survey that gauged RPD perceptions of 13 personality
      traits commonly seen in pharmacy residents. RPDs were requested to separately
      evaluate residents who Scrambled and Matched to their respective programs.
      Exploratory factor analysis (EFA) was used to determine factor structure for the
      personality traits and to assess whether factors associate differentially between
      Matched and Scrambled residents. RESULTS: A total of 1876 RPDs of post-graduate
      year one (PGY1), post-graduate year two (PGY2), and combined PGY1 and PGY2
      pharmacy residency programs were contacted for study participation with a
      response rate of 21 percent. Demographic variables related to program type and
      number of residents per class were similar between Scrambled and Matched groups.
      The EFA identified two factors across 13 traits: we termed them as traditional
      traits and grit-like traits, and they significantly differed between the Scramble
      and Match groups. RPD perception of traditional traits (nine traits) were
      significantly higher in the Match group (p < 0.05), whereas perceived grit-like
      traits (four traits) were significantly higher in the Scramble group (p <
      0.0001). CONCLUSION: Residency candidates who Match versus candidates who
      Scramble are perceived to have unique and significantly different personality
      traits.

PMID- 30236422
TI  - Preadmission predictors of academic performance in a pharmacy program: A
      longitudinal, multi-cohort study.
AB  - INTRODUCTION: This study examined the extent to which a preadmission health
      science program and demographic variables predicted academic performance
      throughout an undergraduate pharmacy degree (BPharm) program. METHODS: A
      longitudinal, multi-cohort study was undertaken of 557 students admitted to the
      University of Otago School of Pharmacy BPharm program between 2008 and 2012, from
      a preceding health science year (HSFY). Preadmission baseline data including
      health science grade point average (GPA), sex, age, ethnicity, residency status,
      and high school qualifications were matched against outputs of GPA performances
      in all three years of the BPharm program using regression analyses. RESULTS: Five
      hundred thirty-eight students (96.6%) completed their BPharm degree. The
      regression models were significantly predictive of performance in the BPharm
      program with 57%, 43% and 38% of variances explained for GPA performance across
      years two, three and four, respectively (p < 0.001). Demographic variables
      including being male, being from certain minority ethnic groups or not having a
      specific domestic high school qualification were associated with lower GPA
      performances across the BPharm program compared to reference groups. DISCUSSION
      AND CONCLUSIONS: Determining admission from performance rankings as the single
      selection tool holds reasonable predictive value early in progression, however
      additional measures may be warranted to better predict performances extending
      beyond the first year of the BPharm program.

PMID- 30236423
TI  - The satisfaction and perception of Provisionally Registered Pharmacists (PRP)
      towards their internship training in the Ministry of Health, Malaysia facilities:
      A national survey.
AB  - BACKGROUND: The pharmacy internship program is designed to provide comprehensive
      training for interns to perform various roles in pharmacy practice. In Malaysia,
      the current internship program has been in place since 2004 in public health
      facilities, but has never been extensively evaluated. AIM: To assess the level of
      job satisfaction and perception of Provisionally Registered Pharmacists (PRP)
      towards the internship training provided. METHODS: A cross-sectional nationwide
      survey was conducted amongst all PRPs undergoing training between December 2015
      and February 2016 to assess their level of job satisfaction and perception
      towards the training requirements stipulated by the Pharmacy Board of Malaysia.
      RESULTS: A total of 733 PRPs participated in the survey and the response rate was
      95.8%. On the basis of the response received, 92.5% (n = 678) felt that the one
      year training period was 'just nice', 30.5% (n = 223) felt that the logbooks were
      'too complicated', and 33.2% (n = 241) said the targets set by the Pharmacy Board
      of Malaysia were 'too high'. On a scale of 1 to 5, respondents rated 3.32 (SD
      0.54) for mean score of job satisfaction. Significant factors influencing mean
      score of job satisfaction were: perceived fairness at the work place; perceived
      self-competence after one year of training; preceptors' competence; and pharmacy
      as a chosen career pathway. CONCLUSION: Intern pharmacists were fairly satisfied
      with the internship training in government facilities in the Ministry of Health,
      Malaysia. A review of the internship logbooks and the practicality of targets set
      by the Pharmacy Board warrant further improvement.

PMID- 30236424
TI  - A comparison of baseline professional attitudes and behaviors among student
      pharmacists to inform a co-curricular professional engagement program.
AB  - BACKGROUND: Professionalism in pharmacy students is an area of great focus with
      the release of Accreditation Council for Pharmacy Education (ACPE) Standards
      2016. This study assessed and compared student pharmacists' professionalism at
      one college of pharmacy to inform the implementation of a co-curricular
      professional engagement program. METHODS: Two validated instruments (Behavioral
      Professionalism Assessment Instrument [BPAI] and Pharmacy Professionalism
      Instrument [PPI]) were administered to assess baseline professionalism. Kruskall
      Wallis tests compared responses among the three pharmacy classes. Analysis was
      conducted using SPSS. This research was approved by the Mercer University's
      Institutional Review Board. RESULTS: A total of 362 students completed the survey
      (75% response rate), of which 131 were first-year, 139 were second-year, and 92
      were third-year students. There were significant differences in agreement among
      these classes of students as to whether a program focused on professional
      engagement was important and helpful (p < 0.001). Seven BPAI statements and five
      PPI statements demonstrated significant differences in the level of agreement
      among the professional years. These behaviors include: completing assignments
      independently and without supervision (p = 0.004); commitment to helping others
      (p = 0.004); reporting a medication error (p = 0.005); using time efficiently (p
      = 0.02); and being respectful (p = 0.04). DISCUSSION: At baseline, 12 statements
      were significantly different in the level of agreement among the three pharmacy
      classes. Differences may be explained by perceived professionalism (in first-year
      students) versus actual professional behaviors (second- and third-year students),
      as well as breadth and depth of experience. A co-curricular professional
      engagement program could increase student awareness of professionalism and
      professional behaviors and be tailored to meet assessed student needs.

PMID- 30236425
TI  - Mentoring pharmacy staff to implement a medication support service: An evaluation
      of process and outcomes.
AB  - INTRODUCTION: To investigate the effectiveness of mentoring of pharmacy staff as
      they implemented a medication support service for mental health consumers. In
      particular, to show the relevance and applicability of Kram's four phases of
      mentoring to short-term mentoring relationships, the type of mentoring functions
      provided, and the value of utilising a pharmacist-consumer mentoring pair.
      METHOD: 163 pharmacy staff (mentees) each participated in a one-day workshop
      prior to implementing the service and being mentored over a period of six months.
      Data were collected from mentees via pre- and post-training questionnaires, and
      from mentors in the form of diaries, field notes, and a focus group. Quantitative
      and qualitative analyses were employed. RESULTS: Kram's 4-phase model is relevant
      and applicable to short-term mentoring relationships. Mentoring functions
      increased after initiation, peaked during cultivation, and decreased during
      separation and redefinition. According to the mentors, both mentees and mentors
      benefitted from utilising a pair of mentors, each of whom had particular
      knowledge, experience, and perspectives to share. CONCLUSIONS: This study extends
      mentoring research by showing that Kram's four phases could be intentionally
      integrated into the planning and implementation of mentoring relationships;
      moreover in short-term relationships. In addition, it has identified the
      particular mentoring functions that are sought and provided in different phases
      of relationships and that quantity of mentoring changes over the course of a
      relationship. Further, the study has found that mentees benefit from pairs of
      mentors (in this case a pharmacist and a consumer or carer) who provide different
      insights, knowledge and perspectives. Individuals and health-related
      organisations embarking on mentoring could use these findings as a guide to
      develop successful mentoring relationships, particularly when implementing a new
      service.

PMID- 30236426
TI  - Preceptor confidence and engagement in providing leadership activities to
      students in advanced pharmacy practice experiences.
AB  - INTRODUCTION: Preceptor perceptions about providing leadership activities during
      the fourth year of the doctor of pharmacy curriculum were examined. METHODS: An
      anonymous questionnaire was sent electronically to 610 preceptors of fourth year
      doctor of pharmacy students in August 2015 inquiring about confidence in
      leadership ability, extent of student engagement in leadership activities, and
      preceptor support needed. Differences based on leadership background, such as
      formal training, were examined using independent t-test. Continuous data are
      presented as mean (standard deviation). P-value < 0.05 was considered
      significant. RESULTS: Survey response rate was 28% (n = 171). Preceptor
      confidence in ability to provide leadership activities was 7.38 + /-1.66 [0-10
      Likert scale; 0 = cannot do at all, 10 = highly certain can do]. Preceptors were
      most confident teaching that leadership comes from those with and without titles
      (8.48 + /-1.64) and least confident engaging students in advocacy (5.41 + /
      3.02). Preceptors were most likely to engage students in collaboration [3(1-4)]
      and least likely to involve them in advocacy [1(1-4)] (measured from 1-4 with 1 =
      never and 4 = very often). Preceptors with formal leadership training
      demonstrated higher confidence and more engagement with involving students in
      leadership activities than those without training (p < 0.05). Examples of common
      leadership activities shared by preceptors included experiential clinical
      activities and projects, teaching opportunities, discussions with leaders, and
      participation in meetings. Leadership training and development was the most
      requested type of support by preceptors (n = 23, 13.5%). CONCLUSION: Preceptors
      were overall confident about their ability to provide leadership activities, were
      involving students in some leadership activities, and had the least confidence
      and engagement in involving students in advocacy. Preceptors may consider
      increasing engagement in teaching student leadership skills by utilizing examples
      in this study. Colleges of pharmacy and organizations may collaborate to increase
      preceptor access to formal leadership training programs and offer preceptor
      development programs designed to enhance preceptors' abilities to facilitate
      student leadership experience, reflection on experience, and feedback.

PMID- 30236427
TI  - Evaluation of the relationships among happiness, stress, anxiety, and depression
      in pharmacy students.
AB  - INTRODUCTION: To present the results of a survey on stress, anxiety, depression,
      subjective happiness, and academic satisfaction among pharmacy students. METHODS:
      A total of 410 pharmacy students, were included. Sociodemographic
      characteristics, stress, anxiety and depressive symptoms, and happiness were
      evaluated using the Perceived Stress Scale (PSS), Hospital Anxiety and Depression
      Scale (HADS), and Subjective Happiness Scale (SHS), in May 2015. RESULTS: First
      and second year student's (n = 200) presented higher levels of academic
      satisfaction (p = 0.003) and lower levels of stress (p < 0.001), anxiety (p =
      0.011) and depression (p = 0.010) than third and fourth year students (n = 210).
      Academic satisfaction, HADS, and the PSS explained 36.7% of the students'
      happiness. CONCLUSIONS: The student's psychological distress, academic
      satisfaction, and happiness varies through the school years. Monitoring a
      probable cumulative effect during pharmacy school may contribute to identify
      students at risk.

PMID- 30236428
TI  - Emotional intelligence scores among three cohorts of pharmacy students before and
      after completing the University of Oklahoma College of Pharmacy's Leadership
      Degree Option Program.
AB  - BACKGROUND AND PURPOSE: Report change in Emotional Intelligence Appraisal scores
      among three cohorts of student pharmacists before and after completing the
      Leadership Degree Option (LDO) Program within the University of Oklahoma College
      of Pharmacy. EDUCATIONAL ACTIVITY AND SETTING: The first three cohorts of student
      pharmacists who elected to enroll in the College's LDO completed the self
      administered Emotional Intelligence Appraisal, Me Edition, at the start of the
      LDO program and again three years later at the end of the program. Paired samples
      t-test compared differences between mean pre- and post-scores stratified by
      gender. FINDINGS: A total of 36 students from Cohorts 1, 2, and 3 completed and
      voluntarily reported their scores of the Emotional Intelligence Appraisal. There
      was a statistically significant increase in mean overall Emotional Intelligence
      Appraisal score between the start and end of the LDO (pre = 76.39, post = 81.03,
      p < 0.0001). Statistical significance remained when stratified by gender. There
      also were statistically significant differences on various sub-domain scores.
      DISCUSSIONS AND CONCLUSIONS: We observed a before and after increase in Emotional
      Intelligence Appraisal scores among three cohorts of pharmacy students who
      completed a three-year LDO Program in parallel with completing the Doctor of
      Pharmacy Degree Program. Emotional recognizance and management in oneself and
      others has potential to build leadership capacity that can be applied in the
      health-care delivery setting.

PMID- 30236430
TI  - Evaluation of a Newly Established Layered Learning Model in an Ambulatory Care
      Practice Setting.
AB  - BACKGROUND AND PURPOSE: Given the need to accommodate overlapping longitudinal
      Introductory Pharmacy Practice Experience (IPPE) students and Advanced Pharmacy
      Practice Experience (APPE) students at regular intervals while meeting clinical
      demands, the opportunity to establish a layered learning model (LLM) became
      evident at University of Missouri - Kansas City School of Pharmacy. The purpose
      of this project was to establish an LLM at an ambulatory care site, observe the
      teaching-learning interactions between IPPE and APPE students, and evaluate
      student perceptions of the experience. EDUCATIONAL ACTIVITY AND SETTING: The LLM
      was implemented over the course of three traditional semesters during Spring 2016
      through Spring 2017. Clinical services were offered 2.5 days per week.
      Overlapping student instructional time was established in conjunction with the
      provision of clinical pharmacy services and the structure of each rotation type.
      Third-year (P3) IPPE and fourth-year (P4) APPE students, who participated in the
      LLM at this site, completed a course evaluation pertaining to their experiences.
      The evaluation focused on APPE and practice readiness, as well as strengths and
      limitations of the LLM. FINDINGS: All 16 students completed the evaluation (100%
      response rate). All IPPE students indicated the LLM prepared them for APPEs in
      either an excellent (n=3, 37.5%) or above average (n=5, 62.5%) manner. Of the
      APPE students, most indicated the LLM prepared IPPE students for APPEs in an
      excellent (n=3, 37.5%) or above average (n=4, 50%) manner. Similarly, the
      majority of APPE students indicated the LLM prepared APPE students for practice
      in an excellent (n=3, 37.5%) or above average (n=5, 62.5%) manner. In addition,
      the following common themes developed, which highlight the benefits of the
      experience: reinforcement of knowledge through instruction, enhanced
      understanding of APPE expectations, exposure to multiple teaching styles, and
      creation of a comfortable learning environment. Students suggested the LLM
      include increased time for interaction with other learners. SUMMARY: An LLM
      involving P3 IPPE and P4 APPE pharmacy students, in an ambulatory care practice
      setting, was associated with positive student perceptions. Student feedback was
      best utilized to generate the hypothesis that this LLM may increase both APPE and
      practice readiness. However, further study is needed to confirm direct cause and
      effect.

PMID- 30236429
TI  - What do I eat? Impact of an interactive teaching method for improving pharmacy
      students' diabetes nutrition knowledge and comfort in providing nutrition
      counseling.
AB  - BACKGROUND AND PURPOSE: Didactic approaches for instructing students about
      diabetes nutrition and self-management have been described previously in the
      pharmacy education literature. There is a need for diabetes nutrition active
      learning approaches that can be incorporated into the advanced pharmacy practice
      experience (APPE) setting so students can apply previous didactic learning in a
      real world setting. The goal was to add to students' knowledge of diabetes
      nutrition thereby increasing their comfort in discussing nutrition with patients.
      EDUCATIONAL ACTIVITY AND SETTING: The nutrition tour activity was implemented in
      the APPE setting and involved pharmacy students on ambulatory and inpatient
      rotations. The nutrition tour included several active learning exercises such as
      evaluation of nutrition labels and development of a day-long carbohydrate
      consistent meal plan to encourage student engagement and application of
      information. Student pre- and post-activity survey data was collected two weeks
      before and two weeks after the tour to assess retention of knowledge of diabetes
      nutrition and comfort in diabetes nutrition education. Changes in knowledge and
      comfort were assessed using t-tests. FINDINGS: Fifty-five pharmacy students
      participated in the nutrition tour with 45 completing the pre-activity survey and
      40 completing the post-activity survey. Comparison of student pre- and post
      activity survey scores identified statistically significant increases in both
      total nutrition knowledge (p < 0.001) and student comfort in counseling on
      diabetes nutrition (p < 0.001). DISCUSSION AND SUMMARY: A diabetes nutrition tour
      guided by a pharmacy preceptor for APPE students was associated with increased
      diabetes nutrition knowledge and comfort in educating on diabetes nutrition.

PMID- 30236431
TI  - Establishment of a patient-centered communication course to address curricular
      gaps.
AB  - BACKGROUND AND PURPOSE: Patient-centered communication (PCC) skills are critical
      to the practice of pharmacy. A gap analysis of the communication content of our
      curriculum revealed inadequate coverage of several competencies recommended by a
      National Association of Chain Drug Stores Foundation - National Community
      Pharmacy Association - Accreditation Council for Pharmacy Education joint task
      force report: "support patient behavior change through skills such as
      motivational interviewing", "demonstrate compassion and empathy for patients",
      and "solve adherence challenges created by low health literacy". EDUCATIONAL
      ACTIVITY AND SETTING: A required PCC course, heavily grounded in motivational
      interviewing principles, was introduced into the spring of the first professional
      year to address the identified curricular gaps. Activities and assessments in
      additional semesters were added to further develop these skills and provide
      accountability. FINDINGS: The course addressed the curricular gaps and was well
      received by students. Students demonstrated competency in a role-play setting
      including improved proficiency between role-play activities. Reflections from a
      community pharmacy introductory pharmacy practice experience (IPPE) demonstrate
      that students perceived an ability to use the skills in practice. DISCUSSION AND
      SUMMARY: This course has been successfully established as an introduction to PCC
      concepts and skills for first professional year pharmacy students. Use of the
      skills during a community pharmacy IPPE illustrates that the class functions as a
      foundation on which to further develop these skills throughout the remaining
      didactic and experiential curricula.

PMID- 30236432
TI  - Describing pharmacy student participation in an international, interprofessional
      medical mission trip as part of an advanced pharmacy practice experience (APPE).
AB  - BACKGROUND AND PURPOSE: Several schools of pharmacy across the United States have
      taken steps to incorporate international medical mission trips into the doctor of
      pharmacy (PharmD) curriculum. This study aims to describe the impact of advanced
      pharmacy practice experience (APPE)-level student pharmacists on an
      interprofessional team during an international medical mission trip to Jamaica.
      EDUCATIONAL ACTIVITY AND SETTING: The Jamaica Medical Mission (JMM) trip is an
      annual event involving healthcare professionals from several disciplines across
      multiple universities and healthcare systems. At this institution, the JMM trip
      is included as part of a rural health elective APPE rotation. Students electing
      to participate in this rotation are provided with the opportunity to serve as
      active participants on an interprofessional healthcare team in underserved and
      under-resourced communities throughout Jamaica. The JMM trip that took place
      during June 2016 included healthcare professionals and students in the fields of
      medicine, dentistry, optometry, nursing, and pharmacy. A total of five pharmacist
      preceptors and 10 pharmacy students attended the JMM trip in June 2016.
      Approximately three to five clinic sites per day were conducted simultaneously on
      each of the seven clinic days at various locations throughout Jamaica. The
      interprofessional healthcare teams provided free medical care, including physical
      exams and access to prescription and non-prescription medications. FINDINGS: The
      interprofessional healthcare team saw a total of 1014 patients and dispensed 1879
      prescriptions during the seven clinic days. A total of 811 clinical
      recommendations were made by student pharmacists and/or pharmacy preceptors. Of
      these recommendations, 561 (69%) were made by student pharmacists without
      pharmacy preceptor prompting, 103 (13%) were made by the student pharmacist with
      preceptor prompting, and 147 (18%) were made by pharmacy preceptors. Over 70% of
      recommendations made by student pharmacists without pharmacy preceptor prompting
      were accepted by prescribers. DISCUSSION AND SUMMARY: This study sought to
      describe the impact of APPE-level student pharmacists on an interprofessional
      team during an international medical mission trip. Our findings demonstrate that
      APPE-level student pharmacists were capable of making a substantial number of
      clinical recommendations without preceptor prompting. The number of
      recommendations made by students without preceptor prompting were consistently
      greater than the number of recommendations made with preceptor prompting
      throughout the trip. Future studies should address student competence in
      achieving learning objectives associated with international, interprofessional
      APPE rotations.

PMID- 30236434
TI  - Comparison of pharmacy students' self-efficacy to address cessation counseling
      needs for traditional and electronic cigarette use.
AB  - BACKGROUND AND PURPOSE: This study assessed pharmacy students' self-rated ability
      to provide cessation counseling for e-cigarette use and traditional cigarette
      smoking. EDUCATIONAL ACTIVITY AND SETTING: A cross-sectional study was conducted
      in spring 2014 at The University of Texas at Austin. Participants included first
      through fourth year (P1-P4) doctor of pharmacy (PharmD) students. Perceived
      confidence and knowledge to counsel on cigarette smoking cessation and e
      cigarette cessation were self-rated and based on the Ask-Advise-Assess-Assist-and
      Arrange (5 A's) follow-up model as well as general counseling skills for
      recreational nicotine product use cessation. Comparisons were made between
      students' confidence to counsel patients on traditional cigarette smoking
      cessation and e-cigarette cessation and by class level. FINDINGS: Compared to
      cigarette smoking cessation counseling, students were less confident in their
      ability to counsel on e-cigarette cessation using the 5 A's model and general
      counseling skills. Students perceived themselves to be less knowledgeable about
      the harmful effects of e-cigarettes, pharmacists' role in counseling on e
      cigarette cessation, and how patients can benefit from e-cigarette cessation
      counseling. A higher proportion of students reported having no training on e
      cigarette cessation compared to cigarette smoking cessation (59% vs 9%). SUMMARY:
      Targeted training on how to counsel patients on e-cigarette cessation should be
      included in pharmacy curricula. Such training is expected to increase the
      confidence of pharmacists-in-training to address the needs of patients who use e
      cigarettes.

PMID- 30236433
TI  - Integration of mentored self-directed learning (MSDL) through both group and
      individual presentations in an accelerated modified block program.
AB  - BACKGROUND AND PURPOSE: Project aim was to examine the feasibility and logistics
      of mentored self-directed learning (MSDL) through group and individual
      presentations in an accelerated modified block curriculum. Perspectives of
      students and faculty members toward the incorporation of MSDL were also explored.
      EDUCATIONAL ACTIVITY AND SETTING: During a two-week pharmacotherapy block,
      students made group presentations requiring two elements: a case presentation on
      curricular content (Element-1) and an inclusion of "novel" information students
      did not receive didactically (Element-2). Curricular content for Element-1
      stemmed from a pharmacotherapy course on gastroenterology and nutrition, and
      individual presentations were scheduled during a semester-long skill-based
      course. Surveys on student perspectives were conducted at baseline, after group
      presentations, and after individual presentations. Faculty members also provided
      feedback and evaluations. FINDINGS: Whereas 58% of students considered a case
      presentation (Element-1) more valuable for their learning than inclusion of
      Element-2, 78% of faculty's responses indicated the incorporation of both
      Elements was valuable. For the following individual presentations, 73% of
      students were willing and able to present a topic not extensively addressed in
      the didactic curriculum by employing MSDL. Students improved their confidence in
      preparing and making presentations for peers and faculty/preceptors through the
      MSDL activities (p < 0.025). At the end of this project, the faculty determined
      88% of students were ready to give a presentation considered appropriate for
      Advanced Pharmacy Practice Experience. DISCUSSION: MSDL through group and
      individual presentation activities were feasible and provided a valuable learning
      experience for students in an accelerated modified block curriculum.

PMID- 30236435
TI  - Self-paced online learning modules for pharmacy practice educators: Development
      and preliminary evaluation.
AB  - BACKGROUND AND PURPOSE: The purpose of this paper is to describe the development
      of a series of six, self-paced online practice educator development modules and
      to describe the preliminary program evaluation conducted for them. EDUCATIONAL
      ACTIVITY AND SETTING: Six online learning modules were developed. In the
      preliminary program evaluation, a mixed methods approach was used to investigate
      whether module content was effective in conveying useful information to practice
      educators and was reaching those at a geographic distance from the University of
      British Columbia (UBC) in Vancouver, Canada. User demographic data, module
      completion results, user evaluation survey responses, and content expert reviews
      of the modules were collected and analyzed for quality assurance and program
      evaluation. FINDINGS: The preliminary evaluation results indicated a positive
      response. The evaluation survey results showed that most practice educators found
      their understanding of the subject had increased from their personal baseline
      after completing the module. From the total of 197 users that had registered for
      the Practice Educator Resource Centre and self-declared their geographic
      location, 56% were categorized as being within the Lower Mainland, while 44% were
      located outside of this area, at a geographic distance from UBC. DISCUSSION: This
      early data indicated the modules were reaching practice educators across BC.
      Continual evaluation will be needed to support the preliminary positive practice
      educator user experience. SUMMARY: The self-paced online practice educator
      modules are an accessible and possibly effective means of providing skills and
      training to new and current pharmacy practice educators.

PMID- 30236436
TI  - Impact of an interprofessional medication error workshop on healthcare student
      perceptions.
AB  - BACKGROUND: The integration of interprofessional education (IPE) into health
      professional curricula is critical to ensuring safe and efficient delivery of
      patient care. The intent of this manuscript is to describe the results of a pilot
      study designed to evaluate the impact of a large-scale interprofessional
      medication error prevention workshop on student perceptions of team-based patient
      care in the prevention of medication errors. INTERPROFESSIONAL EDUCATION
      ACTIVITY: Pharmacy, medical, and physician assistant students' perceptions of the
      role of multidisciplinary patient care teams in preventing medication errors were
      evaluated before and after participating in a three-hour interprofessional
      medication errors prevention workshop utilizing a modified version of the
      validated Attitudes Towards Health Care Teams Scale. DISCUSSION: When comparing
      student attitudes among the three schools, statistically significant differences
      in student perceptions across the items and subscales (e.g., quality of
      care/process and physician centrality) captured in the instrument utilized were
      identified. Additionally, differences in the responses of pharmacy, medical, and
      physician-assistant students were found, highlighting the areas where healthcare
      education can be targeted to bridge the gap in opinion. IMPLICATIONS: We
      demonstrated an overall positive impact of an interprofessional medication errors
      prevention-themed workshop on the attitudes of the participating healthcare
      students. Future directions and research initiatives focusing on the role of IPE
      and the influence of IPE workshops on team-based performance are indicated to
      validate the influence of this method of education on the attitudes of post
      graduate healthcare trainees and healthcare practitioners.

PMID- 30236235
TI  - Cancelled operations: a 7-day cohort study of planned adult inpatient surgery in
      245 UK National Health Service hospitals.
AB  - BACKGROUND: Cancellation of planned surgery impacts substantially on patients and
      health systems. This study describes the incidence and reasons for cancellation
      of inpatient surgery in the UK NHS. METHODS: We conducted a prospective
      observational cohort study over 7 consecutive days in March 2017 in 245 NHS
      hospitals. Occurrences and reasons for previous surgical cancellations were
      recorded. Using multilevel logistic regression, we identified patient- and
      hospital-level factors associated with cancellation due to inadequate bed
      capacity. RESULTS: We analysed data from 14 936 patients undergoing planned
      surgery. A total of 1499 patients (10.0%) reported previous cancellation for the
      same procedure; contemporaneous hospital census data indicated that 13.9%
      patients attending inpatient operations were cancelled on the day of surgery. Non
      clinical reasons, predominantly inadequate bed capacity, accounted for a large
      proportion of previous cancellations. Independent risk factors for cancellation
      due to inadequate bed capacity included requirement for postoperative critical
      care [odds ratio (OR)=2.92; 95% confidence interval (CI), 2.12-4.02; P<0.001] and
      the presence of an emergency department in the treating hospital (OR=4.18; 95%
      CI, 2.22-7.89; P<0.001). Patients undergoing cancer surgery (OR=0.32; 95% CI,
      0.22-0.46; P<0.001), obstetric procedures (OR=0.17; 95% CI, 0.08-0.32; P<0.001),
      and expedited surgery (OR=0.39; 95% CI, 0.27-0.56; P<0.001) were less likely to
      be cancelled. CONCLUSIONS: A significant proportion of patients presenting for
      surgery have experienced a previous cancellation for the same procedure. Cancer
      surgery is relatively protected, but bed capacity, including postoperative
      critical care requirements, are significant risk factors for previous
      cancellations.

PMID- 30236437
TI  - Using interprofessional medication management simulations to impact student
      attitudes toward teamwork to prevent medication errors.
AB  - BACKGROUND: We developed and implemented a project incorporating ACPE Standard 11
      and all Core IPEC competencies at a public University located at a medical
      center. The project was a collaboration between the colleges of nursing,
      pharmacy, and medicine at a distance campus location. INTERPROFESSIONAL EDUCATION
      ACTIVITY: Our Interprofessional Education Activity, which targeted all three
      elements of ACPE Standard 11, provided TeamSTEPPS(r) training followed by four
      medical error simulations. A debriefing took place after each scenario within a
      team as well as with all four groups following each simulation session. The
      Teamwork Attitudes Questionnaire (TTAQ) was used to evaluate the activity.
      DISCUSSION: Findings from our interprofessional education activity indicate that
      while students entered the activity already perceiving teamwork as a positive
      aspect of safe care delivery, significant improvement in attitudes post training
      toward specific team constructs was seen across all five domains. The project
      helped inform the structure of a replication of this effort that is currently
      underway, with a focus on embedding it in the curricula of all three programs
      (medicine, pharmacy, and nursing) across campuses. IMPLICATIONS: In summary,
      working collaboratively in a team while being exposed to a series of medication
      management scenarios enhances teamwork attitudes as well as potentially improving
      performance. Based on the positive initial results, plans have begun to extend
      the experience to other campuses and include a wider group of students.

PMID- 30236438
TI  - Development and implementation of an interprofessional pharmacotherapy learning
      experience during an advanced pharmacy practice rotation in primary care.
AB  - BACKGROUND: There is increased focus and pressure to include interprofessional
      education during training of health professionals. This program describes an
      interprofessional education program between pharmacy, medical, and nurse
      practitioner students during a primary care clinical rotation elective.
      INTERPROFESSIONAL EDUCATION ACTIVITY: The interprofessional education program
      (IPE) during a primary care rotation was developed to be included as a learning
      experience throughout the rotation period. The health professions included have a
      role in appropriate prescribing; therefore, the content emphasis is primary care
      disease states where pharmacotherapy is a treatment modality. DISCUSSION: Data
      assessing the program was collected using the Interprofessional Education
      Perception Scale (IEPS) from April 2014 to April 2016. A total of 56 IEPS pre-
      and post-surveys were collected for analysis. A significant difference in the
      IEPS scale was found in the subgroups of (1) professional competence and autonomy
      and (2) perceived need for professional competence (p < .05). Qualitative results
      of the completed surveys show a trend of respectful and positive communication
      between students, lack of previous IPE experience prior to the intervention, and
      a collaborative environment where students had the opportunity to learn about
      each other's professions. Structured interactions between health professions
      student interactions during clinical rotations can be beneficial for students to
      learn about each other and may lead to better collaboration. The authors will use
      the current program as a foundation for other interprofessional activities
      between students.

PMID- 30236439
TI  - Did Caravaggio die of Staphylococcus aureus sepsis?

PMID- 30236444
TI  - Impact of preoperative body mass index on postoperative co-morbidity remission in
      super-obese patients undergoing bariatric surgery.

PMID- 30236442
TI  - Lower Limb Deep Vein Diameters Beneath Medical Compression Stockings in the
      Standing Position.
AB  - OBJECTIVES: The mechanism by which compression therapy works is still discussed,
      especially at calf level. Whether lower limb deep vein diameters change under
      compression stockings is a matter of debate: no change versus great change. New
      study material helps to address this question. METHODS: This was an experimental
      single centre controlled study on nine selected patients with mild to moderate
      superficial venous disease. A total of 34 deep vein segments were examined. A new
      hybrid (elastic + non-elastic materials) cuff pressure device enabled the deep
      vein diameter changes from baseline to occlusion similar to that which could be
      observed under stockings. The deep vein diameters were measured through the
      device with the patients in a standing position and their body weight distributed
      equally on both legs. This was compared to a 20-35 mm Hg medical compression
      stocking. The diameter change when patients put their whole body weight on the
      tested leg was also measured. RESULTS: A pressure of 25.3 +/- 6.4 mm Hg (mean,
      SD) was required to ovalise lower leg deep veins and a pressure of 43.1 +/- 16.2
      mm Hg (mean, SD) to occlude them. Both pressures were significantly different
      from baseline: p = .003 and p < .0001, respectively. No diameter reduction was
      achieved when the stockings were worn, and occlusion of deep veins occurred when
      the patients transferred their body weight onto the examined leg. CONCLUSION: In
      the standing position, deep vein diameter reduction is not caused by compression
      stockings but may be due to the isometric muscle contractions required to support
      the patient's body weight.

PMID- 30236440
TI  - [Pulmonary tuberculosis: Radiological evolution of broncho-pulmonary lesions at
      the end of treatment].
AB  - OBJECTIVES: To describe the residual broncho-pulmonary lesions and evaluate the
      role of CT scanning at the end of treatment of pulmonary tuberculosis. MATERIALS
      AND METHODS: Analysis of the initial and end of treatment CT scans of 56 patients
      with pulmonary tuberculosis according to a reading grid including parenchymatous
      and airways lesions. The CT data at the end of treatment were analysed in
      relation to the clinical and microbiological data, and the original CT scan.
      RESULTS: Active lesions (thick walled cavities and/or centrilobular micronodules)
      persisted in 24 patients (43%) after a mean treatment period of 7 months. The
      persistence of these signs of activity was correlated with the initial presence
      of a cavitary syndrome (p=0.027), with predominant sub-segmentary bronchial
      involvement, with extensive micronodular spread (p=0.024) and with bronchiectasis
      (p=0.04). These residual lesions were not associated with an increased risk of
      relapse. CONCLUSION: The persistence of signs of activity on the CT scan at the
      end of treatment of tuberculosis do not necessarily correspond to an absence of
      cure but to a radiological delay. This imaging is nevertheless useful to make an
      assessment of any subsequent changes in the bronchial tree and to estimate the
      risk of later complications.

PMID- 30236443
TI  - Roux-en-Y gastric bypass, sleeve gastrectomy, or one anastomosis gastric bypass
      as rescue therapy after failed adjustable gastric banding: a multicenter
      comparative study.
AB  - BACKGROUND: To date, laparoscopic adjustable gastric banding remains the third
      most commonly performed surgical procedure for weight loss. Some patients fail to
      get acceptable outcomes and undergo revisional surgery at rates ranging from 7%
      to 60%. Roux-en-Y gastric bypass (RYGB), one anastomosis gastric bypass (OAGB),
      and sleeve gastrectomy (SG) are among the most common salvage options for failed
      laparoscopic adjustable gastric banding. OBJECTIVE: To compare the outcomes of
      converting failed laparoscopic adjustable gastric banding to RYGB, OAGB, or SG.
      METHODS: Data collected from 7 experienced bariatric centers around the world
      were retrospectively collected, reviewed, and analyzed. Final body mass index
      (BMI), change in BMI, percentage excess BMI loss, and major complications with
      particular attention to leaks, hemorrhage, and mortality were reported. RESULTS:
      Of 1219 patients analyzed, 74% underwent RYGB, 16% underwent OAGB, and 10%
      underwent SG after banding failure. The mean age was 38 years (+/-10 yr), and 82%
      of patients were women. The mean follow-up was 33 months. The follow-up rate was
      100%, 87%, and 52% at 1, 3, and 5 years, respectively. At the latest follow-up,
      percentage excess BMI loss >50% was achieved by 75% of RYGB, 85% of OAGB, and 67%
      of SG patients. Postoperative complications occurred in 13% of patients after
      RYGB, 5% after OAGB, and 15% after SG. CONCLUSION: Our data show that it is
      possible to achieve or maintain significant weight loss with an acceptable
      complication rate with all 3 surgical options.

PMID- 30236441
TI  - Impact of Surgeon's Experience on Vascular and Haemorrhagic Complications After
      Kidney Transplantation.
AB  - OBJECTIVE: The aim of this study was to investigate the independent risk factors
      of vascular and haemorrhagic complications after kidney transplantation (KTx) and
      to evaluate how the surgeon's experience affects the rate of vascular and
      haemorrhagic complications. METHODS: After exclusion of paediatric and multi
      organ transplantations, 1462 KTx operations between 2000 and 2016 were analysed.
      Independent risk factors were evaluated by multivariable logistic regression
      analysis. The generalised estimating equation logit model was used to display
      learning curve progression and determine the best cut off number of KTx
      operations to reduce vascular and haemorrhagic complications. RESULTS: Vascular
      and haemorrhagic complications occurred in 38 KTx cases (2.6%). Renal vein
      thrombosis was the most common complication (0.6%). Graft loss occurred in 11 of
      38 (28.9%) cases. Donor age of >60 years (OR 3.687, 95% CI 1.663-8.175, p =
      0.001), recipient cardiovascular disease (CVD) (OR 2.270, 95% CI 1.071-4.810, p =
      0.032), and surgeon's experience (OR 0.875, 95% CI 0.783-0.977, p = 0.018) were
      independent predictors of vascular and haemorrhagic complications. Twenty-six
      previous KTx operations are needed to decrease predicted probability of post-KTx
      vascular and haemorrhagic complications below 2.6%. CONCLUSIONS: The surgeon's
      experience is an independent risk factor for vascular and haemorrhagic
      complications after KTx. Acceptable post-operative vascular and haemorrhagic
      complications are achieved after a minimum of 26 KTx. As a donor age of >60 years
      and recipient CVD are also independent risk factors for vascular and haemorrhagic
      complications, it is suggested that these patients should preferably be operated
      on by surgeons who have performed more than 26 KTx operations.

PMID- 30236445
TI  - Transcriptome profiling of the cardiac neural crest reveals a critical role for
      MafB.
AB  - The cardiac neural crest originates in the caudal hindbrain, migrates to the
      heart, and contributes to septation of the cardiac outflow tract and ventricles,
      an ability unique to this neural crest subpopulation. Here we have used a FoxD3
      neural crest enhancer to isolate a pure population of cardiac neural crest cells
      for transcriptome analysis. This has led to the identification of transcription
      factors, signaling receptors/ligands, and cell adhesion molecules upregulated in
      the early migrating cardiac neural crest. We then functionally tested the role of
      one of the upregulated transcription factors, MafB, and found that it acts as a
      regulator of Sox10 expression specifically in the cardiac neural crest. Our
      results not only reveal the genome-wide profile of early migrating cardiac neural
      crest cells, but also provide molecular insight into what makes the cardiac
      neural crest unique.

PMID- 30236446
TI  - TMED2/emp24 is required in both the chorion and the allantois for placental
      labyrinth layer development.
AB  - TMED2, a member of the transmembrane emp24 domain (TMED) family, is required for
      transport of cargo proteins between the ER and Golgi. TMED2 is also important for
      normal morphogenesis of mouse embryos and their associated placenta, and in fact
      Tmed2 homozygous mutant embryos arrest at mid-gestation due to a failure of
      placental labyrinth layer formation. Differentiation of the placental labyrinth
      layer depends on chorioallantoic attachment (contact between the chorion and
      allantois), and branching morphogenesis (mingling of cells from these two
      tissues). Since Tmed2 mRNA was found in both the chorion and allantois, and 50%
      of Tmed2 homozygous mutant embryos failed to undergo chorioallantoic attachment,
      the tissue-specific requirement of Tmed2 during placental labyrinth layer
      formation remained a mystery. Herein, we report differential localization of
      TMED2 protein in the chorion and allantois, abnormal ER retention of Fibronectin
      in Tmed2 homozygous mutant allantoises and cell-autonomous requirement for Tmed2
      in the chorion for chorioallantoic attachment and fusion. Using an ex vivo model
      of explanted chorions and allantoises, we showed that chorioallantoic attachment
      failed to occur in 50% of samples when homozygous mutant chorions were recombined
      with wild type allantoises. Furthermore, though expression of genes associated
      with trophoblast differentiation was maintained in Tmed2 mutant chorions with
      chorioallantoic attachment, expression of these genes was attenuated. In
      addition, Tmed2 homozygous mutant allantoises could undergo branching
      morphogenesis, however the region of mixing between mutant and wild type cells
      was reduced, and expression of genes associated with trophoblast differentiation
      was also attenuated. Our data also suggest that Fibronectin is a cargo protein of
      TMED2 and indicates that Tmed2 is required cell-autonomously and non-autonomously
      in the chorion and the allantois for placental labyrinth layer formation.

PMID- 30236447
TI  - Micromotors for drug delivery in vivo: The road ahead.
AB  - Autonomously propelled/externally guided micromotors overcome current drug
      delivery challenges by providing (a) higher drug loading capacity, (b) localized
      delivery (less toxicity), (c) enhanced tissue penetration and (d) active
      maneuvering in vivo. These microscale drug delivery systems can exploit
      biological fluids, as well as exogenous stimuli, like light-NIR, ultrasound and
      magnetic fields (or a combination of these), towards propulsion/drug release.
      Ability of these wireless drug carriers towards localized targeting and
      controlled drug release, makes them a lucrative candidate for drug administration
      in complex microenvironments (like solid tumors or gastrointestinal tract). In
      this report, we discuss these microscale drug delivery systems for their
      therapeutic benefits under in vivo setting and provide a design-application
      rationale towards greater clinical significance. Also, a proof-of-concept
      depicting 'microbots-in-a-capsule' towards oral drug delivery has been discussed.

PMID- 30236448
TI  - Brain changes in social anxiety disorder run in the family.

PMID- 30236449
TI  - Retinoic acid signaling balances adult distal lung epithelial progenitor cell
      growth and differentiation.
AB  - BACKGROUND: Despite compelling data describing pro-regenerative effects of all
      trans retinoic acid (ATRA) in pre-clinical models of chronic obstructive
      pulmonary disease (COPD), clinical trials using retinoids for emphysema patients
      have failed. Crucial information about the specific role of RA signaling in adult
      rodent and human lung epithelial progenitor cells is largely missing. METHODS:
      Adult lung organoid cultures were generated from isolated primary mouse and human
      lung epithelial cells, and incubated with pharmacological pathway modulators and
      recombinant proteins. Organoid number and size were measured, and differentiation
      was assessed with quantitative immunofluorescence and gene expression analyses.
      FINDINGS: We unexpectedly found that ATRA decreased lung organoid size, whereas
      RA pathway inhibition increased mouse and human lung organoid size. RA pathway
      inhibition stimulated mouse lung epithelial proliferation via YAP pathway
      activation and epithelial-mesenchymal FGF signaling, while concomitantly
      suppressing alveolar and airway differentiation. HDAC inhibition rescued
      differentiation in growth-augmented lung organoids. INTERPRETATION: In contrast
      to prevailing notions, our study suggests that regenerative pharmacology using
      transient RA pathway inhibition followed by HDAC inhibition might hold promise to
      promote lung epithelial regeneration in diseased adult lung tissue. FUND: This
      project is funded by the Lung Foundation Netherlands (Longfonds) grant 6.1.14.009
      (RG, MK, JS, PSH) and W2/W3 Professorship Award by the Helmholtz Association,
      Berlin, Germany (MK).

PMID- 30236450
TI  - Contemporary update of overall prognosis and nomogram to predict individualized
      survival for Chinese patients with eyelid sebaceous carcinoma.
AB  - BACKGROUND: The prognosis of Chinese patients with eyelid sebaceous carcinoma
      (SC) has not been updated for >3 decades. The prognostic predictors are
      multifactorial, and there is no validated prognostic model for eyelid SC.
      METHODS: This study included 238 consecutive patients with eyelid SC. All
      eligible patients were followed up for metastasis and mortality. The predictors
      of tumor-related survival were explored by Cox analyses. A prognostic nomogram
      was developed and validated using bootstrap resampling. The predictive accuracy
      and discriminative ability were compared between the nomogram and the Tumor,
      Node, Metastasis (TNM) staging system. FINDINGS: After a median follow-up period
      of 55.5 months, 27 (11.3%) patients died of metastatic SC, with a median survival
      time of 48.0 months. The 5-year and 10-year tumor-related survival rates were
      88.1% and 77.9%, respectively. Orbital involvement (HR: 3.11, p = .022), the
      greatest tumor basal diameter (HR: 1.06, p = .003), the presence of pagetoid
      spread (HR: 2.90, p = .017), and having lymph node metastasis at initial
      diagnosis (HR: 13.66, p < .001) were independent risk factors for tumor-related
      death. A nomogram integrating these 4 factors was developed with a C-index of
      0.887, which is significantly better than that of the TNM staging system (p =
      .002). The risk groups stratified by nomogram scores (p < .001 (low vs
      intermediate risk); p = .001 (intermediate vs high risk)) displayed better
      discrimination ability than TNM staging (T1 vs T2: p = .358; T2 vs T3: p = .171;
      T3 vs T4: p < .001) in patients at an early stage. INTERPRETATION: The prognosis
      of Chinese patients with eyelid SC has improved over the last 3 decades, and it
      is comparable to that of patients from other countries. This nomogram provides
      more accurate individualized estimates of survival for eyelid SC patients and may
      guide clinicians in their therapeutic decisions.

PMID- 30236452
TI  - Behcet's Syndrome: Fear Not the Unknown.

PMID- 30236453
TI  - A novel role for zinc transporter 8 in the facilitation of zinc accumulation and
      regulation of testosterone synthesis in Leydig cells of human and mouse
      testicles.
AB  - OBJECTIVE: Zinc is intimately involved in testosterone production. Zinc
      transporter 8 (ZnT8) is found to be localized in insulin secretory granules as a
      beta-cell specific Zn transporter. The effect of ZnT8 and related zinc
      accumulation in steroidogenesis, however, is still unknown. The present study
      aimed to explore whether ZnT8 plays a role in the facilitation of zinc
      accumulation and regulation of testosterone synthesis in testicles. METHODS:
      Leydig cells were isolated from the testicles of human, CD-1 suckling and ZnT8-KO
      mice. Zn accumulation in mitochondria was induced by hCG stimulation.
      Transfection of hZnT8-EGFP and RNA interfere of mZnT8 were done in MLTC-1 cells.
      ZnT8 expression and its co-localization with steroidogenic acute regulatory
      (StAR) protein were analyzed with RT-PCR, Western blot and dual-fluorescent
      staining protocols. Serum testosterone levels in mice were determined with
      chemiluminescent enzyme immunoassay. RESULTS: ZnT8 was found to be presented in
      Leydig cells and up-regulated in suckling mouse Leydig cells and MLTC-1 cells
      after hCG administration, by which zinc accumulation occurred in mitochondria.
      ZnT8 gene silencing or knockout inhibited stimulated progesterone and
      testosterone production, reduced stimulated zinc accumulation and down-regulated
      phosphorylated steroidogenic acute regulatory (StAR) expression in Leydig cells.
      Furthermore, an inhibitor (H89) of PKA blocked hCG-stimulated progesterone caused
      by ZnT8 over-expression and zinc treatment. CONCLUSION: The present study
      provided the first evidence that ZnT8 transports Zn into Leydig cell mitochondria
      with gonadotropin stimulation and suggests that ZnT8 may play a role in
      testosterone production via the PKA signaling pathway.

PMID- 30236454
TI  - Integrative cytological analysis of the effects of Ca2+ and vitamin D3 on
      extracellular Ca2+ flux and intracellular Ca2+ reserves in the mantle of the
      pearl oyster (Hyriopsis cumingii Lea).
AB  - To examine Ca2+ absorption and transportation in the freshwater pearl oyster,
      Hyriopsis cumingii Lea, we studied the effects of different levels of either
      extracellular Ca2+ or 1,25(OH)2D3 on extracellular Ca2+ flux and intracellular
      Ca2+ concentrations in mantle cells using the non-invasive micro-test technique
      and laser scanning confocal microscopy. The inner and outer mantle (IM and OM)
      cells from mussels were cultured and then treated with different concentrations
      of Ca2+ and 1,25(OH)2D3. Extracellular Ca2+ flux and intracellular Ca2+ reserves
      were analyzed. The results showed that both extracellular Ca2+ and 1,25(OH)2D3
      had significant effects on Ca2+ flux and reserves in mantle cells, especially in
      IM cells (P < .05). The increase in extracellular Ca2+ concentrations resulted in
      the conversion of extracellular Ca2+ flux into influx with an increase in flow
      rate (P < .05). The calcium ion fluorescence intensity of OM cells was higher
      than that of IM cells (P < .05). 1,25(OH)2D3 addition also significantly
      increased the influx rate of extracellular Ca2+, especially in IM cells, which
      were more sensitive to 1,25(OH)2D3 addition and had significantly higher Ca2+
      influx rates than did OM cells (P < .05). Fluorescence intensities of
      intracellular Ca2+ first increased and then decreased with increasing 1,25(OH)2D3
      levels. The study showed that IM cells play an important role in absorbing Ca2+
      from the environment, while OM cells mainly function in the temporary storage and
      transportation of Ca2+ in the body. The current results suggested that high
      levels of extracellular Ca2+ (1.25 mM) or 1,25(OH)2D3 (over 100 IU/L) were
      favorable for Ca2+ uptake and maintenance in the body.

PMID- 30236455
TI  - Issues in amiodarone-induced thyrotoxicosis: Update and review of the literature.
AB  - Amiodarone, a benzofuranic iodine-rich pan-anti-arrhythmic drug, induces
      amiodarone-induced thyrotoxicosis (AIT) in 7-15% of patients. AIT is a major
      issue due to its typical severity and resistance to anti-thyroid measures, and to
      its negative impact on cardiac status. Classically, AIT is either an iodine
      induced thyrotoxicosis in patients with abnormal thyroid (type 1), or due to
      acute thyroiditis in a "healthy" thyroid (type 2). Determination of the type of
      AIT is a diagnostic dilemma, as characteristics of both types may be present in
      some patients. As it is the main etiological factor in AIT, it is recommended
      that amiodarone treatment should be stopped; however, it may be the only anti
      arrhythmic option, needing to be either continued or re-introduced to improve
      cardiovascular survival. Recently, a few studies demonstrated that amiodarone
      could be continued or re-introduced in patients with history of type-2 AIT.
      However, in the other patients, it is recommended that amiodarone treatment be
      interrupted, to improve response to thioamides and to alleviate the risk of AIT
      recurrence. In such patients, thyroidectomy is recommended once AIT is under
      control, allowing safe re-introduction of amiodarone.

PMID- 30236451
TI  - Cholangiopathies - Towards a molecular understanding.
AB  - Liver diseases constitute an important medical problem, and a number of these
      diseases, termed cholangiopathies, affect the biliary system of the liver. In
      this review, we describe the current understanding of the causes of
      cholangiopathies, which can be genetic, viral or environmental, and the few
      treatment options that are currently available beyond liver transplantation. We
      then discuss recent rapid progress in a number of areas relevant for decoding the
      disease mechanisms for cholangiopathies. This includes novel data from analysis
      of transgenic mouse models and organoid systems, and we outline how this
      information can be used for disease modeling and potential development of novel
      therapy concepts. We also describe recent advances in genomic and transcriptomic
      analyses and the importance of such studies for improving diagnosis and
      determining whether certain cholangiopathies should be viewed as distinct or
      overlapping disease entities.

PMID- 30236456
TI  - UCP1 transrepression in Brown Fat in vivo and mineralocorticoid receptor anti
      thermogenic effects.
AB  - OBJECTIVES: The mineralocorticoid receptor (MR), a hormone-activated
      transcription factor, besides its role in controlling hydroelectrolytic
      homeostasis, exerts pro-adipogenic and anti-thermogenic effects, inhibiting
      mitochondrial-uncoupling protein UCP1 expression in brown adipocytes. The aim of
      this study was to gain insight into the molecular mechanisms by which MR
      participates in such metabolic regulation. METHODS: We evaluated in vivo MR
      effects on cold-induced UCP1 expression in MR-overexpressing mice. Expression
      profiles of several transcriptional coregulators were analyzed during
      differentiation of the brown adipocyte T37i cell line. Given that UCP1 expression
      is inversely controlled by catecholamines/retinoic acid and corticosteroids, we
      investigated the mechanisms of MR's inhibitory effect on UCP1 transcription in
      T37i cells. Chromatin immunoprecipitation (ChIP) experiments enabled us to
      explore MR interaction with UCP1 promoter regions. RESULTS: Cold-induced UCP1
      expression was blunted in the brown fat of MR-overexpressing mice. Along with
      induction of increasing mRNA levels for specific adipocyte markers during T37i
      differentiation, MR coactivator transcript levels significantly increased in
      intermediate states of differentiation, whereas expression of MR corepressors
      transiently increased approximately 2-fold. Such a simultaneous transient peak in
      coregulator expression is consistent with physiologically relevant cooperation
      occurring during brown adipogenesis. ChIP demonstrated that, after retinoic acid
      stimulation and aldosterone exposure, MR and PPARgamma concomitantly bind to
      specific UCP1 promoter motifs. CONCLUSION: Our studies demonstrate that MR exerts
      a pivotal metabolic role by controlling energy expenditure, and provide novel
      information on how MR participates in the regulation of brown adipocyte function.

PMID- 30236457
TI  - Thoracotomy and esophageal surgery: Key points to preserve the possibilities of
      flaps.
AB  - Anastomotic leakage frequently complicates esophagectomy and can trigger a rare
      life- threatening complication, a tracheoesophageal fistula. No guideline has yet
      addressed this complication. Plastic surgeons play a crucial role for salvage
      surgery. When a re-operation is chosen the possibilities of flap interposition
      depend on how the thoracotomy was initially performed. This study tried to
      identify key techniques in order help thoracic or general surgeons to preserve
      all the local flaps available for TEF if it occurs. These techniques improve flap
      conservation, helping plastic surgeons when a later transposition flap is
      required.

PMID- 30236458
TI  - Trends in the utilization and in-hospital outcomes when using mechanical
      circulatory support devices for stable chronic total occlusion treated with
      percutaneous coronary intervention.

PMID- 30236459
TI  - Five-year exposure to PM2.5 and ozone and subclinical atherosclerosis in late
      midlife women: The Study of Women's Health Across the Nation.
AB  - INTRODUCTION: Effects of more than one-year exposure to air pollution on
      atherosclerosis is seldom studied. This paper aims to examine the association
      between five-year exposure to particulate matter <=2.5 MUm (PM2.5), ozone (O3)
      and atherosclerosis observed about seven years later in late midlife women.
      MATERIAL AND METHODS: This study was conducted among 1188 women of the Study of
      Women's Health Across the Nation (SWAN) from five sites, Detroit, MI; Oakland,
      CA; Pittsburgh, PA; Chicago, IL; and Newark, NJ, with available data on both air
      pollutant exposure and carotid ultrasound scans. Five-year mean annualized
      exposure levels of two air pollutants, PM2.5 and ozone (O3), were collected
      during 5 SWAN visits (1999-2005) from monitors 20 km within the participant's
      residential address. Linear regression models were used to estimate the
      association of prior five-year mean annualized exposure to PM2.5 and O3 with
      common carotid intima-media thickness (cIMT) and inter-adventitial diameter (IAD)
      examined approximately seven years later (2009-2013). Logistic and multinomial
      logistic regressions were applied to assess the associations of air pollutants
      with plaque presence and plaque index, respectively. RESULTS: At time of carotid
      ultrasound scan, women were on average 59.6 (+/-2.7) years old and a majority was
      postmenopausal (88.4%). The women were White (48.4%), Black (31.2%), Chinese
      (13.3%) and Hispanic (7.1%). A 1 MUg/m3 higher 5-year mean annualized exposure to
      PM2.5 was associated with an 8.0 MUm (95% CI: 1.0-15.1) greater maximum cIMT at a
      later mid-life, adjusting for cardiovascular disease risk factors; but was only
      related to IAD after adjusting for site. No association was found between either
      pollutant and plaque presence or plaque index. CONCLUSIONS: Long-term exposure to
      PM2.5 may contribute to elevated risk of atherosclerosis in the post-menopausal
      period.

PMID- 30236461
TI  - Craniofacial polyostotic fibrous dysplasia: imaging findings.

PMID- 30236460
TI  - Functional imaging in pancreatic disease.
AB  - In addition to the classical morphological evaluation of pancreatic disease, the
      constant technological advances in imaging techniques based fundamentally on
      computed tomography and magnetic resonance imaging have enabled the quantitative
      functional and molecular evaluation of this organ. In many cases, this imaging
      based information results in substantial changes to patient management and can be
      a fundamental tool for the development of biomarkers. The aim of this article is
      to review the role of emerging functional and molecular techniques based on
      computed tomography and magnetic resonance imaging in the evaluation of
      pancreatic disease.

PMID- 30236462
TI  - Development of the human bladder and ureterovesical junction.
AB  - The urinary bladder collects urine from the kidneys and stores it until the
      appropriate moment for voiding. The trigone and ureterovesical junctions are key
      to bladder function, by allowing one-way passage of urine into the bladder
      without obstruction. Embryological development of these structures has been
      studied in multiple animal models as well as humans. In this report we review the
      existing literature on bladder development and cellular signalling with
      particular focus on bladder development in humans. The bladder and ureterovesical
      junction form primarily during the fourth to eighth weeks of gestation, and arise
      from the primitive urogenital sinus following subdivision of the cloaca. The
      bladder develops through mesenchymal-epithelial interactions between the endoderm
      of the urogenital sinus and mesodermal mesenchyme. Key signalling factors in
      bladder development include shh, TGF-beta, Bmp4, and Fgfr2. A concentration
      gradient of shh is particularly important in development of bladder musculature,
      which is vital to bladder function. The ureterovesical junction forms from the
      interaction between the Wolffian duct and the bladder. The ureteric bud arises
      from the Wolffian duct and is incorporated into the developing bladder at the
      trigone. It was previously thought that the trigonal musculature developed
      primarily from the Wolffian duct, but it has been shown to develop primarily from
      bladder mesenchyme. Following emergence of the ureters from the Wolffian ducts,
      extensive epithelial remodelling brings the ureters to their final trigonal
      positions via vitamin A-induced apoptosis. Perturbation of this process is
      implicated in clinical obstruction or urine reflux. Congenital malformations
      include ureteric duplication and bladder exstrophy.

PMID- 30236465
TI  - In reply.

PMID- 30236464
TI  - Identification of the epidural space with all the bells and whistles.

PMID- 30236466
TI  - The relative roles of sorption and biodegradation in the removal of contaminants
      of emerging concern (CECs) in GAC-sand biofilters.
AB  - The removal and fate of contaminants of emerging concern (CECs) in water
      treatment systems is of interest given the widespread occurrence of CECs in water
      supplies and increase in direct potable reuse of wastewater. In this study, CEC
      removal was investigated in pilot-scale biologically-active granular activated
      carbon (GAC)-sand and anthracite-sand filters under different hydraulic loading
      rates and influent CEC concentrations over a 15-month period. Eight of the most
      commonly detected compounds in a survey of CEC occurrence in drinking water were
      selected for this study: atenolol, atrazine, carbamazepine, fluoxetine,
      gemfibrozil, metolachlor, sulfamethoxazole and tris(2-chloroethyl) phosphate
      (TCEP). GAC-sand biofilters provided superior CEC removal for all compounds (mean
      removal efficiencies: 49.1-94.4%) compared to anthracite-sand biofilters (mean
      removal efficiencies: 0-66.1%) due to a combination of adsorption and
      biodegradation. Adsorption was determined to be the dominant removal mechanism
      for most selected CECs, except fluoxetine, which had the greatest biodegradation
      rate constant (0.93 +/- 0.15 min-1 at 20-28  degrees C). The mean removal
      efficiency decreased by 16.5% when the loading rate increased from 2 to 4 gpm/ft2
      (4.88-9.76 m/h). A significant reduction in CEC removal was observed after
      100,000 bed volumes when the influent CEC concentration was low (100-200 ng/L),
      whereas no significant reduction was observed during spike dosing (1000-3000
      ng/L). A regression analysis suggested that biodegradation rate, hydraulic
      loading rate, influent CEC concentration, throughput, influent dissolved organic
      carbon (DOC) concentration, and CEC charge are important parameters for
      predicting CEC removal performance in GAC-sand biofilters.

PMID- 30236463
TI  - Development of the human female reproductive tract.
AB  - Development of the human female reproductive tract is reviewed from the
      ambisexual stage to advanced development of the uterine tube, uterine corpus,
      uterine cervix and vagina at 22 weeks. Historically this topic has been under
      represented in the literature, and for the most part is based upon hematoxylin
      and eosin stained sections. Recent immunohistochemical studies for PAX2 (reactive
      with Mullerian epithelium) and FOXA1 (reactive with urogenital sinus epithelium
      and its known pelvic derivatives) shed light on an age-old debate on the
      derivation of vaginal epithelium supporting the idea that human vaginal
      epithelium derives solely from urogenital sinus epithelium. Aside for the vagina,
      most of the female reproductive tract is derived from the Mullerian ducts, which
      fuse in the midline to form the uterovaginal canal, the precursor of uterine
      corpus and uterine cervix an important player in vaginal development as well.
      Epithelial and mesenchymal differentiation markers are described during human
      female reproductive tract development (keratins, homeobox proteins (HOXA11 and
      ISL1), steroid receptors (estrogen receptor alpha and progesterone receptor),
      transcription factors and signaling molecules (TP63 and RUNX1), which are
      expressed in a temporally and spatially dynamic fashion. The utility of
      xenografts and epithelial-mesenchymal tissue recombination studies are reviewed.

PMID- 30236467
TI  - Nanofiltration performances after membrane bioreactor for hospital wastewater
      treatment: Fouling mechanisms and the quantitative link between stable fluxes and
      the water matrix.
AB  - Treatment combining membrane bioreactors (MBR) and nanofiltration (NF) is
      becoming an emerging wastewater treatment strategy. The combined process is
      capable of producing high quality water potentially reusable; however, diverse
      compositions of MBR effluents induce several types and degrees of NF membrane
      fouling that impacts process productivity. Moreover, since MBR effluent
      composition for one type of wastewater source is variable depending on the MBR
      efficiency at different periods, downstream NF membrane fouling types and degrees
      may consequently change over time. In that context, the present paper aims at
      developing effective fouling control strategies of NF membrane in the case of the
      filtration of MBR effluents taken from a MBR system installed in a French
      hospital. These effluents were filtrated under various transmembrane pressures,
      and stable fluxes during these filtrations were determined. Several types and
      degrees of fouling mechanisms were then identified through surface morphology
      observation and the analysis of chemical compositions of fouled membranes. The
      diverse flux behaviour was further associated with the fouling mechanisms and
      foulant compositions. Based on the study of these mechanisms, the quantitative
      link between stable fluxes and calcium phosphate concentrations in MBR effluents
      has been established.

PMID- 30236468
TI  - Successful restoration of a tropical shallow eutrophic lake: Strong bottom-up but
      weak top-down effects recorded.
AB  - Fish manipulation has been used to restore lakes in the temperate zone. Often
      strong short-term cascading effects have been obtained, but the long term
      perspectives are less clear. Fish manipulation methods are far less advanced for
      warm lakes, and it is debatable whether it is, in fact, possible to create a
      trophic cascade in warm lakes due to the dominance and high densities of fast
      reproducing omnivorous fish. However, removal of benthic feeding fish also reduce
      disturbance of the sediment, which not only affects the nutrient level but also
      the concentration of suspended organic and inorganic matter with enhanced water
      clarity and potentially better growth conditions for submerged macrophytes. We
      conducted a biomanipulation experiment in one of the basins in Chinese Huizhou
      West Lake that have remained highly turbid after extensive nutrient loading
      reduction. Another basin was used as control (control-treatment pairing design).
      Removal of a substantial amount of plankti-benthivorous fish was followed by
      planting of submerged macrophytes and stocking of piscivorous fish. We found
      strong and relatively long-lasting effects of the restoration initiative in the
      form of substantial improvements in water clarity and major reductions in
      nutrient concentrations, particularly total phosphorus, phytoplankton and
      turbidity, while only minor effects were detected for crustacean zooplankton
      grazers occurring in low densities before as well as after the restoration. Our
      results add importantly to the existing knowledge of restoration of warm lakes
      and are strongly relevant, not least in Asia where natural lakes frequently are
      used extensively for fish production, often involving massive stocking of
      benthivorous fish. With a growing economy and development of more efficient fish
      production systems, the interest in restoring lakes is increasing world-wide. We
      found convincing evidence that fish removal and piscivores stocking combined with
      transplantation of submerged macrophytes may have significant effects on water
      clarity in warm shallow lakes even if the zooplankton grazing potential remains
      low, the latter most likely as a result of high predation on the zooplankton.

PMID- 30236469
TI  - Interactions between polybrominated diphenyl ethers (PBDEs) and TiO2 nanoparticle
      in artificial and natural waters.
AB  - Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in a
      variety of products, including textiles. PBDEs are thus exposed to the natural
      environment, including wastewater, waterbodies and sediments (at different phases
      of products' lifecycles), where they will interact with other pollutants. Studies
      on the interactions between organic pollutants and engineered nanoparticles (NPs)
      in natural waters are rare. In this study, we investigated the effects of two
      common PBDEs-BDE 47 and BDE 209-on the physicochemical properties and colloidal
      stability of TiO2 NP in simple aqueous media and two natural waters (river water
      and wastewater). Upon the addition of BDE 47 and BDE 209, the zeta (zeta)
      potential of TiO2 NP increased in magnitude in artificial waters and in natural
      waters (river water and wastewater), but the magnitude of influence on the NP's
      surface charge was specific to each natural water considered. Despite the
      presence of high content of natural organic matter in river water (DOC = 15.8
      mg/L) and wastewater (DOC = 26.1 mg/L), low levels of the PBDEs (e.g. 0.5 mg/L)
      strongly impacted the surface charge and hydrodynamic diameter of TiO2 NP. Both
      PBDE congeners suppressed the agglomeration of TiO2 NP in the presence of
      monovalent and divalent cations, and in both natural waters. BDE 47 exhibited a
      stronger influence than BDE 209 on the surface charge, hydrodynamic diameter, and
      agglomeration of TiO2 NP in both artificial and natural waters. As such, the
      interactions between TiO2 NP and the PBDEs can increase the exposure of aquatic
      organisms to both pollutants. Infrared spectroscopy showed the importance of the
      aromatic ether groups in the adsorption of PBDEs to TiO2 NP.

PMID- 30236470
TI  - Immune Checkpoint Molecules, Personalized Immunotherapy, and Autoimmune Diabetes.
AB  - Although significant progress has been made in understanding autoimmunity, no
      immunotherapy to effectively halt immune-mediated destruction of beta cells in
      type 1 diabetes (T1D) is currently available. For successful immunotherapy it
      will be necessary to identify novel drug targets as well as robust immunologic
      biomarkers to predict disease heterogeneity and patient responsiveness.
      Inhibition of immune checkpoint mechanisms represents a novel and effective
      strategy in tumor immunotherapy. Because they are fundamental to rewiring immune
      circuits, the underlying mechanisms could be therapeutically enhanced and used as
      biomarkers in T1D. We examine here current knowledge of immune checkpoint
      molecules in T1D. One specific immune checkpoint mechanism, namely tryptophan
      metabolism, may meet the need for a valid drug target and robust biomarker in the
      quest for effective and personalized immunotherapy in T1D.

PMID- 30236471
TI  - Additional structured physical activity does not improve walking in older people
      (>60years) undergoing inpatient rehabilitation: a randomised trial.
AB  - QUESTIONS: Among older people receiving inpatient rehabilitation, does additional
      supervised physical activity lead to faster self-selected gait speed at
      discharge? Does additional supervised physical activity lead to better mobility,
      function and quality of life at discharge and 6 months following discharge?
      DESIGN: Multi-centre, parallel-group, randomised controlled trial with concealed
      allocation, assessor blinding, and intention-to-treat analysis. PARTICIPANTS:
      Older people (age>60years) from two Australian hospitals undergoing
      rehabilitation to improve mobility. INTERVENTION: Participants received
      multidisciplinary care, including physiotherapy. During hospital rehabilitation,
      the experimental group (n=99) spent additional time daily performing physical
      activities that emphasised upright mobility tasks; the control group (n=99) spent
      equal time participating in social activities. OUTCOME MEASURES: Self-selected
      gait speed was the primary outcome at discharge and a secondary outcome at the 6
      month follow-up. Timed Up and Go, De Morton Mobility Index, Functional
      Independence Measure and quality of life were secondary outcomes at discharge and
      tertiary outcomes at the 6-month follow-up. RESULTS: The experimental group
      received a median of 20 additional minutes per day (IQR 15.0 to 22.5) of upright
      activities for a median of 16.5days (IQR 10.0 to 25.0). Gait speed did not differ
      between groups at discharge. Mean gait speed was 0.51m/s (SD 0.29) in the
      experimental group and 0.56m/s (SD 0.28) in the control group (effect size 
      0.06m/s, 95% CI -0.12 to 0.01, p=0.096). No significant differences were detected
      in other secondary measures. CONCLUSION: While substantial gains in mobility were
      achieved by older people receiving inpatient rehabilitation, additional physical
      activity sessions did not lead to better walking outcomes at discharge or 6
      months. TRIAL REGISTRATION: ACTRN12613000884707. [Said CM, Morris ME, McGinley
      JL, Szoeke C, Workman B, Liew D, Hill KD, Woodward M, Wittwer JE, Churilov L,
      Danoudis M, Bernhardt J (2018) Additional structured physical activity does not
      improve walking in older people (> 60 years) undergoing inpatient rehabilitation:
      a randomised trial. Journal of Physiotherapy 64: 237-244].

PMID- 30236472
TI  - Training and teaching in anaesthesia and critical care: Towards excellence.

PMID- 30236473
TI  - Ventilation, airway management, complications, perioperative anxiety: Children
      will definitely never be small adults.

PMID- 30236474
TI  - Obstetric anaesthesia: Dynamic and multidirectional research approaches to
      ultimately improve parturient management.

PMID- 30236475
TI  - Reducing patient harm after ambulatory surgery: Lessons from malpractice claims.

PMID- 30236476
TI  - A Contrast in Pathogenic Responses between C57BL/6J and BALB/cJ Mice Using a
      Model of Retinal Injury.
AB  - Ischemia is associated with the pathogenesis of retinal disease, including
      diabetic retinopathy and glaucoma. As a result, the retinal ischemia/reperfusion
      injury model has been used to study neurovascular changes. Historically, murine
      models of retinal disease are established in C57BL/6J (B6) mice, which have been
      described as type 1-dominant responders. In bacterial keratitis models, B6 mice
      are susceptible, whereas BALB/cJ (BALB/c; type 2-dominant) mice exhibit a
      resistant phenotype. As such, we questioned whether the type 1/type 2 paradigm
      could be extrapolated to events associated with retinal pathogenesis. The current
      study compares the retinal response of B6 with BALB/c mice to investigate strain
      specific differences. Retinas were collected at 2 and 10 days after
      ischemia/reperfusion injury to examine differences in neurovascular degeneration,
      leukostasis, oxidative stress, glial activation, and select inflammatory
      mediators. Although both strains showed signs of retinal injury, significantly
      more damage was observed in B6 mice. Retinal thickness was reduced and vascular
      damage was more severe in B6 mice. Exacerbated response to injury in B6 versus
      BALB/c retinas was further supported by increased leukostasis, inflammatory
      mediators, reactive oxygen species, and lipid peroxidation. In addition, more
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive
      cells and increased glial activation were detected in B6 mice. These data
      indicate that B6 and BALB/c retinas differentially respond to injury, which has
      broader implications regarding the development and study of retinal diseases.

PMID- 30236477
TI  - Gain of affinity for VEGF165 binding within the VEGFR2/NRP1 cellular complex
      detected by an HTRF-based binding assay.
AB  - Neuroplin 1 (NRP1), a transmembrane protein interacting with Vascular Endothelial
      Growth Factor VEGF-A165 (called here VEGF165) and the tyrosine kinase Receptor 2
      (VEGFR2) promote angiogenesis and vascular homeostasis. In a pathophysiological
      context, several studies suggested that VEGFR2 and NRP1 mediate tumor development
      and progression. Given the involvement of the VEGF165 network in promoting tumor
      angiogenesis, NRP1, VEGFR2 and VEGF165 have been identified as targets for anti
      angiogenic therapy. No binding assay exists to monitor specifically the binding
      of VEGF165 to the VEGFR2/NRP1 complex in intact cells. We established a binding
      assay based on the homogenous time-resolved fluorescence (HTRF(r)) technology.
      This unique binding assay enables to assess the interaction of VEGF165 with
      VEGFR2 or NRP1 within the VEGFR2/NRP1 complex. Ligand binding saturation
      experiments revealed that VEGF165 binds the VEGFR2/NRP1 complex at the cell
      surface with a ten to twenty-fold higher affinity compared to SNAP-VEGFR2 or SNAP
      NRP1 receptors alone not engaged in the heteromeric complex. The assay allows
      characterizing the impact of NRP1 ligands on VEGF165 to the complex. It shows
      high specificity, reproducibility and robustness, making it compatible with high
      throughput screening (HTS) applications for identifying new VEGF165 antagonists
      selective for NRP1 or the VEGFR2/NRP1 complex.

PMID- 30236478
TI  - [Adjuvant chemotherapy for upper tract urothelial cancer: Level of evidence IA].

PMID- 30236479
TI  - [CAR T cells: Current indications in children and perspectives].
AB  - Acute lymphoblastic leukemia (ALL) is the first cause of cancer in children. Five
      year overall survival is greater than 90% but leukemia remains a major cause of
      death from cancer in children. A new class of immunotherapy based on a chimeric
      antigen receptor "CAR" targeting the CD19 on the B leukemic cells and that is
      transduced in an autologous or allogenic T lymphocyte will allow to transform the
      prognosis of refractory or relapsed B-ALL. Overall response rates range from 60
      to 90% in phase I-II studies in patients with second relapse or more or with
      refractory disease. Persistent remissions and even cures have been observed.
      These very good results could lead to use this treatment in first line for
      patients with very high-risk disease. However, CAR T cells production, costs and
      adverse events management represent major issues for the future of this
      therapeutic. The occurrence of CD19 negative relapses has led to develop
      bispecific CAR T cells. Allogeneic CAR would permit to obtain a "CAR garage" off
      the shelf available from the diagnosis. Perspectives for CAR T cells are immense
      but will involve technological progresses around the CAR conception and
      production, leading to further improved results in leukemias (ALL but also AML)
      and lymphomas and hopefully the emergence of efficacy in childhood solid tumors.

PMID- 30236480
TI  - Carbon monoxide ameliorates Staphylococcus aureus-elicited COX-2/IL-6/MMP-9
      dependent human aortic endothelial cell migration and inflammatory responses.
AB  - Staphylococcus aureus (S. aureus) can often lead to many life-threatening
      diseases. It has the ability to invade normal endovascular tissue. Acute
      inflammation and its resolution are important to ensure bacterial clearance and
      limit tissue injury. Carbon monoxide (CO) has been shown to exert anti
      inflammatory effects in various tissues and organ systems. In our study, we
      investigated the effects and the mechanisms of carbon monoxide releasing molecule
      2 (CORM-2) on S. aureus-induced inflammatory responses in human aortic
      endothelial cells (HAECs). We proved that S. aureus induced cyclooxygenase-2 (COX
      2)/prostaglandin E2 (PGE2)/interleukin-6 (IL-6)/matrix metallopeptidase-9 (MMP-9)
      expression and cell migration, which were decreased by CORM-2. Moreover, CORM-2
      had no effects on TLR2 mRNA levels in response to S. aureus. Interestingly, we
      proved that S. aureus decreased intracellular ROS generation, suggesting that the
      inhibition of ROS further promoted inflammatory responses. However, CORM-2
      significantly inhibited S. aureus-induced inflammation by increasing
      intracellular ROS generation. S. aureus-induced NF-kappaB activation was also
      inhibited by CORM-2. Finally, we proved that S. aureus induced levels of the
      biomarkers of inflammation in cardiovascular diseases, which were inhibited by
      CORM-2. Taken together, these results suggest that CORM-2 inhibits S. aureus
      induced COX-2/PGE2/IL-6/MMP-9 expression and aorta inflammatory responses by
      increasing the ROS generation and reducing the inflammatory molecules levels.

PMID- 30236481
TI  - Increased levels of soluble co-stimulatory molecule PD-L1 (B7-H1) in the plasma
      of viraemic HIV-1+ individuals.
AB  - Recent evidence has revealed that PD-L1 is expressed in two functional forms,
      namely, a membrane-bound form (mPD-L1) and a soluble form (sPD-L1). The
      identification of the soluble form of PD-L1 represents the discovery of a new
      potential mechanism for the activation of the PD-1 pathway that may mediate a
      physiological apoptotic mechanism through a cell-cell signalling-independent
      pathway and may also favour T cell dysfunction during HIV infection. Since the
      presence of sPD-L1 has not been well established in the scenario of chronic viral
      infection, we investigated the presence of sPD-L1 in the plasma of viraemic HIV+
      individuals and the potential mechanism that promotes its production. We report
      the following: 1) the level of the soluble form of PD-L1 is increased in the
      plasma of viraemic HIV+ individuals, 2) the level of the soluble form of PD-L1 in
      viraemic HIV+ individuals correlates with markers of microbial product
      translocation and inflammation, 3) the expression of the membrane-bound form of
      PD-L1 on conventional dendritic cells from viraemic HIV+ individuals correlates
      with the levels of soluble PD-L1 and MMP-2, and 4) monocyte-derived dendritic
      cells not only increase their expression of mPD-L1 and MMP-2 but also produce sPD
      L1 after LPS and TNF-alpha stimulation, as demonstrated by functional in vitro
      experiments, which provides insight into the potential source of sPD-L1
      production.

PMID- 30236482
TI  - Vitamin D levels are associated with metabolic syndrome in adolescents and young
      adults: The BCAMS study.
AB  - BACKGROUND AND AIMS: The relationship between vitamin D deficiency and metabolic
      syndrome (MS) remains controversial with relatively sparse data among youth.
      Therefore, we attempted to explicate the association of 25-hydroxyvitamin D
      [25(OH)D] levels with MS in Chinese adolescents and young adults. METHODS: A
      cohort of 559 subjects at elevated risk of MS were recruited at 14-28 years of
      age as a follow-up to the Beijing Child and Adolescent Metabolic Syndrome Study.
      Subjects underwent clinical assessment including a 2h-oral glucose tolerance
      test. The concentrations of 25(OH)D, glucose, insulin and lipids were determined.
      MS was defined using the 2009 harmonized definition. RESULTS: The prevalence of
      vitamin D deficiency (< 20 ng/ml) was 78.3%. After adjusting for age, gender and
      season, 25(OH)D concentrations were negatively correlated with neck
      circumference, percent body fat, LDL cholesterol, fasting and 2h-glucose levels
      (all P < 0.05). 25(OH)D levels were significantly lower in participants with
      obesity, high triglycerides, type 2 diabetes, or MS, compared to their respective
      counterparts (all P < 0.05). After adjusting for potential confounders (e.g.,
      body mass index), participants in the lowest 25(OH)D tertile were 2.5 times more
      likely to exhibit MS than were those in the highest tertile (Odds Ratio: 2.48;
      95% CI: 1.13-5.45, P < 0.05). CONCLUSIONS: Vitamin D deficiency was very common
      in this young Chinese population at risk for MS. Given this association between
      low vitamin D levels and MS, the role of vitamin D supplementation in Chinese
      youths needs further examination, particular in those at risk for MS.

PMID- 30236483
TI  - Staggered Target SELEX, a novel approach to isolate non-cross-reactive aptamer
      for detection of SEA by apta-qPCR.
AB  - BACKGROUND AND OBJECTIVE: Aptamers or chemical antibodies are oligonucleotides
      (DNA or RNA) that are able to bind to various targets with high specificity and
      affinity such as toxins which are isolated by an in vitro method known as SELEX.
      To date, there are many SELEX procedures for the isolation of novel aptamers
      against proteins. However not all modified SELEX are suitable for similar protein
      based on sequence homology such as staphylococcal enterotoxins. Staphylococcal
      enterotoxin type A (SEA) is the most prevalent toxin involved in staphylococcal
      food poisoning (SFP) worldwide. SEA is homologous to Staphylococcal enterotoxin
      type D (SED) and Staphylococcal enterotoxin type E (SEE) about 50% and 83%,
      respectively. Here, we have developed Staggered Target SELEX (ST-SELEX) as a
      novel designed SELEX procedure to acquire specific non-cross-reactive aptamers
      against SEA as a model protein. METHODS: In this study, isolated ssDNA aptamers
      by ST-SELEX were used for detection of SEA via apta-Real time PCR (apta-qPCR).
      After in silico analysis of SEA protein with SEE and finding the specific region
      on the surface of protein, ST-SELEX was carried out in two steps (classical SELEX
      and Second SELEX). Finally, after isolating high specific aptamers, the apta-qPCR
      was used for the detection of the SEA. In this technique, poly-clonal antibody
      against SEA was immobilized on protein G sepharose beads (Ab-PGs). Then, the SEA
      protein was captured by poly clonal antibody as the target that immobilized on
      sepharose beads. The isolated aptamers were bound on the surface of SEA protein
      that captured by Ab-PGs. Finally, the heat-released aptamers were amplified by
      qPCR. RESULT: Our investigation showed that the aptamers were generated in vitro
      by a ten-round selection process based on ST-SELEX procedure with dissociation
      constant (KD) value 7.44+/- 0.6 nM and limit of detection (LOD) of 146.67 fM.
      DISCUSSION AND CONCLUSION: The advantage of ST-SELEX compared to other SELEX
      methods was to select a specific non cross-reactive aptamer against two or more
      proteins with high sequence homology. These aptamers can be used in sensitive
      detection methods such as apta-qPCR.

PMID- 30236484
TI  - A review of NICE appraisals of pharmaceuticals 2000-2016 found variation in
      establishing comparative clinical effectiveness.
AB  - OBJECTIVE: To identify and assess the methods for estimating comparative clinical
      effectiveness for novel pharmaceutical products licensed on the basis of
      nonrandomized controlled trial (non-RCT) data and to evaluate the corresponding
      National Institute for Health and Care Excellence (NICE) recommendations.
      METHODS: Our identification strategy was twofold. First, we reviewed all NICE
      appraisals between 2010 and 2016 and identified technologies where comparative
      clinical effectiveness estimates were calculated using non-RCT data. Second, we
      checked if NICE appraisals completed from 2000 to 2010 had included
      pharmaceuticals that were granted European Medicines Agency marketing
      authorization without RCT data between 1999 and 2014. Information was extracted
      on the method used to establish comparative clinical effectiveness as well as the
      corresponding NICE recommendations. We also collected information on the
      rationale for utilizing non-RCT data in NICE appraisals. RESULTS: Of 489
      individual pharmaceutical technologies assessed by NICE, 22 (4%) used non-RCT
      data to estimate comparative clinical effectiveness. Methods for establishing
      external controls in such studies varied: 13 (59%) used published trials, 6 (27%)
      used observational data, 2 (9%) used expert opinion, and 1 (5%) used a responder
      vs nonresponder analysis. Only 5 (23%) used a regression model to adjust for
      covariates. We did not observe a notable difference in the proportion of
      pharmaceutical technologies that received a positive recommendation from NICE
      whether the decision was based on RCT or non-RCT data (83% vs 86%). CONCLUSIONS:
      To date, a small number of appraisals by NICE based on non-RCT data did not
      result in substantially different treatment decisions. The majority of the
      technologies appraised on the basis of non-RCT data either received a positive
      recommendation or a positive recommendation with restrictions. The methods used
      to calculate comparative clinical effectiveness estimates varied, highlighting
      the need to establish clear guidance.

PMID- 30236485
TI  - Increased ischemic stroke, acute coronary artery disease and mortality in
      patients with granulomatosis with polyangiitis and microscopic polyangiitis.
AB  - OBJECTIVE: The aim of our study was to assess major cardiovascular event
      incidence, predictors, and mortality in ANCA-associated vasculitis (AAV).
      METHODS: We conducted a retrospective cohort study of all GPA or MPA, according
      to Chapel Hill Consensus Conference classification criteria, diagnosed between
      1981 and 2015. Major cardiovascular event was defined as acute coronary artery
      disease, or ischemic stroke, or peripheral vascular disease requiring a
      revascularization procedure. We calculated the comparative morbidity/mortality
      figure (CMF) and we used Cox proportional hazards regression models to assess the
      risk of coronary artery disease, ischemic stroke associated with AAV, after
      adjusting for covariates. RESULTS: 125 patients, 99 GPA (79,2%) and 26 MPA
      (20,8%), were followed 88.4 +/- 78.3 months. Ischemic stroke incidence was four
      times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31).
      Coronary artery disease incidence was four times higher than in the general
      population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary
      artery disease were strongly associated with coronary artery disease occurrence
      (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5,
      respectively). ENT flare-up was an independent protective factor for coronary
      artery disease occurrence. We did not identify factors significantly associated
      with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person
      years. Mortality in AAV was 1.5 times higher than in the general population (CMF
      1.56; 95% CI 1.34-1.83). CONCLUSION: AAV have a significantly increased risk of
      mortality, ischemic stroke, and coronary artery disease.

PMID- 30236486
TI  - Localization of the 1,25-dihydroxyvitamin d-mediated response in the intestines
      of mice.
AB  - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D) elicits a transcriptional response in the
      intestines. Assessments of this response are often derived from crude tissue
      homogenates and eliminate the ability to discriminate among different cell types.
      Here, we used an RNA in situ hybridization assay, RNAScope (Advanced Cell
      Diagnostics, Newark, CA), to identify the cells in the intestine that respond to
      1,25(OH)2D with expression of cytochrome P450 family 24 subfamily A member 1
      (Cyp24a1) mRNA. Mice were gavaged with a single bolus dose of 1,25(OH)2D to
      target the duodenum or a glucuronic acid conjugate of 1,25(OH)2D, beta-G
      1,25(OH)2D, to target the colon. QRT-PCR analysis of Cyp24a1 mRNA verified that
      the 1,25(OH)2D-induced responses were present. RNAScope revealed that the mRNA
      response present after six hours is limited to mature enterocytes exposed to the
      intestinal lumen in both the duodenum and colon. No detectable expression was
      observed in goblet cells, lamina propria, muscularis mucosa muscle, submucosa and
      submucosal lymphoid follicles, or tunica muscularis. Our findings have identified
      epithelial enterocytes to be the intestinal targets for 1,25(OH)2D in both the
      duodenum and colon.

PMID- 30236487
TI  - The regulatory role of Annexin 3 in a nude mouse bearing a subcutaneous xenograft
      of MDA-MB-231 human breast carcinoma.
AB  - The following study investigated the effects of Annexin A3 (ANXA3) on breast
      cancer biological behavior in vivo, using nude mouse model bearing a subcutaneous
      tumor. A total of 18 female nude mice were randomly divided into three groups (n
      = 6): negative control group which was inoculated with MDA-MB-231 cells, blank
      control group which was inoculated with MDA-MB-231-NC cells, and the transfection
      group which was inoculated with MDA-MB-231-Sh cells. The experiment lasted for 4
      weeks, during which mice conditions, diet and defecation were monitored on a
      daily basis. Body weight, as well as tumor diameters, which were assessed using
      standard caliper method, were measured once a week. In vivo imaging was performed
      to detect the activity of transplanted tumors. H&E staining was used to analyze
      the histological structure of tumor tissues in three groups, while flow cytometry
      and fluorescent RT-PCR were performed to measure cell proliferation and the
      expression of ANXA3 mRNA. Briefly, significantly slower tumor growth and tumor
      activity were observed in the transfection group compared to negative and blank
      controls, while the tumor weight and volume in this group were also significantly
      lower compared to the other two groups (P < 0.01). Sparse tumor cells accompanied
      with massive fibrous connective tissue proliferation, and lower new blood vessels
      formation were observed in transfection group compared to other groups. Moreover,
      mRNA and protein levels of ANXA3 were significantly lower in transfection group
      compared to the other two groups (P < 0.01). In addition, lower proliferation
      index and higher G0/1 cell count were observed in transfection group compared to
      negative and blank controls (P < 0.01). To sum up, these results suggested that
      ANXA3 silencing regulates the proliferation and inhibits the growth of MDA-MB-231
      breast cancer cells. Consequently, ANXA3 might be used as a potential target for
      gene therapy in breast cancer.

PMID- 30236488
TI  - Rectal resection following neoadjuvant therapy in a Midwest community hospital
      setting: The case for standardization over centralization as the means to
      optimize rectal cancer outcomes in the United States.
AB  - BACKGROUND: Incomplete and flawed national databases reveal strikingly inferior
      outcomes for rectal cancer patients resected at "low" versus "high " volume
      hospitals, therefore, a study of outcomes of a "high" volume surgeon in a "low"
      volume Midwest community hospital setting examined this perception in comparison
      to contemporary studies. METHODS: Review of 109 consecutive patients who
      underwent open resection of rectal cancer following neoadjuvant therapy, 1999
      2010. RESULTS: Despite the majority of tumors in the low rectum (54%), the rate
      of abdominoperineal resection was only 39% with R0 resection achieved in 94% and
      primary anastomosis in 61/109 patients (56%). Disease-free survival (DFS) 73%:
      stage 0 (complete response)- 100%, stage I- 88%, stage II- 68%, stage III- 50%,
      stage IV- 0% with recurrence rate of 11% (local recurrence (LR) - 3%, distant -
      8%). CONCLUSION: Outcomes of rectal cancer resection by a "high" volume surgeon
      in a "low" volume Midwest community hospital setting were comparable to
      contemporary studies from tertiary care institutions. Geographic location and
      hospital capacity matter less than access to multispecialty expertise providing
      neoadjuvant therapy and following standard principles of oncologic resection, in
      efforts to optimize rectal cancer outcomes.

PMID- 30236490
TI  - Modelling the Human Cortex in Three Dimensions.
AB  - In cognitive neuroscience, brain-behaviour relationships are usually mapped onto
      a 2D cortical sheet. Cortical layers are a critical but often ignored third
      dimension of human cortical function. Improved resolution has put us on the
      threshold of beginning to image human cognition in three dimensions.

PMID- 30236491
TI  - Catheter-Directed Thrombolysis for Portal Vein Thrombosis in Children: A Case
      Series.
AB  - PURPOSE: To describe safety and efficacy of catheter-directed thrombolysis (CDT)
      for portal vein thrombosis (PVT) in children. MATERIALS AND METHODS:
      Retrospective review was performed of 10 consecutive patients (7 girls, 3 boys;
      mean age 11.9 y; range, 3-17 y) with PVT undergoing CDT at a single tertiary
      children's hospital between August 2005 and March 2016. PVT was categorized by
      etiology and extent (intrahepatic, extrahepatic, or both). CDT was performed with
      infusion catheters placed via percutaneous transhepatic (PTH) and/or transjugular
      intrahepatic (TJ) approaches, with or without the use of adjunctive maneuvers,
      including balloon maceration and suction and rheolytic thrombectomy. Degree of
      thrombolysis on portal venography, presence of portal vein thrombus on available
      follow-up imaging, and complication rates were recorded. RESULTS: In 10 patients,
      13 CDT procedures were performed for PVT, with 3 patients requiring repeat CDT.
      Portal access was achieved with PTH (n = 6), TJ (n = 2), or combined (n = 2)
      approaches. All cases were successful in re-establishing patency and hepatopetal
      flow on portal venography with complete thrombolysis achieved in 10 of 13 cases
      (77%). Two major complications (20%) occurred, both with PTH access. Mean follow
      up time for 9 patients was 2.6 years (range, 51-1,902 d) with long-term patency
      achieved in 6 (67%). CONCLUSIONS: CDT can be safe and effective for PVT in
      children. Portal access considerations and early initiation of thrombolysis may
      further increase safety and efficacy.

PMID- 30236492
TI  - Chimera states in neuronal networks: A review.
AB  - Neuronal networks, similar to many other complex systems, self-organize into
      fascinating emergent states that are not only visually compelling, but also vital
      for the proper functioning of the brain. Synchronous spatiotemporal patterns, for
      example, play an important role in neuronal communication and plasticity, and in
      various cognitive processes. Recent research has shown that the coexistence of
      coherent and incoherent states, known as chimera states or simply chimeras, is
      particularly important and characteristic for neuronal systems. Chimeras have
      also been linked to the Parkinson's disease, epileptic seizures, and even to
      schizophrenia. The emergence of this unique collective behavior is due to diverse
      factors that characterize neuronal dynamics and the functioning of the brain in
      general, including neural bumps and unihemispheric slow-wave sleep in some
      aquatic mammals. Since their discovery, chimera states have attracted ample
      attention of researchers that work at the interface of physics and life sciences.
      We here review contemporary research dedicated to chimeras in neuronal networks,
      focusing on the relevance of different synaptic connections, and on the effects
      of different network structures and coupling setups. We also cover the emergence
      of different types of chimera states, we highlight their relevance in other
      related physical and biological systems, and we outline promising research
      directions for the future, including possibilities for experimental verification.

PMID- 30236489
TI  - The Regulatory Role of the Human Mediodorsal Thalamus.
AB  - The function of the human mediodorsal thalamic nucleus (MD) has so far eluded a
      clear definition in terms of specific cognitive processes and tasks. Although it
      was at first proposed to play a role in long-term memory, a set of recent studies
      in animals and humans has revealed a more complex, and broader, role in several
      cognitive functions. The MD seems to play a multifaceted role in higher cognitive
      functions together with the prefrontal cortex and other cortical and subcortical
      brain areas. Specifically, we propose that the MD is involved in the regulation
      of cortical networks especially when the maintenance and temporal extension of
      persistent activity patterns in the frontal lobe areas are required.

PMID- 30236493
TI  - Compound heterozygous RYR1 mutations by whole exome sequencing in a family with
      three repeated affected fetuses with fetal akinesia.

PMID- 30236494
TI  - The Role of Perioperative Statin Use in the Prevention of Delirium After Total
      Knee Replacement Under Spinal Anesthesia.
AB  - BACKGROUND: The relationship between statin use and incidence of postoperative
      delirium (POD) is controversial. We investigated the association between
      perioperative statin use and occurrence of delirium after total knee arthroplasty
      (TKA) under spinal anesthesia. METHODS: We retrospectively reviewed the
      electronic medical records of patients who underwent TKA under spinal anesthesia
      at a single tertiary care hospital between January 2005 and October 2017. POD
      incidence was recorded for patients who received statins continuously from 1
      month before surgery until discharge and for patients who did not receive any
      statins. Univariable and multivariable logistic regression analyses were
      conducted to investigate an association between occurrence of POD and
      perioperative statin use. RESULTS: In total, 6020 procedures were included, and
      992 (16.4%) were associated with perioperative statin use. POD was confirmed for
      304 (5.0%) procedures. The statin group showed a 1.7% significant lower incidence
      (P = .017) of POD (35/992, 3.5%) than the no statin group (1420/5,028, 5.4%). In
      multivariable logistic regression analysis, the POD incidence in the statin group
      was 34% lower than that in the no statin group (odds ratio [OR] 0.66, 95%
      confidence interval [CI] 0.45-0.97, P = .036]. Moreover, the POD incidence was
      decreased by 37% (OR 0.63, 95% CI 0.40-0.99, P = .047) and 79% (OR 0.21, 95% CI
      0.05-0.88, P = .033) respectively, when atorvastatin and simvastatin were
      administered. CONCLUSION: Continuous perioperative statin use may be associated
      with a significantly lower risk of delirium after TKA under spinal anesthesia;
      simvastatin was the most effective statin for POD prevention.

PMID- 30236495
TI  - Two-Stage Revision Total Hip Arthroplasty With a Specific Articulating Antibiotic
      Spacer Design: Reliable Periprosthetic Joint Infection Eradication and Functional
      Improvement.
AB  - BACKGROUND: Two-stage revision utilizing spacers loaded with high-dose antibiotic
      cement prior to reimplantation remains the gold standard for treatment of
      periprosthetic joint infections (PJI) in total hip arthroplasty (THA) in North
      America, but there is a paucity of data on mid-term outcomes. We sought to
      analyze the survivorship free of infection, clinical outcomes, and complications
      of a specific articulating spacer utilized during 2-stage revision. METHODS: One
      hundred thirty-five hips (131 patients) undergoing a 2-stage revision THA for PJI
      with a specific articulating antibiotic spacer design from 2005 to 2013 were
      retrospectively reviewed. Infections were classified according to the
      Musculoskeletal Infection Society criteria. Mean age at resection was 65 years
      and mean follow-up was 5 years (rang, 2-10). RESULTS: Survivorship free of any
      infection after reimplantation was 92% and 88% at 2 and 5 years, respectively.
      Patients with a host-extremity grade of C3 compared to all patients with a host
      grade of A [hazard ratio (HR) 4.1, P = .05] were significant risk factors for
      poorer infection-free survivorship after reimplantation. Harris hip scores
      improved from a mean of 58 to a mean of 71 in the spacer phase (P = .002) and a
      mean of 81 post-reimplantation (P = .001). Fourteen (10%) patients dislocated
      after reimplantation, 9 (7%) of which required re-revision. Trochanteric
      deficiency (HR 19, P < .0001), dislocation of the articulating spacer prior to
      reimplantation [which occurred in 7 (5%) patients, 5 of whom subsequently
      dislocated the definitive implant] (HR 16, P < .0001), and female gender (HR 5, P
      = .002) were significant risk factors for post-reimplantation dislocation.
      CONCLUSION: Insertion of an articulating antibiotic spacer during a 2-stage
      revision THA for PJI demonstrates reliable infection eradication and improvement
      in clinical function, including the spacer phase. Patients with trochanteric
      deficiency and an articulating spacer dislocation are at high risk of post
      reimplantation dislocation; judicial use of a dual-mobility or constrained device
      should be considered in these patients.

PMID- 30236496
TI  - [Evidence of community engagement in health in Spain: thoughts and proposals.
      SESPAS Report 2018].
AB  - Community engagement has recently become key in the development of health
      promotion programmes at a local level. However, evidence-based tools are
      necessary to implement strategies and interventions with a participatory
      approach. The objective of this article is to reflect on the existing evidence in
      Spain about community engagement in health, drawing on the results of the AdaptA
      GPS Project (Adapt and Apply Health Promotion Guidelines), intended to adapt NICE
      guideline NG44 on community engagement to improve health and wellbeing, and to
      reduce inequalities. After describing the methodology for the adaptation process,
      we discuss some of the findings from the review of the evidence on community
      engagement in the Spanish context. We ask whether the limited evidence identified
      is due to the difficulties involved in evaluating these interventions, or to the
      lack of interest in these programmes and the limited resources and funding
      dedicated to them. Two recommendations are proposed: to promote more and better
      research, fostering training, research and evaluation towards the development of
      community engagement interventions in health, and to promote more and better
      interventions using evidence-based tools, supporting their long-term
      sustainability by taking into account the time needed for community engagement
      programmes to be properly developed. Generating more evidence on community
      engagement in health in Spain will allow us to learn from successful processes
      and encourage the transfer of good practice to different contexts.

PMID- 30236497
TI  - Controversial results of the Revised Cardiac Risk Index in elective open repair
      of abdominal aortic aneurysms: Retrospective analysis on a continuous series of
      899 cases.
AB  - BACKGROUND: Low reliability of Revised Cardiac Risk Index (RCRI) in predicting
      major cardiac events (MACE) among Vascular Surgery patients emerged in recent
      literature, suggesting procedure-specific risk evaluation - particularly in major
      surgery. METHODS-RESULTS: Comorbidities, perioperative variables, RCRI and MACE
      were retrospectively analyzed in a consecutive series of 899 elective open
      abdominal aortic aneurysm (AAA) repairs performed at our Institution. Possible
      MACE predictors were studied through univariate/multivariable analysis (logistic
      regression, MVRE) and stepwise-backward elimination/odds ratio (MVR-SBE/OR).
      Patients were divided by clampsite in 2 subgroups: 1. infrarenal (690 cases); 2.
      pararenal (209 cases). RCRI resulted predictive for MACE in the whole dataset but
      its performance resulted lower for pararenal aneurysms (p = 0.11) than for
      infrarenal ones (p <= 0.00). Among RCRI covariates of the whole cohort, dilated
      cardiomyopathy (p <= 0.001), ischemic cardiopathy (p <= 0.01) and cerebrovascular
      disease (p <= 0.02) resulted predictive. Peripheral arteriopathy also related to
      MACE (p <= 0.03). At MVR-SBE/OR analysis, the following resulted to be MACE
      predictors: dilated cardiomyopathy (p <= 0.001), cerebrovascular disease (p <=
      0.02), and surgical access (p = 0.04) in subgroup 1; previous myocardial
      infarction (p <= 0.01), congestive failure (p <= 0.03) and chronic pneumopathy (p
      = 0.04) in subgroup 2. CONCLUSIONS: Predictability of RCRI in elective AAA
      surgery is influenced by clampsite and resulted to be lower in aneurysms
      requiring suprarenal clamping. Variables included in the RCRI show to have
      different weights when patients are stratified by clampsite. Some variables not
      included in the RCRI model significantly affect the onset of MACE. RCRI should be
      revised to elaborate a specific score for AAAs including further MACE predictors,
      to improve risk assessment and to support proper surgical strategy.

PMID- 30236498
TI  - Oxidative stress and cardiovascular risk prediction: The long way towards a
      "radical" perspective.

PMID- 30236499
TI  - Psoriatic disease, aging, chronic inflammation and acute coronary syndromes. Two
      and two may not always make four.

PMID- 30236500
TI  - Benefits of final proximal optimization technique (POT) in provisional stenting.
AB  - AIMS: Initial proximal optimization technique (POT) in provisional stenting
      improves global malapposition, side-branch (SB) obstruction (SBO) and
      conservation of arterial circularity. The specific mechanical effects of a final
      POT sequence concluding the main provisional stenting techniques, on the other
      hand, are unknown. METHODS AND RESULTS: SynergyTM stents were implanted on
      fractal coronary bifurcation bench models using the main provisional stenting
      techniques (n = 5 per group): kissing-balloon inflation (KBI), snuggle, and rePOT
      (initial POT + SB inflation + final POT). Final results were quantified on 2D and
      3D OCT before and after final POT. Whichever the technique, final POT
      significantly decreased global malapposition (from 7.6 +/- 5.3% to 2.2 +/- 2.5%,
      p < 0.05) and proximal elliptic deformation (from 1.15 +/- 0.07 to 1.09 +/- 0.04,
      p < 0.05), without impact on SBO (from 11.5 +/- 9.6% to 12.9 +/- 10.6%, NS).
      However, final POT failed to completely correct the elliptic deformation induced
      by balloon juxtaposition during the KBI and snuggle techniques, with final
      elliptic ratios of 1.11 +/- 0.03 and 1.11 +/- 0.04 respectively, significantly
      higher than with the complete rePOT sequence: 1.05 +/- 0.02 (p < 0.05).
      CONCLUSIONS: Like initial POT, final POT is recommended whatever the provisional
      stenting technique used. However, final POT fails to completely correct all
      proximal elliptic deformation associated with "kissing-like" techniques, in
      contrast to results with the rePOT sequence.

PMID- 30236501
TI  - What is left to prevent contrast-induced acute kidney injury? No difference
      between low and iso-osmolar contrast media.

PMID- 30236502
TI  - Safety and efficacy of Tirofiban in STEMI-patients.
AB  - BACKGROUND: Tirofiban is recommended as bail out therapy in patients with ST
      elevation myocardial infarction (STEMI). However, evidence regarding safety and
      efficacy of tirofiban is unclear. Tirofiban has been shown to improve ST
      resolution, to decrease infarct size (IS) and to reduce incidence of major
      adverse cardiac and cerebrovascular events (MACCE). However, bleeding is enhanced
      in tirofiban treated patients. In this study, we aim to investigate efficacy and
      safety of Tirofiban in STEMI-patients. METHODS: 610 STEMI patients were analyzed.
      MACCE (death, myocardial infarction [MI], stroke) and TIMI bleeding events were
      registered during hospital course and 12 month follow-up. RESULTS: Tirofiban
      patients were slightly younger (tirofiban 63 +/- 13 years vs. control 65 +/- 14
      years; p = 0.04). They had higher peak-high-sensitive troponin T [Hs-TnT]
      (tirofiban 6561 +/- 11,065 vs. control 4594 +/- 11,200, p-value = 0.047) and peak
      creatine kinase [CK] (tirofiban 2742 +/- 5097 vs. control 1416 +/- 2160, p-value
      < 0.0001). Percutaneous coronary intervention (PCI) was more complex in tirofiban
      treated patients as radiation time (tirofiban 18 +/- 15 vs. control 14 +/- 13; p
      value = 0.02) and use of contrast agent (tirofiban 240 +/- 106 vs. control 209 +/
      99; p-value = 0.01) was higher in tirofiban patients. However, there were no
      differences in MACCE (HR 0.877, 95% CI 0.62-1.25, p = 0.47) and bleeding (major:
      HR 1.494, 95% CI 0.65-3.44, p = 0.34; minor: HR 1.294, 95% CI 0.67-2.52, p =
      0.45). CONCLUSION: MACCE and bleeding events were similar. However, PCI was more
      complex and infarcts larger in tirofiban treated patients.

PMID- 30236503
TI  - Cardiac electrical and mechanical alterations - united in the long QT syndrome.

PMID- 30236505
TI  - Brain structural and functional alterations in insomnia disorder: More
      "homogeneous" research is needed.

PMID- 30236504
TI  - Myocarditis and pericarditis after immunization: Gaining insights through the
      Vaccine Adverse Event Reporting System.

PMID- 30236506
TI  - Use of electronic portal images to evaluate setup error and intra-fraction motion
      during free-breathing breast IMRT treatment.
AB  - Before delivering of intensity-modulated radiotherapy, kilo-voltage image
      guidance radiotherapy is widely used in setup error correction and monitoring
      intra-fraction motion effectively. Accordingly, this study proposes and tests an
      image integration technique for observing intra-fraction motion during beam
      delivery, with the wider objective of reducing both image-guidance time and the
      dose delivered to normal breast tissue. The study sample comprised 33 female
      patients with breast cancer, and 241 sets of portal images acquired using a
      VARIAN aSi-1000 electronic portal imaging device. Motion amplitudes and vectors
      were collected and calculated separately by two senior therapists. The setup
      error in 3 axes was computed for every fraction, with average shifting for
      lateral, longitudinal and vertical direction was -0.3-mm +/- 0.5, -0.1-mm +/- 0.5
      and -0.6-mm +/- 1.6, with the average vector of setup error being 2.9-mm +/- 1.4.
      The average intra-fraction motion for vertical direction was (A: -0.1-mm +/- 1.0;
      B: -0.0 +/- 1.1), for longitudinal was (A: -0.4-mm +/- 1.7; B: 2.0 +/- 1.1), and
      for lateral direction was (A: 0.3-mm +/- 1.3; B: 0.2 +/- 1.8). The average intra
      fraction vector was 2.9-mm +/- 1.3 for therapist A, and 3.4-mm +/- 1.8 for
      therapist B. Offline Review commercial software was utilized for setup error and
      motion analysis, and data analysis and reliability testing were conducted with
      statistical package of the social sciences. Pearson correlations between the two
      therapists was moderate (0.59, p << 0.01), and the Cohen's kappa value for inter
      rater agreement between different evaluators was fair in the anterior-posterior
      direction (0.25, p << 0.01), with slight agreement in other two directions and
      vectors. The study presented efficient and dose reduction method to evaluate
      setup error and intra-fraction motion during breast intensity-modulated
      radiotherapy treatment.

PMID- 30236508
TI  - Generation of a synthetic binary plasmid that confers resistance to
      nourseothricin for genetic engineering of Sporothrix schenckii.
AB  - Some members of the Sporothrix genus can cause sporotrichosis, a worldwide
      distributed mycosis that affects several mammalian species, including human
      beings. Sporothrix schenckii and Sporothrix brasiliensis are the fungal species
      frequently associated with this disease, and the latter has gained significant
      interest because of the increased number of cases associated with transmission by
      cats. Despite the relevance of these organisms in the medical field, limited
      strategies for their genetic manipulation have been explored. Thus far, gene
      silencing using the hygromycin B resistance cassette is the sole strategy
      currently available to study these organisms. Here, we report the generation of a
      cassette that confers resistance to nourseothricin, which was successfully
      transferred from Agrobacterium tumefaciens to Sporothrix cells. Therefore, this
      can be used as a second selective marker to manipulate the genome of these
      organisms.

PMID- 30236507
TI  - Efficacy of S-1 monotherapy for older patients with unresectable pancreatic
      cancer: A retrospective cohort study.
AB  - OBJECTIVES: Pancreatic cancer is a fatal malignancy that frequently occurs in
      older patients. However, limited evidence is available on the effects of
      chemotherapy on older patients with unresectable pancreatic cancer. Here we
      explored the efficacy of S-1, an oral fluorouracil drug, compared with
      gemcitabine, as first-line chemotherapy. MATERIALS AND METHODS: We conducted a
      retrospective cohort study of patients with unresectable pancreatic cancer aged
      >=75 years. For this purpose, we used the claims and master databases of the
      Fukuoka Prefecture Wide-Area Association of Latter-Stage Elderly Healthcare
      between April 1, 2010 to March 31, 2017. According to first-line chemotherapy, we
      divided patients into gemcitabine and S-1 groups to compare three-year survival
      from the date of diagnosis and time to second-line chemotherapy as a surrogate
      indicator of progression-free survival. We analyzed the data using multivariate
      Cox proportional hazards method. RESULTS: The study comprised 680 patients, of
      which 92.5% (N = 629) died within three years of diagnosis. The S-1 group had a
      significantly lower risk of death within three years of diagnosis (hazard ratio
      (HR) 0.695, 95% CI: 0. 588-0. 821, p < .001). There were no significant
      differences (HR 0.968, 95% CI: 0.708-1.324, p = .838) in time to second-line
      chemotherapy. Two sensitivity analyses excluding study subjects who received
      radiation therapy or second-line chemotherapy yielded consistent results (HR
      0.746, 95% CI: 0.622-0.895, p = .002, HR 0.628, 95% CI: 0. 509-0.776, p < .001,
      respectively). CONCLUSION: S-1 can serve as a first-line chemotherapeutic option
      of patients aged >=75 years with unresectable pancreatic cancer.

PMID- 30236510
TI  - Utilization of Prostate Cancer Quality Metrics for Research and Quality
      Improvement: A Structured Review.
AB  - BACKGROUND: The shift toward value-based care in the United States emphasizes the
      role of quality measures in payment models. Many diseases, such as prostate
      cancer, have a proliferation of quality measures, resulting in resource burden
      and physician burnout. This study aimed to identify and summarize proposed
      prostate cancer quality measures and describe their frequency and use in peer
      reviewed literature. METHODS: The PubMed database was used to identify quality
      measures relevant to prostate cancer care, and included articles in English
      through April 2018. A gray literature search for other documents was also
      conducted. After the selection process of the pertinent articles, measure
      characteristics were abstracted, and uses were summarized for the 10 most
      frequently utilized measures in the literature. RESULTS: A total of 26 articles
      were identified for review. Of the 71 proposed prostate cancer quality measures,
      only 47 were used, and less than 10% of these were endorsed by the National
      Quality Forum. Process measures were most frequently reported (84.5%). Only 6
      outcome measures (8.5%) were proposed-none of which were among the most
      frequently utilized. CONCLUSION: Although a high number of proposed prostate
      cancer quality measures are reported in the literature, few were assessed, and
      the majority of these were non-endorsed process measures. Process measures were
      most commonly assessed; outcome measures were rarely evaluated. In a step to
      close the quality chasm, a "top 5" core set of quality measures for prostate
      cancer care, including structure, process, and outcomes measures, is suggested.
      Future studies should consider this comprehensive set of quality measures.

PMID- 30236509
TI  - Importance of body condition score and ovarian activity on determining the
      fertility in beef cows supplemented with long-acting progesterone after timed-AI.
AB  - The working hypothesis was that supplementation with progesterone (iP4) at early
      diestrus increases pregnancy rates of suckled beef cows with poor body condition
      score (BCS) and/or in anestrus when cows are submitted to timed insemination
      (TAI). The time of ovulation among suckled multiparous (n = 1270) and primiparous
      (n = 303) Nelore cows was synchronized using an estradiol/P4-based protocol for
      TAI (D0). At Day -10, visual evaluation of BCS was performed (scale = 1-5) and
      animals were classified according to an ovarian activity (OA) score: (OA1)
      absence of CL and presence of follicles >= 8 mm, (OA2) absence of CL and presence
      of follicles < 8 mm and (OA3) presence of corpus luteum (CL). On Day 4, animals
      were assigned randomly to receive 150 mg of injectable, long-acting P4 (iP4, n =
      786) or non-iP4 (n = 787). Further, ultrasonic evaluations were performed on D0
      and D4 for measurements of the largest follicle diameter (DF) and CL area,
      respectively. The BCS affected positively DF, CL area and OA. Supplementation
      with iP4 did not affect (P =  0.49) pregnancy rates and there was no significant
      interaction (P > 0.1) of P4 treatment with BCS or OA was detected for conception
      and pregnancy rates. Regardless of iP4, pregnancy rates of cows with moderate
      (2.75-3.25) (59.1%) and high (>= 3.5) (57.8%) BCS were greater than those of cows
      with low (2.0-2.5) BCS (41.5%). Cows in OA2 had a greater P/AI (51.3%) than cows
      in OA1 (41.7%) or OA3 (41.9%). In conclusion, P4 supplementation after TAI did
      not improve P/AI and did not enhance the response to treatment of cows with a low
      BCS, regardless of OA.

PMID- 30236512
TI  - The first prospective trial for von Hippel-Lindau disease: pazopanib.

PMID- 30236511
TI  - Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single
      centre, phase 2 trial.
AB  - BACKGROUND: No approved systemic therapy exists for von Hippel-Lindau disease, an
      autosomal dominant disorder with pleiotropic organ manifestations that include
      clear cell renal cell carcinomas; retinal, cerebellar, and spinal
      haemangioblastomas; pheochromocytomas; pancreatic serous cystadenomas; and
      pancreatic neuroendocrine tumours. We aimed to assess the activity and safety of
      pazopanib in patients with von Hippel-Lindau disease. METHODS: In this non
      randomised, single-centre, open-label, phase 2 trial, adult patients with
      clinical manifestations of von Hippel-Lindau disease were recruited from the
      University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated
      with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue
      treatment if desired by the patient and treating physician. Primary endpoints
      were the proportion of patients who achieved an objective response and safety in
      the per-protocol population. The objective response was measured for each patient
      and each lesion type. Radiographic assessments were done at baseline and every 12
      weeks throughout the study. Activity and safety were assessed with continuous
      monitoring and a Bayesian design. This study is registered with
      ClinicalTrials.gov, number NCT01436227, and is closed to accrual. FINDINGS:
      Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically
      confirmed or clinical features consistent with von Hippel-Lindau disease, of whom
      31 eligible patients were treated with pazopanib. The proportion of patients who
      achieved an objective response was 42% (13 of 31 patients). By lesion sites
      responses were observed in 31 (52%) of 59 renal cell carcinomas, nine (53%) of 17
      pancreatic lesions, and two (4%) of 49 CNS haemangioblastomas. Seven (23%) of 31
      patients chose to stay on the treatment after 24 weeks. Four (13%) of 31 patients
      withdrew from the study because of grade 3 or 4 transaminitis, and three (10%)
      discontinued study treatment because of treatment intolerance with multiple
      intercurrent grade 1-2 toxicities. Treatment-related serious adverse events
      included one case each of appendicitis and gastritis and one patient had a fatal
      CNS bleed. INTERPRETATION: Pazopanib was associated with encouraging preliminary
      activity in von Hippel-Lindau disease, with a side-effect profile consistent with
      that seen in previous trials. Pazopanib could be considered as a treatment choice
      for patients with von Hippel-Lindau disease and growing lesions, or to reduce the
      size of unresectable lesions in these patients. The safety and activity of
      pazopanib in this setting warrants further investigation. FUNDING: Novartis Inc
      and NIH National Cancer Institute core grant.

PMID- 30236513
TI  - Loss of thioredoxin 2 alters mitochondrial respiratory function and induces
      cardiomyocyte hypertrophy.
AB  - Thioredoxin 2 (Trx2), as a member of the thioredoxin system in mitochondria, is
      involved in controlling mitochondrial redox state. However, the role of Trx2 in
      cardiac biology is not fully understood. In the present study, the expression of
      Trx2 is silenced in quiescent neonatal rat ventricular cardiomyocytes (NRVCs) and
      mitochondrial respiratory function and cardiomyocyte hypertrophy are assessed.
      The results show that Trx2 depletion does not induce significant cytotoxicity in
      quiescent NRVCs. Remarkably, Trx2 depletion results in cardiomyocyte hypertrophy
      as determined by increased cell size and protein synthesis. Furthermore, Trx2
      depletion inhibits AMPK activity and AMPK activator reversed cellular
      hypertrophy. Trx2 depletion enhances mitochondrial ROS generation without impact
      on cellular ROS level. Trx2 depletion has no effect on mitochondrial biogenesis.
      Specifically, Trx2 depletion increases mitochondrial respiration flux and total
      ATP concentration under quiescent conditions. To decipher the relationship
      between ROS generation, mitochondrial respiration flux, and AMPK signaling,
      mitochondrial metabolism and ROS was specifically inhibited, and the results show
      that AMPK inactivation and hypertrophic response in Trx2-silenced cells is
      reversed by respiration blockers but not ROS scavenger. In conclusion, these
      results show that beyond mitochondrial ROS scavenging, Trx2 controls
      mitochondrial respiratory function in quiescent cardiomyocytes and is implicated
      in cardiomyocyte hypertrophy via AMPK signaling.

PMID- 30236514
TI  - Acquired disorders with hypopigmentation: A clinical approach to diagnosis and
      treatment.
AB  - Acquired hypopigmented skin changes are commonly encountered by dermatologists.
      Although hypopigmentation is often asymptomatic and benign, occasional serious
      and disabling conditions present with cutaneous hypopigmentation. A thorough
      history and physical examination, centered on disease distribution and
      morphological findings, can aid in delineating the causes of acquired
      hypopigmented disorders. Part II of this two-part series focuses on conditions
      with a hypopigmented phenotype. Early diagnosis and appropriate management of
      these disorders can improve a patient's quality of life, halt disease
      progression, and prevent irreversible disability.

PMID- 30236515
TI  - In regards to Girard et a.l Occurrence of vismodegib-induced cramps (muscular
      spasms) in the treatment of basal cell carcinoma: A prospective study in 30
      patients.

PMID- 30236516
TI  - Acquired disorders with depigmentation: A systematic approach to vitiliginoid
      conditions.
AB  - Acquired disorders with depigmentation are commonly encountered by dermatologists
      and present with a wide differential diagnosis. Vitiligo, the most common
      disorder of acquired depigmentation, is characterized by well-defined depigmented
      macules and patches. Other conditions, such as chemical leukoderma, can present
      with similar findings, and are often easily mistaken for vitiligo. Key clinical
      features can help differentiate between acquired disorders of depigmentation.
      Part I of this two-part series focuses on conditions with a vitiligo-like
      phenotype. Early recognition and adequate treatment of these conditions is
      critical in providing appropriate prognostication and treatment.

PMID- 30236517
TI  - Pregnancy exposure to wind turbine noise and adverse birth outcomes: a nationwide
      cohort study.
AB  - Noise from wind turbines (WTs) is reported as more annoying than traffic noise at
      similar levels, raising concerns as to whether WT noise (WTN) may negatively
      affect health, as reported for traffic noise. We aimed to investigate whether
      residential WTN is associated with adverse birth outcomes. Based on national
      registries, we identified all Danish dwellings situated within <= 20 wt heights
      radius and a random selection of 25% of dwellings situated within 20-40 wt
      heights radius of a WT. We identified 135,795 pregnant women living in the
      dwellings from 1982 to 2013, and collected information on gestational age and
      birth weight from a national birth registry. Using data on WT type and simulated
      hourly wind at each WT, we estimated hourly outdoor and low frequency (LF) indoor
      WTN at the dwellings of the pregnant women and aggregated as mean nighttime WTN
      during pregnancy. We used logistic regression with adjustment for individual and
      area-level covariates for the analyses. We did not find evidence suggesting that
      mean pregnancy or trimester-specific exposure to outdoor or indoor LF WTN were
      associated with any of the three adverse birth outcomes investigated: preterm
      birth (n = 13,003), term small for gestational age (n = 12,220) or term low birth
      weight (n = 1127). However, the number of cases in the highest exposure
      categories of >= 42 dB outdoor WTN or >= 15 dB indoor LF WTN were low for all
      outcomes (n between 0 and 31). The present study does not support an association
      between nighttime WTN and adverse birth outcomes. However, there were few cases
      in the high exposure groups and the results call for reproduction.

PMID- 30236518
TI  - Bisphenol-A in breast adipose tissue of breast cancer cases and controls.
AB  - We evaluated whether bisphenol-A (BPA) could be quantified in breast adipose
      tissue samples provided by 36 breast cancer mastectomy patients and 14 reduction
      mammoplasty patients. Samples of breast adipose tissue were collected and BPA
      concentration was quantified using HPLC-ESI-MS/MS. BPA was detectable above the
      limit of quantitation of 0.38 ng/g in 30.6% of samples. BPA concentrations varied
      within- and between breasts and were similar between cases and controls (0.39 vs
      0.41 ng/g, p = 0.74).

PMID- 30236519
TI  - Stress axis variability is associated with differential ozone-induced lung
      inflammatory signaling and injury biomarker response.
AB  - Ozone (O3), a ubiquitous urban air pollutant, causes adverse pulmonary and
      extrapulmonary effects. A large variability in acute O3-induced effects has been
      observed; however, the basis for interindividual differences in susceptibility is
      unclear. We previously demonstrated a role for the hypothalamic-pituitary-adrenal
      (HPA) stress axis and glucocorticoid response in acute O3 toxicity.
      Glucocorticoids have important anti-inflammatory actions, and have been shown to
      regulate lung inflammatory responses. We hypothesised that a hyporesponsive HPA
      axis would be associated with greater O3-dependent lung inflammatory signaling.
      Two genetically-related rat strains with known differences in stress axis
      reactivity, highly-stress responsive Fischer (F344) and less responsive Lewis
      (LEW), were exposed for 4 h by nose-only inhalation to clean air or 0.8 ppm O3,
      and euthanized immediately after exposure. As expected, baseline (air-exposed)
      plasma corticosterone was significantly lower in the hypo-stress responsive LEW.
      Although O3 exposure increased plasma corticosterone in both strains,
      corticosterone remained significantly lower in LEW when compared to F334. LEW
      exhibited greater O3-induced inflammatory cytokine/chemokine signaling compared
      to F344, consistent with the lower corticosterone levels. Since we observed
      strain-specific differences in inflammatory signaling, we further investigated
      injury biomarkers (total protein, albumin and lactate dehydrogenase). Although
      the hyper-responsive F344 exhibited lower inflammatory signaling in response to
      O3 compared with LEW, they had greater levels of lung injury biomarkers. Our
      results indicate that stress axis variability is associated with differential O3
      induced lung toxicity. Given the large variability in stress axis reactivity
      among humans, stress axis regulation could potentially be a determining factor
      underlying O3 sensitivity.

PMID- 30236520
TI  - Effects of polychlorinated biphenyls (PCB) on California sea lion (Zalophus
      californianus) lymphocyte functions upon in vitro exposure.
AB  - Polychorinated biphenyl (PCB) congeners are a cause for concern due to their
      persistence in the environment, their lipophilic properties that cause them to
      bio-accumulate in top predators, and their adverse effects on mammalian health.
      For example, the common urogenital carcinoma reported in California sea lions
      (Zalophus californianus) (CSL) is associated with high tissue levels of PCBs, but
      the mechanisms responsible for this association are unknown. This study
      investigated the effect of exposure to six PCB congeners and a congener mix at
      low and environmentally relevant concentrations on NK cell-like and T cell
      activity using in vitro assays on cryopreserved lymph node mononuclear cells
      isolated from dead CSL. Non dioxin-like congeners 153 and 180 increased
      lymphocyte proliferation at 5 and 10 ppm, while congener 138 decreased
      proliferation by up to 43% at 15 ppm. Dioxin-like PCBs 118 and 169 did not affect
      lymphocyte proliferation, while the effects of congener 105 depended on the
      mitogen concentration; these did not correlate with their predicted toxic
      equivalent factors. NK cell-like activity was affected only by the highest
      concentration of PCBs tested; it was increased by non-dioxin-like congeners 138
      and 153, and decreased by dioxin-like congener 169. The PCB congener mix
      suggested that the effects of PCB congeners were not simply additive. Our results
      concur with effects of PCBs reported for other pinniped's lymphocytes and add
      further experimental support to the observation that dioxin-like PCBs are not the
      most toxic congeners for marine mammals, contrary to effects in other species.
      This is the first evidence of in vitro suppression of NK cell-like cytotoxicity
      by a dioxin-like congener in a pinniped. More importantly, the observed results
      suggest that PCBs can modulate the CSL immune system, increasing exposed
      individuals' susceptibility to viral and oncogenic challenges.

PMID- 30236522
TI  - PCR-coupled sequencing achieves specific diagnosis of onchocerciasis in a
      challenging clinical case, to underpin effective treatment and clinical
      management.
AB  - This study demonstrates the utility of a PCR-based DNA sequencing approach to
      make a specific diagnosis of onchocerciasis in a returned traveller. Although a
      clinical diagnosis was not possible, the surgical excision of a suprascapular
      nodule from this patient, combined with an histological examination of this
      nodule and PCR-based sequencing of DNA from a nematode from this lesion solved
      the case. The analysis of DNA sequence data confirmed the presence of Onchocerca
      volvulus infection, supporting an effective treatment-clinical management
      strategy for the patient.

PMID- 30236521
TI  - Environmental and take-home lead exposure in children living in the vicinity of a
      lead battery smelter in Serbia.
AB  - Blood lead levels (BLLs) have been falling steadily worldwide due to restricted
      use of lead (Pb) and its compounds. although they remain above preindustrial Pb
      levels. Elevated BLL can still be found in children living near secondary Pb
      smelters that represent around 50% of Pb production. There have been no studies
      on Pb exposure in children living in Serbia ever since the 1980s. The aim of this
      study was to evaluate the BLLs in children living in two villages in Serbia
      (Zajaca, the location of a secondary lead smelter, and Paskovac, 5 km away),
      identify the primary determinants of children's BLLs, and investigate the impact
      of BLLs on children's health symptoms and school achievement. The study was
      conducted in 2011 on 127 children, aged 1-18 years, whose BLLs were measured
      using inductively coupled argon plasma mass spectrometry (ICP-MS). The median BLL
      in children was 12 MUg/dl, with a significantly higher value of 17.5 MUg/dl in
      Zajaca, compared to 7.6 MUg/dl in Paskovac. Only 1 out of 75 and 12 out of 52
      children from Zajaca and Paskovac, respectively, had BLLs below the CDC
      recommended 5 MUg/dl level. Living near the smelter resulted in 19 times, and
      having a father who works in the plant 4 times higher odds of elevated BLLs. No
      significant effects of elevated BLLs health symptoms were seen in this study.
      BLLs of children living near a battery recycling plant in Serbia, an upper-middle
      income European country, were in the range and even higher than those of children
      living in developing countries. For the first time, the contribution of
      environmental and take-home lead exposure was quantified using mixed-effect
      modeling, and our results indicate a contribution of 25-40% of the take-home lead
      exposure to the BLLs of children living in the vicinity of a secondary lead
      smelter.

PMID- 30236523
TI  - Pirfenidone and Nintedanib in idiopathic pulmonary fibrosis: Real-life experience
      in an Italian referral centre.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis has a median survival time after
      diagnosis of 2-5 years. The main goal of treating IPF is to stabilize or reduce
      the rate of disease progression. Nintedanib and Pirfenidone have been a
      breakthrough in the management of IPF. Here we evaluated the effectiveness of
      Pirfenidone and Nintedanib in a population of IPF patients diagnosed in the last
      12 months at Florence ILD Referral Centre. METHODS: In the last 12 months, 82 IPF
      patients (66 male, mean age 78.3+/-23.8 years) were diagnosed and started
      antifibrotic therapy with Pirfenidone or Nintedanib. Their clinical and
      functional details were analyzed retrospectively at time 0 and after 6 and 12
      months of therapy. RESULTS: The median age of the patients treated with
      Nintedanib was higher than that of the Pirfenidone group (p<0.0001). The most
      common symptoms at disease onset were exertional dyspnoea and dry cough with no
      differences between the two groups (p<0.05). All IPF patients manifested bibasal
      crackles at the time of diagnosis. No significant differences in FVC, FEV1, TLC
      and DLCO were found at time 0 or after 6 months between patients treated with
      Pirfenidone and Nintedanib (p>0.05). After 1 year, lung function test parameters
      of patients treated with Pirfenidone had remained stable from baseline.
      DISCUSSION: This study emphasizes that both antifibrotic drugs appeared to be a
      good therapeutic choice in terms of functional stabilization, also in older
      patients.

PMID- 30236525
TI  - Independence between coping style and stress reactivity in plateau pika.
AB  - The concept of coping style represents the way individual animals react to a
      stressful situation, both behaviourally and neurophysiologically. Over the last
      decades coping style has been linked to the development of research on animal
      personality. Based on this concept, we should find a proactive-reactive continuum
      in animal populations, with proactive individuals being fast explorer, bold,
      aggressive, and show high sympathetic reactivity (higher heart rate), as well as
      low hypothalamus-pituitary-adrenocortical (PHA) axis reactivity to external
      stressor (higher plasma glucocorticoid level). At the other extreme, shy, lowly
      aggressive, reactive individuals should be slow in their exploration, and show a
      low sympathetic reactivity and a high HPA axis reactivity. However, a recent two
      tier model proposed that coping style and stress reactivity should be independent
      of each other. In this study, we tested the two-tier model in a wild plateau pika
      (Ochotona curzoniae) population on the Tibetan Plateau, by quantifying the
      associations between several behavioural and physiological traits at the among-
      and within-individual levels. We repeatedly measured exploration, docility,
      boldness, heart rate and plasma cortisol concentration in individuals between
      April and September of 2013. All traits tested were repeatable. At the among
      individual level, all behavioural traits were correlated with each other and with
      heart rate, but were independent of both basal level and variation of plasma
      cortisol concentration. Most correlations were negligible at the within
      individual level. In support of the two-tier model, these results suggest that
      coping style (i.e. behaviour and heart rate associations) is independent of
      stress reactivity (i.e. glucocorticoid reactivity) in that species.

PMID- 30236526
TI  - Associations between wellness and internal and external load variables in two
      intermittent small-sided soccer games.
AB  - The purpose of this study was to test the associations between wellness and
      internal and external load variables during two intermittent small-sided games
      (SSGs). Ten male amateur soccer players (age: 19.8+/-1.6 years; experience: 8.3+/
      2.1 years; height: 177.4+/-3.8 cm; weight: 71.7+/-4.2 kg) voluntarily
      participated in this study. The 5 * 5 format was played in 3 * 6 min and 6 * 3
      min regimens. Muscle soreness (DOMS), stress, fatigue, and sleep quality were
      rated before each session. Perceived exertion (RPE); mean heart rate (HRmean);
      total (TD), jogging (JD), running (RD), and sprinting (SD) distances; player's
      training load (PTL); and total accelerations (TAc) were monitored during SSGs. In
      the case of the 3 * 6' regimen, large negative correlations between DOMS and TD (
      0.68, [-0.89; -0.20]), JD (-0.66, [-0.89; -0.17]) and SD (-0.63, [-0.88; -0.12])
      were found, and very large negative correlations between DOMS and PTL (-0.84, [
      0.95; -0.53]) were found. Very large (-0.73, [-0.91; -0.30] and large (-0.61, [
      0.87; -0.09]) negative correlations between DOMS and HRmean and PTL,
      respectively, were observed during the 6 * 3' regimen. Regarding the associations
      between load variables, during the 6 * 3' regimen, RPE was very largely
      correlated with TD (0.77, [0.37; 0.93]), JD (0.70, [0.25; 0.90]) and largely
      correlated with TAc (0.67, [0.19; 0.89]). In the 3 * 6' regimen, large
      correlations were found between RPE and SD (0.62, [0.10; 0.87]) and TAc (0.61,
      [0.09; 0.87]). Overall, PTL was nearly perfectly correlated with TD (0.96, [0.86;
      0.99]) and JD (0.94, [0.81; 0.98]), very largely correlated with TAc (0.87,
      [0.61; 0.96]), and largely correlated with RD (0.72, [0.29; 0.91]). The results
      of this study suggest that wellness status may influence workload in SSGs; in
      particular, DOMS may be moderately-to-largely detrimental to both internal and
      external load variables. Moreover, it was confirmed that RPE is moderately-to
      largely correlated to objectively measured external load variables.

PMID- 30236524
TI  - ROS-related mitochondrial dysfunction in skeletal muscle of an ALS mouse model
      during the disease progression.
AB  - In amyotrophic lateral sclerosis (ALS), mitochondrial dysfunction and oxidative
      stress form a vicious cycle that promotes neurodegeneration and muscle wasting.
      To quantify the disease-stage-dependent changes of mitochondrial function and
      their relationship to the generation of reactive oxygen species (ROS), we
      generated double transgenic mice (G93A/cpYFP) that carry human ALS mutation
      SOD1G93A and mt-cpYFP transgenes, in which mt-cpYFP detects dynamic changes of
      ROS-related mitoflash events at individual mitochondria level. Compared with wild
      type mice, mitoflash activity in the SOD1G93A (G93A) mouse muscle showed an
      increased flashing frequency prior to the onset of ALS symptom (at the age of 2
      months), whereas the onset of ALS symptoms (at the age of 4 months) is associated
      with drastic changes in the kinetics property of mitoflash signal with prolonged
      full duration at half maximum (FDHM). Elevated levels of cytosolic ROS in
      skeletal muscle derived from the SOD1G93A mice were confirmed with fluorescent
      probes, MitoSOXTM Red and ROS BriteTM570. Immunoblotting analysis of subcellular
      mitochondrial fractionation of G93A muscle revealed an increased expression level
      of cyclophilin D (CypD), a regulatory component of the mitochondrial permeability
      transition pore (mPTP), at the age of 4 months but not at the age of 2 months.
      Transient overexpressing of SOD1G93A in skeletal muscle of wild type mice
      directly promoted mitochondrial ROS production with an enhanced mitoflash
      activity in the absence of motor neuron axonal withdrawal. Remarkably, the
      SOD1G93A-induced mitoflash activity was attenuated by the application of
      cyclosporine A (CsA), an inhibitor of CypD. Similar to the observation with the
      SOD1G93A transgenic mice, an increased expression level of CypD was also detected
      in skeletal muscle following transient overexpression of SOD1G93A. Overall, this
      study reveals a disease-stage-dependent change in mitochondrial function that is
      associated with CypD-dependent mPTP opening; and the ALS mutation SOD1G93A
      directly contributes to mitochondrial dysfunction in the absence of motor neuron
      axonal withdrawal.

PMID- 30236528
TI  - Less "Tradition," More New Technologies or Vice Versa?

PMID- 30236527
TI  - Preoperative Venoarterial Extracorporeal Membrane Oxygenation Slashes Risk Score
      in Advanced Structural Heart Disease.
AB  - BACKGROUND: Cardiac surgery for structural heart disease has poor outcomes in the
      presence of cardiogenic shock or advanced heart failure. We applied venoarterial
      extracorporeal membrane oxygenation (ECMO) to restore end-organ function and
      resuscitate patients before high-risk cardiac operation. METHODS: Twelve patients
      with cardiogenic shock and end-organ failure were evaluated for cardiac surgery.
      The average Society of Thoracic Surgeons mortality risk was 24% +/- 13%. Patients
      were peripherally cannulated on ECMO for 7 +/- 4 days, before undergoing
      operation for prosthetic mitral stenosis (n = 4), ruptured papillary muscle (n =
      4), ischemic ventricular septal defect (n = 3), or severe aortic stenosis (n =
      1). RESULTS: Mean age was 61 +/- 8 years. Comorbidities included acute renal
      failure (n = 11), inotrope requirement (n = 10), intraaortic balloon pump (n =
      8), severe acidosis (n = 6), high-dose vasopressor requirement (n = 8), and
      cardiac arrest (n = 1). With ECMO support, vasopressor requirement, central
      venous pressure, creatinine, lactate, pH, pulmonary hypertension, and The Society
      of Thoracic Surgeons mortality risk and EuroSCORE (European System for Cardiac
      Operative Risk Evaluation) II all improved significantly. Care was withdrawn in 1
      patient on ECMO with initially unknown anoxic brain injury. No patients required
      dialysis at discharge. Complications included 1 permanent stroke. All operative
      patients survived to hospital discharge. Average length of follow-up was 420
      days, with 2 patient deaths at 76 and 230 days and 6 patients surviving over 1
      year. CONCLUSIONS: ECMO can be used as a bridge to heart valve or septal defect
      surgery in severely decompensated patients. Through recovery of end-organ
      function, ECMO may allow surgical correction of structural heart disease in
      patients considered inoperable or convert a salvage situation to an elective
      operation.

PMID- 30236529
TI  - Drug susceptibility patterns of Mycobacterium abscessus and Mycobacterium
      massiliense isolated from respiratory specimens.
AB  - In this study, we aimed to retrospectively investigate and compare the drug
      susceptibility patterns of two major Mycobacterium abscessus complex (MABC)
      species; M. abscessus and M. massiliense. A total of 546 MABC respiratory
      isolates (277 M. abscessus and 269 M. massiliense) from 2011 to 2016 were
      analyzed in this study. We estimated minimum inhibitory concentrations (MICs)
      using the broth microdilution method, and we calculated MIC50 and MIC90 values
      from the MIC distribution. Both M. abscessus and M. massiliense were highly
      susceptible to amikacin and linezolid. For M. abscessus, the proportions of
      inducible and acquired resistance to clarithromycin were 68.6% and 12.3%,
      respectively. Only 15.2% of M. abscessus remained susceptible at day 14. On the
      other hand, none of the M. massiliense showed inducible resistance and 6.3%
      showed acquired resistance to clarithromycin. A total of 92.6% of the M.
      massiliense remained susceptible at day 14. The resistance rate of M. abscessus
      to moxifloxacin (90.3%) was significantly higher than that of M. massiliense
      (83.3%; p = 0.016). These susceptibility differences may explain the divergent
      treatment outcomes between patients with pulmonary disease caused by these two
      species.

PMID- 30236530
TI  - Activity of fosfomycin when tested against US contemporary bacterial isolates.
AB  - Fosfomycin and comparators were susceptibility tested against over 2200
      contemporary clinical isolates from US medical centers. Fosfomycin was active
      against Enterobacterales (MIC50/90, 4/16 MUg/mL), including multidrug-resistant
      isolates. Potent activity was exhibited against gram-positive organisms,
      including Staphylococcus aureus (MIC50/90, 4/8 MUg/mL). Fosfomycin may provide a
      promising alternative option for treatment of infections where resistant bacteria
      may occur.

PMID- 30236531
TI  - MERS: Progress on the global response, remaining challenges and the way forward.
AB  - This article summarizes progress in research on Middle East Respiratory Syndrome
      (MERS) since a FAO-OIE-WHO Global Technical Meeting held at WHO Headquarters in
      Geneva on 25-27 September 2017. The meeting reviewed the latest scientific
      findings and identified and prioritized the global activities necessary to
      prevent, manage and control the disease. Critical needs for research and
      technical guidance identified during the meeting have been used to update the WHO
      R&D MERS-CoV Roadmap for diagnostics, therapeutics and vaccines and a broader
      public health research agenda. Since the 2017 meeting, progress has been made on
      several key actions in animal populations, at the animal/human interface and in
      human populations. This report also summarizes the latest scientific studies on
      MERS since 2017, including data from more than 50 research studies examining the
      presence of MERS-CoV infection in dromedary camels.

PMID- 30236532
TI  - Improving the clinical relevance of a mouse pregnancy model of antiretroviral
      toxicity; a pharmacokinetic dosing-optimization study of current HIV
      antiretroviral regimens.
AB  - Animal models can be useful tools for the study of HIV antiretroviral (ARV)
      safety/toxicity in pregnancy and the mechanisms that underlie ARV-associated
      adverse events. The utility and translatability of animal model-based ARV
      safety/toxicity data is improved if ARVs are tested in clinically relevant
      concentrations. The objective of this work was to improve the clinical relevance
      of our mouse pregnancy model of ARV toxicity, by determining the doses of
      currently prescribed ARV regimens that would yield human therapeutic plasma
      concentrations. Pregnant mice were administered increasing doses of ARV
      combinations by oral gavage, followed by measurement of drug concentrations in
      the maternal plasma and amniotic fluid. Concentrations of ten different ARVs in
      maternal plasma and amniotic fluid samples of pregnant mice are presented, with
      dosing optimization to yield human pregnancy-relevant plasma drug concentrations.
      We have proposed optimal dosing for different regimen component drugs to achieve
      human therapeutic plasma levels, so that a clinically relevant standard dosing is
      established. A review of related ARV pharmacokinetic studies in (pregnant/non
      pregnant) rodents and human pregnancy is also shown. We hope these data will
      inform and encourage the use of mouse pregnancy models in the study of ARV
      safety/toxicity.

PMID- 30236533
TI  - Depression and adult neurogenesis: Positive effects of the antidepressant
      fluoxetine and of physical exercise.
AB  - Of wide interest for health is the relation existing between depression, a very
      common psychological illness, accompanied by anxiety and reduced ability to
      concentrate, and adult neurogenesis. We will focus on two neurogenic stimuli,
      fluoxetine and physical exercise, both endowed with the ability to activate adult
      neurogenesis in the dentate gyrus of the hippocampus, known to be required for
      learning and memory, and both able to counteract depression. Fluoxetine belongs
      to the class of selective serotonin reuptake inhibitor (SSRI) antidepressants,
      which represent the most used pharmacological therapy; physical exercise has also
      been shown to effectively counteract depression symptoms in rodents as well as in
      humans. While there is evidence that the antidepressant effect of fluoxetine
      requires its pro-neurogenic action, exerted by promoting proliferation,
      differentiation and survival of progenitor cells of the hippocampus, on the other
      hand fluoxetine exerts also neurogenesis-independent antidepressant effects by
      influencing the plasticity of the new neurons generated. Similarly, the
      antidepressant action of running also correlates with an increase of hippocampal
      neurogenesis and plasticity, although the gene pathways involved are only
      partially coincident with those of fluoxetine, such as those involved in
      serotonin metabolism and synapse formation. We further discuss how extra
      neurogenic actions are also suggested by the fact that, unlike running,
      fluoxetine is unable to stimulate neurogenesis during aging, but still displays
      antidepressant effects. Moreover, in specific conditions, fluoxetine or running
      activate not only progenitor but also stem cells, which normally are not
      stimulated; this fact reveals how stem cells have a long-term, hidden ability to
      self-renew and, more generally, that neurogenesis is subject to complex controls
      that may play a role in depression, such as the type of neurogenic stimulus or
      the state of the local niche. Finally, we discuss how fluoxetine or running are
      effective in counteracting depression originated from stress or neurodegenerative
      diseases.

PMID- 30236534
TI  - Maternal exposure to fluoxetine during gestation and lactation induces long
      lasting changes in the DNA methylation profile of offspring's brain and affects
      the social interaction of rat.
AB  - Fluoxetine (FLX) is an antidepressant from the selective serotonin reuptake
      inhibitor class that has largely been used for the treatment of depression in
      pregnancy. However, increasing evidences have indicated the potential of early
      maternal exposure to FLX to induce molecular and neuro functional effects on the
      offspring. In the present study we evaluated possible long lasting impacts of the
      maternal exposure to FLX during gestation and lactation. Female Wistar rats were
      gavaged with 5 mg/kg of FLX during the period that comprehends the first day of
      pregnancy (PD0) and the last day of lactation (LD21) (Group FLX). Control group
      (CTL) received a proportional volume of water. On the postnatal day 75 (PND75),
      male rats were euthanized and hippocampus, cortex, hypothalamus, and
      periaqueductal gray area (PAG) were removed. Global DNA methylation was
      quantified using a high-throughput ELISA-based method. In order to address neuro
      functional changes animals (PND75) were evaluated in the elevated plus maze and
      social interaction tests as well as submitted to repeated restraint stress. An
      increase in the global DNA methylation profile of hippocampus (p = 0.0399) was
      associated with the early exposure to FLX, whereas no significant change was
      observed in the hypothalamus (p = 0.6556), cortex (p = 0.9402) or PAG (p =
      0.3822). Furthermore, early exposure to FLX was also associated with a reduction
      in the social interaction time (p = 0.0084) and to a decreased in the plasma
      corticosterone level when animals were submitted to the restraint stress (p <
      0.0001). No significant change in the elevated plus maze test was associated with
      the early exposure to FLX. In summary, our data demonstrate that maternal
      exposure to FLX during gestation and lactation results in a long lasting impact
      on the DNA methylation of hippocampus, and affects the social behavior and the
      corticosterone response to stress.

PMID- 30236535
TI  - Investigation of the Effectiveness of a Holistic Vocal Training Program Designed
      to Preserve Theatre Students' Vocal Health and Increase Their Vocal Performances;
      A Prospective Research Study.
AB  - OBJECTIVE: The main purpose of this study is to investigate the effectiveness of
      a 12-week holistic vocal training program designed for theatre students. METHODS:
      The participants included 10 female and 8 male students, who were third- and
      fourth-year students of a state conservatory theatre department. Participants
      randomly selected from among those who were between the ages of 18-30years, had
      no history of voice disorders, and had no systemic and neurological disorders.
      The study group (n = 9) was involved in the vocal training program. The control
      group (n = 9) has not received any training. During the program, 12 sessions of
      lectures and voice exercises were given to all participants of the study group
      for a period of 12 weeks. The sessions were planned to last for a duration of 30
      45 minutes. Participants' knowledge of vocal health was assessed using a
      questionnaire that was developed in the present study and a multidimensional
      voice assessment protocol including acoustic analyses and audio-perceptual
      evaluation has been applied. RESULTS: Within-group comparisons indicated a
      significant increase in the study group participants' knowledge of vocal hygiene
      after training (P = 0.011). Similarly, the study group outperformed the control
      group in the vocal mechanism knowledge (P = 0.027). Multidimensional Voice
      Profile findings revealed that vocal qualities of the control group deteriorated,
      whereas no alterations were found in the study group. Audio-perceptual analysis
      conducted through the Consensus Auditory-Perceptual Evaluation of Voice did not
      introduce significant changes in the control group in overall severity and
      roughness parameters, these values were found significantly improved for the
      study group. CONCLUSION: It can be concluded that the Holistic Vocal Training
      Program designed in the present study is effective for preserving theatre
      students' vocal health and voice quality. It is important for future studies to
      search the long-term effects.

PMID- 30236536
TI  - A Comparison of Laboratory and Virtual Laryngeal Dissection Experiences on
      Preservice Music Educators' Knowledge and Perceptions.
AB  - Science-education literature is replete with studies examining how students learn
      anatomy most effectively and efficiently. Some researchers have found that
      students learn best through hands-on learning, whereas other investigators have
      concluded students rate both computer and hands-on learning as effective and
      enjoyable. No study to date, however, has examined anatomical learning of
      preservice music education students on anatomical and physiological knowledge of
      the larynx. Therefore, the purpose of this investigation was to examine the
      effectiveness of virtual versus laboratory dissection in learning anatomy of the
      laryngeal structure for preservice music educators in a vocal pedagogy course.
      University students (N = 26) were given a pretest on laryngeal physiology and
      anatomy. Thereafter, the first group (n = 13) attended five 1-hour sessions of
      laryngeal dissection in a cadaver lab. The second group (n = 13) attended five 1
      hour sessions in a computer lab equipped with Physiology and Anatomy Revealed,
      version 3.0 (McGraw Hill, New York, NY), a computer software program designed to
      simulate the dissection experience. Two days after finishing the laboratory or
      virtual dissection experience, each group was given a posttest. Perceptions were
      also gathered through a short questionnaire following the posttest. Results
      indicated that student knowledge and perceptions varied widely. All participants
      showed improved scores from pre- to posttest measures; however, scores were not
      significantly different between groups. Results are discussed in terms of
      feasibility of such a learning mode and importance of dissection experiences in
      understanding human anatomy as well impact on future music educators' teaching
      practice.

PMID- 30236537
TI  - Translation and Validation of Tamil Version of Singing Voice Handicap Index-10
      (TSVHI-10).
AB  - AIM: To translate and validate the singing voice handicap index (SVHI-10) for the
      Tamil speaking Indian population and to evaluate the psychometric properties of
      the Tamil version SVHI-10 (TSVHI-10) in classically trained Carnatic singers.
      METHOD: Following standard translation, a total of 120 classically trained
      Carnatic singers: 83 singers without voice complaint and 37 singers with voice
      complaints answered the Tamil translation of the SVHI-10. RESULTS: The TSVHI -10
      scores obatined from classically trained Carnatic singers with and singers
      without voice complaints were analyzed. SVHI-10 has excellent internal
      consistency and test retest reliability. Singers without/with voice complaint
      scored 7.08/22.86 total scores and for each domain Emotional (E): 1.73/5.32,
      Functional (F): 2.11/7.08, and Physical (P): 3.3/10.35 respectively. CONCLUSION:
      The TSVHI-10 questionnaire seems to be psychometrically sound and is a valuable
      instrument for the self-evaluation of handicaps related to voice problems in the
      context of singing and for making subsequent clinical decisions. The Tamil
      version of the SVHI-10 was successfully validated as an instrument with proper
      internal consistency and reliability.

PMID- 30236538
TI  - Pediatric Dysphonia: A Cross-Sectional Survey of Subspecialty and Primary Care
      Clinics.
AB  - OBJECTIVES: Prevalence data for pediatric dysphonia are sparse and primarily
      collected either in the community or within pediatric otolaryngology clinics. The
      objectives were to determine the prevalence of dysphonia in children undergoing
      outpatient medical evaluation, and to ascertain whether the prevalence varies
      across pediatric subspecialty clinic populations in comparison to primary care.
      STUDY DESIGN: Cross-sectional survey. SETTING: Tertiary care military medical
      center. SUBJECTS AND METHODS: Five hundred sixteen surveys were administered to
      caregivers of children undergoing evaluation in pediatric primary care and
      subspecialty clinics consisting of the pediatric voice-related quality of life
      (PVRQOL) instrument and questions regarding previous voice-related symptoms and
      diagnoses. Survey responses and PVRQOL scores were stratified by clinic type and
      compared to general pediatrics. RESULTS: A total of 492 surveys were analyzed.
      The overall prevalence of dysphonia in this cohort based on PVRQOL is 19.3%.
      Every clinic except endocrinology and ophthalmology individually had an elevated
      prevalence compared to the expected community prevalence (11%). Compared to
      general pediatrics, PVRQOL scores were lower in developmental pediatrics (P <
      0.001), genetics (P < 0.001), and otolaryngology (P = 0.033) clinics. Children
      from genetics and developmental pediatrics were more likely to have had speech
      therapy. CONCLUSIONS: In this cohort of children seeking care within a medical
      center, overall prevalence of dysphonia was quite high in comparison to community
      based prevalence data. Not surprisingly, patients of developmental pediatrics,
      genetics and pediatric otolaryngology have lower PVRQOL scores than primary care.
      These results emphasize that all practitioners caring for children should seek to
      identify voice disorders and reinforce that subspecialists who treat
      developmentally challenged children should exert particular vigilance.

PMID- 30236539
TI  - Performance of the point-of-care circulating cathodic antigen (POC-CCA) urine
      cassette test for follow-up after treatment of S. mansoni infection in Eritrean
      refugees.
AB  - BACKGROUND: Point-of-care circulating cathodic antigen (POC-CCA) urine cassette
      testing has become a popular approach to screen for Schistosoma infection. Since
      the test is also increasingly used for following-up of treatment success, we
      assessed the assay's diagnostic accuracy after praziquantel treatment of S.
      mansoni infection among Eritrean refugees in Switzerland. METHODS: In our
      preceding study, 107 asymptomatic Eritrean refugees in Switzerland were screened
      for schistosomiasis by stool microscopy, serology, and POC-CCA urine testing.
      Individuals screened positive by any method were treated with praziquantel and
      invited for a follow-up visit, repeating the same diagnostic procedures one year
      after treatment. The POC-CCA baseline and follow-up results were analyzed against
      the 'baseline microscopy positive cases' (= the most reliably true positive
      cases) and the 'baseline microscopy plus serology negative cases at baseline and
      follow-up' (= the most reliably true negative cases). RESULTS: Complete
      diagnostic baseline and follow-up sampling was available from 48 participants.
      Compared to most reliably true positive cases at baseline, POC-CCA testing had a
      sensitivity of 90%. Compared to most reliably true negative cases, POC-CCA
      testing had a specificity of 73.9%. CONCLUSION: We conclude that the POC-CCA
      urine test is valuable for screening but its use is not suitable for routine
      follow-up after treatment.

PMID- 30236540
TI  - Bakuchiol exhibits anti-metastasis activity through NF-kappaB cross-talk
      signaling with AR and ERbeta in androgen-independent prostate cancer cells PC-3.
AB  - Androgen-independent prostate cancer (PCa) is a developed tumor derived from the
      local androgen dependent PCa, which often affects elderly men. Psoralea
      corylifolia L, a traditional Chinese medicine, has been widely used for PCa
      treatment as an important part of a common prescription, while the mechanism
      remains unclear. Our study was aimed to investigate the tumor-inhibitory effect
      of its main component bakuchiol in androgen-independent PCa cell line PC-3 cells.
      Bakuchiol significantly suppressed PC-3 cell proliferation and migration; the
      expressions of PCNA and MMP-9 were consistently down regulated as well.
      Meanwhile, both the constitutive and LPS-induced NF-kappaB activation were
      significantly inhibited by bakuchiol. The inhibitory effects of bakuchiol on cell
      proliferation, migration and invasion were recovered when LPS were added together
      with bakuchiol. SiRNA against androgen receptor (AR) or estrogen receptor beta
      (ERbeta) were transfected and the regulation of bakuchiol-suppressed
      proliferation, invasion, NF-kappaB signaling and MMP-9 secretion in response to
      LPS were blocked. Taken together, our data demonstrated that bakuchiol
      inactivated NF-kappaB signaling via AR and ERbeta, which contributes to
      inhibition of PC-3 cell proliferation and migration, indicating that bakuchiol is
      one of the key component from P. corylifolia L for PCa treatment and has a
      potential as anti-prostate cancer drug candidates.

PMID- 30236541
TI  - The differential impact of adverse childhood experiences in the development of
      pre-diabetes in a longitudinal cohort of US adults.
AB  - BACKGROUND: ACEs have a dose-response relationship with diabetes. The
      relationship between ACEs and pre-diabetes is not well known and may represent an
      effective area for prevention efforts. METHODS: Data from 1054 participants from
      two waves of the longitudinal MIDUS study were used. Multivariate general linear
      regression models assessed the relationship between ACEs and biomarker outcomes.
      Correlation tests and mediation models investigated the relationship between ACE
      and pre-diabetes. RESULTS: Individuals reporting ACEs were statistically
      significantly more likely to have higher BMI (1.13 (0.34-1.92)), higher waist
      circumference (2.74 (0.72-4.76)), elevated blood fasting insulin levels (2.36
      (0.71-4.02)) and higher insulin resistance (HOMA-IR (0.57 (0.08-1.06)). BMI/waist
      circumference and insulin resistance did not maintain independent relationships
      with ACEs once HOMA-IR was included in the dichotomized ACE model (p = 0.05 and p
      = 0.06, respectively), suggesting the relationship between BMI and ACEs may be
      mediated by insulin resistance. CONCLUSIONS: These results represent one of the
      first studies to examine the differential impact of ACEs on a diverse set of
      clinical pre-diabetes measures. Findings suggest sexual and physical abuse, and
      financial strain during childhood are important factors associated with higher
      risk for pre-diabetes, and should be considered during intervention development.

PMID- 30236542
TI  - Design and validation of a novel estimator of visceral adipose tissue area and
      comparison to existing adiposity surrogates.
AB  - AIMS: Visceral adiposity measured by computed tomography (CT) as intra-abdominal
      fat area (IAFA) predicts metabolic diseases. Existing adiposity surrogates have
      not been systematically compared to a regression-based model derived in
      individuals of Japanese ancestry. We developed and validated a method to estimate
      IAFA in individuals of Japanese ancestry and compared it to existing adiposity
      surrogates. METHODS: We assessed age, BMI, waist circumference (WC), fasting
      lipids, glucose, smoking status, grip strength, mid-thigh circumference (MTC),
      humeral length, leg length, and IAFA by single-slice CT at the umbilicus for 622
      Japanese Americans. We used stepwise linear regression to predict IAFA and termed
      the predicted value the Estimate of Visceral Adipose Tissue Area (EVA). For men,
      the final model included age, BMI, WC, high-density lipoprotein cholesterol
      (HDLc), glucose, and MTC; for women, age, BMI, WC, HDLc, low-density lipoprotein
      cholesterol, glucose, and MTC. We compared goodness-of-fit (R2) from linear
      regression models and mean-squared errors (MSE) from k-fold cross-validation to
      compare the ability of EVA to estimate IAFA compared to an estimate by Despres et
      al., waist-to-height ratio, WC, deep abdominal adipose tissue index, BMI, lipid
      accumulation product, and visceral adiposity index (VAI). We classified low/high
      IAFA using area under receiver-operating characteristic curves (AUROC) for IAFA
      dichotomized at the 75th percentile. RESULTS: EVA gave the least MSE and greatest
      R2 (men: 1244, 0.61; women: 581, 0.72). VAI gave the greatest MSE and smallest R2
      (mean 2888, 0.08; women 1734, 0.14). CONCLUSIONS: EVA better predicts IAFA in
      Japanese-American men and women compared to existing surrogates for adiposity.

PMID- 30236544
TI  - High-grade myoepithelial carcinoma can show histologically
      undifferentiated/anaplastic features.
AB  - High grade malignant tumors with a poorly-/un-differentiated morphology pose
      significant diagnostic challenges. Increasingly, the use of adjunct
      immunohistochemical and molecular tests to characterize and delineate the
      histopathologic phenotype of these tumors has become necessary, particularly in
      head and neck tumors. Recently, several entities with a poorly-/un-differentiated
      light microscopic morphology have been defined based on specific
      immunohistochemical and genetic characteristics. We herein describe two cases of
      high-grade myoepithelial carcinoma, one occurring in the submandibular gland and
      the other occurring in the left nasal cavity, both showing undifferentiated
      histological and anaplastic cytomorphological features. This led to very broad
      differential diagnostic considerations and the diagnosis was only established
      after extensive immunohistochemical studies. Molecular testing for HPV was
      negative in both cases. Gene fusion analysis using a targeted sequencing assay
      (Archer(r) FusionPlex(r) system) did not identify fusions involving PLAG1, HMGA2,
      EWSR1 or ALK genes in either case. The submandibular tumor showed an aggressive
      clinical course, with diffuse pulmonary metastases at presentation, whilst the
      nasal cavity tumor showed only localized disease. Awareness of a subcategory of
      high-grade myoepithelial carcinomas with undifferentiated light microscopical
      features is of significant importance in antibody selection for
      immunohistochemical investigation of poorly-/undifferentiated malignant tumors in
      the head and neck region. This histological variant of myoepithelial carcinoma
      adds to the growing list of differential diagnoses in this diagnostically complex
      and multifaceted field.

PMID- 30236543
TI  - Association between nonalbumin proteinuria and renal tubular damage of N-acetyl
      beta-d-glucosaminidase and its clinical relevance in patients with type 2
      diabetes without albuminuria.
AB  - AIM: Although albuminuria and urinary N-acetyl-beta-d-glucosaminidase (uNAG) are
      known as progression markers of diabetic kidney disease, there is limited
      information regarding the association between urinary nonalbumin proteinuria
      (NAP) and uNAG and the clinical relevance thereof in patients without
      albuminuria. METHODS: This cross-sectional study included samples from 244
      consecutive patients with type 2 diabetes mellitus (T2D) without albuminuria.
      Proteinuria and albuminuria were defined according to protein-to-creatinine ratio
      (uPCR) and albumin-to-creatinine ratio (uACR), respectively. NAP was indirectly
      calculated by the difference between uPCR and uACR. RESULTS: NAP and uNAG
      excretion were significantly correlated (r = 0.525, P < 0.001). Individuals whose
      NAP levels were in the highest tertile had a longer duration of diabetes,
      uncontrolled hyperglycemia, and impaired insulin stimulation (all P < 0.05),
      although more patients in the highest NAP tertile were prescribed insulin and
      sulfonylurea. Multiple linear regression analyses revealed associations among
      uNAG, diabetes duration, and waist circumference. CONCLUSIONS: T2D patients
      without albuminuria excrete proteinuria and that presence of the protein in urine
      is associated with uNAG. NAP was positively correlated with T2D duration and
      waist circumference, but negatively correlated with body mass index. Lean, but
      centrally obese, T2D patients in late diabetes experience more tubular damage,
      regardless of the presence of albuminuria.

PMID- 30236545
TI  - Assessment of transurethral resection of the bladder specimens with pT1 high
      grade urothelial carcinoma for the predictor features of muscularis propria
      invasion on radical cystectomy specimens.

PMID- 30236546
TI  - The expression of TTF1, CDX2 and ISL1 in 74 poorly differentiated neuroendocrine
      carcinomas.
AB  - BACKGROUND: The expression profile of immunohistochemical markers of origin in
      poorly differentiated neuroendocrine carcinoma (PDNEC) is not well studied.
      MATERIALS AND METHODS: Seventy-four PDNECs from gastroenteropancreatic (GEP)
      organs and the lung, including 48 large cell NEC (LCNEC) and 26 small cell
      carcinomas (SmCC), were subject to immunohistochemical staining for CDX2, TTF1
      and ISL1. The staining intensity (1 to 3) and percentage of positive tumor cells
      [0 (negative), 1 (<50%) and 2 (>=50%)] were assessed. The multiplicative index
      (maximum 6) was calculated and the average total score (aTS) was determined for
      each primary site and histologic subtype. RESULTS: In the 38 GEP and 36 lung
      PDNECs, CDX2, TTF1 and ISL1 staining was observed in 71% (aTS 2.8), 16% (aTS
      0.4), 63% (aTS 1.9), and 22% (aTS 0.6), 72% (aTS 2.9) and 92% (aTS 3.8),
      respectively. GEP PDNECs showed a higher aTS for CDX2 and lower aTS for TTF1 and
      ISL1, compared to that of lung PDNECs (Student's t-test, p < 0.001). SmCC had a
      higher aTS for TTF1 and ISL1 (p < 0.001) and lower aTS for CDX2 (p < 0.002) than
      that of LCNEC. CONCLUSIONS: CDX2 and TTF1 demonstrate potential utility in
      suggesting the primary site of PDNEC. In addition, CDX2 may be useful in
      supporting the diagnosis of LCNEC in cases with overlapping or borderline
      morphology. Utility of ISL1 as an adjunctive diagnostic marker of SmCC remains to
      be studied.

PMID- 30236547
TI  - Association of autonomic symptoms with presynaptic striatal dopamine depletion in
      drug-naive Parkinson's disease: An analysis of the PPMI data.
AB  - While the involvement of the central and peripheral autonomic networks is thought
      to play an integral role in the development of autonomic symptoms in Parkinson's
      disease (PD), there is little evidence for an association between autonomic
      symptoms and striatal dopaminergic depletion. We compared dopamine transporter
      activity in striatal subregions with various autonomic symptoms covered by the
      SCOPA-AUT domains including gastrointestinal, urinary, cardiovascular,
      thermoregulatory, pupillomotor, and sexual symptoms in 418 untreated patients
      with PD. We found evidence for a dopaminergic association with only urinary
      symptoms. Moreover, dopaminergic denervation in the putamen but not in the
      caudate may underlie these symptoms.

PMID- 30236548
TI  - Caregiver Perceptions about their Decision to Pursue Tracheostomy for Children
      with Medical Complexity.
AB  - OBJECTIVE: To describe the perceptions of caregivers of children with medical
      complexity (CMC) about their decision to pursue tracheostomy for their children,
      in particular the satisfaction with their decision. STUDY DESIGN: In this
      qualitative study conducted in western North Carolina between 2013 and 2014, we
      interviewed 56 caregivers of 41 CMC who had received tracheostomies in the past 5
      years. Three of the CMC were deceased at the time of the interview; 8 were
      decannulated. In-depth interviews (35 English, 6 Spanish) were conducted, audio
      recorded, and transcribed verbatim. We used ATLAS.ti software to manage data and
      identified themes related to caregiver perceptions about tracheostomy decision.
      RESULTS: We found that caregivers often chose tracheostomy because extending the
      lives of their children and being able to care for them at home were important.
      Caregivers reported the many benefits of tracheostomy including improvement in
      respiratory symptoms, physical and developmental health, quality of life, and
      means to provide medical care quickly when needed. There were negative effects of
      tracheostomy such as mucous plugs, excessive secretions, accidental decannulation
      necessitating emergency tracheostomy tube change, and the increased infection
      risk. Providing medical care for CMC with tracheostomy at home was difficult, but
      improved over time. Caregivers were generally satisfied with their decision to
      pursue tracheostomy for their CMC. CONCLUSIONS: Decisional satisfaction with
      tracheostomy for CMC is high. In counseling caregivers about tracheostomy,
      clinicians should present both the benefits and risks. Future studies should
      quantify the outcomes described in this study.

PMID- 30236549
TI  - Systematic review of progressive familial intrahepatic cholestasis.
AB  - BACKGROUND AND AIMS: Progressive familial intrahepatic cholestasis (PFIC) is a
      heterogeneous group of rare genetic disorders associated with bile acid secretion
      or transport defects. This is the first systematic review of the epidemiology,
      natural history and burden of PFIC. METHODS: MEDLINE and Embase were searched for
      publications on PFIC prevalence, incidence or natural history, and the economic
      burden or health-related quality of life (HRQoL) of patients with PFIC. Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines were
      followed. RESULTS: Of 1269 records screened, 20 were eligible (epidemiology, 17;
      humanistic burden, 5; both, 2). Incidence of intrahepatic cholestasis, including
      but not limited to PFIC, was 1/18 000 live births in one study that did not use
      genetic testing. In two studies of infants and children (2-18 years) with
      cholestasis, 12-13% had genetically diagnosed PFIC. Of the three main PFIC
      subtypes, PFIC2 was the most common (21-91% of patients). Common symptoms (e.g.
      pruritus, jaundice, hepatomegaly, splenomegaly) generally appeared at about 3
      months of age and tended to emerge earliest in patients with PFIC2. Patients
      reported that pruritus was often severe and led to dermal damage and reduced
      HRQoL. Disease progression led to complications including liver failure and
      hepatocellular carcinoma, with 20-83% of patients requiring liver
      transplantation. Mortality was 0-87% across 10 studies (treatment varied among
      studies), with a median age at death of ~4 years in one study. CONCLUSIONS:
      Patients with PFIC face debilitating symptoms and poor prognosis. Further
      research is needed to inform patient management and clinical trial design.
      Published data on the epidemiology and socioeconomic burden of PFIC is limited.

PMID- 30236550
TI  - Topical treatment with a transient receptor potential ankyrin 1 (TRPA1)
      antagonist reduced nociception and inflammation in a thermal lesion model in
      rats.
AB  - Thermal injury promotes tissue inflammation and pain, which is difficult to
      control. Different peripheral mechanisms seem to be involved in burn pain, such
      as free radical-induced damage, but further study is still needed to understand
      how oxidant substances induced nociceptor sensitization. The transient receptor
      potential ankyrin 1 (TRPA1) is an ion channel activated by oxidants substances,
      and it could be sensitized after tissue inflammation. This study evaluated the
      TRPA1 involvement in nociception and inflammation produced by a thermal injury
      model. Male Wistar rats were used. The concentration of the TRPA1 antagonist (HC
      030031, 0.05%) on base cream was chosen using allyl isothiocyanate intraplantar
      test. Then, the base cream containing HC-030031 was tested on the thermal injury
      model (induced by warm water immersion of hind paw, under anesthesia), and silver
      sulfadiazine (1%) was used as a positive control. Cream treatments on the hind
      paw were done daily (200 mg/paw) for 6 days after thermal injury. Also,
      nociception (static and dynamic mechanical allodynia, heat allodynia, and
      spontaneous pain) or edema were evaluated. On day 6, inflammatory and oxidative
      parameters were assessed. The base cream containing HC-030031 produced
      antinociceptive and anti-inflammatory effects (reduced the edema and inflammatory
      cells infiltration) and decreased the levels of hydrogen peroxide, or superoxide
      dismutase and NADPH oxidase activities after thermal injury. Thus, this study
      showed the involvement of the TRPA1 receptor in the nociception and inflammation
      caused by thermal injury and suggested that TRPA1 antagonists might be useful as
      novel treatments for pain and inflammation by topical application.

PMID- 30236551
TI  - The effect of DSPE-PEG2000, cholesterol and drug incorporated in bilayer on the
      formation of discoidal micelles.
AB  - In cholesterol/DSPE-PEG2000/DPPC systems, nano-disks could evolve between
      liposomes and spherical micelles in a certain range of PEG-lipids. How
      cholesterol or drug influences this evolution and what about the properties of
      discoidal micelles as drug carrier are still not clear. Aiming at this,
      nanocarriers with different contents of cholesterol and DSPE-PEG2000 were
      prepared by thin-film-hydration method. Firstly, the bilayer fluidity of
      nanocarriers was investigated and proved to decrease with the increase of
      cholesterol, and the cooperative degree between phospholipids was also related to
      cholesterol content in an order of 30 > 40 > 15 > 0 mol%. Then three different
      levels of cholesterol were chosen to study its effect on DSPE-PEG2000 limit used
      to form discoidal micelles. For transition from liposomes to disks, the limit of
      DSPE-PEG2000 employed is above 0.5 mol% at 0 mol% cholesterol, above 15 mol% at
      30 mol% cholesterol and above 5 mol% at 40 mol% cholesterol observed from TEM
      images, indicating that nanocarriers with 30 mol% cholesterol formed discoidal
      micelles most difficultly due to the strongest interaction between phospholipids.
      However, membrane fluidity seems to have little responsibility for the different
      morphologies. And imatinib (IM) could promote the formation of discoidal
      micelles, resulting from the interaction between IM and polar headgroups of
      phospholipid demonstrated by DSC. The relative reduction of entrapment efficiency
      for three agents with different dissolving properties showed that lipophilic
      drugs were the most suitable drug that could be loaded into discoidal micelles.
      In addition, the discoidal micelle formulations tested could readily change to
      other morphologies after 80 days' storage. In conclusion, both the cholesterol
      content and IM could affect the formation of discoidal micelles by probably
      influencing the interaction between phospholipids, also the discoidal structure
      was not stable enough and only suitable for lipophilic drug loading. We hope this
      study could help to design the formula and choose the proper drugs that may
      retain the discoidal morphology.

PMID- 30236552
TI  - Design of in vitro skin permeation studies according to the EMA guideline on
      quality of transdermal patches.
AB  - Transdermal patches and medicated plasters are designed to sustain efficacious
      systemic or loco-regional drug concentrations, respectively. In both cases, drug
      skin permeation is a critical attribute from the early stage of the
      pharmaceutical development. In 2014, the EMA introduced the "Guideline on the
      quality of transdermal patches", in which the importance of equivalence of drug
      fluxes in in vitro skin permeation study was particularly emphasized to generic
      or abridged applications for the marketing authorization or manage dossier
      variations during the product cycle life. Moving from experimental data, this
      work provides information on the set-up of such studies and the statistical
      evaluation of obtained fluxes. In particular, the impact of the inter-sample
      variability on the equivalence assessment was deeply investigated by using
      formulation pairs containing propranolol, diclofenac or nitroglycerine. The main
      outputs of the work were attributable to the definition of the acceptability
      interval and number of replicates to be performed. As an example, the equivalence
      of two propranolol patches (flux variability lower than 25%) can be assessed
      using six replicas and a confidence limit within the 0.8-1.25 range (alpha =
      0.05; power 90%). In contrast, the equivalence of diclofenac plasters, which
      exhibit a variability near the 50%, can be demonstrated increasing the number of
      replicas (i.e., 20 skin samples) for each formulation and widening the acceptance
      range according to the statistical approach proposed in the work.

PMID- 30236553
TI  - Usefulness of urinary parameters in advanced chronic kidney disease.
AB  - : This review discusses the diagnostic value of urinary parameters in the setting
      of advanced chronic kidney disease and we present the key concepts that summarise
      the suggestions of the manuscript. URINARY VOLUME: The amount of fluid intake may
      be a non-established risk factor for CKD. For these patients, a urinary output
      >=2-3 l/day is a reasonable proposal. This recommendation is not applicable to
      patients with cardiorenal syndrome or fluid overload risk. NA: This determination
      is very useful to monitor salt intake. Reducing urinary Na<120 mEq/day (?salt
      intake<=5-6g) is a reasonable objective. URINARY UREA NITROGEN (UUN): This
      parameter is useful to estimate protein intake (Maroni BJ equation). A protein
      intake between 48-72g (0.8-0.9g/kg/day according to weight) is equivalent to UUN
      7-10g/day approximately. ACID LOAD AND POTASSIUM: Acid load reduction may be an
      additional strategy in the nutritional management of this population. It may be
      estimated indirectly from a diet survey or by measuring the elimination of UUN
      and Kur. The limits of this recommendation have not been established, but we
      propose a cautious and prudent diet of fruit and vegetables. PHOSPHORUS: There is
      a significant positive correlation between phosphorus and protein, both in
      dietary records and urine elimination. Based on this information, we suggest a
      urinary P excretion<800mg/day or<600mg/day for patients with GFR<25ml/min
      or<15ml/min, respectively. CONCLUSION: Urinary parameters provide sensitive and
      useful knowledge for clinical practice, provide information about the dietary
      habits of patients and the adherence to our recommendations.

PMID- 30236555
TI  - Is It Acute Pancreatitis or Recurrent Acute Pancreatitis Leading to Chronic
      Pancreatitis that Increases Pancreatic Cancer Risk?

PMID- 30236554
TI  - TNF-alpha suppresses osteogenic differentiation of MSCs by accelerating P2Y2
      receptor in estrogen-deficiency induced osteoporosis.
AB  - Tumor Necrosis Factor-alpha (TNF-alpha)-inhibited osteogenic differentiation of
      mesenchymal stem cells (MSCs) contributes to impaired bone formation, which plays
      a central role in the pathogenesis of postmenopausal osteoporosis. However, the
      exact mechanisms of TNF-alpha-inhibited osteoblast differentiation have not been
      fully elucidated. Multiple P2 purinoceptor subtypes are expressed in several
      species of osteoblasts and are confirmed to regulate bone metabolism. The purpose
      of this study is to investigate whether P2 purinoceptors are involved in TNF
      alpha-inhibited osteoblast differentiation. This study shows TNF-alpha increased
      P2Y2 receptor expression in the differentiation of MSCs into osteoblasts in a
      noticeable manner. Overexpressing or silencing of the P2Y2 receptor either
      impaired or promoted osteogenic differentiation of MSCs significantly. Silencing
      of the P2Y2 receptor attenuated the inhibitory effects of TNF-alpha on
      osteoblastic differentiation of MSCs. In addition, silencing of the P2Y2 receptor
      evidently alleviated TNF-alpha-inhibited MSC proliferation. P2Y2 receptor
      expression was mechanistically upregulated by TNF-alpha mainly through
      extracellular regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK)
      signaling pathways. Overall, our results revealed a novel function of the P2Y2
      receptor and suggested suppressing the P2Y2 receptor may be an effective strategy
      to promote bone formation in estrogen deficiency-induced osteoporosis.

PMID- 30236556
TI  - Reply.

PMID- 30236557
TI  - Reply.

PMID- 30236558
TI  - Reply.

PMID- 30236559
TI  - Reply.

PMID- 30236560
TI  - Reply.

PMID- 30236561
TI  - Considering Nursing Issues as You Vote.

PMID- 30236562
TI  - Multimodal Perioperative Analgesia Regimen: All Clear?

PMID- 30236563
TI  - Reply.

PMID- 30236564
TI  - Malignant Hyperthermia: A Review.
AB  - Malignant hyperthermia is an uncommon, but potentially lethal condition that may
      be encountered during the perioperative period. There is wide variability in the
      manner in which malignant hyperthermia may manifest. For a patient to survive a
      malignant hyperthermia crisis, prompt recognition and treatment is of paramount
      importance. Perioperative nurses play a pivotal role in the successful management
      of malignant hyperthermia. The fictitious case study presented in this paper
      describes the identification, presentation, pathophysiology, and treatment of a
      general anesthesia patient with fulminant malignant hyperthermia.

PMID- 30236565
TI  - Evidence Based Use of Cuffed Endotracheal Tubes in Children.
AB  - Historically, the use of cuffed endotracheal tubes (ETTs) was reserved for
      children aged 8 years or older to minimize the risks of postextubation laryngeal
      edema. However, since publication of a 1997 study, researchers have consistently
      presented evidence that appropriately used cuffed ETTs are as safe as uncuffed
      ETTs. Because of the advantages of cuffed ETTs in the perianesthesia setting, the
      transition to cuffed ETTs in children is now complete. However, risks related to
      using cuffed ETTs in young children increase when guidelines for safe and
      appropriate use are not followed. Perianesthesia practitioners caring for
      children must understand the implications related to ETT type, correct ETT
      sizing, and the monitoring and control of ETT cuff pressure. The purpose of this
      educational module is to present evidence-based guidelines for the appropriate
      use of cuffed ETTs in children less than 8 years of age in the perianesthesia
      setting.

PMID- 30236566
TI  - Preventing Opioid-Induced Respiratory Depression in the Hospitalized Patient With
      Obstructive Sleep Apnea.
AB  - PURPOSE: To enhance the role of nursing interventions in the management of
      perioperative opioid-induced respiratory depression (OIRD) in patients with
      obstructive sleep apnea (OSA). DESIGN: Narrative review of the literature.
      METHODS: Literature reviewed with emphasis on recommendations by professional and
      accrediting organizations. FINDINGS: Postsurgical OIRD increases hospital stay
      (55%), cost of care (47%), 30-day readmission (36%), and inpatient mortality (3.4
      fold). OSA increases the risk of OIRD and may result in legal claims averaging
      $2.5 million per legal claim. CONCLUSIONS: Nursing interventions are essential to
      improving outcome and reduce cost in the management of postsurgical OIRD in OSA
      patients.

PMID- 30236567
TI  - Military Service Members and Emergence Delirium Screening: An Evidence-Based
      Practice Project.
AB  - PURPOSE: Emergence delirium (ED) is a postoperative phenomenon characterized by
      agitation, confusion, and violent physical or verbal behavior that can occur
      after general anesthesia. Preoperative identification of patients at risk for ED
      may allow providers to take steps to minimize the incidence or severity of ED.
      Because no formal tool currently exists, the purpose of this project was to
      develop and evaluate a screening tool based on available evidence of ED risk
      factors. DESIGN: This quality improvement project used a preimplementation and
      postimplementation design. METHODS: One hundred consecutive adult patient charts
      were reviewed 2 months before implementation of the project questionnaire. These
      data were used to confirm preimplementation screening rates. Postimplementation,
      prospective data were gathered to test this newly developed assessment tool for
      usefulness in the clinical setting. FINDINGS: The use of this focused screening
      tool significantly increased preoperative identification of patients at risk for
      ED compared with the preimplementation preoperative screening routine.
      Identification rates for at-risk patients rose from 5% to 21%-22.5% using this
      tool. CONCLUSIONS: This project demonstrated that the use of a focused tool to
      identify risk factors for ED could significantly increase actual identification
      rates for at-risk patients in the clinical setting.

PMID- 30236568
TI  - A Clinical Trial of the Effect of Warm Intravenous Fluids on Core Temperature and
      Shivering in Patients Undergoing Abdominal Surgery.
AB  - PURPOSE: This study was conducted to investigate the effect of warm intravenous
      fluids on shivering and core temperature of patients undergoing abdominal
      surgery. DESIGN: This study was a two-group clinical-control trial. METHODS:
      Ringer's solution at normal room temperature and serum at 38 degrees C were
      infused in the control and intervention groups, respectively. Shivering, core
      temperature, SpO2, and vital signs were measured at admission to the operating
      room and postanesthesia care unit (PACU) and 30 minutes after the admission to
      the PACU. FINDINGS: There was a significant difference between the two groups in
      terms of shivering, core temperature, and pulse rate at the time of admission to
      the PACU and 30 minutes after. CONCLUSIONS: Ringer's solution at 38 degrees C
      instead of room temperature can be used to reduce the incidence of postanesthetic
      hypothermia and shivering in patients undergoing abdominal surgery. Using this
      method in addition to other nursing care is recommended preoperatively.

PMID- 30236569
TI  - Early Rehydration in Surgical Patients With Prolonged Fasting Decreases
      Postoperative Nausea and Vomiting.
AB  - PURPOSE: The purpose of the project was to reduce the incidence of postoperative
      nausea and vomiting (PONV) in adult surgical patients who fasted for more than 12
      hours with the administration of a preinduction intravenous fluid (IVF) bolus.
      DESIGN: This interdisciplinary project used the Plan-Do-Study-Act model for
      quality improvement. METHODS: After institutional approval, 381 consecutive adult
      surgical patients were evaluated for participation; 148 patients fasted more than
      12 hours and met inclusion criteria to receive a 1 liter, IV fluid bolus before
      anesthesia induction. All patients received general inhalational anesthesia and
      prophylactic doses of dexamethasone and ondansetron, along with peripheral nerve
      blocks appropriate for surgical case type. FINDINGS: Only 96 (64%) qualified
      patients received the complete bolus before anesthesia induction. In this group,
      the incidence of PONV was 4.25%. CONCLUSION: The use of a simple rehydration
      protocol reduced the incidence of PONV in patients with prolonged fasting times.
      Time and personnel constraints were identified as barriers that prevented full
      compliance with the protocol.

PMID- 30236570
TI  - Incidence, Course, and Characteristics of Hydralazine-Associated Tachycardia
      During Phase I Postanesthesia Recovery.
AB  - PURPOSE: This study aims to characterize the development of tachycardia after
      intravenous hydralazine administration during Phase I recovery. DESIGN:
      Retrospective observational study design. METHODS: The medical records of 745
      adult surgical patients who were administered hydralazine during Phase I recovery
      between January 1, 2010 and December 31, 2014 were electronically reviewed to
      characterize episodes of tachycardia. FINDINGS: Seventy patients (94.0 cases per
      1,000 administrations; 95% confidence interval = 74.0 to 117.2) developed
      tachycardia with a median increase of 23 beats per minute (bpm; interquartile
      range [IQR] = 15 to 37), a maximum rate of 106 bpm (IQR = 103 to 111; range = 101
      to 131), and duration of 28 minutes (IQR = 5 to 86). The median onset of
      tachycardia was 43 minutes (IQR = 20 to 93), with 40% occurring after the first
      hour. Tachycardia was associated with female sex (P < .001), younger age (P <
      .001), and those with lesser comorbidities (P < .009). CONCLUSIONS: A sizeable
      proportion of cases of tachycardia associated with hydralazine administration
      occurred after 1 hour, suggesting that these patients who may not tolerate a
      faster heart rate warrant longer duration of monitoring.

PMID- 30236571
TI  - Effectiveness of Lifestyle Modification Education on Knowledge, Anxiety, and
      Postoperative Problems of Patients With Benign Perianal Diseases.
AB  - PURPOSE: The aim of this study was to evaluate the effectiveness of preoperative
      planned education about lifestyle modifications on knowledge, anxiety level, and
      postoperative problems of the patients with benign perianal disease. DESIGN: The
      study was a quasi-experimental design. METHODS: The sample was a total of 102
      patients undergoing surgical procedure for hemorrhoid and fissure in the general
      surgery unit of a state hospital in Turkey. Data were collected using the
      Descriptive Characteristics Determination Questionnaire, the Knowledge
      Determination Questionnaire, the Postoperative Problems Determination
      Questionnaire, and the State and Trait Anxiety Inventory. FINDINGS: Preoperative
      written and verbal planned education about lifestyle modifications improved
      knowledge and decreased anxiety levels of the patients. There were no
      statistically significant differences between the control and study groups in
      postoperative problems other than leakage. CONCLUSIONS: Results of the present
      study showed that nurse-conducted education on lifestyle modification of
      hemorrhoid and fissure was effective.

PMID- 30236572
TI  - Effectiveness of Preoperative Visitation on Postanesthesia Complications.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of preoperative
      visitation on postanesthesia complications after hernia surgery. DESIGN: In this
      quasi-experimental study, 70 patients receiving elective hernia surgery were
      purposefully selected. METHODS: In the evening preceding surgery, the surgical
      technologist visited the patient in the surgical ward. Data were collected by
      checklist of vital signs and postanesthesia complications. FINDINGS: A greater
      increase is observed in the systolic blood pressure of the experimental group at
      the moment of entering the postanesthesia care unit. A significant difference was
      found between groups in the intensity of postanesthesia agitation in the
      postanesthesia care unit patients, with a higher incidence among the experimental
      group. CONCLUSIONS: According to the findings, preoperative education programs
      for operating room staff and other behavioral and mental interventions to manage
      surgery and its consequences in elective surgical patients is recommended.

PMID- 30236573
TI  - Presurgery Anxiety and Day Surgery Patients' Need for Information.
AB  - PURPOSE: This study was done to determine day surgery patients' presurgery
      anxiety levels related to information received. DESIGN: A descriptive and cross
      sectional model was used. METHODS: The study was conducted with 151 patients who
      underwent day surgery at surgical clinics of a university hospital in Turkey. The
      data were gathered with the Patient Information Form and the State-Trait Anxiety
      Inventory. FINDINGS: The findings were that most of the patients received
      information about their day surgery, but the rate of receiving information about
      some issues was very low. Most of the patients reported that although they did
      not have any anxiety about surgery and anesthesia, observations revealed that
      their average state and trait anxiety scores were high. CONCLUSIONS: Study
      results can be used as a basis to provide patients with clarifications about
      surgeries during the presurgery period and as a means of decreasing their anxiety
      about surgery and anesthesia.

PMID- 30236574
TI  - Family Visitation in the Postanesthesia Care Unit: Implementation of a Nurse
      Liaison Role.
AB  - The purpose of this article was to report on the nurse liaison role developed at
      a 400-bed community hospital in response to a previously published best practice
      project on the effect of family visitation in the PACU on family member anxiety.
      The evidence resulted in the development of the nurse liaison role, which changed
      nursing practice and involved each area of perioperative services as we embarked
      on family-centered care (FCC). The nurse liaison program has served as a model
      for other hospital departments as well as area hospitals. Guidelines for
      implementation of the program, which included FCC, are discussed as well as job
      guidelines, job descriptions, challenges, and outcomes.

PMID- 30236575
TI  - Nonclinical Factors Affecting PACU Discharge: A Clinical Audit in a One-Day
      Surgery Unit.
AB  - PURPOSE: To determine the nonclinical causes of delayed discharge from the
      postanesthesia care unit (PACU). DESIGN: A prospective observational study.
      METHODS: Over a 2-month period, data were collected on 576 patients who were
      transferred to the clinical areas from PACU after surgery. Patients were
      considered ready for discharge after they had achieved a satisfactory discharge
      score. FINDINGS: The most common documented reason for nonclinical delayed
      discharge was lack of available transport (45.5%; n = 310) followed by bed
      availability (13%; n = 89) and the receiving registered nurse's readiness to
      accept a transfer from PACU (7.3%; n = 50). CONCLUSIONS: Nonclinical delays
      account for a considerable extension of a patient's time in PACU. The findings of
      this study suggest that understanding and addressing the causes of delayed
      discharge in PACU may help to improve patient flow and reduce discharge times.
      Future research should include the cost associated with these delays and assess
      the effectiveness of interventions introduced to eliminate such delays.

PMID- 30236576
TI  - Patients' Perceptions of Short-Term Recovery After a Gastric Bypass.
AB  - PURPOSE: To explore gastric bypass patients' perceptions of their postoperative
      recovery over 1 month. DESIGN: A standardized questionnaire, the postoperative
      recovery profile, was used. METHODS: Postoperative recovery profile is a multi
      item questionnaire for self-assessment of general postoperative recovery.
      Participants were patients who had undergone gastric bypass surgery (n = 39). The
      changes in recovery between 1 day and 1 month postsurgery were evaluated by a
      statistical method developed specifically for analyzing changes in paired ordered
      data over time. FINDINGS: Most of the symptoms and/or functions were
      significantly improved on a group level. The most marked improvement was to pain
      and sleeping difficulties followed by mobilization. In terms of the psychological
      items, the proportion of patients who indicated no problems was high at both
      endpoints. The items that deviated from the improvement pattern were appetite
      changes and gastrointestinal function which demonstrated a relatively high
      proportion of deterioration, and the individual variability was prominent.
      CONCLUSIONS: There is a need for interventions to improve recovery on a group as
      well as an individual level.

PMID- 30236577
TI  - Effects of Tactile Desensitization on Postoperative Pain After Amputation
      Surgery.
AB  - PURPOSE: Pain in the acute setting after amputation is complex with multiple
      types of pain experienced, including somatic and neuropathic. No studies have
      measured multiple pain control modalities while using self-management techniques
      for acute amputation pain. Desensitization could provide a means of pain control
      for somatic and neuropathic pain. The purpose of this study was to test the
      efficacious use and effects of tactile desensitization in managing acute
      postoperative pain after lower limb amputation. DESIGN: This was a pre
      experimental repeated measure study. METHODS: Pain description, intensity,
      anxiety, depression, and medication usage were measured during repeated time
      periods. Pain intensity was measured before and after each intervention along
      with efficacy. FINDINGS: Of the times the intervention was self-administered (n =
      50) there was a statistically significant reduction in the pain level (P < .001)
      with large effect sizes for all paired comparisons. Participants found the
      intervention efficacious and feasible to use. CONCLUSIONS: The findings support a
      reduction in pain intensity scores using pain medication coupled with tactile
      desensitization.

PMID- 30236578
TI  - Validation of the Turkish Version of the Surgical Fear Questionnaire.
AB  - PURPOSE: Preoperative surgical fear is an emotional reaction that can be observed
      in many patients who are waiting to undergo a surgical procedure. The Surgical
      Fear Questionnaire (SFQ) was originally developed to determine the level of fear
      in patients who are to undergo surgery; this study aims to translate the
      questionnaire into the Turkish language and to test the validity and reliability
      of this Turkish version. DESIGN: Methodological research model. METHODS: The
      population of this methodological study included the patients who presented to
      surgical clinics at a university hospital in Turkey between January and August
      2016 and were scheduled to undergo elective surgery; the sample involved 405
      patients who met the inclusion criteria. FINDINGS: Results of the analyses showed
      that the SFQ can be used with two subscales-the S subscale, which shows the short
      term consequences, and the L subscale, which shows the long-term consequences of
      surgery. The mean score of the patients was 18.03 +/- 11.44 on the former, 19.52
      +/- 11.87 on the latter, and 37.55 +/- 21.11 for the entire questionnaire. The
      Cronbach's alpha coefficient was 0.96 for the SFQ-S subscale, 0.90 for the SFQ-L
      subscale, and 0.93 for the entire questionnaire. CONCLUSIONS: In this study, the
      translated SFQ was found to have a similar structure to the original
      questionnaire and a high level of validity and reliability and therefore can be
      used in Turkey.

PMID- 30236579
TI  - Nurses' Knowledge and Barriers Regarding Pain Management.
AB  - PURPOSE: The purpose of this study was to identify Polish nurses' experiences and
      perceptions about the barriers to postoperative pain management in older adults.
      DESIGN: The study was conducted using a dedicated questionnaire. METHODS: Eleven
      hospitals participated in this study. The project involved 1,602 nurses working
      on surgical hospital wards. A descriptive exploratory survey and a qualitative
      content analysis were used. FINDINGS: Access to journals on evidence-based
      practice related to pain assessment and management in elderly patients was
      assessed as less important by the respondents. Knowledge drawn from the media and
      scientific and medical journals was assessed by the respondents as
      unsatisfactory. The greatest barrier to nurses was that scientific articles are
      published in English. CONCLUSIONS: Nurses' awareness of evidence-based practice
      increases with their education. Among the key problems is the lack of available
      professional publications in the Polish literature, ignorance of English,
      shortage of time, and lack of support from chief physicians of the ward.

PMID- 30236580
TI  - Sugammadex Rescue in Avoiding Intensive Care Unit Admission in an Octogenarian
      Undergoing Emergency Laparotomy.
AB  - Postlaparotomy management for elderly patients with underlying comorbidities is
      always a challenge because of poor cardiorespiratory reserves and prolonged
      effect of anesthetic drugs. For these reasons, such patients usually require
      intensive care unit (ICU) admission in the postoperative period. We report a case
      of an 85-year-old chronic smoker with controlled diabetes mellitus who needed an
      emergency laparotomy for a perforated gastric ulcer. Unfortunately, there was a
      shortage of ICU backup. With the successful conduct of an early surgery using
      combined general and regional anesthesia, the use of sugammadex (Bridion, Merck
      Sharp & Dohme Corp, Oss, the Netherlands) as a reversal agent, a skilled surgeon,
      and good postanesthesia care, the patient did not require ICU admission. He
      recovered fast and was discharged home 4 days after surgery. This case study aims
      to contribute to the literature on experience of a successful conduct of
      anesthesia in a high-risk geriatric patient when ICU facilities are limited.

PMID- 30236581
TI  - Postoperative Cognitive Dysfunction in the Elderly: A Review Comparing the
      Effects of Desflurane and Sevflurane.
AB  - PURPOSE: The incidence of postoperative cognitive dysfunction (POCD) remains a
      relatively common complication in the elderly following surgery. Use of
      anesthesia for surgery might precipitate certain cognitive alterations. The
      purpose of this review is to address the impact of two volatile anesthetic
      agents, desflurane and sevoflurane, on POCD. DESIGN: The focus of this review was
      on postoperative recovery and complications using two anesthetic agents. METHODS:
      Several databases including PubMed and Cochrane were searched from the date of
      inception. The search words POCD, elderly, general anesthetics, desflurane, and
      sevoflurane were used and the search was limited to human, randomized clinical
      trials, and English. FINDINGS: The findings show no difference in the emergence
      time between sevoflurane and desflurane and the incidence of POCD. CONCLUSIONS:
      No definitive conclusion can be drawn about the type of anesthetic used and its
      relation to occurrence of POCD. However, the information presented is crucial,
      which can help to improve anesthetic usage and patient safety.

PMID- 30236582
TI  - The Relationship Between Patient-Controlled Analgesia and Postcesarean Section
      Pressure Ulcers: Analysis of Medical Record Data.
AB  - PURPOSE: In this study, we aim to investigate the relationship between patient
      controlled analgesia (PCA) and the incidence of pressure ulcer in postcesarean
      section mothers. DESIGN: A retrospective analysis was performed among consecutive
      cesarean section mothers in 2016. METHODS: Univariate and multivariate logistic
      regression was used to analyze the relationship between PCA and postcesarean
      section pressure ulcers. FINDINGS: One thousand nine hundred eighteen cesarean
      section mothers were included in the study. Forty-five mothers (2.3%; 95%
      confidence interval [CI], 1.7%-3.1%) developed stage I pressure ulcer. The
      pressure ulcers were cured in 2 to 5 days. Eighty percent (1,535) of mothers
      received PCA after cesarean section surgery. Pressure ulcer incidence was
      significantly higher in the PCA group compared with non-PCA groups (2.9% vs 0.0%,
      Fisher's exact P < .0001). Patient-controlled intravenous analgesia and patient
      controlled epidural analgesia showed the same pressure ulcer risk (3.2% vs 2.6%,
      chi2 = 0.581, P = .446). After multivariate analysis by logistic regression, the
      adjusted odds ratio of PCA for pressure ulcer risk was 33.632, with a 95% CI of
      25.061 to 45.134. CONCLUSIONS: Our results showed PCA was an independent risk
      factor for pressure ulcer in postcesarean section mothers. Although the pressure
      ulcers were all rated as stage I and can be cured in 2 to 5 days, we still
      recommended some pressure ulcer prevention strategy should be used for these
      mothers.

PMID- 30236583
TI  - Why Do Nurses Work Where They Work?

PMID- 30236584
TI  - Erratum.

PMID- 30236585
TI  - The Gathering of Nations: From Copenhagen to Sydney!

PMID- 30236586
TI  - Machine Learning in Health Care.

PMID- 30236588
TI  - Safety and Feasibility.

PMID- 30236589
TI  - Perseverance and Persistence: The FIDO Philosophy.

PMID- 30236590
TI  - Gravitational torque partially accounts for proprioceptive acuity.
AB  - Proprioception of the upper extremity is commonly measured using joint position
      sense tasks. Recent evidence suggests heightened position sense at elevation
      angles in the shoulder and elbow near 90 degrees  in the sagittal plane. The
      influence of external torque has been suggested to play a pivotal role in the
      heightened acuity in elevated positions due to increased moment arm with respect
      to gravitational vectors. We hypothesized that the addition of a buoyance vector
      in opposition to this gravitational vector would reduce the influence of torque
      on proprioceptive acuity, resulting in consistent position sense errors with
      respect to elevation angle. Joint position sense was measured using an apple iPod
      touch using a custom application. Participants elevated their arm to 50, 70 and
      90 degrees  of elevation in the sagittal plane in the absence of visual feedback.
      Data were collected in three conditions, normal (control) and submerged and
      weighted. We found angular differences between control and submerged conditions,
      but not between control and weighted conditions. When the arm was elevated to 90
      degrees  in the submerged condition, we found participants undershot the target
      position by approximately -0.5 degrees  with the addition of the buoyancy force
      vector. Participants without this buoyancy vector at the same target position
      consistently overshot the target by approximately 2.0 degrees , which suggests
      that external torque may be more involved in the direction of proprioceptive
      errors more than the magnitude of the error as the magnitude of the difference
      was relatively small (2.5 degrees ).

PMID- 30236587
TI  - Can Multidimensional Pain Assessment Tools Help Improve Pain Outcomes in the
      Perianesthesia Setting?

PMID- 30236591
TI  - Is the association between sociodemographic variables and physical activity
      levels in adolescents mediated by social support and self-efficacy?
AB  - OBJECTIVE: Analyze whether the association between sociodemographic variables and
      physical activity levels is mediated by psychosocial factors. METHODS: This is a
      cross-sectional epidemiological study of public and private high school students
      in Joao Pessoa, Paraiba state, Brazil. A total of 2540 adolescents (57.0% female)
      were analyzed (16.4+/-1.2 years). Physical activity was estimated using a
      questionnaire, self-efficacy, and parents' and friends' social support by scales,
      all previously validated. RESULTS: The association between sex and the physical
      activity level of adolescents was partially mediated by the social support of
      parents (beta=0.79; p<0.001) and friends (beta=2.96; p<0.001), and the
      association between age and physical activity level was partially mediated by
      parents' social support (beta=0.78; p<0.001). The associations between sex and
      age and physical activity levels of adolescents were mediated by the social
      support of parents and friends. CONCLUSIONS: Differences in physical activity
      levels between adolescent females and males and between younger and older
      adolescents may be partially explained by differences in social support provided
      by parents and friends. Implementation strategies to increase the social support
      of parents and friends may help reduce the differences in physical activity
      levels between these subgroups of adolescents.

PMID- 30236592
TI  - Parent SNAP-IV rating of attention-deficit/hyperactivity disorder: accuracy in a
      clinical sample of ADHD, validity, and reliability in a Brazilian sample.
AB  - OBJECTIVE: To investigate the psychometric properties of the short or multimodal
      treatment study version of the Swanson, Nolan, and Pelham, Version IV (SNAP-IV)
      scale, which measures attention-deficit/hyperactivity disorder and oppositional
      defiant disorder symptoms. METHODS: Participants were 765 parents of children
      from 4 to 16 years old (641 non-attention-deficit/hyperactivity disorder and 124
      attention-deficit/hyperactivity disorder children) from Belo Horizonte, Brazil,
      who reported sociodemographic characteristics and answered the SNAP-IV. Parents
      of the clinical sample also underwent the K-SADS-PL interview. RESULTS: Age was
      significantly associated with SNAP-IV hyperactivity-impulsivity problems (r=
      0.14), but not with inattention or oppositional defiant disorder. Sex was a
      significant influence on attention-deficit/hyperactivity disorder and
      oppositional defiant disorder severity (all p<0.001), with boys showing higher
      scores in the full sample, but not within the attention-deficit/hyperactivity
      disorder group. Exploratory and confirmatory factor analysis supports a three
      factor structure of the SNAP-IV scale. Moderate-to-strong correlations were found
      between SNAP-IV and K-SADS-PL measures. All SNAP-IV scales showed very high
      internal consistency coefficients (all above 0.91). SNAP-IV inattention scores
      were the most predictive of attention-deficit/hyperactivity disorder diagnosis
      (AUC: 0.877 for the averaging rating method and the raw sum method, and 0.874 for
      the symptom presence/absence method). CONCLUSION: The parent SNAP-IV showed good
      psychometric properties in a Brazilian school and clinical sample.

PMID- 30236593
TI  - Ultra-low-dose chest computed tomography without anesthesia in the assessment of
      pediatric pulmonary diseases.
AB  - OBJECTIVE: To evaluate the feasibility of using ultra-low-dose computed
      tomography of the chest with iterative reconstruction without anesthesia for
      assessment of pulmonary diseases in children. METHODS: This prospective study
      enrolled 86 consecutive pediatric patients (ranging from 1 month to 18 years)
      that underwent ultra-low-dose computed tomography due to suspicion of pulmonary
      diseases, without anesthesia and contrast. Parameters used were: 80kVp; 15-30mA;
      acquisition time, 0.5s; and pitch, 1.375. The adaptive statistical iterative
      reconstruction technique was used. Subjective visual evaluation and quantitative
      assessment of image quality were done using a 5-point scale in 12 different
      structures of the chest. RESULTS: Mean age was 66 months (interquartile range, 16
      147). Final diagnosis was performed in all exams, and 44 (51.2%) were diagnosed
      with cystic fibrosis, 27 (31.4%) with bronchiolitis obliterans, and 15 (17.4%)
      with congenital pulmonary airways malformations. Diagnostic quality was achieved
      in 98.9%, of which 82.6% were considered excellent and 16.3% were slightly
      blurred but did not interfere with image evaluation. Only one case (1.2%)
      presented moderate blurring that slightly compromised the image, and previous
      examinations demonstrated findings compatible with bronchiolitis obliterans. Mean
      effective radiation dose was 0.39+/-0.15mSv. Percentages of images with motion
      artifacts were 0.3% for cystic fibrosis, 1.3% for bronchiolitis obliterans, and
      1.1% for congenital pulmonary airways malformations. CONCLUSION: Chest ultra-low
      dose computed tomography without sedation or anesthesia delivering a sub
      millisievert dose can provide image quality to allow identification of common
      pulmonary anatomy and diseases.

PMID- 30236594
TI  - The impact of legislation mandating breast density notification - Review of the
      evidence.
AB  - Breast density (BD) is an independent risk factor for breast cancer and reduces
      the sensitivity of mammography. The enactment of BD legislation in a majority of
      states in the USA mandating notification of risks associated with BD directly to
      women undergoing mammography has catapulted interest in BD among women,
      physicians, and policymakers. We therefore report a descriptive review of the
      evidence on the impact of enactment of BD legislation. Based on 22 eligible
      studies, we identified four broad themes of research: studies of the impact on
      screening rates, most showing increased utilisation of supplemental screening;
      studies exploring the effect on women, radiologists, or primary physicians
      (reporting heterogeneous effects on knowledge, awareness, perceptions, attitudes
      and behaviour; and changes in practice); few studies assessing the population
      impact (effect on screening outcomes or breast cancer stage); and studies of
      costs highlighting the economic burden from supplemental screening. Given that
      many of the studies were retrospective single institution studies (comparing pre-
      and post-legislation) or small surveys with a paucity of population-level
      studies, we highlight areas meriting additional research. The information
      described in this review can inform research priorities where BD legislation has
      been introduced and can be used to guide world-wide policy or practice decisions
      where BD legislation may be under debate or contemplation.

PMID- 30236595
TI  - JAK2, PD-L1, and PD-L2 (9p24.1) Amplification in Metastatic Mucosal and Cutaneous
      Melanomas with Durable Response to Immunotherapy.
AB  - As immune checkpoint inhibitors are rapidly developing into the standard of care
      for patients with advanced melanoma, the value of diagnostic metrics to predict
      response to immunotherapy is steadily increasing. Next-generation sequencing
      based parameters include tumor mutation burden (TMB) as well as genomic
      amplification of PD-L1/PD-L2/JAK2 at 9p24.1. At present, there are limited
      studies documenting response to checkpoint blockade in 9p24.1 amplified solid
      tumors. Herein, we have compared a cutaneous melanoma with a mucosal melanoma,
      both with 9p24.1 amplifications and durable response to immunotherapy. While the
      cutaneous melanoma had a high TMB, the mucosal melanoma had a lower TMB compared
      to the mean TMB for all melanomas within the institutional clinical sequencing
      cohort. In summary, PD-L1/PD-L2/JAK2 amplification was associated with durable
      response to therapy for both cases and this genomic signature is a potential
      valuable metric in predicting response to immunotherapy.

PMID- 30236596
TI  - High expression of SLC17A9 correlates with poor prognosis in colorectal cancer.
AB  - Solute carrier family 17 member 9 (SLC17A9) is a member of the family of
      transmembrane proteins that are involved in the transport of small molecules. The
      role of SLC17A9 in colorectal cancer (CRC) remains poorly understood. The present
      study aimed to demonstrate the clinicopathological significance and prognostic
      role of SLC17A9 in CRC. Here, we firstly analyzed the data from The Cancer Genome
      Atlas (TCGA) on SLC17A9 expression in colorectal cancer datasets and detected
      SLC17A9 expression level in 8 pairs of fresh CRC tissues and adjacent non
      tumorous tissues by quantitative real-time reverse transcription polymerase chain
      reaction (qRT-PCR) and western blotting assays. Immunohistochemical staining was
      used to detect SLC17A9 protein expression in 144 CRC patients in our center. The
      bioinformatic analysis, western blotting and immunohistochemical analyses
      revealed that SLC17A9 was significantly upregulated in CRC specimens compared
      with adjacent non-tumorous tissues. SLC17A9 overexpression was significantly
      correlated with several clinicopathological features, such as advanced T stage
      (p<0.001), N stage (p<0.001), M stage (p<0.001), TNM stage (p<0.001), and tumor
      location (p=0.01). A Kaplan-Meier survival curve suggested that higher SLC17A9
      expression was statistically correlated with poor overall survival (OS) and
      disease free survival in patients with CRC. Univariate and multivariate Cox
      regression analyses demonstrated that SLC17A9 was an independent prognostic
      predictor for survival of CRC patients. Therefore, our data suggested that
      SLC17A9 may play an important role in the progression of CRC and may potentially
      be used as an independent biomarker for prognostic evaluation of CRC.

PMID- 30236597
TI  - Stressnology: The primitive (and problematic) study of life stress exposure and
      pressing need for better measurement.
AB  - Life stress is central to many contemporary theories of human health and
      behavior. Despite this fact, numerous conceptual and measurement issues remain
      unresolved. The present article explores these topics by first summarizing
      several key definitional and conceptual matters that are important for life
      stress research. Second, I introduce stressnology, defined herein as the
      fictitiously named, but otherwise very real and problematic approach to studying
      life stress exposure that involves measuring only the superficial contours of
      this very complex construct. Finally, I review some recent methodological
      advancements that have the potential to move us past primitive approaches to
      conceptualizing and assessing life stress. Ultimately, although the influence
      that life stress has on human health and behavior is profound, our understanding
      of this construct-and how it affects wellbeing, functioning, and development-is
      still very limited. Using state-of-the-art instruments for assessing life stress
      exposure, especially across the entire life course, should therefore be a top
      scientific and clinical priority.

PMID- 30236598
TI  - Effects of auriculasin on vascular endothelial growth factor (VEGF)-induced
      angiogenesis via regulation of VEGF receptor 2 signaling pathways in vitro and in
      vivo.
AB  - Angiogenesis plays an important role in various pathological conditions such as
      cancer via excessive delivery of oxygen and nutrients. Recent studies have
      demonstrated that understanding the molecular basis of natural agents in
      angiogenesis is critical for the development of promising cancer therapeutics. In
      this study, auriculasin, an active component from Flemingia philippinensis, was
      found to exert strong anti-angiogenesis activity. Treatment with auriculasin
      suppressed proliferation of human umbilical vein endothelial cells (HUVECs) by
      modulating expression of Bcl-2, Bcl-XL, and vascular endothelial growth factor
      (VEGF). Further, auriculasin inhibited VEGF-induced chemotactic migration,
      invasion, and capillary-like structure formation of endothelial cells. In
      addition, auriculasin abrogated VEGF-induced vascular network formation around
      rat aortic rings as well as blocked accumulation of hemoglobin, endothelial cells
      and VEGF in the Matrigel plug of C57BL/6 mice. The inhibitory effect of
      auriculasin on angiogenesis was well correlated with inhibition of VEGF receptor
      2 (VEGFR2) activation as well as phosphorylation of intracellular downstream
      protein kinases of VEGFR2 containing Akt, mammalian target of rapamycin (mTOR),
      phosphoinositide 3-kinase (PI3K), p-38, extracellular signal-related kinase
      (ERK), and Src. Taken together, this study reports that auriculasin potently
      inhibits angiogenesis by modulating VEGFR2-related signaling pathways, which
      further validates its great potential in clinical applications.

PMID- 30236599
TI  - Protective effects of Coreopsis tinctoria flowers phenolic extract against D
      galactosamine/lipopolysaccharide -induced acute liver injury by up-regulation of
      Nrf2, PPARalpha, and PPARgamma.
AB  - Coreopsis tinctoria flowers, a well-known medicinal and edible plant, have been
      reported to possess antioxidant and anti-inflammatory activities. However, its
      protective effects and underlying mechanisms on liver injury remain unclear. The
      aim of this study was to investigate the underlying mechanisms by which Coreopsis
      tinctoria flowers phenolic extract (CTP) alleviated D-galactosamine and
      lipopolysaccharide (D-GalN/LPS) induced acute liver injury in mice. Our results
      showed that pretreatment with CTP improved liver histology while decreased levels
      of serum aminotransferase and malondialdehyde. CTP also increased levels of
      glutathione in D-GalN/LPS -induced acute liver injury mice by up-regulation of
      nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator
      activated receptor alpha (PPARalpha), and peroxisome proliferator-activated
      receptor gamma (PPARgamma). In conclusion, results suggested that CTP protected
      against D-GalN/LPS -induced acute liver injury by up-regulation of Nrf2,
      PPARalpha, and PPARgamma.

PMID- 30236600
TI  - The cigarette smoke components induced the cell proliferation and epithelial to
      mesenchymal transition via production of reactive oxygen species in endometrial
      adenocarcinoma cells.
AB  - Cigarette smoke (CS) causes about 480,000 deaths each year worldwide and is well
      known to have harmful effects on the human body, leading to heart disease,
      stroke, lung cancer, and cardiovascular problems. In the present study, the
      effects of acrylonitrile (AN), benzo(a)pyrene (B(a)P), formaldehyde (FOR),
      isoprene (ISO), nicotine-derived nitrosamine ketone (NNK), which are the main
      components of CS, on the proliferation, invasion, and the epithelial-mesenchymal
      transition (EMT) process of human Ishikawa endometrial adenocarcinoma cells were
      investigated. Treating Ishikawa cells with CS components resulted in increased
      cell growth and altered expression of cell cycle-related genes: the protein
      expression of cyclin D & E increased, while the levels of p21 & p27 were reduced
      following treatment of these five CS components. In addition, CS components
      increased the invasion capacity of Ishikawa cells. The expression of the
      epithelial markers, E-cadherin and occludin, were significantly decreased, while
      the expression of the mesenchymal marker, N-cadherin, was significantly increased
      by CS components. In dichloro-dihydro-fluorescein diacetate (H2DCF-DA) assay, ROS
      production increased by treatment of CS components. The CS components activated
      the ROS-p38 MAPK-EMT pathway by increasing the level of phosphorylated p38 MAPK
      and p44/42 (ERK1/2), and by up-regulating Snail and Slug, the transcription
      factors for EMT. Taken together, these results indicate that CS components can
      promote progression of endometrial adenocarcinoma via increasing cell
      proliferation and the ROS-mediated EMT process.

PMID- 30236603
TI  - Accelerated silent echo-planar imaging.
AB  - PURPOSE: The standard approach to Echo-Planar Imaging (EPI) is to use trapezoidal
      readout (RO) gradients with blipped phase-encoding (PE) gradients. Sinusoidal RO
      gradients with constant PE gradients can reduce acoustic noise. However, this
      sequence, originally introduced by Mansfield et al., constitutes major challenges
      for Cartesian parallel imaging techniques. In this study two alternatives to
      reconstruct a non-blipped EPI are proposed and evaluated. THEORY AND METHODS: The
      first method separates the acquired k-space data into odd and even echoes and
      applies Cartesian GRAPPA separately to each partial data set. Afterwards, the
      resulting reconstructed data sets for each echo are summed in image space. In the
      second method, an iterative parallel-imaging algorithm is used to reconstruct
      images from the highly non-Cartesian data samples. RESULTS: Compared to blipped
      EPI, the first method reduces image SNR depending on the acceleration factor
      between 11% and 60%. For an acceleration factor of 3 folding artefacts appear.
      The second method produces slight fold-over artefacts although image SNR is on
      the same level as the blipped approach. CONCLUSION: In this study, we have
      introduced two new approaches to EPI that allow the use of Cartesian parallel
      imaging in conjunction with continuous data sampling. In addition to providing a
      reduction in acoustic noise compared to the standard blipped PE EPI sequence, the
      proposed techniques improve sampling efficiency, resulting in a reduction of the
      echo-spacing. Of the two methods, the second approach, based on an iterative
      image reconstruction, provides higher SNR, but requires a longer reconstruction
      time.

PMID- 30236604
TI  - Potential role of stem cells in disease prevention based on a murine model of
      experimental necrotizing enterocolitis.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating disease of newborns,
      and despite years of research, there is no known cure. The mortality rate of
      infants with NEC remains as high as 20%-30%. Babies who survive NEC frequently
      have long term complications including short gut syndrome, developmental delays
      and neurological sequelae. Unfortunately, despite much research over the past
      years, the precise pathogenesis of the disease is still not completely
      understood. METHODS: Our laboratory has focused on identifying novel therapies to
      prevent the disease, including the use of stem cells (SC), heparin-binding
      epidermal growth factor-like growth factor (HB-EGF) and recently, stem cell
      derived-exosomes, a type of nanovesicle, to combat this illness. RESULTS: We have
      outlined the major SC lines and data suggesting potential benefit as a curative
      or preventive approach for NEC as well as describing several new therapeutic
      strategies, including stem cell derived- exosomes and HB-EGF for decreasing the
      incidence and severity of this disease in rat models in our lab. CONCLUSION:
      Overall, our lab has demonstrated that these different types of SC equivalently
      reduce the incidence and severity of NEC and equally preserve intestinal barrier
      function during NEC. We have previously demonstrated that AF-MSC can protect the
      intestines from intestinal injury and may therefore hold strong therapeutic
      potential for the prevention of NEC. Most recently, our work with stem cell
      derived-exosomes has shown them to be equivalent to their derived SC lines in
      decreasing the incidence of this disease.

PMID- 30236605
TI  - Prevention and management of recurrent postoperative Hirschsprung's disease
      obstructive symptoms and enterocolitis: Systematic review and meta-analysis.
AB  - BACKGROUND/PURPOSE: The purpose of this study was to review the management of
      obstructive symptoms and enterocolitis (HAEC) following pull-through for
      Hirschsprung's disease. METHODS: A systematic review and meta-analysis (1992
      2017) was performed. Included studies were: randomized controlled trials (RCT),
      retrospective/prospective case-control (C-C), case-series (C-S). Random-effect
      model was used to produce risk ratio (RR) [95% CI]. P < 0.05 was considered
      significant. RESULTS: Twenty-nine studies were identified. Routine postoperative
      dilatations (5 C-S, 2 C-C; 405 patients): no effect on stricture incidence (RR
      0.3 [0.02-5.7]; p = 0.4). Routine postoperative rectal irrigations (2 C-C; 172
      patients): reduced HAEC incidence (RR 0.2 [0.1-0.5]; p = 0.001). Posterior
      myotomy/myectomy (4 C-S; 53 patients): resolved obstructive symptoms in 79% [60.6
      93.5] and HAEC in 80% [64.1-92.1]. Botulinum toxin injection (9 C-S; 166
      patients): short-term response in 77.3% [68.2-85.2], long-term response in 43.0%
      [26.9-59.9]. Topical nitric oxide (3 C-S; 13 patients): improvement in 100% of
      patients. Probiotic prophylaxis (3 RCT; 160 patients): no reduction in HAEC (RR
      0.6 [0.2-1.7]; p = 0.3). Anti-inflammatory drugs (1 C-S, sodium cromoglycate; 8
      patients): improvement of HAEC in 75% of patients. CONCLUSIONS: Several
      strategies with variable results are available in patients with obstructive
      symptoms and HAEC. Routine postoperative dilatations and prophylactic probiotics
      have no role in reducing the incidence of postoperative obstructive symptoms and
      HAEC. TYPE OF STUDY: Systematic review and meta-analysis. LEVEL OF EVIDENCE:
      Level II.

PMID- 30236607
TI  - Pioneering women in American pediatric surgery.
AB  - Women were among the pioneers in American pediatric surgery in its early decades.
      Once in practice, Benjy Brooks (Houston) and Jessie Ternberg (St. Louis) became
      identified with the specialty in their adopted communities, and Rowena Spencer in
      her hometown of New Orleans. Louise Schnaufer in Philadelphia, Kathryn Anderson
      in Washington, D.C., and Patricia Donahoe in Boston were all prominent surgeons
      at leading children's specialty hospitals in the country. Schnaufer was the
      unsung stalwart in general and thoracic surgery at the Children's Hospital of
      Philadelphia. Anderson became Surgeon-in-Chief in Los Angeles, and later the
      first woman leader of both professional societies in pediatric surgery as well as
      first woman President of the American College of Surgeons. Donahoe developed a
      spectacular academic career and became one of the outstanding surgical scientists
      in the country. Each faced gender discrimination at several stages of their
      careers: medical school enrollments that limited spots for women; widespread bias
      against women training in surgery and pediatric surgery; and the absence of woman
      role models and mentors. It is instructive and inspiring to review their
      individual stories that play an important part of the history of the specialty.

PMID- 30236606
TI  - Refinement in the analysis of motion within low-cost laparoscopic simulators of
      differing size: Implications on assessing technical skills.
AB  - BACKGROUND: Simulation is becoming more important in the teaching and assessment
      of technical skills. The purpose of this study was to refine the use of motion
      analysis parameters (MAPs) to assess performance of a defined task in low-cost
      pediatric laparoscopic simulators of differing size. METHODS: 105 participants
      performed a defined intracorporeal suturing task in large and small pediatric
      laparoscopic simulators. Outcomes included MAPs - path length, extreme velocity
      events, and extreme acceleration events in all available degrees of freedom for
      novices, intermediates, and experts. ANOVA p <0.05 was judged significant.
      RESULTS: In the smaller simulator, all MAPs discriminated between expertise
      groups in all degrees of freedom. In the larger simulator, all but one MAP
      discriminated between expertise groups. Experts demonstrated the greatest
      variability in performance between the larger and smaller simulators. CONCLUSION:
      Analysis of motion in the performance of a defined intracorporeal suturing task
      allowed discrimination between novices, intermediates, and experts in large and
      small low-cost pediatric laparoscopic simulators. Further refinement in MAPs will
      determine their role in surgical education. LEVEL OF EVIDENCE: Not applicable.

PMID- 30236608
TI  - Inhibition of Aeromonas hydrophila-induced intestinal inflammation and mucosal
      barrier function damage in crucian carp by oral administration of Lactococcus
      lactis.
AB  - This study explored the immunomodulatory effect and inhibition effects of the
      candidate probiotic Lactococcus lactis 16-7, which was isolated from crucian
      carp, on Aeromonas hydrophila infection in crucian carp. The experimental fish
      were divided into two groups; one was fed a diet supplemented with L. lactis,
      while the other was fed the control probiotic-free diet. After feeding for 42 d
      with the experimental diets, the fish that received the diet supplemented with
      probiotics exhibited a significantly enhanced serum superoxide dismutase
      activity, phagocytic activities of innate immune cells, and the expression levels
      of immune-related genes [interferon-gamma (INF-gamma), interleukin-1beta (IL
      1beta), interleukin-11 (IL-11), tumour necrosis factor alpha (TNF-alpha) and
      myeloid differentiation factor 88 (MyD88)], indicating that L. lactis 16-7 could
      activate the non-specific immune system of crucian carp. At the end of the
      feeding trial, the crucian carps in each group were orally infected with A.
      hydrophila NJ-35. The results show that L. lactis 16-7 could prevent the increase
      in d-lactic acid concentration and inflammatory response caused by A. hydrophila
      in crucian carp. Compared with A. hydrophila group, L. lactis 16-7 preserved the
      integrity of intestinal villi and mitigated A. hydrophila-induced reduce in the
      transcriptional levels of tight junction (TJ) proteins zonula occludens-1 (ZO-1)
      and occludin, indicating that L. lactis 16-7 could reduce intestinal mucosal
      barrier damage and inflammation induced by A. hydrophila in crucian carp. In
      addition, L. lactis 16-7 could effectively antagonize the colonization of A.
      hydrophila in the intestine. Overall, these data clearly indicate that L. lactis
      16-7 has the potential to be developed as a probiotic agent against A. hydrophila
      infection in aquaculture.

PMID- 30236609
TI  - Durability of Stroke Prevention with Carotid Endarterectomy and Carotid Stenting.
AB  - BACKGROUND: Carotid artery stenting remains an effective alternative to carotid
      endarterectomy for stroke prevention; however, the long-term durability of
      carotid artery stenting remains poorly defined. We performed a 10-year "real
      world" comparative analysis of carotid endarterectomy and carotid artery stenting
      to help evaluate the success of these procedures in preventing late ischemic
      stroke events. METHODS: This was a single-center retrospective review of 996
      patients (symptomatic and asymptomatic) treated with carotid endarterectomy or
      carotid artery stenting from January 2001 through December 2011 at a tertiary
      academic medical center. All-cause death, stroke, and myocardial infarction event
      rates were analyzed using log-rank analysis. RESULTS: Among the 996 patients
      treated with carotid endarterectomy (n = 787) or carotid artery stenting (n =
      209), the 30-day, 1-year, 5-year, and 10-year survival rates for carotid
      endarterectomy patients were 99.1%, 95.3%, 77.9%, and 54.8%; carotid artery
      stenting rates were 99.5%, 96.2%, 67.8%, and 40.2%, respectively (P = .005, at 10
      years). There was no significant difference in early stroke rates or myocardial
      infarction rates between the groups. Subgroup analysis comparing symptomatic
      status demonstrated no statistically significant differences in overall survival,
      stroke, or myocardial infarction rates at 10 years. In addition to reduced long
      term overall survival, carotid artery stenting patients had a higher long-term
      restenosis rate as compared to carotid endarterectomy (6.3% vs 2.8%, P < .0001)
      and reduced restenosis-free survival (P = .01). CONCLUSIONS: Early death, stroke,
      and myocardial infarction rates are comparable after carotid endarterectomy and
      carotid artery stenting. Carotid artery stenting is an effective means of
      preventing stroke among patients with carotid artery stenosis. Symptomatic status
      does not seem to affect rates of stroke, myocardial infarction, or death. Carotid
      endarterectomy continues to be the preferred long-term solution for extracranial
      carotid artery occlusive disease as it is associated with better long-term
      survival and lower restenosis rates.

PMID- 30236610
TI  - Outcomes of patients admitted with ventricular arrhythmias and sudden cardiac
      death in the United States.
AB  - BACKGROUND: Mortality caused by ventricular arrhythmias (VAs) remains a problem
      of epidemic proportions. Understanding current trends on admission of VA, patient
      characteristics, morbidity, mortality, and health care utilization could help us
      improve allocation of health care resources and risk prediction. OBJECTIVE: The
      purpose of this study was to investigate clinical outcomes of VA, including
      ventricular tachycardia (VT), implantable cardioverter-defibrillator (ICD)
      shocks, and sudden cardiac death (SCD); and to identify predictors of morbidity
      and mortality, patterns of utilization of ICD and VT ablation, and the impact of
      such metrics on overall health care utilization. METHODS: From 2010-2015, we
      identified 290,998 VA hospitalizations, which were stratified into group 1:
      normal heart; group 2: ischemic heart disease (IHD); group 3: nonischemic heart
      disease (non-IHD); group 4: ICD shocks; and group 5: SCD (cardiac arrest without
      ICD shock). RESULTS: The number of admissions for VA decreased during the study
      period (except for patients with SCD and ICD shock, which increased); in-hospital
      mortality in patients admitted with VA and SCD increased; utilization of VT
      ablation in patients with ICD shocks and IHD increased; ICD implantation
      decreased in non-IHD patients and IHD patients; and admission for SCD was the
      strongest predictor of in-hospital mortality, followed by patients with non-IHD,
      patients with ICD shocks, and all patients with a Charlson comorbidity index >=2.
      CONCLUSION: We report a decrease in admissions for VA, decreased ICD utilization,
      a change in pattern of VT ablation utilization, and an increase of in-hospital
      mortality in SCD patients. Predictors of adverse outcomes identified in our study
      should be considered when developing risk models for patients undergoing risk
      assessment for SCD.

PMID- 30236611
TI  - Incidence and Mortality of Pemphigus in France.

PMID- 30236612
TI  - IL-10-producing Regulatory B Cells Are Decreased in Patients with Atopic
      Dermatitis.

PMID- 30236613
TI  - A novel p.Ser108LeufsTer15 SOD1 mutation leading to the formation of a premature
      stop codon in an apparently sporadic ALS patient: insights into the underlying
      pathomechanisms.
AB  - We report an apparently sporadic amyotrophic lateral sclerosis patient carrying a
      heterozygous novel frameshift SOD1 mutation (p.Ser108LeufsTer15), predicted to
      cause a premature protein truncation. RT-PCR analysis of SOD1 mRNA and SDS
      PAGE/Western blot analysis of PBMC demonstrated that mRNA from the mutant allele
      is expressed at levels similar to those of the wild-type allele, but the
      truncated protein is undetectable also in the insoluble fraction and after
      proteasome inhibition. Accordingly, the dismutation activity in erythrocytes is
      halved. Thus, the pathogenic mechanism associated with this mutation might be
      based on an insufficient activity of SOD1 that would make motor neurons more
      vulnerable to oxidative injury. However, it cannot be excluded that
      p.Ser108LeufsTer15 SOD1 is present in the nervous tissue and, being less charged
      and hence having less repulsive forces than the wild-type protein, may trigger
      toxic mechanisms as a consequence of its propensity to aggregate.

PMID- 30236614
TI  - Self-initiated versus instructed cheating in the physiological Concealed
      Information Test.
AB  - The validity of the Concealed Information Test (CIT) to detect recognition of
      critical details has been demonstrated in hundreds of laboratory studies. These
      studies, however, lack the factor of deliberate intent to deceive. This disparity
      between research and practice may affect the generalizability of laboratory based
      CIT findings. In the current study, 65 out of 174 participants cheated on their
      own initiative in a trivia quiz. These self-initiated cheaters were compared to
      68 participants who were explicitly requested to cheat. Skin conductance, heart
      rate, and respiration were found to detect concealed information related to
      cheating. No significant differences emerged between self-initiated and
      instructed cheaters, supported by Bayesian statistics showing substantial
      evidence for the null hypothesis. The data demonstrate that the validity of the
      CIT is not restricted to instructed deception. This finding is encouraging from
      an ecological validity perspective and may pave the way for further field
      implementation of memory detection.

PMID- 30236616
TI  - Use of social networking sites, electronic cigarettes, and waterpipes among
      adolescents.
AB  - OBJECTIVES: Electronic cigarettes (e-cigarettes) and waterpipes are gaining in
      popularity among adolescents in tandem with the increasing popularity of social
      networking sites (SNSs). The objective of this study was to examine the
      associations between the use of SNSs and e-cigarette and waterpipe use among
      adolescents, and to test whether these associations are independent of tobacco
      cigarette smoking. STUDY DESIGN: A province-wide school-based cross-sectional
      study. METHODS: Data were derived from the 2013 Ontario Student Drug Use and
      Health Survey. Our analyses included representative data from 2841 high school
      students across Ontario, Canada, who completed the questionnaire that included
      measures of lifetime use of e-cigarette and past-year use of waterpipe. RESULTS:
      Nearly 14.6% of students reported having smoked an e-cigarette in their lifetime
      and 12.2% reported having smoked a waterpipe in the past year. After adjusting
      for various covariates, daily use of SNSs of at least 1 h/day was associated with
      greater odds of e-cigarette use (odds ratios ranged from 3.31 for SNS use of 1
      h/day to 3.43 for >=3 h/day), while daily use of SNSs of at least 2 h was
      associated with waterpipe use (odds ratios of 3.28 for SNS use of 2 h/day and
      2.83 for use of >=3 h/day). The observed associations remained significant after
      further adjusting for tobacco cigarette smoking. CONCLUSIONS: The use of SNSs was
      positively associated with e-cigarette and waterpipe use, independent of tobacco
      cigarette smoking. These findings highlight the need for including SNSs in
      ongoing prevention and intervention efforts.

PMID- 30236615
TI  - Document of recommendations of the SEA 2018. Lifestyle in cardiovascular
      prevention.
AB  - Lifestyle is a complex concept that includes aspects external to ourselves that
      can modulate and influence our health. The knowledge of the relationship between
      lifestyle and cardiovascular risk does not attain the level of evidence achieved
      with clinical trials with drugs, because clinical studies are scarce and mainly
      of observational nature, albeit based on large cohorts. Nutritional epidemiology
      has the added difficulty of being based mostly on subjective dietary recall
      methods to ascertain nutrient and food intake over time, with the additional
      problems of incomplete data collection, variable measurements of adherence due to
      seasonal and geographical differences in food composition, and the changing
      eating behavior that human beings have over time. The purpose of this document is
      to carry out an updated and hierarchical review of the relationship between
      lifestyle and cardiovascular disease based on current evidence, paying attention
      to three aspects that are of great pathogenic importance and are directly
      modifiable: physical activity, tobacco consumption, and diet. With this, we
      intend to update the knowledge on this relationship, construct evidence-based
      recommendations, and provide a simple tool for clinical practice especially
      directed to health professionals involved in the care of people at cardiovascular
      risk, defining simple and easy strategies for individuals who receive advice for
      the primary and secondary prevention of cardiovascular diseases.

PMID- 30236617
TI  - Accelerating the estimation of 3D spatially resolved T2 distributions.
AB  - Obtaining quantitative, 3D spatially-resolved T2 distributions (T2 maps) from
      magnetic resonance data is of importance in both medical and porous media
      applications. Due to the long acquisition time, there is considerable interest in
      accelerating the experiments by applying undersampling schemes during the
      acquisition and developing reconstruction techniques for obtaining the 3D T2 maps
      from the undersampled data. A multi-echo spin echo pulse sequence is used in this
      work to acquire the undersampled data according to two different sampling
      patterns: a conventional coherent sampling pattern where the same set of lines in
      k-space is sampled for all equally-spaced echoes in the echo train, and a
      proposed incoherent sampling pattern where an independent set of k-space lines is
      sampled for each echo. The conventional reconstruction technique of total
      variation regularization is compared to the more recent techniques of nuclear
      norm regularization and Nuclear Total Generalized Variation (NTGV)
      regularization. It is shown that best reconstructions are obtained when the data
      acquired using an incoherent sampling scheme are processed using NTGV
      regularization. Using an incoherent sampling pattern and NTGV regularization as
      the reconstruction technique, quantitative results are obtained at sampling
      percentages as low as 3.1% of k-space, corresponding to a 32-fold decrease in the
      acquisition time, compared to a fully sampled dataset.

PMID- 30236618
TI  - Abscisic acid and nitric oxide modulate cytoskeleton organization, root hair
      growth and ectopic hair formation in Arabidopsis.
AB  - Abscisic acid (ABA) and nitric oxide (NO) are two plant growth regulators that
      participate in many signaling cascades in different organs all along the plant
      life. Here, we were interested in deciphering the effects of ABA and NO on the
      cytoskeleton organization in a model of polarized cell growth like root hairs.
      Arabidopsis roots were exposed to different concentrations of ABA, and the length
      of primary root, epidermal cells and root hairs were measured. The NO
      concentration was detected with the NO-specific fluorescent probe DAF-FM DA. To
      quantify the effects of ABA and NO on cytoskeleton, Arabidopsis seedlings
      expressing GFP-MAP4 were used to analyze microtubules (MTs) orientation. Changes
      in cytoplasmic streaming were quantified through fluorescence recovery after
      photobleaching (FRAP) experiments using confocal laser scanning microscopy (CLSM)
      and the probe fluorescein diacetate (FDA). Results indicate that ABA decreases
      root hair length and induces the differentiation of atrichoblasts into
      trichoblasts, increasing root hair density. ABA also triggers an increase of NO
      level in root hairs. Both, ABA and NO affect MT organization in root hairs. While
      root hairs show MT orientation close to the longitudinal axis in control roots,
      ABA and NO treatments induce the oblique orientation of MTs. In parallel,
      cytoplasmic flow, executed by actin cytoskeleton, is enhanced by NO, in an ABA
      independent manner. For all experimental conditions assayed, basal levels of NO
      are required to keep MT organization and cytoplasmic streaming. Our findings
      support ABA and NO as key modulators of growth and ectopic formation of root
      hairs through actions on cytoskeleton functions.

PMID- 30236620
TI  - Clickable conjugates of bile acids and nucleosides: Synthesis, characterization,
      in vitro anticancer and antituberculosis studies.
AB  - A series of clickable bile acid-nucleosides conjugates linked directly or via
      amino acid linker were synthesized, and characterized by spectroscopic techniques
      such as 1H NMR, 13C NMR, FT-IR, HRMS and HPLC. The synthesized compounds 6a-p
      were screened for their in vitro anticancer property against a panel of three
      cancer cell lines (PC-3, MCF-7, IMR-32). In addition, the synthesized derivatives
      were also tested for their antimycobacterial activity against Mycobacterium
      tuberculosis H37Rv (ATCC 27294 strain). Among the screened compounds, cholic acid
      uridine clicked conjugate (6c), and cholic acid-uridine clicked conjugate liked
      via phenylalanine moiety (6m) were found to be most active against MCF-7 and IMR
      32 exhibiting an IC50 value of 8.084 and 8.71 uM, respectively. The
      antimycobacterial study of the synthesized conjugates revealed all the conjugates
      to be active with MIC values in the range of 4.09-15.41 uM. Deoxycholic acid
      adenosine clicked conjugate (6b) showed most promising antituberculosis property
      with MIC value of 4.09 uM. Most of the synthesized conjugates were found to be
      safe at 50 uM against normal human embryonic kidney (HEK 293 T) cell line.

PMID- 30236619
TI  - Metabolomics profiling reveals profound metabolic impairments in mice and
      patients with Sandhoff disease.
AB  - Sandhoff disease (SD) results from mutations in the HEXB gene, subsequent
      deficiency of N-acetyl-beta-hexosaminidase (Hex) and accumulation of GM2
      gangliosides. SD leads to progressive neurodegeneration and early death. However,
      there is a lack of established SD biomarkers, while the pathogenesis etiology
      remains to be elucidated. To identify potential biomarkers and unveil the
      pathogenic mechanisms, metabolomics analysis with reverse phase liquid
      chromatography (RPLC) was conducted. A total of 177, 112 and 119 metabolites were
      found to be significantly dysregulated in mouse liver, mouse brain and human
      hippocampus samples, respectively (p < .05, ID score > 0.5). Principal component
      analysis (PCA) analysis of the metabolites showed clear separation of
      metabolomics profiles between normal and diseased individuals. Among these
      metabolites, dipeptides, amino acids and derivatives were elevated, indicating a
      robust protein catabolism. Through pathway enrichment analysis, we also found
      alterations in metabolites associated with neurotransmission, lipid metabolism,
      oxidative stress and inflammation. In addition, N-acetylgalactosamine 4-sulphate,
      key component of glycosaminoglycans (GAG) was significantly elevated, which was
      also confirmed by biochemical assays. Collectively, these results indicated major
      shifts of energy utilization and profound metabolic impairments, contributing to
      the pathogenesis mechanisms of SD. Global metabolomics profiling may provide an
      innovative tool for better understanding the disease mechanisms, and identifying
      potential diagnostic biomarkers for SD.

PMID- 30236621
TI  - Alterations in Layer-Specific Left Ventricular Global Longitudinal and
      Circumferential Strain in Patients With Aortic Stenosis: A Comparison of Aortic
      Valve Replacement versus Conservative Management Over a 12-Month Period.
AB  - BACKGROUND: Impairment in left ventricular (LV) systolic strain in aortic
      stenosis (AS) is well documented. However, alterations in layer-specific LV
      global longitudinal strain (GLS) and global circumferential strain (GCS) and
      their recovery following surgical aortic valve replacement (AVR) have not been
      established. The aim of this study was to examine layer-specific changes in GLS
      and GCS in patients with AS undergoing AVR and compare these patients with those
      managed conservatively over 12 months. METHODS: Eighty-six patients (mean age,
      68.8 +/- 12 years; 60 men) with AS (19 mild, 15 moderate, and 52 severe) were
      prospectively recruited. Patients with coronary disease or other significant
      valvular disease were excluded. Forty patients (46.5%) with severe AS underwent
      AVR. All patients underwent baseline echocardiography. Patients managed
      conservatively underwent follow-up echocardiography at 12 months. Patients
      undergoing AVR underwent follow-up echocardiography at 1 week and 3, 6, and 12
      months after AVR. RESULTS: There was worsening in subendocardial but not
      subepicardial or transmural GLS even in mild AS (-20.9 +/- 1.0% vs -20.6 +/-
      0.8%, P = .012). In moderate AS, worsening in subendocardial (-19.6 +/- 0.9% vs 
      18.2 +/- 1.5%, P = .003), subepicardial (-14.9 +/- 1.0% vs -13.8 +/- 1.2%, P =
      .004), and transmural (-17.1 +/- 0.9% vs -15.8 +/- 1.3%, P = .03) GLS and a trend
      toward significant worsening in subendocardial GCS (-29.8 +/- 5.16% vs -27.5 +/-
      5%, P = .054) were seen. Conservatively managed patients with severe AS had
      significant worsening in subendocardial (-16.1 +/- 1.6% vs -13.9 +/- 2.6%, P =
      .021), subepicardial (-11.6 +/- 1.1% vs -10.1 +/- 2.1%, P = .027), and transmural
      (-13.6 +/- 1.3% vs -11.8 +/- 2.3%, P = .02) GLS and subendocardial (-24.9 +/-
      3.6% vs -20.8 +/- 4.5%, P = .002) and transmural (-16.9 +/- 1.7% vs -14.3 +/-
      3.5%, P = .04) GCS on follow-up. Patients after AVR demonstrated significant
      improvement in GLS (from 3 months) and GCS (from 6 months) in both myocardial
      layers. CONCLUSIONS: Patients with AS managed conservatively had worsening of GLS
      over 12 months despite preserved LV ejection fraction, detected earliest in the
      subendocardial layer. GCS became progressively impaired in moderate and severe
      AS. Improvement in LV strain after AVR was seen earlier with GLS (from 3 months)
      than with GCS (from 6 months) in both myocardial layers.

PMID- 30236623
TI  - Disparities in Wait-List Outcomes for Adults With Congenital Heart Disease Listed
      for Heart Transplantation Before and Since Revision of Status I Listing.
AB  - Medical and surgical advances in the late 20th century that allowed the majority
      of children born with congenital heart disease (CHD) to survive have resulted in
      a shift of the burden of morbidity and mortality into adulthood. Heart failure is
      the leading cause of death in adults with CHD. This study aimed to address the
      gap in understanding of outcomes of adults with CHD who have heart failure and
      are listed for heart transplantation compared with those without CHD. The study
      analyzed data from the US Scientific Registry of Transplant Recipients database,
      categorized by the listing era (on/before or after January 19, 1999). The primary
      combined outcome was death while waiting for an organ or delisting due to
      worsening clinical condition. Overall, there was a significant decrease in the
      probability of the primary outcome in the current compared with the early era for
      both adults with CHD (13.2% vs 18.6%, p = 0.01) and non-CHD (12.1% vs 15.9%, p <
      0.0001). However, this improvement was only observed among adults with CHD listed
      in Status I, whereas adults without CHD saw significant improvement in both
      statuses I and II. Furthermore in the current era, when compared with their non
      CHD counterparts, adults with CHD continue to have worse wait-list outcomes
      irrespective of listing status. In conclusion, outcomes for adults with CHD
      listed for heart transplantation have improved since the revision of Status I
      listing in 1999. Despite such improvements there continues to be a significant
      disparity in wait-list outcomes between adults with compared with those without
      CHD.

PMID- 30236622
TI  - Differences in Initial Electrocardiographic Findings of Apical Takotsubo Syndrome
      According to the Time from Symptom Onset.
AB  - No previous study has examined the differences in patient characteristics and
      initial electrocardiographic findings of Takotsubo syndrome (TTS) according to
      the time from onset to electrocardiography. Using the Tokyo Cardiovascular Care
      Unit network registry 2011-2012, we retrospectively identified 106 apical TTS
      patients in whom symptom onset time was specified, and classified the patients
      into 5 groups according to the time from onset to the initial
      electrocardiography: <3 hours (n = 45), 3 to 6 hours (n = 20), 6 to 12 hours (n =
      12), 12 to 24 hours (n = 13), and >=24 hours (n = 16). There was no significant
      difference across the groups in age, gender, symptoms, triggers, vital signs,
      blood tests, or in-hospital outcomes. In the electrocardiographic findings, ST
      elevation was more frequent in leads V2-V4 than in the other leads, especially in
      the <24 hour groups, but did not differ significantly across groups. T-wave
      inversion was more frequent in leads V3-V6, especially in the >=24 hour group,
      and differed significantly across groups. The total number of leads with T-wave
      inversion was significantly larger in the >=24 hour group than in the <24 hour
      groups (mean, 5.9 leads vs 1.5 to 2.9 leads; p < 0.001). Isolated ST-elevation
      was the most frequent pattern of ST-T change in precordial leads (42% to 56%) in
      the <24 hour groups, while isolated T-wave inversion was the most frequent (44%)
      in the >=24 hour group (p = 0.018). Neither ST-elevation nor T-wave inversion was
      observed in precordial leads in 10 (9%) patients. In conclusion, our results
      suggest that the initial electrocardiographic findings of apical TTS are affected
      by the time from onset to electrocardiography and display a wide variation in ST
      T changes.

PMID- 30236625
TI  - Refining indications and access in transcatheter mitral valve-in-valve
      replacement.

PMID- 30236626
TI  - Letter by Derimay et al. regarding the article, "A randomized trial comparing two
      stent sizing strategies in coronary bifurcation treatment with bioresorbable
      vascular scaffolds - The Absorb Bifurcation Coronary (ABC) trial" by Rampat et
      al.

PMID- 30236624
TI  - Iliofemoral peripheral orbital atherectomy for optimizing TAVR access: An
      innovative strategy in the absence of alternative access options.
AB  - Suboptimal iliofemoral artery access requiring alternative trans-catheter aortic
      valve replacement (TAVR) access is still encountered in 10-20% of subjects
      undergoing TAVR. Attempting suboptimal vascular access may result in excessive
      vessel injury, bleeding and even death. Reported is an innovative procedure to
      address suboptimal heavily calcified iliofemoral access by using Diamondback 360
      peripheral orbital atherectomy (POA) to ablate heavy endoluminal vascular
      calcifications followed by balloon angioplasty. This approach enabled us to
      successfully deploy TAVR in extremely challenging iliofemoral anatomies that
      would otherwise be rendered prohibitive. The technical aspects of this procedure
      are delineated accompanied by a descriptive case of such procedure.

PMID- 30236627
TI  - Revisiting Panda 100, the first archaeological chimpanzee nut-cracking site.
AB  - Archaeological recovery of chimpanzee Panda oleosa nut cracking tools at the
      Panda 100 (P100) and Noulo sites in the Tai Forest, Cote d'Ivoire, showed that
      this behavior is over 4000 years old, making it the oldest known evidence of non
      human tool use. In 2002, the first report on the lithic material from P100 was
      directly compared to early hominin stone tools, highlighting their similarities
      and proposing the name 'Pandan' for the chimpanzee material. Here we present an
      expanded and comprehensive technological, microscopic, and refit analysis of the
      late twentieth century lithic assemblage from P100. Our re-analysis provides new
      data and perspectives on the applicability of chimpanzee nut cracking tools to
      our understanding of the percussive behaviors of early hominins. We identify
      several new refit sets, including the longest (>17 m) hammerstone transport seen
      in the chimpanzee archaeological record. We provide detailed evidence of the
      fragmentation sequences of Panda nut hammerstones, and characterize the
      percussive damage on fragmented material from P100. Finally, we emphasize that
      the chimpanzee lithic archaeological record is dynamic, with the preservation of
      actual hammerstones being rare, and the preservation of small broken pieces more
      common. P100 - the first archaeological chimpanzee nut cracking lithic assemblage
      - provides a valuable comparative sample by which to identify past chimpanzee
      behavior elsewhere, as well as similar hominin percussive behavior in the Early
      Stone Age.

PMID- 30236629
TI  - In Reply to 'Benefit of Eculizumab Compared to Standard of Care Still Unproven in
      C3 Glomerulopathy'.

PMID- 30236628
TI  - Mutational spectra and mutational signatures: Insights into cancer aetiology and
      mechanisms of DNA damage and repair.
AB  - Reporter gene assays, in which a single mutation from each experiment can
      contribute to the assembly of a mutation spectrum for an agent, have provided the
      basis for understanding the mutational processes induced by mutagenic agents and
      for providing clues to the origins of mutations in human tumours. More recently
      exome and whole genome sequencing of human tumours has revealed distinct patterns
      of mutation that could provide additional clues for the causative origins of
      cancer. This can be tested by examining the mutational signatures induced in
      experimental systems by putative cancer-causing agents. Such signatures are now
      being generated in vitro in a number of different mutagen-exposed cellular
      systems. Results reveal that mutagens induce characteristic mutation signatures
      that, in some cases, match signatures found in human tumours. Proof of principle
      has been established with mutational signatures generated by simulated sunlight
      and aristolochic acid, which match those signatures found in human melanomas and
      urothelial cancers, respectively. In an analysis of somatic mutations in cancers
      for which tobacco smoking confers an elevated risk, it was found that smoking is
      associated with increased mutation burdens of multiple different mutational
      signatures, which contribute to different extents in different tissues. One of
      these signatures, mainly found in tissues directly exposed to tobacco smoke, is
      attributable to misreplication of DNA damage caused by tobacco carcinogens.
      Others likely reflect indirect activation of DNA editing by APOBEC cytidine
      deaminases and of an endogenous clock-like mutational process. The results are
      consistent with the proposition that smoking increases cancer risk by increasing
      the somatic mutation load although direct evidence for this mechanism is lacking
      in some cancer types. Thus, next generation sequencing of exomes or whole genomes
      is providing new insights into processes underlying the causes of human cancer.

PMID- 30236630
TI  - Benefit of Eculizumab Compared to Standard of Care Still Unproven in C3
      Glomerulopathy.

PMID- 30236631
TI  - Preferences for health economics presentations among vaccine policymakers and
      researchers.
AB  - PURPOSE: Measure the preferences of decision makers and researchers associated
      with the Advisory Committee on Immunization Practices (ACIP) regarding the
      recommended format for presenting health economics studies to the ACIP. METHODS:
      We conducted key informant interviews and an online survey of current ACIP work
      group members, and current and previous ACIP voting members, liaison
      representatives, and ex-officio members to understand preferences for health
      economics presentations. These preferences included the presentation of results
      and sensitivity analyses, the role of health economics studies in decision
      making, and strategies to improve guidelines for presenting health economics
      studies. Best-worst scaling was used to measure the relative value of seven
      attributes of health economics presentations in vaccine decision making. RESULTS:
      The best-worst scaling survey had a response rate of 51% (n = 93). Results showed
      that summary results were the most important attribute for decision making (mean
      importance score: 0.69) and intermediate outcomes and disaggregated results were
      least important (mean importance score: -0.71). Respondents without previous
      health economics experience assigned sensitivity analysis lower importance and
      relationship of the results to other studies higher importance than the
      experienced group (sensitivity analysis scores: -0.15 vs. 0.15 respectively;
      relationship of the results: 0.13 vs. -0.12 respectively). Key informant
      interviews identified areas for improvement to include additional information on
      the quality of the analysis and increased role for liaisons familiar with health
      economics. CONCLUSION: Additional specificity in health economics presentations
      could allow for more effective presentations of evidence for vaccine decision
      making.

PMID- 30236632
TI  - Impact of the Hajj on pneumococcal carriage and the effect of various
      pneumococcal vaccines.
AB  - BACKGROUND: The Islamic Hajj pilgrimage is the largest annual mass gathering in
      the world. The overcrowding of people promotes the acquisition, spread and
      transmission of respiratory pathogens, including Streptococcus pneumoniae.
      METHODS: We conducted a methodological review according to the Preferred
      Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The
      objective was to summarize the available data regarding the prevalence of
      pneumococcal carriage among Hajj pilgrims and about carriage acquisition and
      circulation of S. pneumoniae among pilgrims before and after participating in the
      Hajj according to their vaccination status. RESULTS: Eight articles met
      eligibility criteria for pneumococcal carriage and impact of pneumococcal
      vaccination on carriage. Seven of them showed a significant increase in
      nasopharyngeal carriage of pneumococci following the pilgrimage, with acquisition
      rates ranging from 18 to 36%. Serotypes 3, 19F and 34 are the most common. A
      significant increase in antibiotic resistant strains was observed following
      participation in the Hajj. A lower prevalence was found in pilgrims treated with
      antibiotics, those who used a hand sanitizer, or those who washed their hands
      more frequently than usual. An increased carriage of pneumococcal serotypes
      included in pneumococcal vaccines (10-valent pneumococcal conjugate vaccine
      (PCV10), 13-valent pneumococcal conjugate vaccine (PCV13), 23-valent pneumococcal
      polysaccharide vaccine (PPV23)) was observed following participation in the Hajj.
      To date, no study has shown a significant reduction in pneumococcal carriage
      among pilgrims after vaccination with PPV23 or PCV. In fact, no significant
      difference was currently observed in the prevalence ratio of pneumococcal
      carriage between vaccinated and unvaccinated pilgrims. CONCLUSION: The studies
      analyzed in this review showed an increased carriage of pneumococcus in post-Hajj
      pilgrims compared to pre-Hajj pilgrims, including vaccine serotypes. Further
      studies are needed to investigate the possible relationships between carriage,
      disease and vaccine in pilgrims.

PMID- 30236633
TI  - Expenditures on vaccine-preventable disease surveillance: Analysis and evaluation
      of comprehensive multi-year plans (cMYPs) for immunization.
AB  - Despite the importance of vaccine-preventable disease (VPD) surveillance, little
      is known about the costs of monitoring disease. We used Comprehensive Multi-Year
      Plans for Immunization (cMYPs) - developed by countries following guidelines from
      the World Health Organization and United Nations Children's Fund - to estimate
      expenditures on VPD surveillance at the country level in 2015 US Dollars (USD) in
      63 low- and middle-income countries. To evaluate the reliability of cMYP
      estimates, we also compared cMYP data with findings from previous research
      studies and assessed whether countries explicitly budgeted for major categories
      of surveillance activities in their plans for immunization. According to our
      analysis of cMYPs, countries spent an annual median of $406,108 on VPD
      surveillance ($0.04 per capita and $1.47 per infant), with reported expenditures
      ranging from $1,098 (Kiribati) to $21,644,770 (Nigeria). However, the majority of
      countries failed to explicitly mention several key categories of surveillance
      activities in their plans, especially laboratory-related surveillance activities.
      Our results show a large amount of variation in surveillance expenditures (total,
      per capita, and per infant) between countries and provide insights to improve
      costing guidelines and practices.

PMID- 30236634
TI  - Evaluation of a 9-valent HPV vaccine in Sprague-Dawley rats: Nonclinical studies
      assessing general, reproductive, and developmental toxicity.
AB  - GARDASIL(r)9, a 9-valent vaccine against human papillomavirus (9vHPV), was
      developed to prevent diseases mediated by HPV types 6/11/16/18/31/33/45/52/58.
      During the development of the vaccine, three nonclinical safety studies were
      conducted to evaluate repeat-dose toxicity and prenatal and postnatal
      developmental toxicity in Sprague-Dawley rats. In all studies, the vaccine was
      administered via intramuscular injections of 0.5 mL (the human dose) divided
      equally into each quadriceps muscle. In the repeat-dose toxicity study, potential
      local and systemic toxic effects of the 9vHPV vaccine were evaluated after 4
      doses given 21 days apart and after a 21-day recovery period. In the prenatal
      study, virgin females were dosed at 5 and 2 weeks prior to mating and on
      Gestation Day [GD] 6 (3 total doses). Potential postnatal developmental toxicity
      of the vaccine formulation was evaluated after 4 total doses (premating to
      lactation). There were no treatment-related unscheduled deaths in any studies. In
      the 3-month repeat-dose toxicity study, no adverse effects in male or female rats
      were observed. Anticipated systemic effects representing immunological responses
      and local inflammatory reactions at the injection sites were noted in the vaccine
      treated groups, with a trend toward recovery by the end of the 21-day recovery
      period. In the prenatal developmental toxicity study, there was no evidence of
      toxicity in females given the vaccine. There were no effects on fertility or
      reproductive performance of the parental females and no evidence of developmental
      toxicity. In the postnatal study, there was no evidence of toxicity in vaccine
      treated females and no evidence of developmental toxicity based on standard
      postnatal parameters, including behavioral testing and reproductive performance.
      The vaccine induced antibody responses in all studies and vaccine-specific
      antibodies were detected in offspring in the developmental toxicity studies.
      These results support the favorable safety profile of GARDASIL(r)9.

PMID- 30236636
TI  - Hypospadias as a Chronic Illness.

PMID- 30236635
TI  - Distribution of rotavirus genotypes in Dhaka, Bangladesh, 2012-2016: Re-emergence
      of G3P[8] after over a decade of interval.
AB  - Group A rotavirus causes a substantial proportion of diarrhoea related deaths
      worldwide among children under five years. We analyzed rotavirus prevalence and
      genotypes distribution among patients admitted with diarrhoea at icddr,b hospital
      in Dhaka during 2012-16. Stool specimens (n = 1110) were collected from diarrhoea
      patients and tested for RVA antigen using enzyme immunoassay. Rotavirus positive
      samples were G (VP7) and P (VP4) genotyped by RT-PCR and sanger sequencing. Data
      on clinical manifestations were collected from icddr,b hospital surveillance
      system. A total of 351 (32%) patients were positive for rotavirus antigen, about
      half of those were children under two years old. During the study period, G1P[8]
      (27%) was the most prevalent strain, followed by G12P[8] (15%) and G9[P4] (9%).
      Mixed G or P genotypes were identified in a substantial proportion (23%) with few
      strains of rare combinations such as G1P[4], G1P[6], G2P[6], G2P[8], G9P[6]. The
      genotypic fluctuation was noteworthy; G12P[8] was the major strain in 2012-14 but
      sharply decreased in 2015-16 when G1P[8] became the most common strain. G3P[8] re
      emerged (17%) in 2016 after 11 years. Since the Government of Bangladesh has
      planned to include rotavirus vaccine in national immunization programme from
      2018, our data will provide baseline information on rotavirus genotypes in the
      pre-vaccination era to observe the selection pressure on genotypes in the post
      vaccination epoch.

PMID- 30236637
TI  - Relationship of preoperative intramedullary MRI signal intensity and dynamic
      factors with surgical outcomes of laminoplasty for cervical ossification of the
      posterior longitudinal ligament.
AB  - OBJECTIVE: We aimed to analyze the relationship of preoperative signal intensity
      on magnetic resonance imaging (MRI) and dynamic factor with surgical outcomes of
      laminoplasty for cervical ossification of the posterior longitudinal ligament
      (OPLL). PATIENTS AND METHODS: We retrospectively reviewed the records of 29
      patients (20 males and 9 females) who underwent double-door laminoplasty for
      cervical OPLL. T2-weighted MRI was performed preoperatively. To assess the high
      signal changes of the spinal cord, signal intensity was classified as grade 0
      (low signal, no changes), grade 1 (medium signal, mild changes), and grade 2
      (bright signal, pronounced changes). The following factors were analyzed for
      their relationship with surgical outcome, expressed as the Japanese Orthopedic
      Association (JOA) score recovery rate: pre- and postoperative C2-C7 range of
      motion (ROM), segmental ROM, C2-C7 lordotic angle, and spinal cord occupying
      ratio, as well as disease duration. RESULTS: Disease duration was significantly
      longer in patients with pronounced high-signal changes on preoperative MRI (P <
      0.05 for grade 2 vs. grade 1 or 0). The mean preoperative JOA score and JOA score
      recovery rate were significantly lower in patients with pronounced high-signal
      changes on preoperative MRI (P < 0.05 for grade 2 vs. grade 1 or 0).
      Preoperatively, segmental ROM was significantly smaller in patients with no MRI
      signal intensity changes (P < 0.05 for grade 0 vs. grade 1 or 2). Additionally,
      preoperative segmental ROM was negatively correlated with JOA score recovery rate
      (R=-0.470, P = 0.01) and positively correlated with high-signal changes on
      preoperative MRI (R = 0.460, P = 0.012). On multivariate analysis, preoperative
      segmental ROM was negatively associated with JOA score recovery rate (odds ratio,
      - 0.407; P = 0.046). CONCLUSION: Given its negative correlation with JOA score
      recovery rate and positive correlation with high-signal changes on preoperative
      MRI, higher preoperative segmental ROM may be associated with spinal cord damage
      due to repeated minor trauma, predicting poor surgical outcome of laminoplasty in
      cervical OPLL.

PMID- 30236638
TI  - Cervico-medullary compression ratio: A novel radiological parameter correlating
      with clinical severity in Chiari type 1 malformation.
AB  - OBJECTIVES: Chiari malformation type 1 (CM-1) is associated with cough headache,
      intracranial hypertension, cerebellar and spinal cord symptoms/signs. Herniated
      cerebellar tonsil length (HCTL) is widely used radiological parameter to
      determine the severity of CM-1, but with limited utility due to its weak
      correlation with some clinico-radiological findings. In this study, we aimed to
      evaluate a novel, practical parameter (cervico-medullary compression ratio;
      "CMCR") for its relationship with clinico-radiological findings in CM-1. PATIENTS
      AND METHODS: Thirty-five adult patients (17 F, 18 M) with CM-1 were included in
      this retrospective study. Head CT and craniospinal MR images were assessed. CMCR
      was calculated as the ratio of herniated cerebellar tonsil surface area to
      foramen magnum surface area, and HCTL was measured. These two parameters were
      correlated with clinical and radiological findings. RESULTS: The mean CMCR was
      0.60 +/- 0.15 and mean HCTL was 8.91 +/- 3.4 mm with no significant difference
      between gender and age groups for both parameters. For cough headache (0.64 +/-
      0.14 vs 0.52 +/- 0.15, p = 0.043) and syringomyelia (0.67 +/- 0.11 vs 0.56 +/-
      0.16, p = 0.039), only CMCR; for intracranial hypertension (CMCR: 0.64 +/- 0.14
      vs 0.55 +/- 0.16, p = 0.049; HCTL: 9.66 +/- 3.59 mm vs 7.79 +/- 3.03 mm; p =
      0.045) and cerebellar symptoms (CMCR: 0.65 +/- 0.14 vs 0.54 +/- 0.16, p = 0.048;
      HCTL: 10.4 +/- 3.5 mm vs 7.4 +/- 2.8 mm, p = 0.041), both CMCR and HTCL were
      significantly different between patients with and without respective findings.
      However, neither CMCR nor HTCL was different between patients with and without
      spinal cord symptoms and hydrocephalus. CONCLUSION: CMCR is a superior numerical
      parameter than HCTL for the assessment of clinical severity in CM-1 cases and
      needs further validation with larger studies.

PMID- 30236639
TI  - 30-day adverse outcomes, re-admissions and mortality following
      vertebroplasty/kyphoplasty.
AB  - OBJECTIVES: Despite vertebral fractures being a common occurrence in elderly
      osteoporotic individuals, literature remains scant with regards to 30-day
      outcomes following vertebral augmentation for these injuries. We studied a
      national database of elderly osteoporotic patients who underwent vertebroplasty
      and kyphoplasty. PATIENTS AND METHODS: The 2012-2014 ACS-NSQIP database was
      queried using CPT codes for vertebroplasty (22520, 22521 and 22522) and
      kyphoplasty (22523, 22524 and 22525). Patients undergoing concurrent spinal
      fusion and/or laminectomies/laminotomies/laminoplasties were removed from the
      study. Patients with missing data were also excluded from the study. RESULTS:
      Following inclusion/exclusion criteria, a total of 2433 patients were included in
      the study out of which 242(9.9%) underwent vertebroplasty and 2191(90.1%)
      underwent kyphoplasty. Following adjusted analysis, having a dependent functional
      health status pre-operatively (OR 1.78; p = 0.010), pre-operative sepsis/SIRS (OR
      2.52; p = 0.009), history of COPD (OR 1.62; p = 0.025), disseminated cancer (OR
      1.94; p = 0.028), pre-operative wound infection (OR 3.47; p = 0.003) and
      inpatient admission status (OR 3.22; p < 0.001) were independent predictors of
      having any complication within 30-days of the procedure. Significant independent
      risk factors for 30-day mortality were functional health status prior to surgery
      (OR 2.92; p = 0.002), pre-operative dialysis use (OR 11.74; p = 0.003),
      Disseminated cancer (OR 7.09; p < 0.001), chronic steroid use (OR 3.59; p <
      0.001), and inpatient admission status (OR 4.95; p < 0.001). CONCLUSION:
      Vertebroplasty/Kyphoplasty is associated with significant adverse outcomes.
      Providers can utilize these data to better pre-operatively filter high-risk
      patients and tailor an appropriate peri-operative medical optimization program to
      enhance care to lower the risk of complications, readmissions and mortality from
      this procedure.

PMID- 30236640
TI  - Comorbid social anxiety disorder in patients with alcohol use disorder: A
      systematic review.
AB  - INTRODUCTION: Lifetime prevalence of social anxiety disorder (SAD) among patients
      with alcohol dependence is around 11%. However, no systematic review has assessed
      the effect of comorbid SAD on the clinical outcomes of patients with alcohol use
      disorder (AUD). OBJECTIVES: We aimed to compare clinical outcomes, such as
      alcohol relapse, suicide attempts, treatment response, readmissions, psychiatric
      comorbidities, and treatment compliance between patients with AUD and comorbid
      SAD versus patients with AUD without SAD. METHODS: We carried out a systematic
      review by searching PubMed for articles published between January 1, 1960 and May
      6, 2018. Inclusion criteria were met if a study reported a dichotomous sample of
      adult patients with AUD and SAD compared to patients with AUD without SAD. Review
      articles and preclinical studies were excluded. From the eligible studies, we
      extracted outcomes of interest, such as alcohol relapse, suicidal thoughts,
      suicide plan and attempts, treatment response, readmissions, psychiatric
      comorbidities, and treatment compliance. RESULTS: Patients with both AUD and SAD
      have a higher prevalence of psychiatric comorbidities, mainly major depressive
      disorder (MDD), and depressive symptoms. In addition, they have poor treatment
      compliance. Conversely, the impact of comorbid SAD on alcohol relapse is
      controversial and current studies have yielded mixed results. Only one study
      assessed the impact of comorbid SAD on treatment response and showed no
      association. Furthermore, one study assessed suicidality and found higher rates
      of suicidal thoughts, suicide plans and attempts in patients with AUD and SAD.
      CONCLUSION: The present systematic review shows that it is important to screen
      for other psychiatric comorbidities (especially MDD), suicidality, and improve
      treatment adherence in patients with AUD and comorbid SAD. Future prospective
      studies should clarify the impact of comorbid SAD.

PMID- 30236641
TI  - The IMPORT LOW Trial: Collaborative Research Accelerates Practice Change in
      Breast Radiotherapy.

PMID- 30236642
TI  - Digital breast tomosynthesis: Image acquisition principles and artifacts.
AB  - Digital breast tomosynthesis (DBT) is a new technology that is being used more
      frequently for both breast cancer screening and diagnostic purposes and its
      utilization is likely to continue to increase over time. The major benefit of
      tomosynthesis over 2D-mammography is that it allows radiologists to view breast
      tissue using a three-dimensional dataset and improves diagnostic accuracy by
      facilitating differentiation of potentially malignant lesions from overlap of
      normal tissue. In addition, image processing techniques allow reconstruction of
      two dimensional synthesized mammograms (SM) from DBT data, which eliminates the
      need for acquiring two dimensional full field digital mammography (FFDM) in
      addition to tomosynthesis and thereby reduces the radiation dose. DBT systems
      incorporate a moveable x-ray tube, which moves in a prescribed way over a limited
      angular range to obtain three-dimensional data of patients' breasts, and utilize
      reconstruction algorithms. The limited angular range for DBT leads to incomplete
      sampling of the object, and a movable x-ray tube prolongs the imaging time, both
      of which make DBT and SM susceptible to artifacts. Understanding the etiology of
      these artifacts should help radiologists in reducing the number of artifacts and
      in differentiating a true finding from one related to an artifact, thus
      potentially decreasing recall rates and false positive rates. This is becoming
      especially important with increased incorporation of DBT in practices around the
      world. The goal of this article is to review the physics principles behind DBT
      systems and use these principles to explain the origin of artifacts that can
      limit diagnostic evaluation.

PMID- 30236643
TI  - The effect of worrying on intolerance of uncertainty and positive and negative
      beliefs about worry.
AB  - BACKGROUND AND OBJECTIVES: The effect of a worry manipulation on the clinical
      constructs intolerance of uncertainty (IU), negative beliefs about the
      consequences of worry (NCOW), positive beliefs about the consequences of worry
      (PCOW), in addition to the emotions anxiety and sadness, was examined. METHODS: A
      non-clinical sample was split into two groups, a worry group (n = 29), who were
      asked to generate 20 potential worries about a hypothetical scenario, and a
      control group (n = 28), who were asked to generate 2 potential worries about the
      same scenario. Subsequently, participants were asked to complete measures of IU,
      NCOW, PCOW, sadness and anxiety. RESULTS: The worry group scored significantly
      higher than the control group on measures of IU, NCOW and PCOW but not on
      measures of sadness and anxiety. LIMITATIONS: Possible limitations of the current
      study include the use of a student sample and the use of a hypothetical worry
      scenario. CONCLUSIONS: The results suggest that engaging in worry can increase
      scores on measures of the beliefs and thought patterns often used to causally
      explain worry. The results are in line with recent research showing
      bidirectionality between anxiety related symptoms and their associated clinical
      constructs, and are consistent with an approach which sees anxiety symptoms as
      part of an evolved integrated threat management system that alerts the individual
      to threats to goals or challenges, and coordinates cognitive, behavioral, and
      affective reactions to enable effective responding to these threats and
      challenges.

PMID- 30236644
TI  - Designing an ADME liquid formulation with matching exposures to an amorphous
      dosage form.
AB  - Amorphous Solid Dispersion (ASD) based formulations have been frequently used to
      improve the bioavailability of poorly water soluble drugs, however, common
      processes to produce ASDs are not feasible for Absorption, Distribution,
      Metabolism and Excretion (ADME) studies with radio-labeled Active Pharmaceutical
      Ingredients (API) due to the complications associated with radioactive material
      handling. Liquid formulations are routinely used to support the ADME studies,
      though bridging the bioperformance between a liquid formulation to the amorphous
      dosage form for poorly soluble compounds has not been well studied, and can be
      challenging due to the potentially rapid in vitro and in vivo recrystallization
      and precipitation. Here we report the development of a fit for purpose liquid
      formulation that could accommodate the radioactive API and provide comparable
      bioavailability relative to the amorphous formulation without the need for dose
      adjustment. A number of formulation approaches were explored and the prototype
      formulations were evaluated by dissolution and preclinical pharmacokinetic
      studies. A PolyEthylene Glycol 400 (PEG 400) based solution formulation
      impregnated with a polymer, HydroxyPropyl MethylCellulose Acetate Succinate-L
      (HPMCAS-L), was identified as the lead formulation. It was found that the
      bioavailability of the formulation can be compromised by the presence of
      undissolved crystalline seeds, and the inclusion of HPMCAS-L can mitigate this
      effect, as well as potentially facilitate the nanoparticle formation. During the
      study, it is also noted that although dissolution test is instrumental in the
      formulation development, the in vitro study over predicted the extent of in vivo
      precipitation for PEG 400 formulation containing no crystalline seeds.

PMID- 30236645
TI  - Optimized acriflavine-loaded lipid nanocapsules as a safe and effective delivery
      system to treat breast cancer.
AB  - Acriflavine (ACF) hydrochloride is currently repurposed as multimodal drug,
      inhibiting hypoxia-inducible factors (HIF) pathways and exerting cytotoxic
      properties. The aim of this study was to encapsulate ACF in reverse micelles and
      to incorporate this suspension in lipid nanocapsules (LNC). Designs of
      experiments were used to work under quality by design conditions. LNC were
      formulated using a phase-inversion temperature method, leading to an
      encapsulation efficiency around 80%. In vitro, the encapsulated drug presented
      similar cytotoxic activity and decrease in HIF activity in 4T1 cells compared to
      the free drug. In vivo, ACF-loaded nanoparticles (ACF dose of 5 mg/kg)
      demonstrated a higher antitumor efficacy compared to free ACF on an orthotopic
      model of murine breast cancer (4T1 cells). Moreover, the use of LNC allowed to
      drastically decrease the number of administrations compared to the free drug (2
      versus 12 injections), suppressing the ACF-induced toxicity.

PMID- 30236646
TI  - Investigating the effects of amphipathic gastrointestinal compounds on the
      solution behaviour of salt and free base forms of clofazimine: An in vitro
      evaluation.
AB  - Interactions between hydrophobic drugs and endogenous gastrointestinal substances
      have the potential to manipulate drug concentration in the human gastrointestinal
      system, and thus likely play an important role in determining the rate of
      absorption for hydrophobic drugs. The effects of phospholipids, bile salts and
      digestive proteins on the solution behaviour of clofazimine in biorelevant media
      was demonstrated here using dissolution experiments and solid state analytical
      techniques. Clofazimine is a hydrophobic, anti-mycobacterial agent with virtually
      no detectable water solubility in its free base form. Salt forms of the drug
      offer improved aqueous solubility but are unstable in solutions at low pH (pH
      1.6) or high pH (pH 6.5). At low pH and high chloride ion concentrations, CFZ in
      solution experiences a high driving force to crystallize from solution as a
      hydrochloride salt, which is insoluble, while at high pH CFZ does not dissolve to
      any extent. In this study, it is demonstrated that amphipathic compounds present
      in the gastric and intestinal systems can overcome the instability experienced by
      CFZ at these pH values. This is done by encapsulation of the hydrophobic drug in
      mixed bile salt phospholipid micelles in both the gastric and intestinal fluid,
      and by the drug actively binding with the digestive enzyme pepsin in the gastric
      system. Pepsin binds and solubilises the drug at even relatively low
      concentration (0.1 mg/mL). When pepsin concentration is increased in the gastric
      media, a corresponding increase in the solution stability of CFZ is observed.

PMID- 30236647
TI  - Vesicular systems employing natural substances as promising drug candidates for
      MMP inhibition in glioblastoma: A nanotechnological approach.
AB  - Glioblastoma multiforme (GBM), one of the most lethal Brain tumors, characterized
      by its high invasive nature and increased mortality rates forms a major
      bottleneck in transport of therapeutics across the Blood Brain Barrier (BBB).
      Matrix metalloproteinases (MMPs) are classified as enzymes, which are found to be
      up regulated in the Glioma tumor microenvironment and thus can be considered as a
      target for inhibition for curbing GBM. Many chemotherapeutics and techniques have
      been employed for inhibiting MMPs till now but all of them failed miserably and
      were withdrawn in clinical trials due to their inability in restricting the tumor
      growth or increasing the overall survival rates. Thus, the quest for finding the
      suitable MMP inhibitor is still on and there is a critical need for
      identification of novel compounds which can alter the BBB permeability, restrain
      tumor growth and prevent tumor recurrence. Currently, naturally derived
      substances are gaining widespread attention as tumor inhibitors and many studies
      have been reported by far highlighting their importance in restricting MMP
      expression thus serving as chemotherapeutics for cancer due to their minimal
      toxicity. These substances may serve as probable candidates for inhibiting MMP
      expression in GBM. However, targeting and delivering the inhibitor to its target
      site is an issue that needs to be overcome in order to attain maximum specificity
      and sustained release. The birth of nanotechnology served as a boon in delivering
      drugs to the most complicated areas thus paving way for Nano drug delivery. An
      efficient Nano carrier with ability to cross the BBB and competently kill the
      Glioma cells forms the prerequisite for GBM chemotherapy. Vesicular drug delivery
      systems are one such class of carriers, which have the capacity to release the
      drug at a predetermined rate at the target site thus minimizing any undesirable
      side effects. Exploiting vesicular systems as promising Nano drug carriers to
      formulate naturally derived substances, that can bypass the BBB and act as an
      inhibitor against MMPs in GBM is the main theme of this review.

PMID- 30236648
TI  - Freeze drying of polyelectrolyte complex nanoparticles: Effect of nanoparticle
      composition and cryoprotectant selection.
AB  - This work investigates the impact of nanoparticle (NP) composition and
      effectiveness of cryo-/lyo-protectants in a freeze drying process, which was
      employed to convert liquid dispersions of polyelectrolyte complex (PEC) NPs into
      completely redispersible powders. PEC NPs, with and without peptide, were
      produced by complex coacervation. The cryo-/lyo-protectants investigated were
      mannitol, trehalose (TRE) and poly(ethylene glycol) (PEG). The solid state of
      lyophilised powders was studied by thermal analysis and X-ray diffraction.
      Cytotoxicity studies were done by MTS assay and flow cytometry. The presence of a
      cryoprotectant was essential to achieve a successful powder reconstitution. The
      concentration of TRE was optimised for each type of PEC NPs. Protamine- and
      hyaluronate-based NPs reconstituted better than chitosan- and chondroitin
      sulphate-based NPs, respectively. PEG polymers were found to be more effective
      cryoprotectants than TRE and best results were achieved using co-freeze drying of
      NPs with TRE and PEG. These ternary NPs/TRE/PEG samples were crystalline, with
      expected better storage stability. PEG polymers were well tolerated by Caco-2
      cells, with the exception of linear PEG 10 kDa. This work shows that, as regards
      the formulation design and maximising NP loading in the dried product,
      optimisation of the cryoprotectant type and content is needed as it is highly
      dependent not only on the type of polyelectrolyte pair in the PEC, but also the
      polyions ratio.

PMID- 30236649
TI  - Granule formation and structure from single drop impact on heterogeneous powder
      beds.
AB  - Single drop impact of liquid on a static powder bed was studied to investigate
      the granule formation mechanism, droplet penetration time, as well as the
      characterization of granules (morphology, surface structure and internal
      structure). Water was used as the liquid and two pharmaceutical powders,
      microcrystalline cellulose (MCC) and acetaminophen (APAP), were mixed to make
      heterogeneous powder beds. The complete drop impact and penetration was recorded
      by a high speed camera. Two granule formation mechanisms that have been
      identified previously occurred: Spreading and Tunneling. Spreading occurred for
      mixtures with an APAP amount of less than 20%, while Tunneling started to occur
      when the APAP amount increased above 20%. With an increase of APAP concentration,
      the mean particle size decreased, drop penetration time increased, and the
      granules formed became smaller in size, which was in good agreement with previous
      literature. The granule morphology, surface structure, and internal structure
      were characterized by a prism method with image analysis, scanning electron
      microscopy (SEM), and X-ray microtomography, respectively. The Spreading
      mechanism produced flat disks with a porous internal structure, while the
      Tunneling mechanism produced round granules with a dense internal structure.
      There is a clear trend of decreasing porosity and increasing roundness of
      granules made from heterogeneous mixtures within the transition from Spreading to
      Tunneling. It is believed that the mean particle size of the powder bed and the
      powder-liquid contact angle are the predominant factors in influencing the
      formation mechanism, drop penetration time, and granule properties.

PMID- 30236650
TI  - The utility of a normal tear osmolarity test in patients presenting with dry eye
      disease like symptoms: A prospective analysis.
AB  - OBJECTIVE: To explore the diagnostic utility of normal tear osmolarity in
      patients with symptoms suggestive of dry eye disease (DED). METHODS: Prospective
      observational cohort study of 100 patients that underwent tear osmolarity testing
      (TearLabTM) if they endorsed one or more symptoms of potential DED. Patients were
      included for the study if they had a normal tear osmolarity test (value <308
      mOsm/L in each eye, and an inter-eye difference <8 mOsm/L). The main outcome
      measure was the presence of any alternate diagnosis to explain the patient's
      symptoms. Results were recorded and descriptive and univariate statistics were
      employed. RESULTS: Mean tear osmolarity was 293.40 mOsms/L (+/-6.82), with a mean
      absolute difference of 2.85 mOsms/L (+/-1.98) between the eyes. A possible
      alternate diagnosis was established in 89% of patients with normal tear
      osmolarity testing. The most frequent diagnoses included anterior blepharitis
      (26%) and allergic conjunctivitis (21%). CONCLUSIONS: Common symptoms of DED
      overlap significantly with a wide variety of other ocular surface diseases, and a
      normal tear osmolarity test should increase clinical suspicion for alternate
      causes of those symptoms. Anterior blepharitis and allergic conjunctivitis were
      the most common diagnoses made in symptomatic patients with normal tear
      osmolarity who may have otherwise been misdiagnosed and treated for DED.

PMID- 30236651
TI  - Diagnosis, treatment and long-term outcome of autoimmune pancreatitis in Sweden.
AB  - INTRODUCTION: Autoimmune pancreatitis (AIP) is a pancreatic inflammatory process
      characterized by a strong inflammatory cell infiltration and two
      histopathologically distinct subtypes: type 1 and type 2. Diagnosis is often
      challenging and requires a combination of clinical, laboratory and imaging data.
      AIP can mimic pancreatic tumours leading to unnecessary resections if not
      correctly diagnosed. Short- and long-term outcomes of AIP have been poorly
      investigated so far and no large series have been previously reported from
      Sweden. METHODS: A single-centre, retrospective, cohort study of patients with
      histologically confirmed or highly probable diagnosis of AIP according to ICDC
      criteria. Demographic, clinical and radiological characteristics, type of
      treatment and its outcomes were collected and analysed. RESULTS: Seventy-one
      patients with AIP (87% with type 1), were evaluated at Karolinska University
      Hospital between 2004 and 2018; 49% males, mean age 49 years (range 44-53). Among
      them, 28% were histologically confirmed, 35% presented with jaundice, 22% with
      acute pancreatitis, 39% had non-specific symptoms such as weight loss or
      abdominal pain, 84% showed other organ involvement (OOI). Radiologically, 76%
      showed a focal pancreatic enlargement, 27% diffuse enlargement, 27% signs of
      acute pancreatitis and 10% of chronic pancreatitis. Overall, 58 patients (81%)
      underwent treatment with different medications: 46 (79%) cortisone, 7 (12%)
      azathioprine, 5 (8%) other immunosuppressive drugs. Twenty-six (36%) underwent
      biliary stenting and 12 (16%) were given surgery. In total, 47% of patients
      developed pancreatic exocrine insufficiency (PEI), of whom 76% had a severe form
      (faecal elastase-1 < 100 MUg/g) and 21% of patients developed diabetes mellitus
      (pancreatic endocrine insufficiency), of whom 73% required insulin. CONCLUSIONS:
      AIP is a challenging disease for diagnosis and treatment. Cortisone treatment is
      generally successful and provides clinical remission in the large majority of
      patients (>90%). In the further course of the disease, a considerable number of
      patients develop PEI and diabetes. Only one-quarter of patients exhibit on
      imaging the characteristic "sausage-like" pancreas (diffuse enlargement),
      approximately three-quarters had a focal mass that could be misdiagnosed as
      pancreatic malignancy.

PMID- 30236652
TI  - Development of four PCR-based methods to differentiate tilefish species
      (Branchiostegus japonicus and B. albus).
AB  - The red tilefish (Branchiostegus japonicus) is an important ingredient and
      fishery resource in South Korea. Branchiostegus japonicus-specific and tilefish
      primer sets were designed, and four PCR-based methods were developed to
      differentiate B. japonicus and B. albus species. The specificity of the
      conventional and quantitative real-time PCR (qPCR) developed was confirmed using
      twenty species, showing no cross-activity, and the limit of detection was 0.1
      0.001 ng/uL. Their accuracy was validated using a forensically informative
      nucleotide sequencing method on forty-seven red tilefish products. These two
      methods were further improved to develop direct triplex PCR and ultra-fast qPCR
      for the on-site food analysis, which could complete the entire analytical
      procedure within either 90 or 30 min, while maintaining the same accuracy.
      Therefore, these four PCR methods can be efficiently customized in various
      analytical areas and conditions, including field analysis, rapid screening,
      quality control, and labeling compliance, required by food manufacturing industry
      and regulatory authorities.

PMID- 30236653
TI  - Hierarchical structure and physicochemical properties of highland barley starch
      following heat moisture treatment.
AB  - Herein, we concern the multi-scale structure and properties (digestibility and
      pasting) of highland barley starch following heat moisture treatment (HMT). With
      the moisture content (MC) rose, HMT reduced the molecular weight (molar mass) but
      increased the amylose content and the V-type polymorph. When the MC was lower
      than 25%, a higher MC resulted in increases in the long- (crystallites) and short
      range orders (double helices, etc.); nonetheless, a further elevated MC (i.e.,
      30%) tended to reduce the amounts of these ordered structures. Also, the SAXS
      results reveal that the lamellar structure could be gradually vanished by the
      increased MC. These structural changes on multiple scales transformed part of
      rapidly digestible starch into the slowly digestible and/or resistant forms,
      accompanied by higher pasting temperature and lower paste viscosity. Hence,
      highland barley starch following HMT can serve as a food ingredient with reduced
      digestion rate and paste viscosity.

PMID- 30236654
TI  - Pulsed light inactivation of polygalacturonase.
AB  - Pulsed light is a non-thermal technology capable to inactivate enzymes. This
      study investigated the effect of pulsed light on the activity of
      polygalacturonase, and on the structure of the enzyme by means of fluorescence
      emission spectra, free sulphydryl detection and analysis of changes in parameter
      A and phase-diagram. The results showed that pulsed light is able to inactivate
      polygalacturonase in buffer, with >90% reduction of enzyme activity after
      applying 128 J/cm2 and a first-order kinetic constant of 0.0426 cm2/J under the
      experimental conditions. The free sulfhydryl detection revealed the rupture of
      sulfhydryl bridges. Fluorescence spectra analysis showed that the tertiary
      structure of polygalacturonase was changed. Phase diagram analysis shows the
      existence of only two populated states. It is suggested that the inactivation of
      polygalacturonase by pulsed light is an all-or-none process where disulfide
      bridges are broken and the enzyme is unfolded.

PMID- 30236656
TI  - Surfactant type affects the washing effect of cinnamon leaf essential oil
      emulsion on kale leaves.
AB  - With increasing foodborne illness associated with fresh-cut produce, a chemical
      sanitizer to substitute chlorine is needed in the food industry. This study
      examined the washing effect of cinnamon leaf essential oil (CL-EO) emulsions on
      fresh-cut produce according to the ionic properties of surfactants. Washing
      effect of CL-EO emulsion (CLC) with cetylpyridinium chloride was the highest
      among all treatments on kale leaves. After CLC treatment, 1.83 and 1.54 log
      reductions against Listeria monocytogenes and Escherichia coli O157:H7 were
      achieved, respectively, compared to washing with distilled water, and had about
      0.6 log-reductions higher than NaOCl treatment. CL-EO droplets in CLC had a
      positive zeta-potential (+55 mV) compared to other emulsions. These results
      indicate that ionic properties of surfactants are very important in the washing
      effect of CL-EO emulsion. Additionally, CLC treatment did not affect the quality
      of kale leaves during storage. Therefore, CLC can be an effective chemical
      sanitizer for washing kale leaves.

PMID- 30236655
TI  - Hydrothermal stability of phenolic extracts of brown rice.
AB  - The phenolics were extracted and purified from brown rice and twenty-seven
      compounds were identified, including six phenolic acids, four phenolic acid
      glycosides, and eight flavonoid glycosides. Afterwards, the hydrothermal
      stability of phenolic extracts of brown rice was investigated after treatment at
      60, 80, or 100  degrees C for 120 min. After hydrothermal treatment, ferulic
      acid, p-coumaric acid and free glucose were increased, while the phenolic
      glycosides were decreased. In addition, the total phenolic and total flavonoid
      content were decreased by 5.7%-9.2% and 3.5%-5.8% after initial 30 min, and then
      they were slightly recovered after treatment for 120 min. Consequently, there was
      a slight reduction (<10%) in the total antioxidant activity of the phenolic
      extracts after hydrothermal treatment. These results suggest that hydrothermal
      treatment of phenolic extracts of brown rice made some phenolic glycosides
      deglycosylated, but does not lead to a large reduction in their overall
      antioxidant activity.

PMID- 30236657
TI  - Effect of different processing conditions on proximate composition, anti
      oxidants, anti-nutrients and amino acid profile of grain sorghum.
AB  - The effect of different processing conditions (B: boiling; F: LAB fermentation;
      FS: fermentation and steaming; FSF: fermentation, steaming, flaking) of whole
      grain sorghum on the proximate composition, antioxidants, anti-nutrients, and
      amino acids (AAs) was evaluated. A marginal increase in the protein content and a
      decrease in the fat content was observed in the F-sample. Total phenolics reduced
      by 28%; DPPH scavenging activity and CUPRAC activity increased by 1.4 and 6
      times, respectively during fermentation. Tannin content reduced by 30-39%, for
      the F, FS and FSF samples; highest reduction in trypsin inhibitory activity (58%)
      was observed in the FS-sample. Total AAs increased by 2.9 folds in FSF samples.
      Grain sorghum contained mostly hydrophobic AAs (30-34%). The ratio of Essential
      amino acid to total amino acid and predicted protein efficiency ratio were
      highest in the F-sample, whereas predicted biological value of the FSF was 3
      times than that of the control.

PMID- 30236659
TI  - Effect of radio frequency heat treatment on protein profile and functional
      properties of maize grain.
AB  - The study was aimed at investigating the effect of radio frequency (RF) heating
      at different temperatures on the protein profile and functional properties of
      maize grains. Maize grains with 14% moisture content exposed to the radio
      frequency energy at 300 W for different temperatures 50, 55 and 60  degrees C,
      respectively. The results indicated that radio frequency heating had no effect on
      the protein profile of maize. The molecular weight distribution of protein
      remained in the range of 20-25 kDa after RF heating. On the other hand, the
      functional properties in term of oil holding capacity and emulsifying properties
      of maize were improved after RF heating. According to these finding, it can be
      concluded that radio frequency heating improves the functional properties of
      maize flour. Thus, RF may provide a potential as an effective emerging technology
      for improving the quality characteristics of maize grains.

PMID- 30236658
TI  - Dephosphorylation of caseins in milk protein concentrate alters their
      interactions with sodium hexametaphosphate.
AB  - This study investigated the effects of dephosphorylation and sodium
      hexametaphosphate (SHMP) salt addition on the viscosity of milk protein
      concentrate (MPC) solutions. Dephosphorylation (DP) of casein was performed using
      bovine alkaline phosphatase. Nuclear magnetic resonance (NMR) spectra showed that
      dephosphorylation depleted the casein-bound phosphate region (CNP). SHMP addition
      (5 mM) had no impact on the 31P NMR spectra of DP-MPC; addition of 5 mM SHMP to
      control MPC (C-MPC) resulted in a shift in peaks associated with the CNP region,
      possibly caused by SHMP sequestering calcium, leading to swelling of micelles. DP
      MPC exhibited a lower viscosity compared to C-MPC, with SHMP addition at 12.5 and
      25 mM causing gelation of C-MPC and DP-MPC solutions. This work confirmed the
      role that phosphate residues have in maintaining micelle structural stability and
      provides new insights into controlling viscosity of MPC solutions.

PMID- 30236660
TI  - Hepatoprotective activity of Ganoderma lucidum triterpenoids in alcohol-induced
      liver injury in mice, an iTRAQ-based proteomic analysis.
AB  - The hepatoprotective activity of ethanol extract of Ganoderma lucidum (GLE) in
      alcohol-induced liver injury in mice was investigated. HPLC coupled with photo
      diode array detector and electrospray ionization-mass spectrometry was used to
      analyze the major triterpenoids in GLE. The effects of GLE on hepatoprotection
      were evaluated through histopathology and biochemical analysis of serum enzymes.
      We used isobaric tag for relative and absolute quantitation (iTRAQ) coupled with
      tandem mass spectrometry to identify differentially expressed liver proteome in
      mice. There were more than 4000 differentially expressed proteins; 40 proteins
      with the most significant changed proteins were applied for further
      bioinformatics analysis. Expression levels of cytochrome P450 2E1 and alcohol
      dehydrogenase 1, proteins that are closely associated with these processes, were
      validated by western blotting. Triterpenoids, major components of GLE, protected
      alcohol-induced liver injury through inhibiting lipid peroxidation, elevating
      activity of antioxidant enzymes, and suppressing apoptotic cell death and immune
      inflammatory response.

PMID- 30236661
TI  - Gluten-free flours from cereals, pseudocereals and legumes: Phenolic fingerprints
      and in vitro antioxidant properties.
AB  - The interest in gluten-free (GF) products increases together with the increase in
      gluten-sensitive people. However, GF foods might have decreased nutritional
      quality as compared to the gluten containing counterparts. In this work, an
      investigation of the phenolic and antioxidant profile in 18 GF flours belonging
      to legumes, cereals and pseudocereals was achieved. Significant differences could
      be observed across samples. Total phenolic content was highest in violet rice
      flours, whereas total anthocyanins were highest in violet, nerone, and black rice
      flours. FRAP and ORAC antioxidant activities were correlated to phenolic contents
      and found to be higher in violet rice flours. Metabolomics highlighted a wide
      diversity in phenolics, with flavonoids (197 compounds ascribable to
      anthocyanins, flavones, flavanones, isoflavonoids, flavonols, and flavanols),
      phenolic acids (74 compounds belonging to hydroxycinnamics, hydroxybenzoics, and
      hydroxyphenylacetics), and tyrosol derivatives the most represented. Finally,
      OPLS-DA multivariate statistics outlined flavonoids, furofurans and phenolic
      acids as the most discriminant phenolics.

PMID- 30236662
TI  - Effect of various hydrocolloids on the physical and fermentation properties of
      dough.
AB  - Sixteen hydrocolloids (12 carbohydrate-origin and 4 protein-origin hydrocolloids)
      at several concentrations were added to dough and their rheological, pasting and
      fermentation properties were studied. We found that 0.2-1% guar gum (GG) and
      locust bean gum (LBG) resulted in more strengthened doughs. But 0.2-1% pectin and
      konjac glucomannan (KGM) yielded weaker dough. The chemical interactions study
      suggested that pectin and KGM induced highest content of chemical bonds. In the
      fermentation studies, it was found that pectin, GG and agaric gum (AG) had
      positive effects, resulting in higher stability of dough pore space and gas
      retention. All protein hydrocolloids exhibited a negative effect on dough
      quality. Overall, polysaccharide based hydrocolloids with linear chain and higher
      viscosity have a remarkable effect on the enhancing gluten network. The
      interaction between hydrocolloids and gluten proteins was also crucial for dough
      properties, as exceptionally strong interactions caused disaggregation and
      instability of gluten network.

PMID- 30236663
TI  - Effects of inoculating autochthonous starter cultures on N-nitrosodimethylamine
      and its precursors formation during fermentation of Chinese traditional fermented
      fish.
AB  - This study investigated the effects of Lactobacillus plantarum 120, Saccharomyces
      cerevisiae 2018 and Staphylococcus xylosus 135 inoculation on N
      nitrosodimethylamine (NDMA) and its precursors formation, and on microbiological
      characteristics of Chinese traditional fermented fish products (CTFPs). The
      results indicated that three strains could directly degrade NDMA in culture
      broth, and the highest degradation rate was observed in L. plantarum 120. The
      lactic acid bacteria counts in samples inoculated with L. plantarum 120 and mixed
      starter cultures were significantly (P < 0.05) higher than the others during the
      initial and middle fermentation stages (<=3 weeks). The final contents of total
      volatile base nitrogen, trimethylamine, dimethylamine, nitrite and NDMA in
      inoculated samples were significantly (P < 0.05) lower than those in spontaneous
      fermentation samples. According to these results, the inoculation with
      autochthonous starter cultures was a promising method to inhibit the NDMA and its
      precursors accumulation in CTFPs during fermentation process.

PMID- 30236664
TI  - Anthocyanins accumulation and molecular analysis of correlated genes by
      metabolome and transcriptome in green and purple asparaguses (Asparagus
      officinalis, L.).
AB  - Asparagus (A. officinalis L.) is a highly nutrition vegetable crop. Here, three
      purple asparagus cultivars, namely, Jing Zi-2, Purple Passion and Pacific Purple,
      and one green cultivar, namely, Jing Lv-1 were studied. At least 16 kinds of
      anthocyanins were identified in purple and green cultivars, and peonidin,
      cyanidin and their glycoside derivatives were found to be the major anthocyanins.
      Transcriptome data showed that most anthocyanin biosynthetic genes and at least 5
      kinds of transcription factors were significantly differentially expressed
      significantly between the green and purple cultivars. Dark-treated experiments
      revealed that anthocyanins are not produced in the absence of light, and both the
      anthocyanin biosynthetic and regulatory genes were down-regulated greatly in the
      dark, implying that anthocyanins accumulation in asparagus is light-dependent.
      Overall, the results of this study provide useful information for understanding
      anthocyanin accumulation and the molecular mechanism of anthocyanin biosynthesis
      in asparagus.

PMID- 30236665
TI  - Starch granules as active guest molecules or microorganism delivery systems.
AB  - Starch granules contain an internal channel structure that can be used to
      encapsulate and deliver active ingredients such as nutrients, drugs, chemicals
      and microorganisms. Nature creates a broad range of starch granule sizes and
      compositions in different plants and this range of encapsulation matrices
      provides a great deal of commercial opportunity. Starch granules can be utilised
      for encapsulation in their native form or treated with amylases/amyloglucosidase
      to facilitate the entry of active ingredients into the granules. Interactions
      within the granules can be relatively passive or more structured in the form of
      complexes (such as amylose-lipid complexes). This mini-review evaluates this
      application of starch and potential commercial product opportunities.

PMID- 30236666
TI  - Enhanced accumulation of gamma-aminobutyric acid in rice bran using anaerobic
      incubation with various additives.
AB  - An anaerobic incubation for the enzymatic production of gamma-aminobutyric acid
      (GABA) in rice bran with the addition of glutamate, hydrolyzed wheat protein
      (HWP), yeast extract (YE) and pyridoxal-5-phosphate (PLP) was investigated. Rice
      bran was moistened (30% moisture content) with an electrolyzed oxidizing water
      and anaerobically incubated under nitrogen at 40  degrees C for 8 h. The
      incubation activated the glutamate decarboxylase (GAD) in rice bran and increased
      the GABA content from 10.7 to 171.5 mg/100 g. The addition of glutamate and
      protein hydrolysates further amplified the GABA content in the treated rice bran:
      974.9, 487.4, and 372.8 mg/100 g, with 2.25% glutamate, 6% HWP, and 8% YE,
      respectively. Furthermore, addition of PLP (1.48 mg/100 g) as a coenzyme for GAD,
      together with 2.25% glutamate addition, could raise the GABA accumulation in rice
      bran to 2242 mg/100 g. Other amino acids in rice bran were changed in their
      composition by the anaerobic treatment.

PMID- 30236667
TI  - Rheological and quality characteristics of composite gluten-free dough and
      biscuits supplemented with fermented and unfermented Agaricus bisporus
      polysaccharide flour.
AB  - In this study, functional, rheological and physicochemical characteristics were
      carried out for composite gluten-free (CGF) flours, dough and biscuits,
      respectively fortified with fermented and unfermented Agaricus bisporus
      polysaccharide (FABP and UABP) flours. Addition of both FABP flour and UABP flour
      improved functional properties, while addition of FABP flour decreased viscosity
      property. Incorporation of both polysaccharide flours in CGF biscuit dough
      revealed a significant increase in rheological moduli (G' and G") and a decrease
      in tan (delta). Supplementation of UABP flour increased thickness, whereas
      supplementation of FABP flour increased diameter and spread ratio. All CGF
      biscuit formulations exhibited lower fracture strength and hardness compared to
      the control. Furthermore, both UABP flour and FABP flour formulation (F3)
      contained the highest nutrients in terms of protein, dietary fibers, amino acids
      and minerals among the CGF biscuit formulations. The sensory evaluation result
      showed that FABP flour formulation (F1) and UABP flour F1 were most acceptable.

PMID- 30236668
TI  - The effects of EGCG on the mechanical, bioactivities, cross-linking and release
      properties of gelatin film.
AB  - The effects of (-)-epigallocatechin gallate (EGCG) on the mechanical,
      antioxidative, antimicrobial, cross-linking and release properties of gelatin
      film were evaluated. The biofilm exhibited excellent antioxidant and
      antibacterial activities against Staphylococcus aureus and Escherichia coli in
      the presence of EGCG at more than 3%. With the increasing content of EGCG (1%
      5%), higher denaturation temperature (66.5-84.6  degrees C) and bloom strength
      (609.3-1114.7 g) and denser microstructure suggested the existence of cross
      linking bonds in the biofilm. The infrared spectroscopy, protein pattern and
      release property of EGCG showed that hydrogen bonds were the main driving force
      for cross-linking of the biofilm. The release of EGCG from the biofilm system was
      described and two compounds were cross-linked via hydrogen bonds. Thus, this
      study confirmed the improvement on mechanical, bioactivities and release
      properties of the biofilm was most likely due to the interactions between gelatin
      and EGCG.

PMID- 30236669
TI  - Volatile fingerprints and biomarkers of three representative kiwifruit cultivars
      obtained by headspace solid-phase microextraction gas chromatography mass
      spectrometry and chemometrics.
AB  - Volatile aroma of kiwifruit is a mixture of complicated and time-dependent
      compounds, and thereby the study of these compounds required distinguished
      analytical techniques as well as robust data analysis techniques. In this work,
      we report on the volatile fingerprints and biomarkers of three representative
      kiwifruit cultivars with commercial importance using headspace solid-phase
      microextraction gas chromatography-mass spectrometric (HS-SPME-GC-MS) coupled
      with multivariate analysis. As a result, 95 volatiles have been analyzed from the
      fingerprints, and ultimately six of which were identified as volatile biomarkers
      of the kiwifruit cultivars studied, which are formic acid octyl ester, 2
      Methylbicyclo[4.3.0]non-1(6)-ene, 1-ethoxy-2,4-hexadiene, and 2-methyl-5-(1
      methylethyl)-bicyclo[3.1.0]hex-2-ene for Jintao (A. chinensis), and 1-methoxy-2
      methyl-benzene and (E,E)-2,4-heptadienal for Cuiyu (A. deliciosa), respectively.
      Since the samples of each cultivar were in various maturities, these compounds
      could be taken as the maturity-independent volatile biomarkers for the kiwifruit
      cultivars, which would be valuable for marker-assisted flavour breeding in the
      kiwifruit production.

PMID- 30236670
TI  - Anticholinergic effects of Actinidia arguta fruits and their polyphenol content
      determined by liquid chromatography-photodiode array detector-quadrupole/time of
      flight-mass spectrometry (LC-MS-PDA-Q/TOF).
AB  - This study discusses polyphenolic compounds identified and quantified in
      Actinidia arguta fruits by LC-MS-PDA-Q/TOF method and in vitro anticholinergic
      activity. Notably, of 31 compounds, including 16 flavonols, 7 flavanols, 7
      phenolic acids, and 1 anthocyanin were identified or tentatively identified on
      the basis of their retention times, accurate mass measurements and subsequent
      mass fragmentation data, or by comparison with reference substances and
      literature. Among the detected compounds, 27 were reported for the first time in
      A. arguta fruits. The content of total polyphenols equal 845.54 mg/100 g dry
      weight (dw), and flavanols predominat (92% of total phenolic compounds). Flavonol
      derivatives, mainly glycosylated and acetylated forms of quercetin (22.64 mg/100
      g dw) and kaempferol (18.40 mg/100 g dw) were quantified. The total content of
      phenolic acids was 29.63 mg/100 g dw, and neochlorogenic acid predominant. This
      anticholinergic activity effect of A. arguta fruits can be explained by the
      Pearson's correlation found between flavonols (r = 0.709 and 0.678), phenolic
      acids (r = 0.513 and 0.487), flavan-3-ols (r = 0.466 and 0.443) and anthocyanins
      (r = 0.312 and 0.301) for acetylcholinesterase (AChE) or butylcholinoesterase
      (BuChE), respectively. The data compiled from the quantitative polyphenol
      indicate that A. arguta fruits could be regarded as a promising source of
      bioactive functional food.

PMID- 30236671
TI  - Surfactant TWEEN20 provides stabilisation effect on anthocyanins extracted from
      red grape pomace.
AB  - Red grape pomace, a wine-making by-product is rich in anthocyanins and has many
      applications in food and pharmaceutical industry. However, anthocyanins are
      unstable during processing and storage. This study aimed to investigate the
      stability of anthocyanins obtained by hydroalcoholic extraction (with and without
      sorbic acid) and colloidal gas aphrons (CGA) separation; a surfactant (TWEEN20)
      based separation. Anthocyanins in CGA samples showed higher stability (half-life
      = 55 d) than in the crude extract (half-life = 43 d) and their stability
      increased with the concentration of TWEEN20 in the CGA fraction (6.07-8.58 mM).
      The anthocyanins loss in the CGA sample (with the maximum content of surfactant,
      8.58 mM) was 34.90%, comparable to that in the crude ethanolic extract with
      sorbic acid (EE-SA) (31.53%) and lower than in the crude extract (44%). Colour
      stabilisation was also observed which correlated well with the stability of
      individual anthocyanins in the EE and CGA samples. Malvidin-3-o-glucoside was the
      most stable anthocyanin over time.

PMID- 30236672
TI  - Magnetic solid phase extractions of Co(II) and Hg(II) by using magnetized C.
      micaceus from water and food samples.
AB  - A new bio-MSPE sorbent based on the use of C. micaceus and gamma-Fe2O3 magnetic
      nanoparticle was prepared for the preconcentrations of Co(II) and Hg(II).
      Critical parameters including pH, flow rate, quantity of C. micaceus, quantity of
      gamma-Fe2O3 magnetic nanoparticle, eluent (type, concentration and volume),
      sample volume, and foreign ions were examined. Surface structure and variations
      after interaction with Co(II) and Hg(II) of bio-MSPE sorbent were investigated by
      FT-IR, SEM, and EDX. The impact of bio-MSPE column reusage was also tested. The
      biosorption capacities were determined as 24.7 mg g-1 and 26.2 mg g-1,
      respectively for Co(II) and Hg(II). Certified reference materials were utilized
      to find out the accuracy of the prepared bio-MSPE method. This novel bio-MSPE
      method was accomplished by being applied to real food and water samples. In
      particular, it will be possible to make use of C. micaceus as new alternatives,
      in environmental biotechnology applications.

PMID- 30236673
TI  - Antioxidant and antimicrobial efficacy of a biflavonoid, amentoflavone from
      Nandina domestica in vitro and in minced chicken meat and apple juice food
      models.
AB  - A biflavonoid, amentoflavone isolated from Nandina domestica and characterized by
      NMR spectral-data analyses was assessed for its antioxidant, and antibacterial
      potential in vitro and in food-model systems. Amentoflavone exhibited potent
      antioxidant ability (19.21-75.52%) on scavenging DPPH, ABTS, superoxide, and
      hydroxyl radicals. Fluorescent images confirmed bacterial membrane depolarization
      of both the tested pathogens Staphylococcus aureus and Escherichia coli, with a
      significant reduction in cell viabilities at their respective MIC of 62.5 and 125
      ug/mL. Increasing rates of membrane permeability observed in 260 nm-absorbing
      material, potassium ion, extracellular ATP, and relative electrical conductivity
      assays confirmed antibacterial mechanistic role of amentoflavone as also
      evidenced by microscopic studies of SEM and TEM. There was a marked inhibitory
      effect of amentoflavone with a significant reduction in cell counts of S. aureus
      and E. coli in minced chicken and apple juice at 4  degrees C, thus suggesting
      its nutritional enhancing efficacy as a natural antioxidant and antimicrobial
      agent.

PMID- 30236674
TI  - Characterization of phytochemical mixtures with inflammatory modulation potential
      from coffee leaves processed by green and black tea processing methods.
AB  - Our previous study reported that different tea processing methods along with the
      age of coffee leaves affected antioxidant and anti-inflammatory bioactivities;
      however, identification of phytochemical components or associated mixtures that
      contribute to the anti-/pro-inflammatory activities was not determined. Herein,
      we report results of additional experiments designed to characterize the
      phytochemical composition of fractionated coffee leaf extract, derived from
      Japanese-style-green-tea-process-young (JGTP-Y) and black-tea-process-mature (BTP
      M) leaves and related these data to anti-/pro-inflammatory activities. The
      aqueous fraction of BTP-M coffee leaves induced nitric oxide (NO), iNOS, COX-2,
      IL-6 and IL-10 production in Raw 264.7 cells. A 40% methanol fraction possessed
      greatest anti-inflammatory activities in IFN-gamma and LPS treated Raw 264.7
      cells (P < 0.05). The anti-inflammatory activities of coffee leaf fractions could
      not only be attributed to chlorogenic acids, mangiferin, rutin, and caffeine
      content, but possibly subtle interactions of mixtures of bioactive molecules.

PMID- 30236675
TI  - Effect of a novel Lactobacillus paracasei starter on sourdough bread quality.
AB  - The novel Lactobacillus paracasei K5 strain, recently isolated from Greek cheese,
      was evaluated as potential sourdough bread starter. Breads were made using
      different amounts of L. paracasei sourdoughs as well as traditional sourdough for
      comparison. Quality characteristics of the breads (acidity and rising) were
      examined, as well as rope spoilage through macroscopic observations and molecular
      analysis (PCR-DGGE). The highest acidity levels (3.15 g lactic acid and 1.13 g
      acetic acid per kg of bread) and better resistance to rope spoilage were observed
      when bread contained 30% w/w L. paracasei K5 sourdough. Spoilage in the L.
      paracasei K5 breads was observed at 15-16 days, 5 days later than the control
      breads. In addition, L. paracasei K5 sourdough improved the bread sensory
      properties, as reflected by consumer preference and GC/MS analysis of aroma
      volatiles. Therefore, L. paracasei K5 can be successfully used for sourdough
      bread making with good quality and extended shelf-life.

PMID- 30236676
TI  - Interaction characterization of preheated soy protein isolate with cyanidin-3-O
      glucoside and their effects on the stability of black soybean seed coat
      anthocyanins extracts.
AB  - The interactions of soy protein isolate with cyanidin-3-O-glucoside were
      investigated to study the protective effect of protein on anthocyanin's stability
      by UV-Vis spectrophotometry, Fourier transform infrared spectroscopy, circular
      dichroism and fluorescence spectroscopy. Preheat treatment and binding of
      cyanidin-3-O-glucoside effectively changed the secondary structure of soy protein
      isolate, with a decrease in alpha-helix, random coil structure and an increase in
      beta-sheet and beta-turn. The soy protein isolate preheated at 121  degrees C
      exhibited a strong binding affinity towards cyanidin-3-O-glucoside with strong Ks
      of 147.40 * 104 M-1 and also effectively increased the thermal and oxidation
      stabilities of black soybean seed coat extract via decreasing the degradation
      rate by 67% and 23%, respectively. Soy protein isolate interacted with cyanidin-3
      O-glucoside mainly through hydrophobic interactions and static quenching process.
      Altogether, the results suggested that preheated soy protein isolate-cyanidin-3-O
      glucoside interaction could effectively protect anthocyanins' stability through
      strong binding affinity influenced by the systematic alterations in the secondary
      structure.

PMID- 30236677
TI  - Parameters of the fermentation of soybean flour by Monascus purpureus or
      Aspergillus oryzae on the production of bioactive compounds and antioxidant
      activity.
AB  - The objective of this work was to evaluate the effects the solid-state
      fermentation parameters of defatted soybean flour (DSF) by Monascus purpureus or
      Aspergillus oryzae on the bioactive compounds. Central composite rotatable
      design, multi-response optimization, and Pearson's correlation were used. The
      fermentation parameters as initial pH (X1), DSF-to-water ratio (X2), and
      incubation temperature (X3) were taken as independent variables. The function
      responses were isoflavone content, total phenolic content (TPC), and antioxidant
      activity. All fermentation parameters affected the isoflavone content when
      fermented by Monascus purpureus, whereas the TPC or antioxidant activities
      remained almost unchanged. For the fermentation by Aspergillus oryzae, all the
      function responses were influenced by X2 and X3 and were independent of the X1.
      Estimated optimum conditions were found as x1 = 6.0, x2 = 1:1, and x3 = 30 
      degrees C for both fungi. Achieving suitable fermentation parameters is essential
      to increase bioactive compounds in the DSF that makes it promising for food
      industrial applications.

PMID- 30236678
TI  - Preparation of starch dough using damaged cassava starch induced by mechanical
      activation to develop staple foods: Application in crackers.
AB  - This study focused on evaluating the feasibility of using damaged cassava starch
      (DCS) to exploit staple foods. Cassava starch was subjected to damage induced by
      mechanical activation to obtain DCS with various degrees of damage. The increase
      in damage level of cassava starch led to a slight increase in amylose content and
      reduction in crystallinity. Damage level exerted a major influence on the pasting
      properties and interaction between DCS and water. SEM analysis showed that DCS
      tended to cohere together to form a unique dough structure in the presence of
      water when damage level was not less than 11.51%. Texture properties of the
      starch dough with damage levels of 11.51% and 15.37% were similar with those of
      wheat flour dough. Cracker made of DCS had acceptable sensory qualities
      comparable to the wheat flour counterpart. These findings confirmed that using
      DCS for the development of staple foods by the starch dough was practicable.

PMID- 30236679
TI  - Determination of citrus juice coumarins, furanocoumarins and methoxylated
      flavones using solid phase extraction and HPLC with photodiode array and
      fluorescence detection.
AB  - A synergistic combination of analytical techniques was developed for the
      simultaneous determination of the three most biologically active chemical
      families in citrus juices: methoxylated flavones, coumarins, and furanocoumarins.
      No rapid methodology has been available to determine them together. A solid phase
      extraction concentrated these groups and a ternary reverse phase HPLC gradient
      completely resolved them from other juice components. Two coumarins, isomeranzin
      and osthole, were identified in a sweet orange (C. sinensis) cultivar,
      Changyecheng, for the first time. Pummelo juice was characterized by coumarin and
      furanocoumarin epoxides such as meranzin and epoxybergamottin. No epoxides were
      observed in the more acidic juices. Added furanocoumarin epoxides hydrolyzed
      rapidly in the most acidic juices. The ratios of the UV peak areas at 320 nm to
      the fluorescence emission peaks as well as the ratio of fluorescence emission
      peaks at 450-400 nm could be used to identify chromatographic peaks.

PMID- 30236680
TI  - Effect of liquid-state fermentation on the antioxidant and functional properties
      of raw and roasted buckwheat flours.
AB  - The influence of liquid-state fermentation (LSF) by selected lactic acid bacteria
      (LAB) and Rhizopus oligosporus fungi on the content of rutin and total phenolic
      compounds (TPC), antioxidant capacity measured by ABTS test, FRAP assay and
      photochemiluminescence technique, and the inhibitory activity against formation
      of fluorescent advanced glycation end-products (AGEs) in vitro of raw and roasted
      buckwheat flours was studied. LSF caused a slight, specific LAB-dependent
      increase in TPC and a decrease in rutin content. Fermented raw buckwheat flours
      contained higher amounts of rutin and TPC with one exception when the highest
      increase in TPC was noted in roasted flour fermented by fungi. A LAB-dependent
      difference in the antioxidant capacity of buckwheat flours was noted while the
      inhibitory activity of fermented flours against AGEs formation was generally
      reduced. It can be concluded that LSF with selected LAB and fungi may improve the
      antioxidant and functional properties of buckwheat flours.

PMID- 30236681
TI  - Physicochemical properties and toxicity of cocoa powder-like product from roasted
      seeds of fermented rambutan (Nephelium lappaceum L.) fruit.
AB  - A novel way to fully utilize rambutan fruit and seed is to ferment peeled fruits
      followed by drying and roasting, and use the seeds to produce seed powder similar
      to that of cocoa powder. Hence, the objective of this study was to optimize the
      roasting time and temperature of rambutan fruit post-fermentation and drying, and
      to produce a cocoa-like powder product from the seeds. Parameters monitored
      during roasting were colour and total phenolic content, while seed powder
      obtained using optimized roasting conditions was analyzed for its physicochemical
      properties and toxicity. The latter was examined using the brine shrimp lethality
      assay. Results showed that the roasted seed powder possessed colour and key
      volatile compounds similar to that of cocoa powder. Besides, the brine shrimp
      lethality assay indicated that the roasted seed powder was non-toxic. Thus, the
      fruit, including its seed could be fully utilized and subsequently, wastage could
      be reduced.

PMID- 30236682
TI  - Incorporation of dietary fiber on the cookie dough. Effects on thermal properties
      and water availability.
AB  - In the present work it was analyzed the water mobility by characterizing the
      thermo-gravimetric analysis of the cookie dough with the incorporation of dietary
      fibers. The fibers analyzed were: inulin (IN), oat fiber (OF), high amylose maize
      starch (RSII) and phosphate distarch-phosphate (RSIV). Four tests were performed:
      thermo-gravimetric analysis (TGA), pasting profile analysis using water and a
      solution of 50% sucrose as a solvent, and the study of the ultrastructure of the
      flour and fiber by SEM and particle size distribution. Changes in the thermo
      gravimetric profile were explained by the pasting profile of composites and the
      ultrastructure of the wheat flour and fibers. OF and IN incorporation changed
      substantially dough water loss profile and rate. The addition of fibers produced
      a decrease in the starch pasting profile and inulin showed the highest reduction
      since less water was available for the hydration of wheat flour starch granules.

PMID- 30236683
TI  - Similarities and differences of the volatile profiles of six spices explored by
      Proton Transfer Reaction Mass Spectrometry.
AB  - Aroma properties of spices are related to the volatile organic compounds (VOCs)
      present, which can provide distinct analytical signatures. The aim of the study
      was to examine similarity and diversity of VOC profiles of six common market
      spices (black/white pepper, chili paprika, cinnamon, nutmeg and saffron). The key
      volatiles were identified by PTR-TOFMS. Twelve samples per spice were subjected
      to PTR-Quadrupole MS (PTR-QMS) and Principal Component Analysis to compare the
      groups and examine diversity. With PTR-TOFMS, 101 volatile compounds were
      identified as total sum across all samples by mass and comparing them with
      literature data. Some spices comprised key character aroma compounds, e.g.
      cinnamaldehyde in cinnamon. For others, VOC groups, such as terpenes, acids and
      aldehydes topped the list. The PTR-QMS in combination with variables selection
      resulted in distinct PCA patterns for each spice. Variation within the spice
      groups was observed, but varied with the kind of spice. The results are valuable
      for future authentication studies.

PMID- 30236684
TI  - The influence of the extraction temperature on polyphenolic profiles and
      bioactivity of chamomile (Matricaria chamomilla L.) subcritical water extracts.
AB  - The main goal of this research was to determine the relationship among chemical
      structure, bioactivity and temperature of chamomile during subcritical water
      extraction in isobaric conditions (45 bar) at seven different temperatures (65
      210  degrees C). The influence of temperature on phenolic profiles was defined by
      UHPLC-HESI-MS/MS. The overall results indicate that the presence of conjugated
      double bonds, side chains, glucose moiety or ether moiety in molecules influence
      the efficiency of polyphenols' extraction in subcritical water. In terms of
      antioxidant activity, the extracts were the most active towards ABTS radicals
      (IC50 = 7.3-16.8 ug/mL), whereby temperature of 150  degrees C was optimal. On
      the other hand, the extracts obtained at 115  degrees C showed highest
      cytotoxicity. Inhibition of alpha-amylase and alpha-glucosidase was the highest
      at 65 and 85  degrees C, i.e. 0.51 and 4.13 mmolAE/g, respectively. Activity
      against tyrosinase was the highest at 210  degrees C (17.92 mgKAE/g). The data
      showed that different non-phenolic compounds may also participate in bio
      activities of the extracts.

PMID- 30236685
TI  - Structure identification of alpha-glucans from Dictyophora echinovolvata by
      methylation and 1D/2D NMR spectroscopy.
AB  - Dictyophora echinovolvata is a kind of edible mushroom in the Dictyophora genus,
      of which polysaccharide is an important chemical substance. Herein, three
      polysaccharide fractions (DEP-4P, DEP-6P and DEP-8P) were prepared from water
      extract of D. echinovolvata using gradient ethanol precipitation method. Their
      chemical structures were analyzed by methylation analysis and 1D/2D NMR
      spectroscopy. Molecular weights were determined by multi-angle laser light
      scattering combined with size-exclusion chromatography (HPSEC-MALLS). HPSEC data
      showed that DEP-4P had the highest values of molecular weight, intrinsic
      viscosity and hydrodynamic radius. DEP-6P and DEP-8P had lower molecular weights,
      which contributed to their easily distinguished 1D and 2D NMR spectra.
      Methylation and NMR analysis suggested that the three fractions were linear alpha
      (1 -> 4)-glucans with alpha-Glcp residues linked to the backbone at C-6.
      Differences among the three fractions were the molar ratios of the identified
      glycosidic bonds. Repeating units of polysaccharides from D. echinovolvata were
      proposed as follows.

PMID- 30236686
TI  - Characterizing the phenolic constituents and antioxidant capacity of Georgia
      peaches.
AB  - Acetonic crude phenolic extracts of six Georgia peach cultivars were prepared and
      separated into low- and high-molecular-weight (LMW and HMW) fractions by Sephadex
      LH-20 column chromatography. Further characterization via RP-HPLC-ESI-MS
      identified the main phenolics as hydroxycinnamates, (+)-catechin, and
      proanthocyanidins with degrees of polymerization up to seven. The LMW phenolics
      of the commercial cultivar, 'July Prince', were further chromatographed and
      examined by RP-HPLC-ESI-MS. Derivatives of phenolic acids and flavan-3-ols, along
      with eriodictyol and quercetin diglycosides, were identified. Antioxidant
      capacities of the LMW and HMW fractions were determined using in vitro assays. H
      ORACFL and FRAP assays gave values of 872 to 2428 MUmol Trolox eq./100 g f.w. and
      309 to 432 MUmol Fe2+ eq./100 g f.w., respectively. The total phenolics content
      (TPC) was also measured; correlations between TPCs and antioxidant assays
      indicated that the HMW fractions of peach extracts were major contributors to the
      antioxidant capacity of the cultivars analyzed.

PMID- 30236687
TI  - Improved bactericidal capacity of UV-B radiation against E. coli strains by
      photosensitizing bacteria with fructosazine - An advanced Maillard reaction
      product.
AB  - This study investigated the effect of UV-B irradiation and the combinational
      effect with glucosamine caramel, fructosazine and riboflavin on the antimicrobial
      activities against Bacillus subtilis (ATCC 6633) and two strains of Escherichia
      coli (AW 1.7 and ATCC 25922). The quantum yield of fructosazine was two times
      less than that of tryptophan, indicating its ability to emit fluorescent light
      but less efficiently than tryptophan. UV-B treatment alone was efficient to
      achieve a bactericidal effect for both E. coli stains tested, however no effect
      was found for Bacillus subtilis for up to 80 mJ/cm2 UV-B. The combination of UV-B
      with photosensitizers fructosazine, glucosamine caramel and riboflavin enhanced
      the UV-B efficacy against E. coli strains at lower UV-B doses, while Bacillus
      subtilis ATCC 6633 was more resistant to the treatment combinations. High
      performance liquid chromatography showed the production of different fructosazine
      reaction products occurred during irradiation, including the possible formation
      of endoperoxides.

PMID- 30236688
TI  - An insight into the health benefits of fermented soy products.
AB  - The current review was aimed to summarize the nutritional values and various
      health benefits of fermented soy products. Several previous researches proved
      that soy products rich in protein can reduce the serum concentrations of total
      cholesterol, low-density lipoproteins (LDLs), and triglycerides if consumed
      instead of animal protein. Apart from these lipid-lowering effects, fermented soy
      products also proved to be effective in attenuating the effects of diabetes
      mellitus, blood pressure, cardiac disorders and cancer-related issues. The
      nutritional value of the fermented soy products gains much attention due to its
      increased levels compared to the non-fermented ones. The origin, compositions,
      nutritional values of different fermented soy products and health-promoting
      benefits of fermented soy products were systematically reviewed. Hence the in
      depth analysis of the various research findings on fermented soy products,
      beneficial activities may help the future researchers to derive a conclusion on
      its beneficial effects on health.

PMID- 30236690
TI  - In depth study of phenolic profile and PTP-1B inhibitory power of cold-pressed
      grape seed oils of different varieties.
AB  - This paper investigates the phenolic composition of 17 monocultivar commercial
      cold-pressed grape seed oils. Chromatographic profiles showed the presence of
      more than 28 molecules, 11 of which were successfully identified by HPLC-DAD-MS
      TOF and HPLC-FLD analysis. Pinoresinol, ethyl caffeate and ethyl gallate were
      detected for the first time in these oils. The total phenolic content ranged
      between 0.83 mg/kg for Viognier sample to 15.16 mg/kg for Merlot org sample. The
      detected ethyl esters can be suggested as markers to evaluate the intensity of
      fermentation in grape seeds before oil extraction, and to control the sensorial
      quality of the produced oils. In addition, the inhibitory power of these phenolic
      extracts against Protein Tyrosine Phosphatase 1B enzyme (PTP-1B), overexpressed
      in type-two diabetes, was investigated for the first time. Data highlighted a
      good correlation between total phenolic content and inhibitory power, with
      pinoresinol, p-coumaric acid and quercetin making the greater contributions.

PMID- 30236689
TI  - Lipase-catalyzed glycerolysis of anchovy oil in a solvent-free system:
      Simultaneous optimization of monoacylglycerol synthesis and end-product oxidative
      stability.
AB  - The production of mono- and diacylglycerols rich in polyunsaturated fatty acids
      is achieved in this study, by solvent-free glycerolysis of anchovy oil with
      lipase PS-DI from Burkholderia cepacia. Attention is focused on the oxidative
      stability of the reaction products, determined in terms of induction time (It).
      The effects of glycerol/triacylglycerol molar ratio, enzyme concentration, and
      reaction temperature on mono- and diacylglycerol production and It are all
      assessed. The operating conditions that optimized monoacylglycerol yields and
      oxidative stability were a glycerol/triacylglycerol ratio of 3/1, 9.0% (w/w)
      Lipase PS-DI, a stirring rate of 200 rpm, and a reaction time of 4 h, at 45.8 
      degrees C, producing a content of 24.8% and 51.9% of mono- and diacylglycerols,
      respectively, over an It of 1.41 h. The glycerolysis conditions determined by
      simultaneous optimization strategy increased the oxidative stability of the
      glycerolysis products by 68%, which rose from 0.84 h (individual optimization) to
      1.41 h.

PMID- 30236691
TI  - Washing rice before cooking has no large effect on the texture of cooked rice.
AB  - Washing rice before cooking is common to remove dust and any remaining bran
      produced by the milling process. In this study, the effect of washing procedure
      on the textural properties of cooked rice, and its relations to starch leaching
      and the molecular structure of leached starch are investigated. Statistical
      analysis indicated that the washing procedure does not significantly affect
      either hardness or stickiness of cooked rice, but the interaction between rice
      variety and washing times on stickiness is significant. The components of leached
      materials, chain-length distribution (CLD), and molecular size of leached starch
      are significantly different from those of the surface materials, but not largely
      varied between rices with different washing times, which helps explain the
      molecular mechanism of the causes of these textural results. This indicates for
      the first time that, the adhering materials on the surface of raw rice grains do
      not contribute to the texture of cooked rice.

PMID- 30236692
TI  - A simple and sensitive SERS quantitative analysis method for urea using the
      dimethylglyoxime product as molecular probes in nanosilver sol substrate.
AB  - Under the light wave irradiation, the stable and highly surface enhanced Raman
      scattering (SERS) active silver nanosol (AgNP) was prepared by reduction of
      AgNO3, using sodium citrate as reducer. Urea reacted with dimethylglyoxime to
      produce 4,5-dimethyl-2-imidazole ketone that exhibited a strong SERS peak at 1320
      cm-1 in the as-prepared AgNPs substrate. Under the selected conditions, the
      increased SERS intensity DeltaI was linear to urea concentration in the range of
      8.25-825 nM, with a detection limit of 4.92 nM. Accordingly, a new, simple SERS
      quantitative analysis method for trace urea in foods was established, with
      relative standard deviation of 0.92-4.8% and recovery of 97.4-101%.

PMID- 30236694
TI  - Wheat (Triticum aestivum L.) flour free lipid fractions negatively impact the
      quality of sponge cake.
AB  - The functionality of wheat flour lipids in sponge cakes prepared from flour,
      sugar, eggs and leavening agents only was investigated by altering their location
      or content in flour. Hexane (hex) or the more polar hexane:isopropanol (3:2 v/v)
      (hex:isoprop) were used to impact free flour lipid (FFL) or both FFL and bound
      flour lipid (BFL) fractions, respectively. Flour from which the FFLs were removed
      resulted in significantly improved cake volumes and crumb structures. Additional
      removal of part of the BFLs did not further impact cake quality. Prior contact of
      flour with hex:isoprop followed by gently removing the solvent broke native
      interactions between BFLs and starch or gluten and relocated more lipids than did
      hex. Cakes from flour with relocated lipids had coarse crumb structures. Our
      study demonstrates that FFLs and relocated flour lipids negatively impact sponge
      cake quality by disturbing air-liquid interface stabilization during mixing and
      the early phases of baking.

PMID- 30236693
TI  - Effects of in vitro gastrointestinal digestion and colonic fermentation on a
      rosemary (Rosmarinus officinalis L) extract rich in rosmarinic acid.
AB  - The potential phytochemical losses occurring throughout the sequential steps of
      in-vitro gastrointestinal digestion and colonic fermentation of a rosemary
      aqueous extract were investigated. Crude (CE), digested (DE) and fermented (FE)
      extracts were characterized in terms of their phenolic profile and biological
      activities. Rosmarinic acid was the phytochemical that underwent the most
      significate transformation during digestion and fermentation, which amounted to
      60% compared to the 26% degradation of the total phenolics. Overall, the
      simulated digestion step decreased the antioxidant activity estimated by DPPH,
      ABTS, FRAP, ORAC and TBARS assays. Both CE and DE did not present
      antiproliferative potential, however, FE exhibited a pronounced cytotoxic
      activity (GI50 = 116 ug/mL) against HeLa cells. CE and DE showed to be moderate
      inhibitors of methicillin-resistant Staphylococcus aureus (MRSA), methicillin
      susceptible S. aureus (MSSA), S. aureus, Listeria monocytogenes, whilst the FE
      acted as a moderate inhibitor of MRSA and MSSA.

PMID- 30236695
TI  - Untargeted DNA-based methods for the authentication of wheat species and related
      cereals in food products.
AB  - New food commodities, particularly pasta, bread and cookies, made with mixed
      flours containing ancient wheat species and other cereals, have become popular in
      recent years. This calls for analytical methods able to determine authenticity of
      these products. Most DNA-based methods for the authentication of foodstuff rely
      on qPCR assays specifically targeting each plant species, not allowing the
      identification of unsearched ingredients. Moreover, the discrimination among
      closely related plant species, particularly congeneric ones like Triticum spp,
      remains a challenging task. DNA fingerprinting through tubulin-based polymorphism
      (TBP) and a new assay, TBP light, have been optimized for the authentication of
      different wheat and farro species and other cereals and tested on a set of
      commercial food products. The assay has a sensitivity of 0.5-1% w/w in binary
      mixtures of durum wheat in einkorn or emmer flour and was able to authenticate
      the composition of test food sample and to detect possible adulterations.

PMID- 30236696
TI  - Multi-element rice grains analysis by ICP OES and classification by processing
      types.
AB  - As major food staple, rice (Oryza sativa L.) is cultivated in irrigated fields
      absorbing widely trace elements wich may or may not migrate during processing
      types. Thus, we aimed to evaluate five national rice brands found in local
      market, in order to verify concentration of elements As, Ba, Ca, Cd, Co, Cr, Cu,
      Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Sb, Se, Sn, Sr, V, Tl and Zn, presenting the
      differences and migration patterns between brown, parboiled and polished rice for
      each brand. Data were evaluated using ANOVA, post-hoc Tukey and PCA. The two
      major components presented 94.33% variance, indicating strong differentiation in
      samples by their processing types from their mineral composition. K is widely
      distributed over the grain, Mg, Fe and Ba are more distributed in the outer
      layers being more susceptible to loss, and Ca, Sr and Zn are more sensitive to
      the parboiling hydrothermal process.

PMID- 30236697
TI  - Comparison of (poly)phenolic compounds and antioxidant properties of pomace
      extracts from kiwi and grape juice.
AB  - The aim of this study was to evaluate the phenolic profile of grape and kiwi
      juice pomace by HPLC-ESI-MS, and their correlation with antioxidant properties
      determined with DPPH, FRAP and OH scavenging assays. A total of 32 compounds have
      been identified including anthocyanins, flavonols, flavan-3-ols and phenolic
      acids. Significantly higher relative amounts of anthocyanin monoglucosides,
      flavan-3-ols (catechin, epicatechin, and procyanidin), and flavonols (quercetin
      and its derivatives) were found for grape pomace. Whereas kiwi pomace contained
      higher amounts of quinic acid, caffeic acid and its derivatives. Although grape
      pomace had higher total phenolic content (TPC), it showed lower OH scavenging
      capacity than kiwi pomace, but better DPPH scavenging activity and reducing
      power. This indicated that the antioxidant activities do not only rely on the TPC
      but also associate with their phenolic profiles. Overall the two pomaces could
      potentially be exploited as an inexpensive source of natural antioxidants for
      food production.

PMID- 30236698
TI  - Synthesis of omega-3 ethyl esters from chia oil catalyzed by polyethylene glycol
      modified lipases with improved stability.
AB  - Enzymatic synthesis of fatty acid ethyl esters (FAEE) from chia (Salvia hispanica
      L.) oil has been performed with different modified derivatives and compared with
      commercial immobilized lipases to produce omega-3 rich FAEE. Therefore, the main
      objective was to synthesize omega-3 esters from chia oil catalysed by
      polyethylene glycol-modified lipases using a biocatalyst with higher stability
      than commercial derivatives. Lipase from Thermomyces lanuginosus (TLL) was
      immobilized by hydrophobic adsorption on Sepabeads C-18 followed by a
      physicochemical coating of lipase surface with a dense layer of PEG. Ethanolysis
      reactions were carried out using pressurized liquid extracted chia seed oil and
      with different lipase derivatives to compare the omega-3 FAEE yield and ratio of
      reaction products, which were analysed by HPLC-ELSD. Furthermore, reutilization
      of lipase derivatives was studied to evaluate the stability after several
      reaction cycles to minimize decreasing of catalytic activity and develop a
      feasible enzymatic process for food industrial applications.

PMID- 30236699
TI  - A competitive immunoassay for biotin detection using magnetic beads and gold
      nanoparticle probes.
AB  - Haptens are small molecules with low molecular weight that include biotin and
      many toxins in food. In this study, we used biotin as a model molecule for hapten
      detection. In this competitive immunoassay anti-biotin antibody-modified magnetic
      beads (Ab-MBs) and biotinylated thiol-DNA gold nanoparticles (biotin-GNPs) were
      used. The assay contains three reactions, the mixing of the sample and Ab-MBs,
      the capture of biotin-GNPs by Ab-MBs and the magnetic attraction. When biotin
      molecules were absent, the solution was transparent because biotin-GNPs bound to
      Ab-MBs which were caught by an external magnetic field. When biotin was present,
      the supernatant was red because the Ab-MBs bound to the analytes and the gold
      nanoparticles were still in solution. It was possible to complete all the
      operating steps in 15 min. The limit of detection (LOD) was 2 pmol. This rapid
      competitive-immunoassay has potential for application in detection of other
      haptens.

PMID- 30236700
TI  - Lipase-catalyzed solvent-free synthesis of erythorbyl laurate in a gas-solid
      liquid multiphase system.
AB  - Erythorbyl laurate is a potential food additive as a multi-functional emulsifier
      having antioxidant and antimicrobial activities. In this study, a gas-solid
      liquid multiphase system (GSL-MPS) was established to enhance the production
      yield of erythorbyl laurate in a lipase-catalyzed solvent-free synthesis. The
      significant reaction variables were optimized as follows: substrate molar ratio
      of 2:1 (lauric acid:erythorbic acid) and enzyme concentration of 120 mg/mL (840
      PLU/mL). Under these conditions, the maximum production yield in GSL-MPS was
      13.974 mg/mL, which is 8.60- and 4.26-fold higher than the yields obtained in an
      organic solvent monophase system (OS-MPS) and a solid-liquid biphase system (SL
      BPS), respectively. Moreover, the operational stability of the immobilized lipase
      was significantly improved in GSL-MPS compared with OS-MPS. These results
      indicate that GSL-MPS can be an enzymatic reaction system facilitating efficient
      production of ester compounds as a means of increasing production yields and the
      reusability of the immobilized lipase.

PMID- 30236701
TI  - Biomarkers-based classification between green teas and decaffeinated green teas
      using gas chromatography mass spectrometer coupled with in-tube extraction
      (ITEX).
AB  - For identifying discriminatory biomarkers between green tea (GT) and
      decaffeinated green tea (dGT), in-tube extraction (ITEX)-gas chromatograph-mass
      spectrometer (GC-MS) was optimized to determine volatile organic compounds (VOCs)
      from tea products. Biomarker selection between GT and dGT was then conducted by
      random forest (RF). Optimized ITEX parameters by central composite design were an
      incubation temperature of 92  degrees C, incubation time of 12 mins, and 36 for
      syringe strokes. A training group of 24 samples and testing group of 21 samples
      were used to RF classification of biomarkers identification. Results revealed
      that 2-hexenal, 2-ethyl furan, indole, and beta-ocimene were selected as
      discriminatory biomarkers between GT and dGT in the training group. Using these
      biomarkers with RF classification algorithms, prediction accuracy for dGT and GT
      were 88.9% and 100%, respectively, which was higher than for other classification
      algorithms. This implies that ITEX-GC-MS can be a promising tool for quality
      control of commercial tea products.

PMID- 30236702
TI  - Effect of single and dual-modifications on stability and structural
      characteristics of foxtail millet starch.
AB  - Foxtail millet starch was modified by annealing (AS), ultra-sonication (US) and a
      combination of the two treatments (annealing and ultra-sonication (AUS) or ultra
      sonication and annealing (UAS)) and they were characterized. Compared to the
      native starch (NS), modified starches particularly UAS contained the highest
      amylose (27.96%). Ultra-sonication prior to annealing had a predominant effect on
      resistant starch (RS) level (UAS-45.59%). Among the modified starches, UAS had
      exhibited superior resistance to acidic (0.94) and shear (0.68) stability.
      Sonication, when used as the second treatment (AUS) elevated the final viscosity
      compared to its counter ones possibly due to the effects of cavitation promoted
      by sonication treatment. UAS had showed an A-type diffraction pattern and
      dominant peaks in FT-IR spectra. It can be inferred that dual modification of
      starch by ultra-sonication followed by annealing had exhibited the most desirable
      properties such as high acid and shear resistance, high freeze-thaw stability and
      improved gel texture.

PMID- 30236703
TI  - Differences in 1-methylcyclopropene sorption dynamics in fresh-cut apple, avocado
      and tomato fruits.
AB  - Fresh-cut (FC) apple, avocado and tomato fruits were examined to determine if
      sorption dynamics previously reported for FC apple were of general occurrence for
      other fruits. Fresh-cut apple consumed headspace 1-MCP at high rates, fully
      depleting 1-MCP in 1.5 h. FC apple pretreated with ascorbate showed 80% reduction
      in sorption rate. Fresh-cut avocado showed moderate sorption, depleting 95% of
      system 1-MCP over 6 h. FC avocado was unaffected by ascorbate. FC tomato showed
      negligible sorption of 1-MCP. Sorption by FC apple and avocado was differentially
      affected by heat. High-temperature pretreatment of FC apple and avocado resulted
      in 80% and 20% reductions in 1-MCP sorption rates, respectively. The data
      indicate that 1-MCP sorption differs significantly between FC tissues of
      different fruits, likely reflecting differences in thermo-tolerant, physical
      sorption processes versus oxidative metabolism. Possible drawbacks in the use of
      1-MCP as a post-processing treatment for FC fruits are discussed.

PMID- 30236704
TI  - UV-C light irradiation enhances toxic effects of chlorpyrifos and its
      formulations.
AB  - UV-C irradiation is widely used in the food industry. However, the health effects
      from dietary exposure to the irradiated pesticide residues retained in foodstuffs
      are underestimated. In this study, technical chlorpyrifos (TCPF) and its oil in
      water (EW) and emulsifiable concentrate (EC) formulations were irradiated by UV
      C, and their photodegradation products were subjected to toxicity assessment,
      including determination of acetylcholinesterase (AChE) activity, genotoxicity and
      oxidative stress using human blood cells as a model system. Toxicity studies were
      performed using the chlorpyrifos concentrations in the range of those proposed as
      the maximum residue levels in plant commodities. TCPF, EW and EC photodegradation
      products induced DNA damage and oxidative stress, and their genotoxicity did not
      decrease as a function of irradiation time. Irradiated TCPF and EC are more
      potent AChE inhibitors than irradiated EW. Accordingly, the application of UV-C
      irradiation must be considered when processing the plants previously treated with
      chlorpyrifos formulations.

PMID- 30236705
TI  - Improved controlled flavor formation during heat-treatment with a stable Maillard
      reaction intermediate derived from xylose-phenylalanine.
AB  - The Maillard reaction intermediate (MRI) and Maillard reaction products (MRPs)
      derived from xylose (Xyl) and phenylalanine (Phe) were prepared, then stored at
      25  degrees C for 60 days. After storage, the contents of flavor compounds and
      the clarity of MRPs solution decreased, and the apparent Z-average hydrodynamic
      diameter (Dh) of particles in the solution increased from 149 to 439 nm. However,
      the MRI solution remained transparent during storage. The concentration of MRI
      only decreased by 6.49%, and A294 of the solution increased slightly yet A420
      remained stable. Numerous flavor compounds in MRPs decreased during heat
      treatment, meanwhile the cross-linking and aggregation of MRPs were intensified,
      and the particles' Dh increased to micron level. The heated MRI solution showed a
      similar appealing profile and flavor fingerprints as the MRPs solution before
      heat treatment. Controlled formation of flavors from MRIs is proposed to be used
      as potential alternative to the existing Maillard flavorings.

PMID- 30236706
TI  - Cooking parameters affect the sodium content of prepared pasta.
AB  - The quantitative effect of different preparation variables on the sodium content
      of cooked dry pasta was evaluated. Semolina spaghetti (<5 mg sodium/100 g) was
      cooked by a typical method (454 g, 5.68 L water, 36 g salt, al dente, no rinsing)
      and after systematic variation of amount of salt, water:pasta ratio, cooking
      volume and time, rinsing, pasta shape, whole grain. Sodium was assayed by ICP-MS,
      including rigorous quality control. Pasta cooked without salt had <5 mg
      sodium/140 g serving, and 247-490 mg/serving when cooked in salted water by the
      different variations. Rinsing reduced sodium by 34%. There was a linear
      relationship between salt concentration in cooking water and sodium in cooked
      pasta; doubling the concentration increased sodium by 243 mg/serving (>10% of
      2300 mg/day), relative to the reference method. No other variables affected
      sodium. Results allow more accurate estimation of sodium intake from cooked
      pasta, since food composition tables that do not reflect variations in cooking
      parameters.

PMID- 30236707
TI  - Olive oil quality classification and measurement of its organoleptic attributes
      by untargeted GC-MS and multivariate statistical-based approach.
AB  - The capabilities of dynamic headspace entrainment followed by thermal desorption
      in combination with gas chromatography (GC) coupled to single quadrupole mass
      spectrometry (MS) have been tested for the determination of volatile components
      of olive oil. This technique has shown a great potential for olive oil quality
      classification by using an untargeted approach. The data processing strategy
      consisted of three different steps: component detection from GC-MS data using
      novel data treatment software PARADISe, a multivariate analysis using EZ-Info,
      and the creation of the statistical models. The great number of compounds
      determined enabled not only the development of a quality classification method as
      a complementary tool to the official established method "PANEL TEST" but also a
      correlation between these compounds and different types of defect. Classification
      method was finally validated using blind samples. An accuracy of 85% in oil
      classification was obtained, with 100% of extra virgin samples correctly
      classified.

PMID- 30236708
TI  - Molar absorptivities (epsilon) and spectral and colorimetric characteristics of
      purple sweet potato anthocyanins.
AB  - Purple sweet potato, a source of acylated cyanidin and peonidin derivatives, is
      commercially available as a food colorant. Our objectives were to determine molar
      absorptivities (epsilon), spectral and colorimetric properties of purple sweet
      potato anthocyanins. Anthocyanins were isolated by semi-preparative HPLC,
      weighed, dried, and redissolved in acidic methanol or water. Anthocyanins were
      diluted in pH 1-9; epsilon, spectra, and color were measured on the methanolic
      and aqueous solutions. Higher epsilon were obtained in 0.1% HCl methanol (10,797
      31,257 L/(mol * cm)) than in aqueous solution pH 1 (8861-24,303 L/(mol * cm)).
      Peonidin-3-sophoroside-5-glucoside had greatest epsilon in pH 1, but in alkaline
      pH, epsilon of acylated Peonidin-3-sophoroside-5-glucoside derivatives were
      greatest. Generally monoacylation decreased epsilon while diacylation increased
      epsilon. Location of acylation also affected epsilon of two Peonidin isomers (pH
      1: 15,999 and 21,011 L/(mol * cm)). All anthocyanins expressed red-pink hues (330
      degrees -13.2 degrees ) in acidic pH and blues (230 degrees -262 degrees ) in
      alkaline pH.

PMID- 30236709
TI  - Rapidly detecting major peanut allergen-Ara h2 in edible oils using a new
      immunomagnetic nanoparticle-based lateral flow assay.
AB  - Ara h2 is a major peanut allergen that induces rashes, vomiting, diarrhea, and
      anaphylactic shock. Since peanut is a major source in producing edible oils
      globally, Ara h2 residues can be present in various edible oils. In this work, an
      immunomagnetic nanoparticle-based lateral flow assay for identifying Ara h2 in
      edible oils is developed. This assay exhibits high sensitivity with a visual
      detection limit of 0.1 mg/kg Ara h2 in oil, and favorable specificity in
      differentiating peanut from seeds and nuts. The calculated CV values of intra-
      and inter-assay were 6.73-10.21% and 4.75-8.57%, respectively, indicating high
      reproducibility. In an analysis of 26 oil products, Ara h2 was detected in two
      peanut oils as 0.122 +/- 0.026 mg/kg and 0.247 +/- 0.027 mg/kg. The entire method
      takes 5 h, including a 3.5-h sample preparation. Hence, this method has the
      potential to be an effective way to screen edible oils for Ara h2.

PMID- 30236710
TI  - ABA-dependent salt and drought stress improve strawberry fruit quality.
AB  - Strawberry crop is very sensitive to osmotic stress conditions. We investigated
      the effect of the stress induced by mild drought (DS) and salt (SS) stresses, on
      molecular, physiological, and metabolic processes in the strawberry crop
      (Fragaria ananassa), cv. Camarosa. The results showed that the fruit yield was
      not affected. Mild DS and SS also resulted in an increased content of phenolics,
      anthocyanins, and l-ascorbic acid, and an increased antioxidant activity. These
      effects were accompanied by increased levels of ABA and its derivatives (phaseic
      and dehydrophasic acids), alongside the upregulation of several genes involved on
      their synthesis. Therefore, the results obtained in this study suggest that mild
      DS and SS improve the functional quality of strawberry fruits through and ABA
      dependent mechanism.

PMID- 30236711
TI  - Cross-linking and film-forming properties of transglutaminase-modified collagen
      fibers tailored by denaturation temperature.
AB  - Transglutaminase (TGase) catalyzing crosslinking between intra- and inter-chain
      glutamine and lysine peptide residues has been used for modifying protein's
      structure. However, its enzymatic performance on albuminoids such as collagen was
      still not completely illustrated. Herein, we investigated the crosslinking
      efficiency of films preheated at different temperatures and estimated its
      physicochemical properties. The electrophoresis results showed that the extracted
      collagen had typical triple helix structure but reduced and even disappeared as
      temperature increased. Accordingly, X-ray diffraction (XRD) indicated that the
      amount of triple helices decreased, corresponding to the decreases in thermal
      stability and mechanical properties of films. TGase crosslinking decreased the
      thickness of all films, while mechanical properties and thermal stability had a
      significant improvement especially at 45  degrees C and 65  degrees C. With the
      proper equilibrium of denature temperature and TGase crosslinking, the tailored
      film-forming properties of collagen can offer a potential to engineer collagenic
      material for biodegradable and edible packaging applications.

PMID- 30236712
TI  - Monitoring anthocyanin degradation in Hibiscus sabdariffa extracts with multi
      curve resolution on spectral measurement during storage.
AB  - This study aims to monitor composition changes in an anthocyanin-rich beverage
      during storage by the means of UV-VIS measurements associated with a multi-curve
      resolution procedure. Hibiscus sabdariffa extract was stored at 37  degrees C for
      50 days and UV-VIS spectra were measured on the extract and the fractions of the
      extract every 5 days. MCR was carried out in two steps, first with the fraction
      and then the extract spectra. The results enabled the main polyphenols initially
      present to be identified, anthocyanins and chlorogenic acid, but also found the
      nature of the main degradation products: the polymers from anthocyanin
      condensation and scission products. In addition, comparison with HPLC analysis
      results showed that the MCR procedure recovered the correct shapes of the
      concentration profiles particularly of anthocyanin and polymer kinetics during
      storage. This work gives perspective for the use of a rapid and efficient
      technique to monitor pigment-rich beverage processing or storage.

PMID- 30236713
TI  - An electrochemical biosensor based on hemoglobin-oligonucleotides-modified
      electrode for detection of acrylamide in potato fries.
AB  - Acrylamide a neurotoxin and strong carcinogen, is found in various thermally
      processed foods. In this study, an electrochemical sensor for detection of
      acrylamide using double stranded DNA (dsDNA)/Hemoglobin (Hb)-modified screen
      printed gold electrode (SPGE) was designed. The immobilization of ssDNA1-SH on
      the surface of SPGE was confirmed by cyclic voltammetry, and the interaction
      between ssDNA2-NH2 and Hb with the ratio 1:1 was characterized by agarose gel.
      The excellent response of the designed biosensor towards acrylamide due to
      acrylamide and Hb adducts and change of reduction/oxidation process of Hb
      Fe(III)/Hb-Fe(II) was determined by square wave voltammetry (SWV). The biosensor
      showed the optimum response at pH 8.0. The linear working range for acrylamide
      was from 2.0 * 10-6 to 5.0 * 10-2 M with a detection limit of 1.58 * 10-7 M. The
      biosensor was suitable for direct determination of acrylamide in water extracted
      of potato fries and displayed good reproductivity and high stability.

PMID- 30236714
TI  - Effect of Spanish-style processing steps and inoculation with Lactobacillus
      pentosus starter culture on the volatile composition of cv. Manzanilla green
      olives.
AB  - The effects of the main steps of Spanish-style processing (alkaline treatment and
      fermentation) on the volatile composition of cv. Manzanilla green olives were
      studied. Both spontaneous and controlled fermentations were considered. In the
      latter case, a Lactobacillus pentosus strain from green olive fermentation brine
      was used as starter culture. The volatile profile was determined by headspace
      solid-phase microextraction (HS-SPME) combined with gas chromatography-mass
      spectrometry (GC-MS). Most of the volatile compounds detected in fresh olives
      decreased or were undetected after alkaline treatment, while several compounds
      (mostly acetic acid, 2-methylbutanoic acid, and ethanol) were formed as a result
      of this treatment. Over 50 new volatile components, mostly esters and phenols,
      appeared as a result of fermentation. The most outstanding finding was a
      considerable increase in 4-ethyl phenol (almost 100-fold increase) in inoculated
      olives compared to the uninoculated product. However, a sensory panel did not
      find significant differences in odor perception.

PMID- 30236715
TI  - Changes in protein properties and tissue histology of tuna meat as affected by
      salting and subsequent freezing.
AB  - The effects of salting and subsequent freezing on the physicochemical and
      histological properties of frozen-thawed tuna meat were investigated. Salting
      facilitated the microstructural recovery as indicated by the decrease or
      disappearance of intracellular holes. The yield of the 0.5 M and 1 M salted
      samples increased by 20% which was evaluated by the mass ratio of products to raw
      material. Morphological transformation from ice columns to spherical or
      ellipsoidal ice crystals was tentatively attributed to the
      extraction/solubilization of myofibrillar proteins, contributing to increased
      water-holding capacity. However, increased thawing loss and centrifuging loss
      after thawing were observed in the 2 M and 3 M salted samples with large ice
      crystals and enlarged extracellular spaces. These modifications were closely
      associated with the changes in protein properties. In conclusion, enhanced water
      holding capacity, high yield, and good freezing stability can be achieved by
      optimal salting.

PMID- 30236716
TI  - Qualitative assessment of 'highly digestible' protein mutation in hard endosperm
      sorghum and its functional properties.
AB  - Sorghum mutants with altered protein body structure have improved protein
      nutritional quality; however, practical methods to accurately track heritability
      of the trait are lacking. We evaluated suitability of the in vitro pepsin assay,
      and a new high-resolution field emission electron microscopy (FE-SEM) method to
      detect the mutation (HD) in hard-endosperm sorghum; and compared the
      physicochemical properties of experimental HD sorghums to wild type (LD) lines.
      FE-SEM reliably resolved sorghum protein body structure, allowing for qualitative
      classification of sorghum as HD or LD. The pepsin assay was less reliable, with
      significant variations across environments. Nevertheless, HD lines averaged
      higher protein digestibility (69.4% raw, 57.6% cooked) than LD lines (61.7% raw,
      45.6% cooked). The HD lines also had better water solubility and starch pasting
      profiles than LD lines. FE-SEM, but not pepsin assay, reliably detects HD
      nutation in sorghum. The HD trait may improve food-use functionality of sorghum.

PMID- 30236717
TI  - Fining with purified grape pomace. Effect of dose, contact time and varietal
      origin on the final wine phenolic composition.
AB  - Fining, which involves the addition of adsorptive material in order to reduce or
      eliminate certain unwanted components, is a common winemaking practice. Fining
      agents affect the wine phenolic compounds, some of which may be reduced. When
      this reduction is experimented by the tannins, a positive effect may result by
      decreasing astringency in the wine, although a decrease in the wine color may
      also take place when the anthocyanins are involved, affecting its quality.
      Recently, grape cell wall material has been tested as a potential fining agent in
      wines, since it shows a high affinity for tannins so that its use could reduce
      wine astringency. In this work, the use of purified grape pomace as fining agent
      is proposed and the effect of different doses and contact times on wine chromatic
      characteristics was investigated as well as how differences in the composition of
      the purified pomace could alter the phenolic composition of a red wine. The
      results showed that a Monastrell purified grape pomace dose of 6 mg/ml and a
      contact time of 5 days could be suitable for decreasing the wine tannin content
      without producing great changes in the wine chromatic characteristics. When
      comparing the effect of purified pomaces from four grape varieties, some
      differences in their capacity to interact with the wine tannins and anthocyanins
      were found, however, the results confirm that the purified grape pomace, a
      byproduct of the enology industry could be a new interesting fining material.

PMID- 30236718
TI  - Quantitative comparison of adsorption and desorption of commonly used sweeteners
      in the oral cavity.
AB  - Adsorption-desorption properties of different sweeteners in the oral cavity were
      evaluated using high performance liquid chromatography-based methodology. Three
      low calorie artificial sweeteners (aspartame, acesulfame potassium and
      sucralose), one steviol glycoside (rebaudioside A), and high fructose corn syrup
      (HFCS) were examined and compared with sucrose at pH 3 and 7 in a model beverage
      matrix. Results indicated that HFCS had the highest adsorption in the oral
      cavity, followed by rebaudioside A and the artificial sweeteners. The
      physicochemical interaction between sweeteners and salivary proteins did not
      affect the adsorption properties significantly as validated from a series of
      characterization techniques.

PMID- 30236719
TI  - Rapid and visual detection of aflatoxin B1 in foodstuffs using aptamer/G
      quadruplex DNAzyme probe with low background noise.
AB  - Contamination of foods by aflatoxin B1 (AFB1) is a common serious problem. To
      improve the efficiency of AFB1 detection, this study aims to develop a sensitive
      aptasensor for detection of AFB1 in food samples based on the catalytic effect of
      aptamer/G-quadruplex DNAzyme probe. The resulting reassembly of this probe in the
      presence of hemin and K+ catalyzes the generation of fluorescent 2,3
      diaminophenazine (DAP) from o-phenylenediamine (OPD). Interestingly, we first
      found that the high background induced by the superfluous hemin can be
      effectively suppressed with the aid of sequential adsorption and magnetic
      separation by magnetic oxidized multiwall carbon nanotubes (Fe3O4@oMWCNTs). This
      aptasensor exhibits a high sensitivity toward AFB1 with a detection limit of 0.02
      ng/mL. The assay also shows higher selectivity for AFB1 compared to other
      reported agents and can be employed to detect AFB1 in foodstuffs, which might
      find broad practical applications in other food contaminants determination.

PMID- 30236720
TI  - Effect of different drying methods on the product quality and bioactive
      polysaccharides of bitter gourd (Momordica charantia L.) slices.
AB  - In this study, three drying methods, namely, hot-air drying, freeze drying (FD),
      and infrared radiation drying (ID), were applied to dry bitter gourd (Momordica
      charantia L.) slices. Results showed that the drying methods had significant
      influences on appearance, color, rehydration ratio, and microstructure of dried
      bitter gourd. FD provided high-quality dried bitter gourd products due to the
      uniform honeycomb network and less collapsed structure. Three water-soluble
      bitter gourd polysaccharides (BPS-H, BPS-F, and BPS-I) were obtained from the
      bitter gourd dried using the three drying methods. The three polysaccharides
      exhibited similar preliminary structural characteristics with different
      monosaccharide compositions and molecular weights. BPS-I obtained from ID-dried
      bitter gourd had higher sugar and uronic acid contents than BPS-H and BPS-F. BPS
      I exhibited stronger antioxidant activities and bile acid-binding capacity in
      vitro than BPS-H and BPS-F. Moreover, BPS-F and BPS-I showed significant alpha
      amylase inhibitory activities in vitro.

PMID- 30236721
TI  - Crystal structure determination of Scylla paramamosain arginine kinase, an
      allergen that may cause cross-reactivity among invertebrates.
AB  - Shellfish are one of the most common causes of food allergy. Arginine kinase (AK)
      is known as an important allergen in shellfish. In the present study, AK from
      crab (Scylla paramamosain) was purified and its crystal structure was determined.
      A comparison of AK from S. paramamosain to AKs of other species showed high amino
      acid sequence and secondary structure identity, while the superposition of
      crystal structures of AKs from different species revealed only slight
      differences. Similarity of the linear epitope regions among species was observed
      in the epitope alignment of AKs; conformational epitopes were located in the
      regions where secondary structure was conserved. The structure of S. paramamosain
      AK is an accurate template for the analysis of the IgE binding pattern, and the
      structure conservation and epitope similarity of AKs among species could help to
      inform our understanding of the cross-reactivity and contribute to the prediction
      of cross-reactivity related epitopes.

PMID- 30236722
TI  - Proteinase and glycoside hydrolase production is enhanced in solid-state
      fermentation by manipulating the carbon and nitrogen fluxes in Aspergillus
      oryzae.
AB  - Soy sauce materials of soybean meal and wheat bran were evaluated in solid-state
      (koji) fermentation (SSF) and submerged fermentation (SmF) by Aspergillus oryzae.
      Proteinase production in SSF (2331 +/- 39 U g-1) was about 4.9 times higher than
      that in SmF (477 +/- 13 U g-1), and glycoside hydrolase was approximately 2 times
      higher in SSF than that in SmF. In addition, protein expression of iTRAQ analysis
      deepens our understanding of the secreting mechanism. Abundant proteinases
      (dipeptidase, dipeptidyl aminopeptidase, puromycin-sensitive aminopeptidase, Xaa
      pro aminopeptidase, neutral protease 2 and leucine aminopeptidase 2), along with
      the glycoside hydrolase (glycoamylase, glucosidase and beta-xylanase) were
      secreted at the late stage of SSF, but tripeptidyl peptidase sed 2 was proposed
      as an indispensable protease in SmF or the early stage of SSF. Several
      metabolites associated with the carbon flux and amino acid biosynthesis were
      proved to be regulated by the proteinase and glycoside hydrolase production.

PMID- 30236723
TI  - Identification and characterization of antioxidant peptides from hydrolysate of
      blue-spotted stingray and their stability against thermal, pH and simulated
      gastrointestinal digestion treatments.
AB  - This study was conducted to identify and characterize antioxidant peptides from
      the alcalase hydrolysate of the blue-spotted stingray. Purification steps guided
      by ABTS cation radical (ABTS+) scavenging assay and de novo peptide sequencing
      produced two peptides, WAFAPA (661.3224 Da) and MYPGLA (650.3098 Da). WAFAPA
      (EC50 = 12.6 uM) had stronger antioxidant activity than glutathione (EC50 = 13.7
      uM) and MYPGLA (EC50 = 19.8 uM). Synergism between WAFAPA and MYPGLA was
      detected. WAFAPA and MYPGLA surpassed carnosine in their ability to suppress H2O2
      induced lipid oxidation. The peptides protected plasmid DNA and proteins from
      Fenton's reagent-induced oxidative damage. Thermal (25-100  degrees C) and pH 3
      11 treatments did not alter antioxidant activity of the peptides. MYPGLA
      maintained its antioxidant activity after simulated gastrointestinal digestion,
      whereas WAFAPA showed a partial loss. The two peptides may have potential
      applications as functional food ingredients or nutraceuticals, whether used
      singly or in combination.

PMID- 30236724
TI  - Investigating lignin from Canna edulis ker residues induced activation of alpha
      amylase: Kinetics, interaction, and molecular docking.
AB  - The lignin isolated from C. edulis ker residues showed a significant activating
      effect on alpha-amylase. Further studies revealed that the isolated lignin formed
      a 1:1 complex with alpha-amylase through hydrogen bonding and quenched
      fluorescence of alpha-amylase with a static quenching procedure. Binding with
      lignin led to conformational and granular size changes of alpha-amylase. Two
      dimensional nuclear Overhauser spectroscopy (2D-NOESY) spectra suggested that OH
      in G units and beta-O-4 structure were the major binding sites of lignin on the
      alpha-amylase molecule. Molecular docking studies indicated that the binding
      residue on alpha-amylase for lignin was not the same as for chloride ions, and
      the major binding force was hydrogen bonding. Furthermore, the docking results
      also showed the structural change of lignin induced by alpha-amylase. Thus, this
      work provided a new insight into the interaction between lignin from Canna edulis
      ker residues and alpha-amylase, which may be beneficial to apply lignin in the
      food industry.

PMID- 30236725
TI  - Nitrogen availability modulates the effects of ocean acidification on biomass
      yield and food quality of a marine crop Pyropia yezoensis.
AB  - Pyropia yezoensis is an important marine crop in the world. We cultured it under
      two levels of partial pressure of carbon dioxide (pCO2) (408 (LC), 998 (HC)
      MUatm) and nitrate (30 (LN) and 500 (HN) MUmol L-1) to investigate the effect of
      ocean acidification on its growth and food quality under changing nitrogen
      supply. HC decreased growth rate of P. yezoensis under LN but did not affect it
      under HN. Phycoerythrin and phycocyanin were enhanced by HC, particularly at HN,
      which contributed to the darker color. HC stimulated the synthesis of sweat amino
      acids regardless of nitrate condition and umami amino acid only under LN. HN
      increased the content of umami amino acids regardless of pCO2 condition and sweet
      amino acids only under HC. Our findings indicate that future ocean acidification
      may reduce biomass yield of P. yezoensis but increase its color and flavor, which
      was regulated by nitrate availability.

PMID- 30236726
TI  - Simultaneous determination of tocols, gamma-oryzanols, phytosterols, squalene,
      cholecalciferol and phylloquinone in rice bran and vegetable oil samples.
AB  - In this study, a simultaneous analytical method of tocols, gamma-oryzanols,
      phytosterols, squalene, cholecalciferol and phylloquinone were developed using
      HPLC-DAD-FLD. The developed method allowed the quantification of 18 compounds in
      30 min. Method validation showed linearity of calibration curves (alpha = 0.05).
      RSD of intra-day, inter-day and inter-laboratory precision were less than 4.88%.
      The limit of detections (LODs) and limit of quantifications (LOQs) were low
      (0.009-2.166 MUg g-1) with recoveries around 96.0-102.9%. Results derived from
      the established method demonstrated a wide variation of detected compounds in
      rice bran and vegetable oil samples (22.4-1774.6 MUg g-1 tocols, ND-26484 MUg g-1
      gamma-oryzanols, ND-12655 MUg g-1 phytosterols, ND-3189 MUg g-1 squalene, ND
      105.3 MUg g-1 cholecalciferol, and ND-54.4 MUg g-1 phylloquinone). Thus, the
      developed HPLC-DAD-FLD method is a powerful analytical tool for the above
      mentioned compounds useful in food and pharmaceutical application.

PMID- 30236727
TI  - Characterization of chemical compounds susceptible to be extracted from cork by
      the wine using GC-MS and 1H NMR metabolomic approaches.
AB  - This work presents a metabolomics study of cork by gas chromatography-mass
      spectrometry (GC-MS) and 1H nuclear magnetic resonance (NMR) spectroscopy to
      characterize compounds susceptible to be extracted from cork by the wine in an
      attempt to find a relationship between the content of these compounds and the
      geographical origin of cork. Cork from eleven geographical regions was studied,
      five from Portugal and six from Spain. Unsupervised pattern recognition
      techniques unveiled three main clusters of regions according to their chemical
      similarity but not related with geographical proximity. Nineteen compounds were
      found to be responsible for the clusters, including terpenes (trans-squalene,
      friedelin, camphene, trans-3-pinanone, 1-terpinen-4-ol, two sesquiterpenes),
      polyphenols (vescalagin, castalagin), among others (pyrogallol, glucosan, sitost
      4-en-3-one, o-cymene, quinic acid, five unknowns). These preliminary results
      unveiled the potential for a more efficient selection of cork planks for stoppers
      production based on the compounds susceptible to be extracted from cork by the
      wine.

PMID- 30236728
TI  - Characterization of chemical, molecular, thermal and rheological properties of
      medlar pectin extracted at optimum conditions as determined by Box-Behnken and
      ANFIS models.
AB  - In this work, response surface methodology and adaptive neuro-fuzzy inference
      system approaches were used to predict and model effect of extraction conditions
      of pectin from medlar fruit (Mespilus germanica L.). The pectin extracted at
      optimized conditions (89  degrees C, 4.83 h and 4.2 pH) could be classified as
      high methoxyl pectin. Sugar composition analysis showed that pectin was mainly
      composed of D-galacturonic acid, L-arabinose, L-rhamnose, D-galactose and D
      glucose. Fourier Transform Infrared Spectroscopy, RAMAN and nuclear magnetic
      resonance spectra confirmed molecular structure, revealing presence of D
      galacturonic acid backbone. X-ray diffraction patterns revealed an amorphous
      structure. Differential scanning calorimetry showed endothermic (123  degrees C)
      and exothermic peaks (192  degrees C). Thermogravimetric analysis revealed three
      decomposition regions, 50-225  degrees C, 225-400  degrees C and 400-600  degrees
      C. Steady and dynamic shear analyses revealed that pectin had a pseudo-plastic
      behavior with storage (G') and loss (G") modulus increasing with increment in
      frequency, indicating viscoelastic structure more predominantly elastic than
      viscous.

PMID- 30236729
TI  - Pistachio green hull pectin: Optimization of microwave-assisted extraction and
      evaluation of its physicochemical, structural and functional properties.
AB  - The optimal microwave-assisted extraction conditions of pistachio green hull
      (PGH) pectin (extraction yield of 18.13%) were in microwave power of 700 W,
      irradiation time of 165 s, and pH of 1.5. The physico-chemical, structural and
      functional properties of pectin was examined and the results showed that PGH
      pectin under optimum conditions was low methoxyl (about 12.1%) with molecular
      weight of 1.659 kg/mol, emulsifying activity of 58.3%, total phenolic content of
      18.18 mg GalAE/g pectin and good surface activity (46.23 and 49.75 mN/m at 0.1
      and 0.5% w/v). Also, high performance liquid chromatography analysis illustrated
      that the pectin is including galacturonic acid (66.0%), arabinose (26.2%),
      galactose (3.7%), rhamnose (2.7%) and xylose (1.0%). In addition, 1H NMR and FTIR
      spectrums confirmed the presence of pectin in obtained supenatnt. Surface
      morphology analysis and X-ray diffraction pattern showed that PGH pectin had a
      rough surface with crystalline structure.

PMID- 30236730
TI  - Winegrapes dehydration under ozone-enriched atmosphere: Influence on berry skin
      phenols release, cell wall composition and mechanical properties.
AB  - Gaseous ozone has been recently proposed as sanitizing agent to control mycobiota
      on grapes. The aim of this work was to evaluate the impact of ozone treatment
      during winegrapes dehydration (10 and 20% weight loss) on the content of phenolic
      compounds after treatment and their extractability during simulated maceration.
      The results showed that the ozone effect depends on the profile and content of
      anthocyanins and flavanols. For varieties characterized by prevalence of di
      substituted anthocyanins and high flavanol contents, no significant differences
      were observed in phenolic compounds contents, but lower anthocyanin
      extractability was found. Instead, for varieties rich in anthocyanins and with a
      tri-substituted prevalent profile, lower anthocyanin contents were found at 20%
      WL, but their extractability was significantly increased. Using multivariate
      analysis, the extractability was correlated with skin cell wall composition and
      mechanical properties. Proteins, non-cellulosic glucose and total phenols
      contributed mainly to explain phenolic compounds extractability in withered
      grapes.

PMID- 30236731
TI  - Effects of high hydrostatic pressure on quality changes of blends with low
      protein wheat and oat flour and derivative foods.
AB  - This study aimed to investigate the effect of high hydrostatic pressure (HHP) on
      the physicochemical characteristics of blended low-protein wheat (LW) and oat
      flour. Additionally, quality changes in noodles made from blends treated with HHP
      were investigated. Crude protein and fiber contents of LW were not affected by
      HHP; however, those of blends were significantly higher than those of LW (p <
      0.05). Water-holding capacity (WHC) of blends increased with HHP treatment. The
      peak viscosity of LW did not differ significantly because of HHP, and the peak
      and final viscosities of blends increased upon oat flour addition. The hardness,
      gumminess, chewiness of noodles made using LW improved with the addition of oat
      flour combined with HHP. The results indicated that the use of blends containing
      LW and oat flour as well as HHP treatment improved the quality and properties of
      noodles made using LW.

PMID- 30236732
TI  - Ion mobility spectrometry coupled to gas chromatography: A rapid tool to assess
      eggs freshness.
AB  - Egg products freshness is a crucial problem for the production of safe and high
      quality food. Ion Mobility Spectrometry (IMS) coupled to Gas Chromatography (GC),
      provides a rapid, sensitive, cost-effective tool for the detection of freshness
      issues. A chemometric model was created recording the volatile fingerprints of
      the different egg products batches, analyzed as fresh, then left at room
      temperature and daily controlled: 97% was correctly predicted by the model.
      Beside this, a selection of chemical marker compounds, coherently related with
      eggs thermal degradation processes, was also identified through the exploitation
      of Solid-Phase Micro Extraction Gas Chromatography (SPME-GC-MS) technique and
      associated to the parallel IMS volatile fingerprinting. The GC-IMS system was
      successfully challenged with the analysis of mixtures in which the predominant
      component was fresh egg product and different aged eggs were progressively added
      as adulterants, certifying the reliability of the method also for the detection
      of sharper fraudulent activities.

PMID- 30236733
TI  - Molecular docking and simulation of the synergistic effect between umami
      peptides, monosodium glutamate and taste receptor T1R1/T1R3.
AB  - In order to investigate the synergistic effect between umami peptides, monosodium
      glutamate (MSG) and the taste receptor T1R1/T1R3, a novel bivariate model was
      created based on our previous work. The results showed three specific changes
      upon the addition of MSG between umami peptides and T1R1/T1R3, in terms of energy
      and conformation. First, the addition of MSG enlarged the size of the binding
      cavity of T1R3 from 534.125 A3 to 1135.75 A3. Second, the addition of MSG caused
      small peptides to bind with T1R3, with the lowest docking energy and docking
      interaction energy, -77.2295 and -60.7146 kcal/mol respectively. Third, five
      binding residues ,including Glu-429, Gln-302, Gly-304, Try-107 and His-364,
      increased which play critical roles in hydrogen bonding. They are consistent with
      the results of electronic tongue and facilitate better understanding of the
      synergism. Furthermore, novel umami and umami-enhanced compounds could be
      discovered, based on the use of the novel bivariate model.

PMID- 30236734
TI  - Galangin inhibits alpha-glucosidase activity and formation of non-enzymatic
      glycation products.
AB  - Inhibition of alpha-glucosidase and non-enzymatic glycation is considered as an
      effective approach to treat type 2 diabetes. Herein, multispectroscopic
      techniques and molecular docking analysis were used to investigate the inhibition
      of galangin on alpha-glucosidase and non-enzymatic glycation. Galangin showed a
      reversible inhibition on alpha-glucosidase activity in a mixed-type manner
      through a monophasic kinetic process, and induced the fluorescence quenching and
      conformational changes of alpha-glucosidase by forming alpha-glucosidase
      galgangin complex. Molecular docking revealed that galangin primarily interacted
      with the amino acid residues within the active site of alpha-glucosidase, which
      may prevent the entrance of substrate resulting in a decrease in catalytic
      efficiency of alpha-glucosidase. Moreover, galangin moderately inhibited the
      formation of intermediates of non-enzymatic glycation, fructosamine and alpha
      dicarbonyl compounds and strongly inhibited the formation of advanced glycation
      end products.

PMID- 30236735
TI  - Improved stability, epithelial permeability and cellular antioxidant activity of
      beta-carotene via encapsulation by self-assembled alpha-lactalbumin micelles.
AB  - The low aqueous solubility, stability and bioavailability of hydrophobic
      bioactive compounds, such as beta-carotene (beta-c), greatly hinder their
      application in foods. Nanocarriers could overcome this problem by facilitating
      the delivery of the functional ingredients. We prepared lactalbumin (alpha-lac)
      micelles by partial enzymatic hydrolysis in aqueous solution. beta-c can be
      incorporated into the cores of these micelles via hydrophobic interactions. The
      aqueous solubility and stability under 60  degrees C heating or UV light
      irradiation of encapsulated beta-c improved significantly compared with free beta
      c. Moreover, it had an increased cellular uptake (3 times) and transmembrane
      permeability (13 times) in a Caco-2 cell monolayer model. It suggested that alpha
      lac micelle-encapsulated beta-c had an enhanced cellular absorption and transport
      efficiency. Encapsulated beta-c also exhibited an enhanced cellular anti-oxidant
      activity (CAA) compared with free beta-c. This work demonstrates that alpha-lac
      micelles showed a great potential for delivery of hydrophobic bioactive compounds
      in foods.

PMID- 30236736
TI  - Discovery and quantification of bioactive peptides in fermented cucumber by
      direct analysis IR-MALDESI mass spectrometry and LC-QQQ-MS.
AB  - Bioactive peptides have been identified in lactic acid bacteria fermented foods
      including cultured milk, sourdough, and cured meats; however, their presence has
      not been investigated in fermented vegetables. In this study, infrared, matrix
      assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry
      (MS) was employed to identify bioactive peptides in fermented cucumber. Natural
      and starter culture fermented cucumbers were prepared in triplicate in sodium
      chloride brines and compared to acidified cucumbers. Putative matches of known
      food-derived bioactive peptides were identified by direct analysis using IR
      MALDESI-MS. Peptides were confirmed by IR-MALDESI MS/MS and quantified by LC
      MS/MS. Three angiotensin converting enzyme (ACE) inhibitory peptides, IPP (0.42
      0.49 mg/kg), LPP (0.30-0.33 mg/kg), and VPP (0.32-0.35 mg/kg) were formed in
      fermented cucumbers. A fourth ACE inhibitory peptide, KP (0.93-1.5 mg/kg), was
      enhanced 3-5 fold in fermented cucumbers compared with acidified cucumbers. This
      work demonstrates that lactic acid bacteria fermentation can enhance bioactive
      peptide content in vegetables.

PMID- 30236737
TI  - An in vitro and in silico study on the antioxidant and cell culture-based study
      on the chemoprotective activities of fish muscle protein hydrolysates obtained
      from European seabass and gilthead seabream.
AB  - European seabass (Dicentrarchus labrax, Linnaeus, 1758) (L) and gilthead seabream
      (Sparus aurata, Linnaeus, 1758) (C) muscles were hydrolysated by Alcalase (Lalc,
      Calc) and Chymotrypsin (Lch, Cch) then hydrolysates were examined and their
      peptide profiles obtained. A total of 765, 794, 132 and 232 peptides were
      identified in Calc, Lalc, Cch and Lch, respectively. Although, Lch and Cch were
      expected to have more antioxidant capacity because of their peptide profiles,
      Alcalase hydrolysates observed in vitro, were slightly higher (TEAC assay for
      Calc: 848.11 +/- 60.78 MUmol TE/g protein). Maximum inhibition of oxidative
      stress was determined for Lalc (12.8% +/- 4.5%) in MDCK1 cell lines. Highest
      proliferative capacity observed for Calc (147.0% +/- 3.1%) at MTT assay in MDCK1
      cell culture. Lch showed the highest chemopreventive effect with a 40-60%
      decrease for human colon adenocarcinoma cell line HT-29. This research points out
      the importance of aquatic sources as raw materials for peptide researches.

PMID- 30236738
TI  - Comparison of the adsorption behaviour of catechin onto cellulose and pectin.
AB  - The adsorption behaviour of catechin onto cellulose and pectin was compared. The
      adsorption of catechin onto the two fibres involved an initial fast adsorption
      phase followed by a slower adsorption as the sites became saturated and the
      systems moved towards equilibrium. The adsorption capacity of pectin for catechin
      (20.71 +/- 2.24 mg/g) was significantly greater than that of cellulose (2.41 +/-
      0.05 mg/g) after equilibration for 24 h at 37  degrees C. The Langmuir and
      Freundlich models were applied to obtain the quantitative information about the
      adsorption of catechins to pectin and cellulose. Thermodynamic data derived from
      the isothermal adsorption carried out at the temperatures of 27  degrees C, 32 
      degrees C, 37  degrees C and 42  degrees C suggested that the adsorption was
      spontaneous and the binding was driven predominantly by physisorption.
      Fluorescence experiments confirmed the adsorption of catechins onto cellulose and
      pectin. The results showed that catechin adsorption capacity and adsorption
      mechanism were different for pectin and cellulose.

PMID- 30236739
TI  - Immobilization of Rhizomucor miehei lipase onto the organic functionalized SBA
      15: Their enzymatic properties and glycerolysis efficiencies for diacylglycerols
      production.
AB  - In this study, mesoporous silica SBA-15 was modified by organic functional groups
      through silanization. Series of organosilane compounds were grafted onto the SBA
      15, and the obtained functionalized carriers were then used to immobilize the
      lipase from Rhizomucor miehei (RML). The enzymatic properties of the obtained
      immobilized RML samples were evaluated, and the catalytic efficiencies in
      glycerolysis of triacylglycerols (TAG) reaction were studied. Compared with the
      parent SBA-15 immobilized RML, the organic modification gave a maximum
      improvement of enzymatic activity from 200.00 to 13211.11 U/g; in addition, TAG
      conversion and diacylglycerols (DAG) content increased from 21.28 to 84.24% and
      15.45 to 59.03% respectively. The organic modification also decreased the
      sensitivity of immobilized RML in extreme pH values and increased their
      thermostability.

PMID- 30236740
TI  - The impact of postharvest ultra-violet light irradiation on the thiol content of
      Sauvignon blanc grapes.
AB  - Sauvignon blanc grapes were exposed to an ultra-violet (UV) light source post
      hand harvest (whole bunches) or post-machine harvest. The thiol precursors S-3
      (hexan-1-ol)-l-cysteine (Cys-3MH) and S-3-(hexan-1-ol)-l-glutathione (GSH-3MH)
      were quantified in the juices before and after UV treatment. Results showed that
      irradiation of the grapes with UV light had little to no effect on the thiol
      precursors. Wines were fermented from the corresponding juices and 18 aroma
      compounds were quantified. Differences were found between UV treatments of the
      wines for 3-mercaptohexanol, hexan-1-ol, ethyl butanoate, ethyl hexanoate, ethyl
      octanoate and phenylethyl alcohol. However, these changes were not significant (p
      < 0.05) for both grape media trialled. Future studies involving larger sample
      sizes and replicate numbers should be completed in order to ascertain any changes
      in aroma chemistry as a result of UV light application to grapes postharvest.

PMID- 30236741
TI  - Oxidative stability of plant hydroalcoholic extracts assessed by EPR spin
      trapping under forced ageing conditions: A myrtle case study.
AB  - The oxidative stability of myrtle hydroalcoholic extracts was measured, over
      storage time, with the EPR spin trapping method under forced ageing conditions.
      The extracts were prepared with 150 and 300 g l-1 of berries and extraction media
      with ethanol ranging from 60 to 90%. Two radicals were detected: the PBN-1
      hydroxyethyl adduct and the tert-butyl aminoxyl radical. A dimensionless
      parameter (Omega) calculated on the basis of the lag time, the rate of formation
      and concentration of the radical species was used to estimate the extracts'
      oxidative stability. Omega was strongly influenced by the extraction medium,
      being lower in extracts with ethanol 60%, and by the time of storage. An inverse
      correlation was calculated between Omega and ellagic acid concentration, thus
      suggesting the role of this phenolic acid in the antioxidant properties of the
      extracts. The radical scavenging activity of the extracts against the hydroxyl
      radical was also measured.

PMID- 30236742
TI  - Optimization of ultrasonic assisted extraction of fatty acids from Aesculus
      hippocastanum fruit by response surface methodology.
AB  - The effectiveness of ultrasound-assisted extraction (UAE) of Aesculus
      hippocastanum fruit oil was investigated using methanol as a solvent. The study
      compared extraction yields using UAE and methanol with soxhlet. The effects of
      three extraction parameters, namely temperature, time and the ratio of solvent
      (volume) to plant material (weight) were optimized using both a Box-Behnken
      design (BBD) and response surface methodology (RSM). The highest extraction
      yields were obtained for UAE at 60  degrees C and 56.5 min with a ratio of
      solvent to plant material weight of 45:1. The extraction yield using UAE varied
      by 21.82% (w/ w) but was, regardless, significantly greater than Soxhlet
      extraction.

PMID- 30236743
TI  - Direct pentaplex PCR assay: An adjunct panel for meat species identification in
      Asian food products.
AB  - A direct pentaplex PCR assay was developed for the identification of meat from
      sources other than those declared on the packaging. Species-specific primers were
      designed, based on the mitochondrial cytochrome oxidase I (COI) gene. The assay
      amplified specific DNA fragments from dog (230 bp), duck (283 bp), buffalo (363
      bp), goat (396 bp), and sheep (477 bp). The proposed method is capable of
      identifying target species accurately and is reproducible, sensitive and robust
      for use with real-world foods and food products. In total, 26 of 117 meat and
      commercial food products tested were shown to contain DNA from species not
      declared on the label.

PMID- 30236745
TI  - Formation of allysine in beta-lactoglobulin and myofibrillar proteins by glyoxal
      and methylglyoxal: Impact on water-holding capacity and in vitro digestibility.
AB  - The ability of alpha-dicarbonyls, glyoxal (GO) and methyl-glyoxal (MGO) (2 M), to
      induce the formation of allysine in beta-lactoglubulin (LAC), and myofibrillar
      proteins (MP) (2 mg/mL) during incubation at 80  degrees C for 48 h, was studied.
      Both GO and MGO induced the formation of allysine in all tested proteins with GO
      being more reactive (23.8 and 8.6 nmoles/mg protein in LAC and MP respectively
      after 6 h) than MGO (2.6 and 3.1 nmoles/mg protein at the same sampling point).
      LAC seemed to be more susceptible to the glycation reactions than MP. The
      concentration of allysine decreased at 24 h along with a concomitant increase of
      advanced-glycation end-products suggesting that allysine may be involved in the
      formation of fluorescent adducts. The water-holding capacity and trypsin
      chymotrypsin digestibility of the proteins decreased during the incubation assay.
      The mechanisms by which alpha-dicarbonyls-mediated carbonylation likely
      influenced the impairment of such protein properties are thoroughly discussed.

PMID- 30236744
TI  - Production of hydroxyl radicals and their relationship with phenolic compounds in
      white wines.
AB  - Exposure of white wine to oxygen can cause detrimental effects, such as loss of
      sensorial characteristics. New antecedents, to the oxidation of wine, establish
      the importance of the formation of metallic complexes with compounds with
      adjacent hydroxyls. These complexes could reduce iron, promoting the formation of
      radicals through the Fenton reaction. The formation of hydroxyl radical (OH)
      induced by air was found in all 18 white wines analysed by electronic
      paramagnetic resonance (EPR) spectroscopy. The variation in the OH production was
      related to the phenolic composition of the wines. The amount of these radicals
      was linearly related to 5 phenolic compounds (caffeic acid, protocatechuic acid,
      p-coumaric acid, gentisic acid and syringic acid). Therefore, in this study, the
      relationship between certain phenolic compounds and the induction and
      amplification of the OH production was established and was postulated to be a
      chemical oxidation pathway to the Fenton reaction.

PMID- 30236746
TI  - Design, synthesis and characterization of tracers and development of a
      fluorescence polarization immunoassay for the rapid detection of ractopamine in
      pork.
AB  - In this study, 10 fluorescein-labeled ractopamine (RAC) derivatives (tracers)
      were synthesized and characterized to develop a rapid fluorescence polarization
      immunoassay (FPIA) for the detection of RAC in pork, using previously produced
      RAC polyclonal antibodies. The effect of the tracer structure on the sensitivity
      of the FPIA was investigated. The specificity of the FPIA was evaluated with 70
      beta-agonists and beta-blockers. The FPIA showed a limit of detection of 0.56 MUg
      kg-1 for RAC in pork, with recoveries ranging from 74.8% to 86.6% in spiked
      samples. The total analysis time, including sample pretreatment, was less than 1
      h. The FPIA was used to screen 150 commercial pork samples for RAC residues and
      the results were consistent with those of an enzyme-linked immunosorbent assay
      (ELISA) and ultra-high-performance liquid chromatography-tandem mass spectrometry
      (UPLC-MS/MS). Our results demonstrate that the FPIA developed here is a rapid,
      accurate, and sensitive screening method for RAC residues in pork.

PMID- 30236747
TI  - The effects of sucrose on the sol-gel phase transition and viscoelastic
      properties of potato starch solutions.
AB  - In this paper, starch pastes in the form of solutions and gels were investigated
      to determine viscoelastic properties and sol-gel phase transition temperatures
      using rheological methods. The gelatinization process was carried out at a
      temperature of 95  degrees C with the use of a pressureless starch cell with a
      stirrer. Starch pastes obtained were used to determine rheological properties
      under isothermal conditions (in the temperature range of 45-25  degrees C) by a
      cone-plate measurement system. The viscoelastic behavior of the tested medium was
      confirmed. The range of gelation temperatures was determined and the influence of
      several factors was discussed, e.g. the effect of sucrose addition and cooling
      rate on the phenomenon of sol-gel phase transition. In addition, mechanical
      properties of the obtained starch gel structures were determined using a
      fractional rheological model.

PMID- 30236748
TI  - Alterations in Temporal Summation of Pain and Conditioned Pain Modulation Across
      an Episode of Experimental Exercise-Induced Low Back Pain.
AB  - Persistent pain conditions, including low back pain (LBP), are often accompanied
      by alterations in pronociceptive and antinociceptive mechanisms, as quantified by
      temporal summation of pain (TSP) and conditioned pain modulation (CPM). It
      remains unclear whether altered pain sensitivity, CPM, and/or TSP are a
      consequence of pain presence or determine the degree of pain development.
      Pressure pain sensitivity, TSP, and CPM were assessed across an episode of
      exercise-induced LBP maintained for several days. Thirty healthy individuals
      participated in 3 experimental sessions: before (day 0), 2 days after fatiguing
      back muscle exercise with exercise-induced LBP present (day 2), and after pain
      resolution (day 7). Both handheld and cuff pressure-pain thresholds, along with
      TSP (10-cuff pain stimuli at .5 Hz) and CPM (cuff pain detection threshold prior
      versus during painful pressure conditioning) were assessed, alongside
      questionnaires pertaining to pain, disability, mood, sleep, menstruation,
      physical activity, and catastrophizing. The exercise-induced LBP model produced
      mild pain and disability, and reductions in pressure pain thresholds over both
      the lumbar and distant testing sites (p < .007). No pain-related changes were
      observed for TSP (p > .44) or CPM (p > .17). The baseline TSP was associated with
      the peak pain intensity of the exercise-induced LBP (p < .003). Perspective:
      Pressure-pain sensitivity was impacted by the presence of exercise-induced LBP,
      whereas TSP seemed to be more stable and was instead associated with the
      intensity of pain developed. No significant pain-related changes or associations
      were observed for CPM, suggesting this measure may have less usefulness in mild
      musculoskeletal pain conditions.

PMID- 30236749
TI  - Clinical, Patient-Reported, and Ultrasound Outcomes from an Open-Label, 12-week
      Observational Study of Certolizumab Pegol in Spanish Patients with Rheumatoid
      Arthritis with or without Prior Anti-TNF Exposure.
AB  - OBJECTIVES: To assess the effectiveness and safety of certolizumab pegol (CZP) in
      Spanish patients with RA. MATERIALS AND METHODS: SONAR (NCT01526434), a 12-week,
      open-label, prospective, observational, multicenter study. Patients with active
      RA for >=3 months, according to ACR criteria, were treated with CZP (400mg at
      Weeks 0, 2 and 4, then 200mg every 2 weeks). The primary effectiveness endpoint
      was change from baseline (CFB) in Health Assessment Questionnaire-Disability
      Index (HAQ-DI) at Week 12. Other assessments included DAS28(ESR), patient's
      assessment of arthritis pain (PtAAP-VAS) and Short Form 36-item Health Survey (SF
      36) physical component summary (PCS) and mental component summary (MCS). Joint
      inflammation was investigated using Power Doppler (PD) ultrasound (US), to detect
      effusion, synovial hypertrophy and synovial PD signal. PDUS outcomes assessed CFB
      to Week 12 in synovial hypertrophy, effusion and PD signal indices. RESULTS: A
      total of 77/80 enrolled patients received >=1 dose of CZP. The 12-week mean
      reduction from baseline (SD) was -0.6 (0.6) for HAQ-DI and -2.2 (1.5) for
      DAS28(ESR). PtAAP-VAS was reduced from baseline (mean [SD]: -36.8 [26.8]) and
      improvements in SF-36 PCS and SF-36 MCS were reported. Synovial hypertrophy,
      effusion and PD signal indices were reduced from baseline to Week 12. One death
      was reported during the study. CONCLUSIONS: Spanish patients with RA demonstrated
      improvements in clinical, PDUS and patient-reported outcomes over 12 weeks of CZP
      treatment. No new safety signals were identified, and the safety profile was in
      line with previous CZP studies. These results support previous clinical trial
      findings investigating CZP treatment for active RA.

PMID- 30236750
TI  - Transcatheter Valve Replacement for Right-sided Valve Disease in Congenital Heart
      Patients.
AB  - Pulmonary and/or tricuspid valve dysfunction is common among individuals with
      congenital heart disease, and surgical intervention often carries prohibitive
      risks. Transcatheter valve replacement (TVR) of the right-sided cardiac valves
      has become a viable treatment option over the past two decades, while continued
      technological development aims to broaden its applicability to an even larger
      portion of those with repaired congenital heart disease. To date, two
      transcatheter valves have been approved for use in patients with dysfunctional
      right ventricular to pulmonary artery conduits as well as those with failing
      pulmonic bioprosthetic valves, and are also used off-label in the "native" RVOT
      and within surgically repaired/replaced but failing tricuspid valves. TVR has
      demonstrated comparable safety and short-term outcomes to that of surgical valve
      replacement. This article aims to review current available devices, focusing on
      their safety, efficacy and on and off label usage, while briefly describing some
      of the emerging devices and novel procedural techniques that will likely lead to
      significant expansion of transcatheter treatment of right sided valve disease in
      the future.

PMID- 30236751
TI  - Long Term Consequences of the Fontan Procedure and How to Manage Them.
AB  - In 1971, Fontan and Baudet described a surgical technique for successful
      palliation of patients with tricuspid atresia. Subsequently, this technique has
      been applied to treat most forms of functional single ventricles and has become
      the current standard of care for long-term palliation of all patients with single
      ventricle congenital heart disease. Since 1971, the Fontan procedure has
      undergone several variations. These patients require lifelong management
      including a thorough knowledge of their anatomic substrate, hemodynamic status,
      management of rhythm and ventricular function along with multi organ evaluation.
      As these patients enter middle age, there is increasing awareness regarding the
      long-term complications and mortality. This review highlights the long-term
      outcomes of the Fontan procedure and management of late sequelae.

PMID- 30236753
TI  - Letter to the editor.
AB  - Today, find a good and effective drug for improving the incidence of Alzheimer
      disease (AD) is a major concern among scientists. Many researchers have recently
      targeted curcumin, a yellow powder from Curcuma longa, as the useful source of
      anti-Alzheimer agent. Though this compound widely used since ancient times as
      food color and/or additive, currently some researchers believed that this
      compound can treat AD-affected brains. However, the accurate mechanism of action
      of curcumin in the treatment of AD is obscure. In the recently published paper by
      Bijari et al. this compound (or pigment) considered as the functional food to
      cure AD. Their paper aimed to prove evident for the anti-AD activity of curcumin,
      but I found several errors with this paper that should be corrected by the
      authors. All of my queries and concerns are listed in the main text of this
      letter.

PMID- 30236752
TI  - The Importance of School-based Healthy Living Initiatives: Introducing the Health
      and Wellness Academy Concept.
AB  - Over the last 15 years, the number of school and community based health
      intervention programs in the United States has grown. Many of these programs aim
      to prevent non-communicable chronic disease diagnoses (e.g., obesity,
      cardiovascular disease and type-2 diabetes). The Department of Physical Therapy
      in the College of Applied Health Sciences (CAHS) at the University of Illinois at
      Chicago (UIC) created a school-based wellness program (SBWP) that focuses on
      nutrition and physical activity, providing tailored experiences that motivate
      adolescents to make healthier lifestyle choices. The SBWP began as a camp for
      children in the surrounding neighborhoods and implemented healthy living
      practices utilizing students from Departments in the CAHS. From this camp, the
      Health and Wellness Academy (HWA) evolved. This paper provides a review of school
      based initiatives and introduces the UIC HWA, an innovative and reproducible
      approach that can bring positive environmental change by improving health
      outcomes for children and their families.

PMID- 30236754
TI  - Evaluation of quaternary ammonium chitosan derivatives differing in the length of
      alkyl side-chain: Synthesis and antifungal activity.
AB  - Chemical modification is one of the prominent methods used to improve the water
      solubility and bioactivity of chitosan. In this paper, a series of quaternary
      ammonium chitosan derivatives based on 6-O-chloroacetylated chitosan (CAClC) were
      successfully designed and synthesized. Detailed structural characterization was
      carried out by means of FT-IR, 1H NMR spectroscopy, and elemental analysis.
      Furthermore, the antifungal activity against Botrytis cinerea, Gibberella zeae,
      and Physalospora piricola Nose was estimated using in vitro hypha measurements.
      Most of the quaternary ammonium chitosan derivatives showed an inhibitory index
      of >90% at 1.0 mg/mL and exhibited enhanced antifungal activity when compared to
      chitosan. On one hand, the higher density of positive charge contributed to the
      antifungal action. In addition, the inhibitory activity decreased roughly in the
      order of TriM [(CH3)3] > TriE [(CH2CH3)3] > TriP [(CH2CH2CH3)3] > TriB
      [(CH2CH2CH2CH3)3]; NNTE [(CH3)2(CH2CH3)] > NNTB [(CH3)2(CH2CH2CH2CH3)] > NNTK
      [(CH3)2((CH2)9CH3)] at 1.0 mg/mL. The antifungal properties of all the quaternary
      ammonium chitosan derivatives against the targeted fungi decreased upon
      increasing the alkyl chain length.

PMID- 30236756
TI  - Fabrication of tetraethylenepentamine functionalized alginate beads for
      adsorptive removal of Cr (VI) from aqueous solutions.
AB  - In this study, an innovative adsorbent based on tetraethylenepentamine (TEPA)
      functionalized alginate (Alg) beads (TEPA-Alg) was developed for the adsorptive
      removal of Cr (VI) from aqueous solutions. Chemical modification of alginate
      surface was carried out using p-benzoquinone (PBQ) as a coupling agent followed
      by functionalization with TEPA. The prepared functionalized beads were
      characterized using FTIR, TGA, SEM, and XPS tools. Results showed that the ion
      exchange capacity (IEC) significantly increased from 6.34 to 10.32 meq g-1 with
      increasing TEPA concentration up to 0.05 M. Furthermore, removal (%) of Cr (VI)
      increased gradually from 38 to 86% with rising TEPA concentration from 0.0125 M
      to 0.05 M. While only 22% was recorded using native alginate beads. The gained
      equilibrium data were fitted to Langmuir isotherm model with maximum adsorption
      capacity ~ 77 mg/g and the adsorption kinetics were well-expressed by pseudo
      first-order model. Reusability studies showed good adsorption properties after 5
      consecutive cycles. Results achieved by this study imply that the prepared
      functionalized TEPA-Alg beads could be efficiently utilized for the removing Cr
      (VI) ions from their aqueous solutions.

PMID- 30236755
TI  - Purification and characterization of catechol oxidase from Tadela (Phoenix
      dactylifera L.) date fruit.
AB  - Catechol oxidase (PPO) was extracted and purified from Tadela (Phoenix
      dactylifera L.) date fruit, by a procedure that included (NH4)2SO4 precipitation
      followed by dialysis, Q-Sepharose bb ion-exchange chromatography and HPLC gel
      filtration chromatography. Some of its biochemical characteristics were studied.
      The purification rate and the yield were 80% and 20%, respectively. The Tadela
      date fruit catechol oxidase exhibited a molecular weight of 90 kDa using SDS
      PAGE. The catechol oxidase showed only o-diphenolase and triphenolase activities
      while no monophenolase activity was detected. A better affinity was observed
      using catechol as substrate (Km = 35 mM) with thus, a higher Vmax/Km ratio (80
      U/mM.mL). This enzyme is thermostable in the temperature range (30-60  degrees C)
      with optimum activity in acidic range of pH. Four inhibitors were used for the
      control of enzymatic browning, of which sodium metabisulfite was the most potent
      (IC50 = 0, 11 mM). The values of KI and mechanism of inhibition were also
      determined. No significant change on enzyme activity was noticed in the presence
      of metal ion and detergents. Therefore, thermal inactivation was studied in the
      temperature range between 60 and 80  degrees C using catechol as substrate. Their
      kinetic (K, D, t1/2, Zt, Ea) and thermodynamic (DeltaH, DeltaG and DeltaS)
      parameters were also estimated.

PMID- 30236757
TI  - Comparison of structures of walnut protein fractions obtained through reverse
      micelles and alkaline extraction with isoelectric precipitation.
AB  - The effects of different extraction methods on the contents of disulfide (SS) and
      sulfhydryl (SH) and secondary structure of albumin, globulin, prolamin and
      glutelin fractions from walnut proteins were evaluated. By comparison with the
      changing trend for four protein fractions from alkali extraction with isoelectric
      precipitation (AEIP), the SH contents of globulin, prolamin and glutelin
      fractions from the reverse micelles (RMs) significantly increased (p < 0.05), but
      decreased in the albumin faction. The SS bond contents of albumin, globulin and
      glutelin fractions obtained by two extraction methods were similar, except that
      the SS bond content in prolamin obtained through RMs increased by 2.57%. Fourier
      transform infrared (FTIR) results showed that the proportions of alpha-helix in
      globulin, beta-sheet structure in prolamin, unordered structure in globulin,
      prolamin and glutein, turn structure in albumin, prolamin and glutelin by RMs
      were higher than those by AEIP. Scanning electron microscopy showed that the
      reverse micelle extraction could affect the surface structures of four protein
      fractions.

PMID- 30236758
TI  - A cold-water soluble polysaccharide isolated from Grifola frondosa induces the
      apoptosis of HepG2 cells through mitochondrial passway.
AB  - Grifola frondosa is a widely eaten and medicinal fungus. In this study, we
      extracted a cold-water-soluble polysaccharide from Grifola frondosa (cGFP) and
      investigated its effects on the proliferation and apoptosis of human hepatoma
      HepG2 cells. MTT assay showed that cGFP induced apoptosis of HepG2 cells in a
      dose-dependent manner. Flow cytometry analysis showed that cGFP induced apoptosis
      in HepG2 cells through S phase arrest. The distribution of cells at different
      apoptotic stages was determined by Annexin V-FITC and Propidium Iodide (PI)
      staining. Scanning electron microscopy (SEM) results indicated that cGFP induced
      typical apoptotic morphological features in HepG2. Mitochondrial membrane
      potential was reduced according to the screening of JC-1 staining. And western
      blot analysis of Bax, Bcl-2, cytochrome C (Cyto-c), caspase-3, and caspase-9
      further demonstrated that the cGFP-induced apoptosis effect functioned through
      the mitochondrial pathway. Further analysis by qRT-PCR showed that Bax expression
      increased and Bcl-2 expression decreased. These findings suggested that cGFP
      could inhibit the proliferation of HepG2 cells and induce apoptosis mainly
      through the intrinsic activation mitochondrial pathway.

PMID- 30236760
TI  - Higher plasma leptin and lower C-peptide levels are associated with depression: A
      cross-sectional study.
AB  - BACKGROUND: Depression is a seriously disabling public health problem with very
      high world-wide prevalence. This study examined cross-sectional association
      between depression and both inflammatory markers and laboratory data involved in
      metabolic disturbance among Japanese subjects. METHODS: This cross-sectional
      study is a secondly analysis for the data of the Iwaki Health Promotion Project
      2014 (1167 subjects). Plasma inflammatory markers and laboratory metabolic data
      involved were used. Center for Epidemiologic Studies Depression Scale (CES-D) was
      used to assess the prevalence and severity of depressive symptoms. Participants
      with CES-D scores >= 16 were assigned to the 'Depression' group (Group D).
      Differences between group Non-depression (ND) and D were estimated using chi2
      test or Fisher's exact test for categorical variables and Student's t-test or
      Mann-Whitney test for continuous variables. Multivariate logistic regression
      analysis was also used to identify characteristics, co-morbidities, conditions
      and laboratory data associated with depression after adjusting for possible
      confounding factors. RESULTS: There were significant differences in sex, age,
      blood pressure, interleukin (IL)-6, fasting blood sugar (FBS), hemoglobin A1c
      (HbA1c), and cortisol level using univariate analysis between the two groups.
      However, multivariate logistic regression analysis indicated that lower age,
      lower C-peptide, and higher leptin were associated with the depression.
      CONCLUSION: This study showed that higher plasma leptin and lower C-peptide
      levels were significantly associated with depressive symptoms. No significant
      association was found between plasma inflammatory markers and depressive symptoms
      after adjusting for possible confounding factors.

PMID- 30236761
TI  - Maternal suppplementation with conjugated linoleic acid reduce anxiety and lipid
      peroxidation in the offspring brain.
AB  - BACKGROUND: Maternal consumption of fatty acids can alter neuronal membrane
      function, synaptic connections, and protect the brain from alterations caused by
      disturbances such as lipid peroxidation and anxiety in the offspring. We aimed to
      investigate how the maternal consumption of conjugated linoleic acid (CLA)
      interferes in anxiety behavior of the offspring and cerebral lipid peroxidation.
      METHODS: Three groups were formed: control (CG) - diet without CLA; CLA1 - diet
      containing 1% of CLA; and CLA3 - diet containing 3% of CLA. These diets were
      offered to the mothers from the 7th day of gestation until the end of lactation.
      The following behavioral tests were used: Elevated plus maze (EPM), Open Field
      (OF) and Light-dark Box (LDB). Levels of malondialdehyde (MDA) and glutathione
      were measured in the offspring's brains. Data were analyzed by ANOVA followed by
      the Holm-Sidak post-test or the Kruskal-Wallis test (p < 0.05). RESULTS: CLA1 and
      CLA3 showed higher number of entries in the open arms and time spent in the
      central area in EPM, they translocated and ambulated more in the clear area of
      the LDB and presented more rearing in the OF compared to CG (p < 0.05); moreover,
      they presented higher concentration of glutathione and lower MDA in brain tissue
      (p < 0.05). LIMITATIONS: We evaluated the effect of maternal consumption of CLA
      on anxiety and lipid peroxidation in rats' offspring, but a similar study should
      be performed in humans. CONCLUSIONS: Maternal intake of CLA induced a decrease in
      the parameters of anxiety and cerebral lipid peroxidation in the offspring.

PMID- 30236762
TI  - Simvastatin therapy in adolescent mice attenuates HFD-induced depression-like
      behavior by reducing hippocampal neuroinflammation.
AB  - BACKGROUND: A high-fat diet (HFD)-induced obesity/hyperlipidemia is accompanied
      by hormonal and neurochemical changes that can be associated with depression.
      Emerging studies indicate that simvastatin (SMV, decreasing cholesterol levels)
      has therapeutic effects on neurological and neuropsychiatric diseases through
      hippocampal-dependent function. However, the studies on the HFD exposure in
      adolescent animals, which investigate the neuroprotective effects of SMV on the
      hippocampal morphology, serotonin (5-HT) system and inflammation, are limited.
      Hence, the aim of this study was to determine whether SMV attenuates HFD-induced
      major depressive disorders in adolescent animals and, more specifically, acts as
      an anti-neuroinflammatory response. METHODS: Twenty-four male C57BL/6 mice were
      fed a control (n = 8), HFD (n = 8) and HFD + SMV (n = 8) for 14 weeks. In HFD +
      SMV group, SMV (10 mg/kg) was administrated from the 10th week of HFD feeding.
      The open field test (OFT) and the tail suspension test (TST) were used to examine
      the effect of SMV on behavioral performance. HE and Nissl staining were conducted
      to detect hippocampal morphology and neural survival. Expression of the
      inflammatory cytokine genes was assayed by quantitative polymerase chain reaction
      (Q-PCR). RESULTS: Firstly, alterations in lipid parameters were minimized after
      SMV treatment. HFD-induced depression-like behavior, which was evidenced by an
      increase in immobility time in TST along with considerable decrease in locomotion
      activity, was significantly attenuated by SMV therapy for 4 weeks. Additionally,
      SMV could reduce HFD-induced structural abnormality, neuronal injury,
      serotonergic system disturbance and pro-inflammatory cytokine over-expression in
      the hippocampus. Neuroimmunological changes in central hippocampus displayed a
      similar characteristic (only IL-1beta, IL-6, TNF-alpha) with that in periphery
      spleen, whereas they appeared in an entirely opposite trend with that in cerebral
      cortex. CONCLUSION: Our results suggest that SMV may be a promising treatment for
      HFD-induced depression-like behavior during adolescent period through brain
      region-specific neuroninflammatory mechanisms.

PMID- 30236759
TI  - White matter abnormalities predict residual negative self-referential thinking
      following treatment of late-life depression with escitalopram: A preliminary
      study.
AB  - BACKGROUND: Negative self-referential thinking is a common symptom of depression
      associated with poor treatment response. In late-life depression, white matter
      abnormalities may contribute to negative self-referential thoughts following
      antidepressant treatment. We investigated the association of fractional
      anisotropy (FA) in select regions of the negative valence system (NVS) with
      residual negative self-referential thoughts following treatment with escitalopram
      for late-life depression. METHODS: The participants were older adults with major
      depression and psychiatrically normal controls. Depressed participants received
      12 weeks of treatment with escitalopram. To assess self-referential thinking,
      participants completed a Trait Adjective Task at baseline and at week 12.
      Baseline MRI scans included a diffusion imaging sequence for FA analyses.
      RESULTS: Participants with late-life depression differed from controls on all
      performance measures of the Trait Adjective Task at baseline and at 12 weeks.
      Depressed participants endorsed fewer negative personality traits and more
      positive personality traits at week 12 compared to baseline. Lower FA in the
      dorsal anterior cingulate and in the uncinate fasciculus in depressed
      participants was correlated with residual negative self-referential thinking
      (e.g., more endorsed negative adjectives, fewer rejected negative adjectives) at
      treatment end. LIMITATIONS: The sample size is modest so the findings are
      preliminary. FA analyses were restricted to predetermined regions. CONCLUSIONS:
      Negative self-referential thinking improved in depressed older adults following
      12 weeks of treatment with escitalopram. Baseline FA in select white matter
      regions of the NVS was associated with residual negative self-referential
      thinking. These findings may help identify treatment targets for residual
      negative self-referential thoughts.

PMID- 30236764
TI  - Bugs in inflammatory bowel disease - A questionable therapy.

PMID- 30236763
TI  - Sema 3A as a biomarker of the activated mTOR pathway during hexavalent chromium
      induced acute kidney injury.
AB  - Semaphorin 3A (sema 3A) is one of a class of secretory proteins belonging to a
      family of axon-directed factors found in podocytes, distal tubules, and
      collecting tubes of the kidney. It is considered to be a potential target
      molecule involved in the mammalian target of the rapamycin (mTOR) pathway in
      renal injury or renal diseases, but it has an unknown role in the course of
      hexavalent chromium-Cr(VI) induced nephrotoxicity. In the present study, an acute
      kidney injury (AKI) model in rats or cultured tubular epithelial HK-2 cells was
      employed for Cr(VI) exposure alone or in combination with rapamycin (Rap) or N
      acetyl-l-cysteine (NAC) or recombinant sema 3A. The methods of histopathology,
      biochemics, and western blotting were applied to evaluate tubular injury and the
      role of sema 3A. The results showed that a significant increase of urinary sema
      3A indicates an early occurrence of AKI exposed to Cr(VI), accompanied with a
      significant increase of tubular injury score and phosphorylated mTOR proteins.
      Further, Cr(VI) treatment, in combination with pretreatment of the mTOR pathway
      inhibitor, Rap, showed a considerably stronger protective effect of Rap in
      protecting against Cr(VI)-induced nephrotoxicity than that seen with the free
      radical scavenger NAC, highlighting the dominant renal protective role of the
      mTOR pathway in inhibiting toxicity by downregulating the expressed levels of
      sema 3A in renal tissue. This study has demonstrated that an increased expression
      of sema 3A occurs in Cr(VI)-induced AKI resulting from activation of the mTOR
      pathway, and that inhibition of this pathway has been shown to decrease the
      severity of the toxicity. In conclusion, this study has shown that increased
      urinary sema 3A is indicative of an activated mTOR pathway and is a valuable
      biomarker of the early AKI induced by Cr(VI) exposure.

PMID- 30236765
TI  - Deficiency of micronutrients in patients affected by chronic atrophic autoimmune
      gastritis: A single-institution observational study.
AB  - BACKGROUND: Chronic atrophic autoimmune gastritis (CAAG) leads to vitamin B12
      deficiency, but other micronutrient deficiencies are largely understudied. AIMS:
      To investigate the prevalence of micronutrient deficiencies in CAAG patients and
      their potential relationship with the grading of gastric atrophy or entero
      chromaffin-like cells hyperplasia or body mass index (BMI). METHODS: From 2005 to
      2016 a number of CAAG patients underwent regular follow-up with annual blood
      testing and upper gastrointestinal tract endoscopy every years. RESULTS: Out of
      the 122 CAAG patients checked (100 F; median age 65 years), 76 presented
      nutritional deficiencies, single in 24 and multiple in 52 cases: a deficiency of
      B12 and iron showed in 42 patients, 25-OH vitamin D lacked in 76 and folic acid
      in 6 cases. 25-OH vitamin D levels directly correlated with B12 levels and were
      significantly lower in patients with macronodular than in those with linear or
      micronodular hyperplasia. No significant correlation was observed between B12,
      folic acid or ferritin levels and BMI, blood gastrin levels, the grading of
      gastric atrophy or ECL cells hyperplasia. CONCLUSIONS: 25-OH vitamin D deficiency
      was the main one in CAAG patients: its correlation with B12 deficiency may
      indicate underlying shared pathogenic mechanisms, although further studies are
      needed to confirm this hypothesis.

PMID- 30236766
TI  - Right lobe split liver graft versus whole liver transplantation: A systematic
      review by updated traditional and cumulative meta-analysis.
AB  - INTRODUCTION: Advancements in surgical techniques and experience of donor
      recipient pairing has led to a wider use of right split liver grafts in adults.
      An update meta-analysis was conducted to compare right split liver graft (RSLG)
      and whole liver transplantation (WLT) using traditional and cumulative
      approaches. METHODS: Databases were searched for relevant articles over the
      previous 20 years (MEDLINE, Embase, Cochrane Library, and Google Scholar). Meta
      analyses were performed using both fixed and random effects models. Patient and
      graft survival were obtained using the inverse variance hazard ratio method.
      RESULTS: Donors were significantly younger in the RSLG group than in the WLT
      group (MD = -12.06 [-16.29 to -7.83]; P < .001). In addition, the model for end
      stage liver disease (MELD) score was significantly lower in the RSLG group than
      in the WLT group (MD = -2.45 [-4.61 to -.28]; P = .03). However, cold ischaemia
      time was significantly longer by 1 h in the RSLG group than in the WLT group (MD
      = 57 [20.63-92.73]; P = .002). Overall biliary, vascular, and outflow tract
      complications and hepatic artery thrombosis were significantly lower in the WLT
      group than in the RSLG group (odds ratio [OR] = 1.75 [1.35-2.27], P < .001; OR =
      1.91 [1.37-2.65], P = .006; Peto OR = 1.83 [1.19-2.82], P = .006; and Peto OR =
      2.07 [1.39-3.10], P = .004, respectively). However, no difference in patient and
      graft survival was noted between the two cohorts. CONCLUSIONS: Although the RSLG
      group had a higher postoperative complication rate than the WLT group, equal
      patient and graft survival benefits were observed.

PMID- 30236767
TI  - Analysis of endoscopic features for histologic discrepancies between biopsy and
      endoscopic submucosal dissection in gastric neoplasms: 10-year results.
AB  - BACKGROUND AND AIM: The histologic discrepancies between preoperative endoscopic
      forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) specimens
      sometimes confuse the endoscope operator. This study aimed to analyze the
      limitation of the biopsy-based diagnosis before ESD and to evaluate which factors
      affect the discordant pathologic results between EFB and ESD. METHODS: A total of
      1427 patients, who were diagnosed with gastric adenoma by EFB, were enrolled.
      Cancer confirmed on EFB was excluded (n = 513). We retrospectively reviewed cases
      and compared histologic diagnoses in the biopsy sample with the final diagnosis
      in the endoscopically resected specimen. RESULTS: The diagnosis was upgraded
      (from low-grade dysplasia to high-grade dysplasia or adenocarcinoma, or from high
      grade dysplasia to adenocarcinoma) in 328 cases (23.0%), concordant in 944
      (66.1%), and downgraded (from high-grade dysplasia to low-grade dysplasia or non
      neoplasia, or from low-grade dysplasia to non-neoplasia) in 155 (10.9%).
      Multivariate logistic regression analysis showed that surface ulceration and
      depressed lesions were associated with significant risk factors for upgrading.
      Age younger than 60 years and size <1 cm were associated with significant factors
      for downgrading. CONCLUSIONS: Careful endoscopic observation should consider
      size, ulceration, and depression to ensure accurate diagnosis when a gastric
      neoplasm is suspected.

PMID- 30236768
TI  - ACE I allele is associated with more severe portal hypertension in patients with
      liver cirrhosis: A pilot study.
AB  - BACKGROUND: In liver cirrhosis, the renin-angiotensin-aldosterone system is
      involved in the pathogenesis of portal hypertension. Its effector, angiotensin
      II, is generated by angiotensin-converting enzyme (ACE). Serum ACE levels are
      affected by I/D polymorphism of its gene, with alleles I and D being associated,
      respectively, with lesser and greater activity of the enzyme. In cirrhotic
      patients carrying the ACE I allele, an increased risk for gastro-oesophageal
      varices was observed. AIM: The aim of our study was to evaluate whether ACE I/D
      polymorphism influenced portal pressure. METHODS: Fifty-one consecutive cirrhotic
      patients were divided based on ACE genotype (DD, ID, and II). Kidney and liver
      function tests, upper endoscopy, and hepatic venous pressure gradient measurement
      (HVPG) were performed in all patients. RESULTS: The presence of the ACE I allele
      was associated with a higher HVPG value (18.7 +/- 6.4 vs 10.3 +/- 6.3 mmHg; P <
      .001), higher frequency of large gastrooesophageal varices (59.3% vs 25.0%; P <
      .05), and higher frequency of variceal bleeding (63.0% vs 29.2%; P < .05). No
      significant differences were found between patients with and those without the
      ACE I allele regarding Child-Pugh score, MELD score, ascites, and hepatic
      encephalopathy. CONCLUSION: ACE I/D polymorphism seems to influence the severity
      of portal hypertension and the risk of variceal bleeding in liver cirrhosis,
      regardless of the severity of liver disease.

PMID- 30236769
TI  - A novel C-terminal truncated mutation in hCDKL5 protein causing a severe West
      syndrome: Comparison with previous truncated mutations and genotype/phenotype
      correlation.
AB  - INTRODUCTION: West Syndrome is a severe epileptic encephalopathy characterized by
      epileptic spasms, hypsarrhythmia, and regression of psychomotor acquisitions
      beginning in the first year of life. ARX and CDKL5 genes were identified as
      linked to the most frequent genetic causes of West Syndrome. METHODS: The present
      study reports the clinical, molecular and bioinformatic investigation of the
      patient with severe West syndrome. RESULTS: Molecular analysis of the two
      candidate genes, i.e. ARX and CDKL5 showed the presence of a novel insertion
      c.2788insG in exon 19 of CDKL5 gene. This mutation causes changes in cis
      regulation elements of exon 19 splicing and in secondary pre-mRNA structure
      leading probably to inclusion of alternative exon 19 in hCDKL5_5 isoform for
      which foetal brain expression was recently confirmed. This insertion led also to
      a frameshift mutation and generated a premature stop codon (p.E930Gfs9X) in the C
      terminal domain and causing the lack of a part of the signal recognized by
      proteasome as well as the lack of peptidase I serine active site. Moreover, we
      review previously described, truncated mutations occurring in different regions
      of the C- terminal domain, and we compared the subcellular mutated protein
      localization and their resulting patients' phenotypes. CONCLUSIONS: The
      impairment of alternative splicing of exon 19 and the lack of a part of the
      proteasome signal due to c.2788insG mutation could disrupt the dynamic regulation
      of isoform levels especially hCDKL5_5 and hCDKL5_1 during pre and postnatal
      neurodevelopment and then could cause pathogenic phenotype. Signal peptidase I
      serine active site seems to modulate hCDKL5_5 movements between nucleus and
      cytoplasm. We noticed that the resulting phenotypes from truncated mutations
      among the C-terminal domain of hCDKL5 are almost similar and are always severe.

PMID- 30236770
TI  - NLRP3 inflammasome regulates Th17 differentiation in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Th17 has
      been shown to play am important role in the pathogenesis of RA. Accumulating data
      suggest the involvement of NLRP3 inflammasome in Th17 differentiation in
      autoimmune diseases. In the current study, we found that NLRP3 inflammasome is
      activated in CD4 T cells from RA patients. The activation of NLRP3 inflammasome
      was correlated with disease activities and IL-17A concentration in RA sera.
      Knockdown of NLRP3 suppressed Th17 differentiation. In addition, caspase-1 or IL
      1 receptor inhibitor inhibits Th17 differentiation significantly. Further, ROS
      production is increased in CD4 T cells from RA patients. The inhibition of ROS
      production decreased NLRP3 inflammasome activation and IL-1beta production in CD4
      T cells, leading to the suppression of Th17 differentiation. These findings
      suggest a pathogenic role of NLRP3 inflammasome in RA by promoting Th17 cell
      differentiation. NLRP3 inflammasome could be a potential therapeutic target for
      the treatment of RA.

PMID- 30236771
TI  - Residual iris retraction syndrome after artificial iris implantation.
AB  - PURPOSE: To evaluate the effect of an artificial iris implant on the remnant
      iris. DESIGN: Interventional case series METHODS: Setting: single-centre PATIENT
      POPULATION: 42 consecutive patients OBSERVATION PROCEDURES: Morphological
      evaluation over 24+/-14 months MAIN OUTCOME MEASURES: Remnant pupillary aperture,
      iris colour, visual acuity, intraocular pressure and endothelial cell count.
      RESULTS: In 7 of 42 cases (16.7%), the residual iris aperture dilated from 36.6+/
      15.4 mm2 preoperatively to 61.1+/-12.5 mm2 one year postoperatively (66.9%
      increase). In 5 of 7 affected eyes the artificial iris had been implanted into
      the ciliary sulcus, in 2 eyes it had been sutured to the sclera. 4 of the 7
      patients presented with remarkable complications: 2 eyes needed glaucoma shunt
      surgeries due to pigment dispersion; 1 suffered from recurrent bleedings and in 1
      case artificial iris explantation was performed due to chronic inflammation.
      Anterior chamber depth and angle, endothelial cell count and visual acuity did
      not change in this cohort. Changes in color were not observed in the remnant
      iris. CONCLUSIONS: The implantation of an artificial iris prosthesis can lead to
      a residual iris retraction syndrome. It is likely that residual iris is trapped
      in the fissure between the artificial iris and the anterior chamber angle,
      preventing further pupil constriction. Another possibility could be a
      constriction or atrophy of the residual iris. A scleral-sutured implant or an
      implantation in the capsular bag were both found to prevent the iris retraction.
      The study group number is inadequate to allow statistical comparison of these
      different implantation methods. As the use of artificial irises increases, we may
      expect more patients with iris retraction syndrome in the future.

PMID- 30236773
TI  - Use of the crystalline lens equatorial plane (LEP) as a new parameter for
      predicting postoperative IOL position.
AB  - PURPOSE: To assess whether preoperative crystalline lens equatorial plane (LEP)
      reliably predicts the postoperative position of the intraocular lens (IOL).
      DESIGN: Comparative, interventional case series METHODS: Phacoemulsification and
      IOL implantation (group I; ZCB00, group II; EC-1PAL, and group III; CT Asphina)
      were performed for 104 eyes. Lens geometry parameters, including LEP, were
      obtained from a femtosecond laser cataract surgery system prior to surgery. LEP
      was defined as the distance from the front surface of the cornea to the
      equatorial plane of the crystalline lens. Postoperative anterior chamber depth
      (ACD) was measured using a Scheimpflug camera. Median absolute error was
      calculated using an optical ray tracing method that incorporated LEP into an
      individualized eye model, and the results were compared with those from the
      Haigis formula. RESULTS: Preoperative ACD (3.27+/-0.39 [R=0.428], 3.30+/-0.47
      [R=0.591], and 3.49+/-0.39 mm [R=0.373] in groups I, II, and III, respectively)
      and LEP (4.81+/-0.29 [R=0.570], 4.84+/-0.27 [R=0.634], and 4.97+/-0.23 mm
      [R=0.565] in groups I, II, and III, respectively) were found to have significant
      positive correlations with postoperative ACD (5.24+/-0.40, 5.02+/-0.31, and
      5.19+/-0.26 mm in groups I, II, and III, respectively). Stepwise regression
      analysis showed that postoperative ACD was significantly correlated with LEP in
      all groups. Median absolute errors predicted by the ray tracing method using LEP
      were smaller than those from the Haigis formula in all groups. CONCLUSIONS: LEP
      is a promising measure from preoperative crystalline lens geometry and could
      serve as a new parameter to improve refractive outcomes in cataract surgery.

PMID- 30236772
TI  - Adaptation to Brightness Perception in Patients Implanted with a Small Aperture.
AB  - PURPOSE: Small apertures are successfully used to extend depth of focus in
      presbyopic patients implemented either as corneal inlays or intraocular lenses.
      The use of small apertures reduces retinal illuminance. In this study, we
      quantify the relative perceived brightness in the two eyes of patients implanted
      monocularly with a small aperture inlay. DESIGN: Prospective case series.
      METHODS: We used a binocular adaptive optics vision simulator to determine the
      relative perceived brightness. Four patients implanted monocularly with the KAMRA
      corneal inlay (1.6 mm) and a group of control subjects participated in the study.
      The projected pupil on the eye implanted with the inlay alternated in diameter
      between 0 and 2.5 mm (effective 1.6 mm) to eliminate potential for light to
      project around the periphery of the inlay whilst the corresponding fellow eye
      projected pupil alternated between 0 and 3.0 mm or 0 and 4.0 mm at a frequency of
      1 Hz. Alternation on both eyes was synchronized so that only one eye at a time
      had a non-blocked pupil. At equal transmittance, a flickering was perceived.
      Patients' task consisted of modifying the transmittance of the pupil
      corresponding to the fellow eye until the perceived flickering, due to the
      different perceived brightness, was minimized. This equalizing transmittance (ET)
      value indicates the relative perceived brightness. RESULTS: In the KAMRA's
      patients, it was found it was found a ET greater than expected considering the
      difference in pupil sizes and the Stiles-Crawford effect, showing an enhanced a
      greater brightness perception in the eye with the small aperture in comparison
      with the fellow eye. Compared with the control subjects this difference was on
      average bigger by a factor x1.42. CONCLUSIONS: Patients implanted with the small
      aperture corneal inlay exhibited an enhanced brightness perception with the eye
      implanted in comparison with their untreated fellow eye. The amount of this
      increase is much larger than what could be expected due the Stiles-Crawford
      effect and was probably due to a neural adaptation process. This phenomenon could
      explain a reported equalization of brightness between eyes in patients with
      unilateral inlays and implies that the expected reduction of brightness may have
      a less significant impact on these patients as expected.

PMID- 30236774
TI  - What Is the Amount of Visual Field Loss Associated with Disability in Glaucoma?
AB  - PURPOSE: To propose a new methodology for classifying patient-reported outcomes
      in glaucoma and for quantifying the amount of visual field damage associated with
      disability in the disease. DESIGN: Cross-sectional study. METHODS: 263 patients
      with glaucoma were included. Vision-related disability was assessed by the
      National Eye Institute Visual Function Questionnaire (NEI VFQ-25). A latent class
      analysis (LCA) model was applied to analyze NEI VFQ-25 data and patients were
      divided into mutually exclusive classes according to their responses to the
      questionnaires. Differences in standard automated perimetry (SAP) mean deviation
      (MD) and integrated binocular mean sensitivity (MS) values between classes were
      investigated. The optimal number of classes was defined based on goodness-of-fit
      criteria, interpretability and clinical utility. RESULTS: The model with two
      classes, disabled and non-disabled, had the best fit with an entropy of 0.965,
      indicating excellent separation of classes. The disabled group had 48 (18%)
      patients, whereas 215 (82%) patients were classified as non-disabled. The average
      MD of the better eye in the disabled group was -5.98 dB versus -2.51 dB in the
      non-disabled group (P < 0.001). For the worse eye, corresponding values were 
      13.36 dB and -6.05 dB, respectively (P < 0.001). CONCLUSION: Application of a LCA
      model allowed categorization of patient-reported outcomes and quantification of
      visual field levels associated with disability in glaucoma. A damage of
      approximately -6 dB for SAP MD, indicating relatively early visual field loss,
      may already be associated with significant disability if occurring in the better
      eye.

PMID- 30236775
TI  - Influence Of Age, Sex And Generation On Physician Payments And Clinical Activity
      In Ontario, Canada: An Age-Period-Cohort Analysis.
AB  - PURPOSE: To compare the effect of age, sex and generation on physician practice
      patterns in Ontario, Canada. DESIGN: Retrospective cohort study. METHODS:
      Physician and patient data from 1992-2013 were used to calculate yearly number of
      physicians, distinct patients seen, patient visits, government payments,
      physician age, sex, specialty and year of birth. Age-period-cohort models were
      used for analysis. RESULTS: There was a negligible change in the number of
      distinct patients for all physicians and family physicians and a 20.6% decrease
      for ophthalmologists. There were small declines in yearly visits for all
      physicians (14.2%) and family physicians (17.3%) and a 10.0% increase for
      ophthalmologists. There was a lower number of visits (and patients for
      ophthalmologists) in each succeeding recent birth cohort. For all groups and
      birth cohorts, male physicians had significantly greater number of visits and
      patients. Median payments increased over time in all groups and were less for
      women with an average women-to-men ratio of 0.64 for all physicians, 0.75 for
      family physicians and 0.59 for ophthalmologists. After adjusting for the number
      of visits and patients, sex differences in payments remained significant for all
      physicians and ophthalmologists but were no longer significant for family
      physicians. CONCLUSION: Younger cohorts of Ontario physicians have greater yearly
      payments compared to older cohorts at the same age despite similar or slightly
      less number of visits and patients. The sex gap of payments was mostly explained
      by differences in the number of patients and visits for family physicians however
      remained significant for all physicians and ophthalmologists.

PMID- 30236777
TI  - Electrophysiological signatures of the resting-state fMRI global signal: A
      simultaneous EEG-fMRI study.
AB  - BACKGROUND: The global signal of resting-state functional magnetic resonance
      imaging (fMRI) constitutes an intrinsic fluctuation and presents an opportunity
      to characterize and understand the activity of the whole brain. Recently,
      evidence that the global signal contains neurophysiologic information has been
      growing, but the global signal of electroencephalography (EEG) has never been
      determined. NEW METHODS: We developed a new method to obtain the EEG global
      signal. The EEG global signal was reconstructed by the reference electrode
      standardization technique and represented the outer cortical electrophysiological
      activity. To investigate its relationship with the global signal of resting-state
      fMRI, a simultaneous EEG-fMRI signal was recorded, and this was analyzed in 24
      subjects. RESULTS: We found that the global signal of resting-state fMRI showed a
      positive correlation with power fluctuations of the EEG global signal in the
      gamma band (30-45 Hz) and a negative correlation in the low-frequency band (4-20
      Hz). COMPARISON WITH EXISTING METHOD(S): Compared with the global signal of fMRI,
      the global signal of EEG provides more temporal information about outer cortical
      neural activity. CONCLUSIONS: These results provide new evidence for the
      electrophysiology information of the global signal of resting-state fMRI. More
      importantly, due to its high correlation with the fMRI global signal, the EEG
      global signal may serve as a new biomarker for neurological disorders.

PMID- 30236778
TI  - Hip arthroscopy-MRI correlation and differences for hip anatomy and pathology:
      What radiologists need to know.
AB  - Hip MRI and arthroscopy have important roles for the evaluation of the patient
      with hip pain. An understanding of what orthopedic surgeons want to know before
      and after hip arthroscopy as well as the limitations of arthroscopy would enable
      radiologists to improve their imaging interpretations and produce more clinically
      relevant, management guiding reports. The goal of this article is to review the
      basic principles of hip arthroscopy and MRI and compare their strengths and
      weaknesses. Normal clinically relevant hip anatomy, important pathologic
      conditions such as labral tears and cartilage injuries, femoroacetabular
      impingement specific findings like cam and pincer morphology, extra-articular
      conditions such as abductor and iliopsoas tendons pathology and common post
      operative appearances are reviewed on MRI and arthroscopy.

PMID- 30236779
TI  - Performance and clinical impact of machine learning based lung nodule detection
      using vessel suppression in melanoma patients.
AB  - PURPOSE: To evaluate performance and the clinical impact of a novel machine
      learning based vessel-suppressing computer-aided detection (CAD) software in
      chest computed tomography (CT) of patients with malignant melanoma. MATERIALS AND
      METHODS: We retrospectively included consecutive malignant melanoma patients with
      a chest CT between 01/2015 and 01/2016. Machine learning based CAD software was
      used to reconstruct additional vessel-suppressed axial images. Three radiologists
      independently reviewed a maximum of 15 lung nodules per patient. Vessel
      suppressed reconstructions were reviewed independently and results were compared.
      Follow-up CT examinations and clinical follow-up were used to assess the outcome.
      Impact of additional nodules on clinical management was assessed. RESULTS: In 46
      patients, vessel-suppressed axial images led to the detection of additional
      nodules in 25/46 (54.3%) patients. CT or clinical follow up was available in
      25/25 (100%) patients with additionally detected nodules. 2/25 (8%) of these
      patients developed new pulmonary metastases. None of the additionally detected
      nodules were found to be metastases. None of the lung nodules detected by the
      radiologists was missed by the CAD software. The mean diameter of the 92
      additional nodules was 1.5 +/- 0.8 mm. The additional nodules did not affect
      therapeutic management. However, in 14/46 (30.4%) of patients the additional
      nodules might have had an impact on the radiological follow-up recommendations.
      CONCLUSION: Machine learning based vessel suppression led to the detection of
      significantly more lung nodules in melanoma patients. Radiological follow-up
      recommendations were altered in 30% of the patients. However, all lung nodules
      turned out to be non-malignant on follow-up.

PMID- 30236780
TI  - A new approach to examining the extraction process of Zhishi and Zhiqiao
      considering the synergistic effect of complex mixtures by PAMPA.
AB  - Zhishi (ZS) and Zhiqiao (ZQ) are two important traditional Chinese medicines
      (TCMs) that exert various pharmacological functions due to their active
      ingredients. However, the oral absorption of these ingredients requires further
      study. At the early drug discovery stage, the high-throughput parallel artificial
      membrane permeability assay (PAMPA) is one of the most frequently used to predict
      transcellular passive absorption in in-vitro models. This study aims to establish
      a new approach to examine an optimal extraction process that can take into
      account not only the concentration of active ingredients but also the overall
      absorption properties of the mixtures extracted from TCMs. A high-performance
      liquid chromatography triple-quadrupole mass spectrometry (HPLC-QqQ-MS/MS) method
      was validated for the determination of the effective permeability value (Pe)
      applied to the above experimental medium. The PAMPA experiment showed that
      certain active ingredients such as diosmin, rhoifolin, eriocitrin, narirutin,
      naringin, hesperidin and neohesperidin were not detected in the permeability
      assay of mono-constituents but were well detected and achieved a better
      absorption in the permeability assay of the mixture, indicating that certain
      unknown ingredients may act as cosolvents to improve the solubility or
      permeability of other ingredients. Furthermore, solid phase extraction (SPE) as
      an enrichment and purification process enhances absorption. In the present study,
      a novel in vitro approach was developed to decipher the potential role of TCMs in
      global absorption, and the extraction process for complex TCMs was described and
      systematically optimized.

PMID- 30236781
TI  - Motor dysfunction as research domain across bipolar, obsessive-compulsive and
      neurodevelopmental disorders.
AB  - Although genuine motor abnormalities (GMA) are frequently found in schizophrenia,
      they are also considered as an intrinsic feature of bipolar, obsessive
      compulsive, and neurodevelopmental disorders with early onset such as autism,
      ADHD, and Tourette syndrome. Such transnosological observations strongly suggest
      a common neural pathophysiology. This systematic review highlights the evidence
      on GMA and their neuroanatomical substrates in bipolar, obsessive-compulsive, and
      neurodevelopmental disorders. The data lends support for a common pattern
      contributing to GMA expression in these diseases that seems to be related to
      cerebello-thalamo-cortical, fronto-parietal, and cortico-subcortical motor
      circuit dysfunction. The identified studies provide first evidence for a motor
      network dysfunction as a correlate of early neurodevelopmental deviance prior to
      clinical symptom expression. There are also first hints for a developmental risk
      factor model of these mental disorders. An in-depth analysis of motor networks
      and related patho-(physiological) mechanisms will not only help promoting
      Research Domain Criteria (RDoC) Motor System construct, but also facilitate the
      development of novel psychopharmacological models, as well as the identification
      of neurobiologically plausible target sites for non-invasive brain stimulation.

PMID- 30236776
TI  - Promoting guideline-based cancer genetic risk assessment for hereditary breast
      and ovarian cancer in ethnically and geographically diverse cancer survivors:
      Rationale and design of a 3-arm randomized controlled trial.
AB  - BACKGROUND: Although national guidelines for cancer genetic risk assessment
      (CGRA) for hereditary breast and ovarian cancer (HBOC) have been available for
      over two decades, less than half of high-risk women have accessed these services,
      especially underserved minority and rural populations. Identification of high
      risk individuals is crucial for cancer survivors and their families to benefit
      from biomedical advances in cancer prevention, early detection, and treatment.
      METHODS: This paper describes community-engaged formative research and the
      protocol of the ongoing randomized 3-arm controlled Genetic Risk Assessment for
      Cancer Education and Empowerment (GRACE) trial. Ethnically and geographically
      diverse breast and ovarian cancer survivors at increased risk for hereditary
      cancer predisposition who have not had a CGRA are recruited through the three
      statewide cancer registries. The specific aims are to: 1) compare the
      effectiveness of a targeted intervention (TP) vs. a tailored counseling and
      navigation(TCN) intervention vs. usual care (UC) on CGRA utilization at 6 months
      post-diagnosis (primary outcome); compare the effectiveness of the interventions
      on genetic counseling uptake at 12 months after removal of cost barriers
      (secondary outcome); 2) examine potential underlying theoretical mediating and
      moderating mechanisms; and 3) conduct a cost evaluation to guide dissemination
      strategies. DISCUSSION: The ongoing GRACE trial addresses an important
      translational gap by developing and implementing evidence-based strategies to
      promote guideline-based care and reduce disparities in CGRA utilization among
      ethnically and geographically diverse women. If effective, these interventions
      have the potential to reach a large number of high-risk families and reduce
      disparities through broad dissemination. TRIAL REGISTRATION NUMBER: NCT03326713;
      clinicaltrials.gov.

PMID- 30236783
TI  - An Atomistic Model of a Precursor State of Light-Induced Channel Opening of
      Channelrhodopsin.
AB  - Channelrhodopsins (ChRs) are microbial light-gated ion channels with a retinal
      chromophore and are widely utilized in optogenetics to precisely control neuronal
      activity with light. Despite increasing understanding of their structures and
      photoactivation kinetics, the atomistic mechanism of light gating and ion
      conduction remains elusive. Here, we present an atomic structural model of a
      chimeric ChR in a precursor state of the channel opening determined by an
      accurate hybrid molecular simulation technique and a statistical theory of
      internal water distribution. The photoactivated structure features extensive tilt
      of the chromophore accompanied by redistribution of water molecules in its
      binding pocket, which is absent in previously known photoactivated structures of
      analogous photoreceptors, and widely agrees with structural and spectroscopic
      experimental evidence of ChRs. The atomistic model manifests a photoactivated ion
      conduction pathway that is markedly different from a previously proposed one and
      successfully explains experimentally observed mutagenic effects on key channel
      properties.

PMID- 30236782
TI  - Modeling Structure, Stability, and Flexibility of Double-Stranded RNAs in Salt
      Solutions.
AB  - Double-stranded (ds) RNAs play essential roles in many processes of cell
      metabolism. The knowledge of three-dimensional (3D) structure, stability, and
      flexibility of dsRNAs in salt solutions is important for understanding their
      biological functions. In this work, we further developed our previously proposed
      coarse-grained model to predict 3D structure, stability, and flexibility for
      dsRNAs in monovalent and divalent ion solutions through involving an implicit
      structure-based electrostatic potential. The model can make reliable predictions
      for 3D structures of extensive dsRNAs with/without bulge/internal loops from
      their sequences, and the involvement of the structure-based electrostatic
      potential and corresponding ion condition can improve the predictions for 3D
      structures of dsRNAs in ion solutions. Furthermore, the model can make good
      predictions for thermal stability for extensive dsRNAs over the wide range of
      monovalent/divalent ion concentrations, and our analyses show that the thermally
      unfolding pathway of dsRNA is generally dependent on its length as well as its
      sequence. In addition, the model was employed to examine the salt-dependent
      flexibility of a dsRNA helix, and the calculated salt-dependent persistence
      lengths are in good accordance with experiments.

PMID- 30236784
TI  - Dynamics of Chromatin Fibers: Comparison of Monte Carlo Simulations with Force
      Spectroscopy.
AB  - To elucidate conformational dynamics of chromatin fibers, we compared available
      force-spectroscopy measurements with extensive Monte Carlo simulations of
      nucleosome arrays under external force. Our coarse-grained model of chromatin
      includes phenomenological energy terms for the DNA-histone adhesion and the
      internucleosome stacking interactions. We found that the Monte Carlo fiber
      ensembles simulated with increasing degrees of DNA unwrapping and the stacking
      energy 8 kT can account for the intricate force-extension response observed
      experimentally. Our analysis shows that at low external forces (F < 3.0
      picoNewtons), the DNA ends in nucleosomes breathe by ~10 bp. Importantly, under
      these conditions, the fiber is highly dynamic, exhibiting continuous unstacking
      restacking transitions, allowing accessibility of transcription factors to DNA,
      while maintaining a relatively compact conformation. Of note, changing the
      stacking interaction by a few kT, an in silico way to mimic histone
      modifications, is sufficient to transform an open chromatin state into a compact
      fiber. The fibers are mostly two-start zigzag folds with rare occurrences of
      three- to five-start morphologies. The internucleosome stacking is lost during
      the linear response regime. At the higher forces exceeding 4 picoNewtons, the
      nucleosome unwrapping becomes stochastic and asymmetric, with one DNA arm opened
      by ~55 bp and the other arm only by ~10 bp. Importantly, this asymmetric
      unwrapping occurs for any kind of sequence, including the symmetric ones. Our
      analysis brings new, to our knowledge, insights in dynamics of chromatin
      modulated by histone epigenetic modifications and molecular motors such as RNA
      polymerase.

PMID- 30236785
TI  - Novel Regulatory Elements within Myofilaments of Vertebrate Striated Muscles-Who
      Knew.

PMID- 30236787
TI  - Iron and redox cycling. Do's and don'ts.
AB  - A major form of toxicity arises from the ability of iron to redox cycle, that is,
      to accept an electron from a reducing compound and to pass it on to H2O2 (the
      Fenton reaction). In order to do so, iron must be suitably complexed to avoid
      formation of Fe2O3. The ligands determine the electrode potential; this
      information should be known before experiments are carried out. Only one-electron
      transfer reactions are likely to be significant; thus two-electron potentials
      should not be used to determine whether an iron(III) complex can be reduced or
      oxidized. Ascorbate is the relevant reducing agent in blood serum, which means
      that iron toxicity in this compartment arises from the ascorbate-driven Fenton
      reaction. In the cytosol, an iron(II)-glutathione complex is likely to be the low
      molecular weight iron complex involved in toxicity. When physiologically relevant
      concentrations are used the window of redox opportunity ranges from +0.1 V to
      +0.9 V. The electrode potential for non-transferrin-bound iron in the form of
      iron citrate is close to 0 V and the reduction of iron(III) citrate by ascorbate
      is slow. The clinically utilised chelators desferrioxamine, deferiprone and
      deferasirox in each case render iron complexes with large negative electrode
      potentials, thus being effective in preventing iron redox cycling and the
      associated toxicity resulting from such activity. There is still uncertainty
      about the product of the Fenton reaction, HO* or FeO2+.

PMID- 30236786
TI  - The attenuating effects of 1,2,3,4,6 penta-O-galloyl-beta-d-glucose on pro
      inflammatory responses of LPS/IFNgamma-activated BV-2 microglial cells through
      NFkB and MAPK signaling pathways.
AB  - BACKGROUND: Overactivated microglial cells exhibit chronic inflammatory response
      and can lead to the continuous production of pro-inflammatory cytokines,
      perpetuating inflammation, and ultimately resulting in neuronal injury. 1,2,3,4,6
      Penta-O-Galloyl-beta-d-Glucose (PGG), which is a naturally occurring polyphenolic
      compound, has exhibited anti-inflammatory effect through the inhibition of many
      cytokines in different experimental models, but its effect on activated microglia
      cells was never described. In the present study, we investigated PGG effect in
      proteins involved in the NFkB and MAPK signaling pathways, which play a central
      role in inflammation through their ability to induce transcription of pro
      inflammatory genes. METHODS: PCR arrays and RT-PCR with individual primers were
      used to determine the effect of PGG on mRNA expression of genes involved in NFkB
      and MAPK signaling pathways. Western blots were performed to confirm PCR results.
      RESULTS: The data obtained showed that PGG modulated the expression of 5 genes
      from the NFkB (BIRC3, CHUK, IRAK1, NFkB1, NOD1) and 2 genes from MAPK signaling
      pathway (CDK2 and MYC) when tested in RT-PCR assays. Western blots confirmed the
      PCR results at the protein level, showing that PGG attenuated the expression of
      total and phosphorylated proteins (CDK2, CHUK, IRAK1, and NFkB1) involved in NFkB
      and MAPK signaling. CONCLUSION: These findings show that PGG could modulate the
      expression of genes and proteins involved in the production of pro-inflammatory
      cytokines in microglia cells.

PMID- 30236789
TI  - Redox and NF-kappaB signaling in osteoarthritis.
AB  - Human cells have to deal with the constant production of reactive oxygen species
      (ROS). Although ROS overproduction might be harmful to cell biology, there are
      plenty of data showing that moderate levels of ROS control gene expression by
      maintaining redox signaling. Osteoarthritis (OA) is the most common joint
      disorder with a multi-factorial etiology including overproduction of ROS. ROS
      overproduction in OA modifies intracellular signaling, chondrocyte life cycle,
      metabolism of cartilage matrix and contributes to synovial inflammation and
      dysfunction of the subchondral bone. In arthritic tissues, the NF-kappaB
      signaling pathway can be activated by pro-inflammatory cytokines, mechanical
      stress, and extracellular matrix degradation products. This activation results in
      regulation of expression of many cytokines, inflammatory mediators, transcription
      factors, and several matrix-degrading enzymes. Overall, NF-kappaB signaling
      affects cartilage matrix remodeling, chondrocyte apoptosis, synovial
      inflammation, and has indirect stimulatory effects on downstream regulators of
      terminal chondrocyte differentiation. Interaction between redox signaling and NF
      kappaB transcription factors seems to play a distinctive role in OA pathogenesis.

PMID- 30236788
TI  - Cmk2 kinase is essential for survival in arsenite by modulating translation
      together with RACK1 orthologue Cpc2 in Schizosaccharomyces pombe.
AB  - Different studies have demonstrated multiple effects of arsenite on human
      physiology. However, there are many open questions concerning the mechanism of
      response to arsenite. Schizosaccharomyces pombe activates the Sty1 MAPK pathway
      as a common response to several stress conditions. The specificity of the
      response is due to the activation of different transcription factors and specific
      targets such the Cmk2 MAPKAP kinase. We have previously shown that Cmk2 is
      phosphorylated and activated by the MAPK Sty1 in response to oxidative stress.
      Here, we report that Cmk2 kinase is specifically necessary to overcome the stress
      caused by metalloid agents, in particular arsenite. Deletion of cmk2 increases
      the protein level of various components of the MAPK pathway. Moreover, Cmk2
      negatively regulates translation through the Cpc2 kinase: the RACK1 orthologue in
      fission yeast. RACK1 is a receptor for activated C-kinase. Interestingly, RACK1
      is a constituent of the eukaryotic ribosome specifically localized in the head
      region of the 40 S subunit. Cmk2 controls arsenite response through Cpc2 and it
      does so through Cpc2 ribosomal function, as observed in genetic analysis using a
      Cpc2 mutant unable to bind to ribosome. These findings suggest a role for Cmk2 in
      regulating translation and facilitating adaptation to arsenite stress in the
      ribosome.

PMID- 30236790
TI  - Physicians' Attitudes Toward Euthanasia and Assisted Suicide in Italy.

PMID- 30236791
TI  - PC-FACS.
AB  - PC-FACS (FastArticleCriticalSummaries for Clinicians inPalliativeCare) provides
      hospice and palliative care clinicians with concise summaries of the most
      important findings from more than 100 medical and scientific journals. If you
      have colleagues who would benefit from receiving PCFACS, please encourage them to
      join the AAHPM at aahpm.org. Comments from readers are welcomed at pc
      facs@aahpm.org.

PMID- 30236793
TI  - Analysis of a survey on orthopaedic residency training for fracture treatment in
      Korea.
AB  - INTRODUCTION: Fracture surgery is the most frequently performed orthopaedic
      procedure and is considered an essential surgical procedure for orthopaedic
      surgeons in general. Although the approach and circumstances of orthopaedic
      residency training for fracture treatment may differ between countries, the goals
      of training, which is to educate the residents regarding the principles of the
      fracture treatment and foster conscientious orthopaedic specialists, remain
      unchanged. Thus, the aim of the this study was to determine a desirable course of
      orthopaedic residency training by investigating and analysing the reality of
      training associated with fracture surgery and treatment during the orthopaedic
      residency of 4th year orthopaedic residents in Korea. METHODS: Using a
      questionnaire survey, a one-on-one interview was proposed to 266 applicants
      following the secondary board examination of residents who had completed the
      orthopaedic residency training course; the survey was conducted on January 19,
      2016. Responses from 152 applicants (response rate: 57%) who accepted to
      participate in the survey were statistically analysed. RESULTS: During residency
      training, clinicians underwent fracture-related training for 3.5 h on average per
      month. Training consisted of various approaches and included lectures by
      professors, case briefings, textbook reading, and field training in an operating
      room. The residents largely differed in terms of experience in conducting
      fracture surgery: 47 (31%) responded that they had never performed fracture
      surgery during the training period, whereas 21 (14%) answered that they had
      conducted fracture surgery over 20 times. Experience in performing the surgical
      procedure was the most valuable in fracture training. CONCLUSION: To optimize
      fracture education among orthopaedic residents, the professors at teaching
      hospitals should understand the realities of fracture education, dedicate
      sufficient time for internal and external fracture teachings, and allow residents
      to perform fracture surgeries hands-on under their supervision, and also attempt
      to foster a social atmosphere that encourages all three factors.

PMID- 30236792
TI  - Maternal Lipids and Fetal Overgrowth: Making Fat from Fat.
AB  - There is increasing recognition that maternal glucose concentrations lower than
      those previously used for diagnosis of gestational diabetes mellitus (GDM) and
      targeted for treatment can result in excess fetal growth. Yet, mothers with GDM
      who appear to have optimal glycemic control and mothers with obesity and normal
      glucose tolerance still have a significantly increased risk for delivering
      infants who are large for gestational age, or even more importantly, who have
      increased adiposity at birth. What is less appreciated is that in addition to
      glucose, maternal lipids are also substrates for fetal fat accretion and that
      placental lipases can hydrolyze maternal triglycerides (TGs) to free fatty acids
      for fetal-placental availability. Maternal TG levels are 40% to 50% higher on
      average in mothers with obesity and GDM compared to those in normal-weight
      mothers early in pregnancy and are sustained at higher levels throughout
      gestation. Increasing evidence supports that maternal TG, both fasting and
      postprandial, are also predictors of newborn adiposity (newborn %fat), a risk
      factor for childhood obesity, and that early exposure is at least as strong of a
      risk factor as later exposure in mothers with obesity. In the setting of maternal
      nutrient excess and maternal insulin resistance, which lead to fetal
      hyperinsulinemia, excess free fatty acid exposure in the fetus may result in
      lipid storage and fetal fat development in subcutaneous and possibly other
      depots. In this commentary, we provide further evidence to make a case for
      targeting maternal fasting and postprandial TG in mothers with obesity who have
      elevated TG in early pregnancy to determine whether a TG-lowering interventional
      approach might limit fetal overgrowth and potentially mitigate the intrauterine
      contribution to childhood obesity and metabolic disease.

PMID- 30236794
TI  - Reprocessing safety issues associated with complex-design orthopaedic loaned
      surgical instruments and implants.
AB  - BACKGROUND: The acquisition of reusable surgical instruments (RSIs) through
      loaner system is a worldwide phenomenon, particularly in orthopaedic surgeries.
      Loaner sets contain high-complex design RSIs, which are very difficult to clean,
      and also include single use implants, such as screws, that remain in the surgical
      tray and are subjected to multiple reprocessing until they are implanted.
      Inadequate cleaning of SI and various exposures of single-use implants to
      physical, chemical and biological agents can compromise their quality/safety and
      promote biofilm formation. The difficulty in cleaning is compounded in middle and
      low-income countries where automated cleaning infrastructure at sterilizing
      service units is often unavailable, and thus manual cleaning only is performed.
      Thus, we aimed to determine the condition of orthopaedic loaned sets when
      delivered to the hospital, assess the quality of complex-design RSIs reprocessed
      by manual cleaning, and evaluate the effect of multiple reprocessing on single
      use implant (screw). METHODS: Flexible medullary reamers (FMRs), depth gauges and
      screws used for femur intramedullary nailing, in clinical use for >1 year, were
      obtained from three Brazilian loaner companies and assessed for residual ATP,
      protein, bacterial contamination, endotoxin and/or biofilm at delivery at the
      hospital, following cleaning and steam sterilisation. RESULTS: Before cleaning,
      blood was visible on a RSIs tray, and RSIs/screws were contaminated with high
      amounts of ATP, protein and bacteria. Visible soil was released during brushing
      of a FMR lumen and, following cleaning, the inner layer of 34/40 were visible
      soiled, and over 5/8 were protein test positive. Following sterilisation, biofilm
      and soil, including fragments appearing to be bone, were detected by scanning
      electron microscopy on RSIs/screws. A sterilised FMR revealed visible soil on the
      inner layer. Endotoxin tests were negative. CONCLUSION: The contaminated
      condition of loaned-complex-designed RSIs/screws upon arrival at the hospital and
      after reprocessing points to the insufficiency of manual reprocessing and
      management practices related to this instruments/implants. A multidisciplinary
      approach involving expert in design/manufacture, regulating, managing,
      reprocessing and surgeons is suggested to improve RSIs manufacture that enables
      complete decontamination and maintain the surgical patient safety.

PMID- 30236795
TI  - Trauma assessment and follow up with integration of modern communication devices
      (TRAFIC). A pilot study.
AB  - OBJECTIVES: This pilot study aimed to evaluate the feasibility of prospectively
      collecting electronic PROMs on patients being assessed as a result of
      musculoskeletal trauma, using a web-based application (APP), administered onto
      tablet and desktop computers (TCs or DCs) in the outpatient setting. METHODS:
      Following local research ethics approval, a web-based APP (TRAFIC) was developed.
      It consisted of a total of 12 questions (demographic information, employment, and
      rehabilitation status as well as quality of life (EQ5D)). The APP was viewable on
      TCs, with DCs being used in review cubicles when necessary with assistance from a
      medical professional. Eligible patients were invited to use TRAFIC during the
      'Lag period'; the time period from the patient 'booking in' to 'being called' for
      their appointment. An evaluation of the total time spent using the app (APP
      time), was recorded as well as the total time spent in the outpatient department
      (CLINIC-time) for all patients recruited. CLINIC-time was also assessed for a
      control group of patients not utilising the APP during their outpatient
      assessment. RESULTS: One hundred patients were recruited for the study n = 50
      males, n = 50 females with a mean age of 49.1 (+/- 17.6 years). All recruited
      patients completed the questionnaire items with a median APP-time of 5 min (range
      2-118 min). The median 'Lag period' was 16 min. (Range 2-166 min), with a median
      CLINIC-time of 81 min (range 4-428). The CLINIC-time was higher than for the
      control group (median 67 min (range 18-242) but this was not statistically
      significant (Mann Whitney U test; p = 0.199). CONCLUSIONS: Electronic PROMs
      collection in the musculoskeletal trauma outpatient clinic using a web-based APP
      is feasible, with the APP-time falling well within the 'Lag period', and no
      significant impact on the total time spent for the appointment.

PMID- 30236797
TI  - Functional outcomes of traumatic midfoot injuries.
AB  - INTRODUCTION: Midfoot injuries are rare injuries, often the result of high-energy
      trauma and occurring in the context of multiple trauma. This study aimed to
      evaluate functional outcomes and health-related quality of life after open
      reduction and internal fixation for midfoot injuries at a level 1 trauma center
      treating complex foot injuries. METHODS: Retrospective single level 1 center
      study with follow-up by questionnaire. All adult patients who underwent open
      reduction and internal fixation (ORIF) for Lisfranc and/or Chopart injuries
      between 2000 and 2016 were included and invited to complete the American
      Orthopaedic Foot and Ankle Society (AOFAS) Midfoot Score, the EuroQOL Visual
      Analog Scale (EQ-VAS), and the EuroQOL five-dimensional questionnaire (EQ-5D-5L).
      Chart reviews were performed to collect demographic, injury, and treatment
      characteristics. RESULTS: Forty patients with 45 midfoot injuries were included.
      Follow-up was available for 29 patients (31 feet), leading to a response rate of
      83%. The majority of patients suffered high-energy trauma and nearly all patients
      had a concomitant injury. Secondary arthrodesis was performed in 7/45 injuries.
      Median AOFAS score was 64 (IQR 47-78). Higher injury severity score (ISS) was
      associated with poorer functionality as measured with the AOFAS Midfoot Score (p
      =  0.046), concomitant injuries were associated with lower quality of life (p =
      0.01). EQ-5D scores were significantly lower when compared to the Dutch reference
      population (p< 0.001). CONCLUSIONS: Injuries of the midfoot have negative effects
      on mid- to long-term quality of life after trauma, with considerable potential
      for long-term impaired functionality. When counseling patients with these rare
      injuries after high-energy trauma mechanisms or in the context of multiple
      trauma, realistic expectations on postoperative recovery should be given.

PMID- 30236796
TI  - Metabolic syndrome and hip fracture: Epidemiology and perioperative outcomes.
AB  - INTRODUCTION: Hip fractures and metabolic syndrome (MetS) are becoming major
      global healthcare burdens as populations age. This study sought to determine the
      impact of MetS in hip fracture patients on perioperative outcomes following
      operative fixation or arthroplasty. METHODS: Data from the 2004-2014 Nationwide
      Inpatient Sample was used to select 3,348,207 discharges with hip fracture. MetS
      patients were identified by having at least 3 of 4 component comorbidities:
      hypertension, dyslipidemia, obesity, and diabetes. Logistic regression was used
      to estimate odds ratios for the association between MetS and perioperative
      outcomes adjusted for age, gender, race, payer status, and comorbidities.
      RESULTS: Overall, 32% of hip fracture patients were treated with open reduction
      internal fixation (ORIF), 28% hemiarthroplasty (HA), 18% closed reduction with
      internal fixation (CRPP), and 3% primary total hip arthroplasty (THA). The
      remaining 19% of cases were either treated via unspecified procedure of hip
      repair (9%), managed non-operatively (2%), underwent multiple procedures during
      the hospital stay (6%), or the surgical procedure data was missing (2%) and were
      excluded from procedural analyses. The prevalence of MetS was 7.9% and increased
      among minorities, patients treated at urban hospitals, with comorbidities (heart
      failure, kidney disease, peripheral vascular disease), and with Medicare
      coverage. MetS was associated with increased odds of any adverse event (p <
      0.0001), specifically: acute renal failure, myocardial infarction, acute
      posthemorrhagic anemia. MetS was also associated with increased LOS (p < 0.0001)
      and increased total charges (p < 0.0001). However, MetS was associated with
      reduced odds of postoperative pneumonia, deep vein thrombosis and pulmonary
      embolism, surgical site infection, septicemia, and in-hospital mortality (p <
      0.0001). The above associations were maintained for MetS patients stratified
      according to their treatment groups: HA, CRPP, and ORIF. CONCLUSIONS: MetS is
      associated with increased odds of complications in hip fracture patients but
      decreased odds of in-hospital mortality. This may be related to patients'
      nutritional status and catabolic states in the perioperative period.

PMID- 30236798
TI  - Letter to the Editor regarding: "A novel approach to improving the interpretation
      of CT brain in trauma".

PMID- 30236799
TI  - Alternating block copolymer-based nanoparticles as tools to modulate the loading
      of multiple chemotherapeutics and imaging probes.
AB  - Cancer therapy often relies on the combined action of different molecules to
      overcome drug resistance and enhance patient outcome. Combined strategies relying
      on molecules with different pharmacokinetics often fail due to the lack of
      concomitant tumor accumulation and, thus, to the loss of synergistic effect. Due
      to their ability to enhance treatment efficiency, improve drug pharmacokinetics,
      and reduce adverse effects, polymer nanoparticles (PNPs) have been widely
      investigated as co-delivery vehicles for cancer therapies. However, co
      encapsulation of different drugs and probes in PNPs requires a flexible polymer
      platform and a tailored particle design, in which both the bulk and surface
      properties of the carriers are carefully controlled. In this work, we propose a
      core-shell PNP design based on a polyurethane (PUR) core and a phospholipid
      external surface. The modulation of the hydrophilic/hydrophobic balance of the
      PUR core enhanced the encapsulation of two chemotherapeutics with dramatically
      different water solubility (Doxorubicin hydrochloride, DOXO and Docetaxel, DCTXL)
      and of Iron Oxide Nanoparticles for MRI imaging. The outer shell remained
      unchanged among the platforms, resulting in un-modified cellular uptake and in
      vivo biodistribution. We demonstrate that the choice of PUR core allowed a high
      entrapment efficiency of all drugs, superior or comparable to previously reported
      results, and that higher core hydrophilicity enhances the loading efficiency of
      the hydrophilic DOXO and the MRI contrast effect. Moreover, we show that changing
      the PUR core did not alter the surface properties of the carriers, since all
      particles showed a similar behavior in terms of cell internalization and in vivo
      biodistribution. We also show that PUR PNPs have high passive tumor accumulation
      and that they can efficient co-deliver the two drugs to the tumor, reaching an 11
      fold higher DOXO/DCTXL ratio in tumor as compared to free drugs. STATEMENT OF
      SIGNIFICANCE: Exploiting the synergistic action of multiple chemotherapeutics is
      a promising strategy to improve the outcome of cancer patients, as different
      agents can simultaneously engage different features of tumor cells and/or their
      microenvironment. Unfortunately, the choice is limited to drugs with similar
      pharmacokinetics that can concomitantly accumulate in tumors. To expand the
      spectrum of agents that can be delivered in combination, we propose a multi
      compartmental core-shell nanoparticles approach, in which the core is made of
      biomaterials with high affinity for drugs of different physical properties. We
      successfully co-encapsulated Doxorubicin Hydrochloride, Docetaxel, and contrast
      agents and achieved a significantly higher concomitant accumulation in tumor
      versus free drugs, demonstrating that nanoparticles can improve synergistic
      cancer chemotherapy.

PMID- 30236800
TI  - Advances in synthesis of biotin and assembly of lipoic acid.
AB  - Although biotin and lipoic acid are two universally conserved cofactors essential
      for intermediary metabolism, their synthetic pathways have become known only in
      recent years. Both pathways have unusual features. Biotin synthesis in
      Escherichia coli requires a methylation that is later removed whereas lipoic acid
      is assembled on the enzymes where it is required for activity by two different
      pathways.

PMID- 30236801
TI  - A comparison of the interviewer-administered phone and self-complete online
      versions of the computerized eMINI 6.0 in a sample of pregnant women.
AB  - BACKGROUND: This study compares the prevalence rates of depressive and anxiety
      disorders identified during pregnancy using an interviewer-administered phone
      version and a self-complete online version of the computerized eMINI 6.0.
      METHODS: 888 pregnant women completed the computerized eMINI 6.0 (interviewer
      administered phone, n = 253; self-complete online, n = 635). RESULTS: There were
      no significant differences in the proportions of women meeting eMINI 6.0 criteria
      for current major depression, any current anxiety disorder, or lifetime panic or
      depressive disorder, by mode of administration. However, a greater proportion of
      women in the interviewer-administered phone group than in the self-complete
      online group met criteria for current minor depression (2.0% vs 0.2%, p = .008).
      LIMITATIONS: Study limitations include its non-randomized design, overall low
      prevalence of depressive and anxiety disorders in the sample and inclusion of
      only a select number of eMINI 6.0 modules. CONCLUSIONS: This study demonstrated
      few differences in the rates of DSM-IV depressive and anxiety disorders
      identified between the interviewer-administered and self-administered versions of
      the eMINI 6.0. Findings provide preliminary support the practical value of self
      completed computerized interviews in large scale studies examining common mental
      disorders in pregnant women.

PMID- 30236802
TI  - Hypokalemic thyrotoxic periodic paralysis. Report of one case.

PMID- 30236803
TI  - Multiplex recognition and logic devices for molecular robot prototype based on an
      europium(iii)-cyclen system.
AB  - Molecular robot provides a promising way to receive response signals and make
      decisions with intelligent information processing at the molecule level. In this
      work, a molecular robot prototype based on a europium(III)-cyclen complex (EuL)
      was designed and assembled, consisting of multiplex sensing and information
      processing in a single system. By utilizing the Eu3+ ion as a central processing
      unit (CPU) and terpyridine (Terpy) group as an arm of the molecular robot,
      multiplex detection function of this molecular robot can be accomplished in three
      test channels: the detection of Fe2+ with UV-vis, Zn2+ using photoluminescence,
      and Mn2+ using magnetic resonance imaging. The optimized structures revealed that
      the transition metal ions bound by the arms of two EuL molecules formed a
      hexacoordination octahedral rigidity structure in the adducts. For the structure
      of L and EuL, three pyridine rings of Terpy unit were not in a plane, and they
      were fixed to form a plane when captured the transition metal ions during the
      formation of the adducts. In addition, three different modes of molecular logic
      devices (OR, INHIBIT, and YES) were established based on relevant signals in the
      multiplex detection channels. The sensing of metal ions in human urine using EuL
      was also carried out, and the result demonstrated the presence of good recoveries
      and high analytical precision. Such a molecular robot prototype is expected to be
      used in intelligent medical diagnostics and, in particular, information
      processing at molecular level.

PMID- 30236804
TI  - Single-step detection of norovirus tuning localized surface plasmon resonance
      induced optical signal between gold nanoparticles and quantum dots.
AB  - A new method of label free sensing approach with superior selectivity and
      sensitivity towards virlabel-freeon is presented here, employing the localized
      surface plasmon resonance (LSPR) behavior of gold nanoparticles (AuNPs) and
      fluorescent CdSeTeS quantum dots (QDs). Inorganic quaternary alloyed CdSeTeS QDs
      were capped with L-cysteine via a ligand exchange reaction. Alternatively,
      citrate stabilized AuNPs were functionalized with 11-mercaptoundecanoic acid to
      generate carboxylic group on the gold surface. The carboxylic group on the AuNPs
      was subjected to bind covalently with the amine group of L-cysteine capped
      CdSeTeS QDs to form CdSeTeS QDs/AuNPs nanocomposites. The fluorescence of CdSeTeS
      QDs/AuNPs nanocomposite shows quenched spectrum of CdSeTeS QDs at 640 nm due to
      the close interaction with AuNPs. However, after successive addition of norovirus
      like particles (NoV-LPs), steric hindrance-induced LSPR signal from the adjacent
      AuNPs triggered the fluorescence enhancement of QDs in proportion to the
      concentration of the target NoV-LPs. A linear range of 10-14 to 10-9 g mL-1 NoV
      LPs with a detection limit of 12.1 * 10-15 g mL-1 was obtained. This method was
      further applied on clinically isolated norovirus detection, in the range of 102
      105 copies mL-1 with a detection limit of 95.0 copies mL-1, which is 100-fold
      higher than commercial ELISA kit. The superiority of the proposed sensor over
      other conventional sensors is found in its ultrasensitive detectability at low
      virus concentration even in clinically isolated samples. This proposed detection
      method can pave an avenue for the development of high performance and robust
      sensing probes for detection of virus in biomedical applications.

PMID- 30236805
TI  - A novel aptasensor based on 3D-reduced graphene oxide modified gold nanoparticles
      for determination of arsenite.
AB  - In this study, a sensitive aptasensor based on three-dimensional reduced graphene
      oxide-modified gold nanoparticles (3D-rGO/AuNPs) was fabricated for the
      determination of arsenite (As(III)). The 3D-rGO/AuNPs was fully characterized
      with various techniques. The 5'-thiolate aptamer was first self-assembled on a
      glassy carbon electrode (GCE) that it's modified with 3D-rGO/AuNPs via Au-S
      covalent bonding. In the presence of As(III), the G-quadruplex interaction was
      formed between a single-stranded DNA and the target, which produced a hindrance
      for electron transfer. Consequently, the electrochemical impedance spectroscopy
      signals of a GCE modified with 3D-rGO/AuNPs was increased. In order to improve
      the response of the designing aptasensor, the effect of the various parameters
      was optimized. Under the optimal conditions, the aptasensor has an
      extraordinarily low detection limit of 1.4 * 10-7 ng mL-1 toward As(III) with a
      dynamic range of 3.8 * 10-7 3.0 * 10-4 ng mL-1. The 3D-rGO/AuNPs aptasensor
      displayed superior selectivity and reproducibility with an acceptable recovery
      for determination of As(III) in real water samples.

PMID- 30236806
TI  - Ultrasensitive and portable assay of mercury (II) ions via gas pressure as
      readout.
AB  - It is of the significant importance to achieve facile and on-site detection of
      heavy metal ions due to the serious harm to environment and human health. Herein,
      a facile and portable strategy was developed for detection of Hg2+ via portable
      pressure meter. Biotinylated DNA1 was conjugated on the surface of streptavidin
      coated magnetic beads (MBs) to form MBs-DNA1 complex. In the presence of Hg2+,
      MBs-DNA1 can hybridize with platinum nanoparticles (PtNPs)-functionalized DNA2
      (DNA2-PtNPs) via T-Hg2+-T binding. Then, PtNPs effectively catalyzed the
      decomposition of H2O2 to generate oxygen, leading to an increase in pressure of
      sealed well of 96-well plate. The gas pressure was linearly related with the
      concentration of Hg2+ in the range between 10 pM and 100 nM with a detection
      limit of 2.79 pM, which is more sensitive than most of the previous reports. The
      specific T-Hg2+-T binding made it easy to selectively detect Hg2+ even when other
      metal ions co-existed with Hg2+. Therefore, it offers a cost-effective, rapid,
      facile and portable way to detect Hg2+ by combining gas-generation reaction with
      T-Hg2+-T binding, which holds great potential for detecting Hg2+ in water sample.

PMID- 30236807
TI  - A photoelectrochemical sensor for highly sensitive detection of amyloid beta
      based on sensitization of Mn:CdSe to Bi2WO6/CdS.
AB  - A high sensitivity photoelectrochemical (PEC) immunosensor for amyloid beta
      (Abeta) detection, which has great neurotoxic effect on the progression of
      Alzheimer's disease (AD), was presented based on the sensitization of Mn2+ doped
      CdSe (Mn:CdSe) to Bi2WO6/CdS electrode. Bi2WO6 was synthesized successfully with
      a unique flower-like amorphous structure, providing a merit to load functional
      CdS for obtaining an expected PEC response. Mn:CdSe was used to label Abeta for
      acquiring Mn:CdSe-Abeta bioconjugate and enhancing the detection sensitivity via
      the competitive immunoreaction of Mn:CdSe-Abeta and Abeta with antibody
      immobilized on Bi2WO6/CdS electrode. The doped of Mn2+ in CdSe nanoparticles
      could induce energy defect that impeded the recombination of photo-generated
      charges, and greatly enhanced PEC response for ultrasensitive detection of Abeta.
      The proposed immunosensor for Abeta showed a linear range of 0.2 pg mL-1-50 ng mL
      1 with a detection limit of 0.068 pg mL-1, also with good stability, high
      selectivity, and acceptable reproducibility. The sensitization of Mn:CdSe
      provided a new way for preparation of highly sensitive protein biosensors.

PMID- 30236808
TI  - A highly sensitive and reliable detection of CA15-3 in patient plasma with
      electrochemical biosensor labeled with magnetic beads.
AB  - An early on-time detection of breast cancer can effectively affect the outcome of
      the treatment. Here, we developed an ultrasensitive, simple and reliable
      immunosensor to detect the lowest alteration of CA 15-3, the standard biomarker
      of breast cancer patients. The proposed immunosensor was achieved by modification
      of gold electrode by streptavidin to immobilize the biotinylated anti-CA 15-3
      monoclonal antibody (mAb). Bovine serum albumin was used to prevent nonspecific
      binding. To improve the sensitivity of modified immunosensor, the sandwich signal
      enhancer consisting of streptavidin-coated magnetic beads conjugated with
      biotinylated horseradish peroxidase (HRP) and anti-CA 15-3 biotinylated mAb was
      applied. The electrochemical measurements were obtained in the presence of
      hydroquinone as a redox agent and H2O2 as the activating agent of HRP. Under
      optimized condition and using square wave voltammetry, the lower limit of
      quantification was obtained as 15 * 10-6 U/mL and the linear CA 15-3
      concentration range was 50-15 * 10-6 U/mL. While showing significant stability,
      the immunosensor displayed an excellent sensitivity and specificity for the
      detection of CA 15-3 even in the human serum as compared to the enzyme-linked
      immunosorbent assay (ELISA) as a gold standard method. Based on our findings, the
      engineered immunosensor is proposed as a robust diagnostic tool for the clinical
      determination of CA 15-3 and other cancer biomarkers.

PMID- 30236809
TI  - Transclival Venous Circulation: Anatomic Study.
AB  - INTRODUCTION: The clivus is a small, central area of the basal cranium with
      limited surgical access and high morbidity associated with pathologies of its
      surrounding structures. Therefore thorough knowledge and understanding of the
      anatomy in this region are crucial for the success of treatments and
      interpretation of imaging. As to our knowledge, there is no extant cadaveric
      examination of the transclival veins, so the present study was performed.
      METHODS: Fifteen lightly embalmed adult heads underwent blue latex injection of
      the left and right internal jugular veins. Special attention was given to the
      presence or absence of transclival vessels. When transclival veins were
      identified, their intracranial source, point of penetration of the clivus and
      anterior connections were documented. RESULTS: Ten (66.7%) specimens were found
      to have transclival veins. These connected the basilar venous plexus to the
      retropharyngeal venous plexus on all specimens. Eight of the 10 specimens had
      multiple transclival veins, and 2 had only 1 vessel. The majority of the
      transclival veins were found penetrating the clivus at its lower one third.
      However, 2 specimens also had transclival veins that pierced the clivus at its
      upper one third. CONCLUSIONS: An improved understanding of the skull base and its
      venous drainage can assist clinicians and surgeons in better understanding
      normal, pathologic, and variant anatomy in this region.

PMID- 30236810
TI  - Initial Results of Bilateral Subthalamic Nucleus Stimulation for Parkinson
      Disease in a Newly Established Center in a Developing Country: Shiraz, Southern
      Iran.
AB  - OBJECTIVE: To report the establishment of a new center for deep brain stimulation
      (DBS) as a surgical treatment for Parkinson disease and the surgical outcomes,
      from 2014 to 2017 in Shiraz, Southern Iran. METHODS: A new treatment program was
      established in Shiraz through a multidisciplinary team in 2014. Thirty-four
      patients underwent implantation of subthalamic nucleus (STN) electrodes during
      the last 3 years. Twenty-five patients fulfilled the minimum 6-month follow-up
      criteria. The baseline Unified Parkinson Disease Rating Scale (UPDRS) was
      assessed 1 month before surgery in both off-medication and on-medication states
      by a movement disorder neurologist. To evaluate the outcomes, subscores of the
      UPDRS were assessed in all patients before surgery and at least 6 months after
      the operation. RESULTS: All 25 patients had advanced Parkinson disease
      categorized as stage 3 or 4 using the Hoehn and Yahr scale. STN DBS resulted in a
      dramatic improvement in motor function of most patients. A reduction in
      dopaminergic medication dosage (average 60% reduction) was observed. The mean
      improvement was 40% in UPDRS II and 67% in UPDRS III. No surgical or hardware
      complications were observed. Stimulation-related adverse effects, including
      increased falling and worsening of speech, occurred in a few patients after
      surgery. Most of the patients experienced weight gain after surgery. CONCLUSIONS:
      Bilateral STN DBS is a satisfactory and safe treatment for carefully selected
      patients with advanced Parkinson disease. According to the results, the procedure
      can be performed safely and with comparable results in developing countries
      around the world.

PMID- 30236811
TI  - Intracranial Arterial Tortuosity According to the Characteristics of Intracranial
      Aneurysms.
AB  - OBJECTIVE: Intracranial aneurysm (IA) is the leading cause of subarachnoid
      hemorrhage. The pathomechanisms of IA are poorly understood but can be related to
      arterial tortuosity resulting from underlying systemic factors leading to
      arterial wall weakening. We aimed to analyze the tortuosity of the intracranial
      artery in a cohort with IA, hypothesizing that the tortuosity of intracranial
      arteries differs depending on the characteristics of the IA. METHODS: Patients
      with saccular IA were consecutively enrolled. Clinical factors and vascular
      tortuosity of the right and left middle cerebral arteries and basilar artery (BA)
      of all patients with IA were compared according to the characteristics of the IA:
      1) ruptured versus unruptured, 2) multiple versus single, and 3) large (>5 cm)
      versus small (<=5 cm). Unruptured IAs were comparatively analyzed according to
      aneurysm size and aspect ratio, whereas ruptured IAs were analyzed according to
      aneurysm size. RESULTS: Two hundred eighty-five patients were enrolled (mean age,
      59 years; 71.2% women). The tortuosity of the BA was higher in the large IA group
      (5.63 +/- 6.26; n = 133; P = 0.009), large unruptured IA group (6.64 +/- 6.32; n
      = 53; P = 0.039), and large ruptured IA group (5.50 +/- 6.52; n = 80; P = 0.033)
      compared with the small IA, small unruptured IA, and small ruptured IA group. In
      multivariate analysis, increased BA tortuosity was significantly associated with
      large IAs (beta = 1.066; P = 0.008), unruptured large IAs (beta = 1.077; P =
      0.033), and ruptured large IAs (beta = 1.086; P = 0.025). CONCLUSIONS: The BA
      tortuosity was higher in patients with large IAs, which may represent an imaging
      biomarker of aneurysm growth.

PMID- 30236812
TI  - Factors Associated with Cervical Spine Alignment in an Asymptomatic Population: A
      Preliminary Analysis.
AB  - BACKGROUND: Cervical sagittal imbalance compromises health-related quality of
      life and can lead to myriad incapacitating symptoms through compression of the
      spinal cord. Questions regarding which parameters play primary roles in the
      progression of cervical sagittal imbalance and which might be compensatory
      factors remain unanswered. METHODS: This study enrolled 246 asymptomatic
      volunteers from July 2016 to June 2018. After demographic and radiologic
      parameters were measured, the data were analyzed using correlation coefficient
      test and multiple regression analysis. A predictive equation was assessed with
      variance analysis, residual analysis, collinearity analysis, and a paired t test.
      RESULTS: Average values are as follows: orbital tilt, 64 +/- 6 degrees ; orbital
      slope (OS), 15 +/- 6 degrees ; C0-C2 lordosis (C0C2), 28 +/- 8 degrees ; cervical
      lordosis (CL), 5 +/- 11 degrees ; C2-C7 sagittal vertical axis (C2C7SVA), 15 +/-
      8 mm; T1 slope (TS), 17 +/- 6 degrees ; thoracic inlet angle, 69 +/- 8 degrees ;
      thoracic kyphosis, 34 +/- 9 degrees ; lumbar lordosis, 50 +/- 10 degrees ; sacral
      slope, 38 +/- 7 degrees ; pelvic index, 48 +/- 9 degrees ; sagittal vertical
      axis, 10 +/- 19 mm. Correlations of C2C7SVA were observed with body mass index
      (BMI), OS, C0C2, CL, and TS. The validated predictive equation was: C2C7SVA =
      0.38 * BMI - 0.73 * OS + 0.73 * C0C2 + 0.15 * CL + 0.18 * TS - 6.53. CONCLUSIONS:
      BMI, OS, C0C2, CL, and TS were primary influencers in the progression of cervical
      sagittal imbalance and established a predictive equation of asymptomatic
      population, which can provide clinical advice and remind surgeons of the primary
      influencers of reconstructive surgery for better prognoses.

PMID- 30236813
TI  - Susceptibility-Weighted Imaging of Deep Venous Congestion in Petroclival
      Meningioma.
AB  - BACKGROUND: Protecting the venous drainage route during surgery in cases of
      petroclival meningioma (PCM) is important. Identifying venous congestion
      preoperatively can be valuable in reducing the risks associated with venous
      congestion during surgery. In this study, we examined the utility of
      susceptibility-weighted imaging (SWI) in identifying the presence of venous
      congestion in PCM cases preoperatively and identified the factors associated with
      it. METHODS: We retrospectively examined 24 patients who had undergone surgery
      for primary PCM. The areas of the basal and internal cerebral veins on the
      affected and unaffected sides, obtained using SWI, were compared to identify
      venous congestion. We further examined the association between multiple candidate
      factors that are thought to be related to venous congestion and venous congestion
      using statistical analyses. RESULTS: SWI could successfully identify venous
      congestion in 11 of 24 PCM cases. Among the 12 factors examined, those associated
      with venous congestion were an extension of the tumor, over the midline or
      upward, which is known to disturb the venous flow at the brainstem surface;
      anastomosis of the superficial cerebral vein (i.e., bypass route for venous
      congestion); and a high ABC Surgical Risk Scale score, an indicator of
      postoperative neurologic deterioration. CONCLUSIONS: We showed that SWI is useful
      for evaluating venous congestion in PCM cases preoperatively and for identifying
      factors reflecting the risk of venous congestion. Taken together, our findings
      provide a multimodal strategy for the preoperative prediction of venous
      congestion, which could facilitate the treatment of PCM.

PMID- 30236814
TI  - Proton Magnetic Resonance Spectroscopy (H1-MRS) Study of the Ketogenic Diet on
      Repetitive Mild Traumatic Brain Injury in Adolescent Rats and Its Effect on
      Neurodegeneration.
AB  - OBJECTIVE: A ketogenic diet (KD) improves cellular metabolism and functional
      recovery after moderate-to-severe traumatic brain injury. Here, we evaluated the
      changes of neurochemical metabolites after KD therapy for repetitive mild
      traumatic brain injury (rmTBI) and its possible role in neurodegeneration.
      METHODS: Postnatal day 35 rats were randomly divided into 3 groups: sham,
      control, and KD groups. Rats in control and KD groups were given 3 rmTBI by a
      fluid percussion traumatic brain injury device 24 hours apart. All rats were
      killed at 7 days after the last injury. The ipsilateral cortex were analyzed with
      hematoxylin and eosin staining; beta-hydroxybutyrate was measured; conventional
      magnetic resonance imaging and the dry-wet weight method were used to assess the
      brain edema; changes of neurochemical metabolites were assessed using the ratio
      of N-acetylaspartate (NAA)/creatine (Cr), choline compound (Cho)/Cr, and NAA/Cho
      with magnetic resonance spectroscopy; the effect of KD therapy on
      neurodegeneration was evaluated with double immunofluorescence staining of Iba
      1/beclin-1; behavioral outcome was assessed with beam walk/beam balance tests.
      RESULTS: KD significantly elevated beta-hydroxybutyrate levels, and there was no
      brain edema associated with rmTBI and KD therapy; behavioral assessment showed KD
      therapy significantly improved motor performance; magnetic resonance spectroscopy
      showed that rmTBI reduced the ratio of NAA/Cr and had no effect on the ratios of
      Cho/Cr and NAA/Cho whereas KD increased the ratio of NAA/Cr; double
      immunofluorescence staining showed KD therapy could significantly decrease
      microglial beclin-1 expression in the ipsilateral cortex. CONCLUSIONS: These
      results suggest the effect of KD on metabolic status and its possible role in
      preventing neurodegeneration in adolescent rats after rmTBI.

PMID- 30236815
TI  - Increasing ambulatory treatment of pediatric minor burns-The emerging paradigm
      for burn care in children.
AB  - INTRODUCTION: Innovations in topical burn treatment along with a drive toward
      value-based care are steering burn care to the outpatient setting. Little is
      known regarding what characteristics predict outpatient treatment of pediatric
      minor burns and whether there is a temporal trend toward this treatment paradigm.
      METHODS: A retrospective cohort study was performed using California's Office of
      Statewide Health Planning and Development linked emergency department and
      inpatient database (2005-2013). All patients under 18years of age with a primary
      burn diagnosis were extracted. Using patient and facility level variables, we
      used regression modeling to evaluate predictors of outpatient burn treatment and
      temporal trends. RESULTS: There were 16,480 pediatric minor burn encounters
      during the period. 56.4% were male, 85.3% had <10% total body surface area
      (TBSA), 76.3% were scald or contact, and 77.3% were at deepest depth 2nd degree.
      Multiple variables predicted an increased likelihood of discharge home including
      older age(p<0.001), smaller TBSA(p<0.001), and superficial/partial thickness
      burns(< 0.001). Children of Hispanic and Black race were less likely to be
      discharged home compared to White and Asian peers(p=<0.001). On Poisson modeling,
      the incidence rate ratio over the 9-year period for home discharge was 1.004 (95%
      CI 1.001-1.008, p=0.032). CONCLUSION: Older patients and those with more
      superficial burns were more likely to be treated as outpatients. Black and non
      white Hispanic race was associated with inpatient admission. There is a growing
      trend toward ambulatory treatment of minor burns in the pediatric population.
      Further research is needed to assess whether outpatient treatment of pediatric
      minor burns results in greater readmissions.

PMID- 30236816
TI  - Using the injury severity score to adjust for comorbid trauma may be double
      counting burns: implications for burn research.
AB  - BACKGROUND: The injury severity score considers burn size and inhalation injury
      in estimating overall anatomical injury severity. Models that adjust for injury
      severity score in addition to total burn size and inhalation injury may therefore
      be double counting the risk from these individual burn characteristics, and
      obscuring (or overemphasizing) the contribution of risk from each source. The
      primary aim of this study was to compare differences in the estimated mortality
      risk of burn trauma using the traditional injury severity score (ISS) calculation
      and the non-burn injury severity score (NBISS) to examine how separating out the
      risk attributable to the burn injury versus other trauma changes the
      interpretation and clinical assessment. METHODS: Among U.S. casualties sustaining
      burns during combat operations in Iraq and Afghanistan from March 2003 to October
      2013, we performed a retrospective cohort study. Unadjusted, adjusted, and
      weighted Cox proportional hazards models were performed to estimate the risk of
      age, burn injury severity, and non-burn injury severity on mortality. Weighted
      hazard ratios and adjusted survival curves were performed using non-parametric
      inverse probability weighting. RESULTS: Our final sample consisted of 902 service
      members with a mortality proportion of 5.7% (n=51). Adjusting for non-burn trauma
      with traditional ISS attenuated the risk of percent total body surface area
      burned (%TBSA) by 20% when modeled continuously [HR (95% CI): 1.27 (1.10-1.32)
      vs. 1.07 (0.99-1.15]. However, the adjusted model using NBISS only attenuated the
      associated mortality risk of burn size by 5% [HR (95% CI): 1.22 (1.12-1.34)] and
      had a similar model fit (AIC: 484.2 vs. 478.6). For the weighted Cox proportional
      hazards models, the risk from a large burn (%TBSA>=60) was also attenuated when
      adjusting for ISS [HR (95% CI): 2.80 (1.18-6.64)] compared to the model adjusting
      for NBISS [HR (95% CI): 5.63 (2.79-11.35)]. CONCLUSION: Our analysis comparing
      the use of traditional ISS and NBISS to measure comorbid non-burn trauma resulted
      in different interpretations for the effect of %TBSA on subsequent mortality. Our
      results suggest that the association of %TBSA with death can be obscured by the
      inclusion of traditional ISS. Therefore, we recommend using NBISS when
      constructing statistical models in this patient population.

PMID- 30236817
TI  - Re-evaluation of websites from burn centers in Austria, Germany and Switzerland.
AB  - INTRODUCTION: Websites serve as information and communication platforms; hence,
      they are important tools for the self-promotion of hospitals. In 2010, Selig et
      al. evaluated the online presence of burn centers in Germany, Austria, and
      Switzerland based on 37 quality criteria. This study aimed to re-evaluate these
      websites to assess their development over the past 6.5 years. MATERIALS AND
      METHODS: Websites of the German-speaking burn centers were re-evaluated according
      to criteria previously described by Selig et al. Particular attention was paid to
      specific information on burns. Additionally, the implementation of social media
      platforms was investigated. RESULTS: There was an overall increase in the quality
      of information published on websites. There was a considerable improvement
      recorded, especially in the categories of "teaching" and "patient care." However,
      burn-specific information was found to be still sparse. Over 50% of the hospitals
      were present on social media. CONCLUSIONS: Although the quality of information
      published on German-speaking burn center websites increased, they must be further
      developed, especially regarding burn-related information. Moreover, a clear
      structure and design could prevent long searches and facilitate an easier flow of
      information. The interface from websites and social media platforms appear to be
      an important tool for up-to-date self-promotion.

PMID- 30236818
TI  - Identification and structure elucidation of a new degradation impurity in the
      multi-component tablets of amlodipine besylate.
AB  - New unknown impurity at m/z 421.15 was observed during the accelerated stability
      analysis (40  degrees C/75% relative humidity) in the multi-component tablets of
      amlodipine besylate by reversed-phase ultra-high performance liquid
      chromatography-mass spectrometry (UHPLC-MS). UHPLC-MS and nuclear magnetic
      resonance (NMR) techniques were employed to identify and fully characterize the
      degradation compound. The degradation product was unambiguously identified as 3
      ethyl 5-methyl 4-(2-chlorophenyl)-6-methyl-2-(morpholin-2-yl)-1,4-dihydropyridine
      3,5-dicarboxylate and mechanism of its formation was proposed. It was confirmed
      that the degradation product was formed by the reaction of amlodipine with
      formaldehyde originating from the excipients present in the dosage form.

PMID- 30236819
TI  - Optimization of an innovative vinylimidazole-based monolithic stationary phase
      and its use for pressured capillary electrochromatography.
AB  - A novel polymer monolith based on the dicationic crosslinker 3,3'-(hexane-1,6
      diyl)bis(1-vinylimidazolium) bromide, the monomer 1-vinylimidazole and a ternary
      porogen mixture (1-propanol, decan-1-ol and water) was developed and optimized
      for capillary electrochromatography. This aim was accomplished by adjusting the
      composition of individual constituents in the polymerization mixture and
      monitored based on several relevant parameters (e.g. pore structure by scanning
      electron microscopy, generation of electroosmotic flow, or permeability of
      material). The ultimately selected composition yielded a monolithic phase which
      excellently resolved six methylxanthines (including caffeine, theobromine and
      theophylline) in 15 min. Key requirements concerning the utilized buffer were an
      acidic pH of 3 and the addition of 50% acetonitrile; additionally, a negative
      voltage (-25 kV) had to be applied during analyses. The proposed separation
      mechanism was mixed mode, i.e. the combination of electrostatic repulsion and
      hydrophobic interaction. Monolith fabrication as well as separation efficiency
      were found to be highly repeatable, the material was mechanically stable and
      useable for at least 150 injections. Thus the presented stationary phase is
      definitely a very promising option for CEC.

PMID- 30236820
TI  - Candidate reference measurement procedure for determination of urea in serum by
      liquid chromatography-tandem mass spectrometry.
AB  - Urea is an important indicator of liver and kidney disease, and very frequently
      determined in clinical chemistry. The reference measurement procedures (RMPs) for
      serum urea recognized by the Joint Committee for Traceability in Laboratory
      Medicine are spectrophotometry, and isotope dilution (ID)-mass spectrometry (MS)
      coupled with gas chromatography. This study investigated a candidate RMP (cRMP)
      for detecting serum urea directly via ID-liquid chromatography (LC)-MS/MS,
      without derivatization, which simplifies pre-processing samples. The cRMP was
      developed and evaluated relative to the recognized RMP, inter- and intra
      laboratories. The intra-precisions were 1.35%, 1.98% and 1.47% at 4.95, 24.74 and
      31.36 mmol/L, respectively; inter-precision was 2.10%, 2.60% and 2.10%. The
      relative bias for the measurement of standard human serum (SRM 909c) was -0.49%.
      The relative biases were 0.41% and 0.02% for IFCC-RELA (International Federation
      of Clinical Chemistry and Laboratory Medicine-External Quality Assessment Scheme
      [EQAS] for reference laboratories) 2015A and 2015B. The linearity response
      between 2.4 mmol/L and 53.7 mmol/L was R2 = 0.9989. No carryover, ion
      suppression, or interference was detected. Correlation was acceptable with the
      reference spectrophotometry (R2 = 0.9985, P <  0.0001). Between our laboratory
      and other reference laboratories, the absolute deviation range for IFCC-RELA
      2016A and 2016B was from -0.63 to 1.52 mmol/L. This well-characterized cRMP for
      urea can provide a base of accuracy for the traceability of clinical systems.

PMID- 30236822
TI  - [Renal amyloidosis revealing a cryopyrin associated periodic syndrome].
AB  - INTRODUCTION: Cryopyrin associated periodic syndrome is a rare auto inflammatory
      disease including three clinical entities with a common genetic cause. Among
      these three entities, Muckle-Wells syndrome is described as an intermediate
      phenotype associated with a progressive sensorineural hearing loss and AA
      amyloidosis. The present case reports a renal AA amyloidosis associated with an
      IgA nephropathy, revealing a Muckle-Wells syndrome. OBSERVATION: The case is
      reported of a 38-years-old patient who presented a renal failure revealed
      concomitantly with a macroscopic hematuria exploration. Urological investigations
      were performed with negative results. The patient had no particular background
      except urticarial rashes, unlabeled inflammatory rheumatism and a grandmother's
      amyloidosis. Renal biopsy revealed glomerular, vascular and interstitial AA
      amyloidosis associated to an IgA nephropathy. This amyloidosis was known to be a
      part of Muckle-Wells syndrome, and a NLRP3 gene study confirmed the diagnosis.
      CONCLUSION: Cryopyrin associated periodic syndrome is a rare disease and the
      clinical diagnosis suspicion need genetic confirmation. AA amyloidosis is known
      to happen in Muckle-Wells syndrome. Other occasional renal impairments are
      described in this syndrome whereas the IgA nephropathy association remains poorly
      characterized.

PMID- 30236821
TI  - Pharmacokinetics and tissue distribution of N-(2-hydroxyphenyl)-2
      propylpentanamide in Wistar Rats and its binding properties to human serum
      albumin.
AB  - N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) is a novel valproic acid
      derivative that has shown anti-proliferative activity against epitheloid cervix
      carcinoma (HeLa), rhabdomyosarcoma (A204), and several breast cancer cell lines.
      The aim of this research was to evaluate the pharmacokinetic profile and tissue
      distribution of HO-AAVPA in Wistar rats, as well as its human serum albumin
      binding potential by experimental and in silico methods. A single dose of HO
      AAVPA was given to male rats by intravenous, intragastric or intraperitoneal
      routes at doses of 25, 100, and 100 mg/kg, respectively. Then, blood samples were
      drawn at predetermined intervals of time, and the HO-AAVPA concentration in the
      plasma was quantified with a validated HPLC method. The elimination half-life
      (t1/2) was approximately 222 min, and the systemic clearance (CL) and apparent
      volume of distribution (Vd) were 2.20 mL/min/kg and 0.70 L/kg, respectively. The
      absolute oral bioavailability of HO-AAVPA was 33.8%, and the binding rate of HO
      AAVPA with rat plasma proteins was between 66.2% and 83.0%. Additionally, in
      silico, UV and Raman spectroscopy data showed weak interactions between the test
      compound and human serum albumin. Thus, the results that were obtained
      demonstrated that despite its low oral bioavailability, the potential anticancer
      agent HO-AAVPA exhibits acceptable pharmacokinetic properties that would allow it
      to reach its site of action and exert its pharmacological effect in Wistar Rats,
      and it has a convenient profile for future assays to evaluate its human
      applications.

PMID- 30236823
TI  - [Dermatopathology histoseminar. Interstitial granuloma annulare, case 8].

PMID- 30236824
TI  - Human mitochondrial DNA haplogroup M8a influences the penetrance of m.8684C>T in
      Han Chinese men with non-obstructive azoospermia.
AB  - RESEARCH QUESTION: What is the role of mitochondrial DNA (mtDNA) in the
      pathogenesis of non-obstructive azoospermia (NOA)? DESIGN: mtDNA genome
      sequencing followed by an independent population validation were performed in 628
      NOA cases and 584 healthy controls. Antioxidant capacity of serum was evaluated
      in 54 randomly selected cases out of 536 and 49 out of 489 controls. RESULTS: In
      the screening stage, 13 mtDNA haplogroups (hg) were ascertained, and 10
      susceptible variants were observed. In the validation stage, hg M8* in
      individuals was found to be associated with increased risk of NOA [odds ratio
      (OR) 2.61, 95% confidence interval (CI) 1.47-4.61] (P=0.001). Unexpectedly, the
      frequency of m.8684C>T, the defining marker for hg M8a, was also higher in NOA
      (OR 4.14, 95% CI 1.56-11.03) (P=0.002). Subsequently, the frequency distributions
      were compared among the sub-hg of hg M8* (including hg M8a, C and Z) and,
      intriguingly, no significance was found in hg C and Z. Additionally, the level of
      total antioxidant capacity was significantly decreased (P<0.05) compared with the
      control group. CONCLUSIONS: hg M8a background in general played an active role in
      the penetrance of 8684C>T in NOA, and mtDNA genetic variants (causing low
      antioxidant levels) might increase mtDNA damage and impair normal
      spermatogenesis.

PMID- 30236826
TI  - Depressive symptoms may increase the risk of the future development of freezing
      of gait in patients with Parkinson's disease: Findings from a 5-year prospective
      study.
AB  - INTRODUCTION: Prospective studies identifying predictors of freezing of gait
      (FOG) in Parkinson's disease (PD) are limited. We aim to explore which symptoms
      are associated with future development of FOG in non-freezers. METHODS: Fifty
      seven PD patients without FOG at baseline were re-evaluated after a mean of five
      years. At baseline, disease severity [Unified Parkinson's Disease Rating Scale
      (MDS-UPDRS)], gait under single and dual-tasking, balance, cognition and other
      non-motor symptoms were assessed. The new-FOG-questionnaire (NFOG-Q) determined
      FOG. Multivariate binary logistic regression determined independent predictors of
      FOG. RESULTS: At follow-up, 26 subjects (46%) had FOG while 31 remained non
      freezers. At baseline, non-freezers (FOG-) and future freezers (FOG+) were
      similar (p > 0.10) with respect to age, gender, disease duration, dopaminergic
      medications, and cognitive function. However, FOG + had significantly worse
      scores on the Geriatric Depression Scale (GDS) (FOG+:5.2 +/- 3.7; FOG-:2.4 +/-
      2.0, p = 0.005), PDQ-39, the NMS-questionnaire, UPDRS-part I, UPDRS-part III
      (off), and the Berg Balance Scale. In binary logistic regression, GDS, gait speed
      and UPDRS-III (on vs. off) were the only significant independent predictors of
      future FOG (GDS: OR = 10.93, p = 0.003, DeltaUPDRS-III: OR = 1.34, p = 0.006).
      Moreover, 80% of the subjects who had marked depressive symptoms at baseline
      (GDS>=5) developed FOG at follow-up. In contrast, only 27% of those with few
      depressive symptoms at baseline became freezers (p < 0.001). CONCLUSIONS:
      Depressive symptoms apparently precede the development of FOG. While elucidation
      of the relationship between depression and FOG needs further study, our findings
      offer another perspective regarding the pathophysiology of FOG and may help
      clinicians to estimate the risk of developing this debilitating phenomenon.

PMID- 30236825
TI  - Intraoperative sentinel node imaging versus SPECT/CT in oral cancer - A blinded
      comparison.
AB  - INTRODUCTION: Sentinel node biopsy (SNB) is gaining popularity as a staging tool
      in oral cancer. Protocol mandates radiotracer injection and pre-operative imaging
      (LSG +/- SPECT/CT) in the nuclear medicine department. This approach limits
      application to accessible tumours and to centres with nuclear medicine. New
      technology, freehand single photon emission computed tomography (fhSPECT), has
      proved a useful adjunct in intraoperative imaging and localisation of sentinel
      nodes. This study investigates fhSPECT as an alternative to traditional imaging,
      an approach that would widen the remit of SNB. METHODS: Fifty consecutive cT1-T2
      N0 oral cancer patients received radiotracer followed by lymphoscintigraphy and
      SPECT/CT. Surgery was undertaken using fhSPECT by a surgeon blinded to pre
      operative imaging. Prior to biopsy completion, results of pre-operative imaging
      were reviewed and any additional nodes removed. The accuracy of LSG, SPECT/CT and
      fhSPECT were compared. RESULTS: Nineteen patients had positive sentinel nodes.
      Disease free survival for sentinel node positive versus negative was significant
      (p < 0.005). All modalities missed positive nodes in at least one patient. The
      false negative rate for lymphoscintigraphy, SPECT/CT and fhSPECT was 26.3%, 15.8%
      and 5.3% respectively. DISCUSSION: These data show a surgeon naive to the results
      of traditional pre-operative sentinel node imaging can use fhSPECT in the
      operating theatre to accurately locate sentinel nodes in oral cancer. Freehand
      SPECT showed excellent sensitivity and a low false negative rate offering the
      possibility of a streamlined intraoperative sentinel node protocol.

PMID- 30236827
TI  - Expert comment to "Simultaneous acute presentation of generalized chorea and
      subacute combined degeneration of the spinal cord secondary to vitamin B12
      deficiency".

PMID- 30236828
TI  - Diagnosis of PSP-P: Can a newly developed MRPI make the difference?

PMID- 30236829
TI  - Sociocultural dynamics that influence Chagas disease health care in Colombia.
AB  - Chagas disease (CD) is a Latin America endemic and neglected tropical disease
      that affects primarily poor people living in rural areas. Its current low profile
      leads to many diagnostic, treatment, and control challenges. This study aimed to
      identify and characterize the sociocultural dynamics that influence CD health
      care in Colombia. Data for our ethnographic study was collected in 2013 and
      included participant observation in two main endemic areas in Colombia. In
      addition, 81 people belonging to four groups (patients and family members; health
      care workers; researchers; and officers) were recruited through snowball sampling
      technique and participated in informal and semi-structured interviews. People
      from the first two groups also participated in social cartography excercises.
      Data analysis resulted in the identification of three main sociocultural
      dynamics. Local Understandings: Patients reported confusions around disease
      transmission, treatment effectiveness and development of future complications.
      Providers' Knowledge and Training: Failures in professional's knowledge and
      training mostly affect the primary level of care in rural areas. Professionals
      undergo minimal training during medical school and lack access to continuous
      education. In contrast, clinicians working at tertiary university hospitals or at
      the CD unit of the Colombian National Institute of Health (NIH) exhibited great
      knowledge and competency. Health Care System Barriers: The Colombian market-based
      health care reform augmented access barriers, which impacted CD care greatly. We
      identified geographic and bureaucratic itineraries that depended on type of
      insurance plan, insurance contracts with service providing institutions, and
      levels of care. This study shows that people's experience of these sociocultural
      dynamics vary depending on their mobility from rural to urban contexts. It
      unveils the importance of analyzing the structure of the health care system. In
      the Colombian case, its for-profit orientation has become one of the most
      important obstacles for comprehensive, integrated, and timely health care
      responses.

PMID- 30236830
TI  - Multicenter assessment of a hemoglobin A1c point-of-care device for diagnosis of
      diabetes mellitus.
AB  - OBJECTIVE: A multisite investigation compared the analytical performance of a
      point-of-care (POC) HbA1c device with multiple commonly used HbA1c laboratory
      methods and an NGSP (National Glycohemoglobin Standardization Program) reference
      method. RESEARCH DESIGN AND METHODS: The Afinion AS100 POC device analyzed HbA1c
      using 618 EDTA whole blood excess patient specimens with clinically indicated
      HbA1c testing. Results were compared to measurements across five clinical
      laboratories and the NGSP reference method. Precision was evaluated over 8-10
      consecutive days for low-, mid-, and high-range HbA1c specimens at all five
      sites. RESULTS: Over a wide range of HbA1c values (4.0%-15% HbA1c), 97.1% of the
      POC results and 94.5% of routine laboratory results fell within the target value
      of +/-6% of the NGSP reference method results. The POC HbA1c results at 6.5%
      exhibited a total relative bias of -0.6% (-0.04% HbA1c) compared to the reference
      method while the aggregate of laboratory methods displayed a relative bias of 
      0.9% (-0.06% HbA1c). The total imprecision of the POC results ranged from 0.74
      2.13% CV across the analytic measurement range compared to 0.81-3.23% CV for the
      routine laboratory methods. CONCLUSIONS: The accuracy and precision of the
      Afinion POC HbA1c method was comparable to the laboratory HbA1c methods
      supporting the FDA's recent approval of the Afinion HbA1c Dx device for use in
      the diagnosis of diabetes.

PMID- 30236831
TI  - Autophagy-related 16-like 1gene polymorphism, risk factors for cardiovascular
      disease and associated carotid intima-media thickness in postmenopausal women.
AB  - BACKGROUND: Early identification of asymptomatic postmenopausal women (PW), who
      are more predisposed to developing cardiovascular disease (CVD), is an important
      preventive strategy. Autophagy-related 16-like 1 (ATG16L1) is an autophagy gene
      known to control host immune responses and is associated with a variety of
      diseases, including CVD. OBJECTIVE: The aim of the study was to associate the
      ATG16L1 polymorphism variant with subclinical carotid atherosclerosis in
      asymptomatic PW. STUDY DESIGN: This cross-sectional study included 210 Brazilian
      postmenopausal women (age >= 45 years with amenorrhea >=12 months). Clinical,
      anthropometric and biochemical assessments were performed to evaluate the
      cardiovascular risk factors. DNA was extracted from buccal cells and the ATG16L1
      (T300A) polymorphism was determined by the polymerase chain reaction (PCR). The
      carotid intima-media thickness and/or the presence of plaques were evaluated by
      carotid duplex ultrasound. For statistical analysis, the t-test, logistic
      regression and analysis of covariance (ANCOVA) were used. RESULTS: The presence
      of the polymorphic allele forATG16L1 (T300A) was found in 77.47% (A/G = 49.87%,
      G/G = 27.60%). The ATG16L1 (T300A) polymorphism is significantly associated with
      increased carotid intima-media thickness (IMT) after adjustments of the
      confounding variables (P < .037). No significant associations were observed
      between the polymorphism with other risk factors for CVD in PW. CONCLUSION: In
      postmenopausal women, the ATG16L1 (T300A) polymorphism is significantly
      associated with increased carotid IMT (marker of atherosclerotic disease) after
      adjustments of the confounding variables (P < .037). Thus, identifying the
      ATG16L1 polymorphism is an important strategy for screening asymptomatic PW who
      are more predisposed to developing CVD.

PMID- 30236832
TI  - Immunohistochemical analysis of the development of olfactory organs in two
      species of turtles Pelodiscus sinensis and Mauremys reevesii.
AB  - The nasal cavity of turtles is composed of the upper and lower chambers, lined by
      the upper and lower chamber epithelia, respectively. In many turtles including
      the Reeve's turtle Mauremys reevesii, the upper chamber epithelium contains
      ciliated olfactory receptor neurons (ORNs) and the lower chamber epithelium
      contains microvillous ORNs. However, in the olfactory organ of the Chinese soft
      shelled turtle Pelodiscus sinensis, both the upper and lower chamber epithelia
      contain ciliated ORNs. In the present study, we immunohistochemically examined
      the developmental process of olfactory organs in soft-shelled turtle and the
      Reeve's turtle to clarify the developmental origins of the lower chamber
      epithelium in these turtles. Obtained data indicate that olfactory organs of
      these turtles have identical origin and follow similar process of development,
      suggesting that, in the lower chamber epithelium of the nasal cavity, ciliated
      ORNs differentiate in soft-shelled turtle whereas microvillous ORNs differentiate
      in the Reeve's turtle.

PMID- 30236833
TI  - hsa_circ_0061140 Knockdown Reverses FOXM1-Mediated Cell Growth and Metastasis in
      Ovarian Cancer through miR-370 Sponge Activity.
AB  - Circular RNAs (circRNAs) are a class of noncoding RNAs that regulate gene
      expression at the posttranscriptional level. The specific functions of circRNAs
      in ovarian cancer are yet to be established. Previous sequencing analyses have
      revealed an abnormal expression of hsa_circ_0061140 in ovarian cancer. The main
      aim of the present study is to establish the specific role of hsa_circ_0061140 in
      ovarian cancer. circRNA expression in ovarian cancer cells was detected via real
      time qPCR. The effects on specific cellular characteristics (proliferation,
      migration, and the EMT) and subcellular localization of hsa_circ_0061140 were
      assessed via RNA fluorescence in situ hybridization, knockdown, and luciferase
      reporter assays in the SKOV3 and A2780 cell lines. Tumorigenesis was induced in
      nude mice to assess the effects of hsa_circ_0061140 on ovarian cancer growth in
      vivo. Our results showed that hsa_circ_0061140 was upregulated in ovarian cancer
      cell lines. Knockdown of hsa_circ_0061140 suppressed cell proliferation and
      migration, both in vivo and in vitro, by inhibiting FOXM1 expression through
      sponging miR-370. Overexpression of FOXM1 or suppression of miR-370 rescued
      hsa_circ_0061140 silencing-induced inhibition of cell proliferation, migration,
      and the EMT. The associations among hsa_circ_0061140, miR-370, and FOXM1 were
      confirmed via bioinformatic prediction and fluorescein reporter experiments.
      Thus, hsa_circ_0061140 appeared to function as a competing endogenous RNA of miR
      370 that promoted cell growth and metastasis in ovarian cancer through regulation
      of the miR-370/FOXM1 pathway mediating EMT.

PMID- 30236834
TI  - Development of pre and post-operative models to predict early recurrence of
      hepatocellular carcinoma after surgical resection.
AB  - BACKGROUND & AIMS: Resection is the most widely used potentially curative
      treatment for patients with early hepatocellular carcinoma (HCC). However,
      recurrence within 2 years occurs in 30-50% of patients, being the major cause of
      mortality. Herein, we describe 2 models, both based on widely available clinical
      data, which permit risk of early recurrence to be assessed before and after
      resection. METHODS: A total of 3,903 patients undergoing surgical resection with
      curative intent were recruited from 6 different centres. We built 2 models for
      early recurrence, 1 using preoperative and 1 using pre and post-operative data,
      which were internally validated in the Hong Kong cohort. The models were then
      externally validated in European, Chinese and US cohorts. We developed 2 online
      calculators to permit easy clinical application. RESULTS: Multivariable analysis
      identified male gender, large tumour size, multinodular tumour, high albumin
      bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters
      related to early recurrence. Using these variables, a preoperative model (ERASL
      pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort -
      low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2
      year RFS 20.7%. Median survival in each stratum was similar between centres and
      the discrimination between the 3 strata was enhanced in the post-operative model
      (ERASL-post) which included 'microvascular invasion'. CONCLUSIONS: Statistical
      models that can predict the risk of early HCC recurrence after resection have
      been developed, extensively validated and shown to be applicable in the
      international setting. Such models will be valuable in guiding surveillance
      follow-up and in the design of post-resection adjuvant therapy trials. LAY
      SUMMARY: The most effective treatment of hepatocellular carcinoma is surgical
      removal of the tumour but there is often recurrence. In this large international
      study, we develop a statistical method that allows clinicians to estimate the
      risk of recurrence in an individual patient. This facility enhances communication
      with the patient about the likely success of the treatment and will help in
      designing clinical trials that aim to find drugs that decrease the risk of
      recurrence.

PMID- 30236835
TI  - Do MOOCs encourage corporate social responsibility or are they simply a marketing
      opportunity?
AB  - This paper explores institutional drivers for developing MOOCs by juxtaposing
      them against the original drivers for generating MOOCs: to offer open access
      education. However, the original impetus for MOOC development may be shifting
      towards a business oriented model. Therefore, instead of contributing to
      corporate social responsibility and inclusivity agendas facilitating open access
      to education, MOOCs are akin to an institution's shop window allowing the pseudo
      'purchaser' the opportunity to glimpse behind the scenes. Hence, we ask: are
      MOOCs merely a sophisticated form of window dressing, showing pseudo 'purchasers'
      what institutions want them to see enticing them to purchase more lucrative
      products? Notwithstanding the motivation for developing MOOCs participants must
      first access them. Therefore the paper examines what MOOCs actually offer
      participants who are likely to access them and concludes by examining how MOOCs
      can be developed to facilitate better completion rates and encourage wider
      participation from hard to access groups.

PMID- 30236836
TI  - Challenging oppressive practice in mental health: The development and evaluation
      of a video based resource for student nurses.
AB  - Some aspects of mental health nursing practice are inherently oppressive; for
      example detention in hospital or forced medication under restraint. What is more
      challenging is thinking about oppression in the context of everyday mental health
      nursing work, such as nursing handovers, and the impact this has on the quality
      and safety of service user care. An online resource was co-developed for use (via
      a workshop) with student mental health nurses to assist them with questioning
      their own and others practice in relation to oppression as exhibited in the
      nursing handover. The resource was evaluated using an approach broadly informed
      by Kirkpatrick and Kirkpatrick's four levels of learning model. Qualitative
      interviews were conducted with 12 student mental health nurses immediately at the
      end of the session where they were introduced to the video resource and again
      when they returned to school following their final management placement (24
      interviews in total). Data was analysed using thematic analysis. Three
      overarching themes were identified: "enabling reflection on and in real life";
      "surfacing mundane practice" and "confidence to challenge". Video based resources
      act as "tools" to facilitate reflective practice and enable student nurses to
      engage critically in questioning their own and others practice.

PMID- 30236837
TI  - Indications, risks and impact of failed allograft nephrectomy.
AB  - In this review, we describe the indications, surgical aspects, benefits and risks
      of nephrectomy after graft failure. There is a great variation in the number of
      allograft nephrectomies performed among different centers. Nephrectomy of a
      failed allograft is associated with significant morbidity and mortality with a
      complication rate of 20-30% and mortality rates between 0% and 11%. A systematic
      review through Medline (Pubmed) and Embase identified thirteen retrospective
      studies that compared patients with and patients without allograft nephrectomy
      prior to retransplantation. Allograft nephrectomy associates with an increased
      risk of HLA antibody development. With two recent studies that used the more
      sensitive HLA antibody detection methods disproving the hypothesis of intragraft
      adsorption of HLA antibodies, the mechanism leading to the increased HLA antibody
      levels is not clear, but the role of immunosuppression withdrawal is becoming
      clear and needs further investigation. In nine of the thirteen studies that
      evaluated the impact of allograft nephrectomy on outcome in retransplantation,
      retransplant graft survival was not significantly different among patients with
      and patients without allograft nephrectomy. Only three studies showed
      significantly worse retransplant graft survival if prior allograft nephrectomy
      was performed. Most studies did not observe a significant difference in patient
      survival after retransplantation with versus without prior allograft nephrectomy.
      All studies were affected by the retrospective design, indication bias, and
      selection bias. On the basis of the available literature on this topic, we did
      not identify a clear advantage or disadvantage of allograft nephrectomy, in terms
      of outcome after repeat transplantation. Nevertheless, the significantly
      increased risk of HLA antibody sensitization, especially in patients at high
      immunological risk like high donor-recipientHLA epitope mismatch load and HLA
      DQB1 mismatches, argues against routine allograft nephrectomy and
      immunosuppression withdrawal in asymptomatic patients who are eligible for repeat
      transplantation.

PMID- 30236838
TI  - Porous PEEK improves the bone-implant interface compared to plasma-sprayed
      titanium coating on PEEK.
AB  - Polyether-ether-ketone (PEEK) is one of the most common materials used for load
      bearing orthopaedic devices due to its radiolucency and favorable mechanical
      properties. However, current smooth-surfaced PEEK implants can lead to fibrous
      encapsulation and poor osseointegration. This study compared the in vitro and in
      vivo bone response to two smooth PEEK alternatives: porous PEEK and plasma
      sprayed titanium coatings on PEEK. MC3T3 cells were grown on smooth PEEK, porous
      PEEK, and Ti-coated PEEK for 14 days and assayed for calcium content,
      osteocalcin, VEGF and ALP activity. Osseointegration was investigated by
      implanting cylindrical implants into the proximal tibiae of male Sprague Dawley
      rats for 8 weeks. Bone-implant interfaces were evaluated using MUCT, histology
      and pullout testing. Cells on porous PEEK surfaces produced more calcium,
      osteocalcin, and VEGF than smooth PEEK and Ti-coated PEEK groups. Bone ingrowth
      into porous PEEK surfaces was comparable to previously reported porous materials
      and correlated well between MUCT and histology analysis. Porous PEEK implants
      exhibited greater pullout force, stiffness and energy-to-failure compared to
      smooth PEEK and Ti-coated PEEK, despite Ti-coated PEEK exhibiting a high degree
      of bone-implant contact. These results are attributed to increased mechanical
      interlocking of bone with the porous PEEK implant surface. Overall, porous PEEK
      was associated with improved osteogenic differentiation in vitro and greater
      implant fixation in vivo compared to smooth PEEK and Ti-coated PEEK. These
      results suggest that not all PEEK implants inherently generate a fibrous response
      and that topography has a central role in determining implant osseointegration.

PMID- 30236839
TI  - A self-healing hydrogel as an injectable instructive carrier for cellular
      morphogenesis.
AB  - Transplantation of progenitor cells can accelerate tissue healing and
      regenerative processes. Nonetheless, direct cell delivery fails to support
      survival of transplanted cells or long-term treatment of vascular related
      diseases due to compromised vasculature and tissue conditions. Using injectable
      hydrogels that cross-link in situ, could protect cells in vivo, but their sol-gel
      transition is time-dependent and difficult to precisely control. Hydrogels with
      self-healing properties are proposed to address these limitations, yet current
      self-healing hydrogels lack bio-functionality, hindering the morphogenesis of
      delivered cells into a tissue structure. Here we establish a gelatin (Gtn)-based
      self-healing hydrogel cross-linked by oxidized dextran (Odex) as an injectable
      carrier for delivery of endothelial progenitors. The dynamic imine cross-links
      between Gtn and Odex confer the self-healing ability to the Gtn-l-Odex hydrogels
      following syringe injection. The self-healing Gtn-l-Odex not only protects the
      progenitors from injected shear force but it also allows controllable
      spatial/temporal placement of the cells. Moreover, owing to the cell-adhesive and
      proteolytic sites of Gtn, the Gtn-l-Odex hydrogels support complex vascular
      network formation from the endothelial progenitors, both in vitro and in vivo.
      This is the first report of injectable, self-healing hydrogels with biological
      properties promoting vascular morphogenesis, which holds great promise for
      accelerating the success of regenerative therapies.

PMID- 30236841
TI  - Assessment of the ecotoxicological impact of natural and synthetic beta-triketone
      herbicides on the diversity and activity of the soil bacterial community using
      omic approaches.
AB  - The emergence of pesticides of natural origin appears as an environmental
      friendly alternative to synthetic pesticides for managing weeds. To verify this
      assumption, leptospermone, a natural beta-triketone herbicide, and sulcotrione, a
      synthetic one, were applied to soil microcosms at 0* (control), 1* or 10*
      recommended field dose. The fate of these two herbicides (i.e. dissipation and
      formation of transformation products) was monitored to assess the scenario of
      exposure of soil microorganisms to natural and synthetic herbicides.
      Ecotoxicological impact of both herbicides was explored by monitoring soil
      bacterial diversity and activity using next-generation sequencing of 16S rRNA
      gene amplicons and soil metabolomics. Both leptospermone and sulcotrione fully
      dissipated over the incubation period. During their dissipation, transformation
      products of natural and synthetic beta-triketone were detected. Hydroxy
      leptospermone was almost completely dissipated by the end of the experiment,
      while CMBA, the major metabolite of sulcotrione, remained in soil microcosms.
      After 8 days of exposure, the diversity and structure of the soil bacterial
      community treated with leptospermone was significantly modified, while less
      significant changes were observed for sulcotrione. For both herbicides, the
      diversity of the soil bacterial community was still not completely recovered by
      the end of the experiment (45 days). The combined use of next-generation
      sequencing and metabolomic approaches allowed us to assess the ecotoxicological
      impact of natural and synthetic pesticides on non-target soil microorganisms and
      to detect potential biomarkers of soil exposure to beta-triketones.

PMID- 30236840
TI  - Mucus-penetrating budesonide nanosuspension enema for local treatment of
      inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal
      disorder that affects more than 1 million individuals in the USA. Local therapy
      with enema formulations, such as micronized budesonide (Entocort(r)), is a common
      strategy for treating patients with distally active IBD. However, we hypothesize
      that micronized particulates are too large to effectively penetrate colorectal
      mucus, limiting the extent of drug delivery to affected tissues prior to
      clearance. Here, we describe the development of a budesonide nanosuspension (NS)
      with the appropriate surface coating and size to enhance penetration of
      colorectal mucus and ulcerated colorectal tissues. We demonstrate that model
      fluorescent polystyrene (PS) particles ~200 nm in size with a muco-inert Pluronic
      F127 coating provide enhanced mucosal distribution and tissue penetration in mice
      with trinitrobenzenesulfonic acid (TNBS)-induced IBD compared to model 2 MUm PS
      particles coated with polyvinylpyrollidone (PVP), the stabilizer used in the
      clinical micronized budesonide formulation. We then used a wet-milling process to
      develop a budesonide NS formulation with a muco-inert Pluronic F127 coating
      (particle size ~230 nm), as well as a budesonide microsuspension (MS) stabilized
      with PVP (particle size ~2 MUm). Using an acute TNBS mouse model of IBD, we show
      that daily budesonide NS enema treatment resulted in a significant reduction in
      the macroscopic (decreased colon weight) and microscopic (histology score)
      symptoms of IBD compared to untreated controls or mice treated daily with the
      budesonide MS enema. Further, we show that the budesonide NS enema treated mice
      had a significantly reduced number of inflammatory macrophages and IL-beta
      producing CD11b + cells in colon tissue compared to untreated controls or mice
      treated with the budesonide MS enema. We conclude that the nano-size and muco
      inert coating allowed for enhanced local delivery of budesonide, and thus, a more
      significant impact on local colorectal tissue inflammation.

PMID- 30236843
TI  - Environmental health in southwestern Atlantic coral reefs: Geochemical, water
      quality and ecological indicators.
AB  - Climate change, pollution and increased runoff are some of the main drivers of
      coral reefs degradation worldwide. However, the occurrence of runoff and marine
      pollution, as well as its ecological effects in South Atlantic coral reefs are
      still poorly understood. The aim of the present work is to characterize the
      terrigenous influence and contamination impact on the environmental health of
      five reefs located along a gradient of distance from a river source, using
      geochemical, water quality, and ecological indicators. Stable isotopes and
      sterols were used as geochemical indicators of sewage and terrigenous organic
      matter. Dissolved metal concentrations (Cu, Zn, Cd, and Pb) were used as
      indicators of water quality. Population density, bleaching and chlorophyll alpha
      content of the symbiont-bearing foraminifer Amphistegina gibbosa, were used as
      indicators of ecological effects. Sampling was performed four times during the
      year to assess temporal variability. Sediment and water quality indicators showed
      that reefs close to the river discharge experience nutrient enrichment and sewage
      contamination, and metals concentrations above international environmental
      quality guidelines. Higher levels of contamination were strongly related to the
      higher frequency of bleaching and lower density in A. gibbosa populations. The
      integrated evaluation of stable isotopes, sterols and metals provided a
      consistent diagnostic about sewage influence on the studied reefs. Additionally,
      the observed bioindicator responses evidenced relevant ecological effects. The
      water quality, geochemical and ecological indicators employed in the present
      study were effective as biomonitoring tools to be applied in reefs worldwide.

PMID- 30236842
TI  - NDVI, 137Cs and nutrients for tracking soil and vegetation development on glacial
      landforms in the Lake Paron Catchment (Cordillera Blanca, Peru).
AB  - The present dominant trend of retreating and shrinking glaciers is leading to the
      formation of new soil in proglacial zones. The Cordillera Blanca located in the
      Peruvian Andes includes the Lake Paron catchment known for the Artesonraju
      Glacier and its rapid retreat, forming the largest proglacial lake in the region.
      This work aims to gain knowledge of soil and vegetation development on the most
      representative proglacial landforms existing in the Paron catchment. Previous
      research in proglacial environments suggests that soil properties might indicate
      different ages of ice retreat besides the normalised difference vegetation index
      (NDVI), which is known to be a powerful tool for assessing vegetation
      development. In the area surrounding Lake Paron up to the glacier tongue, an
      altitudinal transect (4200-4700 m a.s.l.) was established for sampling topsoils.
      A total of 40 surface soil samples (0-3 cm) were collected from the main glacial
      landforms, moraines, colluvium, glacio-fluvial terraces and alluvial fans,
      developed after different stages of glacier retreat. Soil organic carbon (SOC)
      and SOC fractions (active and stable), total nitrogen (TN) and 137Cs were
      analysed. A multitemporal analysis of NDVI was performed to assess the vegetation
      dynamics in the Paron catchment and over the different glacial landforms over
      time (1987-2018). The NDVI increase in recent decades indicates an expansion of
      vegetation cover and density. We compared NDVI values with the SOC and TN content
      to assess the relationships with vegetation growth in mountain soils. NDVI and
      the distribution of SOC and TN content show a positive correlation between
      vegetation evolution and the enrichment in soil nutrients that are more abundant
      in older moraines in coincidence with highest NDVI. These results outline the
      effect of shrinking mountain glaciers on generating new soils in parallel with
      the growth of vegetation.

PMID- 30236844
TI  - The biodegradation of cefuroxime, cefotaxime and cefpirome by the synthetic
      consortium with probiotic Bacillus clausii and investigation of their potential
      biodegradation pathways.
AB  - Cephalosporin residues in the environment are a great concern, but bioremediation
      options do exist. Bacillus clausii T reached a removal rate of 100% within 8 h
      when challenged with a mixture of cefuroxime (CFX), cefotaxime (CTX), and
      cefpirome (CPR). The co-culture of B. clausii T and B. clausii O/C displayed a
      higher removal efficiency for the mixture of CFX, CTX and CPR than a pure culture
      of B. clausii O/C. B. clausii T alleviated the biotoxicity of CFX and CPR. What's
      more, the biotoxicity of for CFX and CPR transformation products released by the
      co-culture of B. clausii T and B. clausii O/C was lower than that in pure
      cultures. Real-time PCR was applied to detect the changes in the expression
      levels of the relevant antibiotic-resistance genes of B. clausii T during CFX and
      CPR degradation. The results indicated that CFX and CPR enhanced the expression
      of the beta-lactamase gene bcl1. Hydrolysis, deacetylation and decarboxylation
      are likely the major mechanisms of CTX biodegradation by B. clausii. These
      results demonstrate that B. clausii T is a promising strain for the
      bioremediation of environmental contamination by CFX, CTX, and CPR.

PMID- 30236845
TI  - Mass transfer affects reactor performance, microbial morphology, and community
      succession in the methane-dependent denitrification and anaerobic ammonium
      oxidation co-culture.
AB  - Denitrifying anaerobic methane oxidation (DAMO) combining anaerobic ammonium
      oxidation (Anammox) process is a novel nitrogen removal technology. However, the
      roles of methane transfer (gas phase) and nitrogen transfer (liquid phase) in the
      heterogeneous process remain unclear. In this study, granular DAMO and Anammox co
      cultures were inoculated from a hollow-fiber membrane bioreactor into a sequence
      batch reactor (SBR). Since the methane transfer became limited in SBR, the
      nitrate removal rate first decreased and then increased to 10 mg/(L?day), while
      the ammonium removal rate did not recover and was around 2 mg/(L?day). The
      activity of DAMO archaea and Anammox bacteria decreased noticeably. Furthermore,
      granular aggregates dispersed into small granules and ultimately became flocs
      with poor settleability in SBR. The content of extracellular polymeric substances
      decreased, especially that of proteins and humics. DAMO archaea decreased by
      94.6% and Anammox bacteria decreased by 72%. In summary, the limitation of
      methane transfer affected DAMO and Anammox processes more notably than nitrogen
      transfer, resulting in lower nitrogen removal, granule disruption, and microbial
      community succession.

PMID- 30236847
TI  - Resistance training frequency and skeletal muscle hypertrophy: A review of
      available evidence.
AB  - OBJECTIVES: Current reviews and position stands on resistance training (RT)
      frequency and associated muscular hypertrophy are based on limited evidence
      holding implications for practical application and program design. Considering
      that several recent studies have shed new light on this topic, the present paper
      aimed to collate the available evidence on RT frequency and the associated effect
      on muscular hypertrophy. DESIGN: Review article. METHODS: Articles for this
      review were obtained through searches of PubMed/MEDLINE, Scopus, and SPORTDiscus.
      Both volume-equated (studies in which RT frequency is the only manipulated
      variable) and non-volume-equated (studies in which both RT frequency and volume
      are the manipulated variables) study designs were considered. RESULTS: Ten
      studies were found that used direct site-specific measures of hypertrophy, and,
      in general, reported that RT once per week elicits similar hypertrophy compared
      to training two or three times per week. In addition, 21 studies compared
      different RT frequencies and used lean body mass devices to estimate muscular
      growth; most of which reported no significant differences between training
      frequencies. Five studies were identified that used circumference for estimating
      muscular growth. These studies provided findings that are difficult to interpret,
      considering that circumference is a crude measure of hypertrophy (i.e., it does
      not allow for the differentiation between adipose tissue, intracellular fluids,
      and muscle mass). CONCLUSIONS: Based on the results of this review, it appears
      that under volume-equated conditions, RT frequency does not seem to have a
      pronounced effect of gains in muscle mass.

PMID- 30236846
TI  - Are exercise professionals fit to provide nutrition advice? An evaluation of
      general nutrition knowledge.
AB  - OBJECTIVES: Registered exercise professionals (REP) are trained to provide
      structured exercise recommendations and general nutrition advice to healthy
      clients. However REP provide specific nutrition advice beyond their scope of
      practice, including diet-disease advice. The present study aims to investigate
      the level of general nutrition knowledge of REP, and compare this to a sample of
      community members (CTM), and university trained dietitians (DN). DESIGN: Age
      matched REP, CTM and DN were recruited to complete the previously validated
      revised-general nutrition knowledge questionnaire. METHODS: Total nutrition
      knowledge score and section scores were compared between REP, CTM and DN. The
      impact of sex, age, level of education, and years' experience on nutrition
      knowledge was investigated. RESULTS: A total of 554 participants completed the
      questionnaire (REP, n=161; CTM, n=357; DN, n=36). The DN group performed
      significantly better overall (DN, 91.2+/-4.6; REP, 78.4+/-9.6; CTM, 75.4+/-11.3)
      and for knowledge of dietary guidelines (DN, 82.3+/-20.7; REP, 80.5+/-15.5; CTM,
      80.0+/-14.1), nutrient content of foods (DN, 92.6+/-4.4; REP, 80.9+/-9.9; CTM,
      75.7+/-12.0), and diet-disease relationships (DN, 91.4+/-9.7; REP, 65.4+/-18.0;
      CTM, 68.6+/-11.1) compared to the REP and CTM groups (p<0.001). Sex, education
      and age were all significant predictors of total nutrition knowledge (p<0.0005).
      CONCLUSIONS: Total nutrition knowledge and knowledge of diet-disease
      relationships is limited in REP. Encouraging REP to work collaboratively with a
      multidisciplinary team, including DN, will assist in providing optimal client
      care in achieving health and body composition related goals.

PMID- 30236848
TI  - The effect of sildenafil on rats with adenine-Induced chronic kidney disease.
AB  - The erectile dysfunction drug sildenafil has cardiopulmonary protective actions,
      and a nephroprotective action in cisplatin and ischemia-reperfusion-induced acute
      kidney injury. Here, we assessed its possible ameliorative action in a model of
      chronic kidney disease (CKD) using adenine feeding. Eight groups of rats were
      treated with saline (controls), adenine (0.25% w/w in feed daily for 5 weeks),
      and oral sildenafil (0.1, 0.5 or 2.5 mg/kg), either alone, or concomitantly with
      adenine. Urine was collected 24 h after the end of the treatments from all rats
      and blood pressure measured, followed by collection of blood and kidneys for the
      measurement of several functional, biochemical and histopathological parameters.
      Adenine treatment reduced body weight, creatinine renal clearance, and increased
      water intake and urine output, as well as the plasma concentrations of urea and
      creatinine, neutrophil gelatinase-associated lipocalin, and N-acetyl-beta-D
      glucosaminidase activity, and albumin in urine. Adenine also increased the
      concentrations of the uremic toxins indoxyl sulfate, uric acid and phosphate, and
      a number of proteins and inflammatory cytokines, and decreased that of several
      anti - oxidant indices. Renal histopathological markers of damage (inflammation
      and fibrosis) were significantly increased by adenine. Sildenafil, given
      simultaneously with adenine, induced a dose - dependent improvements in most of
      the above parameters, suggesting its possible use as adjunct treatment for CKD in
      humans.

PMID- 30236849
TI  - Molecular mechanisms of the action of Arctigenin in cancer.
AB  - Since antediluvian times, the scientific community has realized that natural
      compounds exhibit enormous potential for the treatment of terrible diseases, such
      as cancer. Despite a variety of effective bioactive molecules, effective
      therapies still need to be developed to treat cancer. Hence, it is necessary to
      study the interactions of natural molecules with their cellular targets.
      Arctigenin (ATG), a natural lignan compound extracted from Arctium lappa,
      inhibits the growth of various cancer cells, such as those of the stomach, lungs,
      liver, and colon, as well as leukocytes, and regulates numerous intracellular
      activities, such as antioxidative, anti-inflammatory, and anticancer activities.
      The intention of this paper is to summarize and generally analyse the molecular
      pathways that are involved in the anticancer effects of ATG. In addition, the
      interactions of ATG with other drugs are also highlighted in this paper.

PMID- 30236850
TI  - Antinociceptive activity of ethanolic extract of Azadirachta indica A. Juss
      (Neem, Meliaceae) fruit through opioid, glutamatergic and acid-sensitive ion
      pathways in adult zebrafish (Danio rerio).
AB  - Neem fruit (Azadirachta indica A. Juss.) are popularly used to treat infections,
      diarrhea, fever, bronchitis, skin diseases, infected burns and hypertension.
      Although the antinociceptive and anti-inflammatory potential of A. indica has
      already been investigated in experimental models of pain and inflammation in
      mice, the current research is the first to report the evaluation of the capacity
      of A. indica fruit ethanolic extract (EtFrNeem) in acute pain attenuation using
      the adult zebrafish (Danio rerio) as an alternative model to the use in rodents.
      EtFrNeem was submitted to antioxidant action, preliminary chemical prospecting,
      FT-IR and determination of phenol and flavonoid content tests. Subsequently,
      EtFrNeem was tested for acute nociception and abdominal inflammation, locomotor
      activity, and acute toxicity in adult zebrafish. Possible neuromodulation
      mechanisms were also evaluated. EtFrNeem showed low antioxidant activity, but was
      shown to be rich in flavonoids. EtFrNeem showed no anti-inflammatory action, did
      not alter the locomotor system, and it was not toxic. However, EtFrNeem
      significantly reduced the nociceptive behavior induced by formalin, glutamate and
      acidic saline, when compared to the control group. These effects of EtFrNeem were
      significantly similar to those of morphine, used as a positive control. The
      antinociceptive effect of EtFrNeem was inhibited by naloxone, ketamine and
      amiloride. EtFrNeem has the pharmacological potential for acute pain treatment
      and this effect is modulated by the opioid system, NMDA receptors and ASICs
      channels. These results lead us to studies of isolation and characterization of
      EtFrNeem bioactive principles, using adult zebrafish as an experimental model.

PMID- 30236851
TI  - Concentrated hot water-infusion of phragmanthera incana improves muscle glucose
      uptake, inhibits carbohydrate digesting enzymes and abates Fe2+-induced oxidative
      stress in hepatic tissues.
AB  - Chronic hyperglycemia has been implicated in the development of oxidative stress
      and as a major factor in etiology of secondary complication in diabetes. In the
      present study, the antidiabetic potential of Phragamenthra incana (P. incana) hot
      infusion and its possible inhibitory effects on carbohydrate digesting enzymes,
      promotion of muscle glucose uptake, and the antioxidative potentials in Fe2+
      induced oxidative stress in hepatic tissue were investigated. The infusion
      significantly (p < 0.05) scavenged free radicals (DPPH) and displayed favourable
      ferric reducing antioxidant power (FRAP) with increasing concentrations. It also
      significantly ameliorated Fe2+-induced oxidative stress in hepatic tissues by
      increasing superoxide dismutase (SOD) and catalase activities and depleting
      malondialdehyde (MDA) level. The results further showed that the infusion
      significantly (p < 0.05) inhibited alpha-amylase and alpha-glucosidase activity,
      and enhanced muscle glucose uptake, with and without insulin. Liquid
      Chromatography-Mass Spectroscopy (LCMS) analysis of the infusion revealed the
      presence of 2-methoxythiazole; l-cysteine; nicotinic acid; S-methyl-l-cysteine;
      isoquinoline, 1-methyl-; and 1H-indole-2,3-dione,5-methyl. The results of this
      study suggest that the observed antidiabetic and antioxidative potentials of P.
      incana could be attributed to its identified phytochemical constituents, however,
      this supports folkloric medicinal use of this plant.

PMID- 30236852
TI  - Protective effects of Kangxian ruangan capsule against nonalcoholic fatty liver
      disease fibrosis in rats induced by MCD diet.
AB  - Kangxian ruangan (KXRG) capsule is a classical formula containing various herbals
      that play a vital role of replenishing spleen and warming Yang. Traditional
      Chinese medicine believes that insufficiency of the spleen, damp-heat, and phlegm
      and stasis are the key factors to nonalcoholic fatty liver disease (NAFLD). The
      objective of this study was to investigate the effects of KXRG capsule on NAFLD
      fibrosis rats induced by MCD diet. The liver functions (ALT, AST and GGT) and
      levels of blood lipids (CHOL and TG) in each treatment group rats were
      significantly decreased, especially those in H-KXRG group. At the same time, the
      KXRG capsule alleviated the inflammatory response, histopathological changes and
      liver fibrosis of NAFLD fibrosis rats. In addition, the apoptosis of liver cells
      induced by diet was obvious via TUNEL staining. However, KXRG capsule reversed
      that negative change. Moreover, the levels of pro-apoptotic proteins (Caspase 3,
      8, 9 and Bax) were reduced by exposure to KXRG capsule, except that the anti
      apoptotic proteins (Bcl-2 and Bcl-XL) were elevated. In conclusion, KXRG relieved
      the progression of NAFLD fibrosis via maintaining the balance of TNF-alpha/IL-10
      further relieving the inflammatory reaction, and regulating the balance of Bcl
      2/Bax or Bcl-XL/Bax in a positive direction further activating damaged
      hepatocytes.

PMID- 30236854
TI  - Robotic-assisted vs. open radical prostatectomy: A machine learning framework for
      intelligent analysis of patient-reported outcomes from online cancer support
      groups.
AB  - BACKGROUND: The advantages of Robot-assisted laparoscopic prostatectomy (RARP)
      over open radical prostatectomy (ORP) in Prostate cancer perioperatively are well
      established, but quality of life is more contentious. Increasingly, patients are
      utilising online cancer support groups (OCSG) to express themselves. Currently
      there is no method of analysis of these sophisticated data sources. We have used
      the PRIME-2 (Patient Reported Information Multidimensional Exploration version 2)
      framework for automated identification and intelligent analysis of decision
      making, functional and emotional outcomes in men undergoing ORP vs. RARP from
      OCSG discussions. METHODS: The PRIME-2 framework was developed to retrospectively
      analyse individualised patient-reported information from 5,157 patients
      undergoing RARP and 579 ORP. The decision factors, side effects, and emotions in
      2 groups were analysed and compared using Chi-squared, t tests, and Pearson
      correlation. RESULTS: There were no differences in Gleason score, Prostate
      Specific Antigen (PSA), and age between the groups. Surgeon experience and
      preservation of erectile function (P < 0.01) were important factors in the
      decision making process. There were no significant differences in urinary,
      sexual, or bowel symptoms between ORP and RARP on a monthly basis during the
      initial 12 months. Emotions expressed by patients undergoing RARP were more
      consistent and positive while ORP expressed more negative emotions at the time of
      surgery and 3 months postsurgery (P < 0.05), due to pain and discomfort, and
      during ninth month due to fear and anxiety of pending PSA tests. CONCLUSIONS: ORP
      and RARP demonstrated similar side effect profiles for 12 months, but PRIME-2
      enables identification of important quality of life features and emotions over
      time. It is timely for clinicians to accept OCSG as an adjunct to Prostate cancer
      care.

PMID- 30236853
TI  - Self-reported Black race predicts significant prostate cancer independent of
      clinical setting and clinical and socioeconomic risk factors.
AB  - INTRODUCTION AND OBJECTIVE: Studies have linked Black race to prostate cancer
      (CaP) risk but most fail to account for established risk factors such as 5-ARI
      use, prostate volume, socioeconomic status, and hospital setting. We assess
      whether Black race remains associated with CaP and Gleason >=3 + 4 CaP, after
      adjusting for clinical setting and socioeconomic and clinical factors at prostate
      biopsy, with a focus on men aged 40-54 years, who may be excluded from current
      screening guidelines. METHODS: We recruited 564 men age 40-79 undergoing initial
      prostate biopsy for abnormal PSA or digital rectal examination (DRE) from three
      publicly funded and two private hospitals from 2009-2014. Univariate and
      multivariate analyses examined the associations between hospital type, race, West
      African Ancestry (WAA), clinical, and sociodemographic risk factors with CaP
      diagnosis and Gleason >=3 + 4 CaP. Given changes in CaP screening
      recommendations, we also assess the multivariate analyses for men aged 40-54.
      RESULTS: Black and White men had similar age, BMI, and prostate volume. Black men
      had higher PSA (8.10 ng/mL vs. 5.63 ng/mL) and PSA density (0.22 ng/mL/cm3 vs.
      0.15 ng/mL/cm3, all p < 0.001). Blacks had higher frequency of CaP (63.1% vs.
      41.5%, p<0.001) and Gleason >=3+4 CaP relative to Whites in both public (27.7% vs
      11.6%, p<0.001) and private (48.4% vs 21.6%, p = 0.002) settings. In models
      adjusted for age, first degree family history, prostate volume, 5-ARI use,
      hospital type, income, marital and educational status, Black race was
      independently associated with overall CaP diagnosis (OR = 2.13, p = 0.002). There
      was a significant multiplicative interaction with Black race and abnormal DRE for
      Gleason >=3 + 4 CaP (OR = 2.93, p = 0.01). WAA was not predictive of overall or
      significant CaP among Black men. Black race (OR = 5.66, p = 0.02) and family
      history (OR = 4.98, p = 0.01) were independently positively associated with
      overall CaP diagnosis for men aged 40 to 54. CONCLUSIONS: Black race is
      independently associated with CaP and Gleason >=3+4 CaP after accounting for
      clinical and socioeconomic risk factors including clinical setting and WAA, and
      has a higher odds ratio of CaP diagnosis in younger men. Further investigation
      into optimizing screening in Black men aged 40 to 54 is warranted.

PMID- 30236855
TI  - Immediate intravesical chemotherapy for low-grade bladder tumors in California:
      An underutilized practice and its impact on recurrence.
AB  - OBJECTIVES: To demonstrate patterns of uptake and impact on recurrence of
      intravesical chemotherapy (IC) immediately following transurethral resection of
      bladder tumor (TURBT) for low-grade non-muscle-invasive bladder cancer (NMIBC) at
      a population level. METHODS: Incident cases of low-grade (LG) Ta or T1 NMIBC from
      2005 to 2012 were identified from the California Cancer Registry. We determined
      rates of IC utilization following TURBT. Multivariable logistic regression models
      were utilized to assess predictors of IC utilization. Multivariable Cox
      proportional hazards regression was used to assess the association of IC
      utilization with recurrence-free survival, bladder cancer-specific survival, and
      overall survival. RESULTS: Ten thousand thirty-one patients with LG NMIBC
      diagnosed in California between 2005 and 2012. The overall rate of IC utilization
      was 5.1%, and increased from 1.7% (2005-2006) to 9.6% (2011-2012). More recent
      year of diagnosis (Odds ratio 1.74, confidence interval 1.60-1.90 for 2-year
      increments) was associated with an increased likelihood of undergoing immediate
      postoperative IC. The cumulative incidence of recurrence at 24 months for
      patients who received IC was 25.2% compared to 30.2% among those who did not
      receive IC. Use of IC was significantly associated with improved recurrence-free
      survival (Hazards ratio 0.82, confidence interval 0.70-0.97). CONCLUSION:
      Utilization of IC for LG NMIBC remains dismally low, with less than 10% of
      patients receiving this standard of care. Low utilization is associated with
      increased rates of recurrence. We demonstrate a major shortcoming in quality of
      care with potential widespread impact on outcomes and cost of care.

PMID- 30236856
TI  - Juvenile scurvy from Late Medieval Knin, Croatia.
AB  - In this study, we examine the scurvy associated skeletal lesions among juveniles
      from the late Medieval site Uzdolje-Grablje in Croatia. The study aims to
      establish a demographic pattern of scurvy using existing diagnostic criteria. The
      sample consists of 16 well-preserved and fairly complete juveniles, excavated
      from a cemetery dating to 1420-1920. Skeletal remains were analyzed
      macroscopically for signs of porosity and new bone formation. Scurvy is diagnosed
      using the "Ortner criteria" of cranial and postcranial lesions. Depending on the
      location of the lesions, individuals were diagnosed with either scurvy or
      possible scurvy. Half of the individuals in our sample are diagnosed with scurvy,
      with additional 25% being diagnosed with possible scurvy. Along with porotic
      lesions, all individuals diagnosed with scurvy/possible scurvy showed new bone
      formation on at least one skeletal element. The occurrence of lesions associated
      with scurvy in our sample is unusually high. Instead of focusing solely on diet
      and insufficient intake of the vitamin C, a more likely explanation lies in the
      synergy between diet, exposure to infections, and the environment.

PMID- 30236857
TI  - Research Mentoring of Medical Students: A Win-Win.

PMID- 30236859
TI  - Using Emotional Intelligence Helps Women Build Trust and Grow Influence.

PMID- 30236858
TI  - Radiologist Burnout Is Not Just Isolated to the United States: Perspectives From
      Canada.

PMID- 30236860
TI  - Insights into the physiology of ammonia-oxidizing microorganisms.
AB  - Nitrification is the aerobic process of the nitrogen cycle that converts ammonia
      to nitrate and is facilitated by ammonia-oxidizing and nitrite-oxidizing
      microorganisms. Ammonia-oxidizers are unique chemolithotrophs that evolved
      specialized networks of electron carriers to generate proton motive force using
      ammonia as a sole energy source as well as mechanisms to tolerate cytotoxic
      intermediates of their metabolism. Cultivation and genome sequencing of ammonia
      oxidizing bacteria (AOB), archaea (AOA), and comammox bacteria (i.e. COMplete
      AMMonia OXidizers) have revealed new enzymology, mechanisms to tolerate low pH
      and hypoxia, and mechanisms for production of the potent greenhouse gas, nitrous
      oxide. The role of ammonia-oxidizers in natural and engineered environments is of
      keen interest as they are essential to the nitrogen cycle, wastewater treatment,
      and flux of greenhouse gases to the atmosphere.

PMID- 30236861
TI  - Path mediation analysis reveals GBA impacts Lewy body disease status by
      increasing alpha-synuclein levels.
AB  - Synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy
      bodies (DLB) are characterized by the accumulation of abnormal alpha-synuclein in
      intraneuronal inclusions, named Lewy bodies. Mutations in GBA1, the gene encoding
      the lysosomal hydrolase glucocerebrosidase, have been identified as the most
      common genetic risk factor for PD and DLB. However, despite extensive research,
      the mechanism by which glucocerebrosidase dysfunction increases the risk for PD
      or DLB still remains elusive. In our study we expand the toolbox for PD-DLB post
      mortem studies by introducing new quantitative biochemical assays for
      glucocerebrosidase and alpha-synuclein. Applying causal modelling, we determine
      how these parameters are interrelated and ultimately impact disease
      manifestation. We developed quantitative immuno-based assays for
      glucocerebrosidase and alpha-synuclein (total and phosphorylated at Serine 129)
      protein levels, as well as a liquid chromatography-mass spectrometry method for
      the detection of the glucocerebrosidase lipid substrate glucosylsphingosine.
      These assays were applied on tissue samples from frontal cortex, putamen and
      substantia nigra of PD (n = 15) and DLB (n = 15) patients and age-matched non
      demented controls (n = 15). Our results confirm elevated p-129 over total alpha
      synuclein levels in the insoluble fraction of PD and DLB post-mortem brain tissue
      and we found significantly increased alpha-synuclein levels in the soluble
      fractions in PD and DLB. Furthermore, we identified an inverse correlation
      between reduced glucocerebrosidase enzyme activity and protein levels with
      increased glucosylsphingosine levels. In the substantia nigra, a brain region
      particularly vulnerable in Parkinson's disease, we found a significant
      correlation between glucocerebrosidase protein reduction and increased p129/total
      alpha-synuclein ratios. We assessed the direction and strength of the
      interrelation between all measured parameters by confirmatory path analysis.
      Interestingly, we found that glucocerebrosidase dysfunction impacts the PD-DLB
      status by increasing alpha-synuclein ratios in the substantia nigra, which was
      partly mediated by increasing glucosylsphingosine levels. In conclusion, we show
      that the introduced immuno-based assays enable the quantitative assessment of
      glucocerebrosidase and alpha-synuclein parameters in post-mortem brain. In the
      substantia nigra, reduced glucocerebrosidase levels contribute to the increase in
      alpha-synuclein levels and to PD-DLB disease manifestation partly by increasing
      its glycolipid substrate glucosylsphingosine. This interrelation between
      glucocerebrosidase, glucosylsphingosine and alpha-synuclein parameters supports
      the hypothesis that glucocerebrosidase acts as a modulator of PD-DLB.

PMID- 30236862
TI  - The PPARGC1A locus and CNS-specific PGC-1alpha isoforms are associated with
      Parkinson's Disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease
      worldwide. PGC-1alpha, encoded by PPARGC1A, is a transcriptional co-activator
      that has been implicated in the pathogenesis of neurodegenerative disorders. We
      recently discovered multiple new PPARGC1A transcripts that initiate from a novel
      promoter located far upstream of the reference gene promoter, are CNS-specific
      and are more abundant than reference gene transcripts in whole brain. These CNS
      specific transcripts encode two main full-length and several truncated isoforms
      via alternative splicing. Truncated CNS-isoforms include 17 kDa proteins that
      lack the second LXXLL motif serving as an interaction site for several nuclear
      receptors. We now determined expression levels of CNS- and reference gene
      transcripts in 5 brain regions of 21, 8, and 13 deceased subjects with idiopathic
      PD, Lewy body dementia and controls without neurodegenerative disorders,
      respectively. We observed reductions of CNS-specific transcripts (encoding full
      length isoforms) only in the substantia nigra pars compacta of PD and Lewy body
      dementia. However, in the substantia nigra and globus pallidus of PD cases we
      found an up-regulation of transcripts encoding the 17 kDa proteins that inhibited
      the co-activation of several transcription factors by full-length PGC-1alpha
      proteins in transfection assays. In two established animal models of PD, the
      PPARGC1A expression profiles differed from the profile in human PD in that the
      levels of CNS- and reference gene transcripts were decreased in several brain
      regions. Furthermore, we identified haplotypes in the CNS-specific region of
      PPARGC1A that appeared protective for PD in a clinical cohort and a post-mortem
      sample (P = .0002). Thus, functional and genetic studies support a role of the
      CNS-specific PPARGC1A locus in PD.

PMID- 30236863
TI  - Implementation of the Safewards model in public mental health facilities: A
      qualitative evaluation of staff perceptions.
AB  - BACKGROUND: The Safewards model is gaining increasing acceptance in the mental
      health field in Australia and overseas. One of the most important goals of
      inpatient psychiatric services is to provide a safe and therapeutic environment
      for both patients and staff. However, this goal can be difficult to achieve if
      staff-patient interaction is not conducive to preventing violence and aggression.
      OBJECTIVE: The purpose of this study was to explore nursing staff perceptions of
      the factors impacting on their capacity to establish Safewards in acute adult
      inpatient wards. DESIGN: This study was guided by a phenomenological approach to
      develop a rich understanding of staff perceptions using semi-structured
      interviews. SETTING AND SAMPLE: The setting was three acute mental health wards
      attached to general hospitals; one in a large provincial hospital and two in
      metropolitan hospitals in south-east Queensland. Interview participants were a
      purposive sample of fifteen registered nurses across each of the three wards.
      METHOD: Semi-structured interviews were conducted at 12 months post
      implementation of Safewards. The study was underpinned by Michie's integrative
      framework of behaviour change that helped identify target areas in order to
      enhance successful implementation of this model. RESULTS: Content analysis of
      interview transcripts highlighted a range of factors including failure to address
      the difficulties encountered by some staff in engaging with Safewards
      interventions, lack of support from management, poor use of nurse educator time,
      the 'language' of Safewards, high acuity on the study wards, and staff and
      patient turnover. CONCLUSION: This study highlights some difficulties with
      implementing Safewards and maintaining fidelity of the Safewards interventions in
      busy acute inpatient wards. Although these findings are from a qualitative study
      consisting of only 15 staff, our results indicate that efforts to implement
      Safewards need to address challenges faced by staff in engaging with the
      interventions, ensure buy-in from management, ensure adequate training and
      support during implementation and review training materials to ensure they fit
      with the local (i.e. Australian) context. Safewards provides an opportunity for a
      change in attitudes and development of a more therapeutic ward environment.

PMID- 30236865
TI  - Glutamate-dopamine matters in psychosis.

PMID- 30236864
TI  - The relationship between cortical glutamate and striatal dopamine in first
      episode psychosis: a cross-sectional multimodal PET and magnetic resonance
      spectroscopy imaging study.
AB  - BACKGROUND: The pathophysiology of psychosis is incompletely understood.
      Disruption in cortical glutamatergic signalling causing aberrant striatal
      dopamine synthesis capacity is a proposed model for psychosis, but has not been
      tested in vivo. We therefore aimed to test the relationship between cortical
      glutamate concentrations and striatal dopamine synthesis capacity, and psychotic
      symptoms. METHODS: In this cross-sectional multimodal imaging study, 28
      individuals with first-episode psychosis and 28 healthy controls underwent 18F
      DOPA PET (measuring striatal dopamine synthesis capacity), and proton magnetic
      resonance spectroscopy (measuring anterior cingulate cortex glutamate
      concentrations). Participants were recruited from first-episode psychosis
      services in London, UK and were required to be in the first episode of a
      psychotic illness, with no previous illness or treatment episodes. Exclusion
      criteria for all participants were: history of substantial head trauma,
      dependence on illicit substances, medical comorbidity (other than minor
      illnesses), and contraindications to scanning (such as pregnancy). Symptoms were
      measured using the Positive and Negative Syndrome Scale. The primary endpoint was
      the relationship between anterior cingulate cortex glutamate concentrations and
      striatal dopamine synthesis capacity in individuals with their first episode of
      psychosis as shown by imaging, examined by linear regression. Linear regression
      was used to examine relationships between measures. FINDINGS: Glutamate
      concentrations showed a significant inverse relationship with striatal dopamine
      synthesis capacity in patients with psychosis (R2=0.16, p=0.03, beta -1.71 * 10
      4, SE 0.76 * 10-4). This relationship remained significant after the addition of
      age, gender, ethnicity, and medication status to the model (p=0.015). In healthy
      controls, there was no significant relationship between dopamine and glutamate
      measures (R2=0.04, p=0.39). Positive and Negative Syndrome Scale positive
      psychotic symptoms were positively associated with striatal dopamine synthesis
      capacity (R2=0.14, p=0.046, beta 2546, SE 1217) and showed an inverse
      relationship with anterior cingulate glutamate concentrations (R2=0.16, p=0.03,
      beta -1.71 * 10-4, SE 7.63 * 10-5). No relationships were seen with negative
      symptoms (positive symptoms, mean [SD] -18.4 (6.6) negative symptoms, mean [SD] 
      15.4 [6.1]). INTERPRETATION: These observations are consistent with the
      hypothesis that cortical glutamate dysfunction is related to subcortical dopamine
      synthesis capacity and psychosis. Although the precise mechanistic relationship
      between cortical glutamate and dopamine in vivo remains unclear, our findings
      support further studies to test the effect of modulating cortical glutamate in
      the treatment of psychosis. FUNDING: Medical Research Council, Wellcome Trust,
      Biomedical Research Council, South London and Maudsley NHS Foundation Trust, JMAS
      Sim Fellowship, Royal College of Physicians (Edinburgh) (SJ).

PMID- 30236866
TI  - Discontinuing or continuing statin following intracerebral hemorrhage from the
      view of a national cohort study.
AB  - BACKGROUND AND AIMS: Statins improve clinical outcomes in patients with ischemic
      stroke but there is no evidence of the effect of continuing long-term statin
      therapy in patients with intracerebral hemorrhage (ICH). The aim of this study
      was to evaluate the impact of continuing statin after ICH. METHODS: Data on
      patients with ICH was retrieved from the National Health Insurance Research
      Database of Taiwan. The final population was separated into two groups according
      to those who continued and those who discontinued statin treatment. All-cause
      mortality and cardiovascular outcomes were analyzed after a 3 year follow-up
      after propensity score matching (PSM). RESULTS: Of the 114,101 patients with ICH,
      who were initially enrolled, 2468 patients with dyslipidemia and ICH were
      included. After PSM, the benefit of statin therapy on mortality appeared from 1
      year to the end of the 3-year follow-up period after discharge (statin group
      versus non-statin group: 4.9% vs.12.3% at 1 year (hazard ratio [HR], 0.38; 95%
      confidence interval [CI], 0.26-0.57) and 12.9% vs. 25.3% at the end of the 3 year
      follow-up period (HR, 0.45; 95% CI, 0.35-0.58). Compared with the patients using
      lipophilic statins, those using hydrophilic statins had a significantly lower
      incidence of all-cause mortality (HR = 0.65, 95% CI = 0.43-0.99). There were no
      differences between those prescribed moderate-intensity statins and those
      prescribed high-intensity statins in terms of stroke and all-cause mortality (HR
      = 0.76; 95% CI = 0.40-1.46). CONCLUSIONS: There was a lower risk of all-cause
      mortality following ICH in patients who continued statin treatment compared with
      those without statin treatment, especially in those treated with hydrophilic
      statins.

PMID- 30236867
TI  - Platelet reactivity and coronary microvascular impairment after percutaneous
      revascularization in stable patients receiving clopidogrel or prasugrel.
AB  - BACKGROUND AND AIMS: Increased platelet reactivity (PR) associated with variable
      degree of coronary microvascular impairment has been reported in patients on
      clopidogrel after elective percutaneous coronary intervention (PCI). Prasugrel
      provides more potent platelet inhibition than clopidogrel, though it is unknown
      whether it might also prevent PCI-related platelet activation. In stable patients
      undergoing elective PCI, we compared: (1) the effects of prasugrel vs.
      clopidogrel on peri-procedural variations of PR and (2) the correlation of
      platelet inhibition potency with PCI-induced coronary microvascular impairment.
      METHODS: Forty thienopyridine-naive patients were randomly assigned to a loading
      dose of either prasugrel 60 mg (n = 20) or clopidogrel 600 mg (n = 20) at least
      12 h before PCI. At the time of PCI, we assessed adenosine diphosphate (ADP)
      induced PR with the Multiplate Analyzer, and the pressure-derived index of
      microvascular resistance (IMR) in the treated coronary, both at baseline and post
      procedure. RESULTS: ADP-induced PR was significantly lower in the prasugrel
      compared with clopidogrel group both at baseline (16.0 +/- 8.7 vs. 33.9 +/- 18.0
      aggregation units [AU], p < 0.001) and post-procedure (16.2 +/- 9.0 vs. 39.0 +/-
      18.6 AU, p < 0.001). A significant peri-procedural increase in PR was observed in
      the clopidogrel group (p = 0.008), but not in the prasugrel group (p = 0.822). A
      significant correlation was found between IMR and PR both at baseline (r = 0.458,
      p = 0.003) and post-PCI (r = 0.487, p = 0.001). CONCLUSIONS: A loading dose of
      prasugrel compared with clopidogrel is able to attenuate PCI-related increase in
      PR in patients with stable CAD undergoing PCI, which might contribute to the
      beneficial effect of this drug on peri-procedural coronary microvascular
      function.

PMID- 30236868
TI  - Expression of acetyl-histone H3 and acetyl-histone H4 in dorsal root ganglion and
      spinal dorsal horn in rat chronic pain models.
AB  - AIMS: Histone acetylation and deacetylation are two histone posttranslational
      modifications that are usually controlled by histone acetyltransferases (HATs)
      and histone deacetylases (HDACs). Although HATs or HDACs Inhibitors could relieve
      pain hypersensitivities in chronic pain animal models, it is not clear on the
      expression of global histone acetylation in the dorsal root ganglion (DRG) or
      spinal dorsal horn in chronic pain conditions. MAIN METHODS: A spinal nerve
      ligation (SNL)-induced neuropathic pain model and a complete Freund's adjuvant
      (CFA)-induced inflammatory pain model in rats were used to examine the expression
      of total acetyl-histone H3 (AcH3) and total acetyl-histone H4 (AcH4) by
      immunofluorescence or western blot. KEY FINDINGS: AcH3 and AcH4 not only
      localized in neuronal nuclei, but also in nuclei of glial cells in the DRG.
      Unilateral SNL induced the increase of AcH3 and AcH4 expression in the injured
      lumbar 5 (L5) DRG, but not in the uninjured L5 DRG or the spinal dorsal horn,
      while unilateral intraplantar injection of CFA increased AcH3 and AcH4 expression
      in the ipsilateral L4/5 spinal dorsal horn, but not in the L4/5 DRG.
      SIGNIFICANCE: These results provide morphological evidence for global histone
      acetylation expression in the DRG and spinal cord and indicate the differential
      expression in the DRG and spinal dorsal horn in different chronic pain models.
      More precise epigenetic mechanisms of histone acetylation on the target genes
      need to be revealed.

PMID- 30236869
TI  - The role of orphan G protein-coupled receptors in the modulation of pain: A
      review.
AB  - G protein-coupled receptors (GPCRs) comprise a large number of receptors. Orphan
      GPCRs are divided into six families. These groups contain orphan receptors for
      which the endogenous ligands are unclear. They have various physiological effects
      in the body and have the potential to be used in the treatment of different
      diseases. Considering their important role in the central and peripheral nervous
      system, their role in the treatment of pain has been the subject of some recent
      studies. At present, there are effective therapeutics for the treatment of pain
      including opioid medications and non-steroidal anti-inflammatory drugs. However,
      the side effects of these drugs and the risks of tolerance and dependence remain
      a major problem. In addition, neuropathic pain is a condition that does not
      respond to currently available analgesic medications well. In the present review
      article, we aimed to review the most recent findings regarding the role of orphan
      GPCRs in the treatment of pain. Accordingly, based on the preclinical findings,
      the role of GPR3, GPR7, GPR8, GPR18, GPR30, GPR35, GPR40, GPR55, GPR74, and
      GPR147 in the treatment of pain was discussed. The present study highlights the
      role of orphan GPCRs in the modulation of pain and implies that these receptors
      are potential new targets for finding better and more efficient therapeutics for
      the management of pain particularly neuropathic pain.

PMID- 30236870
TI  - Intestinal anti-inflammatory effect of the probiotic Saccharomyces boulardii in
      DSS-induced colitis in mice: Impact on microRNAs expression and gut microbiota
      composition.
AB  - The beneficial effects exerted by probiotics in inflammatory bowel disease (IBD)
      are well known, although their exact mechanisms have not been fully elucidated,
      and only few studies have focused on their impact on selected miRNAs and the gut
      microbiota composition. Therefore, our aim was to correlate the intestinal anti
      inflammatory activity of the probiotic Saccharomyces boulardii in the dextran
      sodium sulphate (DSS) model of mouse colitis and the changes induced in miRNA
      expression and gut microbiota populations. Probiotic was given orally (5*109 CFU)
      to C57BL/6 mice for 26 days. After 2 weeks, the colitis was induced adding DSS to
      the drinking water. Mice were scored daily using a Disease Activity Index (DAI).
      After sacrifice, the colonic specimens were evaluated by determining the
      expression of inflammatory markers and micro-RNAs by qRT-PCR. Moreover, changes
      in microbiota populations were evaluated by pyrosequencing. Probiotic ameliorated
      the colonic damage induced by DSS, as evidenced by lower DAI values and colonic
      weight/length compared with untreated mice. The treatment modified the colonic
      expression of different inflammatory markers and the epithelial integrity
      proteins, and induced changes in micro-RNAs expression. Moreover, microbiota
      characterization showed that probiotic treatment increased bacterial diversity,
      thus ameliorating the dysbiosis produced by DSS-colitis. Saccharomyces boulardii
      exerted intestinal anti-inflammatory effects in DSS-mouse colitis, through the
      modulation in the immune response, involving modification of altered miRNA
      expression, being associated to the improvement of the inflammation-associated
      dysbiosis in the intestinal lumen, which could be of great interest to control
      the complex pathogenesis of IBD.

PMID- 30236871
TI  - Dietary supplementation with alkylresorcinols prevents muscle atrophy through a
      shift of energy supply.
AB  - It has been reported that phytoextracts that contain alkylresorcinols (ARs)
      protect against severe myofibrillar degeneration found in isoproterenol-induced
      myocardial infarction. In this study, we examined the effect of dietary ARs
      derived from wheat bran extracts on muscle atrophy in denervated mice. The mice
      were divided into the following four groups: (1) sham-operated (control) mice fed
      with normal diet (S-ND), (2) denervated mice fed with normal diet (D-ND), (3)
      control mice fed with ARs-supplemented diet (S-AR) and (4) denervated mice fed
      with ARs-supplemented diet (D-AR). The intake of ARs prevented the denervation
      induced reduction of the weight of the hind limb muscles and the myofiber size.
      However, the expression of ubiquitin ligases and autophagy-related genes, which
      is associated with muscle proteolysis, was slightly higher in D-AR than in D-ND.
      Moreover, the abundance of the autophagy marker p62 was significantly higher in D
      AR than in D-ND. Muscle atrophy has been known to be associated with a disturbed
      energy metabolism. The expression of pyruvate dehydrogenase kinase 4 (PDK4),
      which is related to fatty acid metabolism, was decreased in D-ND as compared with
      that in S-ND. In contrast, dietary supplementation with ARs inhibited the
      decrease of PDK4 expression caused by denervation. Furthermore, the abnormal
      expression pattern of genes related to the abundance of lipid droplets-coated
      proteins that was induced by denervation was improved by ARs. These results raise
      the possibility that dietary supplementation with ARs modifies the disruption of
      fatty acid metabolism induced by lipid autophagy, resulting in the prevention of
      muscle atrophy.

PMID- 30236872
TI  - Arginine promotes skeletal muscle fiber type transformation from fast-twitch to
      slow-twitch via Sirt1/AMPK pathway.
AB  - This study investigated the effect of arginine on skeletal muscle fiber type
      transformation in mice and in C2C12 myotubes. Our data showed that dietary
      supplementation of arginine in mice significantly up-regulated the slow myosin
      heavy chain (MyHC), troponin I-SS, sirtuin1 (Sirt1) and peroxisome proliferator
      activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expressions, as
      well as significantly down-regulated the fast MyHC protein expression. In C2C12
      myotubes, arginine significantly increased the protein level of slow MyHC and the
      number of slow MyHC-positive cells, as well as significantly decreased the
      protein level of fast MyHC and the number of fast MyHC-positive cells. We also
      showed that arginine increased the activities of succinic dehydrogenase and
      malate dehydrogenase and decreased the activity of lactate dehydrogenase in mice
      and in C2C12 myotubes. Here we found that AMP-activated protein kinase (AMPK) was
      activated by arginine in mice and in C2C12 myotubes. However, inhibition of AMPK
      activity by compound C significantly attenuated the effects of arginine on slow
      MyHC and fast MyHC expressions in C2C12 myotubes. Finally, we showed that
      inhibition of Sirt1 expression by EX527 attenuated arginine-induced increase in
      the protein levels of phospho-AMPK and slow MyHC, the mRNA level of nitric oxide
      synthase (NOS) and the contents of NOS and NO, as well as decrease in fast MyHC
      protein level. Together, our findings indicated that arginine promotes skeletal
      muscle fiber type switching from fast-twitch to slow-twitch via Sirt1/AMPK
      pathway.

PMID- 30236873
TI  - Maternal fructose induces gender-dependent changes in both LXRalpha promoter
      methylation and cholesterol metabolism in progeny.
AB  - Fructose consumption from added sugars correlates with the epidemic rise in
      obesity, metabolic syndrome and cardiovascular diseases. However, consumption of
      beverages containing fructose is allowed during gestation. We have investigated
      whether maternal fructose intake produces subsequent changes in cholesterol
      metabolism of progeny. Carbohydrates were supplied to pregnant rats in drinking
      water (10% w/v solution) throughout gestation. Adult male and female descendants
      from fructose-fed, control or glucose-fed mothers were studied. Male offspring
      from fructose-fed mothers had elevated plasma HDL-cholesterol levels, whereas
      female progeny from fructose-fed mothers presented lower levels of non-HDL
      cholesterol vs. the other two groups. Liver X-receptor (LXR), an important
      regulator of cholesterol metabolism, and its target genes such as scavenger
      receptor B1, ATP-binding cassette (ABC)G5 and cholesterol 7-alpha hydroxylase
      showed decreased gene expression in males from fructose-fed mothers and the
      opposite in the female progeny. Moreover, the expression of a number of LXRalpha
      target genes related to lipogenesis paralleled to that for LXRalpha expression.
      In accordance with this, LXRalpha gene promoter methylation was increased in
      males from fructose-fed mothers and decreased in the corresponding group of
      females. Surprisingly, plasma folic acid levels, an important methyl-group donor,
      were augmented in males from fructose-fed mothers and diminished in female
      offspring. Maternal fructose intake produces a fetal programming that influences,
      in a gender-dependent manner, the transcription factor LXRalpha epigenetically,
      and both hepatic mRNA gene expression and plasma parameters of cholesterol
      metabolism in adult progeny. Changes in the LXRalpha promoter methylation might
      be related to the availability of the methyl donor folate.

PMID- 30236874
TI  - Autologous fat grafting after breast conserving surgery: Breast imaging changes
      and patient-reported outcome.
AB  - BACKGROUND: Autologous fat grafting (AFG) to the breast is known to cause
      radiologic breast imaging changes. However, these changes have primarily been
      investigated in breast augmentation settings, whereas the radiologic breast
      imaging changes after AFG in patients who underwent breast conserving surgery
      (BCS) have been only sparsely studied. METHODS: All women scheduled to receive
      AFG to reconstruct BCS defects at our institution between 2014 and 2015 were
      eligible to participate. Before and after AFG, participants underwent radiologic
      breast imaging and completed patient-reported outcome measures for body image,
      aesthetic breast appearance, scar quality, and fear of cancer recurrence.
      Moreover, an observer evaluated changes in the aesthetic breast appearance and
      scar quality. RESULTS: Of 49 eligible patients, 42 were included. Participants
      received 1-3 AFG procedures, with a mean total grafted volume of 135 +/- 74 mL.
      Post-AFG breast imaging was performed 9 +/- 5 (range 2-25) months after the final
      AFG procedure. Comparison of pre- and post-AFG radiologic breast images revealed
      that 21% had developed calcifications, 85% had developed oil cysts, and 3% had
      developed increased scarring. Five patients presented with breast imaging changes
      that required biopsy or additional radiologic evaluation. Significant
      improvements were observed in breast aesthetic appearance, body image, and scar
      quality. No major surgical complications occurred. Minor surgical complications
      were observed in 3% of the patients. CONCLUSIONS: Using AFG to reconstruct BCS
      defects induces considerable radiologic breast imaging changes. Although the
      patients experience significant improvements in body image, breast aesthetic
      appearance, and scar quality, the long-term effect of breast imaging changes
      warrants further investigation.

PMID- 30236875
TI  - Readability and quality of breast reduction on-line resources.

PMID- 30236876
TI  - Clinical results and quality of life after reconstruction following sacrectomy
      for primary bone malignancy.
AB  - BACKGROUND: Sacrectomy is a rare and demanding surgical procedure that results in
      major soft tissue defects and spinopelvic discontinuity. No consensus is
      available on the optimal reconstruction algorithm. Therefore, the present study
      evaluated the results of sacrectomy reconstruction and its impact on patients'
      quality of life (QOL). METHODS: A retrospective chart review was conducted for 21
      patients who underwent sacrectomy for a primary bone tumour. Patients were
      divided into groups based on the timing of reconstruction as follows: no
      reconstruction, immediate reconstruction or delayed reconstruction. QOL was
      measured using the EQ-5D instrument before and after surgery in patients treated
      in the intensive care unit. RESULTS: The mean patient age was 57 (range 22-81)
      years. The most common reconstruction was gluteal muscle flap (n = 9) and gluteal
      fasciocutaneous flap (n = 4). Four patients required free-tissue transfer, three
      latissimus dorsi flaps and one vascular fibula bone transfer. No free flap losses
      were noted. The need for unplanned re-operations did not differ between groups (p
      = 0.397), and no significant differences were found for pre- and post-operative
      QOL or any of its dimensions. DISCUSSION: Free flap surgery is reliable for
      reconstructing the largest sacrectomy defects. Even in the most complex cases,
      surgery can be safely staged, and final reconstruction can be carried out within
      1 week of resection surgery without increasing peri-operative complications.
      Sacrectomy does not have an immoderate effect on the measured QOL.

PMID- 30236877
TI  - Pharmacogenomics of Alzheimer's and Parkinson's diseases.
AB  - Neurodegenerative disorders (NDDs)(Alzheimer's disease, Parkinson's disease)
      represent major problems of health in developed countries, with important
      psychosocial burden for families and high cost for the society. NDDs share some
      common pathogenic mechanisms such as age-related decline, multiple genetic
      defects distributed across the genome, deposits of abnormal proteins in the
      brain, and diverse environmental risk factors. Patients with NDDs currently
      receive polypharmacy with a high risk for drug-drug interactions and severe
      adverse drug events. Pharmacogenomics accounts for 60-90% variability in drug
      pharmacokinetics and pharmacodynamics. Major determinants of the pharmacogenomic
      outcome include pathogenic, mechanistic, metabolic, transporter and pleiotropic
      genes. The expression of these genes is under regulatory control of the
      epigenetic machinery. Approximately, 80% of the Caucasian population is deficient
      in the metabolization of drugs due to polymorphisms in metabolic genes;
      consequently, less than 40% of patients respond appropriately to conventional
      drugs. The implementation of pharmacogenomic procedures in the clinical practice
      may help to optimize therapeutics in NDDs.

PMID- 30236878
TI  - Hydromorphone protects CA1 neurons by activating mTOR pathway.
AB  - Hydromorphone has been shown to play protective effect in rat glial cell.
      However, whether hydromorphone plays important roles in ischemia-reperfusion (IR)
      injury and the involved signaling pathway remains unclear. In this study, we
      detected whether HM plays protective effect in IR injury mouse model, further
      followed by the mechanism exploration. Preconditioning with hydromorphone was
      performed for continuous 4 days at the doe of 2 mg/kg before IR injury induction.
      Intraperitoneal injection of rapamycin (Rapa) was administrated to examine the
      role of mTOR in IR injury. The mRNA expression level was detected by RT-PCR, and
      protein expression level was detected by western blot. Latency time and apoptosis
      of hippocampal CA1 neurons were detected 72 h after IR injury induction.
      Preconditioning with hydromorphone significantly increased Latency time,
      decreased apoptosis of hippocampal CA1 neurons and suppressed IR induced
      oxidative stress. Mechanically, preconditioning with hydromorphone increased Bcl
      2 and p-mTOR expression levels and decreased Bax expression levels. Rapa
      administration reverses the role of hydromorphone in protecting hippocampal CA1
      neurons from IR injury. Hydromorphone protect hippocampal CA1 neurons from IR
      injury via activating mTOR signaling pathway.

PMID- 30236880
TI  - Functional amyloidogenesis in immunocytes from the colonial ascidian Botryllus
      schlosseri: Evolutionary perspective.
AB  - Cytotoxic morula cells (MCs) and phagocytes are the circulating immunocytes of
      the colonial ascidian Botryllus schlosseri: Both these cells can synthesise
      amyloid fibrils, supporting the idea that physiological amyloidogenesis is
      involved in inflammation and modulation of immune responses. Intriguingly,
      amyloid of B. schlosseri immunocytes is made of two different proteins. MCs, the
      first cells to sense non-self and involved in the allorejection reaction between
      contacting genetically incompatible colonies, use melanin encapsulation as the
      principal method to fight non-self. They release amyloid fibrils formed by p102
      protein that allow the packaging and deposit of melanin and other toxic molecules
      nearby the invader or in the contact region of incompatible colonies. Phagocytes
      release amyloid-based extracellular traps when challenged with microbes: their
      amyloid fibrils harbour BsAPP, an orthologue of the vertebrate amyloidogeneic
      protein APP. This strategy of immune response, present also in human neutrophils,
      allows phagocytes to block and engulf bacteria and fungi.

PMID- 30236879
TI  - Shark IgNAR-derived binding domains as potential diagnostic and therapeutic
      agents.
AB  - Many of the most successful drugs generated in recent years are based upon
      monoclonal antibodies (mAbs). However, for some therapeutic and diagnostic
      applications mAbs are far from ideal; for example, while their relatively large
      size and inherent receptor binding aids their longevity in vivo it can also limit
      their tissue penetration. Further, their structural complexity makes them
      expensive to produce and prone to denaturation in non-physiological environments.
      Thus, researchers have been searching for alternative antigen-binding molecules
      that can be utilized in situations where mAbs are suboptimal tools. One potential
      source currently being explored are the shark-derived binding domains known as
      VNARs. Despite their small size VNARs can bind antigens with high specificity and
      high affinity. Combined with their propensity to bind epitopes that are
      inaccessible to conventional mAbs, and their ability to resist denaturation,
      VNARs are an emerging prospect for use in therapeutic, diagnostic, and
      biotechnological applications.

PMID- 30236881
TI  - Litopenaeus vannamei heat shock protein 70 (LvHSP70) enhances resistance to a
      strain of Vibrio parahaemolyticus, which can cause acute hepatopancreatic
      necrosis disease (AHPND), by activating shrimp immunity.
AB  - Heat shock protein 70 (HSP70) acts as a molecular chaperone and a stress protein,
      but also plays important roles in innate and adaptive immune responses. Previous
      studies have reported that non-lethal heat shock (NLHS) could enhance the
      resistance of Pacific white shrimp Litopenaeus vannamei to a specific strain of
      Vibrio parahaemolyticus, which carried a toxin-producing plasmid (VPAHPND), via
      the induction of LvHSP70 transcription. Here, we further investigated the
      specific function of LvHSP70 in shrimp immunity. The upregulation of LvHSP70 at
      the protein level was detected during recovery time after NLHS treatment, using
      both western blot analysis and immunofluorescence microscopy. We found that NLHS
      immediately activated the production of LvHSP70 in shrimp hemocytes and that such
      induction was observed in all three types of hemocytes: hyaline; granular and
      semi-granular cells. Furthermore, the role of LvHSP70 in bacterial defense was
      investigated using the heterologous expression of recombinant LvHSP70 (rLvHSP70)
      in Escherichia coli. Shrimp receiving rLvHSP70 by injection showed an increased
      survival rate (75%) to VPAHPND infection compared to just 20% survival in the
      control group injected with bovine serum albumin (BSA). We also demonstrated that
      the injected rLvHSP70 accumulated in shrimp hemocytes and was detected in the
      intracellular space of hemocyte cells leading to the induced expression (P<0.05)
      of several immune-related genes (LvMyD88, LvIKKbeta, LvIKKepsilon, LvCrustin I,
      LvPEN2, LvPEN3, LvproPO1, LvproPO2 and LvTG1). Collectively, these results
      suggest that LvHSP70 plays a crucial role in bacterial defense by activating the
      shrimp immune system.

PMID- 30236882
TI  - Outsourcing natural resource requirements within China.
AB  - Consumption demands are final drivers for the extraction and allocation of
      natural resources. This paper investigates demand-driven natural resource
      requirements and spatial outsourcing within China in 2012 by using the latest
      multi-regional input-output model. Exergy is adopted as a common metric for
      natural resources input. The total domestic resource exergy requirements amounted
      to 125.5 EJ, of which the eastern area contributed the largest share of 44.5%,
      followed by the western area (23.9%), the central area (23.0%) and the
      northeastern area (8.6%). Investment was the leading final demand category,
      accounting for 52.9% (66.4 EJ) of national total embodied resource use (ERU). The
      total trade volumes of embodied resource were equivalent to 69.6% of the total
      direct resource input (DRI), mostly transferred from the central and western
      regions such as Inner Mongolia, Shanxi, Shaanxi and Xinjiang to the eastern
      regions such as Jiangsu, Zhejiang, Guangdong and Shanghai. The northeastern and
      eastern areas had physical net imports of 1213.5 PJ and 38452.6 PJ, while the
      central and western inland areas had physical net exports of 6364.5 PJ and
      33301.5 PJ, respectively. Shanghai, Beijing, Zhejiang, Jiangsu and Guangdong had
      prominent ERUs which respectively were 101.6, 12.6, 11.7, 8.4 and 4.3 times of
      their DRIs. The ERUs of Inner Mongolia, Shaanxi, Shanxi, Ningxia and Guizhou were
      equal to only 17.6%, 25.3%, 27.9%, 46.0% and 50.2% of their DRIs, respectively.
      Regional uneven development resulted in imbalanced resource requirements across
      China. The findings can provide a deep understanding of China's resource-driven
      economic development mode, and contribute to reducing regional resource
      footprints and their environment outcomes under the "new normal economy".

PMID- 30236883
TI  - Analysis of pelletizing from corn cob waste.
AB  - In recent years, biomass market has constantly increased. Pellet industry has
      started looking for new products with the potential to be used as biofuels. Among
      them are agricultural wastes, such as corn cob waste, which presents some
      characteristics that make its direct use in industrial facilities possible.
      However, these properties are not enough for its use in domestic stoves and
      boilers, where higher quality of fuel is needed. For this reason, densification
      is used. In the present research work a technical and energy analysis of corn cob
      waste pelletizing was carried out in a semi-industrial pelletizer. Some
      relationships between variables, such as moisture, bulk density and mechanical
      durability, were analyzed, as well as their influence on energy use and final
      productivity. The results were satisfactory, as the pellets manufactured
      fulfilled with most specifications that were consulted, with higher values than
      those recorded for similar kinds of pellets. Concerning the energy study, the
      increase in production justified a higher energy consumption of the process in
      order to get a higher productivity ratio.

PMID- 30236884
TI  - The study on pyrolysis of oil-based drilling cuttings by microwave and electric
      heating.
AB  - In this paper, the following questions were investigated: the proportion of mass
      loss, the mass fraction of oil, the structure, composition and ultimate analysis
      of solid residues and gas products. By comparing the treatment effect of using
      both microwave and electric as the source of heat to dispose the oil-based
      drilling cuttings (OBDC), the advantages of microwave heating treatment were
      demonstrated. Meanwhile, the composition of liquid products by microwave
      pyrolysis was analyzed. The results show that the microwave heating is better
      than electric heating and the former can promote the pyrolysis of petroleum
      hydrocarbons. The results of component analysis of the liquid products from OBDC
      by microwave pyrolysis show that C12~C20 components pyrolyze at 500  degrees C.
      At the same time, a mass of C21~C24 components volatilize. At the temperature
      above 500  degrees C, the thermal cracking reactions of >C25 components occur and
      a maximum content of paraffin in liquid products is obtained. As the temperature
      increases, the components obtained by pyrolysis become more and more complex.

PMID- 30236885
TI  - Translating Ecological Integrity terms into operational language to inform
      societies.
AB  - It is crucial that societies are informed on the risks of impoverished ecosystem
      health for their well-being. For this purpose, Ecological Integrity (EI) is a
      useful concept that seeks to capture the complex nature of ecosystems and their
      interaction with social welfare. But the challenge remains to measure EI and
      translate scientific terminology into operational language to inform society. We
      propose an approach that simplifies marine ecosystem complexity by applying
      scientific knowledge to identify which components reflect the state or state
      change of ecosystems. It follows a bottom-up structure that identifies, based on
      expert knowledge, biological components related with past and present changing
      conditions. It is structured in 5 stages that interact in an adaptive way: stage
      1, in situ observations suggest changes could be happening; stage 2 explores
      available data that represent EI; stage 3, experts' workshops target the
      identification of the minimum set of variables needed to define EI, or the risk
      of losing EI; an optative stage 4, where deviance from EI, or risk of deviance,
      is statistically assessed; stage 5, findings are communicated to society. We
      demonstrate the framework effectiveness in three case studies, including a data
      poor situation, an area where lack of reference sites hampers the identification
      of historical changes, and an area where diffuse sources of stress make it
      difficult to identify simple relationships with of ecological responses. The
      future challenge is to operationalise the approach and trigger desirable society
      actions to strengthen a social-nature link.

PMID- 30236886
TI  - Millepora species (Fire Coral) Sting: A Case Report and Review of Recommended
      Management.
AB  - Fire corals (Millepora spp) are the second most common reef-forming organisms and
      are frequently found in tropical and subtropical waters. Fire corals are not true
      corals but rather hydrozoans more closely related to jellyfish and sea nettles.
      Rigidly affixed to the reef and with a branching structure, each fire coral is a
      colony of numerous individual hydrozoans forming a collective symbiotic organism.
      It is common for divers to accidentally make contact with fire corals. Fire coral
      contact is characterized by the immediate onset of burning pain caused by venom
      discharge from numerous tiny nematocysts located externally on the creature.
      Treatment consists of saltwater irrigation of the wound, nematocyst removal, and
      supportive care of the associated symptoms of pain, dermatitis, and pruritus.
      Rarely, fire coral can cause systemic toxicity. We present a case report of a 30
      y-old recreational diver who experienced a fire coral sting of her left anterior
      thigh and review the recommended prevention and management of fire coral stings.

PMID- 30236887
TI  - Summation of peaks and L34 ribosomal protein in the presence and absence of
      antibiotics enables susceptibility testing using MALDI-TOF mass spectrometry in
      2h from Escherichia coli-positive blood cultures.
AB  - INTRODUCTION: We have developed a MALDI-TOF-mediated phenotypic method, which
      determines antibiotic susceptibility (AS) from positive blood cultures (BCs) in
      2h. We developed a software for process automation. We report results on
      Escherichia coli-positive BCs with cefotaxime (CTX) and ciprofloxacin (CIP).
      METHODS: We studied CIP and CTX activity in 18 and 17 real E. coli-positive BCs,
      and in 56 and 45 spiked BCs, respectively. Positive BCs were incubated for 2h
      without any antibiotics, and with 2mg/l and 4mg/l of CIP and CTX. The extraction
      was performed using ethanol/formic acid. Spectra were processed with specifically
      developed software which compares the peaks' intensity and the size of specific
      peaks. RESULTS: The set cut-off point was a 3-fold decrease in the summation of
      all peaks and/or the 5382m/z peak value (ribosomal protein L34). In simulated
      BCs, the correlation of CIP 2mg/l and 4mg/l with Etest(r) was 94.6% and 98.2%,
      respectively; for CTX 2mg/l and 4mg/l, this correlation was 95.6%. In real BCs,
      the correlations were 100% for CIP (2mg/l and 4mg/l) and 88.2% and 94.1% for CTX
      2mg/l and 4mg/l, respectively. Resistant isolates were always correctly
      classified. CONCLUSION: This method provides accurate, fast and inexpensive AS
      information. The method can be automated, making it easier to implement in a
      microbiology laboratory routine.

PMID- 30236888
TI  - Traveller's diarrhoea by Vibrio cholerae in patients returning from the Dominican
      Republic.

PMID- 30236889
TI  - Adapting the chemical unfolding assay for high-throughput protein screening using
      experimental and spectroscopic corrections.
AB  - The chemical unfolding (denaturation) assay can be used to calculate the change
      in the Gibbs free energy of unfolding, DeltaG, and inflection point of unfolding,
      to collectively inform on molecule stability. Here, we evaluated methods for
      calculating the DeltaG across 23 monoclonal antibody sequence variants. These
      methods are based on how the measured output (intrinsic fluorescence intensity)
      is treated, including utilizing (a) a single wavelength, (b) a ratio of two
      wavelengths, (c) a ratio of a single wavelength to an area, and (d) a scatter
      correction plus a ratio of a single wavelength to an area. When applied to the
      variants, the three ratio methods showed comparable results, with a similar
      pooled standard deviation for the DeltaG calculation, while the single-wavelength
      method is shown as inadequate for the data in this study. However, when light
      scattering is introduced to simulated data, only the scatter-correction area
      normalization method proves robust. Using this method, common plate-based
      spectrophotometers found in many laboratories can be used for high-throughput
      screening of mAb variants and formulation stability studies.

PMID- 30236890
TI  - Microfluidics for cell factory and bioprocess development.
AB  - Bioindustry is expanding to an increasing variety of food, chemical and
      pharmaceutical products, each requiring rapid development of a dedicated cell
      factory and bioprocess. Microfluidic tools are, together with tools from
      synthetic biology and metabolic modeling, being employed in cell factory and
      bioprocess development to speed up development and address new products. Recent
      examples of microfluidics for bioprocess development range from integrated
      devices for DNA assembly and transformation, to high throughput screening of cell
      factory libraries, and micron scale bioreactors for process optimization. These
      improvements act to improve the biotechnological engineering cycle with tools for
      building, testing and evaluating cell factories and bioprocesses by increasing
      throughput, parallelization and automation.

PMID- 30236891
TI  - Association between alcohol intake and incident hypertension in the Korean
      population.
AB  - BACKGROUND AND AIMS: Alcohol consumption is generally associated with increased
      risk of hypertension. However, the effect of alcohol intake on the incidence of
      hypertension remains controversial due to inconsistent results across studies. We
      investigated the association between alcohol intake and hypertension in a Korean
      population. METHODS AND RESULTS: The two studies that we evaluated herein, the
      CAVAS study (N = 6,259) and the Ansan-Ansung study (N = 2,461), were part of the
      Korean Genome and Epidemiology study on participants aged between 40 and 69 years
      who underwent community-based health checkups (2 years for the CAVAS study follow
      up and 12 years for the Ansan-Ansung study follow-up). We categorized the
      participants into four groups based on baseline and follow-up period
      measurements. We found that baseline alcohol consumption increased the risk of
      incident hypertension in the CAVAS study [HR (95% CI), low: 1.094 (0.848-1.411),
      intermediate: 1.661 (1.227-2.141), high: 1.723 (1.274-2.330)]. Intermediate and
      high alcohol consumption were associated with increased risk of incident
      hypertension in men [2.086 (1.438-3.027) for intermediate, and 1.952 (1.294
      2.944) for high], but women only had increased risk of incident hypertension with
      high consumption [1.950 (1.100-3.455)]. In addition, we found a positive
      association between the alcohol consumption pattern (over 10 years) and the risk
      of incident hypertension in the Ansan-Ansung study [HR (95% CI), light: 1.316
      (1.126-1.539), moderate: 1.445 (1.193-1.750), heavy: 1.897 (1.488-2.419)].
      Moderate and heavy consumption patterns carried higher risks of incident
      hypertension compared with never-drinking in men [moderate: 1.292 (1.033-1.617),
      heavy: 1.703 (1.293-2.242)], but women with light consumption patterns were at
      increased risk of incident hypertension [1.572 (1.302-1.899)]. CONCLUSIONS: This
      large prospective cohort study revealed a linear association between baseline
      alcohol consumption, subsequent alcohol consumption patterns (over more than 10
      years), and hypertension risk in the Korean population.

PMID- 30236893
TI  - Surfactant for the management of pediatric hydrocarbon ingestion.

PMID- 30236892
TI  - CXCR2-Expressing Tumor Cells Drive Vascular Mimicry in Antiangiogenic Therapy
      Resistant Glioblastoma.
AB  - BACKGROUND: Glioblastoma (GBM) was shown to relapse faster and displayed
      therapeutic resistance to antiangiogenic therapies (AATs) through an alternative
      tumor cell-driven mechanism of neovascularization called vascular mimicry (VM).
      We identified highly upregulated interleukin 8 (IL-8)-CXCR2 axis in tumor cells
      in high-grade human glioma and AAT-treated orthotopic GBM tumors. METHODS: Human
      GBM tissue sections and tissue array were used to ascertain the clinical
      relevance of CXCR2-positive tumor cells in the formation of VM. We utilized U251
      and U87 human tumor cells to understand VM in an orthotopic GBM model and AAT
      mediated enhancement in VM was modeled using vatalanib (anti-VEGFR2) and avastin
      (anti-VEGF). Later, VM was inhibited by SB225002 (CXCR2 inhibitor) in a
      preclinical study. RESULTS: Overexpression of IL8 and CXCR2 in human datasets and
      histological analysis was identified as a bonafide candidate to validate VM
      through in vitro and animal model studies. AAT-treated tumors displayed a higher
      number of CXCR2-positive GBM-stem cells with endothelial-like phenotypes. Stable
      knockdown of CXCR2 expression in tumor cells led to decreased tumor growth as
      well as incomplete VM structures in the animal models. Similar data were obtained
      following SB225002 treatment. CONCLUSIONS: The present study suggests that tumor
      cell autonomous IL-8-CXCR2 pathway is instrumental in AAT-mediated resistance and
      VM formation in GBM. Therefore, CXCR2 can be targeted through SB225002 and can be
      combined with standard therapies to improve the therapeutic outcomes in clinical
      trials.

PMID- 30236894
TI  - The effects of skin pigmentation on the detection of genital injury from sexual
      assault.

PMID- 30236895
TI  - The evaluation and management of decompensated hypertrophic cardiomyopathy in the
      emergency department.

PMID- 30236896
TI  - Characteristics of dual drug benefit use among veterans with dementia enrolled in
      the Veterans Health Administration and Medicare Part D.
AB  - BACKGROUND: Obtaining prescription medications from multiple health systems may
      complicate coordination of care. Older Veterans who obtain medications
      concurrently through Veterans Affairs (VA) benefits and Medicare Part D benefits
      (dual users) are at higher risk of unintended negative outcomes. OBJECTIVE: To
      explore characteristics predicting dual drug benefit use from both VA and
      Medicare Part D in a national sample of older Veterans with dementia. METHODS:
      Administrative data were obtained from the VA and Medicare for a national sample
      of 110,828 Veterans with dementia ages 68 and older in 2010. Veterans were
      classified into three drug benefit user groups based on the source of all
      prescription medications they obtained in 2010: VA-only, Part D-only, and Dual
      Use. Multinomial logistic regression was used to examine predictors of drug
      benefit user group. The source of prescriptions was described for each of the ten
      most frequently used drug classes and opioids. RESULTS: Fifty-six percent of
      Veterans received all of their prescription medications from VA-only, 28% from
      Part D-only, and 16% from both VA and Part D. Veterans who were eligible for
      Medicaid or who had a priority group score conferring less generous drug benefits
      within the VA were more likely to be Part D-only or dual users. Nearly one fourth
      of Veterans taking opioids concurrently received opioid prescriptions from dual
      sources (24.7%). CONCLUSIONS: Medicaid eligibility and Veteran priority group
      status, which largely decrease copayments for drugs obtained outside versus
      within the VA, respectively, were the main factors predicting drug user benefit
      group. Policies to encourage single-system prescribing and enhance communication
      across health systems are crucial to preventing negative health outcomes related
      to care fragmentation.

PMID- 30236897
TI  - Efficiency evaluation of the process control virus "Mengovirus" in real time RT
      PCR viral detection in the bivalve mollusc Donax sp.
AB  - There are many problems associated with extracting viral genetic material from
      contaminated samples of bivalve molluscs, specifically because the hepatopancreas
      has many PCR inhibitors. For this reason, nucleic acid extraction methods must
      consider a process control virus (PCV) that may help to measure extraction
      efficiency. In the market, there are many commercial kits to extract nucleic acid
      from RNA viruses, as well as others to perform one-step real time RT-PCR, but
      most of them have not been evaluated for bivalve molluscs. For this reason, the
      aim of this study was to evaluate the extraction efficiency of the PCV
      (Mengovirus), it was performed using 3 different RNA extraction kits and 2 one
      step real time RT-PCR kits. 10 MUL of Mengovirus at a concentration of 1.6 * 104
      viral particles/MUL was added to 29 samples of hepatopancreas of Donax sp. Sample
      processing was performed according to the ISO/TS 15216-2: 2013 standard. RNA was
      extracted from each sample with the kits: (1) BioMerieux NucliSens(r)system
      (BioMerieux SA, France), (2) PureLinkTM RNA Mini Kit (Ambion-Life TechnologiesTM,
      USA) and (3) Hugh Pure RNA Tissue Kit (Roche SA, Germany). Once RNA was
      extracted, one-step real time RT-PCR was conducted by using the following kits:
      (A) Ultrasense One-step qRT-PCR Kit (Invitrogen, USA) according to ISO/TS 15216
      2:2013, and (B) Mengovirus@ceeramToolsTM Kit (Ceeram, France) according to the
      manufacturer's specifications. The extraction efficiency of PCV when using the
      extraction kits 1, 2 and 3 combined with real time RT-PCR kit A were: 10.82, 1.90
      and 0.64, respectively; and when using real time RT-PCR kit B were: 7.34, 0.97
      and 0.47, respectively. It is concluded that the BioMerieux NucliSens(r)system
      RNA extraction kit was the most efficient and that the Ultrasense One-step qRT
      PCR Kit performed better than the Mengovirus@ceeramToolsTM RT-PCR kit.

PMID- 30236898
TI  - Streamlined generation of plant virus infectious clones using the pLX mini binary
      vectors.
AB  - Recent metagenomic surveys have provided unprecedented amounts of data that have
      revolutionized our understanding of virus evolution and diversity. Infectious
      clones are powerful tools to aid the biological characterization of viruses. We
      recently described the pLX vectors, a set of mini binary T-DNA vectors (~3 kb)
      that includes strong bacterial terminators and a minimal replicon from the broad
      host-range plasmid pBBR1, which replicate autonomously in both Escherichia coli
      and Agrobacterium. In this study, a workflow that encompassed pLX binary vectors,
      overlap-based assembly strategies, and sequencing-by-synthesis verification steps
      is described and applied for the streamlined generation of infectious clones
      suitable for Agrobacterium-mediated delivery. The pLX-based vectors herein
      assembled include the first infectious clone of Wasabi mottle virus, a crucifer
      infecting tobamovirus, as well as binary vectors of positive-single-stranded RNA
      and single- and double-stranded DNA viruses from the Potyviridae, Geminiviridae
      and Caulimoviridae families, respectively. Finally, the clones generated were
      used to agro-inoculate the model plant Arabidopsis thaliana and infections were
      confirmed by a multiplex RT-PCR assay. This workflow facilitated the rapid
      generation of infectious clones which, together with agro-infection scalability,
      would allow the pursuit of systematic insights into virus biology and physiology
      of plant infections and the design of novel biotechnological applications.

PMID- 30236899
TI  - Laparoscopic Dissection of the Pelvic Ureter: Rules of Engagement.
AB  - STUDY OBJECTIVE: To point out the relevant anatomy of the ureter and to
      demonstrate its rules of dissection. DESIGN: An educational video to explain how
      to use ureteral relevant anatomy and the principle of dissection to perform safe
      ureterolysis during laparoscopic procedures. SETTING: A tertiary care university
      hospital and endometriosis referential center. INTERVENTIONS: Anatomic keynotes
      of the ureter and examples of ureterolysis. CONCLUSION: This video shows the
      feasibility of laparoscopic ureteral dissection and provides safety rules to
      perform ureterolysis. Identification and dissection of the ureter should be part
      of all gynecologic surgeons' background to reduce the risk of complications [1].
      Knowledge of anatomy plays a pivotal role, allowing the surgeon to keep the
      ureter at a distance and minimizing the need for ureterolysis. Unfortunately, the
      need for ureteral dissection is not always predictable preoperatively, and
      gynecologic surgeons need to master this technique, especially when approaching
      more complex procedures such as endometriosis [2]. An implicit risk of damage
      cannot be denied when performing ureterolysis; therefore, the ureter should be
      dissected only when strictly necessary and handled with care to minimize the use
      of energy [3].

PMID- 30236900
TI  - Perspectives on the opioid crisis from pain medicine clinicians.
AB  - Patients experiencing a terminal drug related event reflect a sentinel event. If
      this pharmacotherapy is a widely used agent, it may be viewed as a catastrophic
      problem. If patients are dying from illegal drug use when the medical
      establishment fails them by withdrawing or minimizing their medically prescribed
      medication, then the burden rests with their health care providers, legislation,
      and insurance carriers to actively participate in a collegial fashion to achieve
      parity. Causing a decay in functionality in previously functional patients, may
      occur with appropriately prescribed opioid medications addressing non-cancer pain
      when withdrawing or diminishing either with or without patient consent. The
      members of the medical profession have diminished their prescribing of opioids
      for their patients out of apparent fear of reprisal, state or federal government
      sanctions, and other concerned groups. Diminishing former dosages or deleting the
      opioid medication, preferably in concert with the patient, often results in
      inequitable patient care. Enforcing sanctioned decreases or ceasing to prescribe
      from their former required/established opioid medications precipitate patient
      discord. In absence of opioid misuse, abuse, diversion or addiction based upon
      medical "guidelines" and with a poor foundation of Evidence Based Medicine the
      CDC guidelines, it may be masked as a true guideline reflecting a decrement of
      clinical judgment, wisdom, and compassion. This article also discusses the role
      of pharmacy chains, insurance carriers, and their pharmacy benefit managers
      (PBMs) contribution to this multidimensional problem. There may be a potential
      solution, identified in this paper, if all the associated political, medical and
      insurance groups work cohesively to improve patient care. This article and the
      CDC guidelines are not focused at hospice, palliative, end of life care pain
      management.

PMID- 30236901
TI  - Associations of Age and Gender with Negative Symptom Factors and Functioning
      Among Middle-Aged and Older Adults with Schizophrenia.
AB  - OBJECTIVE: Gender differences in neurocognition, social skills, and negative
      symptoms, favoring women, have been documented among young/middle-aged adults
      with schizophrenia. However, gender differences have rarely been examined among
      older adults with schizophrenia, when decreases in circulating estrogens may
      impact outcomes among women. METHODS: Community-dwelling adults (N = 242, ages 40
      85) with schizophrenia/schizoaffective disorder completed assessments of negative
      symptoms (expressive and experiential deficits), neurocognition, and social
      skills. Mann-Whitney U tests examined gender differences; a regression-based
      bootstrapped approach to moderation examined gender by age interactions. RESULTS:
      Female participants had better neurocognition (U = 6,814.00, p = 0.011) and less
      severe experiential deficits (U = 4,130.50, p = 0.022). There was no gender
      difference in social skills (U = 5,920.50, p = 0.150). Older age was associated
      with greater expressive deficits among men but not women (b = -0.04; 95%
      confidence interval -0.0780, -0.0114; bootstrap p = 0.009). CONCLUSION: Gender
      differences among adults with schizophrenia may vary depending on age; gender
      differences in negative symptoms may vary by symptom subgroup.

PMID- 30236902
TI  - Low Tri-iodothyronine Syndrome Is Associated With Cognitive Impairment in
      Patients With Acute Ischemic Stroke: A Prospective Cohort Study.
AB  - OBJECTIVE: Low tri-iodothyronine (T3) syndrome is a predictor of poor prognosis
      in patients with stroke. Poststroke cognitive impairment (PSCI) is a common and
      important complication after stroke. The association between low T3 syndrome and
      PSCI is unclear. We aimed to explore the potential relationship between low T3
      syndrome and PSCI in the acute phase of ischemic stroke at a 1-month follow-up
      visit. METHODS: In total, 314 ischemic stroke patients were consecutively
      enrolled in the study and followed up at 1 month. Thyroid hormones were measured
      within 24 hours after admission. Cognitive function was evaluated by the Mini
      Mental State Exam (MMSE) 1 month after acute ischemic stroke. Cognitive
      impairment was defined as an MMSE score of less than 27. Cognitive impairment
      severity was categorized as severe, mild, or none (MMSE score <23, 23-26, or
      >=27, respectively). RESULTS: According to the MMSE score, 182 participants
      (58.0%) had cognitive impairment 1 month after stroke. Patients with low T3
      syndrome were more prone to have cognitive impairment than patients with normal
      levels of T3 (p < 0.001). After adjusting for potential confounders in our
      logistic model, low T3 syndrome was independently associated with PSCI (odds
      ratio 4.319, 95% confidence interval 1.553-12.013, p = 0.005). CONCLUSION: Low T3
      syndrome in the acute phase of ischemic stroke was associated with a higher
      prevalence of 1-month PSCI, independently of established risk factors.

PMID- 30236903
TI  - Home-based biofeedback for dyssynergic defecation.

PMID- 30236905
TI  - Biotechnological Advances in Bacterial Microcompartment Technology.
AB  - Bacterial microcompartments (BMCs) represent proteinaceous macromolecular
      nanobioreactors that are found in a broad range of bacteria, and which are
      associated with either anabolic or catabolic processes. They consist of a
      semipermeable outer shell that packages a central metabolic enzyme or pathway,
      providing both enhanced flux and protection against toxic intermediates.
      Recombinant production of BMCs has led to their repurposing with the
      incorporation of altogether new pathways. Deconstructing BMCs into their
      component parts has shown that some individual shell proteins self-associate into
      filaments that can be further modified into a cytoplasmic scaffold, or
      cytoscaffold, to which enzymes/proteins can be targeted. BMCs therefore represent
      a modular system that is highly suited for engineering biological systems for
      useful purposes.

PMID- 30236904
TI  - Home-based versus office-based biofeedback therapy for constipation with
      dyssynergic defecation: a randomised controlled trial.
AB  - BACKGROUND: Office-based biofeedback therapy is effective for constipation with
      dyssynergic defecation, but must be performed by skilled staff, is only available
      in selected centres, and requires multiple visits. The efficacy of home-based
      biofeedback therapy is unknown. We compared clinical and subjective outcomes with
      home-based and office-based approaches. METHODS: In this randomised controlled
      trial, eligible patients were adult outpatients (age 18-80 years) who met the
      Rome III criteria for functional constipation and who had been referred to a
      tertiary-care centre after non-response to routine management, and who had
      dyssynergic defecation. Patients were randomly assigned according to a schedule
      generated in advance by the study biostatistician, in permuted blocks of four, to
      receive office-based or home-based biofeedback therapy. Office-based biofeedback
      comprised therapist-guided pelvic floor training for six sessions over 3 months
      (visits every 2 weeks). Home-based biofeedback comprised 20 min self-training
      sessions twice per day, in which a self-inserted probe was used to provide visual
      feedback via a handheld monitoring device of anal sphincter pressure and push
      effort. Patients recorded in diaries the time of each defecation attempt, stool
      consistency, straining effort, feeling of incomplete evacuation, need for digital
      assistance with stooling, and satisfaction with bowel function, from 1 week
      before enrolment to the end of follow-up. Treatment responders were defined post
      hoc as those with normalisation of dyssynergic defecation and an increase in the
      number of complete spontaneous bowel movements per week by 3 months. Cost
      outcomes calculated from health-care costs and loss of salary were assessed from
      hospital billing and medical records and questionnaires. Primary outcome measures
      were the presence of a dyssynergic pattern during attempted defecation, balloon
      expulsion time, the number of complete spontaneous bowel movements per week, and
      satisfaction with bowel function, assessed by intention to treat (non
      inferiority) and per protocol. This trial is registered with ClinicalTrials.gov,
      number NCT03202771. FINDINGS: Of 300 patients screened we enrolled 100, from Jan
      7, 2005, to Jan 31, 2010. 83 patients completed training (38 [76%] of 50 in the
      home-based biofeedback group and 45 [90%] of 50 in the office-based biofeedback
      group). 34 (68%) patients in the home-based group and 35 (70%) in the office
      based group were classified as responders. All primary outcomes improved
      significantly from baseline in the two treatment groups (all p<0.0001). Home
      based biofeedback therapy was non-inferior to office-based therapy for number of
      complete spontaneous bowel movements per week, satisfaction with bowel function,
      and balloon expulsion time in the intention-to-treat and per-protocol analyses,
      and for dyssynergia in the per-protocol analysis. No adverse events were
      reported. The median cost of home-based biofeedback therapy was significantly
      lower than that for office-based treatment (US$1081.70, IQR 794.90-1399.30 vs
      $1942.50, 1621.70-2369.00, p=0.009). INTERPRETATION: Home-based and office-based
      biofeedback therapy for dyssynergic defecation improved bowel symptoms and
      physiology with similar efficacy. A home-based programme could substantially
      broaden the availability and use of this treatment. FUNDING: National Institutes
      of Health.

PMID- 30236906
TI  - Thermal decomposition kinetics of guarana seed residue through thermogravimetric
      analysis under inert and oxidizing atmospheres.
AB  - This work aims to analyze the thermal decomposition kinetics of guarana seed
      residue applying inert and oxidizing atmospheres. Thermal decomposition
      experiments were carried out in a thermogravimetric analyser using heating rates
      of 5, 10 and 15  degrees C/min. Three thermal decomposition stages were
      identified: dehydration; pyrolysis/oxidative pyrolysis, and
      carbonization/combustion, respectively. In order to obtain the estimation of the
      activation energies, the isoconversional method proposed by Vyazovkin (1997) was
      applied. Besides that, three and six independent parallel reactions schemes were
      applied for respective atmospheres. The ranges of activation energy were of 52
      140 kJ/mol and 71-171 kJ/mol for inert and oxidizing atmosphere, respectively.
      The modeling of conversion rates presented a good agreement in relation to the
      experimental data (AD < 4%).

PMID- 30236907
TI  - Enrichment and characterization of an environmental microbial consortium
      displaying efficient keratinolytic activity.
AB  - Keratin refers to a group of insoluble and recalcitrant protein materials.
      Slaughterhouses produce large amount of keratinous byproducts, which are either
      disposed or poorly valorized through costly thermochemical processes for animal
      feed formulation. Learning from nature, keratinolytic microbial consortia stand
      as a cost-efficient and environmental friendly way to valorize this recalcitrant
      resource. Directed selection was applied to enrich soil-born microbial consortia,
      using sequential batch cultivations in keratin medium, while measuring enzymes
      activity and monitoring consortia compositions via 16S rRNA gene amplicon
      sequencing. A promising microbial consortium KMCG6, featuring mainly members of
      Bacteroidetes and Proteobacteria, was obtained. It possessed keratinolytic
      activity with <25% residual substrate remaining, which also displayed a high
      degradation reproducibility level after long-term cryopreservation. This work
      represents an advance in the field of alpha-keratin degradation with potential
      for practical applications.

PMID- 30236908
TI  - Skin dose estimation using virtual structures for Contura Multi-Lumen Balloon
      breast brachytherapy.
AB  - PURPOSE: To propose a workflow that uses ultrasound (US)-measured skin-balloon
      distances and virtual structure creations in the treatment planning system to
      evaluate the maximum skin dose for patients treated with Contura Multi-Lumen
      Balloon applicators. METHODS AND MATERIALS: Twenty-three patients were analyzed
      in this study. CT and US were used to investigate the interfractional skin
      balloon distance variations. Virtual structures were created on the planning CT
      to predict the maximum skin doses. Fitted curves and its equation can be obtained
      from the skin-balloon distance vs. maximum skin dose plot using virtual structure
      information. The fidelity of US-measured skin distance and the skin dose
      prediction using virtual structures were assessed. RESULTS: The differences
      between CT- and US-measured skin-balloon distances values had an average of -0.5
      +/- 1.1 mm (95% confidence interval [CI] = -1.0 to 0.1 mm). Using virtual
      structure created on CT, the average difference between the predicted and the
      actual dose overlay maximum skin dose was -1.7% (95% CI = -3.0 to -0.4%).
      Furthermore, when applying the US-measured skin distance values in the virtual
      structure trendline equation, the differences between predicted and actual
      maximum skin dose had an average of 0.7 +/- 6.4% (95% CI = -2.3% to 3.7%).
      CONCLUSIONS: It is possible to use US to observe interfraction skin-balloon
      distance variation to replace CT acquisition. With the proposed workflow, based
      on the creation of virtual structures defined on the planning CT- and US-measured
      skin-balloon distances, the maximum skin doses can be reasonably estimated.

PMID- 30236909
TI  - Population specificity of sex estimation from vertebrae.
AB  - Vertebral measurements have been shown to provide accurate classification of sex.
      However, the use of vertebral discriminant functions (DFs) in forensic
      anthropology and bioarchaeology is limited due to the unknown degree of their
      population specificity. Additionally, the performance of vertebral DFs has not
      yet been assessed at higher posterior probability thresholds. In this study, we
      tested the performance of previously published DFs for sex classification from
      Th12 and L1 vertebrae within a range of 0.5-0.95 posterior probabilities in a
      model of geographically distant population based on an autopsy Central European
      (CE) sample (Czech Republic; n=72) from the 1930s. Further, we derived new pooled
      DFs from a sample representing ecogeographically diverse populations, new DFs
      derived from the autopsy CE sample, and new Medieval CE DFs derived from the
      Pohansko sample (n=129) and evaluated their performance at our testing autopsy CE
      sample. Most vertebral measurements showed population specificity in sex
      assessment. However, we identified two Th12 measurements (anteroposterior body
      diameter and mediolateral body diameter) usable for sex estimation across
      populations. We showed that the accuracy of vertebral DFs can be increased to 95%
      of correctly classified individuals in up to 64% of the studied sample by setting
      a higher posterior probability threshold. Finally, we showed that even the DFs
      derived from relatively small subsamples (30% of the population size) can provide
      accurate sex classification. This finding highlights the applicability of the
      hybrid approach in sex classification from vertebrae. To facilitate sex
      classification from vertebrae, we provide a software tool for sex classification
      from any vertebral measurement and reference samples tested in this study
      including the previously published DFs.

PMID- 30236910
TI  - Molecular characterization and gene expression of syntaxin-1 and VAMP2 in the
      olfactory organ and brain during both seaward and homeward migrations of chum
      salmon, Oncorhynchus keta.
AB  - Anadromous Pacific salmon (Genus Oncorhynchus) imprint odorants from their natal
      streams during their seaward migration, and adult salmon use olfaction to
      identify their natal streams during their homeward migration. However, little is
      known about the molecular mechanisms of olfactory imprinting in the salmon
      nervous system. Our previous study suggested that the snap25s gene (encoding a
      soluble N-ethylmaleimide-sensitive factor attachment protein receptor [SNARE]
      protein) is involved in pre-synaptic functions for olfactory imprinting and/or
      olfactory memory retrieval in chum salmon (O. keta). In this study, the
      expression of other SNARE proteins was analyzed in chum salmon brains. Three
      cDNAs, encoding salmon SNARE proteins (STX-1a, STX-1b, and VAMP2), were isolated
      and sequenced, which are well-conserved among vertebrates. Quantitative PCR
      detected the expression of stx1s and vamp2 in all regions of the brain, and
      especially highly in the olfactory bulb (OB) and telencephalon. The expression
      levels of snares in the olfactory rosette (OR) were higher during seaward
      migration than in adult life stages, subsequently vamp2 in the OB and
      telencephalon increased during seaward migration, corresponding well with
      development of the olfactory nervous system. Both stx1s in the OB and stx1b in
      the telencephalon were elevated in the seaward period, whereas stx1a in the
      telencephalon increased continuously until the feeding period. Both stx1s in the
      telencephalon increased in the last phase of upriver migration, possibly related
      to the retrieval of imprinted memory. Our results indicated the involvement and
      distinct roles of upregulated snares in synaptic plasticity for olfactory
      imprinting and/or olfactory memory retrieval in Pacific salmon.

PMID- 30236911
TI  - Fasting and refeeding induce differential changes in hypothalamic mRNA abundance
      of appetite-associated factors in 7 day-old Japanese quail, Coturnix japonica.
AB  - There is little information regarding effects of fasting on feeding behavior and
      hypothalamic physiology in young Japanese quail. The aim was thus to measure food
      intake and hypothalamic mRNA in response to fasting and refeeding. Five d-old
      quail ate little during the dark cycle. Food intake was greatest during the first
      2 h of the light cycle. Six day-old quail fasted for 6 h ate the most during the
      first 15 min of refeeding. In 7 d-old quail, 3 h of fasting up-regulated
      hypothalamic neuropeptide Y (NPY), NPY receptor sub-type 2 (NPYR2), agouti
      related peptide (AgRP), orexin receptor 2 (ORXR2), melanocortin receptors 3 and 4
      (MC3R and MC4R, respectively), and neuropeptide S (NPS) and decreased
      corticotropin-releasing factor receptor sub-type 1 (CRFR1) mRNA. Quail fasted for
      3 h and refed for 1 h had greater NPY, AgRP, POMC, and MC3R but less CRFR1 mRNA
      than fed quail. Quail fasted for 6 h expressed more NPY, NPYR1, NPYR2, and MC3R
      and less ORXR2, prolactin releasing peptide (PrRP), cocaine- and amphetamine
      regulated transcript (CART), and calcitonin (CAL) mRNA than fed quail. Quail
      fasted for 6 h and refed for 1 h expressed more NPY, NPYR1, NPYR2, AgRP, MC3R,
      MC4R, and NPS and less galanin, ORXR2, PrRP, CART, and CAL mRNA than fed birds.
      Hence, fasting induced changes in hypothalamic mRNA, with the largest changes
      occurring in genes associated with NPY and melanocortin signaling. Most genes
      remained elevated or downregulated after refeeding, suggesting that there was a
      time lag for transcription to respond to compensatory feeding.

PMID- 30236912
TI  - Predation experience underlies the relationship between locomotion capability and
      survival.
AB  - The positive relationship between locomotion performance and survival under
      predation has long been suggested yet seldom demonstrated with direct evidence.
      We investigate the effects of predator exposure on locomotion capacity (both fast
      start escape and critical swimming performance), survival under predation and the
      relationships between these factors in juvenile Chinese bream (Parabramis
      pekinensis). This study aims to test whether there is a positive relationship
      between the above factors and whether such relationships are context dependent
      (i.e., with or without 20 d of predator exposure). We found that predator-exposed
      Chinese bream showed higher rates of survival under predation and improved fast
      start swimming performance compared with individuals not exposed to predation. At
      individual level, no relationship was found between survival and any locomotion
      performance component in the no-predator group, but mean fast-start swimming
      speed, maneuverability and responsiveness were all positively related to survival
      in the predator group after 20 d of exposure. This finding indicates that the
      recognition of and vigilance for predators achieved through predation experience
      can be crucial preconditions for prey to employ the fast-start escape response,
      especially to escape ambush predators. Furthermore, a tradeoff was observed
      between the critical and fast-start swimming performances in the predator group,
      but not in the no-predator group, which may have been due to the intensified
      competition throughout the entire locomotion-support system (e.g., energy,
      proportions of slow- and fast-twitch muscle fibers) between critical and fast
      start swimming because the increased demand for fast-start escape capacity
      constrains (or compromises) critical swimming performance under the threat of
      predation.

PMID- 30236913
TI  - Atrial fibrillation frequency tracking in ambulatory ECG signals: The
      significance of signal quality assessment.
AB  - An approach to atrial fibrillation (AF) frequency tracking in long-term
      ambulatory ECG recordings is presented, comprising f-wave extraction, dominant
      atrial frequency (DAF) tracking, and signal quality assessment. Since poor signal
      quality is commonly encountered in ambulatory monitoring, a recently proposed
      index is employed to assess f-wave signal quality in a database containing 38
      patients with permanent AF. The index ensures that DAF outliers, typically
      associated with poor-quality segments, are excluded from further analysis. 40% of
      all 5-s signal segments were excluded from the database due to poor quality. The
      exclusion of DAF outliers significantly reduces the standard deviation of the
      frequency estimates (p<=0.01), allowing more reliable evaluation of the
      difference between day- and night-time DAF. The results show that signal quality
      assessment plays a central role in DAF tracking, and therefore should be employed
      in ambulatory monitoring.

PMID- 30236914
TI  - Varicose veins due to reflux in a tortuous sartorius muscle vein.
AB  - In daily phlebology practice, duplex ultrasound may sometimes reveal unusual
      pathways of reflux. A 46-year-old woman presented with heaviness and pain at the
      medial side of the left thigh after exercise. A tortuous intramuscular course of
      a large refluxing vein was seen in the sartorius muscle in connection with a
      femoral vein perforator cranially and the below-knee great saphenous vein
      distally. Magnetic resonance imaging confirmed these findings. Treatment
      consisted of a combination of foam sclerotherapy, radiofrequency ablation, and
      phlebectomies.

PMID- 30236915
TI  - The validity and reliability of the Swaymeter for postural sway measurement in
      typically developing children aged between 7-12 years.
AB  - BACKGROUND: The Swaymeter is a simple devicefor measuring postural sway. It
      consists of a 40-cm-long rod with a vertically mounted pen at the end of the rod
      that measures the displacement of the body at waist level. RESEARCH QUESTION:
      This device could be an effective tool for measuring postural sway in children.
      However, the validity and reliability of the Swaymeter in children has not been
      evaluated. In this study, we aimed to evaluate the validity and reliability of
      the Swaymeter in typically developing children aged 7-12 years. METHOD: The
      Swaymeter procedure was randomly measured in quiet bipedal stance under 4
      conditions: eyes open and eyes closed on the floor, eyes open and eyes closed on
      foam, 30 s were performed in each condition. There were 15 children participated
      in the validity study. The postural sway was measured concurrently with the
      motion capture system with two reflective markers on the top of the pen and 12th
      thoracic vertebra level in three trials with four testing conditions.
      Additionally, 36 children participated in test-retest reliability. Three
      measurements were performed on the same day and one week later. RESULTS:
      Swaymeter had a moderate to good correlation with motion capture system (r =
      0.637-0.979). The test-retest reliability of the Swaymeter showed moderate to
      good reliability for immediate test-retest (ICC = 0.51-0.87). However, inter
      session reliability revealed moderate to good reliability except for the AP
      variable that showed low reliability. Good to excellent reliability was found in
      sway area variable (ICCs between 0.74 and 0.92) for all measurements.
      SIGNIFICANCE: Postural sway measure by Swaymeter was valid and reliable in
      typically developing children aged 7-12 years and suitable for applying to assess
      postural sway in typically developing children.

PMID- 30236916
TI  - High incidence of posterior glenoid dysplasia of the shoulder in young baseball
      players.
AB  - BACKGROUND: Rounding of the posterior glenoid rim is observed in young throwing
      athletes with internal shoulder impingement and is considered developmental
      dysplasia of the glenoid. The aim of our study was to determine the incidence
      rate of dysplastic changes of the glenoid within a group of 92 young baseball
      players. METHODS: The study group included 92 male baseball players, with a mean
      age of 14.63 years. Of these patients, 30 were diagnosed with Little Leaguer's
      shoulder and 62 with a painful baseball-throwing shoulder with no abnormal
      findings on x-ray. The posterior glenoid rim of the affected shoulder was
      compared with the contralateral nonpainful shoulder, with the 2 following
      outcomes measured on radiographs obtained using the modified Bernageau imaging
      method: the distance between the anterior and posterior glenoid rims and the
      presence or absence of dysplasia of the posterior glenoid rim. RESULTS: The mean
      distance between the anterior and posterior glenoid rims was significantly
      shorter in the painful shoulders (mean, 26 mm) than in the nonpainful shoulders
      (mean, 29 mm; P < .0001). Dysplasia of the posterior glenoid rim was identified
      in 89 painful shoulders (96.7%), with 9 cases (9.7%) identified on the unaffected
      contralateral side (P < .001). The presence of dysplasia was not correlated with
      the age at which baseball playing began. CONCLUSION: The incidence of dysplasia
      of the posterior glenoid rim is high (96.7%) among young baseball players with a
      painful shoulder. The identified dysplasia may be related to impaired development
      of the inferior peripheral secondary glenoid ossification center due to
      repetitive throwing.

PMID- 30236917
TI  - Multivariate linear regression model for source apportionment and health risk
      assessment of heavy metals from different environmental media.
AB  - The study evaluated source apportionment of heavy metals in vegetable samples
      from the potential sources of fertilizer, water and soil samples collected along
      the Changjiang River delta in China. The results showed that 25.72% of vegetable
      samples (Brassica chinensis L.) containing Pb, and Cd, Cu, Hg and Zn at
      relatively serious levels were from soil. Combined with principle component
      analysis (PCA) and cluster analysis (CA), the results of the spatial distribution
      of heavy metals in different environmental media indicated that fertilizer, water
      and soil were the main sources of heavy metals in vegetables. The results of
      multivariate linear regression (MLR) using partition indexes (P) showed that
      fertilizer contributed to 38.5%, 40.56%, 46.01%, 53.34% and 65.25% of As, Cd, Cu,
      Pb and Zn contents in vegetables, respectively. In contrast, 44.58% of As, 32.57%
      of Hg and 32.83% of Pb in vegetables came from soil and 42.78% of Cd and 66.97%
      of Hg contents in vegetables came from the irrigation water. The results of PCA
      and CA verified that MLR using P was suitable for determining source
      apportionment in a vegetable. A health risk assessment was performed; As, Cd and
      Pb contributed to more than 75% of the total hazard quotient (THQ) values and
      total carcinogenic risk values (Risktotal) for adults and children through oral
      ingestion. More than 70% of the estimated THQ and Risktotal is contributed by
      water and fertilizer. Therefore, it is necessary to increase efforts in screening
      limits/levels of heavy metals in fertilizer and irrigation water and prioritize
      appropriate pollution management strategies.

PMID- 30236918
TI  - Earthworms stimulate nitrogen transformation in an acidic soil under different Cd
      contamination.
AB  - In acidic Cd-contaminated soils, soil nitrogen conversion is inhibited and
      usually block nitrogen supply for plants. Earthworms are well known for improving
      soil properties and regulating various soil biogeochemical processes including
      nitrogen cycling. To figure out the effect and mechanisms of earthworms on soil
      nitrogen transformation in Cd-contaminated soil, ten treatments with and without
      A. robustus in five soil Cd concentration gradients were established. The
      tolerant concentration of A. robustus to Cd in the acidic soil is about 6 mg kg
      1. The potential ammonia oxidation of the acidic soils was very low, ranging from
      0.05 to 0.1 ug NO2--N g-1 d-1. Although AOA was more abundant in the acidic soil
      than AOB, AOA was inhibited by Cd pollution, while AOB showed some increase under
      Cd-stress. AOA may play a dominant role in ammonia oxidation in acidic soil, but
      the recovery of nitrification in Cd-contaminated acidic soil was probably due to
      the effect of AOB. Earthworms significantly increased soil pH, DOC, ammonium and
      PAO, thus promoted soil ammonification and potential nitrification, but had no
      significant effect on soil net nitrification. Correlation analysis results
      demonstrate that earthworms may promote soil PAO by increasing soil pH, NH4+-N
      content, and AOB abundance. This study could provide a theoretical basis for
      solving the problem of nitrogen-cycling-functional degradation and nitrogen
      supply in the process of phytoremediation of heavy metals-contaminated soils.

PMID- 30236919
TI  - Variation of bacterioplankton community along an urban river impacted by
      touristic city: With a focus on pathogen.
AB  - Bacterioplankton communities play a critical role in ecological processes in
      river systems, and shifts of their composition may impact microbial levels and
      raise public health concerns. The aim of this study was to comprehensively
      analyze the essential factors influencing bacterioplankton community, along with
      pathogen, and to estimate the health risk caused by the pathogens downstream of
      the Liushahe River, which is located in the famous touristic city Xishuangbanna.
      Results showed that wastewater treatment plants (WWTPs) and a subtropical
      recreational park impacted the bacterioplankton community and pathogen
      population, and potential pathogen identification demonstrated that 76 of 145
      reference genera were present in the river. Moreover, the bacterioplankton
      community and pathogen were differently impacted by environmental gradients, and
      SRP, NO2 and pH were main factors influencing bacterioplankton community while
      pathogen population was highly correlated with temperature and turbidity. In
      addition, it is noted that the pathogen population was dominated by
      bacterioplankton community and this might because the capacity of resistance
      invasion pathogen was determined by of bacterioplankton community diversity.
      Therefore, bacterioplankton community diversity can be used to control and
      predict the amount of pathogens. Quantitative microbial risk assessment (QMRA)
      also revealed that the infection risks of Escherichia coli (E. coli),
      Mycobacterium avium (M. avium), and Pseudomonas aeruginosa (P. aeruginosa) during
      five recreational activities, especially water-based activities in the touristic
      city, were greater than that in natural areas and mostly exceeded the U.S. EPA
      risk limit for recreational activities. Our study offered the first insight into
      the potential relationship between the bacterioplankton community and bacterial
      pathogens within a touristic river.

PMID- 30236920
TI  - Influence of potassium concentration gradient on stable caesium uptake by Calla
      palustris.
AB  - The effect of potassium (K) concentration gradient on stable caesium (Cs) uptake
      by Calla palustris was studied under hydroponic conditions after eight-day
      exposure in a greenhouse experiment. The plants were exposed to two different
      concentrations of Cs (provided as 0.5 and 1 mM CsCl) and five different
      concentrations of K (provided as K2SO4 in 0.5, 1, 2, 5, and 10 mM). The results
      indicate negative dependence of Cs uptake on K concentrations for both Cs
      treatments. The application of K reduced the transfer of stable Cs from water to
      plant by about 44-72% for 0.5 mM CsCl and 56-74% for 1 mM CsCl. The highest
      efficiency of Cs removal from water was observed for plants in K+ deficient
      solutions (plants starving), with an efficiency 8.0% for plants cultivated in 0.5
      mM CsCl and 9.4% for plants in 1 mM CsCl. An increasing concentration of K also
      supported translocation of Cs from roots to leaves. Higher translocation was
      observed for the treatments with lower level of Cs, where the concentration of Cs
      in leaves became higher than that in roots. The Cs uptake and translocations were
      affected not only by the external concentration of K, but also the external
      concentration of stable Cs. A high concentration of K in the environment protects
      the food chain from Cs uptake by plants, but lowers the efficiency of
      phytoremediation techniques.

PMID- 30236921
TI  - Distribution and transformation of lead in rice plants grown in contaminated soil
      amended with biochar and lime.
AB  - This study aimed to investigate the effects of rice straw biochar and lime (RBL)
      on the remediation of lead (Pb)-contaminated soil and mitigation of Pb
      translocation in rice plants by using pot experiments. Lead-contaminated soil
      collected from a farmland near a Pb-zinc (Zn) mine, biochar, limestone powder,
      and indica rice (Oryza sativa L.) were used in the present study. The
      experimental treatments included: (1) control (CK), (2) 2.5% biochar (RB1), (3)
      5% biochar (RB2), (4) 0.6% lime (L1), (5) 1.2% lime (L2), (6) 2.5% biochar + 0.6%
      lime (RBL1), and (7) 2.5% biochar + 1.2% lime (RBL2). The results revealed that
      the treatment with RBL was more efficient than the treatment with only biochar or
      lime in decreasing CaCl2-extractable Pb content in the soil by increasing soil pH
      and soluble sulfate content in the soil. Treatment with RBL reduced in the
      accumulation of Pb in the shoot of rice plants, this was mainly attributed to the
      decrease in the concentration of available Pb in the soil. The RBL2 treatment not
      only decreased the concentration of Pb in brown rice by 84.33% and Pb
      distribution in rice embryo, but also increased rice yield by 53.38% from that of
      the control. Further, unlike biochar treatment, RBL and lime treatments decreased
      the translocation of Pb in rice plants. The RBL treatment increased the
      proportion of Pb distributed in the cell wall and reduced the mobility of Pb in
      plant tissues. Thus, application of biochar and lime in combination is more
      effective than their individual application in reducing the availability of Pb in
      the soil and Pb accumulation in brown rice.

PMID- 30236922
TI  - The antagonist and synergist potential of cholinium-based deep eutectic solvents.
AB  - The design of environmentally friendlier solvents has gained increasing relevance
      in the last decade. Deep eutectic solvents (DES) have recently emerged, with
      advantages like low-cost and putative lower environmental impact. However,
      information about DES toxicity is still scarce. This work aims to contribute to
      profiling the ecotoxicity of DES based on cholinium chloride ([Chol]Cl). Six DES
      were addressed, combining [Chol]Cl (as hydrogen bond acceptor - HBA) with
      ethylene glycol, glycerol, 1,2-propanediol, propionic acid, 1-propanol, and urea
      as hydrogen bond donors (HBD), in different molar ratios. The Microtox(r) Acute
      Toxicity Test, was used for assessing their toxicity towards the marine bacteria
      Allivibrio fischeri . Because the dissociation of DES in water is expected,
      analysis appraising the mixtures toxicity theory should be considered, which is a
      step forward in this field. This analysis suggested that [Chol]Cl and all HBD
      with the exception of propionic acid:[Chol]Cl 1:2 and 4:1 behave
      antagonistically, which is contrary to what has been suggested previously. The
      most extreme cases are Urea:[Chol]Cl and 1-Propanol:[Chol]Cl, with EC50 values
      higher than their starting materials dosed singly, configuring very promising and
      biocompatible alternative solvents. Toxicity was found to be dependent on DES
      composition, as well as on molar proportions of the starting materials.

PMID- 30236923
TI  - Sonic hedgehog signaling regulates the mammalian cardiac regenerative response.
AB  - Certain organisms, including zebrafish, are capable of complete cardiac
      regeneration in response to injury. This response has also been observed in
      newborn mice, although in this case, the regenerative capacity is lost at
      approximately one week of age. The mechanisms regulating this short temporal
      window of cardiac regeneration in mice are not well understood. Here, we show
      that sonic hedgehog (Shh) signaling modulates the neonatal mouse regenerative
      response. In particular, we demonstrate that following apical resection of the
      heart on postnatal day 1, mice activate Shh ligand expression and downstream
      signaling. This response is largely absent when surgery is performed on non
      regenerative, postnatal day 7 pups. Furthermore, an enhanced cardiac regeneration
      response was detected in ptch heterozygous mice which have a genetically-based
      constitutive increase in Shh signaling. We further show that Shh ligand is
      produced in the myocardium by non-myocytes and appears to regulate cardiomyocyte
      proliferation, as well as the recruitment of monocytes/macrophages to the
      regenerating area. Finally, we demonstrate that a small molecule activator of Shh
      signaling promotes heart regeneration, whereas an inhibitor of Shh signaling
      impairs the regenerative response. Together, these results implicate Shh
      signaling as a regulator of mammalian heart regeneration and suggest that
      modulating this pathway may lead to new potential therapies for cardiovascular
      diseases.

PMID- 30236925
TI  - Breast Cancer: Metastasis, Molecular Subtypes, and Overweight and Obesity in
      Veracruz, Mexico.
AB  - INTRODUCTION: We assessed the association between overweight, obesity, and morbid
      obesity with the incidence of the most aggressive breast cancer subtypes in
      women. METHODS AND MATERIALS: A cross-sectional study was performed. We conducted
      a record review to identify the following aspects: body mass index,
      sociodemographic features, tumor characteristics, and reproductive and molecular
      aspects. Descriptive statistics and univariate analysis were performed to
      identify the association between the molecular subtypes and the study variables.
      In addition, we used multivariate analysis to identify the association between
      obesity and the presence of metastatic lymph nodes. RESULTS: We included 1446
      women with an average age of 52.5 +/- 12.1 years. Of the 1446 patients, 47% were
      premenopausal and 75% were overweight. Univariate analysis indicated a
      statistically significant association between obesity and advanced disease stage,
      as well as nulliparity and multiparity. Similar results were found for women with
      morbid obesity. Model 1 of the multivariate analysis showed an association
      between the presence of metastatic lymph nodes and obesity (odds ratio [OR], 1.6;
      P = .008) and histologic grade 2 or 3 (OR, 2.4; P = .003). Using model 2, an
      association was identified between an advanced disease stage and 2 factors:
      morbid obesity (OR, 1.9; P = .02) and positive human epidermal growth factor
      receptor 2 (OR, 1.8; P = .045). CONCLUSION: We found that obesity is associated
      with the more advanced stages of breast cancer. Further studies are needed to
      evaluate the role of obesity in breast cancer progression in women.

PMID- 30236924
TI  - Interaction of Abl Tyrosine Kinases with SOCS3 Impairs Its Suppressor Function in
      Tumorigenesis.
AB  - Suppressor of cytokine signaling 3 (SOCS3) is involved in Bcr-Abl-induced
      tumorigenesis. However, how SOCS3 interacts with Bcr-Abl and is regulated by Abl
      kinases remains largely unknown. Since c-Abl plays a critical role in
      tumorigenesis, we asked whether SOCS3 is regulated by c-Abl-dependent
      phosphorylation. Here, we found that SOCS3 interacted with all three Abl kinases
      (Bcr-Abl, v-Abl, and c-Abl), and SH1 domain of the Abl kinases was critically
      required for such interaction. Furthermore, the SH2 domain of SOCS3 was
      sufficient to pull down the SH1 domain but not the full length of Bcr-Abl.
      Importantly, SOCS3 was highly tyrosine phosphorylated by c-Abl, leading to
      impairment of its ability to suppress JAK8+72 activity. In addition, disrupting
      the tyrosine phosphorylation of SOCS3 promoted apoptosis of c-Abl-expressing
      cells and impeded xenograft growth of these tumor cells in nude mice. The results
      demonstrate that SOCS3 is highly tyrosine phosphorylated by c-Abl and that
      tyrosine phosphorylation of SOCS3 is required for the survival and tumorigenesis
      of certain cells. Our findings provide novel insights into complicated mechanisms
      underlying the oncogenic function of Abl kinases.

PMID- 30236926
TI  - Heating-up control with delay-free output prediction for industrial jacketed
      reactors based on step response identification.
AB  - To improve the heating-up control performance for industrial jacketed reactors
      typically involved with long input delay, a predictor-based two-degree-of-freedom
      (2DOF) control scheme is proposed for the heating-up process operation, based on
      model identification from a practical step response test. By performing a simple
      step test (i.e., turning on the electrical heater with certain power (e.g., 50%
      or 100% of the heating power) to observe the heating-up temperature response), a
      transfer function identification method is developed to establish an integrating
      type process model with time delay for describing fundamental dynamics of the
      heating-up response. Based on the identified model, a predictor-based 2DOF
      control structure is established, where the delay-free output prediction is
      obtained by constructing two filters. The 2DOF controllers are analytically
      derived by proposing the desired transfer functions for the set-point tracking
      and load disturbance rejection, respectively. There is a single adjustable
      parameter in each controller (or filter), which may be monotonically tuned to
      obtain the desired control (or prediction) performance. Illustrative examples
      from the existing references and a practical application to a 4-liter jacketed
      reactor for pharmaceutical crystallization are given to demonstrate the
      effectiveness and advantage of the proposed identification and control methods in
      comparison with the existing methods.

PMID- 30236927
TI  - Sparse decomposition method based on time-frequency spectrum segmentation for
      fault signals in rotating machinery.
AB  - The impulse signal in large rotating machinery with damage fault is sparse, weak,
      coupled, and even nonperiodic in intermittent operation. To extract this complex
      signal is a key topic in machinery fault diagnosis. Sparse decomposition (SD) has
      excellent adaptability in describing arbitrary complex signals based on over
      complete dictionary. However, the pursuit speed of best atom is a serious
      drawback. To alleviate this, a method of sparse decomposition based on time
      frequency spectrum segmentation (SD-TFSS) is introduced. Generalized S transform
      (GST) provides the capability to show the distribution of vibration signals, but
      the resolution is susceptible to noise, multiresolution generalized S-transform
      (MGST) is developed to generate multiresolution time-frequency spectrums. Then,
      spectrums fusion with an appropriate threshold is adopted to acquire
      multiresolution binary spectrums and produce an optimal binary spectrum. From
      this optimal binary spectrum, all the connectivity areas are extracted and marked
      by spectrum segmentation. Thus, an optimal library can be constructed by
      selecting the optimal atoms of every connectivity area, and the signal can be
      expressed with this library. We conduct simulations and experiments demonstrating
      that the proposed method performs well with lower pursuit complexity, higher
      decomposition efficiency, and better approximation precision.

PMID- 30236928
TI  - Dissipativity-based non-fragile sampled-data control design of interval type-2
      fuzzy systems subject to random delays.
AB  - This paper investigates the beta-dissipativity-based reliable non-fragile sampled
      data control problem for a class of interval type-2 (IT2) fuzzy systems. In
      particular, it is allowed to have randomly occurring time-varying delays in the
      controller design, which are modeled by Bernoulli distributed white noise
      sequences. Precisely, the IT2 fuzzy model and the non-fragile sampled-data
      controller are formulated by considering the mismatched membership functions. By
      constructing an appropriate Lyapunov-Krasovskii functional, a set of delay
      dependent conditions is derived to guarantee that the closed-loop IT2 fuzzy
      system is strictly <Q,S,R>-beta-dissipative. Moreover, the gain matrices of
      feedback reliable non-fragile sampled-data controller are derived in terms of
      linear matrix inequalities (LMIs), which can be solved by using existing LMI
      solvers. Two numerical examples are eventually given to illustrate the
      applicability and effectiveness of the proposed controller design technique.

PMID- 30236929
TI  - Homogenate-assisted high-pressure disruption extraction for determination of
      phenolic acids in Lonicerae Japonicae Flos.
AB  - An effective method based on the combined homogenate-assisted high-pressure
      disruption extraction (HHPDE) was applied to the extraction and determination of
      the main phenolic acid compounds from Lonicerae Japonicae Flos. The optimized
      HHPDE showed competitive advantage in yield (The extraction yields of NCA, CA,
      3,5DCA and 4,5DCA in HHPDE were 1.21, 1.08, 1.06 and 1.17 fold higher than those
      in UAE), time-saving (<5 min) and relative low temperature requirement (4-16 
      degrees C) compared to HRE and UAE. Furthermore, the HHPDE method behaved a good
      repeatability and reproducibility according to the HPLC. The mentioned HHPDE
      method is firstly applied in the extraction and quantification of neochlorogenic
      acid chlorogenic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid in
      Lonicerae Japonicae Flos. This work provided an excellent alternative for the
      extraction and quantification of thermosensitive from plants.

PMID- 30236930
TI  - Identification of commercial and recreational vessels coated with banned
      organotin paint through screening of tin by portable XRF.
AB  - The most effective biocide used historically in antifouling paints is tributyltin
      (TBT). However, due to its extreme toxicity to non-target organisms and its
      persistence in the environment, the use of TBT and other organotin compounds
      (OTCs) was restricted in EU on leisure boats and ships in 1989 and 2003,
      respectively. Nevertheless, studies worldwide still report TBT to be released
      from both ships and leisure boats. Here, we present a new application for a field
      portable X-ray fluorescence spectrometer (XRF) used for screening for organotin
      paint through measurements of tin (Sn) on leisure boats and ships. Measurements
      on ships built after the restrictions showed concentrations of up to 68 MUg
      Sn/cm2, likely due to impurities of inorganic Sn, as shown through chemical
      analysis of 21 organotin-free paints. A threshold value of 100 MUg Sn/cm2 is
      suggested, where exceedance indicates presence of OTCs. Screening with the XRF
      method showed 10% of the commercial vessels (n = 30) and 23-29% of leisure boats
      (n = 693, investigated in this and in a previous study) to hold concentrations
      exceeding 100 MUg Sn/cm2. The XRF technique presented here provides a useful tool
      for quick screening and identification of vessels holding banned organotin paint.

PMID- 30236931
TI  - Recovery of cutting fluids and silicon carbide from slurry waste.
AB  - The wafer slicing process generates large amounts of slurry waste. The recovery
      of cutting oil and abrasives from slurry waste can reduce both the cost and
      environmental damage. A process combining magnetic precipitation and flocculation
      was developed for the recovery of cutting oil. A magnetic precipitation tank was
      employed for storage of the slurry and acceleration of the settlement of
      suspended particles. The larger particles further aggregate upon adding a non
      aqueous flocculant comprising polyacrylamide (PAM) and ethylene glycol (EG). The
      recycled oil product is obtained by centrifugation and bag filtration. The
      physical properties and wafer dicing tests indicate that the recycled oil is
      qualified. Wafer manufacturers can thus reduce costs by using this process to
      produce recycled oil. A magnetic reactor with alkaline aqueous successfully
      recycled the SiC powder from the slurry waste by converting all the silicon
      species into sodium silica for further use. The results demonstrate that the
      magnetic reactor is able to remove most metal species and that the alkaline
      aqueous medium can recover all the Si substances in a sodium silicate solution,
      also called water glass.

PMID- 30236932
TI  - Cutting frequency effect on barium phytoextraction by macrophytes in flooded
      environment: A field trial.
AB  - In anoxic environmental conditions and with a drastic reduction of the redox
      potential, the barium sulphate used in petroleum drilling fluids becomes a hazard
      to the ecosystem. A field study was conducted in Brazil in an area with a history
      of accidental Barium (Ba) contamination to evaluate the role of frequent plant
      cutting on phytoremediation. The plant species Typha domingensis and Eleocharis
      acutangula, cultivated in a combined plantation, were subjected to four different
      cut frequencies: every 90 days (four cuts), 120 days (three cuts), 180 days (two
      cuts), or 360 days (one cut). The total amount of Ba extracted from the soil by
      the plants was evaluated for each treatment and at different soil depths Overall,
      total Ba in the soil decreased the most dramatically for cut frequencies of 120
      (37.83%) and 180 (47.73%) days at 0-0.2 m below the surface, and with cut
      frequencies of 120 (51.98%) and 360 (31.79%) at 0.2-0.4 m depth. Further, total
      Ba in the plant biomass was greatest in the 120 and 360-days frequency groups.
      Thus, cuts at intervals of 120 days or more are associated with high levels of Ba
      in the plant tissue and a decrease of soil Ba.

PMID- 30236933
TI  - Stabilization/solidification characteristics of organic clay contaminated by lead
      when using cement.
AB  - Research about cement treated soil has examined various characteristics of
      strengthened and stabilized soil, but has mainly focused on either the unconfined
      compressive strength or potentially toxic element (PTE) stabilizing results
      respectively in response to cement dosing. This study investigates how factors
      including cement concentration, lead concentration, humic/fulvic acid content and
      curing age affect these two geotechnical and environmental characteristics. A
      laboratory study was conducted to measure unconfined compressive strength, and
      lead leaching under several test conditions. Knowing that humic acid and fulvic
      acid can weaken cementation in cement treated soil but can stabilize PTEs such as
      lead by different chemical reactions, it was found that the acids generally
      reduce lead stabilization in cement treated soil. In addition, the stabilized
      strength reaches a peak at a specific lead content in soil. Finally, scanning
      electron microscopy was used to observe more detailed changes and mechanisms.

PMID- 30236934
TI  - Transformation of novel polyfluoroalkyl substances (PFASs) as co-contaminants
      during biopile remediation of petroleum hydrocarbons.
AB  - Aqueous film forming foams (AFFFs) containing perfluoroalkyl and polyfluoroalkyl
      substances (PFASs) are commonly deployed to extinguish hydrocarbon fuel fires,
      resulting in petroleum hydrocarbons coexisting with PFASs in contaminated soil.
      Nutrient-amended and aerated biopiles used for petroleum hydrocarbon
      bioremediation could cause unintended transformation of polyfluorinated
      substances into perfluoroalkyl carboxylates (PFCAs). The study sought to examine
      environmental behaviors of PFASs in engineered treatment facilities by monitoring
      AFFF-derived PFASs under three nutrient conditions. The influence of nutrient
      levels on degradation kinetics and efficiency was found to vary between the two
      chemical classes and among individual PFASs. A high number of compounds including
      the zwitterionic polyfluoroalkyl betaines that have aged in the field for two
      years were continuously biotransforming in lab reactors, demonstrating their slow
      kinetics and environmental persistence. The low yield to PFCAs implies that the
      processes such as the formation of bound residues or irreversible sorption might
      play a major role in reducing detectable levels of zwitterionic PFASs. The high
      persistence of betaines was further confirmed by the behaviors of a freshly
      spiked sulfonamide betaine. The study demonstrated complex chemical dynamics in
      AFFF-impacted soils and the challenges for predicting the fate of PFASs in soil
      biopiling facilities.

PMID- 30236935
TI  - TiC doped palladium/nickel foam cathode for electrocatalytic hydrodechlorination
      of 2,4-DCBA: Enhanced electrical conductivity and reactive activity.
AB  - Titanium carbide (TiC) with excellent electrical conductivity, chemical and
      thermal stabilities has been recognized as one of the most promising
      electrocatalysts. A novel cathode, titanium carbide doped palladium/nickel foam
      (TiC-Pd/Ni foam), was synthesized via electroless deposition to improve the
      performance of Pd/Ni foam in electrocatlytic hydrodechlorination (ECH). TiC can
      be co-precipitated onto the surface of cathode during galvanic replacement
      reaction between Pd(II) solution and Ni foam. Both constant potential and
      constant current tests proved that TiC-Pd/Ni foam cathode performed remarkably
      higher activity for 2,4-dichlorobenzoic acid (2,4-DCBA) than Pd/Ni foam cathode,
      owing to the excellent conductivity of TiC and enhanced water dissociation over
      TiC-Pd/Ni foam cathode. Under the optimized reaction conditions of -0.85 V (vs
      Ag/AgCl), electrolyte of 10 mM and initial pH of 4, 99.8% of aqueous 2,4-DCBA
      (0.2 mM) was removed within 90 min. The removal process of the aqueous 2,4-DCBA
      obeyed first-order decay kinetic model. Over 86.3% of 2,4-DCBA can still be
      removed by TiC-Pd/Ni foam cathode in the fifth consecutive run within 120 min,
      which was much higher than that of Pd/Ni foam cathode (37.5%). Consequently, TiC
      Pd/Ni foam cathode was a promising design for enhanced ECH activity and reduced
      operation cost.

PMID- 30236936
TI  - Hybrid porous magnetic bentonite-chitosan beads for selective removal of
      radioactive cesium in water.
AB  - Easy-to-obtain magnetic bentonite-chitosan hybrid beads (Bn-CTS) were prepared by
      immobilizing bentonite within a porous structure of chitosan beads to achieve a
      hybrid adsorption effect for the removal of cesium ion (Cs+) from water. The
      hybrid adsorbent, which had a porous structure and abundant binding sites
      contributed by both chitosan and bentonite, ensured superb adsorption
      characteristics. The paramagnetic character of the beads enabled their facile
      separation for recycling. The chitosan/bentonite ratio, pH and contact time were
      optimized to achieve the optimal Cs+ efficiency, and the adsorption kinetics and
      isotherms were thoroughly discussed. The adsorption kinetics obeyed the pseudo
      second-order model, and the best fitted equation for equilibrium data was the
      Langmuir isotherm model. The maximum adsorption capacity of the bentonite
      chitosan beads was 57.1 mg g-1. The adsorbent had excellent selectivity towards
      Cs+ adsorption in the presence of abundant cations (Li+, Na+, K+ and Mg2+). The
      adsorbent was able to be recycled by treating the beads with 0.1 mol L-1 of MgCl2
      to quantitatively desorb Cs+ from the beads. Overall, the magnetic bentonite
      chitosan beads can be used as a highly efficient adsorbent for radioactive waste
      disposal and management.

PMID- 30236937
TI  - Identification of fragmentation mechanism and risk analysis due to explosion of
      cylindrical tank.
AB  - This study presents a completely new methodology for fragmentation analysis due
      to the explosion of cylindrical tanks. The identification of fragments' kinematic
      parameters was accomplished with an exact system of differential equations of
      motion with good convergence and high accuracy of numerical results. The
      fluctuation effect of the aerodynamic force of the fragments on their range is
      interpreted by statistical distributions. The direction and intensity of the
      fragments' initial velocity are determined by the inertial model. An original
      probabilistic mass method is proposed to represent the discrete distribution of
      the number of generated fragments. The correlation between the number and mass of
      the fragments was established by Monte Carlo simulation. The estimation of the
      fracture lines was carried out by the tank stress mapping procedure using data
      from the ANSYS software. The identification of potential fracture lines with the
      knowledge of the number-to-mass dependence of the fragments allows a reliable
      estimate of the shape of the generated fragments. The estimated sectoral risk due
      to tank fragmentation is consistent with literary accident data. The presented
      methodology can be fully applied to the assessment of the risk of other types of
      tanks and process installations.

PMID- 30236938
TI  - A novel dehydrogenase 17beta-HSDx from Rhodococcus sp. P14 with potential
      application in bioremediation of steroids contaminated environment.
AB  - Steroids are endocrine disrupting compounds in human and are distributed in
      various environments. Our previous study showed that a marine bacterium
      Rhodococcus sp. P14 was able to efficiently degrade one typical steroid
      estradiol. In this study, we showed that P14 could also use other steroids,
      including estriol and testosterone, as sole carbon source for growth. Two
      dehydrogenation products, 16-hydroxestrone and androst-4-ene-3, 17-dione, were
      detected during estriol and testosterone degradation, respectively. By screening
      the genome, a short chain dehydrogenase gene was identified and named as 17beta
      HSDx. Expression of 17beta-HSDx was induced in P14 when estriol, estradiol or
      testosterone was used as single carbon source. In addition, 17beta-HSDx was shown
      to have dehydrogenation ability of transforming estriol to 16-hydroxestrone,
      estradiol to estrone and testosterone to androst-4-ene-3, 17-dione. This is the
      first short chain dehydrogenase identified in bacteria with dehydrogenation
      ability on various steroids substrates. Overall, this study reveals that 17beta
      HSDx has potential application in the bioremediation of steroids contaminated
      environment.

PMID- 30236939
TI  - In situ fabrication of highly active gamma-MnO2/SmMnO3 catalyst for deep
      catalytic oxidation of gaseous benzene, ethylbenzene, toluene, and o-xylene.
AB  - gamma-MnO2, SmMnO3, and gamma-MnO2/SmMnO3 catalysts were prepared by facile
      methods, wherein the SmMnO3 (SMO) perovskite was synthesized through one-step
      calcination and the gamma-MnO2/SmMnO3 was formed by an in situ growth of gamma
      MnO2 on the surface of SMO. These materials ware characterized by XRD, SEM
      mapping, N2-adsorption, XPS and H2-TPR to investigate their textural properties.
      Compared with that of SMO and gamma-MnO2, the gamma-MnO2/SMO shows better
      performance for catalytic oxidation of aromatic VOCs in wet air (10 vol.%), which
      may be attributed to its higher surface molar ratio of lattice oxygen to adsorbed
      oxygen (Olatt/Oads) and better low-temperature reducibility. Besides, for gamma
      MnO2/SMO catalyst, a successive oxidation route and the inner principle of BETX
      (benzene, ethylbenzene, toluene, and o-xylene) oxidation were also revealed via
      various tests and a comprehension of dynamics investigation. Meanwhile, the
      experiments under simulated realistic exhaust conditions displayed that the gamma
      MnO2/SmMnO3 is also a good catalyst with high stability for aromatic VOCs
      oxidation, and fulfilled endurability to high humidity (20 vol.%).

PMID- 30236940
TI  - Unraveling complex removal behavior of landfill leachate upon the treatments of
      Fenton oxidation and MIEX(r) via two-dimensional correlation size exclusion
      chromatography (2D-CoSEC).
AB  - The complex removal behavior of stabilized landfill leachate was explored for the
      treatments of Fenton oxidation (FnO) and magnetic ion exchange (MIEX(r)) resin
      using two-dimensional correlation size exclusion chromatography (2D-CoSEC) and
      fluorescence excitation emission matrix-parallel factor analysis (EEM-PARAFAC).
      The overall removal rates of the bulk parameters (~45% for dissolved organic
      carbon and ~78% for UV absorbance) were similar between the two treatment
      options, while distinct differences were found with respect to different
      molecular sizes and chemical composition. The resin treatment eliminated humic
      substances (HS) and low molecular weight acid (LMWA) fractions to a greater
      extent than other fractions (i.e., HS: 62% and LMWA: 99%), while low molecular
      weight neutral (LMWN) and biopolymers (BP) fractions were more effectively
      treated by the FnO with the removal rates of 56% and 92%, respectively. The 2D
      CoSEC further revealed that the sequential or preferential changes of different
      size fractions with increasing the resin or H2O2 were opposite between the two
      treatment options in the order of HS -> LMWA -> LMWN -> BP for MIEX(r). Due to
      their complementary roles in treating leachate, the combined processes removed a
      wider ranges of different molecular sizes compared to the single operation.

PMID- 30236941
TI  - pH-mediated reversible fluorescence nanoswitch based on inner filter effect
      induced fluorescence quenching for selective and visual detection of 4
      nitrophenol.
AB  - Being a common hazardous waste, 4-nitrophenol (4-NP) has caused a serious threat
      to humans and environment. Therefore, rapid and selective detection of 4-NP,
      especially using a simple and portable instrument, is highly desired for human
      health and environmental monitoring. Herein, we develop a novel pH-mediated
      reversible fluorescence nanoswitch for selectively detecting 4-NP by using water
      soluble fluorescent polymer carbon dots (PCDs) as a probe. The fluorescence of
      PCDs can be quenched by 4-NP via inner filter effect (IFE) because its excitation
      spectrum well overlaps with the absorption spectrum of 4-NP under alkaline
      condition. However, an obvious blue shift of the absorption peak of 4-NP occurs
      under acidic condition, causing the fluorescence recovery of PCDs due to the
      disappearance of IFE. On the basis of this principle, a pH-mediated reversible
      fluorescence nanoswitch was constructed and a broad linear range was obtained
      from 0.5 to 60 MUM with a detection limit of 0.26 MUM for 4-NP. Furthermore, this
      approach was successfully applied to detect 4-NP in real water samples and a
      portable polyamide film-based sensor was developed for visual detection of 4-NP,
      which offers a promising platform for the detection of 4-NP in on-site and
      resource-poor settings.

PMID- 30236942
TI  - Ordered micro-mesoporous carbon from palm oil cooking waste via nanocasting in
      HZSM-5/SBA-15 composite: Preparation and adsorption studies.
AB  - This work reports the preparation of HZSM-5/SBA-15 micro-mesoporous materials
      with composite structure by mechanosynthesis and their use as templates to micro
      mesoporous carbons, with palm oil cooking waste as carbon source. HZSM-5/SBA-15
      composites were prepared in different mass proportions (25:75, 50:50 and 75:25)
      by a mechanosynthetic strategy. The palm oil waste was infiltrated into the
      template pores by a two-step procedure involving grinding followed by stirring
      the suspension in an oil solution and carbonization under inert atmosphere. SEM
      images showed the efficiency of mechanosynthesis for all mass proportions, while
      textural properties were strongly influenced by the presence of SBA-15. A
      comparison of 50% HZSM-5/SBA-15 mixture with pristine SBA-15 and uncalcined SBA
      15 as carbon templates evidenced that the 50% HZSM-5/SBA-15 mixture lead to the
      carbon with the highest surface area and pore volume. The resulting carbon
      material was studied as adsorbent to different dye molecules, including molecules
      with different charges and sizes. Results revealed that the carbon has a
      significantly higher affinity for cationic dyes, that the mesopore structure
      favors high diffusion rates and that the surface groups have a very high affinity
      for cationic dye molecules.

PMID- 30236943
TI  - Preparation of reduced graphene oxide nanosheet/FexOy/nitrogen-doped carbon layer
      aerogel as photo-Fenton catalyst with enhanced degradation activity and
      reusability.
AB  - In this manuscript, a novel reduced graphene oxide nanosheet/FexOy/nitrogen-doped
      carbon layer (rGS/FexOy/NCL) aerogel with FexOy NPs sandwiched between rGS and
      NCL was prepared via a two-step method. Their catalytic performance was evaluated
      in a photo-Fenton degradation of rhodamine B. It was found that rGS/FexOy/NCL
      aerogel represented higher degradation activity than the sum of rGS/NCL support
      and FexOy NPs, suggesting synergistic effect was established between support and
      reactive species. The degradation activity was investigated on the basis of
      aerogel usage, FexOy loading, H2O2 dosage, pH value and RhB concentration. To
      test stability and reusability, leaching experiments, cyclic experiments and
      structural analysis were carried out. Based on inhibitor experiment and
      intermediate detection, a possible catalytic mechanism and degradation pathway of
      RhB were proposed.

PMID- 30236944
TI  - Enhanced surface decontamination of radioactive Cs by self-generated, strippable
      hydrogels based on reversible cross-linking.
AB  - A self-generated, strippable hydrogel containing adsorbents was developed to
      remove the radioactive cesium from surfaces by adsorption for wide-area surface
      decontamination. Two aqueous polymeric solutions of polyvinyl alcohol (PVA) and
      phenylboronic-acid-grafted alginate (PBA-Alg) were easily applied to surfaces and
      subsequently self-generated a hydrogel based on the PBA-diol ester bond. Compared
      to the strippable coating and chemical gels, the PBA-diol ester bond-based
      hydrogel was easily peeled off the surfaces without a drying step due to its high
      elasticity, which is more practical and time saving. The resulting hydrogel
      displayed high 137Cs removal efficiencies of 91.61% for painted cement, 97.505%
      for aluminum, 94.05% for stainless steel, and 53.5% for cement, which was 2.3
      times higher than that of Decongel due to the presence of the adsorbent in the
      hydrogel having an excellent Cs distribution coefficient (3.34 * 104 mL/g).
      Moreover, the volume of radioactive waste generated after the surface
      decontamination could be reduced by a simple magnetic separation of the adsorbent
      from the used hydrogel, which can reduce the waste disposal cost. Therefore, our
      hydrogel system has great potential as a new, cost-effective surface
      decontaminant in various nuclear industry fields including wide-area
      environmental remediation after a nuclear accident or terrorist attack.

PMID- 30236945
TI  - Core-Shell Bimagnetic Nanoadsorbents for Hexavalent Chromium Removal from Aqueous
      Solutions.
AB  - Novel nanoadsorbents based on core-shell bimagnetic nanoparticles (CoFe2O4@gamma
      Fe2O3) with two different mean sizes were elaborated, characterized and applied
      as potential sorbents for Cr(VI) removal from aqueous solutions through
      magnetically assisted chemical separation. The nanoadsorbents were characterized
      by XRD, TEM, FTIR, XPS, potentiometric-conductometric titrations, BET and
      vibrating sample magnetometry. The influence of contact time, shaking rate, pH,
      pollutant concentration, temperature and competing ions on Cr(VI) adsorption were
      evaluated. The results were analyzed in the framework of Langmuir and Freundlich
      models to evaluate the maximum adsorption capacity and the extent of affinity.
      The nanoadsorbents showed a good selectivity for Cr(VI) adsorption and were more
      effective at pH = 2.5, with a shaking rate of 400 RPM. The adsorption process was
      spontaneous, endothermic and presented an increased randomness. The contact time
      required to reach the equilibrium was relatively short and the kinetic date
      followed the pseudo-second-order model. The maximum adsorption capacity was
      nearly 40% higher for the nanoadsorbent of smaller mean size due to its higher
      surface area. Regeneration studies revealed that the nanoadsorbents can be
      recovered for reuse. These results indicate that prepared nanoadsorbents can be
      used as a powerful tool for Cr(VI) removal from contaminated water.

PMID- 30236946
TI  - Mechanisms for light-driven evolution of environmentally persistent free radicals
      and photolytic degradation of PAHs on Fe(III)-montmorillonite surface.
AB  - Environmentally persistent free radicals (EPFRs) have been widely detected in
      superfund sites and atmospheric particles contaminated with organic contaminants,
      but the impacts of environmental factors such as light irradiation on the
      formation and evolution of EPFRs remain unclear. In the present study, in-situ
      irradiated Fourier transform infrared spectrometer and electron paramagnetic
      resonance were applied to probe the formation mechanisms of EPFRs during photo
      transformation of polycyclic aromatic hydrocarbons (PAHs) on montmorillonite
      surface. EPFRs were only detected on Fe(III)-montmorillonite containing PAHs with
      relatively high electron-donating ability, such as anthracene (ANT), but not in
      the systems of Fe(III)-montmorillonite spiked with phenanthrene or Na(I)
      montmorillonite. The 1/e lifetime of the EPFRs was much shorter under light
      irradiation (5.49 h) than in dark (30.3 h), suggesting that light irradiation
      facilitated the transformation of EPFRs. On the one hand, light irradiation
      promoted direct electron transfer from ANT to the mineral surface, accelerating
      the formation of PAHs-type radical cations. On the other hand, light irradiation
      induced the generation of reactive oxygen species, which facilitated the
      transformation from radical cations to oxygenic EPFRs, which finally led to ANT
      degradation. This work clarified the underlying mechanisms for EPFRs generation
      and evolution on clay minerals.

PMID- 30236947
TI  - Water defluoridation by Fe(III)-loaded sisal fibre: Understanding the influence
      of the preparation pathways on biosorbents' defluoridation properties.
AB  - Defluoridation properties of two Fe(III)-loaded plant biomass (Fe(III)-activated
      sisal fibre (Fe(III)-ASF) and post-alkalized Fe(III)-ASF (PA-Fe(III)-ASF))
      distinguished by preparation pathways through exclusion/inclusion of post
      alkalization are presented, with the aim of understanding the influence of post
      alkalization in the preparation pathway to their fluoride removal properties.
      Findings reveal that PA-Fe(III)-ASF shows higher chemical stability with removal
      efficiency increasing towards acidic conditions, whereas Fe(III)-ASF manifests a
      lower chemical stability with removal efficiency increasing (in a wider pH range)
      with the increase in pH. This is attributable to the nature of the interactions
      between Fe(III) and the biomass surface functional groups. The removal efficiency
      by PA-Fe(III)-ASF has a strong positive correlation (0.98) to the surface
      charge/speciation induced by pH and the reverse is true for the Fe(III)-ASF.
      These findings therefore suggest that the principal fluoride removal mechanism is
      electrostatic interactions and ligand exchange for PA-Fe(III)-ASF and Fe(III)
      ASF, respectively. Therefore, inclusion/exclusion of post-alkalization in
      preparation steps is an important aspect to consider in the production of Fe(III)
      loaded biosorbents for water defluoridation for acquisition of specific
      defluoridation properties.

PMID- 30236948
TI  - WASP (Write a Scientific Paper): Structuring a scientific paper.
AB  - Writing and publishing scientific papers have become requisites for all
      scientists (researchers and academics alike) to maintain their professional
      career. The prospects of writing a scientific paper are often regarded as
      somewhat daunting to the uninitiated. However a universal, well established
      structure format known as "IMRAD": i.e. Introduction, Methods, Results And
      Discussion has been established. This paper details this methodology.

PMID- 30236949
TI  - WASP (Write a Scientific Paper): The role of the pathology department in clinical
      research.
AB  - The pathology laboratory is the hub of investigatory medical care, and
      constitutes an invaluable asset for clinical research. A number of disciplines
      fall under the cap of a pathology laboratory. Researchers may gain access to such
      services provided ethical and laboratory administrative permissions have been
      granted. While establishing the research budget it is essential to have a clear
      understanding of what goes on behind the path lab curtains as this may impinge on
      what can and cannot be done, financially and otherwise. Indeed, the process is
      far more complex than just handing a specimen and obtaining the respective
      result. Infrastructure, material and human resources need to be quantified and
      their respective costing identified. Liaison with the laboratory section
      personnel facilitates the smooth provision of service and research outcomes.

PMID- 30236950
TI  - Reverse Isotopic Phenomenon in Drug Reaction with Eosinophilia and Systemic
      Symptoms.

PMID- 30236951
TI  - Multiobjective optimization to reconstruct biological networks.
AB  - Automated methods for reconstructing biological networks are becoming
      increasingly important in computational systems biology. Public databases
      containing information on biological processes for hundreds of organisms are
      assisting in the inference of such networks. This paper proposes a multiobjective
      genetic algorithm method to reconstruct networks related to metabolism and
      protein interaction. Such a method utilizes structural properties of scale-free
      networks and known biological information about individual genes and proteins to
      reconstruct metabolic networks represented as enzyme graph and protein
      interaction networks. We test our method on four commonly-used protein networks
      in yeast. Two are networks related to the metabolism of the yeast: KEGG and
      BioCyc. The other two datasets are networks from protein-protein interaction:
      Krogan and BioGrid. Experimental results show that the proposed method is capable
      of reconstructing biological networks by combining different omics data and
      structural characteristics of scale-free networks. However, the proposed method
      to reconstruct the network is time-consuming because several evaluations must be
      performed. We parallelized this method on GPU to overcome this limitation by
      parallelizing the objective functions of the presented method. The parallel
      method shows a significant reduction in the execution time over the GPU card
      which yields a 492-fold speedup.

PMID- 30236952
TI  - Rapid emergence of highly variable and transferable oxazolidinone and phenicol
      resistance gene optrA in German Enterococcus spp. clinical isolates.
AB  - The number of linezolid-resistant Enterococcus spp. isolates received by the
      National Reference Centre for Staphylococci and Enterococci in Germany has been
      increasing since 2011. Although the majority are E. faecium, clinical linezolid
      resistant E. faecalis have also been isolated. With respect to the newly
      discovered linezolid resistance protein OptrA, the authors conducted a
      retrospective polymerase chain reaction screening of 698 linezolid-resistant
      enterococcus clinical isolates. That yielded 43 optrA-positive strains, of which
      a subset was analysed by whole-genome sequencing in order to infer linezolid
      resistance-associated mechanisms and phylogenetic relatedness, and to disclose
      optrA genetic environments. Multiple optrA variants were detected. The originally
      described variant from China (optrAWT) was the only variant shared between the
      two Enterococcus spp.; however, distinct optrAWT loci were detected for E.
      faecium and E. faecalis. Generally, optrA localized to a plethora of genetic
      backgrounds that differed even for identical optrA variants. This suggests
      transmission of a mobile genetic element harbouring the resistance locus.
      Additionally, identical optrA variants detected on presumably identical plasmids,
      that were present in unrelated strains, indicates dissemination of the entire
      optrA-containing plasmid. In accordance, in vitro conjugation experiments
      verified transfer of optrA plasmids between enterococci of the same and of
      different species. In conclusion, multiple optrA variants located on distinct
      plasmids and mobile genetic elements with the potential for conjugative transfer
      are supposedly causative for the emergence of optrA-positive enterococci. Hence,
      rapid dissemination of the resistance determinant under selective pressure
      imposed by extensive use of last-resort antibiotics in clinical settings could be
      expected.

PMID- 30236953
TI  - Predicting antibiotic combination effects on the selection of resistant
      Staphylococcus aureus: In vitro model studies with linezolid and gentamicin.
AB  - To explore whether combinations of linezolid with gentamicin restrict
      Staphylococcus aureus resistance, the enrichment of resistant mutants was studied
      in an in vitro dynamic model. A clinical isolate S. aureus 10 and its linezolid
      resistant mutant selected by passaging on antibiotic-containing media were used
      in the study. The minimum inhibitory concentration (MIC) and the mutant
      prevention concentration (MPC) of antibiotics in combination were determined at a
      linezolid-to-gentamicin concentration ratio corresponding to the ratio of 24-h
      areas under the concentration-time curve (AUC24s) used in the pharmacokinetic
      simulations. Five-day treatments of S. aureus 10 supplemented with linezolid
      resistant mutants (mutation frequency 10-8) with twice-daily linezolid and once
      daily gentamicin, alone and in combination, were simulated at therapeutic and
      subtherapeutic AUC24s. Numbers of linezolid-resistant mutants increased at both
      therapeutic and subtherapeutic AUC24s, whereas gentamicin-resistant mutants were
      enriched only at the subtherapeutic AUC24 in single drug treatments. Linezolid
      gentamicin combinations prevented the enrichment of linezolid-resistant S. aureus
      and restricted the enrichment of gentamicin-resistant mutants. The pronounced
      anti-mutant effect of the combinations was attributed to lengthening the time
      above MPC of both linezolid and gentamicin as their MPCs were lowered. Unlike
      resistant S. aureus, killing of the total bacterial burden exposed to linezolid
      gentamicin combinations was less than in treatments with gentamicin alone, but
      greater than with linezolid alone. These findings indicate that (1) the anti
      mutant effects of antibiotic combinations can be predicted by MPC determinations
      at pharmacokinetically-derived concentration ratios, and (2) a given antibiotic
      combination may be optimal against resistant but not susceptible subpopulations.

PMID- 30236954
TI  - Bacteriophage therapy as an alternative treatment for human infections. A
      comprehensive review.
AB  - Bacteriophages, or phages, are viruses that infect bacteria. They were discovered
      around a century ago and have been used ever since for therapeutic purposes,
      particularly in former Soviet Union countries. Their use in Western countries was
      abandoned after the discovery and broad use of penicillin. The rising problem of
      antimicrobial resistance has revived interest in bacteriophage therapy. The aim
      of this article is to provide a comprehensive review of all aspects of natural
      phage therapy.

PMID- 30236956
TI  - Active monotherapy and combination therapy for extensively drug-resistant
      Pseudomonas aeruginosa pneumonia.
AB  - Data on treatment regimens and outcomes of extensively drug-resistant Pseudomonas
      aeruginosa (XDR-PA) pneumonia are currently limited. A 6-year retrospective
      cohort study of adult patients diagnosed with XDR-PA pneumonia was conducted
      between January 2011 and December 2016. All XDR-PA isolates were susceptible to
      colistin and/or fosfomycin alone. Some XDR-PA isolates, which had minimum
      inhibitory concentrations for doripenem of 4 or 8 mg/L, were considered to be
      susceptible to 4-h prolonged infusion therapy with high-dose doripenem. Definite
      treatment regimens were categorized into three groups: inactive therapy, active
      monotherapy and active combined two-drug therapy. Outcomes were compared between
      the three groups. In total, 136 patients were included, and 37% had ventilator
      associated pneumonia. Twenty-two, 74 and 40 patients received inactive therapy,
      active monotherapy and active combined two-drug therapy, respectively.
      Demographic and clinical characteristics were comparable between the three
      groups. Rates of 28-day survival and microbiological cure were significantly
      higher in patients who received active combined two-drug therapy compared with
      those who received active monotherapy and inactive therapy [90% vs 51% vs 0%
      (P<0.001) and 90% vs 54% vs 0% (P<0.001), respectively]. Kaplan-Meier survival
      analysis demonstrated a survival benefit of those who received active combined
      two-drug therapy over those who received active monotherapy and inactive therapy.
      Predictors for 28-day mortality were no infectious diseases (ID) consultations
      [adjusted odds ratio (aOR) 10.93; P<0.001], and receipt of inactive therapy (aOR
      42.07; P<0.001) or active monotherapy (aOR 6.63; P=0.002) compared with receipt
      of active combined two-drug therapy. Active combined two-drug therapy was
      associated with better survival compared with active monotherapy for XDR-PA
      pneumonia. ID consultation was associated with a reduction in mortality.

PMID- 30236955
TI  - Bacteriophage Sb-1 enhances antibiotic activity against biofilm, degrades
      exopolysaccharide matrix and targets persisters of Staphylococcus aureus.
AB  - Most antibiotics have limited or no activity against bacterial biofilms, whereas
      bacteriophages can eradicate biofilms. We evaluated whether Staphylococcus aureus
      specific bacteriophage Sb-1 could eradicate biofilm, both alone and in
      combination with different classes of antibiotics, degrade the extracellular
      matrix and target persister cells. Biofilm of methicillin-resistant S. aureus
      (MRSA) ATCC 43300 was treated with Sb-1 alone or in (simultaneous or staggered)
      combination with fosfomycin, rifampin, vancomycin, daptomycin or ciprofloxacin.
      The matrix was visualized by confocal fluorescent microscopy. Persister cells
      were treated with 104 and 107 plaque-forming units (PFU)/mL Sb-1 for 3 h in
      phosphate-buffered saline (PBS), followed by colony-forming units (CFU) counting.
      Alternatively, bacteria were washed and incubated in fresh brain heart infusion
      (BHI) medium and bacterial growth assessed after a further 24 h. Pretreatment
      with Sb-1 followed by the administration of subinhibitory concentrations of
      antibiotic caused a synergistic effect in eradicating MRSA biofilm. Sb-1
      determined a dose-dependent reduction of matrix exopolysaccharide. Sb-1 at 107
      PFU/mL showed direct killing activity on ~ 5 * 105 CFU/mL persisters. However,
      even a lower titer had lytic activity when phage-treated persister cells were
      inoculated in fresh medium, reverting to a normal-growing phenotype. This study
      provides valuable data on the enhancing effect of Sb-1 on antibiotic efficacy,
      exhibiting specific antibiofilm features. Sb-1 can degrade the MRSA
      polysaccharide matrix and target persister cells and is therefore suitable for
      treatment of biofilm-associated infections.

PMID- 30236957
TI  - Incidence and Risk Factors for Acquisition of Extended-Spectrum beta-Lactamase
      Producing Enterobacteriaceae in Newborns in Seville, Spain: A Prospective Cohort
      Study.
AB  - BACKGROUND: ESBL-producing Enterobacteriaceae (ESBL-E) are an emerging cause of
      infections in children. Data are scarce on incidence rates and risk factors for
      acquisition of colonisation with ESBL-E. METHODS: A total of 46 and 50 newborns
      from colonised and non-colonised mothers, respectively, were followed during one
      year after birth. Rectal swabs were performed every 3 months to detect ESBL-E;
      blaESBL were characterised and isolates were typed for comparison. Multivariate
      analysis for risk factors was performed using Cox regression. RESULTS: Incidence
      density of any new acquisition and of first acquisition of ESBL-E was 2.7 and 1.9
      episodes per 100 children-month, respectively, among children whose mothers were
      colonised, and 1.2 and 1.3, respectively, among children whose mothers were not.
      The weighted average prevalence of colonisation rates during the first year were
      15.9% and 8%, respectively. No infections due to ESBL-E were detected. Living
      with pets at home, breastfeeding, sterilisation of feeding bottles and out-of
      home childcare were protective for ESBL-E acquisition; having a colonised mother
      increased the risk. The most frequent ESBL types were CTX-M-14 and CTX-M-1. In
      5/19 (26.3%) children with acquisition of new clones, the acquired ESBL-E was
      shared with their mothers. CONCLUSIONS: Acquisition of ESBL-E colonisation is not
      rare during the first year of life. Breastfeeding and out-of-home childcare were
      protective for acquisition, and colonised mothers were associated with increased
      risk. However, the same clone was shared by mother and child in only a subset of
      acquisition episodes.

PMID- 30236958
TI  - Synergistic and bactericidal activities of mecillinam, amoxicillin and clavulanic
      acid combinations against ESBL-producing Escherichia coli in 24-h time-kill
      experiments.
AB  - This study aimed to evaluate the potential synergistic and bactericidal effects
      of mecillinam in combinations with amoxicillin and clavulanic acid against ESBL
      producing Escherichia coli. Eight clinical isolates with varying susceptibility
      to mecillinam (MICs 0.125 to >256 mg/L) and high-level resistance to amoxicillin
      (MICs >256 mg/L) were used. Whole genome sequencing was performed to determine
      the presence of beta-lactamase genes and cysB gene mutations. The activity of the
      single drugs and combinations of two or three drugs was tested in 24-h time-kill
      experiments. Population analysis was performed for two strains before and after
      experiments. Only one strain had a mutation in the cysB gene resulting in an
      amino acid substitution. With the two-drug combinations, initial killing was
      observed with both mecillinam and amoxicillin when combined with clavulanic acid.
      Synergy was observed with mecillinam and clavulanic acid against one strain and
      with amoxicillin and clavulanic acid against three strains. However, following
      significant regrowth, a bactericidal effect was found only with amoxicillin and
      clavulanic acid against two strains. Pre-existing subpopulations with elevated
      mecillinam MICs were detected before experiments and were selected with
      mecillinam alone or in two-drug combinations. In contrast, the three-drug
      combination showed enhanced activity with synergy against six strains, a
      bactericidal effect against all eight strains and suppression of resistance
      during 24 h antibiotic exposure. This combination may be of clinical interest in
      treatment of urinary tract infections caused by ESBL-producing E. coli.

PMID- 30236959
TI  - Net emergence of substitutions at position 28 in NS5A of hepatitis C virus
      genotype 4 in patients failing direct-acting antivirals detected by next
      generation sequencing.
AB  - More data on resistance of HCV genotype (GT) 3 and 4 to direct-acting antivirals
      (DAAs) are still needed. Here we investigated the presence of resistance
      associated substitutions (RASs) pre- and post-treatment and their emergence under
      DAAs in HCV GT3- and GT4-infected patients failing DAA regimens by next
      generation sequencing (NGS). Sanger sequencing and NGS were performed on NS5B and
      NS5A in plasma samples prior to and post treatment of 13 patients. Positions
      implicated in resistance to anti-NS5A and anti-NS5B in the literature were
      analysed. No baseline RASs was detected in NS5B but one GT4r virus developed the
      mutation S282T at failure. In NS5A, pre-existing RASs or polymorphisms were
      detected in viruses of 6/10 patients (L28M for a GT4a, M28V for a GT4r, L30R for
      a GT4a, 2 GT4d and 1 GT4r, and T58P for a GT4d) by Sanger sequencing and in
      viruses of 7/10 patients by NGS. Additional baseline minority substitutions
      detected by NGS were Y93H in a GT3a, L28M in a GT4a and GT4d, and L28F in a GT4d
      virus. At failure, these substitutions were found at a frequency of 100%. Y93H
      was detected alone at baseline, whilst L28M and L28F were accompanied by
      polymorphisms L30R or L30R + T58P. Use of NGS in patients failing DAAs and
      infected by HCV GT3 and GT4 revealed the emergence of specific patterns of
      substitutions in NS5A and NS5B, in particular substitutions at position 28 in
      NS5A in GT4 virus, highlighting the need to list these substitutions in
      guidelines for resistance interpretation.

PMID- 30236961
TI  - Evaluation of Response to Enzalutamide Consecutively After Abiraterone
      Acetate/Prednisone Failure in Patients With Metastatic Castration-resistant
      Prostate Cancer.
AB  - INTRODUCTION: Treatment of metastatic castration-resistant prostate cancer
      (mCRPC) has evolved significantly during the past decade, and the preferred
      combination and/or sequence of these treatments remains controversial. In this
      retrospective study, we explored clinical and pathologic factors that could
      predict response to consecutive treatment with enzalutamide (ENZA) after disease
      progression (PD) on abiraterone acetate and prednisone (AA/P). PATIENTS AND
      METHODS: Data were collected from 40 consecutive patients with mCRPC who were
      treated with ENZA without other interim therapy after progression on AA/P.
      RESULTS: The median time from prostate cancer initial diagnosis to AA/P treatment
      was 6.2 (range, 0.9-16.3) years. The median prostate-specific antigen (PSA)
      progression-free survival (PSA-PFS) from treatment initiation was 8.5 months (95%
      confidence interval [CI], 7.1-10.1 months) and 2.3 months (95% CI, 1.8-3.4
      months) on AA/P and ENZA, respectively. The median time to PD from treatment
      initiation was 9.7 months (95% CI, 7.1-12.4 months) and 3 months (95% CI, 2.3-4.1
      months) on AA/P and ENZA, respectively. The correlations were weak between the
      best percent change in PSA on ENZA and time from diagnosis to AA/P initiation,
      best absolute or percentage change in PSA on AA/P, time to PSA progression or PD
      on AA/P. Patients with longer than the median duration of treatment with AA/P
      (11.73 months) had longer PSA-PFS on ENZA (median 2.8 vs. 1.9 months; P = .035).
      CONCLUSIONS: In this retrospective analysis, we did not find any clinical or
      pathologic factors associated with response to ENZA administered consecutively
      after AA/P. Patients with longer than median AA/P treatment duration had longer
      PSA-PFS on ENZA. Further evaluations and validation are greatly needed.

PMID- 30236960
TI  - The intrinsic resistome of Klebsiella pneumoniae.
AB  - Molecular epidemiology studies aiming at understanding the acquisition of
      antimicrobial resistance by clinical isolates of Klebsiella pneumoniae are
      regularly published; however, information on the genes that contribute to its
      characteristic phenotype of resistance to antibiotics (intrinsic resistome) is
      scarce. To fill this gap, a K. pneumoniae transposon mutant library was screened
      and 171 mutants presenting changes in their susceptibility to antibiotics were
      selected, in which the transposon insertion site was determined in 75. Twenty
      seven mutants for which insertion points had been previously identified were
      included in the analysis. A total of 102 mutants were selected for further
      studies. In 70 mutants the transposon was inserted in a gene with a known
      function, whilst in 19 the insertion occurred in genes encoding proteins with
      unknown functions and 13 insertions occurred in intergenic regions. Moreover, 87
      of the insertions were localised in the chromosome, with 15 insertions located in
      the two plasmids carried by this strain. Whereas some of the mutated genes are
      already known to be involved in antimicrobial resistance (ampG, acrB, tolC),
      several of them are involved in regular processes of bacterial physiology,
      including K. pneumoniae virulence. Together with results published for other
      organisms, these results support that determinants involved in basic processes of
      bacterial physiology may contribute to antimicrobial resistance. These findings
      also indicate that, besides acquired resistance genes, plasmids may harbour other
      genes belonging to their backbone that can also be involved in resistance.

PMID- 30236962
TI  - Hippocampal NPY Y2 receptors modulate memory depending on emotional valence and
      time.
AB  - Posttraumatic stress disorder is characterized by contextually inappropriate, dys
      regulated and generalized fear expression and often resistant to therapy. The
      hippocampus integrates contextual information into spatial and emotional
      memories, but how diverse modulatory neurotransmitters are shaping this process
      is not known. Neuropeptide Y is a peptide-neurotransmitter, which modulates
      hippocampal excitability by activating several G-protein-coupled receptors.
      Postsynaptic Y1 receptors create strong anxiolytic and fear-suppressing behavior,
      while pre-synaptic Y2 receptors (Y2R) are mainly anxiogenic. The role of Y2Rs in
      spatial compared to emotional learning is, however, still controversial. Here we
      show that deletion of Y2Rs increased recall, but delayed extinction of contextual
      fear. Interestingly, spatial memory in the Barnes maze was enhanced during early
      and late testing, suggesting that Y2Rs suppress learning by hippocampal and extra
      hippocampal mechanisms. To demonstrate sufficiency of hippocampal Y2Rs we
      performed viral vector-mediated, locally restricted re-expression of Y2Rs in the
      hippocampus of Y2KO mice. This treatment reduced spatial memory to the level of
      wildtype mice only during early, but not late recall. Furthermore, contextual
      fear was reduced, while induction of fear extinction appeared earlier. Our
      results suggest that hippocampal Y2R signaling inhibits learning in a time- and
      content-specific way, resulting in an early reduction of spatial memory and in a
      specific suppression of fear, by reducing fear recall and promoting fear
      extinction. We thus propose that reduction of hippocampal excitability through
      pre-synaptic Y2Rs may control the integration of contextual information into
      developing memories.

PMID- 30236963
TI  - Neurotherapeutic capacity of P7C3 agents for the treatment of Traumatic Brain
      Injury.
AB  - Traumatic brain injury (TBI) is a significant public health problem around the
      world. A promising area of research is the characterization of small, drug-like
      molecules that have potent clinical properties. One pharmacotherapeutic agent in
      particular, an aminopropyl carbazole called P7C3, was discovered using an in vivo
      screen to identify new agents that augmented the net magnitude of adult
      hippocampal neurogenesis. P7C3 greatly enhanced neurogenesis by virtue of
      increasing survival rates of immature neurons. The potent neuroprotective
      efficacy of P7C3 is likely due to enhanced nicotinamide phosphoribosyltransferase
      (NAMPT) activity, which supports critical cellular processes. The scaffold of
      P7C3 was found to have favorable pharmacokinetic properties, good
      bioavailability, and was nontoxic. Preclinical studies have shown that
      administration of the P7C3-series of neuroprotective compounds after TBI can
      rescue and reverse detrimental cellular events leading to improved functional
      recovery. In several TBI models and across multiple species, P7C3 and its
      analogues have produced significant neuroprotection, axonal preservation, robust
      increases in the net magnitude of adult neurogenesis, protection from injury
      induced LTP deficits, and improvement in neurological functioning. This review
      will elucidate the exciting and diverse therapeutic findings of P7C3
      administration in the presence of a complex and multifactorial set of cellular
      and molecular challenges brought forth by experimental TBI. The clinical
      potential and broad therapeutic applicability of P7C3 warrants much needed
      investigation into whether these remedial effects can be replicated in the
      clinic. P7C3 may serve as an important step forward in the design, understanding,
      and implementation of pharmacotherapies for treating patients with TBI.

PMID- 30236964
TI  - Dissociated features of social cognition altered in mouse models of
      schizophrenia: Focus on social dominance and acoustic communication.
AB  - Social and communication impairments are common features of psychiatric
      disorders. Animal models of schizophrenia display various social deficits due to
      difference in tests, mouse strains and drugs. Moreover, communication deficits
      have not been studied. Our objectives were to assess and compare three major
      features of social cognition in different mouse models of schizophrenia: interest
      for a social stimulus, organization and acceptance of social contact, and
      acoustic communication to question whether mouse models for schizophrenia with
      social dysfunction also exhibit vocal communication defects. To achieve these
      aims we treated acutely C57BL/6J mice either with MK-801 or ketamine and tested
      WT and microtubule-associated protein 6 -MAP6- KO mice in two complementary
      social tasks: the 3-chamber test which measures social motivation and the social
      interaction task -SIT- which relies on prefrontal cortex activity and measures
      the ability to organize and respond to a real interaction, and which promotes
      ultrasonic vocalizations. Our results reveal that schizophrenia models have
      intact interest for a social stimulus in the 3-chamber test. However, thanks to
      principal component analyses of social interaction data, we demonstrate that
      social motivation and the ability to act socially rely on distinct mechanisms in
      revealing a decrease in dominance and communication in pharmacological
      schizophrenia models along with social withdraw, classically observed in
      schizophrenia, in MK-801 model. In this latter model, some social parameters can
      be significantly improved by aripiprazole, an atypical antipsychotic. Our social
      protocol, combined with fine-tuned analysis, is expected to provide an innovative
      framework for testing future treatments in preclinical models.

PMID- 30236965
TI  - Human Factors and Ergonomics in Sport and Outdoor Recreation: From individuals
      and their equipment to complex sociotechnical systems and their frailties.

PMID- 30236967
TI  - Orbital wooden foreign body manifesting as hyperdensity on computed tomography.
AB  - Detection of wooden foreign bodies within the orbit can be difficult on imaging,
      including computed tomography (CT). When visible, wood appears iso- or hypodense
      and can mimic air or fat. We report the case of a 3-year-old boy with progressive
      orbital cellulitis following a penetrating wood injury to the right lower lid. CT
      imaging revealed a linear hyperdensity contiguous with an orbital abscess. He
      underwent a right anterior orbitotomy with abscess drainage, during which
      exploration revealed a 2.3 cm retained wooden foreign body. The appearance of
      wood as hyperdense on imaging is unusual. In the appropriate context, high
      clinical suspicion for retained wood should be maintained with any irregularity
      on CT imaging.

PMID- 30236966
TI  - Consecutive superior oblique palsy after adjustable suture spacer surgery for
      Brown syndrome: incidence and predicting risk.
AB  - PURPOSE: To determine the incidence of and to identify characteristics predicting
      significant superior oblique palsy (SOP) after adjustable superior oblique suture
      spacer surgery for treatment of Brown syndrome. METHODS: The medical records of
      patients treated for unilateral Brown syndrome with adjustable suture spacers
      (2005-2016) were reviewed to identify possible association of age at surgery,
      spacer length, surgeon performing procedure, severity of Brown syndrome,
      preoperative hypotropia in primary position and affected side gaze, and reduction
      in Brown restriction on postoperative superior oblique function. "Good"
      postoperative superior oblique function was defined as absence of hypertropia and
      diplopia in primary position and no more than intermittent diplopia in downgaze
      comfortably fused with <=4Delta base-down or head tilt of <10 degrees . Presence
      of postoperative hypertropia in primary position with increase in downgaze met
      criteria for significant SOP. Postoperative Brown restriction of <= -2 indicated
      resolution of Brown syndrome. RESULTS: Median age at surgery was 59 months,
      interquartile range (IQR) was 32-82 months, and median spacer length was 6 mm
      (range, 2-7 mm) for 19 included patients. Preoperative median hypotropia was
      9Delta (IQR, 0Delta-12Delta) in primary position and 18Delta (IQR, 5Delta
      22Delta) in affected side gaze. Of 19 patients, 16 (84%) achieved sufficient
      resolution of Brown syndrome, but 6 (32%) developed significant SOP. Modest
      preoperative hypotropia in affected side gaze was the only predictor of
      significant SOP (likelihood ratio test = 7.11; P = 0.008). Logistic regression
      modeling enabled estimation of risk of significant SOP based on preoperative side
      gaze hypotropia. CONCLUSIONS: Suture spacer surgery can result in significant
      SOP. Risk may be predicted by magnitude of preoperative side gaze hypotropia.

PMID- 30236968
TI  - Multi-segmental spine image registration supporting image-guided interventions of
      spinal metastases.
AB  - BACKGROUND: Radiofrequency ablation was introduced recently to treat spinal
      metastases, which are among the most common metastases. These minimally-invasive
      interventions are most often image-guided by flat-panel CT scans, withholding
      soft tissue contrast like MR imaging. Image fusion of diagnostic MR and operative
      CT images could provide important and useful information during interventions.
      METHOD: Diagnostic MR and interventional flat-panel CT scans of 19 patients, who
      underwent radiofrequency ablations of spinal metastases were obtained. Our
      presented approach piecewise rigidly registers single vertebrae using normalized
      gradient fields and embeds them within a fused image. Registration accuracy was
      determined via Euclidean distances between corresponding landmark pairs of ground
      truth data. RESULTS: Our method resulted in an average registration error of
      2.35mm. An optimal image fusion performed by landmark registrations achieved an
      average registration error of 1.70mm. Additionally, intra- and inter-reader
      variability was determined, resulting in mean distances of corresponding landmark
      pairs of 1.05mm (MRI) and 1.03mm (flat-panel CT) for the intra-reader variability
      and 1.36mm and 1.28mm for the inter-reader variability, respectively.
      CONCLUSIONS: Our multi-segmental approach with normalized gradient fields as
      image similarity measure can handle spine deformations due to patient positioning
      and avoid time-consuming manually performed registration. Thus, our method can
      provide practical and applicable intervention support without significantly
      delaying the clinical workflow or additional workload.

PMID- 30236969
TI  - Asymptomatic uterine torsion diagnosed after two uneventful pregnancies.

PMID- 30236970
TI  - Photoperiodic regulation of plasma gonadotropin levels in previtellogenic greater
      amberjack (Seriola dumerili).
AB  - In Seriola species, exposure to a long photoperiod regime is known to induce
      ovarian development. This study examined photoperiodic effects on pituitary gene
      expression and plasma levels of follicle-stimulating hormone (Fsh) and
      luteinizing hormone (Lh) in previtellogenic greater amberjack (Seriola dumerili).
      The fish were exposed to short (8L:16D) or long (18L:6D) photoperiod. The water
      temperature was maintained at 22  degrees C. Compared with the short-photoperiod
      group, plasma Fsh levels were higher on days 10 and 30 in the long-photoperiod
      group, but plasma Lh levels did not significantly differ. On day 30, pituitary
      Fsh- and Lh-beta subunit gene expressions were also higher in the long
      photoperiod group than the short-photoperiod group, whereas alpha-subunit gene
      expressions were higher on days 20 and 30. Throughout the experiment, average
      gonadosomatic index and plasma E2 levels did not significantly differ between the
      two groups. This study clearly demonstrated that a long photoperiod induced Fsh
      release in the previtellogenic fish followed by upregulation of pituitary Fsh and
      Lh subunit gene expressions. An increase in plasma Fsh levels may be a key factor
      that mediates the photoperiodic effect on the initiation of ovarian development.

PMID- 30236971
TI  - Discussing death: Making end of life implicit or explicit in paediatric
      palliative care consultations.
AB  - OBJECTIVE: To consider whether and how family members and clinicians discuss end
      of life during paediatric palliative care consultations. METHODS: Nine naturally
      occurring paediatric palliative care consultations were video recorded and
      analysed using conversation analytic methods. ANALYSIS: Focusing on three
      consultations in which end of life was treated as a certain outcome, analysis
      explored ways in which end of life was made either implicit or explicit within
      these consultations. Our analysis suggests that end of life was made explicit
      when: 1) ancillary to the current focus of discussion, 2) in relation to someone
      else's child, or 3) specifically relevant to the local context of the discussion.
      More commonly, in all other instances in the data, end of life was made implicit
      during discussions relating to this matter. CONCLUSION: This preliminary research
      indicates that the local context of a conversation can influence how end of life
      is mentioned and discussed. PRACTICE IMPLICATIONS: Clinicians often are
      encouraged to promote honest and 'open' discussions about end of life. Our
      findings show that it is not necessary to explicitly mention end of life in order
      to discuss it.

PMID- 30236973
TI  - Effect of matrix metalloproteinase 8 inhibitor and chlorhexidine on the
      cytotoxicity, oxidative stress and cytokine level of MDPC-23.
AB  - OBJECTIVE: This study investigated the effect of matrix metalloproteinase-8
      inhibitor I (MMP8-I) and chlorhexidine (CHX) on the viability, oxidative stress
      and cytokine secretion of MDPC-23 under short-term (30min) and long-term (3 days)
      culture. METHODS: MDPC-23 were treated with MMP8-I or CHX for 30min, 1day, 2days
      and 3days to detect the proliferation by 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyl tetrazolium bromide (MTT) assay. In the following assays, MDPC-23
      treated with 0.0003% CHX were referred to CHX group, treated with 8MUM MMP8-I
      were MMP8-I group. Cells without additional treatment were regarded as control
      group. The cell cycle, reactive oxygen species (ROS) level, and apoptosis were
      assessed by flow cytometry. The cytokine level was quantified by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: In 30min, CHX at concentrations higher than
      0.0003% dilution inhibited cell proliferation when compared to the control group.
      MMP8-I (0.1-500MUM) showed no obvious cytotoxicity to MDPC-23, and MMP8-I
      (1000MUM) inhibited cell proliferation. In 3 days, CHX (0.0003%) significantly
      inhibited cell growth, while MMP8-I (8MUM) had no cytotoxicity. In the CHX group,
      the S phase population was decreased, and cellular ROS were increased in 3 days.
      In the MMP8-I group, the change of S phase population and cellular ROS was not
      significant compared with the control group. Cell apoptosis was not elevated in
      the MMP8-I group, while the apoptosis rate was increased in the CHX group both in
      30min and 3 days. In 30min, CHX treatment significantly increased the secretion
      of interleukin (IL)-1beta and IL-8, but slightly increased the secretion of IL
      10, while MMP8-I caused no change in cytokines. In 3 days, CHX treatment
      significantly increased the secretion of IL-1beta, IL-6, and IL-8, and inhibited
      the secretion of IL-10. MMP8-I treatment caused the increase of IL-6.
      SIGNIFICANCE: Compared with CHX, MMP8-I at low concentration did not result in
      cytotoxicity, oxidative stress, or the disorder of immune response.

PMID- 30236972
TI  - Glutamatergic Projections to the Cochlear Nucleus are Redistributed in Tinnitus.
AB  - Tinnitus alters auditory-somatosensory plasticity in the cochlear nucleus (CN).
      Correspondingly, bimodal auditory-somatosensory stimulation treatment attenuates
      tinnitus, both in animals and humans (Marks et al., 2018). Therefore, we
      hypothesized that tinnitus is associated with altered somatosensory innervation
      of the CN. Here, we studied the expression of vesicular glutamate transporters 1
      and 2 (VGLUT1 and VGLUT2) in the CN, which reveals glutamatergic projections from
      the cochlea as well as somatosensory systems to this brainstem auditory center.
      Guinea pigs were unilaterally exposed to narrowband noise and behaviorally tested
      for tinnitus using gap-prepulse inhibition of the acoustic startle. Following
      physiological and behavioral measures, brain sections were immunohistochemically
      stained for VGLUT1 or VGLUT2. Puncta density was determined for each region of
      the ipsilateral and contralateral CN. Tinnitus was associated with an ipsilateral
      upregulation of VGLUT2 puncta density in the granule cell domain (GCD) and
      anteroventral CN (AVCN). Furthermore, there was a tinnitus-associated interaural
      asymmetry for VGLUT1 expression in the AVCN and deep layer of the dorsal CN
      (DCN3), due to contralateral downregulation of VGLUT1 expression. These tinnitus
      related glutamatergic imbalances were reversed upon bimodal stimulation
      treatment. Tinnitus-associated ipsilateral upregulation of VGLUT2-positive
      projections likely derives from somatosensory projections to the GCD and AVCN.
      This upregulation may underlie the neurophysiological hallmarks of tinnitus in
      the CN. Reversing the increased ipsilateral glutamatergic innervation in the CN
      is likely a key mechanism in treating tinnitus.

PMID- 30236974
TI  - Simulation study of the effects of buildings, trees and paved surfaces on ambient
      dose equivalent rates outdoors at three suburban sites near Fukushima Dai-ichi.
AB  - The influence of buildings, trees and paved surfaces on outdoor ambient dose
      equivalent rates (H*(10)) in suburban areas near to the Fukushima Dai-ichi
      Nuclear Power Plant (FDNPP) was investigated with Monte Carlo simulations.
      Simulation models of three un-decontaminated sites in Okuma and Tomioka were
      created with representations of individual buildings, trees and roads created
      using geographic information system (GIS) data. The 134Cs and 137Cs radioactivity
      distribution within each model was set using in-situ gamma spectroscopy
      measurements from December 2014 and literature values for the relative
      radioactive cesium concentration on paved surfaces, unpaved land, building outer
      surfaces, forest litter and soil layers, and different tree compartments.
      Reasonable correlation was obtained between the simulations and measurements for
      H*(10) across the sites taken in January 2015. The effect of buildings and trees
      on H*(10) was investigated by performing simulations removing these objects, and
      their associated 134Cs and 137Cs inventory, from the models. H*(10) were on
      average 5.0% higher in the simulations without buildings and trees, even though
      the total 134Cs and 137Cs inventory within each model was slightly lower. The
      simulations without buildings and trees were then modified to include 134Cs and
      137Cs in the ground beneath locations where buildings exist in reality, and the
      inventory of paved surfaces modelled as if they had high retention of 134Cs and
      137Cs fallout like soil areas. H*(10) increased more markedly in these cases than
      when considering the shielding effect of buildings and trees alone. These results
      help clarify the magnitude of the effect of buildings, trees and paved surfaces
      on H*(10) at the un-decontaminated sites within Fukushima Prefecture.

PMID- 30236975
TI  - Six-year monitoring study of radiocesium transfer in forest environments
      following the Fukushima nuclear power plant accident.
AB  - The study investigated temporal changes in the 137Cs concentrations in vegetal
      and hydrological samples collected from various forests in Yamakiya District,
      Kawamata Town of Fukushima prefecture over six years following the Fukushima Dai
      ichi nuclear power plant accident. Cesium-137 was detected in all forest
      environmental samples. However, the concentration in most samples decreased
      exponentially with time. The 137Cs concentrations in throughfall samples
      exhibited a double-exponential decreasing trend with time. Temporal changes in
      the 137Cs concentration in vegetal samples and stemflow were approximated by
      using a single-exponential equation. A comparison of the decline coefficient for
      the latter observation period (>2 y since the accident) revealed that the
      declining trend of 137Cs concentrations varied between foliage and the outer
      barks of the Japanese cedar and Japanese konara oak trees. The 137Cs
      concentration in cedar needles decreased exponentially while that in konara oak
      leaves was constant over the last six years. Conversely, the declining trend of
      137Cs concentration in the outer bark of konara oak exceeded that of cedar. The
      results suggested that self-decontamination processes and internal recycling of
      137Cs varied among tree species and different tree parts. The results indicated
      that the leaching of 137Cs in the throughfall in Japanese cedar was dependent on
      the 137Cs concentration in needles. However, a comparison of 137Cs concentrations
      in vegetal and hydrological samples from each sampling year showed that the
      leaching rate decreased with time. Conversely, the 137Cs concentrations in the
      stemflow were independent of the concentrations in the outer bark. The declining
      trend of 137Cs concentrations in litterfall (lambda: 0.31-0.33 y-1) was similar
      to that of the mean of new/old needles (lambda: 0.26-0.33 y-1) for cedar stands.
      With respect to the hydrological components, the 137Cs concentration in the
      stemflow (lambda: 0.32-0.33 y-1) decreased at a slightly slower rate than that in
      the throughfall (lambda: 0.36-0.54 y-1) for the cedar forest. The decline
      coefficients of 137Cs concentration in the aforementioned types of hydrological
      components slightly exceeded that for the vegetal samples. The results suggest
      that monitoring of 137Cs concentrations in hydrological components and vegetal
      samples can aid in further understanding the leaching mechanisms of 137Cs from
      trees to rainwater.

PMID- 30236976
TI  - Biphasic analysis of rat brain slices under creep indentation shows nonlinear
      tension-compression behavior.
AB  - Biphasic theory can provide a mechanistic description of deformation and
      transport phenomena in soft tissues, and has been used to model surgery and drug
      delivery in the brain for decades. Knowledge of corresponding mechanical
      properties of the brain is needed to accurately predict tissue deformation and
      flow transport in these applications. Previously in our group, creep indentation
      tests were conducted for multiple anatomical regions in acute rat brain tissue
      slices. In the current study, a biphasic finite element model of creep
      indentation was developed with which to compare these data. Considering the soft
      tissue structure of brain, the solid matrix was assumed to be composed of a neo
      Hookean ground matrix reinforced by continuously distributed fibers that exhibits
      tension-compression nonlinearity during deformation. By fixing Poisson's ratio of
      the ground matrix, Young's modulus, fiber modulus and hydraulic permeability were
      estimated. Hydraulic permeability was found to be nearly independent of the
      properties of the solid matrix. Estimated modulus (40 Pa to 1.1 kPa for the
      ground matrix, 3.2-18.2 kPa for fibers) and hydraulic permeability (1.2-5.5*10
      13m4/N s) fell within an acceptable range compared with those in previous
      studies. Instantaneous indentation depth was dominated by tension provided by
      fibers, while the tissue response at equilibrium was sensitive to Poisson's
      ratio. Results of sensitivity analysis also point to the necessity of considering
      tension-compression nonlinearity in the solid phase when the biphasic material
      undergoes large creep deformation.

PMID- 30236977
TI  - The effect of pleural fluid layers on lung surface wave speed measurement:
      Experimental and numerical studies on a sponge lung phantom.
AB  - Pleural effusion manifests as compression of pleural fluid on the lung parenchyma
      contributing to hypoxemia. Medical procedures such as drainage of plural fluid
      releases this compression and increases oxygenation. However, the effect of
      pleural effusion on the elasticity of lung parenchyma is unknown. By using lung
      ultrasound surface wave elastography (LUSWE) and finite element method (FEM), the
      effect of pleural effusion on the elasticity of superficial lung parenchyma in
      terms of surface wave speed measurement was evaluated in a sponge phantom study.
      Different thicknesses of ultrasound transmission gel used to simulated pleural
      fluid were inserted into a condom, which was placed between the sponge and
      standoff pad. A mechanical shaker was used to generate vibration on the sponge
      phantom at different frequencies ranging from 100 to 300 Hz while the ultrasound
      transducer was used to capture the motion for measurement of surface wave speed
      of the sponge. FEM was conducted based on the experimental setup and numerically
      assessed the influence of pleural effusion on the surface wave speed of the
      sponge. We found from FEM experiments that the influence of thickness of
      ultrasound transmission gel was statistically insignificant on the surface wave
      speed of the sponge at 100 and 150 Hz.

PMID- 30236978
TI  - Braided bioresorbable cardiovascular stents mechanically reinforced by axial
      runners.
AB  - Polymeric bioresorbable stents (BRSs) can eliminate the long-term stent
      restenosis by degrading after vascular remolding and have been recommended for
      the congenital heart disease treatment. However, the mechanical weakness remains
      one of main inferiorities of their applications. So, the aim of this study was to
      develop mechanically reinforced bioresorbable stents (MRBSs) based on poly(p
      dioxanone) (PPDO) monofilaments and braiding technology. Axial runners were
      introduced and MRBSs showed greatly higher compression force and relatively lower
      viscous performance, as well as longer mechanical stability during degradation,
      compared with controls. Besides, stent compression behaviors were analyzed
      experimentally and numerically to investigate their deformation mechanisms. The
      results showed increased contacting points and friction force among yarns in
      MRBSs. Also, the skeleton formed in MRBSs attributed to higher yarn bending
      degree, strain energy and better structure stability during compression. Combined
      with the non-linear PPDO material stress-strain ratio and thermodynamic theory,
      yarn based stent compression modes were discussed. In addition, the autocatalysis
      and nonrandom chain scission degradation behaviors of MRBSs were revealed.

PMID- 30236979
TI  - Mechanical and structural analysis of the pulmonary valve in congenital heart
      defects: A presentation of two case studies.
AB  - OBJECTIVE: Congenital Heart Disease (CHD) is the leading cause of pediatric
      mortality, with many cases affecting the right ventricular outflow tract (RVOT)
      or pulmonary valve (PV). Understanding the mechanics of the disease condition can
      provide insight into development of durable repair techniques and bioengineered
      replacement devices. This work presents a mechanical and structural analysis of
      the pulmonary valve of two pediatric cases. METHODS: Two PV tissues were excised
      as part of the operative procedure. One PV was obtained from a 9-month-old with
      Noonan syndrome (Patient 1) and the other from a 6-month-old with tricuspid
      atresia (Patient 2). The leaflets were subjected to planar biaxial tensile
      testing and second harmonic generation (SHG) imaging for mechanical and
      structural evaluation. RESULTS AND DISCUSSION: Patient 1 exhibited a more
      anisotropic mechanical response than Patient 2, with sample stiffness on par with
      that of adult PV tissue. Additionally, both samples showed radial and
      circumferential alignment of collagen fibers on the ventricularis and fibrosa
      sides of the leaflets, respectively. Collagen fibers on the fibrosa side were
      also more crimped than on the ventricularis side.

PMID- 30236980
TI  - Ventricular arrhythmia and death among atrial fibrillation patients using anti
      arrhythmic drugs.
AB  - AIM: The aim of the study was to assess and compare the safety of antiarrhythmic
      drugs (AADs) in an unselected real-world population of patients with atrial
      fibrillation (AF). METHODS AND RESULTS: This is a study of all patients with
      diagnosed AF in the Swedish Patient register who filled a prescription for
      sotalol, amiodarone, dronedarone, flecainide or disopyramide during 2010 to 2015.
      The main end point consisted of arrhythmic death, successful resuscitation, new
      diagnosis of sustained ventricular tachycardia, ventricular fibrillation or
      implantation of ICD. All-cause mortality was a secondary end point. Minimum
      follow up was 1 year. Falsification end points were used to assess hidden
      confounding. 44,995 AF patients on AAD and 267,518 AF patients without AAD were
      studied during a total time at risk of over 1.1 million years. Compared to
      sotalol, the risk for the main end point was decreased with dronedarone (hazard
      ratio [HR] 0.58, 95% confidence interval [CI] 0.37-0.90), similar with flecainide
      (HR 0.95, 0.69-1.32) and disopyramide (HR 1.30, CI 0.83-2.05). All-cause
      mortality was lower with dronedarone (HR 0.44, CI 0.34-0.57) and flecainide (HR
      0.55, CI 0.44-0.68) than with sotalol. Hidden confounding prevented reliable
      assessment of amiodarone. CONCLUSIONS: Dronedarone was the only anti-arrhythmic
      drug with significantly lower risk for arrhythmic death, sustained ventricular
      arrhythmia or ICD implantation than sotalol among patients with atrial
      fibrillation. Both dronedarone and flecainide were associated with lower all
      cause mortality than sotalol.

PMID- 30236981
TI  - Regulation of membrane raft recruitment of the bradykinin B2 receptor by close
      association with the ATP/UTP receptor P2Y2.
AB  - Several G protein-coupled receptors are present in lipid rafts. We have shown
      that most of the P2Y2 receptor (P2Y2R) protein is fractionated into lipid rafts
      in COS 7 cells. In the same cells, about 25-30% of the bradykinin B2 receptor
      (B2R) protein is also fractionated into lipid rafts. When both P2Y2R and B2R are
      co-expressed, the distribution of P2Y2R remained unchanged, but more B2R shifted
      into the raft fraction. This indicates that the interaction between both
      receptors recruited B2R into the lipid rafts. After 15 min of UTP stimulation,
      both receptors almost completely disappeared from the cell surface by endocytosis
      as observed with a confocal fluorescence microscope. Furthermore, with bradykinin
      stimulation for 15 min, portions of both receptors disappeared from the cell
      surface and were endocytosed. As we reported previously with both CHO-K1 cells
      and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC
      resulted in the disappearance of both P2Y2R and B2R from the cell membrane
      surface. Thus, both P2Y2R and B2R migrate into membrane rafts and are endocytosed
      in parallel with signal crosstalk, clearly indicating that both closely interact
      on membrane rafts. The P2Y2R N-glycosylation deficient mutant does not migrate to
      the cell surface. It remains predominantly in the endoplasmic reticulum and is
      fractionated into raft fractions. In the presence of this glycosylation mutant,
      most of B2R remains in the endoplasmic reticulum, and is fractionated into the
      raft fraction. These findings demonstrate that in the membrane rafts of the
      endoplasmic reticulum, both receptors are already closely associated, and B2R
      shifts into the rafts by affinity with P2Y2R.

PMID- 30236982
TI  - Truncated dystrophin ameliorates the dystrophic phenotype of mdx mice by reducing
      sarcolipin-mediated SERCA inhibition.
AB  - Duchenne muscular dystrophy (DMD) and the less severe Becker muscular dystrophy
      (BMD) are due to mutations in the DMD gene. Previous reports show that in-frame
      deletion of exons 45-55 produces an internally shorted, but functional,
      dystrophin protein resulting in a very mild BMD phenotype. In order to elucidate
      the molecular mechanism leading to this phenotype, we generated exon 45-55
      deleted dystrophin transgenic/mdx (Tg/mdx) mice. Muscular function of Tg/mdx mice
      was restored close to that of wild type (WT) mice but the localization of the
      neuronal type of nitric oxide synthase was changed from the sarcolemma to the
      cytosol. This led to hyper-nitrosylation of the ryanodine receptor 1 causing
      increased Ca2+ release from the sarcoplasmic reticulum. On the other hand, Ca2+
      reuptake by the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) was
      restored to the level of WT mice, suggesting that the Ca2+ dysregulation had been
      compensated by SERCA activation. In line with this, expression of sarcolipin
      (SLN), a SERCA-inhibitory peptide, was upregulated in mdx mice, but strongly
      reduced in Tg/mdx mice. Furthermore, knockdown of SLN ameliorated the cytosolic
      Ca2+ homeostasis and the dystrophic phenotype in mdx mice. These findings suggest
      that SLN may be a novel target for DMD therapy.

PMID- 30236983
TI  - Interleukin-22 receptor 1 upregulation and activation in hypoxic endothelial
      cells improves perfusion recovery in experimental peripheral arterial disease.
AB  - OBJECTIVE: Inflammation induced by muscle ischemia is involved in tissue repair
      and perfusion recovery in peripheral arterial disease (PAD) patients. Interleukin
      (IL)-22 is an inflammatory cytokine discovered in recent years and shows
      versatile functions; however, its role in PAD remains unknown. Here, we test
      whether IL-22 and its receptors are involved in angiogenesis in experimental PAD.
      METHODS AND RESULTS: Both IL-22 and its receptor-IL-22 receptor 1(IL-22R1) were
      upregulated in muscle and endothelial cells after ischemia. In experimental PAD
      models, blocking IL-22 using IL-22 monoclonal antibody impaired perfusion
      recovery and angiogenesis; on the other hand, IL-22 treatment improved perfusion
      recovery. Ischemic muscle tissue was harvested 3 days after experimental PAD for
      biochemical test, IL-22 antagonism resulted in decreased Signal Transducer and
      Activator of Transcription (STAT3) phosphorylation, but did not alter the levels
      of VEGF-A or cyclic guanine monophosphate (cGMP) levels in ischemic muscle. In
      cultured endothelial cells, IL-22R1 was upregulated under simulated ischemic
      conditions, and IL-22 treatment increased STAT3 phosphorylation, endothelial cell
      survival and tube formation. Knock down of IL-22R1 or treatment with STAT3
      inhibitor blunted IL-22-induced endothelial cell survival or tube formation.
      CONCULSION: Ischemia-induced IL-22 and IL-22R1 upregulation improves angiogenesis
      in PAD by inducing STAT3 phosphorylation in endothelial cells. IL-22R1 may serve
      as a new therapeutic target for PAD.

PMID- 30236984
TI  - Hepatic conditional knockout of ATF6 exacerbates liver metabolic damage by
      repressing autophage through MTOR pathway.
AB  - The liver is a central metabolic organ. Activating transcription factor 6 (ATF6)
      acts as an ER stress responsive gene and is reported to attenuate hepatic
      steatosis. Over expressing a dominant-negative form of ATF6 exacerbates glucose
      intolerance and insulin resistance. In the present study, we used the conditional
      knockout technique to specifically knockout ATF6 in the mouse liver. We used qPCR
      to detect the mRNA levels of related genes. Western blot analysis was used to
      evaluate protein levels. Flow cytometry assay showed the apoptosis status.
      Glucose tolerance tests and insulin tolerance tests were used to determine
      glucose and insulin sensitivity. The results showed that liver specific knockout
      of ATF6 exacerbated HFD-induced hepatic steatosis and glucose tolerance.
      Abolished ATF6 exacerbated gluconeogenic metabolism by MTOR mediated down
      regulation of autophage. In conclusion, these findings suggest that therapeutic
      strategies by supplementing ATF6 may be beneficial for the treatment of glucose
      intolerance as well as insulin resistance in the high fat induced liver metabolic
      damage condition.

PMID- 30236985
TI  - Dynamic changes of proteasome and protective effect of bortezomib, a proteasome
      inhibitor, in mice with acute pancreatitis.
AB  - The proteasome is involved in the activation of NF-kappaB and can regulate the
      progression of inflammatory diseases. However, the role of proteasome in acute
      pancreatitis (AP) has not been demonstrated. In this study, we first observed
      that the protein level and activity of proteasome 20S were increased
      significantly in pancreatic injury tissues after caerulein-induced mild acute
      pancreatitis (MAP) induction, which was in consistent with the expression of the
      NF-kappaB nucleoprotein and positively correlated with the severity of AP. Then,
      bortezomib, a classical proteasome inhibitor, was used to intervene the
      progression of MAP in mice. The results showed that bortezomib administration
      reduced the serum amylase and lipase levels and mitigated histopathological
      manifestation of pancreatic injury in mice. Meanwhile, bortezomib decreased the
      expression of NF-kappaB p65 nucleoprotein as well as total proteasome 20S
      protein, and inhibited the activity of 20S in pancreatic tissues. In addition, we
      found that bortezomib could protect pancreatic acinar cell against necrosis and
      mitigate the severity of AP in a severe acute pancreatitis model induced by
      sodium taurocholate hydrate. Taken together, our study for the first time
      confirmed that the proteasome participated in the pathogenesis of AP and its
      inhibitor bortezomib could protect against AP in mice.

PMID- 30236986
TI  - SGIP1 dimerizes via intermolecular disulfide bond in MUHD domain during cellular
      endocytosis.
AB  - Along with its homologs FCHo1 and FCHo2, SGIP1 plays an important role in
      clathrin-mediated endocytosis. The highly conserved C-terminal MUHD domains in
      these proteins are the critical regions interacting with adapter molecules such
      as Eps15. The crystal structure of MUHD domain of SGIP1 has been reported
      previously. In this study, we found that MUHD domain of SGIP1 is capable of
      forming a stable dimer by an intermolecular disulfide bond formed by C632 in our
      crystal structure. The mutational study of C632 revealed that this residue is
      important for the function of SGIP1 during cellular endocytosis. Our study
      revealed a new dimerization and/or oligomerization manner in theses adaptor
      proteins, which is a critical prerequisite for their proper function.

PMID- 30236987
TI  - Modulation of lipid mediator profile may contribute to amelioration of chronic
      inflammation in adipose tissue of obese mice by pioglitazone.
AB  - Thiazolidinediones exert their antidiabetic effect in part by ameliorating
      chronic inflammation in adipose tissue. However, the precise mechanism of this
      anti-inflammatory action has remained unclear. We here investigated the effects
      of the TZD pioglitazone on the lipid mediator profile of adipose tissue in obese
      diabetic KKAy mice by metabololipidomics analysis based on liquid chromatography
      and tandem mass spectrometry. Pioglitazone treatment increased the amounts of pro
      resolving lipid mediators including lipoxin B4 (LXB4), resolvin E2, and
      eicosapentaenoic acid as well as reduced those of prostaglandin E2 and 4
      hydroxydocosahexaenoic acid in epididymal adipose tissue of KKAy mice. These
      effects were accompanied by increased expression of genes for the anti
      inflammatory proteins arginase 1, interleukin (IL)-13, and IL-10 in this tissue.
      Pioglitazone also increased LXB4 production in cultured 3T3-L1 adipocytes.
      Finally, LXB4 increased IL-10 gene expression in adipose tissue explants from
      KKAy mice. Together, our results suggest that up-regulation of LXB4 may
      contribute to the anti-inflammatory effect of pioglitazone in obese adipose
      tissue.

PMID- 30236989
TI  - Regulatory crosstalk between the oxidative stress-related transcription factor
      Nfe2l2/Nrf2 and mitochondria.
AB  - Mitochondria play essential roles in cellular bioenergetics, biosynthesis, and
      apoptosis. During the process of respiration and oxidative phosphorylation,
      mitochondria utilize oxygen to generate ATP, and at the same time, there is an
      inevitable generation of reactive oxygen species (ROS). As excess ROS create
      oxidative stress and damage cells, the proper function of the antioxidant defense
      system is critical for eukaryotic cell survival under aerobic conditions. Nuclear
      factor, erythroid 2-like 2 (Nfe2l2/Nrf2) is a master transcription factor for
      regulating basal as well as inducible expression of multiple antioxidant
      proteins. Nrf2 has been involved in maintaining mitochondrial redox homeostasis
      by providing reduced forms of glutathione (GSH); the reducing cofactor NADPH; and
      mitochondrial antioxidant enzymes such as GSH peroxidase 1, superoxide dismutase
      2, and peroxiredoxin 3/5. In addition, recent research advances suggest that Nrf2
      contributes to mitochondrial regulation through more divergent intermolecular
      linkages. Nrf2 has been positively associated with mitochondrial biogenesis
      through the direct upregulation of mitochondrial transcription factors and is
      involved in the mitochondrial quality control system through mitophagy
      activation. Moreover, several mitochondrial proteins participate in regulating
      Nrf2 to form a reciprocal regulatory loop between mitochondria and Nrf2.
      Additionally, Nrf2 modulation in cancer cells leads to changes in the
      mitochondrial respiration system and cancer bioenergetics that overall affect
      cancer metabolism. In this review, we describe recent experimental observations
      on the relationship between Nrf2 and mitochondria, and further discuss the
      effects of Nrf2 on cancer mitochondria and metabolism.

PMID- 30236988
TI  - NLRP3 inflammasome activation in liver cirrhotic patients.
AB  - AIMS: NLRP3 inflammasome activation is involved in the mechanism of liver
      cirrhosis. In this study, we investigated the levels of plasma IL-1beta and IL-18
      and their relationship to component traits in patients with liver cirrhosis, and
      NLRP3 inflammasome expression in liver of patients with liver cirrhosis. METHODS:
      A total of 75 patients with liver cirrhosis and 41 age-matched healthy control
      subjects were enrolled in this study. NLRP3 inflammasome expression and
      activation were measured in liver of patients with liver cirrhosis. Plasma IL
      1beta and IL-18 levels were examined by ELISA in patients with liver cirrhosis.
      RESULTS: Plasma IL-1beta and IL-18 levels were also significantly higher in
      patients with liver cirrhosis than in control subjects. Plasma IL-18 levels were
      significantly positively associated with Child-Pugh classification, IL-1beta
      levels, diastolic blood pressure, aspartate aminotransferase, total bilirubin,
      direct bilirubin, activated partial thromboplastin timealk and aline phosphatase.
      Plasma IL-18 levels were significantly negatively associated with albumin. NLRP3
      and cleaved caspase-1 expression were increased in the livers of patients with
      cirrhosis compared with the livers of control subjects. CONCLUSIONS: Plasma IL
      1beta and IL-18 levels were higher in plasma in patients with liver cirrhosis
      than in control subjects, and plasma IL-18 levels were significantly positively
      associated with Child-Pugh classification and IL-1beta levels. In addition, NLRP3
      and cleaved caspase-1 expression were increased in the livers of patients with
      cirrhosis.

PMID- 30236990
TI  - Evolutionary pathway for the 2017 emergence of a novel highly pathogenic avian
      influenza A(H7N9) virus among domestic poultry in Tennessee, United States.
AB  - In March 2017, a novel highly pathogenic avian influenza A(H7N9) virus was
      detected at two commercial broiler breeder facilities in Tennessee, United
      States. In this study, a wild bird low pathogenic avian influenza A virus, A/blue
      winged teal/Wyoming/AH0099021/2016(H7N9), was shown to be the probable precursor
      of the novel H7N9 virus; this low pathogenic virus has eight possible progenitor
      genes sharing > 99% sequence identity with the novel H7N9 virus. Phylogeographic
      analyses showed that viral gene constellations that formed and circulated among
      dabbling ducks contributed to the emergence of the novel H7N9 virus. This is in
      contrast to the virus that caused the 2016 H7N8 outbreak, which had more genetic
      contributions from viruses circulating among diving ducks. Study findings support
      the need for ongoing wild bird surveillance to monitor circulating viruses and to
      understand possible evolutionary pathways of virus emergence in poultry.

PMID- 30236991
TI  - Evaluation of the effects of chlorpyrifos combined with lipopolysaccharide stress
      on neuroinflammation and spatial memory in neonatal rats.
AB  - Chlorpyrifos (CPF) may weaken the immune defenses of children, making them
      vulnerable to opportunistic bacterial infection. CPF combined with bacterial
      infection is a potential problem for children during their childhood development.
      However, there is a lack of studies on the joint effects of these two factors on
      children. Here, we assessed the effects of CPF combined with lipopolysaccharide
      (LPS) on the inflammation and development of the nervous system. In this study,
      the cell toxicity of CPF plus LPS in cultured astrocytes, and the pathogenic
      effects of CPF plus LPS in neonatal rat models were observed. The hydrogen (H2)
      inhalation was used for treatment to explore its therapeutic potential. We found
      that CPF plus LPS activated the astrocyte, which increased the expressions of
      HMGB1, TLR4, and p-NF-kappaB p65, while H2-inhalation reduced the expressions (p
      < 0.05). We also found that CPF plus LPS induced long-lasting spatial memory
      deficits throughout brain maturation. However, H2-inhalation improved rat
      performance in these behavioral experiments (p < 0.05). In conclusion, the sub
      toxic concentration of CPF did not cause a significant damage in short term, but
      induced a severe long-term damage to the brain when combined with LPS. H2
      inhalation reduced the neuronal damage and behavioral abnormalities caused by CPF
      and LPS exposure.

PMID- 30236992
TI  - Human beta-defensin 1 update: Potential clinical applications of the restless
      warrior.
AB  - Human beta-defensin 1 (hBD-1) is a multifaceted antimicrobial peptide being a
      tumour suppressor and, depending on call of duty, capable of inducing self-nets
      and neutrophil extracellular traps (NETs) to capture and/or kill bacteria,
      participates in inflammatory responses in chronic diseases including hBD-3
      upregulation and also capable of up/downregulation in the presence of certain
      species of Lactobacillus sp. Thus, is regulated by host microbiota. Alleles,
      genotypes and/or altered gene expression of its coding gene, DEFB1, have been
      associated with several human diseases/conditions ranging from metabolic/chronic
      (e.g. cancer), infectious (e.g. tuberculosis, HIV/AIDS), inflammatory
      (gastrointestinal diseases), male infertility and more recently, neurologic (e.g.
      depression and Alzheimer) and autoimmune diseases (e.g. vitiligo and systemic
      lupus erythematosus). The present update focuses on novel DEFB1/hBD-1 properties
      and biomarker features, its biological function and the pharmaceutical potential
      uses of antimicrobial peptide elicitors (APEs) or the engineered peptide in the
      treatment of hBD-1-related human diseases.

PMID- 30236993
TI  - A MAPK/c-Jun-mediated switch regulates the initial adaptive and cell death
      responses to mitochondrial damage in a neuronal cell model.
AB  - Parkinson's disease (PD) is defined by the progressive loss of dopaminergic
      neurons. Mitochondrial dysfunction and oxidative stress are associated with PD
      although it is not fully understood how neurons respond to these stresses. How
      adaptive and apoptotic neuronal stress response pathways are regulated and the
      thresholds at which they are activated remains ambiguous. Utilising SH-SY5Y
      neuroblastoma cells, we show that MAPK/AP-1 pathways are critical in regulating
      the response to mitochondrial uncoupling. Here we found the AP-1 transcription
      factor c-Jun can act in either a pro- or anti-apoptotic manner, depending on the
      level of stress. JNK-mediated cell death in differentiated cells only occurred
      once a threshold of stress was surpassed. We also identified a novel feedback
      loop between Parkin activity and the c-Jun response, suggesting defective
      mitophagy may initiate MAPK/c-Jun-mediated neuronal loss observed in PD. Our data
      supports the hypothesis that blocking cell death pathways upstream of c-Jun as a
      therapeutic target in PD may not be appropriate due to crossover of the pro- and
      anti-apoptotic responses. Boosting adaptive responses or targeting specific
      aspects of the neuronal death response may therefore represent more viable
      therapeutic strategies.

PMID- 30236995
TI  - Another Vaccine. Another Meningococcal Vaccine. Another Adolescent Vaccine.
      Another Article About a Vaccine.

PMID- 30236994
TI  - Validation of a novel molecular RPA classification in glioblastoma (GBM-molRPA)
      treated with chemoradiation: A multi-institutional collaborative study.
AB  - BACKGROUND AND PURPOSE: A novel molecular recursive partitioning analysis
      classification has recently been reported integrating the MGMT promoter
      methylation (MGMTmeth) and IDH1 mutation (IDH1mut) status for glioblastoma (GBM
      molRPA) patients treated with temozolomide-based chemoradiation. The current
      study was initiated to validate the model in a multi-institutional study.
      MATERIALS AND METHODS: Four-hundred seventy-one newly diagnosed GBM patients
      (validation cohort) were allocated to classes I-III of the previously reported
      GBM-molRPA model. Of the patients, 15.7%, 56.1%, and 28.2% patients were GBM
      molRPA class I, II, and III, respectively. MGMTmeth and IDH1mut were observed in
      32.3 and 8.8% of patients, respectively. In the training plus validation cohort
      of 692 patients, 16.2%, 60.8%, and 23.0% patients were class I, II, and III,
      respectively. RESULTS: The median follow-up for survivors and the median survival
      (MS) of patients was 23.3 and 18.4 months, respectively. The MS for GBM-molRPA
      class I, II, and III was 49.7 (95% CI, 22.8-76.6), 19.2 (95% CI, 16.2-22.1), and
      13.8 months (95% CI, 11.8-15.4) (P < .001 for all comparisons) in the validation
      cohort. In the training plus validation cohort, the MS was 58.5 (95% CI, 40.7
      76.3), 21. (95% CI, 18.6-23.3), and 14.3 months (95% CI, 12.5-16.1) (P < .001 for
      all comparisons) for class I, II, and III, respectively. CONCLUSION: The GBM
      molRPA is a valid model. This GBM-molRPA classification can be useful in clinics
      and guiding patient stratification in future clinical trials.

PMID- 30236996
TI  - Meningococcal Group A, C, W, and Y Tetanus Toxoid Conjugate Vaccine: A Review of
      Clinical Data in Adolescents.
AB  - MenACWY-TT (Nimenrix) is a quadrivalent meningococcal vaccine containing
      polysaccharides from serogroups A, C, W, and Y conjugated to a tetanus toxoid
      carrier protein. MenACWY-TT is licensed in some countries as a three-dose primary
      series in individuals as young as 6 weeks of age and as a single dose in
      individuals >=12 months of age. MenACWY-TT use is supported by long-term
      immunogenicity and safety across age groups, including data from several phase 2,
      3, and 4 clinical studies in adolescents and young adults. Adolescents are an
      important population in the epidemiology, transmission, and prevention of
      invasive meningococcal disease, with this age-based population having the highest
      risk for carriage and transmission as well as one of the highest risks of
      disease. This age group is emerging as a target population in meningococcal
      vaccination programs globally, as vaccinating adolescents and young adults could
      potentially not only decrease disease rates directly for those vaccinated but
      also indirectly for unvaccinated individuals by decreasing carriage and eliciting
      herd protection. This review will consider available data for MenACWY-TT in
      adolescents, including safety and immunogenicity, booster and memory responses,
      persistence, and coadministration with other vaccines, with an emphasis on the
      rationale for use of MenACWY-TT and other quadrivalent meningococcal vaccines in
      adolescents to address the changing epidemiology of meningococcal disease.

PMID- 30236997
TI  - Evaluating Variability in Immunization Requirements and Policy Among U.S.
      Colleges and Universities.
AB  - OBJECTIVES: To evaluate variation in vaccine requirements, recommendations, and
      enforcement strategies among U.S. four-year colleges and universities. METHODS:
      We conducted a cross-sectional study abstracting information from Web sites among
      a sample of 216 four-year colleges and universities from all 50 states and
      District of Columbia. Our primary outcomes of interest included: type and number
      of vaccines required for school entry, vaccines recommended by schools for
      students, and vaccines supplied through student health services. Covariates of
      interest included: school type, region, school size, mention of American College
      Health Association recommendations, presence of an accredited health center,
      mention of state requirements, presence of an enforcement strategy, and exemption
      stringency of the state in which the school was located. RESULTS: Almost all
      (94%) schools required at least one vaccine for school entry, and 48% required
      three or more vaccines. The most commonly required vaccines were measles, mumps,
      and rubella (88.4%) and meningococcal vaccine (51.9%). All schools required the
      same vaccines included in state requirements but 65% also required additional
      vaccines. Most schools (67.1%) used registration hold to enforce requirements,
      while 14.8% restricted students from campus housing and 2.8% dismissed
      noncompliant students. Seventeen percent of schools had no published enforcement
      strategies. A higher proportion of private compared to public universities
      required three or more vaccines (57% vs. 37.3%, p = .014). CONCLUSIONS: While
      most schools have immunization requirements, there is significant variation in
      number and type of vaccines required. This suggests potential inconsistent uptake
      of recommended vaccines for college students and underlies the need to
      characterize facilitators and barriers to immunization program implementation on
      college campuses.

PMID- 30236998
TI  - Skills-Building Programs to Reduce Child Marriage in Bangladesh: A Randomized
      Controlled Trial.
AB  - PURPOSE: Child marriage is the norm in Bangladesh, leading to lifelong negative
      consequences. Evidence on sustainable child marriage programs is scant. Our study
      aimed to evaluate the impact of three community-based skills-building programs to
      delay child marriage among adolescent girls in rural Bangladesh. METHODS: The
      study used a cluster randomized controlled trial design with four arms-ARM1
      offered educational support, ARM2 promoted gender rights awareness, ARM3 offered
      livelihoods training, and ARM4 was a control area. All adolescent girls were
      offered 144 hours of skills training in village centers over 18 months. Among
      11,609 baseline survey respondents, 91% were successfully included in the endline
      analysis. Program impact was assessed using discrete time hazard models. RESULTS:
      The program reduced child marriages (<18) significantly in all arms relative to
      control-(adjusted hazard ratio [AHR]: .75; 95% confidence interval [CI]: .60-.92)
      for the education arm, (AHR: .72; 95% CI: .59-.88) for the gender arm, and (AHR:
      .70; 95% CI: .56-.87) for the livelihoods arm. Program participants were younger
      and more likely to be in school and faced lower risk of marriage relative to
      nonparticipants. In the gender and livelihoods arm, nonparticipants had lower
      risk of child marriage relative to the control group significant at the 10%
      level. CONCLUSIONS: The study demonstrates it is possible to reduce the
      prevalence of child marriage in a relatively short period of time by working with
      communities to implement holistic programs to build skills among girls. The
      program had similarly large impact and did not depend on the type of skills
      offered.

PMID- 30237000
TI  - Mental Health Disparities Among College Students of Color.
AB  - PURPOSE: Understanding the mental health needs of students of color is a growing
      priority on college and university campuses nationwide. This study aims to
      capture the state of mental health among students of color, including the
      prevalence of mental health problems and treatment utilization. METHODS: The
      sample is comprised of 43,375 undergraduate and graduate students at 60
      institutions that participated in the survey-based Healthy Minds Study from 2012
      to 2015. These data include over 13,000 students of color; we look separately at
      African-American, Latinx, Asian/Asian American, and Arab/Arab American students.
      Data are analyzed at the individual level using bivariate and multivariate
      modeling to elucidate variations across race/ethnicity. We examine symptom
      prevalence (measured by validated screens such as the Patient Health
      Questionnaire-9 for depression), help-seeking behaviors, and related factors
      (including knowledge and stigma). RESULTS: Across race/ethnicity, we find modest
      variation in symptom prevalence and larger variation in service utilization.
      Overall, treatment use is lower among students of color relative to white
      students, even when controlling for other variables in regression models.
      Asian/Asian American students have the lowest prevalence of treatment, at only
      20% among those with apparent mental health conditions. Attitudes related to
      mental health treatment also vary significantly and help to explain the primary
      findings. CONCLUSIONS: College students of color represent a disparities
      population based on greater levels of unmet mental health needs relative to white
      students. This paper takes an important step toward understanding these needs and
      points to implications for future research and practice.

PMID- 30236999
TI  - Differential Risk Factors for Unhealthy Weight Control Behaviors by Sex and
      Weight Status Among U.S. Adolescents.
AB  - PURPOSE: To determine if previously reported risk factors for the development of
      unhealthy weight control behaviors differ by sex and weight status using a
      nationally representative longitudinal sample of adolescents followed through
      young adulthood. METHODS: We used nationally representative longitudinal cohort
      data collected from baseline (11-18 years old, 1994-1995, Wave I) and seven-year
      follow-up (18-24 years old, 2001-2002, Wave III) of the National Longitudinal
      Study of Adolescent to Adult Health (Add Health). We examined potential risk
      factors (adverse childhood events and adolescent family, school, body image, and
      mental health factors) for the development of unhealthy weight control behaviors
      including vomiting, fasting/skipping meals, or laxative/diuretic use to lose
      weight at seven-year follow-up in young adulthood. RESULTS: Of the 14,322
      included subjects, 11% reported unhealthy weight control behavior at follow-up in
      young adulthood, with the highest proportion (23.7%) among overweight/obese
      females and the lowest proportion (3.7%) among underweight/normal weight males.
      All adolescent family factors were significantly associated with unhealthy weight
      control behaviors in underweight/normal weight females, whereas none were
      significantly associated in overweight/obese males. Similar trends were noted for
      adverse childhood events, and adolescent school and community factors. Adolescent
      self-perception of being overweight was associated with young adult unhealthy
      weight control behaviors among all subgroups. CONCLUSIONS: Risk factors for
      unhealthy weight control behaviors may differ based on sex and weight status.
      Screening, prevention, and treatment interventions for unhealthy weight control
      behaviors in adolescents and young adults may need to be tailored based on sex
      and weight status.

PMID- 30237001
TI  - Marijuana Legalization and Adolescent Health.

PMID- 30237002
TI  - Marijuana-Related Visits Were Too Broadly Defined to Draw Meaningful Conclusions.

PMID- 30237003
TI  - Marijuana Legalization and Adolescent Health.

PMID- 30237004
TI  - Global Adolescent Health Equity: A Brave New World.

PMID- 30237005
TI  - The Healthcare Needs and Rights of Youth Experiencing Homelessness.
AB  - The purpose of this position paper is to set forth guiding principles for working
      with youth experiencing homelessness (YEH). The Society for Adolescent Health and
      Medicine supports the following positions.

PMID- 30237006
TI  - Neutrophils contribute to vasculitis by increased release of neutrophil
      extracellular traps in Behcet's disease.
AB  - BACKGROUND AND OBJECTIVES: Behcet's disease (BD) is a multi-system inflammatory
      disorder that can cause vasculitis. Here we questioned whether Neutrophils in BD
      cause vasculitis via releasing Neutrophil Extracellular Traps (NETs), a process
      called NETosis. METHODS: Circulating neutrophils were isolated from a cohort of
      Middle Eastern BD patients with an active disease and healthy volunteers. The
      percentage of NETs release was monitored in neutrophils stimulated or not with BD
      serum, and treated or not with Colchicine, Dexamethasone, Cl-amidine or N-Acetyl
      Cysteine (NAC). The mRNA expression levels of PAD4 (a key enzyme in NETosis) was
      also assessed. The effect of NETs on the proliferation and cell death of
      endothelial cells was investigated using an in vitro co-culture model. The
      presence of NETs in skin tissues of BD patients was examined using immunolabeling
      of NETs associated proteins. RESULTS: Circulating Neutrophils from BD patients
      were more prone to release NETs in vitro and expressed higher levels of PAD4
      compared to healthy volunteers. Spontaneous NETs formation in BD neutrophils was
      inhibited by Colchicine and Dexamethasone, two drugs used to treat BD. NETs
      formation was also inhibited by Cl-amidine, a specific PAD4 inhibitor, and by
      NAC, a ROS inhibitor. Interestingly, serum from BD patients stimulated
      circulating neutrophils from healthy volunteers to release more NETs and
      increased their mRNA PAD4 expression. Moreover, endothelial cells cultured in the
      presence of NETs from BD patients showed a decrease in proliferation and an
      increase in apoptosis and cell death. Finally, NETosis was predominantly
      identified around affected blood vessels in biopsies of vasculitis from BD
      patients. CONCLUSION: Our results provide evidence on the implication of NETosis
      in the pathophysiology of BD especially in inducing vasculitis.

PMID- 30237007
TI  - Early postmortem interval estimation based on Cdc25b mRNA in rat cardiac tissue.
AB  - PURPOSE: The postmortem interval (PMI) is the amount of time that has elapsed
      since the time of death. Over the years, many approaches have been developed to
      assess PMI, but their time frame of applicability has been only days to weeks.
      Our present pilot study aimed to find the sensitive mRNA marker if the
      degradation of mRNA could be used to estimate the early postmortem interval (up
      to 24 h). METHODS: In our study, we use the microarray to screen 217 mRNAs
      markers of rat cardiac tissue. Then, real-time fluorescent quantitative PCR
      (qPCR) was used to validate of the candidate markers at 7 time points within 24 h
      and at temperatures of 25  degrees C and 35  degrees C. Another 27 rats were then
      used to verify the model. RESULTS: Among all of the candidate markers, ?Cq (cell
      division cycle 25 homolog B(Cdc25b)) had the best correlation coefficient with
      early postmortem interval and was used to build a new model using the R software.
      The results of verification testing demonstrated that the error rate was less
      than 15%, demonstrating the high predictive power of our mathematical model.
      CONCLUSION: In this study, Cdc25b was found to be the sensitive marker to
      estimate early postmortem interval, and Rpl27 was found to be suitable for use as
      the endogenous control. Our work provided new leads for molecular approaches to
      early postmortem interval estimation using the significant mRNA markers
      established here.

PMID- 30237008
TI  - Synthesis of mycosporine-like amino acids by a size-fractionated marine
      phytoplankton community of the arctic beaufort sea.
AB  - During the RV-ARAON cruise, a comparative study on the biosynthesis of
      mycosporine-like amino acids (MAAs) was conducted for the size-fractionated
      phytoplankton of the Beaufort Sea (Arctic). The MAAs contents in the micro
      phytoplankton community (>20 MUm size) is considerably higher than that observed
      in the nano- (20-2 MUm size) and pico-phytoplankton (<2 MUm size) communities.
      The micro-phytoplankton of the Mackenzie Shelf had a relatively higher
      Chlorophyll a (Chl a) concentration. Considering the total phytoplankton
      community, the MAAs concentration as well as net production of individual MAAs
      (such as shinorine and palythine) were higher at the Mackenzie Shelf rather than
      at the sites located beyond the Beaufort Sea; precisely, the highest net
      production rates of shinorine and palythine were 0.211 (+/-0.02) ng C L-1 d-1 and
      0.136 (+/-0.001) ng C L-1 d-1 respectively (No other MAAs were detected). The
      micro-phytoplankton used around 0.5% of the total carbon uptake for the synthesis
      of MAAs. Compared to the smaller phytoplankton community, the micro-phytoplankton
      utilized more of their energy for the biosynthesis of MAAs; on the other hand,
      nano- and pico-phytoplankton focused on cellular activity and had poor
      biosynthesis of MAAs. This clearly indicates the phytoplankton size-dependent
      variation in the biosynthesis of MAA in the natural phytoplankton community. This
      study revealed the environmental adaptation of the various sizes of phytoplankton
      community as well as their physiological response in the Arctic Beaufort Sea.

PMID- 30237009
TI  - Do community pharmacist performance evaluations capture the modern pharmacist's
      role? Mapping competencies assessed in Canadian community pharmacy performance
      evaluation templates against the General Level Framework.
AB  - OBJECTIVES: Feedback on community pharmacists' practice is limited after
      graduation and often comes in the form of annual performance evaluations by
      pharmacy managers based on company-provided templates. The objective of this
      study was to examine the relevance of these review processes to all aspects of
      community pharmacy practice. METHODS: Competencies evaluated in performance
      evaluation templates used by pharmacy organizations were mapped to the General
      Level Framework (GLF)-a tool developed to assess the competency of general-level
      pharmacy practitioners-and studied in hospital and community practice settings.
      The competencies were further assessed with consideration of their applicability
      to the current scope of practice of Canadian community pharmacy practice.
      RESULTS: Performance evaluation templates from 7 community pharmacy organizations
      in Canada were obtained and evaluated. Performance evaluations mapped most
      closely to the GLF tool related to personal competencies (e.g., organization,
      communication, and teamwork), with the lowest level of congruence observed among
      competencies specific to patient care activities. Few evaluations considered
      recent expansions of scope in place across various Canadian provinces, such as
      ordering and interpreting laboratory tests or pharmacist prescribing. CONCLUSION:
      Performance evaluation can be a valuable tool to improve quality of care and the
      professional development of pharmacists; however, these tools should be
      reexamined to ensure that feedback on the most valuable aspects of a pharmacist's
      professional practice is the focus. As pharmacy practice continues to evolve
      toward greater direct patient care activities, so too should our evaluation tools
      align with this increasingly recognized role.

PMID- 30237010
TI  - Add-on rTMS for the acute treatment of depressive symptoms is probably more
      effective in adolescents than in adults: Evidence from real-world clinical
      practice.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is considered as
      an effective treatment for adults with major depressive disorder. However, it
      remains unknown whether rTMS has comparable or better efficacy in adolescents.
      OBJECTIVE: The current naturalistic study aimed to investigate the efficacy and
      clinical outcome of add-on rTMS in a large sample of adolescent patients compared
      to adult patients. METHODS: This study included 117 patients (42 adolescents vs.
      75 adults) with mood or anxiety disorders who were treated with at least 10
      sessions of rTMS. rTMS was applied over the left dorsolateral prefrontal cortex
      (10 Hz). Symptoms of depression and anxiety were measured using the Hamilton
      Rating Scale for Depression (HAMD) and the Hamilton Rating Scale for Anxiety
      (HAMA) respectively, at baseline and after 2 and 4 weeks of follow-up.
      Comparisons of clinical improvement and rates of response/remission were made
      across age groups. MAJOR FINDINGS AND CONCLUSIONS: All the age groups showed
      significant improvements in clinical symptoms. No safety or tolerability concerns
      were identified. Symptomatic improvements and response/remission rates were more
      significant in adolescent patients than in adults. Decrease in HAMD and HAMA
      scores after 2 weeks and 4 weeks of rTMS treatment were positively correlated in
      adolescents, but not in adults. General linear model repeated measures
      demonstrated significant effect of time * age group interaction on the HAMD
      score, in response to 10 sessions of rTMS. Add-on rTMS is feasible, tolerable,
      effective and more applicable to adolescents with mood or anxiety disorders.
      However, double-blinded and sham-controlled trials are needed for validating this
      conclusion.

PMID- 30237011
TI  - Significance of neck dissection for the treatment of clinically-evident medullary
      thyroid carcinomas: A systematic review.
AB  - OBJECTIVE: The survival benefit of prophylactic lateral neck dissection in
      medullary thyroid carcinomas remains unclear; thus, recent clinical guidelines
      have deferred the recommendation of lateral neck dissection. This review is to
      assess the role of lateral neck dissection in treatment of clinically overt
      medullary thyroid carcinoma. METHODS: A meta-analysis was performed on full-text
      publications written in English sourced using Embase and Medline databases.
      Publications with data regarding lateral neck dissection and clinical outcome
      were included. RESULTS: The frequently performed central neck dissection was
      significantly correlated with a higher biological cure rate (p=0.047) and lower
      structural recurrence rate (p=0.002). The frequency of ipsilateral lateral neck
      dissection was significantly negatively correlated with the rate of died of
      disease (p=0.017). CONCLUSION: The frequency of lateral neck dissections and rate
      of died of disease had a reverse correlation suggesting that prophylactic lateral
      neck dissection has a significant impact on survival.

PMID- 30237012
TI  - Long-term mortality and estimated functional capacity among women with symptoms
      of ischemic heart disease: From the NHLBI-sponsored Women's Ischemia Syndrome
      Evaluation.
AB  - The aim of this study was to determine the long-term prognostic value of the Duke
      Activity Status Index-estimated metabolic equivalents (METs) values among women
      with suspected ischemic heart disease. At a median of 9.6 years, the incidence of
      death was 23.4% in those with METs <4.8 versus 8.2% in METs >9.9, P < .01. In
      conclusion, use of the simple, patient-reported Duke Activity Status Index could
      help identify higher-risk women with suspected ischemic heart disease for
      targeted risk management.

PMID- 30237013
TI  - Glucose production from cellulose through biological simultaneous enzyme
      production and saccharification using recombinant bacteria expressing the beta
      glucosidase gene.
AB  - Efficient cellulosic biomass saccharification technologies are required to meet
      biorefinery standards. Biological simultaneous enzyme production and
      saccharification (BSES), which is glucose production from cellulosic biomass by
      Clostridium thermocellum, can be a reliable cellulose saccharification technology
      for biorefineries. However, the current BSES processes require purified beta
      glucosidase supplementation. In this study, recombinant bacteria expressing the
      beta-glucosidase gene were developed and directly applied to BSES. The engineered
      Escherichia coli expressing the thermostable beta-glucosidase gene from
      Thermoanaerobacter brockii exhibited 0.5 U/ml of beta-glucosidase activities. The
      signal peptide sequence of lytF gene from Bacillus subtilis was the most
      appropriate for the beta-glucosidase secretion from Brevibacillus choshinensis,
      and the broth exhibited 0.74 U/ml of beta-glucosidase activities. The engineered
      E. coli and B. choshinensis expressing the thermostable beta-glucosidase gene
      produced 47.4 g/L glucose and 49.4 g/L glucose, respectively. Glucose was
      produced by the hydrolysis of 100 g/L Avicel cellulose for 10 days through BSES,
      and the product yield was similar to that obtained through BSES with purified
      beta-glucosidase supplementation. Our findings indicate that the direct
      supplementation of beta-glucosidase using bacterial cells expressing beta
      glucosidase gene or their broth was applicable to BSES, suggesting the potential
      of this process as a cost-effective approach to cellulose saccharification.

PMID- 30237014
TI  - Predicting the risk of acute care readmissions among rehabilitation inpatients: A
      machine learning approach.
AB  - INTRODUCTION: Readmission from inpatient rehabilitation facilities to acute care
      hospitals is a serious problem. This study aims to develop a predictive model
      based on machine learning algorithms to identify patients at high risk of
      readmission. METHODS: A retrospective dataset (2001-2017) including 16,902
      patients admitted into a large inpatient rehabilitation facility in North
      Carolina was collected in 2017. Three types of machine learning models with
      different predictors were compared in 2018. The model with the highest c
      statistic was selected as the best model and further tested by using five sets of
      training and validation data with different split time. The optimum threshold for
      classification was identified. RESULTS: The logistic regression model with only
      functional independence measures has the highest validation c-statistic at 0.852.
      Using this model to predict the recent 5 years acute care readmissions yielded
      high discriminative ability (c-statistics: 0.841-0.869). Larger training data
      yielded better performance on the test data. The default cutoff (0.5) resulted in
      high specificity (>0.997) but low sensitivity (<0.07). The optimum threshold
      helped to achieve a balance between sensitivity (0.754-0.867) and specificity
      (0.747-0.780). CONCLUSIONS: This study demonstrates that functional independence
      measures can be analyzed by using machine learning algorithms to predict acute
      care readmissions, thus improving the effectiveness of preventive medicine.

PMID- 30237015
TI  - Correction to Lancet Glob Health 2018; 6: e1100-21.

PMID- 30237016
TI  - Review on the relevance of therapeutic drug monitoring of levetiracetam.
AB  - Therapeutic Drug Monitoring (TDM) of anti-epileptic drugs (AEDs) is not routinely
      performed, although this can guide the dosage regimen to achieve greater efficacy
      and safety. Levetiracetam (LEV) has been introduced as an AED with an almost
      perfect pharmacokinetic (PK) profile. Nonetheless, recent research challenges
      this statement and therefore we aimed to explore factors that modify LEV PK. Age
      and enzyme-inducing drugs (EIDs) appear to be major factors influencing the PK
      profile of LEV. Therefore, 30-50% lower dosages should be used in the elderly (>
      65 years of age) and the dosing regimen should be guided by monitoring SDC (TDM).
      In contrast, higher LEV dosages are necessary in children aged between 2 months
      and 12 years (compared to adults) due to a 30-70% increase of LEV clearance (CL).
      Higher dosages are also required if a patient receives EIDs, again due to a
      higher CL of LEV (range 24-60%). This could also be true for pregnant women. LEV
      TDM is currently not common in the clinical setting due to the wide therapeutic
      range and the low prevalence of side-effects. However, LEV dose should on the one
      hand be increased in certain physiological situations (pregnancy, neonates) and
      patients on EIDs (especially carbamazepine). On the other hand, dose reductions
      are necessary when the LEV CL is impaired (elderly). Nevertheless, current data
      to support regular LEV TDM are lacking. Prospective research is needed to explore
      the importance of LEV TDM in elected patient groups; i.e. neonates, elderly,
      patients on EIDs and pregnant women.

PMID- 30237017
TI  - [Should we "dumb it down"... or "train it up"?... Breaking barriers and changing
      the culture of resuscitation].

PMID- 30237018
TI  - [Volunteering and cooperation among medical students. An observational
      questionnaire study].

PMID- 30237019
TI  - [Multiple birth trends in the region of Castilla y Leon (Spain) in a 13 year
      period].
AB  - INTRODUCTION: Multiple pregnancy has increased in prevalence in the last few
      years, which could lead to more foetal and maternal morbidity issues. The aim of
      this study is to describe the trend of multiple pregnancy deliveries in Castilla
      y Leon during the last 13years and the subsequent impact on foetal and maternal
      health. MATERIAL AND METHODS: Data was collected from the hospital discharge
      reports registered in the Regional Health-care database (SACYL: Health care in
      Castilla y Leon) between 2001 and 2013. A cross sectional descriptive study was
      conducted, including trend analysis with log-linear joint point model, a rhythm
      metric study, as well as a risk assessment with multivariate analysis. RESULTS: A
      pronounced upward trend was observed in the proportion of multiple deliveries in
      this time period, compared to single ones, with an annual percentage change of
      3.4% (95% CI: 2.5-4.4). Multiple pregnancy was significantly correlated with
      advanced maternal age, abnormal glucose tolerance, dystocia and caesarean section
      delivery, premature birth, foetal malposition, foetal macrosomia, stillbirth, in
      vitro fertilisation, and hypertensive episodes of pregnancy. In vitro
      fertilization showed a 9.3 fold increased risk in multiple pregnancy (95% CI: 7.4
      11.5), with maternal age increasing the risk up to 5% per year of age (OR: 1.05:
      95%CI: 1.04-1.05). No seasonal rhythm was observed in multiple deliveries
      compared with single ones. CONCLUSION: Multiple pregnancy has experienced a
      continuous increase, with no seasonal trend, and is associated with the increase
      in assisted reproductive technology and advanced maternal age. This involves more
      problems regarding foetal and maternal morbidity and mortality.

PMID- 30237020
TI  - Clinical Efficacy of Injection and Mechanical Therapy for Peyronie's Disease: A
      Systematic Review of the Literature.
AB  - CONTEXT: Conservative therapies for Peyronie's disease (PD) aim to treat early
      stage disease by improving clinical outcomes such as penile curvature, penile
      length erectile dysfunction, and pain. OBJECTIVE: To summarise the available
      evidence regarding injection and mechanical therapies for PD treatment. EVIDENCE
      ACQUISITION: An extensive search of Medline, Embase, and Scopus databases
      retrieved English-language articles up to 15 May 2018. The systematic review
      protocol was registered on PROSPERO (CRD42017077050). Inclusion criteria were as
      follows: adults with early or chronic PD receiving treatment with injection
      therapy, penile traction, or a vacuum device. EVIDENCE SYNTHESIS: Fifty-two
      articles were selected according to the inclusion criteria-17 comparative studies
      and 35 cohort studies-analysing the effects of calcium channel blockers
      (verapamil, nicardipine), collagenase Clostridium histolyticum (CCH), interferon
      alpha-2b (IFNalpha-2b), hyaluronic acid (HA), onabotulinum toxin A,
      thiocolchicine, penile extender devices, and vacuum devices. Qualitative data
      from these studies suggest a clinically significant effect of CCH and IFNalpha-2b
      injection therapy to decrease penile curvature and conserve penile length.
      Verapamil and HA performed well in single-arm or case-control studies. Studies of
      penile traction and vacuum devices in patients with PD demonstrated some benefits
      in terms of curvature and penile length but only in small, underpowered,
      nonrandomised studies. Studies of onabotulinum toxin A injections or
      thiocolchicine showed significant improvements in penile curvature, but only in
      studies of single-arm or case-control design. CONCLUSIONS: CCH and IFNalpha-2b
      injected into stable PD plaques can decrease penile curvature; CCH can also
      improve penile length. However, based on available data, strong conclusions
      cannot be drawn for other treatments, including calcium channel blockers, HA, or
      mechanical therapies. PATIENT SUMMARY: Our systematic review of injection
      therapies provides evidence for improvements in penile curvature for patients
      with Peyronie's disease. No robust evidence is available to support the use of
      other local treatments including calcium channel blockers, hyaluronic acid, or
      mechanical therapies.

PMID- 30237022
TI  - Molecular Subtypes of Bladder Cancer: Academic Exercise or Clinical Relevance?

PMID- 30237021
TI  - Are We Improving Erectile Function Recovery After Radical Prostatectomy? Analysis
      of Patients Treated over the Last Decade.
AB  - BACKGROUND: The last decade has seen several advances in radical prostatectomy
      (RP) technique and post-RP care that are relevant to erectile function (EF)
      recovery. OBJECTIVE: We examined whether these practice changes have led to
      observed improvements in EF rates over time. DESIGN, SETTING, AND PARTICIPANTS:
      We identified 2364 patients treated with either open or minimally-invasive RP at
      a single academic center in 2008-2015. To mitigate confounding by the surgical
      learning curve, only patients treated by surgeons who performed at least 100
      procedures were considered. INTERVENTION: EF before and after RP was assessed by
      the International Index of Erectile Function 6 (IIEF-6), with recovery defined as
      IIEF-6 >=24. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analyzed EF
      recovery rates of patients treated with bilateral nerve-sparing surgery and free
      from adjuvant/salvage treatment at the time of EF assessment. Local polynomial
      regression analyses explored changes in the outcomes over time. Linear and
      logistic regression analyses were used to estimate the influence of year of
      surgery on baseline variables and EF recovery. RESULTS AND LIMITATIONS: We
      observed a significant decrease over time of the EF recovery rates at both 12 and
      24mo post-RP (all p=0.01). However, patient's age at surgery increased over time
      (mean increase of 0.5 per year; p<0.01), with a resultant increase in risk of
      comorbidity (odds ratio [OR]=1.1, 95% confidence interval [CI]: 1.02-1.15;
      p=0.008) and thus decrease in baseline IIEF-6 score (0.35 points per year;
      p=0.0003). After accounting for baseline and pathological characteristics,
      urinary function, and type of surgery in a multivariable analysis, year of
      surgery was not associated with EF recovery (12mo: OR=0.97, 95% CI: 0.91-1.03,
      p=0.4; 24mo: OR=0.97, 95% CI: 0.91-1.03, p=0.3). CONCLUSIONS: Findings from a
      high-volume center suggest that, despite the advancements in surgical and
      postoperative care, EF outcomes after RP have not improved over the last decade.
      Additional strategies are required to improve EF recovery after RP. PATIENT
      SUMMARY: The probability of regaining potency after surgery for prostate cancer
      did not improve over the last decade; more efforts are needed to improve
      patient's care after radical prostatectomy.

PMID- 30237023
TI  - A Prospective Adaptive Utility Trial to Validate Performance of a Novel Urine
      Exosome Gene Expression Assay to Predict High-grade Prostate Cancer in Patients
      with Prostate-specific Antigen 2-10ng/ml at Initial Biopsy.
AB  - BACKGROUND: Discriminating indolent from clinically significant prostate cancer
      (PCa) in the initial biopsy setting remains an important issue. Prospectively
      evaluated diagnostic assays are necessary to ensure efficacy and clinical
      adoption. OBJECTIVE: Performance and utility assessment of ExoDx Prostate
      (IntelliScore) (EPI) urine exosome gene expression assay versus standard clinical
      parameters for discriminating Grade Group (GG) >=2 PCa from GG1 PCa and benign
      disease on initial biopsy. DESIGN, SETTING, AND PARTICIPANTS: A two-phase
      adaptive clinical utility study (NCT03031418) comparing EPI results with biopsy
      outcomes in men, with age >=50 yr and prostate-specific antigen (PSA) 2-10ng/ml,
      scheduled for initial prostate biopsy. After EPI performance assessment during
      phase I, a clinical implementation document (ie, CarePath) was developed for
      utilizing the EPI test in phase II, where the biopsy decision is uncertain.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance evaluation of the EPI
      test in patients enrolled in phase I and publication of a consensus CarePath for
      phase II. RESULTS AND LIMITATIONS: In a total of 503 patients, with median age of
      64 yr, median PSA 5.4ng/ml, 14% African American, 70% Caucasian, 53% positive
      biopsy rate (22% GG1, 17% GG2, and 15% >= GG3), EPI was superior to an optimized
      model of standard clinical parameters with an area under the curve (AUC) 0.70
      versus 0.62, respectively, comparable with previously published results (n=519
      patients, EPI AUC 0.71). Validated cut-point 15.6 would avoid 26% of unnecessary
      prostate biopsies and 20% of total biopsies, with negative predictive value (NPV)
      89% and missing 7% of >=GG2 PCa. Alternative cut-point 20 would avoid 40% of
      unnecessary biopsies and 31% of total biopsies, with NPV 89% and missing 11% of
      >=GG2 PCa. The clinical investigators reached consensus recommending use of the
      15.6 cut-point for phase II. Outcome of the decision impact cohort in phase II
      will be reported separately. CONCLUSIONS: EPI is a noninvasive, easy-to-use, gene
      expression urine assay, which has now been successfully validated in over 1000
      patients across two prospective validation trials to stratify risk of >=GG2 from
      GG1 cancer and benign disease. The test improves identification of patients with
      higher grade disease and would reduce the total number of unnecessary biopsies.
      PATIENT SUMMARY: It is challenging to predict which men are likely to have high
      grade prostate cancer (PCa) at initial biopsy with prostate-specific antigen 2
      10ng/ml. This study further demonstrates that the ExoDx Prostate (IntelliScore)
      test can predict >=GG2 PCa at initial biopsy and defer unnecessary biopsies
      better than existing risk calculator's and standard clinical data.

PMID- 30237024
TI  - Reply to Massimo Valerio, Mark Emberton, and Hashim U. Ahmed's Letter to the
      Editor re: Henk G. van der Poel, Roderick C.N. van den Bergh, Erik Briers, et al.
      Focal Therapy in Primary Localised Prostate Cancer: The European Association of
      Urology Position in 2018. Eur Urol 2018;74:84-91.

PMID- 30237025
TI  - Re: Tom J.H. Arends, Ofer Nativ, Massimo Maffezzini, et al. Results of a
      Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with
      Mitomycin C Versus Bacillus Calmette-Guerin for Adjuvant Treatment of Patients
      with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer. Eur Urol
      2016;69:1046-52.

PMID- 30237026
TI  - Do We Truly Care About the Functional Outcomes for Renal Cancer Patients?
      Multidisciplinarity Is Still Far Away.

PMID- 30237027
TI  - Baseline Prostate-specific Antigen Level in Midlife and Aggressive Prostate
      Cancer in Black Men.
AB  - BACKGROUND: Prostate-specific antigen (PSA) measurement in midlife predicts long
      term prostate cancer (PCa) mortality among white men. OBJECTIVE: To determine
      whether baseline PSA level during midlife predicts risk of aggressive PCa in
      black men. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study among
      black men in the Southern Community Cohort Study recruited between 2002 and 2009.
      A prospective cohort in the southeastern USA with recruitment from community
      health centers. A total of 197 incident PCa patients aged 40-64 yr at study entry
      and 569 controls matched on age, date of blood draw, and site of enrollment.
      Total PSA was measured in blood collected and stored at enrollment. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Total and aggressive PCa (91 aggressive:
      Gleason >=7, American Joint Committee on Cancer stage III/IV, or PCa-specific
      death). Exact conditional logistic regression estimated odds ratios (ORs) with
      95% confidence intervals (CIs) for PCa by category of baseline PSA. RESULTS AND
      LIMITATIONS: Median PSA among controls was 0.72, 0.80, 0.94, and 1.03ng/ml for
      age groups 40-49, 50-54, 55-59, and 60-64 yr, respectively; 90th percentile
      levels were 1.68, 1.85, 2.73, and 3.33ng/ml. Furthermore, 95% of total and 97% of
      aggressive cases had baseline PSA above the age-specific median. Median follow-up
      was 9 yr. The OR for total PCa comparing PSA >90th percentile versus <=median was
      83.6 (95% CI, 21.2-539) for 40-54 yr and 71.7 (95% CI, 23.3-288) for 55-64 yr.
      For aggressive cancer, ORs were 174 (95% CI, 32.3-infinity) for 40-54 yr and 51.8
      (95% CI, 11.0-519) for 55-64 yr. A composite endpoint of aggressive PCa based on
      stage, grade, and mortality was used and is a limitation. CONCLUSIONS: PSA levels
      in midlife strongly predicted total and aggressive PCa among black men. PSA
      levels among controls were similar to those among white controls in prior
      studies. PATIENT SUMMARY: Prostate-specific antigen (PSA) level during midlife
      strongly predicted future development of aggressive prostate cancer among black
      men. Targeted screening based on a midlife PSA might identify men at high risk
      while minimizing screening in those men at low risk.

PMID- 30237028
TI  - Greater susceptibility of girls to airborne Benzo[a]pyrene for obesity-associated
      childhood asthma.
AB  - BACKGROUND: Sexually dimorphic risk of obesity-associated asthma is posited to
      accelerate around puberty. Yet, the role of air pollution on the lean and obese
      asthmatic children has never been examined. OBJECTIVE: To compare whether a unit
      exposure to airborne benzo[a]pyrene (B[a]P) is associated with altered risks of
      asthma across the overweight/obese (OV/OB) control, lean asthmatic, and OV/OB
      asthmatic children, respectively, compared to the lean controls, before and after
      adjusting for oxidant stress markers (i.e. 15-F2t-IsoP, 8-oxo-dG, and Carbonyl).
      METHODS: Asthmatic and healthy control children, recruited from polluted urban
      and rural areas, were matched to ambient concentration of B[a]P. A unit increase
      in B[a]P and multinomial logistic regression on OV/OB control, lean asthmatic,
      and OV/OB asthma were compared across the sex- and age-groups. RESULTS: The
      median B[a]P was associated with a linear increase among the female children,
      according to OV/OB and asthma, respectively, and together, compared to the lean
      control girls (p = 0.001). While B[a]P was associated with positive relationship
      with 15-F2t-IsoP level among the OV/OB boys, the same exposure-outcome
      association was inverse among the OV/OB girls. One natural log-unit increase in
      ambient B[a]P was associated with 10.5-times greater odds (95% CI, 2.6-39.6; p =
      0.001) the adolescent OV/OB boys, compared to the unit odds among the lean
      controls. In contrast, the adolescent OV/OB girls were associated with highest
      adjusted odds of the asthma (aOR = 15.4; 95% CI, 2.9-29.1; p < 0.001) compared to
      the lean control girls. An adjustment for 15-F2t-IsoP, and Carbonyls was
      associated with greater odds of asthma per unit exposure for the adolescent OV/OB
      girls (aOR = 16.2; 95% CI, 1.4-181.8; p = 0.024). CONCLUSIONS: B[a]P exposure was
      associated with a leap in the odds of asthma among the OV/OB adolescents,
      particularly the girls, after adjusting for 15-F2t-IsoP and Carbonyls.

PMID- 30237029
TI  - Quantitative Laser Diffraction for Quantification of Protein Aggregates:
      Comparison With Resonant Mass Measurement, Nanoparticle Tracking Analysis, Flow
      Imaging, and Light Obscuration.
AB  - In the past, analysis of micron-sized (>1.0 MUm) aggregates of therapeutic
      proteins has been limited to light obscuration (LO), and appropriate quantitative
      methods of evaluating protein aggregates need to be developed. Recently, novel
      methods with enhanced reliability and sensitivity, such as nanoparticle tracking
      analysis (NTA), resonant mass measurement (RMM), and flow imaging (FI), have
      emerged. We have found that quantitative laser diffraction (qLD) is also
      effective for quantitative evaluation of protein aggregates over a wide size
      range. However, the different detection principles of the methods potentially
      lead to inconsistencies in results. This study aimed to compare particle size
      distributions and concentrations of protein aggregates using the orthogonal
      methods. Protein aggregates were generated by stirring an immunoglobulin
      solution. Serial dilutions of the aggregates stock were analyzed by RMM, FI, and
      qLD to obtain the particle size distribution and concentration using each method.
      In addition, size distribution of a protein aggregates solution was compared by
      RMM, NTA, FI, LO, and qLD. Both particle size distribution and concentration were
      in good agreement between RMM and qLD (0.3-2 MUm) and between FI and qLD (2-20
      MUm). Thus, we concluded that qLD enables covering of the overlapping particle
      size range between RMM and FI.

PMID- 30237030
TI  - The Effects of Feed Frame Parameters and Turret Speed on Mini-Tablet Compression.
AB  - Die filling is a critical process step during tablet production as it defines the
      tablet weight. Achieving die fill consistency during production of mini-tablets,
      tablets with diameters <=6 mm, is considerably more challenging. Although die
      filling in rotary presses had been studied in relation to the feed paddle design,
      paddle speed, and turret speed, it is unclear how these process variables could
      impact mini-tablet production and product properties. In this study, 1.8 and 3 mm
      mini-tablets were prepared using a rotary press with multiple-tip tooling using
      different process configurations. Mini-tablet weight variation within and across
      compaction cycles were determined using data from compression roller displacement
      and mini-tablet weight. Higher die fill densities were achieved with a flat feed
      wheel paddle and high paddle speed. This was attributed to better granule
      fluidization in the feed frame, which also increased the intercycle weight
      variation and reduced tensile strength. The turret speed did not impact mini
      tablet properties significantly. Granule overlubrication in the feed frame
      potentially reduced mini-tablet tensile strength during compaction. The number of
      paddle passes in the die fill region was correlated to mini-tablet die fill
      performance. Findings from this study could provide better insights into the
      relationship between process variables and mini-tablet product quality.

PMID- 30237031
TI  - Characteristics of ambient bioaerosols during haze episodes in China: A review.
AB  - Frequent low visibility, haze pollution caused by heavy fine particulate matter
      (PM2.5) loading, has been entailing significant environmental issues and health
      risks in China since 2013. A substantial fraction of bioaerosols was observed in
      PM (1.5-15%) during haze periods with intensive pollution. However, systematic
      and consistent results of the variations of bioaerosol characteristics during
      haze pollution are lacking. The role of bioaerosols in air quality and
      interaction with environment conditions are not yet well characterized. The
      present article provides an overview of the state of bioaerosol research during
      haze episodes based on numerous recent studies over the past decade, focusing on
      concentration, size distribution, community structure, and influence factors.
      Examples of insightful results highlighted the characteristics of bioaerosols at
      different air pollution levels and their pollution effects. We summarize the
      influences of meteorological and environmental factors on the distribution of
      bioaerosols. Further studies on bioaerosols, applying standardized sampling and
      identification criteria and investigating the influence of mechanisms of
      environmental or pollution factors on bioaerosols as well as the sources of
      bioaerosols are proposed.

PMID- 30237032
TI  - The alteration landscape of the cerebral cortex.
AB  - Growing evidence is challenging the assumption that brain disorders are
      diagnostically clear-cut categories. Transdiagnostic studies show that a set of
      cerebral areas is frequently altered in a variety of psychiatric as well as
      neurological syndromes. In order to provide a map of the altered areas in the
      pathological brain we devised a metric, called alteration entropy (A-entropy),
      capable of denoting the "structural alteration variety" of an altered region.
      Using the whole voxel-based morphometry database of BrainMap, we were able to
      differentiate the brain areas exhibiting a high degree of overlap between
      different neuropathologies (or high value of A-entropy) from those exhibiting a
      low degree of overlap (or low value of A-entropy). The former, which are parts of
      large-scale brain networks with attentional, emotional, salience, and premotor
      functions, are thought to be more vulnerable to a great range of brain diseases;
      while the latter, which include the sensorimotor, visual, inferior temporal, and
      supramarginal regions, are thought to be more informative about the specific
      impact of brain diseases. Since low A-entropy areas appear to be altered by a
      smaller number of brain disorders, they are more informative than the areas
      characterized by high values of A-entropy. It is also noteworthy that even the
      areas showing low values of A-entropy are substantially altered by a variety of
      brain disorders. In fact, no cerebral area appears to be only altered by a
      specific disorder. Our study shows that the overlap of areas with high A-entropy
      provides support for a transdiagnostic approach to brain disorders but, at the
      same time, suggests that fruitful differences can be traced among brain diseases,
      as some areas can exhibit an alteration profile more specific to certain
      disorders than to others.

PMID- 30237034
TI  - Background connectivity between frontal and sensory cortex depends on task state,
      independent of stimulus modality.
AB  - The human brain has the ability to process identical information differently
      depending on the task. In order to perform a given task, the brain must select
      and react to the appropriate stimuli while ignoring other irrelevant stimuli. The
      dynamic nature of environmental stimuli and behavioral intentions requires an
      equally dynamic set of responses within the brain. Collectively, these responses
      act to set up and maintain states needed to perform a given task. However, the
      mechanisms that allow for setting up and maintaining a task state are not fully
      understood. Prior evidence suggests that one possible mechanism for maintaining a
      task state may be through altering 'background connectivity,' connectivity that
      exists independently of the trials of a task. Although previous studies have
      suggested that background connectivity contributes to a task state, these studies
      have typically not controlled for stimulus characteristics, or have focused
      primarily on relationships among areas involved with visual sensory processing.
      In the present study we examined background connectivity during tasks involving
      both visual and auditory stimuli. We examined the connectivity profiles of both
      visual and auditory sensory cortex that allow for selection of task-relevant
      stimuli, demonstrating the existence of a potentially universal pattern of
      background connectivity underlying attention to a stimulus. Participants were
      presented with simultaneous auditory and visual stimuli and were instructed to
      respond to only one, while ignoring the other. Using functional MRI, we observed
      task-based modulation of the background connectivity profile for both the
      auditory and visual cortex to certain brain regions. There was an increase in
      background connectivity between the task-relevant sensory cortex and control
      areas in the frontal cortex. This increase in synchrony when receiving the task
      relevant stimulus as compared to the task irrelevant stimulus may be maintaining
      paths for passing information within the cortex. These task-based modulations of
      connectivity occur independently of stimuli and could be one way the brain sets
      up and maintains a task state.

PMID- 30237033
TI  - Human Connectome Project-style resting-state functional MRI at 7 Tesla using
      radiofrequency parallel transmission.
AB  - We investigate the utility of radiofrequency (RF) parallel transmission (pTx) for
      whole-brain resting-state functional MRI (rfMRI) acquisition at 7 Tesla (7T). To
      this end, Human Connectome Project (HCP)-style data acquisitions were chosen as a
      showcase example. Five healthy subjects were scanned in pTx and single-channel
      transmit (1Tx) modes. The pTx data were acquired using a prototype 16-channel
      transmit system and a commercially available Nova 8-channel transmit 32-channel
      receive RF head coil. Additionally, pTx single-spoke multiband (MB) pulses were
      designed to image sagittal slices. HCP-style 7T rfMRI data (1.6-mm isotropic
      resolution, 5-fold slice and 2-fold in-plane acceleration, 3600 image volumes and
      ~ 1-h scan) were acquired with pTx and the results were compared to those
      acquired with the original 7T HCP rfMRI protocol. The use of pTx significantly
      improved flip-angle uniformity across the brain, with coefficient of variation
      (i.e., std/mean) of whole-brain flip-angle distribution reduced on average by
      ~39%. This in turn yielded ~17% increase in group temporal SNR (tSNR) as averaged
      across the entire brain and ~10% increase in group functional contrast-to-noise
      ratio (fCNR) as averaged across the grayordinate space (including cortical
      surfaces and subcortical voxels). Furthermore, when placing a seed in either the
      posterior parietal lobe or putamen to estimate seed-based dense connectome, the
      increase in fCNR was observed to translate into stronger correlation of the seed
      with the rest of the grayordinate space. We have demonstrated the utility of pTx
      for slice-accelerated high-resolution whole-brain rfMRI at 7T; as compared to
      current state-of-the-art, the use of pTx improves flip-angle uniformity,
      increases tSNR, enhances fCNR and strengthens functional connectivity estimation.

PMID- 30237035
TI  - Childhood poverty and the organization of structural brain connectome.
AB  - Socioeconomic disadvantage is associated with atypical development in specific
      brain regions, yet the relation between poverty and whole brain network
      organization (i.e., the connectome, a set of brain regions connected with
      neuronal pathways) has not been characterized. Developmental studies indicate
      that the connectome undergoes rapid change during childhood and is consequently
      likely to be highly sensitive to both salutary and detrimental influences. We
      investigated associations between the socioeconomic disparities measured by the
      income-to-needs ratio (INR) in childhood and structural brain network
      organization with 144 healthy children between 6 and 11 years of age (mean age =
      8 years). INR of girls was positively and logarithmically associated with the
      extent to which brain networks were efficiently organized, suggesting that girls
      in more impoverished environments had less efficient brain network organization.
      Lower INR was associated with network inefficiency in multiple cortical regions
      including prefrontal cortex, cingulate, and insula, and in subcortical regions
      including the hippocampus and amygdala. These findings suggest that childhood
      poverty may result in wide-spread disruptions of the brain connectome among
      girls, particularly at the lowest INR levels, and are differentially expressed in
      females and males.

PMID- 30237038
TI  - Emerging microRNAs in cancer diagnosis, progression, and immune surveillance.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that function in post-transcriptional
      regulation of gene expression. Dysregulation of miRNAs has been reported in
      different stages of cancer development and progression. This dysregulation
      results in different miRNA profiles between cancer and normal tissues. Many
      studies have shown a significant correlation between miRNA profile and cancer
      diagnosis and prognosis. Additionally, since a single miRNA regulates multiple
      mRNA targets, miRNAs dysregulation can affect several pathways involved in cancer
      development. Finally, due to their regulatory role in immune cell development,
      many recent studies have reported that certain miRNAs play key roles in cancer
      immunology. In this brief review, we discuss the role of miR-21 and miR-375 in
      the RAS pathway as well as their role in cancer diagnosis and progression, along
      with the role of other select miRNAs in cancer immune surveillance.

PMID- 30237036
TI  - Distinct modes of functional connectivity induced by movie-watching.
AB  - A fundamental question in systems neuroscience is how endogenous neuronal
      activity self-organizes during particular brain states. Recent neuroimaging
      studies have demonstrated systematic relationships between resting-state and task
      induced functional connectivity (FC). In particular, continuous task studies,
      such as movie watching, speak to alterations in coupling among cortical regions
      and enhanced fluctuations in FC compared to the resting-state. This suggests that
      FC may reflect systematic and large-scale reorganization of functionally
      integrated responses while subjects are watching movies. In this study, we
      characterized fluctuations in FC during resting-state and movie-watching
      conditions. We found that the FC patterns induced systematically by movie
      watching can be explained with a single principal component. These condition
      specific FC fluctuations overlapped with inter-subject synchronization patterns
      in occipital and temporal brain regions. However, unlike inter-subject
      synchronization, condition-specific FC patterns were characterized by increased
      correlations within frontal brain regions and reduced correlations between
      frontal-parietal brain regions. We investigated these condition-specific
      functional variations as a shorter time scale, using time-resolved FC. The time
      resolved FC showed condition-specificity over time; notably when subjects watched
      both the same and different movies. To explain self-organisation of global FC
      through the alterations in local dynamics, we used a large-scale computational
      model. We found that condition-specific reorganization of FC could be explained
      by local changes that engendered changes in FC among higher-order association
      regions, mainly in frontal and parietal cortices.

PMID- 30237037
TI  - The importance of surgery in scalp angiosarcomas.
AB  - BACKGROUND: Scalp angiosarcomas (SA) are rare, representing <1% of soft tissue
      sarcomas. The optimal management of these tumors is unknown, with management
      based on small case series. We sought to assess the impact of different therapies
      on overall survival (OS), the practice patterns nationally, and identify factors
      associated with OS for non-metastatic scalp angiosarcomas. METHODS: A
      prospectively maintained database was used to identify non-metastatic scalp
      angiosarcomas who received some form of definitive therapy. Logistics regression,
      Kaplan-Meier, and Cox proportional-hazard models were utilized. RESULTS: A total
      of 589 patients met study entry criteria with a median follow-up of 4.2 years.
      The majority (482 patients, 81.8%) had upfront definitive resection and an
      additional 317 patients (65.8%) received postoperative radiation. Of the 107
      patients who didn't have surgery, the majority (65 patients, 60.7%) received
      definitive radiation and 42 patients (39.3%) received radiation and chemotherapy.
      One-year and five-year survival estimates for patients not receiving definitive
      surgery were 68.0% (95%CI: 57.5-76.4) and 18.0% (95%CI: 10.2-27.5) respectively
      compared to 78.2% (95%CI: 74.0-81.9) and 34.1% (95%CI: 28.9-39.3) for patients
      receiving definitive surgery (p < 0.01). On multivariable analysis, age >=65
      years, tumor size >=5 cm, and not receiving definitive surgery was associated
      with worse OS. CONCLUSIONS: The majority of patients with non-metastatic scalp
      angiosarcomas had upfront definitive surgery, with a subsequent improvement in
      OS, including when accounting for other patient and tumor factors. Postoperative
      radiation was frequently given. Our large series confirmed age and tumor size as
      prognostic factors for this rare disease.

PMID- 30237039
TI  - Optimization of exposure parameters in dental cone beam computed tomography using
      a 3-step approach.
AB  - OBJECTIVE: The aim of this study was to find the optimal balance among tube
      voltage (kV), tube current (mA), and exposure time (s) in cone beam computed
      tomography (CBCT). STUDY DESIGN: Three human hemimandibles were scanned by using
      the 3D Accuitomo 170 scanner (J. Morita, Kyoto, Japan). First, 3 combinations of
      kilovolt (kV) and milliampere (mA) were used at a constant radiation dose. Seven
      observers evaluated the images; the kV of the highest-scoring scan was considered
      optimal. Second, the lowest acceptable mA for visualizing different anatomic
      structures was determined. Finally, the samples were scanned by using 3
      combinations of tube current and exposure time; the observers determined the
      combination with the highest image quality. RESULTS: At a constant radiation
      dose, the highest available voltage (i.e., 90 kV) resulted in the highest image
      quality in terms of general impression, sharpness, noise, and artefacts.
      Depending on the anatomic structure, mA reductions of 20% to 40% compared with
      the default setting were possible. Fast-scan protocols showed equal or slightly
      better image quality compared with the standard-scan mode. CONCLUSIONS: For the
      CBCT model used in this study, optimization implies the use of the highest kV
      along with the shortest exposure time and a task-specific mA. The proposed
      stepwise optimization approach could be applied to any CBCT unit, preferably
      during commissioning.

PMID- 30237040
TI  - The Birth of Red Complex Plastids: One, Three, or Four Times?

PMID- 30237041
TI  - Computed tomography-guided dye localization prior to uniportal thoracoscopic
      surgery for lung nodules: A propensity score matching analysis.
AB  - PURPOSE: Uniportal video-assisted thoracoscopic surgery (VATS) has recently been
      reported as an alternative to conventional VATS. However, preoperative image
      guided localization is usually required for small nodules. The present study
      evaluated the efficacy of preoperative computed tomography-guided dye
      localization prior to uniportal VATS for small undetermined pulmonary nodules.
      METHODS: We retrospectively reviewed 298 consecutive patients who underwent
      uniportal VATS to treat undetermined pulmonary nodules (diameter <= 1.5 cm).
      Propensity score matching incorporating preoperative parameters was used to
      reduce the selection bias in a 1:1 manner. Comprehensive data including clinical
      features and perioperative variables were compared to evaluate the efficacy of
      preoperative computed tomography (CT)-guided dye localization prior to uniportal
      VATS. RESULTS: A total of 232 patients received preoperative CT-guided dye
      localization (localization group) and 66 did not (direct surgery group), and the
      propensity score matching analysis generated 55 pairs of patients in both groups.
      The demographics and operative outcomes, including clinical nodule size, depths
      of the nodule, were comparable for both groups. The complication rates were low
      in both groups (3.6% and 1.8%, respectively). The uniportal to multi-portal VATS
      conversion rate was significantly higher in the direct surgery group than in the
      localization group (12.7% vs 1.8%, P = 0.030). 5 cases were converted due to
      failure in tumor identification (7.3% vs 1.8%, P = 0.182). CONCLUSIONS: Uniportal
      VATS is a feasible, effective, and safe procedure for the treatment of
      undetermined pulmonary nodules. The use of preoperative computed tomography
      guided dye localization may be associated with a lower risk of conversion of
      uniportal VATS.

PMID- 30237042
TI  - Ferrocene-modified iron-based metal-organic frameworks as an enhanced catalyst
      for activating oxone to degrade pollutants in water.
AB  - Ferrocene (Fc) has been regarded as a useful catalyst for activating Oxone to
      generate sulfate radicals (SR) in degradation of organic pollutants.
      Nevertheless, direct usage of Fc molecules in aqueous solutions may lead to
      difficult recovery and aggregation. While a few attempts have immobilized Fc on
      several substrates, these substrates exhibit very low surface areas/porosities
      and, especially, do not offer significantly additional contributions to catalytic
      activities. In this study, a Fe-containing metal organic frameworks (MOFs), MIL
      101, is particularly selected for the first time as a support to immobilize Fc
      chemically. Through the Schiff base reaction, ferrocenecarboxaldehyde can react
      with amine-functionalized MIL-101 (namely, MIL-101-NH2) to form Fc-modified MIL
      101 (Fc-MIL). As Fc-MIL consists of both Fe from MIL-101 and Fc and also exhibits
      high surface areas, it appears as a promising catalyst for activating Oxone.
      Catalytic activities for Oxone activation by Fc-MIL are studied using batch-type
      experiments of amaranth dye degradation. Fc-MIL shows higher catalytic activities
      than its precursor MIL-101-NH2 owing to the modification of Fc, which equips with
      MIL-101 with more catalytic sites for activating Oxone. Besides, Fc-MIL also
      outperforms the benchmark catalyst of Oxone activation, Co3O4, to degrade
      amaranth. In comparison to the other reported catalysts, Fc-MIL shows the much
      smaller activation energy for amaranth degradation, proving its advantage over
      other catalysts. The synthesis technique proposed here can be also employed to
      develop other Fc-modified MOFs for other environmental catalysis applications.

PMID- 30237043
TI  - Structural substitution for SO4 group in tooeleite crystal by As(V) and As(III)
      oxoanions and the environmental implications.
AB  - Two different SO4-free tooeleite were prepared for the first time through
      structural substitution for SO4 group by As(V) and As(III). As(III)-tooeleite and
      As(V)-tooeleite have similar crystalline structure to SO4-tooeleite but
      incorporate different anions in the interlayer space. The removal of As can reach
      94% by forming SO4-free tooeleite crystals, and As leaching in TCLP tests can be
      much lower than that of SO4-tooeleite. Therefore, SO4-free tooeleite crystals are
      of great potential in As removal and immobilization. Moreover, our study
      indicates the different affinities of Fe(III) towards As(III), As(V) and SO4,
      which can explain that a) the coordination structure of As(III)-tooeleite is much
      closer to the ideal crystal structure but easily affected by As(V) and SO4 group;
      b) tooeleite mineral found in natural environments is commonly a SO4-containing
      mineral and associated with scorodite due to the abundance of As(V) and SO4
      group.

PMID- 30237044
TI  - Effects of virgin microplastics on goldfish (Carassius auratus).
AB  - Microplastics (MPs) are abundant in freshwater and marine environments. They are
      diverse shape and size and are ingested by organisms. In this study, goldfish
      (Carassius auratus) were exposed via diet to three types of virgin MPs material
      types and shapes including fibers, fragments, and pellets. After six weeks of
      exposure, various sub-lethal effects, but no mortality, was observed. Fish
      exposed to plastic showed significant weight loss compared with the control.
      Fibers were found in the gills, gastrointestinal tract (GIT), and feces were not
      likely to accumulate in the GIT. Pronounced and severe alterations were found in
      the livers of fish exposed to fibers. The distal intestine showed more pronounced
      and severe changes compared to the proximal intestine, likely due to an intake of
      fibers. The ingestion of fibers caused the highest frequencies of progressive and
      inflammatory changes in the livers and intestines. This is in accordance with the
      higher organ index in these organs compared to other texa. Conversely, fragments
      and pellets were not ingested but chewed and expelled. Chewing process resulted
      in damages to the jaws as ranging from slight exfoliation to deep incisions. The
      highest frequency of regressive and circulatory (e.g., dilated sinusoids) changes
      was found in fish exposed to fragments, specifically in the upper and lower jaw,
      and in lower jaw and liver, respectively. Together, these results demonstrate
      that ingestion and chewing of MPs lead to damages in various organs and tissues
      of the gastrointestinal system, and suggest that different materials can have
      drastically different impacts on fish.

PMID- 30237045
TI  - Employee safety single vs. dual priorities: When is the rate of work-related
      driving accidents lower?
AB  - Applying both occupational safety and ambidexterity theories, we investigate
      which situation in organizations leads to a lower number of work-related road
      accidents: a single-priority situation focused on road safety, or a dual-priority
      situation in which both road safety and customer service are priorities.
      Occupational safety theory puts forward an 'either-or' approach in which employee
      safety must be the first priority, above and beyond all others. In contrast, the
      ambidexterity theory's 'both-and' approach suggests a simultaneous coexistence of
      priorities. Results from forty-three units in three organizations that make
      intensive use of work-related driving and aim to deliver good customer service
      are described. The results suggest that when the level of customer service
      priority was low, an increase in the level of road safety priority significantly
      decreased the number of road accidents. However, when the level of customer
      service priority was high, an increase in the level of road safety priority was
      not associated with less road accidents. The results show that work-related road
      accidents would be lower in a safety-first, single-priority situation compared to
      a dual-priority situation encompassing both road safety and customer service. We
      discuss the theoretical and practical implications of these results.

PMID- 30237046
TI  - The effect of gender, occupation and experience on behavior while driving on a
      freeway deceleration lane based on field operational test data.
AB  - Deceleration lanes improve traffic flow by reducing interference, increasing
      capacity and enhancing safety. However, accident rates are higher on these
      interchange segments than on other freeway segments. It is important to attempt
      to reduce traffic accidents on these interchange segments by further exploring
      the behavior of different types of drivers on a highway deceleration lane. In
      this study, with field operational test (FOT) data from 89 driving instances
      (derived from 46 participants driving the test road twice) on a typical freeway
      deceleration lane, section speed profiles, vehicle trajectories, lane position
      and other key parameters were obtained. The lane-change characteristics and speed
      profiles of drivers with different genders, occupations and experiences were
      analyzed. The significant disparities between them reflects the risk associated
      with different groups of drivers. The study shows that male drivers changed to
      the outside lane earlier; professional drivers and experienced drivers made the
      last lane change as early as possible to enter the deceleration lane; and the
      speed of the vehicles entering the exit ramp was significantly higher than the
      speed limit. This research work provides ground truth data for deceleration lane
      design, driver ability training and off-ramp traffic safety management.

PMID- 30237047
TI  - The relationship between the demographic, personal, and social factors of
      Malaysian motorcyclists and risk taking behavior at signalized intersections.
AB  - In the context of road safety, risk-taking is undoubtedly one of the main
      contributory factors in road accidents. The actual forces which influence
      individuals to take such risks, nevertheless, are still not fully understood. To
      address this, this study was therefore conducted to investigate the relationship
      of the demographic, personal, and social factors of motorcyclists, with a
      specific focus on their risk-taking behavior at signalized intersections in
      Malaysia. This study adopted the quantitative method using cross-sectional
      questionnaire surveys and involved 251 respondents. The demographic factors were
      analyzed using the t-test and an ANOVA Scheffe Post-Hoc test, while the
      motorcyclists' personal and social characteristics were analyzed with multiple
      linear regression. The findings indicate that the individuals who were greater
      risk takers at signalized intersections were teenage motorcyclists (16-25 years
      old) who had finished their education before taking their high school diploma,
      and who also received a lower than average monthly income from private sector
      firms. The actual experience of accidents was also shown to be positively related
      to this risk-taking behavior. In addition, in term of personal and social
      factors, results showed that, for these individuals, there was a significant
      difference between the strength of peer influence and that of parental and spouse
      guidance. However, there was no significant difference in the risk-taking
      behavior of Malaysian motorcyclists riding at signalized intersections for the
      following factors: between genders, in terms of accident involvement, in terms of
      enforcement of traffic regulations, and prevention steps and confidence level
      after being involved in an accident.

PMID- 30237048
TI  - Identification and characterization of microRNAs in a cestode Hydatigera
      taeniaeformis using deep sequencing approach.
AB  - Hydatigera taeniaeformis (formerly known as Taenia taeniaeformis) is a parasitic
      tapeworm that has a worldwide distribution. H. taeniaeformis is naturally
      transmitted between mice and cats and threatens to human health, especially those
      who are in close contact with pets. MicroRNAs (miRNAs) are a class of small
      regulatory non-coding RNAs involved in the regulation of parasite growth and
      development, parasite infection and immunology, and host-pathogen interactions.
      The miRNA profile of H. taeniaeformis remains to be elucidated. Herein, 47
      conserved miRNAs (grouped into 34 miRNA families) and 4 novel miRNAs were
      identified in H. taeniaeformis metacestodes using deep sequencing approach. Among
      them, hta-miR-71, -let-7, and-miR-87 was absolutely predominant in H.
      taeniaeformis metacestodes. Moreover, comparative analysis revealed the presence
      of miR-71/2 and miR-4989/277 clusters in H. taeniaeformis. Nucleotide bias
      analysis of identified miRNAs showed that the adenine (A) was the dominant
      nucleotide at the beginning of the miRNAs, particularly at the positions of third
      and 7th nucleotides. The study provides rich data for further understandings of
      H. taeniaeformis biology.

PMID- 30237049
TI  - Effective eradication of pinworms (Syphacia obvelata and Aspiculuris tetraptera)
      with Polygonum cognatum Meissn.
AB  - Polygonum cognatum Meissn. (Polygonaceae) is a wild edible plant known locally as
      "solucanotu, madimak" in Turkey and it has been used for various purposes, such
      as diuretic and antidiabetic, as well to treat oxyuris and worms internally in
      humans. The present study was carried out to investigate the anthelmintic
      activity of various extracts were obtained from the aerial parts of P. cognatum
      in order to justify its traditional usage in Turkish folk medicine. n-Hexane,
      ethyl acetate and methanol extracts were prepared from the aerial parts of the
      plant, successively. The anthelmintic potentials of these extracts were evaluated
      on mice naturally infected with Syphacia obvelata and Aspiculuris tetraptera.
      Cellophane perianal tape test and fecal flotation test were used for the activity
      screening. The results were compared with control and reference groups. In
      addition to all these experiments, the total amount of phenolic compounds and
      tannin contents thought to be responsible for the activity were evaluated for all
      extracts. According to the results, it has been found that the methanolic extract
      reduced the number of S. obvelata (66.8%) and A. tetraptera (73.4%) eggs.
      Moreover, the methanolic extract include higher amount of total phenolic compound
      (48.75 +/- 0.82 mg of GA/g of extract) and tannin (30.04 +/- 0.22 mg TA/g of
      extract) than n-Hexane (17.21 +/- 0.75 mg of GA/g of extract; 6.82 +/- 0.41 mg
      TA/g of extract) and ethyl acetate (25.06 +/- 0.94 mg of GA/g of extract; 10.29
      +/- 0.34 mg TA/g of extract); therefore the anthelmintic activity could be
      related to these constituents. The present study explored the anthelmintic
      potential of P. cognatum. Further studies should be conducted into the mechanism
      of these compounds' against helminths. This study can be an important step in the
      discovery of new anthelmintic agents.

PMID- 30237050
TI  - DNA damage induced by metronidazole in Giardia duodenalis triggers a DNA
      homologous recombination response.
AB  - The mechanisms underlying metronidazole (MTZ) resistance in Giardia duodenalis
      have been associated with decreased activity of the enzymes implicated in its
      activation including nitroductase-1, thioredoxin reductase and pyruvate
      ferredoxin oxidoreductase (PFOR). MTZ activation generates radicals that can form
      adducts with proteins such as thioredoxin reductase and alpha- and -beta giardins
      as well as DNA damage resulting in trophozoite's death. The damage induced in DNA
      requires a straight forward response that may allow parasite survival. Here, we
      studied changes in histone H2A phosphorylation to evaluate the DNA repair
      response pathway after induction of double strand break (DSB) by MTZ in Giardia
      DNA. Our results showed that the DNA repair mechanisms after exposure of Giardia
      trophozoites to MTZ, involved a homologous recombination pathway. We observed a
      significant increase in the expression level of proteins GdDMC1B, which carries
      out Rad51 role in G. duodenalis, and GdMre11, after 12 h of exposure to 3.2 MUM
      MTZ. This increase was concomitant with the generation of DSB in the DNA of
      trophozoites treated MTZ. Altogether, these results suggest that MTZ-induced DNA
      damage in Giardia triggers the DNA homologous recombination repair (DHRR)
      pathway, which may contribute to the parasite survival in the presence of MTZ.

PMID- 30237051
TI  - Reduction of bovine strongilides in naturally contaminated pastures in the
      southeast region of Brazil.
AB  - Biological control through the use of nematophagous fungi is a sustainable
      alternative for combatting helminthes in domestic animals and allows a reduction
      in the use of anthelmintics. The objective of this research was to evaluate the
      efficacy of the Arthrobotrys cladodes var macroides fungus in a pelleted
      formulation, based on sodium alginate and administered twice a week orally, as an
      alternative for the biological control of nematodes in field-grown young cattle.
      The experiment was conducted in a farm located in the municipality of Vicosa, MG,
      where 12 cattle, seven to nine months old, were allocated in two groups (treated
      group and control group) and distributed in pickets of Brachiaria decumbens,
      naturally infested with nematode larvae. The animals in the treated group
      received 1g of sodium alginate matrix pellets for every 10 kg of animal live
      weight, containing the nematophagous fungus Arthrobotrys cladodes var macroides
      and administered twice a week in conjunction with commercial feed. In the control
      group, each animal received 1 g of pellets for every 10 kg of animal live weight,
      without fungal mycelium added to the feed. Samples of feces and pastures were
      collected fortnightly for 12 months. The results showed that the most prevalent
      nematode genera in the coprocultures were Haemonchus sp., Cooperia sp. and
      Oesophagostomum sp., reflecting the results found in forage. The pasture that
      contained the animals that received feed with the fungus presented a reduction of
      59% and 52% of larvae recovered at distances of 20 cm and 40 cm from the fecal
      pats, respectively. The mean number of eggs per gram of feces each month and
      animal body weight did not differ (p > 0.05) between the treated and control
      groups. Stool and soil samples from both groups were colonized by A. cladodes
      fungus and other fungi. Administration of Arthrobotrys cladodes var macroides
      mycelium by means of a sodium alginate matrix twice weekly reduced larval
      infestation of the surrounding pasture, indicating that this fungus may be a
      promising biological control of infecting forms of nematodes present in the
      environment.

PMID- 30237052
TI  - Efficacy of chitosan, a natural polysaccharide, against Cryptosporidium parvum in
      vitro and in vivo in neonatal mice.
AB  - Cryptosporidiosis is a zoonotic disease caused by species in the genus
      Cryptosporidium. In young ruminants, Cryptosporidium parvum causes economically
      significant disease with mild to severe clinical signs and occasional death. The
      typical clinical course in animals aged 1-3 weeks old is acute diarrhoea.
      Currently there are no available treatments that are fully effective against
      cryptosporidiosis in either humans or animals. Therefore there is a critical need
      for the development of new therapeutic agents. We adapted two in vitro culture
      systems (HCT-8 and Caco-2 cell lines) for C. parvum infection to investigate the
      "anticryptosporidial" activity of two chitosans; Chitosan NAG and Chitosan Mix.
      Chitosan-a naturally-occurring polysaccharide compound-has been found to be
      active against a variety of diseases, possessing both antimicrobial and
      anticancer properties. We investigated both chitosan's toxicity and effects on C.
      parvum in the two in vitro models. To evaluate chitosan's effects on oocyst
      shedding in vivo, CD-1 neonate mice were orally inoculated with C. parvum oocysts
      (Iowa strain), treated with chitosan, and compared to infected non-treated
      animals. Paromomycin, a classical drug used in veterinary medicine, was used as a
      reference compound. Immunofluorescence techniques were used to analyse the
      parasites. Our results showed significant reductions in Cryptosporidium oocyst
      viability (>95%) after oocyst pre-incubation with either paromomycin (P < 0.001),
      Chitosan Mix or Chitosan NAG (P < 0.001), for 24 h at 37  degrees C.
      Additionally, paromomycin, Chitosan Mix, and Chitosan NAG significantly inhibited
      C. parvum multiplication in HCT-8 and Caco-2 cell lines (P < 0.005). These
      effects were dose-dependent. In in vivo studies, treatment with both chitosans
      (Chitosan NAG, Chitosan Mix) or paromomycin sulfate significantly reduced
      parasite shedding in infected treated newborn mice (-56%, -34.5% and -58%,
      respectively). In conclusion, these findings provide the first in vitro and in
      vivo evidence of the anticryptosporidial activities of this natural
      polysaccharide.

PMID- 30237053
TI  - Frequent issues and lessons learned from EuroFlow QA.
AB  - EuroFlow Quality Assessment was designed to provide a feedback on the quality of
      the standardization effort in executing the EuroFlow protocols for sample
      preparation and instrument setup. It was first beta-tested by the members of the
      EuroFlow consortium internally (2010-2013) and opened to the external
      participants from 2015 onwards. The goal of participation in the EuroFlow QA is
      to evaluate whether the technical quality of the data generated by the laboratory
      is comparable to the data of the EuroFlow members and thus if a non-EuroFlow
      member participant can use the EuroFlow reference sample database for his own
      patient evaluation. Also it assesses whether data are sufficiently standardized
      for automated population gating and alarm notification. By spring 2018, a total
      87 laboratories from 32 countries on five continents have registered for the
      EuroFlow QA program. We evaluated 163 results of 2015-2016 QA rounds, where we
      noted clear improvement in the score of first-time participants (median score of
      91% correct) when they participated second time or later (median score of 94%
      correct, p = 0,017), which was comparable to EuroFlow member scores (median score
      of 97% correct). Among frequent mistakes, we found non-adherence to the EuroFlow
      protocols (improper reagent used), improper gating and some compensation issues.
      In summary, we show that EuroFlow QA has a positive impact on improvement of
      standardized data quality of non-member laboratories adhering to the EuroFlow
      standard operating procedures and reagent panels.

PMID- 30237054
TI  - Comparison of three immunoassays for determination of immunity to rubella virus
      in healthcare workers.
AB  - Rubella virus is a critical infectious pathogen to healthcare workers but is
      preventable by vaccination. In this study, we used three immunoassays - LIAISON
      Rubella IgG, ARCHITECT Rubella IgG, and AtheNA Multi-Lyte MMRV IgG - to detect
      rubella virus IgG and tested 182 serum specimens. The percentage of positives
      with the three Rubella tests were as follows: LIAISON, 71.9%; ARCHITECT, 83.5%;
      and AtheNA, 99.5%. The three assays showed an overall agreement rate of 71.9%.
      The rates of seropositive detection with LIAISON, ARCHITECT, and AtheNA among
      healthcare workers with and without self-reporting history of past infection or
      vaccination were 70.7% and 90.9%, 83.6% and 81.8%, and 99.4% and 100%,
      respectively. The three immunoassays showed a low agreement rate for rubella
      virus IgG. Therefore, choosing accurate and appropriate IgG assay methods is very
      important for effective infection control and prevention.

PMID- 30237055
TI  - Shared social identity in leadership.
AB  - In this paper we review recent evidence on the social identity model of
      leadership. First, we explain how this model is rooted in the social identity
      approach in social psychology and, specifically, the notion that shared reality
      and joint action in groups derives from shared social identity. We then show how
      effective leadership is a process of social identity management and we examine
      both the antecedents, the psychological and the political consequences of
      managing social identities.

PMID- 30237056
TI  - Conservative management of anterior cruciate ligament injury in paediatric
      population: About 53 patients.
AB  - INTRODUCTION: The last symposium held by the French Arthroscopy Society was on
      anterior cruciate ligament (ACL) reconstruction on children. The first aim of
      this study was to analyse the tolerance of conservative management of ACL rupture
      in children. We also tried to find predictive factors of ACL reconstruction.
      MATERIAL AND METHODS: We conducted an observational, retrospective study in an
      academic department of paediatric orthopaedic surgery. All patients under the age
      of eighteen, who were treated conservatively for an acute intra-ligamentous ACL
      rupture confirmed by magnetic resonance imaging (MRI) between 2007 and 2017, were
      included. Two groups were analysed: operated patients and conservative treatment.
      We also analysed population according Tanner stage. RESULTS: Fifty-three patients
      were included in this study. The median length of follow-up was 31.5 months
      [interquartile range (IQR): 22.3-49.3]. The median age at the last follow-up was
      14.4 years [IQR: 12.6-15.5]. All patients were allowed to practice activities
      without restrictions, including pivoting sports. Tegner activity level scale
      remains identical before injury and at last follow-up (p: n.s.). Nineteen
      patients (36%) described knee instability at last follow-up. On the last MRI, 9
      (17%) patients had meniscal tears but only one patient (2%) needed a menisectomy.
      Twenty-one patients (40%) underwent ACL reconstruction. The 4-years successful
      conservative treatment rate was 92% (95% CI: 85-98%). Clinical instability at
      first examination was the only significant predictive factors of bad tolerance of
      conservative management (p=0.047). DISCUSSION: Conservative management of ACL
      rupture in paediatric population is a valuable treatment which permits return to
      a normal life with sports activities without major increasing of meniscal tears.
      The rehabilitation protocol must restore full knee stability to permit a
      successful conservative treatment. We must study the impact of pubertal status on
      larger group. LEVEL OF EVIDENCE: IV, retrospective study.

PMID- 30237058
TI  - Description of low back pain clinical trials in physical therapy: a cross
      sectional study.
AB  - OBJECTIVE: To describe the main characteristics of low back pain randomized
      controlled trials on the Physiotherapy Evidence Database, and to rank the
      journals where these trials were published according to their Impact Factor.
      METHODS: This is a cross sectional study based on a collection of randomized
      controlled trials. A random sample of 200 low back pain trials published between
      2010 and 2015 were selected from Physiotherapy Evidence Database in February
      2016. We collected the following main characteristics of trials: 2015 journal
      Impact Factor; if the paper was published as open access; CONSORT recommendations
      endorsement by the journal; methodological quality and statistical reporting
      measured by the 0-10 items Physiotherapy Evidence Database scale. Data was
      analyzed descriptively. RESULTS: Trials were published in journals with a mean
      Impact Factor of 2.5 (SD 2.5), from which 55.5% endorsed the CONSORT
      recommendations. The methodological quality was moderate with 5.8 points (SD
      1.6). The top 3 journals according to Impact Factor were: (1) British Medical
      Journal; (2) Annals of Internal Medicine; and (3) BMC Medicine. Only 6 out of 97
      journals publishing low back pain trials combined the following factors: journal
      Impact Factor higher than 2.0, mean trial methodological quality higher than 6.0
      points, endorse CONSORT recommendations and offering papers as open access.
      CONCLUSION: Clinicians interested in low back pain trials must look for a wide
      variety of healthcare journals. A substantial number of low back pain randomized
      controlled trials did not follow adequate reporting and methodological
      recommendations.

PMID- 30237057
TI  - Opinion of the scientific committee on consumer safety (SCCS) - Opinion on the
      safety of cosmetic ingredient phenylene bis-diphenyltriazine (CAS No 55514-22-2) 
      S86.

PMID- 30237059
TI  - Culturally sensitive communication at the end-of-life in the intensive care unit:
      A systematic review.
AB  - OBJECTIVES: The objectives of this systematic review were the following: (i) to
      describe whether culturally sensitive communication is used by clinicians (nurses
      and physicians) when communicating with patients and families at the end-of-life
      in the intensive care unit and (ii) to evaluate the impact of culturally
      sensitive communication at the end-of-life. The systematic review question was
      how is culturally sensitive communication used by clinicians when communicating
      with patients and families at the end-of-life in the intensive care unit? DATA
      SOURCES: A search of CINAHL, MEDLINE, Embase, and PsycINFO databases identified
      all peer-reviewed research evidence published in English between January 1994 and
      November 2017. Two authors independently assessed articles for inclusion. From
      the 124 articles resulting from the search, nine were included in this systematic
      review. REVIEW METHODS: Articles were independently assessed for quality by two
      authors using Caldwell et al.'s framework to critique health research. The data
      available in this systematic review were heterogeneous, with varied study designs
      and outcome measures, making the data unsuitable for meta-analysis. The most
      appropriate method for data synthesis for this systematic review was narrative
      synthesis. RESULTS: From the narrative synthesis, two major themes emerged:
      communication barriers and cultural and personal influences on culturally
      sensitive communication. Communication barriers were identified in eight studies,
      influencing the timing and quality of culturally sensitive communication at the
      end-of-life. Cultural and personal influences on communication at the end-of-life
      was present in eight studies. CONCLUSIONS: The findings of this systematic review
      show that clinicians lack the knowledge to enable effective interaction with
      culturally diverse patients and families at the end-of-life.

PMID- 30237060
TI  - Association of dispatcher-assisted bystander cardiopulmonary resuscitation with
      survival outcomes after pediatric out-of-hospital cardiac arrest by community
      property value.
AB  - OBJECTIVE: We aimed to demonstrate the association of bystander cardiopulmonary
      resuscitation (BCPR) with survival outcomes after pediatric out-of-hospital
      cardiac arrest (OHCA) by community property value groups. METHODS: This
      observational study enrolled all emergency medical services (EMS)-treated
      pediatric OHCAs in Korea between 2012 and 2015. Enrolled patients were divided
      into three groups: BCPR with dispatcher-assistance (DA), BCRP-without-DA, and no
      BCPR. Patients were categorized based on tertiles for property tax per capita of
      community in which the cardiac arrest occurred. The endpoint was survival to
      discharge. To test the interactive effects between BCPR and community property
      value on study endpoints, a multilevel logistic regression model with an
      interaction term was used. RESULTS: A total of 2020 patients were enrolled (37.0%
      BCPR-with-DA, 14.5% BCPR-without-DA, and 48.5% no-BCPR). BCPR-with-DA and BCPR
      without-DA were more likely to have higher rates of survival to discharge
      compared to no-BCPR (8.6% and 13.0% vs. 3.5%; AORs (95% CIs): 2.23 (1.33-3.74)
      and 2.87 (1.57-5.25)). By interaction analysis with community property tax per
      capita, the AORs for survival in BCPR-with-DA and BCPR-without-DA groups were
      2.56 (1.03-6.38) and 3.48 (1.10-10.9) for high value communities, 2.25 (0.95
      5.31) and 3.76 (1.53-9.23) in middle communities, and 1.88 (0.88-3.99) and 1.54
      (0.57-4.17) in low value communities (interaction, p = 0.68). CONCLUSION: In
      pediatric OHCAs, BCRP was associated with improved survival outcomes. The
      survival benefits of BCPR did not differ significantly by community property
      value.

PMID- 30237061
TI  - The roles of breast cancer resistance protein (BCRP/ABCG2) and multidrug
      resistance-associated proteins (MRPs/ABCCs) in the excretion of cycloicaritin-3-O
      glucoronide in UGT1A1-overexpressing HeLa cells.
AB  - Cycloicaritin is a bioactive natural phenolic compound from Epimedium species.
      However, the glucuronidation and excretion which would influence oral
      bioavailability and pharmacokinetics of cycloicaritin still remain unknown. Here
      we aimed to establish UGT1A1 stably transfected HeLa cells, and to determine the
      contributions of BCRP and MRPs transporters to excretion of cycloicaritin-3-O
      glucuronide. First, beta-estradiol was used to validate the expression of active
      UGT1A1 protein in engineered HeLa1A1 cells. Furthermore, Ko143 (5 and 20 MUM) led
      to a significant decrease (42.4%-63.8%, p < 0.01) in CICT-3-G excretion and
      obvious accumulation (19.7%-54.2%, p < 0.05) of intracellular CICT-3-G, while
      MK571 (5 and 20 MUM) caused a significant reduction (46.8%-64.8%, p < 0.05) in
      the excretion and obvious elevation (50.7%-85.2%, p < 0.01) of intracellular
      level of CICT-3-G. Furthermore, BCRP knocked-down brought marked reduction in
      excretion rates of CICT-3-G (26.0%-42.2%, p < 0.01), whereas MRP1 and MRP4
      mediated silencing led to significant decrease in the excretion of CICT-3-G
      (23.8%-35.4%, p < 0.05 for MRP1 and 11.9%-16.0%, p < 0.05 for MRP4). By contrast,
      neither CICT-3-G excretion nor CICT-3-G accumulation altered in MRP3 knocked-down
      cells as compared to scramble cells. Taken together, BCRP, MRP1 and MRP4 were
      identified as the most important contributors for CICT-3-G excretion. Meanwhile,
      the UGT1A1 modified HeLa cells were a simple and practical tool to study UGT1A1
      mediated glucuronidation and to characterize BCRP and MRPs-mediated glucuronide
      transport at a cellular level.

PMID- 30237062
TI  - GADD45beta-I attenuates oxidative stress and apoptosis via Sirt3-mediated
      inhibition of ER stress in osteoarthritis chondrocytes.
AB  - Osteoarthritis (OA) is one of the most characterized joint diseases associated
      with chondrocyte apoptosis. JNK plays an important role in apoptosis in many
      pathological conditions, but systemic inhibition of JNK was shown to result in
      detrimental side effects. MAPK kinase 7 (MKK7) is a direct upstream kinase that
      regulates JNK and has been shown to activate JNK specifically under toxic
      conditions. In this study, we investigated the effect of GADD45beta-I, a cell
      permeable inhibitor targeted for MKK7, on IL-1beta-induced cytotoxicity in rat
      chondrocytes. The results showed that IL-1beta exposure resulted in toxicity in a
      dose-dependent manner, which was nullified by endoplasmic reticulum (ER) stress
      inhibitors. GADD45beta-I significantly preserved cell survival, inhibited
      oxidative injury and reduced apoptosis after IL-1beta treatment. ER stress in
      chondrocytes was attenuated by GADD45beta-I, as evidenced by reduced levels of
      GRP78 and CHOP, as well as decreased caspase-12 cleavage. In addition, GADD45beta
      I increased the enzymatic activities of mitochondrial antioxidant enzymes,
      including IDH2, GSH-Px and SOD2. GADD45beta-I significantly upregulated the
      expression of Sirt3 and attenuated IL-1beta-induced acetylation of SOD2.
      Furthermore, GADD45beta-I-induced inhibition of ER stress and protection in
      chondrocytes were partially reversed by knockdown of Sirt3. In conclusion, our
      data indicated that GADD45beta-I protected chondrocytes against IL-1beta through
      Sirt3-mediated inhibition of ER stress. Targeting MKK7 might be an ideal
      therapeutic strategy for reducing chondrocyte apoptosis in OA.

PMID- 30237063
TI  - Dual-layer detector CT of chest, abdomen, and pelvis with a one-third iodine
      dose: image quality, radiation dose, and optimal monoenergetic settings.
AB  - AIM: To compare the image quality and radiation dose of reduced iodine dose dual
      layer detector (DL) computed tomography (CT) with those of a conventional 120 kVp
      protocol for chest-abdomen-pelvis CT (CAP-CT). MATERIALS AND METHODS: Forty
      patients with renal dysfunction (estimated glomerular filtrating ratio <45
      ml/min/1.73 m2) underwent reduced iodine dose CAP-CT (120 kVp, 200 mg iodine/kg)
      on DLCT. Virtual monochromatic images (VMI) at 40-70 keV (5 keV interval) were
      reconstructed retrospectively. Forty matched patients who underwent conventional
      CAP-CT (120 kVp, 600 mg iodine/kg, iterative reconstruction) were included as
      controls. The size-specific dose estimate (SSDE), image noise, CT attenuation,
      and contrast-to-noise ratio (CNR) were compared between the protocols. Two
      radiologists rated image contrast, image noise, streak artefact, and diagnostic
      confidence on a five-point scale. RESULTS: The SSDE of the DLCT group was
      approximately 20% lower than that of the 120 kVp group (15.4+/-1.9 versus 19.4+/
      2.3 mGy, p<0.01). DLCT-VMI provided almost constant image noise throughout the
      range of energies (differences of <=13%), with the noise being equivalent or
      lower than 120 kVp in the abdomen. CT attenuation and CNR gradually increased as
      the energy decreased, with values comparable to 120 kVp being attained at around
      45-50 keV. Although streak artefact was accentuated at 40-50 keV (p<0.01), the
      highest scores for diagnostic confidence were assigned at 40 and 45 keV, both of
      which were equivalent to 120 kVp (p=1.0). CONCLUSION: For CAP-CT with a one-third
      iodine dose, DLCT-VMI at 40-45 keV allows for a 20% reduction in radiation dose,
      while preserving image quality comparable to that of conventional 120 kVp
      protocol.

PMID- 30237064
TI  - Air test as a simple method of screening for Hirschsprung's disease.
AB  - AIM: To present the technique and the diagnostic accuracy of the air test to
      diagnose Hirschsprung's disease (HD). MATERIALS AND METHODS: Children who
      attended hospital for chronic constipation (CC) between January 2012 and December
      2016 for whom the air test was performed were enrolled. The test was conducted
      during contrast enema under fluoroscopic observation using 20-50 ml injections of
      air into the rectum through a 10 F Nelaton catheter. The demographics, results of
      the air test, and additional examinations, as well as the outcomes of subsequent
      treatments were analysed retrospectively. RESULTS: The air test was conducted in
      179 patients (median: 3 years, range: 0-14 years), and was positive in 150 and
      negative in 29 cases. Of the 29 patients with negative results, four were
      diagnosed with HD by rectal suction biopsy (RSB). Of the remaining 25 patients,
      RSB was conducted in seven and HD was excluded in all cases. In all 150 patients
      with positive air test results, CC was adequately controlled with conservative
      treatment. The sensitivity and specificity of the air test were 100% (4/4) and
      85.7% (150/175), respectively. CONCLUSIONS: The air test can be used as a new non
      invasive screening method for HD, performed simultaneously with contrast enema.

PMID- 30237065
TI  - Re: Radiology-led Lung cancer escalation pathway: a streamlined innovative
      service.

PMID- 30237066
TI  - Automation and assessment of de novo modeling with Pathwalking in near atomic
      resolution cryoEM density maps.
AB  - With the rapidly growing number of macromolecular structures solved to near
      atomic resolution using electron cryomicroscopy (cryoEM), map interpretation and
      model building directly from the density without the use of structural templates
      has become increasingly important. As part of the 2015/2016 Map and Model
      Challenge, we attempted to assess our latest de novo modeling tool, Pathwalking,
      in terms of performance and usability, as well as identify areas for future
      improvements. In total, we applied Pathwalking to six density maps between 3 and
      4.5 A resolution selected from the challenge data sets. In five of the six cases,
      Pathwalking was able to accurately determine the protein fold and in three of
      these cases, the final all atom model had less than 1.6 A RMSD when compared to
      the known structure. Model building and refinement was nearly completely
      automated, used default parameters and took less than 30 min to complete a
      refined all atom model. A direct outgrowth of this work was a more streamlined
      automated command line Pathwalking utility, as well as a novel sequence
      assignment and optimization routine, which attempts to register sidechain density
      with expected side chain volume. In total, Pathwalking offers a nearly complete,
      robust and efficient method for constructing atomistic protein structures
      directly from a density map without the aid of a template.

PMID- 30237067
TI  - [Management of vesicourethral anastomotic stenosis after radical prostatectomy].
AB  - Vesicourethral anastomotic stenosis is a relatively uncommon problem after
      radical prostatectomy, but it could become recurrent and difficult to treat. Risk
      factors are known, and they can help to decrease the incidence. When discussing
      the therapeutic plan, we must consider the stenosis risk, and also the urinary
      continence after the prostatectomy. Many treatment schedules are proposed, some
      of them with low available evidence, limited to case series with different number
      of patient and follow-up length, or reviews on the subject. Endoscopic options
      are the commonest, obtaining different success rates depending on the incision,
      resection or vaporization of the tissue. They could also benefit from the use of
      adjuvant local injections of drugs regulating tissue growth. Recurrent or
      obliterated cases could require surgical reconstruction using perineal, abdominal
      or combined approaches, or even suprapubic urinary diversions.

PMID- 30237068
TI  - The impact of thoracotomy on psychological and sexual function in men with lung
      cancer.
AB  - OBJECTIVE: We aimed to investigate the effect of major thoracic surgery on sexual
      functions and psychogenic aspects of men who underwent surgery for lung cancer.
      MATERIAL AND METHODS: This study was conducted to assess depression and erectile
      function in patients who underwent surgical treatment for lung cancer. The data
      of 50 patients in the study group, and 39 participants in the control group who
      met the criteria were analyzed. Erectile dysfunction (ED) and symptoms of
      depression were assessed in patients before and three months after surgery.
      RESULTS: The mean ages were 58.4+/-11.6 and 61.3+/-6.9 years; the mean BMIs were
      25.6+/-4.3kg/m2 and 24.8+/-5.7kg/m2; the mean forced vital capacities (FVC) were
      3.1+/-0.6L and 3.4+/-1.4L; the mean FEV1/FVC were 86.1+/-10.3 and 80.3+/-4.1; the
      mean Beck Depression Inventory scores were 9.3+/-6.9 and 6.0+/-6.2, and the mean
      FVC% were 82.9+/-14.9 and 82.0+/-26.2 for the study and control groups,
      respectively. The mean preoperative International Index of Erectile Function
      (IIEF-5) scores were 14.1+/-4.1 and 10.8+/-4.7 postoperative in the study group,
      and 17.4+/-8.6 in the control group. The logistic regression analysis showed that
      postoperative complications resulted in a 3.95-times higher risk of suffering
      from ED. CONCLUSION: Our study supported that surgical treatment of lung cancer
      adversely affected psychogenic status and sexual function due to its stringent
      nature. The fear of death affects the quality of life and the psychogenic aspect
      of the patients with lung cancer. Clinicians should thoroughly inform the
      patients about sexual dysfunction and psychogenic disorders, and when needed
      providing an appropriate sexual counseling and treatment is necessary. Good
      communication contributes to a better quality of life.

PMID- 30237069
TI  - Next generation sequencing for diagnosis of severe pneumonia: China, 2010-2018.

PMID- 30237070
TI  - Academic success of undergraduate nursing students.
AB  - Defining students' academic success can be challenging when perceptions about the
      qualities that define it differ. Little is known about these perceptions when it
      comes to nursing students and particularly when English is a second language
      (ESL). Larger numbers of international and ESL students are gaining entrance into
      nursing education programs. The study purpose was to identify ways undergraduate
      nursing students and particularly ESL students self-report academic success.
      Study findings showed statistically significant findings for perceived student
      success when students had a prior degree, they were at a higher academic course
      level in their program, and believed they communicated adequately. Faculty roles
      that affect students' perceptions of their academic success are described and
      areas where actions can be taken are suggested.

PMID- 30237071
TI  - Reasonable adjustments for everyone: Exploring a paradigm change for nurse
      educators.
AB  - The number of students with learning difficulties enrolled in nursing programs
      has increased. Under the current educational paradigm, nurse educators grant
      requests for reasonable adjustments from students with diverse learning needs in
      an attempt to promote equity and inclusivity in nursing programs. This system has
      fundamental flaws which reduce its effectiveness and perpetuates the differences
      between students with learning difficulties and their peers. A new educational
      paradigm based on Universal Design principles is proposed. Comparisons are made
      between Universal Design classroom teaching and management strategies and current
      evidence-based pedagogy. The first steps toward adopting a new paradigm are
      discussed and examples offered. Reasonable adjustments which support the diverse
      learning needs of all students are feasible and practical. This paradigm change
      can be implemented by individual nurse educators or as a campus-wide initiative.

PMID- 30237072
TI  - Widespread occurrence of squirrel adenovirus 1 in red and grey squirrels in
      Scotland detected by a novel real-time PCR assay.
AB  - The Eurasian Red Squirrel (Sciurus vulgaris) is distributed throughout large
      parts of Europe and Asia. However, its distribution in certain regions of Europe
      is endangered by the invasive, non-native Grey Squirrel (Sciurus carolinensis).
      Adenoviruses were already described in squirrels in Great Britain almost two
      decades ago. In 2013, a squirrel adenovirus (SqAdV-1) was additionally found in a
      red squirrel from Germany, which suffered from acute diffuse catarrhal enteritis,
      and the complete genome sequence was determined. Here, samples from dead red (n =
      25) and grey (n = 12) squirrels collected in Scotland, UK, were analysed for the
      presence of this squirrel-associated virus. By using a newly developed real-time
      PCR targeting the adenoviral polymerase gene, viral DNA was detected in at least
      one of four tissue samples tested per animal in 64.0% of the red squirrels and
      41.7% of the grey squirrels. Exceptionally high viral genome loads were detected
      in the intestine and liver, but SqAdV-1 DNA was also present in lung and kidney
      samples of affected animals. Almost complete genome sequence determination of a
      red squirrel-derived SqAdV-1 strain from Scotland indicated a very high degree of
      identity to the first German strain. Sequence analysis of the hexon gene, which
      encodes one of the major antigens of the virion, revealed an identity of 100%
      between viruses found in red and grey squirrels from Scotland. In conclusion,
      SqAdV-1 appears to be widespread in the Scottish red and grey squirrel
      population, which highlights the necessity for continuous wildlife surveillance.
      The novel real-time PCR assay offers a highly sensitive and robust method for
      SqAdV-1 surveillance.

PMID- 30237073
TI  - In vivo mapping of brainstem nuclei functional connectivity disruption in
      Alzheimer's disease.
AB  - We assessed here functional connectivity changes in the locus coeruleus (LC) and
      ventral tegmental area (VTA) of patients with Alzheimer's disease (AD). We
      recruited 169 patients with either AD or amnestic mild cognitive impairment due
      to AD and 37 elderly controls who underwent cognitive and neuropsychiatric
      assessments and resting-state functional magnetic resonance imaging at 3T.
      Connectivity was assessed between LC and VTA and the rest of the brain. In
      amnestic mild cognitive impairment patients, VTA disconnection was predominant
      with parietal regions, while in AD patients, it involved the posterior nodes of
      the default-mode network. We also looked at the association between
      neuropsychiatric symptoms (assessed by the neuropsychiatric inventory) and VTA
      connectivity. Symptoms such as agitation, irritability, and disinhibition were
      associated with VTA connectivity with the parahippocampal gyrus and cerebellar
      vermis, while sleep and eating disorders were associated with VTA connectivity to
      the striatum and the insular cortex. This suggests a contribution of VTA
      degeneration to AD pathophysiology and to the occurrence of neuropsychiatric
      symptoms. We did not find evidence of LC disconnection, but this could be
      explained by the size of this nucleus, which makes it difficult to isolate. These
      results are consistent with animal findings and have potential implications for
      AD prognosis and therapies.

PMID- 30237075
TI  - Identification and characterization of differentially expressed Phaseolus
      vulgaris miRNAs and their targets during mungbean yellow mosaic India virus
      infection reveals new insight into Phaseolus-MYMIV interaction.
AB  - Phaseolus vulgaris is an economically important legume in tropical and
      subtropical regions of Asia, Africa, Latin-America and parts of USA and Europe.
      However, its production gets severely affected by mungbean yellow mosaic India
      virus (MYMIV). We aim to identify and characterize differentially expressed
      miRNAs during MYMIV-infection in P. vulgaris. A total of 422 miRNAs are
      identified of which 292 are expressed in both MYMIV-treated and mock-treated
      samples, 109 are expressed only in MYMIV-treated and 21 are expressed only in
      mock-treated samples. Selected up- and down-regulated miRNAs are validated by RT
      qPCR. 3367 target ORFs are identified for 270 miRNAs. Selected targets are
      validated by 5' RLM-RACE. Differentially expressed miRNAs regulate transcription
      factors and are involved in improving stress tolerance to MYMIV. These findings
      will provide an insight into the role of miRNAs during MYMIV infection in P.
      vulgaris in particular and during any biotic stress conditions in Leguminosae
      family in general.

PMID- 30237074
TI  - Age-related decline in cognitive flexibility in female chimpanzees.
AB  - Data on cognitive aging in chimpanzees are extremely sparse, yet can provide an
      invaluable phylogenetic perspective, especially because Alzheimer disease (AD)
      like neuropathology has recently been described in the oldest chimpanzee brains.
      This finding underscores the importance of data on cognitive aging in this fellow
      hominin, our closest biological relative. We tested 30 female chimpanzees, 12-56
      years old, on a computerized analog of the Wisconsin Card Sort test. This test
      assesses cognitive flexibility, which is severely impaired in normal aging and
      AD. Subjects selected stimuli according to color or shape; the rewarded dimension
      (i.e., color or shape) switched without warning and the chimpanzee had to adapt
      her responses accordingly. We found that increasing age was associated with an
      increased number of perseverative errors and an increased number of trials to
      reach criterion in each switching dimension. The number of aborted trials was
      similar across age groups. These data show that similar to humans, chimpanzees
      show a clear age-related decline in cognitive flexibility that is already
      observed at middle age.

PMID- 30237076
TI  - Identification and functional analysis of the doublesex gene in the sexual
      development of a hemimetabolous insect, the brown planthopper.
AB  - In the sex determination cascade, the genes dsx (doublesex) in insects, mab-3
      (male abnormal 3) in nematodes, and Dmrt1 (dsx/mab-3 related transcription factor
      1) in vertebrates act as the base molecular switches and play important roles.
      Moreover, these genes share the same conserved feature domain-DNA-binding
      oligomerization domain (OD1), and female-specific dsx also has a conserved
      oligomerization domain 2 (OD2). Although sex determination and the functions of
      dsx in several holometabolous insects have been well documented, sex
      determination and the function of dsx in hemimetabolous insects remain a mystery.
      In this study, four dsx homologs were unexpectedly found in the Nilaparvata
      lugens (brown planthopper, BPH, order Hemiptera), which also showed a different
      evolutionary status. We found that only one of the four homologs, Nldsx, which
      has three alternative splicing variants (female-specific NldsxF, male-specific
      NldsxM, non-sex-specific NldsxC), was required in the sexual development of N.
      lugens. Compared with that of holometabolous species, the dsx of N. lugens
      contains a less conserved OD1, while the OD2 domain of BPH was not identifiable
      because the common region is poorly conserved, and the female-specific region is
      short. RNAi-mediated knockdown of Nldsx in female BPH resulted in a larger body
      size with a normal abdomen and reproductive system, while no changes in fertility
      were noted. However, adult males with RNA interference knockdown of NldsxM in
      nymphs became pseudofemales, were infertile, had abnormal copulatory organs, and
      had impassable deferent ducts with hyperplastic walls; additionally, the
      pseudofemales could not produce the normal courtship signals. Our results suggest
      that dsx plays a critical role in male BPH somatic development and mating
      behavior. This is the first study to show that dsx is essential for sexual
      development in a hemipteran species.

PMID- 30237078
TI  - Antioxidant response of Arabidopsis thaliana seedlings to oxidative stress
      induced by carbon ion beams irradiation.
AB  - Due to the fact that carbon ion beams irradiation as an important type of
      ionizing radiation can potentially cause oxidative stress in plants, it is
      significant to evaluate the antioxidant response of plants to carbon ion beams
      radiation. Therefore, the objective of this study is to investigate the effects
      of carbon ion beams irradiation on oxidative stress induced by reactive oxygen
      species (ROS) and antioxidant response in Arabidopsis thaliana seedlings by
      irradiating the dry seeds at various doses of carbon ion beams (0, 50, 100, 150
      and 200 Gy) and measuring the plant growth parameters, ROS and malondialdehyde
      (MDA) levels, activities of antioxidant systems and antioxidant-related gene
      expression. The results showed that 50-Gy carbon ion beam irradiation exhibited
      stimulatory effects on germination index, root length and fresh weight in
      Arabidopsis seedlings, while high-dose irradiation (100-200 Gy) inhibited plant
      growth. Moreover, the production rate of superoxide anion radical, hydroxyl
      radical generation activity, hydrogen peroxide and MDA contents in Arabidopsis
      seedlings were obviously increased with the irradiation dose. Additionally, the
      antioxidant enzyme activities (superoxide dismutase, catalase and peroxidase) and
      non-enzymatic antioxidant contents (ascorbate and glutathione) in 50-Gy
      irradiated seedlings were apparently higher than control. Notably,
      transcriptional analysis displayed that 50-Gy carbon ion beams irradiation could
      enhance the expression of antioxidant-related genes in Arabidopsis seedlings.
      These results suggest that the improved activities of antioxidant systems induced
      by moderate ROS levels play important roles in growth promotion of Arabidopsis
      seedlings caused by low-dose carbon ion beams irradiation.

PMID- 30237077
TI  - The Manduca sexta serpinome: Analysis of serpin genes and proteins in the tobacco
      hornworm.
AB  - Members of the serpin superfamily of proteins occur in animals, plants, bacteria,
      archaea and some viruses. They adopt a variety of physiological functions,
      including regulation of immune system, modulation of apoptosis, hormone transport
      and acting as storage proteins. Most members of the serpin family are inhibitors
      of serine proteinases. In this study, we searched the genome of Manduca sexta and
      identified 32 serpin genes. We analyzed the structure of these genes and the
      sequences of their encoded proteins. Three M. sexta genes (serpin-1, serpin-15,
      and serpin-28) have mutually exclusive alternatively spliced exons encoding the
      carboxyl-terminal reactive center loop of the protein, which is the site of
      interaction with target proteases. We discovered that MsSerpin-1 has 14 splicing
      isoforms, including two undiscovered in previous studies. Twenty-eight of the 32
      M. sexta serpins include a putative secretion signal peptide and are predicted to
      be extracellular proteins. Phylogenetic analysis of serpins in M. sexta and
      Bombyx mori indicates that 17 are orthologous pairs, perhaps carrying out
      essential physiological functions. Analysis of the reactive center loop and hinge
      regions of the protein sequences indicates that 16 of the serpin genes encode
      proteins that may lack proteinase inhibitor activity. Our annotation and analysis
      of these serpin genes and their transcript profiles should lead to future
      advances in experimental study of their functions in insect biochemistry.

PMID- 30237079
TI  - A composite position independent monitor of reactor fuel irradiation using Pu,
      Cs, and Ba isotope ratios.
AB  - When post-irradiation materials from the nuclear fuel cycle are released to the
      environment, certain isotopes of actinides and fission products carry signatures
      of irradiation history that can potentially aid a nuclear forensic investigation
      into the material's provenance. In this study, combinations of Pu, Cs, and Ba
      isotope ratios that produce position (in the reactor core) independent monitors
      of irradiation history in spent light water reactor fuel are identified and
      explored. These position independent monitors (PIMs) are modeled for various
      irradiation scenarios using automated depletion codes as well as ordinary
      differential equation solutions to approximate nuclear physics models.
      Experimental validation was performed using irradiated low enriched uranium oxide
      fuel from a light water reactor, which was sampled at 8 axial positions from a
      single rod. Plutonium, barium and cesium were chemically separated and isotope
      ratio measurements of the separated solutions were made by quadrupole and multi
      collector inductively coupled mass spectrometry (Cs and Pu, respectively) and
      thermal ionization mass spectrometry (Ba). The effect of axial variations in
      neutron fluence and energy spectrum are evident in the measured isotope ratios.
      Two versions of a combined Pu and Cs based PIM are developed. A linear PIM model,
      which can be used to solve for irradiation time is found to work well for natural
      U fuel with <10% 240Pu and known or short cooling times. A non-linear PIM model,
      which cannot be solved explicitly for irradiation time without additional
      information, can nonetheless still group samples by irradiation history,
      including high burnup LEU fuel with unknown cooling time. 137Ba/138Ba is also
      observed to act as a position independent monitor; it is nearly single valued
      across the sampled fuel rod, indicating that samples sharing an irradiation
      history (same irradiation time and cooling time) in a reactor despite
      experiencing different neutron fluxes will have a common 137Ba/138Ba ratio.
      Modeling of this Ba PIM shows it increases monotonically with irradiation and
      cooling time, and a confirmatory first order analytical solution is also
      presented.

PMID- 30237080
TI  - Diagnosis and clinical behavior in patients with Lynch-like syndrome.
AB  - INTRODUCTION AND AIMS: Lynch-like syndrome is diagnosed when there is an
      expression deficit in DNA mismatch repair proteins but a normal genetic study.
      The behavior and management of that pathology are currently a subject of debate.
      We present herein the characteristics of patients with Lynch-like syndrome,
      together with a surveillance proposal. MATERIALS AND METHODS:
      Immunohistochemistry was carried out on families suspected of presenting with
      Lynch syndrome. Germline analysis was done if there was loss of mismatch repair
      protein expression and no BRAF mutation. RESULTS: Of the 148 patients that
      underwent immunohistochemistry testing, 23 presented with loss of mismatch repair
      protein expression. Seven of those patients were identified as having Lynch-like
      syndrome: 3had colon cancer, 2had endometrial tumor, and 2were healthy, with an
      affected relative. Mean patient age was 56.9 years and only one patient presented
      with another tumor associated with Lynch syndrome. CONCLUSIONS: Until there is a
      better understanding of the etiology of that heterogeneous entity, intermediate
      surveillance is an adequate strategy.

PMID- 30237081
TI  - Association of serum metabolites with impaired fasting glucose/diabetes and
      traditional risk factors for metabolic disease in Chinese adults.
AB  - BACKGROUND: Hyperglycemia has become a major health problem worldwide. We
      investigated the associations of serum metabolite levels with hyperglycemia
      (impaired fasting glucose/diabetes) and traditional risk factors for metabolic
      disease. METHODS: A total of 563 Chinese adults were categorized into
      hyperglycemia and control groups. Associations of serum metabolites, including
      branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), glutamine (Gln),
      glutamic acid (Glu), Gln/Glu ratio, 25-hydroxyvitamin D, and
      lysophosphatidylcholine (LPC), with hyperglycemia and traditional risk factors of
      metabolic disease were investigated using our targeted metabolomics method.
      RESULTS: Participants with impaired fasting glucose or diabetes exhibited
      markedly lower levels of Gln/Glu and unsaturated LPC and higher levels of Glu and
      BCAAs. Gln/Glu ratio, unsaturated LPC, and 25-hydroxyvitamin D were positively
      correlated with protective factors, while saturated LPC, BCAAs, AAAs, and Glu
      revealed close correlations with traditional risk factors. In the logistic
      regression, low Gln/Glu ratio and high BCAA level were independent risk factors
      for hyperglycemia; the odds ratios (95% confidence interval) of the highest
      quartile compared with the lowest quartile were 0.499 (0.274-0.910) and 2.588
      (1.313-5.102) (P < 0.05), respectively. CONCLUSIONS: Gln/Glu ratio, BCAAs, and
      LPC were significantly related to hyperglycemia development and risk factors for
      metabolic disease.

PMID- 30237082
TI  - Mesh: Prescribe like a drug.

PMID- 30237083
TI  - Xenotransplantation research and the 'International Journal of Surgery'.

PMID- 30237084
TI  - The evolutionary hypothesis of reaction specificity of mammalian ALOX15
      orthologs.

PMID- 30237085
TI  - Does spinal chloroprocaine pharmacokinetic profile actually translate into a
      clinical advantage in terms of clinical outcomes when compared to low-dose spinal
      bupivacaine? A systematic review and meta-analysis.
AB  - STUDY OBJECTIVE: Spinal anesthesia is well suited for day-care surgery, however a
      persisting motor block after surgery can delay discharge. Among the new drugs
      available, chloroprocaine has been associated with a short onset time, and motor
      block duration and a quicker discharge. However, it is not clear if those
      outcomes are clinically significantly superior compared to those associated with
      the use of low-dose hyperbaric bupivacaine. DESIGN: Aim of the study was to
      determine if spinal 2-chloroprocaine was superior to low-dose spinal bupivacaine
      regarding the following outcomes: onset time, block duration, time to ambulation
      and time to discharge. PATIENTS/INTERVENTIONS: We performed a systematic
      literature search of the last 30 years using PubMed Embase and the Cochrane
      Controlled Trials Register. We included only blinded, prospective trials
      comparing chloroprocaine with a low dose of bupivacaine for spinal anesthesia.
      Low dose bupivacaine was defined as a dose of 10 mg or less. Outcomes of interest
      were time to motor block regression (primary outcome), time to ambulation and
      time to discharge (secondary outcomes), as indirect indicators of a complete
      recovery after spinal anesthesia. MAIN RESULTS: Compared to a low dose
      bupivacaine, spinal 2-chloroprocaine was associated with significantly faster
      motor and sensory block regression (pMD = -57 min-140.3 min; P = 0.015 and <0.001
      respectively), a significantly shorter time to ambulation and an earlier
      discharge (pMD = -84.6 min; P < 0.001 and pMD = -88.6 min and <0.001
      respectively). Onset time did not differ between the two drugs (pMD = -1.1 min; P
      = 0.118). CONCLUSIONS: Spinal 2-chloroprocaine has a shorter motor block
      duration, a significantly quicker time to ambulation and time to discharge
      compared to low dose hyperbaric bupivacaine and may be advantageous when spinal
      anesthesia is performed for day case surgery.

PMID- 30237087
TI  - Corrigendum to 'Normative morphometric data for cerebral cortical areas over the
      lifetime of the adult human brain' [NeuroImage 156 (2017) 315-339].

PMID- 30237086
TI  - The combination of fecal calprotectin with ESR, CRP and albumin discriminates
      more accurately children with Crohn's disease.
AB  - PURPOSE: Increased fecal calprotectin is a sensitive marker of various types of
      intestinal inflammation. We investigated correlations between high fecal
      calprotectin concentration and serum inflammatory markers in children with
      different intestinal diseases with diarrhea with/without blood and/or abdominal
      pain, to test whether the combination of these markers can differentiate
      potential patients with inflammatory bowel disease. MATERIALS/METHODS: The study
      included 128 children with high fecal calprotectin concentration (>150ug/g) and
      symptoms suggesting bowel disorders, hospitalized in the years 2013- 2015. Twenty
      six (20%) patients were diagnosed with Crohn's disease, 55 (43%) with ulcerative
      colitis, 32 (25%) with intestinal infection and 15 (12%) with food protein
      induced proctocolitis. RESULTS: Significantly increased inflammatory markers were
      detected in children with inflammatory bowel disease, with a correlation between
      calprotectin and erythrocyte sedimentation rate - ESR (R = 0.53), mean
      corpuscular volume - MCV (R=-0.64), red blood cell distribution width (R = 0.56),
      albumin (R = -0.52), hemoglobin (R = -0.53) only in Crohn's disease patients. To
      discriminate Crohn's disease patients from patients with intestinal infection and
      patients with food protein induced proctocolitis, AUC analysis was performed. It
      revealed that considering ESR, CRP and albumin as additional markers to fecal
      calprotectin significantly improved diagnostic performance (AUC 0.917, p =
      0.038). CONCLUSIONS: In children with abdominal pain and/or diarrhea, increased
      ESR, CRP and decreased albumin combined with a high fecal calprotectin level
      yields additional diagnostic value in screening potential patients with Crohn's
      disease. As far as differentiation of ulcerative colitis is concerned, low
      additional diagnostic value was found when high fecal calprotectin was combined
      with albumin.

PMID- 30237088
TI  - Corrigendum to 'Normative data for subcortical regional volumes over the lifetime
      of the adult human brain' [NeuroImage 137 (2016) 9-20].

PMID- 30237089
TI  - OJIP-fluorescence parameters as rapid indicators of cotton (Gossypium hirsutum
      L.) seedling vigor under contrasting growth temperature regimes.
AB  - Vigorous seedling growth in cotton is desirable because it minimizes the negative
      impact of multiple early season stresses, and seedling vigor can be impacted by
      early season growth temperature or cultivar. OJIP fluorescence provides rapid
      information on a broad range of photosynthetic component processes and may be a
      useful surrogate for seeding vigor, but this possibility has not been evaluated
      previously in cotton. To this end, a controlled environment study was conducted
      with six cultivars selected based on seed characteristics that are widely
      indicative of vigor and under two growth temperature regimes (sub-optimal = 20/15
      degrees C day/night temperature; optimal = 30/20  degrees C) for the first two
      weeks after seed germination. Thereafter multiple whole-plant vigor assessments
      were conducted along with extensive OJIP-fluorescence characterization in
      cotyledons. Growth temperature was the primary factor influencing multiple plant
      responses. Specifically, all whole-plant indicators of seedling vigor were
      negatively impacted by sub-optimal temperature as were all photosynthetic
      performance indices and quantum efficiencies. By comparison, most photosynthetic
      structural indicators or reaction center-specific fluxes were either unaffected
      or positively impacted by low growth temperature, largely because PSII antenna
      size increased. The performance index, PIABS, and the quantum efficiency, phiEo,
      were the most sensitive to low growth temperature and exhibited the strongest
      relationships with whole-plant seedling vigor. Thus, OJIP parameters
      incorporating intersystem electron transport beyond PSII but not additional
      downstream processes may represent the most useful surrogates for whole-plant
      seedling vigor in cotton.

PMID- 30237091
TI  - Preoperative risk factors for early recurrence in patients with resectable
      pancreatic ductal adenocarcinoma after curative intent surgical resection.
AB  - BACKGROUND: Postoperative early recurrence (ER) in patients with pancreatic
      ductal adenocarcinoma (PDAC) is frequently encountered after curative intent
      surgery. Nonetheless, clinical significance and risk factors of ER after surgery
      for PDAC have not been extensively investigated. The aim of this study was to
      determine preoperative risk predictors for ER in patients with PDAC after upfront
      surgery. METHODS: Eighty-one consecutive patients with PDAC who underwent
      curative intent surgical resection at Kangbuk Samsung Hospital between January
      2004 and May 2015 were enrolled. ER was defined as tumor relapse within 6 months
      after surgery. RESULTS: ER occurred in 26 patients (32.1%), whereas 49 patients
      (60.5%) had late recurrence (>= 6 months after surgery), and 6 patients had no
      recurrence (7.4%). Univariate analysis showed that C-reactive protein (CRP) > 3.0
      mg/dL, modified Glasgow prognostic score (mGPS) = 2, decrease of total lymphocyte
      count by > 50% of baseline value in the preoperative period, prognostic
      nutritional index (PNI) < 45, neutrophil-to-lymphocyte ratio (NLR) >= 3, and
      preoperative maximum standardized uptake value (SUVmax) were significantly
      associated with ER. Multivariate logistic regression analysis revealed that CRP >
      3.0 mg/dL, decrease of total lymphocyte count by > 50% of baseline value, and
      preoperative SUVmax were significant and independent contributors of ER in
      patients with resectable PDAC who underwent curative intent surgery. CONCLUSIONS:
      Postoperative ER for resectable PDAC was frequent with poor prognosis after
      curative intent upfront surgery. It is reasonable to suggest that there is a
      subgroup of resectable PDAC patients at high-risk of ER and neoadjuvant therapy
      should be considered in these patients in a clinical trial setting.

PMID- 30237090
TI  - Comparative profiling of microRNAs and their effects on abiotic stress in wild
      type and dark green leaf color mutant plants of Anthurium andraeanum 'Sonate'.
AB  - MicroRNAs (miRNAs) are a class of non-coding small RNAs that play important roles
      in the regulation of gene expression. Although plant miRNAs have been extensively
      studied in model systems, less is known in other plants with limited genome
      sequence data, including Anthurium andraeanum. To identify miRNAs and their
      target genes in A. andraeanum and study their responses to abiotic stresses, we
      conducted deep-sequencing of two small RNA (sRNA) libraries prepared from young
      leaves of wild-type (WT) and dark green (dg) leaf color mutant plants of A.
      andraeanum 'Sonate'. A total of 53 novel miRNAs were identified, 32 of which have
      been annotated to 18 miRNA families. 10 putative miRNAs were found to be
      differentially expressed in WT and dg, among which two miRNAs were significantly
      up-regulated and eight down-regulated in dg relative to WT. One differentially
      expressed miRNA, Aa-miR408, was dramatically up-regulated in dg. qRT-PCR analysis
      and heterologous expression of Aa-miR408 in Arabidopsis under different stress
      treatments suggest that Aa-miR408 is involved in abiotic stress responses in A.
      andraeanum. Our results provide a foundation for further dissecting the roles of
      miRNAs and their targets in regulating abiotic stress tolerance in A. andraeanum.

PMID- 30237092
TI  - Single center observation of the role of pre-existing HLA-DP antibodies in
      humoral rejection following renal transplantation.
AB  - HLA antigens, including HLA-A, B, C, DR and DQ have long been known to have an
      effect on transplant outcome. Presence of antibodies to these antigens is
      detrimental to transplant outcome as it ends up to either acute or chronic
      humoral rejection depending on the titer of the antibodies to these antigens.
      However, the role of HLA-DP is not fully clear, predominantly due to lack of
      adequate publications and the fact that DP antigen and antibody detection became
      possible with the advent of new beads technology. As a results, allocation system
      has not yet included HA-DP antibodies in virtual crossmatching. This report
      presents two novel cases with strong HLA-DP antibodies which resulted in acute
      humoral rejection (AMR).

PMID- 30237093
TI  - Simultaneous quantification of Cyt c interactions with HSP27 and Bcl-xL using
      molecularly imprinted polymers (MIPs) coupled with liquid chromatography-tandem
      mass spectrometry (LC-MS/MS)-based targeted proteomics.
AB  - : Cytochrome c (Cyt c) plays an important role in cell apoptosis. However, it
      could be functionally compromised by interaction with anti-apoptosis proteins,
      known as protein-protein interactions (PPIs). Among the proteins potentially
      interacting with Cyt c, both HSP27 and Bcl-xL serve as pivotal anti-apoptosis
      proteins. Because multiple PPIs, especially those involve the same protein, could
      affect each other, their simultaneous and quantitative detection is highly
      needed. In this study, a combined approach of molecularly imprinted polymers
      (MIPs) and LC-MS/MS-based targeted proteomics was developed for simultaneous
      quantification of Cyt c-HSP27 and Cyt c-Bcl-xL interactions. Surrogate peptides
      of Cyt c, HSP27 and Bcl-xL were first selected and used for the corresponding
      proteins quantification in targeted proteomics analysis. For MIPs, epitope
      approach was employed and a short peptide of Cyt c was selected as template for
      protein complexes recognition and enrichment. The characteristics of the
      synthesized MIPs including adsorption capacity, kinetics and efficiency were then
      evaluated. After validation, this combined assay was applied to quantitative
      analysis of total Cyt c including Cyt c in mitochondria and cytosol, total HSP27,
      total Bcl-xL and Cyt c-HSP27 and Cyt c-Bcl-xL protein complexes in breast cells.
      The result was also compared with that using Co-IP/Western Blotting.
      SIGNIFICANCE: Protein-protein interactions (PPIs) are essential for many cellular
      processes and the changes of PPIs are often associated with cellular dysfunction.
      More importantly, each protein typically has more than one interaction partner
      and multiple PPIs, especially those involve the same protein, could affect each
      other. The selectivity of these interactions determines the activities of
      proteins and further the developmental potential of the cell. Thus, simultaneous
      and quantitative detection of multiple PPIs is highly needed in biological
      research and related disciplines. However, it is still challenging to even
      qualitatively or semi-quantitatively analyze multiple PPIs because of the
      limitations of current experimental techniques for interaction detection. In this
      study, molecularly imprinted polymers (MIPs) epitope approach was combined with
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted proteomics for
      the simultaneous and quantitative detection of Cyt c-HSP27 and Cyt c-Bcl-xL
      interactions in breast cancer. Given high sensitivity, high selectivity and wide
      dynamic range of LC-MS/MS, MIPs approach was employed here to separate and enrich
      protein complexes prior to targeted proteomics analysis.

PMID- 30237094
TI  - Effectiveness and acid/tooth brushing resistance of in-office desensitizing
      treatments-A hydraulic conductance study.
AB  - OBJECTIVE: To evaluate dentin permeability and tubule occlusion of in-office
      desensitizing treatments, and to analyze their resistance to erosive/abrasive
      challenges. DESIGN: Ninety-one 1mm-thick dentin discs were immersed in EDTA
      solution for 5 min. After analyzing the maximum dentin permeability, the
      specimens were randomly allocated into 7 experimental groups (n = 10): Control
      (no treatment); Er,Cr:YSGG laser; Nd:YAG laser; Gluma Desensitizer; Duraphat; Pro
      Argin toothpaste; Calcium Sodium Phosphosilicate (CSP) paste. The post-treatment
      permeability was assessed and then the specimens were subjected to a 5-day
      erosion-abrasion cycling protocol: 4x/day of immersion in citric acid solution (5
      min;0.3%), followed by exposure to clarified human saliva (60 min). After the
      first and last acid challenges, specimens were brushed for 15 s, with exposure to
      the toothpaste slurry for total time of 2 min. Dentin permeability was re
      measured (post-cycling). Percentage of dentin permeability for each experimental
      time was calculated in relation to the maximum permeability (%Lp). Data were
      analyzed with 2-way repeated measures ANOVA and Tukey tests (alpha = 0.05).
      Surface modifications were analyzed by scanning electron microscopy. RESULTS: In
      both experimental time CSP paste and Gluma Desensitizer did not differ from each
      other (p = 0.0874), and were the only groups that presented significantly lower
      %Lp than the Control (p = 0.026 and p = 0.022, respectively). After treatment,
      they were able to reduce dentin permeability in 82% and 72%, respectively. The
      %Lp post-cycling was higher than post-treatment value for all groups (p = 0.008).
      Dentin permeability increased 21% for CSP paste and 12% for Gluma, but they
      remained significant different from Control. Deposits on the surface were
      observed for CSP paste; and for Gluma, tubule diameters were shown to be smaller.
      CONCLUSIONS: CSP paste and Gluma Desensitizer were the only treatments able to
      decrease dentin permeability post-treatment and to sustain low permeability post
      cycling.

PMID- 30237095
TI  - Development and application of a method for discriminating the influence of radon
      progenies in air from aerial radiation monitoring data.
AB  - The influence of gamma-rays from natural nuclides (particularly the radon
      progenies, 214Pb and 214Bi) must be excluded from aerial radiation monitoring
      (ARM) data to accurately estimate the deposition of artificial radionuclides. A
      method for discriminating the influence of the radon progenies in air from the
      ARM data was developed. Two types of detectors with different crystal sizes were
      installed in a helicopter. The gamma-ray responses of these detectors were
      simulated using EGS5. The influence of the radon progenies in air was excluded
      using the relation between the count rates of six NaI (Tl) detectors and a LaBr3
      detector. The discrimination method was applied to the ARM data obtained from
      around the Sendai and Fukushima Dai-ichi Nuclear Power Stations. To verify the
      validity of the discrimination method, the dose rate estimated from the ARM data
      was compared with the dose rate measured using a NaI survey meter at a height of
      1 m above the ground. The application of the discrimination method improved the
      dose rate estimation, showing the validity of the discrimination method.

PMID- 30237096
TI  - Eye lens dose levels in interventional rooms using simple phantom simulation,
      dose management software and Monte Carlo method of uncertainty assessment.
AB  - This paper presents a fast method to estimate the annual eye lens dose levels for
      interventional practitioners applying the Monte Carlo method of uncertainty
      assessment. The estimation was performed by placing an anthropomorphic phantom in
      the typical working position, and applying the habitually employed protocol. No
      radiation protection devices were considered in the simulation. The results were
      compatible with the measurements performed during interventions by placing
      dosimeters in the vicinity of the eyes of two paediatric interventional
      cardiologists working with a fluoroscopic biplane system.

PMID- 30237097
TI  - Molecular epidemiology of coxsackievirus A6 circulating in Hong Kong reveals
      common neurological manifestations and emergence of novel recombinant groups.
AB  - BACKGROUND: Coxsackievirus A6 (CV-A6) represents the predominant enterovirus
      serotype in Hong Kong, but its epidemiology in our population was unknown.
      OBJECTIVES: To examine the clinical and molecular epidemiology of CV-A6 and
      detect emerging recombinant strains in Hong Kong. STUDY DESIGN: Nasopharyngeal
      aspirates (NPAs) from patients with febrile or respiratory illness were subject
      to RT-PCR for CV-A6 and sequencing of 5'-NCR and VP1. CV-A6-positive samples were
      further subject to 2C and 3D gene sequencing. Complete genome sequencing was
      performed on potential recombinant strains. RESULTS: Thirty-six (0.35%) NPAs were
      positive for CV-A6 by 5'-NCR RT-PCR and sequencing, 28 of which confirmed by
      partial VP1 gene sequencing. Among the 28 patients (mainly young children) with
      CV-A6 infection, hand-foot-and-mouth disease (HFMD) (43%), herpangina (18%) and
      tonsillitis (11%) were the most common diagnoses. Seven (25%) patients had
      neurological manifestations, including febrile seizures, encephalitis and
      meningitis. VP1 gene analysis showed that 24 CV-A6 strains circulating in Hong
      Kong belonged to genotype D5, while 4 strains belonged to D4. Further 2C and 3D
      gene analysis revealed eight potential recombinant strains. Genome sequencing of
      five selected strains confirmed four recombinant strains: HK459455/2013 belonging
      to recombination group RJ arisen from CV-A6/CV-A4, HK458288/2015 and
      HK446377/2015 representing novel group RL arisen from CV-A6/CV-A4, and
      HK462069/2015 representing novel group RM arisen from CV-A6/EV-A71. Recombination
      breakpoints located at 3D were identified in the latter three recombinant
      strains, with HK462069/2015 (from a child with encephalitis) having acquired 3D
      region from EV-A71. CONCLUSIONS: We identified novel recombinant CV-A6 strains in
      Hong Kong, with 3D being a common recombination site.

PMID- 30237098
TI  - Notes on recombination and reassortment in multipartite/segmented viruses.
AB  - Besides evolving through nucleotide substitution, viruses frequently also evolve
      by genetic recombination which can occur when related viral variants co-infect
      the same cells. Viruses with segmented or multipartite genomes can additionally
      evolve via the reassortment of genomic components. Various computational
      techniques are now available for identifying and characterizing recombination and
      reassortment. While these techniques have revealed both that all well studied
      segmented and multipartite virus species show some capacity for reassortment, and
      that recombination is common in many multipartite species, they have indicated
      that recombination is either rare or does not occur in species with segmented
      genomes. Reassortment and recombination can make it very difficult to study
      segmented/multipartite viruses using metagenomics-based approaches. Notable
      challenges include, both the accurate identification and assignment of genomic
      components to individual genomes, and the differentiation between natural 'real'
      recombination events and artifactual 'fake' recombination events arising from the
      inaccurate de novo assembly of genome component sequences determined using short
      read sequencing.

PMID- 30237100
TI  - Assessment of equine alpha-fetoprotein levels in mares and newborn foals in the
      periparturient period.
AB  - Alpha-fetoprotein (AFP) is best known in human obstetrics for its association
      with fetal anomalies recognized in the 1970s. Although this fetal protein had
      been shown to be present in the sera of many mammalian species, its possible
      diagnostic role in the detection of abnormalities was evaluated only later, when
      a research laboratory published variable levels of AFP in different groups of
      mares with pregnancy problems (twins, conception failure, placentitis, embryonic
      loss), and subsequently differences were demonstrated in its serum levels between
      aborted and healthy mares. In this study, peri- and intrapartal AFP levels were
      measured in maternal serum, amniotic fluid, neonatal blood, and umbilical blood
      samples. The mean levels of AFP were lower in umbilical blood and amniotic fluid
      samples than in foal and maternal blood. Older mares had lower AFP levels
      correlated with their age in years. The time remaining until foaling had a
      significant, non-linear effect on AFP levels: an elevation could be detected in
      the last two weeks of pregnancy, followed by a decline after foaling. Also, AFP
      levels were found to be elevated in the hot summer months. There was a
      significant individual variation in AFP levels in the population studied.

PMID- 30237102
TI  - Regulation of axonal EphA4 forward signaling is involved in the effect of EphA3
      on chicken retinal ganglion cell axon growth during retinotectal mapping.
AB  - The Eph and ephrins are involved in the genesis of topographic ordered
      connections at the visual system. Previously we demonstrated that tectal EphA3
      stimulates axon growth of nasal retinal ganglion cells (RGCs) toward the caudal
      tectum preventing them from branching in the rostral tectum. Now we investigated
      whether tectal EphA3 plays this role by modulating the axonal EphA4 forward
      signaling or throughout axonal ephrin-As reverse signaling. For this purpose we
      used cultures of nasal retinal explants and dissociated retinal neurons from
      chicken embryos. We treated them with clustered EphA3-Fc, Fc (control), PI-PLC
      (sheds ephrin-As) or KYL (inhibits ephrin-As-mediated EphA4 activation). We
      achieved in vitro and in vivo electroporations of chicken embryo retinas with
      wild type EphA4, Ki-EphA4 (kinase inactive dominant negative EphA4) or EGFP in
      pMES expression vector. We performed immunocytochemistry, immunoprecipitation and
      Western blot against Eph/ephrin-As system. Our results showed that: 1) shedding
      of ephrin-As and the inhibition of ephrin-A-mediated EphA4 activity increase axon
      length and decrease axonal interstitial filopodia density of nasal RGCs; and 2) a
      dominant negative form of EphA4 increases axon growth in vitro and induces nasal
      RGC axons to grow passing throughout their target area in the caudal tectum
      meanwhile overexpression of EphA4 produces the opposite effects. All together,
      these results demonstrate that ephrin-A-mediated EphA4 forward signaling
      decreases the level of axon growth and increases the density of axonal
      interstitial filopodia of nasal RGCs. Besides, our results showed that: 3) EphA3
      ectodomain increases axon growth and decreases the density of axonal interstitial
      filopodia and branching in vitro and in vivo and 4) EphA3 ectodomain diminishes
      the ephrin-A2/EphA4 colocalization, and the EphA4 and ephexin1 phosphorylation.
      All together, these results show that the EphA3 ectodomain produces the opposite
      effects than the EphA4 forward signaling, by decreasing this signaling pathway
      throughout competing with EphA4 for ephrin-As binding. Furthermore, it is
      proposed that tectal EphA3 participates in the establishment of retinotectal
      mapping throughout this mechanism and that EphAs can regulate axon growth and
      branching by modulating other EphA receptors forward signaling.

PMID- 30237099
TI  - Prognostic Impact of Presurgical CA19-9 Level in Pancreatic Adenocarcinoma: A
      Pooled Analysis.
AB  - BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall
      survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled
      analysis was to evaluate if presurgical CA19-9 level can also predict local
      control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred
      patients with PaC from eight institutions who underwent surgical resection +/-
      adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided
      based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull
      regression model to identify independent predictors of OS on 404 patients with
      complete information was fitted. RESULTS: Median follow-up was 17 months (range:
      2-225 months). Univariate analysis showed a better prognosis in pT1-2, pN0,
      diameter <30 mm, or grade 1 tumors and in patients undergoing R0 resection,
      distal pancreatectomy, or adjuvant chemotherapy and with lower CA19-9 levels.
      Five-year OS, LC, and DMFS were as follows: CA19-9 <5.0: 5.7%, 47.2%, 17.0%; CA19
      9 5.1-37.0: 37.9%, 63.3%, 46.0%; CA19-9 37.1-100.0: 27.1%, 59.4%, 39.0%; CA19-9
      100.1-353.0: 17.4%, 43.4%, 26.7%; CA19-9 >353.1: 10.9%, 50.2%, and 23.4%,
      respectively. At multivariate analysis, CA19-9 >100 and <353 level (P=.002), CA19
      9 >=353.1 (P<.001) level, G3 tumor (P=.002), and tumor diameter >30 mm (P<.001)
      correlated with worse OS. Patients treated with postoperative chemoradiation
      doses >50.0 Gy showed improved OS (P<.001). CONCLUSION: Presurgical CA19-9
      predicts both OS and pattern of failure. Therefore, CA19-9 should be included in
      predictive models in order to customize treatments based on prognostic factors.
      Moreover, future studies should stratify patients according to presurgical CA19-9
      level.

PMID- 30237101
TI  - Use of dimethylsulfoxide for semen cryopreservation in Indian red jungle fowl
      (Gallus gallus murghi).
AB  - Glycerol is a least toxic and most effective cryoprotectant for cryopreservation
      of poultry semen, but due to its contraceptive properties removal of glycerol is
      usually needed prior to artificial insemination. Dimethylsulfoxide (DMSO), a
      small amphiphilic molecule used as penetrating cryoprotectant for biological
      cells, has been recognized as an adequate alternative for cryopreservation of
      sperm from several species. This study was designed to evaluate the efficacy of
      different concentrations of DMSO as cryoprotectant for Indian red jungle fowl
      (Gallus gallus murghi) sperm. Semen was collected from Indian red jungle fowl
      cocks, pooled and divided into five aliquots. Different concentrations of DMSO
      (0%, 4%, 6%, 8% and 10%) were compared. Diluted semen was cooled from 37  degrees
      C to 4  degrees C (-0.275  degrees C min-1), 20% glycerol added to control and
      equilibrated for 10 min. After equilibration, semen was filled in 0.5 mL French
      straws, kept over liquid nitrogen vapors for 10 min and plunged into liquid
      nitrogen. Semen samples were thawed at 37  degrees C for 30 s. Cryo-survival of
      Indian red jungle fowl sperm was affected by cryopreservation stages and
      different concentrations of cryoprotectant used. Highest sperm motility (85.0 +/-
      2.9; 80.0 +/- 3.5; 71.3 +/- 4.3; 60.0 +/- 1.3), plasma membrane integrity (79.5
      +/- 3.8; 75.3 +/- 2.4; 72.8 +/- 3.3; 60.3 +/- 2.8), viability (80.8 +/- 4.6; 75.5
      +/- 2.9; 71.0 +/- 7.6; 58.8 +/- 1.3) and acrosomal integrity (76.3 +/- 2.4; 72.0
      +/- 6.0; 62.5 +/- 4.3; 55.0 +/- 3.2) were recorded in a diluent having 8% DMSO at
      post-dilution, cooling, equilibration and freeze-thawing. Highest fertility
      results were obtained after artificial insemination with 8% DMSO compared to 20%
      glycerol (73.0 +/- 4.4 vs 53.1 +/- 4.3, P < 0.05). It is concluded that 8% DMSO
      as a permeable cryoprotectant improves the post thaw semen quality and fertility
      in Indian red jungle fowl and can be used effectively to avoid the contraceptive
      effects of glycerol.

PMID- 30237103
TI  - Monovision: Consequences for depth perception from large disparities.
AB  - Recent studies have confirmed that monovision treatment degrades stereopsis but
      it is not clear if these effects are limited to fine disparity processing, or how
      they are affected by viewing distance or age. Given the link between stereopsis
      and postural stability, it is important that we have full understanding of the
      impact of monovision on binocular function. In this study we assessed the short
      term effects of optically induced monovision on a depth-discrimination task for
      young and older (presbyopic) adults. In separate sessions, the upper limits of
      stereopsis were assessed with participants' best optical correction and with
      monovision (-1D and +1D lenses in front of the dominant and non-dominant eyes
      respectively), at both near (62 cm) and far (300 cm) viewing distances.
      Monovision viewing resulted in significant reductions in the upper limit of
      stereopsis or more generally in discrimination performance at large disparities,
      in both age groups at a viewing distance of 300 cm. Dynamic photorefraction
      performed on a sample of four young observers revealed that they tended to
      accommodate to minimize blur in one eye at the expense of blur in the other.
      Older participants would have experienced roughly equivalent blur in the two
      eyes. Despite this difference, both groups displayed similar detrimental effects
      of monovision. In addition, we find that discrimination accuracy was worse with
      monovision at the 3 m viewing distance which involves fixation distances that are
      typical during walking. These data suggest that stability during locomotion may
      be compromised, a factor that is of concern for our older participants.

PMID- 30237104
TI  - Pronounced synergistic neuroprotective effect of GDNF and CNTF on axotomized
      retinal ganglion cells in the adult mouse.
AB  - Neuroprotection is among the potential treatment options for glaucoma and other
      retinal pathologies characterized by the loss of retinal ganglion cells (RGCs).
      Here, we examined the impact of a neural stem (NS) cell-based intravitreal co
      administration of two neuroprotective factors on the survival of axotomized RGCs.
      To this aim we used lentiviral vectors to establish clonal NS cell lines
      ectopically expressing either glial cell line-derived neurotrophic factor (GDNF)
      or ciliary neurotrophic factor (CNTF). The modified NS cell lines were
      intravitreally injected either separately or as a 1:1 mixture into adult mice one
      day after an optic nerve lesion, and the number of surviving RGCs was determined
      in retinal flat-mounts two, four and eight weeks after the lesion. For the
      transplantation experiments, we selected a GDNF- and a CNTF-expressing NS cell
      line that promoted the survival of axotomized RGCs with a similar efficacy. Eight
      weeks after the lesion, GDNF-treated retinas contained 3.8- and CNTF-treated
      retinas 3.7-fold more RGCs than control retinas. Of note, the number of surviving
      RGCs was markedly increased when both factors were administered simultaneously,
      with 14.3-fold more RGCs than in control retinas eight weeks after the lesion.
      GDNF and CNTF thus potently and synergistically rescued RGCs from axotomy-induced
      cell death, indicating that combinatorial neuroprotective approaches represent a
      promising strategy to effectively promote the survival of RGCs under pathological
      conditions.

PMID- 30237105
TI  - Learn to forget: Does post-exposure administration of d-cycloserine enhance fear
      extinction in agoraphobia?
AB  - The use of d-cycloserine (DCS) to augment exposure based therapy for anxiety
      disorders has shown mixed, although overall positive effects. Aim of the present
      study was to examine post-exposure administration of DCS in patients with
      agoraphobia with or without panic disorder. 73 patients with agoraphobia (with or
      without panic disorder) were treated with 12 sessions of cognitive behavioral
      therapy (CBT) including 3 exposures. Following successful exposure patients were
      given double blind either placebo or 50 mg of DCS. Primary outcome criterion was
      change in the Panic and Agoraphobia Scale (PAS) between CBT session t1, t4 (+~2
      months), t10 (+~3 months) und t11 (+~4 months). During the course of CBT the
      patients' symptomatology decreased significantly as measured by primary and
      secondary outcome criteria, however, without an additional benefit for DCS
      treated patients. Exploratory sub-group analyses for severely ill patients and
      patients with high anxiety and strong habituation during exposure showed that DCS
      administration was associated with increased improvement during the 1-month
      follow-up period (t10 - t11) with medium to large effect sizes (range in effect
      size eta2p from .06 to .25). Our study results are consistent with recent
      research on DCS, indicating a beneficial augmentative effect for sub-groups of
      anxiety patients. The lack of an overall DCS effect for the whole patient sample
      might be explained by a dual mechanism in fear conditioning and extinction with
      different cognitive processes being involved during exposure depending on the
      degree of anxiety experienced by the patient.

PMID- 30237106
TI  - The dilemma of benign multiple sclerosis: Can we predict the risk of losing the
      "benign status"? A 12-year follow-up study.
AB  - BACKGROUND: Definition of benign multiple sclerosis (BMS) remains controversial.
      Moreover, a sizeable proportion of classically defined BMS patients may be no
      longer benign (NLB) when re-assessed in the long-term. In a previous work, we
      found that after a five-year follow-up, a clinical score was able to identify
      patients at risk of losing their benign status. OBJECTIVES: In this 12-year
      reappraisal of the same cohort, we aimed at assessing the predictive value of the
      same score in the long-term. METHODS: After a mean follow-up of 12.6 + 0.4 years,
      patients still having an EDSS score <3.0 were classified as "still benign" (SB),
      whereas patients having an EDSS score >=3.5 were defined as NLB. The predictive
      value of the mentioned score was re-assessed using survival analysis. RESULTS: By
      the end of the follow-up, 20 (32.8%) were classified as NLB. Patients were
      grouped on the basis of the above mentioned score. Patients with score 2-3 were
      at higher risk of NLB status at the follow-up (HR = 3.5; 95%CI 1.5-8.6; p =
      0.005, accuracy = 70.5%). CONCLUSIONS: In patients with established BMS,
      prognostic prediction of longer-term disease course remains of critical value. In
      this study, a clinical score was able to predict disease evolution in the long
      term.

PMID- 30237107
TI  - Considerations for using Natalizumab treatment in patients with a history of
      choroidal melanoma.
AB  - Natalizumab is a monoclonal antibody licensed for the treatment of relapsing
      remitting multiple sclerosis (RRMS). It is known to increase the potential risk
      of developing progressive multifocal leukoencephalopathy (PML). There is current
      debate in the literature regarding its association with malignant melanoma.
      Herein, we report a case of a 55-year old lady with RRMS for whom natalizumab
      therapy was being considered by her neurologist. Her medical history included a
      choroidal melanoma which had undergone successful treatment. Additionally, in
      this case study we discuss the issues regarding malignant melanoma risk and
      recurrence with natalizumab treatment.

PMID- 30237108
TI  - Proton magnetic resonance spectroscopy differentiates tumefactive demyelinating
      lesions from gliomas.
AB  - BACKGROUND: It is often difficult to accurately differentiate tumefactive
      demyelinating lesions (TDLs) from gliomas using MRI. OBJECTIVE: To investigate
      the utility of proton magnetic resonance spectroscopy (MRS) in differentiating
      TDLs from gliomas. METHODS: Cohort 1 included 6 patients with TDLs and 5 with
      gliomas (3 high-grade), as assessed using a 1.5T MR unit. Cohort 2 included 6
      patients with TDLs and 17 patients with gliomas (8 high-grade), as assessed using
      a 3.0T MR unit. Single-voxel proton MRS was performed to compare the following
      metabolite area ratios: choline (Cho)/creatine (Cr), N-acetylaspartate (NAA)/Cr,
      and Cho/NAA in both cohorts. Correlations between the target-to-normal-tissue
      ratio (TNR) obtained using methionine-positron emission tomography (MET-PET) and
      each MRS metabolite ratio were examined in a subset of cohort 2 (4 patients with
      TDLs and 11 with gliomas). RESULTS: Mean Cho/NAA ratio was significantly higher
      in gliomas than in TDLs or MS in cohort 1 (p < 0.05). Mean Cho/NAA ratio was
      significantly higher in high-grade gliomas than in TDLs in both cohorts (ps <
      0.05). In the receiver operating characteristic analysis, high-grade glioma
      rather than TDL was indicated when the Cho/NAA ratio was >1.72 (the area under
      the curve was 0.958, and the maximum sensitivity and specificity were 100% and
      87%, respectively). A significant positive correlation was observed between
      Cho/NAA ratio and the MET-PET TNR (r2 = 0.35, p < 0.05). CONCLUSION: MRS
      effectively differentiates TDLs from high-grade gliomas. Therefore, the clinical
      use of MRS is likely to enhance patient outcomes.

PMID- 30237109
TI  - Cardiac safety evaluation in cancer clinical trials.
AB  - Identification and quantification of the cardiac adverse effects of new cancer
      therapeutics is important when comparing treatment arms in clinical trials. Heart
      failure and left ventricular dysfunction are some of the most common adverse
      cardiac effects of a range of cancer treatments, including anthracyclines,
      trastuzumab and other targeted agents. Using the example of trastuzumab-induced
      cardiac dysfunction, we evaluated phase III clinical trials performed over the
      past decade to establish the methods used to identify heart failure and
      impairment of left ventricular function. Both these adverse events are difficult
      to accurately quantify. A clinical diagnosis of heart failure is subjective, and
      measurement of left ventricular ejection fraction has high interobserver
      variability depending on the method used to measure it. We found there was
      heterogeneity in methods used to diagnose both these adverse events. In addition,
      the use of quality assurance techniques to reduce measurement variability was
      low. We discuss and propose methods to standardise and reduce variability of
      cardiac event assessment in cancer clinical trials. This will allow true
      comparison of cardiac events between arms and trials with the aim of ensuring
      cardiac safety data are accurate.

PMID- 30237110
TI  - Rates of electronic cigarette use among adults with a chronic mental illness.
AB  - INTRODUCTION: Electronic cigarette (e-cig) use has increased dramatically over
      the past decade, rates of e-cig use among those with a chronic mental illness has
      largely been unexplored. Exploring this relationship for adults with a mental
      illness is necessary when examining the health needs of this population. METHODS:
      Data from the 2016 National Health Interview Survey (NHIS) was used to explore
      associations between e-cig use and chronic mental illness. E-cig use was explored
      in two different contexts, having tried an e-cig at least once and current e-cig
      use. Chronic mental illness was categorized as depression, anxiety, emotional
      disorder, or ADD, bipolar, schizophrenia, other disorder. RESULTS: Rates of ever
      trying an e-cig and current e-cig use were higher among those with a chronic
      mental illness. Complex logistic regressions suggested having a chronic mental
      illness significantly increases the likelihood of both trying an e-cig and being
      an e-cig user. CONCLUSIONS: Increased likelihood of e-cig use in chronic mental
      illness supports previous findings. This may be due to perceptions that e-cigs
      are less harmful and they provide ways of socially connecting with others.
      IMPLICATIONS: Current knowledge surrounding e-cig use in this population is
      lacking. The 2016 NHIS allows for a nationally representative prediction of e-cig
      use in this population. This data is relevant in monitoring potential harm caused
      by e-cigs, in addition it may be helpful when assessing the value of e-cigs as a
      smoking cessation tool for those with a mental illness.

PMID- 30237111
TI  - Suicidal attempts among patients with substance use disorders who present with
      suicidal ideation.
AB  - BACKGROUND AND AIMS: Patients with addictions have a great risk of suicidal
      ideation and attempts. Suicidal behaviour is a continuum that begins with
      ideation and may continue with planning, attempts and suicide completion.
      Investigating the specific risk characteristics for suicidal attempts in patients
      with addiction problems who present with suicidal ideation is crucial for
      developing prevention strategies. The main aims of this study were to determine
      the prevalence rate of suicide attempts among patients with lifetime suicidal
      ideation receiving treatment for addiction, and to explore the differential
      characteristics for suicide ideators with and without suicide attempts. METHODS:
      A sample of 149 patients with suicidal ideation (110 male and 39 female) who
      sought treatment for addiction in a Spanish clinical centre was assessed.
      MEASUREMENTS: Information concerning socio-demographic characteristics, addiction
      severity, and psychopathological symptoms was obtained. RESULTS: In total, 39.6%
      of the patients had attempted suicide (95% Confidence Interval: 32.1%-47.6%).
      Although all patients with suicidal behaviours presented a high severity in their
      addiction, patients with both suicidal ideation and suicide attempts showed a
      more severe addiction profile and more maladjustment to everyday life than
      patients with only suicidal ideation. Specifically, three psychopathological
      variables were related to suicide attempts: worse psychiatric state, previous
      hospitalization for psychological problems, and history of delirium. CONCLUSIONS:
      According to the results, a systematic screening of suicidal risk in patients
      seeking treatment for addiction problems is recommended. Addiction treatment
      centres should develop treatment strategies to prevent suicidal ideators from
      attempting suicide, mainly in those cases with a worse lifetime psychiatric
      condition.

PMID- 30237112
TI  - Epidemiology of psychiatric disorders in children and adolescents; in Tehran,
      2017.
AB  - OBJECTIVE: This survey was conducted to investigate the prevalence of various
      psychiatric disorders among children and adolescents aged 6-18 years in urban
      areas of Tehran. METHODS: In the study, which was done with random sampling
      method, 2095 children and adolescents in the range seniors aged 6-18 years, have
      been studied and based on Persian version of K-SADS-PL, we reviewed the
      psychiatric disorders related to them. RESULTS: The overall prevalence of
      psychiatric disorders in children and adolescents was 28.2%. The most commonly
      diagnosed disorders were anxiety disorders (21.9%), followed by behavioral
      disorders (9.6%). CONCLUSION: According to the results, 28.2% of the children and
      adolescents in Tehran province had psychiatric disorders, that is with increasing
      rate, compared with similar studies. Therefore, as a public health policy, the
      necessary tools for identifying, preventing and treating psychiatric disorders in
      children and adolescents should be considered in Tehran.

PMID- 30237113
TI  - Thin liquid film between a floating oil droplet and a glass slide under DC
      electric field.
AB  - HYPOTHESIS: The shape of the liquid film (SLF) between a glass slide and an oil
      droplet immersed in an aqueous solution is influenced by the direct current (DC)
      electric field. The liquid film, consisting of the central film region and the
      meniscus film region, is formed between a floating oil droplet and a glass slide
      overhead. EXPERIMENTS: The SLF was experimentally studied in aqueous solutions of
      different ionic concentrations and pH values. After the DC electric fields were
      applied along the glass slide in horizontal direction, the diameter of central
      film and the thickness of meniscus film were measured by the interference method
      with an optical microscope. FINDINGS: The diameter of the central film decreases
      with the increase in the applied electric fields and declines at higher pH values
      while increases when the ionic concentration increases. The meniscus film becomes
      thicker with the increase in applied electric fields and is thicker in pH = 11
      solution and thinner in pH = 3 and 1 mM NaCl solution. This is the first study of
      dynamic thin liquid film under DC electric field, which may be attributed to the
      balance of dielectrophoretic (DEP) force, colloidal force and the deformable
      characteristic of the oil droplet.

PMID- 30237114
TI  - In situ growth of Ag-SnO2 quantum dots on silver phosphate for photocatalytic
      degradation of carbamazepine: Performance, mechanism and intermediates toxicity
      assessment.
AB  - The occurrence of carbamazepine (CBZ) in environments poses a potential risk to
      aquatic life and exhibits growth inhibition of human embryonic cells. In this
      work, for the first time a series of Ag-SnO2 quantum dots (QDs)/silver phosphate
      (AgSn/AgP) composites were synthesized and used as photocatalysts for CBZ
      degradation. The obtained AgSn/AgP composites showed superior photodegradation
      efficiency for CBZ removal. The degradation rate constant of 10AgSn/AgP (with 10
      wt% of Ag-SnO2 QDs) was almost 8.5, 5.7, 5.7, and 1.9 times as that of Ag-SnO2
      QDs, Ag3PO4, Ag/Ag3PO4, and SnO2 QDs/Ag3PO4, respectively. The improved
      photocatalytic activity could be primarily ascribed to the improved charge
      separation through a collaborative effect of Ag-SnO2 QDs and Ag3PO4, and in situ
      photoreduced metallic silver. Electron spin resonance (ESR) measurement and
      radical trapping experiments suggested that holes (h+), (superoxideradical) .O2-
      and (hydroxylradical) .OH corporately participated in the decomposition of CBZ.
      Moreover, a reasonable mechanism for photocatalytic degradation of CBZ over
      10AgSn/AgP composites was tentatively proposed. Additionally, eight degradation
      intermediates were determined by liquid chromatography-mass spectrometry (LC-MS).
      Toxicity evaluation using the Ecological Structure Activity Relationships
      (ECOSAR) program revealed that the toxicity of most photodegradation
      intermediates were much lower than that of the parent compound CBZ. This work not
      only provides a new technique for preparing Ag3PO4-based photocatalysts with high
      activity, but also demonstrates that 10AgSn/AgP could be a promising
      photocatalyst for treating water and wastewaters containing CBZ.

PMID- 30237115
TI  - The phase and charge of milk polar lipid membrane bilayers govern their selective
      interactions with proteins as demonstrated with casein micelles.
AB  - The biological membrane surrounding fat globules in milk (milk fat globule
      membrane; MFGM) is an interface involved in many biological functions and
      interactions with the surrounding proteins or lipolytic enzymes in the gastro
      intestinal tract during digestion. The MFGM exhibits lateral heterogeneities
      resulting from the different phase states and/or head-group charge of the polar
      lipids, which were both hypothesized to drive interaction with the casein
      micelles that is the major milk protein assembly. Atomic force microscopy (AFM)
      imaging was used to track the interactions of casein micelles with hydrated
      supported lipid bilayers of different composition, phase state and charge. Zeta
      potential and Langmuir isotherms of the different polar lipids offered additional
      information necessary to interpret AFM observations. We showed that the
      negatively-charged casein micelles did not interact with milk sphingomyelin in
      the gel or liquid-ordered phases but did interact with polar lipids in the liquid
      disordered phase (unsaturated polar lipids and milk sphingomyelin above its
      melting point). A wide intermolecular distance between polar lipids allowed
      protein adsorption on the membranes. However, the presence of the anionic polar
      lipids phosphatidylserine and phosphatidylinositol prevented any interaction with
      the casein micelles, probably due to electrostatic repulsion. These results open
      perspectives for the preparation of tailored emulsions covered by polar lipids
      able to modulate the interfacial interactions with proteins.

PMID- 30237116
TI  - Enhanced light absorption and charge recombination control in quantum dot
      sensitized solar cells using tin doped cadmium sulfide quantum dots.
AB  - The photovoltaic performance of quantum dot sensitized solar cells (QDSSCs) is
      limited due to charge recombination processes at the photoelectrode/electrolyte
      interfaces. We analyzed the effect of Sn4+ ion incorporation into CdS quantum
      dots (QDs) deposited onto TiO2 substrates in terms of enhancing light absorption
      and retarding electron-hole recombination at the TiO2/QDs/electrolyte interfaces.
      Sensitization involved depositing CdS QDs with different Sn4+ concentrations on
      the surface of TiO2 using a facile and cost-effective successive ionic layer
      adsorption and reaction (SILAR) method. Optimized photovoltaic performance of Sn
      CdS sensitized QDSSCs was explored using CuS counter electrodes (CEs) and a
      polysulfide electrolyte. Structural and optical studies of the photoanodes
      revealed that the gaps between CdS nanoparticles were partially filled by Sn4+
      ions, which enhanced the light absorption of the solar cell device.
      Electrochemical impedance spectroscopy (EIS) and open circuit voltage decay
      (OCVD) tests suggested that Sn4+ ions can remarkably retard electron-hole
      recombination at the interfaces, stimulate electron injection into semiconductor
      QD layers, and provide long-term electron lifetime to the cells. We found that
      solar cells based on CdS photoanodes doped with 10% Sn4+ ions exhibited a
      superior power conversion efficiency (PCE) of 3.22%, open circuit voltage (Voc)
      of 0.593 V, fill factor (FF) of 0.561, and short-circuit current density (Jsc) of
      9.68 mA cm-2 under an air mass coefficient (AM) 1.5 G full sun illumination.
      These values were much higher than those of QDSSCs based on bare CdS photoanodes
      (PCE = 2.16%, Voc = 0.552 V, FF = 0.471, and Jsc = 8.31 mA cm-2).

PMID- 30237117
TI  - Synaptic and intrinsic plasticity in the ventral tegmental area after chronic
      cocaine.
AB  - Cocaine exposure induces persistent changes in synaptic transmission and
      intrinsic properties of ventral tegmental area (VTA) dopamine neurons. Despite
      significant progress in understanding cocaine-induced plasticity, an effective
      treatment of cocaine addiction is lacking. Chronic cocaine potentiates excitatory
      and alters inhibitory transmission to dopamine neurons, induces dopamine neuron
      hyperexcitability, and reduces dopamine release in projection areas.
      Understanding how intrinsic and synaptic plasticity interact to control dopamine
      neuron firing and dopamine release could prove useful in the development of new
      therapeutics. In this review, we examine recent literature discussing cocaine
      induced plasticity in the VTA and highlight potential therapeutic interventions.

PMID- 30237118
TI  - Hand hygiene in hospitals: anatomy of a revolution.
AB  - Healthcare-associated infections (HAIs) affect hundreds of millions of
      individuals worldwide. Performing hand hygiene is widely accepted as a key
      strategy of infection prevention and control (IPC) to prevent HAIs, as healthcare
      workers' contaminated hands are the vehicle most often implicated in the cross
      transmission of pathogens in health care. Over the last 20 years, a paradigm
      shift has occurred in hand hygiene: the change from handwashing with soap and
      water to using alcohol-based hand rubs. In order to put this revolution into
      context and understand how such a change was able to be implemented across so
      many different cultures and geographic regions, it is useful to understand how
      the idea of hygiene in general, and hand hygiene specifically, developed. This
      paper aims to examine how ideas about hygiene and hand hygiene evolved from
      ancient to modern times, from a ubiquitous but local set of ideas to a global
      phenomenon. It reviews historical landmarks from the first known documented
      recipe for soap by the Babylon civilization to the discovery of chlorine, and
      significant contributions by pioneers such as Antoine Germain Labarraque,
      Alexander Gordon, Oliver Wendell Holmes, Ignaz Philip Semmelweis, Louis Pasteur
      and Joseph Lister. It recalls that handwashing with soap and water appeared in
      guidelines to prevent HAIs in the 1980s; describes why alcohol-based hand rub
      replaced this as the central tool for action within a multi-modal improvement
      strategy; and looks at how the World Health Organization and other committed
      stakeholders, governments and dedicated IPC staff are championing hand hygiene
      globally.

PMID- 30237120
TI  - Value of a hospital-wide point prevalence survey of carbapenemase-producing
      Enterobacterales - low-level prevalence confirmed.

PMID- 30237119
TI  - Differences in molecular epidemiology of Staphylococcus aureus and Escherichia
      coli in nursing home residents and people in unassisted living situations.
AB  - BACKGROUND: The usefulness of colonization pressure as a working model and proxy
      for infection transmission is limited due to the inability to grade or quantify
      the specific risk within environments that are subject to change. AIM: To
      elaborate on the colonization pressure model by comparing the molecular
      epidemiology of two bacteria, Staphylococcus aureus and Escherichia coli, among
      residents in a nursing home and people in unassisted living situations. METHODS:
      A cross-sectional study of 73 elderly residents from a village in south-central
      Sweden was conducted. Of these, 35 were residents of a nursing home, and 34 lived
      in an own place of residence in the same geographical area. Samples of two
      representative bacterial species were collected from multiple body sites and
      analysed for molecular diversity. FINDINGS: Combining all body sites, 47% of the
      participants were colonized with S. aureus and 93% with E. coli. The nursing home
      group, the group in unassisted living situations, and both units combined, held
      16, 17, and 29 different S. aureus spa types, respectively. The corresponding
      numbers of different E. coli serogenotypes were 34, 28, and 48. Diabetes mellitus
      was associated with more frequent colonization with S. aureus. CONCLUSION: The
      molecular diversity of bacteria found within different forms of accommodation was
      within the same range. Hospital quality hygiene might have contributed to the
      absence of homogenization of the molecular diversity within the nursing home
      group. Diabetes mellitus might have played a role in a patient selection
      characterized by advanced age.

PMID- 30237121
TI  - Stages of sarcopenia and the incidence of falls in older women: A prospective
      study.
AB  - The purpose of the present study was to assess the association between different
      stages of sarcopenia and the incidence of falls over 18 months in older community
      dwelling women. 246 women (68.1 +/- 6.2 years) underwent body composition using
      dual-energy x-ray absorptiometry, knee extensors isokinetic peak torque, and
      Timed Up-and-Go assessments. The stages of sarcopenia were classified according
      to the European Working Group on Sarcopenia in Older People. Volunteers were
      classified into four groups as follows: nonsarcopenia, presarcopenia, sarcopenia,
      and severe sarcopenia. Participants were tracked by phone calls for ascertainment
      of falls during a follow-up period of 18 months. Cox proportional regressions
      were conducted. A total of 195 women were followed over the 18-month period.
      Proportions of each sarcopenia stage were 6.7%, 13.8%, and 12.8% for
      presarcopenia, sarcopenia, and severe sarcopenia, respectively. The proportion of
      fallers progressively increased according to the severity of sarcopenia, with
      15.4%, 40.7%, and 72% for presarcopenia, sarcopenia, and severe sarcopenia,
      respectively (X2 = 30.637; p < 0.001). Severe sarcopenia was consistently
      associated with a higher risk of falls (hazard ratio: 3.843; 95% CI: 1.816
      8.131), even after adjustments for age, body mass index, physical activity level,
      regular use of four or more medications, reduced peripheral sensation, presence
      of two or more chronic diseases, and history of lower-limbs pain. It is concluded
      that severe sarcopenia is independently associated with higher incidence of falls
      in older women. These results provide support for the concept that sarcopenia
      staging has clinical implications and might be an useful supplement to other
      routine falls risk assessment tools.

PMID- 30237122
TI  - "It just happens". Care home residents' experiences and expectations of accessing
      GP care.
AB  - BACKGROUND: Care homes provide personal care and support for older people who can
      no longer be supported in the community. As part of a larger study of integrated
      working between the NHS and care homes we asked older people how they accessed
      health care services. Our aim was to understand how older people resident in care
      homes access health services using the Andersen model of health care access.
      METHODS: Case studies were conducted in six care homes with different socio
      economic characteristics, size and ownership in three study sites. Residents in
      all care homes with capacity to participate were eligible for the study.
      Interviews explored how residents accessed NHS professionals. The Andersen model
      of health seeking behaviour was our analytic framework. FINDINGS: Thirty-five
      participants were interviewed with an average of 4 different conditions.
      Expectations of their health and the effectiveness of services to mitigate their
      problems were low. Enabling factors were the use of intermediaries (usually
      staff, but also relatives) to seek access. Residents expected that care home
      staff would monitor changes in their health and seek appropriate help unprompted.
      CONCLUSIONS: Care home residents may normalise their health care needs and frame
      services as unable to remediate these which may combine to disincline older care
      home residents to seek care. Care access was enabled using intermediaries -either
      staff or relatives-and the expectation that staff would proactively seek care
      when they observed new/changed needs. Residents may over-estimate the health
      related knowledge of care home staff and their ability to initiate referrals to
      NHS professionals.

PMID- 30237123
TI  - Piperidinyl-embeded chalcones possessing anti PI3Kdelta inhibitory properties
      exhibit anti-atopic properties in preclinical models.
AB  - Phosphatidylinositide 3-kinases (PI3Ks) are widely expressed enzymes involved in
      membrane signalization pathways. Attempts to administer inhibitors with broad
      activity against different isoforms have failed due to toxicity. Conversely the
      PI3Kdelta isoform is much more selectively expressed, enabling therapeutic
      targeting of this isoform. Of particular interest PI3Kdelta is expressed in human
      basophils and its inhibition has been shown to reduce anti-IgE induced basophil
      degranulation, suggesting that PI3Kdelta inhibitors could be useful as anti
      allergy drugs. Herein, we report for the first time the activity of compounds
      derived from chalcone scaffolds as inhibitors of normal human basophil
      degranulation and identified the most active compound with anti-PI3Kdelta
      properties that was investigated in preclinical models. Compound 18, namely 1-[2
      hydroxy-4,6-dimethoxy-3-(N-methylpiperidin-4-yl)phenyl]-3-(2,4,6
      trimethoxyphenyl)-prop-2-en-1-one, was found to inhibit normal human basophil
      degranulation in a dose-dependent manner. In a murine model of ovalbumin-induced
      asthma, compound 18 was shown to reduce expiratory pressure while its impact on
      the inflammatory infiltrate in alveolar lavage and total lung was dependent on
      the route of administration. In a DNFB-induced model of atopic dermatitis
      compound 18 administered systemically proved to be as potent as topical
      betamethasone. These results support the anti-atopic and allergic properties of
      the title compound and warrant further clinical development.

PMID- 30237124
TI  - Synthesis and evaluation of novel arctigenin derivatives as potential anti
      Toxoplasma gondii agents.
AB  - Four new series of arctigenin derivatives were designed, synthesised, and
      evaluated for their anti-Toxoplasma gondii activity in vitro and in vivo. Among
      the synthesised compounds, 4-(3,4-dimethoxybenzyl)-3-(4-((1-(2-fluorobenzyl)-1H-
      1,2,3-triazol-4-yl)methoxy)-3-methoxybenzyl)dihydrofuran-2(3H)-one (D4) exhibited
      the most potent anti-T. gondii activity and low cytotoxicity (IC50 in T. gondii:
      17.1 MUM; IC50 in HeLa cells: >= 600.0 MUM; Selectivity: 35.09), demonstrating
      better results than the lead compound arctigenin (IC50 in T. gondii: 586.4 MUM;
      IC50 in HeLa cells: 572.7 MUM; Selectivity: 0.98) and the clinically applied
      positive-control drug spiramycin (IC50 in T. gondi: 262.2 MUM; IC50 in HeLa
      cells: 189.0 MUM; Selectivity: 0.72) in vitro. Furthermore, 2-(4-((4-(3,4
      dimethoxybenzyl)-2-oxotetrahydrofuran-3-yl)methyl)-2- methoxyphenoxy)N
      phenylacetamide (E5) had better inhibitory effects on T. gondii in vivo than
      spiramycin did. Compound D4 and E5 not only significantly reduced the number of
      tachyzoites in the peritoneal cavity of mice, but also resulted in their partial
      malformation (P < 0.05) in vivo. The determination of liver and spleen index and
      biochemical parameters, such as alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), glutathione (GSH) and malondialdehyde (MDA), were
      comprehensively evaluated for compound D4 and E5's anti-T. gondii activity and
      some damage to the liver. In addition, the results of a docking study of D4 into
      the T. gondii calcium-dependent protein kinase 1 (TgCDPK1) receptor protein
      binding site revealed that its mode of action was possibly as a TgCDPK1
      inhibitor. Overall, the results revealed that D4 and E5 are promising lead
      compounds for the further development and identification of arctigenin
      derivatives as anti-T. gondii agents.

PMID- 30237125
TI  - FIH permits NAA10 to catalyze the oxygen-dependent lysyl-acetylation of HIF
      1alpha.
AB  - The N-terminal acetyltransferase A (NatA) complex, which is composed of NAA10 and
      NAA15, catalyzes N-terminal acetylation of many proteins in a co-translational
      manner. Structurally, the catalytic subunit NAA10 was believed to have no
      activity toward an internal lysine residue because the gate of its catalytic
      pocket is too narrow. However, several studies have demonstrated that the
      monomeric NAA10 can acetylate the internal lysine residues of several substrates
      including hypoxia-inducible factor 1alpha (HIF-1alpha). How NAA10 acetylates
      lysine residues has been an unsolved question. We here found that human FIH
      (factor inhibiting HIF) hydroxylates human NAA10 at W38 oxygen-dependently and
      this permits NAA10 to express the lysyl-acetyltransferase activity. The
      hydroxylated W38 forms a new hydrogen-bond with A67 and widens the gate at the
      catalytic pocket, which allows the entrance of a lysine residue to the site.
      Since the FIH-dependent hydroxylation of NAA10 occurs oxygen-dependently, NAA10
      acetylates HIF-1alpha under normoxia but does not under hypoxia. Consequently,
      the acetylation promotes the pVHL binding to HIF-1alpha, and in turn HIF-1alpha
      is destructed via the ubiquitin-proteasome system. This study provides a novel
      oxygen-sensing process that determines the substrate specificity of NAA10
      depending on an ambient oxygen tension.

PMID- 30237128
TI  - Biochemical characterization of chitinase A from Bacillus licheniformis DSM8785
      expressed in Pichia pastoris KM71H.
AB  - Chitin is an abundant biopolymer found mainly in the exoskeleton of crustaceans
      and insects. The degradation of chitin using chitinases is one way to address the
      accumulation of chitin waste streams in the environment, and research has
      therefore focused on the identification, improvement and expression of suitable
      enzymes. Here we describe the production, purification and characterization of
      Bacillus licheniformis chitinase A in the Pichia pastoris expression system.
      Optimal enzyme activity occurred at pH 4.0-5.0 and within the temperature range
      50-60  degrees C. With colloidal chitin as the substrate, the Km (2.307 mM) and
      Vmax (0.024 mM min-1) of the enzyme were determined using a 3,5-dinitrosalicylic
      acid assay. The degradation products of colloidal chitin and hexa-N
      acetylchitohexaose were compared by thin-layer chromatography. The activity of
      the glycosylated enzyme produced in P. pastoris was compared with the in vitro
      deglycosylated and aglycosylated version produced in Escherichia coli. We showed
      that the glycosylated chitinase was more active than the deglycosylated and
      aglycosylated variants.

PMID- 30237129
TI  - Application of infrared spectrum for rapid classification of dominant petroleum
      hydrocarbon fractions for contaminated site assessment.
AB  - In this study, the infrared spectrum (4000-400 cm-1) was applied to identify and
      classify the different alkanes based on carbon chain length (Cn). It was found
      there were two bands coherent to the doublet at location 2954 and 2872 cm-1,
      respectively can be applied to identify the fraction of carbon chains. From C20
      to C37, by the increase of the Cn, the intensities of the two bands were reduced
      as demonstrated. There were another two doublets existed at the region from 1480
      to 1450 cm-1 and the region at 750 and 730 cm-1. It was observed the intensity of
      one coherent band at each of these regions was increased following the increase
      on the Cn. The bands center at 1462 and 730 cm-1 were increased from C20 to C37.
      The intensity ratio of the coherent bands can be applied to identify the Cn.
      Successfully identify four different petroleum products with different fractions
      of carbon chains in soil samples, is evidence the theory can be applied to
      investigate the fraction of carbon chains in soil. Coupling with handheld FTIR,
      it is possible to rapidly estimate the dominant fraction of Cn in soil in field.

PMID- 30237127
TI  - Chlorination and oxidation of human plasma fibronectin by myeloperoxidase-derived
      oxidants, and its consequences for smooth muscle cell function.
AB  - Fibronectin (FN) occurs as both a soluble form, in plasma and at sites of tissue
      injury, and a cellular form in tissue extracellular matrices (ECM). FN is
      critical to wound repair, ECM structure and assembly, cell adhesion and
      proliferation. FN is reported to play a critical role in the development,
      progression and stability of cardiovascular atherosclerotic lesions, with high FN
      levels associated with a thick fibrotic cap, stable disease and a low risk of
      rupture. Evidence has been presented for FN modification by inflammatory
      oxidants, and particularly myeloperoxidase (MPO)-derived species including
      hypochlorous acid (HOCl). The targets and consequences of FN modification are
      poorly understood. Here we show, using a newly-developed MS protocol, that HOCl
      and an enzymatic MPO system, generate site-specific dose-dependent Tyr
      chlorination and dichlorination (up to 16 of 100 residues modified), and
      oxidation of Trp (7 of 39 residues), Met (3 of 26) and His (1 of 55) within
      selected FN domains, and particularly the heparin- and cell-binding regions.
      These alterations increase FN binding to heparin-containing columns. Studies
      using primary human coronary artery smooth muscle cells (HCASMC) show that
      exposure to HOCl-modified FN, results in decreased adherence, increased
      proliferation and altered expression of genes involved in ECM synthesis and
      remodelling. These findings indicate that the presence of modified fibronectin
      may play a major role in the formation, development and stabilisation of fibrous
      caps in atherosclerotic lesions and may play a key role in the switching of
      quiescent contractile smooth muscle cells to a migratory, synthetic and
      proliferative phenotype.

PMID- 30237130
TI  - A variable temperature infrared spectroscopy study of CaA zeolite dehydration and
      carbonate formation.
AB  - Variable temperature diffuse reflection infrared spectroscopy is used to monitor
      the dehydration of calcium enriched Linde type A zeolite (CaA). Infrared spectrum
      changes indicate that the energy imparted to the zeolite by heating causes water
      desorption and also facilitates reactions between water and zeolite framework,
      yielding SiOHAl acid sites. Water also reacts with ambient carbon dioxide
      producing carbonic acid, which readily dissociates to form carbonate. Three types
      of carbonate species are reported. The most thermally stable carbonate is
      coordinated to Ca2+ as a monodentate ligand. A second carbonate-containing
      species may be simultaneously interacting with Ca2+ and the zeolite framework.
      The third type of carbonate is characterized by infrared absorption consistent
      with a highly symmetric configuration, suggesting weak interactions with the
      local environment. Temperature-dependent infrared spectrum variations suggest
      that protons from carbonic acid dissociations react with framework and Ca(OH)+
      moieties, altering internal CaA pore structure configurations.

PMID- 30237126
TI  - Curcumol induces RIPK1/RIPK3 complex-dependent necroptosis via JNK1/2-ROS
      signaling in hepatic stellate cells.
AB  - It is generally recognized that hepatic fibrogenesis is an end result of
      increased extracellular matrix (ECM) production from the activation and
      proliferation of hepatic stellate cells (HSCs). An in-depth understanding of the
      mechanisms of HSC necroptosis might provide a new therapeutic strategy for
      prevention and treatment of hepatic fibrosis. In this study, we attempted to
      investigate the effect of curcumol on necroptosis in HSCs, and further to explore
      the molecular mechanisms. We found that curcumol ameliorated the carbon
      tetrachloride (CCl4)-induced mice liver fibrosis and suppressed HSC proliferation
      and activation, which was associated with regulating HSC necroptosis through
      increasing the phosphorylation of receptor-interacting protein kinase 1 (RIPK1),
      receptor-interacting protein kinase 3 (RIPK3). Moreover, curcumol promoted the
      migration of RIPK1 and RIPK3 into necrosome in HSCs. RIPK3 depletion impaired the
      anti-fibrotic effect of curcumol. Importantly, we showed that curcumol-induced
      RIPK3 up-regulation significantly increased mitochondrial reactive oxygen species
      (ROS) production and mitochondrial depolarization. ROS scavenger, N-acetyl-L
      cysteine (NAC) impaired RIPK3-mediated necroptosis. In addition, our study also
      identified that the activation of c-Jun N-terminal kinase1/2 (JNK1/2) was
      regulated by RIPK3, which mediated curcumol-induced ROS production. Down
      regulation of RIPK3 expression, using siRIPK3, markedly abrogated JNK1/2
      expression. The use of specific JNK1/2 inhibitor (SP600125) resulted in the
      suppression of curcumol-induced ROS production and mitochondrial depolarization,
      which in turn, contributed to the inhibition of curcumol-triggered necroptosis.
      In summary, our study results reveal the molecular mechanism of curcumol-induced
      HSC necroptosis, and suggest a potential clinical use of curcumol-targeted
      RIPK1/RIPK3 complex-dependent necroptosis via JNK1/2-ROS signaling for the
      treatment of hepatic fibrosis.

PMID- 30237131
TI  - Relationships between muscle electrical activity and the control of inter
      vertebral motion during a forward bending task.
AB  - Muscle strengthening exercises are commonly used in primary care for the
      treatment of chronic, non-specific low back pain (CNSLBP) as it has been
      theorised that increased muscle activity contributes to the stabilisation of
      inter-vertebral motion segments during bending and other spinal movements,
      however this has never been demonstrated in vivo. This study used contemporaneous
      quantitative fluoroscopy (QF) and surface electromyography (sEMG) to investigate
      relationships between continuous inter-vertebral motion variables and muscle
      electrical activity in the lumbar multifidus (LMU), lumbar and thoracic erector
      spinae (LES and TES) during standardised lumbar flexion and return in 18 healthy
      male human subjects. Our results demonstrated that the variability in the sharing
      of angular motion (i.e. Motion Share Variability MSV) and motion segment laxity
      during a bending task were significantly (p < 0.05) negatively correlated
      (Spearman) with muscle electrical activity throughout the participant bend for
      both locally and globally acting muscle groups. MSV was also strongly correlated
      with L2-3 laxity. The former suggests a damping mechanism reducing irregular
      displacements (i.e. less variability in the sharing of segmental motion) during
      bending and an action of spinal stabilisation by muscles at segmental levels, and
      the latter a synergy between laxity at L2-3 and MSV. While this has previously
      been theorised, it has never been shown in vivo at the inter-vertebral level.
      These assessments may be considered for use in validation studies of exercise
      programs for CNSLBP, however further replication is required.

PMID- 30237132
TI  - Representing fine-wire EMG with surface EMG in three thigh muscles during high
      knee flexion movements.
AB  - Activation waveforms of vastus intermedius, adductor magnus, and semimembranosus
      have not been reported for high knee flexion activities such as kneeling or
      squatting, likely due to the invasive procedures required for their measurement.
      Their relatively large physiological cross sectional areas would suggest their
      contributions to knee joint loading could be considerable. Therefore, the purpose
      of this study was to quantify the activities of these muscles using fine-wire EMG
      and to assess easy to measure surface sites (vastus lateralis, rectus femoris,
      vastus medialis, semitendinosus, and biceps femoris) for their potential as proxy
      measures using <10 %MVC RMS and >0.85 R2 as criteria for successful
      representation of deep muscle activity by that measured at a surface site.
      Overall, no surface and fine-wire site pair met both criteria for these
      movements. When fine-wire measurement of muscle activity is infeasible or
      impractical, the waveforms presented in supplementary material could be used as a
      guide for the activity of these deep muscles. Although select muscles for some
      participants satisfied our criteria, inter-participant variability was
      considerable. Therefore, future muscle models may benefit from fine-wire
      measurement of these muscles, but researchers should be cautious of electrode
      site specificity.

PMID- 30237133
TI  - Relationship between hand grip strength and endurance and postural stability in
      active and sedentary older women.
AB  - Physical activity, muscle strength and the ability to maintain postural stability
      (PS) are important for well-being in old age. Therefore, the first aim of this
      study was to assess the contractile abilities of the hand muscles (CAHM) in
      physically active (PA) and sedentary (SED) older women. The second aim was to
      examine the relationship between CAHM and PS indicators in older women. The
      sample of 75 women (aged 65-86 years), was divided into PA and SED group.
      Differences in CAHM, namely rate of force development and muscular endurance,
      were confirmed in favor of PA group, whereas, no differences were found between
      PA and SED group regarding maximum force. Moreover, CAHM were moderately
      associated with PS indicators. Obtained results could open space for designing
      routine tests that might serve as a potential prescreening analysis, which could
      indicate early risk factors for falls along with other age related health issues.

PMID- 30237135
TI  - A low fetal cerebroplacental ratio confers a greater risk of intrapartum fetal
      compromise and adverse neonatal outcomes in low risk multiparous women at term.
AB  - BACKGROUND: A low fetal cerebroplacental ratio (CPR) and nulliparity have
      independently been shown to be associated with adverse obstetric and perinatal
      outcomes. OBJECTIVES: To assess the effect of parity on the CPR and investigate
      the utility of a CPR threshold of <10th centile for predicting adverse outcomes.
      We hypothesised that nulliparous women would have a lower CPR than multiparous
      women, impacting the diagnostic performance of the <10th centile threshold. This
      is an important consideration for interpretation of a low CPR in clinical
      practice. STUDY DESIGN: This was a retrospective cohort study of low risk,
      singleton pregnancies delivering at term in Australia's largest maternity
      hospital. The primary outcome was emergency caesarean section for intrapartum
      fetal compromise (EmCS IFC). Data was dichotomised according to parity and
      further by CPR <10th centile. Multiple logistic regression was performed.
      RESULTS: 4737 women were included for analysis, 2333 were nulliparous and 2404
      were multiparous. Overall the z-score (mean [SD])(CPR standardised for gestation)
      was lower in nulliparous compared to multiparous women (-0.16 [-1.73 - 1.42] vs
      0.04 [-1.63 - 1.69], p < 0.001). Multiparous women had a non-significantly lower
      mean z-score for those who delivered by EmCS IFC than nulliparous women (-0.52 [
      2.23 - 2.02] vs -0.45 [-2.22 - 1.1]). Nulliparous women had greater odds of
      having a CPR <10th centile compared to the multiparous cohort (OR 1.24, 95% CI
      1.02-1.5 vs. OR 0.81, 95% CI 0.7-0.98, p < 0.001). A CPR thresholdd <10th centile
      in nulliparous women was associated with increased odds of intrapartum fetal
      compromise (IFC), EmCS IFC (aOR 1.72, 95CI 1.2-2.6, p < 0.05) and birthweight
      <10th centile. A low CPR in multiparous women was associated with increased odds
      of all adverse perinatal outcomes measured: IFC, meconium stained liquor, EmCS
      IFC (aOR 4.99, 95%CI 2.5-9.9, p < 0.001), birthweight <10th centile, acidosis,
      neonatal intensive care admission and severe composite neonatal outcome. These
      aORs were associated with specificities of >90% and false positive rates of <10%
      for all outcomes in multiparous women. CONCLUSIONS: A CPR <10th centile in
      multiparous women confers greater odds of adverse perinatal outcomes and as such
      of the influence of parity should be taken into account when decisions regarding
      clinical management are made because of a low CPR.

PMID- 30237134
TI  - Three Lycopodium alkaloids from Thai club mosses.
AB  - Phytochemical constituents in alkaloid extracts from three Thai club mosses
      Huperzia squarrosa, Huperzia phlegmaria and Phlegmariurus nummularifolius were
      investigated. Squarrosinoxide was an undescribed Lycopodium alkaloid from H.
      squarrosa possessing an unprecedented 6/5/7 tricyclic spiro system.
      Acetyllycophlegmarianol was an undescribed N-oxide lycopodine-type alkaloid
      isolated from H. phlegmaria. 4-Epilycopodine, an undescribed epimer of
      lycopodine, was first isolated from P. nummularifolius. The structural
      assignments were established through comprehensive spectroscopic techniques and
      chemical correlations. All compounds were assayed for their anti
      acetylcholinesterase activity in vitro.

PMID- 30237136
TI  - The outcome of the multifetal pregnancy reduction procedures in a single centre:
      A report of 202 completed cases.
AB  - OBJECTIVE: To review the results of fetal reduction procedures in our
      institution, evaluate its effects on the pregnancy outcome in terms of
      miscarriage, preterm delivery, taking home healthy babies and discuss the factors
      that may have contributed to the outcome. STUDY DESIGN: This is a retrospective
      study performed at the Fetal Medicine Unit of the Sisli Memorial Hospital in
      Istanbul after ART therapies in our unit from 2000 to 2011. RESULTS: The sample
      comprised 151 triplets, 35 quadruplets, 11 quintuplets, 3 twins, 1 sextuplet and
      1 septuplet. The average maternal age was 30 +/- 4.4 and the average week of
      interventions was 11.7 +/- 1.3 weeks. In 40 cases two or more needle insertions
      were necessary. The two-week post-procedure loss rate, defined as 'the procedure
      related loss rate', was 0.7%; however, for the whole sample, the losses were 6.9%
      when they occured before 24 completed weeks and was defined as 'the total loss
      rate'. 184 of the remaining 188 cases had at least one baby to take home (91.1%
      of 202 patients). The average birth week for those healthy babies discharged home
      was 35.5 +/- 2.4. The rate of early preterm birth before gestational weeks of 32
      was 9%. The mean birthweight of this "take-home" group was 2302 +/- 525 g.
      CONCLUSION: Fetal reduction in multifetal pregnancy is associated with low
      miscarriage rate and preterm delivery rates. Fetal reduction in multifetal
      pregnancy should be considered for better pregnancy outcomes and the results of
      this study can be used in prenatal counseling.

PMID- 30237137
TI  - Mode of delivery following an OASIS and caesarean section rates.
AB  - OBJECTIVES: While the rate of obstetric anal sphincter injury (OASIS) is
      increasing, there is a lack of evidence on how best to advise women on mode of
      delivery (MOD) afterwards. The objectives of this study were to assess the
      clinical value of bowel symptoms, endoanal ultrasound and anorectal manometry in
      the management of pregnancies after an OASIS and evaluate the performance of
      different algorithms. STUDY DESIGN: This was a retrospective analysis of
      prospectively collected data in a university hospital perineal clinic. Women with
      OASIS undergoing endoanal ultrasound scan (EAUS) and anorectal manometry (AM)
      were included in this study (all women with an OASIS, except the asymptomatic 3a
      tears). A number of published algorithms were theoretically applied in this
      cohort to define recommended MOD after an OASIS. RESULTS: Out of the 233 women
      included in the study, 51 (21.9%) were symptomatic, 141 (60.5%) had persistent
      sphincter defects on EAUS and 124 (53.2%) had abnormal AM. One asymptomatic and
      five symptomatic women were found to have isolated internal anal sphincter (IAS)
      defects without external anal sphincter (EAS) defects. There were no women with
      low resting pressure and normal incremental squeeze pressure. The application of
      the algorithm requiring only one abnormal investigation to be recommended
      caesarean would have led to an 81.5% caesarean rate. If women with symptoms of
      anal incontinence or abnormal investigations would be advised for caesarean the
      rate would be 85.0%. Using the local protocol where symptomatic women only needed
      one of the two investigations to be abnormal but asymptomatic women were required
      to have both investigations being abnormal, 94 were considered for caesarean
      (40.3%). CONCLUSION: There is a wide range in the number of patients recommended
      to have caesarean section after an OASIS, depending on the used criteria and
      management algorithms. There is minimal additional information gained from
      identifying internal anal sphincter defects and measuring low resting pressures
      at manometry.

PMID- 30237138
TI  - Vaginal progesterone for the prevention of preterm birth and the risk of
      gestational diabetes.
AB  - INTRODUCTION: We aimed to determine whether daily vaginal progesterone use for
      the prevention of preterm birth has an effect on the incidence of abnormal
      glucose challenge test or gestational diabetes. STUDY DESIGN: A retrospective
      study in a large referral center. Women with cervical length <= 25 mm were given
      200 mg vaginal micronized progesterone capsules daily at bed time until 36 weeks'
      gestation or delivery. Each progesterone-treated woman was matched randomly with
      three untreated controls. The main outcome measures were; mean plasma glucose
      level following the glucose challenge test and the rate of abnormal 1-hour
      glucose challenge test. Secondary outcome was the rate of gestational diabetes.
      RESULTS: We identified 108 progesterone-treated women that were matched by age
      and BMI to 324 controls during the same time period. The mean plasma glucose
      level following the glucose challenge test was similar in both groups (115.3 +/-
      33.8 mg/dL versus 109.2 +/- 26.6 mg/dL). Despite a higher rate of an abnormal
      glucose challenge test in the progesterone-treated group compared to the control
      group (21.1% vs. 13.9%), it did not reach statistical significance. Similarly, we
      could not detect any difference in the rate of gestational diabetes in either the
      study or the control group (2.8% versus 2.5%). CONCLUSION: Daily vaginal
      progesterone was not associated with higher rates of abnormal glucose challenge
      test or gestational diabetes. We are in a view that no earlier screening or
      diagnostic testing for gestational diabetes is required except the standard
      recommended schedule unless additional risk factors are present.

PMID- 30237139
TI  - Expansion of the metazoan virosphere: progress, pitfalls, and prospects.
AB  - Metagenomic sequencing has led to a recent and rapid expansion of the animal
      virome. It has uncovered a multitude of new virus lineages from under-sampled
      host groups, including many that break up long branches in the virus tree, and
      many that display unexpected genome sizes and structures. Although there are
      challenges to inferring the existence of a virus from a 'virus-like sequence', in
      the absence of an isolate the analysis of nucleic acid (including small RNAs) and
      sequence data can provide considerable confidence. As a consequence, this period
      of molecular natural history is helping to reshape our views of deep virus
      evolution.

PMID- 30237140
TI  - Generation of induced pluripotent stem cell line (ZZUi007-A) from a 52-year-old
      patient with a novel CHCHD2 gene mutation in Parkinson's disease.
AB  - CHCHD2 mutation has been reported as a potential cause of a rare form of familial
      Parkinson's disease. Recently, a novel CHCHD2 mutation was identified in a family
      with Parkinson's disease. The dermal fibroblasts of the patient were obtained and
      successfully transformed into induced pluripotent stem cells(iPSCs), employing
      episomal plasmids expressing OCT3/4, SOX2, KLF4, LIN28, and L-MYC. Our model may
      offer a good platform for further research on the pathomechanism, drug testing,
      and gene therapy of this disease. RESOURCE TABLE: RESOURCE UTILITY: CHCHD2
      mutation has been shown to be associated with Parkinson's disease (PD) (Shi et
      al., 2016). Induced pluripotent stem cells (iPSCs), generated from a patient
      harboring a CHCHD2 mutation, may provide an ideal cell model for exploring the
      pathogenesis of this disease and aid in drug screening. RESOURCE DETAILS:
      Parkinson's disease (PD) is one of the most common neurodegenerative disorders,
      characterized by resting tremors, muscular rigidity, bradykinesia, and postural
      instability. Previous studies have revealed that parkinsonism can be caused by
      mutations in several genes including parkin, PTEN-induced putative kinase protein
      1 (PINK1), parkinsonism-associated deglycase (DJ1), and ATPase 13A2 (ATP13A2)
      (Bonifati, 2014). In this study, a novel CHCHD2 mutation was identified in a
      family with Parkinson's disease (Shi et al., 2016), and the fibroblasts of the
      patient were successfully transformed into iPSCs. Episomal plasmids were used to
      generate the ZZUi007-A iPSC line (Fig. 1A). Pluripotency markers were examined
      via immunocytochemical staining using antibodies against human OCT-4, TRA-1-60
      and Nanog (Fig. 1B). Flow cytometric analysis showed that more than 99% of the
      cells expressed OCT-4 and TRA-1-60 (Fig. 1C). The karyotype of CHCHD2-01 iPSCs
      was numerically and structurally normal (Fig. 1D). The mutation (c.182C > T;
      p.Thr61Ile) in CHCHD2 was confirmed by Sanger sequencing in the newly established
      iPSC line (Fig. 1E). Episomal plasmids were detected by polymerase chain reaction
      (PCR) using episomal plasmid-specific primers and disappeared from passage 15
      (Fig. 1F). Furthermore, the iPSC line had the potential to differentiate into
      cells of all three germ layers in vivo (Fig. 1G).

PMID- 30237141
TI  - Characterizing the role of SWI/SNF-related chromatin remodeling complexes in
      planarian regeneration and stem cell function.
AB  - SWI/SNF-related chromatin remodeling complexes, including the human BAF and PBAF
      complexes, are involved in controlling stem cell pluripotency and differentiation
      in many species. However, these complexes have not been fully characterized in
      planarians, an emerging model for the in vivo study of stem cells. These
      flatworms have the ability to regenerate following injury or amputation, and we
      sought to investigate the role of chromatin remodeling in this process through
      bioinformatic and genetic characterization of the SWI/SNF-like complexes in
      Schmidtea mediterranea. We identified planarian homologs of all human BAF and
      PBAF subunits, and then examined their expression patterns and RNAi phenotypes.
      We found that the genes are expressed in both stem cells and differentiated
      tissues, and their knockdown results in impaired regeneration and other
      phenotypes indicating stem cell dysfunction. Knockdown of core complex members
      and Smed-ARID1 led to an increase in steady-state mitotic cell number, however,
      the stereotypical proliferative response that follows amputation was reduced
      following Smed-BRG1/BRM-2 RNAi. The number of differentiating epidermal lineage
      cells and expression of epidermal and muscle lineage markers were also reduced
      following SWI/SNF knockdown. Our findings provide insight into the importance of
      the SWI/SNF complex in stem cell function and cellular differentiation in
      planarians.

PMID- 30237142
TI  - A quasi in situ TEM grid reactor for decoupling catalytic gas phase reactions and
      analysis.
AB  - We present a versatile grid reactor setup for transmission electron microscopy
      (TEM), which is able to track catalytic conversion on TEM amounts of sample. It
      is based on the concept of decoupling catalytic gas-phase reactions from the
      structural analysis of identical particles before and after reaction. The system
      has superior properties in terms of image resolution and long-term measurements
      compared to conventional in situ TEM analysis. Monitoring catalytic conversions
      on a TEM grid is enabled by proton-transfer reaction mass spectrometry. In
      addition, identical location imaging benefits from a secure transfer of the
      sample between TEM and the reactor system by vacuum transfer holders. Using Pt
      and Cu/ZnO/Al2O3 as an example we show that structural changes of identical
      particles or areas of a Pt foil before and after reactive experiments can be
      tracked. During catalytic testing the samples are exposed to homogeneous reaction
      conditions. The concept minimizes electron-sample and electron-atmosphere
      interactions and can prospectively be considered as complementary tool to in situ
      TEM analysis.

PMID- 30237143
TI  - Blind identification of magnetic signals in electron magnetic chiral dichroism
      using independent component analysis.
AB  - Electron magnetic chiral dichroism (EMCD) is a promising technique to investigate
      local magnetic structures in the electron microscope. However, recognition of the
      EMCD signal, or also finding optimal parameter settings for given materials and
      sample orientations typically requires extensive simulations to aid the
      experiment. Here, we discuss how modern data processing techniques, in particular
      independent component analysis, can be used to identify magnetic signals in an
      unsupervised manner from energy filtered transmission electron microscopy (EFTEM)
      images. On the background of the recent advent of 4D scanning transmission
      electron microscopy, we discuss how this data processing may enable simultaneous
      tracking of all three spatial components of the magnetic momenta for arbitrary
      materials and several sample orientations without the previous need of
      complementary simulations.

PMID- 30237144
TI  - Accurate determination of low-symmetry Bravais unit cells by EBSD.
AB  - Unit cells lack of symmetry are difficult to determine accurately, compared to
      high-symmetry unit cells with many constraints. The electron backscatter
      diffraction (EBSD) technique in scanning electron microscopy (SEM) was considered
      inadequate for this task because of the highly defective band detections. We
      develop a new method for the Kikuchi-band detections, which can improve the
      accuracy of the EBSD technique in determining the lattice constants of totally
      unknown Bravais unit cells with low symmetry. The results show that, under ideal
      conditions (i.e., low-noise EBSD patterns and known projection center), the
      relative error of the unit-cell constants (a, b, c) is less than 0.3%, and that
      of the axial ratios (a/b, b/c, c/a) is less than 0.5%. The absolute errors of the
      inter-axial angles (alpha, beta, gamma) and crystal orientations are about 0.1
      degrees . Our method is perhaps not as accurate as the classical techniques such
      as X-ray diffraction, but is demonstrated as a practical tool for
      crystallographic characterization especially on low-fraction phases, and could be
      easily incorporated into an SEM to make the most of the SEM in the area of
      microanalysis.

PMID- 30237145
TI  - Efficient multi-kernel multi-instance learning using weakly supervised and
      imbalanced data for diabetic retinopathy diagnosis.
AB  - OBJECTIVE: Diabetic retinopathy (DR) is one of the most serious complications of
      diabetes. Early detection and treatment of DR are key public health interventions
      that can significantly reduce the risk of vision loss. How to effectively screen
      and diagnose the retinal fundus image in order to identify retinopathy in time is
      a major challenge. In the traditional DR screening system, the accuracy of micro
      aneurysm (MA) and hemorrhagic (H) lesion detection determines the final screening
      performance. The detection method produced a large number of false positive
      samples for guaranteeing high sensitivity, and the classification model was not
      effective in removing false positives since the suspicious lesions lack label
      information. METHODS: In order to solve the problem of supervised learning in the
      diagnosis of DR, we formulate weakly supervised multi-class DR grading as a multi
      class multi-instance problem where each image (bag) is labeled as healthy or
      abnormal and consists of unlabeled candidate lesion regions (instances).
      Specifically, we proposed a multi-kernel multi-instance learning method based on
      graph kernel. Moreover, we develop an under-sampling from instance level and over
      sampling from bag level to improve the performance of the multi-instance learning
      in the diagnosis of DR. RESULTS: Through empirical evaluation and comparison with
      different baselinemethods and the state-of-the-art methods on data from Messidor,
      we illustrate that the proposed method reports favorable results, with an overall
      classification accuracy of 0.916 and an AUC of 0.957. CONCLUSIONS: The
      experiments results demonstrate that the proposed multi-kernel multi-instance
      learning framework with bi-level re-sampling can solve the problem in the
      imbalanced and weakly supervised data for grading diabetic retinopathy, and it
      improves the diagnosis performance over several state-of-the-art competing
      methods.

PMID- 30237146
TI  - Optimal multi-object segmentation with novel gradient vector flow based shape
      priors.
AB  - Shape priors have been widely utilized in medical image segmentation to improve
      segmentation accuracy and robustness. A major way to encode such a prior shape
      model is to use a mesh representation, which is prone to causing self
      intersection or mesh folding. Those problems require complex and expensive
      algorithms to mitigate. In this paper, we propose a novel shape prior directly
      embedded in the voxel grid space, based on gradient vector flows of a pre
      segmentation. The flexible and powerful prior shape representation is ready to be
      extended to simultaneously segmenting multiple interacting objects with minimum
      separation distance constraint. The segmentation problem of multiple interacting
      objects with shape priors is formulated as a Markov Random Field problem, which
      seeks to optimize the label assignment (objects or background) for each voxel
      while keeping the label consistency between the neighboring voxels. The
      optimization problem can be efficiently solved with a single minimum s-t cut in
      an appropriately constructed graph. The proposed algorithm has been validated on
      two multi-object segmentation applications: the brain tissue segmentation in MRI
      images and the bladder/prostate segmentation in CT images. Both sets of
      experiments showed superior or competitive performance of the proposed method to
      the compared state-of-the-art methods.

PMID- 30237147
TI  - High-Sensitivity Troponin and the Selection of Patients for Cardiac Imaging in
      the Outpatient Clinic.

PMID- 30237148
TI  - Systematic Comparison of Bacterial Colonization of Endometrial Tissue and Fluid
      Samples in Recurrent Miscarriage Patients: Implications for Future Endometrial
      Microbiome Studies.
AB  - BACKGROUND: A recent study has reported that the microbiota in endometrial fluid
      of patients receiving in vitro fertilization and embryo transfer (IVF-ET) may
      predict implantation and pregnancy rates. However, studies are lacking that
      simultaneously compare the microbiota between endometrial fluid and tissue
      samples. Whether the microbiota composition in endometrial fluid reflects that in
      the endometrial tissue remains unclear. METHODS: We systematically profiled the
      microbiota in endometrial fluid and tissue samples of IVF-ET patients using
      massively parallel sequencing. The bacterial 16S ribosomal RNA gene (V4 region)
      was PCR-amplified. Sequencing reads with >98% nucleotide identity were clustered
      as a bacterial taxon. To account for the different number of reads per sample, we
      normalized the read counts of each taxon before comparing its relative abundances
      across samples. RESULTS: Thirteen taxa, including Verrucomicrobiaceae,
      Brevundimonas, Achromobacter, Exiguobacterium, and Flavobacterium, were
      consistently detected only in endometrial tissue samples but not fluid samples.
      Eight taxa were detected in fluid but not tissue. Twenty-two taxa were
      differentially abundant between fluid and tissue samples (adjusted P values, 4.1
      * 10-25 to 0.025). The numbers of taxa identified per 1000 sequencing reads,
      diversity, and evenness in fluid samples were smaller than those in tissue
      samples. CONCLUSIONS: Our data suggest that the microbiota composition in
      endometrial fluid does not fully reflect that in endometrial tissue. Sampling
      from both endometrial fluid and biopsy allows a more comprehensive view of
      microbial colonization. Further efforts are needed to identify the preanalytical
      effects, including sampling sites, methods, and sequencing depth, on profiling
      endometrial microbiota.

PMID- 30237150
TI  - Completeness of Reporting of Systematic Reviews of Diagnostic Test Accuracy Based
      on the PRISMA-DTA Reporting Guideline.
AB  - BACKGROUND: We evaluated the completeness of reporting of diagnostic test
      accuracy (DTA) systematic reviews using the recently developed Preferred
      Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA)-DTA guidelines.
      METHODS: MEDLINE(r) was searched for DTA systematic reviews published October
      2017 to January 2018. The search time span was modulated to reach the desired
      sample size of 100 systematic reviews. Reporting on a per-item basis using PRISMA
      DTA was evaluated. RESULTS: One hundred reviews were included. Mean reported
      items were 18.6 of 26 (71%; SD = 1.9) for PRISMA-DTA and 5.5 of 11 (50%; SD =
      1.2) for PRISMA-DTA for abstracts. Items in the results were frequently reported.
      Items related to protocol registration, characteristics of included studies,
      results synthesis, and definitions used in data extraction were infrequently
      reported. Infrequently reported items from PRISMA-DTA for abstracts included
      funding information, strengths and limitations, characteristics of included
      studies, and assessment of applicability. Reporting completeness was higher in
      higher impact factor journals (18.9 vs 18.1 items; P = 0.04), studies that cited
      PRISMA (18.9 vs 17.7 items; P = 0.003), or used supplementary material (19.1 vs
      18.0 items; P = 0.004). Variability in reporting was associated with author
      country (P = 0.04) but not journal (P = 0.6), abstract word count limitations (P
      = 0.9), PRISMA adoption (P = 0.2), structured abstracts (P = 0.2), study design
      (P = 0.8), subspecialty area (P = 0.09), or index test (P = 0.5). Abstracts with
      a higher word count were more informative (R = 0.4; P < 0.001). No association
      with word counts was observed for full-text reports (R = -0.03; P = 0.06).
      CONCLUSIONS: Recently published reports of DTA systematic reviews are not fully
      informative when evaluated against the PRISMA-DTA guidelines. These results
      should guide knowledge translation strategies, including journal level (e.g.,
      PRISMA-DTA adoption, increased abstract word count, and use of supplementary
      material) and author level (PRISMA-DTA citation awareness) strategies.

PMID- 30237151
TI  - Machine Learning in Clinical Pathology: Seeing the Forest for the Trees.

PMID- 30237149
TI  - Applying Standard Clinical Chemistry Assay Validation to Droplet Digital PCR
      Quantitative Liquid Biopsy Testing.
AB  - BACKGROUND: Droplet digital PCR (ddPCR) is an emerging technology for
      quantitative cell-free DNA oncology applications. However, assay performance
      criteria must be established in a standardized manner to harness this potential.
      We reasoned that standard protocols used in clinical chemistry assay validation
      should be able to fill this need. METHODS: We validated KRAS, EGFR, and BRAF
      quantitative ddPCR assays based on the Clinical Laboratory Improvement Act
      regulations for laboratory-developed tests in clinical chemistry and the matching
      Clinical and Laboratory Standards Institute guidelines. This included evaluation
      of limit of the blank (LOB), limit of detection (LOD), limit of quantification
      (LOQ), intraassay and interassay imprecision, analytical range, dilution
      linearity, accuracy (including comparison with orthogonal platforms), reference
      range study, interference, and stability studies. RESULTS: For the ddPCR assays,
      the LOB was 4 mutant copies, LODs were 12 to 22 copies, and LOQs were 35 to 64
      copies. The upper limit of the dynamic range was 30000 copies, and dilutions were
      linear down to the LOQs with good accuracy of spike recovery of Horizon reference
      material. Method comparisons with next-generation sequencing and an alternative
      ddPCR platform showed complete qualitative agreement and quantitative
      concordance, with slopes of 0.73 to 0.97 and R 2s of 0.83 to 0.99. No substantial
      interferences were discovered. Wild-type copy numbers in plasma ranged from 462
      to 6169/mL in healthy individuals. CONCLUSIONS: Standard clinical chemistry assay
      validation protocols can be applied to quantitative ddPCR assays. This should
      facilitate comparison of the performance of different assays and allow
      establishment of minimal significant change thresholds in monitoring
      applications.

PMID- 30237152
TI  - Cochrane director says his sacking was flawed and came after "show trial".

PMID- 30237153
TI  - Interaction of mammalian and plant H+/sucrose transporters with 14-3-3 proteins.
AB  - The solute carrier 45 family (SLC45) was defined in the course of the Human
      Genome Project and consists of four members, A1-A4, which show only 20-30%
      identity of amino acid sequences among each other. All these members exhibit an
      identity of ~20% to plant H+/sucrose cotransporters. Recently, we expressed
      members of the murine SLC45 family in yeast cells and demonstrated that they are,
      like their plant counterparts, H+/sucrose cotransporters. In contrast with the
      plant proteins, SLC45 transporters recognise also the monosaccharides glucose and
      fructose as physiological substrates and seem to be involved in alternative sugar
      supply as well as in osmoregulation of several mammalian tissues. In the present
      study, we provide novel insights into the regulation of SLC45 transporters. By
      screening for interaction partners, we found a 14-3-3 protein as a promising
      candidate for control of transport activity. Indeed, co-expression of the gamma
      isoform of murine 14-3-3 protein in yeast and Xenopus oocytes led to a
      significant decrease in transport rates of the murine SLC45 transporters as well
      as of the plant H+/sucrose transporter Sut1.

PMID- 30237154
TI  - Promising activity of nelfinavir-bortezomib-dexamethasone in proteasome inhibitor
      refractory multiple myeloma.

PMID- 30237155
TI  - Reduced incidence of vein occlusion and postthrombotic syndrome after immediate
      compression for deep vein thrombosis.
AB  - Thus far, the association between residual vein occlusion and immediate
      compression therapy and postthrombotic syndrome is undetermined. Therefore, we
      investigated whether compression therapy immediately after diagnosis of deep vein
      thrombosis affects the occurrence of residual vein obstruction (RVO), and whether
      the presence of RVO is associated with postthrombotic syndrome and recurrent
      venous thromboembolism. In a prespecified substudy within the IDEAL
      (individualized duration of elastic compression therapy against long-term
      duration of therapy for prevention of postthrombotic syndrome) deep vein
      thrombosis (DVT) study, 592 adult patients from 10 academic and nonacademic
      centers across The Netherlands, with objectively confirmed proximal DVT of the
      leg, received no compression or acute compression within 24 hours of diagnosis of
      DVT with either multilayer bandaging or compression hosiery (pressure, 35 mm Hg).
      Presence of RVO and recurrent venous thromboembolism was confirmed with
      compression ultrasonography and incidence of postthrombotic syndrome as a
      Villalta score of at least 5 at 6 and 24 months. The average time from diagnosis
      until assessment of RVO was 5.3 (standard deviation, 1.9) months. A significantly
      lower percentage of patients who did receive compression therapy immediately
      after DVT had RVO (46.3% vs 66.7%; odds ratio, 0.46; 95% confidence interval,
      0.27-0.80; P = .005). Postthrombotic syndrome was less prevalent in patients
      without RVO (46.0% vs 54.0%; odds ratio, 0.65; 95% confidence interval, 0.46
      0.92; P = .013). Recurrent venous thrombosis showed no significant association
      with RVO. Immediate compression should therefore be offered to all patients with
      acute DVT of the leg, irrespective of severity of complaints. This study was
      registered at ClinicalTrials.gov (NCT01429714) and the Dutch Trial registry in
      November 2010 (NTR2597).

PMID- 30237156
TI  - Human dignity and gene editing: Using human dignity as an argument against
      modifying the human genome and germline is a logical fallacy.

PMID- 30237158
TI  - In This Issue of Diabetes.

PMID- 30237157
TI  - Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral
      alterations.
AB  - The 1555 A to G substitution in mitochondrial 12S A-site rRNA is associated with
      maternally transmitted deafness of variable penetrance in the absence of
      otherwise overt disease. Here, we recapitulate the suggested A1555G-mediated
      pathomechanism in an experimental model of mitoribosomal mistranslation by
      directed mutagenesis of mitoribosomal protein MRPS5. We first establish that the
      ratio of cysteine/methionine incorporation and read-through of mtDNA-encoded MT
      CO1 protein constitute reliable measures of mitoribosomal misreading. Next, we
      demonstrate that human HEK293 cells expressing mutant V336Y MRPS5 show increased
      mitoribosomal mistranslation. As for immortalized lymphocytes of individuals with
      the pathogenic A1555G mutation, we find little changes in the transcriptome of
      mutant V336Y MRPS5 HEK cells, except for a coordinated upregulation of
      transcripts for cytoplasmic ribosomal proteins. Homozygous knock-in mutant Mrps5
      V338Y mice show impaired mitochondrial function and a phenotype composed of
      enhanced susceptibility to noise-induced hearing damage and anxiety-related
      behavioral alterations. The experimental data in V338Y mutant mice point to a key
      role of mitochondrial translation and function in stress-related behavioral and
      physiological adaptations.

PMID- 30237160
TI  - Epigenetics and Epigenomics: Implications for Diabetes and Obesity.
AB  - The American Diabetes Association convened a research symposium, "Epigenetics and
      Epigenomics: Implications for Diabetes and Obesity" on 17-19 November 2017.
      International experts in genetics, epigenetics, computational biology, and
      physiology discussed the current state of understanding of the relationships
      between genetics, epigenetics, and environment in diabetes and examined existing
      evidence for the role of epigenetic factors in regulating metabolism and the risk
      of diabetes and its complications. The authors summarize the presentations, which
      highlight how the complex interactions between genes and environment may in part
      be mediated through epigenetic changes and how information about nutritional and
      other environmental stimuli can be transmitted to the next generation. In
      addition, the authors present expert consensus on knowledge gaps and research
      recommendations for the field.

PMID- 30237161
TI  - Fatty Acids and Insulin Secretion: From FFAR and Near?

PMID- 30237159
TI  - A Global Overview of Precision Medicine in Type 2 Diabetes.
AB  - The detailed characterization of human biology and behaviors is now possible at
      scale owing to innovations in biomarkers, bioimaging, and wearable technologies;
      "big data" from electronic medical records, health insurance databases, and other
      platforms becoming increasingly accessible; and rapidly evolving computational
      power and bioinformatics methods. Collectively, these advances are creating
      unprecedented opportunities to better understand diabetes and many other complex
      traits. Identifying hidden structures within these complex data sets and linking
      these structures to outcome data may yield unique insights into the risk factors
      and natural history of diabetes, which in turn may help optimize the prevention
      and management of the disease. This emerging area is broadly termed "precision
      medicine." In this Perspective, we give an overview of the evidence and barriers
      to the development and implementation of precision medicine in type 2 diabetes.
      We also discuss recently presented paradigms through which complex data might
      enhance our understanding of diabetes and ultimately our ability to tackle the
      disease more effectively than ever before.

PMID- 30237163
TI  - Gene regulation by a glycine riboswitch singlet uses a finely tuned energetic
      landscape for helical switching.
AB  - Riboswitches contain structured aptamer domains that, upon ligand binding,
      facilitate helical switching in their downstream expression platforms to alter
      gene expression. To fully dissect how riboswitches function requires a better
      understanding of the energetic landscape for helical switching. Here, we report a
      sequencing-based high-throughput assay for monitoring in vitro transcription
      termination and use it to simultaneously characterize the functional effects of
      all 522 single point mutants of a glycine riboswitch type-1 singlet. Mutations
      throughout the riboswitch cause ligand-dependent defects, but only mutations
      within the terminator hairpin alter readthrough efficiencies in the absence of
      ligand. A comprehensive analysis of the expression platform reveals that ligand
      binding stabilizes the antiterminator by just 2-3 kcal/mol, indicating that the
      competing expression platform helices must be extremely close in energy to elicit
      a significant ligand-dependent response. These results demonstrate that gene
      regulation by this riboswitch is highly constrained by the energetics of ligand
      binding and conformational switching. These findings exemplify the energetic
      parameters of RNA conformational rearrangements driven by binding events.

PMID- 30237164
TI  - OSBP-related protein 4L promotes phospholipase Cbeta3 translocation from the
      nucleus to the plasma membrane in Jurkat T-cells.
AB  - Phosphoinositide phospholipases C (PLCs) are a family of eukaryotic intracellular
      enzymes with important roles in signal transduction. In addition to their
      location at the plasma membrane, PLCs also exist within the cell nucleus where
      they are stored. We previously demonstrated that OSBP-related protein 4L (ORP4L)
      anchors cluster of differentiation 3epsilon (CD3epsilon) to the heterotrimeric G
      protein subunit (Galphaq/11) to control PLCbeta3 relocation and activation.
      However, the underlying mechanism by which ORP4L facilitates PLCbeta3
      translocation remains unknown. Here, using confocal immunofluorescence microscopy
      and coimmunoprecipitation assays, we report that ORP4L stimulates PLCbeta3
      translocation from the nucleus to the plasma membrane in Jurkat T-cells in two
      steps. First, we found that ORP4L is required for the activation of Ras-related
      nuclear protein (RAN), a GTP-binding nuclear protein that binds to exportin 1 and
      eventually promotes the nuclear export of PLCbeta3. Second, we also observed that
      ORP4L interacts with vesicle-associated membrane protein-associated protein A
      (VAPA) through its two phenylalanines in an acidic tract (FFAT) motif. This
      complex enabled PLCbeta3 movement to the plasma membrane, indicating that
      PLCbeta3 translocation occurs in a VAPA-dependent manner. This study reveals
      detailed mechanistic insight into the role of ORP4L in PLCbeta3 redistribution
      from storage within the nucleus to the plasma membrane via RAN activation and
      interaction with VAPA in Jurkat T-cells.

PMID- 30237165
TI  - The intracellular parasite Toxoplasma gondii harbors three druggable FNT-type
      formate and l-lactate transporters in the plasma membrane.
AB  - Toxoplasma gondii is a globally prevalent parasitic protist. It is well-known for
      its ability to infect almost all nucleated vertebrate cells, which is reflected
      by its unique metabolic architecture. Its fast-growing tachyzoite stage
      catabolizes glucose via glycolysis to yield l-lactate as a major by-product that
      must be exported from the cell to prevent toxicity; the underlying mechanism
      remains to be elucidated, however. Herein, we report three formate-nitrite
      transporter (FNT)-type monocarboxylate/proton symporters located in the plasma
      membrane of the T. gondii tachyzoite stage. We observed that all three proteins
      transport both l-lactate and formate in a pH-dependent manner and are inhibited
      by 2-hydroxy-chromanones (a class of small synthetic molecules). We also show
      that these compounds pharmacologically inhibit T. gondii growth. Using a chemical
      biology approach, we identified the critical residues in the substrate
      selectivity region of the parasite transporters that determine differential
      specificity and sensitivity toward both substrates and inhibitors. Our findings
      further indicate that substrate specificity in FNT family proteins from T. gondii
      has evolved such that a functional repurposing of prokaryotic-type transporters
      helps fulfill a critical metabolic role in a clinically important parasitic
      protist. In summary, we have identified and characterized the lactate
      transporters of T. gondii and have shown that compounds blocking the FNTs in this
      parasite can inhibit its growth, suggesting that these transporters could have
      utility as potential drug targets.

PMID- 30237167
TI  - Biochemical characterization of the PHARC-associated serine hydrolase ABHD12
      reveals its preference for very-long-chain lipids.
AB  - Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC)
      is a rare genetic human neurological disorder caused by null mutations to the
      Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12.
      Although the role that ABHD12 plays in PHARC is understood, the thorough
      biochemical characterization of ABHD12 is lacking. Here, we report the facile
      synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and
      unsaturation and use this lipid substrate library to biochemically characterize
      recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested
      that this enzyme requires glycosylation for optimal activity and that it has a
      strong preference for very-long-chain lipid substrates. We further validated this
      substrate profile against brain membrane lysates generated from WT and ABHD12
      knockout mice. Finally, using cellular organelle fractionation and
      immunofluorescence assays, we show that mammalian ABHD12 is enriched on the
      endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are
      biosynthesized in cells. Taken together, our findings provide a biochemical
      explanation for why very-long-chain lipids (such as lysophosphatidylserine
      lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model
      of PHARC.

PMID- 30237166
TI  - A partial reconstitution implicates DltD in catalyzing lipoteichoic acid d
      alanylation.
AB  - Modifications to the Gram-positive bacterial cell wall play important roles in
      antibiotic resistance and pathogenesis, but the pathway for the d-alanylation of
      teichoic acids (DLT pathway), a ubiquitous modification, is poorly understood.
      The d-alanylation machinery includes two membrane proteins of unclear function,
      DltB and DltD, which are somehow involved in transfer of d-alanine from a carrier
      protein inside the cell to teichoic acids on the cell surface. Here, we probed
      the role of DltD in the human pathogen Staphylococcus aureus using both cell
      based and biochemical assays. We first exploited a known synthetic lethal
      interaction to establish the essentiality of each gene in the DLT pathway for d
      alanylation of lipoteichoic acid (LTA) and confirmed this by directly detecting
      radiolabeled d-Ala-LTA both in cells and in vesicles prepared from mutant strains
      of S. aureus We developed a partial reconstitution of the pathway by using cell
      derived vesicles containing DltB, but no other components of the d-alanylation
      pathway, and showed that d-alanylation of previously formed lipoteichoic acid in
      the DltB vesicles requires the presence of purified and reconstituted DltA, DltC,
      and DltD, but not of the LTA synthase LtaS. Finally, based on the activity of
      DltD mutants in cells and in our reconstituted system, we determined that Ser-70
      and His-361 are essential for d-alanylation activity, and we propose that DltD
      uses a catalytic dyad to transfer d-alanine to LTA. In summary, we have developed
      a suite of assays for investigating the bacterial DLT pathway and uncovered a
      role for DltD in LTA d-alanylation.

PMID- 30237168
TI  - Membrane curvature allosterically regulates the phosphatidylinositol cycle,
      controlling its rate and acyl-chain composition of its lipid intermediates.
AB  - Signaling events at membranes are often mediated by membrane lipid composition or
      membrane physical properties. These membrane properties could act either by
      favoring the membrane binding of downstream effectors or by modulating their
      activity. Several proteins can sense/generate membrane physical curvature (i.e.
      shape). However, the modulation of the activity of enzymes by a membrane's shape
      has not yet been reported. Here, using a cell-free assay with purified
      diacylglycerol kinase epsilon (DGKepsilon) and liposomes, we studied the activity
      and acyl-chain specificity of an enzyme of the phosphatidylinositol (PI) cycle,
      DGKepsilon. By systematically varying the model membrane lipid composition and
      physical properties, we found that DGKepsilon has low activity and lacks acyl
      chain specificity in locally flat membranes, regardless of the lipid composition.
      On the other hand, these enzyme properties were greatly enhanced in membrane
      structures with a negative Gaussian curvature. We also found that this is not a
      consequence of preferential binding of the enzyme to those structures, but rather
      is due to a curvature-mediated allosteric regulation of DGKepsilon activity and
      acyl-chain specificity. Moreover, in a fine-tuned interplay between the enzyme
      and the membrane, DGKepsilon favored the formation of structures with greater
      Gaussian curvature. DGKepsilon does not bear a regulatory domain, and these
      findings reveal the importance of membrane curvature in regulating DGKepsilon
      activity and acyl-chain specificity. Hence, this study highlights that a
      hierarchic coupling of membrane physical property and lipid composition
      synergistically regulates membrane signaling events. We propose that this
      regulatory mechanism of membrane-associated enzyme activity is likely more common
      than is currently appreciated.

PMID- 30237169
TI  - The properties of Msh2-Msh6 ATP binding mutants suggest a signal amplification
      mechanism in DNA mismatch repair.
AB  - DNA mismatch repair (MMR) corrects mispaired DNA bases and small
      insertion/deletion loops generated by DNA replication errors. After binding a
      mispair, the eukaryotic mispair recognition complex Msh2-Msh6 binds ATP in both
      of its nucleotide-binding sites, which induces a conformational change resulting
      in the formation of an Msh2-Msh6 sliding clamp that releases from the mispair and
      slides freely along the DNA. However, the roles that Msh2-Msh6 sliding clamps
      play in MMR remain poorly understood. Here, using Saccharomyces cerevisiae, we
      created Msh2 and Msh6 Walker A nucleotide-binding site mutants that have defects
      in ATP binding in one or both nucleotide-binding sites of the Msh2-Msh6
      heterodimer. We found that these mutations cause a complete MMR defect in vivo
      The mutant Msh2-Msh6 complexes exhibited normal mispair recognition and were
      proficient at recruiting the MMR endonuclease Mlh1-Pms1 to mispaired DNA. At
      physiological (2.5 mm) ATP concentration, the mutant complexes displayed modest
      partial defects in supporting MMR in reconstituted Mlh1-Pms1-independent and Mlh1
      Pms1-dependent MMR reactions in vitro and in activation of the Mlh1-Pms1
      endonuclease and showed a more severe defect at low (0.1 mm) ATP concentration.
      In contrast, five of the mutants were completely defective and one was mostly
      defective for sliding clamp formation at high and low ATP concentrations. These
      findings suggest that mispair-dependent sliding clamp formation triggers binding
      of additional Msh2-Msh6 complexes and that further recruitment of additional
      downstream MMR proteins is required for signal amplification of mispair binding
      during MMR.

PMID- 30237170
TI  - ROS-induced HSP70 promotes cytoplasmic translocation of high-mobility group box
      1b and stimulates antiviral autophagy in grass carp kidney cells.
AB  - Autophagy plays many physiological and pathophysiological roles. However, the
      roles and the regulatory mechanisms of autophagy in response to viral infections
      are poorly defined in teleost fish, such as grass carp (Ctenopharyngodon idella),
      which is one of the most important aquaculture species in China. In this study,
      we found that both grass carp reovirus (GCRV) infection and hydrogen peroxide
      (H2O2) treatment induced the accumulation of reactive oxygen species (ROS) in C.
      idella kidney cells and stimulate autophagy. Suppressing ROS accumulation with N
      acetyl-l-cysteine significantly inhibited GCRV-induced autophagy activation and
      enhanced GCRV replication. Although ROS-induced autophagy, in turn, restricted
      GCRV replication, further investigation revealed that the multifunctional
      cellular protein high-mobility group box 1b (HMGB1b) serves as a heat shock
      protein 70 (HSP70)-dependent, pro-autophagic protein in grass carp. Upon H2O2
      treatment, cytoplasmic HSP70 translocated to the nucleus, where it interacted
      with HMGB1b and promoted cytoplasmic translocation of HMGB1b. Overexpression and
      siRNA-mediated knockdown assays indicated that HSP70 and HMGB1b synergistically
      enhance ROS-induced autophagic activation in the cytoplasm. Moreover, HSP70
      reinforced an association of HMGB1b with the C. idella ortholog of Beclin 1 (a
      mammalian ortholog of the autophagy-associated yeast protein ATG6) by directly
      interacting with C. idella Beclin 1. In summary, this study highlights the
      antiviral function of ROS-induced autophagy in response to GCRV infection and
      reveals the positive role of HSP70 in HMGB1b-mediated autophagy initiation in
      teleost fish.

PMID- 30237171
TI  - Functional and phylogenetic characterization of noncanonical vitamin B12-binding
      proteins in zebrafish suggests involvement in cobalamin transport.
AB  - In humans, transport of food-derived cobalamin (vitamin B12) from the digestive
      system into the bloodstream involves three paralogous proteins: transcobalamin
      (TC), haptocorrin (HC), and intrinsic factor (IF). Each of these proteins
      contains two domains, an alpha-domain and a beta-domain, which together form a
      cleft in which cobalamin binds. Zebrafish (Danio rerio) are thought to possess
      only a single cobalamin transport protein, referred to as Tcn2, which is a
      transcobalamin homolog. Here, we used CRISPR/Cas9 mutagenesis to create null
      alleles of tcn2 in zebrafish. Fish homozygous for tcn2-null alleles were viable
      and exhibited no obvious developmentally or behaviorally abnormal phenotypes. For
      this reason, we hypothesized that previously unidentified cobalamin-carrier
      proteins encoded in the zebrafish genome may provide an additional pathway for
      cobalamin transport. We identified genes predicted to code for two such proteins,
      Tcn-beta-a (Tcnba) and Tcn-beta-b (Tcnbb), which differ from all previously
      characterized cobalamin transport proteins as they lack the alpha-domain. These
      beta-domain-only proteins are representative of an undescribed class of cobalamin
      carrier proteins that are highly conserved throughout the ray-finned fishes. We
      observed that the genes encoding the three cobalamin transport homologs, tcn2,
      tcnba, and tcnbb, are expressed in unique spatial and temporal patterns in the
      developing zebrafish. Moreover, exogenously expressed recombinant Tcnba and Tcnbb
      bound cobalamin with high affinity, comparable with binding by full-length Tcn2.
      Taken together, our results suggest that this noncanonical protein structure has
      evolved to fully function as a cobalamin-carrier protein, thereby allowing for a
      compensatory cobalamin transport mechanism in the tcn2 -/- zebrafish.

PMID- 30237172
TI  - Hydrogen sulfide bypasses the rate-limiting oxygen activation of heme oxygenase.
AB  - Discovery of unidentified protein functions is of biological importance because
      it often provides new paradigms for many research areas. Mammalian heme oxygenase
      (HO) enzyme catalyzes the O2-dependent degradation of heme into carbon monoxide
      (CO), iron, and biliverdin through numerous reaction intermediates. Here, we
      report that H2S, a gaseous signaling molecule, is part of a novel reaction
      pathway that drastically alters HO's products, reaction mechanism, and catalytic
      properties. Our prediction of this interplay is based on the unique reactivity of
      H2S with one of the HO intermediates. We found that in the presence of H2S, HO
      produces new linear tetrapyrroles, which we identified as isomers of sulfur
      containing biliverdin (SBV), and that only H2S, but not GSH, cysteine, and
      polysulfides, induces SBV formation. As BV is converted to bilirubin (BR), SBV is
      enzymatically reduced to sulfur-containing bilirubin (SBR), which shares similar
      properties such as antioxidative effects with normal BR. SBR was detected in
      culture media of mouse macrophages, confirming the existence of this H2S-induced
      reaction in mammalian cells. H2S reacted specifically with a ferric verdoheme
      intermediate of HO, and verdoheme cleavage proceeded through an O2-independent
      hydrolysis-like mechanism. This change in activation mode diminished O2
      dependence of the overall HO activity, circumventing the rate-limiting O2
      activation of HO. We propose that H2S could largely affect O2 sensing by
      mammalian HO, which is supposed to relay hypoxic signals by decreasing CO output
      to regulate cellular functions. Moreover, the novel H2S-induced reaction
      identified here helps sustain HO's heme-degrading and antioxidant-generating
      capacity under highly hypoxic conditions.

PMID- 30237173
TI  - Functional dissection of the N-terminal extracellular domains of Frizzled 6
      reveals their roles for receptor localization and Dishevelled recruitment.
AB  - The Frizzled (FZD) proteins belong to class F of G protein-coupled receptors
      (GPCRs) and are essential for various pathways involving the secreted
      lipoglycoproteins of the wingless/int-1 (WNT) family. A WNT-binding cysteine-rich
      domain (CRD) in FZDs is N-terminally located and connected to the seven
      transmembrane domain-spanning receptor core by a linker domain that has a
      variable length in different FZD homologs. However, the function and importance
      of this linker domain are poorly understood. Here we used systematic mutagenesis
      of FZD6 to define the minimal N-terminal domain sufficient for receptor surface
      expression and recruitment of the intracellular scaffold protein Dishevelled
      (DVL). Further, we identified a triad of evolutionarily conserved cysteines in
      the FZD linker domain that is crucial for receptor membrane expression and
      recruitment of DVL. Our results are in agreement with the concept that the
      conserved cysteines in the linker domain of FZDs assist with the formation of a
      common secondary structure in this region. We propose that this structure could
      be involved in agonist binding and receptor activation mechanisms that are
      similar to the binding and activation mechanisms known for other GPCRs.

PMID- 30237174
TI  - Porin proteins have critical functions in mitochondrial phospholipid metabolism
      in yeast.
AB  - Mitochondrial synthesis of cardiolipin (CL) and phosphatidylethanolamine requires
      the transport of their precursors, phosphatidic acid and phosphatidylserine,
      respectively, to the mitochondrial inner membrane. In yeast, the Ups1-Mdm35 and
      Ups2-Mdm35 complexes transfer phosphatidic acid and phosphatidylserine,
      respectively, between the mitochondrial outer and inner membranes. Moreover, a
      Ups1-independent CL accumulation pathway requires several mitochondrial proteins
      with unknown functions including Mdm31. Here, we identified a mitochondrial
      porin, Por1, as a protein that interacts with both Mdm31 and Mdm35 in budding
      yeast (Saccharomyces cerevisiae). Depletion of the porins Por1 and Por2
      destabilized Ups1 and Ups2, decreased CL levels by ~90%, and caused loss of Ups2
      dependent phosphatidylethanolamine synthesis, but did not affect Ups2-independent
      phosphatidylethanolamine synthesis in mitochondria. Por1 mutations that affected
      its interactions with Mdm31 and Mdm35, but not respiratory growth, also decreased
      CL levels. Using HeLa cells, we show that mammalian porins also function in
      mitochondrial CL metabolism. We conclude that yeast porins have specific and
      critical functions in mitochondrial phospholipid metabolism and that porin
      mediated regulation of CL metabolism appears to be evolutionarily conserved.

PMID- 30237176
TI  - Alternatives to specific uric acid lowering treatment in gout in patients with
      cardiovascular disease.

PMID- 30237175
TI  - Quaternary structure of the small amino acid transporter OprG from Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic human pathogen that causes nosocomial
      infections. The P. aeruginosa outer membrane contains specific porins that enable
      substrate uptake, with the outer membrane protein OprG facilitating transport of
      small, uncharged amino acids. However, the pore size of an eight-stranded beta
      barrel monomer of OprG is too narrow to accommodate even the smallest transported
      amino acid, glycine, raising the question of how OprG facilitates amino acid
      uptake. Pro-92 of OprG is critically important for amino acid transport, with a
      P92A substitution inhibiting transport and the NMR structure of this variant
      revealing that this substitution produces structural changes in the barrel rim
      and restricts loop motions. OprG may assemble into oligomers in the outer
      membrane (OM) whose subunit interfaces could form a transport channel. Here, we
      explored the contributions of the oligomeric state and the extracellular loops to
      OprG's function. Using chemical cross-linking to determine the oligomeric
      structures of both WT and P92A OprG in native outer membranes and atomic force
      microscopy, and single-molecule fluorescence of the purified proteins
      reconstituted into lipid bilayers, we found that both protein variants form
      oligomers, supporting the notion that subunit interfaces in the oligomer could
      provide a pathway for amino acid transport. Furthermore, performing transport
      assays with loop-deleted OprG variants, we found that these variants also can
      transport small amino acids, indicating that the loops are not solely responsible
      for substrate transport. We propose that OprG functions as an oligomer and that
      conformational changes in the barrel-loop region might be crucial for its
      activity.

PMID- 30237177
TI  - 'These are not normal times'.

PMID- 30237178
TI  - Defra is 'running out of time' for Brexit plans.

PMID- 30237180
TI  - Vets left in the dark with recruitment campaign.

PMID- 30237181
TI  - Is there a future for 'specials' in equine practice?

PMID- 30237182
TI  - Badger cull authorised in TB low-risk area.

PMID- 30237183
TI  - BVA announces its photography winners.
AB  - Georgina Mills reports on the winning images of the BVA's third annual
      photography competition.

PMID- 30237188
TI  - Warm weather contributes to ectoparasite infestations in backyard chickens.

PMID- 30237189
TI  - Tunnel rehab: surgery for lumbosacral foraminal stenosis in dogs.

PMID- 30237191
TI  - Correction: Spreading of bovine TB by hunting hounds.

PMID- 30237192
TI  - Mycobacterium bovis infection in working foxhounds.

PMID- 30237194
TI  - Maxwell Knight - 'the spy who loved nature'.

PMID- 30237193
TI  - Mycobacterium bovis tuberculosis in hunting hounds.

PMID- 30237195
TI  - 'It's oxymoronic for vets to be activist vegans'.
AB  - Neil Howie argues that livestock farming is essential to meet the global demand
      for food and that vets should be focusing on improving the food-animal cycle
      rather than abolishing it.

PMID- 30237197
TI  - Getting the most out of your time.

PMID- 30237201
TI  - Risk of premature death from chronic conditions higher in UK than many other rich
      countries.

PMID- 30237200
TI  - Targeted analysis of lysosomal directed proteins and their sites of mannose-6
      phosphate modification.
AB  - Mannose-6-phosphate (M6P) is a distinctive post-translational modification
      critical for trafficking of lysosomal acid hydrolases into the lysosome. Improper
      trafficking into the lysosome, and/or lack of certain hydrolases, results in a
      toxic accumulation of their substrates within the lysosomes. To gain insight into
      the enzymes destined to the lysosome these glycoproteins can be distinctively
      enriched and studied using their unique M6P tag. Here we demonstrate, by adapting
      a protocol optimized for the enrichment of phosphopeptides using Fe3+-IMAC
      chromatography, that proteome-wide M6P glycopeptides can be selectively enriched
      and subsequently analyzed by mass spectrometry, taking advantage of exclusive
      phosphomannose oxonium fragment marker ions. As proof-of-concept of this
      protocol, applying it to HeLa cells, we identified hundreds of M6P-modified
      glycopeptides on 35 M6P-modified glycoproteins. We next targeted CHO cells,
      either wild-type or cells deficient in Acp2 and Acp5, which are acid phosphatases
      targeting M6P. In the KO CHO cells we observed a 20-fold increase of the
      abundance of the M6P-modification on endogenous CHO glycoproteins but also on the
      recombinantly over-expressed lysosomal human alpha-galactosidase. We conclude
      that our approach could thus be of general interest for characterization of M6P
      glycoproteomes as well as characterization of lysosomal enzymes used as treatment
      in enzyme replacement therapies targeting lysosomal storage diseases.

PMID- 30237202
TI  - Survey of UK doctors highlights blame culture within the NHS.

PMID- 30237203
TI  - Can disease activity in patients with psoriatic arthritis be adequately assessed
      by a modified Disease Activity index for PSoriatic Arthritis (DAPSA) based on 28
      joints?
AB  - OBJECTIVE: To test the psychometric performance of a modified Disease Activity
      index for PSoriatic Arthritis (DAPSA) using 28 instead of 66 swollen/68 tender
      joint counts (SJC/TJC). METHODS: We included patients with psoriatic arthritis
      (PsA) from the Danish national quality registry DANBIO, divided into examination
      (n=3157 patients, 23987 visits) and validation cohorts (n=3154 patients, 24160
      visits). We defined DAPSA28 = (28TJC * conversion factor1) + (28SJC * conversion
      factor2) + patient global (0-10VAS) + pain (0-10VAS) + C reactive protein (CRP)
      (mg/dL). Identification of the conversion factors was performed by generalised
      estimating equations in the examination cohort and evaluation of criterion,
      correlational and construct validity in the validation cohort. RESULTS: We
      estimated DAPSA28 = (28TJC * 1.6) + (28SJC * 1.6) + patient global (0-10VAS) +
      pain (0-10VAS) + CRP (mg/dL). Criterion validity: DAPSA/DAPSA28 had comparable
      discriminative power expressed as standardised mean difference (DAPSA, 0.90;
      DAPSA28, 0.93) to distinguish between patients in high and low disease activity.
      Kappa with quadratic weighting of DAPSA/DAPSA28 disease activity states was high:
      0.92 (95% CI 0.92 to 0.92). Standardised response means for DAPSA/DAPSA28 were 
      0.96/-0.92 for visits after biological DMARD-initiation. Correlational validity:
      Baseline DAPSA/DAPSA28 had high correlation with 28-joint disease activity score
      with CRP (r=0.87/r=0.93), simplified disease activity index (r=0.92/r=0.99),
      p<0.001. Bland-Altman plot showed better agreement between DAPSA/DAPSA28 for low
      than high disease activity. Construct validity: DAPSA/DAPSA28 were similarly
      correlated to Health Assessment Questionnaire; r=0.60/0.62, p<0.001.
      DAPSA/DAPSA28 discriminated patients reporting their symptom state as acceptable
      versus not acceptable equally well: mean (SD) 9.1 (8.7)/8.4 (8.0) and 24.2
      (14.9)/22.5 (13.8), respectively. CONCLUSION: Our study suggests that data sets
      with only 28-joint counts available can be used to calculate DAPSA28, especially
      in patients with low disease activity. DAPSA28 showed good criterion,
      correlational and construct validity and sensitivity to change. Still, our
      results support that 66/68 joint count should be performed and the original DAPSA
      should be preferred in PsA.

PMID- 30237205
TI  - Non-Enzymatic Synthesis of Bioactive Isoprostanoids in the Diatom Phaeodactylum
      following Oxidative Stress.
AB  - The ecological success of diatoms requires a remarkable ability to survive many
      types of stress, including variations in temperature, light, salinity, and
      nutrient availability. On exposure to these stresses, diatoms exhibit common
      responses, including growth arrest, impairment of photosynthesis, production of
      reactive oxygen species, and accumulation of triacylglycerol (TAG). We studied
      the production of cyclopentane oxylipins derived from fatty acids in the diatom
      Phaeodactylum tricornutum in response to oxidative stress. P. tricornutum lacks
      the enzymatic pathway for producing cyclopentane-oxylipins, such as jasmonate,
      prostaglandins, or thromboxanes. In cells subjected to increasing doses of
      hydrogen peroxide (H2O2), we detected nonenzymatic production of isoprostanoids,
      including six phytoprostanes, three F2t-isoprostanes, two F3t-isoprostanes, and
      three F4t-neuroprostanes, by radical peroxidation of alpha-linolenic,
      arachidonic, eicosapentaenoic, and docosahexanoic acids, respectively. H2O2 also
      triggered photosynthesis impairment and TAG accumulation. F1t-phytoprostanes
      constitute the major class detected (300 pmol per 1 million cells; intracellular
      concentration, ~4 um). Only two glycerolipids, phosphatidylcholine and
      diacylglycerylhydroxymethyl-trimethyl-alanine, could provide all substrates for
      these isoprostanoids. Treatment of P. tricornutum with nine synthetic
      isoprostanoids produced an effect in the micromolar range, marked by the
      accumulation of TAG and reduced growth, without affecting photosynthesis.
      Therefore, the emission of H2O2 and free radicals upon exposure to stresses can
      lead to glycerolipid peroxidation and nonenzymatic synthesis of isoprostanoids,
      inhibiting growth and contributing to the induction of TAG accumulation via
      unknown processes. This characterization of nonenzymatic oxylipins in P.
      tricornutum opens a field of research on the study of processes controlled by
      isoprostanoid signaling in various physiological and environmental contexts in
      diatoms.

PMID- 30237206
TI  - An in Vivo Imaging Assay Detects Spatial Variability in Glucose Release from
      Plant Roots.
AB  - Plants secrete a plethora of metabolites into the rhizosphere that allow them to
      obtain nutrients necessary for growth and modify microbial communities around the
      roots. Plants release considerable amounts of photosynthetically fixed carbon
      into the rhizosphere; hence, it is important to understand how carbon moves from
      the roots into the rhizosphere. Approaches used previously to address this
      question involved radioactive tracers, fluorescent probes, and biosensors to
      study sugar movement in the roots and into the rhizosphere. Although quite
      effective for studying sugar movement, it has been challenging to obtain data on
      spatial and temporal variability in sugar exudation using these techniques. In
      this study, we developed a gel-based enzyme-coupled colorimetric and fluorometric
      assay to image glucose (Glc) in vivo and used this assay to show that there is
      spatial variability in Glc release from plant roots. We found that the primary
      roots of maize (Zea mays) released more Glc from the base of the root than from
      the root tip and that the Glc release rate is reduced in response to water
      stress. These findings were confirmed independently by quantifying Glc release in
      well-watered and water-stressed maize primary roots using high-performance anion
      exchange chromatography. Additionally, we demonstrated differential patterns of
      Glc exudation in different monocot and eudicot plant species. These findings and
      their implications on root-rhizosphere interactions are discussed.

PMID- 30237204
TI  - Halophytism: What Have We Learnt From Arabidopsis thaliana Relative Model
      Systems?
AB  - Halophytes are able to thrive in salt concentrations that would kill 99% of other
      plant species, and identifying their salt-adaptive mechanisms has great potential
      for improving the tolerance of crop plants to salinized soils. Much research has
      focused on the physiological basis of halophyte salt tolerance, whereas the
      elucidation of molecular mechanisms has traditionally lagged behind due to the
      absence of a model halophyte system. However, over the last decade and a half,
      two Arabidopsis (Arabidopsis thaliana) relatives, Eutrema salsugineum and
      Schrenkiella parvula, have been established as transformation-competent models
      with various genetic resources including high-quality genome assemblies. These
      models have facilitated powerful comparative analyses with salt-sensitive
      Arabidopsis to unravel the genetic adaptations that enable a halophytic
      lifestyle. The aim of this review is to explore what has been learned about
      halophytism using E. salsugineum and S. parvula We consider evidence from
      physiological and molecular studies suggesting that differences in salt tolerance
      between related halophytes and salt-sensitive plants are associated with
      alterations in the regulation of basic physiological, biochemical, and molecular
      processes. Furthermore, we discuss how salt tolerance mechanisms of the
      halophytic models are reflected at the level of their genomes, where evolutionary
      processes such as subfunctionalization and/or neofunctionalization have altered
      the expression and/or functions of genes to facilitate adaptation to saline
      conditions. Lastly, we summarize the many areas of research still to be addressed
      with E. salsugineum and S. parvula as well as obstacles hindering further
      progress in understanding halophytism.

PMID- 30237207
TI  - Differential Roles of the Thylakoid Lumenal Deg Protease Homologs in Chloroplast
      Proteostasis.
AB  - Deg proteases are involved in protein quality control in prokaryotes. Of the
      three Arabidopsis (Arabidopsis thaliana) homologs, Deg1, Deg5, and Deg8, located
      in the thylakoid lumen, Deg1 forms a homohexamer, whereas Deg5 and Deg8 form a
      heterocomplex. Both Deg1 and Deg5-Deg8 were shown separately to degrade
      photosynthetic proteins during photoinhibition. To investigate whether Deg1 and
      Deg5-Deg8 are redundant, a full set of Arabidopsis Deg knockout mutants were
      generated and their phenotypes were compared. Under all conditions tested, deg1
      mutants were affected more than the wild type and deg5 and deg8 mutants.
      Moreover, overexpression of Deg5-Deg8 could only partially compensate for the
      loss of Deg1. Comparative proteomics of deg1 mutants revealed moderate up
      regulation of thylakoid proteins involved in photoprotection, assembly, repair,
      and housekeeping and down-regulation of those that form photosynthetic complexes.
      Quantification of protein levels in the wild type revealed that Deg1 was 2-fold
      more abundant than Deg5-Deg8. Moreover, recombinant Deg1 displayed higher in
      vitro proteolytic activity. Affinity enrichment assays revealed that Deg1 was
      precipitated with very few interacting proteins, whereas Deg5-Deg8 was associated
      with a number of thylakoid proteins, including D1, OECs, LHCBs, Cyt b 6 f, and
      NDH subunits, thus implying that Deg5-Deg8 is capable of binding substrates but
      is unable to degrade them efficiently. This work suggests that differences in
      protein abundance and proteolytic activity underlie the differential importance
      of Deg1 and Deg5-Deg8 protease complexes observed in vivo.

PMID- 30237208
TI  - Evidence for the Regulation of Gynoecium Morphogenesis by ETTIN via Cell Wall
      Dynamics.
AB  - ETTIN (ETT) is an atypical member of the AUXIN RESPONSE FACTOR family of
      transcription factors that plays a crucial role in tissue patterning in the
      Arabidopsis (Arabidopsis thaliana) gynoecium. Though recent insights have
      provided valuable information on ETT's interactions with other components of
      auxin signaling, the biophysical mechanisms linking ETT to its ultimate effects
      on gynoecium morphology were until now unknown. Here, using techniques to assess
      cell-wall dynamics during gynoecium growth and development, we provide a coherent
      body of evidence to support a model in which ETT controls the elongation of the
      valve tissues of the gynoecium through the positive regulation of pectin
      methylesterase (PME) activity in the cell wall. This increase in PME activity
      results in an increase in the level of demethylesterified pectins and a
      consequent reduction in cell wall stiffness, leading to elongation of the valves.
      Though similar biophysical mechanisms have been shown to act in the stem apical
      meristem, leading to the expansion of organ primordia, our findings demonstrate
      that regulation of cell wall stiffness through the covalent modification of
      pectin also contributes to tissue patterning within a developing plant organ.

PMID- 30237210
TI  - A Proof-of-Concept Study to Inhibit ABCG2- and ABCB1-Mediated Efflux Transport at
      the Human Blood-Brain Barrier.
AB  - ABCB1 and ABCG2 are two efflux transporters at the blood-brain barrier (BBB)
      which effectively restrict brain distribution of dual ABCB1/ABCG2 substrate
      drugs, such as tyrosine kinase inhibitors. Pharmacological inhibition of
      ABCB1/ABCG2 may improve the efficacy of dual substrate drugs for treatment of
      brain tumors, but no marketed ABCB1/ABCG2 inhibitors are currently available. In
      the present study, we examined the potential of supratherapeutic-dose oral
      erlotinib to inhibit ABCB1/ABCG2 activity at the human BBB. Methods: Healthy male
      subjects underwent two consecutive PET scans with 11C-erlotinib; a baseline scan
      and a second scan either with concurrent i.v. infusion of the ABCB1 inhibitor
      tariquidar (3.75 mg/min, n = 5) or after oral intake of single ascending doses of
      erlotinib (300 mg: n = 7, 650 mg: n = 8 or 1,000 mg: n = 2). Results: While
      tariquidar administration had no effect on 11C-erlotinib brain distribution, oral
      erlotinib led, at the 650 mg dose, to significant increases in volume of
      distribution (VT, +23+/-13%, P = 0.008), influx rate constant of radioactivity
      from plasma into brain (K1, +58+/-26%, P = 0.008) and brain area under the time
      activity curve (AUCbrain, +78+/-17%, P = 0.008), presumably due to combined
      partial saturation of ABCG2 and ABCB1 activity. Inclusion of further subjects
      into the 1,000 mg dose group was precluded by adverse skin events (rash).
      Conclusion: Supratherapeutic-dose erlotinib may be used to enhance brain delivery
      of ABCB1/ABCG2 substrate anticancer drugs, but its clinical applicability for
      continuous ABCB1/ABCG2 inhibition at the BBB may be limited by safety concerns.

PMID- 30237211
TI  - 18F-FDG PET/CT for Systemic Staging of Newly Diagnosed Breast Cancer in Men.
AB  - 18F-FDG PET/CT has demonstrated substantial value in systemic staging of newly
      diagnosed breast cancer in women. However, it is not known whether breast cancer
      in male patients benefit similarly. This study assesses 18F-FDG PET/CT systemic
      staging in patients with newly diagnosed male breast cancer and determines
      detection rates for unsuspected distant metastases stratified by pre-PET/CT
      stage. Methods: In this Institutional Review Board-approved retrospective study,
      our Healthcare Information System was screened for stage I-III male patients with
      breast cancer who underwent 18F-FDG PET/CT prior to systemic or radiation therapy
      from 2004 to 2017. Initial stage was determined by mammography, ultrasound,
      and/or surgery. 18F-FDG PET/CT was evaluated to identify unsuspected extra
      axillary regional nodal and distant metastases, and a Post PET/CT stage was
      determined. Rates of upstaging to stage IV were determined for each initial
      stage. Results: During the 14-year period, 10,124 unique patients underwent 18F
      FDG PET/CT for breast cancer at our institution. Of these, 106 patients were
      male, and 39 of these patients were imaged at initial staging and met the
      inclusion criteria. Median age was 62 years (range: 31-90), most had ductal
      carcinoma (95%), and most were ER+ (97%). In 7 of 39 patients (18%), 18F-FDG
      PET/CT identified previously unsuspected distant metastases, which increased
      patient stage to IV. This included 3 of 19 (16%) initial stage IIB patients and 4
      of 12 (33%) initial stage III patients. 18F-FDG PET/CT also detected an
      unsuspected synchronous lymphoma in one patient. Conclusion:18F-FDG PET/CT
      revealed previously unsuspected distant metastases in 16% of male patients with
      pre-PET/CT stage IIB breast cancer and 33% of those with stage III breast cancer.
      These rates are comparable to previously published upstaging rates in female
      patients. 18F-FDG PET/CT demonstrates value for systemic staging of male patients
      with breast cancer, and should be considered for use in newly diagnosed patients,
      particularly those with stage IIB and III disease.

PMID- 30237212
TI  - Evaluation of 111In-DOTA-5D3, a Surrogate SPECT Imaging Agent for
      Radioimmunotherapy of Prostate-Specific Membrane Antigen.
AB  - BACKGROUND: 5D3 is a new high-affinity murine monoclonal antibody specific for
      prostate-specific membrane antigen (PSMA). PSMA is a target for the imaging and
      therapy of prostate cancer. 111In-Labeled antibodies have been used as surrogates
      for 177Lu/90Y-labeled therapeutics. We characterized 111In-DOTA-5D3 by SPECT-CT
      imaging, tissue biodistribution studies and dosimetry. METHODS: Radiolabeling,
      stability, cell uptake, and internalization of 111In-DOTA-5D3 were performed by
      established techniques. Biodistribution and SPECT imaging were done in male non
      obese diabetic/severe combined immunodeficient (NOD/SCID) mice bearing human
      PSMA(+) PC3 PIP and PSMA(-) PC3 flu prostate cancer xenografts on the upper right
      and left flanks, respectively at 2, 24, 48, 72 and 192 h post-injection.
      Biodistribution was also evaluated in tumor-free, healthy male CD-1 mice.
      Blocking studies were performed by co-injection of 10-fold and 50-fold excess of
      5D3 followed by biodistribution at 24 h to determine PSMA binding specificity.
      The radiation absorbed doses were calculated based murine biodistribution data,
      which were translated to a human adult male using organ weights from the
      software, OLINDA/EXM. RESULTS:111In-DOTA-5D3 was synthesized with specific
      radioactivity ~3.92 +/- 0.75 MBq/ug (105.90 +/- 20.40 uCi/ug of mAb).
      Distribution of 111In-DOTA-5D3 in PSMA(+) PC3 PIP tumor peaked at 24 h post
      injection and remained high until 72 h. Uptake in normal tissues including the
      blood, spleen, liver, heart, and lungs was highest at 2 h post-injection. Co
      injection of 111In-DOTA-5D3 with 10- and 50-fold excess of non-radiolabeled
      antibody significantly reduced PSMA(+) PC3 PIP tumor and salivary gland uptake at
      24 h, but did not reduce uptake to kidneys and lacrimal glands. Significant
      clearance of 111In-DOTA-5D3 from all organs occurred at 192 h. The highest
      radiation dose was received by the liver with 0.5 mGy per MBq followed by spleen
      and kidneys. Radiation absorbed doses of salivary and lacrimal glands and bone
      marrow were low. CONCLUSION:111In-DOTA-5D3 is a new radiolabeled antibody for
      imaging and a surrogate for therapy of malignant tissues expressing PSMA.

PMID- 30237213
TI  - Production of 15O for medical applications via the 16O(gamma,n)15O reaction.
AB  - Oxygen-15 (t1/2 = 122 s) is a useful radionuclide for Positron Emission
      Tomography (PET) applications. Current production of 15O typically makes use of
      the 14N(d,n)15O, 15N(p,n)15O or 16O(p,pn)15O reactions using an accelerator. A
      novel approach for the production of 15O is via the 16O(gamma,n)15O reaction
      using an electron linear accelerator (eLINAC). Photonuclear reactions using an
      eLINAC may allow for feasible and economical production of 15O compared to the
      current methods. Methods: In this work, experiments using a repurposed Clinac
      were conducted using oxygen-containing alumina as a target material to study the
      production rate of 15O. Additional studies were conducted using a water target
      cell. Simulations using Geant4 were conducted to predict the activity and power
      dissipation in the target. Results: Bremsstrahlung radiation from the electron
      beam, and consequently 15O production via photonuclear reactions, is enhanced
      when a high Z material, tungsten, is placed in front of the target. The alumina
      irradiations provided preliminary data to optimize the beam parameters and target
      configuration. The optimal thickness of tungsten was 1.4 mm for both the
      simulated and measured studies of alumina. Simulations of irradiated water
      targets showed that tungsten thicker than 1.4 mm resulted in less photons
      available to activate the water, thus a higher current was required to achieve a
      fixed dose. Alternatively, for a constant tungsten thickness, more power is
      deposited in the target with increasing beam energy requiring a lower current to
      achieve a fixed dose. Actual irradiations of a water target yield a quantity of
      15O in the water that was consistent with expectations based on irradiations of
      Alumina. Conclusion: Several parameters should be considered regarding the
      photonuclear production of 15O for an average patient dose of 1850 MBq (50 mCi)
      in 10 mL. This work illustrates a variety of machine parameters which are capable
      of achieving a reasonable patient dose. Our simulations show that the power
      deposited in the target for these parameters is less than commercially operated
      cyclotron targets for the production of 18F. Thus, this work demonstrates that
      the photonuclear production of 15O may be a new production path for this useful
      radionuclide.

PMID- 30237209
TI  - Transcription Promotes the Interaction of the FAcilitates Chromatin Transactions
      (FACT) Complex with Nucleosomes in Saccharomyces cerevisiae.
AB  - The FACT (FAcilitates Chromatin Transactions) complex is a conserved complex that
      maintains chromatin structure on transcriptionally active genes. Consistent with
      this, FACT is enriched on highly expressed genes, but how it is targeted to these
      regions is unknown. In vitro, FACT binds destabilized nucleosomes, supporting the
      hypothesis that FACT is targeted to transcribed chromatin through recognition of
      RNA polymerase (RNAP)-disrupted nucleosomes. In this study, we used high
      resolution analysis of FACT occupancy in Saccharomyces cerevisiae to test this
      hypothesis. We demonstrate that FACT interacts with nucleosomes in vivo and that
      its interaction with chromatin is dependent on transcription by any of the three
      RNAPs. Deep sequencing of micrococcal nuclease-resistant fragments shows that
      FACT-bound nucleosomes exhibit differing nuclease sensitivity compared to bulk
      chromatin, consistent with a modified nucleosome structure being the preferred
      ligand for this complex. Interestingly, a subset of FACT-bound nucleosomes may be
      "overlapping dinucleosomes," in which one histone octamer invades the ~147-bp
      territory normally occupied by the adjacent nucleosome. While the differing
      nuclease sensitivity of FACT-bound nucleosomes could also be explained by the
      demonstrated ability of FACT to alter nucleosome structure, transcription
      inhibition restores nuclease resistance, suggesting that it is not due to FACT
      interaction alone. Collectively, these results are consistent with a model in
      which FACT is targeted to transcribed genes through preferential interaction with
      RNAP-disrupted nucleosomes.

PMID- 30237214
TI  - Synthesis and preclinical characterization of the PSMA-targeted hybrid tracer
      PSMA-I&F for nuclear and fluorescence imaging of prostate cancer.
AB  - The PSMA-targeted radiotracers 68Ga/177Lu-PSMA-I&T and 99mTc-PSMA-I&S are
      currently successfully employed for clinical PET imaging, radionuclide therapy
      and radioguided surgery of metastatic prostate cancer. To additionally exploit
      the high sensitivity and spatial resolution of fluorescence imaging for improved
      surgical guidance, a first PSMA-I&T-based hybrid tracer, PSMA-I&F (DOTAGA-k(Sulfo
      Cy5)-y-nal-k-Sub-KuE), has been developed and evaluated. The in vitro PSMA
      targeting efficiency of PSMA-I&F, the reference PSMA-I&T and their corresponding
      natGa-/68Ga- and natLu/177Lu-counterparts was determined in LNCaP cells via
      competitive binding assays (IC50), dual-tracer radioligand- and fluorescence
      internalization studies. Biodistribution and small-animal PET imaging studies
      were performed in CB17-SCID and LNCaP xenograft bearing SHO mice, respectively,
      and complemented by intraoperative far-red fluorescence imaging using a clinical
      laparoscope. Additionally, fully automated serial cryosectioning and fluorescence
      imaging of one tumor-bearing animal as well as PSMA immunohistochemistry (IHC)
      and fluorescence microscopy of organ cryosections (tumor, kidney, spleen) were
      also performed. Compared to the parent PSMA-I&T analogs, the PSMA-affinities of
      PSMA-I&F and its natGa-/natLu-complexes remained high and unaffected by dye
      conjugation (7.9<IC50<10.5 nM for all ligands). The same was observed for the
      internalization of 68Ga- and 177Lu-PSMA-I&F. In vivo, blood clearance of 68Ga-
      and 177Lu-PSMA-I&F was only slightly delayed by high plasma protein binding (94
      95%), and very low accumulation in non-target organs was observed already at 1h
      p.i.. Dynamic PET imaging confirmed PSMA-specific (as demonstrated by coinjection
      of 2-PMPA) uptake into the LNCaP xenograft (4.5+/-1.8%iD/g) and the kidneys
      (106+/-23%iD/g). Tumor/background ratios of 2.1, 5.2, 9.6 and 9.6 for blood,
      liver, intestines and muscle, respectively, at 1h p.i. led to excellent imaging
      contrast in 68Ga-PSMA-I&F PET and in intraoperative fluorescence imaging.
      Furthermore, fluorescence imaging of tissue cryosections allowed high-resolution
      visualization of intraorgan PSMA-I&F distribution in vivo and its correlation
      with PSMA expression as determined by IHC. Thus, with its high PSMA-targeting
      efficiency and favorable pharmacokinetic profile, 68Ga/177Lu-PSMA-I&F serves as
      an excellent proof-of-concept compound for the general feasibility of PSMA-I&T
      based hybrid imaging. The PSMA-I&T scaffold represents a versatile PSMA-targeted
      lead structure, allowing relatively straightforward adaptation to the different
      structural requirements of dedicated nuclear or hybrid imaging agents.

PMID- 30237215
TI  - The Relationship between Intradialytic Hypotension and Hospitalized Mesenteric
      Ischemia: A Case-Control Study.
AB  - BACKGROUND AND OBJECTIVES: Mesenteric ischemia is a rare but devastating
      condition caused by insufficient blood supply to meet the demands of intestinal
      metabolism. In patients with ESKD, it can be difficult to diagnose and has a >70%
      mortality rate. Patients on hemodialysis have a high prevalence of predisposing
      conditions for mesenteric ischemia, but the contribution of intradialytic
      hypotension, a potential modifiable risk factor, has not been well described.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used data from the US Renal
      Data System to identify 626 patients on hemodialysis with a hospitalized
      mesenteric ischemia event (cases). We selected 2428 controls in up to a 1:4 ratio
      matched by age, sex, black race, incident dialysis year, diabetes mellitus,
      coronary artery disease, and peripheral artery disease. We used six different
      definitions of intradialytic hypotension on the basis of prior studies, and
      categorized patients as having had intradialytic hypotension if >=30% of
      hemodialysis sessions in the 30 days before the event met the specified
      definition. RESULTS: The proportion of patients with intradialytic hypotension
      varied depending on its definition: from 19% to 92% of cases and 11% to 94% of
      controls. Cases had a higher adjusted odds (1.82; 95% confidence interval, 1.47
      to 2.26) of having had intradialytic hypotension in the preceding 30 days than
      controls when using nadir-based intradialytic hypotension definitions such as
      nadir systolic BP <90 mm Hg. To examine a potential dose-response association of
      intradialytic hypotension with hospitalized mesenteric ischemia, we categorized
      patients by the proportion of hemodialysis sessions having intradialytic
      hypotension, defined using the Nadir90 definition (0%, 1%-9%, 10%-29%, 30%-49%,
      and >=50%), and found a direct association of proportion of intradialytic
      hypotension with hospitalized mesenteric ischemia (P-trend<0.001). CONCLUSIONS:
      Patients with hospitalized mesenteric ischemia had significantly higher odds of
      having had intradialytic hypotension in the preceding 30 days than controls, as
      defined by nadir-based definitions.

PMID- 30237217
TI  - Beware Intradialytic Hypotension: How Low Is Too Low?

PMID- 30237218
TI  - Metabolic Acidosis and Cardiovascular Disease Risk in CKD.

PMID- 30237216
TI  - Recovery of Kidney Function in Children Treated with Maintenance Dialysis.
AB  - BACKGROUND AND OBJECTIVES: Data on recovery of kidney function in pediatric
      patients with presumed ESKD are scarce. We examined the occurrence of recovery of
      kidney function and its determinants in a large cohort of pediatric patients on
      maintenance dialysis in Europe. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Data for 6574 patients from 36 European countries commencing dialysis at an age
      below 15 years, between 1990 and 2014 were extracted from the European Society
      for Pediatric Nephrology/European Renal Association-European Dialysis and
      Transplant Association Registry. Recovery of kidney function was defined as
      discontinuation of dialysis for at least 30 days. Time to recovery was studied
      using a cumulative incidence competing risk approach and adjusted Cox
      proportional hazard models. RESULTS: Two years after dialysis initiation, 130
      patients (2%) experienced recovery of their kidney function after a median of 5.0
      (interquartile range, 2.0-9.6) months on dialysis. Compared with patients with
      congenital anomalies of the kidney and urinary tract, recovery more often
      occurred in patients with vasculitis (11% at 2 years; adjusted hazard ratio [HR],
      20.4; 95% confidence interval [95% CI], 9.7 to 42.8), ischemic kidney failure
      (12%; adjusted HR, 11.4; 95% CI, 5.6 to 23.1), and hemolytic uremic syndrome
      (13%; adjusted HR, 15.6; 95% CI, 8.9 to 27.3). Younger age and initiation on
      hemodialysis instead of peritoneal dialysis were also associated with recovery.
      For 42 patients (32%), recovery was transient as they returned to kidney
      replacement therapy after a median recovery period of 19.7 (interquartile range,
      9.0-41.3) months. CONCLUSIONS: We demonstrate a recovery rate of 2% within 2
      years after dialysis initiation in a large cohort of pediatric patients on
      maintenance dialysis. There is a clinically important chance of recovery in
      patients on dialysis with vasculitis, ischemic kidney failure, and hemolytic
      uremic syndrome, which should be considered when planning kidney transplantation
      in these children.

PMID- 30237220
TI  - A synthetic promoter for multi-stage expression to probe complementary functions
      of Plasmodium adhesins.
AB  - Gene expression of malaria parasites is mediated by the apicomplexan Apetala2
      (ApiAP2) transcription factor family. Different ApiAP2s control gene expression
      at distinct stages in the complex life cycle of the parasite, ensuring timely
      expression of stage-specific genes. ApiAP2s recognize short cis-regulatory
      elements that are enriched in the upstream/promoter region of their target genes.
      This should, in principle, allow the generation of 'synthetic' promoters that
      drive gene expression at desired stages of the Plasmodium life cycle. Here we
      test this concept by combining cis-regulatory elements of two genes expressed
      successively within the mosquito part of the life cycle. Our tailored 'synthetic'
      promoters, named Spooki 1.0 and Spooki 2.0, activate gene expression in early and
      late mosquito stages, as shown by the expression of a fluorescent reporter. We
      used these promoters to address the specific functionality of two related
      adhesins that are exclusively expressed either during the early or late mosquito
      stage. By modifying the expression profile of both adhesins in absence of their
      counterpart we were able to test for complementary functions in gliding and
      invasion. We discuss the possible advantages and drawbacks of our approach.This
      article has an associated First Person interview with the first author of the
      paper.

PMID- 30237219
TI  - Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in
      Patients with CKD: A Pilot Randomized Cross-Over Study.
AB  - BACKGROUND AND OBJECTIVES: We examined the effect of alkali replacement for
      metabolic acidosis on vascular endothelial function in patients with CKD.
      METHODS: We performed a pilot, prospective, open-label 14-week crossover study
      examining the effect of oral sodium bicarbonate treatment on vascular function in
      20 patients with an eGFR of 15-44 ml/min per 1.73 m2 with low serum bicarbonate
      levels (16-21 mEq/L). Each period was 6 weeks in duration with a 2-week washout
      period in between. Patients were treated to goal serum bicarbonate of >=23 mEq/L.
      The primary end point was change in brachial artery flow-mediated dilation (FMD)
      between treatment and control conditions. Secondary end points included changes
      in markers of inflammation, bone turnover, mineral metabolism, and calcification.
      RESULTS: Eighteen patients completed the study and were included in the primary
      efficacy analysis. The mean (SD) age and eGFR were 59 (12) years and 26 (8)
      ml/min per 1.73 m2, respectively. Serum bicarbonate increased significantly with
      sodium bicarbonate treatment (+2.7+/-2.9 mEq/L, P<=0.001), whereas there was no
      change in bicarbonate levels in the control group. FMD significantly improved
      after sodium bicarbonate therapy (mean+/-SD, FMD baseline: 4.1%+/-4.1%; 6 weeks:
      5.2%+/-2.9%; P=0.04) There was no significant change in FMD in the control group
      (mean+/-SD, FMD baseline: 4.6%+/-3.1%; 6 weeks: 4.1%+/-3.4%; P=0.20). Compared
      with control, sodium bicarbonate treatment resulted in a significant increase in
      FMD (mean, 1.8%; 95% confidence interval, 0.3 to 3.3; P=0.02). There was no
      significant change in bone markers or serum calcification propensity with
      treatment. Serum phosphorus and intact fibroblast growth factor 23 increased
      significantly during treatment. CONCLUSIONS: Treatment of metabolic acidosis with
      sodium bicarbonate significantly improved vascular endothelial function in
      patients with stages 3b and 4 CKD.

PMID- 30237222
TI  - PLK4 is a microtubule-associated protein that self-assembles promoting de novo
      MTOC formation.
AB  - The centrosome is an important microtubule-organising centre (MTOC) in animal
      cells. It consists of two barrel-shaped structures, the centrioles, surrounded by
      the pericentriolar material (PCM), which nucleates microtubules. Centrosomes can
      form close to an existing structure (canonical duplication) or de novo How
      centrosomes form de novo is not known. The master driver of centrosome
      biogenesis, PLK4, is critical for the recruitment of several centriole
      components. Here, we investigate the beginning of centrosome biogenesis, taking
      advantage of Xenopus egg extracts, where PLK4 can induce de novo MTOC formation (
      Eckerdt et al., 2011; Zitouni et al., 2016). Surprisingly, we observe that in
      vitro, PLK4 can self-assemble into condensates that recruit alpha- and beta
      tubulins. In Xenopus extracts, PLK4 assemblies additionally recruit STIL, a
      substrate of PLK4, and the microtubule nucleator gamma-tubulin, forming
      acentriolar MTOCs de novo The assembly of these robust microtubule asters is
      independent of dynein, similar to what is found for centrosomes. We suggest a new
      mechanism of action for PLK4, where it forms a self-organising catalytic scaffold
      that recruits centriole components, PCM factors and alpha- and beta-tubulins,
      leading to MTOC formation.This article has an associated First Person interview
      with the first author of the paper.

PMID- 30237223
TI  - Activation of mammalian cytoplasmic dynein in multimotor motility assays.
AB  - Long-range intracellular transport is facilitated by motor proteins, such as
      kinesin-1 and cytoplasmic dynein, moving along microtubules (MTs). These motors
      often work in teams for the transport of various intracellular cargos. Although
      transport by multiple kinesin-1 motors has been studied extensively in the past,
      collective effects of cytoplasmic dynein are less well understood. On the level
      of single molecules, mammalian cytoplasmic dynein is not active in the absence of
      dynactin and adaptor proteins. However, when assembled into a team bound to the
      same cargo, processive motility has been observed. The underlying mechanism of
      this activation is not known. Here, we found that in MT gliding motility assays
      the gliding velocity increased with dynein surface density and MT length.
      Developing a mathematical model based on single-molecule parameters, we were able
      to simulate the observed behavior. Integral to our model is the usage of an
      activation term, which describes a mechanical activation of individual dynein
      motors when being stretched by other motors. We hypothesize that this activation
      is similar to the activation of single dynein motors by dynactin and adaptor
      proteins.This article has an associated First Person interview with the first
      author of the paper.

PMID- 30237221
TI  - RPGRIP1L helps to establish the ciliary gate for entry of proteins.
AB  - Mutations in transition zone genes change the composition of the ciliary
      proteome. We isolated new mutations in RPGRIP1L (denotated as RPG1 in algae) that
      affect the localization of the transition zone protein NPHP4 in the model
      organism Chlamydomonas reinhardtii NPHP4 localization is not affected in multiple
      new intraflagellar transport (IFT) mutants. We compared the proteome of cilia
      from wild-type and mutants that affect the transition zone (RPGRIP1L) or IFT
      (IFT172 and DHC1b) by mass spectrometry. The rpg1-1 mutant cilia show the most
      dramatic increase in cytoplasmic proteins. These nonciliary proteins function in
      translation, membrane remodeling, ATP production and as chaperonins. These
      proteins are excluded in isolated cilia from fla11-1 (IFT172) and fla24-1
      (DHC1b). Our data support the idea that RPGRIP1L, but not IFT proteins, acts as
      part of the gate for cytoplasmic proteins. The rpg1-1 cilia lack only a few
      proteins, which suggests that RPGRIP1L only has a minor role of in the retention
      of ciliary proteins. The fla11-1 mutant shows the greatest loss/reduction of
      proteins, and one-third of these proteins have a transmembrane domain. Hence,
      IFT172 may play a role in the retention of proteins.

PMID- 30237225
TI  - Public Health England's sugar reduction programme did not "fail".

PMID- 30237224
TI  - Regulated reconstitution of spindle checkpoint arrest and silencing through
      chemically induced dimerisation in vivo.
AB  - Chemically induced dimerisation (CID) uses small molecules to control specific
      protein-protein interactions. We employed CID dependent on the plant hormone
      abscisic acid (ABA) to reconstitute spindle checkpoint signalling in fission
      yeast. The spindle checkpoint signal usually originates at unattached or
      inappropriately attached kinetochores. These are complex, multiprotein structures
      with several important functions. To bypass kinetochore complexity, we took a
      reductionist approach to studying checkpoint signalling. We generated a synthetic
      checkpoint arrest ectopically by inducing heterodimerisation of the checkpoint
      proteins Mph1 (the fission yeast homologue of Mps1) and Spc7 (the fission yeast
      homologue of KNL1). These proteins were engineered such that they cannot localise
      to kinetochores, and only form a complex in the presence of ABA. Using this novel
      assay we were able to checkpoint arrest a synchronous population of cells within
      30 min of ABA addition. This assay allows detailed genetic dissection of
      checkpoint activation and, importantly, also provides a valuable tool for
      studying checkpoint silencing. To analyse silencing of the checkpoint and the
      ensuing mitotic exit, we simply washed out the ABA from arrested fission yeast
      cells. We show here that silencing is critically dependent on protein phosphatase
      1 (PP1) recruitment to Mph1-Spc7 signalling platforms.

PMID- 30237226
TI  - Apoptosis of cardiomyocytes in diabetic cardiomyopathy involves overexpression of
      glycogen synthase kinase-3beta.
AB  - To evaluate the role of glycogen synthase kinase-3beta (GSK-3beta) in the
      apoptosis of cardiomyocytes in diabetic cardiomyopathy (DCM). Diabetes mellitus
      (DM) in rats were induced by intraperitoneal injection of 1% streptozotocin
      (STZ), and lithium chloride (LiCl) was used to decrease the expression of GSK
      3beta. Hematoxylin/eosin staining (HE) staining and the terminal
      deoxyribonucleotide transferase-mediated dUTP-digoxigenin nick end labeling
      (TUNEL) assay was conducted to evaluate the pathological injury and apoptosis of
      cardiomyocytes respectively. Western blot was applied to detect the protein 
      expressions of Cleaved-caspase 3, caspase 3, Bax and Bcl-2 in rat cardiomyocytes.
      Real-time polymerase chain reaction (RT-PCR) was applied to detect the gene
      expressions of Phosphoinositide 3-kinases (PI3K), Akt, and GSK-3beta in rat
      cardiomyocytes. DM-induced cardiomyocyte injuries, which were presented as
      capillary basement membrane thickening, interstitial fibrosis, cardiomyocyte
      hypertrophy and necrosis in HE staining and increased apoptosis detected by TUNEL
      assay. When comparing with the control group, the mRNA expression of PI3K and Akt
      in DM group obviously decreased but the mRNA expression of GSK-3beta obviously
      elevated ( P <0.05). In addition, the ratio of Cleaved-caspase 3/caspase 3 and
      Bax/Bcl-2 were notably increased in DM group conpared to control group ( P
      <0.05). LiCl, as an inhibitor of GSK-3 apparently reduced the expression of GSK
      3beta mRNA ( P <0.05) but not the PI3K and Akt comparing with the DM group. LiCl
      also attenuated the myocardial injury and apoptosis induced by DM. The myocardial
      injury induced by DM is associated with the up-regulation of GSK-3beta. LiCl
      inhibited the expression of GSK-3beta and myocardial apoptosis in diabetic
      myocardium.

PMID- 30237228
TI  - Graduates are being blocked from entering medical school, students warn.

PMID- 30237227
TI  - An allosteric mechanism of inactivation in the calcium-dependent chloride channel
      BEST1.
AB  - Bestrophin proteins are calcium (Ca2+)-activated chloride channels. Mutations in
      bestrophin 1 (BEST1) cause macular degenerative disorders. Whole-cell recordings
      show that ionic currents through BEST1 run down over time, but it is unclear
      whether this behavior is intrinsic to the channel or the result of cellular
      factors. Here, using planar lipid bilayer recordings of purified BEST1, we show
      that current rundown is an inherent property of the channel that can now be
      characterized as inactivation. Inactivation depends on the cytosolic
      concentration of Ca2+, such that higher concentrations stimulate inactivation. We
      identify a C-terminal inactivation peptide that is necessary for inactivation and
      dynamically interacts with a receptor site on the channel. Alterations of the
      peptide or its receptor dramatically reduce inactivation. Unlike inactivation
      peptides of voltage-gated channels that bind within the ion pore, the receptor
      for the inactivation peptide is on the cytosolic surface of the channel and
      separated from the pore. Biochemical, structural, and electrophysiological
      analyses indicate that binding of the peptide to its receptor promotes
      inactivation, whereas dissociation prevents it. Using additional mutational
      studies we find that the "neck" constriction of the pore, which we have
      previously shown to act as the Ca2+-dependent activation gate, also functions as
      the inactivation gate. Our results indicate that unlike a ball-and-chain
      inactivation mechanism involving physical occlusion of the pore, inactivation in
      BEST1 occurs through an allosteric mechanism wherein binding of a peptide to a
      surface-exposed receptor controls a structurally distant gate.

PMID- 30237229
TI  - Growth Hormone Therapy for a Child With Severe Cognitive Impairment.
AB  - The expansion of growth hormone therapy over the last 3 decades has allowed for
      treatment of short stature for more children, resulting in increased height for
      many. However, treatment of idiopathic short stature remains controversial.
      Treatment decisions for disabled children with idiopathic short stature are even
      more complicated. We discuss a specific case of short stature in a disabled child
      and grapple with the ethical issues involved in the use of growth hormone.

PMID- 30237230
TI  - General Pediatricians and Value-Based Payments.
AB  - BACKGROUND AND OBJECTIVE: In an effort to transform the health care system,
      payers and physicians are experimenting with new payment models, mostly in an
      effort to move from a volume-based system to one based on value. We conducted a
      national survey to evaluate pediatricians' experience with and views about new
      value-based models of payment. METHODS: An American Academy of Pediatrics 2016
      member survey was used to assess provider and practice characteristics, provider
      experience with value-based payments (VBPs) (through accountable care
      organizations [ACOs] or pay for quality performance), and provider views about
      new payment models. We used descriptive statistics and multivariable logistic
      regression models to examine relationships between experience and views. RESULTS:
      The survey response rate was 48.7% (n = 786 of 1614). Of practicing general
      pediatricians, 52% reported experience with VBP, 32% believed payment for quality
      metrics have a "positive impact" on pediatricians' ability to provide quality
      care for patients, and 12% believed ACOs have a positive impact. Adjusting for
      covariates, respondents experienced with payments for quality metrics (adjusted
      odds ratio: 2.01; 95% confidence interval 1.26-3.19) and ACOs (odds ratio: 6.68;
      95% confidence interval 3.55-13.20) were more likely to report a positive impact.
      CONCLUSIONS: Although experience and views vary, just more than half of surveyed
      pediatricians report receiving some form of VBP. Pediatricians reporting this
      experience are more likely to feel that these payment models have a positive
      impact on patient care when compared with pediatricians without this experience.

PMID- 30237232
TI  - In This Issue of Diabetes Care.

PMID- 30237231
TI  - Alcohol must be recognised as a drug.

PMID- 30237233
TI  - A Perspective on the Accuracy of Blood Glucose Meters During Pregnancy.
AB  - Blood glucose monitoring is fundamental for hyperglycemia management during
      pregnancy, but are the devices up to the job? Studies assessing the accuracy of
      10 commercially available glucose meters during pregnancy showed that although
      >98-99% of the meter values were in the acceptable zones of the error grid for
      the majority of the meters, the meter performance varied, with the majority
      showing positive bias and a few showing minimal negative bias. The mean
      difference between meter and laboratory plasma values varied between -0.33 and
      0.73 mmol/L. Three meters showed deviations from laboratory results with a change
      in maternal hematocrit levels. No meters had a total analytical error <5%, and no
      studies evaluated meters using recent International Organization for
      Standardization 15197:2013 criteria. The Continuous Glucose Monitoring in Women
      With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) recently showed that an
      antenatal continuous glucose monitoring system (CGMS), as an adjunct to capillary
      monitoring, was associated with a lower incidence of large-for-gestational-age
      babies, fewer neonatal intensive care unit admissions (>24 h), and a lower
      incidence of neonatal hypoglycemia. The flash glucose monitoring system shows
      good accuracy in pregnant women but has not been marketed widely in the U.S. We
      suggest that meters cannot be assumed to be sufficiently accurate during
      pregnancy and that manufacturers should ensure a total error <5%, with bias and
      imprecision <2% during pregnancy. Large studies are needed to evaluate the
      usefulness of CGMS among pregnant women with type 2 diabetes and gestational
      diabetes mellitus.

PMID- 30237234
TI  - John E. Gerich: Father of Modern Physiology of Glucose Homeostasis,
      Counterregulation to Hypoglycemia, and Mechanistic Treatment of Diabetes.

PMID- 30237237
TI  - Seven days in medicine: 12-18 September 2018.

PMID- 30237235
TI  - "Fat Shadows" From DXA for the Qualitative Assessment of Lipodystrophy: When a
      Picture Is Worth a Thousand Numbers.
AB  - OBJECTIVE: Lipodystrophy syndromes are a heterogeneous group of disorders
      associated with selective absence of fat. Currently, the diagnosis is established
      only clinically. RESEARCH DESIGN AND METHODS: We developed a new method from DXA
      scans called a "fat shadow," which is a color-coded representation highlighting
      only the fat tissue. We conducted a blinded retrospective validation study to
      assess its usefulness for the diagnosis of lipodystrophy syndromes. RESULTS: We
      evaluated the fat shadows from 16 patients (11 female and 5 male) with
      generalized lipodystrophy (GL), 57 (50 female and 7 male) with familial partial
      lipodystrophy (FPLD), 2 (1 female and 1 male) with acquired partial
      lipodystrophy, and 126 (90 female and 36 male) control subjects. FPLD was
      differentiated from control subjects with 85% sensitivity and 96% specificity
      (95% CIs 72-93 and 91-99, respectively). GL was differentiated from nonobese
      control subjects with 100% sensitivity and specificity (95% CIs 79-100 and 92
      100, respectively). CONCLUSIONS: Fat shadows provided sufficient qualitative
      information to infer clinical phenotype and differentiate these patients from
      appropriate control subjects. We propose that this method could be used to
      support the diagnosis.

PMID- 30237238
TI  - Muscle fibers bear a larger fraction of passive muscle tension in frogs compared
      with mice.
AB  - Differences in passive muscle mechanical properties between amphibians and
      mammals have led to differing hypotheses on the functional role of titin in
      skeletal muscle. Early studies of frog muscle clearly demonstrated intracellular
      load bearing by titin, but more recent structural and biological studies in mice
      have shown that titin may serve other functions. Here, we present biomechanical
      studies of isolated frog and mouse fibers, and fiber bundles to compare the
      relative importance of intracellular versus extracellular load bearing in these
      species. Mouse bundles exhibited increased modulus compared with fibers on the
      descending limb of the length-tension curve, reaching a 2.4-fold elevation at the
      longest sarcomere lengths. By contrast, frog fibers and bundles had approximately
      the same modulus at all sarcomere lengths tested. These findings suggest that in
      the mouse, both muscle fibers and the ECM are involved in bearing whole muscle
      passive tension, which is distinct from the load bearing process in frog muscle,
      where titin bears the majority of whole muscle passive tension.

PMID- 30237240
TI  - Neuromechanical coupling within the human triceps surae and its consequence on
      individual force-sharing strategies.
AB  - Little is known about the factors that influence the coordination of synergist
      muscles that act across the same joint, even during single-joint isometric tasks.
      The overall aim of this study was to determine the nature of the relationship
      between the distribution of activation and the distribution of force-generating
      capacity among the three heads of the triceps surae [soleus (SOL), gastrocnemius
      medialis (GM) and gastrocnemius lateralis (GL)]. Twenty volunteers performed
      isometric plantarflexions, during which the activation of GM, GL and SOL was
      estimated using electromyography (EMG). Functional muscle physiological cross
      sectional area (PCSA) was estimated using imaging techniques and was considered
      as an index of muscle force-generating capacity. The distribution of activation
      and PCSA among the three muscles varied greatly between participants. A
      significant positive correlation between the distribution of activation and the
      distribution of PCSA was observed when considering the two bi-articular muscles
      at intensities <=50% of the maximal contraction (0.51<r<0.62). Specifically, the
      greater the PCSA of GM compared with GL, the stronger bias of activation to the
      GM. There was no significant correlation between monoarticular and biarticular
      muscles. A higher contribution of GM activation compared with GL activation was
      associated with lower triceps surae activation (-0.66<r<-0.42) and metabolic cost
      (-0.74<r<-0.52) for intensities >=30% of the maximal contraction. Considered
      together, an imbalance of force between the three heads was observed, the
      magnitude of which varied greatly between participants. The origin and
      consequences of these individual force-sharing strategies remain to be
      determined.

PMID- 30237239
TI  - Interaction between step-to-step variability and metabolic cost of transport
      during human walking.
AB  - Minimizing the metabolic cost of transport can affect selection of the preferred
      walking speed. While many factors can affect metabolic cost of transport during
      human walking, its interaction with step-to-step variability is unclear. Here, we
      aimed to determine the interaction between metabolic cost of transport and step
      length variability during human walking at different speeds. In particular, two
      aspects of step length variability were analyzed: the amount of variations
      ('variations') and the organization of the step-to-step fluctuations
      ('fluctuations'). Ten healthy, young participants walked on a treadmill at five
      speeds, ranging from 0.75 to 1.75 m s-1 Metabolic cost of transport, step length
      variations (coefficient of variation) and step length fluctuations (quantified
      via detrended fluctuation analysis) were calculated. A mixed-model ANOVA revealed
      that variations and walking speed were strong predictors of metabolic cost of
      transport (R 2=0.917, P<0.001), whereas fluctuations were not. Preferred walking
      speed (1.05+/-0.20 m s-1) was not significantly different from the speed at which
      metabolic cost of transport was minimized (1.04+/-0.05 m s-1; P=0.792), nor from
      the speed at which fluctuations were most persistent (1.00+/-0.41 m s-1;
      P=0.698). The minimization of variations occurred at a faster speed (1.56+/-0.17
      m s-1) than the preferred walking speed (P<0.001). Step length variations likely
      affect metabolic cost of transport because greater variations are indicative of
      suboptimal, mechanically inefficient steps. Fluctuations have little or no effect
      on metabolic cost of transport, but still may relate to preferred walking speed.

PMID- 30237241
TI  - Taurine activates glycine and GABAA receptor currents in anoxia-tolerant painted
      turtle pyramidal neurons.
AB  - Unlike anoxia-intolerant mammals, painted turtles can survive extended periods
      without oxygen. This is partly accomplished by an anoxia-mediated increase in
      gamma-aminobutyric acid (GABA) release, which activates GABA receptors and
      mediates spike arrest in turtle neurons via shunting inhibition. Extracellular
      taurine levels also increase during anoxia; why this occurs is unknown but it is
      speculated that glycine and/or GABAA/B receptors are involved. Given the general
      importance of inhibitory neurotransmission in the anoxia-tolerant painted turtle
      brain, we investigated the function of taurine as an inhibitory neuromodulator in
      turtle pyramidal neurons. Using whole-cell patch-clamp electrophysiological
      methods to record from neurons within a cortical brain sheet, we found that
      taurine depolarized membrane potential by ~8 mV, increased whole-cell conductance
      ~2-fold, and induced an inward current that possessed characteristics similar to
      GABA- and glycine-evoked currents. These effects were mitigated following glycine
      receptor antagonism with strychnine and GABAA receptor antagonism with gabazine,
      bicuculine or picrotoxin, but were unchanged following GABAB or glutamatergic
      receptor inhibition. These data indicate that a high concentration of taurine in
      vitro mediates its effects through both glycine and GABAA receptors, and suggests
      that taurine, in addition to GABA, inhibits neuronal activity during anoxia in
      the turtle cortex.

PMID- 30237242
TI  - Functional redundancy of frizzled 3 and frizzled 6 in planar cell polarity
      control of mouse hair follicles.
AB  - The orientation of mouse hair follicles is controlled by the planar cell polarity
      (PCP) pathway. Mutations in PCP genes result in two categories of hair mis
      orientation phenotype: randomly oriented and vertically oriented to the skin
      surface. Here, we demonstrate that the randomly oriented hair phenotype observed
      in frizzled 6 (Fzd6) mutants results from a partial loss of the polarity, due to
      the functional redundancy of another closely related frizzled gene, Fzd3 Double
      knockout of Fzd3 and Fzd6 globally, or only in the skin, led to vertically
      oriented hair follicles and a total loss of anterior-posterior polarity.
      Furthermore, we provide evidence that, contrary to the prevailing model,
      asymmetrical localization of the Fzd6 protein is not observed in skin epithelial
      cells. Through transcriptome analyses and in vitro studies, we show collagen
      triple helix repeat containing 1 (Cthrc1) to be a potential downstream effector
      of Fzd6, but not of Fzd3. Cthrc1 binds directly to the extracellular domains of
      Fzd3 and Fzd6 to enhance the Wnt/PCP signaling. These results suggest that Fzd3
      and Fzd6 play a redundant role in controlling the polarity of developing skin,
      but through non-identical mechanisms.

PMID- 30237243
TI  - Neuropilins guide preganglionic sympathetic axons and chromaffin cell precursors
      to establish the adrenal medulla.
AB  - The adrenal medulla is composed of neuroendocrine chromaffin cells that secrete
      adrenaline into the systemic circulation to maintain physiological homeostasis
      and enable the autonomic stress response. How chromaffin cell precursors colonise
      the adrenal medulla and how they become connected to central nervous system
      derived preganglionic sympathetic neurons remain largely unknown. By combining
      lineage tracing, gene expression studies, genetic ablation and the analysis of
      mouse mutants, we demonstrate that preganglionic axons direct chromaffin cell
      precursors into the adrenal primordia. We further show that preganglionic axons
      and chromaffin cell precursors require class 3 semaphorin (SEMA3) signalling
      through neuropilins (NRP) to target the adrenal medulla. Thus, SEMA3 proteins
      serve as guidance cues to control formation of the adrenal neuroendocrine system
      by establishing appropriate connections between preganglionic neurons and adrenal
      chromaffin cells that regulate the autonomic stress response.

PMID- 30237245
TI  - Enantiodivergent Pd-catalyzed C-C bond formation enabled through ligand
      parameterization.
AB  - Despite the enormous potential for the use of stereospecific cross-coupling
      reactions to rationally manipulate the three-dimensional structure of organic
      molecules, the factors that control the transfer of stereochemistry in these
      reactions remain poorly understood. Here we report a mechanistic and synthetic
      investigation into the use of enantioenriched alkylboron nucleophiles in
      stereospecific Pd-catalyzed Suzuki cross-coupling reactions. By developing a
      suite of molecular descriptors of phosphine ligands, we could apply predictive
      statistical models to select or design distinct ligands that respectively
      promoted stereoinvertive and stereoretentive cross-coupling reactions.
      Stereodefined branched structures were thereby accessed through the predictable
      manipulation of absolute stereochemistry, and a general model for the mechanism
      of alkylboron transmetallation was proposed.

PMID- 30237244
TI  - Characterization of the ventricular-subventricular stem cell niche during human
      brain development.
AB  - Human brain development proceeds via a sequentially transforming stem cell
      population in the ventricular-subventricular zone (V-SVZ). An essential, but
      understudied, contributor to V-SVZ stem cell niche health is the multi-ciliated
      ependymal epithelium, which replaces stem cells at the ventricular surface during
      development. However, reorganization of the V-SVZ stem cell niche and its
      relationship to ependymogenesis has not been characterized in the human brain.
      Based on comprehensive comparative spatiotemporal analyses of cytoarchitectural
      changes along the mouse and human ventricle surface, we uncovered a distinctive
      stem cell retention pattern in humans as ependymal cells populate the surface of
      the ventricle in an occipital-to-frontal wave. During perinatal development,
      ventricle-contacting stem cells are reduced. By 7 months few stem cells are
      detected, paralleling the decline in neurogenesis. In adolescence and adulthood,
      stem cells and neurogenesis are not observed along the lateral wall. Volume,
      surface area and curvature of the lateral ventricles all significantly change
      during fetal development but stabilize after 1 year, corresponding with the wave
      of ependymogenesis and stem cell reduction. These findings reveal normal human V
      SVZ development, highlighting the consequences of disease pathologies such as
      congenital hydrocephalus.

PMID- 30237246
TI  - Generation of human oogonia from induced pluripotent stem cells in vitro.
AB  - Human in vitro gametogenesis may transform reproductive medicine. Human
      pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like
      cells (hPGCLCs); however, further differentiation to a mature germ cell has not
      been achieved. Here, we show that hPGCLCs differentiate progressively into
      oogonia-like cells during a long-term in vitro culture (approximately 4 months)
      in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells.
      The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming-genome
      wide DNA demethylation, imprint erasure, and extinguishment of aberrant DNA
      methylation in hPSCs-and acquire an immediate precursory state for meiotic
      recombination. Furthermore, the inactive X chromosome shows a progressive
      demethylation and reactivation, albeit partially. These findings establish the
      germline competence of hPSCs and provide a critical step toward human in vitro
      gametogenesis.

PMID- 30237247
TI  - Photon-mediated interactions between quantum emitters in a diamond nanocavity.
AB  - Photon-mediated interactions between quantum systems are essential for realizing
      quantum networks and scalable quantum information processing. We demonstrate such
      interactions between pairs of silicon-vacancy (SiV) color centers coupled to a
      diamond nanophotonic cavity. When the optical transitions of the two color
      centers are tuned into resonance, the coupling to the common cavity mode results
      in a coherent interaction between them, leading to spectrally resolved
      superradiant and subradiant states. We use the electronic spin degrees of freedom
      of the SiV centers to control these optically mediated interactions. Such
      controlled interactions will be crucial in developing cavity-mediated quantum
      gates between spin qubits and for realizing scalable quantum network nodes.

PMID- 30237248
TI  - Autophagy-dependent cell death - where, how and why a cell eats itself to death.
AB  - Autophagy as a means of cell killing was first advanced by Clark's phenotypic
      description of 'Type II autophagic cell death' in 1990. However, this phenomenon
      later came into question, because the presence of autophagosomes in dying cells
      does not necessarily signify that autophagy is the cause of demise, but rather
      may reflect the efforts of the cell to prevent it. Resolution of this issue comes
      from a more careful definition of autophagy-dependent cell death (ADCD) as a
      regulated cell death that is shown experimentally to require different components
      of the autophagy machinery without involvement of alternative cell death
      pathways. Following these strict criteria, ADCD has been validated in both lower
      model organisms and mammalian cells, highlighting its importance for
      developmental and pathophysiological cell death. Recently, researchers have
      defined additional morphological criteria that characterize ADCD and begun to
      explore how the established, well-studied autophagy pathway is subverted from a
      survival to a death function. This Review explores validated models of ADCD and
      focuses on the current understanding of the mechanisms by which autophagy can
      kill a cell.

PMID- 30237249
TI  - Axial morphology and 3D neurocranial kinematics in suction-feeding fishes.
AB  - Many suction-feeding fish use neurocranial elevation to expand the buccal cavity
      for suction feeding, a motion necessarily accompanied by the dorsal flexion of
      joints in the axial skeleton. How much dorsal flexion the axial skeleton
      accommodates and where that dorsal flexion occurs may vary with axial skeletal
      morphology, body shape and the kinematics of neurocranial elevation. We measured
      three-dimensional neurocranial kinematics in three species with distinct body
      forms: laterally compressed Embiotoca lateralis, fusiform Micropterus salmoides,
      and dorsoventrally compressed Leptocottus armatus The area just caudal to the
      neurocranium occupied by bone was 42+/-1.5%, 36+/-1.8% and 22+/-5.5% (mean+/
      s.e.m.; N=3, 6, 4) in the three species, respectively, and the epaxial depth also
      decreased from E. lateralis to L. armatus Maximum neurocranial elevation for each
      species was 11, 24 and 37 degrees , respectively, consistent with a hypothesis
      that aspects of axial morphology and body shape may constrain neurocranial
      elevation. Mean axis of rotation position for neurocranial elevation in E.
      lateralis, M. salmoides and L. armatus was near the first, third and fifth
      intervertebral joints, respectively, leading to the hypothesis of a similar
      relationship with the number of intervertebral joints that flex. Although future
      work must test these hypotheses, our results suggest the relationships merit
      further inquiry.

PMID- 30237252
TI  - An RNA bestiary in splicing-mutant MDS.

PMID- 30237250
TI  - Chronic Medical Conditions and CA125 Levels among Women without Ovarian Cancer.
AB  - BACKGROUND: Randomized trials using the biomarker cancer antigen (CA) 125, with
      or without pelvic ultrasound, have failed to show a clear benefit of general
      population screening for ovarian cancer. In part, this may be due to a lack of
      information about conditions, besides ovarian cancer, that can alter CA125 levels
      and affect specificity or sensitivity. We evaluated the association between
      common medical conditions and CA125 levels among women without ovarian cancer.
      METHODS: We used data and specimens from 2,004 women without ovarian cancer who
      participated in the New England Case Control study between 1992 and 2008.
      Participants completed in-person interviews and donated blood samples at
      enrollment. We measured CA125 using the CA125II assay and calculated the
      association between medical conditions and log-transformed CA125 using linear
      regression. RESULTS: The median age of participants was 53 years and 1,119 (56%)
      were postmenopausal. The average CA125 level was 14.5 units/mL for premenopausal
      and 11.7 for postmenopausal women. Among premenopausal women, CA125 was
      significantly lower for women with colon polyps (P = 0.06) and hysterectomy (P =
      0.01) and significantly higher with endometriosis (P = 0.05). CA125 was also
      significantly higher in premenopausal women with coronary artery disease (CVD) (P
      < 0.01, n = 2 cases) but not among postmenopausal with CVD (n = 79). Furthermore,
      among postmenopausal women, CA125 was significantly lower for women with
      osteoporosis, hypercholesterolemia, and osteoarthritis (P = 0.03, 0.02, and 0.01
      respectively) and higher for women with a history of inflammatory bowel disease
      (P = 0.04). CONCLUSIONS: Several chronic diseases are associated with CA125,
      which could influence the interpretation of CA125 in the context of ovarian
      cancer screening. IMPACT: Consideration of chronic medical conditions may be
      necessary to interpret CA125 values.

PMID- 30237253
TI  - CRISPRing the CRL4CRBN RING in multiple myeloma.

PMID- 30237254
TI  - SRP54 and a need for a new neutropenia nosology.

PMID- 30237251
TI  - Methylation of High-Risk Human Papillomavirus Genomes Are Associated with
      Cervical Precancer in HIV-Positive Women.
AB  - BACKGROUND: HIV-positive women are at substantial risk of HPV-associated cervical
      neoplasia caused by high-risk (HR) HPVs. Methylation of the HPV genome is
      associated with cervical intraepithelial neoplasia grade 3 (CIN3) in HIV-negative
      women, yet it is unknown whether this holds true for HIV-positive women. METHODS:
      We designed a case-control study within the Women's Interagency HIV Study (WIHS)
      cohort comparing HIV-positive CIN3 cases (N = 72) to HIV-positive controls
      without detectable CIN2+. The unit of analysis and matching was HPV-type
      infection. Cases with >=2 HR-HPV types (N = 23; 32%) had a separate control for
      each HR-HPV type. We developed and utilized next-generation sequencing (NGS)
      methylation assays for 12 different HR-HPVs, focusing on CpG sites in the L1/L2
      regions. RESULTS: Significant case-control differences in individual CpG site
      methylation levels were observed for multiple alpha-9 (HPV16/31/35/58) and alpha
      7 HPV (HPV18/39/45) types, based on dichotomization of tertile levels (T3 vs. T1
      and T2). Analyses combining homologous CpG sites [e.g., HPV16-L1-5608/HPV31-L1
      5521/HPV35-L2L1-5570; OR = 7.28; 95% confidence interval (CI): 2.75-19.3], and
      (e.g., HPV18-L1-7062/HPV45-L1-7066; OR = 6.94; 95% CI: 1.23-39.3) were
      significant in separate case-control comparisons. In cases with multiple HR-HPVs,
      we tested and confirmed the hypothesis that one HR-HPV type would have higher
      methylation than other types detected, consistent with there being a single HR
      HPV causally related to a lesion. CONCLUSIONS: CIN3 is associated with elevated
      L1/L2 CpG methylation levels in HIV-positive women. IMPACT: HPV DNA CpG
      methylation is a promising triage option in HIV-positive women testing positive
      for HR-HPV types and provides risk attribution in women with multiple HPV type
      infections.

PMID- 30237255
TI  - Platelets in malaria pathogenesis.

PMID- 30237256
TI  - A rare case of renal intravascular NK/T-cell lymphoma.

PMID- 30237258
TI  - Aberrant splicing in splicing factor mutant MDS.

PMID- 30237257
TI  - Heeney MM, Guo D, De Falco L, et al. Normalizing hepcidin predicts TMPRSS6
      mutation status in patients with chronic iron deficiency. Blood. 2018;132(4):448
      452.

PMID- 30237259
TI  - Decreasing Racemic Epinephrine for Bronchiolitis in an Academic Children's
      Hospital.
AB  - BACKGROUND AND OBJECTIVES: Bronchiolitis is a leading cause of pediatric
      hospitalizations in the United States. Although the American Academy of
      Pediatrics recommends against routine use of bronchodilators in bronchiolitis
      management, racemic epinephrine was persistently used for this purpose at Le
      Bonheur Children's Hospital. Our aim was to decrease racemic epinephrine use for
      bronchiolitis by 50% within 8 months. METHODS: Our multidisciplinary team used
      the Institute for Healthcare Improvement's Model for Improvement to develop an
      aim statement, choose metrics, and perform plan-do-study-act cycles to reduce
      racemic epinephrine use. We used focused education through in-person and online
      methods and provided direct feedback to residents, respiratory therapists, and
      nurses primarily caring for these children. The percentage of all patients
      admitted for bronchiolitis receiving at least 1 dose of racemic epinephrine was
      collected from the medical record and recorded on statistical process control
      charts for distribution to their work areas. Albuterol use and length of stay
      were collected as balancing measures. We used statistical process control charts
      to establish special cause variation and identify statistically significant
      differences in our measures. RESULTS: During our intervention period, the
      percentage of bronchiolitis patients receiving at least 1 dose of racemic
      epinephrine to treat bronchiolitis decreased from an average of 26% to 5%, and
      similarly, albuterol use decreased from an average of 48% to 34%. There was no
      clinically significant difference in length of stay. CONCLUSIONS: Using a
      multidisciplinary approach and focused education techniques may be an effective
      way to reduce racemic epinephrine use for children with bronchiolitis.

PMID- 30237260
TI  - Bone marrow mesenchymal stem/stromal cells from risk-stratified acute myeloid
      leukemia patients are anti-inflammatory in in vivo preclinical models of
      hematopoietic reconstitution and severe colitis.
AB  - Acute myeloid leukemia represents a heterogeneous group of disorders
      characterized by the rapid expansion of immature myeloid cells (blasts) in the
      bone marrow. There is wide disease heterogeneity and patient risk-stratification
      principally relies on cytogenetic-molecular data. Bone-marrow mesenchymal
      stem/stromal cells are key components of the hematopoietic niche thought to
      contribute to leukemia pathogenesis. We recently reported a correlation between
      behaviors of bone-marrow mesenchymal stem/stromal cells from acute myeloid
      leukemia patients in vitro and overall survival. To elaborate on this finding, we
      investigated the capacity of bone-marrow mesenchymal stem/stromal cells from risk
      stratified de novo acute myeloid leukemia patients to regulate the homeostasis of
      healthy CD34+ hematopoietic stem/progenitor cells, and to exert anti-inflammatory
      effects in vivo in a pre-clinical model of severe acute colitis. We report that
      regardless of risk-group, bone-marrow mesenchymal stem/stromal cells from acute
      myeloid leukemia patients support, similar to those derived from healthy bone
      marrow the survival, proliferation, differentiation and clonogenecity of CD34+
      cells in vitro, and the in vivo immune deficient mice repopulating assays.
      Additionally, bone-marrow mesenchymal stem/stromal cells from acute myeloid
      leukemia patients were capable of reversing the inflammatory phenotype in
      preclinical models of acute severe colitis, showing a greater anti-inflammatory
      capacity compared to those derived from healthy bone marrow. Collectively, bone
      marrow mesenchymal stem/stromal cells from acute myeloid leukemia patients retain
      the capacity to support healthy hematopoietic stem/progenitor cells and can
      suppress inflammation in vivo.

PMID- 30237261
TI  - The allo-HLA-DP restricted T cell repertoire provoked by allogeneic dendritic
      cells contains T cells that show restricted recognition of hematopoietic cells
      including primary malignant cells.
AB  - Stem cell grafts from 10/10 HLA-matched unrelated donors are often mismatched for
      HLA-DP. In some patients, donor T cell responses targeting the mismatched HLA-DP
      allele(s) have been found to induce a specific graft-versus-leukemia effect
      without coinciding graft-versus-host disease, whereas in other cases significant
      graft-versus-host disease occurred. Cell-lineage-specific recognition patterns
      within the allo-HLA-DP specific donor T cell repertoire could explain the
      differential clinical effects mediated by donor T cells after HLA-DP mismatched
      allogeneic-stem-cell-transplantation. To unravel the composition of the HLA-DP T
      cell repertoire, donor T cell responses were provoked by in vitro stimulation
      with allogeneic HLA-DP mismatched monocyte-derived dendritic cells. A strategy
      including depletion of reactivity against autologous dendritic cells allowed
      efficient identification and enrichment of allo-reactive T cells upon stimulation
      with HLA-DP mismatched dendritic cells. In this study we elucidated that the allo
      HLA-DP restricted T cell repertoire contained T cells with differential cell
      lineage-specific recognition profiles. As expected, part of the allo-HLA-DP
      restricted T cells showed broad recognition of a variety of hematopoietic and non
      hematopoietic cell types expressing the targeted mismatched HLA-DP allele.
      However, a significant proportion of the allo-HLA-DP restricted T cells showed
      restricted recognition of hematopoietic cells, including primary malignant cells,
      or even restricted recognition of only myeloid cells, including dendritic cells
      and primary acute-myeloid-leukemia samples, but not of other hematopoietic and
      non-hematopoietic cell types. These data demonstrate that the allo-HLA-DP
      specific T cell repertoire contains T cells that show restricted recognition of
      hematopoietic cells, which may contribute to specific graft-versus-leukemia
      effect reactivity without coinciding graft-versus-host disease.

PMID- 30237262
TI  - Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and
      dexamethasone in relapsed or refractory multiple myeloma: updated analysis of
      POLLUX.
AB  - : In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly
      reduced risk of progression/death versus lenalidomide/dexamethasone alone in
      relapsed/refractory multiple myeloma. We provide one additional year of follow-up
      and include the effect on minimal residual disease and in clinically relevant
      subgroups. After 25.4 months of follow-up, daratumumab plus
      lenalidomide/dexamethasone prolonged progression-free survival versus
      lenalidomide/dexamethasone alone (median not reached vs 17.5 months; hazard
      ratio, 0.41; 95% confidence interval, 0.31-0.53; P <0.0001). The overall response
      rate was 92.9% versus 76.4%, and 51.2% versus 21.0% achieved a complete response
      or better, respectively (both P <0.0001). At the 10e5 sensitivity threshold,
      26.2% versus 6.4% were minimal residual disease-negative, respectively (P
      <0.0001). Post hoc analyses of clinical relevant patient subgroups demonstrated
      that progression-free survival was significantly prolonged for daratumumab plus
      lenalidomide/dexamethasone versus lenalidomide/dexamethasone regardless of number
      of prior lines of therapy. Patients previously treated with lenalidomide or
      thalidomide and those refractory to bortezomib received similar benefits (all P
      <0.01). Treatment benefit with daratumumab plus lenalidomide/dexamethasone was
      maintained in high-risk patients (median progression-free survival 22.6 vs 10.2
      months; hazard ratio, 0.53; 95% confidence interval, 0.25-1.13; P = 0.0921) and
      patients with treatment-free intervals of >12 and <=12 months, >6 and <=6 months.
      No new safety signals were observed. In relapsed/refractory multiple myeloma
      patients, daratumumab plus lenalidomide/dexamethasone continued to improve
      progression-free survival and deepen responses versus lenalidomide/dexamethasone.
      TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02076009.

PMID- 30237263
TI  - Clonally related diffuse large B-cell lymphoma and interdigitating dendritic cell
      sarcoma sharing MYC translocation.

PMID- 30237265
TI  - Machine learning reveals chronic graft-versus-host disease phenotypes and
      stratifies survival after stem cell transplant for hematologic malignancies.
AB  - The application of machine learning in medicine has been productive in multiple
      fields, and has not previously been applied to analyze the complexity of chronic
      graft-versus-host disease organ involvement. Chronic graft-versus-host disease is
      classified by an overall composite score of mild, moderate or severe, which may
      overlook clinically relevant patterns in organ involvement. Here we applied a
      novel computational approach to chronic graft-versus-host disease with the goal
      of identifying phenotypic groups based on the subcomponents of the National
      Institutes of Health (NIH) Consensus Criteria. Computational analysis revealed 7
      distinct patient groups with contrasting clinical risks. The high-risk group had
      an inferior overall survival compared to the low-risk group (HR 2.24 [95% CI 1.36
      3.68]), and was independent of severity as measured by the NIH criteria. To test
      clinical applicability, knowledge was translated into a simplified clinical
      prognostic decision tree. Groups identified by the decision tree also stratified
      outcomes and closely matched those from the original analysis. Patients in the
      high and intermediate-risk decision tree groups had significantly shorter overall
      survival than those in the low-risk group (HR 2.79 [1.58-4.91] and HR 1.78 [1.06
      3.01], respectively). Machine learning and other computational analyses may
      better reveal biomarkers and stratify risk than the current approach based on
      cumulative severity. This approach could now be explored in other disease models
      with complex clinical phenotypes. External validation must be completed prior to
      clinical application. Ultimately, this approach has the potential to reveal
      distinct pathophysiological mechanisms that may underlie clusters.
      Clinicaltrials.gov identifier: NCT00637689.

PMID- 30237264
TI  - Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone
      in relapsed or refractory multiple myeloma: updated analysis of CASTOR.
AB  - : Daratumumab, a CD38 human monoclonal antibody, demonstrated significant
      clinical activity in combination with bortezomib and dexamethasone versus
      bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3
      study in relapsed and/or refractory multiple myeloma. A post hoc analysis based
      on treatment history and longer follow-up is presented. After 19.4 (range: 0 to
      27.7) months of median follow-up, daratumumab plus bortezomib and dexamethasone
      prolonged progression-free survival (median: 16.7 versus 7.1 months; hazard
      ratio, 0.31; 95% confidence interval, 0.24-0.39; P <0.0001) and improved the
      overall response rate (83.8% versus 63.2%; P <0.0001) compared with bortezomib
      and dexamethasone alone. The progression-free survival benefit of daratumumab
      plus bortezomib and dexamethasone was most apparent in patients with 1 prior line
      of therapy (median: not reached versus 7.9 months; hazard ratio, 0.19; 95%
      confidence interval, 0.12-0.29; P <0.0001). Daratumumab plus bortezomib and
      dexamethasone was also superior to bortezomib and dexamethasone alone in
      subgroups based on prior treatment exposure (bortezomib, thalidomide, or
      lenalidomide), lenalidomide-refractory status, time since last therapy (<=12,
      >12, <=6, or >6 months), or cytogenetic risk. Minimal residual disease-negative
      rates were >2.5-fold higher with daratumumab across subgroups. The safety profile
      of daratumumab plus bortezomib and dexamethasone remained consistent with longer
      follow-up. Daratumumab plus bortezomib and dexamethasone demonstrated significant
      clinical activity across clinically relevant subgroups and provided the greatest
      benefit to patients treated at first relapse. TRIAL REGISTRATION:
      clinicaltrials.gov identifier: NCT02136134.

PMID- 30237266
TI  - Allogeneic transplantation of multiple myeloma patients may allow long-term
      survival in carefully selected patients with acceptable toxicity and preserved
      quality of life.
AB  - Despite significantly improved survival and response rates in patients diagnosed
      with multiple myeloma, it still remains an incurable disease with a poor outcome
      especially in high-risk groups. Allogeneic stem cell transplantation offers a
      potentially curative option but is discussed controversially due to considerable
      treatment related toxicity. We analyzed 109 consecutive myeloma patients who
      received reduced-intensity conditioning allogeneic transplantation at the
      Freiburg University Medical Center between 2000 and 2017. Although most patients
      were heavily pretreated in high-risk constellations, the overall response rate
      was high with 70%, the median overall survival 39.2 and the median progression
      free survival 14.2 months, with a median follow-up of 71.5 months. Survival was
      significantly better in patients with response to previous therapies than in
      those with progressive disease (median OS 65 vs. 11.5 months, p=0.003; median PFS
      18.4 vs. 5.1 months, p=0.001). Moreover, survival of patients transplanted in
      first-line was significantly prolonged compared to relapsed/refractory disease
      (median OS not reached vs. 21.6 months, p<0.001; median PFS 47.7 vs. 9.6 months,
      p<0.001). The non-relapse mortality was relatively low with a cumulative
      incidence of 12.4% at 10 years. Acute graft-versus-host disease II-IV occurred in
      25%, moderate or severe chronic graft-versus-host disease in 24%. Quality of life
      assessed with the revised Myeloma Comorbidity Index before and after
      transplantation remained unchanged. Our data suggest that allogeneic
      transplantation in the context of novel immunotherapeutic approaches may enable
      long-term survival and even potential cure in a carefully selected subgroup of
      high-risk multiple myeloma patients with acceptable toxicity and preserved
      quality of life.

PMID- 30237267
TI  - A gain of function variant in PIEZO1 (E756del) and sickle cell disease.

PMID- 30237268
TI  - Transglutaminase 2 programs differentiating acute promyelocytic leukemia cells in
      all-trans retinoic acid treatment to inflammatory stage through NF-kB activation.
AB  - Differentiation syndrome is a life-threatening complication arising during
      retinoid treatment of acute promyelocytic leukemia. Administration of all-trans
      retinoic acid leads to significant changes in gene expression, among the most
      induced of which is transglutaminase 2, which is not normally expressed in
      neutrophil granulocytes. To evaluate the pathophysiological function of
      transglutaminase 2 in the context of immunological function and disease outcomes,
      such as excessive superoxide anion, cytokine, and chemokine production in
      differentiated NB4 cells, we used an NB4 transglutaminase knock-out cell line and
      a transglutaminase inhibitor, NC9, which inhibits both transamidase- and
      guanosine triphosphate-binding activities, to clarify transglutaminase's
      contribution to the development of potentially lethal differentiation syndrome
      during all-trans retinoic acid treatment of acute promyelocytic leukemia. We
      found that such treatment not only enhanced cell-surface expression of CD11b and
      CD11c but also induced high-affinity states; atypical transglutaminase 2
      expression in NB4 cells activated the nuclear factor kappa-light-chain-enhancer
      of activated B cells pathway, driving pathogenic processes with an inflammatory
      cascade through the expression of numerous cytokines, including Tumor necrosis
      factor alpha, Interleukin 1 beta, and Monocyte chemoattractant protein 1. NC9
      decreased the amount of transglutaminase 2, p65/RelA, and p50 in differentiated
      NB4 cells and their nuclei, leading to attenuated inflammatory cytokine
      synthesis. NC9 significantly inhibits transglutaminase 2 nuclear translocation
      but accelerates its proteasomal breakdown. This study demonstrates that
      transglutaminase 2 expression induced by all-trans retinoic acid treatment
      reprograms inflammatory signaling networks governed by nuclear factor kappa-light
      chain-enhancer of activated B cells activation, resulting in over-expression of
      tumor necrosis factor alpha and Interleukin 1 beta in differentiating acute
      promyelocytic leukemia cells, suggesting that atypically expressed
      transglutaminase 2 is a promising target for leukemia treatment.

PMID- 30237269
TI  - A novel gain-of-function mutation of Piezo1 is functionally affirmed in red blood
      cells by high-throughput patch clamp.

PMID- 30237270
TI  - Somatic mosaicisms of chromosome 1 at two different stages of ontogenetic
      development detected by Rh blood group discrepancies.
AB  - Spontaneous Rh blood group changes are a striking sign, reported to occur
      preferably in patients with hematological disorders. Upon routine blood grouping,
      two unrelated individuals showed unexplained mixed red cell phenotype regarding
      the highly immunogenic c antigen (RH4) clinically relevant for blood transfusion
      and fetomaternal incompatibility. About half of their red cells were c-positive,
      whereas the other half was c-negative. These apparently hematologically healthy
      females had no history of transfusion or transplantation, and they tested
      negative for chimerism. Genotyping of flanking chromosome 1 microsatellites in
      blood, finger nails, hairs, leucocyte subpopulations and erythroid progenitor
      cells showed partial loss of heterozygosity encompassing the RHD/RHCE loci,
      spanning an 1p region of 26.7 or 42.4 Mb, respectively. Remarkably, in one case
      this was detected in all investigated tissues, whereas in the other exclusively
      myeloid cells showed loss of heterozygosity. Both carried the RhD-positive
      haplotypes CDe and the RhD-negative haplotype cde. RHD/RHCE genotypes of single
      erythroid colonies and dual-color fluorescent in-situ hybridization analyses
      indicated loss of the cde haplotype and duplication of the CDe haplotype in the
      altered cell line. Accordingly, red cell C antigen (RH2) levels of both
      propositae were higher, compared to heterozygous controls. Taken together, the
      Rhc phenotype splitting appeared to be caused by deletion of a part of 1p
      followed by duplication of homologous stretches of the sister chromosome. In one
      case, this phenomenon was confined to myeloid stem cells, while in the other a
      pluripotent stem cell line was affected, demonstrating somatic mosaicism at
      different stages of ontogenesis.

PMID- 30237271
TI  - T-cell inflamed tumor microenvironment predicts favorable prognosis in primary
      testicular lymphoma.
AB  - Primary testicular lymphoma is a rare lymphoid malignancy, most often
      representing diffuse large B-cell lymphoma histologically. Tumor microenvironment
      and limited immune surveillance have a major impact on diffuse large B-cell
      lymphoma pathogenesis and survival, but the impact on primary testicular lymphoma
      is unknown. Here, the purpose was to characterize tumor microenvironment in
      primary testicular lymphoma, and associate the findings with outcome. We profiled
      the expression of 730 immune response genes in 60 primary testicular lymphomas
      utilizing Nanostring platform, and used multiplex immunohistochemistry to
      characterize the immune cell phenotypes in the tumor tissue. We identified a gene
      signature enriched for T-lymphocyte markers differentially expressed between the
      patients. Low expression of the signature predicted poor outcome independently of
      the International Prognostic Index (progression-free survival: HR=2.810,
      CI95=1.228-6.431, p=0.014; overall survival: HR=3.267, CI95=1.406-7.590,
      p=0.006). The T-lymphocyte signature was associated with outcome also in an
      independent diffuse large B-cell lymphoma cohort (n=96). Multiplex
      immunohistochemistry revealed that poor survival of primary testicular lymphoma
      patients correlated with low percentage of CD3+CD4+ and CD3+CD8+ tumor
      infiltrating lymphocytes (p<0.001). Importantly, patients with high T-cell
      inflamed tumor microenvironment had a better response to rituximab-based
      immunochemotherapy, as compared to other patients. Furthermore, loss of membrane
      associated human-leukocyte antigen complexes was frequent and correlated with low
      T-cell infiltration. Our results demonstrate that T-cell inflamed tumor
      microenvironment associates with favorable survival in primary testicular
      lymphoma. This further highlights the importance of immune escape as a mechanism
      of treatment failure.

PMID- 30237272
TI  - Clinical and molecular features of acute promyelocytic leukemia with variant
      retinoid acid receptor fusions.

PMID- 30237273
TI  - T cell large granular lymphocytic leukemia and plasma cell disorders.

PMID- 30237274
TI  - Hypersensitivity reactions to asparaginase in mice are mediated by anti
      asparaginase IgE and IgG and the immunoglobulin receptors FcepsilonRI and
      FcgammaRIII.
AB  - Asparaginase is an important drug for the treatment of leukemias. However, anti
      asparaginase antibodies often develop, which can decrease asparaginase drug
      levels and increase the risk of relapse. The aim of this study is to identify the
      immunoglobulin isotypes and receptors responsible for asparaginase
      hypersensitivities. Mice immunized with asparaginase developed anti-asparaginase
      IgG1 and IgE antibodies, and challenging the sensitized mice with asparaginase
      induced severe hypersensitivity reactions. Flow cytometry analysis indicated that
      macrophages/monocytes, neutrophils, and basophils bind asparaginase ex vivo
      through FcgammaRIII. In contrast, asparaginase binding to basophils was dependent
      on FcgammaRIII and IgE. Consistent with the asparaginase binding data, basophil
      activation by asparaginase occurred via both IgG/FcgammaRIII and IgE/FcepsilonRI.
      Depleting >95% of B cells suppressed IgG but not IgE-dependent hypersensitivity,
      while depleting CD4+ T cells provided complete protection. Combined treatment
      with either anti-IgE mAb plus a platelet-activating factor receptor antagonist or
      anti-FcgammaRIII mAb plus a H1 receptor antagonist suppressed asparaginase
      hypersensitivity. The observations indicate that asparaginase hypersensitivity is
      mediated by antigen-specific IgG and/or IgE through the immunoglobulin receptors
      FcgammaRIII and FcepsilonRI, respectively. Provided that these results apply to
      humans, they emphasize the importance of monitoring both IgE- and IgG-mediated
      asparaginase hypersensitivities in patients receiving this agent.

PMID- 30237275
TI  - Comparison of Interfaces for the Delivery of Noninvasive Respiratory Support to
      Low Birthweight Infants.
AB  - BACKGROUND: Bench and clinical data indicate that techniques for applying
      noninvasive respiratory support may vary in terms of effectiveness, application,
      and tolerability. We implemented a new nasal interface and flow-generation system
      for the delivery of noninvasive respiratory support (NRS) to replace previously
      used systems. Our goal was to determine whether there were significant
      differences in clinically relevant outcomes between our new method and
      conventional systems. METHODS: We conducted a prospective observational study of
      preterm infants requiring noninvasive respiratory support during our initial
      implementation of a new nasal interface (RAM), and compared these data with a
      historic control group. Demographic, baseline, and clinical outcome data were
      collected. Clinical outcomes and comorbid conditions were compared by using the
      chi-square test for categorical information and the Student t test or Wilcoxon
      rank-sum test for quantitative data, depending on normality testing when using
      the Shapiro-Wilk test. Uni- and multivariate logistic regression were conducted
      to determine predictive factors for the development of bronchopulmonary
      dysplasia. RESULTS: There were no significant group differences in important
      comorbid conditions, invasive mechanical ventilation days (P = .16), or NRS
      failure within the first 7 d after birth (P = .10). Although there were no
      significant differences in the use of CPAP or noninvasive ventilation, settings
      with were significantly higher (P < .001) in the RAM group. There were more
      incidences of retinopathy of prematurity (P = .02) post RAM implementation, and
      the time to first reintubation was significantly shorter in the RAM group (P =
      .044). However, there were significant reductions post RAM in total days on any
      respiratory support (P = .009), total NRS days (P = .02), and supplemental O2
      duration (P = .02). There was a trend toward reductions in bronchopulmonary
      dysplasia rates (P = .053), and the incidence of device-related tissue breakdown
      was significantly reduced (P < .001) post RAM. Multivariate logistic regression
      results showed the type of system (odds ratio [OR] 0.19, 95% CI 0.04-0.87; P =
      .032) and total invasive ventilation time (OR 0.94, 95% CI 0.89-0.99; P = .02)
      were predictors for the development of bronchopulmonary dysplasia. CONCLUSIONS:
      The ability to apply continuous distending pressure through consistent
      application of NRS with the RAM cannula attached to a ventilator may improve
      clinical outcomes, including the duration of respiratory support and pressure
      ulcer rates. The influence of this system on the development of bronchopulmonary
      dysplasia and the significantly increased retinopathy of prematurity requires
      further study.

PMID- 30237276
TI  - Nebulized Corticosteroids in the Treatment of COPD Exacerbations: Systematic
      Review, Meta-Analysis, and Clinical Perspective.
AB  - BACKGROUND: COPD guidelines report that systemic corticosteroids are preferred
      over inhaled corticosteroids in the treatment of exacerbations, but the inhaled
      route is considered to be an option. OBJECTIVES: To conduct a systematic review
      and meta-analysis regarding the efficacy and safety of inhaled corticosteroids
      for COPD exacerbations. The second objective was to provide pharmacologic and
      clinical perspectives of inhaled corticosteroids for COPD exacerbations. METHODS:
      The primary outcome was a change in FEV1 baseline versus the last measured value.
      Secondary outcomes were a change in (PaO2 ) and (PaCO2 ) baselines versus the
      last measured values; FEV1, PaO2 , and PaCO2 at 24 or 72 h; and hyperglycemia.
      RESULTS: Each of the 9 studies included in the meta-analysis was conducted in
      subjects who were hospitalized and not critically ill. Our meta-analysis
      indicated that high-dose nebulized budesonide 4-8 mg/d was noninferior to
      systemic corticosteroids on the change in FEV1 between baseline and the last
      measured value (mean difference of 0.05, 95% CI -0.01 to 0.12, P = .13) and PaCO2
      (mean difference of -1.14, 95% CI -2.56 to 0.27, P = .11) but of inferior
      efficacy for PaO2 changes (mean difference of -1.46, 95% -2.75 to -0.16, P =
      .03). Hyperglycemia was less frequent with high-dose nebulized budesonide (risk
      ratio, 0.13; 95% CI 0.03-0.46; P = .002). CONCLUSIONS: Based on our meta-analysis
      with a change in FEV1 as the primary end point, high-dose nebulized budesonide
      was an acceptable alternative to systemic corticosteroids in hospitalized
      subjects with COPD exacerbations who were not critically ill. Additional well
      designed prospective studies are needed in both the acute care and ambulatory
      settings. We provide perspective on how this evidence might be applied in
      clinical practice.

PMID- 30237277
TI  - Reflections on the Respiratory Care Open Forum.

PMID- 30237278
TI  - Noninvasive Respiratory Support for the Premature Infant: Choosing the Optimum
      Interface.

PMID- 30237279
TI  - Breaking Down Barriers to Professional Growth.

PMID- 30237280
TI  - Mechanical Insufflation-Exsufflation: Room for Improvement.

PMID- 30237281
TI  - Editor's Commentary.

PMID- 30237282
TI  - Pandemrix vaccine: why was the public not told of early warning signs?

PMID- 30237283
TI  - Energy-dependent quenching adjusts the excitation diffusion length to regulate
      photosynthetic light harvesting.
AB  - An important determinant of crop yields is the regulation of photosystem II
      (PSII) light harvesting by energy-dependent quenching (qE). However, the
      molecular details of excitation quenching have not been quantitatively connected
      to the fraction of excitations converted to chemical energy by PSII reaction
      centers (PSII yield), which determines flux to downstream metabolism. Here, we
      incorporate excitation dissipation by qE into a pigment-scale model of excitation
      transfer and trapping for a 200 * 200-nm patch of the grana membrane. We show
      that excitation transport can be rigorously coarse grained to a 2D random walk
      with an excitation diffusion length determined by the extent of quenching. We
      present an alternative method for analyzing pulse amplitude-modulated chlorophyll
      fluorescence measurements that incorporates the effects of a variable excitation
      diffusion length during qE activation.

PMID- 30237285
TI  - Revised M06 density functional for main-group and transition-metal chemistry.
AB  - We present a hybrid metageneralized-gradient-approximation functional, revM06,
      which is based on adding Hartree-Fock exchange to the revM06-L functional form.
      Compared with the original M06 suite of density functionals, the resulting revM06
      functional has significantly improved across-the-board accuracy for both main
      group and transition-metal chemistry. The revM06 functional improves on the M06
      2X functional for main-group and transition-metal bond energies, atomic
      excitation energies, isomerization energies of large molecules, molecular
      structures, and both weakly and strongly correlated atomic and molecular data,
      and it shows a clear improvement over M06 and M06-2X for noncovalent
      interactions, including smoother potential curves for rare-gas dimers. The revM06
      functional also predicts more accurate results than M06 and M06-2X for most of
      the outside-the-training-set test sets examined in this study. Therefore, the
      revM06 functional is well-suited for a broad range of chemical applications for
      both main-group and transition-metal elements.

PMID- 30237284
TI  - Let-7i inhibition enhances progesterone-induced functional recovery in a mouse
      model of ischemia.
AB  - Progesterone (P4) is a potent neuroprotectant and a promising therapeutic for
      stroke treatment. However, the underlying mechanism(s) remain unclear. Our
      laboratory recently reported that brain-derived neurotrophic factor (BDNF) is a
      critical mediator of P4's protective actions and that P4-induced BDNF release
      from cortical astrocytes is mediated by a membrane-associated progesterone
      receptor, Pgrmc1. Here, we report that the microRNA (miRNA) let-7i is a negative
      regulator of Pgrmc1 and BDNF in glia and that let-7i disrupts P4-induced BDNF
      release and P4's beneficial effects on cell viability and markers of
      synaptogenesis. Using an in vivo model of ischemia, we demonstrate that
      inhibiting let-7i enhances P4-induced neuroprotection and facilitates functional
      recovery following stroke. The discovery of such factors that regulate the
      cytoprotective effects of P4 may lead to the development of biomarkers to
      differentiate/predict those likely to respond favorably to P4 versus those that
      do not.

PMID- 30237286
TI  - Synchronized mechanical oscillations at the cell-matrix interface in the
      formation of tensile tissue.
AB  - The formation of uniaxial fibrous tissues with defined viscoelastic properties
      implies the existence of an orchestrated mechanical interaction between the
      cytoskeleton and the extracellular matrix. This study addresses the nature of
      this interaction. The hypothesis is that this mechanical interplay underpins the
      mechanical development of the tissue. In embryonic tendon tissue, an early event
      in the development of a mechanically robust tissue is the interaction of the
      pointed tips of extracellular collagen fibrils with the fibroblast plasma
      membrane to form stable interface structures (fibripositors). Here, we used a
      fibroblast-generated tissue that is structurally and mechanically matched to
      embryonic tendon to demonstrate homeostasis of cell-derived and external strain
      derived tension over repeated cycles of strain and relaxation. A cell-derived
      oscillatory tension component is evident in this matrix construct. This
      oscillatory tension involves synchronization of individual cell forces across the
      construct and is induced in each strain cycle by transient relaxation and
      transient tensioning of the tissue. The cell-derived tension along with the
      oscillatory component is absent in the presence of blebbistatin, which disrupts
      actinomyosin force generation of the cell. The time period of this oscillation
      (60-90 s) is well-defined in each tissue sample and matches a primary
      viscoelastic relaxation time. We hypothesize that this mechanical oscillation of
      fibroblasts with plasma membrane anchored collagen fibrils is a key factor in
      mechanical sensing and feedback regulation in the formation of tensile tissues.

PMID- 30237287
TI  - Predicting polymorphism in molecular crystals using orientational entropy.
AB  - We introduce a computational method to discover polymorphs in molecular crystals
      at finite temperature. The method is based on reproducing the crystallization
      process starting from the liquid and letting the system discover the relevant
      polymorphs. This idea, however, conflicts with the fact that crystallization has
      a timescale much longer than that of molecular simulations. To bring the process
      within affordable simulation time, we enhance the fluctuations of a collective
      variable by constructing a bias potential with well-tempered metadynamics. We use
      as a collective variable an entropy surrogate based on an extended pair
      correlation function that includes the correlation between the orientations of
      pairs of molecules. We also propose a similarity metric between configurations
      based on the extended pair correlation function and a generalized Kullback
      Leibler divergence. In this way, we automatically classify the configurations as
      belonging to a given polymorph, using our metric and a hierarchical clustering
      algorithm. We apply our method to urea and naphthalene. We find different
      polymorphs for both substances, and one of them is stabilized at finite
      temperature by entropic effects.

PMID- 30237289
TI  - Role of water flow regime in the swimming behaviour and escape performance of a
      schooling fish.
AB  - Animals are exposed to variable and rapidly changing environmental flow
      conditions, such as wind in terrestrial habitats and currents in aquatic systems.
      For fishes, previous work suggests that individuals exhibit flow-induced changes
      in aerobic swimming performance. Yet, no one has examined whether similar
      plasticity is found in fast-start escape responses, which are modulated by
      anaerobic swimming performance, sensory stimuli and neural control. In this
      study, we used fish from wild schools of the tropical damselfish Chromis viridis
      from shallow reefs surrounding Lizard Island in the Great Barrier Reef,
      Australia. The flow regime at each site was measured to ascertain differences in
      mean water flow speed and its temporal variability. Swimming and escape behaviour
      in fish schools were video-recorded in a laminar-flow swim tunnel. Though each
      school's swimming behaviour (i.e. alignment and cohesion) was not associated with
      local flow conditions, traits linked with fast-start performance (particularly
      turning rate and the distance travelled with the response) were significantly
      greater in individuals from high-flow habitats. This stronger performance may
      occur due to a number of mechanisms, such as an i n s itu training effect or
      greater selection pressure for faster performance phenotypes in areas with high
      flow speed.This article has an associated First Person interview with the first
      author of the paper.

PMID- 30237288
TI  - Phevamine A, a small molecule that suppresses plant immune responses.
AB  - Bacterial plant pathogens cause significant crop damage worldwide. They invade
      plant cells by producing a variety of virulence factors, including small-molecule
      toxins and phytohormone mimics. Virulence of the model pathogen Pseudomonas
      syringae pv. tomato DC3000 (Pto) is regulated in part by the sigma factor HrpL.
      Our study of the HrpL regulon identified an uncharacterized, three-gene operon in
      Pto that is controlled by HrpL and related to the Erwinia hrp-associated systemic
      virulence (hsv) operon. Here, we demonstrate that the hsv operon contributes to
      the virulence of Pto on Arabidopsis thaliana and suppresses bacteria-induced
      immune responses. We show that the hsv-encoded enzymes in Pto synthesize a small
      molecule, phevamine A. This molecule consists of l-phenylalanine, l-valine, and a
      modified spermidine, and is different from known small molecules produced by
      phytopathogens. We show that phevamine A suppresses a potentiation effect of
      spermidine and l-arginine on the reactive oxygen species burst generated upon
      recognition of bacterial flagellin. The hsv operon is found in the genomes of
      divergent bacterial genera, including ~37% of P. syringae genomes, suggesting
      that phevamine A is a widely distributed virulence factor in phytopathogens. Our
      work identifies a small-molecule virulence factor and reveals a mechanism by
      which bacterial pathogens overcome plant defense. This work highlights the power
      of omics approaches in identifying important small molecules in bacteria-host
      interactions.

PMID- 30237290
TI  - Characterisation of maturation of photoreceptor cell subtypes during zebrafish
      retinal development.
AB  - Photoreceptor cells (PRCs) mature from simple epithelial cells, a process
      characterised by growth and compartmentalisation of the apical membrane into an
      inner and an outer segment. So far, a PRC subtype-specific description of
      morphological and cellular changes in the developing zebrafish retina is missing.
      Here, we performed an in-depth characterisation of four of the five PRC subtypes
      of the zebrafish retina between 51 and 120 h post fertilisation, including
      quantification of the size of different compartments, localisation of polarity
      proteins and positioning of organelles. One of the major findings was the
      anisotropic and subtype-specific growth of the different PRC compartments. In
      addition, a transient accumulation of endoplasmic reticulum in rod PRCs, changes
      in chromatin organisation in UV sensitive cones and differential expression of
      polarity proteins during the initial stages of PRC maturation were observed. The
      results obtained provide a developmental timeline that can be used as a platform
      for future studies on PRC maturation and function. This platform was applied to
      document that increased exposure to light leads to smaller apical domains of
      PRCs.

PMID- 30237291
TI  - Involvement of sulfated biopolymers in adhesive secretions produced by marine
      invertebrates.
AB  - Many marine invertebrates use adhesive secretions to attach to underwater
      surfaces and functional groups borne by their adhesive proteins and
      carbohydrates, such as catechols and phosphates, play a key role in adhesion. The
      occurrence of sulfates as recurrent moieties in marine bioadhesives suggests that
      they could also be involved. However, in most cases, their presence in the
      adhesive material remains speculative. We investigated the presence of sulfated
      biopolymers in five marine invertebrates representative of the four types of
      adhesion encountered in the sea: mussels and tubeworms for permanent adhesion,
      limpets for transitory adhesion, sea stars for temporary adhesion and sea
      cucumbers for instantaneous adhesion. The dry adhesive material of mussels, sea
      stars and sea cucumbers contained about 1% of sulfate. Using anti-sulfotyrosine
      antibodies and Alcian Blue staining, sulfated proteins and sulfated proteoglycans
      and/or polysaccharides were identified in the secretory cells and adhesive
      secretions of all species except the tubeworm. Sulfated proteoglycans appear to
      play a role only in the non-permanent adhesion of sea stars and limpets in which
      they could mediate cohesion within the adhesive material. In mussels and sea
      cucumbers, sulfated biopolymers would rather have an anti-adhesive function,
      precluding self-adhesion.

PMID- 30237294
TI  - Pyrexia in an older man, months after emergency.

PMID- 30237292
TI  - DARPins recognize mTFP1 as novel reagents for in vitro and in vivo protein
      manipulations.
AB  - Over the last few years, protein-based affinity reagents have proven very helpful
      in cell and developmental biology. While many of these versatile small proteins
      can be expressed both in the intracellular and extracellular milieu in cultured
      cells and in living organisms, they can also be functionalized by fusing them to
      different protein domains in order to regulate or modulate their target proteins
      in diverse manners. For example, protein binders have been employed to degrade,
      trap, localize or enzymatically modify specific target proteins. Whereas binders
      to many endogenous proteins or small protein tags have been generated, several
      affinity reagents against fluorescent proteins have also been created and used to
      manipulate target proteins tagged with the corresponding fluorescent protein.
      Both of these approaches have resulted in improved methods for cell biological
      and developmental studies. While binders against GFP and mCherry have been
      previously isolated and validated, we now report the generation and utilization
      of designed ankyrin repeat proteins (DARPins) against the monomeric teal
      fluorescent protein 1 (mTFP1). Here we use the generated DARPins to delocalize
      Rab proteins to the nuclear compartment, in which they cannot fulfil their
      regular functions anymore. In the future, such manipulations might enable the
      production of acute loss-of-function phenotypes in different cell types or in
      living organisms based on direct protein manipulation rather than on genetic loss
      of-function analyses.

PMID- 30237293
TI  - The endothelial glycocalyx anchors von Willebrand factor fibers to the vascular
      endothelium.
AB  - The dynamic change from a globular conformation to an elongated fiber determines
      the ability of von Willebrand factor (VWF) to trap platelets. Fiber formation is
      favored by the anchorage of VWF to the endothelial cell surface, and VWF-platelet
      aggregates on the endothelium contribute to inflammation, infection, and tumor
      progression. Although P-selectin and alphanubeta3-integrins may bind VWF, their
      precise role is unclear, and additional binding partners have been proposed. In
      the present study, we evaluated whether the endothelial glycocalyx anchors VWF
      fibers to the endothelium. Using microfluidic experiments, we showed that
      stabilization of the endothelial glycocalyx by chitosan oligosaccharides or
      overexpression of syndecan-1 (SDC-1) significantly supports the binding of VWF
      fibers to endothelial cells. Heparinase-mediated degradation or impaired
      synthesis of heparan sulfate (HS), a major component of the endothelial
      glycocalyx, reduces VWF fiber-dependent platelet recruitment. Molecular
      interaction studies using flow cytometry and live-cell fluorescence microscopy
      provided further evidence that VWF binds to HS linked to SDC-1. In a murine
      melanoma model, we found that protection of the endothelial glycocalyx through
      the silencing of heparanase increases the number of VWF fibers attached to the
      wall of tumor blood vessels. In conclusion, we identified HS chains as a relevant
      binding factor for VWF fibers at the endothelial cell surface in vitro and in
      vivo.

PMID- 30237296
TI  - Targeting TAZ-Driven Human Breast Cancer by Inhibiting a SKP2-p27 Signaling Axis.
AB  - Deregulated expression of the transcriptional coactivator with PDZ-binding motif
      (WWTR1/TAZ) is a common feature of basal-like breast cancer (BLBC). Yet, how
      oncogenic TAZ regulates cell-cycle progression and proliferation in breast cancer
      remains poorly understood, and whether TAZ is required for tumor maintenance has
      not been established. Here, using an integrative oncogenomic approach, TAZ
      dependent cellular programs essential for tumor growth and progression were
      identified. Significantly, TAZ-driven tumor cells required sustained TAZ
      expression, given that its withdrawal impaired both genesis and maintenance of
      solid tumors. Moreover, temporal inhibition of TAZ diminished the metastatic
      burden in established macroscopic pulmonary metastases. Mechanistic investigation
      revealed that TAZ controls distinct gene profiles that determine cancer cell fate
      through cell-cycle networks, including a specific, causal role for S-phase kinase
      associated protein 2 (SKP2) in mediating the neoplastic state. Together, this
      study elucidates the molecular events that underpin the role of TAZ in BLBC and
      link to SKP2, a convergent communication node for multiple cancer signaling
      pathways, as a key downstream effector molecule.Implications: Understanding the
      molecular role of TAZ and its link to SKP2, a signaling convergent point and key
      regulator in BLBC, represents an important step toward the identification of
      novel therapeutic targets for TAZ-dependent breast cancer. Mol Cancer Res; 1-13.
      (c)2018 AACR.

PMID- 30237295
TI  - Genomic Analysis To Identify Signatures of Artificial Selection and Loci
      Associated with Important Economic Traits in Duroc Pigs.
AB  - Identifying genetic basis of domestication and improvement in livestock
      contributes to our understanding of the role of artificial selection in shaping
      the genome. Here we used whole-genome sequencing and the genotyping by sequencing
      approach to detect artificial selection signatures and identify the associated
      SNPs of two economic traits in Duroc pigs. A total of 38 candidate selection
      regions were detected by combining the fixation index and the Composite
      Likelihood Ratio methods. Further genome-wide association study revealed seven
      associated SNPs that were related with intramuscular fat content and feed
      conversion ratio traits, respectively. Enrichment analysis suggested that the
      artificial selection regions harbored genes, such as MSTN, SOD2, MC5R and CD83,
      which are responsible for economic traits including lean muscle mass, fertility
      and immunization. Overall, this study found a series of candidate genes
      putatively associated with the breeding improvement of Duroc pigs and the
      polygenic basis of adaptive evolution, which can provide important references and
      fundamental information for future breeding programs.

PMID- 30237297
TI  - Facial Venous Malformations Are Associated with Cerebral Developmental Venous
      Anomalies.
AB  - BACKGROUND AND PURPOSE: A number of studies have demonstrated the existence of
      segmental vascular disorders affecting soft tissues of the head and neck along
      with the intracranial vasculature. The purpose of this study was to determine
      whether there is an association between cerebral developmental venous anomalies
      and venous malformations of the face, head, and neck. MATERIALS AND METHODS: A
      consecutive series of patients with head and neck venous malformations who
      underwent MR imaging of the brain with postcontrast T1- or T2*-weighted imaging
      were included. Developmental venous anomaly prevalence in this patient population
      was compared with an age- and sex-matched control group without venous
      malformations at a ratio of 1:2. All images were interpreted by 2
      neuroradiologists. Data were collected on venous malformation location,
      developmental venous anomaly location, developmental venous anomaly drainage
      pattern, and metameric location of venous malformations and developmental venous
      anomalies. Categoric variables were compared using chi2 tests. RESULTS: Forty-two
      patients with venous malformations were included. The mean age was 38.1 +/- 11.1
      years, and 78.6% of patients were female. The prevalence of developmental venous
      anomalies in this patient population was 28.6%. The control population of 84
      patients had a mean age of 40.0 +/- 5.9 years, and 78.6% of patients were female.
      The prevalence of developmental venous anomalies in this patient population was
      9.5% (P = .01). In 83.3% of cases, developmental venous anomalies were
      ipsilateral to the venous malformation, and in 75% of cases, they involved the
      same metamere. CONCLUSIONS: Our case-control study demonstrated a significant
      association between brain developmental venous anomalies and superficial venous
      malformations. These findings suggest that there may be a similar
      pathophysiologic origin for these 2 entities.

PMID- 30237298
TI  - Engorgement of Deep Medullary Veins in Neurosarcoidosis: A Common-Yet
      Underrecognized Cerebrovascular Finding on SWI.
AB  - We describe the prevalence and potential significance of deep medullary vein
      engorgement on SWI in patients with neurosarcoidosis, a finding that has not been
      described previously. Engorgement was evaluated for possible associations with
      meningeal or perivascular disease, intracranial hemorrhage, and venous
      thrombosis, as well as with modified Rankin Scale scores at the time of MR
      imaging and at follow-up. Deep medullary vein engorgement was seen in 7 of 21
      patients and was more common in men. Patients with venous engorgement had a
      significantly increased incidence of microhemorrhages, perivascular disease, and
      hydrocephalus. There was no association with the degree of leptomeningeal
      disease, venous dural sinus thrombosis, or modified Rankin Scale scores. In
      conclusion, deep medullary vein engorgement was common in our patients with
      neurosarcoidosis. Although its pathophysiology remains uncertain, it could be
      related to venous or perivenous abnormalities and may represent a useful
      secondary finding of cerebrovascular disease.

PMID- 30237299
TI  - Cerebrovascular Reactivity during Prolonged Breath-Hold in Experienced
      Freedivers.
AB  - BACKGROUND AND PURPOSE: Experienced freedivers can endure prolonged breath-holds
      despite severe hypoxemia and are therefore ideal subjects to study apnea-induced
      cerebrovascular reactivity. This multiparametric study investigated CBF, the
      spatial coefficient of variation as a correlate of arterial transit time and
      brain metabolism, dynamics during prolonged apnea. MATERIALS AND METHODS: Fifteen
      male freedivers (age range, 20-64 years; cumulative previous prolonged breath
      holds >2 minutes and 30 seconds: 4-79,200) underwent repetitive 3T
      pseudocontinuous arterial spin-labeling and 31P-/1H-MR spectroscopy before,
      during, and after a 5-minute breath-hold (split into early and late phases) and
      gave temporally matching venous blood gas samples. Correlation of temporal and
      regional cerebrovascular reactivity to blood gases and cumulative previous breath
      holds of >2 minutes and 30 seconds in a lifetime was assessed. RESULTS: The
      spatial coefficient of variation of CBF (by arterial spin-labeling) decreased
      during the early breath-hold phase (-30.0%, P = .002), whereas CBF remained
      almost stable during this phase and increased in the late phase (+51.8%, P =
      .001). CBF differed between the anterior and the posterior circulation during all
      phases (eg, during late breath-hold: MCA, 57.3 +/- 14.2 versus posterior cerebral
      artery, 42.7 +/- 10.8 mL/100 g/min; P = .001). There was an association between
      breath-hold experience and lower CBF (1000 previous breath-holds reduced WM CBF
      by 0.6 mL/100 g/min; 95% CI, 0.15-1.1 mL/100 g/min; P = .01). While breath-hold
      caused peripheral lactate rise (+18.5%) and hypoxemia (oxygen saturation, 
      24.0%), cerebral lactate and adenosine diphosphate remained within physiologic
      ranges despite early signs of oxidative stress [-6.4% phosphocreatine /
      (adenosine triphosphate + adenosine diphosphate); P = .02]. CONCLUSIONS: This
      study revealed that the cerebral energy metabolism of trained freedivers
      withstands severe hypoxic hypercarbia in prolonged breath-hold due to a complex
      cerebrovascular hemodynamic response.

PMID- 30237300
TI  - Imaging of Clival Hypoplasia in CHARGE Syndrome and Hypothesis for Development: A
      Case-Control Study.
AB  - BACKGROUND AND PURPOSE: We present the largest case series to date on basiocciput
      abnormalities in CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of
      the choanae, Retardation of growth and/or development, Genital and/or urinary
      abnormalities, and Ear abnormalities and/or deafness). We aimed to show that
      basiocciput abnormalities are common and may aid in diagnosis. We furthermore
      explored whether clivus size correlates with the type of chromodomain-helicase
      DNA binding protein 7 gene (CHD7) mutation, which causes CHARGE syndrome, and
      with clinical criteria according to Blake et al and Verloes. MATERIALS AND
      METHODS: We retrospectively analyzed the clivus of 23 patients with CHARGE
      syndrome with CHD7 mutations on MR imaging or CT. We recorded the size of the
      clivus, the Welcher angle, basilar invagination, and Chiari I malformations. We
      compared the clival size and Welcher angle of patients with CHARGE syndrome with
      those of 72 age-matched controls. Additionally, we tested for correlations
      between clivus size and mutation type or clinical criteria. RESULTS: Eighty-seven
      percent of the patients with CHARGE syndrome had an abnormal clivus; 61% had a
      clivus >2.5 SD smaller than that of age-matched controls. An abnormally large
      Welcher angle was observed in 35%. Basiocciput hypoplasia was found in 70%, and
      basilar invagination, in 29%. None of the patients had a Chiari I malformation.
      At the group level, patients with CHARGE syndrome had a smaller clivus and larger
      Welcher angle than controls. No significant correlation between clivus size and
      mutation type or clinical criteria was found. CONCLUSIONS: Most patients with
      CHARGE syndrome have an abnormal clivus. This suggests that clivus abnormalities
      may be used as an additional diagnostic tool. Our results provide evidence that
      CHD7, which is expressed in the presomitic mesoderm during somitogenesis, plays
      an important role in the formation of the clivus.

PMID- 30237301
TI  - Spinal Imaging Findings of Open Spinal Dysraphisms on Fetal and Postnatal MRI.
AB  - BACKGROUND AND PURPOSE: Fetal MRI has become a valuable tool in the evaluation of
      open spinal dysraphisms making studies comparing prenatal and postnatal MRI
      findings increasingly important. Our aim was to determine the accuracy of
      predicting the level of the spinal dysraphic defect of open spinal dysraphisms on
      fetal MR imaging and to report additional findings observed when comparing fetal
      and postnatal MR imaging of the spine in this population. MATERIALS AND METHODS:
      A single-center retrospective analysis was performed of fetal MRIs with open
      spinal dysraphisms from 2004 through 2016 with available diagnostic postnatal
      spine MR imaging. Images were reviewed by 2 board-certified fellowship-trained
      pediatric neuroradiologists. Corresponding clinical/operative reports were
      reviewed. RESULTS: One hundred nineteen fetal MRIs of open spinal dysraphisms
      were included. The level of the osseous defect between fetal and postnatal MR
      imaging was concordant in 42.9% (51/119) of cases and was 1 level different in
      39% (47/119) of cases. On postnatal MR imaging, type II split cord malformation
      was seen in 8.4% (10/119) of cases, with only 50% (5/10) of these cases
      identified prospectively on fetal MR imaging. Syrinx was noted in 3% (4/119) of
      prenatal studies, all cervical, all confirmed on postnatal MR imaging.
      CONCLUSIONS: Fetal MR imaging is accurate in detecting the level of the spinal
      dysraphic defect, which has an impact on prenatal counseling, neurologic
      outcomes, and eligibility for fetal surgery. In addition, fetal MR imaging is
      limited in its ability to detect split cord malformations in patients with open
      spinal dysraphisms. Although rare, fetal MR imaging has a high specificity for
      detection of cervical spinal cord syrinx.

PMID- 30237302
TI  - The ASNR-ACR-RSNA Common Data Elements Project: What Will It Do for the House of
      Neuroradiology?
AB  - The American Society of Neuroradiology has teamed up with the American College of
      Radiology and the Radiological Society of North America to create a catalog of
      neuroradiology common data elements that addresses specific clinical use cases.
      Fundamentally, a common data element is a question, concept, measurement, or
      feature with a set of controlled responses. This could be a measurement,
      subjective assessment, or ordinal value. Common data elements can be both machine
      and human-generated. Rather than redesigning neuroradiology reporting, the goal
      is to establish the minimum number of "essential" concepts that should be in a
      report to address a clinical question. As medicine shifts toward value-based
      service compensation methodologies, there will be an even greater need to
      benchmark quality care and allow peer-to-peer comparisons in all specialties.
      Many government programs are now focusing on these measures, the most recent
      being the Merit-Based Incentive Payment System and the Medicare Access Children's
      Health Insurance Program Reauthorization Act of 2015. Standardized or structured
      reporting is advocated as one method of assessing radiology report quality, and
      common data elements are a means for expressing these concepts. Incorporating
      common data elements into clinical practice fosters a number of very useful
      downstream processes including establishing benchmarks for quality-assurance
      programs, ensuring more accurate billing, improving communication to providers
      and patients, participating in public health initiatives, creating comparative
      effectiveness research, and providing classifiers for machine learning.
      Generalized adoption of the recommended common data elements in clinical practice
      will provide the means to collect and compare imaging report data from multiple
      institutions locally, regionally, and even nationally, to establish quality
      benchmarks.

PMID- 30237303
TI  - Dilated Vein of the Filum Terminale on MRI: A Marker for Deep Lumbar and Sacral
      Dural and Epidural Arteriovenous Fistulas.
AB  - BACKGROUND AND PURPOSE: Conventional MR imaging can provide important clues
      regarding the location of a spinal vascular malformation. We hypothesized that a
      dilated vein of the filum terminale, identified as a curvilinear flow void on
      T2WI, could be an imaging marker for a lower lumbar (L3-L5) or sacral fistula.
      MATERIALS AND METHODS: We retrospectively identified all spinal dural and spinal
      epidural arteriovenous fistulas from 2 large tertiary referral centers from 2005
      to 2018. All patients had a lumbar spinal MR imaging and a conventional spinal
      angiography. Images were reviewed by 2 neuroradiologists who categorized the
      level of the arterial feeder to the fistula and the presence or absence of a
      dilated vein of the filum terminale on T2WI and T1 postcontrast images. We
      calculated the sensitivity, specificity, positive predictive value, and negative
      predictive value of the presence of a dilated filum terminale vein for a deep
      lumbar or sacral fistula. RESULTS: One hundred sixty-two patients were included.
      An enlarged filum terminale vein was identified in 39 patients. Sensitivity,
      specificity, positive predictive value, and negative predictive value of the
      presence of a dilated filum terminale vein for a deep lumbar or sacral fistula
      were 86%, 98.3%, 94.9%, and 95.1%, respectively. CONCLUSIONS: The presence of a
      dilated vein of the filum terminale can accurately localize a spinal dural
      arteriovenous fistula/spinal epidural arteriovenous fistula to the lower lumbar
      or sacral spine in patients being evaluated for such lesions. This finding can be
      used to facilitate both noninvasive and conventional spinal angiography.

PMID- 30237304
TI  - Clinical Value of Hybrid TOF-PET/MR Imaging-Based Multiparametric Imaging in
      Localizing Seizure Focus in Patients with MRI-Negative Temporal Lobe Epilepsy.
AB  - BACKGROUND AND PURPOSE: Temporal lobe epilepsy is the most common type of
      epilepsy. Early surgical treatment is superior to prolonged medical therapy in
      refractory temporal lobe epilepsy. Successful surgical operations depend on the
      correct localization of the epileptogenic zone. This study aimed to evaluate the
      clinical value of hybrid TOF-PET/MR imaging-based multiparametric imaging in
      localizing the epileptogenic zone in patients with MR imaging-negative for
      temporal lobe epilepsy. MATERIALS AND METHODS: Twenty patients with MR imaging
      negative temporal lobe epilepsy who underwent preoperative evaluation and 10
      healthy controls were scanned using PET/MR imaging with simultaneous acquisition
      of PET and arterial spin-labeling. On the basis of the standardized uptake value
      and cerebral blood flow, receiver operating characteristic analysis and a
      logistic regression model were used to evaluate the predictive value for the
      localization. Statistical analyses were performed using statistical parametric
      mapping. The values of the standardized uptake value and cerebral blood flow, as
      well as the asymmetries of metabolism and perfusion, were compared between the 2
      groups. Histopathologic findings were used as the criterion standard. RESULTS:
      Complete concordance was noted in lateralization and localization among the PET,
      arterial spin-labeling, and histopathologic findings in 12/20 patients based on
      visual assessment. Concordance with histopathologic findings was also obtained
      for the remaining 8 patients based on the complementary PET and arterial spin
      labeling information. Receiver operating characteristic analysis showed that the
      sensitivity and specificity of PET, arterial spin-labeling, and combined PET and
      arterial spin-labeling were 100% and 81.8%, 83.3% and 54.5%, and 100% and 90.9%,
      respectively. When we compared the metabolic abnormalities in patients with those
      in healthy controls, hypometabolism was detected in the middle temporal gyrus (P
      < .001). Metabolism and perfusion asymmetries were also located in the temporal
      lobe (P < .001). CONCLUSIONS: PET/MR imaging-based multiparametric imaging
      involving arterial spin-labeling may increase the clinical value of localizing
      the epileptogenic zone by providing concordant and complementary information in
      patients with MR imaging-negative temporal lobe epilepsy.

PMID- 30237306
TI  - What is a COPD exacerbation? Current definitions, pitfalls, challenges and
      opportunities for improvement.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic illness that can be
      periodically punctuated by exacerbations, characterised by acute worsening of
      symptoms, including increased dyspnoea, cough, sputum production and sputum
      purulence. COPD exacerbations are common and have important clinical and economic
      consequences, including lost work productivity, increased utilisation of
      healthcare resources, temporary or permanent reductions in lung function and
      exercise capacity, hospitalisation, and sometimes death. Over the past two
      decades, clinicians and researchers have broadened their treatment goals for COPD
      to extend beyond improving lung function and symptoms, and have begun to address
      the importance of preventing and reducing exacerbations. However, despite the
      best efforts of clinicians and guideline committees, current definitions of COPD
      exacerbations are imperfect and fraught with problems. The cardinal symptoms of a
      COPD exacerbation are nonspecific and can result from acute cardiorespiratory
      illnesses other than COPD. A proposed definition, which may be more specific than
      current definitions, suggests that COPD exacerbation be defined as an acute or
      subacute worsening of dyspnoea (>=5 on a visual analogue scale that ranges from 0
      to 10) sometimes but not necessarily accompanied by increased cough, sputum
      volume and/or sputum purulence. Necessary laboratory criteria for an exacerbation
      include oxygen desaturation <=4% below that of stable state, elevated levels of
      circulating blood neutrophils or eosinophils (>=9000 neutrophils.mm-3 or >=2%
      blood eosinophils) and elevated C-reactive protein (>=3 mg.L-1), without evidence
      of pneumonia or pulmonary oedema on chest radiography and with negative
      laboratory test results for other aetiologies. Herein, we discuss the current
      state of the art with respect to how we define COPD exacerbations, associated
      pitfalls and challenges, and opportunities for improvement.

PMID- 30237305
TI  - Safety of biweekly alpha1-antitrypsin treatment in the RAPID programme.

PMID- 30237307
TI  - Lowering hospital walls to achieve health equity.

PMID- 30237308
TI  - ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK-AKT
      mTOR Signaling Pathway.
AB  - Breast cancer stem-like cells (BCSC) are implicated in cancer recurrence and
      metastasis of triple-negative breast cancer (TNBC). We have recently discovered
      that ganglioside GD2 expression defines BCSCs and that ST8SIA1 regulates GD2
      expression and BCSC function. In this report, we show that ST8SIA1 is highly
      expressed in primary TNBC; its expression is positively correlated with the
      expression of several BCSC-associated genes such as BCL11A, FOXC1, CXCR4,
      PDGFRbeta, SOX2, and mutations in p53. CRISPR knockout of ST8SIA1 completely
      inhibited BCSC functions, including in vitro tumorigenesis and mammosphere
      formation. Mechanistic studies discovered activation of the FAK-AKT-mTOR
      signaling pathway in GD2+ BCSCs, and its tight regulation by ST8SIA1. Finally,
      knockout of ST8SIA1 completely blocked in vivo tumor growth and metastasis by
      TNBC cells. In summary, these data demonstrate the mechanism by which ST8SIA1
      regulates tumor growth and metastasis in TNBC and identifies it as a novel
      therapeutic target.

PMID- 30237309
TI  - Tuberous sclerosis complex is required for tumor maintenance in MYC-driven
      Burkitt's lymphoma.
AB  - The tuberous sclerosis complex (TSC) 1/2 is a negative regulator of the nutrient
      sensing kinase mechanistic target of rapamycin complex (mTORC1), and its function
      is generally associated with tumor suppression. Nevertheless, biallelic loss of
      function of TSC1 or TSC2 is rarely found in malignant tumors. Here, we show that
      TSC1/2 is highly expressed in Burkitt's lymphoma cell lines and patient samples
      of human Burkitt's lymphoma, a prototypical MYC-driven cancer. Mechanistically,
      we show that MYC induces TSC1 expression by transcriptional activation of the
      TSC1 promoter and repression of miR-15a. TSC1 knockdown results in elevated
      mTORC1-dependent mitochondrial respiration enhanced ROS production and apoptosis.
      Moreover, TSC1 deficiency attenuates tumor growth in a xenograft mouse model. Our
      study reveals a novel role for TSC1 in securing homeostasis between MYC and
      mTORC1 that is required for cell survival and tumor maintenance in Burkitt's
      lymphoma. The study identifies TSC1/2 inhibition and/or mTORC1 hyperactivation as
      a novel therapeutic strategy for MYC-driven cancers.

PMID- 30237310
TI  - Buried in PEAT-discovery of a new silencing complex with opposing activities.

PMID- 30237311
TI  - Uncovering the "secret" lives of vacuolar fusion pores in living cells.

PMID- 30237314
TI  - Child awareness of and access to cigarettes: impacts of the point-of-sale display
      ban in England.
AB  - INTRODUCTION: England introduced a tobacco display ban for shops with >280 m2
      floor area ('partial ban') in 2012, then a total ban in 2015. This study assessed
      whether these were linked to child awareness of and access to cigarettes.
      METHODS: Data come from the Smoking, Drinking and Drug Use survey, an annual
      survey of children aged 11-15 years for 2010-2014 and 2016. Multivariate logistic
      regression models assessed changes in having seen cigarettes on display, usual
      sources and ease of access to cigarettes in shops RESULTS: During the partial
      display ban in 2012, 89.9% of children reported seeing cigarettes on display in
      the last year, which was reduced to 86.0% in 2016 after the total ban (adjusted
      OR 0.58, 95% CI 0.50 to 0.66). Reductions were similar in small shops (84.1% to
      79.3%)%) and supermarkets (62.6% to 57.3%)%). Although the ban was associated
      with a reduction in the proportion of regular child smokers reporting that they
      bought cigarettes in shops (57.0% in 2010 to 39.8% in 2016), we did not find
      evidence of changes in perceived difficulty or being refused sale among those who
      still did. DISCUSSION: Tobacco point-of-sale display bans in England reduced the
      exposure of children to cigarettes in shops and coincided with a decrease in
      buying cigarettes in shops. However, children do not report increased difficulty
      in obtaining cigarettes from shops, highlighting the need for additional measures
      to tackle tobacco advertising, stronger enforcement of existing laws and measures
      such as licencing for tobacco retailers.

PMID- 30237313
TI  - Conformational dynamics of the ABC transporter McjD seen by single-molecule FRET.
AB  - ABC transporters utilize ATP for export processes to provide cellular resistance
      against toxins, antibiotics, and harmful metabolites in eukaryotes and
      prokaryotes. Based on static structure snapshots, it is believed that they use an
      alternating access mechanism, which couples conformational changes to ATP binding
      (outward-open conformation) and hydrolysis (inward-open) for unidirectional
      transport driven by ATP Here, we analyzed the conformational states and dynamics
      of the antibacterial peptide exporter McjD from Escherichia coli using single
      molecule Forster resonance energy transfer (smFRET). For the first time, we
      established smFRET for an ABC exporter in a native-like lipid environment and
      directly monitor conformational dynamics in both the transmembrane- (TMD) and
      nucleotide-binding domains (NBD). With this, we unravel the ligand dependences
      that drive conformational changes in both domains. Furthermore, we observe
      intrinsic conformational dynamics in the absence of ATP and ligand in the NBDs.
      ATP binding and hydrolysis on the other hand can be observed via NBD
      conformational dynamics. We believe that the progress made here in combination
      with future studies will facilitate full understanding of ABC transport cycles.

PMID- 30237312
TI  - Syntaxin 17 regulates the localization and function of PGAM5 in mitochondrial
      division and mitophagy.
AB  - PGAM5, a mitochondrial protein phosphatase that is genetically and biochemically
      linked to PINK1, facilitates mitochondrial division by dephosphorylating the
      mitochondrial fission factor Drp1. At the onset of mitophagy, PGAM5 is cleaved by
      PARL, a rhomboid protease that degrades PINK1 in healthy cells, and the cleaved
      form facilitates the engulfment of damaged mitochondria by autophagosomes by
      dephosphorylating the mitophagy receptor FUNDC1. Here, we show that the function
      and localization of PGAM5 are regulated by syntaxin 17 (Stx17), a mitochondria
      associated membrane/mitochondria protein implicated in mitochondrial dynamics in
      fed cells and autophagy in starved cells. In healthy cells, loss of Stx17 causes
      PGAM5 aggregation within mitochondria and thereby failure of the
      dephosphorylation of Drp1, leading to mitochondrial elongation. In Parkin
      mediated mitophagy, Stx17 is prerequisite for PGAM5 to interact with FUNDC1. Our
      results reveal that the Stx17-PGAM5 axis plays pivotal roles in mitochondrial
      division and PINK1/Parkin-mediated mitophagy.

PMID- 30237315
TI  - Expected challenges of implementing universal pertussis vaccination during
      pregnancy in Quebec: a cross-sectional survey.
AB  - BACKGROUND: Vaccination of all pregnant women with an acellular pertussis
      containing vaccine (tetanus, diphtheria, pertussis [Tdap]) was recently
      recommended in Canada, ideally between 27 and 32 weeks of gestation. This study
      aimed to describe the existing model of prenatal care in Quebec and determine to
      what extent maternal vaccination against pertussis could be integrated into this
      model. METHODS: In Quebec, health care is organized around Local Community
      Service Centres (LCSCs) that serve specific geographic areas. For each of 158
      LCSCs (98.1% of LCSCs in the province), we invited 1 nurse or manager involved in
      prenatal care to participate in a cross-sectional Web-based survey. The structure
      of prenatal care visits and potential integration of maternal Tdap vaccination
      into the existing model were documented and compared according to urbanization
      level, determined with the use of census data. RESULTS: A completed survey was
      obtained for 127 LCSCs (response rate 80.4%). Only 13 (10.2%) and 14 (11.0%)
      LCSCs offered on-site visits with a nurse for the majority of pregnant women
      during the second and third trimesters, respectively. A significantly higher
      proportion of rural LCSCs than urban LCSCs offered on-site visits to pregnant
      women in the third trimester (13 [18%] v. 1 [2%]) (p = 0.003). In at least 50
      LCSC service areas (39.4%), vaccines were not available in most medical clinics
      offering prenatal care. INTERPRETATION: Given the current situation in Quebec,
      implementing universal maternal Tdap vaccination may be challenging, which may
      result in suboptimal vaccine coverage among pregnant women. As other Canadian
      provinces may face similar issues, a priority will be to evaluate province-based
      implementation models to develop efficient ways to provide maternal Tdap
      vaccination across Canada.

PMID- 30237316
TI  - The down-regulation of hsa_circ_0012919, the sponge for miR-125a-3p, contributes
      to DNA methylation of CD11a and CD70 in CD4+ T cells of systemic lupus
      erythematous.
AB  - BACKGROUND: Systemic lupus erythematous (SLE) is an autoimmune disease
      characterized by the production of autoantibodies directed against various
      autoantigens. But the expression profiles and functions of circular RNAs
      (circRNAs) in SLE are still scarce. OBJECTIVES: To explore the roles of circRNA
      in SLE and its potential diagnostic potential in SLE. METHODS: SLE patients and
      healthy control subjects were recruited. CD4+ T cells were isolated, circRNA
      microarray analysis were used to screen for circRNA candidate in CD4+ T cells.
      Expression of DNMT1, CD11a and CD70, and methylation level of CD11a and CD70 were
      detected after transfecting hsa_circ_0012919-targetted siRNA. The network
      analysis of hsa_circ_0012919 was used by bioinformatics. Luciferase reporter
      assay and fluorescence in situ hybridization (FISH) assay were used for screening
      for which miRNAs could bind with hsa_circ_0012919. RESULTS: Twelve circRNAs were
      up-regulated and two circRNAs were down-regulated in SLE patients group after
      circRNA microarray analysis. Hsa_circ_0012919 was further confirmed to be
      significantly different between healthy control and SLE patients (P<0.05) and
      associated with SLE characters (P<0.05). Down-regulation of hsa_circ_0012919 (i)
      increased the expression of DNMT1 and reduced the expression of CD70, CD11a, (ii)
      reversed the DNA hypomethylation of CD11a and CD70 in CD4+ T cells of SLE, but it
      could be reversed by down-regulation of DNMT1. Hsa_circ_0012919 regulated KLF13
      and RANTES by miR-125a Conclusion: Hsa_circ_0012919 could be regarded as a
      biomarker for SLE and hsa_circ_0012919 was the competitive endogenous RNA (ceRNA)
      for miR-125a-3p.

PMID- 30237317
TI  - Divergent early mesoderm specification underlies distinct head and trunk muscle
      programmes in vertebrates.
AB  - Head and trunk muscles have discrete embryological origins and are governed by
      distinct regulatory programmes. Whereas the developmental route of trunk muscles
      from mesoderm is well studied, that of head muscles is ill defined. Here, we show
      that, unlike the myogenic trunk paraxial mesoderm, head mesoderm development is
      independent of the T/Tbx6 network in mouse. We reveal that, in contrast to Wnt
      and FGF-driven trunk mesoderm, dual inhibition of Wnt/beta-catenin and Nodal
      specifies head mesoderm. Remarkably, the progenitors derived from embryonic stem
      cells by dual inhibition efficiently differentiate into cardiac and skeletal
      muscle cells. This twin potential is the defining feature of cardiopharyngeal
      mesoderm: the head subtype giving rise to heart and branchiomeric head muscles.
      Therefore, our findings provide compelling evidence that dual inhibition
      specifies head mesoderm and unravel the mechanism that diversifies head and trunk
      muscle programmes during early mesoderm fate commitment. Significantly, this is
      the first report of directed differentiation of pluripotent stem cells, without
      transgenes, into progenitors with muscle/heart dual potential. Ability to
      generate branchiomeric muscle in vitro could catalyse efforts in modelling
      myopathies that selectively involve head muscles.

PMID- 30237318
TI  - Patient safety and the ageing physician: a qualitative study of key stakeholder
      attitudes and experiences.
AB  - BACKGROUND: Unprecedented numbers of physicians are practicing past age 65.
      Unlike other safety-conscious industries, such as aviation, medicine lacks robust
      systems to ensure late-career physician (LCP) competence while promoting career
      longevity. OBJECTIVE: To describe the attitudes of key stakeholders about the
      oversight of LCPs and principles that might shape policy development. DESIGN:
      Thematic content analysis of interviews and focus groups. PARTICIPANTS: 40
      representatives of stakeholder groups including state medical board leaders,
      institutional chief medical officers, senior physicians (>65  years old), patient
      advocates (patients or family members in advocacy roles), nurses and junior
      physicians. Participants represented a balanced sample from all US regions,
      surgical and non-surgical specialties, and both academic and non-academic
      institutions. RESULTS: Stakeholders describe lax professional self-regulation of
      LCPs and believe this represents an important unsolved challenge. Patient safety
      and attention to physician well-being emerged as key organising principles for
      policy development. Stakeholders believe that healthcare institutions rather than
      state or certifying boards should lead implementation of policies related to
      LCPs, yet expressed concerns about resistance by physicians and the ability of
      institutions to address politically complex medical staff challenges. Respondents
      recommended a coaching and professional development framework, with environmental
      changes, to maximise safety and career longevity of physicians as they age.
      CONCLUSIONS: Key stakeholders express a desire for wider adoption of LCP
      standards, but foresee significant culture change and practical challenges ahead.
      Participants recommended that institutions lead this work, with support from
      regulatory stakeholders that endorse standards and create frameworks for policy
      adoption.

PMID- 30237319
TI  - Mice doubly deficient in Six4 and Six5 show ventral body wall defects reproducing
      human omphalocele.
AB  - Omphalocele is a human congenital anomaly in ventral body wall closure and may be
      caused by impaired formation of the primary abdominal wall (PAW) and/or defects
      in abdominal muscle development. Here, we report that mice doubly deficient in
      homeobox genes Six4 and Six5 showed the same ventral body wall closure defects as
      those seen in human omphalocele. SIX4 and SIX5 were localized in surface
      ectodermal cells and somatic mesoderm-derived mesenchymal and coelomic epithelial
      cells (CECs) in the PAW. Six4-/-;Six5-/- fetuses exhibited a large omphalocele
      with protrusion of both the liver and intestine, or a small omphalocele with
      protrusion of the intestine, with complete penetrance. The umbilical ring of Six4
      /-;Six5-/- embryos was shifted anteriorly and its lateral size was larger than
      that of normal embryos at the E11.5 stage, before the onset of myoblast migration
      into the PAW. The proliferation rates of surface ectodermal cells in the left and
      right PAW and somatic mesoderm-derived cells in the right PAW were lower in Six4
      /-;Six5-/- embryos than those of wild-type embryos at E10.5. The transition from
      CECs of the PAW to rounded mesothelial progenitor cells was impaired and the
      inner coelomic surface of the PAW was relatively smooth in Six4-/-;Six5-/-
      embryos at E11.25. Furthermore, Six4 overexpression in CECs of the PAW promoted
      ingression of CECs. Taken together, our results suggest that Six4 and Six5 are
      required for growth and morphological change of the PAW, and the impairment of
      these processes is linked to the abnormal positioning and expansion of the
      umbilical ring, which results in omphalocele.

PMID- 30237320
TI  - Changing dynamics of the drug overdose epidemic in the United States from 1979
      through 2016.
AB  - Better understanding of the dynamics of the current U.S. overdose epidemic may
      aid in the development of more effective prevention and control strategies. We
      analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital
      Statistics System in which accidental drug poisoning was identified as the main
      cause of death. By examining all available data on accidental poisoning deaths
      back to 1979 and showing that the overall 38-year curve is exponential, we
      provide evidence that the current wave of opioid overdose deaths (due to
      prescription opioids, heroin, and fentanyl) may just be the latest manifestation
      of a more fundamental longer-term process. The 38+ year smooth exponential curve
      of total U.S. annual accidental drug poisoning deaths is a composite of multiple
      distinctive subepidemics of different drugs (primarily prescription opioids,
      heroin, methadone, synthetic opioids, cocaine, and methamphetamine), each with
      its own specific demographic and geographic characteristics.

PMID- 30237321
TI  - Comment on "U-Th dating of carbonate crusts reveals Neandertal origin of Iberian
      cave art".
AB  - Hoffmann et al (Reports, 23 February 2018, p. 912) report the discovery of
      parietal art older than 64,800 years and attributed to Neanderthals, at least 25
      millennia before the oldest parietal art ever found. Instead, critical evaluation
      of their geochronological data seems to provide stronger support for an age of
      47,000 years, which is much more consistent with the archaeological background in
      hand.

PMID- 30237322
TI  - Bacterial antagonism in host-associated microbial communities.
AB  - Antagonistic interactions are abundant in microbial communities and contribute
      not only to the composition and relative proportions of their members but also to
      the longer-term stability of a community. This Review will largely focus on
      bacterial antagonism mediated by ribosomally synthesized peptides and proteins
      produced by members of host-associated microbial communities. We discuss recent
      findings on their diversity, functions, and ecological impacts. These systems
      play key roles in ecosystem defense, pathogen invasion, spatial segregation, and
      diversity but also confer indirect gains to the aggressor from products released
      by killed cells. Investigations into antagonistic bacterial interactions are
      important for our understanding of how the microbiota establish within hosts,
      influence health and disease, and offer insights into potential translational
      applications.

PMID- 30237323
TI  - Erratum for the Report "Precursors of logical reasoning in preverbal human
      infants" by N. Cesana-Arlotti, A. Martin, E. Teglas, L. Vorobyova, R. Cetnarski,
      L. L. Bonatti.

PMID- 30237324
TI  - The periodic coloration in birds forms through a prepattern of somite origin.
AB  - The periodic stripes and spots that often adorn animals' coats have been largely
      viewed as self-organizing patterns, forming through dynamics such as Turing's
      reaction-diffusion within the developing skin. Whether preexisting positional
      information also contributes to the periodicity and orientation of these patterns
      has, however, remained unclear. We used natural variation in colored stripes of
      juvenile galliform birds to show that stripes form in a two-step process.
      Autonomous signaling from the somite sets stripe position by forming a composite
      prepattern marked by the expression profile of agouti Subsequently, agouti
      regulates stripe width through dose-dependent control of local pigment
      production. These results reveal that early developmental landmarks can shape
      periodic patterns upstream of late local dynamics, and thus constrain their
      evolution.

PMID- 30237325
TI  - A gut-brain neural circuit for nutrient sensory transduction.
AB  - The brain is thought to sense gut stimuli only via the passive release of
      hormones. This is because no connection has been described between the vagus and
      the putative gut epithelial sensor cell-the enteroendocrine cell. However, these
      electrically excitable cells contain several features of epithelial transducers.
      Using a mouse model, we found that enteroendocrine cells synapse with vagal
      neurons to transduce gut luminal signals in milliseconds by using glutamate as a
      neurotransmitter. These synaptically connected enteroendocrine cells are referred
      to henceforth as neuropod cells. The neuroepithelial circuit they form connects
      the intestinal lumen to the brainstem in one synapse, opening a physical conduit
      for the brain to sense gut stimuli with the temporal precision and topographical
      resolution of a synapse.

PMID- 30237326
TI  - Challenges for commercializing perovskite solar cells.
AB  - Perovskite solar cells (PSCs) have witnessed rapidly rising power conversion
      efficiencies, together with advances in stability and upscaling. Despite these
      advances, their limited stability and need to prove upscaling remain crucial
      hurdles on the path to commercialization. We summarize recent advances toward
      commercially viable PSCs and discuss challenges that remain. We expound the
      development of standardized protocols to distinguish intrinsic and extrinsic
      degradation factors in perovskites. We review accelerated aging tests in both
      cells and modules and discuss the prediction of lifetimes on the basis of
      degradation kinetics. Mature photovoltaic solutions, which have demonstrated
      excellent long-term stability in field applications, offer the perovskite
      community valuable insights into clearing the hurdles to commercialization.

PMID- 30237327
TI  - Cellular checkpoint control using programmable sequential logic.
AB  - Biological processes that require orderly progression, such as growth and
      differentiation, proceed via regulatory checkpoints where the cell waits for
      signals before continuing to the next state. Implementing such control would
      allow genetic engineers to divide complex tasks into stages. We present genetic
      circuits that encode sequential logic to instruct Escherichia coli to proceed
      through a linear or cyclical sequence of states. These are built with 11 set
      reset latches, designed with repressor-based NOR gates, which can connect to each
      other and sensors. The performance of circuits with up to three latches and four
      sensors, including a gated D latch, closely match predictions made by using
      nonlinear dynamics. Checkpoint control is demonstrated by switching cells between
      multiple circuit states in response to external signals over days.

PMID- 30237328
TI  - Address harassment now.

PMID- 30237329
TI  - News at a glance.

PMID- 30237330
TI  - Deadly storms break records, damage facilities.

PMID- 30237331
TI  - Evidence-based medicine group expels internal critic.

PMID- 30237332
TI  - Drug pair shows promise for treating sleep apnea.

PMID- 30237333
TI  - AAAS adopts new policy for ejecting harassers.

PMID- 30237334
TI  - A modular backbone aided the rise of mammals.

PMID- 30237335
TI  - Brain scientists dive into deep neural networks.

PMID- 30237336
TI  - Research on research.

PMID- 30237337
TI  - Journals under the microscope.

PMID- 30237338
TI  - The metawars.

PMID- 30237340
TI  - A recipe for rigor.

PMID- 30237339
TI  - The truth squad.

PMID- 30237342
TI  - Chemical clues to the earliest animal fossils.

PMID- 30237343
TI  - Programming cells and tissues.

PMID- 30237341
TI  - Toward a more scientific science.

PMID- 30237344
TI  - Fighting chaos with chaos in lasers.

PMID- 30237345
TI  - A bird's inner stripes.

PMID- 30237346
TI  - A gut feeling.

PMID- 30237347
TI  - Bang or whimper?

PMID- 30237348
TI  - Pollution threatens toothed whales.

PMID- 30237349
TI  - Good governance for migratory species.

PMID- 30237350
TI  - Science outreach in the Borneo jungle.

PMID- 30237351
TI  - Reconfigurable system for automated optimization of diverse chemical reactions.
AB  - Chemical synthesis generally requires labor-intensive, sometimes tedious trial
      and-error optimization of reaction conditions. Here, we describe a plug-and-play,
      continuous-flow chemical synthesis system that mitigates this challenge with an
      integrated combination of hardware, software, and analytics. The system software
      controls the user-selected reagents and unit operations (reactors and
      separators), processes reaction analytics (high-performance liquid
      chromatography, mass spectrometry, vibrational spectroscopy), and conducts
      automated optimizations. The capabilities of this system are demonstrated in high
      yielding implementations of C-C and C-N cross-coupling, olefination, reductive
      amination, nucleophilic aromatic substitution (SNAr), photoredox catalysis, and a
      multistep sequence. The graphical user interface enables users to initiate
      optimizations, monitor progress remotely, and analyze results. Subsequent users
      of an optimized procedure need only download an electronic file, comparable to a
      smartphone application, to implement the protocol on their own apparatus.

PMID- 30237352
TI  - Asteroseismic detection of latitudinal differential rotation in 13 Sun-like
      stars.
AB  - The differentially rotating outer layers of stars are thought to play a role in
      driving their magnetic activity, but the underlying mechanisms that generate and
      sustain differential rotation are poorly understood. We report the measurement
      using asteroseismology of latitudinal differential rotation in the convection
      zones of 40 Sun-like stars. For the most significant detections, the stars'
      equators rotate approximately twice as fast as their midlatitudes. The
      latitudinal shear inferred from asteroseismology is much larger than predictions
      from numerical simulations.

PMID- 30237353
TI  - Measurement of a superconducting qubit with a microwave photon counter.
AB  - Fast, high-fidelity measurement is a key ingredient for quantum error correction.
      Conventional approaches to the measurement of superconducting qubits, involving
      linear amplification of a microwave probe tone followed by heterodyne detection
      at room temperature, do not scale well to large system sizes. We introduce an
      approach to measurement based on a microwave photon counter demonstrating raw
      single-shot measurement fidelity of 92%. Moreover, the intrinsic damping of the
      photon counter is used to extract the energy released by the measurement process,
      allowing repeated high-fidelity quantum nondemolition measurements. Our scheme
      provides access to the classical outcome of projective quantum measurement at the
      millikelvin stage and could form the basis for a scalable quantum-to-classical
      interface.

PMID- 30237354
TI  - Self-assembly of lattices with high structural complexity from a geometrically
      simple molecule.
AB  - Here we report an anomalous porous molecular crystal built of C-H...N-bonded
      double-layered roof-floor components and wall components of a segregatively
      interdigitated architecture. This complicated porous structure consists of only
      one type of fully aromatic multijoint molecule carrying three identical
      dipyridylphenyl wedges. Despite its high symmetry, this molecule accomplishes
      difficult tasks by using two of its three wedges for roof-floor formation and
      using its other wedge for wall formation. Although a C-H...N bond is extremely
      labile, the porous crystal maintains its porosity until thermal breakdown of the
      C-H...N bonds at 202 degrees C occurs, affording a nonporous polymorph. Though
      this nonporous crystal survives even at 325 degrees C, it can retrieve the parent
      porosity under acetonitrile vapor. These findings show how one can translate
      simplicity into ultrahigh complexity.

PMID- 30237356
TI  - Fossils reveal the complex evolutionary history of the mammalian regionalized
      spine.
AB  - A unique characteristic of mammals is a vertebral column with anatomically
      distinct regions, but when and how this trait evolved remains unknown. We
      reconstructed vertebral regions and their morphological disparity in the extinct
      forerunners of mammals, the nonmammalian synapsids, to elucidate the evolution of
      mammalian axial differentiation. Mapping patterns of regionalization and
      disparity (heterogeneity) across amniotes reveals that both traits increased
      during synapsid evolution. However, the onset of regionalization predates
      increased heterogeneity. On the basis of inferred homology patterns, we propose a
      "pectoral-first" hypothesis for region acquisition, whereby evolutionary shifts
      in forelimb function in nonmammalian therapsids drove increasing vertebral
      modularity prior to differentiation of the vertebral column for specialized
      functions in mammals.

PMID- 30237355
TI  - Ancient steroids establish the Ediacaran fossil Dickinsonia as one of the
      earliest animals.
AB  - The enigmatic Ediacara biota (571 million to 541 million years ago) represents
      the first macroscopic complex organisms in the geological record and may hold the
      key to our understanding of the origin of animals. Ediacaran macrofossils are as
      "strange as life on another planet" and have evaded taxonomic classification,
      with interpretations ranging from marine animals or giant single-celled protists
      to terrestrial lichens. Here, we show that lipid biomarkers extracted from
      organically preserved Ediacaran macrofossils unambiguously clarify their
      phylogeny. Dickinsonia and its relatives solely produced cholesteroids, a
      hallmark of animals. Our results make these iconic members of the Ediacara biota
      the oldest confirmed macroscopic animals in the rock record, indicating that the
      appearance of the Ediacara biota was indeed a prelude to the Cambrian explosion
      of animal life.

PMID- 30237357
TI  - Programmable protein circuits in living cells.
AB  - Synthetic protein-level circuits could enable engineering of powerful new
      cellular behaviors. Rational protein circuit design would be facilitated by a
      composable protein-protein regulation system in which individual protein
      components can regulate one another to create a variety of different circuit
      architectures. In this study, we show that engineered viral proteases can
      function as composable protein components, which can together implement a broad
      variety of circuit-level functions in mammalian cells. In this system, termed
      CHOMP (circuits of hacked orthogonal modular proteases), input proteases dock
      with and cleave target proteases to inhibit their function. These components can
      be connected to generate regulatory cascades, binary logic gates, and dynamic
      analog signal-processing functions. To demonstrate the utility of this system, we
      rationally designed a circuit that induces cell death in response to upstream
      activators of the Ras oncogene. Because CHOMP circuits can perform complex
      functions yet be encoded as single transcripts and delivered without genomic
      integration, they offer a scalable platform to facilitate protein circuit
      engineering for biotechnological applications.

PMID- 30237358
TI  - Afraid to fail? Reach out.

PMID- 30237359
TI  - [The Roles of Designated Core Hospitals and Cooperative Hospitals for Cancer
      Genomic Medicine in Japan].
AB  - The frameworks providing cancer genome medicine in the real world have been
      implemented under the government initiatives. In April 2018, 11 Designated Core
      Hospitals for Cancer Genomic Medicine and 100 Cooperative Hospitals for Cancer
      Genomic Medicine were designated. In the Cooperative Hospitals, the specimens may
      be submitted to the genetic testing after informed consent from cancer patients
      who wishes to have cancer genome medicine. On completion of the genetic testing,
      attending physicians should participate in the expert panel held at the
      Designated Core Hospitals to decide the recommended treatment, which may be done
      under patients' consent. The Designated Core Hospitals, in addition, are required
      to conduct multiple-gene panel testing(outsourcing is acceptable), to hold the
      regular expert panel to decide the recommended treatment based on annotation
      information, to mainly conduct investigator-initiated clinical trial and advanced
      medical care B, to nurture specialized human resources involved in cancer genome
      medicine, and to provide clinical support for the Cooperative Hospitals to
      conduct cancer genome medicine when necessary. Genomic and clinical information
      may be centralized from these hospitals and institutes to the Center for Cancer
      genomics and Advanced Therapeutics(C-CAT)to develop new knowledge databases of
      Japanese cancer patients as well as to develop brand new medicines in future.

PMID- 30237360
TI  - [The Pedigree of Immuno-Oncology - History and Current Status of Immunotherapy
      against Malignancy].
AB  - Since 1970s immunotherapy had been thought to be one of feasible strategies
      against malignancy. During that time nonspecific immunotherapy by biological
      response modifiers(BRMs), peptide vaccine therapy, dendritic cell-based vaccine
      therapy, adoptive cell therapy, targeting therapy by use of monoclonal antibody,
      and so on, had been investigated but finally they resulted in disappointment
      because of inappropriate clinical trials followed by limited efficacy. Therefore
      the understanding of clinical oncologists in regard to immunotherapy had been
      considerably poor until 2010. Nevertheless the steady efforts had made a progress
      in immunotherapy against malignancy, especially in the field of immunological
      targeting therapy by use of monoclonal antibodies related to immune checkpoint
      pathway. Even though there are plenty of problems to be resolved especially in
      terms of biomarker, the blockade of the immune checkpoint pathway could be
      effective in many patients with a variety of advanced malignant tumors, and in
      some cases inducing durable remissions. There is no longer any doubt that the
      immune system does work in tumor eradication. Nowadays immunotherapy has come of
      age and the same as surgical resection, chemotherapy and radiotherapy,
      immunotherapy could hold an important position in the field of strategies against
      malignancy.

PMID- 30237361
TI  - [A Study of Biomarkers in Immuno-Oncology - Correlation between Gut Microbiome
      Composition and the Effects of Immune Checkpoint Inhibitors].
AB  - Currently, anti-PD-1 inhibitors(nivolumab and pembrolizumab)are used for patients
      with non-small cell lung cancer (NSCLC), although the role of this biomarker is
      not yet fully characterized. PD-L1 expression in the tumor has been established
      as a biomarker of the effects of pembrolizumab; however, a number of PD-L1
      negative patients have benefited from nivolumab or other immune checkpoint
      inhibitors, suggesting that there might be additional relevant biomarkers.
      Notably, tumor mutation burden or tumor infiltrating lymphocytes might be useful
      biomarkers for these patients; the gut microbiome has received similar attention.
      It has been reported that mouse models of melanoma with certain types of
      microbiomes benefit from the use of immune checkpoint inhibitors. Even in human
      cases, those with certain types of microbiomes tended to benefit from immune
      checkpoint inhibitor treatment and exhibited elevated CD8-positive T cell counts.
      Additionally, when combined with antibiotics, the effect of the anti-PD-1
      antibody was attenuated; conversely, mice that were treated with certain species
      of bacteria experienced beneficial outcomes from anti-PD-1 antibody treatment.
      This suggested that manipulation of the gut microbiome might alter treatment
      effects. Here, we analyzed the microbiome of 12 patients with advanced or
      recurrent NSCLC who were treated with anti-PD-1 antibody. There was no major
      difference between before and after administration in microbiome of each case.
      Cluster analysis indicated no significant differences in oral microbiomes among
      the patients before the administration of the anti-PD-1 antibody. Comparative
      analysis of the patients' gut microbiomes is ongoing. We plan to continue further
      examination to reveal whether the intestinal environment influences the
      effectiveness of immune checkpoint inhibitors in NSCLC patients.

PMID- 30237362
TI  - [Translational Research in Immuno-Oncology - Comprehensive Analysis of Phenotypes
      and Functions of Various Immune Cells Using the Colorectal Cancer Surgical
      Sample].
AB  - Colorectal cancer(CRC)is one of the increasing cancers, and development of novel
      treatments is imperative for advanced CRC. In recent years, immune checkpoint
      inhibitors have demonstrated impressive clinical efficacy in various types of
      cancers, but only limited clinical responses were reported in CRC. It has been
      reported that such poor therapeutic effects might be possibly due to immune
      suppressive mechanisms other than immune checkpoints in the CRC. Therefore,
      comprehensive grasp of the immune environment is considered to be of significance
      for CRC patients. Our study aims to comprehensively assess the phenotypes and
      functions of various immune cells isolated from various tissues, including
      primary tumors and related lymph nodes, in primary CRC patients. Our preliminary
      results by flow cytometry analysis suggest that the immune suppression,
      particularly in regional lymph nodes, may be related to tumor progression.
      Further studies remain to be performed to more thoroughly elucidate immune
      suppressive mechanisms, and thereby to develop a novel immunotherapeutic strategy
      in the CRC.

PMID- 30237363
TI  - [Upper G. I. Cancer].

PMID- 30237364
TI  - [I. Immunotherapy for Esophageal Cancer].

PMID- 30237365
TI  - [II. Treatment Strategy for Esophagogastric Junction Tumor].

PMID- 30237366
TI  - [III. Conversion Therapy for Gastric Cancer].

PMID- 30237367
TI  - [A Multi-Stakeholder Dialogue on Universal Health Coverage for Cancer in Asia -
      Seeking an Approach to Asia Health and Wellbeing Initiative].
AB  - UICC-Asia Regional Office(UICC-ARO)successfully convened a fruitful Multi
      stakeholder Dialogue at United Nations University in Aoyama, Tokyo, which brought
      together parliamentarians, representatives ofthe WHO and Japanese government
      agencies and NGOs, senior executives ofpharmaceutical and other companies, and
      leading members ofJapan 's cancer research community. This meeting provided a
      valuable opportunity for stakeholders from all sectors of society to discuss ways
      in which Japan can develop a multi-sectoral approach that will promote access to
      cancer care and support initiatives for UHC for cancer in Asia. UICC-ARO Director
      Hideyuki Akaza and Haruhiko Hirate(Chair of International Affairs Committee,
      JPMA) co-chaired the meeting. At the outset it was noted that with cancer now
      firmly on the global health agenda with the adoption ofthe WHA Cancer Resolution,
      countries around the world are coming to grips with the necessity for concerted
      and cooperative action on cancer prevention and control. This dialogue marks the
      first step in efforts to pool resources and information, and noted that with
      various key international meetings due to be held in 2018 and 2019, now was the
      time to coalesce opinions and identify a concrete direction for action.

PMID- 30237368
TI  - [The Elucidation of Tumor Immunosuppression Affected by Cancer-Associated
      Fibroblasts].
AB  - Development of immunotherapy, especially checkpoint inhibitors, dramatically
      improved the prognosis of some malignancies. However, problems on the occurrence
      of severe adverse effects and limited responses to these checkpoint inhibitors
      remain. Recently, tumor infiltrating lymphocytes(TILs)are the predictive markers
      of immunotherapies based on clinical evidence. The proportion of cytotoxic T
      cells in the tumor has been reported to affect the antitumor effect. TILs in the
      tumor are thought to be controlled by the interaction between cancer and tumor
      microenvironment. As a cause of tumor immunosuppression, cancer-associated
      fibroblasts(CAFs)play the main role in the tumor microenvironment. We considered
      the strong involvement of tumor microenvironment, particularly the role of CAFs,
      and reported the interaction between CAFs and proliferation, invasion,
      angiogenesis, and resistance in the conventional therapy. The correlation between
      CAFs and tumor immunity and the immunosuppression promoted by CAFs were also
      evaluated. Their effects will be reported in our future studies.

PMID- 30237369
TI  - [A Retrospective Analysis on Comparative Treatment Results for Breast Cancer
      between Elderly Women Aged 70 and More Than 80 Years].
AB  - This study compared the treatment results of over 80-year-old(O-80) 54 and 157
      septuagenarian(70s)women with breast cancer(BC)from 1996 to 2015, to clarify the
      best treatment option for O-80BC patients. No differences were observed in the
      stages and subtypes. More than 70% of women in both groups underwent breast
      conserving surgery(BCS), and 48.1% and 12.1% of O-80BC and 70sBC patients did not
      undergo axillary dissection, respectively. About 3.2% and 18.5% of 70sBC and O
      80BC patients did not receive adjuvant therapies, respectively. Most ER-positive
      patients in both groups received endocrine therapy. Most patients in both groups
      received no intravenous chemotherapy; however, oral chemotherapy was administered
      in 80.3% of 70sBC and 64.8% of O-80BC patients. Approximately 75.2% of 70sBC and
      11.1% of O-80BC patients received post-surgical radiotherapy(RT). No differences
      in both relapse-free survival and overall survival (OS)rates were observed
      between the 2 groups. Breast cancer-related death(57.1%)and natural death from
      old age (57.1%)were the most commonly observed cause of death in the 70sBC and O
      80BC groups, respectively. Multivariate analyses on OS demonstrated that BCS and
      intravenous chemotherapy were significantly associated with poor prognosis and RT
      was significantly associated with better prognosis in 70sBC group, whereas BCS
      was significantly associated with better prognosis in O-80BC group. In
      conclusion, surgery, especially BCS, plays an important role in the primary
      treatment of O- 80BC patients; however, axillary dissection, RT, endocrine
      therapy, and chemotherapy cannot be performed.

PMID- 30237370
TI  - [Is Balloon-Occluded Transcatheter Arterial Chemoembolization Effective in
      Patients with Hepatocellular Carcinoma That Is Unresponsive to Conventional
      Transcatheter Arterial Chemoembolization ?]
AB  - We previously reported that the antitumor response of balloon-occluded
      transcatheter arterial chemoembolization(BTACE) is better than that of
      conventional transcatheter arterial chemoembolization(C-TACE). Thus far, little
      attention has been paid on the efficacy of B-TACE using the same antitumor agents
      for hepatocellular carcinoma(HCC)that is unresponsive to C-TACE, which is defined
      as C50% necrosis of the targeted nodules or the appearance of new lesions in the
      liver 1-3 months following one C-TACE procedure. Therefore, this study focused on
      the efficacy of B-TACE using the same antitumor agents for HCC that is
      unresponsive to C-TACE. Fourteen patients treated with B-TACE at our institution
      were retrospectively investigated between January 2011 and August 2015. The
      median age was 76(interquartile range[IQR]70-79)years, and 9 patients(64.3%)were
      men. A total of 9(64.3%)and 5(35.7%)patients had the Child-Pugh class A and B,
      respectively. The median maximum tumor diameter was 30(IQR 18-40)mm, and
      4(28.6%), 3(21.4%), 0(0.0%), and 7(50.0%) patients had 1, 2, 3, andB4 tumors,
      respectively. The antitumor effects were CR, PR, SD, and PD in 6(42.9%), 1(7.1%),
      3 (21.4%), and 7(28.6%)patients, respectively. The response and disease control
      rates were 50% and 71.4%, respectively. Our results suggest that B-TACE is an
      effective modality for the treatment of HCC that is unresponsive to C-TACE.

PMID- 30237371
TI  - [Regorafenib and Trifluridine and Tipiracil Hydrochloride Can Potentially Improve
      the Survival Time for Patients with Advanced or Recurrent Colorectal Cancer].
AB  - Regorafenib and trifluridine and tipiracil hydrochloride(TFTD)have been recently
      used for the treatment of advanced or recurrent colorectal cancer during or after
      the third-line therapy. These drugs are expected to prolong survival. The
      progression- free survival period associated with each drug in clinical trials is
      known to be less than 2 months. However, reports on the overall survival in the
      sequential therapy with these drugs have been limited. In our institution,
      sequential therapy using regorafenib and TFTD has achieved longer median survival
      time(MST)than the previously reported. The MST with monotherapy and sequential
      therapy was 37 and 45 months, respectively. We currently have a patient who has
      not had cancer progression for 3 years and 6 months with monotherapy. Regorafenib
      and TFTD can potentially improve the survival time beyond our observations on
      monotherapy when used at the appropriate time and with a thorough understanding
      of their adverse effects.

PMID- 30237372
TI  - [Efficacy and Safety of Carboplatin/Nanoparticle Albumin-Bound Paclitaxel
      Combination Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer or
      Recurrent Non-Small-Cell Lung Cancer Following Surgery].
AB  - OBJECTIVE: A retrospective analysis on carboplatin(CBDCA)/nanoparticle albumin
      boundpaclitaxel(nab-PTX)combination chemotherapy was conducted in patients with
      non-small-cell lung cancer(NSCLC)to evaluate both the efficacy and toxicity based
      on age, treatment line, histology, and underlying diseases. SUBJECTS: A total of
      27 patients with advanced or recurrent NSCLC following surgery who receivedCBDCA
      /nab-PTX as first- andsecond -line combination chemotherapy, respectively, were
      investigatedfrom March 2013 to December 2015. RESULTS: The overall response rate,
      median progressionfree survival, andmed ian overall survival of all patients were
      37.0%, 5.5 months, and 11.4 months, respectively. With regard to toxicity,
      3.7%and 14.8%of all patients had peripheral disorder and interstitial lung
      disease(ILD), respectively. Treatmentrelatedd eaths were not observed. No
      difference in the efficacy basedon age, treatment line, histology, andund erlying
      diseases was observed. CONCLUSION: CBDCA/nab-PTX combination chemotherapy was
      safe for elderly patients and those with ILD. However, the occurrence of new
      interstitial lung lesions should be carefully considered.

PMID- 30237373
TI  - [Situation and Problems of Cancer Treatment Support Centers at Designated Cancer
      Hospitals of the 2016 Kumamoto Earthquake].
AB  - The 2016 Kumamoto earthquake occurred while the cancer consultation support
      center was being developed at each designated cancer hospital under the second
      Basic Plan to Promote Cancer Control Programs. After the earthquake, an
      earthquake investigation team was organized that consisted of the representatives
      of several medical institutions and researched the cancer support system of every
      cancer-related institution. Many problems in the cancer consultation supporting
      system became apparent. In large-scale disasters, the role of the cancer
      consultation support center is large, and it is important to improve information
      collaboration and the consultation support system adapted to the area.

PMID- 30237374
TI  - [The Situation and Problems of Cancer Treatment at Designated Cancer Hospitals
      during the 2016 Kumamoto Earthquake].
AB  - The 2016 Kumamoto earthquake was the first disaster we experienced while pushing
      cancer medical collaboration systems under the second Basic Plan to Promote
      Cancer Control Programs.Soon after the earthquake, an earthquake investigation
      team comprising the representatives of several medical institutions was formed,
      and they performed a survey of the medical staff of every designated cancer
      hospital and other related institution.The importance of sharing information
      during disasters and the weaknesses of medical aspects and patients were
      clarified.We found it important to establish regional cooperation and a solid
      communication system during a disaster.For large-scale disasters, it is necessary
      to develop an informationsharing system that meets regional needs.

PMID- 30237375
TI  - [A Survey to Compare the Specifications and Stability of Anticancer Drugs in
      Japan, the United States, Canada, and Australia].
AB  - Recently, expensive anticancer drugs such as molecularly targeted drugs have been
      reportedly ineffective. The use of drug vial optimization(DVO)has been proposed
      to overcome this problem. The specifications and stability of anticancer drugs in
      Japan were compared to those in other countries that used DVO, based on the
      results of the survey reported at the 2016 International Society of Oncology
      Pharmacy Practitioners meeting that compared the international specifications and
      stability of anticancer drugs. Our survey investigated expensive and frequently
      used anticancer drugs: 14 anticancer monoclonal anti- bodies(MABs)and 26
      cytotoxic agents. About 29%(4/14)of the MABs and 54%(14/26)of the cytotoxic
      agents mar- keted in other countries were sold in larger vials than those
      marketed in Japan. About 67%(2/3)of theMABs and 38%(8/ 21)of the cytotoxic agents
      marketed in other countries had stability data of reconstitution obtained across
      longer test periods than those in Japan. About 29%(4/14)of theMABs and
      50%(13/26)of the cytotoxic agents marketed in other countries had stability data
      of final dilution obtained across longer test periods than those in Japan. The
      stability data obtained in Japan were comparable to those obtained in 3 other
      countries that used DVO. However, some differences were noted in the
      specifications of anticancer drugs between Japan and other countries.

PMID- 30237376
TI  - [A Case of Mediastinal Small Cell Lung Cancer in a Patient Receiving Mechanical
      Ventilation Who Was Successfully Treated with Chemotherapy and Finally
      Extubated].
AB  - BACKGROUND: The efficacy and safety of chemotherapy for patients with lung cancer
      who are in need of intensive care, such as invasive mechanical ventilation, have
      not been established. CASE: A 59-year-old woman consulted a doctor with
      complaints of dyspnea.She was intubated because of acute respiratory failure and
      transferred to our hospital.Enhanced CT images revealed advanced stenosis of her
      trachea due to a bulky mediastinal tumor.Cervical lymph node biopsy was
      performed, and she was diagnosed with mediastinal small cell lung cancer.She
      received combination chemotherapy with carboplatin and etoposide along with
      invasive mechanical ventilation.Chemotherapy was effective, and extubation was
      performed under careful bronchoscopic observation.Her general condition improved
      gradually, and she was discharged from our hospital on foot with ambulatory
      chemotherapy. CONCLUSION: Even though patients with lung cancer develop
      respiratory failure and need invasive mechanical ventilation, they may be treated
      with effective chemotherapy and may be weaned from ventilation.

PMID- 30237377
TI  - [Successful Hepatic Arterial Injection Chemotherapy for Hepatocellular Carcinoma
      with Inferior Vena Cava Invasion and Extrahepatic Spread in a Patient with Child
      Pugh Class BLiver Cirrhosis].
AB  - A 65-year-old woman who had liver cirrhosis(Child-Pugh class B)due to hepatitis C
      infection was diagnosed with hepatocellular carcinoma with hepatic vein invasion,
      portal vein tumor invasion, and lung metastasis. No recommended treatment was
      noted in the clinical practice guidelines for hepatocellular carcinoma with
      vascular invasion in patients with Child- Pugh class B liver cirrhosis. After
      initiating arterial injection chemotherapy, marked decreases in tumor size of
      lung metastasis, vascular invasion, and primary liver cancer were observed. Based
      on our experience and previous reports, hepatic arterial infusion chemotherapy
      was considered valuable for hepatocellular carcinoma with vascular invasion, even
      in patients with Child-Pugh class B liver cirrhosis.

PMID- 30237378
TI  - [A Case of Triple Negative Breast Cancer Successfully Treated with S-1].
AB  - A 73-year-old woman noticed a mass in her right breast about 1 year ago and
      consulted our hospital for an enlarged mass of about 10 cm in diameter.She was
      diagnosed with locally advanced triple negative breast cancer, and we initiated S
      1 treatment as neoadjuvant chemotherapy.After 4 chemotherapy courses, computed
      tomography showed that the primary tumor had shrunk.Therefore, right mastectomy
      and axillary dissection were performed, and UFT was administered after
      surgery.She is currently alive with no recurrence 18 months after surgery.

PMID- 30237379
TI  - [A Treatment Strategy against Double Presentation of Breast Cancer and Malignant
      Lymphoma].
AB  - Case 1 involved a 75-year-old woman with breast cancer and diffuse large B-cell
      lymphoma(DLBCL).Although we initially administered the R-CHOP regimen, the breast
      tumor increased in size and surgery had to be performed.After surgery, the R-CHOP
      regimen was re-initiated and DLBCL achieved clinical complete response.Case 2
      involved a 74-year-old woman with breast cancer and gastric MALT lymphoma.After
      administration of rituximab and H. pylori eradication, a therapeutic effect was
      achieved in the lymphoma.A docetaxel and FEC regimen was continuously
      administered and surgery was performed. Case 3 involved a 62-year-old woman with
      breast cancer and follicular lymphoma.She presented with a history of DLBCL
      treatment.We performed mastectomy and sentinel lymph node biopsy, which revealed
      metastasis of breast cancer, and axillary lymph node dissection was subsequently
      performed.Considering the pathological stage, adjuvant chemotherapy was needed.We
      selected the TCH regimen based on her past treatment.In conclusion, it is
      necessary to treat patients with double presentation of breast cancer and
      malignant lymphoma through cooperation with different departments.

PMID- 30237380
TI  - [A Case of Granulocyte-Colony Stimulating Factor Producing Esophageal Carcinoma].
AB  - The patient was a 42-year-old man who presented with dysphagia.Upper
      gastrointestinal endoscopy revealed a protruding lesion in the lower thoracic
      esophagus.Pathological analysis of the lesion showed squamous cell
      carcinoma.Laboratory data showed leukocytosis(21,200/mL)despite no evidence of
      infection, and the serum levels of granulocyte colony-stimu- lating factor(G
      CSF)were elevated to 283 pg/mL.We diagnosed him with esophageal squamous cell
      carcinoma(Lt, type 1, cT4N4M0, cStage IV a).After administering 2 courses of
      docetaxel plus cisplatin plus S-1(DCS)as neoadjuvant chemotherapy, the patient
      underwent surgery.The pathological diagnosis was pType 2, T2, N4, M0, pStage IV
      a. G-CSF immunostaining was positive in tumor cells.After the surgery, the number
      of leukocytes and serum G-CSF levels decreased to within normal limits.Adjuvant
      chemotherapy was administered.

PMID- 30237382
TI  - [A Case of Advanced Gastric Cancer with Bladder Metastasis].
AB  - A 61-year-old man was referred to the urology department in our hospital with
      gross hematuria and hydro nephrosis. Cystoscopy revealed a smooth mass lesion in
      his bladder, and a transurethral biopsy was performed. Signet ring cell carcinoma
      was found in the submucosa. Upper gastrointestinal endoscopy revealed an
      ulcerated lesion in his gastric body. Biopsy specimens obtained from the
      ulcerated lesion showed signet ring cell carcinoma. No other primary lesions were
      detected using colonoscopy, gallium scintigraphy, or computed tomography of the
      chest. He was ultimately diagnosed with advanced gastric cancer with bladder
      metastasis. He was prescribed combination chemotherapy of cisplatin and tegafur,
      gimeracil, oteracil potassium, and trastuzumab. After 2 courses of chemotherapy,
      there was a decrease in the size of both the gastric and bladder lesions. There
      was also a significant decrease in the tumor marker levels. He is currently alive
      after 7 courses of chemotherapy.

PMID- 30237381
TI  - [Definitive Radiotherapy for Esophageal Squamous Cell Carcinoma after Allogeneic
      Hematopoietic Stem Cell Transplantation with Conditioning of Total Body
      Irradiation].
AB  - A 24-year-old man with acute lymphoblasticleukemia underwent allogeneicperipheral
      blood stem cell transplantation (allo-PBSCT)from a human leukocyte antigen
      matched sibling after myeloablative conditioning, with a regimen including total
      body irradiation(TBI)(12 Gy/6 fractions), 6 years ago. The patient developed
      extensive chronic graft-versus-host disease(cGVHD)of the skin, mouth, liver, and
      gut four months after allo-PBSCT. Treatment with cyclosporine and prednisolone
      was necessary to control the cGVHD. Six years after allo-PBSCT, the patient
      experienced odynophagia and was diagnosed with cervical esophageal squamous cell
      carcinoma(cT1bN1M0, cStage II B). Because we considered laryngeal preservation,
      risk of anastomotic leakage, and infection related to the operation, the patient
      was planned to receive chemoradio- therapy with 5-fluorouracil and cisplatin.
      Regarding irradiation, the patient received radiotherapy(50.4 Gy/28 fractions)for
      a primary tumor and lymph node without an elective nodal area. The patient
      achieved complete response and remained disease- free without any treatment
      related complications for 3 years.

PMID- 30237383
TI  - [A Case of Interstitial Pneumonitis Induced by TAS-102 for Liver and Lung
      Metastasis of Colorectal Cancer].
AB  - A 78-year-old man who developed metastatic liver and lung cancer after undergoing
      surgery for rectal and sigmoid colon cancer was treated with TAS-102 as fourth
      line chemotherapy. He developed high fever and dyspnea and was referred to the
      emergency room 16 days after receiving the first course of TAS-102. Chest X-ray
      and computed tomography examinations showed bacterial pneumonia. He was treated
      with tazobactam/piperacillin, but developed severe dyspnea 4 days later. A
      diffuse ground-glass appearance was observed in both the lungs on chest X-ray
      examination, and drug-induced interstitial pneumonitis was suspected. Oxygenation
      and respiratory support were immediately administered, and steroid pulse therapy
      with methylprednisolone at 1,000mg/day was initiated. His symptoms and
      radiographic findings dramatically improved. The TAS102-J003 trial, a double
      blind phase 2 trial, showed that interstitial pneumonitis occurs at a rate of
      only 0.9%, but can lead to severe complications, as observed in the present case.
      The possibility of interstitial pneumonitis should always be considered when a
      patient develops a fever and respiratory disorder during treatment containing TAS
      102.

PMID- 30237384
TI  - [A Case of Hypophosphatemia Induced by Administration of Amrubicin in a Patient
      with Small Cell Lung Cancer].
AB  - A man in his 50s with small cell lung cancer received amrubicin as the fourth
      line therapy from August 201X-1. Serum phosphorus levels before treatment were
      normal at 2.9mg/dL, but grade 2 hypophosphatemia(2.1mg/dL)was observed at the
      beginning of the 2nd course. He underwent laryngoplasty after the 4th course.
      Retreatment was initiated in June 201X due to disease progression. After
      reinitiating treatment, the disease developed to grade 3 hypophosphatemia. As we
      identi- fied lower levels(1.1mg/dL)at the start of the 10th course, a pharmacist
      proposed oral phosphate therapy to the attending physician, which we
      administered. After then, the levels improved to 2.2mg/dL; thus, oral phosphate
      therapy was interrupted. However, because of a decline in serum phosphorus levels
      to grade 3, we administered the therapy again, and observed favorable
      improvement. For hypophosphatemia in this case, general reasons in clinical
      practice were not applicable; thus, amrubicin is considered to be a most possible
      cause.

PMID- 30237385
TI  - [A Case of Intussusception in the Jejunum Due to Small Intestinal
      Adenocarcinoma].
AB  - The patient was a woman in her 60's with an 11-month history ofpersistent
      epigastralgia and abdominal distension, without abnormal findings on upper
      endoscopy, abdominal ultrasonography, and abdominal computed tomography in other
      hospitals. She presented to our hospital with a complaint off requent vomiting;
      abdominal CT indicated intussusception in the jejunum due to a small intestinal
      tumor, and laparoscopic exploration and partial jejunectomy were performed. The
      histopathological diagnosis was tub1>tub2>pap, pT4(SE), pN1, pPM0, pDM0, pStage
      III A. She was treated with oral chemotherapy( S-1)and developed no recurrence 7
      months after surgery. Laparoscopic exploration was useful to detect
      intussusception in the jejunum due to small intestinal adenocarcinoma.

PMID- 30237386
TI  - [Primary Small Bowel Tumor with Simultaneous Lung Metastases from Rectal Cancer -
      A Case Report].
AB  - A 56-year-old woman was diagnosed with rectal cancer and liver metastases(Stage
      IV), and underwent low anterior resection and laparoscopic partial hepatectomy.
      The patient received adjuvant chemotherapy(mFOLFOX6 for 24 weeks), but developed
      multiple lung metastases 11 months later. Before undergoing a pulmonary
      resection, the patient presented with acute small bowel obstruction. Abdominal
      computed tomography showed small bowel stenosis due to a tumor, and we suspected
      peritoneal metastases from the rectal tumor. We performed partial resection of
      the small intestine, and histopathological examination revealed a primary small
      bowel tumor. The patient was discharged to her home without complications, and
      later underwent pulmonary resections for bilateral lung metastases. We usually
      suspect that small bowel obstruction is due to peritoneal metastases in patients
      with advanced colorectal tumors, but must consider the rare possibility of a
      separate primary small bowel tumor, especially in patients with a solitary
      lesion. We report a rare primary small bowel tumor after FOLFOX treatment in a
      patient with Stage IV rectal cancer.

PMID- 30237387
TI  - [A Case of Bone Marrow Carcinomatosis of Occult Breast Cancer Treated Effectively
      with Fulvestrant].
AB  - A 63-year-old woman experienced left cervical lymph node swelling since May 2012.
      Based on PET-CT findings, metastases of a malignant tumor to the mediastinal,
      axillary, and left cervical lymph nodes were suspected. Her left cervical lymph
      node biopsy revealed metastatic carcinoma of occult cancer, because no primary
      tumor could be identified despite the specific examinations. She rejected further
      therapeutic intervention. In July 2013, she was admitted because of anemia,
      cardiac failure, and fever. She was diagnosed with bone marrow carcinomatosis
      from occult cancer based on her bone marrow biopsy. Metastatic breast cancer was
      mostly considered because she tested positive for estrogen and progesterone
      receptors, CA15-3 levels were increased, and her axillary lymph nodes were
      swollen. Fulvestrant and zoledronic acid were administered and continued for 20
      months, with improvement in anemia and tumor marker levels, and also maintenance
      of partial response.

PMID- 30237388
TI  - [Regimen Management and Implementation Procedure for Outpatient Chemotherapy in
      Regional General Hospital].

PMID- 30237389
TI  - Clinical Features and Surveillance of Very Late Hepatocellular Carcinoma
      Recurrence After Liver Transplantation.
AB  - BACKGROUND This study aimed to assess patterns of hepatocellular carcinoma (HCC)
      recurrence after liver transplantation (LT) and to establish long-term
      surveillance protocols for late HCC recurrence. MATERIAL AND METHODS The 232 LT
      recipients experiencing subsequent HCC recurrence were categorized as Group 1,
      early recurrence (within 1 year of LT; n=117); Group 2, late recurrence
      (occurring in years 2-5; n=93); and Group 3, very late recurrence (after year 5;
      n=22). RESULTS Recurrence was detected by only elevated tumor marker levels in
      11.1%, 30.1%, and 45.5% of patients in Groups 1, 2, and 3, respectively
      (p<0.001). The proportion of intrahepatic and extrahepatic metastases was similar
      in all 3 groups. Common sites of extrahepatic metastasis were the lung and bone;
      these were also similar across the 3 groups. Overall post-recurrence patient
      survival rates were 60.2% at 1 year, 28.2% at 3 years, 20.5% at 5 years, and 7.0%
      at 10 years. Median post-recurrence survival periods were 10.2, 23.8, and 37.0
      months in Groups 1, 2, and 3, respectively. CONCLUSIONS While the pattern of HCC
      recurrence was similar regardless of time of recurrence, post-recurrence survival
      was significantly longer in patients with later recurrence. Long-term
      surveillance for HCC recurrence beyond 5 years after LT is recommended.

PMID- 30237390
TI  - Insulinoma: A Rare Cause of Hypoglycemia in Childhood.
AB  - BACKGROUND Insulinomas are pancreatic neuroendocrine tumors that cause non
      ketotic hypoglycemia due to hyperinsulinism; they are extremely rare, especially
      in children. CASE REPORT We present a case of a sporadic insulinoma in an 11-year
      old boy who had episodes of self-limited drowsiness and behavior changes over a 3
      month period, thought to be caused by psychological issues. Non-ketotic
      hypoglycemia was confirmed at our center. A fasting blood test found
      inappropriately elevated insulin levels during hypoglycemia, undetectable beta
      hydroxybutyrate, and increased C-peptide levels in line with insulin levels. Anti
      insulin antibodies were negative and antidiabetic drugs untraceable. The glucagon
      stimulation test was positive. Growth hormone, adrenocorticotropin hormone, and
      phosphorus and calcium metabolism were normal. Dual-phase computed tomography
      detected a lesion compatible with an insulinoma. Endoscopic ultrasound showed a
      homogenous lesion at the junction of the body and tail of the pancreas.
      Histologic analysis of a fine-needle aspiration biopsy was compatible with
      neuroendocrine neoplasia. Preoperatively, a fractional diet avoiding fast
      absorbing carbohydrates maintained normal glucose blood levels. Enucleation was
      not possible, so the lesion was resected along with portions of the body and tail
      of the pancreas. The well-differentiated tumor measured 15 mm x 13 mm.
      Postoperative blood glucose levels were correct, allowing a normal diet.
      CONCLUSIONS In children with unspecific symptoms compatible with hypoglycemia,
      blood glucose must be evaluated to confirm low blood glucose levels. Determining
      blood ketone levels is important for the differential diagnosis. The diagnostic
      approach to pediatric insulinoma represents a challenge for multidisciplinary
      teamwork.

PMID- 30237391
TI  - Sinomenine Regulates Inflammatory Response and Oxidative Stress via Nuclear
      Factor kappa B (NF-kappaB) and NF-E2-Related Factor 2 (Nrf2) Signaling Pathways
      in Ankle Fractures in Children.
AB  - BACKGROUND This study aimed to investigate the effects of SIN on ankle fracture
      and the underlying mechanisms in MG-63 cells. MATERIAL AND METHODS qRT-PCR and
      ELISA assay were used to detect the mRNA and protein levels of cytokines in
      peripheral blood of children with or without ankle fracture. The expression and
      activity of antioxidant and detoxifying enzymes were detected by ELISA assay.
      Pretreated MG-63 cells with/without SIN were stimulated with 1 MUg/ml bradykinin
      (BK). A CCK-8 kit was used to detect the cell viability. The cytokines produced
      from MG-63 cells were detected by Western blotting and qRT-PCR. Moreover, Western
      blotting was used to detect the levels of p-p38 and p-NF-kappaB (p65), and the
      activation level of the Nrf2 signaling pathway was examined by qRT-PCR and
      Western blotting. RESULTS In this study, we found that compared with the healthy
      children, the mRNA and protein levels of interleukin (IL)-1beta, IL-6, and tumor
      necrosis factor-alpha (TNF-alpha) were significantly upregulated in children with
      ankle fracture. In addition, the expression and activity of antioxidant and
      detoxifying enzymes were imbalanced in children with ankle fracture. SIN
      treatment did not have a cytotoxic effect on MG-63 cells. SIN dose-dependently
      suppressed BK-induced upregulation of IL-1beta, IL-6, TNF-alpha, p-p38, and p-NF
      kappaB (p65). Furthermore, SIN dramatically inhibited oxidative stress induced by
      BK via balancing the expression and activity of antioxidant and detoxifying
      enzymes and inhibited the activation of Nrf2 signaling. CONCLUSIONS SIN might be
      a potential agent for the treatment of ankle fracture through reducing
      inflammatory response and oxidative stress.

PMID- 30237393
TI  - BRAF inhibition causes resilience of melanoma cell lines by inducing the
      secretion of FGF1.
AB  - Approximately half of all melanoma patients harbour activating mutations in the
      serine/threonine kinase BRAF. This is the basis for one of the main treatment
      strategies for this tumor type, the targeted therapy with BRAF and MEK
      inhibitors. While the initial responsiveness to these drugs is high, resistance
      develops after several months, frequently at sites of the previously responding
      tumor. This indicates that tumor response is incomplete and that a certain tumor
      fraction survives even in drug-sensitive patients, e.g., in a therapy-induced
      senescence-like state. Here, we show in several melanoma cell lines that BRAF
      inhibition induces a secretome with stimulating effect on fibroblasts and naive
      melanoma cells. Several senescence-associated factors were found to be
      transcribed and secreted in response to BRAF or MEK inhibition, among them
      members of the fibroblast growth factor family. We identified the growth factor
      FGF1 as mediator of resilience towards BRAF inhibition, which limits the pro
      apoptotic effects of the drug and activates fibroblasts to secrete HGF. FGF1
      regulation was mediated by the PI3K pathway and by FRA1, a direct target gene of
      the MAPK pathway. When FGFR inhibitors were applied in parallel to BRAF
      inhibitors, resilience was broken, thus providing a rationale for combined
      therapeutical application.

PMID- 30237392
TI  - Helicobacter pylori infection and inflammatory bowel disease: a crosstalk between
      upper and lower digestive tract.
AB  - Helicobacter pylori has coexisted with humans for approximately 60,000 years and
      greater than 50% of the global population is infected with H. pylori. H. pylori
      was successfully cultured in vitro in 1983 and studies of H. pylori have achieved
      substantial advances over the last 35 years. Since then, H. pylori has been
      characterized as the primary pathogenic factor for chronic gastritis, peptic
      ulcer, and gastric malignancy. Numerous patients have received H. pylori
      eradication treatment, but only 1-2% of H. pylori-infected individuals ultimately
      develop gastric cancer. Recently, numerous epidemiological and basic experimental
      studies suggested a role for chronic H. pylori infection in protecting against
      inflammatory bowel disease (IBD) by inducing systematic immune tolerance and
      suppressing inflammatory responses. Here we summarize the current research
      progress on the association between H. pylori and IBD, and further describe the
      detailed molecular mechanism underlying H. pylori-induced dendritic cells (DCs)
      with the tolerogenic phenotype and immunosuppressive regulatory T cells (Tregs).
      Based on the potential protective role of H. pylori infection on IBD, we suggest
      that the interaction between H. pylori and the host is complicated, and H. pylori
      eradication treatment should be administered with caution, especially for
      children and young adults.

PMID- 30237394
TI  - MTP18 overexpression contributes to tumor growth and metastasis and associates
      with poor survival in hepatocellular carcinoma.
AB  - BACKGROUND: Human MTP18 (mitochondrial protein 18 kDa) is a novel nuclear-encoded
      mitochondrial membrane protein that is involved in controlling mitochondrial
      fission. Our bioinformatic analysis of TCGA data revealed an aberrant
      overexpression of MTP18 in hepatocellular carcinoma (HCC). We analyzed its
      biological effects and prognostic significance in this malignancy. METHODS: MTP18
      expression was evaluated by qRT-PCR and western blot analysis in 20 paired tumor
      and peritumor tissues. Clinical impact of MTP18 overexpression was assessed in
      156 patients with HCC. The effects of MTP18 knockdown or overexpression on cell
      growth and metastasis were determined by cell proliferation, colony formation,
      cell cycle, apoptosis, migration, and invasion assays. Furthermore, the
      underlying molecular mechanisms by which MTP18 overexpression promoted HCC cell
      growth and metastasis were explored. RESULTS: MTP18 was commonly overexpressed in
      HCC tissues mainly due to the downregulation of miR-125b, which significantly
      contributed to poor prognosis of HCC patients. Functional experiments revealed
      that MTP18 promoted both the growth and metastasis of HCC cells by inducing the
      progression of cell cycle, epithelial to mesenchymal transition (EMT) and
      production of MMP-9, and suppressing cell apoptosis. Mechanistically, increased
      mitochondrial fission and subsequent ROS production was found to be involved in
      the promotion of growth and metastasis by MTP18 in HCC cells. CONCLUSIONS: MTP18
      plays a pivotal oncogenic role in hepatocellular carcinogenesis; its
      overexpression may serve as a novel prognostic factor and a therapeutic target in
      HCC.

PMID- 30237395
TI  - Distinct multilevel misregulations of Parkin and PINK1 revealed in cell and
      animal models of TDP-43 proteinopathy.
AB  - Parkin and PINK1 play an important role in mitochondrial quality control, whose
      malfunction may also be involved in the pathogenesis of amyotrophic lateral
      sclerosis (ALS). Excessive TDP-43 accumulation is a pathological hallmark of ALS
      and is associated with Parkin protein reduction in spinal cord neurons from
      sporadic ALS patients. In this study, we reveal that Parkin and PINK1 are
      differentially misregulated in TDP-43 proteinopathy at RNA and protein levels.
      Using knock-in flies, mouse primary neurons, and TDP-43Q331K transgenic mice, we
      further unveil that TDP-43 downregulates Parkin mRNA, which involves an
      unidentified, intron-independent mechanism and requires the RNA-binding and the
      protein-protein interaction functions of TDP-43. Unlike Parkin, TDP-43 does not
      regulate PINK1 at an RNA level. Instead, excess of TDP-43 causes cytosolic
      accumulation of cleaved PINK1 due to impaired proteasomal activity, leading to
      compromised mitochondrial functions. Consistent with the alterations at the
      molecular and cellular levels, we show that transgenic upregulation of Parkin but
      downregulation of PINK1 suppresses TDP-43-induced degenerative phenotypes in a
      Drosophila model of ALS. Together, these findings highlight the challenge
      associated with the heterogeneity and complexity of ALS pathogenesis, while
      pointing to Parkin-PINK1 as a common pathway that may be differentially
      misregulated in TDP-43 proteinopathy.

PMID- 30237396
TI  - Author Correction: MYC-driven epigenetic reprogramming favors the onset of
      tumorigenesis by inducing a stem cell-like state.
AB  - The original version of this Article contained an error in the spelling of the
      author Miriam Gaggianesi, which was incorrectly given as Miriam Giaggianesi.
      Furthermore, the affiliation details for Gabriella Gaudioso, Valentina Vaira, and
      Silvano Bosari incorrectly omitted 'Division of Pathology, Fondazione IRCCS Ca'
      Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy'. Finally, the
      affiliation details for Alice Turdo, Miriam Gaggianesi, Aurora Chinnici and Elisa
      Lipari were incorrectly given as 'Dipartimento di Biotecnologie Mediche e
      Medicina Legale Sezione di Biochimica Medica, Facolta di Medicina e Chirurgia,
      Policlinico "P.Giaccone", Universita di Palermo, Palermo, 90127, Italy'. The
      correct affiliation is 'Department of Surgical, Oncological and Stomatological
      Sciences, University of Palermo, Palermo, 90127, Italy'. These errors have now
      been corrected in both the PDF and HTML versions of the Article.

PMID- 30237397
TI  - Melittin-induced long non-coding RNA NONHSAT105177 inhibits proliferation and
      migration of pancreatic ductal adenocarcinoma.
AB  - Long non-coding RNAs (lncRNAs) play crucial roles in the pathogenesis of
      pancreatic ductal adenocarcinoma (PDAC). Previously, we found that melittin
      treatment suppressed PDAC tumor growth. However, it is unclear whether lncRNAs
      have any role in the melittin-induced suppression of PDAC. In this study, we used
      microarray data to identify 844 lncRNAs that were significantly differentially
      expressed in response to melittin treatment. Of these lncRNAs, we focused on the
      lncRNA NONHSAT105177, which had about a 22-fold increase in expression with
      melittin treatment. We found that melittin treatment increased NONHSAT105177
      expression in PDAC cell lines but not in normal pancreatic ductal epithelial cell
      line. NONHSAT105177 expression was significantly lower in PDAC cancer tissues
      than in adjacent noncancerous tissues. Additionally, overexpression of
      NONHSAT105177 inhibited PDAC cell proliferation, migration, and the epithelial
      mesenchymal transition (EMT), both in vitro and in vivo. Consistent with the
      mechanism of action of melittin, NONHSAT105177 significantly downregulated
      cholesterol pathway genes, including Clusterin (CLU). Moreover, we found that
      NONHSAT105177 trafficking was mediated by exosomes. The combined findings of our
      current and previous studies suggest that NONHSAT105177 mediated the melittin
      induced inhibition of PDAC cell growth and metastasis, which indicated a
      potential target for developing new strategies.

PMID- 30237399
TI  - Identification of active sites on supported metal catalysts with carbon nanotube
      hydrogen highways.
AB  - Catalysts consisting of metal particles supported on reducible oxides exhibit
      promising activity and selectivity for a variety of current and emerging
      industrial processes. Enhanced catalytic activity can arise from direct contact
      between the support and the metal or from metal-induced promoter effects on the
      oxide. Discovering the source of enhanced catalytic activity and selectivity is
      challenging, with conflicting arguments often presented based on indirect
      evidence. Here, we separate the metal from the support by a controlled distance
      while maintaining the ability to promote defects via the use of carbon nanotube
      hydrogen highways. As illustrative cases, we use this approach to show that the
      selective transformation of furfural to methylfuran over Pd/TiO2 occurs at the Pd
      TiO2 interface while anisole conversion to phenol and cresol over Cu/TiO2 is
      facilitated by exposed Ti3+ cations on the support. This approach can be used to
      clarify many conflicting arguments in the literature.

PMID- 30237400
TI  - HS-1371, a novel kinase inhibitor of RIP3-mediated necroptosis.
AB  - Necroptosis is a type of programmed cell death that usually occurs under
      apoptosis-deficient conditions. Receptor-interacting protein kinase-3 (RIP3, or
      RIPK3) is a central player in necroptosis, and its kinase activity is essential
      for downstream necroptotic signaling events. Since RIP3 kinase activity has been
      associated with various diseases, the development of specific RIP3 inhibitors is
      an attractive strategy for therapeutic application. In this study, we identified
      a potent RIP3 inhibitor, HS-1371, by the extensive screening of chemical
      libraries focused on kinases. HS-1371 directly binds to RIP3 in an ATP
      competitive and time-independent manner, providing a mechanism of action.
      Moreover, the compound inhibited TNF-induced necroptosis but did not inhibit TNF
      induced apoptosis, indicating that this novel inhibitor has a specific inhibitory
      effect on RIP3-mediated necroptosis via the suppression of RIP3 kinase activity.
      Our results suggest that HS-1371 could serve as a potential preventive or
      therapeutic agent for diseases involving RIP3 hyperactivation.

PMID- 30237398
TI  - Vascularization converts the lineage fate of bone mesenchymal stem cells to
      endothelial cells in tissue-engineered bone grafts by modulating FGF2-RhoA/ROCK
      signaling.
AB  - The prevascularization of tissue-engineered bone grafts (TEBGs) has been shown to
      accelerate capillary vessel ingrowth in bone defect remodeling and to enhance new
      bone formation. However, the exact mechanisms behind this positive effect remain
      unknown. Here, we report that basic fibroblast growth factor (FGF2)-Ras homolog
      gene family member A (RhoA)/Rho-associated protein kinase (ROCK) signaling
      functions as a molecular switch to regulate the lineage fate of bone mesenchymal
      stem cells (BMSCs) and that prevascularization promotes the cell fate switch,
      which contributes to increased bone regeneration with the use of prevascularized
      TEBGs compared with control TEBGs. Prevascularized TEBGs enhanced the in vivo
      endothelial differentiation of BMSCs by inhibiting RhoA/ROCK signaling. In vitro
      data more clearly showed that BMSCs differentiated into von Willebrand factor
      (vWF)-positive endothelial cells, and FGF2-induced inhibition of RhoA/ROCK
      signaling played a key role. Our novel findings uncovered a new mechanism that
      stimulates the increased vascularization of engineered bone and enhanced
      regeneration by promoting the endothelial differentiation of BMSCs implanted in
      TEBGs. These results offer a new molecular target to regulate TEBG-induced bone
      regeneration.

PMID- 30237401
TI  - Resveratrol improves human umbilical cord-derived mesenchymal stem cells repair
      for cisplatin-induced acute kidney injury.
AB  - Human umbilical cord-derived mesenchymal stem cells (hucMSCs) are a promising
      tool for damaged tissues repair, especially for the kidney. However, their
      efficacy requires improvement. In order to optimize the clinical utility of
      hucMSCs, we adopted a strategy of treating hucMSCs with 20 MUmol/L of resveratrol
      (Res-hucMSCs), applying it in a cisplatin-induced acute kidney injury model.
      Interestingly, we found that Res-hucMSCs exhibited a more efficient repairing
      effect than did hucMSCs. Resveratrol-promoted hucMSCs secreted platelet-derived
      growth factor-DD (PDGF-DD) into renal tubular cells resulting in downstream
      phosphorylation of extracellular signal-regulated kinase (ERK), which inhibited
      renal tubular cells apoptosis. In contrast, PDGF-DD knockdown impaired the renal
      protection of Res-hucMSCs. In addition, angiogenesis induced by PDGF-DD in
      endothelial cells was also involved in the renal protection of Res-hucMSCs. The
      conditioned medium of Res-hucMSCs accelerated proliferation and migration of
      vascular endothelial cells in vitro and CD31 was in a high-level expression in
      Res-hucMSCs group in vivo. Nevertheless, the angiogenesis was abrogated when Res
      hucMSCs were treated with PDGF-DD siRNA. In conclusion, our findings showed that
      resveratrol-modified hucMSCs activated ERK pathway in renal tubular cells and
      promoted angiogenesis in endothelial cells via paracrine PDGF-DD, which could be
      a novel strategy for enhancing the therapy efficacy of hucMSCs in cisplatin
      induced kidney injury.

PMID- 30237402
TI  - Female mice lacking Ftx lncRNA exhibit impaired X-chromosome inactivation and a
      microphthalmia-like phenotype.
AB  - X-chromosome inactivation (XCI) is an essential epigenetic process in female
      mammalian development. Although cell-based studies suggest the potential
      importance of the Ftx long non-protein-coding RNA (lncRNA) in XCI, its
      physiological roles in vivo remain unclear. Here we show that targeted deletion
      of X-linked mouse Ftx lncRNA causes eye abnormalities resembling human
      microphthalmia in a subset of females but rarely in males. This inheritance
      pattern cannot be explained by X-linked dominant or recessive inheritance, where
      males typically show a more severe phenotype than females. In Ftx-deficient mice,
      some X-linked genes remain active on the inactive X, suggesting that defects in
      random XCI in somatic cells cause a substantially female-specific phenotype. The
      expression level of Xist, a master regulator of XCI, is diminished in females
      homozygous or heterozygous for Ftx deficiency. We propose that loss-of-Ftx lncRNA
      abolishes gene silencing on the inactive X chromosome, leading to a female
      microphthalmia-like phenotype.

PMID- 30237404
TI  - Brain Fogginess and SIBO: A Link or Just a Mirage?

PMID- 30237403
TI  - CCN6-mediated MMP-9 activation enhances metastatic potential of human
      chondrosarcoma.
AB  - Chondrosarcomas are primary malignant bone tumors that have a poor prognosis.
      WNT1-inducible signaling pathway protein-3 (WISP-3, also termed CCN6) belongs to
      the CCN family of proteins and is implicated in the regulation of various
      cellular functions, such as cell proliferation, differentiation, and migration.
      It is unknown as to whether CCN6 affects human chondrosarcoma metastasis. We show
      how CCN6 promotes chondrosarcoma cell migration and invasion via matrix
      metallopeptidase-9 (MMP)-9 expression. These effects were abolished by
      pretreatment of chondrosarcoma cells with PI3K, Akt, mTOR, and NF-kappaB
      inhibitors or short interfering (si)RNAs. Our investigations indicate that CCN6
      facilitates metastasis through the PI3K/Akt/mTOR/NF-kappaB signaling pathway.
      CCN6 and MMP-9 expression was markedly increased in the highly migratory
      JJ012(S10) cell line compared with the primordial cell line (JJ012) in both in
      vitro and in vivo experiments. CCN6 knockdown suppressed MMP-9 production in
      JJ012(S10) cells and attenuated cell migration and invasion ability. Importantly,
      CCN6 knockdown profoundly inhibited chondrosarcoma cell metastasis to lung. Our
      findings reveal an important mechanism underlying CCN6-induced metastasis and
      they highlight the clinical significance between CCN6 and MMP-9 in regard to
      human chondrosarcoma. CCN6 appears to be a promising therapeutic target in
      chondrosarcoma metastasis.

PMID- 30237405
TI  - CRISPR-typing PCR (ctPCR), a new Cas9-based DNA detection method.
AB  - This study develops a new method for detecting and typing target DNA based on
      Cas9 nuclease, which was named as ctPCR, representing Cas9-sgRNA- or CRISPR
      typing PCR. The technique can detect and type target DNA easily, rapidly,
      specifically, and sensitively. This technique detects target DNA in three steps:
      (1) amplifying target DNA with PCR by using a pair of universal primers (PCR1);
      (2) treating PCR1 products with a process referred to as CAT, representing Cas9
      cutting, A tailing and T adaptor ligation; (3) amplifying the CAT-treated DNA
      with PCR by using a pair of general-specific primers (gs-primers) (PCR2). This
      method was verified by detecting HPV16 and HPV18 L1 gene in 13 different high
      risk human papillomavirus (HPV) subtypes. This method was also verified by
      detecting the L1 and E6-E7 genes of two high-risk HPVs (HPV16 and 18) in cervical
      carcinoma cells and many clinical samples. In this method, PCR1 was performed to
      determine if the detected DNA sample contained the target DNA (such as virus
      infection), while PCR2 was performed to discriminate which genotypic target DNA
      was present in the detected DNA sample (such as virus subtypes). Based on these
      proof-of-concept experiments, this study provides a new CRISPR/Cas9-based DNA
      detection and typing method.

PMID- 30237406
TI  - Strongly lensed repeating fast radio bursts as precision probes of the universe.
AB  - Fast radio bursts (FRBs), bright transients with millisecond durations at ~GHz
      and typical redshifts probably >0.8, are likely to be gravitationally lensed by
      intervening galaxies. Since the time delay between images of strongly lensed FRB
      can be measured to extremely high precision because of the large ratio ~109
      between the typical galaxy-lensing delay time [Formula: see text] (10 days) and
      the width of bursts [Formula: see text] (ms), we propose strongly lensed FRBs as
      precision probes of the universe. We show that, within the flat LambdaCDM model,
      the Hubble constant H0 can be constrained with a ~0.91% uncertainty from 10 such
      systems probably observed with the square kilometer array (SKA) in <30 years.
      More importantly, the cosmic curvature can be model independently constrained to
      a precision of ~0.076. This constraint can directly test the validity of the
      cosmological principle and break the intractable degeneracy between the cosmic
      curvature and dark energy.

PMID- 30237407
TI  - Thermal management of epidermal electronic devices/skin system considering
      insensible sweating.
AB  - Thermal management of the system consisting of epidermal electronics devices
      (EEDs) and skin is critically important since a few degrees in temperature
      increase may induce thermal discomfort. In this paper, considering insensible
      sweating, a three-dimensional analytical thermal model, validated by finite
      element analysis, is developed to derive analytical expressions for the steady
      temperature distributions in the EED/skin system. The influences of various
      parameters including the thickness and thermal conductivity of the substrate in
      EEDs on the maximum skin temperature are investigated. The comfort analysis is
      then carried out based on the model to provide design guidelines for optimizing
      the geometric and material properties of EEDs to avoid the adverse thermal
      effects. These results pave the theoretical foundation for thermal management of
      EEDs/skin system in practical applications.

PMID- 30237408
TI  - miR-665 promotes hepatocellular carcinoma cell migration, invasion, and
      proliferation by decreasing Hippo signaling through targeting PTPRB.
AB  - Growing evidence suggests that aberrant microRNA (miRNA) expression contributes
      to hepatocellular carcinoma (HCC) development and progression. However, the
      potential role and mechanism of miR-665 in the progression of liver cancer
      remains largely unknown. Our current study showed that miR-665 expression was
      upregulated in HCC cells and tissues. High expression of miR-665 exhibited more
      severe tumor size, vascular invasion and Edmondson grading in HCC patients. Gain-
      or loss-of-function assays demonstrated that miR-665 promoted cell proliferation,
      migration, invasion, and the epithelial-mesenchymal transition (EMT) of HCC cells
      in vitro and in vivo. Tyrosine phosphatase receptor type B (PTPRB) was
      downregulated in HCC tissues, and was negatively correlated with miR-665
      expression. Through western blotting and luciferase reporter assay, PTPRB was
      identified as a direct downstream target of miR-665. Restoration of PTPRB
      reverses the effects of miR-665 on HCC migration, invasion, and cell
      proliferation. A mechanistic study showed that PTPTRB mediated the functional
      role of miR-665 through regulation of the Hippo signaling pathway. In conclusion,
      our results suggested that miR-665 was a negative regulator of the PTPRB and
      could promote tumor proliferation and metastasis in HCC through decreasing Hippo
      signaling pathway activity, which can be a potential target for HCC treatment.

PMID- 30237409
TI  - Intermittent hypoxia regulates vasoactive molecules and alters insulin-signaling
      in vascular endothelial cells.
AB  - Vascular dysfunction and insulin resistance (IR) are associated with obstructive
      sleep apnea (OSA), which is characterized by frequent episodes of nocturnal
      intermittent hypoxia (IH). While it is recognized that the balance between
      vasoconstrictive (endothelin-1) and vasodilatory molecules (nitric oxide, NO)
      determine vascular profile, molecular mechanisms contributing to vascular
      dysfunction and IR in OSA are not completely understood. Caveolin-1 is a membrane
      protein which regulates endothelial nitric oxide synthase (eNOS) activity which
      is responsible for NO generation and cellular insulin-signaling. Hence, we
      examined the effects of IH on caveolin-1, eNOS, and endothelin-1 in human
      coronary artery endothelial cells in the context of IR. Chronic 3-day IH exposure
      up-regulated caveolin-1 and endothelin-1 expression while reducing NO. Also, IH
      altered insulin-mediated activation of AKT but not ERK resulting in increased
      endothelin-1 transcription. Similarly, caveolin-1 overexpression attenuated basal
      and insulin-stimulated NO synthesis along with impaired insulin-dependent
      activation of AKT and eNOS, with no effect on insulin-stimulated ERK1/2
      phosphorylation and endothelin-1 transcription. Our data suggest that IH
      contributes to a vasoconstrictive profile and to pathway-selective vascular IR,
      whereby insulin potentiates ET-1 expression. Moreover, IH may partly mediate its
      effects on NO and insulin-signaling via upregulating caveolin-1 expression.

PMID- 30237410
TI  - White matter aberrations and age-related trajectories in patients with
      schizophrenia and bipolar disorder revealed by diffusion tensor imaging.
AB  - Supported by histological and genetic evidence implicating myelin,
      neuroinflammation and oligodendrocyte dysfunction in schizophrenia spectrum
      disorders (SZ), diffusion tensor imaging (DTI) studies have consistently shown
      white matter (WM) abnormalities when compared to healthy controls (HC). The
      diagnostic specificity remains unclear, with bipolar disorders (BD) frequently
      conceptualized as a less severe clinical manifestation along a psychotic
      spectrum. Further, the age-related dynamics and possible sex differences of WM
      abnormalities in SZ and BD are currently understudied. Using tract-based spatial
      statistics (TBSS) we compared DTI-based microstructural indices between SZ (n =
      128), BD (n = 61), and HC (n = 293). We tested for age-by-group and sex-by-group
      interactions, computed effect sizes within different age-bins and within genders.
      TBSS revealed global reductions in fractional anisotropy (FA) and increases in
      radial (RD) diffusivity in SZ compared to HC, with strongest effects in the body
      and splenium of the corpus callosum, and lower FA in SZ compared to BD in right
      inferior longitudinal fasciculus and right inferior fronto-occipital fasciculus,
      and no significant differences between BD and HC. The results were not strongly
      dependent on age or sex. Despite lack of significant group-by-age interactions, a
      sliding-window approach supported widespread WM involvement in SZ with most
      profound differences in FA from the late 20 s.

PMID- 30237411
TI  - Reproducibility study on myocardial strain assessment using fast-SENC cardiac
      magnetic resonance imaging.
AB  - Myocardial strain is a well validated parameter for estimating left ventricular
      (LV) performance. The aim of our study was to evaluate the inter-study as well as
      intra- and interobserver reproducibility of fast-SENC derived myocardial strain.
      Eighteen subjects (11 healthy individuals and 7 patients with heart failure)
      underwent a cardiac MRI examination including fast-SENC acquisition for
      evaluating left ventricular global longitudinal (GLS) and circumferential strain
      (GCS) as well as left ventricular ejection fraction (LVEF). The examination was
      repeated after 63 [range 49-87] days and analyzed by two experienced observers.
      Ten datasets were repeatedly assessed after 1 month by the same observer to test
      intraobserver variability. The reproducibility was measured using the intraclass
      correlation coefficient (ICC) and Bland-Altman analysis. Patients with heart
      failure demonstrated reduced GLS and GCS compared to healthy controls (-15.7 +/-
      3.7 vs. -20.1 +/- 1.4; p = 0.002 for GLS and -15.3 +/- 3.7 vs. -21.4 +/- 1.1; p =
      0.001 for GCS). The test-retest analysis showed excellent ICC for LVEF (0.92),
      GLS (0.94) and GCS (0.95). GLS exhibited excellent ICC (0.99) in both intra- and
      interobserver variability analysis with very narrow limits of agreement (-0.6 to
      0.5 for intraobserver and -1.3 to 0.96 for interobserver agreement). Similarly,
      GCS showed excellent ICC (0.99) in both variability analyses with narrow limits
      of agreement (-1.1 to 1.2 for intraobserver and -1.7 to 1.3 for interobserver
      agreement), whereas LVEF showed larger limits of agreement (-14.4 to 10.1). The
      analysis of fast-SENC derived myocardial strain using cardiac MRI provides a
      highly reproducible method for assessing LV functional performance.

PMID- 30237412
TI  - Importance of integrity of cell-cell junctions for the mechanics of confluent
      MDCK II cells.
AB  - Intercellular junctions are important mechanical couplers between cells in
      epithelial layers providing adhesion and intercellular communication. Regulation
      of the junctions occurs in cellular processes such as layer formation, epithelial
      to-mesenchymal transition, embryogenesis, and cancer progression. Many studies
      addressed the role of force generation in cells for establishing lateral cell
      cell junctions and the role of cellular force transmission in tissue formation
      and maintenance. Our atomic force microscopy- (AFM) based study shed light on the
      role of both, tight junctions and adherens junctions for the mechanical
      properties of individual epithelial cells that are part of a confluent monolayer.
      We found that tight junctions are important for the establishment of a functional
      barrier-forming layer but impairing them does not reduce the mechanical integrity
      of cells. Depletion of ZO-1 results in a weak increase in cortical tension. An
      opposite effect was observed for disruption of E-cadherin-mediated adherens
      junctions using DTT. Opening of adherens junctions leads to substantial
      alterations of cellular mechanics such as reduced overall stiffness, but these
      changes turned out to be reversible after re-establishing disulfide bridges in E
      cadherin by removal of DTT. We found that regulatory mechanisms exist that
      preserve mechanical integrity during recovery of disrupted adherens junctions.

PMID- 30237413
TI  - Evidence for a maximum "shelf-life" of oocytes in mammals suggests that human
      menopause may be an implication of meiotic arrest.
AB  - There is an ongoing debate why a trait like human menopause should have evolved.
      Adaptive explanations explain menopause with fitness benefits of ceasing
      reproduction, whereas non-adaptive explanations view it as an epiphenomenon. Here
      we present data in support of non-adaptive explanations of menopause suggesting a
      maximum shelf-life of oocytes. By analyzing the association between lifespan and
      age at reproductive senescence across 49 mammal species, we find that the
      positive association levels off in long lived species, indicating that the age at
      reproductive senescence has an upper limit. Only in baleen whales there seems to
      be no evidence for reproductive senescence. We suggest that apart from the baleen
      whales, the confinement of reproductive senescence in long-lived species may be
      the result of physiological constraints imposed by the long period of time
      oocytes remain inactive in an arrested phase of meiosis from their production in
      utero until ovulation. We therefore conclude that menopause may be an implication
      of the long duration of meiotic arrest caused by semelgametogenesis together with
      long lifespan.

PMID- 30237414
TI  - A Cambrian unarmoured lobopodian, ?Lenisambulatrix humboldti gen. et sp. nov.,
      compared with new material of ?Diania cactiformis.
AB  - Cambrian marine lobopodians are generally considered as predecessors of modern
      panarthropods (onychophorans, tardigrades, and arthropods). Hence, further study
      of their morphological diversity and early radiation may enhance our
      understanding of the ground pattern and evolutionary history of panarthropods.
      Here, we report a rare lobopodian species, ?Lenisambulatrix humboldti gen. et sp.
      nov. ("Humboldt lobopodian"), from the early Cambrian Chengjiang Lagerstatte and
      describe new morphological features of ?Diania cactiformis, a coeval armoured
      lobopodian nicknamed "walking cactus". Both lobopodian species were similar in
      possessing rather thick, elongate lobopods without terminal claws. However, in
      contrast to ?Diania cactiformis, the body of which was heavily armored with
      spines, the trunk and limbs of the Humboldt lobopodian were entirely unarmored.
      Our study augments the morphological diversity of Cambrian lobopodians and
      presents two evolutionary extremes of cuticular ornamentation: one represented by
      the Humboldt lobopodian, which was most likely entirely "naked", the other
      epitomized by ?D. cactiformis, which was highly "armoured".

PMID- 30237416
TI  - Dynamical instability of the electric transport in superconductors.
AB  - We develop a nonlinear theory of the electronic transport in superconductors in
      the framework of the time-dependent Ginzburg-Landau (TDGL) equation. We utilize
      self-consistent Gaussian approximation and reveal the conditions under which the
      current-voltage V(I) dependence (I-V characteristics) acquires an S-shape form
      leading to switching instabilities. We demonstrate that in two-dimensions the
      emergence of such an instability is a hallmark of the Berezinskii-Kosterlitz
      Thouless (BKT) transition that we have detected by transport measurements of
      titanium nitride (TiN) films. Our theoretical findings compare favorably with our
      experimental results.

PMID- 30237415
TI  - Metabolite accumulation and metabolic network in developing roots of Rehmannia
      glutinosa reveals its root developmental mechanism and quality.
AB  - Rehmannia glutinosa root contains many compounds with important medicinal
      properties and nutritional benefits, but only more than 140 compounds have been
      reported so far. Many other compounds and their accumulation and metabolic
      networks during its development remain unclear. In order to clarify them, its
      metabolic profiles at three different developmental stages were analyzed using
      untargeted LC-MS analysis. Multivariate analysis revealed that 434 metabolites
      differently accumulated in its different stages, suggesting different change
      trends. The metabolites having the same trend share common metabolic pathways,
      the metabolites showing increasing contents during its development have medical
      and nutritional values, and some mature root-specific metabolites may be better
      candidates for its quality control; 434 metabolites were mapped onto 111 KEGG
      pathways including 62 enzymes, whose increasing and decreasing patterns were
      shown during its development. Some metabolites complicatedly interacted with some
      enzymes and the top-10 pathways enriched from 111 KEGG pathways in network
      analysis. These findings extended the dataset of its identified compounds, and
      revealed that its development and quality were associated with the accumulation
      of different metabolites. Our work will lay the foundation for the better
      understanding of its chemical constituents, quality and developmental mechanism.

PMID- 30237417
TI  - Liquid Marble Actuator for Microfluidic Logic Systems.
AB  - A mechanical flip-flop actuator has been developed that allows for the facile re
      routing and distribution of liquid marbles (LMs) in digital microfluidic devices.
      Shaped loosely like a triangle, the actuating switch pivots from one bistable
      position to another, being actuated by the very low mass and momentum of a LM
      rolling under gravity (~4 * 10-6 kg ms-1). The actuator was laser-cut from cast
      acrylic, held on a PTFE coated pivot, and used a PTFE washer. Due to the rocking
      motion of the switch, sequential LMs are distributed along different channels,
      allowing for sequential LMs to traverse parallel paths. This distributing effect
      can be easily cascaded, for example to evenly divide sequential LMs down four
      different paths. This lightweight, cheap and versatile actuator has been
      demonstrated in the design and construction of a LM-operated mechanical
      multiplication device - establishing its effectiveness. The actuator can be
      operated solely by gravity, giving it potential use in point-of-care devices in
      low resource areas.

PMID- 30237418
TI  - Let-7b attenuates cisplatin resistance and tumor growth in gastric cancer by
      targeting AURKB.
AB  - Platinum-based chemotherapy is currently a standard treatment strategy for
      patients with gastric cancer. Eventhough it has been widely shown that microRNAs
      (miRNAs) are involved in tumor development, whether miRNAs have a role in
      chemosensitivity of gastric cancer cells to platinum-based treatment remain
      largely undefined. In this study, a cisplatin-resistant gastric cancer cell line
      (SGC7901/DDP) with stable enhanced expression or knockdown of let-7b was
      generated. MTT and TUNEL assays were carried out to assess whether miR-let-7 is
      crucial for cell viability and apoptosis, respectively. In vitro luciferase
      reporter assay was performed to explore target genes of let-7b. Further, a
      subcutaneously transplanted tumor model in BALB/c nude mice was used to determine
      the impacts of let-7b on tumor growth in vivo. We observed that the let-7b
      expression level of SGC7901/DDP cells was significantly lower than for its
      parental SGC7901 cells. Transfection of let-7b mimics was found to increase the
      cytotoxicity of DDP to SGC7901/DDP cells by inducing apoptosis. However, reversed
      cytotoxicity of DDP was observed in SGC7901/DDP cells with knockdown of let-7b.
      Luciferase reporter assay indicated that let-7b targeted AURKB in SGC7901/DDP
      cells. Knockdown of AURKB imitated the effect of let-7b overexpression on the
      sensitivity of SGC7901/DDP cells to DDP. Further investigation demonstrated that
      the SGC7901/DDP primary tumor growth was significantly reduced by let-7b mimic
      transfection. These findings indicate that overexpression of let-7b might provide
      a potential strategic approach for attenuating DDP resistance in SGC7901/DDP
      human gastric cancer cells.

PMID- 30237419
TI  - Cryptic population structure reveals low dispersal in Iberian wolves.
AB  - Highly mobile mammalian carnivores are expected to have the capability to
      maintain high levels of gene flow across large geographic scales. Nonetheless,
      surprising levels of genetic structure have been found in many such populations.
      We combined genetic and spatial behavioural information from wolves (Canis lupus)
      in the Iberian Peninsula (Western Europe) during the last two decades to present
      a particular case of low dispersal levels in a large carnivore population
      persisting in human-dominated landscapes. We found an exceptionally reticulated
      pattern of cryptic population structure emerging at two hierarchical levels, in
      which four or eleven meaningful genetic clusters can be recognized, respectively.
      These clusters were characterized by moderate-high levels of differentiation
      (average pairwise FST = 0.09-0.19), low levels of admixture and varying degrees
      of genetic diversity. The number of dispersers identified among the 11 clusters
      was very low (<4% out of 218 wolves). Spatial information of tracked wolves
      further confirmed the geographical genetic patterns (only 2 out of 85 collared
      wolves overlapped with more than one genetic cluster). The high levels of genetic
      structure in this population may be determined by the recent demographic history
      of this population, among other factors. The identification of meaningful genetic
      clusters has implications for the delineation of conservation units and,
      consequently, on the conservation and management actions for Iberian wolves.

PMID- 30237421
TI  - Cyclin-dependent kinase 5-mediated phosphorylation of chloride intracellular
      channel 4 promotes oxidative stress-induced neuronal death.
AB  - Oxidative stress can cause apoptosis in neurons and may result in
      neurodegenerative diseases. However, the signaling mechanisms leading to
      oxidative stress-induced neuronal apoptosis are not fully understood. Oxidative
      stress stimulates aberrant activation of cyclin-dependent kinase 5 (CDK5),
      thought to promote neuronal apoptosis by phosphorylating many cell death-related
      substrates. Here, using protein pulldown methods, immunofluorescence experiments
      and in vitro kinase assays, we identified chloride intracellular channel 4
      (CLIC4), the expression of which increases during neuronal apoptosis, as a CDK5
      substrate. We found that activated CDK5 phosphorylated serine 108 in CLIC4,
      increasing CLIC4 protein stability, and accumulation. Pharmacological inhibition
      or shRNA-mediated silencing of CDK5 decreased CLIC4 levels in neurons. Moreover,
      CLIC4 overexpression led to neuronal apoptosis, whereas knockdown or
      pharmacological inhibition of CLIC4 attenuated H2O2-induced neuronal apoptosis.
      These results implied that CLIC4, by acting as a substrate of CDK5, mediated
      neuronal apoptosis induced by aberrant CDK5 activation. Targeting CLIC4 in
      neurons may therefore provide a therapeutic approach for managing progressive
      neurodegenerative diseases that arise from neuronal apoptosis.

PMID- 30237422
TI  - Balancing conservation and development in Winter Olympic construction: evidence
      from a multi-scale ecological suitability assessment.
AB  - Optimizing spatial patterns of land development and minimizing the ecological
      impact of concentrated construction is the key to realizing regionally
      sustainable development. The reasonable assessment of the ecological effects of
      the Winter Olympic construction on areas where the mountainous ecosystem is
      ecologically sensitive and vulnerable is urgent for responsible urban and
      regional development. Here, we assess the multi-scale suitability of ecologically
      compatible development in Winter Olympic regions using the ecological suitability
      assessment method based on GIS spatial analysis. We found the Chongli District
      had relatively high ecological structure and function resistances at a basin
      scale and that the towns where Olympic facilities located also had larger
      ecological resistance. The integrated suitability assessment showed the prior and
      moderate zones for suitable large-scale development and utilization in Chongli
      were smaller than those in other counties. The total loss area of natural
      ecological systems (forests, shrubs and meadows) for a new ski resort is 117.27
      hm2, which will lead to ecosystem function loss such as water and soil
      conservation and will potentially impact ecological systems. This research will
      be a useful reference for exploring the multi-scale balancing of conservation and
      development for Winter Olympic regions, and in turn, for concentrated global
      constructions.

PMID- 30237420
TI  - Frustrated endocytosis controls contractility-independent mechanotransduction at
      clathrin-coated structures.
AB  - It is generally assumed that cells interrogate the mechanical properties of their
      environment by pushing and pulling on the extracellular matrix (ECM). For
      instance, acto-myosin-dependent contraction forces exerted at focal adhesions
      (FAs) allow the cell to actively probe substrate elasticity. Here, we report that
      a subset of long-lived and flat clathrin-coated structures (CCSs), also termed
      plaques, are contractility-independent mechanosensitive signaling platforms. We
      observed that plaques assemble in response to increasing substrate rigidity and
      that this is independent of FAs, actin and myosin-II activity. We show that
      plaque assembly depends on alphavbeta5 integrin, and is a consequence of
      frustrated endocytosis whereby alphavbeta5 tightly engaged with the stiff
      substrate locally stalls CCS dynamics. We also report that plaques serve as
      platforms for receptor-dependent signaling and are required for increased Erk
      activation and cell proliferation on stiff environments. We conclude that CCSs
      are mechanotransduction structures that sense substrate rigidity independently of
      cell contractility.

PMID- 30237423
TI  - NADPH oxidase 4 regulates anoikis resistance of gastric cancer cells through the
      generation of reactive oxygen species and the induction of EGFR.
AB  - Anoikis is a type of programmed cell death induced by detachment from the
      extracellular matrix. In cancer cells, anoikis resistance is essential for cancer
      cell survival in blood circulation and distant metastasis. However, the
      mechanisms behind anoikis resistance of gastric cancer remain largely unknown.
      Herein, we demonstrate that NADPH oxidase 4 (NOX4) expression and reactive oxygen
      species (ROS) generation are upregulated in suspension gastric cell cultures
      compared with adherent cultures. Silencing of NOX4 decreases ROS generation and
      downregulates EGFR, sensitizing cells to anoikis. NOX4 overexpression upregulates
      ROS and EGFR levels and promotes anoikis resistance. NOX4 depletion inhibits
      gastric cancer survival in blood circulation and attenuates distant metastasis.
      NOX4 expression is correlated with EGFR expression in patients. In conclusion,
      induction of NOX4 expression by detachment promotes anoikis resistance of gastric
      cancer through ROS generation and downstream upregulation of EGFR, which is
      critical for the metastatic progression of gastric cancer.

PMID- 30237425
TI  - Effective surface conductivity of optical hyperbolic metasurfaces: from far-field
      characterization to surface wave analysis.
AB  - Metasurfaces offer great potential to control near- and far-fields through
      engineering optical properties of elementary cells or meta-atoms. Such
      perspective opens a route to efficient manipulation of the optical signals both
      at nanoscale and in photonics applications. In this paper we show that a local
      surface conductivity tensor well describes optical properties of a resonant
      plasmonic hyperbolic metasurface both in the far-field and in the near-field
      regimes, where spatial dispersion usually plays a crucial role. We retrieve the
      effective surface conductivity tensor from the comparative analysis of
      experimental and numerical reflectance spectra of a metasurface composed of
      elliptical gold nanoparticles. Afterwards, the restored conductivities are
      validated by semi-analytic parameters obtained with the nonlocal discrete dipole
      model with and without interaction contribution between meta-atoms. The effective
      parameters are further used for the dispersion analysis of surface plasmons
      localized at the metasurface. The obtained effective conductivity describes
      correctly the dispersion law of both quasi-TE and quasi-TM plasmons in a wide
      range of optical frequencies as well as the peculiarities of their propagation
      regimes, in particular, topological transition from the elliptical to hyperbolic
      regime with eligible accuracy. The analysis in question offers a simple practical
      way to describe properties of metasurfaces including ones in the near-field zone
      with effective conductivity tensor extracting from the convenient far-field
      characterization.

PMID- 30237427
TI  - Endocarditis: oral versus intravenous antibiotics.

PMID- 30237426
TI  - Plasmon-induced hot electron transfer in AgNW@TiO2@AuNPs nanostructures.
AB  - Compared to the limited absorption cross-section of conventional photoactive TiO2
      nanoparticles (NPs), plasmonic metallic nanoparticles can efficiently convert
      photons from an extended spectrum range into energetic carriers because of the
      localized surface plasmon resonance (LSPR). Using these metal oxide
      semiconductors as shells for plasmonic nanoparticles (PNPs) that absorb visible
      light could extend their applications. The photophysics of such systems is
      performed using transient absorption measurements and steady extinction
      simulations and shows that the plasmonic energy transfer from the AgNWs core to
      the TiO2 shell results from a hot carrier injection process. Lifetimes obtained
      from photobleaching decay dynamics suggest that (i) the presence of gold
      nanoparticles (AuNPs) in AgNWs@TiO2@AuNPs systems can further promote the hot
      carrier transfer process via plasmonic coupling effects and (ii) the carrier
      dynamics is greatly affected by the shell thickness of TiO2. This result points
      out a definite direction to design appropriate nanostructures with tunable charge
      transfer processes toward photo-induced energy conversion applications.

PMID- 30237428
TI  - Drug-coated balloons - another option for small-vessel disease.

PMID- 30237429
TI  - Aspirin for primary prevention of CVD: a matter of balance.

PMID- 30237424
TI  - Bi-directional genetic modulation of GSK-3beta exacerbates hippocampal
      neuropathology in experimental status epilepticus.
AB  - Glycogen synthase kinase-3 (GSK-3) is ubiquitously expressed throughout the brain
      and involved in vital molecular pathways such as cell survival and synaptic
      reorganization and has emerged as a potential drug target for brain diseases. A
      causal role for GSK-3, in particular the brain-enriched GSK-3beta isoform, has
      been demonstrated in neurodegenerative diseases such as Alzheimer's and
      Huntington's, and in psychiatric diseases. Recent studies have also linked GSK-3
      dysregulation to neuropathological outcomes in epilepsy. To date, however, there
      has been no genetic evidence for the involvement of GSK-3 in seizure-induced
      pathology. Status epilepticus (prolonged, damaging seizure) was induced via a
      microinjection of kainic acid into the amygdala of mice. Studies were conducted
      using two transgenic mouse lines: a neuron-specific GSK-3beta overexpression and
      a neuron-specific dominant-negative GSK-3beta (GSK-3beta-DN) expression in order
      to determine the effects of increased or decreased GSK-3beta activity,
      respectively, on seizures and attendant pathological changes in the hippocampus.
      GSK-3 inhibitors were also employed to support the genetic approach. Status
      epilepticus resulted in a spatiotemporal regulation of GSK-3 expression and
      activity in the hippocampus, with decreased GSK-3 activity evident in non-damaged
      hippocampal areas. Consistent with this, overexpression of GSK-3beta exacerbated
      status epilepticus-induced neurodegeneration in mice. Surprisingly, decreasing
      GSK-3 activity, either via overexpression of GSK-3beta-DN or through the use of
      specific GSK-3 inhibitors, also exacerbated hippocampal damage and increased
      seizure severity during status epilepticus. In conclusion, our results
      demonstrate that the brain has limited tolerance for modulation of GSK-3 activity
      in the setting of epileptic brain injury. These findings caution against
      targeting GSK-3 as a treatment strategy for epilepsy or other neurologic
      disorders where neuronal hyperexcitability is an underlying pathomechanism.

PMID- 30237430
TI  - Revealing of Core Shell Effect on Frequency-Dependent Properties of Bi-based
      Relaxor/Ferroelectric Ceramic Composites.
AB  - In this study, electromechanical characteristics of (1-x) Bi0.5Na0.5TiO3-xSrTiO3
      (ST26, x = 0.26)/(1-y) Bi0.5Na0.5TiO3-ySrTiO3 (ST10, y = 0.1) (matrix/seed)
      composites were studied. The ST26 (high relaxor phase) and ST10 (a relaxor
      ferroelectric (RF), high ferroelectric phase) composite with large (r-ST26-ST10)
      and small (t-ST26-ST10) grains exhibited frequency-related dielectric properties
      and large strain response at a low triggering electric field (an incipient
      piezoelectricity). It is ascribed to a matrix-seed effect originating from the
      inhomogeneous composition due to the presence of two phases. The r-ST26-ST10
      composite sintered at 4 h, prominent material, showed a high normalized dynamic
      strain (d33*) of ~700 pm/V (large grains) with stable frequency dependence
      properties at a low field of 40 kV/cm. The properties of the r-ST26-ST10
      composite exhibit less decay with frequency-related polarization and strain
      compared to those of t-ST26-ST10 composite. The increase in soaking time promotes
      the diffusion and homogenization of the microstructure in composites, leading to
      changes in the core-shell structure in the solid solution. The polarization and
      strain of the ST26-ST10 composites with the frequency are linked to the stability
      of the internal random fields created by non-ergodic relaxor phase of seed and
      the amount of phase change in the ergodic relaxor matrix.

PMID- 30237432
TI  - The Optimal Blood Pressure Target in Different Dialysis Populations.
AB  - Hypertension is common and contributes to adverse outcomes in patients undergoing
      dialysis. However, the proper blood pressure (BP) target remains controversial
      and several factors make this difficult. This study aimed to investigate the
      adequate BP target in patients undergoing prevalent dialysis. Data were retrieved
      from the Clinical Research Center for End-Stage Renal Disease (2009-2014). 2,299
      patients undergoing dialysis were evaluated. Patients were assigned into eight
      groups according to predialysis systolic blood pressure (SBP). The primary
      outcome was all-cause mortality. During the median follow-up of 4.5 years, a U
      shape relation between SBP and mortality was found. The risk of mortality was
      increased in the SBP <110 and >=170 mmHg groups. In subgroup analysis, the risk
      of mortality was similarly shown U-shape with SBP in subjects with no
      comorbidities, and no use of antihypertensive agents. However, only lowest SBP
      was a risk factor for mortality in patients with older, having diabetes or
      coronary artery disease, whereas highest SBP was an only risk factor in younger
      patients. In respect of dialysis characteristics, patients undergoing
      hemodialysis showed U-shape between SBP and mortality, while patients undergoing
      peritoneal dialysis did not. Among hemodialysis patients, patients with shorter
      dialysis vintage and less interdialytic weight gain showed U-shape association
      between SBP and mortality. This study showed that the lowest or highest SBP group
      had higher risk of mortality. Nevertheless, the optimal target BP should be
      applied according to individual condition of each patient.

PMID- 30237431
TI  - Barriers to Lynch Syndrome Testing and Preoperative Result Availability in Early
      onset Colorectal Cancer: A National Physician Survey Study.
AB  - OBJECTIVE: Although widely recommended, Lynch syndrome (LS) testing with tumor
      microsatellite instability (MSI) and/or immunohistochemistry (IHC) is
      infrequently performed in early-onset colorectal cancer (CRC), and CRC generally.
      Reasons are poorly understood. Hence, we conducted a national survey focusing on
      gastroenterologists, as they are frequently first to diagnose CRC, assessing
      testing barriers and which specialist is felt responsible for ordering MSI/IHC.
      Additionally, we assessed factors influencing timing of MSI/IHC ordering; testing
      on colonoscopy biopsy, opposed to post-operative surgical specimens, assists
      decisions on preoperative germline genetic testing and extent of colonic
      resection (ECR). METHODS: A 21-question web-based survey was distributed through
      an American College of Gastroenterology email listing. RESULTS: In total 509
      completed the survey. 442 confirmed gastroenterologists were analyzed. Only 33.4%
      felt gastroenterologists were responsible for MSI/IHC ordering; pathologists were
      believed most responsible (38.6%). Cost, unfamiliarity interpreting results and
      unavailable genetic counseling most commonly prevented routine ordering (33.3%,
      29.2%, 24.9%, respectively). In multivariable analysis, non-academic and rural
      settings were associated with cost and genetic counseling barriers. Only 46.1%
      felt MSI/IHC should always be performed on colonoscopy biopsy. Guideline
      familiarity predicted whether respondents felt surgical resection should be
      delayed until results returned given potential effect on ECR decisions.
      CONCLUSION: Inconsistencies in who is felt should order MSI/IHC may lead to
      diffusion of responsibility, preventing consistent testing, including
      preoperatively. Assuring institutional universal testing protocols are in place,
      with focus on timing of testing, can optimize care. Strategies addressing cost
      barriers and genomic service availability in rural and non-academic settings can
      enhance testing. Greater emphasis on guideline familiarity is required.

PMID- 30237433
TI  - Expanding the concept of peroxisomal diseases and efficient diagnostic system in
      Japan.
AB  - The concept of peroxisomal diseases is expanding because of improvements in
      diagnostic technology based on advanced biochemical analysis and development of
      next-generation sequencing. For quicker and more accurate diagnosis of as many
      patients as possible, we developed a new diagnostic system combining the
      conventional diagnostic system and comprehensive mutational analysis by whole
      exome sequencing in Japan. Adrenoleukodystrophy (ALD) is the most common
      peroxisomal disease. In the cerebral type of ALD, hematopoietic stem cell
      transplantation is the only treatment in the early stage, and thus prompt
      diagnosis will improve the prognosis of affected patients. Furthermore, it is
      also important to identify pre-symptomatic patients by family analysis of
      probands by providing appropriate disease information and genetic counseling,
      which will also lead to early intervention. Here, we summarize current
      information related to peroxisomal diseases and ALD and introduce our efficient
      diagnostic system for use in Japan, which resulted in the diagnosis of 73
      Japanese patients with peroxisome biogenesis disorders, 16 with impaired beta
      oxidation of fatty acids, three with impaired etherphospholipid biosynthesis, and
      191 Japanese families with ALD so far.

PMID- 30237434
TI  - Author Correction: Molecular architecture of the multifunctional collagen lysyl
      hydroxylase and glycosyltransferase LH3.
AB  - The previously published version of this Article contained an error in Figure 3.
      In panel a, the residues His667 and Asp669 were incorrectly labelled as His627
      and Asp629. The error has been corrected in both the PDF and HTML versions of the
      Article.

PMID- 30237436
TI  - Acylated-acyl carrier protein stabilizes the Pseudomonas aeruginosa WaaP
      lipopolysaccharide heptose kinase.
AB  - Phosphorylation of Pseudomonas aeruginosa lipopolysaccharide (LPS) is important
      for maintaining outer membrane integrity and intrinsic antibiotic resistance. We
      solved the crystal structure of the LPS heptose kinase WaaP, which is essential
      for growth of P. aeruginosa. WaaP was structurally similar to eukaryotic protein
      kinases and, intriguingly, was complexed with acylated-acyl carrier protein (acyl
      ACP). WaaP produced by in vitro transcription-translation was insoluble unless
      acyl-ACP was present. WaaP variants designed to perturb the acyl-ACP interaction
      were less stable in cells and exhibited reduced kinase function. Mass
      spectrometry identified myristyl-ACP as the likely physiological binding partner
      for WaaP in P. aeruginosa. Together, these results demonstrate that acyl-ACP is
      required for WaaP protein solubility and kinase function. To the best of our
      knowledge, this is the first report describing acyl-ACP in the role of a cofactor
      necessary for the production and stability of a protein partner.

PMID- 30237435
TI  - LncRNA SNHG15 acts as a ceRNA to regulate YAP1-Hippo signaling pathway by
      sponging miR-200a-3p in papillary thyroid carcinoma.
AB  - Over the past decade, lncRNAs have been widely reported in human malignant
      tumors, including papillary thyroid carcinoma. LncRNA SNHG15 has been validated
      to be a tumor facilitator in several types of malignancies. The present study
      focused on the biological role of SNHG15 in papillary thyroid carcinoma. Based on
      the result of qPCR analysis, we identified the strong expression of SNHG15 in
      human papillary thyroid carcinoma tissues and cell lines. Moreover, Kaplan-Meier
      method was utilized to analyze the internal relevance between SNHG15 expression
      and overall survival rate of patients with papillary thyroid carcinoma. Loss-of
      function assays were designed and conducted to determine the inhibitory effects
      of silenced SNHG15 on the cell growth and migration in papillary thyroid
      carcinoma. The mechanical investigation indicated that SNHG15 upregulated YAP1 by
      sponging miR-200a-3p. Moreover, results of gain-of-function assays validated the
      anti-oncogenic function of miR-200a-3p in papillary thyroid carcinoma. Finally,
      results of rescue assays validated the function of SNHG15-miR-200a-3p-YAP1 axis
      in papillary thyroid carcinoma. YAP1 is known as an oncogene and a core factor of
      Hippo pathway. Here, we demonstrated that SNHG15 inactivated Hippo signaling
      pathway in papillary thyroid carcinoma. In summary, our findings demonstrated
      that SNHG15 serves as a competitively endogenous RNA (ceRNA) to regulate YAP1
      Hippo signaling pathway by sponging miR-200a-3p in papillary thyroid carcinoma.

PMID- 30237438
TI  - Artificial Light at Night Affects Emergence from a Refuge and Space Use in
      Guppies.
AB  - Artificial light at night (ALAN) is a major form of anthropogenic pollution. ALAN
      is well known to affect different behaviours during nighttime, when changes in
      light conditions often have immediate consequences for the trade-offs individuals
      experience. How ALAN affects daytime behaviours, however, has received far less
      attention. Here we studied how ALAN affected daytime personality traits and
      learning ability. We exposed Trinidadian guppies, Poecilia reticulata, for 10
      weeks to different ALAN levels: bright light (24 hrs bright light, ~5,000 lx),
      dim light (12 hrs bright light; 12 hrs dim light, ~0.5 lx) and control (12 hrs
      bright light; 12 hrs dark). Afterwards, we tested how the treatments affected
      diurnal emergence from a refuge, space use, activity, sociability and the ability
      to memorize the location of companion fish. Individuals exposed to the light
      treatments (both dim and bright light) emerged quicker from a refuge and fish
      from the bright light treatment spent relatively more time in the open area of
      the arena. ALAN did not affect any of the other behaviours, although memory could
      not be tested since fish did not learn the companions' location. Our results
      demonstrate that ALAN, next to affecting nocturnal behaviours, can also affect
      key diurnal behavioural processes, associated with risk-taking.

PMID- 30237437
TI  - Lung colonization by Aspergillus fumigatus is controlled by ZNF77.
AB  - Aspergillus fumigatus is a critical pathogen of humans. Exposure to A. fumigatus
      conidia occurs frequently but is normally cleared from the respiratory airways.
      In contrast, individuals with respiratory diseases are often highly colonized by
      fungi. Here, we use genome-edited epithelial cells to show that the genetic
      variant rs35699176 in ZNF77 causes loss of integrity of the bronchial epithelium
      and increases levels of extracellular matrix proteins. These changes promote A.
      fumigatus conidial adhesion, germination and growth. RNA-seq and LC/MS-MS
      analysis reveal rs35699176 upregulates vesicle trafficking leading to an
      increment of adhesion proteins. These changes make cells carrying rs35699176 more
      receptive to A. fumigatus in the early stages of infection. Moreover, patients
      with fungal asthma carrying rs35699176+/- have higher A. fumigatus loads in their
      respiratory airway. Our results indicate ZNF77 as a key controller of Aspergillus
      colonization and suggest its utility as a risk-marker for patient stratification.

PMID- 30237439
TI  - Development of a yeast-based system to identify new hBRAFV600E functional
      interactors.
AB  - BRAFV600E is a mutant Ser-Thr protein kinase that plays a crucial role in many
      types of cancer, including melanoma. Despite several aspects of BRAFV600E biology
      have been already elucidated, the proteins that regulate its expression and
      activity remain largely unknown, hampering our capacity to control its
      unrestrained effects. Here, we propose yeast Saccharomyces cerevisiae as a model
      system that can be used to achieve a better understanding of the regulation of
      human BRAFV600E.By showing that in osmotic stress conditions hBRAFV600E can
      rescue the growth of strains carrying a double or triple deletion in MAPKKK
      belonging to the HOG pathway, we demonstrate that this oncogenic kinase is active
      in yeast even if it does not have an ortholog. Moreover, we report that, in the
      yeast ptp3?ptc1? strain that is deleted in the genes encoding for two
      phosphatases responsible for Hog1 de-phoshorylation, hBRAFV600E mimics the
      toxicity observed in the presence of constitutive Hog1 activation. Finally, we
      exploit such a toxicity to perform a functional screening of a human cDNA
      library, looking for cDNAs able to rescue yeast growth. In this way, we identify
      SMIM10, a mitochondrial protein that in melanoma cells selectively downregulates
      BRAFV600E RNA and protein levels, by acting indirectly at the post
      transcriptional level. Upon SMIM10 overexpression, BRAFV600E melanoma cells show
      disrupted mitochondrial structure/function and undergo senescence. They also show
      decreased ability to proliferate and form colonies, as well as increased
      sensitivity to the BRAF inhibitor vemurafenib. Interestingly, the analysis of
      TCGA melanoma samples indicates that patients with higher SMIM10 levels have a
      better prognosis. Therefore, these data suggest that SMIM10 exerts an
      oncosuppressive role in melanoma cells.Taken together, our results unveil the
      potential of S. cerevisiae to study hBRAFV600E, to populate the network of its
      functional interactors and, in doing so, to uncover new cancer-associated genes
      with therapeutic potential.

PMID- 30237440
TI  - A reciprocal feedback between the PDZ binding kinase and androgen receptor drives
      prostate cancer.
AB  - Elucidation of mechanisms underlying the increased androgen receptor (AR)
      activity and subsequent development of aggressive prostate cancer (PrCa) is
      pivotal in developing new therapies. Using a systems biology approach, we
      interrogated the AR-regulated proteome and identified PDZ binding kinase (PBK) as
      a novel AR-regulated protein that regulates full-length AR and AR variants (ARVs)
      activity in PrCa. PBK overexpression in aggressive PrCa is associated with early
      biochemical relapse and poor clinical outcome. In addition to its carboxy
      terminus ligand-binding domain, PBK directly interacts with the amino terminus
      transactivation domain of the AR to stabilise it thereby leading to increased AR
      protein expression observed in PrCa. Transcriptome sequencing revealed that PBK
      is a mediator of global AR signalling with key roles in regulating tumour
      invasion and metastasis. PBK inhibition decreased growth of PrCa cell lines and
      clinical specimen cultured ex vivo. We uncovered a novel interplay between AR and
      PBK that results in increased AR and ARVs expression that executes AR-mediated
      growth and progression of PrCa, with implications for the development of PBK
      inhibitors for the treatment of aggressive PrCa.

PMID- 30237442
TI  - Walking in orthostatic tremor modulates tremor features and is characterized by
      impaired gait stability.
AB  - Primary orthostatic tremor (OT) is characterized by high-frequency lower-limb
      muscle contractions and a disabling sense of unsteadiness while standing.
      Patients consistently report a relief of symptoms when starting to ambulate.
      Here, we systematically examined and linked tremor and gait characteristics in
      patients with OT. Tremor and gait features were examined in nine OT patients and
      controls on a pressure-sensitive treadmill for one minute of walking framed by
      two one-minute periods of standing. Tremor characteristics were assessed by time
      frequency analysis of surface EMG-recordings from four leg muscles. High
      frequency tremor during standing (15.29 +/- 0.17 Hz) persisted while walking but
      was consistently reset to higher frequencies (16.34 +/- 0.25 Hz; p < 0.001).
      Tremor intensity was phase-dependently modulated, being predominantly observable
      during stance phases (p < 0.001). Tremor intensity scaled with the force applied
      during stepping (p < 0.001) and was linked to specific gait alterations, i.e.,
      wide base walking (p = 0.019) and increased stride-to-stride fluctuations (p =
      0.002). OT during walking persists but is reset to higher frequencies, indicating
      the involvement of supraspinal locomotor centers in the generation of OT rhythm.
      Tremor intensity is modulated during the gait cycle, pointing at specific
      pathways mediating the peripheral manifestation of OT. Finally, OT during walking
      is linked to gait alterations resembling a cerebellar and/or sensory ataxic gait
      disorder.

PMID- 30237441
TI  - Vegetation response to exceptional global warmth during Oceanic Anoxic Event 2.
AB  - The Cenomanian-Turonian Oceanic Anoxic Event (OAE2; ~94.5 million years ago)
      represents an episode of global-scale marine anoxia and biotic turnover, which
      corresponds to one of the warmest time intervals in the Phanerozoic. Despite its
      global significance, information on continental ecosystem response to this
      greenhouse episode is lacking. Here we present a terrestrial palynological record
      combined with marine-derived temperature data (TEX86) across an expanded OAE2
      section from the Southern Provencal Basin, France. Despite high TEX86-derived
      temperature estimates reaching up to 38  degrees C, the continental hinterland
      did support a diverse vegetation, adapted to persist under elevated temperatures.
      A transient phase of climatic instability and cooling during OAE2 known as Plenus
      Cold Event (PCE) is marked by the proliferation of open, savanna-type vegetation
      rich in angiosperms at the expanse of conifer-dominated forest ecosystems. A rise
      in early representatives of Normapolles-type pollen during the PCE marks the
      initial radiation of this important angiosperm group.

PMID- 30237443
TI  - ASK1 inhibition shows potential in DKD.

PMID- 30237444
TI  - Yellowstone Hot Springs are Organic Chemodiversity Hot Spots.
AB  - Yellowstone National Park hydrothermal springs were investigated according to
      their organic geochemistry with a special focus on the Yellowstone hot spring
      dissolved organic matter (YDOM) that was solid-phase extracted. Here we show that
      YDOM has a unique chemodiversity that has not yet been observed anywhere else in
      aquatic surface environments and that Yellowstone hot springs are organic
      chemodiversity hot spots. Four main geochemically classified hot spring types
      (alkaline-chloride, mixed alkaline-chloride, acid-chloride-sulfate and travertine
      precipitating) exhibited distinct organic molecular signatures that correlated
      remarkably well with the known inorganic geochemistry and manifested themselves
      in excitation emission matrix fluorescence, nuclear magnetic resonance, and
      ultrahigh resolution mass spectra. YDOM contained thousands of molecular formulas
      unique to Yellowstone of which 80% contained sulfur, even in low hydrogen sulfide
      containing alkaline-chloride springs. This unique YDOM reflects the extreme
      organic geochemistry present in the hydrothermal features of Yellowstone National
      Park.

PMID- 30237445
TI  - Author Correction: The rate of meiotic gene conversion varies by sex and age.
AB  - In the version of this article published, statements about the impact of
      insertions and deletions on gene conversions were incorrect. We reported a bias
      toward deletions, whereas in fact the bias was toward insertions. We are deeply
      indebted to Laurent Duret and Brice Letcher for noticing this mistake in our
      manuscript. The following statements are incorrect in the published manuscript.

PMID- 30237446
TI  - Eicosapantaenoic acid treatment based on the EPA/AA ratio in patients with
      coronary artery disease: follow-up data from the Tochigi Ryomo EPA/AA Trial in
      Coronary Artery Disease (TREAT-CAD) study.
AB  - Eicosapentaenoic acid (EPA) administration has been reported to decrease the
      incidence of cardiovascular events, and the serum EPA/arachidonic acid (AA) ratio
      has been identified as a potential new risk marker for coronary artery disease
      (CAD). The present study aimed to investigate the value of EPA treatment based on
      the EPA/AA ratio at baseline. We retrospectively analyzed clinical outcome data
      from 149 CAD patients with a baseline EPA/AA ratio <= 0.4 who had received
      purified EPA (EPA group) or not (no EPA group) and CAD patients with an EPA/AA
      ratio > 0.4 who had not received EPA (control group). The baseline EPA/AA ratios
      were similar in the EPA and no EPA groups and were significantly lower than those
      in the control group (P < 0.0001). The EPA/AA ratio significantly increased in
      the EPA group (P < 0.0001) and the no EPA group (P < 0.001) but not in the
      control group. The cumulative incidence of cardiovascular death tended to be
      lower in the EPA group (log-rank test: P = 0.07). Receiver operating
      characteristic curve analysis demonstrated that the cut-off value of the target
      EPA/AA ratio after EPA treatment for all-cause death was 1.23 (AUC = 0.85, P =
      0.016). These results suggest that EPA treatment may improve the long-term
      prognosis in CAD patients with an EPA/AA ratio <= 0.4 and that an EPA/AA ratio >
      1.2 may be an appropriate EPA treatment target value to reduce mortality.

PMID- 30237447
TI  - DNA-based memory devices for recording cellular events.
AB  - Measuring biological data across time and space is critical for understanding
      complex biological processes and for various biosurveillance applications.
      However, such data are often inaccessible or difficult to directly obtain. Less
      invasive, more robust and higher-throughput biological recording tools are needed
      to profile cells and their environments. DNA-based cellular recording is an
      emerging and powerful framework for tracking intracellular and extracellular
      biological events over time across living cells and populations. Here, we review
      and assess DNA recorders that utilize CRISPR nucleases, integrases and base
      editing strategies, as well as recombinase and polymerase-based methods.
      Quantitative characterization, modelling and evaluation of these DNA-recording
      modalities can guide their design and implementation for specific application
      areas.

PMID- 30237448
TI  - Anomalous behavior of membrane fluidity caused by copper-copper bond coupled
      phospholipids.
AB  - Membrane fluidity, essential for cell functions, is obviously affected by copper,
      but the molecular mechanism is poorly understood. Here, we unexpectedly observed
      that a decrease in phospholipid (PL) bilayer fluidity caused by Cu2+ was more
      significant than those by Zn2+ and Ca2+, while a comparable reduction occurred in
      the last two ions. This finding disagrees with the placement in the periodic
      table of Cu just next to Zn and far from Ca. The physical nature was revealed to
      be an anomalous attraction between Cu+ cations, as well as the induced motif of
      two phospholipids coupled by Cu-Cu bond (PL-diCu-PL). Namely, upon Cu2+ ion
      binding to a negatively charged phosphate group of lipid, Cu2+ was reduced to
      Cu+. The attraction of the cations then caused one Cu+ ion simultaneously binding
      to two lipids and another Cu+, resulting in the formation of PL-diCu-PL
      structure. In contrast, this attraction cannot occur in the cases of Zn and Ca
      ions. Remarkably, besides lipids, the phosphate group also widely exists in other
      biological molecules, including DNA, RNA, ADP and ATP. Our findings thus provide
      a new view for understanding the biological functions of copper and the mechanism
      underlying copper-related diseases, as well as lipid assembly.

PMID- 30237449
TI  - Robust single-cell DNA methylome profiling with snmC-seq2.
AB  - Single-cell DNA methylome profiling has enabled the study of epigenomic
      heterogeneity in complex tissues and during cellular reprogramming. However,
      broader applications of the method have been impeded by the modest quality of
      sequencing libraries. Here we report snmC-seq2, which provides improved read
      mapping, reduced artifactual reads, enhanced throughput, as well as increased
      library complexity and coverage uniformity compared to snmC-seq. snmC-seq2 is an
      efficient strategy suited for large-scale single-cell epigenomic studies.

PMID- 30237450
TI  - Facile reduction of graphene oxide suspensions and films using glass wafers.
AB  - This paper reports a facile and green method for conversion of graphene oxide
      (GO) into graphene by low-temperature heating (80  degrees C) in the presence of
      a glass wafer. Compared to conventional GO chemical reduction methods, the
      presented approach is easy-scalable, operationally simple, and based on the use
      of a non-toxic recyclable deoxygenation agent. The efficiency of the proposed
      method is further expanded by the fact that it can be applied for reducing both
      GO suspensions and large-scale thin films formed on various substrates prior to
      the reduction process. The quality of the obtained reduced graphene oxide (rGO)
      strongly depends on the type of the used glass wafer, and, particularly,
      magnesium silicate glass can provide rGO with the C/O ratio of 7.4 and
      conductivity of up to 33000 S*cm-1. Based on the data obtained, we have suggested
      a mechanism of the observed reduction process in terms of the hydrolysis of the
      glass wafer with subsequent interaction of the leached alkali and alkali earth
      cations and silicate anions with graphene oxide, resulting in elimination of the
      oxygen-containing groups from the latter one. The proposed approach can be
      efficiently used for low-cost bulk-quantity production of graphene and graphene
      based materials for a wide field of applications.

PMID- 30237451
TI  - Cancer immunotherapy: When a CAR becomes a tank.

PMID- 30237452
TI  - Neurodegenerative diseases: Ropin' in ALS.

PMID- 30237453
TI  - Genetic disorders: Bacterial therapeutic steps into the breach.

PMID- 30237455
TI  - Ageing: Reversing muscle degeneration.

PMID- 30237456
TI  - The effect of serum triglyceride concentration on the outcome of acute
      pancreatitis: systematic review and meta-analysis.
AB  - Elevated serum triglyceride concentration (seTG, >1.7 mM or >150 mg/dL) or in
      other words hypertriglyceridemia (HTG) is common in the populations of developed
      countries. This condition is accompanied by an increased risk for various
      diseases, such as acute pancreatitis (AP). It has been proposed that HTG could
      also worsen the course of AP. Therefore, in this meta-analysis, we aimed to
      compare the effects of various seTGs on the severity, mortality, local and
      systemic complications of AP, and on intensive care unit admission. 16 eligible
      studies, including 11,965 patients were retrieved from PubMed and Embase. The
      results showed that HTG significantly elevated the odds ratio (OR = 1.72) for
      severe AP when compared to patients with normal seTG (<1.7 mM). Furthermore, a
      significantly higher occurrence of pancreatic necrosis, persistent organ failure
      and renal failure was observed in groups with HTG. The rates of complications and
      mortality for AP were significantly increased in patients with seTG >5.6 mM or
      >11.3 mM versus <5.6 mM or <11.3 mM, respectively. We conclude that the presence
      of HTG worsens the course and outcome of AP, but we found no significant
      difference in AP severity based on the extent of HTG.

PMID- 30237457
TI  - Poldip2 knockdown inhibits vascular smooth muscle proliferation and neointima
      formation by regulating the expression of PCNA and p21.
AB  - Polymerase delta-interacting protein 2 (Poldip2) is a multi-functional protein
      with numerous roles in the vasculature, including the regulation of cell
      apoptosis and migration, as well as extracellular matrix deposition; however, its
      role in VSMC proliferation and neointimal formation is unknown. In this study, we
      investigated the role of Poldip2 in intraluminal wire-injury induced neointima
      formation and proliferation of vascular smooth muscle cells in vitro and in vivo.
      Poldip2 expression was observed in the intima and media of human atherosclerotic
      arteries, where it colocalized with proliferating cell nuclear antigen (PCNA).
      Wire injury of femoral arteries of Poldip2+/+ mice induced robust neointimal
      formation after 2 weeks, which was impaired in Poldip2+/- mice. PCNA expression
      was significantly reduced and expression of the cell cycle inhibitor p21 was
      significantly increased in wire-injured arteries of Poldip2+/- animals compared
      to wild-type controls. No difference was observed in apoptosis. Downregulation of
      Poldip2 in rat aortic smooth muscle cells significantly reduced serum-induced
      proliferation and PCNA expression, but upregulated p21 expression. Downregulation
      of p21 using siRNA reversed the inhibition of proliferation induced by knockdown
      of Poldip2. These results indicate that Poldip2 plays a critical role in the
      proliferation of VSMCs.

PMID- 30237458
TI  - Author Correction: Disturbed retrieval network and prospective memory decline in
      postpartum women.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30237459
TI  - Biosafety assessment of water samples from Wanzhou watershed of Yangtze Three
      Gorges Reservior in the quiet season in Caenorhabditis elegans.
AB  - We here employed a model animal of Caenorhabditis elegans to perform toxicity
      assessment of original surface water samples collected from Three Gorges
      Reservoir (TGR) in the quiet season in Wanzhou, Chongqing. Using some sublethal
      endpoints, including lifespan, body length, locomotion behavior, brood size, and
      intestinal reactive oxygen species (ROS) induction, we found that the examined
      five original surface water samples could not cause toxicity on wild-type
      nematodes. Nevertheless, the surface water sample collected from backwater area
      induced the significant increase in expressions of genes (sod-2 and sod-3)
      encoding Mn-SODs in wild-type nematodes. Among the examined five original surface
      water samples, exposure to the original surface water sample collected from
      backwater area could further cause the toxicity in decreasing locomotion behavior
      and in inducing intestinal ROS production in sod-3 mutant nematodes. Moreover,
      the solid phase of surface water sample collected from backwater area might
      mainly contribute to the observed toxicity in sod-3 mutant nematodes. Our results
      are helpful for understanding the potential effects of surface water in the TGR
      region in the quiet season on environmental organisms.

PMID- 30237460
TI  - A quantitative analysis of 3D-cell distribution in regenerating muscle-skeletal
      system with synchrotron X-ray computed microtomography.
AB  - One of the greatest enigmas of modern biology is how the geometry of muscular and
      skeletal structures are created and how their development is controlled during
      growth and regeneration. Scaling and shaping of vertebrate muscles and skeletal
      elements has always been enigmatic and required an advanced technical level in
      order to analyse the cell distribution in 3D. In this work, synchrotron X-ray
      computed microtomography (uCT) and chemical contrasting has been exploited for a
      quantitative analysis of the 3D-cell distribution in tissues of a developing
      salamander (Pleurodeles waltl) limb - a key model organism for vertebrate
      regeneration studies. We mapped the limb muscles, their size and shape as well as
      the number and density of cells within the extracellular matrix of the developing
      cartilage. By using tomographic approach, we explored the polarity of the cells
      in 3D, in relation to the structure of developing joints. We found that the
      polarity of chondrocytes correlates with the planes in joint surfaces and also
      changes along the length of the cartilaginous elements. Our approach generates
      data for the precise computer simulations of muscle-skeletal regeneration using
      cell dynamics models, which is necessary for the understanding how anisotropic
      growth results in the precise shapes of skeletal structures.

PMID- 30237461
TI  - Transcriptome Sequencing and Metabolism Analysis Reveals the role of Cyanidin
      Metabolism in Dark-red Onion (Allium cepa L.) Bulbs.
AB  - Onion (Allium cepa L.) is an important bulbous vegetable crop that possesses
      important properties related to health as well as extraordinary colors. Naturally
      white onion bulbs were used in this study to reveal the complex metabolic
      mechanisms that underlie phenotypic traits, especially bulb pigmentation. Six
      libraries (three dark-red and three white) were constructed and analyzed to
      elucidate differences in cyanidin (Cy) metabolism between dark-red and white
      onion bulbs. Libraries were screened using RNA-sequencing (RNA-seq) to reveal the
      differentially expressed genes (DEGs) involved in anthocyanin biosynthesis at the
      transcriptional level. Comparison with the Kyoto Encyclopedia of Genes and
      Genomes (KEGG) database shows that a total of 27 unigenes participate in onion
      anthocyanin biosynthesis and 16 DEGs perform critical roles in flavonoid
      biosynthesis. Expression patterns of color-related flavonoid compounds associated
      with the onion anthocyanin biosynthesis pathway (ABP) show that flavonoid 3',5'
      hydroxylase (F3'5'H) and dihydroflavonol 4-reductase (DFR) genes play crucial
      roles in the biosynthesis of dark-red bulbs, the expression levels of flavonol
      synthase (FLS) and DFR genes may act to block blue pigmentation, and the loss of
      Cy from white onion bulbs might explain multibranching in the synthesis of this
      compound. Positive variation in the F3'5'H/F3'H ratio also affects onion bulb
      color diversity. The transcriptome presented here provides a basis for future
      onion molecular breeding based on variations in the diversity of ornamental plant
      pigmentation.

PMID- 30237462
TI  - Modulation effects of the East Asian winter monsoon on El Nino-related rainfall
      anomalies in southeastern China.
AB  - The present study investigates the modulation of the East Asian winter monsoon
      (EAWM) in the impacts of El Nino on the wintertime rainfall anomalies in
      southeastern China. Here, the variability of the EAWM that is independent of ENSO
      is considered, which is referred to as EAWMres with a strong EAWMres denoting
      anomalous northerly winds. Results demonstrate that strong (weak) EAWMres weakens
      (enhances) the positive rainfall anomalies in southeastern China induced by El
      Nino, because anomalous downward motion over the western North Pacific (WNP)
      associated with El Nino is weakened (strengthened) by strong (weak) EAWMres. The
      modulated convective activity over the WNP, on the one hand, changes the
      anomalous local Hadley circulation associated with El Nino. When El Nino is
      combined with strong (weak) EAWMres, anomalous local Hadley circulation is weak
      (strong) and the resultant anomalous upward motion is weak (strong) over
      southeastern China, leading to small (larger) positive rainfall anomalies there.
      On the other hand, the modulated WNP convective activity induces different low
      level atmospheric responses to El Nino. During an El Nino winter with strong
      (weak) EAWMres, the weak (strong) anomalous suppressed convection produces a weak
      (strong) and insignificant (significant) anomalous low-level WNP anticyclone,
      resulting in correspondingly insignificant (significant) rainfall anomalies in
      southeastern China. Results from a linear baroclinic model further suggest that
      the different low-level atmospheric responses over WNP are mainly induced by
      different diabatic heating associated with El Nino under different EAWMres
      conditions.

PMID- 30237464
TI  - Complex electric double layers in charged topological colloids.
AB  - Charged surfaces in contact with liquids containing ions are accompanied in
      equilibrium by an electric double layer consisting of a layer of electric charge
      on the surface that is screened by a diffuse ion cloud in the bulk fluid. This
      screening cloud determines not only the interactions between charged colloidal
      particles or polyelectrolytes and their self-assembly into ordered structures,
      but it is also pivotal in understanding energy storage devices, such as
      electrochemical cells and supercapacitors. However, little is known to what
      spatial complexity the electric double layers can be designed. Here, we show that
      electric double layers of non-trivial topology and geometry -including tori,
      multi-tori and knots- can be realised in charged topological colloidal particles,
      using numerical modelling within a mean-field Poisson-Boltzmann theory. We show
      that the complexity of double layers -including geometry and topology- can be
      tuned by changing the Debye screening length of the medium, or by changing the
      shape and topology of the (colloidal) particle. More generally, this work is an
      attempt to introduce concepts of topology in the field of charged colloids, which
      could lead to novel exciting material design paradigms.

PMID- 30237465
TI  - Author Correction: Comparison of Image-Guided Intensity-Modulated Radiotherapy
      and Low-dose Rate Brachytherapy with or without External Beam Radiotherapy in
      Patients with Localized Prostate Cancer.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30237466
TI  - Impact of Porphyromonas gingivalis Peptidylarginine Deiminase on Bacterial
      Biofilm Formation, Epithelial Cell Invasion, and Epithelial Cell Transcriptional
      Landscape.
AB  - Peptidylarginine deiminase (PPAD) is a virulence factor unique to pathogenic
      Porphyromonas species, especially P. gingivalis. Mechanistically, PPAD activity,
      in conjunction with Arg-specific gingipains, generates protein fragments with
      citrullinated C-termini. Such polypeptides are potential de novo epitopes that
      are key drivers of rheumatoid arthritis. This process could underlie the observed
      clinical association between rheumatoid arthritis and periodontitis. However, the
      role of PPAD in host colonization by P. gingivalis and, subsequently, in
      triggering periodontitis is not known. Therefore, the aim of the current study
      was to delineate the role of PPAD in bacterial biofilm formation, and to define
      whether adherence to, invasion of, and host responses to bacteria of gingival
      keratinocytes depend on PPAD activity. We studied these aspects using PPAD
      competent and PPAD-incompetent strains of P. gingivalis, and demonstrated that
      neither biofilm formation nor its composition was affected by PPAD activity.
      Similarly, flow cytometry revealed that PPAD did not impact the ability of P.
      gingivalis to adhere to and, subsequently, invade keratinocytes. Network analyses
      of gene expression patterns, however, revealed a group of host genes that were
      sensitive to PPAD activity (CXCL8, IL36G, CCL20, and IL1B). These genes can be
      categorized as potent immune modulators belonging to the interleukin 1 system, or
      chemoattractants of lymphocytes and neutrophils. Thus, we conclude that PPAD,
      although it is a potent modulator of the immune response, does not affect
      bacterial biofilm formation or the ability of P. gingivalis to adhere to and
      invade gingival epithelial cells.

PMID- 30237463
TI  - O-GlcNAcylation on Rab3A attenuates its effects on mitochondrial oxidative
      phosphorylation and metastasis in hepatocellular carcinoma.
AB  - Rab3A is a small Ras-like GTPase critical for membrane traffic. Although the
      functions of Rab3A have been reported in several cancers, the roles of Rab3A in
      hepatocellular carcinoma (HCC) have never been determined. To investigate the
      potential roles of Rab3A in HCC progression, we first determined Rab3A levels in
      HCC tissues and observed upregulated mRNA and protein levels of Rab3A in most
      tumor tissues. However, in vitro data showed that decreasing Rab3A in most HCC
      cell lines conferred no significant effects and overexpressing Rab3A in PLC/PRF/5
      cells even inhibited migration and invasion. Meanwhile, the upregulation of Rab3A
      in HCC patients did not correlate with metastasis or overall survival of HCC
      patients. These contradict data suggested that Rab3A might act as metastatic
      suppressor and its effects might be attenuated in most HCC cells. Further
      experiments revealed that O-GlcNAcylation on Rab3A was key for attenuating Rab3A
      mediated effects by regulating its GTP-binding activity, and verified the effects
      of Rab3A and its aberrant O-GlcNAcylation on HCC metastasis in vitro and in vivo.
      We also found that Rab3A and its O-GlcNAcylation had opposite roles in
      mitochondria oxidative phosphorylation (mtOXPHOS), and their functions on HCC
      metastasis were partially depended on their effects on metabolic reprogramming.

PMID- 30237467
TI  - A randomized clinical trial evaluating choroidal blood flow and morphology after
      conventional and pattern scan laser panretinal photocoagulation.
AB  - We prospectively investigated the changes in choroidal blood flow and morphology
      after panretinal photocoagulation (PRP) in 39 eyes with severe nonproliferative
      diabetic retinopathy (S-NPDR). Seventeen eyes underwent PRP by conventional laser
      and 22 eyes underwent pattern scan laser (PASCAL). The choroidal blood flow was
      assessed by laser speckle flowgraphy, and the subfoveal choroidal thickness
      (SFCT) was measured with optical coherence tomography before and 1, 4, 8, and 12
      weeks after the two types of PRP treatments. The choroidal mean blur rate (MBR)
      at the macular region was significantly reduced to 86.4% of the baseline level in
      the conventional laser group and 85.7% in the PASCAL group at Week 12 (P = 0.001,
      P < 0.001, respectively). The SFCT was significantly increased at 1 week
      following PRP but it was significantly reduced at Week 8 (P = 0.001, P < 0.001,
      respectively) in both groups. The differences in the ratio of the MBR and the
      SFCT was not significant between the conventional laser and PASCAL groups at any
      time after PRP. The results suggest that appropriate PRP treatments even by the
      PASCAL method will reduce the choroidal blood flow and the choroidal
      morphological components.

PMID- 30237454
TI  - Therapeutic approaches to Huntington disease: from the bench to the clinic.
AB  - The 25 years since the identification of the gene responsible for Huntington
      disease (HD) have stood witness to profound discoveries about the nature of the
      disease and its pathogenesis. Despite this progress, however, the development of
      disease-modifying therapies has thus far been slow. Preclinical validation of the
      therapeutic potential of disrupted pathways in HD has led to the advancement of
      pharmacological agents, both novel and repurposed, for clinical evaluation. The
      most promising therapeutic approaches include huntingtin (HTT) lowering and
      modification as well as modulation of neuroinflammation and synaptic
      transmission. With clinical trials for many of these approaches imminent or
      currently ongoing, the coming years are promising not only for HD but also for
      more prevalent neurodegenerative disorders, such as Alzheimer and Parkinson
      disease, in which many of these pathways have been similarly implicated.

PMID- 30237470
TI  - A new era for understanding amyloid structures and disease.
AB  - The aggregation of proteins into amyloid fibrils and their deposition into
      plaques and intracellular inclusions is the hallmark of amyloid disease. The
      accumulation and deposition of amyloid fibrils, collectively known as
      amyloidosis, is associated with many pathological conditions that can be
      associated with ageing, such as Alzheimer disease, Parkinson disease, type II
      diabetes and dialysis-related amyloidosis. However, elucidation of the atomic
      structure of amyloid fibrils formed from their intact protein precursors and how
      fibril formation relates to disease has remained elusive. Recent advances in
      structural biology techniques, including cryo-electron microscopy and solid-state
      NMR spectroscopy, have finally broken this impasse. The first near-atomic
      resolution structures of amyloid fibrils formed in vitro, seeded from plaque
      material and analysed directly ex vivo are now available. The results reveal
      cross-beta structures that are far more intricate than anticipated. Here, we
      describe these structures, highlighting their similarities and differences, and
      the basis for their toxicity. We discuss how amyloid structure may affect the
      ability of fibrils to spread to different sites in the cell and between organisms
      in a prion-like manner, along with their roles in disease. These molecular
      insights will aid in understanding the development and spread of amyloid diseases
      and are inspiring new strategies for therapeutic intervention.

PMID- 30237468
TI  - Prenatal exposure to TiO2 nanoparticles in mice causes behavioral deficits with
      relevance to autism spectrum disorder and beyond.
AB  - Environmental factors are involved in the etiology of autism spectrum disorder
      (ASD) and may contribute to the raise in its incidence rate. It is currently
      unknown whether the increasing use of nanoparticles such as titanium dioxide
      (TiO2 NPs) in consumer products and biomedical applications may play a role in
      these associations. While nano-sized TiO2 is generally regarded as safe and non
      toxic, excessive exposure to TiO2 NPs may be associated with negative health
      consequences especially when occurring during sensitive developmental periods. To
      test if prenatal exposure to TiO2 NPs alters fetal development and behavioral
      functions relevant to ASD, C57Bl6/N dams were subjected to a single intravenous
      injection of a low (100 ug) or high (1000 ug) dose of TiO2 NPs or vehicle
      solution on gestation day 9. ASD-related behavioral functions were assessed in
      the offspring using paradigms that index murine versions of ASD symptoms.
      Maternal exposure to TiO2 NPs led to subtle and dose-dependent impairments in
      neonatal vocal communication and juvenile sociability, as well as a dose
      dependent increase in prepulse inhibition of the acoustic startle reflex of both
      sexes. These behavioral alterations emerged in the absence of pregnancy
      complications. Prenatal exposure to TiO2 NPs did not cause overt fetal
      malformations or changes in pregnancy outcomes, nor did it affect postnatal
      growth of the offspring. Taken together, our study provides a first set of
      preliminary data suggesting that prenatal exposure to nano-sized TiO2 can induce
      behavioral deficits relevant to ASD and related neurodevelopmental disorders
      without inducing major changes in physiological development. If extended further,
      our preclinical findings may provide an incentive for epidemiological studies
      examining the role of prenatal TiO2 NPs exposure in the etiology of ASD and other
      neurodevelopmental disorders.

PMID- 30237469
TI  - A structural investigation of NRZ mediated apoptosis regulation in zebrafish.
AB  - Bcl-2 family proteins play a crucial role in regulating apoptosis, a process
      critical for development, eliminating damaged or infected cells, host-pathogen
      interactions and in disease. Dysregulation of Bcl-2 proteins elicits an expansive
      cell survival mechanism promoting cell migration, invasion and metastasis.
      Through a network of intra-family protein-protein interactions Bcl-2 family
      members regulate the release of cell death factors from mitochondria. NRZ is a
      novel zebrafish pro-survival Bcl-2 orthologue resident on mitochondria and the
      endoplasmic reticulum (ER). However, the mechanism of NRZ apoptosis inhibition
      has not yet been clarified. Here we examined the interactions of NRZ with pro
      apoptotic members of the Bcl-2 family using a combination of isothermal
      calorimetry and mutational analysis of NRZ. We show that NRZ binds almost all
      zebrafish pro-apoptotic proteins and displays a broad range of affinities.
      Furthermore, we define the structural basis for apoptosis inhibition of NRZ by
      solving the crystal structure of both apo-NRZ and a holo form bound to a peptide
      spanning the binding motif of the pro-apoptotic zBad, a BH3-only protein
      orthologous to mammalian Bad. The crystal structure of NRZ revealed that it
      adopts the conserved Bcl-2 like fold observed for other cellular pro-survival Bcl
      2 proteins and employs the canonical ligand binding groove to bind Bad BH3
      peptide. NRZ engagement of Bad BH3 involves the canonical ionic interaction
      between NRZ R86 and Bad D104 and an additional ionic interaction between NRZ D79
      and Bad R100, and substitution of either NRZ R86 or D79 to Ala reduces the
      binding to Bad BH3 tenfold or more. Our findings provide a detailed mechanistic
      understanding for NRZ mediated anti-apoptotic activity in zebrafish by revealing
      binding to both Bad and Noxa, suggesting that NRZ is likely to occupy a unique
      mechanistic role in zebrafish apoptosis regulation by acting as a highly
      promiscuous pro-apoptotic Bcl-2 binder.

PMID- 30237473
TI  - Dystonia.
AB  - Dystonia is a neurological condition characterized by abnormal involuntary
      movements or postures owing to sustained or intermittent muscle contractions.
      Dystonia can be the manifesting neurological sign of many disorders, either in
      isolation (isolated dystonia) or with additional signs (combined dystonia). The
      main focus of this Primer is forms of isolated dystonia of idiopathic or genetic
      aetiology. These disorders differ in manifestations and severity but can affect
      all age groups and lead to substantial disability and impaired quality of life.
      The discovery of genes underlying the mendelian forms of isolated or combined
      dystonia has led to a better understanding of its pathophysiology. In some of the
      most common genetic dystonias, such as those caused by TOR1A, THAP1, GCH1 and
      KMT2B mutations, and idiopathic dystonia, these mechanisms include abnormalities
      in transcriptional regulation, striatal dopaminergic signalling and synaptic
      plasticity and a loss of inhibition at neuronal circuits. The diagnosis of
      dystonia is largely based on clinical signs, and the diagnosis and aetiological
      definition of this disorder remain a challenge. Effective symptomatic treatments
      with pharmacological therapy (anticholinergics), intramuscular botulinum toxin
      injection and deep brain stimulation are available; however, future research will
      hopefully lead to reliable biomarkers, better treatments and cure of this
      disorder.

PMID- 30237472
TI  - C-Abl is not activated in DNA damage-induced and Tap63-mediated oocyte apoptosis
      in human ovary.
AB  - There is a controversy in literature as to whether c-Abl is crucial for the
      induction of TAp63-mediated apoptosis and whether that inhibition of c-Abl with
      imatinib, which was designed to inhibit the oncogenic kinase BCR-ABL and c-kit,
      protects oocytes from chemotherapy-induced apoptosis in mice. No human data are
      available on this issue. We therefore aimed to explore whether genomic damage
      induced by chemotherapy drug cisplatin activates c-Abl along with TAp63 and the
      inhibition of c-Abl with imatinib prevents cisplatin-induced oocyte death and
      follicle loss in human ovary. Exposure to cisplatin induced DNA damage, activated
      TAp63 and SAPK/JNK pathway, and triggered apoptosis in the oocytes and granulosa
      cells. However, TAp63 activation after cisplatin was not associated with any
      increase in the expression of c-Abl. Imatinib did not prevent cisplatin-induced
      apoptosis of the granulosa cells or oocytes. Moreover, treatment with this drug
      resulted in the formation of bizarre shaped follicles lacking oocytes and
      increased follicular atresia by inducing apoptosis of granulosa cells and
      oocytes. Similar toxic effects were observed when ovarian tissue samples were
      incubated with a c-kit antagonist drug anti-CD117, but not with another c-Abl
      tyrosine kinase inhibitor GNF-2, which lacks an inhibitory action on c-kit.
      Intraperitoneal administration of imatinib to the xenografted animals produced
      similar histomorphological abnormalities in the follicles in human ovarian grafts
      and did not prevent cisplatin-induced follicle loss when co-administered with
      cisplatin. Our findings provide, for the first time, a molecular evidence for
      ovarian toxicity of this drug in human. Furthermore, this study together with two
      previous case reports of a severely compromised ovarian response to gonadotropin
      stimulation and premature ovarian failure in patients, while receiving imatinib,
      further heighten the concerns about its potential gonadotoxicity on human ovary
      and urge caution in its use in young female patients.

PMID- 30237471
TI  - Copper-on-nitride enhances the stable electrosynthesis of multi-carbon products
      from CO2.
AB  - Copper-based materials are promising electrocatalysts for CO2 reduction. Prior
      studies show that the mixture of copper (I) and copper (0) at the catalyst
      surface enhances multi-carbon products from CO2 reduction; however, the stable
      presence of copper (I) remains the subject of debate. Here we report a copper on
      copper (I) composite that stabilizes copper (I) during CO2 reduction through the
      use of copper nitride as an underlying copper (I) species. We synthesize a copper
      on-nitride catalyst that exhibits a Faradaic efficiency of 64 +/- 2% for C2+
      products. We achieve a 40-fold enhancement in the ratio of C2+ to the competing
      CH4 compared to the case of pure copper. We further show that the copper-on
      nitride catalyst performs stable CO2 reduction over 30 h. Mechanistic studies
      suggest that the use of copper nitride contributes to reducing the CO
      dimerization energy barrier-a rate-limiting step in CO2 reduction to multi-carbon
      products.

PMID- 30237474
TI  - The impact of chlorhexidine gluconate bathing on skin bacterial burden of
      neonates admitted to the Neonatal Intensive Care Unit.
AB  - OBJECTIVE: To assess the impact of chlorhexidine gluconate (CHG) bathing on skin
      bacterial burden in neonates. STUDY DESIGN: In this prospective observational
      study, arm and groin skin bacterial growth was measured in 40 CHG-exposed and
      nonexposed neonates admitted to the NICU. Exposed neonates received 2% CHG baths
      per protocol for central line-associated bloodstream infection (CLABSI)
      prevention or Staphylococcus aureus decolonization. RESULTS: Forty neonates were
      enrolled, 18 of whom were CHG-exposed. Mean baseline Gram-positive (GP) bacterial
      burden was 2.19 log CFU/ml on the arm and 1.81 log CFU/ml on the groin. Bacterial
      burden decreased after the first bath, but returned to baseline by 72 h. Residual
      skin CHG concentration declined over time, with a corresponding increase in GP
      bacterial burden. CONCLUSIONS: CHG bathing reduces skin bacterial burden, but
      burden returns to baseline after 72 h. Twice weekly CHG bathing may be inadequate
      to suppress skin bacterial growth in hospitalized neonates.

PMID- 30237475
TI  - Survival and healthcare utilization of infants diagnosed with lethal congenital
      malformations.
AB  - OBJECTIVE: We assessed survival, hospital length of stay (LOS), and costs of
      medical care for infants with lethal congenital malformations, and also examined
      the relationship between medical and surgical therapies and survival. STUDY
      DESIGN: Retrospective cohort study including infants born 1998-2009 with lethal
      congenital malformations, identified using a longitudinally linked
      maternal/infant database. RESULTS: The cohort included 786 infants: trisomy 18
      (T18, n = 350), trisomy 13 (T13, n = 206), anencephaly (n = 125), bilateral renal
      agenesis (n = 53), thanatophoric dysplasia/achondrogenesis/lethal osteogenesis
      imperfecta (n = 38), and infants > 1 of the birth defects (n = 14). Compared to
      infants without birth defects, infants with T18, T13, bilateral renal agenesis,
      and skeletal dysplasias had longer survival rates, higher inpatient medical
      costs, and longer LOS. CONCLUSION: Care practices and survival have changed over
      time for infants with T18, T13, bilateral renal agenesis, and skeletal
      dysplasias. This information will be useful for clinicians in counseling families
      and in shaping goals of care prenatally and postnatally.

PMID- 30237476
TI  - Pharmacologic treatment of infants with neonatal abstinence syndrome in community
      hospitals compared to academic medical centers.
AB  - OBJECTIVE: To compare length of hospital stay (LOS), LOS due to neonatal
      abstinence syndrome (NAS), and duration of pharmacologic treatment in community
      or academic settings. STUDY DESIGN: One hundred-two infants exposed to opioids in
      utero at two community hospitals were compared to 256 from eight academic
      centers. All infants were managed with non-pharmacologic care followed by similar
      pharmacologic treatment options. RESULTS: Two hundred-twelve infants received
      pharmacologic treatment for NAS. Mean LOS (24.7 +/- 8.5 vs. 24.5 +/- 11.3 days),
      LOS due to NAS (24.0 +/- 8.2 vs. 23.3 +/- 9.2 days), and duration of NAS
      treatment (19.3 +/- 8.0 vs. 18.9 +/- 9.2 days) were similar in community compared
      to academic medical centers. CONCLUSIONS: No significant differences were found
      in infants managed in the community compared to academic care settings. These
      findings support caring for opioid-exposed infants in both community and academic
      settings with the use of standardized care protocols.

PMID- 30237477
TI  - Consumption of dairy, fruits and dark green leafy vegetables is associated with
      lower risk of adverse pregnancy outcomes (APO): a prospective cohort study in
      rural Ethiopia.
AB  - BACKGROUND: Poor maternal nutrition during pregnancy is a leading modifiable risk
      factor associated with risks of adverse pregnancy outcomes (APO). Nevertheless,
      there is paucity of evidence if consumption of some food groups is associated
      with lower risk of APO, particularly in low-income settings. We aimed to
      determine whether consumption of some food groups is associated with lower risk
      of APOs such as: preterm birth (PTB), low-birth weight (LBW), and stillbirth in
      rural Central Ethiopia. METHODS: A multi-center (8 health centers) prospective
      cohort study, enrolling 432 pregnant women during their initial antenatal care
      visit, was employed. All mothers were then followed monthly (for a total of four
      visits) from enrollment to delivery. Midwives in respective health centers
      assessed dietary diversity using the Women's individual dietary diversity score
      and evaluated birth outcomes following standard procedures. Logistic regression
      models were run to predict association of food groups with the APO. FINDINGS: Out
      of the 374 pregnant women who completed the study, one in five [74 (19.8%)]
      experienced at least one of the APO: 34 (9.1%) gave birth to LBW babies,
      51(13.6%) had PTB and 17 (4.5%) experienced stillbirth. Poor or inconsistent
      consumption (<3/4 assessments) of dark green leafy vegetables (adjusted odds
      ratio (AOR) = 2.01; 95% confidence interval (CI): 1.04-3.87), dairy products (AOR
      = 2.64; 95% CI: 1.11-6.30), and fruits and vegetables (AOR = 2.92; 95% CI: 1.49
      5.67) were independently associated with higher APO risks. Whereas, being
      nonanemic at term (AOR = 0.24; 95% CI: 0.12-0.48) was independently associated
      with lower APO risks. CONCLUSIONS: Poor or inconsistent consumption of dairy,
      dark green leafy vegetables and fruits were associated with higher risk of APOs.
      While community-based trials and mechanistic studies are needed to substantiate
      these findings, efforts to promote dietary diversity through increased
      consumption of fruits, vegetables and dairy may be beneficial in this and similar
      settings.

PMID- 30237479
TI  - Coevolution of teaching ability and cooperation in spatial evolutionary games.
AB  - Individuals with higher reputation are able to spread their social strategies
      easily. At the same time, one's reputation is changing according to his previous
      behaviors, which leads to completely different teaching abilities for players. To
      explore the effect of the teaching ability influenced by reputation, we consider
      a coevolutionary model in which the reputation score affects the updating rule in
      spatial evolutionary games. More precisely, the updating probability becomes
      bigger if his/her partner has a positive reputation. Otherwise, the updating
      probability becomes smaller. This simple design describes the influence of
      teaching ability on strategy adoption effectively. Numerical results focus on the
      proportion of cooperation under different levels of the amplitude of change of
      reputation and the range of reputation. For this dynamics, the fraction of
      cooperators presents a growth trend within a wide range of parameters. In
      addition, to validate the generality of this mechanism, we also employ the
      snowdrift game. Moreover, the evolution of cooperation on Erdos-Renyi random
      graph is studied for the prisoner's dilemma game. Our results may be conducive to
      understanding the emergence and sustainability of cooperation during the strategy
      adoptions in reality.

PMID- 30237478
TI  - Interference with lactate metabolism by mmu-miR-320-3p via negatively regulating
      GLUT3 signaling in mouse Sertoli cells.
AB  - Disruption of the nursery function in Sertoli cells (SCs) by reducing lactate
      production, a preferred energy substrate for developed germ cells (spermatocytes
      and spermatids), is tightly associated with spermatogenic failure such as SC-only
      syndrome (SCOS). However, whether this complicated pathogenesis is regulated by
      certain miRNAs at the post-transcriptional level remain fascinating but largely
      unknown. Here we show for the first time that mmu-miR-320-3p was exclusively
      expressed in murine SCs and this expression was significantly induced in
      busulphan-treated murine testis. The most efficient stimulatory germ cell types
      for the induction of apoptosis-elicited mmu-miR-320-3p expression were meiotic
      spermatocytes and haploid spermatids. Functionally, forced expression of the
      exogenous mmu-miR-320-3p in SCs compromises male fertility by causing
      oligozoospermia and defection of sperm mobility. Mechanistically, mmu-miR-320-3p
      negatively regulates lactate production of SCs by directly inhibiting glucose
      transporter 3 (GLUT3) expression. Thus, dysregulation of mmu-miR-320-3p/GLUT3
      cascade and consequently of lactate deficiency may be a key molecular event
      contributing the germ cell loss by SC dysfunction. Future endeavor in the
      continuous investigation of this important circulating miRNA may shed novel
      insights into epigenetic regulation of SCs nursery function and the etiology of
      azoospermia, and offers novel therapeutic and prognostic targets for SCOS.

PMID- 30237480
TI  - Publisher Correction: Magnetoelectric inversion of domain patterns.
AB  - Four incorrect figure citations in this Letter have been corrected online.

PMID- 30237482
TI  - A Glycomarker for Short-term Prediction of Hepatocellular Carcinoma: A
      Longitudinal Study With Serial Measurements.
AB  - OBJECTIVES: Wisteria floribunda agglutinin-positive human Mac-2-binding protein
      (WFA+-M2BP) is a glycomarker. The present community-based long-term follow-up
      study repeatedly determined the serum WFA+-M2BP level and examined its short- and
      long-term associations with hepatitis C virus (HCV)-related hepatocellular
      carcinoma (HCC). METHODS: A total of 921 participants with antibodies against HCV
      seropositive, but seronegative for hepatitis B surface antigen were enrolled from
      seven townships in Taiwan during 1991-1992. The participants were regularly
      followed and their serum WFA+-M2BP levels were measured at baseline and follow
      up. HCC was ascertained through active follow-up and computerized data linkage
      with the National Cancer Registration System until December 31, 2013. Cox
      proportional hazards and logistic regression models were applied to estimate the
      magnitude of associations between serum WFA+-M2BP levels and HCC. RESULTS: During
      a median follow-up of 21.7 years, 122 new-onset HCC cases were identified.
      Elevated serum WFA+-M2BP levels were associated with an increased risk of HCC (p
      < 0.001). Patients with increasing changes in serum WFA+-M2BP levels, relative to
      their baseline levels, had a 4.36-fold risk of HCC. The areas under receiver
      operating curves (AUROCs) of WFA+-M2BP for predicting HCC showed that the
      prediction efficacy was significantly higher while closer to HCC diagnosis (p =
      0.024). The AUROC was 0.91 for predicting HCC within 1 year by including the
      predictors of age, sex, alanine aminotransferase, alpha-fetoprotein (AFP) and
      WFA+-M2BP. CONCLUSIONS: Serum WFA+-M2BP level may elevate before HCC onset and is
      a short-term predictor of HCC among patients infected with HCV.

PMID- 30237481
TI  - MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and
      cirrhosis.
AB  - Glycine N-methyltransferase (GNMT) is the most abundant methyltransferase in the
      liver and a master regulator of the transmethylation flux. GNMT downregulation
      leads to loss of liver function progressing to fibrosis, cirrhosis, and
      hepatocellular carcinoma. Moreover, GNMT deficiency aggravates cholestasis
      induced fibrogenesis. To date, little is known about the mechanisms underlying
      downregulation of GNMT levels in hepatic fibrosis and cirrhosis. On this basis,
      microRNAs are epigenetic regulatory elements that play important roles in liver
      pathology. In this work, we aim to study the regulation of GNMT by microRNAs
      during liver fibrosis and cirrhosis. Luciferase assay on the 3'UTR-Gnmt was used
      to confirm in silico analysis showing that GNMT is potentially targeted by the
      microRNA miR-873-5p. Correlation between GNMT and miR-873-5p in human cholestasis
      and cirrhosis together with miR-873-5p inhibition in vivo in different mouse
      models of liver cholestasis and fibrosis [bile duct ligation and Mdr2 (Abcb4)-/-
      mouse] were then assessed. The analysis of liver tissue from cirrhotic and
      cholestatic patients, as well as from the animal models, showed that miR-873-5p
      inversely correlated with the expression of GNMT. Importantly, high circulating
      miR-873-5p was also detected in cholestastic and cirrhotic patients. Preclinical
      studies with anti-miR-873-5p treatment in bile duct ligation and Mdr2-/- mice
      recovered GNMT levels in association with ameliorated inflammation and fibrosis
      mainly by counteracting hepatocyte apoptosis and cholangiocyte proliferation. In
      conclusion, miR-873-5p emerges as a novel marker for liver fibrosis, cholestasis,
      and cirrhosis and therapeutic approaches based on anti-miR-873-5p may be
      effective treatments for liver fibrosis and cholestatic liver disease.

PMID- 30237483
TI  - Tooth oxygen isotopes reveal Late Bronze Age origin of Mediterranean fish
      aquaculture and trade.
AB  - Past fish provenance, exploitation and trade patterns were studied by analyzing
      phosphate oxygen isotope compositions (delta18OPO4) of gilthead seabream (Sparus
      aurata) tooth enameloid from archaeological sites across the southern Levant,
      spanning the entire Holocene. We report the earliest evidence for extensive fish
      exploitation from the hypersaline Bardawil lagoon on Egypt's northern Sinai
      coast, as indicated by distinctively high delta18OPO4 values, which became
      abundant in the southern Levant, both along the coast and further inland, at
      least from the Late Bronze Age (3,550-3,200 BP). A period of global, postglacial
      sea-level stabilization triggered the formation of the Bardawil lagoon, which was
      intensively exploited and supported a widespread fish trade. This represents the
      earliest roots of marine proto-aquaculture in Late Holocene coastal domains of
      the Mediterranean. We demonstrate the potential of large-scale delta18OPO4
      analysis of fish teeth to reveal cultural phenomena in antiquity, providing
      unprecedented insights into past trade patterns.

PMID- 30237485
TI  - Comparative study of precise measurements of natural radionuclides and radiation
      dose using in-situ and laboratory gamma-ray spectroscopy techniques.
AB  - In this study, in-situ and laboratory gamma-ray spectroscopy techniques were
      compared to evaluate the activity concentration of natural radionuclides in soil.
      The activity concentrations of 238U (226Ra), 232Th, and 40K in the soil in 11
      sites were simultaneously measured with in-situ portable HPGe and the NaI(Tl)
      detectors. In parallel, 55 soil samples collected from these sites were analyzed
      with a laboratory gamma-ray spectroscopy technique (HPGe). A strong correlation
      was observed between the in-situ and laboratory HPGe techniques with a linear
      correlation coefficient (R2) of 0.99 for 226Ra and 232Th and 0.975 for 40K,
      respectively. The in-situ HPGe technique shows a strong correlation with the
      NaI(Tl) detector. gamma-Rays cps of 226Ra, 232Th, and 40K of the NaI (Tl)
      detector were then converted to specific activities (Bq kg-1 unit) in soil using
      the empirical formulas obtained in this study. The absorbed dose rate in air at 1
      m height above ground due to these radionuclides was calculated using the Beck's
      formula and the results were compared with measured values obtained with an high
      pressure ionization chamber. The results of the calculated and measured dose rate
      show a strong correlation of R2 = 0.96. The reliability and precision of
      analytical spectroscopy techniques of radioactivity and radiation dose were
      confirmed in this work.

PMID- 30237484
TI  - Melatonin attenuates detrimental effects of diabetes on the niche of mouse
      spermatogonial stem cells by maintaining Leydig cells.
AB  - Diabetes mellitus affects a large number of men of reproductive age and it
      usually leads to serious reproductive disorders. However, the underlying
      mechanisms and specific therapies still remain largely unknown. We observed
      Leydig cell loss in the testes of diabetic mice. Continuous high glycemic status
      of testes stimulated expression of Caspase12, Grp78, and Chop, the three ERS
      response factors; this might induce cell cycle arrest and apoptosis of Leydig
      cells in response to ERS. In these diabetic mouse models, melatonin alleviated
      apoptosis of testicular stromal cell induced by ERS, and promoted SSCs self
      renewal by recovering Leydig cells secretion of CSF1 after 8 weeks of treatment.
      To explore the relationship between CSF-1 and ERS in Leydig cells, we treated
      Leydig tumor cell line with an activator Tuniamycin and an inhibitor 4
      Phenylbutyrate of ERS. Our data showed that the CSF-1 expression in mouse Leydig
      cell lines decreased six-fold while reversely increasing five-fold in the 4
      Phenylbutyrate-treated group. Thus, melatonin likely alleviates the loss of
      Leydig cells in diabetic testes and provides a healthier niche for SSCs to self
      renew and continually provide healthy sperm for male fertility.

PMID- 30237486
TI  - Multi-color lasing in chemically open droplet cavities.
AB  - In this paper, we demonstrate FRET-based multicolor lasing within chemically open
      droplet cavities that allow online modulation of the gain medium composition. To
      do this, we generated monodisperse microfluidic droplets loaded with coumarin 102
      (donor), where the spherical droplets acted as whispering gallery mode (WGM)
      optical cavities in which coumarin 102 lasing (~ 470 nm) was observed. The lasing
      color was switched from blue to orange by the introduction of a second dye
      (acceptor, rhodamine 6 G) into the flowing droplet cavities; subsequent lasing
      from rhodamine 6 G (~ 590 nm) was observed together with the complete absence of
      coumarin 102 emission. The ability to control color switching online within the
      same droplet cavity enables sequential detection of multiple target molecules
      within or around the cavity. As a demonstration of this concept, we show how the
      presence of FITC-Dextran and methylene blue (MB) in the medium surrounding the
      lasing droplets can be sequentially detected by the blue and orange laser
      respectively. The method is simple and can be extended to a range of water
      soluble dyes, thus enabling a wide spectral range for the lasing with the use of
      a single pump laser source.

PMID- 30237487
TI  - Recovering Motor Activation with Chronic Peripheral Nerve Computer Interface.
AB  - Interfaces with the peripheral nerve provide the ability to extract motor
      activation and restore sensation to amputee patients. The ability to chronically
      extract motor activations from the peripheral nervous system remains an unsolved
      problem. In this study, chronic recordings with the Flat Interface Nerve
      Electrode (FINE) are employed to recover the activation levels of innervated
      muscles. The FINEs were implanted on the sciatic nerves of canines, and neural
      recordings were obtained as the animal walked on a treadmill. During these
      trials, electromyograms (EMG) from the surrounding hamstring muscles were
      simultaneously recorded and the neural recordings are shown to be free of
      interference or crosstalk from these muscles. Using a novel Bayesian algorithm,
      the signals from individual fascicles were recovered and then compared to the
      corresponding target EMG of the lower limb. High correlation coefficients (0.84
      +/- 0.07 and 0.61 +/- 0.12) between the extracted tibial fascicle/medial
      gastrocnemius and peroneal fascicle/tibialis anterior muscle were obtained.
      Analysis calculating the information transfer rate (ITR) from the muscle to the
      motor predictions yielded approximately 5 and 1 bit per second (bps) for the two
      sources. This method can predict motor signals from neural recordings and could
      be used to drive a prosthesis by interfacing with residual nerves.

PMID- 30237490
TI  - A novel mechanism of plasminogen activation in epithelial and mesenchymal cells.
AB  - Cancer dissemination is initiated by the movement of cells into the vasculature
      which has been reported to be triggered by EMT (epithelial to mesenchymal
      transition). Cellular dissemination also requires proteases that remodel the
      extracellular matrix. The protease, plasmin is a prominent player in matrix
      remodeling and invasion. Despite the contribution of both EMT and the plasminogen
      activation (PA) system to cell dissemination, these processes have never been
      functionally linked. We reveal that canonical Smad-dependent TGFbeta1 signaling
      and FOXC2-mediated PI3K signaling in cells undergoing EMT reciprocally modulate
      plasminogen activation partly by regulating the plasminogen receptor, S100A10 and
      the plasminogen activation inhibitor, PAI-1. Plasminogen activation and
      plasminogen-dependent invasion were more prominent in epithelial-like cells and
      were partly dictated by the expression of S100A10 and PAI-1.

PMID- 30237489
TI  - Meconium microbiome associates with the development of neonatal jaundice.
AB  - OBJECTIVE: Neonatal jaundice is a common disease that affects up to 60% of
      newborns. Gut microbiota mediated the excretion of bilirubin from the human body.
      However, the relationship between early gut microbiome and development of
      neonatal jaundice is not fully understood. Here we sought to characterize
      meconium microbiome of newborns and to clarify its association with risk of
      neonatal jaundice. METHODS: We conducted a nested case-control study with 301
      newborns providing meconium samples from 2014 to 2015. The main outcome was the
      development of neonatal jaundice at 42 day follow-up. 16S rRNA gene sequencing
      was performed to profile the meconium microbiome. LEfSe was employed to identify
      different features between control and case groups. Logistic regression was used
      to estimate the risk effect of early gut microbiome on neonatal jaundice.
      RESULTS: Logistic regression models suggested that higher alpha-diversity was
      significantly associated with lower risk of jaundice in cesarean infants (OR
      0.72, 95% CI 0.52-0.98), but not in infants born naturally. Higher relative
      abundance of Bifidobacterium pseudolongum in newborn meconium was significantly
      associated with lower risk of jaundice both in cesarean-born infants and in the
      total subjects (OR 0.24, 95% CI 0.07-0.68; OR 0.55, 95% CI 0.31-0.95,
      respectively). Spearman's correlations showed that relative abundance of B.
      pseudolongum was significantly correlated with alpha-diversity (P < 0.01).
      CONCLUSION: Preventive and treatment methods implying early gut microbiome
      intervention could be promising for the management of neonatal jaundice.

PMID- 30237491
TI  - Exporting electrons.

PMID- 30237492
TI  - Menisci protect chondrocytes from load-induced injury.
AB  - Menisci in the knee joint are thought to provide stability, increased contact
      area, decreased contact pressures, and offer protection to the underlying
      articular cartilage and bone during joint loading. Meniscal loss or injury is
      typically accompanied by degenerative changes in the knee, leading to an
      increased risk for osteoarthritis in animals including humans. However, the
      detailed mechanisms underlying joint degeneration and the development of
      osteoarthritis remain largely unknown, and the acute effects of meniscal loss
      have not been studied systematically. We developed a microscopy-based system to
      study microscale joint mechanics in living mice loaded by controlled muscular
      contractions. Here, we show how meniscal loss is associated with rapid
      chondrocyte death (necrosis) in articular cartilage within hours of injury, and
      how intact menisci protect chondrocytes in vivo in the presence of intense muscle
      based joint loading and/or injury to the articular cartilage. Our findings
      suggest that loading the knee after meniscal loss is associated with extensive
      cell death in intact and injured knees, and that early treatment interventions
      should be aimed at preventing chondrocyte death.

PMID- 30237494
TI  - Proinsulin-mediated induction of type 1 diabetes in HLA-DR4-transgenic mice.
AB  - Antigen-specific immunotherapy of autoimmune disease currently remains the only
      potentially curative approach. However, translation of promising pre-clinical
      results into successful clinical application has proven challenging. In part,
      this is because pre-clinical findings in mouse models have to be redesigned for
      human application due to differences in MHC II. To reduce the gap between pre
      clinical and clinical studies, we have created a novel mouse model that expresses
      human HLA-DR4, but no endogenous MHC on antigen-presenting cells. Moreover, human
      B7.1 (CD80) is expressed in the pancreatic islets under the control of the rat
      insulin promoter. Although this model does not develop diabetes spontaneously, it
      is susceptible to the induction of type 1 diabetes by challenging mice with
      overlapping peptides derived from murine proinsulin-2 in adjuvant. Unlike the NOD
      model of spontaneous type 1 diabetes, but akin to the human condition, this model
      does not have a gender bias. Furthermore, similar to the human condition, the
      disease is characterised by a diverse leucocyte infiltration of the pancreatic
      islets and the formation of anti-proinsulin auto-antibodies. The model that we
      report here offers detailed insights into type-1 diabetes and is expected to
      prove instrumental when studying the mechanism of action in translational,
      antigen-specific immunotherapy.

PMID- 30237488
TI  - Endogenous metabolites of vitamin E limit inflammation by targeting 5
      lipoxygenase.
AB  - Systemic vitamin E metabolites have been proposed as signaling molecules, but
      their physiological role is unknown. Here we show, by library screening of
      potential human vitamin E metabolites, that long-chain omega-carboxylates are
      potent allosteric inhibitors of 5-lipoxygenase, a key enzyme in the biosynthesis
      of chemoattractant and vasoactive leukotrienes. 13-((2R)-6-hydroxy-2,5,7,8
      tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid (alpha-T-13'-COOH) can
      be synthesized from alpha-tocopherol in a human liver-on-chip, and is detected in
      human and mouse plasma at concentrations (8-49 nM) that inhibit 5-lipoxygenase in
      human leukocytes. alpha-T-13'-COOH accumulates in immune cells and inflamed
      murine exudates, selectively inhibits the biosynthesis of 5-lipoxygenase-derived
      lipid mediators in vitro and in vivo, and efficiently suppresses inflammation and
      bronchial hyper-reactivity in mouse models of peritonitis and asthma. Together,
      our data suggest that the immune regulatory and anti-inflammatory functions of
      alpha-tocopherol depend on its endogenous metabolite alpha-T-13'-COOH,
      potentially through inhibiting 5-lipoxygenase in immune cells.

PMID- 30237493
TI  - LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent
      macrophage recruitment.
AB  - Tumor-associated macrophages (TAMs) are the most abundant inflammatory
      infiltrates in the tumor microenvironment and contribute to lymph node (LN)
      metastasis. However, the precise mechanisms of TAMs-induced LN metastasis remain
      largely unknown. Herein, we identify a long noncoding RNA, termed Lymph Node
      Metastasis Associated Transcript 1 (LNMAT1), which is upregulated in LN-positive
      bladder cancer and associated with LN metastasis and prognosis. Through gain and
      loss of function approaches, we find that LNMAT1 promotes bladder cancer
      associated lymphangiogenesis and lymphatic metastasis. Mechanistically, LNMAT1
      epigenetically activates CCL2 expression by recruiting hnRNPL to CCL2 promoter,
      which leads to increased H3K4 tri-methylation that ensures hnRNPL binding and
      enhances transcription. Furthermore, LNMAT1-induced upregulation of CCL2 recruits
      macrophages into the tumor, which promotes lymphatic metastasis via VEGF-C
      excretion. These findings provide a plausible mechanism for LNMAT1-modulated
      tumor microenvironment in lymphatic metastasis and suggest that LNMAT1 may
      represent a potential therapeutic target for clinical intervention in LN
      metastatic bladder cancer.

PMID- 30237495
TI  - Oncogenic PI3K/AKT promotes the step-wise evolution of combination BRAF/MEK
      inhibitor resistance in melanoma.
AB  - Nearly all patients with BRAF-mutant melanoma will progress on BRAF inhibitor
      monotherapy and combination BRAF/MEK inhibitor therapy within the first year of
      therapy. In the vast majority of progressing melanomas, resistance occurs via the
      re-activation of MAPK signalling, commonly via alterations in BRAF, NRAS and
      MEK1/2. A small proportion of resistant melanomas rely on the activation of the
      compensatory PI3K/AKT signalling cascade, although activation of this pathway
      does not preclude patient responses to BRAF/MEK inhibition. We now show, that
      PI3K/AKT signalling via potent oncogenic PIK3CA and AKT3 mutants, is not
      sufficient to overcome proliferative arrest induced by BRAF/MEK inhibition, but
      rather enables the survival of a dormant population of MAPK-inhibited melanoma
      cells. The evolution of resistance in these surviving tumour cells was associated
      with MAPK re-activation and no longer depended on the initial PI3K/AKT-activating
      oncogene. This dynamic form of resistance alters signalling dependence and may
      lead to the evolution of tumour subclones highly resistant to multiple targeted
      therapies.

PMID- 30237496
TI  - RB1CC1-enhanced autophagy facilitates PSCs activation and pancreatic fibrogenesis
      in chronic pancreatitis.
AB  - Chronic pancreatitis (CP) is described as a progressive fibro-inflammatory
      disorder of the exocrine disease, which eventually leads to damage of the gland.
      Excessive activation of pancreatic stellate cells (PSCs) is a critical
      participant in the initiation of CP. Autophagy is involved in multiple
      degeneration and inflammation in acute pancreatitis and CP. In our study, we
      report that retinoblastoma coiled coil protein 1 (RB1CC1) expression and the
      autophagic level are elevated in activated PSCs. RB1CC1 is positively correlated
      with pancreatic fibrogenesis in tissues and plasma of CP patients. Knockdown of
      RB1CC1 restrains alpha smooth muscle actin (alpha-SMA) and collagen expressions,
      and autophagy in activated PSCs in vitro. Furthermore, we show that RB1CC1
      induces PSC activation via binding to ULK1 promoter and the direct interaction
      with ULK1 protein. These suppress ULK1 expression and its kinase activity. In
      mice, knockdown of RB1CC1 blocks autophagy and then inhibits the pancreatic duct
      ligation-induced pancreatic fibrosis. Consequently, our study highlights that
      RB1CC1-mediated autophagy is a key event for the activation of PSCs. Inhibition
      of RB1CC1 alleviates autophagy, which plays a critical role in anti-fibrotic
      activation in PSCs and CP progression. RB1CC1 could be a novel strategy for the
      treatment of pancreatic fibrosis.

PMID- 30237498
TI  - Continuous positive airway pressure therapy for obstructive sleep apnoea and
      psychotropic drug use: a retrospective observational matched-cohort study.
AB  - Patients with obstructive sleep apnoea (OSA) frequently present symptoms of
      depression, anxiety and insomnia and continuous positive airway pressure (CPAP)
      can improve these symptoms. Using a real-world administrative database, we
      analysed the trend of psychotropic drug use (antidepressants, anxiolytics and
      hypnotics) on a long-term period in OSA individuals before-after CPAP initiation.
      A total of 869 OSA individuals to whom psychotropic drugs were prescribed were
      followed for 4 years. They were matched to 2,607 non-OSA individuals, who were
      similar in terms of demographics, chronic diseases and care consumption.
      Generalized estimating equations models were used to compare psychotropic drug
      defined daily doses (DDD). Results showed no significant differences in mean
      trends of psychotropic drug DDD between OSA individuals and non-OSA matched
      controls during the three years following CPAP initiation. Only time had a
      significant effect on DDD, which decreased in both groups: -9% in Y1 and -17% in
      Y3, compared to Y0 (p-values < 0.0001). Hence, CPAP therapy does not result in an
      earlier decrease of psychotropic drug use in OSA individuals compared to non-OSA
      matched controls. Further studies are needed to analyse long-term psychotropic
      drug use, particularly in non-adherent OSA individuals.

PMID- 30237497
TI  - A miR-125b/CSF1-CX3CL1/tumor-associated macrophage recruitment axis controls
      testicular germ cell tumor growth.
AB  - Tumor growth is modulated by crosstalk between cancer cells and the tumor
      microenvironment. Recent advances have shown that miRNA dysfunction in tumor
      cells can modulate the tumor microenvironment to indirectly determine their
      progression. However, this process is poorly understood in testicular germ cell
      tumors (TGCTs). We reported here that miR-125b was repressed in TGCT samples by
      epigenetic modifications rather than genetic alternations. Furthermore, miR-125b
      overexpression significantly alleviated the tumor growth in two NCCIT human
      embryonic carcinoma xenograft models in vivo, whereas miR-125b did not stimulate
      autonomous tumor cell growth in vitro. Notably, forced expression of miR-125b in
      NCCIT embryonic carcinoma cells decreased the abundance of host tumor-associated
      macrophages (TAMs) within tumor microenvironment. Selective deletion of host
      macrophages by clodronate abolished the anti-tumoral ability of miR-125b in
      xenograft models. By RNA profiling, Western blot and luciferase reporter assay,
      we further observed that miR-125b directly regulated tumor cell-derived chemokine
      CSF1 and CX3CL1, which are known to control the recruitment of TAMs to tumor
      sites. Lastly, we found that one set of miRNAs, which are under the regulation of
      miR-125b, might convergently target CSF1/CX3CL1 in NCCIT cells using miRNA
      profiling. These findings uncover the anticancer effect of miR-125b via mediating
      tumor-stroma crosstalk in xenograft models of TGCTs and raise the possibility of
      targeting miR-125b as miRNA therapeutics.

PMID- 30237501
TI  - Transcriptional profiling of Zygosaccharomyces bailii early response to acetic
      acid or copper stress mediated by ZbHaa1.
AB  - The non-conventional yeast species Zygosaccharomyces bailii is remarkably
      tolerant to acetic acid, a highly important microbial inhibitory compound in Food
      Industry and Biotechnology. ZbHaa1 is the functional homologue of S. cerevisiae
      Haa1 and a bifunctional transcription factor able to modulate Z. bailii adaptive
      response to acetic acid and copper stress. In this study, RNA-Seq was used to
      investigate genomic transcription changes in Z. bailii during early response to
      sublethal concentrations of acetic acid (140 mM, pH 4.0) or copper (0.08 mM) and
      uncover the regulatory network activated by these stresses under ZbHaa1 control.
      Differentially expressed genes in response to acetic acid exposure (297) are
      mainly related with the tricarboxylic acid cycle, protein folding and
      stabilization and modulation of plasma membrane composition and cell wall
      architecture, 17 of which, directly or indirectly, ZbHaa1-dependent. Copper
      stress induced the differential expression of 190 genes mainly involved in the
      response to oxidative stress, 15 ZbHaa1-dependent. This study provides valuable
      mechanistic insights regarding Z. bailii adaptation to acetic acid or copper
      stress, as well as useful information on transcription regulatory networks in pre
      whole genome duplication (WGD) (Z. bailii) and post-WGD (S. cerevisiae) yeast
      species, contributing to the understanding of transcriptional networks' evolution
      in yeasts.

PMID- 30237499
TI  - MicroRNA-3619-5p suppresses bladder carcinoma progression by directly targeting
      beta-catenin and CDK2 and activating p21.
AB  - Current studies indicate that microRNAs (miRNAs) are widely decreased in various
      tumors and function as tumor suppressors by inhibiting cancer cell proliferation,
      survival, invasion, and migration. The potential application of using miRNAs to
      predict therapeutic responses to multiple types of cancer treatment holds high
      promise. In current study, we demonstrate that miR-3619-5p is downregulated in
      bladder cancer (BCa) tissues and cells. Exogenous overexpression of miR-3619-5p
      in BCa cells inhibits proliferation, migration, and invasion. Moreover, a nude
      mouse xenograft model shows that miR-3619-5p inhibits BCa cell growth. We also
      demonstrate that miR-3619-5p leads to the activation of p21 by targeting its
      promoter in BCa cells. Enforced miR-3619-5p expression consistently leads to the
      downregulation of beta-catenin and cyclin-dependent kinase 2 (CDK2) through
      predicted binding sites within the beta-catenin and CDK2 3'-untranslated regions
      (UTRs), respectively. Moreover, beta-catenin and CDK2 knockdown is able to mimic
      BCa cells growth and metastasis effects induced by overexpressing miR-3619-5p. We
      further confirm that miR-3619-5p inhibits Wnt-beta-catenin signal pathway and EMT
      progression in BCa cells. We also found that miR-3619-5p-induced growth arrest
      and metastasis inhibition are p21-dependent in BCa cells. Taken together, these
      results confirm that miR-3619-5p plays a tumor suppressive role in BCa by
      interfering with cell growth and metastasis and may serve as a potential
      therapeutic target in BCa treatment.

PMID- 30237500
TI  - The FAK inhibitor BI 853520 exerts anti-tumor effects in breast cancer.
AB  - Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that regulates a
      plethora of downstream signaling pathways essential for cell migration,
      proliferation and death, processes that are exploited by cancer cells during
      malignant progression. These well-established tumorigenic activities, together
      with its high expression and activity in different cancer types, highlight FAK as
      an attractive target for cancer therapy. We have assessed and characterized the
      therapeutic potential and the biological effects of BI 853520, a novel small
      chemical inhibitor of FAK, in several preclinical mouse models of breast cancer.
      Treatment with BI 853520 elicits a significant reduction in primary tumor growth
      caused by an anti-proliferative activity by BI 853520. In contrast, BI 853520
      exerts effects with varying degrees of robustness on the different stages of the
      metastatic cascade. Together, the data demonstrate that the repression of FAK
      activity by the specific FAK inhibitor BI 853520 offers a promising anti
      proliferative approach for cancer therapy.

PMID- 30237503
TI  - Cu-bearing stainless steel reduces cytotoxicity and crystals adhesion after
      ureteral epithelial cells exposing to calcium oxalate monohydrate.
AB  - Calcium oxalate monohydrate (COM), which is the main component of encrustation,
      may result in cell membrane injury. In addition, cellular damage is suggested to
      be the primary event attributing to COM crystal binding. To study the interaction
      between cells and crystals after incubating with a Cu-bearing stainless steel
      (316L-Cu SS), MTS and flow cytometric analyses were used to assess the cellular
      responses. The results confirmed that 316L-Cu SS could inhibit cytotoxicity and
      cellular apoptosis of ureteral epithelial cells (UECs) after COM treatment.
      Furthermore, molecular expressions of Cu/Zn superoxide dismutase (CuZnSOD), which
      were evaluated by western blot analysis and real-time quantitative PCR (qPCR),
      indicated that 316L-Cu SS could inhibit the oxidative stress attributing to up
      regulating of CuZnSOD. Moreover, the crystal adhesion cytokine CD44 was examined
      with western blot and qPCR, and the corresponding hyaluronic (HA) secreted into
      the medium was measured by enzyme-linked immunosorbent assay (ELISA). All results
      were confirmed that the expressions of cells cultured with 316L-Cu SS were down
      regulated, demonstrating the inhibitory performance of 316L-Cu SS against crystal
      adhesion.

PMID- 30237502
TI  - Author Correction: Commensal microflora-induced T cell responses mediate
      progressive neurodegeneration in glaucoma.
AB  - The originally published version of this Article contained an error in Figure 4.
      The bar chart in panel f was inadvertently replaced with a duplicate of the bar
      chart in panel e. This error has now corrected in both the PDF and HTML versions
      of the Article.

PMID- 30237504
TI  - IGF1R upregulation confers resistance to isoform-specific inhibitors of PI3K in
      PIK3CA-driven ovarian cancer.
AB  - Genomic alterations (GA) in PIK3CA leads to the hyper-activation of the
      phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K) pathway in more than 20%
      of ovarian cancer (OC) patients. Therefore, PI3K therapies are under clinical
      evaluation for this subset of patients. Evidently, in clinical trials testing the
      efficacy of isoform-specific inhibitors of PI3K (PI3Ki), patients having a stable
      disease eventually relapse, as tumors become resistant to treatment. Hence, there
      is an urgent clinical need to develop new therapeutic combinations to improve the
      efficacy of PI3Ki in PIK3CA-driven OC patients. Here we identified the molecular
      mechanism that limits the efficacy of the beta-sparing PI3Ki, Taselisib
      (GDC0032), in PIK3CA-mutated OC cell lines (IGROV1 and OAW42) that acquired
      resistance to GDC0032. By comparing the molecular profile of GDC0032-sensitve and
      -resistant OC cell lines, we found that AKT/mTOR inhibition is required for
      GDC0032 efficacy. In resistant cells, the sustained activation of AKT/mTOR was
      regulated by the upregulation of the insulin growth factor 1 receptor (IGF1R).
      Knockdown of IGF1R re-sensitized cells to GDC0032 in vitro, and the combination
      of AEW541, an IGF1R inhibitor, with GDC0032 exhibited potent anti-tumor activity
      in vitro and in vivo. We further demonstrated that IGF1R regulates tumor cell
      proliferation in IGROV1 cells, whereas in OAW42, it determines autophagy as well.
      Overall, our findings suggest that the dual inhibition of PI3K and IGF1R may be
      considered as a new therapeutic strategy in PIK3CA-driven OC.

PMID- 30237506
TI  - Nitrite producing bacteria inhibit reinforcement bar corrosion in cementitious
      materials.
AB  - Chemicals and synthetic coatings are widely used to protect steel against
      corrosion. Bio-based corrosion inhibition strategies can be an alternative in the
      arising bioeconomy era. To maintain the good state of steel reinforcement in
      cracked concrete, microbe-based self-healing cementitious composites (MSCC) have
      been developed. Yet, proposed strategies involve reasonably slow crack filling by
      biomineralization and thus risk the possible rebar corrosion during crack
      healing. Here we upgrade the rebar protection to a higher level by combining MSCC
      with microbial induced corrosion inhibition. Presented NO3- reducing bacterial
      granules inhibit rebar corrosion by producing the anodic corrosion inhibitor NO2-
      and meanwhile heal a 300-um-wide crack in 28 days. During 120 days exposure to
      0.5 M Cl- solution, the rebars in cracked MSCC keep showing open circuit
      potentials above the critical value of -250 mV and they lose less than 2% of the
      total rebar material which corresponds to half the material loss in cracked plain
      mortar. Overall, the obtained rebar protection performance is comparable with
      that of uncracked mortar and mortar containing chemical inhibitor, hence the
      microbe-based system becomes an alternative to the traditional methods.

PMID- 30237505
TI  - Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind
      randomized-controlled trial.
AB  - OBJECTIVES: Patients with type 2 diabetes (T2DM) are at increased fracture risk.
      Resveratrol has shown beneficial effects on bone health in few studies. The aim
      of this trial was to investigate the effects of resveratrol on bone mineral
      density (BMD) and on calcium metabolism biomarkers in T2DM patients. METHODS: In
      this double-blind randomized placebo-controlled trial 192 T2DM outpatients were
      randomized to receive resveratrol 500 mg/day (Resv500 arm), resveratrol 40 mg/day
      (Resv40 arm) or placebo for 6 months. BMD, bone mineral content (BMC), serum
      calcium, phosphorus, alkaline phosphatase, and 25-hydroxy vitamin D were measured
      at baseline and after 6 months. RESULTS: At follow-up, calcium concentrations
      increased in all patients, while within-group variations in alkaline phosphatase
      were higher in both resveratrol arms, and 25-hydroxy vitamin D increased in the
      Resv500 arm only, without between-group differences. Whole-body BMD significantly
      decreased in the placebo group, while whole-body BMC decreased in both the
      placebo and Resv40 arms. No significant changes in BMD and BMC values occurred in
      the Resv500 arm. The adjusted mean differences of change from baseline were
      significantly different in the Resv500 arm vs placebo for whole-body BMD (0.01 vs
      -0.03 g/cm2, p = 0.001), whole-body BMC (4.04 vs -58.8 g, p < 0.001), whole-body
      T-score (0.15 vs -0.26), and serum phosphorus (0.07 vs -0.01 umol/L, p = 0.002).
      In subgroup analyses, in Resv500 treated-patients BMD values increased to higher
      levels in those with lower calcium and 25-hydroxy vitamin D values, and in
      alcohol drinkers. CONCLUSIONS: Supplementation with 500 mg resveratrol prevented
      bone density loss in patients with T2DM, in particular, in those with unfavorable
      conditions at baseline.

PMID- 30237507
TI  - Author Correction: The acoustic phase resonances and surface waves supported by a
      compound rigid grating.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30237508
TI  - The synergic effects of frailty on disability associated with urbanization,
      multimorbidity, and mental health: implications for public health and medical
      care.
AB  - Frailty is garnering increasing interest as a potential target in disability
      prevention. Since it is uncertain how frailty interacts with multimorbidity,
      urbanization, and mental health to affect disability, we investigated the
      epidemiology of frailty and its synergies with these factors. The study enrolled
      20,898 participants aged 65 and older living in New Taipei city. All participants
      received face to face interview to assess frailty, multimorbidity, urban or rural
      residence, and mental health. Individual versus combined effects of risk factors
      were evaluated using the Rothman synergy index. Prevalence of frailty was 5.2%
      overall, 7.2% in multimorbid participants, 9.6% in rural residents, and 20.8% in
      those with mental disorders. Logistic regression, adjusted for age and sex,
      showed significant associations between disability and frailty (OR 8.5, 95% CI
      6.4-11.2), multimorbidity (OR 1.3, 95% CI 1.0-1.6), urbanization (OR 1.3, 95% CI
      1.0-1.7), and mental disorders (OR 7.3, 95% CI 5.6-9.5); these factors had a
      significant synergic effect on disability. Frailty is common in older adults and
      associated with disability, and was synergetic with multimorbidity, mental
      disorders, and residing rurally. Targeting frailty prevention and intervention
      needs a special attention on those vulnerable groups.

PMID- 30237509
TI  - Systematic genetic mapping of necroptosis identifies SLC39A7 as modulator of
      death receptor trafficking.
AB  - Regulation of cell and tissue homeostasis by programmed cell death is a
      fundamental process with wide physiological and pathological implications. The
      advent of scalable somatic cell genetic technologies creates the opportunity to
      functionally map such essential pathways, thereby identifying potential disease
      relevant components. We investigated the genetic basis underlying necroptotic
      cell death by performing a complementary set of loss-of-function and gain-of
      function genetic screens. To this end, we established FADD-deficient haploid
      human KBM7 cells, which specifically and efficiently undergo necroptosis after a
      single treatment with either TNFalpha or the SMAC mimetic compound birinapant. A
      series of unbiased gene-trap screens identified key signaling mediators, such as
      TNFR1, RIPK1, RIPK3, and MLKL. Among the novel components, we focused on the zinc
      transporter SLC39A7, whose knock-out led to necroptosis resistance by affecting
      TNF receptor surface levels. Orthogonal, solute carrier (SLC)-focused CRISPR/Cas9
      based genetic screens revealed the exquisite specificity of SLC39A7, among ~400
      SLC genes, for TNFR1-mediated and FAS-mediated but not TRAIL-R1-mediated
      responses. Mechanistically, we demonstrate that loss of SLC39A7 resulted in
      augmented ER stress and impaired receptor trafficking, thereby globally affecting
      downstream signaling. The newly established cellular model also allowed genome
      wide gain-of-function screening for genes conferring resistance to necroptosis
      via the CRISPR/Cas9-based synergistic activation mediator approach. Among these,
      we found cIAP1 and cIAP2, and characterized the role of TNIP1, which prevented
      pathway activation in a ubiquitin-binding dependent manner. Altogether, the gain
      of-function and loss-of-function screens described here provide a global genetic
      chart of the molecular factors involved in necroptosis and death receptor
      signaling, prompting further investigation of their individual contribution and
      potential role in pathological conditions.

PMID- 30237510
TI  - PP4 deficiency leads to DNA replication stress that impairs immunoglobulin class
      switch efficiency.
AB  - The serine/threonine phosphatase PP4 has been implicated in DNA damage repair and
      cell cycle regulation through its dephosphorylation of specific substrates. We
      previously showed that PP4 is required for mouse B cell development, germinal
      center (GC) formation and immunoglobulin (Ig) class switch recombination (CSR).
      Here, we investigate the mechanisms underlying this requirement and demonstrate
      that murine PP4-deficient B lymphocytes have a defect in cell proliferation.
      Strikingly, the DNA damage response pathway that involves ATM/p53 and is linked
      to cell cycle arrest and impaired cell survival is strongly induced in these
      mutant B cells. In response to LPS + IL-4, stimuli that trigger IgG1 production,
      these PP4-deficient B cells show inefficient phosphorylation of ATR, leading to
      reduced retention of gammaH2AX-NBS1 complexes at sites of DNA damage, and
      compromised switching to IgG1. However, beyond the cell proliferation phase,
      conditional deletion of PP4 under the control of AID/cre completely restores
      normal IgG1 production in mutant B cell cultures. In vivo, co-deletion of PP4 and
      p53 by AID/cre partially rescues switching to IgG1 in B cells of mice immunized
      with TNP-KLH. Our findings establish that PP4 is indispensable for preventing DNA
      replication stress that could interfere with CSR, thereby promoting antibody
      switching during the humoral immune response.

PMID- 30237511
TI  - SPOP suppresses prostate cancer through regulation of CYCLIN E1 stability.
AB  - SPOP is one of the important subunits for CUL3/SPOP/RBX1 complex tightly
      connected with tumorigenesis. However, its exact roles in different cancers
      remain debatable. Here, we identify CYCLIN E1, as a novel substrate for SPOP.
      SPOP directly interacts with CYCLIN E1 and specific regulates its stability in
      prostate cancer cell lines. SPOP/CUL3/RBX1 complex regulates CYCLIN E1 stability
      through poly-ubiquitination. CDK2 competes with SPOP for CYCLIN E1 interaction,
      suggesting that SPOP probably regulates the stability of CDK2-free CYCLIN E1.
      CYCLIN E1 expression rescued proliferation, migration, and tumor formation of
      prostate cancer cell suppressed by SPOP. Furthermore, we found SPOP selectively
      regulates the substrates' stability and signaling pathways in prostate cancer and
      CCRC cell lines, suggesting that complicated mechanisms exist for SPOP to
      regulate substrate specificity. Altogether, we have revealed a novel mechanism
      for SPOP in suppressing prostate cancer and provided evidence to show SPOP has
      dual functions in prostate cancer and CCRC.

PMID- 30237512
TI  - RIF1 promotes tumor growth and cancer stem cell-like traits in NSCLC by protein
      phosphatase 1-mediated activation of Wnt/beta-catenin signaling.
AB  - Wnt/beta-catenin signaling is essential for proliferation and maintenance of
      cancer stem cell-like traits of various cancer cells. In non-small-cell lung
      carcinoma (NSCLC), the mechanisms underlying the hyperactivation of Wnt signaling
      remain unclear, as mutations in APC and beta-catenin genes are rare in NSCLC.
      RIF1 has been shown upregulated in breast and cervical cancer, this study intends
      to find out the potential effects of the expression and biological functions of
      RIF1 in NSCLC. Here we revealed that RIF1 was highly expressed in NCSLC at both
      mRNA and protein levels. RIF1 expression was significantly associated with
      clinical stage (P < 0.05) and prognosis (P < 0.001) of NSCLC patients. RIF1
      knockdown inhibited NSCLC cell growth in vitro and in vivo, whereas
      overexpression of RIF1 in NSCLC cell lines promoted cell growth, cell cycle
      progression and cancer stem cell (CSC)-like properties via promoting PP1-AXIN
      interaction and thereby activating Wnt/beta-catenin signaling. Inhibition of PP1
      in RIF1-overexpressed cells counteracted the effects of RIF1 on cell growth and
      CSC-like phenotype, as well as the Wnt/beta-catenin signaling. RIF1 expression
      was positively correlated with beta-catenin at the protein level in 32 NSCLC
      tissues. RIF1 expression closely related to MYC (r = 0.28, P < 0.001) and CCND1
      (r = 0.14, P < 0.01) expression at the mRNA level in cohorts of The Cancer Genome
      Atlas (TCGA). These results indicated that RIF1 had an oncogenic role as a novel
      positive regulator of Wnt/beta-catenin signaling by directing PP1 to
      dephosphorylate AXIN; this novel mechanism may present a new therapeutic target
      for NSCLC.

PMID- 30237513
TI  - Pharmacological Characterization of Dezocine, a Potent Analgesic Acting as a
      kappa Partial Agonist and MU Partial Agonist.
AB  - Dezocine is becoming dominated in China market for relieving moderate to severe
      pain. It is believed that Dezocine's clinical efficacy and little chance to
      provoke adverse events during the therapeutic process are mainly attributed to
      its partial agonist activity at the MU opioid receptor. In the present work, we
      comprehensively studied the pharmacological characterization of Dezocine and
      identified that the analgesic effect of Dezocine was a result of action at both
      the kappa and MU opioid receptors. We firstly found that Dezocine displayed
      preferential binding to MU opioid receptor over kappa and delta opioid receptors.
      Dezocine, on its own, weakly stimulated G protein activation in cells expressing
      kappa and MU receptors, but in the presence of full kappa agonist U50,488 H and
      MU agonist DAMGO, Dezocine inhibited U50,488H- and DAMGO-mediated G protein
      activation, indicating that Dezocine was a kappa partial agonist and MU partial
      agonist. Then the in intro results were verified by in vivo studies in mice. We
      observed that Dezocine-produced antinociception was significantly inhibited by
      kappa antagonist nor-BNI and MU antagonist beta-FNA pretreatment, indicating that
      Dezocine-mediated antinociception was via both the kappa and MU opioid receptors.
      When co-administrating of Dezocine with U50,488 H or morphine, Dezocine was
      capable of inhibiting U50,488H- or morphine-induced antinociception. Finally,
      kappa receptor activation-associated side effect sedation was investigated. We
      found that Dezocine displayed limited sedative effect with a ceiling effecting at
      a moderate dose. Thus, our work led to a better understanding of the analgesic
      mechanism of action of Dezocine in vivo.

PMID- 30237515
TI  - Rapid migration of CO2-rich micro-fluids in calcite matrices.
AB  - The transport of supercritical fluids is a determining factor for several
      geological processes and fundamental in predicting natural resource accumulation
      and distribution. Calcite, ubiquitous in most geological environments, may
      contain supercritical CO2 trapped under the form of fluid inclusions that may
      move through grain boundaries affecting the rock physical properties. However,
      despite macroscopic evidence for this process, until recent it was not possible
      to characterize this process at the nano-scale due to the difficulty of such
      observations. In this study, we report nanometer-scale observations on calcite
      crystal surfaces and demonstrate that stress with absence of visible deformation
      produces fluid leakage from fluid inclusions. Atomic Force Microscopy scanning
      experiments on freshly cleaved calcite crystals containing visible fluid
      inclusions revealed the spontaneous formation of nanometer-scale hillocks on flat
      crystal terraces in only a few minutes, without evidence of surface dissolution.
      The fact the hillocks formed on flat surface in a short time was unexpected and
      suggests deposition of material from the inner crystal to the surface through
      small-scale fluid migration. We estimated the rate of this fluid mobility is by
      several orders of magnitude higher than the diffusion rate through vacancies
      estimated in calcite crystals showing that CO2-rich fluids through micro-pore and
      nano-pore spaces is in reality much higher than previously assumed using current
      predictive models.

PMID- 30237516
TI  - Hepatitis B.

PMID- 30237514
TI  - Polybrene induces neural degeneration by bidirectional Ca2+ influx-dependent
      mitochondrial and ER-mitochondrial dynamics.
AB  - Hexadimethrine bromide (Polybrene) was once used clinically as a heparin
      neutralizer and has recently found use as a promoter in virus-mediated gene
      therapy trials and gene transfer in research. However, the potential for tissue
      specific toxicity of polybrene at low doses has been ignored so far. Here, we
      found that after intracerebroventricular (ICV) polybrene injection, mice showed
      disability of movement accompanied neural death and gliosis in brain, and in
      human neurons, polybrene induces concentration-dependent neuritic beading and
      fragmentation. Mechanistically, polybrene induces a rapid voltage-dependent
      calcium channel (VDCC)-mediated influx of extracellular Ca2+. The elevated
      cytoplasmic Ca2+ activates DRP1, which leads to mitochondrial fragmentation and
      metabolic dysfunction. At the same time, Ca2+ influx induces endoplasmic
      reticulum (ER) fragmentation and tightened associations between ER and
      mitochondria, which makes mitochondria prone to Ca2+ overloading and ensuing
      permeability transition. These results reveal an unexpected neuronal toxicity of
      polybrene, wherein Ca2+ influx serves as a regulator for both mitochondrial
      dynamics and ER-mitochondrial remodeling.

PMID- 30237517
TI  - High-entropy alloy strengthened by in situ formation of entropy-stabilized nano
      dispersoids.
AB  - A significant increase in compressive yield strength of the Al0.3CoCrFeMnNi high
      entropy alloy (HEA) from 979 MPa to 1759 MPa was observed upon the introduction
      of 3 vol.% Y2O3. The HEAs were processed using spark plasma sintering of
      mechanically alloyed powders. Transmission electron microscopy and atom probe
      tomography confirmed the presence of compositionally complex nano-dispersoids in
      the Y2O3-added HEA. The significant increase in strength can be attributed to the
      nano-dispersoid strengthening coupled with grain refinement. Therefore, the in
      situ formation of the compositionally complex nanoscale dispersoids during the
      alloy processing could be a novel approach to create entropy-stabilized oxide
      particles in strengthening of HEAs.

PMID- 30237519
TI  - Chemoprevention of Barrett's oesophagus: a step closer with PPIs and aspirin.

PMID- 30237520
TI  - Cellular Depletion of BRD8 Causes p53-Dependent Apoptosis and Induces a DNA
      Damage Response in Non-Stressed Cells.
AB  - Regulation of the chromatin state is crucial for biological processes such as the
      regulation of transcription, DNA replication, and DNA damage repair. Here we show
      that knockdown of the BRD8 bromodomain protein - a subunit of the p400/Tip60
      complex - leads to p21 induction, and concomitant cell cycle arrest in G1/S. We
      further demonstrate that the p53 transcriptional pathway is activated in BRD8
      depleted cells, and this accounts for upregulation of not only p21 but also of
      pro-apoptotic genes, leading to subsequent apoptosis. Importantly, the DNA damage
      response (DDR) is induced upon BRD8 depletion, and DNA damage foci are detectable
      in BRD8-depleted cells under normal growth conditions. Consistently with an
      activated DDR, we find that in BRD8-depleted cells, the ATM-CHK2 DDR pathway is
      turned on but, CHK1 proteins levels are severely reduced and replication stress
      is detectable as enhanced replication protein A (RPA32) phosphorylation levels.
      Notably, acetylation of histone H4 at K16 (H4K16ac) is reduced in BRD8-depleted
      cells, suggesting that BRD8 may have a role in the recruitment and/or
      stabilization of the p400/Tip60 complex within chromatin, thereby facilitating
      DNA repair. Taken together, our results suggest that BRD8 is involved not only in
      p53-dependent gene suppression, but also in the maintenance of genome stability.

PMID- 30237518
TI  - Structural basis for recognition of the malaria vaccine candidate Pfs48/45 by a
      transmission blocking antibody.
AB  - The quest to develop an effective malaria vaccine remains a major priority in the
      fight against global infectious disease. An approach with great potential is a
      transmission-blocking vaccine which induces antibodies that prevent establishment
      of a productive infection in mosquitos that feed on infected humans, thereby
      stopping the transmission cycle. One of the most promising targets for such a
      vaccine is the gamete surface protein, Pfs48/45. Here we establish a system for
      production of full-length Pfs48/45 and use this to raise a panel of monoclonal
      antibodies. We map the binding regions of these antibodies on Pfs48/45 and
      correlate the location of their epitopes with their transmission-blocking
      activity. Finally, we present the structure of the C-terminal domain of Pfs48/45
      bound to the most potent transmission-blocking antibody, and provide key
      molecular information for future structure-guided immunogen design.

PMID- 30237521
TI  - Engineering of entanglement and spin state transfer via quantum chains of atomic
      spins at large separations.
AB  - Several recent experiments have shown that long-range exchange interactions can
      determine collective magnetic ground states of nanostructures in bulk and on
      surfaces. The ability to generate and control entanglement in a system with long
      range interaction will be of great importance for future quantum technology. An
      important step forward to reach this goal is the creation of entangled states for
      spins of distant magnetic atoms. Herein, the generation of long-distance
      entanglement between remote spins at large separations in bulk and on surface is
      studied theoretically, based on a quantum spin Hamiltonian and time-dependent
      Schrodinger equation for experimentally realized conditions. We demonstrate that
      long-distance entanglement can be generated between remote spins by using an
      appropriate quantum spin chain (a quantum mediator), composed by sets of
      antiferromagnetically coupled spin dimers. Ground state properties and quantum
      spin dynamics of entangled atoms are studied. We demonstrate that one can
      increase or suppress entanglement by adding a single spin in the mediator. The
      obtained result is explained by monogamy property of entanglement distribution
      inside a quantum spin system. We present a novel approach for non-local sensing
      of remote magnetic adatoms via spin entanglement.

PMID- 30237522
TI  - Intentional polarity conversion of AlN epitaxial layers by oxygen.
AB  - Nitride materials (AlN, GaN, InN and their alloys) are commonly used in
      optoelectronics, high-power and high-frequency electronics. Polarity is the
      essential characteristic of these materials: when grown along c-direction, the
      films may exhibit either N- or metal-polar surface, which strongly influences
      their physical properties. The possibility to manipulate the polarity during
      growth allows to establish unique polarity in nitride thin films and nanowires
      for existing applications but also opens up new opportunities for device
      applications, e.g., in non-linear optics. In this work, we show that the polarity
      of an AlN film can intentionally be inverted by applying an oxygen plasma. We
      anneal an initially mixed-polar AlN film, grown on sapphire substrate by metal
      organic vapor phase epitaxy (MOVPE), with an oxygen plasma in a molecular beam
      epitaxy (MBE) chamber; then, back in MOVPE, we deposit a 200 nm thick AlN film on
      top of the oxygen-treated surface. Analysis by high-resolution probe-corrected
      scanning transmission electron microscopy (STEM) imaging and electron energy-loss
      spectroscopy (EELS) evidences a switch of the N-polar domains to metal polarity.
      The polarity inversion is mediated through the formation of a thin AlxOyNz layer
      on the surface of the initial mixed polar film, induced by the oxygen annealing.

PMID- 30237523
TI  - Vps34/PI3KC3 deletion in kidney proximal tubules impairs apical trafficking and
      blocks autophagic flux, causing a Fanconi-like syndrome and renal insufficiency.
AB  - Kidney proximal tubular cells (PTCs) are highly specialized for ultrafiltrate
      reabsorption and serve as paradigm of apical epithelial differentiation.
      Vps34/PI3-kinase type III (PI3KC3) regulates endosomal dynamics, macroautophagy
      and lysosomal function. However, its in vivo role in PTCs has not been evaluated.
      Conditional deletion of Vps34/PI3KC3 in PTCs by Pax8-Cre resulted in early (P7)
      PTC dysfunction, manifested by Fanconi-like syndrome, followed by kidney failure
      (P14) and death. By confocal microscopy, Vps34?/? PTCs showed preserved apico
      basal specification (brush border, NHERF-1 versus Na+/K+-ATPase, ankyrin-G) but
      basal redistribution of late-endosomes/lysosomes (LAMP-1) and mis-localization to
      lysosomes of apical recycling endocytic receptors (megalin, cubilin) and apical
      non-recycling solute carriers (NaPi-IIa, SGLT-2). Defective endocytosis was
      confirmed by Texas-red-ovalbumin tracing and reduced albumin content. Disruption
      of Rab-11 and perinuclear galectin-3 compartments suggested mechanistic clues for
      defective receptor recycling and apical biosynthetic trafficking. p62-dependent
      autophagy was triggered yet abortive (p62 co-localization with LC3 but not LAMP
      1) and PTCs became vacuolated. Impaired lysosomal positioning and blocked
      autophagy are known causes of cell stress. Thus, early trafficking defects show
      that Vps34 is a key in vivo component of molecular machineries governing apical
      vesicular trafficking, thus absorptive function in PTCs. Functional defects
      underline the essential role of Vps34 for PTC homeostasis and kidney survival.

PMID- 30237524
TI  - Analysis of miRNAs and their target genes in five Melilotus albus NILs with
      different coumarin content.
AB  - MicroRNAs (miRNAs) exhibit diverse and important roles in regulation of various
      biological processes at the post-transcriptional level in plants. In this study,
      Melilotus albus miRNA and their target genes were elucidated from five M. albus
      near-isogenic lines which differ in coumarin content to construct small RNA
      libraries through high-throughput sequencing. A total of 417 known miRNAs and 76
      novel miRNAs were identified in M. albus. In addition, 4155 different target
      genes for 114 known miRNA families and 14 target genes for 2 novel miRNAs were
      identified in M. albus. Moreover, mtr-miR5248 and mtr-miR7701-5p target c35498_g3
      and gma-miR396a-3p target c37211_g1 involved in coumarin biosynthesis were
      identified by using the differential expression of the miRNAs and their target
      genes correlation analysis. The abundance of miRNAs and potential target genes
      were validated by qRT-PCR analysis. We also found that there were both positive
      and negative expression changing patterns between miRNAs and their related target
      genes. Our first and preliminary study of miRNAs will contribute to our
      understanding of the functions and molecular regulatory mechanisms of miRNAs and
      their target genes, and provide information on regulating the complex coumarin
      pathway in M. albus for future research.

PMID- 30237525
TI  - Identification of high-risk human papillomavirus and Rb/E2F pathway genomic
      alterations in mutually exclusive subsets of colorectal neuroendocrine carcinoma.
AB  - Colorectal neuroendocrine carcinomas, both small cell and large cell types, are
      highly aggressive tumors with poor prognosis compared with colorectal
      adenocarcinoma. The molecular drivers of neuroendocrine carcinoma are best
      defined in small cell lung cancer, which shows near-universal genomic alterations
      in TP53 and RB1. The genetics of colorectal neuroendocrine carcinoma remain
      poorly understood; recent studies demonstrated infrequent RB1 alterations and
      genetics closely resembling colorectal adenocarcinoma. To better define the
      molecular pathogenesis of colorectal neuroendocrine carcinoma, we performed
      capture-based next-generation sequencing on 25 cases and evaluated for expression
      of p53, Rb, p16, and high-risk human papillomavirus (HR-HPV) subtypes using
      immunohistochemistry, in situ hybridization, and polymerase chain reaction.
      Rb/E2F pathway dysregulation was identified in nearly all cases (23/25, 92%) and
      occurred via three distinct mechanisms. First, RB1 genomic alteration was present
      in 56% (14/25) of cases and was accompanied by Rb protein loss, high p16
      expression, and absence of HR-HPV; these cases also had frequent genomic
      alterations in TP53, the PI3K/Ras and Wnt pathways, as well as in DNA repair
      genes, with 4/14 cases being hypermutated. Second, 16% (4/25) of cases, all left
      sided, had TP53 alteration without RB1 alteration; half of these harbored high
      level amplifications in CCNE1 and MYC or MYCN and arose in patients with
      ulcerative colitis. Finally, 28% (7/25) of cases, all rectal or anal, lacked
      genomic alterations in RB1 or TP53 but were positive for HR-HPV. Our data
      demonstrate that Rb/E2F pathway dysregulation is essential in the pathogenesis of
      colorectal neuroendocrine carcinoma, akin to neuroendocrine carcinomas in other
      anatomic sites. Moreover, colorectal neuroendocrine carcinomas stratify into
      three distinct molecular subgroups, which can be differentiated based on Rb
      protein and HR-HPV status. HR-HPV infection represents a distinct mechanism for
      Rb and p53 inactivation in cases lacking genomic alterations in either gene.
      Differential treatment strategies for hypermutated and HPV-driven cases could
      improve patient outcomes.

PMID- 30237526
TI  - IFITM1 expression is crucial to gammaherpesvirus infection, in vivo.
AB  - The oncogenic gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma
      herpesvirus (KSHV), are etiologically associated with a variety of human cancers,
      including Burkitt's lymphoma (BL), Hodgkin lymphoma (HL), Kaposi's sarcoma (KS),
      and primary effusion lymphoma (PEL). Recently, we demonstrated KSHV infection of
      B- and endothelial cells to significantly upregulate the expression of interferon
      induced transmembrane protein 1 (IFITM1) which in turn enhances virus entry. This
      is an extension of the above study. In here, we determined EBV infection of cells
      to trigger IFITM1 expression, in vitro. Silencing IFITM1 expression using siRNA
      specifically lowered gammaherpesvirus infection of cells at a post binding stage
      of entry. A natural model system to explore the effect of IFITM1 on
      gammaherpesvirus infection in vivo is infection of BALB/c mice with murine
      gammaherpesvirus 68 (MHV-68). Priming mice with siRNA specific to IFITM1
      significantly lowered MHV-68 titers in the lung specimens compared to priming
      with (NS)siRNA or PBS. MHV-68 titers were monitored by plaque assay and qPCR.
      Taken together, for the first time, this study provides insight into the critical
      role of IFITM1 to promoting in vivo gammaherpesvirus infections.

PMID- 30237528
TI  - Catalysis at the limit.

PMID- 30237527
TI  - Optogenetic control of epithelial-mesenchymal transition in cancer cells.
AB  - Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms
      in the initiation and promotion of cancer cell metastasis. The phosphoinositide 3
      kinase (PI3K) signaling pathway has been demonstrated to be involved in TGF-beta
      induced EMT, but the complicated TGF-beta signaling network makes it challenging
      to dissect the important role of PI3K on regulation of EMT process. Here, we
      applied optogenetic controlled PI3K module (named 'Opto-PI3K'), which based on
      CRY2 and the N-terminal of CIB1 (CIBN), to rapidly and reversibly control the
      endogenous PI3K activity in cancer cells with light. By precisely modulating the
      kinetics of PI3K activation, we found that E-cadherin is an important downstream
      target of PI3K signaling. Compared with TGF-beta treatment, Opto-PI3K had more
      potent effect in down-regulation of E-cadherin expression, which was demonstrated
      to be regulated in a light dose-dependent manner. Surprisingly, sustained PI3K
      activation induced partial EMT state in A549 cells that is highly reversible.
      Furthermore, we demonstrated that Opto-PI3K only partially mimicked TGF-beta
      effects on promotion of cell migration in vitro. These results reveal the
      importance of PI3K signaling in TGF-beta induced EMT, suggesting other TGF-beta
      regulated signaling pathways are necessary for the full and irreversible
      promotion of EMT in cancer cells. In addition, our study implicates the great
      promise of optogenetics in cancer research for mapping input-output relationships
      in oncogenic pathways.

PMID- 30237529
TI  - Hafnium the lutecium I used to be.

PMID- 30237530
TI  - It's alive!

PMID- 30237531
TI  - A positive positive to negative.

PMID- 30237532
TI  - SNAr stands corrected.

PMID- 30237533
TI  - Anti-inflammatory action of cysteine derivative S-1-propenylcysteine by inducing
      MyD88 degradation.
AB  - The degradation of target proteins by small molecules utilizing the cellular
      proteolytic system is featured as a treatment strategy of several diseases. We
      found that S-1-propenylcysteine (S1PC) among several cysteine derivatives in aged
      garlic extract inhibited TLR-mediated IL-6 production by inducing the degradation
      of adaptor protein MyD88. We showed that S1PC directly denatured MyD88 and
      induced the formation of protein aggregates. Consequently, MyD88 was degraded by
      aggresome-autophagy pathway. On the other hand, S-allylcysteine, a structural
      analog of S1PC, failed to induce the degradation of MyD88 because of its
      inability to denature MyD88 although it also activated autophagy. Our findings
      suggest that S1PC induces MyD88 degradation through the denaturation of MyD88 and
      the activation of autophagy. Thus, S1PC may serve as the base to develop a
      therapeutic means for immune diseases associated with aberrant TLR signaling
      pathways.

PMID- 30237534
TI  - Recurrent large earthquakes related with an active fault-volcano system,
      southwest Japan.
AB  - Based on fieldworks, trench excavation, archaeological evidence, and radiocarbon
      dating ages, we have identified at least three large normal faulting events
      within Aso caldera in the past ~3000 years, excluding the 2016 Mw 7.1 Kumamoto
      earthquake. These events took place in AD ~1000, BC ~100, and BC ~1100,
      respectively, suggesting an average recurrence interval of ~1000 years. These
      events coincide with the timings of three large inferred paleoearthquakes within
      the Hinagu-Futagawa Fault Zone (HFFZ), where the 2016 Kumamoto earthquake rupture
      began. On the basis of geological, geophysical, and seismic data, we conclude
      that the recurrent normal faulting events within Aso caldera were triggered by
      the active faults of the HFFZ. As for the 2016 Kumamoto earthquake, seismic
      rupture initiated on the southwest side of the caldera, propagated northeastward,
      and terminated inside it. These findings demonstrate that large recurring
      earthquakes within an active fault-volcano system can be studied to improve our
      understanding of the termination of coseismic rupture propagation, and that the
      magma chamber beneath Mt. Aso probably hinders the propagation of coseismic
      rupture during large earthquakes.

PMID- 30237535
TI  - First- and second-order contributions to depth perception in anti-correlated
      random dot stereograms.
AB  - The binocular energy model of neural responses predicts that depth from binocular
      disparity might be perceived in the reversed direction when the contrast of dots
      presented to one eye is reversed. While reversed-depth has been found using anti
      correlated random-dot stereograms (ACRDS) the findings are inconsistent across
      studies. The mixed findings may be accounted for by the presence of a gap between
      the target and surround, or as a result of overlap of dots around the vertical
      edges of the stimuli. To test this, we assessed whether (1) the gap size (0, 19.2
      or 38.4 arc min) (2) the correlation of dots or (3) the border orientation
      (circular target, or horizontal or vertical edge) affected the perception of
      depth. Reversed-depth from ACRDS (circular no-gap condition) was seen by a
      minority of participants, but this effect reduced as the gap size increased.
      Depth was mostly perceived in the correct direction for ACRDS edge stimuli, with
      the effect increasing with the gap size. The inconsistency across conditions can
      be accounted for by the relative reliability of first- and second-order depth
      detection mechanisms, and the coarse spatial resolution of the latter.

PMID- 30237536
TI  - Separation of blood microsamples by exploiting sedimentation at the microscale.
AB  - Microsample analysis is highly beneficial in blood-based testing where cutting
      edge bioanalytical technologies enable the analysis of volumes down to a few tens
      of microliters. Despite the availability of analytical methods, the difficulty in
      obtaining high-quality and standardized microsamples at the point of collection
      remains a major limitation of the process. Here, we detail and model a blood
      separation principle which exploits discrete viscosity differences caused by
      blood particle sedimentation in a laminar flow. Based on this phenomenon, we
      developed a portable capillary-driven microfluidic device that separates blood
      microsamples collected from finger-pricks and delivers 2 uL of metered serum for
      bench-top analysis. Flow cytometric analysis demonstrated the high purity of
      generated microsamples. Proteomic and metabolomic analyses of the microsamples of
      283 proteins and 1351 metabolite features was consistent with samples generated
      via a conventional centrifugation method. These results were confirmed by a
      clinical study scrutinising 8 blood markers in obese patients.

PMID- 30237537
TI  - The Value of Decreased Thyroid Hormone for Predicting Mortality in Adult Septic
      Patients: A Systematic Review and Meta-Analysis.
AB  - Decreased thyroid hormone (TH) has been considered as one of the potential
      predictors of mortality in sepsis. This study aimed to evaluate the prognostic
      impact of decreased TH on mortality in septic patients during intensive care unit
      (ICU) admission. We included studies that assessed thyroid function by measuring
      the serum thyroid hormone level and in-hospital mortality in adult septic
      patients. Reviews, case reports, editorials, letters, commentaries, animal
      studies, duplicate studies, and studies with irrelevant populations and
      inappropriate controls were excluded. A total of 1,578 patients from eight
      studies were included. Triiodothyronine levels in non-survivors were relatively
      lower than that of survivors (6 studies; standardized mean difference [SMD] 2.31;
      95% confidence interval (CI), 0.52-4.10; I2 = 97%; P = 0.01). Thyroxine levels in
      non-survivors were also lower than that of survivors (5 studies; SMD 2.40; 95%
      CI, 0.91-3.89). There were no statistically significant differences in thyroid
      stimulating hormone levels between non-survivors and survivors. The present meta
      analysis suggested that the decreased TH during ICU admission might be associated
      with the increase in mortality in adult septic patients. Hence, the measurement
      of TH could provide prognostic information on mortality in adult septic patients.

PMID- 30237539
TI  - HP1 cooperates with CAF-1 to compact heterochromatic transgene repeats in
      mammalian cells.
AB  - The nuclear organization of tightly condensed heterochromatin plays important
      roles in regulating gene transcription and genome integrity. Heterochromatic
      domains are usually present at chromosomal regions containing a large array of
      repeated DNA sequences. We previously showed that integration of a 1,000-copy
      tandem array of an inducible reporter gene into the genome of mammalian cells
      induces the formation of a highly compact heterochromatic domain enriched in
      heterochromatin protein 1 (HP1). It remains to be determined how these DNA
      repeats are packaged into a heterochromatic form and are silenced. Here, we show
      that HP1-mediated transgene condensation and silencing require the interaction
      with PxVxL motif-containing proteins. The chromatin assembly factor 1 (CAF-1)
      complex concentrates at the transgenic locus through the interaction of its PxVxL
      motif-containing p150 subunit with HP1. Knockdown of p150 relieves HP1-mediated
      transgene compaction and repression. When targeted to the transgenic locus, p150
      mutants defective in binding HP1 cause transgene decondensation and activation.
      Taken together, these results suggest that HP1 cooperates with CAF-1 to compact
      transgene repeats. This study provides important insight into how heterochromatin
      is maintained at chromosomal regions with abundant DNA repeats.

PMID- 30237538
TI  - Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by
      inhibiting the autophagic-inflammasomal pathway.
AB  - Arsenic exposure causes nonalcoholic steatohepatitis (NASH). Inflammation is a
      key contributor to the pathology of nonalcoholic fatty liver disease (NAFLD),
      including NASH. However, it is unclear how arsenic induces inflammation. In mouse
      livers, we show that arsenic trioxide (As2O3) induced NASH, increased autophagy
      and NLRP3 inflammasome activation, increased lipid accumulation, and resulted in
      dysregulation of lipid-related genes. Supplemented with taurine (Tau) attenuated
      the inflammation and autophagy caused by As2O3. In HepG2 cells, we found that
      As2O3-induced pyroptotic cell death was dependent upon the activation of NLRP3
      inflammasome, which was CTSB-dependent. In addition, inhibiting autophagy
      alleviated the As2O3-induced increase of cytosolic CTSB expression and subsequent
      release of LDH, activation of the NLRP3 inflammasome, and pyroptosis. Moreover,
      we found that Tau alleviated As2O3-induced elevation of autophagy, CTSB
      expression, and activation of the NLRP3 inflammasome, and reduced the release of
      LDH, pyroptotic cell death, and inflammation. Interestingly, As2O3-induced lipid
      accumulation could not be alleviated by either inhibition of autophagy nor by
      inhibition of CTSB. Additionally, neither inhibition of the NLRP3 inflammasome or
      Tau treatment could alleviate lipid accumulation. These results demonstrated that
      As2O3-induced pyroptosis involves autophagy, CTSB, and the NLRP3 inflammasome
      cascade, and that Tau alleviates As2O3-induced liver inflammation by inhibiting
      the autophagic-CTSB-NLRP3 inflammasomal pathway rather than decreasing lipid
      accumulation. These findings give insight into the association of autophagy,
      inflammation, pyroptosis, and NASH induced by As2O3.

PMID- 30237541
TI  - Challenges in managing graft-versus-host disease in developing countries: a
      perspective.
AB  - Hematopoietic cell transplant (HCT) activity is increasing worldwide due to safer
      techniques, widening indications, and more availability of donors. New HCT
      centers have recently been established in many developing countries including
      Asian and African countries. Due to limited resources, logistic, political, and
      social issues in developing countries, the treatment of orphan diseases like
      graft-versus-host disease (GVHD) can be challenging. We intended to delineate the
      current issues that institutions and clinicians face in managing GVHD. We
      conducted a comprehensive systematic electronic review of peer-reviewed published
      articles on GVHD management in developing countries. We used PubMed, Cochrane,
      and Embase databases as our primary source of data. Studies that were included
      described the treatments for both acute and chronic GVHD. Consensus on the use of
      high-dose methyl-prednisone and prednisolone as the initial therapy was widely
      accepted and used in practice. Socio-economic factors were found to be the major
      factor involved in GVHD management in lower income patients. Delayed diagnosis
      and treatment, lack of availability of healthcare professionals, lack of
      knowledge among cancer patients, and poverty are major concerns in the developing
      world. For optimal management, HCT programs should develop systems in place for
      long-term follow-up of HCT survivors and have a low threshold to initiate
      treatments for GVHD early. Awareness and health policy programs must be initiated
      at the grass-root level for long-term management of these survivors in developing
      countries.

PMID- 30237542
TI  - Words affect visual perception by activating object shape representations.
AB  - Linguistic labels are known to facilitate object recognition, yet the mechanism
      of this facilitation is not well understood. Previous psychophysical studies have
      suggested that words guide visual perception by activating information about
      visual object shape. Here we aimed to test this hypothesis at the neural level,
      and to tease apart the visual and semantic contribution of words to visual object
      recognition. We created a set of object pictures from two semantic categories
      with varying shapes, and obtained subjective ratings of their shape and category
      similarity. We then conducted a word-picture matching experiment, while recording
      participants' EEG, and tested if the shape or the category similarity between the
      word's referent and target picture explained the spatiotemporal pattern of the
      picture-evoked responses. The results show that hearing a word activates
      representations of its referent's shape, which interacts with the visual
      processing of a subsequent picture within 100 ms from its onset. Furthermore, non
      visual categorical information, carried by the word, affects the visual
      processing at later stages. These findings advance our understanding of the
      interaction between language and visual perception and provide insights into how
      the meanings of words are represented in the brain.

PMID- 30237540
TI  - p53 cooperates with SIRT6 to regulate cardiolipin de novo biosynthesis.
AB  - The tumor suppressor p53 has critical roles in regulating lipid metabolism, but
      whether and how p53 regulates cardiolipin (CL) de novo biosynthesis is unknown.
      Here, we report that p53 physically interacts with histone deacetylase SIRT6 in
      vitro and in vivo, and this interaction increases following palmitic acid (PA)
      treatment. In response to PA, p53 and SIRT6 localize to chromatin in a p53
      dependent manner. Chromatin p53 and SIRT6 bind the promoters of CDP
      diacylglycerol synthase 1 and 2 (CDS1 and CDS2), two enzymes required to catalyze
      CL de novo biosynthesis. Here, SIRT6 serves as a co-activator of p53 and
      effectively recruits RNA polymerase II to the CDS1 and CDS2 promoters to enhance
      CL de novo biosynthesis. Our findings reveal a novel, cooperative model executed
      by p53 and SIRT6 to maintain lipid homeostasis.

PMID- 30237543
TI  - Author Correction: Drug-mediated metabolic tipping between antibiotic resistant
      states in a mixed-species community.
AB  - In the version of this Article originally published, the following sentence was
      missing from the Acknowledgements: "R.E.B. is an EPSRC Healthcare Technologies
      Impact Fellow EP/N033671/1; I.G. is funded by ERC Consolidator grant 647292
      MathModExp; A.J.P.B., N.A.R.G. and A.T. were funded by BBSRC grant BB/F00513X/1;
      K.H., I.G., S.N. and E.C. were funded by BBSRC grant BB/F005210/2." This text has
      now been added.

PMID- 30237544
TI  - Molecular mechanism of the Escherichia coli AhpC in the function of a chaperone
      under heat-shock conditions.
AB  - Peroxiredoxins (Prxs) are ubiquitous antioxidants utilizing a reactive cysteine
      for peroxide reduction and acting as a molecular chaperone under various stress
      conditions. Besides other stimulating factors, oxidative- and heat stress
      conditions trigger their ATP-independent chaperoning function. So far, many
      studies were intended to reveal the chaperoning mechanisms of the so-called
      sensitive Prxs of eukaryotes, which are susceptible to inactivation by over
      oxidation of its reactive cysteine during H2O2 reduction. In contrast, the
      chaperone mechanisms of bacterial Prxs, which are mostly robust against
      inactivation by over-oxidation, are not well understood. Herein, comprehensive
      biochemical and biophysical studies demonstrate that the Escherichia coli alkyl
      hydroperoxide reductase subunit C (EcAhpC) acquires chaperone activity under heat
      stress. Interestingly, their chaperoning activity is independent of its redox
      states but is regulated in a temperature-dependent manner. Data are presented,
      showing that oxidized EcAhpC, which forms dimers at 25  degrees C, self-assembled
      into high molecular weight (HMW) oligomers at higher temperatures and supressed
      aggregation of client proteins at heat-shock conditions. In addition, we
      unravelled the essential role of the C-terminal tail of EcAhpC on heat-induced
      HMW oligomer formation and chaperoning activity. Our findings suggest a novel
      molecular mechanism for bacterial Prxs to function as chaperone at heat-shock
      conditions.

PMID- 30237545
TI  - CPEB1 mediates hepatocellular carcinoma cancer stemness and chemoresistance.
AB  - Cancer stem cells (CSCs) are a subpopulation of cells within tumors that are
      believed to possess pluripotent properties and thought to be responsible for
      tumor initiation, progression, relapse and metastasis. Cytoplasmic
      polyadenylation element-binding protein 1 (CPEB1), a sequence-specific RNA
      binding protein that regulates mRNA polyadenylation and translation, has been
      linked to cancer progression and metastasis. However, the involvement of CPEB1 in
      hepatocellular carcinoma (HCC) remains unclear. In this study, we have
      demonstrated that CPEB1 directly regulates sirtuin 1 (SIRT1) mRNA to mediate
      cancer stemness in HCC. Cancer stemness was analyzed by self-renewal ability,
      chemoresistance, metastasis, expression of stemness-related genes and CSC marker
      positive cell populations. The results indicate that CPEB1 is downregulated in
      HCC. Overexpression of CPEB1 dramatically reduced HCC cell stemness, whereas
      silencing CPEB1 enhances it. Using site-directed mutagenesis, a luciferase
      reporter assay, and immunoprecipitation, we found that CPEB1 could directly
      target the 3'-UTR of SIRT1, control poly(A) tail length and suppress its
      translation to mediate cancer stemness in vitro and in vivo. Overall, our
      findings suggest that the negative regulation between CPEB1 and SIRT1 contributes
      to the suppression of cancer stemness in HCC. CPEB1 may have potential as a
      therapeutic target in HCC.

PMID- 30237547
TI  - Publisher Correction: Ancient DNA from Chalcolithic Israel reveals the role of
      population mixture in cultural transformation.
AB  - In the original version of this Article, references in the format 'First author
      et al.' were inappropriately deleted. These errors have been corrected in the PDF
      and HTML versions of the Article.

PMID- 30237548
TI  - Patient perspectives on Peyronie's disease: results of poststudy interviews from
      a phase 2 trial of collagenase clostridium histolyticum.
AB  - Intralesional injection of collagenase clostridium histolyticum (CCH) improves
      Peyronie's disease (PD) symptoms; however, patient perspectives regarding PD and
      CCH treatment have not been fully elucidated. This cross-sectional qualitative
      study included heterosexual men with PD who received >=1 injection of study
      medication and had >=1 posttreatment Peyronie's Disease Questionnaire (PDQ)
      assessment during a prior phase 2b clinical trial. These patients were
      "responders" if they reported (as part of the Global Assessment of the PDQ) that
      overall symptoms and effects of PD had at least "improved in a small but
      important way" after CCH therapy. Among 45 patients interviewed, penile bending
      or curvature was the most common and bothersome PD symptom reported (by 97.8% and
      48.9% of patients, respectively). Patients indicated that multiple alterations
      were necessary in their sex lives because of penile symptoms and specified that
      these changes impacted their emotional health and partner relationship. Treatment
      with CCH improved PD symptoms (44.4%), frequency of or ability to have vaginal
      intercourse (22.2%) and partner relationship (22.2%), particularly among
      responders. Given that physical, psychologic and sexual function are impacted by
      PD, clinical trials that evaluate treatments for PD should include patient
      reported outcome measures (e.g., the PDQ) to assess overall well-being after
      treatment.

PMID- 30237546
TI  - Neuroglobin promotes neurogenesis through Wnt signaling pathway.
AB  - Neuroglobin (Ngb) has been demonstrated by our lab and others to be
      neuroprotective against neurological disorders including stroke. However, the
      roles of Ngb in neurogenesis remain elusive. Neurogenesis can occur in adulthood
      and can be induced by pathological conditions in the brain such as stroke, and
      significantly contributes to functional recovery, thus enhancing endogenous
      neurogenesis may be a promising therapeutic strategy for neurodegenerative
      diseases. In this study we aimed to investigate the roles of Ngb in neurogenesis
      using Lentivirus overexpressing Ngb (Lv-Ngb). We show that Ngb overexpression
      promoted the proliferation of neural progenitor cells (NPC) marked by increased
      neurosphere number and size. Ngb overexpression also enhanced neuronal
      differentiation of cultured NPC under differentiation conditions. Moreover,
      subventricular injection of Lv-Ngb in mice after middle cerebral artery occlusion
      (MCAO) increased PSA-NCAM positive neuroblastoma cells and Tuj1 positive immature
      neurons, suggesting that Ngb overexpression promotes neurogenesis in mice brain
      after stroke. We further show that the pro-neurogenesis effect of Ngb
      overexpression might be mediated through Dvl1 up-regulation, and subsequent
      activation of Wnt signaling, indicated by increased nuclear localization of beta
      catenin. These results suggest that Ngb may play an important role in promoting
      neurogenesis in neurodegenerative diseases such as stroke, which may eventually
      benefit the development of stroke therapeutics targeting neurogenesis through Ngb
      upregulation.

PMID- 30237550
TI  - Developing a geostatistical simulation method to inform the quantity and
      placement of new monitors for a follow-up air sampling campaign.
AB  - Sampling campaign design is a crucial aspect of air pollution exposure studies.
      Selection of both monitor numbers and locations is important for maximizing
      measured information, while minimizing bias and costs. We developed a two-stage
      geostatistical-based method using pilot NO2 samples from Lanzhou, China with the
      goal of improving sample design decision-making, including monitor numbers and
      spatial pattern. In the first step, we evaluate how additional monitors change
      prediction precision through minimized kriging variance. This was assessed in a
      Monte Carlo fashion by adding up to 50 new monitors to our existing sites with
      assigned concentrations based on conditionally simulated NO2 surfaces. After
      identifying a number of additional sample sites, a second step evaluates their
      potential placement using a similar Monte Carlo scheme. Evaluations are based on
      prediction precision and accuracy. Costs are also considered in the analysis. It
      was determined that adding 28-locations to the existing Lanzhou NO2 sampling
      campaign captured 73.5% of the total kriged variance improvement and resulted in
      predictions that were on average within 10.9 MUg/m3 of measured values, while
      using 56% of the potential budget. Additional monitor sites improved kriging
      variance in a nonlinear fashion. This method development allows for informed
      sampling design by quantifying prediction improvement (accuracy and precision)
      against the costs of monitor deployment.

PMID- 30237549
TI  - Rechargeable potassium-ion batteries with honeycomb-layered tellurates as high
      voltage cathodes and fast potassium-ion conductors.
AB  - Rechargeable potassium-ion batteries have been gaining traction as not only
      promising low-cost alternatives to lithium-ion technology, but also as high
      voltage energy storage systems. However, their development and sustainability are
      plagued by the lack of suitable electrode materials capable of allowing the
      reversible insertion of the large potassium ions. Here, exploration of the
      database for potassium-based materials has led us to discover potassium ion
      conducting layered honeycomb frameworks. They show the capability of reversible
      insertion of potassium ions at high voltages (~4 V for K2Ni2TeO6) in stable ionic
      liquids based on potassium bis(trifluorosulfonyl) imide, and exhibit remarkable
      ionic conductivities e.g. ~0.01 mS cm-1 at 298 K and ~40 mS cm-1 at 573 K for
      K2Mg2TeO6. In addition to enlisting fast potassium ion conductors that can be
      utilised as solid electrolytes, these layered honeycomb frameworks deliver the
      highest voltages amongst layered cathodes, becoming prime candidates for the
      advancement of high-energy density potassium-ion batteries.

PMID- 30237551
TI  - Passive indoor air sampling for consumer product chemicals: a field evaluation
      study.
AB  - Innovative exposure measurement methods are needed for large environmental health
      studies, particularly for semivolatile organic compounds (SVOCs). Active air
      sampling methods are costly to implement, but passive air sampling presents a
      viable method. To expand and improve the use of passive air samplers (PAS) for
      indoor SVOC monitoring, we designed a unique, compact sampler using commercially
      available polyurethane foam (PUF) disks housed within durable, easy-to-setup, low
      profile enclosures. We evaluated the new design using co-located active air
      samplers (AAS) and analyzed for SVOCs. Most of the targeted SVOCs found using
      active sampling (27 of 33) were also detected using passive sampling. We found
      good agreement (R2 = 0.88) between active and passive sampling methods for
      characterizing the relative abundance of each chemical, and the measured active
      sampler concentrations and passive sampler masses were significantly positively
      correlated for 14 of 21 chemicals, for which correlations could be estimated. We
      found that measurements of many SVOCs originating from consumer products and
      typically found in the gas-phase (log KOA < 10) can be reliably ranked-and thus
      appropriate for epidemiological studies-using this PAS design. These SVOCs
      include diethyl phthalate, AHTN, HHCB, tris(2-chloroethyl) phosphate, dibutyl
      phthalate, and tris(1-chloro-2-propyl) phosphate, as well as methyl paraben,
      benzophenone, and benzophenone-3, which have not previously been measured by
      passive sampling. This PAS can be used in epidemiological studies involving
      consumer product chemicals and complements other novel exposure tools.

PMID- 30237552
TI  - Effect on Local Structure and Phase Transition of Perovskite-Type [N(CH3)4]2Zn1
      xCuxBr4 (x = 0, 0.5, 0.7, and 1) Crystals with the Various Doping of Cu2+ Ions.
AB  - This study focused on how the local structures in pure [N(CH3)4]2ZnBr4 crystal
      are affected by the partial replacement of Zn2+ ions with Cu2+ ions. The
      structures and phase transition temperatures TC of perovskite-type [N(CH3)4]2Zn1
      xCuxBr4 (x = 0, 0.5, 0.7, and 1) mixed crystals were almost unchanged by the
      partial doping of Cu2+ ions. The environments for the local structures of
      [N(CH3)4]2Zn1-xCuxBr4 mixed systems were studied according to differences in the
      chemical shifts of the 1H magic angle spinning (MAS) NMR, 13C cross-polarization
      (CP)/MAS NMR, and 14N NMR spectra. The 1H and 13C NMR results showed that the
      local environments of 1H and 13C nuclei near TC are not affected by substituting
      Zn2+ ions with Cu2+ ions, whereas the 14N NMR results showed that the local
      environment is affected near TC. Consequently, the main indicators of the phase
      transition in [N(CH3)4]2Zn1-xCuxBr4 are related to the ferroelastic
      characteristics with different orientations.

PMID- 30237553
TI  - CRISPR therapy shows promise in Duchenne muscular dystrophy.

PMID- 30237554
TI  - Sleep bruxism: an overview for clinicians.
AB  - Bruxism is characterised by clenching or grinding of the teeth due to contraction
      of the masseter, temporalis and other jaw muscles. Bruxism may lead to
      masticatory muscle hypertrophy, tooth surface loss, fracture of restorations or
      teeth, hypersensitive or painful teeth and loss of periodontal support. Sleep
      bruxism has previously been viewed as a dysfunctional movement or pathological
      condition, whereas it is now accepted as a centrally controlled condition with
      various systemic risk factors. It has been postulated that sleep bruxism may have
      a protective role during sleep, for example in relation to airway maintenance or
      in stimulating saliva flow. A diagnosis of sleep bruxism may be made via patient
      report and clinical interview, clinical examination, intraoral appliances or
      recording of muscle activity. Bruxism in itself does not require treatment:
      management is only indicated where problems arise as a result of bruxism. Oral
      appliances primarily aim to protect the dentition from damage caused by
      clenching/grinding, although they may reduce muscle activity. Irreversible
      occlusal adjustments have no basis in evidence in the management of bruxism.
      Behavioural strategies include biofeedback, relaxation and improvement of sleep
      hygiene. Administration of botulinum toxin (Botox) to the masticatory muscles
      appears to reduce the frequency of bruxism, but concerns have been raised
      regarding possible adverse effects. Dentists should be aware of the potential
      aetiology, pathophysiology and management strategies of sleep bruxism.

PMID- 30237555
TI  - Introduction of a head and neck cancer dental screening pro forma.

PMID- 30237556
TI  - Inside information.
AB  - Primary care dentistry is very different from most other parts of healthcare, for
      a combination of reasons which very few people outside dentistry recognise and
      understand. This has many undesirable and sometimes serious consequences for
      dental practitioners. This article argues that unless the views and first-hand
      experience of dentists is respected and valued, dentists and dentistry will
      always come off second best when set against the massive scale of medicine, and
      wider health and social care.

PMID- 30237559
TI  - Trade-Off Analysis to Determine Environmental Flows in a Highly Regulated
      Watershed.
AB  - In this study, we proposed an approach to recommend environmental flows in highly
      regulated areas, considering the multiple time scales of hydrological processes
      and water requirements. Water resources were seasonally allocated to the
      agricultural sector using a benefit-maximizing model, based on water deficiency
      at different crop growth stages. The economic feedback was evaluated after
      securing different levels of initial environmental flows. The final environmental
      flows were recommended to maintain a balance between the ecosystem and irrigation
      water needs. A case study was applied in the Baiyangdian watershed, China. The
      results show that a benefit-maximizing model can reduce the total economic losses
      to the maximum potential, which contributes to alleviating water use conflicts
      between agriculture and the ecosystem. However, the environmental flows cannot be
      maintained without the sacrifice of production losses, except for in extremely
      wet years. Average environmental flows could be secured at around 3.1, 4.3 and
      5.4 * 108 m3 in dry, average, and wet years, respectively, with less than 10%
      production loss. Additional water transfer projects, as well as economic
      compensation strategies, are suggested to meet both ecosystem and agricultural
      needs. The planned economic compensation during 2010-2015 was 16.3 * 108 Yuan,
      giving priority to securing environmental flows, and accounting for 7% of the
      total agricultural output value. The suggested amount of water resource
      transferred by the South-to-North Transfer Projects was 19 * 108 m3, which is
      enough to alleviate water use conflicts between different stakeholders in dry
      years. This study provided a method to protect ecosystems in a more sustainable
      way.

PMID- 30237558
TI  - Enhanced antibacterial effect of the novel T4-like bacteriophage KARL-1 in
      combination with antibiotics against multi-drug resistant Acinetobacter
      baumannii.
AB  - The continuing rise of infections caused by multi-drug resistant bacteria has led
      to a renewed interest in bacteriophage therapy. Here we characterize phage
      vB_AbaM-KARL-1 with lytic activity against multi-drug resistant clinical isolates
      of Acinetobacter baumannii (AB). Besides genomic and phenotypic phage analysis,
      the objective of our study was to investigate the antibacterial outcome when the
      phage acts in concert with distinct antibiotics. KARL-1 belongs to the family of
      Myoviridae and is able to lyse 8 of 20 (40%) tested clinical isolates. Its double
      stranded DNA genome consists of 166,560 bp encoding for 253 open reading frames.
      Genome wide comparison suggests that KARL-1 is a novel species within the
      subfamily Tevenvirinae, sharing 77% nucleotide identity (coverage 58%) with phage
      ZZ1. The antibacterial efficacy at various multiplicities of infection (MOI) was
      monitored either alone or in combination with meropenem, ciprofloxacin, and
      colistin. A complete clearance of liquid cultures was achieved with KARL-1 at an
      MOI of 10-1 and meropenem (>128 mg/l). KARL-1 was still effective at an MOI of 10
      7, but antibacterial activity was significantly augmented with meropenem. While
      ciprofloxacin did generally not support phage activity, the application of KARL-1
      at an MOI of 10-7 and therapeutic doses of colistin significantly elevated
      bacterial suppression. Hence, KARL-1 represents a novel candidate for use against
      multi-drug resistant AB and the therapeutic outcome may be positively influenced
      by the addition of traditional antibiotics.

PMID- 30237557
TI  - Evaluation of the roles of the cytosolic N-terminus and His-rich loop of ZNT
      proteins using ZNT2 and ZNT3 chimeric mutants.
AB  - The physiological roles of Zn transporter (ZNT) proteins are being increasingly
      recognized, and three dimensional structures of ZNT bacterial homologs have
      facilitated our understanding of their biochemical characteristics at the
      molecular level. However, the biological role of the unique structural features
      of vertebrate ZNTs, which are absent in their bacterial homologues, is not
      completely understood. These ZNT sequences include a cytosolic His-rich loop
      between transmembrane helices IV and V and the cytosolic N-terminus. This study
      investigated the contribution of these features to zinc transport by ZNT
      proteins. The importance of the His residues in the cytosolic His-rich loop was
      investigated using ZNT2 Ala substitution and deletion mutants. The presence of
      His residues was not essential for zinc transport, even though they possibly
      participate in modulation of zinc transport activity. Furthermore, we determined
      the role of the N-terminus by characterizing ZNT2 and ZNT3 domain-swapped and
      deletion mutants. Unexpectedly, the N-terminus was also not essential for zinc
      transport by ZNT2 and the domain-swapped ZNT2 mutant, in which the cytosolic His
      rich loop was substituted with that of ZNT3. These results provide molecular
      insights into understanding the roles of the cytosolic parts of ZNT2, ZNT3, and
      probably other members of their subgroup.

PMID- 30237560
TI  - Ultrafast Volumetric Optoacoustic Imaging of Whole Isolated Beating Mouse Heart.
AB  - The Langendorff-perfused heart technique has become the model of choice for
      multiparametric optical mapping of cardiac function and electrophysiology.
      However, photon scattering in tissues represents a significant drawback of the
      optical imaging approach, fundamentally limiting its mapping capacity to the
      heart surface. This work presents the first implementation of the optoacoustic
      approach for 4D imaging of the entire beating isolated mouse heart. The method
      combines optical excitation and acoustic detection to simultaneously render rich
      optical contrast and high spatio-temporal resolution at centimeter-scale depths.
      We demonstrate volumetric imaging of deeply located cardiac features, including
      the interventricular septum, chordae tendineae, and papillary muscles while
      further tracking the heart beat cycle and the motion of the pulmonary, mitral,
      and tricuspid valves in real time. The technique possesses a powerful combination
      between high imaging depth, fast volumetric imaging speed, functional and
      molecular imaging capacities not available with other imaging modalities
      currently used in cardiac research.

PMID- 30237562
TI  - Microbial communities in different regions of the gastrointestinal tract in East
      Asian finless porpoises (Neophocaena asiaeorientalis sunameri).
AB  - Mammalian gastrointestinal (GI) tract microbial communities are critical for host
      health. However, the microbiota along the GI tract in cetaceans has not been well
      characterized compared to other animals. In this study, the bacteria and fungi
      present in the stomach, foregut, hindgut and feces, of East Asian finless
      porpoises (Neophocaena asiaeorientalis sunameri, EAFPs) were characterized using
      high-throughput sequencing analysis. The bacterial and fungal diversity and
      richness in the stomach, hindgut and fecal samples tended to be higher than those
      in the foregut. Bacterial taxonomic compositions found in the hindgut and feces
      were different from those seen in the stomach and foregut. A greater proportion
      of strict anaerobic bacteria including Clostridia, Fusobacteria, and
      Ruminococcaceae were found in the hindgut and fecal samples. The fungal
      communities present in stomach samples differed from those detected in other
      regions to some extent. Zygomycota and Neocallimastigomycota were more
      predominant in the stomach. Some potential pathogens, such as Helicobacter spp.
      and Vibrio spp., were commonly present along the GI tract. Our study confirms
      that the fecal microbiota can represent the whole GI tract to some extent because
      of their relatively higher microbial diversity and presence of potential
      pathogens. Our study provides the first comprehensive characterization of the
      EAFPs GI microbiota, expanding on the current knowledge about the bacterial
      diversity in the GI tract of cetaceans. In addition, this is the first study
      characterizing the fungal diversity of any species of porpoise.

PMID- 30237561
TI  - Aberrant activation of Notch-1 signaling inhibits podocyte restoration after
      islet transplantation in a rat model of diabetic nephropathy.
AB  - Signaling abnormalities play important roles during podocyte injury and have been
      indicated as crucial events for triggering many glomerular diseases. There is
      emerging evidence demonstrating significant improvements in preventing renal
      injury and restoring podocytes after islet transplantation. However, whether
      signaling abnormalities affect the therapeutic efficacy of islet transplantation
      remain unclear. This study was established to investigate the impact of Notch-1
      signaling activation on renal injury and podocyte restoration after islet
      transplantation. Experiments were performed in vivo and in vitro under conditions
      of diabetic nephropathy and high-glucose medium, respectively. Podocyte injury in
      vitro was induced by high-glucose concentration, and expression levels of genes
      associated with the Notch-1 pathway were also regulated by Jagged-1/FC and N-[N
      (3,5-Difluorophenacetyl)-L-alanyl]- S-phenylglycine t-butyl ester (DAPT).
      Podocytes were co-cultured with islets to investigate the protective effect of
      islets in high-glucose conditions. Histopathological staining and transmission
      electron microscopy were performed to assess pathological changes in podocytes in
      glomeruli. The results from this study showed that Notch-1 signaling in podocytes
      was significantly decreased by functional islet cells in vivo and in vitro.
      Compared with the co-cultured group and transplanted group, highly activated
      Notch-1 signaling significantly moderated the effect of islets in affecting
      podocyte restoration and renal injury. Renal damage and podocyte injury were
      alleviated after DAPT treatment. Furthermore, the balance between apoptosis and
      autophagy was diverse under different treatments. All the data in this study
      showed that highly activated Notch-1 signaling could affect the therapeutic
      efficacy of islet transplantation on renal injury and podocyte restoration in
      high-glucose conditions. The balance between apoptosis and autophagy was also
      closely associated with the degree of podocyte restoration. This finding may
      suggest that the in vivo microenvironment plays a critical role in podocyte
      restoration after islet transplantation, which provides a promising and
      individual assessment and targeting treatment for different diabetic nephropathy
      patients after islet transplantation into the future.

PMID- 30237563
TI  - Promoted Angiogenesis and Osteogenesis by Dexamethasone-loaded Calcium Phosphate
      Nanoparticles/Collagen Composite Scaffolds with Microgroove Networks.
AB  - Reconstruction of large bone defects remains a clinical challenge because current
      approaches involving surgery and bone grafting often do not yield satisfactory
      outcomes. For artificial bone substitutes, angiogenesis plays a pivotal role to
      achieve the final success of newly regenerated bone. In this study, dexamethasone
      loaded biphasic calcium phosphate nanoparticles/collagen composite scaffolds with
      several types of concave microgrooves were prepared for simultaneous promotion of
      angiogenesis and osteogenesis. Microgrooves in the scaffolds were supposed to
      guide the assembly of human umbilical vascular endothelial cells (HUVECs) into
      well aligned tubular structures, thus promoting rapid angiogenesis. The scaffolds
      were used for co-culture of HUVECs and human bone marrow-derived mesenchymal stem
      cells. Subcutaneous implantation in mice showed that more blood vessels and newly
      formed bone were observed in the microgrooved composite scaffolds than in the
      control scaffold. Scaffold bearing parallel microgrooves with a concave width of
      290 um and a convex ridge width of 352 um showed the highest promotion effect on
      angiogenesis and osteogenesis among the parallelly microgrooved composite
      scaffolds. The scaffolds bearing a grid network had further superior promotion
      effect to the scaffolds bearing parallel microgrooves. The results indicated that
      microgrooves in the composite scaffolds facilitated angiogenesis and stimulated
      new bone formation. The microgrooved composite scaffolds should be useful for
      repairing of large bone defects.

PMID- 30237565
TI  - Direct-fed microbial supplementation influences the bacteria community
      composition of the gastrointestinal tract of pre- and post-weaned calves.
AB  - This study investigated the effect of supplementing the diet of calves with two
      direct fed microbials (DFMs) (Saccharomyces cerevisiae boulardii CNCM I-1079
      (SCB) and Lactobacillus acidophilus BT1386 (LA)), and an antibiotic growth
      promoter (ATB). Thirty-two dairy calves were fed a control diet (CTL)
      supplemented with SCB or LA or ATB for 96 days. On day 33 (pre-weaning, n = 16)
      and day 96 (post-weaning, n = 16), digesta from the rumen, ileum, and colon, and
      mucosa from the ileum and colon were collected. The bacterial diversity and
      composition of the gastrointestinal tract (GIT) of pre- and post-weaned calves
      were characterized by sequencing the V3-V4 region of the bacterial 16S rRNA gene.
      The DFMs had significant impact on bacteria community structure with most changes
      associated with treatment occurring in the pre-weaning period and mostly in the
      ileum but less impact on bacteria diversity. Both SCB and LA significantly
      reduced the potential pathogenic bacteria genera, Streptococcus and Tyzzerella_4
      (FDR <= 8.49E-06) and increased the beneficial bacteria, Fibrobacter (FDR <=
      5.55E-04) compared to control. Other potential beneficial bacteria, including
      Rumminococcaceae UCG 005, Roseburia and Olsenella, were only increased (FDR <=
      1.30E-02) by SCB treatment compared to control. Furthermore, the pathogenic
      bacterium, Peptoclostridium, was reduced (FDR = 1.58E-02) by SCB only while LA
      reduced (FDR = 1.74E-05) Ruminococcus_2. Functional prediction analysis suggested
      that both DFMs impacted (p < 0.05) pathways such as cell cycle, bile secretion,
      proteasome, cAMP signaling pathway, thyroid hormone synthesis pathway and
      dopaminergic synapse pathway. Compared to the DFMs, ATB had similar impact on
      bacterial diversity in all GIT sites but greater impact on the bacterial
      composition of the ileum. Overall, this study provides an insight on the bacteria
      genera impacted by DFMs and the potential mechanisms by which DFMs affect the GIT
      microbiota and may therefore facilitate development of DFMs as alternatives to
      ATB use in dairy calf management.

PMID- 30237564
TI  - Arsenic circumvents the gefitinib resistance by binding to P62 and mediating
      autophagic degradation of EGFR in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is characterized by hyperexpression and/or
      gain-of-function mutations of the epidermal growth factor receptor (EGFR),
      resulting in an elevated overall kinase activity. Gefitinib is remarkably
      effective in patients with the L858R or DeltaE746-A750-mutated of EGFR. However,
      drug resistance tends to develop because of the emergence of T790M mutation on
      EGFR. New strategies other than repressing kinase activity are thus required to
      treat NSCLC, thereby circumventing the resistance. In this study, arsenic
      trioxide (ATO) at 2 MUM significantly inhibited the proliferation of the
      gefitinib-resistant NCI-H1975 cells of the EGFR L858R/T790M mutant compared with
      a modest inhibition in the gefitinib-sensitive HCC827 cells of DeltaE746-A750
      mutant and A549 cells of wild-type EGFR. Moreover, ATO significantly inhibited
      the overall kinase activity of EGFR primarily through quantitatively diminishing
      the EGFR in NCI-H1975 cells to an extent comparable with that reached by
      gefitinib in HCC827 cells. Furthermore, ATO promoted autophagic degradation of
      EGFR in NSCLC cells by directly binding to P62, which interacted with EGFR,
      preferentially the L858R/T790M mutant providing a plausible explanation for a
      more favorable effect of ATO on NCI-H1975 cells. Accordingly, the effect of ATO
      was further confirmed in the NSCLC xenograft mouse models. Our results reveal a
      new target for ATO with a unique molecular mechanism, i.e., ATO suppresses the
      overall catalytic potential of EGFR, significantly those with the L858R/T790M
      mutant in NCI-H1975 cells, through an autophagic degradation by interacting with
      P62. This study potentially offers an innovative therapeutic avenue for the NSCLC
      with L858R/T790M-mutated EGFR.

PMID- 30237566
TI  - Diet induced changes in the microbiota and cell composition of rabbit gut
      associated lymphoid tissue (GALT).
AB  - The gut associated lymphoid tissue (GALT) is the largest immune organ of the
      body. Although the gut transient and mucosa-associated microbiota have been
      largely studied, the microbiota that colonizes the GALT has received less
      attention. The gut microbiome plays an important role in competitive exclusion of
      pathogens and in development and maturation of immunity. Diet is a key factor
      affecting the microbiota composition in the digestive tract. To investigate the
      relation between diet, microbiota and GALT, microbial and cell composition of
      vermiform appendix (VA) and sacculus rotundus (SR) were studied in two groups of
      New Zealand white rabbits on different diets. Diet shifted the lymphoid tissue
      microbiota affecting the presence and/or absence of certain taxa and their
      abundances. Immunohistochemistry revealed that a higher fibre content diet
      resulted in M cell hyperplasia and an increase of recently recruited macrophages,
      whereas T-cell levels remained unaltered in animals on both high fibre and
      standard diets. These findings indicate that diet has an impact on the microbiota
      and cell composition of the GALT, which could act as an important microbial
      recognition site where interactions with beneficial bacteria can take place
      favouring microbiota replacement after digestive dysregulations.

PMID- 30237567
TI  - Identification of depression subtypes and relevant brain regions using a data
      driven approach.
AB  - It is well known that depressive disorder is heterogeneous, yet little is known
      about its neurophysiological subtypes. In the present study, we identified
      neurophysiological subtypes of depression related to specific neural substrates.
      We performed cluster analysis for 134 subjects (67 depressive subjects and 67
      controls) using a high-dimensional dataset consisting of resting state functional
      connectivity measured by functional MRI, clinical questionnaire scores, and
      various biomarkers. Applying a newly developed, multiple co-clustering method to
      this dataset, we identified three subtypes of depression that are characterized
      by functional connectivity between the right Angular Gyrus (AG) and other brain
      areas in default mode networks, and Child Abuse Trauma Scale (CATS) scores. These
      subtypes are also related to Selective Serotonin-Reuptake Inhibitor (SSRI)
      treatment outcomes, which implies that we may be able to predict effectiveness of
      treatment based on AG-related functional connectivity and CATS.

PMID- 30237569
TI  - Sound transmission in a bamboo forest and its implications for information
      transfer in giant panda (Ailuropoda melanoleuca) bleats.
AB  - Although mammal vocalisations signal attributes about the caller that are
      important in a range of contexts, relatively few studies have investigated the
      transmission of specific types of information encoded in mammal calls. In this
      study we broadcast and re-recorded giant panda bleats in a bamboo plantation, to
      assess the stability of individuality and sex differences in these calls over
      distance, and determine how the acoustic structure of giant panda bleats degrades
      in this species' typical environment. Our results indicate that vocal recognition
      of the caller's identity and sex is not likely to be possible when the distance
      between the vocaliser and receiver exceeds 20 m and 10 m, respectively. Further
      analysis revealed that the F0 contour of bleats was subject to high structural
      degradation as it propagated through the bamboo canopy, making the measurement of
      mean F0 and F0 modulation characteristics highly unreliable at distances
      exceeding 10 m. The most stable acoustic features of bleats in the bamboo forest
      environment (lowest % variation) were the upper formants and overall formant
      spacing. The analysis of amplitude attenuation revealed that the fifth and sixth
      formant are more prone to decay than the other frequency components of bleats,
      however, the fifth formant still remained the most prominent and persistent
      frequency component over distance. Paired with previous studies, these results
      show that giant panda bleats have the potential to signal the caller's identity
      at distances of up to 20 m and reliably transmit sex differences up to 10 m from
      the caller, and suggest that information encoded by F0 modulation in bleats could
      only be functionally relevant during close-range interactions in this species'
      natural environment.

PMID- 30237568
TI  - Sex differences in the contribution of blood pressure to acute changes in aortic
      augmentation index.
AB  - Augmentation index (AIx), derived from aortic pulse waveform, is related to
      arterial stiffness and increased cardiac workload. Sex differences were observed
      in the relationship between blood pressure (BP) and AIx at rest. In addition,
      positive correlation between BP and AIx in men during a pressor stimulus was
      observed previously. However, whether BP is important to acute changes of AIx
      also in women is yet to be investigated. Therefore, we sought to investigate
      whether there are sex differences on the relationship between BP and AIx. In all,
      16 men (age 27 +/- 5 yr; height 176 +/- 1 cm; weight 77 +/- 7 kg; mean +/- SD)
      and 13 women (age 26 +/- 5 yr; height 164 +/- 0.3 cm; weight 63 +/- 7 kg; mean +/
      SD) underwent 3 min of rest followed by 3 min of cold pressor test (CPT). Heart
      rate during CPT was similar to rest. CPT increased BP in both groups and the
      magnitude was similar between groups. AIx and left ventricle energy wasted (EW)
      increased (men Delta13 +/- 5% and women Delta17 +/- 3%; p > 0.05 for group; men
      Delta580 +/- 242 dynes cm-2 s-1 and women Delta618 +/- 123 dynes cm-2 s-1; p >
      0.05 for group) similarly in men and women during CPT. A positive Pearson
      correlation was found between AIx and BP in men (systolic BP (SBP) r = 0.77, p =
      0.01; diastolic BP (DBP) r = 0.79, p = 0.01 and mean arterial pressure (MAP) r =
      0.83, p < 0.01), however no correlation was seen in women (SBP r = 0.04, p =
      0.89; DBP r = 0.24, p = 0.44 and MAP r = 0.23, p = 0.44). The contribution of BP
      to acute changes in AIx at higher levels of BP is different between men and
      women.

PMID- 30237570
TI  - Neurosteroid replacement therapy using the allopregnanolone-analogue ganaxolone
      following preterm birth in male guinea pigs.
AB  - BACKGROUND: Children born preterm, especially boys, are at increased risk of
      developing attention deficit hyperactivity disorder (ADHD) and learning
      difficulties. We propose that neurosteroid-replacement therapy with ganaxolone
      (GNX) following preterm birth may mitigate preterm-associated neurodevelopmental
      impairment. METHODS: Time-mated sows were delivered preterm (d62) or at term
      (d69). Male preterm pups were randomized to ganaxolone (Prem-GNX; 2.5 mg/kg
      subcutaneously twice daily until term equivalence), or preterm control (Prem
      CON). Surviving male juvenile pups underwent behavioural testing at d25-corrected
      postnatal age (CPNA). Brain tissue was collected at CPNA28 and mature myelinating
      oligodendrocytes of the hippocampus and subcortical white matter were quantified
      by immunostaining of myelin basic protein (MBP). RESULTS: Ganaxolone treatment
      returned the hyperactive behavioural phenotype of preterm-born juvenile males to
      a term-born phenotype. Deficits in MBP immunostaining of the preterm hippocampus
      and subcortical white matter were also ameliorated in animals receiving
      ganaxolone. However, during the treatment period weight gain was poor, and pups
      were sedated, ultimately increasing the neonatal mortality rate. CONCLUSION:
      Ganaxolone improved neurobehavioural outcomes in males suggesting that neonatal
      treatment may be an option for reducing preterm-associated neurodevelopmental
      impairment. However, dosing studies are required to reduce the burden of unwanted
      side effects.

PMID- 30237571
TI  - Perinatal nutrition impacts on the functional development of the visual tract in
      infants.
AB  - BACKGROUND AND OBJECTIVE: We investigated the associations of maternal diet and
      serum fatty acids during pregnancy and in early infancy on infantile
      neurodevelopment. METHODS: Pattern-reversal visual evoked potentials (pVEP) as
      depictors of central nervous system maturation were recorded from 56 children
      when they were 2 years old. Maternal nutrient intakes were calculated from food
      diaries and fish consumption from questionnaires collected during pregnancy.
      Serum phospholipid fatty acids were determined by gas chromatography in late
      pregnancy and from infants at 1 month of age. RESULTS: The children of the women
      who consumed fish three or more times per week during the last trimester of
      pregnancy had a higher pVEP component P100 amplitude for 60' (mean 23.4, SD 8.1)
      and 30' (mean 20.4, SD 6.7) of arcminute check sizes compared to those who
      consumed fish 0-2 times per week (mean 15.0, SD 4.8, p = 0.023, adjusted for
      birth weight and gender p = 0.058 and mean 13.4, SD 2.0, respectively, p = 0.028,
      adjusted p = 0.072). Maternal and child serum phospholipid fatty acids correlated
      with child pVEP measurements. CONCLUSION: The results of this small-scale study
      suggest that fish consumption during pregnancy and perinatal serum fatty acid
      status may associate with neurodevelopment within visual system during infancy.

PMID- 30237573
TI  - Kinetics of the invasion and egress processes of Babesia divergens, observed by
      time-lapse video microscopy.
AB  - Based on confocal fluorescence and bright field video microscopy, we present
      detailed observations on the processes of invasion and egress of erythrocytes by
      the apicomplexan parasite Babesia divergens. Time-lapse images reveal numerous
      unexpected findings associated with the dynamics of B. divergens and its ability
      to manipulate the erythrocyte during both processes in its asexual cycle under in
      vitro conditions. Despite the speed at which these processes occur and the small
      size of the parasite, we capture infective merozoites moving vigorously and
      causing striking deformations in the erythrocyte's plasma membrane during an
      active invasion. We also observed intraerythrocytic dynamic stages as paired
      pyriforms, double paired pyriforms, tetrads, unattached pyriform sister cells and
      multiple parasite stages resulting in the release of large numbers of merozoites
      over a short period. Of considerable interest is that time-lapse images reveal a
      novel mechanism of egress used by B. divergens to exit the human erythrocyte. The
      release occurs when B. divergens parasites establish contacts with the plasma
      membrane of the erythrocyte from within, before exiting the cell. Visualization
      and analysis of the images enabled us to obtain useful information and broaden
      our knowledge of complex and crucial events involved with parasitisation of human
      erythrocytes by B. divergens.

PMID- 30237572
TI  - The impact of fluid balance on outcomes in critically ill near-term/term
      neonates: a report from the AWAKEN study group.
AB  - BACKGROUND: In sick neonates admitted to the NICU, improper fluid balance can
      lead to fluid overload. We report the impact of fluid balance in the first
      postnatal week on outcomes in critically ill near-term/term neonates. METHODS:
      This analysis includes infants >=36 weeks gestational age from the Assessment of
      Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645).
      Fluid balance: percent weight change from birthweight. PRIMARY OUTCOME:
      mechanical ventilation (MV) on postnatal day 7. RESULTS: The median peak fluid
      balance was 1.0% (IQR: -0.5, 4.6) and occurred on postnatal day 3 (IQR: 1, 5).
      Nine percent required MV at postnatal day 7. Multivariable models showed the peak
      fluid balance (aOR 1.12, 95%CI 1.08-1.17), lowest fluid balance in 1st postnatal
      week (aOR 1.14, 95%CI 1.07-1.22), fluid balance on postnatal day 7 (aOR 1.12,
      95%CI 1.07-1.17), and negative fluid balance at postnatal day 7 (aOR 0.3, 95%CI
      0.16-0.67) were independently associated with MV on postnatal day 7. CONCLUSIONS:
      We describe the impact of fluid balance in critically ill near-term/term neonates
      over the first postnatal week. Higher peak fluid balance during the first
      postnatal week and higher fluid balance on postnatal day 7 were independently
      associated with MV at postnatal day 7.

PMID- 30237574
TI  - Correction: The effect of NOTCH3 pathogenic variant position on CADASIL disease
      severity: NOTCH3 EGFr 1-6 pathogenic variant are associated with a more severe
      phenotype and lower survival compared with EGFr 7-34 pathogenic variant.
AB  - This Article was originally published under Nature Research's License to Publish,
      but has now been made available under a [CC BY 4.0] license. The PDF and HTML
      versions of the Article have been modified accordingly.

PMID- 30237575
TI  - Factors influencing NCGENES research participants' requests for non-medically
      actionable secondary findings.
AB  - PURPOSE: Genomic sequencing can reveal variants with limited to no medical
      actionability. Previous research has assessed individuals' intentions to learn
      this information, but few report the decisions they made and why. METHODS: The
      North Carolina Clinical Genomic Evaluation by Next Generation Exome Sequencing
      (NCGENES) project evaluated adult patients randomized to learn up to six types of
      non-medically actionable secondary findings (NMASF). We previously found that
      most participants intended to request NMASF and intentions were strongly
      predicted by anticipated regret. Here we examine discrepancies between intentions
      and decisions to request NMASF, hypothesizing that anticipated regret would
      predict requests but that this association would be mediated by participants'
      intentions. RESULTS: Of the 76% who expressed intentions to learn results, only
      42% made one or more requests. Overall, only 32% of the 155 eligible participants
      requested NMASF. Analyses support a plausible causal link between anticipated
      regret, intentions, and requests. CONCLUSIONS: The discordance between
      participants' expressed intentions and their actions provides insight into
      factors that influence patients' preferences for genomic information that has
      little to no actionability. These findings have implications for the timing and
      methods of eliciting preferences for NMASF and suggest that decisions to learn
      this information have cognitive and emotional components.

PMID- 30237577
TI  - Stable isotope measurements show increases in corn water use efficiency under
      deficit irrigation.
AB  - Deficit irrigation has usually improved crop water use efficiency (WUE), but
      there are still gaps in our understanding of the mechanisms. Four irrigation
      treatments were a conventional furrow irrigation (CFI), border irrigation (BI),
      alternate furrow irrigation (AFI), and an AFI(M/2) (the amount of irrigation was
      50% of the AFI). The volume of irrigation water applied were nearly the same for
      CFI, BI, and AFI. The isotope (delta18O and deltaD) method was used to quantify
      corn root water uptake (RWU) during 2013-2014. Compared to CFI and BI, corn yield
      and WUE were 17.0-30.2% and 13.3-33.8% higher in AFI, respectively. No
      significant yield reduction were observed between AFI and AFI(M/2). Corn RWU was
      more from deeper soil with increasing growth stage for AFI(M/2), AFI, and CFI,
      but from shallower depth for BI. The depth for RWU varied in the order of
      AFI(M/2)  > AFI > CFI > BI. The maximum root density was in the depth of 40-80 cm
      at the growing stage in AFI, and 4-26% more water was extracted from the wetter
      and deeper root zones. The WUE increased under deficit irrigation, and stimulated
      the root growth with attendant decreases in water loss to deep percolation.

PMID- 30237578
TI  - Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative
      stress and inflammatory responses via blocking of STAT3 activity.
AB  - Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have
      broader functions including potent antioxidant, anti-inflammatory and
      neuroprotective properties. Considerable researches have demonstrated that AXT
      shows preventive and therapeutic properties against for Diabetes, Osteoarthritis
      and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease
      has not yet been reported. In this study, we investigated effects of AXT on
      ethanol-induced liver injury in chronic plus binge alcohol feeding model. The
      hepatic steatosis and inflammation induced by ethanol administration were
      alleviated by AXT. Serum levels of aspartate transaminase and alanine
      transaminase were decreased in the livers of AXT administrated group. The ethanol
      induced expression of cytochrome P450 2E1 (CYP2E1), pro-inflammatory proteins,
      cytokines, chemokines and reactive oxygen species (ROS) levels were also reduced
      in the livers of AXT administrated group. Moreover, ethanol-induced infiltration
      of neutrophils was decreased in the livers of AXT administrated group. Docking
      model and pull-down assay showed that AXT directly binds to the DNA binding site
      of STAT3. Moreover, AXT decreased STAT3 phosphorylation in the liver of AXT
      administration group. Therefore, these results suggest that AXT could prevent
      ethanol-induced hepatic injury via inhibition of oxidant and inflammatory
      responses via blocking of STAT3 activity.

PMID- 30237579
TI  - Fibulin-2 is required for basement membrane integrity of mammary epithelium.
AB  - Fibulin-2 (FBLN2) is a secreted extracellular matrix glycoprotein which has been
      associated with tissue development and remodelling. In the mouse mammary gland,
      FBLN2 can be detected during ductal morphogenesis in cap cells and myoepithelial
      cells at puberty and early pregnancy, respectively. In an attempt to assign its
      function, we knocked down Fbln2 in the mouse mammary epithelial cell line EpH4.
      FBLN2 reduction led to an increase in the size of spheroidal structures when
      compared to scrambled control shRNA-transduced cells plated on Matrigel matrix.
      This phenotype was associated with a disruption of the collagen IV sheath around
      the epithelial spheroids and downregulation of integrin beta1, suggesting a role
      for FBLN2 in stabilizing the basement membrane (BM). In contrast to mice, in
      normal adult human breast tissue, FBLN2 was detected in ductal stroma, and in the
      interlobular stroma, but was not detectable within the lobular regions. In tissue
      sections of 65 breast cancers FBLN2 staining was lost around malignant cells with
      retained staining in the neighbouring histologically normal tissue margins. These
      results are consistent with a role of FBLN2 in mammary epithelial BM stability,
      and that its down-regulation in breast cancer is associated with loss of the BM
      and early invasion.

PMID- 30237581
TI  - Genetic markers in methotrexate treatments.
AB  - Methotrexate (MTX), a structural analog of folic acid, is widely employed in the
      treatment of different cancers and autoimmune diseases. Despite the successful
      results observed, the main disadvantage lies in interpatient variability in the
      pharmacokinetic and pharmacodynamic parameters. In particular, adverse events and
      toxicities induced by MTX are a matter of concern and can be the cause of dose
      reduction or treatment discontinuation. Among the different approaches to reduce
      MTX therapeutic limitations, pharmacogenomics contributes by considering the
      effect of inherited genetic differences on those parameters. This review provides
      an update on MTX pharmacogenomics. It reports the contribution of main gene
      polymorphisms involved in the influx, efflux, cellular effect, and elimination on
      MTX toxicity and efficacy, on all the diseases treated with this drug. From the
      analysis of the data presented in this review, we concluded that only gene
      polymorphisms MTHFR rs1801133, SLC19A1 rs1051266, and TYMS rs34743033 could
      influence clinical decision-making.

PMID- 30237580
TI  - Protease-activated receptor 2 signaling modulates susceptibility of colonic
      epithelium to injury through stabilization of YAP in vivo.
AB  - Hippo signaling plays critical roles in intestinal regeneration. However, the
      mechanisms which regulate its activity in vivo are largely unknown. We
      hypothesize that protease-activated receptor 2 (PAR2) signaling, which could be
      activated by trypsin, might affect YAP activity in the setting of tissue damage
      and regeneration. It is found that knockout of PAR2 severely aggravates the
      mucosal damage induced by dextran sodium sulfate (DSS) in mouse, which correlated
      with notable repression of YAP protein in colonic epithelial cells. Although the
      cytokine expression is reduced, the damage of colonic crypt is more severe after
      DSS-induced colitis in PAR2-/- mouse. In vitro, PAR2 activation causes the
      accumulation of YAP, while knockdown of PAR2 with shRNA dramatically represses
      the expression of YAP protein in different intestinal epithelial cell lines.
      Moreover, forced expression of YAP significantly reduces the production of
      reactive oxygen species (ROS) and the sensitivity to nitric oxide-induced
      apoptosis in PAR2-deficient condition. Further studies show that PAR2 signaling
      stabilizes YAP protein but independent of Lats. Nevertheless PAR2 activation
      increased the binding of YAP with protein phosphatase PP1. Inhibition of PP1 with
      specific siRNA blocked PAR2-induced dephosphorylation of YAP. Taken together,
      PAR2 signaling might modulate susceptibility of colonic epithelium to injury
      through stabilization of YAP.

PMID- 30237576
TI  - Autozygome and high throughput confirmation of disease genes candidacy.
AB  - PURPOSE: Establishing links between Mendelian phenotypes and genes enables the
      proper interpretation of variants therein. Autozygome, a rich source of
      homozygous variants, has been successfully utilized for the high throughput
      identification of novel autosomal recessive disease genes. Here, we highlight the
      utility of the autozygome for the high throughput confirmation of previously
      published tentative links to diseases. METHODS: Autozygome and exome analysis of
      patients with suspected Mendelian phenotypes. All variants were classified
      according to the American College of Medical Genetics and Genomics guidelines.
      RESULTS: We highlight 30 published candidate genes (ACTL6B, ADAM22, AGTPBP1, APC,
      C12orf4, C3orf17 (NEPRO), CENPF, CNPY3, COL27A1, DMBX1, FUT8, GOLGA2, KIAA0556,
      LENG8, MCIDAS, MTMR9, MYH11, QRSL1, RUBCN, SLC25A42, SLC9A1, TBXT, TFG, THUMPD1,
      TRAF3IP2, UFC1, UFM1, WDR81, XRCC2, ZAK) in which we identified homozygous likely
      deleterious variants in patients with compatible phenotypes. We also identified
      homozygous likely deleterious variants in 18 published candidate genes (ABCA2,
      ARL6IP1, ATP8A2, CDK9, CNKSR1, DGAT1, DMXL2, GEMIN4, HCN2, HCRT, MYO9A, PARS2,
      PLOD3, PREPL, SCLT1, STX3, TXNRD2, WIPI2) although the associated phenotypes are
      sufficiently different from the original reports that they represent phenotypic
      expansion or potentially distinct allelic disorders. CONCLUSIONS: Our results
      should facilitate the timely relabeling of these candidate disease genes in
      relevant databases to improve the yield of clinical genomic sequencing.

PMID- 30237582
TI  - HLA-C*12:02 is strongly associated with Xuesaitong-induced cutaneous adverse drug
      reactions.
AB  - Xuesaitong (XST) is mainly used to treat cardiovascular and cerebrovascular
      diseases, sometimes causing cutaneous adverse drug reactions (cADRs) with unknown
      mechanisms of pathogenicity or risk factors. We aimed to verify whether human
      leukocyte antigen (HLA) alleles are associated with XST-related cADRs in Han
      Chinese population. We carried out an association study including 12 subjects
      with XST-induced cADRs, 283 controls, and 28 XST-tolerant subjects. Five out of
      12 patients with XST-induced cADRs carried HLA-C*12:02, and all of them received
      XST via intravenous drip. The carrier frequency of HLA-C*12:02 was significantly
      high compare to that of the control population (Pc = 4.4 * 10-4, odds ratio (OR)
      = 21.75, 95% CI = 5.78-81.88). Compared with that of the XST-tolerant group, the
      patients who received XST through intravenous drip presented a higher OR of cADRs
      (Pc = 0.011, OR = 27.00, 95% CI = 2.58-282.98). The results suggest that HLA
      C*12:02 is a potentially predictive marker of XST-induced cADRs in Han Chinese,
      especially when XST is administered via intravenous drip.

PMID- 30237583
TI  - An exploratory study by DMET array identifies a germline signature associated
      with imatinib response in gastrointestinal stromal tumor.
AB  - Imatinib represents the standard therapy for gastrointestinal stromal tumor
      (GIST) patients with metastatic/unresectable disease. Despite  the excellent
      results achieved with its introduction, the majority of patients quite invariably
      experience disease progression. The aim of this study was to understand the
      contribution of germline DNA polymorphisms in discriminating between imatinib
      clinical response [evaluated as progression free survival (PFS)] and toxicity. In
      particular, a discovery cohort (34 GIST with a KIT exon 11 primary mutation, and
      no toxicity) was analyzed through DMET array that interrogates 1936 variants in
      231 genes of the ADME process. We further confirmed the genotype of selected
      variants in an extended cohort of 49 patients (the original cohort and 15 new
      cases, all with exon 11 primary mutation), identifying 6 SNPs- ABCB4 rs1202283,
      ABCC2 rs2273697, ABCG1 rs1541290, CYP11B1 rs7003319, CYP7B1 rs6987861, and NQO1
      rs10517-significantly associated with response to imatinib. Three SNPs, ABCB4
      rs1202283, ABCC2 rs2273697, and NQO1 rs10517, which had a significant association
      after adjusted multivariate analysis, were included in a genetic prediction
      model. We confirmed that these SNPs could stratify the cohort of 49 patients
      according to the risk of developing progression under imatinib treatment. In
      conclusion, we identified a genetic signature of response to imatinib therapy in
      GIST patients able to stratify patients at low and high risk to progress,
      according to their genotype.

PMID- 30237585
TI  - Dystonia.

PMID- 30237586
TI  - Draining phenomenon in closed narrow tubes pierced at the top: an experimental
      and theoretical analysis.
AB  - The phenomenon of draining, although ubiquitous in nature, has received scant
      attention especially in the meso-scale. We observe that closed top tubes drain by
      the inception of an axisymmetric 'Taylor finger' while a minute pierce of the top
      closure results in an altogether different physics with air entry from the top
      pushing the liquid out. Again, a coupled mechanism comprising full bore followed
      by film draining is observed for "too small" a top pierce at "high enough" Eotvos
      number. Top pierce initiates draining in dimensions which would not drain
      otherwise and finger entry hastens the process of draining. The myriad of
      phenomena thus exhibited is depicted as phase diagrams in vertical and inclined
      conduits. A mechanistic model has been proposed to predict draining and the onset
      of finger entry in vertical tubes.

PMID- 30237587
TI  - Adaptive Gaze Strategies to Reduce Environmental Uncertainty During a Sequential
      Visuomotor Behaviour.
AB  - People must decide where, when, and for how long to allocate gaze to perform
      different motor behaviours. However, the factors guiding gaze during these
      ongoing, natural behaviours are poorly understood. Gaze shifts help acquire
      information, suggesting that people should direct gaze to locations where
      environmental details most relevant to the task are uncertain. To explore this,
      human subjects stepped on a series of targets as they walked. We used different
      levels of target uncertainty, and through instruction, altered the importance of
      (or subjective value assigned to) foot-placement accuracy. Gaze time on targets
      increased with greater target uncertainty when precise foot placement was more
      important, and these longer gaze times associated with reduced foot-placement
      error. Gaze times as well as the gaze shifts to and from targets relative to
      stepping differed depending on the target's position in the sequence and
      uncertainty level. Overall, we show that gaze is allocated to reduce uncertainty
      about target locations, and this depends on the value of this information gain
      for successful task performance. Furthermore, we show that the spatial-temporal
      pattern of gaze to resolve uncertainty changes with the evolution of the motor
      behaviour, indicating a flexible strategy to plan and control movement.

PMID- 30237584
TI  - Genome-wide association analysis of common genetic variants of resistant
      hypertension.
AB  - Resistant hypertension (RHTN), defined as uncontrolled blood pressure (BP) >=
      140/90 using three or more drugs or controlled BP (<140/90) using four or more
      drugs, is associated with adverse outcomes, including decline in kidney function.
      We conducted a genome-wide association analysis in 1194 White and Hispanic
      participants with hypertension and coronary artery disease from the INternational
      VErapamil-SR Trandolapril STudy-GENEtic Substudy (INVEST-GENES). Top variants
      associated with RHTN at p < 10-4 were tested for replication in 585 White and
      Hispanic participants with hypertension and subcortical strokes from the
      Secondary Prevention of Subcortical Strokes GENEtic Substudy (SPS3-GENES). A
      genetic risk score for RHTN was created by summing the risk alleles of replicated
      RHTN signals. rs11749255 in MSX2 was associated with RHTN in INVEST (odds ratio
      (OR) (95% CI) = 1.50 (1.2-1.8), p = 7.3 * 10-5) and replicated in SPS3 (OR = 2.0
      (1.4-2.8), p = 4.3 * 10-5), with genome-wide significance in meta-analysis (OR =
      1.60 (1.3-1.9), p = 3.8 * 10-8). Other replicated signals were in IFLTD1 and
      PTPRD. IFLTD1 rs6487504 was associated with RHTN in INVEST (OR = 1.90 (1.4-2.5),
      p = 1.1 * 10-5) and SPS3 (OR = 1.70 (1.2-2.5), p = 4 * 10-3). PTPRD rs324498, a
      previously reported RHTN signal, was among the top signals in INVEST (OR = 1.60
      (1.3-2.0), p = 3.4 * 10-5) and replicated in SPS3 (OR = 1.60 (1.1-2.4), one-sided
      p = 0.005). Participants with the highest number of risk alleles were at
      increased risk of RHTN compared to participants with a lower number (p-trend =
      1.8 * 10-15). Overall, we identified and replicated associations with RHTN in the
      MSX2, IFLTD1, and PTPRD regions, and combined these associations to create a
      genetic risk score.

PMID- 30237588
TI  - Changes in sex ratio at birth among immigrant groups in Sweden.
AB  - What happens when citizens from societies with strong son preference culture
      migrate to countries in which preference for having a child of each sex prevails?
      Using data from Swedish population registers, we investigate the sex ratio at
      birth by parity and the sex composition of previous children in Sweden. Our
      results showed that women with Chinese, Korean, and Indian background had a
      substantially elevated sex ratio at the third parity if previous children were
      both girls. Strikingly, this skewed ratio became less pronounced after 2000,
      suggesting a shift for a more neutral sex preference for children among these
      groups in the new century.

PMID- 30237589
TI  - Physiological and anatomical changes of pregnancy: Implications for anaesthesia.
AB  - During pregnancy, the body goes through various anatomical and physiological
      changes to provide suitable environment for foetal development, to cater to the
      increased metabolic demands and to prepare for the childbirth. These changes have
      notable anaesthetic implications in determining the optimal anaesthetic
      technique, while also keeping in mind the gestational age, type of procedure and
      any coexisting medical condition. It is important to note that these changes
      revert to baseline (pre-pregnancy) levels at different time intervals during the
      postpartum period which is important while managing postpartum patients. None of
      the anaesthetic agents are known teratogens; however, there is concern regarding
      the effects of some agents on the developing brain.

PMID- 30237591
TI  - Management of anaesthesia for elective, low-risk (Category 4) caesarean section.
AB  - An increasing number of caesarean sections are being performed for both elective
      as well as emergency cases. Category 4 caesarean section refers to a planned
      elective surgery after 39 weeks of gestation at a time suitable to the mother and
      the maternity team. For a safe conduct of anaesthesia, the updated obstetric
      anaesthesia guidelines recommend administration of neuraxial anaesthesia,
      whenever feasible. The management should include adequate postoperative pain
      relief, early ambulation, and thromboprophylaxis to ensure early recovery. This
      review will discuss the anaesthetic management including regional anaesthesia,
      general anaesthesia, and postoperative analgesia for elective, low-risk (Category
      4) caesarean section.

PMID- 30237590
TI  - Neuraxial techniques of labour analgesia.
AB  - In recent years, many neuraxial techniques have been introduced to initiate and
      maintain labour analgesia, with low-dose mixtures of local anaesthetics and
      opioids, which have improved the quality of analgesia and made it safer for both
      mother and neonate. An independent search of the databases of PubMed, Medline,
      and Cochrane controlled trial data was conducted by two researchers, and
      randomized controlled trials that compared different methods of neuraxial
      analgesia and the different techniques of maintaining labor analgesia were
      retrieved and analyzed. The advantages, disadvantages, and indications of each
      technique along with the doses of intrathecal and epidural drugs are discussed.
      The myths and controversies involving neuraxial labor analgesia and the current
      consensus on their effect on the maternal and foetal outcomes are also outlined.

PMID- 30237592
TI  - Hypertensive disorders in pregnancy.
AB  - Hypertensive disorders of pregnancy (HDP) remain among the most significant and
      intriguing unsolved problems in obstetrics. In India, the prevalence of HDP was
      7.8% with pre-eclampsia in 5.4% of the study population. The anaesthetic problems
      in HDP may be due to the effects on the cardiovascular, respiratory, neurologic,
      renal, haematologic, hepatic and uteroplacental systems. The basic management
      objectives should be facilitating the birth of an infant who subsequently thrives
      and completes restoration of health to the mother, or the termination of
      pregnancy with the least possible trauma to mother and foetus in severe pre
      eclampsia. This comprises obstetric management, adequate foetal surveillance,
      antihypertensive management, anticonvulsant therapy, safe analgesia for labour
      and management of anaesthesia for delivery.

PMID- 30237593
TI  - Neuraxial anaesthesia in parturient with cardiac disease.
AB  - Parturient with corrected or uncorrected cardiac problem may undergo neuraxial
      anaesthesia for several reasons and in different trimesters. The altered
      physiological state in a parturient is further deranged in the presence of a
      cardiovascular lesion, producing the added risk to the parturient undergoing a
      neuraxial block. A detailed evaluation, knowledge regarding cardiovascular
      disease state, more vigilant monitoring, and a team approach can lead to a
      successful outcome.

PMID- 30237595
TI  - Management of major obstetric haemorrhage.
AB  - One of the most important causes of maternal mortality is major obstetric
      haemorrhage. Major haemorrhage can occur in parturients either during the
      antepartum period, during delivery, or in the postpartum period. Early
      recognition and a multidisciplinary team approach in the management are the
      cornerstones of improving the outcome of such cases. The management consists of
      fluid resuscitation, administration of blood and blood products, conservative
      measures such as uterine cavity tamponade and sutures, and finally hysterectomy.
      Blood transfusion strategies have changed over the last decade with emphasis on
      use of fresh frozen plasma, platelets, and fibrinogen. Point-of-care testing for
      treating coagulopathies promptly and interventional radiological procedures have
      further revolutionized the management of such cases.

PMID- 30237594
TI  - Approach to failed spinal anaesthesia for caesarean section.
AB  - Failure of spinal anaesthesia for caesarean section may have deleterious
      consequences for the mother as well as the newborn baby. In this article, we
      discuss the mechanisms of failure of spinal anaesthesia as well as the approach
      to a failed block. We performed a literature search in Google Scholar, PubMed,
      and Cochrane databases for original and review articles concerning failed spinal
      anaesthesia and caesarean section. Strategies for a failed spinal anaesthetic
      include manoeuvers to salvage the block, repeating the block, epidural
      anaesthesia or a combined spinal-epidural (CSE) technique, or resorting to
      general anaesthesia. Factors influencing the choice of these alternative options
      are discussed. A "failed spinal algorithm" can guide the anaesthesiologist and
      help reduce morbidity and mortality.

PMID- 30237596
TI  - Anaesthetic management of obstetric emergencies.
AB  - Obstetric emergencies are a challenge both for the obstetrician and the
      anaesthesiologist. The incidence of caesarean sections as per the National Family
      Health Survey published in 2015-16 was 17.2%. In 7.6% of cases, the decision to
      conduct a caesarean section was taken after the onset of labour pains. Caesarean
      sections are classified depending on the urgency into four categories. The target
      decision to delivery interval for category 1 caesarean section is less than 30
      min. This is used as an audit tool for the efficiency of an obstetric service.
      The management of these emergencies involves a rapid assessment, with minimal
      investigations. Although general anaesthesia is considered to have higher
      morbidity and mortality, category 1 caesarean sections may still warrant this
      technique. Rapid sequence spinal anaesthesia is replacing general anaesthesia for
      many of the category 1 indications. In category 2 and 3 caesarean sections,
      spinal anaesthesia still remains the technique of choice. Failed intubation,
      failed neuraxial block, extensive neuraxial block, awareness under anaesthesia,
      thromboembolism, amniotic fluid embolism, haemorrhage and maternal collapse are
      some of the complications. Haemorrhage is said to be the leading cause of
      mortality worldwide.

PMID- 30237597
TI  - Anaesthesia for non-obstetric surgery in obstetric patients.
AB  - Anaesthesia for pregnant patients presenting for non-obstetric surgery needs a
      thorough understanding of the physiological changes and altered pharmacokinetics
      of pregnancy. Considering the effects of surgery and anaesthesia on the foetus,
      only essential and emergency surgeries are performed during pregnancy. Surgical
      procedures in second trimester have the advantage of better foetal outcome. The
      primary concerns of maternal and foetal safety are achieved by a focused
      multidisciplinary team-based approach with respect to the surgical condition.
      Meticulous attention to preoperative patient counselling, airway management,
      haemodynamic stability, and thromboprophylaxis are the key factors in anaesthetic
      management. Choice of anaesthesia or anaesthetic drugs has minimal impact on the
      foetus provided utero-placental perfusion and uterine relaxation are maintained.
      Foetal monitoring when feasible and when done by a trained person enables to
      diagnose and treat the factors responsible for foetal heart rate variability.
      Anaesthetic technique needs to be modified according to the type of surgery.

PMID- 30237600
TI  - Let's Give Our Best to the Children: The Pediatric Trauma Symposium.

PMID- 30237599
TI  - Critical care in obstetrics.
AB  - Pregnancy is a normal physiologic process with the potential for pathologic
      states. Pregnancy has several unique characteristics including an utero-placental
      interface, a physiologic stress that can cause pathologic states to develop, and
      a maternal-foetal interface that can affect two lives simultaneously or in
      isolation. Critical illness in pregnant women may result from deteriorating
      preexisting conditions, diseases that are co-incidental to pregnancy, or
      pregnancy-specific conditions. Successful maternal and neonatal outcomes for
      parturients admitted to a maternal critical care facility are largely dependent
      on a multidisciplinary input to medical or surgical condition from critical care
      physicians, obstetric anaesthesiologists, obstetricians, obstetric physicians,
      foetal medicine specialists, neonatologists, and concerned specialists. Pregnant
      women requiring maternal critical care unit admission are relatively low in
      developed nations and range from 0.9% to 1%; but in our country, the admission
      rates of critically ill parturients range from 3% to 8%. Two-thirds of pregnant
      women requiring critical care are often unanticipated at the time of conception.
      In this review, we will look at critical illnesses in pregnant women with a
      specific focus on pregnancy-induced illnesses.

PMID- 30237598
TI  - Foetal surgery: Anaesthetic implications and strategic management.
AB  - Intrauterine surgery is being performed with increasing frequency. Correction of
      foetal anomalies in utero can result in normal growth of foetus and a healthier
      baby at delivery. Intrauterine surgery can also improve the survival of babies
      who would have otherwise died at delivery, or in the neonatal period. There are
      three commonly used approaches to correct foetal anomalies: open surgery, where
      the foetus is exposed through hysterotomy; percutaneous approach, where needle or
      foetoscope is inserted through the abdominal wall and the uterine wall; finally,
      ex utero intrapartum treatment (EXIT) surgery, where the intervention is
      performed on the baby before terminating the maternal umbilical support to the
      baby. Anaesthetic management of the mother and the foetus requires good
      understanding of maternal physiology, foetal physiology, and pharmacological and
      surgical implications to the foetus. Uterine relaxation is a critical requisite
      for open foetal procedures and EXIT procedures. General anaesthesia and/or
      regional anaesthesia can be used successfully depending on the nature of foetal
      intervention. Foetal surgery poses complications not only to the foetus but also
      to the mother. Therefore, the decision for undertaking foetal surgery should
      always consider the risk to the mother versus benefit to the foetus.

PMID- 30237601
TI  - Epidemiology of Pediatric Musculoskeletal Injuries and Their Pattern in a
      Tertiary Care Center of North India.
AB  - Background: Trauma is emerging as an epidemic and a leading cause of morbidity
      and mortality in children. Children <15 years of age comprise about 32.8% or
      about 1/3rd of the total Indian population. In India, up to one fourth of
      hospital admissions and approximately 15% of deaths in children are due to
      injury. This study presents the epidemiology, various causes and pattern of
      musculoskeletal injuries in pediatric population of North India. Materials and
      Methods: This is an observational, prospective hospital-based study conducted in
      a tertiary care center of North India for 6 months from July to December 2016.
      All pediatric patients in the age group 0-15 years who presented to the
      orthopedic emergency and out patient department with a history of trauma were
      included in the study. Results: Children aged 6-15 years (58%) suffered more
      injuries than children under 5 years of age (42%). Male pediatric population
      (58.5%) had more musculoskeletal injuries as compared to female pediatric
      population of the same age group (41.5%) in both the groups. Urban pediatric
      population (68.78%) suffered more injuries as compared to rural population of the
      same age group. Right extremities were more commonly involved in both the age
      groups. Upper limb injuries (50.59% in 0-5 years age group and 47.42% in 6- 15
      years age group) were most common followed by lower limb and pelvic injuries.
      Very few (2.9% in 0- 5 years age group and 4.8% in 6-15 years age group) patients
      sustained isolated spinal injuries. Out of the 3712 patients 59.40% of patients
      had a history of fall, followed by road traffic accident related injuries (32%).
      The most common injuries were superficial injuries i.e., abrasions and bruises.
      The second most common injury was cut or open wounds mostly seen on hand, forearm
      and legs. Conclusion: The high incidence of pediatric trauma on roads and falls
      indicates the need for more supervision during playing and identification of
      specific risk factors for these injuries in our setting. Injuries in pediatric
      age group by and large is a preventable condition. Therefore, injury prevention
      in children should be a priority.

PMID- 30237603
TI  - Growth Plate Injuries of the Lower Extremity: Case Examples and Lessons Learned.
AB  - Background: The presence of growth plates at the ends of long bones makes
      fracture management in children unique in terms of the potential risk of
      developing angular deformities and growth arrest. Materials and Methods: We
      discuss three distinct cases depicting various aspects of physeal injury of the
      lower extremity in children. Results: The case illustrations chosen represent
      distinct body regions and different physeal injuries: Salter-Harris II fracture
      of the distal femur, Salter-Harris VI perichondrial injury of the medial aspect
      of the knee region, and Salter-Harris III fracture of the distal tibia. The
      clinical presentation, pertinent history and physical findings, imaging studies,
      management, and subsequent course are presented. Conclusions: Growth plate
      injuries of the lower extremity require a high index of suspicion and close
      monitoring during skeletal growth. Early recognition and proper management of
      these injuries can minimize long term morbidity. The treatment plan should be
      individualized after a comprehensive analysis of the injury pattern in each
      patient. Establishing a long term treatment plan and discussing the prognosis of
      these injuries with the child's caretakers is imperative.

PMID- 30237604
TI  - Optimizing Management of Open Fractures in Children.
AB  - Open fractures in children differ from adults owing to their better healing
      potential. Management strategies for open fracture in children are changing with
      improvement in our understanding of soft-tissue reconstruction and fracture
      fixation. A literature review was performed for articles covering management of
      open fractures in children. The cornerstones of management include prevention of
      infection, debridement, and skeletal stabilization with soft-tissue coverage. The
      injury should be categorized according to the established trauma classification
      systems. Timely administration of appropriate antibiotics is important for
      preventing infections. Soft-tissue management includes copious irrigation and
      debridement of the wound. Fractures can be stabilized by a variety of
      nonoperative and operative means, taking into consideration the special needs of
      the growing skeleton and the role of a thick and active periosteum in the healing
      of fractures. The soft-tissue coverage required depends on the grade of injury.

PMID- 30237605
TI  - Foreign Body-Related Extremity Trauma in Children: A Single-Center Experience.
AB  - The extremity foreign body in a child has propensity of getting missed or
      mistaken diagnosis. We report our experience of extremity foreign body trauma in
      order to increase awareness of this disease entity. The retrospective series of
      24 retained foreign bodies was based on a 10-year chart review of emergency data
      (ICD code Z18). Patients with both upper and lower limb affections were included.
      Patients with ocular, otolaryngeal, tracheobronchial, gastrointestinal, and axial
      foreign bodies were excluded from the study. Male predominance (M:F = 20:4),
      young patient age (mean 6.8 years), variable lag period for consultation (range 3
      h-8 years), and majority lower limb affection (58%; foot [7; 29%] and knee [5;
      20.8%]) were some characteristics of extremity foreign bodies trauma. The foreign
      bodies reported were metallic needle (7; 29%), rubber band (3; 12.5%), pellets
      (3; 12.5%), bangle glass (2; 8%), glass pieces (2; 8%) "dhaga," wooden twig,
      wooden thorn, ceramic earthen pot pieces, stapler pin, broomstick, and cracker
      piece in one case each (1; 4%). Postremoval, the wound healing was uneventful in
      all patients. Foreign body-related extremity trauma in children is a rare event.
      It has its own set of characteristics and differential diagnosis. Familiarity
      with the regional practices and customs is must to establish the
      circumstances/nature of the foreign body injury. The foreign body should
      preferably be removed in a well-equipped setting.

PMID- 30237602
TI  - Management of Orthopaedic Injuries in Multiply Injured Child.
AB  - Multiply injured child is a unique challenge to the medical communities
      worldwide. It is a leading cause of preventable mortality and morbidity in
      children. Common skeletal injuries include closed or open fractures of tibia and
      femur and pelvic injuries. Initial management focuses on saving life and then
      saving limb as per pediatric advanced life support and advanced trauma life
      support. Orthopedic management of open fracture includes splinting the limb,
      administration of prophylactic antibiotic, and surgical debridement of the wound
      when safe. However, gross contamination, compartment syndrome, and vascular
      injuries demand urgent attention.

PMID- 30237607
TI  - Femoral Neck Fractures in Children: A Review.
AB  - Paediatric femoral neck fractures are uncommon injuries and are usually caused by
      high-energy trauma. Low-energy trauma can result in pathologic neck fractures and
      stress fractures of the neck, due to repetitive activity. Surgical options can
      vary based on age, Delbet classification and displacement of the fracture.
      Treatment for displaced fractures is by closed or open reduction and
      smooth/cancellous screw fixation. Compression screw and side plate fixation is
      indicated for basal fractures. Fixation should be supplemented by spica cast
      immobilization in younger children. The high rate of complications occurs due to
      the vascular anatomy of the hip and proximal femur. Avascular necrosis, coxa
      vara, premature physeal closure, and nonunion are the most common and these often
      result in poor outcome.

PMID- 30237608
TI  - Titanium Elastic Nailing with Temporary External Fixator versus Bridge Plating in
      Comminuted Pediatric Femoral Shaft Fractures: A Comparative Study.
AB  - Background: High-velocity trauma, associated injuries, risk of iatrogenic
      devascularization of fragments and need for maintaining alignment upto union make
      comminuted fracture in pediatric femur a formidable fracture to treat. This
      comparative study was conducted to evaluate the outcomes of two modes of
      management in such cases: titanium elastic nailing supplemented with external
      fixator and submuscular bridge plating (BP). Materials and Methods: Thirty eight
      children (aged 6-12 years) with comminuted fracture shaft femur who were
      randomized into two groups underwent systematic evaluation. One group was
      operated with titanium nailing with temporary external stabilization by fixators
      (titanium nailing with external [TNE] group) for 4 weeks. The other underwent
      submuscular BP with locked plates (BP group). Clinical and radiological outcomes,
      operative time, blood loss, radiation exposure, difficulties in removal and
      complications were evaluated. Results: Both groups achieved union (10.7 +/- 1.9
      weeks BP, 11 +/- 1.6 weeks TNE), satisfactory knee flexion (138.2 +/- 6.4 degrees
      BP, 136 +/- 7.3 degrees  TNE), and painless weight bearing (7.3 +/- 0.9 weeks
      vs. 7.3 +/- 1.4 weeks) in acceptable alignment. Functional outcomes were
      excellent in majority of both BP (15 of 19) and nail external fixator groups (15
      of 18). Operating time and radiation exposure (69.5 +/- 14.5 s vs. 50.9 +/- 12.9
      s) were more in TNE than in BP (P < 0.01). However, implant removal was more
      difficult in BP (56.4 +/- 12.4 min in BP vs. 30.1 +/- 8.8 min TNE). Pin-tract
      infections (n = 3) and hardware prominence (n = 2) in TNE group and deep
      infections (n = 2) in BP group were notable complications. Conclusion: Two groups
      were similar in radiological and functional outcomes. Inserting elastic nails and
      external fixator was a more exacting surgery, while removal was more difficult in
      BP group. Both techniques had acceptable success and complication rates.

PMID- 30237606
TI  - Cervical Spine Evaluation in Pediatric Trauma: A Review and an Update of Current
      Concepts.
AB  - The clinical presentation and diagnostic workup in pediatric cervical spine
      injuries (CSI) are different from adults owing to the unique anatomy and relative
      immaturity. The current article reviews the existing literature regarding the
      uniqueness of these injuries and discusses the current guidelines of radiological
      evaluation. A PubMed search was conducted using keywords "paediatric cervical
      spine injuries" or "paediatric cervical spine trauma." Six hundred and ninety two
      articles were available in total. Three hundred and forty three articles were
      considered for the review after eliminating unrelated and duplicate articles.
      Further screening was performed and 67 articles (original articles and review
      articles only) related to pediatric CSI were finally included. All articles were
      reviewed for details regarding epidemiology, injury patterns, anatomic
      considerations, clinical, and radiological evaluation protocols. CSIs are the
      most common level (60%-80%) for pediatric Spinal Injuries (SI). Children suffer
      from atlantoaxial injuries 2.5 times more often than adults. Children's unique
      anatomical features (large head size and highly flexible spine) predispose them
      to such a peculiar presentation. The role of National Emergency X-Ray Utilization
      Study, United State (NEXUS) and Canadian Cervical Spine Rule criteria in
      excluding pediatric cervical injury is questionable but cannot be ruled out
      completely. The minimum radiological examination includes 2- or 3-view cervical X
      rays (anteroposterior, lateral +/- open-mouth odontoid views). Additional
      radiological evaluations, including computerized tomography (CT) and magnetic
      resonance imaging (MRI) are obtained in situations of abnormal physical
      examination, abnormal X-rays, inability to obtain adequate X-rays, or to assess
      cord/soft-tissue status. The clinical criteria for cervical spine injury
      clearance can generally be applied to children older than 2 years of age.
      Nevertheless, adequate caution should be exercised before applying these rules in
      younger children. Initial radiographic investigation should be always adequate
      plain radiographs of cervical spine. CT and MRI scans should only be performed in
      an appropriate group of pediatric patients.

PMID- 30237610
TI  - Pediatric Tibial Shaft Fractures.
AB  - Tibial shaft fractures are one of the most common pediatric fractures. They
      require appropriate diagnosis and treatment to minimize complications and
      optimize outcomes. Diagnosis is clinical and radiological, which can be difficult
      in a young child or with minimal clinical findings. In addition to acute
      fracture, Toddler's and stress fractures are important entities. Child abuse must
      always be considered in a nonambulatory child presenting with an inconsistent
      history or suspicious concomitant injuries. Treatment is predominantly
      nonoperative with closed reduction and casting, requiring close clinical and
      radiological followup until union. Although there is potential for remodeling,
      this may not be adequate with more significant deformities, thus requiring
      remanipulation or rarely, operative intervention. This includes flexible
      intramedullary nailing, Kirschner wire fixation, external fixation, locked
      intramedullary nailing, and plating. Complications are uncommon but include
      deformity, growth arrest, nonunion, and compartment syndrome.

PMID- 30237609
TI  - Intrasubstance Anterior Cruciate Ligament Injuries in the Pediatric Population.
AB  - Pediatric intrasubstance anterior cruciate ligament (ACL) tears have a
      significant epidemiologic impact as their numbers continue to grow globally. This
      review focuses on true pediatric intrasubstance ACL tears, which occur >400,000
      times annually. Modifiable and non-modifiable risk factors include intercondylar
      notch width, ACL size, gender, landing mechanisms, and hormonal variations. The
      proposed mechanisms of injury include anterior tibial shear and dynamic valgus
      collapse. ACL tears can be associated with soft tissue and chondral defects.
      History and physical examination are the most important parts of evaluation,
      including the Lachman test, which is considered the most accurate physical
      examination maneuver. Imaging studies should begin with AP and lateral
      radiographs, but magnetic resonance imaging is very useful in confirming the
      diagnosis and preoperative planning. ACL injury prevention programs targeting
      high risk populations have been proven to reduce the risk of injury, but lack
      uniformity across programs. Pediatric ACL injuries were conventionally treated
      nonoperatively, but recent data suggest that early operative intervention
      produces best long term outcomes pertaining to knee stability, meniscal tear
      risk, and return to previous level of play. Current techniques in ACL
      reconstruction, including more vertically oriented tunnels and physeal sparing
      techniques, have been described to reduce the risk of physeal arrest and limb
      angulation or deformity. Data consistently show that autograft is superior to
      allograft regarding failure rate. Mean durations of postoperative therapy and
      return to sport were 7 +/- 3 and 10 +/- 3 months, respectively. These patients
      have good functional outcomes compared to the general population yet are at
      increased risk of additional ACL injury. Attempts at primary ACL repair using
      biological scaffolds are under investigation.

PMID- 30237612
TI  - Factors Responsible for Redisplacement of Pediatric Forearm Fractures Treated by
      Closed Reduction and Cast: Role of casting indices and three point index.
AB  - Background: Pediatric forearm fractures are still considered an enigma in view of
      their propensity to redisplace in cast. The redisplacement may be a potential
      cause for malalignment. We prospectively analyzed the role of risk factors and
      above casting indices in predicting significant redisplacement of pediatric
      forearm fractures treated by closed reduction and cast. Materials and Methods:
      113 patients of age range 2-13 years with displaced forearm fractures, treated by
      closed reduction and cast were included in this prospective study. Prereduction
      and postreduction angulation, translation, and shortening were noted. In
      addition, for distal metaphyseal fractures, obliquity angle was noted. In
      postreduction X-ray, apart from fracture variables, casting indices were also
      noted (cast index [CI] for all patients with three-point index [TPI] and second
      metacarpal radius angle in addition for distal metaphyseal fractures). In 2nd
      week, X-rays were again obtained to check for significant redisplacement. These
      patients were managed with remanipulation and casting or were operated if
      remanipulation failed. Comparison of various risk factors was made between
      patients with significant redisplacement and those which were acceptably reduced.
      A subgroup analysis of patients with distal metaphyseal fractures was done.
      Results: Thirteen (11.5%) patients had significant redisplacement; all of them
      required remanipulation. No association with respect to age, sex, level of
      fracture, side of injury, surgeon's experience, number of bones fractured, and
      injury to definitive cast interval was seen. The presence of complete
      displacement in any of the plane in either of the bones was seen to be highly
      significant predictor of redisplacement (P < 0.001). Postreduction angulation
      more than 10 degrees  in any plane in either of the bone and fracture obliquity
      angle in distal metaphyseal fracture also had a highly significant association
      with redisplacement. There was a significant difference in the mean values of all
      three casting indices assessed. TPI was the most sensitive casting index (87.5%).
      Conclusions: Conservative management with aim of anatomical reduction, especially
      in patients with complete displacement, should be the approach of choice in
      closed pediatric forearm fractures. Casting indices are good markers of quality
      of cast.

PMID- 30237611
TI  - Single Bone Fixation versus Both Bone Fixation for Pediatric Unstable Forearm
      Fractures: A Systematic Review and Metaanalysis.
AB  - Background: It is uncertain whether single bone fixation is comparable to both
      bone fixation in the treatment of unstable both bone forearm fractures in
      children. Materials and Methods: A systematic review using PubMed, Embase, and
      Cochrane Library database searches was performed on October 1, 2015 on English
      language scientific literature only. Clinical study designs comparing single bone
      fixation with both bone fixation of pediatric both bone forearm fractures were
      included. Studies of only one treatment modality were excluded from the study.
      Studies eligible for inclusion were assessed using the risk of bias tool for
      nonrandomized studies. Results: Metaanalysis points to no significant differences
      in re-angulation, loss of rotation, union time and complications between single
      bone and both bone fixation. However, the published research lacks quality.
      Conclusions: Despite scattered evidence and small sample sizes, the metaanalysis
      suggests single bone fixation can be considered a suitable alternative for both
      bone forearm fractures in children, as it carries less time in surgery and less
      cost without compromise in final functional outcome compared to double-bone
      fixation.

PMID- 30237613
TI  - Exposed versus Buried Kirschner Wires Used in Displaced Pediatric Fractures of
      Lateral Condyle of Humerus.
AB  - Background: Comparision of results and complications of exposed versus buried
      Kirschner wires (K-wires) after open reduction of lateral condyle fractures is
      scarce and mainly from western population; hence, we envisaged to study the
      safety and efficacy of exposed and buried K-wires used for fixation of displaced
      pediatric fracture of the lateral condyle of humerus in Indian setup. Materials
      and Methods: A prospective, nonrandomized, comparative study was conducted in 50
      patients with age <12 years, presenting with displaced fracture of lateral
      condyle of humerus of <2 weeks duration, without associated ipsilateral upper
      limb injury, who were treated by open reduction and internal fixation with either
      exposed or buried K-wires (n = 25 in each group). At a minimum followup of 3
      months, status of fracture reduction, union, evidence of osteomyelitis, carrying
      angle at the elbow, and elbow range of motion (ROM) were assessed
      clinicoradiologically. Results: Four (16%) patients in exposed group and 1 (4%)
      in buried group had superficial infection, while 3 (12%) patients in exposed
      group and 2 (8%) in buried group had deep infection. All the patients with
      infection responded well to oral antibiotics and regular dressings. Buried group
      had higher incidence of secondary skin and wire-related complications.
      Conclusion: There was no statistical difference between the two groups but
      exposed K wires are easy to remove so are preferred over buried K wires.

PMID- 30237614
TI  - Outcome Analysis of Lateral Pinning for Displaced Supracondylar Fractures in
      Children Using Three Kirschner Wires in Parallel and Divergent Configuration.
AB  - Background: Supracondylar humerus fracture is the most common fracture around
      elbow in children. Closed reduction and percutaneous Kirschner wire (pin)
      fixation is the standard method of managing displaced extension type (Gartland
      Type II and Type III) supracondylar humerus fractures. The configuration of wires
      is debatable. Although two crossed K-wires are mechanically stable, there is an
      inherent risk of ulnar nerve injury. Lateral K-wires - parallel or divergent -
      are good alternative. This study was aimed at identifying the best configuration
      for the lateral wires. Materials and Methods: Patients with Gartland type 3
      supracondylar humerus fractures were randomized by envelope method to receive
      closed reduction and K-wire fixation in either a parallel or divergent fashion.
      The patients were followed up at 3 weeks for wire removal and at 6 weeks and 3
      months after surgery. Baumann's angle, functional outcome as per Flynn's
      criteria, and range of motion were recorded in each visit. Effect of delay in
      surgery was also evaluated as a secondary outcome. Results: Nineteen patients
      received fixation with parallel wires and 11 patients had divergent fixation. No
      loss of reduction was seen in any patient at 3 months. No statistically
      significant difference was seen in the Baumann's angles and outcome according to
      Flynn's criteria irrespective of the wire configuration (divergent or parallel).
      Furthermore, the delay in surgery was also found not to have a significant effect
      on the functional outcome. Conclusions: Both parallel and divergent K-wire
      configurations provide satisfactory stability when accurate reduction and
      adequate fixation of the fracture has been done. Based on the limited number of
      patients in this study, one configuration cannot be judged to be superior to the
      other.

PMID- 30237615
TI  - Clinical and Radiographic Outcomes of Pediatric Radial Head Fractures.
AB  - Background: The treatment of pediatric radial head fracture (RHF) is
      controversial, and the outcome is unpredictable. We aimed to evaluate the long
      term clinical and radiographic outcomes of patients with pediatric RHF. Materials
      and Methods: 24 patients with pediatric RHFs operated between January 2004 and
      2012 were included in this retrospective study. 17 patients had extra articular
      radial head (EARH) fractures and 7 had intraarticular radial head (IARH)
      fractures. The Mayo Elbow Performance Score (MEPS), Tibone and Stoltz
      classification, range of motion (ROM), and carrying angle (CA) were evaluated.
      The radial head diameter (RHD) and radial head height (RHH), neck shaft angle
      (NSA), and distance from the radial head to the radial tuberosity (RHRT) were
      measured and compared with the other side in simple anteroposterior views of
      elbow radiographs. Results: At the last followup, the mean MEPS was 100 and 97.9
      in groups EARH and IARH, respectively. There were no clinically and
      radiographically significant differences between the groups. The injured elbows
      showed smaller ROMs than the uninjured elbows in flexion, supination, and
      pronation with statistically significant differences. However, the injured elbows
      showed larger extension ranges than the uninjured elbows with a statistical
      significance (all P = 0.000). CA, RHD, and RHH were higher in the injured elbows
      than in the uninjured elbows with statistically significant differences (P =
      0.006, 0.000, and 0.011) However, NSA and RHRT of both elbows were similar, with
      no statistically significant difference (P = 0.810 and 0.752). Conclusion: All
      patients with pediatric RHF were satisfied with the long term clinical results.
      The injured elbows showed restricted ROMs compared with the uninjured elbows;
      however, the extension range increased.

PMID- 30237616
TI  - Arthroscopic Excision of Osteoid Osteoma of the Femoral Neck.
AB  - Osteoid osteoma (OO) is a benign, solitary bone tumor of the long bones of the
      lower limbs and accounts for 10% to 12% of all benign bone. However, an OO of the
      femoral neck is extremely rare and difficult to treat. Arthroscopic excision of
      OO of the femoral neck has many advantages. We report a 15-year-old patient with
      OO of the femoral neck which was treated with arthroscopic excision. The clinical
      and radiographic findings along with the surgical management of the lesion are
      presented. The pain disappeared immediately after the operation. At the 14
      months' followup, the patient was pain free, and there was no evidence of
      recurrence.

PMID- 30237617
TI  - Legends of Indian Orthopedics: Dr. Verghese Chacko.

PMID- 30237618
TI  - Corrigendum: Results of crowe Type IV developmental dysplasia of hip treated by
      subtrochantric osteotomy and total hip arthroplasty.
AB  - [This corrects the article on p. 374 in vol. 52, PMID: 30078895.].

PMID- 30237619
TI  - Serum-binding properties of isosteric ruthenium and osmium anticancer agents
      elucidated by SEC-ICP-MS.
AB  - Abstract: Size-exclusion chromatography-inductively coupled plasma-mass
      spectrometry (SEC-ICP-MS) was used to study the serum-binding preferences of two
      metallodrugs with anticancer activities in vivo, namely the organoruthenium
      compound plecstatin-1 and its isosteric osmium analog. The complexes were
      administered intraperitoneally into mice bearing a CT-26 tumor. Comparing the
      total metal content of mouse whole blood and serum underlined that the
      metallodrugs are mainly located in serum and not in the cellular fraction of the
      blood samples. In mouse serum, both compounds were not only found to bind
      extensively to the serum albumin/transferrin fraction but also to
      immunoglobulins. Free drug was not observed in any of the samples indicating
      rapid protein binding of the metallodrugs. These findings were validated by
      spiking human serum with the respective compounds ex vivo. An NCI-60 screen is
      reported for the osmium analog, which revealed a relative selectivity for cancer
      cell lines of the ovary and the central nervous system with respect to plecstatin
      1. Finally, a COMPARE 170 analysis revealed disruption of DNA synthesis as a
      possible treatment effect of the osmium-based drug candidate. Graphical abstract:

PMID- 30237620
TI  - Regiospecific formation of the nitromethyl-substituted 3-phenyl-4,5
      dihydroisoxazole via [3 + 2] cycloaddition.
AB  - Abstract: 5-(Nitromethyl)-3-phenyl-4,5-dihydroisoxazole was obtained as a product
      of a high-yielding [3 + 2] cycloaddition reaction of in situ-generated
      benzonitrile N-oxide and 3-nitroprop-1-ene. For the first time, the
      regiochemistry of this reaction was unambiguously proven by X-ray structural
      analysis. The quantum-chemical calculation performed at the M06-2X/6-31G(d) (PCM)
      theoretical level affords a basis for explaining the course of reaction as well
      as the nature of transition states. Next, further DFT calculations together with
      spectral data shed light on structural aspects of the product. Graphical
      abstract: 

PMID- 30237622
TI  - PREFERENCE FOR THE WORKPLACE, INVESTMENT IN HUMAN CAPITAL, AND GENDER.
AB  - We use a hypothetical choice methodology to estimate preferences for workplace
      attributes from a sample of high-ability undergraduates attending a highly
      selective university. We estimate that women on average have a higher willingness
      to pay (WTP) for jobs with greater work flexibility and job stability, and men
      have a higher WTP for jobs with higher earnings growth. These job preferences
      relate to college major choices and to actual job choices reported in a follow-up
      survey four years after graduation. The gender differences in preferences explain
      at least a quarter of the early career gender wage gap.

PMID- 30237621
TI  - Synthesis of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives:
      anticancer activity, QSAR studies, and metabolic stability.
AB  - Abstract: A new series of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide
      derivatives have been synthesized and evaluated in vitro for their
      antiproliferative activity by MTT assay against cancer cell lines HCT-116, MCF-7,
      and HeLa as well as the NCI-60 human tumor cell lines screen. In NCI screen,
      three compounds inhibited approximately 50% growth of RPMI-8226 and A549/ATCC
      cell lines. The mean of IC50 calculated in MTT assays for three tested cell lines
      was about 45 MUM for four compounds. The QSAR allowed finding statistically
      significant OPLS models for HeLa cell line. Metabolic stability in vitro studies
      indicated favorable and unfavorable structural elements. The good metabolic
      stability, with t1/2 higher than 40 min, was observed for three derivatives,
      which together with their antiproliferative activity and good ADMET profile,
      makes them good leading structures for further research. Graphical abstract: 

PMID- 30237623
TI  - Interleukin 17 and Treg - a common pathomechanism and a new target of therapy in
      rheumatic diseases and depression.

PMID- 30237624
TI  - Tofacitinib in the treatment of patients with rheumatoid arthritis: position
      statement of experts of the Polish Society for Rheumatology.
AB  - Tofacitinib is a newly approved small-molecule targeted synthetic disease
      modifying antirheumatic drug. The drug was designed as a selective and specific
      inhibitor of pro-inflammatory receptor signalling. Tofacitinib inhibits the
      process of intracellular signalling from the receptor to the cellular nucleus and
      inhibits the inflammation process via a new pathway (inhibition of the Janus
      kinases), which is unavailable to biological medicines. Tofacitinib has been
      approved for use in the treatment of patients with moderate to severe active RA.
      The drug may be used in combination with methotrexate or another conventional
      synthetic disease-modifying antirheumatic drug or in monotherapy. The efficacy of
      tofacitinib has been confirmed in several clinical trials. The drug inhibits
      radiographic progression of the disease. The innovative mechanism of action of
      tofacitinib is a noteworthy feature because it offers hope of effective treatment
      for patients who fail to respond to other drugs. The presented article discusses
      the mechanism of action and the clinical application of tofacitinib. Tofacitinib
      represents a new group of disease-modifying antirheumatic drugs that can be
      placed on an equal footing with biological drugs already available.

PMID- 30237625
TI  - Pharmacoeconomic evaluation of treatment effectiveness with selected biologic
      treatment in rheumatoid arthritis therapy.
AB  - Objectives: Modern treatment of autoimmune diseases is becoming increasingly
      widely used. We owe it to the continuous and rapid development of biotechnology,
      molecular biology, immunology, and biochemistry. The proven effectiveness of
      biological therapy in rheumatoid arthritis (RA) should result in its widespread
      use. At present, only about 1% of patients with RA have access to biological
      therapy in Poland. Material and methods: The study material was retrospectively
      collected in the Rheumatology and Systemic Tissue Diseases Clinic and
      Rheumatology Outpatient Clinic in dr Jan Biziel University Hospital No. 2 in
      Bydgoszcz 2009-2014. Patients were divided into 3 groups: patient receiving
      infliximab, etanercept and adalimumab. Results: The study involved analyses of
      cost effectiveness. The time horizon of patient documentation analysis ranged
      from the time a patient was enrolled to infliximab, etanercept or adalimumab
      therapy until remission of the disease. The majority of patients achieved
      remission in the case of adalimumab treatment (85.29%), followed by etanercept
      (74.07%), then infliximab (37.21%). Taking into account the DAS28 parameter,
      analysis was performed using medical costs of the analyzed treatment regimens.
      For this purpose, the incremental cost-effectiveness ratio (ICER) was calculated.
      According to the analysis, obtaining one DAS28 unit, replacing infliximab with
      etanercept, would cost PLN 40 964 67. Higher costs would be required in the case
      of replacement of infliximab with adalimumab - PLN 43 076 08. Obtaining one
      additional DAS28 unit (in this case, a decrease in DAS28 by one unit) by
      introducing adalimumab instead of etanercept would amount to PLN 45 409 74.
      Conclusions: Undoubtedly, the pharmacoeconomic analysis makes it easier to decide
      on the appropriate treatment. Therefore, its implementation should be a widely
      used solution not only for RA, but also for other diseases. Health care and other
      entities' systems should also be improved in such a way that the data needed for
      pharmacoeconomic analysis are fully available.

PMID- 30237626
TI  - Factors of depression among patients with rheumatoid arthritis.
AB  - Objectives: The aim of this study was to assess the correlation between symptoms
      of depression and the course and clinical picture of rheumatoid arthritis (RA).
      Material and methods: 120 patients with RA were included in the study: 104 (87%)
      female patients and 16 (13%) male patients. All studied patients completed the
      following questionnaires: Beck Depression Inventory (BDI), Ford Insomnia Response
      to Stress Test (FIRST), Athens Insomnia Scale (AIS) and Health Assessment
      Questionnaire (HAQ). The serum levels of IL-1beta, TNF-alpha, and IL-6 were
      measured using standard ELISA assays at the time of the first questionnaire
      assessment. Results: Symptoms of depression were found in 91 patients (76%),
      including 79 (87%) women and 12 (13%) men. There were no significant differences
      between the prevalence of depression in women and men (p = 0.93). Symptoms of
      depression occurred more often in patients who were professionally inactive,
      compared with the professionally active patients (p = 0.04). Significant
      correlations was demonstrated between the value of BDI and the patient's pain
      assessed by the visual analogue scale (VAS) value (r = 0.36), the disease
      activity assessed by the patient and the physician evaluated in millimetres on
      the VAS scale (r = 0.38 and r = 0.30, respectively), the number of painful and
      swollen joints (r = 0.22 and r = 0.26, respectively), DAS28 (r = 0.31) as well as
      the Health Assessment Questionnaire (HAQ) value (r = 0.46). Longer duration of
      the disease was observed in patients with symptoms of depression (p = 0.02). Also
      a significant difference in the assessment of BDI between patients treated with
      biological drugs and those receiving no such treatment was observed (p = 0.042).
      Conclusions: Professional inactivity and longer disease duration are important
      factors influencing symptoms of depression in patients with RA. Higher values of
      HAQ increase the probability of the occurrence of depression symptoms. The use of
      biological drugs that reduce the level of proinflammatory cytokines may have a
      positive effect on reducing the severity of depressive symptoms.

PMID- 30237627
TI  - Comorbidities in rheumatic arthritis.
AB  - Objectives: Rheumatoid arthritis (RA) is one of the most common systemic
      inflammatory diseases, but its etiology is still not fully known. The aim of this
      preliminary study was to assess what particular comorbidities are involved in the
      progression of RA and determine the influence that the aforementioned diseases
      have on each other. Material and methods: Forty patients with diagnosed RA
      according to EULAR/ACR criteria from 2010 were included in the study. The
      majority of the group was female (n = 35; 87.5%). Patients were tested using
      routine laboratory and imaging methods allowing diagnosis and assessment of
      disease activity. Dual energy X-ray absorptiometry was also evaluated for mineral
      density. The activity of the disease was assessed using the disease activity
      score DAS28 (ESR) and SDAI (Simplified Disease Activity Index). Results: Among
      studied patients, based on the DAS28 index, 9 patients were in the remission
      phase (22.5%) and 12 (30%) had high disease activity. Increased values of CRP
      were observed in the majority of patients (65%). The group analysis demonstrated
      the most common comorbidities in patients with RA, as follows: hypertension (n =
      14; 35%) and osteoporosis or osteopenia (n = 13; 32.6%). Conclusions: Patients
      with rheumatoid arthritis (RA) are more susceptible to developing hypertension
      and osteoporosis. We did not observe a significant association between other
      comorbidities and activity of RA. The next study will assess a larger number of
      patients.

PMID- 30237628
TI  - Biosimilar switching - current state of knowledge.
AB  - Evidence from over 10 years of clinical experience demonstrates that biosimilar
      medicines approved in the European Union can be used for all their registered
      indications as safely as their originators and with no negative impact on
      therapeutic efficacy. The debate on the use of biosimilars in rheumatology
      focuses specifically on the safety of switching between biosimilars and reference
      products. Studies conducted to date, including randomised double-blind and open
      label extension trials, have not demonstrated any significant differences in
      therapeutic efficacy or safety between patients switched from one medicine to
      another and those who were continued on a single medicine. According to the
      latest recommendations for the use of biosimilars in rheumatic diseases,
      developed by an international task force in 2017, there is no clinical evidence
      that a single switch from an originator to a biosimilar medicine is associated
      with any significant risk for patient safety or reduction in therapeutic
      efficacy.

PMID- 30237629
TI  - Antinuclear antibodies in healthy people and non-rheumatic diseases - diagnostic
      and clinical implications.
AB  - The presence of antinuclear antibodies (ANA) is mainly associated with connective
      tissue diseases (CTD). In addition, their presence is found in healthy people.
      These antibodies are more common in women and the elderly. Some drugs and
      xenobiotics are also important for the development of autoimmunity and ANA
      synthesis. Moreover, the deficiency of vitamin D in the body of patients
      correlates with occurrence of these antibodies. Unlike the healthy group, a
      positive ANA count was observed in patients with atopic dermatitis (AD) and in
      people with immune disorders. Antinuclear antibodies in low counts are also found
      in the course of chronic bacterial or viral infection and in patients with
      hematological malignancies. Also the possibility of false positive results, which
      may be caused by the choice of method used to determine antibodies, should be
      borne in mind. Taking into account all these factors, it is concluded that the
      ANA result itself has no diagnostic value.

PMID- 30237630
TI  - Interstitial lung disease in systemic sclerosis: challenges in early diagnosis
      and management.
AB  - Interstitial lung disease (ILD) is a group of lung diseases characterized by
      thickening of the interstitium surrounding pulmonary alveolar walls. It is
      related to specific radiographic features in lung imaging and/or the presence of
      restrictive disorders in pulmonary function tests (PFTs). ILD is one of the
      leading causes of death in systemic sclerosis patients. Major risk factors of ILD
      associated with SSc (SSc-ILD) include male sex, diffuse type of cutaneous SSc and
      presence of anti-Scl-70 antibodies. SSc-ILD is challenging to diagnose at an
      early stage as the symptoms are non-specific. The greatest risk of its
      development is during the 4-5 years after the initial diagnosis of systemic
      sclerosis. Clinical vigilance at the time, including regular pulmonary function
      tests and/or high-resolution com-puted tomography (HRCT), is needed. The aim of
      this paper is to summarize the current knowledge on early diagnostic methods and
      progression risk factors for SSc-ILD.

PMID- 30237631
TI  - Systemic lupus erythematosus of the urinary tract: focus on lupus cystitis.
AB  - Systemic lupus erythematosus (SLE) frequently manifests as urinary tract disease,
      most commonly in the form of lupus nephritis. Bladder involvement in the disease
      course takes a subclinical form and may affect both children and adults. Lupus
      cystitis can precede SLE diagnosis and may present with very unspecific urinary
      and digestive tract symptoms or no symptoms at all. The exact mechanism of
      bladder inflammation in lupus is not fully understood; however, histopathological
      studies suggest a possible role of immune complex-mediated small vessel
      vasculitis. Lupus cystitis is a rare SLE manifestation, but poses a challenge for
      physicians, due to its complex diagnostics and treatment.

PMID- 30237632
TI  - The role of diet in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic connective tissue disease which develops
      in the course of an autoimmune inflammatory process triggered by environmental
      factors in a genetically predisposed person. One of the environmental factors is
      the diet. RA patients' adherence to a healthy diet remains low, despite plentiful
      data confirming positive effects of some foods, e.g. fish rich in n-3
      polyunsaturated fatty acids (PUFAs), as well as the negative influence of
      unhealthy eating patterns, such as high consumption of fats and sugars, on RA
      incidence, activity and treatment response. In this review, we present current
      knowledge on the role of diet in rheumatoid arthritis, including dietary factors'
      preventive/promoting influence on RA development, as well as their impact on RA
      activity. We hope this article will aid and encourage clinicians to recommend a
      relevant dietary intervention to their RA patients.

PMID- 30237633
TI  - Thrombotic thrombocytopenic purpura as the first presentation in systemic lupus
      erythematosus.
AB  - Thrombotic thrombocytopenic purpura (TTP) is an uncommon, life-threatening
      disease characterized by severe thrombocytopenia, microangiopathic haemolytic
      anaemia, neurologic abnormalities, renal insufficiency, and fever commonly
      associated with infections, malignancy, drugs, and autoimmune diseases.
      Coexistence of TTP with systemic lupus erythematosus (SLE) is extremely rare, and
      the emergence of the full manifestation of SLE starting with TTP is even rarer.
      Black people due to genetic risk factors are at increased risk of TTP. In the
      present article the authors describe the case of a Nigerian woman who developed
      classical features of TTP as the first manifestation of SLE. The patient's
      condition was stabilized after treatment with intravenous pulses of
      methylprednisolone and subsequently on oral prednisolone and hydroxychloroquine
      treatment.

PMID- 30237634
TI  - Comment on the article by Opeyemi Folorunsho Bamidele, Richard Oluyinka Akintayo,
      Mathew Olumuyiwa Bojuwoye, et al. "Thrombotic thrombocytopenic purpura as the
      first presentation in systemic lupus erythematosus".

PMID- 30237635
TI  - Treatment of Ammonium-Rich Digestate from Methane Fermentation Using Aerobic
      Granular Sludge.
AB  - Digestate produced by cofermentation of agricultural waste and manure can be
      difficult to dispose of because its high ammonium content impedes its use in
      agriculture due to generation of odor and overfertilization. This study
      investigated the possibility of treating such nitrogen-rich digestate with
      aerobic granular sludge depending on the nitrogen load in the reactor. At
      nitrogen loading rate of 1.0 g TN/(L.day), the nitrogen removal efficiency was
      high (64.9 +/- 9.8%), ammonium nitrogen was completely oxidized, and nitrate was
      the main nitrification product. At nitrogen loading rate of 3.4 g TN/(L.day),
      ammonium oxidization was still good (93.6 +/- 2.0%), but the percentage of
      partial nitrification was high (over 68%) and nitrogen removal efficiency
      worsened to 30.2 +/- 2.6%. Despite this, the overall amount of nitrogen removed
      was 0.86 g TN/(L.day) and was over nearly two times higher than at the lower
      nitrogen loading rate. At both nitrogen loading rates, in the effluent nitrogen
      in a form of suspended solids predominated. To diminish the overall N loading in
      the effluent, treatment is therefore recommended enabling removal of solids,
      e.g., microfiltration, should be applied, or the digestate should be separated
      into solid and liquid phases, and only the liquid fraction should be subjected to
      biological treatment. At high N load in aerobic granules, a very versatile
      community of N-metabolizing microorganisms was present. More than 50% of all
      bacteria in aerobic granules were able to metabolize nitrogen, and the
      predominant genera (35%) was Thauera, which indicated that stable ammonium
      removal was achieved mostly as a result of heterotrophic nitrification.

PMID- 30237636
TI  - Helical Multi-walled Carbon Nanotubes as an Efficient Material for the Dispersive
      Solid-Phase Extraction of Low and High Molecular Weight Polycyclic Aromatic
      Hydrocarbons from Water Samples: Theoretical Study.
AB  - The differences in effectiveness of multi-walled carbon nanotubes (MWCNTs) as the
      dispersive solid-phase extraction (dSPE) sorbent for the selective extraction of
      polycyclic aromatic hydrocarbons (PAHs) were explained on the basis of
      theoretical study. It was observed that for low molecular weight PAHs, the
      recoveries using non-helical and helical MWCNTs were similar. In contrary, for
      PAHs containing five or more aromatic rings, the extraction efficiency was higher
      using HMWCNTs than for non-helical ones. Principle component analysis (PCA) as
      well as providing structural parameters and interaction energies for adsorption
      processes (PAH + CNT -> PAH-CNT) have been used for this purpose. All the PAH +
      CNT -> PAH-CNT adsorption processes considered were found to be thermodynamically
      favorable. However, the adsorption energies (Eads) for PAHs and the helical
      carbon nanotube surface estimated for the B(a)P-HCNT and I(1,2,3-cd)P-HCNT are
      substantially less negative than those observed for PAH molecules interacting
      with the non-helical CNT. Namely, the Eads calculated in simulated aqueous
      environment for the B(a)P-MWCNT(6,2) and I(1,2,3-cd)P-MWCNT(6,2) were
      respectively - 43.32 and - 59.98 kcal/mol, while values of only - 7.75 kcal/mol
      (B(a)P-HCNT) and - 9.13 kcal/mol (I(1,2,3-cd)P-HCNT) were found for the
      corresponding PAH-HCNT systems. Therefore, we conclude that the replacement of
      MWCNTs with HCNTs leads to PAH-HCNT systems in which the interaction energies are
      much smaller than those estimated for the corresponding PAH-MWCNT systems.
      HMWCNTs are therefore recommended as the dSPE sorbent phase for the extraction of
      both low and high molecular weight PAHs from water samples.

PMID- 30237638
TI  - Integrated Hydrological and Geophysical Characterisation of Surface and
      Subsurface Water Contamination at Abandoned Metal Mines.
AB  - The mining and processing of metal ores in the UK has left a legacy of
      environmental degradation, and abandoned metal mines still pose a significant
      threat to terrestrial and fluvial environments. Flow gauging, water quality and
      geophysics were combined in an integrated assessment of surface and subsurface
      hydrological contamination at Esgair Mwyn, an abandoned mine in Ceredigion,
      Wales. Heavy metals discharged from the site are polluting downstream
      watercourses, leading to widespread Environmental Quality Standards (EQS)
      compliance failures. Through salt water dilution gauging and water quality
      sampling, a daily efflux of 876 g of heavy metals was calculated, with
      contaminant mobilisation occurring mainly in two primary surface streams draining
      an exposed tailings heap. Electrical resistivity tomography subsurface imaging
      found a seepage plane within the tailings lagoon wall, whilst the main tailings
      heap became increasingly saturated with depth. A large adjacent field also had a
      high potential to convey pollutants in solution, yet its morphological
      characteristics have limited transmission, as the area acts as a passive
      treatment type system. With remediation of already polluted water both difficult
      and expensive, this approach provides a cost-effective way to identify the
      origins and pathways of contaminants, informing mitigation strategies focussed on
      containment. Esgair Mwyn is not an isolated case, as abandoned metal mines
      release at least 860 t of heavy metals annually into UK water bodies. These
      techniques could reduce or prevent abandoned metal mine hydrological pollution
      for decades to come, and enable associated UK water bodies to comply with future
      water quality standards.

PMID- 30237639
TI  - Exploiting soil moisture, precipitation and streamflow observations to evaluate
      soil moisture/runoff coupling in land surface models.
AB  - Accurate partitioning of precipitation into infiltration and runoff is a
      fundamental objective of land surface models tasked with characterizing the
      surface water and energy balance. Temporal variability in this partitioning is
      due, in part, to changes in pre-storm soil moisture, which determine soil
      infiltration capacity and unsaturated storage. Utilizing the NASA Soil Moisture
      Active Passive Level-4 soil moisture product in combination with streamflow and
      precipitation observations, we demonstrate that land surface models (LSMs)
      generally underestimate the strength of the positive rank correlation between pre
      storm soil moisture and event runoff coefficients (i.e., the fraction of rainfall
      accumulation depth converted into stormflow runoff during a storm event).
      Underestimation is largest for LSMs employing an infiltration-excess approach for
      stormflow runoff generation. More accurate coupling strength is found in LSMs
      that explicitly represent sub-surface stormflow or saturation-excess runoff
      generation processes.

PMID- 30237640
TI  - Frozen in Place: Net Migration in sub-National Areas of the United States in the
      Era of the Great Recession.

PMID- 30237637
TI  - Greywater Characteristics, Treatment Systems, Reuse Strategies and User
      Perception-a Review.
AB  - This paper presents a literature review of the quality of greywater generated in
      different, especially developing, countries, constituents found in greywater,
      some treatment systems, natural materials for treatment, some reuse strategies
      and public perception regarding greywater reuse. The review shows that generation
      rates are mostly influenced by lifestyle, types of fixtures used and climatic
      conditions. Contaminants found in greywater are largely associated with the type
      of detergent used and influenced by other household practices. Many of the
      treatment systems reviewed were unable to provide total treatment as each system
      has its unique strength in removing a group of targeted pollutants. The review
      revealed that some naturally occurring materials such as Moringa oleifera,
      sawdust, can be used to remove targeted pollutants in greywater. The study
      further showed that user perceptions towards greywater treatment and reuse were
      only favourable towards non-potable purposes, mostly due to perceived
      contamination or lack of trust in the level of treatment offered by the treatment
      system.

PMID- 30237641
TI  - On entropy research analysis: cross-disciplinary knowledge transfer.
AB  - Our aim is to illustrate how the thermodynamics-based concept of entropy has
      spread across different areas of knowledge by analyzing the distribution of
      papers, citations and the use of words related to entropy in the predefined
      Scopus categories. To achieve this, we analyze the Scopus papers database related
      to entropy research during the last 20 years, collecting 750 K research papers
      which directly contain or mention the word entropy. First, some well-recognized
      works which introduced novel entropy-related definitions are monitored. Then we
      compare the hierarchical structure which emerges for the different cases of
      association, which can be in terms of citations among papers, classification of
      papers in categories or key words in abstracts and titles. Our study allowed us
      to evaluate, to some extent, the utility and versatility of concepts such as
      entropy to permeate in different areas of science. Furthermore, the use of
      specific terms (key words) in titles and abstracts provided a useful way to
      account for the interaction between areas in the category research space.

PMID- 30237642
TI  - Response to the letter 'Field classification of publications in Dimensions: a
      first case study testing its reliability and validity'.
AB  - With Dimensions, Digital Science provides the research community a new approach
      on research related information, bringing formerly siloed content types such as
      grants, patents, clinical trials with publications and citations together, making
      it as openly available as possible (see app.dimensions.ai). Due to the different
      content types, (controversial) journal based classifications were not an option
      since it would not allow to categorise grants etc. Hence Digital Science opted
      for applying a categorisation approach using machine learning and based on the
      content of the documents and well established classification systems for which a
      training set was available. The implementation at launch was a first step and
      requires to be improved-although we observe a reliability comparably to manual
      coding for grants, the implementation at launch comes with some shortcomings as
      observed by Bornmann (2018), mostly due to challenges with the training set
      coverage. To overcome the shortcomings of the initial categorization approach we
      implemented an improvement process with the research community and Lutz
      Bornmann's analysis presented a great opportunity to provide more transparency
      and insights in the ongoing improvements.

PMID- 30237643
TI  - Can't bibliometric analysts do better? How quality assessment without field
      expertise does not work: A comment on G. Madison and T. Soderlund: Comparisons of
      scientific quality indicators across peer-reviewed journal articles with more or
      less gender perspective: Gender studies can do better.
AB  - The article is an invited comment on Guy Madison and Therese Soderlund (M&S):
      Comparisons of content and scientific quality indicators across peer-reviewed
      journal articles with more or less gender perspective: Gender studies can do
      better. Scientometrics 115(3):1161-1183. The article pinpoints a series of
      serious problems in M&S's quantitative quality assessment and analysis of the
      field of gender studies, pertaining to their overall conceptual framework, their
      general approach and their specific analysis. It is argued that the over-arching
      problem in M&S's study is their lack of expert knowledge of the field of gender
      studies, their lack of respect for differences between qualitative and
      quantitative research, and their research design, which is biased towards
      quantitative social and natural science research. Firstly, it is demonstrated
      that a key concept, 'gender perspective', is used in an incoherent and confusing
      way in M&S's analysis. Secondly, it is argued that the confusion is not an
      isolated definitional problem, but related to a series of slippages between M&S's
      source of inspiration (Ganetz in Genusvetenskapliga projektansokningar inom
      humaniora-samhallsvetenskap - en uppfoljning av Vetenskapsradets beredning och
      utfall ar 2004. Vetenskapsradets rapportserie, Stockholm 15/2005, 2005) and their
      own adoption of the category. Thirdly, differences between qualitative and
      quantitative research, and between hermeneutic and explanatory knowledge
      production, are discussed more broadly to sustain the argument that the mentioned
      slippages occur, because M&S transfer analytical tools from Ganetz' qualitative
      study, based on a peer review methodology, to a quantitative quality assessment,
      carried out without field specific expert knowledge. It is argued that, to be
      adequate and relevant, a quality assessment would need to respect these
      differences, and develop tools and research designs accordingly. Fourthly, the
      validity of M&S's content analysis-the core of their study-is questioned in
      detail because of its use of inadequate analytical categories, and because of its
      exclusion of central elements from the analysis. Finally, it is argued that the
      bias in M&S's research design is reproduced in their results.

PMID- 30237644
TI  - A Continuous a-Stratification Index for Item Exposure Control in Computerized
      Adaptive Testing.
AB  - The method of a -stratification aims to reduce item overexposure in computerized
      adaptive testing, as items that are administered at very high rates may threaten
      the validity of test scores. In existing methods of a -stratification, the item
      bank is partitioned into a fixed number of nonoverlapping strata according to the
      items' a , or discrimination, parameters. This article introduces a continuous a 
      stratification index which incorporates exposure control into the item selection
      index itself and thus eliminates the need for fixed discrete strata. The new
      continuous a -stratification index is compared with existing stratification
      methods via simulation studies in terms of ability estimation bias, mean squared
      error, and control of item exposure rates.

PMID- 30237645
TI  - Constructing Shadow Tests in Variable-Length Adaptive Testing.
AB  - Imposing content constraints is very important in most operational computerized
      adaptive testing (CAT) programs in educational measurement. Shadow test approach
      to CAT (Shadow CAT) offers an elegant solution to imposing statistical and
      nonstatistical constraints by projecting future consequences of item selection.
      The original form of Shadow CAT presumes fixed test lengths. The goal of the
      current study was to extend Shadow CAT to tests under variable-length termination
      conditions and evaluate its performance relative to other content balancing
      approaches. The study demonstrated the feasibility of constructing Shadow CAT
      with variable test lengths and in operational CAT programs. The results indicated
      the superiority of the approach compared with other content balancing methods.

PMID- 30237646
TI  - Methods for Estimating Item-Score Reliability.
AB  - Reliability is usually estimated for a test score, but it can also be estimated
      for item scores. Item-score reliability can be useful to assess the item's
      contribution to the test score's reliability, for identifying unreliable scores
      in aberrant item-score patterns in person-fit analysis, and for selecting the
      most reliable item from a test to use as a single-item measure. Four methods were
      discussed for estimating item-score reliability: the Molenaar-Sijtsma method
      (method MS), Guttman's method lambda6 , the latent class reliability coefficient
      (method LCRC), and the correction for attenuation (method CA). A simulation study
      was used to compare the methods with respect to median bias, variability
      (interquartile range [IQR]), and percentage of outliers. The simulation study
      consisted of six conditions: standard, polytomous items, unequal alpha
      parameters, two-dimensional data, long test, and small sample size. Methods MS
      and CA were the most accurate. Method LCRC showed almost unbiased results, but
      large variability. Method lambda6 consistently underestimated item-score
      reliabilty, but showed a smaller IQR than the other methods.

PMID- 30237647
TI  - A Zero-Inflated Box-Cox Normal Unipolar Item Response Model for Measuring
      Constructs of Psychopathology.
AB  - This research introduces a latent class item response theory (IRT) approach for
      modeling item response data from zero-inflated, positively skewed, and arguably
      unipolar constructs of psychopathology. As motivating data, the authors use 4,925
      responses to the Patient Health Questionnaire (PHQ-9), a nine Likert-type item
      depression screener that inquires about a variety of depressive symptoms. First,
      Lucke's log-logistic unipolar item response model is extended to accommodate
      polytomous responses. Then, a nontrivial proportion of individuals who do not
      endorse any of the symptoms are accounted for by including a nonpathological
      class that represents those who may be absent on or at some floor level of the
      latent variable that is being measured by the PHQ-9. To enhance flexibility, a
      Box-Cox normal distribution is used to empirically determine a transformation
      parameter that can help characterize the degree of skewness in the latent
      variable density. A model comparison approach is used to test the necessity of
      the features of the proposed model. Results suggest that (a) the Box-Cox normal
      transformation provides empirical support for using a log-normal population
      density, and (b) model fit substantially improves when a nonpathological latent
      class is included. The parameter estimates from the latent class IRT model are
      used to interpret the psychometric properties of the PHQ-9, and a method of
      computing IRT scale scores that reflect unipolar constructs is described,
      focusing on how these scores may be used in clinical contexts.

PMID- 30237648
TI  - Leader autonomy support in the workplace: A meta-analytic review.
AB  - Leader autonomy support (LAS) refers to a cluster of supervisory behaviors that
      are theorized to facilitate self-determined motivation in employees, potentially
      enabling well-being and performance. We report the results of a meta-analysis of
      perceived LAS in work settings, drawing from a database of 754 correlations
      across 72 studies (83 unique samples, N = 32,870). Results showed LAS correlated
      strongly and positively with autonomous work motivation, and was unrelated to
      controlled work motivation. Correlations became increasingly positive with the
      more internalized forms of work motivation described by self-determination
      theory. LAS was positively associated with basic needs, well-being, and positive
      work behaviors, and was negatively associated with distress. Correlations were
      not moderated by the source of LAS, country of the sample, publication status, or
      the operationalization of autonomy support. In addition, a meta-analytic path
      analysis supported motivational processes that underlie LAS and its consequences
      in workplaces. Overall, our findings lend support for autonomy support as a
      leadership approach that is consistent with self-determination and optimal
      functioning in work settings.

PMID- 30237649
TI  - Multisession Cognitive Bias Modification Targeting Multiple Biases in Adolescents
      with Elevated Social Anxiety.
AB  - Research studies applying cognitive bias modification of attention (CBM-A) and
      interpretations (CBM-I) training to reduce adolescent anxiety by targeting
      associated cognitive biases have found mixed results. This study presents a new
      multi-session, combined bias CBM package, which uses a mix of training techniques
      and stimuli to enhance user-engagement. We present preliminary data on its
      viability, acceptability and effectiveness on reducing symptoms and biases using
      an A-B case series design. 19 adolescents with elevated social anxiety reported
      on their social anxiety, real-life social behaviours, general anxiety,
      depression, and cognitive biases at pre/post time-points during a 2-week baseline
      phase and a 2-week intervention phase. Retention rate was high. Adolescents also
      reported finding the CBM training helpful, particularly CBM-I. Greater reductions
      in social anxiety, negative social behaviour, and general anxiety and depression,
      characterised the intervention but not baseline phase. There was a significant
      correlation between interpretation bias change and social anxiety symptom change.
      Our enhanced multi-session CBM programme delivered in a school-setting appeared
      viable and acceptable. Training-associated improvements in social anxiety will
      require further verification in a study with an active control condition/group.

PMID- 30237650
TI  - Implicit Measures of Actual Versus Ideal Body Image: Relations with Self-Reported
      Body Dissatisfaction and Dieting Behaviors.
AB  - Body dissatisfaction refers to a negative appreciation of one's own body stemming
      from a discrepancy between how one perceives his/her body (actual body image) and
      how he/she wants it to be (ideal body image). To circumvent the limitations of
      self-report measures of body image, measures were developed that allow for a
      distinction between actual and ideal body image at the implicit level. The first
      goal of the present study was to investigate whether self-reported body
      dissatisfaction is related to implicit measures of actual and ideal body image as
      captured by the Relational Responding Task (RRT). Secondly, we examined whether
      these RRT measures were related to several indices of dieting behavior. Women
      high in body dissatisfaction (n = 30) were characterized by relatively strong
      implicit I-am-fat beliefs, whereas their implicit I-want-to-be-thinner beliefs
      were similar to individuals low in body dissatisfaction (n = 37). Implicit body
      image beliefs showed no added value over explicit body image beliefs in
      predicting body dissatisfaction and dieting behavior. These findings support the
      idea that the interplay between ideal and actual body image drives (self
      reported) body dissatisfaction. However, strong support for the view that it
      would be critical to differentiate between explicit and implicit body image
      beliefs is missing.

PMID- 30237651
TI  - Youth Perspectives on Sexuality Communication With Parents and Extended Family.
AB  - Objective: To explore extended-family sexuality communication and compare it with
      parent sexuality communication. Background: Family communication about sex can
      protect teens from sexual risk behavior. However, most studies on this topic
      focus exclusively on the parent-teen dyad; few capture the broader context of
      teens' family communication. Method: Using a mixed-methods approach, a
      convenience sample of 22 teens from diverse racial and ethnic backgrounds were
      interviewed. Participants were asked to identify family members with whom they
      talk about sex and relationships, topics discussed, messages shared, and the
      teens' comfort talking about sex and relationships. Thematic analysis was used to
      explore participants' shared meanings and experiences. Results: Eighty-six
      percent of teens reported talking with both parents and extended family about
      sex. Teens were more likely to report that parents than extended family shared
      messages about delaying sex and avoiding teen pregnancy and gave advice or shared
      information about sex. Teens were more likely to view extended family than
      parents as easy to talk with and as having shared life experiences, and some
      reported avoiding talk with parents about issues related to sexuality due to
      feeling awkward or fearing a negative reaction. Conclusion: Extended family may
      play a somewhat different role than parents in teens' sexuality communication,
      but family members showed a largely common set of family values. Implications:
      Extended family may be a valuable teen resource for sexuality communication,
      particularly when teens feel uncomfortable talking with parents.

PMID- 30237652
TI  - Human Perceptions of Megafaunal Extinction Events Revealed by Linguistic Analysis
      of Indigenous Oral Traditions.
AB  - Human settlement into new regions is typically accompanied by waves of animal
      extinctions, yet we have limited understanding of how human communities perceived
      and responded to such ecological crises. The first megafaunal extinctions in New
      Zealand began just 700 years ago, in contrast to the deep time of continental
      extinctions. Consequently, indigenous Maori oral tradition includes ancestral
      sayings that explicitly refer to extinct species. Our linguistic analysis of
      these sayings shows a strong bias towards critical food species such as moa, and
      emphasizes that Maori closely observed the fauna and environment. Temporal
      changes in form and content demonstrate that Maori recognized the loss of
      important animal resources, and that this loss reverberated culturally centuries
      later. The data provide evidence that extinction of keystone fauna was important
      for shaping ecological and social thought in Maori society, and suggest a similar
      role in other early societies that lived through megafaunal extinction events.

PMID- 30237653
TI  - Estimation of Sobol's Sensitivity Indices under Generalized Linear Models.
AB  - We derive explicit formulas for Sobol's sensitivity indices (SSIs) under the
      generalized linear models (GLMs) with independent or multivariate normal inputs.
      We argue that the main-effect SSIs provide a powerful tool for variable selection
      under GLMs with identity links under polynomial regressions. We also show via
      examples that the SSI-based variable selection results are similar to the ones
      obtained by the random forest algorithm but without the computational burden of
      data permutation. Finally, applying our results to the problem of gene network
      discovery, we identify though the SSI analysis of a public microarray dataset
      several novel higher-order gene-gene interactions missed out by the more standard
      inference methods. The relevant functions for SSI analysis derived here under
      GLMs with identity, log, and logit links are implemented and made available in
      the R package SobolSensitivity.

PMID- 30237654
TI  - Black locust (Robinia pseudoacacia) beloved and despised: a story of an invasive
      tree in Central Europe.
AB  - Robinia pseudoacacia, invaded many countries a long time ago and is now a common
      part of the Central European landscape. Positive economic but negative
      environmental impacts of Robinia result in conflicts of interest between nature
      conservation, forestry, urban landscaping, beekeepers and the public when
      defining management priorities. Because current legislation will determine the
      future distribution of Robinia in the landscape, a comprehensive view of this
      species is necessary. Although this species is well studied, most of the
      scientific papers deal with the economic aspects. Other information is published
      in local journals or reports. Therefore we reviewed the ecological and socio
      economic impact of Robinia placing particular emphasis on the species' history,
      vegetation ecology, invasiveness and management. In Central Europe, Robinia is
      limited climatically by late spring frost combined with a short vegetation
      period, soil hypoxia, shade and frequent major disturbances. The long historical
      tradition of using Robinia for afforestation has resulted in its popularity as a
      widespread forest tree and it being an important part of the economy in some
      countries. The main reasons are its fast growth, valuable and resistant wood,
      suitability for amelioration, reclamation of disturbed sites and erosion control,
      honey-making and recently dendromass production. On the other hand, a side-effect
      of planting this nitrogen-fixing pioneer tree, very tolerant of the nature of the
      substrate, is its propagation and spread, which pose a problem for nature
      conservation. Robinia is considered invasive, threatening especially dry and semi
      dry grasslands, some of the most species-rich and endangered types of habitat in
      the region, causing extinction of many endangered light-demanding plants and
      invertebrates due to changes in light regime, microclimate and soil conditions.
      Other often invaded habitats include open dry forests and shrubland, alluvial
      habitats, agrarian landscapes, urban and industrial environments and disturbed
      sites, e.g. post-fire sites, forest clearings or degraded forestry plantations.
      Without forestry, black locust abundance would decrease during succession in
      forests with highly competitive and shade tolerant trees and in mature forests it
      occurs only as admixture of climax trees. The limited pool of native woody
      species, lack of serious natural enemies and a dense cover of grasses and sedges
      can suppress forest succession and favour the development of Robinia monodominant
      stands over 70 years old. A stratified approach, which combines both tolerance in
      some areas and strict eradication at valuable sites, provides the best option for
      achieving a sustainable coexistence of Robinia with people and nature.

PMID- 30237655
TI  - Parent Preferences and Experiences with Psychological Treatment: Results from a
      Direct-to- Consumer Survey using the Marketing Mix Framework.
AB  - Direct-to-consumer (DTC) marketing strategies represent an increasingly popular
      approach to promote patient awareness of psychological treatments (PTs). The
      Marketing Mix is a well-established framework used to inform marketing decisions
      consisting of four "P's": Product (or Service), Promotion, Place, and Price. We
      conducted the first DTC marketing survey using the Marketing Mix framework to
      explore how parents concerned about their adolescents' behavioral health receive
      information about PTs. A sample of 411 parents (51% girls, 82% Non-Hispanic
      White) of 12- to 19-year-old adolescents completed an online survey asking how
      they would prefer to receive information about PTs, including five questions
      spanning the Promotion, Price, and Place dimensions of The Marketing Mix. A
      subsample of 158 parents also reported on how they had received PT information
      during their adolescent's most recent therapy experience, allowing us to compare
      ideal versus actual therapy experiences. We explored the extent to which
      experiences varied as a function of parent race/ethnicity, income per capita,
      parent education level, and adolescent treatment history. Bivariate analyses and
      multivariate logistic regressions were used to examine which of these variables
      were associated with parents' responses to specific survey items. Analyses
      revealed that parent preferences varied as a function of income per capita,
      education level, and history of treatment. In addition, there were significant
      gaps between parents' ideal and most recent therapy experiences. Implications for
      the marketing of PTs are discussed.

PMID- 30237656
TI  - A compendium of physical exercise-related human genes: an 'omic scale analysis.
AB  - Regular exercise is an exogenous factor of gene regulation with numerous health
      benefits. The study aimed to evaluate human genes linked to physical exercise in
      an 'omic scale, addressing biological questions to the generated database. Three
      literature databases were searched with the terms 'exercise', 'fitness',
      'physical activity', 'genetics' and 'gene expression'. For additional references,
      papers were scrutinized and a text-mining tool was used. Papers linking genes to
      exercise in humans through microarray, RNA-Seq, RT-PCR and genotyping studies
      were included. Genes were extracted from the collected literature, together with
      information on exercise protocol, experimental design, gender, age, number of
      individuals, analytical method, fold change and statistical data. The 'omic scale
      dataset was characterized and evaluated with bioinformatics tools searching for
      gene expression patterns, functional meaning and gene clusters. As a result, a
      physical exercise-related human gene compendium was created, with data from 58
      scientific papers and 5.147 genes functionally correlated with 17 Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathways. While 50.9% of the gene set
      was up-regulated, 41.9% was down-regulated. 743 up- and 530 down-regulated
      clusters were found, some connected by regulatory networks. To summarize, up- and
      down-regulation was encountered, with a wide genomic distribution of the gene set
      and up- and down-regulated clusters possibly assembled by functional gene
      evolution. Physical exercise elicits a widespread response in gene expression.

PMID- 30237657
TI  - The current use, and opinions of elite athletes and support staff in relation to
      genetic testing in elite sport within the UK.
AB  - The purpose of the study was to investigate the current use of genetic testing in
      UK elite sport and assess how genetic testing might be received by those employed
      in elite sport. Seventy-two elite athletes and 95 support staff at UK sports
      clubs and governing bodies completed an online survey of 11 questions concerning
      their experience of genetic testing and beliefs regarding the use of genetic
      testing in sport. Genetic testing related to sports performance and injury
      susceptibility is conducted in UK elite sport, albeit by a relatively small
      proportion of athletes (<=17%) and support staff (<=8%). Athletes and their
      support staff agree that genetics are important in determining elite status
      (>=79%) and appear willing to engage in genetic testing for individualising
      training to improve sport performance and reduce injury risk. Opinion was divided
      on whether genetic information should be used to identify talented athletes and
      influence selection, eligibility or employment status. Genetic testing for sports
      performance and injury susceptibility occurs in UK elite sport, however it is not
      commonly conducted. There is a belief that genetics is an important factor in
      determining an athlete and there is a willingness to engage in genetic testing
      for sports performance and injury susceptibility.

PMID- 30237658
TI  - Association between gene polymorphisms and obesity and physical fitness in Korean
      children.
AB  - Obesity is affected by genetic factors and environmental influences. This
      research was undertaken to identify single nucleotide polymorphisms (SNPs)
      related to obesity and physical fitness and then to analyse and compare
      interactions between physical fitness and obesity-associated genotypes. To
      investigate relationships between physical fitness and major SNPs previously
      reported to be related to obesity, 68 SNPs in 32 genes were genotyped in 71
      Korean children. Tests were conducted to evaluate five elements of physical
      fitness (speed, aerobic endurance, muscular endurance, muscular strength, and
      flexibility). The results obtained showed significant (P<0.02) differences in
      physical fitness scores for the following genotypes: CNR1 (rs1049353; GG), LEP
      (rs7799039; AA+AG), HHEX (rs1111875; TT), GC (rs16847015; TG+GG), LRP5
      (rs4988300; GG+GT), NPY2R (rs2880415; CT+CC), PPY (rs231472; GG), UCP2 (rs660339;
      CT+TT), CDKN2B (rs10811661; AA+AG), and ADIPOQ (rs266729; CG+GG). Ten physical
      fitness-related genotypes were newly identified during the present study. This
      study suggests that classification of genotypes by physical fitness level could
      be used as an index for predicting the risk of obesity and for selecting
      individuals for intervention programmes. Furthermore, the study shows that even
      children participating in the same physical fitness improvement programme can
      exhibit different genotype dependencies.

PMID- 30237659
TI  - Relationships between rating of perceived exertion, heart rate and blood lactate
      during continuous and alternated-intensity cycling exercises.
AB  - This study aimed to: i) use Borg's scale of rating perceived exertion (RPE) in
      the prescription of cycling training exercises with alternated intensity (S); ii)
      determine the relationships between RPE and the indices of physiological strains,
      e.g. heart rate (HR) and blood lactate ([La]), measured during S compared to
      continuous exercises (C). HR, [La] and RPE were measured in 11 active men at the
      5th and 10th minutes of cycling exercises. These exercises were performed with
      constant or varying intensity corresponding to average power outputs (APO) equal
      to 160 and 240 W. The protocols with varying intensity consisted of alternated
      short periods (10 s: S10, or 20 s: S20) of medium and high intensity (120-200 W
      for APO-160 W and 200-280 W for APO-240 W). During S exercises HR, [La] and RPE
      were significantly higher compared to C exercises. This effect was more
      pronounced when the duration of alternated-intensity bouts was longer (S20 versus
      S10 protocols). The relationships between HR, [La] and RPE (mean or individual
      data) were not significantly different for the different protocols. However,
      there was a shift in the relationship between RPE and HR measured at the 5th and
      10th minutes of exercise (p<0.001). Moreover, in each protocol, there were
      significant differences in the individual values of HR or [La] corresponding to
      the same RPE. The relationships between HR, [La] and RPE were not different
      between C and S exercises. Individually determined RPE can be used in the
      prescription of training for both exercises.

PMID- 30237660
TI  - Comparison of the effect of intermittent hypoxic training vs. the live high,
      train low strategy on aerobic capacity and sports performance in cyclists in
      normoxia.
AB  - The aim of the study was to compare the effect of intermittent hypoxic training
      (IHT) and the live high, train low strategy on aerobic capacity and sports
      performance in off-road cyclists in normoxia. Thirty off-road cyclists were
      randomized to three groups and subjected to 4-week training routines. The
      participants from the first experimental group were exposed to normobaric hypoxia
      conditions (FiO2 = 16.3%) at rest and during sleep (G-LH-TL; n=10; age: 20.5 +/-
      2.9 years; body height 1.81 +/- 0.04 m; body mass: 69.6 +/- 3.9 kg). Training in
      this group was performed under normoxic conditions. In the second experimental
      group, study participants followed an intermittent hypoxic training (IHT, three
      sessions per week, FiO2 = 16.3%) routine (G-IHT; n=10; age: 20.7 +/- 3.1 years;
      body height 1.78 +/- 0.05 m; body mass: 67.5 +/- 5.6 kg). Exercise intensity was
      adjusted based on the lactate threshold (LT) load determined in hypoxia. The
      control group lived and trained under normoxic conditions (G-C; n=10; age: 21.8
      +/- 4.0 years; body height 1.78 +/- 0.03 m; body mass: 68.1 +/- 4.7 kg; body fat
      content: 8.4 +/- 2.4%). The evaluations included two research series (S1, S2).
      Between S1 and S2, athletes from all groups followed a similar training programme
      for 4 weeks. In each research series a graded ergocycle test was performed in
      order to measure VO2max and determine the LT and a simulated 30 km individual
      time trial. Significant (p<0.05) improvements in VO2max, VO2LT, WRmax and WRLT
      were observed in the G-IHT (by 3.5%, 9.1%, 6.7% and 7.7% respectively) and G-LH
      TL groups (by 4.8%, 6.7%, 5.9% and 4.8% respectively). Sports performance (TT)
      was also improved (p<0.01) in both groups by 3.6% in G-LH-TL and 2.5% in G-IHT.
      Significant changes (p<0.05) in serum EPO levels and haematological variables
      (increases in RBC, HGB, HCT and reticulocyte percentage) were observed only in G
      LH-TL. Normobaric hypoxia has been demonstrated to be an effective ergogenic aid
      that can enhance the exercise capacity of cyclists in normoxia. Both LH-TL and
      IHT lead to improvements in aerobic capacity. The adaptations induced by both
      approaches are likely to be caused by different mechanisms. The evaluations
      included two research series (S1, S2). Between S1 and S2, athletes from all
      groups followed a similar training programme for 4 weeks. In each research series
      a graded ergocycle exercise test was performed in order to measure VO2max and
      determine the lactate threshold as well as a simulated 30 km individual time
      trial.

PMID- 30237661
TI  - Intermittent hypoxic training for 6 weeks in 3000 m hypobaric hypoxia conditions
      enhances exercise economy and aerobic exercise performance in moderately trained
      swimmers.
AB  - Athletic endurance performance at sea level can be improved via intermittent
      hypoxic training (IHT). However, the efficacy of IHT for enhancement of aerobic
      exercise performance at sea level is controversial because of methodological
      differences. Therefore, the aim of the study was to determine whether the IHT
      regimen ameliorates exercise economy and aerobic exercise performance in
      moderately trained swimmers. A total of 20 moderately trained swimmers were
      equally assigned to the control group (n=10) training in normoxic conditions and
      the IHT group (n=10) training at a simulated altitude of 3000 m. They were
      evaluated for metabolic parameters and skeletal muscle oxygenation during 30 min
      submaximal exercise on a bicycle, and aerobic exercise performance before and
      after 6 weeks of training composed of aerobic continuous exercise set at 80%
      maximal heart rate (HRmax) during 30 min and anaerobic interval exercise set at
      the exercise load with 90% HRmax measured in pre-test during 30 min (10 times 2
      min exercise and 1 min rest). According to the results, the IHT group
      demonstrated greater improvement in exercise economy due to decreases in VO2
      (p=.016) and HHb (p=.002) and increases in O2Hb (p<.001) and TOI (p=.006). VCO2
      was decreased in the IHT group (p=.010) and blood lactate level was decreased in
      the control (p=.005) and IHT groups (p=.001). All aerobic exercise performance
      including VO2max (p=.001) and the 400 m time trial (p<.001) were increased in the
      IHT group. The present findings indicate that the 6 week IHT regime composed of
      high-intensity aerobic continuous exercise and anaerobic interval exercise can be
      considered an effective altitude/hypoxic training method for improvement of
      exercise economy and aerobic exercise performance in moderately trained swimmers.

PMID- 30237662
TI  - Salivary total protein as a biomarker of anaerobic threshold in elderly athletes
      subjected to an incremental physical test.
AB  - : This study aimed to verify whether salivary total protein (STP) would reflect
      anaerobic threshold in elderly athletes subjected to an incremental exercise
      test. METHODS: Seven elderly elite athletes (EEA) and six physically active
      elderly men (PAE) completed a treadmill protocol in which blood and saliva
      samples were collected. RESULTS: Blood lactate (BL) and STP increased
      significantly in EEA during the test (0.8 +/- 0.2 to 5.1 +/- 2.0 mmol/L and 42.5
      +/- 7.5 to 222.5 +/- 63.8 mg/dL, respectively) and remained elevated at five
      minutes after exercise (5.0 +/- 1.9 mmol/L and 147.2 +/- 50.0 mg/dL,
      respectively). Furthermore, correlations between STP and heart rate (r = 0.87, p
      < 0.001), and between BL and STP (r = 0.96, p < 0.001), were observed in the
      elderly athletes. CONCLUSIONS: STP represents a potential non-invasive biomarker
      for determining anaerobic threshold during an incremental exercise test, and this
      parameter may be used as an indicator of physical exercise intensity in elderly
      athletes.

PMID- 30237663
TI  - Effects of intensity distribution changes on performance and on training loads
      quantification.
AB  - The present study analyses the effects of the high-intensity distribution change
      within sessions on physical performance and on training loads (TL) provided by
      quantification methods based on heart rate (HR) and on whole body indicators of
      exercise-induced physiological stress. Fourteen trained physical education
      students (21.9+/-1.2 years, 68.3+/-7.9 kg, 180+/-7.3 cm) performed two sessions
      with the same intensities, volumes and pauses but differing in the efforts'
      intensity distribution: one was composed of exercises dissociating the
      intensities (12 repetitions of 30 m sprints then 12 min interval runs) and the
      second mixed the intensities (30 m sprint followed by 60 s rest and 2 runs of 15
      s - 15 s at 100% and 50% of maximal aerobic velocity - MAV). Session TL was
      calculated using methods based on heart rate zones, training impulse, ratings of
      perceived exertion (session RPE) and endurance limit. Session-induced fatigue was
      observed using performances in repeated sprints and counter-movement jumps. The
      heart rate zone method provided higher TL for the mixed session (p=0.007), while
      training impulse described similar TL for the two sessions (p=0.420). The
      endurance limit method showed borderline significantly higher TL in dissociated
      sessions (p=0.058) and session RPE provided similar but the largest differences
      between sessions' TL (p=0.001). The dissociated session induced larger losses in
      counter-movement jumps (p=0.010) but lower speed decreases in sprints (p=0.007).
      Change in intensity distribution within sessions induced contradictory effects on
      performances and on TL quantification according to the method used. When high
      intensities are programmed, methods based on heart rate may present limitations
      for TL quantification, as such methods based on whole body indicators of exercise
      induced physiological stress should be preferred.

PMID- 30237664
TI  - Physical responses of professional soccer players during 4 vs. 4 small-sided
      games with mini-goals according to rule changes.
AB  - The aim of this study was to investigate the influence of the number of ball
      touches authorised per game (one touch [T1], two touches [T2], and free touches
      [FT]) on the players' physical responses throughout the bouts in 4 vs 4 soccer
      small-sided games (SSGs) with mini-goals (without a goalkeeper). Fourteen
      professional Polish players (age 23.2+/-2.7 years, height 177.9+/-6.1 cm, weight:
      73.2+/-6.9 kg, body fat 12.6+/-2%, playing experience: 14+/-5 years) completed
      nine series of 4 vs 4 SSGs. Each trial included three series of SSGs with a game
      duration of 4 minutes on an equal sized pitch (30x24 m; 720 m2; individual
      occupied area per player=90 m2). Differences in physical responses and time
      motion characteristics of players were measured with the Global Positioning
      System (GPS) and assessed using a repeated measures ANOVA to compare the three
      game conditions and the magnitude-based inference to evaluate the pairwise
      comparison effects. The results showed that only the variables distance covered
      at low speed, time walking, time at low speed, and accelerations of >4 m/s2 were
      statistically significantly different among game conditions. The pairwise
      comparisons only identified significant effects for distance covered at low speed
      (between FT and T2), for time walking (between FT and T1), for time at moderate
      and low speed (between FT and T2), and for accelerations of >4 m/s2 (between FT
      and T1). The players' performances are affected by the ball touch constraint
      during SSGs with mini-goals. The results provide useful information for training
      and task design that replicate specific physical demands (i.e., accelerations of
      >4 m/s2, time walking or running at a lower speed).

PMID- 30237665
TI  - Isokinetic moment curve abnormalities are associated with articular knee lesions.
AB  - The aim of this study was to test whether lesions of the medial meniscus (MM) and
      of the anterior cruciate ligament (ACL) are associated with specific
      abnormalities of isokinetic moment curves (IMCs). Fifty-four young adults (20
      active healthy people, and 34 patients with unilateral knee injuries) were
      assessed through knee extensor and flexor isokinetic tests at 60 degrees /s.
      Qualitative IMC analysis was performed using a novel classification system which
      identified three distinct abnormal shapes. The chi-squared (chi2) test was used
      to determine the inter-individual and intra-individual differences between the
      groups. Quantitative IMC inter-group comparisons were performed by a one-way
      analysis of variance (ANOVA). Knees with MM and ACL lesions were consistently
      associated with IMC shape irregularities (p<0.001) and with abnormal quantitative
      scores (p<0.001). More specifically, knees with isolated ACL lesions and knees
      with combined ACL and MM lesions presented similar distribution of knee extensor
      and flexor IMC irregularities, which was not present in knees with isolated MM
      lesions. A possible association between specific knee pathologies and IMC
      irregularities was identified (all p<0.05). In conclusion, different knee
      pathologies may be associated with different qualitative IMCs, which could be
      used as an additional presentation tool in clinical settings.

PMID- 30237667
TI  - Neurofeedback for the enhancement of dynamic balance of judokas.
AB  - Physical balance is an important factor in sport. Neurofeedback (EEG biofeedback)
      can be used to improve concentration and focus. The present study investigated
      and determined the impact of neurofeedback training on dynamic balance in judo.
      Eighteen judokas voluntarily participated in this study. The participants were
      divided into two groups: experimental (EG) and control (CG). In the experimental
      group subjects were trained to inhibit 3-8 Hz while they were also trained to
      reinforce 14-19 Hz brainwave activities at points O1 and O2 for ten sessions and
      25 minutes per session. The participants in the control group were exposed to the
      same conditions but instead were provided with sham feedback. EEG and dynamic
      balance tests were executed before and at the end of the fifteenth session of
      training. The one-way ANOVA with repeated measures revealed that dynamic balance
      scores significantly improved at the post-test (F=12.4, p=0.001) in the EG group.
      The findings demonstrate that neurofeedback training can enhance dynamic balance
      of judokas.

PMID- 30237666
TI  - Comparison of two warm-up models for obese and normal-weight adults performing
      supramaximal cycling exercise.
AB  - This study examines the impact of two forms of active warm-up on supramaximal
      cycling performance among sedentary adults. Thirty-seven adults [23.05 (6.4)
      years; BMI=26.05 (1.3) kg/m2, FM=30.1 (4.2)%, VO2max=23.8 (5.8) ml/min/kg]
      participated in a cross-over randomized study, and all underwent a supramaximal
      cycling test (SCT) following 5 minutes of two models of warm-up pedalled at a
      constant velocity of 60 rpm. In the first experimental condition, the warm-up was
      set at 50% of maximal aerobic power (WU50%MAP). In the second experimental
      condition, the intensity was set at 50% of maximal heart rate (WU50%MHR). During
      both experimental conditions the rating of perceived exertion (RPE) at the end of
      the warm-up and the performance reduction in percentage (DeltaPr%) during the SCT
      were recorded. During the WU50%MAP experimental condition, obese (OB) adults
      showed higher values of post-warm-up heart rate (~30%) than in the normal weight
      (NW) group (p<0.01). In addition, the RPE scores determined after the warm-up
      were significantly higher in OB compared to NW (~30%; p<0.01). However, after the
      WU50%MHR experimental condition, no significant differences remained between OB
      and NW. Moreover, the analyses showed a significant positive association between
      the elevated heart rate values observed after WU50%MAP and both RPE and DeltaPr%
      (r= 0.71 and r =0.81, p <0.05 respectively). In contrast to NW individuals, the
      WU50%MHR seems to be more suitable for the OB group undergoing the SCT given that
      WU50%MAP affected supramaximal cycling performances.

PMID- 30237668
TI  - Treatment of aortic aneurysms registered in Swedvasc: Development reflected in a
      national vascular registry with an almost 100% coverage.
AB  - Swedvasc is a registry for vascular surgical procedures, both open and
      endovascular. It was started in 1987 and since 1994 the whole population of
      Sweden is covered, at present around 10 million inhabitants. In a recent external
      validation, it was found to be highly accurate with abdominal aortic aneurysm
      surgery correctly reported in >96%. In this paper various factors explaining the
      almost 100% coverage are discussed, one important being that the registry has
      been developed and maintained within the profession of vascular surgery and not
      dictated by authorities. Another factor of importance is the possibility to use
      data in various research projects and so far 15 PhD theses have used Swedvasc
      data. To exemplify the practical use of the registry, the treatment of abdominal
      aortic aneurysms is scrutinized and among the various complications abdominal
      compartment syndrome is analyzed. Several significant temporal changes have been
      observed over the almost 25 years of Swedvasc: increasing use of endovascular
      surgery, treatment of aneurysms detected by screening , decreasing treatment for
      rupture, improved outcome, increasing treatment of older patients and patients
      with comorbid conditions. In conclusion, a high quality national vascular
      registry can be valid with high compliance and can be used to study population
      based development of treatment and outcome. It can also be used to perform
      international comparisons with other registries, thereby getting an indication of
      the quality of care.

PMID- 30237669
TI  - Why I use both prospective randomized trials and registry data when choosing the
      personalized treatment of an AAA patient.
AB  - Randomized controlled trials (RCTs) have been the core of level 1 data in medical
      and surgical science for at least the last three decades. However, frequently
      patient selection is very narrow, anatomic criteria do not match real-world
      experience, and much of the work is done in selected academic centers. We use
      RCTs to help explain the rational for intervention and then rely on longitudinal
      registries and single center data to give the patients a real-world expectation
      concerning outcomes and complications in our hands.

PMID- 30237670
TI  - Mechanical and elution properties of G3 Low Viscosity bone cement loaded up to
      three antibiotics.
AB  - Objective: Periprosthetic Joint Infection (PjI) is considered one of the most
      difficult complication to manage after total knee or hip arthroplasty, with a
      mean incidence of 1%. Antibiotic loaded bone cement is used as prophylaxis during
      primary arthroplasty and as local therapy during two-stage revision. The aim of
      this study is to evaluate the mechanical and elution properties of G3 Low
      Viscosity Bone Cement (G-21 San Possidonio, Modena, Italy) loaded with different
      doses of up to three antibiotics (12 specimens). Methods: Compressive Strength,
      Bending Strength and Bending Modulus were evaluated. Cumulative Vancomycin
      elution by adding different doses of antibiotics was evaluated. Results: The mean
      Compressive Strength was 81.55 MPa, the mean Bending Strength was 2161.7 MPa, and
      the mean Bending Modulus was 36.6 MPa. The highest cumulative Vancomycin elution
      was observed in specimen 12 (1906.9 mg at 2 weeks). This is the first study, at
      our knowledge, that analysed how cement mechanical properties, and antibiotic
      elution kinetics, are modified by adding up to three antibiotic. Conclusion: The
      results obtained in this pilot study using G3 Low-Viscosity Bone Cement,
      demonstrated that mechanical properties not decrease significantly by adding
      large doses of antibiotics, while the Vancomycin elution increase until swelled
      to twice.

PMID- 30237671
TI  - A review on the nutritional, medicinal, molecular and genome attributes of Durian
      (Durio zibethinus L.), the King of fruits in Malaysia.
AB  - Durian (Durio zibethinus L.; Family Bombacaceae) is an iconic tropical fruit
      plant cultivated in Malaysia and the Southeast Asian countries. In Malaysia,
      durian is recognised as the King of fruits and well known as a rich source of
      volatile sulphur compounds that make it unique. Fruit pulp of this fruit is an
      excellent source of nutrients as it contains proteins, dietary fat, fibers, and
      carbohydrates. Durian leaf and root decoctions are known to have a febrifuge and
      anti-malarial properties. The understanding of this plant's molecular biology
      will help breeders to develop a strategy for its further improvements. Hence,
      there is a need to identify and understand the genes necessary for the quality
      improvement of the durian fruits. Its genome contains about 46,000 genes which is
      almost double that of humans (Homo sapiens). The understanding of durian genes
      will be useful not only in the molecular breeding but also in the microbial
      production of novel proteins and or enzymes. This review highlights nutritional
      and medicinal attributes of durian. The molecular studies including the
      importance of undertaking transcriptomics work and the insights from the most
      recently reported genome draft are also highlighted.

PMID- 30237673
TI  - Binding property of HIV p24 and Reverse transcriptase by chalcones from Pongamia
      pinnata seeds.
AB  - HIV remains a challenging life threatening viral agent for humans despite
      available anti HIV drugs. The known effective drug named HAART clears the
      circulating viruses but not the intracellular viruses. Therefore, it is of
      interest to identify molecules with improved anti-HIV activity from natural plant
      sources. Hence, we studied the anti-HIV potency of an Indian medicinal plant
      named Pongamia pinnata. Aqueous extracts were made from leaf, seed and roots of
      Pongmia pinnata and screened for anti HIV-1 activity using HIV-1 p24 and reverse
      transcriptase (RT) inhibition assays. Further, the active chalcone derivatives
      namely, P24 protein and RT enzymes showed promising binding score against
      Glabarachalcone and Karanijin. Among these extracts, P. pinnta aqueous seed
      extracts have shown HIV-1 p24 inhibition at 66.9 +/- 4.4 percentage. However, RT
      inhibition assay showed only 36.8%. Hence, the HIV-1 p24 inhibition infers either
      the prevention of virus entry or inhibits other enzymes and or interferes with
      virion assembly.

PMID- 30237672
TI  - Biodegradation effects of o-cresol by Pseudomonas monteilii SHY on mustard seed
      germination.
AB  - Cresols are ubiquitous due to industrial production and natural presence. o
      cresol (2-methyl phenol) is highly toxic to both fauna and flora. It has been
      included in the EPA list as one of the priority pollutants. The deleterious
      effects of pesticides, herbicides, and many other chemical compounds on seed
      germination are known. However, the effect of o-cresol on seed germination is not
      known. Therefore, it is of interest to study the effect of o-cresol on
      germination of 13 different vegetable crop seeds using standard Filter Paper
      Method. There is no effect on germination for brinjal, red chili, and (green
      gram, chickpea, cucumber, tomato, fenugreek, cowpea, Green pea, coriander, and
      spinach, seeds even at 1500 mg/l of o-cresol However, okra and mustard were found
      to be sensitive to ocresol. Germination of mustard under controlled concentration
      of o-cresol showed similar results by soil method. It was found that germination
      percentage and seedling vigour (Vigour Index) was reduced by o-cresol. The
      percent germination was reduced to 64 and 12 at 25 and 50 mg o-cresol/kg soil as
      against 100% in the case of untreated control. The vigour index was reduced to
      160 and 10, respectively as against of 646 that for the control. The viability of
      seeds by 2,3,5 - tetrazolium trichloride (TTC) test showed that a considerable
      reduction was observed at 200mg/l o-cresol. Reduced protease and amylase activity
      in o-cresol shows inhibited mustard generation. However, mustard generation
      inhibition was restored by the bioremediation of o-cresol using Pseudomonas
      monteilii SHY. Thus, the biodegradation effects of o-cresol by Pseudomonas
      monteilii SHY on mustard seed germination are shown.

PMID- 30237674
TI  - Screening, Purification and Characterization of Protease Inhibitor from Capsicum
      frutescens.
AB  - Plants are rich in protease inhibitors (PI) and trypsin inhibitors are the most
      common. Therefore, it is of interest to screen PI from plant sources. We report
      the screening, purification and characterization of PI from Capsicum frutescenes.
      The partially purified PI showed bands corresponding to 21 KDa and was further
      confirmed using reverse zymography. The enzyme was stable at temperatures below
      60 degrees C and a wide range of pH with 65 folds purification. The effect of
      magnesium ions oxidizing and reducing agents on PI is reported. The large-scale
      isolation and purification of PI from Capsicum frutescenes is of commercial
      interest.

PMID- 30237676
TI  - Screening, isolation and characterization of biosurfactant producing Bacillus
      subtilis strain ANSKLAB03.
AB  - Biosurfactants are surface-active compounds produced by a wide range of
      microorganisms. They have both hydrophobic and hydrophilic domains and can
      decrease the surface tension and the interfacial tension of growth medium.
      Biosurfactants have different chemical structures like-lipopeptides, glycolipids,
      neutral lipids and fatty acids. They are biodegradable non-toxic biomolecules
      that show strong emulsification of hydrophobic compounds. They have the ability
      to form stable emulsions. The low water-solubility of these compounds restricts
      their availability to microorganisms. Surfactants secreted by microbes enhance
      the bioavailability of such hydrophobic compounds for bioremediation. Therefore,
      biosurfactant-enhanced solubility of pollutants has prospective applications in
      bioremediation. Biosurfactants are useful in a variety of industrial processes,
      and are also of vital importance to the microbes in adhesion, emulsification, and
      bioavailability, desorption and defense strategy. Therefore, it is of interest to
      identify biosurfuctantproducing strain of bacteria from brackish water. The
      microbial samples were isolated from the Chilika Lake, odisha, India and were
      tested for its biosurfactant property by various biochemical methods. 16S rRNA
      was sequenced using Sanger dideoxy sequencing method to characterize the
      biosurfuctant producing strain. The new Bacillus subtilis strain ANSKLAB03
      isolated from 40 samples was deposited in GenBank with accession number KU523257.

PMID- 30237677
TI  - Comparative analysis of prokaryotic and eukaryotic transcription factors using
      machine-learning techniques.
AB  - The DNA-protein interactions play vital roles in the central dogma of molecular
      biology. Proper interactions between DNA and protein would lead to the onset of
      various biological phenomena like transcription, translation, and replication.
      However, the mechanisms of these well-known processes vary between prokaryotic
      and eukaryotic organisms. The exact molecular mechanisms of these processes are
      unknown. Therefore, it is of interest to report the comparative estimate of the
      different properties of the DNA binding proteins from prokaryotic and eukaryotic
      organisms. We analyzed the different sequence-based features such as the
      frequency of amino acids and amino acid groups in the proteins of prokaryotes and
      eukaryotes by statistical measures. The general pattern of differences between
      the various DNA binding proteins for the development of a prediction system to
      discriminate between these proteins between prokaryotes and eukaryotes is
      documented.

PMID- 30237675
TI  - Computational studies on Begomoviral AC2/C2 proteins.
AB  - Geminiviridae is a large family of circular, single stranded DNA viruses, which
      infects and causes devastating diseases on economically important crops. They are
      subdivided into nine genera. Members of the genus begomovirus encode a pathogenic
      protein called AC2/C2 which interacts that inactivates many plant proteins and
      trans-activates a number of host genes via the C-terminal transactivation domain.
      Hence, a sequence analysis on C-terminal region of AC2/C2 was completed. Analysis
      of 124 bipartite and 463 mono partite begomo viral AC2/C2 proteins revealed major
      differences in protein length, composition and position of acidic, aromatic and
      hydrophobic residues. Secondary structure analysis of AC2/C2 revealed the
      possible formation of C-terminal alpha-helix, which is similar to the acidic
      activation domain of many transcriptional activator proteins. Previous studies
      demonstrated that AC2 utilizes conserved late element (CLE) for the
      transactivation of viral genes and genome-wide mapping of same consensus in A.
      thaliana yielded 122 promoters with exact CLE consensus sequence. Analysis of
      protein interaction network for 106 CLE containing genes, 87 AC2 trans activated
      genes and 10 AC2 interacting proteins revealed a possible regulation of hundreds
      of host proteins which helps begomoviruses to produce a successful viral
      infection.

PMID- 30237678
TI  - Designing novel inhibitors against Mycobacterium tuberculosis FadA5 (acetyl-CoA
      acetyltransferase) by virtual screening of known anti-tuberculosis (bioactive)
      compounds.
AB  - By-products of fatty acid degradation are extensively utilized by Mycobacterium
      tuberculosis (Mtb) for lipid synthesis and energy production during the infection
      phase. Cholesterol from host is scavenged by Mtb to fulfill its metabolic
      requirements, evade host immunity and invade macrophages. Blocking cholesterol
      catabolic pathways leads to bacteriostasis. FadA5 (Acetyl-CoA acetyltransferase),
      a thiolase encoded by fadA5 (Rv3546) gene in Mtb, plays a crucial role in
      cholesterol aliphatic chain degradation. Hence, FadA5 is a potential target for
      designing antitubercular inhibitors. In this study, 60,284 anti-tuberculosis
      (bioactive) compounds from ChEMBL database and analogous library from ZINC
      database of commercially available compounds have been screened against FadA5
      active site to identify compounds having inhibitory potential against both the
      apo (state I) and the intermediate (state II) states of FadA5. Altogether, this
      study reports 7 potential inhibitors against two functional states of FadA5,
      which can be further taken for invitro studies.

PMID- 30237680
TI  - Astrobiology - an opposing view.
AB  - The use of quantum computers and Artificial Intelligence (AI) is imperative for
      use in space exploration and astrobiology investigations. Considerable progress
      has been made since the commencement of origin of life laboratory and theoretical
      studies in the mid 20th century. However, the sheer amount of data amassed to
      date in all these studies including exoplanetary and astrobiological studies is
      enormous and increasing steadily. Thus, there is the need for AI and quantum
      computers. As AI develops, it will become crucial in the development of the
      statistical and database programs that are indispensable to analyze the huge
      quantity of cumulative data. Diverse biotic and geochemical processes have been
      shown to produce methane on the Earth. Elsewhere in the solar system, on other
      planets (e.g. Mars) and moons (e.g. Titan), as well as on exoplanets, abiotic
      processes are considered the primary sources of methane. Astronomers and astro
      biologists infer that the presence of methane supports the possibility of the
      presence of at least microbial life. In addition, on the Earth, there are also
      degradative reactions that include smog-related compounds and hazes that are
      produced as artefacts of intrinsic methane geochemistry as well as due to human
      footprint. Astronomers and astro-biologists envision life, away from the Earth,
      elsewhere in the solar system and on exoplanets, to occur under conditions
      similar or related to terrestrial life (goldilocks zone) conditions. These
      properties that are compatible with life as we know it on the Earth, include
      planetary orbits, gravitation, star radiant energy, presence of liquid water, and
      compatible temperatures and pressures, found on Earth. Generally,
      extraterrestrial life is also considered to resemble the biochemistry, molecular
      biology, and physiology of life on Earth - thus the focus on detection of
      supposed biosignatures of microbial life that resemble the Earth's. Nevertheless
      a crucial factor is absent in these deliberations - viruses. On the Earth,
      viruses that infect Archaea and bacteria form local and widespread global
      ecosystems. These viruses play a crucial role and facilitate the molecular
      transfer of host genes among various hosts. This essential function is
      underestimated in evolutionary as well as astrobiological speculations. Thus, it
      is of substantial importance to consider the roles that viruses may have played
      during the origin of life as well as in any exobiology.

PMID- 30237679
TI  - Linking common non-coding RNAs of human lung cancer and M. tuberculosis.
AB  - Lung cancer and pulmonary tuberculosis caused by Mycobacterium are two major
      causes of deaths worldwide. Tuberculosis linked lung cancer is known. However,
      the precise molecular mechanism of Mycobacterium associated increased risk of
      lung cancer is not understood. We report 45 common human miRNAs deregulated in
      both pulmonary tuberculosis and lung cancer. We show that sRNA_1096 and sRNA_1414
      from M. tuberculosis have sequence homology with human mir-21. Hence, the
      potential role of these three small non-coding RNAs in rifampicin resistance in
      pulmonary tuberculosis is implied. Further, the linking of sRNA_1096 and
      sRNA_1414 from M. tuberculosis with the host lung tumorigenesis is inferred.
      Nonetheless, further analysis and validation is required to associate these three
      non-coding RNAs with Mycobacterium associated increased risk of lung cancer.

PMID- 30237681
TI  - Orthosiphon stamineus Benth. is an Outstanding Food Medicine: Review of
      Phytochemical and Pharmacological Activities.
AB  - Orthosiphon stamineus Benth. (Lamiaceae) is a valued medicinal plant in
      traditional folk medicine. Many pharmacological studies have demonstrated the
      ability of this plant to exhibit antimicrobial, antioxidant, hepatoprotection,
      antigenotoxic, antiplasmodial, cytotoxic, cardioactive, antidiabetic, anti
      inflammatory activies. This review is a comprehensive summary of the presently
      available chemical, pharmacological investigations as well as the traditional and
      therapeutic uses of this plant. Important and different experimental data have
      been addressed along with a review of all phytochemicals identified in this
      plant, including flavonoids, terpenoids, and essential oils. O. stamineus has
      wide traditional and pharmacological uses in various pathophysiological
      conditions. Therefore, it is an attractive subject for further experimental and
      clinical investigations.

PMID- 30237682
TI  - An Insight and Update on the Analgesic Properties of Vitamin C.
AB  - Pain is an unpleasant subjective feeling having implications on both physical and
      mental realm. Multiple dimensions of pain involving behavioral, spiritual,
      emotional, and cognitive changes have been studied and pathways elucidated. It is
      stressed that the nature in which pain is modulated and perceived at a higher
      center is a complex phenomenon. One of the main goals of pain modulation is to
      modify pain to a more tolerable level, rather than its complete eradication.
      Different pain management interventions were tried but have effects that are more
      adverse. Till date, the only reliable pain blockers are analgesics and anti
      inflammatory drugs in the form of opioids and non-opioids. Despite this, most of
      the drugs are ineffective at various levels, furthermore, adding to
      complications. Thus, there is an urgent need for effective intervention with
      minimal side effects. Ascorbic acid, popularly known as vitamin C, has shown to
      exhibit promising analgesic properties. The literature is sparse with the usage
      of the drug in various forms of pain. This review focuses on the dynamics and
      kinetics of vitamin C and its usage in various forms of pain. With minimal
      adverse effects, the drug is shown to perform well in different types of pain
      disorders, thus paving way for alternative interventional agent for pain
      management.

PMID- 30237683
TI  - Sports Pharmacology: A Medical Pharmacologist's Perspective.
AB  - Abuse of substances or methods to enhance the performance is becoming very common
      in the sports, which often destroys the spirit of competition. The regulatory
      bodies for sports have reported rates ranging from 5% to 31% for the use of
      performance-enhancing substances among athletes. Athletes can have serious
      injuries and morbidities, leading to poor health with the use of such substances.
      Commonly abused agents in sports include anabolic-androgenic steroids and its
      analogs, blood, erythropoietin, growth hormone and its derivatives, nutritional
      supplements, creatine, amphetamines, beta-hydroxy-beta-methylbutyrate (HMB),
      stimulants, and analgesics. Health-care professionals need to be careful while
      prescribing medicines to sportspersons. Knowledge of exercise physiology,
      pharmacology of the commonly used agents for sports-related injuries, and agents
      used for doping could help the sportspersons and health-care professionals to
      avoid the embarrassment arising because of misuse of these agents. Sports
      pharmacology includes study of the various aspects of the drug use and abuse in
      sports and treatment of sports-related injuries. Focusing on sports pharmacology
      in the medical curriculum can help the upcoming health-care professionals to
      support the sportspersons to improve the quality of their life by using various
      drugs and other substances within the standardized limits and avoid embarrassment
      of doping.

PMID- 30237685
TI  - Pharmaceutico-analytical Study of Kushtae Shangarf Prepared with Jozbua
      (Myristica fragrans Houtt.) and Phitkari (Alum).
AB  - Introduction: Kushta of Shangarf (KS) is in therapeutic use since long time in
      Unani and Ayurvedic medicine. It requires extensive assessment with respect to
      its safety and processing because of the presence of mercury. KS prepared with
      Shangarf (HgS), Phitkari (alum), and Jozbua (Myristica fragrans Houtt.) was
      selected for the study. It is indicated as tonic, increases blood production, and
      improves complexion of face. Preparation of KS by classical and contemporary
      method and its comparative physicochemical analysis was attempted in this work.
      Materials and Methods: Kushta was prepared by incinerating the drugs kept inside
      Buta in Bhatti with 24kg of Uple (cow-dung cakes) and also in muffle furnace.
      Samples obtained were evaluated by Unani specifications (test), powder
      characterizations, loss on drying, pH, ash value, solubility, particle size, and
      qualitative estimation of organic and inorganic constituents, X-ray diffraction
      (XRD), quantitative estimation by inductively coupled plasma-mass spectrometry
      and inductively coupled plasma-optical emission spectrometry, and so on. Results:
      Physicochemical standards set in were comparable in KS prepared by classical
      method (KSCM) and in KS prepared by muffle furnace method (KSMFM), except water
      soluble ash and solubility in water were found slightly more in KSMFM. XRD study
      revealed the presence of aluminum oxide phase and absence of mercury in both the
      samples. Quantitative estimation of elements in both the samples in decreasing
      order are as follows: sulfur > aluminum > calcium > iron > arsenic. Arsenic was
      found more than iron in KSCM at parts per million level. Conclusion: Preliminary
      understanding suggests that muffle furnace method could be a better option with
      respect to safety and ease of preparation. Shangarf incinerated above 900 degrees
      C with Phitkari and Jaiphal did not show presence of mercury in both the samples,
      indicating KS prepared by incinerating at higher temperature can be safer than
      unroasted preparation. Studied formulation can be recommended or used for its
      indications without the concern of mercury toxicity.

PMID- 30237684
TI  - Potential Deoxycytidine Kinase Inhibitory Activity of Amaryllidaceae Alkaloids:
      An In Silico Approach.
AB  - Background: Plants of the Amaryllidaceae family have been under intense scrutiny
      for the presence of a couple of alkaloidal secondary metabolites with endued
      cytotoxic activity, such as pancratistatin (1), 7-deoxypancratistatin (2),
      narciclasine (3), 7-deoxynarciclasine (4), trans-dihydronarciclasine (5), and 7
      deoxy-trans-dihydronarciclasine (6). Nevertheless, preclinical evaluation of
      these alkaloids has been put on hold because of the limited quantity of materials
      available from isolation. Aim: To explore the underlying cytotoxic molecular
      mechanisms of the Amaryllidaceae alkaloids (1-6) and to assess their absorption,
      distribution, metabolism, excretion, and toxicity (ADMET) profiles using
      chemoinformatic tools. Materials And Methods: AutoDock 4.0 software along with
      different in silico chemoinformatic tools, namely PharmMapper, Molinspiration,
      MetaPrint2D, and admetSAR servers, were used to assess the drugability of the
      Amaryllidaceae alkaloids (1-6). Results: Deoxycytidine kinase (dCK) (PDB: 1P60)
      was predicted as a potential target with fitting score of 5.574. In silico
      molecular docking of (1-6) into dCK revealed good interactions, where interesting
      hydrogen bonds were observed with the amino acid residues-Gly-28 and Ser-35
      located in the highly conserved P-loop motif. This motif plays a special role in
      dCK function. Contrary to (1), in silico pharmacokinetic results have shown good
      absorption and permeation and thus good oral bioavailability for (2-6).
      Conclusion: The in silico docking data have proposed that the reported cytotoxic
      activity of the Amaryllidaceae alkaloids (1-6) could be mediated through dCK
      inhibition. In addition, the ADMET profile of these alkaloids is promising and
      thus (1-6) could be candidates for future drug development.

PMID- 30237686
TI  - Ethnopharmacological Uses and Public Knowledge Regarding Cinnamomum zeylanicum in
      Khobar, Saudi Arabia.
AB  - Background: Cinnamon (Cinnamomum zeylanicum) is a herb that is used traditionally
      as a flavoring agent as well as for its health benefits in different parts of the
      world. Its use may vary among cultures. Aim: To observe the knowledge and uses
      regarding cinnamon in the Saudi population. Materials and Methods: A 2-month
      cross-sectional study was conducted in Khobar, Saudi Arabia, using a novel
      questionnaire in Arabic language. Results: A total of 585 responses were
      collected. Most respondents were female (91.5%), adults (74.4%), married (65.6%),
      and had bachelor's degree (58.1%). A total of 84.3% knew about cinnamon and used
      cinnamon as bark (38.6%) and as a flavoring agent (74.7%). Most common reason for
      use was to ease menstruation and menstrual pain (49.9%), as antidiabetic (35.9%),
      and for weight loss (5.6%). The source of information for cinnamon use and its
      knowledge was family and relatives who were using cinnamon (75.9%), that is,
      folkloric use. Conclusion: Folkloric use of cinnamon was found to influence the
      knowledge and usage of cinnamon in the Saudi population.

PMID- 30237688
TI  - School Climate, Academic Achievement and Educational Aspirations in Roma Minority
      and Bulgarian Majority Adolescents.
AB  - Background: School climate can promote students' academic achievement and high
      educational aspirations. School climate refers to the quality and character of
      school life, norms, values, social interactions and organizational processes
      within a school. Objective: We examined for the present sample whether (a) school
      climate relates to academic achievement and educational aspirations and (b) such
      relations vary for Roma minority compared to their majority peers. Method:
      Participants in this cross-sectional study were 356 adolescents aged 11-19 years
      old (159 Roma, 197 Bulgarian majority), 332 mothers (149 Roma, 183 majority), 231
      fathers (104 Roma, 127 majority) and 221 majority teachers who completed self
      report surveys to address the study goals. Adolescents provided data on
      educational aspirations and academic achievement, parents on their children's
      educational aspirations and teachers reported on school climate. We employed
      linear mixed models to explore associations of school climate, academic
      achievement and educational aspirations among Roma and Bulgarian majority youth.
      Results: There were negative associations between teacher-reported school climate
      and students' academic achievement, as well as adolescent and parental
      educational aspirations for Roma adolescents only. Roma adolescents and parents
      reported lower academic achievement and educational aspirations than their
      majority counterparts. Conclusions: This study supports the relevance of school
      climate in relation to academic achievement and aspirations of disadvantaged
      minority students. Interventions should pay close attention to perceptions and
      attitudes in a school to successfully promote positive outcomes among students.

PMID- 30237687
TI  - A Survey on Human T-cell Lymphotropic Virus Type 1 (HTLV-1) and Xenotropic Murine
      Leukemia Virus-Related Virus (XMRV) Coinfection in Tehran, Iran.
AB  - Background: Xenotropic murine leukemia virus-related virus (XMRV) is a gamma
      retrovirus, which has been detected in patients with prostate cancer, chronic
      fatigue syndrome, and general population with a number of acquired infections
      such as infection with human T-cell lymphotropic virus (HTLV) and human
      immunodeficiency virus (HIV). The aim of this study was to determine the HTLV-1
      and XMRV coinfection for the first time in Iranian patients who were admitted to
      the Tehran hospitals. Materials and Methods: Two hundred and ninety one patients
      suspected with HTLV-1 were referred to the hospitals affiliated to the Iran
      University of Medical Sciences, Tehran, Iran from April 2012 to October 2016.
      Genomic deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) from peripheral blood
      mononuclear cells/cerebrospinal fluids was extracted by High Pure Viral Nucleic
      Acid Kit (Roche, Germany). After complementary DNA synthesis, conventional
      reverse transcriptase polymerase chain reaction was used for the detection of
      HTLV-1 or XMRV-infected patients. Statistical Package for Social Sciences (SPSS)
      software, version 16 (SPSS, Chicago, IL, USA) was used for statistical analyses.
      Results: Of the 291 patients suspected of HTLV infection, 123 (42.3%) were male
      with a mean age of 38+/-15 years. HTLV-1 RNA was found in 93 (31.9%) specimens
      comprising 40 men (41.3%) and 53 women (56.9%). Of the 93 patients who were HTLV
      1 positive, one sample (1%) was positive for XMRV env gene. Conclusion: These
      findings suggest that the lack of significant detection of XMRV in patients who
      were HTLV-1 positive could not be associated with complications of HTLV-1.
      Although this is a preliminary report from Iranian patients with HTLV-1, further
      studies are needed to show the actual prevalence of XMRV infection by
      geographical distribution and various populations.

PMID- 30237690
TI  - Cortisol level and suicidal risk.

PMID- 30237689
TI  - Readmissions Among Sepsis Survivors: Risk Factors and Prevention.
AB  - Hospital readmissions are common and result in increased mortality and cost while
      reducing quality of life. Readmission rates have been subjected to increasing
      scrutiny in recent years as part of a larger effort to improve the quality and
      value of healthcare in the United States. Emerging evidence suggests that sepsis
      survivors are at high risk for hospital readmission and experience readmission
      rates comparable to survivors of congestive heart failure, acute myocardial
      infarction, pneumonia, and chronic obstructive pulmonary disease, diseases whose
      readmission rates determine reimbursement penalties from the federal government.
      In this article, we review the unique challenges that sepsis survivors face as
      well as the patient-level and hospital-level risk factors that are known to be
      associated with hospital readmission after sepsis survival. Additionally, we
      identify the causes and outcomes of readmissions in this population before
      concluding with a discussion of readmission prevention strategies and future
      directions.

PMID- 30237691
TI  - Sleep disturbances in diabetic peripheral neuropathy patients: a clinical and
      polysomnographic study.
AB  - Background: Disordered sleep breathing is a common complication of diabetic
      peripheral neuropathy (DPN) manifested by excessive daytime sleepiness, morning
      headache, morning dizziness, cognitive decline, and mood changes. Methods: This
      study was performed on 30 non-obese type 2 diabetic patients; 20 with clinically
      evident DPN and 10 without. Ten age-, sex-, and body mass index-matched healthy
      control subjects were also included. Patients and control were subjected to
      history taking, neurological examination, glycated hemoglobin, and clinical
      assessment of the sensori-motor manifestations by the neuropathy symptom score
      and neuropathy disability score. The autonomic nervous system was evaluated
      clinically by the systolic blood pressure response to standing and heart rate
      response to each of standing, Valsalva, and deep breath. Finally, sleep was
      assessed by one-night polysomnogram (PSG) followed by multiple sleep latency test
      in the next day. Results: The study showed significant increase in sleep apnea
      syndromes in diabetic peripheral neuropathy patients compared to diabetic
      neuropathy free patients and healthy control (p < 0.0001). The sleep apnea was
      mainly obstructive and to a little extent mixed (obstructive/central) sleep
      apnea. The severity of sleep PSG abnormalities was positively correlated with the
      severities of sensory, motor, and autonomic manifestations. Conclusions: Non
      obese type 2 diabetic patients complicated by peripheral neuropathy especially
      those having dysautonomia are at increased risk of developing sleep disordered
      breathing resulting in their excessive daytime sleepiness, decreased
      productivity, and poor glycemic control.

PMID- 30237692
TI  - Relation between migraine pattern and white matter hyperintensities in brain
      magnetic resonance imaging.
AB  - Background: Migraine is a common disorder in general population. Presence of
      white matter hyperintensities (WMHs) in brain MRI of migraine patients was not
      studied clearly. Detection of the prevalence of white matter hyperintensities in
      migraine patients determines its correlation with migraine severity, type and
      duration. Methods: Cross sectional analytic study was conducted on migraine
      patients attending neurology clinic Suez Canal University Hospital. Sixty-five
      patients with migraine aged from 18 to 50 years were included. We excluded
      smokers and patients with hypertension, cardiac disease, diabetes mellitus,
      endocrine dysfunction, oncological and hematological diseases, infectious
      diseases, demyelinating disorders, and Alzheimer disease. Brain MRI and
      laboratory investigation was done for all patients. Results: White matter
      hyperintensities were significant more frequent in migraine with aura than those
      without aura. According to MIGSEV scale, white matter hyperintensities were
      highly significantly more frequent in grade III severity than grades II and I.
      The number of white matter hyperintensities increases significantly with increase
      intensity of pain during attack. The number of white matter hyperintensities
      increases significantly with increase intensity of nausea, disability,
      tolerability during attack and age. Resistance to treatment also shows
      statistically significant difference in increase number of WMHs. Conclusions:
      White matter hyperintensities are present in 43.1% of migraine patients. Age,
      presence of aura, nausea, disability during attack, resistance to treatment, and
      severity of headache and duration of migraine are considered a risk factor for
      development of white matter hyperintensities.

PMID- 30237693
TI  - Initiation and maintenance of a Treat-and-Extend regimen for ranibizumab therapy
      in wet age-related macular degeneration: recommendations from the UK Retinal
      Outcomes Group.
AB  - The treatment of neovascular (wet) age-related macular degeneration (AMD) with
      ranibizumab is now very well established in terms of efficacy and safety. Recent
      clinical trials and real-world studies have demonstrated the advantages of a
      Treat-and-Extend (T&E) regimen, and many hospital departments are now in the
      process of adopting this new regimen in favor of the pro re nata regimen for
      initiating and continuing ranibizumab therapy for patients with wet AMD. The
      comprehensive spectrum of issues related to implementation of the regimen is
      covered qualitatively in ten didactic topics provided by a group of clinicians
      with direct experience of this regimen in their department. The topics include
      definition, new and previously treated eyes, management of high-frequency
      injections, maximum extensions, discontinuing T&E, bilateral cases, clerical,
      audit, and patient counseling. This article aims to provide a useful resource for
      the implementation of the T&E regimen. A quantitative summary of the visual
      outcomes in key publications is also provided in this article. This article
      should be a valuable resource for staff training.

PMID- 30237694
TI  - Uncorrected visual acuity, postoperative astigmatism, and dry eye symptoms are
      major determinants of patient satisfaction: a comparative, real-life study of
      femtosecond laser in situ keratomileusis and small incision lenticule extraction
      for myopia.
AB  - Purpose: To compare factors affecting patient satisfaction after femtosecond
      laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction
      (SMILE) for myopia in the real-life situation study. Methods: The SMILE group
      included 100 eyes (51 patients) and the FS-LASIK group 200 eyes (102 patients).
      In addition to clinical examination, dry eye symptoms and patient satisfaction
      with far and near vision were reported and graded on the visual analog scale
      preoperatively and one month after the operation. Case-control pairs were
      selected for the SMILE patients from FS-LASIK-treated patients to ensure the
      homogeneity in spherical equivalent refraction, preoperative dry eye, and visual
      satisfaction. Results: Eighty percent of SMILE eyes and 83% of FS-LASIK eyes
      achieved an uncorrected distance visual acuity of 20/20 or better. Predictability
      (+/-0.5 D of mean target spherical equivalent refraction) was 91% in SMILE and
      93.5% in FS-LASIK. No eyes lost two or more Snellen lines of corrected distance
      visual acuity. Based on case-control pairs, dry eye symptoms remained the same
      after one month in the FS-LASIK-treated eyes (P=0.87) but decreased in the SMILE
      treated eyes (P=0.01) compared with the preoperative situation. Patient
      satisfaction with far vision improved significantly in both groups (P<0.001), but
      satisfaction with near vision improved significantly only in FS-LASIK (P<0.001)
      and not in SMILE (P=0.58). There was more postoperative astigmatism in SMILE in
      comparison with FS-LASIK (P=0.002). Conclusions: In a real-life situation,
      patients with preoperative dry eye experience were often directed to the SMILE
      operation, which resulted in beneficial decrease in their dry eye symptoms.
      Patient satisfaction with far vision decreased with increasing dry eye symptoms
      and postoperative astigmatism in both SMILE- and FS-LASIK-treated emmetropic
      patients. Safety, efficacy, and predictability were comparable in both
      treatments.

PMID- 30237695
TI  - Comparison of optical biometry versus ultrasound biometry in cases with
      borderline signal-to-noise ratio.
AB  - Purpose: To ascertain if optical biometry determination of axial length (AL) and
      intraocular lens (IOL) power is significantly different compared to ultrasound
      (US) biometry in cases with borderline signal-to-noise ratio (SNR). Patients and
      methods: Sixty patients who had cataract and IOL Master biometry with borderline
      SNR (1.6-2.0) were included. A retrospective chart review was performed to
      compare data collected with optical biometry and US biometry in cataract cases
      with borderline SNR. Results: Results showed that optical biometry IOL and AL
      measurements were not significantly different from the US measurements. Analysis
      also demonstrated good agreement between the two methods. Conclusion: Our study
      suggests that, in cases of borderline quality data, IOL power and AL measurements
      with optical biometry are still useful in surgical planning and that additional
      US measurements may be used more as a corroborative tool.

PMID- 30237696
TI  - Profile of atezolizumab in the treatment of metastatic non-small-cell lung
      cancer: patient selection and perspectives.
AB  - Programed cell death-1/programed death ligand-1 (PD-1/PD-L1) blockade represents
      an affirmed reality in the treatment of advanced non-small-cell lung cancer
      (NSCLC) patients. Atezolizumab, an anti-PD-L1 agent, figures among the drugs that
      provide previously unenvisaged outcomes in the pretreated setting of metastatic
      NSCLC. Increasing evidence vouches for the early administration of PD-1/PD-L1
      blockers in untreated patients, encompassing atezolizumab combinations with
      chemotherapy and the anti-angiogenic agent bevacizumab. Moreover, the development
      of atezolizumab allowed to derive several hints regarding clinical and
      immunological factors predictive of its activity and efficacy, some of them
      exclusive among this class of drugs. This review provides an overview of
      atezolizumab development throughout clinical trials toward its applicability in
      the routine practice, with a particular focus on patient selection based on
      clinical and immune-related factors.

PMID- 30237697
TI  - Eremomycin pyrrolidide: a novel semisynthetic glycopeptide with improved
      chemotherapeutic properties.
AB  - Purpose: Development of new semisynthetic glycopeptides with improved
      antibacterial efficacy and reduced pseudoallergic reactions. Methods:
      Semisynthetic glycopeptides 3-6 were synthesized from vancomycin (1) or
      eremomycin (2) by the condensation with pyrrolidine or piperidine. The minimum
      inhibitory concentration (MIC) for the new derivatives was measured by the broth
      micro-dilution method on a panel of clinical isolates of Staphylococcus and
      Enterococcus. Acute toxicity (50% lethal dose, maximum tolerated doses),
      antibacterial efficacy on model of systemic bacterial infection with S. aureus
      and pseudoallergic inflammatory reaction (on concanavalin A) of eremomycin
      pyrrolidide (5) were evaluated in mice according to standard procedures. Results:
      The eremomycin pyrrolidide (5) was the most active compound and showed a high
      activity against Gram-positive bacteria: vancomycin-susceptible staphylococci and
      enterococci (minimum inhibitory concentrations [MICs] 0.13-0.25 mg/L), as well as
      vancomycin-intermediate resistant Staphylococcus aureus (MICs 1 mg/L).
      Antimicrobial susceptibility tested on a panel of 676 isolates showed that 5 had
      similar activity for the genera Staphylococcus and Enterococcus with MIC90=0.5
      mg/L, while vancomycin had MIC90=1-2 mg/L. The number of resistant strains of
      Enterococcus faecium (vancomycin-resistant enterococci) (MIC =64 mg/L) with this
      value was 7 (8%) for vancomycin (1) and 0 for the compound 5. In vivo comparative
      studies in a mouse model of systemic bacterial infection with S. aureus
      demonstrated that the efficacy of 5 was notably higher than that of the original
      antibiotics 1 and 2. In contrast to 1, compound 5 did not induce pseudoallergic
      inflammatory reaction (on concanavalin A). Conclusion: The new semisynthetic
      derivative eremomycin pyrrolidide (5) has high activity against staphylococci and
      enterococci including vancomycin-resistant strains. Compound 5 has a higher
      efficacy in a model of staphylococcal sepsis than vancomycin (1) or eremomycin
      (2). In striking contrast to natural antibiotics, the novel derivative 5 does not
      induce a pseudoallergic inflammatory reaction to concanavalin A and therefore has
      no histamine release activity. These results indicate the advantages of a new
      semisynthetic glycopeptide antibiotic eremomycin pyrrolidide (5) which may be a
      prospective antimicrobial agent for further pre-clinical and clinical
      evaluations.

PMID- 30237698
TI  - Predicting medication nonadherence risk in a Chinese inflammatory rheumatic
      disease population: development and assessment of a new predictive nomogram.
AB  - Purpose: The aim of this study was to develop and internally validate a
      medication nonadherence risk nomogram in a Chinese population of patients with
      inflammatory rheumatic diseases. Patients and methods: We developed a prediction
      model based on a training dataset of 244 IRD patients, and data were collected
      from March 2016 to May 2016. Adherence was evaluated using 19-item Compliance
      Questionnaire Rheumatology. The least absolute shrinkage and selection operator
      regression model was used to optimize feature selection for the medication
      nonadherence risk model. Multivariable logistic regression analysis was applied
      to build a predicting model incorporating the feature selected in the least
      absolute shrinkage and selection operator regression model. Discrimination,
      calibration, and clinical usefulness of the predicting model were assessed using
      the C-index, calibration plot, and decision curve analysis. Internal validation
      was assessed using the bootstrapping validation. Results: Predictors contained in
      the prediction nomogram included use of glucocorticoid (GC), use of nonsteroidal
      anti-inflammatory drugs, number of medicine-related questions, education level,
      and the distance to hospital. The model displayed good discrimination with a C
      index of 0.857 (95% confidence interval: 0.807-0.907) and good calibration. High
      C-index value of 0.847 could still be reached in the interval validation.
      Decision curve analysis showed that the nonadherence nomogram was clinically
      useful when intervention was decided at the nonadherence possibility threshold of
      14%. Conclusion: This novel nonadherence nomogram incorporating the use of GC,
      the use of nonsteroidal anti-inflammatory drugs, the number of medicine-related
      questions, education level, and distance to hospital could be conveniently used
      to facilitate the individual medication nonadherence risk prediction in IRD
      patients.

PMID- 30237700
TI  - Erratum: Effectiveness of the "Elderly Activity Performance Intervention" on
      elderly patients' discharge from a short-stay unit at the emergency department: a
      quasi-experimental trial [Corrigendum].
AB  - [This corrects the article on p. 737 in vol. 13, PMID: 29731615.].

PMID- 30237699
TI  - Hidden blood loss and its risk factors after hip hemiarthroplasty for displaced
      femoral neck fractures: a cross-sectional study.
AB  - Purpose: Several authors have reported the degree of total blood loss (TBL)
      following hemiarthroplasty for displaced femoral neck fracture; however, the
      research specifically investigating on hidden blood loss (HBL) after hip
      hemiarthroplasty is still lacking. The purpose of this study is to evaluate the
      HBL in patients who underwent hip hemiarthroplasty for displaced femoral neck
      fractures and to analyze its risk factors. Patients and methods: From January
      2015 to December 2016, 212 patients (57 males and 155 females) with displaced
      femoral neck fracture undergoing hip hemiarthroplasty were included in this
      study. The demographic and relevant clinical information of the patients were
      collected. According to the Gross's formula, each patient's height, weight, and
      preoperative and postoperative hematocrit were recorded and used for calculating
      the total perioperative blood loss and HBL. Risk factors were further analyzed by
      multivariate linear regression. Results: The HBL was 525+/-217 mL, with 61.0%+/
      13.6% in the total perioperative blood loss (859+/-289 mL), and the perioperative
      hemoglobin (Hb) loss was 23.8+/-7.4 g/L. Multivariate linear regression analysis
      revealed that HBL was positively associated with higher American Society of
      Anesthesiologists (ASA) classification (regression coefficient=62.169, 95%
      CI=15.616-108.722; P=0.009), perioperative gastrointestinal bleeding/ulcer
      (regression coefficient=155.589, 95% CI=38.095-273.083; P=0.010), and transfusion
      (regression coefficient=192.118, 95% CI=135.578-248.659; P<0.001). Compared with
      females, males had a risk of increased HBL (regression coefficient=87.414, 95%
      CI=28.547-146.280; P=0.004), and general anesthesia had an increased HBL compared
      with spinal anesthesia (regression coefficient=68.920, 95% CI=11.707-126.134;
      P=0.018). Conclusion: HBL should not be ignored in patients who underwent hip
      hemiarthroplasty for displaced femoral neck fractures in the perioperative
      period, because it is a significant portion of TBL. Female patients, patients
      with higher ASA classification and perioperative gastrointestinal bleeding/ulcer,
      patients who were administered general anesthesia, or patients who underwent
      transfusion had a greater amount of HBL after hip hemiarthroplasty was performed.
      Having a correct understanding of HBL may help surgeons improve clinical
      assessment capabilities and ensure patients' safety.

PMID- 30237701
TI  - Non-cystic fibrosis bronchiectasis in the elderly: current perspectives.
AB  - Bronchiectasis is a chronic lung disease with permanently damaged airways
      predisposing to recurrent respiratory tract infections. There is an increasing
      prevalence of bronchiectasis in the elderly, affecting approximately 10 patients
      per 1,000 population. Studies have shown that older, frailer patients tend to
      have a more severe and symptomatic disease, with those aged 80 and above with
      worse quality of life, increased hospitalization and increased mortality. These
      patients will be encountered by clinicians working in all aspects of elderly
      care. This review covers the various investigations and aspects of treatment for
      bronchiectasis and how they may be utilized in a more older and generally frailer
      population.

PMID- 30237702
TI  - Possible predictive role of electrical risk score on transcatheter aortic valve
      replacement outcomes in older patients: preliminary data.
AB  - Objectives: To evaluate the predicative power of the electrical risk score (ERS),
      a noninvasive and inexpensive test obtained by means of a standard 12-lead
      electrocardiogram (ECG), in a cohort of elderly patients who had undergone
      transcatheter aortic valve replacement (TAVR). Methods: Survivors and non
      survivors after TAVR at 1-year follow-up were compared in respect to the pre
      procedural ERS as well as a number of other clinical and instrumental variables.
      ERS is composed of seven simple ECG markers: heart rate (>75 bpm); QRS duration
      (>110 ms); left ventricular hypertrophy (Sokolow-Lyon criteria); delayed QRS
      transition zone (>= V4); frontal QRS-T angle (>90 degrees ); long QTBazett (>450
      ms for men and >460 in women) or JTBazett (330 ms for men and >340 ms for women);
      and long Tpeak to Tend interval (Tp-e) (>89 ms). The trial was registered in
      ClinicalTrials.gov as NCT03145376. Results: A total of 40 patients were
      evaluated. During the follow-up, the all-cause mortality rate was 25% (ten
      patients) with 15% of cardiovascular death (six patients). The ERS was the
      strongest predictor of all-cause (odds ratio 3.73, 95% CI: 1.44-9.66, P<0.05) or
      cardiovascular (odds ratio 3.95, 95% CI: 1.09-14.27, P<0.05) mortality. Receiver
      operating characteristic curves showed that ERS had the widest significant
      sensitivity-specificity area under the curve (AUC) predicting all-cause (AUC:
      0.855, P<0.05) or cardiovascular mortality (AUC: 0.908, P<0.05). Conclusion: ERS
      seems to be a useful noninvasive tool able to stratify the risk of mortality in 1
      year follow-up of TAVR patients. These findings, however, require larger trials
      to be confirmed.

PMID- 30237703
TI  - Chronic kidney disease can increase the risk of preoperative deep vein thrombosis
      in middle-aged and elderly patients with hip fractures.
AB  - Background: Preoperative deep vein thrombosis (DVT) is a common complication in
      patients with hip fractures. Chronic kidney disease (CKD) as a frequent
      comorbidity in middle-aged and elderly patients with hip fractures is known to
      promote a proinflammatory and prothrombotic state. We aimed to identify whether
      CKD can increase the risk of DVT in middle-aged and elderly patients with hip
      fractures, as well as identify other risk factors. Patients and methods: We
      retrospectively studied 248 middle-aged and elderly patients with hip fractures
      who were admitted to our hospital from January 2016 to June 2017, meeting all the
      inclusion criteria. Doppler ultrasonography was used to diagnose DVT. Patients
      with CKD were classified into five stages according to the Kidney Diseases
      Outcomes Quality Initiative. We identified whether CKD could increase the
      occurrence of preoperative DVT in middle-aged and elderly patients with hip
      fractures and further investigated other independent risk factors for
      preoperative DVT by using univariate and multivariate analyses. Results: The mean
      estimated glomerular filtration rate was 125.7+/-41.4 mL/min/1.73 m2. Briefly,
      82.3% (n=204) had been diagnosed with normal kidney function, 11.7% (n=29) with
      mildly decreased kidney function, and 6.0% (n=15) with stage 3 and 4 CKD. In
      addition, of the 248 patients, 11.7% (n=29) developed DVT before surgery.
      Independent predictors of preoperative DVT identified by multivariate analyses
      were age, prolonged bedridden time, increased levels of fibrinogen, and lower
      estimated glomerular filtration rate. Conclusion: CKD can increase the risk rate
      of preoperative DVT in middle-aged and elderly patients with hip fractures.
      Additionally, age, prolonged bedridden time, and increased levels of fibrinogen
      were also independent risk factors for preoperative DVT in these patients. We
      should take preventive measures for these patients with risk factors in order to
      reduce the incidence of preoperative DVT.

PMID- 30237704
TI  - Antithrombotic therapies for elderly patients: handling problems originating from
      their comorbidities.
AB  - Compared with younger people, elderly people have higher risks for both
      thrombosis and bleeding. Furthermore, comorbidities frequently found in elderly
      patients complicate the management of antithrombotic therapy. Thus, when treating
      these patients, physicians often find it difficult to incorporate the principles
      of evidence-based medicine and must determine the best treatment option for each
      patient. Recently, in the fields of cerebrovascular and cardiovascular diseases,
      researchers have been rapidly accumulating new data regarding antithrombotic
      therapy, particularly in the areas of direct oral anticoagulants (DOACs) and dual
      antiplatelet therapy (DAPT). However, information related to elderly patients
      receiving antithrombotic therapy is still relatively limited. There are also more
      and more publications describing how antithrombotic therapy affects the
      pathogenesis of non-thrombotic diseases. Similarly, the number of reports
      concerning adherence to this therapy has been increasing lately. However, no
      review articles detailing these findings have yet been published. In actual
      clinical practice, antithrombotic therapy in the elderly is not a treatment
      strategy targeted to only one organ or disease. Rather, it requires an
      interdisciplinary approach aimed at maintaining the overall health of the
      patient. Thus, to assist physicians' decision-making processes for elderly
      patients, an overview of recent findings related to the evidence regarding
      concomitant medications, the secondary benefits of antithrombotic therapy for
      patients with comorbidities, and evidence regarding medication adherence is
      provided.

PMID- 30237706
TI  - Nucleosides isolated from Ophiocordyceps sinensis inhibit cigarette smoke extract
      induced inflammation via the SIRT1-nuclear factor-kappaB/p65 pathway in RAW264.7
      macrophages and in COPD mice.
AB  - Background: Ophiocordyceps sinensis (C. sinensis) extracts have been found to
      have a therapeutic effect on patients with chronic obstructive pulmonary disease
      (COPD). Silent information regulator 1 (SIRT1) plays an important role in the
      regulation of inflammatory mediators and correlates with lung function and COPD
      exacerbations. The objective of this work was to explore the anti-inflammatory
      effect and preliminary pathways of nucleosides from cultured C. sinensis on
      RAW264.7 macrophages and COPD mice. Materials and methods: The nucleosides were
      extracted from cultured C. sinensis powder and further purified by macroporous
      resin D101 and glucan G10 columns. Inflammation and oxidative stress models in
      RAW264.7 macrophages and in mice were established by injection of cigarette smoke
      extract (CSE). We then examined how the isolated nucleosides regulated the
      production of the associated inflammatory mediators in vitro and in vivo by
      enzyme-linked immunosorbent assay, reverse transcription polymerase chain
      reaction, and Western blot. Results: The nucleosides inhibited inflammatory
      mediator expression of tumor necrosis factor-alpha, interleukin-6, interleukin
      1beta, and nitric oxide in both the CSE-stimulated RAW264.7 macrophages and mice.
      Moreover, the nucleosides elevated SIRT1 activation and suppressed nuclear factor
      kappaB (NF-kappaB)/p65 activation in vitro and in vivo. Nucleoside treatment
      significantly decreased the levels of the inflammatory mediators in the
      bronchoalveolar lavage fluid (BALF) and serum of the CSE-induced mice. The
      nucleosides also altered the recruitment of inflammatory cells in BALF and
      improved characteristic features of the lungs in the CSE-induced mice.
      Conclusion: These results show that the nucleosides suppressed COPD inflammation
      through the SIRT1-NF-kappaB/p65 pathway, suggesting that the nucleosides may be
      partly responsible for the therapeutic effects of cultured C. sinensis on COPD
      patients.

PMID- 30237707
TI  - A comparative study of the five-repetition sit-to-stand test and the 30-second
      sit-to-stand test to assess exercise tolerance in COPD patients.
AB  - Purpose: The sit-to-stand test (STST) has been used to evaluate the exercise
      tolerance of patients with COPD. However, mutual comparisons to predict poor
      exercise tolerance have been hindered by the variety of STST modes used in
      previous studies, which also did not consider patients' subjective perceptions of
      different STST modes. Our aim was to compare the five-repetition sit-to-stand
      test (5STS) with the 30-second sit-to-stand test (30STS) for predicting poor
      performance in the six-minute walking test and to evaluate patients' subjective
      perceptions to determine the optimal mode for clinical practice. Patients and
      methods: Patients with stable COPD performed 5STS, 30STS and the 6MWT and then
      evaluated their feelings about the two STST modes by Borg dyspnea score and a
      questionnaire. Moreover, we collected data through the pulmonary function test,
      mMRC dyspnea score, COPD assessment test and quadriceps muscle strength (QMS). A
      receiver operating characteristic curve analysis of the 5STS and 30STS results
      was used to predict 6-minute walk distance (6MWD) <350 m. Results: The final
      analysis included 128 patients. Similar moderate correlations were observed
      between 6MWT and 5STS (r=-0.508, P<0.001) and between 6MWT and 30STS (r=0.528,
      P<0.001), and there were similar correlations between QMS and 5STS (r=-0.401,
      P<0.001) and between QMS and 30STS (r=0.398, P<0.001). The 5STS and 30STS score
      cutoffs produced sensitivity, specificity and positive and negative predictive
      values of 76.0%, 62.8%, 56.7% and 80.3% (5STS) and 62.0%, 75.0%, 62.0% and 75.0%
      (30STS), respectively, for predicting poor 6MWT performance. The 5STS exhibited
      obvious superiority in terms of the completion rate and the subjective feelings
      of the participants. Conclusion: As a primary screening test for predicting poor
      6MWD, the 5STS is similar to the 30STS in terms of sensitivity and specificity,
      but the 5STS has a better patient experience.

PMID- 30237708
TI  - Instability of nocturnal parasympathetic nerve function in patients with chronic
      lung disease with or without nocturnal desaturation.
AB  - Objective/background: This study was performed to evaluate the association of
      nocturnal autonomic nerve (AN) dysfunction, especially parasympathetic nerve (PN)
      function instability, and nocturnal oxygen desaturation (NOD) in patients with
      chronic lung diseases (CLD). Patients and methods: Twenty-nine stable CLD
      patients with irreversible pulmonary dysfunction and mild-to-moderate daytime
      hypoxemia, 13 CLD patients receiving long-term oxygen therapy (LTOT) with
      maintained SpO2 >90%, and 17 senior healthy volunteers underwent two-night
      examinations of nocturnal AN function by pulse rate variability (PRV) instead of
      heart rate variation using a photoelectrical plethysmograph simultaneously
      monitoring SpO2 and the presence of sleep disordered breathing at home. AN
      function was examined by instantaneous time-frequency analysis of PRV using a
      complex demodulation method. Results: There were no significant differences in
      mean low frequency/high frequency (HF) ratio (index of sympathetic nerve
      activity) or mean HF amplitude (index of PN activity) among controls and CLD
      patients with and without NOD (defined as SpO2 <90% for at least 3% of total
      recording time at night). However, the relative times over which the same main HF
      peak was sustained for at least 20 seconds (%HF20sec) and 5 minutes in total
      recording time, indexes of PN function stability, were significantly reduced in
      CLD patients compared with controls, and further decreased in CLD patients with
      NOD compared with non-NOD. %HF20sec was significantly higher in the LTOT group
      than the NOD group. Furthermore, PaO2 at rest and nocturnal hypoxia were
      significantly correlated with PN function instability in CLD patients.
      Conclusion: PN function is unstable at night associated with nocturnal hypoxemia
      in CLD patients, which may reflect poor quality of sleep.

PMID- 30237705
TI  - Effects of a specially designed aerobic dance routine on mild cognitive
      impairment.
AB  - Background: Mild cognitive impairment (MCI) is known as a transitional stage or
      phase between normal aging and dementia. In addition, it is associated with an
      increased risk of dementia. Research has shown that moderate-intensity exercise
      is associated with a decreased risk of cognitive impairment. Two recent studies
      demonstrated that dance interventions are associated with improved cognitive
      function in the elderly with MCI. Purpose: We evaluated the effect of a moderate
      intensity aerobic dance routine on the cognitive function in patients with MCI.
      Patients and methods: This is a single-blind randomized controlled trial. Sixty
      MCI patients were randomized to receive either treatment (aerobic dance routine +
      usual care) or control (usual care only) for 3 months. All patients received
      usual care for an additional 3 months thereafter. The aerobic dance routine was a
      specially designed dance routine which involved cognitive effort for patients to
      memorize the complex movements. Wechsler memory scale-revised logical memory (WMS
      R LM) and event-related evoked potentials (ERPs) P300 latency were used to assess
      patients' cognitive function at baseline, 3 months, and 6 months. Results: Twenty
      nine patients received exercise therapy and 31 patients received usual care.
      Patients in the treatment group showed a greater improvement in memory
      (difference in WMS-R LM changes over 3 months 4.6; 95% CI 2.2, 7.0; p<0.001) and
      processing speed (difference in P300 latency changes over 6 months -20.0; 95% CI=
      39.5, -0.4; p<0.05) compared to control. Conclusion: This dance routine improves
      cognitive function, especially episodic memory and processing speed, in MCI
      patients and merits promotion in communities.

PMID- 30237709
TI  - The role of CAT in evaluating the response to treatment of patients with AECOPD.
AB  - Background: The chronic obstructive pulmonary disease (COPD) Assessment Test
      (CAT) questionnaire is a short patient-completed questionnaire, which is used to
      assess the health status of patients with stable COPD. However, whether it is a
      good tool to evaluate the response to treatment in acute exacerbation of COPD
      (AECOPD) has been less studied. Methods: The patients were assessed at two
      visits, at admission and on the seventh day. Anthropometric variables were
      collected at admission. CAT and lung function were measured twice at the above
      time points. At the second visit, the health status of the patients were divided
      into five groups based on a 5-point Likert scale, ranging from 1 to 5, which
      represents "much better," "slightly better," "no change," "slightly worse," and
      "much worse." Responders were those who reported "much better" or "slightly
      better," and nonresponders were those who claimed "no change," "worse," or "much
      worse." Results: In total, 225 patients were recruited. The average CAT score at
      admission was 24.82+/-7.41, which declined to 17.41+/-7.35 on the seventh day.
      There were 81.33% responders, whose improvement in CAT score (9.37+/-5.24) was
      much higher than that of the nonresponders (-1.36+/-4.35). A moderate correlation
      was observed between the changes in CAT score and improvement in FEV1, FEV1%, and
      the length of hospital stay. There was a strong correlation between the changes
      in CAT score and health status. A 3.5-unit improvement in the CAT score, with
      highest area under the curve, was the cutoff to differentiate responders from
      nonresponders. Conclusion: The evolution of CAT scores during exacerbation can
      provide useful information to assess the health status of patients with AECOPD. A
      3.5-unit improvement in CAT score is the best cutoff to differentiate between
      patients who have a response or no response to treatment, which offers a
      convenient and easy way for clinicians to monitor the health status of patients
      with an AECOPD.

PMID- 30237712
TI  - Erratum: Preparation of chitin-amphipathic anion/quaternary ammonium salt
      ecofriendly dressing and its effect on wound healing in mice [Corrigendum].
AB  - [This corrects the article on p. 4157 in vol. 13, PMID: 30046240.].

PMID- 30237710
TI  - Mesenchymal stem cells loaded with paclitaxel-poly(lactic-co-glycolic acid)
      nanoparticles for glioma-targeting therapy.
AB  - Background: Mesenchymal stem cells (MSCs) possess inherent tropism towards tumor
      cells, and so have attracted increased attention as targeted-therapy vehicles for
      glioma treatment. Purpose: The objective of this study was to demonstrate the
      injection of MSCs loaded with paclitaxel (Ptx)-encapsulated poly(d,l-lactide-co
      glycolide) (PLGA) nanoparticles (NPs) for orthotopic glioma therapy in rats.
      Methods: Ptx-PLGA NP-loaded MSC was obtained by incubating MSCs with Ptx-PLGA
      NPs. The drug transfer and cytotoxicity of Ptx-PLGA NP-loaded MSC against tumor
      cells were investigated in the transwell system. Biodistribution and antitumor
      activity was evaluated in the orthotopic glioma rats after contralateral
      injection. Results: The optimal dose of MSC-loaded Ptx-PLGA NPs (1 pg/cell Ptx)
      had little effect on MSC-migration capacity, cell cycle, or multilineage
      differentiation potential. Compared with Ptx-primed MSCs, Ptx-PLGA NP-primed MSCs
      had enhanced sustained Ptx release in the form of free Ptx and Ptx NPs. Ptx
      transfer from MSCs to glioma cells could induce tumor cell death in vitro. As for
      distribution in vivo, NP-loaded fluorescent MSCs were tracked throughout the
      tumor mass for 2 days after therapeutic injection. Survival was significantly
      longer after contralateral implantation of Ptx-PLGA NP-loaded MSCs than those
      injected with Ptx-primed MSCs or Ptx-PLGA NPs alone. Conclusion: Based on timing
      and sufficient Ptx transfer from the MSCs to the tumor cells, Ptx-PLGA NP-loaded
      MSC is effective for glioma treatment. Incorporation of chemotherapeutic drug
      loaded NPs into MSCs is a promising strategy for tumor-targeted therapy.

PMID- 30237711
TI  - Synthesis of multivalent polymer-aptamer conjugates with enhanced inhibitory
      potency.
AB  - Purpose: We are interested in designing a modular strategy for creating potent
      multivalent ligands, which frequently can be used as effective inhibitors of
      undesired biomolecular interactions. For example, such inhibitors might prevent
      the self-assembly of bacterial toxins or the attachment of a virus to its host
      cell receptors. Methods: We used a biocompatible polyamino acid polymer as a
      scaffold for grafting multiple copies of an oligonucleotide aptamer (OA).
      Specifically, the carboxylates on the side chains of polyglutamic acid (PGA) were
      modified with a thiol-reactive linker, N-aminoethyl maleimide (AEM), and thiol
      functionalized OAs were attached to the maleimide moieties. The resulting
      conjugates were tested for their ability to compete with and inhibit the binding
      of unconjugated monovalent OAs to the target cell receptor. Results: Multivalent
      PGA-OA conjugates with low, medium, and high valency were successfully prepared.
      The varying valency and successful purification to remove unconjugated OAs were
      confirmed by polyacrylamide gel electrophoresis. The resulting purified
      conjugates inhibited the binding of unconjugated monovalent OAs, and the measured
      half maximal inhibitory concentration (IC50) values corresponded to a 38-88-fold
      enhancement of potency on a per-aptamer basis, relative to OA alone. Conclusion:
      Multivalent conjugation of OA ligands has potential as a generally useful way to
      improve the potency of the interaction between the ligand and its target
      receptor. We have demonstrated this principle with a known OA as a proof of
      concept as well a synthetic strategy that can be used to synthesize multivalent
      conjugates of other OAs.

PMID- 30237713
TI  - A novel bacterial cellulose membrane immobilized with human umbilical cord
      mesenchymal stem cells-derived exosome prevents epidural fibrosis.
AB  - Introduction: Failed back surgery syndrome is a situation where there is failure
      after lumbar surgery aimed at correcting lumbar disease that is characterized by
      continuous back and/or leg pain. Epidural fibrosis and adhesions are among the
      major causes of failed back surgery syndrome. In recent years, several
      biomaterials have been applied as barriers or deterrents to prevent the
      compression of neural structures by postsurgical fibrosis. Methods: In this
      study, a new bacterial cellulose (BC) anti-adhesion membrane, composed of
      exosomes from human umbilical cord mesenchymal stem cells, was developed. Its
      structure and morphology, water content, thickness, and mechanical properties of
      elasticity were analyzed and characterized. The degradation of the BC+exosomes
      (BC+Exos) membrane in vitro was evaluated, and its in vitro cytotoxicity and in
      vivo biocompatibility were tested. The prevention effect of BC+Exos membrane on
      epidural fibrosis post-laminectomy in a rabbit model was investigated. Results:
      The BC+Exos membrane showed a three-dimensional network structure constituted of
      high-purity cellulose and moderate mechanical properties. No degeneration was
      observed. The BC+Exos membrane showed no cytotoxicity and displayed
      biocompatibility in vivo. The BC+Exos film was able to inhibit epidural fibrosis
      and peridural adhesions. Conclusion: Based on the current findings, the BC+Exos
      membrane is a promising material to prevent postoperative epidural fibrosis and
      adhesion.

PMID- 30237714
TI  - The effects of amine-modified single-walled carbon nanotubes on the mouse
      microbiota.
AB  - Background: Amine-modified carbon nanotubes are drug delivery platforms with
      great potential that have not yet been applied in human clinical trials. Although
      modified nanotube vectors have the ability to carry multiple effectors, targeting
      agents, and even wrapped RNA, reports on unmodified, insoluble carbon nanotubes
      have highlighted inflammation in organs, including the intestine, with disruption
      of its resident microbiota. Disruption of the microbiota may allow for
      colonization by pathogenic bacteria, such as Clostridoidies difficile, stimulate
      immunoinfiltrates into the lamina propria or alter the absorption of
      therapeutics. Most proposed nanotube drugs are soluble, modified structures that
      are administered parenterally, and the majority of these soluble macromolecules
      are renally excreted; however, some are released into the bile, gaining access to
      the gastrointestinal tract. Methods: Using environmentally isolated BALB/C mice
      in oral and intraperitoneal dosing models, high dose (3.80 or 4.25 mg/week), we
      administered amine-modified, soluble carbon nanotubes for 7 or 8 weeks. The
      general health and weight of the mice were monitored weekly, and upon killing,
      the diversity and content of their colonic, cecal, and ileal microbiota were
      assessed using shotgun 16S DNA sequencing. Results and conclusion: We show that
      while oral administration at suprapharmacological doses modestly altered the
      alpha- and beta-diversity of the mouse microbiome, these changes did not result
      in observed changes in clinical end points. Intraperitoneally-dosed mice
      exhibited none of the toxicities assessed.

PMID- 30237716
TI  - A randomized controlled trial of mindfulness-based Tai Chi Chuan for subthreshold
      depression adolescents.
AB  - Purpose: The incidence of subthreshold depression (StD) in adolescents is growing
      rapidly, which in turn is known to impair functioning and increase the risk of
      major depression. It is therefore important to provide effective intervention to
      prevent the transition from StD to major depression. As a traditional Chinese
      mind-body exercise, Tai Chi Chuan (TCC) may be an available selection.
      Researchers have shown the effectiveness of mindfulness-based therapy on
      depression; however, for the StD youth, there have been no studies to investigate
      whether mindfulness-based Tai Chi Chuan (MTCC) can be recommended as an effective
      exercise for improving their psychological state. The aim of present study was to
      evaluate the effect of MTCC on psychological outcomes of StD adolescents
      including the depression levels and mindfulness state in a randomized controlled
      trial (RCT). Patients and methods: An RCT was carried out. A sample of 64
      participants who meet the inclusion criteria agreed to be arranged randomly to
      either the MTCC group (n=32) or the control group (n=32). Participants of the
      MTCC group received an 8-week, 2 days per week, 90-minute MTCC intervention for
      each session. Usual physical curriculum was administered to the participants in
      the control group. The effectiveness of MTCC training was measured by blinded
      evaluators through validated scales, which included depressive symptoms, stress,
      and mindfulness level before and after the intervention. Results: Significant
      improvements in psychological health were observed from MTCC groups. After 8-week
      intervention, superior outcomes were also observed for MTCC when compared with
      control group for decrease in depression (F=59.482, P<0.001) and stress level
      (F=59.482, P<0.001) and increase in mindfulness (F=59.482, P<0.001). Conclusion:
      The findings of this preliminary study indicated the effects of the MTCC
      intervention on depression level among StD youngsters. This study provides
      preliminary evidence that MTCC is suitable for Chinese adolescents and is
      effective in decreasing depression level.

PMID- 30237717
TI  - Ertugliflozin: a sodium-glucose cotransporter-2 (SGLT-2) inhibitor for glycemic
      control in type 2 diabetes.
AB  - Recently, a new class of anti-diabetic drugs has found its way into the market:
      sodium-glucose cotransporters (SGLT) inhibitors. Two major SGLT isoforms have
      been identified: SGLT-2, mainly expressed in proximal renal tubules, and SGLT-1,
      mainly expressed in the small intestine, the proximal renal tubule, and the
      myocardium. SGLT-2 inhibitors increase urinary glucose excretion, lowering
      glycemia without inducing excessive insulin secretion. Marketed SGLT-2 inhibitors
      actually include dapagliflozin, canagliflozin, and empagliflozin; a new SGLT-2
      inhibitor is being studied: ertugliflozin. Ertugliflozin is a potent inhibitor of
      SGLT-2 and possesses a high selectivity over glucose transport via SGLT-1 and
      several other glucose transporters GLUT-1-4. Ertugliflozin inhibits renal glucose
      reabsorption resulting in urinary glucose excretion and thereby reduces plasma
      glucose and glycated hemoglobin in subjects with type 2 diabetes mellitus.
      Ertugliflozin is being developed as an adjunct to diet and exercise to improve
      glycemic control in patients with type 2 diabetes mellitus. The aim of this
      review is to evaluate the preliminary published data about this new molecule.

PMID- 30237715
TI  - Electrospun PCL/mupirocin and chitosan/lidocaine hydrochloride multifunctional
      double layer nanofibrous scaffolds for wound dressing applications.
AB  - Background: An ideal wound dressing should exhibit good biocompatibility,
      minimize pain and infection, absorb excess exudates, and maintain a moist
      environment. However, few clinical products meet all these needs. Therefore, the
      aim of this study was to fabricate a multifunctional double layer nanofibrous
      scaffolds (DLS) as a potential material for wound dressing. Materials and
      methods: The scaffold was formed from mupirocin and lidocaine hydrochloride
      homogeneously incorporated into polycaprolactone as the first layer of scaffolds
      and chitosan as the second layer of scaffolds nanofibers through electrospinning.
      The fabricated nanofibrous scaffolds were characterized by scanning electron
      microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis,
      differential scanning calorimetry, and measurement of swelling ratio, contact
      angle, drug release, and mechanical properties. Furthermore, antibacterial
      assessment, live/dead cell assays, and MTT assays were used to investigate the
      antibacterial activity and cytotoxicity of the nanofibrous scaffolds. Results:
      The morphology of the nanofibrous scaffolds was studied by scanning electron
      microscopy, showing successful nanofibrous scaffolds. Fourier transform infrared
      spectroscopy demonstrated the successful incorporation of the material used to
      produce the produced nanofibrous scaffolds. Thermal studies with
      thermogravimetric analysis and differential scanning calorimetry indicated that
      the DLS had high thermal stability. The DLS also showed good in vitro
      characteristics in terms of improved swelling ratio and contact angle. The
      mechanical results revealed that the DLS had an improved tensile strength of 3.88
      MPa compared with the second layer of scaffold (2.81 MPa). The release of drugs
      from the scaffold showed different profiles for the two drugs. Lidocaine
      hydrochlo ride exhibited an initial burst release (66% release within an hour);
      however, mupirocin exhibited only a 5% release. Furthermore, the DLS nanofibers
      displayed highly effective antibacterial activities against Staphylococcus
      aureus, Escherichia coli, and Pseudomonas aeruginosa and were nontoxic to
      fibroblasts. Conclusion: The fabricated DLS exhibited excellent hydrophilicity,
      cytocompatibility, sustained drug release, and antibacterial activity, which are
      favorable qualities for its use as a multifunctional material for wound dressing
      applications.

PMID- 30237718
TI  - New-onset of postoperative atrial fibrillation is likely to recur in the absence
      of other triggers.
AB  - Background: Incident atrial fibrillation (AF) is reported in 10%-65% of patients
      without previous AF diagnosis after open heart surgery. The risk of late AF
      recurrence after a postoperative AF onset is unclear, and it is controversial
      whether AF limited to the postoperative period should elicit oral anticoagulation
      (OAC) therapy. The primary objective of this study was to evaluate the long-term
      recurrence of AF in patients developing new-onset peri-procedural AF. Patients
      and methods: Patients (n=189) with available baseline and follow-up data included
      in Left Atrial Appendage Closure with Surgery trial were coded for known AF at
      baseline and for postoperative first-time AF diagnosis. AF occurrence was
      classified as follows: peri-procedural <=7 days postoperatively, early >7 days
      but <=3 months and late >3 months. Patients with no AF recurrence registered
      during follow-up were invited to undergo Holter monitoring. Results: A total of
      163 (86.2%) patients had no history of AF. Among these, 80 (49.1%) developed new
      onset peri-procedural AF. After a mean follow-up of 3.7+/-1.6 years, late AF
      occurred in 35 of the 80 (43.8%) patients who developed peri-procedural AF and in
      6 additional patients (7.2%) who remained in sinus rhythm until discharge (hazard
      ratio [HR] 9.3, 95% CI 3.8-22.4, p<0.001). Patients with peri-procedural AF and
      early AF had 12.24 times higher risk of late AF (95% CI 4.76-31.45, p<0.001) as
      compared to the group with no postoperative AF. Conclusion: New-onset of AF after
      open heart surgery has a high rate of recurrence and should not be regarded as a
      self-limiting phenomenon secondary to surgery.

PMID- 30237719
TI  - What is known about deferasirox chelation therapy in pediatric HSCT recipients:
      two case reports of metabolic acidosis.
AB  - To date, in pediatric field, various hematological malignancies are increasingly
      treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Iron
      overload and systemic siderosis often occur in this particular cohort of patients
      and are associated with poor prognosis. We describe herein the case of two allo
      HSCT patients, on treatment with deferasirox; they showed histopathological
      elements compatible with venoocclusive disease or vanishing bile duct syndrome in
      ductopenic evolution before deferasirox started. The first patient developed drug
      induced liver damage with metabolic acidosis and the second one a liver
      impairment with Fanconi syndrome. After withdrawing deferasirox treatment, both
      patients showed improvement. Measurements of drug plasma concentrations were
      performed by HPLC assay. The reduction and consequent disappearance of symptoms
      after the suspension of deferasirox substantiate its role in inducing hepatic
      damage, probably enabling the diagnosis of drug-induced liver damage. But the
      difficulties in diagnosing drug-related toxicity must be underlined, especially
      in compromised subjects. For these reasons, in patients requiring iron-chelating
      therapy, close and careful drug therapeutic monitoring is strongly recommended.

PMID- 30237720
TI  - A case of probable oxybutynin-induced increase in liver enzymes.
AB  - We describe the case of a 49-year-old male who presented to the emergency
      department with right-sided weakness and inability to speak. He was diagnosed
      with stroke and was admitted to Qatar Rehabilitation Institute after he was
      treated for the acute phase at Hamad General Hospital. As part of his management,
      he was started on oxybutynin 5 mg orally twice daily for the treatment of
      overactive bladder. Within a week, his liver enzymes started to increase. After a
      thorough medication review, oxybutynin was suspended as it was the only suspected
      medication to be responsible of this elevation in liver enzymes. When Naranjo
      Adverse Drug Reaction Probability Scale was used to assess the probability of an
      adverse drug reaction (ADR), a score of 6 was obtained indicating a "Probable"
      ADR. In conclusion, this is the first published report of oxybutynin-induced
      elevation in liver enzymes. Further reports are required to highlight this
      probable ADR and alert all health professionals about it.

PMID- 30237721
TI  - An unusual successful treatment with non-sulfonamides: primary cutaneous
      nocardiosis caused by Nocardia brasiliensis.
AB  - Introduction: Primary cutaneous nocardiosis is a rare suppurative or
      granulomatous inflammation disease caused by Nocardia infection. Because of
      nonspecific clinical findings, it is always misdiagnosed as common pyogenic
      infection. Sulfonamides have been the standard treatment for nocardiosis, but the
      outcome is always poor due to the high rates of misdiagnosis and refractoriness
      of the disease. Cases presentations: The presented cases are patients of acute
      suppurative cutaneous infection without involvement of other organs. We report
      four cases, of which two cases were localized cutaneous nocardiosis and the other
      two were lymphocutaneous type of nocardiosis. All cases were diagnosed with pus
      culture which turned out to be Nocardia brasiliensis. We report an improvement of
      primary cutaneous nocardiosis symptoms in the four patients treated with non
      sulfonamides. All patients were cured and recovered without recurrence during
      follow-up. Conclusion: Our results suggest that non-sulfonamides are effective
      treatment for the patients with primary cutaneous nocardiosis who are resistant
      or intolerant to sulfonamides.

PMID- 30237723
TI  - Hsa_circ_0003998 promotes cell proliferation and invasion by targeting miR-326 in
      non-small cell lung cancer.
AB  - Background: Circular RNAs represent a new class of noncoding RNAs involved in the
      development of cancer. However, little is known about their role in non-small
      cell lung cancer (NSCLC). Methods: We examined hsa_circ_0003998 levels in 60
      NSCLC tissues by quantitative real-time polymerase chain reaction and analyzed
      the clinicopathologic significance of hsa_circ_0003998 expression. The effect of
      small interfering RNA-mediated hsa_circ_0003998 knockdown on proliferation and
      invasion was analyzed in A549 and H1299 cells in vitro. Moreover, the target
      genes of hsa_circ_0003998 were further explored by bioinformatic analysis, dual
      luciferase reporter assays, and rescue experiments. Results: Hsa_circ_0003998
      upregulation was associated with larger tumor size and lymph node metastasis and
      also correlated with shorter overall survival of NSCLC patients. Functional
      experiments showed knockdown of hsa_circ_0003998 restrained cell proliferation
      and invasion in NSCLC cells. In particular, hsa_circ_0003998 upregulated the
      expression of miR-326 target gene Notch1 through sponging miR-326. Furthermore,
      the tumor-inhibiting effect of hsa_circ_0003998 silencing was blocked by miR-326
      inhibitor. Conclusion: hsa_circ_0003998/miR-326/Notch1 pathway regulates the
      progression of NSCLC.

PMID- 30237722
TI  - Arterial elasticity as a risk factor for early cardiovascular disease among
      testicular cancer survivors treated with platinum-based chemotherapy: a cross
      sectional pilot study.
AB  - Purpose: Testicular cancer survivors who have received platinum-based
      chemotherapy are at risk for premature cardiovascular disease. The etiology of
      this risk is not well understood. This pilot study explores the impact of
      platinum-based chemotherapy on endothelial function. Methods: Testicular cancer
      survivors <30 years old at the time of diagnosis who received platinum-based
      chemotherapy between 2002 and 2012, as well as 17 similarly aged male controls,
      were identified. Consented subjects underwent vascular assessment using the
      HDI/PulseWave CR-2000 Cardiovascular Profiling System and the Endo-PAT2000
      system. Biomarkers and functional test markers were compared among cases,
      controls, and a group of historical controls using two sided two-sampled t-tests
      and Wilcoxon rank-sum tests. Results: Thirteen survivors with a median age of
      30.2 years and body mass index of 27.3 were enrolled, along with 17 healthy
      controls with a median age of 27.1 years and body mass index of 24.8. Median time
      from chemotherapy was 4.7 (range: 0.8-14) years. There was no statistical
      difference in reactive hyperemia peripheral arterial tonometry ratio between
      cases and controls (p = 0.574). There was no statistical difference in small or
      large artery elasticity between cases and controls (p = 0.086) or between cases
      and historical controls (p = 0.729). There was also no statistical difference in
      the blood levels of circulating endothelial cells, von Willebrand factor, and
      vascular cell adhesion molecules. There was a trend toward increased metabolic
      syndrome in cases (15%) as compared to recruited controls (6%), though this
      difference was not statistically significant (p = 0.565). Conclusion: Testicular
      cancer survivors have no clinically significant difference in endothelial
      function compared to controls 4 years after the completion of chemotherapy.
      Further research is needed to explore the secondary modifiable causes that may
      contribute to the risk of premature cardiovascular disease.

PMID- 30237724
TI  - RRM1 expression and the clinicopathological characteristics of patients with non
      small cell lung cancer treated with gemcitabine.
AB  - Background: The usefulness of ribonucleotide reductase catalytic subunit M1
      (RRM1) for predicting the therapeutic effects of gemcitabine-containing
      chemotherapy in patients with non-small cell lung cancer (NSCLC) remains
      controversial. RRM1-positive patients show unique clinicopathological features.
      Methods: Here, we performed a meta-analysis to systematically evaluate the
      relationship between RRM1 expression and the clinicopathological characteristics
      of NSCLC patients treated with gemcitabine-containing regimens. A comprehensive
      electronic and manual search was performed to identify relevant articles. The
      pooled relative risk (RR) and 95% CI were used to estimate the relation between
      the clinicopathological characteristics of NSCLC patients and RRM1 expression.
      Results: The study included 31 observational studies and 3,667 patients. The
      analysis showed no significant association between RRM1 expression and
      pathological type, stage, and smoking status; however, RRM1 positivity was
      significantly lower in women than in men (43.0% vs 51.7%, RR=0.84, 95% CI: 0.74
      0.94, P=0.004). Conclusion: The present pooled analyses demonstrated that RRM1
      positivity in women with advanced NSCLC was associated with a higher rate of
      response to gemcitabine-containing regimens. Immunohistochemistry may be valuable
      to prescreen for RRM1 expression in clinical practice, whereas PCR can be
      routinely used as a verification method. These findings will help design suitable
      molecular-targeted therapies for NSCLC.

PMID- 30237725
TI  - Preoperative high-sensitivity C-reactive protein to lymphocyte ratio index plays
      a vital role in the prognosis of hepatocellular carcinoma after surgical
      resection.
AB  - Background: At present, the predictive ability of the prognostic indicator of
      hepatocellular carcinoma (HCC) is still limited. This study aims to analyze the
      relationship between the preoperative high-sensitivity C-reactive protein to
      lymphocyte ratio (HCLR) and the clinicopathologic characteristics of HCC.
      Patients and methods: A total of 229 HCC patients undergoing surgical resection
      were retrospectively analyzed. The majority of the patients (132/229) had tumors
      larger than 5 cm, and 45 out of 229 had more than one tumor focus. Receiver
      operating characteristic curve analysis was used to decide the cutoff value of
      HCLR. The overall survival (OS) and progression-free survival (PFS) rates were
      evaluated by adopting the Kaplan-Meier method. Results: The cutoff value of HCLR
      for the best discrimination of HCC prognosis was 1.3 with a sensitivity of 75.5%
      and a specificity of 71.8%. The area under the receiver operating characteristic
      curve was 0.791 (95% CI, 0.731-0.840). Preoperative HCLR at a high level (>1.3)
      was positively correlated with large tumor size, TNM stage, microvascular
      invasion, and recurrence. The mean OS and PFS in patients with HCLR >1.3 were
      significantly shorter than in those with HCLR <=1.3. Univariate and multivariate
      analyses revealed the HCLR was an independent predictor of OS and PFS.
      Conclusion: HCLR was an important independent predictor of dismal prognosis in
      HCC patients and can be used as a sensitive indicator for the dynamic monitoring
      of postoperative patients.

PMID- 30237726
TI  - Pembrolizumab and salvage chemotherapy in EGFR T790M-positive non-small-cell lung
      cancer with high PD-L1 expression.
AB  - Immuno-checkpoint inhibitors (ICI) have become an effective treatment option for
      non-small-cell lung cancer patients. However, ICI therapy was reported to be less
      effective in patients with epidermal growth factor receptor (EGFR) mutations than
      in those with wild-type EGFR. We report here that an non-small-cell lung cancer
      patient with the EGFR mutant T790M showed a programmed cell death ligand 1 (PD
      L1) expression level that increased from <25% to >90% after eighth-line
      osimertinib therapy. He was treated with pembrolizumab as a ninth-line treatment,
      and attained stable disease. After the pembrolizumab therapy, he was treated with
      gemcitabine, which produced a good response despite being the 10th-line
      treatment. We should consider administering ICI and chemotherapy even to EGFR
      mutant patients after failure of EGFR tyrosine kinase inhibitor, especially in
      cases with high PD-LI expression.

PMID- 30237727
TI  - Better drugs for Lyme disease: focus on the spirochete.
AB  - Twenty-five years ago, the AIDS epidemic was wreaking havoc around the world.
      Although "HIV denialists" threatened to undermine research efforts to combat the
      epidemic, development of targeted antiviral therapy eventually provided effective
      treatment for the disease. Now the Lyme disease epidemic is wreaking havoc around
      the world, and "Lyme denialists" are undermining efforts to combat the epidemic.
      Drawing on our experience with the AIDS epidemic, there is a significant need to
      develop targeted therapy to control the Lyme disease epidemic.

PMID- 30237728
TI  - Appropriate composites of cefoperazone-sulbactam against multidrug-resistant
      organisms.
AB  - Objectives: This study aims to assess the in vitro activity of different
      cefoperazone-sulbactam ratios against different multidrug-resistant organisms
      (MDROs). Materials and methods: Minimum inhibitory concentrations (MICs) and
      susceptibility rates of cefoperazone, sulbactam and cefoperazone-sulbactam at
      fixed ratios of 2:1, 1:1 and 1:2 against 344 MDRO clinical isolates, including
      extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (n=58), ESBL
      producing Klebsiella pneumoniae (n=58), carbapenem-resistant Enterobacteriaceae
      (n=57), carbapenem-resistant Pseudomonas aeruginosa (n=49) and carbapenem
      resistant Acinetobacter baumannii (n=122), were measured. Results: Combined
      treatment with sulbactam and cefoperazone resulted in decreased MIC50 values
      across all MDROs, as well as decreases in most MIC90 values, except for
      carbapenem-resistant Enterobacteriaceae and carbapenem-resistant P. aeruginosa
      (MIC90 values remained >64 mg/L). Susceptibility rates of treatment with
      cefoperazone alone against all MDROs were much lower than that of cefoperazone
      sulbactam combination (all P<0.05), except in carbapenem-resistant P. aeruginosa.
      Additionally, the susceptibility rate gradually increased as the ratio of
      cefoperazone-sulbactam was adjusted from 2:1 to 1:1 and to 1:2 for carbapenem
      resistant Enterobacteriaceae, ESBL-producing K. pneumoniae and carbapenem
      resistant A. baumannii. There were no significant ratio-dependent changes in
      susceptibility rates with cefoperazone-sulbactam in carbapenem-resistant P.
      aeruginosa. Conclusion: Adding sulbactam enhances cefoperazone activity against
      most MDROs excluding carbapenem-resistant P. aeruginosa, and the activity of
      cefoperazone-sulbactam against these MDROs is greatest at a ratio of 1:2,
      followed by ratios of 1:1 and 2:1.

PMID- 30237729
TI  - Comparative evaluation between two nutritional supplements in the improvement of
      telogen effluvium.
AB  - Purpose: Telogen effluvium (TE) is defined as a diffuse hair loss characterized
      by shortening of the anagen phase and precipitation of the telogen phase, with a
      consequent reduction of total hair volume. Nutritional supplementation is
      indicated under conditions in which TE is related to dietary disorders. The aim
      of this clinical study was to compare the efficacy of two different supplements
      in monotherapy for TE. Patients and methods: Female adult patients were
      randomized to receive two oral nutritional supplements (group 1: a supplement
      composed of zinc, biotin, iron, vitamins A, C, E, and B complex, folic acid,
      magnesium, and amino acids of keratin and collagen and group 2: calcium
      pantothenate cystine, thiamine nitrate, medicinal yeast, keratin, and
      aminobenzoic acid) to treat hair loss for 180 days. They were evaluated
      clinically and by digital trichoscopy. Results: Clinical evaluation showed
      significant clinical improvement (P<0.05) for the evaluated parameters: hair
      loss, hair volume, density of hair (scalp cover), hair shine, hair strength, in
      180 days. At 90 days evaluation, group 1 showed significant improvement for all
      parameters, while group 2 did not show any significant improvement for hair shine
      and hair strength. In the digital trichoscopy, there was a significant
      improvement only in group 1 (11.09%*7.76%) after 180 days. Conclusion: In
      idiopathic TE, the nutritional component should be suspected; the supplementation
      of an association of nutrients in recommended daily intake can lead to
      significant improvement of the condition from the first trimester of use. The use
      of an association with proven efficacy and a safety profile and posologic
      convenience facilitate its indication and patient adherence.

PMID- 30237730
TI  - Sacroiliitis - early diagnosis is key.
AB  - Sacroiliitis, inflammation of the sacroiliac joint (SIJ), may be associated with
      many rheumatic and nonrheumatic disorders. The diagnosis of sacroiliitis may be
      difficult in many patients, and awareness of its typical manifestations along
      with recognition of its diverse presentations and cognizance of the limitations
      of today's imaging modalities are critical to good clinical practice. This review
      presents the didactic approach to the early diagnosis of sacroiliitis in patients
      with suspected axial spondyloarthritis and other nosologic entities, discussing
      also differential interpretation of information acquired from patients'
      histories, physical examination, and imaging.

PMID- 30237731
TI  - High glucose induces a priming effect in macrophages and exacerbates the
      production of pro-inflammatory cytokines after a challenge.
AB  - Introduction: Painful diabetic neuropathy is associated with chronic
      inflammation, in which macrophages are the key effectors. We utilized an in vitro
      approach to determine the effects of high glucose on macrophage phenotype.
      Materials and methods: We exposed human THP-1 macrophages to normal glucose (5
      mM) and a clinically relevant high glucose environment (15 mM) and measured the
      expression and concentration of molecules associated with a diabetic cellular
      phenotype. Results: We found that THP-1 macrophages in high glucose conditions
      did not influence the basal expression of cyclooxygenase-2, Toll-like receptor-4,
      or class A scavenger receptor mRNA, or the concentrations of the cytokines
      interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and IL-10, but
      induced a priming effect on tumor necrosis factor (TNF)-alpha. Then, we
      stimulated THP-1 macrophages with a strong pro-inflammatory stimulus
      lipopolysaccharide (LPS; 5 ug/mL). After stimulation with LPS, we observed an
      exacerbated increase in TNF-alpha, IL-6, and MCP-1 concentration in the high
      glucose condition compared to the normal glucose environment. THP-1 macrophages
      in high glucose conditions developed tolerance to IL-10 anti-inflammatory effects
      (TNF-alpha production) when challenged with LPS. Conclusion: Our in vitro
      approach allows the study of macrophages as potential targets for therapeutic
      purposes since it compares them to primary human macrophages exposed to high
      glucose and macrophages from patients with diabetes or complications of painful
      diabetic neuropathy (i.e. ulcers, adipocytes, and pancreas).

PMID- 30237733
TI  - Sexual life satisfaction of methadone-maintained Chinese patients: individuals
      with pain are dissatisfied with their sex lives.
AB  - Purpose: Pain is potentially associated with sexual dysfunction. Both sexual
      dysfunction and pain are common in methadone-maintained patients, but the
      association of pain with sexual dysfunction in methadone-maintained patients is
      rarely studied. This study examined the association between pain and sexual life
      satisfaction (SLS) in Chinese patients receiving methadone maintenance treatment
      (MMT). Patients and methods: A total of 477 methadone-maintained patients who
      recently had sex with their sex partners were recruited from three MMT clinics in
      Wuhan, China. SLS was assessed with a single question, and the sociodemographic,
      psychological, and clinical data were collected with standardized questionnaires.
      Pain intensity was assessed with the 5-point verbal rating scale. Multiple
      ordinary logistic regression was used to control for potential confounders that
      may bias the pain-SLS relationship. Results: The prevalence of self-reported
      dissatisfaction with one's sexual life was significantly higher in patients with
      clinically significant pain (CSP) than those without CSP (41.5% vs 19.4%, chi2
      =23.567, P<0.001). After controlling for potential sociodemographic,
      psychological, and clinical confounders, CSP was still significantly and
      independently associated with an increase in sexual life dissatisfaction (OR
      =1.89, P=0.011). Conclusion: Pain is significantly associated with low SLS in
      methadone-maintained patients. Appropriate pain management might improve SLS of
      patients receiving MMT.

PMID- 30237732
TI  - Health care utilization by veterans prescribed chronic opioids.
AB  - Purpose: Ambulatory resources such as telephone calls, secure messages, nurse
      visits, and telephone triage are vital to the management of patients on chronic
      opioid therapy (COT). They are also often overlooked as health care services and
      yet to be broadly studied. The aim of the present study was to describe the
      Veterans Affairs (VA) health care utilization by patients based on COT, type, and
      amount of opioids prescribed. Patients and methods: A retrospective chart review
      was done on 617 patients on COT at a VA primary care clinic. Instances of health
      care utilization (emergency department visits [EDVs], hospitalizations, clinic
      visits, telephone triage calls, telephone calls/secure messages/nurse visits)
      were obtained. Results: Patients were likely to have more telephone calls, secure
      messages, or nurse visits if they were prescribed a schedule II opioid or if they
      were on more than one opioid. Model-based results found that patients on COT were
      more likely to have EDVs, telephone triage calls, and clinic contact compared to
      patients who were not on chronic opioids. Conclusion: The results are despite
      having a Patient Aligned Care Team, which is the VA's patient-centered medical
      home. This suggests that reducing health care utilization for patients on COT may
      not be possible with just a primary care involvement.

PMID- 30237734
TI  - Clinical characteristics of patients with posterosuperior labral tear: a
      comparison with patients with other shoulder disorders.
AB  - Background: Among the various causes of shoulder pain, the glenoid labral tear is
      likely to be overlooked due to its ambiguous symptoms, especially if clinicians
      do not have a prior suspicion, making it difficult to diagnose, unlike adhesive
      capsulitis or a rotator cuff tear. Therefore, the aim of this study was to
      evaluate the clinical features of posterosuperior (PS) labral tear. Methods: Of
      the patients who visited the clinic, the medical records of patients with
      shoulder pain who underwent shoulder magnetic resonance imaging or ultrasound
      after intra-articular injection (arthrosonography) were investigated
      retrospectively. Based on these criteria, a total of 120 patients with adhesive
      capsulitis, rotator cuff problem, or PS labral tear were included for analysis in
      this study. Results: In the physical examination, all patients with a PS labral
      tear were positive on the O'Brien test (13/13, 100%) and the external rotation
      (ER) test with the upper arm in the abduction position (abduction and ER [ABER]
      test) (13/13, 100%), but they were negative on other tests, such as the Hawkins
      Kennedy (1/13, 7.69%) and Neer (0/13, 0.00%) tests. Except one patient, all
      patients with a PS labral tear were negative on the ER test with the upper arm in
      the neutral position (ER test) (1/13, 7.69%). In the clinical history, all
      patients with a PS labral tear had a characteristic episode of shoulder pain
      occurring in the excessive ABER posture. Conclusion: In patients with
      characteristic physical findings (no definite loss of motion of the shoulder
      joint, negative in an ER test, but positive in an ABER test and O'Brien test),
      and with a clinical history of PS labral tear (a history of pain occurring with
      the excessive ABER posture), clinicians need to have a suspicion of PS labral
      tear and to identify the PS labral tear using MRI or arthrosonography.

PMID- 30237735
TI  - Anticancer and cardio-protective effects of liposomal doxorubicin in the
      treatment of breast cancer.
AB  - Breast cancer (BC) is a highly prevalent disease, accounting for the second
      highest number of cancer-related mortalities worldwide. The anthracycline
      doxorubicin (DOX), isolated from Streptomyces peucetius var. caesius, is a potent
      chemotherapeutic drug that is successfully used to treat various forms of liquid
      and solid tumors and is currently approved to treat BC. DOX exerts its effects by
      intercalation into DNA and inhibition of topoisomerases I and II, causing damage
      to DNA and the formation of reactive oxygen species (ROS), resulting in the
      activation of caspases, which ultimately leads to apoptosis. Unfortunately, DOX
      also can cause cardiotoxicity, with patients only allowed a cumulative lifetime
      dose of 550 mg/m2. Efforts to decrease cardiotoxicity and to increase the blood
      circulation time of DOX led to the US Food and Drug Administration (FDA) approval
      of a PEGylated liposomal formulation (L-DOX), Doxil(r) (known internationally as
      Caelyx(r)). Both exhibit better cardiovascular safety profiles; however, they are
      not currently FDA approved for the treatment of metastatic BC. Here, we provide
      detailed insights into the mechanism of action of L-DOX and its most common side
      effects and highlight results of its use in clinical trials for the treatment of
      BC as single agent and in combination with other commonly used chemotherapeutics.

PMID- 30237736
TI  - Significance of circulating tumor cells in osteosarcoma patients treated by
      neoadjuvant chemotherapy and surgery.
AB  - Purpose: By examining and identifying circulating tumor cell (CTC) counts and
      subtypes of peripheral blood in osteosarcoma patients, we evaluated the
      relationship between CTCs and characteristics of osteosarcoma patients, as well
      as CTC changes after neoadjuvant chemotherapy and surgery. Methods: CanPatrolTM
      CTC technology was used to detect CTCs in peripheral blood before and after
      treatment in 32 osteosarcoma patients. Peripheral blood samples from 10 healthy
      volunteers were included as controls and examined for the presence of CTCs.
      Results: Of the 32 osteosarcoma patients, CTCs were detected in 30 patients
      before treatment, and the average CTC count was 14.06+/-9.08. No CTCs were
      detected in the 10 healthy volunteers. The detected CTCs were divided into
      epithelial CTCs, mesenchymal CTCs (M-CTCs), and biophenotypic
      epithelial/mesenchymal CTCs. The average number of pretreatment CTCs was higher
      in stage III patients than in stage IIB patients (P=0.012). Twenty-eight patients
      were screened for changes in CTC count at 1 week after neoadjuvant chemotherapy
      and at 4 weeks after surgery. We divided these 28 patients into two groups
      according to the changes in the percentage of M-CTCs before and after treatment,
      and the results showed that the disease-free survival (DFS) was significantly
      shorter in the M-CTC percentage-increased group than in the M-CTC percentage
      decreased or no-change group (P=0.032). Five patients with stage II osteosarcoma
      were examined for CTCs at the appearance of lung metastases, and the total number
      of CTCs was found to be higher at the appearance of lung metastases than before
      treatment in these patients. Conclusion: The rate of presence of CTCs in the
      peripheral blood of osteosarcoma patients is high, and patients with an increased
      percentage of M-CTCs after treatment have a shorter DFS. The dynamic monitoring
      of changes in CTC counts after treatment has clinical significance for the timely
      detection of recurrence or metastasis.

PMID- 30237737
TI  - Associations of sirtuins with clinicopathological parameters and prognosis in non
      small cell lung cancer.
AB  - Background: Lung cancer is the leading cause of cancer-related death worldwide
      and it is critical to discover specific biomarkers to provide better
      individualized treatment and subsequently better prognosis. The sirtuins (SIRT1
      7) have been reported to be involved in cancers including non-small cell lung
      cancer (NCSLC), however, the results are not consistent and not all the seven
      sirtuins are explored and compared. Methods: TCGA data was downloaded and used to
      investigate and compare the associations of sirtuins mRNA levels with
      clinicopathological parameters and prognosis in NSCLC. Results: Our results
      suggested SIRT1, SIRT3, SIRT4, and SIRT7 were highly expressed in adeno-carcinoma
      (ADC) patients and female patients while SIRT5 were highly expressed in squamous
      cell carcinoma (SCC) patients and male patients. Associations of high SIRT7 with
      younger onset age, high SIRT1 with distant metastasis and low T stage, and high
      SIRT4 with high T stage and TNM stage were also found. Kaplan-Meier plot curves
      and univariate Cox proportional regression analyses indicated that high SIRT2,
      SIRT4, and SIRT6 expressions were associated with longer overall survival (OS)
      time. Multivariate analyses indicated that SIRT2 and SIRT6 were still associated
      with OS. For recurrence-free survival (RFS), high SIRT1 expression was
      significantly associated with shorter RFS time while high SIRT2-3 and SIRT5-7
      expressions were associated with longer RFS time in univariate analyses. After
      adjusting the confounding factors, significant associations were still found in
      SIRT1-2 and SIRT5-7 but not in SIRT3. We also stratified the patients by
      combining SIRT1 and SIRT2 and revealed that the combination of SIRT1 and SIRT2
      was a better prediction model for RFS in NSCLC. To preliminarily understand the
      potential mechanisms of sirtuins in NSCLC carcinogenesis, the genes co-expressed
      with sirtuins were analyzed and annotated. Conclusion: sirtuins might be the
      potential therapy targets and prognostic biomarkers in NSCLC.

PMID- 30237738
TI  - RBBP6 expressional effects on cell proliferation and apoptosis in breast cancer
      cell lines with distinct p53 statuses.
AB  - Introduction: Breast cancer is the most common malignancy amongst women and has a
      higher incidence rate than lung cancer. Its tumor progression partially results
      from inactivation of p53 which is caused by overexpression of ubiquitous
      regulatory proteins possessing p53-binding domain. RBBP6 is regarded as one of
      the ubiquitous proteins because of its RING finger-like domain which enables it
      to possess E3 ligase activity. Thus, it has become a potential target in cancer
      treatment as it is highly expressed in various malignancies including cancer.
      However, it is not clearly defined whether the effect of RBBP6 on cell growth and
      apoptosis is cell line-dependent, more especially in breast cancer cell lines
      that have distinct p53 expression profiles. This study aims at evaluating the
      effects of RBBP6 on cell growth and apoptosis in breast cancer cell lines with
      different p53 expressions. Methods: Following the analysis at mRNA and protein
      levels in breast cancer tissue, RBBP6 expression was successfully manipulated
      using gene silencing and protein overexpression techniques in MCF-7 and MDA-MB
      231 cell lines. The cells were co-treated with siRBBP6 and anticancer agents
      following apoptosis detection, which was confirmed by caspase 3/7 activity and
      quantification of apoptotic genes. Results: RBBP6 was overexpressed in breast
      cancer tissues that were classified as stages 3 and 4, while in stage 1, its
      expression was much lower. The MCF-7 cell line which expresses wild-type p53 was
      more sensitive to apoptosis induction than MDA-MB-231 which is a mutant p53
      expressing cell line. These data suggest that RBBP6 silencing triggers
      significant levels of intrinsic apoptosis, and its overexpression appears to
      promote cell proliferation in wild-type p53-expressing MCF-7 cell line as opposed
      to MDA-MB-231 cells. Conclusion: The effect of RBBP6 on cell proliferation and
      apoptosis induction in breast cancer seems to be cell line-dependent based on p53
      status.

PMID- 30237739
TI  - The correlation between microRNA-221/222 cluster overexpression and malignancy:
      an updated meta-analysis including 2693 patients.
AB  - Background: Although miR-221/222 cluster plays an important role in many human
      malignancies, the correlation between miR-221/222 cluster overexpression and
      tumor prognosis remains controversial. Therefore, an updated meta-analysis was
      conducted to clarify its prognostic value in malignancy. Methods: We conducted a
      search of literature in English electronic databases of PubMed, Embase, and
      Cochrane Library, and Chinese electronic databases of China Biology Medicine disc
      and China National Knowledge Infrastructure to obtain appropriate studies.
      Besides, we extracted hazard ratios (HRs) and 95% CIs to evaluate the strength of
      the correlations. In addition, the results of different subgroups analyses and
      publication bias test were also shown in this article. Results: 32 publications,
      including 15 tumor types and 2,693 patients were embraced in this meta-analysis.
      The results of univariate (HR =1.69, 95% CI: 1.18-2.44, P<0.01) and multivariate
      (HR =2.10, 95% CI: 1.63-2.69, P<0.01) analyses revealed that miR-221/222 cluster
      high expression in various tumors was significantly associated with adverse
      overall survival (OS). Correspondingly, we also found subgroups analyses
      consisted of country, miR-221/222 cluster component, sample size, and test method
      have similar results. Conclusion: miR-221/222 cluster overexpression was closely
      related to adverse OS in human carcinoma, while overexpression of miRNA-221/222
      cluster could be viewed as a protection factor in prostate cancer. Blood-derived
      miR-221/222 cluster was not proper to assess OS.

PMID- 30237740
TI  - Identification of an eight-gene prognostic signature for lung adenocarcinoma.
AB  - Background: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related
      death worldwide. The main obstacle to early diagnosis or monitoring of patients
      at high risk of poor survival has been the lack of essential predictive
      biomarkers. Methods: RNA-sequencing was performed on LUAD affected tissue and
      paired adjacent to noncancerous tissue samples and Gene Expression Omnibus
      dataset GSE19188 and GSE33532 were used to obtain an intersection of differential
      expressed genes and construct a protein-protein interaction network to get hub
      genes. Then corresponding overall survival information of two cohorts of LUAD
      patients from our hospital and The Cancer Genome Atlas project-LUAD were included
      in the present study. An analysis of the Kyoto Encyclopedia of Genes and Genomes
      database and Gene Ontology were carried out to study the signature mechanism.
      Results: In our study, we identified eight candidate genes (DLGAP5, KIF11,
      RAD51AP1, CCNB1, AURKA, CDC6, OIP5 and NCAPG) closely related to survival in
      LUAD. A linear prognostic model of the eight genes was constructed and weighted
      by the regression coefficient (beta) from the multivariate Cox regression
      analysis of The Cancer Genome Atlas-LUAD cohort to divide patients into low- and
      high-risk groups. The prognostic ability of the signature was validated in LUAD
      patients at our hospital. Patients assigned to the high-risk group exhibited poor
      overall survival compared to patients in the low-risk group. Finally, functional
      enrichment analysis showed that cell division played a vital role in the
      development of LUAD. Conclusion: The study identified an mRNA signature including
      eight genes, which may serve as a potential prognostic marker of LUAD.

PMID- 30237741
TI  - Prognostic value of EGFR and KRAS in resected non-small cell lung cancer: a
      systematic review and meta-analysis.
AB  - Background: The prognostic value of EGFR and KRAS mutations in resected non-small
      cell lung cancer (NSCLC) has been reported. However, conflicting results were
      reported in these studies. The effect of mutations in these two genes in resected
      NSCLC remains controversial. Methods: We searched Internet databases for studies
      reporting disease-free survival (DFS) and overall survival (OS) in resected NSCLC
      patients with EGFR or KRAS mutations. A meta-analysis calculating the pooled
      hazard ratio (HR) for DFS and OS was used to measure the association of EGFR or
      KRAS mutations with the prognosis of patients after surgery. Results: A total of
      9,635 patients from 32 studies were included in this analysis. The combined HR
      for EGFR mutations on DFS was 0.77 (95% CI 0.66-0.90, p=0.001) and on OS was 0.72
      (95% CI 0.66-0.80, p<0.00001). In addition, the combined HR for KRAS mutations on
      DFS was 1.5 (95% CI 1.15-1.96, p=0.002) and on OS was 1.49 (95% CI 1.28-1.73,
      p<0.00001). Sensitivity analysis, subgroup analysis, and bias analysis proved the
      stability of the results. Conclusion: The analysis showed that EGFR mutations
      were significantly associated with DFS and OS. These findings indicated that
      surgically treated NSCLC patients with EGFR mutations were inclined to exhibit a
      prolonged DFS and OS. In addition, the results indicated that KRAS mutations
      predicted worse DFS and OS in patients with resected NSCLC.

PMID- 30237742
TI  - Comparison and validation of the value of preoperative inflammation marker-based
      prognostic scores in resectable pancreatic ductal adenocarcinoma.
AB  - Purpose: We aimed to compare and validate the prognostic value of inflammation
      based prognostic scores for patients with resectable pancreatic ductal
      adenocarcinoma (PDAC) and to establish a novel, effective nomogram incorporating
      inflammation-based prognostic scores to predict disease-free survival (DFS) in
      these patients. Patients and methods: Clinicopathological characteristics and
      follow-up data were retrieved from our prospective database. A total of 420
      patients with PDAC who underwent radical resection were evaluated between January
      2007 and December 2016. Blood samples were obtained within 7 days prior to
      surgical intervention. Time-dependent receiver operating characteristic curves
      were generated to determine optimal cutoff values for independent prognostic
      factors. Nomograms for DFS were established based on multivariate Cox
      proportional hazard models, and the results were internally validated using
      bootstrap resampling. Results: Neutrophil-lymphocyte ratio (NLR) >2.13 and
      platelet-lymphocyte ratio (PLR) >140 were independent prognostic factors for DFS
      and overall survival. Stratified analyses indicated that these associations were
      not present among patients with stage III disease. Independent predictors of DFS,
      including Eastern Cooperative Oncology Group performance status score, tumor
      stage, differentiation, adjuvant treatment, NLR, and PLR, were incorporated into
      two nomograms for prediction of DFS in a cohort of PDAC patients after curative
      surgery. The area under receiver operating characteristic curve of the nomogram
      including NLR and PLR (0.804) was higher than that without NLR and PLR (0.711).
      The bootstrap-corrected AUC for the model including NLR and PLR was 0.803, while
      that for the model without NLR and PLR was 0.711. Conclusion: Our study
      demonstrates that high NLR and high PLR are important clinical predictors of poor
      survival in patients with resectable PDAC. Additionally, a nomogram including NLR
      and PLR can objectively and reliably predict DFS among patients with PDAC
      following curative surgery.

PMID- 30237743
TI  - Checkpoint molecule PD-1-assisted CD8+ T lymphocyte count in tumor
      microenvironment predicts overall survival of patients with metastatic renal cell
      carcinoma treated with tyrosine kinase inhibitors.
AB  - Purpose: The aim of this study was to determine whether CD8+ T lymphocyte and its
      checkpoint-associated module programmed cell death protein 1 (PD-1)/main ligand
      of PD-1 (PD-L1) pathway impact overall survival (OS) in patients with metastatic
      renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs).
      Materials and methods: A total of 231 mRCC patients, from 2007 to 2017, treated
      with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were included
      in the study analyses. CD8, PD-1, and PD-L1 was assessed by immunohistochemistry
      on continuous paraffin-embedded slides. Kaplan-Meier method and COX regression
      model were applied in the survival analyses. Results: Baseline characteristics
      were comparable between the training (n=118) and validation (n=113) sets.
      Patients with high CD8+ T lymphocytes infiltration and low PD-1 expression had
      longer survival in both sets (P=0.0106 and P=0.0047 in training set, P=0.0291 and
      P=0.0011 in validation set, respectively). However, survival stratified by PD-L1
      was only insignificant or marginally significant. Multivariable analyses verified
      that CD8+ T lymphocytes, together with PD-1, but not tumor infiltrating
      mononuclear cells or tumor cells PD-L1, were independent prognostic factors
      (training set [HR 3.202, 95% CI 1.433-7.153, P=0.011] and validation set [HR
      4.012, 95% CI 2.354-6.838, P<0.001]). Subsequent analysis revealed that the PD-1
      high/CD8 low group had shorter survival (16 months) than PD-1 low/CD8 high group
      (51 months, P<0.0001). Combining the International Metastatic Renal Cancer
      Database Consortium system with the PD-1/CD8 model exhibited much better accuracy
      for the prediction of OS. Conclusion: Our findings suggest that abundant CD8+ T
      cells are significantly associated with longer OS in mRCC patients treated with
      TKIs. The most influential checkpoint-associated molecule, PD-1, assisted CD8+ T
      cell-stratified patients and could be used as a better predictive and prognostic
      factor for the mRCC patients.

PMID- 30237744
TI  - Optic nerve sheath meningocele.
AB  - Optic nerve sheath meningocele, also called dural ectasia of the optic nerve, is
      a benign dilation of the optic nerve sheath. We report two interesting cases of
      primary optic nerve sheath meningocele. Etiology, clinical features, and
      management options are discussed.

PMID- 30237745
TI  - In vitro study of RRS(r) Silisorg CE Class III medical device composed of
      silanol: effect on human skin fibroblasts and its clinical use.
AB  - Introduction: Silanol (organic silicon) has been used for decades in the
      treatment of skin photoaging as it stabilizes and maintains skin structures
      through hydrogen bonding electrostatic interaction with extracellular matrix
      (ECM) proteins or glycosaminoglycans. Organic silicon-based products are often
      presented as silanol derivatives which are currently associated to other
      structural molecules such as orthohydroxybenzoate, carboxymethyl theophylline
      alginate, ascorbate, acetyltyrosine, sodium lactate or mannuronate. Consequently,
      organic silicon formulations may differ substantially between the medical devices
      available on the market, which may result in additional effect on the skin.
      Therefore, there is a real need for a better characterization of the products in
      terms of their action on human skin and in vitro skin model. Materials and
      methods: In this in vitro study, the effect of RRS(r) Silisorg was analyzed.
      RRS(r) Silisorg is a dermal implant (CE Class III medical device) containing
      monomethylsilanol mannuronate associated to an antioxidant resveratrol. Skin
      fibroblast viability and capacity to induce the production of key ECM genes were
      evaluated in the presence of different concentrations of RRS(r) Silisorg. The key
      ECM genes selected were collagen type I, elastin and hyaluronan synthase type 2
      (HAS2), which is the cellular enzyme responsible for high-molecular weight
      hyaluronic acid (HA) production. Viability was evaluated through 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and expression was
      quantified by quantitative polymerase chain reaction. Results: RRS(r) Silisorg
      increased fibroblast gene expression of HAS2 in the first 24 hours, 25 times in
      the presence of 1 mg/mL of solution, followed by a collagen type I gene
      expression (4.7 times) and elastin expression (2.5 times) increase after 48
      hours. Conclusion: These results demonstrate that the silanol-based medical
      device RRS(r) Silisorg sustains HA, collagen and elastin production in human skin
      fibroblasts in vitro.

PMID- 30237747
TI  - Amifostine- and chemoradiotherapy-related esophagitis in small cell lung cancer:
      a single institutional series and literature update.
AB  - Objectives: Concurrent chemoradiotherapy is considered a standard option for
      patients with stage 3 small cell lung carcinoma. A 25% risk of acute esophagitis
      is experienced by patients as a result of the volume of esophagus encompassed
      within a conformal radiotherapy technique. We reviewed our institutional
      experience administering the radioprotectant amifostine prior to daily
      radiotherapy to determine its effects on the onset of esophagitis. Materials and
      methods: From 2005 to 2016, 49 patients diagnosed with stage 3 small cell lung
      carcinoma received concurrent chemoradiotherapy. Chemotherapy (CT) consisted of
      cisplatin and etoposide with radiotherapy (RT) encompassing CT-identified gross
      tumor volume. In 32 patients (group 1), amifostine was delivered (500 mg
      subcutaneously divided in two injections) prior to the second daily RT fraction.
      The remaining 17 patients (group 2) did not receive amifostine due to choice or
      drug intolerance. Results: Metrics of esophagitis included weight loss and opiate
      requirement during treatment. About 31% of group 1 required opiates at a median
      RT dose of 3300 cGy, and 41% of group 2 required opiates at a median dose of 2250
      cGy. The dose of radiotherapy delivered to 50% of the esophageal volume for group
      1 was significantly greater than that in group 2 (3000 cGy vs 576 cGy).
      Conclusion: In this modern retrospective series of thoracic chemoradiotherapy in
      the treatment of stage 3 small cell lung cancer, amifostine that was delivered
      subcutaneously postponed the onset of esophagitis.

PMID- 30237746
TI  - Progressive familial intrahepatic cholestasis: diagnosis, management, and
      treatment.
AB  - Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal
      recessive cholestatic liver diseases which are subgrouped according to the
      genetic defect, clinical presentation, laboratory findings and liver histology.
      Progressive liver fibrosis, cirrhosis, and end stage liver disease (ESLD) may
      eventually develop. PFIC was first described in Amish descendants of Jacob Byler,
      therefore it was originally called Byler disease. But it can be seen anywhere on
      the globe. This review summarizes the main features of the subtypes of the
      disease and discusses the current available diagnosis, conservative and surgical
      therapeutic options.

PMID- 30237749
TI  - Green method for efficient PdNPs deposition on carbon carrier in the microreactor
      system.
AB  - The synthesis of palladium nanoparticles and conditions of their deposition on
      active carbon fibers in the microreactor was described. All processes related
      with metal ion reduction, nucleation, and autocatalytic growth of particles as
      well as their deposition were carried out in the microreactor in only one cycle.
      Synthesis of palladium nanoparticles was carried out under different conditions,
      i.e., changing the initial concentration of metal ions and the reductant, at 40 
      degrees C. Depending on the conditions imposed, the nanoparticles of different
      size (hydrodynamic radius change from 12 to 37 nm) and shape (spherical, cube,
      pyramid) were obtained. It was also shown that flow conditions allow for much
      more efficient Pd deposition on active carbon fibers than the process carried out
      in the batch. It was observed that for concentrations of Pd(II) ions higher than
      0.2 mM, the degree of fiber surface coverage increased significantly in
      comparison with the batch process.

PMID- 30237748
TI  - Genetic mapping of ovary colour and quantitative trait loci for carotenoid
      content in the fruit of Cucurbita maxima Duchesne.
AB  - The high content of carotenoids, sugars, dry matter, vitamins and minerals makes
      the fruit of winter squash (Cucurbita maxima Duchesne) a valuable fresh-market
      vegetable and an interesting material for the food industry. Due to their
      nutritional value, long shelf-life and health protective properties, winter
      squash fruits have gained increased interest from researchers in recent years.
      Despite these advantages, the genetic and genomic resources available for C.
      maxima are still limited. The aim of this study was to use the genetic mapping
      approach to map the ovary colour locus and to identify the quantitative trait
      loci (QTLs) for high carotenoid content and flesh colour. An F6 recombinant
      inbred line (RIL) mapping population was developed and used for evaluations of
      ovary colour, carotenoid content and fruit flesh colour. SSR markers and DArTseq
      genotyping-by-sequencing were used to construct an advanced genetic map that
      consisted of 1824 molecular markers distributed across linkage groups
      corresponding to 20 chromosomes of C. maxima. Total map length was 2208 cM and
      the average distance between markers was 1.21 cM. The locus affecting ovary
      colour was mapped at the end of chromosome 14. The identified QTLs for carotenoid
      content in the fruit and fruit flesh colour shared locations on chromosomes 2, 4
      and 14. QTLs on chromosomes 2 and 4 were the most meaningful. A correlation was
      clearly confirmed between fruit flesh colour as described by the chroma value and
      carotenoid content in the fruit. A high-density genetic map of C. maxima with
      mapped loci for important fruit quality traits is a valuable resource for winter
      squash improvement programmes.

PMID- 30237750
TI  - Hamiltonian formulation of general relativity and post-Newtonian dynamics of
      compact binaries.
AB  - Hamiltonian formalisms provide powerful tools for the computation of approximate
      analytic solutions of the Einstein field equations. The post-Newtonian
      computations of the explicit analytic dynamics and motion of compact binaries are
      discussed within the most often applied Arnowitt-Deser-Misner formalism. The
      obtention of autonomous Hamiltonians is achieved by the transition to Routhians.
      Order reduction of higher derivative Hamiltonians results in standard
      Hamiltonians. Tetrad representation of general relativity is introduced for the
      tackling of compact binaries with spinning components. Configurations are treated
      where the absolute values of the spin vectors can be considered constant. Compact
      objects are modeled by use of Dirac delta functions and their derivatives.
      Consistency is achieved through transition to d-dimensional space and application
      of dimensional regularization. At the fourth post-Newtonian level, tail
      contributions to the binding energy show up. The conservative spin-dependent
      dynamics finds explicit presentation in Hamiltonian form through next-to-next-to
      leading-order spin-orbit and spin1-spin2 couplings and to leading-order in the
      cubic and quartic in spin interactions. The radiation reaction dynamics is
      presented explicitly through the third-and-half post-Newtonian order for spinless
      objects, and, for spinning bodies, to leading-order in the spin-orbit and spin1
      spin2 couplings. The most important historical issues get pointed out.

PMID- 30237751
TI  - Design and evaluation of the StartingTogether App for home visits in preventive
      child health care.
AB  - Background: The StartingTogether program (in Dutch SamenStarten) is a family
      centred method for early identification of social-emotional and behavioural
      problems in young children. Nurses in preventive child health care find it
      challenging to: determine family issues and need for care; provide education;
      refer to social services; increase parent empowerment. To mitigate these
      challenges, we developed and evaluated the StartingTogether App, offering nurses
      and parents conversational support, tailored education and information on social
      services. Methods: A mixed method design, consisting of a qualitative evaluation
      of the StartingTogether App, with group discussions with nurses (N = 14) and a
      pilot test (N = 5), and a randomized controlled trial, evaluating the
      effectiveness of the app. Nurses (N = 33) made home visits to parents (N = 194),
      in teams with or without the app. Nurses were surveyed on the challenges
      experienced during visits. Parents (N = 166) were surveyed on their satisfaction
      with health care and app. Nurses were interviewed on the benefits and barriers to
      use the app. Results: Parents with the StartingTogether App were more satisfied
      with the visits than parents without (p = .002). Parents with a high educational
      level were more satisfied with the visits than the parents with a low educational
      level. With the app, their satisfaction level was similar (p < .001). Nurses
      using the app felt more equipped to communicate with parents (p = .012) and
      experienced that parents were more knowledgeable and skilled (p = .001). Parents
      felt that with the app the nurse was more polite (p = .02), listened more
      carefully (p = .03), and had more time (p = .02). Nurses with the app gave
      parents more opportunity to ask questions (p = .001) and gave clearer answers (p
      < .001). The qualitative evaluation indicated that some nurses needed extra time
      to develop the habit of using the app. Conclusions: The StartingTogether App
      contributes to parents' satisfaction with home visits. An interaction effect
      between parents' educational level and rating of home visits indicated that the
      app has an additional value for parents with a lower educational level. Applying
      mobile applications, such as the StartingTogether App, potentially has a positive
      effect on communication between nurses and parents about the family situation in
      relation to parent empowerment and the child's development. Trial registration:
      The study is registered with ISRCTN under the number ISRCTN12491485, on August
      23, 2018. Retrospectively registered.

PMID- 30237752
TI  - Identification of critical genes to predict recurrence and death in colon cancer:
      integrating gene expression and bioinformatics analysis.
AB  - Background: The purpose of this study was to screen the critical genes for future
      diagnosis and treatment of colon cancer by bioinformatics method. Methods: In
      this study, we used bioinformatics approaches to identify gene alteration that
      contribute to colon cancer progression via analysis of TCGA RNA sequencing data
      and other publicly GEO microarray data. The Random forest survival model was used
      to screen gene sets related to the prognosis in DEGs. Gene ontology and KEGG
      pathway enrichment analysis were performed to determine the potential function of
      DEGs. Results: We identified versican (VCAN), a member of the aggrecan/versican
      proteoglycan family, as a key regulator in human colon cancer development and
      progression involved in cell adhesion, proliferation, migration and angiogenesis
      and plays a central role in tissue morphogenesis and maintenance. Interestingly,
      we found that VCAN is highly over-expressed in colon cancer and increased
      expression of VCAN was associated with the progression of colon cancer. High VCAN
      levels also predict shorter overall survival of colon cancer patients.
      Furthermore, in vitro assays of silencing VCAN inhibit HCT116 cell proliferation
      and invasion. Conclusions: These data demonstrated VCAN were associated with
      tumorigenesis and may be as biomarker for identification of the pathological
      grade of colon cancer.

PMID- 30237753
TI  - Poor outcomes associated with antithrombotic undertreatment in patients with
      atrial fibrillation attending Gondar University Hospital: a retrospective cohort
      study.
AB  - Background: Atrial fibrillation (AF) is a major risk factor for stroke as it
      increases the incidence of stroke nearly fivefold. Antithrombotic treatment is
      recommended for the prevention of stroke in AF patients. However, majorly due to
      fear of risk of bleeding, adherence to recommendations is not observed. The aim
      of this study was to investigate the impact of antithrombotic undertreatment, on
      ischemic stroke and/or all-cause mortality in patients with AF. Methods: A
      retrospective cohort study was conducted from January 7, 2017 to April 30 2017
      using medical records of patients with AF attending Gondar University Hospital
      (GUH) between November 2012 and September 2016. Patients receiving appropriate
      antithrombotic management and those on undertreatment, were followed for
      development of ischemic stroke and/or all-cause mortality. Kaplan-Meier and a log
      rank test was used to plot the survival analysis curve. Cox regression was used
      to determine the predictors of guideline-adherent antithrombotic therapy.
      Results: The final analysis included 159 AF patients with a median age of 60
      years. Of these, nearly two third (64.78%) of patients were receiving
      undertreatment for antithrombotic medications. Upon multivariate analysis,
      history of ischemic stroke/transient ischemic attack (TIA) was associated with
      lower incidence of antithrombotic undertreatment. A significant increase (HR:
      8.194, 95% CI: 2.911-23.066)] in the incidence of ischemic stroke and/or all
      cause mortality was observed in patients with undertreatment. Up-on multivariate
      analysis, only increased age was associated with a statistically significant
      increase incidence of ischemic stroke and/or all-cause mortality, while only
      history of ischemic stroke/TIA was associated with a decrease in the risk of
      ischemic stroke and/or all-cause mortality. Conclusion: Adherence to
      antithrombotic guideline recommendations was found to be crucial in reducing the
      incidence of ischemic stroke and/or all-cause mortality in patients with AF
      without increasing the risk of bleeding. However, undertreatment to
      antithrombotic medications was found to be high (64.78%) and was associated with
      poorer outcomes in terms of ischemic stroke and/or all-cause mortality. Impact on
      practice: This research highlighted the magnitude of antithrombotic
      undertreatment and its impact on ischemic stroke and/or all-cause mortality in
      patients with AF. This article has to alert prescribers to routinely evaluate AF
      patients' risk for ischemic stroke and provide appropriate interventions based on
      guideline recommendations.

PMID- 30237754
TI  - Evaluating the health system financing of the Eastern Mediterranean Region (EMR)
      countries using Grey Relation Analysis and Shannon Entropy.
AB  - Background: Sufficient and sustainable financing of the health system is
      essential for improving the health of the community. The health systems financing
      of the EMR countries is facing the challenge. Assessment and ranking of
      healthcare financing can help identify and resolve some challenges of health
      systems. So, the aim of this study is to evaluate and rank the condition of the
      health sector financing in the EMR countries. Methods: This study was a cross
      sectional study. The data was of secondary type, extracted from the official WHO
      and World Bank data. The six healthcare financing indicators in a 10-year
      interval (2005-2014) in 19 EMR countries analyzed using Grey Relation Analysis
      and Shannon Entropy. Results: On average, the countries in the EMR region spent
      4.87% of their GDP on the health sector. Jordan and Qatar allocated the highest
      (8.313) and the lowest (2.293) percentages of their GDP to the health sector,
      respectively. The results showed That Qatar was in a better condition than other
      EMR countries during 2005-2014 in terms of the health system financing and earned
      the first rank. After that, the UAE and Kuwait were ranked second and third.
      Conclusions: There is a lot of inequality among the EMR countries in terms of
      health financing. However, our findings confirmed that only increasing the total
      health expenditure in a country would not improve its financing status compared
      to other countries, but it also depends on financing methods.

PMID- 30237755
TI  - Effect of Two Oat-based Cereals on Subjective Ratings of Appetite.
AB  - Viscosity generated by oat beta-glucan induces gastrointestinal mechanisms that
      influence appetite. Two oat-based ready-to-eat cereals (RTEC) with similar
      amounts of beta-glucan but differing in their protein and sugar content were
      compared for their effects on appetite. Forty-seven healthy individuals, >=18
      years old, enrolled in a crossover trial consumed RTEC1 or RTEC2 in random order
      at least a week apart. Breakfasts contained 250kcals cereal and 105kcals fat-free
      milk. Subjective ratings of appetite were completed at baseline, and at 30, 60,
      120, 180 and 240 minutes after consumption of the breakfast meals. Responses were
      analyzed as area under the curve (AUC) and per time-point. Significance was set
      at alpha=0.05. Fullness (p=0.01) and stomach fullness (p=0.02) were greater with
      RTEC 1 compared to RTEC 2 at 240 minutes. Stomach fullness (p=0.01) was greater
      at 30 minutes, and desire to eat (p=0.04) was reduced at 120 minutes with RTEC2
      compared to RTEC1. There was no difference in the AUC for hunger, fullness,
      stomach fullness, desire to eat, or prospective intake. Ready-to-eat cereals
      containing similar amounts of oat beta-glucan differed in the timing of
      significant differences in fullness or desire to eat, but appetite ratings over a
      four hour period did not differ.

PMID- 30237757
TI  - Adherence to the Healthy Nordic Food Index in the Norwegian Women and Cancer
      (NOWAC) cohort.
AB  - Background: High adherence to the Healthy Nordic Food Index has been associated
      with better health outcomes, but the results have not been consistent. The
      association between high adherence and higher intake of energy and healthy and
      less healthy foods has been persistent across countries, highlighting the need to
      examine potential confounding by energy intake. Objective: This study aimed to
      examine energy-adjusted dietary factors and lifestyle factors related to the
      index in a Norwegian context. Design: The study was cross-sectional within the
      Norwegian Women and Cancer cohort and included 81,516 women aged 41-76.
      Information about habitual food intake was based on a food frequency
      questionnaire (FFQ). The index incorporated six food groups (fish, root
      vegetables, cabbages, apples/pears, whole grain bread, and breakfast cereals).
      Ordered trend and regression analyses were performed to assess the association
      between the index and lifestyle and dietary factors with energy-adjusted models.
      Results: Nearly one out of four women (22.8%) had low adherence, 49.0% had medium
      adherence, and 28.2% had high adherence to the index. Intake of energy and of
      both healthy and less healthy foods increased with increased adherence. Energy
      adjustment removed the associations between less healthy foods and high adherence
      and demonstrated a better dietary composition in high adherers. The healthy
      Nordic foods contributed more to the total food intake in high versus low
      adherers, and high adherence was associated with a healthier lifestyle.
      Conclusion: High adherence was associated with a healthier lifestyle, both
      concerning diet and other factors. Energy adjustment of potential confounding
      foods removed associations between high adherence and less healthy foods. The
      Nordic foods accounted for a larger fraction of the diet among high adherers, at
      the expense of other healthy foods. Careful adjustment for confounders is
      warranted when assessing associations between the index and health outcomes.

PMID- 30237756
TI  - The Molecular Basis of Metastatic Colorectal Cancer.
AB  - Purpose of review: Metastatic colorectal cancer (CRC) is a vexing clinical
      problem. In contrast to early stage disease, once CRC metastasizes to other
      organs, long-term survival is compromised. We seek to review the molecular
      pathogenesis, animal models, and functional genomics for an enhanced
      understanding of how CRC metastasizes and how this can be exploited
      therapeutically. Recent findings: Mouse models may recapitulate certain aspects
      of metastatic human CRC and allow for studies to identify regulators of
      metastasis. Modulation of transcription factors, onco-proteins, or tumor
      suppressors have been identified to activate known metastatic pathways. CD44
      variants, microRNAs and RNA binding proteins are emerging as metastatic
      modulators. Summary: CRC metastasis is a multi-faceted and heterogeneous disease.
      Despite common pathways contributing to metastatic development, there are
      numerous variables that modulate metastatic signals in subsets of patients. It is
      paramount that studies continue to investigate metastatic drivers, enhancers and
      inhibitors in CRC to develop therapeutic targets and improve disease outcomes.

PMID- 30237758
TI  - Resting-State fMRI Dynamics and Null Models: Perspectives, Sampling Variability,
      and Simulations.
AB  - Studies of resting state functional MRI (rs-fRMI) are increasingly focused on
      "dynamics", or on those properties of brain activation that manifest and vary on
      timescales shorter than the scan's full duration. This shift in focus has led to
      a flurry of interest in developing hypothesis testing frameworks and null models
      applicable to the dynamical setting. Thus far however, these efforts have been
      weakened by a number of crucial shortcomings that are outlined and discussed in
      this article. We focus here on aspects of recently proposed null models that, we
      argue, are poorly formulated relative to the hypotheses they are designed to
      test, i.e., their potential role in separating functionally relevant BOLD signal
      dynamics from noise or intermittent background and maintenance type processes is
      limited by factors that are fundamental rather than merely quantitative or
      parametric. In this short position paper, we emphasize that (1) serious care must
      be exercised in building null models for rs-fMRI dynamics from distributionally
      stationary univariate or multivariate timeseries, i.e., timeseries whose values
      are each independently drawn from one pre-specified probability distribution; and
      (2) measures such as kurtosis that quantify over-concentration of observed values
      in the far tails of some reference distribution may not be particularly suitable
      for capturing signal features most plausibly contributing to functionally
      relevant brain dynamics. Other metrics targeted, for example, at capturing the
      type of epochal signal variation that is often viewed as a signature of brain
      responsiveness to stimuli or experimental tasks, could play a more scientifically
      clarifying role. As we learn more about the phenomenon of functionally relevant
      brain dynamics and its imaging correlates, scientifically meaningful null
      hypotheses and well-tuned null models will naturally emerge. We also revisit the
      important concept of distributional stationarity, discuss how it manifests within
      realizations vs. across multiple realizations, and provide guidance on the
      benefits and limitations of employing this type of stationarity in modeling the
      absence of functionally relevant temporal dynamics in resting state fMRI. We hope
      that the discussions herein are useful, and promote thoughtful consideration of
      these important issues.

PMID- 30237759
TI  - The Argus-II Retinal Prosthesis Implantation; From the Global to Local Successful
      Experience.
AB  - Over the past few years, visual prostheses (namely, Argus II retinal implant) and
      gene therapy have obtained FDA approval in treating blindness resulting from
      retinitis pigmentosa. Compared to gene therapy; Argus II is less costly with a
      demonstrated favorable outcome, though the vision is yet artificial. To obtain
      better results, expectation counseling and preoperative retinal assessment are
      critical. The global experience with Argus II has enrolled no more than 300 cases
      so far. The first Argus II retinal prosthesis in Iran was successfully implanted
      in Shiraz (October 2017). To date, Argus II artificial retina is implanted in
      four patients in Iran. Beside successful surgery and post-operative care,
      rehabilitation efforts with validated outcome measures including visual
      rehabilitation together with neurovisual, visuo-constructive and cognitive
      rehabilitation/empowerment approaches are expected to boost the functional
      outcome. A multidisciplinary approach within a cross-functional team would
      optimize strategies toward better patient outcomes. As such, establishing a
      collaborative network will foster organized research efforts to better define
      outcome assessment and rehabilitation strategies. This technology report paper
      has been an attempt to provide an overview of Argus-II retinal implant global
      experience as well as the clinical outcome of the so far cases in Iran. Insights
      from this report were communicated during the first "Brain Engineering and
      Computational Neuroscience Conference," 31 January-2 February 2018 in Tehran.

PMID- 30237760
TI  - Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From
      Cartilaginous Fish: Evolutionary Perspectives.
AB  - The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in
      the control of reproductive functions. Vertebrates possess multiple GnRH forms
      that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In
      order to gain more insights into the GnRH gene family in vertebrates, we sought
      to identify which paralogs of this family are present in cartilaginous fish. For
      this purpose, we searched the genomes and/or transcriptomes of three
      representative species of this group, the small-spotted catshark, Scyliorhinus
      canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus
      milii. In each species, we report the identification of three GnRH genes. In
      catshark and whale shark, phylogenetic and synteny analysis showed that these
      three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was
      found to encode a novel form of GnRH whose primary structure was determined as
      follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and
      GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the
      chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2,
      and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This
      structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological
      activity. This HLH structure could not be observed for elephant shark GAP1a and
      GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was
      observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1,
      GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1
      mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed
      to be most abundant in the mesencephalon and telencephalon, respectively. Taken
      together, our results show that the GnRH gene repertoire of the vertebrate
      ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3
      gene was probably lost in holocephali. They also suggest that the three GnRH
      neuronal systems previously described in the brain of bony vertebrates are also
      present in cartilaginous fish.

PMID- 30237761
TI  - Brain Endothelial Erythrophagocytosis and Hemoglobin Transmigration Across Brain
      Endothelium: Implications for Pathogenesis of Cerebral Microbleeds.
AB  - Peripheral endothelial cells are capable of erythrophagocytosis, but data on
      brain endothelial erythrophagocytosis are limited. We studied the relationship
      between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the
      pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate
      the erythrophagocytic capability of the brain endothelium, we studied the
      interactions between brain endothelial cells and red blood cells exposed to
      oxidative stress in vitro, and developed a new in vitro cerebral microbleeds
      model to study the subsequent passage of hemoglobin across the brain endothelial
      monolayer. Using multiple approaches, our results show marked brain endothelial
      erythrophagocytosis of red blood cells exposed to oxidative stress compared with
      control red blood cells in vitro. This brain endothelial erythrophagocytosis was
      accompanied by passage of hemoglobin across the brain endothelial monolayer with
      unaltered monolayer integrity. In vivo and confocal fluorescence microscopy
      studies confirmed the extravasation of RBC exposed to oxidative stress across
      brain endothelium. These findings, demonstrating erythrophagocytosis mediated by
      the brain endothelial monolayer and the subsequent passage of iron-rich
      hemoglobin in vitro and RBC in vivo, may have implications for elucidating
      mechanisms involved in the development of cerebral microbleeds that are not
      dependent on disruption of the microvasculature.

PMID- 30237763
TI  - Developmental and Repairing Production of Myelin: The Role of Hedgehog Signaling.
AB  - Since the discovery of its role as a morphogen directing ventral patterning of
      the spinal cord, the secreted protein Sonic Hedgehog (Shh) has been implicated in
      a wide array of events contributing to the development, maintenance and repair of
      the central nervous system (CNS). One of these events is the generation of
      oligodendrocytes, the glial cells of the CNS responsible for axon myelination. In
      embryo, the first oligodendroglial cells arise from the ventral ventricular zone
      in the developing brain and spinal cord where Shh induces the basic helix-loop
      helix transcription factors Olig1 and Olig2 both necessary and sufficient for
      oligodendrocyte production. Later on, Shh signaling participates in the
      production of oligodendroglial cells in the dorsal ventricular-subventricular
      zone in the postnatal forebrain. Finally, the modulation of Hedgehog signaling
      activity promotes the repair of demyelinated lesions. This mini-review article
      focuses on the Shh-dependent molecular mechanisms involved in the spatial and
      temporal control of oligodendrocyte lineage appearance. The apparent intricacy of
      the roles of two essential components of Shh signaling, Smoothened and Gli1, in
      the postnatal production of myelin and its regeneration following a demyelinating
      event is also highlighted. A deeper understanding of the implication of each of
      the components that regulate oligodendrogenesis and myelination should
      beneficially influence the therapeutic strategies in the field of myelin
      diseases.

PMID- 30237762
TI  - Cortical Reshaping and Functional Recovery Induced by Silk Fibroin Hydrogels
      Encapsulated Stem Cells Implanted in Stroke Animals.
AB  - The restitution of damaged circuitry and functional remodeling of peri-injured
      areas constitute two main mechanisms for sustaining recovery of the brain after
      stroke. In this study, a silk fibroin-based biomaterial efficiently supports the
      survival of intracerebrally implanted mesenchymal stem cells (mSCs) and increases
      functional outcomes over time in a model of cortical stroke that affects the
      forepaw sensory and motor representations. We show that the functional mechanisms
      underlying recovery are related to a substantial preservation of cortical tissue
      in the first days after mSCs-polymer implantation, followed by delayed cortical
      plasticity that involved a progressive functional disconnection between the
      forepaw sensory (FLs1) and caudal motor (cFLm1) representations and an emergent
      sensory activity in peri-lesional areas belonging to cFLm1. Our results provide
      evidence that mSCs integrated into silk fibroin hydrogels attenuate the cerebral
      damage after brain infarction inducing a delayed cortical plasticity in the peri
      lesional tissue, this later a functional change described during spontaneous or
      training rehabilitation-induced recovery. This study shows that brain remapping
      and sustained recovery were experimentally favored using a stem cell-biomaterial
      based approach.

PMID- 30237764
TI  - Distinct Patterns of Interhemispheric Connectivity in Patients With Early- and
      Late-Onset Alzheimer's Disease.
AB  - Background: Early-onset Alzheimer's disease (EOAD) presents a different clinical
      profile than late-onset Alzheimer's disease (LOAD). Neuroimaging studies have
      demonstrated that patients with EOAD present more atrophy and functional
      disconnection than LOAD patients. However, it remains unknown whether the
      interhemispheric functional disconnection or its underlying structural impairment
      contributes to the different clinical profiles of EOAD and LOAD. Methods:
      According to the arbitrary cut-off age of 65, we included 22 EOAD patients, 27
      LOAD patients and 38 healthy controls (further divided into 21 relatively young
      and 17 old controls). Participants underwent resting-state functional MRI,
      diffusion tensor imaging (DTI) and comprehensive neuropsychological assessments.
      We used voxel-mirrored homotopic connectivity (VMHC) to examine interhemispheric
      functional connectivity. Then, we calculated the diffusion index based on tract
      based spatial statistics (TBSS). Two-sample t-tests were used to assess the
      interhemispheric connectivity differences between each patient group and its
      corresponding control group. Results: We found that the EOAD patients had lower
      VMHC in the hippocampus, parahippocampal gyrus (PHG), superior temporal gyrus
      (STG) and inferior parietal cortex (IPC) than did controls. Consistently, the
      EOAD patients exhibited white matter (WM) tract impairment in the posterior
      regions. On the other hand, the LOAD patients displayed increased VMHC and
      impaired WM tracts in the frontal region. Correlation analyses showed that VMHC
      in the IPC was related to executive function in the EOAD patients (r = -0.67, P <
      0.05). Conclusion: In contrast to the LOAD patients, patients with EOAD exhibited
      more widely disrupted interhemispheric functional and structural connectivity,
      which overlapped well across brain regions. In addition, for the EOAD patients,
      decreased interhemispheric connectivity related to executive deficits. Our study
      suggested that different interhemispheric connectivity damage patterns may
      contribute to the distinct clinical profiles in EOAD and LOAD.

PMID- 30237766
TI  - Characterizing Electrogram Signal Fidelity and the Effects of Signal
      Contamination on Mapping Human Persistent Atrial Fibrillation.
AB  - Objective: Determining accurate intracardiac maps of atrial fibrillation (AF) in
      humans can be difficult, owing primarily to various sources of contamination in
      electrogram signals. The goal of this study is to develop a measure for signal
      fidelity and to develop methods to quantify robustness of observed rotational
      activity in phase maps subject to signal contamination. Methods: We identified
      rotational activity in phase maps of human persistent AF using the Hilbert
      transform of sinusoidally recomposed signals, where localized ablation at
      rotational sites terminated fibrillation. A novel measure of signal fidelity was
      developed to quantify signal quality. Contamination is then introduced to the
      underlying electrograms by removing signals at random, adding noise to
      computations of cycle length, and adding realistic far-field signals. Mean tip
      number N and tip density delta, defined as the proportion of time a region
      contains a tip, at the termination site are computed to compare the effects of
      contamination. Results: Domains of low signal fidelity correspond to the location
      of rotational cores. Removing signals and altering cycle length accounted for
      minor changes in tip density, while targeted removal of low fidelity electrograms
      can result in a significant increase in tip density and stability. Far-field
      contamination was found to obscure rotation at the termination site. Conclusion:
      Rotational activity in clinical AF can produce domains of low fidelity
      electrogram recordings at rotational cores. Observed rotational patterns in phase
      maps appear most sensitive to far-field activation. These results may inform
      novel methods to map AF in humans which can be tested directly in patients at
      electrophysiological study and ablation.

PMID- 30237765
TI  - Rapamycin Treatment Ameliorates Age-Related Accumulation of Toxic Metabolic
      Intermediates in Brains of the Ts65Dn Mouse Model of Down Syndrome and Aging.
AB  - Down syndrome (DS), caused by trisomy of chromosome 21, is the most common
      genetic cause of intellectual disability. Individuals with DS exhibit changes in
      neurochemistry and neuroanatomy that worsen with age, neurological delay in
      learning and memory, and predisposition to Alzheimer's disease. The Ts65Dn mouse
      is the best characterized model of DS and has many features reminiscent of DS,
      including developmental anomalies and age-related neurodegeneration. The mouse
      carries a partial triplication of mouse chromosome 16 containing roughly 100
      genes syntenic to human chromosome 21 genes. We hypothesized that there would be
      differences in brain metabolites with trisomy and age, and that long-term
      treatment with rapamycin, mechanistic target of rapamycin (mTOR) inhibitor and
      immunosuppressant, would correct these differences. Using HPLC coupled with
      electrochemical detection, we identified differences in levels of metabolites
      involved in dopaminergic, serotonergic, and kynurenine pathways in trisomic mice
      that are exacerbated with age. These include homovanillic acid, norepinephrine,
      and kynurenine. In addition, we demonstrate that prolonged treatment with
      rapamycin reduces accumulation of toxic metabolites (such as 6-hydroxymelatonin
      and 3-hydroxykynurenine) in aged mice.

PMID- 30237767
TI  - Applications of Variability Analysis Techniques for Continuous Glucose Monitoring
      Derived Time Series in Diabetic Patients.
AB  - Methods from non-linear dynamics have enhanced understanding of functional
      dysregulation in various diseases but received less attention in diabetes. This
      retrospective cross-sectional study evaluates and compares relationships between
      indices of non-linear dynamics and traditional glycemic variability, and their
      potential application in diabetes control. Continuous glucose monitoring provided
      data for 177 subjects with type 1 (n = 22), type 2 diabetes (n = 143), and 12 non
      diabetic subjects. Each time series comprised 576 glucose values. We calculated
      Poincare plot measures (SD1, SD2), shape (SFE) and area of the fitting ellipse
      (AFE), multiscale entropy (MSE) index, and detrended fluctuation exponents
      (alpha1, alpha2). The glycemic variability metrics were the coefficient of
      variation (%CV) and standard deviation. Time of glucose readings in the target
      range (TIR) defined the quality of glycemic control. The Poincare plot indices
      and alpha exponents were higher (p < 0.05) in type 1 than in the type 2 diabetes;
      SD1 (mmol/l): 1.64 +/- 0.39 vs. 0.94 +/- 0.35, SD2 (mmol/l): 4.06 +/- 0.99 vs.
      2.12 +/- 1.04, AFE (mmol2/l2): 21.71 +/- 9.82 vs. 7.25 +/- 5.92, and alpha1: 1.94
      +/- 0.12 vs. 1.75 +/- 0.12, alpha2: 1.38 +/- 0.11 vs. 1.30 +/- 0.15. The MSE
      index decreased consistently from the non-diabetic to the type 1 diabetic group
      (5.31 +/- 1.10 vs. 3.29 +/- 0.83, p < 0.001); higher indices correlated with
      lower %CV values (r = -0.313, p < 0.001). In a subgroup of type 1 diabetes
      patients, insulin pump therapy significantly decreased SD1 (-0.85 mmol/l), SD2 (
      1.90 mmol/l), and AFE (-16.59 mmol2/l2), concomitantly with %CV (-15.60). The MSE
      index declined from 3.09 +/- 0.94 to 1.93 +/- 0.40 (p = 0.001), whereas the
      exponents alpha1 and alpha2 did not. On multivariate regression analyses, SD1,
      SD2, SFE, and AFE emerged as dominant predictors of TIR (beta = -0.78, -1.00, 
      0.29, and -0.58) but %CV as a minor one, though alpha1 and MSE failed. In the
      regression models, including SFE, AFE, and alpha2 (beta = -0.32), %CV was not a
      significant predictor. Poincare plot descriptors provide additional information
      to conventional variability metrics and may complement assessment of glycemia,
      but complexity measures produce mixed results.

PMID- 30237768
TI  - Relationship Between Toe Clearance Strategy and Regional Regulation of Rectus
      Femoris Muscle During Swing Phase in Prolonged Walking in Young and Older Adults.
AB  - The toe clearance strategy during leg swinging while walking is closely
      associated with the risk of tripping and/or falling and is influenced by aging
      and a fall history. However, it remains unclear how the toe clearance strategy is
      regulated by the neuromuscular system. The present study investigated the effect
      of aging and fall/tripping history in the older adults on the toe clearance
      strategy and neuromuscular regulation of the rectus femoris (RF) muscle, which
      plays an important role in leg swinging, during prolonged walking. Thirteen older
      adults (age: 71.3 +/- 5.7 years) and nine young adults (age: 20.9 +/- 0.8 years)
      men volunteered for the present study. The older adults were divided into those
      with (n = 6) and without (n = 7) a fall/tripping history. Subjects walked on a
      treadmill at their preferred gait speed for 20 min, and lower extremity
      kinematics and multi-channel surface electromyography along the RF muscle were
      recorded. Variability of the minimum toe clearance (MTC) and central locus
      activation (CLA) of the RF muscle in older adults was significantly greater than
      in the young adults (p < 0.05). MTC significantly decreased with time in the
      older adults (p < 0.05), but not in the young adults (p > 0.05). There were no
      significant correlations between any parameters of MTC and CLA in the older
      adults or young adults (p > 0.05). MTC and variability of CLA significantly
      decreased with time in the older adults without a fall/tripping history (p <
      0.05), but not in the older adults with such a history (p > 0.05). These results
      suggest that aging and a fall/tripping history in the older adults alter the toe
      clearance strategy and regional neural regulation of the RF muscle during
      prolonged walking.

PMID- 30237770
TI  - Editorial: Neural Mechanisms Underlying Internet Gaming Disorder.

PMID- 30237769
TI  - EEG Microstates Indicate Heightened Somatic Awareness in Insomnia: Toward
      Objective Assessment of Subjective Mental Content.
AB  - People with Insomnia Disorder (ID) not only experience abundant nocturnal
      mentation, but also report altered spontaneous mental content during daytime
      wakefulness, such as an increase in bodily experiences (heightened somatic
      awareness). Previous studies have shown that resting-state EEG can be temporally
      partitioned into quasi-stable microstates, and that these microstates form a
      small number of canonical classes that are consistent across people. Furthermore,
      the microstate classes have been associated with individual differences in
      resting mental content including somatic awareness. To address the hypothesis
      that altered resting mental content in ID would be reflected in an altered
      representation of the corresponding EEG microstates, we analyzed resting-state
      high-density EEG of 32 people with ID and 32 age- and sex-matched controls
      assessed during 5-min eyes-closed wakefulness. Using data-driven topographical k
      means clustering, we found that 5 microstate classes optimally explained the EEG
      scalp voltage map sequences across participants. For each microstate class, 3
      dynamic features were obtained: mean duration, frequency of occurrence, and
      proportional coverage time. People with ID had a shorter mean duration of class C
      microstates, and more frequent occurrence of class D microstates. The finding is
      consistent with previously established associations of these microstate
      properties with somatic awareness, and increased somatic awareness in ID. EEG
      microstate assessment could provide objective markers of subjective experience
      dimensions in studies on consciousness during the transition between wake and
      sleep, when self-report is not possible because it would interfere with the very
      process under study. Addressing somatic awareness may benefit psychotherapeutic
      treatment of insomnia.

PMID- 30237772
TI  - Understanding Another Person's Emotions-An Interdisciplinary Research Approach.
AB  - An interdisciplinary research perspective is developed concerning the question of
      how we understand others' emotions and how reliable our judgment about others'
      emotion can be. After an outline of the theoretical background of emotions, we
      briefly discuss the importance of prior experiences and context information for
      the recognition of emotions. To clarify this role, we describe a study design,
      utilizing emotional expressions and context information while controlling for
      prior experiences and the actual emotional situation to systematically approach
      these questions.

PMID- 30237771
TI  - Caffeine Modulates Food Intake Depending on the Context That Gives Access to
      Food: Comparison With Dopamine Depletion.
AB  - Caffeine is a methylxanthine consumed in different contexts to potentiate
      alertness and reduce fatigue. However, caffeine can induce anxiety at high doses.
      Caffeine is also a minor psychostimulant that seems to act as an appetite
      suppressant, but there are also reports indicating that it could stimulate
      appetite. Dopamine also is involved in food motivation and in behavioral
      activation. In the present series of experiments, we evaluated the effects of
      acute administration of caffeine on food consumption under different access
      conditions. CD1 male adult mice had access to highly palatable food (50% sucrose)
      in a restricted but habitual context, under continuous or intermittent access as
      well as under anxiogenic, or effortful conditions. Caffeine (2.5-20.0 mg/kg)
      increased intake at the highest dose under familiar continuous and intermittent
      access. However, this high dose reduced food intake in the dark-light paradigm.
      In contrast, a dopamine-depleting agent, tetrabenazine (TBZ; 1.0-8.0 mg/kg) did
      not affect food intake in any of those experimental conditions. In the T-maze
      barrier task that evaluates seeking and taking of food under effortful
      conditions, caffeine (10.0 mg/kg) decreased latency to reach the food, but did
      not affect selection of the high-food density arm that required more effort, or
      the total amount of food consumed. In contrast, TBZ (4.0 mg/kg) reduced selection
      of the high food density arm with the barrier, thus affecting amount of food
      consumed. Interestingly, a small dose of caffeine (5.0 mg/kg) was able to reverse
      the anergia-inducing effects produced by TBZ in the T-maze. These results suggest
      that caffeine can potentiate or suppress food consumption depending on the
      context. Moreover, caffeine did not change appetite, and did not impair
      orientation toward food under effortful conditions, but it rather helped to
      achieve the goal by improving speed and by reversing performance to normal levels
      when fatigue was induced by dopamine depletion.

PMID- 30237773
TI  - Is Attention Really Effort? Revisiting Daniel Kahneman's Influential 1973 Book
      Attention and Effort.
AB  - Daniel Kahneman was not the first to suggest that attention and effort are
      closely associated, but his 1973 book Attention and Effort, which claimed that
      attention can be identified with effort, cemented the association as a research
      paradigm in the cognitive sciences. Since then, the paradigm has rarely been
      questioned and appears to have set the research agenda so that it is self
      reinforcing. In this article, we retrace Kahneman's argument to understand its
      strengths and weaknesses. The central notion of effort is not clearly defined in
      the book, so we proceed by constructing the most secure inferences we can from
      Kahneman's argument regarding effort: it is cognitive, objective, metabolic
      expenditure, and it is attention. Continuing, we find from Kahneman's argument
      that effort-attention must be a special case of sympathetic dominance of the
      autonomic nervous system that is also an increase in metabolic activity in the
      brain that has crossed a threshold of magnitude. We then weigh this conception of
      effort against evidence in Kahneman's book and against more recent evidence,
      finding that it does not warrant the conclusion that effort can be equated with
      attention. In support of an alternative perspective, we briefly review diverse
      studies of behavior, physiology, and neuroscience on attention and effort,
      including meditation and studies of the LC-NE system, where we find evidence for
      the following: (1) Attention seems to be associated not with the utilization of
      metabolic resources per se but with the readying of metabolic resources in the
      form of adaptive gain modulation. This occurs under sympathetic dominance and can
      be experienced as effortful. (2) Attention can also occur under parasympathetic
      dominance, in which case it is likely to be experienced as effortless.

PMID- 30237774
TI  - The Influence of Self-Control and Social Status on Self-Deception.
AB  - The purpose of this study was to explore the effects of self-control and social
      status on self-deception. The present study adopted a forward-looking paradigm to
      investigate how self-control and social status influence self-deception. In
      Experiment 1, participants were asked to complete 10 questions, after they
      predicted and completed 40 questions (commonsense judgment materials) either with
      or without answer hints. The results indicated that the participants had higher
      predicted scores under conditions with answer hints compared with conditions
      without answer hints and that the predicted scores were much higher than the
      actual scores under conditions with answer hints. In Experiment 2, individuals
      with different self-control traits were chosen to perform the operation and
      induction of the perception of social status and then complete tests such as
      Experiment 1. The results showed that differences in the predicted scores between
      conditions with answer hints and those without answer hints were observed to be
      greater in individuals with low self-control traits than in individuals with
      higher self-control traits, however, such differences between individuals with
      higher and low self-control traits were only observed in conditions with low
      social status perception, not in the conditions with high social status
      perception. The findings indicated that compared with individuals with high self
      control, low self-control individuals tended to produce more self-deception. In
      addition, high social status in the individuals' perception could restrain the
      influence of low self-control on self-deception, while low social status in the
      individuals' perception could increase the self-control's influence on self
      deception.

PMID- 30237775
TI  - When Everyone Wins? Exploring Employee and Customer Preferences for No-Haggle
      Pricing.
AB  - The organizational importance for interactions between frontline employees and
      customers has been examined in relation to dimensions such as climate or culture.
      In this article, we highlight the importance of pricing strategies - typically
      studied in relation to consumer preferences - for frontline employees. To do
      this, we apply an evolutionary perspective and present two complementary studies
      that focus on the relevance of price discipline in relation to employee attitudes
      and preferences. Focusing on the industry of new automobile sales since there is
      important firm-level pricing variation, Study 1 finds a faintly positive
      relationship among employee prosociality, customer satisfaction, and fixed or "no
      haggle" pricing strategies. In Study 2, participants indicated a preference for
      working in environments that offered the same, non-disparate prices to all
      customers. While previous research has examined the relationships between
      employee and customer attitudes in relation to firm performance, our studies
      emphasize the role that pricing strategies can play as a mechanism in those
      relationships. Our studies illustrate the value of evolutionary frameworks for
      contemporary business problems.

PMID- 30237776
TI  - The Role of Character Strengths in Depression: A Structural Equation Model.
AB  - The main aim of present study was to develop a model that specifies the
      predictive effects of some character strengths in depression. Two hundred
      individuals with major depression were recruited from clinical psychology
      centers. Participants completed a battery of questionnaires measuring
      dysfunctional attitudes, basic emotions, character strengths, and depression.
      Seven character strengths of critical thinking, emotional intelligence,
      gratitude, forgiveness, hope, spirituality, and zest were selected to measure the
      latent variable of character strengths. Structural equation modeling was used to
      analyze the data. Normed chi-square, comparative fit index, incremental fit
      index, and other indices demonstrated an adequate fit for the model suggesting
      that character strengths had an indirect effect on depression through the
      mediation of dysfunctional attitudes, negative affect, and happiness. Character
      strengths had negative effects on dysfunctional attitudes and positive effects on
      happiness. The findings of present study have implications for practitioners and
      researchers to develop an integrative model for the treatment of depression.

PMID- 30237777
TI  - Challenges and Solutions Perceived by Educators in an Early Childcare Program for
      Refugee Children.
AB  - Immigration to Germany peaked in 2016. More than 105,000 refugees below the age
      of 7 years arrived within 12 months. Since then, Germany and other host nations
      have been in need of strategies to cover the emerging demand for childcare
      services. The German federal state North-Rhine Westphalia has funded a
      specialized early childhood education and care (ECEC) program for recently
      arrived refugees. The present study investigated challenges and possible
      solutions in this specialized ECEC. In a pilot study, inductive content analysis
      of n1 = 28 semi-structured interviews with early childhood educators revealed 19
      distinct challenges and four generic categories for solutions (provide clear and
      predictable structures, involve and support parents, ensure adequate structural
      features of the childcare group, convey trust and feelings of competence). For
      the main study, identified challenges were transcribed into items for a closed
      format questionnaire, which was distributed to a second sample of educators (n2 =
      96). Challenges perceived as most difficult concerned language barriers and
      communication with parents. An exploratory factor analysis of the challenges
      questionnaire yielded four underlying domains (interpersonal stress, feasibility
      and attendance, cultural and communication barriers, structural features of a
      childcare group). Our study provides a first basis to adapt childcare settings
      for refugees, and to guide staff training for this special group. We discuss
      evidence in regard to understanding how ECEC programs can successfully promote
      refugee children's psychosocial adaptation and educational outcomes.

PMID- 30237779
TI  - Perceptions of Economic Inequality in Colombian Daily Life: More Than Unequal
      Distribution of Economic Resources.
AB  - Research on perceptions of economic inequality focuses on estimations of the
      distribution of financial resources, such as perceived income gaps or wealth
      distribution. However, we argue that perceiving inequality is not limited to an
      economic idea but also includes other dimensions related to people's daily life.
      We explored this idea by conducting an online survey (N = 601) in Colombia, where
      participants responded to an open-ended question regarding how they perceived
      economic inequality. We performed a content analysis of 1,624 responses to
      identify relevant topics and used network analysis tools to explore how such
      topics were interrelated. We found that perceived economic inequality is mainly
      represented by identifying social classes (e.g., the elites vs. the poor),
      intergroup relations based on discrimination and social exclusion, public spaces
      (e.g., beggars on streets, spatial segregation), and some dynamics about the
      distribution of economic resources and the quality of work (e.g., income
      inequality, precarious jobs). We discuss how different perceptions of economic
      inequality may frame how people understand and respond to inequality.

PMID- 30237780
TI  - Editorial: Problem Gambling: Summarizing Research Findings and Defining New
      Horizons.

PMID- 30237778
TI  - Functional Neuroanatomy of Second Language Sentence Comprehension: An fMRI Study
      of Late Learners of American Sign Language.
AB  - The neurobiology of sentence comprehension is well-studied but the properties and
      characteristics of sentence processing networks remain unclear and highly
      debated. Sign languages (i.e., visual-manual languages), like spoken languages,
      have complex grammatical structures and thus can provide valuable insights into
      the specificity and function of brain regions supporting sentence comprehension.
      The present study aims to characterize how these well-studied spoken language
      networks can adapt in adults to be responsive to sign language sentences, which
      contain combinatorial semantic and syntactic visual-spatial linguistic
      information. Twenty native English-speaking undergraduates who had completed
      introductory American Sign Language (ASL) courses viewed videos of the following
      conditions during fMRI acquisition: signed sentences, signed word lists, English
      sentences and English word lists. Overall our results indicate that native
      language (L1) sentence processing resources are responsive to ASL sentence
      structures in late L2 learners, but that certain L1 sentence processing regions
      respond differently to L2 ASL sentences, likely due to the nature of their
      contribution to language comprehension. For example, L1 sentence regions in
      Broca's area were significantly more responsive to L2 than L1 sentences,
      supporting the hypothesis that Broca's area contributes to sentence comprehension
      as a cognitive resource when increased processing is required. Anterior temporal
      L1 sentence regions were sensitive to L2 ASL sentence structure, but demonstrated
      no significant differences in activation to L1 than L2, suggesting its
      contribution to sentence processing is modality-independent. Posterior superior
      temporal L1 sentence regions also responded to ASL sentence structure but were
      more activated by English than ASL sentences. An exploratory analysis of the
      neural correlates of L2 ASL proficiency indicates that ASL proficiency is
      positively correlated with increased activations in response to ASL sentences in
      L1 sentence processing regions. Overall these results suggest that well
      established fronto-temporal spoken language networks involved in sentence
      processing exhibit functional plasticity with late L2 ASL exposure, and thus are
      adaptable to syntactic structures widely different than those in an individual's
      native language. Our findings also provide valuable insights into the unique
      contributions of the inferior frontal and superior temporal regions that are
      frequently implicated in sentence comprehension but whose exact roles remain
      highly debated.

PMID- 30237781
TI  - Interactions Elicited by the Contradiction Between Figure Direction
      Discrimination and Figure-Ground Segregation.
AB  - Figure-ground (FG) segregation that separates an object from the rest of the
      image is a fundamental problem in vision science. A majority of neurons in monkey
      V2 showed the selectivity to border ownership (BO) that indicates which side of a
      contour owns the border. Although BO could be a precursor of FG segregation, the
      contribution of BO to FG segregation has not been clarified. Because FG
      segregation is the perception of the global region that belongs to an object,
      whereas BO determination provides the local direction of figure (DOF) along a
      contour, a spatial integration of BO might be expected for the generation of FG.
      To understand the mechanisms underlying the perception of figural regions, we
      investigated the interaction between the local BO determination and the global FG
      segregation through the quantitative analysis of the visual perception and the
      spatiotemporal characteristics of eye movements. We generated a set of novel
      stimuli in which translucency induces local DOF along the contour and global FG
      independently so that DOF and FG could be either consistent or contradictory. The
      perceptual responses showed better performance in DOF discrimination than FG
      segregation, supporting distinct mechanisms for the DOF discrimination and the FG
      segregation. We examined whether the contradiction between DOF and FG modulates
      the eye movement while participants judged DOF and FG. The duration of the first
      eye fixation was modulated by the contradiction during FG segregation but not DOF
      discrimination, suggesting a sequential processing from the BO determination to
      the FG segregation. These results of human perception and eye fixation provide
      important clues for understanding the visual processing for FG segregation.

PMID- 30237782
TI  - Growth Hormone Deficiency Is Frequent After Recent Stroke.
AB  - Introduction: The incidence of pituitary dysfunction after severe ischemic stroke
      is unknown, however given the increasing attention to pituitary dysfunction after
      neurological injuries such as traumatic brain injury, this may represent a novel
      area of research in stroke. Methods: We perform an arginine and human growth
      hormone releasing hormone challenge on ischemic stroke patients within a week of
      symptom onset. Results: Over the study period, 13 patients were successfully
      tested within a week of stroke (baseline NIHSS 10, range 7-16). Overall, 9(69%)
      patients had a poor response, with 7(54%) of these patients meeting the criteria
      for had human growth hormone deficiency. Other measures of pituitary function
      were within normal ranges. Conclusion: After major ischemic stroke, low GH levels
      are common and may play a role in stroke recovery.

PMID- 30237783
TI  - Functional and Structural Brain Damage in Friedreich's Ataxia.
AB  - Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder caused
      by a GAA repeat expansion in the FXN gene. There is still no cure or quantitative
      biomarkers reliaby correlating with the progression rate and disease severity.
      Investigation of functional and structural alterations characterizing white (WM)
      and gray matter (GM) in FRDA are needed prerequisite to monitor progression and
      response to treatment. Here we report the results of a multimodal cross-sectional
      MRI study of FRDA including Voxel-Based Morphometry (VBM), diffusion-tensor
      imaging (DTI), functional MRI (fMRI), and a correlation analysis with clinical
      severity scores. Twenty-one early-onset FRDA patients and 18 age-matched healthy
      controls (HCs) were imaged at 3T. All patients underwent a complete cognitive and
      clinical assessment with ataxia scales. VBM analysis showed GM volume reduction
      in FRDA compared to HCs bilaterally in lobules V, VI, VIII (L>R), as well as in
      the crus of cerebellum, posterior lobe of the vermis, in the flocculi and in the
      left tonsil. Voxel-wise DTI analysis showed a diffuse fractional anisotropy
      reduction and mean, radial, axial (AD) diffusivity increase in both
      infratentorial and supratentorial WM. ROI-based analysis confirmed the results
      showing differences of the same DTI metrics in cortico-spinal-tracts, forceps
      major, corpus callosum, posterior thalamic radiations, cerebellar penduncles.
      Additionally, we observed increased AD in superior (SCP) and middle cerebellar
      peduncles. The WM findings correlated with age at onset (AAO), short-allelle GAA,
      and disease severity. The intragroup analysis of fMRI data from right-handed 14
      FRDA and 15 HCs showed similar findings in both groups, including activation in
      M1, insula and superior cerebellar hemisphere (lobules V-VIII). Significant
      differences emerged only during the non-dominant hand movement, with HCs showing
      a stronger activation in the left superior cerebellar hemisphere compared to
      FRDA. Significant correlations were found between AAO and the fMRI activation in
      cerebellar anterior and posterior lobes, insula and temporal lobe. Our multimodal
      neuroimaging protocol suggests that MRI is a useful tool to document the
      extension of the neurological impairment in FRDA.

PMID- 30237784
TI  - The Stochastic Entanglement and Phantom Motor Execution Hypotheses: A Theoretical
      Framework for the Origin and Treatment of Phantom Limb Pain.
AB  - Phantom limb pain (PLP) is a debilitating condition common after amputation that
      can considerably hinder patients' quality of life. Several treatments have
      reported promising results in alleviating PLP. However, clinical evaluations are
      usually performed in small cohorts and rigorous clinical trials are scarce. In
      addition, the underlying mechanisms by which novel interventions alleviate PLP
      are often unclear, potentially because the condition itself is poorly understood.
      This article presents a theoretical framework of PLP that can be used as
      groundwork for hypotheses of novel treatments. Current hypotheses on the origins
      of PLP are discussed in relation to available clinical findings. Stochastic
      entanglement of the pain neurosignature, or connectome, with impaired
      sensorimotor circuitry is proposed as an alternative hypothesis for the genesis
      of PLP, and the implications and predictions this hypothesis entails are
      examined. In addition, I present a hypothesis for the working mechanism of
      Phantom Motor Execution (PME) as a treatment of PLP, along with its relation to
      the aforementioned stochastic entanglement hypothesis, which deals with PLP's
      incipience. PME aims to reactivate the original central and peripheral circuitry
      involved in motor control of the missing limb, along with increasing dexterity of
      stump muscles. The PME hypothesis entails that training of phantom movements
      induces gradual neural changes similar to those of perfecting a motor skill, and
      these purposefully induced neural changes disentangle pain processing circuitry
      by competitive plasticity. This is a testable hypothesis that can be examined by
      brain imaging and behavioral studies on subjects undergoing PME treatment. The
      proposed stochastic entanglement hypothesis of PLP can be generalized to
      neuropathic pain due to sensorimotor impairment, and can be used to design
      suitable therapeutic treatments.

PMID- 30237785
TI  - Advances and Unmet Needs in the Therapeutics of Bone Fragility.
AB  - The prevalence of fragility fractures increases as longevity increases the
      proportion of the elderly in the community. Until recently, the majority of
      studies have targeted women with osteoporosis defined as a bone mineral density
      (BMD) T score of < -2.5 SD, despite evidence that the population burden of
      fractures arises from women with osteopenia. Antiresorptive agents reduce
      vertebral and hip fracture risk by ~50 percent during 3 years but efficacy
      against non-vertebral fractures, 80% of all fractures in the community, is
      reported in few studies, and of those, the risk reduction is only 20-30%. Recent
      advances in the use of antiresorptives and anabolic agents has addressed some of
      these unmet needs. Zoledronic acid is now reported to reduce vertebral and non
      vertebral fractures rates in women with osteopenia. Studies using teriparatide
      demonstrate better vertebral and clinical (symptomatic vertebral and non
      vertebral) antifracture efficacy than risedronate. Abaloparatide, a peptide
      sharing amino acid sequences with teriparatide, reduces vertebral and non
      vertebral fractures. Romosozumab, a monoclonal antibody suppressing sclerostin,
      reduces vertebral and non-vertebral fractures within a year of starting
      treatment, and does so more greatly than alendronate. Some recent studies signal
      undesirable effects of therapy but provide essential cautionary insights into
      long term management. Cessation of denosumab is associated with a rapid increase
      in bone remodeling and the uncommon but clinically important observation of
      increased multiple vertebral fractures suggesting the need to start alternative
      anti-resorptive therapy around the time of stopping denosumab. Antiresorptives
      like bisphosphonates and denosumab suppress remodeling but not completely.
      Antifracture efficacy may be limited, in part, as a consequence of continued
      unsuppressed remodeling, particularly in cortical bone. Bisphosphonates may not
      distribute in deeper cortical bone, so unbalanced intracortical remodeling
      continues to cause microstructural deterioration. In addition, suppressed
      remodeling may compromise the material composition by increasing matrix mineral
      density and glycosylation of collagen. As antiresorptive agents do not restore
      microstructural deterioration existing at the time of starting treatment, under
      some circumstances, anabolic therapy may be more appropriate first line
      treatment. Combining antiresorptive and anabolic therapy is an alternative but
      whether anti-fracture efficacy is greater than that achieved by either treatment
      alone is not known.

PMID- 30237786
TI  - Real Talk: The Inter-play Between the mTOR, AMPK, and Hexosamine Biosynthetic
      Pathways in Cell Signaling.
AB  - O-linked N-acetylglucosamine, better known as O-GlcNAc, is a sugar post
      translational modification participating in a diverse range of cell functions.
      Disruptions in the cycling of O-GlcNAc mediated by O-GlcNAc transferase (OGT) and
      O-GlcNAcase (OGA), respectively, is a driving force for aberrant cell signaling
      in disease pathologies, such as diabetes, obesity, Alzheimer's disease, and
      cancer. Production of UDP-GlcNAc, the metabolic substrate for OGT, by the
      Hexosamine Biosynthetic Pathway (HBP) is controlled by the input of amino acids,
      fats, and nucleic acids, making O-GlcNAc a key nutrient-sensor for fluctuations
      in these macromolecules. The mammalian target of rapamycin (mTOR) and AMP
      activated protein kinase (AMPK) pathways also participate in nutrient-sensing as
      a means of controlling cell activity and are significant factors in a variety of
      pathologies. Research into the individual nutrient-sensitivities of the HBP,
      AMPK, and mTOR pathways has revealed a complex regulatory dynamic, where their
      unique responses to macromolecule levels coordinate cell behavior. Importantly,
      cross-talk between these pathways fine-tunes the cellular response to nutrients.
      Strong evidence demonstrates that AMPK negatively regulates the mTOR pathway, but
      O-GlcNAcylation of AMPK lowers enzymatic activity and promotes growth. On the
      other hand, AMPK can phosphorylate OGT leading to changes in OGT function.
      Complex sets of interactions between the HBP, AMPK, and mTOR pathways integrate
      nutritional signals to respond to changes in the environment. In particular,
      examining these relationships using systems biology approaches might prove a
      useful method of exploring the complex nature of cell signaling. Overall,
      understanding the complex interactions of these nutrient pathways will provide
      novel mechanistic information into how nutrients influence health and disease.

PMID- 30237787
TI  - The Changing Face of Water: A Dynamic Reflection of Antibiotic Resistance Across
      Landscapes.
AB  - Little is known about the role of surface water in the propagation of antibiotic
      resistance (AR), or the relationship between AR and water quality declines. While
      healthcare and agricultural sectors are considered the main contributors to AR
      dissemination, few studies have been conducted in their absence. Using linear
      models and Bayesian kriging, we evaluate AR among Escherichia coli water isolates
      collected bimonthly from the Chobe River in Northern Botswana (n = 1997, n = 414
      water samples; July 2011-May 2012) in relation to water quality dynamics (E.
      coli, fecal coliform, and total suspended solids), land use, season, and AR in
      wildlife and humans within this system. No commercial agricultural or large
      medical facilities exist within this region. Here, we identify widespread AR in
      surface water, with land use and season significant predicators of AR levels.
      Mean AR was significantly higher in the wet season than the dry season (p =
      0.003), and highest in the urban landscape (2.15, SD = 0.098) than the protected
      landscape (1.39, SD = 0.051). In-water E. coli concentrations were significantly
      positively associated with mean AR in the wet season (p < 0.001) but not in the
      dry season (p = 0.110), with TSS negatively associated with mean AR across
      seasons (p = 0.016 and p = 0.029), identifying temporal and spatial relationships
      between water quality variables and AR. Importantly, when human, water, and
      wildlife isolates were examined, similar AR profiles were identified (p < 0.001).
      Our results suggest that direct human inputs are sufficient for extensive
      dispersal of AR into the environment, with landscape features, season, and water
      quality variables influencing AR dynamics. Focused and expensive efforts to
      minimize pollution from agricultural sources, while important, may only provide
      incremental benefits to the management of AR across complex landscapes.
      Controlling direct human AR inputs into the environment remains a critical and
      pressing challenge.

PMID- 30237789
TI  - Commentary: Phylogenomics and Comparative Genomic Studies Robustly Support
      Division of the Genus Mycobacterium into an Emended Genus Mycobacterium and Four
      Novel Genera.

PMID- 30237790
TI  - Molecular Networking-Based Metabolome and Bioactivity Analyses of Marine-Adapted
      Fungi Co-cultivated With Phytopathogens.
AB  - Fungi represent a rich source of bioactive metabolites and some are marketed as
      alternatives to synthetic agrochemicals against plant pathogens. However, the
      culturability of fungal strains in artificial laboratory conditions is still
      limited and the standard mono-cultures do not reflect their full spectrum
      chemical diversity. Phytopathogenic fungi and bacteria have successfully been
      used in the activation of cryptic biosynthetic pathways to promote the production
      of new secondary metabolites in co-culture experiments. The aim of this study was
      to map the fungal diversity of Windebyer Noor, a brackish lake connected to
      Baltic Sea (Germany), to induce the chemical space of the isolated marine-adapted
      fungi by co-culturing with phytopathogens, and to assess their inhibitory
      potential against six commercially important phytopathogens. Out of 123 marine
      adapted fungal isolates obtained, 21 were selected based on their phylogenetic
      and metabolite diversity. They were challenged with two phytopathogenic bacteria
      (Pseudomonas syringae and Ralstonia solanacearum) and two phytopathogenic fungi
      (Magnaporthe oryzae and Botrytis cinerea) on solid agar. An in-depth untargeted
      metabolomics approach incorporating UPLC-QToF-HRMS/MS-based molecular networking
      (MN), in silico MS/MS databases, and manual dereplication was employed for
      comparative analysis of the extracts belonging to nine most bioactive co-cultures
      and their respective mono-cultures. The phytopathogens triggered interspecies
      chemical communications with marine-adapted fungi, leading to the production of
      new compounds and enhanced expression of known metabolites in co-cultures. MN
      successfully generated a detailed map of the chemical inventory of both mono- and
      co-cultures. We annotated overall 18 molecular clusters (belonging to terpenes,
      alkaloids, peptides, and polyketides), 9 of which were exclusively produced in co
      cultures. Several clusters contained compounds, which could not be annotated to
      any known compounds, suggesting that they are putatively new metabolites. Direct
      antagonistic effects of the marine-adapted fungi on the phytopathogens were
      observed and anti-phytopathogenic activity was demonstrated.The untargeted
      metabolomics approach combined with bioactivity testing allowed prioritization of
      two co-cultures for purification and characterization of marine fungal
      metabolites with crop-protective activity. To our knowledge, this is the first
      study employing plant pathogens to challenge marine-adapted fungi.

PMID- 30237791
TI  - A Phylogenomic Study of Acanthamoeba polyphaga Draft Genome Sequences Suggests
      Genetic Exchanges With Giant Viruses.
AB  - Acanthamoeba are ubiquitous phagocytes predominant in soil and water which can
      ingest many microbes. Giant viruses of amoebae are listed among the Acanthamoeba
      resisting microorganisms. Their sympatric lifestyle within amoebae is suspected
      to promote lateral nucleotide sequence transfers. Some Acanthamoeba species have
      shown differences in their susceptibility to giant viruses. Until recently, only
      the genome of a single Acanthamoeba castellanii Neff was available. We analyzed
      the draft genome sequences of Acanthamoeba polyphaga through several approaches,
      including comparative genomics, phylogeny, and sequence networks, with the aim of
      detecting putative nucleotide sequence exchanges with giant viruses. We
      identified a putative sequence trafficking between this Acanthamoeba species and
      giant viruses, with 366 genes best matching with viral genes. Among viruses,
      Pandoraviruses provided the greatest number of best hits with 117 (32%) for A.
      polyphaga. Then, genes from mimiviruses, Mollivirus sibericum, marseilleviruses,
      and Pithovirus sibericum were best hits in 67 (18%), 35 (9%), 24 (7%), and 2
      (0.5%) cases, respectively. Phylogenetic reconstructions showed in a few cases
      that the most parsimonious evolutionary scenarios were a transfer of gene
      sequences from giant viruses to A. polyphaga. Nevertheless, in most cases,
      phylogenies were inconclusive regarding the sense of the sequence flow. The
      number and nature of putative nucleotide sequence transfers between A. polyphaga,
      and A. castellanii ATCC 50370 on the one hand, and pandoraviruses, mimiviruses
      and marseilleviruses on the other hand were analyzed. The results showed a lower
      number of differences within the same giant viral family compared to between
      different giant virus families. The evolution of 10 scaffolds that were
      identified among the 14 Acanthamoeba sp. draft genome sequences and that harbored
      >= 3 genes best matching with viruses showed a conservation of these scaffolds
      and their 46 viral genes in A. polyphaga, A. castellanii ATCC 50370 and A.
      pearcei. In contrast, the number of conserved genes decreased for other
      Acanthamoeba species, and none of these 46 genes were present in three of them.
      Overall, this work opens up several potential avenues for future studies on the
      interactions between Acanthamoeba species and giant viruses.

PMID- 30237792
TI  - Advantages of Using Blend Cultures of Native L. plantarum and O. oeni Strains to
      Induce Malolactic Fermentation of Patagonian Malbec Wine.
AB  - The malolactic fermentation (MLF) of Patagonian Malbec wine inoculated with blend
      cultures of selected native strains of Lactobacillus plantarum and Oenococcus
      oeni was monitored during 14 days, analyzing the strains ability to modify the
      content of some organic acids and to change the volatile compounds profile. The
      performance of the LAB strains was tested as single and blends cultures of both
      species. An implantation control by RAPD PCR was also carried out to
      differentiate among indigenous and inoculated strains. The L. plantarum strains
      UNQLp11 and UNQLp155 and the O. oeni strain UNQOe73.2 were able to remain viable
      during the monitoring time of MLF, whereas the O. oeni strain UNQOe31b showed a
      decrease of five log CFU at day 14. The four strains assayed showed a similar
      behavior in wine whether they were inoculated individually or as blend cultures.
      All strains were able to consume L-malic acid, particularly the L. plantarum
      strains, which showed the highest consumption values at day 14, both as single or
      blend cultures. The changes in the volatile compounds profile of Malbec wine
      samples, before and after MLF, were determined by HS-SPME and GC-MS technique.
      Wines inoculated with blend cultures containing strain UNQLp155 showed a decrease
      in the total alcohols content and an increase in the total esters content. On the
      other hand, wines inoculated with single cultures of strains UNQLp155, UNQOe31b
      or UNQOe73.2 showed no significant decrease in the total alcohols concentration
      but a significant increase in the total esters content. When strain UNQLp11 was
      inoculated as single or as blend culture with strain UNQOe31b, wines exhibited an
      increase in the total alcohols content, and a decrease in the total esters
      content. The content of diethyl succinate showed the greatest increase at final
      of MLF, and a particular synergistic effect in its synthesis was observed with a
      blend culture of strains UNQLp155 and UNQOe73.2. These results suggest that the
      use of blend cultures formulated with strains belonging to L. plantarum and O.
      oeni species could offer an interesting advantage to induce MLF in Malbec wines,
      contributing to diversify their aromatic profiles.

PMID- 30237793
TI  - Deciphering the Anode-Enhanced Azo Dye Degradation in Anaerobic Baffled Reactors
      Integrating With Microbial Fuel Cells.
AB  - Microbial anode respiration in microbial fuel cells (MFCs) can enhance the
      degradations of many electron acceptor-type contaminants which are presumed to be
      competitive to anode respiration. The mechanisms underlying those
      counterintuitive processes are important for MFCs application but are unclear.
      This study integrated MFCs with anaerobic baffled reactor (ABR), termed MFC-ABR,
      to enhance the reduction of azo dye acid orange-7 (AO-7). Compare with ABR, MFC
      ABR enhanced the degradation of AO-7, especially at high AO-7 concentration (800
      mg/L). Acute toxicity test suggested a higher detoxication efficiency in MFC-ABR.
      Higher microbial viability, dehydrogenase activity and larger sludge granule size
      were also observed in MFC-ABR. MFC-ABR significantly enriched and reshaped the
      microbial communities relative to ABR. Bacteria with respiratory versatility,
      e.g., Pseudomonas, Geobacter, and Shewanella, were significantly enriched.
      Functional prediction showed that six metabolism functions (manganese-, iron-,
      fumarate- and nitrate-respiration, oil bioremediation and chemoheterotrophy) were
      significantly stimulated while methanogenesis, sulfate-respiration, hydrogen
      oxidation were suppressed in MFC-ABR relative to ABR. The results provided
      important information for understanding the role of microbial anode respiration
      in contaminated environments.

PMID- 30237788
TI  - A Comprehensive Review on Equine Influenza Virus: Etiology, Epidemiology,
      Pathobiology, Advances in Developing Diagnostics, Vaccines, and Control
      Strategies.
AB  - Among all the emerging and re-emerging animal diseases, influenza group is the
      prototype member associated with severe respiratory infections in wide host
      species. Wherein, Equine influenza (EI) is the main cause of respiratory illness
      in equines across globe and is caused by equine influenza A virus (EIV-A) which
      has impacted the equine industry internationally due to high morbidity and
      marginal morality. The virus transmits easily by direct contact and inhalation
      making its spread global and leaving only limited areas untouched. Hitherto
      reports confirm that this virus crosses the species barriers and found to affect
      canines and few other animal species (cat and camel). EIV is continuously
      evolving with changes at the amino acid level wreaking the control program a
      tedious task. Until now, no natural EI origin infections have been reported
      explicitly in humans. Recent advances in the diagnostics have led to efficient
      surveillance and rapid detection of EIV infections at the onset of outbreaks.
      Incessant surveillance programs will aid in opting a better control strategy for
      this virus by updating the circulating vaccine strains. Recurrent vaccination
      failures against this virus due to antigenic drift and shift have been
      disappointing, however better understanding of the virus pathogenesis would make
      it easier to design effective vaccines predominantly targeting the conserved
      epitopes (HA glycoprotein). Additionally, the cold adapted and canarypox vectored
      vaccines are proving effective in ceasing the severity of disease. Furthermore,
      better understanding of its genetics and molecular biology will help in
      estimating the rate of evolution and occurrence of pandemics in future. Here, we
      highlight the advances occurred in understanding the etiology, epidemiology and
      pathobiology of EIV and a special focus is on designing and developing effective
      diagnostics, vaccines and control strategies for mitigating the emerging menace
      by EIV.

PMID- 30237795
TI  - Bacterial Communities in the Womb During Healthy Pregnancy.
AB  - The idea that healthy uterine cavity is sterile is challenged nowadays. It is
      still debatable whether the bacteria present in the uterine cavity during
      pregnancy are residents or invaders. To reveal microbiome composition and its
      characteristics in the womb of pregnant women, 41 decidual tissue samples and 64
      amniotic fluid samples were taken from pregnant Chinese women. DNA extraction was
      followed by pyrosequencing of the hypervariable V4 region of the 16S rDNA gene to
      characterize womb microbiome. Both types of samples had low diversity microbiome
      with Enterobacteriaceae being the dominant phylotypes at family level. To
      characterize the nature of colonization during pregnancy, the presence of
      endogenous biomass was confirmed by cultivation. Surprisingly, all of the 50
      amniotic fluid samples studied were culture-negative, whereas 379 out of 1,832
      placenta samples were culture-positive. Our results suggested that womb contained
      microbiome with low diversity. Culture-based investigation of amniotic fluid and
      placenta samples confirmed the presence of cultivable microorganisms in the
      placenta but not in amniotic fluid. Thus it suggests that bacterial colonization
      does occur during healthy pregnancy.

PMID- 30237794
TI  - Pull in and Push Out: Mechanisms of Horizontal Gene Transfer in Bacteria.
AB  - Horizontal gene transfer (HGT) plays an important role in bacterial evolution. It
      is well accepted that DNA is pulled/pushed into recipient cells by conserved
      membrane-associated DNA transport systems, which allow the entry of only single
      stranded DNA (ssDNA). However, recent studies have uncovered a new type of
      natural bacterial transformation in which double-stranded DNA (dsDNA) is taken up
      into the cytoplasm, thus complementing the existing methods of DNA transfer among
      bacteria. Regulated by the stationary-phase regulators RpoS and cAMP receptor
      protein (CRP), Escherichia coli establishes competence for natural transformation
      with dsDNA, which occurs in agar plates. To pass across the outer membrane, a
      putative channel, which may compete for the substrate with the porin OmpA, may
      mediate the transfer of exogenous dsDNA into the cell. To pass across the inner
      membrane, dsDNA may be bound to the periplasmic protein YdcS, which delivers it
      into the inner membrane channel formed by YdcV. The discovery of cell-to-cell
      contact-dependent plasmid transformation implies the presence of additional
      mechanism(s) of transformation. This review will summarize the current knowledge
      about mechanisms of HGT with an emphasis on recent progresses regarding non
      canonical mechanisms of natural transformation. Fully understanding the
      mechanisms of HGT will provide a foundation for monitoring and controlling
      multidrug resistance.

PMID- 30237796
TI  - Platelet Gene Therapy Promotes Targeted Peripheral Tolerance by Clonal Deletion
      and Induction of Antigen-Specific Regulatory T Cells.
AB  - Delivery of gene therapy as well as of biologic therapeutics is often hampered by
      the immune response of the subject receiving the therapy. We have reported that
      effective gene therapy for hemophilia utilizing platelets as a delivery vehicle
      engenders profound tolerance to the therapeutic product. In this study, we
      investigated whether this strategy can be applied to induce immune tolerance to a
      non-coagulant protein and explored the fundamental mechanism of immune tolerance
      induced by platelet-targeted gene delivery. We used ovalbumin (OVA) as a
      surrogate non-coagulant protein and constructed a lentiviral vector in which OVA
      is driven by the platelet-specific alphaIIb promoter. Platelet-specific OVA
      expression was introduced by bone marrow transduction and transplantation.
      Greater than 95% of OVA was stored in platelet alpha-granules. Control mice
      immunized with OVA generated OVA-specific IgG antibodies; however, mice
      expressing OVA in platelets did not. Furthermore, OVA expression in platelets was
      sufficient to prevent the rejection of skin grafts from CAG-OVA mice,
      demonstrating that immune tolerance developed in platelet-specific OVA-transduced
      recipients. To assess the mechanism(s) involved in this tolerance we used OTII
      mice that express CD4+ effector T cells specific for an OVA-derived peptide.
      After platelet-specific OVA gene transfer, these mice showed normal thymic
      maturation of the T cells ruling against central tolerance. In the periphery,
      tolerance involved elimination of OVA-specific CD4+ effector T cells by apoptosis
      and expansion of an OVA-specific regulatory T cell population. These experiments
      reveal the existence of natural peripheral tolerance processes to platelet
      granule contents which can be co-opted to deliver therapeutically important
      products.

PMID- 30237797
TI  - Dietary Supplementation With omega6 LC-PUFA-Rich Algae Modulates Zebrafish Immune
      Function and Improves Resistance to Streptococcal Infection.
AB  - Arachidonic acid (ARA, 20:4n-6) and dihomo-gamma-linolenic acid (DGLA, 20:3n-6)
      are omega-6 long-chain polyunsaturated fatty acids (LC-PUFA), which are key
      precursors for lipid mediators of the immune system and inflammatory response.
      The microalga Lobosphaera incisa (WT) and its Delta5-desaturase mutant P127 (MUT)
      are unique photosynthetic sources for ARA and DGLA, respectively. This study
      explores the effect of dietary supplementation with L. incisa and P127 biomass on
      tissue fatty acid composition, immune function, and disease resistance in
      zebrafish (Danio rerio). The broken microalgal biomass was added to commercial
      fish feed at 7.5 and 15% (w/w), providing 21.8 mg/g feed ARA for the WT
      supplemented group and 13.6 mg/g feed DGLA for the MUT-supplemented group at the
      15% inclusion levels. An unsupplemented group was used as the control. After 1
      month of feeding, fish were challenged with Streptococcus iniae. Fish were
      sampled before the challenge and 1 week after the challenge for various analyses.
      Tissue ARA and DGLA levels significantly increased in the liver, corresponding to
      microalgal supplementation levels. The elevated expression of specific immune
      related genes was evident in the kidneys in all treatment groups after 1 month of
      feeding, including genes related to eicosanoid synthesis, lysozyme, and NF
      kappaB. In the liver, microalgal supplementation led to the upregulation of genes
      related to immune function and antioxidant defense while the expression of
      examined genes involved in ARA metabolism was downregulated. Importantly, fish
      fed with 15% of both WT- and MUT-supplemented feed showed significantly (p <
      0.05) higher survival percentages (78 and 68%, respectively, as compared to only
      46% in the control group). The elevated expression of genes related to
      inflammatory and immune responses was evident post-challenge. Collectively, the
      results of the current study demonstrate the potential of microalgae-derived
      dietary ARA and DGLA in improving immune competence and resistance to bacterial
      infection in zebrafish as a model organism.

PMID- 30237798
TI  - Comparison of Protein and Peptide Targeting for the Development of a CD169-Based
      Vaccination Strategy Against Melanoma.
AB  - CD169+ macrophages are part of the innate immune system and capture pathogens
      that enter secondary lymphoid organs such as the spleen and the lymph nodes.
      Their strategic location in the marginal zone of the spleen and the subcapsular
      sinus in the lymph node enables them to capture antigens from the blood and the
      lymph respectively. Interestingly, these specific CD169+ macrophages do not
      destroy the antigens they obtain, but instead, transfer it to B cells and
      dendritic cells (DCs) which facilitates the induction of strong adaptive immune
      responses. This latter characteristic of the CD169+ macrophages can be exploited
      by specifically targeting tumor antigens to CD169+ macrophages for the induction
      of specific T cell immunity. In the current study we target protein and peptide
      antigen as antibody-antigen conjugates to CD169+ macrophages. We monitored the
      primary, memory, and recall T cell responses and evaluated the anti-tumor immune
      responses after immunization. In conclusion, both protein and peptide targeting
      to CD169 resulted in strong primary, memory, and recall T cell responses and
      protective immunity against melanoma, which indicates that both forms of antigen
      can be further explored as anti-cancer vaccination strategy.

PMID- 30237799
TI  - HIV-1 Viral Loads Are Not Elevated in Individuals Co-infected With Schistosoma
      spp. After Adjustment for Duration of HIV-1 Infection.
AB  - Studies of the role of Schistosoma co-infections on plasma HIV-1 RNA (HIV-1 viral
      load) have yielded incongruent results. The role of duration of HIV-1 infection
      on the link between Schistosoma and HIV-1 viral load has not been previously
      investigated. We aimed to assess the impact of HIV-1/Schistosoma co-infections on
      viral load in Antiretroviral Treatment (ART)-naive HIV-1 infected people taking
      into account the duration of HIV-1 infection. We describe 79 HIV-infected
      outpatients greater than 18 years of age who had never used ART in Mwanza,
      Tanzania. Schistosomiasis testing was done by urine and stool microscopy and by
      serum Schistosoma circulating anodic antigen (CAA) testing. Schistosoma
      positivity was defined as having either test positive. We conducted univariable
      and multivariable linear regressions to assess the relationship between
      Schistosoma infection and the log10 of viral load. Duration of HIV infection was
      calculated using the first measured CD4+ T-cell (CD4) count as a function of
      normal CD4 count decay per calendar year in drug naive individuals. An active
      Schistosoma infection was demonstrated in 46.8% of the patients. The median log10
      viral load was 4.5[3.4-4.9] log10 copies/mL in Schistosoma uninfected patients
      and 4.3[3.7-4.6] log10 copies/mL in Schistosoma infected patients. Schistosoma co
      infection was negatively associated with the log10 of viral load after adjustment
      for Schistosoma intensity as measured by CAA, CD4 counts at time of testing, and
      duration of HIV-1 infection (beta = -0.7[-1.3;-0.1], p = 0.022). Schistosoma co
      infection was not associated with viral load in univariable analysis. There was
      also no interaction between Schistosoma positivity and duration of HIV-1
      infection. Our study is the first, to our knowledge, to report adjustment for
      duration of HIV-1 infection when analyzing the relationship between HIV-1 viral
      load and Schistosoma spp. We found that time infected with HIV-1 has a major
      effect on the relationship between HIV-1 viral load and Schistosoma infection and
      may be a critical explanatory factor in the disparate findings of studies on HIV
      1 viral load and schistosomiasis. The log10 viral load difference found indicates
      that Schistosoma co-infection does not make HIV progression worse, and could
      possibly lead to slower HIV disease progression.

PMID- 30237800
TI  - Collectin-11 (CL-11) Is a Major Sentinel at Epithelial Surfaces and Key Pattern
      Recognition Molecule in Complement-Mediated Ischaemic Injury.
AB  - The complement system is a dynamic subset of the innate immune system, playing
      roles in host defense, clearance of immune complexes and cell debris, and priming
      the adaptive immune response. Over the last 40 years our understanding of the
      complement system has evolved from identifying its presence and recognizing its
      role in the blood to now focusing on understanding the role of local complement
      synthesis in health and disease. In particular, the local synthesis of complement
      was found to have an involvement in mediating ischaemic injury, including
      following transplantation. Recent work on elucidating the triggers of local
      complement synthesis and activation in renal tissue have led to the finding that
      Collectin-11 (CL-11) engages with L-fucose at the site of ischaemic stress,
      namely at the surface of the proximal tubular epithelial cells. What remains
      unknown is the precise structure of the damage-associated ligand that
      participates in CL-11 binding and subsequent complement activation. In this
      article, we will discuss our hypothesis regarding the role of CL-11 as an
      integral tissue-based pattern recognition molecule which we postulate has a
      significant contributory role in complement-mediated ischaemic injury.

PMID- 30237801
TI  - Distinct Roles for Bruton's Tyrosine Kinase in B Cell Immune Synapse Formation.
AB  - Bruton's tyrosine kinase (Btk) has a key role in the signaling pathways of
      receptors essential for the B lymphocyte response. Given its implication in B
      cell-related immunodeficiencies, leukemias/lymphomas and autoimmunity, Btk is
      studied intensely and is a target for therapy. Here, using primary B cells from
      distinct mouse models and the pharmacological inhibitors ibrutinib and
      acalabrutinib, we report distinct roles for Btk in antigen-triggered immune
      synapse (IS) formation. Btk recruitment to the plasma membrane regulates the B
      cell ability to trigger IS formation as well as its appropriate molecular
      assembly; Btk shuttling/scaffold activities seem more relevant than the kinase
      function on that. Btk-kinase activity controls antigen accumulation at the IS
      through the PLCgamma2/Ca2+ axis. Impaired Btk membrane-recruitment or kinase
      function likewise alters antigen-triggered microtubule-organizing center (MTOC)
      polarization to the IS, B cell activation and proliferation. Data also show that,
      for B cell function, IS architecture is as important as the quantity of antigen
      that accumulates at the synapse.

PMID- 30237803
TI  - Constitutive Vagus Nerve Activation Modulates Immune Suppression in Sepsis
      Survivors.
AB  - Patients surviving a septic episode exhibit persistent immune impairment and
      increased mortality due to enhanced vulnerability to infections. In the present
      study, using the cecal ligation and puncture (CLP) model of polymicrobial sepsis,
      we addressed the hypothesis that altered vagus nerve activity contributes to
      immune impairment in sepsis survivors. CLP-surviving mice exhibited less TNFalpha
      in serum following administration of LPS, a surrogate for an infectious
      challenge, than control-operated (control) mice. To evaluate the role of the
      vagus nerve in the diminished response to LPS, mice were subjected to bilateral
      subdiaphragmatic vagotomy at 2 weeks post-CLP. CLP-surviving vagotomized mice
      exhibited increased serum and tissue TNFalpha levels in response to LPS-challenge
      compared to CLP-surviving, non-vagotomized mice. Moreover, vagus nerve
      stimulation in control mice diminished the LPS-induced TNFalpha responses while
      having no effect in CLP mice, suggesting constitutive activation of vagus nerve
      signaling in CLP-survivors. The percentage of splenic CD4+ ChAT-EGFP+ T cells
      that relay vagus signals to macrophages was increased in CLP-survivors compared
      to control mice, and vagotomy in CLP-survivors resulted in a reduced percentage
      of ChAT-EGFP+ cells. Moreover, CD4 knockout CLP-surviving mice exhibited an
      enhanced LPS-induced TNFalpha response compared to wild-type mice, supporting a
      functional role for CD4+ ChAT+ T cells in mediating inhibition of LPS-induced
      TNFalpha responses in CLP-survivors. Blockade of the cholinergic anti
      inflammatory pathway with methyllcaconitine, an alpha7 nicotinic acetylcholine
      receptor antagonist, restored LPS-induced TNFalpha responses in CLP-survivors.
      Our study demonstrates that the vagus nerve is constitutively active in CLP
      survivors and contributes to the immune impairment.

PMID- 30237805
TI  - Aphid Colonization Affects Potato Root Exudate Composition and the Hatching of a
      Soil Borne Pathogen.
AB  - Plants suffer multiple, simultaneous biotic threats from both above and below
      ground. These pests and/or pathogens are commonly studied on an individual basis
      and the effects of above-ground pests on below-ground pathogens are poorly
      defined. Root exudates from potato plants (Solanum tuberosum L.) were analyzed to
      characterize the top-down plant-mediated interactions between a phloem-sucking
      herbivore (Myzus persicae) and a sedentary, endoparasitic nematode (Globodera
      pallida). Increasing inocula of the aphid, M. persicae, reduced the root mass of
      potato plants. Exudates collected from these roots induced significantly lower
      hatching of second-stage juveniles from G. pallida eggs over a 28-day period,
      than those from uninfested control plants. Inhibition of hatch was significantly
      positively correlated with size of aphid inoculum. Diminished hatching was
      partially recovered after treatment with root exudate from uninfested potato
      plants indicating that the effect on hatching is reversible but cannot be fully
      recovered. Glucose and fructose content was reduced in root exudates from aphid
      infested potato plants compared to controls and these sugars were found to induce
      hatching of G. pallida, but not to the same degree as potato root exudates (PRE).
      Supplementing aphid-infested PRE with sugars did not recover the hatching
      potential of the treatment, suggesting that additional compounds play an
      important role in egg hatch. The first gene upregulated in the closely related
      potato cyst nematode Globodera rostochiensis post-exposure to host root exudate,
      Neprilysin-1, was confirmed to be upregulated in G. pallida cysts after exposure
      to PRE and was also upregulated by the sugar treatments. Significantly reduced
      upregulation of Gpa-nep-1 was observed in cysts treated with root exudates from
      potato plants infested with greater numbers of aphids. Our data suggest that
      aphid infestation of potato plants affects the composition of root exudates, with
      consequential effects on the hatching and gene expression of G. pallida eggs.
      This work shows that an above-ground pest can indirectly impact the rhizosphere
      and reveals secondary effects for control of an economically important below
      ground pathogen.

PMID- 30237802
TI  - Stress and Inflammation in Coronary Artery Disease: A Review
      Psychoneuroendocrineimmunology-Based.
AB  - Recent findings have deeply changed the current view of coronary heart disease,
      going beyond the simplistic model of atherosclerosis as a passive process
      involving cholesterol build-up in the subintimal space of the arteries until
      their final occlusion and/or thrombosis and instead focusing on the key roles of
      inflammation and the immune system in plaque formation and destabilization.
      Chronic inflammation is a typical hallmark of cardiac disease, worsening outcomes
      irrespective of serum cholesterol levels. Low-grade chronic inflammation
      correlates with higher incidence of several non-cardiac diseases, including
      depression, and chronic depression is now listed among the most important
      cardiovascular risk factors for poor prognosis among patients with myocardial
      infarction. In this review, we include recent evidence describing the immune and
      endocrine properties of the heart and their critical roles in acute ischaemic
      damage and in post-infarct myocardial remodeling. The importance of the central
      and autonomic regulation of cardiac functions, namely, the neuro-cardiac axis, is
      extensively explained, highlighting the roles of acute and chronic stress,
      circadian rhythms, emotions and the social environment in triggering acute
      cardiac events and worsening heart function and metabolism in chronic
      cardiovascular diseases. We have also included specific sections related to
      stress-induced myocardial ischaemia measurements and stress cardiomyopathy. The
      complex network of reciprocal interconnections between the heart and the main
      biological systems we have presented in this paper provides a new vision of
      cardiovascular science based on psychoneuroendocrineimmunology.

PMID- 30237806
TI  - Profiles of Endogenous Phytohormones Over the Course of Norway Spruce Somatic
      Embryogenesis.
AB  - Conifer somatic embryogenesis (SE) is a process driven by exogenously supplied
      plant growth regulators (PGRs). Exogenous PGRs and endogenous phytohormones
      trigger particular ontogenetic events. Complex mechanisms involving a number of
      endogenous phytohormones control the differentiation of cells and tissues, as
      well as the establishment of structures and organs. Most of the mechanisms and
      hormonal functions in the SE of conifers have not yet been described. With the
      aim to better understand these mechanisms, we provided detailed analysis of the
      spectrum of endogenous phytohormones over the course of SE in Norway spruce
      (Picea abies). Concentrations of endogenous phytohormones including auxins,
      cytokinins (CKs), abscisic acid (ABA), jasmonates, and salicylic acid (SA) in
      somatic P. abies embryos were analyzed by HPLC-ESI-MS/MS. The results revealed
      that the concentrations of particular phytohormone classes varied substantially
      between proliferation, maturation, desiccation, and germination. Endogenous ABA
      showed a maximum concentration at the maturation stage, which reflected the
      presence of exogenous ABA in the medium and demonstrated its efficient perception
      by the embryos as a prerequisite for their further development. Auxins also had
      concentration maxima at the maturation stage, suggesting a role in embryo
      polarization. Endogenous jasmonates were detected in conifer somatic embryos for
      the first time, and reached maxima at germination. According to our knowledge, we
      have presented evidence for the involvement of the non-indole auxin phenylacetic
      acid, cis-zeatin- and dihydrozeatin-type CKs and SA in SE for the first time. The
      presented results represent the currently most comprehensive overview of plant
      hormone levels in embryos throughout the whole process of conifer SE. The
      differences in concentrations of various classes of phytohormones over the
      proliferation, maturation, desiccation, and germination in somatic P. abies
      embryos clearly indicate correlations between endogenous phytohormone profiles
      and particular developmental stages of the SE of conifers.

PMID- 30237807
TI  - Chloroplast Protein 12 Expression Alters Growth and Chilling Tolerance in
      Tropical Forage Stylosanthes guianensis (Aublet) Sw.
AB  - Stylosanthes guianensis (Aublet) Sw. is a tropical forage legume with soil
      acidity tolerance and excellent adaptation to infertile soils, but sensitive to
      chilling. To understand the molecular responses of S. guianensis to chilling,
      differentially expressed genes between a chilling tolerant mutant 7-1 and the
      wild type were identified using suppression subtractive hybridization, and eight
      of them were confirmed and the regulation pattern were analyzed using
      quantitative reverse transcription PCR (qRT-PCR). Chloroplast protein 12 (CP12)
      functions to regulate the Calvin cycle by forming a ternary complex with
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK).
      SgCP12 transcript was induced by chilling in both plants, and higher levels were
      observed in 7-1 than in the wild type, implying a potential role of SgCP12 in
      chilling tolerance. To confirm this, transgenic S. guianensis plants over
      expressing or down-regulating SgCP12 were generated, respectively. Higher Fv/Fm
      and survival rate and lower ion leakage were observed in transgenic plants
      overexpressing SgCP12 as compared with the wild type after chilling treatment,
      while lower Fv/Fm and survival rate and higher ion leakage were found in SgCP12
      antisense plants. SgCP12 overexpression plants showed promoted growth with
      increased plant height and fresh weight, while the antisense plants exhibited
      reduced growth with decreased plant height and fresh weight as compared with the
      wild type. The results indicated that regulation of SgCP12 expression alters
      plant growth and chilling tolerance in S. guianensis. In addition, higher levels
      of net photosynthetic rate (Pn), GAPDH and PRK activities were observed in SgCP12
      overexpression transgenic plants, while lower levels in antisense plants than in
      the wild type under both control and chilling conditions, indicating that altered
      activities of GAPDH and PRK were associated with the changed Pn in transgenic S.
      guianensis. Our results suggest that SgCP12 regulates GAPDH and PRK activities,
      Pn, and chilling tolerance in S. guianensis.

PMID- 30237804
TI  - OsCER1 Plays a Pivotal Role in Very-Long-Chain Alkane Biosynthesis and Affects
      Plastid Development and Programmed Cell Death of Tapetum in Rice (Oryza sativa
      L.).
AB  - Cuticle waxes, which are primarily comprised of very-long-chain (VLC) alkanes,
      play an important role in plant reproductive development. ECERIFERUM1 (CER1) is
      recognized as the core element for VLC alkane biosynthesis in Arabidopsis
      (Arabidopsis thaliana). However, genes involved in the VLC alkane biosynthesis in
      rice remain unclear, and the alkane-form pathway in rice has still to be further
      explored. Here, we show that OsCER1, a homology of CER1, functions in VLC alkanes
      biosynthesis, which also could regulate anther development and plastids
      differentiation in rice. OsCER1 was highly expressed in the tapetum (stage 10)
      and bicellular pollen cells (stage 11). The decreased content of VLC alkanes (C25
      and C27) in the OsCER1 knocked down plants as well as the increased content of
      C27 alkanes in the OsCER1 overexpression plants indicates that OsCER1
      participates in VLC alkane biosynthesis. Downregulation of OsCER1 in rice led to
      sterility, and fewer amyloplasts within the mature pollen grains. In addition,
      the downregulation of OsCER1 in rice caused delayed tapetal programmed cell death
      and abnormal development of plastids in the tapetal cells. Furthermore,
      significantly altered levels of expression of genes involved in the pollen
      development were exhibited in the OsCER1 knocked down plants. These results
      indicate that OsCER1 is critical for VLC alkanes biosynthesis, plastids
      differentiation, and pollen development. This work provides insights into the VLC
      alkanes biosynthesis in anther development in rice.

PMID- 30237809
TI  - STATINS AND BONE HEALTH: A MINI REVIEW.
AB  - Statins are a widely prescribed class of medications that inhibit similar
      pathways as the anti-resorptive bisphosphonate drugs. Statins target the
      mevalonate pathway by blocking HMG-CoA reductase. Several recent meta-analyses
      concluded statins are osteoprotective in the general population. Here we present
      current literature exploring the mechanisms underlying the putative
      osteoprotective effects of statins. We also review recent clinical studies,
      ranging from observational cohort studies to randomized clinical trials, testing
      the effect of statins on bone health in various populations.

PMID- 30237808
TI  - Epigenome-Wide Analyses Identify Two Novel Associations With Recurrent Stroke in
      the Vitamin Intervention for Stroke Prevention Clinical Trial.
AB  - DNA methylation, a well-characterized epigenetic modification that is influenced
      by both environment and genetic variation, has previously been implicated in a
      number of complex diseases, including cardiovascular disease and stroke. The goal
      of this study was to evaluate epigenome-wide associations with recurrent stroke
      and the folate one-carbon metabolism-related trait, plasma homocysteine (hcy).
      Differential methylation analyses were performed on 473,864 autosomal CpG loci,
      using Illumina HumanMethylation 450K array data in 180 ischemic stroke cases from
      the Vitamin Intervention for Stroke Prevention (VISP) clinical trial. Linear
      regression was used to assess associations between number of strokes prior to
      VISP enrollment and measures of hcy with degree of methylation (beta-values),
      while logistic regression was used to evaluate recurrent stroke status and
      incident recurrent stroke associations. All regression analyses were stratified
      by race. Two differentially methylated CpG sites exceeded epigenome-wide
      significance (p <= 1.055 * 10-7) for prior number of strokes (PNS) in European
      Americans. The top locus, cg22812874, was located in the ankyrin repeat and SOCS
      box containing 10 gene (ASB10; p = 3.4 * 10-9; beta = -0.0308; 95% CI = -0.040, 
      0.002). Methylation locus cg00340919, located in an intron of the
      tetratricopeptide repeat domain 37 gene, was also statistically significant
      (TTC37; p = 8.74 * 10-8; beta = -0.0517; 95% CI = -0.069, -0.034). An additional
      138 CpG sites met our threshold for suggestive significance (p <= 5 * 10-5). We
      evaluated DNA methylation associated with recurrent stroke and hcy phenotypes
      across the epigenome. Hypermethylation at two CpG sites located in ASB10 and
      TTC37 was associated with fewer strokes prior to VISP enrollment. Our findings
      present a foundation for additional epigenome-wide studies, as well as
      mechanistic studies into epigenetic marks that influence recurrent stroke risk.

PMID- 30237810
TI  - Systematic identification of the key candidate genes in breast cancer stroma.
AB  - Background: Tumor microenvironment, in particular the stroma, plays an important
      role in breast cancer cell invasion and metastasis. Investigation of the
      molecular characteristics of breast cancer stroma may reveal targets for future
      study. Methods: The transcriptome profiles of breast cancer stroma and normal
      breast stroma were compared to identify differentially expressed genes (DEGs).
      The method was analysis of GSE26910 and GSE10797 datasets. Common DEGs were
      identified and then analyses of enriched pathways and hub genes were performed.
      Results: A total of 146 DEGs were common to GSE26910 and GSE10797. The enriched
      pathways were associated with "extracellular matrix (ECM) organization", "ECM
      receptor interaction" and "focal adhesion". Network analysis identified six key
      genes, including JUN, FOS, ATF3, STAT1, COL1A1 and FN1. Notably, COL1A1 and FN1
      were identified for the first time as cancer stromal key genes associated with
      breast cancer invasion and metastasis. Oncome analysis showed that the high
      expression levels of COL1A1 and FN1 correlated to an advanced stage of breast
      cancer and poor clinical outcomes. Conclusions: We found that several conserved
      tumor stromal genes might regulate breast cancer invasion through ECM remodeling.
      The clinical outcome analyses of COL1A1 and FN1 suggest these two genes are
      promising targets for future studies.

PMID- 30237811
TI  - Pre-implant magnetic resonance and transrectal ultrasound imaging in high-dose
      rate prostate brachytherapy: comparison of prostate volumes, craniocaudal
      extents, and contours.
AB  - Purpose: The purpose of this study was to compare the prostate contours drawn by
      two radiation oncologists and one radiologist on magnetic resonance (MR) and
      transrectal ultrasound (TRUS) images. TRUS intra- and inter-fraction variability
      as well as TRUS vs. MR inter-modality and inter-operator variability were
      studied. Material and methods: Thirty patients affected by localized prostate
      cancer and treated with interstitial high-dose-rate (HDR) prostate brachytherapy
      at the National Cancer Institute in Milan were included in this study. Twenty
      five patients received an exclusive two-fraction (14 Gy/fraction) treatment,
      while the other 5 received a single 14 Gy fraction as a boost after external beam
      radiotherapy. The prostate was contoured on TRUS images acquired before (virtual
      US) and after (real US) needle implant by two radiation oncologists, whereas on
      MR prostate was independently contoured by the same radiation oncologists (MR1,
      MR2) and by a dedicated radiologist (MR3). Absolute differences of prostate
      volumes (?DeltaV?) and craniocaudal extents (?Deltadz?) were evaluated. The
      Dice's coefficient (DC) was calculated to quantify spatial overlap between MR
      contours. Results: Significant difference was found between Vvirtual and Vlive (p
      < 0.001) for the first treatment fractions and between VMR1 and VMR2 (p = 0.043).
      Significant difference between cranio-caudal extents was found between dzvirtual
      and dzlive (p < 0.033) for the first treatment fractions, between dzvirtual of
      the first treatment fractions and dzMR1 (p < 0.001) and between dzMR1 and dzMR3
      (p < 0.01). Oedema might be responsible for some of the changes in US volumes.
      Average DC values resulting from the comparison MR1 vs. MR2, MR1 vs. MR3 and MR2
      vs. MR3 were 0.95 +/- 0.04 (range, 0.82-0.99), 0.87 +/- 0.04 (range, 0.73-0.91)
      and 0.87 +/- 0.04 (range, 0.72-0.91), respectively. Conclusions: Our results
      demonstrate the importance of a multiprofessional approach to TRUS-guided HDR
      prostate brachytherapy. Specific training in MR and US prostate imaging is
      recommended for centers that are unfamiliar with HDR prostate brachytherapy.

PMID- 30237812
TI  - Plan reproducibility of intraoperatively custom-built linked seeds compared to
      loose seeds for prostate brachytherapy.
AB  - Purpose: Few studies have compared the implant quality of linked and loose seeds
      for prostate brachytherapy. This study aimed to evaluate and compare plan
      reproducibility of intraoperatively built custom linked seeds and loose seeds for
      prostate brachytherapy. Material and methods: Between December 2010 and March
      2014, 76 localized prostate cancer patients received Iodine-125 brachytherapy
      with external beam radiotherapy. Linked and loose seeds were implanted in 39 and
      37 patients, respectively. The primary endpoint was the mean (+/- standard
      deviation) of the absolute change in the minimum dose received by 90% of the
      prostate volume between intraoperative and post-operative planning (DeltaD90) to
      confirm plan reproducibility. Comparisons between the groups were evaluated using
      2-sample t tests. Results: The DeltaD90 values were 6.95 +/- 11.6% and -0.41 +/-
      8.5% for the loose and linked seed groups, respectively (p < 0.01). The linked
      seed group showed decreased post-operative D90 (118.8% vs. 127.2%), V150 (51.7%
      vs. 66.7%), and RV100 (0.44 ml vs. 0.61 ml) compared to the loose seed group (p <
      0.01), whereas lung migration tended to be reduced (0% vs. 8%). Conclusions: The
      plan reproducibility of the linked seed group was better than that of the loose
      seed group. Moreover, the linked seed group showed less migration and lower
      rectal dose.

PMID- 30237813
TI  - Five-year effectiveness of low-dose-rate brachytherapy: comparisons with nomogram
      predictions in patients with non-metastatic prostate cancer presenting
      significant control of intra- and periprostatic disease.
AB  - Purpose: To assess the effectiveness of low-dose-rate (LDR) brachytherapy in
      patients with localized prostate cancer and to compare the outcome with
      predictions from Kattan and Partin nomograms at 60 months after seed
      implantation. Material and methods: One thousand, one hundred and eighty-seven
      patients with localized prostate cancer at low-, intermediate-, or high-risk of
      progression received LDR brachytherapy using iodine-125 seeds with curative
      intent, applied as monotherapy or in combination with external beam radiation
      therapy (EBRT), and/or androgen deprivation therapy (ADT). At 60 months after
      seed implantation, data of 1,064 patients (1,058 alive + 6 who died of prostate
      cancer) were analyzed for biochemical progression-free survival (bPFS) based on
      prostate-specific antigen (PSA) levels using the Phoenix definition. Five-year
      bPFS probabilities were determined for various risk group classifications
      (d'Amico, Mt. Sinai, MSKCC/Seattle, NCCN). Outcomes were also compared to patient
      individualized nomogram predictions of 5-year bPFS (Kattan 2002) and probability
      of organ-confined disease (Kattan 2002, Partin 2007). Results: Overall, 93.3%
      (993/1,064) of the patients were free of biochemical progression within 5 years,
      while the average 5-year bPFS probability according to the Kattan nomogram was
      significantly lower (85%, p < 0.001). Outcomes were significantly better than
      Kattan nomogram predictions in the subgroup of patients with monotherapy as well
      as in patients additionally treated with EBRT. Comparison of the overall outcome
      with nomogram predictions for organ-confined disease (Kattan nomogram: 50%;
      Partin nomogram: 65%) revealed a significant probability of LDR brachytherapy to
      destroy periprostatic tumor spread (p < 0.001) in all risk group constellations,
      even in high-risk patients. Conclusions: The results indicate high effectiveness
      of LDR brachytherapy in all risk groups, significantly better than predicted with
      the Kattan nomogram in most subgroups. The significant superiority of LDR
      brachytherapy compared to nomogram predictions of organ-confined disease suggests
      that LDR brachytherapy effectively controls both intra- and periprostatic
      disease.

PMID- 30237814
TI  - Development and preclinical testing of a novel biodegradable hydrogel vaginal
      packing technology for gynecologic high-dose-rate brachytherapy.
AB  - Purpose: We evaluated the performance of a novel hydrogel-based strategy
      developed for clinical use as vaginal packing using phantoms and cadavers, and to
      compare the hydrogel to gauze and balloon packing. Material and methods: The
      biocompatible hydrogel is based on a thiol-Michael addition reaction, with
      delivery of reagents into the vaginal cavity using a custom-made system. Soft
      cured cadavers were used for soft tissue-like mechanical properties. Two cadavers
      with intact uteri had magnetic resonance imaging (MRI) compatible with tandem and
      ovoids. For one cadaver, the temperature of the vaginal canal was measured before
      hydrogel application, during polymerization, and after hydrogel removal. The
      hydrogel packing and applicator was kept in a second cadaver, which was imaged
      using computed tomography (CT) and MRI. The hydrogel packing and imaging was
      repeated for an open multichannel MRI compatible, titanium-based vaginal cylinder
      placed in a post-hysterectomy cadaver. Results: The gel reaction occurred within
      90 seconds, indicating polymerization at clinical quantities with a 5 degrees C
      increase in vaginal temperature. CT and MRI imaging identified the hydrogel
      readily and showed a conformance to anatomy with few air pockets. The entire
      hydrogel packing was readily retrieved upon completion of imaging. Conclusions:
      The novel strategy for polyethylene glycol (PEG)-based hydrogel intra-vaginal
      packing was able to rapidly polymerize in human cadavers with minimal heat
      production. Delivery was efficient and able to fill the contours of the vaginal
      cavity and displace tissue away from the applicator axis. The hydrogel has
      favorable imaging characteristics on CT and MRI, and shows a potential for
      clinical use, warranting additional studies for the use in humans.

PMID- 30237815
TI  - EROS study: evaluation between high-dose-rate and low-dose-rate vaginal
      interventional radiotherapy (brachytherapy) in terms of overall survival and rate
      of stenosis.
AB  - Purpose: To compare the survival and toxicity outcomes in patients with
      endometrial cancer treated with either high-dose-rate (HDR) or low-dose-rate
      (LDR) vaginal brachytherapy (VBT) following external beam radiotherapy (EBRT).
      Material and methods: From January 2000 to December 2014, patients with
      endometrial cancer after radical hysterectomy with/without pelvic and/or para
      aortic lymphadenectomy were treated with adjuvant EBRT (45 Gy, 1.8 Gy/day to the
      whole pelvis) and subsequent VBT boost (HDR dose of 7 Gy in one fraction or LDR
      VBT dose of 25 Gy). The dose was prescribed at 0.5 cm from the surface of the
      applicator and the proximal half to two-thirds of the vagina was irradiated. The
      outcomes of patients were evaluated in terms of local control (LC), overall
      survival (OS), and rates of adverse events. Results: We analyzed data of 200
      patients treated with EBRT followed by HDR VBT boost in 78 patients and LDR VBT
      boost in 122 patients. With a median follow-up of 25 months (range, 6-163), 5
      year OS was 98% and 97% in the LDR and HDR groups, respectively (p = 0.37). The 5
      year LC was similar (93% in both groups) (p = 0.81). In multivariate analyses,
      none of the factors assessed (age, stage, grade) impacted OS (p = 0.37) or LC (p
      = 0.81). Patients treated with LDR VBT after EBRT had higher rates of acute
      gastrointestinal toxicity. No differences were found in acute genitourinary or
      hematological toxicities. Late toxicity such as vaginal stenosis was registered
      during regular follow-up visits and was similar in the two groups (p = 0.67).
      Conclusions: In our analysis, there were no differences in terms of OS and late
      toxicity outcomes for patients receiving LDR or HDR VBT. HDR VBT is a safe
      technique in comparison to LDR VBT.

PMID- 30237816
TI  - Clinical and dosimetric consequences of imperfect applicator insertion in
      cervical cancer brachytherapy.
AB  - Purpose: This study analyzes clinical consequences and dosimetric variations
      after imperfect brachytherapy insertions. It examines treatment decisions after
      such insertions in patients having difficult anatomy, which leads to good
      subsequent insertions with acceptable dose volume parameters. Material and
      methods: We reviewed images of all insertions performed during last one year and
      sorted faulty ones out. Clinical outcome was assessed, analyzing original
      treatment records. Repeat three-dimensional planning using identical dose
      optimization-technique compared their dosimetry. Statistical analysis using
      SPSS(r)-Statistics-software included Fisher's-exact-test to analyze predisposing
      factors for faulty insertions and predictive factors for subsequent satisfactory
      insertion. Friedman test was used to compare dose-volume-effects of
      normalization. Results: Eighteen of 292 brachytherapy plans revealed imperfect
      insertions, including thirteen perforations (4.5%). Lack of pre-planning,
      obstructing mass, narrow vagina, acute anteversion of uterus, and multi-parity
      were significant (p <= 0.05) predisposing factors for atypical insertions.
      Satisfactory optimization was possible after correcting acute anteflexion or
      positioning tandem in retroverted direction in uncorrectable retroverted uterus.
      Dose normalization at point A shifted optimized dose from contoured volume to
      point of normalization, often undesirably. This difference, however, was
      statistically not significant (p = 0.121). In patients having obstructing mass,
      subsequent insertions were perfect, and dose volume parameters were acceptable
      only when full prescribed dose was delivered to at least 60% volume of the mass
      after a faulty insertion (p < 0.001). Conclusions: Pre-planning by imaging is
      suggested in all cases of brachytherapy. Insertion of adequate length of tandem
      aligned to uterine axis is warranted for adequate tumor coverage. Whenever
      detected, acute anteflexion and mobile retroversion should be corrected. Tandem
      inserted in retroverted direction in uncorrectable retroverted uterus generates
      acceptable dose volume parameters. In cases with obstructive cervical mass, good
      subsequent insertion is possible with acceptable dose volume parameters, if
      planned dose can be delivered to its 60% volume.

PMID- 30237819
TI  - Comparison of clinical efficacy and complications of 125I seed brachytherapy and
      stereotactic body radiation therapy for recurrent pulmonary metastases from
      colorectal carcinoma.
AB  - Purpose: To evaluate the efficacies of 125I seed implantation and stereotactic
      body radiation therapy (SBRT) in treatment of recurrent lung metastases from
      colorectal cancer, to compare the tolerance of lung tissue to both forms of
      radiotherapy, and to analyze the factors that affect the prognosis. Material and
      methods: According to treatment received, thirty colorectal cancer patients with
      post-operative lung metastases were separated into two groups: 125I seed
      implantation group (group A; n = 16) and SBRT group (group B; n = 14). Patients
      were followed up, and local control rate, survival, and post-operative
      complications were analyzed retrospectively. Kaplan-Meier method was used for
      survival analysis. Cox proportional hazards model was used to identify the
      independent predictors of poor prognosis. Results: Survival was significantly
      different between group A and group B (median survival, 15 months and 11.5
      months, respectively; p = 0.015). Local control rates at the first, third, sixth,
      and twelfth months after treatment were all > 80%, with no significant difference
      between the two groups (p = 0.829). Significant differences were seen between the
      two groups in the number of treatments received (p = 0.009) and the incidence of
      radiation pneumonitis (p < 0.001) as well as radiation-induced pulmonary fibrosis
      (p = 0.005). On multivariate regression analysis radiation pneumonitis was an
      independent predictor of poor prognosis (HR = 3.356, 95% CI: 1.518-7.421; p =
      0.003). Conclusions: 125I seeds brachytherapy and SBRT are both effective for
      control of lung metastases but the former causes milder lung tissue damage. It
      can be repeated after short intervals, and appears to be a safe and efficient
      treatment for lung metastases.

PMID- 30237817
TI  - Radiobiological doses, tumor, and treatment features influence on local control,
      enucleation rates, and survival after epiescleral brachytherapy. A 20-year
      retrospective analysis from a single-institution: part I.
AB  - Purpose: To assess influence of the radiobiological doses, tumor, and treatment
      features on local control, enucleation rates, overall and disease-specific
      survival rates after brachytherapy for posterior uveal melanoma. Material and
      methods: Local control, enucleation, overall and disease-specific survival rates
      were evaluated on the base of 243 patients from 1996 through 2016, using plaques
      loaded with iodine sources. Clinical and radiotherapy data were extracted from a
      dedicated prospective database. Biologically effective dose (BED) was included in
      survival analysis using Kaplan-Meier and Cox regressions. The 3-, 5-, 10-, and 15
      year relative survival rates were estimated, and univariate/multivariate
      regression models were constructed for predictive factors of each item. Hazard
      ratio (HR) and confidence interval at 95% (CI) were determined. Results: The
      median follow-up was 73.9 months (range, 3-202 months). Cumulative probabilities
      of survival by Kaplan-Meier analysis at 3, 5, 10 and 15 years were respectively:
      96%, 94%, 93%, and 87%, for local control; 93%, 88%, 81%, and 73% for globe
      preservation; 98%, 93%, 84%, and 73% for overall survival, and 98%, 96%, 92%, and
      87% for disease-specific survival. By multivariate analysis, we concluded
      variables as significant: for local control failure - the longest basal diameter
      and the juxtapapillary location; for globe preservation failure - the longest
      basal dimension, the mushroom shape, the location in ciliary body, and the dose
      to the foveola; for disease-specific survival - the longest basal dimension. Some
      radiobiological doses were significant in univariate models but not in
      multivariate ones for the items studied. Conclusions: The results show as
      predictive factors of local control, enucleation, and disease-specific survival
      rates those related with the features of the tumor, specifically the longest
      basal dimension. There is no clear relation between radiobiological doses or
      treatment parameters in patients after brachytherapy.

PMID- 30237820
TI  - Effectiveness and safety of a robot-assisted 3D personalized template in 125I
      seed brachytherapy of thoracoabdominal tumors.
AB  - Purpose: This research aims to evaluate the effectiveness and safety of a robot
      assisted 3D personalized template in 125I seed brachytherapy of thoracoabdominal
      tumors. Material and methods: Forty-three patients with different tumors were
      involved in this research between 2013 and 2015. They were all eligible to 125I
      seed implantation based on robot-assisted 3D personalized template. Meanwhile, 51
      patients with similar tumors, which were treated with a conventional coplanar
      template, were involved for comparison. Follow-up was carried out after the
      surgery to evaluate the therapeutic efficacy, including overall survival (OS) of
      the patient and local control (LC) of the tumor. Complications were also
      summarized to evaluate the safety. Besides, statistical analysis was achieved to
      investigate possible factors associated with the result. Results: In the robot
      assisted 3D personalized template-guided brachytherapy, the median target volume
      treated by the prescription dose (V100) was 95.3% (range, 92.4-109.8), and the
      median dose administered to 90% of the target volume (D90) was 126.1 Gy (range,
      114.2-132.0), improved 5% and 8% compared with the conventional template-guided
      brachytherapy, respectively. The median OS was 30 months (95% CI: 19.4-40.6) and
      the rates of 2-year OS and LC were 58.1% and 86.0%, respectively. The median OS
      was prolonged 10 months and the 2-year OS and LC were improved 18.9% and 23.3%
      compared with the conventional template-guided brachytherapy, respectively.
      Conclusions: Through analysis of the selected patients with thoracoabdominal
      tumors, the robot-assisted 3D personalized template in 125I seed brachytherapy
      was a more effective and safer method. It can achieve a more favorable OS and LC.

PMID- 30237821
TI  - High-dose-rate brachytherapy in severe trismus: Making it happen!
AB  - Brachytherapy has been widely employed as a salvage or adjuvant modality in
      localized early and/or recurrent lesions. In recent years, advances in
      brachytherapy techniques have helped to achieve better loco-regional disease
      control and higher survival rates at the cost of limited morbidity. This is
      mainly owing to the development of technologically advanced three-dimensional
      computer planning systems and treatment delivery techniques. Low-dose-rate
      brachytherapy has been substituted by high-dose-rate and pulsed-dose-rate
      techniques, which allow better dose optimization. Inter-disciplinary approach
      results in fabrication of customized intra-oral surface mould, which allows
      accurate dose delivery, excellent dose distribution, and is less time-consuming.
      However, fabrication of surface mould becomes extremely challenging when intra
      oral anatomic factors are unfavorable. We present a report on the management of a
      previously-irradiated completely edentulous patient with severe trismus for whom
      high-dose-rate surface mould brachytherapy had been prescribed. A unique,
      reliable, and practical solution has been presented based firmly on the
      scientific knowledge of contemporary implant dentistry.

PMID- 30237822
TI  - Official Annual Meeting of Indian Brachytherapy Society8th ANNUAL CONFERENCE OF
      INDIAN BRACHYTHERAPY SOCIETY 2018 (IBSCON 2018) PROCEEDINGS.

PMID- 30237818
TI  - Radiobiological doses, tumor, and treatment features influence on outcomes after
      epiescleral brachytherapy. A 20-year retrospective analysis from a single
      institution: part II.
AB  - Purpose: To assess the influence of the radiobiological doses, tumor, and
      treatment features on retinopathy, cataracts, retinal detachment, optic
      neuropathy, vitreous hemorrhage, and neovascular glaucoma at the authors'
      institution after brachytherapy for posterior uveal melanoma. Material and
      methods: Medical records of 243 eyes with uveal melanoma, treated by iodine
      brachytherapy between 1996 and 2016 at a single center were analyzed. Clinical
      and radiotherapy data were extracted from a dedicated database. Biologically
      effective dose (BED) was included in survival analysis performed using Kaplan
      Meier and Cox regressions. Relative survival rates were estimated, and
      univariate/multivariate regression models were constructed for predictive factors
      of each item. Hazard ratio and confidence interval at 95% were determined.
      Variables statistically significant were analyzed and compared by log-rank tests.
      Results: The median follow-up was 73.9 months (range, 3-202 months). Cumulative
      probabilities of survival by Kaplan-Meier analysis at 3 and 5 years,
      respectively, were: 59% and 48% for retinopathy; 71% and 55% for cataracts; 63%
      and 57% for retinal detachment; 88% and 79% for optic neuropathy; 87% and 83% for
      vitreous hemorrhage; 92% and 89% for neovascular glaucoma, respectively. Using
      multivariate analysis, statistically significant risk factors were: age, tumor
      apical height, dose to foveola, and location of anterior border for retinopathy;
      age, dose to lens, type of plaque, and tumor shape, for cataracts; age, tumor
      apical height, and size of the plaque for retinal detachment; age, plaque shape,
      longest basal dimension, and BED to optic nerve for optic neuropathy; age, tumor
      apical height, and tumor shape for vitreous hemorrhage; tumor apical height and
      BED to foveola for neovascular glaucoma. Conclusions: Tumor factors in addition
      to radiation treatment may contribute to secondary effects. Enhanced clinical
      optimization should evaluate radiobiological doses delivered to the tumor volume
      and surrounding normal ocular structures.

PMID- 30237823
TI  - Preliminary study on chronic granulomatous disease in Sri Lanka.
AB  - Background: Chronic granulomatous disease (CGD) is a rare primary
      immunodeficiency of the phagocytic cells, which results in absent or diminished
      levels of microbicidal reactive oxygen species. The disease occurs due to
      germline mutations in the genes encoding the five subunits of NADPH oxidase
      complex. The present study is a pilot study to understand the clinical and
      genetic aspects of CGD in Sri Lanka. Methods: Clinical records of thirteen CGD
      patients were analysed and compared with similar studies performed in different
      countries and regions to identify patterns in demographics, clinical
      manifestations and infectious agents. Genomic DNA and cDNA were analysed in eight
      patients to identify mutations in CYBB and NCF1 genes, thereby to ascertain the
      potential X-linked and autosomal recessive (AR) CGD patients. Results: The onset
      of symptoms in the patient cohort was very early (mean 4.6 months) compared to 20
      months in India and 23.9 months in Latin America. Similarly, the age at diagnosis
      was lower (mean 1.6 years after birth) compared to other studies; 4.5 years in
      India and 6.1 years in Europe. Pulmonary manifestations were the most common
      (85%), followed by skin/subcutaneous infections (77%) and lymphadenopathy (62%).
      The death rate of local patients (38%) was higher than other countries (India
      35%, Europe 20%). Majority (77%) were treated for tuberculosis at some point in
      life. Genetic analysis confirmed six out of eight patients as X-linked CGD cases
      with mutations in CYBB gene. A novel splice site mutation was identified in P-07
      at position c.141+6 which resulted in the deletion of entire exon 2. Two siblings
      (P-05 and P-06) from consanguineous parents, were identified with AR-CGD based on
      the homozygous GT deletion mutation in NCF1 gene. Conclusions: The clinical
      presentation, manifestations and genetic subtypes in the local cohort, appear to
      be comparable with global trends. Mycobacterial infections should be investigated
      and treated with more prominence. Effective treatment options are required to
      control the high mortality rate.

PMID- 30237824
TI  - Impact of initial temporary abdominal closure in damage control surgery: a
      retrospective analysis.
AB  - Background: Damage control surgery has revolutionized trauma surgery. Use of
      damage control surgery allows for resuscitation and reversal of coagulopathy at
      the risk of loss of abdominal domain and intra-abdominal complications. Temporary
      abdominal closure is possible with multiple techniques, the choice of which may
      affect ability to achieve primary fascial closure and further complication.
      Methods: A retrospective analysis of all trauma patients requiring damage control
      laparotomy upon admission to an ACS-verified level one trauma center from 2011 to
      2016 was performed. Demographic and clinical data including ability and time to
      attain primary fascial closure, as well as complication rates, were recorded. The
      primary outcome measure was ability to achieve primary fascial closure during
      initial hospitalization. Results: Two hundred and thirty-nine patients met
      criteria for inclusion. Primary skin closure (57.7%), ABTheraTM VAC system (ABT)
      (15.1%), Bogota bag (BB) (25.1%), or a modified Barker's vacuum-packing (BVP)
      (2.1%) were used in the initial laparotomy. Patients receiving skin-only closure
      had significantly higher rates of primary fascial closure and lower hospital
      mortality, but also significantly lower mean lactate, base deficit, and
      requirement for massive transfusion. Between ABT or BB, use of ABT was associated
      with increased rates of fascial closure. Multivariate regression revealed primary
      skin closure to be significantly associated with primary fascial closure while BB
      was associated with failure to achieve fascial closure. Conclusions: Primary skin
      closure is a viable option in the initial management of the open abdomen,
      although these patients demonstrated less injury burden in our study. Use of
      vacuum-assisted dressings continues to be the preferred method for temporary
      abdominal closure in damage control surgery for trauma.

PMID- 30237825
TI  - Engineering xylose metabolism in thraustochytrid T18.
AB  - Background: Thraustochytrids are heterotrophic, oleaginous, marine protists with
      a significant potential for biofuel production. High-value co-products can off
      set production costs; however, the cost of raw materials, and in particular
      carbon, is a major challenge to developing an economical viable production
      process. The use of hemicellulosic carbon derived from agricultural waste, which
      is rich in xylose and glucose, has been proposed as a sustainable and low-cost
      approach. Thraustochytrid strain T18 is a commercialized environmental isolate
      that readily consumes glucose, attaining impressive biomass, and oil production
      levels. However, neither thraustochytrid growth capabilities in the presence of
      xylose nor a xylose metabolic pathway has been described. The aims of this study
      were to identify and characterize the xylose metabolism pathway of T18 and,
      through genetic engineering, develop a strain capable of growth on hemicellulosic
      sugars. Results: Characterization of T18 performance in glucose/xylose media
      revealed diauxic growth and copious extracellular xylitol production.
      Furthermore, T18 did not grow in media containing xylose as the only carbon
      source. We identified, cloned, and functionally characterized a xylose isomerase.
      Transcriptomics indicated that this xylose isomerase gene is upregulated when
      xylose is consumed by the cells. Over-expression of the native xylose isomerase
      in T18, creating strain XI 16, increased xylose consumption from 5.2 to 7.6 g/L
      and reduced extracellular xylitol from almost 100% to 68%. Xylose utilization
      efficiency of this strain was further enhanced by over-expressing a heterologous
      xylulose kinase to reduce extracellular xylitol to 20%. Moreover, the ability to
      grow in media containing xylose as a sole sugar was dependent on the copy number
      of both xylose isomerase and xylulose kinase present. In fed-batch fermentations,
      the best xylose metabolizing isolate, XI-XK 7, used 137 g of xylose versus 39 g
      by wild type and produced more biomass and fatty acid. Conclusions: The presence
      of a typically prokaryotic xylose isomerase and xylitol production through a
      typically eukaryotic xylose reductase pathway in T18 is the first report of an
      organism naturally encoding enzymes from two native xylose metabolic pathways.
      Our newly engineered strains pave the way for the growth of T18 on waste
      hemicellulosic feedstocks for biofuel production.

PMID- 30237826
TI  - Conditions promoting effective very high gravity sugarcane juice fermentation.
AB  - Background: Applying very high gravity (VHG) fermentation conditions to the
      sugarcane juice (SCJ) bioethanol industry would improve its environmental and
      economic sustainability without the need for major infrastructure changes or
      investments. It could enable a decrease in the consumption of biological and
      natural resources (cane/land, water and energy) while maintaining acceptable
      production parameters. The present study attempts to demonstrate and characterise
      an effective industrially relevant SCJ-VHG fermentation process. Results: An
      industry-like SCJ-VHG bioethanol production process with 30 and 35  degrees Bx
      broth was employed to investigate the effects of both the yeast strain used and
      nitrogen source supplementation on process yield, process productivity, biomass
      viability, glycerol concentration and retention-associated gene expression.
      Process performance was shown to be variably affected by the different process
      conditions investigated. Highest process efficiency, with a 17% (w/v) ethanol
      yield and only 0.2% (w/v) sugar remaining unfermented, was observed with the
      Saccharomyces cerevisiae industrial strain CAT-1 in 30  degrees Bx broth with
      urea supplementation. In addition, efficient retention of glycerol by the yeast
      strain was identified as a requisite for better fermentation and was consistent
      with a higher expression of glycerol permease STL1 and channel FPS1. Urea was
      shown to promote the deregulation of STL1 expression, overcoming glucose
      repression. The consistency between Fps1-mediated ethanol secretion and ethanol
      in the extracellular media reinforces previous suggestions that ethanol might
      exit the cell through the Fps1 channel. Conclusions: This work brings solid
      evidence in favour of the utilisation of VHG conditions in SCJ fermentations,
      bringing it a step closer to industrial application. SCJ concentrated up to 30 
      degrees Bx maintains industrially relevant ethanol production yield and
      productivity, provided the broth is supplemented with a suitable nitrogen source
      and an appropriate industrial bioethanol-producing yeast strain is used. In
      addition, the work contributes to a better understanding of the VHG-SCJ process
      and the variable effects of process parameters on process efficiency and yeast
      strain response.

PMID- 30237827
TI  - Sex-related differences in coordination and variability among foot joints during
      running.
AB  - Background: Women, as compared with men, have a higher proportion of injuries in
      the ankle/foot region. However, the reason for this sex-related difference in
      foot injuries remains unclear. Recently, joint coordination and variability of
      coordination have been suggested to be a critical index for defining both the
      state of injury and the potential risk of injury. The purpose of this study was
      to investigate sex-related differences in coordination and variability among the
      foot joints during running. Methods: Twelve healthy men and 12 healthy women ran
      on a treadmill. A modified vector coding technique was used to identify
      coordination and variability among foot joints involving the shank, rearfoot,
      midfoot, and forefoot segments, and categorized into the following four
      coordination patterns: in-phase with proximal dominancy, in-phase with distal
      dominancy, anti-phase with proximal dominancy, and anti-phase with distal
      dominancy. Results: There were no differences in all spatiotemporal parameters
      and in the foot strike angle between men and women. Coordination of variability
      of the foot joints during running was similar between men and women, but the anti
      phase with proximal dominancy in proportion of frontal rearfoot-shank vs. midfoot
      rearfoot couple (men; 7.2%, women; 13.9%) and midfoot-rearfoot vs. forefoot
      midfoot couple (men; 18.6%, women; 39.8%) in women was significantly increased
      compared to that in men. Other all coordination of the foot joints during running
      differed between men and women, and effect sizes of these parameters were all
      large. Conclusion: The results may be useful for understanding the underlying
      mechanism contributing to differences in injury risk in men and women, and may
      provide novel data on foot joint coordination and variability that could be used
      as reference data for both biomechanical and clinical running studies.

PMID- 30237828
TI  - Phylogenomic analysis reveals splicing as a mechanism of parallel evolution of
      non-canonical SVAs in hominine primates.
AB  - SVA (SINE-R-VNTR-Alu) elements are non-autonomous non-LTR (Long Terminal Repeat)
      retrotransposons. They are found in all hominoid primates but did not amplify to
      appreciable numbers in gibbons. Recently, phylogenetic networks of hominid
      (orangutan, gorilla, chimpanzee, human) SVA elements based on comparison of
      overall sequence identity have been reported. Here I present a detailed phylogeny
      of SVA_D elements in gorilla, chimpanzee and humans based on sorting of co
      segregating substitutions. Complementary comparative genomics analysis revealed
      that the majority (1763 out of 1826-97%) of SVA_D elements in gorilla represent
      species-specific insertions - indicating very low activity of the subfamily
      before the gorilla/chimpanzee-human split. The origin of the human-specific
      subfamily SVA_F could be traced back to a source element in the hominine common
      ancestor. The major expanding lineage-specific subfamilies were found to differ
      between chimpanzee and humans. Precursors of the dominant chimpanzee SVA_D
      subfamily are present in humans; however, they did not expand to appreciable
      levels. The analysis also uncovered that one of the chimpanzee-specific
      subfamilies was formed by splicing of the STK40 first exon to the SVA Alu-like
      region. Many of the 94 subfamily members contain additional 5' transductions -
      among them exons of 8 different other genes. Striking similarities to the MAST2
      containing human SVA_F1 suggest parallel evolution of non-canonical SVAs in
      chimpanzees and humans.

PMID- 30237830
TI  - FAQs (frequent asinine questions) on pharmacists' scope of practice.

PMID- 30237832
TI  - Cover: June 1942.

PMID- 30237833
TI  - Conspicuous by their absence: February 1940.

PMID- 30237829
TI  - Myeloid-derived suppressor cells in non-neoplastic inflamed organs.
AB  - Background: Myeloid-derived suppressor cells (MDSCs) are a highly heterogeneous
      population of immature myeloid cells with immunosuppressive function. Although
      their function in tumor-bearing conditions is well studied, less is known about
      the role of MDSCs in various organs under non-neoplastic inflammatory conditions.
      Main body: MDSCs are divided into two subpopulations, G-MDSCs and M-MDSCs, and
      their distribution varies between organs. MDSCs negatively control inflammation
      in inflamed organs such as the lungs, joints, liver, kidneys, intestines, central
      nervous system (CNS), and eyes by suppressing T cells and myeloid cells. MDSCs
      also regulate fibrosis in the lungs, liver, and kidneys and help repair CNS
      injuries. MDSCs in organs are plastic and can differentiate into osteoclasts and
      tolerogenic dendritic cells according to the microenvironment under non
      neoplastic inflammatory conditions. Conclusion: This article summarizes recent
      findings about MDSCs under inflammatory conditions, especially with respect to
      their function and differentiation in specific organs.

PMID- 30237831
TI  - Is it time for internal medicine pharmacists in primary care?

PMID- 30237835
TI  - The big three: August 1944.

PMID- 30237834
TI  - The pharmacist of tomorrow: February 1940.

PMID- 30237837
TI  - Exploring deprescribing opportunities for community pharmacists: Protocol for a
      qualitative study.

PMID- 30237838
TI  - The scoop on serotonin syndrome.

PMID- 30237836
TI  - Pharmacist prescribing and care improves cardiovascular risk, but what do
      patients think? A substudy of the RxEACH study.

PMID- 30237840
TI  - Patients' perceptions and use of natural health products.
AB  - Background: Despite a lack of good scientific evidence for their benefit,
      Canadians take a lot of natural health products (NHPs). The objectives of this
      study were to determine patients' perception of the efficacy, safety and quality
      of NHPs and to characterize NHP use. Methods: A standardized, 18-question survey
      was distributed to the general public through a variety of methods. Results: A
      total of 326 individuals completed the survey. Eighty-five percent of respondents
      take 1 or more NHPs. Forty-seven percent agreed/strongly agreed that NHPs are
      safer than prescription medications and 24% disagreed/strongly disagreed that
      prescription medications are more effective than NHPs. Three-quarters of
      respondents agreed/strongly agreed that health care providers should recommend
      NHPs more often, as most stated they preferred to take an NHP for both a minor
      ailment (82%) and chronic medical condition (60%). Respondents used 124 different
      NHPs, most commonly vitamin D, vitamin B and magnesium. Respondents purchased
      NHPs primarily from health/vitamin stores (66%) and accessed the Internet for
      information about them (64%). Younger, female respondents were more likely to
      take NHPs. Discussion: Patients appear to be comfortable foregoing education from
      health care professionals about the benefits and risks of NHPs. Patients' comfort
      with self-prescribing NHPs seems to stem from a perception of general efficacy
      and quality with little to no concern about harm and appears to be strongly
      influenced by lay sources of information. Conclusion: Most respondents take 1 or
      more NHPs, preferring to use NHPs over prescription medications for minor and
      chronic health concerns seemingly based on a perception of safety and quality.

PMID- 30237839
TI  - Recommendations for the safe use and handling of oral anticancer drugs in
      community pharmacy: A pan-Canadian consensus guideline.

PMID- 30237841
TI  - Pharmacists as immunizers, their pharmacies and immunization services: A survey
      of Ontario community pharmacists.
AB  - Background: To improve patient access to the influenza vaccine in Ontario,
      pharmacists have been authorized to administer the vaccine since 2012. A survey
      was conducted to describe pharmacist immunizers, their pharmacies and
      immunization services. Methods: Ontario community pharmacists completed an
      anonymous online survey regarding influenza immunization. Descriptive,
      comparative and multivariate statistics were used to analyze data on pharmacists'
      personal demographics, current workplace characteristics, immunization
      certification status and past and anticipated experience vaccinating. Results: Of
      the 4307 community pharmacists contacted, 18.4% (n = 780) completed the survey.
      Most (81.3%, n = 603) were certified to administer vaccines, with those
      practising in urban pharmacies twice as likely to be certified compared to
      pharmacists practising in rural pharmacies (odds ratio = 2.04; 95% confidence
      interval, 1.04 to 4.01, p = 0.04). In the past influenza season, 70% of
      pharmacists had administered over 50 vaccines and 37% worked at pharmacies that
      had administered more than 300 vaccines. Respondent-provided profiles of
      immunization services described partnerships with public health, a variety of
      approaches for in-pharmacy and external advertising and patient vaccine access
      mainly through walk-in. Discussion: Ontario community pharmacists demonstrate
      strong engagement with this expanded scope and there is further capacity for
      immunization service provision through engaging rural pharmacies, addition of
      other vaccines and leveraging the positive relationship with public health.
      Patients and the public benefit from easy access to the service and the
      additional in-store and external promotion of influenza vaccination that is
      provided by pharmacists and pharmacies. Conclusion: These provincial benchmarking
      data provide direction for maintaining and expanding community pharmacist
      provided influenza immunization.

PMID- 30237843
TI  - Cross-Canada updates.

PMID- 30237842
TI  - Issues spotlight: Medical cannabis.

PMID- 30237845
TI  - CALPA-IN NF1.

PMID- 30237844
TI  - Mental Health Among Latina Farmworkers and Other Employed Latinas in North
      Carolina.
AB  - The mental health of Latinas with manual occupations, particularly those employed
      in agriculture, is a public health concern. The goals of this analysis were to
      describe the mental health of Latina farmworkers, and to compare their mental
      health with that of other Latina manual workers. Participants included 35
      employed Latina farmworkers, 35 employed non-farmworkers, and 25 unemployed non
      farmworkers who completed interviews in 2012. Measures included stress, anxiety,
      depressive symptoms, elevated depressive symptoms, and risk for alcohol
      dependence. Farmworkers had greater stress and anxiety than did employed and
      unemployed non-farmworkers. Employed Latinas, whether farmworkers or in other
      occupations, had greater stress and anxiety than unemployed Latinas. Depressive
      symptoms, although high, did not differ significantly by occupation and
      employment. Few were at risk for alcohol dependence. Concrete steps are needed to
      address the mental health of Latina farmworkers, and to continue documentation of
      mental health concerns and their causes in this population.

PMID- 30237846
TI  - CpG island hypermethylation go circular (RNA).

PMID- 30237847
TI  - Checks and balances occur not only in government, but also in biology.

PMID- 30237848
TI  - MACROD2 deletions cause impaired PARP1 activity and chromosome instability in
      colorectal cancer.

PMID- 30237849
TI  - 177Lutetium-Dotatate delays decline in quality of life in patients with midgut
      neuroendocrine tumors.

PMID- 30237850
TI  - Prognostic markers for colorectal cancer.

PMID- 30237851
TI  - Population based germline testing for primary cancer prevention.

PMID- 30237852
TI  - mTORC1/2 inhibition re-sensitizes platinum-resistant ovarian cancer by disrupting
      selective translation of DNA damage and survival mRNAs.
AB  - Platinum resistance is a major cause of treatment failure and mortality in
      epithelial ovarian cancer. mTORC1/2 inhibitors, which impair mRNA translation,
      can re-sensitize resistant ovarian cancer cells to platinum chemotherapy but the
      mechanism remains poorly described. Using platinum-resistant OVCAR-3 cells
      treated with the selective mTORC1/2 inhibitor INK128/MLN128, we conducted genome
      wide transcription and translation studies and analyzed the effect on cell
      proliferation, AKT-mTOR signaling and cell survival, to determine whether
      carboplatin resistance involves selective mRNA translational reprogramming, and
      whether it is sensitive to mTORC1/2 inhibition. Gene ontology and Ingenuity
      Pathway Analysis (IPA) were used to categorize gene expression changes into
      experimentally authenticated biochemical and molecular networks. We show that
      carboplatin resistance involves increased mTORC1/2 signaling, resulting in
      selective translation of mRNAs involved in DNA damage and repair responses (DDR),
      cell cycle and anti-apoptosis (survival) pathways. Re-sensitization of ovarian
      cancer cell killing by carboplatin required only modest mTORC1/2 inhibition, with
      downregulation of protein synthesis by only 20-30%. Genome-wide transcriptomic
      and translatomic analyses in OVCAR-3 cells revealed that the modest
      downregulation of global protein synthesis by dual mTORC1/2 inhibition is
      associated with greater selective inhibition of DDR, cell cycle and survival mRNA
      translation, which was confirmed in platinum-resistant SKOV-3 cells. These data
      suggest a clinical path to re-sensitize platinum resistant ovarian cancer to
      platinum chemotherapy through partial inhibition of mTORC1/2, resulting in
      selective translation inhibition of DDR and anti-apoptosis protective mRNAs.

PMID- 30237853
TI  - Distinct urinary glycoprotein signatures in prostate cancer patients.
AB  - Novel biomarkers are needed to complement prostate specific antigen (PSA) in
      prostate cancer (PCa) diagnostic screening programs. Glycoproteins represent a
      hitherto largely untapped resource with a great potential as specific and
      sensitive tumor biomarkers due to their abundance in bodily fluids and their
      dynamic and cancer-associated glycosylation. However, quantitative
      glycoproteomics strategies to detect potential glycoprotein cancer markers from
      complex biospecimen are only just emerging. Here, we describe a glycoproteomics
      strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a
      view to investigate the diagnostic value of the glycoproteome to discriminate PCa
      from benign prostatic hyperplasia (BPH), two conditions that remain difficult to
      clinically stratify. Total protein extracts were obtained, concentrated and
      digested from urine of six PCa patients (Gleason score 7) and six BPH patients.
      The resulting peptide mixtures were TMT-labeled and mixed prior to a multi
      faceted sample processing including hydrophilic interaction liquid chromatography
      (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment
      and HILIC-HPLC pre-fractionation. The isolated N- and O-glycopeptides were
      detected and quantified using high resolution mass spectrometry. We accurately
      quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and
      observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across
      the two disease conditions. Importantly, a panel of 56 intact N-glycopeptides
      perfectly discriminated PCa and BPH (ROC: AUC = 1). This study has generated a
      panel of intact glycopeptides that has a potential for PCa detection.

PMID- 30237854
TI  - Investigation of novel chemotherapeutics for feline oral squamous cell carcinoma.
AB  - Feline oral squamous cell carcinomas (FOSCC) are highly aggressive neoplasms with
      short survival times despite multimodal treatment. FOSCC are similar to squamous
      cell carcinomas of the head and neck (SCCHN) in humans, which also present
      therapeutic challenges. The current study was undertaken to identify novel
      chemotherapeutics using FOSCC cell lines. A high throughput drug screen using
      1,952 drugs was performed to identify chemotherapeutics for further
      investigation. Two of the drugs identified in the drug screen, actinomycin D and
      methotrexate, and two drugs with similar molecular targets to drugs found to be
      efficacious in the screening, dinaciclib and flavopiridol, were selected for
      further investigation. Drug inhibition profiles were generated for each drug and
      cell line using an MTS assay. In addition, the effects of the drugs of interest
      on cell cycle progression were analyzed via a propidium iodide DNA labeling
      assay. Changes in caspase-3/7 activity after treatment with each drug were also
      determined. The findings demonstrated effectiveness of the drugs at nanomolar
      concentrations with sensitivity varying across cell lines. With all of the drugs
      except for actinomycin D, evidence for G1 arrest was found. Dinaciclib and
      flavopiridol were demonstrated to induce apoptosis. The results of the study
      suggest that the selected drugs are potential candidates for developing novel
      chemotherapeutic approaches to FOSCC. Through these studies, novel therapeutic
      strategies for the treatment of FOSCC can be developed to provide better care for
      affected cats which can also serve as proof of concept studies to inform
      translational studies in SCCHN in humans.

PMID- 30237855
TI  - The Jumonji-domain histone demethylase inhibitor JIB-04 deregulates oncogenic
      programs and increases DNA damage in Ewing Sarcoma, resulting in impaired cell
      proliferation and survival, and reduced tumor growth.
AB  - Ewing Sarcoma is an aggressive malignant neoplasm affecting children and young
      adults. Ewing Sarcoma is driven by transcription factor fusion oncoproteins, most
      commonly EWS/Fli1. While some patients can be cured with high-dose, multi-agent,
      chemotherapy, those that cannot currently have few options. Targeting of the
      driver oncofusion remains a logical therapeutic approach, but has proven
      difficult. Recent work has pointed to epigenetic mechanisms as key players, and
      potential new therapeutic targets, in Ewing Sarcoma. In this study we examined
      the activity of the pan-JHDM pharmacologic inhibitor JIB-04 in this disease. We
      show that JIB-04 potently inhibits the growth and viability of Ewing Sarcoma
      cells, and also impairs tumor xenograft growth. Effects on histone methylation at
      growth-inhibitory doses vary among cell lines, with most cell lines exhibiting
      increased total H3K27me3 levels, and some increased H3K4me3 and H3K9me3. JIB-04
      treatment widely alters expression of oncogenic and tumor suppressive pathways,
      including downregulation of known oncogenic members of the Homeobox B and D
      clusters. JIB-04 also disrupts the EWS/Fli1 expression signature, including
      downregulation of pro-proliferative pathways normally under positive oncofusion
      control. Interestingly, these changes are accompanied by increased levels of the
      EWS/Fli1 oncofusion, suggesting that the drug could be uncoupling EWS/Fli1 from
      its oncogenic program. All Ewing Sarcoma cell lines examined also manifest
      increased DNA damage upon JIB-04 treatment. Together, the findings suggest that
      JIB-04 acts via multiple mechanisms to compromise Ewing Sarcoma cell growth and
      viability.

PMID- 30237856
TI  - Fludarabine-resistance associates with ceramide metabolism and leukemia stem cell
      development in chronic lymphocytic leukemia.
AB  - Fludarabine (flu) -containing regimens such as flu, cyclophosphamide and
      rituximab have been established as one of the standard first line therapy in
      medically-fit chronic lymphocytic leukemia (CLL) patients. Therefore, flu
      refractory (primary flu-insensitivity or flu-caused relapse) remains a major
      problem causing treatment failure for CLL patients. We isolated the peripheral
      blood mononuclear cells (PBMCs) from CLL patients and treated with flu to find
      flu-refractory cases, and established flu-resistant clonal cells to study
      molecular mechanism of flu-resistance. By comparing parental MEC-2 cells, a human
      CLL cell line, we found that flu-resistant clonal cells were significantly
      increased lethal dose 50 of flu concentration, and up-regulated expression of P
      glycoprotein, a drug-resistant marker, glucosylceramide synthase (GCS), an enzyme
      that can convert ceramide to glucosylceramide, and CD34, a leukemia stem cell
      marker. Overexpression of GCS leads to promptly elimination of cellular ceramide
      levels and accumulation of glucosylceramide, which reduces apoptosis and promotes
      survival and proliferation of flu-resistant clonal cells. Furthermore, we
      demonstrated that the accumulation of glucosylceramide can be blocked by PDMP to
      restore flu-sensitivity in flu-resistant clonal cells. We also found that
      elevating glucosylceramide levels in flu-resistant clonal cells was associated
      with up-regulation of GCS and CD34 expression. Importantly, overexpression of GCS
      or CD34 was also determined in flu-refractory PBMCs. Our results show that flu
      resistance is associated with the alteration of ceramide metabolism and the
      development of leukemia stem cell-like cells. The flu-resistance can be reversed
      by GCS inhibition as a novel strategy for overcoming drug resistance.

PMID- 30237857
TI  - Trisenox disrupts MDM2-DAXX-HAUSP complex and activates p53, cell cycle
      regulation and apoptosis in acute leukemia cells.
AB  - Trisenox (TX) has been used in the treatment of both de novo and relapsed acute
      promyelocytic leukemia (APL) patients. Using in vitro APL cell lines model in
      this research, we report on a new target of TX action through disruption of MDM2
      DAXX-HAUSP complex, degradation of MDM2, and activation of p53 expression. TX
      induced stress signal was transmitted by protein kinase (ATM & ATR) and
      phosphorylation of its downstream targets CHK1, CHK2, ATM, and ATR, respectively
      at the Ser 345, Thr68, Ser1981 and Ser 428 residues involved in complex
      disruption and p53 up-regulation. TX-activated p53 led to cell cycle arrest and
      apoptosis in APL cells. Our results showed that TX inhibited cell proliferation,
      disrupted complex molecules expression and association in APL cells. Our
      functional studies indicated that TX-induced down-regulation of complex molecules
      expression was mostly neutralized in both p53 knockdown NB4 cells and nutilin-3
      treated KG1a cells. Hence our findings provide a functional evidence of TX action
      on cell cycle regulation and apoptosis in APL cells. This novel target of TX
      activity may be useful for designing new APL drugs.

PMID- 30237858
TI  - Comprehensive analysis identifying aberrant DNA methylation in rectal mucosa from
      ulcerative colitis patients with neoplasia.
AB  - Background: There are no biomarkers to facilitate the identification of patients
      with ulcerative colitis (UC) who are at high risk for developing colorectal
      cancer (CRC). In our current study, we used rectal tissues from UC patients to
      identify aberrant DNA methylations and evaluated whether they could be used to
      identify UC patients with coexisting colorectal neoplasia. Results: Using a
      training set, we identified 484 differentially methylated regions (DMRs) with
      absolute delta beta-values > 0.1 in rectal mucosa by using the ChAMP algorithm.
      Next, pathway enrichment analysis was performed using 484 DMRs to select
      coordinately methylated DMRs, resulting in the selection of 187 aberrant DMRs in
      rectal tissues from UC-CRC. Then, the Elastic Net classification algorithm was
      performed to narrow down optimal aberrant DMRs, and we finally selected 11 DMRs
      as biomarkers for identification of UC-CRC patients. The 11 chosen DMRs could
      discriminate UC patients with or without CRC in a training set (area under the
      curve, 0.96) and the validation set (area under the curve, 0.81). Conclusions: In
      conclusion, we identified 11 DMRs that could identify UC patients with CRC
      complications. Prospective studies should further confirm the validity of these
      biomarkers. Methods: We performed genome-wide DNA methylation profiles in rectal
      mucosal tissues (n = 48) from 24 UC-CRC and 24 UC patients in a training set.
      Next, we performed comprehensive DNA methylation analysis using rectal mucosal
      tissues (n = 16) from 8 UC-CRC and 8 UC patients for validation.

PMID- 30237859
TI  - Prediction of non-muscle-invasive bladder cancer recurrence by measurement of
      checkpoint HLAG's receptor ILT2 on peripheral CD8+ T cells.
AB  - Background and Objective: Recurrence of non-muscle invasive bladder cancer
      (NMIBC) after initial management occurs in 60-70% of patients. Predictive
      criteria for recurrence remain only clinical and pathological. The aim of this
      study was to investigate the prognostic significance of the proportion of
      checkpoint HLA-G's receptor ILT2-expressing peripheral CD8+ T cells. Results: The
      proportion of CD4+ILT2+and CD8+ILT2+ T cells was not increased in NMIBC compared
      to controls. However, a strong association was found between recurrence and
      CD8+ILT2+ T cell population levels (p = 0.0006). Two-year recurrence-free
      survival was 83% in patients with less than 18% CD8+ILT2+ T cells, 39% in the
      intermediary group, and 12% in patients with more than 46% CD8+ILT2+ T cells.
      Multivariate analyses demonstrated that the proportion of CD8+ILT2+ T cells was
      an independent predictive factor for recurrence. Adding CD8+ILT2+ T cells
      population level to clinical variables increased the predictive accuracy of the
      model by 4.5%. Materials and Methods: All patients treated for NMIBC between 2012
      and 2014 were included prospectively. Blood samples, tumor and clinico
      pathological characteristics were collected. HLA-G expression was measured using
      IHC, and CD8+ILT2+ T cell levels using flow cytometry. Association between HLA-G
      and CD8+ILT2+ T cell population levels with NMIBC risk of recurrence was
      investigated using Cox regression analyses. Prediction was measured using the
      concordance index statistic. Conclusions: We demonstrated a strong association
      between the proportion of circulating CD8+ILT2+ T cells and NMIBC risk of
      recurrence. Gain in prediction was substantial. If externally validated, such
      immunological marker could be integrated to predict NMIBC recurrence.

PMID- 30237860
TI  - Autotaxin-beta interaction with the cell surface via syndecan-4 impacts on cancer
      cell proliferation and metastasis.
AB  - Autotaxin (ATX) promotes cancer cell metastasis through the production of
      lysophosphatidic acid (LPA). ATX binds to alphavbeta3 integrins controlling
      metastasis of breast cancer cells. We screened a series of cancer cell lines
      derived from diverse human and mouse solid tumors for the capacity of binding to
      ATX and found only a modest correlation with their level of alphavbeta3 integrin
      expression. These results strongly suggested the existence of another cell
      surface ATX-interacting factor. Indeed, ATXalpha has been shown to bind heparan
      sulfate chains because of its unique polybasic insertion sequence, although the
      biological significance is unknown. We demonstrated here, that among all cell
      surface heparan-sulfate proteoglycans, syndecan-4 (SDC4) was essential for cancer
      cell interaction with ATXbeta but was restrained by heparan-sulfate chains. In
      addition, exogenous ATXbeta-induced MG63 osteosarcoma cell proliferation required
      physical interaction of ATXbeta with the cell surface via an SDC4-dependent
      mechanism. In a preclininal mouse model, targeting SDC4 on 4T1 mouse breast
      cancer cells inhibited early bone metastasis formation. Furthermore, SDC4
      prometastatic activity was totally abolished in absence of ATX expression. In
      conclusion our results determined that ATX and SDC4 are engaged in a reciprocal
      collaboration for cancer cell metastasis providing the rational for the
      development of novel anti-metastasis therapies.

PMID- 30237861
TI  - miR-665 targets c-MYC and HDAC8 to inhibit murine neuroblastoma cell growth.
AB  - Neuroblastoma is a common tumor of the peripheral nervous system in children.
      Highly aggressive MYC-driven neuroblastoma is defined by increased c-MYC and/or
      MYCN expression. This study employed a mouse neuroblastoma cell model to assess
      the role of miR-665 in tumorigenesis. We found that miR-665 suppresses mRNAs,
      targeting c-MYC and HDAC8, which are involved in neuroblastoma tumorigenesis.
      N6,2'-O-dibutyryladenosine 3':5'cyclic monophosphate (Bt2cAMP) inhibited
      neuroblastoma cell growth by inhibiting c-MYC and HDAC8 expression and activating
      caspase 3. Bt2cAMP also upregulated miR-665, and miR665 transfection mimicked the
      effects of Bt2cAMP, including reduced c-MYC and HDAC8 expression, increased
      caspase 3 activation, and reduced neuroblastoma cell growth. As compared to
      untreated cells, Bt2cAMP increased the number of cells in G1 phase by 50% and the
      number in G2-M phase by 5%, while the number of cells in S phase was reduced 2.8
      fold. Similarly, miR-665 transfection increased the number of cells in G1 phase
      by 16% and the number in G2M phase by 2%, and decreased the cells in S-phase by
      18%. These findings indicate miR-665 suppresses neuroblastoma tumorigenesis by
      inhibiting c-MYC and HDAC8 expression and suggest miR-665 has potential as an
      anti-neuroblastoma therapeutic.

PMID- 30237862
TI  - Biochemical and cellular consequences of the antithrombin p.Met1? mutation
      identified in a severe thrombophilic family.
AB  - Nature is always the best inspiration for basic research. A family with severe
      thrombosis and antithrombin deficiency, the strongest anticoagulant, carried a
      new mutation affecting the translation-start codon of SERPINC1, the gene encoding
      antithrombin. Expression of this variant in a eukaryotic cell system produced
      three different antithrombins. Two downstream methionines were used as
      alternative initiation codons, generating highly expressed small aglycosylated
      antithrombins with cytoplasmic localization. Wild-type antithrombin was generated
      by the use of the mutated AUU as initiation codon. Actually, any codon except for
      the three stop codons might be used to initiate translation in this strong Kozak
      context. We show unexpected consequences of natural mutations affecting
      translation-start codons. Downstream alternative initiation AUG codons may be
      used when the start codon is mutated, generating smaller molecules with potential
      different cell localization, biochemical features and unexplored consequences.
      Additionally, our data further support the use of other codons apart from AUG for
      initiation of translation in eukaryotes.

PMID- 30237863
TI  - Hematopoietic stem cell specific V-ATPase controls breast cancer progression and
      metastasis via cytotoxic T cells.
AB  - The interaction of recruited immune effector cells and cancer cells within tumor
      microenvironment (TME) shapes the fate of cancer progression and metastasis. Many
      cancers including breast cancer, express a specific vacuolar ATPase (a2V) on
      their cell surface which acidifies the extracellular milieu helping cancer cell
      proliferation and metastasis. To understand the role of immune cell-associated
      a2V during breast tumor pathogenesis, we knocked-out a2V (KO) from the
      hematopoietic stem cells (HSC) and generated breast tumors in mice. The a2V-KO
      mice developed faster growing, larger, and metastatic breast tumors compared to
      control mice. Further investigation of the TME revealed a significant reduction
      in the presence of CD4+ and CD8+ T cells in the a2V-KO tumors. Targeted RNA-Seq
      of the cells of the TME demonstrated that pro-inflammatory cytokines, death
      receptors, death receptor ligands, and cytotoxic effectors were significantly
      down-regulated within the a2V-KO TME. Interestingly, analysis of immune cells in
      the blood, spleen, and thymus of the non-tumor bearing a2V-KO mice revealed a
      significant decrease in CD4+ and CD8+ T cell populations. For the first time,
      this study demonstrates that inhibition of V-ATPase expression in HSC leads to a
      decrease in CD4+ and CD8+ T cell populations and thus promotes breast tumor
      growth and metastasis.

PMID- 30237865
TI  - Correction: Antibody targeting TSPAN12/beta-catenin signaling in
      vasoproliferative retinopathy.
AB  - [This corrects the article DOI: 10.18632/oncotarget.23401.].

PMID- 30237864
TI  - Prevalence of MDM2 amplification and coalterations in 523 advanced cancer
      patients in the MD Anderson phase 1 clinic.
AB  - Background: TP53 is the most commonly mutated gene in cancer and codes for the
      best studied tumor suppressor, p53. MDM2 is involved in the negative regulation
      of p53 and itself serves as an oncogene, reported to be overexpressed in several
      cancer tumor types. In this retrospective study, we assessed the occurrence of
      MDM2 amplification among patients with various types of cancers and its
      association with clinical factors, other genetic aberrations, and response to
      targeted therapy in a phase I clinical trial setting. Methods: Samples from
      patients with advanced solid tumors who had been referred to the MD Anderson
      phase I clinical trials program between January 2011 and January 2016 were
      collected and analyzed for MDM2 amplification using FoundationOne's genomic
      profiling assay. Patients whose tumors expressed MDM2 amplification were compared
      to those with tumors of the same histologic types without MDM2 amplification.
      Results: We tested tumors from 523 patients, of which 23 (4.4%) had MDM2
      amplification. The highest prevalence of MDM2 amplification was in sarcoma (57%),
      breast cancer (13%) and bladder cancer (9%). Six patients with liposarcoma were
      treated on phase I protocol with an MDM2 inhibitor. The most common molecular
      aberrations co-occurring with MDM2 amplification was CDK4 amplification (70%).
      TP53 mutation was also detected in 7 patients (30%). Conclusion: MDM2
      amplification was most commonly associated with liposarcoma. Concomitant
      alterations in additional genes such as CDK4 amplification and TP53 mutations,
      along with variable responses to targeted therapies including MDM2 inhibitors,
      suggest that further combinational studies are needed to target this population.

PMID- 30237868
TI  - The balance of two opposing factors Mad and Myc regulates cell fate during tissue
      remodeling.
AB  - Cell proliferation and differentiation are two distinct yet coupled processes in
      development in diverse organisms. Understanding the molecular mechanisms that
      regulate this process is a central theme in developmental biology. The intestinal
      epithelium is a highly complex tissue that relies on the coordination of cell
      proliferation within the crypts and apoptosis mainly at the tip of the villi,
      preservation of epithelial function through differentiation, and homeostatic cell
      migration along the crypt-villus axis. Small populations of adult stem cells are
      responsible for the self-renewal of the epithelium throughout life. Surprisingly,
      much less is known about the mechanisms governing the remodeling of the intestine
      from the embryonic to adult form. Furthermore, it remains unknown how thyroid
      hormone (T3) affects stem cell development during this postembryonic process,
      which is around birth in mammals when T3 level increase rapidly in the plasma.
      Tissue remodeling during amphibian metamorphosis is very similar to the
      maturation of the mammalian organs around birth in mammals and is regulated by
      T3. In particular, many unique features of Xenopus intestinal remodeling during
      metamorphosis has enabled us and others to elucidate how adult stem cells are
      formed during postembryonic development in vertebrates. In this review, we will
      focus on recent findings on the role of Mad1/c-Myc in cell death and
      proliferation during intestinal metamorphosis and discuss how a Mad1-c-Myc
      balance controls intestinal epithelial cell fate during this T3-dependent
      process.

PMID- 30237867
TI  - Clustering the autisms using glutamate synapse protein interaction networks from
      cortical and hippocampal tissue of seven mouse models.
AB  - Background: Autism spectrum disorders (ASDs) are a heterogeneous group of
      behaviorally defined disorders and are associated with hundreds of rare genetic
      mutations and several environmental risk factors. Mouse models of specific risk
      factors have been successful in identifying molecular mechanisms associated with
      a given factor. However, comparisons among different models to elucidate
      underlying common pathways or to define clusters of biologically relevant disease
      subtypes have been complicated by different methodological approaches or
      different brain regions examined by the labs that developed each model. Here, we
      use a novel proteomic technique, quantitative multiplex co-immunoprecipitation or
      QMI, to make a series of identical measurements of a synaptic protein interaction
      network in seven different animal models. We aim to identify molecular
      disruptions that are common to multiple models. Methods: QMI was performed on 92
      hippocampal and cortical samples taken from seven mouse models of ASD: Shank3B,
      Shank3Deltaex4-9, Ube3a2xTG, TSC2, FMR1, and CNTNAP2 mutants, as well as E12.5
      VPA (maternal valproic acid injection on day 12.5 post-conception). The QMI panel
      targeted a network of 16 interacting, ASD-linked, synaptic proteins, probing 240
      potential co-associations. A custom non-parametric statistical test was used to
      call significant differences between ASD models and littermate controls, and
      Hierarchical Clustering by Principal Components was used to cluster the models
      using mean log2 fold change values. Results: Each model displayed a unique set of
      disrupted interactions, but some interactions were disrupted in multiple models.
      These tended to be interactions that are known to change with synaptic activity.
      Clustering revealed potential relationships among models and suggested deficits
      in AKT signaling in Ube3a2xTG mice, which were confirmed by phospho-western
      blots. Conclusions: These data highlight the great heterogeneity among models,
      but suggest that high-dimensional measures of a synaptic protein network may
      allow differentiation of subtypes of ASD with shared molecular pathology.

PMID- 30228858
TI  - Association of adverse childhood experiences with functional identity and
      impulsivity among adults: a cross-sectional study.
AB  - Introduction: The present study explores the association of adverse childhood
      experiences with impulsivity and functional identity among Pakistani adults.
      Methods: In this cross-sectional study, 260 Pakistani medical students aged 18
      and above were approached. A consent form, a questionnaire on sociodemographic
      characteristics, and an English versions of the Adverse Childhood Experiences
      (ACE) scale, Functions of Identity scale (FIS) and Barratt's Impulsiveness Scale
      (BIS-11) was employed in this study. All data were analyzed in SPSS v. 20.
      Results: A total of 122 (52.6%) of respondents had experienced at least one
      adverse childhood experience. Verbal, physical, sexual adverse events and poor
      support and affection from family were the most reported adverse events. ACE
      scores yielded a significantly positive association with cognitive stability,
      perseverance and motor impulsivity on the Barrat's impulsivity scale. Whereas, it
      yielded negative association with structure and harmony subscales of the
      functional identity as well as cognitive complexity subscale of the impulsivity
      scale. Conclusions: A high proportion of Pakistani medical students reported
      adverse childhood experiences, which lead to impulsive behaviors and poor
      functional identities.

PMID- 30237866
TI  - Clinical Mass Spectrometry in the Bioinformatics Era: A Hitchhiker's Guide.
AB  - Mass spectrometry (MS) is a sensitive, specific and versatile analytical
      technique in the clinical laboratory that has recently undergone rapid
      development. From initial use in metabolic profiling, it has matured into
      applications including clinical toxicology assays, target hormone and metabolite
      quantitation, and more recently, rapid microbial identification and antimicrobial
      resistance detection by matrix assisted laser desorption ionization-time of
      flight mass spectrometry (MALDI-TOF MS). In this mini-review, we first succinctly
      outline the basics of clinical mass spectrometry. Examples of hard ionization
      (electron ionization) and soft ionization (electrospray ionization, MALDI) are
      presented to demonstrate their clinical applications. Next, a conceptual
      discourse on mass selection and determination is presented: quadrupole mass
      filter, time-of-flight mass spectrometer and the Orbitrap; and MS/MS (tandem-in
      space, tandem-in-time and data acquisition), illustrated with clinical examples.
      Current applications in (1) bacterial and fungal identification, antimicrobial
      susceptibility testing and phylogenetic classification, (2) general unknown urine
      toxicology screening and expanded new-born metabolic screening and (3) clinical
      metabolic profiling by gas chromatography are outlined. Finally, major
      limitations of MS-based techniques, including the technical challenges of matrix
      effect and isobaric interference; and novel challenges in the post-genomic era,
      such as protein molecular variants, are critically discussed from the perspective
      of service laboratories. Computer technology and structural biology have played
      important roles in the maturation of this field. MS-based techniques have the
      potential to replace current analytical techniques, and existing expertise and
      instrument will undergo rapid evolution. Significant automation and adaptation to
      regulatory requirements are underway. Mass spectrometry is unleashing its
      potentials in clinical laboratories.

PMID- 30237869
TI  - POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of
      Innovation and Technology Health (EIT Health) project.
AB  - Allergic rhinitis (AR) is impacted by allergens and air pollution but
      interactions between air pollution, sleep and allergic diseases are
      insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and
      Rhinitis) is a project of the European Institute of Innovation and Technology
      (EIT Health). It will use a freely-existing application for AR monitoring that
      has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000
      users, TLR8). The Allergy Diary will be combined with a new tool allowing queries
      on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as
      existing longitudinal and geolocalized pollution data. Machine learning will be
      used to assess the relationship between air pollution, sleep and AR comparing
      polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be
      confirmed in 2019 and extended by the individual prospective assessment of
      pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a
      demonstrator of sleep disorder that can be modulated in terms of symptoms and
      severity by air pollution and AR. The geographic information system GIS will map
      the results. Consequences on quality of life (EQ-5D), asthma, school, work and
      sleep will be monitored and disseminated towards the population. The impacts of
      POLLAR will be (1) to propose novel care pathways integrating pollution, sleep
      and patients' literacy, (2) to study sleep consequences of pollution and its
      impact on frequent chronic diseases, (3) to improve work productivity, (4) to
      propose the basis for a sentinel network at the EU level for pollution and
      allergy, (5) to assess the societal implications of the interaction. MASK paper N
      degrees 32.

PMID- 30237870
TI  - Assessment of variability in traction interventions for patients with low back
      pain: a systematic review.
AB  - Background: Previous systematic reviews have concluded that lumbar traction is
      not effective for patients with low back pain (LBP), yet many clinicians continue
      to assert its clinical effectiveness. Objective: To systematically identify
      randomized controlled trials (RCTs) of traction and explore the variability of
      traction interventions used in each RCT. Method: A literature search started in
      September 2016 to retrieve systematic reviews and individual RCTs of lumbar
      traction. The term "lumbar traction" and other key words were used in the
      following databases: Cochrane Registry, MEDLINE, EMBASE, and CINAHL. The
      retrieved systematic reviews were used to extract individual RCTs. The most
      current systematic review included RCTs from inception until August 2012. We
      performed an additional literature search to update this systematic review with
      newer RCTs published between September 2012 and December 2016. All of the
      identified RCTs were combined and summarized into a single evidence table.
      Results: We identified a total of 37 traction RCTs that varied greatly in their
      method of traction intervention. The RCTs included several types of traction:
      mechanical (57%), auto-traction (16%), manual (10.8%), gravitational (8.1%) and
      aquatic (5.4%). There was also great variability in the types of traction force,
      rhythm, session duration and treatment frequency used in the RCTs. Patient
      characteristics were a mixture of acute, subacute and chronic LBP; with or
      without sciatica. Conclusion: There is wide variability in the type of traction,
      traction parameters and patient characteristics found among the RCTs of lumbar
      traction. The variability may call into question the conclusion that lumbar
      traction has little no or value on clinical outcomes. Also, this variability
      emphasizes the need for targeted delivery methods of traction that match
      appropriate dosages with specific subgroups of patients with LBP.

PMID- 30228875
TI  - Haematology of N'Dama and West African Shorthorn cattle herds under natural
      Trypanosoma vivax challenge in Ghana.
AB  - Background: Animal trypanosomosis is a major cause of economic loss in livestock
      production in Africa. A suggested control measure is to use breeds with traits of
      trypanotolerance. The study examines the effect of natural Trypanosoma vivax
      challenge on haematological parameters in two trypanotolerant cattle [N'Dama and
      West African Shorthorn (WASH)] herds. Methods:Trypanosoma vivax-specific primers
      were used to diagnose T. vivax infection in an N'Dama herd at Cape Coast in
      southern Ghana and a WASH herd at Chegbani in northern Ghana from May to July
      2011 in a cross-sectional study. Levels of haematological parameters comprising
      packed cell volume (PCV), haemoglobin (Hb) concentration and red blood cell (RBC)
      and total white blood cell (TWBC) counts; differential WBC counts (neutrophils,
      lymphocytes, eosinophils, monocytes and basophils); and RBC indices of mean
      corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular
      haemoglobin concentration (MCHC) were determined in blood samples and then
      compared between infected and uninfected cattle. Results: We found that
      haematological indices for infected and uninfected animals in both breeds were
      within the normal range. However, the mean PCV values for T. vivax-infected WASH
      and N'Dama were lower in infected compared to uninfected animals. The difference
      was significant ( p< 0.05) in N'Dama but not in WASH. Conclusion: Despite the
      presence of infection by T. vivax, N'Dama and WASH cattle maintained their
      haematological parameters within acceptable normal ranges,  which confirms their
      trypanotolerant trait. This highlights the need for low-input traditional African
      farmers in medium, high and severe tsetse challenge areas to be educated on the
      advantages of N'Dama and WASH breeds to increase their utilization in integrated
      tsetse and trypanosomosis control programmes.

PMID- 30228876
TI  - Predictive physiological anticipatory activity preceding seemingly unpredictable
      stimuli: An update of Mossbridge et al's meta-analysis.
AB  - Background: This is an update of the Mossbridge et al's meta-analysis related to
      the physiological anticipation preceding seemingly unpredictable stimuli which
      overall effect size was 0.21; 95% Confidence Intervals: 0.13 - 0.29 Methods:
      Nineteen new peer and non-peer reviewed studies completed from January 2008 to
      June 2018 were retrieved describing a total of 27 experiments and 36 associated
      effect sizes. Results: The overall weighted effect size, estimated with a
      frequentist multilevel random model, was: 0.28; 95% Confidence Intervals: 0.18
      0.38; the overall weighted effect size, estimated with a multilevel Bayesian
      model, was: 0.28; 95% Credible Intervals: 0.18-0.38. The weighted mean estimate
      of the effect size of peer reviewed studies was higher than that of non-peer
      reviewed studies, but with overlapped confidence intervals: Peer reviewed: 0.36;
      95% Confidence Intervals: 0.26-0.47; Non-Peer reviewed: 0.22; 95% Confidence
      Intervals: 0.05-0.39. Similarly, the weighted mean estimate of the effect size of
      Preregistered studies was higher than that of Non-Preregistered studies:
      Preregistered: 0.31; 95% Confidence Intervals: 0.18-0.45; No-Preregistered: 0.24;
      95% Confidence Intervals: 0.08-0.41. The statistical estimation of the
      publication bias by using the Copas selection model suggest that the main
      findings are not contaminated by publication bias. Conclusions: In summary, with
      this update, the main findings reported in Mossbridge et al's meta-analysis, are
      confirmed.

PMID- 30228877
TI  - Analysis of the complete genome of hepatitis B virus subgenotype C2 isolate
      NHB17965 from a patient with uncomplicated chronicity.
AB  - The burden of chronic hepatitis B virus (HBV) infections is increasingly detected
      nowadays. Herein, we report a complete genome of HBV subgenotype C2 (HBV/C2) from
      a patient with chronic HBV infection. Complete genome analysis revealed that the
      isolated strain was a non-recombinant wild type and had several regular
      substitutions in the reverse transcriptase domain and small surface proteins of
      HBV. This study may help clinicians and scientists gain in-depth knowledge on the
      current substitutions of HBV/C2 genome and to identify potential therapies
      against chronic HBV infections.

PMID- 30237875
TI  - Fifty years of primary health care in the rainforest: temporal trends in
      morbidity and mortality in indigenous Amerindian populations of Suriname.
AB  - Background: The Amazonian Amerindian populations living in the southern and
      southwestern hinterlands of Suriname (South America) have come into contact with
      western health care since approximately fifty years ago. In this study, secondary
      data were used to assess the impact of Medical Mission's fifty-year old primary
      health care program on the health status of these populations. Methods: Using
      data from the primary health care facilities of Medical Mission for 1965-1970,
      1973-1977, 1982-1985, and 1997-2014, temporal trends in incidence and mortality
      of respiratory tract infections, gastroenteritis, and malaria; population
      composition; birth and death rates; and polyclinic consultations in these
      communities have been assessed over the period between 1965 and 2014. Results: In
      the period covered by this study, the incidence of respiratory tract infections
      and gastroenteritis declined by about 75% and 53%, respectively, while malaria
      incidence rose sharply from the 1980s through 2005 but subsequently declined to
      levels approximating elimination. Crude death rates dropped by about 70% while
      birth rates declined by about 50% in the 1980s and since then remained at this
      level. The population doubled in size and increased in all age groups,
      particularly in the age group of >=59 years. The infant mortality rate declined
      by 50%. In addition, the average yearly number of polyclinic visits per person
      decreased 6- to 7-fold during this period. Conclusions: The significant reduction
      of the infectious disease burden; the doubling of the population size and the
      growth of the proportion of elderly individuals due to the declining death rates;
      the declining infant mortality rates to levels comparable to the national average
      as well as the decline in average numbers of polyclinic consultations per person,
      indicate that Medical Missions health service provision achieved its goal of
      improving the health and survival of the indigenous people by providing free,
      accessible and permanent medical services. Building upon this successful
      experience Medical Mission could be instrumental in addressing potential
      contemporary life-style related health threats.

PMID- 30237876
TI  - Factors influencing the allocation of China's development assistance for health.
AB  - Background: China has been described as a "rogue" donor suspected of using
      foreign assistance to obtain raw materials, promote exports, and strengthen its
      business links with aid recipient countries. However, the factors influencing
      China's development assistance policy have rarely been analysed, particularly
      those related to its health aid. This study explores the factors that could
      affect the allocation of China's development assistance for health (DAH) from
      three key aspects: recipient need, recipient merit, and donor interest. Methods:
      Analysis was based on cross-sectional data of China's DAH from 2006 to 2014. This
      study explores the following characteristics of the 82 recipient countries
      identified in the data: the association between China's allocation of DAH and
      recipient need (measured by Gross Domestics Product [GDP] per capita and all
      cause Disability-Adjusted Life Years [DALYs]), recipient merit (measured by
      government effectiveness and human rights violations) and donor interests
      (measured by China's export, United Nations voting alignment, and recipient
      natural resources). A stratified analysis was conducted to understand these
      associations in different development contexts and the factors that influenced
      each type of DAH. Results: Multivariate Spearman correlation suggested that the
      most significant factors influencing China's allocation of DAH were the recipient
      countries' GDP per capita (r = -0.31941, P = 0.0049) and human rights conditions
      (r = -0.23227, P = 0.0435). Health workforce was associated with medical team
      deployment (r = -0.20929, P = 0.0715), while malaria DALYs was associated with
      anti-malaria center establishment (r = 0.46473, P < 0.0001). According to the sub
      group analysis, donor interests such as trade and natural resources only slightly
      influenced DAH allocation. Conclusion: Recipient need and merit strongly
      influence China's DAH allocation while donor interests only slightly influence
      DAH allocation in certain development contexts.

PMID- 30237877
TI  - The resilience of integrated community case management in acute emergency: a case
      study from Unity State, South Sudan.
AB  - Background: An active conflict in South Sudan in late 2013/early 2014 displaced
      approximately 2 million people over the course of several months. In May 2015,
      the International Rescue Committee and UNICEF conducted a mixed-methods case
      study of the impact of that acute emergency on integrated community case
      management (iCCM) of childhood illness programming in Payinjiar County, Unity
      State. The objective was to document the operations of an iCCM program during an
      acute crisis and to assess the program's ability to continue operations. Results:
      This mixed-methods case study is comprised of semi-structured interviews and
      focus groups with key stakeholders such as policymakers, program implementers,
      community health workers (CHWs), and caregivers on their experience with iCCM
      programming during this time period. Routine program data were also analyzed to
      assess the effect of the crisis on key health indicators. Findings: Internally
      displaced persons (IDPs) nearly doubled the population in Payinjiar. Some
      displaced CHWs continued to provide treatment in host communities when they were
      able to take supplies with them. Despite no formal community mobilization effort
      by the iCCM program, many IDPs identified CHWs in the communities they were
      displaced to and obtained care from them. Caregivers who had been internally
      displaced reported preferring care from CHWs especially in contrast to risking an
      insecure journey to health facilities. The total number of treatments provided
      per month by CHWs dropped during the acute crisis, but recovered to pre-crisis
      levels within six months. CHW supervisors attempted to continue supervision by
      utilizing their networks to track down displaced CHWs and assess the security
      situation prior to visits. The monthly supervision rate dropped to the lowest
      level of 77% in February 2014, but rebounded to 91% by August 2014. Several CHWs
      and community leaders qualitatively validated this claim of sustained
      supervision. Conclusions: CHWs, including those who were internally displaced,
      continued to provide treatment for childhood illnesses during an acute emergency,
      and service provision recovered faster to pre-crisis levels than the formal
      health sector. International donors and humanitarian actors should recognize iCCM
      as a potentially high-impact humanitarian response. Flexible funding from donors
      would enable further evidence generation on iCCM approaches and improvements that
      could both sustain and enhance programming in acute crisis.

PMID- 30237879
TI  - Case report of Wolfe grafting for the management of bilateral cicatricial eyelid
      ectropion following severe burn injuries.
AB  - Introduction: Eye lid reconstruction followed by severe, extensive body and
      facial burns represents a surgical challenge due to difficulties to obtain
      proper, healthy skin graft, tissue ischemia and necrosis. Presentation of case:
      We present a reconstructive lid surgery of cicatricial bilateral lower eyelid
      ectropion in a case of 31-year-old man who sustained thermal injuries, affecting
      more than 60% of total body surface area, causing severe, deep dermal burns.
      Reconstruction was made using the technique of skin cantus-to-cantus incision,
      contracture release, orbicularis liberation and lid elevation; and oversizing
      free full-thickness skin graft (FTSG) (Wolfe technique) from the left inguinal
      region, as the only healthy skin on the entire body surface. Residual lower left
      lid laxity was addressed by pentagonal wedge resection, not interrupting marginal
      arcade vessels, thus minimizing ischemia. Discussion: Method of choice of the
      graft type has been much debated question; however, significantly less
      reoccurrence rate of ectropion was observed using FTSG. Time of grafting should
      be balanced to avoid excess granulation and, thus scaring caused by delayed
      grafting time, or poor graft adherence caused by premature grafting. An
      interruption of the marginal arcade vessels should not be performed due to
      already severe ischemic process and increased risk for lid necrosis. Conclusion:
      Major issues when addressing cicatricial ectropion followed by severe burns are:
      right donor site selection, appropriate graft thickness with the least possible
      disturbance of the affected place vascularisation, followed by immediate grafting
      after debridement of scaring and unhealthy tissue, with generous preservation of
      the orbicularis muscle.

PMID- 30237878
TI  - Bis(9)-(-)-Meptazinol, a novel dual-binding AChE inhibitor, rescues cognitive
      deficits and pathological changes in APP/PS1 transgenic mice.
AB  - Background: Alzheimer's disease (AD) is a progressive and irreversible
      neurodegenerative brain disorder, which is the most common form of dementia.
      Intensive efforts have been made to find effective and safe treatment against AD.
      Acetylcholinesterase inhibitors (AChEIs) have been widely used for the treatment
      of mild to moderate AD. In this study, we investigated the effect of Bis(9)-(-)
      Meptazinol (B9M), a novel potential dual-binding acetylcholinesterase (AChE)
      inhibitor, on learning and memory abilities, as well as the underlying mechanism
      in the APP/PS1 mouse model of AD. Methods: B9M (0.1 MUg/kg, 0.3 MUg/kg, and 1
      MUg/kg) was administered by subcutaneous injection into eight-month-old APP/PS1
      transgenic mice for four weeks. Morris water maze, nest-building and novel object
      recognition were used to examine learning and memory ability. Abeta levels and
      Abeta plaque were evaluated by ELISA and immunochemistry. Results: Our results
      showed that chronic treatment with B9M significantly improved the cognitive
      function of APP/PS1 transgenic mice in the Morris water maze test, nest-building
      test and novel object recognition test. Moreover, B9M improved cognitive deficits
      in APP/PS1 mice by a mechanism that may be associated with its inhibition of the
      AChE activity, Abeta plaque burden, levels of Abeta and the consequent activation
      of astrocytes and microglia in the brain of APP/PS1 transgenic mice. Most of
      important, the most effective dose of B9M in the present study is 1 MUg/kg, which
      is one thousand of the dosage of Donepezil acted as the control treatment.
      Furthermore, B9M reduced Abeta plaque burden better than Donepezil. Conclusion:
      These results indicate that B9M appears to have potential as an effective AChE
      inhibitor for the treatment of AD with symptom-relieving and disease-modifying
      properties.

PMID- 30237880
TI  - Severe hepatic abscess: Conservative treatment of multi-organ infection by
      Stenotrophomonas maltophilia. A case report.
AB  - Introduction: Stenotrophomonas Malthophilia (SM) is generally considered a
      nosocomial pathogen but it has also been reported as a cause of community
      acquired systemic infection. We reported a rare case of SM multi-organ infection
      involving the liver and the left ocular region. Presentation of the case: A 64
      years old man presented with fever for 4 days and acute blindness of the left
      eye. We performed an abdomen and head CT scan that identified respectively a
      liver lesion in central region, likely a hepatic abscess, and inflammation
      process involving the left eye. After 5 days of antibiotic therapy, no
      improvement of the clinical condition was noted. A CT guided drainage of the
      hepatic abscess was performed. SM was identified in the content of the drain and
      selected antibiotic therapy with combination of tygecycline and TMP-SMX was
      immediately initiated.After 15 days of the selected therapy, the hepatic abscess
      and the left eye infection were completely resolved but unfortunately the patient
      reported permanent blindness. Discussion: Several studies identified most of the
      SM infections as nosocomial, however that can be excluded in this case because
      the patient presented signs of severe systemic infection 72 h before the
      hospitalization. The conservative treatment, with a combination of CT guided
      drainage and selected antibiotic therapy, gave good results. Conclusion: Although
      SM is thought to be a nosocomial pathogen, it can be involved in severe systemic
      sepsis affecting different organs outside the hospital setting. Fortunately, the
      combination of tigecycline with TMP-SMX seems to be the best therapeutic option.

PMID- 30237881
TI  - Gender disparity in epidemiological trend of HIV/AIDS infection and treatment in
      Ethiopia.
AB  - Background: The HIV/AIDS epidemic has been fuelled by gender inequality and
      disparity resulted in violation of women reproductive right. The "feminization"
      of the pandemic is more apparent in Sub-Saharan Africa where the larger numbers
      of HIV infected people are living. Although they carry the higher proportion of
      HIV cases; access to care and treatment is lower among women. In Ethiopia where
      HIV is prevalent and gender violence is common, the disparity may be higher.
      Therefore, this research aimed to assesses trends in gender disparity in the
      HIV/AIDS epidemic in Ethiopia to bring evidence for action. Methods: This study
      was conducted using aggregates of HIV/AIDS indicator data from 1990 to 2016 of
      UNAIDS data bases. The data was compiled and analyzed with excel and STATA
      Version 11. The trend was assessed, gender difference was measured and rate of
      change was compared between genders and specific age groups. Result: Adult
      females (age 15+) accounted 61.5% of the HIV cases and new infection among
      adults. While, adolescent females (age 10-19) and young women (age 15-24)
      accounted 52.3 and 57.5% of prevalent cases and 74 and 68% of new infection in
      their age category respectively. HIV is 1.62 times more prevalent among adult
      women than men. Since 1990, HIV cases among adults has risen markedly in the
      first decade with 24 and 20%, then declined by 41.5% in the second decade and
      rose again by 5 and 8.7% among women and men respectively. The overall prevalence
      is declined by 72.4 and 71.5% from the maximum record. Women and men have equal
      access for ART; 62% of men and 61% of women from all adults living with HIV were
      on ART. While 61% of deaths were among adult women and the death rate is similar
      among adolescent women and men. AIDS- related death has been declined by 76% from
      the maximum record. Conclusion: HIV/AIDS prevalence, new infection and AIDS
      related death are by far higher among adult women than men. While the coverage of
      treatment and HIV care is equal among both genders. Vulnerable age groups
      (adolescent females and young women) take the lion's share of the new infections
      and prevalent cases. Therefore due attention is needed to avert gender disparity
      with a particular emphasis for adolescents and young women.

PMID- 30237883
TI  - Transient elevation of squamous cell carcinoma antigen levels with influenza
      virus infection.
AB  - We report a case of squamous cell carcinoma antigen (SCCA) elevation due to
      influenza B infection. A 78-year-old male had undergone right middle lobectomy
      and lymphadenectomy for lung squamous cell carcinoma two years and four months
      previously. His SCCA level ranged from 0.8 ng/mL to 1.9 ng/mL after the surgery.
      He underwent blood testing, including SCCA, as part of a regular check-up three
      days after the diagnosis of the influenza B infection. His SCCA level was 17.1
      ng/mL; no recurrences were found on computed tomography. One month later, his
      SCCA level had decreased to 1.6 ng/mL. We should keep in mind that influenza
      infection may cause transient elevations in SCCA levels.

PMID- 30237884
TI  - Nintedanib prevented fibrosis progression and lung cancer growth in idiopathic
      pulmonary fibrosis.
AB  - A 76-year-old man with a past history of acute exacerbation (AE) and idiopathic
      pulmonary fibrosis (IPF) was treated with nintedanib because of decline in his
      forced vital capacity over time. A new small nodular lesion was visible on a
      computed tomography scan of the chest before initiation of nintedanib. Disease
      progression in IPF and change in size of the nodular lesion were not detected
      during administration of nintedanib. Nine months after starting nintedanib, the
      patient was diagnosed with acute gangrenous appendicitis, and nintedanib
      treatment was discontinued. The nodular lesion increased in size four months
      after the cessation of nintedanib. The nodular lesion was diagnosed as squamous
      cell carcinoma. In this case, nintedanib inhibited the disease progression of IPF
      and lung cancer simultaneously. Nintedanib may play an important role in the
      treatment of IPF-associated lung cancer.

PMID- 30237882
TI  - Aptamer-based search for correlates of plasma and serum water T2: implications
      for early metabolic dysregulation and metabolic syndrome.
AB  - Background: Metabolic syndrome is a cluster of abnormalities that increases the
      risk for type 2 diabetes and atherosclerosis. Plasma and serum water T2 from
      benchtop nuclear magnetic resonance relaxometry are early, global and practical
      biomarkers for metabolic syndrome and its underlying abnormalities. In a prior
      study, water T2 was analyzed against ~ 130 strategically selected proteins and
      metabolites to identify associations with insulin resistance, inflammation and
      dyslipidemia. In the current study, the analysis was broadened ten-fold using a
      modified aptamer (SOMAmer) library, enabling an unbiased search for new proteins
      correlated with water T2 and thus, metabolic health. Methods: Water T2
      measurements were recorded using fasting plasma and serum from non-diabetic human
      subjects. In parallel, plasma samples were analyzed using a SOMAscan assay that
      employed modified DNA aptamers to determine the relative concentrations of 1310
      proteins. A multi-step statistical analysis was performed to identify the
      biomarkers most predictive of water T2. The steps included Spearman rank
      correlation, followed by principal components analysis with variable clustering,
      random forests for biomarker selection, and regression trees for biomarker
      ranking. Results: The multi-step analysis unveiled five new proteins most
      predictive of water T2: hepatocyte growth factor, receptor tyrosine kinase FLT3,
      bone sialoprotein 2, glucokinase regulatory protein and endothelial cell-specific
      molecule 1. Three of the five strongest predictors of water T2 have been
      previously implicated in cardiometabolic diseases. Hepatocyte growth factor has
      been associated with incident type 2 diabetes, and endothelial cell specific
      molecule 1, with atherosclerosis in subjects with diabetes. Glucokinase
      regulatory protein plays a critical role in hepatic glucose uptake and metabolism
      and is a drug target for type 2 diabetes. By contrast, receptor tyrosine kinase
      FLT3 and bone sialoprotein 2 have not been previously associated with metabolic
      conditions. In addition to the five most predictive biomarkers, the analysis
      unveiled other strong correlates of water T2 that would not have been identified
      in a hypothesis-driven biomarker search. Conclusions: The identification of new
      proteins associated with water T2 demonstrates the value of this approach to
      biomarker discovery. It provides new insights into the metabolic significance of
      water T2 and the pathophysiology of metabolic syndrome.

PMID- 30237885
TI  - Congenital cystic adenomatoid malformation in adults detected after infection.
AB  - Congenital cystic adenomatoid malformation (CCAM) is a benign congenital tumour
      in which a part of the lung becomes polycystic. Case 1 was a 64-year-old male who
      was diagnosed with pneumonia, with multiple cysts in the right lower lung lobe,
      using chest computed tomography (CT). After treatment of the pneumonia, including
      Mycobacterium abscessus, a right lower lobectomy was performed. Case 2 was a 41
      year-old male who had suffered from pneumonia many times since his youth.
      Polycystic and infiltrative shadows were observed on chest CT. After treatment of
      the pneumonia, a right lower lobectomy was performed. Pathologically, both the
      cases were diagnosed as CCAM type 1. Although CCAM in adults is very rare, it
      should be considered in the differential diagnosis of cases with repeated
      pneumonia due to suspected congenital cystic disease. CCAM is better detectable
      with chest CT and requires active surgical treatment.

PMID- 30237886
TI  - Spontaneous fracture of indwelling pleural catheter.
AB  - Indwelling pleural catheters (IPCs) are increasingly used for the management of
      symptomatic malignant pleural effusion worldwide. IPCs have been documented to
      reduce the number of hospital bed days in patients with malignant pleural
      effusion and thus are often used as the preferred mode of management in fit
      healthy patients with good performance status. Complications related to IPCs,
      mainly in the form of pleural infection and needle tract metastasis, are well
      reported in the literature. Similarly, fracture of IPCs is a recognized
      complication during the process of IPC removal. We report the first ever case of
      spontaneous fracture of IPC in a patient with Stage IV lung cancer with malignant
      pleural effusion who was undergoing active chemotherapy and symptomatic
      management of the pleural effusion with an IPC.

PMID- 30237887
TI  - Management of rifampicin mono-resistant tuberculosis in Queensland, Australia: a
      retrospective case series.
AB  - Rifampicin mono-resistant tuberculosis (RMR-TB) is rare worldwide; however, it is
      associated with poor treatment outcomes. Evidence to guide the treatment of RMR
      TB is lacking. International guidelines have recently changed and now recommend
      that RMR-TB should be managed with multi-drug-resistant tuberculosis (MDR-TB)
      regimens. This report is a retrospective review of all cases of RMR-TB in
      Queensland, Australia, from 2000 to 2016 to assess treatment outcomes and
      regimens used. Twelve cases of RMR-TB were diagnosed, with seven patients
      completing treatment in Queensland. This study confirms that RMR-TB is rare in
      Queensland. Generally extended regimens with first-line agents +/- a
      fluoroquinolone were used, and all patients who completed treatment in Queensland
      had successful outcomes.

PMID- 30237888
TI  - Mycoplasma hominis empyema following caesarean section.
AB  - Mycoplasma hominis as a cause of empyema is rare. We report a case of empyema
      caused by M. hominis following a caesarean section. A 28-year-old woman at 39
      weeks and one day of pregnancy was admitted to our hospital and underwent an
      emergency caesarean section because of premature rupture of membranes. On
      postoperative day 2, she developed a fever, and flomoxef was administered. A
      pleural effusion developed on the right side. A diagnosis of empyema was made,
      and sulbactam/ampicillin was administered. However, the patient's clinical
      condition did not improve. Numerous small pinpoint colonies, which did not yield
      visible bacteria on a Gram stain, were observed on a plate of pleural fluid
      culture, and M. hominis empyema was suspected. Based on this result, antibiotic
      therapy was switched to clindamycin, and the patient's clinical condition
      improved rapidly. M. hominis was detected in the pleural fluid by polymerase
      chain reaction (PCR) assay. M. hominis should be considered a causative pathogen
      for empyema following a caesarean section.

PMID- 30237889
TI  - Persistent air leak successfully treated with endobronchial valves and digital
      drainage system.
AB  - A 62-year old man with severe chronic obstructive pulmonary disease developed a
      persistent air leak from an iatrogenic pneumothorax following Computed Tomography
      guided core biopsy of a pulmonary nodule. The pneumothorax was treated with an
      8.5F intercostal catheter, which was then replaced by a 28F thoracostomy tube
      after development of significant subcutaneous emphysema and a tension
      pneumothorax. The air leak showed no improvement until endobronchial valve (EBV)
      insertion guided by objective flow data from a digital drainage system (DDS). The
      air leak subsequently reduced with -20 cmH2O suction from the DDS, and the
      thoracostomy tube was removed once the objective measured flow rate had
      sufficiently diminished. The combination of EBV insertion and suction from the
      DDS successfully treated the persistent air leak, with timing of thoracostomy
      tube removal guided by DDS flow data.

PMID- 30237890
TI  - Multi-drug-resistant tuberculosis with galaxy and cluster signs on high
      resolution computed tomography.
AB  - The galaxy sign and cluster sign were first reported in pulmonary sarcoidosis.
      From those reports, these two signs became known as one of the characteristic
      computed tomography (CT) findings of sarcoidosis. We report a patient with
      pulmonary tuberculosis who had these two signs. A 44-year-old man was referred to
      our hospital for general fatigue, cough, and low-grade fever lasting about two
      months. Thoracic CT showed a large parenchymal nodule arising from coalescent
      small nodules (galaxy sign) and clusters composed of numerous small nodules
      (cluster sign) in the bilateral lungs. Three specimens of sputum acid-fast smear
      were negative. However, we performed a bronchoscopy, and Mycobacterium
      tuberculosis was proven to be positive by the acid-fast culture test of the
      obtained bronchoalveolar lavage fluid. Moreover, drug sensitivity testing
      revealed this to be a case of multi-drug-resistant tuberculosis. Patients with
      these signs must be examined carefully to differentiate tuberculosis from
      pulmonary sarcoidosis.

PMID- 30237891
TI  - Rapid emotional response and disadvantageous Iowa gambling task performance in
      women with borderline personality disorder.
AB  - Background: Adults with Borderline Personality Disorder (BPD) manifest poor
      performance on tasks of decision making which may be congruent with their
      decisional and interpersonal conflicts in real life. Poor decision making is
      often assumed to be due to impulsive behaviour or weak inhibitory control despite
      inconsistent evidences of these relationships, leaving questions about the
      specific nature of these decisional deficits. Decision making in BPD may be
      compromised by different domains of impulsivity, affective dysregulatory
      processes or unknown co-morbid ADHD which is considered a developmental precursor
      to BPD. Findings: Iowa Gambling Task (IGT) decision making, 2 tasks of inhibitory
      control and a self report of ADHD symptoms consisting of 9 subscales were
      administered to 41 BPD women and 41 healthy controls. No group differences in
      inhibitory control were present. Net decision making performance and all ADHD
      subscale ratings differed significantly among BPD women and healthy controls. BPD
      women did not meet the threshold indicative of moderate to severe ADHD. Three
      subscales of attention, behaviour/ disorganized and emotive were significantly
      associated with poor IGT performance in 26 women with BPD. Of these 3 variables,
      the emotive subscale, representing a rapid emotional response, was the only
      significant predictor contributing 49% to the variance in poor DM. Conclusions:
      This is the 1st evidence of an emotive type of impulsivity, representing a type
      of affective instability that is linked to poor IGT DM in BPD. Findings support
      the Somatic Marker Hypothesis of IGT DM and may reflect the affective
      dysregulation that characterizes the disorder.

PMID- 30237892
TI  - 14,15-epoxyeicosatrienoic acid produced by cytochrome P450s enhances neurite
      outgrowth of PC12 and rat hippocampal neuronal cells.
AB  - Polyunsaturated fatty acids, such as arachidonic acid, are accumulated in brain
      and induce neuronal differentiation. Arachidonic acid is metabolized to
      epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs) by
      cytochrome P450s. In this study, we found that 14,15-EET and 20-HETE-enhanced NGF
      induced rat pheochromocytoma PC12 cell neurite outgrowth even at the
      concentration of 100 nmol L-1. LC-MS analysis revealed that 14,15-EET was
      effectively produced from arachidonic acid by rat CYP2C11, 2C13, and 2C23, and
      these P450s were expressed in PC12 cells. An inhibitor of these P450s,
      ketoconazole, inhibited neurite outgrowth, whereas inhibition of soluble epoxide
      hydrolase, which hydrolyzes EETs to their corresponding diols enhanced neurite
      outgrowth. To determine the mechanism of neurite formation enhancement by
      arachidonic acid metabolites, we focused on transient receptor potential (TRP)
      channels expressed in PC12 cells. The TRPV4 inhibitor HC067047, but not the TRPV1
      inhibitor capsazepine, inhibited the effects of 14,15-EET on neurite outgrowth of
      PC12. Furthermore, 14,15-EET increased the cytosolic calcium ion concentration
      and this increase was inhibited by HC067047. 14,15-EET also enhanced neurite
      outgrowth of primary cultured neuron from rat hippocampus. This study suggests
      that arachidonic acid metabolites produced by P450 contribute to neurite
      outgrowth through calcium influx.

PMID- 30237893
TI  - Seroprevalence and trends of transfusion transmitted infections at Harar blood
      bank in Harari regional state, Eastern Ethiopia: eight years retrospective study.
AB  - Background: The use of unscreened blood exposes the patient to many transfusion
      transmitted infections including Hepatitis B Virus (HBV), Hepatitis C virus
      (HCV), Human Immunodeficiency Virus (HIV), and syphilis, among others. Thus,
      blood transfusion demands for meticulous pre-transfusion testing and screening.
      Trends of transfusion transmitted infections are important to take appropriate
      measures on blood bank services. Therefore the aim of this study was to assess
      seroprevalence and trends of transfusion transmitted infections at Harar blood
      bank in Harari regional state, Eastern Ethiopia from 2008 to 2015. Methods: A
      retrospective cross-sectional study was employed to review blood donors' history
      and laboratory tests records from November 16-December 31, 2017. All records of
      blood donors having vividly documented history and laboratory tests were reviewed
      by data collectors. All data were entered into EPI data version 3.1. It was
      exported and analyzed with Statistical Package for the Social Sciences version 16
      soft ware. Result: A total of 11, 382 blood donors' history and laboratory tests
      records were reviewed. Majority of them were males (82.6%), 57.6 % were in the
      age group of 17 to 25 years and 99.9% donors donated blood for the first time.
      The overall seroprevalence of transfusion transmitted infections (HBV, HIV, HCV
      and syphilis combined) was found to be 6.6%. The prevalence of HBV, HIV, HCV and
      syphilis were found to be 4.4%, 0.6%, 0.8% and 1.1%, respectively. The trend in
      prevalence of syphilis and HCV was statistical significant by year (p< 0.05).
      Those donors in the age group of 26-35 years (AOR: 2.1; 95% CI: 1.2,3.6), 36-45
      years (AOR: 4.1; 95% CI: 2.4,7.1) and greater than 46 years (AOR:4.6; 95% CI:
      2.3,9.1) were more likely to be infected with syphilis compared to the age group
      of 17-25 years. Male were more likely to be infected with HBV (AOR: 1.9; 95% CI:
      1.4, 2.5) than females. Conclusions: The magnitude of transfusion transmitted
      infections was lower than the previous studies conducted in Ethiopia. However,
      the decline in trends of transfusion transmitted infections has not been
      significant for some pathogens. Therefore, strict adherence with the criteria of
      preliminary blood donor selection should be implemented to reduce the amount of
      blood being withdrawn from transfusion after collection and screening.

PMID- 30237894
TI  - Diagnostic accuracy in field conditions of the sickle SCAN(r) rapid test for
      sickle cell disease among children and adults in two West African settings: the
      DREPATEST study.
AB  - Background: Sickle cell disease (SCD) accounts for 5% of mortality in African
      children aged < 5 years. Improving the care management and quality of life of
      patients with SCD requires a reliable diagnosis in resource-limited settings. We
      assessed the diagnostic accuracy of the rapid Sickle SCAN(r) point-of-care (POC)
      test for SCD used in field conditions in two West-African countries. Methods: We
      conducted a case-control study in Bamako (Mali) and Lome (Togo). Known cases of
      sickle cell disease (HbSS, HbSC), trait (HbAS), HbC heterozygotes (HbAC) and
      homozygous (HbCC), aged >=6 months were compared to Controls (HbAA), recruited by
      convenience. All subjects received both an index rapid POC test and a gold
      standard (high-performance liquid chromatography in Bamako; capillary
      electrophoresis in Lome). Personnel conducting tests were blinded from subjects'
      SCD status. Sensitivity and specificity were calculated for each phenotype.
      Practicality was assessed by local healthcare professionals familiar with
      national diagnostic methods and their associated constraints. Results: In Togo,
      209 Cases (45 HbAS, 39 HbAC, 41 HbSS, 44 HbSC and 40 HbCC phenotypes) were
      compared to 86 Controls (HbAA). 100% sensitivity and specificity were observed
      for AA Controls and HbCC cases. Estimated sensitivity was 97.7% [95% confidence
      interval: 88.0-99.9], 97.6% [87.1-99.9%], 95.6% [84.8-99.5%], and 94.9% [82.7
      99.4], for HbSC, HbSS, HbAS, and HbAC, respectively. Specificity exceeded 99.2%
      for all phenotypes. Among 160 cases and 80 controls in Mali, rapid testing was
      100% sensitive and specific. Rapid testing was well accepted by local healthcare
      professionals. Conclusion: Rapid POC testing is 100% accurate for homozygote
      healthy people and excellent (Togo) or perfect (Mali) for sickle cell trait and
      disease patients. In addition to its comparable diagnostic performance, this test
      is cheaper, easier to implement, and logistically more convenient than the
      current standard diagnostic methods in use. Its predictive value indicators and
      diagnostic accuracy in newborns should be further evaluated prior to
      implementation in large-scale screening programs in resource-limited settings
      where SCD is prevalent.

PMID- 30237895
TI  - Biochemical and hematological changes among anemic and non-anemic pregnant women
      attending antenatal clinic at the Bolgatanga regional hospital, Ghana.
AB  - Background: Anemia in pregnancy may not only be associated with maternal
      morbidity and mortality but can also be detrimental to the fetus. A definitive
      diagnosis of anemia is a pre-requisite to unravelling possible cause(s), to allow
      appropriate treatment intervention. It is hypothesised that measured hemoglobin
      (HGB), complemented by biochemical and other hematological parameters would
      enhance anemia diagnosis. Methods: This was a cross-sectional study among 400
      pregnant women comprising 253 anemic and 147 non-anemic pregnant women, attending
      an antenatal clinic at Bolgatanga Regional Hospital, Ghana. Venous blood was
      collected and hemoglobin genotype, complete blood count and biochemical
      parameters [ferritin, iron, total iron binding capacity (TIBC), transferrin
      saturation (TfS), C-reactive protein (CRP) and bilirubin] were determined. Thick
      blood films were prepared for malaria parasitemia, while early morning stool and
      midstream urine samples were examined for enteric and urogenital parasites,
      respectively. Results: There were significantly reduced levels of HGB (p <
      0.0001), HCT (p < 0.0001), MCV (p < 0.0001), iron (0.0273), ferritin (p = 0.018)
      and transferrin saturation (0.0391) and increased WBC (p = 0.006), RDW (p =
      0.0480), TIBC (p = 0.0438) and positivity of CRP in anemic, compared to non
      anemic pregnant women. Anemic women were associated with increased proportion of
      hemoglobinopathies (AS, SS and SC), Plasmodium falciparum, Schistosoma hematobium
      and intestinal parasite infections. Conclusion: Anemic pregnant women are
      associated with a significant derangement in hematological and iron indices that
      implicate iron deficiency. This was influenced by hemoglobinopathies and
      parasitic infections.

PMID- 30237896
TI  - The fortification method relying on assumed human milk composition overestimates
      the actual energy and macronutrient intakes in very preterm infants.
AB  - Background: To achieve recommended nutrient intakes in preterm infants, the
      target fortification method of human milk (HM) was proposed as an alternative to
      standard fortification method. We aimed to compare assumed energy and
      macronutrient intakes based on standard fortified HM with actual intakes relying
      on measured composition of human milk (HM), in a cohort of HM-fed very preterm
      infants. Methods: This study is a secondary retrospective analysis, in which
      assumed energy and macronutrient contents of daily pools of own mother's milk
      (OMM) from 33 mothers and donated HM (DHM) delivered to infants were compared
      with the measured values using a mid-infrared HM analyzer. A fortification method
      consisting of modular protein and/or fat supplements added to standard fortified
      HM was used to provide the minimum recommended daily intakes of energy 110
      Kcal/kg and protein up to 4.0 g/kg. Assumed nutrient intakes were compared with
      actual nutrient intakes from full enteral feeding to 35 weeks plus 6 days
      postmenstrual age, using the Wilcoxon matched-pairs signed ranks test. Results:
      The composition of 1181 samples of daily pools of HM were measured. For 90.2% of
      study days, infants were exclusively fed OMM and in remaining days fed OMM plus
      DHM. Comparing with reported preterm OMM composition, measured protein
      concentration was significantly lower, and energy and other macronutrient
      concentrations were lower only from the second to third postnatal week. Using
      fortified HM, the actual median daily intakes of energy, protein, and fat were
      significantly lower (113.3 vs. 120.7 Kcal/kg, 4.45 vs. 4.73 g/kg, and 4.96 vs.
      5.35 g/kg, respectively) and the actual protein-to-energy ratio (PER)
      significantly higher than what was assumed (4.2 vs. 4.0), without differences in
      carbohydrate intake. Conclusions: When fortifying the HM, we used conservative
      target intakes trying not to exceed the osmolarity recommended for infant feeds.
      Actual energy, protein and fat intakes in OMM were significantly lower than
      assumed. This resulted in inadequate intake using our fortification method, that
      did not compensate the suboptimal measured energy and macronutrient contents of
      OMM delivered. Further studies comparing assumed with the gold standard target
      fortification are needed to determine safe upper limits of assumed fortification.

PMID- 30237897
TI  - Mechanical texture profile of Hanwoo muscles as a function of heating
      temperatures.
AB  - Background: Cooking temperature and consequently doneness of beef muscles are
      most important for the palatability and consumer acceptability. Current study
      assessed the response of mechanical texture of Hanwoo muscles as a function of
      cooking temperature at different ageing days. Six muscles (Psoas major (PM),
      Longissimus thoracics (LT), Gluteus medius (GM), Semimembranosus (SM), Biceps
      femoris (BF) and Triceps brachii (TB)) were collected from each 10 Hanwoo steers.
      Warner-Bratzler WB-shear force (WBSF) and texture profile analysis (TPA) texture
      profiles were determined after 3 or 21 days of chiller, and randomly assigned to
      four groups; non-cooked, cooked at 55, 70 or 85  degrees C. Results: Toughness of
      WBSF and TPA hardness of Hanwoo muscles were presence in the order of LT = PM =
      GM = SM < BF = TB (p < 0.001) for non-cooked raw muscle, and PM < LT = GM = SM <
      TB=BF (p < 0.001) for cooked meat aged for 3 days. WBSF linearly increased in 3
      days aged meats after cooked at a higher temperature (P < 0.05). On the other
      hand, toughening of the muscles were significantly (P < 0.05) differed at various
      temperature when muscles were aged for 21 days. WBSF of PM and LT muscles were
      significantly increased at a higher cooking temperature, while other muscles
      (i.e., GM, SM, BF, TB) showed the lowest values at 70  degrees C. In the case of
      TPA hardness, the effect of cooking temperature was very less in the toughness of
      the muscle (P > 0.05). Conclusion: Taken together, these findings clearly showed
      that the toughness of the muscle highly depends and varies upon the temperature
      and ageing of the muscle. Moreover, the effect of cooking temperature was very
      limited on aged muscles. The results mirror the importance of cooking temperature
      for objective measurements which ultimately estimate sensory tenderness and other
      quality traits.

PMID- 30237898
TI  - Molecular surveillance of respiratory viruses with bioaerosol sampling in an
      airport.
AB  - Recognizing that crowded, high-traffic airports and airplanes have been
      implicated in respiratory disease transmission, we partnered with administrators
      of Raleigh Durham International Airport (RDU) in conducting a pilot study of
      aerosol surveillance for respiratory viruses at RDU. From January to March 2018
      we used NIOSH 2-stage samplers to collect 150 min aerosol samples in crowded
      areas at RDU. Four (17%) of the 24 samples were positive for known respiratory
      pathogens including influenza D virus and adenovirus. These results suggest the
      feasibility of employing bioaerosol surveillance techniques in public
      transportation areas, such as airports, as a noninvasive way to detect and
      characterize novel respiratory viruses.

PMID- 30237899
TI  - Development, acceptability and feasibility of a communication skills training
      package for therapeutic radiographers to reduce fear of recurrence development in
      breast cancer patients (FORECAST2).
AB  - Background: Many patients who have been treated for breast cancer experience high
      levels of fear that the cancer will return. The FORECAST pilot study showed that
      for a third of the patients, fears of cancer recurrence (FCR) increase during
      radiotherapy treatment and that conversations with their therapeutic radiographer
      at the weekly review meetings might help patients manage these concerns. This
      study aims to develop a communication skills training package (KEW, for 'Know',
      'Encourage' and 'Warm-up') for therapeutic radiographers based on the findings of
      the FORECAST pilot study and on active input from patients and radiographers.
      This package will be piloted in a single centre to evaluate its acceptability and
      to prepare for a multi-centre clinical trial. Methods: The study consists of
      three phases. In the first phase, patient representatives and therapeutic
      radiographers participate in Experience-Based Co-Design to identify ways to
      improve communication during the radiotherapy review. In the second phase,
      various stakeholders, including members of the Society of Radiographers and of
      national patient representation groups, are consulted to develop a storyboard for
      the production of the communication training package. In the third phase, the
      acceptability and feasibility of the training is evaluated through observations,
      recruitment rates and follow-up discussions; a fidelity measure is designed; and
      potential benefits are observed, with patients' fear of cancer recurrence (FCR7)
      as the primary outcome. Secondary outcomes include a short daily measure of
      recurrence (FCR3), patients' positive and negative affect (PANAS), perceived
      empathy from the radiographer (CARE), satisfaction with the review meetings
      (RISS) and health-related quality of life (EQ-5D-3L). Discussion: To date, there
      has been limited research on how communication between therapeutic radiographers
      and patients during review appointments can help to manage patients' recurrence
      fears during radiotherapy treatment. A collaborative and participatory approach
      to the development of a communication skills training will ensure that it is
      optimally targeted to the needs and preferences of both patients and
      radiographers. Targeting recurrence fears through communication at this stage,
      when patients are still in regular contact with healthcare providers, has the
      potential to reduce the need for complex interventions post-treatment. Trial
      registration: NRES reference: 18/LO/0669. Clinicaltrial.gov ID: NCT03468881.

PMID- 30237901
TI  - Female genital mutilation in the UK- where are we, where do we go next? Involving
      communities in setting the research agenda.
AB  - Background: Female Genital Mutilation (FGM) is all practices involving cutting,
      alteration or injury to the female genitalia for non-medical reasons. It is a
      form of violence against women and children, with no benefits and many harms. In
      2014, the UK Government committed to working to eliminate FGM. Steps taken
      towards this aim included creation of educational and safeguarding resources for
      professionals, and legislative changes including a mandatory reporting duty for
      professionals in England and Wales (where if a girl under 18 discloses or is
      found on examination to have FGM then the professional is mandated to report this
      to the police), and an FGM Enhanced Dataset applicable to NHS organisations in
      England requiring the submission of personal data about women and girls who have
      had FGM to NHS Digital. To date, compliance with dataset returns from primary
      care services have been low. This report describes using patient and public
      involvement (PPI) to identify research and service priorities to support
      communities affected by FGM. Methods: We held a series of PPI events (4 focus
      groups, and a multi-agency seminar) in 2015-2016, following the introduction of
      these legislative changes, speaking to community members, and professionals
      involved in their care. We asked participants to consider what they identified as
      research, knowledge and service priorities to support communities affected by
      FGM. Results: The impact of these legislative and reporting requirements on the
      trust needed for community members to seek to consult health services was
      identified as important for further research. Priorities for service development
      were holistic services, that met a woman's needs throughout her lifecourse.
      Participants emphasised the importance of understanding how to listen, involve
      and utilise community voices in developing education for professionals, designing
      services, and developing policy. Conclusions: There was a desire for change to
      develop from within affected communities; any learning and resources need to be
      co-created and constructed in such a way that they can be effectively shared
      between women, communities, and professionals. Questions remain about how to
      define community consultation, how to recognise when it was adequate, and how to
      hear beyond community activists to hear a wider range of voices.

PMID- 30237900
TI  - Apolipoprotein A1 mimetic peptide ATI-5261 reverses arterial stiffness at late
      pregnancy and early postpartum in a COMT-/- mouse model of preeclampsia.
AB  - Background: Preeclampsia (PE) is a serious maternal complication during
      pregnancy. Associated arterial stiffness in PE patients leads to increased risks
      of cardiovascular diseases later in life. Cholesterol efflux capacity, especially
      ATP binding cassette transporter A1 (ABCA1) dependent capacity, has been proposed
      to be a likely mediator of arterial stiffness. In the present study, we aimed to
      evaluate the effect of an apolipoprotein A1 mimetic peptide ATI-5261 on arterial
      stiffness in a mouse model of PE. Methods: Pregnant COMT-/- mice were randomized
      to receive vehicle or ATI-5261 (30 mg/kg per day) via subcutaneous injection from
      gestational days (GD) 10.5 to GD 18.5 or to 10 days postpartum. Pregnant C57BL/6
      J mice received vehicle during paralleled periods were served as normal controls.
      Results: COMT-/- mice displayed maternal hypertension and proteinuria during
      pregnancy. Carotid-femoral pulse wave velocity (PWV) was increased at GD 18.5 and
      10 days postpartum. ATI-5261 treatment in COMT-/- mice significantly reduced PWV
      and partially normalized impaired ex vivo vascular function at late pregnancy and
      early postpartum. ATI-5261 treatment also increased serum ABCA1 concentrations
      and cholesterol efflux capacity, as well as ABCA1 expressions in the placenta.
      Pup weights, crown to rump lengths and abdominal circumferences were reduced in
      COMT-/- mice. Treatment with ATI-5261 did not alter these fetal measurements but
      significantly reduced placental weights and increased fetal to placental ratios
      in COMT-/- mice. Conclusion: ATI-5261 reversed arterial stiffness at late
      pregnancy and early postpartum in a COMT-/- mouse model of PE and may be a
      potential therapy for arterial stiffness associated with PE.

PMID- 30237902
TI  - Update on unicompartmental knee arthroplasty: Current indications and failure
      modes.
AB  - Despite the excellent success rates of modern implants, unicompartmental knee
      arthroplasty (UKA) continues to show relatively high failure and revision rates,
      especially when compared with total knee arthroplasty (TKA).These higher rates of
      failure and revision are mainly observed during the early (< 5 years) post
      operative period and are often due to incorrect indications and/or surgical
      errors.The correct clinical and radiological indications for UKA have therefore
      been analysed and correlated as far as possible with the principal mechanisms and
      timing of failures of UKA. Cite this article: EFORT Open Rev 2018;3:442-448. DOI:
      10.1302/2058-5241.3.170060.

PMID- 30237903
TI  - Correlation between skin and bone parameters in women with postmenopausal
      osteoporosis: A systematic review.
AB  - Skin and bone share similarities in terms of biochemical composition.Some authors
      have hypothesized that their properties could evolve concomitantly with age,
      allowing the estimation of the parameters of one from those of the other.We
      performed a systematic review of studies reporting the correlation between skin
      and bone parameters in women with postmenopausal osteoporosis.Fourteen studies -
      including 1974 patients - were included in the review.Three of these studies
      included two groups of participants - osteoporotic and non-osteoporotic - in
      order to compare skin parameters between them: two studies found a significant
      difference between the two groups and one did not.Eleven of these studies
      included one population of interest and compared its skin and bone parameters in
      a continuous manner: eight studies compared dermal thickness to bone mineral
      density (seven found a significant correlation [R = 0.19-0.486] and one did not);
      two studies compared skin elasticity to bone mineral density (both found a
      significant correlation [R = 0.44-0.57); and one study compared skin collagen to
      bone mineral density and found a significant correlation (R = 0.587).It can be
      assumed that the estimation of skin alterations from ageing could help in
      estimating concomitant bone alterations. Cite this article: EFORT Open Rev
      2018;3:449-460. DOI: 10.1302/2058-5241.3.160088.

PMID- 30237904
TI  - Chronic pain after total knee arthroplasty.
AB  - Despite a good outcome for many patients, approximately 20% of patients
      experience chronic pain after total knee arthroplasty (TKA).Chronic pain after
      TKA can affect all dimensions of health-related quality of life, and is
      associated with functional limitations, pain-related distress, depression, poorer
      general health and social isolation.In both clinical and research settings, the
      approach to assessing chronic pain after TKA needs to be in-depth and
      multidimensional to understand the characteristics and impact of this pain.
      Assessment of this pain has been inadequate in the past, but there are
      encouraging trends for increased use of validated patient-reported outcome
      measures.Risk factors for chronic pain after TKA can be considered as those
      present before surgery, intraoperatively or in the acute postoperative period.
      Knowledge of risk factors is important to guide the development of interventions
      and to help to target care. Evaluations of preoperative interventions which
      optimize pain management and general health around the time of surgery are
      needed.The causes of chronic pain after TKA are not yet fully understood,
      although research interest is growing and it is evident that this pain has a
      multifactorial aetiology, with a wide range of possible biological, surgical and
      psychosocial factors that can influence pain outcomes.Treatment of chronic pain
      after TKA is challenging, and evaluation of combined treatments and individually
      targeted treatments matched to patient characteristics is advocated. To ensure
      that optimal care is provided to patients, the clinical- and cost-effectiveness
      of multidisciplinary and individualized interventions should be evaluated. Cite
      this article: EFORT Open Rev 2018;3:461-470. DOI: 10.1302/2058-5241.3.180004.

PMID- 30237907
TI  - Health system barriers and levers in implementation of the Expanded Program on
      Immunization (EPI) in Pakistan: an evidence informed situation analysis.
AB  - Background: In Pakistan, immunization coverage has been quite low since the
      program's inception, and the 2012-2013 population-based survey recorded it at
      54%. Much has been written about the issues, challenges, and constraints in the
      implementation of Pakistan's immunization program. However, there is a need to
      better understand the health system barriers as well as levers that influence
      progress. This review aims to bridge the information gaps on system-level
      barriers that currently impede the optimal delivery and uptake of immunization
      services to the children of Pakistan through the Expanded Program on Immunization
      (EPI). Methods: We conducted a comprehensive literature review, using PubMed and
      Google Scholar to find peer-reviewed literature, and also reviewed EPI-related
      international and national reports. Additionally, we consulted government
      reports, surveys, and publications on the health system. Employing the basic
      tenets of WHO's health systems framework for health system strengthening, and a
      socio-ecological model, this study cataloged the service delivery and the demand
      side perspective on various pillars of Pakistan's immunization program. Results:
      Themes generated from the literature review included financing, governance,
      service delivery, human resources, information systems, and supplies and
      vaccines. Findings suggest that certain areas in the larger health system need to
      be improved for a more coordinated implementation of EPI in Pakistan. Moreover,
      it is imperative to understand community behaviors and perceptions as well as
      demand side issues in order to achieve the desired results. Conclusion: For
      better immunization coverage and ultimately a reduction in child mortality due to
      preventable diseases, EPI operations and performance must be improved. Further
      systematic implementation research could help to develop an even finer
      understanding of the system-wide bottlenecks encumbering the coverage and
      efficiency of the program.

PMID- 30237906
TI  - Plantar fasciopathy: A current concepts review.
AB  - Plantar fasciopathy is very prevalent, affecting one in ten people in their
      lifetime.Around 90% of cases will resolve within 12 months with conservative
      treatment.Gastrocnemius tightness has been associated with dorsiflexion stiffness
      of the ankle and plantar fascia injury.The use of eccentric calf stretching with
      additional stretches for the fascia is possibly the non-operative treatment of
      choice for chronic plantar fasciopathy.Medial open release of approximately the
      medial third of the fascia and release of the first branch of the lateral plantar
      nerve has been the most accepted surgical treatment for years.Isolated proximal
      medial gastrocnemius release has been reported for refractory plantar fasciopathy
      with excellent results and none of the complications of plantar fasciotomy. Cite
      this article: EFORT Open Rev 2018;3:485-493. DOI: 10.1302/2058-5241.3.170080.

PMID- 30237905
TI  - Swellings of the sternoclavicular joint: review of traumatic and non-traumatic
      pathologies.
AB  - The sternoclavicular joint (SCJ) is an integral part of the shoulder girdle that
      connects the upper limb to the axial skeleton.Swelling of the SCJ is commonly due
      to trauma, degeneration, infections and other disease processes that affect
      synovial joints.This review also focuses on uncommon conditions that could affect
      the SCJ, including SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis)
      syndrome, Friedrich's disease and Tietze syndrome.The scope of this review is
      limited to the analysis of the current evidence on the various conditions
      affecting the SCJ and also to provide an algorithm to manage these conditions.
      Cite this article: EFORT Open Rev 2018;3:471-484. DOI: 10.1302/2058
      5241.3.170078.

PMID- 30237908
TI  - Model application niche analysis: Assessing the transferability and
      generalizability of ecological models.
AB  - The use of models by ecologists and environmental managers, to inform
      environmental management and decision-making, has grown exponentially in the past
      50 years. Due to logistical, economical, and theoretical benefits, model users
      frequently transfer preexisting models to new sites where data are scarce.
      Modelers have made significant progress in understanding how to improve model
      generalizability during model development. However, models are always imperfect
      representations of systems and are constrained by the contextual frameworks used
      during their development. Thus, model users need better ways to evaluate the
      possibility of unintentional misapplication when transferring models to new
      sites. We propose a method of describing a model's application niche for use
      during the model selection process. Using this method, model users synthesize
      information from databases, past studies, and/or past model transfers to create
      model performance curves and heat maps. We demonstrated this method using an
      empirical model developed to predict the ecological condition of plant
      communities in riverine wetlands of the Appalachian Highland physiographic
      region, U.S.A. We assessed this model's transferability and generalizability
      across (1) riverine wetlands in the contiguous U.S.A., (2) wetland types in the
      Appalachian Highland physiographic region, and (3) wetland types in the
      contiguous U.S.A. With this methodology and a discussion of its critical steps,
      we set the stage for further inquiries into the development of consistent and
      transparent practices for model selection when transferring a model.

PMID- 30237911
TI  - Fasciotomy for Chronic Exertional Compartment Syndrome of the Leg.
AB  - Surgical release of the anterior and lateral compartments of the lower leg has
      been shown to relieve the symptoms of chronic exertional compartment syndrome. We
      utilize a technique that allows the surgeon to perform anterior and lateral
      compartment fasciotomies through a single incision while safely identifying the
      superficial peroneal nerve. After positioning the patient supine on the operating
      table with the operative extremity prepared and draped, anatomic landmarks are
      identified on the patient's skin. The major steps of the procedure are (1)
      identifying the distal end of the fibula, anterior fibular diaphysis, tibial
      crest, fibular head, and lateral aspect of the patella; (2) drawing the skin
      incision, beginning 6 to 8 cm proximal to the distal end of the fibula centered
      between the tibial crest and anterior fibular diaphysis and extending it 6 cm
      proximally; (3) making a skin incision longitudinally and dissecting the
      subcutaneous tissue to allow identification of the fascia and superficial
      peroneal nerve; (4) performing gentle neurolysis; (5) identifying the anterior
      and lateral compartments, making small incisions in the fascia of each
      compartment, and then performing fasciotomy of the lateral and then anterior
      compartments while protecting the superficial peroneal nerve; and (6) irrigating
      the wound, closing it in layers, and applying a soft, compressive dressing.
      Postoperatively, the patient is allowed to bear as much weight as he or she can
      tolerate. Current literature indicates that good-to-excellent outcomes can be
      expected for 90% to 95% of patients treated with fasciotomy. Military personnel
      and patients with posterior compartment involvement may have less reliable
      outcomes.

PMID- 30237909
TI  - The Human Interface of Biomedical Informatics.
AB  - Biomedical informatics is the science of information, where information is
      defined as data with meaning. This definition identifies a fundamental challenge
      for informaticians: connecting with the healthcare team by enabling the
      acquisition, retrieval, and processing of information within the cognitive
      capabilities of the human brain. Informaticians can become aware of the
      constraints involved with cognitive processing and with workplace factors that
      impact how information is acquired and used to facilitate an improved user
      interface providing information to healthcare teams. Constraints affecting
      persons in the work environment include as follows: (1) cognitive processing of
      information; (2) cognitive load and memory capacity; (3) stress-affecting
      cognition; (4) cognitive distraction, attention, and multitasking; (5) cognitive
      bias and flexibility; (6) communication barriers; and (7) workplace environment.
      The human brain has a finite cognitive load capacity for processing new
      information. Short-term memory has limited throughput for processing of new
      informational items, while long-term memory supplies immediate simultaneous
      access to multiple informational items. Visual long-term memories can be
      extensive and detailed. Attention may be task dependent and highly variable among
      persons and requires maintaining control over distracting information.
      Multitasking reduces the effectiveness of working memory applied to each task.
      Transfer of information from person to person, or machine to person, is subject
      to cognitive bias and environmental stressors. High-stress levels increase
      emotional arousal to reduce memory formation and retrieval. The workplace
      environment can impact cognitive processes and stress, so maintaining civility
      augments cognitive abilities. Examples of human-computer interfaces employing
      principles of cognitive informatics inform design of systems to enhance the user
      interface.

PMID- 30237910
TI  - Magnetic resonance multitasking for motion-resolved quantitative cardiovascular
      imaging.
AB  - Quantitative cardiovascular magnetic resonance (CMR) imaging can be used to
      characterize fibrosis, oedema, ischaemia, inflammation and other disease
      conditions. However, the need to reduce artefacts arising from body motion
      through a combination of electrocardiography (ECG) control, respiration control,
      and contrast-weighting selection makes CMR exams lengthy. Here, we show that
      physiological motions and other dynamic processes can be conceptualized as
      multiple time dimensions that can be resolved via low-rank tensor imaging,
      allowing for motion-resolved quantitative imaging with up to four time
      dimensions. This continuous-acquisition approach, which we name cardiovascular MR
      multitasking, captures - rather than avoids - motion, relaxation and other
      dynamics to efficiently perform quantitative CMR without the use of ECG
      triggering or breath holds. We demonstrate that CMR multitasking allows for T1
      mapping, T1-T2 mapping and time-resolved T1 mapping of myocardial perfusion
      without ECG information and/or in free-breathing conditions. CMR multitasking may
      provide a foundation for the development of setup-free CMR imaging for the
      quantitative evaluation of cardiovascular health.

PMID- 30237912
TI  - Lengthening of the Femur with a Remote-Controlled Magnetic Intramedullary Nail:
      Antegrade Technique.
AB  - Introduction: Femoral lengthening with an intramedullary nail avoids the need for
      external fixation with its inherent challenges. Indications and
      Contraindications:  Step 1 Preoperative Planning: Determine the location of the
      osteotomy, which should be at the apex of the deformity or at the natural
      anterior bow of the femur, as well as the length and type of nail, which must be
      ordered a few weeks in advance. Step 2 Operating Room Setup: Position the patient
      supine on a flat radiolucent table; the goal is access for antegrade canal
      reaming and nail insertion. Step 3 Part 1 of the Osteotomy Multiple Percutaneous
      Drill-Holes: Begin the osteotomy by making multiple percutaneous drill-holes,
      thereby avoiding the soft-tissue stripping and heat necrosis associated with the
      use of a power saw. Step 4 Entry Into the Proximal Part of the Medullary Canal:
      Use a minimal incision approach to the proximal part of the medullary canal. Step
      5 Preparation of the Medullary Canal and Insertion of Rotational Markers: Ream
      the medullary canal of the intact bone over a guidewire; mark the rotation before
      the osteotomy is complete. Step 6 Insertion of the Nail and Part 2 of the
      Osteotomy: Insert the internal lengthening nail in an antegrade direction up to
      the osteotomy location, complete the osteotomy, and pass the nail across the
      osteotomy site. Step 7 Insertion of Locking Screws: Insert proximal and distal
      interlocking screws. Step 8 Release of the Iliotibial Band: To prevent knee
      stiffness, release the iliotibial band through a 3-cm lateral incision, which is
      usually made by connecting the two stab wounds created for the distal
      interlocking screws. Step 9 Marking the Magnet Location: Mark the magnet location
      in the implant on the skin to enable use of the remote control. Step 10
      Postoperative Care: Postoperative management entails limited weight-bearing,
      distraction, and range-of-motion exercises. Results: Femoral lengthening with the
      remote-controlled magnetic intramedullary nail has had excellent clinical
      efficacy. Pitfalls and Challenges: 

PMID- 30237913
TI  - Lumbar Microdiscectomy.
AB  - In most patients, the radiculopathy associated with lumbar disc herniation
      resolves nonoperatively. For patients in whom nonsurgical management has failed,
      microdiscectomy can be considered. Today, an operating microscope is preferred
      because of the collinear light and magnification offered. Alternatively, loupes
      and a headlight may be employed. The major steps of the procedure are (1) making
      a 2-cm vertical incision and then developing the corridor to the lamina
      subperiosteally or by using serial dilation techniques; (2) confirming the level
      of surgery radiographically prior to incision and once the lamina has been
      reached and then detaching the lateral attachments of the flavum; (3) making a
      small laminotomy, resecting any superior facet osteophytes, then mobilizing the
      compressed traversing nerve root, and, in some cases, making a small annulotomy;
      and (4) removing loose disc fragments and performing wound closure. Most outcomes
      reports after microdiscectomy have been favorable for radicular symptoms.
      Associated back pain typically decreased as well. Common complications include
      recurrent disc herniation or disc herniation at another level, wound infections,
      and durotomy with spinal headache.

PMID- 30237914
TI  - Resurfaced Allograft-Prosthetic Composite for Proximal Tibial Reconstruction in
      Children.
AB  - Introduction: Reconstruction of the proximal part of the tibia in children with
      use of an unconstrained tibial component cemented in an allograft-prosthetic
      composite after proximal tibial resection spares the distal femoral physis and
      articular cartilage, maintains the bone stock of the tibia, and allows the
      allograft to be adapted to the small tibial dimension in very young patients.
      Step 1 Make the Incision: Make a longitudinal incision medially or laterally,
      depending on the side of the biopsy (usually medial), encompassing and encircling
      the biopsy site. Step 2 Perform the Arthrotomy: A parapatellar arthrotomy is
      performed, and the cruciate ligaments are cut close to the femoral attachment.
      Step 3 Isolate the Vascular Bundle: Retract the medial gastrocnemius muscle and
      then isolate and protect the popliteal and posterior tibial vessels. Step 4
      Perform an Osteotomy of the Tibia: Perform an osteotomy of the tibiofibular joint
      and the tibial shaft at the appropriate level as determined on the basis of the
      preoperative imaging, and then complete the resection. Step 5 Prepare the
      Allograft on a Separate Table: Cut and prepare the allograft according to the
      specimen dimensions. Step 6 Prepare the Composite Device: Cement the tibial
      component of an unconstrained total knee prosthesis in the allograft and place
      the trial device. Step 7 Fix the Composite Device and Suture the Capsule and
      Ligaments: Place the trial composite device and then fix the composite device to
      the host tibia and suture the capsule and ligaments. Step 8 Postoperative Care:
      Immobilize the knee with an above-the-knee plaster cast, which is worn for six
      weeks, and then have the patient perform progressive functional rehabilitation.
      Results: The rate of postoperative infection after proximal tibial reconstruction
      with a resurfaced allograft composite in children has been found to be no higher
      than that with other reconstructive techniques for the proximal part of the
      tibia; our series had a 5% rate of deep
      infection.IndicationsContraindicationsPitfalls & Challenges.

PMID- 30237915
TI  - Posterior Mini-Incision Approach for Total Hip Replacement.
AB  - We developed a modification of the posterior mini-incision for total hip
      arthroplasty, which was initially used by Sculco at The Hospital for Special
      Surgery, in response to the movement in the orthopaedic community to perform
      total hip arthroplasty with smaller incisions. Our approach preserves the
      piriformis and quadratus femoris muscles of the external rotators, uses three
      incisions into the capsule but does not excise the capsule, does not incise the
      tensor fascia/iliotibial band, and leaves intact the insertion of the gluteus
      maximus onto the femur. We have used this incision since 2004, and our published
      results and those of others show that the greatest advantage is cosmetic and
      patients' perception of less violation of their body. It is a contributor to the
      same-day surgery program and rapid recovery protocol on which we have reported.
      The steps of the procedure include (1) an incision made along the posterior edge
      of the greater trochanter from the level of the vastus tubercle to one
      fingerbreadth from the tip of the greater trochanter; (2) a deep L-shaped
      incision parallel to the piriformis tendon, and along the posterior edge of the
      greater trochanter through the small external rotator muscles and hip capsule to
      the proximal edge of the quadratus to expose the femoral head and neck; (3)
      measurement of the neck cut from the distal edge of the femoral head and
      amputation of the femoral head; (4) exposure of the cut neck of the femur with
      retractors and broaching of the femur; (5) exposure of the acetabulum with
      retractors and acetabular reaming to prepare it for the cup; (6) implantation of
      the cup and stem and a femoral head of the correct length to restore lower-limb
      length and offset; and (7) closure of the wound in layers with the skin with
      subcutaneous sutures and sealing of the wound with a DERMABOND dressing
      (Ethicon). The expected outcome is that the patient will walk with full weight
      bearing on the day of the operation and be discharged home that day or the next.
      Patients with occupations that do not require physical labor can return to work
      in one week, and according to our data 98% of patients under sixty-five can walk
      one mile (1.6 km) by three weeks. Recovery is in three phases: for the first
      month, the patient has soreness and swelling from the surgical trauma to the
      tissues; at three months, the muscles are well healed; and at six months, bone
      healing is mature. The hip is "forgotten" (the patient goes days without thinking
      about it) after six months.

PMID- 30237917
TI  - Diagnostic Knee Arthroscopy and Partial Meniscectomy.
AB  - Knee arthroscopy is the most commonly performed orthopaedic procedure in the
      United States. Indications have grown exponentially since the procedure was first
      popularized by Watanabe and Jackson. Treatment of meniscal tears is the most
      common reason for knee arthroscopy, with approximately 700,000 arthroscopic
      partial meniscectomies performed annually. Other indications include assistance
      for cruciate ligament reconstruction, osteochondral lesions, removal of loose
      bodies, synovectomy, and septic arthritis. Arthroscopy is accomplished with the
      use of two small incisions on either side of the patella at the anterior aspect
      of the knee. An arthroscope is inserted through one incision and used to view the
      image on a monitor, while the second incision is employed for instrumentation. An
      examination with the patient under anesthesia should always be performed prior to
      the initiation of the procedure. The patient is positioned with the knee flexed
      and a lateral post secured to the side of the bed. Standard anteromedial and
      anterolateral portals are made, and an arthroscope is introduced through the
      anterolateral portal. Diagnostic arthroscopy is performed in a systematic
      fashion. Meniscal tears and other pathology are identified. With use of an
      arthroscopic probe, the features of the meniscal tear are determined.
      Arthroscopic punches and shavers are used to debride torn portions back to a
      stable rim. Knee arthroscopy is a highly effective procedure. Outcomes after
      partial medial meniscectomy are good to excellent in 80% to 100% of patients. A
      recent cost-effectiveness analysis demonstrated that knee arthroscopy is more
      cost-effective than coronary artery bypass surgery or total knee arthroplasty.

PMID- 30237916
TI  - Closed Cephalomedullary Nailing with Patient in Lateral Decubitus Position for
      Repair of Peritrochanteric Femoral Fracture.
AB  - Introduction: Closed repair of peritrochanteric fractures with cephalomedullary
      nail fixation with the patient in the lateral decubitus position on a flat table
      with manual traction may allow improved fracture reduction and fixation in
      comparison with what is possible in a supine setup. Indications &
      Contraindications:  Step 1 Operating Room Preparation: Perform sterile
      preparation, have the patient brought to the operating room, induce anesthesia,
      and place the patient in the lateral decubitus position before sterile draping.
      Step 2 Fracture Reduction: Reduce the fracture using manual traction and slight
      internal or external rotation; confirm anatomic reduction radiographically. Step
      3 Nail Insertion: Determine the appropriate nail length, identify the nail entry
      point, open the femoral canal, insert a ball-tipped guide into the canal, insert
      the nail, and attach the aiming arm to the nail. Step 4 Insertion of Cephalic Lag
      Screw: Attach the aiming arm to the insertion handle, pass a guidewire, drill
      over the guidewire to open the lateral cortex, and insert the cannulated screw
      with soft hammer blows. Step 5 Insertion of Distal Interlocking Screw: Confirm
      fracture reduction on anteroposterior and lateral views, drill through the
      lateral cortex of the femur for the distal interlocking screw, measure the screw
      length, insert the screw, and remove the aiming arm if one was used. Step 6 Final
      Radiographic Imaging: Obtain anteroposterior and lateral views to confirm
      maintenance of fracture reduction and appropriate placement and length of the
      nail and cephalic and distal locking screws. Step 7 Wound Closure: Irrigate and
      close the wounds, and apply operative dressings. Results: Intramedullary device
      technology has been altered to address the complication of periprosthetic
      fracture at the distal tip that made earlier intramedullary fixation less
      appealing compared with extramedullary fixation for stable fracture patterns.
      Pitfalls & Challenges: 

PMID- 30237918
TI  - A Novel Intramedullary Locked Fixation Device for Treatment of Clavicle Shaft
      Fractures.
AB  - Introduction: An intramedullary nail (the Sonoma CRx) with a unique flexible
      anatomical design and locking system is a viable alternative for treatment of
      displaced and shortened clavicle shaft fractures. Indications &
      Contraindications:  Step 1 Positioning: Place the patient in the beach-chair
      position and drape the arm free so that you can obtain an exaggerated
      anteroposterior and an axial fluoroscopic view of the clavicle by manipulating
      the position of the arm. Step 2 Skin Incision: The surgical technique
      necessitates opening the fracture site in order to implant the device. Step 3
      Preparing the Medial Fragment: The preparation of the medial fragment is of
      utmost importance as the intramedullary Sonoma CRx nail should be placed as far
      as possible into the medial fragment of the clavicle, to provide the highest
      level of stability and the lowest risk of device failure. Step 4 Preparing the
      Lateral Fragment: Preparation of the lateral fragment is more challenging than
      preparation of the medial fragment because of its relative immobility and shorter
      medullary canal. Step 5 Placement of the Intramedullary Nail: Use the longest
      possible intramedullary nail that the clavicle can accommodate and insert the
      nail as far medially as possible into the medullary canal of the clavicle bone.
      Step 6 Activation of the Locking Device: Lock the device at its medial end with
      distally deployed grippers and laterally with a locking screw placed through a
      jig. Step 7 Management of Comminuted Fracture Fragments: Comminuted fractures are
      not a contraindication to the use of the intramedullary device as they can be
      reduced by the nail and secured by using cerclage sutures. Step 8 Postoperative
      Management: Protect the affected shoulder in a shoulder immobilizer for six
      weeks. Results: In our original study, forty-seven consecutive patients with a
      displaced and shortened clavicle shaft fracture were treated with open reduction
      and internal fixation using the Sonoma CRx device. Pitfalls & Challenges: 

PMID- 30237919
TI  - Placement of Thoracic Pedicle Screws.
AB  - Thoracic pedicle screws have become the spinal anchor of choice because of the
      superior biomechanics of this technique. It is widely used for the treatment of
      scoliosis, spinal deformity (such as kyphosis), trauma, tumors, infection, and
      other pathologies. The technique demands precision as malposition can result in
      spinal cord or visceral injury with potential catastrophic consequences (death or
      paralysis). There have been many published articles looking at the anatomy and
      the anatomic variation in various populations according to race, age, deformity,
      etc. Lenke and others have developed start point guidelines that seem to have
      reasonable validity. There are two basic screw trajectories:The straightforward
      technique.The anatomic trajectory. The straightforward technique parallels the
      superior end plate of the instrumented vertebra. It has the best insertional
      torque. The anatomic trajectory bisects the sagittal axis of the pedicle,
      typically 15 degrees  cranial to caudal, and has the largest available bone
      channel. The accuracy of placement is a debated topic. There are several meta
      analyses and systematic reviews that address this question. However, there are a
      variety of definitions of acceptable compared with optimal placement. The current
      gold standard for judging screw placement is the use of computed tomography;
      however, it carries a substantial radiation burden to the patient, which must be
      considered. There are a myriad of described techniques, including freehand
      (anatomically based), fluoroscopy-guided, and three-dimensional (3-D) image
      guided methods. All have their advantages and disadvantages. Surgeons must find
      the technique that is safe and reliable in their hands. The procedure is
      performed with the following steps:Preoperative planning is done by initially
      looking at plain radiographs and by assessing bending radiographs and
      preoperative computed tomography scans, if available.The patient is placed on a
      Jackson table, which is radiolucent and allows easy access for C-arm or O-arm
      technology.Locate the start point around the thoracic level (T12, T8, etc.); a
      review of the Lenke start point map is helpful.Create the dorsal cortical hole,
      which is best done with a small pilot hole; we recommend the use of a 3-mm high
      speed burr (Midas Rex; Medtronic).Create a track within the pedicle by probing
      with either a navigated probe or a Lenke-style freehand probe.Confirm the
      accuracy of the screw tract placement, which can be done by palpation although it
      is not 100% reliable.Place the screw after tapping 1 mm less than the nominal
      screw diameter.Confirm the accuracy of screw placement with fluoroscopy or plain
      radiographs; 3-D intraoperative imaging is the most reliable technique, but it
      also exposes the patient to the most radiation.Confirm the neurological status of
      the patient by monitoring the motor evoked potential signals after screw
      placement.Close the wound after the screws have been checked with intraoperative
      2-D or 3-D imaging to ensure that they have not cut or plowed out. The results of
      thoracic pedicle screw placement are specific to the spinal condition treated.
      For adolescent idiopathic scoliosis, no brace is needed and walking can be
      progressed as tolerated. With good thoracic screw placement, rehabilitation
      typically is accelerated because a stable spinal construct is achieved. Most
      patients are able to walk without any sort of external mobilization or special
      adjunctive protection.

PMID- 30237920
TI  - Sacral Alar Iliac Fixation for Spine Deformity.
AB  - Introduction: As the anatomy of the lumbosacral junction presents a unique
      challenge for the spine surgeon with regard to achieving a solid fusion, we
      describe the sacral alar iliac (SAI) technique, which can be used for the
      placement of pelvic anchors during posterior spinal arthrodesis. Indications &
      Contraindications:  Step 1 Patient Positioning: Position the patient prone on a
      radiolucent table. Step 2 Surgical Approach: In approaching the starting point,
      perform limited dissection of the soft tissue between the S1 and S2 dorsal
      foramina, while taking care to minimize unnecessary dissection and blood loss.
      Step 3 Channel Creation: As the ideal screw pathway is one-third in the sacral
      ala and two-thirds in the ilium, start at the junction between the 1st and 2nd
      sacral segments, cross the sacroiliac joint, travel caudally toward the sciatic
      notch, cross between the inner and outer table of the ilium, and end close to the
      anterior inferior iliac spine cranial to the acetabular roof (Figs. 5-A and 5-B).
      Step 4 Screw Placement: In most children and adults, use screws with an outer
      diameter >=9 mm, which are recommended to prevent screw breakage. Step 5 Rod
      Placement: Ensure that the SAI screws are in line with the remainder of the
      spinal anchors to allow for ease of rod insertion. Step 6 Wound Closure: Perform
      carefully layered wound closure per routine at the end of the case, with special
      attention to meticulous hemostasis. Results: In a review of the cases of 32
      pediatric patients treated with SAI fixation, Sponseller et al.27 reported a mean
      pelvic obliquity correction of 70% and a mean major coronal Cobb angle correction
      of 67%. Pitfalls & Challenges: 

PMID- 30237921
TI  - Percutaneous in Situ Fixation of Slipped Capital Femoral Epiphysis.
AB  - Slipped capital femoral epiphysis (SCFE), a common cause of adolescent hip pain,
      is a displacement of the femoral head through the proximal femoral physis. The
      exact etiology of SCFE is unknown, but both biochemical and biomechanical
      factors, including obesity, femoral retroversion, increased physeal obliquity,
      puberty, and endocrinopathies, play a role. Patients often present with hip,
      groin, or knee pain and an antalgic gait. On physical examination, obligate
      external rotation of the lower limb with passive hip flexion is a hallmark of
      SCFE. The diagnosis is confirmed with radiographs, with advanced imaging reserved
      for atypical presentations. Any degree of SCFE is an indication for internal
      stabilization. Percutaneous in situ fixation remains the gold-standard treatment
      for slipped capital femoral epiphysis. The procedure is performed with the
      following steps: (1) the patient is positioned supine on a fracture table with
      the contralateral lower limb in the hemilithotomy position; (2) a 1-cm
      longitudinal incision is made over the anterolateral aspect of the proximal part
      of the femur; (3) under fluoroscopic guidance, a guidewire is advanced freehand
      into the "center-center" of the epiphysis, stopping approximately 3 mm short of
      the articular surface; (4) the guidewire is overdrilled, and a 6.5-mm partially
      threaded cannulated screw of appropriate length is inserted into the epiphysis;
      (5) the proximal part of the femur is brought through a full range of internal
      external rotation under fluoroscopy to confirm that the screw has not violated
      the joint cavity; and (6) the wound is closed in layers and a sterile dressing is
      applied. Postoperatively, the patient's weight-bearing status is advanced on the
      basis of the stability of the SCFE. Radiographic follow-up is performed at six
      month intervals to monitor the contralateral hip until skeletal maturity.
      Treatment outcomes and complications such as osteonecrosis and chondrolysis
      correlate with the severity and stability of the slip on presentation. Long-term
      follow-up has shown good-to-excellent outcomes after in situ screw fixation of
      stable slips.

PMID- 30237922
TI  - Isolated Subtalar Arthrodesis.
AB  - Introduction: An isolated subtalar arthrodesis through a sinus tarsi approach
      with cannulated screw fixation is safe, reproducible, and effective for specific
      hindfoot pathology in adults. Indications & Contraindications:  Step 1
      Preoperative Planning: Perform a comprehensive clinical and radiographic
      assessment. Step 2 Patient Positioning: Position the patient supine on the
      operating table with a bump under the ipsilateral hip, to internally rotate the
      involved leg. Step 3 Incision: Mark a longitudinal incision from just inferior to
      the tip of the lateral malleolus and extending toward the base of the 4th
      metatarsal. Step 4 Approach: Expose the subtalar joint by reflecting the extensor
      digitorum brevis and protecting the peroneal tendons. Step 5 Joint Preparation:
      Meticulously prepare the subtalar joint using osteotomes and curets down to
      healthy bleeding subchondral bone. Step 6 Reduction and Fixation: Reduce the
      subtalar joint into 5 degrees  of valgus and fix it with cannulated screws. Step
      7 Wound Closure: Meticulously close the wound in layers and place the lower leg
      in a well-padded plaster back slab with the ankle in a neutral position. Step 8
      Postoperative Care: The operatively treated leg is kept immobilized and non
      weight-bearing for the first 6 weeks. Results: Numerous retrospective articles
      have reported high fusion rates and good functional outcomes after isolated
      subtalar arthrodesis, for all indications. Pitfalls & Challenges: 

PMID- 30237923
TI  - Arthroscopic Subacromial Decompression and Acromioplasty.
AB  - Arthroscopic subacromial decompression with acromioplasty is among the most
      commonly performed arthroscopic shoulder procedures and is an important aspect of
      any orthopaedic surgeon's armamentarium. This procedure is indicated for
      refractory subacromial bursitis and subacromial impingement. It is also a routine
      portion of rotator cuff repair exposure. The procedure aims to remove the
      subacromial bursa, which can serve as a pain generator, as well as any
      osteophytes on the undersurface of the acromion, which can lead to impingement
      and, in some circumstances, bursal-sided rotator cuff tears. Multiple randomized
      clinical trials have demonstrated no benefit for this procedure as an initial
      treatment in patients with subacromial bursitis2,7,8, and thus this procedure is
      indicated only for patients with refractory subacromial bursitis. The steps of
      this procedure include (1) placement of the arthroscope in the subacromial space
      and establishment of a lateral working portal, (2) performance of a thorough
      subacromial bursectomy, (3) achievement of hemostasis and subperiosteal exposure
      of the undersurface of the acromion, and (4) smoothing of the undersurface of the
      acromion and removal of any anterolateral osteophytes. Outcomes after this
      procedure have shown significant increases in UCLA (University of California at
      Los Angeles), Constant, visual analog pain scale, and Simple Shoulder Test scores
      over the preoperative status2,5,10,11. Complications, while infrequent, are
      mostly related to overresection or underresection of the acromion.

PMID- 30237924
TI  - Two-Stage Surgical Treatment of Complex Femoral Deformities with Severe Coxa Vara
      in Polyostotic Fibrous Dysplasia.
AB  - Introduction: For complex femoral deformities in patients affected by polyostotic
      fibrous dysplasia and coxa vara associated with shepherd's crook deformity of the
      femoral shaft, the correct treatment is stabilization with an interlocking
      cervicodiaphyseal nail after correction of all of the femoral deformities.
      Indications & Contraindications:  Step 1 The First-Stage Procedure
      Intertrochanteric Valgus Osteotomy and Fixation with a Hip Blade-Plate
      Preoperative Planning: Evaluate the patient radiographically and select the
      hardware. Step 2 Patient Preparation: Position the patient on the traction table.
      Step 3 Preparation of the Lateral Aspect of the Proximal Part of the Femur and
      Marking the Position for Both the Osteotomy and the Hip Blade-Plate: Expose the
      lateral aspect of the proximal part of the femur and mark the position of both
      the blade-plate and the osteotomy. Step 4 Blade-Plate Positioning Osteotomy and
      Osteotomy Fixation: Prepare the slot for the blade, perform the osteotomy, and
      correct the valgus alignment of the proximal part of the femur. Step 5
      Postoperative Management: Check postoperative bleeding, provide blood
      transfusions if needed, and have the patient resume walking. Step 6 The Second
      Stage Procedure-Hip Plate Removal Osteotomy of the Femoral Shaft to Correct the
      Shepherd's Crook Deformity and Stabilization with a Cervicodiaphyseal Nail
      Preoperative Planning: Study the patient radiographically, simulate the
      osteotomies, perform another assessment of lower-limb length, and select the
      hardware. Step 7 Patient Preparation Plate Removal and Drilling of Kirschner
      Wires to Mark the Site of the Planned Osteotomies: Position the patient on the
      traction table and expose the lateral aspect of the femur from the tip of the
      greater trochanter to the level of the most distal planned osteotomy. Step 8
      Perform All of the Osteotomies and Drill a Medullary Canal in the Osteotomy
      Fragments: All of the osteotomies are performed, and a medullary canal is drilled
      in each femoral fragment. Step 9 Nail and Spiral Blade Insertion Stabilization of
      Osteotomies and Closure: Introduce the nail into the osteotomy fragments and
      insert the spiral blade and distal locking screws. Step 10 Postoperative
      Management: Check postoperative bleeding, which is usually marked; administer
      blood transfusions as needed; and have the patient resume walking. Results: We
      performed this surgery on 13 femora in 11 patients. Pitfalls & Challenges: 

PMID- 30237925
TI  - Percutaneous Screw Fixation of Lateral Condylar Humeral Fractures.
AB  - Lateral condylar humeral fractures are the second most common elbow injury in
      children and commonly occur between the ages of 5 and 10 years. There are several
      systems for classification of this fracture, including those of Milch (fracture
      line location) and Jakob et al. (displacement). Although nonoperative management
      is indicated for nondisplaced or minimally displaced fractures (<2 mm), operative
      fixation is indicated for greater displacement. Traditionally, open reduction and
      internal fixation has been the method used to ensure adequate reduction. However,
      closed reduction and internal fixation techniques for displaced fractures have
      been receiving increasing attention, with recent studies showing promising
      results. Several constructs (multiple smooth pins, a single lag screw, and
      threaded pins) for closed reduction and internal fixation have been described.
      Smooth-pin fixation has the advantage of a small diameter and easy removal,
      whereas threaded pins combine a small diameter with compressive properties.
      Compression of these small, articular fractures is important, and the optimal
      mode of fixation for maintaining fracture reduction is debated. Fixation with a
      partially threaded lag screw works by achieving metaphyseal compression,
      preventing loss of reduction of the distal fragment. In our experience, the
      compressive abilities of smooth and threaded pins are limited in the soft
      osteocartilaginous lateral condyle. Partially threaded lag screw fixation is
      indicated for pediatric patients with a substantially displaced (Jakob type-II or
      III) lateral condylar fracture. The major steps of the procedure are (1)
      preoperative planning with anteroposterior, lateral, and oblique radiographs; (2)
      supine positioning of the patient with the shoulder in abduction; (3) closed
      reduction with manual pressure; (4) guide-pin insertion through the lateral
      column of the distal part of the humerus; and (5) exchange of the guide pin with
      a lag screw. Postoperatively, the elbow is immobilized with a bivalved long-arm
      fiberglass cast or a posterior splint. The cast or splint is removed after
      interval healing is demonstrated on radiographs, and the lag screw is removed
      after complete fracture union is demonstrated. Complications are rare, and
      patients are expected to have decreased infection and open-reduction rates
      compared those treated with pin fixation.

PMID- 30237926
TI  - Surgical Reduction and Fixation of Tibial Spine Fractures in Children:
      Arthroscopic Suture Fixation.
AB  - The pediatric tibial spine fracture can be considered the equivalent of the
      pediatric anterior cruciate ligament (ACL) rupture, especially considering that
      failure to manage these injuries appropriately could result in substantial knee
      pathology and long-term functional failure. Arthroscopy-assisted internal
      fixation of the tibial spine fracture minimizes the patient's hospital stay
      compared with that associated with an open arthrotomy approach, but the
      postoperative rehabilitation may be paramount to a successful outcome. Compared
      with conservative management, surgical reduction and fixation of these fractures
      decreases the risks of comorbidities related to meniscal tissue entrapment, the
      risk of anterior impingement, and the need for revision treatment. Repair should
      be considered for fractures displaced >5 mm at their maximum, given the risk of
      revision when these cases are treated without surgery. After reduction and
      tentative fixation, the fracture can be managed with either suture or screw
      fixation. For suture fixation, the surgical steps include (1) creation of
      peripatellar arthroscopy portals; (2) evacuation of the hematoma and clearing of
      the fracture bed of meniscus and callus; (3) reduction, with particular attention
      paid to articular surface extension if present, and tentative fixation with an
      ACL tibial guide and placement of threaded Kirschner wire; (4) drilling of bone
      tunnels for suture passage using the tibial guide juxtaposed to the ACL insertion
      (both medially and laterally, in turn); (5) passing a suture of choice
      (nonabsorbable type requiring intraoperative fluoroscopy to evaluate tunnel
      placement during the previous step); (6) passage of suture both posterior and
      anterior to the ACL fibers; (7) removal of the tentative threaded Kirschner wire;
      (8) tying of the posterior suture over a bone bridge; (9) tying of the anterior
      suture over the same bone bridge; and (10) standard arthroscopy portal closure
      and placement of dressings including immobilization of the knee. For screw
      fixation, the surgical steps are slightly different, with Step 3 followed by (4)
      placement of the guidewire (if a cannulated screw is being used), (5)
      intraoperative assessment of the fracture reduction and drilling of the screw
      track perpendicular to the vector of the ACL pull and tentative threaded
      Kirschner wire fixation, (6) measurement and placement of the final screw
      implant, (7) removal of the tentative Kirschner wire fixation prior to final
      setting of the screw, and (8) standard arthroscopy portal closure and placement
      of dressings including immobilization of the knee. Radiographic and functional
      outcomes are excellent with either fixation technique in this pediatric
      population.

PMID- 30237927
TI  - Surgical Reduction and Fixation of Tibial Spine Fractures in Children: Multiple
      Fixation Strategies.
AB  - A tibial spine fracture is an osseous avulsion of the anterior cruciate ligament
      (ACL) from its attachment on the intercondylar tibial eminence. Most commonly
      affecting the immature skeletal systems of children between 8 and 14 years old,
      tibial spine fractures are frequently regarded as the pediatric equivalent to
      adult midsubstance ACL injuries. While all nondisplaced and selected partially
      displaced fractures can be treated nonoperatively, surgical fixation is most
      frequently used for completely displaced tibial spine fractures. The goals of
      surgery include osseous union, restoration of knee stability, return to function,
      treatment of associated injuries, and restoration of the range of motion. Current
      evidence has demonstrated equivalent outcomes for open and arthroscopic reduction
      strategies, as well as for screw-based and suture-based fixation techniques. The
      surgeon should be prepared to offer a multitude of fixation techniques based on
      intraoperative findings that will provide stable anatomic reduction, including,
      for instance, the use of suture-based fixation in comminuted fragments. This
      video article demonstrates an arthroscopic procedure to repair a tibial spine
      fracture, including 3 methods of fixation, in the following major steps: (1)
      preoperative planning, (2) patient positioning and surgical exposure, (3)
      evacuation of the hemarthrosis, (4) diagnostic arthroscopy, (5) preparation of
      the fracture fragment, (6) reduction of the fracture fragment, (7) fixation
      option 1: screw fixation, (8) fixation option 2: suture anchor, (9) fixation
      option 3: suture, and (10) dynamic assessment of stability and closure. Excellent
      functional outcomes using this procedure have been documented and, with
      appropriate postoperative care that includes range-of-motion exercises beginning
      as early as 1 to 2 weeks postoperatively, patients are expected to recover
      function and to resume a normal activity level. Complications, including
      nonunion, malunion, and arthrofibrosis, can be reduced when patients with
      completely displaced tibial spine fractures are treated with surgical management.

PMID- 30237928
TI  - Tibial Spine Fractures in Children: Variations on Treatment for an ACL Injury
      Variant.

PMID- 30237929
TI  - Lengthening of the Femur with a Remote-Controlled Magnetic Intramedullary Nail:
      Retrograde Technique.
AB  - Introduction: Femoral lengthening with an intramedullary nail inserted through a
      retrograde approach offers the unique benefit of accurate deformity correction
      and distraction osteogenesis without the need for external fixation with its
      inherent challenges. Indications & Contraindications:  Step 1 Planning the
      Deformity Correction and Nail Insertion: The key to a successful deformity
      correction and proper nail placement is preoperative planning. Step 2 Insert the
      Rotation Marker Pins and Blocking Screws: Insert 2 Steinmann pins or half-pins
      into the proximal and distal aspects of the femur to mark any rotational
      deformity that is being corrected or to ensure that no rotational deformity is
      created. The Steinmann pins need to be >=3 mm in diameter to prevent bending with
      loss of rotational reference. We prefer 5-mm or 6-mm Schanz pins for this role.
      These sturdy pins may be used as a "joystick" for manipulating the distal
      fragment to achieve a correction. Step 3 Prepare the Distal Fragment: This step
      includes the approach to and reaming of the distal fragment, which is critical to
      the limb alignment. Step 4 Osteotomy: Perform the percutaneous osteotomy, which
      allows for correction of the deformity, prior to reaming the proximal segment.
      Step 5 Prepare the Proximal Fragment: While holding the distal fragment in the
      reduced position, prepare the proximal fragment for nail insertion. Step 6 Nail
      Insertion: Insert the nail in a standard fashion, avoiding excessive force that
      could damage it or jam it into the proximal fragment. Step 7 Lock the Nail: Lock
      the nail from the distal or proximal end first. The femoral distractor helps to
      keep the rotation accurate during locking and helps to serve as a handle to
      obtain perfect overlapping circles of the locking screw site on fluoroscopy.
      However, the external fixator may be obstructive for distal locking in
      particular. The fixator can be removed for distal locking and reattached for
      proximal locking. Step 8 Final Blocking Screws: Check the anteroposterior and
      lateral fluoroscopic images and decide how stable the nail is in the bone. Will
      the fragment shift into varus, valgus, or flexion? Step 9 Mark the Magnet and
      Test the Nail: Mark the position and orientation of the magnet in the nail on the
      patient's skin to indicate where to place the external magnet for lengthening.
      Step 10 Postoperative Care and Lengthening: Postoperative management involves
      nail distraction, venous thromboembolic (VTE) prophylaxis, and adherence to a
      specific weight-bearing protocol. Results: Femoral lengthening with the remote
      controlled magnetic intramedullary nail has had excellent clinical efficacy3.
      Pitfalls & Challenges: 

PMID- 30237930
TI  - Intramedullary Pinning for Displaced Fifth Metacarpal Neck Fractures: Closed
      Reduction and Fixation Using Either an Open Antegrade or Percutaneous Retrograde
      Technique.
AB  - Introduction: Although the majority of fifth metacarpal neck fractures can be
      treated nonoperatively, surgery may be indicated when there is severe shortening
      or angulation of the metacarpal bone1. Indications & Contraindications:  Step 1
      Antegrade Intramedullary Pinning Operating-Room Setup and Making the Incision:
      Proper positioning of the image intensifier and the treating surgeons is
      important. Step 2 Antegrade Intramedullary Pinning Bend the Kirschner Wires:
      Prepare and bend the Kirschner wires before insertion. Step 3 Antegrade
      Intramedullary Pinning Make a Hole in the Fifth Metacarpal Base: Create a hole
      for Kirschner wire insertion in the center of the fifth metacarpal base. Step 4
      Antegrade Intramedullary Pinning Insert Kirschner Wires and Close the Wound:
      Insert the Kirschner wires through the hole of the fifth metacarpal base. Step 5
      Antegrade Intramedullary Pinning Postoperative Care: An additional skin incision
      is necessary to remove the Kirschner wires after bone union. Step 1 Percutaneous
      Retrograde Intramedullary Pinning Operating-Room Setup: Proper positioning of the
      image intensifier and treating surgeon is important. Step 2 Percutaneous
      Retrograde Intramedullary Pinning Fracture Reduction: Reduce the fifth metacarpal
      neck fracture using the Jahss maneuver. Step 3 Percutaneous Retrograde
      Intramedullary Pinning Insert Kirschner Wires: Fix the reduced metacarpal neck
      fracture using 2 Kirschner wires placed percutaneously in a retrograde direction,
      with the second wire inserted after the first wire passes the fracture site but
      before it passes the metacarpal base. Step 4 Percutaneous Retrograde
      Intramedullary Pinning Kirschner Wire Management: The proximal end of the
      Kirschner wire penetrating outside the dorsal skin of the wrist enables the
      surgeon to percutaneously retrieve the Kirschner wire after fracture union. Step
      5 Percutaneous Retrograde Intramedullary Pinning Postoperative Care: The
      percutaneous Kirschner wire is retrieved. Results: In a previous prospective
      randomized analysis of patients treated with antegrade intramedullary pinning and
      percutaneous retrograde intramedullary pinning for displaced fifth metacarpal
      neck fracture1, we found that the flexion arc of the MCP joint, visual analog
      pain scale score, grip strength, and DASH (Disabilities of the Arm, Shoulder and
      Hand) score4 were significantly better in the antegrade intramedullary pinning
      group at 3 months postoperatively. Pitfalls & Challenges: 

PMID- 30237931
TI  - Transforaminal Lumbar Interbody Fusion (TLIF).
AB  - Historically, posterior lumbar interbody fusion was performed using a directly
      posterior procedure (PLIF). Transforaminal lumbar interbody fusion (TLIF)
      utilizes a more lateral window in order to access the interbody space without
      excessive dural retraction. Theoretical advantages of TLIF include increased
      fusion success, more complete foraminal decompression, better correction of
      deformity, and more effective treatment of discogenic pain. The procedure is done
      with the following steps:1 and 2. Preoperative planning and patient positioning
      are important to maximize the efficiency of the procedure. There is a wide
      variety of instrumentation and technique options; therefore, a systematic
      approach starting with setup is important.3. The spine is approached through a
      standard posterior midline incision. It is not necessary to expose the lateral
      gutters, but the addition of posterolateral fusion is common.4. Pedicle screw
      placement is undertaken via a standard approach.5. Decompression is initiated
      with a laminectomy in the midline, exposing the ligamentum.6. The ligamentum is
      carefully removed, and hemostasis is obtained. A facetectomy is then performed.7.
      Once the posterior bone elements are resected and the decompression is complete,
      the dura and neural elements are mobilized. The goal is to be able to access the
      posterior anulus and disc space easily without any dural tension.8. Distraction
      through the TLIF level helps facilitate interbody placement. We describe a triple
      distraction technique that uses the midline elements, and both contralateral and
      ipsilateral distraction methods.9. A window is formed on the disc, with care
      taken to protect the exiting and traversing roots. The window is enlarged using a
      combination of box osteotomes and Kerrison rongeurs. A window that is a minimum
      of 10 mm in size facilitates disc space preparation.10 and 11. Disc space
      preparation is performed using a combination of curets, pituitary rongeurs, and
      end-plate preparation tools. Thorough disc-space preparation is critical for both
      correcting the deformity and obtaining a solid fusion.12. The disc space is sized
      for an appropriate interbody cage. The anterior aspect of the disc space and the
      cage are both packed with bone graft. This may involve the use of iliac crest
      graft, local bone, or bone substitutes, depending on the specific clinical
      situation.13. Cage and screw placement is verified by biplane radiography, and
      lordosis is restored by compression across the screws bilaterally. Osteotomy of
      the contralateral facet may be necessary to achieve substantial restoration of
      lordosis.14. If the lateral gutters have been exposed, grafting in this region is
      undertaken as well. Care must be taken with graft placement on the TLIF side as
      facet and pars resection leaves the exiting route exposed.15. Closure is
      undertaken in a standard fashion.Postoperative recovery does not differ
      substantially from other standard fusion procedures. Mobilization is undertaken
      over the first several weeks, and fusion healing is expected in the 6-month to 1
      year time frame.

PMID- 30237932
TI  - Minimally Invasive Cervical Foraminotomy.
AB  - Introduction: The minimally invasive posterior cervical foraminotomy, a motion
      preserving procedure, is an excellent treatment for patients with unilateral
      radiculopathy secondary to a laterally located herniated disc or foraminal
      stenosis. Indications & Contraindications:  Step 1 Position the Patient Video 1:
      Place the patient in a prone position on a Jackson table with 6 posts and with
      the head resting comfortably on a soft facial pillow, and tape the shoulders down
      to provide traction to the skin and help with fluoroscopic visualization of the
      lower cervical levels. Step 2 Perform the Skin Incision: Make the skin incision
      adjacent to the spinous process on the side of the abnormality over the operative
      level. Step 3 Use Tubular Dilators to Make a Working Portal: Use sequential
      dilators to create a working portal and secure the working tube overlying the
      lamina-facet junction of the operative level. Step 4 Perform the
      Laminoforaminotomy Video 2: Perform the laminoforaminotomy with the use of a high
      speed drill and a Kerrison rongeur to create a working window into the foramen.
      Step 5 Perform the Foraminal Decompression Video 3: Use a nerve hook to
      superiorly retract the nerve root, and perform a discectomy and decompression.
      Step 6 Wound Closure and Postoperative Care: Obtain hemostasis with
      electrocautery or hemostatic foam and close the wound with a standard layered
      closure. Results: A systematic review and meta-analysis of studies on open or
      minimally invasive surgical (MIS) techniques for posterior cervical foraminotomy
      showed a pooled clinical success rate of 92.7% for the 509 patients managed with
      the open technique and 94.9% for the 208 patients who had the MIS technique; the
      difference was not significant (p = 0.418)2. Pitfalls & Challenges: 

PMID- 30237933
TI  - Autologous Chondrocyte Implantation.
AB  - Introduction: Autologous chondrocyte implantation (ACI) for the treatment of
      articular cartilage lesions of the knee joint provides successful and durable
      long-term outcomes. Indications & Contraindications:  Step 1 Preoperative
      Planning Video 1: Obtain standing radiographs and magnetic resonance imaging
      (MRI) scans to identify all associated abnormalities (background factors). Step 2
      Arthroscopic Assessment and Cartilage Biopsy Video 2: Evaluate the knee joint
      systematically and harvest cartilage tissue from the non-weight-bearing area.
      Step 3 Make the Incision for the Arthrotomy Video 3: Use a medial or lateral
      parapatellar arthrotomy and expose the lesion adequately. Step 4 Prepare the
      Defect Video 4: Debride all fissured and unstable articular cartilage surrounding
      the full-thickness chondral injury down to healthy contained cartilage. Step 5
      Address Associated Abnormalities: Address associated abnormalities (predisposing
      background factors) to optimize recovery and a successful outcome. Step 6 Prepare
      and Fix the Collagen Membranes Video 5: Orient the membrane patch with the rough
      surface to the subchondral bone and the smooth surface toward the articular
      surface; then sew it, tying the sutures knots on the membrane and not the
      cartilage, to tension it adequately throughout the entire defect. Step 7
      Chondrocyte Implantation Video 6: Gently deliver the cells and fill the defect.
      Step 8 Postoperative Care: (1) Initiate range-of-motion exercises to enhance
      chondrocyte regeneration and decrease the likelihood of intra-articular adhesion,
      (2) protect the graft from loading for 6 to 12 weeks after surgery to prevent
      graft overload and central degeneration or delamination of the graft, and (3)
      initiate isometric muscle exercises to regain muscle tone and prevent atrophy.
      Results: ACI provided durable outcomes in 210 patients followed prospectively for
      10 to 17 years after treatment with the first-generation ACI-periosteum
      technique6. Pitfalls & Challenges: 

PMID- 30237934
TI  - What's the Risk? Older Women Report Fewer Symptoms for Suspected Acute Coronary
      Syndrome than Younger Women.
AB  - The purpose of the study was to determine whether older (>=65 years) and younger
      (<65 years) women presenting to the emergency department (ED) with symptoms
      suggestive of acute coronary syndrome (ACS) varied on risk factors, comorbid
      conditions, functional status, and symptoms that have implications for emergent
      cardiac care. Women admitted to five EDs were enrolled. The ACS Symptom Checklist
      was used to measure symptoms. Comorbid conditions and functional status were
      measured with the Charlson Comorbidity Index and Duke Activity Status Index.
      Logistic regression models were used to evaluate symptom differences in older and
      younger women adjusting for ACS diagnosis, functional status, body mass index
      (BMI), and comorbid conditions. Analyses were stratified by age, and interaction
      of symptom by age was tested. Four hundred women were enrolled. Mean age was 61.3
      years (range 21-98). Older women (n = 163) were more likely to have hypertension,
      hypercholesterolemia, never smoked, lower BMI, more comorbid conditions, and
      lower functional status. Younger women (n = 237) were more likely to be members
      of minority groups, be college-educated, and have a non-ACS discharge diagnosis.
      Younger women had higher odds of experiencing chest discomfort, chest pain, chest
      pressure, shortness of breath, nausea, sweating, and palpitations. Lack of chest
      symptoms and shortness of breath (key symptoms triggering a decision to seek
      emergency care) may cause older women to delay seeking treatment, placing them at
      risk for poorer outcomes. Younger African American women may require more
      comprehensive risk reduction strategies and symptom management.

PMID- 30237935
TI  - Outcome Measures in Chronic Rhinosinusitis.
AB  - Purpose of Review: Chronic rhinosinusitis (CRS) has a significant impact on the
      quality of life of patients and is a high cost burden to both society and
      patients. There is a variety of objective and subjective outcome measures that
      exist to assess the effectiveness of interventions. We aim to review current
      outcome measures available. Recent Findings: Traditionally, results have focused
      on objective measures, however, subjective outcome measures are gaining traction
      as being more important. Outcome measures in chronic rhinosinusitis are currently
      heterogeneous, thus limiting the impact of meta-analysis of past trial results.
      The development of a core outcome set may standardize the reporting of outcomes
      in chronic rhinosinusitis. Summary: We outline the outcome measures currently
      available and discuss a proposed core outcome set that may facilitate further
      value of research on interventions for CRS in adults.

PMID- 30237936
TI  - Correction: Complete mitochondrial genome sequence of the "copper moss"
      Mielichhoferia elongata reveals independent nad7 gene functionality loss.
AB  - [This corrects the article DOI: 10.7717/peerj.4350.].

PMID- 30237938
TI  - Comparison of Endoscopic Variceal Ligation with Endoscopic Sclerotherapy for
      Secondary Prophylaxis of Variceal Hemorrhage: A Randomized Trial.
AB  - Background Though endoscopic variceal ligation (EVL) is commonly being used and
      has overcome the disadvantages of sclerotherapy (ST), still sclerotherapy is used
      as a therapeutic procedure for bleeding esophageal varices in the present
      institute. Hence, the study was done to see the advantages of EVL over ST.
      Methods Patients with portal hypertension and bleeding esophageal varices
      underwent banding if found to have grade 3 or 4 varices. They were randomized to
      EVL group, where they were reviewed after two weeks for any residual varices for
      which repeat banding was done and endoscopic sclerotherapy (EST) group, where ST
      was done until the varices were obliterated or reduced to grade 1. The efficacy,
      complications, recurrent bleeding rate and recurrence of varices were compared.
      Results A total of 60 patients were included, 30 in each group. In EVL group,
      four sessions were needed to eradicate the varices in 73% of patients while it
      was five sessions in EST group (46% patients) (p-value = 0.0001). The mean number
      of sessions needed in EVL and EST group was 3.73 and 5.36, respectively. The
      average time taken for eradication of varices was 78.6 and 134.6 days in EVL and
      EST group, respectively (p-value = 0.004). Complications were higher in EST group
      (p-value < 0.05). Conclusion EVL alone was effective than ST in terms of the
      number of sessions needed for eradication of varices and total duration required
      to completely obliterate them. The complications were less in EVL group with no
      significant difference in recurrent bleeding rate and recurrence of varices
      between the groups.

PMID- 30237937
TI  - Sleep and Exercise in Emergency Medicine Residents: An Observational Pilot Study
      Exploring the Utility of Wearable Activity Monitors for Monitoring Wellness.
AB  - Introduction Burnout is well-documented in residents and emergency physicians.
      Wellness initiatives are becoming increasingly prevalent, but there is a lack of
      data supporting their efficacy. In some populations, a relationship between
      sleep, exercise, and wellness has been documented; however, this relationship has
      not been established in emergency medicine (EM) residents or physicians. We aim
      to determine whether a wearable activity monitor is a feasible method of
      evaluating exercise and sleep quality and quantity in emergency medicine
      residents and if these assessments are associated with greater perceived
      wellness. Methods Twenty EM residents from two training sites wore a wearable
      activity monitor (Fitbit ChargeTM, Fitbit, Inc., San Francisco, CA, USA) during a
      four-week EM rotation. The Fitbit recorded data on sleep quantity (minutes
      sleeping) and quality (sleep disruptions), as well as exercise quantity and
      quality (daily step count, daily active minutes performing activity of 3 - 6, and
      > 6 metabolic equivalents). Participants completed an end-of-rotation Perceived
      Wellness Survey (PWS), which provided information on six domains of personal
      wellness (psychological, emotional, social, physical, spiritual, and
      intellectual). PWS levels were compared between groups of subjects with higher or
      lower levels of activity and sleep (i.e., above and below the median subject
      averaged values) using the Mann-Whitney U test. Other subject characteristics
      were similarly assessed for their association with PWS. When a possible
      confounding effect was seen, the data was stratified and reviewed using a
      scatterplot. Results Of the 28 eligible residents, 23 agreed to participate. Of
      these, 20 and 16 wore the device for at least 50% of the respective days and
      nights during the observation period. Two devices were lost. One PWS was not
      completed. There was no statistically significant correlation between resident
      perceived wellness survey scores, sleep interruptions, average daily sleep
      minutes, daily step count, or average daily active minutes for the sample
      overall. However, first-year residents and residents from years two to five
      reported different median PWS scores of 13.9 and 17.1, respectively. Further
      exploration by the training group suggested that step counts may correlate with
      wellness in participants in their first year of residency, while the quantity of
      sleep may have an association with wellness in participants in years two through
      five of their residency. Conclusion Using wearable activity monitor devices to
      capture sleep and exercise data among residents does not seem to be an effective
      approach. Our data does not support our hypothesis that overall resident wellness
      was associated with exercise and sleep quality and quantity as measured by such a
      device. These results are counterintuitive and may be complicated by several
      measurement-related limitations and the possibility that benefits depend on the
      stage of training.

PMID- 30237939
TI  - Malignant Hypertension in Association with Low Estrogen Dose Oral Contraceptives:
      Case Report and Review of Literature.
AB  - Malignant hypertension (MH) has been described in association with high-dose (50 
      100 mcg) estrogen oral contraceptive pills (OCPs). Although the rise in blood
      pressure (BP) is usually mild, some women will have a more significant increase
      in BP, and hypertensive emergencies may very rarely occur. We present a 21-year
      old Caucasian female with a past medical history of fibromyalgia and family
      history of hypertension (both grandparents) who was admitted with a three-day
      history of headache and blurring of vision in her left eye with a BP of 210/150.
      Her medications, which were continued on admission, included tramadol, 100 mg
      twice daily (bid), and low-dose estrogen OCP. During the hospital course, she
      received different antihypertensive medications and her hypertension was
      controlled. A diagnosis of MH due to OCP was made. All antihypertensive
      medications were stopped, except metoprolol, and the patient was discharged home
      on metoprolol with a BP of 107/55 mmHg. On follow-up in the medical clinic three
      months later, her visual disturbances had completely resolved and her BP was
      98/56 mmHg.  One-third of patients aged 15 - 44 years old who develop MH are
      likely to be on high-dose estrogen OCP. As far as we know, our case is the third
      documented case of MH occurring in patients on low-dose estrogen OCP. Chronic use
      of oral contraceptives will slightly increase the systemic BP in most women. It
      is advisable to avoid OCP in high-risk patients and do regular BP checks on
      patients on OCP. In patients presenting with hypertension or MH while on OCP, the
      OCP should be discontinued.

PMID- 30237940
TI  - Pleomorphic Dermal Sarcoma of the Scalp.
AB  - Pleomorphic dermal sarcoma (PDS) is a rare mesenchymal tissue tumor.
      Distinguishing PDS from similar conditions, such as atypical fibroxanthoma (AFX),
      its less aggressive tumor counterpart, is difficult, as they are clinically and
      histologically similar. We present a case of a 77-year-old man presenting with a
      large nodular scalp lesion of three weeks duration. Pathology revealed a 3.3 cm
      invasive pleomorphic dermal sarcoma. Surgical excision with 2 cm margins was
      performed with successful healing of the graft. This case highlights a rare case
      of a large pleomorphic dermal sarcoma and discusses the histological features and
      management of PDS.

PMID- 30237941
TI  - The Principles and Procedures of Ultrasound-guided Anesthesia Techniques.
AB  - For inexperienced users, training with phantoms is an important part of training.
      Inexperienced users can teach themselves to gain significant procedural skills.
      Participating in training courses or practising with experts can enhance the
      outcomes. Inexperienced users need to understand the indications, clinical
      pearls, and pitfalls of each procedure to avoid potential complications.
      Inexperienced users can also train and teach themselves to become proficient in
      ultrasound techniques.

PMID- 30237942
TI  - Desensitization of Brentuximab Vedotin in a Patient with Hodgkin Lymphoma.
AB  - Brentuximab vedotin is a monoclonal antibody that targets the CD30 antigen. It is
      indicated for the treatment of Hodgkin lymphoma. Hypersensitivity reactions have
      occurred during infusions of brentuximab vedotin, ranging from mild to severe. We
      report a case of a 46-year-old male with stage IV nodular sclerosis Hodgkin
      lymphoma who developed a hypersensitivity reaction to brentuximab vedotin. He
      experienced a generalized rash, facial swelling, and mild airway obstruction. In
      order to continue treatment with brentuximab vedotin, we implemented a
      desensitization protocol. He was premedicated and a 12-step process was performed
      in which brentuximab vedotin was titrated over three hours. The protocol was
      successful, allowing the patient to receive subsequent infusions without
      hypersensitivity reactions.

PMID- 30237943
TI  - Metastatic Thymic Carcinoma with Long Survival After Treatment with Sunitinib.
AB  - Thymic carcinomas are the most aggressive histological subtype of thymic tumors
      with limited data to guide correct management. No standard treatments are
      available for patients with advanced thymic carcinoma after progressing while on
      platinum-based chemotherapy. We present a case of a patient with metastatic
      thymic carcinoma with an unusual response and favorable evolution after receiving
      treatment with sunitinib, obtaining a progression-free survival of 23 months,
      much higher than reported to date. We review the literature on the efficacy of
      sunitinib in metastatic thymic carcinoma after progression to first-line
      treatment with platinum combinations.

PMID- 30237944
TI  - Prevalence of Back Pain in Secondary School Students in an Urban Population:
      Cross-sectional Study.
AB  - Introduction The prevalence of low back pain (LBP) among secondary school
      students is increasing. The magnitude of the problem is not well quantified.
      Evidence shows LBP in adolescents can be a significant risk factor for back pain
      in adulthood. The present study aimed to determine the lifetime prevalence of LBP
      among secondary school students from schools of an urban metropolitan city and
      the prevalence of LBP in the presence of associated factors. Methods This cross
      sectional analytical study was done using a validated semi-structured
      questionnaire (N = 555; response rate, 85.3%). Secondary school students between
      the age of 12 and 15 years from three randomly selected urban secondary schools
      of Mumbai, India were recruited for the study. Results We analyzed the data for
      prevalence and odds ratios (OR), and we conducted a univariate analysis to
      determine the significance of LBP prevalence. We found the lifetime prevalence of
      LBP was high (32.9%). The prevalence of LBP was highly significant (p < .0001)
      among girls (confidence interval [CI]: 1.5 to 3.2; OR: 2.2), those who felt their
      school satchel was heavy (CI: 1.7 to 3.5; OR: 2.4) and those who watched
      television (TV; CI: 0.03 to 0.28; OR: 0.09). Conclusion We noted a high
      prevalence of LBP among adolescents. LBP had a significantly high prevalence
      among girls and in the presence of factors like a heavy school satchel and
      watching TV. LBP in adolescence is a significant risk factor in developing back
      pain in adulthood, and our findings highlight the need for awareness of LBP among
      stakeholders like educationists, policymakers, medical professionals and parents
      given the possible detrimental effects on adolescent children.

PMID- 30237945
TI  - Neurosyphilis: A Simulation Case for Emergency Medicine Residents.
AB  - Neurosyphilis is a dangerous and increasingly more prevalent sexually transmitted
      infection of the central nervous system caused by the bacterium Treponemapallidum
      that can present during the advanced stages of the disease (tertiary syphilis).
      Health care providers must remain vigilant in screening for syphilis in patients
      with high-risk behaviors as a delay in diagnosis and treatment may lead to
      symptom progression and debilitating sequelae years later. To date, there have
      been no published simulation case studies on neurosyphilis. This simulation case,
      based on a real patient encounter, is written for emergency medicine residents to
      diagnose and manage a patient presenting with the sequelae of neurosyphilis. This
      case was run for four separate iterations at a simulation center with two
      residents and an attending physician acting as confederates. Following the case,
      learners were provided with bedside debriefing, and a question and answer
      session. Based on post-simulation qualitative assessment, junior residents alone
      were less likely to perform a comprehensive integumentary exam without the
      presence of senior residents, although both groups failed to elicit pertinent
      sexual history until they discovered syphilitic lesions. After case completion
      and debriefing, all learners were able to demonstrate the understanding of the
      primary learning objectives.

PMID- 30237946
TI  - What Is the Optimal Radiation Technique for Esophageal Cancer? A Dosimetric
      Comparison of Four Techniques.
AB  - Background Esophageal cancer treatment requires large radiation fields due to the
      deep location of the esophagus in the mediastinum and the high incidence of
      radial spread. There is no optimal radiation technique to ensure appropriate
      target coverage and minimal dose to all normal structures. Methods Fifteen
      consecutive cases of locally advanced esophageal cancer treated with radical
      chemoradiation (CRT) were analyzed. The total prescribed dose was 50.4 Gy in 28
      fractions. A total of 60 plans were generated for analysis, including four
      different methods for each case. Method 1 consisted of a four-field conformal
      technique; method 2 was a two-plan technique (antero-posterior (AP), postero
      anterior (PA), two posterior oblique fields (RPO and LPO)); method 3 was a three
      field conformal technique (AP, LPO, RPO); and method 4 was a volumetric modulated
      arc radiotherapy (VMAT) technique. Dose ratios were calculated using the minimum,
      maximum, mean, and median doses of methods 2-4 over the dose of method 1. Ratios
      for the planning target volume (PTV) and to surrounding organs were analyzed.
      Results The mean PTV dose ratio ranged from 0.994 to 1.048 (SD = 0.01)
      representing an adequate target coverage for all techniques based on an analysis
      of variance (ANOVA). For the lungs, method 2 had the lowest lung V20 with a ratio
      of 0.861 (SD = 0.12), whereas method 3 had the highest with 1.644 (SD = 0.14).
      For the heart, method 3 had the lowest heart V40 with a mean dose ratio of 0.807
      (SD = 0.09), whereas method 2 had the highest with 1.160 (SD = 0.11). For the
      liver, method 2 had the lowest V30 with a mean ratio of 0.857 (SD = 0.1) whereas
      method 4 had the highest with 1.672 (SD = 0.48). For the spinal cord, method 3
      had the lowest mean dose ratio of 0.559 (SD = 0.09) whereas method 2 had the
      highest with 1.094 (SD = 0.04). Conclusion The four radiation techniques for
      esophageal cancer treatment were appropriate for target coverage. Method 2 had
      the most organ-sparing effect for the lungs and liver, and method 3 for the heart
      and spinal cord. VMAT did not add any significant sparing. A case-by-case
      decision should be made based on the patient's comorbidities.

PMID- 30237947
TI  - Slurring of Speech and Lip Paresthesia: Symptoms of Levodopa End of Dose Wearing
      Off in Parkinson's Disease.
AB  - The prolonged use of levodopa for treating Parkinson's disease is associated with
      motor and nonmotor complications. These include wearing-off, delayed-on, partial
      on, no-on, and on-off phenomena. In the wearing-off effect, symptoms return
      before a patient's next scheduled dose of levodopa. Patients may present with
      motor, sensory, or autonomic fluctuations. In this report, we present a female
      patient experiencing numbness of lips and slurred speech as a symptom of wearing
      off effect. The major differential for sudden numbness of lips and slurred speech
      includes transient ischemic attacks. Therefore, it is imperative to identify the
      cause of these episodes so that appropriate treatment can be initiated. Our
      patient underwent extensive cardiac and neurological investigations, the findings
      of which were unremarkable. Her symptoms were likely due to levodopa wearing-off.
      Her condition improved on changing her levodopa to a sustained release form with
      more frequent dosing along with the addition of ropinirole to her treatment
      regimen.

PMID- 30237948
TI  - Acute Intermittent Porphyria: A Rare Cause of Acute Disseminated
      Encephalomyelitis.
AB  - Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the
      central nervous system (CNS) with no distinct etiology but implications include
      infections and commonly administered vaccinations. In this case report, we
      present the case of ADEM in a young female who was subsequently diagnosed with
      acute intermittent porphyria (AIP) that was the instigator of the initial CNS
      assault. Our case highlights the peculiar presentation of ADEM which can present
      as a diagnostic challenge and brings forth AIP as a new and previously unknown
      affiliate of this rare CNS disease. We also discuss the pathophysiology,
      diagnostic criteria, and subsequent treatment options for this rare clinical
      entity.

PMID- 30237949
TI  - Mid-ventricle Takotsubo in a Patient with Goodpasture Syndrome.
AB  - Takotsubo syndrome (TTS) is characterized by transient, regional systolic
      dysfunction of the left ventricle, often mimicking acute coronary syndrome.
      Atypical variants of this syndrome with mid-ventricular, basal, and focal wall
      motion patterns are increasingly diagnosed and show different clinical features
      compared to typical TTS. Even though TTS was generally considered a benign
      condition, continuous and strict monitoring is necessary to diagnose potentially
      life-threating complications. This is the first case report, to our knowledge, of
      atypical TTS in a patient with Goodpasture syndrome triggered by acute kidney
      injury (AKI).

PMID- 30237950
TI  - Wernicke Encephalopathy Due to Hyperemesis Gravidarum in Pregnancy: A Case
      Report.
AB  - Wernicke's encephalopathy (WE) is a life-threatening acute or sub-acute
      neurological emergency characterized by ataxia, confusion, nystagmus, and
      ophthalmoparesis caused by thiamine deficiency. It was first described in 1881 by
      Carl Wernicke with alcohol being the most common cause. We present a rare case of
      a 35-year-old pregnant female who presented to our emergency department with a
      history of vomiting and loose motions for two weeks. She later developed fever,
      confusion, slurred speech and blurring of vision. Magnetic resonance imaging
      (MRI) of the brain revealed typical lesions of WE. She was immediately treated
      with thiamine and her symptoms improved in a few days.

PMID- 30237951
TI  - Laparoscopic Sleeve Gastrectomy: To Suture or not to Suture Staple Line?
AB  - Objective To assess the outcome and safety of staple line over-sewing for
      patients undergoing laparoscopic sleeve gastrectomy (LSG). Study design and
      location Retrospective descriptive analysis conducted at Shifa International
      Hospital Islamabad. Materials and methods Consecutive patients undergoing LSG as
      a treatment for morbid obesity from October 2013 to December 2016 were included
      in the study after approval from the ethical review board. Patients were divided
      into two groups: group A who underwent reinforcement using Vicryl 2.0 and group B
      where no reinforcement was done. Results A total of 225 patients underwent LSG
      between October 2013 and December 2016, including 147 females (65.4%) and 78
      males (34.6%). Both groups were comparable in terms of age, body mass index (BMI)
      and gender distribution (p-value more than 0.05). There was one leak in group A
      (1.36%), none in group B. The bleeding rate was 4.3% in group A and 2.7% in group
      B. Conclusion This was a retrospective analysis of all the patients who underwent
      LSG, and it was observed that there was no added benefit of sewing the staple
      line in terms of rate of bleeding and leak.

PMID- 30237952
TI  - Topographic Expressions of Large Thrust Faults on Mars.
AB  - On planets with little erosion, thrust faults produce broad, asymmetric, positive
      relief, linear to arcuate ridges -often referred to as lobate scarps- that remain
      largely unaltered, such that their topographic expressions are a measure of the
      structural uplift caused by the displacement and associated country-rock
      deformation of the faults. Here we map and systematically assess the structural
      relief of 24 thrust faults across Mars to infer their growth behavior. Our
      mapping indicates that the majority of individual thrust faults have simple,
      linear map traces with lengths of up to ~450 km, but that some thrust faults form
      systems of up to 1400 km in length. For the most topographically pronounced
      landforms, the structural relief developed above the fault is as great as ~3400
      m. We then relate topographic measurements to the displacement on the underlying
      fault planes to study the displacement variations along the fault length. We find
      a variety of displacement distribution shapes of the fault systems, which we
      attribute to differences in fault growth that include unrestricted and restricted
      growth, linkage, and/or fault interaction. Finally, we relate the maximum
      displacements (Dmax ) determined for each of the faults to their respective fault
      length (L) to establish a maximum displacement-to-length relationship. The
      observed scaling characteristics and order-of-magnitude scatter of our Dmax/L
      data are not uncommon for fault populations on Earth and tie in well with the map
      patterns, tectonic geomorphology, and systematic along-strike displacement
      distributions to have grown in a basement-block faulting style found in intra
      plate tectonic settings on Earth.

PMID- 30237953
TI  - The draft genome sequence of Clostridium sp. strain LJ4 with high furan and
      phenolic derivates' tolerances occurring from lignocellulosic hydrolysates.
AB  - The genome of a wild-type solventogenic Clostridium sp. strain LJ4 that could
      directly convert undetoxified lignocellulosic hydrolysate to butanol and tolerate
      high concentration of furan and phenolic derivates occurring in the
      lignocellulosic hydrolysate is described. 16S rDNA gene sequencing and analysis
      indicated that it is closely related to Clostridium acetobutylicum. The genome
      size of strain LJ4 is 3.90 Mp, which has a G + C content of 30.72% and encodes
      2711 proteins. It also has one 0.19 Mp plasmid with 181 predicted encoding
      proteins. Alcohol dehydrogenases (ADs) and a nicotinamide adenine dinucleotide
      phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase were
      identified, which may play key roles in inhibitors' resistance in lignocellulosic
      hydrolysate.

PMID- 30237954
TI  - Improving palm kernel cake nutrition using enzymatic hydrolysis optimized by
      Taguchi method.
AB  - Enzymatic hydrolysis of palm kernel cake to improve the quality of substrates
      with multi-response criteria based on the Taguchi orthogonal array. Nine
      experimental runs were performed based on an L9 orthogonal array. Percent
      substrate, incubation time, and enzyme units were optimized considering multiple
      performance characteristics. Analysis of variance was also applied to identify
      the most significant factors. Results determined percent substrate as the most
      important factor for enzymatic hydrolysis followed by incubation time and enzyme
      units. Enzymatic hydrolysis conditions were optimized as percent substrate,
      incubation time and enzyme units at 14%, 6 h and 750 units, respectively. Tests
      were conducted to compare experimental and model results. The experimental result
      (protein release) at optimal condition were three times higher than the predicted
      mode.

PMID- 30237955
TI  - Genetic variations of the Hemagglutinin gene of Pandemic Influenza A (H1N1)
      viruses in Assam, India during 2016.
AB  - Since its emergence in 2009, Influenza A/H1N1pdm09 virus has evolved
      continuously. Marked genetic variations have occurred in the HA1 domain of the
      hemagglutinin gene causing the emergence of new variants. The present study
      genetically characterized the hemagglutinin (HA) gene of Influenza A/H1N1pdm09
      strains from Assam circulating in 2016 that caused a mild outbreak without any
      reported mortality. Sequence analysis of the HA gene of 20 positive
      Assam/H1N1pdm09 strains revealed 3 mutations (K180Q, S202T, S220T) at the
      antigenic sites along with several other reported mutations which are in close
      proximity to the antigenic sites and therefore might affect the viral
      antigenicity. Phylogenetically, the Assam/H1N1pdm09 strains clustered into
      genogroup 6B. These genetic variations highlight the importance of continuous
      surveillance and characterization of Influenza A/H1N1pdm09 virus activity to
      track the genetic makeup and diversification that may affect the behavior of the
      virus.

PMID- 30237956
TI  - Immunomodulation of IL-1, IL-6 and IL-8 cytokines by Prosopis juliflora alkaloids
      during bovine sub-clinical mastitis.
AB  - The current work is focused on establishing therapeutic protocol using
      unconventional drugs of herbal origin and studying their mechanism of action at
      molecular level in the treatment of bovine sub-clinical mastitis. It explores the
      potential of different cytokines which can be used for diagnosis, prognosis and
      monitoring of bovine sub-clinical mastitis. Prosopis juliflora alkaloids was
      administered intramammarily in 24 sub-clinically affected quarters once a day for
      5 consecutive days at the rate of 10 ml of 1% formulation. In 18 disease control
      quarters, sterile normal saline was infused. The bacterial cultural examination,
      somatic cell count (SCC) and cytokines (IL-1beta, IL-6, IL-8, IL-12, GM-CSF, IFN
      gamma, TNF-alpha) expression by real-time PCR were evaluated on day 7, 14, 21 and
      28 post-last treatment from milk samples. Around 75.0% of treatment group
      quarters showed significant (p < 0.05) reduction in SCC on day 28 post-last
      treatment, whereas 94.4% control group quarters did not show any significant
      decline in SCC. 58.3% of treated quarters showed both bacteriological cure as
      well as significant (p < 0.05) reduction in SCC on day 28 post-last treatment.
      While, among control group quarters, 83.3% quarters not only remained
      bacteriological positive, they also did not show any significant decline in SCC.
      The in vitro antimicrobial activity of alkaloids of P. juliflora was evaluated.
      Lower concentrations of alkaloids (0.25% and 0.50%) dissolved in normal saline
      showed zone of inhibition against 12 out of 15 isolates, however higher
      concentration (1, 1.5, 2, 2.5 and 5%) showed zone of inhibition against all 15
      bacterial isolates. The gene expression level of IL-1beta, IL-8 and IFN-gamma
      cytokines exhibited significant difference between healthy and sub-clinically
      affected quarters highlighting the potential of these cytokines in the diagnosis
      of bovine sub-clinical mastitis. Down-regulation of IL-1, IL-6, IL-8 and IFN
      gamma cytokines in treated quarters can be explored for making the prognosis and
      monitoring post-treatment disease progression of bovine sub-clinical mastitis.
      The P. juliflora alkaloid demonstrated strong in vitro and in vivo antibacterial
      activity, along with causing immunomodulation by enhancing post-treatment gene
      expression of IL-1, IL-6 and IL-8 cytokines. Therefore, P. juliflora alkaloids
      hold a strong claim as an effective alternative herbal therapy in bovine sub
      clinical mastitis.

PMID- 30237957
TI  - Containment evaluation, cold tolerance and toxicity analysis in Osmotin
      transgenic tomato (Solanum lycopersicum L. cv. Pusa Ruby).
AB  - The present study reports engineered cold tolerance and toxicity analysis in
      genetically modified tomato (Solanum lycopersicum L. cv. Pusa Ruby) developed
      through constitutive over expression of Nicotiana tabacum Osmotin gene. Rate of
      seed germination, seedling establishment and growth remained unaffected in the
      transgenic tomato in response to a low temperature (15  degrees C) treatment, but
      were significantly (P <= 0.05) reduced in the wild type. At reproductive stage,
      the wild type plants failed to recover at the low temperature (4.0  degrees C)
      treatment for 10 days but the transgenic plants survived successfully without any
      leaf senescence or other visible chilling injury symptoms. The quantitative
      transcript expression analysis confirmed up regulation of the transgene by 55% in
      the transgenic plants on cold treatment for 2 h whereas, the transcripts were not
      detected in the wild type. Containment evaluation under normal environmental
      conditions revealed similar morphology in both the transgenic and wild type
      tomato plants however an average fruit yield was higher in the transgenic plants
      (725.91 +/- 39.27 g) than the wild type (679.84 +/- 28.80 g). The composition of
      mature fruits in terms of element content was at par in both the transgenic and
      wild type except significantly higher Ca and Mg contents in the transgenic fruits
      than that of the wild type. Further, acute and sub-acute toxicity tests conducted
      in the adult female Wister rats revealed no mortality or significant changes in
      general and psychological behaviour, at par food intake and body weight and,
      normal biochemical, and hematological parameters for animals fed with the wild
      type or transgenic tomato fruits as compared to the control group, confirming its
      safety for animal consumption.

PMID- 30237959
TI  - Elicitation of silver nanoparticles enhanced the secondary metabolites and
      pharmacological activities in cell suspension cultures of bitter gourd.
AB  - This study describes the influence of bio-synthesized silver nanoparticles
      (AgNPs) on phytochemicals and their pharmacological activities in the cell
      suspension cultures (CSC) of bitter gourd. To standardize the effect of sucrose,
      plant growth regulators, medium, AgNPs and growth kinetics for the biomass and
      bioactive compounds accumulation in CSC of bitter gourd. The medium comprising MS
      salts, sucrose (30 g/L) with 2,4-D (1.0 mg/L) and TDZ (0.1 mg/L) at 28 days of
      CSC was appropriate for biomass and bioactive compound accumulation. The contents
      of silver, malondialdehyde and hydrogen peroxide were highly elevated in AgNPs
      (10 mg/L)-elicited CSC when compared with non-elicited CSC. AgNPs (5 mg/L)
      elicited CSC extracts had significantly enhanced the production of total phenolic
      (3.5 +/- 0.2 mg/g), and flavonoid (2.5 +/- 0.06 mg/g) contents than in the
      control CSC extracts (2.5 +/- 0.1 and 1.6 +/- 0.05 mg/g). AgNPs (5 mg/L) elicited
      CSC showed a higher amount of flavonols (1822.37 ug/g), hydroxybenzoic (1713.40
      ug/g) and hydroxycinnamic (1080.10 ug/g) acids than the control CSC (1199,
      1394.42 and 944.52 ug/g, respectively). Because of these metabolic changes, the
      pharmacological activities (antioxidant, antidiabetic, antibacterial, antifungal
      and anticancer) were high in the AgNPs (5 mg/L)-elicited CSC extracts in bitter
      gourd. The study suggested the effectiveness of elicitation process in enhancing
      the accumulation of phenolic compounds and pharmacological activities. AgNPs
      elicited CSC offered an effective and favorable in vitro method to improve the
      production of bioactive compounds for potential uses in pharmaceutical
      industries.

PMID- 30237960
TI  - A resourceful methodology to profile indolic auxins produced by rhizo-fungi using
      spectrophotometry and HPTLC.
AB  - Plant growth-promoting fungi play an important role in development of sustainable
      agriculture. In the current study, 13 fungal strains were isolated from the
      rhizosphere of healthy Triticum aestivum (wheat) plant and screened for their
      indolic auxin production potential. Aspergillus flavus strain PGFW, Aspergillus
      niger strain BFW and Aspergillus caespitosus strain DGFW were amongst the most
      efficient indolic auxin-producing strains. Indolic auxins such as indole 3
      acetate (IAA), indole 3 butyrate (IBA) and indole 3 propionate (IPA) are produced
      by fungi. The conventional method to assess the IAA production is through a
      spectrophotometric assay using Salkowski's reagent, which quantifies all indolic
      auxins and not individual auxins. Moreover, it was also observed that the
      absorption maxima (lambdamax) of the samples, when compared to that of standard
      indole-3-acetic acid, showed deviation from the latter, indicative of production
      of a mixture of indolic derivatives by the fungi. Hence, for further profiling of
      these indolic compounds, high-performance thin layer chromatography (HPTLC) based
      protocol was standardized to precisely detect and quantify individual indolic
      auxins like IAA, IBA and IPA in the range of 100-1000 ng per spot. HPTLC analysis
      also showed that the fungal strains produce different indolic auxins in media
      with and without fortification of tryptophan, with the production of indolic
      auxins being enhanced in presence of tryptophan. Thus, this standardized HPTLC
      protocol is an efficient and sensitive methodology to separate and quantify the
      indolic derivatives.

PMID- 30237958
TI  - Silver nanoparticles as antimicrobial therapeutics: current perspectives and
      future challenges.
AB  - Utility of silver metal in antimicrobial therapy is an accepted practice since
      ages that faded with time because of the identification of a few silver resistant
      strains in the contemporary era. A successive development of antibiotics soon
      followed. However, due to an indiscriminate and unregulated use coupled with poor
      legal control measures and a dearth of expertise in handling the critical
      episodes, the antibiotics era has already seen a steep decline in the past
      decades due to the evolution of multi-drug resistant 'superbugs' which pose a
      sizeable challenge to manage with. Due to limited options in the pipeline and no
      clear strategy in the forefront, the aspirations for novel, MDR focused drug
      discovery to target the 'superbugs' arose which once again led to the rise of
      AgNPs in antimicrobial research. In this review, we have focused on the green
      routes for the synthesis of AgNPs, the mode of microbial inhibition by AgNPs,
      synergistic effect of AgNPs with antibiotics and future challenges for the
      development of nano-silver-based therapeutics.

PMID- 30237961
TI  - Cloning and expression of truncated ORF2 as a vaccine candidate against hepatitis
      E virus.
AB  - Hepatitis E virus infection is responsible for acute viral hepatitis and
      associated with high mortality and still birth in pregnant women in developing
      countries. We report expression of truncated forms of HEV ORF2 as potential
      vaccine candidates for nanoparticle-based delivery. These two truncated ORF2
      proteins (54 kDa and 26 kDa) have been reported to be highly immunogenic and can
      be used as nanoparticle-based vaccine candidate. The bacterial expressed protein
      was purified by affinity chromatography and further confirmed by western blot
      using anti-HEV antibody. The chitosan nanoemulsion was synthesized using
      ultrasonic waves. The nanoparticle size was found to be 120-160 nm and the
      entrapment efficiency of purified truncated ORF2 proteins within these
      nanoparticles was 70% (26 kDa) and 59% (54 kDa). In cell cytotoxicity analysis,
      100 ug/mL nanoemulsion was found suitable for cell viability in both HeLa and
      THP1 cell lines. Release kinetics of encapsulated proteins at physiological pH
      7.4 showed 26-59% and 9.7-40% release of 26 kDa and 54 kDa protein within 1 h
      that gradually increased with time (48 h). Encapsulated proteins were found to be
      unstable at pH 1.2.

PMID- 30237962
TI  - Genome-wide identification and characterization of seed storage proteins (SSPs)
      of foxtail millet (Setaria italica (L.) P. Beauv.).
AB  - We report the identification of 47 foxtail millet (Setaria italica (L.) P.
      Beauv.) seed storage proteins (SSPs) consisting of 14 albumins, 12 prolamins, 18
      globulins and 3 glutelins using computational approaches and compared their
      essential amino acid composition with 225 SSPs of rice, barley, sorghum and
      maize. Comparative analysis revealed several unique foxtail millet SSPs
      containing high amounts of essential amino acids. These include three 2s-albumin
      proteins containing 11.9%, 10.9%, 9.82% lysine, one 10-kDa prolamin containing
      20% methionine residues and one each 7S-globulin, 10-kDa prolamin, alpha-zein
      proteins containing 9.2% threonine, 9.35% phenylalanine and 2.5% tryptophan,
      respectively. High lysine containing albumins and high methionine containing
      prolamins were also detected in other cereals indicating that these SSPs are
      widespread in cereals. Phylogenetic studies revealed that the foxtail millet SSPs
      are closer to sorghum and maize. The lysine-rich albumins and the methionine-rich
      prolamins formed a separate cluster. Motif analysis of lysine-rich albumins
      displayed several lysine containing conserved motifs across cereals including
      foxtail millet. The 10-kDa prolamin protein containing 20% methionine was unique
      as it lacked the characteristic repeat motifs of methionine found in the high
      methionine containing zeins and kafirins. The motif "NPAAFWQQQQLL" was uniquely
      repeated in the foxtail millet high tryptophan prolamin protein. The findings of
      the present study provide new insights in foxtail millet seed storage protein
      characterization and their nutritional importance in terms of essential amino
      acid composition.

PMID- 30237963
TI  - Protein improvement of banana peel through sequential solid state fermentation
      using mixed-culture of Phanerochaete chrysosporium and Candida utilis.
AB  - Banana peel (BP) is a major waste produced by fruit processing industries. Pre
      treatment of BP at different temperatures led to 40% reduction in saponin at 100 
      degrees C (from 9.5 to 5.7 mg/g). Sequential mixed culture of Phanerochaete
      chrysosporium (P. chrysosporium) and Candida utilis (C. utilis) gave highest
      protein enrichment (88.93 mg/g). There is 26% increase in protein synthesis (from
      88.93 to 111.78 mg/g) after media screening. Inclusion of KH2PO4, FeSO4.7H2O,
      wheat flour and sucrose in the media contributed positively to protein synthesis,
      while elevated concentration of urea, peptone, K2HPO4, KCl, NH4H2PO4, and
      MgSO4.7H2O are required to reach optimum protein synthesis. Total soluble sugar
      (TSS), total reducing sugar (TRS) and total carbohydrate (CHO) consumption varied
      with respect to protein synthesis in all experimental runs. Optimum protein
      synthesis required 6 days and inclusion of 5% sucrose, 0.6% NH4H2PO4, 0.4% KCl,
      and 0.5% MgSO4.7H2O as concentration media constituents to reach 140.95 mg/g
      protein synthesis equivalent to 300% increase over the raw banana peel protein
      content (35.0 mg/g).

PMID- 30237964
TI  - Optimization of cultural conditions for lipid accumulation by Aspergillus wentii
      Ras101 and its transesterification to biodiesel: application of response surface
      methodology.
AB  - The present study is aimed to maximize biodiesel production by using the fungal
      strain Aspergillus wentii Ras101 as a feedstock. Response surface methodology was
      used to relate the interaction between some nutritional and environmental factors
      affecting the lipid productivity by A. wentii Ras101. By applying LINGO
      optimization program, the maximum lipid production of 40% dry biomass of this
      fungal isolate has been attained in a fermentation medium composed of 50 g/l
      glucose, 1 g/l nitrates, 1.5 g/l phosphorous, and 0.5 g/l NaCl. This medium was
      adjusted at pH of 6, and incubated at 28  degrees C for 7 days. The values of
      correlation errors between the experimental and estimated values are less than
      1%; this proves that the proposed correlation could be used effectively for
      estimating the fungal lipid production. Consequently, the effects of time and
      temperature on the amount of biodiesel produced in the extraction and
      transesterification one-step process have been investigated. The maximum
      biodiesel production of 28% dry biomass (80% lipid) has been achieved in the
      transesterification process at 70  degrees C for 30 min. Additionally, it is
      found that the combination of glucose, nitrogen and phosphorous contents has a
      positive influence on lipid production in the fungal biomass. The density,
      kinematic viscosity, water content and calorific value of the produced biodiesel
      were 800 kg/m3, 2.8 mm2/s, 66 ppm and 10122 kcal/kg, respectively that matched
      well with biodiesel and fossil standard specifications.

PMID- 30237965
TI  - Gibberellin-induced perturbation of source-sink communication promotes sucrose
      accumulation in sugarcane.
AB  - Constant removal of sugars from the site of synthesis (i.e., leaves), in response
      to elevated sink (culm) demand, may perhaps prevent damping of photosynthesis, by
      sugar, and hence promote further sucrose accumulation in the culm. In this study,
      gibberellic acid (GA3) induced nearly 42.3% enlargement in cell size and about
      39.3% increase in internodal length (sink capacity), 177% escalation in reducing
      sugar level (sink strength), amplified the expression of sucrose-metabolizing
      enzymes (sink demand), viz., 7.5-fold for SAI, 4.5-fold for CWI, sixfold for SPS,
      all demonstrating facilitation of augmented sucrose accumulation in the culm. The
      GA3-treated BO 91 cane (late maturing sugarcane variety) exhibited an elevated
      final sucrose concentration (40.54-41.6%) as compared to control (30.44-38.8%).
      The GA3-sprayed cane of early maturing Co J64 also showed such a boost, but it
      was lost by the end of maturity, perhaps due to inversion and/or the less
      effective GA3 treatment. Thus, results demonstrated the role of GA3 in augmenting
      sucrose content of cane culm, possibly by influencing source-sink dynamics in
      sugarcane.

PMID- 30237966
TI  - Symptom dimensions in obsessive-compulsive disorder as predictors of neurobiology
      and treatment response.
AB  - Purpose of review: Specific symptom dimensions of obsessive-compulsive disorder
      (OCD) have been suggested as an approach to reduce the heterogeneity of obsessive
      compulsive disorder, predict treatment outcome, and relate to brain structure and
      function. Here, we review studies addressing these issues. Recent findings: The
      contamination and symmetry/ordering dimensions have not been reliably associated
      with treatment outcome. Some studies found that greater severity of
      sexual/aggressive/religious symptoms predicted a worse outcome after cognitive
      behavioral therapy (CBT) and a better outcome after serotonin reuptake inhibitors
      (SRIs). Contamination symptoms have been related to increased amygdala and insula
      activation in a few studies, while sexual/aggressive/religious symptoms have also
      been related to more pronounced alterations in the function and structure of the
      amygdala. Increased pre-treatment limbic responsiveness has been related to
      better outcomes of CBT, but most imaging studies show important limitations and
      replication in large-scale studies is needed. We review possible reasons for the
      strong limbic involvement of the amygdala in patients with more
      sexual/aggressive/religious symptoms, in relation to their sensitivity to CBT.
      Summary: Symptom dimensions may predict treatment outcome, and patients with
      sexual/religious/aggressive symptoms are at a greater risk of not starting or
      delaying treatment. This is likely partly due to more shame and perceived
      immorality which is also related to stronger amygdala response. Competently
      delivered CBT is likely to help these patients improve to the same degree as
      patients with other symptoms.

PMID- 30237968
TI  - Comparison between low-dose chemotherapy and surgery for the treatment of
      extremity-associated solitary bone lesions in children with Langerhans cell
      histiocytosis in South China: A case-control study.
AB  - Background: The treatment algorithm for solitary bone lesions of Langerhans cell
      histiocytosis (SBL-LCH) in children extremities still remains controversial. We
      conducted a retrospective case-control study to compare the feasibility of low
      dose chemotherapy (LDC) and surgery for SBL-LCH in children extremities. Patients
      and methods: This study compares 43 pediatric patients starting LDC with a
      surgery control group (n = 44), matched for gender, age, follow-up time, and
      lesion sites and sizes, treated between 2001 and 2015 at our institution.
      Hospital stay (HS), time to symptom relief (TTSR), recovery time (RT),
      complications, relapse-free survival (RFS), health-related quality of life
      (HRQOL) and cost-effectiveness were analyzed for each strategy. Results: HS, TTSR
      and RT in the LDC group were shorter than those in the surgery group (p < 0.01).
      Chemotherapy-related complications included nausea (16.30%), aminotransferase
      elevation (9.30%), slight hair loss (11.63%), decline in immune function
      (23.26%), growth retardation (16.30%), and moon face (9.30%). Chemotherapy
      related side effects were mild and well tolerated. Pathologic fractures (6.81%),
      loosening of instrumentation (6.00%,), surgical site infection (4.00%) and
      rejection of bone grafting (9.09%) developed in surgery patients. LDC treatment
      resulted in a longer RFS (87 months) than surgery alone (59 months) (p = 0.011).
      Furthermore, compared with surgery patients, patients in the LDC group had a
      better HRQOL at 3 months' follow-up for the physical, role, emotional and social
      function domains assessed (p < 0.001, p = 0.001, p < 0.001 and p = 0.003,
      respectively) according to the European Organisation for Research and Treatment
      of Cancer QLQ-C30(r) survey. However, HRQOL scores at 2 years' follow-up were
      similar between the two groups. The incremental cost-effectiveness ratio (ICER)
      was Y-137,030/quality-adjusted life year (QALY) for LDC versus surgery.
      Conclusions: Compared with surgery, LDC promotes more rapid recovery, is less
      invasive, is characterized by increased safety and a superior HRQOL, and is a
      more cost-effective treatment strategy for pediatric patients with SBL-LCH in the
      extremities.

PMID- 30237967
TI  - A cross-sectional study on the relationship between the risk of hypertension and
      obesity status among pre-adolescent girls from rural areas of Southeastern region
      of the United States.
AB  - This study investigated early indications of hypertension risk and the
      association of overweight and obesity in young girls from a low socioeconomic
      region of the rural South. 139 females (M age = 8.85 +/- 1.67 years) from a rural
      school in the Southeastern region of the United States served as participants.
      Body mass index was calculated based on the child's height and weight
      measurements (kg/m2) and resting blood pressure measurements were taken with
      calibrated, automatic oscillations devices. Girls who were overweight or obese
      were 2.81 times more likely to have a systolic blood pressure indicative of being
      at-risk/hypertensive (i.e., pre-hypertension and/or hypertension stage 1) than
      girls who were not overweight/obese. In fact, the percentage of overweight/obese
      girls who were at-risk/hypertensive was double that of girls who were not
      overweight/obese (43.2% versus 21.3%), respectively. Being overweight or obese is
      associated with almost three times a higher risk of hypertension than girls who
      are not overweight or obese.

PMID- 30237969
TI  - Trends in incidence of Ewing sarcoma of bone in India - Evidence from the
      National Cancer Registry Programme (1982-2011).
AB  - Background: Ewing sarcoma is a malignant tumour found mainly in childhood and
      adolescence. The present study aims at analyzing the data on Ewing sarcoma cases
      of bone from the National Cancer Registry Programme, India to provide incidence,
      patterns, and trends in the Indian population. Materials and Methods: The data of
      five Population Based Cancer Registries (PBCR) of Bangalore, Mumbai, Chennai,
      Bhopal and Delhi over 30 years period (1982- 2011) were used to calculate the Age
      Specific and Age Standardized Incidence Rates (ASpR and ASIR), and trends in
      incidence was analyzed by linear and Joinpoint Regression. Results: Ewing sarcoma
      comprised around 15 % of all bone malignancies. Sixty-eight percent were 0-19
      years, with 1.6 times risk of tumour in bones of limbs as compared to other
      bones. The highest incidence rate (per million) was in the 10-14 years age group
      (male -4.4, female -2.9) with significantly increasing trend in ASpR observed in
      both sexes. Pooled ASIR per million for all ages was higher in male (1.6) than
      female (1.0) with an increasing rate ratio of ASIR with increase in age. Trend of
      pooled ASIR for all ages was significantly increased in both sexes. Twelve
      percent cases were reported in >=30 years of age. Conclusion: This paper has
      described population based measurements on burden and trends in incidence of
      skeletal Ewing in India. These may steer further research questions on the
      clinical and molecular epidemiology to explain factors associated with the
      increasing incidence of Ewing sarcoma bone observed in India.

PMID- 30237971
TI  - Emphysema formation in a never-smoker with scleroderma-related interstitial
      pneumonia.
AB  - We report a case of pathological emphysema formation in a never-smoker with
      scleroderma-related interstitial pneumonia. We realized the importance of
      pulmonary vasculopathy causing the coexistence of emphysema and fibrosis in
      scleroderma. Our discovery provides novel information that emphysema can occur in
      patients with scleroderma-related interstitial pneumonia who have never smoked.

PMID- 30237970
TI  - Cephalometric appraisal of the effects of orthodontic treatment on total airway
      dimensions in adolescents.
AB  - Aim: This retrospective study was performed to rule out any jeopardizing effect
      of extraction therapy of four first premolars on airway at any level of its
      anatomic course. Materials and methods: Lateral cephalograms of 50 adolescent
      patients divided into two groups of 25 each, based on orthodontic treatment by
      first premolar extraction as group I and without extraction as group II, were
      selected for the study. 13 angular and 11 linear measurements were compared pre
      and post-treatment via statistical analyses using SPSS (Version 17.5, SPSS,
      Chicago) software. Paired 't' tests were used to assess the variability. P-value
      < 0.05 was considered to be statistically significant. Results: Comparison of
      angular parameters showed that the average percentage (%) change in SNA, SNB,
      ANB, IMPA, FMA, saddle, articulare, gonial, total angle and hyoid did not differ
      significantly across two study groups (P > 0.05), but values of UI/LI, UI/NA,
      LI/NB, differed significantly among both groups. Similarly, linear parameters
      showed that the average % change in nasopharyngeal airway space (NAS) and width
      of soft palate differed significantly across two study groups (P-value<0.05),
      whereas the average % change in posterior airway space (PAS), hypopharyngeal
      airway space (HAS), hyoid distance and length of tongue did not differ
      significantly (P-value>0.05). However, no significant differences were observed
      during intragroup and intergroup comparisons of the combined angular and linear
      measurements of both groups. Conclusions: Present study showed no significant
      change on airway after therapeutic orthodontic tooth movement with or without
      extraction treatment.

PMID- 30237972
TI  - Acute pulmonary embolism and deep vein thrombosis secondary to idiopathic
      hypereosinophilic syndrome.
AB  - Acute pulmonary embolism (PE) is a most dangerous complication that needs prompt
      treatment to reduce potentially death. There are many well-known prognostic
      factors indicate the morbidity and mortality in various thromboembolic events.
      Persistent eosinophilia in peripheral blood can lead to tissue infiltration and
      even organ damage, but the urgent event of thromboembolism in pulmonary provoked
      by eosinophil eosinophilia in idiopathic hypereosinophilic syndrome (HES) is
      relative an unusual presentation. In this paper, we present two cases of patients
      with multiple PE and deep vein thrombosis secondary to the idiopathic HES.
      Patients were all treated using anticoagulant therapy and corticosteroids
      successfully. Accordingly, eosinophilia is another risk and precipitating factor
      of pulmonary thromboembolism. It is necessary for physicians to make a diagnosis
      in hypereosinophilia as soon as possible for proper prognosis and in case of
      further thromboembolic events and prevent end-organ damage.

PMID- 30237973
TI  - Miliary tuberculosis mimicking systemic lupus erythematosus flare.
AB  - A 26-year-old woman was diagnosed with and treated for systemic lupus
      erythematosus (SLE) in 2002. She was admitted 11 years later with nephrotic-range
      proteinuria and lupus nephritis and received two doses of rituximab after failing
      on steroids and mycophenolate mofetil. Four months later, she presented with
      fever and joint pain/swelling. Gram stains, joint aspirates, and blood culture
      all yielded negative results for bacteria. She was discharged after treatment for
      a possible flare of lupus, but two weeks later, she presented again with a cough
      and shortness of breath in addition to the flare symptoms. Synovial fluid Smears,
      and cultures yielded positive results for Mycobacterium tuberculosis; similarly,
      sputum polymerase chain reaction test and culture confirmed pulmonary
      tuberculosis. Tuberculosis is difficult to diagnose in SLE patients; it may
      present like or precipitate SLE flare. In this patient a presumed SLE flare
      turned out to be an aggressive miliary, disseminated tuberculosis.

PMID- 30237974
TI  - Outcomes of extracorporeal membrane oxygenation in adult patients with hypoxemic
      respiratory failure refractory to mechanical ventilation.
AB  - Introduction: Extracorporeal membrane oxygenation (ECMO) is a mode of
      extracorporeal life support that has been used to support cardiopulmonary disease
      refractory to conventional therapy. The experience with the use of ECMO in acute
      hypoxemic respiratory failure is still limited. The aim of this study was to
      report clinical outcomes in adult patients with acute hypoxemic respiratory
      failure refractory to mechanical ventilation treated with ECMO. Methods: Between
      July 2011 and October 2017, 18 adult patients with hypoxemic respiratory failure
      refractory to mechanical ventilation were admitted to the Intensive Care Unit of
      an acute care tertiary hospital in Barcelona, Spain. These patients were treated
      with ECMO as salvage respiratory therapy. Outcomes included clinical data,
      ventilatory and blood gas characteristics, survival, and complications. Results:
      Fifteen patients (83.3%) were previously treated in prone position. The
      indication of VV-ECMO was established at an early stage after a mean (SD) of 3.8
      (2.5) days on mechanical ventilation. The mean duration of ECMO was 10.4 days,
      and 16 patients (88.9%) required venous cannulation, mostly femoral-internal
      jugular. The mean length of ICU stay was 27 days and the mean hospital stay was
      42.1 days. The ICU survival rate was 55.5% (n = 10) and the hospital survival
      rate was 50% (n = 9). Conclusions: This clinical study in a small series of ICU
      patients treated with ECMO confirms the usefulness of this technique as a
      ventilatory support in patients with refractory hypoxemic respiratory failure.
      However, the indication of this procedure is also committed to an ethical
      reflection considering the possible futility of the measure on a case-by-case
      basis and associated complications.

PMID- 30237975
TI  - Candida dubliniensis: A novel cause of fungal keratitis.
AB  - A 45-year-old female with history of contact lens wear presented with a
      persistent corneal ulcer that was unresponsive to topical moxifloxacin. The
      patient's exam was concerning for fungal keratitis. Cultures were obtained, and
      the patient was started on fortified amphotericin B drops and oral voriconazole.
      The cultures identified Candida dubliniensis as the causative organism. The
      patient's exam worsened despite treatment, and the decision was made for surgery.
      At the time of surgery, her cornea was found to have unexpectedly perforated. She
      underwent cryotherapy; tectonic penetrating keratoplasty; anterior chamber tap;
      intracameral voriconazole, amphotericin B, and cefuroxime; and a partial
      conjunctival flap. Pathology from the cornea showed GMS and PAS stains positive
      for fungal forms. C. dubliniensis is a yeast closely related to Candida albicans
      that was first described in 1995 as a cause of oral candidiasis in patients with
      AIDS. There are a few published cases of endophthalmitis due to C. dubliniensis
      in the ophthalmology literature, but to our knowledge, no cases of fungal
      keratitis due to this organism have been reported. C. dubliniensis is a novel
      cause of fungal keratitis that can be difficult to identify and treat but is felt
      to be less virulent than C. albicans and generally susceptible to available anti
      fungal therapies.

PMID- 30237976
TI  - Breast filariasis.
AB  - Filariasis is a global health problem and is a major social and economical burden
      in tropical countries in Asia, Africa and few of the South American countries
      [1,2]. In india, filariasis endemic in number of states including Bihar, Kerala,
      Uttar Pradesh, Andhra Pradesh and Tamil Nadu is found chiefly along the banks of
      rivers and sea coastal areas. We present a case of 28 year female patient who
      presented with lump in her left breast for three months and was not associated
      with pain or discharge from nipple. Fine needle aspiration cytology (FNAC) showed
      live adult filarial worm along with various stages of filariasis such as
      microfilaria, adult filaria and embryonated eggs of adult gravid female worm. In
      the world the largest number of filarial cases occur in India and about 600
      million people live in endemic areas. Despite the huge number of people affected
      worldwide, it is quite rare to find microfilaria in routine cytological smears
      and body fluids. Filariasis of the breast is an uncommon condition and can cause
      a diagnostic dilemma. Hence, a high index of suspicion, particularly in patient
      from endemic areas, should be kept in mind so as to avoid surgical measures.

PMID- 30237977
TI  - Early hydrocephalus in Listeria meningitis: Case report and review of the
      literature.
AB  - Listeria monocytogenes is a gram-positive bacterium with a predilection to infect
      the central nervous system, often affecting immunocompromised or elderly
      patients. The most common manifestations are meningitis and rhomboencephalitis.
      We report two cases of Listeria meningitis complicated by acute hydrocephalus
      several days after presentation and we further review the literature of similar
      cases. We conclude that acute hydrocephalus is a significant, not often
      recognized, complication of Listeria meningitis, usually occurring several days
      from onset when coverage did not include anti-Listeria antimicrobials. In high
      risk patients, meningitis combined with acute hydrocephalus is suggestive of LM
      infection.

PMID- 30237978
TI  - Heat induced epitope retrieval for rabies virus detection by direct fluorescent
      antibody test in formalin-fixed dog brain tissues.
AB  - There is a great need for a chemical method of tissue preservation that would
      allow sample storage for extended periods at room temperature. This study aimed
      at retrieving and detecting rabies virus antigen by direct fluorescent antibody
      test (DFAT) in formalin-fixed dog brain tissues. Forty fresh dog brain specimens
      were collected as paired samples from rabies suspected cases that were received
      for postmortem detection of rabies in the Central Diagnostic Laboratory, National
      Veterinary Research Institute, Vom. One portion of each paired sample was
      prepared for fresh fluorescent antibody testing and the other portion was
      prepared for epitope retrieval and florescent antibody testing following fixation
      in 10% neutral buffered formalin. DFAT on formalin-fixed tissue exhibited a
      sensitivity of 100% in comparison to DFAT on fresh-tissue. No false positive
      result was obtained in formalin-fixed DFAT procedure, demonstrating 100%
      specificity. There was no apparent difference in the intensity of fluorescence in
      DFAT on fresh sample and formalin-fixed DFAT following heat induced epitope
      retrieval (concordance = 98%; 95% C.I. 0.9660 to 0.9903). The strength of
      agreement between DFAT on formalin-fixed and DFAT on fresh tissue was very good
      (Cohen's kappa coefficient value= 1.000; 95% C.I. 1.000-1.000). This study
      provides new information on the retrieval of rabies antigen by heat induced
      epitope retrieval for DFAT on formalinized tissues. Formalin could therefore, be
      used henceforth to fix tissues of rabies suspected cases for routine diagnosis,
      transportation or archival purposes. The heat induced epitope retrieval can be
      routinely used to retrieve rabies virus antigen for DFAT in cases where only
      formalin-fixed tissues are available or when preservation by freezing is
      difficult.

PMID- 30237979
TI  - Reliability of symmetric dimethylarginine in dogs with myxomatous mitral valve
      disease as kidney biomarker.
AB  - The most common cause of heart failure in the canine population is myxomatous
      mitral valve disease, sometimes complicated by chronic kidney disease. Many
      studies have been done on the use of symmetric dimethylarginine as biomarker of
      renal impairment in dogs affected by chronic kidney disease, few studies have
      examined his reliability as biomarker in dogs affected by heart diseases. Aim of
      this study was to evaluate symmetric dimethylarginine in dogs affected by mitral
      valve disease in order to assess his reliability in heart diseases. This was a
      retrospective case-control study on a clinical population of dogs affected by
      mitral valve disease (cases) vs healthy dogs (controls). Both groups underwent a
      complete physical evaluation, echocardiographic examination, complete blood
      count, biochemical panel, including serum creatinine and urea and urine analysis
      with protein-to-creatinine ratio. Serum was frozen and sent to IDEXX laboratories
      for symmetric dimethylarginine determination. General linear model was applied to
      data. A total number of 24 cases and 7 controls were included. Symmetric
      dimethylarginine value was in the reference value in the 75% (n=18) of cases, and
      in the 43% (n=3) of controls. Once set symmetric dimethylarginine as dependent
      variable, no statistical significant differences were found for each variable
      considered (breed, age, sex, weight, class of cardiomyopathy, presence/absence of
      valvular disease, presence/absence of congestive heart failure, pharmacological
      therapy, creatinine and urea concentration). Blood concentration of SDMA resulted
      not influenced by the variables mentioned above, so it could be considered a
      reliable marker of early renal impairment in dogs affected by mitral valve
      disease.

PMID- 30237980
TI  - Isolation and preservation of multipotent mesenchymal stem cells from bone marrow
      of Arabian leopard (Panthera pradus nimr).
AB  - The Arabian leopard (Panthera pardus nimr) is critically endangered by the
      International Union for Conservation of Nature, with an effective population of
      150-250 across its entire range in the Arabian Peninsula. Isolation and
      preservation of multipotent mesenchymal stem cells is beneficial both for medical
      and research purposes. The optimal protocol for collection, handling, culturing
      and preserving the Arabian leopard mesenchymal stem cells acquired from bone
      marrow was established. Anesthesia with combination of medetomidine and
      tiletamine-zozalepam is the safest option even for old animals with concurrent
      disease including chronic kidney disease.

PMID- 30237982
TI  - Editorial: Harnessing the Power of Patient Derived Models of Cancer.

PMID- 30237981
TI  - Blood hematological values of Barb horses in Algeria.
AB  - The Barb horse this famous Maghreb horse, symbol of the pride of the Berber
      peoples It is particularly significant in the Algerian history, tradition and
      culture. This study consists in establishing the hematologic values specific to
      the Barb horse in the national stud farm "Chaou-Chaoua" in Tiaret. Algeria. Age
      of the study animals varied between 1 and 23 years. The effects of age and sex
      were analyzed by dividing animals into four groups, A (1 - 2 years, n=5), B (3-5
      years, n=5), C (5-10 years, n=5) and D (11-23 years, n=5); for females and E (2 -
      3 years, n=5), F (5-7, n=5), G (10, n=5) and H (11-25, n=5) for males. Animals
      studied were clinically healthy. A blood sampling was carried out from all study
      animals, the following hematologic variables have been determined: erytrocytes
      (RBC), hematocrit (Ht), hemoglobin (Hb), mean cell volume (MCV), mean corpuscular
      hemoglobin concentration (MCHC), mean hemoglobin content (MHC), white blood cells
      (WBC), neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets,
      total number of platelets (PLT) and mean platelet volume (MPV). The obtained
      results showed that the hematologic values are within established standards for
      the other breeds of hot-blooded horses; these values approached the lower limits
      of the standards for the RBCs, HCT, Hb, WBCs and the lymphocytes. Statically
      significant (P<0.05) differences were observed between females in different age
      groups for the MCV, MCHC, Platelets and the MPV. Groups of males showed
      significant differences for lymphocytes and platelets and between males and
      females, significant differences related to the MCV, Neutrophils, Basophils
      Monocytes, Platelet and the MPV. This research showed that these hematologic
      parameters are weak, they approach the lower limits of the standards and that
      neither the age, nor the sex seem to have an influence on the hematologic values
      of the Barb horse.

PMID- 30237984
TI  - Integrated Analysis of a Competing Endogenous RNA Network Revealing a Prognostic
      Signature for Cervical Cancer.
AB  - Given the high morbidity and the trend of younger individuals being affected
      observed in cervical cancer, it is important to identify sensitive and effective
      biomarkers for predicting the survival outcome of patients. Based on data from
      307 cervical cancer cases acquired from The Cancer Genome Atlas portal, 1920
      differentially expressed mRNAs, 70 microRNAs(miRNAs), and 493 long non
      coding(lncRNAs) were screened by comparing cervical cancer tissues with
      paracancerous tissues. A competing endogenous (ceRNA) network containing 50
      lncRNAs, 16 miRNAs, and 81 mRNAs was constructed. Eighteen RNAs, comprising 13
      mRNAs, 2 miRNAs, and 3 lncRNAs, were identified as significant prognostic factors
      by univariate Cox proportional hazards regression. ETS-related gene and fatty
      acid synthase signatures were discovered using a multivariate Cox regression
      model built to identify independent prognostic factors in cervical cancer
      patients. Receiver operating characteristic (ROC) analysis was used to determine
      the optimal cut-off value for distinguishing the risk level of cervical cancer
      patients. High-risk patients exhibited a poorer prognosis than low-risk patients
      did. This study focused on ceRNA networks to provide a novel perspective and
      insight into cervical cancer and suggested that the identified signature can
      serve as an independent prognostic biomarker in cervical cancer.

PMID- 30237983
TI  - Multiple Roles of Glycans in Hematological Malignancies.
AB  - The three types of blood cells (red blood cells for carrying oxygen, white blood
      cells for immune protection, and platelets for wound clotting) arise from
      hematopoietic stem/progenitor cells in the adult bone marrow, and function in
      physiological regulation and communication with local microenvironments to
      maintain systemic homeostasis. Hematological malignancies are relatively uncommon
      malignant disorders derived from the two major blood cell lineages: myeloid
      (leukemia) and lymphoid (lymphoma). Malignant clones lose their regulatory
      mechanisms, resulting in production of a large number of dysfunctional cells and
      destruction of normal hematopoiesis. Glycans are one of the four major types of
      essential biological macromolecules, along with nucleic acids, proteins, and
      lipids. Major glycan subgroups are N-glycans, O-glycans, glycosaminoglycans, and
      glycosphingolipids. Aberrant expression of glycan structures, resulting from
      dysregulation of glycan-related genes, is associated with cancer development and
      progression in terms of cell signaling and communication, tumor cell dissociation
      and invasion, cell-matrix interactions, tumor angiogenesis, immune modulation,
      and metastasis formation. Aberrant glycan expression occurs in most hematological
      malignancies, notably acute myeloid leukemia, myeloproliferative neoplasms, and
      multiple myeloma, etc. Here, we review recent research advances regarding
      aberrant glycans, their related genes, and their roles in hematological
      malignancies. Our improved understanding of the mechanisms that underlie aberrant
      patterns of glycosylation will lead to development of novel, more effective
      therapeutic approaches targeted to hematological malignancies.

PMID- 30237987
TI  - Snyder-Robinson syndrome.
AB  - Snyder-Robinson syndrome, also known as spermine synthase deficiency, is an X
      linked intellectual disability syndrome (OMIM #390583). First described by Drs.
      Snyder and Robinson in 1969, this syndrome is characterized by an asthenic body
      habitus, facial dysmorphism, broad-based gait, and osteoporosis with frequent
      fractures. We report here a pediatric autopsy of a 4 year old male with a history
      of intellectual disability, gait abnormalities, multiple fractures, and seizures
      previously diagnosed with Snyder-Robinson syndrome with an SMS gene mutation
      (c.831G>T:p.L277F). The cause of death was hypoxic-ischemic encephalopathy
      secondary to prolonged seizure activity. Although Snyder-Robinson syndrome is
      rare, the need to recognize clinical findings in order to trigger genetic testing
      has likely resulted in under diagnosis.

PMID- 30237986
TI  - Joint Genomic and Proteomic Analysis Identifies Meta-Trait Characteristics of
      Virulent and Non-virulent Staphylococcus aureus Strains.
AB  - Staphylococcus aureus is an opportunistic pathogen of humans and warm-blooded
      animals and presents a growing threat in terms of multi-drug resistance. Despite
      numerous studies, the basis of staphylococcal virulence and switching between
      commensal and pathogenic phenotypes is not fully understood. Using genomics, we
      show here that S. aureus strains exhibiting virulent (VIR) and non-virulent
      (NVIR) phenotypes in a chicken embryo infection model genetically fall into two
      separate groups, with the VIR group being much more cohesive than the NVIR group.
      Significantly, the genes encoding known staphylococcal virulence factors, such as
      clumping factors, are either found in different allelic variants in the genomes
      of NVIR strains (compared to VIR strains) or are inactive pseudogenes. Moreover,
      the pyruvate carboxylase and gamma-aminobutyrate permease genes, which were
      previously linked with virulence, are pseudogenized in NVIR strain ch22. Further,
      we use comprehensive proteomics tools to characterize strains that show opposing
      phenotypes in a chicken embryo virulence model. VIR strain CH21 had an elevated
      level of diapolycopene oxygenase involved in staphyloxanthin production
      (protection against free radicals) and expressed a higher level of immunoglobulin
      binding protein Sbi on its surface compared to NVIR strain ch22. Furthermore,
      joint genomic and proteomic approaches linked the elevated production of
      superoxide dismutase and DNA-binding protein by NVIR strain ch22 with gene
      duplications.

PMID- 30237988
TI  - The lethal twist - a story of unspoken pain: small intestinal volvulus in
      cerebral palsy.
AB  - Small intestinal volvulus (SBV) is the abnormal twisting of bowel around the axis
      of its mesentery, leading to obstruction and vascular compromise, resulting in
      bowel ischemia and necrosis which are life-threatening. Risk factors include
      malformation, malrotation, and adhesions. Its rare incidence and vague clinical
      presentation make it a difficult diagnosis, more so in a nonverbal patient who
      cannot express his pain, which is the first and most prominent symptom. Studies
      suggest an increased frequency of intestinal obstruction in cerebral palsy
      patients. There are no reported cases of small intestinal volvulus in association
      with cerebral palsy. We present a case of a 21-year-old man with severe cerebral
      palsy and kyphoscoliosis. The patient presented to the emergency room with
      respiratory distress and abdominal distension. An acute abdomen was noted.
      Abdominal X-rays revealed gas patterns suggestive of small intestinal
      obstruction. The patient rapidly deteriorated, and resuscitation attempts were
      unsuccessful. Autopsy revealed peritoneal cavity filled with extensively dilated
      and thin-walled loops of small intestine. Twisting of the small intestine,
      showing 360 degrees  rotation around the mesenteric root in a clockwise manner at
      two separate sites, was noted. On bowel dissection, mucosal folds were absent,
      and mucosa was green with patchy areas of hemorrhage consistent with ischemic
      necrosis. There was no evidence of any malformation, malrotation or adhesions.
      Small intestinal volvulus is a rare entity with a nonspecific clinical
      presentation that poses a diagnostic challenge. This autopsy highlights the need
      to maintain a high index of suspicion for small intestinal volvulus in cases of
      bowel obstruction in cerebral palsy patients to expedite surgery and prevent
      mortality. The primary caregivers of non-verbal cerebral palsy patients living
      outside of healthcare facilities need to be trained in recognition of life
      threatening medical emergencies such as gastrointestinal obstruction and seek
      emergent attention at the earliest to prevent treatment delays.

PMID- 30237985
TI  - Biomarkers Associated With Leishmania infantum Exposure, Infection, and Disease
      in Dogs.
AB  - Canine leishmaniosis (CanL) is a vector-borne disease caused by the protozoan
      Leishmania (Leishmania) infantum species [syn. L. (L.) infantum chagasi species
      in the Americas] which is transmitted by the bite of a female phlebotomine sand
      fly. This parasitosis is endemic and affect millions of dogs in Asia, the
      Americas and the Mediterranean basin. Domestic dogs are the main hosts and the
      main reservoir hosts for human zoonotic leishmaniosis. The outcome of infection
      is a consequence of intricate interactions between the protozoan and the
      immunological and genetic background of the host. Clinical manifestations can
      range from subclinical infection to very severe disease. Early detection of
      infected dogs, their close surveillance and treatment are essential to control
      the dissemination of the parasite among other dogs, being also a pivotal element
      for the control of human zoonotic leishmaniosis. Hence, the identification of
      biomarkers for the confirmation of Leishmania infection, disease and
      determination of an appropriate treatment would represent an important tool to
      assist clinicians in diagnosis, monitoring and in giving a realistic prognosis to
      subclinical infected and sick dogs. Here, we review the recent advances in the
      identification of Leishmania infantum biomarkers, focusing on those related to
      parasite exposure, susceptibility to infection and disease development. Markers
      related to the pathogenesis of the disease and to monitoring the evolution of
      leishmaniosis and treatment outcome are also summarized. Data emphasizes the
      complexity of parasite-host interactions and that a single biomarker cannot be
      used alone for CanL diagnosis or prognosis. Nevertheless, results are encouraging
      and future research to explore the potential clinical application of biomarkers
      is warranted.

PMID- 30237989
TI  - Odontogenic myxoma in a child treated with enucleation and curettage.
AB  - Odontogenic myxoma is an aggressive benign odontogenic tumor, accounting for 3-6%
      of all the odontogenic tumors in adults. The incidence among children is lower.
      Due to its clinical behavior, there is no consensus on the best treatment. In
      this paper, the authors report the case of a 9-year-old girl with the diagnosis
      of odontogenic myxoma. The panoramic X-ray showed an extensive radiolucent lesion
      involving the left mandibular body causing teeth displacement. The treatment
      consisted of tumor enucleation followed by vigorous curettage of the bone walls.
      Both the base of the mandible and the inferior alveolar nerve were preserved. The
      patient is asymptomatic after 6 months of surgery. The age of the patient and the
      radiographic features were taken into account when deciding in favor of the
      conservative treatment.

PMID- 30237990
TI  - Autopsy in the elderly.

PMID- 30237991
TI  - Simultaneous living donor orthotopic renal transplantation and bilateral
      nephrectomy for recurrent renal cell carcinoma and renal failure: case report and
      review of literature.
AB  - Background: We report the case of a 43-year-old female patient with systemic
      lupus erythematosus, class III lupus nephritis, with predialysis creatinine
      levels around 350 MUmol/L (3.95 mg/dL) after partial resection of the left kidney
      with histologically verified papillary carcinoma in 2010. Preoperative computed
      tomography of the abdomen revealed a small 8 mm tumor in the left upper kidney
      pole. The patient was indicated for simultaneous bilateral nephrectomy and
      orthotopic renal transplantation with the aim to minimize invasiveness of the
      procedure as well as for curable tumor removal. Method: The procedure was
      performed under the full anesthesia trough upper middle laparotomy. As the first
      step, bilateral transperitoneal nephrectomy was performed. The live donor surgery
      started in a parallel theater to shorten the cold ischemic time of the graft. The
      renal graft had singe vessels and ureter; it was placed into the recipient's
      right orthotopic position. End-to-end anastomosis of the right renal vein and
      artery anastomosis were performed; ureter was anastomosed end-to-end using
      recipient's ureter. Results: The postoperative period was uneventful with
      repeatedly excellent ultrasonography check-up of the graft's perfusion. The
      patient was discharged after 13 days with a good renal function of the graft
      (urea: 15 mmol/L, creatinine 160 MUmol/L [1.80 mg/dL]). Conclusion: Orthotopic
      renal transplantation is a technically challenging but valid alternative for
      patients who are unsuitable candidates for heterotopic renal transplantation or
      in cases where there is a clear benefit of orthotopic renal transplantation.

PMID- 30237992
TI  - Treatment of Osteoporosis: Unmet Needs and Emerging Solutions.
AB  - Efficient therapies are available for the treatment of osteoporosis, however,
      there are still unmet needs. Anti-resorptive therapies only increase bone mineral
      density to a certain extent and reduce the risk of non-vertebral fractures by
      20%, only one anabolic option is available in most parts of the world-the effect
      of which levels off over time, and the evidence for combination therapy targeting
      both resorption and formation is limited. In addition, identification and
      treatment of patients with high and imminent fracture risk following a recent
      fracture and long-term adherence to treatment are 2 other very prominent
      challenges to the management of osteoporosis. The current review will focus on
      emerging osteoporosis treatments and optimized use of the existing treatments
      that may help overcome the currently unmet needs in the management of
      osteoporosis.

PMID- 30237993
TI  - Proton-pump Inhibitor Use and Fracture Risk: An Updated Systematic Review and
      Meta-analysis.
AB  - Background: This study's objective was to evaluate the association between proton
      pump inhibitor (PPI) use and bone fracture incidence and bone mineral density
      (BMD) by meta-analyzing the estimates reported by epidemiological and cohort
      studies. Methods: Data were acquired from studies identified after a literature
      search in electronic databases. Odds ratios (ORs), hazard ratios (HRs), and risk
      ratios (RRs) between PPI use and bone fracture incidence were pooled under the
      random effects model, and meta-analysis of standardized mean differences between
      PPI users and controls in cross-sectional values and BMD changes was conducted.
      Results: Thirty-three studies fulfilled the eligibility criteria. These studies
      provided data from 2,714,502 individuals with a mean age of 66.91 years (95%
      confidence interval [CI], 63.37-70.46); 33.21% (95% CI, 30.44-35.99) were males
      and 64.61% (95% CI, 60.73-68.49) were females. Overall, fracture incidence was
      22.04% (95% CI, 16.10-27.97) in PPI users and 15.57% (95% CI, 12.28-18.86) in
      controls. The overall effect size of the point estimate was 1.28 (95% CI, 1.22
      1.35) between PPI use and bone fracture incidence. There was a trend towards
      increased fracture incidence from short duration use: OR 1.29 (95% CI, 1.19
      1.40), medium duration use: OR 1.33 (95% CI, 1.12-1.55) and long duration use: OR
      1.62 (95% CI, 1.33-1.90). There was no significant difference in the standardized
      mean differences between PPI users and controls, either in cross-sectional BMD
      values or in the BMD change observed in longitudinal studies. Conclusions:
      Pooling of ORs, HRs, and RRs suggested that PPI use might increase fracture risk.
      However, there was no effect of PPI use on BMD.

PMID- 30237994
TI  - Linkage of Fibroblast Growth Factor 23 and Phosphate in Serum: Phosphate and
      Fibroblast Growth Factor 23 Reduction by Increasing Dose of Sevelamer.
AB  - Background: High serum phosphate and fibroblast growth factor-23 (FGF-23) levels
      are well-recognized independent risk factors of mortality and morbidity in
      patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating
      agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes.
      This study aimed to determine the best dose at which sevelamer could successfully
      reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD.
      Methods: CKD was induced using adenine. Healthy and CKD-induced rats were divided
      into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%,
      2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer.
      Biochemical factors and serum FGF-23 levels were measured using spectrophotometry
      and enzyme-linked immunosorbent assay methods. Results: Serum phosphate levels
      were best decreased in rats receiving 3% sevelamer in their diet (5.91+/-1.48
      mg/dL vs. 8.09+/-1.70 mg/dL, P<0.05) compared with the CKD control rats. A dose
      dependent decrease in serum FGF-23 levels was observed, and the most significant
      results were obtained in rats receiving 3% sevelamer compared with the CKD
      control rats (142.60+/-83.95 pg/mL vs. 297.15+/-131.10 pg/mL, P<0.01).
      Conclusions: Higher sevelamer doses significantly reduced serum phosphate and FGF
      23 levels in adenine-induced CKD rats.

PMID- 30237995
TI  - Maintenance Dose of Vitamin D: How Much Is Enough?
AB  - Background: It is still unclear the ideal vitamin D dosage once the deficiency
      and insufficiency is treated. Once deficiency was corrected we prospectively
      treated patients with 2,000 IU of vitamin D3 to check whether this dosage is
      enough to keep them above the 30 ng/mL of 25-hydroxy-vitamin D (25[OH]D).
      Methods: One hundred and thirty-five Saudi Arabian men and women treatment naive
      for the vitamin D deficiency and insufficiency were part of this study. History
      and clinical examination were done to rule out any metabolic bone disease. Weight
      and height was taken to calculate the body mass index (BMI). Patients who were
      vitamin D deficient (>=30 ng/mL), a standard treatment of 50,000 IU of vitamin D3
      weekly for 3 months, a blood test for the vitamin D levels at the end of 3
      months, maintenance dose of 2,000 IU of vitamin D3 for 3 months and a third blood
      sample after 3 months. Results: The data for 128 patients was available for
      analysis. The average age was 44.95+/-12.97 years with the mean BMI of 29.60+/
      2.59 kg/m2. The baseline 25(OH)D level was 13.16+/-3.30 ng/mL. The increase in
      the level of 25(OH)D on 50,000 IU weekly was significant from 13.16+/-3.3 ng/mL
      to 36.97+/-4.67 ng/mL (P<0.001) and then 2,000 IU daily for next 3 months, the
      level of 25(OH)D dropped top 20.38+/-5.42 ng/mL (P<0.001). Conclusions: Our study
      indicates that the maintenance dose of 2,000 IU of vitamin D is not enough for
      patients to keep the 25(OH)D levels above 30 ng/mL.

PMID- 30237996
TI  - Dental Panoramic Radiographic Indices as a Predictor of Osteoporosis in
      Postmenopausal Saudi Women.
AB  - Background: Many oral presentations of osteoporosis-a bone metabolic disease-were
      recorded. Thus, we aimed to assess panoramic radiomorphometric indices with bone
      mineral density (BMD) values among Saudi postmenopausal women and its importance
      in the prediction of osteoporosis. Methods: A total of 431 Saudi women were
      enrolled in this study. Panoramic radiographs were obtained at the time of BMD
      measurement. Subjects were fatherly classified into; normal BMD, osteopenia, and
      osteoporosis groups. Serum follicle-stimulating hormone, luteinizing hormone
      (LH), estradiol (E2), 25-hydroxy-vitamin D (25[OH]D) and intact-parathyroid
      hormone were measured. Moreover, serum creatinine, calcium, and phosphate,
      together with serum osteocalcin (s-OC), procollagen type I N-terminal propeptide
      (s-PINP) and cross-linked C-terminal telopeptide of type 1 collagen (s-CTX) were
      measured. Receiver-operator curve (ROC) curve analysis for use of mandibular
      cortical width (MCW), panoramic mandibular index (PMI), and maxillary-mandibular
      ratio (M/M ratio) to differentiate women with osteoporosis or osteopenia from
      normal subjects was calculated. Cut off values of 4.6 at T score <-1 and 4.1 at T
      score <=-2.5 were used. Results: Body mass index is significantly low in the
      osteoporotic group. There is no significant difference in serum levels of LH, E2,
      calcium, phosphate, and 25(OH)D between the studied groups. Moreover, s-OC, C
      terminal propeptide of procollagen type I, s-PINP, s-CTX, and urinary-CTX are
      significantly higher in osteoporosis than normal and osteopenia groups. ROC curve
      analysis revealed that MCW and PMI showed significant data while M/M ratio is non
      significant. Conclusions: It could be concluded that MCW as an important
      panoramic radiographic parameter can be used for prediction and diagnosis of
      osteoporosis in postmenopausal Saudi women with low BMD.

PMID- 30237997
TI  - Regional Distribution of Stress on the Distal Femur in Advanced Osteoarthritis.
AB  - Background: The aim of this study was to analyze regional differences in the
      stress distribution within the distal femur in advanced osteoarthritis (OA).
      Methods: Distal femoral specimens with primary OA were obtained from 10 female
      donor cadavers (mean age, 65 years; range, 53-79). As controls, distal femurs
      without OA were obtained from 10 age- and sex-matched female cadavers (mean age,
      67 years; range, 58-81). The articular surface of the distal femur was divided
      into anterior, middle, and posterior regions on each condyle. Mechanical
      properties and microstructure were assessed for each region with micro-computed
      tomography and finite element model analysis. Results: The control group showed
      differences in stress distribution among 6 regions on the distal femur (P=0.037),
      but there was no regional difference in stress distribution among 6 regions on
      the distal femur in the advanced OA group (P=0.179). Conclusions: Regional stress
      distribution in the distal femur was different between advanced OA and normal
      groups. There were no regional differences in stress distribution in the advanced
      OA group. Altered loading patterns, bone remodeling, and chemical composition
      will affect stress distribution.

PMID- 30237998
TI  - Relationship between Bone Density, Eating Habit, and Nutritional Intake in
      College Students.
AB  - Background: The importance of bone health is emphasized throughout the life
      cycle. Young adults have problems with bone health due to irregular lifestyle and
      unbalanced diet, but studies related to them are insufficient. The purpose of
      this study was to measure the bone mineral density (BMD) of college students and
      to analyze the differences in BMD according to lifestyle. Methods: BMD was
      measured by bone ultrasound in 161 male and female college students. The
      questionnaire was surveyed about lifestyle, eating habits, and nutrient intake
      status. Results: Osteopenia was 8.8% in male and 10.8% in female. The body fat
      percentage of female was significantly higher than male. Male college students,
      smoking, fast food consumption, and overeating rate were significantly higher
      than female. Nutrient intake was not significantly different between male and
      female students. But energy and vitamin A and C levels were inadequate, and
      protein and sodium intake was excessive compared with the recommended nutrient
      intake for Koreans. BMD was significantly lowest in male who often intake fast
      food than male who did not intake at all or intake sometimes. Female who often
      intake fast food had significantly lower BMD than female who did not eat at all.
      Conclusions: College students have different BMDs according to lifestyle. There
      was a difference in BMD according to smoking and fast food consumption.

PMID- 30237999
TI  - Association between Sarcopenia, Sarcopenic Obesity, and Chronic Disease in Korean
      Elderly.
AB  - Background: It is a very important social issue for Korea to have a healthy old
      age as an aged society. Aging causes a lot of physical changes, especially
      sarcopenia. Sarcopenia is defined as a persistent decrease in skeletal muscle and
      muscle strength. Sarcopenic obesity is a phenomenon in which fat is replaced
      instead of muscle. The purpose of this study was to examine the prevalence of
      sarcopenia and sarcopenic obesity in Korean elderly and to analyze the
      relationship with chronic disease. Methods: Data from the 2008 to 2011 the Korea
      National Health and Nutrition Survey were used. A total of 3,492 patients were
      classified into 3 groups (non-sarcopenia, sarcopenia, sarcopenic obesity), and
      general, anthropometry, health behavior, nutrient intake and chronic disease
      status were compared by the statistical analysis. Results: The rate of moderate
      exercise was significantly lower in the sarcopenia and sarcopenic-obesity group
      than in the non-sarcopenia group (P=0.007). The sarcopenic obesity group had
      significantly higher energy (P=0.005), protein (P=0.046) and fat (P=0.001) intake
      than the sarcopenic group. The sarcopenic-obesity group had the highest ratio of
      diabetes (P=0.023) and dyslipidemia (P=0.004) in the 3 groups. Compared with the
      non-sarcopenia group, in the sarcopenia and sarcopenic obesity groups, the odds
      ratios (ORs) of diabetes was increased by 1.24 and 2.16 while the ORs of
      dyslipidemia was increased by 1.12 and 1.50, respectively. Conclusions: Regular
      exercise and adequate nutrient intake (energy, protein and fat) are essential for
      the prevention of sarcopenia in Korean elderly, and management of chronic disease
      in sarcopenic obesity elderly is important.

PMID- 30238000
TI  - Reduced Handgrip Strength in Congenital Heart Disease With Regard to the Shunt
      Procedure in Infancy.
AB  - Objective: In many patients with congenital heart disease (CHD) arterial blood
      flow to the arms is inhibited due to shunt surgery in infancy. This study
      investigates the handgrip strength of patients with CHD in regard to previous
      shunt procedures. Patients and Methods: Handgrip was evaluated in 424 patients
      with various CHD (189 female, age 28.1 +/- 13.4 years) including 63 with shunt
      procedures in infancy; and 123 controls (51 female, 35.6 +/- 14.2 years) using a
      Jamar dynamometer adjusted for hand size. The best of three repetitions was
      recorded for each side and the right-to-left hand ratio was calculated. The 63
      shunted patients were grouped considering the side of the shunt: 14 right, 35
      central and 14 left. Results: Patients with CHD, especially shunts, had
      significantly lower handgrip strength in the dominant hand than controls
      (controls: 43.2 +/- 14.8 kg, CHD: 36.8 +/- 14.8 kg, left shunt: 33.6 +/- 14.6 kg,
      central shunt: 30.7 +/- 15.2 kg and right shunt 27.8 +/- 13.6 kg; p < 0.001). In
      controls the right hand was 8.3% stronger, comparable to patients with either no
      shunt or central shunt (controls: 8.3 +/- 13.2%; no shunt: 7.9 +/- 15.3%; central
      shunt: 9.5 +/- 18.1% p = 0.820). In patients with a left shunt the right hand was
      22.5 +/- 17.8% stronger than the left (p = 0.027 compared to central) while in
      those with a right shunt the right hand was 2.3 +/- 18.3% weaker (p = 0.049
      compared to central). Conclusions: Shunt procedures in infancy cause reduced
      handgrip strength in adulthood and diminished handgrip strength of the
      ipsilateral site.

PMID- 30238002
TI  - Exploitation of the Ugi 5-Center-4-Component Reaction (U-5C-4CR) for the
      Generation of Diverse Libraries of Polycyclic (Spiro)Compounds.
AB  - An Ugi multicomponent reaction with chiral cyclic amino acids, benzyl isocyanide
      and cyclic ketones (or acetone) has been exploited as key step for the generation
      of peptidomimetics. After a straightforward set of elaborations, the
      peptidomimetics were converted into polycyclic scaffolds displaying two
      orthogonally protected secondary amines. Libraries of compounds were obtained
      decorating the molecules through acylation/reductive amination reactions on these
      functional groups.

PMID- 30238001
TI  - "Losing the Phobia:" Understanding How HIV Pre-exposure Prophylaxis Facilitates
      Bridging the Serodivide Among Men Who Have Sex With Men.
AB  - The use of HIV serostatus information has played a pivotal role in partner
      selection norms. A phenomenon known as serosorting is the practice of selecting a
      partner based on a perception that they are of the same HIV status in order to
      avoid transmission from one partner to the other. An understudied aspect of
      serosorting is that it has a divisive effect-one accepts or rejects a potential
      partner based on a singular characteristic, the partner's HIV status, and thus
      excludes all others. This division has been formally referred to as the HIV
      serodivide. In this study, we explored partner selection strategies among a group
      of HIV-negative, young men who have sex with men (n = 29) enrolled in a PrEP
      demonstration project in Northern California. We found that trends in serosorting
      were in fact shifting, and that a new and opposite phenomenon was emerging,
      something we labeled "seromixing" and that PrEP use played a part in why norms
      were changing. We present three orientations in this regard: (1) maintaining the
      phobia: in which men justified the continued vigilance and exclusion of people
      living with HIV as viable sex or romantic partners, (2) loosening/relaxation of
      phobia: among men who were reflecting on their stance on serosorting and its
      implications for future sexual and/or romantic partnerships, and (3) losing the
      phobia: among men letting go of serosorting practices and reducing sentiments of
      HIV-related stigma. The majority of participants spoke of changing or changed
      attitudes about intentionally accepting rather than rejecting a person living
      with HIV as a sex partner. For those who maintained strict serosorting practices,
      their understandings of HIV risk were not erased as a result of PrEP use. These
      overarching themes help explain how PrEP use is contributing to a closing of the
      HIV serodivide.

PMID- 30238003
TI  - Effective Removal of Sulfanilic Acid From Water Using a Low-Pressure
      Electrochemical RuO2-TiO2@Ti/PVDF Composite Membrane.
AB  - Removal of sulfanilic acid (SA) from water is an urgent but still challenging
      task. Herein, we developed a low pressure electrochemical membrane filtration
      (EMF) system for SA decontamination using RuO2-TiO2@Ti/PVDF composite membrane to
      serve as not only a filter but also an anode. Results showed that efficient
      removal of SA was achieved in this EMF system. At a charging voltage of 1.5 V and
      a electrolyte concentration of 15 mM, flow-through operation with a hydraulic
      retention time (HRT) of 2 h led to a high SA removal efficiency (80.4%), as
      expected from the improved contact reaction of this compound with ROS present at
      the anode surface. Cyclic voltammetry (CV) analysis indicated that the direct
      anodic oxidation played a minor role in SA degradation. Electron spin resonance
      (ESR) spectra demonstrated the production of *OH in the EMF system. Compared to
      the cathodic polarization, anodic generated ROS was more likely responsible for
      SA removal. Scavenging tests suggested that adsorbed *OH on the anode (>*OH)
      played a dominant role in SA degradation, while O2*- was an important
      intermediate oxidant which mediated the production of *OH. The calculated
      mineralization current efficiency (MCE) of the flow-through operated system 29.3%
      with this value much higher than that of the flow-by mode (5.1%). As a
      consequence, flow-through operation contributed to efficient oxidation of SA
      toward CO2 and nontoxic carboxylic acids accounting for 71.2% of initial C. These
      results demonstrate the potential of the EMF system to be used as an effective
      technology for water decontamination.

PMID- 30238004
TI  - EUPATI Guidance for Patient Involvement in Medicines Research and Development:
      Health Technology Assessment.
AB  - The main aim of health technology assessment (HTA) is to inform decision making
      by health care policy makers. It is a systematic process that evaluates the use
      of health technologies and generally involves a critical review of international
      evidence related to clinical effectiveness of the health technology vs. the best
      standard of care. It can also include an evaluation of cost effectiveness, and
      social and ethical impacts in the local health care system. The HTA process
      advises whether or not a health technology should be used, and if so, how it is
      best used and which patients are most likely to benefit from it. The importance
      of patient involvement in HTA is becoming widely recognized, for scientific and
      democratic reasons. The extent of patient involvement in HTA varies considerably
      across Europe. Commonly HTA is still focused on quantitative evidence to
      determine clinical and/or cost effectiveness, but the interest in understanding
      patients' experiences and preferences is increasing. Some HTA bodies provide
      support for participation in their processes, but again this varies widely across
      Europe. The involvement of patients in HTA is determined at the national and
      regional level, and is not subject to any European-wide legislation. The guidance
      text presented in this article was developed as part of the work of the European
      Patients' Academy on Therapeutic Innovation (EUPATI) and covers the interaction
      between HTA bodies and patients and their representatives when medicines are
      being assessed. Other EUPATI guidance documents relate to patient involvement in
      pharmaceutical industry-led research and development, ethics committees, and
      regulatory authorities. The guidance provides recommendations for activities to
      support patient involvement in HTA bodies and specific guidance for individual
      HTA processes. It seeks to improve patient involvement, using the outcomes of
      published research and consensus-building exercises. It also draws on good
      practice examples from individual HTA bodies. The guidance is not intended to be
      prescriptive and should be used according to specific circumstances, national
      legislation, or the unique needs of each interaction. This article represents the
      formal publication of the HTA guidance text with discussion about recent progress
      in, and continuing barriers to, patient involvement in HTA.

PMID- 30238005
TI  - New Insights Into the Long Non-coding RNA SRA: Physiological Functions and
      Mechanisms of Action.
AB  - Long non-coding RNAs (lncRNA) are emerging as new genetic/epigenetic regulators
      that can impact almost all physiological functions. Here, we focus on the long
      non-coding steroid receptor RNA activator (SRA), including new insights into its
      effects on gene expression, the cell cycle, and differentiation; how these relate
      to physiology and disease; and the mechanisms underlying these effects. We
      discuss how SRA acts as an RNA coactivator in nuclear receptor signaling; its
      effects on steroidogenesis, adipogenesis, and myocyte differentiation; the impact
      on breast and prostate cancer tumorigenesis; and, finally, its ability to
      modulate hepatic steatosis through several signaling pathways. Genome-wide
      analysis reveals that SRA regulates hundreds of target genes in adipocytes and
      breast cancer cells and binds to thousands of genomic sites in human pluripotent
      stem cells. Recent studies indicate that SRA acts as a molecular scaffold and
      forms networks with numerous coregulators and chromatin-modifying regulators in
      both activating and repressive complexes. We discuss how modifications to SRA's
      unique stem-loop secondary structure are important for SRA function, and
      highlight the various SRA isoforms and mutations that have clinical implications.
      Finally, we discuss the future directions for better understanding the molecular
      mechanisms of SRA action and how this might lead to new diagnostic and
      therapeutic approaches.

PMID- 30238006
TI  - Classification and Outcome Measures for Psoriatic Arthritis.
AB  - Psoriatic arthritis (PsA) is an inflammatory arthritis with multiple
      manifestations: peripheral/axial arthritis, enthesitis, dactylitis, psoriasis,
      and nail involvement. From having an agreed upon classification criteria in 2006,
      the assessment of PsA has advanced from uncertainties to development and
      validation of numerous specific outcome measures. The Group for Research and
      Assessment of Psoriasis and Psoriatic arthritis (GRAPPA) has spearheaded the
      development of a core domain set and is now working on a core outcome measurement
      set to standardize outcome measures for PsA, that will provide guidance for use
      of instruments in randomized controlled trials (RCTs) and longitudinal
      observational studies (LOS). This article summarizes and updates these work
      processes to improve assessment of this multisystem complex rheumatologic
      disease.

PMID- 30238008
TI  - Identifying and Resolving End of Session Cues in Substance Detection Canine
      Training.
AB  - When training and working a substance detection canine, a trained final response
      should be performed immediately upon recognition of odor (Generally, a 1-3 s
      window is preferred within our detection practices). Typical canine training
      places much emphasis on planning and setting up training scenarios to achieve
      specific objectives but not much consideration is given to how to end a training
      session. When the canine fails to maintain criteria, trainers are left trying to
      determine the cause of poor performance. One consideration often overlooked is a
      phenomenon called End of Session Cueing that may exist in detection training
      whereby a previously trained canine no longer responds to odor because it has
      taken on aversive association. This may be due to several factors associated with
      motivation. The sequence of events at the end of a session can be as equally
      important to maintain motivation for the task of scent detection in future
      sessions. This paper will identify and examine multiple factors associated with
      "End of Session Cues" in working dogs, how they may be responsible for poor final
      response performance and discuss potential strategies to address them.

PMID- 30238007
TI  - Ponatinib Activates an Inflammatory Response in Endothelial Cells via ERK5
      SUMOylation.
AB  - Ponatinib is a multi-targeted third generation tyrosine kinase inhibitor (TKI)
      used in the treatment of chronic myeloid leukemia (CML) patients harboring the
      Abelson (Abl)-breakpoint cluster region (Bcr) T315I mutation. In spite of having
      superb clinical efficacy, ponatinib triggers severe vascular adverse events
      (VAEs) that significantly limit its therapeutic potential. On vascular
      endothelial cells (ECs), ponatinib promotes EC dysfunction and apoptosis, and
      inhibits angiogenesis. Furthermore, ponatinib-mediated anti-angiogenic effect has
      been suggested to play a partial role in systemic and pulmonary hypertension via
      inhibition of vascular endothelial growth factor receptor 2 (VEGFR2). Even though
      ponatinib-associated VAEs are well documented, their etiology remains largely
      unknown, making it difficult to efficiently counteract treatment-related
      adversities. Therefore, a better understanding of the mechanisms by which
      ponatinib mediates VAEs is critical. In cultured human aortic ECs (HAECs) treated
      with ponatinib, we found an increase in nuclear factor NF-kB/p65 phosphorylation
      and NF-kB activity, inflammatory gene expression, cell permeability, and cell
      apoptosis. Mechanistically, ponatinib abolished extracellular signal-regulated
      kinase 5 (ERK5) transcriptional activity even under activation by its upstream
      kinase mitogen-activated protein kinase kinase 5alpha (CA-MEK5alpha). Ponatinib
      also diminished expression of ERK5 responsive genes such as Kruppel-like Factor
      2/4 (klf2/4) and eNOS. Because ERK5 SUMOylation counteracts its transcriptional
      activity, we examined the effect of ponatinib on ERK5 SUMOylation, and found that
      ERK5 SUMOylation is increased by ponatinib. We also found that ponatibib-mediated
      increased inflammatory gene expression and decreased anti-inflammatory gene
      expression were reversed when ERK5 SUMOylation was inhibited endogenously or
      exogenously. Overall, we propose a novel mechanism by which ponatinib up
      regulates endothelial ERK5 SUMOylation and shifts ECs to an inflammatory
      phenotype, disrupting vascular homeostasis.

PMID- 30238009
TI  - Social Learning in Horses-Fact or Fiction?
AB  - Prima facie, the acquisition of novel behaviors in animals through observation of
      conspecifics seems straightforward. There are, however, various mechanisms
      through which the behavior of animals can be altered from observing others. These
      mechanisms range from simple hard-wired contagious processes to genuine learning
      by observation, which differ fundamentally in cognitive complexity. They range
      from social facilitation and local enhancement to true social learning. The
      different learning mechanisms are the subject of this review, largely because
      research on learning by observation can be confounded by difficulties in
      interpretation owing to the looming possibility of associative learning infecting
      experimental results. While it is often assumed that horses are capable of
      acquiring new behavior through intra-species observation, research on social
      learning in horses includes a variety of studies some of which may overestimate
      the possession of higher mental abilities. Assuming such abilities in their
      absence can have welfare implications, e.g., isolating stereotypical horses on
      the assumption that these behaviors can be learned though observation by
      neighboring horses. This review summarizes the definitions and criteria for the
      various types of social transmission and social learning and reviews the current
      documentation for each type in horses with the aim of clarifying whether horses
      possess the ability to learn through true social learning. As social ungulates,
      horses evolved in open landscapes, exposed to predators and grazing most of the
      day. Being in close proximity to conspecifics may theoretically offer an
      opportunity to learn socially, however anti-predator vigilance and locating
      forage may not require the neural complexity of social learning. Given the
      significant energetic expense of brain tissue, it is likely that social
      facilitation and local enhancement may have been sufficient in the adaptation of
      equids to their niche. As a consequence, social learning abilities may be
      maladaptive in horses. Collectively, the review proposes a novel differentiation
      between social transmission (social facilitation, local, and stimulus
      enhancement) and social learning (goal emulation, imitation). Horses are
      undoubtedly sensitive to intra-species transfer of information but this transfer
      does not appear to satisfy the criteria for social learning, and thus there is no
      solid evidence for true social learning in horses.

PMID- 30238010
TI  - Association of Fasciola gigantica Co-infection With Bovine Tuberculosis Infection
      and Diagnosis in a Naturally Infected Cattle Population in Africa.
AB  - Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a major
      livestock and public health problem in both high and low-income countries. With
      the current absence of an effective vaccine, control in cattle populations is
      reliant on regular testing and removal of positive animals. However, surveillance
      and control are hampered by imperfect diagnostic tests that have poorly described
      properties in naturally infected populations. Recent research in cattle co
      infected with the temperate liver fluke, Fasciola hepatica, has raised concerns
      about the performance of the intradermal skin test in high fluke incidence areas.
      Further, recent studies of parasitic co-infections have demonstrated their impact
      on Th1 and Th2 responses, concurrent disease pathology and susceptibility to
      mycobacterial infections. Here we report for the first time the association of co
      infection with the tropical liver fluke, Fasciola gigantica, with the presence of
      bTB-like lesions and the IFN-gamma response in naturally infected African cattle.
      After adjusting for age and sex we observed a complex interaction between fluke
      status and breed. Fulani cattle had a higher risk of having bTB-like lesions than
      the mixed breed group. The risk of bTB-like lesions increased in the mixed breed
      group if they had concurrent evidence of fluke pathology but was less clear in
      the coinfected Fulani breed. Further, we observed a slight decline in the IFN
      gamma levels in fluke infected animals. Finally we explored factors associated
      with IFN-gamma false negative results compared to the presence of bTB-like
      lesions. Fulani cattle had a higher risk of having a false negative result
      compared to the mixed breed group. Further, the mixed breed cattle had an
      increased risk of being false negative if also co-infected with fluke.
      Interesting, as with the risk of bTB-like lesions, this association was less
      clear in the Fulani cattle with weak evidence of a slight decrease in risk of
      having a false negative test result when fluke pathology positive. This
      interesting interaction where different breeds appear to have different responses
      to co-infections is intriguing but further work is needed to confirm and
      understand more clearly the possible confounding effects of different other co
      infections not measured here, breed, management or exposure risks.

PMID- 30238012
TI  - Quantifying the impact of inhalational burns: a prospective study.
AB  - Background: Inhalational injury is a major cause of morbidity and mortality in
      burns patients. This study aims to analyse the clinical outcomes, complications
      and bacteriology of inhalational burn patients. Methods: A prospective study was
      done on consecutive admissions to Burn Department, Singapore General Hospital
      over 15 months from January 2015 to March 2016. Presence of inhalational injury,
      demographics, complications and outcomes was recorded. Diagnosis of inhalational
      injury was based on history, symptoms and nasoendoscopy. Diagnosis of acute
      respiratory distress syndrome (ARDS), acute kidney injury (AKI) and infective
      complications were according to the Berlin criteria, acute kidney injury network
      (AKIN) classification stage 2 and above and the American Burns Association
      guidelines. Results: Thirty-five patients (17.3%) had inhalational burns out of
      202 patients (63.4% male, 57.4% Chinese population). The average age was 43 +/-
      16.7 years (range 16-86), and percentage of total body surface area (%TBSA) was
      12.1 +/- 18.0 (range 0-88). In patients with inhalational injury, age was 38.9 +/
      17.2 years and %TBSA was 30.3 +/- 32.3. In patients without inhalational injury,
      age was 44.1 +/- 12.8  years and %TBSA was 8.3 +/- 9.59. Compared to patients
      with cutaneous injury alone, patients with inhalational burns had more surgeries
      (3 +/- 7.07 vs 1 +/- 1.54, p = 0.003), increased length of stay (21 days vs 8
      days, p = 0.004) and higher in-hospital mortality rate (17.1% vs 0.6%, p <
      0.001). Incidence of ARDS and AKI was 48.6% and 37.1%, respectively, compared to
      0.6% and 1.2% in the patients without inhalational injury (p < 0.001). Patients
      with inhalational injury had increased incidence of bacteraemia (31.4% vs 2.4%, p
      < 0.001), pneumonia (37.1% vs 1.2%, p < 0.001) and burn wound infection (51.4% vs
      25.1%, p = 0.004). Inhalational injury predicted AKI with an adjusted odds ratio
      (OR) of 17.43 (95% confidence interval (CI) 3.07-98.87, p < 0.001); ARDS, OR =
      106.71 (95% CI 12.73-894.53, p < 0.001) and pneumonia, OR = 13.87 (95% CI 2.32
      82.94, p = 0.004). Acinetobacter baumannii was the most frequently cultured
      bacteria in sputum, blood and tissue cultures with inhalational injury. Gram
      negative bacteria were predominantly cultured from tissue in patients with
      inhalational injury, whereas gram-positive bacteria were predominantly cultured
      from tissue in patients without inhalational injury. Conclusions: Inhalational
      injury accompanying burns significantly increases the length of stay, mortality
      and complications including AKI, ARDS, infection and sepsis.

PMID- 30238013
TI  - The Safety of a Far Medial Arthroscopic Portal for Anatomic Glenoid
      Reconstruction: A Cadaveric Study.
AB  - Background: An arthroscopic technique for anatomic glenoid reconstruction has
      been proposed for the treatment of glenohumeral bone loss in patients with
      recurrent shoulder instability. This technique is proposed as an alternative to
      open techniques as well as to the technically challenging arthroscopic Latarjet
      procedure. In arthroscopic anatomic glenoid reconstruction, a distal tibial
      allograft is inserted through a novel far medial portal, superior to the
      subscapularis tendon and lateral to the conjoint tendon. Purpose: To evaluate the
      safety of the far medial arthroscopic portal for anatomic glenoid reconstruction
      in a cadaveric study. Study Design: Descriptive laboratory study. Methods: Ten
      cadaveric shoulder specimens were dissected after inside-out medial arthroscopic
      portal insertion in the lateral decubitus position for arthroscopic anatomic
      glenoid reconstruction. A single observer performed 3 measurements on each
      specimen with a digital caliper (to the nearest 0.1 mm) from the medial portal to
      neurovascular structures, and the mean (+/-SD) and the range were calculated. The
      anthropometric data of the cadaveric specimens were also collected. Results: The
      mean distances between the far medial arthroscopic portal and sensitive anatomic
      structures were as follows: 50.79 +/- 13.69 mm from the musculocutaneous nerve,
      46.28 +/- 9.64 mm from the axillary nerve, 6.71 +/- 8.52 mm from the cephalic
      vein, and 48.52 +/- 7.22 mm from the subclavian artery and vein. The mean size of
      the medial arthroscopic portal was 25.60 mm. In all cases, the subscapularis
      muscle was intact. Conclusion: The far medial arthroscopic portal for anatomic
      glenoid reconstruction without a subscapularis split presents a minimal risk to
      most neurovascular structures during bony reconstruction of the glenoid surface
      in patients with anterior shoulder instability. The only anatomic structure at
      risk is the cephalic vein, while the axillary and musculocutaneous nerves are at
      a safe distance away from the portal, based on previous shoulder arthroscopic
      portal safety studies in the literature. Clinical Relevance: Arthroscopic
      anatomic glenoid reconstruction using a distal tibial allograft is increasing in
      popularity for the treatment of anterior shoulder instability with significant
      bone loss. Being a relatively new technique, the safety of it has yet to be
      established. This study aimed to demonstrate the safety of a new portal used for
      arthroscopic anatomic glenoid reconstruction.

PMID- 30238011
TI  - Organic Acids and Potential for Modifying the Avian Gastrointestinal Tract and
      Reducing Pathogens and Disease.
AB  - Recently, antibiotics have been withdrawn from some poultry diets; leaving the
      birds at risk for increased incidence of dysbacteriosis and disease. Furthermore,
      mortalities occurring from disease contribute between 10 to 20% of production
      cost in developed countries. Currently, numerous feed supplements are being
      proposed as effective antibiotic alternatives in poultry diets, such as
      prebiotics, probiotics, acidic compounds, competitive exclusion products, herbs,
      essential oils, and bacteriophages. However, acidic compounds consisting of
      organic acids show promise as antibiotic alternatives. Organic acids have
      demonstrated the capability to enhance poultry performance by altering the pH of
      the gastrointestinal tract (GIT) and consequently changing the composition of the
      microbiome. In addition, organic acids, by altering the composition of the
      microbiome, protect poultry from pH-sensitive pathogens. Protection is further
      provided to poultry by the ability of organic acids to potentially enhance the
      morphology and physiology of the GIT and the immune system. Thus, the objective
      of the current review is to provide an understanding of the effects organic acids
      have on the microbiome of poultry and the effect those changes have on the
      prevalence of pathogens and diseases in poultry. From data reviewed, it can be
      concluded that the efficacy of organic acids on shifting microbiome composition
      is limited to the time of administration, the composition of the organic acid
      product, and the current health conditions of poultry.

PMID- 30238014
TI  - Imaging-Based Prevalence of Superior Labral Anterior-Posterior Tears
      Significantly Increases in the Aging Shoulder.
AB  - Background: Superior labral anterior-posterior (SLAP) tears can be associated
      with pain and shoulder dysfunction. Relatively little is known about the age
      related prevalence of SLAP tears. Purpose: To investigate the age-related
      prevalence of imaging-diagnosed SLAP tears in a heterogeneous grouping of
      shoulder conditions in a large cohort at a single institution with multiple
      blinded reviewers. Study Design: Cross-sectional study; Level of evidence, 3.
      Methods: A total of 281 shoulder magnetic resonance imaging (MRI) scans obtained
      over 8 months were reviewed by a musculoskeletal radiologist and an orthopaedic
      surgeon. The mean +/- SD age of the group was 49.6 +/- 15.5 years, and 107 of the
      patients were female (38.1%). Patients were divided into 4 age groups: 35 years
      or younger, 36 to 50 years, 51 to 65 years, and older than 65 years. Statistical
      analyses were completed by use of the Fisher exact test to compare proportions of
      SLAP tears between age groups, odds ratios to determine the likelihood of having
      a SLAP tear in each age group, and a logistic regression to control for
      associated abnormalities. Results: There was a significant diffference in the
      proportion of SLAP tears found on the MRIs for each age group (P < .001).
      Patients were significantly more likely to have SLAP tears if aged 51 to 65 years
      (66.7%; odds ratio [OR], 2.00; 95% CI, 1.27-3.15) and if older than 65 years
      (81.2%; OR, 4.31; 95% CI, 2.36-7.88). No increased prevalence was observed in
      patients aged 35 years or younger (47.5%; OR, 0.91; 95% CI, 0.55-1.50) or 36 to
      50 years (51.8%; OR, 1.08; 95% CI, 0.70-1.67). Logistic regression demonstrated
      that age was the only significant predictor for having a SLAP tear (P < .001).
      Kappa values were 0.46 to 0.65 between reviewers, indicating moderate to
      substantial agreement. Conclusion: An increasing prevalence of MRI-based SLAP
      tears was observed with increasing patient age. Patients older than 50 years were
      significantly more likely to have superior labral abnormalities regardless of
      other shoulder injury or disease.

PMID- 30238017
TI  - Elongated Styloid Processes of the Temporal Bone as a Cause of Dysphagia.

PMID- 30238015
TI  - Choriocapillaris changes in dry age-related macular degeneration and geographic
      atrophy: a review.
AB  - Age-related macular degeneration (AMD) is a leading cause of central vision loss
      worldwide. The progression of dry AMD from early to intermediate stages is
      primarily characterized by increasing drusen formation and adverse impact on
      outer retinal cells. Late stage AMD consists of either geographic atrophy (GA),
      the non-exudative (dry) AMD subtype, or choroidal neovascularization, the
      exudative (wet) AMD subtype. GA is characterized by outer retinal and choroidal
      atrophy, specifically the photoreceptor layer, RPE, and choriocapillaris. Much
      remains to be discovered regarding the pathogenesis of AMD progression and
      subsequent development of GA. As the functionality of all three layers is closely
      linked, the temporal sequence of events that end up in atrophy is important in
      the understanding of the pathogenic pathway of the disease. The advent of OCTA,
      and particularly of swept-source technology, has allowed for depth-resolved
      imaging of retinal vasculature and the choriocapillaris. With the use of OCTA,
      recent studies demonstrate that choriocapillaris flow alterations are closely
      associated with the development and progression of AMD. Such changes may even
      possibly offer predictive value in determining progression of GA. This article
      reviews studies demonstrating choriocapillaris changes in dry AMD and summarizes
      the existing literature on the potential role of the choriocapillaris as a key
      factor in the pathogenesis of AMD.

PMID- 30238018
TI  - Solitary Extrahepatic Intramuscular Metastasis from Cryptogenic Hepatocellular
      Carcinoma.
AB  - Although hepatocellular carcinoma (HCC) recurrence after curative resection is
      not uncommon, it primarily recurs in the liver prior to metastatic progression.
      We report a case of resected pT2N0 cryptogenic HCC that recurred in the superior
      paracervical musculature without evident intrahepatic recurrence. The patient
      also developed cervical spine instability requiring urgent neurosurgery.
      Cryptogenic HCC is thought to arise from non-alcoholic fatty liver disease even
      without cirrhosis. Unfortunately, it also portends a worse prognosis compared to
      HCC of other etiologies. This highlights the aggressive behavior of cryptogenic
      HCC, which warrants further research as non-alcoholic fatty liver disease becomes
      increasingly common.

PMID- 30238016
TI  - Bowman layer transplantation in the treatment of keratoconus.
AB  - Several treatment options corresponding to the grade of keratoconus have been
      established. These are ultra-violet corneal crosslinking and intracorneal ring
      segments for mild to moderate keratoconus, and penetrating keratoplasty or deep
      anterior lamellar keratoplasty for the more advanced cases of keratoconus. Bowman
      layer transplantation was developed as a procedure for patients with advanced,
      progressive keratoconus. The technique consists of transplanting an isolated
      donor Bowman layer into a mid-stromal pocket of a keratoconic cornea resulting in
      corneal flattening and stabilization against further ectasia. Thus, it aims at
      corneal stabilization in eyes with advanced keratoconus, and enabling continued
      contact lens wear for normal visual functionality. By being a sutureless
      procedure and using an acellular graft, it potentially avoids commonly known
      suture and graft-related complications of penetrating or deep anterior lamellar
      keratoplasty. The treatment seems to be a promising option in the management of
      advanced keratoconus in order to postpone or prevent a more invasive corneal
      surgery, while minimizing the risk of complications and allowing less stringent
      surveillance and less intensive medical therapy.

PMID- 30238019
TI  - A Second Attack of Anisakis: Intestinal Anisakiasis Following Gastric
      Anisakiasis.
AB  - A 50-year-old man presented with epigastric pain after eating raw mackerel.
      Abdominal computed tomography revealed submucosal edema of the gastric antrum and
      pelvic ileum. Gastroscopy revealed an Anisakis simplex in the gastric antrum. His
      epigastric pain resolved after endoscopic removal of the Anisakis; however, he
      developed right lower quadrant pain the following day. Abdominal computed
      tomography showed submucosal edema of the terminal ileum involving different
      ileal loops, which was not present on admission. The patient developed delayed
      intestinal anisakiasis. A serving of raw fish may contain more than one Anisakis.
      After gastric anisakiasis, a second Anisakis may cause intestinal anisakiasis.

PMID- 30238020
TI  - Conceptual relations compete during auditory and visual compound word
      recognition.
AB  - Previous research has shown that compound word recognition involves selecting a
      relational meaning (e.g., 'box for letters' for letterbox) out of a set of
      competing relational meanings for the same compound. We conducted five
      experiments to investigate the role of competition between relational meanings
      across visual and auditory compound word processing. In Experiment 1 conceptual
      relations judgments were collected for 604 English compound words. From this
      database we computed an information-theoretic measure of competition between
      conceptual relations - entropy of conceptual relations. Experiments 2 and 3
      report that greater entropy (i.e., increased competition) among a set of
      conceptual relations leads to longer latencies for compounds in auditory lexical
      decision. Experiments 4 and 5 demonstrate the same result in two visual lexical
      decision studies. These findings provide evidence that relational meanings are
      constructed and evaluated during compound recognition, regardless of whether
      compounds are recognized via auditory or visual input.

PMID- 30238021
TI  - Array Designer: automated optimized array design for functional near-infrared
      spectroscopy.
AB  - The position of each source and detector "optode" on the scalp, and their
      relative separations, determines the sensitivity of each functional near-infrared
      spectroscopy (fNIRS) channel to the underlying cortex. As a result, selecting
      appropriate scalp locations for the available sources and detectors is critical
      to every fNIRS experiment. At present, it is standard practice for the user to
      undertake this task manually; to select what they believe are the best locations
      on the scalp to place their optodes so as to sample a given cortical region-of
      interest (ROI). This process is difficult, time-consuming, and highly subjective.
      Here, we propose a tool, Array Designer, that is able to automatically design
      optimized fNIRS arrays given a user-defined ROI and certain features of the
      available fNIRS device. Critically, the Array Designer methodology is
      generalizable and will be applicable to almost any subject population or fNIRS
      device. We describe and validate the algorithmic methodology that underpins Array
      Designer by running multiple simulations of array design problems in a realistic
      anatomical model. We believe that Array Designer has the potential to end the
      need for manual array design, and in doing so save researchers time, improve
      fNIRS data quality, and promote standardization across the field.

PMID- 30238022
TI  - E-cigarettes Warning Labels and Modified Risk Statements: Tests of Messages to
      Reduce Recreational Use.
AB  - Objectives: We tested how variations of the warning message on e-cigarette
      packages influenced risk and ambiguity perceptions, and whether including a
      modified risk statement on the package influenced how the warning label was
      perceived. Method: A 4 (warning text) * 2 (modified risk statement), plus
      control, experiment (N = 451) was conducted. Results: Smoking status, sex, and
      the language used in the warning statements interacted to influence risk
      perceptions. For example, non-smoking women perceived e-cigarettes with the FDA
      text at 30% of the package as riskier than the FDA text at 12-point type.
      Additionally, including a modified risk statement on the package increased
      ambiguity among non-smokers, as did an abstract warning label. Conclusions: When
      evaluating the effectiveness of warning label text, it is important to consider
      smoking status and sex. Additionally, including modified risk statements on the
      package with the warning label could potentially increase ambiguity among non
      smokers.

PMID- 30238024
TI  - Data on the volumes of water stored in the reservoirs supplying the Metropolitan
      Area of Sao Paulo (2003-2015).
AB  - The dataset addressed in this article relates to the research article entitled
      "Urban water supply and the changes in the precipitation patterns in the
      Metropolitan Area of Sao Paulo - Brazil" (Lima et al., 2018) [1]. The dataset
      presents the indices of water volumes stored in the reservoirs that supply water
      to the Metropolitan Area of Sao Paulo (MASP). These indices were calculated based
      upon data provided by the Basic Sanitation Company of the State of Sao Paulo
      (SABESP) as of the year 2003 (SABESP -Basic Sanitation Company of the State of
      Sao Paulo, 2017) [2]. These data include air temperature, evapotranspiration,
      total flow and daily withdrawal. However, due to issues related to information
      protection, SABESP only provides data on six of the eight water-producing systems
      that supply the MASP with water. Thus, the data available on the SABESP website
      each day were collected, processed and entered into this article calculation
      tables.

PMID- 30238025
TI  - A survey of sequences of KT-HAK-KUP transporters in green algae and basal land
      plants.
AB  - In this data article, information is provided on sequences of KT-HAK-KUP
      transporters from green algae and basal land plants. A data set is offered
      containing sequences corresponding to the chlorophyte algae Chlamydomonas
      eustigma, Gonium pectorale and Coccomyxa subellipsoidea, the charophyte algae
      Coleochaete orbicularis and Klebsormidium flaccidum, the bryophyte Sphagnum
      fallax, the marchantophyte Marchantia polymorpha and the gymnosperm Pinus taeda,
      which have been not formerly analyzed. In addition, an analysis of similarity
      scores among representatives of the clusters recognized in photosynthetic green
      organisms (namely, chlorophyte algae, charophyte algae, basal embryophytes and
      higher embryophytes) is performed as well as an analysis of membrane topology for
      them.

PMID- 30238026
TI  - Transcriptomic data on the role of PEST-domain-enriched tyrosine phosphatase in
      the regulation of antigen-mediated activation and antiallergic action of
      glucocorticoids in mast cells.
AB  - Protein tyrosine phosphatases and glucocorticoids are known to regulate allergic
      and antiallergic action in activated mast cells. Here we provide RNA sequencing
      and quantitative real-time PCR data from bone marrow derived mast cells, for wild
      type and PEST-domain-enriched tyrosine phosphatase (PEP) null mice, activated by
      immunoglobulin E sensitization and dinitrophenol treatment, and additionally
      treated with the glucocorticoid dexamethasone. The transcriptomics experiment was
      performed in duplicate with a total of 16 samples (GSE108972).

PMID- 30238027
TI  - The Dig It Check It model.
AB  - This data article describes how the Dig It Check It (DICI) model operates. The
      purpose of the DICI model is to assess the effectiveness of a specified
      subsurface sampling program in the detection of archaeological sites (Way and
      Tabrett, in press) [1]. Specifically, the aim of the model is to determine the
      inherent biases of the specified sampling program, i.e. what is the probability
      that sites of a certain size, density and density-distribution will be, or were,
      missed by the sampling program. A simulation is run which randomly places sites,
      the characteristics of which can be varied between runs, in a sampling area with
      the specified test-pit layout to determine the probability of overlap between the
      test-pits and sites with the selected characteristics. When overlap does occur,
      the site is recorded as intersected. The model then calculates the site density
      at that point and compares it with the test-pit size to determine whether the
      density is great enough for detection to also occur.

PMID- 30238028
TI  - Quantum Hall device data monitoring following encapsulating polymer deposition.
AB  - The information provided in this data article will cover the growth parameters
      for monolayer, epitaxial graphene, as well as how to verify the layer homogeneity
      by confocal laser scanning and optical microscopy. The characterization of the
      subsequently fabricated quantum Hall device is shown for example cases during a
      series of environmental exposures. Quantum Hall data acquired from a CYTOP
      encapsulation is also provided. Data from Raman spectroscopy, atomic force
      microscopy, and other electrical property trends are shown. Lastly, quantum Hall
      effect data are presented from devices with deposited Parylene C films measuring
      10.7 MUm and 720 nm. All data are relevant for Rigosi et al. [1].

PMID- 30238029
TI  - Plant functional trait data and reflectance spectra for 22 palmiet wetland
      species.
AB  - We provide reflectance spectra for 22 South African palmiet wetland species
      collected in spring 2015 from three wetlands throughout the Cape Floristic
      Region. In addition, we provide summarized plant functional trait data, as well
      as supporting and meta-data. Reflectance spectra were collected with a portable
      ASD Fieldspec Pro using standard methods. The 14 plant functional traits were
      measured on 10 replicates of each species, following standard protocols. We
      provide tables detailing these standard methods, as well a table with hypotheses
      on how these 14 continuous traits, as well as an additional 9 categorical traits,
      may affect ecosystem service provision. In addition, tables are attached which
      detail which functional and spectral groups these species belong to, according to
      the data. Finally, we include a photographic plate of the species data are
      provide for. We make these data available in an effort to assist in research on
      the understanding of how traits affect ecosystem service provision in wetlands,
      and particularly of whether remote sensing can be used to map these traits in
      wetlands.

PMID- 30238030
TI  - Effect of chemical modification of titanium dioxide surface with dicarboxylic
      acid on the crystalline parameters and rheology behavior in polypropylene
      composites.
AB  - In this document, we present the effect of the surface modification of titanium
      dioxide particles with dicarboxylic acid on the rheological behavior of isotactic
      polypropylene composites. In addition to evaluating the effect of this type of
      modified fillers on the crystalline parameters such as long period, crystalline
      thickness and amorphous thickness, comparing it with unmodified fillers and pure
      polymer.

PMID- 30238031
TI  - Experimental data on mechanical properties evaluation of medium carbon steel
      quenched in different waste media.
AB  - Several wastes can be instrumental in the improvement of the mechanical
      properties of medium carbon steel when quenched. The quenching media employed
      such as coconut water (CW), pap water (PW) and spent engine oil (SPE) have been
      largely considered as wastes. The data in this article are related to the
      research article titled "Mechanical Properties Improvement Evaluation of Medium
      Carbon Steels Quenched in Different Media" (Ikubanni et al., 2017) [1]. The
      article provides information on the mechanical properties evaluation of medium
      carbon steel quenched in different media. Twenty-seven (27) samples of medium
      carbon steel samples were heated to temperatures of 730  degrees C, 760  degrees
      C and 790  degrees C and soaked for 30, 45 and 60 min respectively. The test
      results recorded include hardness value, yield strength (YS) and the ultimate
      tensile strength (UTS) for each of the samples at different heating temperatures
      and soaking time for the different quenching media.

PMID- 30238032
TI  - Data survey on public-private professionals role in building control measures
      within the Nigerian construction industry.
AB  - The data survey focused on building control measures which are critical in
      attaining sustainable built environment. The data examined the public and private
      professional's performance of building control measures and its barriers in
      Lagos. The targets consist of sixty (60) construction experts in public and
      private construction firms operating in Lagos. The sample size was generated from
      the pool of registered construction professional's from private and public
      construction organizations in Lagos using random sampling technique. Descriptive
      statistics and inferential tests which include Kruskal-Wallis and Mann-Whitney U
      tests were performed on the dataset generated. The data harvested will avail the
      construction expert's in public and private construction industry on the need for
      partnership in a bid to enhance building control measures performance in Lagos.

PMID- 30238033
TI  - Prolonged DNA hydrolysis in water: A study on DNA stability.
AB  - This work provides a protocol for the in vitro production of damaged DNA samples.
      In particular, heat-mediated hydrolysis of the samples at 70  degrees C in
      ultrapure water was performed in 1.7 mL Eppendorf tubes sealed by Parafilm for 0
      36 h. The chemical/physical features of the resulting samples are described.
      After normalization of the qPCR data, these were compared with those obtained
      from samples treated for 0-10 h in a previous study.

PMID- 30238034
TI  - Detailed structure information a highly thermostable Tb-cluster that based on a
      prodrug ligand of 2,4,5-trifluoro-3-methoxybenzoic acid.
AB  - In this brief data article, we present the precise structural information, PARD
      data and thermographic analysis of the Tb-cluster. Detailed structure,
      luminescence and detecting properties were discussed in our previous study (Zhao
      et al., 2017) [1]. The data includes the coordination modes of ligand, PXRD
      patterns of these Ln-MOFs, thermostability, detailed bond lengths and bond angles
      of the Tb-cluster.

PMID- 30238035
TI  - Data for dynamics analysis of riverine dissolved organic in watersheds.
AB  - This data article presents water stage, flow, and net primary productivity (NPP)
      data that were used to analyze the dynamics of the riverine dissolved organic
      carbon (DOC) dynamics in the Rukarara River watershed in Rwanda. We measured
      water stage data every 15 min and calculated daily averages used to estimate flow
      based on rating curves. The rating curves were produced using several measured
      contemporaneous water stage and flow data. Estimated flow data were used to
      calculate water dissolved organic carbon (DOC) loadings separate the total stream
      flow into quick and baseflow. Annual NPP data for a 15-year period were used to
      estimate the effect of proportion of stream DOC loading on carbon sequestration
      within the Rukarara River watershed.

PMID- 30238036
TI  - Physical and chemical data of WS2 platelets and thickness-dependent
      photoresponses.
AB  - In this data article, the properties of WS2/ZnO type-I heterostructure which
      corresponds to the research article "Vertically trigonal WS2 layer embedded
      heterostructure for enhanced ultraviolet-visible photodetector" (Nguyen et al.,
      2018) are presented by characteristics of WS2 layer, diode properties, and
      thickness dependent photoresponses. The device performances under the effect of
      rapid thermal processing (RTP) is presented. The WS2 platelets grown by large
      area sputtering method (Nguyen et al., 2018) was characterized in term of
      morphology and chemical elements distribution by using transmission electron
      microscope (TEM), energy dispersive spectroscopy (EDS) and X-Ray photoelectron
      spectroscopy (XPS). Diode characterization of WS2/ZnO like rectifying ratio,
      ideal factor and barrier height are presented. The variation of photocurrent of
      ITO/WS2/ZnO/FTO/glass photodetector, its dependence on the WS2 thickness and
      influence of post- thermal treatment are presented.

PMID- 30238037
TI  - Data on the early oxidation of SiO2-coated pure Ti and bulk Ti5Si3 at 800 
      degrees C.
AB  - Oxidation of pure Ti sputtered with a 250 nm layer of amorphous SiO2 and bulk
      Ti5Si3 was conducted at 800  degrees C for 2 or 32 h in a 1 standard cubic
      centimeter per minute (SCCM) O2/4 SCCM Ar environment (approximately pO2 = 0.2
      atm/20.3 kPa). Specimens were characterized using transmission electron
      microscopy, scanning transmission electron microscopy, and energy dispersive
      spectroscopy. The data in this article accompanies research article "Early
      oxidation behavior of Si-coated titanium" [1], which contains further discussion.
      The data for this article is hosted at the Materials Commons data repository and
      is available for download at
      https://materialscommons.org/mcapp/#/data/dataset/b8bc8038-a735-4cb9-9a9e
      a0fb912b248c.

PMID- 30238038
TI  - Data on the estimating the risk of cancer due to some common radiographs in
      Tehran city.
AB  - The purpose of the data is to estimate the excessive risk of cancer due to some
      common radiographs in Tehran. The data were collected in 8 radiology centers in
      Tehran city and on 283 patients with eight radiographic views. To obtain the
      data, PCXMC 2.0 based on Monte Carlo calculations, has been used to calculate the
      effective dose of each organ, and annual effective dose. The effective dose,
      cumulative effective dose, number of radiographs per year and excessive cancer
      risk due to the type of radiographs calculated. The additional risk of lethal
      cancer resulting from these radiographs in the target population is about 14.81
      cases of the total population of Tehran city in one year.

PMID- 30238039
TI  - Observed data of extreme rainfall events over the West African Sahel.
AB  - The data described in this article are sets of daily rainfall values derived from
      observed station records. The data was recorded by 72 in-situ rain gauges spread
      over the West African Sahel. The daily rainfall time series from synoptic,
      climate, agro-meteorological, and rainfall stations are assessed for quality and
      consistency before extreme values are extracted based on 90th, 95th, and 99th
      percentile thresholds. This data is free for use as part of the study "Scales for
      rating heavy rainfall events in West African Sahel" [1] (Salack et al., 2018).
      Complementary and up to date time series can be taken from WASCAL data
      infrastructure (WADI) geoportal https://wascal
      dataportal.org/wascal_searchportal2/. This is a derived product (DP), made public
      in line with WASCAL's "3rd party data sharing policy" signed by the WASCAL member
      countries.

PMID- 30238023
TI  - Anti-stress neuropharmacological mechanisms and targets for addiction treatment:
      A translational framework.
AB  - Stress-related substance use is a major challenge for treating substance use
      disorders. This selective review focuses on emerging pharmacotherapies with
      potential for reducing stress-potentiated seeking and consumption of nicotine,
      alcohol, marijuana, cocaine, and opioids (i.e., key phenotypes for the most
      commonly abused substances). I evaluate neuropharmacological mechanisms in
      experimental models of drug-maintenance and relapse, which translate more readily
      to individuals presenting for treatment (who have initiated and progressed). An
      affective/motivational systems model (three dimensions: valence, arousal,
      control) is mapped onto a systems biology of addiction approach for addressing
      this problem. Based on quality of evidence to date, promising first-tier
      neurochemical receptor targets include: noradrenergic (alpha1 and beta
      antagonist, alpha2 agonist), kappa-opioid antagonist, nociceptin antagonist,
      orexin-1 antagonist, and endocannabinoid modulation (e.g., cannabidiol, FAAH
      inhibition); second-tier candidates may include corticotropin releasing factor-1
      antagonists, serotonergic agents (e.g., 5-HT reuptake inhibitors, 5-HT3
      antagonists), glutamatergic agents (e.g., mGluR2/3 agonist/positive allosteric
      modulator, mGluR5 antagonist/negative allosteric modulator), GABA-promoters
      (e.g., pregabalin, tiagabine), vasopressin 1b antagonist, NK-1 antagonist, and
      PPAR-gamma agonist (e.g., pioglitazone). To address affective/motivational
      mechanisms of stress-related substance use, it may be advisable to combine agents
      with actions at complementary targets for greater efficacy but systematic studies
      are lacking except for interactions with the noradrenergic system. I note
      clinically-relevant factors that could mediate/moderate the efficacy of anti
      stress therapeutics and identify research gaps that should be pursued. Finally,
      progress in developing anti-stress medications will depend on use of reliable CNS
      biomarkers to validate exposure-response relationships.

PMID- 30238041
TI  - Data on quantification of PAHs and elemental content in dry Camellia sinensis and
      herbal tea.
AB  - Here we present data on potentially toxic metals and polycyclic aromatic
      hydrocarbons (PAHs) in commercially sold tea brands in Nigeria. The article
      provides data on the sequential extraction and the pseudo-total concentrations of
      eight metals (Cd, Cr, Cu, Mn, Ni, Pb, V and Zn) and polycyclic aromatic
      hydrocarbons (PAHs) in dry Camellia sinensis and herbal tea. The three-step
      Community Bureau of Reference (BCR) method and acid digestion with aqua regia
      were adopted for sequential and total metal extractions, respectively. The
      extraction of branded tea samples for PAHs analysis has been described in
      "Concentrations, sources and risk characterisation of polycyclic aromatic
      hydrocarbons (PAHs) in green, herbal and black tea products in Nigeria" [1] and
      "Polycyclic Aromatic Hydrocarbons (PAHs) Occurrence and Toxicity in C. sinensis
      and Herbal Tea" [2]. Elemental and PAHs analyses of extracts were determined by
      Microwave Plasma Atomic Emission Spectroscopy (Agilent MP-AES 4100) and Agilent
      gas chromatograph 7890A coupled with flame ionization detector (FID),
      respectively.

PMID- 30238040
TI  - Data for rate versus rhythm control strategy on stroke and mortality in patients
      with atrial fibrillation.
AB  - The data relates to the cohort of patients with atrial fibrillation (AF) from the
      National Health Insurance Research Database of Taiwan, "Rhythm Control Better
      Prevents Stroke and Mortality than Rate Control Strategies in Patients with
      Atrial Fibrillation - A Nationwide Cohort Study" (Weng et al., in press). The AF
      patients might receive either rate or rhythm control strategy according to the
      medication used. The baseline medication in rate and rhythm control groups was
      included in this dataset. Multivariate Cox hazards regression model was used to
      evaluate the hazard ratio (HR) for major adverse cardiovascular events (MACE),
      including ischemic/hemorrhagic stroke and mortality in AF patients receiving rate
      or rhythm control. The occurrence of MACE was identified from the ICD-9 CM codes.
      The data also contains the HR for MACE stratified by the CHA2DS2-VASc score,
      baseline characteristics, and the duration of strategy employed of the AF
      patients.

PMID- 30238042
TI  - A dataset of temperature and salinity in the South Brazil Bight: Identifying
      water mass interfaces.
AB  - Temperature and salinity data were recorded at the slope and outer shelf of the
      South Brazil Bight, from November 2014 to February 2015 using an Underwater
      Autonomous Vehicle, specifically, a glider. During the mission, the slope was
      crossed 10 times, reaching depths of up to 970 m and with a sampling rate of one
      record per second. The density profiles were also calculated to estimate
      interface levels between Tropical Water (TW) and South Atlantic Central Water
      (SACW), and between SACW and Antarctic Intermediate Water (AAIW). The interface
      levels are presented in cross section figures and the raw dataset is provided in
      netCDF files, including scientific and navigation datasets.

PMID- 30238043
TI  - Dataset on mice body weights and food intake following treatment with PG545.
AB  - This data article contains analysis of data observed in E0 mice placed on high
      fat diet, and treated by intraperitoneal injections of either normal saline
      (control) or the heparanase inhibitor PG545, in two different doses. Mice body
      weights and food intake were measured weekly and analyzed data are presented in
      graphs. Data will be of value for further understanding the role of the enzyme
      heparanase in controlling food intake and body weight. For further
      interpretations, see please "Heparanase inhibition attenuates atherosclerosis
      progression and liver steatosis in E0 mice" (Muhammad et al. 2018).

PMID- 30238044
TI  - Erratum: Removal notice.
AB  - [This corrects the article DOI: 10.1016/j.jdcr.2017.10.004.].

PMID- 30238045
TI  - Group C streptococcal cellulitis, looking deeper than the skin.

PMID- 30238046
TI  - Madelung lipomatosis presenting as a manifestation of myoclonic epilepsy with
      ragged red fibers (MERRF) syndrome.

PMID- 30238047
TI  - Rare presentation of erythema elevatum diutinum.

PMID- 30238048
TI  - Treatment of psoriasis vulgaris using low-dose naltrexone.

PMID- 30238049
TI  - Persistent injection site nodules from exenatide: Successful treatment with
      intralesional triamcinolone.

PMID- 30238050
TI  - Certolizumab in a patient with severe psoriasis and concomitant hepatitis C virus
      infection.

PMID- 30238051
TI  - Dermoscopy of eccrine angiomatous hamartoma: The spitzoid pattern.

PMID- 30238052
TI  - 55-year-old man with ulcers in inguinal fold and intergluteal cleft found to have
      systemic Langerhans cell histiocytosis.

PMID- 30238053
TI  - Retraction notice.
AB  - [This retracts the article DOI: 10.1016/j.jdcr.2017.10.009.].

PMID- 30238054
TI  - Parental education differentially predicts young adults' frequency and quantity
      of alcohol use in a longitudinal Swedish sample.
AB  - Background: Alcohol consumption contributes to health inequalities, but few
      studies have examined how socially differentiated alcohol use develops across the
      life course. In this study, we examine how one aspect of childhood socioeconomic
      position (parental education) relates to two often-conflated young adult drinking
      patterns: drinking frequency and quantity per occasion. Using a life course
      perspective, we also explore whether parental drinking patterns or young adults'
      own educational attainment might account for such associations. Methods: This
      study used longitudinal data from the nationally representative Swedish Level of
      Living Surveys (LNU). Young adults' (aged 20-28, n = 803) drinking patterns and
      educational attainment were determined through the LNU 2010 and official
      registers. A decade earlier, parents self-reported their education and drinking
      patterns in the LNU 2000 and Partner-LNU 2000. Results: Logistic regression
      models showed that high parental education predicted young adult frequent
      drinking, while low parental education predicted young adult high quantity
      drinking. Drinking patterns were associated inter-generationally, but parental
      alcohol use did not account for differences in young adult drinking patterns by
      parental education. Young adults' own education similarly predicted their
      drinking patterns but did not account for differences in drinking frequency by
      parental education. Differences in drinking quantity by parental education were
      no longer significant when young adults' own education was included in the final
      model. Conclusions: Findings suggest that parental education constitutes an early
      life structural position that confers differential risk for young adult drinking
      patterns. Young adults whose parents had low education were less likely to drink
      frequently but were more likely to drink heavily per occasion, a drinking pattern
      that may place more disadvantaged young adults at a greater health risk.

PMID- 30238056
TI  - Postdictive confidence (but not predictive confidence) predicts eyewitness memory
      accuracy.
AB  - If testing conditions are uncontaminated, confidence at test reliably predicts
      eyewitness memory accuracy. Unfortunately, information about eyewitness
      postdictive confidence (at the time of the identification test) is frequently
      unavailable or not well documented. In cases where postdictive confidence is
      unavailable, a useful indicator of eyewitness accuracy might be an eyewitness's
      predictive confidence made shortly after the event. How do the accuracy of
      predictive and postdictive confidence judgments compare; and do variables
      reported to affect memory (e.g. exposure duration, face race) affect the
      reliability of the confidence-accuracy relationship for predictive and
      postdictive judgments? In two experiments, we tested the accuracy of memory
      predictions (immediate and delayed judgments of learning [JOLs]) and postdictions
      (confidence) for same- and cross-race faces. Although delayed high JOLs were
      indicative of higher recognition memory accuracy than delayed low JOLs for both
      same- and cross-race faces, the accuracy of even high predictive JOLs was
      objectively low. Postdictive confidence was a far stronger indicator of memory
      accuracy than predictive JOLs; high postdictive confidence was indicative of high
      accuracy; and this was true for both same- and cross-race recognition memory.

PMID- 30238055
TI  - Decision making with visualizations: a cognitive framework across disciplines.
AB  - Visualizations-visual representations of information, depicted in graphics-are
      studied by researchers in numerous ways, ranging from the study of the basic
      principles of creating visualizations, to the cognitive processes underlying
      their use, as well as how visualizations communicate complex information (such as
      in medical risk or spatial patterns). However, findings from different domains
      are rarely shared across domains though there may be domain-general principles
      underlying visualizations and their use. The limited cross-domain communication
      may be due to a lack of a unifying cognitive framework. This review aims to
      address this gap by proposing an integrative model that is grounded in models of
      visualization comprehension and a dual-process account of decision making. We
      review empirical studies of decision making with static two-dimensional
      visualizations motivated by a wide range of research goals and find significant
      direct and indirect support for a dual-process account of decision making with
      visualizations. Consistent with a dual-process model, the first type of
      visualization decision mechanism produces fast, easy, and computationally light
      decisions with visualizations. The second facilitates slower, more contemplative,
      and effortful decisions with visualizations. We illustrate the utility of a dual
      process account of decision making with visualizations using four cross-domain
      findings that may constitute universal visualization principles. Further, we
      offer guidance for future research, including novel areas of exploration and
      practical recommendations for visualization designers based on cognitive theory
      and empirical findings.

PMID- 30238057
TI  - Problematic Mobile Phone Use and Addiction Across Generations: the Roles of
      Psychopathological Symptoms and Smartphone Use.
AB  - Contemporary technological advances have led to a significant increase in using
      mobile technologies. Recent research has pointed to potential problems as a
      consequence of mobile overuse, including addiction, financial problems, dangerous
      use (i.e. whilst driving) and prohibited use (i.e. use in forbidden areas). The
      aim of this study is to extend previous findings regarding the predictive power
      of psychopathological symptoms (depression, anxiety and stress), mobile phone use
      (i.e. calls, SMS, time spent on the phone, as well as the engagement in specific
      smartphone activities) across Generations X and Y on problematic mobile phone use
      in a sample of 273 adults. Findings revealed prohibited use and dependence were
      predicted by calls/day, time on the phone and using social media. Only for
      dependent mobile phone use (rather than prohibited), stress appeared as
      significant. Using social media and anxiety significantly predicted belonging to
      Generation Y, with calls per day predicted belonging to Generation X. This
      finding suggests Generation Y are more likely to use asynchronous social media
      based communication, whereas Generation X engage more in synchronous
      communication. The findings have implications for prevention and awareness
      raising efforts of possibly problematic mobile phone use for educators, parents
      and individuals, particularly including dependence and prohibited use.

PMID- 30238058
TI  - Evaluation of a Web-Based Stress Management Application-a Feasibility Study.
AB  - The aim of the current study was to investigate the feasibility of a Web-based
      program that promotes behavior change for stress-related problems in terms of the
      program's acceptability, practicability, and any possible effects. In addition,
      the aim was also to study how appropriate and realistic the study's process and
      resource management would be for conducting a randomized controlled trial. A
      convenience sample consisting of 14 individuals was recruited from a university
      in Sweden. The participants had access to the program for a duration of 9 weeks.
      Questionnaires were answered before accessing, during use of, and after
      completing the program. Both qualitative and quantitative data were collected and
      analyzed. The program was considered acceptable and practically feasible, though
      small adjustments have to be made. The program was considered time-consuming,
      extensive, and in need of some clarifications. Regarding process and resource
      management, the study participants required minimum support. It was difficult to
      identify the time point when to send out the process measures because the
      participants worked at their own pace. Also, one of the process measurements, the
      motivation to change, remained stable. With some adjustments to the instructions
      to the study participants and minor changes in the program, the intervention and
      study's procedure were considered as feasible and can be carried out in a
      randomized controlled trial.

PMID- 30238059
TI  - Copy number variation analysis increases the diagnostic yield in muscle diseases.
AB  - Objective: Copy number variants (CNVs) were analyzed from next-generation
      sequencing data, with the aim of improving diagnostic yield in skeletal muscle
      disorder cases. Methods: Four publicly available bioinformatic analytic tools
      were used to analyze CNVs from sequencing data from patients with muscle
      diseases. The patients were previously analyzed with a targeted gene panel for
      single nucleotide variants and small insertions and deletions, without achieving
      final diagnosis. Variants detected by multiple CNV analysis tools were verified
      with either array comparative genomic hybridization or PCR. The clinical
      significance of the verified CNVs was interpreted, considering previously
      identified variants, segregation studies, and clinical information of the patient
      cases. Results: Combining analysis of all different mutation types enabled
      integration of results and identified the final cause of the disease in 9
      myopathy cases. Complex effects like compound heterozygosity of different
      mutation types and compound disease arising from variants of different genes were
      unraveled. We identified the first large intragenic deletion of the titin (TTN)
      gene implicated in the pathogenesis of a severe form of myopathy. Our work also
      revealed a "double-trouble" effect in a patient carrying a single heterozygous
      insertion/deletion mutation in the TTN gene and a Becker muscular dystrophy
      causing deletion in the dystrophin gene. Conclusions: Causative CNVs were
      identified proving that analysis of CNVs is essential for increasing the
      diagnostic yield in muscle diseases. Complex severe muscular dystrophy phenotypes
      can be the result of different mutation types but also of the compound effect of
      2 different genetic diseases.

PMID- 30238060
TI  - Randomized Trial of Motivational Interviewing to Prevent Early Childhood Caries
      in Public Housing.
AB  - Introduction: Caries experience among preschool-age children has remained
      relatively unchanged for the past 2 decades, despite recently documented
      decreases in untreated decay. Objectives: In a community-based cluster-randomized
      controlled trial, a motivational interviewing (MI) intervention administered to
      primary caregivers was hypothesized to reduce caries increment over 2 y as
      compared with controls, among children aged 0 to 5 y at baseline living in public
      housing. Methods: Public housing residents, who served as interventionists, were
      trained in MI with a focus on early childhood caries prevention. All 26 eligible
      public housing developments were randomized to either control (quarterly clinical
      examinations, fluoride varnish applications, toothbrush/toothpaste, and
      educational brochures) or intervention (same procedures as control plus MI
      counseling). Quarterly MI sessions were delivered in English or Spanish over 2 y,
      audio recorded, and assessed for treatment fidelity. The primary outcome was the
      increment in dmfs (decayed, missing, and filled tooth surfaces) as assessed by
      clinical examination at baseline, 12 mo, and 24 mo. Secondary outcomes included
      caregiver oral health knowledge and child oral health behaviors (child
      toothbrushing and sugar-sweetened beverage intake). Baseline characteristics were
      compared between groups and adjusted for housing-site clusters. Longitudinal
      outcomes were analyzed with mixed models. Results: A total of 1,065 children (49%
      female, 55% non-White, 61% Hispanic, 89% below poverty level, n = 686 control)
      and their caregivers were enrolled. During 2 y of follow-up, the mean dmfs
      increment increased in both groups; however, there were no statistically
      significant group differences at 24 mo or group * time interactions. The mean
      increase in intervention caregivers' knowledge was significantly greater than
      that of control, F(2, 1,593) = 3.48, P = 0.0310, but there were no significant
      intervention effects on caregiver-reported child sugar-sweetened beverage intake
      or child toothbrushing. Conclusion: MI counseling plus intensive caries
      prevention activities resulted in knowledge increases but did not improve oral
      health behaviors or caries increment (ClinicalTrials.gov NCT01205971). Knowledge
      Transfer Statement: When viewed in light of the findings from the companion Pine
      Ridge study and other recent MI studies, the results of this study suggest that
      when the complex disease of early childhood caries is addressed in high-risk
      populations, MI is not effective, and alternative approaches are warranted.

PMID- 30238061
TI  - Randomized Trial of Motivational Interviewing to Prevent Early Childhood Caries
      in American Indian Children.
AB  - Introduction: In a randomized controlled trial, the effectiveness of motivational
      interviewing (MI) combined with enhanced community services (MI + ECS) was
      compared with ECS alone for reducing dental caries in American Indian children on
      the Pine Ridge Reservation. The intervention was developed and delivered with
      extensive tribal collaboration. Methods: A total 579 mother-newborn dyads were
      enrolled and randomized to the MI + ECS and ECS groups. They were followed for 36
      mo. Four MI sessions were provided, the first shortly after childbirth and then
      6, 12, and 18 mo later. Both groups were exposed to ECS, which included public
      service announcements through billboards and tribal radio, as well as broad
      distribution of brochures on behavioral risk factors for early childhood caries
      (ECC), toothbrushes, and toothpaste. MI impact was measured as decayed, missing,
      and filled tooth surfaces (dmfs). Secondary outcomes included decayed surfaces,
      caries prevalence, and maternal oral health knowledge and behaviors. Modified
      intention-to-treat analyses were conducted. Eighty-eight percent of mothers
      completed at least 3 of 4 MI sessions offered. Results: After 3 y, dmfs was not
      significantly different for the 2 groups (MI + ECS = 10, ECS = 10.38, P = 0.68).
      In both groups, prevalence of caries experience was 7% to 9% after 1 y, 35% to
      36% at 2 y, and 55% to 56% at 3 y. Mean knowledge scores increased by 5.0, 5.3,
      and 5.9 percentage points at years 1, 2, and 3 in the MI + ECS group and by 1.9,
      3.3, and 5.0 percentage points in the ECS group (P = 0.03), respectively. Mean
      maternal oral health behavior scores were not statistically significantly
      different between the treatment arms. Conclusion: In summary, the MI intervention
      appeared to improve maternal knowledge but had no effect on oral health behaviors
      or on the progression of ECC (ClinicalTrials.gov NCT01116726). Knowledge Transfer
      Statement: The findings of this study suggest that motivational interviewing
      focusing on parental behaviors may not be as effective as previously hoped for
      slowing the development of childhood caries in some high-risk groups.
      Furthermore, social factors may be even more salient determinants of oral health
      than what we previously supposed, perhaps interfering with the capacity to
      benefit from behavioral strategies that have been useful elsewhere. The
      improvement of children's oral health in high-risk populations characterized by
      poverty and multiple related life stresses may require more holistic approaches
      that address these formidable barriers.

PMID- 30238063
TI  - Relationship between big five personality factors, problem solving and medical
      errors.
AB  - Background: Human behavior is recognized as the main factor in the occurrence of
      accidents (70-90 percent), with human personality and problem solving ability as
      two related factors in the occurrence of medical errors (annually 42.7 million in
      the world). The objectives of this study were to investigate the relationship
      between personality factors, problem solving ability and medical errors. Material
      and methods: This study was a questionnaire case control study. Information on 49
      members of medical and nursing staff with medical errors (case group) and 46
      without medical errors (control group) were analyzed. To collect the data, two
      Heppner problem solving questionnaires and the NEO-Five Factor Inventory were
      used, which were completed by the study population. Results: The results
      illustrate that individuals without medical errors showed higher scores in
      contentiousness, extraversion and agreeableness and lower scores in neuroticism
      than those with medical errors. Individuals without medical errors also showed
      higher scores in problem solving ability scales than those with medical errors.
      Conclusion: Results of this study, suggest that personality factors and problem
      solving ability are related to medical errors and it may be possible for hospital
      authorities to use this knowledge when selecting capable medical staff.

PMID- 30238062
TI  - In vivo biological fate of poly(vinylalcohol) microbubbles in mice.
AB  - Microbubbles (MBs) are used in clinical practice as vascular ultrasound contrast
      agents, and are gaining popularity as a platform supporting multimodal imaging
      and targeted therapy, facilitating drug delivery under ultrasound exposure. Here,
      we report on the in vivo biological impact of newly discovered MBs with promising
      features as a multimodal theranostic device. The shell of the air-filled MBs is
      made of the poly(vinyl alcohol) (PVA), a well-established, FDA-approved polymer.
      Nevertheless, as size, shape and dispersity can significantly impact the
      biological response of particulate systems, studying their fate after
      administration is crucial. The safety and the biodistribution of PVA MBs were
      analysed in vivo and ex vivo by coupling a near infrared (NIR) fluorophore on
      their shell: MBs accumulated mainly in liver and spleen at 24 hours post
      injection with their clearance from the spleen 7 days post-dosing. A possible way
      of elimination was identified in macrophages ability to engulf MBs both in vitro
      and in vivo. One month post-dosing, transmission electron microscopy (TEM)
      highlighted the lack of relevant defects and the elimination of PVA MBs by
      Kupffer cells. This study is the first successful attempt to fill the lack of
      knowledge necessary to bring PVA MBs one step closer to their possible clinical
      use.

PMID- 30238064
TI  - Antibiotic multidrug resistance in the cystic fibrosis airway microbiome is
      associated with decreased diversity.
AB  - Background: Cystic fibrosis (CF) is associated with significant morbidity and
      early mortality due to recurrent acute and chronic lung infections. The chronic
      use of multiple antibiotics increases the possibility of multidrug resistance
      (MDR). Antibiotic susceptibility determined by culture-based techniques may not
      fully represent the resistance profile. The study objective was to detect
      additional antibiotic resistance using molecular methods and relate the presence
      of MDR to airway microbiome diversity and pulmonary function. Methods: Bacterial
      DNA was extracted from sputum samples and amplified for the V4 region of the 16S
      rRNA gene. An qPCR array was used to detect antibiotic resistance genes. Clinical
      culture results and pulmonary function were also noted for each encounter.
      Results: Six study participants contributed samples from 19 encounters. Those
      samples with MDR (n = 7) had significantly lower diversity measured by inverse
      Simpson's index than those without (n = 12) (2.193 +/- 0.427 vs 6.023 +/- 1.564,
      p = 0.035). Differential abundance showed that samples with MDR had more
      Streptococcus (p = 0.002) and Alcaligenaceae_unclassified (p = 0.002). Pulmonary
      function was also decreased when MDR was present (FEV1, 51 +/- 22.9 vs 77 +/-
      26.7, p = 0.054; FVC, 64.5 +/- 22.7 vs 91.6 +/- 27.7, p = 0.047). Conclusions:
      The presence of MDR within the CF airway microbiome was associated with decreased
      microbial diversity, the presence of Alcaligenes, and decreased pulmonary
      function.

PMID- 30238066
TI  - Packaging to prolong shelf life of preservative-free white bread.
AB  - This research studied various types of packaging to prolong the shelf life of non
      preservative white bread. Three types of blown film packages were used, i.e. a
      single LDPE layer incorporated with an oxygen scavenger, a single LDPE layer
      containing an oxygen absorber sachet, and three layers of LDPE laminated with O
      nylon. The effects of modified packaging atmosphere, i.e. 5, 10, and 21 vol. % of
      oxygen in nitrogen balance, on the shelf life was also included. Characterization
      of the packaging films was carried out using several techniques, such as Oxygen
      Transmission Rate (OTR) and an optical microscopy. Headspace gases, microbial
      count, as well as physical appearance were used to evaluate the shelf life. The
      optical microscopic images showed that incorporating the oxygen scavenger into
      the plastic film produced small pores, contributing to a passive function of the
      films as their OTRs were significantly enhanced. However, the microbial growth on
      bread stored in those packages was suppressed, implying that the intermediate
      generated from scavenging reaction might act as a fungistatic. Even though the
      scavenging capability of the oxygen absorber sachet lasted only for 4 days, the
      fungi and mould development thereafter was still lower compared to the package
      without the sachet. The prolonging white bread shelf life was found to be
      primarily dependent on two factors. The package with a high oxygen barrier such
      three-layer films defeated microorganisms. With a low initial oxygen level of
      around 5% by volume, the bread shelf life could be prolonged up to 5-7 days.

PMID- 30238067
TI  - Aicardi syndrome in a 20-year-old female.
AB  - Purpose: To describe an unusual case of Aicardi Syndrome that both affirms
      hallmark characteristics of the condition and introduces new observations.
      Observations: We report the case of a 20-year-old woman with Aicardi Syndrome who
      presented in respiratory distress with bradycardia and died soon thereafter. She
      had a history of severe mental retardation, seizure disorder, advanced scoliosis
      and numerous contractures in addition to congenital ocular malformations
      resulting in bilateral blindness. The case is notable for her age and longevity,
      as most patients with Aicardi Syndrome expire much younger, as well as the
      presence of intact nuclei under the posterior lens capsule. Conclusions and
      importance: Aicardi Syndrome is a rare X-linked cerebro-retinal disorder typified
      by seizures, agenesis of the corpus callosum, and chorioretinal lacunae.
      Documenting alterations from and additions to this triad of symptoms is critical
      to better understanding both the syndrome itself, as well as the full breadth of
      its clinical impact on the patient.

PMID- 30238065
TI  - Modulation in the microRNA repertoire is responsible for the stage-specific
      effects of Akt suppression on murine neuroendocrine prostate cancer.
AB  - Recent studies indicate a stage-specific, differential role for the oncogene Akt
      on various cancers. In prostate cancer (PCa), suppression of Akt activity in the
      advanced stages promoted transforming growth factor-beta (TGFbeta) pathway
      mediated epithelial-to-mesenchymal transition (EMT) and metastasis to the lungs.
      In the current study, we performed Affymetrix analysis to compare the expression
      profile of microRNAs in the mouse prostate tissues collected at the prostatic
      inter-epithelial neoplasia (PIN) stage from Transgenic adenocarcinoma of the
      mouse (TRAMP)/Akt1+/+ versus TRAMP/Akt1-/- mice, and at the advanced stage from
      TRAMP/Akt1+/+ mice treated with triciribine (Akt inhibitor) versus DMSO-treated
      control. Our analysis demonstrates that in the early stage, Akt1 in the TRAMP
      prostate tumors express a set of miRNAs responsible for regulating cancer cell
      survival, proliferation, and tumor growth, whereas, in the advanced stages, a
      different set of miRNAs that promote EMT and cancer metastasis is expressed. Our
      study has identified novel Akt-regulated signature microRNAs in the early and
      advanced PCa and demonstrates their differential effects on PCa growth and
      metastasis.

PMID- 30238068
TI  - Endothelial barrier dysfunction induced by nanoparticle exposure through actin
      remodeling via caveolae/raft-regulated calcium signalling.
AB  - The rapid development of modern nanotechnology has resulted in nanomaterial being
      use in nearly all applications of life, raising the potential risk of
      nanomaterial exposure alongside the need to design safe and effective materials.
      Previous work has demonstrated a specific effect of gold nanoparticles (GNPs) of
      approximately 20 nm on endothelial barrier function in vitro. To expand our
      understanding of this size-specific effect, titanium dioxide, silicon dioxide,
      and polystyrene nanoparticles (NPs) in this similar size range were studied. All
      tested nanoparticles were found to have minimal effects on cell viability, but
      exhibited a significant detrimental effect on endothelial barrier function.
      Nanoparticles in the size range of 20 to 30 nm were internalized by endothelial
      cells through caveolae/raft-mediated endocytosis, causing intracellular calcium
      elevation by approximately 30% at 2 hours after administration, and triggering
      myosin light chain kinase (MLCK)-regulated actomyosin contraction. These effects
      culminated in an increase in endothelial monolayer permeability across all
      particle types within the 20-30 nm range. This nanoparticle exposure-induced
      endothelial barrier dysfunction may provide valuable information for designing
      safer nanomaterials or potential applications of this nanoparticle exposure
      induced permeability effect in biomedicine.

PMID- 30238069
TI  - Quantitative Evaluation of Choroidal Neovascularization under Pro Re Nata Anti
      Vascular Endothelial Growth Factor Therapy with OCT Angiography.
AB  - Purpose: To use optical coherence tomography angiography (OCTA) derived
      quantitative metrics to assess the response of choroidal neovascularization to
      pro-re-nata (PRN) anti-endothelial growth factor (anti-VEGF) treatment in
      neovascular age-related macular degeneration (AMD). Design: Prospective
      longitudinal cohort study. Participants: Fourteen eyes from 14 study participants
      with treatment-naive neovascular AMD were enrolled. Methods: Subjects were
      evaluated monthly and treated with intravitreal anti-VEGF agents under a PRN
      protocol for one year. At each visit, two 3*3 mm2 OCTA scans were obtained.
      Custom image processing was applied to segment the outer retinal slab, suppress
      projection artifact, and automatically detect CNV. CNV membrane area (mm2) and
      CNV vessel area (mm2) was calculated. Main Outcomes: Individual and mean CNV
      membrane area and CNV vessel area at each visit; within-visit repeatability
      determined by coefficient of variation. Results: Eight eyes had entire CNV within
      3*3 mm2 scanning area and had adequate image quality for CNV quantification. One
      case (case #2) was excluded from analysis due to the presence of a large
      subretinal hemorrhage overlying the CNV membrane. In the remaining cases, CNV
      vessel area was reduced by 39%, 50%, 43%, and 41% at months 1, 3, 6, and 12
      respectively. CNV membrane area was reduced by 39%, 51%, 54%, and 45% at months
      1, 3, 6, and 12. At month 6, mean change from baseline was not statistically
      significant for CNV vessel area, while it was statistically significant for CNV
      membrane area. Neither metric was significantly different compared to baseline at
      month 12. Individual analyses revealed each CNV had a unique response under PRN
      treatment. Within-visit repeatability was was 7.96% (coefficient of variation)
      for CNV vessel area and 7.37% for CNV membrane area. Conclusions: In this small
      exploratory study of CNV response to PRN anti-VEGF treatment, both CNV vessel
      area and membrane area were reduced compared to baseline after three months.
      After one year of follow-up, these reductions were no longer statistically
      significant. When anti-VEGF treatment was held, increasing CNV vessel area over
      time often resulted in exudation, but it was not possible to exactly when
      exudation occurs.

PMID- 30238070
TI  - Computerized Approach to Creating a Systematic Ontology of Hematology/Oncology
      Regimens.
AB  - Purpose: The systemic treatment of cancer is primarily through the administration
      of complex chemotherapy protocols. To date, this knowledge has not been
      systematized, because of the lack of a consistent nomenclature and the variation
      in which regimens are documented. For example, recording of treatment events in
      electronic health record notes is often through shorthand and acronyms, limiting
      secondary use. A standardized hierarchic ontology of cancer treatments, mapped to
      standard nomenclatures, would be valuable to a variety of end users. Methods: We
      leveraged the knowledge contained in a large wiki of hematology/oncology drugs
      and treatment regimens, HemOnc.org. Through algorithmic parsing, we created a
      hierarchic ontology of treatment concepts in the World Wide Web Consortium Web
      Ontology Language. We also mapped drug names to RxNorm codes and created optional
      filters to restrict the ontology by disease and/or drug class. Results: As of
      December 2017, the main ontology includes 30,526 axioms (eg, doxorubicin is an
      anthracycline), 1,196 classes (eg, regimens used in the neoadjuvant treatment of
      human epidermal growth factor receptor 2-positive breast cancer, nitrogen
      mustards), and 1,728 individual entities. More than 13,000 of the axioms are
      annotations including RxNorm codes, drug synonyms, literature references, and
      direct links to published articles. Conclusion: This approach represents, to our
      knowledge, the largest effort to date to systematically categorize and relate
      hematology/oncology drugs and regimens. The ontology can be used to reason
      individual components from regimens mentioned in electronic health records (eg, R
      CHOP maps to rituximab, cyclophosphamide, doxorubicin, vincristine, and
      prednisone) and also to probabilistically reconstruct regimens from individual
      drug components. These capabilities may be particularly valuable in the
      implementation of rapid-learning health systems on the basis of real-world
      evidence. The derived Web Ontology Language ontology is freely available for
      noncommercial use through the Creative Commons 4.0 Attribution-NonCommercial
      ShareAlike license.

PMID- 30238072
TI  - Management of lateral pelvic lymph node in the East: Time to learn from the
      Western viewpoints.

PMID- 30238071
TI  - SMART Cancer Navigator: A Framework for Implementing ASCO Workshop
      Recommendations to Enable Precision Cancer Medicine.
AB  - Purpose: Data standards and interoperability are critical for improving care for
      patients with cancer. Recent efforts by ASCO include the Data Standards and
      Interoperability Summit in 2016, which led to the Omics and Precision Oncology
      and Advancing Interoperability workshops. To facilitate improved patient care,
      several recommendations for data sharing and standardization were made to the
      community. Methods: To address these recommendations, we developed SMART Cancer
      Navigator, a Web application that uses application programming interfaces to
      gather clinical and genomic data from 11 public knowledge bases ranging from
      basic to clinical content coverage; three (CIViC, ClinVar, and OncoKB) explicitly
      linked genomic variants to clinical factors such as prognosis and treatment
      selection. We illustrated the utility of this application by selecting one of the
      monthly case studies presented by the ASCO University Molecular Oncology Tumor
      Board: Ovarian Cancer (BRCA Mutation). We also performed analyses on information
      from the three clinico-genomic knowledge bases to corroborate previous work and
      illustrate the state of data sharing among publicly available resources. Results:
      SMART Cancer Navigator aggregates and contextualizes data from 11 different
      knowledge bases and stores user queries in a lightweight Web application that can
      link into Fast Healthcare Interoperability Resources-enabled electronic health
      records. Potentially relevant clinical trials and/or approved treatments were
      identified for three mutations found in a hypothetical patient with advanced
      ovarian cancer. A comparison of the three clinico-genomic knowledge bases
      indicated substantial differences in coverage at the gene and variant levels.
      Conclusion: SMART Cancer Navigator has immediate relevance to practicing
      oncologists and others. Additional knowledge bases can be added without undue
      effort. As a first step toward utility, we generalized and disseminated the
      resulting implementation (https://smart-cancer-navigator.github.io) and data
      sets.

PMID- 30238073
TI  - Cancer evolution and heterogeneity.
AB  - Undoubtedly, intratumor heterogeneity (ITH) is one of the causes of the
      intractability of cancers. Recently, technological innovation in genomics has
      promoted studies on ITH in solid tumors and on the pattern and level of
      diversity, which varies among malignancies. We profiled the genome in multiple
      regions of nine colorectal cancer (CRC) cases. The most impressive finding was
      that in the late phase, a parental clone branched into numerous subclones. We
      found that minor mutations were dominant in advanced CRC named neutral evolution;
      that is, driver gene aberrations were observed with high proportion in the early
      acquired phase, but low in the late-acquired phase. Then, we validated that
      neutral evolution could cause ITH in advanced CRC by super-computational
      analysis. According to the clinical findings, we explored a branching
      evolutionary process model in cancer evolution, which assumes that each tumor
      cell has cellular automaton. According to the model, we verified factors to
      foster ITH with neutral evolution in advanced CRC. In this review, we introduce
      recent advances in the field of ITH including the general component of ITH,
      clonal selective factors that consolidate the evolutionary process, and a
      representative clinical application of ITH.

PMID- 30238075
TI  - Lateral pelvic lymph node dissection and radiation treatment for rectal cancer:
      Mutually exclusive or mutually beneficial?
AB  - Lateral pelvic lymph nodes (LPLN) in mid-/low rectal cancer pose a theoretical
      and practical challenge for the clinician and the patient, with geographical
      differences in management based on historical competing priorities. Although
      there has been a tendency to think of neoadjuvant radiation versus intraoperative
      LPLN dissection as a binary choice, they should be more constructively seen as
      complementary options in the personalized management of patients with rectal
      cancer. Herein we propose one potential algorithm for using these treatment
      options in this way based on local preoperative staging and the current evidence
      available. We also outline future research priorities in this area with the aim
      of answering several residual questions that remain.

PMID- 30238074
TI  - Surgery with curative intent for stage IV gastric cancer: Is it a reality of
      illusion?
AB  - Gastric cancer with metastases outside of the regional lymph nodes is deemed
      oncologically unresectable. Nevertheless, some metastatic lesions are technically
      resectable by applying established surgical techniques such as para-aortic
      lymphadenectomy and hepatectomy. At the time of compilation of the Japanese
      gastric cancer treatment guidelines version 4, systematic reviews were conducted
      to see whether it is feasible to make any recommendation to dissect both the
      primary and metastatic lesions with intent to cure, possibly as part of
      multimodality treatment. Long-term survivors were found among carefully selected
      groups of patients both in prospective and retrospective studies. In addition,
      there is a growing list of publications reporting encouraging outcomes of
      gastrectomy conducted after exceptionally good response to chemotherapy, usually
      among patients who underwent R0 resection. This type of surgery is often referred
      to as conversion surgery. It is sometimes difficult to define a clear borderline
      between curative surgery scheduled after neoadjuvant chemotherapy and the
      conversion surgery. This review summarizes what we knew after the literature
      reviews conducted at the time of compiling the Japanese guidelines and in
      addition reflects some new findings obtained thereafter through clinical trials
      and retrospective studies. Metastases were divided into three categories based on
      the major metastatic pathways: lymphatic, hematogenous, and peritoneal. In each
      of these categories, there were findings that could provide hope for patients
      with metastatic disease. These findings implied that the surgical technique that
      we already use could become more useful upon further developments in
      antineoplastic agents and drug delivery.

PMID- 30238076
TI  - Mechanisms of sepsis-induced immunosuppression and immunological modification
      therapies for sepsis.
AB  - Surgical injury can be a life-threatening complication, not only due to the
      injury itself, but also due to immune responses to the injury and subsequent
      development of infections, which readily result in sepsis. Sepsis remains the
      leading cause of death in most intensive care units. Unfavorable outcomes of
      several high-profile trials in the treatment of sepsis have led researchers to
      state that sepsis studies need a new direction. The immune response that occurs
      during sepsis is characterized by a cytokine-mediated hyper-inflammatory phase,
      which most patients survive, and a subsequent immunosuppressive phase. Therefore,
      therapies that improve host immunity might increase the survival of patients with
      sepsis. Many mechanisms are responsible for sepsis-induced immunosuppression,
      including apoptosis of immune cells, increased regulatory T cells and expression
      of programmed cell death 1 on CD4+ T cells, and cellular exhaustion.
      Immunomodulatory molecules that were recently identified include interleukin-7,
      interleukin-15, and anti-programmed cell death 1. Recent studies suggest that
      immunoadjuvant therapy is the next major advance in sepsis treatment.

PMID- 30238077
TI  - Surgical management of carcinoma in situ at ductal resection margins in patients
      with extrahepatic cholangiocarcinoma.
AB  - Recent advances in dimensional imaging, surgical technique, and perioperative
      patient care have resulted in increased rates of complete resection with
      histopathologically negative margins and improved surgical outcomes in patients
      with extrahepatic cholangiocarcinoma. However, achieving cancer-free resection
      margins at ductal stumps in surgery for this disease remains challenging because
      of longitudinal extension, which is one of the hallmarks of extrahepatic
      cholangiocarcinoma. When the ductal resection margins are shown to be positive on
      examination of frozen sections, discrimination between carcinoma in situ and
      invasive carcinoma is clinically important because residual carcinoma in situ may
      lead to late local recurrence whereas residual invasive carcinoma is associated
      with early local recurrence. Residual invasive carcinoma at the ductal margins
      should be avoided whenever technically feasible. Residual "carcinoma in situ" at
      the ductal margins appears to be allowed in resection for the advanced disease
      because it has less effect on survival than other adverse prognostic factors (pN1
      and/ or pM1). However, in surgery for early-stage (pTis-2N0M0) extrahepatic
      cholangiocarcinoma, residual carcinoma in situ at the ductal margins may have an
      adverse effect on long-term survival, so should be avoided whenever possible. In
      this review, we focus on the histopathological term "carcinoma in situ," the
      biological behavior of residual carcinoma in situ at ductal resection margins,
      intraoperative histological examination of the ductal resection margins, outcome
      of additional resection for positive ductal margins, and adjuvant therapy for
      patients with positive margins.

PMID- 30238079
TI  - Laparoscopic left hemihepatectomy is suitable as a first step in pure
      laparoscopic major hepatectomy.
AB  - Aim: As a procedure, major laparoscopic liver resection (LLR) remains in the
      exploration phase. Previous studies have assessed major LLR en bloc, including
      hepatectomies of varying complexities; however, the number of segments alone does
      not convey the complexity of a resection. This study aimed to assess operative
      outcomes of LLR procedures with more than one sectionectomy, and to identify the
      best procedure as a first step when learning to carry out major LLR in order to
      make LLR a safer, more widely used procedure. Methods: We carried out a
      retrospective review of the operative outcomes of 120 consecutive patients who
      underwent pure LLR with more than one sectionectomy. Operative outcomes were
      compared according to the complexity classification recently published, and the
      learning curve for each LLR procedure was assessed and compared. Results:
      Operative outcomes, including operative time, blood loss, and the comprehensive
      complication index, were significantly stratified according to complexity. There
      were significant differences in operative outcomes among the medium complexity
      procedures. The operative time for left hemihepatectomy was the shortest, and the
      amount of blood loss was the lowest among the medium complexity LLR. Operative
      times for left hemihepatectomy shortened significantly with time and experience
      (r = -0.639), and the slope of the learning curve was steeper than for right
      hemihepatectomy and right posterior sectionectomy. Conclusion: Left
      hemihepatectomy is suitable as a first step in pure laparoscopic major
      hepatectomy and, given its safety and rapid learning curve for surgeons, it could
      become the gold standard procedure.

PMID- 30238078
TI  - Preoperative globulin-to-albumin ratio predicts outcome after curative resection
      in patients with gastric cancer.
AB  - Aim: The globulin-to-albumin ratio (GAR) is useful for prognostication of
      patients with various cancers. However, the significance of GAR in gastric cancer
      (GC) remains unclear. Our purpose was to investigate the relationship between the
      GAR and outcome after curative resection in GC patients. Methods: Three-hundred
      and seventy-six patients who had undergone curative resection for GC were
      retrospectively reviewed. Univariate and multivariate analyses using the Cox
      proportional hazard model were performed to detect clinical characteristics that
      correlated with overall survival (OS), and their cut-off values were identified
      using receiver operating characteristic (ROC) curve analyses. Kaplan-Meier
      analysis and log-rank test were used for comparison of OS and relapse-free
      survival (RFS). Results: Multivariate analysis using 17 clinical characteristics
      selected by univariate analyses revealed that GAR (>0.80/<=0.80) was
      significantly associated with OS (hazard ratio [HR], 2.305; 95% CI, 1.122-4.735;
      P = 0.023), as well as lymph node metastasis (presence/absence) (HR, 2.417; 95%
      CI, 1.077-5.426; P = 0.032), neutrophil-to-lymphocyte ratio (>2.7/<=2.7) (HR,
      2.368; 95% CI, 1.138-4.930; P = 0.002), and serosal invasion (presence/absence)
      (HR, 3.443; 95% CI, 1.048-11.31; P = 0.042). Kaplan-Meier analysis and log-rank
      test demonstrated that the OS and RFS of patients with a high GAR (>0.80) were
      significantly poorer than those with low GAR (<=0.80). Conclusions: The GAR is a
      useful predictor of postoperative outcome among GC patients undergoing curative
      resection.

PMID- 30238081
TI  - Is surgical treatment necessary for uncomplicated acute appendicitis?

PMID- 30238080
TI  - Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer
      cell activity in colorectal cancer with resectable liver metastasis.
AB  - Aim: We investigated the chemotherapy effect of resectable colorectal cancer with
      liver metastasis (CRLM) on the function of intrahepatic immune cells. Methods: We
      classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after
      hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy
      group (group B), and collected peripheral blood mononuclear cells (PBMC) and
      liver mononuclear cells (LMNC) to ascertain phenotypic and functional
      differences. Results: There were no significant differences in lymphocyte
      fractions of either PBMC or LMNC between groups, except for the significantly
      lower percentage of natural killer (NK) cells in LMNC in group B than in group A.
      Significantly higher percentage of natural-killer group 2, member D (NKG2D)-
      positive NK cells in PBMC and percentage of tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL)-, NKp30-, and signal regulatory protein beta
      (SIRPbeta)-positive NK cells in LMNC were found in group B. Furthermore,
      significantly higher expressions of NKG2D and SIRPbeta in peripheral blood NK
      cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC
      were incubated with interleukin (IL)-2 in vitro, no difference was observed in
      the expression of these molecules in NK cells between groups. Consistently, there
      was no difference in the cytotoxic activity of those LMNC against a colon
      adenocarcinoma cell line between groups. Conclusion: Colorectal cancer with liver
      metastasis patients treated with neoadjuvant chemotherapy showed enhanced
      expression of activation markers on peripheral blood and liver NK cells in
      comparison with patients who did not receive therapy; however, the difference in
      those function remains unclear. These results suggest that neoadjuvant
      chemotherapy does not have a negative impact on intrahepatic immune cells in
      resectable CRLM patients.

PMID- 30238082
TI  - Consequences of screening in abdominal aortic aneurysm: development and
      dimensionality of a questionnaire.
AB  - Background: In interview studies, men under surveillance for screening-detected
      abdominal aortic aneurysms have reported ambivalence towards this diagnosis: the
      knowledge was welcomed together with worries, feelings of anxiety and existential
      thoughts about life's fragility and mortality due to the diagnosis. Previous
      surveys about health-related quality of life aspects among men under surveillance
      for screening-detected aneurysm have all used generic patient-reported outcomes.
      Therefore, the aim of this study was to extend the core-questionnaire
      Consequences of Screening for use in abdominal aortic aneurysm screening by
      testing for comprehension, content coverage, dimensionality, and reliability.
      Methods: In interviews, the suitability, content coverage, and relevance of the
      core-questionnaire Consequences of Screening were tested on men under
      surveillance for a screeningdetected abdominal aortic aneurysm. The results were
      thematically analysed to identify the key consequences of abnormal screening
      results. Item Response Theory and Classical Test Theory were used to analyse
      data. Dimensionality, differential item functioning, local response dependency
      and reliability were established by item analysis, examining the fit between item
      responses and Rasch models. Results: The core-questionnaire Consequences of
      Screening was found to be relevant for men offered regular follow-up of an
      asymptomatic screening-detected abdominal aortic aneurysm.Fourteen themes
      especially relevant for men diagnosed with a screening-detected abdominal aortic
      aneurysm were extracted from the interviews: 'Uncertainty about the result of the
      ultra sound examination', 'Change in body perception', 'Guilt', 'Fear and
      powerlessness', 'Negative experiences from the examination', 'Emotional
      reactions', 'Change in lifestyle', 'Better not knowing', 'Fear of rupture',
      'Sexuality', 'Information', 'Stigmatised', 'Self-blame for smoking', 'Still
      regretful smoking'. Altogether, 55 new items were generated: 3 were single items
      and 13 were only relevant for former or current smokers. 51 of the 52 items
      belonging to a theme were confirmed to fit Rasch models measuring fourteen
      different constructs. No differential item functioning and only minor local
      dependency was revealed between some of the 51 items. Conclusions: The
      reliability and the dimensionality of a condition-specific measure with high
      content validity for men under surveillance for a screening-detected abdominal
      aortic aneurysm have been demonstrated. This new questionnaire called COS-AAA
      covers in two parts the psychosocial experience in abdominal aortic aneurysm
      screening.

PMID- 30238083
TI  - PRO-based follow-up as a means of self-management support - an interpretive
      description of the patient perspective.
AB  - Background: There is an increasing focus on the use of patient-reported outcome
      (PRO) measures to improve the quality and effectiveness of health care. PRO-based
      follow-up is a new model of service delivery, where the patient's PRO measures
      are used as the very basis for outpatient follow-up. Objectives: This study aimed
      to explore how patients with epilepsy experience the use of PRO-based follow-up
      in three outpatient clinics in the Central Denmark Region. We also sought to
      explain how these experiences relate to self-management. Methods: Interpretive
      description was the methodological approach. We conducted in-depth individual
      interviews with 29 patients referred to PRO-based follow-up, each of whom had
      completed at least two PRO questionnaires. Participants were sampled based on
      purposive and theoretical sampling. Results: PRO-based follow-up may support
      patients' self-management by a) increasing awareness of psychosocial problems, b)
      improving communication, c) increasing understanding of symptoms, d) facilitating
      change in health behavior and e) strengthening autonomy. Inhibitors for PRO
      measures as a means of self-management support were identified as a) feelings of
      rejection and disconnection, b) incomprehension of purpose of PRO-based follow
      up, c) PRO measures being too standardized and negative and d) lack of confidence
      in own ability to assess PRO questionnaires. Conclusion: The findings demonstrate
      broad variation in the influences of PRO measures on patient's self-management in
      life with epilepsy. Sense of ownership may explain this variation. We suggest
      supplementary clinical initiatives in order to enhance the benefits from PRO
      based follow-up, particularly on how patients are allocated to this health care
      service.

PMID- 30238084
TI  - Literature review to characterize the empirical basis for response scale
      selection in pediatric populations.
AB  - Background: Despite the importance of response option selection for patient
      reported outcome measures, there seems to be little empirical evidence for the
      selected scale type. This article provides an overview of the published research
      on response scale types and empirical support within pediatric populations.
      Methods: A comprehensive review of the scientific literature was conducted to
      identify response scale option types appropriate for use in pediatric populations
      and to review and summarize the available empirical evidence for each scale type.
      Results: Eleven review/consensus guideline/expert opinion articles and 20
      empirical articles that provided guidance or evidence regarding pediatric
      response scale selection were identified. There was general consensus that 5
      point verbal rating scales, including Likert scales, were appropriate for
      children aged 7 or 8 and older, while graphical or faces scales are often used in
      pediatric studies with children of younger ages. Conclusion: In general, the
      verbal rating scale, numeric rating scale, visual analogue scale, and graphical
      scales have each demonstrated to be reliable and valid response option formats in
      specific contexts among pediatric populations; however, their appropriateness is
      dependent upon sample age. When selecting response scales, it is important to
      consider target population and context of use during the development of patient
      reported outcome measures, especially with respect to tense, recall period,
      attribution, number of options, etc. In addition to age, cognitive development is
      an important aspect to consider for optimizing pediatric self-reported measures.
      More research is needed to determine clinically relevant changes and differences
      within pediatric research, which includes different response scale options.

PMID- 30238085
TI  - Response scale selection in adult pain measures: results from a literature
      review.
AB  - Background: The purpose of this literature review was to examine the existing
      patient-reported outcome measurement literature to understand the empirical
      evidence supporting response scale selection in pain measurement for the adult
      population. Methods: The search strategy involved a comprehensive, structured,
      literature review with multiple search objectives and search terms. Results: The
      searched yielded 6918 abstracts which were reviewed against study criteria for
      eligibility across the adult pain objective. The review included 42 review
      articles, consensus guidelines, expert opinion pieces, and primary research
      articles providing insights into optimal response scale selection for pain
      assessment in the adult population. Based on the extensive and varied literature
      on pain assessments, the adult pain studies typically use simple response scales
      with single-item measures of pain-a numeric rating scale, visual analog scale, or
      verbal rating scale. Across 42 review articles, consensus guidelines, expert
      opinion pieces, and primary research articles, the NRS response scale was most
      often recommended in these guidance documents. When reviewing the empirical basis
      for these recommendations, we found that the NRS had slightly superior
      measurement properties (e.g., reliability, validity, responsiveness) across a
      wide variety of contexts of use as compared to other response scales.
      Conclusions: Both empirical studies and review articles provide evidence that the
      11-point NRS is likely the optimal response scale to evaluate pain among adult
      patients without cognitive impairment.

PMID- 30238087
TI  - Respiratory level tracking with visual biofeedback for consistent breath-hold
      level with potential application in image-guided interventions.
AB  - Background: To present and evaluate a new respiratory level biofeedback system
      that aids the patient to return to a consistent breath-hold level with potential
      application in image-guided interventions. Methods: The study was approved by the
      local ethics committee and written informed consent was waived. Respiratory
      motion was recorded in eight healthy volunteers in the supine and prone
      positions, using a depth camera that measures the mean distance to thorax,
      abdomen and back. Volunteers were provided with real-time visual biofeedback on a
      screen, as a ball moving up and down with respiratory motion. For validation
      purposes, a conversion factor from mean distance (in mm) to relative lung volume
      (in mL) was determined using spirometry. Subsequently, without spirometry,
      volunteers were given breathing instructions and were asked to return to their
      initial breath-hold level at expiration ten times, in both positions, with and
      without visual biofeedback. For both positions, the median and interquartile
      range (IQR) of the absolute error in lung volume from initial breath-hold were
      determined with and without biofeedback and compared using Wilcoxon signed rank
      tests. Results: Without visual biofeedback, the median difference from initial
      breath-hold was 124.6 mL (IQR 55.7-259.7 mL) for the supine position and 156.3 mL
      (IQR 90.9-334.7 mL) for the prone position. With the biofeedback, the difference
      was significantly decreased to 32.7 mL (IQR 12.8-59.6 mL) (p < 0.001) and 22.3 mL
      (IQR 7.7-47.0 mL) (p < 0.001), respectively. Conclusions: The use of a depth
      camera to provide visual biofeedback increased the reproducibility of breath-hold
      expiration level in healthy volunteers, with a potential to eliminate targeting
      errors caused by respiratory movement during lung image-guided procedures.

PMID- 30238088
TI  - MUEMA: Microinteraction-based Ecological Momentary Assessment (EMA) Using a
      Smartwatch.
AB  - Ecological Momentary Assessment (EMA) is a method of in situ data collection for
      assessment of behaviors, states, and contexts. Questions are prompted during
      everyday life using an individual's mobile device, thereby reducing recall bias
      and increasing validity over other self-report methods such as retrospective
      recall. We describe a microinteraction-based EMA method ("micro" EMA, or MUEMA)
      using smartwatches, where all EMA questions can be answered with a quick glance
      and a tap - nearly as quickly as checking the time on a watch. A between
      subjects, 4-week pilot study was conducted where MUEMA on a smartwatch (n=19) was
      compared with EMA on a phone (n=14). Despite an ~8 times increase in the number
      of interruptions, MUEMA had a significantly higher compliance rate, completion
      rate, and first prompt response rate, and MUEMA was perceived as less
      distracting. The temporal density of data collection possible with MUEMA could
      prove useful in ubiquitous computing studies.

PMID- 30238086
TI  - Literature review to assemble the evidence for response scales used in patient
      reported outcome measures.
AB  - Background: In the development of patient-reported outcome (PRO) instruments,
      little documentation is provided on the justification of response scale
      selection. The selection of response scales is often based on the developers'
      preferences or therapeutic area conventions. The purpose of this literature
      review was to assemble evidence on the selection of response scale types, in PRO
      instruments. The literature search was conducted in EMBASE, MEDLINE, and PsycINFO
      databases. Secondary search was conducted on supplementary sources including
      reference lists of key articles, websites for major PRO-related working groups
      and consortia, and conference abstracts. Evidence on the selection of verbal
      rating scale (VRS), numeric rating scale (NRS), and visual analogue scale (VAS)
      was collated based on pre-determined categories pertinent to the development of
      PRO instruments: reliability, validity, and responsiveness of PRO instruments,
      select therapeutic areas, and optimal number of response scale options. Results:
      A total of 6713 abstracts were reviewed; 186 full-text references included. There
      was a lack of consensus in the literature on the justification for response scale
      type based on the reliability, validity, and responsiveness of a PRO instrument.
      The type of response scale varied within the following therapeutic areas: asthma,
      cognition, depression, fatigue in rheumatoid arthritis, and oncology. The optimal
      number of response options depends on the construct, but quantitative evidence
      suggests that a 5-point or 6-point VRS was more informative and discriminative
      than fewer response options. Conclusions: The VRS, NRS, and VAS are acceptable
      response scale types in the development of PRO instruments. The empirical
      evidence on selection of response scales was inconsistent and, therefore, more
      empirical evidence needs to be generated. In the development of PRO instruments,
      it is important to consider the measurement properties and therapeutic area and
      provide justification for the selection of response scale type.

PMID- 30238089
TI  - How an electric field can modulate the metal ion selectivity of protein binding
      sites: insights from DFT/PCM calculations.
AB  - Selecting the "right" metal cation from the surrounding
      intracellular/extracellular fluids is of crucial importance for proper
      functioning of metalloproteins. Over the course of a few billion years of cell
      evolution various strategies have been developed by the host protein or cell
      machinery to secure the most favorable conditions for cognate cation binding. The
      effect of internal/external electric fields, potentially capable of influencing
      the process of metal selectivity in proteins, however, remains an enigmatic and
      unexplored area of research. Several outstanding questions remain unanswered: (1)
      Can, and if so, to what extent, an electric field affect the competition between
      different metal species for protein ligands? (2) What type of binding sites (with
      specific architecture, polarizability, and solvent exposure) are more susceptible
      to electric stimuli? (3) How do the basic parameters of the electric field - its
      strength and directionality - modulate the selectivity of the metal binding site?
      (4) What is the upper limit of the electric field magnitude that preserves the
      integrity of the metal binding site? Here, by employing density functional theory
      calculations combined with continuum dielectric method computations, we endeavor
      to shed light on these questions by studying the thermodynamic outcome of the
      competition between Mg2+ and Ca2+ in a model EF-hand motif metal binding site
      under the influence of a dipole electric field with variable magnitude and
      directionality. The calculations reveal that the electric field (either internal
      or external) is a potent force that can modulate the metal selectivity of the
      binding site and thus can be added to the list of factors governing the metal
      competition in metalloproteins. An oriented external electric field with a
      particular directionality could be used as a switch to enhance or attenuate the
      preference of the binding site toward given metal species.

PMID- 30238090
TI  - NiFe2O4 nanoparticles coated on 3D graphene capsule as electrode for advanced
      energy storage applications.
AB  - Current energy crises are inspiring researchers to focus intensively on
      development of feasible ways to produce high performing composite electrode
      materials for increasing energy demands. The present work addresses this
      objective by developing a novel structure of NiFe2O4 (NFO) nanoparticles coated
      on graphene capsules (GCs) by a simple hydrothermal technique. This NFO-GCs
      electrode material was subjected to different types of electrochemical
      performance evaluations to investigate its feasibility as a supercapacitor
      electrode. The as-prepared NFO-GCs nanocomposite electrode exhibits high specific
      capacitance of 1028 F g-1 at a current density of 2 A g-1 and 94% capacitance
      retention at the end of 10 000 charge-discharge cycles, whereas pristine NFO
      electrode shows 720 F g-1 specific capacitance with 88% capacitance retention.
      The high specific capacitance, good rate capability, and excellent cycling
      stability of NFO-GCs composite can be attributed to effective synergism between
      the GCs and NFO. The superior electrochemical performance of NFO-GCs
      nanocomposite demonstrates possible application of this material as a working
      electrode for fully functional supercapacitor devices.

PMID- 30238091
TI  - Human stomach-on-a-chip with luminal flow and peristaltic-like motility.
AB  - Current in vitro approaches and animal models have critical limitations for
      modeling human gastrointestinal diseases because they may not properly represent
      multicellular human primary tissues. Therefore, there is a need for model
      platforms that recapitulate human in vivo development, physiology, and disease
      processes to validate new therapeutics. One of the major steps toward this goal
      was the generation of three-dimensional (3D) human gastric organoids (hGOs) via
      the directed differentiation of human pluripotent stem cells (hPSCs). The normal
      functions and diseases of the stomach occur in the luminal epithelium, however
      accessing the epithelium on the inside of organoids is challenging. We sought to
      develop a bioengineered platform to introduce luminal flow through hGOs to better
      model in vivo gastric functions. Here, we report an innovative microfluidic
      imaging platform housing hGOs with peristaltic luminal flow in vitro. This human
      stomach-on-a-chip allows robust, long-term, 3D growth of hGOs with the capacity
      for luminal delivery via a peristaltic pump. Organoids were cannulated and medium
      containing fluorescent dextran was delivered through the lumen using a
      peristaltic pump. This system also allowed us to rhythmically introduce stretch
      and contraction to the organoid, reminiscent of gastric motility. Our platform
      has the potential for long-term delivery of nutrients or pharmacological agents
      into the gastric lumen in vitro for the study of human gastric physiology,
      disease modeling, and drug screening, among other possibilities.

PMID- 30238092
TI  - Structuring polarity-inverted TBA to G-quadruplex for selective recognition of
      planarity of natural isoquinoline alkaloids.
AB  - Efficient structuring of DNA by small molecules is very crucial in developing DNA
      based novel switches with an ideal performance. In this work, we found that
      inverting only the polarity of the 3' terminal guanine of the thrombin-binding
      aptamer (3iTBA) totally eradicates the original TBA G-quadruplex (G4) structure
      in K+. The unstructured 3iTBA can be further refolded upon specifically
      interacting with small molecules of natural isoquinoline alkaloids (IAs) due to
      their fruitful binding patterns with variant nucleic acid structures. We
      identified that 3iTBA can serve as a topology selector for planar IAs. Nitidine
      (NIT), owing to the planar aromatic ring and coplanar substituents, is the most
      efficient to restructure the 3iTBA random coil toward the anti-parallel G4
      conformation. However, common metal ions can't realize this structuring. The
      topology selector competency of 3iTBA toward IAs' planarity can be visualized
      using gold nanoparticles (AuNPs) as the chromogenic readout. Our work expands the
      G4 repertoire by exploring the polarity inversion regulation and provides a new
      approach to switch nucleic acid structures toward a small molecule structure
      sensitive sensor.

PMID- 30238093
TI  - X-ray emission spectroscopy: an effective route to extract site occupation of
      cations.
AB  - Cation site occupation is an important determinant of materials properties,
      especially in a complex system with multiple cations such as in ternary spinels.
      Many methods for extracting the cation site information have been explored in the
      past, including analysis of spectra obtained through K-edge X-ray absorption
      spectroscopy (XAS). In this work, we measure the effectiveness of X-ray emission
      spectroscopy (XES) for determining the cation site occupation. As a test system
      we use spinel phase CoxMn3-xO4 nanoparticles contaminated with CoO phases because
      Co and Mn can occupy all cation sites and the impurity simulates typical products
      of oxide syntheses. We take advantage of the spin and oxidation state sensitive
      Kbeta1,3 peak obtained using XES and demonstrate that XES is a powerful and
      reliable technique for determining site occupation in ternary spinel systems.
      Comparison between the extended X-ray absorption fine structure (EXAFS) and XES
      techniques reveals that XES provides not only the site occupation information as
      EXAFS, but also additional information on the oxidation states of the cations at
      each site. We show that the error for EXAFS can be as high as 35% which makes the
      results obtained ambiguous for certain stoichiometries, whereas for XES, the
      error determined is consistently smaller than 10%. Thus, we conclude that XES is
      a superior and a far more accurate method than XAS in extracting cation site
      occupation in spinel crystal structures.

PMID- 30238098
TI  - Biomimetic synthesis of 2-substituted N-heterocycle alkaloids by one-pot
      hydrolysis, transamination and decarboxylative Mannich reaction.
AB  - Heterocycles based on piperidine and pyrrolidine are key moieties in natural
      products and pharmaceutically active molecules. A novel multi-enzymatic approach
      based on the combination of a lipase with an alpha,omega-diamine transaminase is
      reported, opening up the synthesis, isolation and characterisation of a broad
      range of 2-substituted N-heterocycle alkaloids.

PMID- 30238099
TI  - Unimolecular decomposition kinetics of the stabilised Criegee intermediates CH2OO
      and CD2OO.
AB  - Decomposition kinetics of stabilised CH2OO and CD2OO Criegee intermediates have
      been investigated as a function of temperature (450-650 K) and pressure (2-350
      Torr) using flash photolysis coupled with time-resolved cavity-enhanced broadband
      UV absorption spectroscopy. Decomposition of CD2OO was observed to be faster than
      CH2OO under equivalent conditions. Production of OH radicals following CH2OO
      decomposition was also monitored using flash photolysis with laser-induced
      fluorescence (LIF), with results indicating direct production of OH in the v = 0
      and v = 1 states in low yields. Master equation calculations performed using the
      Master Equation Solver for Multi-Energy well Reactions (MESMER) enabled fitting
      of the barriers for the decomposition of CH2OO and CD2OO to the experimental
      data. Parameterisations of the decomposition rate coefficients, calculated by
      MESMER, are provided for use in atmospheric models and implications of the
      results are discussed. For CH2OO, the MESMER fits require an increase in the
      calculated barrier height from 78.2 kJ mol-1 to 81.8 kJ mol-1 using a temperature
      dependent exponential down model for collisional energy transfer with DeltaEdown
      = 32.6(T/298 K)1.7 cm-1 in He. The low- and high-pressure limit rate coefficients
      are k1,0 = 3.2 * 10-4(T/298)-5.81exp(-12 770/T) cm3 s-1 and k1,infinity = 1.4 *
      1013(T/298)0.06exp(-10 010/T) s-1, with median uncertainty of ~12% over the range
      of experimental conditions used here. Extrapolation to atmospheric conditions
      yields k1(298 K, 760 Torr) = 1.1+1.5-1.1 * 10-3 s-1. For CD2OO, MESMER
      calculations result in DeltaEdown = 39.6(T/298 K)1.3 cm-1 in He and a small
      decrease in the calculated barrier to decomposition from 81.0 kJ mol-1 to 80.1 kJ
      mol-1. The fitted rate coefficients for CD2OO are k2,0 = 5.2 * 10-5(T/298)
      5.28exp(-11 610/T) cm3 s-1 and k2,infinity = 1.2 * 1013(T/298)0.06exp(-9800/T) s
      1, with overall error of ~6% over the present range of temperature and pressure.
      The extrapolated k2(298 K, 760 Torr) = 5.5+9.2-5.5 * 10-3 s-1. The master
      equation calculations for CH2OO indicate decomposition yields of 63.7% for H2 +
      CO2, 36.0% for H2O + CO and 0.3% for OH + HCO with no significant dependence on
      temperature between 400 and 1200 K or pressure between 1 and 3000 Torr.

PMID- 30238100
TI  - Alignment of 17O-enriched water-endofullerene H2O@C60 in a liquid crystal matrix.
AB  - We present a 17O and 1H NMR study of molecular endofullerene H2O@C60 dissolved in
      the nematic liquid crystal N-(4-methoxybenzylidene)-4-butylaniline (MBBA). The
      17O NMR peak is split into five components by the 17O residual quadrupolar
      coupling, each of which is split into a triplet by the 1H-17O residual dipolar
      coupling and scalar coupling. The splittings are analysed in terms of the partial
      alignment of the encapsulated water molecules. Order parameters describing the
      alignment are estimated. It is found that the preferential orientation of the
      endohedral water molecule has the molecular plane perpendicular to the liquid
      crystal director.

PMID- 30238101
TI  - Allosteric Na+-binding site modulates CXCR4 activation.
AB  - G protein-coupled receptors (GPCRs) control most cellular communications with the
      environment and are the largest protein family of drug targets. As strictly
      regulated molecular machines, profound comprehension of their activation
      mechanism is expected to significantly facilitate structure-based drug design.
      This study provides atomistic-level description of the activation dynamics of the
      C-X-C chemokine receptor type 4 (CXCR4), a class A GPCR and important drug
      target. Using molecular dynamics and enhanced sampling, we demonstrate how
      mutations and protonation of conserved residues trigger activation through
      microswitches at the receptor core, while sodium ion - a known allosteric
      modulator - inhibits it. The findings point to a conserved mechanism of
      activation and the allosteric modulation by sodium in the chemokine receptor
      family. From the technical aspect, the enhanced sampling protocol effectively
      samples receptor conformational changes toward activation, and differentiates
      three variants of the receptor by their basal activity. This work provides
      structural basis and a powerful in silico tool for CXCR4 agonist design.

PMID- 30238102
TI  - Organocatalysis and catalyst aggregation: a study using the asymmetric synthesis
      of benzofuranones as a test reaction.
AB  - A common problem encountered in enantioselective organocatalysis is the
      aggregation of the catalyst, which can result in a relevant decrease of the
      efficiency and selectivity of the process. In the asymmetric synthesis of chiral
      benzofuranones, recently reported by us, we noted a remarkable increase of the
      reaction yield upon the addition of one of the reagents in a portionwise manner
      rather than in a single addition. We investigated this phenomenon by several
      experimental techniques such as 1D and 2D NMR experiments, UV-Vis spectroscopy,
      circular dichroism and dynamic light scattering. In addition, we studied the
      kinetic profile of this reaction using a simple numerical model and carried out
      in silico investigations. All these different approaches point to the conclusion
      that in the reaction medium a supramolecular polymerization/aggregation
      phenomenon, based on weak interactions, occurs and such a process is promoted by
      a quinone, which is one of the reagents of the benzofuranone synthesis. The
      portionwise mode of addition is a known strategy which can improve the
      performance of many synthetic procedures and this strategy is commonly adopted on
      account of empirical experience. However, our results provide an explanation,
      based on a chemical kinetic model, of the reason why the portionwise addition
      affects in such a dramatic way the yield of the benzofuranone synthesis catalyzed
      by Cinchona alkaloids.

PMID- 30238103
TI  - Curve crossing in a manifold of coupled electronic states: direct quantum
      dynamics simulations of formamide.
AB  - Quantum dynamics simulations are an important tool to evaluate molecular
      behaviour including the, often key, quantum nature of the system. In this paper
      we present an algorithm that is able to simulate the time evolution of a molecule
      after photo-excitation into a manifold of states. The direct dynamics variational
      multi-configurational Gaussian (DD-vMCG) method circumvents the computational
      bottleneck problems of traditional grid-based methods by computing the potential
      energy functions on-the-fly, i.e. only where required. Unlike other commonly used
      direct dynamics methods, DD-vMCG is fully quantum mechanical. Here, the method is
      combined with a novel on-the-fly diabatisation scheme to simulate the short-time
      dynamics of the key molecule formamide and its acid analogue formimidic acid.
      This is a challenging test system due to the nature and large number of excited
      states, and eight coupled states are included in the calculations. It is shown
      that the method is able to provide unbiased information on the product channels
      open after excitation at different energies and demonstrates the potential to be
      a practical scheme, limited mainly by the quality of the quantum chemistry used
      to describe the excited states.

PMID- 30238104
TI  - Optical properties of quadrupolar and bi-quadrupolar dyes: intra and inter
      chromophoric interactions.
AB  - In this work we present the synthesis, characterization and theoretical
      investigation of three boron-difluoride-curcuminoid derivatives and their
      covalent homodimers chemically linked through a polymethylenic chain. Low-lying
      electronic excited states and photophysical properties of the monomeric species
      have been described as the convolution of different donor-acceptor intramolecular
      excitations. Covalent dimers in solution can present open or folded structural
      conformations. Analysis of absorption profiles and computational results allow to
      identify the factors that control the relative stability of the two forms and
      rationalize its dependence with the solvent polarity. Interestingly, the strong
      electronic coupling in the folded forms results in low-lying excitations with
      sizable mixings of intra- and inter-chromophoric contributions, which cannot be
      described by means of the Kasha model of interacting chromophores. Our study
      demonstrates how decomposition of the computed excitations in terms of diabatic
      states can be extremely valuable in order to identify and quantify the nature of
      electronic transitions in the presence of several electron donor and acceptor
      fragments.

PMID- 30238105
TI  - Substrate-affected lattice structural evolution in compressed monolayer ReS2.
AB  - At ambient conditions, the lattice structure of supported ultrathin transition
      metal dichalcogenides (TMDs) can be effectively modified by a substrate. When
      compressed, the effect of substrate is far from settled. In this study, the
      effects of an Si substrate on the lattice structures of compressed monolayer and
      multilayer ReS2 were investigated by performing high-pressure Raman measurements
      and first-principle calculations. Our results revealed substrate-affected strain
      in compressed monolayer ReS2, which resulted in a distorted unit with S atoms
      sliding within a single layer. This was evidenced by the split of the Ag-5 mode
      above 1.7 GPa. However, unlike that of the monolayer ReS2, the Ag-5 mode of
      multilayer ReS2 remained symmetric up to 4.2 GPa, which can be due to weaker
      substrate-affected strain in compressed multilayer ReS2 when compared with that
      in the monolayer ReS2. The noticeably different high-pressure responses between
      multilayer ReS2 and monolayer ReS2 can be due to the effect of interlayer
      interactions, and the split of the Ag-5 mode provides a clear indication of the
      prominent strain in compressed supported ReS2.

PMID- 30238106
TI  - Conformation-dependent phosphorescence emission of individual mononuclear
      ruthenium-(ii)-bis-terpyridine complexes.
AB  - The potential of supramolecular transition metal coordination complexes to form
      robust, long-living, radiative charge transfer states makes this class of triplet
      state emitters ideal candidates for application as photosensitizes or in photonic
      devices. Antenna-enhanced phosphorescence experiments on single Ru2+-bis
      terpyridine complexes incorporated into a thin PMMA film show that
      phosphorescence emission spectra can exhibit shifts depending on the local
      environment [J. F. Herrmann, P. S. Popp, A. Winter, U. S. Schubert and C.
      Hoppener, ACS Photonics, 2016, 3, 1897-1906]. Here, we demonstrate that the
      environmentally altered spectral properties of individual dual-luminescent Ru2+
      bis-terpyridine complexes in PMMA and acetonitrile can be reproduced by DFT-based
      vibrationally resolved Franck-Condon spectra, if the phosphorescent emission of
      different molecular conformations is taken into account. Furthermore, we
      demonstrate that the triplet emission of these complexes occurs from a metal-to
      ligand charge transfer (MLCT) state.

PMID- 30238107
TI  - Study of volume and surface plasmons in small silicon-hydrogen nanoclusters using
      the GW method.
AB  - Numerical calculations of surface and volume plasma excitations in silicon
      hydrogen nanoclusters in the range Si10-Si60 and Si3H8-Si64H56 (size range 4-13.5
      A) are performed within the GW approximation. Some nanocluster structures were
      obtained using the evolutionary algorithm, and others were taken from the
      database. The applied method shows the results to be consistent with the
      experiments (except plasmaron artifacts) for fullerene clusters and bulk silicon
      along with sufficient sensitivity to allow investigatation of the effect of the
      cluster structure and size on the specific properties of plasma excitations.
      Detailed experimental data on plasmons are mainly available for silicon clusters
      of 30 A and more, in which plasmon properties do not differ much from those in
      bulk silicon. Calculations show that in the studied nanoclusters the situation
      changes noticeably. The structure and surface of the cluster begin to affect the
      plasmons in a key way, structures close in size and composition may have markedly
      different plasmon properties. Passivation of silicon dangling bonds on the
      cluster surface changes frequency and damping of plasmons, making the surface and
      volume plasmons clearly distinguishable even in small nanoclusters as Si3H8.

PMID- 30238108
TI  - Sea cucumber mimicking bacterial cellulose composite hydrogel with ionic strength
      sensitive mechanical adaptivity.
AB  - A novel strategy for fabricating sea cucumber-mimicking hydrogels composed of a
      bacterial cellulose matrix and a stimuli-responsive polymer is presented. This
      mechanically adaptive hydrogel shows a unique reversible stiffness change in
      response to its ionic strength without any significant volume changes.

PMID- 30238109
TI  - Exploring the influence of natural cosolvents on the free energy and
      conformational landscape of filamentous actin and microtubules.
AB  - Actin and tubulin, the main components of the cytoskeleton, are responsible for
      many different cellular functions and can be found in nearly all eukaryotic
      cells. The formation of filamentous actin (F-actin) as well as microtubules
      depends strongly on environmental and solution conditions. The self-assembly of
      both, actin and tubulin, has been found to be among the most pressure sensitive
      process in vivo. Here, we explored the effects of various types of natural
      cosolvents, such as urea and the osmolyte trimethylamine-N-oxide (TMAO), on the
      temperature- and pressure-dependent stability of their polymeric states, F-actin
      and microtubules. Accumulation of TMAO by deep-sea animals is proposed to protect
      against destabilizing effects of pressure. The pressure and temperature of
      unfolding as well as associated enthalpy and volume changes have been determined
      using Fourier-transform infrared spectroscopy, covering a wide range of pressures
      and temperatures, ranging from 1 bar to 11 kbar and from 20 to 90  degrees C,
      respectively. Complementary thermodynamic measurements have been carried out
      using differential scanning and pressure perturbation calorimetry. The results
      obtained helped us explore the effect of the cellular milieu on the limitations
      of the pressure stability of cytoskeletal assemblies. Conversely to urea, the
      pressure stability of both polymers increases dramatically in the presence of
      TMAO, counteracting detrimental effects of both, urea and pressure.

PMID- 30238110
TI  - Self-healing, stretchable and robust interpenetrating network hydrogels.
AB  - A self-healable stretchable hydrogel system that can be readily synthesized while
      also possessing robust compressive strength has immense potential for
      regenerative medicine. Herein, we have explored the addition of commercially
      available unfunctionalized polysaccharides as a route to synthesize self-healing,
      stretchable poly(ethylene glycol) (PEG) interpenetrating networks (IPNs) as
      extracellular matrix (ECM) mimics. The introduction of self-healing and
      stretchable properties has been achieved while maintaining the robust mechanical
      strength of the orginal, single network PEG-only hydrogels (ultimate compressive
      stress up to 2.4 MPa). This has been accomplished without the need for
      complicated and expensive functionalization of the natural polymers, enhancing
      the translational applicability of these new biomaterials.

PMID- 30238111
TI  - Enhanced anti-obesity effects of bacterial cellulose combined with konjac
      glucomannan in high-fat diet-fed C57BL/6J mice.
AB  - This study aimed to investigate the effects of supplementation with bacterial
      cellulose (BC), konjac glucomannan (KGM) and combined BC/KGM fiber on high-fat
      (HF)-diet-induced obesity in C57BL/6J mice. The results showed that combined
      supplementation with BC/KGM in HF-fed mice was more efficient in reducing body
      weight, lowing serum lipid profiles and suppressing insulin resistance than
      single supplementation with BC or KGM. Moreover, supplementation with combined
      BC/KGM fiber more efficiently alleviated HF-diet-induced liver injury by
      decreasing hepatic steatosis in comparison with supplementation with BC or KGM
      alone. Furthermore, supplementation with combined BC/KGM fiber in HF-fed mice had
      a more positive effect on obesity-associated hepatic inflammation by reducing
      levels of TNF-alpha and IL-6 and suppressing the protein expression of Nrf-2/ARE
      in comparison with supplementation with BC or KGM alone. Consumption of these
      dietary fibers, especially mixed BC/KGM, resulted in an improved antioxidant
      defense system and reduced lipid peroxidation in the liver by increasing the
      activity of antioxidant enzymes and reducing the formation of MDA in the liver.
      Moreover, supplementation with these fibers regulated the levels of leptin and
      adiponectin and inhibited the protein expression of PPARgamma by reducing the
      size of cells in the adipose tissue of HF diet-fed mice. Therefore, fiber
      supplementation (especially with combined BC/KGM) efficiently inhibited HF
      induced obesity in mice by reducing insulin resistance, liver injury and
      inflammation, enhancing the antioxidant defense system and regulating the
      secretion of adipocytokines and adipogenesis-associated proteins.

PMID- 30238112
TI  - Reactivity and properties of bis(chlorodifluoroacetyl) peroxide generated in situ
      from chlorodifluoroacetic anhydride for chlorodifluoromethylation reactions.
AB  - We developed a practical chlorodifluoromethylation reaction mediated by diacyl
      peroxide generated in situ from chlorodifluoroacetic anhydride. Allylic and amino
      chlorodifluoromethylations of alkenes proceeded well with the combination of this
      reagent, Cu(ii) catalyst and a pyridine additive. Carbo- and aromatic
      chlorodifluoromethylations proceeded under metal-free conditions.

PMID- 30238113
TI  - Phenoxide chelated Ir(iii) N-heterocyclic carbene complexes: synthesis,
      characterization, and evaluation of their in vitro anticancer activity.
AB  - Twelve novel half-sandwich IrIII-NHC complexes [(eta5-Cpx)Ir(C^O)Cl] were
      synthesized and characterized. These complexes showed higher cytotoxic activity
      toward A549 cells and HeLa cells than cisplatin. An increase in the number of
      contained phenyl groups was related to better anticancer activity. The reaction
      of complexes with nucleobases 9-MeA, nucleobases 9-EtG, plasmid DNA and CT-DNA
      showed no significant effects. These complexes captured hydrogen from NADH and
      converted it to NAD+, which produced the reactive oxygen species (ROS). ROS led
      to a decrease in the mitochondrial membrane potential and lysosomal damage,
      finally inducing apoptosis.

PMID- 30238114
TI  - Correction: Driving dynamic colloidal assembly using eccentric self-propelled
      colloids.
AB  - Correction for 'Driving dynamic colloidal assembly using eccentric self-propelled
      colloids' by Zhan Ma et al., Soft Matter, 2017, 13, 8940-8946.

PMID- 30238115
TI  - A naphthalene-based fluorescent probe with a large Stokes shift for mitochondrial
      pH imaging.
AB  - A mitochondrial-targeted pH fluorescent probe 4-(2-(6-hydroxynaphthalen-2
      yl)vinyl)-1-methylpyridin-1-ium was facilely synthesized via the carbon-carbon
      double bond bridging of 6-hydroxy-2-naphthaldehyde and 1,4-dimethylpyridinium
      iodide salt. The probe exhibited remarkable pH-dependent behavior in the linear
      range of 7.60-10.00, with a pKa value of 8.85 +/- 0.04 near mitochondrial pH. A
      significantly large Stokes shift of 196 nm was obtained, which reduces the
      interference of excitation light. Application of the probe in live HepG2 cells
      indicated that the probe had excellent mitochondrial targeting ability and was
      successfully used to visualize mitochondrial pH fluctuations in live cells.

PMID- 30238116
TI  - A fishhook probe-based rolling circle amplification (FP-RCA) assay for efficient
      isolation and detection of microRNA without total RNA extraction.
AB  - MicroRNA (miRNA) analysis has vital significance as a potential biomarker in
      clinical diagnosis and cancer research. In this study, a simple and practical
      technique was proposed for the detection of microRNAs from cell lysates based on
      fishhook probe-mediated rolling circle amplification (RCA) and fluorescence
      imaging with a smartphone. Compared with reported methods related to miRNA
      detection, this method mainly focused on simplicity, low cost and portability.
      Fishhook probes were designed and immobilized on the surface of streptavidin
      coated magnetic beads for effectively recognizing and capturing target miRNAs,
      thus achieving simple and selective separation from the sample matrix. Moreover,
      the captured miRNAs initiated and transferred RCA reaction into solution, thus
      making the heterogeneous separation and homogeneous amplification reactions
      compatible. Excess circular probes as well as other nucleic acids were removed by
      two-step magnetic separation, minimizing nonspecific amplification and background
      signal. Using magnetic separation, high specificity was obtained even for one
      base mismatch strand. Moreover, the detection of miR-21 in cell lysates was
      performed without total RNA extraction. The fishhook probe-based rolling circle
      amplification (FP-RCA) assay integrated isolation and detection of miRNAs into a
      compact process, which was simple and effective without the need for bulky and
      expensive equipment such as centrifuge, thermal cycler and fluorescent microscope
      except for a blue light source device and a smartphone camera. Our study may
      provide a low-cost and reliable platform for miRNA detection and related
      research.

PMID- 30238117
TI  - Excited state dynamics and time-resolved photoelectron spectroscopy of para
      xylylene.
AB  - We investigated the excited-state dynamics of para-xylylene using a combination
      of field-induced surface hopping (FISH) simulations and time-resolved ionisation
      experiments. Our simulations predict an ultrafast decay of the initially excited
      bright state (S2/S3) to the S1 state on a sub-100 fs time scale, followed by
      return to the ground state within ~1 ps. This is accompanied by a transient
      change of the biradical character of the molecule, as monitored by calculating
      natural orbital occupation numbers. Specifically, the initially low biradicality
      is increased by electronic excitation as well as by vibrational activation.
      Experimentally, para-xylylene was generated by pyrolysis from [2,2]paracyclophane
      and excited with 266 nm radiation into the S2/S3 bright state. The subsequent
      dynamics were followed using ionisation as the probe step, with both mass spectra
      and photoelectron spectra recorded as a function of pump-probe delay. The
      observed decay of photoelectron and photoion intensities closely matches the
      theoretical predictions and is consistent with the sequential mechanism found in
      the simulations. This mechanism exhibits characteristic signatures in both time
      resolved mass and photoelectron spectra, in particular in the appearance of
      fragment ions that are exclusively generated from the S1 state. This allows for a
      separation of the S2 and S1 dynamics in the photoelectron and mass spectra. An
      excellent agreement between the observed and the simulated ion signal is
      observed.

PMID- 30238118
TI  - Catalyst free hydrazone ligation for protein labeling and modification using
      electron-deficient benzaldehyde reagents.
AB  - Bioorthogonal reactions have emerged as valuable tools for site-specific protein
      labeling and modification in vitro and in vivo. Hydrazone and oxime ligation has
      recently attracted considerable attention for wide applications in the
      conjugation of biomolecules. However, this kind of reaction has suffered from
      slow kinetics under physiological conditions and toxicity or complications of the
      reaction system due to catalysts. In this work we have developed an electron
      deficient benzaldehyde reagent, which can be easily equipped with various types
      of bio-functional molecules for catalyst-free hydrazone ligation. The reagent can
      be equipped with not only small molecules such as fluorescence dyes or drugs, but
      also macromolecules like PEG. These can be precisely ligated to the C-terminus of
      proteins by an efficient hydrazone reaction at neutral pH and room temperature.
      The new reagent based catalyst-free hydrazone ligation provides a practical
      approach for the site specific modification of proteins.

PMID- 30238119
TI  - Efficient construction of tetrahydroquinolines via fluorinated alcohol mediated
      cascade [1,5]-hydride transfer/cyclization.
AB  - An environmentally benign cascade redox-neutral process was developed for the
      efficient construction of pharmaceutically significant spirocyclic tetrahydro
      quinolines via a 3-step cascade Knoevenagel condensation/[1,5]-hydride
      transfer/cyclization, which features green and additive-free conditions, wide
      substrate scope, and high step- and atom-economy.

PMID- 30238127
TI  - Role of Monocytes in the Pathogenesis of Dengue.
AB  - Diseases caused by dengue virus (DENV) are a major public health problem
      worldwide, considered one of the infections with more prevalence in tropical and
      subtropical zones of the world. Despite the intense research in the pathogenesis
      of DENV, this feature is not well understood. One of the main target cells for
      DENV infection is monocytes; these phagocytes can play a dual role, since they
      are essential to control viremia, but they also participate in the induction of
      tissue damage during DENV infection. Monocytes produce different pro-inflammatory
      cytokines and chemokines in response to infection, and also mediate endothelial
      damage. In peripheral blood, monocytes can be divided into three different
      subpopulations, namely classical, intermediate and non-classical, which differ in
      frequency, cytokine production, among others. Studies in the last years suggest
      that non-classical monocytes have higher affinity for microvasculature
      endothelium compared to other type of monocytes, which implies that they could be
      more involved in the increase of endothelial permeability observed during DENV
      infection. This review provides a general view of the role of monocytes and their
      subpopulations in DENV pathogenesis and its effect in viral replication. Finally,
      the potential contribution of these phagocytes in the alterations of endothelial
      permeability is discussed.

PMID- 30238128
TI  - Effects of Zn and Ti Nanoparticles on the Survival and Growth of Sclerophrys
      arabica Tadpoles in a Two Level Trophic System.
AB  - Under natural conditions pollutants rarely affect only a single trophic level.
      This study investigated the effects of titanium dioxide (Ti-NPs) and zinc oxide
      (Zn-NPs) nanoparticles on survival and growth of Sclerophrys arabica tadpoles
      exposed directly in water, indirectly through their food source (decomposing
      leaves), or a combination of both. Zn-NPs did not cause significant mortality.
      The LC50 for tadpoles exposed to Ti-NPs directly was 74.9 ug/L (95% CI 16.6-338.7
      ug/L) and 18.3 ug/L (95% CI 6.5-51.9 ug/L) for tadpoles exposed directly and with
      pre-treated leaves. Tadpoles fed only pre-exposed food did not show significant
      mortality. Exposure route also affected growth. On average the tadpoles with the
      lowest body mass were found in the water-only exposures, followed by the water
      and leaf treatments. However, the tadpoles with the greatest body mass were in
      the treatments fed with leaves pretreated with Ti-NPs. This suggests that the NPs
      made their contents more available to the tadpoles.

PMID- 30238129
TI  - [Anesthesia in patients with NBIA : Neurodegeneration with brain iron
      accumulation].
AB  - BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) forms a group
      of rare hereditary diseases with rapid neurodegenerative progression due to an
      abnormal accumulation of iron in the basal ganglia. This causes extrapyramidal
      symptoms as well as dystonia and mental retardation. The most common form of NBIA
      is pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden
      Spatz syndrome). There are multiple anesthesiological challenges with great
      implications for the clinical routine, particularly regarding the preparation for
      general anesthesia and the premedication visits. As with other orphan diseases,
      the available recommendations are mainly based on case reports. OBJECTIVE AND
      METHODS: This article gives a short overview of complications associated with
      NBIA pertaining to general anesthesia. This includes anesthesia-relevant clinical
      symptoms and perioperative management. The published literature and case reports
      (available on PubMed) were reviewed to extract a set of recommendations. RESULTS:
      So far only a few reports have included the anesthesia management of NBIA
      patients. Most of them refer to PKAN as the predominant type (50% of cases).
      Recommendations were found on www.orphananesthesia.eu and consensus guidelines on
      PKAN in general. In particular, dystonia-related restrictions in the
      maxillofacial area can complicate airway management and cause difficulties with
      respect to intubation. Furthermore, local or regional anesthesia as the sole
      anesthesia technique is not eligible/viable due to the reduced compliance of the
      patient. Special attention should be paid to a timely premedication visit and
      evaluation to ensure sufficient time to safely plan and prepare the anesthetic
      procedure. CONCLUSION: The handling of NBIA patients requires good preparation,
      including an interdisciplinary team and customized time management. In principle,
      both general anesthesia as a balanced method and total intravenous anesthesia
      (TIVA) seem to be possible/viable options. The main focus is on airway
      management. Even after brief sedation in the context of diagnostic measures, the
      patient should be monitored for longer than usual.

PMID- 30238131
TI  - N-Methyl D-aspartate receptor subunit signaling in fear extinction.
AB  - N-Methyl D-aspartate receptors (NMDAR) are central mediators of glutamate actions
      underlying learning and memory processes including those required for extinction
      of fear and fear-related behaviors. Consistent with this view, in animal models,
      antagonists of NMDAR typically impair fear extinction, whereas partial agonists
      have facilitating effects. Promoting NMDAR function has thus been recognized as a
      promising strategy towards reduction of fear symptoms in patients suffering from
      anxiety disorders and post-traumatic disorder (PTSD). Nevertheless, application
      of these drugs in clinical trials has proved of limited utility. Here we
      summarize recent advances in our knowledge of NMDAR pharmacology relevant for
      fear extinction, focusing on molecular, cellular, and circuit aspects of NMDAR
      function as they relate to fear extinction at the level of behavior and
      cognition. We also discuss how these advances from animal models might help to
      understand and overcome the limitations of existing approaches in human anxiety
      disorders and how novel, more specific, and personalized approaches might help
      advance future therapeutic strategies.

PMID- 30238132
TI  - [Shared decision-making in prostate cancer patients].
AB  - BACKGROUND: Shared decision-making (SDM) is becoming increasingly important in
      medical care. The relevance of SDM after diagnosis is especially noticeable in
      the care of prostate cancer patients, since affected patients can choose from
      different treatment strategies. OBJECTIVES: What are the experiences of patients
      regarding SDM in the treatment of prostate cancer? METHODS: Interviews with
      qualitative-exploratory study design were carried out and evaluated. The
      interviews were recorded with the help of audio tapes and literally transcribed
      and pseudonymized based on Kuckartz. The evaluation was done by theoretical
      coding according to Glaser and Strauss. This enabled the development of an object
      based theory of interview data. RESULTS: The study shows that all interviewees
      experienced SDM and were able to reflect on this process. The interviewed
      patients had a high level of information regarding their disease status and
      treatment options, in which individual preferences played a key role. Some
      patients saw potential for optimization in the physician-patient conversation,
      taking personal preferences into account. CONCLUSIONS: Patients are not limited
      to medical information only, but have taken an active role in their treatment
      decision. Many of the participants consulted several physicians to obtain second
      opinions. Since the survey focuses on the patients' perspective, it remains
      unclear whether a joint exchange of information and decision-making has taken
      place from a medical point of view.

PMID- 30238130
TI  - Cannabidiol modulation of antinociceptive tolerance to Delta9
      tetrahydrocannabinol.
AB  - RATIONALE: Humans typically self-administer cannabidiol (CBD) and delta-9
      tetrahydrocannabinol (THC) together repeatedly (as in cannabis, cannabis extract,
      or Sativex(r)) to relieve pain. It has been suggested that one benefit of the
      drug combination may be decreased tolerance development. OBJECTIVE: The present
      study compared the development of tolerance to the antinociceptive effects of THC
      given alone versus combined with CBD, in rats. METHODS: THC dose-effect curves on
      tail withdrawal and paw pressure tests were obtained before and after twice-daily
      treatment with vehicle or CBD (10 mg/kg), plus vehicle or THC (3.6 mg/kg females;
      9.3 mg/kg males) for 4 days. RESULTS: On the first day, THC was more potent in
      females than males on both nociceptive tests. From pre- to post-chronic (day 1 to
      day 6), THC potency on the tail withdrawal test decreased more in females than
      males, and rats that had been treated with CBD + THC repeatedly showed greater
      rightward/downward shifts of the THC dose-effect curve than rats that had been
      treated with THC alone. Analysis of blood samples taken after day 6 testing
      showed that serum THC levels were higher in CBD + THC-treated females than in
      vehicle + THC-treated females, and THC's active metabolite 11-OH-THC and its
      inactive metabolite THC-COOH were lower in CBD + THC-treated rats than in vehicle
      + THC-treated rats of both sexes. CBD also increased serum levels of the active
      metabolite cannabinol in both sexes. CONCLUSION: The decrease in THC's
      antinociceptive effects after repeated CBD exposure may be due to CBD-induced
      inhibition of THC metabolism, and/or antagonism of THC effects that emerges with
      repeated CBD treatment.

PMID- 30238133
TI  - Role of peroxisome proliferator-activated receptor alpha (PPARalpha) and
      PPARalpha-mediated species differences in triclosan-induced liver toxicity.
AB  - Triclosan, a widely used broad spectrum anti-bacterial agent, is hepatotoxic in
      rodents and exhibits differential effects on mouse and human peroxisome
      proliferator-activated receptor alpha (PPARalpha) in vitro; however, the
      mechanism underlying triclosan-induced liver toxicity has not been elucidated.
      This study examined the role of mouse and human PPARalpha in triclosan-induced
      liver toxicity by comparing the effects between wild-type and PPARalpha-humanized
      mice. Female mice of each genotype received dermal applications of 0, 58, or 125
      mg triclosan/kg body weight daily for 13 weeks. Following the treatment,
      triclosan caused an increase in liver weight and relative liver weight only in
      wild-type mice. The expression levels of PPARalpha target genes cytochrome P450
      4A and acyl-coenzyme A oxidase 1 were increased in livers of both wild-type and
      PPARalpha-humanized mice, indicating that triclosan activated PPARalpha.
      Triclosan also elevated the expression levels of peroxisomal membrane protein
      PMP70 and catalase in the livers of both genotypes, suggesting that triclosan
      promoted the production of hepatocyte peroxisomes. There was an enhanced
      expression of cyclin D1, c-myc, proliferating cell nuclear antigen, and Ki67, and
      a higher percentage of BrdU-labeled hepatocytes in wild-type mice, but not in
      PPARalpha-humanized mice, demonstrating triclosan-activated PPARalpha had
      differential effects on the hepatocyte proliferation. These findings imply that
      the differential effects of triclosan-activated PPARalpha on cell proliferation
      may play a role in the species differences in triclosan-induced liver toxicity.

PMID- 30238136
TI  - Letter Regarding: "Evaluation of Early Left Ventricular Dysfunction in Patients
      with Duchenne Muscular Dystrophy Using Two-Dimensional Speckle Tracking
      Echocardiography and Tissue Doppler Imaging," Cho et al., Pediatric Cardiology
      ePub July 2018.

PMID- 30238135
TI  - Resveratrol: an effective pharmacological agent to prevent inflammation-induced
      atrial fibrillation?

PMID- 30238137
TI  - Extubation in the Operating Room After Fontan Procedure: Does It Make a
      Difference?
AB  - Early extubation appears to have beneficial effects on the Fontan circulation.
      The goal of this study was to assess the impact of extubation on the operating
      table in comparison with extubation during the first hours after Fontan operation
      (FO) on the early postoperative course. Between 2013 and 2016, 114 children with
      a single ventricle heart malformations (mean age, 3.8 +/- 2.3 years) underwent
      FO: 60 patients were extubated in the operating room (ORE) and 54 in the
      intensive care unit (ICUE) in the median time of 195 min (range 30-515 min) after
      procedure. Pre-, peri-, and postoperative records were retrospectively analyzed.
      The hospital survival rate was 100%. One patient from the ORE group needed an
      immediate reintubation because of laryngospasm. The ORE group showed lower heart
      rate (106.5 vs. 120.3 bpm; p < 0.001) and lower central venous pressure (10.4 vs.
      11.4 mmHg; p = 0.001) than patients in the ICUE group within the first 24 h after
      FO, as well as higher systolic blood pressure within 7 h after operation (88.6 +/
      2.5 vs. 85.6 +/- 2.6 mmHg; p = 0.036). The ORE children manifested significantly
      less pleural effusions during 48 h after FO (38.0 vs. 49.5 ml/kg; p = 0.004),
      received less intravenous fluid administration within 24 h after FO (54.1 vs.
      73.8 ml/kg; p = 0.019), less inotropic support (9.8 vs. 12.8 h of dopamine; p =
      0.033), and less antibiotics (4.7 vs. 5.8 days; p = 0.037). ICUE children
      manifested metabolic acidosis more frequently than the ORE group 3-4 h after FO
      (p < 0.05). Immediate extubation after FO in comparison with extubation in the
      ICU appears to be associated with improved hemodynamics and reduced application
      of therapeutic interventions in the postoperative course.

PMID- 30238134
TI  - [Telemonitoring and pulmonary artery pressure-guided treatment of heart failure].
AB  - Heart failure (HF) is an emerging epidemic associated with significant morbidity
      and mortality, impaired quality of life and high healthcare costs. Despite major
      advances in pharmacological and device-based therapies, mortality and morbidity
      have remained high after an index hospitalization for acute cardiac
      decompensation (ACD). Randomized trials evaluating various forms of noninvasive
      telemonitoring failed to improve rehospitalization rates in such patients,
      possibly due to lack of sensitivity of clinical signs and symptoms as early
      indicators of HF. Among different implantable monitoring devices, wireless remote
      monitoring of the pulmonary artery pressure (PAP) with the CardioMEMSTM sensor
      (Abbott, Sylmar, CA, USA) has been shown to be safe and clinically effective in
      the USA. The patients showed substantial reductions in hospital admissions for
      ACD, irrespective of left ventricular pump function, because PAP-guided HF
      management facilitates timely recognition of incipient ACD and appropriate
      modification of medical treatment before hospitalization becomes unavoidable.
      These encouraging results have also stimulated evaluation of this novel
      technology outside the USA. Studies are also underway in Europe and European HF
      guidelines recommend considering implantation of a CardioMEMSTM sensor in high
      risk patients (class IIb-B). More technologically refined implantable hemodynamic
      monitoring systems allowing, for example, left atrial pressure measurements, are
      under development. Promising novel approaches to using information from such
      devices include continuous hemodynamic monitoring and patient self-management
      based on the pressure information. Thus, pressure-guided HF management is likely
      to further expand in the future and may help improve clinical outcomes also in
      high-risk HF populations.

PMID- 30238138
TI  - Bone metastases with multiple fluid-fluid levels from gastric cancer: a case
      report and review of literature.
AB  - We report the case of a 54-year-old man with 6 months of progressive sacral pain.
      Computed tomography showed a large osteolytic mass in the sacrum with multiple
      osteolytic foci in the ilium and lumbar spine. Magnetic resonance imaging
      revealed multiple fluid-fluid levels in the sacral lesion as well as in the
      lumbar foci. The multiple bone lesions were initially diagnosed as a primary
      sacral malignancy with multiple bone metastases. A biopsy of the sacral lesion
      under the guidance of computed tomography was performed and a metastatic
      adenocarcinoma from the stomach or lung was found pathologically. Finally, a
      gastric tubular adenocarcinoma was detected by endoscopic biopsy and the
      diagnosis of the patient was gastric cancer with uncommon multiple bone
      metastases.

PMID- 30238139
TI  - Radiologic evaluation of fracture healing.
AB  - While assessment of fracture healing is a common task for both orthopedic
      surgeons and radiologists, it remains challenging due to a lack of consensus on
      imaging and clinical criteria as well as the lack of a true gold standard.
      Further complicating this evaluation are the wide variations between patients,
      specific fracture sites, and fracture patterns. Research into the mechanical
      properties of bone and the process of bone healing has helped to guide the
      evaluation of fracture union. Development of standardized scoring systems and
      identification of specific radiologic signs have further clarified the
      radiologist's role in this process. This article reviews these scoring systems
      and signs with regard to the biomechanical basis of fracture healing. We present
      the utility and limitations of current techniques used to assess fracture union
      as well as newer methods and potential future directions for this field.

PMID- 30238140
TI  - Deciphering bacterial xylose metabolism and metabolic engineering of industrial
      microorganisms for use as efficient microbial cell factories.
AB  - The goal of sustainable production of biochemicals and biofuels has driven the
      engineering of microbial cell as factories that convert low-value substrates to
      high-value products. Xylose is the second most abundant sugar substrate in
      lignocellulosic hydrolysates. We analyzed the mechanisms of xylose metabolism
      using genome sequencing data of 492 industrially relevant bacterial species in
      the mini-review. The analysis revealed the xylose isomerase and Weimberg pathways
      as the major routes across diverse routes of bacterial xylose metabolism. In
      addition, we discuss recent developments in metabolic engineering of xylose
      metabolism in industrial microorganisms. Genome-scale analyses have revealed
      xylose pathway-specific flux landscapes. Overall, a comprehensive understanding
      of bacterial xylose metabolism could be useful for the feasible development of
      microbial cell factories.

PMID- 30238141
TI  - Comparison of conventional plating, PMA-qPCR, and flow cytometry for the
      determination of viable enterotoxigenic Escherichia coli along a gastrointestinal
      in vitro model.
AB  - Recent technological advances for bacterial viability assessment using molecular
      methods or flow cytometry can provide meaningful interest for the demarcation
      between live and dead microorganisms. Nonetheless, these methods have been
      scarcely applied to foodborne pathogens and never for directly assessing their
      viability within the human digestive environment. The purpose of this study was
      to compare two methods based on membrane integrity (propidium monoazide (PMA) q
      PCR and Live/Dead flow cytometry) and the classical plate-count method to
      determine the viability of a common foodborne pathogen, enterotoxigenic
      Escherichia coli (ETEC), during its transit trough simulated human
      gastrointestinal environment. Viable ETEC counts in the gastric and small
      intestinal compartments of the gastrointestinal TIM model indicated a consensus
      between the three tested methods (PMA-qPCR, flow cytometry, and plate counts). In
      a further step, flow cytometry analysis appeared as the preferred method to
      elucidate ETEC physiological states in the in vitro digestive environment by
      discriminating four subpopulations, while PMA-qPCR can only distinguish two. The
      defined viable/altered ETEC population was found during all in vitro digestions,
      but mainly in the gastric compartment. Being able to discriminate the particular
      physiological states of pathogenic microorganisms in the digestive environment is
      of high interest, because if some cells are not observable on culture media, they
      might keep their ability to express virulence functions.

PMID- 30238142
TI  - Baculovirus capsid display in vaccination schemes: effect of a previous immunity
      against the vector on the cytotoxic response to delivered antigens.
AB  - The baculovirus Autographa californica multiple nuclear polyhedrosis virus
      (AcMNPV) infects lepidopteran invertebrates as natural hosts, although it also
      has been used as display vector for vaccine development. In this work, we
      evaluated the effectiveness of repetitive doses of AcMNPV-based vectors on the
      cytotoxic immune response specific to the capsid-displayed heterologous antigen
      ovalbumin (OVA). Our results demonstrate that baculovirus vectors induce a
      boosting effect in the cytotoxic immune response to OVA, making possible to
      recover the levels obtained in the primary response. Moreover, mice preimmunized
      with wild-type baculovirus showed a complete lack of antigen-specific CD8
      cytotoxic T lymphocytes (CTLs) that may be related to the presence of antibodies
      directed to baculoviral surface proteins, particularly to GP64. However,
      baculovirus was able to induce the innate immune response in spite of a previous
      response against this vector, although some quantitative differences reflect a
      distinct activation of the immune cells in prime and boost. This is the first
      report in which the novel capsid display strategy is evaluated in prime-boost
      schemes to improve efficient CTL responses.

PMID- 30238143
TI  - Advancing metabolic engineering of Yarrowia lipolytica using the CRISPR/Cas
      system.
AB  - The oleaginous yeast Yarrowia lipolytica is widely used for the production of
      both bulk and fine chemicals, including organic acids, fatty acid-derived
      biofuels and chemicals, polyunsaturated fatty acids, single-cell proteins,
      terpenoids, and other valuable products. Consequently, it is becoming
      increasingly popular for metabolic engineering applications. Multiple gene
      manipulation tools including URA blast, Cre/LoxP, and transcription activator
      like effector nucleases (TALENs) have been developed for metabolic engineering in
      Y. lipolytica. However, the low efficiency and time-consuming procedures involved
      in these methods hamper further research. The emergence of the CRISPR/Cas system
      offers a potential solution for these problems due to its high efficiency, ease
      of operation, and time savings, which can significantly accelerate the genomic
      engineering of Y. lipolytica. In this review, we summarize the research progress
      on the development of CRISPR/Cas systems for Y. lipolytica, including Cas9
      proteins and sgRNA expression strategies, as well as gene knock-out/knock-in and
      repression/activation applications. Finally, the most promising and tantalizing
      future prospects in this area are highlighted.

PMID- 30238144
TI  - [Physical therapy options in rheumatic diseases: what is evidence-based?]
AB  - Rheumatic diseases usually progress towards morphological and functional deficits
      and thus cause impairment of physical health and function. Based on this fact,
      physiotherapeutic options are elementary and indispensable. This article focuses
      on the significance and importance of physiotherapy in inflammatory and
      degenerative rheumatic diseases. Furthermore, an overview is presented on the
      consequences of rheumatic diseases, the reality of supply of physiotherapy, the
      principles and therapeutic options, and the evidence.

PMID- 30238145
TI  - Cervical posterior longitudinal ligament ossification : Microscopy-assisted
      anterior corpectomy and fusion.
AB  - OBJECTIVE: To explore the clinical efficacy and safety of microscopy-assisted
      anterior corpectomy and fusion for cervical ossification of the posterior
      longitudinal ligament (OPLL). METHODS: A retrospective review of 32 cervical OPLL
      patients who underwent microscopy-assisted anterior corpectomy and fusion from
      June 2012 to March 2017 was carried out. Patients were evaluated with outcome
      metrics: Japanese Orthopaedic Association (JOA) scores (17 points method), visual
      analog scale (VAS), and radiographic parameters of the lordotic angle. The
      complications during treatment and follow-up were recorded. RESULTS: This study
      included 32 patients (15 males and 17 females) with a mean age of 58.3 +/- 2.9
      years (range 42-68 years). The average duration of follow-up was 19.0 +/- 3.5
      months (range 11-46 months). The scores of postoperative VAS significantly
      decreased (P < 0.05). The average JOA score at 12 months postoperation
      significantly improved (p < 0.05). The lordotic angle increased after surgery (P
      < 0.05). There was no titanium mesh subsidence, no pseudarthrosis or hardware
      failure at 1-year follow-up. COMPLICATIONS: One cerebrospinal fluid leakage in
      the surgery was managed using a gelatine sponge and the patient recovered after 1
      week: One patient developed laryngeal nerve injury symptom of hoarseness and
      recovered spontaneously in 2 weeks without intervention and 1 patient suffered
      slight postoperative infection. There was no worsening of neurological function.
      CONCLUSION: Microscopy-assisted anterior cervical anterior surgery appears to be
      a safe and effective treatment option for selected cases of cervical posterior
      longitudinal ligament ossification.

PMID- 30238146
TI  - Acute and Chronic Lead Exposure in Four Avian Scavenger Species in Switzerland.
AB  - Despite irrefutable evidence of its negative impact on animal behaviour and
      physiology, lethal and sublethal lead poisoning of wildlife is still persistent
      and widespread. For scavenging birds, ingestion of ammunition, or fragments
      thereof, is the major exposure route. In this study, we examined the occurrence
      of lead in four avian scavengers of Switzerland and how it differs between
      species, regions, and age of the bird. We measured lead concentration in liver
      and bone of the two main alpine avian scavengers (golden eagle Aquila chrysaetos
      and bearded vulture Gypaetus barbatus) over the entire area of the Swiss Alps and
      two of the main avian scavengers occurring in the lowlands of Switzerland (red
      kite Milvus milvus and common raven Corvus corax). Of those four species, only
      the bearded vulture is an obligate scavenger. We found that lead burdens in the
      two alpine avian scavengers were higher than those found for the same species
      elsewhere in Europe or North America and reached levels compatible with acute
      poisoning, whereas lead burdens of the two lowland avian scavengers seemed to be
      lower. Several golden eagles, but only one red kite with abnormally high bone
      lead concentrations were found. In all four species, a substantial proportion of
      birds had elevated levels which presumably represent recent (liver lead levels)
      or past (bone lead levels) uptake of sublethal doses of lead.

PMID- 30238147
TI  - Interactions Between Silver Nanoparticles/Silver Ions and Liposomes: Evaluation
      of the Potential Passive Diffusion of Silver and Effects of Speciation.
AB  - Silver nanoparticles, used mainly for their antibacterial properties, are among
      the most common manufactured nanomaterials. How they interact with aquatic
      organisms, especially how they cross biological membranes, remains uncertain.
      Free Ag+ ions, released from these nanoparticles, are known to play an important
      role in their overall bioavailability. In this project, we have studied the
      uptake of dissolved and nanoparticulate silver by liposomes. These unilamellar
      vesicles, composed of phospholipids, have long been used as models for natural
      biological membranes, notably to study the potential uptake of solutes by passive
      diffusion through the phospholipid bilayer. The liposomes were synthesized using
      extrusion techniques and were exposed over time to dissolved silver under
      different conditions where Ag+, AgS2O3-, or AgCl0 were the dominant species.
      Similar experiments were conducted with the complexes HgCl 2 0 and Cd(DDC) 2 0 ,
      both of which are hydrophobic and known to diffuse passively through biological
      membranes. The uptake kinetics of Ag+, HgCl 2 0 , and Cd(DDC) 2 0 show no
      increase in internalized concentrations over time, unlike AgS2O3- and AgCl0,
      which appear to pass through the phospholipid bilayer. These results are in
      contradiction with our initial hypothesis that lipophilic Hg and Cd complexes
      would be able to cross the membrane, whereas silver would not. Encapsulated
      tritiated water inside the liposomes was shown to rapidly diffuse through the
      lipid bilayer, suggesting a high permeability. We hypothesize that monovalent
      anions or complexes as well as small neutral complexes with a strong dipole can
      diffuse through our model membrane. Finally, liposomes were exposed to 5-nm
      polyvinylpyrrolidone-coated silver nanoparticles over time. No significant uptake
      of nanoparticulate silver was observed. Neither disruption of the membrane nor
      invagination of nanoparticles into the liposomes was observed. This suggests that
      the main risk caused by AgNPs for nonendocytotic biological cells would be the
      elevation of the free silver concentration near the membrane surface due to
      adsorption of AgNPs and subsequent oxidation/dissolution.

PMID- 30238148
TI  - Neurologic adverse events in patients with relapsed/refractory acute
      lymphoblastic leukemia treated with blinatumomab: management and mitigating
      factors.
AB  - Neurologic events (NEs) have been reported during treatment with blinatumomab, a
      bispecific T cell engager (BiTE(r)) construct. We evaluated the occurrence,
      severity, and management of NEs; the relationship between NEs and blinatumomab
      dose; and the potential clinical risk factors in an open-label, single-arm, phase
      2 study (N = 189). Patients had Philadelphia chromosome-negative,
      relapsed/refractory acute lymphoblastic leukemia (ALL) and >= 10% bone marrow
      blasts. The relationship between blinatumomab exposure and NE incidence and
      severity was assessed. Clinical risk factors for NEs were assessed in a post hoc
      multivariate analysis. Overall, 98 patients (52%) experienced NEs: most
      frequently, dizziness, tremor, confusional state, and encephalopathy. NEs
      occurred predominantly during cycle 1 (median onset, 9 days) and were usually
      grades 1 or 2. Grade >= 3 NEs (13-17% incidence), serious NEs (16-19% incidence),
      and recurring NEs were managed with infusion interruptions or dexamethasone
      treatment. The incidence of NEs increased with increasing blinatumomab exposure
      at a given dose, but exposure appeared unrelated to NE severity. NEs were more
      frequent in patients >= 65 years than < 65 years (72 vs 49%). In a multivariate
      analysis, race other than white (hazard ratio [HR], 2.11; P = 0.009), > 2 prior
      salvage therapies (HR, 2.48; P = 0.006), and prior NEs (HR, 1.65; P = 0.020) were
      risk factors for time to first on-study NE. Although the mechanism underlying NEs
      associated with blinatumomab treatment in patients with relapsed/refractory ALL
      remains unclear, NEs tended to occur early during treatment and were often
      resolved by interrupting treatment and with dexamethasone. Additional research is
      warranted to investigate the risk factors for NEs.

PMID- 30238149
TI  - Utilisation of small paediatric donor kidneys for transplantation.
AB  - With the increasing need for kidney transplantation in the paediatric population
      and changing donor demographics, children without a living donor option will
      potentially be offered an adult deceased donor transplant of marginal quality.
      Given the importance of long-term graft survival for paediatric recipients,
      consideration is now being given to kidneys from small paediatric donors (SPDs).
      There exist a lack of consensus and a reluctance amongst some centres in
      transplanting SPDs due to high surgical complication rates, graft loss and
      concerns regarding low nephron mass and long-term function. The aim of this
      review is to examine and present the evidence base regarding the transplantation
      of these organs. The literature in both the paediatric and adult renal transplant
      fields, as well as recent relevant conference proceedings, is reviewed. We
      discuss the surgical techniques, long-term graft function and rates of
      complications following transplantation of SPDs. We compare graft survival of
      SPDs to adult deceased donors and consider the use of small paediatric donors
      after circulatory death (DCD) organs. In conclusion, evidence is presented that
      may refute historically held paradigms regarding the transplantation of SPDs in
      paediatric recipients, thereby potentially allowing significant expansion of the
      donor pool.

PMID- 30238150
TI  - Total body water measurement in childhood.

PMID- 30238151
TI  - Outcome of membranoproliferative glomerulonephritis and C3-glomerulopathy in
      children and adolescents.
AB  - BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is a rare cause of
      glomerulopathy in children. Recently, a new classification based on
      immunohistological features has been established. Infections and anomalies in
      complement-regulating genes, leading to alternative complement pathway
      activation, are suspected to trigger the disease. Nevertheless, little is known
      about optimal treatment and outcome in children with immune-complex-MPGN (IC
      MPGN) and C3-glomerulopathy (C3G). METHODS: The method used is retrospective
      analysis of clinical, histological, and genetic characteristics of 14 pediatric
      patients with MPGN in two medical centers. RESULTS: Mean age of the patients was
      10.6 +/- 4.5 years. Patients were grouped into C3G (n = 6) and IC-MPGN (n = 8).
      One patient showed a likely pathogenic variant in the CFHR5 gene. All 10 patients
      had risk polymorphisms in complement-regulating genes. Most patients were treated
      with ACE inhibition, steroids, and mycophenolate mofetil. Three patients with C3G
      received eculizumab. Median follow-up was 2.3 years. After 1 year of disease,
      three patients (two C3G, one IC-MPGN) reached complete, five patients partial
      (three IC-MPGN, two C3G), and five patients no remission (four IC-MPGN, one C3G).
      One patient progressed to end-stage renal disease (ESRD) 6 years after disease
      onset. CONCLUSIONS: IC-MPGN and C3G are rare disorders in children. Most patients
      have signs of complement activation associated with risk polymorphisms or likely
      pathogenic variants in complement-regulating genes. Steroids and mycophenolate
      mofetil seem to be effective and for some patients, eculizumab might be a
      treatment option. Outcome is heterogeneous and precise differentiation between IC
      MPGN and C3G is still pending.

PMID- 30238152
TI  - Mycelium of Terfezia claveryi as inoculum source to produce desert truffle
      mycorrhizal plants.
AB  - Terfezia claveryi Chatin was the first desert truffle species to be cultivated,
      the mycorrhizal plants being successfully produced by using both desert truffle
      spores and mycelia. However, it is more advisable to use mycelium than spores
      whenever possible and profitable. Given the low yields of mycelia obtained using
      traditional culture methods of this truffle, the medium composition was modified
      in an attempt to determine its nutritional requirements. For this, an assay
      involving response surface methodology was performed using Box-Behnken design to
      find the optimal parameters for the high production of mycelial biomass. The best
      results were obtained with glucose as carbon source, buffering the pH at 5 during
      culture, adding a pool of vitamins, and adjusting the optimal concentrations of
      carbon and nitrogen sources of the MMN medium. Biomass production increased from
      0.3 to 3 g L-1 dry weight and productivity increased from 10.7 to 95.8 mg L-1 day
      1 dry weight. The produced mycelium was able to colonize Helianthemum roots
      efficiently, providing more than 50% ectomycorrhizal colonization.

PMID- 30238153
TI  - Mealtime insulin bolus adherence and glycemic control in adolescents on insulin
      pump therapy.
AB  - Poor self-management contributes to insufficient glycemic control in adolescents
      with type 1 diabetes (T1DM). We assessed the effects on glycemic control of
      adherence to self-measurement of blood glucose (SMBG) and insulin boluses in 90
      adolescents with T1DM on insulin pump therapy over a 2-month period. We compared
      the number of insulin boluses and SMBGs around main meals to the "gold standard"
      of optimal diabetes management (SMBGs and a bolus before each main meal and SMBG
      before bedtime). The mean (95% CI) HbA1c levels were 2.9(1.7 to 4.0) mmol/mol
      lower for every additional insulin bolus and 3.1(1.6 to 4.5) mmol/mol lower for
      every additional SMBG. Patients performing SMBG and bolusing around each main
      meal had considerably lower HbA1c levels than those unable to do (95% CI for
      difference 4.3 to 10.4 mmol/mol and 11.5 to 20.1 mmol/mol respectively). For each
      additional mealtime bolus/day, the odds ratio of achieving target HbA1c levels of
      <58 mmol/mol was 6.73 (95% CI 2.94-15.38), after adjustment for gender, age,
      diabetes duration, and affective responses to SMBG in a multiple logistic
      regression model.Conclusion: Glycemic control in adolescents with T1DM on insulin
      pump therapy is strongly dependent on adherence to insulin boluses around
      mealtimes. What is Known: * In mixed groups of children and adolescents, insulin
      bolus frequency and self-monitoring of blood glucose (SMBG) frequency were
      determinants of HbA1c levels. * Adherence to insulin boluses and SMBG is
      particularly challenging in adolescents. What is New: * In adolescents on insulin
      pump therapy, each additional insulin bolus, particularly around mealtime, was
      significantly associated with approximately 3 mmol/mol lower HbA1c levels. * This
      beneficial effect of mealtime bolusing was strongest for the evening meal.

PMID- 30238157
TI  - Tumor localization using radio-frequency identification clip marker: experimental
      results of an ex vivo porcine model.
AB  - PURPOSE: With the widespread use of minimally invasive surgery, tumor detection
      is becoming more difficult. We present the experimental results of a radio
      frequency identification (RFID) lesion detection system in an ex vivo porcine
      model. METHODS: The efficacy and feasibility of a newly developed RFID lesion
      detection system were examined. It was applied to the stomach and colon of pigs
      weighing 40 kg. The RFID clip was attached to the upper and lower mucosal sides
      of the stomach. Colon specimens with thin and thick walls were used. The clipped
      sites were marked on the serosa by a pin. The longest distance from the pin the
      RFID tag could be detected was measured 25 times in each direction. RESULTS: In
      the upper gastric wall, the RFID tag detection distance was 4.5 +/- 0.9 mm, 5.6
      +/- 0.7 mm, 12.5 +/- 0.7 mm, and 5.3 +/- 0.5 mm in the four directions,
      respectively (right, left, upper, and lower). In the antrum, the RFID tag
      detection distance was 5.8 +/- 0.7 mm, 6.9 +/- 0.5 mm, 5.6 +/- 0.5 mm, and 3.7 +/
      0.5 mm in the four directions. In the thin colon, the RFID tag detection
      distance was 6.3 +/- 0.5 mm, 5.0 +/- 0.5 mm, 9.7 +/- 0.7 mm, and 6.4 +/- 0.4 mm
      in the four directions. In the thick colon, the RFID tag detection distance was
      3.5 +/- 0.8 mm, 6.6 +/- 0.5 mm, 8.4 +/- 0.6 mm, and 9.8 +/- 0.5 mm in the four
      directions. The area of detection was smallest for the antrum (83.7 mm2) and
      similar for the other sites (150.6, 154.7 and 157.7 mm2 for the upper body, thin
      colon, and thick colon, respectively). CONCLUSIONS: The distance at which the
      RFID tag was detected was usually within 10 mm. These results indicate the
      feasibility of the clinical application of the add-on clip and RFID tag as a
      marker for identifying the location of various gastrointestinal tumors.

PMID- 30238156
TI  - Changes in electrophysiological properties of photoreceptors in Periplaneta
      americana associated with the loss of screening pigment.
AB  - Absence of screening pigment in insect compound eyes has been linked to visual
      dysfunction. We investigated how its loss in a white-eyed mutant (W-E) alters the
      photoreceptor electrophysiological properties, opsin gene expression, and the
      behavior of the cockroach, Periplaneta americana. Whole-cell patch-clamp
      recordings of green-sensitive photoreceptors in W-E cockroaches gave reduced
      membrane capacitance, absolute sensitivity to light, and light-induced currents.
      Decreased low-pass filtering increased voltage-bump amplitudes in W-E
      photoreceptors. Intracellular recordings showed that angular sensitivity of W-E
      photoreceptors had two distinct components: a large narrow component with the
      same acceptance angle as wild type, plus a relatively small wide component.
      Information processing was evaluated using Gaussian white-noise modulated light
      stimulation. In bright light, W-E photoreceptors demonstrated higher signal gain
      and signal power than wild-type photoreceptors. Expression levels of the primary
      UV- and green-sensitive opsins were lower and the secondary green-sensitive opsin
      significantly higher in W-E than in wild-type retinae. In behavioral experiments,
      W-E cockroaches were significantly less active in dim green light, consistent
      with the relatively low light sensitivity of their photoreceptors. Overall, these
      differences can be related to the loss of screening pigment function and to a
      compensatory decrease in the rhabdomere size in W-E retinae.

PMID- 30238155
TI  - Pexophagy in yeast and mammals: an update on mysteries.
AB  - Peroxisomes are ubiquitous and highly dynamic organelles that play a central role
      in the metabolism of lipids and reactive oxygen species. The importance of
      peroxisomal metabolism is illustrated by severe peroxisome biogenesis disorders
      in which functional peroxisomes are absent or disorders caused by single
      peroxisomal enzyme deficiencies. These multisystemic diseases manifest specific
      clinical and biochemical disturbances that originate from the affected
      peroxisomal pathways. An emerging role of the peroxisome has been identified in
      many types of diseases, including cancer, neurodegenerative disorders, aging,
      obesity, and diabetes. Peroxisome homeostasis is achieved via a tightly regulated
      interplay between peroxisome biogenesis and degradation via selective autophagy,
      which is commonly known as "pexophagy". Dysregulation of either peroxisome
      biogenesis or pexophagy may be detrimental to the health of cells and contribute
      to the pathophysiology of these diseases. Autophagy is an evolutionary conserved
      catabolic process for non-selective degradation of macromolecules and organelles
      in response to various stressors. In selective autophagy, specific cargo
      recognizing receptors connect the cargo to the core autophagic machinery, and
      additional posttranslational modifications such as ubiquitination and
      phosphorylation regulate this process. Several stress conditions have been shown
      to stimulate pexophagy and decrease peroxisome abundance. However, our
      understanding of the mechanisms that particularly regulate mammalian pexophagy
      has been limited. In recent years considerable progress has been made uncovering
      signaling pathways, autophagy receptors and adaptors as well as posttranslational
      modifications involved in pexophagy. In this review, which is published back-to
      back with a peroxisome review by Islinger et al. [(Histochem Cell Biol 137:547
      574, 2018). The peroxisome: an update on mysteries 2.0], we focus on recent novel
      findings on the underlying molecular mechanisms of pexophagy in yeast and
      mammalian cells and highlight concerns and gaps in our knowledge.

PMID- 30238159
TI  - Correction to: Gender differences in SCRABBLE performance and associated
      engagement in purposeful practice activities.
AB  - Correcting Table 5. SEM results for four factors without the variables of age,
      starting age, and first tournament age. Statistically significant paths and
      values are black, and non-significant paths and values are gray.

PMID- 30238158
TI  - Three-port totally endoscopic repair vs conventional median sternotomy for atrial
      septal defect.
AB  - PURPOSES: We assessed the validity of three-port totally endoscopic repair
      (3PTER) for atrial septal defect (ASD). METHODS: Between February, 2000 and
      November, 2017, 151 patients underwent surgery for ASD. Forty-seven patients
      underwent 3PTER as minimally invasive cardiac surgery (MICS) and 104 patients
      underwent conventional median sternotomy (CMS). Propensity matching yielded 94
      matched patients (47 vs 47). We compared the early results between the groups.
      The 3PTER technique was performed with the patient in the partial left lateral
      position, under cardio-pulmonary bypass (CPB) established through a groin
      incision. The three ports consisted of a main incision (3 cm), a trocar for the
      left-handed instrument, and a camera port in right antero-lateral chest. RESULTS:
      MICS needed longer cross clamp and CPB times (57, 48-86 vs 24, 16-30 min, p <
      0.01 and 115, 106-131 vs 53, 43-80 min, p < 0.01, respectively)*, although the
      operation time and hospital stay were significantly shorter (180, 159-203 vs 190,
      161-225 min, p = 0.024 and 6.0, 6-8 vs 15, 13-19 days, p < 0.01, respectively)*.
      The intra-operative and postoperative bleeding were significantly less in MICS
      than CMS (20, 5-40 vs 225, 130-287.5 p < 0.01 and 200, 145-290 vs 340, 250-535
      ml, p < 0.01, respectively)*. *: median, 25th-75th percentile. CONCLUSION:
      Irrespective of the longer CPB and cross-clamp time than for CMS, MICS had a
      shorter operation time, less bleeding, and resulted in quicker recovery. The
      3PTER was safe and cosmetically excellent.

PMID- 30238154
TI  - Blank spots on the map: some current questions on nuclear organization and genome
      architecture.
AB  - The past decades have provided remarkable insights into how the eukaryotic cell
      nucleus and the genome within it are organized. The combined use of imaging,
      biochemistry and molecular biology approaches has revealed several basic
      principles of nuclear architecture and function, including the existence of
      chromatin domains of various sizes, the presence of a large number of non
      membranous intranuclear bodies, non-random positioning of genes and chromosomes
      in 3D space, and a prominent role of the nuclear lamina in organizing genomes.
      Despite this tremendous progress in elucidating the biological properties of the
      cell nucleus, many questions remain. Here, we highlight some of the key open
      areas of investigation in the field of nuclear organization and genome
      architecture with a particular focus on the mechanisms and principles of higher
      order genome organization, the emerging role of liquid phase separation in
      cellular organization, and the functional role of the nuclear lamina in
      physiological processes.

PMID- 30238160
TI  - Postmortem interrogation of cardiac implantable electrical devices may clarify
      time and cause of death.
AB  - BACKGROUND: Postmortem interrogation of cardiac implantable electrical devices
      (CIED) in autopsy is not routinely performed. Thus, it remains unclear whether an
      interrogation might clarify time and cause of death. METHODS: Seventy of 4401
      patients (1.6%) undergoing autopsy in 2014 and 2015 presented with a CIED. The
      explanted CIED were interrogated with respect to time and possible cause of
      death. Battery and lead parameters, clinical and technical alerts, and arrhythmia
      episodes were reviewed and afterwards correlated with the results of autopsy and
      clinical data. RESULTS: Twenty-five implantable cardioverter defibrillators (ICD)
      and 45 pacemaker (PM) devices were analyzed. Death was classified as cardiac by
      autopsy in 17 of 70 patients. Accordingly, presumably lethal ventricular
      arrhythmias were documented in six patients (8.6%; 5 ICD, 1 PM). In two of 30
      patients with unknown cause of death after autopsy (6.7%), interrogation revealed
      ventricular tachycardia as potential reason for decease (1 ICD, 1 PM). Postmortem
      CIED interrogation additionally allowed to make a statement regarding the day of
      death in 36 patients (51%; 13 ICD, 23 PM). This was in accordance with clinical
      data or the results of autopsy in nine patients (25%; 3 ICD, 6 PM) or could even
      clarify the time of death in six patients (16.7%; 4 ICD, 2 PM). CONCLUSION:
      Interrogation of CIED revealed potentially lethal ventricular arrhythmias in 9 of
      70 patients investigated and enabled valid estimation of the day of death in 15
      patients. We therefore conclude that routinely performed postmortem CIED
      interrogation may clarify time and cause of death.

PMID- 30238161
TI  - Predatory behavior of Synthesiomyia nudiseta larvae (Diptera: Muscidae) on
      several necrophagous blowfly species (Diptera: Calliphoridae).
AB  - Intraguild interactions play a prominent role in sarcosaprophagous communities,
      so intraspecific and interspecific competition phenomena between fly larvae take
      place. Synthesiomyia nudiseta is a species that has recently been recorded on
      human corpses in Europe, and it has been cited in forensic cases in Spain and
      Italy. The mature larvae are known to be facultative predators on necrophagous
      fly larvae, but their role as predators is unknown. The aim of this paper is to
      investigate the predatory behavior of S. nudiseta on the most abundant blowfly
      larvae in sarcosaprophagous communities in southwestern Europe (i.e., Chrysomya
      albiceps, Lucilia sericata, and Calliphora vicina). Intraspecific and
      interspecific competition experiments were carried out to study the effect of
      this species in the necrophagous diptera community. First-instar larvae were
      placed in plastic cups with the same amount of pig liver (15 g) at different
      densities (50, 100, 150, and 300 individuals/cup). Mortality in blowflies
      increased when S. nudiseta larvae were present: up to 98.40% in Ch. albiceps,
      89.60% in L. sericata, and 84.93% in C. vicina. Pre-imaginal developmental time
      and adult wing size were analyzed and compared under each of the intraspecific
      and interspecific conditions; both variables were affected by competition in all
      cases. The implications of the presence of S. nudiseta for sarcosaprophagous
      community dynamics and its effect on the estimation of postmortem interval (PMI)
      are discussed.

PMID- 30238162
TI  - Complete genome sequence of C130_2, a novel myovirus infecting pathogenic
      Escherichia coli and Shigella strains.
AB  - The genome sequence of a novel virulent bacteriophage, named " C130_2", that is
      morphologically a member of the family Myoviridae is reported. The 41,775-base
      pair double-stranded DNA genome of C130_2 contains 59 ORFs but exhibits overall
      low sequence similarity to bacteriophage genomes for which sequences are publicly
      available. Phylogenetic analysis indicated that C130_2 represents a new phage
      type. C130_2 could be propagated well on enterohemorrhagic Escherichia coli
      (EHEC) O157:H7 and other pathogenic E. coli strains, as well as on strains of
      various Shigella species.

PMID- 30238163
TI  - Characterization of mule deerpox virus in Florida white-tailed deer fawns expands
      the known host and geographic range of this emerging pathogen.
AB  - Infections caused by mule deerpox virus (MDPV) have been sporadically reported in
      North American cervids. White-tailed deer (Odocoileus virginianus) fawns from a
      farm located in South Central Florida presented with ulcerative and crusting
      lesions on the coronary band as well as the mucocutaneous tissues of the head.
      Evaluation of the crusted skin lesions was undertaken using microscopic pathology
      and molecular techniques. A crusted skin sample was processed for virus isolation
      in four mammalian cell lines. The resulting isolate was characterized by negative
      staining electron microscopy and deep sequencing. Histopathologic evaluation of
      the skin lesions from the fawns revealed a hyperplastic and proliferative
      epidermis with ballooning degeneration of epidermal and follicular keratinocytes
      with intracytoplasmic eosinophilic inclusions. Electron microscopy of cell
      culture supernatant demonstrated numerous large brick-shaped particles typical of
      most poxviruses. Polymerase chain reaction assays followed by Sanger sequencing
      revealed a poxvirus gene sequence nearly identical to that of previous strains of
      MDPV. The full genome was recovered by deep sequencing and genetic analyses
      supported the Florida white-tailed deer isolate (MDPV-F) as a strain of MDPV.
      Herein, we report the first genome sequence of MDPV from a farmed white-tailed
      deer fawn in the South Central Florida, expanding the number of locations and
      geographic range in which MDPV has been identified.

PMID- 30238165
TI  - Traffic Priority Based Channel Assignment Technique for Critical Data
      Transmission in Wireless Body Area Network.
AB  - In recent days, intelligent biomedical sensors and wearable devices are changing
      the healthcare industry by providing various heterogeneous vital signs of
      patients to the hospitals, caregivers, and clinicals. This collective form of
      monitoring sensor devices forms a very short-range Wireless Body Area Network
      (WBAN) and plays a key role in the data gathering process. If any sensor node in
      the network detects abnormal values that should be transmitted promptly via
      wireless medium with less delay. A single medium allows one-way delivery of a
      data packet, and it may not be sufficient to satisfy the high volume of
      communication demand between the sensor nodes in the network. In the same way,
      the packet prioritization does not guarantee the packet will get there on time
      and sometime it may cause priority conflicts among the nodes. It is only mean
      that the flow of delivery service handles that critical data packet before
      handling other data packets. However, unexploited time slots and bandwidth
      wastage will occur due to inefficient backoff management and collisions. To
      minimize the aforementioned issues, various backoff procedures, adaptive slot
      allocation mechanisms, priority-based medium access control protocols have been
      developed but suffer limitations in the context of providing priority-based
      channel access with less backoff conflicts and dedicated allocation of time slots
      for critical nodes in all cases. Based on these deliberations, a more effective
      Traffic Priority-based Channel Access Technique (TP-CAT) is proposed using IEEE
      802.15.6 in order to minimize the transmission delay of critical data packet and
      solve conflicts among other priority nodes during the backoff phases. Firstly, a
      Low Threshold Criticality-based Adaptive Time slot Allocation algorithm (LT-CATA)
      is presented to decrease the priority slot conflicts between the low threshold
      data traffic from the same and different type of user priority nodes. Secondly, a
      High Threshold Criticality-based Adaptive Time slot Allocation algorithm (HT
      CATA) is developed to reduce the priority slot conflicts between the high
      threshold data traffic from the same and different types of user priority nodes.
      Additionally, a novel Random Overlapping Backoff value Avoidance (ROBA) technique
      is introduced to eliminate the overlapping issue during the selection of random
      backoff value among the sensor nodes. Since, the proposed technique greatly
      reduced the channel access delay and transmission delay of critical data packet
      as well as other types of priority data packet. The Simulation results are
      verified in the CASTALIA 3.2 framework using omnet++ network simulater to
      relatively evaluate the performance metrics of the TP-CAT technique with state-of
      the-art protocols. From the analysis of the results, it is evident that the TP
      CAT technique provides better performance in terms of delay, energy consumption,
      and throughput in healthcare monitoring environments.

PMID- 30238164
TI  - Performance analysis of automated evaluation of antinuclear antibody indirect
      immunofluorescent tests in a routine setting.
AB  - PURPOSE: Indirect immunofluorescence (IIF) on the human epithelial cell-line HEp
      2 (or derivatives) serves as the gold standard in antinuclear antibody (ANA)
      screening. IIF, and its evaluation, is a labor-intensive method, making ANA
      testing a major challenge for present clinical laboratories. Nowadays, several
      automated ANA pattern recognition systems are on the market. In the current
      study, the EUROPattern Suite is evaluated for its use in daily practice in a
      routine setting. METHODS: A total of 1033 consecutive routine samples was used to
      screen for ANA. Results (positive/negative ANA screening, pattern identification
      and titer) were compared between software-generated results (EUROPattern) and
      visual interpretation (observer) of automatically acquired digital images.
      RESULTS: Considering the visual interpretation as reference, a relative
      sensitivity of 99.3% and a relative specificity of 88.9% were obtained for
      negative and positive discrimination by the software (EPa). A good agreement
      between visual and software-based interpretation was observed with respect to
      pattern recognition (mean kappa: for 7 patterns: 0.7). Interestingly, EPa
      software distinguished more patterns per positive sample than the observer (on
      average 1.5 and 1.2, respectively). Finally, a concordance of 99.3% was observed
      within the range of 1 titer step difference between EPa and observer.
      CONCLUSIONS: The ANA IIF results reported by the EPa software are in very good
      agreement with the results reported by the observer with respect to being
      negative/positive, pattern recognition and titer, making automated ANA IIF
      evaluation an objective and time-efficient tool for routine testing.

PMID- 30238166
TI  - Autism Spectrum Disorder and Transition-Aged Youth.
AB  - PURPOSE OF REVIEW: This article discusses common issues surrounding transition to
      adulthood in youth with autism spectrum disorder (ASD). We review recent evidence
      on co-occurring medical and mental health conditions and topics of education and
      employment, sexuality and relationships, independent living, and financial
      support. RECENT FINDINGS: Transitioning individuals with ASD have increased risk
      for several medical and behavioral health comorbidities and should be routinely
      screened for co-occurring conditions. Evidence on interventions for mental health
      disorders is limited but emerging, particularly with respect to mindfulness
      training and cognitive behavioral therapy. Many autistic adults or their families
      express a desire for independent living, participation in education/employment,
      and intimacy and social relationships, but they often lack skills and/or
      resources to successfully achieve these outcomes. The time of transition to
      adulthood for adolescents with ASD is an opportunity for physicians to provide
      anticipatory guidance and necessary supports around issues of community
      participation. To allow time for planning, these discussions should occur well
      before the child reaches adulthood. Clinicians should also routinely screen for
      and address medical and/or behavioral health comorbidities.

PMID- 30238167
TI  - Dermatoscopy of Neoplastic Skin Lesions: Recent Advances, Updates, and Revisions.
AB  - OPINION STATEMENT: Dermatoscopy (dermoscopy) improves the diagnosis of benign and
      malignant cutaneous neoplasms in comparison with examination with the unaided eye
      and should be used routinely for all pigmented and non-pigmented cutaneous
      neoplasms. It is especially useful for the early stage of melanoma when melanoma
      specific criteria are invisible to the unaided eye. Preselection by the unaided
      eye is therefore not recommended. The increased availability of polarized
      dermatoscopes, and the extended use of dermatoscopy in non-pigmented lesions led
      to the discovery of new criteria, and we recommend that lesions should be
      examined with polarized and non-polarized dermatoscopy. The "chaos and clues
      algorithm" is a good starting point for beginners because it is easy to use,
      accurate, and it works for all types of pigmented lesions not only for those
      melanocytic. Physicians, who use dermatoscopy routinely, should be aware of new
      clues for acral melanomas, nail matrix melanomas, melanoma in situ, and nodular
      melanoma. Dermatoscopy should also be used to distinguish between different
      subtypes of basal cell carcinoma and to discriminate highly from poorly
      differentiated squamous cell carcinomas to optimize therapy and management of non
      melanoma skin cancer. One of the most exciting areas of research is the use of
      dermatoscopic images for machine learning and automated diagnosis. Convolutional
      neural networks trained with dermatoscopic images are able to diagnose pigmented
      lesions with the same accuracy as human experts. We humans should not be afraid
      of this new and exciting development because it will most likely lead to a
      peaceful and fruitful coexistence of human experts and decision support systems.

PMID- 30238170
TI  - Sudden unexpected death in Parkinson's disease: why do neuroscientists still
      ignore this condition?

PMID- 30238169
TI  - Predicting sanitary landfill leachate generation in humid regions using ANFIS
      modeling.
AB  - Landfill leachate is one of the sources of surface water pollution in Selangor
      State (SS), Malaysia. Leachate volume prediction is essential for sustainable
      waste management and leachate treatment processes. The accurate estimation of
      leachate generation rates is often considered a challenge, especially in
      developing countries, due to the lack of reliable data and high measurement
      costs. Leachate generation is related to several variable factors, including
      meteorological data, waste generation rates, and landfill design conditions.
      Large variations in these factors lead to complicated leachate modeling
      processes. The aims of this study are to determine the key elements contributing
      to leachate production and then develop an adaptive neural fuzzy inference system
      (ANFIS) model to predict leachate generation rates. Accuracy of the final model
      performance was tested and evaluated using the root mean square error (RMSE), the
      mean absolute error (MAE), and the correlation coefficient (R). The study results
      defined dumped waste quantity, rainfall level, and emanated gases as the most
      significant contributing factors in leachate generation. The best model structure
      consisted of two triangular fuzzy membership functions and a hybrid training
      algorithm with eight fuzzy rules. The proposed ANFIS model showed a good
      performance with an overall correlation coefficient of 0.952.

PMID- 30238168
TI  - Nanotechnology in Tuberculosis: State of the Art and the Challenges Ahead.
AB  - Tuberculosis (TB) remains as the second most-deadly infection right behind the
      HIV/AIDS. Actually, in 2016, TB incidence was estimated in 10.4 million cases.
      Although an efficient and low-cost TB pharmacotherapy has been available for the
      last 50 years, the development of multi- and extra-drug-resistant Mycobacterium
      tuberculosis (Mtb) strains has put on the spot the necessity of improved TB
      regimens. In this framework, this review article presents the main relevant
      research outcomes of nanotechnology in TB. The novel delivery systems for
      antituberculosis drugs have been discussed. Moreover, the active-targeted
      nanomedicines to the Mtb reservoirs enlighten the possibility to eradicate low
      replicant mycobacteria and diminish latent TB. Finally, we present an overview of
      the TB socio-economic impact and the cost-related features of TB regimens
      associated with the use of nanoformulations.

PMID- 30238171
TI  - Impact of upfront randomization for postoperative treatment on quality of surgery
      in the CRITICS gastric cancer trial.
AB  - BACKGROUND: Preoperative randomization for postoperative treatment might affect
      quality of surgery. In the CRITICS trial (ChemoRadiotherapy after Induction
      chemotherapy In Cancer of the Stomach), patients were randomized before treatment
      to receive chemotherapy prior to a D1 + gastrectomy (removal of lymph node
      station (LNS) 1-9 + 11), followed by either chemotherapy (CT) or
      chemoradiotherapy (CRT). In this analysis, the influence of upfront randomization
      on the quality of surgery was evaluated. METHODS: Quality of surgery was analyzed
      in both study arms using surgicopathological compliance (removal of >= 15 lymph
      nodes), surgical compliance (removal of the indicated LNS), and surgical
      contamination (removal of LNS that should be left in situ). Furthermore, the
      'Maruyama Index of Unresected disease' (MI) was evaluated in both study arms, and
      validated with overall survival. RESULTS: Between 2007 and 2015, 788 patients
      with gastric cancer were included in the CRITICS study of which 636 patients were
      operated with curative intent. No difference was observed between the CT and CRT
      group regarding surgicopathological compliance (74.8% vs 70.9%, P = 0.324),
      surgical compliance (43.2% vs 39.2%, P = 0.381), and surgical contamination
      (59.4% vs 59.9%, P = 0.567). Median MI was 1 in both groups (range CT 0-88 and
      CRT 0-136, P = 0.700). A MI below 5 was associated with better overall survival
      (CT: P = 0.009 and CRT: P = 0.013). CONCLUSION: Surgical quality parameters were
      similar in both study arms in the CRITICS gastric cancer trial, indicating that
      upfront randomization for postoperative treatment had no impact on the quality of
      surgery. A Maruyama Index below five was associated with better overall survival.

PMID- 30238172
TI  - Computed tomography for suspected pulmonary embolism results in a large number of
      non-significant incidental findings and follow-up investigations.
AB  - INTRODUCTION: Computed tomographic pulmonary angiograms (CTPAs) are often ordered
      to evaluate pulmonary embolism (PE) in the emergency department (ED). The
      increase use of CTPA has led to an increase in incidental findings, often of low
      clinical significance. Our objectives were to (1) assess the prevalence and
      clinical significance of incidental findings identified in patients evaluated
      with CTPAs for PE in the ED, (2) evaluate follow-up investigations for these
      incidental findings, and (3) assess the utility of routine chest X-rays done
      prior to CTPA. METHODS: This is a historical cohort study of adult patients,
      presenting to two tertiary care EDs from January-December 2015, evaluated with
      CTPA for possible PE. Two reviewers' extracted data from electronic CT records in
      a standardized fashion with inter-rater reliability reported using the kappa
      statistic. We measured the prevalence of PE and stratified non-PE findings
      according to alternative diagnoses and incidental findings. Data were reported as
      mean and standard deviation (SD). Univariate analyses were performed with t test
      for continuous variables. RESULTS: A total of 1708 studies were included (mean 62
      years (SD 16.7), 56.9% female). PE was found in 233 (13.6%) patients. A total of
      223 (13.1%) patients had an incidental finding, the majority of which included
      pulmonary nodules (n = 83, 37.2%) and adenopathy (n = 26, 11.6%). Of the
      incidental findings, 197 (88.3%) were non-significant and led to no definitive
      diagnosis of cancer. In patients who underwent both CTPA and chest X-ray, X-ray
      reports revealed the same diagnosis in 77% of PE-negative patients without
      missing a clinically significant incidental finding. CONCLUSIONS: Incidental
      findings are as common as a diagnosis of PE in patients undergoing CTPA. They are
      rarely clinically significant. Chest radiograph remains a reasonable initial
      investigation as it can aid in identifying alternative diagnoses especially in
      the setting of a low pre-test probability for PE.

PMID- 30238173
TI  - 12th European Headache Federation Congress jointly with 32nd National Congress of
      the Italian Society for the Study of Headaches : Florence, Italy. 28-30 September
      2018.

PMID- 30238175
TI  - Molecular identification of some wild Nigerian mushrooms using internal
      transcribed spacer: polymerase chain reaction.
AB  - Identification of fungal species based on morphological characteristics is
      tedious, complex, prone to errors, and thus cannot be completely relied upon. In
      this study, internal transcribed spacers (ITS 1 and 4)-polymerase chain reaction
      was employed to amplify DNA of 19 mushroom isolates collected at Environmental
      Pollution Science and Technology farm, Ilesa, Southwest Nigeria. The PCR
      amplification of ITS1 and 4 of the mushrooms isolates yielded approximately 850
      bp. Amplicons obtained were sequenced and identified using BLASTn in the NCBI.
      The BLASTn results revealed that Termitomyces aurantiacus (3), Tricholoma
      matsutake (8), Tricholoma robustum (2), P. ostreatus (4), Schizophyllum commune
      (1) and Pleurotus pulmonarius (1) were fully represented. Only Tricholoma
      matsutake (KT273371), Pleurotus pulmonarius (KY962469) and Tricholoma matsutake
      (AF438605) had 100% similarity with reference strain. However, the phylogenetic
      analysis of the isolates showed low genetic relatedness with reference strains.
      This study revealed the novelty of the mushroom strains and thus advocating the
      need for strict conservation measures and further investigations on their
      potential benefits to mankind.

PMID- 30238176
TI  - In vitro maturation (IVM) of oocytes in patients with resistant ovary syndrome
      and in patients with repeated deficient oocyte maturation.
AB  - PURPOSE: To assess the efficiency of IVM in patients with repeated ART failure
      due to resistant ovary syndrome or due to deficient oocyte maturation. METHODS:
      Clinical and laboratory data were obtained retrospectively from 28 patients who
      underwent 49 cycles of IVM between 2010 and 2017; nine patients had resistant
      ovary syndrome and 19 patients had repeated deficient oocyte maturation. RESULTS:
      Nine patients with resistant ovary syndrome underwent 24 IVM cycles. In those, an
      average of 11.5 +/- 10.4 cumulus-oocyte complexes (COC) was retrieved, and IVM
      resulted in 3.4 +/- 3.1 mature oocytes. After ICSI and transfer of 23 cleavage
      stage embryos, eight pregnancies were obtained, resulting in five healthy live
      births. The live birth rate was 16.7% per started cycle and 33.3% per patient.
      Nineteen patients with a history of deficient oocyte maturation underwent 25 IVM
      cycles. An average of 10.6 +/- 9.2 COC was retrieved, and after IVM, 1.3 +/- 2.1
      oocytes were mature. No mature oocytes were obtained in 11 cycles. In ten cycles
      with mature oocytes, none of them fertilized after ICSI. Out of four cycles with
      fertilized oocytes, only one good-quality embryo was obtained. No live births
      were obtained after IVM in patients with a history of deficient oocyte
      maturation. CONCLUSIONS: Based on our experience, IVM is a valuable approach in
      patients with resistant ovary syndrome, but should not be recommended for
      patients with deficient oocyte maturation.

PMID- 30238178
TI  - Genetic counselling of young women with breast cancer for Li-Fraumeni syndrome: a
      nationwide survey on the experiences and attitudes of genetics professionals.
AB  - Germline TP53 mutations are associated with an increased risk of early-onset
      breast cancer. Traditionally, it was not standard practice to offer TP53 genetic
      testing due to the low mutation detection rate and limited options regarding
      preventive screening. Recent guidelines recommend that all women diagnosed with
      breast cancer before the age of 31, irrespective of family history, should be
      offered TP53 genetic testing. This study aims to gain more knowledge on the
      attitudes and experiences among genetics professionals regarding the timing and
      content of genetic counselling of young breast cancer patients for Li-Fraumeni
      syndrome (LFS). We conducted a nationwide online survey among genetics
      professionals who provide cancer genetic counselling in the Netherlands. Fifty
      seven professionals completed the questionnaire (response rate overall 54%,
      clinical geneticists 70%). Most respondents reported that they discuss the option
      of TP53 genetic testing-simultaneously with BRCA 1/2-during the initial
      counselling visit, especially in case of referral for treatment-focused genetic
      counselling. There was a general consensus about ten information items that
      should be discussed during counselling. Sixty-one percent of genetics
      professionals did not encounter difficulties in providing genetic counselling for
      LFS, but a substantial minority (29%) did. This study offers valuable insight,
      which will be useful for clinical practice. Studies which address young breast
      cancer patients' attitudes and preferences regarding the timing and content of
      counselling are warranted to further determine the most appropriate genetic
      counselling strategy for these women.

PMID- 30238174
TI  - Renal failure in critically ill patients, beware of applying (central venous)
      pressure on the kidney.
AB  - The central venous pressure (CVP) is traditionally used as a surrogate of
      intravascular volume. CVP measurements therefore are often applied at the bedside
      to guide fluid administration in postoperative and critically ill patients.
      Pursuing high CVP levels has recently been challenged. A high CVP might impede
      venous return to the heart and disturb microcirculatory blood flow which may
      cause tissue congestion and organ failure. By imposing an increased "afterload"
      on the kidney, an elevated CVP will particularly harm kidney hemodynamics and
      promote acute kidney injury (AKI) even in the absence of volume overload.
      Maintaining the lowest possible CVP should become routine to prevent and treat
      AKI, especially when associated with septic shock, cardiac surgery, mechanical
      ventilation, and intra-abdominal hypertension.

PMID- 30238179
TI  - Correction to: Brief Report: Maternal Opioid Prescription from Preconception
      Through Pregnancy and the Odds of Autism Spectrum Disorder and Autism Features in
      Children.
AB  - The original version of this article unfortunately contained a mistake in Table
      2. The "Time of use" should be the column header with the corresponding row with
      "N = 126" belonging to the "Peri-pregnancy" row. The "Preconception" row should
      be the row with "N = 17", "Trimester 1" should be the "N = 29" row, "Trimester 2"
      should be the "N = 25" row, and "Trimester 3" should be the "N = 47" row.

PMID- 30238177
TI  - Dickkopf-1 (Dkk1) protein expression in breast cancer with special reference to
      bone metastases.
AB  - Dysregulation of the Wnt inhibitor dickkopf-1 protein (Dkk1) has been reported in
      a variety of cancers. In addition, it has been linked to the progression of
      malignant bone disease by impairing osteoblast activity. This study investigated
      serum- and tissue levels of Dkk1 in breast cancer patients with- or without bone
      metastases. Serum Dkk1 levels were measured by ELISA in 89 breast cancer patients
      and 86 healthy women. Tissue levels of Dkk1 and beta-catenin, a major downstream
      component of Wnt transduction pathway, were tested with immunohistochemical
      staining in 143 different tissues, including adjacent non-tumoral breast tissues,
      primary breast tumours, lymph nodes metastases, and bone metastases. Serum levels
      of Dkk1 were significantly increased in breast cancer patients without metastases
      compared with healthy controls and even more increased in patients with bone
      metastases. Tissue expression of Dkk1 was positive in 70% of tested primary
      breast cancer tissues and demonstrated significant correlation with histological
      type and PR status. Less frequent expression of Dkk1 was found in lymph nodes
      metastases and bone metastases compared with adjacent non-tumoral breast tissues
      and primary breast tumours. Tissue expression of beta-catenin was positive in the
      vast majority of all tested tissue types indicating activated Wnt/beta-catenin
      signalling. Our results suggested that Wnt/beta-catenin signalling in breast
      tumours and their secondary lymph nodes- and bone metastases is dysregulated and
      this could be related to aberrant Dkk1 expression levels. Hence, Dkk1 protein
      might provide insights into the continued development of novel comprehensive and
      therapeutic strategies for breast cancer and its bone metastases.

PMID- 30238180
TI  - Sensitivity and Specificity of the ADOS-2 Algorithm in a Large German Sample.
AB  - The aim of the present study was to establish diagnostic validity of the new
      algorithm of the Autism Diagnostic Observation Scale, the ADOS-2, to
      differentiate between ASD and other clinically relevant psychiatric and
      developmental disorders in a large German sample. Validity of ADOS and ADOS-2
      diagnostic algorithms was established in 826 individuals (n = 455 autism, n = 216
      autism spectrum, n = 155 non-ASD patients) by receiver operating curves.
      Confidence intervals overlapped largely for ADOS and ADOS-2 algorithms,
      confirming diagnostic validity of both algorithms. Adding information of the
      Social Communication Questionnaire and the Social Responsiveness Scale resulted
      in slightly improved classification rates for autism in Module 4. We thus
      replicated previous findings of the diagnostic validity of the ADOS-2 algorithms.

PMID- 30238181
TI  - Should physicians be empathetic? Rethinking clinical empathy.
AB  - The role and importance of empathy in clinical practice has been widely
      discussed. This paper focuses on the ideal of clinical empathy, as involving both
      cognitive understanding and affective resonance. I argue that this account is
      subject to a number of objections. Affective resonance may serve more as a
      liability than as a benefit in clinical settings, and utilizing this capacity is
      not clearly supported by the relevant empirical literature. Instead, I argue that
      the ideal account of empathy in medicine remains cognitive, though there is a
      central role for expressing empathic concern toward patients.

PMID- 30238182
TI  - Probiotic intervention in infancy is not associated with development of beta cell
      autoimmunity and type 1 diabetes.

PMID- 30238183
TI  - Managing Women with Sexual Dysfunction: Difficulties Experienced by Malaysian
      Family Physicians.
AB  - Recognizing barriers to managing sexual issues makes it more likely that
      effective ways to overcome them will be found. In Malaysia, where discussion of
      sexual issues is taboo, sociocultural factors may influence how physicians manage
      patients with these types of problems. This article focuses on the challenges
      encountered by 21 Malay family physicians when women experiencing sexual problems
      and female sexual dysfunction (FSD) attended their clinics, an uncommon
      occurrence in Malaysia, despite their high prevalence. This qualitative study
      employed a phenomenological framework and conducted face-to-face in-depth
      interviews. Three main barriers to managing women with sexual problems were
      identified that can hinder assessment and treatment: insufficient knowledge and
      training; unfavorable clinic environments; and personal embarrassment. Some
      barriers were associated with physician characteristics but many were systemic.
      These were further evaluated using social cognitive theory. Professional
      attitudes appear important as those physicians with an interest in managing
      women's health seemed to make greater effort to explore issues further and work
      to gain trust. Physicians who appeared indifferent to the impact of FSD showed
      greater reluctance to find solutions. Systemic issues included unfavorable
      clinical settings, lack of training, and lack of local evidence. Any strategy to
      address FSD needs to be underpinned by appropriate policies and resources.

PMID- 30238184
TI  - Approach and Avoidance Biases Toward Sexual Stimuli and Their Association with
      the Dual Control Model of Sexual Response in Heterosexual Men.
AB  - Many models of human behavior work in an interaction of a dual system. While one
      system usually represents controlled and reflective behavioral responses, the
      other system reflects automatic and impulsive actions. In the impulsive system,
      positive stimuli initiate approach reactions and negative cues avoidance
      reactions. Besides stimulus valence, the behavioral response triggered by the
      impulsive system is influenced by personality (e.g., the propensity to react with
      approach or avoidance biases in a specific situation). The present study applied
      a computerized Approach-Avoidance Task (AAT; Rinck & Becker, 2007) to assess
      automatic behavioral approach and avoidance biases toward sexual and neutral
      stimuli in heterosexual men (N = 40). Individual AAT-performance was furthermore
      related to sexual excitation (SES) and the two sexual inhibition factors (SIS1
      and SIS2) as proposed by the Dual Control Model of sexual response (Bancroft &
      Janssen, 2000). Against our hypotheses, participants did not show a stronger
      approach bias toward sexually preferred (i.e., images of women) than sexually not
      preferred stimuli (i.e., images of men or children). However, stronger approach
      biases toward images of women were positively associated with sexual excitation
      and negatively correlated with sexual inhibition due to a threat of performance
      failure (SIS1) even after controlling for potential confounds (i.e., general
      behavioral activation and inhibition). The results support the importance of the
      influence of dispositional traits measured with the Dual Control Model of sexual
      response on approach and avoidance biases toward sexually preferred stimuli in
      heterosexual men.

PMID- 30238185
TI  - YouTube as a source of information in retinopathy of prematurity.
AB  - AIM: We aimed to evaluate the quality of information available on YouTube
      regarding the basic information, examination, diagnosis, and the treatment of
      retinopathy of prematurity (ROP). METHODS: A YouTube search was performed on
      https://www.youtube.com / for videos pertaining to "retinopathy of prematurity"
      and "ROP." The first 100 relevant videos were included in the study. Two
      ophthalmologist reviewers independently evaluated and classified the videos as
      useful or misleading. The videos were accepted as "useful," if they provide
      scientifically correct information about any aspect of ROP: cause, pathogenesis,
      symptoms, findings, treatments, procedure details of the treatment, epidemiology,
      and prognosis. The videos contain scientifically unproven information are defined
      as "misleading." Videos were also classified according to the source:
      surgeon/practitioner, independent user, hospital/free clinic, social media/TV,
      medical site, university, and advertisement. RESULTS: The mean duration, the mean
      days on YouTube, the mean comments per videos, and the mean dislikes per video
      were similar in useful and misleading videos. However, the mean likes per day,
      mean view per video, and mean view per day were significantly higher in useful
      videos than those of misleading videos (p = 0.004, p = 0.022, and p = 0.011,
      respectively). Most of the useful videos were uploaded by healthcare
      professionals including source from university, hospital/free clinic, and
      surgeon/practitioner (48/64). The videos uploaded by healthcare professionals
      were more useful compared to those of non-healthcare professionals (p = 0.029).
      CONCLUSION: YouTube could be used as an important tool for patient information in
      ROP. However, one third of the YouTube videos regarding ROP are misleading and
      may present a risk of harmful consequences. In this aspect, authoritative videos
      by healthcare professionals should be uploaded for dissemination of reliable
      information on ROP.

PMID- 30238186
TI  - Efficacy and safety of new-generation transcatheter aortic valves: insights from
      the Israeli transcatheter aortic valve replacement registry.
AB  - AIM: To compare procedural outcomes of transcatheter aortic valve replacement
      (TAVR) patients treated with new-generation valves. METHODS: We performed a
      retrospective analysis on an Israeli multicenter registry comprised of four
      tertiary centers, comparing patient outcomes implanted with the Edwards SAPIEN S3
      (ES3) vs. the Medtronic Evolut R (MER) valves. RESULTS: The study population
      included 735 patients (ES3 n = 223; MER n = 512). The use of MER was
      significantly associated (p < 0.05) with higher rates of post-dilatation (35% vs.
      10%), and the need for a second valve (2.7% vs. 0.5%). Procedural device success
      was comparable between groups (97% vs. 98%, p = 0.76); however, moderate
      angiographic paravalvular leak was higher (3.3% vs. 0.5%, p = 0.027) for MER vs.
      ES3, respectively. As compared to MER, 1 month echocardiography revealed higher
      peak and mean aortic valve gradients for ES3 (12/6 vs. 17/10 mmHg, p < 0.001,
      respectively). While the safety outcome at 1 month was lower for MER (8.8% vs.
      13.9%, p = 0.035), similar 1-month, 1-year, and 3-year all-cause mortality were
      observed (1.9% vs. 1.3%; 8% vs. 8.5%, and 9.7 vs. 10.3%, for MER vs. ES3,
      respectively). In a propensity score matching analysis, there was no difference
      in major outcomes between the groups, including device success and the 1 month
      safety outcome. CONCLUSION: Although favorable efficacy and safety clinical
      outcomes were observed in this large contemporary registry for both new
      generation devices used, some procedural and post-procedural outcomes differ
      significantly between the two valves.

PMID- 30238187
TI  - Ellipsomyxa arariensis n. sp. (Myxozoa: Ceratomyxidae), a new myxozoan parasite
      of Pygocentrus nattereri Kner, 1858 (Teleostei: Characidae) and Pimelodus ornatus
      Kner, 1858 (Teleostei: Pimelodidae) from Marajo Island, in the Brazilian Amazon
      region.
AB  - Ellipsomyxa arariensis n. sp. was found in the gallbladder of Pygocentrus
      nattereri Kner, 1858 and Pimelodus ornatus Kner, 1858 from the Arari River on
      Marajo Island in Para, Brazil. The new species has disporous plasmodium that
      varies in size and shape, with ellipsoidal mature spores in the sutural view that
      have a curved suture line. The spores are 12.6 (12.0-13.4) MUm in length and 7.3
      (6.7-8.0) MUm in width. The two polar capsules present in the spore are pyriform
      and of equal size, with subterminal openings that project in opposite directions.
      The polar capsules are 3.5 (3.4-4.0) MUm long and 2.6 (2.5-3.2) MUm wide. Based
      on the partial sequences of the SSU rRNA gene of the Ellipsomyxa arariensis n.
      sp. spores found in Pygocentrus nattereri Kner, 1858 (1325 bps) and Pimelodus
      ornatus Kner, 1858 (1240 bps), the new species is clearly distinct from all the
      other myxozoan sequences deposited in GenBank. Based on Bayesian inference and p
      distances, the new species belongs to the "Ellipsomyxa clade", together with all
      the other Ellipsomxa species, reinforcing the monophyletic status of this genus.
      Overall, the morphological data and the partial sequences of the SSU rRNA gene
      provide a conclusive diagnosis of Ellipsomyxa arariensis n. sp. as a species
      distinct from all the other Ellipsomyxa species described previously.

PMID- 30238188
TI  - The development of Cryptocaryon irritans in a less susceptible host rabbitfish,
      Siganus oramin.
AB  - Cryptocaryon irritans is a ciliated protozoan parasite infecting the gills and
      skin of almost all marine teleosts, resulting in severe disease. Notably, C.
      irritans is unable to cause significant pathogenesis in rabbitfish, Siganus
      oramin, a well-known less susceptible host. However, little is known about the
      development of C. irritans in rabbitfish. Thus, in the present study, rabbitfish
      were artificially infected with C. irritans at a 1/2 maximal tolerance dose
      (MTD), using the susceptible host, large yellow croaker, Larimichthys crocea, as
      a control. The daily food consumption (DFC), survival, and relative infection
      intensity (RII) of the fish were observed, and the relative number of tomonts
      (RNT), reproductive rate, and characteristics of C. irritans tomonts were
      measured. The lethal concentration 50 (LC50) of C. irritans on rabbitfish and
      large yellow croaker was 2236, and 264 theronts/g fish, respectively. The DFC of
      rabbitfish decreased by 14.6% at day 1 post-C. irritans infection (PI), but
      immediately returned to normal DFC levels by day 2 PI, and was not affected by
      secondary infection. However, large yellow croaker stopped feeding at day 3 PI,
      and all fish died following secondary infection with C. irritans. The RII of
      rabbitfish exhibited a significant downward trend at 6 h PI, and the reproductive
      rate of C. irritans was 8%; in contrast, the RII of large yellow croaker was not
      significantly different from 0 to 72 h PI, and the reproductive rate of C.
      irritans reached to 59.05-fold. Over the same time frame, the diameter of tomonts
      from rabbitfish was smaller compared with those from large yellow croaker. These
      results indicated that the rabbitfish were somehow able to limit the development
      of C. irritans, such that most trophonts left the host during early developmental
      stages, whereas those that survive could only develop into small tomonts.

PMID- 30238191
TI  - Light-induced ATP release from the lens.
AB  - The recent discovery of the photoreceptor melanopsin in lens epithelial cells has
      opened the possibility of modulating this protein by light stimulation.
      Experiments carried out on New Zealand white rabbits have demonstrated that the
      release of ATP from the lens to the aqueous humor can be reduced either when a
      yellow filter or a melanopsin antagonist is used. Compared to control (1.10 +/-
      0.15 MUM ATP), the application of a yellow filter (lambda465-480) reduced ATP in
      the aqueous humor 70%, while the melanopsin antagonist AA92593 reduced the
      presence of ATP 63% (n = 5), an effect which was also obtained with the PLC
      inhibitor U73122. These results indicate that when melanopsin is blocked either
      by the lack of light, a filter, or an antagonist, the extracellular presence of
      ATP is significantly reduced. This discovery may be relevant, on the one hand,
      because many ocular physiological processes are controlled by ATP and, on the
      other hand, because it is possible to stimulate ATP release with just light and
      without using any added substance.

PMID- 30238189
TI  - Flare levels after intravitreal injection of ranibizumab, aflibercept, or
      triamcinolone acetonide for diabetic macular edema.
AB  - PURPOSE: To evaluate anterior flare intensity (AFI) and central retinal thickness
      (CRT) values after intravitreal injection of aflibercept (IVA), ranibizumab
      (IVR), or triamcinolone acetonide (IVTA) in patients with diabetic macular edema
      (DME). METHODS: This research was conducted as a prospective study for patients
      with DME. Patients with phakia received either IVA or IVR, whereas patients with
      pseudophakia received IVA, IVR, or IVTA. AFI and CRT were measured using a laser
      flare meter and spectral domain optical coherence tomography, respectively, at
      days 0, 1, 7, 30, and 90. RESULTS: Forty patients with phakia and 60 patients
      with pseudophakia were enrolled this study. In the IVTA group, AFI of
      pseudophakic eyes was significantly decreased at days 1 (p = 0.0487), 7 (p =
      0.0201), and 30 (p = 0.0211). In the IVA group, AFI of phakic eyes was
      transiently increased at day 1 (p = 0.0078) and returned to baseline at day 7,
      whereas no significant change was observed in AFI of pseudophakic eyes. In the
      IVR group, there was no significant change in AFI regardless of phakic condition.
      All groups showed significant reduction in CRT at day 7 and later. CONCLUSION:
      DME improved after treatment by IVTA, IVR, or IVA, whereas AFI was reduced only
      in eyes treated with IVTA. The temporal profiles of AFI are likely related to
      differences in the pharmacological properties of the drugs.

PMID- 30238190
TI  - Long-term follow-up of pachychoroid pigment epitheliopathy and lesion
      characteristics.
AB  - AIMS: To investigate conversion of pachychoroid pigment epitheliopathy (PPE)
      lesions and the development of other pachychoroid spectrum diseases in patients
      with PPE during follow-up. METHODS: We retrospectively reviewed medical records
      of 46 eyes of 44 patients who had a diagnosis of PPE and were followed up for at
      least 3 years. RESULTS: Eyes with PPE (17.4%) developed central serous
      chorioretinopathy (CSC), and none developed pachychoroid neovasculopathy or
      polypoidal choroidal vasculopathy. Of 74 initial PPE lesions, 21.6% were retinal
      pigment epithelium (RPE) thickening, 36.5% were pigment epithelium detachment
      (PED), and 41.9% were RPE elevation with microbreak appearance (REwM). Five
      (62.5%) of the eight initial PPE lesions progressing to CSC were REwM. Two
      developed directly from the REwM and three REwMs transformed to PED first, and
      then progressed to CSC. Three initial PEDs progressed to CSC. REwMs can also
      transform to PED and RPE thickening. No initial PEDs or RPE thickenings
      transformed to a REwM. Of the new PPE lesions, 60% were REwM, 26.7% were PEDs,
      and 13.3% were RPE thickening. CONCLUSION: The smallest PPE lesion that can be
      detected is a REwM of RPE. It may be the precursor lesion for pachychoroid
      spectrum disease, but further large-scale prospective studies are required.

PMID- 30238192
TI  - Electrospray Generated from the Tip-Sealed Fine Glass Capillary Inserted with an
      Acupuncture Needle Electrode.
AB  - In electrospray, excess charges are supplied to a sample solution by the
      occurrence of electrochemical reactions. Recently, different versions of
      electrospray, e.g., dielectric barrier electrospray ionization, inductive
      desorption electrospray ionization, and electrostatic-ionization driven by
      dielectric polarization, have been reported in which the sample solution was not
      in direct contact with the metal electrode but separated by dielectric materials.
      The objective of the current work is to elucidate the mechanism of dielectric
      barrier electrospray. A sealed borosilicate glass capillary inserted with a fine
      acupuncture needle was used as a probe. A sample solution (~ 400 nL) was captured
      on the glass capillary tip and a positive high voltage (HV) pulse (+ 4.5 kV) was
      applied to the internal metal electrode. Mass spectra were measured as a function
      of the HV pulse width from MUs to 10 s. Ions started to be detected with the
      pulse width of ~ 5 ms. The ion intensities increased slowly with time and reached
      a plateau in a few seconds. The charge distribution of cytochrome c [M + nH]n+
      shifted to higher n values from a few ms to seconds. In addition to cone-jet mode
      normal electrospray that lasted until all the liquid sample was depleted from the
      glass tip, the polarization-induced electrospray ionization was observed at the
      early stage of the HV application. Graphical Abstract ?.

PMID- 30238193
TI  - Study of Photocatalytic Nano-Particle Effects on the Low Temperature Plasma
      Ionization Mass Spectrometry.
AB  - Although the low temperature plasma mass spectrometry (LTP-MS) is widely used as
      an analysis tool for many biochemical samples, its application window is somehow
      limited to the analytes of low molecular mass and high volatility. For this
      reason, there have been attempts to enhance the ionization/desorption
      efficiencies with extra heating, for instance. In this study, another enhancement
      method was suggested using the photocatalytic nano-particles (NPs). In order to
      assess the NP effects on the LTP-MS, two fatty acid ethyl ester samples of ethyl
      myristate and ethyl palmitate were used, and the NP of titanium dioxide (TiO2)
      was mainly employed. The results showed that the signal intensities of the LTP-MS
      were largely increased with the TiO2 addition for both samples. In addition, the
      cholesterol sample was analyzed using the TiO2 assisted LTP-MS, also resulting in
      the enhancement of the signal intensity. The overall results inferred that the
      photocatalytic NP confirmed its role as an effective assist tool for the LTP-MS,
      especially suitable because of the facile method and the heat-free nature.
      Graphical Abstract ?.

PMID- 30238194
TI  - A nanocomposite probe consisting of carbon quantum dots and phosphotungstic acid
      for fluorometric determination of chromate(VI) with improved selectivity.
AB  - A fluorometric quenching assay is described for the determination of chromate(VI)
      by using a nanocomposite probe consisting of carbon quantum dots (CQDs) and
      phosphotungstic acid (HPW). The stable nanoprobe was synthesized via hydrothermal
      carbonization of glucose in the presence of HPW. HPW promotes the dehydration and
      carbonization and acts as an "electronic receptor". It blocks the radiative
      electron/hole recombination in the CQDs and leads to a product whose fluorescence
      (with excitation/emission peaks at 360/463 nm) is quenched. The CQD/HPW was
      characterized by transmission electron microscopy, FT-IR spectroscopy, X-ray
      photoelectron spectroscopy, Raman spectroscopy, UV-vis absorption and
      fluorescence spectroscopy to characterize their surface morphology, functional
      groups and elemental composition, crystal structure and optical properties. The
      nanocomposite is nearly mono-disperse with an average particle diameter of 1.7
      nm, and displays excitation wavelength-dependent and pH-dependent
      photoluminescence. Fluorescence drops on addition of chromate(VI) due to an inner
      filter effect. The ability of receiving electron for HPW can hinder the electron
      transfer from CQD/HPW to other metal ions, so the nanocomposite showed excellent
      selectivity towards chromate(VI). Fluorescence drops linearly with the
      concentration of chromate(VI) in the range from 2 to 80 MUM, with a limit of
      detection of 0.16 MUM. Graphical abstract Hydrothermal carbonization preparation
      of carbon quantum dots and phosphotungstic acid nanocomposite probe for
      fluorometric determination of chromate(VI) based on inner filter effect.

PMID- 30238196
TI  - Enhanced Computational Model for Gravitational Search Optimized Echo State Neural
      Networks Based Oral Cancer Detection.
AB  - The Clinical Oncology of American Society report in 2016 predicted deaths are
      increased upto 9570 due to oral cancer. This cancer occurs due to abnormal tissue
      growth in the oral cavity. This cancer has limited symptoms, so, it has been
      difficult to recognize in the early stages. To reduce the death rate of this oral
      cavity cancer, an automatic system has been developed by applying the
      optimization techniques in both image processing and machine learning techniques.
      Even though these methods are successfully recognizing the cancer, the detection
      accuracy is still one of the major issues because of complex oral tissue
      structure. So, this paper introduces the Gravitational Search Optimized Echo
      state neural networks for predicting the oral cancer with effective manner.
      Initially the X-ray images are collected from the oral cancer database which
      contains several noises that has to be eliminated with the help of the adaptive
      wiener filter. Then the affected part has been segmented with the help of the
      enhanced Markov Stimulated Annealing and the features are derived from segmented
      region. The derived features are analyzed with the help of the proposed
      classifier. The excellence of the oral cancer detection system is evaluated using
      simulation results.

PMID- 30238195
TI  - Immunotherapy for Merkel Cell Carcinoma.
AB  - OPINION STATEMENT: Merkel cell carcinoma (MCC) is a rare but highly aggressive
      neuroendocrine carcinoma of the skin, with frequent recurrences, metastasis, and
      a high mortality rate. For primary or locoregional MCC, a wide local excision
      followed by radiation therapy is the basic treatment modality for preventing
      recurrence at the primary site and involved lymph nodes. Cytotoxic chemotherapy
      has been commonly used to treat patients with metastatic MCC, but not as an
      adjuvant therapy for high-risk resected MCC. Although MCC is often chemotherapy
      sensitive in the first-line setting, responses are rarely durable and most
      patients subsequently relapse and develop metastasis. Treatment with checkpoint
      inhibitors (CPIs) has shown a major advancement in the treatment of advanced MCC.
      Systemic therapy against programmed cell death-1/programmed cell death ligand-1
      (PD-1/PD-L1) is associated with a high objective response rate (ORR), prolonged
      durable responses, and good tolerability in advanced-stage MCC. CPIs are now
      included in the National Comprehensive Cancer Network (NCCN) guidelines for the
      treatment of patients with metastatic MCC. Multiple clinical trials of CPIs
      administered as monotherapy or in combination with other agents or modalities,
      including the adjuvant setting, are ongoing. Immunotherapy offers a promising
      future for patients with MCC. In this review, we present an overview of emerging
      data on immunotherapy, especially CPIs of the PD-1/PD-L1 pathway, for patients
      with advanced MCC.

PMID- 30238197
TI  - Conspicuous activated lymphocytic proliferation associated with cytokine-release
      syndrome after CAR T-cell therapy.

PMID- 30238199
TI  - Optimal PPI Dosing for Improving GERD Symptoms: Is Timing Everything?

PMID- 30238200
TI  - Antithrombotic Treatment Is Associated with Small-Bowel Video Capsule Endoscopy
      Positive Findings in Obscure Gastrointestinal Bleeding: A Systematic Review and
      Meta-Analysis.
AB  - INTRODUCTION: The impact of antithrombotic treatment on the findings of small
      bowel capsule endoscopy for patients with obscure gastrointestinal bleeding
      remains contentious. We aimed to determine the effect of these agents on small
      bowel video capsule endoscopy positive findings. METHODS: MEDLINE, Cochrane
      Library, and Google Scholar were searched for studies reporting on patients
      receiving concurrent antithrombotic treatment, while undergoing capsule endoscopy
      for obscure gastrointestinal bleeding (OGIB). Outcomes were the effect of
      antithrombotic therapy-overall and per type of antithrombotic agent-on the
      examination's positive findings and re-bleeding risk. The effect size of study
      outcomes is presented as odds ratio (OR) with 95% confidence interval (CI).
      RESULTS: Fourteen studies with 1023 patients were included. We detected
      significant heterogeneity with no evidence of publication bias. Compared to
      antithrombotic drug nonusers, antithrombotic treatment was associated with an
      increased prevalence of positive findings [OR 1.98 (95% CI 1.34-2.93); P =
      0.0006]. This effect did not differ between antiplatelet and anticoagulant
      treatments [OR 2.22 (95% CI 1.28-3.84); P = 0.005 and 2.53 (95% CI 1.66-3.87); P
      < 0.0001, respectively]. Antithrombotic use over no use was not associated either
      with overt [OR 1.17 (95% CI 0.51-2.66); P = 0.71] or with occult [OR 0.86 (95% CI
      0.38-1.95); P = 0.71] bleeding pattern. However, concurrent antithrombotic
      treatment was associated with higher odds for re-bleeding compared to no
      treatment [OR 2.53 (95% CI 1.46-4.37); P = 0.0009]. CONCLUSIONS: Antithrombotic
      treatment is associated with more positive findings in small-bowel video capsule
      endoscopy in OGIB as well as higher odds of re-bleeding.

PMID- 30238198
TI  - Long-term outcomes in patients treated in the intensive care unit after
      hematopoietic stem cell transplantation.
AB  - The number of patients who are successfully discharged from the intensive care
      unit (ICU) after hematopoietic stem cell transplantation (HSCT) remains limited.
      Most previous studies have evaluated short-term outcomes using ICU mortality;
      there have been comparatively fewer reports of long-term outcomes. We
      retrospectively analyzed 39 HSCT patients admitted to the ICU for the first time
      between April 2008 and July 2014. Performance status was evaluated in four long
      term survivors in July 2016. Median age at ICU admission was 54 years (range 30
      68). In total, 33 patients (70.2%) required mechanical ventilation and 31
      patients (66%) required dialysis. The median OS from first ICU admission was 41
      days (95% confidence interval [CI]: 22-64) and the 1-year survival rate was 12.8%
      (95% CI 4.7-25.2). No statistically significant factors were associated with
      short-term outcomes. Among long-term outcomes, a second or subsequent HSCT and
      neutropenia at ICU admission were significant risk factors. Four of 10 ICU
      survivors have survived with good performance status for a median of 1994 (1203
      2633) days. Our results suggest that the number of prior transplants and
      neutropenia at ICU admission may influence OS.

PMID- 30238201
TI  - Biliary Decompression in Perihilar Cholangiocarcinoma Improves Survival: A Single
      Center Retrospective Analysis.
AB  - BACKGROUND AND AIMS: The complex biliary strictures of perihilar
      cholangiocarcinoma present significant challenges for providing adequate and long
      lasting biliary drainage. The best approach to relieve obstruction remains
      controversial. The purpose of this study was to assess stenting outcomes in
      perihilar cholangiocarcinoma. METHODS: This study was approved by the center's
      institutional review board. Subjects with a diagnosis of perihilar
      cholangiocarcinoma who underwent endoscopic retrograde cholangiopancreatography
      (ERCP) were identified from endoscopic and pathologic databases from 1997 to
      2014. Patient characteristics, endoscopic data, and follow-up evaluation data
      were retrospectively collected via review of available medical records. RESULTS:
      A total of 199 patients with perihilar cholangiocarcinoma who underwent a total
      of 504 ERCPs were included in the study. Nine of 504 (1.8%) procedures were
      technical failures. Among the 495 technically successful procedures, 347 (70.1%)
      procedures were clinical successes. Clinical success was significantly associated
      with longer overall survival (HR 0.57; p = 0.002). A higher proportion of
      patients with bilateral drainage had clinical success, compared with those with
      unilateral drainage. Cholangitis was not more common in the bilateral group
      compared to the unilateral group except in the group where a segment was not
      drained (1.9% vs 1.6% vs 7.1%, respectively). Patients with metal stents were 3.8
      times more likely to have clinical success than those with plastic stents.
      CONCLUSIONS: In conclusion, adequate biliary drainage improves overall survival.
      Bilateral stenting if anatomy permits with self-expanding metal stents rather
      than plastic stents appears to provide the optimal chance of clinical success.

PMID- 30238203
TI  - A Comparison Between Community and Academic Practices in the USA in the
      Management of Chronic Hepatitis B Patients Receiving Entecavir: Results of the
      ENUMERATE Study.
AB  - BACKGROUND AND AIMS: The management of chronic hepatitis B patients is not well
      characterized in real-world practice. We compared baseline characteristics of CHB
      patients on entecavir, the frequency of on-treatment monitoring, and the
      effectiveness of ETV treatment between academic and community practices. METHODS:
      Treatment-naive CHB patients >=18 years old, treated with ETV for >=12 months
      from 2005 to 2013, in 26 community and academic practices throughout the USA were
      retrospectively evaluated. RESULTS: Of 841 patients enrolled, 658 (65% male, 83%
      Asian, median age 47, 9% with cirrhosis) met inclusion criteria. Half of the
      patients (52%) were from community practices. A lower percentage of patients in
      community practices had cirrhosis or liver cancer (5 vs. 14%). Community
      practices more often treated patients with baseline ALT < 2 * ULN. Over a median
      follow-up of 4 years, community practices were more likely to discontinue ETV
      with less frequent laboratory monitoring compared to academic practices. The 5
      year cumulative probability of ALT normalization was greater among patients
      treated in community practices (70 vs. 50%, p < 0.001), but the 5-year cumulative
      probability of undetectable HBV DNA was lower (45 vs. 70%, p < 0.001) than those
      treated in academic practices. CONCLUSION: Academic practices saw CHB patients
      with more advanced liver disease, more often followed AASLD guidelines, and
      monitored patients on ETV treatment more frequently than community practices.
      While patients in community practices were less likely to achieve undetectable
      HBV DNA and more likely to achieve ALT normalization, the rates of HBeAg loss and
      seroconversion as well as HBsAg loss were similar.

PMID- 30238202
TI  - Microbial Biomarkers in Patients with Nonresponsive Celiac Disease.
AB  - BACKGROUND AND AIMS: In nonresponsive celiac disease (NRCD), the symptoms and
      duodenal damage persist despite a gluten-free diet. Celiac disease patients with
      persistent symptoms are found to have a dysbiotic microbiota. We thus
      hypothesized that increased seroreactivity to the serum gluten-sensitive
      microbial antibodies Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens
      associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane
      protein (OmpW) is associated with NRCD. METHODS: ASCA, I2 and OmpW were measured
      in 20 seronegative CD patients with persistent villous damage despite strict
      dietary treatment (NRCD group). Fifty-eight responsive patients served as CD
      controls (55 on gluten-free treatment) and 80 blood donors as non-CD controls.
      RESULTS: At least one microbial marker was positive in 80% of NRCD patients, in
      97% of untreated CD and 87% of treated CD patients, and in 44% of controls. NRCD
      patients had the highest frequency of ASCA positivity (65% vs 52, 20, and 0%,
      respectively) and also significantly higher ASCA IgA (median 14.5 U/ml) and IgG
      (32.5 U/ml) titers than treated CD patients (7.0 U/ml, 13.0 U/ml) and non-CD
      controls (4.5 U/ml, 5.8 U/ml). The frequencies of I2 and OmpW were lower in NRCD
      than in untreated CD (65% and 45% vs 86% and 59%, respectively), and I2 titers
      were higher in NRCD (median absorbance 0.76) and untreated (1.0) and treated
      (0.83) CD than controls (0.32). OmpW was elevated in untreated (1.1) and treated
      (0.94) CD patients compared with controls (0.79). CONCLUSIONS: Seropositivity and
      high titers of ASCA are associated with NRCD and might serve as an additional
      follow-up tool in CD.

PMID- 30238204
TI  - Flavobacterium dasani sp. nov., a psychrotolerant bacterium isolated from Arctic
      soil.
AB  - A novel yellow-colored, Gram-stain-negative, aerobic, non-motile, catalase- and
      oxidase-positive, and rod-shaped psychrotolerant bacterium, designated strain PLR
      18-3T, was isolated from Arctic soil and was subjected to polyphasic taxonomic
      study. Cells were able to grow at 0-30  degrees C, pH 6.0-10.5, and 0-3.0% (w/v)
      NaCl concentration. Based on the 16S rRNA gene sequence analysis, this Arctic
      strain belonged to the genus Flavobacterium, with the closest neighbor being
      Flavobacterium noncentrifugens R-HLS-17T (96.2% sequence similarity). The strain
      contained MK-6 as a sole respiratory quinone, phosphatidylethanolamine as the
      major polar lipid, and summed feature 3 (C16:1omega7c and/or C16:1omega6c), iso
      C15:0, iso-C15:0 G, iso-C17:0 3-OH, iso-C15:0 3-OH, anteiso-C15:0, and summed
      feature 9 (iso-C17:1omega9c and/or C16:010-methyl) as the predominant fatty
      acids. The DNA G + C content was 37.9 mol%. On the basis of polyphasic data,
      strain PLR-18-3T represents a novel species of the genus Flavobacterium, for
      which the name Flavobacterium dasani sp. nov. is proposed. The type strain is PLR
      18-3T (=KEMB 9005-713T=KACC 19627T=NBRC 113347T).

PMID- 30238205
TI  - Translocation of small molecules through engineered outer-membrane channels from
      Gram-negative bacteria.
AB  - Selective permeability is a key feature of biological membranes. It is controlled
      by the physico-chemical properties of the lipid bilayer and by channel-forming
      membrane proteins. Here we focus on the permeation of small molecules across
      channel-forming proteins in Gram-negative bacteria called porins and present a
      new approach based on artificial amino acids. We introduced Hco, a fluorescent
      amino acid with characteristic excitation and emission wavelengths, into OmpF and
      measured FRET from Hco to dissolved Bocillin FL using solubilized OmpF porins. We
      examined four variants of OmpF and by doing so, we were able to show that small
      molecules, like Bocillin FL, are remaining long enough in the porin in order to
      undergo FRET and produce a reproducible fluorescence signal. This finding opens
      the way to quantify translocation in the future by the simultaneous detection of
      resistive pulses and differential fluorescence with FRET as an example.

PMID- 30238207
TI  - Cerebral white matter Hyperintensities in HIV-positive patients.
AB  - White matter hyperintensities (WMHs) have been associated with neurological
      complications including cognitive impairment. WMHs have been often described in
      HIV positive subjects and they have been linked to neurocognitive impairment,
      cerebrospinal fluid (CSF) residual viral replication and biomarkers of monocyte
      activation. Aim of this study was to grade WMHs in HIV-positive individuals using
      a simple visual scale and to explore their severity with clinical, neurocognitive
      and biomarker characteristics. Brain MRIs were retrospectively evaluated by two
      reviewers who rated WMHs following the "age-related white matter changes (ARWMC)"
      scale. 107 adult HIV-positive patients receiving lumbar punctures for clinical
      reasons were included. 70 patients (66.6%) were diagnosed with WMHs. Average WMH
      scores were higher in treated [7 (1-11)] vs. naive individuals [3 (0-6)] (p =
      0.008). Higher WHMs scores were observed in patients with chronic renal
      impairment along with chronic hepatitis (naive) and longer HIV duration (treated
      participants). No consistent associations between plasma, CSF biomarkers and WMHs
      scores were found. 45 patients underwent full neurocognitive tests and WMHs
      scores were non-significantly higher in patients diagnosed with HAND [6.5 (0.5
      8.3) vs. 1.5 (0-7), p = 0.165]; screening (IHDS and FAB), visuo-spatial (Corsi's)
      and auditory-verbal memory (disillabic words repetition) tests scored worse in
      patients with higher WMHs. In our population of HIV-positive patients with low
      CD4 nadir and partial CD4 cell recovery the burden of WMHs was associated with
      the duration of HIV infection and with commonly observed comorbidities (such as
      renal and hepatic impairment). Given the association with worse neurocognition,
      further studies on tailored interventions are needed.

PMID- 30238206
TI  - Occurrence, Risk Factors, Prognosis and Prevention of Swimming-Induced Pulmonary
      Oedema: a Systematic Review.
AB  - BACKGROUND: Swimming-induced pulmonary oedema (SIPE) can affect people with no
      underlying health problems, but may be life threatening and is poorly understood.
      The aim of this systematic review was to synthesise the evidence on SIPE
      incidence, prevalence, risk factors, short- and long-term outcomes, recurrence
      and effectiveness of interventions to prevent recurrences. METHODS: We carried
      out a literature search using bibliographic databases and reference lists. Risk
      of bias was assessed by adapting existing quality assessment tools including
      those developed by the National Heart Lung and Blood Institute. RESULTS: Nine
      studies met the inclusion criteria. Quantitative synthesis was not possible
      because of study heterogeneity. Five studies, which differed from each other in
      case definition, swimming environment, population characteristics and
      denominators, reported an incidence of 0.01% of UK triathlons raced over 5 years
      in unspecified swimming environments (one study, not fully reported, of men and
      women of unspecified age); 0.5% of river races swum over 3 days in Sweden (one
      study, of men and women up to the age of 70); and 1.8-26.7% of time trials in the
      sea around Israel (three studies of male teenage military trainees). One study
      reported that 1.4% of triathletes in the USA had experienced SIPE. One study
      found that hypertension, female sex, fish oil use, long course distance and
      another lower initial lung volumes and flows were risk factors for SIPE. A third
      study reported that higher mean pulmonary artery pressures and pulmonary artery
      wedge pressures, and lower tidal volumes were associated with SIPE. Three studies
      suggested that SIPE symptoms usually resolve within 24 h, although a restrictive
      deficit in lung function persisted for a week in one small study. We found no
      studies that reported deaths from SIPE. The single small study of longer-term
      outcomes reported no difference between affected and unaffected swimmers. Two
      studies suggested that around 30% of people report recurrences of SIPE. Two very
      small uncontrolled studies of the effect of sildenafil for recurrence prevention
      were inconclusive. CONCLUSIONS: SIPE may be an important public health problem
      affecting the growing number of recreational open water swimmers. Further
      research should clarify the frequency of SIPE among recreational open water
      swimmers, confirm reported risk factors and explore others, explore long-term
      consequences and test interventions to prevent recurrences.

PMID- 30238208
TI  - Neural correlates of apathy in patients with neurodegenerative disorders: an
      activation likelihood estimation (ALE) meta-analysis.
AB  - Apathy is commonly reported in Alzheimer's Disease (AD), Fronto-Temporal Dementia
      (FTD) and Parkinson's Disease (PD). In our meta-analysis we analysed a total of
      41 studies to identify brain patterns associated with apathy. For these purposes
      we used activation likelihood estimation meta-analyses. Our main overall analysis
      showed that apathy is associated to hypometabolism and a decreased gray matter
      volume in the left inferior frontal gyrus (BA 45, 46). Disorder-specific
      analyses, not performed by means of meta-analysis, because of the small number of
      studies, but by means a label-based review, revealed an altered brain perfusion
      and decreased gray matter volume in anterior cingulate cortex (BA 24, 32) in AD
      patients and a decreased gray matter volume in inferior frontal gyrus (BA 44, 45)
      and parietal cortex (BA 40) in FTD patients. These findings suggest that apathy
      is mainly associated with a cortical dysfunction of areas involved in executive
      cognitive processing (i.e. action planning) and emotional regulation (auto
      activation and reward processing). Knowledge about the neural underpinnings of
      apathy is crucial for understanding its clinical characteristics in
      neurodegenerative diseases and for developing novel strategies of treatment in
      clinical practice.

PMID- 30238209
TI  - Ipsilateral somatosensory responses in humans: the tonic activity of SII and
      posterior insular cortex.
AB  - In the present study, we mapped the spatio-temporal dynamics of cortical
      responses to ipsilateral median nerve stimulation using intracerebral recordings
      (stereo-EEG) in 38 drug-resistant epileptic patients. Furthermore, we compared
      the pattern of responsiveness obtained in the same leads across ipsilateral and
      contralateral stimulations. Ipsilateral responses were found mostly confined to
      SII and posterior insula, while no activity was found in ipsilateral SI. By
      examining the temporal profiles of activation, ipsilateral SII showed a prominent
      tonic pattern, while contralateral SII exhibited both phasic and tonic responses.
      Beyond the localization of the active cortical nodes, these data contributed to
      identify the cortico-cortical connections carrying the somatosensory information
      to the ipsilateral hemisphere, with a major role of transcallosal projections
      from contralateral SII. In light of previous literature and of its localization,
      the functional role possibly covered by long lasting discharge in SII and insular
      cortex is also discussed. Overall, the presence of tonic activities was neglected
      so far due to the impossibility to identify deep sources along with a resolved
      description of their time course. The use of stereo-EEG, instead, allows one to
      achieve a four-dimensional characterization, complementing the classical view
      about the somatosensory system organization.

PMID- 30238210
TI  - Beta-blocker Therapy in Acute Coronary Syndromes: a Time-Trend Interpretation of
      Evolving Clinical Benefits : Editorial to: "The Use of Oral Beta-Blockers and
      Clinical Outcomes in Patients with Non-ST-Segment Elevation Acute Coronary
      Syndromes: a Long-Term Follow-up Study" by J.C. Nicolau et al.

PMID- 30238211
TI  - Excess vascular endothelial growth factor-A disrupts pericyte recruitment during
      blood vessel formation.
AB  - Pericyte investment into new blood vessels is essential for vascular development
      such that mis-regulation within this phase of vessel formation can contribute to
      numerous pathologies including arteriovenous and cerebrovascular malformations.
      It is critical therefore to illuminate how angiogenic signaling pathways
      intersect to regulate pericyte migration and investment. Here, we disrupted
      vascular endothelial growth factor-A (VEGF-A) signaling in ex vivo and in vitro
      models of sprouting angiogenesis, and found pericyte coverage to be compromised
      during VEGF-A perturbations. Pericytes had little to no expression of VEGF
      receptors, suggesting VEGF-A signaling defects affect endothelial cells directly
      but pericytes indirectly. Live imaging of ex vivo angiogenesis in mouse embryonic
      skin revealed limited pericyte migration during exposure to exogenous VEGF-A.
      During VEGF-A gain-of-function conditions, pericytes and endothelial cells
      displayed abnormal transcriptional changes within the platelet-derived growth
      factor-B (PDGF-B) and Notch pathways. To further test potential crosstalk between
      these pathways in pericytes, we stimulated embryonic pericytes with Notch ligands
      Delta-like 4 (Dll4) and Jagged-1 (Jag1) and found induction of Notch pathway
      activity but no changes in PDGF Receptor-beta (Pdgfrbeta) expression. In
      contrast, PDGFRbeta protein levels decreased with mis-regulated VEGF-A activity,
      observed in the effects on full-length PDGFRbeta and a truncated PDGFRbeta
      isoform generated by proteolytic cleavage or potentially by mRNA splicing.
      Overall, these observations support a model in which, during the initial stages
      of vascular development, pericyte distribution and coverage are indirectly
      affected by endothelial cell VEGF-A signaling and the downstream regulation of
      PDGF-B-PDGFRbeta dynamics, without substantial involvement of pericyte Notch
      signaling during these early stages.

PMID- 30238212
TI  - Reconstruction of root systems in Cryptomeria japonica using root point
      coordinates and diameters.
AB  - MAIN CONCLUSION: We developed simple algorithms for reconstructing tree root
      system architecture using only the root point coordinate and diameter, which can
      be systematically obtained without digging up the root systems. Root system
      architecture (RSA) is strongly related to various root functions of the tree. The
      aim of this study was to develop a three-dimensional (3D) RSA model using
      systematically obtained information on root locations and root diameters at the
      locations. We excavated root systems of Cryptomeria japonica and systematically
      obtained XYZ coordinates and root diameters using a 10-cm grid. We clarified the
      patterns of the root point connections and developed a reconstructed root system
      model. We found that the root diameters farther from the stump centre are
      smaller. Additionally, we found that the root lengths of the segments running
      between the base and the connected root point were smaller than those of other
      root segments, and the inner angle between the base and the stump and between the
      base and the connected root point was narrower than for the other pairs. The new
      RSA model developed according to these results had average accuracies of 0.64 and
      0.80 for estimates of total volume and length, respectively. The developed model
      can estimate 3D RSA using only root point data, which can be obtained without
      digging up root systems. This suggests a wide applicability of this model in root
      function evaluation.

PMID- 30238213
TI  - Analyzing the Impact of Bariatric Surgery in Kidney Function: a 2-Year
      Observational Study.
AB  - BACKGROUND: Obesity is an independent risk factor for chronic kidney disease
      (CKD). Our aims were: (1) to evaluate the impact of bariatric surgery (BS) on
      kidney function, (2) clarify the factors determining postoperative evolution of
      glomerular filtration rate (DeltaGFR) and urinary albumin-to-creatinine ratio
      (DeltaUACR), and (3) access the occurrence of oxalate-mediated renal
      complications. METHODS: We investigated a cohort of 1448 obese patients who
      underwent BS. Those with baseline-estimated GFR (eGFR0) < 30 mL/min or without
      information about the 2-year post-surgical eGFR (eGFR2) were excluded. RESULTS: A
      total of 725 patients were included. At baseline, 38(5.2%) had hyperfiltration
      with eGFR0 >= 125 mL/min/1.73m2 (G0), 492 (67.9%) had eGFR0 90-124 mL/min/1.73m2
      (G1), 178 (24.6%) had eGFR0 60-89 mL/min/1.73m2 (G2), and 17 (2.3%) had eGFR0 <
      60 mL/min/1.73m2 (G3). DeltaGFR significantly increased in 96.6% (DeltaGFR = 23.8
      (IQR 15.9-29.8)) and 82.4% (DeltaGFR = 18.6 (IQR 3.6-44.0)) of the subjects with
      G2 and G3 CKD, respectively (p < 0.001). The variables independently associated
      with DeltaGFR were baseline body mass index (BMI) (positively), high blood
      pressure (HBP) (negatively), and fasting plasma glucose (FPG) (negatively), as
      well as FPG variation (positively). An overall prevalence of high UACR (>= 30
      mg/g-1) of 17.9% was found, with 81.5% of these subjects presenting A2(30-300
      mg/g-1) and 18.5% A3(> 300 mg/g-1) UACR. UACR significantly decreased after BS (p
      < 0.001). Significant predictors of DeltaUACR were BMI, systolic blood pressure,
      and HbA1c. Urinary excretion of calcium oxalate crystals was found in 77(11.1%)
      patients, with only 1 presenting oxalate-mediated renal complications.
      CONCLUSIONS: DeltaGFR seems to be influenced by the initial kidney function, as
      it decreases in subjects with hyperfiltration but tends to increase in those with
      kidney dysfunction. These results suggest that BS is associated with improvement
      of kidney outcomes, without a significant increase in renal complications.

PMID- 30238215
TI  - Biography: Kamal Mahawar.

PMID- 30238214
TI  - Laparoscopic Conversion of a Vertical Banded Gastroplasty to a Sleeve Gastrectomy
      in a Morbidly Obese Patient with a Complicated Medical History.
AB  - PURPOSE: We present our technique for performing a laparoscopic conversion of
      vertical banded gastroplasty (VBG) to sleeve gastrectomy (SG) in a morbidly obese
      patient. MATERIALS AND METHODS: A 58-year-old female with history of
      hypertension, diabetes, and morbid obesity (BMI 41). She had initially undergone
      an open VBG (BMI 58) and cholecystectomy (2002) and subsequently underwent two
      laparotomies for small bowel obstructions and two open ventral hernia repairs.
      She initially presented for repair of her large ventral hernia; however, to
      minimize the risk of recurrence and complications during the abdominal wall
      reconstruction, she was referred first for surgical weight loss and scheduled for
      laparoscopic conversion of VBG to gastric bypass. RESULTS: Initial access was
      obtained using an Optiview trocar and significant amount of adhesions were noted
      to the omentum, abdominal wall, stomach, and liver, including dense interloop
      adhesions precluding us from proceeding with a gastric bypass, our initial choice
      for conversion. Adhesions were taken down with a LigaSure device and sharp
      dissection. The previous vertical staple line was identified endoscopically. The
      banded area was narrowed, but intact, so the Marlex ring was divided to allow
      space for the new SG staple line. Stapler firings were oriented to divide the
      stomach parallel to the lesser curve and through the middle of the prior EEA
      opening, then up towards the Angle of His. Using Endo Stitch, the entire staple
      line was oversewn in a Lembert fashion. There was no evidence of narrowing on
      repeat endoscopy and leak test was negative. CONCLUSIONS: This video demonstrates
      the feasibility and safety of one-step laparoscopic conversion of vertical banded
      gastroplasty to sleeve gastrectomy.

PMID- 30238216
TI  - Seven-Year Outcomes of Laproscopic Sleeve Gastectomy in Indian Patients with
      Different Classes of Obesity.
AB  - BACKGROUND: The aim of the study was to assess the long-term outcome in terms of
      weight loss and remission of comorbidities among the patients who had undergone
      LSG in an Indian setting. METHODS: This is a retrospective observational study of
      patients (BMI > 30 kg/m2) who underwent LSG having a minimum 6 months of follow
      up data. Based on preoperative BMI, patients were grouped as class 1, 30 < BMI <
      35 kg/m2; class 2, 35 < BMI < 40 kg/m2; and class 3, BMI > 40 kg/m2. Data on BMI
      and %EWL between three classes and among genders at different follow-up points
      for 7 years were compared. RESULT: Study included 95 patients (mean age of 33.7
      +/- 11 years), and the preoperative mean BMI was 40.2 +/- 5.1 kg/m2. At one year
      of surgery, 85.5% patients achieved > 50%EWL. The highest mean %EWL was found in
      class 1 (66.19%), followed by class 2 (56.73%) and class 3 (46.59%) at the sixth
      month follow-up. At the seventh year, %EWLs were 85.11% (class 1), 76.69% (class
      2), and 62.98% (class 3) and the mean BMIs were 25.13 +/- 3.09 kg/m2 (class 1),
      26.86 +/- 2.12 kg/m2 (class 2), and 31.07 +/- 3.39 kg/m2 (class 3) and were
      significantly different (p < 0.05). At the last follow-up, though, the males
      showed slight weight regain; however, there were no statistical differences
      between the genders (p = 0.065). CONCLUSION: Outcome from LSG was better in
      patients with BMI < 40 kg/m2 compared to the patients with BMI > 40 kg/m2.
      Remission of obesity-related comorbidities was observed with LSG in all groups
      and gender did not influence the outcome significantly.

PMID- 30238217
TI  - Advanced Age Is a Risk Factor for Complications Following Abdominal
      Panniculectomy.
AB  - BACKGROUND: Widespread adoption of bariatric surgery in the treatment of obesity
      has led to greater numbers of patients seeking panniculectomy, including aged
      patients, who represent a rapidly growing proportion of the U.S population.
      Although the quality of life and functional benefits of abdominal panniculectomy
      have been established, its safety in patients 65 years and older has not been
      evaluated. METHODS: The American College of Surgeons National Surgical Quality
      Improvements (ACS-NSQIP) database was used to identify patients undergoing
      panniculectomy between 2010 and 2015. Age 65 years and older was the risk factor
      of interest, and primary outcomes included 30-day wound complications, overall
      complications, reoperation, readmission, and mortality. Multivariate regression
      was performed to control for confounders. RESULTS: Review of the database
      identified 7030 patients who underwent abdominal panniculectomy. When stratified
      by age, 6455 (91.8%) of patients were younger than 65, and 575 (8.2%) were 65 or
      older. Multivariate regression analysis demonstrated that age over 65 was a
      significant independent risk factor for wound complications (OR = 1.81; 95% CI
      1.35-2.42; p < 0.001) and all complications (OR = 1.46; 95% CI 1.15-1.87; p =
      0.002). BMI, smoking, diabetes, and partial or total dependence were also
      identified as significant independent risk factors for wound and all
      complications. CONCLUSION: Our analysis demonstrates that advanced age is an
      independent risk factor for wound and overall complications following abdominal
      panniculectomy. These results highlight the importance of preoperative evaluation
      and optimization of modifiable preoperative risk factors as well as close
      postoperative follow-up for safe outcomes in patients 65 and older.

PMID- 30238218
TI  - Correlation Between Symptomatic Gastro-Esophageal Reflux Disease (GERD) and
      Erosive Esophagitis (EE) Post-vertical Sleeve Gastrectomy (VSG).
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become the preferred
      bariatric procedure in many countries. However, there is one shortcoming of LSG
      in the long-term follow-up and this is the onset of GERD and erosive esophagitis
      (EE). Current evidence of the effect of SG on GERD did not consolidate to a
      consensus. In this study, we objectively evaluate the incidence of EE 1 year post
      LSG with upper endoscopy (EGD) and try to identify the significant variables and
      possible underlying mechanisms of the EE post-LSG. METHODS: Over a period of 5
      years (2011-2016) at Singapore General Hospital, we retrospectively reviewed a
      prospectively collected database of a cohort of patients whom had LSG by a single
      surgeon who routinely performed EGD pre-operative and 1 year post-operative to
      assess EE and hiatal hernia. Patient's endoscopic findings and demographic and
      anthropometric data were analyzed. RESULTS: We identified a total of 97 obese
      patients who underwent LSG at our hospital by studied surgeon. Sixty-three
      patients (64.9% of original sample) were finally evaluated in the present study,
      40 (59.7%) of whom were female. The mean (range) age of patients was 38.2 (18-66)
      years, and mean BMI was 36.3 +/- 4.1 kg/m2. Median time to follow-up EGD was 13
      months (range, 12-15). Following LSG, there was a significant decrease in both
      BMI (42.1 +/- 1.2 vs. 29.9 +/- 1.0 kg/m2) and percentage excess weight loss of
      56.6 +/- 3.6%. The prevalence of EE on endoscopy increased from 9 (14.3%) to 28
      (44.4%) patients. Of which 15 (23.8%) were grade A, 11 (17.5%) were grade B, and
      2 (3.2%) were grade C. There was no correlation between GERD symptoms with EE;
      however, our study found a trend suggesting higher prevalence of EE with a sleeve
      diameter measuring > 2 cm wide (p = 0.069). CONCLUSION: Although LSG is effective
      in treating obesity and its metabolic syndromes, the prevalence of EE increased
      significantly 1 year after the surgery. Since we do not fully understand the long
      term impact of chronic esophagitis in post-sleeve population, we recommend follow
      up EGD assessment post-operatively and treat the esophagitis if present.

PMID- 30238220
TI  - Evaluation of the Probiotic Potential of Saccharomyces cerevisiae Strain (C41)
      Isolated from Tibicos by In Vitro Studies.
AB  - Artisanal fermented beverages have been associated with beneficial effects for a
      long time. In Mexico, there are a wide variety of artisanal fermented beverages
      such as Tepache, where the fermentation is initiated by the addition of grains of
      a polysaccharide-containing biofilm matrix formed by a symbiotic association of
      bacteria and yeasts known as "Tibicos." These microorganisms can be responsible
      for the beneficial effect associated with fermented beverages inoculated with
      Tibicos. The probiotic potential of microorganisms has been widely studied,
      mainly in lactic acid bacteria, while despite the wide distribution of yeasts,
      these have not been so studied. Therefore, the aim of this study was to evaluate
      in vitro the probiotic potential properties of a yeast isolated from Tibicos. For
      this, the yeast was identified by molecular techniques as Saccharomyces
      cerevisiae, which showed a good resistance to pH 2.0, bile salts and in vitro
      digestion. The results also showed a good ability to form cellular aggregates as
      a result of having a hydrophobic surface. In addition, it can be considered as
      safe since it does not show hemolytic activity and is sensitive to nystatin.
      Additionally, the yeast presented an excellent antioxidant capacity to reduce the
      DPPH radical. The S. cerevisiae strain C41 isolated from Tibicos was successfully
      compared by means of in vitro tests with the only recognized probiotic yeast, S.
      boulardii. These findings point Saccharomyces cerevisiae C41 as a potentially
      probiotic yeast; nevertheless, it is necessary to consider further in vitro and
      in vivo studies that establish the benefits that this yeast could provide.

PMID- 30238219
TI  - Growth performance, lipid metabolism, and health status of grass carp
      (Ctenopharyngodon idella) fed three different forms of sodium butyrate.
AB  - Sodium butyrate (SB) can be coated with fatty acid matrix. In this study, the
      effects of three SB forms, being zero-lipid-coated (SB-A), half-lipid-coated (SB
      B), and 2/3 lipid-coated (SB-C) (w/w), on growth, lipid metabolism, and health
      status of grass carp (Ctenopharyngodon idella) were investigated. The three forms
      of SB were added to a control diet to form three SB diets, Con., SB-A, SB-B, and
      SB-C, where the pure SB in each SB diet was kept at the same level (500 mg kg-1).
      A total of 216 C. idella (14.10 +/- 0.60 g/fish) were allotted into four groups
      (triplicate per group) and fed the four diets respectively for 56 days, and then
      fish were sampled and determined. Fish growth was not affected by any of the
      three forms of SB. Viscerosomatic index, intraperitoneal fat index, and crude
      lipid of hepatopancreas and muscle were significantly decreased and villus height
      of intestine and mRNA expression of MyD88 and TLR22 in hepatopancreas were
      significantly improved in SB diets compared with control (p < 0.05),
      respectively. MiSeq sequencing of the V3-V4 region of bacterial 16S rRNA gene
      revealed that SB increased the relative abundances of intestinal healthy
      bacteria, Fusobacteria and Bacteroides, and the abundances of Cetobacterium
      decreased in the SB-C group. In conclusion, the present results showed that three
      forms of SB, without affecting the growth of fish, respectively decreased lipid
      accumulation and probably have a beneficial effect on health of C. idella.

PMID- 30238221
TI  - Principal component analysis-based features generation combined with ellipse
      models-based classification criterion for a ventricular septal defect diagnosis
      system.
AB  - In this study, a simple and efficient diagnostic system, which adopts a novel
      methodology consisting of principal component analysis (PCA)-based feature
      generation and ellipse models-based classification criterion, is proposed for the
      diagnosis of a ventricular septal defect (VSD). The three stages corresponding to
      the diagnostic system implementation are summarized as follows. In stage 1, the
      heart sound is collected by 3M-3200 electronic stethoscope and is preprocessed
      using the wavelet decomposition. In stage 2, the PCA-based diagnostic features,
      [[Formula: see text]], are generated from time-frequency feature matrix
      ([Formula: see text]). In the matrix TFFM, the time domain features [Formula: see
      text] are firstly extracted from the time domain envelope [Formula: see text] for
      the filtered heart sound signal [Formula: see text], and frequency domain
      features, [Formula: see text], are subsequently extracted from a frequency domain
      envelope ([Formula: see text]) for each heart sound cycle automatically segmented
      via the short time modified Hilbert transform (STMHT). In stage 3, support vector
      machines-based classification boundary curves for the dataset [Formula: see text]
      are first generated, and least-squares-based ellipse models are subsequently
      built for the classification boundary curve. Finally, based on the ellipse
      models, the classification criterion is defined for the diagnosis of VSD sounds.
      The proposed diagnostic system is validated by sounds from the internet and by
      sounds from clinical heart diseases. Moreover, comparative analysis to validate
      the usefulness of the proposed diagnostic system, mitral regurgitation and aortic
      stenosis sounds are used as examples for detection. As a result, the higher
      classification accuracy, which is achieved by this study compared to the other
      methods, is [Formula: see text], [Formula: see text], [Formula: see text] and
      [Formula: see text] for diagnosing small VSD, moderate VSD, large VSD and normal
      sounds, respectively.

PMID- 30238222
TI  - Defining sarcopenia in terms of skeletal health.
AB  - : Among several sarcopenic indices, height-adjusted appendicular lean mass (ALM)
      in men and BMI-adjusted ALM in women are associated with fragility fracture.
      Handgrip strength is the risk factor for fragility fracture. PURPOSE: Various
      sarcopenia definitions and cutoff points result in mixed skeletal health results.
      Here, we aimed to determine a suitable definition and elucidate the cutoff values
      of sarcopenic indices for identifying fracture risk in a community-dwelling
      Korean cohort. METHODS: In an Ansung cohort study (2009-2010), we included 1201
      men aged > 50 years and 1627 postmenopausal women with a median age of 64 years.
      Body composition and bone mineral density were derived on dual-energy X-ray
      absorptiometry. Grip strength was measured using a hand dynamometer. Fragility
      fractures included the history of osteoporotic fractures using self-reported
      questionnaires. RESULTS: Among appendicular lean mass (ALM)/body mass index
      (BMI), ALM/height2, and ALM/weight, ALM/height2 for men and ALM/BMI for women
      significantly predicted fragility fractures. On receiver operating characteristic
      curve analysis, the cutoff values of ALM/height2 in men and ALM/BMI in women were
      7.69 kg/m2, and 0.57, respectively. The optimal grip strength values were 31 kg
      in men and 19 kg in women. The odds ratios of low ALM/height2 (95% confidence
      interval) and weak grip strength for fragility fracture were 1.95 (1.03-3.68) and
      2.05 (1.01-4.18), respectively, in men after covariate adjustment. The
      combination of low ALM/height2 and weak grip strength increased fragility
      fractures 2.16-fold in men. Only the combination of low ALM/BMI and grip strength
      increased the fracture risk by 1.76-fold in women. CONCLUSIONS: In men, low
      ALM/height2 or grip strength played a role in fragility fractures. In women, only
      the combination of low ALM/BMI and grip strength had discriminatory power for
      fragility fractures.

PMID- 30238223
TI  - Correction to: Preclinical Development of Cell-Based Products: a European
      Regulatory Science Perspective.
AB  - The article [Preclinical Development of Cell-Based Products: a European
      Regulatory Science Perspective], written by [James W. McBlane, Parvinder Phul,
      and Michaela Sharpe], was originally published electronically on the publisher's
      internet portal (currently SpringerLink).

PMID- 30238224
TI  - Genome-wide identification of WRKY family genes and their response to abiotic
      stresses in tea plant (Camellia sinensis).
AB  - The WRKY transcription factors (TFs) family is one of the largest TF families in
      plants and plays a central role in diverse regulation and multiple stress
      responses. However, the systematical analysis of the WRKY gene family in tea
      plant (Camellia sinensis) based on genomic data has been lacking. The primary
      objective of this study was to set a systematic analysis of the WRKY gene family
      based on genomic data in tea plant and analyze their expression profiles under
      various abiotic stresses. We searched the tea plant genome using the consensus
      model of the WRKY domain (PF03106) and then used these search results to identify
      all the WRKY family members by SMART and the CDD program. Analyze their
      phylogeny, classification, structure, conserved motifs, Cis-elements, interactors
      and expression profiles. 56 putative WRKY genes were identified from the tea
      plant genome and divided into three main groups (I-III) and five subgroups (IIa
      IIe) according to the WRKY domains and the zinc-finger structure. The gene
      structure and conserved motifs of the CsWRKY genes were also characterized and
      were consistent with the classification results. Annotation analysis showed that
      34 CsWRKY genes may be involved in stress responses. Promoter analysis implied
      that CsWRKY genes, except for CsWRKY55, possessed at least one abiotic stress
      response cis-element. Expression profiles of CsWRKY genes in different tissues
      were analyzed with RNA-seq data. The results showed that 56 CsWRKY genes had
      differential expression in their transcript abundance. The expression profiles
      also showed that many identified CsWRKY genes were possibly involved in the
      response to cold, drought, salt, or ABA treatment. Tea plant genome contains at
      least 56 WRKY genes. These results provide useful information for further
      exploring the function and regulatory mechanism of CsWRKY genes in the growth,
      development, and adaption to abiotic stresses in tea plant.

PMID- 30238225
TI  - Deciphering genome-wide WRKY gene family of Triticum aestivum L. and their
      functional role in response to Abiotic stress.
AB  - WRKY transcription factors (TFs) act in regulating plant growth and development
      as well as in response to different stress. Some earlier studies done by
      individual researchers reported different wheat WRKY TFs. Although, the recently
      released wheat genome has opened an avenue to investigate wheat WRKYs (TaWRKY)
      TFs. Prime objective of this study to performed genome-wide classifications of
      TaWRKYs and their functional annotation. The classification of 107 individual
      identified characterized sequences of TaWRKY (IICS-TaWRKY) and 160
      uncharacterized draft sequences of TaWRKY (UDS-TaWRKY), along with their gene
      structures and motifs analysis was performed. Along with comparative sequence
      analysis and microarray analysis was performed to mimic out TaWRKYs functions in
      response to different abiotic stresses, accompanied by in-vitro validation. The
      comparative phylogenetic analysis and estimation of Ka/Ks ratio with Triticum
      urartu, illustrate group based clasifications of TaWRKYs and evolutionary
      divergences. Furthermore, motif-based and protein-DNA interaction analysis of
      TaWRKYs helps to identify, their putative function in target DNA recognition
      sites. Subsequently, results of microarray and comparative sequence analysis
      provides the evidence of TaWRKYs involved in heat and/or drought stress. Further,
      in-vitro results validates that TaWRKY014, TaWRKY090 are found to participate in
      response of drought stress, whereas TaWRKY008, TaWRKY122, and WRKY45 are involved
      in response of heat and drought stress. These findings can be utilized in
      developing novel heat and drought-tolerant wheat cultivars using marker-assisted
      breeding and transgenic development.

PMID- 30238226
TI  - Effects of corn particle size on nutrient utilization in pigs evaluated under
      optimal and heat stress conditions.
AB  - The effects of corn particle size on nutrient digestibility and energy
      utilization in pigs were determined under optimal (experiment 1, 25 +/- 1 
      degrees C) or heat stress (experiment 2, 37 +/- 1  degrees C) conditions. In Exp.
      1 and 2, five experimental diets were tested using a 5 * 5 Latin square design
      involving five barrows (Landrace * Yorkshire * Duroc, average initial body weight
      of 30 +/- 1 kg and 45.0 +/- 1.8 kg, respectively, in individual metabolic cages).
      Dietary treatments were as follows: 200-, 300-, 400-, 600-, 800-MUm corn particle
      sizes obtained by mesh screens. Under optimal thermal conditions, digestibility
      of dry matter (DM) and crude fiber (CF) from 200-MUm diet was higher (P < 0.05)
      compared to that from the 300-MUm and 400-MUm diets. The digestibility of crude
      protein (CP) and ether extract (EE) was the highest (P < 0.05) at the 200-MUm
      particle size. The apparent total tract digestibility of energy was significantly
      higher (P < 0.05) on the 200-MUm diet. Under heat stress, digestibility of CF
      when corn was ground to 600 MUm was higher (P < 0.05) compared to 300 and 400
      MUm. Digestibility of NDF and ADF was the highest (P < 0.05) at 600-MUm corn
      particle size. In conclusion, grinding corn to 200-MUm corn particles had a
      positive effect on DM, CP, EE, and CF under optimal thermal condition, while the
      600-MUm corn particle size had positive effects on digestibility of CF, NDF, and
      ADF than 200-MUm corn particle size under heat stress.

PMID- 30238228
TI  - Clinical Impact of 5 Years of Liraglutide Treatment on Cardiovascular Risk
      Factors in Patients with Type 2 Diabetes Mellitus in a Real-Life Setting in
      Italy: An Observational Study.
AB  - INTRODUCTION: Based on existing data regarding the durability of liraglutide in
      type 2 diabetes, this study aimed to assess its long-term effectiveness at 5
      years and its overall impact on cardiovascular (CV) risk. METHODS: This was a
      multicenter retrospective observational study. Liraglutide was used under routine
      clinical practice conditions. Changes from baseline to 60 months in HbA1c,
      fasting plasma glucose (FPG), body weight, blood pressure, and lipid profile were
      assessed. United Kingdom Prospective Diabetes Study (UKPDS) scores were
      calculated at baseline and after 60 months to assess changes in the estimated 5-
      and 10-year risk for fatal and nonfatal coronary heart disease (CHD) and fatal
      and nonfatal stroke. RESULTS: Overall, 103 patients (age 59.0 +/- 7.9 years,
      diabetes duration 10.4 +/- 6.8 years) were involved in the study. After 60
      months, HbA1c levels were reduced by - 1.0 +/- 1.2%, FPG levels by - 24.5 +/-
      43.4 mg/dl, body weight by - 5.3 +/- 6.4 kg, systolic blood pressure by - 6.5 +/-
      18.5 mmHg, diastolic blood pressure by - 3.6 +/- 11.8 mmHg, and total cholesterol
      by - 16.9 +/- 37.4 mg/dl. The proportion of patients achieving HbA1c levels  of <
      7% increased from 12.7% to 39.8% (p = 0.02). Based on the UKPDS scores,
      statistically significant reductions in the 5- and 10-year risk of nonfatal CHD
      and fatal CHD were found, with no change in the 5- and 10-year risk of fatal and
      nonfatal stroke. CONCLUSION: In patients prolonging treatment with liraglutide
      for 5 years, the benefits in relation to metabolic control and CV risk factors
      are maintained. The UKPDS risk scores suggest that liraglutide is associated with
      a reduced CHD risk, but not with a reduced stroke risk.

PMID- 30238227
TI  - Dexmedetomidine in prevention and treatment of postoperative and intensive care
      unit delirium: a systematic review and meta-analysis.
AB  - BACKGROUND: To determine the preventive and therapeutic effect of dexmedetomidine
      on intensive care unit (ICU) delirium. METHODS: The literature search using
      PubMed and the Cochrane Central Register of Controlled Trials was performed
      (August 1, 2018) to detect all randomized controlled trials (RCTs) of adult ICU
      patients receiving dexmedetomidine. Articles were included if they assessed the
      influence of dexmedetomidine compared to a sedative agent on incidence of ICU
      delirium or treatment of this syndrome. Accordingly, relevant articles were
      allocated to the following two groups: (1) articles that assessed the delirium
      incidence (incidence comparison) or articles that assessed the treatment of
      delirium (treatment comparison). Incidence of delirium and delirium resolution
      were the primary outcomes. We combined treatment effects comparing
      dexmedetomidine versus (1) placebo, (2) standard sedatives, and (3) opioids in
      random-effects meta-analyses. Risk of bias for each included RCT was assessed
      following Cochrane standards. RESULTS: The literature search resulted in 28
      articles (25 articles/4975 patients for the incidence comparison and three
      articles/166 patients for the treatment comparison). In the incidence comparison,
      heterogeneity was present in different subgroups. Administration of
      dexmedetomidine was associated with significantly lower overall incidence of
      delirium when compared to placebo (RR 0.52; 95% CI 0.39-0.70; I2 = 37%), standard
      sedatives (RR 0.63; 95% CI 0.46-0.86; I2 = 69%), as well as to opioids (RR 0.61;
      95% CI 0.44-0.83; I2 = 0%). Use of dexmedetomidine significantly increased the
      risks of bradycardia and hypotension. Limited data were available on circulatory
      insufficiency and mortality. In the treatment comparison, the comparison drugs in
      the three RCTs were placebo, midazolam, and haloperidol. The resolution of
      delirium was measured differently in each study. Two out of the three studies
      indicated clear favorable effects for dexmedetomidine (i.e., compared to placebo
      and midazolam). The study comparing dexmedetomidine with haloperidol was a pilot
      study (n = 20) with high variability in the results. CONCLUSION: Findings suggest
      that dexmedetomidine reduces incidence and duration of ICU delirium. Furthermore,
      our systematic searches show that there is limited evidence if a delirium shall
      be treated with dexmedetomidine.

PMID- 30238229
TI  - Using generalized additive models to investigate factors influencing
      cyanobacterial abundance through phycocyanin fluorescence in East Lake, China.
AB  - East Lake is a shallow lake (in Wuhan, China) where cyanobacteria blooms occurred
      frequently from 1970 to 1985. During the study period, all Carlson trophic state
      index values were > 50, indicating that East Lake is in a eutrophic state. In
      this study, phycocyanin concentrations were measured through phycocyanin
      fluorometry for rapid assessment of cyanobacterial abundance. The smoothing
      splines of the optimal generalized additive model (GAM) indicated that Secchi
      depth (SD), total phosphorus (TP) and dissolved oxygen (DO) concentrations,
      electrical conductivity (EC), chemical oxygen demand (COD), and ratios of total
      nitrogen (TN) to TP (TN:TP) were the main environmental factors in a moderate
      nonlinear relationship with cyanobacterial phycocyanin concentrations in East
      Lake. The shape of the GAM smoother can be used to quantify the relationship
      between a response variable and an explanatory variable in the scatterplot.
      Phycocyanin concentrations were sharply and negatively related to both SD and EC
      when the SD was 20-80 cm and EC was > 270 mg/L. Phycocyanin concentrations
      increased with concentrations of TP, DO, and COD. Phycocyanin concentrations
      increased sharply with TP concentrations when TP concentrations were > 0.10 mg/L
      and approached to a constant when DO concentrations were > 8.20 mg/L.
      Approximately, 85% of the phycocyanin concentrations were negatively correlated
      with TN:TP of < 26. In summary, organic compounds and TP were inferred to the key
      factors limiting the potential growth of cyanobacteria in East Lake. These change
      points/thresholds of smoothing splines of aforementioned variables may serve as a
      framework for managing the cyanobacterial growth.

PMID- 30238231
TI  - Antimicrobial activities of saponins from Melanthera elliptica and their
      synergistic effects with antibiotics against pathogenic phenotypes.
AB  - BACKGROUND: Resistance of bacteria and fungi to antibiotics is one of the biggest
      problems that faces public health. The present work was designated to evaluate
      the antimicrobial activities of saponins from Melanthera elliptica and their
      synergistic effects with standard antibiotics against pathogenic phenotypes. The
      plant extract was prepared by maceration in methanol. The methanol extract was
      partitioned into ethyl acetate and n-butanol extracts. Column chromatography of
      the n-butanol extract followed by purification of different fractions led to the
      isolation of four saponins. Their structures were elucidated on the basis of
      spectra analysis, and by comparison with those from the literature. The
      antimicrobial activities of the extracts/compounds alone and their combinations
      with tetracycline and fluconazole were evaluated using the broth microdilution
      method through the determination of minimum inhibitory concentration (MIC) and
      minimum microbicidal concentration. RESULTS: Four compounds: 3-O-beta-D
      glucuronopyranosyl-oleanolic acid (1), 3-O-beta-D-glucuronopyranosyloleanolic
      acid 28-O-beta-D-glucopyranosyl ester (2), 3-O-beta-D-glucopyranosyl(1 -> 2)-beta
      D-glucuronopyranosyl oleanolic acid (3) and 3-O-beta-D-glucopyranosyl(1 -> 2)
      beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester (4)
      were isolated. Compounds 1, 2 and 3 showed the largest antibacterial activities
      (MIC = 8-128 MUg/mL) whereas compound 4 displayed the highest antifungal
      activities (MIC = 8-16 MUg/mL). The antibacterial activities of compounds 1 and 2
      (MIC = 16-32 MUg/mL) against multi-drug-resistant Escherichia coli S2 (1) and
      Shigella flexneri SDINT are equal to those of vancomycin (MIC = 16-32 MUg/mL)
      used as reference antibiotic. CONCLUSIONS: The present study showed significant
      antimicrobial activity of compounds 1, 2, 3 and 4 against the tested
      microorganisms. The saponins act in synergy with the tested standard antibiotics.
      This synergy could lead to new options for the treatment of infectious diseases
      and emerging drug resistance.

PMID- 30238232
TI  - [Staffing levels and patient-related outcomes : Systematic literature review on
      international evidence].
AB  - The objective of this study was to systematically review the international
      literature with respect to significant links between staffing levels or
      qualification on the one hand and patient-related outcomes on the other. Of the
      initial 7778 abstracts identified by means of a complex search strand in PubMed
      and CINAHL, 51 could finally be included in a qualitative synthesis. A total of
      nine different patient-related outcome categories with significant associations
      on an at least ordinally scaled level were distinguished. None of the studies
      included had a (quasi-)experimental research design. Despite, in some instances,
      high numbers of cases at multiple sites and efforts to control obvious
      confounding variables by regression analysis, no evidence-based conclusions for
      health policy or clinical practice can be drawn from the available observational
      studies. There is therefore a considerable need for prospective randomized or at
      least quasi-experimental studies also as accompanying research on novel models of
      financing.

PMID- 30238230
TI  - A changing paradigm: management and treatment of the HCV/HIV-co-infected patient.
AB  - Hepatitis C virus (HCV) treatment in HIV/HCV co-infected individuals has renewed
      relevance given the ongoing opioid crisis and rise of new HIV and HCV infections
      associated with injection drug use. Patients co-infected with HIV and HCV
      demonstrate increased rates of hepatic fibrosis, progression to liver failure,
      and liver-related mortality. HIV co-infection does not impact outcomes of current
      HCV treatments, and patients should be treated the same as HCV mono-infected
      persons, though attention to drug:drug interactions is required. In this review,
      we discuss the mechanisms mediating injury to the liver in HIV mono-infection and
      HIV/HCV co-infection, and present the landmark trials of HCV treatment in HIV
      infected individuals.

PMID- 30238233
TI  - [Participation after stroke: the influence of depression in outpatient
      neurological rehabilitation].
AB  - BACKGROUND: Depressiveness is a known and common problem after stroke, which puts
      a great burden on those affected. The main goal for stroke rehabilitation is to
      achieve the maximum possible self-determination and participation in the
      community. This research study examined how depressive symptoms influence the
      course of participation in outpatient neurological rehabilitation. METHODS:
      Stroke rehabilitants from 17 German outpatient neurological rehabilitation
      centers were interviewed in a multicentric observational study. Within the
      current work, data on participation and depressive symptoms recorded at the
      beginning and at the end of rehabilitation by self-assessment questionnaires,
      were evaluated. RESULTS: Data of 342 rehabilitants were considered. Results of a
      multinomial logistic regression analysis indicated that the depression value at
      the end of rehabilitation, in particular, proved to be a good predictor for the
      improvement in participation. The lower the depressiveness, the more likely an
      improvement in participation. At the beginning of the rehabilitation program
      there were no significant differences between mean depression scores of patients
      who improved and patients who deteriorated. DISCUSSION: A relationship between
      depressiveness and participation was shown. The treatment of depressive symptoms
      through timely administered psychotherapeutic and medicinal care and general
      activity promotion could influence the participation in a beneficial way.

PMID- 30238234
TI  - Sensitive neurotoxicity assessment of bisphenol A using double
      immunocytochemistry of DCX and MAP2.
AB  - Bisphenol A (BPA) is an environmental toxin widely used in manufacturing
      industries. Studies conducted on the neurotoxicity of BPA demonstrated that at
      excessive, high concentrations (>= 200 uM) adverse responses occurred which were
      not detectable using traditional toxicity tests at lower chemical quantities than
      200 uM. Thus, a method capable of effectively detecting neurotoxicity at low
      concentrations (<= 100 uM) was devised. Bisphenol A-mediated neurotoxicity was
      examined in primary cultured neurons using various methods, including Western
      blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      cytotoxicity and reactive oxygen species assays. These methods confirmed BPA
      induced toxicity at 200 MUM, but no marked effect was observed at concentrations
      below 200 MUM. However, when immunocytochemistry (ICC) was performed using a co
      immunofluorescence assay of doublecortin (DCX) and microtubule-associated protein
      2 (MAP2), BPA adversely affected neuronal maturation in neural progenitor cells
      at concentrations as low as 100 uM, at which the three traditional methods failed
      to detect any neurotoxic effect. Our DCX/MAP2 ICC findings indicate that low
      concentrations of BPA are toxic to developing neurons, and suggest that the
      devised double ICC technique might provide an effective means of assessing
      neurotoxic effects of environmental toxins at low concentrations.

PMID- 30238235
TI  - Interactive role of weight status and fat talk on body dissatisfaction: an
      observation of women friends.
AB  - PURPOSE: The current study examined the interactive role of weight status and fat
      talk on body dissatisfaction among women friends. METHOD: Sixty pairs of women
      friends completed a measure of body dissatisfaction and engaged in an observed
      fat talk interaction with their friend. RESULTS: Women's weight status was
      related to their own, but not their friend's, body dissatisfaction. Observed fat
      talk was significantly related to individuals' own and their friend's body
      dissatisfaction. A significant interaction effect showed that the association
      between fat talk and body dissatisfaction was minimal for women with higher
      weight status. In contrast, fat talk was associated with more body
      dissatisfaction for women with lower weight status. CONCLUSION: These findings
      suggest the importance of examining the conjoint effect of personal (e.g., weight
      status) and contextual (e.g., fat talk) factors on body image issues. LEVEL OF
      EVIDENCE: V, cross-sectional descriptive study.

PMID- 30238237
TI  - Combined reconstruction of the medial patellofemoral and medial patellotibial
      ligaments: outcomes and prognostic factors.
AB  - PURPOSE: To report outcomes after combined medial patellofemoral ligament (MPFL)
      and medial patellotibial ligament (MPTL) reconstruction and test associations
      between prognostic factors and clinical outcomes. It was hypothesised that
      combined MPFL and MPTL reconstruction would result in significant improvement in
      function, and that outcomes would be associated with age, sex, Beighton score,
      concomitant articular lesions, and preoperative function. METHODS: All combined
      reconstructions of MPFL and MPTL were reviewed. Inclusion criterion was minimum 2
      year follow-up. Exclusion criteria were age at surgery >= 35 years and
      concomitant osteotomies. Kujala, Tegner and Marx scores were completed
      prospectively. Patients were evaluated at a minimum 2-year follow-up.
      Associations between potential prognostic factors and Kujala and Tegner scores
      were tested using bivariate analyses followed by multivariate regression models.
      RESULTS: Of 22 patients (26 knees), 19 (23 knees) met inclusion criteria, and 16
      (20 knees) were available for follow-up. Mean age at surgery was 18 years (range
      14.5-23). Mean follow-up was 43 months (range 24-73). Postoperative Kujala score
      significantly improved compared to before surgery (86.4 +/- 12.5 vs. 54.9 +/-
      15.2, p < 0.01). Postoperative Tegner score was nonsignificantly higher compared
      to before surgery (4.8 +/- 2.4 vs. 4 +/- 3, p = ns) and lower compared to before
      first patella dislocation (4.8 +/- 2.4 vs. 5.9 +/- 1.2, p < 0.01). Postoperative
      Kujala score was associated with male sex (p = 0.02), with medial patellofemoral
      chondral lesions (p = 0.01) and with preoperative Kujala score (p = 0.05).
      Postoperative Tegner score was associated with male sex (p < 0.01), with
      preoperative Tegner level (p < 0.01), and with Beighton score (p < 0.01). Patella
      apprehension was recorded in two knees (10%) in two patients. CONCLUSION:
      Combined MPFL and MPTL reconstruction in young adults results in significant
      improvement in subjective knee function with minimal risks, although preinjury
      activity levels are not consistently restored. Associated factors of improved
      outcome include higher preoperative knee scores and activity levels, medial
      patellofemoral chondral lesions, decreased Beighton scores, and male sex. This
      supports the advisability of the procedure and can also assist in setting
      realistic goals for specific groups of patients. LEVEL OF EVIDENCE: Case series,
      Level IV.

PMID- 30238238
TI  - No clinical difference in 10-year outcomes between standard and minimal graft
      debridement techniques in patients undergoing anterior cruciate ligament
      reconstruction using autologous hamstrings: a randomized controlled trial.
AB  - PURPOSE: Delayed ligamentization following anterior cruciate ligament
      reconstruction (ACLR) may result in reduced graft stiffness and strength, and an
      increased risk of secondary re-tear. Remnant sparing ACLR may accelerate
      ligamentization and proprioceptive function, theoretically reducing re-injury
      risk. This study sought to investigate 10-year graft failure rates and patient
      perceived knee functioning in those undergoing ACLR with remnant preservation
      (RP), versus remnant debridement (RD). METHODS: A prospective RCT allocated 49
      patients to ACLR with a hamstrings autograft together with a RD (n = 25) or RP (n
      = 24) procedure, of which 86% were clinically evaluated at 10 years (22 RD, 22
      RP). A detailed chart review and patient phone consultation was undertaken with
      all patients at 10 years to evaluate the incidence (and timing) of subsequent re
      tear and/or contralateral ACL tear, as well as other knee injuries/surgeries, the
      patient's ability to perform full work/sport duties and their perceived knee
      function using a numerical rating scale (NRS). RESULTS: No significant
      differences existed between groups in descriptive variables. There were 2 graft
      ruptures (10.0%) in the RP group and 3 (13.6%) in the RD group, with an earlier
      mean time to graft failure in the RD group (RD 7.7 +/- 4.5 months, RP 49.5 +/-
      17.7 months), albeit the size of this sub-sample was too small for statistical
      comparison. There was a significantly higher number of patients requiring >= 1
      additional ipsilateral knee surgery in the RP group (RP = 10, RD = 4, p = 0.048).
      At 10 years, there were no significant group differences in the percentage of
      patients returning to unrestricted activity, with 16 (72.7%) and 15 (75.0%)
      patients in the RD and RP ACLR groups, respectively, unrestricted in work/sport
      duties. There were no significant group differences in the functional NRS
      ratings. CONCLUSIONS: No long term clinical benefit of RP ACLR could be
      determined by this study with similar re-tear incidence and perceived knee
      function. A statistically higher number of re-operations were observed in RP ACLR
      patients and, while re-tears were observed later after RP versus RD ACLR, the
      study was underpowered to detect statistical significance. LEVEL OF EVIDENCE:
      Level II (prospective randomized controlled trial).

PMID- 30238239
TI  - Early stage periarticular injection during total knee arthroplasty may provide a
      better postoperative pain relief than late-stage periarticular injection: a
      randomized-controlled trial.
AB  - PURPOSE: This study was performed to determine whether periarticular injection
      performed in the early stage of total knee arthroplasty (TKA) could provide a
      better postoperative pain relief than periarticular injection performed in the
      late stage of TKA. The hypothesis was based on the concept that analgesic
      intervention before the onset of noxious stimuli would be associated with less
      postoperative pain. METHODS: A total of 105 participants were randomly assigned
      to receive superficial injection just prior to arthrotomy (early stage
      periarticular injection group) or superficial injection after implanting the
      prosthesis (late-stage periarticular injection group) in patients undergoing
      unilateral TKA with 1:1 treatment allocation. In both groups, deep injection was
      performed according to the same schedule (just prior to implanting prosthesis).
      The solution consisted of 300 mg of ropivacaine, 8 mg of morphine, 40 mg of
      methylprednisolone, 50 mg of ketoprofen, and 0.3 mg of epinephrine mixed with
      normal saline to a final volume of 60 mL. All surgeries were managed under
      general anesthesia without any regional blocks. Registry-specified primary
      outcome was postoperative pain score at rest measured at the recovery room using
      a 100-mm visual analog scale (VAS). The VAS score was compared between two groups
      and assessed to reach the reported threshold values for the minimal clinically
      important difference (MCID) of 10 mm for the postoperative VAS score. RESULTS:
      The VAS score at the recovery room was significantly lower in the early stage
      periarticular injection group than the late-stage periarticular injection group
      (23 +/- 25 mm versus 39 +/- 34 mm, respectively; 95% confidence interval 4-28 mm;
      p = 0.0078). The mean difference in the primary outcome fulfilled the MCID value.
      CONCLUSIONS: Bringing forward the timing of periarticular injection may provide
      significant and clinically meaningful improvement in pain following TKA under
      general anesthesia. LEVEL OF EVIDENCE: I.

PMID- 30238240
TI  - Epitope determines efficacy of therapeutic anti-Tau antibodies in a functional
      assay with human Alzheimer Tau.
AB  - In Alzheimer's disease (AD) and other tauopathies, the cytosolic protein Tau
      misfolds and forms intracellular aggregates which accumulate within the brain
      leading to neurodegeneration. Clinical progression is tightly linked to the
      progressive spread of Tau pathology throughout the brain, and several lines of
      evidence suggest that Tau aggregates or "seeds" may propagate pathology by
      spreading from cell to cell in a "prion like" manner. Accordingly, blocking the
      spread of extracellular seeds with an antibody could be a viable therapeutic
      approach. However, as the structure of Tau seeds is unknown, it is only possible
      to rationally design therapeutic Tau antibodies by making a priori assumptions.
      To avoid this, we developed a robust and quantitative cell based assay and
      employed an unbiased screening approach to identify the antibody with the highest
      activity against human Tau seeds. The selected antibody (D), directed to the mid
      region of Tau (amino acids 235-250), potently blocked the seeding of human AD Tau
      and was also fully efficacious against seeds from progressive supranuclear palsy.
      When we compared this antibody with previously described reference antibodies, we
      were surprised to find that none of these antibodies showed comparable efficacy
      against human pathological seeds. Our data highlight the difficulty of predicting
      antibody accessible epitopes on pathological Tau seeds and question the potential
      efficacy of some of the Tau antibodies that are currently in clinical
      development.

PMID- 30238241
TI  - Coralloluteibacterium thermophilus sp. nov., A Gammaproteobacterium Isolated from
      an Oil Reservoir.
AB  - A Gram-negative, yellow-pigmented, aerobic bacterium, designated strain B51-30T,
      was isolated from oil-well production liquid in Baolige oilfield, China. The
      strain was able to grow at pH 6-10 (optimum at pH 7.5), in 0-6% (w/v) NaCl
      (optimum at 1%, w/v) at 15-55  degrees C (optimum at 45  degrees C). Cells of the
      isolate were non-motile and non-spore-forming rods. The major cellular fatty
      acids were iso-C15:0, iso-C11:0, iso-C11:0 3OH, iso-C17:1 omega9c, and iso-C17:0.
      Ubiquinone 8 was the predominant respiratory quinone. The major polar lipids
      consisted of phosphatidylethanolamine and diphosphatidylglycerol. The genomic DNA
      G+C content of the isolate was 70.6 mol%. Phylogenetic analysis based on 16S rRNA
      gene sequences revealed that strain B51-30T was most closely related to
      Coralloluteibacterium stylophorae KCTC 52167T (98.7% similarity). The two strains
      showed DNA-DNA relatedness values of 58.5%. Genotypic and phenotypic features
      indicate that strain B51-30T represents a novel species of the genus
      Coralloluteibacterium, for which the name Coralloluteibacterium thermophilus sp.
      nov. is proposed. The type strain is B51-30T (= CGMCC 1.13574T = KCTC 62780T).

PMID- 30238243
TI  - The Impact of Education and Prescribing Guidelines on Opioid Prescribing for
      Breast and Melanoma Procedures.
AB  - BACKGROUND: Excessive opioid prescribing is common in surgical oncology, with 72%
      of prescribed opioids going unused after curative-intent surgery. In this study,
      we sought to reduce opioid prescribing after breast and melanoma procedures by
      designing and implementing an intervention focused on education and prescribing
      guidelines, and then evaluating the impact of this intervention. METHODS: In this
      single-institution study, we designed and implemented an intervention targeting
      key factors identified in qualitative interviews. This included mandatory
      education for prescribers, evidence-based prescribing guidelines, and
      standardized patient instructions. After the intervention, interrupted time
      series analysis was used to compare the mean quantity of opioid prescribed before
      and after the intervention (July 2016-September 2017). We also evaluated the
      frequency of opioid prescription refills. RESULTS: During the study, 847 patients
      underwent breast or melanoma procedures and received an opioid prescription. For
      mastectomy or wide local excision for melanoma, the mean quantity of opioid
      prescribed immediately decreased by 37% after the intervention (p = 0.03),
      equivalent to 13 tablets of oxycodone 5 mg. For lumpectomy or breast biopsy, the
      mean quantity of opioid prescribed decreased by 42%, or 12 tablets of oxycodone 5
      mg (p = 0.07). Furthermore, opioid prescription refills did not significantly
      change for mastectomy/wide local excision (13% vs. 14%, p = 0.8), or
      lumpectomy/breast biopsy (4% vs. 5%, p = 0.7). CONCLUSION: Education and
      prescribing guidelines reduced opioid prescribing for breast and melanoma
      procedures without increasing the need for refills. This suggests further
      reductions in opioid prescribing may be possible, and provides rationale for
      implementing similar interventions for other procedures and practice settings.

PMID- 30238244
TI  - Imaging Surveillance After Definitive Treatment for Breast Cancer.

PMID- 30238245
TI  - ASO Author Reflections: Induced Bias Due to Crossover Within Randomized
      Controlled Trials in Surgical Oncology.

PMID- 30238242
TI  - Pluripotent Very Small Embryonic-Like Stem Cells in Adult Testes - An Alternate
      Premise to Explain Testicular Germ Cell Tumors.
AB  - Developmental exposure to endocrine disruptors has resulted in the increased
      incidence of infertility and testicular germ cell tumors (T2GCT) in young men
      residing in developed countries. Unlike T1GCT (infants and young children) and
      T3GCT (aged men), T2GCT arise from CIS/GCNIS that develops from pre-CIS. Pre-CIS
      represents undifferentiated, growth-arrested gonocytes that persist in fetal
      testes due to endocrine disruption. However, whether pre-CIS truly exist, do CIS
      develop into T2GCT, why no CIS in T1GCT/T3GCT, why germ cell tumors (GCT) also
      occur along midline at extra-gonadal sites, why T1GCT show partial erasure and
      T2GCT show complete erasure of genomic imprints are open questions that are
      awaiting answers. We propose that rather than pre-CIS, pluripotent, very small
      embryonic-like stem cells (VSELs) get affected by exposure to endocrine
      disruption. Since VSELs are developmentally equivalent to primordial germ cells
      (PGCs), T2GCT cells show complete erasure of genomic imprints and CIS represents
      growth-arrested clonally expanding stem/progenitor cells. PGCs/VSELs migrate
      along the midline to various organs and this explains why GCT occur along the
      midline, T1GCT show partial erasure of imprints as they develop from migrating
      PGCs. T3GCT possibly reflects effects of aging due to compromised differentiation
      and expansion of pre-meiotic spermatocytes. Absent spermatogenesis in pre
      pubertal and aged testes explains absence of CIS in T1GCT and T3GCT. Endocrine
      disruptors possibly alter epigenetic state of VSELs and thus rather than
      maintaining normal tissue homeostasis, VSELs undergo increased proliferation and
      compromised differentiation resulting in reduced sperm count, infertility and
      TGCT. This newly emerging understanding offers alternate premise to explain TGCT
      and warrants further exploration.

PMID- 30238246
TI  - The Memorial Sloan Kettering Cancer Center Nomogram is More Accurate than the
      2009 FIGO Staging System in the Prediction of Overall Survival in a German
      Endometrial Cancer Patient Cohort.
AB  - BACKGROUND: Despite the complexity of endometrial cancer (EC) tumor biology,
      treatment decisions are still mainly based on the post-surgical International
      Federation of Gynecology and Obstetrics (FIGO) stage. Prediction models
      considering more prognostic factors may represent a better risk assessment than
      FIGO stage alone. We tested the Memorial Sloan Kettering Cancer Center (MSKCC)
      nomogram for the prediction of overall survival (OS) in a German EC population.
      METHODS: Overall, 454 EC patients (322 type I and 132 type II) who received
      primary surgical treatment at our department between 1991 and 2011 were included
      in the analysis with a dataset of 68 covariates. Predicted OS was calculated
      using the online MSKCC nomogram and compared with the observed survival in our
      population. To estimate the discriminatory power, the concordance probabilities
      were calculated using the concordance probability estimate (CPE). Receiver
      operating characteristic curves were created and the area under the curve (AUC)
      values compared between predicted and actual OS. RESULTS: After a mean follow-up
      of 183 months, 211 patients were reported dead (47%). Mean OS for all stages was
      101 months (standard deviation 66.7 months). The 2009 FIGO system showed an AUC
      value of 0.6 and a CPE of 0.63, while the 3-year OS prediction of the MSKCC
      nomogram showed an AUC value of 0.8 and a CPE of 0.77. CONCLUSION: This external
      validation of the MSKCC nomogram showed better discrimination and calibration
      values than the conventional FIGO classification system. The nomogram was
      externally validated and can serve as a tool for better risk-adapted treatment
      decisions and patient stratification, e.g. in clinical trials.

PMID- 30238247
TI  - Should All Stage N3b Patients with Advanced Gastric Cancer Be Considered
      Equivalent? A 30-Year Single Center Study.
AB  - PURPOSE: To investigate the survival of stage N3b patients with advanced gastric
      cancer (AGC) after radical surgery and to evaluate the TNM staging of subgroups
      of stage N3b patients. METHODS: We reviewed the data of 222 stage N3b patients
      with AGC who underwent D2/D3 radical surgery. Depending on the number of
      metastatic lymph nodes (MLNs), we divided N3b patients into several groups and
      compared the survival differences among them. We found that survival of patients
      with 16-20 MLNs was better than that of patients with >= 21 MLNs. Therefore, we
      divided the N3b patients into two subgroups and defined patients with 16-21 MLNs
      as N3b1 and patients with >= 21 MLNs as N3b2. Then, we compared survival
      differences between the two groups and their subgroups. Patients who underwent
      palliative surgery served as the reference group. In addition, we selected stage
      IIIB, IIIC, and IV patients from the same database to properly re-classify the
      N3b subgroups in the TNM staging system. RESULTS: Survival differed significantly
      between the new N3b1and N3b2 groups and between the new N3b1 group and the
      palliative group. However, the survival of the new N3b2 group was similar to that
      of the palliative group. Comparisons of survival according to T staging revealed
      similarities between the following groups: (1) stages T2-3N3b1 and IIIB, (2)
      stages T4N3b1 and IIIC, and (3) stages T2-4N3b2 and IV. CONCLUSIONS: All stage
      N3b patients with AGC should not be considered equivalent. A significant
      difference in survival was observed between stage N3b1 and N3b2 patients after
      radical surgery, while the survival of stage N3b2 patients was similar to that of
      patients who undergo palliative surgery. We recommend re-classifying stage T2
      3N3b1 as TNM stage IIIB, stage T4N3b1 as stage IIIC, and T2-4N3b2 as stage IV.

PMID- 30238248
TI  - A Thousand and One Laparoscopic Heller Myotomies for Esophageal Achalasia: a 25
      Year Experience at a Single Tertiary Center.
AB  - BACKGROUND: The aim of this study was to assess the long-term outcome of
      laparoscopic Heller-Dor (LHD) myotomy to treat achalasia at a single high-volume
      institution in the past 25 years. METHODS: Patients undergoing LHD from 1992 to
      2017 were prospectively registered in a dedicated database. Those who had already
      undergone surgical or endoscopic myotomy were ruled out. Symptoms were collected
      and scored using a detailed questionnaire; barium swallow, endoscopy, and
      manometry were performed before and after surgery; and 24-h pH monitoring was
      done 6 months after LHD. RESULTS: One thousand one patients underwent LHD (M:F =
      536:465), performed by six staff surgeons. The surgical procedure was completed
      laparoscopically in all but 8 patients (0.8%). At a median of follow-up of 62
      months, the outcome was positive in 896 patients (89.5%), and the probability of
      being cured from symptoms at 20 years exceeded 80%. Among the patients who had
      previously received other treatments, there were 25/182 failures (13.7%), while
      the failures in the primary treatment group were 80/819 (9.8%) (p = 0.19). All
      105 patients whose LHD failed subsequently underwent endoscopic pneumatic
      dilations with an overall success rate of 98.4%. At univariate analysis, the
      manometric pattern (p < 0.001), the presence of a sigmoid megaesophagus (p =
      0.03), and chest pain (p < 0.001) were the factors that predicted a poor outcome.
      At multivariate analysis, all three factors were independently associated with a
      poor outcome. Post-operative 24-h pH monitoring was abnormal in 55/615 patients
      (9.1%). CONCLUSIONS: LHD can durably relieve achalasia symptoms in more than 80%
      of patients. The pre-operative manometric pattern, the presence of a sigmoid
      esophagus, and chest pain represent the strongest predictors of outcome.

PMID- 30238249
TI  - Reply to Garcia-Tabar et al.: Quality control of open-circuit respirometry: real
      time, laboratory-based systems. Let us spread "good practice".
AB  - PURPOSE: This article is in response to the Letter of Garcia-Tabar et al. [Eur J
      Appl Physiol (in press), 2018] relating to the issue of post-test sensor
      calibration 'verification'. This issue is poorly addressed in contemporary
      patient-related position statements on cardiopulmonary exercise testing (CPET).
      METHODS: Post-test sensor calibration verification approaches were compared.
      RESULT: The potential impact on data quality of changing sensor calibration
      during the course of an exercise test was described. CONCLUSION: It is
      recommended that post-test sensor calibration verification be incorporated into
      existing CPET 'best practice'.

PMID- 30238250
TI  - Quality control of open-circuit respirometry: real-time, laboratory-based
      systems. Let's spread "good practice".

PMID- 30238251
TI  - beta-Adrenergic receptor blockade does not modify non-thermal sweating during
      static exercise and following muscle ischemia in habitually trained individuals.
AB  - PURPOSE: This study investigated the influence of beta-adrenergic receptor
      blockade on sweating during bilateral static knee extension (KE) and lateral
      isometric handgrip (IH) exercises followed by post-exercise muscle ischemia
      (PEMI) in habitually trained individuals. METHOD: Ten habitually trained men
      (maximum oxygen uptake, 57.1 +/- 3.4 ml kg-1 min-1) were mildly heated by
      increasing their skin temperature, and bilateral KE or lateral IH exercises at an
      intensity of 60% maximum voluntary contraction were subsequently performed for 1
      min, followed by PEMI to stimulate muscle metaboreceptors for 2 min. Sweat rates
      were measured on the bilateral forearms (KE) or thighs (IH) transdermally
      administered with 1% propranolol (propranolol, a non-selective beta-adrenergic
      receptor inhibitor) or saline (control) via iontophoresis. RESULTS: Relative to
      the pre-exercise baseline values, IH exercise (P = 0.038) followed by PEMI (P =
      0.041) similarly increased sweat rates on the thighs at both control and
      propranolol sites (baseline, 0.05 +/- 0.04 vs. 0.05 +/- 0.04; IH, 0.14 +/- 0.12
      vs. 0.15 +/- 0.14; PEMI, 0.14 +/- 0.16 vs. 0.14 +/- 0.16 mg cm-2 min-1). KE
      increased sweat rates on the forearms (P = 0.001) at both control and propranolol
      sites similarly (baseline, 0.02 +/- 0.03 vs. 0.02 +/- 0.03; KE, 0.21 +/- 0.19 vs.
      0.20 +/- 0.18), whereas PEMI did not significantly induce sweating at these sites
      (P = 0.260) (0.09 +/- 0.12 and 0.10 +/- 0.12 mg cm-2 min-1, respectively).
      CONCLUSION: These results suggest that non-thermal drives induced by static
      exercise and PEMI do not elicit beta-adrenergic sweating in habitually trained
      individuals even when the non-thermal drives are originated from leg(s) under the
      conditions in the present study.

PMID- 30238252
TI  - Local and nonlocal counterparts of global descriptors: the cases of chemical
      softness and hardness.
AB  - A new strategy, recently reported by us to develop local and linear (nonlocal)
      counterparts of global response functions, is applied to study the local behavior
      of the global softness and hardness reactivity descriptors. Within this approach
      a local counterpart is designed to identify the most important molecular
      fragments for a given chemical response. The local counterpart of the global
      softness obtained through our methodology corresponds to the well-known
      definition of local softness and, in agreement with what standard conceptual
      chemical reactivity in density functional theory dictates, it simply reveals the
      softest sites in a molecule. For the case of the local hardness, we obtain two
      expressions that lead to different information regarding the values of the
      hardness at the different sites within a chemical species. The performance of
      these two proposal were tested by comparing their corresponding atom-condensed
      values to experimentally observed reactivity trends for electrophilic attack on
      benzene and ethene derivatives.

PMID- 30238255
TI  - Genetic mapping of Stb19, a new resistance gene to Zymoseptoria tritici in wheat.
AB  - KEY MESSAGE: A new and dominant R gene Stb19 is identified from a soft wheat
      cultivar 'Lorikeet' and was mapped on the distal region of chromosome 1DS. Two
      tightly linked KASP markers were also discovered and validated for molecular
      assisted breeding programs. A new R gene, designated as Stb19, provides
      resistance to Zymoseptoria tritici in wheat. This new dominant gene resides on
      the short arm of chromosome 1D, exhibiting complete resistance to three Z.
      tritici isolates, WAI332, WAI251, and WAI161, at the seedling stage. A genetic
      linkage map, based on an F2:3 population of 'Lorikeet' and 'Summit,' found the
      Stb19 gene at a 9.3 cM region on 1DS, closely linked with two Kompetitive Allele
      Specific PCR markers, snp_4909967 and snp_1218021. Further, the two markers were
      tested and validated in another F2:3 population and 266 different wheat
      accessions, which gave over 95% accuracy of resistance/susceptibility prediction.
      Combined with the physical location of the identified SNPs and the previous
      evidence of gene order on chromosome 1DS (centromere-Sr45-Sr33-Lr21-telomere),
      Stb19 is proposed to be located between Sr33 and Lr21. Thus, the newly discovered
      Stb19 along with the KASP markers represents an increase in genetic resources
      available for wheat breeding resistance to Z. tritici.

PMID- 30238254
TI  - Fine mapping and candidate gene identification of the genic male-sterile gene ms3
      in cabbage 51S.
AB  - KEY MESSAGE: The ms3 gene responsible for a male-sterile phenotype in cabbage was
      mapped to a 187.4-kb genomic fragment. The gene BoTPD1, a homolog of Arabidopsis
      TPD1, was identified as a strong candidate gene. Cabbage 51S is a spontaneous
      male-sterile mutant. Phenotypic investigation revealed defects in anther cell
      differentiation, with failure to form the tapetum layer and complete abortion of
      microsporocytes before the tetrad stage. Genetic analysis indicated that this
      male sterility was controlled by a single recessive gene, ms3. Using an F2
      population, we mapped ms3 to a 187.4-kb interval. BoTPD1 was identified as a
      candidate from this interval. Sequence analysis revealed an intronic 182-bp
      insertion in 51S that interrupted the conserved motif at the 5' splicing site of
      the third intron, possibly resulting in a truncated transcript. Analyses of
      BoTPD1 homologous proteins revealed evolutionarily conserved roles in anther cell
      fate determination during reproductive development. RT-PCR showed that BoTPD1 was
      expressed in various tissues, excluding the root, and high expression levels were
      detected in anthers and buds. A BoTPD1-specific marker based on the 182-bp
      insertion cosegregated with male sterility and can be used for marker-assisted
      selection.

PMID- 30238256
TI  - Enhancement of visible-light photocatalytic activities of BiVO4 coupled with g
      C3N4 prepared using different precursors.
AB  - Graphitic-like carbon nitride (g-C3N4) photocatalyst was synthesized by a facile
      chemical pyrolysis method, which was built on the self-condensation of different
      precursors to generate g-C3N4, e.g., melamine, urea, and thiocarbamide. And the
      different precursors produced a great influence on the photocatalytic activities
      of g-C3N4. Heterojunctions of g-C3N4 and BiVO4 were synthesized using a facile
      solvent evaporation method. The formation of BiVO4/g-C3N4 composites were
      confirmed by XRD, FT-IR, SEM, XPS, and UV-Vis DRS. The photocatalytic activities
      for RhB degradation were evaluated under visible-light irradiation. The
      photocatalytic activity of g-C3N4 prepared by urea was higher than that of g-C3N4
      prepared by melamine and thiocarbamide, which was attributed to its favorable
      dispersibility, larger specific surface area, and higher oxidation capacity. The
      heterojunction composites exhibited higher photocatalytic activity than pure g
      C3N4 or BiVO4. The results showed obvious removal efficiency for RhB, and the
      optimal sample with a BiVO4 content of 10% exhibited higher efficiency than pure
      g-C3N4 and BiVO4, and 10 wt%BiVO4/CN-U showed the highest photocatalytic
      activity. The enhanced photocatalytic activity of BiVO4/g-C3N4 composite can be
      attributed to the intimate coupling between the two host substrates, resulting in
      an efficient charge separation.

PMID- 30238257
TI  - Assessment of anticytotoxic effect of lichen Cladonia foliacae extract on Allium
      cepa root tips.
AB  - The aim of this study is to investigate the protective effect of lichen Cladonia
      foliacae (Huds.) (CF) on hydrogen peroxide (H2O2)-induced toxicity through cell
      death, chromosome aberrations, mitotic index, oxidative stress parameters, and
      DNA damage in a Allium cepa root meristematic cells. Any chemical was not given
      for control group. Two doses of H2O2 (3 and 7%) were given to the roots for 1 h
      and the root tips were treated with CF water extract (50 and 100 MUL) with
      increasing times for treatment groups. The roots were taken from control and
      treatment groups, and mitotic index, cell death, and chromosome aberrations were
      performed by light microscope. Changing antioxidant capacity of roots was
      revealed by FRAP and TEAC assay. Also, DNA damage was measured by comet assay and
      RAPD-PCR technique. Chromosome aberration values were obtained with increasing
      concentrations with longer treatment times, such as chromosome bridge, vagrant,
      and polyploidy in both groups. Increasing exposure doses of H2O2 caused
      decreasing mitotic index values at 72 h. TEAC and FRAP assay demonstrated that
      roots' capacity of antioxidant was altered by increasing concentrations of H2O2.
      The tail DNA% and tail length significantly increased in all exposure times when
      compared to control group. Three and seven percent of H2O2 caused the genotoxic
      effect on genetic material at 72 h according to RAPD-PCR technique. Increasing
      the doses of H2O2 resulted in increased toxicity to all studied parameters of A.
      cepa, but CF extract altered all changing parameters of A. cepa root cell. The
      H2O2 tested in this study have cytotoxic and mutagenic potential, but extract of
      CF was protective against H2O2 caused toxicological changes. But, it did not
      protect completely in the A. cepa root meristematic cells.

PMID- 30238258
TI  - Sustainable survival under climatic extremes: linking flood risk mitigation and
      coping with flood damages in rural Pakistan.
AB  - Various measures are adopted by flood-prone households for the mitigation of
      flood risk along with various post-flood coping strategies. We analyze the role
      of various ex ante household-level flood mitigation strategies in influencing
      riverine flood damages. The study also presents an account on the linkages of
      various ex post coping strategies and flood damages experienced in a flood event
      in Pakistan. For achieving a uniform flood damage indicator, polychoric principle
      component analysis (PCA) is employed to construct a composite flood damage index
      considering various aspects of economic, social, and psychological impacts of a
      flood event. The adjusted flood damage index is regressed on various
      socioeconomic features and ex ante mitigation actions to know their effect on the
      former. Results indicate that distance from river, elevating house, and pre
      shifting investigating about flooding problem help in significantly reducing the
      overall flood damages. Likewise, group-based actions like voting political
      candidates based on their flood-control promises, organizing grass-root group
      meetings, and raising voices through memos/petitions are found to significantly
      reduce flood-related damages while leaving house premises before flooding is
      found to increase the overall flood damage. Post-flood coping strategies comprise
      of social and financial support along with some livelihood diversification and
      disinvestment strategies such as selling livestock, jewelry, and withdrawing
      children from schools. Borrowing money, reducing food consumption, and
      agricultural diversification are more prevalent strategies among low and medium
      damage groups while consuming savings is more conspicuous among high damage
      group. The study concludes with the emphasis on policy interventions for
      effective early warning, location-specific flood intensity information, and
      proper streamlining of planning process and compensation system.

PMID- 30238253
TI  - Regulation of carbamoylphosphate synthesis in Escherichia coli: an amazing
      metabolite at the crossroad of arginine and pyrimidine biosynthesis.
AB  - In all organisms, carbamoylphosphate (CP) is a precursor common to the synthesis
      of arginine and pyrimidines. In Escherichia coli and most other Gram-negative
      bacteria, CP is produced by a single enzyme, carbamoylphosphate synthase
      (CPSase), encoded by the carAB operon. This particular situation poses a question
      of basic physiological interest: what are the metabolic controls coordinating the
      synthesis and distribution of this high-energy substance in view of the needs of
      both pathways? The study of the mechanisms has revealed unexpected moonlighting
      gene regulatory activities of enzymes and functional links between mechanisms as
      diverse as gene regulation and site-specific DNA recombination. At the level of
      enzyme production, various regulatory mechanisms were found to cooperate in a
      particularly intricate transcriptional control of a pair of tandem promoters.
      Transcription initiation is modulated by an interplay of several allosteric DNA
      binding transcription factors using effector molecules from three different
      pathways (arginine, pyrimidines, purines), nucleoid-associated factors (NAPs),
      trigger enzymes (enzymes with a second unlinked gene regulatory function), DNA
      remodeling (bending and wrapping), UTP-dependent reiterative transcription
      initiation, and stringent control by the alarmone ppGpp. At the enzyme level,
      CPSase activity is tightly controlled by allosteric effectors originating from
      different pathways: an inhibitor (UMP) and two activators (ornithine and IMP)
      that antagonize the inhibitory effect of UMP. Furthermore, it is worth noticing
      that all reaction intermediates in the production of CP are extremely reactive
      and unstable, and protected by tunneling through a 96 A long internal channel.

PMID- 30238260
TI  - Optimization of techniques for the extinction and prevention of coal fires
      produced in final walls as a result of spontaneous combustion in the Cerrejon
      mine-Colombia.
AB  - The Cerrejon mine has identified fires in its coal production seams for a few
      years in its operation. Fires are produced as a result of spontaneous combustion
      phenomena. Coal spontaneous combustion is a phenomenon that occurs naturally
      during coal oxidation when exposed to atmospheric conditions, due to erosion
      processes, geological and mining practices. This phenomenon is a subject of great
      concern in the world's coal mines, as it causes environmental problems,
      generating emissions of polluting gases into the atmosphere and economic losses
      due to reserve consumption. In this work, we seek to optimize the prevention and
      extinction processes used by the company. In terms of prevention, the current
      state was evaluated and alternatives, such as diluted bitumen and brine
      (combustion inhibitor), cement/slaked lime, fine sand cement, and clinker/slaked
      lime were developed to avoid ignition. As far as extinction is concerned, an
      additional methodology for medium magnitude fires was determined, in order to
      improve extinction times through the use of cooling. It was determined that the
      bitumen/brine has better adhesion and durability properties in the coal seam.
      Extinction through reagent cooling is quicker, thus improving the backhoe's
      productivity and minimizing costs.

PMID- 30238259
TI  - Plasma metabonomics investigation reveals involvement of fatty acid oxidation in
      hematotoxicity in Chinese benzene-exposed workers with low white blood cell
      count.
AB  - Benzene is an environmental and occupational contaminant. Health hazards
      associated with occupational benzene exposure is a major public health problem in
      China. In this study, we analyzed metabolite profiles among plasma samples
      collected from benzene-exposed workers with low white blood cell count (BLWs) and
      healthy controls using high-performance liquid chromatography-time-of-flight mass
      spectrometry. To screen potential benzene hematotoxicity biomarkers and metabolic
      pathways, principal component analysis was used to examine metabolite profile
      changes in plasma samples. The alterations in fatty acid oxidation (FAO) pathway
      were consistent with our previous findings in a mouse model; hence, two key genes
      were selected and verified in WBC samples. A total of nine identified metabolites
      were significantly changed in BLWs, which were involved in glutathione
      metabolism, porphyrin metabolism, lipid metabolism pathway, and FAO metabolism.
      Furthermore, compared with healthy controls, the mRNA expressions of carnitine
      acyltransferase (CRAT) and ACADVL were significantly increased in BLWs.
      Particularly, WBC counts was negatively correlated with the expression of AVADVL
      in BLWs. These aberrant metabolites could act as potential biomarkers for benzene
      hematotoxicity. In addition, fatty acid oxidation pathway may play a critical
      role in the development of hematotoxicity caused by benzene.

PMID- 30238261
TI  - Towards visible-light photocatalysis for environmental applications: band-gap
      engineering versus photons absorption-a review.
AB  - A range of different studies has been performed in order to design and develop
      photocatalysts that work efficiently under visible (and near-infrared)
      irradiation as well as to improve photons absorption with improved reactor
      design. While there is consensus on the importance of photocatalysis for
      environmental applications and the necessity to utilized solar irradiation (or
      visible-light) as driving force for these processes, it is not yet clear how to
      get there. Discussion on the future steps towards visible-light photocatalysis
      for environmental application is of great interest to scientific and industrial
      communities and the present paper reviews and discusses the two main approaches,
      band-gap engineering for efficient solar-activated catalysts and reactor designs
      for improved photons absorption. Common misconceptions and drawbacks of each
      technology are also examined together with insights for future progress.

PMID- 30238262
TI  - Groundwater vulnerability assessment using the GALDIT model and the improved
      DRASTIC model: a case in Weibei Plain, China.
AB  - This study employed a modified DRASTIC model (AHP-DRASTIC model) and GALDIT model
      to evaluate the inherent vulnerability of shallow groundwater in Weibei Plain in
      Shandong Province of China and its vulnerability to seawater intrusion. The AHP
      DRASTIC model uses the analytic hierarchy process (AHP) to determine the weight
      of each parameter and reduces the subjectivity of evaluation. The vulnerability
      map generated by the AHP-DRASTIC model shows four types of vulnerability: high
      (25.0%), higher (28.0%), moderate (29.7%), and low (17.3%), and the high
      vulnerability areas are mainly distributed in the area north of Qingxiang Town
      and south of Changyi County. The distribution of high-vulnerability areas mainly
      related to the depth of groundwater table is 4-8 m, and the recharge of rainfall
      is 100-175 mm/year. The vulnerability map generated by the GALDIT model shows
      four types of vulnerability: high (33.5%), higher (23.4%), moderate (22.1%), and
      low (21.0%), and the high-vulnerability areas are mainly distributed in the
      coastal areas of Hanting District-Zhuli Town, the areas north of Linqu County,
      and the areas south of Shouguang County. The distribution of high-vulnerability
      areas mainly related to the distance between these areas and the coast is < 2.5
      km, with aquifer thickness > 15 m. Total dissolved solid, NO3-, Cl-, and SO42-
      are used to verify the accuracy of the DRASTIC model, the AHP-DRASTIC model, and
      the GALDIT model. The results show that the AHP-DRASTIC model is more suitable
      for the assessment of inherent vulnerability of shallow groundwater in the study
      area than the DRASTIC model, and human activities have a major impact on the
      verification of vulnerability and should be considered when conducting
      groundwater vulnerability verification. The results of this study can provide
      grounds for groundwater management and protection and land use planning in the
      study area and provide new ideas for groundwater vulnerability assessment in
      coastal areas.

PMID- 30238263
TI  - Green synthesis of silver and gold nanoparticles using Stemona tuberosa Lour and
      screening for their catalytic activity in the degradation of toxic chemicals.
AB  - In the present study, silver and gold nanoparticles (AgNPs and AuNPs) were green
      synthesised using the aqueous plant extract of Stemona tuberosa Lour. When plant
      extract was mixed with AgNO3 and HAuCl4 solutions in separate reactions, the
      amalgamated solutions turned deep reddish brown and dark purple in colour after
      48 h indicating the formation of AgNPs and AuNPs. UV-Visible analysis of green
      synthesised AgNPs and AuNPs have shown absorption maximum at 443.85 nm and 539.72
      respectively after 48 h. Energy dispersive X-ray spectroscopy (EDX) analysis
      confirmed the presence of pure silver in the green synthesised AgNPs and pure
      gold in the plant-mediated AuNPs. X-ray diffractometer (XRD) data revealed the
      face-centred cubic nature of AgNPs. Fluorescence transmission infrared (FTIR)
      spectrum has shown the characteristic peaks of different phytochemicals in the
      plant extract which acted as stabilising or capping agents of AgNPs. Scanning
      electron microscopy (SEM) analysis of AgNPs and AuNPs revealed that the
      nanoparticles are monodispersed. Transmission electron microscopy (TEM) studies
      revealed that AgNPs were mostly spherical with an average size of 25 nm whereas
      selected area electron diffraction (SAED) analysis confirmed their crystalline
      nature. Both AgNPs and AuNPs of S. tuberosa Lour have shown potential catalytic
      activity in the presence of sodium borohydride (NaBH4) in the degradation and
      removal of 4-nitrophenol, methylene blue, methyl orange and methyl red.

PMID- 30238264
TI  - Evaluation of phytotoxicity, cytotoxicity, and genotoxicity of ZnO nanoparticles
      in Vicia faba.
AB  - Due to the accelerating use of manufactured nanomaterials, more research is
      needed to define their impact on plants. The present investigation aimed at
      evaluating the effect of different levels (0.0, 10, 25, 50, and 100 mg/L) of ZnO
      nanoparticles (NPs) on Vicia faba during seed germination and seedling
      establishment. Additionally, V. faba root meristems were used as a model to
      monitor the cytotoxic and genotoxic effects resulting from exposure to ZnO NPs.
      The influence of ZnO NPs on three isoenzyme systems, peroxidase, alpha, and beta
      esterase, was also evaluated using native-PAGE. Our results showed that lower
      concentrations of ZnO NPs (especially 10 and 25 mg/L) enhanced seed germination
      and improved seedling growth, while higher concentrations (100 and 200 mg/L)
      resulted in phytotoxicity. Cytological investigations of ZnO NPs-treated V. faba
      root cells denoted the clastogenic and aneugenic nature of ZnO NPs. Differential
      increase in mitotic index and significant alterations in cell cycle were observed
      upon exposure to ZnO NPs. High concentrations of ZnO NPs markedly induced
      chromosomal aberration, micronuclei, and vacuolated nuclei formation. Chromosomal
      breakage, chromosomal bridges, ring chromosomes, laggard chromosomes, and
      stickiness were also observed at a higher rate. The PAGE analysis showed that ZnO
      NPs treatments altered the expression patterns of all studied enzyme systems.
      Collectively, results from this work will help to further understand the
      phytotoxic effects of nanomaterials.

PMID- 30238266
TI  - The 88-item Multiple Sclerosis Spasticity Scale: a Rasch validation of the
      Italian version and suggestions for refinement of the original scale.
AB  - BACKGROUND: In multiple sclerosis (MS), the impact of spasticity on the patient's
      life is a key issue, and it is fundamental that existing tools measuring the
      patient's perspective undergo psychometric analysis and refinement to optimize
      confidence in their use in clinical practice and research. OBJECTIVE: We examined
      by Rasch analysis (RA)-the main metric characteristics of the 88-item Multiple
      Sclerosis Spasticity Scale (MSSS-88) to: (i) further validate its Italian version
      (MSSS-88-IT), previously validated through classical test theory methods only and
      (ii) independently verify the measurement properties of the original scale.
      METHODS: MSSS-88 data from a convenience sample of 232 subjects with MS underwent
      RA, mainly examining item fit, reliability indices, test information function,
      dimensionality, local item independence, and differential item functioning (DIF).
      RESULTS: Most items fitted the Rasch model, but 13/88 items showed a misfit in
      infit and/or outfit values. Rasch reliability indices were high (> 0.80). Test
      information functions in most subscales showed a sharp decrease in measurement
      precision as the ability level departs from the quite limited central range of
      maximal information. The unidimensionality of each subscale was confirmed.
      Thirteen item pairs showed local dependency (residual correlations > 0.30) and
      three items presented DIF. CONCLUSION: Reliability, dimensionality and some
      internal construct validity characteristics of the MSSS-88-IT were confirmed.
      But, drawbacks of the original MSSS-88 emerged related to some item misfit,
      redundancy, or malfunctioning. Thus, further large independent studies are
      recommended, to verify the robustness of previous findings and examine the
      appropriateness of a few targeted item replacements.

PMID- 30238267
TI  - Anti-epileptics and pregnancy: an update.

PMID- 30238265
TI  - Effect of elevated benzophenone-4 (BP4) concentration on Chlorella vulgaris
      growth and cellular metabolisms.
AB  - Benzophenone-4 (BP4), as the raw material of common sunscreen products, usually
      shows strong eco-toxicity and endocrine-disrupting activity in aquatic animals.
      However, the potential adverse effect of BP4 on aquatic vegetation is still
      unclear. In order to evaluate the inhibitory effect of BP4 on phytoplankton, wild
      and acclimated Chlorella vulgaris was used as representative aquatic plant cells
      and experimental studies were conducted on the characteristics of its growth and
      cellular metabolisms upon exposure to elevated BP4 concentrations (1, 5, 10, 20,
      50, and 100 mg L-1). C. vulgaris basically appeared low sensitivity to BP4
      exposure because the 96-h EC50 was measured as 65.16 mg L-1 for its wild type.
      The 96-h EC50 of the acclimated type, which was pre-exposed to 10 mg L-1 of BP4
      and transferred twice, was 140.76 mg L-1. By cellular response tests regarding
      non-enzymatic antioxidants carotenoid content, malondialdehyde (MDA), enzyme
      antioxidant superoxide dismutase (SOD) activity, and the photosynthetic
      efficiency, it was clarified that increasing exposure concentration elevated the
      hindrance to cellular metabolism. However, the rate of BP4 utilization as
      substrates for C. vulgaris growth showed a trend of decreasing with increasing
      BP4 concentration. The higher 96-h EC50 value of the acclimated C. vulgaris to
      BP4 inhibition than the wild C. vulgaris showed the enhanced tolerance
      capability; however, the continuous stress response of acclimated type should be
      taken into account when using microalgae species for toxicity assessment.

PMID- 30238268
TI  - Prevalence of pain in atypical parkinsonism: a systematic review and meta
      analysis.
AB  - Pain is common in atypical parkinsonism such as multiple system atrophy (MSA),
      progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and
      dementia with Lewy bodies (LBD). In this study, a systematic review and meta
      analysis was conducted and peer-reviewed literature was searched to determine the
      prevalence and types of pain in four atypical parkinsonism syndromes: MSA, PSP,
      CBD and LBD. The results show that pain was prevalent mainly in MSA patients in
      comparison to PSP and CBD patients. Pain was reported at an early stage and was
      found in females, with limb pain being the most common, followed by neck and back
      pain. In comparison to PSP, pain locations were similar to MSA patients. CBD
      patients experienced pain the least in comparison to MSA, PSP and LBD patients.

PMID- 30238269
TI  - Does 22q11.2 deletion syndrome contribute to the genetic aetiology of Parkinson's
      disease?

PMID- 30238270
TI  - [Future perspective of the TraumaRegister DGU(r) : Further development,
      additional modules and potential limits].
AB  - Since its founding in 1993 the TraumaRegister DGU(r) has become one of the
      largest registries especially in terms of data diversity. Since the introduction
      of the TraumaNetzwerk DGU(r), the TraumaRegister DGU(r) has enabled a quasi
      nationwide picture of the quality of care of severely injured patients in
      Germany. The register is subject to constant development, under the guidance of
      the working groups of the German Society for Trauma Surgery (DGU). The first
      modular expansion of special injury entities (craniocerebral trauma and complex
      hand injuries) is currently taking place. The future developments will involve
      the extension of the register to certain injury patterns. The existing registry
      will also be supplemented with other recorded qualities (from the supplementary
      serum database up to the quality of life). This makes the TraumaRegister DGU(r) a
      tool for quality assurance and science which is well prepared for the future.

PMID- 30238271
TI  - Spatially-integrated estimates of net ecosystem exchange and methane fluxes from
      Canadian peatlands.
AB  - BACKGROUND: Peatlands are an important component of Canada's landscape, however
      there is little information on their national-scale net emissions of carbon
      dioxide [Net Ecosystem Exchange (NEE)] and methane (CH4). This study compiled
      results for peatland NEE and CH4 emissions from chamber and eddy covariance
      studies across Canada. The data were summarized by bog, poor fen and rich
      intermediate fen categories for the seven major peatland containing terrestrial
      ecozones (Atlantic Maritime, Mixedwood Plains, Boreal Shield, Boreal Plains,
      Hudson Plains, Taiga Shield, Taiga Plains) that comprise > 96% of all peatlands
      nationally. Reports of multiple years of data from a single site were averaged
      and different microforms (e.g., hummock or hollow) within these peatland types
      were kept separate. A new peatlands map was created from forest composition and
      structure information that distinguishes bog from rich and poor fen. National
      Forest Inventory k-NN forest structure maps, bioclimatic variables (mean diurnal
      range and seasonality of temperatures) and ground surface slope were used to
      construct the new map. The Earth Observation for Sustainable Development map of
      wetlands was used to identify open peatlands with minor tree cover. RESULTS: The
      new map was combined with averages of observed NEE and CH4 emissions to estimate
      a growing season integrated NEE (+/- SE) at - 108.8 (+/- 41.3) Mt CO2 season-1
      and CH4 emission at 4.1 (+/- 1.5) Mt CH4 season-1 for the seven ecozones.
      Converting CH4 to CO2 equivalent (CO2e; Global Warming Potential of 25 over 100
      years) resulted in a total net sink of - 7.0 (+/- 77.6) Mt CO2e season-1 for
      Canada. Boreal Plains peatlands contributed most to the NEE sink due to high CO2
      uptake rates and large peatland areas, while Boreal Shield peatlands contributed
      most to CH4 emissions due to moderate emission rates and large peatland areas.
      Assuming a winter CO2 emission of 0.9 g CO2 m-2 day-1 creates an annual CO2
      source (24.2 Mt CO2 year-1) and assuming a winter CH4 emission of 7 mg CH4 m-2
      day-1 inflates the total net source to 151.8 Mt CO2e year-1. CONCLUSIONS: This
      analysis improves upon previous basic, aspatial estimates and discusses the
      potential sources of the high uncertainty in spatially integrated fluxes,
      indicating a need for continued monitoring and refined maps of peatland
      distribution for national carbon and greenhouse gas flux estimation.

PMID- 30238273
TI  - Optimal duration of adjuvant trastuzumab in treatment of early breast cancer: a
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: One year of adjuvant trastuzumab, chosen empirically, improves
      survival of women with early-stage, Human Epidermal Growth Factor Receptor 2
      (HER2) positive breast cancer. Two years of trastuzumab does not improve efficacy
      but increases cost, inconvenience, and adverse effects. We aimed to evaluate if
      less than 1 year of adjuvant trastuzumab retained efficacy while reducing
      toxicities and cost. METHODS: We performed a pooled analyses of efficacy and
      toxicity from Randomized Controlled Trials (RCTs) comparing 1 year of trastuzumab
      to shorter durations in adjuvant treatment of HER2-positive breast cancer. Hazard
      Ratios (HR) for Overall Survival (OS) and Disease-Free Survival (DFS), and Odds
      Ratios (OR) for cardiac events with respective 95% Confidence Intervals (CI) were
      weighted using generic inverse variance approach and pooled in meta-analyses
      using random effects models with RevMan 5.3 software. Sub-group analyses of
      outcomes based on Estrogen Receptor (ER) and nodal status were performed.
      RESULTS: Five RCTs involving approximately 12,000 patients qualified-three
      assessing 6 months and two assessing 9 weeks of trastuzumab compared to 1 year.
      All RCTs were designed to test non-inferiority of the shorter treatment. One year
      of trastuzumab resulted into better OS (pooled HR 1.23, 95% CI 1.07-1.42) and DFS
      (pooled HR 1.21, 95% CI 1.09-1.36) in overall population, but the benefit of
      longer treatment was statistically insignificant in node negative (HR 1. 20, p =
      0.11), and ER positive disease (HR 1.15, p = 0.09). Odds ratio for cardiac events
      was significantly higher with the longer duration (OR 2.48, p < 0.001).
      CONCLUSION: One year of trastuzumab for adjuvant treatment of breast cancer
      improves outcomes compared to shorter treatments in overall population.
      Cardiotoxicity is increased with the longer treatment.

PMID- 30238272
TI  - Streptomyces albulus yields epsilon-poly-L-lysine and other products from salt
      contaminated glycerol waste.
AB  - Actinomycetes are the most important microorganisms for the industrial production
      of secondary metabolites with antimicrobial and anticancer properties. However,
      they have not been implicated in biorefineries. Here, we study the ability of the
      epsilon-poly-L-lysine producing Streptomyces albulus BCRC 11814 to utilize
      biodiesel-derived crude glycerol. S. albulus was cultured in a mineral medium
      supplemented with up to 10% w/v sodium chloride or potassium chloride, and with
      crude glycerol as the sole carbohydrate source. Under these conditions, the
      strain produced 0.1 g epsilon-poly-L-lysine per 1 g of biomass. RNA sequencing
      revealed upregulation of the ectoine biosynthetic pathway of S. albulus, which
      provides proof of halotolerance. S. albulus has several silent secondary
      metabolite biosynthetic clusters predicted within the genome. Based on the
      results, we conclude that S. albulus BCRC 11814 is a halotolerant microorganism
      capable of utilizing biodiesel-derived crude glycerol better than other
      actinomycetes included in the present study. S. albulus has the potential to be
      established as microbial platform production host for a range of high-value
      biological products.

PMID- 30238274
TI  - Isolated ipsilateral local recurrence of breast cancer: predictive factors and
      prognostic impact.
AB  - BACKGROUND: Tumour features associated with isolated invasive breast cancer (BC)
      ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and
      consequences on overall survival (OS) are still debated. Our objective was to
      investigate these points. METHODS: Patients were retrospectively identified from
      a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End
      points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate
      analysis (MVA) for all patients and according to endocrine receptors (ERs) and
      grade or tumour subtypes. RESULTS: Of 15,570 patients, ILR rate was 3.1%.
      Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p =
      0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p < 0.0001), endocrine
      therapy (HR 2.05, p < 0.0001) and age < 40-years old (HR 2.28, p = 0.005) in MVA.
      When MVA was adjusted on tumour subtype, the latter was the only independent
      factor. OS-after-ILR was significantly different according to ILR-free intervals
      (HR 4.96 for ILR-free interval between 2 and 5-years and HR 9.00 when < 2-years,
      in comparison with >= 5-years). CONCLUSION: ERs/Grade status, lack of endocrine
      therapy and tumour subtypes predict isolated ILR risk in patients treated with
      BCT. Short ILR-free-intervals represent a strong pejorative factor for OS. These
      results may help selecting initial treatment as well as tailoring ILR systemic
      chemotherapy.

PMID- 30238275
TI  - Is the high proportion of young age at breast cancer onset a unique feature of
      Asian breast cancer?
AB  - PURPOSE: Women with breast cancer in Asian and Western countries are similar in
      many respects, but there are also differences, such as in the age at onset and
      the proportion of breast cancer occurring at younger ages. There is controversy
      as to whether these differences are due to inter-racial genetic differences or to
      environmental or other factors. METHODS: Using the Korean Breast Cancer Society's
      large breast cancer registry, we investigated the causes of Koreans' unique
      breast cancer characteristics by examining the changes in the incidence and
      proportion of young-onset breast cancer (YBC) in Korea over time. We analyzed
      data from 108,894 patients to compare characteristics between patients with YBC
      and non-YBC. For a subtype analysis, we analyzed data from 85,691 patients from
      2000. RESULTS: Among the 108,894 patients, 17,877 (15.5%) had YBC. The tumors
      associated with YBC showed aggressive clinicopathologic features. The incidence
      of breast cancer in Korea has increased over time, and while both YBC and non-YBC
      increased each year, the increase in non-YBC was more pronounced; thus, the
      proportion of YBC has decreased over time. By 2020, it appears that the ratio of
      YBC in Korea will be similar to that in Western countries. The increase in YBC
      was mainly due to an increase in the luminal A subtype. The incidence of other
      YBC subtypes did not change over time. CONCLUSIONS: Our data suggest that the
      current high proportion of YBC is probably not a unique feature of breast cancer
      in Asia but rather a transient phenomenon. Additionally, our results indirectly
      suggest that there were different causes for breast cancer in different age
      groups, suggesting the importance of using different approaches for different age
      groups to establish policies for preventing breast cancer.

PMID- 30238276
TI  - Pathologic findings in reduction mammoplasty specimens: a surrogate for the
      population prevalence of breast cancer and high-risk lesions.
AB  - PURPOSE: Mammoplasty removes random samples of breast tissue from asymptomatic
      women providing a unique method for evaluating background prevalence of breast
      pathology in normal population. Our goal was to identify the rate of atypical
      breast lesions and cancers in women of various ages in the largest mammoplasty
      cohort reported to date. METHODS: We analyzed pathologic reports from patients
      undergoing bilateral mammoplasty, using natural language processing algorithm,
      verified by human review. Patients with a prior history of breast cancer or
      atypia were excluded. RESULTS: A total of 4775 patients were deemed eligible.
      Median age was 40 (range 13-86) and was higher in patients with any incidental
      finding compared to patients with normal reports (52 vs. 39 years, p = 0.0001).
      Pathological findings were detected in 7.06% (337) of procedures. Benign high
      risk lesions were found in 299 patients (6.26%). Invasive carcinoma and ductal
      carcinoma in situ were detected in 15 (0.31%) and 23 (0.48%) patients,
      respectively. The rate of atypias and cancers increased with age. CONCLUSION: The
      overall rate of abnormal findings in asymptomatic patients undergoing mammoplasty
      was 7.06%, increasing with age. As these results are based on random sample of
      breast tissue, they likely underestimate the prevalence of abnormal findings in
      asymptomatic women.

PMID- 30238278
TI  - CT-based mediastinal compartment classifications and differential diagnosis of
      mediastinal tumors.
AB  - Division of the mediastinum into compartments is used to help narrow down the
      differential diagnosis of mediastinal tumors, assess tumor growth, and plan
      biopsies and surgical procedures. There are several traditional mediastinal
      compartment classification systems based upon anatomical landmarks and lateral
      chest radiograph. Recently, the Japanese Association of Research of the Thymus
      (JART) and the International Thymic Malignancy Interest Group (ITMIG) proposed
      new mediastinal compartment classification systems based on transverse CT images.
      These CT-based classification systems are useful for more consistent and exact
      diagnosis of mediastinal tumors. In this article, we review these CT-based
      mediastinal compartment classifications in relation to the differential diagnosis
      of mediastinal tumors.

PMID- 30238277
TI  - Metal biomonitoring in a Patagonian salt marsh.
AB  - Patagonian salt marshes are not affected by pollution, but historical mining
      wastes are a continuous source of metals to salt marsh in San Antonio Bay. The
      present study evaluated the concentration of metals in sediments and used the
      halophyte Spartina spp. and the crab N. granulata as biomonitors. The levels of
      metals in sediment and organisms in SAB remained at levels corresponding to a
      slight enrichment or contamination. The highest levels corresponded to innermost
      sites of the Encerrado channel and close to the mining wastes. Spartina is a
      phytostabilizer so its aboveground tissues do not reflect the concentrations in
      the sediment; although, it retains the metals in its belowground tissues and in
      the rhizosediment. N. granulata showed to be a useful biomonitor for Pb, but not
      for the other metals.

PMID- 30238279
TI  - Large-scale analysis of small RNAs derived from traditional Chinese herbs in
      human tissues.
AB  - Plant-derived microRNAs have recently been reported to function in human blood
      and tissues. Controversy was immediately raised due to possible contamination and
      the lack of large sample sizes. Here, we report thousands of unique small RNAs
      derived from traditional Chinese medicine (TCM) herbs found in human blood cells
      and mouse lung tissues using a large-scale analysis. We extracted small RNAs from
      decoctions of 10 TCM plants (Ban Zhi Lian, Chai Hu, Chuan Xin Lian, Di Ding Zi
      Jin, Huang Qin, Jin Yin Hua, Lian Qiao, Pu Gong Ying, Xia Ku Cao, and Yu Xing
      Cao) and obtained millions of RNA sequences from each herb. We also obtained RNA
      Seq data from the blood cells of humans who consumed herbal decoctions and from
      the lung tissues of mice administered RNAs from herbal decoctions via oral
      gavage. We identified thousands of unique small RNA sequences in human blood
      cells and mouse lung tissues. Some of these identified small RNAs from Chuan Xin
      Lian and Hong Jing Tian could be mapped to the genomes of the herbs, confirming
      their TCM plant origin. Small RNAs derived from herbs regulate mammalian gene
      expression in a sequence-specific manner, and thus are a superior novel class of
      herbal drug components that hold great potential as oral gene-targeted
      therapeutics, highlighting the important role of herbgenomics in their
      development.

PMID- 30238280
TI  - Protective effects of autophagy against blue light-induced retinal degeneration
      in aged mice.
AB  - The aim of this study was to explore the role of autophagy in response to blue
      light damage in aged mice and in human retinal pigmented epithelium (hRPE) cells.
      Blue light damage to the retina was induced in 10-month-old (10 mo) C57 mice and
      hRPE cells. Flash electroretinography was used to assess retinal function.
      Retinal structure changes were observed by electron microscopy. Western blot was
      conducted to determine the expression levels of the following proteins: cleaved
      caspase-3, p38 mitogen-activated protein kinases, protein kinase R-like
      endoplasmic reticulum kinase (PERK), autophagy marker light chain 3 (LC3), P62,
      and Beclin-1. On day 1 after light damage to the 10 mo mice, retinal function was
      changed. The latent periods of a-wave and b-wave were delayed, and amplitude was
      reduced. The electron microscopy results revealed mitochondria damage in the
      retinal pigmented epithelium and a disorganized photoreceptor outer segment (OS).
      PERK, LC3, and Beclin-1 were upregulated, whereas P62 was not. On day 5 after the
      blue light damage, restoration of electroretinography and OS was observed. PERK,
      LC3, and Beclin-1 were downregulated, whereas P62 was not. Protein changes in
      vitro were consistent with in vivo. The present study provided structural and
      functional evidence that autophagy plays an important role in the response to
      blue lightinduced retinal damage.

PMID- 30238281
TI  - Correction to: Gender Differences and Prevalence of Mental Health Problems in
      Students of Healthcare Units.
AB  - The original version of this article unfortunately contained a typo in the author
      name. The co-author name should be Ahsan Ehtesham instead it was published as
      Ahsan Ehtisham.

PMID- 30238282
TI  - Stakeholders' Views Regarding Their Role as Support System for People with Mental
      Illness and Their Families in Rural South Africa.
AB  - The diverse needs associated with mental illness warrant for the provision of
      mental health care by various sources. The South African government recognises
      the involvement of stakeholders as a potential means of narrowing the gaps in
      mental health service delivery. This study explored the views of different
      stakeholders about their roles as support systems for people with mental illness
      and their families at Mashashane, a rural setting in Limpopo Province, South
      Africa. Seven focus group discussions were conducted with various stakeholders.
      This qualitative study employed content analysis to allow for comparison of
      stakeholders' views. Stakeholders understanding of mental illness was based on
      reaction towards people with mental illness, causes of mental illness and the
      behaviour displayed by the ill individual. The identified formal and informal
      systems were seen as ineffective with regards to provision of support.
      Collaboration was recommended as a mechanism to improve mental health services.
      The findings contributed in the formulation of guidelines to improve support.

PMID- 30238283
TI  - Correction to: Criteria for the definition of Pituitary Tumor Centers of
      Excellence (PTCOE): A Pituitary Society Statement.
AB  - The original version of this article unfortunately contained an affiliation error
      in 'Collaborators for The Pituitary Society, Expert Group on Pituitary Tumors'
      section. Dr. Misa Pfeifer is affiliated with Medical Faculty, University of
      Ljubljana, Slovenia and the correct email address to contact is
      misa.pfeifer@gmail.com.

PMID- 30238284
TI  - Association between obstructive sleep apnea syndrome and waist-to-height ratio.
AB  - PURPOSE: Obesity is among the known risk factors for obstructive sleep apnea
      syndrome (OSAS). In this study, our aim was to investigate the correlation of
      waist-to-height ratio, an indicator of central obesity, with presence and
      severity of OSAS; to compare the use of this ratio with the use of waist
      circumference and body mass index (BMI); and to determine OSAS-related cutoff
      values. METHODS: The patient records were retrospectively analyzed for whom a
      polysomnography was conducted at our sleep. Sex, age, Apnea-Hypopnea Index (AHI),
      waist circumference, height, and BMI values of those patients were recorded. AHI
      scores were used to classify severity of OSAS. RESULTS: The study included 437
      OSAS patients and 72 control cases. Out of the patient group, OSAS was severe in
      208 (47%) patients, moderate in 124 (28%), and mild in 105 (24%) of them. In the
      group of OSAS patients, waist-to-height ratio, waist circumference, and BMI were
      higher compared to the control group with a further difference of all three
      parameters among severe, moderate, mild OSAS, and controls both in males and
      females. Cutoff values for OSAS of females were 95.5 cm for waist circumference,
      0.595 for waist-to-height ratio, and 27.75 for BMI whereas the cutoff values of
      males were 100.5 cm, 0.575, and 27.75, respectively. CONCLUSIONS: A high value of
      waist circumference, waist-to-height ratio, and BMI is associated with the
      presence and severity of OSAS. We have determined the cutoff values of the
      studied anthropometric measurements in both sexes for OSAS and severe OSAS.

PMID- 30238285
TI  - Solitary extramedullary plasmacytoma of the rectum complicating ulcerative
      colitis.
AB  - Solitary extramedullary plasmacytoma (EMP) arising in the rectum is an extremely
      rare clinical entity. Only ten cases have been reported in the English-language
      literature. We experienced a case of an EMP in the rectum of a 55-year-old man
      with an 8-year history of proctitis-type ulcerative colitis (UC). The
      plasmacytoma appeared as an 8-mm semipedunculated polypoid lesion in the actively
      inflamed rectal mucosa when the remittent UC flared. The tumor was treated using
      endoscopic mucosal resection. This is the second case of rectal EMP associated
      with UC after a similar report was published in 2004. Both patients had a chronic
      history of proctitis-type UC and were taking no immunosuppressive agents that
      could cause Epstein-Barr virus-associated plasmacytoma, such as thiopurines. The
      UC activity seemed to correspond well with the development of the rectal EMP.
      Therefore, we herein discuss a possible association between rectal EMP and UC and
      review the past literature of rectal EMP.

PMID- 30238287
TI  - [Atypical presentation of depression leading to delay in treatment].
AB  - Major depression can present with atypical symptomatology and as a consequence,
      delay can occur in passing through the relevant algorithm for biological
      treatment. The case of a 62-year old female is presented who eventually was
      diagnosed with a major depressive episode, with psychotic features. The atypical
      presentation led to persistent diagnostic uncertainty both during outpatient
      treatment in several mental health care institutions and during inpatient
      observation. As a consequence, proceeding to the next step of the algorithm for
      biological treatment for major depression was delayed. Factors involved in this
      diagnostic uncertainty are discussed.

PMID- 30238286
TI  - [The behavioral and psychological symptoms of dementia in down syndrome (BPSD-DS)
      scale: comprehensive assessment of psychopathology in down syndrome].
AB  - Behavioral and psychological symptoms of dementia (BPSD) have not been
      comprehensively studied in people with Down syndrome, despite their high risk on
      dementia. A novel evaluation scale was developed to identify the nature,
      frequency and severity of behavioral changes (83 behavioral items in 12
      clinically defined sections). Central aim was to identify items that change in
      relation to the dementia status. Structured interviews were conducted with
      informants of people with Down syndrome without dementia (DS, N = 149), with
      questionable dementia (DS + TD, N = 65) and with diagnosed dementia (DS + AD, N =
      67). Group comparisons showed a pronounced increase in frequency and severity of
      items about anxiety, sleep disturbances, agitation & stereotypical behavior,
      aggression, apathy, depressive symptoms, and, eating/drinking behavior. The
      proportion of individuals presenting an increase was highest in the DS + AD group
      and lowest in the DS group. Interestingly, among DS + TD individuals, a
      substantial proportion already presented increased anxiety, sleep disturbances,
      apathy and depressive symptoms, suggesting that these changes may be early alarm
      signals of dementia. The scale may contribute to a better understanding of the
      changes, adapting daily care/support, and providing suitable therapies to people
      with Down syndrome. The scale needs to be optimized based on the results and
      experiences. The applicability, reliability and validity require further study.

PMID- 30238288
TI  - [Autoimmune reactions and paraneoplastic syndromes].
AB  - CLINICAL ISSUE: Autoimmune disorders of the central nervous system (CNS) are
      common but are also a heterogeneous group of diseases. The most common form is
      multiple sclerosis (MS), others are clinically isolated syndrome (CIS), acute
      demyelinating encephalomyelitis (ADEM) and neuromyelitis optica spectrum
      disorders (NMOSD). Paraneoplastic syndromes are rare and tumor-associated, they
      are not induced by direct invasion of tumor tissue but by tumor-associated
      autoantibodies mostly against specific CNS proteins, e. g. limbic encephalitis
      and paraneoplastic cerebellar ataxia or degeneration. DIAGNOSTICS, STANDARD
      RADIOLOGICAL METHODS, PERFORMANCE AND ACHIEVEMENTS: The correct diagnosis of
      autoimmune and paraneoplastic syndromes can still be challenging. In addition to
      the patient history, clinical examination and blood as well as cerebrospinal
      fluid (CSF) tests, magnetic resonance imaging (MRI) is gaining importance in the
      diagnostics. It is important not only in primary diagnostics but also in follow
      up and therapy monitoring, especially in MS with specific therapies to detect
      therapy complications, such as progressive multifocal leukoencephalopathy as
      early as possible. In paraneoplastic syndromes MRI can also be an important
      component in the diagnostics but can also initially be negative and typical
      signal changes become visible only in follow-up scans. PRACTICAL RECOMMENDATIONS:
      In paraneoplastic syndromes the correct diagnosis is based on laboratory tests
      for specific autoantibodies in serum and CSF. TREATMENT: The treatment of
      autoimmune and paraneoplastic disorders of the CNS ranges from steroids and
      immunosuppressive agents to plasmapheresis, depending on the specific disorder.

PMID- 30238289
TI  - [Damages to the central nervous system due to illicit drug use].
AB  - CLINICAL ISSUE: Illicit drugs can cause a myriad of CNS damages. The toxicity
      might be caused by the drug itself or by diverse contaminants. The most common
      changes are ischemic and hemorrhagic stroke as well as subarachnoid hemorrhage
      and leukoencephalopathies. This article gives a review of the most important
      morphological imaging findings of the CNS in illicit drug users. PRACTICAL
      RECOMMENDATIONS: In cases of stroke or unclear leukoencephalopathies in young
      adults, the differential diagnosis of illicit drug use should be considered.

PMID- 30238292
TI  - Health Services Use Among Jailed Women with Alcohol Use Disorders.
AB  - Correctional facilities now house unprecedented numbers of women with complex
      treatment needs. This investigation applied the Behavioral Model for Vulnerable
      Populations to study 168 jailed women with alcohol use disorders. It described
      the sample's predisposing (age, race, victimization), enabling (health
      insurance), and need (self-reported medical, substance use, and mental health
      problems) factors and examined associations of these factors with pre
      incarceration services utilization. Most participants had clinically significant
      levels of depression and PTSD symptoms, most took psychiatric medications, and
      most had been victimized. Participants reported considerable health services
      utilization. Younger, Black, and uninsured women utilized fewer medical and
      mental health services. Drug use was associated with less use of medical
      services, but more use of alcohol and drug services. High rates of health
      services use support the need for integrated, ongoing care for substance-using
      women before, during, and after incarceration.

PMID- 30238290
TI  - [Normal variants and pitfalls at the elbow joint].
AB  - The elbow joint is comprised of three different bones with a combined hinge and a
      ball joint. Several nerves, tendons and muscles cross the joint. Anatomical
      variations at the elbow are common and may be the cause of certain pathologies.
      Despite the high quality of modern cross-sectional imaging, certain normal
      findings on CT or MRI have the risk of being misinterpreted. This article
      describes more common but also rare, normal variants around the elbow joint.
      Classic pitfalls are illustrated and compared to similar pathological findings.

PMID- 30238293
TI  - Getting a grasp on action-specific scaling: A response to Witt (2017).
AB  - Can higher level cognition directly influence visual spatial perception? Many
      recent studies have claimed so, on the basis that manipulating cognitive factors
      (e.g., morality, emotion, action capacity) seems to directly affect perception.
      However, Firestone and Scholl (Behavioral and Brain Sciences, 39, 1-77, 2016)
      argued that such studies often fall prey to at least one of six pitfalls. They
      further argued that if an effect could be accounted for by any of these pitfalls,
      it is not a true demonstration of a top-down influence of cognition on
      perception. In response to Firestone and Scholl (Behavioral and Brain Sciences,
      39, 1-77, 2016), Witt (Psychonomic Bulletin & Review, 24(4), 999-1021, 2017)
      discussed four action-specific scaling effects which, she argued, withstand all
      six pitfalls and thus demonstrate true perceptual changes caused by differences
      in action capacity. Her third case study was the influence of apparent grasping
      capacity on perceived object size. In this article, we provide new
      interpretations of previous findings and assess recent data which suggest that
      this effect is not, in fact, perceptual. Instead, we believe that many earlier
      studies showing this effect are subject to one or more of the pitfalls outlined
      by Firestone and Scholl (Behavioral and Brain Sciences, 39, 1-77, 2016). We
      substantiate our claims with recent empirical evidence from our laboratory which
      suggests that neither actual nor perceived grasping capacity directly influence
      perceived object size. We conclude that studies manipulating grasping capacity do
      not provide evidence for the action-specific account because variation in this
      factor does not directly influence size perception.

PMID- 30238294
TI  - There is music in repetition: Looped segments of speech and nonspeech induce the
      perception of music in a time-dependent manner.
AB  - While many techniques are known to music creators, the technique of repetition is
      one of the most commonly deployed. The mechanism by which repetition is effective
      as a music-making tool, however, is unknown. Building on the speech-to-song
      illusion (Deutsch, Henthorn, & Lapidis in Journal of the Acoustical Society of
      America, 129(4), 2245-2252, 2011), we explore a phenomenon in which perception of
      musical attributes are elicited from repeated, or "looped," auditory material
      usually perceived as nonmusical such as speech and environmental sounds. We
      assessed whether this effect holds true for speech stimuli of different lengths;
      nonspeech sounds (water dripping); and speech signals decomposed into their
      rhythmic and spectral components. Participants listened to looped stimuli (from
      700 to 4,000 ms) and provided continuous as well as discrete perceptual ratings.
      We show that the regularizing effect of repetition generalizes to nonspeech
      auditory material and is strongest for shorter clip lengths in the speech and
      environmental cases. We also find that deconstructed pitch and rhythmic speech
      components independently elicit a regularizing effect, though the effect across
      segment duration is different than that for intact speech and environmental
      sounds. Taken together, these experiments suggest repetition may invoke active
      internal mechanisms that bias perception toward musical structure.

PMID- 30238295
TI  - The influence of everyday events on prospective timing "in the moment".
AB  - We conducted two experiments to investigate how the eventfulness of everyday
      experiences influences people's prospective timing ability. Specifically, we
      investigated whether events contained within movies of everyday activities serve
      as markers of time, as predicted by Event Segmentation Theory, or whether events
      pull attention away from the primary timing task, as predicted by the Attentional
      Gate theory. In the two experiments reported here, we asked participants to
      reproduce a previously learned 30-s target duration while watching a movie that
      contained eventful and uneventful intervals. In Experiment 2, reproduction also
      occurred during "blank movies" while watching a fixation. In both experiments,
      participants made shorter and more variable reproductions while simultaneously
      watching eventful as compared to uneventful movie intervals. Moreover, in
      Experiment 2, the longest reproductions were produced when participants had to
      watch the blank movies, which contained no events. These results support Event
      Segmentation Theory and demonstrate that the elapsing events during prospective
      temporal reproduction appear to serve as markers of temporal duration rather than
      distracting from the timing task.

PMID- 30238296
TI  - Perceptual proxies for extracting averages in data visualizations.
AB  - Across science, education, and business, we process and communicate data
      visually. One bedrock finding in data visualization research is a hierarchy of
      precision for perceptual encodings of data (e.g., that encoding data with
      Cartesian positions allows more precise comparisons than encoding with sizes).
      But this hierarchy has only been tested for single-value comparisons, under the
      assumption that those lessons would extrapolate to multivalue comparisons. We
      show that when comparing averages across multiple data points, even for pairs of
      data points, these differences vanish. Viewers instead compare values using
      surprisingly primitive perceptual cues (e.g., the summed area of bars in a bar
      graph). These results highlight a critical need to study a broader constellation
      of visual cues that mediate the patterns that we can see in data, across
      visualization types and tasks.

PMID- 30238297
TI  - Takayasu arteritis detected by PET/MRI with 18F-fluorodeoxyglucose.

PMID- 30238298
TI  - Sub-endocardial and sub-epicardial measurement of myocardial blood flow using
      13NH3 PET in man.
AB  - BACKGROUND: This study examined whether measuring myocardial blood flow (MBF) in
      the sub-endocardial (SEN) and sub-epicardial (SEP) layers of the left ventricular
      myocardium using 13NH3 positron emission tomography (PET) and an automated
      procedure gives reasonable results in patients with known or suspected coronary
      artery disease (CAD). METHODS: Resting and stress 13NH3 dynamic PET were
      performed in 70 patients. Using >= 70% diameter stenosis in invasive coronary
      angiography (ICA) to identify significant CAD, we examined the diagnostic value
      of SEN- and SEP-MBF, and coronary flow reserve (CFR) vs. the corresponding
      conventional data averaged on the whole wall thickness. RESULTS: ICA demonstrated
      36 patients with significant CAD. Their global stress average [1.61 (1.26, 1.87)
      mL.min-1.g-1], SEN [1.39 (1.2, 1.59) mL.min-1.g-1] and SEP [1.22 (0.96, 1.44)
      mL.min-1.g-1] MBF were significantly lower than in the 34 no-CAD patients: 2.05
      (1.76, 2.52), 1.72 (1.53, 1.89) and 1.46 (1.23, 1.89) mL.min-1.g-1, respectively,
      all P < .005. In the 60 CAD vs. the 150 non-CAD territories, stress average MBF
      was 1.52 (1.10, 1.83) vs. 2.06 (1.69, 2.48) mL.min-1.g-1, SEN-MBF 1.33 (1.02,
      1.58) vs. 1.66 (1.35, 1.93) mL.min-1.g-1, and SEP-MBF 1.07 (0.80, 1.29) vs. 1.40
      (1.12, 1.69) mL.min-1.g-1, respectively, all P < .05. Using receiver operating
      characteristics analysis for the presence of significant CAD, the areas under the
      curve (AUC) were all significant (P < .0001 vs. AUC = 0.5) and similar: stress
      average MBF = 0.79, SEN-MBF = 0.75, and SEP-MBF = 0.73. AUC was 0.77 for the
      average CFR, 0.75 for SEN, and 0.70 for SEP CFR. The stress transmural perfusion
      gradient (TPG) AUC (0.51) was not significant. However, stress TPG was
      significantly lower in segments subtended by totally occluded arteries vs. those
      subtended by sub-total stenoses: 1.10 (0.86, 1.33) vs. 1.24 (0.98, 1.56),
      respectively, P < .005. CONCLUSION: Automatic assessment of SEN- and SEP-MBF (and
      CFR) using 13NH3 PET gives reasonable results that are in good agreement with the
      conventional average whole wall thickness data. Further studies are needed to
      examine the utility of layer measurements such as in patients with hibernating
      myocardium or microvascular disease.

PMID- 30238299
TI  - Intersoftware variability impacts classification of cardiac PET exams.
AB  - BACKGROUND: Myocardial perfusion imaging (MPI) with 82Rb PET/CT is increasingly
      utilized in the evaluation of coronary artery disease with high diagnostic
      accuracy. Various softwares for data processing have been developed over the
      years with conflicting data regarding their reproducibility. In this study, we
      compared the quantitative results of myocardial perfusion and exam classification
      from three different softwares. METHODS: Data from consecutive patients who have
      undergone rest/stress 82Rb PET/CT MPI at the Royal Brompton & Harefield Trust,
      London, were analyzed. All data were processed using the Corridor 4DM (Invia, Ann
      Arbor, Michigan, USA), QPET (Cedars-Sinai, Los Angeles, California, USA), and
      SyngoMBF (Siemens Healthineers, Erlangen, Germany). The software packages
      addressed Lortie tracer kinetic model and region of interest (ROI) extraction
      correction option. STATISTICS: A repeated-measures ANOVA with a Greenhouse
      Geisser correction was performed with post hoc tests using Bonferroni correction.
      For intersoftware variability, Pearson correlation and intraclass correlation
      coefficients (ICC) were calculated. Bland-Altman assessed limit of agreement.
      Cohen's Kappa assessed agreement in the classification of exams as normal or
      abnormal using an MFR cut-off value of 2.0. A P value of less than 0.05 was
      considered statistically significant. RESULTS: Data from 55 patients were
      analyzed. The mean values of myocardial blood flow (MBF) and myocardial perfusion
      reserve (MFR) were statistically significantly different among the softwares (P <
      0.05). Corridor4DM had considerably lower values of MFR and classified a more
      substantial number of exams as abnormal (MFR: 2.21 +/- 0.7, 2.4 +/- 0.8, and 1.98
      +/- 0.8; and 18, 15, and 31 exams were abnormal for Syngo, QPET, and Corridor4DM,
      respectively). Accordingly, kappa agreement was moderate for Syngo vs QPET (k >
      0.5), but minimal for Corridor4DM in comparison to its pairs (k < 0.4).
      CONCLUSION: Users should be cautious when using different software
      interchangeably as systematic differences amongst them may introduce more
      extensive quantitative variation which could be clinically significant.

PMID- 30238300
TI  - Stop that glucose getting to heart!
AB  - Cardiac inflammation/infection imaging with 18F-FDG has been very useful in
      guiding patient management in conditions such as cardiac sarcoidosis,
      myocarditis, device infections, and prosthetic implant-related infections.
      Various protocols have been described to suppress normal myocardial glucose
      uptake. Certainly, there is need for standardization of protocols but adaptation
      of protocol to suit individual patient needs is also equally important. In the
      current article in this issue, Alexandra Clement et al have shown that a 7-day
      ketogenic diet can be used as an alternative method in mice models. This may work
      well in humans who are unable to fast.

PMID- 30238301
TI  - Association between non-alcoholic fatty liver disease and myocardial glucose
      uptake measured by 18F-fluorodeoxyglucose positron emission tomography.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as an
      independent risk factor for cardiovascular diseases. However, there were few
      studies evaluating the condition of myocardial glucose metabolism in patients
      with NAFLD. Therefore, the aim of this study was to investigate the association
      between NAFLD and myocardial glucose uptake assessed by using 18F
      fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and whether or
      not alteration of myocardial glucose uptake could be an indicator linking to
      cardiac dysfunction in NAFLD individuals. METHODS AND RESULTS: A total of 743
      asymptomatic subjects (201 with NAFLD, 542 without NAFLD) were retrospectively
      studied. The ratio of maximum myocardium FDG uptake to the mean standardized
      uptake value of liver (SUVratio) was calculated to estimate myocardial glucose
      uptake by using 18F-FDG PET. The diagnosis of fatty liver and fatty liver grading
      was confirmed by unenhanced CT according to diagnostic criterion of previous
      studies. The myocardial geometric and functional data were obtained by
      echocardiogram. Myocardial glucose uptake was significantly lower in individuals
      with NAFLD compared with those without fatty liver (P < .001). When analysis of
      association trend was performed, SUVratio quartiles showed correlated inversely
      and strongly with liver steatosis (P < .001). NAFLD patients with lower
      myocardial glucose uptake were more likely to have higher proportion of increased
      LV filling pressure (P < .05). A significant relationship between myocardial
      SUVratio and E/e' ratio was presented in the trend analysis (P < .05). Moreover,
      multivariate regression analysis showed that myocardial glucose uptake was
      independently associated with NAFLD after adjusting for clinical important
      factors (all P < .001). CONCLUSIONS: The presence of NAFLD in otherwise healthy
      subjects is closely associated with decreased myocardial glucose uptake assessing
      by 18F-FDG PET imaging. Furthermore, the NAFLD individuals with lower myocardial
      glucose uptake are more likely to have high risk of having impaired diastolic
      heart function.

PMID- 30238302
TI  - Correct species identification (reclassification in CNCTC) of strains of
      Staphylococcus intermedius-group can improve an insight into their evolutionary
      history.
AB  - A group of 59 putative strains of Staphylococcus intermedius/Staphylococcus
      pseudintermedius deposited in the Czech National Collection of Type Cultures
      (CNCTC, National Institute for Public Health, Prague, Czech Republic) and the
      National Reference Laboratory for Staphylococci (NRL for Staphylococci, National
      Institute for Public Health, Prague, Czech Republic) was reclassified using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      There the biggest human collection of S. pseudintermedius in Europe was analysed;
      44 samples (75%) were of human origin. Twenty-two percent (n = 13) of the strains
      were isolated from animals, and two staphylococci were of unknown origin. This
      study revealed the prevalence of Staphylococcus pseudintermedius (94%, n = 53)
      vs. Staphylococcus intermedius (6%, n = 6) in the collection of human and
      veterinary staphylococci after reclassification. Results of PCR-RFLP analysis
      were verified by comparison with a repetitive element sequence-based polymerase
      chain reaction (Rep-PCR) analysis on 26 (44%) randomly selected strains. Due to a
      low-resolution ability of PCR-RFLP to separate Staphylococcus intermedius from
      Staphylococcus delphini, four isolates of Staphylococcus intermedius were
      biochemically verified further to exclude the presence of Staphylococcus delphini
      in the collection. Our results indicate that S. intermedius and S.
      pseudintermedius have occurred independently over an age-long period of their co
      evolution.

PMID- 30238303
TI  - Preparation and Evaluation of Probucol-Phospholipid Complex with Enhanced
      Bioavailability and No Food Effect.
AB  - To enhance the oral bioavailability and eliminate the food effect of probucol.
      Probucol-phospholipid complex was prepared using solvent-evaporation method in
      this research. Several methods were used to validate the formation of complexes,
      such as FT-IR, SEM, DSC and PXRD, and the solubility of PRO and PRO-PLC was
      detected by HPLC. Pharmacokinetic testing was conducted in the fasted and fed
      state. FTIR, SEM, DSC and PXRD validated the existence of PRO-PLC. The solubility
      of PRO in complexes was 15.05 MUg/mL, which was 215-fold of the PRO-API. The
      dissolution rate was increased by preparing PRO-PLC. Compared with commercial
      tablets, the PRO-PLC complexes exhibited higher peak plasma concentration (1.69
      +/- 0.44 MUg/mL), increased AUC0-24 h (6.8 +/- 1.3 MUg/mL h), which mean the
      bioavailability of PRO was increased. In addition, the absorption of PRO was not
      interfered with food. In conclusion, an improved solubility and bioavailability
      was achieved with the preparation of PRO-PLC. Additionally, the dissolution
      behaviour was good and the food effect was eliminated.

PMID- 30238304
TI  - Composite Microparticles Based on Natural Mucoadhesive Polymers with Promising
      Structural Properties to Protect and Improve the Antifungal Activity of
      Miconazole Nitrate.
AB  - Oropharyngeal candidiasis is a recurrent oral infection caused by Candida
      species. Gel formulation containing miconazole nitrate is the most common
      approach for treating oral candidiasis. However, traditional oral topical
      antifungal therapies have many limitations, including short contact time with the
      oral mucosa and the necessity to administrate various doses per day. Thus, the
      aim of this work was to formulate composited microparticulated systems based on
      combinations of mucoadhesive cationic, anionic, and nonionic polymers that could
      protect and modify the drug release rate and therefore avoid a fast dilution of
      the drug by saliva. Microparticulated systems were prepared by the spray drying
      method employing chitosan, gelatin, and hydroxypropyl methylcellulose. The
      morphology of the systems was investigated by scanning electron microscopy; drug
      crystallinity was studied by X-ray, while interactions between polymers were
      analyzed by infrared spectroscopy. Drug release and halo zone test were employed
      to analyze the release and activity of the systems loaded with miconazole against
      Candida albicans cultures. The most appropriate microparticulated system was the
      one based on chitosan and gelatin which showed homogeneous morphology (mean size
      of 1.7 +/- 0.5 MUm), a protective effect of the drug, and better antifungal
      effect against Candida culture than miconazole nitrate and the other assayed
      systems. Taking into account these results, this approach should be seriously
      considered for further evaluation of its safety and in vivo efficacy to be
      considered as an alternative therapeutic system for the treatment of oral
      candidiasis.

PMID- 30238305
TI  - Oral Brain-Targeted Microemulsion for Enhanced Piperine Delivery in Alzheimer's
      Disease Therapy: In Vitro Appraisal, In Vivo Activity, and Nanotoxicity.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that has no cure till
      now. Piperine (PIP) is an alkaloid characterized by memory-enhancing properties
      but challenging oral delivery obstacles. The objectives of this study are as
      follows: preparation of microemulsion (ME) as a proposed oral PIP nanocarrier for
      treatment of Alzheimer's disease and testing its safety on the brain and other
      internal organs. This study employs bioactive surfactants in the common safe
      doses to improve PIP targeting to the brain. Selected ME systems encompassed
      Caproyl 90 (oil)/Tween 80/Cremophor RH 40 (surfactant) and Transcutol HP (co
      surfactant). The particle size of the prepared formulations was less than 150 nm
      with negative zeta potential. The in vivo results showed a superior effect of ME
      over free PIP. Colchicine-induced brain toxicity results showed the safety of ME
      on brain cells. Nevertheless, toxicological results showed a potential ME
      nephrotoxicity. Oral microemulsion increased PIP efficacy and enhanced its
      delivery to the brain resulting in better therapeutic outcome compared to the
      free drug. However, the toxicity of this nanosystem should be carefully taken
      into consideration on chronic use.

PMID- 30238306
TI  - Genetic variability and pyrethroid susceptibility of the parasitic honey bee mite
      Varroa destructor (Acari: Varroidae) in Iran.
AB  - The ectoparasitic honey bee mite Varroa destructor Anderson & Trueman (Acari:
      Varroidae) is one of the major concerns for worldwide beekeeping. The use of
      synthetic pyrethroids for controlling the mite was among the most popular
      treatments until resistance evolved in the mid 1990's. In Iran, beekeepers are
      dealing with the parasite and they also used pyrethroids for controlling the mite
      for a long time. After the evolution of resistance to pyrethroids, they based
      mite control mostly on treatments with amitraz, organic acids and several
      management practices. Here we conducted a comprehensive characterization of V.
      destructor populations parasitizing Apis mellifera in Iran. We determined the
      genetic variability of mites collected from 28 localities distributed throughout
      the country. The haplotype of V. destructor was determined by PCR-RFLP, analyzing
      a fragment of the mitochondrial cox1 gene. It was found that only the Korean
      haplotype was present in samples from all localities. DNA fragments from cox1,
      atp6, cox3 and cytb mitochondrial genes were sequenced and the results showed
      that all samples were identical to the K1-1 or the K1-2 V. destructor haplotypes.
      Moreover, as it has been reported that resistance to pyrethroids in V. destructor
      is associated with mutations at position 925 of the voltage-gated sodium channel,
      a TaqMan(r)-based allelic discrimination assay was conducted to genotype the
      mites collected. The results showed that all the mites tested were homozygous for
      the wild-type allele and, therefore, susceptible to treatment with pyrethroids.

PMID- 30238308
TI  - Water mite (Acari: Hydrachnidia) diversity and distribution in undisturbed
      Dinaric karst springs.
AB  - Large undisturbed karst springs in the Dinaric region are particularly
      interesting and extremely valuable and rare ecosystems, housing diverse and yet
      undiscovered water mite species. The complex life history traits of water mites
      include several life stages that are interconnected with other freshwater
      arthropod groups, making them important components of freshwater fauna. This
      study examined whether the differences in water mite assemblages between
      Mediterranean and alpine karst springs were driven by seasonal and/or regional
      changes in environmental conditions. The first ecological data on water mite
      dynamics and distribution in the Dinaric region of Croatia are presented. Water
      mites were represented by 11 taxa, decreasing in taxon richness from alpine to
      Mediterranean springs. Spatial patterns of water mite assemblages at the regional
      scale were best explained by water temperature, dissolved oxygen and water
      velocity. Pseudotorrenticola rhynchota and Oxus setosus were exclusively found in
      springs with higher water temperature and velocity, whereas the genera Aturus sp.
      and Woolastookia rotundifrons were exclusively recorded in the alpine springs,
      where oxygen concentrations were significantly higher. Atractides sp., Lebertia
      sp. and Sperchon sp. were recorded in most springs. Water mite abundances had a
      summer peak in the Mediterranean region, whereas two smaller peaks were observed
      in the spring and fall in the alpine region. Regional differences in the
      seasonality of water mite abundance were most likely patterned by the emergence
      of insect crenofauna.

PMID- 30238307
TI  - Genetic variability of wildlife-derived Sarcoptes scabiei determined by the
      ribosomal ITS-2 and mitochondrial 16S genes.
AB  - Infestation by the ectoparasitic mite Sarcoptes scabiei (Acari: Sarcoptidae) has
      important implications for global wildlife conservation and both animal and human
      health. Ribosomal and mitochondrial DNA sequences of parasites are useful to
      determine genetic diversity and to describe their likely dynamic evolution. In
      this study, we described the genetic diversity of S. scabiei individuals
      collected from wild animals in China by sequencing the ribosomal ITS-2 and
      mitochondrial 16S rRNA genes. A total of 13 Sarcoptes isolates of wildlife,
      coupled with one of rabbit origin, were subjected to genetic characteristics.
      After cloning and sequencing, 14 ITS-2 sequences and 12 16S rRNA sequences were
      obtained and analyzed. Further analysis of haplotype network and population
      genetic structure revealed that there were 79 haplotypes in ITS-2 (main haplotype
      H2) and 31 haplotypes in 16S rRNA (main haplotype C10). The phylogenetic trees
      showed some partial clustering by location and host, and the analysis of gene
      polymorphism may prompt that all isolates of S. scabiei have a similar origin. We
      speculate that the genetic evolution of S. scabiei may be related with that of
      the hosts, but more research is necessary to better understand the host-parasite
      co-evolutionary relationship in S. scabiei. These results provide new insights
      into understanding the population genetics and evolutionary biology of S. scabiei
      and therefore a better understanding of controlling its infestation pathways
      worldwide.

PMID- 30238309
TI  - Repeated Vowel Production Affects Features of Neural Activity in Sensorimotor
      Cortex.
AB  - The sensorimotor cortex is responsible for the generation of movements and
      interest in the ability to use this area for decoding speech by brain-computer
      interfaces has increased recently. Speech decoding is challenging however, since
      the relationship between neural activity and motor actions is not completely
      understood. Non-linearity between neural activity and movement has been found for
      instance for simple finger movements. Despite equal motor output, neural activity
      amplitudes are affected by preceding movements and the time between movements. It
      is unknown if neural activity is also affected by preceding motor actions during
      speech. We addressed this issue, using electrocorticographic high frequency band
      (HFB; 75-135 Hz) power changes in the sensorimotor cortex during discrete vowel
      generation. Three subjects with temporarily implanted electrode grids produced
      the /i/ vowel at repetition rates of 1, 1.33 and 1.66 Hz. For every repetition,
      the HFB power amplitude was determined. During the first utterance, most
      electrodes showed a large HFB power peak, which decreased for subsequent
      utterances. This result could not be explained by differences in performance.
      With increasing duration between utterances, more electrodes showed an equal
      response to all repetitions, suggesting that the duration between vowel
      productions influences the effect of previous productions on sensorimotor cortex
      activity. Our findings correspond with previous studies for finger movements and
      bear relevance for the development of brain-computer interfaces that employ
      speech decoding based on brain signals, in that past utterances will need to be
      taken into account for these systems to work accurately.

PMID- 30238311
TI  - Greater palatine canal injections reduce operative bleeding during endoscopic
      sinus surgery: a systematic review and meta-analysis.
AB  - OBJECTIVES: The use of greater palatine canal (GPC) injections of a local
      anesthetic and a vasoconstrictor to decrease surgical bleeding during endoscopic
      sinus surgery (ESS) is controversial. We investigated the role of a preoperative
      GPC injection to minimize intraoperative bleeding during ESS in patients with
      chronic sinusitis through a meta-analysis of the relevant literature. DATA
      SOURCES: PubMed, SCOPUS, and the Cochrane database. REVIEW METHODS: We screened
      the relevant literature published before May of 2018. Five articles that compared
      the pre-operative GPC injection (treatment group) with a placebo or no treatment
      (control group) were included for this analysis of the outcomes, which included
      an endoscopic grade of nasal bleeding and intraoperative hemodynamic stability
      during ESS. RESULTS: The endoscopic grade in the treatment group was
      significantly reduced when compared with the control group. No significant
      adverse effects were reported in the enrolled studies. The subgroup analyses of
      these results compared the concentrations of adrenalin (1:80,000 or 1:100,000),
      and adrenalin 1:80,000 showed significant effects on intraoperative bleeding when
      compared to adrenalin 1:100,000. CONCLUSION: This study demonstrated that GPC
      injections of local anesthesia with 1:80,000 adrenaline for ESS effectively
      reduced intraoperative bleeding. Additionally, this procedure showed no
      significant adverse effects, such as hemodynamic instability. However, the
      standardized dosing needs further investigation and more trials. LEVEL OF
      EVIDENCE: Ia.

PMID- 30238310
TI  - Preoperative diagnostic of parotid gland neoplasms: fine-needle aspiration
      cytology or core needle biopsy?
AB  - A preoperative cytologic or histologic diagnosis of parotid gland neoplasms is
      mandatory to decide which surgical procedure would be appropriate. Open biopsies
      are contraindicated because of the risk of recurrence secondary to tumour cell
      seeding; furthermore a subsequent curative parotid surgery can be complicated by
      a previous open biopsy. While fine-needle aspiration cytology (FNAC) was the only
      preoperative diagnostic procedure to distinguish benign versus malignant
      neoplasms over the past decades, core needle biopsy (CNB) has been increasingly
      used over the last few years. This created a debate as to whether FNAC or CNB
      should be the preoperative procedure of choice. The focus of this editorial is to
      analyse the advantages and disadvantages of FNAC and CNB, and to discuss which
      procedure is more appropriate in the preoperative work-up of parotid neoplasms.

PMID- 30238312
TI  - The Ammonium Channel NOD26 is the Evolutionary Innovation that Drives the
      Emergence, Consolidation, and Dissemination of Nitrogen-Fixing Symbiosis in
      Angiosperms.
AB  - Increasing evidence indicates that N-fixing symbiosis has evolved several times
      in the N-fixing clade of angiosperms and that this evolution is driven by a
      single evolutionary innovation. However, the genetics of this ancestral
      predisposition to N-fixing symbiosis remains unclear. A natural candidate for
      such molecular innovation is the ammonium channel NOD26, the main protein
      component of the symbiosome membrane, which facilitates the plant uptake of the
      nitrogen fixed by symbiotic bacteria. Here, in concordance with the emergence of
      N-fixing symbiosis in angiosperms but not in ancestral plants, phylogenetic
      analysis showed that NOD26 belongs to an angiosperm-exclusive subgroup of
      aquaporins. Integrated genomic, phylogenetic, and gene expression analyses
      supported NOD26 occurrence in the N-fixing clade, the increase in the NOD26 copy
      number by block and tandem duplications in legumes, and the low-copy number or
      even the loss of NOD26 in non-legume species of the N-fixing clade, which
      correlated with the possibility to lose N-fixing symbiosis in legume and non
      legume lineages. Metabolic reconstructions showed that retention of NOD26 in N
      fixing precursor could represent an adaptive mechanism to bypass energy crisis
      during anaerobic stress by ammonium detoxification. Finally, we discuss the
      potential use of NOD26 to transfer N-fixation to non-N-fixing crops as cereals.

PMID- 30238313
TI  - Detection and prevalence of adenoviruses from free-ranging black howler monkeys
      (Alouatta pigra).
AB  - Adenoviruses are important pathogens known to infect vertebrate hosts, including
      a wide range of primates. Despite its importance, data on the diversity of these
      viruses in non-human primates living in their natural habitat remain scarce. In
      this study, we conducted a surveillance of adenoviral infection in wild black
      howler monkeys from two protected natural areas in Mexico. This was achieved by
      analyzing 67 fecal samples using a nested PCR that targets the adenovirus DNA
      polymerase gene. Adenoviral DNA was detected in 12 samples from both study sites,
      with an overall prevalence of 17.9%. The amplified DNA sequences shared 100%
      nucleotide identity and phylogenetic analyses revealed that the haplotype
      detected was novel, and clustered with Platyrrhini mastadenovirus A, which was
      previously described in captive New World monkeys. Our data, along with the
      previous evidence, confirm that monkeys native to the Americas are the original
      hosts of these adenoviruses.

PMID- 30238314
TI  - Substitution of poultry and red meat with fish and the risk of peripheral
      arterial disease: a Danish cohort study.
AB  - PURPOSE: The aims of this study were to examine associations between
      substitutions of poultry and red meat intake with fish (total, lean or fatty) and
      the risk of peripheral arterial disease (PAD). We hypothesised that a higher
      intake of fish and a concomitant lower intake of poultry or red meat were
      associated with a lower risk of incident PAD. METHODS: We used data from a Danish
      cohort where middle-aged participants filled in food frequency and lifestyle
      questionnaires at baseline. During follow-up, we identified participants with
      valid diagnoses of PAD and analysed data by multivariable Cox regression
      analyses. Substitutions of 150 g/week of either poultry, red meat (processed or
      unprocessed) with 150 g/week of fish (total, lean or fatty) were explored.
      RESULTS: We followed the cohort (n = 54,597) for a median of 13.6 years and
      identified 897 cases with PAD. We found modest lower rates of PAD when intake of
      fish replaced a concomitant lower intake of unprocessed (HR 0.94, 95% CI 0.88
      1.01) and processed red meat (HR 0.94, 95% CI 0.87-1.02). Replacing unprocessed
      (HR 0.89, 95% CI 0.79-1.00) or processed red meat (HR 0.88, 95% CI 0.78-1.01)
      with fatty fish was associated with lower rates of PAD. No associations were
      observed when fish intake replaced poultry or when lean fish replaced red meat.
      CONCLUSIONS: This study suggests that substituting red meat with fish and
      especially fatty fish may be associated with a lower risk of PAD, although not
      statistically significant. Replacing poultry with fish was not associated with
      the risk of PAD.

PMID- 30238315
TI  - Effects of products designed to modulate the gut microbiota on hyperlipidaemia.
AB  - PURPOSE: Fatalities due to heart and cerebrovascular diseases caused by
      uncontrolled hyperlipidaemia increase every year; on the other hand, lipid
      lowering drugs are known to cause side effects. The gut microbiota has been
      thoroughly investigated by researchers and consumers, because they have unique
      functional properties and littler side effects. However, the effects of the gut
      microbiota remain controversial. We conducted a meta-analysis to assess the
      effects of products designed to modulate the gut microbiota on various
      hyperlipidaemias. METHODS: We systematically searched PubMed, Embase, Cochrane
      Library (Central), and Web of Science for randomized controlled trials (published
      before June 2017, and those only in English) to compare treatment (products
      designed to modulate the gut microbiota) versus placebo. Our main endpoints were
      total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol
      (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in serum. We assessed
      pooled data using a fixed effects model. RESULTS: Of 1337 identified studies, 21
      were eligible and included in our analysis (n = 1436 participants). The combined
      estimate of effect size for the impact of products designed to modulate the gut
      microbiota on serum TC (WMD - 11.07 mg/dL, 95% CI - 13.72 to - 8.43, p < 0.001),
      LDL-C (WMD - 10.96 mg/dL, 95% CI - 13.37 to - 8.56, p < 0.001), and HDL-C (WMD
      0.72 mg/dL, 95% CI 0.06-1.38, p = 0.032) were statistically significant, while no
      significant effect was found on TG concentrations (WMD - 0.56 mg/dL, 95% CI -
      5.59 to 4.47, p = 0.828). Subgroup analysis showed parallel trials, probiotics,
      and long-term intervention had better effects on lowering blood lipid levels.
      CONCLUSION: Products designed to modulate the gut microbiota results in changes
      of the plasma lipid concentrations and these changes may protect against
      cardiovascular disease.

PMID- 30238316
TI  - Relationship of dietary nitrate intake from vegetables with cardiovascular
      disease mortality: a prospective study in a cohort of older Australians.
AB  - PURPOSE: Short-term trials indicate inorganic nitrate and nitrate-rich vegetables
      may have vascular health benefits. However, few observational studies have
      explored the relationship between nitrate intake and long-term cardiovascular
      disease (CVD) outcomes. The primary aim of this study was to investigate the
      association of nitrate intake from vegetables with CVD mortality in a sample of
      older Australians. METHODS: A subgroup of participants without diabetes or major
      CVD at baseline (1992-1994) were included from the Blue Mountains Eye Study, a
      population-based cohort study of men and women aged >= 49 years. Diets were
      evaluated using a validated food frequency questionnaire at baseline, 5 years and
      10 years of follow-up. Vegetable nitrate intake was estimated using a
      comprehensive vegetable nitrate database. Cox proportional hazard regression was
      used to explore the association between vegetable nitrate intake and CVD
      mortality. RESULTS: During 14 years of follow-up, 188/2229 (8.4%) participants
      died from CVD. In multivariable-adjusted analysis, participants in quartile 2
      [69.5-99.6 mg/day; HR 0.53 (95% CI 0.35, 0.82)], quartile 3 [99.7-137.8 mg/day;
      HR 0.51 (95% CI 0.32, 0.80)], and quartile 4 [> 137.8 mg/day; HR 0.63 (95% CI
      0.41, 0.95)] of vegetable nitrate intake had lower hazards for CVD mortality
      compared to participants in quartile 1 (< 69.5 mg/day). CONCLUSIONS: In older
      Australian men and women, vegetable nitrate intake was inversely associated with
      CVD mortality, independent of lifestyle and cardiovascular risk factors. These
      findings confirm a recent report that intake of vegetable nitrate lowers the risk
      of CVD mortality in older women and extend these findings to older men.

PMID- 30238317
TI  - A new design of electronic control unit involving microcontroller to determine
      important parameters for target species in forest.
AB  - Forests, a valuable source provided by nature to living beings, are indispensable
      for many living organisms; hence, it is important to ensure the sustainability of
      forests. Determining the factors that exposure threats to the forests, executing
      protective methods against them and putting these methods into practise are
      important for the ecological cycle. Bark beetles, which have destructive effects
      on the ecosystem, are one of the factors that expose a threat to forests.
      Therefore, monitoring of these species and determination of effective control
      strategies are increasingly gaining importance in forestry. Conventional
      pheromone traps, which are being currently used, provide limited information on
      flight times of target species. Therefore, the technological development of the
      capture systems of these traps will determine future control trends. Hence,
      pheromone traps with electronic control unit were prepared in earlier (?1) and
      new designed (?2) versions. In ?2, 97.5% of target species were counted, and
      instant temperature, humidity and time parameters at the time of capture were
      recorded at a practiced field work for the system. In addition to the instant
      parameters recorded in ?2, an anemometer used for measuring wind speed, which is
      considered to have influence on the behaviour of target species, was incorporated
      into the system. In the trials, the counting success rates under daylight and
      darkness conditions for Ips sexdentatus adults were 98.1 and 97%, whereas the
      counting success rates for Pityocteines curvidens adults, which are smaller in
      size, were 96 and 99%, respectively. In conclusion, data obtained by recording
      the amount of target species along with the capture moment and parameters related
      to this will be very useful and provide determinative in the management of target
      species.

PMID- 30238318
TI  - Metformin for Weight Gain Associated with Second-Generation Antipsychotics in
      Children and Adolescents: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Weight gain is a potentially concerning side effect of second
      generation antipsychotics (SGAs). Metformin, a biguanide with antihyperglycemic
      effects, is used to manage weight gain in adults treated with SGAs. OBJECTIVE:
      The objective of this study was to perform the first systematic review and meta
      analysis of randomized controlled trials (RCTs) assessing the effects of
      metformin on weight gain in children and adolescents treated with SGAs. METHODS:
      Based on a pre-registered protocol (PROSPERO-CRD42017074839), we searched the
      PubMed, EMBASE, PsychoINFO, BIOSIS, Science Direct, Cochrane Central, and
      ClinicalTrials.gov electronic databases through March 2018 (with no restrictions
      on language, date, or type of publication) for RCTs that assessed the effect of
      metformin or placebo on body weight in children or adolescents (< 18 years of
      age) treated with selected SGAs (risperidone, aripiprazole, olanzapine, and
      clozapine) for any psychiatric disorder. We also contacted relevant drug
      manufacturers for possible additional pertinent studies/data. A random effects
      model was used and the quality of the included RCTs was assessed using the
      Cochrane Risk of Bias tool. RESULTS: Five RCTs (205 participants in total) were
      included in the meta-analysis. We found a significant weight decrease in the
      metformin group compared with placebo after 4, 12, and 16 weeks of treatment
      {mean difference - 0.98 kg (95% confidence interval [CI] - 1.26, - 0.69); - 1.83
      kg (95% CI - 2.47, - 1.18); and - 3.23 kg (95% CI - 5.59, - 0.86), respectively}.
      A weight decrease at weeks 2 and 8 did not reach statistical significance. The
      decrease in body mass index (BMI) paralleled that of weight, with a significant
      effect at weeks 4, 12, and 16. Overall, four studies were rated as unclear, and
      one study was rated as high, risk of bias. CONCLUSION: Meta-analytical evidence
      shows that metformin might decrease weight in children/adolescents treated with
      SGAs but additional high-quality evidence is needed. Clinicians need to be aware
      that this use of metformin is currently off-label.

PMID- 30238320
TI  - Role Differences in Healthcare: Overcoming Borders through Semiotic Skin is the
      Basis for Communication.
AB  - Role differences in healthcare systems are the very foundation of communication
      in this specific field of environment. It has to be understood as a collective
      corporation between collective individuals and thus connect through intertwined
      border zones. These border zones between collective communicators holds the
      notions of individuality, which is represented in the ability to decipher and
      negotiate the multiple layers in the communicative border zone. These processes
      in border zones of persons - in relation with others - are dealt with by the
      Semiotic Skin Theory. In addition, the biological skin is central for human lives
      and the Semiotic Skin is conceptualized as a socio-somatic-semiotic, layered and
      dynamic membrane that operates as a semi-permeable, communicative boundary. A
      constant interpretation between a self-reflecting system and an unending spiral
      of semiosis is the emergent of the semiotic skin. It creates a semi-permeable
      barrier that holds the very notions of the multi-layered skin-on-the-skin that is
      reflected in an embodied communication between humans and environment. In this
      theoretical understanding of an embodied aspect of not only meaning-making but
      also the regulative aspect of embodied interaction with others, the very idea of
      borders of individuality becomes the notion of interpretation. Any communication
      in a medical setting involves actions on the border of mutual understanding -
      e.g. communication between a pediatrician and a child. The concepts of a
      collective patient and a collective doctor are introduced as to understand the
      aspects of the multiple dynamics of the semiotic skin as the holder of an
      individual's personal ideas/interpretations in the interaction with one other
      person, holding multiple aspects from others as well. Examples of the interaction
      between patients and the healthcare system in Denmark illustrate how a new
      theoretical and practical performance of mastering the communicative partnership
      in the cross field between the healthcare system and psychology is born.

PMID- 30238319
TI  - Birth and death of Mx genes and the presence/absence of genes regulating Mx
      transcription are correlated with the diversity of anti-pathogenicity in
      vertebrate species.
AB  - Gene duplication and amino acid substitution are two types of genetic innovations
      of antiviral genes in inhibiting the emerging pathogens in different species. Mx
      proteins are well known for inhibiting negative-stranded RNA viruses and have
      evolved a number of paralogs or orthologs, showing distinct antiviral activities
      or capacities within or between species. The presence of upstream genes in the
      signaling pathway(s) that activates Mx genes (upstream regulators of Mx gene)
      also exhibits variety across species. The association between the evolution of Mx
      gene and their upstream regulators and the various antiviral capacities in host
      species has not been investigated. Herein, we traced the evolution of Mx gene and
      profiled the gene birth/death events on each branch of the 64 chordate species.
      We provided additional support that the diversity in gene member and amino acid
      changes in the different clades is correlated to their various antiviral
      activities of the species. We identified amino acid substitutions that may lead
      to the functional divergence between Mx paralogs in rodents. Although the copy
      number of the Mx gene is conserved in birds, infection by influenza A virus (IAV)
      results in diverse morbidity rates in different avian species. The evidences of
      gene interaction in the IAV-induced pathway and the genome analysis performed in
      this study indicated that the existence of the upstream regulators of Mx gene
      exhibits variation among different species, particularly in birds. The variation
      is related to the differences in the expression of Mx genes, resulting in the
      antiviral specificity and morbidity rates in avian species. We conclude that the
      antiviral capacity in host species is associated with the variations in the gene
      number of the Mx gene family and the existence of upstream regulators of Mx gene
      as well.

PMID- 30238321
TI  - Impact of Climate Change on Pollen and Respiratory Disease.
AB  - PURPOSE OF REVIEW: A warming world will impact everyone and everything. The
      practice of allergic and respiratory disease will not be excepted. All the
      impacts will be impossible to anticipate. This review is intended to discuss
      significant factors related to individuals with allergic and respiratory disease.
      RECENT FINDINGS: Recent findings include the increased growth of allergenic
      plants in response to higher carbon dioxide levels and warmer temperatures. This
      also contributes to the increased production of pollen as well as the appearance
      of allergenic species in new climactic areas. Stinging insects will extend their
      ranges into northern areas where they have not previously been a problem. The
      shift and extension of pollen seasons with warmer springs and later frosts have
      already been observed. Recent severe hurricanes and flooding events may be just
      the harbinger of increasing damp housing exposure related to sea level rise.
      Evidence is accumulating that indicates the expected higher number of ozone alert
      days and increased pollution in populated areas is bringing increases in pollen
      potency. Finally, increased exposure to smoke and particles from wild fires,
      resulting from heat waves, will contribute to the general increase in respiratory
      disease. The practice of allergy being closely aligned with environmental
      conditions will be especially impacted. Allergists should consider increasing
      educational activities aimed at making patients more aware of air quality
      conditions.

PMID- 30238322
TI  - Graphitic carbon nitride quantum dots as an "off-on" fluorescent switch for
      determination of mercury(II) and sulfide.
AB  - A rapid method has been developed for the determination of Hg(II) and sulfide by
      using graphitic carbon nitride quantum dots (g-CNQDs) as a fluorescent probe. The
      interaction between Hg(II) and g-CNQDs leads to the quenching of the blue g-CNQD
      fluorescence (with excitation/emission peaks at 390/450 nm). However, the
      fluorescence can be recovered after addition of sulfide such that the "turn-off"
      state is switched back to the "turn-on" state. The g-CNQDs were fully
      characterized by transmission electron microscopy, X-ray diffractometry, X-ray
      photoelectron spectroscopy, Fourier transform infrared spectroscopy, UV-vis
      absorption and fluorescence spectroscopy. Under the optimal experimental
      conditions, this probe is highly selective and sensitive to Hg(II). The linear
      response to Hg(II) extends from 0.20 to 21 MUM with a detection limit of 3.3 nM.
      In addition, sulfide can be detected via the recovery of fluorescence. The linear
      response range for sulfide species is from 8.0 to 45 MUM with a detection limit
      of 22 nM. The mechanism of the "turn-off-on" scheme is discussed. The methods
      have been applied to the analysis of spiked tap water, lake water and wastewater
      samples. Graphical abstract Schematic of an off-on fluorescent probe for
      mercury(II). The fluorescence of graphitic carbon nitride quantum dots (g-CNQDs)
      is quenched by Hg2+ but is recovered after reacting with S2- as it can combine
      with Hg2+ on the surface of g-CNQDs.

PMID- 30238324
TI  - Consumption of ultra-processed foods and obesity in Canada.
AB  - OBJECTIVES: To assess the association between consumption of ultra-processed
      foods and obesity in the Canadian population. METHODS: Cross-sectional study
      including 19,363 adults aged 18 years or more from the 2004 Canadian Community
      Health Survey, cycle 2.2. Ultra-processed food intake was estimated using daily
      relative energy intake of ultra-processed food (% of total energy intake) from
      data obtained by 24-h food recalls. Obesity was assessed using body mass index
      (BMI >= 30 kg/m2). Univariate and multivariate linear regressions were performed
      to describe ultra-processed food consumption according to socio-economic and
      demographic variables, and multivariate logistic regression was performed to
      verify the association between ultra-processed food consumption and obesity,
      adjusting for potential confounders, including socio-demographic factors,
      physical activity, smoking, immigrant status, residential location, and measured
      vs self-reported weight and height. RESULTS: Ultra-processed foods make up almost
      half (45%) of the daily calories consumed by Canadian adults. Consumption of
      these foods is higher among men, younger adults, those with fewer years of formal
      education, smokers, those physically inactive, and Canadian-born individuals.
      Ultra-processed food consumption is positively associated with obesity. After
      adjusting for confounding factors, individuals in the highest quintile of ultra
      processed food consumption were 32% more likely of having obesity compared to
      individuals in the first quintile (predicted OR = e0.005 * 56 = 1.32; 95% CI =
      1.05-1.57). CONCLUSION: Canadians would benefit from reducing consumption of
      ultra-processed foods and beverages and increasing consumption of freshly
      prepared dishes made from unprocessed or minimally processed foods.

PMID- 30238325
TI  - Detectable levels of eHSP72 in plasma are associated with physical activity and
      antioxidant enzyme activity levels in hypertensive subjects.
AB  - Previous studies reported that extracellular HSP72 (eHSP72) correlates with poor
      prognosis, markers of vascular dysfunction, and the severity of cardiovascular
      diseases, associated with a systemic oxidative and inflammatory profile. On the
      other hand, eHSP72 may represent immune-regulatory signaling that is related to
      exercise benefits, but the association between physical activity levels and
      eHSP72 levels is not established. Thus, since regular physical activity may avoid
      oxidative stress and inflammation, we investigate whether detectable levels of
      eHSP72 in plasma are associated with physical activity and antioxidant enzyme
      activity levels in hypertensive subjects. Physical activity levels of
      hypertensive subjects (n = 140) were measured by tri-axial movement sensor
      pedometer for 24 h during 5 consecutive days. One day after, blood was collected
      into heparinized tubes for oxidative stress analyses (catalase-CAT and superoxide
      dismutase-SOD activities and malondialdehyde levels) or in disodium EDTA tubes
      for eHSP72 assays. Thus, hypertensive subjects were classified as physically
      inactive (< 10,000 footsteps/day) or active (> than 10,000 footsteps/day) and
      according detectable or not detectable eHSP72 levels in plasma, performing the
      inactive/eHSP72-, active/eHSP72-, inactive/eHSP72+, and active/eHSP72+ groups. We
      found that detectable levels of eHSP72 in plasma were associated with physical
      activity levels and low oxidative stress profile (Higher CAT and SOD activities
      and low malondialdehyde levels). eHSP72 levels can be used as a biomarker of the
      amount of physical activity necessary to improve antioxidant defense and thus
      cardiovascular health in hypertensive subjects.

PMID- 30238326
TI  - Cabergoline for the treatment of bromocriptine-resistant invasive giant
      prolactinomas.
AB  - PURPOSE: Few studies have specifically focused on the effect of cabergoline on
      invasive giant prolactinomas (IGPs) resistant to bromocriptine. This study aims
      to evaluate whether cabergoline could be used as an effective therapy for
      patients with bromocriptine-resistant IGPs. METHODS: This retrospective study
      included 15 patients with bromocriptine-resistant IGPs who received treatment at
      our department during 2007-2015. Cabergoline was administered in all 15 patients,
      with the dose adjusted depending on the prolactin response of each patient.
      Parameters for outcome assessment included prolactin level, pituitary function,
      tumor size, improvement of the clinical symptoms, visual field defects, drug
      tolerance, and disease recurrence. RESULTS: Cabergoline was effective for the
      treatment of the patients with bromocriptine -resistant IGPs as represented by
      normalization of the prolactin level in 12/15 patients; improvement or
      normalization of the pituitary function in 4/5 patients with hypopituitarism;
      significant reduction in tumor size in 14/15 patients; and relief of the clinical
      symptoms in 11/15 patients. All 15 patients showed good tolerance to cabergoline.
      In addition, no recurrence was observed during the mean follow-up period of 63.47
      (range 30-145) months. CONCLUSIONS: Data of this retrospective study demonstrate
      that cabergoline is an excellent option for the treatment of patients with
      bromocriptine-resistant IGPs.

PMID- 30238327
TI  - Surgical outcomes and predictors of glucose metabolism alterations for growth
      hormone-secreting pituitary adenomas: a hospital-based study of 151 cases.
AB  - PURPOSE: The surgical outcome on glucose metabolism in acromegaly patients is not
      fully understood. We aimed to investigate the impact of surgery on glucose
      metabolism and identify key factors that influence alterations of glucose
      metabolic status in acromegaly patients. METHODS: Oral glucose tolerance test was
      performed in 151 newly diagnosed acromegaly patients before and 3-12 months after
      surgery. Insulin resistance and insulin secretion was assessed. Patients were
      grouped as cured, discordant, and having active disease according to
      postoperative growth hormone (GH) and insulin-like growth factor-1 (IGF-1)
      levels. Receiver-operating characteristic curves were generated to determine the
      optimal cut-off points to predict the impact of surgery on glucose metabolism.
      RESULTS: At baseline, 32.5%, 41.7%, and 25.8% patients were categorized as having
      normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes
      mellitus (DM), respectively. After surgery, improved glucose tolerance was
      observed in 87.3% patients with IGT and 66.7% patients with DM. Deterioration was
      observed in 14.3% patients with NGT. Glucose tolerance improved in patients with
      lower preoperative FBG, 2 h-BG, and HbA1c and higher HOMA-beta and IGI/IR. The
      proportion of NGT was significantly increased in surgically cured patients (28.3%
      vs. 79.2%, P < 0.001) and those with normal GH but elevated IGF-1 levels (25.6%
      vs. 79.5%, P < 0.001), but not in patients with active disease (42.9% vs. 57.1%,
      P = 0.131). Baseline FBG < 6.35 mmol/l predicted improved glucose metabolism
      after surgery. CONCLUSIONS: Glucose metabolic status improved in patients with
      preserved beta-cell function. Preoperative FBG was an independent predictor for
      improved glucose tolerance status after surgery.

PMID- 30238328
TI  - The relationship between anti-Mullerian hormone serum level and body mass index
      in a large cohort of infertile patients.
AB  - PURPOSE: To evaluate the relationship between serum Anti-Mullerian hormone (AMH)
      level and body mass index (BMI) in infertile patients. METHODS: Medical records
      of patients with infertility evaluated between January 2013 and February 2018 in
      the Reproductive Medicine Department of a private hospital were reviewed.
      Patients with the following criteria were excluded from the study: polycystic
      ovary syndrome, primary ovarian insufficiency, AMH values > 10 ng/mL, current
      oral contraceptive users and previous ovarian surgery or endometriosis, and
      anovulation of other causes, except decreased ovarian reserve. RESULTS: A total
      of 2204 infertile patients were included (mean age 34.58 +/- 4.3 years, mean BMI
      22.35 +/- 3.6 kg/m2, and mean serum AMH 2.44 +/- 2.17 ng/ml). In the entire group
      of patients, serum AMH level was positively correlated with BMI after adjustment
      for age (beta = 0.059, p < 0.005). When the association between serum AMH level
      and BMI was analysed in subgroups of patients, after adjustment for age, we found
      a positive correlation between the two parameters in patients <= 35 years old (<
      0.05), of normal weight (p < 0.05) and with normal ovarian reserve (p < 0.05).
      After adjustment for age, BMI >= 25 kg/m2 was significantly associated with
      higher AMH values in comparison to normal weight patients. CONCLUSIONS: In
      infertile patients, AMH is positively correlated with BMI, especially in patients
      younger than 35 years, of normal weight and with normal ovarian reserve.
      Moreover, the presence of mild excess adiposity seems to be associated with
      higher AMH values. Our data contradict the previous studies showing a negative
      impact of excess adiposity on AMH serum levels.

PMID- 30238329
TI  - Surgical management of oral submucous fibrosis using buccal fat pad: a
      retrospective study of 30 cases.
AB  - The aim of our study was to evaluate the effectiveness of buccal fat pad (BFP) in
      the management of oral submucous fibrosis (OSMF). Retrospective records of 30
      patients of OSMF treated with BFP with atleast a year of follow-up were analyzed.
      Patients were divided into groups based on the stages of OSMF. Surgical
      management consisted of resection of fibrous bands, bilateral temporalis myotomy,
      and coronoidectomy followed by grafting with BFP. There were 17 patients of stage
      III (mouth opening 16-25 mm) and 13 patients of stage IV OSMF (mouth opening less
      than 16 mm). The mean mouth opening of stage III group pre-operatively was 19.94
      +/- 2.19 mm which increased to a mean of 35.12 +/- 5.69 mm (p < 0.0001). For
      patients with stage IV OSMF, the mouth opening increased from a pre-operative of
      10.23 +/- 4.07 mm to a post-operative of 31.46 +/- 6.78 mm (p < 0.0001). No intra
      operative complications were noted in any patient. Relapse was seen in 1 patient
      (5.8%) of stage III while 3 patients (23.07%) had relapse in stage IV group. Our
      results indicate that BFP is a good flap owing to its benefits which are easy to
      harvest and entails minimal morbidity for management of OSMF.

PMID- 30238331
TI  - CIRSE 2018.

PMID- 30238332
TI  - The Relationship Between Gelatin Sponge Preparation Methods and the Incidence of
      Intrauterine Synechia Following Uterine Artery Embolization for Postpartum
      Hemorrhage.
AB  - PURPOSE: To evaluate the relationship between gelatin sponge preparation methods
      and the incidence of intrauterine synechia following uterine artery embolization
      (UAE) for postpartum hemorrhage (PPH). MATERIALS AND METHODS: In a retrospective
      monocentric study, we used data from 20 consecutive UAE procedures (19 patients)
      for PPH, performed in 2007-2016, in which gelatin sponge had been used. The
      gelatin sponge was processed either into a slurry by pumping it back and forth
      about 10 times through two syringes connected to a three-way stopcock or into
      pledgets using a scalpel and small scissors to obtain pieces approximately 2 * 2
      * 2 mm in size. Patient information was obtained from medical records, and the
      data were compared between patients treated with the slurry (n = 7) or pledgets
      (n = 13) forms. Due to the lack of follow-up data and hysterectomy after UAE, the
      sample size was 6 and 12 because 1 patient with 2 procedures was excluded.
      RESULTS: The rate of intrauterine synechia was significantly higher in the slurry
      group (5/6, 83.3%) than that in the pledgets group (0/12, 0%; P < 0.001). In
      contrast, there were no significant differences in population characteristics,
      such as the incidence of placenta accreta, non-placental diseases, and severity
      of shock (DIC score, shock index, or blood loss) between the groups. CONCLUSIONS:
      Although non-randomization and small sample size were the two main limitations,
      our observations suggest that UAE using gelatin sponge slurry may be associated
      with a high incidence of intrauterine synechia compared to UAE using pledgets.

PMID- 30238330
TI  - Effectiveness of preanesthetic administration of gabapentin on sedative action
      during intravenous sedation with propofol.
AB  - PURPOSE: There are no sufficient evidences for the sedative effect of gabapentin
      during anesthesia, especially intravenous sedation (IVS). The purpose of this
      study was to evaluate the sedative effect of gabapentin as preanesthetic
      medication during the IVS with propofol. METHODS: 10 volunteer subjects joined
      this study. They underwent propofol IVS three times on separate days. On the
      first day, the IVS without gabapentin was performed as a control. On the second
      and the third day, gabapentin 200 mg and 400 mg were administered before the IVS,
      respectively. The target blood concentration (CT) of propofol was gradually
      increased, and the bispectral index (BIS) value and Ramsay sedation score (RSS)
      were evaluated at each propofol CT. Postanesthetic complications and influences
      on vital signs were also evaluated. RESULTS: Compared to the control group, the
      propofol CTs in the gabapentin 400 mg group significantly reduced at the BIS
      values of 60 and 70 (p = 0.031 and p = 0.043, respectively), and at RSS 3, 4, 5
      and 6 (p = 0.040, p = 0.004, p = 0.001 and p = 0.004, respectively). There was no
      significant difference in propofol CTs between the control group and the
      gabapentin 200 mg group. There were no abnormality and no deterioration in
      circulation and respiration in all groups. There were no significant increases in
      complications with the administration of gabapentin. CONCLUSION: The oral
      administration of 400 mg dose of gabapentin reduced the propofol CTs for
      achieving an adequate sedation level on IVS.

PMID- 30238333
TI  - Establishing a Platform for Interest and Education in Interventional Radiology
      Amongst Radiology Trainees.
AB  - PURPOSE: Over recent times, procedural Radiologists have begun to establish
      themselves as the distinct subspecialty of Interventional Radiology (IR). The
      Interventional Radiology Society of Australasia (IRSA) was established in 1982 to
      share collaborative ideas, encourage research, and promote education. IRSA
      developed a weekend registrar workshop attended by Radiology Registrars from
      Australia and New Zealand. In the 2018 event, we surveyed the Registrars to
      identify their interest in IR training before and after the workshop. MATERIALS
      AND METHODS: The event was held over a weekend and consisted of both lectures and
      hands-on workshops. A survey was handed to all 67 registrants of the workshop and
      there was a 55% response rate including 78% of females in attendance. RESULTS:
      Before the workshop, trainees rated their interest in IR training at a mean of
      3.7 out of 5. After the workshop, trainees rated their interest in IR training as
      an average of 4.4 out of 5 (p < 0.001). The difference in interest between males
      and females before the workshop (4.0 vs. 3.1) was significant (p = 0.003),
      however after the workshop (4.5 vs. 4.1) was not significant (p = 0.07). The
      change in interest from attending the workshop was significant between genders, p
      = 0.03 (male interest increased mean 0.5, female increased mean 1.0). CONCLUSION:
      We show that a program of lectures and workshops designed to generate interest in
      IR leads to a significant increase in training interest, particularly amongst
      females. Other subspecialty groups should consider this type of intervention and
      promote ongoing education and inspiration. LEVEL OF EVIDENCE: Cross-sectional
      study, Level IV.

PMID- 30238334
TI  - Preoperative Portal Vein Embolization Alone with Biliary Drainage Compared to a
      Combination of Simultaneous Portal Vein, Right Hepatic Vein Embolization and
      Biliary Drainage in Klatskin Tumor.
AB  - PURPOSE: To compare estimated future remnant liver (FRL) growth following portal
      vein embolization or liver venous deprivation (LVD) (combined PVE and right
      hepatic vein embolization), before surgery for a Klatskin tumor in patients who
      receive intraoperative biliary drainage or before venous interventional
      radiology. MATERIAL AND METHOD: Six patients underwent LVD and six underwent PVE
      alone before hepatectomy for a Klatskin tumor. Before embolization, the FRL
      ratio, prothrombin time and bilirubin levels were similar in both groups. The FRL
      was determined before and 3 weeks after embolization by enhanced CT. PVE was
      performed with n-butyl-2-cyanoacrylate, and the right hepatic vein was embolized
      with vascular plugs during the same procedure. Biliary drainage was performed
      percutaneously or by endoscopy. Post-hepatectomy liver function and duration of
      hospital stay were assessed. RESULTS: There were no adverse events. The median
      FRL ratio was significantly higher following LVD than after PVE 58% (54-71) and
      37% (30-44), respectively, p = 0.017. The FRL volume after embolization was 1.6
      times higher after LVD than PVE (p = 0.016). Four and five patients were operated
      in the LVD and PVE groups, respectively. There was a trend toward a shorter
      median postoperative hospital stay and 90-day mortality in the LVD versus PVE
      group: 14 versus 44 days, (p = 0.114) and 0 versus two deaths (p = 0.429),
      respectively. CONCLUSIONS: LVD associated with biliary drainage is safe and
      results in a better FRL ratio than biliary drainage associated with PVE alone.

PMID- 30238336
TI  - Two New Species of the Spittlebug Genus Ocoaxo Fennah (Hemiptera: Cercopidae)
      from Mexico, and Keys for the Groups, Group Three, and First Subgroup.
AB  - Insects of the family Cercopidae are known as spittlebugs or froghoppers and are
      represented by 62 genera in the Neotropical region. One of these genera is Ocoaxo
      Fennah, 1968 with 30 species. The most recent species to be accepted into this
      genus, Ocoaxo costaricanus, was described by Nast (Ann Zool 33:93-101, 1975).
      Herein, two new species of Ocoaxo from Mexico are described. One of these new
      species forms a complex together with Ocoaxo assimilis (Walker) and Ocoaxo
      varians (Stal). The complex has economic importance in the mountainous areas of
      the states of Puebla and Oaxaca because it attacks Pinus spp. and causes a
      disorder called "pine decline." Additionally, dichotomous keys were designed to
      identify the Ocoaxo Fennah groups and also the species of the subgroup bivittus.

PMID- 30238335
TI  - Genetic deficiency of the tumor suppressor protein p53 influences erythrocyte
      survival.
AB  - The transcription factor p53 suppresses tumor growth by inducing nucleated cell
      apoptosis and cycle arrest. Because of its influence on primitive erythroid cell
      differentiation and survival, p53 is an important determinant of erythropoiesis.
      However, the impact of p53 on the fate of erythrocytes, cells lacking nucleus and
      mitochondria, during their post-maturation phase in the circulation remained
      elusive. Erythrocyte survival may be compromised by suicidal erythrocyte death or
      eryptosis, which is hallmarked by phosphatidylserine translocation and stimulated
      by increase of cytosolic Ca2+ concentration. Here, we comparatively examined
      erythrocyte homeostasis in p53-mutant mice (Trp53tm1Tyj/J) and in corresponding
      WT mice (C57BL/6J) by analyzing eryptosis and erythropoiesis. To this end,
      spontaneous cell membrane phosphatidylserine exposure and cytosolic Ca2+
      concentration were higher in erythrocytes drawn from Trp53tm1Tyj/J mice than from
      WT mice. Eryptosis induced by glucose deprivation, a pathophysiological cell
      stressor, was slightly, but significantly more prominent in erythrocytes drawn
      from Trp53tm1Tyj/J mice as compared to WT mice. The loss of erythrocytes by
      eryptosis was fully compensated by enhanced erythropoiesis in Trp53tm1Tyj/J mice,
      as reflected by increased reticulocytosis and abundance of erythroid precursor
      cells in the bone marrow. Accordingly, erythrocyte number, packed cell volume and
      hemoglobin were similar in Trp53tm1Tyj/J and WT mice. Taken together, functional
      p53 deficiency enhances the turnover of circulating erythrocytes by parallel
      increase of eryptosis and stimulated compensatory erythropoiesis.

PMID- 30238337
TI  - Time course of differentiation of different cell types in 3D-reconstructed
      eccrine sweat glands.
AB  - Epidermal basal cells invaginate into the dermis to form sweat ducts, which then
      grow downwards further to form secretory coils during the ontogenesis of eccrine
      sweat glands, but the time course of differentiation of different cell types in
      3D-reconstructed eccrine sweat glands remain unclear. In this study, secretory
      cell-specific marker K7, clear secretory cell-specific marker CA II, dark
      secretory cell-specific marker GCDFP-15, myoepithelial cell-specific marker alpha
      SMA, inner duct cell-specific marker S100P and outer duct cell-specific marker
      S100A2 were detected by immunofluorescence staining. The results showed that
      S100P and S100A2 were first detected at 2 weeks post implantation, K7 and alpha
      SMA at 3 weeks, and GCDFP-15 and CA II at 4 weeks. The differentiation of ducts
      preceded secretory coils in 3D-reconstructed eccrine sweat glands. After 8 weeks
      post implantation, the distribution of these markers in 3D-reconstructed eccrine
      sweat glands was similar to that in native ones, and the percentage of the 3D
      reconstructed glands expressing these markers maintained steady. We conclude that
      although the 3D-reconstructed and native eccrine sweat glands originated from
      different cells, the differentiation of different cell types in 3D-reconstructed
      eccrine sweat glands parallels the sequence observed during embryonic
      development.

PMID- 30238338
TI  - Deinococcus terrigena sp. nov., a novel member of the family Deinococcaceae.
AB  - A bacterial strain, S13-1-2-1T, was isolated from a soil sample collected in
      Gyeongsangnam-do province, South Korea. Cells were observed to be Gram-stain
      negative, short rod-shaped and colonies to be pale pink in colour. Analysis of
      16S rRNA gene sequences identified this strain as a member of the genus
      Deinococcus in the family Deinococcaceae, with high levels of sequence similarity
      with Deinococcus ficus CC-FR2-10T (97.9%) and Deinococcus enclensis NIO-1023T
      (95.4%). Growth of strain S13-1-2-1T was observed at 10-42  degrees C, pH 6-8,
      and in the presence of 0-1.0% NaCl. The isolate was found to exhibit resistance
      to gamma radiation (D10 10.1 KGy) and UV-light (D10 612 J/m2). The major
      peptidoglycan amino acids were identified as D-glutamic acid, glycine, alanine
      and L-ornithine. The predominant respiratory quinone of the strain was identified
      as menaquinone-8, the major fatty acids were found to be C16:1 omega7c (31.4%),
      C16:0 (18.4%), and C17:1 omega8c (17.4%) and the major polar lipids were observed
      to be an unidentified phosphoglycolipid and an unidentified glycolipid. The
      genomic DNA G + C content of the strain was determined to be 69.2 mol%. DNA-DNA
      hybridization with D. ficus showed a relatedness value of 31.5 +/- 4.2%. The DNA
      DNA hybridization result and the differentiating phenotypic properties clearly
      indicate that strain S13-1-2-1T represents a novel species in the genus
      Deinococcus, for which the name Deinococcus terrigena sp. nov. is proposed. The
      type strain is S13-1-2-1T (= KCTC 33939T = JCM 32248T).

PMID- 30238339
TI  - Sphaerimonospora triticiradicis sp. nov., a novel actinomycete isolated from a
      root of wheat (Triticum aestivum L.).
AB  - A novel actinomycete, designated strain NEAU-HRGS1-10T, was isolated from a root
      of wheat (Triticum aestivum L.) collected from Zhumadian, Henan Province, Central
      China and characterised using a polyphasic approach. The organism was found to
      have morphological and chemotaxonomic characteristics typical of members of the
      genus Sphaerimonospora. The major menaquinones and the whole cell hydrolysates
      were identified as MK-9(H4) and MK-9(H2) and meso-diaminopimelic acid and
      madurose, respectively. The phospholipid profile was found to contain
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol,
      phosphatidylinositol mannosides, phosphatidylmonomethylethanolamine, a
      phosphoglycolipid, an unidentified lipid and an unidentified phospholipid. The
      major fatty acids were identified as iso-C16:0 and 10-methyl C17:0. The 16S rRNA
      gene sequence analysis showed that strain NEAU-HRGS1-10T is closely related to
      Sphaerimonospora mesophila JCM 3151T (99.0%), Sphaerimonospora cavernae NBRC
      111481T (97.9%) and Sphaerimonospora thailandensis NBRC 107569T (97.4%). However,
      DNA-DNA relatedness, cultural and physiological and biochemical data showed that
      strain NEAU-HRGS1-10T can be distinguished from its close relatives. Therefore,
      it is proposed that strain NEAU-HRGS1-10T represents a novel species of the genus
      Sphaerimonospora, for which the name Sphaerimonospora triticiradicis sp. nov. is
      proposed. The type stain is NEAU-HRGS1-10T (= CGMCC 4.7401T = DSM 104915T).

PMID- 30238340
TI  - Chronic oral methylphenidate treatment increases microglial activation in rats.
AB  - Methylphenidate (MP) is a widely prescribed psychostimulant used to treat
      attention deficit hyperactivity disorder. Previously, we established a drinking
      paradigm to deliver MP to rats at doses that result in pharmacokinetic profiles
      similar to treated patients. In the present study, adolescent male rats were
      assigned to one of three groups: control (water), low-dose MP (LD; 4/10 mg/kg),
      and high dose MP (HD; 30/60 mg/kg). Following 3 months of treatment, half of the
      rats in each group were euthanized, and the remaining rats received only water
      throughout a 1-month-long abstinence phase. In vitro autoradiography using [3H]
      PK 11195 was performed to measure microglial activation. HD MP rats showed
      increased [3H] PK 11195 binding compared to control rats in several cerebral
      cortical areas: primary somatosensory cortex including jaw (68.6%), upper lip
      (80.1%), barrel field (88.9%), and trunk (78%) regions, forelimb sensorimotor
      area (87.3%), secondary somatosensory cortex (72.5%), motor cortices 1 (73.2%)
      and 2 (69.3%), insular cortex (59.9%); as well as subcortical regions including
      the thalamus (62.9%), globus pallidus (79.4%) and substantia nigra (22.7%).
      Additionally, HD MP rats showed greater binding compared to LD MP rats in the
      hippocampus (60.6%), thalamus (59.6%), substantia nigra (38.5%), and motor 2
      cortex (55.3%). Following abstinence, HD MP rats showed no significant
      differences compared to water controls; however, LD MP rats showed increased
      binding in pre-limbic cortex (78.1%) and ventromedial caudate putamen (113.8%).
      These findings indicate that chronic MP results in widespread microglial
      activation immediately after treatment and following the cessation of treatment
      in some brain regions.

PMID- 30238341
TI  - Could hypoxia influence basic biological properties and ultrastructural features
      of adult canine mesenchymal stem /stromal cells?
AB  - The aim of the present study was to compare canine adipose tissue mesenchymal
      stem cells cultured under normoxic (20% O2) and not severe hypoxic (7% O2)
      conditions in terms of marker expression, proliferation rate, differentiation
      potential and cell morphology. Intra-abdominal fat tissue samples were recovered
      from 4 dogs and cells isolated from each sample were cultured under hypoxic and
      normoxic conditions. Proliferation rate and adhesion ability were determined,
      differentiation towards chondrogenic, osteogenic and adipogenic lineages was
      induced; the expression of CD44, CD34, DLA-DQA1, DLA-DRA1 was determined by PCR,
      while flow cytometry analysis for CD90, CD105, CD45 and CD14 was carried out. The
      morphological study was performed by transmission electron microscopy. Canine AT
      MSCs, cultured under different oxygen tensions, maintained their basic biological
      features. However, under hypoxia, cells were not able to form spheroid aggregates
      revealing a reduction of their adhesivness. In both conditions, MSCs mainly
      displayed the same ultrastructural morphology and retained the ability to produce
      membrane vesicles. Noteworthy, MSCs cultivated under hypoxya revealed a huge
      shedding of large complex vesicles, containing smaller round-shaped vesicles. In
      our study, hypoxia partially influences the basic biological properties and the
      ultrastructural features of canine mesenchymal stem /stromal cells. Further
      studies are needed to clarify how hypoxia affects EVs production in term of
      amount and content in order to understand its contribution in tissue regenerative
      mechanisms and the possible employment in clinical applications. The findings of
      the present work could be noteworthy for canine as well as for other mammalian
      species.

PMID- 30238342
TI  - Clinical heterogeneity of patients with stool samples testing PCR+/Tox- from a
      two-step Clostridium difficile diagnostic algorithm.
AB  - The clinical significance of indeterminate (PCR+/Tox-) results for patients
      tested with a two-step algorithm for Clostridium difficile infection (CDI) is
      uncertain. We aimed to evaluate the clinical presentation and 8-week outcomes of
      patients with indeterminate test results. Patients with stool samples testing
      positive by PCR and negative by toxin A/B immunoassay between February 1, 2017,
      and April 30, 2018, were assessed by antimicrobial stewardship program (ASP)
      clinicians and classified as colonized or infected. Retrospective chart review
      was performed to obtain outcomes occurring within 8 weeks of testing, including
      recurrent C. difficile diarrhea, subsequent treatment for CDI, follow-up C.
      difficile testing, all-cause mortality, and CDI-related complications. In total,
      110 PCR+/Tox- patients were evaluated. ASP classified 54% of patients as infected
      and 46% as colonized. Patients assessed and classified as colonized did not have
      increased adverse outcomes by 8 weeks compared to those assessed as infected,
      despite not receiving treatment for CDI. We conclude that PCR+/Tox- patients are
      heterogeneous with respect to clinical presentation. Negative toxin A/B
      immunoassay in a two-step algorithm should not be interpreted in isolation to
      distinguish colonization from infection as many PCR+/Tox- results may be
      clinically significant for CDI.

PMID- 30238343
TI  - Novel diagnostic ELISA test for discrimination between infections with Yersinia
      enterocolitica and Yersinia pseudotuberculosis.
AB  - Yersiniosis is a foodborne infection caused by Yersinia enterocolitica or
      Yersinia pseudotuberculosis. Although yersiniosis is most often self-limiting,
      some patients develop chronic infections, such as reactive arthritis,
      glomerulonephritis, or myocarditis, which require an antibiotic treatment.
      Whereas early infections can be diagnosed by direct detection of bacteria,
      chronic infections can only be identified by serological tests. At this point, a
      serological method for differentiation between infections with the two Yersinia
      species is important since antibiotic susceptibility of these bacteria is
      different. Traditional immunoassays do not distinguish between infections with Y.
      enterocolitica and Y. pseudotuberculosis. The only test that allows for this
      differentiation is Mikrogen's strip test where discrimination between the two
      types of infection is based on two recombinant bacterial proteins, MyfA and PsaA
      (specific for Y. enterocolitica and Y. pseudotuberculosis, respectively). Here,
      we show that Y. enterocolitica and Y. pseudotuberculosis, cultured under the
      conditions that mimic the natural rout of infection, express surface antigens
      different from MyfA and PsaA that can also be used in a discrimination test.
      Further, we describe a new ELISA that is based on the whole bacteria and
      recombinant MyfA and PsaA as antigens, and that allows the differentiation
      between infections with Y. enterocolitica and Y. pseudotuberculosis and
      simultaneous detection of yersiniosis.

PMID- 30238344
TI  - A Compressed-Sensing Based Blind Deconvolution Method for Image Deblurring in
      Dental Cone-Beam Computed Tomography.
AB  - In cone-beam computed tomography (CBCT), reconstructed images are inherently
      degraded, restricting its image performance, due mainly to imperfections in the
      imaging process resulting from detector resolution, noise, X-ray tube's focal
      spot, and reconstruction procedure as well. Thus, the recovery of CBCT images
      from their degraded version is essential for improving image quality. In this
      study, we investigated a compressed-sensing (CS)-based blind deconvolution method
      to solve the blurring problem in CBCT where both the image to be recovered and
      the blur kernel (or point-spread function) of the imaging system are
      simultaneously recursively identified. We implemented the proposed algorithm and
      performed a systematic simulation and experiment to demonstrate the feasibility
      of using the algorithm for image deblurring in dental CBCT. In the experiment, we
      used a commercially available dental CBCT system that consisted of an X-ray tube,
      which was operated at 90 kVp and 5 mA, and a CMOS flat-panel detector with a 200
      MUm pixel size. The image characteristics were quantitatively investigated in
      terms of the image intensity, the root-mean-square error, the contrast-to-noise
      ratio, and the noise power spectrum. The results indicate that our proposed
      method effectively reduced the image blur in dental CBCT, excluding repetitious
      measurement of the system's blur kernel.

PMID- 30238345
TI  - Restoration of Full Data from Sparse Data in Low-Dose Chest Digital Tomosynthesis
      Using Deep Convolutional Neural Networks.
AB  - Chest digital tomosynthesis (CDT) provides more limited image information
      required for diagnosis when compared to computed tomography. Moreover, the
      radiation dose received by patients is higher in CDT than in chest radiography.
      Thus, CDT has not been actively used in clinical practice. To increase the
      usefulness of CDT, the radiation dose should reduce to the level used in chest
      radiography. Given the trade-off between image quality and radiation dose in
      medical imaging, a strategy to generating high-quality images from limited data
      is need. We investigated a novel approach for acquiring low-dose CDT images based
      on learning-based algorithms, such as deep convolutional neural networks. We used
      both simulation and experimental imaging data and focused on restoring
      reconstructed images from sparse to full sampling data. We developed a deep
      learning model based on end-to-end image translation using U-net. We used 11 and
      81 CDT reconstructed input and output images, respectively, to develop the model.
      To measure the radiation dose of the proposed method, we investigated effective
      doses using Monte Carlo simulations. The proposed deep learning model effectively
      restored images with degraded quality due to lack of sampling data. Quantitative
      evaluation using structure similarity index measure (SSIM) confirmed that SSIM
      was increased by approximately 20% when using the proposed method. The effective
      dose required when using sparse sampling data was approximately 0.11 mSv, similar
      to that used in chest radiography (0.1 mSv) based on a report by the Radiation
      Society of North America. We investigated a new approach for reconstructing
      tomosynthesis images using sparse projection data. The model-based iterative
      reconstruction method has previously been used for conventional sparse sampling
      reconstruction. However, model-based computing requires high computational power,
      which limits fast three-dimensional image reconstruction and thus clinical
      applicability. We expect that the proposed learning-based reconstruction strategy
      will generate images with excellent quality quickly and thus have the potential
      for clinical use.

PMID- 30238346
TI  - 'Youth's Conflict Resolution Strategies in their Dating Relationships'.
AB  - Youth can experience conflicts with their dating partner and then need strategies
      to solve such conflicts. Research is scarce regarding positive conflict
      resolution strategies in a dating context. Considering research on various
      interpersonal relationships (e.g. friendships, dating, marriage), the present
      study examined how dimensions of empathy, verbal skills and impulsivity can
      contribute to the use of positive conflict resolution strategies in dating
      relationships. The sample is made up of 813 youth attending secondary schools or
      a regional college (71.7% female, mean age = 18.9, age range 14.2-24.9). They
      completed self-administered questionnaires investigating positive conflict
      resolution strategies, as well as dimensions of empathy (i.e., fantasy,
      perspective-taking, empathic concern, and personal distress), verbal skills
      (similarities and figurative language) and impulsivity (positive urgency,
      negative urgency, lack of premeditation, lack of perseverance, and sensation
      seeking). The results reveal sex differences and developmental improvements on
      several factors. The findings showed that specific dimensions of empathy and
      verbal skills foster the use of positive conflict resolution strategies whereas
      specific dimensions of impulsivity and one dimension of empathy hamper it. Both
      sexes shared a common correlate: the propensity toward perspective-taking
      fostered the use of positive conflict resolution strategies. In addition to
      highlighting correlates of positive conflict resolution strategies in dating
      relationships, this study can contribute to programs dedicated to the promotion
      of healthy dating relationships among adolescents and emerging adults.

PMID- 30238347
TI  - 1H, 15N and 13C resonance assignments of the C-terminal domain of the P protein
      of the Nishigahara strain of rabies virus.
AB  - The C-terminal domain of the P protein of rabies virus is a multifunctional
      domain that interacts with both viral and host cell proteins. Here we report the
      1H, 13C and 15N chemical shift assignments of this domain from P protein of the
      Nishigahara strain of rabies virus, a pathogenic laboratory strain well
      established for studies of virulence functions of rabies virus proteins,
      including P protein. The data and secondary structure analysis are in good
      agreement with the reported predominantly helical structure of the same domain
      from the CVS strain of rabies solved by crystallography. These assignments will
      enable future solution studies of the interactions of the P protein with viral
      and host proteins, and the effects of post-translational modifications.

PMID- 30238348
TI  - [Indications for transplantation and bridging procedures for primary
      hepatobiliary malignancies].
AB  - Primary hepatobiliary malignancies are hepatocellular carcinoma,
      cholangiocarcinoma and the rare hepatocellular cholangiocarcinoma (mixed tumor).
      The indications for liver transplantation and the oncological prognosis differ
      considerably between these tumor entities. Treatment and decision making for
      these tumors are often complicated by an underlying chronic liver disease. The
      aim of this review is to delineate the indications for transplantation and
      bridging therapies for each cancer entity as well as to highlight some aspects
      pertinent to transplantation, such as the principles of organ allocation.

PMID- 30238349
TI  - The prediction of the tumor size of a vestibular schwannoma by clinical
      performance and vestibular function tests.
AB  - PURPOSE: To investigate the relationship between vestibular schwannoma (VS) size
      and the dysfunction and compensation of the vestibular system. METHODS: One
      hundred fifty-two patients with unilateral VS were investigated using multiple
      auditory-vestibular function tests such as audiometry, sensory organization test
      (SOT), caloric test, cervical vestibular-evoked myogenic potential (cVEMP) test,
      and ocular VEMP (oVEMP) test. RESULTS: In this study, 89% of patients with
      unilateral VS had mild to severe hearing loss on the involved side. All patients
      showed higher threshold values or no response in the cVEMP and oVEMP tests, which
      both exhibited a lower response rate on the affected side than on the unaffected
      side. Patients with a tumor size >= 30 mm had significantly lower equilibrium
      scores for condition 5 and condition 6 of the SOT, which were associated with
      vestibular dysfunction, higher rates of canal paresis in the caloric test, and
      lower response rates in the cVEMP and oVEMP tests on the affected sides, compared
      with the results of patients with a tumor size <= 14 mm and patients with a tumor
      size of 15-29 mm. CONCLUSIONS: A diameter > 30 mm may be the critical threshold
      at which vestibular function is affected and vestibular compensation is
      interfered with by a VS tumor. Functional performance of the vestibular system
      can help clinicians predict the size of a tumor and provide a basis for the
      development of treatment protocols.

PMID- 30238351
TI  - [Medical examination: Preparation for ENT specialisation : Part 38].

PMID- 30238350
TI  - KX2-361: a novel orally bioavailable small molecule dual Src/tubulin inhibitor
      that provides long term survival in a murine model of glioblastoma.
AB  - PURPOSE: A major challenge to developing new therapies for patients with
      malignant brain tumors is that relatively few small molecule anticancer drugs
      penetrate the blood-brain barrier (BBB) well enough to provide therapeutically
      effective concentrations in brain tissue before drug exposure in non-CNS tissues
      results in unacceptable toxicity. METHODS: KX2-361, a member of a novel family of
      compounds with Src-kinase and tubulin polymerization inhibitory activity,
      demonstrates good oral bioavailability and readily crosses the BBB in mice. The
      objective of this study was to investigate the activity of KX2-361 against human
      and murine glioma cells and assess its therapeutic effect in a syngeneic
      orthotopic model of glioblastoma. RESULTS: In addition to reducing the level of
      Src autophosphorylation in the GL261 murine glioblastoma cell line, KX2-361 binds
      directly to tubulin and disrupts microtubule architecture in glioma cells
      maintained in culture. CONCLUSIONS: The drug is active in vivo against orthotopic
      GL261 gliomas in syngeneic C57BL/6 mice. Long term survival is not observed in
      mice lacking an adaptive immune system, indicating that KX2-361 works in concert
      with the host immune system to control tumor growth and promote long-term
      survival in the GL261 glioma model.

PMID- 30238352
TI  - Possible associations between palliative care conferences and positive outcomes
      when performing palliative care for patients with end-stage heart failure: a
      nationwide cross-sectional questionnaire survey.
AB  - Palliative care for end-stage heart failure should be provided by a
      multidisciplinary team. However, the influence of each occupational category on
      patients receiving palliative care for end-stage heart failure remains unclear.
      Thus, this study investigated the relationships between palliative care
      conferences and positive outcomes of palliative care for end-stage heart failure
      patients. We sent questionnaires to all cardiology training hospitals authorized
      by the Japanese Circulation Society (n = 1004); of these, responses from the
      directors at 554 institutions were analyzed. We divided the responding
      institutions into two groups according to their implementation of palliative care
      conferences for patients with end-stage heart failure. The institutions that had
      held such conferences (n = 223) had a larger number of hospital beds, beds in the
      cardiovascular department, and patients admitted to the cardiovascular
      department, compared with institutions that had not held these conferences (n =
      321). The usage rates of opioids, non-steroidal anti-inflammatory drugs, and
      sedatives were significantly higher in institutions that held these conferences.
      Multivariate analysis revealed that nutritionists and medical social workers had
      greater involvement in the improvement of mental symptoms and ensuring that
      patients could stay where they wished, respectively. The presence of palliative
      care physicians, physical therapists, or pharmacists was associated with multiple
      positive outcomes. This study indicated that there are possible associations
      between palliative care conferences and positive outcomes when performing
      palliative care for patients with end-stage heart failure.

PMID- 30238353
TI  - Pre-ablation levels of brain natriuretic peptide are independently associated
      with the recurrence of atrial fibrillation after radiofrequency catheter ablation
      in patients with nonvalvular atrial fibrillation.
AB  - Association between pre-ablation levels of biomarkers of cardiac and endothelial
      dysfunctions, CHADS2, CHA2DS2-VASc, and APPLE scores and the recurrence of atrial
      fibrillation (AF) after radiofrequency catheter ablation has not been fully
      studied. A total of 254 patients with nonvalvular AF were prospectively followed
      for AF recurrence after a single ablation procedure. During a two-year follow-up
      period, AF recurred in 65 (25.6%) patients. Patients with AF recurrence had
      significantly greater baseline ln brain natriuretic peptide (BNP) than those
      without AF recurrence (P < 0.01), whereas there were no significant differences
      in the levels of biomarkers of endothelial dysfunction and points of scoring
      systems. In the Cox regression analyses, the baseline ln BNP was significantly
      independently associated with AF recurrence (adjusted HR =1.286, 95% CI =1.000
      1.655, P < 0.05). The baseline levels of ln BNP were significantly associated
      with rhythm at blood collection, age, sex, and left atrial diameter, and left
      ventricular ejection fraction (P < 0.05).The subgroup analysis showed a
      significant interaction on the risk of AF recurrence between ln BNP, sex
      difference, and rhythm at blood collection (P for interaction < 0.05). In
      conclusion, the results suggest that the pre-ablation levels of ln BNP are useful
      to evaluate the risk of AF recurrence after ablation therapy; however, there is a
      need to be careful while using BNP as a biomarker for the risk of AF recurrence
      by taking account of the effects of rhythm status at blood collection and sex
      difference.

PMID- 30238354
TI  - Ivabradine Aggravates the Proarrhythmic Risk in Experimental Models of Long QT
      Syndrome.
AB  - Ivabradine has recently been demonstrated to have antiarrhythmic properties in
      atrial fibrillation. The aim of the present study was to assess the
      electrophysiologic profile of ivabradine in an experimental whole-heart model of
      long-QT-syndrome. In 12 isolated rabbit hearts long-QT-2-syndrome (LQT2) was
      simulated by infusion of D,L-sotalol (100 uM). 12 rabbit hearts were treated with
      veratridine (0.5 uM) to mimic long-QT-3-syndrome (LQT3). Sotalol induced a
      significant prolongation of QT-interval (+ 40 ms, p < 0.01) and action potential
      duration (APD, + 20 ms, p < 0.01). Similar results were obtained in veratridine
      treated hearts (QT-interval: +52 ms, p < 0.01; APD: + 41 ms, p < 0.01). Of note,
      both sotalol (+ 26 ms, p < 0.01) and veratridine (+ 42 ms, p < 0.01)
      significantly increased spatial dispersion of repolarisation. Additional infusion
      of ivabradine (5 uM) did not change these parameters in sotalol-pretreated hearts
      but resulted in a further significant increase of QT-interval (+ 26 ms, p < 0.05)
      and APD (+ 49 ms, p < 0.05) in veratridine-treated hearts. Lowering of potassium
      concentration in bradycardic AV-blocked hearts resulted in the occurrence of
      early afterdepolarizations (EAD) or polymorphic ventricular tachycardias (VT)
      resembling torsade de pointes in 6 of 12 sotalol-treated hearts (56 episodes) and
      6 of 12 veratridine-treated hearts (73 episodes). Additional infusion of
      ivabradine increased occurrence of polymorphic VT. Ivabradine treatment resulted
      in occurrence of EAD and polymorphic VT in 9 of 12 sotalol-treated hearts (212
      episodes), and 8 of 12 veratridine-treated hearts (155 episodes). Treatment with
      ivabradine in experimental models of LQT2 and LQT3 increases proarrhythmia. A
      distinct interaction with potassium currents most likely represents a major
      underlying mechanism. These results imply that ivabradine should be employed with
      caution in the presence of QT-prolongation.

PMID- 30238355
TI  - Protective Effects of a Novel Agonist of Galanin Receptors Against Doxorubicin
      Induced Cardiotoxicity in Rats.
AB  - The clinical use of antineoplastic agent doxorubicin (DOX) is limited due to its
      cardiotoxic action. [betaAla14, His15]-galanine (2-15) (G) is a novel synthetic
      agonist of galanin receptors GalR1-3 having cardioprotective properties in animal
      models in vivo. The aim of the present study was to explore effects of G on DOX
      induced cardiotoxicity. Wistar rats were divided into four groups and treated
      with DOX (D group), DOX and G (D + G group), G (G group), and saline (control).
      Before treatment and at the end of the study, concentration of thiobarbituric
      acid reactive substances (TBARS) and activity of creatine kinase-MB (CK-MB) were
      determined in blood plasma, the animals were weighed, and cardiac function was
      evaluated by echocardiography. At the end of experiments, the hearts were used to
      determine energy metabolites and mitochondrial respiration in permeabilized
      fibers. After an 8-week study, D group exhibited a pronounced cardiac failure,
      the absence of weight gain, an increased plasma TBARS concentration, and CK-MB
      activity. These disorders were accompanied by a reduced myocardial content of
      high-energy phosphates and mitochondrial respiratory parameters. Co
      administration of G with DOX significantly decreased plasma TBARS level and
      prevented an increase in plasma CK-MB activity. In D + G group, myocardial
      contents of ATP, PCr, total adenine nucleotides, and total creatine as well as
      myocardial PCr/ATP ratio and the respiratory control index were higher than in D
      group at the end of the experiments. Peptide G significantly improved parameters
      of left ventricular (LV) function and caused weight gain in animals of D + G
      group. These results suggest that peptide G may be a potential pharmacological
      agent that attenuates the cardiotoxic effects of DOX.

PMID- 30238357
TI  - Clinical feasibility of early scanning after administration of 68Ga-DOTATOC.
AB  - OBJECTIVE: Positron emission tomography (PET)/computed tomography (CT) using 68Ga
      labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid-D-Phe1-Tyr3
      octreotide (DOTATOC) is usually performed about 1-h post-injection; however,
      because of rapid blood clearance, the waiting time for scanning could possibly be
      shortened without affecting diagnostic performance. The purpose of this study was
      to investigate the feasibility of early scanning at 30 min post-injection.
      METHODS: Thirty-eight patients who underwent DOTATOC-PET/CT were analyzed. After
      administration of 68Ga-DOTATOC, data acquisition was performed twice, at 30-min
      and 60-min post-injection. The number of known or suspected pathological lesions,
      and quantitative values of those lesions and physiological uptake were compared.
      SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion uptake (TLU) were
      calculated as quantitative values of the pathological lesions. RESULTS: A total
      of 125 known or suspected pathological lesions were found at both timepoints,
      with no differences between the two datasets. The SUVmax, SUVpeak, MTV, and TLU
      were highly reproducible, with Spearman's rho of 0.983, 0.986, 0.918, and 0.981,
      respectively. The average percent differences (%DIFFave) defined as the
      differences of the values divided by the value at 1-h post-injection were 11.1%
      for SUVmax, 8.5% for SUVpeak, 15.1% for MTV, and 20.6% for TLU. Physiological
      uptake in the two datasets was closely comparable in the pituitary gland
      (Spearman's rho = 0.954, %DIFFave = 11.0%), liver (0.989, 3.9%), spleen (0.970,
      6.3%), adrenal glands (0.879, 13.0%), and pancreatic uncus (0.946, 12.7%).
      CONCLUSION: The diagnostic performance of visual interpretation should be
      comparable between DOTATOC-PET/CT images obtained at 30-min and 60-min post
      injection. Some differences between quantitative values may exist; however, they
      appear to be minimal.

PMID- 30238356
TI  - The role of mechanical bowel preparation and oral antibiotics for left-sided
      laparoscopic and open elective restorative colorectal surgery with and without
      faecal diversion.
AB  - BACKGROUND: There is significant variation in the use of mechanical bowel
      preparation and oral antibiotics prior to left-sided elective colorectal surgery.
      There has been no consensus internationally. METHODS: This was a retrospective
      analysis of the 2015 American College of Surgeons National Surgical Quality
      Improvement Program database. Patients were divided into four groups: those who
      had mechanical bowel preparation with oral antibiotics, mechanical bowel
      preparation alone, oral antibiotics alone and no preparation. The main outcome
      measures included overall, superficial, deep and organ/space surgical site
      infections. Secondary outcomes included anastomotic leak, ileus and rate of
      Clostridium difficile. RESULTS: A total of 5729 patients were included for
      analysis. The overall surgical site infection rate (any superficial, deep or
      organ/space infection) was significantly lower in the mechanical bowel
      preparation and oral antibiotics approach when compared to no preparation (OR =
      0.46, 95% CI 0.36-0.59, P < 0.0001). On multivariable logistic regression
      analysis, mechanical bowel preparation with oral antibiotics maintained a lower
      risk of overall surgical site infections. MBP and OAB also had a protective
      effect on anastomotic leak in both the laparoscopic and open cohorts
      (laparoscopic multivariable adjusted OR = 0.42 (0.19-0.94), P = 0.035; open
      multivariable adjusted OR = 0.3 (0.12-0.77), P = 0.012). Mechanical bowel
      preparation alone and oral antibiotics alone was not associated with a
      significant decrease in surgical site infections. There was no increase in C.
      difficile occurrences with the use of oral antibiotics. CONCLUSION: Mechanical
      bowel preparation with oral antibiotics significantly minimised surgical site
      infections and anastomotic leak following both laparoscopic and open left-sided
      restorative colorectal surgery. Mechanical bowel preparation alone did not reduce
      surgical site infections. There was a trend to reduction in surgical site
      infections with oral antibiotics alone.

PMID- 30238359
TI  - Pathological findings of late total occlusion after Zilver PTX stent implantation
      in restenosis lesion of bare-metal nitinol stent for superficial femoral artery.

PMID- 30238358
TI  - What influences a pet dog's first impression of a stranger?
AB  - Dogs live in the dynamic human social networks full of strangers, yet they form
      strong and selective bonds with familiar caretakers. Little is known about how a
      bond is initially formed between a dog and a complete stranger. The first
      impression hypothesis suggests that interacting with strangers can present an
      opportunity to form a mutualistic partnership. It predicts that dogs should
      respond positively toward a complete stranger to facilitate bonding (Prediction
      1) and adjust their preferences in response to the perceived risk and benefit of
      interacting with strangers (Prediction 2). We examine the social preferences of
      pet dogs toward a complete stranger whom they have never met before and several
      other potential partners - the owner with whom subjects have had a positive, long
      term bond (Experiment 1), and an exposed stranger with whom they have had a
      positive short-term interaction (Experiment 2) or a negative one (Experiment 3).
      In support of Prediction 1, subjects were exceptionally trusting across contexts.
      Mixed results were found with regard to Prediction 2. Subjects preferred their
      owner over a stranger when following social cues and (to a lesser degree) when
      approaching and feeding in close proximity. However, relative to a complete
      stranger, subjects did not consistently prefer the positively exposed stranger or
      avoid the negatively exposed one. The lack of clear selectivity might be due to
      pet dogs' high baseline level of trust of complete strangers or reflect the
      strength of their existing bonds that negated the need for another positive bond
      with a new human partner.

PMID- 30238360
TI  - Limitations of Water Resources Infrastructure for Reducing Community
      Vulnerabilities to Extremes and Uncertainty of Flood and Drought.
AB  - Debate and deliberation surrounding climate change has shifted from mitigation
      toward adaptation, with much of the adaptation focus centered on adaptive
      practices, and infrastructure development. However, there is little research
      assessing expected impacts, potential benefits, and design challenges that exist
      for reducing vulnerability to expected climate impacts. The uncertainty of design
      requirements and associated government policies, and social structures that
      reflect observed and projected changes in the intensity, duration, and frequency
      of water-related climate events leaves communities vulnerable to the negative
      impacts of potential flood and drought. The results of international research
      into how agricultural infrastructure features in current and planned adaptive
      capacity of rural communities in Argentina, Canada, and Colombia indicate that
      extreme hydroclimatic events, as well as climate variability and unpredictability
      are important for understanding and responding to community vulnerability. The
      research outcomes clearly identify the need to deliberately plan, coordinate, and
      implement infrastructures that support community resiliency.

PMID- 30238361
TI  - Simulation and experimental validation of a gradient feeding system for fast
      assessment of the kinetic behavior of a microbial consortium in a tubular biofilm
      reactor.
AB  - This study deals with the mathematical simulation and experimental validation of
      a gradient system for the gradual change of the imidacloprid loading rate to a
      tubular biofilm reactor (TBR). The strategy was used for fast studies of the
      kinetic and stoichiometric impact caused by the increase in the pesticide loading
      rate in a TBR, running in plug flow regime. Seemingly, this strategy has never
      been used for biokinetic and stoichiometric studies in biofilm reactors. For this
      purpose, a mathematical model describing the substrate transient behavior Sg(t)
      in a concentration gradient generator system using variable volume tanks is
      proposed. A second model, representing the temporary variation in the loading
      rate of imidacloprid to an aerated equalizer tank preceding the packed zone of
      the TBR, is also presented. Both models were experimentally confirmed. After the
      treatment of the experimental data, the kinetic and stoichiometric changes
      occurring in the TBR, caused by the gradual increase in the imidacloprid loading
      rate, were readily evaluated. Although the structure of the microbial community,
      at the phylum level, showed similar behavior along the tubular reactor, the
      stress produced by the gradual increase in imidacloprid concentration had
      functional consequences on the mixed microbial populations which were reflected
      on the stoichiometric and kinetic parameters. After increasing more than five
      times the imidacloprid loading rate to the TBR, the imidacloprid removal
      efficiency decayed about 40%, and the microbial-specific removal rate of the
      insecticide showed a decrease of about 30%.

PMID- 30238362
TI  - Recent progress of algae and blue-green algae-assisted synthesis of gold
      nanoparticles for various applications.
AB  - The hazardous effects of current nanoparticle synthesis methods have steered
      researchers to focus on the development of newer environmentally friendly and
      green methods for synthesizing nanoparticles using nontoxic chemicals. The
      development of environmentally friendly methods of nanoparticle synthesis with
      different sizes and shapes is one of the pressing challenges for the current
      nanotechnology. Several novel green approaches for the synthesis of AuNPs have
      been explored using different natural sources, such as plants, algae, bacteria,
      and fungi. Among organisms, algae and blue-green algae are of particular interest
      for nanoparticle synthesis. Gold nanoparticles (AuNPs) have a range of
      applications in medicine, diagnostics, catalysis, and sensors because of their
      significant key roles in important fields. AuNPs have attracted a significant
      interest for use in a variety of applications. The widespread use of AuNPs can be
      accredited to a combination of optical, physical, and chemical properties as well
      as the miscellany of size, shape, and surface composition that has been adopted
      through green synthesis methods.

PMID- 30238363
TI  - Biomechanical Properties and Mechanobiology of Cardiac ECM.
AB  - The heart is comprised of cardiac cells and extracellular matrix (ECM) which
      function together to pump blood throughout the body, provide organs with
      nutrients and oxygen, and remove metabolic wastes. Cardiac ECM provides a
      scaffold to cardiac cells and contributes to the mechanical properties and
      function of the cardiac tissue. Recently, more evidence suggests that cardiac ECM
      plays an active role in cardiac remodeling in response to mechanical loads. To
      that end, we provide an overview of the structure and function of the heart and
      the currently available in vivo and ex vivo mechanical measurements of cardiac
      tissues. We also review the biomechanical properties of cardiac tissues including
      the myocardium and heart valves, with a discussion on the differences between the
      right ventricle and left ventricle. Lastly, we go into the mechanical factors
      involved in cardiac remodeling and review the mechanobiology of cardiac tissues,
      i.e., the biomechanical responses at the cellular and tissue level, with an
      emphasis on the impact on the cardiac ECM. The regulation of cardiac ECM on cell
      function, which is a new and open area of research, is also briefly discussed.
      Future investigation into the ECM deposition and the interaction of cardiac cells
      and ECM components for mechanotransduction can assist to understand cardiac
      remodeling and inspire new therapies for cardiac diseases.

PMID- 30238364
TI  - Imaging the Cardiac Extracellular Matrix.
AB  - Cardiovascular disease is the global leading cause of death. One route to address
      this problem is using biomedical imaging to measure the molecules and structures
      that surround cardiac cells. This cellular microenvironment, known as the cardiac
      extracellular matrix, changes in composition and organization during most cardiac
      diseases and in response to many cardiac treatments. Measuring these changes with
      biomedical imaging can aid in understanding, diagnosing, and treating heart
      disease. This chapter supports those efforts by reviewing representative methods
      for imaging the cardiac extracellular matrix. It first describes the major
      biological targets of ECM imaging, including the primary imaging target of
      fibrillar collagen. Then it discusses the imaging methods, describing their
      current capabilities and limitations. It categorizes the imaging methods into two
      main categories: organ-scale noninvasive methods and cellular-scale invasive
      methods. Noninvasive methods can be used on patients, but only a few are
      clinically available, and others require further development to be used in the
      clinic. Invasive methods are the most established and can measure a variety of
      properties, but they cannot be used on live patients. Finally, the chapter
      concludes with a perspective on future directions and applications of biomedical
      imaging technologies.

PMID- 30238365
TI  - Animal Models and Cardiac Extracellular Matrix Research.
AB  - Cardiovascular disease has been the leading cause of death worldwide for the last
      15 years, accounting for 15 million deaths per year. While interventions are
      saving more lives, more than 20% of survivors will end up in heart failure. Cell
      based and other types of therapy for advanced heart and vascular disease may
      offer new hope for those afflicted. Although a variety of cell types are under
      investigation, common issues include cell survival, retention, engraftment, and
      proliferation. Cardiac extracellular matrix (C-ECM) has compelling features that
      offer advantages to not only aid cell survival, retention, engraftment, and
      proliferation but likely has independent therapeutic (paracrine) and mechanical
      effects. Animal studies and clinical trials are underway to characterize the role
      of C-ECM and demonstrate efficacy for acute and chronic heart disease. This
      chapter reviews animal models used to enhance our knowledge of C-ECMs in heart
      disease and its use in the treatment of heart disease.

PMID- 30238366
TI  - Applications of Cardiac Extracellular Matrix in Tissue Engineering and
      Regenerative Medicine.
AB  - The role of the cardiac extracellular matrix (cECM) in providing biophysical and
      biochemical cues to the cells housed within during disease and development has
      become increasingly apparent. These signals have been shown to influence many
      fundamental cardiac cell behaviors including contractility, proliferation,
      migration, and differentiation. Consequently, alterations to cell phenotype
      result in directed remodeling of the cECM. This bidirectional communication means
      that the cECM can be envisioned as a medium for information storage. As a result,
      the reprogramming of the cECM is increasingly being employed in tissue
      engineering and regenerative medicine as a method with which to treat disease. In
      this chapter, an overview of the composition and structure of the cECM as well as
      its role in cardiac development and disease will be provided. Additionally,
      therapeutic modulation of cECM for cardiac regeneration as well as bottom-up and
      top-down approaches to ECM-based cardiac tissue engineering is discussed.
      Finally, lingering questions regarding the role of cECM in tissue engineering and
      regenerative medicine are offered as a catalyst for future research.

PMID- 30238367
TI  - Whole Cardiac Tissue Bioscaffolds.
AB  - Bioscaffolds serve as structures for cells in building complex tissues and full
      organs including heart. Decellularizing cardiac tissue results in cell-free
      extracellular matrix (ECM) that can be used as a cardiac tissue bioscaffold. The
      field of whole-heart tissue engineering has been revolutionized since the 2008
      publication of the first perfusion-decellularized whole heart, and since then,
      studies have shown how decellularized cardiac tissue retains its native
      architecture and biochemistry following recellularization. Chemical, enzymatic,
      and physical decellularization methods preserve the ECM to varying degrees with
      the widely accepted standard of less than 50 ng/mg of double-stranded DNA present
      in decellularized ECM. Following decellularization, replacement of cells occurs
      via recellularization: seeding cells into the decellularized ECM structure either
      via perfusion of cells into the vascular conduits, injection into parenchyma, or
      a combination of perfusion and injection. Endothelial cells are often perfused
      through existing vessel conduits to provide an endothelial lining of the
      vasculature, with cardiomyocytes and other parenchymal cells injected into the
      myocardium of decellularized ECM bioscaffolds. Uniform cell density and cell
      retention throughout the bioscaffold still needs to be addressed in larger animal
      models of the whole heart. Generating the necessary cell numbers and types
      remains a challenge. Still, recellularized cardiac tissue bioscaffolds offer
      therapeutic solutions to heart failure, heart valve replacement, and acute
      myocardial infarction. New technologies allow for decellularized ECM to be
      bioprinted into cardiac bioscaffolds or formed into a cardiac hydrogel patch.
      This chapter reviews the advances made in decellularization and recellularization
      of cardiac ECM bioscaffolds with a discussion of the potential clinical
      applications of ECM bioscaffolds.

PMID- 30238368
TI  - Natural Sources of Extracellular Matrix for Cardiac Repair.
AB  - Tissue engineering and regenerative medicine have adopted the use of
      extracellular matrix (ECM) as a cell delivery device and bioactive regenerative
      agent. To this end, many ECMs have been investigated for cardiac tissue
      engineering and regenerative medicine applications with variable success. Many
      sources of natural ECMs have been tested for cardiac applications. Typically,
      natural ECMs have been made from decellularized organs or tissues and processed
      into either sheets or injectable hydrogels. This chapter will review natural
      sources of ECM materials that have been tested as therapeutic agents in models of
      heart failure.

PMID- 30238369
TI  - Cardiac Extracellular Matrix Modification as a Therapeutic Approach.
AB  - The cardiac extracellular matrix (cECM) is comprised of proteins and
      polysaccharides secreted by cardiac cell types, which provide structural and
      biochemical support to cardiovascular tissue. The roles of cECM proteins and the
      associated family of cell surface receptor, integrins, have been explored in vivo
      via the generation of knockout experimental animal models. However, the
      complexity of tissues makes it difficult to isolate the effects of individual
      cECM proteins on a particular cell process or disease state. The desire to
      further dissect the role of cECM has led to the development of a variety of in
      vitro model systems, which are now being used not only for basic studies but also
      for testing drug efficacy and toxicity and for generating therapeutic scaffolds.
      These systems began with 2D coatings of cECM derived from tissue and have
      developed to include recombinant ECM proteins, ECM fragments, and ECM mimics.
      Most recently 3D model systems have emerged, made possible by several developing
      technologies including, and most notably, 3D bioprinting. This chapter will
      attempt to track the evolution of our understanding of the relationship between
      cECM and cell behavior from in vivo model to in vitro control systems. We end the
      chapter with a summary of how basic studies such as these have informed the use
      of cECM as a direct therapy.

PMID- 30238370
TI  - Extracellular Matrix for Myocardial Repair.
AB  - Multiple strategies have been investigated to restore functional myocardium
      following injury or disease including the local administration of cytokines or
      chemokines, stem/progenitor cell therapy, mechanical circulatory support,
      pharmacologic use, and the use of inductive biomaterials. The use of xenogeneic
      biologic scaffolds composed of extracellular matrix (ECM) has been shown to
      facilitate functional restoration of several tissues and organs including the
      esophagus, skeletal muscle, skin, and myocardium, among others. The present
      chapter describes the current understanding of specific components of biologic
      scaffolds composed of ECM, the mechanisms by which ECM bioscaffolds promote
      constructive cardiac remodeling after injury, determinants of remodeling outcome,
      and the versatility of ECM as a potential cardiac therapeutic.

PMID- 30238371
TI  - Role of Extracellular Matrix in Cardiac Cellular Therapies.
AB  - The extracellular matrix (ECM) is an essential regulator of homeostasis at the
      cellular, tissue, and organ level. It is now very well known that ECM dynamic
      remodeling is indispensable not only for normal growth and development but also
      recovery from tissue injuries. Indeed, abnormal remodeling of the ECM plays a
      major role in many pathophysiological processes and contributes to many different
      pathologies including cardiovascular disorders. Recently, cellular therapies have
      emerged as a potential therapeutic strategy for restoration of lost
      cardiomyocytes or their rejuvenation after cardiac damage and injuries.
      Harnessing the biological properties of ECM could be a viable strategy to enhance
      the therapeutic effects of cellular therapies by improving the engraftment,
      integration, survival, and functional adaptation of newly transplanted cells in
      many different platforms. Conversely, transplanted cells could restore the
      functionality and original composition of damaged ECM by secreting and depositing
      new ECM or stimulating normal ECM production by cardiac tissue native cells.
      Although the ultimate role of cell therapy in treatment of cardiac disorders is
      still a matter of great debate, the potential utility of ECM in improving the
      therapeutic effect of transplanted cells and vice versa the potential role of
      cell therapy as a means to restore the structure and functionality of damaged ECM
      should be carefully considered in implementation of future clinical
      cardiovascular cell therapy trials.

PMID- 30238372
TI  - Regulation of Regenerative Medicine Products.
AB  - Cellular therapies have moved to the forefront based upon promising results from
      clinical trials using both chimeric antigen receptor T lymphocytes to treat
      leukemia and other cell types to restore structure and function to tissues that
      have been damaged by disease or physical injury. The pace at which these
      treatments have evolved has posed a regulatory challenge to agencies, such as the
      Food and Drug Administration (FDA). This chapter describes how a specific
      regulatory strategy was developed and how it has evolved in response to the
      demand for these new therapies.

PMID- 30238373
TI  - Clinical Trial Design for Investigational Cardio-Regenerative Therapy.
AB  - Human trials of cardio-regenerative biologic therapies are being performed
      worldwide to address a growing, unmet need for durable treatments of
      cardiovascular disease. A well-constructed clinical trial design for these novel
      therapies requires careful attention to defining a clear hypothesis, a patient
      population, and anticipated outcomes. The scope of screening, method of
      randomization, blinding approach, data monitoring, and statistical analysis plan
      are the foundational elements that must be addressed in any clinical trial.
      Although the experience of human trials involving extracellular matrix constructs
      for cardiovascular disease treatment is limited, numerous lessons have been
      learned in the field of cell therapy that are translatable across all biologic
      treatment options. Future progress in this field may include testing combinations
      of cells, gene-transfer agents, and matrix and identifying treatment responders
      versus nonresponders.

PMID- 30238374
TI  - Regenerative Medicine Venturing at the University-Industry Boundary: Implications
      for Institutions, Entrepreneurs, and Industry.
AB  - Regenerative medicine research at university laboratories has outpaced commercial
      activity. Legal, regulatory, funding, technological, and operational uncertainty
      have slowed market entry of regenerative medicine treatments. As a result,
      commercial development has often been led by entrepreneurial ventures rather than
      large biopharma firms. Translating regenerative medicine across the university
      industry boundary links academic scientists, technology transfer organizations,
      funders, and entrepreneurs. Conflicting motivations among the participants may
      significantly hinder these efforts. Unproven downstream business models for
      regenerative medicine delivery further complicate the entrepreneurial process.
      This chapter explores the challenges associated with entrepreneurial activity
      commercializing regenerative medicine science developed at research institutions.

PMID- 30238376
TI  - Near Infrared Spectroscopic Evaluation of Ligament and Tendon Biomechanical
      Properties.
AB  - Knee ligaments and tendons are collagen-rich viscoelastic connective tissues that
      provide vital mechanical stabilization and support to the knee joint.
      Deterioration of ligaments has an adverse effect on the health of the knee and
      can eventually lead to ligament rupture and osteoarthritis. In this study, the
      feasibility of near infrared spectroscopy (NIRS) was, for the first time, tested
      for evaluation of ligament and tendon mechanical properties by performing
      measurements on bovine stifle joint ligament (N = 40) and patellar tendon (N =
      10) samples. The mechanical properties of the samples were determined using a
      uniaxial tensile testing protocol. Partial least squares regression models were
      then developed to determine if morphological, viscoelastic, and quasi-static
      properties of the samples could be predicted from the NIR spectra. Best
      performance of NIRS in predicting mechanical properties was observed for
      toughness at yield point (median [Formula: see text], median normalized [Formula:
      see text]), toughness at failure point (median [Formula: see text], median
      normalized [Formula: see text]), and the ultimate strength of the ligament/tendon
      (median [Formula: see text], median normalized [Formula: see text]). Thus, we
      show that NIRS is capable of estimating ligament and tendon biomechanical
      properties, especially in parameters related to tissue failure. We believe this
      method could substantially enhance the currently limited arthroscopic evaluation
      of ligaments and tendons.

PMID- 30238375
TI  - Antimicrobial Therapy in Community-Acquired Pneumonia in Children.
AB  - PURPOSE OF REVIEW: Empirical antibiotic therapy remains the cornerstone of
      treatment in community-acquired pneumonia (CAP). However, the best option for
      empirical antibiotics for treatment on an ambulatory basis, as well as in those
      requiring hospitalization, is still unclear. This review tries to answer the
      question regarding the most appropriate antibiotics in different settings in
      children with CAP as well as duration of therapy. RECENT FINDINGS: Recent studies
      have provided insights regarding use of oral antibiotics in children with mild to
      moderate CAP, and severe CAP with lower chest retractions but no hypoxia. In view
      of rapidly emerging resistance among various causative pathogens, several new
      drugs have been currently approved, or are under trial for CAP in children.
      Current knowledge suggests that the choice of antibiotics for ambulatory
      treatment of CAP is oral amoxicillin with a duration of 3-5 days. Children with
      CAP with lower chest retractions but no hypoxia can be treated with oral
      amoxicillin. Severe pneumonia can be treated with intravenous antibiotics
      consisting of penicillin/ampicillin with or without an aminoglycoside. Several
      new drugs have been developed and approved for use in CAP caused by multidrug
      resistant organisms, but these should be used judiciously to avoid emergence of
      further resistance. Future research is needed regarding the safety and efficacy
      of newer drugs in children.

PMID- 30238377
TI  - The Romanian experience and perspective on the commercial cultivation of
      genetically modified crops in Europe.
AB  - Romania was the third country in Europe and the tenth in the world, to
      commercially adopt genetically modified crops in 1999, only 3 years after they
      were first marketed globally. Half a million hectares of transgenic herbicide
      resistant soybean and insect resistant maize were grown in Romania during an
      uninterrupted 17-year period. After several years of continued declining area,
      the commercial cultivation of transgenic plants recently ended. The commercial
      cultivation of transgenic crops in Romania remains legally and technically
      possible, according to the EU and national regulations. However, the declining
      area cultivated with these crops in Romania seems to be the result of farmers'
      conscious decision, while waiting for more profitable genetically modified crops
      to become available that better fit their needs. This expectation would be a
      logical result of the EU GMO opt-out Directive 2015/412 and the advent of the new
      plant breeding techniques. The GMO opt-out mechanism is still expected to unblock
      the EU authorization process after the large majority of the EU member states
      have already prohibited the cultivation of genetically modified organisms in
      their territory. As the new plant breeding techniques offer significant technical
      and economic advantages, they could be rapidly adopted by commercial breeders and
      farmers outside Europe. The Court of Justice of the European Union ruled that
      plants obtained with the new gene editing techniques must go through the same
      authorization procedure as transgenic plants. This decision is expected to delay
      the approval and availability of these new plant varieties on the EU market and
      their commercial cultivation.

PMID- 30238378
TI  - Clinical description of patients with cytoplasmic discrete dots pattern
      (lysosome) on indirect immunofluorescence on HEp-2 cells.
AB  - The cytoplasmic discrete dot (CDD) pattern is an unusual finding in indirect
      immunofluorescence, and its clinical value is unknown. To describe the clinical
      characteristics of patients with CDD pattern on indirect immunofluorescence (IIF)
      from our laboratory database and to evaluate possible associations with other
      autoantibodies and autoimmune diseases. This is a retrospective descriptive
      study. We included all patients with CDD pattern on IIF in HEp-2 cells with a
      titer equal or greater than 1/80, using a database of all IIF performed in a
      reference immunology and rheumatology laboratory between 2007 and 2015. Data on
      demographics, past medical history, and relevant laboratory findings were
      recorded and analyzed. We performed 13.056 IIF on HEp-2 cells tests between
      January 1, 2007 and December 31, 2015, with 6075 positive results. Among them,
      5447 had nuclear pattern, 55 had both nuclear and cytoplasmic pattern, and 573
      had cytoplasmic pattern. Only 21 showed a CDD pattern. Four patients were
      excluded since they did not have medical records at the institution. The
      prevalence of the CDD pattern in our laboratory was 0.35%. The median age was of
      62.3 years (SD 9.16) and 100% were female. Fifty-three percent (9/17) had an
      autoimmune disease, Hashimoto's thyroiditis (4/9) being the most frequent one. In
      conclusion, cytoplasmic discrete dot pattern is an uncommon finding and its
      clinical value is uncertain. However, in our study, 53% of the patients had an
      autoimmune disease.

PMID- 30238379
TI  - Impact of biologics on disease course in systemic onset juvenile idiopathic
      arthritis.
AB  - To analyze our cohort of patients with systemic onset juvenile idiopathic
      arthritis (SoJIA) and investigate the impact of biologic disease-modifying
      antirheumatic drugs (BDMARDs) on disease course. Children who were diagnosed with
      SoJIA according to International League of Associations for Rheumatology (ILAR)
      criteria in Boston Children's Hospital between January 1996 and December 2015
      were included. Data were collected from patients' charts retrospectively.
      Demographic features, disease course, and medication usage were identified. There
      were 76 patients who met ILAR criteria. Most common presenting features were
      fever (100%), arthralgia (92%), rash (87%), and arthritis (83%). Median follow-up
      was 69 months. At last visit, 18% still had active disease. Disease course was
      monophasic in 18 patients (24%), persistent in 24 patients (32%), and polycyclic
      in 34 patients (45%). Thirty-three percent (n, 6) of children with monophasic
      disease was diagnosed before 2004 and 67% (n, 12) was diagnosed after 2004 (p =
      0.08). Sixty-six percent was treated with a BDMARD. Anakinra (37%) was the most
      common prescribed BDMARD. Monophasic disease was less common in patients treated
      with a BDMARD (n, 6, 12%) compared to children not treated with a BDMARD (n, 12,
      46%) (p = 0.01). BDMARDs are started earlier (rs, - 0.67; p < 0.001) and
      diagnosis of SoJIA is made sooner after symptom onset in recent years (rs, -
      0.37; p = 0.001). Most patients in our cohort were able to achieve remission.
      Proportion of monophasic disease tends to increase after 2004 although not
      statistically significant. In recent years, physicians tend to diagnose SoJIA
      earlier and treat more aggressively early in the course of the disease with
      BMARDs. Future prospective research in larger cohorts investigating the effects
      of BDMARDs on disease course and predictive factors for outcome is needed.

PMID- 30238380
TI  - Management of anti-HBc-positive patients with rheumatic diseases treated with
      disease-modifying antirheumatic drugs-a single-center analysis of 2054 patients.
AB  - Hepatitis B virus (HBV) reactivation is a common complication of
      immunosuppressive treatment in high prevalence countries. Biological disease
      modifying antirheumatic drugs (bDMARDs) cause this adverse event more often than
      conventional immunosuppressants. The incidence of HBV reactivation during
      treatment for rheumatic diseases in Germany is unclear. Furthermore, it remains
      open how to treat and monitor patients at risk during immunosuppressive therapy
      with bDMARDs. We examined 2054 patients from a German tertiary rheumatology
      center in order to analyze the prevalence of HBc-antibody-positivity and the
      incidence of HBV reactivation in German rheumatology patients treated with
      immunosuppressants. Of 1317 patients treated with bDMARDs and 737 conventional
      synthetic DMARD (csDMARDs) patients between 2008 and 2017, 86 had a history of
      HBV infection (anti-HBc positive). Only two patients were suffering from chronic
      infection (HBsAg positive). Three patients were treated pre-emptively with
      entecavir, and eight patients after HBV DNA reappearance. No liver failure
      occurred due to HBV reactivation. Compared to anti-HBc-positive patients without
      reactivation, the reactivation group included more patients exposed to three or
      more classes of bDMARDs (p = 0.017). The median HBs antibody titer was
      significantly lower in the reactivation group (15.0 IU/l vs. 293.5 IU/l; p =
      0.001). This study shows that bDMARDs and csDMARDs can safely be administered to
      patients with a history of HBV, provided they are closely monitored. Low titers
      of anti-HBs antibodies and a history of >= 3 classes of immunosuppressants
      increase the risk of HBV reactivation. These data highlight major differences to
      high prevalence regions.

PMID- 30238381
TI  - Dysregulation of the Wnt signaling pathway in South African patients with diffuse
      systemic sclerosis.
AB  - The objective was to explore changes in gene expression in Wnt pathway genes in
      skin samples of black South Africans with diffuse cutaneous systemic sclerosis
      (dcSSc). Affected (forearm) and unaffected (upper back) skin samples of eight
      Black South Africans with active early dcSSc were compared to skin samples from
      seven ethnically matched control subjects. The Wnt Pathway Plus RT2 Profiler qPCR
      Array was used to determine gene expression and analyzed for differential
      expression between cases and controls. Selective validation was done using single
      gene TaqMan assays. Several genes were similarly upregulated in both affected and
      unaffected skin of the dcSSc patients compared to controls. These included the
      Wnt ligands WNT7A and WNT10A, the frizzled receptors FZD8 and FZD9, intracellular
      signaling proteins AXIN1 and AXIN2, and the pathway target genes FGF4 and MMP7.
      Principal component analysis revealed patients clustering into two groups, which
      co-segregated with clinical features of interstitial lung disease and/or
      inflammatory myopathy, or the absence of an inflammation phenotype. These two
      groups showed paradoxical gene expression of the genes TCF7, SOX17, and FRZB in
      affected and unaffected skin. This study provides further evidence of
      dysregulation of gene expression at various levels of the Wnt signaling pathway
      in dcSSc. Moreover, principal component analysis showed two distinct patient
      clusters of gene expression, which co-segregated with the presence or absence of
      clinical inflammatory features, and may reflect different pathological pathways
      in dcSSc.

PMID- 30238383
TI  - Tubular dysfunction in extremely low birth weight survivors.
AB  - BACKGROUND: Extremely low birth weight (ELBW) survivors may develop
      glomerulosclerosis due to low nephron number, whereas their tubular function
      remains unknown except for hypercalciuria and phosphaturia. METHODS: Fifty-three
      subjects (30 boys and 23 girls, aged 7 months-19 years, median 36 months) were
      studied retrospectively. The median gestational age and birth weight were 26
      weeks (range 22-32) and 745 g (range 316-999), respectively. Urine calcium-to
      creatinine ratio (Ca/Cr), N-acetyl-beta-D-glucosaminidase-to-creatinine ratio
      (NAG/Cr), beta2 microglobulin-to-creatinine ratio (beta2m/Cr), uric acid-to
      creatinine ratio (UA/Cr), glucose-to-creatinine ratio (glu/Cr), and microalbumin
      to-creatinine ratio (malb/Cr) were examined. We also assessed the association
      between urine parameters and current age, gestational age, birth weight, and
      predictors of renal injury. Follow-up data were analyzed in 43 subjects 4-6 years
      later. RESULTS: Ninety percent of subjects had at least one tubular dysfunction.
      Frequency of elevated values was NAG/Cr 77.5%, UA/Cr 54.1%, beta2m/Cr 38.2%,
      malb/Cr 30.4%, Ca/Cr 21.5%, and glu/Cr 20.5%. There were significant negative
      correlations between the current age and Ca/Cr, NAG/Cr, glu/Cr, and UA/Cr,
      suggesting tubular function maturation. Urine beta2M/Cr and glu/Cr were
      negatively correlated with the gestational age. There were significant
      associations between elevated glu/Cr and asphyxia or neonatal acute kidney
      injury, and elevated NAG/Cr and indomethacin use, although these were not
      confirmed by multivariate analysis. At follow-up, the frequency of elevated
      NAG/Cr, glu/Cr, UA/Cr, and malb/Cr was reduced but that of elevated Ca/Cr,
      IgG/Cr, and beta2m/Cr remained similar or increased. CONCLUSION: Tubular
      dysfunction is common in ELBW survivors. Some abnormalities resolved with age
      while some remained persistent or even increased.

PMID- 30238384
TI  - Clinical outcomes of patients with hollow viscous injuries after a blunt
      abdominal trauma: the influence of diagnostic and therapeutic delay and the
      predictive role of BIPS.

PMID- 30238385
TI  - The role of emergency medical service providers in the decision-making process of
      prehospital trauma triage.
AB  - PURPOSE: Severely injured patients should be treated at higher-level trauma
      centres, to improve chances of survival and avert life-long disabilities.
      Emergency medical service (EMS) providers must try to determine injury severity
      on-scene, using a prehospital trauma triage protocol, and decide the most
      appropriate type of trauma centre. The objective of this study is to investigate
      the role of EMS provider judgment in the prehospital triage process of trauma
      patients, by analysing the compliance rate to the protocol and administering a
      questionnaire among EMS providers. METHODS: All trauma patients transported to a
      trauma centre in two different regions of the Netherlands were analysed.
      Compliance rate was based on the number of patients meeting the triage criteria
      and transported to the corresponding level trauma centre. The questionnaire was
      administered among EMS providers. Descriptive statistics were used to analyse the
      data. RESULTS: For adult patients, the compliance rate to the level I criteria of
      the triage protocol was 72% in Central Netherlands and 42% in Brabant. For
      paediatric patients, this was 63% and 38% in Central Netherlands and Brabant,
      respectively. The judgment on injury severity was mostly based on the injury-type
      criteria. Additionally, the distance to a level I trauma centre influenced the
      decision for destination facility in the Brabant region. CONCLUSION: The
      compliance rate varied between regions. Improvement of prehospital trauma triage
      depends on the accuracy of the protocol and compliance rate. A new protocol,
      including EMS provider judgment, might be the key to improvement in the
      prehospital trauma triage quality.

PMID- 30238382
TI  - Fibromyalgia and small fiber neuropathy: the plot thickens!
AB  - Several groups of investigators have described the presence of small fiber
      neuropathy in fibromyalgia patients. This writing discusses how this new finding
      could renovate fibromyalgia concept, diagnosis, and treatment. Predominant
      rheumatology thinking proposes fibromyalgia as a "centralized pain syndrome." An
      alternative hypothesis views fibromyalgia as a stress-related dysautonomia with
      neuropathic pain features. Dorsal root ganglia may be the key autonomic
      nociceptive short-circuit sites. The recent recognition of small fiber neuropathy
      in a large subgroup of fibromyalgia patients reinforces the dysautonomia
      neuropathic hypothesis and validates fibromyalgia pain. These new findings
      support fibromyalgia as a primarily neurological entity, nevertheless,
      rheumatologist will likely remain the best equipped specialist to diagnose
      fibromyalgia and differentiate it from other multi-symptomatic rheumatic
      syndromes. Skin biopsy and corneal confocal microscopy will probably become
      useful fibromyalgia diagnostic tests. Dorsal root ganglia sodium channel blockers
      are potential fibromyalgia analgesic medications. Subgroups of young girls with
      "autoimmune neuropathic fibromyalgia" may respond to immunoglobulin therapy.
      Multimodal intervention directed to regain autonomic nervous system resilience
      will likely remain the cornerstone for fibromyalgia therapy.

PMID- 30238386
TI  - Surgical Burden of Musculoskeletal Conditions in Low- and Middle-Income
      Countries.
AB  - BACKGROUND: The burden of musculoskeletal conditions is growing worldwide. In low
      and middle-income countries (LMIC), the burden cannot be fully estimated, due to
      paucity of credible data. Further, no attempt has been made so far to estimate
      surgical burden of musculoskeletal conditions. This is a difficult task and
      accurate estimation of what would constitute surgical burden out of the total
      musculoskeletal burden in LMIC is not possible, due to number of constraints.
      METHODS: This review looks at current understanding of the musculoskeletal
      conditions, that can be measured in LMIC and the limitations based on previous
      studies and past global burden of diseases estimates. RESULTS: An attempt has
      been made to identify major conditions where a range of surgical burden can be
      predicted. CONCLUSION: We conclude that there is huge scope for improvement in
      the current surveillance mechanism of surgical procedures undertaken for
      musculoskeletal conditions in LMIC so that the surgical burden can be more
      accurately predicted. Unless this burden can be highlighted, the attention to
      these conditions in LMIC will be limited.

PMID- 30238387
TI  - Trauma in the Elderly: Demographic Trends (1995-2014) in a Major New Zealand
      Trauma Centre.
AB  - BACKGROUND: Population studies have confirmed an increase in the proportion of
      elderly patients (>=65 years of age), and this could be expected to be reflected
      in trauma admissions and outcomes. This study aims to investigate the demographic
      trends for elderly patients admitted following trauma to Auckland City Hospital
      (ACH) and their outcomes. MATERIALS AND METHODS: The ACH Trauma Database was
      searched from 1995 to 2014, and data including date of admission, injury cause,
      age, sex, mortality, Injury Severity Score (ISS), Intensive Care Unit (ICU) stay
      and length of stay (LOS) were extracted. RESULTS: A total of 26,882 patients were
      identified, with 4428 patients >=65 years of age admitted following trauma. In
      the mid-1990s between 200 and 250 trauma patients >=65 years were admitted to ACH
      annually. This has increased to >400 in 2014 and now represents >20% of all
      admissions. Females are over represented (61.7%) in those >=65 years (vs. 29.4%
      in < 65 years, p < 0.001), and falls are the greatest cause of admission for
      trauma in those >=65 years at 72% (vs. 36.9% in those < 65 years, p < 0.001).
      Elderly trauma patients are more than twice as likely to die (5.6% vs. 2.3%, p <
      0.001) compared with trauma patients < 65 years despite an identical median ISS
      of 4 (p = 0.86). Furthermore, of those >=65 years, 2.2% died of minor/moderate
      trauma (ISS <= 15) versus only 0.12% for those < 65 years confirming the
      complexities of ageing physiology in a trauma setting. Until 2003, mortality from
      trauma in elderly patients closely paralleled the rate of severe trauma
      admissions (ISS >= 16), but after 2003, despite a steady increase in severe
      trauma in this cohort, mortality rates have fallen. CONCLUSIONS: Elderly patients
      bring with them a greater burden of co-morbidities, and trauma admission of
      elderly patients has almost doubled over 20 years, including severe trauma (ISS
      >= 16), but despite this mortality has decreased. Integration of services into
      the new ACH in 2003 as well as improving trauma and medical care may be possible
      explanations. Further resources will be required to meet service demand, along
      with consideration of strategies to integrate multi-disciplinary care and
      consolidate trauma management for this vulnerable patient group.

PMID- 30238388
TI  - Alterations in the Serotonin and Dopamine Pathways by Cystathionine Beta Synthase
      Overexpression in Murine Brain.
AB  - Cystathionine beta synthase (CBS) is one of the 225 genes on chromosome 21 (HSA
      21) that are triplicated in persons with trisomy 21 (Down syndrome). Although
      most triplicate HSA21 genes have their orthologous genes on murine chromosome 16,
      the murine ortholog of hCBS is on murine chromosome 17 and thus is not present in
      the well-studied Ts65Dn mouse model of trisomy 21. Persons with trisomy 21 (T21)
      present deficits in neurotransmission and exhibit early brain aging that can
      partially be explained by monoamine neurotransmitter alterations. We used
      transgenic mice for the hCBS gene, which overexpress the CBS protein in various
      brain regions, to study if CBS overexpression induces modifications in the
      monoamine neurotransmitters in the hypothalamus, thalamus, hippocampus, and
      striatum from transgenic and control female and male mice aged 3-4 months and 11
      12 months. Sex, age, and brain area each influenced neurotransmitter levels.
      Briefly, the serotonin pathway was modified by CBS overexpression in various
      brain areas in female mice but not in male mice. The dopamine pathway was
      modified in brain regions according to sex and age. These results may allow us to
      better understand the role of the transsulfuration pathway and especially CBS
      overexpression in the metabolism of biogenic amines and the catecholamine
      catabolism in persons with trisomy 21.

PMID- 30238389
TI  - Modeling Alzheimer's Disease by Induced Pluripotent Stem Cells Carrying APP D678H
      Mutation.
AB  - Alzheimer's disease (AD), probably caused by abnormal accumulation of beta
      amyloid (Abeta) and aberrant phosphorylation of tau, is the most common cause of
      dementia among older people. Generation of patient-specific neurons by induced
      pluripotent stem cell (iPSC) technology facilitates exploration of the disease
      features in live human neurons from AD patients. In this study, we generated
      iPSCs from two familial AD patients carrying a heterozygous D678H mutation in the
      APP gene (AD-iPSCs). The neurons derived from our AD-iPSCs demonstrated aberrant
      accumulation of intracellular and secreted Abeta42 and Abeta40, reduction of
      serine 9 phosphorylation in glycogen synthase kinase 3beta (GSK3beta)
      hyperphosphorylation of threonine 181 and serine 396 in tau protein, impaired
      neurite outgrowth, downregulation of synaptophysin, and increased caspase 1
      activity. The comparison between neurons derived from a sibling pair of wild-type
      and mutated iPSCs successfully recapitulated these AD phenotypes. Treatment with
      indole compound NC009-1 (3-((1H-Indole-3-yl)methyl)-4-(2-nitrophenyl)but-3-en-2
      one), a potential Abeta aggregation reducer, normalized the Abeta levels and
      GSK3beta and tau phosphorylation, attenuated caspase 1 activity, and improved
      neurite outgrowth in AD-iPSC-derived neurons. Thus, APP D678H iPSCs-derived
      neurons recapitulate the cellular characteristics relevant to AD and enable
      exploration of the underlying pathogenesis and therapeutic strategies for AD.

PMID- 30238390
TI  - Visualization of the Breakdown of the Axonal Transport Machinery: a Comparative
      Ultrastructural and Immunohistochemical Approach.
AB  - Axonal damage is a major factor contributing to disease progression in multiple
      sclerosis (MS) patients. On the histological level, acute axonal injury is most
      frequently analyzed by anti-amyloid precursor protein immunohistochemistry. To
      what extent this method truly detects axonal injury, and whether other proteins
      and organelles are as well subjected to axonal transport deficits in demyelinated
      tissues is not known. The aim of this study was to correlate ultrastructural
      morphology with the immunohistochemical appearance of acute axonal injury in a
      model of toxin-induced oligodendrocyte degeneration. C57BL/6J mice were
      intoxicated with 0.25% cuprizone to induce demyelination. The corpus callosum was
      investigated by serial block-face scanning electron microscopy (i.e., 3D EM),
      immunohistochemistry, and immunofluorescence microscopy. Brain tissues of
      progressive MS patients were included to test the relevance of our findings in
      mice for MS. Volumes of axonal swellings, determined by 3D EM, were comparable to
      volumes of axonal spheroids, determined by anti-APP immunofluorescence stains.
      Axonal swellings were present at myelinated and non-myelinated axonal internodes.
      Densities of amyloid precursor protein (APP)+ spheroids were highest during
      active demyelination. Besides APP, vesicular glutamate transporter 1 and
      mitochondrial proteins accumulated at sites of axonal spheroids. Such
      accumulations were found as well in lesions of progressive MS patients. In this
      correlative ultrastructural-immunohistochemical study, we provide strong evidence
      that breakdown of the axonal transport machinery results in focal accumulations
      of mitochondria and different synaptic proteins. We provide new marker proteins
      to visualize acute axonal injury, which helps to further understand the complex
      nature of axonal damage in progressive MS.

PMID- 30238391
TI  - Analysis of ocular inflammation in anterior chamber-involving uveitis using swept
      source anterior segment OCT.
AB  - PURPOSE: To evaluate the utility of swept-source (SS) optical coherence
      tomography (OCT) to objectively analyze the degree of anterior chamber (AC)
      inflammation. METHODS: Thirty-eight eyes of 32 patients with uveitis and 20
      control eyes were enrolled. SS OCT B-scans were obtained, and the number of cells
      in the B-scans was counted using two methods: (1) manual grading by Point Picker
      plug-in of Image J ( http://bigwww.epfl.ch/thevenaz/pointpicker/ ) and (2)
      automated grading by the Image J Particle Analysis algorithm (
      http://imagej.net/Particle_Analysis ). The automated and manual AC cell counts
      were correlated with the Standardization of Uveitis Nomenclature score. RESULTS:
      The average numbers of AC inflammatory cells counted by the automated method were
      8 +/- 4.0, 18 +/- 3.0, 42 +/- 14.0, 81 +/- 32.0, 117 +/- 57.0, and 275 +/- 67.0
      cells/mm2 for grades 0, 0.5 + , 1 + , 2 + , 3 + , and 4 + , respectively. For the
      same clinical categories, the average manual cell counts were 6 +/- 4.0, 18 +/-
      3.0, 34 +/- 14.0, 72 +/- 32.0, 92 +/- 43.0, and 168 +/- 65.0 cells/mm2,
      respectively. Zero cells were detected in the AC of healthy eyes. The automated
      and manual methods were highly correlated (R = 0.98, p < 0.001) and showed good
      correlation with the clinical grading (R = 0.88, p < 0.001). A mean AC particle
      size of 117.4 +/- 108.8 MUm was obtained by the automated method. CONCLUSIONS:
      Quantification of the AC cells imaged by SS AS-OCT shows good correlation with
      categorical clinical severity assessments in uveitis eyes. This approach may
      provide a more objective method for monitoring uveitis and response to uveitis
      therapy.

PMID- 30238392
TI  - Design and synthesis of novel 6-substituted quinazoline-2-thiols.
AB  - A novel design and efficient protocol for the synthesis of new class of 6
      substituted quinazoline-2-thiols is reported. The derivatization of the
      thioquinazolines is achieved in a strategic manner using 2-aminobenzylamine. The
      functionalization of the aniline followed by construction of the heterocyclic
      ring provides a facile way to synthesize these bifunctional quinazolines.

PMID- 30238393
TI  - Synthesis of deuterium-enriched sorafenib derivatives and evaluation of their
      biological activities.
AB  - Deuterium substitution has been widely known that can improve the pharmacokinetic
      profiles due to isotope effect. Herein, a series of deuterated sorafenib
      derivatives have been synthesized and characterized by 1H NMR, 13C NMR and MS.
      Their antitumor activities were evaluated in vitro against human hepatoma cell
      line HepG2 and human cervical carcinoma cell line HeLa. The LogP values were
      detected by high-performance liquid chromatography. Subsequently, the metabolic
      stability and pharmacokinetics study were assessed in vitro and in vivo.

PMID- 30238394
TI  - Facile access to new pyrido[2,3-d]pyrimidine derivatives.
AB  - In this report, a facile, operationally, simple and highly efficient one-pot
      coupling of 2,6-diaminopyrimidin-4(3H)-one and ethyl-2,4-dioxo-4-phenylbutanoate
      derivatives is reported. This method afforded a novel series of ethyl-2-amino-3,4
      dihydro-4-oxo-5-phenyl pyrido[2,3-d] pyrimidine-7-carboxylate heterocycle
      derivatives in high yields under refluxing AcOH.

PMID- 30238395
TI  - Survey of the management of perioperative bridging of anticoagulation and
      antiplatelet therapy in neurosurgery.
AB  - BACKGROUND: A growing number of patients on anticoagulation or antiplatelet
      therapy (APT) are planned for elective surgery. The management of perioperative
      anticoagulation and APT is challenging because it must balance the risk of
      thromboembolism and bleeding, and specific recommendations for the management of
      bridging in neurosurgical patients are lacking. We surveyed German neurosurgical
      centers about their management of perioperative bridging of anticoagulation and
      APT to provide an overview of the current bridging policy. METHOD: From April to
      August 2016, all German neurosurgical departments were invited to participate in
      the survey. We used SurveyMonkey to compose ten questions and to conduct the
      survey, and we defined three different approaches for the perioperative
      management of patients on a preexisting medication: medication will be
      discontinued (A) with perioperative "bridging" and (B) without perioperative
      bridging, or (C) medication will be continued perioperatively. RESULTS: Out of
      141 respondents, 84 (60%) partially and 77 (55%) fully completed the
      questionnaire. No defined policy for the perioperative management of
      anticoagulation and APT was established in 60.7% (51/84) of participating
      centers. The perioperative management of anticoagulation and APT varied widely
      among different centers in all items of the questionnaire; for example, in the
      group of patients at high risk for thromboembolism, acetylsalicylic acid was
      discontinued in 22%, bridged in 35%, and continued in 35% of centers.
      CONCLUSIONS: There is significant uncertainty regarding the management of
      perioperative bridging of anticoagulation and APT in neurosurgery because of a
      lack of prospective and limited retrospective data.

PMID- 30238397
TI  - Gene Therapy for Heart Failure: New Perspectives.
AB  - PURPOSE OF REVIEW: The current knowledge of pathophysiological and molecular
      mechanisms responsible for the genesis and development of heart failure (HF) is
      absolutely vast. Nonetheless, the hiatus between experimental findings and
      therapeutic options remains too deep, while the available pharmacological
      treatments are mostly seasoned and display limited efficacy. The necessity to
      identify new, non-pharmacological strategies to target molecular alterations led
      investigators, already many years ago, to propose gene therapy for HF. Here, we
      will review some of the strategies proposed over the past years to target major
      pathogenic mechanisms/factors responsible for severe cardiac injury developing
      into HF and will provide arguments in favor of the necessity to keep alive
      research on this topic. RECENT FINDINGS: After decades of preclinical research
      and phases of enthusiasm and disappointment, clinical trials were finally
      launched in recent years. The first one to reach phase II and testing gene
      delivery of sarcoendoplasmic reticulum calcium ATPase did not yield encouraging
      results; however, other trials are ongoing, more efficient viral vectors are
      being developed, and promising new potential targets have been identified. For
      instance, recent research is focused on gene repair, in vivo, to treat heritable
      forms of HF, while strong experimental evidence indicates that specific microRNAs
      can be delivered to post-ischemic hearts to induce regeneration, a result that
      was previously thought possible only by using stem cell therapy. Gene therapy for
      HF is aging, but exciting perspectives are still very open.

PMID- 30238398
TI  - Improving Provider Adherence to Guideline Recommendations in Heart Failure.
AB  - PURPOSE OF REVIEW: Heart failure clinical practice guidelines are fundamental and
      serve as framework for providers to deliver evidence-based care that correlates
      with enhanced patient outcomes. However, adherence, particularly to guideline
      directed medical therapy, remains suboptimal for a multitude of reasons. RECENT
      FINDINGS: Despite robust clinical trials, updated guidelines and an expert
      consensus statement from American Heart Association, American College of
      Cardiology, and Heart Failure Society of America registry data signal that heart
      failure patients do not receive appropriate pharmacotherapy and may receive an
      intracardiac device without prior initiation or optimization of medical therapy.
      Strategies to improve provider adherence to heart failure guidelines include
      multidisciplinary models and appropriate referral and care standardization. These
      approaches can improve morbidity, mortality, and quality of life in HF patients.

PMID- 30238399
TI  - Update of the ICUD-SIU International Consultation on Bladder Cancer 2018: urinary
      diversion.
AB  - PURPOSE: To provide a comprehensive overview and update of the joint consultation
      of the International Consultation on Urological Diseases (ICUD) and Societe
      Internationale d'Urologie on Bladder Cancer Urinary Diversion (UD). METHODS: A
      detailed analysis of the literature was conducted reporting on the different
      modalities of UD. For this updated publication, an exhaustive search was
      conducted in PubMed for recent relevant papers published between October 2013 and
      August 2018. Via this search, a total of 438 references were identified and 52 of
      them were finally eligible for analysis. An international, multidisciplinary
      expert committee evaluated and graded the data according to the Oxford System of
      Evidence-based Medicine. RESULTS: The incidence of early complications has been
      reported retrospectively in the range of 20-57%. Unfortunately, only a few
      randomized controlled studies exist within the field of UD. Consequently, almost
      all studies used in this report are of level 3-4 evidence including expert
      opinion based on "first principles" research. CONCLUSIONS: Complications rates
      overall following RC and UD are significant, and when strict reporting criteria
      are incorporated, they are much higher than previously published. Complications
      can occur up to 20 years after surgery, emphasizing the need for lifelong follow
      up. Progress has been made to prevent complications implementing robotic surgery
      and fast track protocols. Preoperative patient information, patient selection,
      surgical techniques, and careful postoperative follow-up are the cornerstones to
      achieve good results.

PMID- 30238401
TI  - SIU-ICUD recommendations on bladder cancer: systemic therapy for metastatic
      bladder cancer.
AB  - The SIU (Societe Internationale d'Urologie)-ICUD (International Consultation on
      Urologic Diseases) working group on systemic therapy for metastatic bladder
      cancer has summarized the most recent findings on the aforementioned topic and
      came to conclusions and recommendations according to the evidence published. In
      Europe and the United States, treatment for metastatic UC has changed a great
      deal recently, mainly involving a move from chemotherapy to immune checkpoint
      blockers. This is particularly true in platinum-refractory disease, where
      supportive randomized data exist. Five checkpoint blockers have been approved in
      this setting by the FDA: avelumab, atezolizumab, durvalumab, nivolumab, and
      pembrolizumab. Nivolumab, pembrolizumab, and atezolizumab have been approved in
      Europe.

PMID- 30238402
TI  - Folic Acid-Containing Dietary Supplement Consumption and Risk of Cardiovascular
      Diseases in Rheumatoid Arthritis Patients: NHANES 1999-2014.

PMID- 30238400
TI  - Novel laser positioning navigation to aid puncture during percutaneous
      nephrolithotomy: a preliminary report.
AB  - PURPOSE: Accurate puncture of the renal collecting system is crucial to the
      success of percutaneous nephrolithotomy and presents a technical challenge for
      urologists. Here, we introduced the Surgical Approach Visualization and
      Navigation (SAVN) system, a novel navigation system to assist puncture and reduce
      intraoperative radiation. MATERIALS AND METHODS: Twenty kidneys of 10 cadavers
      were randomly divided into two groups for renal calyx puncture. In the control
      group, traditional fluoroscopy was used for guidance, while SAVN system was used
      in the experimental group. Puncture duration, number of puncture attempts, total
      number of intraoperative fluoroscopies, and number of fluoroscopies during the
      puncture procedure were recorded. RESULTS: The puncture duration was 14.2 +/- 2.5
      s in SAVN group and 48.3 +/- 7.1 s in conventional group (P < 0.05). One puncture
      attempt was needed for successful puncture in SAVN group, while more than one in
      conventional group (P = 0.28). The total number of intraoperative fluoroscopies
      was 3.3 +/- 1.0 in SAVN group and 14.5 +/- 3.1 in control group (P < 0.05),while
      the number of fluoroscopies during the puncture procedure was 0 and 11.2 +/- 2.4,
      respectively (P < 0.05). CONCLUSIONS: The novel SAVN system has a simplified
      structure and is easy to use. It can be used to successfully assist with puncture
      of the renal calyx, thus reducing puncture duration and radiation dose.

PMID- 30238403
TI  - Early Medicaid Expansions and Drug Overdose Mortality in the USA: a Quasi
      experimental Analysis.

PMID- 30238404
TI  - Race and Hepatitis C Care Continuum in an Underserved Birth Cohort.
AB  - BACKGROUND: Birth cohort screening is recommended for hepatitis C virus (HCV) and
      underserved populations are disproportionally affected by HCV. Little is known
      about the influence of race on the HCV care continuum in this population.
      OBJECTIVE: To assess the cascade of HCV care in a large racially diverse and
      underserved birth cohort. DESIGN: Retrospective cohort study using electronic
      medical record data abstracted until August 31, 2017. PATIENTS: 34,810 patients
      born between 1945 and 1965 engaged in primary care between October 1, 2014, and
      October 31, 2016, within the safety-net clinics of the San Francisco Health
      Network. MAIN MEASURES: Rate of hepatitis C testing, hepatitis C treatment, and
      response to therapy. RESULTS: Cohort characteristics were as follows: median age
      59 years, 57.6% male, 25.5% White (20.6% Black, 17.7% Latino, 33.0% Asian/Pacific
      Islander (API), 2% other), and 32.6% preferred a non-English language. 99.7% had
      an HCV test (95.4% HCV antibody, 4.3% HCVRNA alone). Among HCV antibody-positive
      patients (N = 4587), 22.9% were not tested for confirmatory HCVRNA. Among viremic
      patients (N = 3673), 20.8% initiated HCV therapy, 90.6% achieved sustained
      virologic response (SVR) and 8.1% did not have a SVR test. HCV screening and
      treatment were highest in APIs (98.7 and 34.7% respectively; p < 0.001). Blacks
      had the highest chronic HCV rate (22.2%; p < 0.001). Latinos had the lowest SVR
      rate (81.3%; p = 0.01). On multivariable analysis, API race (vs White, OR 1.20; p
      = 0.001), presence of HIV co-infection (OR 1.58; p = 0.02), presence of chronic
      kidney disease (OR 0.47; p < 0.001), English (vs non-English) as preferred
      language (OR 0.54; p = 0.002), ALT (OR 0.39 per doubling; p < 0.001), and HCVRNA
      (OR 0.83 per 10-fold increase; p < 0.001) were associated with HCV treatment.
      CONCLUSIONS: Despite near-universal screening, gaps in active HCV confirmation,
      treatment, and verification of cure were identified and influenced by race.
      Tailored interventions to engage and treat diverse and underserved populations
      with HCV infection are needed.

PMID- 30238405
TI  - Hospitalized Patients' Knowledge of Care: a Systematic Review.
AB  - BACKGROUND: Patients' comprehension of their medical conditions is fundamental to
      patient-centered care. Hospitalizations present opportunities to educate patients
      but also challenges to patient comprehension given the complexity and rapid pace
      of clinical care. We conducted a systematic review of the literature to
      characterize the current state of inpatients' knowledge of their hospitalization,
      assess the methods used to determine patient comprehension, and appraise the
      effects of interventions on improving knowledge. METHODS: We searched MEDLINE,
      EMBASE, and the Cochrane Library for articles published from January 1, 1995
      through December 11, 2017. Eligible studies included patients under inpatient or
      observation status on internal medicine, family medicine, or neurology services.
      We extracted study characteristics (author, year, country, study design, sample
      size, patient characteristics, methods, intervention, primary endpoints, results)
      in a standardized fashion. The quality of observational studies was assessed
      using the NIH Quality Assessment Tool for Observation Cohort and Cross-Sectional
      Studies and the quality of interventional studies was assessed using adapted EPOC
      criteria from the Cochrane Collaboration. RESULTS: Twenty-eight studies met the
      criteria for inclusion, including 17 observational studies and 11 interventional
      studies. Patient knowledge of all aspects of their hospitalization was poor and
      patients often overestimated their knowledge. Older patients and those with lower
      education levels were more likely to have poorer knowledge. Intervention methods
      varied, but generally showed improvements in patient knowledge. Few
      interventional studies assessed the effect on health behaviors or outcomes and
      those that did were often underpowered. DISCUSSION: Clinicians should be aware
      that comprehension is often poor among hospitalized patients, especially in those
      with lower education and advanced age. Our results are limited by overall poor
      quality of interventional studies. Future research should use objective,
      standardized measures of patient comprehension and interventions should be
      multifaceted in approach, focusing on knowledge improvement while also addressing
      other factors influencing outcomes.

PMID- 30238407
TI  - The Masked ABR (mABR): a New Measurement Method for the Auditory Brainstem
      Response.
AB  - The auditory brainstem response (ABR) is relatively non-invasive, and in many
      species, the only practical way to assess auditory sensitivity. The two main
      methods for measuring ABR are using either transients or tone bursts as a
      stimulus. The transient stimulus produces strong neural responses that contain no
      frequency information. In contrast, tone bursts stimulate only a small part of
      the auditory system, eliciting weaker neural responses but supplying frequency
      information. Furthermore, short tone bursts become less and less frequency
      specific with increasing stimulus wavelength, making them unsuitable for testing
      low-frequency hearing. Here, we develop a method that can measure sensitivity to
      both low and high-frequency stimuli. The method is based on masking of a
      transient response by long-duration sinusoids. The measurement system is
      developed as a highly portable system that runs on battery power. It has been
      used in a variety of animals in our lab and in the field, including squid (Mooney
      et al. in J Exp Biol 213: 3748-3759, 2010), lungfish (Christensen-Dalsgaard et
      al. in J Neurophys 105: 1992-2004, 2011b), alligators (Bierman et al. in J Exp
      Biol 217: 1094-1107, 2014), and mink (Brandt et al. in J Exp Biol 216: 3542-3550,
      2013). Here, we present data recorded from Tokay geckos and compare the results
      with tone burst ABR measurements. This method produces results comparable to tone
      burst stimulations at higher frequencies (above 1 kHz) but has several
      advantages: it is relatively insensitive to fluctuations in neural signal level,
      it allows measurements at very low frequencies, it allows constant monitoring of
      the state of the animal, and can be used to measure directional hearing.

PMID- 30238396
TI  - Targeted Therapies for Autoimmune Bullous Diseases: Current Status.
AB  - Autoimmune bullous skin disorders are rare but meaningful chronic inflammatory
      diseases, many of which had a poor or devastating prognosis prior to the advent
      of immunosuppressive drugs such as systemic corticosteroids, which down-regulate
      the immune pathogenesis in these disorders. Glucocorticoids and adjuvant
      immunosuppressive drugs have been of major benefit for the fast control of most
      of these disorders, but their long-term use is limited by major side effects such
      as blood cytopenia, osteoporosis, diabetes mellitus, hypertension, and
      gastrointestinal ulcers. In recent years, major efforts were made to identify key
      elements in the pathogenesis of autoimmune bullous disorders, leading to the
      identification of their autoantigens, which are mainly located in desmosomes
      (pemphigus) and the basement membrane zone (pemphigoids). In the majority of
      cases, immunoglobulin G, and to a lesser extent, immunoglobulin A autoantibodies
      directed against distinct cutaneous adhesion molecules are directly responsible
      for the loss of cell-cell and cell-basement membrane adhesion, which is
      clinically related to the formation of blisters and/or erosions of the skin and
      mucous membranes. We describe and discuss novel therapeutic strategies that
      directly interfere with the production and regulation of pathogenic
      autoantibodies (rituximab), their catabolism (intravenous immunoglobulins), and
      their presence in the circulation and extravascular tissues such as the skin
      (immunoadsorption), leading to a significant amelioration of disease. Moreover,
      we show that these novel therapies have pleiotropic effects on various
      proinflammatory cells and cytokines. Recent studies in bullous pemphigoid suggest
      that targeting of immunoglobulin E autoantibodies (omalizumab) may be also
      beneficial. In summary, the introduction of targeted therapies in pemphigus and
      pemphigoid holds major promise because of the high efficacy and fewer side
      effects compared with conventional global immunosuppressive therapy.

PMID- 30238406
TI  - Correction to: Some theoretical insights into the hologenome theory of evolution
      and the role of microbes in speciation.
AB  - The original version of this article unfortunately contained a mistake.

PMID- 30238408
TI  - Novel tumor suppressor SPRYD4 inhibits tumor progression in hepatocellular
      carcinoma by inducing apoptotic cell death.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer
      associated deaths worldwide. Although recent studies have proposed different
      biomarkers for HCC progression and therapy resistance, a better understanding of
      the molecular mechanisms underlying HCC progression and recurrence, as well as
      the identification of molecular markers with a higher diagnostic accuracy, are
      necessary for the development of more effective clinical management strategies.
      Here, we aimed to identify novel players in HCC progression. METHODS: SPRYD4 mRNA
      and protein expression analyses were carried out on a normal liver-derived cell
      line (HL-7702) and four HCC-derived cell lines (HepG2, SMMC7721, Huh-7, BEL-7402)
      using qRT-PCR and Western blotting, respectively. Cell proliferation Cell
      Counting Kit-8 (CCK-8) assays, protein expression analyses for apoptosis markers
      using Western blotting, and Caspase-Glo 3/7 apoptosis assays were carried out on
      the four HCC-derived cell lines. Expression comparison, functional annotation,
      gene set enrichment, correlation and survival analyses were carried out on
      patient data retrieved from the NCBI Gene module, the NCBI GEO database and the
      TCGA database. RESULTS: Through a meta-analysis we found that the expression of
      SPRYD4 was downregulated in primary HCC tissues compared to non-tumor tissues. We
      also found that the expression of SPRYD4 was downregulated in HCC-derived cells
      compared to normal liver-derived cells. Subsequently, we found that the
      expression of SPRYD4 was inversely correlated with a gene signature associated
      with HCC cell proliferation. Exogenous SPRYD4 expression was found to inhibit HCC
      cell proliferation by inducing apoptotic cell death. We also found that SPRYD4
      expression was associated with a good prognosis and that its expression became
      downregulated when HCCs progressed towards more aggressive stages and higher
      grades. Finally, we found that SPRYD4 expression may serve as a biomarker for a
      good overall and relapse-free survival in HCC patients. CONCLUSIONS: Our data
      indicate that a decreased SPRYD4 expression may serve as an independent predictor
      for a poor prognosis in patients with HCC and that increased SPRYD4 expression
      may reduce HCC growth and progression through the induction of apoptotic cell
      death, thereby providing a potential therapeutic target.

PMID- 30238410
TI  - The role of oxidative stress as a risk factor for rupture of posterior inferior
      cerebellar artery aneurysms.
AB  - Cerebral aneurysm affects 2-5% of the population and posterior inferior
      cerebellar artery (PICA) aneurysms account for 1-3% of all intracranial
      aneurysms. Oxidative stress is known to contribute to the progression of
      cerebrovascular disease and it may be increased by inflammation, a key
      contributor to cerebral aneurysm development and rupture. The aim of this study
      was to examine the role of overall oxidative stress as a risk factor for rupture
      of PICA aneurysms. This study included 29 patients with PICA aneurysms: 18
      ruptured and 11 unruptured. We determined catalase, malondialdehyde,
      myeloperoxidase and carbonyl groups in homogenates of excised aneurysm tissue
      after surgery and plasma levels of C reactive protein and fibrinogen. The
      patient's age and sex, size of aneurysms, multiplicity, history of previous
      subarachnoidal hemorrhage (SAH) and risk factors for oxidative stress such as
      hypertension and smoking were compared between unruptured and ruptured aneurysms.
      Maximal diameter and SAH history were independent predictors for aneurysm
      rupture. Activity of catalase was decreased while activity of myeloperoxidase,
      levels of malondialdehyde, carbonyl groups in aneurismal tissue and plasma levels
      of C reactive protein and fibrinogen were increased in patients with ruptured
      aneurysms. Plasma levels of C reactive protein and fibrinogen showed positive
      correlation with myeloperoxidase, malondialdehyde, carbonyl groups and PHASES
      score and negative correlation with catalase. These findings suggest that
      oxidative stress may contribute importantly to rupture of PICA aneurysms and
      plasma levels of C reactive protein and fibrinogen correlate with oxidative
      stress markers in tissue.

PMID- 30238409
TI  - Perceived Fatigability: Utility of a Three-Dimensional Dynamical Systems
      Framework to Better Understand the Psychophysiological Regulation of Goal
      Directed Exercise Behaviour.
AB  - A three-dimensional framework of perceived fatigability emphasises the need to
      differentiate between the qualitatively distinct inputs of sensory
      discriminatory, affective-motivational and cognitive-evaluative processes that
      shape the perceptual milieu during prolonged endurance exercise. This article
      reviews the framework's utility to better understand how cause-effect
      relationships come to be and how perception-action coupling underpins pacing
      behaviour and performance fatigability. Preliminary evidence supports the
      hypotheses that perceived strain plays a primary role in trajectory regulation of
      pacing behaviour, core affect plays a primary and mediatory role in behavioural
      performance regulation, and the mindset shift associated with an action crisis
      plays a primary role in the intensity dependent volitional self-regulatory
      control of conflicting motivational drives. The constructs hypothesised to
      underpin perceived fatigability are systematically linked, context-dependent,
      constraint-based, distinguishable and show proportional continuous
      interdependency. They are further interrelated with dynamic changes in pacing
      behaviour, performance fatigability and physiological disturbance. Appropriate
      measurement selections for the subordinate constructs perceived physical strain,
      perceived mental strain, valence, arousal, action crisis and flow state are
      discussed. To better understand the non-proportional discontinuous effects of
      fatigue on discrete shifts in thought states and mindsets, non-linear dynamical
      systems theory is introduced as an unbiased overarching theory of governing
      principles in the temporal evolution of complex systems. This provides the
      opportunity to discuss the bio-psycho-social fatigue phenomenon from a dynamical
      and holistic perspective. The proposed framework offers a sophisticated
      alternative to the Gestalt concept of perceived exertion and comprehensively
      accounts for the psychophysiological processes that determine pacing behaviour
      and performance. It has the potential to enrich theory development and facilitate
      a deeper understanding of the psychophysiological regulation of goal-directed
      exercise behaviour.

PMID- 30238412
TI  - The anti-inflammatory effect of milk and dairy products on periodontal cells: an
      in vitro approach.
AB  - OBJECTIVE: Milk can reduce intestinal tissue damage in colitis models, and
      protects infants against necrotizing enterocolitis. However, whether milk can
      decrease inflammation related to peri-implantitis and oral mucosal dehiscence
      remains unclear. We therefore investigated whether or not milk and fermented by
      products have any anti-inflammatory effects on the cells of the oral cavity.
      MATERIAL AND METHODS: Human gingival fibroblasts and the human oral epithelial
      cell line HSC2 were exposed to pasteurized human milk, pasteurized cow's milk,
      dairy products, and powdered milk. An inflammatory response was then provoked
      with IL1 and TNFalpha. The expression changes of IL1, IL6, and IL8 were detected
      by reverse transcriptase PCR and immunoassay. RESULTS: We can report that
      pasteurized human milk and pasteurized cow's milk as well as yoghurt, buttermilk,
      sour milk, whey, and powdered milk can lower the expression of inflammatory
      cytokines in gingival fibroblasts being stimulated by IL1 and TNFalpha. A similar
      anti-inflammatory response to pasteurized milk and dairy products was observed
      with the human oral epithelial cell line HSC2. CONCLUSION: These data suggest
      that pasteurized and powdered milk, as well as fermented dairy products, display
      an anti-inflammatory effect on oral fibroblasts and oral epithelial cells.
      CLINICAL RELEVANCE: Our in vitro findings provide the scientific basis to extend
      this research towards testing the anti-inflammatory effects of milk in a pre
      clinical periodontitis and peri-implantitis model.

PMID- 30238413
TI  - Evaluation of the relationship between obturation length and presence of apical
      periodontitis by CBCT: an observational cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between length
      of root canal obturation (RCO) and the presence of apical periodontitis (AP) in
      different dental groups using cone-beam computed tomography (CBCT) analysis.
      MATERIALS AND METHODS: A total of 392 roots with canal treatment performed for
      more than 4 years were evaluated using CBCT. Distances from the apex to the tip
      of filling material were measured and classified as more than 2 mm short of the
      apex, approximately 1-2 mm short of the apex, at the apex, and beyond the apex.
      Odds ratio, confidence interval, and the chi2 test were used for statistical
      analyses. RESULTS: The frequency of AP was significantly greater in molars than
      in the other tooth groups (p < 0.05). Moreover, RCO that ended 1-2 mm short of
      the apex was associated with a lower prevalence of AP in molars and premolars (p
      < 0.05) and in anterior teeth (p < 0.1) when compared with RCO at the apex, more
      than 2 mm short of the apex, or beyond the apex. When the RCO reached the apex,
      there was no difference in the presence of AP among dental groups (p > 0.05).
      CONCLUSION: The length of RCOs can influence the presence of AP, with molars
      showing a higher prevalence. RCOs ending 1-2 mm short of the apex are associated
      with an absence of AP. CLINICAL RELEVANCE: The length of obturation is related to
      the presence of apical peridontitis and consequently to the success of endodontic
      treatment.

PMID- 30238411
TI  - Predicting membrane proteins and their types by extracting various sequence
      features into Chou's general PseAAC.
AB  - For many biological functions membrane proteins (MPs) are considered crucial. Due
      to this nature of MPs, many pharmaceutical agents have reflected them as
      attractive targets. It bears indispensable importance that MPs are predicted with
      accurate measures using effective and efficient computational models (CMs).
      Annotation of MPs using in vitro analytical techniques is time-consuming and
      expensive; and in some cases, it can prove to be intractable. Due to this
      scenario, automated prediction and annotation of MPs through CM based techniques
      have appeared to be useful. Based on the use of computational intelligence and
      statistical moments based feature set, an MP prediction framework is proposed.
      Furthermore, the previously used dataset has been enhanced by incorporating new
      MPs from the latest release of UniProtKB. Rigorous experimentation proves that
      the use of statistical moments with a multilayer neural network, trained using
      back-propagation based prediction techniques allows more thorough results.

PMID- 30238414
TI  - MTA and biodentine for primary teeth pulpotomy: a systematic review and meta
      analysis of clinical trials.
AB  - OBJECTIVE: This study aims to perform a systematic review and meta-analysis of
      clinical trials in order to evaluate the clinical and radiographic success rates
      of primary teeth pulpotomy performed with biodentine, when compared to MTA.
      METHODS: Search strategies were conducted in nine databases on August 5th, 2017,
      update on February 14th, 2018. Clinical articles were selected, which were in
      accordance with the inclusion and exclusion criteria and the research objective.
      They were analyzed by meta-analysis at three time points (6, 12, and 18 months).
      RESULTS: Out of the 233 publications initially identified, only 9 studies that
      fulfilled the inclusion criteria were included in the review. The 6-month overall
      clinical (RR = 0.99; 95% CI = 0.96-1.02, p = 0.92) and radiographic success rates
      (RR = 0.96; 95% CI = 0.92-1.00, p = 0.28) showed that biodentine vs. MTA did not
      differ statistically. The 12 and 18-month overall clinical success rates,
      respectively (RR = 1.01; 95% CI = 0.97-1.04, p = 0.77; RR = 0.98; 95% CI = 0.92
      1.05, p = 0.74) and radiographic success rates, respectively (RR = 0.97; 95% CI =
      0.92-1.02, p = 0.11; RR = 1.00; 95% CI = 0.91-1.10, p = 0.56) also showed that
      biodentine vs. MTA did not differ statistically. CONCLUSION: There is no
      superiority of one material over the other, MTA versus biodentine. CLINICAL
      RELEVANCE: This systematic review comparing the performance of biodentine in
      relation to the MTA when used in the pulpotomy technique in primary teeth.
      Although MTA is considered the gold standard material for pulpotomy procedures,
      it has some drawbacks (poor handling, staining potential, long setting time);
      thus, it is important to evaluate the clinical performance of other calcium
      silicate-based cements like biodentine that overcome this drawbacks.

PMID- 30238415
TI  - Treatment of buccal soft tissue dehiscence around single implant: 5-year results
      from a prospective study.
AB  - OBJECTIVES: The aim of this study is to report the 5-year outcomes of a coverage
      procedure of shallow maxillary soft tissue dehiscences, around single tissue
      level implants. MATERIAL AND METHODS: The original population consisted of 16
      patients presenting a single maxillary buccal implant soft tissue recession. A
      connective tissue graft, taken from the maxillary tuberosity, was inserted
      underneath a split-thickness envelope flap. After treatment, patients received
      individually tailored supportive periodontal therapy (SPT). RESULTS: Two patients
      were lost to follow-up, while one implant was removed due to peri-implantitis,
      before the final examination. At 5 years, complete implant soft tissue coverage
      was depicted in 8 out of 13 cases (62%). Mean soft tissue dehiscence coverage was
      86%. Patients' esthetic evaluation showed the persistency of high VAS scores.
      CONCLUSIONS: Treatment of buccal soft tissue dehiscence around single implant,
      followed by regular supportive therapy, resulted in good esthetic and functional
      results in the majority of patients. CLINICAL RELEVANCE: Within the limits of
      this study, the positive results suggest that the proposed technique may be a
      reliable option in selected cases.

PMID- 30238417
TI  - Longevity, effectiveness, safety, and impact on quality of life of low
      concentration hydrogen peroxides in-office bleaching: a randomized clinical
      trial.
AB  - OBJECTIVE: The study evaluated the longevity, effectiveness, safety, and impact
      on the oral health-related quality of life of in-office dental bleaching using
      low-concentration hydrogen peroxides. MATERIALS AND METHODS: Randomized,
      parallel, and double-blinded clinical trial was performed with 54 participants
      using 6% or 15% hydrogen peroxide (HP) in-office bleaching activated via hybrid
      LED/laser light. Tooth color was evaluated at baseline (T1), 1 week of bleaching
      (T2), 2 weeks of bleaching (T3) and 1 week (T4) and 6 months (T5) after finishing
      the bleaching using the Classical VitaTM scale and spectrophotometer. Tooth
      sensitivity and gingival irritation were measured with Visual Numeric Scale and
      Modified Gingival Index. The impact on quality of life was evaluated using the
      Oral Impact on Daily Performance. The data were analyzed using the Friedman, Mann
      Whitney, and McNemar tests (p < 0.05). RESULTS: The group HP15% presented
      significant color change (DeltaE) from T1 to T4 (p = 0.002) and T1 to T5 (p <
      0.001). Parameters L, a*, and b* differed significantly at T3, T4, and T5
      compared T1 for both groups. At 6-month follow-up, 57.1% of HP6 and 43.7% of
      HP15% participants migrated from B1 to a darker color. No significant differences
      were observed between the groups in tooth sensitivity, gingival irritation, or
      impact on quality of life. CONCLUSIONS: Both agents showed bleaching
      effectiveness, but HP15% presented greater color stability than HP6%, at 6-month
      follow-up. The agents showed low levels of tooth sensitivity, gingival
      irritation, and did not affect the oral health-related quality of life of the
      participants. CLINICAL RELEVANCE: Despite the greater presence of sensitivity
      during treatment compared with 6% hydrogen peroxide, 15% hydrogen peroxide
      demonstrated better bleaching effectiveness, and greater color stability at the
      end of bleaching and at 6-month follow-up. The use of 15% hydrogen peroxide
      presents more suitable results.

PMID- 30238416
TI  - Micro-invasive interventions for managing non-cavitated proximal caries of
      different depths: a systematic review and meta-analysis.
AB  - OBJECTIVES: The aim of this study was to further evaluate the caries-arresting
      effectiveness of micro-invasive interventions for non-cavitated proximal caries
      and analyze their efficacy for caries lesions of different depths. MATERIALS AND
      METHODS: Randomized clinical trials (RCTs) of micro-invasive interventions for
      non-cavitated proximal caries were included in this study. We searched the
      Cochrane Library, PubMed, Embase, and Web of Science on May 25, 2017, without
      restrictions. After duplicate study selection, data extraction, and risk of bias
      assessment, a meta-analysis of the odds ratios (OR) with 95% confidence intervals
      (95% CIs) and a publication bias analysis were conducted using Stata 12.0.
      RESULTS: After 2195 citations were screened, 8 citations of seven studies with
      follow-up periods from 12 to 36 months were included. The subgroup analysis
      showed that resin infiltration and resin sealant, but not glass ionomer cement
      (GIC), could reduce the caries progression rate (resin infiltration: OR = 0.15,
      95% CI 0.09 to 0.24; resin sealant: OR = 0.33, 95% CI 0.19 to 0.58; GIC: OR =
      0.13, 95% CI 0.01 to 2.65). Further analysis of their efficacies for caries
      lesions of different depths indicated that resin infiltration could arrest
      progression of enamel caries and caries around the enamel-dentin junction (EDJ)
      (enamel: OR = 0.05, 95% CI 0.01 to 0.35; EDJ: OR = 0.07, 95% CI 0.01 to 0.70).
      However, when the outer third of the dentin was involved, resin infiltration
      yielded significantly different results compared with the control group (OR =
      0.42, 95% CI 0.16 to 1.10). Resin sealant seemed to be ineffective regardless of
      the caries depth (enamel: OR = 0.62, 95% CI 0.13 to 3.00; EDJ: OR = 0.44, 95% CI
      0.09 to 2.15; dentin: OR = 0.43, 95% CI 0.07 to 2.63). CONCLUSIONS: Resin
      infiltration is effective in arresting the progression of non-cavitated proximal
      caries involved in EDJ, while the therapeutic effects of resin sealant for
      different caries depths still needs to be further confirmed. CLINICAL RELEVANCE:
      Based on existing evidence, dentists should carefully select appropriate micro
      invasive interventions according to the different depths of non-cavitated
      proximal caries.

PMID- 30238418
TI  - Is skip metastases associated with tumor thickness and tumor size in tongue
      carcinoma patients?
AB  - OBJECTIVE: To assess the correlation of skip metastases associated with increase
      in tumor thickness and size of the tumor. MATERIAL AND METHODS: A retrospective
      analysis was carried out from August 2009 to August 2015. In this study, a total
      number of 33 carcinoma tongue patients having T1, T2, and T3 sizes with N0 and N+
      clinical necks who were treated by supraomohyoid neck dissection, extended
      supraomohyoid neck dissection, and modified radical neck dissection were
      analyzed. The data was assessed using Shapiro-Wilk W test, Nagelkerke R2
      regression model, mean, and standard deviation. RESULTS: Metastasis to lymph
      nodes was present in 75% of patients. Level I and level II were the commonest
      sites to be involved, i.e., 20 patients. Three patients had skip metastasis out
      of which two patients had metastasis at level III (6%), and one patient had skip
      metastasis at level IV (3%). CONCLUSION: The incidence of skip metastasis
      increases with tumor thickness and tumor size in tongue carcinoma patients.
      CLINICAL RELEVANCE: The article reveals the positive relationship between tumor
      thickness, tumor size, and skip metastasis. The analysis shows tumor thickness as
      a higher predictor for skip metastasis with odds ratio of 5.5 compared to the
      tumor size having odd ratio 2.

PMID- 30238419
TI  - [Association of circulating tumor cell status with benefit of radiotherapy and
      survival in early-stage breast cancer].

PMID- 30238420
TI  - Effects of Nickel Supplementation on Antioxidant Status, Immune Characteristics,
      and Energy and Lipid Metabolism in Growing Cattle.
AB  - Nickel (Ni) has not been elucidated as an essential mineral in dairy animals,
      though in plants and lower organisms, its role in activation of urease enzyme is
      well known. This study was conducted to evaluate the effect of Ni supplementation
      on intake, growth performance, urease activity, antioxidant and immune status,
      and energy and lipid metabolism in growing cattle. Eighteen growing Hariana
      heifers were randomly allocated into three groups on body weight (125 +/- 3.0 kg)
      and age basis (10 +/- 2.0 months). Feeding regimen was similar in all the groups
      except that treatment groups were supplemented with 0.0 (Ni0.0), 1.5 (Ni1.5), and
      3.0 (Ni3.0) mg of Ni/kg dry matter (DM) in three respective groups. DM intake
      (DMI), average daily gain (ADG), feed efficiency, plasma urease activity,
      biomarkers of antioxidant and immune status, energy and lipid metabolism, and
      plasma Ni levels were observed during the 90-day experimental period. There was
      linear increase (p < 0.05) in mean DMI and ADG without affecting feed efficiency
      was observed in 3.0 mg of Ni/kg DM supplemented heifers. Dietary Ni
      supplementation showed linear increase (p < 0.05) in mean plasma urease activity.
      No effects of (p > 0.05) of Ni supplementation were observed on superoxide
      dismutase (SOD) and catalase (CAT) activity and plasma lipid peroxide (LPO)
      concentration; whereas, mean plasma total antioxidant status (TAS) showed linear
      decrease (p < 0.001) in Ni-supplemented groups. Adding Ni up to 3.0 mg of Ni/kg
      DM did not exert (p > 0.05) any effect on plasma total immunoglobulin and
      immunoglobulin G (IgG) concentrations. Mean plasma cortisol level showed negative
      association with supplemental Ni levels and concentration was found lowest (p <
      0.05) in 3.0 mg of Ni/kg DM-added group. Dietary Ni supplementation did not
      affect mean plasma concentrations of glucose, cholesterol, triglyceride, and non
      esterified fatty acids (NEFA). There was a linear increase (p < 0.001) in plasma
      Ni concentrations as the Ni concentrations increased in the diet. The results of
      present study indicated that dietary supplementation of 3.0 mg of Ni/kg DM
      improved performance of growing cattle by increasing urease activity.

PMID- 30238421
TI  - Evaluation of Some Trace Elements and Vitamins in Major Depressive Disorder
      Patients: a Case-Control Study.
AB  - Major depressive disorder (MDD) is a common mental disorder worldwide; however,
      little is known about its etiology. It is well known that levels of certain trace
      elements are associated with the pathogenesis of some diseases. Accordingly, this
      study aims to evaluate the effect of trace elements and vitamins in the etiology
      of MDD. In this case-control study, sixty men patients with MDD and sixty, age
      and gender matched, control subjects were examined. Serum levels of Cu, Zn, Ni,
      Cr, Mn, Mg, and Al were determined by atomic absorption spectrometry as well as
      serum levels of vitamins E and A were determined using high-performance liquid
      chromatography. The results revealed that there were significantly higher levels
      (p < 0.001) of Cu, Cr, and Al in patients sera compared with control. While there
      were significantly lower levels (p < 0.001) of Zn, Ni, Mn, Mg, vitamin E, and
      vitamin A in MDD patients as compared with control. In addition, high Cu/Zn ratio
      (p < 0.05) was observed with the depressive disorder patients. The present study
      highlights some main indications: a significant relationship between the
      disturbances of element levels and vitamins (E and A) with MDD. Cu and Zn seemed
      to have a crucial role in understanding the pathogenesis of depressive disorders,
      where Cu/Zn ratio could have an important role in the diagnosis and monitoring of
      MDD. Moreover, the results suggest that the reduction in the antioxidant vitamin
      E leads to increased risk of MDD. Finally, more studies on using trace element
      supplementation would be suggested to clarify their effect, in order to improve
      the therapy of MDD.

PMID- 30238422
TI  - The heterologous expression of CmBBX22 delays leaf senescence and improves
      drought tolerance in Arabidopsis.
AB  - KEY MESSAGE: CmBBX22, a transcription factor of chrysanthemum, was verified to
      confer drought tolerance in Arabidopsis thaliana. The BBX proteins are known to
      operate as regulators of plant growth and development, but as yet their
      contribution to the abiotic stress response has not been well defined. Here, the
      chrysanthemum BBX family member CmBBX22, an ortholog of AtBBX22, was found to be
      transcribed throughout the plant, although at varying intensity, and was induced
      by imposing moisture deficiency via exposure to polyethylene glycol. The
      heterologous, constitutive expression of this gene in Arabidopsis thaliana
      compromised germination and seedling growth, but enhanced the plants' ability to
      tolerate drought stress. In transgenic plants challenged with abscisic acid, leaf
      senescence was delayed and the senescence-associated genes and chlorophyll
      catabolic genes SAG29, NYE1, NYE2 and NYC1 were down-regulated. We speculated
      that CmBBX22 may serves as a regulator in mediating drought stress tolerance and
      delaying leaf senescence.

PMID- 30238423
TI  - Beyond the leftward limit of the perceptual span: Parafoveal processing to the
      left of fixation in Chinese reading.
AB  - During reading, Chinese readers have been found to obtain useful visual
      information from one character to the left to three characters to the right of
      fixation. The perceptual span is asymmetrical, and its leftward extent seems to
      be limited compared with the rightward extent. We conducted an experiment to
      investigate whether Chinese readers could process written information beyond the
      leftward extent of the perceptual span. We did this by using a variation of the
      gaze-contingent display change paradigm (Rayner, Cognitive Psychology, 81, 65-81,
      1975) in order to manipulate the parafoveal "postview" that was available to the
      left of where readers were fixating. Each sentence contained an invisible
      boundary. Once the readers' eyes crossed the boundary, all of the characters to
      the left of the boundary except for one, two, or three characters directly to the
      left of the boundary were replaced with visually similar characters. The change
      lasted for only one single fixation, resulting in four different "postview"
      conditions including a control condition (n - 1, n - 2, n - 3, control). The
      results showed that, compared with the control condition, there were more
      regressions to the display change area immediately after readers' eyes crossed
      the boundary in the n - 1, n - 2, and n - 3 conditions, demonstrating that
      readers can acquire information from the three characters to the left of fixation
      at least.

PMID- 30238424
TI  - Seasonal variation and an "outbreak" of frog predation by tamarins.
AB  - We report temporal variation and an "outbreak" of frog predation by moustached
      tamarins, Saguinus mystax, in north-eastern Peruvian Amazonia. Frog predation
      rates were generally very low, but strongly increased in October 2015. Other high
      rates, identified by outlier analyses, were also observed in September-November
      of other years. Over all study years, predation rates in this 3-month period were
      significantly higher than those in the remainder of the year, suggesting a
      seasonal pattern of frog predation by tamarins. Reduced fruit availability or
      increased frog abundance or a combination of both may be responsible for both the
      seasonal pattern and the specific "outbreak" of frog predation.

PMID- 30238425
TI  - Births during 7 years after the translocation of a pair of black-and-gold howler
      monkeys (Alouatta caraya) to a forest fragment in southeast Brazil.
AB  - Fecundity in female primates is influenced by the nutritional condition. If when
      translocated howler monkeys exhibit the same breeding patterns as non
      translocated members of the same genus, it is an indication that the translocated
      monkeys have become well adapted to their release site and that they are likely
      in good nutritional condition. The objective of this study was therefore to
      investigate this pattern by recording copulations (over 5 years) and births (over
      7 years) after the translocation of a pair of black-and-gold howler monkeys
      (Alouatta caraya) and to evaluate their gestation period, seasonality of births,
      and intervals between births. The pair was released in November 2009 on the
      campus of the University of Sao Paulo in Ribeirao Preto, Sao Paulo State, Brazil.
      Data on copulations were collected from January 2010 to March 2011 and from
      January 2012 to December 2014. Births were collected from January 2010 to
      December 2016. During the 5-year observation period, 25 copulations were
      recorded. Seven births were recorded over a period of 7 years, which included
      reproduction of the offspring of the translocated pair. Births occurred in the
      dry season between April and August. The interval between births was
      approximately 1 year. Our data provide insight into the reproduction of howler
      monkeys that have been translocated to a new habitat. Translocation can provide a
      valuable approach for rescuing or restoring Alouatta, whose populations have been
      detrimentally impacted by long-term habitat fragmentation.

PMID- 30238426
TI  - Anthocyanins of Pithecellobium dulce (Roxb.) Benth. Fruit Associated with High
      Antioxidant and alpha-Glucosidase Inhibitory Activities.
AB  - Red arils of Pithecellobium dulce fruit, commonly known as guamuchil, show high
      antioxidant (AOx) and alpha-glucosidase inhibitory (IalphaG) activities, which
      have been mainly associated with the content of unknown anthocyanins. In this
      study, the AOx (i.e., DPPH and ABTS as Trolox equivalents, MUmol TE/g) and
      IalphaG (as half-maximal inhibitory concentration, IC50, mg/mL) activities of the
      anthocyanin-rich fraction (ARF) obtained from red arils were contrasted with
      those of the methanol extract (ME), and the main ARF anthocyanins were
      characterized by HPLC-DAD-ESI-MS, GC-MS and 1H-NMR. The AOx and IalphaG values of
      the ARF (DPPH = 597.8; ABTS = 884.01; IalphaG = 0.06) were better than those of
      the ME (DPPH = 41.5; ABTS = 142.3; IalphaG = 17.5); remarkably, the ARF IalphaG
      value was about 42 times lower than that of acarbose. The main anthocyanins in
      ARF were pelargonidin 3-O-glucoside and cyanidin 3-O-glucoside. Thus, the
      consumption of red P. dulce arils could provide health benefits for
      prevention/treatment of chronic degenerative diseases such as diabetes.

PMID- 30238427
TI  - PAXX Participates in Base Excision Repair via Interacting with Pol beta and
      Contributes to TMZ Resistance in Glioma Cells.
AB  - Non-homologous end joining (NHEJ) is one of the major DNA repair pathway in
      mammalian cell that can ligate a variety of DNA ends. However, how does all NHEJ
      factors communicate and organize together to achieve the final repair is still
      not clear. PAralog of XRCC4 and XLF (PAXX) was a new factor identified recently
      that play an important role in NHEJ. PAXX contributes to efficient NHEJ by
      interacting with Ku, which is a NHEJ key factor, and PAXX deficiency cause
      sensitivity to DNA double-strand break repair (DSBR). We observed that PAXX
      deficient cells showed slight increase of homologous recombination (HR, which is
      another major DSBR repair pathways in mammalian cells). More importantly, we
      found that PAXX contributes to base excision repair pathway via interaction of
      polymerase beta (pol beta). Temozolomide (TMZ) is one of the standard
      chemotherapies widely applied in glioblastoma. However, TMZ resistance and lack
      of potent chemotherapy agents can substitute TMZ. We observed that PAXX
      deficiency cause more sensitivity to TMZ-resistant glioma cells. In conclusion,
      the PAXX contributes to a variety of DNA repair pathways and TMZ resistance.
      Therefore, inhibition of PAXX may provide a promising way to overcome TMZ
      resistance and improve TMZ therapeutic effects in glioma treatment.

PMID- 30238429
TI  - Effect of CBX7 deficiency on the socket healing after tooth extractions.
AB  - CBX7 is shown to down-regulate the expression of osteopontin (OPN) that is
      associated with osteoblast function. Here, we studied the role of CBX7 in the
      wound healing of tooth extraction socket in which osteoblast activity is critical
      via comparison between CBX7-knockout (CBX7-/-) mice and their wild-type (WT)
      counterparts of 6 weeks old with maxillary first molar extracted. Mice were
      euthanized at 7, 14, and 21 days after extractions, and alveolar sockets were
      assessed by semi-quantitative histomorphometry for hard tissue healing, including
      new bone fill (Masson's trichrome staining), osteoblast activity (OPN/osterix,
      Osx), osteoclast activity (tartrate-resistant acid phosphatase, TRAP), and for
      soft tissue healing, including blood vessels (alpha smooth muscle actin, alpha
      SMA). Also, the bone microarchitecture was evaluated by micro-CT. In radiological
      analysis, CBX7-/- mice increased bone mass significantly more than WT mice did.
      Consistently, both the amount of new bone fill and OPN/Osx-immunopositive cells
      in the extraction sockets were significantly increased in CBX7-/- mice at each
      time point with respect to their WT siblings, while osteoclast number exhibited a
      trend of more increase in CBX7-/- mice at all time points as well. In agreement
      with enhanced bone formation during socket healing, significantly elevated alpha
      SMA-immunopositive area was noted in CBX7-/- mice in contrast to WT mice. Taken
      together, these data suggest that CBX7 deficiency has a positive effect on tooth
      extraction socket healing.

PMID- 30238428
TI  - Assessment of patient-reported outcomes (PROs): treatment satisfaction,
      medication adherence, and quality of life (QoL) and the associated factors in
      postmenopausal osteoporosis (PMO) patients in Korea.
AB  - Patient-reported outcomes (PROs) provide practical guides for treatment; however,
      studies that have evaluated PROs of women in Korea with postmenopausal
      osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide
      hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs
      related to treatment satisfaction, medication adherence, and quality of life
      (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment.
      Patient demographics, clinical characteristics, treatment patterns, PROs, and
      experience using medication were collected. The 14-item Treatment Satisfaction
      Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness,
      side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky
      Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions
      questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale
      score range, 0-100) were used. To investigate factors associated with PROs,
      linear (treatment satisfaction/QoL) or logistic (medication adherence) regression
      analyses were conducted. A total of 1804 patients (age, 62 years) were
      investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly
      medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily
      selective estrogen receptor modulator. Several patients reported gastrointestinal
      (GI) events (31.6%) and dental visits due to problems (24.1%) while using
      medication. Factors associated with the highest OS-MMAS domain scores were
      convenience and global satisfaction. GI events were associated with non
      adherence. TSQM scores for effectiveness, side effects, and GI risk factors were
      significantly associated with QoL. Our study elaborately assessed the factors
      associated with PROs of Korean PMO women. Based on our findings, appropriate
      treatment-related adjustments such as frequency/choice of medications and GI risk
      management may improve PROs.

PMID- 30238430
TI  - Change of skeletal muscle mass in patients with pheochromocytoma.
AB  - The effects of catecholamine excess due to pheochromocytoma on body composition,
      including skeletal muscle mass, are unknown. Here, we investigated the effects of
      catecholamine metabolites on body composition in subjects with pheochromocytoma.
      After body compositions using bioelectrical impedance analysis, urinary
      metanephrine (UM), and urinary normetanephrine (UNM) were measured in 16 patients
      with pheochromocytoma and 224 patients with nonfunctioning adrenal incidentaloma
      (NFAI), we compared skeletal muscle mass and fat mass (FM) between the two
      groups. After adjustments for confounders, UM (beta = - 0.171, P = 0.006) and UNM
      (beta = - 0.249, P < 0.001) levels were correlated inversely with skeletal muscle
      mass index (SMI), but not FM or percentage FM (pFM), in all subjects. Patients
      with pheochromocytoma had lower ASM by 7.7% (P = 0.022) and SMI by 6.6% (P =
      0.001) than patients with NFAI. Conversely, FM and pFM were not statistically
      different between the two groups. The odds ratio for low skeletal muscle mass in
      the presence of pheochromocytoma was 10.33 (95% confidence interval, 2.65-40.22).
      Our results indicate that patients with pheochromocytoma have a reduced skeletal
      muscle mass and suggest that catecholamine excess has adverse effects on skeletal
      muscle metabolism.

PMID- 30238431
TI  - Overweight and underweight are risk factors for vertebral fractures in patients
      with type 2 diabetes mellitus.
AB  - The aim of this cross-sectional study was to examine the association between body
      mass index (BMI) and the prevalence of vertebral fracture (VF) in Japanese
      patients with type 2 diabetes (T2DM). A total of 798 patients with T2DM were
      enrolled. VF was determined semi-quantitatively using lateral X-ray films. The
      association between BMI quartiles (Q1: <= 21.2 kg/m2, Q2: 21.3-23.4 kg/m2, Q3:
      23.5-25.8 kg/m2, Q4: 25.9<= kg/m2) and the presence of VF was examined. Multiple
      logistic regression analyses adjusted for age, sex, diabetes duration, hemoglobin
      A1c (HbA1c), estimated glomerular filtration rate, and albumin showed that Q1,
      Q3, and Q4 were significantly associated with an increased VF risk compared to
      Q2, which served as a reference [Q1; odds ratio (OR) = 1.91, 95% confidence
      interval (CI) 1.24-2.95, p = 0.004, Q3; OR = 1.65, 95% CI 1.07-2.55, p = 0.023,
      and Q4; OR = 2.18, 95% CI 1.39-3.41, p < 0.001]. Moreover, these associations
      remained significant after additional adjustment for femoral neck T-score, a bone
      resorption marker, urinary N-terminal cross-linked telopeptide of type-I
      collagen, and use of insulin and thiazolidinedione. Our study shows for the first
      time that both overweight and underweight were associated with the bone mineral
      density (BMD)-independent risk of VF in patients with T2DM. Therefore, body
      weight control should be considered as a protective measure against diabetes
      related bone fragility.

PMID- 30238432
TI  - Congenital hypophosphataemia in adults: determinants of bone turnover markers and
      amelioration of renal phosphate wasting following total parathyroidectomy.
AB  - Congenital hypophosphataemia (CH) is a collection of disorders that cause
      defective bone mineralisation manifesting with rickets in childhood and
      osteomalacia in adulthood. Bone turnover markers (BTMs) are surrogate measures of
      metabolic bone disease severity. We explored the utility of BTMs in 27 adults
      with CH: 23 had X-linked hypophosphataemia (XLH), of whom 2 were hypoparathyroid
      post-total parathyroidectomy (PTx); 2 had autosomal dominant hypophosphataemic
      rickets (ADHR), and 2 had none of the known mutations. We measured the renal
      tubular maximum reabsorption rate of phosphate (TmP/GFR), C-terminal fibroblast
      growth factor 23 (FGF23), parathyroid hormone (PTH), ionised calcium, 1,25
      dihydroxyvitamin D [1,25(OH)2D], and a panel of BTMs: serum bone-specific
      alkaline phosphatase (bone ALP), osteocalcin (Oc), total procollagen type I amino
      terminal propeptide (PINP), and carboxy-terminal telopeptide of type I collagen
      (CTX); and urine amino-terminal telopeptides of type I collagen (uNTX). After
      excluding 2 patients with XLH and PTx, the frequency of abnormal elevation in
      BTMs was: bone ALP (96%); CTX (72%); PINP (52%); uNTX (48%); Oc (28%). The
      strongest association with bone ALP was TmP/GFR. Those patients receiving
      phosphate supplements and alfacalcidol had significant elevation in CTX. The 2
      patients with XLH and PTx had normalisation of TmP/GFR and near normalisation of
      BTMs post-operatively, despite marked elevation in both C-terminal and intact
      FGF23. In conclusion, BTMs in our CH patients indicated that most have
      abnormalities consistent with osteomalacia and many have mild secondary
      hyperparathyroidism; and the normalisation of TmP/GFR after total PTx in 2 cases
      of XLH remains unexplained, but possible causes are speculated.

PMID- 30238433
TI  - Riociguat for the Treatment of Raynaud's Phenomenon: A Single-Dose, Double-Blind,
      Randomized, Placebo-Controlled Cross-Over Pilot Study (DIGIT).
AB  - BACKGROUND AND OBJECTIVE: Raynaud's phenomenon (RP) is characterized by transient
      digital ischemia and is commonly associated with connective tissue disease.
      Treatment remains unsatisfactory. Here we evaluate the efficacy, safety, and
      pharmacokinetics of a single dose of the soluble guanylate cyclase stimulator
      riociguat in RP. METHODS: DIGIT was a double-blind, randomized, placebo
      controlled pilot study. Patients with primary or secondary RP were randomized to
      a single oral dose of riociguat 2 mg or placebo in a cross-over design (7 +/- 3
      days). Efficacy was assessed as placebo-corrected change in digital blood flow 2
      h post-dose at room temperature (RT) or following cold exposure (CE), measured by
      laser-speckle contrast analysis. Patients were regarded as responders if placebo
      corrected digital blood flow increased by >= 10% from baseline at RT or after CE.
      RESULTS: Of 20 eligible patients, 17 (85%) were female and mean [standard
      deviation (SD)] age was 52 (13.8) years. Placebo-corrected changes in digital
      blood flow were + 46% [90% confidence interval (CI) - 6 to + 98] at RT and - 9%
      (90% CI - 63 to + 44) after CE, with high inter-individual variability. Eight
      patients (40%) were responders at RT, and 12 (60%) after CE. Riociguat increased
      mean (SD) digital blood flow in responders at RT by + 136% (114) and in
      responders following CE by + 39% (53). Riociguat was well tolerated, with few
      adverse events. CONCLUSION: In this pilot study, single-dose riociguat was well
      tolerated in patients with RP and resulted in improved digital blood flow in some
      patient subsets, with high inter-individual variability. Long-term evaluation is
      warranted.

PMID- 30238435
TI  - Writer's cramp: a new dystonic feature in spinocerebellar ataxia type 3.

PMID- 30238434
TI  - Clinically Relevant Prognostic Parameters in Differentiated Thyroid Carcinoma.
AB  - Although differentiated thyroid carcinomas typically pursue an indolent clinical
      course, it is important to identify the subset of tumors that are most likely to
      behave aggressively so that patients with these tumors are counseled and treated
      appropriately. Extent of disease is fundamental to the prognostication for
      differentiated thyroid carcinoma; however, there are additional histologic
      features of the tumor separate from extent of disease that have been shown to
      affect clinical course. This review will start with a discussion of aggressive
      variants of papillary thyroid carcinoma, move to the prognostic significance of
      vascular invasion in follicular thyroid carcinoma, and finish with a discussion
      of Hurthle cell carcinoma, with an emphasis on why it is not considered a subtype
      of follicular thyroid carcinoma in the 2017 WHO Classification of Tumors of
      Endocrine Organs.

PMID- 30238436
TI  - The contribution of sexual selection to ecological and mutation-order speciation.
AB  - Abundant evidence supports a role for sexual selection in the evolution of
      reproductive isolation, and it is thus unsurprising that much attention has been
      given, both conceptually and empirically, to understanding its role in
      speciation. In doing so, debate has arisen on how sexual selection fits within
      the much used ecological versus mutation-order classification of speciation
      mechanisms, with sexual selection often presented as a distinct third
      alternative. We argue that models of speciation by sexual selection include a
      fundamental role of divergent selection between environments or mutation order in
      initiating the process. Rather than representing a unique mechanism, sexual
      selection layers a coevolutionary process between males and females on top of the
      classic mechanisms such that the evolution of each sex can now be driven by
      divergent selection, mutation order, and selection arising from interactions with
      the other sex. In addition to blurring the distinction between ecological and
      mutation-order speciation, this coevolutionary process is likely to speed
      divergence. Sexual selection is not unique in this way; coevolutionary processes
      can similarly arise from ecological interactions between populations or species,
      with similar results. Ultimately, understanding the contribution of sexual
      selection to speciation will require identifying the processes that drive the
      divergence of mating biases.

PMID- 30238437
TI  - Risk factors of acute kidney injury in children after cardiac surgery-Reply.

PMID- 30238439
TI  - Pseudodidymosis: nevus psiloliparus with aplasia cutis congenita, an initial
      manifestation of Haberland syndrome.

PMID- 30238438
TI  - INTEND II randomized clinical trial of intraoperative duct endoscopy in
      pathological nipple discharge.
AB  - BACKGROUND: The majority of lesions resulting in pathological nipple discharge
      are benign. Conventional surgery is undirected and targeting the causative lesion
      by duct endoscopy may enable more accurate surgery with fewer complications.
      METHODS: Patients requiring microdochectomy and/or major duct excision were
      randomized to duct endoscopy or no duct endoscopy before surgery. Primary
      endpoints were successful visualization of the pathological lesion in patients
      randomized to duct endoscopy, and a comparison of the causative pathology between
      the two groups. The secondary endpoint was to compare the specimen size between
      groups. RESULTS: A total of 68 breasts were studied in 66 patients; there were 31
      breasts in the duct endoscopy group and 37 in the no-endoscopy group. Median age
      was 49 (range 19-81) years. Follow-up was 5.4 (i.q.r. 3.3-8.9) years in the duct
      endoscopy group and 5.7 (3.1-9.0) years in no-endoscopy group. Duct endoscopy had
      a sensitivity of 80 (95 per cent c.i. 52 to 96) per cent, specificity of 71 (44
      to 90) per cent, positive predictive value of 71 (44 to 90) per cent and negative
      predictive value of 80 (52 to 96) per cent in identifying any lesion. There was
      no difference in causative pathology between the groups. Median volume of the
      surgical resection specimen did not differ between groups. CONCLUSION: Diagnostic
      duct endoscopy is useful for identifying causative lesions of nipple discharge.
      Duct endoscopy did not influence the pathological yield of benign or malignant
      diagnoses nor surgical resection volumes. Registered as INTEND II in CancerHelp
      UK clinical trials database (https://www.cancerresearchuk.org/about-cancer/find-a
      clinical-trial/a-study-looking-at-changes-inside-the-breast-ducts-of-women-who
      have-nipple-discharge).

PMID- 30238440
TI  - Gardner-Diamond syndrome: a systematic review of treatment options for a rare
      psychodermatological disorder.
AB  - Gardner-Diamond syndrome (GDS) is a rare psychodermatological condition
      characterized by the formation of spontaneous, painful skin lesions that develop
      into ecchymosis following episodes of severe physiological or psychological
      stress. The majority of GDS cases occur in young adult females, and although the
      etiology of this rare disorder is unknown, there appears to be a psychological
      component correlated with the coexistence of previous psychiatric diagnoses. Due
      to the rare nature of this disorder, there exist few guidelines for prompt
      clinical diagnosis and optimal treatment. Here, a systematic review was conducted
      to include 45 cases of patients with GDS to better understand clinical
      presentation as well as current treatment options. Ultimately, GDS is a diagnosis
      of exclusion after other coagulopathies and causes of purpura are ruled out. High
      clinical suspicion following laboratory and clinical exclusion of known
      physiological causes is necessary for diagnosis. Selective serotonin reuptake
      inhibitors (SSRIs) and corticosteroids are cost effective first line treatments
      for GDS with proven efficacy in symptomatic relief. GDS refractory to initial
      treatment may require regular psychotherapy and titrated SSRI dosages to achieve
      long-term success. This review of available case studies serves to
      comprehensively describe the clinical presentation and available treatment
      approaches to this rare psychodermatological disorder.

PMID- 30238441
TI  - Further examination of video-based preference assessments without contingent
      access.
AB  - The first purpose of this study was to attempt to replicate previous findings
      that video-based preference assessments without access to selected stimuli may
      accurately predict relative reinforcing efficacy of stimuli. To do this, we
      conducted a concurrent operant reinforcer assessment in which we evaluated the
      relative reinforcing value of highly preferred and less preferred items
      identified in a video-based preference assessment. The second purpose of this
      study was to begin to evaluate the potential behavioral mechanisms responsible
      for the validity of this assessment. To conduct this analysis, we evaluated the
      relative reinforcing value of those same stimuli depicted in video format and
      then compared results to results obtained during the reinforcer assessment for
      tangible stimuli. For all five participants, stimuli identified as highly
      preferred functioned as reinforcers, and four of five participants, responding
      during the reinforcer assessment was similar in the presence of tangible stimuli
      and videos depicting those stimuli.

PMID- 30238442
TI  - Parent-Infant Room Sharing During the First Months of Life: Longitudinal Links
      With Behavior During Middle Childhood.
AB  - Current recommendations encourage parent-infant room sharing for the first 6
      months of life. This longitudinal study (N = 193) is the first to examine long
      term relations of early room sharing with three domains of child behavior: sleep,
      behavior problems, and prosocial behavior. Information on room sharing was
      collected daily for infants' first 6 months. At ages 6, 7, and 8 years, outcomes
      were assessed with maternal and teacher questionnaires and behavioral
      observations. Early room sharing was not related to sleep problems or behavior
      problems. Additionally, more weeks of room sharing were positively related to
      higher maternal ratings of child sleep quality and more prosocial behavior. In
      conclusion, early room sharing appears to be related to positive, but not
      negative, behavior outcomes in middle childhood.

PMID- 30238443
TI  - Human body symmetry and immune efficacy in healthy adults.
AB  - OBJECTIVES: More symmetric organisms are perceived as more attractive.
      Fluctuating asymmetry (FA) i.e. small, random deviations from perfect bilateral
      symmetry, is supposed to inform about developmental instability. According to the
      good genes hypothesis, a low level of FA is a putative cue to an organism's
      biological quality. An important aspect of this quality is the immune system
      functioning. The aim of this study was to evaluate the relationship between
      immune system functioning and body symmetry in healthy people. MATERIALS AND
      METHODS: The composite body FA (cFA) was assessed on the basis of six bilateral
      traits (on hands and feet). The ISF was determined by many innate (total
      complement and lysozyme activity, neutrophils function) and adaptive immune
      parameters (T CD3 and B CD19 lymphocytes, total IgA and IgG and response to flu
      vaccine). A total of 98 men and 92 women were subjected to flu (among them 37 men
      and 30 women also to tetanus) vaccination. The blood samples were collected
      before and 4 weeks after the antigens exposure. Immunomodulatory factors:
      participant's age, body fat, and free testosterone level, were controlled.
      RESULTS: Apart from the weak positive association between CD3 or CD19 and cFA in
      men, we found no association between the level of body symmetry and the rest of
      the analyzed immune parameters for both sexes. DISCUSSION: Our results are the
      opposite of the good genes hypothesis prediction and suggest that in western,
      healthy populations, human mate preferences for more symmetric bodies are not
      related to immune competence.

PMID- 30238444
TI  - A Randomized Trial of Early Endovenous Ablation in Venous Ulceration: a critical
      appraisal.
AB  - : Manjit S. Gohel et al. (N Engl J Med 2018; 378: 2105-2114) aimed to compare
      early endovenous ablation vs. deferred endovenous ablation of superficial venous
      reflux regarding time to healing of venous leg ulcers, rate of healing at 24
      weeks, recurrence rate, ulcer-free time, and health-related quality of life.
      SETTING AND DESIGN: This multicentre, parallel-group (ratio 1:1), randomized
      controlled trial was conducted in a vascular surgery department setting at 20
      participating centres across the United Kingdom. STUDY EXPOSURE: 450 patients
      with venous leg ulcers were randomly assigned to receive compression therapy and
      undergo early endovenous ablation of superficial venous reflux within 2 weeks
      after randomization (early-intervention group) or to receive compression therapy
      alone, with consideration of endovenous ablation deferred until after the ulcer
      was healed or until 6 months after randomization if the ulcer was unhealed
      (deferred-intervention group). OUTCOMES: The primary outcome was the time to
      ulcer healing. Secondary outcomes were the rate of ulcer healing at 24 weeks, the
      rate of ulcer recurrence, the length of time free from ulcers (ulcer-free time)
      during the first year after randomization, and patient-reported health-related
      quality of life. TRIAL INTERVENTIONS: Endovenous laser or radiofrequency
      ablation, ultrasound-guided foam sclerotherapy, or non-thermal, nontumescent
      methods of treatment (such as cyanoacrylate glue or mechanochemical ablation)
      were performed either alone or in combination. The treating clinical team
      determined the method and strategy of endovenous treatment. RESULTS: The time to
      ulcer healing was shorter in the early-intervention group than in the deferred
      intervention group. Furthermore, more patients had healed ulcers with early
      intervention (hazard ratio for ulcer healing, 1.38; 95% confidence interval CI,
      1.13 to 1.68; p=0.001). The median time to ulcer healing was 56 days (95% CI, 49
      to 66) in the early-intervention group and 82 days (95% CI, 69 to 92) in the
      deferred-intervention group. The rate of ulcer healing at 24 weeks was 85.6% in
      the early-intervention group and 76.3% in the deferred-intervention group. The
      median ulcer-free time during the first year after trial enrolment was 306 days
      (interquartile range 240 to 328) in the early-intervention group and 278 days
      (interquartile range, 175 to 324) in the deferred-intervention group (P=0.002).
      The most common complications were pain and deep-vein thrombosis (early
      intervention: pain 6/28, DVT 9/28, deferred-intervention: pain 6/24, DVT 3/24).
      CONCLUSIONS: Gohel et al. conclude that early endovenous ablation of superficial
      venous reflux results in faster healing of venous leg ulcers than deferred
      endovenous ablation. Patients assigned to the early-intervention group also had
      longer ulcer-free time during the first year after randomization. This article is
      protected by copyright. All rights reserved.

PMID- 30238445
TI  - The effects of general anaesthesia on oxygen consumption: A meta-analysis guiding
      future studies on perioperative oxygen transport.
AB  - BACKGROUND: Increased oxygen extraction, the ratio of consumption to delivery,
      has been associated with poor outcome after surgery. Oxygen consumption (VO2) can
      change in several ways in the perioperative period, but is seldom monitored
      directly in routine care. This study investigates the effects of general
      anaesthesia on VO2. METHODS: We searched PubMed, EMBASE, and Cochrane Library
      1946-2018 for studies including VO2 measurements before and after anaesthesia
      induction. Quality was assessed by Cochrane risk of bias tool and NIH Quality
      Assessment tool for before-and-after studies. Changes in VO2 after anaesthesia
      induction were pooled in a random effects model meta-analysis with standardized
      mean differences transformed to absolute changes of VO2. Changes in VO2 after
      surgical incision and after recovery from anaesthesia were analysed as secondary
      outcomes in the included studies. RESULTS: Twenty-four studies including 453
      patients were analysed for VO2 changes induced by anaesthesia. Studies were
      published during 1969-2000 and mean age of patients ranged 28-70 years. VO2
      decreased after anaesthesia induction by -65 (-75; -55, 95% CI) mL min-1 and
      indexed VO2 (VO2I) by -33 (-38; -28, 95% CI) mL min-1  m-2 . After surgical
      incision and in the post-operative period VO2 increased again. Heterogeneity was
      considerable among the studies and the overall quality of evidence was very low.
      CONCLUSIONS: General anaesthesia probably reduces oxygen consumption but the
      effect estimate is uncertain. Given the limited generalizability and low quality
      of the available evidence, new studies in modern perioperative settings and in
      today's older high-risk surgical patient populations are needed.

PMID- 30238446
TI  - Similar evolution of pain symptoms and quality of life in women with and without
      endometriosis undergoing assisted reproductive technology (ART).
AB  - INTRODUCTION: Altogether 10% of all women of fertile age suffer from
      endometriosis, and up to 25% of these women require assisted reproductive
      technology (ART) to conceive. During ART the process of controlled ovarian
      stimulation causes high levels of estrogen, which in theory increases the risk of
      the progression of symptoms related to this estrogen-dependent disorder. Because
      several case reports have described the worsening of endometriosis during ART we
      carried out this study to investigate whether controlled ovarian stimulation
      during ART aggravates symptoms in women with endometriosis in terms of pain and
      quality of life. MATERIAL AND METHODS: This prospective cohort study was based on
      questionnaires containing the Endometriosis Health Profile (EHP-30) and pain
      evaluated on the numerical rating scale (NRS). Women aged below 40 years were
      recruited and divided into three groups according to their endometriosis and ART
      status. Questionnaires were administered before and after controlled ovarian
      stimulation in one ART cycle. Change in EHP-30 and NRS scores from the 1st to 2nd
      questionnaire was analyzed. RESULTS: In total 52 women with endometriosis
      undergoing ART, 50 not undergoing ART, and 52 without endometriosis undergoing
      ART completed two questionnaires each. Both groups with endometriosis experienced
      a small increase in their quality of life, while women without endometriosis
      experienced a decrease. Pelvic pain worsened among women undergoing ART, but no
      greater worsening was detected among women with endometriosis compared with women
      without. CONCLUSIONS: This study showed no worsening in quality of life and a
      slight worsening in pelvic pain during ART regardless of endometriosis status.

PMID- 30238447
TI  - Design and synthesis of BRC analogous peptides and their interactions with a key
      p53 peptide.
AB  - Mutations in breast cancer susceptibility gene 2 (BRCA2) can lead to chromosomal
      instability and result in breast cancer, which is strongly associated with p53
      mutations. Here, based on the crystal structure of BRC4 and p53, the spatial
      structure of BRC2 and p53 (171-192) was simulated, providing structural basis for
      the site-specific mutation of BRC2. The BRC analogous peptides and p53 (171-192)
      were synthesized, and the interaction between the mutant peptide and p53 (171
      192) was studied using circular diachronic spectroscopy and fluorescence
      spectroscopy. The results show that the mutations of amino acid residues
      constituting the BRC2 alpha-helix significantly affect the structure and
      interaction of BRC analogs and p53 (171-192), which provides support for
      understanding the structure of the BRC repeat motifs and its interaction pattern
      with p53.

PMID- 30238448
TI  - Long-term efficacy follow-up of tension-free vaginal tape obturator in patients
      with stress urinary incontinence with or without cystocele.
AB  - OBJECTIVE: To assess the long-term outcomes of tension-free vaginal tape
      obturator (inside-out) (TVTO) with or without anterior colporrhaphy. METHODS: The
      present prospective follow-up observational study included patients attending the
      2nd Department of Obstetrics and Gynecology, Aretaieio Hospital, University of
      Athens, Greece, between April 3 and December 20, 2017, for follow-up care after
      treatment for urodynamic stress urinary incontinence (USUI) with or without
      cystocele. Patients without cystocele had been treated with TVTO only; those with
      cystocele underwent TVTO with anterior colporrhaphy. The primary outcome was the
      objective cure rate assessed by the cough stress test during filling cystometry.
      RESULTS: Follow-up data were available for 70 patients who underwent TVTO only
      and 38 who underwent TVTO and anterior colporrhaphy. The mean follow-up period
      was 13 years. Objective cure was achieved for 57 (81%) patients in the TVTO-only
      group and 32 (84%) patients in the TVTO and anterior colporrhaphy group.
      Regarding cystocele management, objective cure was recorded for 35 (92%)
      patients. CONCLUSION: At 13-year follow-up, anterior colporrhaphy demonstrated a
      cure rate of 92% in the management of cystocele, and 84% in the management of
      cystocele and USUI when combined with TVTO. TVTO alone for the management of USUI
      had an objective cure rate of 81%.

PMID- 30238449
TI  - Risk factors of acute kidney injury after pediatric cardiac surgery.

PMID- 30238450
TI  - Adult attachment as a predictor and moderator of psychotherapy outcome: A meta
      analysis.
AB  - Bowlby's attachment theory describes characteristic patterns of relating to close
      others and has important implications for psychotherapy. Attachment patterns have
      been characterized as secure (healthy interdependence with others), anxious
      (overdependence on others), and avoidant (difficulty relying on others). We
      update a previous meta-analysis to determine the association of patient
      attachment with psychotherapy outcome. Meta-analysis of 36 studies (3,158
      patients) suggested that patients with secure attachment pretreatment show better
      psychotherapy outcome than insecurely attached patients. Further, improvements in
      attachment security during therapy may coincide with better treatment outcome.
      Finally, preliminary moderator analyses suggest that those who experience low
      pretreatment attachment security may find better treatment outcome in therapy
      that incorporates a focus on interpersonal interactions and close relationships.
      The article closes with research limitations, diversity considerations, and
      therapeutic practices.

PMID- 30238452
TI  - An evaluation of a punisher assessment for decreasing automatically reinforced
      problem behavior.
AB  - We extended research on the identification and evaluation of potential punishers
      for decreasing automatically reinforced problem behavior in four individuals with
      autism spectrum disorder. A punisher selection interview was conducted with lead
      clinicians to identify socially acceptable punishers. During the treatment
      evaluation, treatment phases were introduced sequentially and included
      noncontingent reinforcement (NCR), NCR and differential reinforcement of
      alternative behavior (DRA), and NCR-and-DRA with punishment. During the NCR-and
      DRA with punishment phase, four to five potential punishers were evaluated using
      a multielement design. Dependent measures included the target problem behavior,
      appropriate item engagement, and emotional responding. For all participants, NCR
      and-DRA was not effective and punishment was necessary. However, the most
      effective punisher identified in the context of NCR-and-DRA differed across
      participants.

PMID- 30238451
TI  - AtROP6 is involved in reactive oxygen species signaling in response to iron
      deficiency stress in Arabidopsis thaliana.
AB  - Understanding the mechanism of iron (Fe)-deficiency responses is crucial for
      improving plant Fe bioavailability. Here, we found that the Arabidopsis Rho-like
      GTPase 6 mutant (rop6) is less sensitive to Fe-deficiency responses and has
      reduced levels of reactive oxygen species (ROS) compared to wild-type (WT), while
      AtROP6-overexpressing seedlings exhibit more sensitivity to Fe-deficiency
      responses and has higher levels of ROS compared to WT. Moreover, treatment with
      H2 O2 improves the sensitivity to Fe-deficiency responses in rop6 mutants. By
      using the yeast two-hybrid system, we further demonstrate the direct interaction
      between AtROP6 and Arabidopsis respiratory burst oxidase homolog D (AtRBOHD),
      which controls the generation of ROS. Overall, we suggest that AtROP6 is involved
      in AtRBOHD-mediated ROS signaling to modulate Fe-deficiency responses in
      Arabidopsis thaliana.

PMID- 30238453
TI  - Attending to gender in psychotherapy: Understanding and incorporating systems of
      power.
AB  - This study reviews the research evidence on the effectiveness of attending to
      clients' gender identity and gender as a system of power in psychotherapy. We
      begin with definitions and measures of gender identity and provide clinical
      examples. Next, we summarize our search for studies to conduct two meta-analyses
      on: (a) randomized controlled trials (RCTs) of psychotherapy conducted with
      transgender clients, and (b) RCTs of the outcomes of psychotherapies that attend
      explicitly to gender as a system of power compared with another bona-fide
      psychotherapy. Our search did not yield studies that fit either search criteria;
      thus, meta-analyses were not conducted. Instead, we conducted a content analysis
      of the 10 qualitative and quantitative studies on psychotherapy with transgender
      individuals. We conclude by highlighting the limitations of the research base,
      describing diversity considerations, and recommending therapeutic practices that
      attend to gender, gendered systems of power, oppression, and privilege.

PMID- 30238454
TI  - Radiotherapy-induced Pemphigus Foliaceous: a rare adverse effect of breast cancer
      therapy.

PMID- 30238455
TI  - Engaging in LGBQ+ affirmative psychotherapies with all clients: Defining themes
      and practices.
AB  - The clinical need for lesbian, gay, bisexual, and queer (LGBQ+) affirmative
      psychotherapies has been widely recognized; however, empirical research on the
      outcomes of such psychotherapies is limited. Moreover, key questions about whom
      such psychotherapies are for and what they comprise require critical
      consideration. We begin by offering definitions to answer these questions and
      delineate four key themes of LGBQ+ affirmative psychotherapies. We conceptualize
      LGBQ+ affirmative psychotherapies not as sexual orientation group-specific, but
      rather as considerations and practices that can be applied with all clients. We
      then summarize our own search for studies to attempt a meta-analysis and we
      discuss limitations and directions for research based on our literature review.
      We end by delineating diversity considerations and recommending therapeutic
      practices for advancing LGBQ+ affirmative psychotherapy with clients of all
      sexual orientations.

PMID- 30238456
TI  - Using microwave cooking to evaluate tenderness and its relationship to sensory
      analysis.
AB  - This study evaluated a microwave (Mw) cooking method for determining beef
      toughness using the Warner-Bratzler slice shear force (WBsSF) protocol.
      Longissimus thoracis muscles were aged for 1, 10, 19, and 28 days at 4C. They
      were then either cooked on a clam-shell grill until reaching an internal
      temperature of 72C, in a Mw for 100 s at maximum power (Mw100) or for 140 s at
      60% of maximum power (Mw60). Cooking loss and shear force (SF) values were higher
      in Mw samples than in grilled ones. SF assessment by grill and Mw100 were able to
      discriminate tenderness by aging times in the same way as the sensory panel. The
      SF measured in a grilled sample had higher repeatability (R = .74) and
      correlation with sensory scores (r = -.79) than Mw100 (R = .61; r = -.62) and
      Mw60 (R = .51; r = -.53). Mw100 can be considered as an appropriate alternative
      for the WBsSF protocol. PRACTICAL APPLICATIONS: Tenderness is the most important
      attribute for consumers. Many studies have evaluated tenderness in meat and
      different protocols for cooking. This work was intended to optimize and evaluate
      the use of the microwave as a cooking method for shear force determination,
      against a standard protocol and establish the correlation to sensory tenderness.

PMID- 30238457
TI  - Factors affecting the Affordable Care Act Marketplace stand-alone pediatric
      dental plan premiums.
AB  - BACKGROUND: Children from lower income families have inadequate dental insurance
      coverage and poorer dental health in the United States. The Affordable Care Act
      (ACA) created Health Insurance Exchange Marketplaces to increase competition
      among health insurers and to provide low-income families with less costly health
      plans. The study examined Marketplace pediatric stand-alone dental plans (SADPs)
      and factors that affect their premiums. METHODS: The data used were 2016 Federal
      Facilitated and State-Partnership Marketplace pediatric SADP data. Ordinary least
      squares regressions were applied to estimate contributing factors' effects on
      SADP premiums. RESULTS: Great premium variation was found among low and high
      coverage level SADPs, respectively. Premiums of Health Maintenance Organization
      (HMO) SADPs were significantly less expensive than Preferred Provider
      Organization (PPO) SADPs. SADPs charged significantly higher premiums for more
      types of services covered. SADPs also charged higher premiums in states where
      there are larger proportions of low-income people who report poor dental health,
      more dentists per capita, or higher dentists' wages. The number of insurance
      companies offering pediatric SADPs in a Marketplace was negatively associated
      with premiums. CONCLUSION: The current Marketplace pediatric SADPs may have
      limited effects on increasing economically disadvantaged children's access to
      quality dental care. Marketplaces can promote competition among its pediatric
      dental insurers on providing lower-cost pediatric SADPs.

PMID- 30238458
TI  - Logging and soil nutrients independently explain plant trait expression in
      tropical forests.
AB  - Plant functional traits regulate ecosystem functions but little is known about
      how co-occurring gradients of land use and edaphic conditions influence their
      expression. We test how gradients of logging disturbance and soil properties
      relate to community-weighted mean traits in logged and old-growth tropical
      forests in Borneo. We studied 32 physical, chemical and physiological traits from
      284 tree species in eight 1 ha plots and measured long-term soil nutrient
      supplies and plant-available nutrients. Logged plots had greater values for
      traits that drive carbon capture and growth, whilst old-growth forests had
      greater values for structural and persistence traits. Although disturbance was
      the primary driver of trait expression, soil nutrients explained a statistically
      independent axis of variation linked to leaf size and nutrient concentration.
      Soil characteristics influenced trait expression via nutrient availability,
      nutrient pools, and pH. Our finding, that traits have dissimilar responses to
      land use and soil resource availability, provides robust evidence for the need to
      consider the abiotic context of logging when predicting plant functional
      diversity across human-modified tropical forests. The detection of two
      independent axes was facilitated by the measurement of many more functional
      traits than have been examined in previous studies.

PMID- 30238459
TI  - Effect of different sugars on the freezing characteristics of Kyoho grape.
AB  - The aim of this work was to analyze the effect of different osmotic dehydration
      (OD) processes (sucrose, trehalose, glucose, and lactose) as a pretreatment for
      grape before exposure to freezing. The osmotic treatment had less effect on
      blueberry moisture content among different sugars. Impregnation with sugars
      decreases the freezing time of grapes, compared to untreated grapes. Trehalose
      and lactose had a remarkable effect on shortening the time for grapes to pass the
      zone of maximum crystallization of ice. It was concluded that drip loss and
      electrolyte permeability of cell membranes decreased and the soluble solids
      content increased after OD treatment. In addition, the firmness and L* values of
      trehalose-treated grapes were significantly higher than those of other treatments
      (p < .05). In summary, osmosis with a carbohydrate solution not only increased
      the freezing rate but improved quality characteristics of grapes after freezing
      and thawing. PRACTICAL APPLICATIONS: Grapes are subject to freezing damage during
      storage, including significant water loss, berry softening, off flavor
      occurrence, which reduce the commodity and consumption of grapes. OD can improve
      the freezing rate by reducing the moisture content in the raw material and
      reducing the impact of freezing on the quality of fruits and vegetables, which
      may be beneficial to the process of freezing grapes.

PMID- 30238460
TI  - A method to estimate transmission profiles of bow-tie filters using rotating tube
      measurements.
AB  - PURPOSE: The purpose of this paper was to present a method of determining the
      dose profile of the beam bow-tie filter (BTF) without the need for fixing the x
      ray tube in a position or using special instruments or dosimeters other than the
      ordinary types of ion chambers used for CT dosimetry (e.g., Farmer chamber).
      METHODS: The idea behind this method is to try to invert the integral of
      exposures from axial measurements by decomposing it into fractions per degree of
      tube rotation. Measurements of the CT tube output were taken with a full tube
      rotation while the chamber was fixed in air. Starting with isocenter the output
      measurements were performed at 1-cm interval above the isocenter. Measurements
      were repeated for three sizes of BTFs; small, medium, and large. Maximum fan
      angle per chamber position was computed and an effective fan angle was defined to
      account for the new angular range encountered per chamber position. Variation due
      to inverse-square law was isolated from each measurement and contribution from
      the effective fan angle was computed. Resulted profiles from this method were
      then compared to profiles obtained with direct measurements, when the tube was in
      a fixed position. Effects of over and under 360 degrees  rotation per scan on
      results accuracy were also investigated. RESULTS: Using the direct measurements
      as the gold standard, results from this method were accurate to 4% for most of
      the BTFs angular ranges. The average relative error in the small BTF was 1.5%. In
      the medium BTF, the average relative error was <3% for up to 16 degrees  fan
      angle. With the large BTF, the mean error was about 4% for up to 22 degrees . The
      relative error appeared to increase at larger fan angles especially with the
      large BTF; reaching an average of about 32% for fan angles between 22 degrees 
      and 27.5 degrees . CONCLUSION: The presented method is relatively easy to perform
      and provides BTFs profiles with reasonably good accuracy. Associated errors of
      >10% only appear in high angles of large and medium BTFs.

PMID- 30238461
TI  - Survival analysis of caries incidence in African-American school-aged children.
AB  - OBJECTIVES: To conduct an assessment of time-dependent covariates related to
      dental caries of the permanent dentition among a low socioeconomic status,
      understudied cohort of children, incorporating time-dependent covariates through
      the application of extended Cox proportional hazards modeling. METHODS: This
      study modeled the time to first cavitated dental caries in permanent teeth among
      school-aged children and assessed factors associated with this event. A cohort of
      98 low socioeconomic status African-American children with mean age of 5.85 years
      at baseline was recruited in Uniontown, Alabama and followed prospectively for 6
      years. None of these children had dental caries on permanent teeth at baseline,
      and oral examinations were performed annually. Caries-free survival curves were
      generated to describe time to event (having first decayed, filled, or missing
      permanent surface). Bivariate and multivariable extended Cox hazards modeling was
      used to assess the relationships between time-dependent and time-independent
      covariates and time to event. RESULTS: Twenty-eight children (28.6 percent) had
      their first permanent tooth caries event during the 6-year follow-up.
      Multivariable results showed that greater consumption of water was associated
      with lower dental caries hazard, while previous primary tooth caries experience
      was associated with greater dental caries hazard after adjustment for frequency
      of consumptions of milk, added-sugar beverages, and 100 percent juice.
      CONCLUSIONS: There was a global/overall significant caries protective effect of
      water consumption during the school-age period of child development.

PMID- 30238462
TI  - Fluid-based proteomics targeted on pathophysiological processes and pathologies
      in neurodegenerative diseases.
AB  - Neurodegenerative dementias constitute a broad group of diseases in which
      abnormally folded proteins accumulate in specific brain regions and result in
      tissue reactions that eventually cause neuronal dysfunction and degeneration.
      Depending on where in the brain this happens, symptoms appear which may be used
      to classify the disorders on clinical grounds. However, brain changes in
      neurodegenerative dementias start to accumulate many years prior to symptom onset
      and there is a poor correlation between the clinical picture and what pathology
      that is the most likely to cause it. Thus, novel drug candidates having disease
      modifying effects that is targeting the underlying pathology and changes the
      course of the disease needs to be defined using objective biomarker-based
      measures since the clinical symptoms are often non-specific and overlap between
      different disorders. Furthermore, the treatment should ideally be initiated as
      soon as symptoms are evident or when biomarkers confirm an underlying pathology
      (pre-clinical phase of the disease) to reduce irreversible damage to, for
      example, neurons, synapses and axons. Clinical trials in the pre-clinical phase
      bring a greater importance to biomarkers since by definition the clinical effects
      are difficult or slow to discern in a population that is not yet clinically
      affected. Here, we discuss neuropathological changes that may underlie
      neurodegenerative dementias, including how they can be detected and quantified
      using currently available biofluid-based biomarkers and how more of them could be
      identified using targeted proteomics approaches.

PMID- 30238463
TI  - Increased tau phosphorylation follows impeded dopamine clearance in a P301L and
      novel P301L/COMT-deleted (DM) tau mouse model.
AB  - In Alzheimer's disease, the phosphorylation of tau is a critical event preceding
      the formation of neurofibrillary tangles. Previous work exploring the impact of a
      dopamine blocking antipsychotic on tau phosphorylation in a tau transgenic model
      suggested that extracellular dopamine may play a regulatory role in the
      phosphorylation state of tau. In order to test this hypothesis, and in order to
      develop a mouse model of impaired dopamine metabolism and tauopathy, an extant
      P301L transgenic tau model of Alzheimer's disease and a novel P301L/catechol-O
      methyltransferase deleted model (DM mouse) were treated with the norepinephrine
      reuptake inhibitor reboxetine, and prefrontal dopamine concentrations and the
      phosphorylated state of tau was quantified. In two experiments, male and female
      P301L+/+//COMT+/+ and P301L+/+//COMT-/- (DM) mice were treated with reboxetine 20
      mg/kg IP. In one experiment, acutely following reboxetine injection, the
      prefrontal cortex of mice were microdialyzed for dopamine, and its metabolites,
      3,4-dihydroxyphenylacetic acid and homovanillic acid, utilizing the MetaQuant
      technique. In another experiment, acutely following reboxetine injections, tau
      phosphorylation was quantified in the frontal cortex, striatum, and hippocampus
      of the mice. Reboxetine injections were followed by significant increases from
      baseline in extracellular dopamine concentrations in P301L and DM mice, with
      significantly higher peak levels in the DM mice. Treatment was also followed by
      increases in tau phosphorylation spread throughout brain regions, with a larger
      impact on female mice. Extracellular dopamine concentrations exert an influence
      on the phosphorylation state of tau, with surges in dopamine associating with
      acute increases in tau phosphorylation.

PMID- 30238464
TI  - The contribution of the individual blood elements to the variability of
      thromboelastographic measures.
AB  - BACKGROUND: Thromboelastography (TEG) is widely advocated as a rapid method for
      obtaining critical blood coagulation data to guide resuscitation, but the method
      suffers well-known limits in sensitivity, repeatability, and interpretability.
      STUDY DESIGN AND METHODS: Mixtures of fresh human blood components were prepared
      that represent the range of blood element concentrations seen in health and
      disease and after injury. These mixtures were tested in a TEG device after
      kaolin, tissue factor and phospholipid, or tissue factor and phospholipid with
      abciximab activation. The results were measured as reproducibility and nonlinear
      effects in regression analysis and evaluated for interpretability. RESULTS: Clot
      strength was associated with increased platelet (PLT) content and plasma
      fibrinogen concentration and content. Increasing hematocrit (Hct) reduced while
      increasing PLT or plasma concentration increased TEG clot strength. The abciximab
      dose used to block PLT activity did not fully inhibit the PLT contribution to
      clot strength. Clot strength is logarithmically correlated in the absence and
      linearly correlated to PLT concentration in the presence of abciximab. TEG clot
      strength with or without abciximab is dependent on Hct, PLT, and plasma
      (fibrinogen) concentrations in complex patterns. CONCLUSION: Interpretation of
      TEG variables is limited without knowledge of the concentration of the blood
      components present. When "normal" TEG values are known for a certain PLT-plasma
      red blood cell concentration, the assay can be used to assess PLT and plasma
      function in coagulation. The TEG "functional fibrinogen" assay should be used
      only as a gross estimate of the fibrinogen concentration in whole blood.

PMID- 30238465
TI  - Intolerance of uncertainty moderates the relations among religiosity and motives
      for religion, depression, and social evaluation fears.
AB  - OBJECTIVES: Intolerance of uncertainty (IU) underlies several psychological
      disorders, and religion may help some individuals cope with IU and/or protect
      against psychological symptoms. It was hypothesized that IU would moderate the
      relations between coping motives for being religious, as well as religiosity, and
      common psychological disorder symptoms: Depression and social evaluation fears.
      METHODS: Study 1 included 473 self-reporting community members (M age  = 48, 48%
      female, 80% Protestant/Catholic). Study 2 included 412 self-reporting
      undergraduates ( M age  = 19, 71% female, 76% Protestant/Catholic). RESULTS: For
      Study 1, coping-based motives related to greater depression for young adults with
      above-average IU and to lower depression for young adults with below-average IU.
      For Study 2, religiosity related to lower depression and fear of negative
      evaluation for individuals with above-average IU and to greater fear of positive
      evaluation for individuals with below-average IU. CONCLUSION: IU may be an
      important mechanism between aspects of religion and psychological disorder
      symptoms.

PMID- 30238466
TI  - Does ethnic identity buffer or intensify the stress of discrimination among the
      foreign born and U.S. born? Evidence from the Miami-Dade Health Survey.
AB  - This study examines the extent to which ethnic identity is a protective factor
      and buffers the stress of discrimination among the foreign born compared to the
      U.S. born in Miami-Dade County. Data were drawn from the 2011 Miami-Dade Health
      Survey (N = 444), which is a countywide probability sample of adults in South
      Florida. Two interaction effects were observed: (a) a stronger ethnic identity
      was associated with less distress among the foreign born than the U.S. born; and
      (b) a stronger ethnic identity exacerbated the relationship between everyday
      discrimination and distress among the U.S. born. Ethnic identity, which involves
      ethnic pride, participation in cultural practices, and cultural commitment or
      sense of belonging, was associated with better psychological well-being among the
      foreign born than the U.S. born. Ethnic identity, however, was not a protective
      factor for the U.S. born, but rather it intensified the distressing effect of
      discrimination.

PMID- 30238467
TI  - Human papillomavirus and oral and oropharyngeal carcinoma: the essentials.
AB  - There is a global increase in the prevalence of human papillomavirus (HPV)-driven
      oropharyngeal squamous cell carcinoma (OPSCC) in Australia and New Zealand. Risk
      factors for HPV-positive OPSCC are male gender, white race, age older than 40 but
      younger than 59 years old, having multiple lifetime sex partners, having oro
      genital and oro-anal sex. High-risk HPV subtypes play a major role in the
      pathogenesis of OPSCC, however, they play a much lesser role in oral squamous
      cell carcinoma (OSCC). Among the laboratory tests used to detect oncogenic HPV
      infection, polymerase chain reaction is a sensitive method but does not reflect
      the role of HPV in oncogenesis. While widely used, p16 immunohistochemistry is
      both a sensitive and a specific surrogate marker for oncogenic HPV infection in
      OPSCC, but not in OSCC. However, it is a useful prognostic marker in OPSCC. The
      current gold standard to accurately detect oncogenic HPV infection is E6/E7
      mRNAin situ hybridization. Because both HPV-positive and p16-positive OPSCC have
      better short-term prognoses there is current debate and trials on treatment de
      escalation in HPV-positive OPSCC. Dental practitioners can play an important role
      in early diagnosis of HPV-positive OPSCC.

PMID- 30238468
TI  - Allergic contact dermatitis caused by isopropyl lauroyl sarcosinate.

PMID- 30238469
TI  - Eugenol allergy mimicking burning mouth syndrome.

PMID- 30238470
TI  - Characterization of oral tactile sensitivity and masticatory performance across
      adulthood.
AB  - Texture perception is one of the most important factors in food acceptance, yet
      population-wide differences in texture sensations are not well understood. The
      variation in texture perception across populations is thought to depend on oral
      tactile sensitivity and masticatory performance. To address this hypothesis, we
      aimed to measure tactile acuity with a battery of tests and quantitate the
      relationship to masticatory performance. The study was performed on 98
      participants, in three age groups (20-25, 35-45, or over 62). Two main measures
      of oral sensitivity were performed: to assess bite force, subjects were asked to
      discriminate between foam samples of varying hardness. Second, to assess lingual
      sensitivity the subjects were asked to identify 3D printed shapes using their
      tongue, as well as identify confectionary letters. Additionally, masticatory
      performance was measured through assessing each participants ability to mix two
      colored chewing gum. In general, we found that sensitivity and masticatory
      performance in the younger age groups was superior to that of older adults. We
      also found a positive linear trend between bite force sensitivity and masticatory
      performance with younger participants, a trend not found in older participants.
      We found no significant relationship between age groups for bite force
      sensitivity and masticatory performance, suggesting that age-related declines in
      bite force sensitivity are not a significant cause of altered masticatory
      performance. This study represents a valuable first step in showing that bite
      force sensitivity does not depend on age, and the minimal influence of factors
      such as oral sensitivity on masticatory performance. PRACTICAL APPLICATIONS: In a
      society that is rapidly aging, it is important to understand the subtle changes
      in physiology and eating behavior that are associated with aging. This study used
      a variety of tests oral sensitivity to better understand which aspects of oral
      physiology are integral for effective chewing. The information gained helps shed
      light on to the factors that create an effective chewing cycle. Besides moving
      knowledge forward, this study may help in designing food and rehabilitation
      programs for those with trouble chewing and swallowing, increasing their overall
      quality of life.

PMID- 30238471
TI  - An HRP-labeled lateral flow immunoassay for rapid simultaneous detection and
      differentiation of influenza A and B viruses.
AB  - Rapid and sensitive diagnosis of influenza is urgently needed to address the
      limitations of low sensitivity associated with current rapid tests available for
      clinics and on-site monitoring. A novel horseradish peroxidase (HRP)-labeled
      lateral flow immunoassay strip (HRP-LFIA) for rapid simultaneous detection and
      differentiation of influenza A (INF A) and influenza B (INF B) viruses were
      developed. This immunoassay was based on the signal amplification by the HRP
      catalyzed oxidation of 3, 3', 5, 5'-tetramethylbenzidine forming a colored
      insoluble product, which was proportional to the analyte concentration. Compared
      with conventional gold-colloidal based strips, an analytical sensitivity
      enhancement of more than one order of magnitude for thirteen INF virus isolates
      was observed. A total of 1487 swabs obtained from persons with influenza-like
      illnesses were tested for the presence of INF A and B viruses using real-time
      reverse transcription polymerase chain reaction (rRT-PCR) as the reference
      criterion. The overall sensitivities of HRP-LFIA were 77.5% (100/129) and 71.2%
      (116/163) for INF A and INF B, respectively. The overall specificities were 99.8%
      (1144/1146) and 99.8% (918/920), respectively. The nasopharyngeal sampling method
      yielded higher sensitivity rates of 90.2% (55/61) and 82.6% (71/86). In
      conclusion, this user-friendly assay could be a promising rapid detection method
      for rapid screening of INF A and INF B viruses.

PMID- 30238472
TI  - Nitrate affects transcriptional regulation of UPBEAT1 and ROS localisation in
      roots of Zea mays L.
AB  - Nitrogen (N) is an indispensable nutrient for crops but its availability in
      agricultural soils is subject to considerable fluctuation. Plants have developed
      plastic responses to external N fluctuations in order to optimise their
      development. The coordinated action of nitric oxide and auxin seems to allow the
      cells of the root apex transition zone (TZ) of N-deprived maize to rapidly sense
      nitrate (NO3 - ). Preliminary results support the hypothesis that reactive oxygen
      species (ROS) signalling might also have a role in this pathway, probably through
      a putative maize orthologue of UPBEAT1 (UPB1). To expand on this hypothesis and
      better understand the different roles played by different root portions, we
      investigated the dynamics of ROS production, and the molecular and biochemical
      regulation of the main components of ROS production and scavenging in tissues of
      the meristem, transition zone, elongation zone and maturation zone of maize
      roots. The results suggest that the inverse regulation of ZmUPB1 and ZmPRX112
      transcription observed in cells of the TZ in response to nitrogen depletion or
      NO3 - supply affects the balance between superoxide (O2 *- ) and hydrogen
      peroxide (H2 O2 ) in the root apex and consequently triggers differential root
      growth. This explanation is supported by additional results on the overall
      metabolic and transcriptional regulation of ROS homeostasis.

PMID- 30238473
TI  - Partial amniotic carbon dioxide insufflation for fetal surgery.
AB  - Partial amniotic carbon dioxide insufflation (PACI) involves insufflating the
      amniotic sac with carbon dioxide (CO2 ) and, in some cases, draining some of the
      amniotic fluid. The creation of a gaseous intra-amniotic compartment improves
      visualization, even in the presence of limited bleeding, and creates the work
      space required for complex fetoscopic procedures. Clinically, PACI is mostly used
      to perform fetoscopic myelomeningocele (MMC) repair, enabling a minimally
      invasive alternative to open fetal surgery. However, evidence of the fetal safety
      of PACI is limited. Previous animal experiments in sheep demonstrate that PACI
      induces fetal hypercapnia and acidosis with largely unknown short and longer term
      implications. In this review, we examine the literature for the physiological
      effects of intrauterine insufflation pressure, duration, humidity, and the role
      of maternal hyperventilation on fetal physiology and well-being.

PMID- 30238474
TI  - Prion protein conversion triggered by acidic condition: a molecular dynamics
      study through different force fields.
AB  - Prions are proteins that cause a group of invariably fatal neurodegenerative
      diseases, one of the most known being bovine spongiform encephalopathy. The three
      dimensional structure of PrPSc , the altered isoform of the prion protein, has
      not been fully elucidated yet, and studies on prion conversion mechanisms must
      rely on hypothetical beta-rich structures. Experimental and computational studies
      indicate that the use of low pH is capable to produce a gain of beta-structure
      content in the otherwise unstructured N-terminal region. These in silico studies
      have used different PrP fragments from distinct organisms, and with different
      lengths and simulation protocols, making it difficult to identify the influence
      of the force fields on the formation of such structures. Here, we performed a
      systematic study of the influence of six well-established force fields (GROMOS96
      53a6, GROMOS96 43a1, AMBER99SB, AMBER99SB-ILDN, CHARMM27, and OPLS-AA/L) on the
      process of structural conversion of the Syrian hamster cellular prion protein
      simulated at acidic and neutral pH. From our analysis, we observe a strong
      dependence of the results with the different force fields employed. Additionally,
      only GROMOS96 53A6 and AMBER99SB force fields are capable to capture a high beta
      sheet formation at acidic pH and adequately reproduce the neutral pH. In both
      cases, the beta-sheet elongation seems to be guided by the movement of the N
      terminal tail toward the N-terminal of alpha-helix HB under acidic condition.
      These results comprise the most wide-ranging study to date correlating force
      fields to structural changes in the cellular prion protein. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30238475
TI  - Density functional tight binding-based free energy simulations in the DFTB+
      program.
AB  - The timescale problem-in which high barriers on the free energy surface trap
      molecular dynamics simulations in local energy wells-is a key limitation of
      current reactive MD simulations based on the density functional tight binding
      (DFTB) potential. Here, we report a new interface between the DFTB+ software
      package and the PLUMED library for performing DFTB-based free energy
      calculations. We demonstrate the performance of this interface for 3 archetypal
      rare-event chemical reactions, (i) intramolecular proton transfer in
      malonaldehyde, (ii) bowl inversion in corannulene, and (iii) oxygen diffusion on
      graphene. Using third-order DFTB in conjunction with metadynamics (with/without
      multiple walkers) and well-tempered metadynamics, we report here free energies of
      activation (DeltaG? ) of 13.1 +/- 0.4, 48.2 +/- 1.7, and 52.0 +/- 6.2 kJ mol-1 ,
      respectively, for these processes. In each case, our DFTB free energy barriers
      and local minima compare favorably with previous literature results,
      demonstrating the utility of the DFTB+ - PLUMED interface. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30238476
TI  - The role of protein disulphide isomerase AGR2 in the tumour niche.
AB  - In recent years, the discovery of 'tumour niche', a microenvironment that favours
      tumour development has changed our perspective of cancer. This microenvironment
      generated by the tumour cells itself and surrounding cells is capable of
      providing essential elements for its growth. Consequently, the homoeostasis of
      the secretory pathway (SP) has become an essential player in cancer development.
      The SP not only promotes cellular adaptation to protein misfolding due to
      oncogenic transformation or challenging tumour niche but also allows tumour cells
      to produce specific secretomes. This impacts tumour cells in cis- or trans- as
      well as stromal cells in the tumour niche. In this context, the Anterior GRadient
      2 (AGR2) protein has been identified as a key player. AGR2 is a protein
      disulphide isomerase that resides in the endoplasmic reticulum (ER) and mediates
      the formation of disulphide bonds, catalyses the cysteine-based redox reactions
      and assists the quality control of proteins. AGR2 not only plays an essential
      role in the homoeostasis of the SP but also exerts pro-oncogenic gain-of-function
      due to its reported mislocalisation in the tumour niche microenvironment. In this
      review, we summarise the dual role of AGR2, inside and outside the ER, on the
      tumour niche and its microenvironment.

PMID- 30238477
TI  - RAQET: Large-scale two-component relativistic quantum chemistry program package.
AB  - The Relativistic And Quantum Electronic Theory (RAQET) program is a new software
      package, which is designed for large-scale two-component relativistic quantum
      chemical (QC) calculations. The package includes several efficient schemes and
      algorithms for calculations involving large molecules which contain heavy
      elements in accurate relativistic formalisms. These calculations can be carried
      out in terms of the two-component relativistic Hamiltonian, wavefunction theory,
      density functional theory, core potential scheme, and evaluation of electron
      repulsion integrals. Furthermore, several techniques, which have frequently been
      used in non-relativistic QC calculations, have been customized for relativistic
      calculations. This article introduces the brief theories and capabilities of
      RAQET with several calculation examples. (c) 2018 Wiley Periodicals, Inc.

PMID- 30238478
TI  - Hydrolysis of chemically distinct sites of human serum albumin by
      polyoxometalate: A hybrid QM/MM (ONIOM) study.
AB  - In this study, mechanisms of hydrolysis of all four chemically diverse cleavage
      sites of human serum albumin (HSA) by [Zr(OH)(PW11 O39 )]4- (ZrK) have been
      investigated using the hybrid two-layer QM/MM (ONIOM) method. These reactions
      have been proposed to occur through the following two mechanisms: internal attack
      (IA) and water assisted (WA). In both mechanisms, the cleavage of the peptide
      bond in the Cys392-Glu393 site of HSA is predicted to occur in the rate-limiting
      step of the mechanism. With the barrier of 27.5 kcal/mol for the hydrolysis of
      this site, the IA mechanism is found to be energetically more favorable than the
      WA mechanism (barrier = 31.6 kcal/mol). The energetics for the IA mechanism are
      in line with the experimentally measured values for the cleavage of a wide range
      of dipeptides. These calculations also suggest an energetic preference (Cys392
      Glu393, Ala257-Asp258, Lys313-Asp314, and Arg114-Leu115) for the hydrolysis of
      all four sites of HSA. (c) 2018 Wiley Periodicals, Inc.

PMID- 30238479
TI  - Development and validation of a hydrophilic interaction ultra-high-performance
      liquid chromatography-tandem mass spectrometry method for rapid simultaneous
      determination of 19 free amino acids in rat plasma and urine.
AB  - Determination of amino acids in biofluids is a challenging task because of
      difficulties deriving from their high polarity and matrix interference. A simple,
      reliable and high-throughput hydrophilic interaction UHPLC-MS/MS method was
      developed and validated for the rapid simultaneous determination of 19 free amino
      acids in rat plasma and urine samples in this paper. Hydrophilic method with a
      Waters Acquity UPLC BEH Amide column (100 * 2.1 mm,1.7 MUm) was used with a
      gradient mobile phase system of acetonitrile and water both containing 0.2%
      formic acid. The analysis was performed on a positive electrospray ionization
      mass spectrometer via multiple reaction monitoring. Samples of 10 MUL plasma and
      50 MUL urine were spiked with three deuterated internal standards, pretreated
      with 250 MUL acetonitrile for one-step protein precipitation and a final dilution
      of urine samples. Good linearities (r > 0.99) were obtained for all of the
      analytes with the lower limit of quantification from 0.1 to 1.2 MUg/mL. The
      relative standard deviation of the intra-day and inter-day precisions were within
      15.0% and the accuracy ranged from -12.8 to 12.7%. The hydrophilic interaction
      UHPLC-MS/MS method was rapid, accurate and high-throughput and exhibited better
      chromatography behaviors than the regular RPLC methods. It was further
      successfully applied to detect 19 free amino acids in biological matrix.

PMID- 30238480
TI  - UPLC-MS/MS determination of flavokawain B, a novel anti-tumor chemotherapeutic
      agent in rat plasma and its application to a pharmacokinetic study in rats.
AB  - A sensitive, selective and rapid ultra-performance liquid chromatography/tandem
      mass spectrometry method was developed and validated for the quantification of
      flavokawain B in rat plasma using myrislignan as an internal standard. Sample
      preparation was accomplished through a protein precipitation extraction process.
      Chromatographic resolution of flavokawain B and the IS was achieved on an Agilent
      XDB-C18 column (2.1 * 100 mm, 1.8 MUm) using a gradient mobile phase comprising
      0.1% formic acid in water and acetonitrile delivered at a flow rate of 0.5
      mL/min. Flavokawain B and the IS eluted at 3.27 and 1.96 min, respectively. The
      total chromatographic run time was 6.0 min. A linear response function was
      constructed in the concentration range 0.524-1048 ng/mL. Method validation was
      performed as per the US Food and Drug Administration guidelines and the results
      met the acceptance criteria. Intra- and inter-day accuracy and precision were in
      the ranges of -14.3-13.2 and 3.4-11.8%, respectively. Flavokawain B was
      demonstrated to be stable under various stability conditions. This method has
      been applied to a pharmacokinetic study in rats.

PMID- 30238481
TI  - Determination of Penicillium griseofulvum-oriented pyripyropene A, a selective
      inhibitor of acyl-coenzyme A:cholesterol acyltransferase 2, in mouse plasma using
      liquid chromatography-tandem mass spectrometry and its application to
      pharmacokinetic studies.
AB  - In this study, we developed a method for the determination of Penicillium
      griseofulvum-oriented pyripyropene A (PPPA), a selective inhibitor of acyl
      coenzyme A:cholesterol acyltransferase 2, in mouse and human plasma and validated
      it using liquid chromatography-tandem mass spectrometry. Pyripyropene A (PPPA)
      and an internal standard, carbamazepine, were separated using a Xterra MS C18
      column with a mixture of acetonitrile and 0.1% formic acid as the mobile phase.
      The ion transitions monitored in positive-ion mode [M + H]+ of multiple-reaction
      monitoring (MRM) were m/z 148.0 from m/z 584.0 for PPPA and m/z 194.0 from m/z
      237.0 for the internal standard. The detector response was specific and linear
      for PPPA at concentrations within the range from 1 to 5,000 ng/mL. The intra
      /inter-day precision and accuracy of the method was acceptable by the criteria
      for assay validation. The matrix effects of PPPA ranged from 97.6 to 104.2% and
      from 93.3 to 105.3% in post-preparative mouse and human plasma samples,
      respectively. PPPA was also stable under various processing and/or handling
      conditions. Finally, PPPA concentrations in the mouse plasma samples could be
      measured after intravenous, intraperitoneal, or oral administration of PPPA,
      suggesting that the assay is useful for pharmacokinetic studies on mice and
      applicable to human studies.

PMID- 30238482
TI  - Inequality trends in the demographic and geographic distribution of health care
      professionals in China: Data from 2002 to 2016.
AB  - China has long been negatively affected by a shortage and maldistribution of
      health workers. This study aimed to examine the national and regional trends in
      the demographic and geographic distribution inequality of health care
      professionals in China from 2002 to 2016. Based on data from the China Health and
      Family Planning Statistical and China Statistical Yearbooks, we calculated the
      Gini coefficient and the Theil T and Theil L indices based on the number of
      health care professionals per capita and per geographic area to measure the
      inequalities in their demographic and geographic distribution, respectively. The
      contributions by intra-regional and inter-regional differences on total
      inequality were explored within and among East, Central, and West China via Theil
      index decomposition. We found that the national demographic distribution of
      health care professionals maintained in an absolute equality level, and the
      inequality indices decreased gradually, whereas the corresponding geographic
      inequalities were severe and presented a worsening trend. Compared with nurses,
      physicians not only maintained higher densities but also maintained a more equal
      distribution. Intra-regional disparities within the east, central, and western
      regions were the main cause for overall demographic inequality, whereas both
      intra-regional and inter-regional disparities significantly contributed to
      overall geographic inequality. To conclude, the distribution equality of health
      care professionals by population was satisfactory, whereas the corresponding
      distribution inequality by area was severe. Different types of distribution
      inequality of health care professionals existed regionally and nationally despite
      their increasing quantities and densities. Factors beyond population size should
      be considered when the government introduces health workforce allocation
      policies.

PMID- 30238483
TI  - Adapt your shuttling proteins for virulence: a lesson from the corn smut fungus
      Ustilago maydis.

PMID- 30238484
TI  - Chun-Peng Song.

PMID- 30238485
TI  - We are family: kin recognition in crop plants.

PMID- 30238486
TI  - Methods for the Simulation of the Slowing of Low-Energy Electrons in Water.
AB  - A computational Monte Carlo simulation approach for modeling the thermalization
      of low-energy electrons is presented. The simulation methods rely on, and use,
      experimentally based cross sections for elastic and inelastic collisions. To
      demonstrate the different simulation options, average numbers of interactions and
      the range of low-energy electrons with initial energies ranging from 1 to 20 eV
      are calculated for density normalized gaseous water. Experimental gas-phase cross
      sections for (subexcitation) electrons of energies in the range of 1-20 eV were
      taken from the compilation of Hayashi. The ballistic collision-by-collision
      simulations provide information on the intricacies of the thermalization
      processes not available experimentally. (c) 2018 Wiley Periodicals, Inc.

PMID- 30238487
TI  - Treatment of drooling with scopolamine in pediatric ICU: A case series report.
AB  - Drooling is a condition that affects patients with difficulties in swallowing,
      being common in patients with mental, neurological or dysphagic deficiency. This
      condition is difficult to diagnose, as it is often confused with sialorrhea, and
      in many cases we have a hyposalivation scenario. Its diagnosis is subjective,
      which is why scales should be used for the standardization of the evaluation of
      the degree of drooling before and after the proposed treatment, as the Thomas
      Stonell and Greenberg scale. It causes problems such as perioral infections,
      rashes, wet clothing, leading to social embarrassment, and may be a risk factor
      for respiratory infections caused by asymptomatic aspiration of saliva. It
      presents several treatments, among them the pharmacological one, that is
      dependent of the clinical picture of each patient that must be evaluated daily.
      This article refers to a series of reports of cases of children in mechanical
      ventilation by tracheostomy, hospitalized, with clinical diagnosis of drooling,
      and clinical improvement with the use of scopolamine by gastrostomy, without
      intercurrences during its use. The objective of this study is to show other
      professionals the importance of drooling management, and to expose the adopted
      behavior in the described cases, providing reduction of respiratory infections
      and improvement of the clinical and social complications resulting from drooling.

PMID- 30238488
TI  - Screening for production of proteinase inhibitors by Antarctic Streptomycetes.
AB  - Three out of 17 Streptomycetes strains - Streptomyces sp. 35 LBG09, Streptomyces
      sp. 36 LBG09, and Streptomyces sp. 39 LBG09, were selected based on the high
      production of proteinase inhibitors with trypsin serine proteinase activity. The
      strains were isolated from soil samples taken from the area around the Bulgarian
      station on Livingston Island, Antarctica. Biosynthesis of proteinase inhibitors
      by the promising strains started at different stages of their development but was
      generally not associated with the growth of the producers. Peak levels were
      reached in the stationary phase (96-120 h) of their cultivation. Inducing effects
      on strain development, biomass accumulation, and proteinase inhibitor
      biosynthesis were based on the composition of the nutrient medium: the
      polypeptones contained in Taguchi medium and glucose as a carbon source. The most
      productive out of the three strains was Streptomyces sp. 36 LBG09. Its maximum
      inhibitory activity was reached at 96 h in culturing media modified by three
      different carbon sources. The active proteinase inhibitor biosynthesis proceeded
      at pH values between 6.8 and 8.6 and the dynamics of production depended on the
      type of carbon source. Peak levels of extracellular protein and dry biomass were
      reached at 120 h in the stationary growth phase. The residual sugars were minimal
      at the end of the process when using soluble starch as a carbon source, and
      maximal when glucose was used.

PMID- 30238489
TI  - Development of a method for quantitative determination of the cytotoxic agent
      piplartine (piperlongumine) in multiple skin layers.
AB  - This study reports the development of a simple and reproducible method, with high
      rates of recovery, to extract the cytotoxic agent piplartine from skin layers,
      and a sensitive and rapid UV-HPLC method for its quantification. Considering the
      potential of piplartine for topical treatment of skin cancer, this method may
      find application for formulation development and pharmacokinetics studies to
      assess cutaneous bioavailability. Porcine skin was employed as a model for human
      tissue. Piplartine was extracted from the stratum corneum (SC) and remaining
      viable skin layers (VS) using methanol, vortex homogenization and bath
      sonication, and subsequently assayed by HPLC using a C18 column, and 1:1 (v/v)
      acetonitrile-water (adjusted to pH 4.0 with acetic acid 0.1%) as mobile phase.
      The quantification limit of piplartine was 0.2 MUg/mL (0.6 MUm), and the assay
      was linear up to 5 MUg/mL (15.8 MUm), with within-day and between-days assay
      coefficients of variation and relative errors <15%. Piplartine recovery from SC
      and VS varied from 86 to 96%. The method was suitable to assay samples from skin
      penetration studies, enabling detection of differences in cutaneous delivery in
      different skin compartments resulting from treatment with various formulations
      and time periods.

PMID- 30238491
TI  - Language Matters - but so does the philosophy.

PMID- 30238490
TI  - Financing health care in Bangladesh: Policy responses and challenges towards
      achieving universal health coverage.
AB  - Bangladesh has attained notable progress in most of the health indicators, but
      still, health system of the country is suffering badly from poor funding. Issues
      like burden of out-of-pocket expenditure, low per capita share in health,
      inadequate service facilities, and financial barriers in reducing malnutrition
      are being overlooked due to inadequacy and inappropriate utilization of allocated
      funds. We aimed to review the current status of health care spending in
      Bangladesh in response to national health policy (NHP) and determine the future
      challenges towards achieving universal health coverage (UHC). National health
      policy suggested a substantial increase in budgetary allocation for health care,
      although government health care expenditures in proportion to total public
      spending plummeted down from 6.2% to 4.04% in the past 8 years. Overall, 67% of
      the health care cost is being paid by people, whereas global standard is below
      32%. Only one hospital bed is allocated per 1667 people, and 34% of total posts
      in health sector are vacant due to scarcity of funds. The country is experiencing
      demographic dividend with a concurrent rise of aged people, but there seems no
      financial protection schemes for the aged and working age populations. Such
      situation results in multiple obstacles in achieving financial risk protection as
      well as UHC. Policy makers must think effectively to develop and adapt systems in
      order to achieve UHC and ensure health for all.

PMID- 30238492
TI  - Investigation of an outbreak caused by antibiotic-susceptible Klebsiella oxytoca
      in a neonatal intensive care unit in Norway.
AB  - AIM: Klebsiella spp. have been stated to be the most frequent cause of neonatal
      intensive care unit (NICU) outbreaks. We report an outbreak of Klebsiella oxytoca
      in a NICU at a tertiary care hospital in Norway between April 2016 and April
      2017. This study describes the outbreak, infection control measures undertaken
      and the molecular methods developed. METHODS: The outbreak prompted detailed
      epidemiological and microbial investigations, where whole-genome sequencing (WGS)
      was particularly useful for both genotyping and development of two new K. oxytoca
      specific real-time PCR assays. Routine screening of patients, as well as sampling
      from numerous environmental sites, was performed during the outbreak. A bundle of
      infection control measures was instigated to control the outbreak, among them
      strict cohort isolation. RESULTS: Five neonates had symptomatic infection, and 17
      were found to be asymptomatically colonised. Infections varied in severity from
      conjunctivitis to a fatal case of pneumonia. A source of the outbreak could not
      be determined. CONCLUSION: This report describes K. oxytoca as a significant
      pathogen in a NICU outbreak setting and highlights the importance of developing
      appropriate microbiological screening methods and implementing strict infection
      control measures to control the outbreak in a setting where the source could not
      be identified.

PMID- 30238493
TI  - Enantioseparation of chiral mandelic acid derivatives by supercritical fluid
      chromatography.
AB  - Mandelic acid and its derivatives are important chiral analogs which are widely
      used in the pharmaceutical synthetic industry. The present study investigated the
      enantiomeric separation of six mandelic acids (mandelic acid, 2-chloromandelic
      acid, 3-chloromandelic acid, 4-chloromandelic acid, 4-bromomandelic acid, 4
      methoxymandelic acid) on the Chiralpak AD-3 column by supercritical fluid
      chromatography. The influences of volume fraction of trifluoroacetic acid, type
      and percentage of modifier, column temperature, and backpressure on the
      separation efficiency were investigated. And the enantiomer elution order was
      determined. The results show that, for a given modifier, the retention factor,
      the separation factor, and the separation resolution decreased gradually with
      increasing the volume ratio of the modifier. At the same volume ratio of
      modifier, the retention factor of the mandelic acid and its derivatives increased
      in the order of methanol, ethanol, and isopropanol, except 3-chloromandelic acid.
      The separation factor and the separation resolution decreased with the increase
      of column temperature (below the temperature limit). The backpressure affected
      the enantioseparation process: As the backpressure increased, a corresponding
      decrease in retention factor was observed. Under the same chiral column
      conditions, the SFC method exhibited faster and more efficient separation with
      better enantioselectivity than the HPLC method.

PMID- 30238494
TI  - A qualitative study of attitudes to and perceptions of betel quid consumption and
      its oral health implications in Taiwan.
AB  - OBJECTIVES: Betel quid (BQ) chewing is extremely prominent in South and Southeast
      Asia because it considered by users to be of social, cultural and religious
      importance. BQ chewing has been recognized as a risk factor for oral premalignant
      lesions and oral cancer. Because BQ chewing has become a severe health risk in
      Taiwan, the development of prevention and cessation programmes is essential. The
      purpose of this study was to explore the attitudes and perceptions associated
      with BQ consumption and its oral health implications in an attempt to inform the
      development of health promotion initiatives and BQ cessation efforts in Taiwan,
      where the dental profession could have a pivotal role in preventing and
      controlling BQ use among persons at risk. METHODS: This qualitative study used
      data gathered from focus groups and individual interviews. A convenience sample
      of 41 adults from Jhushan and Lugu Townships (Nantou County) and Taichung City,
      Taiwan, participated in this study (27 men, 14 women; 31 Han, 10 aboriginals from
      the Paiwan tribe; mean age 40.3, SD 9.2 years). RESULTS: Among the seven themes
      that emerged from the original study, five (Initiation, Health Risk Perception,
      Health Consequences, Withdrawal Symptoms and Help from Healthcare Providers) had
      oral/dental implications. CONCLUSIONS: Our study highlights research areas
      relevant to further investigation, such as incorporating brief BQ prevention and
      cessation counselling when early oral and dental signs associated with BQ
      consumption are detected. Undertaking behavioural interventions in dental
      settings might help to reduce the prevalence of BQ chewing in Taiwan.

PMID- 30238495
TI  - Health insurance in Myanmar: Knowledge, perceptions, and preferences of Social
      Security Scheme members and general adult population.
AB  - OBJECTIVE: Our study explores the knowledge, perceptions, willingness to pay, and
      preferences of potential health insurance beneficiaries about health insurance in
      Myanmar. METHODS: Cross-sectional survey data were collected among two samples:
      the general population and Social Security Scheme (SSS) member. Mann-Whitney U
      test and independent sample t test were applied to compare the two samples. The
      data on willingness to pay for health insurance were analyzed using regression
      analysis. RESULTS: Low level of knowledge and weak positive perception are found
      in both samples. More than 90% of the SSS sample and 75% of the general sample
      are willing to pay health insurance premiums. The largest shares of both samples
      are willing to pay for monthly premiums between 2000 and 4000 MMK (1.8-3.6 USD).
      Health status, age, gender, income, and trust are significantly associated with
      willingness to pay for health insurance among general sample while occupation,
      civil status, income, and positive perception on prepayment principle are found
      among SSS sample. CONCLUSIONS: The government of Myanmar should be aware of the
      preferences of beneficiaries to pay a relatively low level of monthly health
      insurance premiums without co-payment.

PMID- 30238497
TI  - Development and validation of serum exosomal microRNAs as diagnostic and
      prognostic biomarkers for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related
      death worldwide. China accounts for over half of the new cases and deaths.
      Diagnostic imprecision and a lack of complimentary molecular biomarkers are
      partially responsible for this lack of progress. Herein, serum-derived exosomal
      microRNA (miRNA) profiling was performed on 80 patients which histologically
      confirmed HCC and 30 normal controls. A classification of 8 exosomal miRNAs had
      biologically and statistically significant differences between HCC and normal
      serum samples, including miR-122, miR-125b, miR-145, miR-192, miR-194, miR-29a,
      miR-17-5p, and miR-106a. Online algorithm showed strong independent
      classification accuracy (area under the curve) reached 0.535 to 0.850,
      separately. The significant correlation between serum exosomal miRNAs and tumor
      size was observed. In addition, the survival difference of HCC patients with high
      or low exosomal miR-106a was statistically significant using Kaplan-Meier
      analysis. Besides, we also measured the proliferation and invasion ability of HCC
      cells following exosomal miR-106a mimics or inhibitor treatment. After prediction
      with algorithms, mitogen-activated protein kinase and c-Jun N-terminal kinase
      pathways were identified associated with miR-106a's function. In summary,
      differentially expressed serum exosomal miRNAs can be helpful for diagnostic and
      prognostic of HCC.

PMID- 30238496
TI  - Adjustment for covariates using summary statistics of genome-wide association
      studies.
AB  - Linear regression is a standard approach to identify genetic variants associated
      with continuous traits in genome-wide association studies (GWAS). In a standard
      epidemiology study, linear regression is often performed with adjustment for
      covariates to estimate the independent effect of a predictor variable or to
      improve statistical power by reducing residual variability. However, it is
      problematic to adjust for heritable covariates in genetic association analysis.
      Here, we propose a new method that utilizes summary statistics of the covariate
      from additional samples for reducing the residual variability and hence improves
      statistical power. Our simulation study showed that the proposed methodology can
      maintain a good control of Type I error and can achieve much higher power than a
      simple linear regression. The method is illustrated by an application to the GWAS
      results from the Genetic Investigation of Anthropometric Traits consortium.

PMID- 30238499
TI  - In remembrance of Peter Brussard.

PMID- 30238498
TI  - Microscopy of Gram-stained urethral smear in the diagnosis of urethritis: Which
      threshold value should be selected?
AB  - The aim of this study was to investigate the sensitivity of GSS in the diagnosis
      of urethritis in patients who present to the outpatient clinic with symptoms of
      urethritis. Sixty-three male patients who presented to our outpatient clinic with
      symptoms of urethritis between January and March 2018 were evaluated. Urethral
      smear samples obtained from patients were evaluated both by GSS examination and
      by Real-time Multiplex Polymerase Chain Reaction (rt-MPCR) assay. The sensitivity
      and specificity of GSS in detecting gonococcal urethritis (GU) and nongonococcal
      urethritis (NGU) were calculated for threshold values of >=5 and >=2 PMNL/HPF.
      The mean age was 33.2 +/- 7.1 years. According to the rt-MPCR results, 14
      patients had GU and 27 patients had NGU. A threshold value of >=5 PMNL/HPF in the
      GSS demonstrated 92.9% sensitivity in the diagnosis of GU and 55.6% sensitivity
      in the diagnosis of NGU. A threshold value of >=2 PMNL/HPF reached 100%
      sensitivity for GU and 92.6% sensitivity for NGU. A cut-off value of >=5 PMNL/HPF
      in the GSS has low sensitivity in the diagnosis of NGU. On the other hand, a
      threshold value of >=2 PMNL/HPF seems to have higher sensitivity in the diagnosis
      of both GU and NGU.

PMID- 30238500
TI  - Closing a window - opening a door: A response to the letter to the editor.
AB  - In this response, the authors of "A meta-analysis of anatomy laboratory
      pedagogies" (Wilson, 2018) make counter arguments to a letter submitted to the
      editor while encouraging academicians to consider a more modern perspective of
      anatomy education in the context of changing curricular models. While the authors
      agree the dissection laboratory is fertile ground for cultivating professional
      skill development, in more modern settings there are a myriad of outlets and
      experiences through which trainees can gain the necessary exposure to the same
      professional skills which are often touted as being informally developed in the
      anatomy laboratory. Overall, the authors advocate for closing the window on
      evaluating short-term anatomy knowledge outcomes so that the door can be opened
      to evaluating the effects of dissection on long-term knowledge gains and
      determining whether there are irreplaceable teaching advantages within
      hidden/informal curricula in the anatomy laboratory. Clin. Anat., 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 30238501
TI  - Comprehensive screening shows that mutations in the known syndromic genes are
      rare in infants presenting with hyperinsulinaemic hypoglycaemia.
AB  - OBJECTIVE: Hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or more
      rarely feature as part of a syndrome. Screening for mutations in the "syndromic"
      HH genes is guided by phenotype with genetic testing used to confirm the clinical
      diagnosis. As HH can be the presenting feature of a syndrome, it is possible that
      mutations will be missed as these genes are not routinely screened in all newly
      diagnosed individuals. We investigated the frequency of pathogenic variants in
      syndromic genes in infants with HH who had not been clinically diagnosed with a
      syndromic disorder at referral for genetic testing. DESIGN: We used genome
      sequencing data to assess the prevalence of mutations in syndromic HH genes in an
      international cohort of patients with HH of unknown genetic cause. PATIENTS: We
      undertook genome sequencing in 82 infants with HH without a clinical diagnosis of
      a known syndrome at referral for genetic testing. MEASUREMENTS: Within this
      cohort, we searched for the genetic aetiologies causing 20 different syndromes
      where HH had been reported as a feature. RESULTS: We identified a pathogenic
      KMT2D variant in a patient with HH diagnosed at birth, confirming a genetic
      diagnosis of Kabuki syndrome. Clinical data received following the identification
      of the mutation highlighted additional features consistent with the genetic
      diagnosis. Pathogenic variants were not identified in the remainder of the
      cohort. CONCLUSIONS: Pathogenic variants in the syndromic HH genes are rare;
      thus, routine testing of these genes by molecular genetics laboratories is
      unlikely to be justified in patients without syndromic phenotypes.

PMID- 30238502
TI  - Detecting deterrence from patrol data.
AB  - The threat posed to protected areas by the illegal killing of wildlife is
      countered principally by ranger patrols that aim to detect and deter potential
      offenders. Deterring poaching is a fundamental conservation objective, but its
      achievement is difficult to identify, especially when the prime source of
      information comes in the form of the patrols' own records, which inevitably
      contain biases. The most common metric of deterrence is a plot of illegal
      activities detected per unit of patrol effort (CPUE) against patrol effort (CPUE
      E). We devised a simple, mechanistic model of law breaking and law enforcement in
      which we simulated deterrence alongside exogenous changes in the frequency of
      offences under different temporal patterns of enforcement effort. The CPUE-E
      plots were not reliable indicators of deterrence. However, plots of change in
      CPUE over change in effort (DeltaCPUE-DeltaE) reliably identified deterrence,
      regardless of the temporal distribution of effort or any exogenous change in
      illegal activity levels as long as the time lag between patrol effort and
      subsequent behavioral change among offenders was approximately known. The
      DeltaCPUE-DeltaE plots offered a robust, simple metric for monitoring patrol
      effectiveness; were no more conceptually complicated than the basic CPUE-E plots;
      and required no specialist knowledge or software to produce. Our findings
      demonstrate the need to account for temporal autocorrelation in patrol data and
      to consider appropriate (and poaching-activity-specific) intervals for
      aggregation. They also reveal important gaps in understanding of deterrence in
      this context, especially the mechanisms by which it occurs. In practical
      applications, we recommend the use of DeltaCPUE-DeltaE plots in preference to
      other basic metrics and advise that deterrence should be suspected only if there
      is a clear negative slope. Distinct types of illegal activity should not be
      grouped together for analysis, especially if the signs of their occurrence have
      different persistence times in the environment.

PMID- 30238503
TI  - Inpatient toxicology services improve resource utilization for intoxicated
      patients: a systematic review.
AB  - AIMS: Presentations of intoxicated patients to hospital are frequent and
      increasing. We aimed to review the existing evidence that the presence of
      inpatient clinical toxicology services reduces use of resources without impacting
      on the care of these patients. METHODS: We conducted a literature search using
      the Cochrane Library, PubMed, and Embase for articles that measured length of
      stay (and other outcomes) for the target population, with toxicology services as
      an intervention. The articles were reviewed with respect to the ROBINS-I tool.
      RESULTS: Seven relevant articles were identified. Six of these studies
      demonstrated reduced hospital length of stay for intoxicated patients in
      hospitals with inpatient toxicology services. None of the articles demonstrated a
      detriment in morbidity or mortality. There were also improvements in other
      resource-related outcomes. CONCLUSIONS: The presence of inpatient toxicology
      services appears to improve resource utilization, in reduction of length of stay,
      as well as a number of other related outcomes. It does this without compromising
      on patient morbidity or mortality. Thus, it should be considered as a potential
      model of care for future toxicology services, especially with current trends of
      increasing demand for service efficiency.

PMID- 30238505
TI  - Synthesis of chiral salalen ligands and their in-situ generated Cu-complexes for
      asymmetric Henry reaction.
AB  - Chiral salalen ligands derived from (S)-proline and derivatives of
      salicyaldehydes were synthesized, and their in-situ generated Cu (II) complexes
      were evaluated in the asymmetric Henry reaction. Salalen ligand of different
      substituents on the phenyl moiety showed remarkable effect on the
      enantioselectivity of nitro-aldol product of 4-nitrobenzaldehyde and
      nitromethane. Cu (II) complex generated in situ with (S)-2-(tert-butyl)-6-((2
      (((2-hydroxy-3-methylbenzylidene)amino)methyl)pyrrolidin-1-yl)methyl) phenol (10
      mol%) and Cu (OAc)2 .H2 O (10 mol%), found to be better catalyst for nitro-aldol
      reaction between 4-nitrobenzaldehyde and nitromethane, gave corresponding product
      in 85% yield and 88% enantiomeric excess (ee) in isopropanol at 35 degrees C
      after 40 hours. The catalyst also used for the Henry reaction with different
      substituted benzaldehydes and corresponding products were obtained in 22% to 99%
      yields with 66% to 92% ee. Henry reaction of 4-nitrobenzaldehyde and prochiral
      nitroethane gave anti-selective product (dr = 79/21; anti/syn) in a 91% yield
      with 80% ee.

PMID- 30238504
TI  - Enantioselective toxic effects and digestion of furalaxyl enantiomers in
      Scenedesmus obliquus.
AB  - Research on the enantioselective environmental behavior of chiral pesticides has
      been a hot spot of environmental chemistry recently. In this study, the acute
      toxicity and digestion of furalaxyl enantiomers were determined on the aquatic
      algae Scendesmus obliquus. After exposure for 96 hours, the EC50 values for (S)
      furalaxyl and (R)-furalaxyl were 13.59 and 15.26 mg/L, respectively. In addition,
      enantioselectivity was observed from the determined chlorophyll contents and
      antioxidant enzyme (CAT and SOD) activities of algae cells after exposure to
      furalaxyl enantiomers for 96 hours. The digestion rate of (S)-furalaxyl and (R)
      furalaxyl were almost the same in S. obliquus. On the basis of these data, the
      inactive enantiomers (S)- furalaxyl is more toxic than the active one on the non
      target species S. obliquus, indicating that such enantiomeric differences should
      be taken into consideration in the study of pesticide risk assessment.

PMID- 30238506
TI  - Rural-urban disparities in family physician practice patterns: A nationwide
      survey in Taiwan.
AB  - INTRODUCTION: In a world with increasing urbanization, rural-urban disparities in
      health care utilization have been a long-term concern. However, the details
      regarding the practice patterns of family physicians in Taiwan have not received
      sufficient attention thus far. METHODS: The National Health Insurance Research
      Database of Taiwan offered 0.2% of the total ambulatory visit records for Taiwan
      in 2013. Records from community clinics of family medicine were collected, with
      the clinics categorized as rural, suburban, or urban area clinics according to
      their locations. RESULTS: Among 100 334 visits to family medicine clinics, the
      median patient age was 50 years for urban clinics, 51 for suburban clinics, and
      58 for rural clinics. The distributions of patient ages differed in the three
      areas (P < 0.001). Four types of chronic diseases (cardiovascular diseases,
      diabetes, chronic respiratory diseases, and cancers) accounted for 10.8%, 11.3%,
      and 13.6%, of the visits to urban, suburban, and rural clinics, respectively. The
      most common procedure was wound treatment, and the pattern of the top 10
      procedures was similar in the three areas. CONCLUSION: Although rural patients in
      Taiwan were older and had more chronic diseases than urban and suburban patients,
      the pattern of procedures undertaken by rural family physicians did not differ
      from those of urban and suburban family physicians.

PMID- 30238507
TI  - Comparison of actinomycin peptide synthetase formation in Streptomyces
      chrysomallus and Streptomyces antibioticus.
AB  - Actinomycin peptide synthetase genes constitute two oppositely oriented
      transcriptional units, acmADR, and acmBC, separated by a non-coding intergenic
      region. Gene constructs of the intergenic region together with its adjoining gene
      acmA or acmB from the actinomycin biosynthetic gene cluster of Streptomyces
      chrysomallus were transferred into Streptomyces lividans TK64. Each construct
      expressed the respective synthetase indicating divergent promoters. Primer
      extension revealed for both directions -10 and -35 boxes similar to sigma70 
      dependent promoters from Streptomyces and E. coli. No conspicuous regulatory
      sequences were detected. Accordingly, S. chrysomallus-grown in glucose-containing
      medium-produced the peptide synthetases AcmA and AcmB/C as well as actinomycin
      during logarithmic growth phase. Alignments with the corresponding intergenic
      region of the actinomycin biosynthetic gene cluster in Streptomyces antibioticus
      identified analogous -10 and -35 boxes of sigma70 consensus sequence. However, in
      S. antibioticus-cultivated in the same conditions-AcmA and AcmB/C were at maximum
      activity in late log phase and actinomycin formation peaked in stationary phase.
      The different patterns of formation of actinomycin and its peptide synthetases
      encoded by the highly homologous actinomycin biosynthetic gene clusters in S.
      chrysomallus and S. antibioticus suggest strain-specific control of biosynthesis
      in agreement with absence of pathway-specific regulatory genes.

PMID- 30238508
TI  - Identifying and confirming demotivating factors for village health workers in
      rural communities of Bhutan.
AB  - BACKGROUND: Bhutan achieved over 95% of health coverage through its primary
      health care network and geared towards achieving and ensuring Universal Health
      Coverage. About 62.2% of the Bhutanese people are rural dwellers, living in
      villages. Village health workers (VHWs) are essential for primary health care
      delivery at the community level in order to bridge the gap between the health
      care system and the communities. However, increasing numbers of VHWs leaving the
      health care system remain a challenge for Bhutan. This study intends to find
      existing problems of motivation and retention among VHWs in Bhutan and to devise
      appropriate strategies for making effective policy interventions. METHODS: This
      quantitative study with a cross-sectional survey design aims to determine
      demotivating factors. One stage cluster sampling technique was applied for VHWs
      from 12 districts in three regions. Data were collected by the trained
      enumerators using a pre-tested semi-structured questionnaire. RESULTS: The
      Confirmatory factor analysis identified and confirmed a four-factor model of
      demotivation among VHWs in Bhutan. Among the four factors, the social factor was
      the main factor for VHWs leaving the health care system. However, the holistic
      combination of both financial and non-financial motivator needs to be taken into
      consideration. The content analysis revealed six areas of recommendation for
      improving motivation and retention among VHWs. CONCLUSION: The study concluded
      that managers and policymakers must give more emphasis to non-financial
      motivators through the holistic approach to existing altruism and intrinsic
      needs.

PMID- 30238509
TI  - Why and when does job satisfaction promote unethical pro-organizational
      behaviours? Testing a moderated mediation model.
AB  - This study examined the relationship between job satisfaction and unethical pro
      organizational behaviours (UPB) by testing a moderated mediation model that
      focused on how employees' belongingness mediates the relationship between job
      satisfaction and UPB and how corporate ethical values moderate this mediated
      relationship. Our investigation included 369 employees from different
      organizations in Southeast China. The regression analysis revealed that job
      satisfaction positively influences UPB through belongingness. In addition, a
      moderated regression analysis indicated that low corporate ethical values
      strengthen not only the effect of belongingness on UPB but also the indirect
      effect of job satisfaction on UPB. These findings deepen our understanding of UPB
      by showing that individuals with a high level of job satisfaction are more likely
      to engage in UPB through belongingness when corporate ethical values are low.
      Finally, the theoretical and managerial implications of these results are
      discussed.

PMID- 30238510
TI  - Clinical use of dimethyl fumarate in moderate-to-severe plaque-type psoriasis: a
      European expert consensus.
AB  - Fumaric acid esters (FAEs) are a group of small molecules that were first
      investigated for the treatment of psoriasis in 1959. The first fumarate-based
      drug - Fumaderm(r) - was approved in Germany in 1994 for severe psoriasis and
      then in 2008, the label was expanded to include moderate psoriasis. Fumaderm is a
      combination of different FAEs: dimethyl fumarate (DMF), which is regarded as the
      main active component, plus calcium, magnesium and zinc salts of monoethyl
      fumarate (MEF). FAEs are the most frequently used first-line systemic psoriasis
      treatment in Germany, with an overall treatment experience comprising more than
      220 000 patient-years. FAEs have demonstrated good, sustained clinical efficacy
      with an acceptable safety profile for the long-term treatment of patients with
      moderate-to-severe psoriasis. Indeed, the European S3-Guideline on the systemic
      treatment of Psoriasis vulgaris recommends FAEs for induction and long-term
      treatment. Until recently, FAEs were only licensed (for the psoriasis indication)
      in Germany, but were imported to many other European countries, such as The
      Netherlands, UK, Ireland, Austria and Italy, for the treatment of psoriasis. In
      2017, the European Medicines Agency (EMA) approved Skilarence(r) , a new oral
      formulation of DMF, for the treatment of adult patients with moderate-to-severe
      chronic plaque psoriasis in need of systemic therapy. Skilarence only contains
      DMF and is the first FAE for the treatment of psoriasis that has been approved by
      the EMA. This approval has given rise to a new oral treatment option for patients
      with moderate-to-severe plaque psoriasis across Europe. Here, we report the
      results of an expert meeting which was convened to deliver clinician-agreed
      consensus and real-world guidance on the clinical use of DMF in moderate-to
      severe chronic plaque psoriasis. Guidance on appropriate patient selection, DMF
      dosage considerations, monitoring and side-effect management is offered based
      upon available evidence and collective real-world clinical experience.

PMID- 30238511
TI  - Gold Decoration and Photoresistive Response to Nitrogen Dioxide of WS2 Nanotubes.
AB  - Composites of WS2 nanotubes (NT-WS2 ) and gold nanoparticles (AuNPs) were
      prepared using aqueous HAuCl4 solutions and subjected to surface analysis. The
      obtained materials were jointly characterized by X-ray photoelectron (XPS), Raman
      scattering (RSS), and ultraviolet photoelectron (UPS) spectroscopies. Optical
      extinction spectroscopy and electron energy loss spectroscopy in the scanning
      transmission electron microscopy regime (STEM-EELS) were also employed to study
      plasmon features of the nanocomposite. It was found that AuNPs deposition is
      accompanied by a partial oxidative dissolution of WS2 , whereas Au-S interfacial
      species could be responsible for the tight contact of metal nanoparticles and the
      disulfide. A remarkable sensitivity of n-type resistance of NT-WS2 and Au-NT-WS2
      to the adsorption of NO2 gas was also demonstrated at room temperature using
      periodical illumination by a 530 nm light-emitting diode. Au-NT-WS2
      nanocomposites are found to possess a higher photoresponse and enhanced
      sensitivity in the 0.25-2.0 ppm range of NO2 concentration, as compared to the
      pristine NT-WS2 . This behaviour is discussed within the physisorption-charge
      transfer model to explore sensing properties of the nanocomposites.

PMID- 30238512
TI  - A Simple and Fast Electrochemical CO2 Sensor Based on Li7 La3 Zr2 O12 for
      Environmental Monitoring.
AB  - In the goal of a sustainable energy future, either the energy efficiency of
      renewable energy sources is increased, day-to-day energy consumption by smart
      electronic feedback loops is managed in a more efficient way, or contribution to
      atmospheric CO2 is reduced. By defining a next generation of fast-response
      electrochemical CO2 sensors and materials, one can contribute to local monitoring
      of CO2 flows from industrial plants and processes, for energy management and
      building control or to track climate alterations. Electrochemical Li+ -garnet
      based sensors with Li7 La3 Zr2 O12 solid electrolytes can reach notable 1 min
      response time at lowered operation temperatures to track 400-4000 ppm levels of
      CO2 when compared with state-of-the-art NASICON-based sensors. By using
      principles of redefining the electrode electrochemistry, it is demonstrated that
      Li6.75 La3 Zr1.75 Ta0.25 O12 can be used to alter its classic use as energy
      storage function to gain additional functions such as CO2 tracking.

PMID- 30238513
TI  - Simple risk assessment in prostate cancer patients treated with primary androgen
      deprivation therapy: The Korean Cancer Study of the Prostate risk classification.
AB  - OBJECTIVES: To investigate the progression to castration-resistant prostate
      cancer after primary androgen deprivation therapy, and to build a simple risk
      prediction model for primary androgen deprivation therapy patients based on the
      Japan Cancer of the Prostate Risk Assessment criteria. METHODS: A total of 602
      patients who received primary androgen deprivation therapy were entered into the
      Korean Cancer Study of the Prostate database. The effect of prognostic factors
      was determined by multivariate analysis. For each patient, the weight of all
      factors was totaled to give Korean Cancer Study-prostate scores; patients were
      divided into three risk groups according to their score. The probability of
      castration-resistant prostate cancer, cancer-specific survival and overall
      survival was estimated by Kaplan-Meier analysis. RESULTS: On multivariate
      analysis for castration-resistant prostate cancer, the significant variables were
      initial prostate-specific antigen (>40 ng/mL; 1 point), biopsy Gleason score
      (>=9; 1 point), clinical N1 (1 point), and non-regional lymph node (1 point),
      bone (1 point) and visceral (1 point) metastasis. The Korean Cancer Study
      prostate scoring model was calculated on a scale of 0-6 (0: low, 1-2:
      intermediate, >=3: high risk). The risk groups stratified castration-resistant
      prostate cancer (P < 0.0001), cancer-specific survival (P < 0.0001) and overall
      survival (P < 0.0001) by Kaplan-Meier curve. The Korean Cancer Study-prostate
      model predicted castration-resistant prostate cancer with a c-index of 0.7242,
      cancer-specific survival with a c-index of 0.7036 and overall survival with a c
      index of 0.5890. The 5-year estimated castration-resistant prostate cancer/cancer
      specific death rates were 10.3%/6.3% in the low-risk group, 48.4%/22.2% in the
      intermediate-risk group and 81.7%/53.1% in the high-risk group. CONCLUSIONS: The
      Korean Cancer Study-prostate risk classification, a modified Japan Cancer of the
      Prostate Risk Assessment model, is a simple scoring model for predicting
      oncological outcomes after primary androgen deprivation therapy.

PMID- 30238514
TI  - Analysis of osseointegration of implants with hydrophilic surfaces in grafted
      areas: A Preclinical study.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of a hydrophilic
      surface on the osseointegration in grafted areas with deproteinized bovine bone
      (DBB) and with biphasic ceramics of hydroxyapatite/beta-tricalcium phosphate
      (HA/TCP). MATERIAL AND METHODS: Fifty-six rats were randomly allocated to four
      groups with 14 animals each: DBB: DBB+Machined surface; HA/TCP: HA/TCP+Machined
      surface; DBB-H: DBB+Hydrophilic surface; HA/TCP-H: HA/TCP+Hydrophilic surface.
      The bone defects were performed at the proximal epiphysis of the tibia. Then, the
      defects were filled with the biomaterials. After 60 days, the implants were
      placed in the grafted areas. The animals were submitted to euthanasia at periods
      of 15 and 45 days after the implants' placement. The osseointegration was
      assessed by biomechanical, microtomographic, and histometric analyses. In
      addition, the expression of bone morphogenetic protein-2 (BMP-2), alkaline
      phosphatase (ALP), and osteocalcin (OCN) was evaluated by immunohistochemistry.
      RESULTS: The HA/TCP-H group presented higher removal torque values and more
      mineralized tissue in the vicinity of the implants compared with the HA/TCP
      group. The DBB-H and HA/TCP-H groups presented higher values of bone-implant
      contact (at 15 and 45 days), of bone between the threads (45 days), and
      expression of BMP-2 (45 days) than the DBB and HA/TCP groups. Furthermore, the
      DBB-H group presented a higher expression of ALP than the DBB group (15 days).
      CONCLUSION: In conclusion, implants with a hydrophilic surface improve
      osseointegration in grafted areas compared to implants with machined surfaces in
      a rat tibia model.

PMID- 30238515
TI  - Use of some nutritional supplements in drinking water of growing turkeys during
      1st month of age and their effect on performance, meat quality, blood profile and
      antioxidant status.
AB  - The management practices implemented by the poultry sector as using some
      nutritional additives in the early stage of a bird's life can potentially detect
      other challenges to production development in the poultry farms. Many potential
      supplements can be included in the early feeding as which are added to drinking
      water. In this study, 180 1-day-old chicks were randomly distributed into six
      groups to investigate the use of some nutritional supplements in drinking water
      of growing turkeys during 1st month of age and their effect on growth
      performance, carcass traits, meat quality, leg problems, blood profile and
      oxidative status. Birds that were supplied with tap water were considered the
      control group (C), whereas the birds that received the 1st, 2nd, 3rd, 4th and 5th
      treatments (T1, T2, T3, T4 and T5, respectively) were supplied with drinking
      water containing 10% sugar syrup, molasses, lemon juice, skim milk and fresh egg
      albumin respectively. The different water additives significantly (p < 0.05)
      affected the body weight (BW) and body weight gain (BWG) at all studied ages
      except for the BW at 4 weeks old and BWG at 0-4 weeks old and 8-12 weeks old.
      Significant effects of the treatments on the feed consumption (FC) and feed
      conversion ratio (FCR) were not observed during the experiment, and the
      treatments did not cause significant differences (p < 0.05) in the carcass cut-up
      traits, bone measurements, body temperature, plumage conditions, mortality rates
      and blood parameters except for IgA (p = 0.043). The activity of superoxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px) was improved in the treatment
      groups with 10% molasses and lemon juice respectively. The total antioxidant
      capacity (T-AOC) and catalase (CAT) activities were enhanced in the treatments
      compared with the control group. The plasma malondialdehyde (MDA) levels were
      decreased with the sugar syrup, molasses and lemon juice treatments compared with
      those in the control and other groups. Supplementation of molasses or lemon juice
      to drinking water of turkeys during the 1st month of age resulted in a higher
      profit margin in comparison with the control group. The results showed that birds
      supplied with water containing 10% molasses or lemon juice during the growing
      period presented an improved growth performance, immune response, antioxidant
      status and economic efficiency.

PMID- 30238517
TI  - Early histological, microbiological, radiological, and clinical response to
      cemented and screw-retained all-ceramic single crowns.
AB  - OBJECTIVES: To assess the early histological, microbiological, radiological, and
      clinical response to cemented and screw-retained all-ceramic single-tooth implant
      supported reconstructions. MATERIALS AND METHODS: Patients with single-tooth
      implants were randomly allocated to receive a cemented lithium disilicate crown
      on a customized zirconia abutment (CEM) or a screw-retained crown with a directly
      veneered zirconia abutment (SCREW). At the screening visit, at crown insertion
      and at the 6-month follow-up, clinical parameters were measured at the implant
      and the contralateral tooth. Marginal bone levels, technical parameters, and
      esthetic outcomes were measured at the implants. At the 6-month follow-up, a
      microbiological test was performed and a soft tissue biopsy was harvested at the
      implants for histological analysis. Inflammatory cells and fibroblasts/-cytes
      were analyzed at the level of the sulcular epithelium, junctional epithelium, and
      connective tissue. The histological parameters were analyzed by means of a linear
      mixed model. RESULTS: Thirty-three patients completed the study, and implant and
      crown survival rates were 100% at 6 months. Histologically, the number of
      inflammatory cells tended to be higher in group CEM (p > 0.05). Moreover,
      significantly less inflammatory cells and fibroblasts/-cytes were found in the
      sulcular epithelium compared to the junctional epithelium and supracrestal
      connective tissue (p < 0.001). Four patients were tested positive for periodontal
      marker pathogens at the 6-month follow-up, and three of them belonged to group
      CEM. From crown insertion to the 6-month follow-up, median marginal bone levels
      changed only minimally and measured 0.31 and 0.32 mm in group CEM and 0.47 and
      0.36 mm in group SCREW, respectively. Clinical and esthetic parameters remained
      stable over time and were comparable between natural teeth and implants as well
      as between the groups. CONCLUSIONS: Cemented reconstructions were associated with
      more inflammatory cells, and more patients were diagnosed with periodonto
      pathogens. Both types of reconstructions resulted in similar radiological
      (marginal bone levels) and clinical outcomes (bleeding on probing and probing
      depth).

PMID- 30238516
TI  - State-of-the-art imaging techniques in the management of preoperative staging and
      re-staging of prostate cancer.
AB  - We aimed to review the current state-of-the-art imaging methods used for primary
      and secondary staging of prostate cancer, mainly focusing on multiparametric
      magnetic resonance imaging and positron-emission tomography/computed tomography
      with new radiotracers. An expert panel of urologists, radiologists and nuclear
      medicine physicians with wide experience in prostate cancer led a PubMed/MEDLINE
      search for prospective, retrospective original research, systematic review, meta
      analyses and clinical guidelines for local and systemic staging of the primary
      tumor and recurrence disease after treatment. Despite magnetic resonance imaging
      having low sensitivity for microscopic extracapsular extension, it is now a
      mainstay of prostate cancer diagnosis and local staging, and is becoming a
      crucial tool in treatment planning. Cross-sectional imaging for nodal staging,
      such as computed tomography and magnetic resonance imaging, is clinically useless
      even in high-risk patients, but is still suggested by current clinical
      guidelines. Positron-emission tomography/computed tomography with newer tracers
      has some advantage over conventional images, but is not cost-effective. Bone scan
      and computed tomography are often useless in early biochemical relapse, when
      salvage treatments are potentially curative. New imaging modalities, such as
      prostate-specific membrane antigen positron-emission tomography/computed
      tomography and whole-body magnetic resonance imaging, are showing promising
      results for early local and systemic detection. Newer imaging techniques, such as
      multiparametric magnetic resonance imaging, whole-body magnetic resonance imaging
      and positron-emission tomography/computed tomography with prostate-specific
      membrane antigen, have the potential to fill the historical limitations of
      conventional imaging methods in some clinical situations of primary and secondary
      staging of prostate cancer.

PMID- 30238518
TI  - Brainstem astroblastoma with MN1 translocation.
AB  - Astroblastoma is a rare glial neoplasm that occurs mostly in the cerebral
      hemisphere of children, adolescents and young adults. Although astroblastic
      perivascular pseudorosettes are unique histopathology of this neoplasm, diagnosis
      is usually challenging. Recently, it was discovered that the meningioma 1 gene
      (MN1)-altered pediatric central nervous system high-grade neuroepithelial tumors
      are actually astroblastomas. This case report presents a rare brainstem
      astroblastoma, with an unusual immunoprofile: negative for glial fibrillary
      acidic protein and oligodendrocyte transcription factor 2, but with a robust
      expression of pancytokeratin and epithelial membrane antigen. The diagnosis was
      confirmed based on the detection of MN1 rearrangement in a fluorescence in situ
      hybridization study, in addition to typical histopathology. Here we discuss the
      diagnostic pitfalls and unclear grading system along with a literature review.

PMID- 30238519
TI  - Intestinal microbiota profiling and predicted metabolic dysregulation in
      psoriasis patients.
AB  - OBJECTIVES: The intestinal microbiota has been known to involve in obesity and
      host immune response. We aimed to investigate the intestinal microbiota and
      potential genetic function in relation to clinical presentation in psoriasis
      patients. METHODS: Faecal microbiota and predicted genetic function inferred from
      high-throughput 16S ribosomal RNA sequencing were analysed between psoriasis (n =
      32) and age-, gender- and body mass index (BMI)-matched non-psoriasis subjects (n
      = 64), from a referral medical centre. The correlation between altered microbiota
      and disease activity, arthritis and systemic anti-psoriatic drugs was also
      investigated. RESULTS: We observed a distinct faecal microbial community
      structure in psoriasis patients, with an increased abundance of phylum Firmicutes
      and decreased abundance of phylum Bacteroidetes, across different subgroup of
      subjects. Ruminococcus and Megasphaera, of the phylum Firmicutes, were the top
      two genera of discriminant abundance in psoriasis. A number of functional genes
      and metabolic pathways involving bacterial chemotaxis and carbohydrate transport
      were predicted over-represented, whereas genes related to cobalamin and iron
      transport were predicted under-represented in faecal microbiota of psoriasis
      patients. CONCLUSIONS: The distinct faecal microbial composition in psoriasis
      might be associated with altered transport of carbohydrate, cobalamin and iron,
      as well as chemotaxis.

PMID- 30238520
TI  - Synthesis strategies and structural arrangements of isoreticular mixed-component
      metal-organic frameworks.
AB  - In recent years, the synthesis of mixed-metal and mixed-linker metal-organic
      frameworks with multiple metals and/or linker molecules combined in one framework
      has become a growing field of interest. These mixed-component or multivariate
      metal-organic framework materials provide the possibility to introduce multiple
      functionalities inside one framework. The interaction of guest molecules with
      different functionalities in the same material is a promising approach in the
      fields of gas storage, separation, catalysis and drug delivery. Furthermore, the
      combination of different components may lead to synergistic effects that cannot
      be achieved otherwise. These mixed-component approaches open up new pathways to
      an even larger range of possible customizations in the field of metal-organic
      frameworks.

PMID- 30238521
TI  - The Visible Light Challenge in Contemporary Photochemistry.
AB  - Catalyst-free and bond forming light induced reactions have seen an unprecedented
      renaissance in the realm of soft matter materials science due to their
      efficiency, spatio-temporal controllability and, sometimes, photoreversible
      nature. However, many of these reactions rely on the application of high energy
      UV light that can cause photo-degradation and is inapplicable in biological
      environments. If up-conversion systems or two photon processes are to be avoided,
      strategies for red-shifting catalyst-free ligation technology are critically
      required. This concept article introduces the reader to recent methods that lead
      to efficient, catalyst-free visible light induced ligation chemistry based on
      polyaromatic substituted photoreactive compounds - pyrene and anthracene - and
      furthermore emphasizes the broad and facile applicability of these molecules in
      polymeric material design. Concomitantly, we highlight that a careful action plot
      analysis of photochemical reactivity can provide deep insights into reactivity
      patterns, far beyond those suggested by the absorption spectrum. Indeed, we
      suggest that an action plot analysis is necessary for the evaluation any
      photochemical system and its response to structural chemical changes.

PMID- 30238522
TI  - Trends in Cancer Antigen 125 testing 2003-2014: A primary care population-based
      cohort study using laboratory data.
AB  - To understand Cancer Antigen 125 (CA125) testing in primary care in relation to a
      national guideline, we conducted a retrospective observational study including
      CA125 data from a well-defined region in the UK, from 2003 to 2014. 51,033 CA125
      tests from 30,737 women were stratified by month and year of testing, location of
      test request and patient age. Absolute numbers and rates of testing, rates and
      proportions of positive and negative tests, and frequencies of single and repeat
      tests were calculated. Negative binomial and logistic regression were used to
      test the effect of the guideline's introduction. Primary care testing spiked in
      the three months following the release of the guideline. However, there was no
      difference in the increase in testing observed across age groups. The proportion
      of positive tests decreased over time despite both the rates of positive and
      negative tests increasing. Retesting and repeat testing were associated with the
      initial CA125 value with no significant difference between women whose first test
      was 30-35 and >35 IU/L. Large studies using linked data are required to
      investigate the impact of increasing CA125 testing on onward intervention and
      patient outcomes. CA125 guidelines should be refined to avoid over-investigation
      in low risk age-groups.

PMID- 30238523
TI  - Effect of beta-glucan supplementation on feed intake, digestibility of nutrients
      and ruminal fermentation in Thai native beef cattle.
AB  - This study was conducted to evaluate the effect of beta-glucan on feed intake,
      digestibility of nutrients and ruminal fermentation in Thai native beef cattle
      that were fed low-quality roughage. Four, Thai native beef cattle with initial
      body weight (BW) of 100 +/- 20.0 kg were randomly assigned according to a 4 * 4
      Latin square design to receive four treatment by beta-glucan at 0, 1.6, 3.1 and
      4.7 g/day respectively. Supplementation of beta-glucan at 0-4.7 g in cattle did
      not affect the intake of DM, OM, CP, NDF or ADF. However, supplementation with
      beta-glucan significantly improved rice straw intake (g/kg BW0.75 ), compared to
      the nonsupplemented group (p < 0.05), so rice straw intake was higher than in the
      group without beta-glucan supplementation. In addition, total feed intake
      increased with the higher level of beta-glucan supplementation. The estimated
      energy intake was not altered by beta-glucan supplementation (p > 0.05). The
      experimental diet had no effect (p > 0.05) on the apparent digestibility of DM,
      OM, NDF or ADF. However, the digestibility of CP was significantly different
      among treatment and supplementation at 4.7 g/day beta-glucan which was the
      highest level (63.2%) among all diets. beta-glucan supplementation did not affect
      rumen pH, temperature or ruminal NH3 -N concentration. In addition, blood urea-N
      levels were similar among experimental groups. The population of protozoa at 4 hr
      post-feeding increased along with beta-glucan supplementation and was highest at
      4.7 g of beta-glucan. Based on this experiment, it could be concluded that
      supplementation of beta-glucan at 4.7 g improved rice straw intake, as well as
      total intake and digestibility of CP in Thai native beef cattle.

PMID- 30238524
TI  - Structural Effects of Fusicoccin upon Upregulation of 14-3-3-Phospholigand
      Interaction and Cytotoxic Activity.
AB  - Fusicoccins (FCs) exhibit various cellular activities in mammalian cells, but
      details of the mechanism of action are not fully understood. In this study, we
      synthesized two pairs of model derivatives of FCs differing only in the presence
      and absence of a 12-hydroxyl group and evaluated their binding to a 14-3-3
      protein together with various mode 1 and mode 3 phosphopeptide ligands. Our
      results demonstrate that the 12-hydroxyl group hampers binding to 14-3-3 with
      mode 1 phospholigands, presumably due to steric repulsion with the i+2 residue.
      Furthermore, cell-based evaluations showed that only non-substituted FCs exhibit
      significant cytotoxicity and all 12-hydroxyl derivatives were inactive,
      demonstrating a clear correlation with their ability to form ternary complexes
      with 14-3-3 and a mode 1 ligand. These results suggest that binding to 14-3-3 and
      a partner protein(s) possessing a mode 1 sequence plays a role in the mechanism
      of action of 12-non-substituted FCs.

PMID- 30238525
TI  - Policy intervention for access to medicine: Does it work similarly for poor and
      non-poor?
AB  - Many federal states in India have recently taken steps to improve distribution
      and affordability of medicines across public hospitals for reducing high out-of
      pocket (OOP) expenditure. West Bengal has introduced a Public-Private Partnership
      (PPP) scheme, Fair Price Medicine Shops (FPMS) within government hospitals in
      2012, which offers high discounts on maximum retail price of the drugs. This
      model introduces the state as a facilitator, rather than provider or financer, of
      health care. This paper attempts to measure its impact on OOP expenditure (OOPE)
      of patients using propensity-score-matching technique on the data collected from
      primary survey among patients. The study finds that although for non-poor
      patients, the average OOPE has reduced significantly, the impact has been counter
      productive for the poor patients, hinting that PPP intervention seems to work
      only for relatively better-off people, as the best alternative for the poorest
      remains to be free provision of drugs from the government. The difference in
      outcome lay in the fact that the nature of control groups differed between poor
      and non-poor patients. Those poor patients who did not visit FPMS received most
      of the medicines free (hence OOPE nearly zero), while for the non-poor patients
      not visiting FPMS bought the drugs from outside retail shops.

PMID- 30238526
TI  - Corannulenes with Electron-Withdrawing Substituents - Synthetic Approaches and
      Resulting Structural and Electronic Properties.
AB  - Corannulene is a multifaceted polyaromatic compound. It has many interesting
      properties, for example a bowl-shaped molecular structure which in addition
      undergoes a dynamic inversion process. It gained a lot of attraction within the
      last decades. This is not only due to its structural, but also its electronic
      properties and finally its various potential applications in materials chemistry.
      Herein, we summarize on the synthetic approaches towards corannulene derivatives
      with electron-withdrawing substituents. This includes both, selective and
      unselective methods. Further, the electrochemical properties, i. e. the reduction
      potentials are analysed and compared. As a main conclusion, one can state, that
      the electron affinity depends roughly linearly on the number of substituents.
      Finally, the structural behaviour of the substituted buckybowls in the solid
      state are highlighted. This also allows a general statement about the influence
      of the electronic and steric nature of substituents on the molecular structures
      and the solid-state packing of the corannulene derivatives.

PMID- 30238527
TI  - Obesity does not significantly impact outcomes following simultaneous liver
      kidney transplantation: review of the UNOS database - a retrospective study.
AB  - Simultaneous liver kidney transplantation (SLK) is the only curative option for
      patients with combined end stage liver and kidney disease. With the global
      obesity epidemic, an increasing number of obese patients are in need of SLK.
      However, the impact of pre-transplant obesity on outcomes after SLK is unknown.
      An analysis of the United States OPTN registry (Oct 1987 - June 2016) identified
      7205 SLK transplants. Of these, 1677 patients were overweight/obese (OW, BMI 30
      39) and 183 were morbidly obese (MO, BMI >=40). 29% of patients had NASH in the
      MO group versus 16.4% and 4.7% in the OW and normal weight (NW) groups,
      respectively. The 1, 3 and 5 year overall patient survival, kidney and liver
      graft survivals were comparable between the three groups. Numerically higher
      rates of acute kidney rejection were reported in the MO group at 1 year [12.73%,
      8.59%, and 10.05% for MO, OW and NW, respectively (P = 0.22)]. Multivariate
      analysis identified diagnosis of hepatitis C, donor age, diabetes mellitus, and
      delayed kidney transplant function but not BMI as risk factors for poor patient
      and both liver and kidney graft survival. Based on these findings, obesity should
      not be a contraindication for SLK even for patients with BMIs >= 40.

PMID- 30238528
TI  - An Electron-Rich Calix[4]arene-Based Receptor with Unprecedented Binding Affinity
      for Nitric Oxide.
AB  - Calixarenes have found widespread application as building blocks for the design
      and synthesis of functional materials in host-guest chemistry. The ongoing desire
      to develop a detailed understanding of the nature of NO bonding to
      multichromophoric pi-stacked assemblies led us to develop an electron-rich
      methoxy derivative of calix[4]arene (3), which we show exists as a single
      conformer in solution at ambient temperature. Here, we examine the redox
      properties of this derivative, generate its cation radical (3+. ) using robust
      chemical oxidants, and determine the relative efficacy of its NO binding in
      comparison with model calixarenes. We find that 3/3+. is a remarkable receptor
      for NO+ /NO, with unprecedented binding efficacy. The availability of precise
      experimental structures of this calixarene derivative and its NO complex,
      obtained by X-ray crystallography, is critically important both for developing
      novel functional NO biosensors, and understanding the role of stacked aromatic
      donors in efficient NO binding, which may have relevance to biological NO
      transport.

PMID- 30238529
TI  - Effects of continuous positive airway pressure on neurocognitive and
      neuropsychiatric function in obstructive sleep apnea.
AB  - The aim of this study was to determine the neurocognitive and neuropsychiatric
      effects of continuous positive airway pressure treatment on patients with
      obstructive sleep apnea. This cross-sectional, prospective, observational study
      included 126 patients with sleep apnea. The following tests were performed: the
      Montreal Cognitive Assessment for the evaluation of cognitive impairment, the
      Beck Depression Inventory, and the State-Trait Anxiety Inventory, together with
      the Epworth Sleepiness Scale for the evaluation of neuropsychiatric symptoms and
      a person's general level of daytime sleepiness. The first measurement did not
      show neurocognitive impairment or a higher level of depressive and anxiety
      symptoms in 126 patients with obstructive sleep apnea in comparison to normative
      standards. After the 3-month treatment indicated for 43 patients with obstructive
      sleep apnea, we did not find any significant improvement in cognitive performance
      (p = .213). However, patients with sleep apnea with continuous positive airway
      pressure treatment did show significantly less daytime sleepiness, anxiety and
      depressive symptoms (all p < .001). In conclusion, short-term (3 months)
      treatment of patients with obstructive sleep apnea can substantially alleviate
      their daytime sleepiness, as well as depressive and anxiety symptoms.

PMID- 30238530
TI  - "We make a direct impact on people's lives": Youth empowerment in the context of
      a youth-led participatory budgeting project.
AB  - Participatory budgeting [PB] is a democratic process whereby community members
      determine how to spend governmental funds. Youth-led PB is relatively new,
      occurring in select U.S. cities. During youth-led PB, youth collect ideas,
      develop proposals, and advertise community improvement projects for which they,
      citywide, cast deciding votes. The study examined opportunities for the
      empowerment youth at each stage of a youth-led PB project. Data collection
      included individual interviews with 31 youths and adult stakeholders, 3 focus
      groups with youths, and 7 observations of meetings. The data were analyzed using
      consensual qualitative research methods. Findings align well with the
      psychological empowerment literature and demonstrate several opportunities for
      empowerment throughout the PB project, including feeling in charge of the
      process, understanding and allocating resources, and influencing positive
      community change. Findings also demonstrate potential barriers to empowerment,
      including understanding bureaucratic decision making, and influencing policy. PB
      is relevant to furthering our understanding of the empowerment of youth. The
      youths who participated in the present study expressed feelings of competence,
      purpose, and an ability to use the skills learned to engage fellow youths in the
      PB process. Additional empirical research is needed to examine the dimensions of
      empowerment at each stage of the PB process.

PMID- 30238531
TI  - Structural features of two major nucleolar organizer regions (NORs), Nor-B1 and
      Nor-B2, and chromosome-specific rRNA gene expression in wheat.
AB  - The reference genome sequence of wheat 'Chinese Spring' (CS) is now available
      (IWGSC RefSeq v1.0), but the core sequences defining the nucleolar organizer
      regions (NORs) have not been characterized. We estimated that the total copy
      number of the rDNA units in the wheat genome is 11 160, of which 30.5%, 60.9% and
      8.6% are located on Nor-B1 (1B), Nor-B2 (6B) and other NORs, respectively. The
      total length of the NORs is estimated to be 100 Mb, corresponding to
      approximately 10% of the unassembled portion of the genome not represented in
      RefSeq v1.0. Four subtypes (S1-S4) of the rDNA units were identified based on
      differences within the 3' external transcribed spacer regions in Nor-B1 and Nor
      B2, and quantitative PCR indicated locus-specific variation in rDNA subtype
      contents. Expression analyses of rDNA subtypes revealed that S1 was predominantly
      expressed and S2 weakly expressed, in contrast to the relative abundance of rDNA
      subtypes in the wheat genome. These results suggest a regulation mechanism of
      differential rDNA expression based on sequence differences. S3 expression
      increased in the ditelosomic lines Dt1BL and Dt6BL, suggesting that S3 is
      subjected to chromosome-mediated silencing. Structural differences were detected
      in the regions surrounding the NOR among homoeologous chromosomes of groups 1 and
      6. The adjacent regions distal to the major NORs were expanded compared with
      their homoeologous counterparts, and the gene density of these expanded regions
      was relatively low. We provide evidence that these regions are likely to be
      important for autoregulation of the associated major NORs as well as silencing of
      minor NORs.

PMID- 30238532
TI  - Conflict management styles of nurse managers working in inpatient institutions:
      the case of Turkey.
AB  - AIM: The present study aimed to determine conflict-resolution styles of nurse
      managers working in hospitals where organisational conflicts are common, and
      factors affecting their styles. BACKGROUND: When conflicts and/or administrative
      problems are encountered at different levels of nursing services, nurse managers'
      communication skills and approaches play a key role in problem solving. METHODS:
      This study was conducted in Sivas, a province in the eastern part of Turkey. The
      study sample involved 116 nurse managers working in inpatient institutions. Data
      were collected with the Sociodemographic Characteristics Questionnaire and the
      Rahim Organizational Conflict Inventory. RESULTS: Of the conflict-management
      styles, the one preferred by the participating nurse managers was collaborating,
      followed by compromising, avoiding, competing, and accommodating. However, age,
      educational background, length of service, and managerial experience were
      effective in determining the style of conflict resolution. CONCLUSION: It was
      concluded that nurse managers preferred the collaborating style to manage
      conflicts because it is a positive and effective conflict-management style, and
      that a variety of variables played a role in their decision to adopt this style.
      IMPLICATIONS FOR NURSING MANAGEMENT: Conflicts have an adverse effect on the
      productivity, morale, and patient care of all the health care team, which might
      lead to a rapid turnover of employees or dissatisfaction. Using conflict
      resolution strategies in the workplace will help maintain a healthy work
      environment.

PMID- 30238533
TI  - Intravoxel Incoherent Motion Diffusion-Weighted MRI of Invasive Breast Cancer:
      Correlation With Prognostic Factors and Kinetic Features Acquired With Computer
      Aided Diagnosis.
AB  - BACKGROUND: As both intravoxel incoherent motion (IVIM) modeling and dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) provide perfusion
      parameters, IVIM-derived perfusion parameters might be expected to correlate with
      the kinetic features from DCE-MRI. PURPOSE: To investigate the association
      between IVIM parameters and prognostic factors and to evaluate the correlation
      between IVIM parameters and kinetic features in invasive breast cancer patients
      using computer-aided diagnosis (CAD). STUDY TYPE: Retrospective. POPULATION:
      Eighty-five patients (invasive cancers; mean size, 1.8 cm; range, 0.8-4.8 cm) who
      underwent diffusion-weighted imaging with 12 b-values (0-1000 s/mm2 ). FIELD
      STRENGTH/SEQUENCE: 3.0T MRI axial, IVIM-DWI epi-sequence, and DCE-MRI.
      ASSESSMENT: Two radiologists measured the apparent diffusion coefficient (ADC),
      diffusion coefficient, pseudodiffusion coefficient, and perfusion fraction (f)
      using IVIM modeling. Kinetic features such as peak enhancement and early and
      delayed enhancement profiles were acquired using CAD. STATISTICAL TESTS: The
      correlation between the IVIM parameters and kinetic features and the association
      between the IVIM parameters and prognostic factors were investigated using Mann
      Whitney test and Spearman correlation test. RESULTS: There were no significant
      associations between IVIM parameters and prognostic factors. When IVIM parameters
      were correlated with kinetic features by CAD, both the ADC and f values showed
      correlations with delayed enhancement profiles. The ADC values were lower in
      tumors with lower persistent components (P = 0.013) and higher washout components
      (P = 0.045) and showed a positive correlation with persistent proportion
      (Spearman's rho (r) = 0.222, P = 0.041). The f value was higher in tumors with
      higher persistent components (P = 0.021) and showed a positive correlation with
      persistent proportion (r = 0.227, P = 0.029). DATA CONCLUSION: This analysis
      revealed that IVIM-derived ADC and f values showed correlations with kinetic
      features at the delayed phase as assessed by CAD. These results indicate the
      potential of IVIM imaging biomarkers to provide information on the biological and
      kinetic properties of breast cancers without a contrast agent. LEVEL OF EVIDENCE:
      4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30238534
TI  - Modulation of autophagy in the protective effect of resveratrol on PM2.5-induced
      pulmonary oxidative injury in mice.
AB  - Ambient fine particulate matter (PM2.5) is capable of inducing pulmonary
      oxidative injury. Autophagy maintains basal cellular homeostasis and plays a
      critical role in the pathogenesis of lung diseases. Resveratrol, a natural
      polyphenol, is an effective antioxidant agent against particulate matter (PM)
      induced injuries. The current study was designed to investigate whether
      resveratrol can regulate autophagy in the process of PM2.5-mediated pulmonary
      oxidative injury. In the mice model of PM2.5 exposure, we found that PM2.5
      increased the contents of malondialdehyde (MDA) and nitric oxide (NO) while
      decreased the expression of nuclear factor erythroid-2-related factor 2 in the
      lungs. The levels of 8-hydroxydeoxyguanosine and inflammatory cytokines were
      increased following PM2.5 exposure. Histological analysis of the lungs revealed
      inflammatory change in PM2.5 group. Meanwhile, PM2.5 triggered autophagy, as
      evidenced by the elevated expression of microtubule-associated proteins light
      chain 3II, Beclin1 and p62. Transmission electron microscopy images showed that
      autophagosomes accumulated in the lungs after PM2.5 exposure. Furthermore,
      resveratrol intervention suppressed autophagy and attenuated the oxidative injury
      resulting from PM2.5 exposure. Our findings provided a valuable insight into the
      underlying mechanism for the protective effects of resveratrol against PM2.5
      induced lung injury, which involves suppression of the autophagic process.

PMID- 30238535
TI  - Phyllanthin from Phyllanthus amarus inhibits LPS-induced proinflammatory
      responses in U937 macrophages via downregulation of NF-kappaB/MAPK/PI3K-Akt
      signaling pathways.
AB  - Phyllanthin, a lignan from Phyllanthus species, has been reported to possess
      potent immunosuppressive properties on immune cells and on adaptive and innate
      immune responses in animal models. Herein, we investigated the inhibitory effects
      of phyllanthin isolated from Phyllanthus amarus on nuclear factor-kappa B (NF
      kappaB), mitogen-activated protein kinase (MAPK), and PI3K-Akt signal transducing
      pathways in LPS-activated U937 cells. The lipopolysaccharide-stimulated excess
      production of prostaglandin was significantly suppressed by phyllanthin via the
      mechanisms linked to the modulatory effects of cyclooxygenase 2 protein and gene
      expression. Phyllanthin also significantly inhibited the release and mRNA
      expression of proinflammatory cytokines (interleukin-1 beta and tumor necrosis
      factor-alpha). Phyllanthin also significantly downregulated the phosphorylation
      of IkappaBalpha, NF-kappaB (p65), and IKKalpha/beta and suppressed the activation
      of JNK, ERK, p38MAPK, and Akt in a concentration-dependent manner. Additionally,
      phyllanthin downregulated the expression of upstream signaling molecules
      including MyD88 and toll-like receptor 4 that are essential for the activation of
      NF-kappaB, MAPKs, and PI3K-Akt signal transducing pathways. Based on these
      observations, phyllanthin may exert their suppressive effects on inflammatory
      process by mediating the release of inflammatory signaling molecules via the NF
      kappaB, MAPKs, and PI3K-Akt signal transducing pathways. Thus, phyllanthin holds
      a great promise as a potential anti-inflammatory agent to treat various
      inflammatory diseases.

PMID- 30238536
TI  - Immune receptor genes and pericentromeric transposons as targets of common
      epigenetic regulatory elements.
AB  - Pattern recognition receptors (PRR) and nucleotide-binding leucine-rich repeat
      proteins (NLR) are major components of the plant immune system responsible for
      pathogen detection. To date, the transcriptional regulation of PRR/NLR genes is
      poorly understood. Some PRR/NLR genes are affected by epigenetic changes of
      neighboring transposable elements (TEs) (cis regulation). We analyzed whether
      these genes can also respond to changes in the epigenetic marks of distal
      pericentromeric TEs (trans regulation). We found that Arabidopsis tissues
      infected with Pseudomonas syringae pv. tomato (Pst) initially induced the
      expression of pericentromeric TEs, and then repressed it by RNA-directed DNA
      methylation (RdDM). The latter response was accompanied by the accumulation of
      small RNAs (sRNAs) mapping to the TEs. Curiously these sRNAs also mapped to
      distal PRR/NLR genes, which were controlled by RdDM but remained induced in the
      infected tissues. Then, we used non-infected mom1 (Morpheus' molecule 1) mutants
      that expressed pericentromeric TEs to test if they lose repression of PRR/NLR
      genes. mom1 plants activated several PRR/NLR genes that were unlinked to MOM1
      targeted TEs, and showed enhanced resistance to Pst. Remarkably, the increased
      defenses of mom1 were abolished when MOM1/RdDM-mediated pericentromeric TEs
      silencing was re-established. Therefore, common sRNAs could control PRR/NLR genes
      and distal pericentromeric TEs and preferentially silence TEs when they are
      activated.

PMID- 30238537
TI  - Cell block is a valuable adjunct to conventional smear for thyroid fine needle
      aspiration: 2395 cases with histological correlation.
AB  - AIMS: Conventional smears (CS) of samples obtained by fine needle aspiration
      (FNA) have proven useful in thyroid nodules evaluation, but the additional
      contribution of cell block (CB) has only been investigated in a limited fashion.
      In this study, we aimed to evaluate whether the auxiliary application of CB adds
      to the diagnostic accuracy of the CS by a College of American Pathologists
      accredited hospital laboratory. METHODS: All thyroid FNA samples processed with
      CS only or combined CB and CS in West China Hospital from January 2011 to
      December 2015 were retrospectively collected. All specimens were classified
      according to Bethesda System, and the distribution of Bethesda (2009) categories
      was compared between CS and combined CS and CB. Further, we compared the
      diagnostic performance between these two groups for nodules with follow-up
      histopathology. RESULTS: A total of 11 011 thyroid nodules from 10 206 patients
      were included. Of these, 2395 nodules from 2211 patients underwent surgical
      resection. The unsatisfactory rate decreased significantly from 18.1% to 9.8% in
      the total group and from 1.7% to 0.8% in the group with surgery after combined
      use of CS and CB. The proportion of atypia/follicular lesion of undetermined
      significance also declined slightly. Furthermore, all of the sensitivities,
      specificities, accuracies and positive predictive values increased significantly
      after the combined use of CS and CB for different calculation methods.
      CONCLUSIONS: Combined use of CS and CB can significantly decrease the
      unsatisfactory rate of thyroid FNAs, improve the diagnostic efficacy, and thus
      should be routinely applied in thyroid nodule evaluation if available.

PMID- 30238538
TI  - Inspecting the Electronic Architecture and Semiconducting Properties of a Rosette
      Like Supramolecular Columnar Liquid Crystal.
AB  - Computational and experimental studies unravel the structural and electronic
      properties of a novel supramolecular liquid crystal built through a hierarchical
      assembly process resulting in an H-bonded melamine rosette decorated with
      peripheral triphenylenes. The six-fold symmetry of the mesogen facilitates the
      formation of a highly organized hexagonal columnar mesophase stable at room
      temperature. X-ray diffraction and electron density maps confirm additional intra
      and intercolumn segregation of functional subunits, and this paves the way for
      1D charge transport. Indeed, hole mobility has been measured and found to be
      higher than for related mesogens. DFT calculations of HOMO and LUMO levels and
      parameters such as reorganization energy and transfer integral of the rosette
      structure have been achieved, and not only validate the columnar organization but
      also establish the way it translates into a favorable electronic architecture and
      molecular orbital interactions to promote charge carrier mobility.

PMID- 30238539
TI  - Nursing networks in the NICU and their association with maternal stress: A pilot
      study.
AB  - AIMS: This pilot study explored how maternal stress experienced in the neonatal
      intensive care unit (NICU) is affected by the individual nursing structure and
      the network that provides care to extremely preterm infants. BACKGROUND: Mothers
      experience high stress when their extremely preterm infants are hospitalized in
      the NICU. This often translates into maladaptive parenting behaviours that
      negatively affect the long-term cognitive, social, and emotional development of
      the infant. Efforts to identify modifiable sources of maternal stress in the NICU
      could lead to improvement in maternal engagement and, ultimately, long-term
      neurodevelopmental outcomes. METHOD: Time- and date-stamped nursing shift data
      were extracted from the medical record and transformed into five structural
      nursing metrics with resultant nurse data networks. These were then analysed for
      associations with maternal stress outcomes on the Parental Stressor Scale (PSS:
      NICU). RESULTS: Infants experienced highly variable nursing care and networks of
      nurses throughout their hospitalization. This variability is associated with the
      PSS: NICU (a) Sights and Sounds and (b) Altered Parental Role subscales.
      CONCLUSION: Nursing structure and the resultant caregiving network have an impact
      on maternal stress. IMPLICATIONS FOR NURSING MANAGEMENT: Changing the pattern of
      nurse staffing may be a modifiable intervention target for reducing maternal
      stress in the NICU.

PMID- 30238540
TI  - Servo-controlled cooling during neonatal transport for babies with hypoxic
      ischaemic encephalopathy is practical and beneficial: Experience from a large UK
      neonatal transport service.
AB  - AIM: Servo-controlled therapeutic hypothermia is a routine therapy for babies
      with hypoxic-ischaemic encephalopathy in the neonatal unit and is delivered in
      designated cooling centres. It is increasingly being used during neonatal
      transport in the UK to deliver this therapy in a timelier manner for babies not
      born in a cooling centre. Prior to the implementation of this treatment, passive
      cooling alone was used in transport. Comparison of passive and servo-controlled
      cooling during neonatal transfers with reference to: (i) the proportion of babies
      in the therapeutic range (33-34 degrees C) at three time points during the
      transport mission (arrival of the team at the referring unit, departure of the
      team from the referring unit and at the completion of transport); (ii) the
      proportion of babies overcooled at any point once the transport team was present
      (<33 degrees C); and (iii) duration of phases of the transfer to evaluate the
      impact of active cooling on how long it takes to undertake transfer. METHODS:
      This was a retrospective observational study comparing babies with passive and
      servo-controlled hypothermia (January 2015 to May 2016) following introduction of
      the servo-controlled cooling mattress. RESULTS: A total of 48 patients were
      treated with hypothermia in transit (29 passive, 19 servo-controlled). The median
      gestational age (GA) was 40 weeks (interquartile range: 39-41) and mean
      birthweight (BW) 3420 g (standard deviation 600 g); there was no differences in
      GA, BW and clinical characteristics between the groups. There was a statistically
      significant difference in the temperature at the end of the transport, where 94%
      (n = 18) of babies who received servo-controlled cooling were in the target
      temperature in comparison with only 65% (n = 19) of the passive cooling group
      babies (P = 0.045). In addition, none of the babies in the servo-controlled group
      were warm (>34 degrees C) at the end of the transfer. Babies who underwent servo
      controlled cooling are more likely to maintain a target temperature (33-34
      degrees C) (17 (89%) vs. 17 (58%), P = 0.021); in particular, there is less
      overcooling (<33 degrees C) in this group (2 (10%) vs. 15 (51%), P = 0.004).
      Total mission time was not significantly different. CONCLUSION: The use of servo
      controlled cooling devices during neonatal transport improves the ability to
      maintain the baby's temperature within the target range (33-34 degrees C) with
      less overcooling.

PMID- 30238541
TI  - Factors influencing nurses' willingness to lead.
AB  - AIM: To identify factors influencing nurses' willingness to lead. BACKGROUND:
      Given the ageing workforce and the projected retirement of nurse leaders, there
      is a concern about nursing leadership shortages in the next decade. Several
      studies have shown that nurses are not interested in pursuing leadership
      positions, but studies investigating nurses' willingness to lead and related
      predictors remain limited. METHODS: A workforce survey of 1,201 direct-care
      nurses was conducted in Oregon. Logistic regression modelling was used to
      identify factors influencing the likelihood of nurses' willingness to lead.
      RESULTS: Fifty-three percent of nurses were willing to pursue leadership roles.
      Years of experience, job burnout, the perception of the work environment,
      adequacy of leadership preparation, and the amount of salary and compensation
      were significant predictors of nurses' willingness to lead. CONCLUSION:
      Increasing nurses' participation in hospital affairs and providing adequate
      leadership preparation, parts of the work environment, prior to engaging them in
      leadership roles is recommended to improve their attitudes about leading.
      IMPLICATIONS FOR NURSING MANAGEMENT: Recruitment of future nursing leaders should
      not be based solely on demographics such as age and gender. Rather, recruiters
      should focus on creating more favourable work environments in which to lead.

PMID- 30238542
TI  - Hospitalisations and emergency department visits in cancer patients receiving
      systemic therapy: Systematic review and meta-analysis.
AB  - Emergency department visits and hospitalisations (ED+H) during systemic therapy
      are undesirable for both patients and the health system. We undertook a
      systematic literature review and meta-analysis to evaluate the frequency of
      unplanned all-cause and treatment-related ED+H among adults receiving adjuvant or
      palliative-intent systemic therapy for all cancers. Randomised controlled trials
      (RCT) and observational studies (OS) reporting ED+H were identified from Medline
      and EMBASE from inception to June 2016. Quality was assessed using modified
      STROBE, CONSORT or PRISMA guidelines, depending on study type. A total of 112 OS
      (308,662 patients) and 26 RCTs (16,081 patients) met inclusion criteria. Most
      articles focused on palliative treatment (59%) delivered as first-line, in
      breast, lung and colorectal cancers. Only 20 articles reported ED frequency.
      Treatment-related and all-cause hospitalisations were more common in routine
      practice than in RCTs (29% vs. 16% and 42% vs. 28% respectively); frequency
      varied by treatment intent and tumour site. Methodological issues were common,
      particularly poor definition of the at-risk period. Hospitalisations are common,
      especially in unselected populations, but few articles report this and do so
      poorly. Routine, standardised reporting of ED+H during chemotherapy should be
      included in RCT reports and evaluated in routine care following adoption of new
      treatments.

PMID- 30238543
TI  - EhRab21 mobilization during erythrophagocytosis in Entamoeba histolytica.
AB  - Rab proteins are present in all eukaryotic lineages and regulate vesicular
      trafficking. Entamoeba histolytica has approximately 100 genes encoding Rab
      proteins, among which 16 have homology with human Rab proteins. Human Rab21
      participates in integrin recycling, and thus amoebic Rab21 was believed to
      regulate the mobilization of Ehbeta1FNR (integrin-like fibronectin receptor
      related with human integrin beta1). We analyzed the distribution of EhRab21 using
      a polyclonal antibody produced with a specific peptide against the amoebic Rab
      protein, using confocal microscopy and specific probes for different organelles.
      EhRab21 was not associated with Ehbeta1FNR in fibronectin-stimulated
      trophozoites. However, EhRab21 was relocalized to lysosomes in
      erythrophagocytosis assays and was also found in Golgi-positive structures and
      the nuclear periphery. These results suggest that EhRab21, unlike its human
      homologue, is not present in the recycling pathway. However, according to the
      results, EhRab21 may regulate the trafficking between lysosomes and the Golgi
      apparatus.

PMID- 30238544
TI  - Design of Hollow Nanostructures for Energy Storage, Conversion and Production.
AB  - Hollow nanostructures have shown great promise for energy storage, conversion,
      and production technologies. Significant efforts have been devoted to the design
      and synthesis of hollow nanostructures with diverse compositional and geometric
      characteristics in the past decade. However, the correlation between their
      structure and energy-related performance has not been reviewed thoroughly in the
      literature. Here, some representative examples of designing hollow nanostructure
      to effectively solve the problems of energy-related technologies are highlighted,
      such as lithium-ion batteries, lithium-metal anodes, lithium-sulfur batteries,
      supercapacitors, dye-sensitized solar cells, electrocatalysis, and
      photoelectrochemical cells. The great effect of structure engineering on the
      performance is discussed in depth, which will benefit the better design of hollow
      nanostructures to fulfill the requirements of specific applications and
      simultaneously enrich the diversity of the hollow nanostructure family. Finally,
      future directions of hollow nanostructure design to solve emerging challenges and
      further improve the performance of energy-related technologies are also provided.

PMID- 30238545
TI  - "Creating a family after battling cancer is exhausting and maddening": Exploring
      real-world experiences of young adult cancer survivors seeking financial
      assistance for family building after treatment.
AB  - OBJECTIVE: Young adult (YA) cancer survivors who received gonadotoxic therapy are
      at risk for impaired fertility and/or childbearing difficulties. This study
      explored the experiences and financial concerns of survivors pursuing family
      building through assisted reproductive technology (ART) and adoption. METHODS:
      Retrospective study of data collected from grant applications for financial
      assistance with family building. Grounded theory methodology using an inductive
      data-driven approach guided qualitative data analysis. RESULTS: Participants (N =
      46) averaged 32 years old (SD = 3.4) were primarily female (81%) and
      married/partnered (83%). Four main themes were identified representing the (1)
      emotional experiences and (2) financial barriers to family building after cancer,
      (3) perceived impact on partners, and (4) disrupted life trajectory. Negative
      emotions were pervasive but were balanced with hope and optimism that parenthood
      would be achieved. Still, the combination of high ART/adoption costs, the
      financial impact of cancer, and limited sources for support caused extreme
      financial stress. Further, in the face of these high costs, many survivors
      reported worry and guilt about burdening partners, particularly as couples failed
      to meet personal and societal expectations for parenthood timelines. CONCLUSION:
      After cancer, YAs face numerous psychosocial and financial difficulties in their
      pursuits of family building when ART/adoption is needed to achieve parenthood.
      Survivors interested in future children may benefit from follow-up fertility
      counseling post-treatment including discussion of ART options, surrogacy, and
      adoption, as appropriate, and potential barriers. Planning for the financial cost
      and burden in particular may help to avoid or mitigate financial stress later on.

PMID- 30238546
TI  - A pilot study evaluating depression in mothers with children diagnosed with Down
      syndrome in state health care.
AB  - BACKGROUND: Parenting a child who has an intellectual disability has been shown
      to increase the risk for developing depression. The purpose of this study was to
      screen for depression and to determine if there is an association between
      depressive symptoms and certain sociodemographic factors in mothers with a child
      diagnosed with Down syndrome in state health care facilities in Johannesburg.
      METHODS: The study included 30 biological mothers of children between 6 months
      and 3 years diagnosed with Down syndrome postnatally. The Edinburgh Postnatal
      Depression Scale (EPDS) was used to assess depression in participants. A 10-item
      sociodemographic questionnaire was concurrently administered. Data analysis was
      conducted using descriptive and inferential statistical analysis. RESULTS: The 30
      mothers had a mean EPDS score of 9.1 (SD = 5.89) with scores ranging between 0
      and 26. Eight mothers (26.7%) screened positive for depression with an EPDS score
      of 13 or greater. A statistically significant association was found between an
      HIV-positive status and mothers who had an EPDS score of 13 or greater (P =
      0.01). No significant association between depression and various other
      sociodemographic factors was identified. CONCLUSIONS: Mothers with a child
      diagnosed with Down syndrome may be vulnerable to developing depression. A
      significant association was found between a positive HIV status and symptoms of
      depression, in mothers with a child diagnosed with Down syndrome. This study
      indicates the need for further investigations assessing the causes and risk
      factors resulting in postnatal depression in mothers with a child diagnosed with
      Down syndrome.

PMID- 30238547
TI  - Impact of sexually antagonistic genital morphologies on female reproduction and
      wild population demography.
AB  - Sexual conflict is a strong driver of evolution. The evolutionary outcomes of
      sexual conflict can, in turn, influence ecological processes within populations,
      for example, demography. However, evidence for the latter hypothesis is scarce,
      especially in the wild. Here, we show that sexual conflict is associated with
      demographic processes determining population size in the ground beetle Carabus
      insulicola with elaborate male and female genitalia based on individual- and
      population-level analyses. We found that sexually antagonistic selection can
      operate on the genitalia: longer male genitalia can be beneficial in sperm
      competition but decrease female reproductive success with increased egg dumping,
      whereas longer female genitalia are resistant to this male harassment via
      decreased egg dumping and increased fertilization rate. As expected from sexually
      antagonistic coevolution due to sexual conflict, we detected coevolutionary
      divergence between male and female genital sizes among populations. In parallel
      with decrease in female reproductive success, more harmful males with longer
      genitalia and less resistant females with shorter genitalia were related to small
      effective population sizes. Thus, sexual conflict may promote coevolutionary
      diversification between sexual traits, and this was associated with a demographic
      process. Our findings provide an insight into sex-driven eco-evolutionary
      dynamics in the wild.

PMID- 30238548
TI  - The configuration of DMD and the maximum intensity projection method for
      improving contrast in DMD-based confocal microscope.
AB  - In this article, an operation strategy of digital micromirror device (DMD) and
      the maximum intensity projection (MIP) image processing method are proposed to
      improve the contrast of images in confocal microscopy. First, the configuration
      of DMD is demonstrated and the effect of scanning unit size on image performance
      is analyzed. Then, the image processing method MIP is applied. According to the
      MIP method, only the maximum intensity projection point of the same pixel is
      chosen from every image, and the maximum intensity projection point exactly
      corresponds to the positon where mirror is at "on" position during the scanning
      process in DMD-based confocal microscope system,. Thus, high contrast of images
      can be achieved by using MIP. Finally, experiments are conducted to verify
      imaging performance by changing the parameter of scanning unit size and applying
      a MIP image processing technique. The results show that DMD scanning unit size
      and MIP image processing techniques play important roles in improving image
      contrast. Smaller scanning unit size of DMD improves axial contrast but greatly
      decreases the signal to noise ratio, which thus leads to reduced image contrast.
      Larger scanning unit size produces a better signal to noise ratio, thus better
      image contrast. However, a large S will sacrifice the processing time. Therefore,
      DMD scanning unit size should be smaller on the premise that image contrast can
      be satisfied. RESEARCH HIGHLIGHTS: Effect of DMD scanning unit size setting on
      image contrast is analyzed and verified. The maximum intensity projection (MIP)
      is investigated to improve the image contrast. Experiments are conducted to
      verify the enhancement of the image contrast.

PMID- 30238550
TI  - Refill Procedures of Intrathecal Drug Delivery Systems With a Recessed Fill Port
      on the Pump Surface: A Prospective Comparison Study of Ultrasound-Guided vs.
      Blind Refill Technique.
AB  - OBJECTIVES: Structural differences of implantable drug delivery systems (IDDSs)
      might have an impact on the efficiency of needle access to the reservoir fill
      port (RFP). The aim of this study was to assess the efficiency of RFP needle
      access with an ultrasound (US)-guided vs. a blind refill technique in IDDSs with
      a Recessed RFP (Recessed-RFP-IDDS). MATERIALS AND METHODS: The primary outcome
      was the number of attempts needed to enter the RFP with a needle comparing the US
      guided technique vs. the blind refill technique. The time to enter the RFP with
      the needle was a secondary outcome. We compared the amount of attempts between
      both techniques with the non-parametric Wilcoxon rank sum test. RESULTS: Fourteen
      adult patients underwent a total of 75 refills of their Recessed-RFP-IDDS during
      a period of 24 months. The median number of attempts to enter the RFP did not
      differ significantly between the US-guided technique and the blind refill
      technique (2.0 (IQR: 1-5) vs. 1.5 (IQR: 1-5.0), p = 0.572). The median time to
      enter the RFP with the needle did not differ significantly between both
      techniques (35.0 sec (IQR: 26.0-58.0) vs. 41.0 sec (IQR: 25.5-46.8), p = 0.878).
      CONCLUSION: The results of this study suggest that there is no difference in the
      RFP needle access efficiency between the US-guided and the blind refill technique
      in superficially located Recessed-RFP-IDDSs, if performed by experienced
      practitioners. However, the study did not address efficiency of the RFP needle
      access in IDDSs with aberrancy in pump location or refills performed by
      inexperienced staff.

PMID- 30238549
TI  - Sex influences diaphragm muscle response in exercised mdx mice.
AB  - Physical exercise promotes increased muscle damage in the mdx mice, the
      experimental model of Duchenne muscular dystrophy. Studies suggest that the
      estrogen level in females makes them less susceptible to muscle injuries. The aim
      of this study was to characterize the diaphragm (DIA) muscle response to physical
      exercise in male and female mdx mice. The animals were divided into four groups:
      female sedentary mdx; male sedentary mdx; female mdx submitted to exercise; and
      male mdx mice submitted to exercise. Blood samples were used to determine
      creatine kinase (CK). Regenerated muscle fibers were indicated by the presence of
      central nucleus and also inflammation areas were determined in DIA muscle
      sections. The alpha and beta estrogen receptors (ER) were determined by means of
      immunohistochemistry evaluation in the dystrophic DIA muscle. Male mdx animals
      submitted to exercise showed increased CK levels and inflammatory area. The
      quantification of regenerated fibers was higher in male animals, submitted or not
      to physical exercise. Greater alpha and beta ER expression was verified in the
      females submitted to exercise in the DIA muscle than in the other experimental
      groups. Therefore, estrogen may have contributed to the prevention of increased
      inflammatory process and DIA injury in females submitted to exercise.

PMID- 30238551
TI  - The influence of weather on avian spring migration phenology: What, where and
      when?
AB  - Over the past decades, spring arrival and passage of most short- and medium
      distance migrating birds in the Northern Hemisphere have advanced. Changes in
      spring temperature at the passage or arrival area have been most frequently shown
      to be related to these changes in spring migration phenology. In most studies,
      preliminary assumptions are made on both the spatial location and the specific
      time frame of the weather influencing spring migration phenology. We performed a
      spatially explicit time-window analysis of the effect of weather on mean spring
      passage dates of nine short- and medium-distance passerines. We analysed data
      from standardized daily captures at the Helgoland (Germany) constant-effort site,
      in combination with gridded daily temperature, precipitation and wind data from
      the NCEP data set over a 55-year period (1960-2014), across the whole of West
      Europe and North Africa. Although we allowed for a time window of any length at
      any location, nevertheless incorporating various measures to avoid spurious
      correlations, time windows at the likely wintering or spring stopover grounds
      were almost exclusively selected as the best predicting variables (96%-100% of
      identified variables). The weather variables at the wintering and stopover
      grounds explain up to 77% of the interannual variability in spring passage. Yet,
      the response of spring migration phenology to weather at the winter or stopover
      areas does not fully explain the observed trends. Spring migration phenology is,
      hence, strongly driven by weather at the wintering and stopover grounds, but
      additional mechanisms are needed to fully explain the advancement of spring
      migration. Our results also clearly show that previously illustrated
      correlations, or the lack thereof, between spring migration phenology and weather
      at the passage or arrival location are due to spatio-temporal correlations in the
      weather data. This spatial mismatch might have led to false conclusions,
      especially the further away the wintering or stopover sites are.

PMID- 30238552
TI  - Dopaminergic induction of human adipose-derived mesenchymal stem cells is
      accompanied by transcriptional activation of autophagy.
AB  - Neural differentiation involves drastic morphological alterations, essentially
      performed by a cell-homeostasis maintaining process known as autophagy. Here, we
      used the cocktail of choroid plexus epithelial cell-conditioned medium (CPEC-CM)
      and 15% knockout serum (KS) to induce human adipose-derived mesenchymal stem
      cells (hASCs) into tyrosine hydroxylase (TH)-positive neuron like cells. We
      showed that upon this induction, autophagy pathway was transcriptionally
      triggered. The expression levels of autophagy markers mTOR, BECN1, and MAP1LC3
      were evidently changed throughout the dopaminergic (DAergic) differentiation of
      hASCs, highlighting the critical role of autophagy in this process at the level
      of transcription.

PMID- 30238553
TI  - Microstructure characteristics and mechanical properties of Meretrix lusoria
      shell.
AB  - : The microstructure and mechanical properties of Meretrix lusoria shell were
      investigated. M. lusoria shell was comprised of three layers (outer layer, middle
      layer and inner layer). Outer layer with serried mastoid structure enhanced the
      connection strength with middle layer. The middle layer consisted of blocky
      pattern structure with porosity and crossed-lamellar structure. The inner layer
      exhibited the typical crossed-lamellar structure. Combined with structure
      characteristic, phase of aragonite confirmed the crossed-lamellar structure
      further, building material base for mechanical properties including flexure
      strength (296.26 MPa), compression strength (6.71 MPa) and crack arrest ability.
      Microstructure of the shell was the function base of crack deflection phenomenon,
      which dispersed and defused the applied load via the change of crack extension
      direction. The investigation of M. lusoria shell provided bionic models for the
      design and fabrication of bioinspired composites in engineering fields. RESEARCH
      HIGHLIGHTS: Microstructure and mechanical properties of Meretrix lusoria shell
      were investigated. Crossed-lamellar structure was the microstructure
      characterization. M. lusoria shell owned high flexure strength and crack arrest
      property.

PMID- 30238554
TI  - Ky-2, a hybrid compound histone deacetylase inhibitor, regulated inflammatory
      response in LPS-driven human macrophages.
AB  - Histone deacetylase has attracted much attention as an epigenetic factor, and the
      modulation of histone and transcription factor acetylation status is important
      for regulating gene expression. Moreover, histone deacetylase inhibitors are
      involved in cellular growth and differentiation. In the present study, we
      examined the effects of Ky-2, a hybrid-compound HDAC inhibitor, on inflammatory
      reactions and the polarization of macrophages in vitro. Human monocyte-like THP-1
      cells were polarized to macrophage-like cells using phorbol 12-myristate 13
      acetate, and then polarized to M1 macrophages with LPS. Ky-2 inhibited HDAC2
      expression and enhanced the acetylation of histone H3 in THP-1 cells. It also
      downregulated the expression of the IL-1beta-encoding gene and the LPS-induced
      phosphorylation of p38 mitogen-activated protein kinases in THP-1 cells.
      Moreover, the expression of nod-like receptor protein 3 and cleaved caspase-1 p20
      was downregulated in Ky-2-treated THP-1 cells. In contrast, this agent
      upregulated the expression of IL-1ra in LPS-treated THP-1 cells. These results
      indicate that Ky-2-treatment downregulates the expression of the inflammatory
      cytokine, IL-1beta, in LPS-treated THP-1 cells, suggesting that Ky-2 might
      regulate M1 macrophage polarization through the suppression of inflammatory
      responses such as NLRP3 inflammasome activation.

PMID- 30238555
TI  - Developmental anatomy of anomalous structure and classification of commercial
      specifications and grades of the Astragalus membranaceus var. mongholicus.
AB  - : The Daodi herb, Huangqi from Shanxi, is derived from the root of Astragalus
      membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. Huangqi was divided
      into different commercial specifications and grades in producing area according
      to macroscopic features. Developmental anatomy of anomalous structure of the
      perennial fresh main root of A. membranaceus var. mongholicus was investigated
      using conventional paraffin section to explore the relationship between anomalous
      structure and classification of commercial specifications and grades of Huangqi.
      The results of developmental anatomy showed that parenchyma cells in secondary
      phloem and secondary xylem of the perennial fresh main root regained meristematic
      ability, and resulted in anomalous structure. Several layers of additional
      periderm could sometimes be found in the secondary phloem near the initial
      periderm, which was called rhytidome. Additional periderm could sometimes be
      observed in the center of secondary xylem, which was described as "rotten heart."
      The area of rhytidome and "rotten heart" increased gradually with increasing age.
      The results of different commercial specifications and grades of Huangqi revealed
      rhytidome and "rotten heart" mainly existed in Ge-Da-Tou, Er-Dao-Tou, Hong-Lan
      Qi, Special Class, First Class, and Second Class. The additional periderm in
      secondary phloem of Ge-Da-Tou, Er-Dao-Tou, Hong-Lan-Qi, and Special Class could
      reach five layers; however, that of First Class and Second Class was three layers
      at most. In summary, this study demonstrated the rules of the development of
      rhytidome and "rotten heart" in A. membranaceus var. mongholicus. The
      relationship between anomalous structure and different commercial specifications
      and grades of Daodi herb Huangqi, was clarified. RESEARCH HIGHLIGHTS: The
      rhytidome and the development of "rotten heart" have not been reported in
      Astragalus membranaceus var. mongholicus. At present article, we demonstrated the
      developmental anatomy of the rhytidome and "rotten heart" existed in the
      secondary phloem and secondary xylem of the root of A. membranaceus var.
      mongholicus respectively. The rhytidome and "rotten heart" is different among six
      commercial specifications and grades of Huangqi.

PMID- 30238556
TI  - Light sheet microscopy with high spatial resolution based on polarized structured
      illumination beam modulated by the phase mask.
AB  - In this article, we present a method to improve axial resolution and expand the
      field of view of conventional light sheet fluorescence microscopy (LSFM) by phase
      modulation of the illumination beam. We added a bisected annular binary phase
      mask on the illumination path to modulate the radially polarized beam. The
      central spot of the modulated point spread function is narrower than that of
      Gaussian focus, although the sidelobe energy is increased. Then, a diffraction
      grating is used to produce multiple copies of this illumination pattern, and
      these pattern copies form the light sheet. By matching the numerical apertures of
      illumination lens and detection lens, the sidelobes on the detection axis can be
      suppressed in the captured data, although they do still contribute to
      photobleaching and phototoxicity in the sample. The simulation results show that
      the proposed method effectively reduces the thickness of the light sheet by 1.3
      times, and increase the length of the light sheet by two times compared with
      conventional LSFM.

PMID- 30238557
TI  - Oral vitamin D3 5000 IU/day as an adjuvant in the treatment of atopic dermatitis:
      a randomized control trial.
AB  - BACKGROUND: Vitamin D has immunomodulatory effects both in the innate and
      adaptive immune systems, and there is growing scientific evidence demonstrating
      its relevance in inflammatory processes such as AD. HYPOTHESIS: If vitamin D3
      promotes the skin immune system, then it should improve the response to treatment
      of patients with AD. METHODS: A randomized, double-blind placebo-controlled
      clinical trial was conducted, which included 65 patients with AD according to
      Hanifin-Rajka criteria and the severity scale (SCORAD). The patients were divided
      into two groups to receive either vitamin D3 5000 IU/day (n = 33) or placebo (n =
      32), plus baseline therapy (topical steroid, soap substitute, and emollient)
      during 3 months. RESULTS: Fifty-eight of the 65 enrolled subjects were included
      in the analysis. At the end of the intervention, the treated group achieved
      higher levels of 25(OH)D (P < 0.001). At week 12, those patients who registered
      serum levels of 25(OH)D >=20 ng/ml, regardless of whether or not they had
      received supplementation, showed a lower SCORAD compared to those with levels <20
      ng/ml (P < 0.001). Eighty percent of the patients with serum levels <20 ng/ml (n
      = 9) had moderate-severe AD despite standard treatment. Vitamin D levels >=20
      ng/ml associated with baseline therapy strongly favored remission of atopic
      dermatitis (P = 0.03). No significant differences were found between patients
      with serum levels of >=20 ng/ml vs. >=30 ng/ml. CONCLUSIONS: Reaching serum
      levels of 25(OH)D > 20 ng/ml in conjunction with standard therapy is sufficient
      to achieve a reduction in severity (SCORAD) in patients with AD.

PMID- 30238558
TI  - Initial modelling and updates on cost effectiveness from the first 10 years of a
      spleen registry.
AB  - OBJECTIVE: To validate our estimates from our original model and re-evaluate the
      cost-effectiveness of Spleen Australia, the Australian post-splenectomy registry,
      using our original model with updated model parameters based on advances in the
      literature and experience of the registry over the past decade. METHODS: We
      revisited a decision model from 2005, comparing 1,000 hypothetical registered
      patients with asplenia or hyposplenism against 1,000 who were not registered, and
      updated the model parameters. The cost-effectiveness of the registry was
      evaluated from a healthcare perspective in terms of additional cost per case of
      overwhelming post-splenectomy infection (OPSI) avoided and as additional cost per
      life year gained. RESULTS: Over a cohort lifetime the registry was associated
      with an additional cost of $125,724 per case of OPSI avoided or $19,286 per life
      year gained. CONCLUSIONS: Despite our initial over-estimation of immunisation and
      chemoprophylaxis uptake and increases in unit costs, our re-evaluation confirmed
      use of the registry to be cost-effective. Implications for public health:
      Improved outcomes for patients with asplenia or hyposplenism can be achieved by a
      cost-effective registry. Additional research into effectiveness of interventions,
      OPSI prevalence associated with varying intervention use, and compliance rates
      over time after registration would provide improved accuracy of cost
      effectiveness estimates.

PMID- 30238559
TI  - Surface morphological and physical characterizations of glass ionomer cements
      after sterilization processes.
AB  - : The aim of this study was to investigate if sterilization methods would promote
      changes in the selected adhesion-related surface properties of glass ionomer
      cements (GICs). Riva self-cure (RSC) and Riva light-cure (RLC) GICs were tested.
      Thirty samples were prepared according to the type of material (RSC and RLC) and
      sterilization method: hydrogen peroxide gas plasma (HPGP), steam sterilization
      (SS), and no sterilization (n = 5 per group). A Teflon matrix (5 * 2 mm) was
      filled with one of the GICs to produce the samples. For the groups with the RLC
      material, the samples were light cured using a light curing unit for 20 s. After
      24 hr, finishing and polishing were performed in all samples and then they were
      sterilized. Surface roughness, wettability, and micromorphology were accessed
      using a profilometer, a goniometer, and a scanning electron microscopy,
      respectively. Data were statistically analyzed through a two-way ANOVA and Tukey
      post-hoc test (p < .05). Both sterilization methods promoted similar roughness
      values to the nonsterilized samples (p > .05). HPGP decreased contact angle for
      RSC (p < .01), and SS increased contact angle for RLC (p < .01). Samples
      subjected to HPGP presented similar surface micromorphology to nonsterilized
      ones, regardless of the material. SS promoted exposition of smaller filler
      particles in both materials. Although sterilization methods did not alter surface
      roughness and wettability, the sterilization methods selectively altered the
      micromorphology of the materials tested. RESEARCH HIGHLIGHTS: This study's main
      finding suggests that each sterilization method altered the surface of glass
      ionomers in different ways. Thus, the choice of sterilization methods prior to
      bacterial adhesion can lead to a bias in antimicrobial studies.

PMID- 30238560
TI  - Assessing the generality and durability of interview-informed functional analyses
      and treatment.
AB  - Due to the limited research demonstrating socially valid outcomes of function
      based treatments in ecologically relevant environments (Santiago, Hanley, Moore,
      & Jin, 2016), we replicated and extended the effects of the interview-informed
      functional analysis and skill-based treatment procedure described by Hanley, Jin,
      Vanselow, and Hanratty (2014) with two children diagnosed with autism in a home
      setting. The assessment and treatment was implemented by a home-based service
      provider and treatment was extended to the participants' parents. Following the
      interview-informed functional analyses, we taught the participants functional
      communication responses and to engage in less-preferred activities when
      functional communication outcomes were delayed. We observed large reductions in
      problem behavior following the introduction of the function-based treatment. The
      effects extended to novel settings, stimuli, and caregivers and the results
      maintained at 6-week follow-ups.

PMID- 30238561
TI  - Structural organization of the olfactory organ in an amphihaline migratory fish
      Hilsa, Tenualosa ilisha.
AB  - : The histological as well as ultramicroscopic structures of olfactory system of
      an amphihaline migratory fish hilsa Tenualosa ilisha, were studied. The sexually
      matured riverine fish were collected from a common breeding habitat-the Hooghly,
      a tributary of river Ganga, West Bengal, India. This study revealed that the
      riverine hilsa has larger olfactory bulb compared to marine hilsa with the
      olfactory lobes well exposed through nostrils. The olfactory lamellae (OL) are 40
      45 in number and posses three distinct layers of sensory cells across each
      lamellae, namely, outer receptor cells (RC), middle sensory cells, and inner
      basal cells (BC). Besides the above arrangement, the sensory part of olfactory
      epithelium (OE) also bears rich microvillous cells exposed to the surface of the
      OE. The sensory and non-sensory surfaces on OL are distinguishable, with clear
      dendritic cells on sensory epithelium and solitary chemosensory cells on non
      sensory OE. Abundance of both types of cells in the OE is an indication of its
      chemoattraction ability towards molecules of amino acid origin. The feature of
      having abundant, dense, and large dendritic knobs on the surface of OE describes
      resemblance to the typical morphology of the chemosensory septal organs neuron.
      The expression of four G protein subunits, like Galphas/olf, Galphaq, Galphao,
      and Galphai-3 in OE indicate that its olfaction is a functional attributes of two
      olfactory systems, namely main olfactory system and Vomaronasal Olfactory System.
      Expression of ACIII and PLCbeta2 in OE further confirms two signaling pathways
      involved in odorant reception in hilsa. RESEARCH HIGHLIGHTS: The olfactory bulb
      in the amphihaline migratory fish hilsa is big in size, with 40-45 lamellae. Its
      sensory areas showed multilayered cellular features with prominent sensory as
      well as microvillous cells, whereas non-sensory area possesses solitary
      chemosensory cells. The expression of four G protein subunits, Galphas/olf,
      Galphaq, Galphao, and Galphai-3 in olfactory epithelium indicates that its
      olfaction is a functional attributes of two olfactory systems, namely main
      olfactory system and vomaronasal olfactory system.

PMID- 30238563
TI  - Quantitative characterization and diagnosis via hard X-ray phase-contrast
      microtomography.
AB  - Nondestructive three-dimensional (3D) micromorphological imaging technique is
      essential for hepatic alveolar echinococcosis (HAE) disease to determine its
      damage level and early diagnosis, assess relative drug therapy and optimize
      treatment strategies. However, the existing morphological researches of HAE
      mainly depend on the conventional CT, MRI, or ultrasound in hospitals,
      unfortunately confronting with the common limit of imaging resolution and
      sensitivity, especially for tiny or early HAE lesions. Now we presented a phase
      retrieval-based synchrotron X-ray phase computed tomography (PR-XPCT) with
      striking contrast-to-noise ratio and high-density resolution to visualize the HAE
      nondestructive 3D structures and quantitatively segment different pathological
      characteristics of HAE lesions without staining process at the micrometer scale.
      Our experimental results of the HAE rat models at early and developed
      pathological stages and albendazole liposome (L-ABZ) therapeutic feeding models
      successfully exhibited the different HAE pathological 3D morphological and
      microstructural characteristics with excellent contrast and high resolution,
      demonstrating its availability and superiority. Moreover, we achieved the
      quantitative statistics and analysis of the pathological changes of HAE lesions
      at different stages and L-ABZ therapeutic evaluation, helpful to understanding
      the development and drug treatment of HAE disease. The PR-XPCT-based quantitative
      segmentation and characterization has a great potential in detection and analysis
      of soft tissue pathological changes, such as different tumors.

PMID- 30238562
TI  - Long non-coding RNA MIF-AS1 promotes gastric cancer cell proliferation and
      reduces apoptosis to upregulate NDUFA4.
AB  - Long non-coding RNA MIF-AS1 (lncMIF-AS1) has been found to be upregulated in the
      tumor tissues of gastric cancer; however, its importance for the progression of
      gastric cancer remains unknown. Thus, the present study was designed to determine
      the role of the lncMIF-AS1-based signal transduction pathway in mediating the
      proliferation and apoptosis of gastric cancer cells. Differentially expressed
      lncRNAs and mRNAs were screened out using microarray analysis, based on the
      published data (GSE63288), and validated using quantitative RT-PCR. Target
      relationships between lncRNA-micro RNA (miRNA) and miRNA-mRNA were predicted by
      bioinformatics analysis and verified by dual-luciferase reporter assay. Protein
      expression of NDUFA4, COX6C and COX5B was detected by western blot. Cell
      proliferation, cell cycle and apoptosis were determined using colony formation
      assay and flow cytometry analysis. Oxidative phosphorylation in gastric cancer
      cells was assessed by levels of oxygen consumption and ATP synthase activity.
      Expression of lncMIF-AS1 and NDUFA4 were upregulated in gastric cancer tissues
      and cells as compared with non-cancerous gastric tissues and cells (P < .05). MiR
      212-5p was identified as the most important miRNA linker between lncMIF-AS1 and
      NDUFA4, which was negatively regulated by lncMIF-AS1 and its depletion is the
      main cause of NDUFA4 overexpression (P < .01). The upregulated expression of
      NDUFA4 then greatly promoted the proliferation and decreased the apoptosis of
      gastric cancer cells through activation of the oxidative phosphorylation pathway.
      Taken together, the present study implies that inhibition of lncMIF-AS1/miR-212
      5p/NDUFA4 signal transduction may provide a promising therapeutic target for the
      treatment of gastric cancer.

PMID- 30238565
TI  - Loss of only the smallest patches will reduce species diversity in most discrete
      habitat networks.
AB  - Under many global-change scenarios, small habitat patches are the most vulnerable
      to destruction. For example, smaller ponds are at greater risk in a drying
      climate and their loss would remove any obligate aquatic individuals present. We
      asked what proportional loss of species diversity from metacommunities comprised
      of discrete habitat patches should be expected from attrition (complete loss) of
      only the smallest patches under such a premise. We analyzed 175 published
      datasets for different taxonomic groups (vertebrates, invertebrates, and plants)
      and habitat types (islands, habitat islands, and fragments). We simulated the
      destruction of only the smallest patches to an approximate 20% of total area
      (range: 15.2%-24.2%) and analyzed species loss. Mean [+/- 95% CI] species loss
      was 12.7% [10.8, 14.6], although 18.3% of datasets lost no species. Four broad
      patterns of species loss were evident, reflecting underlying differences in
      minimum area requirements and the degree of species turnover among patches.
      Regression modeling showed species loss increased with greater species turnover
      among patches (betaSIM ) and decreased with greater area scaling of diversity
      (i.e., larger power-law island species-area relationship exponents). Losses also
      increased with greater numbers of single-patch endemics and with increasing
      proportions of patches destroyed. After accounting for these predictors, neither
      taxonomic group nor habitat type increased explained variation in species loss.
      Attrition of the smallest patches removed species in >80% of metacommunities,
      despite all larger patches and >75% of total area remaining intact. At both 10%
      and 20% area reduction, median species loss across all datasets was around 50%
      higher than predicted from methods based on the species-area relationship. We
      conclude that any mechanism of global change that selectively destroys small
      habitat patches will lead to imminent extinctions in most discrete
      metacommunities.

PMID- 30238564
TI  - RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer
      cell growth in a preclinical model.
AB  - Aberrant activation of Wnt/beta-catenin signaling causes tumorigenesis and
      promotes the proliferation of colorectal cancer cells. Porcupine inhibitors,
      which block secretion of Wnt ligands, may have only limited clinical impact for
      the treatment of colorectal cancer, because most colorectal cancer is caused by
      loss-of-function mutations of the tumor suppressor adenomatous polyposis coli
      (APC) downstream of Wnt ligands. Tankyrase poly(ADP-ribosyl)ates (PARylates)
      Axin, a negative regulator of beta-catenin. This post-translational modification
      causes ubiquitin-dependent degradation of Axin, resulting in beta-catenin
      accumulation. Tankyrase inhibitors downregulate beta-catenin and suppress the
      growth of APC-mutated colorectal cancer cells. Herein, we report a novel
      tankyrase-specific inhibitor RK-287107, which inhibits tankyrase-1 and -2 four-
      and eight-fold more potently, respectively, than G007-LK, a tankyrase inhibitor
      that has been previously reported as effective in mouse xenograft models. RK
      287107 causes Axin2 accumulation and downregulates beta-catenin, T-cell
      factor/lymphoid enhancer factor reporter activity and the target gene expression
      in colorectal cancer cells harboring the shortly truncated APC mutations.
      Consistently, RK-287107 inhibits the growth of APC-mutated (beta-catenin
      dependent) colorectal cancer COLO-320DM and SW403 cells but not the APC-wild
      (beta-catenin-independent) colorectal cancer RKO cells. Intraperitoneal or oral
      administration of RK-287107 suppresses COLO-320DM tumor growth in NOD-SCID mice.
      Rates of tumor growth inhibition showed good correlation with the behavior of
      pharmacodynamic biomarkers, such as Axin2 accumulation and MYC downregulation.
      These observations indicate that RK-287107 exerts a proof-of-concept antitumor
      effect, and thus may have potential for tankyrase-directed molecular cancer
      therapy.

PMID- 30238566
TI  - Land surface greening suggests vigorous woody regrowth throughout European semi
      natural vegetation.
AB  - The satellite record has revealed substantial land surface "greening" in the
      northern hemisphere over recent decades. Process-based Earth system models (ESMs)
      attribute enhanced vegetation productivity (greening) to CO2 fertilisation.
      However, the models poorly reproduce observed spatial patterns of greening,
      suggesting that they ignore crucial processes. Here, we explore whether fine
      scale land cover dynamics, as modified by ecological and land-use processes, can
      explain the discrepancy between models and satellite-based estimates of greening.
      We used 500 m satellite-derived Leaf Area Index (LAI) to quantify greening. We
      focus on semi-natural vegetation in Europe, and distinguish between conservation
      areas and unprotected land. Within these ecological and land-use categories, we
      then explored the relationships between vegetation change and major climatic
      gradients. Despite the relatively short time-series (15 years), we found a strong
      overall increase in LAI (i.e., greening) across all European semi-natural
      vegetation types. The spatial pattern of vegetation change identifies land-use
      change, particularly land abandonment, as a major initiator of vegetation change
      both in- and outside of protected areas. The strongest LAI increases were
      observed in mild climates, consistent with more vigorous woody regrowth after
      cessation of intensive management in these environments. Surprisingly, rates of
      vegetation change within protected areas did not differ significantly from
      unprotected semi-natural vegetation. Overall, the detected LAI increases are
      consistent with previous, coarser-scale, studies. The evidence indicates that
      woody regrowth following land abandonment is an important driver of land surface
      greening throughout Europe. The results offer an explanation for the large
      discrepancies between ESM-derived and satellite-derived greening estimates and
      thus generate new avenues for improving the ESMs on which we rely for crucial
      climate forecasts.

PMID- 30238567
TI  - New therapeutic vision of nutrition in dermatology: Integrative nutrition.
AB  - Many skin disorders have been associated with nutritional deficiencies, as well
      as many skin disorders, have been associated to diet-related immune mechanisms.
      The food can be a source of beneficial substances for health that act in very
      precise ways on the body and the functioning of each individual cells, tissues,
      and organs.

PMID- 30238569
TI  - Tomato floral induction and flower development are orchestrated by the interplay
      between gibberellin and two unrelated microRNA-controlled modules.
AB  - Age-regulated microRNA156 (miR156) and targets similarly control the competence
      to flower in diverse species. By contrast, the diterpene hormone gibberellin (GA)
      and the microRNA319-regulated TEOSINTE BRANCHED/CYCLOIDEA/PCF (TCP) transcription
      factors promote flowering in the facultative long-day Arabidopsis thaliana, but
      suppress it in the day-neutral tomato (Solanum lycopersicum). We combined genetic
      and molecular studies and described a new interplay between GA and two unrelated
      miRNA-associated pathways that modulates tomato transition to flowering. Tomato
      PROCERA/DELLA activity is required to promote flowering along with the miR156
      targeted SQUAMOSA PROMOTER BINDING-LIKE (SPL/SBP) transcription factors by
      activating SINGLE FLOWER TRUSS (SFT) in the leaves and the MADS-Box gene
      APETALA1(AP1)/MC at the shoot apex. Conversely, miR319-targeted LANCEOLATE
      represses floral transition by increasing GA concentrations and inactivating SFT
      in the leaves and AP1/MC at the shoot apex. Importantly, the combination of high
      GA concentrations/responses with the loss of SPL/SPB function impaired canonical
      meristem maturation and flower initiation in tomato. Our results reveal a
      cooperative regulation of tomato floral induction and flower development,
      integrating age cues (miR156 module) with GA responses and miR319-controlled
      pathways. Importantly, this study contributes to elucidate the mechanisms
      underlying the effects of GA in controlling flowering time in a day-neutral
      species.

PMID- 30238570
TI  - Epigenetic dysregulation in hepatocellular carcinoma: an up-to-date review.
AB  - Due to the advances made in research based on next generation sequencers, it is
      now possible to detect and analyze epigenetic abnormalities associated with
      cancer. DNA methylation, various histone modifications, chromatin remodeling, and
      non-coding RNA-associated gene silencing are considered to be transcriptional
      regulatory mechanisms associated with gene expression changes. The breakdown of
      this precise regulatory system is involved in the transition to cancer. The
      important role of epigenetic regulation can be observed from the high rate of
      genetic mutations and abnormal gene expression leading to a breakdown in
      epigenetic gene expression regulation seen in hepatocellular carcinoma (HCC).
      Based on an understanding of epigenomic abnormalities associated with
      pathological conditions, these findings will lead the way to diagnosis and
      treatment. In particular, in addition to the fact that there are few choices in
      terms of extant drug therapies aimed at HCC, there are limits to their antitumor
      effects. The clinical application of epigenetic therapeutic agents for HCC has
      only just begun, and future developments are expected.

PMID- 30238568
TI  - High-intensity cannabis use is associated with retention in opioid agonist
      treatment: a longitudinal analysis.
AB  - BACKGROUND AND AIMS: Cannabis use is common among people on opioid agonist
      treatment (OAT), causing concern for some care providers. However, there is
      limited and conflicting evidence on the impact of cannabis use on OAT outcomes.
      Given the critical role of retention in OAT in reducing opioid-related morbidity
      and mortality, we aimed to estimate the association of at least daily cannabis
      use on the likelihood of retention in treatment among people initiating OAT. As a
      secondary aim we tested the impacts of less frequent cannabis use. DESIGN: Data
      were drawn from two community-recruited prospective cohorts of people who use
      illicit drugs (PWUD). Participants were followed for a median of 81 months
      (interquartile range = 37-130). SETTING: Vancouver, Canada. PARTICIPANTS: This
      study comprised a total of 820 PWUD (57.8% men, 59.4% of Caucasian ethnicity,
      32.2% HIV-positive) initiating OAT between December 1996 and May 2016. The
      proportion of women was higher among HIV-negative participants, with no other
      significant differences. MEASUREMENTS: The primary outcome was retention in OAT,
      defined as remaining in OAT (methadone or buprenorphine/naloxone-based) for two
      consecutive 6-month follow-up periods. The primary explanatory variable was
      cannabis use (at least daily versus less than daily) during the same 6-month
      period. Confounders assessed included: socio-demographic characteristics,
      substance use patterns and social-structural exposures. FINDINGS: In adjusted
      analysis, at least daily cannabis use was positively associated with retention in
      OAT [adjusted odds ratio (aOR) = 1.21, 95% confidence interval (CI) = 1.04-1.41].
      Our secondary analysis showed that compared with non-cannabis users, at least
      daily users had increased odds of retention in OAT (aOR = 1.20, 95% CI = 1.02
      1.43), but not less than daily users (aOR = 1.00, 95% CI = 0.87-1.14).
      CONCLUSIONS: Among people who use illicit drugs initiating opioid agonist
      treatment in Vancouver, at least daily cannabis use was associated with
      approximately 21% greater odds of retention in treatment compared with less than
      daily consumption.

PMID- 30238572
TI  - Conceptualizing skill mix in nursing and health care: An analysis.
AB  - AIM: This paper aims to unpack the concept of "skill mix" into its constituent
      parts to achieve a better understanding and reduce confusion associated with the
      term. BACKGROUND: Skill mix is a topic that is widely debated and is foremost on
      the health policy agenda due to specific local pressures within international
      health services. At present, however, there is large variation in terms of what
      is understood by the concept of "skill mix" and there is a paucity of research
      that attempts to analyse this concept. EVALUATION: Using Rodgers' evolutionary
      method of concept analysis, this paper provides an analysis of definitions of
      skill mix, its attributes and associated terms in the literature. KEY ISSUE:
      Definitions of skill mix are often vague and ambiguous and may refer to one or
      more attributes of skill mix. CONCLUSION: A lack of understanding of the concept
      can lead to an ad hoc interpretation of policy recommendations related to skill
      mix at local level. IMPLICATIONS FOR NURSING MANAGEMENT: A better understanding
      of the concept of "skill mix" and its attributes can assist both policy makers
      and stakeholders, including nurse management, to ensure that the potential of
      skill mix is maximized.

PMID- 30238573
TI  - The Effect of Peripheral Neuromodulation on Pain From the Sacroiliac Joint: A
      Retrospective Cohort Study.
AB  - OBJECTIVE: To report a retrospective review of the longer-term results of
      peripheral neuromodulation in 12 patients with significant chronic sacroiliac
      joint pain who had previously failed multiple conservative and interventional
      pain therapies. METHODS: To allow for the assessment of meaningful longer-term
      outcome, implants for all 12 patients had been in place for a minimum of 18
      months to a maximum of 36 months prior to the formal review. RESULTS: Compared to
      the preimplantation baseline, the longer-term follow-up revealed a significant
      and sustained reduction in visual analog scale pain scores from 8.7T 1.1 to 1.1T
      1.0 (p < 0.001), with a 75% reduction in analgesia requirement, and improvement
      in pain impact on daily function from 94.1% T 5.9% to 5.8% T 6.0% (p < 0.001).
      CONCLUSION: This initial case series has highlighted that SIJ neuromodulation
      results in the reduction in pain intensity and improved functionality in patients
      who have already failed conventional medical management and interventional
      techniques, including RF denervation. These preliminary results merit a
      prospective randomized trial of peripheral neuromodulation.

PMID- 30238574
TI  - Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure
      with Volume Overload) trial.
AB  - AIMS: Decisive evidence on the optimal diuretic agent, dosing schedule, and
      administration route is lacking in acute heart failure (AHF) with congestion. The
      Acetazolamide in Decompensated heart failure with Volume OveRload (ADVOR) trial
      is designed to test the hypothesis that the carbonic anhydrase inhibitor
      acetazolamide, a potent inhibitor of proximal tubular sodium reabsorption,
      improves decongestion when combined with loop diuretic therapy in AHF,
      potentially leading to better clinical outcomes. METHODS: The ADVOR trial is set
      up as a multicentre, randomized, double-blind, placebo-controlled study, aiming
      to recruit 519 patients with AHF and clinically evident volume overload. All
      study participants receive high-dose intravenous loop diuretics as background
      therapy and are randomized towards intravenous acetazolamide at a dose of 500 mg
      once daily vs. placebo, stratified according to including study centre and
      ejection fraction (< 40% vs. >= 40%). The primary endpoint is successful
      decongestion with no more than trace oedema assessed on the third morning after
      hospital admission, with good diuretic efficacy defined as a urine output > 3.5 L
      during the first 30-48 h of decongestive treatment. Secondary endpoints include
      all-cause mortality or heart failure readmission after 3 months, length of
      hospital stay for the index admission, and longitudinal changes in the EuroQol-5
      dimensions questionnaire. CONCLUSION: ADVOR will investigate if acetazolamide
      combined with loop diuretic therapy improves decongestion in AHF with volume
      overload.

PMID- 30238571
TI  - Shortening self-report mental health symptom measures through optimal test
      assembly methods: Development and validation of the Patient Health Questionnaire
      Depression-4.
AB  - BACKGROUND: The objective of this study was to develop and validate a short form
      of the Patient Health Questionnaire-9 (PHQ-9), a self-report questionnaire for
      assessing depressive symptomatology, using objective criteria. METHODS: Responses
      on the PHQ-9 were obtained from 7,850 English-speaking participants enrolled in
      20 primary diagnostic test accuracy studies. PHQ unidimensionality was verified
      using confirmatory factor analysis, and an item response theory model was fit.
      Optimal test assembly (OTA) methods identified a maximally precise short form for
      each possible length between one and eight items, including and excluding the
      ninth item. The final short form was selected based on prespecified validity,
      reliability, and diagnostic accuracy criteria. RESULTS: A four-item short form of
      the PHQ (PHQ-Dep-4) was selected. The PHQ-Dep-4 had a Cronbach's alpha of 0.805.
      Sensitivity and specificity of the PHQ-Dep-4 were 0.788 and 0.837, respectively,
      and were statistically equivalent to the PHQ-9 (sensitivity = 0.761, specificity
      = 0.866). The correlation of total scores with the full PHQ-9 was high (r =
      0.919). CONCLUSION: The PHQ-Dep-4 is a valid short form with minimal loss of
      information of scores when compared to the full-length PHQ-9. Although OTA
      methods have been used to shorten patient-reported outcome measures based on
      objective, prespecified criteria, further studies are required to validate this
      general procedure for broader use in health research. Furthermore, due to
      unexamined heterogeneity, there is a need to replicate the results of this study
      in different patient populations.

PMID- 30238575
TI  - Facile Synthesis of a Stable Dihydroboryl {BH2 }- Anion.
AB  - While the one-electron reduction of (CAACMe )BH2 Br (CAACMe =1-(2,6
      diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene) yields a hydride
      shift isomer of the corresponding tetrahydrodiborane, a further reversible
      reduction leads to the first stable parent boryl anion, [(CAACMe )BH2 ]- , which
      acts as a powerful boron nucleophile.

PMID- 30238576
TI  - Sweet syndrome following a positive Mantoux test due to pulmonary tuberculosis.

PMID- 30238577
TI  - Early worsening of diabetic retinopathy due to intensive glycaemic control.
AB  - The prevalence of diabetes and diabetic retinopathy is increasing around the
      world. Glycaemic control is important in reducing the long-term risk of
      complications of diabetes, however intensive glycaemic control, particularly in
      patients with longstanding and poorly controlled diabetes, is associated with the
      risk of early worsening of diabetic retinopathy and vision loss. We present two
      clinical cases to illustrate the presentation of early worsening and to highlight
      a role for intravitreal anti-vascular endothelial growth factor therapies in
      ameliorating this phenomenon, as well as a review of the current understanding of
      this phenomenon. We emphasise the importance of identifying individuals at risk
      of early worsening of diabetic retinopathy and recommend regular ophthalmological
      review during the period of intensive glycaemic control to ensure optimal visual
      outcomes.

PMID- 30238578
TI  - Recurrent Merkel cell carcinoma of the gluteal region: A case report.
AB  - Merkel cell carcinoma (MCC) is a rare malignant tumor of the skin. The
      development of MCC on non-sun-exposed skin is extremely rare, with few cases
      reported in the literature. The present authors aimed to highlight the
      characteristic features and treatment options of this tumor. The present authors
      present a 50-year-old man who developed MCC on the left gluteal region (non-sun
      exposed skin). After surgery with clear margins, adjuvant radiotherapy was given.
      Three months after radiotherapy, lymphatic recurrence was observed and he was
      treated with chemotherapy. On follow-up, systemic metastases were found and
      palliative treatment was planned.

PMID- 30238579
TI  - "Chemical" surgery in treating basal cell carcinoma in elderly.
AB  - The incidence of basal cell carcinoma (BCC) has been increasing in the last
      decades due to population aging and precise diagnosis. The difficulty that
      physicians face frequently is related to the treatment decision for BCC; when
      treating BCC, correct and personalized choices must be taken into consideration
      by selecting from a large variety of therapeutic options such as: surgical
      excision ("the golden standard therapy"), electrodessication, cryosurgery,
      radiation therapy, laser, photodynamic therapy, curettage, topical treatment
      (imiquimod, 5-fluorouracil, vismodegib), or combining different treatments. The
      present authors present series of cases of patients diagnosed with BCC,
      highlighting that "chemical surgery" using 70% trichloroacetic acid could be a
      valuable option in the treatment of nonaggressive BCC of the face.

PMID- 30238580
TI  - Angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers
      induced pemphigus: A case series and literature review.
AB  - Pemphigus is a group of autoimmune diseases characterized by the formation of
      erosions and/or flaccid bullae of the skin and/or mucosae. The definition "drug
      induced pemphigus" has been coined to indicate cases of pemphigus with clinical,
      histological and immunopathologic features similar to those of the idiopathic
      disease but induced by systemic ingestion or local use of some drugs. The present
      authors analyzed a case series of three case reports with clinical and
      pharmacological features compatible with the diagnosis of angiotensin converting
      enzyme inhibitors or angiotensin II receptor blocker drug-induced pemphigus. The
      patients were visited by the dermatological Unit of Magna Graecia University in
      Catanzaro. All suspected drug induced pemphigus were treated by suspending the
      suspected drug and by starting a treatment with systemic corticosteroid drugs,
      leading to a remission of the clinical manifestations in some months. When a drug
      induced bullous disease is probable, it is necessary to interrupt the suspected
      substance and to start a high dose treatment with corticosteroid drugs to resolve
      the clinical case in a short period of time.

PMID- 30238581
TI  - Effect of pH and heating conditions on the properties of Alaska pollock (Theragra
      chalcogramma) surimi gel fortified with fish oil.
AB  - To improve the quality and functionality of emulsified surimi gels, the effect of
      pH and heating conditions on the properties of surimi gel fortified with fish oil
      was investigated. Results showed that pH conditions influenced the solubility and
      emulsifying properties of surimi proteins and that the gel properties were
      associated with the protein properties. Under direct heating, the highest gel
      strength was achieved at pH 8.0, in which condition the solubility was
      significantly higher than others. Higher emulsifying stability resulted in
      enhanced gel strength relative to that of the control group. However, the changes
      in the gel strength were not consistent under two-step heating. In addition, the
      expressible moisture and oil content were found to vary depending on the pH
      values under both heating conditions. The corresponding changes in expressible
      moisture and oil content could be attributed to the high protein solubility and
      emulsifying properties of surimi proteins. Analysis of the dynamic rheological
      properties of the resulting surimi paste revealed that the gelation properties
      varied depending on the pH conditions during the heating process. In addition,
      the temperatures of myosin cross-linking changed according to the structure of
      surimi proteins, which in turn varied depending on the pH conditions. PRACTICAL
      APPLICATIONS: To improve the functionality of surimi-based product, the fish oil
      was added to prepare surimi gel. pH and heating conditions play important roles
      in the gelation of fish proteins. Therefore, this study investigated the effect
      of combined pH and heating condition on the property of surimi gel fortified with
      fish oil. The emulsified surimi gel with fine texture was obtained at pH of 8
      8.5; moreover, heating conditions (direct heating and two-step heating) also
      influenced texture of emulsified surimi gel. These results provide the evidence
      to produce the emulsified surimi-based product with the high gel strength, water-
      and oil-holding capacity.

PMID- 30238583
TI  - Atopic-like dermatitis after secukinumab injection: A case report.

PMID- 30238582
TI  - Angioedema is an unfavorable factor for the response to omalizumab in chronic
      spontaneous urticaria: A retrospective study.
AB  - Antihistamines are the first-line treatment option for chronic urticaria. In
      recent years, omalizumab, an anti-immunoglobulin-E humanized monoclonal antibody,
      has been used in patients with recalcitrant disease. The present study aimed to
      retrospectively evaluate the efficacy and safety of omalizumab and determine
      whether there was a difference between complete and partial responses to
      omalizumab with respect to age, gender, disease duration and coexistence of
      angioedema. From May 2014 to December 2016, a total of 40 refractory chronic
      urticaria patients were treated with omalizumab. Complete response was observed
      in 19 (47.5%) patients, and partial response was observed in 18 (45%) patients.
      There were no statistically significant differences between the rates of complete
      and partial responses in patients with respect to gender, age, and disease
      duration. However, complete response was more frequent (60%) in patients without
      angioedema. Remission was observed in 40.5% (n = 15) of patients, and the follow
      up time was 5.5 +/- 2.4 months. There was a statistically significant association
      between remission and coexistence of angioedema (p < .05). Eighty-seven percent
      (13/15) of the remission patients did not have angioedema. Thus, omalizumab can
      be used effectively and safely in refractory chronic urticaria patients. However,
      the coexistence of angioedema may be an unfavorable factor for complete response
      and remission.

PMID- 30238584
TI  - A preliminary study of fractional CO2 laser added to topical tacrolimus combined
      with 308 nm excimer lamp for refractory vitiligo.
AB  - Fractional CO2 laser has been proposed recently to be effective and well
      tolerated in patients with refractory vitiligo. In this preliminary, prospective
      study, 21 patients with multiple, localized, refractory, non-segmental vitiligo
      lesions were randomized to receive either tacrolimus ointment plus 308 nm excimer
      lamp (control), with or without the addition of fractional CO2 laser. There was
      no statistically significant improvement in the repigmentation on the laser side
      compared to the control side. Treatment was generally well-tolerated; only
      localized adverse effects were noted. Overall the triple combination therapy was
      not superior to tacrolimus ointment plus 308 nm excimer lamp. Treatment failure
      may reflect insufficient penetration of tacrolimus ointment through the holes
      created by fractional CO2 laser on the skin.

PMID- 30238585
TI  - Direct Evidence of the Benzylium and Tropylium Cations as the Two Long-Lived
      Isomers of C7 H7.
AB  - Disentangling the isomeric structure of C7 H7 + is a longstanding experimental
      issue. We report here the full mid-infrared vibrational spectrum of C7 H7 +
      tagged with Ne obtained with infrared-predissociation spectroscopy at 10 K.
      Saturation depletion measurements were used to assign the contribution of
      benzylium and tropylium isomers and demonstrate that no other isomer is involved.
      Recorded spectral features compare well with density functional theory
      calculations. This opens perspectives for a better understanding and control of
      the formation paths leading to either tropylium or benzylium ions.

PMID- 30238586
TI  - CT sinogram-consistency learning for metal-induced beam hardening correction.
AB  - PURPOSE: This paper proposes a sinogram-consistency learning method to deal with
      beam hardening-related artifacts in polychromatic computerized tomography (CT).
      The presence of highly attenuating materials in the scan field causes an
      inconsistent sinogram that does not match the range space of the Radon transform.
      When the mismatched data are entered into the range space during CT
      reconstruction, streaking and shading artifacts are generated owing to the
      inherent nature of the inverse Radon transform METHODS: The proposed learning
      method aims to repair inconsistent sinogram by removing the primary metal-induced
      beam hardening factors along the metal trace in the sinogram. Taking account of
      the fundamental difficulty in obtaining sufficient training data in a medical
      environment, the learning method is designed to use simulated training data and a
      patient's implant type-specific learning model is used to simplify the learning
      process. RESULTS: The feasibility of the proposed method is investigated using a
      dataset, consisting of real CT scans of pelvises containing simulated hip
      prostheses. The anatomical areas in training and test data are different, in
      order to demonstrate that the proposed method extracts the beam hardening
      features, selectively. The results show that our method successfully corrects
      sinogram inconsistency by extracting beam hardening sources by means of deep
      learning. CONCLUSION: This paper proposed a deep learning method of sinogram
      correction for beam hardening reduction in CT for the first time. Conventional
      methods for beam hardening reduction are based on regularizations, and have the
      fundamental drawback of being not easily able to use manifold CT images, while a
      deep learning approach has the potential to do so.

PMID- 30238587
TI  - Topical diltiazem for ulceration of striae distensae associated with bevacizumab
      therapy.

PMID- 30238588
TI  - Prevalence of depressed mood and loss of interest among community-dwelling older
      people: Large-scale questionnaire survey and visiting intervention.
AB  - AIM: Late-life depression is identified less often by general practitioners than
      depression in younger adults, but failure to have late-life depression recognized
      in a primary care setting can have fatal consequences. The aim of the present
      study was to examine the prevalence of depressed mood and loss of interest, and
      identify associated factors among community-dwelling older adults in a large
      scale study. METHODS: A questionnaire was mailed to all residents (n = 132 005)
      aged >=65 years in one Tokyo district. The questionnaire asked about depressed
      mood and loss of interest. It also included items measuring sociodemographic
      variables, physical health-related variables, psychological variables,
      socioeconomic variables, attitude to the community and the Dementia Assessment
      Sheet for Community-based Integrated Care System - 21 items. RESULT: In total,
      19.5% of community-dwelling older people had experienced a depressed mood or loss
      of interest during the past month. This group also showed increased frailty and a
      negative attitude towards the community, and were less likely to be economically
      disadvantaged (although more likely to have had a childhood economic
      disadvantage). The multivariate analysis showed that increased frailty had the
      strongest relationship with depressed mood. Survey respondents who had either of
      these conditions were more likely to receive support from the community-based
      integrated support center. CONCLUSIONS: The present study showed a high
      prevalence of depressed mood and loss of interest among older people. Frailty was
      a significant factor, suggesting that collaboration is essential between primary
      care geriatrics and geriatric psychiatry. Geriatr Gerontol Int 2018; 18: 1567
      1572.

PMID- 30238589
TI  - Limbal squamous cell carcinoma in a Rocky Mountain Horse: Case report and
      investigation of genetic contribution.
AB  - OBJECTIVE: To document a case of limbal squamous cell carcinoma (SCC) in a Rocky
      Mountain Horse stallion determined to be homozygous for the genetic risk factor
      (DDB2 c.1013C>T) strongly associated with the disease in Haflinger and Belgian
      horses, and to determine the frequency of this allele in a larger population of
      Rocky Mountain Horses. ANIMALS STUDIED: One privately owned Rocky Mountain Horse
      and 84 Rocky Mountain Horses screened for allelic frequency. PROCEDURES: A
      complete ophthalmic examination was performed on a Rocky Mountain Horse stallion
      for assessment of a mass affecting the right eye. A clinical diagnosis of
      suspected limbal SCC was made, and routine keratoconjunctivectomy and adjunctive
      strontium irradiation were performed. Genotyping for the DDB2 c.1013C > T
      (rs1139682898) risk variant was performed utilizing an allele-specific PCR assay
      on DNA isolated from whole blood and hair follicles. RESULTS: Histopathology
      confirmed the limbal mass to be consistent with SCC. The horse was genotyped as
      homozygous for the DDB2 c.1013C >T risk variant. The frequency of the variant
      allele among a population of 84 Rocky Mountain Horses was found to be 0.20.
      CONCLUSION: The Rocky Mountain Horse breed possesses the DDB2 variant allele
      determined to be a significant risk factor for ocular SCC in the Haflinger and
      Belgian breeds. Genotyping additional Rocky Mountain Horses diagnosed with ocular
      SCC as well as confirmed healthy controls for this variant should be undertaken
      to determine whether a significant association exists between ocular SCC and the
      variant in the Rocky Mountain Horse breed.

PMID- 30238590
TI  - Investigation of small intestinal lesions in dialysis patients using capsule
      endoscopy.
AB  - INTRODUCTION: Although gastrointestinal hemorrhage is an important complication
      for dialysis patients, the details of many points remain unclear with regard to
      small intestinal lesions. METHODS: Capsule endoscopy was performed in fecal
      occult blood-positive dialysis (n =16) and non-dialysis (n = 20) patients after
      upper and lower gastrointestinal endoscopies failed to reveal hemorrhagic
      lesions. FINDINGS: Erosive lesions were observed in 50.0% (8/16) and 25.0% (5/20)
      of the dialysis and non-dialysis groups, respectively. Vascular lesions were
      observed in 62.5% (10/16) and 25.0% (5/20), respectively. Vascular lesions were
      observed at a significantly higher rate in the dialysis patients (P = 0.041), but
      no significant difference was noted in erosive lesions (P = 0.188). Of patients
      taking proton pump inhibitor (PPI), Non-Steroidal Anti-Inflammatory Drugs, and
      antiplatelet drugs, only oral PPI administration was associated with vascular
      lesions (P = 0.02). DISCUSSION: In dialysis patients, vascular lesions are the
      most common among small intestinal lesions, suggesting that they may have caused
      previously unexplained gastrointestinal hemorrhage in dialysis patients. It was
      also suggested that the frequent use of PPI may be a cause of small intestinal
      lesions.

PMID- 30238591
TI  - Beyond Hypnograms: Assessing Sleep Stability Using Acoustic and Electrical
      Stimulation.
AB  - OBJECTIVE: Conventional polysomnographic recordings reflect brain dynamics
      associated with sleep architecture. We hypothesized that noninvasive tools like
      transcranial alternating current stimulation (tACS) and acoustic stimulation (for
      generating event related potentials [ERPs]) would help to predict sleep stability
      and provide a window to actively assess brain activity during sleep. MATERIALS
      AND METHODS: Twelve healthy male volunteers participated in the multiple whole
      night polysomnography (PSG) recording protocol. Acoustic tones (100 msec
      duration) were presented throughout night to evaluate ERP during sleep.
      Furthermore, 30 sec tACS were presented during nonrapid eye movement (NREM) and
      rapid eye movement (REM) sleep on subsequent two nights without disturbing the
      subject's sleep. For ERP analysis, event-locked artifact-free epochs from each
      sleep stage were averaged separately. For tACS analysis, 30 sec prestimulus and
      poststimulus artifact-free EEG epochs were subjected to bootstrapping-based
      comparison of power spectral values. RESULTS: Acoustic stimulation generated
      sleep stage-dependent ERP components (N350, N550, and P900) in all participants.
      The tACS stimulation during NREM sleep (0.75 Hz) increased parietal delta power
      but decreased frontocentral theta and increased frontal gamma power when
      delivered during REM sleep (40Hz). These interventions provide details on sleep
      stability as larger N550-P900 ERP-complex correlated with lower NREM disruptions
      (Spearman's rho = -0.553; p = 0.049; n = 10) and tACS-related theta power
      perturbation with higher REM disruptions (Spearman's rho = 0.734; p = 0.030; n =
      7). CONCLUSIONS: Noninvasive brain stimulation approaches such as sleep ERP and
      sleep tACS are reliable tools to evaluate sleep stability during NREM and REM
      sleep, respectively, but more large-sample studies are warranted.

PMID- 30238592
TI  - Promoting an "Auteur Theory" for Young Scientists: Preserving Excitement and
      Creativity ....

PMID- 30238594
TI  - Interactions between low-socioeconomic status, adult influences on macronutrient
      intakes and childhood obesity.

PMID- 30238593
TI  - Redox-Active Reagents for Photocatalytic Generation of the OCF3 Radical and
      (Hetero)Aryl C-H Trifluoromethoxylation.
AB  - The trifluoromethoxy (OCF3 ) radical is of great importance in organic chemistry.
      Yet, the catalytic and selective generation of this radical at room temperature
      and pressure remains a longstanding challenge. Herein, the design and development
      of a redox-active cationic reagent (1) that enables the formation of the OCF3
      radical in a controllable, selective, and catalytic fashion under visible-light
      photocatalytic conditions is reported. More importantly, the reagent allows
      catalytic, intermolecular C-H trifluoromethoxylation of a broad array of
      (hetero)arenes and biorelevant compounds. Experimental and computational studies
      suggest single electron transfer (SET) from excited photoredox catalysts to 1
      resulting in exclusive liberation of the OCF3 radical. Addition of this radical
      to (hetero)arenes gives trifluoromethoxylated cyclohexadienyl radicals that are
      oxidized and deprotonated to afford the products of trifluoromethoxylation.

PMID- 30238595
TI  - Robotic-assisted subtotal colectomy for synchronous colon cancers in a patient
      with indeterminate colitis - a video vignette.

PMID- 30238596
TI  - Avenues to Characterize the Interactions of Extended N-Glycans with Proteins by
      NMR Spectroscopy: The Influenza Hemagglutinin Case.
AB  - Long-chain multiantenna N-glycans are extremely complex molecules. Their inherent
      flexibility and the presence of repetitions of monosaccharide units in similar
      chemical environments hamper their full characterization by X-ray diffraction or
      standard NMR methods. Herein, the successful conformational and interaction
      analysis of a sialylated tetradecasaccharide N-glycan presenting two LacNAc
      repetitions at each arm is presented. This glycan has been identified as the
      receptor of the hemagglutinin protein of pathogenic influenza viruses. To
      accomplish this study, a N-glycan conjugated with a lanthanide binding tag has
      been synthesized, enabling analysis of the system by paramagnetic NMR. Under
      paramagnetic conditions, the NMR signals of each sugar unit in the glycan have
      been determined. Furthermore, a detailed binding epitope of the
      tetradecasaccharide N-glycan in the presence of HK/68 hemagglutinin is described.

PMID- 30238597
TI  - Our Contributions in Synthesis of Diverse Heterocyclic Scaffolds by Using Mixed
      Oxides as Heterogeneous Catalysts.
AB  - This personal account mainly introduces and reviews our recent contributions in
      developing different catalyst materials involving mixed oxides and their scope as
      renewable catalysts in multicomponent reactions to synthesize various novel
      heterocyclic scaffolds under green conditions. The application of various mixed
      oxides and their composites in the organic synthesis is emphasized through this
      review, in order to reveal the versatility, scope and importance of mixed oxides
      and their interactions during the reaction. We have also briefed the limitations
      of mixed oxides as catalysts, to put forward the broader prospective in the
      field.

PMID- 30238598
TI  - Seasonal aggravation of acne in summers and the effect of temperature and
      humidity in a study in a tropical setting.
AB  - BACKGROUND: Effect of seasonality on acne and acne flare has varied
      interpretations depending on the geographical area of study. In tropical areas,
      factors like high temperature and humidity may cause acne flares. AIMS: To assess
      the seasonal variation of acne in patients and to correlate it with the monthly
      temperature and humidity over a period of 1 year. METHODS: A cross-sectional
      study of acne patients was conducted for one year. The patient's acne was graded.
      Patients were specifically questioned about aggravation, improvement, or no
      change in their acne with respect to the seasons. The mean temperature and
      humidity of each month in Delhi were compared with grade of acne. This variation
      in acne was correlated with the temperature and humidity. A P-value < 0.05 was
      considered as statistically significant. RESULTS: Out of 171 patients, 82
      (47.95%) patients reported seasonal variation in their acne. Among them, 69
      patients (40.4%) reported aggravation in summer. Eleven (6.42%) and 2 (1.16%)
      patients reported aggravation in winter and rainy season, respectively. The
      aggravation in summer as compared to rainy and winter season was statistically
      significant. The mean temperature and mean humidity significantly varied with
      seasonal aggravation of acne. CONCLUSIONS: Both temperature and humidity have a
      contributing role in pathogenesis of acne and are causes of acne flare. In our
      study, aggravation of acne was more in summer and rainy season.

PMID- 30238599
TI  - Serum irisin: A prognostic marker for severe acne vulgaris.
AB  - BACKGROUND: Acne vulgaris is a common chronic inflammatory skin disease involving
      pilosebaceous units. Adipokines are secreted by adipose tissue and function as
      signaling networks communicating it with different organs. They may have role in
      pathogenesis of acne vulgaris and the associated insulin resistance. Irisin, a
      hormone like myokine, is one of adipokines with anti-inflammatory, anti-oxidant,
      and anti-diabetic effects. AIMS: We aimed at evaluation of serum irisin level in
      patients with acne vulgaris to assess its correlation with disease pathogenesis.
      PATIENTS AND METHODS: Serum irisin level was measured by an ELISA technique in 60
      acne vulgaris patients and 60 apparently healthy controls. Insulin resistance was
      calculated by Homeostasis Model Assessment of Insulin Resistance index. RESULTS:
      Serum irisin level was significantly lower in acne vulgaris patients than control
      group (P < 0.001). It showed a significant negative correlation with insulin
      resistance among patients (P 0.012). Moreover, it was decreasing significantly
      with the increase in disease severity (P 0.004). CONCLUSIONS: Our results
      revealed that lower serum irisin not only to be a biomarker of disease
      pathogenesis but also to be a potential prognostic predictor for severity in acne
      vulgaris.

PMID- 30238600
TI  - Cancer stem cell populations in lymphoma in dogs and impact of cytotoxic
      chemotherapy.
AB  - Cancer relapse following chemotherapy has been attributed in part to the presence
      of cancer stem cells (CSC), which drive tumour growth and metastasis and are
      highly resistant to the effects of cytotoxic chemotherapy. As a result, treatment
      with cytotoxic chemotherapy selects for drug-resistant CSC populations that
      eventually drive tumour recurrence. Little is known currently regarding the role
      of CSC in dogs with lymphoma, nor the impact of chemotherapy on CSC populations.
      Therefore, we prospectively quantitated CSC populations in dogs with B-cell (BCL)
      and T-cell lymphoma (TCL), using tumour aspirates and flow cytometric analysis
      with a panel of CSC markers. In addition, in vitro studies were carried out to
      determine the impact of chemotherapy resistance on the stem cell phenotype and
      stem cell properties of lymphoma cells. We found that the percentages of tumour
      cells expressing CSC markers were significantly increased in dogs with BCL,
      compared with B cells from normal lymph nodes. Similar findings were observed in
      dogs with TCL. In vitro studies revealed that lymphoma cells selected for
      resistance to CHOP chemotherapy had significantly upregulated expression of CSC
      markers, formed spheroids in culture more readily, and expressed significantly
      greater aldehyde dehydrogenase activity compared with chemotherapy-sensitive
      tumour cells. Similar results were observed in tumour samples dogs with relapsed
      BCL. These findings suggest that cytotoxic chemotherapy can lead to a relative
      enrichment of tumour cells with CSC properties, which may be associated with
      lymphoma recurrence.

PMID- 30238601
TI  - Mechanistic insights into N-Bromosuccinimide-promoted synthesis of imidazo[1,2
      a]pyridine in water: Reactivity mediated by substrates and solvent.
AB  - The mechanism of N-Bromosuccinimide (NBS) promoted synthesis of imidazo[1,2
      a]pyridine in water as well as the effective activation modes of NBS was
      investigated by Density Functional Theory (DFT) calculations. Two main mechanisms
      that differ in the reaction sequence of substrate were explored: styrene with NBS
      then followed by 2-aminopyridine (M1) or simultaneously with NBS and 2
      aminopyridine (M2), and water-assisted M2 is the more favored one. We found that
      the adding sequence of 2-aminopyridine affects profoundly on the title reaction.
      Moreover, upon the assistance of water and NBS, the preferential mechanistic
      scenario involves three major processes: nucleophilic addition, stepwise H-shift
      and intramolecular cyclization, three-step deprotonation, rather than a classical
      bromonium ion species. Specifically, the cooperative interaction of NBS and water
      plays a critical role in the title reaction. Water acts as solvent, reactant,
      anchoring, stabilizer, and catalyst. NBS promotes the above three processes by
      the effective forms of Br+ /Br- , succinimide, and its ethanol isomer.
      Furthermore, noncovalent interactions between catalysts and substrates are
      responsible for the different reactive activities of M1 and M2. Our results
      indicate that simultaneous adding of all reactants is recommended toward
      economical synthesis. (c) 2018 Wiley Periodicals, Inc.

PMID- 30238602
TI  - Novel CNS malformations and skeletal anomalies in a patient with Beaulieu-boycott
      Innes syndrome.
AB  - THO/TREX (transcription/export) is a conserved eukaryotic complex that plays a
      crucial role in gene expression and prevents DNA damage during mitosis and
      meiosis. In mammals, TREX is essential during embryogenesis, determining stem
      cell fate specification by regulating posttranscriptional self-renewal and
      differentiation in several tissues. It is composed of a core called THO,
      consisting of THOC1, 2, 5, 6, 7, and additional proteins. Bi-allelic mutations in
      THOC6 have been associated to Beaulieu-Boycott-Innes syndrome (BBIS), a syndromic
      form of intellectual disability (ID). To date, nine patients harbouring
      homozygous or compound heterozygous mutations in THOC6 have been reported.
      Despite the clinical heterogenity and subtle dysmorphic features in some
      individuals, distinctive facial features are tall forehead, short and upslanting
      palpebral fissures, deep set eyes, flat philtrum, and malocclusion. Nonlife
      threatening congenital anomalies are common, including cardiac and renal
      malformations, anteriorly displaced anus, cryptorchidism in males, submucous
      cleft palate, and corpus callosum dysgenesis. Affected patients usually have
      short stature, mild microcephaly, and mild to moderate ID. Here, we describe an
      Italian patient with BBIS, carrying two compound heterozygous loss-of-function
      (LoF) variants in THOC6 (c.577C > T, p.R193* and c.792_793delCA, p.V264Vfs*48).
      In addition to the common phenotype, she displays cerebellar hypoplasia with
      severe vermian dysgenesis and hydrocephalus due to aqueductal stenosis, multiple
      skeletal anomalies and hypergonadotropic hypogonadism. Thus, we review the
      previous cases and discuss the phenotypic spectrum of BBIS, providing further
      evidence regarding the pivotal role of TREX complex in human development.

PMID- 30238603
TI  - Ultrahigh-Capacity and Long-Life Lithium-Metal Batteries Enabled by Engineering
      Carbon Nanofiber-Stabilized Graphene Aerogel Film Host.
AB  - A safe, high-capacity, and long-life Li metal anode is highly desired due to
      recent developments in high-energy-density Li-metal batteries. However, there are
      still rigorous challenges associated with the undesirable formation of Li
      dendrites, lack of suitable host materials, and unstable chemical interfaces.
      Herein, a carbon nanofiber-stabilized graphene aerogel film (G-CNF film),
      inspired by constructional engineering, is constructed. As the host material for
      Li deposition, the G-CNF film features a large surface area, porous structure,
      and a robust skeleton that can render low local current density. This allows for
      dendrite-free Li deposition and mitigation of problems associated with large
      volume change. Importantly, the G-CNF film can keep high Li plating/stripping
      efficiency at nearly 99% for over 700 h with an areal capacity of 10 mA h cm-2
      (the specific capacity up to 2588 mA h g-1 based on the total mass of carbon host
      and Li metal). The symmetric cells can stably run for more than 1000 h with low
      voltage hysteresis. The full cell with the LiFePO4 cathode also delivers enhanced
      capacity and lowered overpotential. As two-in-one host materials for both
      cathodes and anodes in Li-O2 batteries, the battery exhibits a capacity of 1.2 mA
      h cm-2 .

PMID- 30238604
TI  - Abstracts of the Irish Society of Urology, Annual Meeting, 21-22 September 2018,
      Abbey Hotel, Roscommon, Ireland.

PMID- 30238605
TI  - Programme.

PMID- 30238606
TI  - Coupling of CE-MS for protein and peptide analysis.
AB  - The review is focused on the latest developments in the analysis of proteins and
      peptides by capillary electrophoresis techniques coupled to mass spectrometry.
      First, the methodology and instrumentation are overviewed. In this section,
      recent progress in capillary electrophoresis with mass spectrometry interfaces
      and capillary electrophoresis with matrix-assisted laser desorption/ionization is
      mentioned, as well as separation tasks. The second part is devoted to
      applications-mainly bottom-up and top-down proteomics. It is obvious that
      capillary electrophoresis with mass spectrometry methods are well suited for
      peptide and protein analysis (proteomic research) and it is described how these
      techniques are complementary and not competitive with the often used liquid
      chromatography with mass spectrometry methods.

PMID- 30238607
TI  - Measurements of self-efficacy in musculoskeletal rehabilitation: A systematic
      review.
AB  - OBJECTIVES: Low self-efficacy is a barrier to rehabilitation adherence. Before an
      intervention can be implemented to improve self-efficacy, assessment is required.
      It is currently unknown if a standard measure of self-efficacy has been used to
      assess this in patients with musculoskeletal conditions, specifically for home
      exercise programmes (HEPs). The aim of the present study was to determine which
      self-efficacy scales are being used in conjunction with exercise adherence,
      identify if any scale has been developed to evaluate self-efficacy for HEPs and
      evaluate their psychometric properties. METHODS: Data sources included CINAHL,
      MEDLINE, Pubmed, PsycInfo, and Sport Discus. Studies had to include patients
      suffering from a musculoskeletal injury, pain or disorder; a measure of
      rehabilitation adherence; and patient's self-efficacy. The study population, self
      efficacy measurement used, study quality as identified with the Modified Downs
      and Black checklist, results pertaining to self-efficacy, and level of evidence
      were extracted. The Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines were followed and 29 articles were included.
      RESULTS: A total of 14 scales assessing self-efficacy were identified but no
      scale to assess self-efficacy for HEPs was found. Many scales report internal
      consistency but lack test-retest reliability and validity. CONCLUSIONS: The
      scales identified were specific to condition or tasks, and not applicable for all
      musculoskeletal patient populations. It is important, both for use in the clinic
      and for research, that outcome measures used are reliable and valid.
      Unfortunately, no scale was found to assess self-efficacy for HEPs, which is
      problematic as self-efficacy is task specific. As HEPs are essential to
      rehabilitation, there should be a scale designed specifically to assess self
      efficacy for this task.

PMID- 30238608
TI  - Origin of the Chemiresistive Response of Ultrathin Films of Conductive Metal
      Organic Frameworks.
AB  - Conductive metal-organic frameworks are opening new perspectives for the use of
      these porous materials for applications traditionally limited to more classical
      inorganic materials, such as their integration into electronic devices. This has
      enabled the development of chemiresistive sensors capable of transducing the
      presence of specific guests into an electrical response with good selectivity and
      sensitivity. By combining experimental data with computational modelling, a
      possible origin for the underlying mechanism of this phenomenon in ultrathin
      films (ca. 30 nm) of Cu-CAT-1 is described.

PMID- 30238609
TI  - German Diabetes Study - Baseline data of retinal layer thickness measured by SD
      OCT in early diabetes mellitus.
AB  - PURPOSE: Recent studies highlighted that early diabetic neurodegeneration is
      present before microvascular changes are visible. Retinal neurodegeneration can
      decrease retinal layer thickness. We aimed to determine whether decreased retinal
      layer thickness is present already in the early time course of disease. METHODS:
      A cross-sectional analysis of patients and healthy adults from the German
      Diabetes Study (GDS, ClinicalTrials.gov Identifier number: CT01055093,
      https://clinicaltrials.gov/ct2/show/NCT01055093). Inclusion criteria were a
      diagnosis of diabetes mellitus (DM) within the last 12 months. Retinal layers
      thickness in the nasal pericentral segment was measured by spectral domain ocular
      coherence tomography (SD-OCT). For statistical analysis proc mixed (sas-version
      9.4) was used. RESULTS: One hundred and seventy-eight eyes of 89 patients with
      type 1 DM (58 males, age 36 +/- 11 years, BMI 25.5 +/- 4.2 kg/m2) and 242 eyes of
      121 patients with type 2 DM (84 males, age 53 +/- 10 years, BMI 31.9 +/- 6.3
      kg/m2) with a disease duration of less than 1 year were compared to 76 eyes of 38
      controls (27 males, age 41 +/- 16 years, BMI 27.3 +/- 6.4 kg/m2). Analysis of
      retinal layer thickness and visual function did not reveal a significant
      difference between patients and controls. CONCLUSION: In the early course of DM
      potential, neurodegeneration does not relate to measureable changes of retinal
      layer thickness.

PMID- 30238610
TI  - Associations of maternal and fetal vitamin D status with childhood body
      composition and cardiovascular risk factors.
AB  - Maternal vitamin D deficiency during pregnancy may have persistent adverse
      effects on childhood growth and development. We examined whether 25
      hydroxyvitamin D (25(OH)D) concentrations during pregnancy and at cord blood were
      associated with childhood body composition and cardiovascular outcomes. This
      study was embedded in a population-based prospective cohort in Rotterdam, The
      Netherlands, among 4,903 mothers and their offspring. We measured 25(OH)D
      concentrations at a median gestational age of 20.4 weeks (95% range 18.5-23.4
      weeks) and at birth (40.1 weeks [95% range 35.8-42.3 weeks]). 25(OH)D
      concentrations were categorized into severely deficient (<25.0 nmol/L); deficient
      (25.0 to 49.9 nmol/L); sufficient (50.0 to 74.9 nmol/L) and optimal (>=75.0
      nmol/L). At 6 years, we measured childhood body mass index; fat and lean mass by
      Dual-energy X-ray Absorptiometry; blood pressure; and serum cholesterol,
      triglycerides, and insulin concentrations. Compared with children from mothers
      with optimal 25(OH)D concentrations (>=75.0 nmol/L), those of severely deficient
      vitamin D (<25.0 nmol/L) mothers had a 0.12 standard deviation score (SDS); (95%
      Confidence Interval (CI) [0.03, 0.21]) higher fat mass percentage and a 0.13 SDS
      (95% CI [-0.22, -0.04]) lower lean mass percentage. These associations remained
      after adjustment for current child vitamin D status. Maternal and cord blood
      25(OH)D concentrations were not associated with cardiovascular risk factors in
      childhood. In conclusion, severe maternal 25(OH)D deficiency (<25.0 nmol/L)
      during pregnancy is associated with an adverse childhood body composition
      profile, but we did not observe evidence for an association with childhood
      cardiovascular risk factors. Further studies are needed to replicate our
      findings, to examine the underlying mechanisms, the causality of the
      associations, and the potential for public health interventions.

PMID- 30238611
TI  - Tannic Acid Cross-linked Polysaccharide-Based Multifunctional Hemostatic
      Microparticles for the Regulation of Rapid Wound Healing.
AB  - Hemostatic microparticles (HMs) have been widely used in surgery. To improve the
      comprehensive performance of HMs, multifunctional HMs named HM15 and HM15 ' are
      prepared from starch, carboxymethyl chitosan, hyaluronic acid, and tannic acid.
      Herein, tannic acid is used as an effective cross-linker. A 3D network structure
      for cell growth and wound repair can be formed by secondary cross-linking.
      Through synergistic effect of these natural materials, the process of wound
      healing can be regulated controllably. HM15 and HM15 ' have the ability of rapid
      hemostasis. Moreover, HM15 ' shows excellent properties in antibacteria and wound
      healing acceleration. Blood clotting time treated with different HMs is shortened
      obviously from 436.8 s to 126 s. Compared with Celox, HM15 and HM15 ' exhibited
      better broad spectrum antibacterial activity against both Escherichia coli and
      Staphylococcus aureus. Notably, the wound can be repaired rapidly by HM15 ' in 14
      days. These multifunctional HMs might have an important prospect in clinical
      application.

PMID- 30238612
TI  - Long term follow-up of titanium implants installed in block-grafted areas: A
      systematic review.
AB  - BACKGROUND: An enduring clinical question concerns the outcome (ie, success) of
      implants placed in areas grafted with block-grafts. OBJECTIVE: To undertake a
      systematic review of the literature on the long term results (>=5 years) of
      implants placed in maxillofacial areas grafted with any type of osseous block
      grafts in two-stage surgeries. Further, the review addresses how available
      success criteria were used within the studies. MATERIALS AND METHODS: The MEDLINE
      (PubMed) and EMBASE bibliographic databases were searched up to March 2017 for
      studies evaluating the long term results of implants placed in grafted areas. The
      search strategy was restricted to English language publications using combined
      terms which referred to the treatment method (implants placed in areas grafted
      with bone blocks), and follow-up characteristics (>=5 years and assessment of at
      least one parameter related to implant success criteria). To qualify for
      inclusion, studies should present outcome measurements indicating the success (or
      at least the survival) of the implants. RESULTS: The search strategy yielded 17
      studies, which were included in this systematic review. These studies presented
      survival rates ranging from 88.7% (after 15 years follow-up) to 98.7% (after 5
      years follow-up). Five studies presented data based on predefined success
      criteria with success rates ranging from 86.8% to 100%. In these studies, the
      term "success" was often not properly defined. CONCLUSION: The long term survival
      (>=5 years) of implants placed into block-grafted areas in two-stage surgeries
      was not lower than 75%, while success rates ranged from 86.8% to 100%. Although
      it was possible to identify published success criteria for implant follow-up,
      there is no broad consensus on how to report implant success in a consistent
      manner.

PMID- 30238613
TI  - Unexpected Structure of a Helical N4 -Schiff-Base Zn(II) Complex and Its
      Demetallation: Experimental and Theoretical Studies.
AB  - A new Zn-N4 -Schiff base L=((+/-)-trans-N,N'-Bis(2-aminobenzylidene)-1,2
      diaminocyclohexane) complex was synthesized and fully characterized, showing an
      unexpected self-assembled double-stranded helicate structure. The X-ray crystal
      analysis of the Zn2 L2 complex ((C40 H44 N8 Zn2 ,CH2 Cl2 , a=14.2375(3) A,
      b=16.7976(4) A, c=16.1613(4) A, monoclinic, P21 /n, Z=4) shows a
      centrosymmetrical structure in which zinc atoms are in distorted tetrahedral
      environments, revealing an M- (R, R) left-handed helicity in its asymmetric unit.
      However, it was observed that this dinuclear complex is thermodynamically
      unstable in the presence of small water amounts and undergoes demetallation into
      free N4-Schiff base ligand and ZnO nanoparticles. This hydrolysis process was
      thoroughly identified and monitored through detailed 1 H NMR, DOSY NMR analysis.
      The reaction mechanism of this demetallation event was elucidated by using the
      DFT method, involving an activation energy smaller than 13 kcal/mol. Besides, a
      theoretical mechanism of the demetallation process is given for the first time.

PMID- 30238614
TI  - Validation of the diagnosis of necrotising enterocolitis in a Swedish population
      based observational study.
AB  - AIM: The definition of necrotising enterocolitis (NEC) is based on clinical and
      radiological signs that can be difficult to interpret. The aim of the present
      study was to validate the incidence of NEC in the Extremely Preterm Infants in
      Sweden Study (EXPRESS) METHODS: The EXPRESS study consisted of all 707 infants
      born before 27 + 0 gestational weeks during the years 2004-2007 in Sweden. Of
      these infants, 38 were recorded as having NEC of Bell stage II or higher.
      Hospital records were obtained for these infants. Furthermore, to identify missed
      cases, all infants with a sudden reduction of enteral nutrition, in the EXPRESS
      study were identified (n = 71). Hospital records for these infants were obtained.
      Thus, 108 hospital records were obtained and scored independently by two
      neonatologists for NEC. RESULTS: Of 38 NEC cases in the EXPRESS study, 26 were
      classified as NEC after validation. Four cases not recorded in the EXPRESS study
      were found. The incidence of NEC decreased from 6.3% to 4.3%. CONCLUSION:
      Validation of the incidence of NEC revealed over- and underestimation of NEC in
      the EXPRESS study despite carefully collected data. Similar problems may occur in
      other national data sets or quality registers.

PMID- 30238616
TI  - Drugs don't work in patients who don't take them.

PMID- 30238615
TI  - Sensitivity of Antibacterial Activity to Backbone Sequence in Constitutionally
      Isomeric OligoTEAs.
AB  - Antimicrobial peptides are promising alternatives to traditional antibiotics but
      their translational potential is limited due to rapid degradation by serum
      proteases. Recently, a number of peptidomimetics with backbones resistant to
      proteolysis have been synthesized and their antimicrobial potential evaluated as
      a function of their hydrophobic to cationic ratio. However, these mimetics also
      have a fixed backbone thus making it difficult to isolate the effect of backbone
      hydrophobic composition and sequence. In this work, advantage is taken of the
      oligothioetheramide (oligoTEA) synthetic strategy that allows for precise control
      over backbone and pendant group placement to systematically study the effect of
      backbone hydrophobic sequence while keeping pendant group constant. Biophysical
      data acquired with a set of constitutional oligoTEA isomers show that backbone
      hydrophobic sequence, that is, local hydrophobicity, affects the mode of oligoTEA
      interaction with lipid bilayers. This differential interaction among the
      constitutionally isomeric oligoTEAs is manifested in their antibacterial
      activities and points to the possibility of using backbone hydrophobic sequence
      to tune antibacterial potency and selectivity.

PMID- 30238618
TI  - Kerry Vincent Casey (1934-2018).

PMID- 30238617
TI  - New frontiers in community initiatives to increase vegetable consumption.
AB  - ISSUE ADDRESSED: Public health concerns about insufficient consumption of
      vegetables across all demographics in Australia have led to 20 years of behaviour
      change interventions ranging from social marketing to interactive small group
      programs, with modest results. To maximise health promotion intervention
      outcomes, practitioners need up-to-date information that helps them navigate the
      complexity of food systems and eating behaviours. METHODS: This scoping review of
      Australian and international research, including peer-reviewed and grey
      literature, provides a picture of health promotion nutrition interventions, as
      well as other initiatives that may promote increased vegetable consumption.
      Search terms related to nutrition and vegetable consumption, type of intervention
      or initiative, for example, campaign; and consumer values and behaviour. A wide
      range of data sources were used including scholarly papers, market research
      reports and publicly available websites of community organisations (eg, OOOOBY).
      A broad food systems typology was developed to provide a framework for the
      review. RESULTS: The review finds an emerging group of community-driven
      initiatives within local food systems that appear to have positive impacts on
      vegetable consumption. These initiatives sit within a multi-faceted approach to
      health and well-being that is consistent with the tenets of the Ottawa Charter
      for Health Promotion, including community engagement, social justice and
      sustainability goals. CONCLUSIONS: More research into the impact of these new
      frontiers is needed, but our preliminary findings point to the potential for
      health promotion practitioners to collaborate on local/community food system
      initiatives that are not motivated primarily by health goals, but have the
      potential to deliver multiple health and environmental outcomes. SO WHAT?: This
      review demonstrated community-driven initiatives around local food systems show
      the most promise in promoting vegetable consumption and addressing the
      determinants of health. Health promotion efforts to encourage food security and
      healthy eating could be strengthened through collaborations within these new
      frontiers.

PMID- 30238619
TI  - Efficacy of collagen matrix implant on adhesions in restrictive strabismus: An
      experimental study in a rabbit model.
AB  - PURPOSE: To determine the efficacy of a biodegradable collagen matrix implant
      (Ologen, Aeon Astron Europe BV, Leiden, the Netherlands) in reducing adhesions in
      a rabbit model of restrictive strabismus. METHODS: A prospective, masked
      observer, controlled experimental study was performed. Sixty superior rectus
      muscles of 30 rabbits were resected and Marlex mesh was fixed beneath the
      resected muscle using nonabsorbable suture. Forty eyes underwent one of two
      different procedures; the resected muscle was wrapped with preserved human
      amniotic membrane (AM group) or Ologen (Ologen group). Randomly selected 20 eyes
      served as controls. Eyes were enucleated at 4 weeks after surgery to measure the
      severity of adhesion using a push pull gauge. Histopathological examination was
      performed. RESULTS: At postoperative week four, the average tensile strength of
      the myoscleral adhesion was significantly lower in the Ologen group (151.8 +/-
      42.7 gram force) compared to controls (347.9 +/- 68.6 gram force) and AM group
      (193.0 +/- 44.3 gram force) (p < 0.001 and p = 0.045, respectively). Ologen group
      showed significantly lower degree of acute inflammation, chronic inflammation and
      rectus muscle fibrosis compared with controls (all p < 0.01). The degree of
      chronic inflammation was significantly lower in the Ologen group compared with AM
      group (p = 0.012). CONCLUSION: Compared to amniotic membrane, Ologen is more
      effective in reducing mesh-related extraocular muscle adhesions in a rabbit model
      of restrictive strabismus.

PMID- 30238620
TI  - Assessment of CYP-Mediated Drug Interactions for Evocalcet, a New Calcimimetic
      Agent, Based on In Vitro Investigations and a Cocktail Study in Humans.
AB  - Evocalcet is a novel calcimimetic agent for the treatment of secondary
      hyperparathyroidism (SHPT). This study evaluated the effects of evocalcet on
      inhibition and induction of cytochrome P450 (CYP) isozymes. Although drug
      interactions arising from reversible inhibition of CYP isozymes by evocalcet were
      considered unlikely based on the results of in vitro studies and static model
      analyses, the potential for evocalcet to cause time-dependent inhibition of CYP3A
      or induction of several CYP isozymes could not be ruled out. Therefore, a
      clinical drug-drug interaction (DDI) study to evaluate the effects of evocalcet
      on the pharmacokinetics (PKs) of probe substrates for CYP isozymes (CYP1A2,
      CYP2B6, CYP2C8, CYP2C9, and CYP3A) was conducted in healthy male volunteers using
      a novel cocktail combination. Evocalcet did not significantly affect the PKs of
      the probe substrates, confirming that CYP-mediated interactions were unlikely.

PMID- 30238621
TI  - Achieving biventricular circulation in patients with moderate hypoplastic right
      ventricle in pulmonary atresia intact ventricular septum after transcatheter
      pulmonary valve perforation.
AB  - OBJECTIVE: Transcatheter valve perforation for pulmonary atresia intact
      ventricular septum is the standard of care for patients with mild right
      ventricular hypoplasia. However, its role in moderate right ventricular
      hypoplasia has been less well defined. We sought to report the long-term outcome
      of patients with moderate hypoplastic right ventricle who had undergone the
      procedure. DESIGN, SETTINGS, AND PATIENTS: We performed a retrospective analysis
      on patients who had undergone transcatheter pulmonary valve perforation from
      January 1996 to January 2015 at our institution. The procedures would be carried
      out irrespective of the right ventricular size, as long as there were no absolute
      contraindications. INTERVENTION AND OUTCOME MEASURES: Demographic and procedural
      data were correlated with outcome measures. Outcomes analyzed included procedural
      success, reintervention rates, final circulation type, and functional class.
      Multivariate analysis and receiver operator curve were used to identify for
      parameters in predicting biventricular circulation. RESULTS: The procedural
      success rate was 92% (33 out of 36) in this group with moderate right ventricular
      hypoplasia (tricuspid valve z score -4.2 +/- 3.0, 69.4% of patients with z score
      <-2.5). Early reintervention rate was 39%, mostly being insertion of modified
      Blalock-Taussig shunt. Overall reintervention-free survival was 53%, 30%, and 19%
      at 1, 6, and 12 months postintervention. Despite no significant catch-up right
      ventricular growth, majority of survivors (84%) enjoyed a biventricular
      circulation with good functional status. A tricuspid to mitral valve ratio >0.79
      was a good predictor of biventricular outcome. (specificity of 100%, positive
      predictive value 100%) CONCLUSION: Encouraging long-term results with
      biventricular circulation and functional status were demonstrated with
      transcatheter pulmonary valve perforation in patients even with moderate
      hypoplastic right ventricle, which is comparable to that with mild right
      ventricular hypertrophy. The baseline tricuspid to mitral valve ratio was
      identified as a potentially useful tool in predicting biventricular circulation.

PMID- 30238622
TI  - Rare manifestation of Neurofibromatosis type 1: A plexiform neurofibroma
      involving the mediastinum and lungs with endobronchial neurofibromata.
AB  - Neurofibromatosis type 1 (NF1) is a multisystem phakomatosis. The intrathoracic
      manifestations of NF1 are protean. We describe a rare case of a plexiform
      neurofibroma infiltrating the mediastinum and lungs with multiple endobronchial
      neurofibromata. To our knowledge, a mediastinal plexiform neurofibroma extending
      into the lungs on CT has not been reported.

PMID- 30238623
TI  - Toward understanding genomic instability, mitochondrial dysfunction and aging.
AB  - The biology of aging is an area of intense research, and many questions remain
      about how and why cell and organismal functions decline over time. In mammalian
      cells, genomic instability and mitochondrial dysfunction are thought to be among
      the primary drivers of cellular aging. This review focuses on the
      interrelationship between genomic instability and mitochondrial dysfunction in
      mammalian cells and its relevance to age-related functional decline at the
      molecular and cellular level. The importance of oxidative stress and key DNA
      damage response pathways in cellular aging is discussed, with a special focus on
      poly (ADP-ribose) polymerase 1, whose persistent activation depletes cellular
      energy reserves, leading to mitochondrial dysfunction, loss of energy
      homeostasis, and altered cellular metabolism. Elucidation of the relationship
      between genomic instability, mitochondrial dysfunction, and the signaling
      pathways that connect these pathways/processes are keys to the future of research
      on human aging. An important component of mitochondrial health preservation is
      mitophagy, and this and other areas that are particularly ripe for future
      investigation will be discussed.

PMID- 30238624
TI  - Cardiac morphology for the millennial cardiology fellow: Nomenclature and
      advances in morphologic imaging.
AB  - Cardiology fellows-in-training, both in adult and pediatric hospitals, need
      structured education in regards to congenital heart disease (CHD) nomenclature.
      With improved survival of patients with CHD, it is not uncommon for these
      patients to seek care in multiple adult and pediatric hospitals. A deep
      understanding of CHD nomenclature would aid in providing accurate medical and
      surgical care for these patients. In this forum, we share our experience with
      such structured education and also comment on recent advances in morphologic
      imaging that would aid in understanding the nomenclature.

PMID- 30238625
TI  - Assessing the variation in workload among general practitioners in urban and
      rural areas: An analysis based on SMS time sampling data.
AB  - OBJECTIVE: An important reason why general practitioners (GPs) are less inclined
      to work in rural areas is a perception of a higher workload. This study assesses
      the differences in the workloads of GPs in rural and urban areas. We used two
      definitions of rurality, one based on the number of addresses per square
      kilometre, and a second defined by the expected decline in population. METHODS:
      We collected time use data over 1 year by sending SMS text messages to Dutch GPs
      who each participated during a period of 1 week. This data was matched with those
      from GPs' registration and practice location. Data from 596 self-employed GPs
      were analysed using descriptive statistics and multiple regression analyses.
      RESULTS: In group practices, the patient list size of rural GPs was, on average,
      231 patients more than those of urban GPs. They worked 3.5 more hours per week,
      with 2.6 more hours directly related to patients. A small significant relation
      was found between degree of urbanisation and the dependent variables list size
      and working hours. Working in a depopulation area had no significant effect on
      the workload indicators. Furthermore, GPs in group practices worked significantly
      fewer hours, and had smaller list sizes, than GPs in single-handed practices.
      CONCLUSION: The results show that the assumption of a higher workload in rural
      practices does not completely match the objective workload of GPs in these areas.
      Rural GPs have a higher workload in certain cases, but the type of a practice
      seems a more important determinant.

PMID- 30238626
TI  - The enzymatic resolution of 1-(4-chlorophenyl)ethylamine by Novozym 435 to
      prepare a novel triazolopyrimidine herbicide.
AB  - The kinetic resolution of (R,S)-1-(4-chlorophenyl)ethylamine was accomplished
      using a commercial lipase from Candida antarctica (Novozym 435). The performance
      of this lipase was investigated for the enantioselective amidation of (R,S)-1-(4
      chlorophenyl)ethylamine, leaving the target product (S)-1-(4
      chlorophenyl)ethylamine in its unreacted form. The effects of various types of
      solvents and an acyl donor, the molar ratio of the substrate to the acyl donor,
      and the reaction temperature were studied. The optimum reaction conditions were
      found to result in amidation with methyl 2-tetrahydrofuroate at 40 degrees C in
      methyl tert-butyl ether, with a substrate/acyl donor molar ratio of 1:2.4. The
      conversion rate of (R,S)-1-(4-chlorophenyl)ethylamine was 52%, with an
      enantiomeric excess of 99% towards the unreacted substrate in a reaction time of
      22 hours. Finally, using optically pure (S)-1-(4-chlorophenyl)ethylamine as the
      raw material, the chemical synthesis of (S)-N-(1-(4-chlorphenyl)ethyl)-2-(5,7
      dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylthio)acetamide, a novel
      triazolopyrimidine herbicide, was achieved, and the total yield and purity were
      83.5% and 95.3%, respectively.

PMID- 30238627
TI  - Echocardiographic parameters associated with biventricular circulation and right
      ventricular growth following right ventricular decompression in patients with
      pulmonary atresia and intact ventricular septum: Results from a multicenter
      study.
AB  - BACKGROUND: In patients with pulmonary atresia, intact ventricular septum
      (PA/IVS) following right ventricular (RV) decompression, RV size and morphology
      drive clinical outcome. Our objectives were to (1) identify baseline and
      postdecompression echocardiographic parameters associated with 2V circulation,
      (2) identify echocardiographic parameters associated with RV growth and (3)
      describe changes in measures of RV size and changes in RV loading conditions.
      METHODS: We performed a retrospective analysis of patients who underwent RV
      decompression for PA/IVS at four centers. We analyzed echocardiograms at
      baseline, postdecompression, and at follow up (closest to 1-year or prior to
      Glenn circulation). RESULTS: Eighty-one patients were included. At last follow
      up, 70 (86%) patients had 2V circulations, 7 (9%) had 1.5 ventricle circulations,
      and 4 (5%) had single ventricle circulations. Follow-up echocardiograms were
      available in 43 (53%) patients. The majority of patients had improved RV systolic
      function, less tricuspid regurgitation (TR), and more left-to-right atrial
      shunting at a median of 350 days after decompression. Multivariable analysis
      demonstrated that larger baseline tricuspid valve (TV) z-score (P = .017), >=
      moderate baseline TR (P = .045) and smaller baseline RV area (P < .001) were
      associated with larger increases in RV area. Baseline RV area >=6 cm2 /m2 had 93%
      sensitivity and 80% specificity for identifying patients who ultimately achieved
      2V circulation. All patients with RV area >=8 cm2 /m2 at follow up achieved 2V
      circulation. This finding was confirmed in a validation cohort from a separate
      center (N = 25). Factors associated with achieving RV area >=8 cm2 /m2 included
      larger TV z-score (P = .004), >= moderate baseline TR (P = .031), and >= moderate
      postdecompression pulmonary regurgitation (P = .002). CONCLUSIONS: Patients with
      PA/IVS and smaller TV annuli are at risk for poor RV growth. Volume-loading
      conditions signal increased capacity for growth sufficient for 2V circulation.

PMID- 30238628
TI  - Fish consumption and risk of depression: Epidemiological evidence from
      prospective studies.
AB  - INTRODUCTION: The evidence on the association of fish or omega-3 fatty acid
      intake with depression is inconsistent. We conducted a systematic review and meta
      analysis of prospective cohort studies to examine this association. METHODS:
      Database searches in PubMed and Web of Science were conducted to identify
      relevant articles published up to April 2018, which were supplemented by hand
      searches of reference lists of the retrieved articles. Using a random-effects
      model, we calculated pooled relative risks (RR) of depression in relation to
      consumption of fish or omega-3 fatty acids after adjusting for potential
      confounders. RESULTS: A total of 10 prospective cohort studies with 6672 cases of
      depression among 109 764 participants were included in the meta-analysis. The
      pooled adjusted RR of depression for the highest vs lowest category of fish
      consumption was 0.89 (95% CI: 0.80-0.99). The pooled adjusted RR of depression
      for the highest vs lowest category of omega-3 intake was 0.87 (95% CI: 0.74
      1.04). In the dose-response analysis, the pooled adjusted RRs for an increment of
      1 serving/week of fish consumption and 500 mg/day of omega-3 fatty acid intake
      were 0.89 (95% CI: 0.75-1.04) and 0.99 (95% CI: 0.94-1.04), respectively. There
      was no evidence of heterogeneity. DISCUSSION: Our findings provide quantitative
      evidence for a modest inverse association between fish or omega-3 fatty acid
      intake and risk of depression, especially in women. These findings from the
      observational studies need to be confirmed through large randomized clinical
      trials of fish consumption or omega-3 fatty acid intake and risk of depression.

PMID- 30238629
TI  - Ventilation perfusion single photon emission computed tomography: Referral
      practices and diagnosis of acute pulmonary embolism in the quaternary clinical
      setting.
AB  - INTRODUCTION: Ventilation perfusion single photon emission computed tomography
      (V/Q SPECT) and CTPA are the two leading imaging studies used to investigate
      acute pulmonary embolism. V/Q SPECT is often the first line investigation for
      pregnant patients and young females. Historically, V/Q Planar studies have high
      rates of indeterminate findings resulting in a preference for CTPA studies. The
      purpose of this research is to examine current V/Q SPECT referral practices in
      the quaternary clinical setting and to confirm V/Q SPECT studies have low rates
      of equivocal findings. METHODS: Retrospective study of a 6-month period of all
      completed V/Q SPECT studies (+/- LDCT) indicated for investigation of acute PE.
      V/Q SPECT studies were reported using the European Association of Nuclear
      Medicine guidelines. Patient demographic data and V/Q SPECT findings were
      recorded. CTPA and Doppler Ultrasound report findings were included if performed
      48 hours prior to, or following V/Q SPECT study. Standard descriptive statistical
      analysis was undertaken. RESULTS: Ninety-nine percent of V/Q SPECT studies had
      reports positive or negative for acute PE, with 1% inconclusive. Twenty-two
      percent of patients had either CTPA or Doppler Ultrasound studies within a 48-
      hour period prior to, or following V/Q SPECT, with the majority having a negative
      Doppler ultrasound prior to negative V/Q SPECT. Sixty-eight percent of patients
      referred for V/Q SPECT were females under the age of 55, 40% of whom were
      pregnant. CONCLUSIONS: Ventilation perfusion single photon emission computed
      tomography has low rates of equivocal findings with referral practices indicating
      pregnant patients and young women are considered to most benefit from V/Q SPECT
      as a first line investigation for acute PE.

PMID- 30238631
TI  - The role of obesity in the fatal outcome of Schaaf-Yang syndrome: Early onset
      morbid obesity in a patient with a MAGEL2 mutation.
AB  - Schaaf-Yang syndrome (SYS) was recently identified as a genetic condition
      resembling Prader-Willi syndrome. It is caused by mutations on the paternal
      allele of the MAGEL2 gene, a gene that has been mapped in the Prader-Willi
      critical region. Here, we present an infant with SYS who sadly died because of
      the combination of hypotonia, sleep apnea, and obesity. A heterozygous premature
      stop mutation in MAGEL2 was identified in the patient. The main factors reported
      in the mortality of SYS are lethal arthrogryposis multiplex congenita, fetal
      akinesia, and pulmonary problems. Our clinical report indicates that obesity and
      its complications are an important additional factor in the mortality associated
      with SYS. Therefore, we advise to strictly monitor weight and intensively treat
      overweight and obesity in SYS.

PMID- 30238630
TI  - Sex differences in adherence to antihypertensive treatment in patients aged above
      55: The French League Against Hypertension Survey (FLAHS).
AB  - Despite the availability of efficient therapies to reduce the risk of
      cardiovascular complications, poor adherence to antihypertensive (anti-HTN) drugs
      is frequent, especially during the first year of treatment and among
      uncontrolled/resistant hypertensive patients. The aim of the study was to
      identify factors associated with adherence to anti-HTN treatment and to examine
      whether they differ across sex. A total of 2743 treated hypertensive participants
      to the cross-sectional Metascope survey (France, 2015) aged 55 years or more were
      included. The authors measured adherence to anti-HTN treatment using the 6-item
      Girerd compliance test. Variations in adherence were examined using the Rao-Scott
      statistics and Poisson regression. Overall, 63.6% of participants were adherent
      to anti-HTN treatment. Adherence was more frequent among women than men (69% vs
      58%, P < 10-4 ). For both sexes, level of adherence was positively associated
      with age (P < 10-4 ), but inversely associated with number of anti-HTN tablets,
      number of tablets taken for metabolic diseases, history of cardiovascular
      diseases, number of other chronic diseases (all P < 10-4 ). The inverse
      relationship between adherence and the number of anti-HTN tablets significantly
      differed between sexes (P < 10-4 ): Adherence decreased sharply when taking two
      or more anti-HTN tablets in men, whereas the decrease in women was only observed
      when taking three or more anti-HTN tablets. This study suggests that adherence to
      anti-HTN treatment is higher among women, decreases with the number of tablets
      prescribed, and differentially so across sex. Reducing the number of tablets for
      anti-HTN treatment may improve adherence, especially among men and patients with
      multiple comorbidities.

PMID- 30238632
TI  - Schlemm's canal measured by optical coherence tomography and correlation study in
      a healthy Caucasian child population.
AB  - PURPOSE: To measure the Schlemm's canal (SC) in vivo by Fourier-domain optical
      coherence tomography (FD-OCT) in a Caucasian paediatric population. METHODS:
      Participants of this cross-sectional study were 290 healthy children. In the
      right eye of each child, SC cross-sectional diameter and area measurements were
      made with the FD-OCT instrument RTVue(r) (Optovue Inc, Fremont, CA, USA) in the
      nasal and temporal quadrants. These SC variables were then assessed for
      correlation with the factors age, gender, refractive error, anterior chamber
      angle and trabecular meshwork (TM) metrics. Finally, the reproducibility of the
      SC measurements was assessed in 30 of the participants. RESULTS: Mean participant
      age was 10.7 +/- 3.4 years (range 3-18). SC diameters could be measured in both
      quadrants in 70.6% and 70.4% of subjects, respectively. Mean SC diameters were
      similar (p = 0.125) for the temporal and nasal quadrants: 266.7 +/- 84.1 MUm
      (range 131-509) and 273.2 +/- 77.3 MUm (range 124-486), respectively. Mean SC
      areas were also similar (p = 0.167) for the two quadrants: 9975 +/- 3514 MUm2
      (range 4000-23 000) versus 9688 +/- 3297 MUm2 (range 3000-24 000). No differences
      were detected in SC measurements according to gender, refractive error or angle
      and TM measurements (R <= 0.116; p >= 0.125). The exception was age which was
      directly correlated with SC size (p <= 0.041). The reproducibility of the SC
      measurements was excellent (intraclass correlation coefficients >=0.936).
      CONCLUSION: FD-OCT allows the identification of the SC in children. Our data
      indicate an increase in SC size produced with age.

PMID- 30238633
TI  - Optical coherence tomography angiography and microvascular changes in diabetic
      retinopathy: a systematic review.
AB  - To use optical coherence tomography angiography (OCTA) to evaluate foveal
      microvascular changes in diabetes by comparing the area of foveal avascular zone
      (FAZ) in healthy controls and patients with diabetes with no diabetic retinopathy
      (NDR) as well as different stages of diabetic retinopathy (DR). A systematic
      literature search was performed based on the population, intervention, comparison
      and outcome (PICO) strategy by two independent reviewers. The search was
      performed in PubMed, Embase and Cochrane Library, including keywords 'diabetes
      mellitus', 'DR' and 'OCTA'. Of 358 studies initially identified, 215 studies were
      screened after duplicate removal. Of these, we included 12 (nine cross-sectional
      and three retrospective) studies in this review. With the data at hand, it was
      not possible to perform a meta-analysis. The selected studies included patients
      with NDR (n = 8), non-proliferative diabetic retinopathy (NPDR, n = 8) and
      proliferative diabetic retinopathy (PDR, n = 6). Several of the studies provided
      information for more than one diabetic group. In general, there was a trend
      towards a larger area of FAZ in patients with diabetes. As compared to healthy
      controls, this was reported in patients with NDR (five of eight studies), NPDR
      (seven of eight studies) and PDR (six of six studies). Optical coherence
      tomography angiography (OCTA) is non-invasively able to identify foveal capillary
      non-perfusion as an early event in DR. In some studies, this has even been
      identified in patients without clinically identifiable microvascular lesions.
      Longitudinal studies would be needed to examine if OCTA-findings are able to
      predict long-term structural and functional outcome.

PMID- 30238634
TI  - Knowledge and practices regarding Middle East Respiratory Syndrome Coronavirus
      among camel handlers in a Slaughterhouse, Kenya, 2015.
AB  - Dromedary camels are implicated as reservoirs for the zoonotic transmission of
      Middle East Respiratory Syndrome coronavirus (MERS-CoV) with the respiratory
      route thought to be the main mode of transmission. Knowledge and practices
      regarding MERS among herders, traders and slaughterhouse workers were assessed at
      Athi-River slaughterhouse, Kenya. Questionnaires were administered, and a check
      list was used to collect information on hygiene practices among slaughterhouse
      workers. Of 22 persons, all washed hands after handling camels, 82% wore
      gumboots, and 65% wore overalls/dustcoats. None of the workers wore gloves or
      facemasks during slaughter processes. Fourteen percent reported drinking raw
      camel milk; 90% were aware of zoonotic diseases with most reporting common ways
      of transmission as: eating improperly cooked meat (90%), drinking raw milk (68%)
      and slaughter processes (50%). Sixteen (73%) were unaware of MERS-CoV. Use of
      personal protective clothing to prevent direct contact with discharges and
      aerosols was lacking. Although few people working with camels were interviewed,
      those met at this centralized slaughterhouse lacked knowledge about MERS-CoV but
      were aware of zoonotic diseases and their transmission. These findings highlight
      need to disseminate information about MERS-CoV and enhance hygiene and biosafety
      practices among camel slaughterhouse workers to reduce opportunities for
      potential virus transmission.

PMID- 30238635
TI  - Semi-quantitative determination of designer steroids by high-performance liquid
      chromatography with ultraviolet detection in the absence of reference material.
AB  - New designer steroids are continually being encountered in dietary supplements
      that claim to increase muscle mass, but quantitative analysis of such ingredients
      is challenging due to the availability, quality, or cost of commercial reference
      materials. Although standard reference material typically becomes available for
      these emerging compounds, laboratories often face the challenge of finding
      properly certified materials from accredited suppliers, due to traceability
      requirements. Several of these designer steroids have been isolated and
      identified using multiple structural elucidation tools. Structural
      characteristics of these compounds of interest were evaluated and molar
      absorptivity data was collected and compared to several readily available steroid
      standards using ultraviolet/visible spectroscopy. This approach was used to find
      suitable compounds for use as surrogate reference materials in the semi
      quantitative determination of two designer steroids, 1-dehydroepiandrosterone (1
      androsterone) and 6beta-chloro-4-androsten-17beta-ol-3-one (6beta
      chlorotestosterone). Laboratory-fortified matrix samples and dietary supplement
      samples were analyzed using this method for the estimation of 1-androsterone and
      6beta-chlorotestosterone by HPLC-UV. Assay values obtained for the estimation of
      1-androsterone in a dietary supplement sample using a prasterone or
      dehydroepiandrosterone (DHEA) standard curve were 100% of those obtained using a
      1-androsterone reference standard, once it became commercially available.
      Estimations for 6beta-chlorotestosterone in laboratory-fortified matrix samples
      using a testosterone standard curve were 92%-93% of those obtained using isolated
      6beta-chlorotestosterone as "reference material."

PMID- 30238636
TI  - Gastric administration of garlic powder containing the trpa1- agonist allicin
      induces specific epigastric symptoms and gastric relaxation in healthy subjects.
AB  - BACKGROUND: TRPA1 is an excitatory ion channel and is involved in sensory
      processes including thermal nociception and inflammatory pain. The allicin in
      garlic is a strong activator of the TRPA1 channel. AIM: To evaluate the effect of
      intragastric garlic powder containing allicin on perception, gastric tone, and
      mechanosensitivity. METHODS: An infusion-barostat balloon assembly was used for
      infusion of test solutions, for distension, and to measure proximal gastric
      compliance and tone. After an initial open label dose finding with 1 g, 2 g, 3.75
      g, and 7.5 g commercially available garlic powder, a bolus of 2 g garlic powder
      (11 mg allicin)/60 mL H2 O was considered to induce moderate but constant
      sensation and was used hereafter in a placebo-controlled, single-dose, double
      blind, randomized study in 7 volunteers to evaluate gastric sensation, tone, and
      mechanosensitivity. KEY RESULTS: Bolus injection of garlic caused immediate
      epigastric symptoms, mean aggregate symptom scores (AUC in 15 minutes) were 106
      +/- 49 vs. 35 +/- 30 after placebo (P = 0.01). Garlic induced significant
      epigastric pressure, stinging, and warmth (P < 0.01 vs. placebo), while intensity
      of cramps, satiety, nausea, and pain was not significantly different to placebo
      (P > 0.05). Garlic induced an immediate, short lived fundic relaxation (balloon
      volume 627 +/- 349 mL vs. -145 +/- 120 mL; P < 0.02). No effect of allicin on
      proximal gastric mechanosensitivity and compliance was observed (NS). CONCLUSION
      AND INFERENCES: Garlic containing allicin induces immediate epigastric symptoms
      of pressure, stinging, and warmth and induces fundic relaxation but does not
      influence mechanosensitivity or compliance. TRPA1 is a receptor that is involved
      in gastric sensation and motility.

PMID- 30238637
TI  - The Biomedical Use of Silk: Past, Present, Future.
AB  - Humans have long appreciated silk for its lustrous appeal and remarkable physical
      properties, yet as the mysteries of silk are unraveled, it becomes clear that
      this outstanding biopolymer is more than a high-tech fiber. This progress report
      provides a critical but detailed insight into the biomedical use of silk. This
      journey begins with a historical perspective of silk and its uses, including the
      long-standing desire to reverse engineer silk. Selected silk structure-function
      relationships are then examined to appreciate past and current silk challenges.
      From this, biocompatibility and biodegradation are reviewed with a specific focus
      of silk performance in humans. The current clinical uses of silk (e.g., sutures,
      surgical meshes, and fabrics) are discussed, as well as clinical trials (e.g.,
      wound healing, tissue engineering) and emerging biomedical applications of silk
      across selected formats, such as silk solution, films, scaffolds, electrospun
      materials, hydrogels, and particles. The journey finishes with a look at the
      roadmap of next-generation recombinant silks, especially the development pipeline
      of this new industry for clinical use.

PMID- 30238638
TI  - Identification of the anabolic steroid 6beta-chlorotestosterone in a dietary
      supplement.
AB  - Capsules that were labeled to be performance-enhancing dietary supplements
      obtained during an investigation were found to contain an unrecognized steroid
      like substance. This compound was isolated by liquid chromatography (LC) fraction
      collection and characterized using several qualitative analytical techniques,
      including ultraviolet (UV) spectroscopy, gas chromatography-mass spectrometry (GC
      MS), liquid chromatography-high resolution accurate mass-mass spectrometry (LC
      HRAM-MS), as well as 1 H, 13 C, and two-dimensional nuclear magnetic resonance
      (NMR) spectrometry. This multi-technique analytical approach was used to identify
      the designer steroid as 6beta-chloro-4-androsten-17beta-ol-3-one (6beta
      chlorotestosterone), an analog of testosterone about which little has been
      published.

PMID- 30238639
TI  - Determination of Thirteen Trace and Toxic Elements in Urine Using Inductively
      Coupled Mass Spectrometry.
AB  - We developed and validated a method for the assessment of thirteen separate trace
      and toxic elements using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).
      Included elements were as follows: aluminum, chromium, manganese, iron, cobalt,
      nickel, copper, zinc, arsenic, molybdenum, cadmium, tungsten, and lead. The
      measurements of all elements in urine samples were conducted using ICAP-Q ICP-MS
      in a single method. The performance characteristics of the assay were determined
      according to clinical laboratory standards. The assay was linear in the
      concentration range of 1.0 to 1000.0 ug/liter for all elements. The method was
      precise and accurate with limits of quantitation of 1 ug/liter for chromium,
      manganese, cobalt, nickel, copper, cadmium, tungsten, and lead; 2 ug/liter for
      iron and arsenic; 5 ug/liter for aluminum; and 50 ug/liter for zinc. This method
      has successfully been used for the assessment of all thirteen elements included
      in urine and has been shown to be effective as a simple, precise, and sensitive
      analytical technique for biological monitoring of urine samples. (c) 2018 by John
      Wiley & Sons, Inc.

PMID- 30238640
TI  - Proximity Ligation Assay (PLA).
AB  - Proximity ligation assay (PLA), also referred to as Duolink(r) PLA technology,
      permits detection of protein-protein interactions in situ (at distances <40 nm)
      at endogenous protein levels. It exploits specific antibodies identifying (either
      directly or indirectly) the two proteins of interest and utilizes specific DNA
      primers covalently linked to the antibodies. A hybridization step followed by DNA
      amplification with fluorescent probes permit visualization of spots of proximity
      by fluorescence microscopy. Since the development of PLA in 2002, it has been
      increasingly used to detect the interaction between two proteins with high
      sensitivity and specificity. It is a simple and sensitive technique to study
      protein-protein interaction in cells. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30238641
TI  - Osmoregulatory function of betaine in alleviating heat stress in poultry.
AB  - This review focuses on the osmoregulatory function of betaine and its effect in
      terms of alleviating heat stress in poultry. Poultry appear to be particularly
      sensitive to temperature-associated environmental challenges, especially heat
      stress. High ambient temperatures are deleterious to productive performance in
      poultry, including broilers, laying hens, quails and turkeys, resulting in
      considerable economic losses. Heat stress impairs overall poultry production by
      decreasing feed intake and negatively affecting intestinal development, leading
      to reduced nutrient digestibility. Apart from inducing a high mortality rate,
      heat stress is known to depress growth rate and reduce meat yield in broilers. In
      layers, lower feed intake impairs ovarian function, leading to decreased feed
      efficiency, egg production and egg quality. In addition, reduced immune
      functions, such as thyroid activity and antibody production, are evident in
      poultry exposed to heat stress. Heat stress increases the production of oxidants,
      causing oxidative stress and lipid peroxidation of cell membranes. Poultry
      respond physiologically and behaviourally when encountering the negative effects
      of heat stress, attempting to return the body to homeostasis. This requires
      energy at the expense of weight gain or egg production. Due to its zwitterionic
      structure, betaine has osmoprotective properties that aid in protecting
      intestinal cell proteins and enzymes from environmental stress, including high
      ambient temperature, thereby counteracting performance losses. Betaine also
      exerts an osmoregulatory role in cells, regulating water balance, and this
      results in more stable tissue metabolism. Inclusion of betaine in the diet may be
      beneficial for alleviating physical reactions to heat stress, as indicated by
      increases in nutrient digestibility. In broilers, betaine supplementation
      increases weight gain and breast muscle yield, while improving feed conversion.
      In layers, betaine supplementation improves egg production, egg quality traits
      and immune indices. In conclusion, due to its osmoregulatory functions, betaine
      plays an important role in alleviating heat stress in poultry.

PMID- 30238642
TI  - Beyond Common Metal-Metal Bonds, kappa3 -Bis(donor)ferrocenyl->Transition-Metal
      Interactions.
AB  - Ligands with 1,1'-bis(donor)ferrocene motif are capable of a wide range of
      binding modes, including the trans chelation mode in which there is a Fe-M
      interaction (kappa3 -D,Fe,D), in the form of a dative Fe->TM bond (TM=transition
      metal). This Minireview will explore the nature of this Fe-TM interaction
      thorough select examples as well as how to characterize a Fe->TM dative bond
      using physical, computational, and spectroscopic techniques.

PMID- 30238643
TI  - Incidence of antibiogram, antibiotic resistance genes and class 1 and 2 integrons
      in tribe Proteeae with IMP27 gene for the first time in Providencia sp. isolated
      from pet turtles.
AB  - Proteeae is a tribe which consists of three genera: Proteus, Providencia and
      Morganella. The objective of this study was to determine antimicrobial resistance
      profile, virulence genotype and class 1 and 2 integrons in Proteeae isolated from
      pet turtles and to determine the impact of antibiotic resistance on virulence and
      antimicrobial resistance genes. Integron-positive isolates were used to detect
      their gene cassette array. Sixty four Proteeae were isolated and all were
      resistant to macrolides (100%). Among 64 isolates 56, 52, 36 and 25 were
      resistant to nitrofurans, beta-lactams, tetracycline and aminoglycoside
      respectively. Sixteen (25%) isolates were positive for intI1 while 14 (21.87%)
      were positive for integrase 2 (intI2). Eleven (17.18%) isolates were positive for
      class 1 variable region while 7 (10.93%) were positive for class 2 variable
      region. IMP27, a novel metallo beta-lactamase gene was found in Providencia
      isolates. Proteus sp. were positive for every tested virulence genes and UreC
      gene was detected in 48.44% followed by zapA (17.19%), mrpA (17.19%) and hlyA
      (14.06%) genes. In this study, integron associated-antibiotic resistance genes
      have been identified in Proteeae isolates in a considerable range representing
      clear threats to public health. SIGNIFICANCE AND IMPACT OF THE STUDY: In this
      study, multidrug-resistant Proteeae isolates had several antibiotic resistance
      genes. Integrons are important contributors to the development and dissemination
      of antibiotic resistance. We could detect both class 1 and 2 integrons and
      several gene cassette arrays in class 1 integron. The gene cassette arrays of the
      Class 2 integrons contained IMP27-dfrA1-aadA1-catB2-ybeA-ybgA in two isolates. To
      the best of our knowledge this is the first study to report detection of IMP27 in
      Providencia rettgeri isolates. All results indicate that healthy pet turtles act
      as potential reservoirs for Proteeae species with zoonotic potential.

PMID- 30238644
TI  - Environmental risk factors for asthma in 13-14 year old African children.
AB  - Background Asthma prevalence in African children is high. Factors driving the
      prevalence or disease severity are poorly understood. This study aims to
      investigate environmental factors associated with asthma and severity in African
      children. Methods Population based cross-sectional study of children aged 13-14
      years from 10 African centers who participated in ISAAC III. Self-reported
      environmental exposures included engaging in physical exercise, television
      watching, various biomass and ETS exposure, consumption of paracetamol, large
      family sizes and having pets in the home. Univariable and multivariable analyses
      were done adjusting for center variations. Prevalences, odds ratio and 95%
      confidence intervals (CI) were calculated. Results There were 258 267 children
      recruited among the 13-14-year-old participants. Of these, 28,391 respondents
      from 232 schools completed both the written questionnaire (WQ) and environmental
      questionnaire (EQ). The prevalence of asthma and severe asthma were 12.8% (CI
      12.4-13.2), and 8.7% (CI 8.4-8.0) respectively. Factors strongly associated with
      asthma were maternal smoking (OR = 1.41; 95%CI: 1.23-1.64), open fire heating (OR
      = 1.28; 95%CI: 1.08-1.51) electric heating (OR = 1.13; 95%CI: 1.01-1.28),
      physical exercise (OR = 1.29; 95%CI: 1.11-1.50), monthly paracetamol use (OR
      1.23; 95%CI 1.13-1.33), having an elder sibling (OR = 0.87; 95%CI 0.77-0.98).
      Factors associated with severe asthma were maternal smoking (OR = 1.61; 95%CI:
      1.38-1.89), cat pet (OR = 1.14; 95%CI: 1.04-1.25), frequent physical exercise (OR
      = 1.42; 95%CI: 1.23-1.64) and monthly paracetamol use (OR = 1.20; 95%CI 1.07,
      1.34). Conclusion Several environmental exposures were associated with asthma and
      severe disease.

PMID- 30238645
TI  - Quantitative Comparison of Proteomes Using SILAC.
AB  - Stable isotope labeling by amino acids in cell culture (SILAC) has become very
      popular as a quantitative proteomic method since it was firstly introduced by
      Matthias Mann's group in 2002. It is a metabolic labeling strategy in which
      isotope-labeled amino acids are metabolically incorporated in vivo into proteins
      during translation. After natural (light) or heavy amino acid incorporation,
      differentially labeled samples are mixed immediately after cell lysis and before
      any further processing, which minimizes quantitative errors caused by handling
      different samples in parallel. In this unit, we describe protocols for basic
      duplex SILAC, triplex SILAC for use in nondividing cells such as neurons, and for
      measuring amounts of newly synthesized proteins. (c) 2018 by John Wiley & Sons,
      Inc.

PMID- 30238646
TI  - Towards developing a valid scoring tool for bronchitis during flexible
      bronchoscopy.
AB  - BACKGROUND: A valid bronchoscopic scoring tool for bronchitis would be useful for
      clinical and research purposes as currently there are none in children. From 100
      digitally recorded flexible bronchoscopies (FB), we related the various
      macroscopic features to airway neutrophil % to develop a FB-derived bronchitis
      score (BScoreexp ). We aimed to develop a FB-derived bronchitis tool. METHODS: FB
      recordings for six visualised features: secretions (amount and color) and mucosal
      appearance (erythema, pallor, ridging, oedema) based on pre-determined criteria
      on a pictorial chart were assessed by two physicians independently, blinded to
      the clinical history. These features were used to obtain various models of
      BScoreexp that were plotted against bronchoalveolar lavage (BAL) neutrophil %
      using a receiver operating characteristic (ROC) curve. Inter- and intra-rater
      agreement (weighted-kappa, K) were assessed from 30 FBs. RESULTS: Using BAL
      neutrophilia of 20% to define inflammation, the highest area under ROC (aROC) of
      0.71, 95%CI 0.61-0.82 was obtained by the giving three times weightage to
      secretion amount and color and adding it to erythema and oedema. Inter-rater K
      values for secretion amount (K = 0.87, 95%CI 0.73-1.0) and color (K = 0.86, 95%CI
      0.69-1.0) were excellent. Respective intra-rater K were 0.95 (0.87-1.0) and 0.68
      (0.47-0.89). Other inter-rater K ranged from 0.4 (erythema) to 0.64 (pallor).
      CONCLUSION: A repeatable FB-defined bronchitis scoring tool can be derived.
      However, a prospective study needs to be performed with larger numbers to further
      evaluate and validate these results.

PMID- 30238647
TI  - Evaluating bone remodeling by measuring Hounsfield units in a rabbit model of
      rhinosinusitis: is it superior to measuring bone thickness?
AB  - BACKGROUND: The traditional method of evaluating bone remodeling in chronic
      rhinosinusitis is to measure bone thickness. The objective of this study was to
      determine the feasibility of measuring the computed tomography (CT) value in
      Hounsfield units (HU) as an method and explore whether it is superior to
      measuring bone thickness. METHODS: The study was a prospective animal trial.
      Twenty normal rabbits were included in the control group, and 60 rabbit models
      were inoculated with Staphylococcus aureus to induce rhinosinusitis. The rabbit
      models were divided into 3 groups according to the time of infection. All animals
      were euthanized after the CT exam. The samples were scored based on mucus and
      bone changes. The rabbits were divided into negative and positive groups
      according to whether bone remodeling was observed. We obtained diagnostic
      threshold values by measuring the bone thickness and HU of each rabbit's
      maxillary sinus and compared the values obtained using the 2 methods by
      calculating the area under the receiver operating characteristic curve (AUC).
      RESULTS: The AUC for the measured bone thickness was 0.838, the diagnostic
      threshold was 1.165 mm. The AUC for the measured HU value was 0.937, the
      diagnostic threshold was 904.5. The correlation coefficients were r1 = 0.645 for
      the measured bone thickness and r2 = 0.797 for the HU measurement (r2 > r1 ; p <
      0.01). CONCLUSION: Evaluating bone remodeling is feasible by measuring either the
      bone wall thickness or the CT value. However, using CT to evaluate the sinus
      bones in rabbits with rhinosinusitis appears to be a more valuable option.

PMID- 30238648
TI  - Baseline visual acuity as a prognostic factor for visual outcomes in patients
      treated with aflibercept for wet age-related macular degeneration: data from the
      INSIGHT study using the Swedish Macula Register.
AB  - PURPOSE: To assess mean change in visual acuity (VA) overall and stratified by
      baseline VA after 1 and 2 years' treatment with aflibercept in a real-life
      setting. METHODS: This was an observational cohort study using nationwide data
      from the Swedish Macula Register. Treatment-naive patient eyes with wet age
      related macular degeneration and prescribed aflibercept from January 2013 to
      December 2014 were followed for 1 year (2478 eyes) or 2 years (831 eyes) to
      assess VA. Eyes were grouped by baseline VA. RESULTS: Mean number of injections
      in patients treated according to label (72%) versus patients treated not
      according to label was 8.0 +/- 1.5 versus 4.4 +/- 0.8 (p < 0.0001) at 1 year, and
      12.5 +/- 3.2 versus 7.3 +/- 1.9 (p < 0.0001) at 2 years. Among all eyes, mean VA
      increased from 61.3 +/- 13.4 Early Treatment Diabetic Retinopathy Study letters
      at baseline to 64.5 +/- 15.6 at 1 year and 65.1 +/- 15.1 letters at 2 years. At 2
      years, eyes with good baseline vision (>=70 letters) lost a mean of 2.4 +/- 11.3
      to 72.3 letters, eyes with intermediate baseline VA (36-69 letters) gained 5.7 +/
      14.1 to 62.7 letters, and eyes with poor baseline VA (<=35 letters) gained 13.2
      +/- 18.3 to 41.0 letters. Also at 2 years, 75% of treated eyes were stable or had
      improved VA. Among eyes with intermediate baseline VA, near vision was
      significantly better among those treated according to label versus not according
      to label at 3 (p = 0.019), 6 (p = 0.0002) and 12 months (p <= 0.0001).
      CONCLUSION: While gain in vision was especially pronounced in eyes with poor
      baseline VA, good baseline VA was important for best prognosis.

PMID- 30238649
TI  - Physical Activity and Worsening of Radiographic Findings in Persons With or at
      Higher Risk of Knee Osteoarthritis.
AB  - OBJECTIVE: The benefits of physical activity among persons with or at higher risk
      for knee osteoarthritis are well established. However, activity levels in this
      population are low, in part due to concern that activity will damage the knee
      joint. We hypothesized that sedentary and moderate-vigorous physical activity are
      each associated with greater risk of radiographic worsening of knee OA. METHODS:
      In Osteoarthritis Initiative participants with or at higher risk for knee OA
      enrolled in an accelerometer substudy at 48m (study baseline), physical activity
      was measured by uniaxial accelerometer (ActiGraph GT1M). Radiographic progression
      was defined as any 48m-96m KL grade worsening. All analyses were knee-level; we
      used multivariable logistic regression with GEE, adjusting for key covariates.
      RESULTS: 1206 persons [mean age 64 yrs (SD 9), 631 (52%) women, BMI 28 (5),
      average daily sedentary activity 602 minutes (86), light activity 284 minutes
      (75), moderate-vigorous activity 20 minutes (20)] contributed 1978 knees; 267
      (14%) had KL worsening. In the multivariable model, age, sex, BMI, and pain, but
      neither sedentary activity (adjusted OR 0.99, 95% CI 0.97-1.01) nor moderate
      vigorous activity (adjusted OR 1.00, 95% CI 0.91-1.09) were associated with KL
      worsening. CONCLUSION: In persons with or at higher risk for knee OA, age, sex,
      BMI, and pain - but not objectively measured average daily minutes of sedentary
      or moderate-vigorous activity - were associated with subsequent worsening of KL
      grade. Whether findings differ in persons with more severe knee OA and/or engaged
      more frequently in moderate-vigorous activity should be examined in future
      studies. This article is protected by copyright. All rights reserved.

PMID- 30238651
TI  - Proceedings of the 22nd Annual Conference of the European Society for Domestic
      Animal Reproduction (ESDAR), Cordoba, Spain, 27 - 29 September 2018.

PMID- 30238650
TI  - Self-management intervention using teach-back for people with heart failure in
      Vietnam: A cluster randomized controlled trial protocol.
AB  - Globally, the increasing prevalence of heart failure is a burden on health-care
      systems, especially in under-resourced countries, such as Vietnam. We describe a
      prospective single-site, cluster randomized controlled trial of an intervention
      designed to teach adult patients about heart failure and how to undertake self
      care activities. The intervention, delivered by a nurse, comprises of an
      individual teaching session using teach-back, a heart failure booklet, weighing
      scales, a diary to document daily weight, and a follow-up phone call 2 weeks
      after hospital discharge. Teach-back is a process of asking patients to repeat
      information and for the nurse to fill any gaps or misunderstanding until adequate
      understanding is demonstrated. The control group will receive usual education
      plus the heart failure (HF) booklet. A total of 140 participants will be
      allocated into two study groups. The level of randomization is at the ward level.
      The primary outcome (HF knowledge) and secondary outcomes (self-care behaviors
      and all-cause hospitalizations) will be measured at 1 and 3 months. This study
      will make an important contribution regarding a protocol of teach-back and
      chronic disease self-management.

PMID- 30238652
TI  - Gene expression analysis and in vitro production procedures for bovine
      preimplantation embryos: Past highlights, present concepts and future prospects.
AB  - Over the past decades in vitro production (IVP) of bovine embryos has been
      significantly improved and in particular bovine IVP is now widely applied under
      field conditions. This in vitro technique provides new opportunities for cattle
      producers, particularly in the dairy industry, to overcome infertility and to
      increase dissemination of animals with high genetic merit. Improvements in
      OPU/IVP resulted in large-scale international commercialization. More than half a
      million IVP embryos are generated on the yearly basis demonstrating the enormous
      potential of this technology. These advances and the fact that bovine and human
      early development is remarkably similar have also prompted the use of bovine
      embryos as a model system to study early mammalian embryogenesis including
      humans. Despite all the improvements, embryos generated in vitro still differ
      from their in vivo derived counterparts. Embryos must adjust to multiple
      microenvironments at preimplantation stages. Consequently, maintaining or
      mimicking the in vivo situation in vitro will aid to improve the quality and
      developmental competence of the resulting embryo. The successful clinical
      application of the techniques in reproductive biotechnology requires both species
      specific clinical skills and extensive laboratory experience. The recent advances
      in transcriptome profiling have also provided deeper insight into RNA expression
      and regulation at an unprecedented resolution. The development of these high
      throughput DNA sequencing methods has resulted in new approaches for both mapping
      and quantifying transcriptomes. The aim of this review is therefore to summarize
      the available data related to gene expression analyses as well as in vitro embryo
      production procedures and to provide ideas about future concepts.

PMID- 30238653
TI  - Recent advances in pig reproduction: Focus on impact of genetic selection for
      female fertility.
AB  - In the past 30 years, sows have been successfully selected for a shorter weaning
      to-oestrus interval and increased litter size. This review discusses the
      consequences of this selection for the reproductive physiology of sows, including
      the consequences for litter characteristics at birth. It also discusses breeding
      and management opportunities to deal with this changed genetics.

PMID- 30238654
TI  - Gene expression and immunolocalization of low-affinity neurotrophin receptor
      (p75) in rabbit male reproductive tract during sexual maturation.
AB  - This study reports the gene expression and immunolocalization of the low-affinity
      neurotrophin receptor, p75, in accessory glands (prostate and bulbourethral
      glands) and epididymis (caput and cauda) of male rabbits during sexual
      maturation. We showed that p75 was expressed in all tissues studied with similar
      mRNA levels during this period. However, it was differentially immunolocalized in
      bulbourethral glands and stereocilia of epididymis. These findings may be related
      with some remodeling processes in the accessory glands during sexual maturation,
      which could be associated with sperm maturation. The interaction of p75 with
      neurotrophins in rabbit male reproductive tract suggests the possible implication
      of this system in sexual maturation in rabbits.

PMID- 30238655
TI  - Embryonic maternal interaction in cattle and its relationship with fertility.
AB  - Embryo mortality is a major contributor to poor reproductive efficiency and
      profitability in cattle production systems. While conception is achieved (i.e.,
      the oocyte is fertilized) in the vast majority of cases if insemination is
      carried out correctly, a significant proportion of the resulting embryos fail to
      develop to term. Appropriate communication between the developing conceptus and
      the maternal endometrium is essential for the establishment and maintenance of
      pregnancy in all mammals. Up to the blastocyst stage, around Days 7-9, contact
      worth the female reproductive system is not required. However, the process of
      conceptus elongation after hatching and prior to implantation is entirely
      maternally driven and is essential to ensure that sufficient quantities of
      interferon-tau (IFNT) are secreted by the developing conceptus to abrogate the
      mechanisms that bring about luteolysis. While the importance of conceptus-derived
      IFNT in maternal recognition of pregnancy and prevention of luteolysis in cattle
      is unequivocal, many questions, such as the threshold level of IFNT required for
      pregnancy maintenance, remain unanswered. Furthermore, the precise role of IFNT
      independent mechanisms in pregnancy establishment remains to be elucidated.
      Irrespective of this, failure of the conceptus to elongate undoubtedly results in
      embryonic loss and is thus believed to contribute greatly to reproductive failure
      in cattle. This review will address some of these answered questions and try to
      shed some light on those gaps in knowledge that could potentially contribute to
      improved embryo survival and reproductive efficiency.

PMID- 30238656
TI  - Effects of testicular hemodynamic and echogenicity changes on ram semen
      characteristics.
AB  - This study investigated correlations among ram semen quality parameters,
      testicular vascularity and echotexture. Measurements were performed biweekly for
      a year, before (BE) and after ejaculation (AE), on seven Chios breed rams [three
      rams (group A) and four rams (group B) of 2-6 and 9-13 years old, respectively],
      considering breeding (1) and non-breeding period (2). Hemodynamics [Pulsatility
      Index (PI), Resistive Index (RI)] were evaluated in each testis. Images of
      testicular parenchyma were analysed to evaluate echogenicity [Mean Value (MV),
      Contrast (Con), Gray Value Distribution (GVD), Run Length Distribution (RunLD),
      Long Run Emphasis (LRunEm)]. Semen volume (V), concentration (C), kinetics
      (CASA), morphology (Sperm Blue), viability (Eosin-Nigrosin) and DNA fragmentation
      (Acridine Orange) were assessed. In group A/2, semen V was correlated to left
      testis PI and right testis RI, BE (r = 0.4, p = 0.013/r = 0.6, p < 0.001,
      respectively), and to right testis PI and RI, AE (r = 0.5, p < 0.001). In A/1/AE,
      semen C was correlated to left testis PI (r = -0.5, p = 0.003). In group A/1/BE,
      RI of both testes was correlated to total and tail abnormalities (left: r = -0.5,
      p = 0.008/ p = 0.004, respectively - right: r = -0.4/r = -0.5, p = 0.01/ p =
      0.008, respectively). In group B/1/BE, sperm tail and total abnormalities were
      correlated to left testis Con (r = 0.5, p = 0.02/ p < 0.001, respectively),
      whereas in A/2/BE, they were correlated to left testis LRunEm (r = -0.8/r = -0.7,
      p < 0.001, respectively). In group A/1/BE, DNA damage was correlated to right
      testis LRunEm (r = -0.6, p < 0.001) and tail abnormalities to left testis PI (r =
      -0.5, p = 0.03). In group B/1/AE, right testis LRunEm, GVD, RunLD, were
      correlated to sperm DNA integrity (r = -0.9, p < 0.001). Immotile spermatozoa and
      viability were correlated to left testis Con in group B/2/AE (r = -0.6/r = 0.6, p
      < 0.001) and to right testis MV in group A/1/AE (r = -0.6/r = 0.6, p < 0.001). In
      conclusion, alterations in both ram testes blood flow and echotexture seem to be
      moderately correlated with sperm assessed parameters, depending on season and ram
      age.

PMID- 30238657
TI  - Editorial.

PMID- 30238658
TI  - Vitrification in straws conserves motility features better than spheres in donkey
      sperm.
AB  - Sperm vitrification as alternative to conventional freezing is increasing in
      popularity in many species. It has been achieved by direct exposure of diluted
      semen to liquid nitrogen in spheres or straws. Both techniques have been
      successfully developed, but they had not been compared yet in donkeys. The aim of
      this study was to compare these two methods of vitrification for donkey semen.
      Ejaculates from six Andalusian donkeys were collected and extended in Gent
      without glycerol supplemented with sucrose 0.1 M (Molar). Samples were slowly
      cooled at 5 degrees C. For vitrification, 30 MUl suspensions (spheres) were
      dropped directly into liquid nitrogen (LN2 ) or filled in covered 0.25 ml straws
      and then plunged into the LN2 (straws). For warming, straws and spheres were
      directly immersed in 3 ml of INRA-96 at 43 degrees C. Total (TM, %) and
      progressive motility (PM, %) were objectively evaluated by computer-assisted
      sperm analysis and plasma membrane integrity (PMI, %) by epifluorescence
      microscopy. Results showed the straw method resulted in significantly higher
      values than spheres for: TM (54.7% +/- 10.1 vs. 28.6% +/- 6.5) and PM (44.2% +/-
      9.4 vs. 17.7% +/- 6.4), but no significant differences were found between straws
      or spheres for PMI (31.5 +/- 10.7 vs. 41.6 +/- 14.3) respectively. In conclusion,
      donkey sperm could be vitrified in straws obtaining better sperm motility
      parameters after warming in comparison to the sphere method.

PMID- 30238659
TI  - Extracellular vesicles derived from endometrial human mesenchymal stem cells
      improve IVF outcome in an aged murine model.
AB  - Advanced age reduces the success of in vitro fertilization (IVF) being this
      effect partly mediated by an overproduction of reactive oxygen species (ROS) that
      trigger apoptosis. It has been demonstrated that extracellular vesicles derived
      from endometrial mesenchymal stem cells (EV-endMSCs) exert an antioxidant effect
      and can be used as IVF coadjutants. In this work, endMSCs were isolated from
      human menstrual blood (n = 4) and characterized according to multipotentiality
      and surface marker expression prior EV-endMSCs isolation. Oocytes were obtained
      from 21 B6D2 mice (24 weeks) and coincubated with sperm from young males (8-12
      weeks). Presumptive zygotes were incubated in the presence of 0, 10, 20, 40 or 80
      MUg/ml of EV-endMSCs in KSOM medium. Blastocyst yield was evaluated, and 25
      blastocysts per group were used for qPCR. Blastocyst rate was 29.4% in control;
      45.2% for 10 MUg/ml, 62.9% for 20 MUg/ml, 55.5% for 40 MUg/ml and 53.8% in the 80
      MUg/ml (n = 124-130 oocytes) being all the increases significantly different when
      compared against control (p < 0.05). The 20-80 MUg/ml treatments decreased the
      expression of glutathione peroxidase (Gpx1), and the 10-40 MUg/ml treatments
      reduced the expression of superoxide dismutase (Sod1; p < 0.05) compared to
      control; Bax mRNA expression did not vary. Our results suggest that the increased
      developmental competence of the embryos could be partly mediated by the EV
      endMSCs' ROS scavenger activity.

PMID- 30238660
TI  - Ejaculation effect on blood testosterone and prostatic pulsed-wave Doppler
      ultrasound in dogs.
AB  - Local vessels ultrasonography evaluates prostatic physio-pathologic states.
      Testosterone promotes tissue and vascular growth. Knowing variables on prostatic
      vasculature is crucial to correctly apply Pulsed-Wave exam. The study aims to
      assess how ejaculation and blood testosterone affect Pulsed-Wave indexes. Serial
      blood testosterone dosages and Pulsed-Wave exams were performed in 20 dogs,
      immediately before (T0) and after (T1) ejaculation and 6 hr later (T2). Arteria
      prostatica cranialis, Arteriola capsularis, Arteriola trabecularis and Arteriola
      parenchimalis were evaluated and mean Pulsatility and Resistivity Index, Systolic
      Peak, End-Diastolic and Mean Velocity calculated. Data were grouped by time and
      vessel (ANOVA, p <= 0.05). At T1, Resistivity Index significantly lowered in A.
      prostatica cranialis, A. trabecularis and A. parenchimalis but grew in A.
      capsularis; Pulsatility Index had the same pattern, but not significant in A.
      parenchimalis; Systolic Peak Velocity, End-Diastolic Velocity, Mean Velocity
      significantly rose in A. capsularis and A. trabecularis. No indexes differed at
      T0 and T2. Testosterone did not differ at T0 (10.93 +/- 7.05 ng/ml), T1 (12.71 +/
      7.29) and T2 (10.54 +/- 6.63). Results stated the risen prostatic vascular flow
      postejaculation, affecting Pulsed-Wave. Due to semi-rigid capsule, impairing
      vasodilation of other vessels, only A. capsularis indexes increased. Intimal
      cushions of A. prostatica cranialis kept velocities fixed; A. capsularis and A.
      trabecularis lack of intimal cushions, thus velocities grew. In A. parenchimalis,
      precapillary sphincters opening allows increased flow redistribution in
      vasodilated parenchymal bed, keeping velocities fixed. As testosterone, not
      affected by ejaculation, did not peak, vascular changes are not due to
      testosterone itself. These physiological effects of ejaculation suggest proper
      sexual rest before Pulsed-Wave exam planned to explore suspected prostatic
      neovascularization.

PMID- 30238661
TI  - Assisted reproductive techniques in mares.
AB  - A wide variety of assisted reproductive techniques (ARTs) are available to aid in
      managing aspects of equine reproduction. Embryo recovery and transfer can be used
      to obtain more than one foal per mare per year, and to obtain foals from mares
      that cannot carry a foal to term. Oocyte recovery and either transfer to the
      oviduct of an inseminated recipient mare (oocyte transfer), or intracytoplasmic
      sperm injection (ICSI) and embryo culture can be used to obtain foals from mares
      with some types of subfertility, such as problems of the tubular tract. ICSI can
      be used to obtain foals when sperm number or quality is low. Because of its ease
      of use for the mare owner and efficiency, oocyte recovery and ICSI is being used
      in some cases for management of normally fertile mares and stallions. Oocytes can
      be recovered from live mares by the referring veterinarian, and shipped overnight
      to a laboratory for ICSI, without any decrease in oocyte or embryo viability. In
      case of unexpected death of a mare, ovaries or oocytes can be transported to the
      ICSI laboratory for production of embryos. Embryos produced both in vitro and in
      vivo can be biopsied to determine their genetic makeup before they are
      transferred. Equine embryos can be vitrified successfully; collapse of the
      blastocoele cavity allows efficient vitrification of expanded blastocysts. In
      contrast, cryopreservation of unfertilized equine oocytes still has low success.
      Genetics of valuable animals can be preserved via nuclear transfer (cloning) and
      several commercial companies offer this service clinically.

PMID- 30238662
TI  - Flow cytometry analysis of spermatozoa: Is it time for flow spermetry?
AB  - Flow cytometry is increasingly used in research and also in clinical andrology.
      Recent developments in instrumentation, availability of probes and bioinformatics
      expand the possibilities of flow cytometry well beyond the classical two
      parametric analyses in use. In this paper, an overview of recent developments in
      flow cytometry will be presented under the perspective of the authors; aspects
      such a multicolor assays and computational cytometry will be discussed as well.

PMID- 30238663
TI  - Comparison of different sucrose-based extenders for stallion sperm vitrification
      in straws.
AB  - Vitrification of sperm is based on high-speed freezing by direct exposure to
      liquid nitrogen using non-permeable cryoprotectants, mainly disaccharides; yet,
      the concentration of cryoprotectants has a species-specific effect on the sperm
      cell. The aim of this study was to assess different sucrose concentrations for
      stallion sperm vitrification. Semen samples (n = 9) were collected from three
      stallions, centrifuged and resuspended to a concentration of 50 * 106  sperm/ml
      in a base extender (INRA96 + 1% of bovine serum albumin) with three different
      sucrose concentrations (Molar): 20 mM (S1), 100 mM (S2), or 200 mM (S3). Then,
      sperm were filled in covered 0.25 ml straws and directly plunged into liquid
      nitrogen. For warming, 0.25 ml straw was pulled out the covering straw and
      immersed in 3 ml of INRA96 at 43 degrees C, with gentle pipetting to accelerate
      the melting. Total (TM, %) and progressive sperm motility (PM, %) were analysed
      using computer-assisted sperm analysis. Plasma (PMI, %) and acrosome membrane
      integrity (AIS, %) were assessed under epifluorescence microscopy. Post-warmed
      sperm parameters were compared between treatments by ANOVA. S2 showed
      significantly higher values in comparison with S1 and S3 for TM (S2 = 54.7 +/-
      5.5a ; S1 = 29.1 +/- 3.3b ; S3 = 28.6 +/- 3.0b ; p < 0.001) and PM (S2 = 31.3 +/-
      3.8a ; S1 = 18.5 +/- 2.6b ; S3 = 17.7 +/- 2.9b ; p < 0.01), respectively. No
      significant differences were found among treatments for PMI (S2 = 70.3 +/- 5.2;
      S1 = 67.4 +/- 4.3; S3 = 70.0 +/- 3.7) neither for AIS (S2 = 57.1 +/- 3.9; S1 =
      53.9 +/- 4.2; S3 = 57.0 +/- 7.9). In conclusion, a concentration of 100 mM
      sucrose is recommended for stallion sperm vitrification in straws.

PMID- 30238665
TI  - Reliability and validity of the Hebrew version of the Nijmegen Continuity
      Questionnaire for measuring patients' perceived continuity of care in oral
      anticancer therapy.
AB  - To assess the validity and reliability of the Nijmegen Continuity Questionnaire
      in Hebrew (NCQ-H) for measuring patients' perceived continuity of care in the
      multiprovider setting of oral anticancer therapy (OACT). Following forward
      backward translation of the original instrument into Hebrew, the NCQ-H was
      administered to adult cancer patients in five oncology centres in Israel, 2-3
      months after initiation of OACT (either targeted, hormonal or chemotherapy).
      Confirmatory factor analysis and Cronbach's alpha were used to assess the
      validity and reliability of the NCQ-H respectively. A total of 135 patients
      completed the questionnaire. The postanalysis models for measuring "personal
      continuity with care provider" (eight items for each provider: the oncology
      specialist and the primary care physician), and "team/cross-boundary continuity"
      (four items for each setting: within the oncology team, and between the oncology
      specialist and the primary care physician) showed good fit for the observed data
      (root-mean-square error of approximation (RMSEA) = 0.02; RMSEA = 0.015; for each
      model respectively). Cronbach's alpha was 0.79-0.95 for all subscales.
      Conclusions. This study provides preliminary evidence for the reliability and
      validity of the NCQ-H in assessing cancer patients' experience with continuity of
      care and for its usability in the context of OACT.

PMID- 30238664
TI  - Elastase inhibition affects collagen transcription and prostaglandin secretion in
      mare endometrium during the estrous cycle.
AB  - We have shown that bacteria induce neutrophil extracellular traps (NETs) in mare
      endometrium. Besides killing pathogens, NETs may contribute for endometrosis
      (chronic endometrium fibrosis). Since elastase (ELA) is a NETs component that
      regulates fibrosis and prostaglandin (PG) output, the aim was to evaluate if
      inhibition of ELA would affect collagen 1 (COL1) transcription and PGs secretion
      by endometrium explants, in different estrous cycle phases. Follicular-FP (n = 8)
      and mid luteal-MLP (n = 7) phases explants were cultured for 24-48 hr with medium
      alone (Control), ELA (0.5 MUg/ml,1 MUg/ml), sivelestat - ELA inhibitor (INH,10
      MUg/ml), or ELA (0.5 MUg/ml,1 MUg/ml) + INH (10 MUg/ml). COL1 gene transcription
      was done by qRT-PCR and PGE2 and PGF2 alpha determination in culture medium by
      EIA. In FP, at 24 hr, ELA0.5 increased COL1 transcription (p < 0.001) but its
      inhibition (ELA0.5 + INH10) decreased COL1 transcription (p < 0.01) and PGF2
      alpha production (p < 0.05). Also, ELA0.5 + INH10 or ELA1 + INH10 raised PGE2
      production (p < 0.01). At 48 hr, ELA1 increased COL1 transcription (p < 0.01) and
      PGF2 alpha production (p < 0.001), but its inhibition (ELA1 + INH10) decreased
      these actions (p < 0.01; p < 0.05, respectively). Besides, ELA1 + INH10
      incubation increased PGE2 (p < 0.05). PGF2 alpha also augmented with ELA0.5 (p <
      0.001), but lowered with ELA0.5 + INH10 (p < 0.01). In MLP, ELA0.5 up-regulated
      COL1 transcription (24 hr, p < 0.01; 48 hr, p < 0.001), but ELA0.5 + INH10
      decreased it (24 hr, p < 0.05; 48 hr, p < 0.001). At 48 hr, incubation with ELA1
      also increased COL1 transcription and PGF2 alpha production (p < 0.05), but PGF2
      alpha production decreased with ELA1 + INH10 incubation (p < 0.05). PGE2
      production was higher in ELA1 + INH10 incubation (p < 0.05). Therefore, ELA
      inhibition may reduce the establishment of mare endometrial fibrosis by
      stimulating the production of anti-fibrotic PGE2 and inhibiting pro-fibrotic PGF2
      alpha.

PMID- 30238666
TI  - Measurement invariance of the Spanish Launay-Slade Hallucinations Scale-Extended
      version between putatively healthy controls and people diagnosed with a mental
      disorder.
AB  - OBJECTIVES: The current study aimed at evaluating the reliability, convergent and
      divergent validity, and factor structure of the Spanish Launay-Slade
      Hallucinations Scale-Extended version (LSHS-E) in people with mental disorders
      and healthy controls. METHODS: Four hundred and twenty-two individuals completed
      the Spanish LSHS-E and the Spanish Community Assessment of Psychic Experiences.
      The convergent and divergent validity of the LSHS-E was assessed with the three
      dimensions of the Community Assessment of Psychic Experiences (positive,
      negative, and depressive dimensions) in healthy controls and people with a mental
      disorder. Factor structure of the LSHS-E was assessed using confirmatory factor
      analysis and measurement invariance. RESULTS: The LSHS-E had a good reliability
      in healthy controls and people with a mental disorder (Cronbach's = 0.83 and
      0.91, respectively). The LSHS-E was more strongly associated with positive
      psychotic-like experiences than with depressive and negative symptoms. Four
      factors were found: (a) "intrusive thoughts"; (b) "vivid daydreams"; (c)
      "multisensory hallucination-like experiences"; and (d) "auditory-visual
      hallucination-like experiences" that were invariant between the group of healthy
      controls and people with a mental disorder. CONCLUSION: The Spanish version of
      the LSHS-E possesses adequate psychometric properties, and the confirmatory
      factor analysis findings provide further support for the multidimensionality of
      proneness to hallucination in clinical and nonclinical samples.

PMID- 30238667
TI  - Ideal embryo transfer position and endometrial thickness in IVF embryo transfer
      treatment.
AB  - OBJECTIVE: To establish an ideal transfer strategy by investigating the
      relationships among embryo transfer (ET) depth, endometrial thickness, and
      subsequent in vitro fertilization treatment clinical pregnancy outcomes. METHODS:
      In the present retrospective analysis, data from in vitro fertilization-ET
      treatment cycles conducted at a fertility center in Shanghai, China, between
      October 2014 and March 2015 were analyzed. Women were divided into groups 1-4
      according to transfer depth (<10; 10-15, 15-20, and >20 mm, respectively), as
      measured by air bubbles. Additionally, 391 women were divided into groups A-C
      according to endometrial thickness (<7, 1-12, and >12 mm, respectively). Clinical
      pregnancy outcomes were assessed by group. RESULTS: Data from 501 cycles were
      included. Clinical pregnancy and live delivery rates were significantly higher in
      group 2 (P=0.009 and P=0.002, respectively) and group 3 (P=0.008 and P=0.001,
      respectively) than in group 4. Among the 394 patients with endometrial thickness
      data available, clinical pregnancy and live delivery rates were higher in group B
      (P=0.028 and P=0.015, respectively) and group (P=0.013 and P=0.013, respectively)
      than in group A. CONCLUSION: Correct transfer depth and endometrial thickness can
      increase the rates of clinical pregnancy, implantation, and live delivery.
      Placing the embryos at 10-20 mm from the fundus and at an endometrial thickness
      of more than 7 mm is recommended for optimal clinical pregnancy outcomes.

PMID- 30238669
TI  - The prevalence of the defining features of primary ciliary dyskinesia within a
      cri du chat syndrome cohort.
AB  - BACKGROUND: Primary ciliary dyskinesia (PCD) and cri du chat syndrome (CdCS) are
      distinct disorders that can co-occur due to a common genetic locus on chromosome
      5p. Chronic respiratory symptoms associated with PCD can occur in CdCS and are
      typically attributed to hypotonia, dysphagia, and aspiration. The prevalence of
      PCD among individuals with CdCS is not known. METHODS: An online survey assessing
      common features of PCD was distributed to members of the 5P Minus Society, a cri
      du chat patient advocacy group. Respondents who met criteria for elevated risk of
      PCD (at least 3 symptoms or other features highly suggestive of PCD) were offered
      PCD genetic testing. RESULTS: For the 123 respondents (median age 10.1 years with
      IQR 5.5-17.3 years; from 33 U.S. states and 10 other countries) chronic
      respiratory symptoms associated with PCD were prevalent, including unexplained
      neonatal respiratory distress, year-round nasal congestion beginning in infancy,
      and year-round, wet cough beginning in infancy in 35%, 32%, and 20% of
      respondents, respectively. Fifteen respondents (12%) met criteria for elevated
      risk for PCD and completed genetic analysis; however, none were diagnostic for
      PCD. A PCD clinical center evaluated an additional subject with CdCS who met
      criteria for likely PCD and had negative genetics, but had diagnostic electron
      microscopy of the respiratory cilia (missing outer dynein arms). CONCLUSION:
      Clinicians should be aware of the genetic connection between CdCS and PCD. Non
      informative genetic testing does not rule out PCD. CdCS patients with chronic
      respiratory symptoms may benefit from referral to specialized PCD diagnostic
      centers.

PMID- 30238670
TI  - Relationship between authentic leadership and nurses? intent to leave: The
      mediating role of work environment and burnout.
AB  - AIM: The aim of this study was to explore the mediating effects of work
      environment and burnout on the relationship between authentic leadership and the
      intention of nurses to leave their job. BACKGROUND: Authentic leadership can
      contribute to a good work environment. Burnout is a critical factor that affects
      nurses? intent to leave. The mediating roles of work environment and burnout on
      the relationship between authentic leadership and intent to leave is unclear.
      METHODS: A cross-sectional design was used, and 946 nurses from three different
      levels of hospital (medical center, regional, and district), defined in terms of
      the number of beds and type of medical care provided, responded to four self
      report questionnaires. RESULTS: Work environment and burnout mediated the effect
      of authentic leadership on intent to leave among nurses. The mediating effects of
      burnout on authentic leadership was present both for junior (beta = 0.073) and
      senior (beta = 0.081) nurses. CONCLUSION: Authentic leadership can affect nurses?
      intent to leave but the work environment and burnout are important mediators of
      this influence. IMPLICATIONS FOR NURSING MANAGEMENT: Administrators should adopt
      authentic leadership practices and make efforts to improve the work environment
      and decrease burnout in order to decrease nurses? intent to leave.

PMID- 30238668
TI  - Secretome of Undifferentiated Neural Progenitor Cells Induces Histological and
      Motor Improvements in a Rat Model of Parkinson's Disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative movement disorder
      that results from the death of dopamine (DA) neurons. Over recent years,
      differentiated or undifferentiated neural stem cells (NSCs) transplantation has
      been widely used as a means of cell replacement therapy. However, compelling
      evidence has brought attention to the array of bioactive molecules produced by
      stem cells, defined as secretome. As described in the literature, other cell
      populations have a high-neurotrophic activity, but little is known about NSCs.
      Moreover, the exploration of the stem cell secretome is only in its initial
      stages, particularly as applied to neurodegenerative diseases. Thus, we have
      characterized the secretome of human neural progenitor cells (hNPCs) through
      proteomic analysis and investigated its effects in a 6-hydroxidopamine (6-OHDA)
      rat model of PD in comparison with undifferentiated hNPCs transplantation.
      Results revealed that the injection of hNPCs secretome potentiated the
      histological recovery of DA neurons when compared to the untreated group 6-OHDA
      and those transplanted with cells (hNPCs), thereby supporting the functional
      motor amelioration of 6-OHDA PD animals. Additionally, hNPCs secretome proteomic
      characterization has revealed that these cells have the capacity to secrete a
      wide range of important molecules with neuroregulatory actions, which are most
      likely support the effects observed. Overall, we have concluded that the use of
      hNPCs secretome partially modulate DA neurons cell survival and ameliorate PD
      animals' motor deficits, disclosing improved results when compared to cell
      transplantation approaches, indicating that the secretome itself could represent
      a route for new therapeutic options for PD regenerative medicine. Stem Cells
      Translational Medicine 2018;7:829-838.

PMID- 30238671
TI  - "It's like all of his attention is on you": A mixed methods examination of
      attachment, supportive nonparental youth-adult relationships, and self-esteem
      during adolescence.
AB  - The purpose of this mixed methods study was to examine the relationship between
      attachment, supportive nonparental youth-adult relationships, and self-esteem
      during adolescence. First, in a quantitative path analysis, we found that
      perceived social support from nonparental adults partially mediated the
      relationship between adolescent attachment and self-esteem. In our follow-up
      mixed methods analysis, we analyzed youth reflections of support experienced in
      relationships with significant non-parental adults (VIPs). As compared to youth
      with positive attachment models, youth with negative attachment models reported
      fewer instances of emotional support but more instances of validation support.
      The youth with negative attachment models described (1) the importance of trust
      and (2) receiving emotional support specific to their needs. In instances of
      validation support, these youth described how their VIPs (1) provided them with
      honest and realistic feedback, (2) challenged their negative thinking and (3)
      created opportunities for them to recognize and showcase their strengths. Our
      findings underscore the importance of considering youths' individual attributes
      in the context of their ongoing relationships in order to gain a more nuanced
      understanding of the role and dynamics of supportive nonparental youth-adult
      relationships in youths' lives.

PMID- 30238672
TI  - Structural Features on the Substrate-Binding Surface of Fungal Lytic
      Polysaccharide Monooxygenases Determine Their Oxidative Regioselectivity.
AB  - Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that
      oxidatively cleave many of nature's most recalcitrant polysaccharides by acting
      on the C1- and/or C4-carbon of the glycosidic bond. Here, the results of an
      extensive mutagenesis study on three LPMO representatives, Phanerochaete
      chrysosporium LPMO9D (C1-oxidizer), Neurospora crassa LPMO9C (C4), and Hypocrea
      jecorina LPMO9A (C1/C4), are reported. Using a previously published indicator
      diagram, the authors demonstrate that several structural determinants of LPMOs
      play an important role in their oxidative regioselectivity. N-glycan removal and
      alterations of the aromatic residues on the substrate-binding surface are shown
      to alter C1/C4-oxidation ratios. Removing the carbohydrate binding module (CBM)
      is found not to alter the regioselectivity of HjLPMO9A, although the effect of
      mutational changes is shown to increase in a CBM-free context. The accessibility
      to the solvent-exposed axial position of the copper-site reveales not to be a
      major regioselectivity indicator, at least not in PcLPMO9D. Interestingly, a
      HjLPMO9A variant lacking two surface exposed aromatic residues combines decreased
      binding capacity with a 22% increase in synergetic efficiency. Similarly to
      recent LPMO10 findings, our results suggest a complex matrix of surface
      interactions that enables LPMO9s not only to bind their substrate, but also to
      accurately direct their oxidative force.

PMID- 30238673
TI  - Low-dose bisphenol A induces RIPK1-mediated necroptosis in SH-SY5Y cells: Effects
      on TNF-alpha and acetylcholinesterase.
AB  - Bisphenol A (BPA) is an endocrine disruptor chemical, which is commonly used in
      everyday products. Adverse effects of its exposure are reported even at picomolar
      doses. Effects of picomolar and nanomolar concentrations of BPA on cytotoxicity,
      nitric oxide (NO) levels, acetylcholinesterase (AChE) gene expression and
      activity, and tumor necrosis factor-alpha (TNF-alpha) and caspase-8 levels were
      determined in SH-SY5Y cells. The current study reveals that low-dose BPA
      treatment induced cytotoxicity, NO, and caspase-8 levels in SH-SY5Y cells. We
      also evaluated the mechanism underlying BPA-induced cell death. Ours is the first
      report that receptor-interacting serine/threonine-protein kinase 1-mediated
      necroptosis is induced by nanomolar BPA treatment in SH-SY5Y cells. This effect
      is mediated by altered AChE and decreased TNF-alpha levels, which result in an
      apoptosis-necroptosis switch. Moreover, our study reveals that BPA is an
      activator of AChE.

PMID- 30238674
TI  - A general gas-assisted three-liquid-phase extraction method for separation and
      concentration of puerarin, 3'-methoxydaidzin, puerarinxyloside, daidzin and
      daidzein from puerariae extract.
AB  - In this work, a general and novel separation technique gas-assisted three-liquid
      phase extraction was established and applied in separating and concentrating
      isoflavonoids from the actual sample of puerariae extract by one step. For the
      gas-assisted three-liquid-phase extraction method, optimal conditions were
      selected: polyethylene glycol 2000 and ethyl acetate as the flotation solvent, pH
      5, (NH4 )2 SO4 concentration 350 g/L in aqueous phase, N2 flow rate 30 mL/min,
      flotation time 50 min, and flotation twice. Five isoflavonoids compounds
      puerarin, 3'-methoxydaidzin, puerarinxyloside, daidzin and daidzein were
      separated with recoveries of 82, 84, 80, 88 and 89%, respectively. The separated
      products were purified by preparative high-performance liquid chromatography, and
      the purity of the final products was >96%. The established general gas-assisted
      three-liquid-phase extraction was used to separate anthraquinones from Cassiae
      Semen under the optimal conditions, and the recoveries were >75%. The
      experimental results showed that the established gas-assisted three-liquid-phase
      extraction method is a general technique for separating active compounds from
      herb extract.

PMID- 30238675
TI  - Swedish men and smoking: Views on screening-detected abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysms (AAA), most common among elderly male smokers, often
      show no symptoms before rupture. To facilitate better care and counselling
      targeted to smoking cessation for these patients, more knowledge is required
      about their views. Therefore, the aim of the present study was to describe the
      views on AAA and smoking among male smokers with screening-detected AAA. A
      qualitative approach with individual interviews with 16 men with screening
      detected AAA was applied. Three had quit smoking by the time of the interviews.
      Thematic analysis was performed, and four themes emerged: (i) accepting the
      course of life; (ii) the elusive AAA: a disturbing experiencing or merely a minor
      inconvenience?; (iii) being in safe hands; and (iv) smoking as an unexpected
      topic of discussion. Most of the participants felt they were in "safe hands",
      although thoughts about death were also evoked. However, the information about
      smoking cessation was unexpected, and the relationship between AAA and smoking
      unclear. Presenting the connection between AAA and smoking in a clear manner and
      motivating smoking cessation in an individually-targeted way are important.

PMID- 30238676
TI  - Pressure injuries in critical patients: Incidence, patient-associated factors,
      and nursing workload.
AB  - AIM: To estimate the incidence of pressure injury and its predictors including
      nursing workload in critical patients. BACKGROUND: There is controversy about the
      influence of the nursing workload on the occurrence of pressure injury in
      intensive care units. METHODS: A retrospective cohort of 766 patients in nine
      intensive care units of two university hospitals was studied. The nursing
      workload was measured using the Nursing Activities Score. The predictors were
      identified by logistic regression. RESULTS: The pressure injury incidence was
      18.7%. The odds ratio of the development of pressure injury, increased 3.5 times
      in mechanical ventilation (p < 0.001), 7.8 times in palliative care (p = 0.004),
      2.3 times in the 60-84 years old group (p = 0.005); it also increased 10% for
      each day of hospitalization (p < 0.001), and 1.5% for each registered point of
      the Nursing Activities Score (p = 0.016). CONCLUSION: Existing risks for the
      development of pressure injury have been confirmed and nursing workload
      identified as a new predictor. Much still needs to be done in the area of
      prevention, especially in groups at risk. IMPLICATIONS FOR NURSING MANAGEMENT:
      Increasing nursing resources in the intensive care unit may assist in reducing
      the pressure injury rate.

PMID- 30238677
TI  - Palladium Phosphide as a Stable and Efficient Electrocatalyst for Overall Water
      Splitting.
AB  - A palladium phosphide electrocatalyst supported on carbon black (PdP2 @CB) shows
      efficient water splitting in both alkaline and neutral electrolytes.
      Significantly lower overpotentials are required for PdP2 @CB (27.5 mV in 0.5 m H2
      SO4 ; 35.4 mV in 1 m KOH; 84.6 mV in 1 m PBS) to achieve a HER electrocatalytic
      current density of 10 mA cm-2 compared to commercial Pt/CB (30.1 mV in 0.5 m H2
      SO4 ; 46.6 mV in 1 m KOH; 122.7 mV in 1 m PBS). Moreover, no loss in HER activity
      is detectable after 5000 potential sweeps. Only 270 mV and 277 mV overpotentials
      are required to reach a current density of 10 mA cm-2 for PdP2 @CB to catalyze
      OER in 1 m KOH and 1 m PBS electrolytes, which is better OER activity than the
      benchmark IrO2 electrocatalyst (301 mV and 313 mV to drive a current density of
      10 mA cm-2 ). 1.59 V and 1.72 V are needed for PdP2 @CB to achieve stable water
      splitting catalytic current density of 10 mA cm-2 in 1 m PBS and 50 mA cm-2 in 1
      m KOH for 10 h, respectively.

PMID- 30238678
TI  - The illusion of choice: an exploratory study looking at the top 10 food companies
      in Australia and their brand connections.
AB  - OBJECTIVE: To identify the brands owned by each of the 10 top grossing food
      companies operating in Australia and visually represent them on an infographic.
      METHODS: Desktop research was conducted to determine Australia's 10 largest food
      companies based on revenue. Brand ownership for each of the companies was traced
      through financial records and company publications. This information was then
      visually documented in the form of an infographic 'food web' to clearly
      illustrate company and brand ownership. RESULTS: Fonterra, Coca-Cola Amatil,
      Lion, Murray Goulburn, George Weston Foods, Wilmar, Nestle, Mondelez, Parmalat
      and Asahi were determined as the top 10 food companies operating in Australia.
      The food web illustrated that brand ownership ranged from 75 (Nestle) to four
      (Fonterra) brands per company. CONCLUSIONS: The food web illustrates the
      dominance of each of these major companies within Australia and shows how their
      diverse brand ownership limits consumer choice. Implications for public health:
      This study expands on current knowledge and further defines the breadth of market
      influence that the top 10 food companies have within the Australian food context,
      and how they use their brand power to create an illusion of choice for consumers.
      The food web will assist in promoting transparency of brand ownership in the
      Australian food market, therefore allowing consumers to make an informed decision
      about the food they purchase, and will allow community and other organisations to
      make an informed decision about which companies they form partnerships with.

PMID- 30238680
TI  - Label-Free Detection of Protein Tyrosine Phosphatase 1B (PTP1B) by Using a
      Rationally Designed Forster Resonance Energy Transfer (FRET) Probe.
AB  - A highly selective detection method of native protein tyrosine phosphatase 1B
      (PTP1B) is described using a target specific probe equipped with 1-naphthylamine
      (lambdaex =330 nm, lambdaem =445 nm). Irradiation of a mixture of PTP1B and Probe
      1 with ultraviolet light of 280 nm (corresponding to PTP1B excitation maximum)
      resulted in significant fluorescence increase at 445 nm, following FRET
      characteristics. This phenomenon does not occur with other closely related
      phosphatases or cellular abundant alkaline phosphatase (APP). Probe 1, the most
      potent and selective probe, was found to competitively inhibit PTP1B (Ki ~42 nm),
      whereas APP inhibition was found to be in the low micromolar range. Furthermore,
      Probe 1 discriminates between PTP1B and several other phosphatases. Here, we
      report real-time label-free FRET detection of pure PTP1B as well as induced human
      PTP1B in Escherichia coli cell lysate. In contrast to 6,8-difluoro-4
      methylumbelliferyl phosphate (DiFMUP), a representative fluorescence turn-on PTP
      substrate, our FRET probe successfully differentiated human cervical carcinoma
      cell lysate, SiHa, which has a high expression level of PTP1B, from PTP1B
      knockdown SiHa cell lysate (that is, siRNA was used for PTP1B knockdown).

PMID- 30238679
TI  - Population pharmacokinetics of extended-release levetiracetam in epileptic dogs
      when administered alone, with phenobarbital or zonisamide.
AB  - BACKGROUND: Extended-release levetiracetam (LEV-XR) has gained acceptance as an
      antiepileptic drug in dogs. No studies have evaluated its disposition in dogs
      with epilepsy. HYPOTHESIS/OBJECTIVES: To evaluate the pharmacokinetics of LEV-XR
      in epileptic dogs when administered alone or with phenobarbital or zonisamide.
      ANIMALS: Eighteen client-owned dogs on steady-state maintenance treatment with
      LEV-XR (Group L, n = 6), LEV-XR and phenobarbital (Group LP, n = 6), or LEV-XR
      and zonisamide (Group LZ, n = 6). METHODS: Pharmacokinetic study. Blood samples
      were collected at 0, 2, 4, 8, and 12 hours after LEV-XR was administered with
      food. Plasma LEV concentrations were determined by high-pressure liquid
      chromatography. A population pharmacokinetic approach and nonlinear mixed effects
      modeling were used to analyze the data. RESULTS: Treatment group accounted for
      most of the interindividual variation. The LP group had lower CMAX (13.38 MUg/mL)
      compared to the L group (33.01 MUg/mL) and LZ group (34.13 MUg/mL), lower AUC
      (134.86 versus 352.95 and 452.76 hours.MUg/mL, respectively), and higher CL/F
      (0.17 versus 0.08 and 0.07 L/kg/hr, respectively). The half-life that defined the
      terminal slope of the plasma concentration versus time curve (~5 hours) was
      similar to values previously reported for healthy dogs. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Considerable variation exists in the pharmacokinetics of LEV-XR in
      dogs with epilepsy being treated with a common dose regimen. Concurrent
      administration of phenobarbital contributed significantly to the variation. Other
      factors evaluated, including co-administration of zonisamide, were not shown to
      contribute to the variability. Drug monitoring may be beneficial to determine the
      most appropriate dose of LEV-XR in individual dogs.

PMID- 30238681
TI  - Nickel, Cobalt and Palladium Catalysed C-H Functionalization of Un-activated
      C(sp3 )-H Bond.
AB  - This review represents nickel, cobalt and palladium catalyzed C-H activation of
      sp3 carbon, with special emphasis on methyl C-H activation. The importance of
      directing group assistance and effect of ligand on beta- or gamma- C(sp3 )-H
      activation is summarized in this review. The mechanistic study for Ni, Co and Pd
      catalyzed sp3 C-H bond functionalization also discussed in detail.

PMID- 30238682
TI  - Access to Abortion in Central Appalachian States: Examining County of Residence
      and County-Level Attributes.
AB  - CONTEXT: Studies of how women's individual characteristics and place of residence
      are related to variability in gestational age at the time of abortion have not
      examined county of residence and county-level characteristics. The county level
      is potentially meaningful, given that county is the smallest geographic unit with
      policy implications. METHODS: Data on 38,611 abortions that took place in North
      Carolina, Virginia and West Virginia in 2012 were used to study the relationship
      between gestational age and county-level attributes (e.g., metropolitan status
      and poverty). Three-level hierarchical linear models captured individuals nested
      in county of residence, clustered by state of residence, and adjusted for
      individual characteristics and distance traveled to care. RESULTS: Eight percent
      of the variation in gestational age at abortion was attributable to county-level
      characteristics. Residents of counties characterized by persistent poverty
      obtained abortions 2.3 days later in gestation than those from counties not
      characterized by that level of economic hardship. Women living in nonmetropolitan
      counties obtained abortions 1.7 days later than those living in metropolitan
      counties, even after distance traveled and county-level poverty were controlled
      for. CONCLUSION: County of residence is relevant to gestational age at the time
      of abortion for women in these three states. Evidence that county-level
      attributes are related to access adds insight to the consequences for women when
      the landscape of abortion service delivery shifts. Integrating county of
      residence into research on access to abortion services may be critical to
      capturing disparities in access.

PMID- 30238683
TI  - Pseudoexfoliation and aortic aneurysm: a long-term follow-up study.
AB  - PURPOSE: To study the relationship between pseudoexfoliation (PEX) and aortic
      aneurysm in a population with a high prevalence of PEX. METHODS: Survival
      analyses were performed in a cohort of 735 residents aged 65-74 years, examined
      in a population survey in the municipality of Tierp, Sweden, 1984-1986. To expand
      the sample size, 1040 people were recruited by means of glaucoma case records
      established at the Eye Department in Tierp in 1978-2007. In this way, the cohort
      comprised 1775 subjects, representing more than 25 400 person-years at risk.
      Medical records and autopsy reports were reviewed to identify subjects diagnosed
      with aneurysm. Those with a follow-up time shorter than 1 year were excluded.
      RESULTS: By the end of the study in September 2017, 60 new cases of aortic
      aneurysm had been found. Of these cases, 23% (14 subjects) were affected by PEX
      at baseline, compared with 28% among subjects without aneurysm. No association
      between PEX and aortic aneurysm was found (hazard ratio 0.97; 95% confidence
      interval 0.53-1.77). CONCLUSION: In this population-based study, we were unable
      to verify a relationship between PEX and the development of aortic aneurysm.

PMID- 30238684
TI  - Online referral and immediate appointment selection system empowers families and
      improves access to public community paediatric clinics.
AB  - AIM: We aimed to introduce a low-cost combined online referral and immediate
      appointment selection system (CORIAS) to empower referrers and parents by
      allowing them to schedule an appointment at a time and location of their choosing
      in conjunction with the referrer at the time of referral. This was because an
      unacceptably high rate of reported lost referrals, combined with a high rate of
      failure to attend initial appointments (FTAs), was noted at a six-site community
      paediatric clinic service. We aimed to analyse the impact of CORIAS on important
      outcomes including timely appointment scheduling, attendance, loss of referrals,
      user acceptance, overall cost and administrative burden. METHODS: For 3-month
      periods before and after the implementation of CORIAS, data were collected
      regarding all new referrals received and initial appointments scheduled, as well
      as reports of lost referrals. The number of attended initial appointments, FTAs,
      failures in successfully scheduling appointments, referrer background, CORIAS
      cost and qualitative feedback received from relevant parties was collated and
      analysed. RESULTS: The proportion of referrals reported lost was 6% following the
      implementation of the combined online system in comparison to 17% pre
      implementation. The FTA rate for scheduled initial appointments pre
      implementation was 16%; post-implementation, the FTA rate was 9%. Qualitative
      benefits included a decrease in the administrative burden associated with
      appointment scheduling and increased service access for culturally and
      linguistically diverse families. CONCLUSION: Appropriately designed and
      implemented novel online systems may improve timely and equitable access to
      health care by providing secure, reliable pathways for referrers and by
      empowering and improving communication with patients and families.

PMID- 30238685
TI  - MicroRNA-27a mediates the Wnt/beta-catenin pathway to affect the myocardial
      fibrosis in rats with chronic heart failure.
AB  - OBJECTIVE: To clarify the influence of MicroRNA-27a (miR-27a)-mediated Wnt/beta
      catenin pathway on the myocardial fibrosis in rats with chronic heart failure
      (CHF). METHODS: The CHF rat models were constructed and randomly divided into
      four groups (Sham, Model, AntagomiR-27a, and NC antagomiR-27a groups).
      Echocardiography was used to test the cardiac function indexes, HE (haematoxylin
      eosin) staining to observe the pathological injury of myocardium, Masson staining
      to analyze the collagen volume fraction (CVF), and qRT-PCR (quantitative real
      time PCR) and Western blotting to detect the expressions of miR-27a and Wnt/beta
      catenin pathway-related proteins. Besides, cardiomyocytes were isolated and
      transfected with miR-27a mimic or miR-27a inhibitor to detect the expressions of
      Wnt/beta-catenin pathway. RESULTS: The CHF rats were significantly increased in
      LVESD (left ventricular end systolic diameter) and LVEDD (left ventricular end
      diastolic diameter), and clearly reduced in FS (fractional shortening) and EF
      (left ventricular ejection fraction) (all P < 0.05). Moreover, LVWI (left
      ventricular mass index) and CVF (Collagen Volume Fraction), type I and type III
      collagen, and the ratio of type I/III collagen, as well as the expression of miR
      27a, TGF-beta1 and p-Smad2/3, beta-catenin, p-GSK-3beta and alpha-SMA were also
      elevated (all P < 0.05). Additionally, the CHF rats treated with AntagomiR-27a
      were improved in these indexes, and the expression of miR-27a and Wnt/beta
      catenin pathway was significantly inhibited (all P < 0.05). Furthermore,
      cardiomyocytes transfected with miR-27a inhibitor significantly decreased the
      levels of miR-27a and Wnt/beta-catenin pathway (all P < 0.05). CONCLUSION: Down
      regulation of miR-27a may inhibit the Wnt/beta-catenin pathway to reduce the
      deposition of myocardial collagen, prevent myocardial fibrosis and improve
      cardiac function. This article is protected by copyright. All rights reserved.

PMID- 30238686
TI  - House sparrows (Passer domesticus) adjusted hypothalamic-pituitary-adrenal axis
      negative feedback and perch hopping activities in response to a single repeated
      stimulus.
AB  - Chronic stress has been extensively studied in both laboratory and field
      settings; however, a conclusive and consistent phenotype has not been reached.
      Several studies have reported attenuation of the hypothalamic-pituitary-adrenal
      axis during experiments intended to cause chronic stress. We sought to determine
      whether this attenuation could be indicative of habituation. Importantly, we were
      not investigating habituation to a specific stimulus-as many stress physiology
      studies do-but rather we assessed how the underlying physiology and behavior
      changed in response to repeated stressor presentation. We exposed house sparrows
      (Passer domesticus) to a single stimulus twice per day at random times for 8
      consecutive days. We predicted that this period of time would be long enough for
      the birds to determine that these acute stressors were not, in fact, dangerous
      and they would, therefore, acclimate. A second control group remained undisturbed
      for the same period of time. We measured baseline, stress-induced, negative
      feedback strength, and maximum production of corticosterone as well as neophobic
      behavior before, during, and after this 8-day experiment. When birds experienced
      a stimulus for 4 days, their negative feedback strength was significantly
      diminished, but recovered after the second 4 days. Additionally, perch hopping
      decreased and recovered in this same time frame. These data suggest that distinct
      physiological and behavioral responses arise when house sparrows are exposed to
      the same stressor for several consecutive days as opposed to many stressors
      layered on top of one another. Furthermore, they indicate that habituation-as
      with chronic stress-can appear differently depending on the metric being
      examined.

PMID- 30238688
TI  - Robotic single-site myomectomy: A single-center experience of 101 consecutive
      cases.
AB  - BACKGROUND: To evaluate the feasibility and clinical outcomes of robotic single
      site myomectomy (RSSM) for uterine myoma. METHODS: Medical records of 101
      consecutive women who underwent RSSM were retrospectively reviewed, and patient
      characteristics and surgical outcomes were evaluated. The surgical outcomes were
      compared by the phase in learning curve (early phase of <10 cases vs late phase
      of >=10 cases) and time flow. RESULTS: A total of 47 (46.5%) women had multiple
      myomas, and a median two (1-12) myomas were retrieved. The largest myoma was
      averagely measured as 6.2 +/- 1.7 cm, and the mean weight of the total retrieved
      myomas was 114.0 +/- 84.4 g. No patients received a transfusion or had operation
      related complications. Cases in the late phase showed shorter port placement time
      and docking time than those in the early phase. CONCLUSIONS: Our data suggest
      that robotic single-site surgery is a feasible therapeutic option for uterine
      myoma.

PMID- 30238687
TI  - Androgen-responsive tripartite motif 36 enhances tumor-suppressive effect by
      regulating apoptosis-related pathway in prostate cancer.
AB  - Tripartite motif 36 (TRIM36) belongs to the TRIM family, most members of which
      are involved in ubiquitination and degradation of target proteins by functioning
      as E3 ubiquitin ligases. The function of TRIM36 has not been well documented,
      therefore, we investigated the clinical significance and function of TRIM36 in
      human prostate cancer (PC). Multivariate logistic regression analysis showed that
      TRIM36 immunoreactivity was an independent predictor of cancer-specific survival
      of PC patients. Gain-of-function study revealed that overexpression of TRIM36
      suppressed cell proliferation and migration of LNCaP, 22Rv1, and DU145 cells.
      Moreover, TRIM36 knockdown using siRNA suppressed apoptosis and promoted cell
      proliferation and migration in LNCaP and 22Rv1 cells. Furthermore, our microarray
      analysis revealed that the apoptosis-related pathway was significantly
      upregulated by TRIM36 overexpression. The TUNEL assay showed that apoptosis
      promoted by docetaxel treatment was alleviated in siTRIM36-treated LNCaP and
      22Rv1 cells. Taken together, these results suggest that high expression of TRIM36
      is associated with favorable prognosis and that TRIM36 plays a tumor-suppressive
      role by inhibiting cell proliferation and migration as well as promoting
      apoptosis in PC.

PMID- 30238689
TI  - Heterogeneous Nucleation onto Monoatomic Ions: Support for the Kelvin-Thomson
      Theory.
AB  - In this study, the process of heterogeneous nucleation is investigated by
      coupling a high-resolution differential mobility analyser (DMA) to an expansion
      type condensation particle counter, the size-analyzing nuclei counter (SANC).
      More specifically, we measured the activation probabilities of monoatomic ions of
      both polarities by using n-butanol as condensing liquid. All seed ions were
      activated to grow into macroscopic sizes at saturation ratios well below the
      onset of homogeneous nucleation, showing for the first time that the SANC is
      capable of detecting sub-nanometer sized, atomic seed ions. The measured onset
      saturation ratios for each ion were compared to the Kelvin-Thomson (KT) theory.
      Despite the fact that certain dependencies of activation behaviour on seed ion
      properties cannot be predicted by the KT theory, it was found that with a simple
      adjustment of the n-butanol molecular volume (9-15 % lower compared to bulk
      properties) good agreement with experimental results is achievable. The
      corresponding density increase may result from the dipole-charge interaction.
      This study thus offers support for the application of the KT model for
      heterogeneous, ion-induced nucleation studies at the sub-nanometer level.

PMID- 30238690
TI  - The effect of bariatric surgery on intraocular pressure.
AB  - PURPOSE: Study purpose was to investigate the effects of bariatric surgery on
      intraocular pressure (IOP) and other ophthalmic parameters in a prospective
      observational follow-up study. METHODS: Ophthalmic examination was performed on
      22 obese women before and 6 months after bariatric surgery. A control group of 15
      non-obese age-matched women were studied twice 6 months apart. IOP was measured
      with the Goldmann applanation tonometer (GAT) and the Pascal dynamic contour
      tonometer (PDCT). None of the subjects had glaucoma. RESULTS: Average weight loss
      6 months after bariatric surgery was 25 +/-8 kg, (p < 0.05). Visual acuity (VA),
      pachymetry and systolic as well as diastolic blood pressures did not differ
      between the obese and control groups and no change between the visits was
      detected. At baseline, IOP was significantly higher in the obese group than in
      the controls (16.6 +/- 3.0 mmHg GAT and 18.1 +/- 2.2 mmHg PDCT compared with 14.3
      +/- 1.5 mmHg GAT and 16.5 +/- 1.9 mmHg PDCT respectively). After bariatric
      surgery, IOP was significantly lower (15.2 +/- 2.7 mmHg GAT and 16.5 +/- 2.0 mmHg
      PDCT, p < 0.05) and no significant difference was detected between the operated
      and control groups. In the whole data at baseline, IOP correlated with weight,
      body mass index, waist circumference, body fat per cent and systolic blood
      pressure values. CONCLUSION: Intraocular pressure (IOP) is significantly higher
      in obese women than in non-obese age-matched controls. Obese subjects had a
      decrease in IOP after bariatric surgery with no change in IOP in the control
      group. This change in obese group may be related to weight loss. Different
      measures of obesity correlated with IOP at baseline.

PMID- 30238691
TI  - Fluorinated Acid-Labile Branched Hydroxyl-Rich Nanosystems for Flexible and
      Robust Delivery of Plasmids.
AB  - Nucleic acid-based therapy specially needs a safe and robust delivery vector.
      Herein, a novel fluorinated acid-labile branched hydroxyl-rich polycation (ARP-F)
      is proposed for the flexible and effective delivery nanovector of different
      plasmids including reporter genes and the Cas9 plasmid. Acid-responsive
      polycation (ARP) with plentiful ortho ester linkages and hydroxyl groups is first
      synthesized via a facile one-pot ring-opening polymerization, followed by
      decoration of fluorinated alkyl chains onto ARP to achieve ARP-F. ARP-F possesses
      good pH-responsive degradability, biocompatibility, and its preliminary
      transfection ability evaluated by reporter plasmids pRL-CMV (encoding Renilla
      luciferase) and pEGFP-N1 (encoding enhanced green fluorescent protein) is also
      excellent. CRISPR-Cas9 (clustered regularly interspaced short palindromic
      repeat/CRISPR-associated nuclease 9) technology is a potent genome-editing tool.
      The subsequent delivery of pCas9-surv (one typical all-in-one Cas9 plasmid)
      mediated by ARP-F exhibits impressive in vitro and in vivo tumor inhibition
      performances. In addition, the combination of ARP-F/pCas9-surv with temozolomide
      could further enhance tumor inhibition activities by increasing the sensitivity
      of cancer cells to anticancer drugs. Such high-performance polycation would
      provide a very promising means to produce efficient delivery nanovectors of
      versatile plasmids.

PMID- 30238693
TI  - Upcoming events of interest.

PMID- 30238694
TI  - Cerebral Venous Thrombosis in Spontaneous Intracranial Hypotension: A Report on 4
      Cases and a Review of the Literature.
AB  - OBJECTIVE: Spontaneous intracranial hypotension is a risk factor for cerebral
      venous thrombosis. The occurrence of cerebral venous thrombosis in patients with
      spontaneous intracranial hypotension raises difficult practical questions
      regarding the management of the 2 conditions. We reviewed our experience and the
      relevant literature to evaluate these related questions. METHODS: We
      retrospectively studied the medical records and imaging studies of patients with
      spontaneous intracranial hypotension at a tertiary center from January 2007
      through January 2017. The main search strategy was a literature review of journal
      articles in PubMed (1966 to January 2017). RESULTS: Among 374 patients with
      spontaneous intracranial hypotension, 4 were also diagnosed with cerebral venous
      thrombosis. A literature review yielded an additional 31 cases, including 21 men
      and 14 women with a mean age of 40.6 years. Of the 35 patients, 8 (22.8%)
      patients received anticoagulation therapy and epidural blood patch. Nineteen
      (54.3%) patients were given anticoagulant only. Seven (20%) patients were treated
      with epidural blood patch only. One (2.9%) patient did not receive epidural blood
      patch or anticoagulation therapy. There is no difference in terms of age, sex,
      diagnosis interval, association with other complications, and prognosis between
      the first 3 groups. Of the 19 patients who received anticoagulation therapy, 4
      patients (21.1%) had intracranial hemorrhage or hematoma enlargement after
      anticoagulation, and one of these 4 patients died following further intracranial
      hemorrhage. Of the 8 patients who received both anticoagulation and epidural
      blood patch, 1 patient (12.5%, P = 0.528) developed subdural hematoma after
      anticoagulation. Of the 5 cases had intracranial hemorrhage aggravation after
      anticoagulation, 4 were subdural hematoma occurrence or enlargement. CONCLUSION:
      Cerebral venous thrombosis is a rare but important complication of spontaneous
      intracranial hypotension. The primary focus of treatment should be the treatment
      of intracranial hypotension. It could be possible that anticoagulation might
      increase the risk of intracranial hemorrhage in patients with spontaneous
      intracranial hypotension, although a firm conclusion could not be drawn based on
      the limited number of patients currently available. The use of anticoagulation
      therapy should be prudent and should be monitored carefully if initiated.

PMID- 30238692
TI  - The impact of sedentarism on heart rate variability (HRV) at rest and in response
      to mental stress in young women.
AB  - Sedentarism is one of the main risk factors for the onset of cardiometabolic
      diseases. Some biomarkers, such as heart rate variability (HRV), have been
      largely studied and found to be involved in the genesis of the dysfunctions
      associated with sedentary behavior. However, comparatively few studies have
      focused on the female sex. The objective of this study was to analyze the
      hemodynamic, autonomic and quality of life parameters at rest and in response to
      mental stress of sedentary and physically active young women. A total of 96
      women, 18-30 years of age, were divided into sedentary (SW = 48) and active (AW =
      48) groups. Anthropometric, hemodynamic and quality of life parameters were
      evaluated and the R-R interval was recorded to quantify the cardiac autonomic
      modulation at rest and in response to the Stroop Color Test. The groups were
      similar in age, weight, height, body mass index, fat percentage, systolic and
      diastolic blood pressure values and glycemia. The physical health domain of
      quality of life was compromised in the SW group. The SW group presented higher
      heart rate, lower variance of RR interval and RMSSD and higher cardiac
      sympathovagal balance (LF/HF) both at rest and in response to the mental stress
      test. We concluded that sedentary lifestyle in women induces impairment in
      autonomic cardiac modulation at rest and in response to physiological stress,
      compromising the quality of life, even before altering any cardiovascular or
      metabolic clinical parameters, reinforcing the potential role of HRV as early
      marker of cardiovascular risk in this population.

PMID- 30238695
TI  - An investigation of the quality of pretend play ability in children with cerebral
      palsy.
AB  - BACKGROUND: Cerebral palsy (CP) describes a group of permanent disorders in the
      development of movement and posture due to non-progressive disturbances during
      foetal or infant brain development that can result in activity limitations,
      including engagement in pretend play. METHODS: Twenty children aged four to seven
      years with spastic CP participated in this descriptive qualitative study. The
      Child-Initiated Pretend Play Assessment (ChIPPA) clinical observations were
      analysed from five categories: Time, Interaction with the examiner, Imitation,
      Theme and Story. RESULTS: Seventy per cent (70%) of the children completed the
      assessment (Time), and 90% of children interacted socially with the examiner
      during the play (Interaction with the examiner). All children initiated their
      pretend play without requiring examiner demonstration (Imitation). Sixty per cent
      (60%) of the children were appropriate to their stage of development for Theme.
      Finally, 60% of the children set up a scenario, but did not develop a narrative
      (Story). CONCLUSION: Qualitative aspects of the children's pretend play
      performance were satisfactory, showing typical play indicators in all the
      categories, except for 'Story'. 'Story' represents more complexity in a child's
      pretend play ability. Therefore, a play intervention is suggested to stimulate
      and expand the pretend play ability of preschool children with CP.

PMID- 30238696
TI  - Bioanalytical method development and validation of moxidectin in plasma by LC
      MS/MS: Application to in vitro metabolism.
AB  - Moxidectin (MOX) has recently been approved by the US Food and Drug
      Administration for the treatment of river blindness in select populations. It is
      also being evaluated as an alternative for the use of ivermectin, widespread
      resistance to which is becoming a global health issue. Moreover, MOX is becoming
      increasingly used as a prophylactic antiparasitic in the cattle industry. In this
      study, we developed and validated an LC-MS/MS method of MOX in human, monkey and
      mouse plasma. The separation was achieved on an ACE C18 (50 * 3.0 mm, 3 MUm)
      column with isocratic elution using 0.1% acetic acid and methanol-acetonitrile
      (1:1, v/v) as mobile phase. MOX was quantitated using MS/MS with an electrospray
      ionization source operating in negative multiple reaction monitoring mode. The
      multiple reaction monitoring precursor ion -> product ion transitions for MOX and
      abamectin (IS) were m/z 638.40 -> 236.30 and m/z 871.50 -> 565.35 respectively.
      The MS/MS response was linear over the concentration range 0.1-1000 ng/mL in
      plasma with a correlation coefficient (r2 ) of 0.997 or better. The within- and
      between-day precision (relative standard deviation, RSD) and accuracy were within
      the acceptable limits per US Food and Drug Administration guidelines. The method
      was successfully applied to an in vitro metabolic stability study of MOX.

PMID- 30238698
TI  - Polymer Synthesis with More Than One Form of Living Polymerization Method.
AB  - Controlled radical polymerization (CRP) or controlled/living radical
      polymerization has revolutionized the polymer industry as a tool for the
      preparation of a wide variety of polymers. This process enables the preparation
      of polymers with good control of molecular weight, narrow polydispersity, and a
      range of architectures including block and graft copolymers, star polymers, and
      other functional polymers. The mechanistic transformation reaction provides a
      great opportunity to tune chemical and physical properties of copolymers. It can
      be applied to combine different homopolymers using post-modification techniques
      or by the use of a dual initiator, allowing the combination of mechanistically
      distinct polymerization reactions. This review will cover CRP transformations
      including the synthesis of block copolymers with both linear structures (AB, ABA,
      (AB) n , multiblocks, etc.) and branched macromolecular architectures (graft,
      miktoarm star, and dendritic-like), which are obtained by a combination of more
      than one form of living polymerization reaction.

PMID- 30238697
TI  - Comparison of the mitral valve morphologies of Cavalier King Charles Spaniels and
      dogs of other breeds using 3D transthoracic echocardiography.
AB  - BACKGROUND: Myxomatous mitral valve disease (MMVD) is more prevalent in Cavalier
      King Charles Spaniels (CKCSs) compared to dogs of other breeds at a given age.
      Abnormal valvular stress is thought to contribute to the development and
      progression of MMVD, and a relationship exists between mitral valve (MV)
      morphology and stress acting on the valve. OBJECTIVES: To determine whether the
      MV morphology of healthy adult CKCSs differs from the morphology of healthy adult
      dogs of other breeds determined by RT-3DTTE. ANIMALS: Thirty-five healthy CKCSs
      and 41 healthy dogs of other breeds. METHODS: Prospective cross-sectional study.
      Dogs underwent physical examination, conventional echocardiography, and RT-3DTTE.
      RT-3DTTE datasets were analyzed using dedicated software for MV morphologic
      analysis. Morphologic variables were compared between CKCSs and dogs of other
      breeds. RESULTS: The MV of healthy CKCSs had a smaller annulus height (0.46 +/-
      0.11 vs. 0.56 +/- 0.17; P = .0021), tenting height (0.26 +/- 0.12 vs. 0.42 +/-
      0.18; P < .001), tenting area (0.42 +/- 0.15 vs. 0.79 +/- 0.34; P < .001),
      normalized tenting volume (0.09 [0.05-0.13] vs. 0.14 [0.10-0.20]; P < .001), and
      normalized area of the posterior leaflet (0.57 +/- 0.15 vs. 0.66 +/- 0.18; P =
      .016) compared to healthy dogs of other breeds; this results in CKCSs having a
      flatter MV with reduced tenting, compared to the MV of other breeds. CONCLUSIONS
      AND CLINICAL IMPORTANCE: These morphologic features could confer a mechanical
      disadvantage and play a role in the predisposition of CKCSs to the early
      development of MMVD.

PMID- 30238700
TI  - Visible Light Actuated Efficient Exclusion Between Plasmonic Ag/AgCl Micromotors
      and Passive Beads.
AB  - Insight is provided into the collective behavior of visible-light photochemically
      driven plasmonic Ag/AgCl Janus particles surrounded by passive polystyrene (PS)
      beads. The active diffusion of single Janus particles and their clusters (small:
      consisting of two or three Janus particles and large: consisting of more than ten
      Janus particles), and their interaction with passive PS beads, are analyzed
      experimentally and in simulations. The diffusivity of active Janus particles, and
      thus the exclusive effect to passive PS beads, can be regulated by the number of
      single Janus particles in the cluster. On the simulation side, the Langevin
      equations of motion for self-propelled Janus particles and diffusing passive PS
      beads are numerically solved using Molecular-Dynamics simulations. The complex
      interactions of both subsystems, including elastic core-to-core interactions,
      short-range attraction, and effective repulsion due to light-induced chemical
      reactions are considered. This complex mixed system not only provides insight to
      the interactive effect between active visible light-driven self-propelled
      micromotors and passive beads, but also offers promise for implications in light
      controlled propulsion transport and chemical sensing.

PMID- 30238701
TI  - Well-being loss in informal care for the elderly people: Empirical study from
      China national baseline CHARLS.
AB  - INTRODUCTION: Well-being is an important component of health, while informal care
      plays a vital role in daily care of the elderly. However, the effects of informal
      care on the well-being of the elderly remain unclear. This study was aimed to
      estimate such effects, in which well-being was measured by 2 subjective
      indicators: happiness and life satisfaction. METHODS: Potential endogeneity was
      purified using instrumental variables. Data were collected from national baseline
      China Health and Retirement Longitudinal Study (CHARLS). RESULTS: Receiving
      informal care would decrease the elderly's happiness score and life satisfaction
      score significantly. The health produced from informal care cannot offset the
      health depreciation caused by aging. DISCUSSION: To improve the well-being of the
      elderly, caregivers have more to do and policymakers can design designated care
      policies based on our results.

PMID- 30238702
TI  - Respiratory symptoms associated with eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is an atopic condition diagnosed based on
      eosinophilic infiltration in the esophagus and symptoms of esophageal
      dysfunction. Typical clinical manifestations of EoE include feeding refusal,
      vomiting, and dysphagia however recent reports highlight an associations with
      extraesophageal symptoms. By definition the inflammatory response in EoE is
      restricted to the esophagus. However, accounts of symptoms such as chronic
      refractory cough, recurrent croup, hoarseness as well as subglottic stenosis, and
      an increase in otolaryngologic surgeries in patients with EoE raise the
      possibility of extraesophageal manifestations of the disease. These symptoms have
      been reported at times in the absence of typical gastrointestinal symptoms. While
      the condition is usually managed by gastroenterologist and/or allergist, the
      presence of extraesophageal symptoms and comorbid conditions may result in
      patients presenting initially to providers in other subspecialties such as
      pulmonology and otorhinolaryngology. The use of proton pump inhibitors and
      corticosteroids are part of the management of EoE. Awareness of the possibility
      of EoE before the empiric use of these therapies is important as there use can
      make identifying and diagnosing patients with EoE correctly challenging. We
      review the medical literature regarding extraesophageal manifestations of EoE and
      highlight the importance of awareness for subspecialist outside of
      gastroenterology and allergy for the condition.

PMID- 30238699
TI  - The role of sphingosine-1-phosphate in inflammation and cancer progression.
AB  - Many inflammatory mediators are involved in the process of carcinogenesis and
      cancer progression. In addition to cytokines and chemokines, lipid mediators have
      recently attracted attention as signaling molecules associated with inflammatory
      diseases. Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that
      regulates cell survival and migration, immune cell recruitment, angiogenesis and
      lymphangiogenesis. S1P also plays a significant role in inflammation and cancer.
      The gradation of S1P concentration in the blood, lymph and tissue regulates
      lymphocyte trafficking, an important component of inflammation. Furthermore,
      cancer cells produce elevated levels of S1P, contributing to the tumor
      microenvironment and linking cancer and inflammation. Future technological
      advances may reveal greater detail about the mechanisms of S1P regulation in the
      tumor microenvironment and the contribution of S1P to cancer progression.
      Considering the critical role of S1P in linking inflammation and cancer, it is
      possible that the S1P signaling pathway could be a novel therapeutic target for
      cancers with chronic inflammation.

PMID- 30238703
TI  - Thermal imaging and planimetry evaluation of the results of chronic wounds
      treatment with hyperbaric oxygen therapy.
AB  - BACKGROUND: One of the methods to treat chronic wounds is the use of hyperbaric
      oxygen (HBO). Objective measurement of the wound surface is an important element
      in the process of monitoring and predicting the progress of treatment.
      OBJECTIVES: The aim of the study was to evaluate the effect of hyperbaric oxygen
      therapy (HBOT) on ulcer wound healing in patients with chronic venous
      insufficiency ulcers and diabetic foot syndrome using thermal imaging and
      computerized planimetry. MATERIAL AND METHODS: During a 3-year period, 284
      digital computer planimetry measurements were gathered from 142 patients treated
      for leg ulcers caused by chronic venous insufficiency and ulcers from diabetic
      foot syndrome at HBOT Unit of the Dr Stanislaw Sakiel Centre for Burns Treatment
      in Siemianowice Slaskie (Poland). Each patient took 30 HBOT sessions using a Haux
      multiplace HBO chamber at a pressure of 2.5 atmospheres absolute (ATA). The
      results of the treatment were monitored by thermovision and computerassisted
      planimetry measurements performed before and after HBOT. RESULTS: Both groups of
      patients exhibited a reduction in the surface and perimeter of the wound after
      HBOT. The treatment effects were also confirmed by thermal imaging. The areas
      calculated from thermal imaging and planimetry are different but correlated.
      CONCLUSIONS: It seems that a combination of thermal imaging and planimetry may
      enhance the diagnosis as well as provide the physician with more information
      about therapy effects.

PMID- 30238704
TI  - De-Escalation of P2Y12 Receptor Inhibitor Therapy after Acute Coronary Syndromes
      in Patients Undergoing Percutaneous Coronary Intervention.
AB  - Dual antiplatelet therapy (DAPT) - a combination of a P2Y12 receptor inhibitor
      and aspirin - has revolutionized antithrombotic treatment. Potent P2Y12
      inhibitors such as prasugrel and ticagrelor exhibit a strong and more consistent
      platelet inhibition when compared to clopidogrel. Therefore, ticagrelor and
      prasugrel significantly reduce ischemic events, but at an expense of an increased
      bleeding risk in acute coronary syndrome (ACS) patients undergoing percutaneous
      coronary intervention (PCI). These observations have engaged intensive clinical
      research in alternative DAPT regimens to achieve sufficient platelet inhibition
      with an acceptable bleeding risk. Our review focusses on P2Y12 receptor therapy
      de-escalation defined as a switch from a potent antiplatelet agent (ticagrelor or
      prasugrel) to clopidogrel. Recently, both unguided (platelet function testing
      independent) and guided (platelet function testing dependent) DAPT de-escalation
      strategies have been investigated in different clinical studies and both
      switching strategies could be possible options to prevent bleeding complications
      without increasing ischemic risk. In light of the still limited data currently
      available, future large-scale trials should accumulate more data on various DAPT
      de-escalation regimens with both ticagrelor and prasugrel in unguided and guided
      de-escalation approaches. In the current review we aim at summarizing and
      discussing the current evidence on this still emerging topic in the field of
      antiplatelet treatment.

PMID- 30238708
TI  - Ergonovine Provocation Echocardiography for Detection and Prognostication in
      Patients with Vasospastic Angina.

PMID- 30238705
TI  - Anticoagulation for Stroke Prevention in Older Adults with Atrial Fibrillation
      and Comorbidity: Current Evidence and Treatment Challenges.
AB  - The burden of atrial fibrillation (AF) is projected to increase substantially
      over the next decade in parallel with the aging of the population. The increasing
      age, level of comorbidity, and polypharmacy will complicate the treatment of
      older adults with AF. For instance, advanced age and chronic kidney disease have
      been shown to increase the risk of both thromboembolism and bleeding in patients
      with AF. Frailty, recurrent falls and polypharmacy, while very common among
      elderly patients with AF, are often overlooked in the clinical decision making
      despite their significant interaction with oral anticoagulant (OAC) and profound
      impact on the patient's clinical outcomes. Such factors should be recognized,
      evaluated and considered in a comprehensive decision-making process. The
      introduction of non-vitamin K oral anticoagulants has radically changed the
      management of AF allowing for a more individualized selection of OAC. An
      understanding of the available data regarding the performance of each of the
      available OAC in a variety of at risk patient populations is paramount for the
      safe and effective management of this patient population. The aim of this review
      is to appraise the current evidence, point out the gaps in knowledge, and provide
      recommendations regarding stroke prevention in older adults with AF and comorbid
      conditions.

PMID- 30238707
TI  - Ergonovine Stress Echocardiography for the Diagnosis of Vasospastic Angina and
      Its Prognostic Implications in 3,094 Consecutive Patients.
AB  - BACKGROUND AND OBJECTIVES: Ergonovine stress echocardiography (ErgECHO) has been
      proposed as a noninvasive tool for the diagnosis of coronary vasospasm. However,
      concern over the safety of ErgECHO remains. This study was undertaken to
      investigate the safety and prognostic value of ErgECHO in a large population.
      METHODS: We studied 3,094 consecutive patients from a single-center registry who
      underwent ErgECHO from November 2002 to June 2009. Medical records,
      echocardiographic data, and laboratory findings obtained from follow-up periods
      were analyzed. RESULTS: The overall positive rate of ErgECHO was 8.6%. No
      procedure-related mortality or myocardial infarction (MI) occurred. Nineteen
      patients (0.6%) had transient symptomatic complications during ErgECHO including
      one who was successfully resuscitated. Cumulative major adverse cardiac events
      (MACEs) occurred in 14.0% and 5.1% of the patients with positive and negative
      ErgECHO results, respectively (p<0.001) at a median follow-up of 10.5 years. Cox
      regression survival analyses revealed that male sex, age, presence of diabetes,
      total cholesterol level of >220 mg/dL, and positive ErgECHO result itself were
      independent factors associated with MACEs. CONCLUSIONS: ErgECHO can be performed
      safely by experienced physicians and its positive result may be an independent
      risk factor for long-term adverse outcomes. It may also be an alternative tool to
      invasive ergonovine-provoked coronary angiography for the diagnosis of
      vasospastic angina.

PMID- 30238709
TI  - Fibrosis Marker Soluble ST2 Predicts Atrial Fibrillation Recurrence after
      Cryoballoon Catheter Ablation of Nonvalvular Paroxysmal Atrial Fibrillation.
AB  - BACKGROUND AND OBJECTIVES: We aimed to investigate the relationship between the
      recurrence of atrial fibrillation (AF) and fibrosis marker soluble ST2 (sST2) in
      patients with nonvalvular paroxysmal AF (PAF). METHODS: We prospectively included
      100 consecutive patients with PAF diagnosis and scheduled for cryoballoon
      catheter ablation for AF (47 males, 53 females; mean age 55.1+/-10.8 years). sST2
      plasma levels were determined using the ASPECT-PLUS assay on ASPECT Reader device
      (Critical Diagnostics). The measurement range of these measurements was 12.5-250
      ng/mL. Patients had regular follow-up visits with 12-lead electrocardiogram
      (ECG), medical history, and clinical evaluation. Twenty-four hours Holter ECG
      monitoring had been recorded 12 months after ablation. RESULTS: AF recurrence was
      detected in 22 patients after 1 year. Age, smoking history, diabetes
      mellitus,hypertension frequency, angiotensin converting enzyme inhibitor
      angiotensin receptor blocker use, CHA2DS2VASc and HAS-BLED scores, serum sST2
      level, left atrium (LA) end-diastolic diameter, LA volume and LA volume index
      were related to AF recurrence. In multivariable logistic regression analysis,
      sST2 was found to be only independent parameter for predicting AF recurrence
      (odds ratio, 1.085; p=0.001). Every 10-unit increase in sST2 was found to be
      associated with 2.103-fold increase in the risk of AF recurrence. The cut-off
      value of sST2 obtained by receiver operating characteristic curve analysis was
      30.6 ng/mL for prediction of AF recurrence (sensitivity: 77.3%, specificity:
      79.5%). The area under the curve was 0.831 (p<0.001). CONCLUSIONS: sST2, which is
      associated with atrial fibrosis, can be thought to be a useful marker for
      detection of patients with high-grade fibrosis who will get less benefit from
      cryoablation.

PMID- 30238706
TI  - Catheter Ablation of Ventricular Tachycardia in Arrhythmogenic Right Ventricular
      Dysplasia/Cardiomyopathy.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is
      predominantly an inherited cardiomyopathy with typical histopathological
      characteristics of fibro-fatty infiltration mainly involving the right
      ventricular (RV) inflow tract, RV outflow tract, and RV apex in the majority of
      patients. The above pathologic evolution frequently brings patients with ARVD/C
      to medical attention owing to the manifestation of syncope, sudden cardiac death
      (SCD), ventricular arrhythmogenesis, or heart failure. To prevent future or
      recurrent SCD, an implantable cardiac defibrillator (ICD) is highly desirable in
      patients with ARVD/C who had experienced unexplained syncope, hemodynamically
      intolerable ventricular tachycardia (VT), ventricular fibrillation, and/or
      aborted SCD. Notably, the management of frequent ventricular tachyarrhythmias in
      ARVD/C is challenging, and the use of antiarrhythmic drugs could be
      unsatisfactory or limited by the unfavorable side effects. Therefore,
      radiofrequency catheter ablation (RFCA) has been implemented to treat the drug
      refractory VT in ARVD/C for decades. However, the initial understanding of the
      link between fibro-fatty pathogenesis and ventricular arrhythmogenesis in ARVD/C
      is scarce, the efficacy and prognosis of endocardial RFCA alone were limited and
      disappointing. The electrophysiologists had broken through this frontier after
      better illustration of epicardial substrates and broadly application of
      epicardial approaches in ARVD/C. In recent works of literature, the application
      of epicardial ablation also successfully results in higher procedural success and
      decreases VT recurrences in patients with ARVD/C who are refractory to the
      endocardial approach during long-term follow-up. In this article, we review the
      important evolution on the delineation of arrhythmogenic substrates, ablation
      strategies, and ablation outcome of VT in patients with ARVD/C.

PMID- 30238710
TI  - Soluble ST2 in Paroxysmal Atrial Fibrillation: a New Biomarker that Predicts
      Recurrence?

PMID- 30238712
TI  - A New Era of Targeting Pathogenic Immune Mechanisms in Cardiovascular Disease.

PMID- 30238713
TI  - Cardiac Sarcoidosis Presenting as Complete Atrioventricular Block: Findings on
      PET/MRI.

PMID- 30238711
TI  - Treatment with 3-Bromo-4,5-Dihydroxybenzaldehyde Improves Cardiac Function by
      Inhibiting Macrophage Infiltration in Mice.
AB  - BACKGROUND AND OBJECTIVES: Appropriate inflammatory response is necessary for
      cardiac repairing after acute myocardial infarction (MI). Three-Bromo-4,5
      dihydroxybenzaldehyde (BDB) is a potent antioxidant and natural bromophenol
      compound derived from red algae. Although BDB has been shown to have an anti
      inflammatory effect, it remains unclear whether BDB affects cardiac remolding
      after MI. The aim of this study was to investigate the potential role of BDB on
      cardiac function recovery after MI in mice. METHODS: Mice were intraperitoneally
      injected with BDB (100 mg/kg) or vehicle control respectively 1 hour before MI
      and then treated every other day. Cardiac function was monitored by transthoracic
      echocardiography at day 7 after MI. The survival of mice was observed for 2 weeks
      and hematoxylin and eosin (H&E) staining was used to determine the infarct size.
      Macrophages infiltration was examined by immunofluorescence staining. Enzyme
      linked immunosorbent assay (ELISA) was used to test the production of cytokines
      associated with macrophages. The phosphorylation status of nuclear factor (NF)
      kappaB was determined by western blot. RESULTS: BDB administration dramatically
      improved cardiac function recovery, and decreased mortality and infarcted size
      after MI. Treatment with BDB reduced CD68+ macrophages, M1 and M2 macrophages
      infiltration post-MI, and suppressed the secretion of pro-inflammatory cytokines,
      such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, monocyte
      chemoattractant protein (MCP)-1, and IL-6 in the injured hearts. Furthermore, BDB
      inhibited the phosphorylation of NF-kappaB in the infarcted hearts. CONCLUSIONS:
      These data demonstrate, for the first time, that BDB treatment facilitated
      cardiac healing by suppressing pro-inflammatory cytokine secretion, and indicate
      that BDB may serve as a therapeutic agent for acute MI.

PMID- 30238714
TI  - Successful Direct Iliac Transcatheter Aortic Valve Implantation to Overcome
      Significant Tortuosity of the Thoracic Aorta.

PMID- 30238715
TI  - The Prevalence and Risk Factors of Latent Tuberculosis Infection among Health
      Care Workers Working in a Tertiary Hospital in South Korea.
AB  - BACKGROUND: The risk of tuberculosis (TB) infection among health care workers
      (HCWs) is higher than as noted among workers in the general population. The
      prevalence and risk factors of TB infection among HCWs were assessed in a
      tertiary hospital in South Korea, resulting in a conclusion of an intermediate TB
      burden within the country. METHODS: This cross-sectional study enrolled HCWs who
      underwent a QuantiFERON-TB Gold In-Tube (QFT-GIT) test to detect the presence of
      a latent TB infection (LTBI), in patients admitted to a tertiary hospital in
      South Korea in 2017. The departments of the hospital were divided into TB-related
      and TB-unrelated departments, which were based on the risk of exposure to TB
      patients. In this sense, the risk factors for LTBI, including current working in
      the TB-related departments, were analyzed. RESULTS: In this case, a total of 499
      HCWs (54 doctors, 365 nurses and 80 paramedical personnel) were enrolled in this
      study. The median age of the subjects was 31 years (range, 20-67 years), 428
      (85.8%) were female, and 208 (41.7%) were working in the TB-related departments.
      The prevalence of LTBI was 15.8% based on the QFT-GIT. Additionally, the
      prevalence of experience of exposure to pre-treatment TB patents was higher among
      HCWs working in the TB-related departments, than among HCWs working in the TB
      unrelated departments (78.8% vs. 61.9%, p<0.001). However, there was no
      significant difference in the prevalence of LTBI between the two groups (17.3%
      vs. 14.8%, p=0.458). On a review of the multivariate analysis, only the factor of
      age was independently associated with an increased risk of LTBI (p=0.006).
      CONCLUSION: Broadly speaking, the factor of age was associated with an increased
      risk of LTBI among the HCWs in South Korea. However, those workers current
      working in the TB-related departments was not associated with an increased risk
      of LTBI.

PMID- 30238716
TI  - Old Friends, Old Wine, and Old COPD Classification Are Best.

PMID- 30238717
TI  - Corrigendum: Elucidation of Bacterial Pneumonia-Causing Pathogens in Patients
      with Respiratory Viral Infection.
AB  - This corrects the article on p. 358 in vol. 80, PMID: 28905531.

PMID- 30238718
TI  - Corrigendum: Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse
      Model.
AB  - This corrects the article on p. 80 in vol. 81, PMID: 29332324.

PMID- 30238719
TI  - Corrigendum: An Increased Proportion of Apoptosis in CD4+ T Lymphocytes Isolated
      from the Peripheral Blood in Patients with Stable Chronic Obstructive Pulmonary
      Disease.
AB  - This corrects the article on p. 132 in vol. 81, PMID: 29372631.

PMID- 30238720
TI  - [The role of glial scar on axonal regeneration after spinal cord injury].
AB  - The 'glial scar' has been widely studied in the regeneration of spinal cord
      injury (SCI). For decades, mainstream scientific concept considers glial scar as
      a 'physical barrier' to impede axonal regeneration after SCI. Moreover, some
      extracellular molecules produced by glial scar are also regarded as axonal growth
      inhibitors. With the development of technology and the progress of research,
      multiple lines of new evidence challenge the pre-existing traditional notions in
      SCI repair, including the role of glial scar. This review briefly reviewed the
      history, advance, and controversy of glial scar research in SCI repair since
      1930s, hoping to recognize the roles of glial scar and crack the international
      problem of SCI regeneration.

PMID- 30238721
TI  - [Research progress of vascularized lymph node transfer for extremity lymphedema].
AB  - Objective: To review the current progress of clinical and experimental research
      of vascularized lymph node transfer for lymphedema. Methods: The domestic and
      abroad literature about vascularized lymph node transfer in treatment of
      lymphedema was reviewed and analyzed. Results: Experimental studies in animal
      model indicate that vascularized lymph node transfer can improve lymph node
      survival and show a promising effectiveness in reducing lymphedema. "Lymphatic
      wick" and "lymph pump" were the two main hypotheses proposed to explain the
      potential functional mechanism of vascularized lymph node transfer in treatment
      of lymphedema. Improvement in lymphedema symptoms are reported in most of the
      clinical trials, but the level of evidence to advocate this procedure in the
      treatment of lymphedema remains low because of the small number of the cases and
      problems in their methodologies. Conclusion: Based on current evidence,
      vascularized lymph node transfer seems to be a promising treatment for
      lymphedema, but long-term well-designed studies are required to further explore
      the effectiveness of this procedure.

PMID- 30238722
TI  - [Effectiveness analysis of maintaining the stability between the fourth and the
      fifth metacarple base during the treatment in the hamate-metacarpal joint
      injury].
AB  - Objective: To explore the effectiveness of maintaining the stability between the
      fourth and the fifth metacarple base during the treatment in the hamate
      metacarpal joint injury. Methods: Between September 2015 and June 2017, 13 cases
      of hamate-metacarpal joint injury were treated, including 12 males and 1 female,
      aged from 17 to 55 years (mean, 30.8 years). The injury causes included heavy
      boxing in 10 cases and falling in 3 cases. There were 2 cases of simple fourth
      metacarpal basal fracture, 1 basal fracture of the fourth metacarpal bone
      combined with intermetacarpal ligament fracture, 7 fractures of the fourth and
      fifth metacarpal base, 2 fourth metacarpal basal fractures combined with the
      fifth metacarpal basal fracture dislocation, and 1 base fracture of fourth and
      fifth metacarpal bone combined with hamate bone fracture. The time from injury to
      operation was 5-11 days (mean, 7.2 days). According to different damage degree
      and stability change between the fourth and the fifth metacarple base, a
      preliminary classification was made for different degrees of injury: 2 cases of
      type I, 1 case of type II, 7 cases of type III, 2 cases of type IV, and 1 case of
      type V. The patients were treated with corresponding internal fixation methods
      under the principle of stability recovery between the fourth and fifth metacarple
      base. Results: All the incisions healed by first intention without infection or
      skin necrosis. All the 13 patients were followed up 6-18 months with an average
      of 9.4 months. All fractures healed clinically, and the healing time was 5.5-8.0
      weeks with an average of 6.3 weeks. No complication such as plate breakage,
      fracture dislocation, fracture malunion, and bone nonunion occurred. Hand
      function was evaluated according to the total active motion (TAM) functional
      evaluation standard of hand surgery at 6 months after operation, and the results
      was excellent in 9 cases, good in 3 cases, and fair in 1 case, with an excellent
      and good rate of 92.3%. Conclusion: Stability between the fourth and fifth
      metacarple base is of great significance to the classification and the treatment
      of the hamate-metacarpal joint injury.

PMID- 30238723
TI  - [Ultrasound-guided percutaneous Herbert screw for the treatment of fresh
      nondisplaced carpal scaphoid fracture].
AB  - Objective: To explore the effectiveness of ultrasound-guided percutaneous Herbert
      screw for the treatment of fresh nondisplaced carpal scaphoid fracture. Methods:
      Between May 2013 and August 2015, 15 patients with fresh nondisplaced carpal
      scaphoid fractures (Krimmer type A2) were treated with ultrasound-guided Herbert
      screw fixation. There were 12 males and 3 females with an average age of 33.4
      years (range, 18-51 years). The causes of injury included 9 cases of falls, 3
      cases of training injuries, and 3 cases of machine injuries. The interval from
      injury to surgery was 2-15 days (mean, 5 days). No other complication was found.
      The operation time, intraoperative blood loss, intraoperative fluoroscopy times,
      and the fracture healing time were recorded. The wrist function was assessed by
      the modified Mayo wrist score standard. Results: The operation time was 28-53
      minutes (mean, 33.9 minutes); the intraoperative blood loss was 5-30 mL (mean,
      10.5 mL); the intraoperative fluoroscopy was 2-6 times (mean, 2.6 times). All 15
      patients were followed up 6-18 months (mean, 10.5 months). One patient developed
      pain and soreness in the skin of the nail entrance, and gradually relieved after
      fumigation. No complication such as infection occurred. All fractures healed
      clinically, and the healing time was 8-16 weeks (mean, 11.6 weeks). At last
      follow-up, the modified Mayo wrist score was 76-99 (mean, 92.5). Among them, 12
      cases were excellent, 2 cases were good, and 1 case was fair, and the excellent
      and good rate was 93.3%. Conclusion: Ultrasound-guided fixation with Herbert
      screw is a reliable treatment method for fresh nondisplaced carpal scaphoid
      fractures with small invasion, less bleeding, and small radiation damage.

PMID- 30238724
TI  - [Combined ulnar shortening osteotomy and elastic suspended fixation in treatment
      of ulnar impaction syndrome].
AB  - Objective: To investigate the effectiveness of ulnar shortening osteotomy
      combined with elastic suspension fixation for ulnar impaction syndrome caused by
      relatively long ulna. Methods: Between October 2015 and August 2016, 3 cases of
      ulnar impaction syndrome were treated. One patient was male and 2 patients were
      females. The age was 32, 29, and 59 years, respectively. One patient was
      dislocation and impaction of distal radioulnar joint for more than 1 year after
      internal fixation due to ulnar and radial open fractures. Other patients had no
      trauma and surgery, but long-term manual history. The visual analogue scale (VAS)
      scores were 7, 5, and 5, respectively. Cooney wrist function scores were rated as
      poor. Preoperative X-ray measurements of the ulnar variance was 12.7, 9.0, and
      8.7 mm, respectively. The ulna was transversely osteotomy and fixed with plate
      and screws. The distal radioulnar joint was elastic suspension fixed with mini
      plate. Results: Postoperative X-ray film showed that the matching of the distal
      radioulnar joint had no significant difference compared with the contralateral
      side. All the incisions healed by first intention without complication such as
      neurovascular injury, infection, and dislocation of the distal radioulnar joint.
      The patients were followed up 27, 17, and 23 months, respectively. At last follow
      up, X-ray film showed that all osteotomy segments achieved bony union without
      internal fixation failure. The VAS scores were 2, 0, and 1, respectively, and the
      Cooney wrist function scores were rated as excellent. Conclusion: The ulnar
      shortening osteotomy combined with elastic suspension fixation can correct the
      ulna variation, avoid the instability of the distal radioulnar joint caused by
      the extensive dissection of the tissue around the ulnar, and avoid stiffness of
      the joints caused by rigid fixation. It is an ideal treatment for ulna impaction
      syndrome.

PMID- 30238725
TI  - [Effectiveness of open wedge high tibial osteotomy on medial unicompartmental
      knee osteoarthritis].
AB  - Objective: To evaluate the effectiveness of open wedge high tibial osteotomy
      (OWHTO) in treatment of medial unicompartmental knee osteoarthritis (MUKOA).
      Methods: A clinical data of 61 cases with MUKOA who were treated with OWHTO
      between January 2015 and January 2017 were retrospectively analyzed. There are 14
      males and 47 females with an average age of 52.8 years (mean, 44-60 years). The
      body mass index ranged from 19.1 to 34.7 kg/m 2 (mean, 25.3 kg/m 2). Twenty-seven
      cases were left side and 34 cases were right side. The disease duration was 1-9
      years (mean, 5.3 years). The MUKOA was rated as stage II in 33 cases and stage
      III in 28 cases. Preoperative Hospital for Special Surgery (HSS) score was 56.0+/
      3.7. Walking visual analogue scale (VAS) score was 4.6+/-1.0. Results: The
      operation time was 49-85 minutes (mean, 66.5 minutes). The length of incision was
      10-13 cm (mean, 11.0 cm). The total overt blood loss was 80-210 mL (mean, 139.1
      mL). The postoperative bed-rest time was 1-10 days (mean, 4.7 days). All patients
      were followed up 12-24 months (mean, 17.3 months). The bearing area of tibial
      platform at 3 months after operation was 60.3%-66.8%, with an average of 63.4%.
      At 3 and 6 months after operation, the HSS score was 79.1+/-4.2 and 85.3+/-3.1
      respectively, and the VAS score was 1.7+/-0.7 and 0.6+/-0.5 respectively, all
      showing significant differences ( P<0.05). Conclusion: OWHTO is an ideal choice
      for treating MUKOA with less postoperative complications. The force line could be
      corrected by OWHTO. However, the preoperative preparations are very important,
      especially that the open angle should be measured accurately.

PMID- 30238726
TI  - [Risk factors associated with interleukin 6 level in serum after total knee
      arthroplasty].
AB  - Objective: To explore the risk factors associated with interleukin 6 (IL-6) level
      in serum after total knee arthroplasty (TKA). Methods: A retrospective study was
      made on the clinical data of 273 patients underwent primary unilateral TKA
      between July 2015 and April 2017. There were 50 males and 223 females with an
      average age of 66.3 years (range, 36-89 years), and the body mass index (BMI) was
      (25.5+/-3.7) kg/m 2. Of them, 256 patients suffered with osteoarthritis, and the
      other 17 patients with rheumatoid arthritis. Univariate analysis was made to find
      the related factors between IL-6 level in serum at 1 day after operation and
      preoperative data including gender, age, BMI, diagnosis, comorbidities,
      preoperative American Society of Anesthesiologists (ASA) grade, preoperative
      varus or valgus deformity, range of motion of the knee, preoperative level of C
      reactive protein (CRP) and IL-6 in serum, operation time, intraoperative blood
      loss, usage of drainage tube and catheter, and dosage of tranexamic acid and
      dexamethasone used on day of operation. Furthermore, the multiple linear
      regression analysis was performed to identify the risk factors. Results: The
      operation time was (79.7+/-15.6) minutes, and the intraoperative blood loss was
      (107.8+/-25.3) mL. Drainage tubes were used in 111 patients and catheters were
      used in 41 patients after operation. The dosage of tranexamic acid and
      dexamethasone used on day of operation were (3.2+/-0.8) g and (15.1+/-6.6) mg,
      respectively. The levels of IL-6 in serum were (4.48+/-3.05), (42.65+/-37.09),
      and (28.21+/-26.44) pg/mL before operation and at 1 and 3 days after operation,
      respectively. Univariate analysis showed that the level of IL-6 in serum at 1 day
      after operation was significantly higher in variables as follows: age, diagnosis,
      history of lung infection, range of motion, preoperative levels of CRP and IL-6
      in serum, intravenous dosage of tranexamic acid and dexamethasone on day of
      operation ( P<0.05). Multiple linear regression analysis showed that range of
      motion less than 90 degrees , intravenous dosage of tranexamic acid on day of
      operation less than 3 g, and dosage of dexamethasone on day of operation less
      than 10 mg were significant risk factors ( P<0.05). Conclusion: Range of motion
      less than 90 degrees , intravenous dosage of tranexamic acid on day of operation
      less than 3 g, and dosage of dexamethasone on day of operation less than 10 mg
      were independent risk factors that resulted in increased level of IL-6 in serum
      at 1 day after TKA.

PMID- 30238727
TI  - [Effect of adductor canal block combined with local infiltration anesthesia on
      rehabilitation of primary total knee arthroplasty].
AB  - Objective: To investigate the effect of adductor canal block combined with local
      infiltration anesthesia on the rehabilitation of primary total knee arthroplasty
      (TKA). Methods: A total of 104 patients who met the selection criteria for the
      first unilateral TKA between March 2017 and August 2017 were included in the
      study. They were randomly divided into trial group (53 cases) and control group
      (51 cases). In the trial group, the adductor canal block with intraoperative
      local infiltration anesthesia were performed. In the control group, only
      intraoperative local infil-tration anesthesia was performed. There was no
      significant difference in gender, age, body mass index, diagnosis, effected side,
      and the preoperative American Society of Anesthesiologists (ASA) grading between
      2 groups ( P>0.05). The operation time, length of stay, and complications were
      compared between 2 groups, as well as visual analogue scale (VAS) score of
      incision at rest and during activity, the range of motion (ROM) of knee flexion
      and extension activity, limb swelling (thigh circumference), walking distance,
      and pain VAS score while walking. Results: The operation time of the trial group
      was significantly shorter than that of the control group ( t=-2.861, P=0.005).
      However, there was no significant difference in length of stay between 2 groups (
      t=-0.975, P=0.332). The wound effusion occurred in 1 patient of trial group and 2
      of control group; hematoma occurred in 2 patients of trial group and 3 of control
      group; no symptom of intermuscular venous thrombosis occurred in 1 patient in
      each of 2 groups; ecchymosis occurred in 14 patients of trial group and 15 of
      control group; there was no significant difference in the incidence of related
      complications between 2 groups ( P>0.05). There was no significant difference in
      the preoperative VAS score at rest and during activity, ROM of knee flexion and
      extension activity, and thigh circumference between 2 groups ( P>0.05). However,
      there were significant differences in the VAS score at rest and during activity
      after 2, 4, 8, and 12 hours, ROM of knee flexion and extension activity after 1
      and 2 days, and the walking distance on the day of discharge, pain VAS scores
      while walking after 1 and 2 days and on the day of discharge, and thigh
      circumference after 1 day between 2 groups ( P<0.05). Conclusion: For the primary
      TKA, the adductor canal block combined with local infiltration anesthesia can
      early relieve the initial pain of the incision, shorten the operation time, and
      promote the mobility and functional recovery of the knee joint.

PMID- 30238728
TI  - [The assessment of the application of Taylor spatial frame in treatment of
      intermediate or distal tibiofibula fractures].
AB  - Objective: To determine the effectiveness and the safety of the Taylor spatial
      frame in treatment of intermediate or distal tibiofibula fractures. Methods: The
      clinical data of 74 patients with intermediate or distal tibiofibular fractures
      treated between January 2015 and January 2017 were retrospectively analyzed.
      According to fixation methods, they were divided into internal fixation group (26
      cases) and external fixation group (48 cases). There was no significant
      difference in the age, gender, cause of injury, type of fracture, time from
      injury to operation between 2 groups ( P>0.05). The intraoperative blood loss,
      fracture healing time, fixator removal time, and complications were recorded and
      compared. The final function evaluation criteria of Johner-Wruhs humeral shaft
      fracture were used to evaluate the function of the affected limb. The lower limb
      force line recovery after operation was evaluated according to the standard
      evaluation of LUO Congfeng et al. Results: Both groups were followed up 6-22
      months (median, 14 months). All patients obtained the fracture healing. The
      intraoperative blood loss, fracture healing time, and fixator removal time were
      significantly higher in the internal fixation group than those in the external
      fixation group ( P<0.05). There were 1 case of plate exposure, 1 case of delayed
      fracture healing, and 1 case of plate fracture in the internal fixation group;
      and there were 2 cases of delayed fracture healing and 4 cases of soft tissue
      defect in the external fixation group; no significant difference was found in the
      incidence of complications between 2 groups ( chi2=0.015, P=0.904). The function
      of the affected limb was evaluated by Johner-Wruhs standard at 10 months after
      operation, the results was excellent in 19 cases, good in 5 cases, and fair in 2
      cases in the internal fixation group, with an excellent and good rate of 92.3%;
      the results was excellent in 42 cases, good in 3 cases, and fair in 2 cases in
      the external fixation group, with an excellent and good rate of 95.7%; showing no
      significant difference between 2 groups ( chi2=0.392, P=0.531). The lower limb
      force line recovery after operation was evaluated according to the standard
      evaluation of LUO Congfeng et al.at 4 months after operation, the results was
      excellent in 24 cases, fair in 1 case, poor in 1 case in the internal fixation
      group, with an excellent and good rate of 92.3%; the results was excellent in 46
      cases, fair in 1 case, poor in 1 case in the external fixation group, with an
      excellent and good rate of 95.8%; showing no significant difference between 2
      groups ( chi2=0.520, P=0.471). Conclusion: The use of Taylor spatial frame in the
      treatment of the intermediate or distal tibiofibular fractures can obviously
      reduce the healing time and complications than the internal fixation of the
      plate. It can reduce the fracture treatment cycle and is beneficial to the
      fracture healing and limb function recovery, which is relatively safe and
      reliable.

PMID- 30238729
TI  - [Precise orthormorphia of tibial angulation deformity and shortening deformity by
      using digital technology combined with circular external fixator].
AB  - Objective: To evaluate the effectiveness of precise orthormorphia of tibial
      angulation deformity and shortening deformity by using digital technology
      combined with external fixator. Methods: Twenty-six cases of tibial angulation
      deformity combined with shortening deformity were treated between June 2012 and
      August 2016, including 12 males and 14 females aged from 1 to 19 years with an
      average age of 16.5 years. There were 6 cases of congenital patella
      pseudoarthrosis, 1 case of fibrous dysplasia of femur and tibia, 3 cases of limb
      shortening deformity caused by infantile paralysis, 16 cases of fracture
      malunion. Limb shortening was 1.5-9.5 cm (mean, 6.2 cm) before operation. The
      deformity from three-dimensional perspective was analysed by digital technology,
      the surgical procedures of lengthening and osteotomy was simulated, the
      navigation templates were completed with computer aided design (CAD) and three
      dimensional printing, and the external fixator was used to assist the lengthening
      of the tibia. X-ray films were regularly reviewed after operation to observe the
      new bone remolding, limb lengthening, load bearing line of lower limb, and
      recurrences of angulation. Results: All the patients were followed up 14-48
      months (mean, 18.8 months). There was only 1 case of superficial pin site
      infection which was cured with oral antibiotics and pin site care with mild
      disinfectants, and no complication such as bone nonunion, equines deformity, or
      vascular nerve injury occurred. The deformity of tibia and load bearing line of
      lower limb had been completely recovered according to postoperative X-ray films
      at 1 week. All the cases achieved perfect limb length as with preoperative
      design. The bone mineralization time was 12-20 weeks (mean, 11.6 weeks), the
      external fixator removal time was 18-26 weeks (mean, 14.9 weeks), and the healing
      index was 21-78 d/cm (mean, 63.4 d/cm). The postoperative flexion range of the
      injured limb was 15 degrees  less than the unaffected extremity in 1 case, and
      the situation was improved significantly after some physical manipulation and
      exercise, who completed the limb lengthening and achieved the expected
      effectiveness finally. Conclusion: Precise orthormorphia of tibial deformity by
      using digital technology, and limb lengthening with the aid of external fixator
      can achieve good effectiveness with good reliability, invasiveness, and
      precision.

PMID- 30238731
TI  - [Perioperative treatment progress of Parkinson's disease with hip fracture].
AB  - Objective: To review the progress of perioperative treatments for patients of
      Parkinson's disease and hip fractures. Methods: The related literature of
      treatments for patients of Parkinson's disease and hip fractures were reviewed
      and analyzed from the aspects such as the perioperative management, selection of
      operation ways, and prognosis. Results: The patients of Parkinson's disease are
      more likely to sustain hip fractures because of postural instability and
      osteoporosis. The perioperative treatments for patients of Parkinson's disease
      and hip fractures should be determined by orthopedists, neurologist,
      anesthesiologist, and physical therapist. There is still controversy about the
      selection of operation and surgical approach. And the prognosis of patients of
      Parkinson's disease and hip fractures are associated with the severity of
      Parkinson's disease. Conclusion: There are few clinical studies about the
      patients of Parkinson's disease and hip fractures. The mid-term and long-term
      functional outcomes of patients of Parkinson's disease and hip fractures are
      unsufficient. And the best treatments of patients of Parkinson's disease and hip
      fractures need to be further explored.

PMID- 30238730
TI  - [Preliminary study on surgical treatment of Erdheim-Chester disease].
AB  - Objective: To summarize the preliminary effectiveness of surgical treatment of
      Erdheim-Chester disease (ECD), so as to improve the understanding of the disease
      by orthopedic surgeons. Methods: The clinical data of 9 patients with ECD between
      December 2012 and October 2017 were retrospectively analysed. There were 6 males
      and 3 females with an median age of 42 years (range, 8-61 years). The disease
      duration was 4-59 months (mean, 39 months). There were 2 cases of multiple
      lesions, including 1 case involving soft tissue of the buttocks and bilateral
      tibia, 1 case involving the sinus, skull base, and proximal right tibia; 7 cases
      with single lesion, including 3 cases of right femoral neck, 1 case of proximal
      right tibia, 1 case of right humerus, and 2 cases of ribs. Nine patients were
      diagnosed according to clinical manifestations, imaging examination, and
      pathological diagnosis. Four patients underwent needle biopsy before operation
      and 5 patients were diagnosed by postoperative pathology examination. Five cases
      underwent lesional scraping and internal fixation, 1 case underwent bone scraping
      and bone grafting, and 3 cases underwent lesion resection. One of the multiple
      lesions was treated with interferon and hormone. Results: Nine patients underwent
      the surgery safely. There was no fever, wound exudation, infection, etc., and the
      incisions healed by first intention. All the patients were followed up 4-59
      months with an average of 31.4 months. One patient with bilateral tibia and hip
      soft tissue involvement continued to receive medical treatment, and the tumor was
      controlled without significant increasing. The remaining 8 patients were examined
      for X-ray films at 3, 6, and 12 months after surgery, the bone has been fused and
      the steel plate and intramedullary nail were firmly fixed, and no tumor
      recurrence was observed. At 1 year after surgery, the pain symptoms of the
      patients improved and returned to normal life; 3 of them who involving the right
      femoral neck walked freely, and the quality of life improved significantly.
      Conclusion: ECD patients can achieve the purpose of eliminating lesions and
      relieving pain after surgical treatment, and the surgical treatment has the
      advantages of quick relief of pain, improved quality of life, small side effects,
      and low economic cost when compared with medical treatment.

PMID- 30238732
TI  - [Research status of the enhanced recovery after surgery in the geriatric hip
      fractures].
AB  - Objective: To summarize the latest developments in the enhanced recovery after
      surgery (ERAS) in the geriatric hip fractures and its perioperative therapy
      management. Methods: The recent original literature on the ERAS in the geriatric
      hip fractures were extensively reviewed, illustrating the concepts and properties
      of the ERAS in the geriatric hip fractures. Results: It has been considered to be
      associated with the decreased postoperative morbidity, reduced hospital length of
      stay, and cost savings to implement ERAS protocols, including multimodal
      analgesia, inflammation control, intravenous fluid therapy, early mobilization,
      psychological counseling, and so on, in the perioperative (emergency,
      preoperative, intraoperative, postoperative) management of the geriatric hip
      fractures. The application of ERAS in the geriatric hip fractures guarantees the
      health benefits of patients and saves medical expenses, which also provides basis
      and guidance for the further development and improvement of the entire process
      perioperative management in the geriatric hip fractures. Conclusion: Significant
      progress has been made in the application of ERAS in the geriatric hip fractures.
      ERAS protocols should be a priority for perioperative therapy management in the
      geriatric hip fractures.

PMID- 30238733
TI  - [Influencing factors of medial patellofemoral ligament reconstruction for
      patellar dislocation].
AB  - Objective: To review the influencing factors of medial patellofemoral ligament
      (MPFL) reconstruction for patellar dislocation. Methods: The literature of MPFL
      reconstruction for patellar dislocation at home and abroad in recent years were
      summarized and analyzed. Results: The influencing factors such as the location of
      the femoral insertion point, the tension and the fixed angle of the grafts, the
      dysplasia of the femoral trochlear before operation, the abnormal tuberositas
      tibiae-trochlear groove value, the high position of the patellar, and the tilting
      angle of the patellar, are all the factors affecting the effectiveness of MPLF
      reconstruction. Conclusion: During MPFL reconstruction, the surgical techniques
      and elimination of other factors that caused patellar instability need to be
      focused in order to reduce the complications and operation failure.

PMID- 30238734
TI  - [Clinical application of Flow-through chimeric anterolateral thigh perforator
      flap].
AB  - Objective: To investigate the feasibility and efficacy of the Flow-through
      chimeric anterolateral thigh perforator (ALTP) flap for one-stage repair and
      revascularization in complex defects of the extremities. Methods: Between May
      2014 and June 2017, 6 patients with soft tissue defects on the limbs combined
      with dead space, bone defects, or tendon and joint exposure, were reconstructed
      with the Flow-through chimeric ALTP flap. All 6 patients were male. The patients'
      mean age was 44 years (range, 26-60 years). The mechanisms of injury were traffic
      accidents in 4 cases, wringer injury in 1 case, and bruise injury caused by heavy
      object in 1 case. The defects located at the lower extremity in 5 cases and at
      the upper extremity in 1 case. The area of the wound ranged from 7 cm*4 cm to 26
      cm*10 cm. There were 3 cases of bone defect, 3 cases of joint and tendon
      exposure, 2 cases of chronic osteomyelitis, and 2 cases of main artery injury.
      The muscle flap was inserted into the deep dead space, with perforator flap for
      superficial defect. The area of perforator flap ranged from 10 cm*5 cm to 28
      cm*11 cm and the area of muscle flap ranged from 5 cm*2 cm to 20 cm*5 cm. The
      defects on the donor sites were closed directly. Results: All the flaps were
      survival without infection and vascular crisis. The wounds of recipient and donor
      sites healed at first intention. The patients were followed up 3- 24 months
      (mean, 10 months). Good color and texture of flaps was achieved. The
      reconstructed main artery patency was achieved and the end of the affected limb
      was well transported. Only linear scar left on the donor site on thigh with no
      malfunction. Conclusion: The Flow-through chimeric ALTP flap can construct three
      dimensional soft tissue defects without sacrificing the recipient vessels. The
      Flow-through chimeric ALTP flap is an reliable and ideal method for
      reconstruction of complex wounds in the limbs with dead space and with or without
      recipient major vessels injury.

PMID- 30238735
TI  - [Effectiveness of autologous costal cartilage transplantation in repair of
      Binder's syndrome].
AB  - Objective: To investigate the technical points and effectiveness of autogenous
      costal cartilage transplantation in repair of Binder's syndrome. Methods: Between
      June 2012 and June 2017, 8 cases of Binder's syndrome were admitted. There were 3
      males and 5 females, aged 16-31 years (mean, 22 years). All patients were
      conformed to the typical manifestations of Binder's syndrome. The autogenous
      costal cartilage was harvested and carved into the nasal dorsum graft, nasal
      column graft, and nasal basement graft. Before and after operation, standard
      pictures of the anterior view, lateral view, and base view were taken to measure
      facial related parameters of nasal dorsum length, nasal columella-lobule ratio,
      nasofrontal angle, nasal columella-upper lip angle, nasal tip projection rate,
      and nasion projection. Then the effectiveness of this surgical procedure for
      Binder's syndrome was evaluated. Results: All incisions healed by first intention
      without acute infections. All patients were followed up 6-36 months, with an
      average of 18 months. The foreign body sensation in upper lip and scar
      hyperplasia in thoracic incision occurred in 1 case, respectively. The nasal
      morphology improved significantly and the coordinated relationships of the nose
      with the upper lip and face were restored postoperatively. Postoperative
      parameter measurements were taken in 6 cases. The nasal dorsum length, nasal
      columella-lobule ratio, nasofrontal angle, nasal columella-upper lip angle, nasal
      tip projection rate, and nasion projection at preoperation were significantly
      improved when compared with the values at 6 months after operation ( P<0.05). The
      difference in nasal dorsum length, nasal tip projection rate, and nasion
      projection between actual values at 6 months after operation and normal values
      was no significant ( P<0.05). There was significant difference in nasal columella
      lobule ratio between actual value at 6 months after operation and normal value (
      P>0.05). Conclusion: Autogenous costal cartilage transplantation in repair of
      Binder's syndrome can obviously improve patients' appearance of the external nose
      and middle face, and obtain the persistent effectiveness.

PMID- 30238736
TI  - [Effect of vacuum sealing drainage on expressions of transforming growth factor
      beta 1 and its receptor in diabetic foot wound].
AB  - Objective: To investigate the changes of transforming growth factor beta 1 (TGF-
      beta 1) and type II of TGF-beta-receptor (TbetaRII) expressions in wound tissue
      after the treatment of diabetic foot with vaccum sealing drainage (VSD), and to
      analyze the mechanism of accelerating wound healing. Methods: Between May 2012
      and May 2016, 80 patients with diabetic foot were randomly divided into 2 groups,
      40 cases in each group. After the same basic treatment, the wounds of VSD group
      and control group were treated with VSD and external dressing, respectively.
      There was no significant difference in gender, age, disease duration, body mass,
      foot ulcer area, and Wagner grade between 2 groups ( P>0.05). The time of
      foundation preparation and hospitalization stay of 2 groups were recorded. The
      wound tissue was collected before treatment and at 7 days after treatment, and
      the positive indexes of TGF-beta 1 and TbetaRIIexpressions were measured by
      immunohistochemical staining. Results: Before skin grafting, the patients in VSD
      group were treated with VSD for 1 to 3 times (mean, 2 times), and the patients in
      control group were treated with dressing change for 1 to 6 times (mean, 4 times).
      The time of foundation preparation and hospitalization stay in VSD group were
      significantly shorter than those in control group ( t=-13.546, P=0.036; t=
      12.831, P=0.041). The skin grafts of both groups survived smoothly and the wound
      healed well. Before treatment, immunohistochemical staining results showed that
      the positive indexes of TGF-beta 1 and TbetaRII expressions in VSD group were
      5.3+/-2.4 and 14.0+/-2.6, while those in control group were 4.4+/-2.3 and 14.7+/
      3.1, respectively. There was no significant difference between 2 groups (
      t=1.137, P=0.263; t=1.231, P=0.409). At 7 days after treatment, the positive
      indexes of TGF-beta 1 and TbetaRII expressions in VSD group were 34.3+/-2.9 and
      41.7+/-3.7, respectively, and those in control group were 5.8+/-2.0 and 18.1+/
      2.5. There were significant differences between 2 groups ( t=-35.615, P=0.003;
      t=23.725, P=0.002). Conclusion: VSD can increase the expressions of TGF-beta 1
      and TbetaRII in diabetic ulcer tissue, promote granulation tissue growth, and
      accelerate wound healing.

PMID- 30238737
TI  - [Integrative analysis of gene expression profile and DNA methylation profile of
      long-term cultivated porcine bone marrow mesenchymal stem cells].
AB  - Objective: To integrate the result of whole genome expression data and whole
      genome promoter CpG island methylation data, to screen the epigenetic modulated
      differentially expressed genes from transformed porcine bone marrow mesenchymal
      stem cells (BMSCs) after long-term cultivation. Methods: Bone marrow from 6
      landrace pigs, 3-month-old about 50 kg weight, was aspirated from the medullary
      cavity of the proximal tibia. The BMSCs were isolated, and purified by Ficoll
      density gradient centrifugation combined with adherent culture method. The
      transfor mation of BMSCs was tested by several methods including cell morphology
      observation, karyotype analysis, clone forming in soft agarose, serum requirement
      assay, and tumor forming in mice. The Agilent Pig 4x44k Gene Expression
      Microarray was used to investigate the differentially expressed mRNA. The
      methylated genes expression profile was performed using customized pig
      methylation chip. The gene expression and DNA methylation profiles were
      integrated to find out the epigenetic modulated differentially expressed genes,
      and to complete the bioinformatic analysis. Results: BMSCs showed a change in
      appearance, from the initial spindle shape to a more flatted morphology then to
      small contact shape. After additional passages, BMSCs gradually acquired recovery
      of proliferating capacity and transformation properties such as anchorage
      independent growth, chromosomal abnormality, and tumor formation in nude mice.
      The gene chip analysis demonstrated that 257 genes were upregulated and 315 genes
      were downregulated during long-term cultures as well as multiple signal pathways
      transduction involved, such as cell cycle, ECM-receptor interaction, focal
      adhesion, regulation of actin cytoskeleton, pathways in cancer, and P53. The
      analysis from methylation chip of coding genes suggested epigenetic regulation
      was involved in BMSCs spontaneous transformation and play a important role on it;
      962 genes were hypermethylated and 1219 genes were hypomethylated, which were
      involved in the biological process of cellular metabolic, structure, and tumor
      generation. The combined analysis of genes regulated by methylation in the
      transformation process of BMSCs found that the methylation changes of the 35
      genes were contrary to the direction of expression change (correlation
      coefficient r=-0.686, P=0.000); in which the methylation level of 21 genes
      promoter regions were increased while the gene expression decreased, and the
      methylation level of the 14 genes promoter regions decreased and the gene
      expression increased. At the same time, KEGG enrichment analysis revealed
      multiple genes regulated by methylation, involved in stem cell differentiation
      and multiple cell signaling pathways. Among the 14 down-regulated genes, many of
      them have the role of regulating the interaction of tumor and immunization, and
      the change of the methylation status of the CDKN3 promoter region may be closely
      related to the cell oncology. Conclusion: The results deepen our understanding of
      the crucial role of coding genes methylation modification in BMSCs
      transformation, and may provide new approach to establish safe criteria for BMSCs
      clinical applications and transformation prevention.

PMID- 30238738
TI  - [Effects of adipose-derived stem cells and endothelial cells on survival and
      neovascularization of fat tissue transplants].
AB  - Objective: To investigate the effects of adipose-derived stem cells (ADSCs) and
      endothelial cells (ECs) on the survival and neovascularization of fat tissue
      transplants. Methods: The ADSCs were isolated by collagenase digestion from the
      adipose tissues voluntarily donated by the patients undergoing mastectomy, and
      subcultured. The passage 3 ADSCs were used for subsequent experiments. The
      residual fat tissues were used to prepare fat particles (FPs). The human
      umbilical vein endothelial cells (HUVECs) were used as ECs for subsequent
      experiments. Eighty healthy male nude mice, aged 4-6 weeks, were randomly divided
      into 4 groups ( n=20). The mice were received subcutaneous injection at the
      dorsum of 1 mL FPs+0.3 mL normal saline (NS) in control group, 1 mL FPs+2*10 6
      ECs+0.3 mL NS in ECs group, 1 mL FPs+2*10 6 ADSCs+0.3 mL NS in ADSCs group, and 1
      mL FPs+1*10 6 ECs+1*10 6 ADSCs+0.3 NS in ADSCs+ECs group. General observations of
      the injection sites were performed, and the survival of the mice was recorded. At
      2, 4, 8, and 12 weeks after injection, grafted fat tissues were firstly assessed
      by ultrasonography, then they were collected for volume measurement (water
      displacement method) and histology observation (HE staining and
      immunofluorescence staining). Results: All mice survived until the end of
      experiment. At each time point, no significant difference was noted between
      groups in ultrasonography assay. There was no significant blood flow signal in
      the grafted fat tissues, or cysts, calcification, solid occupying in recipient
      area. Generally, the volume of grafted fat tissues decreased with time in all
      groups. Specifically, the volumes of grafted fat tissues were larger in ADSCs
      group and ADSCs+ECs group than that in control group and ECs group ( P<0.05) at
      each time point, and in ADSCs group than in ADSCs+ECs group ( P<0.05) at 8 and 12
      weeks. HE staining showed that all groups had similar tendencies in general
      histology changes, and remodeling in ADSCs group was the fastest than in the
      other groups. By immunofluorescence staining for neovascularization, the new
      vessels in all groups were increasing with time. The vessel densities were higher
      in ECs group, ADSCs group, and ADSCs+ECs group than in control group ( P<0.05) at
      each time point, in ADSCs group than in ECs group and ADSCs+ECs group ( P<0.05)
      at 4 weeks, in ADSCs group and ADSCs+ECs group than in ECs group ( P<0.05) at 8
      and 12 weeks. Conclusion: ADSCs can significantly increase the survival of
      transplanted fat tissue, which may be related to promoting the
      neovascularization.

PMID- 30238740
TI  - ?

PMID- 30238739
TI  - [Preparation and biocompatibility of nano polypyrrole/chitin composite membrane].
AB  - Objective: To prepare nano polypyrrole (PPy)/chitin composite membrane and
      observe their biocompatibility. Methods: The nano PPy was synthesized by
      microemulsion polymerization, blended with chitosan and then formed membranes.
      The membranes were then modified by acetylation to get the experimental membranes
      (nano PPy/chitin composite membranes, group A). The chitosan membranes (group B)
      and chitin ones (group C) modified by acetylation acted as control. Scanning
      electron microscopy and FT-IR spectra were used to identify the nano PPy and the
      membranes of each group. And the conductivity of membranes of each group was
      measured. Schwann cells were co-cultured in vitro with each group membranes to
      observe the biocompatibility by inverted microscope observing, living cell
      staining, cell counting, and immunofluorescence staining. The lysozyme solution
      was used to evaluate the degradation of the membranes in vitro. Results: The FT
      IR spectra showed that the characteristic vibrational absorption peaks of C=C
      from nano PPy appeared at 1 543.4 cm -1 and 1 458.4 cm -1. Scanning electron
      microscopy observation revealed that the size of nano PPy particles was about 100
      200 nm. The nano PPy particles were synthesized. It was successful to turn
      chitosan to chitin by the acetylation, which was investigated by FT-IR analysis
      of membranes in groups A and C. The characteristic peaks of the amide II band
      around 1 562 cm -1 appeared after acetylated modification. Conductivity test
      showed that the conductivity of membranes in group A was about (1.259 2+/-0.005
      7)*10 -3 S/cm, while the conductivity of the membranes in groups B and C was not
      detected. The nano PPy particles uniformly distributed on the surface of
      membranes in group A were observed by scanning electron microscope; the membranes
      in control groups were smooth. As a result, the nano PPy/chitin composite
      membranes with electrical conductivity were obtained. The cultured Schwann cells
      were found to survive with good function by fluorescein diacetate live cell
      staining, soluble protein-100 immunofluorescence staining, and inverted
      microscope observing. The cell counting showed that the proliferation of Schwann
      cells after 2 days and 4 days of group A was more than that of the two control
      groups, and the differences were significant ( P<0.05). It indicated that the
      nano PPy/chitin composite membranes had better ability of adhesion and
      proliferation than those of chitosan and chitin membranes. The degradation of
      membranes in vitro showed that the degradation rates of membranes in groups A and
      C were significantly higher than those in group B at all time points ( P<0.05).
      In a word, the degradation performance of the membranes modified by acetylation
      was better than that of chitosan membranes under the same condition. Conclusion:
      The nano PPy and chitosan can be blended and modified by acetylation
      successfully. Nano PPy/chitin composite membranes had electrical conductivity,
      degradability, and good biocompatibility in vitro.

PMID- 30238741
TI  - [Progress in biocompatibility and surface modification of nickel titanium shape
      memory alloys].
AB  - Objective: To summarize the research progress of biocompatibility and surface
      modification of nickel titanium shape memory alloys (Ni-Ti SMA). Methods: The
      relative researches about Ni-Ti SMA at home and abroad were reviewed, collated,
      analyzed, and summarized. Results: At present, Ni-Ti SMA as an internal fixation
      material has been widely used in clinic. It has the following advantages: the
      super elasticity, the shape memory characteristic, the good wear resistance, and
      the strong corrosion resistance. It also can effectively avoid the internal
      fixator rupture caused by stress shielding. After surface modification, the
      biocompatibility of Ni-Ti SMA has been improved. Conclusion: The Ni-Ti SMA is the
      most promising alloy material for the long-term internal fixator because of its
      excellent material properties.

PMID- 30238742
TI  - [Research progress of chronic wound debridement].
AB  - Objective: To review the research progress of chronic wound debridement. Methods:
      The recent related literature concerning the mechanisms, advantages, limitations,
      and indications of the technologies of chronic wound debridement was extensively
      consulted, reviewed, and summarized. Results: Debridement is essential for
      chronic wound healing, which includes autolytic debridement, enzymatic
      debridement, biodebridement, mechanical debridement, sharp/surgical debridement,
      ultrasound debridement, hydrosurgery debridement, and coblation debridement. Each
      technique has its own advantages and disadvantages. Conclusion: There are many
      types of technologies of chronic wound debridement, which can be chosen according
      to clinical conditions. It is showed there are more significant advantages
      associated with the technique of coblation debridement relatively, which also has
      greater potential. Further study is needed to improve its efficacy.

PMID- 30238743
TI  - Architecturally Robust Graphene-Encapsulated MXene Ti2CT x@Polyaniline Composite
      for High-Performance Pouch-Type Asymmetric Supercapacitor.
AB  - A harmonized three-component composite system which preserves the characteristics
      of individual components is of interest in the field of energy storage. Here, we
      present a graphene-encapsulated MXene Ti2CT x@polyaniline composite (GMP)
      material realized in a systematically stable configuration with different ternary
      nanomaterials for supercapacitor electrodes. Due to the different zeta-potentials
      in a high-pH solution, chemically converted graphene (negatively charged) is
      thoroughly unfolded to allow full encapsulation, but the MXene Ti2CT
      x@polyaniline composite with a low positive zeta-potential is easily attracted
      toward a counter-charged substance. The obtained GMP electrode exhibits improved
      cycling stability and better electrochemical performance owing to the use of
      mechanically robust and chemically inert graphene and the densely intercalated
      conductive polyaniline between the multilayer MXenes. The GMP electrode has a
      high gravimetric capacitance of 635 F g-1 (volumetric capacitance of 1143 F cm-3)
      at a current density of 1 A g-1 with excellent cycling stability of 97.54% after
      10 000 cycles. Furthermore, the asymmetric pouch-type supercapacitor assembled
      using the GMP as a positive electrode and graphene as a negative electrode yields
      a high energy density of 42.3 Wh kg-1 at a power density of 950 W kg-1 and
      remarkable cycling stability (94.25% after 10 000 cycles at 10 A g-1).

PMID- 30238744
TI  - Hierarchical Self-Organization of Chiral Columns from Chiral Supramolecular
      Spheres.
AB  - The supramolecular column is an archetypal architecture in the field of periodic
      liquid crystalline and crystalline arrays. Columns are generated via self
      assembly, coassembly, and polymerization of monomers containing molecules shaped
      as discs, tapered, twin- and Janus-tapered, crowns, hat-shaped crowns, and
      fragments thereof. These supramolecular columns can be helical and therefore
      exhibit chirality. In contrast, spheres represent a fundamentally distinct
      architecture, generated from conical and crown-like molecules, which self
      organize into body-centered cubic, Pm3 n cubic (also known as Frank-Kasper A15),
      and tetragonal (also known as Frank-Kasper sigma) phases. Supramolecular
      spherical aggregates are not known to further assemble into a columnar
      architecture, except as an intermediate state between a columnar periodic array
      and a cubic phase. In the present work, a chiral dendronized
      cyclotetraveratrylene (CTTV) derivative is demonstrated to self-organize into a
      supramolecular column unexpectedly constructed from supramolecular spheres, with
      no subsequent transition to a cubic phase. Structural and retrostructural
      analysis using a combination of differential scanning calorimetry, X-ray
      diffraction (XRD), molecular modeling, and simulation of XRD patterns reveals
      that this CTTV derivative, which is functionalized with eight chiral first
      generation minidendrons, self-organizes via a column-from-spheres model. The
      transition from column to column-from-spheres was monitored by circular dichroism
      spectroscopy, which demonstrated that both the supramolecular column and
      supramolecular spheres are chiral. This column-from-spheres model, which unites
      two fundamentally distinct self-assembled architectures, provides a new mechanism
      to self-organize supramolecular columnar architectures.

PMID- 30238745
TI  - Office Chromatography: Miniaturized All-in-One Open-Source System for Planar
      Chromatography.
AB  - Current high-performance-thin-layer-chromatography instrumentation is offline and
      stepwise automated. However, moderate miniaturization offers many advantages and
      together with the transfer of modern print and media technologies to the field of
      chromatography (office chromatography) it opens up new avenues. This is
      demonstrated in an all-in-one open-source system developed for planar
      chromatography and especially for ultrathin-layer chromatography. Using an
      InkShield board to control a thermal inkjet cartridge, picoliter drops were
      printed at a resolution of 96 dpi on the adsorbent layer. Using Marlin, a popular
      firmware in 3D printing, Cartesian movement of the print head was made possible
      for full control of the printing process. Open-source software was developed to
      control the device in each operation step. Sample solutions and mobile phase were
      inkjet-printed, exemplarily shown for the analysis of dye- or paraben-mixture
      solutions. Light-emitting diodes (LEDs) were investigated for documentation. For
      example, deep UV LEDs gave access to 254 nm light, and RGB LEDs gave access to
      the visible-light range. Calibration functions with correlation coefficients
      superior to 0.999 were obtained by videodensitometry. The developed modular open
      source hardware was compact (26 * 31 * 26 cm3), light (<3 kg), and affordable
      (?810). For the given analyses, the footprint of current instrumentation needed
      was miniaturized by a factor of 9. The highly reduced material design complies
      with green chemistry and lean laboratory. The design and instruction to reproduce
      the all-in-one open-source system were made freely available at
      https://github.com/OfficeChromatography . It is intended to boost progress and
      understanding by the nature of do it yourself.

PMID- 30238746
TI  - Albumin-Stabilized Metal-Organic Nanoparticles for Effective Delivery of Metal
      Complex Anticancer Drugs.
AB  - Many metal-organic complexes showed potent anticancer efficacy, but their
      clinical applications were limited by the lack of administration route because of
      their poor solubility. To make metal-organic nanoparticles (MONPs) comprising
      metal complex drugs is a new formulation strategy for their administration.
      Herein, we developed a facile synthesis of an MONP composed of bovine serum
      albumin (BSA), Cu2+, and an anticancer agent, 5-nitro-8-hydroxyquinoline (NQ)
      with albumin as a nanoreactor. The resultant BSA/Cu/NQ nanoparticle (BSA/Cu/NQ
      NP) showed good stability in different physiological buffers and could target
      tumors through the enhanced permeability and retention effect and receptor
      mediated cellular uptake. As the BSA/Cu/NQ NP could be readily and efficiently
      internalized by cancer cells, it showed much higher cytotoxic cancer cells than
      the NQ + Cu(II) complex and NQ. Therefore, the treatment with BSA/Cu/NQ NP
      noticeably enhanced the anticancer efficacy without causing systemic toxicity,
      indicating that such a facile preparation method has great potential to prepare
      other metal complex nanoparticles for drug delivery.

PMID- 30238747
TI  - Two-Dimensional Janus Transition Metal Oxides and Chalcogenides: Multifunctional
      Properties for Photocatalysts, Electronics, and Energy Conversion.
AB  - The fast development of high-performance devices for diverse applications
      requires nanoscale materials with multifunctional properties, motivating
      theoretical exploration into novel two-dimensional (2D) materials. In this work,
      we propose a new family of 2D nanomaterials, Janus transition metal oxides and
      chalcogenides MXY (M = Ti, Zr, or Hf; X = S or Se; Y = O or S; X ? Y) monolayers,
      for their versatile applications. We find that the Janus MXY monolayers are
      semiconductors with a wide range of band gaps ranging from 0.739 to 2.884 eV. We
      show that TiSO, ZrSO, and HfSO monolayers are promising candidates for
      photocatalysis because of their suitable band gaps and optimal redox potentials
      for water splitting, and ZrSeS and HfSeS monolayers are suitable candidates for
      nanoscale electronics because of their high carrier mobility. We further show
      that TiSO, ZrSO, and ZrSeO monolayers possess large piezoelectric properties
      because of the broken inversion symmetry stemmed from the different atomic sizes
      and electronegativities of the X and Y elements, which are better or comparable
      to other 2D and bulk piezoelectric materials. Our study demonstrates that the 2D
      Janus MXYs may find versatile applications into photocatalysts, electronics,
      sensors, and energy harvesting/conversion.

PMID- 30238748
TI  - Ultrasensitive Detection of Serum MicroRNA Using Branched DNA-Based SERS Platform
      Combining Simultaneous Detection of alpha-Fetoprotein for Early Diagnosis of
      Liver Cancer.
AB  - We provided an ultrasensitive sensing strategy for microRNA detection by first
      employing branched DNA. With the aid of microcontact printing, we realized the
      multiplex sensing of different kinds of liver cancer biomarkers: microRNA and
      protein simultaneously. Delicately designed branched DNA included multiple
      complementary sticky ends as probe to microRNA capture and the double-stranded
      rigid branched core to increase the active sticky-ends distance and expose more
      DNA probes for sensitivity. The branched DNA enables 2 orders of magnitude
      increase in sensitivity for microRNA detection over single-stranded DNA. The
      limit of detection reaches as low as 10 attomolar (S/N = 3) for miR-223 and 10-12
      M for alpha-fetoprotein. In addition, this system shows high selectivity and
      appropriate reproducibility (the relative standard deviation is less than 20%) in
      physiological media. Serum samples are tested and the results of alpha
      fetoprotein are in good agreement with the current gold-standard method,
      electrochemiluminescence immunoassay analyzer. The results suggest the
      reliability of this approach in physiological media and show high potential in
      the sensing of low abundant microRNA in serum, especially for early diagnosis of
      primary liver cancers.

PMID- 30238749
TI  - Dihedral Angle Control of Blue Thermally Activated Delayed Fluorescent Emitters
      through Donor Substitution Position for Efficient Reverse Intersystem Crossing.
AB  - This study shows a molecular design strategy for controlling the dihedral angle
      of two carbazole donors linked to a 2,4-diphenyl-1,3,5-triazine acceptor by a
      phenyl unit. Using this approach, six thermally activated delayed fluorescence
      emitters were synthesized with donors placed in various positions around a
      central phenyl core, and the photophysical relationship between the donor
      position and its dihedral angle was investigated. We demonstrate that this angle
      can affect both the strength of the charge transfer state and the conjugation
      across the entire molecule, effectively changing the singlet-triplet energy gap
      of the system. We conclude that materials containing two substituted -ortho
      donors or one -ortho and an adjacent -meta have the smallest energy gaps and the
      shortest delayed fluorescence lifetimes. On the other hand, emitters with no 
      ortho substituted donors have larger energy gaps and slow-to-negligible delayed
      fluorescence. When applying these materials to organic light-emitting diodes,
      these blue-emitting devices have a range of electrical properties, the best
      producing efficiencies as high as 21.8% together with high resistance to roll-off
      that correlate with the reverse intersystem crossing rates obtained.

PMID- 30238750
TI  - Stimuli-Responsive Luminescent Bis-Tridentate Ru(II) Complexes toward the Design
      of Functional Materials.
AB  - We report here the synthesis, characterization, and photophysics of two bis
      tridentate Ru(II) complexes based on a heteroditopic ligand and thoroughly
      studied their stimuli-responsive behaviors toward the design of functional
      materials. Both complexes display emission at room temperature having lifetimes
      in the range of 0.5-70.0 ns, depending on coligand and solvent. Substantial
      modulations of absorption and emission spectral behaviors of the complexes were
      done upon interaction with anions, and anion-induced changes in the properties
      lead to recognition of selected anions in both organic and aqueous media.
      Photophysical properties of the complexes were also tuned by changing the pH of
      the medium, and p Ka values in both ground and excited states were determined.
      The presence of free pyridine-imidazole motifs in the complexes leads to
      substantial modulation of the optical properties and switching of the emission
      properties upon interaction with selected cations as well as with protons. Fe2+,
      Co2+, Ni2+, and Cu2+ trigger emission quenching, while Zn2+ induces finite
      enhancement of the emission intensity in the complexes. In essence, modulation of
      the optical properties and switching of luminescence properties of the complexes
      were accomplished by a variety of the external stimuli such as anions, cations,
      protons, and pH, as well as solvent polarity. Importantly, the optical outputs in
      response to an appropriate set of stimuli were utilized to mimic the functions of
      two-input IMPLICATION, NOR, and XNOR logic gates.

PMID- 30238751
TI  - Quantum-Chemical Insights into the Phosphorescence Efficiencies of Blue-Emitting
      Platinum Complexes with Phenylene-Bridged Pincer Ligands.
AB  - Blue phosphorescent platinum complexes with phenylene-bridged pincer ligands,
      [Pt(dmib)Cl] [1; dmib = m-bis(methylimidazolyl)benzene], [Pt(mizb)Cl] [2; mizb =
      bis( N-methylimidazolium)benzene], and [Pt(dpzb)Cl] [3; dpzb = m-bis(3,5
      dimethylpyrazolyl)benzene], have been investigated theoretically to rationalize
      the marked differences of their phosphorescence efficiencies. On the basis of
      density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations, the
      geometrical and electronic structures, absorption and emission properties, and
      radiative and nonradiative processes are analyzed in detail. The emission from
      the emissive lowest triplet state (T1) originates from a mixture of metal-to
      ligand charge-transfer (3MLCT) and intraligand charge-transfer (3ILCT) states.
      The calculated radiative decay rate constants of T1 of the complexes are
      comparable and in the same order of magnitude with the experimental measurements.
      Therefore, the potential energy profiles for the deactivation processes from T1
      via temperature-independent and -dependent pathways are explored to reveal the
      effect of nonradiative decay on phosphorescence. The calculated results indicate
      that the very weak emission of 3 could be ascribed to the deactivation process
      via the metal-centered (3MC) state, which can be readily accessible via a
      spontaneous process from the T1 state. This work provides more in-depth insight
      into the nature of the emissive excited state, shielding light on a better
      understanding of the excited-state behavior of phosphorescent platinum complexes.

PMID- 30238752
TI  - Room Temperature Metal-Catalyzed Oxidative Acylation of Electron-Deficient
      Heteroarenes with Alkynes, Its Mechanism, and Application Studies.
AB  - Herein, we report an original one-step, simple, room-temperature, regioselective
      Minisci reaction for the acylation of electron-deficient heteroarenes with
      alkynes. The method has broad functional group compatibility and gives
      exclusively monoacylated products in good to excellent yields. The mechanistic
      pathway was analyzed based on a series of experiments confirming the involvement
      of a radical pathway. The 18O-labeling experiment suggested that water is a
      source of oxygen in the acylated product, and head space GC-MS experiment shows
      the C-C cleavage occurs via release as CO2.

PMID- 30238753
TI  - Intrinsic Electric Fields in Two-dimensional Materials Boost the Solar-to
      Hydrogen Efficiency for Photocatalytic Water Splitting.
AB  - Two-dimensional (2D) materials with the vertical intrinsic electric fields show
      great promise in inhibiting the recombination of photogenerated carriers and
      widening light absorption region for the photocatalytic applications. For the
      first time, we investigated the potential feasibility of the experimentally
      attainable 2D M2X3 (M = Al, Ga, In; X = S, Se, Te) family featuring out-of-plane
      ferroelectricity used in photocatalytic water splitting. By using first
      principles calculations, all the nine members of 2D M2X3 are verified to be
      available photocatalysts for overall water splitting. The predicted solar-to
      hydrogen efficiency of Al2Te3, Ga2Se3, Ga2Te3, In2S3, In2Se3, and In2Te3 are
      larger than 10%. Excitingly, In2Te3 is manifested to be an infrared-light driven
      photocatalyst, and its solar-to-hydrogen efficiency limit using the full solar
      spectrum even reaches up to 32.1%, which breaks the conventional theoretical
      efficiency limit.

PMID- 30238754
TI  - Next Steps on in Silico 2DE Analyses of Chromosome 18 Proteoforms.
AB  - In the boundaries of the chromosome-centric Human Proteome Project (c-HPP) to
      obtain information about proteoforms coded by chromosome 18, several cell lines
      (HepG2, glioblastoma, LEH), normal liver, and plasma were analyzed. In our study,
      we have been using proteoform separation by two-dimensional electrophoresis (2DE)
      (a sectional analysis) and a semivirtual 2DE with following shotgun mass
      spectrometry using LC-ESI-MS/MS. Previously, we published a first draft of this
      research, where only HepG2 cells were tested. Here, we present the next step
      using more detailed analysis and more samples. Altogether, confident (2
      significant sequences minimum) information about proteoforms of 117 isoforms
      coded by 104 genes of chromosome 18 was obtained. The 3D-graphs showing
      distribution of different proteoforms from the same gene in the 2D map were
      generated. Additionally, a semivirtual 2DE approach has allowed for detecting
      more proteoforms and estimating their pI more precisely. Data are available via
      ProteomeXchange with identifier PXD010142.

PMID- 30238755
TI  - Obstructive jaundice secondary to a hepatic hydatid cyst.
AB  - The rupture of a hepatic hydatid cyst into the intrahepatic bile ducts is one the
      most common and serious complication of hepatic hydatidosis and occurs in 5-25%
      of cases. (1, 2, 3). Endoscopic retrograde cholangiopancreatography (ERCP) plays
      an indisputable role in the diagnosis and treatment of this condition.

PMID- 30238756
TI  - Comment to the letter "Acute appendicitis after a colonic endoscopic submucosal
      resection".
AB  - We read with interest the letter to the editor "Acute appendicitis after a
      colonic endoscopic submucosal resection" by Serrano Gonzalez J et al., which was
      published in the Revista Espanola de Enfermedades Digestivas (The Spanish Journal
      of Gastroenterology) issue 3, 2018. We would like to clarify the following
      aspects mentioned in this letter.

PMID- 30238757
TI  - Laparoscopic cholecystectomy complications: a new case report of a right hepatic
      artery pseudoaneurysm that caused jaundice.
AB  - Iatrogenic vascular injuries of the hepatic artery are infrequent and a serious
      complication of LC. There is no doubt about the many advantages of LC when
      compared to open cholecystectomy. Despite this, there is an increase in the
      reported incidence (0.3%-1.0%) of biliary and vascular injuries. Most arterial
      complications are due to direct injury or diathermy shortening on surgical clips
      and HAP is one of them. We present a case of a 39-year old male patient who
      presented with this complication and how it was resolved.

PMID- 30238758
TI  - A new reported case of ileocecal infiltrative endometriosis, a disease which is
      probably underdiagnosed.
AB  - We have read the recent publications by Guerra et al. and Avila et al. of two
      clinical cases of ileocecal infiltrative endometriosis. We present a new case and
      wonder if this disease is more frequent than previously thought.

PMID- 30238759
TI  - Crohn's disease and cystic fibrosis: there is still a lot to learn.
AB  - The relationship between cystic fibrosis (CF) and the risk of developing
      inflammatory bowel disease (IBD) is not clear. CFTR mutations can influence
      dysbiosis and increased intestinal permeability, which are two key elements in
      the pathophysiology of IBD. These patients have increased intestinal
      inflammation, as demonstrated by increase pro-inflammatory gene expression in the
      bowel, specific fecal markers (fecal calprotectin), gross lesions (capsule
      endoscopy) and histological lesions on examination of surgical specimens.

PMID- 30238760
TI  - A giant abdominal collection: when things are not what they seem.
AB  - Endoscopic ultrasound-guided transluminal drainage (EUS-TD) has become the
      standard of care for the treatment of peripancreatic fluid collections (PFCs).
      New lumen-apposing metal stents (LAMS) have facilitated the drainage technique .
      However, this fact should not cloud our view when planning a EUS-TD, as
      occasionally things are not what they seem.

PMID- 30238761
TI  - The sedation issue: accumulating data while failing to advance towards a
      solution?
AB  - My reading of the monographic issue of April 2018, devoted by REED to sedation in
      digestive endoscopy, evoked in methe reflections written in this Scientific
      Lettter.

PMID- 30238762
TI  - Biliary bleeding due to a hepatic artery pseudoaneurysm rupture.
AB  - Hepatic artery pseudoaneurysm is a rare cause of upper gastrointestinal bleeding.
      Traumatic etiology is frequent (vascular anastomosis or iatrogenesisia), although
      it is also related to infectious or inflammatory diseases. We report the case of
      a 65-year-old patient, with hematemesis due to hepatic artery branch
      pseudoaneurysm rupture, in the context of infectious endocarditis. The diagnosis
      was made by angioTC, using arteriography for embolization.

PMID- 30238763
TI  - Metastasis of dermatofibrosarcoma diagnosed by capsule endoscopy.
AB  - In the study of obscure gastrointestinal bleeding, which includes iron-deficiency
      anemia, the capsule endoscopy is a valuable diagnostic tool. In the different
      series the presence of tumors reaches 16% as the cause of it. We present the case
      of a rare tumor with metastatic extension in the small intestine in which the
      capsule endoscopy was key to the diagnosis and survival of the patient.

PMID- 30238764
TI  - An unusual case report of inflammatory fibrous polyps in the upper
      gastrointestinal tract.
AB  - Inflammatory fibrous polyps (IFPs) were considered to be benign and umcommon,
      which can seriously affect the quality of life. We reported a case with the IFP
      presented with atypical symptoms and the so-called "ball valve syndrome". The
      final diagnosis is ultimately made after surgery. At 18 months of follow-up, the
      case remained symptom-free. It is worth mentioning, the definitive diagnosis of
      IFPs is always difficult to reach, which should be clinical, radiologic,
      endoscopic, histological, and immunohistochemical, although abdominal imageology,
      gastrointestinal endoscopy and endoscopic ultrasonography(EUS) may provide some
      important clues of the disease. Although therapy options usually include
      endoscopic mucosal resection and surgical excision, the preferred method was
      mainly depending on the size, location, biological property of the lesion and
      clinical presentations.

PMID- 30238765
TI  - Iatrogenic superior mesenteric artery syndrome.
AB  - We have carefully read the article "Superior mesenteric artery syndrome: an
      uncommon cause of intestinal obstruction" by Jose Barquin-Yaguez et al. and we
      would like to report one case with the same diagnosis but with another etiology.

PMID- 30238766
TI  - Meckel's diverticulitis: a laparoscopic approach.
AB  - Meckel's diverticulum is an infrequent malformation (2% of the population) and
      the most frequent complication is bleeding followed by diverticulitis. This
      usually occurs with clinical signs and symptoms of acute appendicitis in adults.
      The diagnosis requires a high index of suspicion and is based on complementary
      tests in most cases (mainly CT).

PMID- 30238767
TI  - Symptomatic exfoliative esophagitis induced by dabigatran.
AB  - Dabigatran is an oral anticoagulant prescribed as an alternative to warfarin
      which has been associated with exfoliative esophagitis and esophageal ulcer. We
      report a new case of dabigatran-induced exfoliative esophagitis where the mucosal
      injury improved after prescribing proton-pump inhibitors and ingesting medication
      with sufficient water.

PMID- 30238768
TI  - Iron-modulated virulence factors of Entamoeba histolytica.
AB  - Entamoeba histolytica is a human parasite that causes amoebiasis, a disease that
      affects the colon and liver and is prevalent worldwide. This protozoan requires a
      high concentration of iron to survive and reproduce. Iron modulates the
      expression of parasite virulence factors, including hemoglobinases, hemoglobin
      binding proteins and cysteine proteases, as well as proteins related to the
      amoebic cytoskeleton. This review summarizes the virulence factors that are
      affected by iron, resulting in upregulation or downregulation of E. histolytica
      genes. This review also discusses the functionality of iron in the mechanisms of
      pathogenesis.

PMID- 30238769
TI  - Effectiveness and safety of ertapenem used in hospital-at-home units: data from
      Spanish Outpatient Parenteral Antimicrobial Therapy Registry.
AB  - AIM: To evaluate the effectiveness and safety of ertapenem in patients
      hospitalized at home. PATIENTS & METHODS: Retrospective analysis of data from
      Spanish Outpatient Parenteral Antimicrobial Therapy (OPAT) registry. RESULTS:
      Data from 1428 patients (median age 70 years; 5.4% institutionalized) and 1547
      infectious processes (24% self-administration) were analyzed. Clinical cure or
      improvement was achieved in 93.8% of cases. Rate of related readmissions was
      4.2%, of clinically important complications -3.9%, and of adverse drug reactions 
      3.2%. High comorbidity burden, contagion in nursing home and certain types of
      infection were associated with worse prognosis. Self-administration was effective
      and safe, except in case of nursing home-acquired infections. CONCLUSION:
      Ertapenem OPAT was effective and safe. Caregivers in nursing homes should be
      better trained in OPAT-related procedures.

PMID- 30238770
TI  - Genetic and population analyses of Vibrio parahaemolyticus isolates from three
      major coastal regions in China.
AB  - AIM: This study aims to evaluate the genetic and population structure of Vibrio
      parahaemolyticus in the major coastal regions of China. MATERIALS & METHODS:
      Multilocus sequence typing was performed. RESULTS: Insertion of large sequence
      into recA happened in nearly 30 strains, which were untypeable by multilocus
      sequence typing. A collection of 307 V. parahaemolyticus isolates were typed into
      160 sequence types, including 117 novel ones. eBURST analysis revealed five
      clonal complexes, 11 doublets, and 108 singletons. The 160 sequence types formed
      two main lineages in the phylogenetic analysis. CONCLUSION: V. parahaemolyticus
      along the Chinese coastal regions exhibits high levels of genetic diversity and
      has undergone significant purifying selection and frequent recombination. A
      deeper understanding of V. parahaemolyticus genetic diversity could be obtained
      at the level of genome sequences.

PMID- 30238772
TI  - Is HOTAIR really involved in neuroendocrine prostate cancer differentiation?

PMID- 30238773
TI  - Could mycobacterial MelF protein (Rv1936) be used as a potential drug target?

PMID- 30238771
TI  - Indomethacin increases severity of Clostridium difficile infection in mouse
      model.
AB  - AIM: To evaluate the effect on the nonsteroidal anti-inflammatory drug
      indomethacin on Clostridium difficile infection (CDI) severity. MATERIALS &
      METHODS: Indomethacin was administered in two different mouse models of
      antibiotic-associated CDI in two different facilities, using a low and high dose
      of indomethacin. RESULTS: Indomethacin administration caused weight loss,
      increased the signs of severe infection and worsened histopathological damage,
      leading to 100% mortality during CDI. Indomethacin-treated, antibiotic-exposed
      mice infected with C. difficile had enhanced intestinal inflammation with
      increased expression of KC, IL-1beta and IL-22 compared with infected mice
      unexposed to indomethacin. CONCLUSION: These results demonstrate a negative
      impact of nonsteroidal anti-inflammatory drugs on antibiotic-associated CDI in
      mice and suggest that targeting the synthesis or signaling of prostaglandins
      might be an approach to ameliorating the severity of CDI.

PMID- 30238774
TI  - Bactericidal synergism between antibiotics and phage endolysin Cpl-711 to kill
      multidrug-resistant pneumococcus.
AB  - AIM: To test the synergistic effect of Cpl-711 endolysin and antibiotics for
      antipneumococcal activity. MATERIALS & METHODS: A combination of Cpl-711 and
      different antibiotics (amoxicillin, cefotaxime, levofloxacin and vancomycin) was
      tested in a checkerboard assay against several multidrug-resistant Streptococcus
      pneumoniae strains. Mouse and zebrafish models of pneumococcal sepsis were used
      to confirm the in vitro data. RESULTS: The activity of Cpl-711 combined with
      amoxicillin or cefotaxime was synergistic in the bactericidal effect against a
      serotype 23F multiresistant clinical isolate of S. pneumoniae. Synergy between
      Cpl-711 and cefotaxime was validated using both mouse and zebrafish models.
      CONCLUSION: Combination of Cpl-711 and cefotaxime may help in the treatment of
      diseases caused by multiresistant pneumococcal strains.

PMID- 30238775
TI  - The virulence of Legionella pneumophila is positively correlated with its ability
      to stimulate NF-kappaB activation.
AB  - AIM: Our work is to study the correlation between the virulence of different
      Legionella pneumophila in mouse model and its ability to activate NF-kappaB
      signaling pathway in vitro. MATERIALS & METHODS: We measured the abilities of
      different strains of L. pneumophila to induce the activation of NF-kappaB
      signaling pathway in vitro. By using A/J mice, we also detected the virulence of
      different strains in vivo. RESULTS & CONCLUSION: We demonstrated that different
      strains of L. pneumophila induce different levels of activation to NF-kappaB
      signaling pathway in vitro. We also found that L. pneumophila strain induced
      higher NF-kappaB activation in vitro showed more severe weight losses, higher
      mortality, more severe lung inflammation and higher levels of serum cytokines
      production in mice.

PMID- 30238777
TI  - Getting to the marrow of trained immunity.

PMID- 30238776
TI  - Folate and epigenetics: why we should not forget bacterial biosynthesis.

PMID- 30238778
TI  - Pathological buying symptoms are associated with distortions in judging elapsed
      time.
AB  - BACKGROUND AND AIMS: Pathological buying (PB) is often assumed to be related to
      deficits in impulse control. Distortions in judging elapsed time are one
      component of behavioral impulsivity. This study was set out to examine the
      hypothesis that PB propensity is associated with distorted time perception, such
      that time is perceived to pass more slowly. METHODS: The study is based on a
      convenience sample of 78 adults. Symptom severity of PB and related
      problems/disorders (substance use, borderline, depression, mania, and obsessive
      compulsive disorder) as well as four dimensions of trait impulsivity were
      assessed. A time-production task was employed that required participants to
      produce prespecified time intervals ranging from 1 to 60 s. RESULTS: PB
      propensity was associated with the belief that time elapses more slowly, even
      when controlling for symptoms of related disorders and general trait impulsivity.
      Neither trait impulsivity nor symptoms of related disorders were predictive of
      distortions in judging elapsed time. DISCUSSION AND CONCLUSION: These results
      suggest that PB propensity is related with non-specific, general deficits in
      judging elapsed time as a specific component of behavioral impulsivity.

PMID- 30238779
TI  - A study on the relationship between exercise addiction, abnormal eating
      attitudes, anxiety and depression among athletes in Israel.
AB  - BACKGROUND AND AIMS: The aim of this study was to investigate the relationship
      between exercise addiction, abnormal eating attitudes, anxiety, and depression
      among competitive and amateur athletes. METHODS: Participants were 100 athletes
      of mean age 28.3 years (18-62), of which there were 67 males and 35 females. The
      sample consisted of competitive and amateur athletes who participated in
      individual and group sports. They filled in the Exercise Addiction Inventory,
      Body Shape Questionnaire, a questionnaire assessing Eating Attitudes Test,
      Spielberger State-Trait Anxiety Inventory, and Beck Depression Inventory (BDI).
      RESULTS: Ratings of exercise addiction were positively correlated with BDI scores
      across the study sample. Exercise addiction ratings were associated with abnormal
      eating attitudes, but not with trait or state anxiety. Athletes engaging in
      individual sports scored marginally higher on depression scores than group
      athletes but there was no difference in depression scores between competitive and
      amateur athletes. Multiple regression analysis revealed that abnormal eating
      attitudes contributed significantly to ratings of exercise addiction and
      explained 7.7% of the variance. According to the Sobel test, the difference in
      the association between exercise addiction and eating disorder was significant.
      Therefore, body shape was a mediating factor between eating disorder and exercise
      addiction. DISCUSSION AND CONCLUSIONS: This study extends our preliminary
      findings of an association between exercise addiction and depression. Second,
      abnormal eating attitudes may explain most of the variance of exercise addiction.
      This is a further support for previous evidence of comorbidity between exercise
      addiction and eating disorders.

PMID- 30238780
TI  - The use of naltrexone in pathological and problem gambling: A UK case series.
AB  - BACKGROUND AND AIMS: To investigate the potential indications and adverse effects
      of using the opioid antagonist naltrexone to treat problem gamblers. CASE
      PRESENTATION: The files of the 1,192 patients who were referred to the National
      Problem Gambling Clinic between January 2015 and June 2016 were audited.
      Seventeen patients were considered appropriate for treatment with naltrexone,
      having attended and failed to respond to psychological therapies at the clinic.
      Fourteen patients were placed on a regimen of 50 mg/day naltrexone. DISCUSSION:
      Of the 14 patients who were treated with naltrexone, there were 10 for whom
      sufficient follow-up existed to analyze the treatment efficacy and side effects
      of naltrexone. Patients showed significant decreases in their craving to gamble
      and the majority (60%) were able to abstain completely from gambling in the
      treatment period, with a further 20% reducing their gambling to almost nothing.
      The reported side effects from the naltrexone included: loss of appetite,
      gastrointestinal pain, headaches, sedation, dizziness, and vivid dreams. Two
      patients with concurrent alcohol-use disorder relapsed during the treatment. One
      patient relapsed after the treatment period. CONCLUSIONS: The study showed
      significant outcomes in reducing gambling cravings for the sample set. Given the
      design of the study as a case series, there was no control group, and a number of
      patients were on other psychotropic medications. We recommend care when
      prescribing to those suffering from concurrent alcohol-use disorder.

PMID- 30238781
TI  - Guidelines and clinical practice at the primary level of healthcare in patients
      with type 2 diabetes mellitus with and without kidney disease in five European
      countries.
AB  - BACKGROUND: The number of patients with type 2 diabetes mellitus and diabetes
      mellitus-associated chronic kidney disease varies considerably between countries.
      Next to differences in genetic as well as life style risk factors, varying
      practices in medical care delivery might cause this diversity. METHOD: The
      PROVALID study recruited 4000 patients with type 2 diabetes mellitus at the
      primary level of healthcare in five European countries (Austria, Hungary, The
      Netherlands, Poland and Scotland). Baseline data were used to describe patient
      characteristics and compare the adherence to ADA (American Diabetes Association)
      and KDIGO (Kidney Disease: Improving Global Outcomes) guidelines with respect to
      metabolic and blood pressure control, use of renin-angiotensin system-blocking
      agents, statins and acetylsalicylic acid between the countries. RESULTS: About
      34.8% of the population had evidence of diabetes mellitus-associated chronic
      kidney disease. The median HbA1c level of the cohort was 6.8% (ranging from 6.5
      in Poland to 7.0% in Scotland). Mean blood pressure was 136/79 (+/-17/10) and
      significantly higher in subjects with elevated albuminuria. These individuals
      also were more often treated with renin-angiotensin system-blocking agents (74.1%
      vs 84.6%), whereas the use of statins was driven by cardiovascular comorbidity.
      Acetylsalicylic acid was used in only 28.9% subjects. Despite similar
      cardiovascular comorbidities and renal function, the use of renin-angiotensin
      system-blocking agents varied significantly between the countries from 66.7% to
      87.4%. An even higher variability was observed for patients >40 years of age
      using statins (39.8%-82.7%) and administration of acetylsalicylic acid in
      patients older than 50 years (5.2%-43.8%). CONCLUSION: Our study shows that
      medical practice in type 2 diabetes mellitus patients with and without renal
      disease is different in European countries. Longitudinal follow-up will reveal if
      this diversity affects clinical endpoints.

PMID- 30238784
TI  - The relationship between body dysmorphic disorder and obsessive-compulsive
      disorder: A systematic review of direct comparative studies.
AB  - OBJECTIVE:: Current nosology conceptualises body dysmorphic disorder as being
      related to obsessive-compulsive disorder, but the direct evidence to support this
      conceptualisation is mixed. In this systematic review, we aimed to provide an
      integrated overview of research that has directly compared body dysmorphic
      disorder and obsessive-compulsive disorder. METHOD:: The PubMed database was
      searched for empirical studies which had directly compared body dysmorphic
      disorder and obsessive-compulsive disorder groups across any subject matter. Of
      379 records, 31 met inclusion criteria and were reviewed. RESULTS:: Evidence of
      similarities between body dysmorphic disorder and obsessive-compulsive disorder
      was identified for broad illness features, including age of onset, illness
      course, symptom severity and level of functional impairment, as well as high
      perfectionism and high fear of negative evaluation. However, insight was clearly
      worse in body dysmorphic disorder than obsessive-compulsive disorder, and
      preliminary data also suggested unique visual processing features, impaired
      facial affect recognition, increased social anxiety severity and overall greater
      social-affective dysregulation in body dysmorphic disorder relative to obsessive
      compulsive disorder. CONCLUSION:: Limitations included a restricted number of
      studies overall, an absence of studies comparing biological parameters (e.g.
      neuroimaging), and the frequent inclusion of participants with comorbid body
      dysmorphic disorder and obsessive-compulsive disorder. Risks of interpreting
      common features as indications of shared underlying mechanisms are explored, and
      evidence of differences between the disorders are placed in the context of
      broader research findings. Overall, this review suggests that the current
      nosological status of body dysmorphic disorder is somewhat tenuous and requires
      further investigation, with particular focus on dimensional, biological and
      aetiological elements.

PMID- 30238783
TI  - Problem gambling and family violence: Findings from a population-representative
      study.
AB  - BACKGROUND AND AIMS: Few studies have investigated the association between
      problem gambling (PG) and violence extending into the family beyond intimate
      partners. This study aimed to explore the association between PG and family
      violence (FV) in a population-representative sample. It was hypothesized that:
      (a) PG would be positively associated with FV, even after adjusting for
      sociodemographic variables and comorbidities and (b) these relationships would be
      significantly exacerbated by substance use and psychological distress. A
      secondary aim was to explore whether gender moderated these relationships.
      METHODS: Computer-assisted telephone interviews were conducted with a population
      representative sample of 4,153 Australian adults. RESULTS: Moderate-risk
      (MR)/problem gamblers had a 2.73-fold increase in the odds of experiencing FV
      victimization (21.3%; 95% CI: 13.1-29.4) relative to non-problem gamblers (9.4%;
      95% CI: 8.5-10.4). They also had a 2.56-fold increase in the odds of experiencing
      FV perpetration (19.7%; 95% CI: 11.8-27.7) relative to non-problem gamblers
      (9.0%; 95% CI: 8.0-10.0). Low-risk gamblers also had over a twofold increase in
      the odds of experiencing FV victimization (20.0%; 95% CI: 14.0-26.0) and
      perpetration (19.3%; 95% CI: 13.5-25.1). These relationships remained robust for
      low-risk gamblers, but were attenuated for MR/problem gamblers, after adjustment
      for substance use and psychological distress. MR/problem gamblers had a greater
      probability of FV victimization, if they reported hazardous alcohol use; and low
      risk gamblers had a greater probability of FV perpetration if they were female.
      DISCUSSION AND CONCLUSION: These findings provide further support for routine
      screening, highlight the need for prevention and intervention programs, and
      suggest that reducing alcohol use may be important in these efforts.

PMID- 30238786
TI  - A public health catastrophe looms: The Australian and New Zealand prison crisis.

PMID- 30238785
TI  - Clustering of treatment-seeking women with gambling disorder.
AB  - BACKGROUND: The prevalence of gambling disorder (GD) in women has increased, but,
      to date, few studies have explored the features of clinical GD subtypes in female
      samples. AIMS: The aim of this study is to identify empirical clusters based on
      clinical/sociodemographic variables in a sample of treatment-seeking women with
      GD. METHODS: Agglomerative hierarchical clustering was applied to a sample of n =
      280 patients, using sociodemographic variables, psychopathology, and personality
      traits as indicators for the grouping procedure. RESULTS: Three mutually
      exclusive groups were obtained: (a) Cluster 1 (highly dysfunctional; n = 82,
      29.3%) endorsed the highest levels in gambling severity, comorbid
      psychopathology, novelty seeking, harm avoidance, and self-transcendence, and the
      lowest scores in self-directedness and cooperativeness; (b) Cluster 2
      (dysfunctional; n = 142, 50.7%) achieved medium mean scores in gambling severity
      and psychopathological symptoms; and (c) Cluster 3 (functional; n = 56, 20.0%)
      obtained the lowest mean scores in gambling severity and in psychopathology, and
      a personality profile characterized by low levels in novelty seeking, harm
      avoidance, and self-transcendence, and the highest levels in self-directedness
      and cooperativeness. DISCUSSION AND CONCLUSIONS: This study sheds light on the
      clinical heterogeneity of women suffering from GD. Identifying the differing
      features of women with GD is vital to developing prevention programs and
      personalized treatment protocols for this overlooked population.

PMID- 30238782
TI  - Allele-specific methylation of imprinted genes in fetal cord blood is influenced
      by cis-acting genetic variants and parental factors.
AB  - AIM: To examine the effects of genetic variation, parental age and BMI on
      parental allele-specific methylation of imprinted genes in fetal cord blood
      samples. METHODOLOGY: We have developed SNP genotyping and deep bisulphite
      sequencing assays for six imprinted genes to determine parental allele-specific
      methylation patterns in diploid somatic tissues. RESULTS: Multivariate linear
      regression analyses revealed a negative correlation of paternal age with paternal
      MEG3 allele methylation in fetal cord blood. Methylation of the maternal PEG3
      allele showed a positive correlation with maternal age. Paternal BMI was
      positively correlated with paternal MEST allele methylation. In addition to
      parental origin, allele-specific methylation of most imprinted genes was largely
      dependent on the underlying SNP haplotype. CONCLUSION: Our study supports the
      idea that parental factors can have an impact, although of small effect size, on
      the epigenome of the next generation, providing an additional layer of complexity
      to phenotypic diversity.

PMID- 30238787
TI  - Maladaptive daydreaming as a new form of behavioral addiction.
AB  - BACKGROUND AND AIMS: Maladaptive daydreaming (MD) has many features of behavioral
      addiction, but research exploring this syndrome is limited. This case study
      provides a qualitative exploration of MD. METHODS: A structured clinical
      interview and mental state examination of a patient with MD were video-recorded
      and transcribed verbatim. Transcripts were subjected to the interpretative
      phenomenological analysis. RESULTS: MD was developed as a strategy to cope with
      distress but led to uncontrollable absorption in fantasy, social withdrawal, and
      neglecting aspects of everyday life. It was coupled with excessive Internet use
      and viewing porn. DISCUSSION AND CONCLUSIONS: Patients should be questioned about
      MD during clinical assessment. Further studies are necessary to determine whether
      MD constitutes a separate syndrome or is a part of other behavioral addictions.

PMID- 30238788
TI  - Relationship between attention-deficit hyperactivity disorder symptoms and
      problem gambling: A mediation analysis of influential factors among 7,403
      individuals from the UK.
AB  - BACKGROUND AND AIMS: Our goal was to examine the association between attention
      deficit hyperactivity disorder (ADHD) symptoms and gambling problems, and to
      identify potential mediating factors of this association. METHODS: This study
      used cross-sectional, community-based data from 7,403 people aged >=16 years who
      participated in the Adult Psychiatric Morbidity Survey 2007. ADHD symptoms were
      assessed using the Adult ADHD Self-Report Scale (ASRS) Screener. Problem gambling
      was assessed using a questionnaire based on the 10 DSM-IV diagnostic criteria for
      pathological gambling. Respondents were classified as having no problem, at-risk,
      or problem gambling. Logistic regression and mediation analyses were conducted to
      analyze the association between ADHD symptoms (i.e., ASRS score >=14) and problem
      gambling and the role of several variables in this association. RESULTS: The
      prevalence of at-risk (5.3% vs. 2.4%) and problem gambling (2.4% vs. 0.6%) was
      higher in individuals with ADHD symptoms than in those without ADHD symptoms.
      ADHD symptoms were significantly associated with both at-risk (OR = 2.15; 95% CI
      = 1.22-3.79) and problem gambling (OR = 3.57; 95% CI = 1.53-8.31) when adjusted
      for age, sex, and ethnicity. Common mental disorders (CMDs; i.e., depression and
      anxiety disorders) (mediated percentage = 22.4%), borderline personality disorder
      (BPD) traits (22.1%), stressful life events (13.2%), stress at work or home
      (12.6%), alcohol dependence (11.8%), and impulsivity (11.2%) were significant
      mediators in the ADHD-gambling association. DISCUSSION AND CONCLUSIONS: Overall,
      ADHD symptoms were positively associated with problem gambling. CMDs, BPD traits,
      and stressful life events were important mediators in this relationship.

PMID- 30238789
TI  - Time to call for a global public health approach in prevention of the onset and
      progression of problematic gaming.
AB  - Problematic video gaming is a global problem. Policy and programs responses to
      the problem vary among countries, partly due to cultural differences in the east
      and the west, meaning that caution is needed in drawing comparisons. Promoting
      parental education and positive youth development would be a useful approach to
      curb problematic behavior among children and adolescents. We suggest using a
      public health approach, based on our experience in dealing with commodities,
      which are harmful to health.

PMID- 30238790
TI  - Correlation of Exhaled Nasal Nitric Oxide With Sinus Computed Tomography and
      Sinonasal Outcome Test Scores: A Cross-sectional Pilot Study.
AB  - BACKGROUND: Computed tomography (CT) of the paranasal sinuses is the diagnostic
      reference standard for chronic rhinosinusitis and related inflammatory sinus
      pathology. Nasal nitric oxide (nNO) levels have been investigated as a diagnostic
      tool in sinus disease because it decreases with sinus obstruction. OBJECTIVE: The
      primary aim of the study was to determine the correlation of passive (baseline)
      and dynamic (humming) nNO to CT findings of sinus inflammation and to sinonasal
      symptoms measured by the modified Sinonasal Outcome Test (26 items) (SNOT-26).
      METHODS: From June 2015 through January 2016, subjects had baseline and humming
      nNO levels measured with a chemiluminescence NO analyzer, and each subject
      underwent CT imaging and completed the SNOT-26 survey. CT images were scored
      using the Lund-Mackay (LM) system (LM scores >3 indicated sinus inflammation).
      Correlation was measured by linear and ordinal regression analysis that compared
      SNOT-26 scores, LM scores, and nNO measurements. RESULTS: Fourteen subjects were
      recruited. LM scores had a positive pairwise correlation with total SNOT-26
      scores ( R2 = .1457; correlation = .3817) and nasal-specific SNOT-26 scores ( R2
      = .4036; correlation = .6353). Baseline nasal nNO scores had a negative pairwise
      correlation with LM scores ( R2 = .1580; correlation = -.3582), total SNOT-26
      scores ( R2 = .1515; correlation = -.3893), and nasal-specific SNOT-26 scores (
      R2 = .0805; correlation = -.4343). Although baseline nNO levels correlated with
      LM and SNOT-26 scores, humming nNO levels did not show a similar correlation.
      CONCLUSION: Baseline passive nNO may be a useful and inexpensive point-of-care
      screening test for sinonasal opacification.

PMID- 30238791
TI  - Don't throw the baby out with the bathwater: A case for bipolar II.

PMID- 30238792
TI  - The economic and humanistic burden of patients in receipt of current available
      therapies for nAMD.
AB  - AIM: To determine the economic and humanistic burden of neovascular age-related
      macular degeneration (nAMD) in a cohort of patients treated with anti-VEGF in
      Europe and the US. PATIENTS & METHODS:  79 respondents from the EU and 63 from
      the US with a self-reported diagnosis of nAMD and in current receipt of
      treatment, as reported in an international, general population survey, were
      compared with non-nAMD controls. RESULTS: Anti-VEGF-treated nAMD patients in the
      EU had a greater utilization of healthcare resources, poorer quality of life and
      greater overall activity impairment versus non-nAMD controls. In the US cohort,
      treated nAMD patients had significantly greater resource utilization for
      ophthalmologist visits only. CONCLUSION: The burden of care associated with nAMD
      on EU and US healthcare systems, and on patients who are in receipt of nAMD
      therapy, is significant and likely to be unsustainable.

PMID- 30238793
TI  - Association between Federally Qualified Health Center usage and emergency
      department utilization among California's HIV-infected Medicaid beneficiaries,
      2009.
AB  - Federally Qualified Health Centers (FQHCs) have long been important sources of
      care for publicly insured people living with HIV. FQHC users have historically
      used emergency departments (EDs) at a higher-than-average rate. This paper
      examines whether this greater use relates to access difficulties in FQHCs or to
      characteristics of FQHC users. Zero-inflated Poisson models were used to estimate
      how FQHC use related to the odds of being an ED user and annual number of ED
      visits, using claims data on 6,284 HIV-infected California Medicaid beneficiaries
      in 2008-2009. FQHC users averaged significantly greater numbers of annual ED
      visits than non-FQHC users and those with no outpatient usage (1.89, 1.59, and
      1.70, respectively; P = 0.043). FQHC users had higher odds of being ED users (OR
      = 1.14; 95%CI 1.02-1.27). In multivariable analyses, FQHC clients had higher odds
      of ED usage controlling for demographic and service characteristics (OR = 1.15;
      95%CI 1.02-1.30) but not when medical characteristics were included (OR = 1.08;
      95%CI 0.95-1.24). Among ED users, FQHC use was not significantly associated with
      the number of ED visits in our models (rate ratio (RR) = 1.00; 95%CI 0.87-1.15).
      The overall difference in mean annual ED visits observed between FQHC and non
      FQHC groups was reduced to insignificance (1.75; 95% CI 1.59-1.92 vs 1.70; 95%CI
      1.54-1.85) after adjusting for demographic, service, and medical characteristics.
      Overall, FQHC users had higher ED utilization than non-FQHC users, but the
      disparity was largely driven by differences in underlying medical
      characteristics.

PMID- 30238794
TI  - Influences of addition of malic acid or citric acid, Lactobacillus plantarum and
      their mixtures on fermentation quality, proteolysis and fatty acid composition of
      ensiled alfalfa.
AB  - The aim of this study was to evaluate the effect of two organic acids [malic acid
      (MA) and citric acid (CA)], Lactobacillus plantarum (LP) and their mixtures on
      the fermentation of alfalfa silage. The wilted and chopped alfalfa was ensiled in
      vacuum-sealed plastic bags (200-230 g per bag) with following additives: 0.5%
      distilled water (control), 0.5% DL-MA, 0.5% CA, LP (1 . 106 cfu/g), 0.5% DL-MA
      plus LP (MA+LP) or 0.5% CA plus LP (CA+LP) (application rates based on fresh
      weight). Each treatment had four replicates and was stored at room temperature.
      After 60 d of ensiling, decreases in pH, non-protein N (NPN) and increases in
      lactic acid were observed in all additive-treated silages (p < 0.01). Compared
      with treatment LP, higher pH and lower lactic acid concentrations were observed
      after MA or CA addition (p < 0.05) and further application of MA or CA together
      with LP did not promote lactic acid fermentation in ensiled alfalfa. Furthermore,
      additives decreased the proportion of saturated fatty acids and increased the
      proportion of polyunsaturated fatty acids in ensiled alfalfa, with the highest
      level in CA-treated silages (p < 0.05). Although MA and CA were not as effective
      as LP in improving silage fermentation quality, treatments MA+LP and CA+LP were
      more effective in decreasing silage NPN, and CA was most effective in inhibiting
      biohydrogenation of fatty acids in ensiled alfalfa.

PMID- 30238795
TI  - From substance to process: A meta-ethnographic review of how healthcare
      professionals and patients understand placebos and their effects in primary care.
AB  - Research suggests that a 'placebo' can improve conditions common in primary care
      including pain, depression and irritable bowel syndrome. However, disagreement
      persists over the definition and clinical relevance of placebo treatments. We
      conducted a meta-ethnographic, mixed-research systematic review to explore how
      healthcare professionals and patients understand placebos and their effects in
      primary care. We conducted systematic literature searches of five databases -
      augmented by reference chaining, key author searches and expert opinion - related
      to views on placebos, placebo effects and placebo use in primary care. From a
      total of 34 eligible quantitative, qualitative and mixed-methods articles
      reporting findings from 28 studies, 21 were related to healthcare professionals'
      views, 11 were related to patients' views and two were related to both groups. In
      the studies under review, healthcare professionals reported using placebos at
      markedly different frequencies. This was highly influenced by how placebos were
      defined in the studies. Both healthcare professionals and patients predominantly
      defined placebos as material substances such as 'inert' pills, despite this
      definition being inconsistent with current scientific thinking. However,
      healthcare professionals also, but less prevalently, defined placebos in a
      different way: as contextual processes. This better concurs with modern placebo
      definitions, which focus on context, ritual, meaning and enactivism. However,
      given the enduring ubiquity of substance definitions, for both healthcare
      professionals and patients, we question the practical, clinical validity of
      stretching the term 'placebo' towards its modern iteration. To produce 'placebo
      effects', therefore, primary healthcare professionals may be better off
      abandoning placebo terminology altogether.

PMID- 30238796
TI  - Association of Dairy Protein Intake During Pregnancy with Birth Weight.
AB  - BACKGROUND: One in 4 children globally is stunted. Stunting is associated with
      reduced cognitive development, reduced productivity, and chronic disease in later
      life. OBJECTIVE: To explore the association between maternal diet during
      pregnancy and low birth weight, which increases the risk of stunting. METHODS:
      Current literature pertaining to maternal diet and low birth weight was reviewed.
      RESULTS: Low birth weight and small for gestational age are risk factors for
      stunting. Dietary pattern studies show an association between moderate dairy
      protein intake and increased birth weight and reduced risk of low birth weight.
      Protein-to-carbohydrate ratios are important factors in relation to gestational
      weight gain and fetal programming. There is evidence suggesting that whey protein
      could play a role in fetal lean body mass and reduced risk of low birth weight.
      CONCLUSIONS: Maternal diet is associated with birth weight.

PMID- 30238797
TI  - Addressing the Double Burden of Malnutrition in Developing Countries: Need for
      Strategies to Improve the Lean Body Mass.
AB  - The double burden of childhood undernutrition and adult-onset adiposity-related
      chronic diseases is a key concern in many developing countries that are currently
      undergoing epidemiological and nutrition transition. Impaired linear growth with
      suboptimal lean body mass development seems to be the link between these 2
      seemingly contrasting forms of malnutrition. Studies assessing the role of early
      nutrition in the later lean body mass development have shown consistent positive
      association. In addition, the nutrition during life course, especially the
      dietary intake of protein, zinc, calcium, and vitamin D status, impacts the lean
      body mass. Promoting increased intake of these important nutrients throughout
      life course would, therefore, be important for optimal development and
      maintenance of lean body mass. Diversified diets with increased consumption of
      nutrient-rich foods, especially milk and other animal source foods, are crucial
      for the development of optimal body composition and alleviation of the double
      burden of malnutrition.

PMID- 30238799
TI  - Useful Tools for Food Aid: Linear Programming and Protein Quality Tools.
AB  - The development of a superior treatment option for severe acute malnutrition
      (SAM) which allowed for home-based therapy put in place constraints that are
      crucial for ensuring the feasibility and nutritional integrity of the treatment.
      Soon after the initial success of ready-to-use therapeutic food (RUTF), there
      were attempts to modify the formulation for cost and other areas of
      acceptability. While alternative formulations have been taken on in clinical
      trials, they have been inferior to the standard RUTF recipe. Linear programming
      (LP) technology, however, has streamlined the formulation process allowing the
      user to account for the crucial constraints required to maintain the feasibility
      and nutritional integrity of standard RUTF. With the aid of an LP tool and other
      functional tools for assessing nutrient quality, nutrition researchers can use
      innovative approaches in food development that could potentially revolutionize
      food aid products.

PMID- 30238798
TI  - Maximizing Recovery and Growth When Treating Moderate Acute Malnutrition with
      Whey-Containing Supplements.
AB  - BACKGROUND: Much debate exists about the utility of dairy ingredients in the
      supplementary foods used to treat childhood moderate acute malnutrition (MAM).
      OBJECTIVE: To review the evidence regarding the effectiveness of dairy-containing
      supplements, particularly specially formulated foods containing whey permeate and
      whey protein concentrate, in treating children with MAM. METHODS: A summary of a
      conference presentation regarding an overview of current evidence behind the use
      of whey in supplementary foods, including results of a randomized double-blinded
      clinical effectiveness trial involving 2259 Malawian children treated for MAM
      using either a soy ready-to-use supplementary food (RUSF) or a novel whey RUSF
      treatment. RESULTS: While the majority of the evidence base only suggests
      potential benefits of including whey in supplementary foods to treat MAM, a
      recent study specifically demonstrates that a whey RUSF produced superior
      recovery and growth outcomes in treating children with MAM when compared with a
      soy RUSF. CONCLUSIONS: The use of whey ingredients has been shown to improve
      outcomes in the treatment of MAM; however, further research is needed to identify
      the ideal amount and type of dairy protein required to produce the best outcomes
      for the lowest cost.

PMID- 30238800
TI  - Dairy Sector Paves the Way to Inclusive Growth and Nutrition in Emerging Markets.
AB  - This manuscript is an opinion editorial, which summarizes the presentation given
      at the Dairy Nutrition: An Engine for Economic Growth conference.

PMID- 30238801
TI  - Higher Levels of Dairy Result in Improved Physical Outcomes: A Synthesis of 3
      Randomized Controlled Trials in Guinea-Bissau Comparing Supplements with
      Different Levels of Dairy Ingredients Among Children 6 to 59 Months, 5 to 19 Year
      Olds, and Mothers in Preschools, Primary Schools, and Villages, and the
      Implications for Programs.
AB  - BACKGROUND: This article synthesizes the results of 3 cluster randomized
      controlled trials of dairy-containing ready-to-use supplementary foods (RUSFs) to
      address malnutrition in primary schools, preschools and villages in Guinea
      Bissau, one of the world's poorest countries. Together, these studies document
      widespread malnutrition across infants, young children, adolescents, and pregnant
      and lactating women and point to intervention options that were not previously
      presented. OBJECTIVE: To combine the evidence from the United States Department
      of Agriculture-funded pilot studies in Guinea-Bissau on the effects of dairy
      protein supplementation to gain a broader perspective on the role of dairy
      containing RUSFs in various age-groups, the importance of the mother-child dyad
      and family food dynamics for infant and child growth. Translate the results into
      action and the next generation of effective products. METHODS: A comparative
      analysis of data and synthesis of evidence from 3 published studies and ongoing
      research conducted by our team in Guinea-Bissau. RESULTS AND CONCLUSIONS: Higher
      dairy supplements have the potential to achieve broad benefits for malnutrition,
      especially in mothers and early childhood (first 1000 days and 36-59 months).
      Higher levels of dairy protein also can prevent moderate acute malnutrition in
      children younger than 2 years, independent of the family food dynamic. Community
      level nutrition behavior change education should target older children and
      adolescents at the community level and through the preschool/school platform.

PMID- 30238802
TI  - Conference Proceedings: Dairy Nutrition, An Engine for Economic Growth.
AB  - The U.S. Dairy Export Council's Dairy for Global Nutrition Initiative hosted a
      conference titled, "Dairy Nutrition: An Engine for Economic Growth," held on May
      10 to 11, 2017, at the Boise Center in Boise, Idaho. Speakers explored the role
      of dairy products in mitigating malnutrition, stimulating local economies, and
      promoting better health, globally.

PMID- 30238803
TI  - Mapping Nutrition Interventions, a Key Analytical Tool for Informing the
      Multisectoral Planning Process: Example From Burkina Faso.
AB  - BACKGROUND: The government of Burkina Faso, along with the United Nations Network
      for Nutrition (UNN), activity REACH (Renewed Efforts Against Child Hunger and
      undernutrition) partnership, conducted a mapping of nutrition interventions and
      stakeholders to identify the best approaches for scaling up priority nutrition
      interventions and to strengthen a multisectoral response to fight malnutrition.
      OBJECTIVE: The objectives include describing the process used to map a set of
      country-prioritized nutrition interventions and to describe how the results
      contributed to the multisectoral nutrition planning process in Burkina Faso.
      METHODS: The mapping exercise was designed as a cross-sectional study using the
      Excel-based Scaling Up Nutrition Planning and Monitoring Tool (SUN PMT) to
      collect, store, and analyze data. RESULTS: The results present different analyses
      produced by the SUN PMT for 29 prioritized nutrition interventions. The analyses
      include the distribution of nutrition stakeholders for each intervention, the
      calculation of geographic and population coverage for each intervention, and the
      utilization of delivery mechanisms to reach beneficiaries. CONCLUSIONS: The
      mapping of key nutrition interventions and stakeholders supporting those
      interventions in Burkina Faso was an important tool in the multisectoral planning
      process. The exercise made it possible to identify gaps and needs; launch a
      discussion on nutrition planning and the scaling up of interventions; and
      mobilize sectors and development partners around nutrition.

PMID- 30238804
TI  - A Qualitative Examination of the Experiences of Veterans Treatment Court
      Graduates in Allegheny County, Pennsylvania.
AB  - U.S. Veterans treatment courts (VTCs) serve justice-involved Veterans with
      behavioral health and reintegration issues. However, there is paucity of efforts
      examining VTC participants' experiences and distinguishing the unique operations
      of VTCs. We summarize a descriptive history of a large VTC program in a major
      metropolitan area (Pittsburgh, Pennsylvania) and examine the experiences of this
      VTC's participants. We used content analysis to code VTC graduation proceeding
      transcripts with complementary content data from resources distributed by the
      presiding Judge to entering participants. From 2009 through 2016, 118 Veterans
      were graduated, averaging 9 to 12 months for completion for those with felony or
      non-felony charges, and blended monitoring with positive reinforcement within a
      three-stage program. From 62 VTC graduates across eight graduations, testimonies
      centered on gratitude toward the treatment team, treatment readiness, treatments
      received, and reintegration. As several theoretical frameworks on behavior change
      exist, opportunities remain to enhance the delivery of the VTC.

PMID- 30238805
TI  - Z-scores of early diastolic blood flow widths of mitral and tricuspid valves in
      normal fetuses and fetuses with dilated coronary sinus.
AB  - OBJECTIVES: To establish Z-score models for early diastolic blood flow widths of
      mitral and tricuspid valves in normal fetuses and compare Z-scores and other
      blood flow dynamic parameters between normal fetuses and fetuses with dilated
      coronary sinus (CS). This study seeks to assess whether dilated CS affects
      cardiac structure or hemodynamics. METHODS: One hundred twenty-nine normal
      fetuses (Group I) and 15 fetuses with dilated CS connected to persistent left
      superior vena cava (PLSVC) (Group II) were included in this study. Noncardiac
      biometrical parameters, including gestation age (GA), biparietal diameter (BPD),
      femoral length (FL), and heart area (HA), were obtained. Hemodynamic parameters,
      such as the early diastolic blood flow widths of mitral and tricuspid valves (MV
      CDFI-Width, TV-CDFI-Width), velocity and time integral of blood flow (VTI), peak
      early and late diastolic velocity of mitral and tricuspid valves [peak early
      diastolic velocity of the mitral valve (MVE), peak late diastolic velocity of the
      mitral valve (MVA), peak early diastolic velocity of the tricuspid valve (TVE),
      peak late diastolic velocity of the tricuspid valve (TVA)], were measured.
      RESULTS: Z-score models for MV-CDFI-Width and TV-CDFI-Width against noncardiac
      biometrical parameters were best described by linear regression analysis. The
      mean equations of MV-CDFI-Width against noncardiac biometrical parameters were
      0.066 + (0.025 * GA), 0.169 + (0.084 * BPD), 0.213 + (0.106 * FL) and 0.533 +
      (0.028 * HA). The SD for MV-CDFI-Width against FL was estimated based on values
      from the following equation: -0.006 + (0.02 * FL). Other SDs were constants
      estimated as the standard deviations of the unscaled residuals. Z-scores and
      other blood flow dynamic parameters exhibited no statistically significant
      differences between Group I and Group II. CONCLUSIONS: This study demonstrated
      that dilated CS did not affect fetal hemodynamics of the mitral or tricuspid
      valves or cardiac structures. We also suggested that the causes of diminutive
      left heart or coarctation of the aorta might not be associated with dilated CS in
      fetuses with PLSVC.

PMID- 30238806
TI  - A comparison of treatment patterns, healthcare resource utilization, and costs
      among young adult Medicaid beneficiaries with schizophrenia treated with
      paliperidone palmitate or oral atypical antipsychotics in the US.
AB  - BACKGROUND: Much of the burden associated with schizophrenia is attributed to its
      early onset and chronic nature. Treatment with once monthly paliperidone
      palmitate (PP1M) is associated with lower healthcare utilization and better
      adherence as compared to oral atypical antipsychotics (OAAs). This study aimed to
      evaluate real-world effectiveness of PP1M and OAA therapies among US-based adult
      Medicaid patients with schizophrenia, overall and among young adults aged 18-35
      years. METHODS: Adult patients with a diagnosis of schizophrenia and at least two
      claims for PP1M or OAA between January 1, 2010 and December 31, 2014 were
      selected from the IBM Watson Health MarketScan Medicaid Database. Treatment
      patterns and healthcare resource utilization and costs were compared between PP1M
      and OAA treatment groups following inverse probability of treatment (IPT)
      weighting to adjust for potential differences. Utilization and cost outcomes were
      estimated using OLS and weighted Poisson regression models. RESULTS: After IPT
      weighting, the young adult PP1M and OAA cohorts were comprised of 3,095 and 3,155
      patients, respectively. PP1M patients had a higher duration of continuous
      treatment exposure (168.2 vs 132.5 days, p = .004) and better adherence on the
      index medication (proportion of days covered >=80%: 19.0% vs 17.1%, p < .049).
      Young adults treated with PP1M were 37% less likely to have an all-cause
      inpatient admission (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.53
      0.74) and 33% less likely to have an ER visit (OR = 0.67, 95% CI = 0.55-0.81)
      compared to OAA young adult patients, but 27% more likely to have an all-cause
      outpatient office visit (OR = 1.27, 95% CI = 1.02-1.56). PP1M patients incurred
      significantly lower medical costs as compared to OAA patients. CONCLUSIONS:
      Medicaid patients with schizophrenia treated with PP1M have higher medication
      adherence and have fewer hospitalizations as compared to patients treated with
      OAAs. PP1M may lead to reduced healthcare utilization and improved clinical
      outcomes.

PMID- 30238807
TI  - Pharmacogenomics/updated for precision medicine in dermatology.
AB  - Pharmacogenomics, a key part of precision medicine, has the potential to tailor
      drug therapy with the high safety margins and optimized response. Before the
      Human Genome Project in 2003, articles on pharmacogenomics were limited. The last
      15 years have seen significant growth in the field, with gene variant discoveries
      that play essential roles in individuals' drug response. Dermatology has started
      to take advantage of this information. This overview shows how pharmacogenomic
      databases have expanded in the treatment of skin diseases and provides a list of
      current dermatologic drugs with their FDA-approved biomarkers and clinical
      implementation.

PMID- 30238808
TI  - Exosome-carried microRNA-based signature as a cellular trigger for the evolution
      of chronic lymphocytic leukemia into Richter syndrome.
AB  - Even if considered a cumulative and not a proliferative CD5+ B-cell neoplasm,
      chronic lymphocytic leukemia (CLL) has a proliferation rate higher than that
      recognized earlier, especially in the lymphoid tissues. Some patients with CLL
      develop a clinical syndrome entitled Richter syndrome (RS). Understanding CLL
      genetics and epigenetics may help to elucidate the molecular basics of the
      clinical heterogeneity of this type of malignancy. In the present project we
      aimed to identify a microRNA species that can predict the evolution of therapy
      resistant CLL towards RS. In the first phase of our study, microRNA-19b was
      identified as a possible target, and in the second phase, we transfected three
      different CLL cell lines with microRNA-19b mimic and inhibitor and assessed the
      potential role on leukemia cells in vitro. The mechanism by which miR-19b acts
      were identified as the upregulation of Ki67 and downregulation of p53. This was
      further supported through RT-PCR and western blotting on CLL cell lines, as well
      as by next generation sequencing on two patients diagnosed with CLL that evolved
      into RS.

PMID- 30238809
TI  - Arterial stiffness during controlled ovarian hyperstimulation and early pregnancy
      in women exposed to assisted reproduction.
AB  - INTRODUCTION: Female sex hormones have vasorelaxing effects in non-pregnant and
      pregnant women. We aimed to investigate the effect of controlled ovarian
      hyperstimulation (COH) for in vitro fertilization (IVF), and early pregnancy, on
      arterial stiffness as assessed by digital pulse wave analysis (DPA),
      hypothesizing reduced arterial stiffness as an effect of increased estrogen
      levels. MATERIAL AND METHODS: A total of 68 women undergoing IVF were examined
      with DPA before conception and during IVF treatment with COH and embryo transfer
      (ET), and in gestational week seven in 19 women who became pregnant. Heart rate
      (HR), mean arterial pressure (MAP) and the DPA variables cardiac ejection
      elasticity index (EEI), b/a, dicrotic index (DI), d/a and aging index (AI) were
      measured. RESULTS: HR was significantly increased at all measuring points (p <=
      0.003) but MAP only at ET (p 0.007). DPA variables representing large arteries
      (EEI, b/a) and peripheral arteries (DI, but not d/a), and the global variable AI,
      indicated increased arterial stiffness at ET compared with baseline (p <= 0.035).
      No DPA variable was significantly changed at pregnancy measurements compared to
      baseline. CONCLUSION: During COH for IVF treatment, DPA showed no changes in
      arterial stiffness during the follicular phase or in early pregnancy, but
      increased arterial stiffness in central and peripheral arteries in the early
      luteal phase. The result suggests a hormonal hemodynamic activation counteracting
      the effects of estrogen.

PMID- 30238810
TI  - Epithelioid Hemangioendothelioma of the Bowel in Crohn's Disease: The First
      Reported Case.
AB  - BACKGROUND: Epithelioid hemangioendothelioma (EHE) is an uncommon malignant
      endothelial neoplasm that most commonly arises in soft tissue, bone, lung, and
      liver. Crohn's disease (CD) is an inflammatory bowel disease of unknown etiology
      that is frequently associated with complications including strictures,
      fistulas/fissures, and neoplasms. CASE DESCRIPTION: A 43-year-old woman with a 6
      year history of severe CD presented with anal pain and bleeding. She had prior
      partial colectomy for a stricture and a diverting ileostomy for perianal fissures
      and stricture. Colonoscopy showed severe chronic active colitis, stricture at 30
      cm of anal verge, and a perianal fistula. The patient underwent total
      proctocolectomy. The colonic mucosa exhibited segmental ulceration and irregular
      thickening of the colon wall. Beneath an ulcer of the anal canal within the
      muscularis propria was a 1.2-cm poorly circumscribed, firm, white-tan mass. The
      mass was composed of cords and groups of large epithelioid endothelial cells with
      intracytoplasmic vacuoles enmeshed in a myxohyaline stroma.
      Immunohistochemically, the tumor cells were positive for ERG, CD31, and CAMTA1
      and focally positive for keratin and SMA. Next-generation sequencing revealed a
      WWTR1-CMATA1 fusion. The morphology, immunoprofile, and molecular genetics were
      diagnostic of EHE. DISCUSSION: Long-standing inflammatory bowel disease is
      associated with significant risk for developing neoplasms, usually carcinomas,
      which can be indistinguishable radiologically and clinically from nonneoplastic
      complications. These tumors are often identified as an incidental finding in
      specimens resected for clinically severe disease. This is the first report of EHE
      arising in the bowel affected by CD, and it mimicked mural fibrosis and fissures.

PMID- 30238811
TI  - Patient Awareness of Association of Diabetes and Periodontal Disease.
AB  - This cross-sectional study sought to assess the current awareness, knowledge, and
      behavior regarding diabetes mellitus (DM) and periodontal disease (PD)
      association among a convenience sample of patients from a large Wisconsin-based
      integrated medical-dental health care organization serving largely rurally based
      communities. An anonymous 10-question survey was distributed at regional medical
      and dental centers of dental and medical clinics of a single health care
      institution over a 4-week period, to achieve a cross-sectional sampling of
      patients aged 18 to 80 years. Among 946 respondents, 616 were female. Patient
      reported periodicity for dental visits was highest between 6 months and 1 year
      (56.4%). Respondents reporting "poor-fair" knowledgeability surrounding DM-PD
      association correlated with highest interest in learning more about DM-PD
      relationship ( p <.0001). While over 80% of respondents correctly answered
      questions about gum disease symptomology and contribution of oral health
      practices on diabetes prevention, only 51% knew that PD affected blood sugar
      control. Willingness to comply with medical screening conducted by dental
      providers for diseases affecting oral health was indicated by 44% of respondents
      ( p < .0001). Study results indicated that knowledgeability levels among patients
      surrounding the effect of PD on DM needed improvement. Strategic educational
      interventions targeting improved health literacy among patients may further
      promote prevention of DM-PD complications. Health literacy gaps remain to be
      addressed in patient understanding of the importance of detecting and managing
      dysglycemia for maintenance of periodontal health, creating opportunities for
      patient education.

PMID- 30238812
TI  - Cultivating healthy trajectories: An experimental study of community gardening
      and health.
AB  - Advances in behavioral medicine suggest that optimal solutions to modern health
      challenges should be multifaceted, targeting multiple cognitions and behaviors
      simultaneously. Community gardening holds great promise as one such multifaceted
      intervention but lacks rigorous evidence of efficacy. We present one of the first
      experimental studies on the topic. The results revealed promise for aspects of
      community gardening, but also suggest the necessity for the use of rigorous
      methodologies moving forward. In addition, this article provides a framework for
      studying the effects of community gardening and similar multifaceted health
      promotion efforts.

PMID- 30238813
TI  - Economic burden of thromboembolic and hemorrhagic complications in non-valvular
      atrial fibrillation in Algeria (the ELRAGFA study).
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with
      substantial public health and economic impact on healthcare systems due to the
      prevention and management of thromboembolic and hemorrhagic complications. In
      Algeria, stroke is a leading cause of death, representing 15.6% of all deaths in
      2012. Current data on the epidemiology and costs associated with non-valvular AF
      (NVAF) in Algeria are not available. METHODS: A three-step approach was
      undertaken to estimate the economic burden of NVAF in Algeria. First, a
      literature review identified the epidemiological burden of the disease. Second,
      expert clinicians practicing in Algerian hospitals were surveyed on consumed
      resources and unit costs of treatment and management of complications and
      prevention. Finally, these data were combined with event probabilities in an
      economic model to estimate the annual cost of NVAF prevention and complications
      for the Algerian healthcare system. RESULTS: Based on literature and demographics
      data, it was estimated that there are currently 187,686 subjects with NVAF in
      Algeria. Seventy per cent of this population was treated for prevention, half of
      which were controlled. Cost of prevention was estimated at 203 million DZD (?1.5
      million) for drugs and 349 million DZD (?2.6 million) for examinations. Mean
      hospitalization costs for complications ranged between 123,500 and 435,500 DZD
      (?910-3,209), according to the type and severity of complications.
      Hospitalization costs for thromboembolic and hemorrhagic complications were
      estimated at 8,313 million DZD (?62 million), half of which was for untreated
      patients. Finally, the economic burden of NVAF was estimated at 8,865 million DZD
      (>?65 million) annually. CONCLUSION: The economic burden of NVAF is important in
      Algeria, largely driven by untreated and INR-uncontrolled patients. There is a
      lack of information on the Algerian healthcare system that could increase
      uncertainty around this assessment, but it clearly establishes the importance of
      NVAF as a public health concern.

PMID- 30238815
TI  - North American Congress of Clinical Toxicology (NACCT) Abstracts 2018.

PMID- 30238814
TI  - Estradiol vaginal inserts (4 ug and 10 ug) for treating moderate to severe vulvar
      and vaginal atrophy: a review of phase 3 safety, efficacy and pharmacokinetic
      data.
AB  - OBJECTIVE: To review safety, efficacy and pharmacokinetic (PK) data from the
      phase 3 REJOICE trial, which evaluated a 17beta-estradiol (E2) softgel vaginal
      insert approved in 2018 for moderate to severe dyspareunia associated with
      menopausal vulvar and vaginal atrophy (VVA). METHODS: REJOICE
      (Clinicaltrials.gov: NCT02253173) was a randomized, double-blind, placebo
      controlled trial in which women with moderate to severe dyspareunia due to
      menopausal VVA received 4 ug, 10 ug or 25 ug of an E2 vaginal insert or placebo
      for 12 weeks. The published data for the recently approved 4 ug and 10 ug doses
      of the E2 vaginal insert, including four co-primary efficacy endpoints (change
      from baseline to week 12 in percentages of superficial and parabasal cells,
      vaginal pH and severity of dyspareunia), safety and PK (which included serum E2
      levels measured by gas chromatography and tandem mass spectrometry), are
      summarized here. RESULTS: Women were randomized to receive the E2 vaginal insert
      (4 ug [n = 186] or 10 ug [n = 188]; Imvexxy a ) or placebo (n = 187) in the
      modified intention-to-treat population. The E2 vaginal insert (4 ug and 10 ug)
      significantly improved the percentages of superficial and parabasal cells (p <
      .0001), vaginal pH (p < .0001), and the severity score for dyspareunia (p < .05)
      from baseline to week 12 compared with placebo. The recently approved E2 vaginal
      insert was well tolerated, with no clinically significant differences in
      treatment-emergent or serious adverse events versus placebo. Systemic absorption
      of E2 with both doses was minimal. CONCLUSIONS: The recently FDA-approved E2
      softgel vaginal insert (4 ug and 10 ug) was safe and effective over 12 weeks for
      treating moderate to severe dyspareunia due to menopausal VVA with minimal
      systemic E2 levels.

PMID- 30238816
TI  - Heterodimeric BMP-2/7 exhibits different osteoinductive effects in human and
      murine cells.
AB  - As robust osteoinductive cytokines, bone morphogenetic proteins (BMPs) play a
      significant role in bone tissue engineering. Constituted of two different
      polypeptides, heterodimeric BMPs are more effective than the homodimers in bone
      formation. While most studies focused on the murine cell lines, such as murine
      preosteoblasts MC3T3-E1, the role of heterodimeric BMPs in the osteogenic
      differentiation of human cells remains uncertain, which hinders their application
      to practical treatment. In this study, we compared the osteoinductive effects of
      BMP-2/7 heterodimer in human adipose-derived stem cells (hASCs) with their
      homodimers BMP-2 and BMP-7, in which MC3T3-E1 cells were utilized as a positive
      control. The results indicated that BMP-2/7 was not a stronger inducer during the
      osteogenic differentiation of hASCs as that for MC3T3-E1, and extracellular
      signal-regulated kinase signaling played a role in the different effects of BMP
      2/7 between hASCs and MC3T3-E1. Our study demonstrates the osteoinductive effects
      of heterodimeric BMP-2/7 present in a cell-specific pattern and cautions should
      be taken when applying heterodimeric BMP-2/7 to clinical practice.

PMID- 30238817
TI  - A review on the treatment of sporadic inclusion body myositis with Bimagrumab and
      Alemtuzumab.
AB  - BACKGROUND: Sporadic inclusion body myositis is the most common inflammatory
      myopathy over the age of 50. The aetiopathogenesis of the disease remains unclear
      and to the day there is no effective treatment. OBJECTIVES: The aim of the
      present review is to present the latest data on the new insights and developments
      in the treatment of sporadic inclusion body myositis, focusing on Bimagrumab and
      Alemtuzumab. METHODS: For the purpose of the review we searched multiple internet
      databases in order to find the most recent studies and clinical trials on the
      safety, tolerability and efficacy of Bimagrumab and Alemtuzumab in sporadic
      inclusion body myositis. RESULTS: We found four trials on Bimagrumab, with one of
      them being an extension phase III study, and one small series trial on
      Alemtuzumab. The first clincopathological trial on Bimagrumab showed promising
      evidence, which were partially confirmed by the double-blinded controlled
      multicentre trial, however the primary endpoint of improving 6-m walking distance
      or improving the muscle strength has not been reached. The evidence from the
      Alemtuzumab trial was also promising, but the risk of bias of the study was
      relatively high, because it was open labelled, the number of patient was low and
      the yearly disease progression was much higher than in other recent studies.
      CONCLUSIONS: Although both Bimagrumab and Alemtuzumab were well tolerated and
      showed promising results, the Bimagrumab trial did not reach the primary
      endpoint, and the Alemtuzumab trial has a relatively high risk of bias and the
      results need to be interpreted with caution.

PMID- 30238818
TI  - Role of heme oxygenase-1 and its reaction product, carbon monoxide, in
      manifestation of breast cancer stem cell-like properties: Notch-1 as a putative
      target.
AB  - Cancer stem cells (CSCs) constitute a subpopulation of transformed cells that
      possess intrinsic ability to undergo selfrenewal and differentiation, which drive
      tumour resistance and cancer recurrence. It has been reported that CSCs possess
      enhanced protection against oxidative stress induced by reactive oxygen species
      compared with nonstem-like cancer cells. In the present work, we investigated the
      role of heme oxygenase-1 (HO-1), a representative antioxidant enzyme, on the
      stemness and selfrenewal of human breast CSCs. We found that pharmacologic or
      genetic inhibition of HO-1 attenuated the sphere formation, whereas HO-1 inducers
      enhanced the number and the size of tumourspheres in breast CSCs. Carbon monoxide
      (CO) is endogenously generated as a consequence of degradation of heme by HO-1.
      The proportion of populations of CD44+/CD24- cells retaining CSC properties was
      increased in MDA-MB-231 cells treated with a CO-releasing molecule (CORM-2).
      Following CORM-2 treatment, the expression of Notch-1 and related genes Jagged-1
      and Hes1 was increased, which was accompanied by the mammosphere formation. Taken
      together, these findings suggest that HO-1-derived CO production stimulates the
      formation of mammospheres in breast cancer cells through activation of Notch-1
      signalling.

PMID- 30238819
TI  - How far are we from vaccination against Helicobacter pylori infection?
AB  - INTRODUCTION: Helicobacter pylori infection results in chronic gastritis, peptic
      ulcer, or gastric cancer; therefore, eradication of this bacterium is essential.
      The strategy for developing effective vaccines against H. pylori entails
      immunization of mice with a combination of classical and recombinant H. pylori
      antigens, but this has proven to be onerous in all cases. Areas covered: We have
      reviewed literature databases in PubMed and Scopus using the key words H. pylori,
      vaccine, and vaccination and have conducted a systematic review of published
      clinical trials and animal model studies on vaccines against H. pylori and have
      tried to summarize why the vaccines are not effective or only partially
      effective. Expert commentary: This is the perfect time to review vaccine
      development against H. pylori as, after several failed attempts, promising
      results were reported by Zeng et al. in 2015. Successful vaccine development
      requires knowledge of both the immune mechanisms active during natural infection
      by H. pylori, owing to the complicated host response against the pathogen, and
      the factors that allow the persistence of bacteria, such as genetic diversity of
      H. pylori. Moreover, various clinical trials are needed to prove vaccine
      efficacy.

PMID- 30238820
TI  - Role of developmental venous anomalies in etiopathogenesis of demyelinating
      diseases.
AB  - OBJECTIVE: Multiple sclerosis (MS) is a demyelinating autoimmune disease of the
      central nervous system. T2W-hyperintense demyelinating lesions are detected in
      cranial magnetic resonance imaging (MRI). Developmental venous anomalies (DVAs)
      have frequently been detected in enhanced cranial MRI images, and are generally
      accepted as normal variants of venous development. The aim of the present study
      was to investigate whether there was an association between demyelinating
      diseases and venous anomalies. METHODS: One hundred five patients who were
      diagnosed as having MS in accordance with the McDonald diagnostic criteria, and
      105 patients who were diagnosed as having vascular headache who had no lesions
      similar to MS were included in the present retrospective study. RESULTS: DVAs
      were detected in 31 of the study group and in 14 patients in the control group. A
      statistically significant higher rate of DVAs and abnormal signal increase in the
      neighboring tissue was detected in the study group (p = 0.004) (p = 0.006). The
      DVA was superficially localized in the RRMS, It was deeply located in RIS.
      CONCLUSION: Recent studies have emphasized the association of the central vein
      and the lesion severity of MS with the detection of the central collecting vein
      in MS lesions. In our study, DVAs, which are generally regarded as innocent
      developmental anomalies, and neighboring signal increase were found significantly
      higher in the MS group compared with the control group. The role of DVAs in the
      etiology of demyelinating lesions must be clarified through comprehensive future
      studies that use more advanced techniques.

PMID- 30238821
TI  - New insights into the structure of PINK1 and the mechanism of ubiquitin
      phosphorylation.
AB  - Mutations in PINK1 cause early-onset recessive Parkinson's disease. This gene
      encodes a protein kinase implicated in mitochondrial quality control via
      ubiquitin phosphorylation and activation of the E3 ubiquitin ligase Parkin. Here,
      we review and analyze functional features emerging from recent crystallographic,
      nuclear magnetic resonance (NMR) and mass spectrometry studies of PINK1. We
      compare the apo and ubiquitin-bound PINK1 structures and reveal an allosteric
      switch, regulated by autophosphorylation, which modulates substrate recognition.
      We critically assess the conformational changes taking place in ubiquitin and the
      Parkin ubiquitin-like domain in relation to its binding to PINK1. Finally, we
      discuss the implications of these biophysical findings in our understanding of
      the role of PINK1 in mitochondrial function, and analyze the potential for
      structure-based drug design.

PMID- 30238822
TI  - A Nutrition Environment Measure to Assess Tribal Convenience Stores: The THRIVE
      Study.
AB  - In rural American Indian (AI) communities, where supermarkets are rare, tribally
      owned and operated convenience stores are an important food source. Food
      environment measures for these settings are needed to understand and address the
      significant diet-related disparities among AIs. Through a tribal-university
      partnership that included tribal health and commerce representatives from two
      Native Nations in rural southeastern Oklahoma, we developed the Nutrition
      Environment Measures Survey for Tribal Convenience Stores (NEMS-TCS) to inform
      the development and evaluation of a healthy food retail intervention. The NEMS
      TCS assessed four scored domains of the rural convenience store food environment
      food availability, pricing, quality, and placement-and included 11 food
      categories that emphasized ready-to-eat food items. Trained raters administered
      the NEMS-TCS using a sample of 18 rural convenience stores (primarily ranging
      between 2,400 and 3,600 square feet). We assessed interrater reliability with
      kappa statistics for dichotomized variables and intraclass correlation
      coefficients (ICC) for continuous variables. NEMS-TCS demonstrated high inter
      rater reliability for all food categories (>85% agreement), subscores (ICC = 0.73
      1.00), and the total score (ICC = 0.99). The NEMS-TCS responds to recent calls
      for reliable measures for rural food environments and may be valuable for
      studying food environments of large convenience stores in other Native Nations as
      well as other rural settings.

PMID- 30238823
TI  - Susceptibility-weighted imaging in post-treatment evaluation in the early stage
      in patients with acute ischemic stroke.
AB  - Objective This study aimed to investigate the association between abnormal signs
      on susceptibility-weighted imaging (SWI) and post-treatment outcome in the early
      stage in patients with acute ischemic stroke. Methods Thirty-seven patients with
      middle cerebral artery territory infarction were recruited. Baseline and 24-hour
      follow-up magnetic resonance imaging was performed. Pre- and 24-hour post
      treatment clinical conditions were assessed with the National Institutes of
      Health Stroke Scale (NIHSS) score. Prominent vessel sign (PVS) on SWI and
      infarcted areas on diffusion-weighted imaging (DWI) were assessed using the
      Alberta Stroke Program Early CT (ASPECT) score system. Susceptibility vessel sign
      (SVS) was evaluated and recorded. The associations between image abnormalities
      and clinical scores were analyzed. Results PVS was found in 35 patients and SVS
      in seven patients. The extent of PVS was significantly correlated with the post
      treatment DWI ASPECT score (r = 0.79), but not with the post-treatment NIHSS
      score or the post-pre NIHSS difference score. The presence of SVS was
      significantly correlated with the post-treatment NIHSS score (r = 0.41).
      Conclusion PVS might be a useful predictor of early imaging prognosis and infarct
      growth in patients with acute ischemic stroke. SVS is related to a poor early
      outcome and could be useful for assessing stroke.

PMID- 30238824
TI  - Use of artificial neural networks for analysis of the factors affecting particle
      size in mebudipine nanoemulsion.
AB  - In this study, a nanoemulsion containing mebudipine (composed of ethyl oleate
      (oil phase), Tween 80, Span 80 (surfactants), polyethylene glycol 400 and ethanol
      (cosurfactants) and deionized water) was prepared with the aim of improving its
      bioavailability for an effective antihypertensive therapy. Particle size of the
      formulation was measured by dynamic light scattering. Then, artificial neural
      networks (ANNs) was used in identifying factors that influence the particle size
      of the nanoemulsion. Three variables, namely, amount of surfactant system (Tween
      80 +Span 80), amount of polyethylene glycol and amount of ethanol as
      cosurfactants, were considered as input values and the particle size was used as
      output. The developed model showed that all the three inputs had some degrees of
      effect on particles size: Increasing the value of each input decreased the size.
      Furthermore, amount of surfactant was found to be the dominant factor in
      controlling the final particle size of nanoemulsion.

PMID- 30238825
TI  - Making stars physical: the astronomy of Sir John Herschel.

PMID- 30238826
TI  - Victim Crossover Index Offending Patterns and Predictors in a Portuguese Sample.
AB  - Sex offenders who cross over in victims' age, gender and relationship usually
      have a greater number of victims, which is associated with sexual recidivism.
      This investigation aimed to examine the prevalence of crossover index offending
      in Portugal, and to explore the predictive ability of sociodemographic and
      criminological variables on this outcome. A retrospective sample of 247 male
      individuals incarcerated for sex offenses in a Portuguese prison was drawn from
      official records. From those offenders with multiple victims ( n = 94), 48% had
      victims of different age categories, 10% had both gendered victims, and 12% had
      intrafamilial and extrafamilial victims. Comparative statistics and logistic
      regressions were able to identify variables that distinguished noncrossover and
      crossover offenders and that predicted crossover, respectively. While likely
      underestimates of the prevalence of victim crossover, these findings are compared
      to previous international studies and provide a better understanding of the
      phenomenon.

PMID- 30238827
TI  - G-quadruplex-forming oligodeoxyribonucleotides activate leukotriene synthesis in
      human neutrophils.
AB  - Human polymorphonuclear leukocytes (PMNLs, neutrophils) play a major role in the
      immune response to bacterial and fungal infections and eliminate pathogens
      through phagocytosis. During phagocytosis of microorganisms, the 5-lipoxygenase
      (5-LOX) pathway is activated resulting in generation of leukotrienes, which
      mediate host defense. In this study, a library of oligodeoxyribonucleotides
      (ODNs) with varying numbers of human telomeric repeats (d(TTAGGG)n) and their
      analogues with phosphorothioate internucleotide linkages and single-nucleotide
      substitutions was designed. These ODNs with the potential to fold into G
      quadruplex structures were studied from structural and functional perspectives.
      We showed that exogenous G-quadruplex-forming ODNs significantly enhanced 5-LOX
      metabolite formation in human neutrophils exposed to Salmonella Typhimurium
      bacteria. However, the activation of leukotriene synthesis was completely lost
      when G-quadruplex formation was prevented by substitution of guanosine with 7
      deazaguanosine or adenosine residues at several positions. To our knowledge, this
      study is the first to demonstrate that G-quadruplex structures are potent
      regulators of 5-LOX product synthesis in human neutrophils in the presence of
      targets of phagocytosis.

PMID- 30238828
TI  - Eye-tracking evidence for active gap-filling regardless of dependency length.
AB  - Previous work on real-time sentence processing has established that comprehenders
      build and interpret filler-gap dependencies without waiting for unambiguous
      evidence about the actual location of the gap ("active gap-filling") as long as
      such dependencies are grammatically licensed. However, this generalisation was
      called into question by recent findings in a self-paced reading experiment by
      Wagers and Phillips, which may be taken to show that comprehenders do not
      interpret the filler at the posited gap when the dependency spans a longer
      distance. In the present study, we aimed to replicate these findings in an eye
      tracking experiment with better controlled materials and increased statistical
      power. Crucially, we found clear evidence for active gap-filling across all
      levels of dependency length. This diverges from Wagers and Phillips's findings
      but is in line with the long-standing generalisation that comprehenders build and
      interpret filler-gap dependencies predictively as long as they are grammatically
      licensed. We found that the effect became smaller in the long dependency
      conditions in the post-critical region, which suggests the weaker effect in the
      long dependency conditions may have been undetected in Wagers and Phillips's
      study due to insufficient statistical power and/or the use of a self-paced
      reading paradigm.

PMID- 30238829
TI  - A combination of bioactive and nonbioactive alkyl-peptides form a more stable
      nanofiber structure for differentiating neural stem cells: A molecular dynamics
      simulation survey.
AB  - Self-assembling alkyl-peptides are important molecules due to their ability to
      construct nano-level structures such as nanofibers to be utilized as tissue
      engineering scaffolds. The bioactive epitope of FAQRVPP which acts as neural stem
      cells (NSCs) outgrowth inducing factor is used in nanofiber structures. Based on
      previous experimental studies the density and distribution pattern of the
      epitopes on the surface of the nanofibers plays an important role in the
      differentiation function efficiency. We decided to survey and compare the
      stability of two pre-constructed fiber structures in the forms of all
      functionalized nanofiber (containing only bioactive alkyl-peptides) and
      distributed functionalized nanofiber (a combination of nonbioactive and bioactive
      alkyl-peptides with ratio 2:1). Our findings reveal that the all-functionalized
      fiber shows an unstable structure and is split into intermediate micelle-like
      structures to reduce compactness and steric hindrance of functional epitopes
      whereas the distributed functionalized fiber shows an integrated stable nanofiber
      with a more amount of beta sheets that are well-organized and oriented around the
      hydrophobic core. The hydrogen bonds and energy profiles of the structures
      indicate the role of hydrophobic interactions during the alkyl-chain core
      formation and the important role of electrostatic interactions and hydrogen bond
      network in the stability of the final structures. Finally, it seems that the
      possibility of the presence of intermediate structure is increased in the all
      functionalized nanofiber environment, and it can reduce function efficiency of
      the scaffolds. These findings can help to design more efficient nanofiber
      structures with different goals in scaffolds for tissue engineering.

PMID- 30238830
TI  - 'We can act different from what we used to': Findings from experiences of
      religious leader participants in an HIV-prevention intervention in Zambia.
AB  - Faith-based organisations (FBOs) have long been part of the fight against HIV and
      AIDS. International bodies continue to collaborate with FBOs to implement HIV
      prevention programmes with mixed success. Zambia has been a target of such
      programmes in part due to its high HIV prevalence. The Trusted Messenger approach
      to provide religious leader networks with biomedical, science-focused education
      about HIV and AIDS was piloted in 2006, but participant experiences of the
      intervention have not been explored qualitatively. In 2016, in-depth interviews
      were conducted of 34 randomly chosen individuals who attended Trusted Messenger
      workshops between 2006 and 2016 in Livingstone, Lusaka, and the Copperbelt
      region. Findings indicate that the religious leader attendees gained scientific
      insights about HIV which motivated their action in personal, social, and
      religious contexts. Participants found the science comprehensible and empowering
      and identified workshop frequency and language as challenging. Utilising science
      focused education within contextual settings of religious leader networks can
      combat the spread of HIV and the mistreatment of people living with HIV and AIDS.

PMID- 30238831
TI  - Comparing length and frequency effects in children across modalities.
AB  - Although it is well established that beginning readers rely heavily on
      phonological decoding, the overlap of the phonological pathways used in visual
      and auditory word recognition is not clear. Especially in transparent languages,
      phonological reading could use the same pathways as spoken word processing. In
      the present study, we report a direct comparison of lexical decision performance
      in the visual and auditory modality in beginning readers of a transparent
      language. Using lexical decision, we examine how marker effects of length and
      frequency differ in the two modalities and how these differences are modulated by
      reading ability. The results show that both frequency and length effects are
      stronger in the visual modality, and the differences in length effects between
      modalities are more pronounced for poorer readers than for better readers. This
      suggests that visual word recognition in beginning readers of a transparent
      language initially is based on phonological decoding and subsequent matching in
      the phonological lexicon, especially for poor readers. However, some orthographic
      processing seems to be involved already. We claim that the relative contribution
      of the phonological and orthographic route in beginning readers can be measured
      by the differences in marker effects between auditory and visual lexical
      decision.

PMID- 30238832
TI  - Mechanistic Insights into High Mobility Group Box-1 (HMGb1) induced Toll-like
      Receptor 4 (TLR4) Dimer Formation.
AB  - High mobility group box-1 (HMGb1), an endogenous danger-associated molecular
      pattern protein (DAMP) whose extracellular release has been associated with
      sterile injury and various inflammatory diseases and conditions, has been shown
      to be a valuable clinical drug target. Elucidation of the specific interactions
      with the HMGb1 receptor, toll-like receptor 4 (TLR4) and adaptor protein myeloid
      differentiation factor-2 (MD-2), will lead to more precisely targeted
      therapeutics. We sought to examine detailed interactions and dynamics of the
      HMGb1 A-box and B-box fragments, as well as the intact protein using in silico
      protein-protein docking (Zdock, Zrank) and molecular dynamics (Schrodinger
      Desmond). Mutagenesis and SPR binding studies allowed us to draw further
      conclusions regarding the details of the HMGb1-TLR4-MD2 interaction and shed
      light on the reasons for the opposing biological activities of HMGb1 A-box and B
      box fragments. From our findings we hypothesize that disulfide A-box fragment
      binds as an anchor toward the TLR4-MD-2 but does not facilitate the TLR4 dimer
      formation, thereby competing with the HMGb1 binding site and preventing HMGb1
      induced signalling and downstream inflammation. Whereas the pro-inflammatory B
      box fragment retains the MD-2 active conformation and binds to both TLR4 proteins
      in the complex to aid TLR4 dimer formation, which activates the intracellular
      signalling for downstream inflammatory pathways and cytokine release.

PMID- 30238833
TI  - Actionable vascular and other incidental findings on CTA in patients undergoing
      acute stroke intervention.
AB  - Providing a fast and accurate diagnosis of acute large-vessel occlusion on
      computed tomography angiograms (CTAs) is essential for timely intervention and
      good stroke outcomes. However, the detection and appropriate management of
      incidental findings are also important parts of any clinical radiology practice
      and can greatly affect patient care. The intricate anatomy covered by CTAs of the
      head and neck coupled with the time pressures of acute stroke diagnosis creates
      an environment in which unrelated, important findings can potentially be missed.
      The purpose of our study was to document clinically actionable incidental
      findings on CTA in 225 patients undergoing acute stroke intervention. After
      institutional review board approval, a retrospective six-year review of CTAs of
      the head and neck in patients undergoing acute stroke intervention was performed
      for actionable incidental vascular and nonvascular findings. A total of 225
      patients undergoing acute stroke intervention with documented intracranial large
      vessel occlusion on CTAs were consecutively enrolled in the study. Incidental
      vascular findings were identified in 17 of 225 patients (7.5%, 95% confidence
      interval 5% to 12%). Previously unreported aneurysms ranging from 2 mm to 10 mm
      in size represented 18 of 19 vascular findings in these patients. Incidental
      nonvascular findings were identified in 32 patients (14%, 95% confidence interval
      5% to 12%). These included malpositioned support lines and tubes; pneumothorax;
      interstitial lung disease; newly diagnosed metastatic disease; nasopharyngeal,
      parotid, and pituitary masses; and cervical spine compression fractures. CTAs of
      the head and neck in patients undergoing acute stroke intervention contain a
      relatively high frequency of vascular and nonvascular incidental findings
      requiring further follow-up, and therefore should be evaluated carefully and
      systematically.

PMID- 30238834
TI  - Family Dynamics and Young Adults' Well-Being: The Mediating Role of Sibling
      Bullying.
AB  - Although a common form of family violence, sibling bullying is often viewed as
      harmless by families and society. Consequently, it has not received as much
      attention in research compared with peer bullying or other types of family
      violence, such as interpartner violence, child abuse, and elder abuse.
      Considering that sibling relationships have lasting effects on children's
      development, this retrospective study focused on the antecedents and outcomes of
      sibling bullying. Grounded in family system theory and social learning theory, it
      explored whether sibling bullying during childhood and adolescence mediated the
      relationship between negative family dynamics (i.e., sibling rivalry,
      interparental hostility, and parental hostility) and young adults' well-being
      (i.e., sense of competence, internalized problems, self-esteem, and satisfaction
      with life). Data from 216 respondents were analyzed using structural equation
      modeling. Results revealed that young adults who reported higher levels of
      sibling rivalry and interparental hostility were more likely to be victims of
      sibling bullying. In turn, sibling bullying was associated with lower sense of
      competence, self-esteem, and life satisfaction, as well as more internalized
      problems. Parents' hostile behaviors toward their children were not associated
      with sibling bullying but were negatively associated with well-being in early
      adulthood. Our work underlines the importance of harmonious family dynamics and
      the need for sibling bullying to be taken more seriously by parents and family
      members. From a clinical point of view, our findings suggest that clinicians and
      human service workers should adopt a family-level approach when trying to reduce
      sibling bullying and its negative outcomes by educating parents about the
      interdependence of family relationships.

PMID- 30238835
TI  - Diagnostic and prognostic value of HE4 in female patients with primary peritoneal
      carcinoma.
AB  - BACKGROUND: HE4 is a useful tumor marker for the diagnosis of ovarian,
      endometrial, and fallopian tube carcinoma. AIM: The aim of our study was to
      investigate the value of serum HE4 compared with CA125 in the diagnosis of
      primary peritoneal carcinoma and the estimation of treatment response and
      recurrence. METHODS: Serum HE4 and CA125 concentrations were measured in both
      primary peritoneal carcinoma patients and benign gynecological disease controls.
      The treatment response and recurrence were assessed by serum HE4 and CA125 levels
      in primary peritoneal carcinoma patients. RESULTS: Serum HE4 and CA125 levels
      were significantly increased in primary peritoneal carcinoma patients compared
      with benign disease controls ( P<0.001). Compared with CA125, HE4 had lower
      sensitivity (84.2% vs. 94.7%), but higher specificity (99.2% vs. 85.3%); the
      combination of HE4 and CA125 led to higher sensitivity and specificity. In the
      receiver operating characteristic analysis, the area under the curve was 0.956
      for HE4, for CA125 was 0.953, for HE4+CA125 was 0.979. Furthermore, HE4 and CA125
      were closely associated with treatment response, and our results indicated that
      primary peritoneal carcinoma patients displayed a larger drop of HE4 compared
      with CA125 (75.8% vs. 61.5%). Combined with CA125, HE4 elevation better predicted
      recurrence in primary peritoneal carcinoma patients during the remission period
      after treatment. CONCLUSIONS: This study indicated that the detection of serum
      HE4 changes may enhance the effectiveness for detecting primary peritoneal
      carcinoma and estimating the outcome of treatment and recurrence in female
      primary peritoneal carcinoma patients.

PMID- 30238836
TI  - The validity of the commercially-available, low-cost, wrist-worn Movband
      accelerometer during treadmill exercise and free-living physical activity.
AB  - Low-cost physical activity monitors may provide a more accurate measure of
      physical activity than subjective methods (e.g., self-report) while being less
      costly than research-grade accelerometers. The present study assessed the
      validity of a low-cost monitor (Movband 2) to estimate physical activity
      behavior/intensity. Participants (N = 23, n = 16 female, BMI = 22.9 +/- 4.0
      kg/m2, age = 21.9 +/- 1.6 years) completed four, five-minute treadmill stages
      (2.0, 3.0, 4.0, 5.0 MPH) while wearing both the Movband and the previously
      validated Actigraph monitor. Oxygen consumption (VO2) was recorded during each
      stage (Laboratory assessment). A subset (n = 15, n = 10 female, BMI = 22.2 +/-
      3.2 kg/m2, age = 21.5 +/- 0.8 years) of these participants then wore the two
      accelerometers for three days (Free-living assessment). During the Laboratory
      assessment there were strong, significant (r = 0.94, p <= 0.001) relationships
      between Movband and Actigraph counts and VO2. During Free-living assessment there
      was also a strong, significant (r = 0.97, p < 0.001) correlation between Movband
      and Actigraph counts. The low-cost, Movband accelerometer appears to provide a
      valid assessment of physical activity behavior/intensity.

PMID- 30238837
TI  - Relationship between GSTP1 rs1695 gene polymorphism and myelosuppression induced
      by platinum-based drugs: a meta-analysis.
AB  - Although many previous studies have reported the relationship between GSTP1
      rs1695 gene polymorphism and myelosuppression induced by platinum-based drugs,
      the conclusions are not consistent. The aim of the study is to evaluate the
      association between granulocytopenia and thrombocytopenia induced by platinum
      based drugs and GSTP1 rs1695 gene polymorphism by meta-analysis. A literature
      search was performed using the Pubmed, Embase, CNKI, and Wanfang databases, and
      the odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate
      the correlation. Finally,12 case-control studies comprising 1657 patients were
      included in our study. GSTP1 rs1695 gene polymorphism showed a significant
      correlation with granulocytopenia induced by platinum-based drugs (dominant
      genetic model: OR=1.60, 95% CI=1.19. 2.15, P=0.002; recessive genetic model:
      OR=3.72, 95% CI=1.73, 8.00, P=0.001; allelic genetic model: OR=1.76, 95% CI=1.34,
      2.33, P=0.001). This gene polymorphism is not associated with thrombocytopenia
      (OR=0.87, 95% CI=0.47, 1.60, P=0.649). False-positive report probability showed
      that the association between polymorphism and adverse reactions is true.
      Sensitivity analysis showed that the results were stable. However, there was a
      certain publication bias in the included studies. In conclusion, the GSTP1 rs1695
      gene polymorphism is associated with granulocytopenia induced by platinum-based
      drugs.

PMID- 30238838
TI  - Critical appraisal of commercially available suspending vehicles for
      extemporaneous compounding of cardiovascular medicines: physical and chemical
      stability mini review.
AB  - Oral liquid formulations are compounded by pharmacists to meet the needs of
      patients when a suitable commercially available product is not available. To
      minimise the errors associated with measuring multiple excipients and to enhance
      the shelf-life of the medicines, commercially available suspending bases are
      commonly used. This review aims to compare the stability and shelf life of
      commercially available extemporaneous formulation to traditional formulation
      methods. Five (5) databases were searched (Pubmed, SCOPUS, Science direct, Embase
      and EBSCOhost). Twelve articles, comprising of seven cardiovascular medications
      (amiodarone, captopril, carvedilol, furosemide, nifedipine, sotalol and
      valsartan), met the study inclusion criteria and were reviewed. Chemical
      stability of the drugs was comparable between the two formulation methods except
      for furosemide, captopril and valsartan. The traditional compounding method
      provided superior stability for furosemide (90 days vs 14 days) and captopril (50
      days vs 14 days), while the commercial vehicles provided superior stability for
      valsartan (90 days vs 14 days). Physical stability tests indicated that
      sedimentation does occur with both formulation methods. Microbial studies within
      the data were lacking and further research can be undertaken in this area. This
      review highlights the importance of assessing the suitability of compounding
      ingredients prior to preparation of the formulation.

PMID- 30238839
TI  - Attempting to Restore Integrity of the Self: A Grounded Theory Study of Recovery
      From Major Depressive Disorder.
AB  - BACKGROUND: The cultural and social background of the individual would seem to be
      important factors that can affect recovery from major depressive disorder (MDD).
      Currently, there is little information on the process of recovery from MDD in
      Middle Eastern countries, such as Iran. AIMS: This study was conducted to explore
      the process of recovery from MDD in Iran. METHOD: A grounded theory approach by
      Corbin and Strauss was used to explore recovery from MDD. Twenty patients were
      recruited using purposive and theoretical sampling methods. RESULTS: Several
      themes emerged from the data, the primary of which was "Attempting to restore
      integrity of the self," which included the two subthemes of "Attempting to
      restore health," and "Attempting to reacquire the lost abilities." Various
      contextual factors also affected recovery, including poverty, inefficient health
      care systems, perceived support, feelings of failure, and social stigma. During
      the recovery process, participants adopted both "effective strategies" and
      "ineffective strategies." Following the attempt to restore integrity,
      participants experienced different levels of integrity, ranging from "complete
      recovery" to "no recovery/relapse." CONCLUSIONS: The results from this study
      contribute to the body of knowledge regarding recovery from MDD in Iran. The data
      suggest that recovery from depressive disorder is a very personal experience that
      is affected by different and variable factors and conditions. However, the
      attempt to restore integrity of the self can result in achieving a higher level
      of performance and health.

PMID- 30238840
TI  - Modulation of rat synaptosomal ATPases and acetylcholinesterase activities
      induced by chronic exposure to the static magnetic field.
AB  - PURPOSE: It is considered that exposure to static magnetic fields (SMF) may have
      both detrimental and therapeutic effect, but the mechanism of SMF influence on
      the living organisms is not well understood. Since the adenosine triphosphatases
      (ATPases) and acetylcholinesterase (AChE) are involved in both physiological and
      pathological processes, the modulation of Na+/K+-ATPase, ecto-ATPases and AChE
      activities, as well as oxidative stress responses were followed in synaptosomes
      isolated from rats after chronic exposure toward differently oriented SMF.
      MATERIAL AND METHODS: Wistar albino rats were randomly divided into three
      experimental groups (six animals per group): Up and Down group - exposed to
      upward and downward oriented SMF, respectively, and Control group. After 50 days,
      the rats were sacrificed, and synaptosomes were isolated from the whole rat brain
      and used for testing the enzyme activities and oxidative stress parameters.
      RESULTS: Chronic exposure to 1 mT SMF significantly increased ATPases, AChE
      activities, and malondialdehyde (MDA) level in both exposed groups, compared to
      control values. The significant decrease in synaptosomal catalase activity (1.48
      +/- 0.17 U/mg protein) induced by exposure to the downward oriented field,
      compared to those obtained for Control group (2.60 +/- 0.29 U/mg protein), and Up
      group (2.72 +/- 0.21 U/mg protein). CONCLUSIONS: It could be concluded that
      chronic exposure to differently oriented SMF increases ATPases and AChE
      activities in rat synaptosomes. Since brain ATPases and AChE have important roles
      in the pathogenesis of several neurological diseases, SMF influence on the
      activity of these enzymes may have potential therapeutic importance.

PMID- 30238841
TI  - Clinical significance of fucosylated GP73 in the differential diagnosis of
      hepatocellular carcinoma.
AB  - OBJECTIVE:: To investigate the clinical value of fucosylated GP73 (Fuc-GP73)
      levels for differential diagnosis of hepatocellular carcinoma from other liver
      diseases. METHODS:: Serum specimens were collected from 50 patients with
      hepatocellular carcinoma, 60 patients with other digestive system diseases
      (ODSD), and 40 normal controls. Lectin affinity chromatography column combining
      with the enzyme-linked immunosorbent assay (ELISA) using the ELISA index was
      utilized to measure the level of Fuc-GP73. By receiver operating characteristic
      (ROC) curve analysis its sensitivity and specificity were used to evaluate the
      diagnostic significance of Fuc-GP73 in hepatocellular carcinoma. RESULTS:: The
      median serum Fuc-GP73 level of hepatocellular carcinoma (20.4 MUg/L) was much
      higher than that of ODSD patients (1.8 MUg/L) and the normal controls group (0.3
      MUg/L), significantly ( P <0.01). There was no significant correlation between
      serum Fuc-GP73 level and sex, age, and tumor size in the hepatocellular carcinoma
      group ( P > 0.05); however, it was related to tumor, node, metastasis stage and
      lymph node metastasis ( P <0.05). The area under the ROC curve (AUC) of Fuc-GP73
      to detect hepatocellular carcinoma alone was 0.885; with the prespecified
      specificity of 95%, the sensitivity and the cutoff value were 82% and 3.1 MUg/L.
      In addition, the combined test of Fuc-GP73 with other biomarkers can improve the
      clinical diagnostic efficiency; the AUC can reach to 0.983; and with the
      prespecified specificity of 95% its sensitivity increased to 94%. CONCLUSION::
      Fuc-GP73 can act as a superior glycobiomarker for the differential diagnosis of
      hepatocellular carcinoma; its combined detection with other biomarkers can
      improve diagnostic accuracy.

PMID- 30238842
TI  - Recurrent DNA damage is associated with persistent injury in progressive
      radiation-induced pulmonary fibrosis.
AB  - PURPOSE: Radiation-induced lung injuries (RILI), namely radiation pneumonitis
      and/or fibrosis, are dose-limiting outcomes following treatment for thoracic
      cancers. As part of a search for mitigation targets, we sought to determine if
      persistent DNA damage is a characteristic of this progressive injury. METHODS:
      C57BL/6J female mice were sacrificed at 24 h, 1, 4, 12, 16, 24 and 32 weeks
      following a single dose of 12.5 Gy thorax only gamma radiation; their lungs were
      compared to age-matched unirradiated animals. Tissues were examined for DNA
      double-strand breaks (DSBs) (gamma-H2A.X and p53bp1), cellular senescence
      (senescence-associated beta-galactosidase and p21) and oxidative stress
      (malondialdehyde). RESULTS: Data revealed consistently higher numbers of DSBs
      compared to age-matched controls, with increases in gamma-H2A.X positivity beyond
      24 h post-exposure, particularly during the pathological phases, suggesting
      periods of recurrent DNA damage. Additional intermittent increases in both
      cellular senescence and oxidative stress also appeared to coincide with
      pneumonitis and fibrosis. CONCLUSIONS: These novel, long-term data indicate (a)
      increased and persistent levels of DSBs, oxidative stress and cellular senescence
      may serve as bioindicators of RILI, and (b) prevention of genotoxicity, via
      mitigation of free radical production, continues to be a potential strategy for
      the prevention of pulmonary radiation injury.

PMID- 30238843
TI  - Dental Care Utilization and Service Needs Among American Indian/Alaska
      Native/Native Hawaiian Elders: 2008 to 2017.
AB  - OBJECTIVE: This study describes trends in self-reported dental care utilization
      and services needed among American Indian/Alaska Native/Native Hawaiian
      (AI/AN/NH) elders 2008 to 2017, including demographic and socioeconomic
      variability. METHOD: Researchers utilized data from the Survey of Elders
      administered by the National Resource Center on Native American Aging,
      representing all regions of the United States and 262 tribes. Data were analyzed
      comparing means over time and between/within groups. RESULTS: Between April 2008
      and March 2017, there was a statistically significant ( p < .001) increase in the
      proportion of older adults who visited a dentist and an increase in need for
      treatment. A smaller proportion of older adults reported need for treatment among
      those who were privately insured, high income, had no tobacco use, were employed,
      and had visited a dental professional in the last year. DISCUSSION: These
      findings highlight current dental needs among tribal elders while also
      identifying elders at greater risk of poor oral health.

PMID- 30238844
TI  - A nuclear membrane-derived structure associated with Atg8 is involved in the
      sequestration of selective cargo, the Cvt complex, during autophagosome formation
      in yeast.
AB  - : Macroautophagy (hereafter autophagy) is a conserved intracellular degradation
      mechanism required for cell survival. A double-membrane structure, the
      phagophore, is generated to sequester cytosolic cargos destined for degradation
      in the vacuole. The mechanism involved in the biogenesis of the phagophore is
      still an open question. We focused on 4 autophagy-related (Atg) proteins (Atg2,
      Atg9, Atg14, and Atg18), which are involved in the formation of the phagophore in
      order to gain a more complete understanding of the membrane dynamics that occur
      during formation of the autophagosome. The corresponding mutants, while defective
      in autophagy, nonetheless generate the membrane-bound form of Atg8, allowing us
      to use this protein as a marker for the nascent autophagosome precursor membrane.
      Using electron microscopy (EM), we discovered in these atg mutants a novel single
      membrane structure (~120 to 150 nm in size). Electron tomography revealed that
      this structure originates from a part of the nuclear membrane, and we have named
      it the alphasome. Our data suggest that the alphasome is associated with Atg8,
      and sequesters selective cargo, the Cvt complex, during autophagy. ABBREVIATIONS:
      3D: three-dimensional; AB: autophagic body; AP: autophagosome; Atg: autophagy
      related; Cvt: cytoplasm-to-vacuole targeting; EM: electron microscopy; IEM:
      immunoelectron microscopy; L: lipid droplet; N: nucleus; NM: nuclear membrane;
      PAS: phagophore assembly site; PE: phosphatidylethanolamine; prApe1: precursor
      aminopeptidase I; rER: rough endoplasmic reticulum; TEM: transmission electron
      microscopy; V: vacuole; VLP: virus-like particle.

PMID- 30238845
TI  - The Association Between PTSD Symptoms and IPV Perpetration Across 6 Years.
AB  - A large literature documents that posttraumatic stress disorder (PTSD) symptoms
      are associated with intimate partner violence (IPV) perpetration among adults.
      However, research on this relationship among adolescents and young adults has
      been plagued by methodological flaws (e.g., cross-sectional designs). Thus, the
      purpose of the present study was to examine the longitudinal and bidirectional
      associations between PTSD symptoms and psychological and physical IPV
      perpetration from adolesence to young adulthood. A sample of racially and
      ethnically diverse high school students ( N = 1,042; 56% female) were assessed
      annually for 6 years (from 2010 to 2015 in Southeastern Texas). At each
      assessment, participants completed measures of PTSD symptoms and psychological
      and physical IPV perpetration. The mean age of the sample at the first assessment
      was 15.09 ( SD = .79). Structural equation modeling demonstrated that PTSD
      symptoms at Years 2, 3, and 4 predicted increases in psychological IPV
      perpetration in the subsequent year. In turn, psychological IPV perpetration at
      Years 1 and 4 predicted increases in PTSD symptoms in the subsequent years. In
      addition, psychological IPV perpetration mediated the association between PTSD
      symptoms and physical IPV perpetration over time. Results were consistent across
      gender and race/ethnicity. Findings provide initial evidence that PTSD symptoms
      are associated with IPV perpetration across time from adolescence to young
      adulthood. Prevention and intervention programs for adolescent and young adult
      IPV perpetration may benefit from screening for, and potentially treating, PTSD
      symptoms.

PMID- 30238846
TI  - Contribution of allosteric disulfide in the structural regulation of membrane
      bound tissue factor-factor VIIa binary complex.
AB  - Two distinct populations, active and cryptic forms of tissue factor (TF), reside
      on the cell surface. Apart from phospholipid contribution, various models have
      been introduced to explain decryption/encryption of TF. The proposed model, the
      switching of Cys186-Cys209 bond of TF, has become the matter of controversy.
      However, it is well accepted that this disulfide has an immense influence upon
      ligand factor VIIa (FVIIa) for its binding. However, molecular level
      understanding for this remains unveiled due to lack of detailed structural
      information. In this regard, we have performed the molecular dynamic study of
      membrane-bound TF/TF-FVIIa in both the forms (+/-Cys186-Cys209 allosteric
      disulfide bond), individually. Dynamic study depicts that disulfide bond provides
      structural rigidity of TF in both free and ligand-bound forms. This disulfide
      bond also governs the conformation of FVIIa structure as well as the binding
      affinity of FVIIa toward TF. Significant differences in lipid-protein interaction
      profiles of both the forms of TF in the complex were observed. Two forms of TF,
      oxidized and reduced, have different structural conformation and behave
      differentially toward its ligand FVIIa. This disulfide bond not only alters the
      conformation of GLA domain of FVIIa in the vicinity but allosterically regulates
      the conformation of the distantly located FVIIa protease domain. We suggest that
      the redox status of the disulfide bond also governs the lipid-mediated
      interactions with both TF and FVIIa. Communicated by Ramaswamy H. Sarma.

PMID- 30238847
TI  - Design of antimalarial transmission blocking agents: Pharmacophore mapping of
      ligands active against stage-V mature gametocytes of Plasmodium falciparum.
AB  - The discovery of transmission-blocking (T-B) agents is crucial for preventing and
      complete removal of malaria infection. However, most of the existing
      antimalarials are only active against the asexual stages of Plasmodium parasite,
      but ineffective against the sexual stage (gametocytes). In this background, we
      have developed pharmacophore models against the stage-V mature gametocytes of P.
      falciparum parasites. The pharmacophore model (Hypo-1) showed five pharmacophoric
      features namely, one hydrogen bond donor (HBD), one hydrophobic aliphatic (HYAl),
      one ring aromatic (RA), and two hydrophobic aromatic (HYAr) essential for the
      anti-gametocytic activity. The amino, methyl, fused phenyl ring of the
      quinazoline heterocycle, two phenyl rings of biphenyl moiety (HBD, HYAl, HYAr1,
      HYAr2 and RA) are the crucial features responsible for the non-specific anti
      gametocytic activity (PfG). Subsequently, the model (Hypo-2) developed against
      the stage-V female gametocytes (PffG) showed the contribution of three
      pharmacophoric features namely, two hydrogen bond acceptor (HYA) and one RA
      required for the anti-gametocytic activity. The sulfhydryl, imine and pyridyl
      groups are observed to be essential for anti-gametocytic activity against female
      gametocytes. Both the models (PfG and PfGG) showed the classification accuracies
      of 78.26 and 71.64% for training set compounds and 60.80 and 60.18% for the test
      set compounds, respectively, for classification of compounds into higher and
      lower active classes. Also, both the models were found to retain the higher
      active compounds (IC50 <100 nM) in top 1% of total compounds (actives and decoys)
      as observed after screening the decoy set compounds. Communicated by Ramaswamy H
      Sarma.

PMID- 30238848
TI  - Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and
      migration of human tumor cells.
AB  - : In a tumor microenvironment, endothelial cell migration and angiogenesis allow
      cancer to spread to other organs causing metastasis.  Indeed, a number of
      molecules that are involved in cytoskeleton re-organization and intracellular
      signaling have been investigated for their effects on tumor cell growth and
      metastasis. Alongside that, Amblyomin-X, a recombinant Kunitz-type protein, has
      been shown to reduce metastasis and tumor growth in in vivo experiments. In the
      present report, we provide a mechanistic insight to these antitumor effects, this
      is,  Amblyomin-X modulates Rho-GTPases and uPAR signaling, and reduces the
      release of MMPs, leading to disruption of the actin cytoskeleton and decreased
      cell migration of tumor cell lines. Altogether, our data support a role for
      Amblyomin-X as a novel potential antitumor drug. ABBREVIATIONS: Amb-X: Amblyomin
      X; ECGF: endotelial cell growth factor; ECM: extracellular matrix; GAPDH:
      glyceraldehyde-3-phosphate dehydrogenase; HUVEC: human umbilical vein endothelial
      cell; LRP1: low-density lipoprotein receptor-related protein; MMP: matrix
      metalloproteinase; HPI-4: hedgehog pathway inhibitor 4; PAI-1: plasminogen
      activator inhibitor 1; PMA: phorbol 12-myristate-13-acetate; TFPI: tissue factor
      pathway inhibitor; uPA: urokinase plasminogen activator; uPAR: uPA receptor.

PMID- 30238849
TI  - Posterior Percutaneous Endoscopic Cervical Discectomy Through Lamina-hole
      Approach for Cervical Intervertebral Disc Herniation.
AB  - : of Background Data. The optimal PECD surgical approach for CIVDH remains
      controversial.?The conventional posterior K-hole approach for PECD leads to
      damage of facet joint. OBJECTIVES: This paper is to first describe a novel
      posterior lamina-hole approach of percutaneous endoscopic cervical discectomy for
      cervical intervertebral disc herniation(CIVDH). To evaluate the feasibility and
      short-term clinical effect of this approach. METHODS: Single-center retrospective
      observational study of all patients managed with PPECD using the lamina-hole
      approach for symptomatic single-level CIVDH between January 2015 and January
      2016. The clinical outcomes were evaluated with the visual analog scale, modified
      MacNab criteria, and radiographical results. RESULTS: 12 patients (7 women, 5
      men) were enrolled in the study. Positive clinical response for pain relief was
      achieved in these patients receiving posterior percutaneous endoscopic cervical
      discectomy through lamina-hole approach for cervical intervertebral disc
      herniation. Postoperative MRI showed complete removal of the disc material in all
      the patients, no failure due to residual fragment was observed. CONCLUSION: As an
      alternative surgical approach of PPECD, PPECD through lamina-hole approach is a
      novel access for CIVDH and may be considered a valid and safe therapeutic option
      for cervical intervertebral disc herniation. The advantages of this approach are
      not only providing a valid and secure access to herniated cervical intervertebral
      fragment but also avoiding the iatrogenic damage to the facet joint and relevant
      functional spinal unit (FSU). Theoretically, the potential of secondary
      degeneration of FSU is low.

PMID- 30238850
TI  - A cancer associated somatic mutation in LC3B attenuates its binding to E1-like
      ATG7 protein and subsequent lipidation.
AB  - Macroautophagy/autophagy is a conserved catabolic process that maintains cellular
      homeostasis under basal growth and stress conditions. In cancer, autophagy can
      either prevent or promote tumor growth, at early or advanced stages,
      respectively. We screened public databases to identify autophagy-related somatic
      mutations in cancer, using a computational approach to identify cancer mutational
      target sites, employing exact statistics. The top significant hit was a missense
      mutation (Y113C) in the MAP1LC3B/LC3B (microtubule associated protein 1 light
      chain 3 beta) protein, which occurred at a significant frequency in cancer, and
      was detected in early stages in primary tumors of patients with known tumor
      lineage. The mutation reduced the formation of GFP-LC3B puncta and attenuated
      LC3B lipidation during Torin1-induced autophagy. Its effect on the direct
      physical interaction of LC3B with each of the 4 proteins that control its
      maturation or lipidation was tested by applying a protein-fragment
      complementation assay and co-immunoprecipitation experiments. Interactions with
      ATG4A and ATG4B proteases were reduced, yet without perturbing the cleavage of
      mutant LC3B. Most importantly, the mutation significantly reduced the interaction
      with the E1-like enzyme ATG7, but not the direct interaction with the E2-like
      enzyme ATG3, suggesting a selective perturbation in the binding of LC3B to some
      of its partner proteins. Structure analysis and molecular dynamics simulations of
      LC3B protein and its mutant suggest that the mutation changes the conformation of
      a loop that has several contact sites with ATG4B and the ATG7 homodimer. We
      suggest that this loss-of-function mutation, which attenuates autophagy, may
      promote early stages of cancer development.

PMID- 30238851
TI  - Investigation of selective binding of inhibitors to PTP1B and TCPTP by
      accelerated molecular dynamics simulations.
AB  - Protein tyrosine phosphatase 1B (PTP1B), a key negative regulator in insulin
      signaling pathways, is regarded as a potential target for the treatment of type
      II diabetes and obesity. However, the mechanism underlying the selectivity of
      PTP1B inhibitors against T-cell protein tyrosine phosphatase (TCPTP) remains
      controversial, which is due to the high similarity between PTP1B and TCPTP
      sequence and the fact that no ligand-protein complex of TCPTP has been
      established yet. Here, the accelerated molecular dynamics (aMD) method was used
      to investigate the structural dynamics of PTP1B and TCPTP that are bound by two
      chemically similar inhibitors with distinct selectivity. The conformational
      transitions during the "open" to "close" states of four complexes were captured,
      and free energy profiles of important residue pairs were analyzed in detail.
      Additional MM-PBSA calculations confirmed that the binding free energies of final
      states were consistent with the experimental results, and the energetic
      contributions of important residues were further investigated by alanine scanning
      mutagenesis. By comparing the four complexes, the different conformational
      behavior of WPD-loop, R-loop, and the second pTyr binding site induced by
      inhibitors were featured and found to be crucial for the selectivity of
      inhibitors. This study provides new mechanistic insights of specific binding of
      inhibitors to PTP1B and TCPTP, which can be exploited to the further structural
      based inhibitor design. Communicated by Ramaswamy H. Sarma.

PMID- 30238852
TI  - Centers for Medicare & Medicaid Services' decision on drug-coated balloons: No
      additional reimbursement despite higher cost and highest levels of scientific
      evidence.

PMID- 30238853
TI  - Multispectroscopic studies of the interaction of folic acid with glycated human
      serum albumin.
AB  - The interaction between glycated human serum albumin (gHSA) and folic acid (FA)
      was investigated by various spectroscopic techniques, such as fluorescence,
      circular dichroism, UV-vis absorption spectroscopy and electrophoretic light
      scattering technique. These methods characterize the binding properties of an
      albumin-folic acid system. The binding constants values (Ka) at 300 and 310 K are
      about 104 M-1. The standard enthalpy change (DeltaH) and the standard entropy
      change (DeltaS) were calculated to be ~-20 kJ mol-1 and ~16 J mol-1 K-1,
      respectively, which indicate characteristic electrostatic interactions between
      gHSA and folic acid. The CD studies showed that there are no significant
      conformational changes in the secondary structure of the protein. Moreover, the
      zeta potential measurements proved that under physiological conditions the gHSA
      folic acid complex shows instability. No significant changes in the secondary
      structure of the protein and reversible drug binding are the desirable effect
      from pharmacological point of view. Communicated by Ramaswamy H. Sarma.

PMID- 30238854
TI  - Service Provider Difficulties in Operationalizing Coercive Control.
AB  - We examined perspectives of social workers, police officers, and specialist
      domestic abuse practitioners about their perceived ability and organizational
      readiness to respond effectively to incidents of coercive and controlling
      behavior. Interviews revealed intervention and risk assessment strategies
      structured around an outdated, maladaptive concept of domestic abuse as an
      unambiguous and violent event and frontline services that lacked appreciation of
      the power dynamics inherent in controlling relationships. The analysis
      demonstrates how lack of definitional clarity around nonphysical domestic abuse
      can increase the use of discretion by frontline services and, by extension,
      increase the discounting of coercive control by pressured frontline officers.

PMID- 30238855
TI  - Primary intestinal aspergillosis resulting in acute intestinal volvulus after
      autologous stem cell transplantation in a patient with relapsed non-Hodgkin
      lymphoma: report on a rare infectious complication and a review of the
      literature.
AB  - OBJECTIVES: Since primary intestinal aspergillosis is a severe infectious
      complication with a high morbidity and mortality in immunocompromised patients,
      we want to draw attention to this rare entity and the importance of early
      recognition. METHODS: We report a case of documented primary intestinal
      aspergillosis in a patient receiving an autologous stem cell transplantation
      (SCT). Furthermore, this article gives a short reflection on the occurrence of
      invasive aspergillosis in autologous SCT and the value of serum galactomannan
      levels based on literature search and linked with the case. RESULTS: In this case
      the patient presented on day +8 after autologous SCT for a relapsed diffuse large
      B-cell lymphoma with an acute abdomen with urgent need for surgical intervention.
      Biopsy revealed the presence of fungal colonies due to aspergillosis and
      voriconazole was started. Until that day the systematically taken serum
      galactomannan tests were all negative or pending. Initially there was some
      resistance to perform surgery in the presence of neutropenia and thrombocytopenia
      but in the end it provided the definitive diagnosis and should not be delayed.
      Until now this patient is in good health and retains a complete remission.
      CONCLUSION: With this case, we would like to emphasize that early recognition of
      primary intestinal aspergillosis is of the utmost importance as it is a rare but
      serious infectious complication. It should be included in the differential
      diagnosis of neutropenic patients with sudden onset abdominal pain and ongoing
      fever, even in the absence of a positive serum galactomannan.

PMID- 30238856
TI  - Tips from Former Smokers: A Content Analysis of Persuasive Message Features.
AB  - Years of research on message design and effects provides insight regarding the
      most persuasive message appeals. The purpose of this study was to evaluate the
      content of the messages being presented in the Centers for Disease Control and
      Prevention's Tips from Former Smokers campaign. A content analysis of persuasive
      message design features was conducted to critically examine campaign content.
      Campaign materials were coded for the presence of message variables including
      emotional appeals, evidence presentation, message framing, attitude functions,
      and source characteristics. Four independent coders analyzed 122 campaign
      messages, including video, print, and social media posts. Results from this
      content analysis indicate that the campaign contained more fear and guilt
      appeals, than other emotions. Evidence was typically presented in the form of a
      narrative from sources with firsthand experience. Suggestions for persuasive
      message design in large-scale public health communication campaigns are
      discussed.

PMID- 30238857
TI  - Balancing Industry and Drug Policy Objectives in the Pharmaceutical Sector: The
      Case of China.
AB  - Objectives This article assessed the balance between industry and drug policy
      objectives in the pharmaceutical sector in China. Methods The articles were
      mainly identified through databases such as Elsevier, Google Scholar, and
      SpringerLink, among others. Related articles were mainly separated into three
      categories: studies on drug policies, studies related to China's new health-care
      reform policy, and studies concerning patent policies. Results A relatively
      healthy environment for continuous innovation and drug patent protection in the
      pharmaceutical industry has been created in China, and the public's drug benefits
      have also significantly improved. However, the balance between industrial and
      drug policy objectives in the pharmaceutical sector in China requires additional
      attention. Discussion and conclusions The results suggest that the government
      should pay more attention to incentivizing enterprises' innovation, but the
      current Essential Medicines System in China has limited innovation. Hence, the
      mechanism for selecting essential medicines should be reformed, and certain
      appropriate and reasonably innovative medicines should be included. Additionally,
      medicine coverage, especially the coverage of essential drugs for primary care
      should be expanded to improve public health benefits. Furthermore, the
      pharmaceutical industry should be incorporated into the prospective National Drug
      Policy to achieve a balance between public benefits and pharmaceutical industry
      development in the future.

PMID- 30238858
TI  - Qualitative Evaluation of the Jump2HealthTM Website for Parents of Preschool
      Children Shows Behavior Changes.
AB  - Few interventions have been shown to be successful in reducing child obesity, due
      in part to the challenges in reaching parents. Web-based nutrition intervention
      is becoming more feasible due to technology advancements and accessibility across
      income groups. However, studies on the effectiveness and acceptability of web
      based interventions to teach parents about healthy behaviors are needed. The
      purpose of this study was to evaluate the Jump2HealthTM Website intervention
      using qualitative interview methodology. A follow-up phone interview was
      conducted with 13 participants, approximately 1-to 2-month-postintervention.
      Participants reported making desired behavior changes in targeted areas and also
      considered the Website an effective learning method.

PMID- 30238859
TI  - Why do some participants in colorectal cancer screening choose not to undergo
      colonoscopy following a positive test result? A qualitative study.
AB  - OBJECTIVE: Our aim was to investigate why participants opted out of colonoscopy
      following a positive screening result for colorectal cancer. DESIGN: Semi
      structured, qualitative, single interviews. We audio-recorded and transcribed all
      interviews verbatim and used Strauss and Corbin's concept of open, axial, and
      selective coding to identify the main categories shared across all interviews.
      These formed the basis of our findings. SETTING: A Danish national colorectal
      cancer screening programme. SUBJECTS: Single interviews with 13 participants who
      declined to have a colonoscopy. MAIN OUTCOME MEASURES: Reasons to decline
      colonoscopy after positive screening test. RESULTS: Participants gave 42
      different reasons for deciding not to have a colonoscopy and we coded them into
      nine main categories; Practical barriers, Discomfort of the examination, Personal
      integrity, Multimorbidity, Feeling healthy, Not having the energy, Belief that
      cancer is not present, Risk of complications, and Distrust in the accuracy of the
      iFOBT. CONCLUSIONS: Our findings suggest that some practical barriers could be
      quite easily addressed, by offering the participants alternative management and
      procdures. IMPLICATIONS: Further research is needed to examine how widely our
      findings are represented in the general population, and how general practitioners
      should consult with patients who have opted out of colonoscopy, despite a
      positive screening result. Key points   Some screening participants are reluctant
      to proceed with further diagnostic tests for colorectal cancer following a
      positive screening result.   * Interviews with people, who had refused a follow
      up colonoscopy, discovered nine categories (42 reasons) of reasons for refusal.  
      * Reluctance can be addressed by offering support with pre-procedure preparations
      and alternatives to colonoscopy.   * General practitioners face ethical dilemmas
      and challenges, when patients at risk of colorectal cancer decline to proceed
      with screening.

PMID- 30238860
TI  - Active listing and more consultations in primary care are associated with shorter
      mean hospitalisation and interacting with psychiatric disorders when adjusting
      for multimorbidity, age and sex.
AB  - OBJECTIVE: Patient-provider relationships with primary care and need for
      hospitalisations are related within the complex networks comprising healthcare.
      Our objective was to analyse mean days hospitalised, using registration status
      (active or passive listing) with a provider and number of consultations as
      proxies of patient-provider relationships with primary care, adjusting for
      morbidity burden, age and sex while analysing the contribution of psychiatric
      disorders. The Johns Hopkins Adjusted Clinical Groups Case-Mix System was used to
      classify morbidity burden into Resource Utilization Band (RUB) 0-5. DESIGN: Cross
      sectional population study using zero-inflated negative binomial regression.
      SETTING AND SUBJECTS: All population in the Swedish County of Blekinge (N = 151
      731) in 2007. MAIN OUTCOME MEASURE: Mean days hospitalised. RESULTS: Actively
      listed were in mean hospitalised for 0.86 (95%CI 0.81-0.92) and passively listed
      for 1.23 (95%CI 1.09-1.37) days. For 0-1 consultation mean days hospitalised was
      1.16 (95%CI 1.08-1.23) and for 4-5 consultations 0.68 (95%CI 0.62-0.75) days. At
      RUB3, actively listed were in mean hospitalised for 3.45 (95%CI 2.84-4.07) days
      if diagnosed with any psychiatric disorder and 1.64 (95%CI 1.50-1.77) days if
      not. Passively listed at RUB3 were in mean hospitalised for 5.17 (95%CI 4.36
      5.98) days if diagnosed with any psychiatric disorder and 2.41 (95%CI 2.22-2.60)
      days if not. CONCLUSIONS: Active listing and more consultations were associated
      with a decrease in mean days hospitalised, especially for patients with
      psychiatric diagnoses. IMPLICATIONS: Promoting good relationships with primary
      care could be an opportunity to decrease mean days hospitalised, especially for
      patients with more complex diagnostic patterns. Key Points Primary care
      performance, patient-provider relationships and need for hospitalisation are
      related within the complex networks comprising healthcare systems. Good patient
      provider relationships, i.e. more consultations and active listing, with primary
      care are associated with decreasing mean days hospitalised. The impact of patient
      provider relationships in primary care on mean days hospitalised increased when
      psychiatric disorders added to patient complexity.

PMID- 30238861
TI  - Effect of the support systems' compliance on total hip modular taper seating
      stability.
AB  - Assembly of a femoral head onto the stem remains non-standardized. The literature
      shows altering mechanical conditions during seating affects taper strength and
      lower assembly load may increase fretting corrosion during cyclic tests. This
      suggests overall performance may be affected by head assembly method. The purpose
      of this test was to perform bench-top studies to determine influence of peak
      force magnitude, load rate, and compliance of the system's support structure on
      initial stability of the taper. Custom manufactured CoCrMo femoral heads and Ti
      6Al-4V taper analog samples were assembled with varying peak force magnitudes (2
      10.1 kN), load rates (quasi-static vs impaction), and system compliance (rigid vs
      compliant). A clinically-relevant system compliance design was based off of force
      data collected during a cadaver impaction study. Tensile loads were then applied
      to disassemble the taper and quantify initial taper stability. Results indicated
      that taper stability (assessed by disassembly forces) increased linearly with
      assembly force and load rate did not have a significant effect on taper
      stability. When considering system compliance, a 42%-50% larger input energy,
      dependent on assembly force, was required in the compliant group to achieve a
      comparable impaction force to the rigid group. Even when this impaction force was
      achieved, the correlation between the coefficient, defined as distraction force
      divided by assembly load, was significantly reduced for the compliant test group.
      The compliant setup was intended to simulate a surgical scenario where patient
      and surgical factors may influence the resulting compliance. Based on results,
      surgical procedure and patient variables may have a significant effect on initial
      taper stability.

PMID- 30238863
TI  - "Salia de uno y me meti en otro 1 ": Exploring the Migration-Violence Nexus Among
      Central American Women.
AB  - Increasing numbers of Central American women cross the U.S.-Mexico border,
      prompting social service providers, advocates, and policy makers to investigate
      motivations and appropriate responses. Drawing from a constructivist grounded
      theory study and in-depth qualitative interviews, this article explores women's
      experiences of domestic and sexual violence in relation to migration. Findings
      reveal interconnections across multiple and interconnecting categories of
      violence as precipitating factors for migration, during border-crossing, and
      following arrival in the United States. This study fills gaps in our
      understanding of the violence-migration nexus and provides direction for policy,
      practice, and advocacy, in the context of shifting political landscapes and
      migration trends.

PMID- 30238862
TI  - Multi-objective integrated planning and scheduling model for operating rooms
      under uncertainty.
AB  - This article formulates the operating rooms considering several constraints of
      the real world, such as decision-making styles, multiple stages for surgeries,
      time windows for resources, and specialty and complexity of surgery. Based on
      planning, surgeries are assigned to the working days. Then, the scheduling part
      determines the sequence of surgeries per day. Moreover, an integrated fuzzy
      possibilistic-stochastic mathematical programming approach is applied to consider
      some sources of uncertainty, simultaneously. Net revenues of operating rooms are
      maximized through the first objective function. Minimizing a decision-making
      style inconsistency among human resources and maximizing utilization of operating
      rooms are considered as the second and third objectives, respectively. Two
      popular multi-objective meta-heuristic algorithms including Non-dominated Sorting
      Genetic Algorithm and Multi-Objective Particle Swarm Optimization are utilized
      for solving the developed model. Moreover, different comparison metrics are
      applied to compare the two proposed meta-heuristics. Several test problems based
      on the data obtained from a public hospital located in Iran are used to display
      the performance of the model. According to the results, Non-dominated Sorting
      Genetic Algorithm-II outperforms the Multi-Objective Particle Swarm Optimization
      algorithm in most of the utilized metrics. Moreover, the results indicate that
      our proposed model is more effective and efficient to schedule and plan surgeries
      and assign resources than manual scheduling.

PMID- 30238864
TI  - Are Whites and minorities more similar than different? Testing the cultural
      similarities hypothesis on psychopathology with a second-order meta-analysis.
AB  - The cultural differences hypothesis is the assertion that there are large
      differences between Whites and racial/ethnic minorities in the United States,
      while there are small differences between- (e.g., African Americans and Latinos)
      and within- (e.g., Latinos: Mexican Americans and Cuban Americans) minority
      groups. Conversely, the cultural similarities hypothesis argues that there are
      small differences between Whites and minorities, and these differences are equal
      or smaller in magnitude than differences between and within minorities. In this
      study, we conducted a second-order meta-analysis focused on psychopathology, to
      (a) test these hypotheses by estimating the absolute average difference between
      Whites and minorities, as well as between and within minorities, on levels of
      psychopathology, and (b) determine if general and meta-analytic method moderators
      account for these differences. A systematic search in PsycINFO, Web of Science,
      and ProQuest Dissertations identified 16 meta-analyses (13% unpublished) on 493
      primary studies (N = 3,036,749). Differences between Whites and minorities (d+ =
      0.23, 95% confidence interval [0.18, 0.28]), and between minorities (d+ = 0.30,
      95% confidence interval [0.12, 0.48]) were small in magnitude. White-minority
      differences remained small across moderators. These findings support the cultural
      similarities hypothesis. We discuss their implications and future research
      directions.

PMID- 30238865
TI  - A cultural neuroscience perspective on North Korean strategic culture.
AB  - Given the complexity of the current nuclear age and the absence of work on
      deterrence under true multipolarity, interdisciplinary models can provide new
      perspectives on tailored deterrence. Drawing from recent findings in the life
      sciences, this article offers a cultural neuroscience approach to deterrence
      decision-making, with special attention given to the ways in which culture
      interacts with cognition and the security environment to shape behavioral
      outcomes during conflict. Since North Korea remains largely a "black box" in
      international relations, a cultural neuroscience perspective can provide valuable
      insight into the effects of cultural conditioning on perception and cognition
      within the context of nuclear deterrence on the Korean Peninsula. Through an
      analysis of the bureaucratic and military structures, leadership characteristics,
      and institutional landscapes shaping North Korean strategic culture, this article
      examines the influences of historical memory and cultural values, such as
      collectivism, honor, and face-saving, on political decision-making in Pyongyang.

PMID- 30238866
TI  - Symptom prevalence and management in older adult patients in Lebanon.
AB  - OBJECTIVE: The purpose of this study is to explore symptoms and the effectiveness
      of their management in older adult palliative care candidates in Lebanon. The
      aims of this study were to: (1) determine symptom prevalence in Lebanese older
      adults who qualify for palliative care; (2) identify the severity and distress of
      symptoms; (3) identify the prevalence of symptom management and its efficacy; and
      (4) explore the relationship between overall symptom burden and its correlates.
      METHOD: This study uses an observational cross-sectional design using convenience
      sampling (N = 203) to recruit older adults qualifying for palliative care from
      three major medical centers in Lebanon.ResultThe mean age of the sample was 78.61
      years. The most prevalent symptoms were lack of energy (93.5%), worrying (83.2%),
      and pain (71.4%). Psychological symptoms had the highest mean scores, preceded
      only by the physical symptoms and lack of energy. The most treated symptoms were
      physical with pain having the highest treatment prevalence (91%). Although
      psychological symptoms were the most burdensome, they were poorly treated.
      Multiple regression analysis showed that symptom scores had significant positive
      associations with financial status, social functioning, and comorbidities; there
      was a negative association with age.Significance of resultsLack of energy and
      psychological symptoms were the most prevalent, with the latter having the
      highest mean total symptom scores. Treatment was poor for psychological symptoms
      and effective for physical ones. Associations were found between age,
      comorbidity, financial problems, social functioning, and total physical and
      psychological mean symptom burden scores. More attention needs to be given to
      psychological symptoms and their management among older adults receiving
      palliative care.

PMID- 30238867
TI  - Disaster Risk Reduction in Schools: The Relationship of Knowledge and Attitudes
      Towards Preparedness from Elementary School Students in School-Based Disaster
      Preparedness in the Mentawai Islands, Indonesia.
AB  - : IntroductionLocated in the Sunda Megathrust zone, Mentawai Island is known as
      the epicenter of an active earthquake that has the potential to cause a tsunami.
      Students would be one of the most vulnerable groups during the
      disaster.ProblemThe low-level of School-Based Disaster Preparedness/Sekolah Siaga
      Bencana (SSB) of students' preparedness in disaster risk reduction (DRR) can lead
      to increased vulnerability of students in facing disaster threats, especially a
      tsunami. METHODS: The study employed observational, correlative analytics with a
      cross-sectional approach. The sample includes 109 students from fifth and sixth
      grade in three elementary schools in Sipora, Mentawai Island district. RESULTS:
      There was a significant influence between knowledge and attitude towards the
      preparedness of SSB students in DRR in Sipora, Mentawai Islands district.
      CONCLUSIONS: Knowledge and attitudes are key factors that must be taken into
      account in efforts to increase student preparedness to reduce the risk of a
      tsunami disaster.Sujarwo, Noorhamdani, Fathoni M. Disaster risk reduction in
      schools: the relationship of knowledge and attitudes towards preparedness from
      elementary school students in school-based disaster preparedness in the Mentawai
      Islands, Indonesia.

PMID- 30238868
TI  - A mixed methods analysis of perceived cognitive impairment in hematopoietic stem
      cell transplant survivors.
AB  - OBJECTIVE: Hematopoietic stem cell transplant (HSCT) survivors may show evidence
      of objective cognitive impairment; however, perceived cognitive problems and
      their impact on quality of life are less well-understood. The purpose of this
      study was to explore HSCT survivors' perceptions of cognitive impairment and its
      effect on daily life functioning. METHOD: Sixty-nine autologous and allogeneic
      HSCT survivors nine months to three years posttransplant experiencing mild
      survivorship problems completed a brief structured interview regarding perceived
      cognitive impairment since transplant. Data were coded and content analyzed. The
      frequency of participants reporting cognitive problems by domain and associations
      between reports of cognitive problems and age, depressed mood, anxiety, and
      health-related quality of life were examined.ResultOverall, 49 of the 69
      participants (71%) reported cognitive impairments after transplant: 38 in memory
      (55%), 29 in attention and concentration (42%), and smaller numbers in other
      domains. There were no significant differences in problems reported by transplant
      type. Of the 50 participants who worked before transplant, 19 (38%) did not
      return to work following transplant, with 12 citing cognitive and health problems
      as being the reason. There were significant associations between reports of
      cognitive impairment and younger age (p = 0.02), depressed mood (p = 0.02),
      anxiety (p = 0.002), and health-related quality of life (p = 0.008).Significance
      of resultsA large proportion of survivors reported cognitive impairment following
      HSCT that impaired daily life functioning. Perceived cognitive impairment was
      associated with younger age, greater distress and reduced health-related quality
      of life.

PMID- 30238869
TI  - Enterotoxic Clostridia: Clostridium perfringens Enteric Diseases.
AB  - In humans and livestock, Clostridium perfringens is an important cause of
      intestinal infections that manifest as enteritis, enterocolitis, or
      enterotoxemia. This virulence is largely related to the toxin-producing ability
      of C. perfringens. This article primarily focuses on the C. perfringens type F
      strains that cause a very common type of human food poisoning and many cases of
      nonfoodborne human gastrointestinal diseases. The enteric virulence of type F
      strains is dependent on their ability to produce C. perfringens enterotoxin
      (CPE). CPE has a unique amino acid sequence but belongs structurally to the
      aerolysin pore-forming toxin family. The action of CPE begins with binding of the
      toxin to claudin receptors, followed by oligomerization of the bound toxin into a
      prepore on the host membrane surface. Each CPE molecule in the prepore then
      extends a beta-hairpin to form, collectively, a beta-barrel membrane pore that
      kills cells by increasing calcium influx. The cpe gene is typically encoded on
      the chromosome of type F food poisoning strains but is encoded by conjugative
      plasmids in nonfoodborne human gastrointestinal disease type F strains. During
      disease, CPE is produced when C. perfringens sporulates in the intestines. Beyond
      type F strains, C. perfringens type C strains producing beta-toxin and type A
      strains producing a toxin named CPILE or BEC have been associated with human
      intestinal infections. C. perfringens is also an important cause of enteritis,
      enterocolitis, and enterotoxemia in livestock and poultry due to intestinal
      growth and toxin production.

PMID- 30238871
TI  - The sound of drums: Severe acute kidney injury following a Djembe session.

PMID- 30238870
TI  - Restricted fluid bolus versus current practice in children with septic shock: the
      FiSh feasibility study and pilot RCT.
AB  - BACKGROUND: There has been no randomised controlled trial (RCT) of fluid bolus
      therapy in paediatric sepsis in the developed world despite evidence that excess
      fluid may be associated with harm. OBJECTIVES: To determine the feasibility of
      the Fluids in Shock (FiSh) trial - a RCT comparing restricted fluid bolus (10
      ml/kg) with current practice (20 ml/kg) in children with septic shock in the UK.
      DESIGN: (1) Qualitative feasibility study exploring parents' views about the
      pilot RCT. (2) Pilot RCT over a 9-month period, including integrated parental and
      staff perspectives study. SETTING: (1) Recruitment took place across four NHS
      hospitals in England and on social media. (2) Recruitment took place across 13
      NHS hospitals in England. PARTICIPANTS: (1) Parents of children admitted to a UK
      hospital with presumed septic shock in the previous 3 years. (2) Children
      presenting to an emergency department with clinical suspicion of infection and
      shock after 20 ml/kg of fluid. Exclusion criteria were receipt of > 20 ml/kg of
      fluid, conditions requiring fluid restriction and the patient not for full active
      treatment (i.e. palliative care plan in place). Site staff and parents of
      children in the pilot were recruited to the perspectives study. INTERVENTIONS:
      (1) None. (2) Children were randomly allocated (1 : 1) to 10- or 20-ml/kg fluid
      boluses every 15 minutes for 4 hours if in shock. MAIN OUTCOME MEASURES: (1)
      Acceptability of FiSh trial, proposed consent model and potential outcome
      measures. (2) Outcomes were based on progression criteria, including recruitment
      and retention rates, protocol adherence and separation between the groups, and
      collection and distribution of potential outcome measures. RESULTS: (1) Twenty
      one parents were interviewed. All would have consented for the pilot study. (2)
      Seventy-five children were randomised, 40 to the 10-ml/kg fluid bolus group and
      35 to the 20-ml/kg fluid bolus group. Two children were withdrawn. Although the
      anticipated recruitment rate was achieved, there was variability across the
      sites. Fifty-nine per cent of children in the 10-ml/kg fluid bolus group and 74%
      in the 20-ml/kg fluid bolus group required only a single trial bolus before shock
      resolved. The volume of fluid (in ml/kg) was 35% lower in the first hour and 44%
      lower over the 4-hour period in the 10-ml/kg fluid bolus group. Fluid boluses
      were delivered per protocol (volume and timing) for 79% of participants in the 10
      ml/kg fluid bolus group and for 55% in the 20-ml/kg fluid bolus group, mainly as
      a result of delivery not being completed within 15 minutes. There were no deaths.
      Length of hospital stay, paediatric intensive care unit (PICU) transfers, and
      days alive and PICU free did not differ significantly between the groups. Two
      adverse events were reported in each group. A questionnaire was completed by 45
      parents, 20 families and seven staff were interviewed and 20 staff participated
      in focus groups. Although a minority of site staff lacked equipoise in favour of
      more restricted boluses, all supported the trial. CONCLUSIONS: Even though a
      successful feasibility and pilot RCT were conducted, participants were not as
      unwell as expected. A larger trial is not feasible in its current design in the
      UK. FUTURE WORK: Further observational work is required to determine the
      epidemiology of severe childhood infection in the UK in the postvaccine era.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN15244462. 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. 22, No. 51. See the NIHR Journals Library website for
      further project information.

PMID- 30238874
TI  - Health in the European region: time to act on the evidence.

PMID- 30238875
TI  - Mismanaged expectations-maternal morbidity in the USA.

PMID- 30238876
TI  - Patient letters: improving an outdated system.

PMID- 30238872
TI  - Concerted IL-25R and IL-4Ralpha signaling drive innate type 2 effector immunity
      for optimal helminth expulsion.
AB  - Interleukin 25 (IL-25) is a major 'alarmin' cytokine, capable of initiating and
      amplifying the type immune response to helminth parasites. However, its role in
      the later effector phase of clearing chronic infection remains unclear. The
      helminth Heligmosomoides polygyrus establishes long-term infections in
      susceptible C57BL/6 mice, but is slowly expelled in BALB/c mice from day 14
      onwards. We noted that IL-25R (Il17rb)-deficient BALB/c mice were unable to expel
      parasites despite type 2 immune activation comparable to the wild-type. We then
      established that in C57BL/6 mice, IL-25 adminstered late in infection (days 14
      17) drove immunity. Moreover, when IL-25 and IL-4 were delivered to Rag1
      deficient mice, the combination resulted in near complete expulsion of the
      parasite, even following administration of an anti-CD90 antibody to deplete
      innate lymphoid cells (ILCs). Hence, effective anti-helminth immunity during
      chronic infection requires an innate effector cell population that is
      synergistically activated by the combination of IL-4Ralpha and IL-25R signaling.

PMID- 30238877
TI  - When no guideline recommendation is the best recommendation.

PMID- 30238878
TI  - Funds cut for aid in the occupied Palestinian territory.

PMID- 30238879
TI  - Crisis in the Chad Basin.

PMID- 30238880
TI  - Cochrane review methods called into question.

PMID- 30238881
TI  - Longevity in elite athletes: the first 4-min milers.

PMID- 30238882
TI  - It is time for universal HPV vaccination.

PMID- 30238883
TI  - Datafication of medical device use for training and device design.

PMID- 30238884
TI  - The future of end-of-life care.

PMID- 30238885
TI  - Coeliac disease and dermatitis herpetiformis.

PMID- 30238886
TI  - Coeliac disease and dermatitis herpetiformis.

PMID- 30238887
TI  - Health of Hungarians: worsens or improves?

PMID- 30238888
TI  - Coeliac disease and dermatitis herpetiformis - Authors' reply.

PMID- 30238889
TI  - What must be the role of INSERM in French biomedical research?

PMID- 30238890
TI  - Aortic calcification in longstanding, undiagnosed Takayasu arteritis.

PMID- 30238891
TI  - Melanoma.
AB  - Cutaneous melanoma causes 55 500 deaths annually. The incidence and mortality
      rates of the disease differ widely across the globe depending on access to early
      detection and primary care. Once melanoma has spread, this type of cancer rapidly
      becomes life-threatening. For more than 40 years, few treatment options were
      available, and clinical trials during that time were all unsuccessful. Over the
      past 10 years, increased biological understanding and access to innovative
      therapeutic substances have transformed advanced melanoma into a new oncological
      model for treating solid cancers. Treatments that target B-Raf proto-oncogene
      serine/threonine-kinase (BRAF)V600 (Val600) mutations using selected BRAF
      inhibitors combined with mitogen-activated protein kinase inhibitors have
      significantly improved response and overall survival. Furthermore, advanced
      cutaneous melanoma has developed into a prototype for testing checkpoint
      modulating agents, which has increased hope for long-term tumour containment and
      a potential cure. These expectations have been sustained by clinical success with
      targeted agents and antibodies that block programmed cell-death protein 1 in
      locoregional disease, which induces prolongation of relapse-free, distant
      metastasis-free, and overall survival times.

PMID- 30238893
TI  - Defining the Place of Adjuvant Chemotherapy and Radiation for High-Risk
      Endometrial Cancer From Recent Randomized Clinical Trials: Some Answers, More
      Questions.

PMID- 30238892
TI  - A Longitudinal Investigation of Associations Between Marijuana Displays on
      Facebook and Self-Reported Behaviors Among College Students.
AB  - PURPOSE: College students frequently display references to substance use,
      including marijuana, on social media such as Facebook. The significance of
      displayed marijuana references on social media is unknown. The purpose of this
      longitudinal cohort study was to evaluate college students' displayed
      marijuanareferences on Facebook and their association with self-reported
      marijuana use. METHODS: First-year students from two U.S. universities were
      randomly selected from registrar lists for recruitment. Data collection included
      4years of monthly Facebook coding, and yearly phone interviews that each assessed
      lifetime and current marijuana use. We compared frequencies of displayed
      marijuana references on Facebook between marijuana users and nonusers using two
      sample t-tests and Pearson's chi-squared tests. Generalized linear models were
      used to evaluate the likelihood of displayed marijuana references on Facebook.
      RESULTS: A total of 338 participants were recruited, 56.1% were female, 74.8%
      were Caucasian, and 58.8% were from the Midwest college. Prevalence of displayed
      marijuana references on Facebook profiles variedfrom 5% to 10% across 4 years.
      Displayed marijuana references included most "Actions" and "Locations" on the
      Facebook profile. Marijuana users were more likely to display marijuana
      references on Facebook compared to nonusers, though Likes were more common among
      nonusers. Predictors of displayed marijuana references included lifetime and
      current marijuana use. CONCLUSIONS: The prevalence of displayed marijuana
      references on Facebook was consistent but uncommon; marijuana references included
      both information sharing and personal experiences. Marijuana users were more
      likely to display marijuana references, suggesting these displays could be
      leveraged for intervention efforts.

PMID- 30238894
TI  - Implementing Radiation Therapy in Haiti: Current Status and Future Directions.

PMID- 30238895
TI  - Professor Gerrit Willem (Eddie) Barendsen, August 14, 1927 - June 20, 2018.

PMID- 30238896
TI  - A 63-Year-Old Woman With a Pineal Mass.

PMID- 30238897
TI  - Resection Bed Only.

PMID- 30238898
TI  - Not to Treat.

PMID- 30238899
TI  - The Higher the Grade, the Bigger the Field.

PMID- 30238900
TI  - Lymphoblastic Lymphoma: Guidelines From the International Lymphoma Radiation
      Oncology Group (ILROG).
AB  - Presentation with a large mediastinal mass is a hallmark of acute lymphoblastic
      lymphoma, a disease that is treated in the same way as acute lymphoblastic
      leukemia even in the absence of marrow involvement. The role of mediastinal
      radiation for patients who achieve complete remission after chemotherapy has been
      overlooked and controversial. This document presents current knowledge on the
      role of radiation for lymphoblastic lymphoma and best practices for addressing
      how to deliver mediastinal radiation with modern technology.

PMID- 30238901
TI  - Evidence-based Risk Stratification to Guide Hormone Therapy Use With Salvage
      Radiation Therapy for Prostate Cancer.

PMID- 30238902
TI  - In Regard to Bossi et al.

PMID- 30238903
TI  - In Reply to Fakhry et al.

PMID- 30238904
TI  - In Regard to Jang et al.

PMID- 30238906
TI  - Preface.

PMID- 30238905
TI  - In Reply to Lin and Golden.

PMID- 30238908
TI  - Just Say No to Testing.

PMID- 30238907
TI  - The tobacco endgame: The neglected role of place and environment.
AB  - An increasing number of countries across the world are planning for the
      eradication of the tobacco epidemic. The actions necessary to realise this
      ambition have been termed the tobacco endgame. The focus of this paper is on the
      intersection between the tobacco endgame with place, a neglected theme in recent
      academic and policy debates. We begin with an overview of the key themes in the
      literature on endgame strategies before detailing the international landscape of
      engame initiatives, paying particular attention to the opportunities and
      challenges of endgame strategies in low and middle income countries. Finally, we
      critically assess the current endgame debates and suggest a novel agenda for
      integrating geographical perspectives into research on the endgame that provides
      enhanced understanding of the challenges associated with this important global
      health vision.

PMID- 30238909
TI  - Use of Interpreter Services in the Emergency Department.

PMID- 30238910
TI  - Letter to the editor: comment on 'Timing of PROTein INtake and clinical outcomes
      of adult critically ill patients on prolonged mechanical VENTilation: The
      PROTINVENT retrospective study'.

PMID- 30238911
TI  - The care of VIPs in the emergency department: Triage, treatment and ethics.
AB  - People identified as Very Important Persons (VIPs) often present or are referred
      to the Emergency Department (ED). Celebrities are a small subset of this group,
      but many others are included. Triage of these patients, including occasional
      prioritization, creates practical and ethical challenges. Treatment also provides
      challenges with the risks of over testing, overtreatment, over consultation, and
      over or under admission to the hospital. This article presents a practical and
      ethical framework for addressing the care of VIPs in the ED.

PMID- 30238912
TI  - Chest wall hematoma after central venous hemodialysis catheter insertion.
AB  - There were few case reports discuss about iatrogenic chest wall hematoma.
      Although it is rare life threatening, it still can result in significant
      morbidity. A 68-year-old woman with histories of end-stage renal disease under
      regular hemodialysis and congestive heart failure was sent to our emergency
      department because of progression of ecchymosis over the anterior chest wall a
      few hours after hemodialysis. The right subclavian hemodialysis catheter was
      inserted for hemodialysis on the same day. She did not have a history of bleeding
      disorders and was not taking any antiplatelet or anticoagulant agents.
      Additionally, she had no recent trauma episodes. Physical examination revealed a
      large ecchymosis over the anterior right chest wall with swelling and tenderness.
      Blood examination showed no specific finding. Contrast-enhanced computed
      tomography of the chest revealed a hyperdense lesion with extravasation over the
      right chest wall, suggesting the presence of a hematoma with active bleeding.
      Local compression was applied. However, hematoma expansion was still noted.
      Therefore, we consulted a thoracic surgeon concerning surgical intervention.
      During the operation, active bleeding of the intramuscular arterial branch of the
      right pectoralis major was encountered. After surgical repair, no more bleeding
      was noted. It is important to confirm the possible cause of chest wall hematoma.
      Treating the underlying disease and discontinuing anticoagulation and
      antiplatelet agents should be considered. For iatrogenic chest wall hematoma,
      bleeding control should be the priority. Contrast-enhanced computed tomography
      could be arranged if there are no contraindications.

PMID- 30238913
TI  - Luxatio erecta humeri with humeral greater tuberosity fracture and axillary nerve
      injury.
AB  - Luxatio erecta humeri is the rarest type of glenohumeral dislocation, which has
      been reported to be associated with humeral fracture, rotator cuff tear and
      neurovascular injury. To our knowledge, a single-sided acute inferior
      glenohumeral dislocation associated with humeral greater tuberosity fracture and
      axillary nerve injury has not yet been reported. Here, we reported a traumatic
      first-time inferior shoulder dislocation from a construction worker who got
      hyperflexion of the left shoulder when fell and grasped the railing causing. The
      patient underwent traction counter-traction closed reduction followed by proper
      immobilization, and rehabilitation therapy. At thirteen months follow-up, the
      patient had returned to the workload that required high stress on shoulder joint
      with an excellent outcome.

PMID- 30238914
TI  - AGEP from a dog bite treated with Ibuprofen.
AB  - BACKGROUND: Acute Generalized Exanthematous Pustulosis (AGEP) is a rare
      dermatologic reaction characterized by an erythematous rash with pustular
      erosions, fever and leukocytosis. Although most often secondary to antibiotic
      use, AGEP has also been associated with many drugs. A thorough literature search
      showed only four previously documented cases of ibuprofen-associated AGEP, and
      one case of dog bite-associated AGEP. CASE REPORT: We present the case of a 46
      year old Caucasian female who developed AGEP after self-treating with ibuprofen
      for a dog bite. CONCLUSION: In the clinical setting this rash is often dramatic
      and illuminating the causative agent can be a diagnostic challenge. Our case
      represents a rare cause of AGEP and an important finding for current
      practitioners.

PMID- 30238916
TI  - Characterization of relapsing-remitting multiple sclerosis patients using support
      vector machine classifications of functional and diffusion MRI data.
AB  - Multiple Sclerosis patients' clinical symptoms do not correlate strongly with
      structural assessment done with traditional magnetic resonance images. However,
      its diagnosis and evaluation of the disease's progression are based on a
      combination of this imaging analysis complemented with clinical examination.
      Therefore, other biomarkers are necessary to better understand the disease. In
      this paper, we capitalize on machine learning techniques to classify relapsing
      remitting multiple sclerosis patients and healthy volunteers based on machine
      learning techniques, and to identify relevant brain areas and connectivity
      measures for characterizing patients. To this end, we acquired magnetic resonance
      imaging data from relapsing-remitting multiple sclerosis patients and healthy
      subjects. Fractional anisotropy maps, structural and functional connectivity were
      extracted from the scans. Each of them were used as separate input features to
      construct support vector machine classifiers. A fourth input feature was created
      by combining structural and functional connectivity. Patients were divided in two
      groups according to their degree of disability and, together with the control
      group, three group pairs were formed for comparison. Twelve separate classifiers
      were built from the combination of these four input features and three group
      pairs. The classifiers were able to distinguish between patients and healthy
      subjects, reaching accuracy levels as high as 89% +/- 2%. In contrast, the
      performance was noticeably lower when comparing the two groups of patients with
      different levels of disability, reaching levels below 63% +/- 5%. The brain
      regions that contributed the most to the classification were the right occipital,
      left frontal orbital, medial frontal cortices and lingual gyrus. The developed
      classifiers based on MRI data were able to distinguish multiple sclerosis
      patients and healthy subjects reliably. Moreover, the resulting classification
      models identified brain regions, and functional and structural connections
      relevant for better understanding of the disease.

PMID- 30238917
TI  - Cerebrospinal fluid volumetric net flow rate and direction in idiopathic normal
      pressure hydrocephalus.
AB  - The aim of the present study was to examine cerebrospinal fluid (CSF) volumetric
      net flow rate and direction at the cranio-cervical junction (CCJ) and cerebral
      aqueduct in individuals with idiopathic normal pressure hydrocephalus (iNPH)
      using cardiac-gated phase-contrast magnetic resonance imaging (PC-MRI). An in
      depth, pixel-by-pixel analysis of regions of interest from the CCJ and cerebral
      aqueduct, respectively, was done in 26 iNPH individuals, and in 4 healthy
      subjects for validation purposes. Results from patients were compared with over
      night measurements of static and pulsatile intracranial pressure (ICP). In iNPH,
      CSF net flow at CCJ was cranially directed in 17/22 as well as in 4/4 healthy
      subjects. Estimated daily CSF volumetric net flow rate at CCJ was 6.9 +/- 9.9
      L/24 h in iNPH patients and 4.5 +/- 5.0 L/24 h in healthy individuals. Within the
      cerebral aqueduct, the CSF net flow was antegrade in 7/21 iNPH patients and in
      4/4 healthy subjects, while it was retrograde (i.e. towards ventricles) in 14/21
      iNPH patients. Estimated daily CSF volumetric net flow rate in cerebral aqueduct
      was 1.1 +/- 2.2 L/24 h in iNPH while 295 +/- 53 mL/24 h in healthy individuals.
      Magnitude of cranially directed CSF net flow in cerebral aqueduct was highest in
      iNPH individuals with signs of impaired intracranial compliance. The study
      results indicate CSF flow volumes and direction that are profoundly different
      from previously assumed. We hypothesize that spinal CSF formation may serve to
      buffer increased demand for CSF flow through the glymphatic system during sleep
      and during deep inspiration to compensate for venous outflow.

PMID- 30238915
TI  - Ketamine influences the locus coeruleus norepinephrine network, with a dependency
      on norepinephrine transporter genotype - a placebo controlled fMRI study.
AB  - BACKGROUND: Ketamine is receiving increasing attention as a rapid-onset
      antidepressant in patients suffering from major depressive disorder (MDD) with
      treatment resistance or severe suicidal ideation. Ketamine modulates several
      neurotransmitter systems, including norepinephrine via the norepinephrine
      transporter (NET), both peripherally and centrally. The locus coeruleus (LC),
      which has high NET concentration, has been attributed to brain networks involved
      in depression. Thus we investigated the effects of single-dose of racemic
      ketamine on the LC using resting state functional MRI. METHODS: Fifty-nine
      healthy participants (mean age 25.57 +/- 4.72) were examined in a double-blind,
      randomized, placebo-controlled study with 7 Tesla MRI. We investigated the
      resting state functional connectivity (rs-fc) of the LC before and one hour after
      subanesthetic ketamine injection (0.5 mg/kg), as well as associations between its
      rs-fc and a common polymorphism in the NET gene (rs28386840). RESULTS: A
      significant interaction of drug and time was revealed, and post hoc testing
      showed decreased rs-fc between LC and the thalamus after ketamine administration
      compared with baseline levels, including the mediodorsal, ventral anterior,
      ventral lateral, ventral posterolateral and centromedian nuclei. The rs-fc
      reduction was more pronounced in NET rs28386840 [AA] homozygous subjects than in
      [T] carriers. CONCLUSIONS: We demonstrated acute rs-fc changes after ketamine
      administration in the central node of the norepinephrine pathway. These findings
      may contribute to understanding the antidepressant effect of ketamine at the
      system level, supporting modes of action on networks subserving aberrant arousal
      regulation in depression.

PMID- 30238920
TI  - IgG lymphoplasmacytic lymphoma: a case report.
AB  - Lymphoplasmacytic lymphoma is rare. Although most cases of LPL are Waldenstrom
      macroglobulinemia associated with an immunoglobulin M, there are exceptions.
      Indeed, few cases are immunoglobulin A-secreting or immunoglobulin G-secreting.
      These cases are poorly described and raise diagnostic difficulties. The purpose
      of this article is to describe an IgG lymphoplamacytic lymphoma case diagnosed
      recently in the hematology laboratory University Hospital of Toulouse.

PMID- 30238918
TI  - Typical asymmetry in the hemispheric activation during an fMRI verbal
      comprehension paradigm is related to better performance in verbal and non-verbal
      tasks in patients with epilepsy.
AB  - Chronic exposure to seizures in patients with left hemisphere (LH) epileptic
      focus could favor higher activation in the contralateral hemisphere during
      language processing, but the cognitive effects of this remain unclear. This study
      assesses the relationship between asymmetry in hemispheric activation during
      language fMRI and performance in verbal and non-verbal tasks. Whereas prior
      studies primarily used fMRI paradigms that favor frontal lobe activation and less
      prominent activation of the medial or superior temporal lobes, we used a verbal
      comprehension paradigm previously demonstrated to activate reliably receptive
      language areas. Forty-seven patients with drug-resistant epilepsy candidates for
      surgery underwent a multidisciplinary assessment, including a comprehensive
      neuropsychological evaluation and an fMRI verbal comprehension paradigm. Patients
      were distributed in two groups depending on laterality indexes (LI): typical
      hemispheric asymmetry (unilateral left activation preponderance; n = 23) and
      atypical hemispheric asymmetry (bilateral or unilateral right preponderance; n =
      24). Right-handedness and right hemisphere (RH) focus were significant predictors
      of typical asymmetry. Patients with typical activation pattern presented better
      performance intelligence quotient and verbal learning than patients with atypical
      hemispheric asymmetry (for all, p < 0.014). Patients with LH focus had more
      frequently atypical hemispheric asymmetry than patients with RH focus (p = 0.05).
      Specifically, they showed lower LI and this was related to worse performance in
      verbal and non-verbal tasks. In conclusion, an increased activation of homologous
      RH areas for verbal comprehension processing could imply a competition of
      cognitive resources in the performance of the same task, disrupting cognitive
      performance.

PMID- 30238921
TI  - Auer Rod-Like Inclusions in B-cell prolymphocytic leukemia.

PMID- 30238919
TI  - MEG resting-state oscillations and their relationship to clinical symptoms in
      schizophrenia.
AB  - Neuroimaging studies suggest that schizophrenia is characterized by disturbances
      in oscillatory activity, although at present it remains unclear whether these
      neural abnormalities are driven by dimensions of symptomatology. Examining
      different subgroups of patients based on their symptomatology is thus very
      informative in understanding the role of neural oscillation patterns in
      schizophrenia. In the present study we examined whether neural oscillations in
      the delta, theta, alpha, beta and gamma bands correlate with positive and
      negative symptoms in individuals with schizophrenia (SZ) during rest. Resting
      state brain activity of 39 SZ and 25 neurotypical controls was recorded using
      magnetoencephalography. Patients were categorized based on the severity of their
      positive and negative symptoms. Spectral analyses of beamformer data revealed
      that patients high in positive symptoms showed widespread low alpha power, and
      alpha power was negatively correlated with positive symptoms. In contrast,
      patients high in negative symptoms showed greater beta power in left hemisphere
      regions than those low in negative symptoms, and beta power was positively
      correlated with negative symptoms. We further discuss these findings and suggest
      that different neural mechanisms may underlie positive and negative symptoms in
      schizophrenia.

PMID- 30238922
TI  - Targeted Next Generation Sequencing of MLH1, MSH2, and MSH6 Genes in Patients
      with Endometrial Carcinoma <50 Years of Age.
AB  - BACKGROUND: Lynch syndrome (LS), which is an inherited cancer disorder, has an
      increased lifetime risk for various cancers. Endometrial cancer (EC) is the most
      common extra-colonic cancer in LS. Guidelines recommend that patients with EC
      diagnosed under 50 years of age should be evaluated for LS. Molecular analysis of
      mismatch repair (MMR) genes and EPCAM gene is required for a definitive diagnosis
      of LS. AIMS: The purpose of this study was to report the mutation analysis of MMR
      genes using targeted next generation sequencing (NGS) in patients having EC
      diagnosed <50 years of age as the first study from Turkey, to our knowledge.
      STUDY DESIGN: Retrospective cross-sectional study. METHODS: Seventy-nine patients
      with EC diagnosed <50 years of age underwent genetic counseling. They were
      selected among 1094 consecutive EC patients between 2006 and 2017. Molecular
      analysis of MLH1, MSH2, and MSH6 genes was performed in 79 patients by using NGS.
      And also, deletion/duplication analysis of MMR genes and EPCAM gene was performed
      in 79 patients by using multiplex ligation-dependent probe amplification (MLPA)
      method. RESULTS: Germline testing of MMR genes was performed in 79 EC patients.
      LS was confirmed in 4 patients (5%; 4/79). A total of 14 variants (6 in MSH2, 5
      in MLH1, 3 in MSH6 genes) were found in 14 patients. Four variants were assessed
      as pathogenic/likely pathogenic, 10 variants as variants of uncertain
      significance (VUS). CONCLUSION: This study emphasized that Lynch syndrome should
      be investigated in patients having EC diagnosed under 50 years of age because of
      increased lifetime risk for various cancers and this study determined the
      mutation frequency in MMR genes as the first time in Turkish patients with EC
      diagnosed <50 years of age by revealing both known and novel variants using NGS.

PMID- 30238923
TI  - The Effect of Chemerin on Cardiac Parameters and Gene Expressions in Isolated
      Perfused Rat Heart.
AB  - BACKGROUND: Chemerin is a novel chemoattractant adipokine, expressed in
      cardiovascular system and its receptor has also been detected in epicardial
      adipose tissue. AIMS: The objective of this research is to determine the effects
      of chemerin on the cardiac parameters and gene expressions, in isolated perfused
      rat heart. STUDY DESIGN: Animal experiment. METHODS: The hearts were retrogradely
      perfused with Langendorff technique to measure cardiac parameters. 10, 100 and
      1000 nM doses of chemerin were acute treated to the experimental groups. In
      another group, 10 MUM L-NAME was given for 5 minutes before 1000 nM chemerin
      administration. Real-time PCR was performed for detecting expression of target
      genes. RESULTS: All doses of chemerin significantly decreased LVDP (max 35.33 ?%,
      p<0.001), and +dP/dtmax (max 31.3 ?%, p<0.001), which are the indexes of cardiac
      contractile force. In addition, chemerin at a dose of 1000 nM reduced coronary
      flow (max 31 ?%, p<0.001). L-NAME antagonized the negative inotropic effect of
      chemerin on contractility. Chemerin induced 2.16 fold increase of eNOS mRNA and,
      also, increased cGMP levels (p<0.001) but decreased PI3Kgamma gene expression
      (1.8 fold, p<0.001). Furthermore, all doses of chemerin decreased CaV1.2 gene
      expression (1.69 fold, p<0.001). CONCLUSION: We suggest that acute chemerin
      treatment induces a negative inotropic action with the involvement of NO pathway,
      CaV1.2 and PI3Kgamma on isolated rat heart.

PMID- 30238925
TI  - Learning SPECT detector angular response function with neural network for
      accelerating Monte-Carlo simulations.
AB  - A method to speed up [Formula: see text] simulations of single photon emission
      computed tomography (SPECT) imaging is proposed. It uses an artificial neural
      network (ANN) to learn the angular response function (ARF) of a collimator
      detector system. The ANN is trained once from a complete simulation including the
      complete detector head with collimator, crystal, and digitization process. In the
      simulation, particle tracking inside the SPECT head is replaced by a plane.
      Photons are stopped at the plane and the energy and direction are used as input
      to the ANN, which provides detection probabilities in each energy window.
      Compared to histogram-based ARF, the proposed method is less dependent on the
      statistics of the training data, provides similar simulation efficiency, and
      requires less training data. The implementation is available within the GATE
      platform.

PMID- 30238924
TI  - The influence of prior pronunciations on sensorimotor cortex activity patterns
      during vowel production.
AB  - OBJECTIVE: In recent years, brain-computer interface (BCI) systems have been
      investigated for their potential as a communication device to assist people with
      severe paralysis. Decoding speech sensorimotor cortex activity is a promising
      avenue for the generation of BCI control signals, but is complicated by
      variability in neural patterns, leading to suboptimal decoding. We investigated
      whether neural pattern variability associated with sound pronunciation can be
      explained by prior pronunciations and determined to what extent prior speech
      affects BCI decoding accuracy. APPROACH: Neural patterns in speech motor areas
      were evaluated with electrocorticography in five epilepsy patients, who performed
      a simple speech task that involved pronunciation of the /i/ sound, preceded by
      either silence, the /a/ sound or the /u/ sound. MAIN RESULTS: The neural pattern
      related to the /i/ sound depends on previous sounds and is therefore associated
      with multiple distinct sensorimotor patterns, which is likely to reflect
      differences in the movements towards this sound. We also show that these patterns
      still contain a commonality that is distinct from the other vowel sounds (/a/ and
      /u/). Classification accuracies for the decoding of different sounds do increase,
      however, when the multiple patterns for the /i/ sound are taken into account.
      Simply including multiple forms of the /i/ vowel in the training set for the
      creation of a single /i/ model performs as well as training individual models for
      each /i/ variation. SIGNIFICANCE: Our results are of interest for the development
      of BCIs that aim to decode speech sounds from the sensorimotor cortex, since they
      argue that a multitude of cortical activity patterns associated with speech
      movements can be reduced to a basis set of models which reflect meaningful
      language units (vowels), yet it is important to account for the variety of neural
      patterns associated with a single sound in the training process.

PMID- 30238926
TI  - Should dose from small fields be limited for dose verification procedures?:
      uncertainty versus small field dose in VMAT treatments.
AB  - Over the years, radiotherapy treatments have become more complex and conformal,
      leading to an increased use of small field segments in volumetric modulated arc
      therapy (VMAT) arcs. The impact of small field dose inaccuracy on dose
      verification methods has not been studied yet. The aim of this work is therefore
      to quantify the relationship between the uncertainty of a 2D pre-treatment dose
      prediction model and the proportion of dose coming from small fields in VMAT arcs
      for a range of clinical plans. The model evaluated in this work predicts 2D
      portal dose images (PDIs) without a patient or phantom in the beam. The
      uncertainty of the model was calculated through simulation of model parameter
      deviations. The proportion of dose from small fields in a VMAT arc was determined
      by comparing a PDI with only dose from small fields with the original PDI. The
      uncertainty and proportion of dose from small fields were calculated for 109 VMAT
      arcs (41 head and neck, 33 lung, 35 prostate). The correlation was assessed with
      a linear regression. There is a statistically significant positive correlation
      between the uncertainty of the model and the proportion of dose from small fields
      in a VMAT arc, for each treatment site individually, as well as for all tumor
      sites together. The strongest relationship is found for the prostate cases. As
      there is a positive relationship between the uncertainty of the 2D pre-treatment
      dose prediction model, it may be wise to limit the dose from small fields in VMAT
      arcs, to avoid additional uncertainty in the dose verification process.

PMID- 30238927
TI  - In vitro pharmacokinetic phantom for two-compartment modeling in DCE-MRI.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an established
      minimally-invasive method for assessment of extravascular leakage, hemodynamics,
      and tissue viability. However, differences in acquisition protocols, variety of
      pharmacokinetic models, and uncertainty on physical sources of MR signal hamper
      the reliability and widespread use of DCE-MRI in clinical practice. Measurements
      performed in a controlled in vitro setup could be used as a basis for
      standardization of the acquisition procedure, as well as objective evaluation and
      comparison of pharmacokinetic models. In this paper, we present a novel flow
      phantom that mimics a two-compartmental (blood plasma and extravascular
      extracellular space/EES) vascular bed, enabling systemic validation of
      acquisition protocols. The phantom consisted of a hemodialysis filter with two
      compartments, separated by hollow fiber membranes. The aim of this phantom was to
      vary the extravasation rate by adjusting the flow in the two compartments.
      Contrast agent transport kinetics within the phantom was interpreted using two
      compartmental pharmacokinetic models. Boluses of gadolinium-based contrast-agent
      were injected in a tube network connected to the hollow fiber phantom; time
      intensity curves (TICs) were obtained from image series, acquired using a T1
      weighted DCE-MRI sequence. Under the assumption of a linear dilution system, the
      TICs obtained from the input and output of the system were then analyzed by a
      system identification approach to estimate the trans-membrane extravasation rates
      in different flow conditions. To this end, model-based deconvolution was employed
      to determine (identify) the impulse response of the investigated dilution system.
      The flow rates in the EES compartment significantly and consistently influenced
      the estimated extravasation rates, in line with the expected trends based on
      simulation results. The proposed phantom can therefore be used to model a two
      compartmental vascular bed and can be employed to test and optimize DCE-MRI
      acquisition sequences in order to determine a standardized acquisition procedure
      leading to consistent quantification results.

PMID- 30238928
TI  - Slow normal modes of proteins are accurately reproduced across different
      platforms.
AB  - The Protein data bank (PDB) (Berman et al 2000 Nucl. Acids Res. 28 235-42)
      contains the atomic structures of over 105 biomolecules with better than 2.8 A
      resolution. The listing of the identities and coordinates of the atoms comprising
      each macromolecule permits an analysis of the slow-time vibrational response of
      these large systems to minor perturbations. 3D video animations of individual
      modes of oscillation demonstrate how regions interdigitate to create cohesive
      collective motions, providing a comprehensive framework for and familiarity with
      the overall 3D architecture. Furthermore, the isolation and representation of the
      softest, slowest deformation coordinates provide opportunities for the
      development of mechanical models of enzyme function. The eigenvector
      decomposition, therefore, must be accurate, reliable as well as rapid to be
      generally reported upon. We obtain the eigenmodes of a 1.2 A 34 kDa PDB entry
      using either exclusively heavy atoms or partly or fully reduced atomic sets;
      Cartesian or internal coordinates; interatomic force fields derived either from a
      full Cartesian potential, a reduced atomic potential or a Gaussian distance
      dependent potential; and independently developed software. These varied
      technologies are similar in that each maintains proper stereochemistry either by
      use of dihedral degrees of freedom which freezes bond lengths and bond angles, or
      by use of a full atomic potential that includes realistic bond length and angle
      restraints. We find that the shapes of the slowest eigenvectors are nearly
      identical, not merely similar.

PMID- 30238929
TI  - Validation of the MCNP6 code for SFR shielding design analysis.
AB  - In this paper, the uncertainty of the Monte Carlo code MCNP6 for the sodium
      cooled fast reactor (SFR) shielding design is studied. Shielding analysis, which
      ensures the radiation safety of the core design, is challenging for the Monte
      Carlo modeling because it is associated with large uncertainties. In order to
      evaluate the performance of the MCNP6 relative to the shielding design of the
      SFR, four SFR shielding benchmarks from the Shielding Integral Benchmark Archive
      Database benchmark suite, i.e. JANUS Phase VIII, SDT12, EURAC_Na and HARMO_Na
      were selected and analysed. In this research, the weight window variance
      reduction technique and the neutron data library ENDF/B-VII.1 were used in the
      modeling of the benchmark problems. The results and the validation of the MCNP6
      models with the available measurement data are presented in this paper. These
      results contribute to the assessment of radiological protection and shielding
      design of the Korean Prototype Gen-IV Sodium-cooled Fast Reactor.

PMID- 30238930
TI  - Errata: Internal doses from radionuclides and their health effects following the
      Fukushima accident (J. Radiol. Prot. 2018 38 1253-68).
AB  - This article presents errata on a published article.

PMID- 30238931
TI  - Dysregulated interferon-gamma and interleukin-2 synthesis in peripheral blood T
      cells in quiescent systemic lupus erythematosus is dependent on the affected T
      cell receptor zeta chain expression.

PMID- 30238932
TI  - Esophageal pH and impedance reflux parameters in relation to body mass index,
      obesity-related hormones, and bariatric procedures.
AB  - Introduction Obese patients have a higher risk of gastroesophageal reflux disease
      (GERD), but obesity-related hormonal changes associated with GERD and the effects
      of bariatric therapy on reflux are unclear. Objectives The aim of the study was
      to assess reflux parameters in relation to bariatric therapy and hormonal changes
      in obese patients. Patients and methods This prospective observational study with
      a 1-year follow-up included 53 obese patients undergoing bariatric therapies.
      Esophageal pH and impedance monitoring tests were performed and circulating
      hormone levels were analyzed. Results Esophageal acid exposure time (%AET) and
      the number of refluxes correlated positively with body mass index. There were
      several significant, although weak, correlations of pH and impedance parameters
      with ghrelin and omentin levels. Patients with abnormal %AET had lower ghrelin
      levels and those with abnormal reflux number had lower omentin levels than
      patients with normal parameters. Although we observed certain changes including
      increased %AET and bolus clearance time (BCT) after laparoscopic sleeve
      gastrectomy, a reduced BCT and number of refluxes after gastric band, and
      nonsignificant changes after intragastric balloon, the overall bariatric therapy
      did not significantly impact on the final GERD diagnosis. GERD before and after
      therapy was present in 42% of patients. De novo GERD developed in 17.8% of
      patients, while a similar percentage of patients with initial GERD had normal pH
      and impedance after therapy. Patients with de novo or persistent GERD had a
      similar percentage of weight loss as patients without GERD. Conclusions Bariatric
      therapy and percentage of weight loss do not significantly affect GERD. The
      observed hormonal changes alone do not fully explain the high prevalence of GERD
      in obese patients.

PMID- 30238934
TI  - Descemet membrane endothelial keratoplasty with stromal rim (DMEK-S) in
      complicated patients.
AB  - PURPOSE: To evaluate the outcomes of the hybrid technique of posterior lamellar
      keratoplasty (Descemets' membrane endothelial keratoplasty with stromal rim, DMEK
      S) in eyes with multiple ocular pathologies. METHODS: A retrospective case
      control study of the consecutive group of all eyes with combined ocular
      pathologies which underwent DMEK-S keratoplasty. We evaluated the number of pre-
      and post-operative complications; uncorrected distance visual acuity (UDVA);
      corrected distance visual acuity (CDVA) and endothelial cell density (ECD). The
      first group (Group 1 - 100 eyes) was compared to a control group of eyes (Group 2
      - 145 eyes) without combined ocular pathologies, which were operated throughout
      the same time period. Comparisons were made in the 12th month of the follow-up.
      RESULTS: Both the UDVA and the CDVA statistical values 12 months after the
      surgery were significantly better in Group 2. ECD was comparable in both groups.
      The number of complications during surgery was considerably higher in Group 1,
      where a certain type of complication occurred in 15 eyes (15%), while in Group 2
      this complication occurred only in 9 eyes (6.2%). In Group 1 a slightly higher
      number of rebubbling cases (52% vs. 48.3%) occurred, as well as more than twice
      as many cases of primary graft failure (34% vs. 15.7%) compared to Group 2.
      CONCLUSION: DMEK-S - hybrid endothelial transplantation in complicated eyes in
      the evaluated group of patients led to a noticeable improvement of visual acuity.
      When compared to surgeries in uncomplicated eyes, DMEK-S results in a higher rate
      of postoperative complications, especially graft detachment and primary failure.

PMID- 30238933
TI  - MicroRNA let-7c-5p Suppressed Lipopolysaccharide-Induced Dental Pulp Inflammation
      by Inhibiting Dentin Matrix Protein-1-Mediated Nuclear Factor kappa B (NF-kappaB)
      Pathway In Vitro and In Vivo.
AB  - BACKGROUND Let-7c-5p is down-regulated in dental pulp tissues in inflammatory
      disorders. The microRNA (miR) molecule shows an anti-inflammation potential due
      to its direct regulation of dentin matrix protein-1 (DMP1), which promotes
      inflammation changes in dental pulp tissues. In the present study, the effect of
      let-7c-5p on lipopolysaccharide (LPS)-induced pulpitis was detected and the
      associated mechanism was explored. MATERIAL AND METHODS Dental pulp stem cells
      (DPSCs) were isolated from rat dental tissues, infected with let-7c-5p lentivirus
      particles, and subjected to LPS administration to induce inflammation. Then, the
      effect of let-7c-5p overexpression on LPS-induced impairments on DPSCs were
      detected and the mechanism was explained by focusing on the DMP1 expression and
      NF-kappaB pathway. The role of DMP1 in the anti-inflammation effect of let-7c-5p
      was assessed by incubating let-7c-5p-expressed DPSCs with DMP1 protein. The
      results of in vitro assays were verified in LPS-induced rat pulpitis models.
      RESULTS LPS administration increased the production of IL-1beta and TNF-alpha and
      decreased DPSCs viability by increasing the expression of DMP1 and activating NF
      kappaB pathway. However, the induced expression of let-7c-5p relieved DPSCs from
      LPS-induced inflammation and suppressed DMP1 as well as NF-kappaB pathway. The
      incubation of let-7c-5p-expressed DPSCs with DMP1 protein blocked the effect of
      let-7c-5p. In in vivo experiments, the injection of let-7c-5p attenuated LPS
      induced pulpitis by inhibiting DMP1-mediated NF-kappaB pathway. CONCLUSIONS
      Findings outlined in the current study demonstrated the dental pulp protecting
      function of let-7c-5p during LPS-induced inflammation, which was exerted by
      inhibiting the DMP1-mediated NF-kappaB pathway.

PMID- 30238935
TI  - Gestational surrogacy in the Czech Republic.
AB  - BACKGROUND: Gestational surrogacy, is a treatment option for women with certain
      clearly defined medical problems, usually an absent uterus, to help them have
      their own genetic children. The aim of our study was to review, evaluate and
      share our experience and outcomes over the last 13 years of the largest surrogacy
      program in the Czech republic. METHODS: A total of 75 intended mothers and 82
      surrogate mothers participated in this study. A retrospective cohort study was
      performed. Anonymized data were collected on 130 cycles of gestational surrogate
      (2004-2017) directly from the Clinic database. RESULTS: We performed 130 in vitro
      fertilization cycles with gestational surrogacy which involved 73 fresh embryo
      transfers and 57 frozen embryo transfers. We achieved 57 (43.9%) pregnancies and
      42 (32.3%) live births. The rate of multiple pregnancies was only 2.3 %. The most
      common indication for using was an absent or damaged uterus (65%), followed by
      medical conditions precluding pregnancy (23%) and repeated in vitro fertilization
      cycles or pregnancy failure (12%). CONCLUSION: In the 14 years of our experience,
      we have shown that treatment of young women with specific indications for
      gestational surrogacy is beneficial, successful and relatively free of
      complications. However, it is imperative to follow the medical indications for
      this treatment and specialist recommendations.

PMID- 30238936
TI  - Changes in cholesterol metabolism during acute upper gastrointestinal bleeding:
      liver cirrhosis and non cirrhosis compared.
AB  - BACKGROUND: Cholesterol is derived via de novo synthesis and dietary absorption.
      Both processes can be monitored by determination of non-cholesterol sterol
      concentrations (lathosterol for synthesis; sitosterol and campesterol for
      absorption). The hypocholesterolemia that occurs during acute illness is a result
      of a multifactorial inability to compensate for the increased needs for this
      metabolite. The aim of this study was to examine the plasma cholesterol profile
      and both processes of cholesterol acquisition during acute upper gastrointestinal
      haemorrhage with emphasis on liver cirrhosis. MATERIAL AND METHODS: Thirty five
      patients with acute upper gastrointestinal bleeding (cirrhosis n=14, non
      cirrhosis n=21) were evaluated over a 6 day period. The control cohort consisted
      of 100 blood donors. Serum concentrations of total, LDL (low-density lipoprotein)
      and HDL (high-density lipoprotein) cholesterol were measured enzymatically.
      Sterol concentrations were analysed using gas chromatography, data were
      statistically analysed. RESULTS: In all patients, we found lower plasma levels of
      total cholesterol (P<0.001) and decrease of LDL and HDL cholesterol. Patients had
      also significantly lower plasma levels of sterol concentrations. While the
      differences in cholesterol profile between cirrhotic and non-cirrhotic bleeding
      were significant only in HDL cholesterol (P<0.001), comparison of non-cholesterol
      sterols was statistically significant (P<0.001) in all measured parameters.
      CONCLUSION: Our results showed substantial abnormalities in the cholesterol
      plasma profile including both the processes of cholesterol acquisition in
      patients with upper acute gastrointestinal bleeding. The patients with or without
      liver cirrhosis had similar trends in cholesterol plasma levels. Depression of
      cholesterol synthesis was, however, prolonged in the cirrhotic group and the data
      also suggest a different phytosterol metabolism.

PMID- 30238937
TI  - Triptycene molecular rotors mounted on metallofullerene Sc3C2@C80 and their spin
      rotation couplings.
AB  - Molecular machines have received considerable attention due to their various
      applications. Except for mechanical motion, it is essential to design advanced
      molecular machines with integrated functions. In this study, the triptycene rotor
      has been covalently linked to paramagnetic metallofullerene Sc3C2@C80 with an
      unpaired electron spin, resulting in a coupled system between spin flip and rotor
      speed. Two types of triptycene rotors were employed, one is pristine triptycene
      and another one has a sterically hindered methyl group. Temperature-dependent
      electron paramagnetic resonance (EPR) spectroscopy revealed that spin-rotor
      coupling can be modulated by the rotation speed of triptycene rotors, which was
      further illustrated by variable-temperature 1H NMR. EPR simulation revealed that
      the rotations of the attached triptycene rotors can greatly influence the spin
      relaxation and spin-metal hyperfine couplings of Sc3C2@C80, realizing remote
      control on neighboring electron spin states. These findings of the coupled system
      between the molecular rotor and spin flip would provide an approach to design
      advanced molecular machines with magnetic function.

PMID- 30238938
TI  - Does cage quantum delocalisation influence the translation-rotational bound
      states of molecular hydrogen in clathrate hydrate?
AB  - In this study, we examine the effect of a flexible description of the clathrate
      hydrate framework on the translation-rotation (TR) eigenstates of guest molecules
      such as molecular hydrogen. Traditionally, the water cage structure is assumed to
      be rigid, thus ignoring the quantum nature of hydrogen nuclei in the water
      framework. However, it has been shown that protons in a water molecule possess a
      marked delocalised character in many situations, ranging from water clusters to
      proton transfer in the bulk. In the case of water clathrates, all previous TR
      bound-state calculations of guest molecules consider that the caging water
      molecules are fixed at their equilibrium geometry. Only recently, a static
      investigation of the role of proton configurations was performed by Bacic and co
      workers by sampling a very large number of different static structures of water
      clathrates. Here, we investigate the importance of the rotational degrees of
      freedom of the water cage on the TR levels of the guest molecule using an
      efficient adiabatic decoupling scheme. Our approach combines rigid body diffusion
      Monte Carlo calculations for the description of the rotational degree of freedom
      of water molecules surrounding the guest molecular hydrogen to an efficient
      Smolyak sparse-grid technique for the calculation of the TR levels. This approach
      allows us to take into account the highly anharmonic nature of the rotational
      water motions in a high-dimensional system. The clathrate-induced splittings of
      the j = 1 rotational levels are much more sensitive to the quantum hydrogen
      delocalisation than the translational transitions. This result is in good
      agreement with the previous static study of Bacic and co-workers.

PMID- 30238939
TI  - Erratic charge transfer dynamics of Au/ZnTiO3 nanocomposites under UV and visible
      light irradiation and their related photocatalytic activities.
AB  - The present article presents an in-depth discussion on the state-of-the-art
      multifarious roles of Au nanoparticles and their associated charge anti
      recombination process in burgeoning photocatalysis research. Hexagonal-phase
      ZnTiO3 was fabricated through a sol-gel auto-combustion method by optimizing the
      calcination temperatures. To further improve the charge separation efficiency and
      visible light induced photocatalytic activity of pristine ZnTiO3, we designed a
      new type of Au/ZnTiO3 nanocomposite by a precipitation-deposition method. The
      photocatalytic activities of the Au/ZnTiO3 nanocomposites were substantiated by
      evaluating the rate of hydrogen evolution under both UV and visible light
      illumination. The photocatalytic activity of the Au/ZnTiO3 nanocomposites rises
      proportionally with an increase in Au content up to 1.5 wt% under UV light
      illumination and it produce around 285 MUmol h-1 of H2 which is approximately 2.6
      times higher than that produced by pristine ZnTiO3. Therefore, the Au
      nanoparticles present on the surface of ZnTiO3 act as electron acceptors, leading
      to an increase in the rate of generation and separation of charge carriers. This
      process helps to enhance the congregation of electrons on Au nanoparticles
      through the Schottky junction. The obtained results are very consistent with
      steady-state PL and UV light induced photocurrent measurements. Conversely, such
      a trend was not detected under visible light illumination. The visible light
      induced photocatalytic activity of Au/ZnTiO3 nanocomposites increases with a rise
      in Au content up to 1 wt% and thereafter decreases with further Au loading.
      Therefore, the initial increment in photocatalytic activity is due to the
      generation, separation and participation of a large number of SPR-induced charge
      carriers and thereafter decreases due to the recombination of SPR-generated
      charge carriers because of the formation of defect sites at the Au and ZnTiO3
      interface. That the excess Au loading causes the recombination of SPR charge
      carriers was well explained by undertaking SPR-induced TRPL analysis and this
      result is directly followed up with the results of visible light induced
      photocurrent and EIS measurements. The Au/ZnTiO3 nanocomposites with optimal Au
      loading (1 wt%) delivered an amazingly high rate of hydrogen evolution i.e. 108
      MUmol h-1 with an energy conversion efficiency of 7.14%, whereas pristine ZnTiO3
      shows negligible activity under visible light illumination.

PMID- 30238940
TI  - n-Type Ohmic contact and p-type Schottky contact of monolayer InSe transistors.
AB  - Owing to their few lateral dangling bonds and enhanced gate electrostatics, two
      dimensional semiconductors have attracted much attention for the fabrication of
      channels in next-generation field-effect transistors (FETs). Herein, combining
      first-principle band structure calculations with more precise quantum transport
      simulations, we systematically explore the interface properties between monolayer
      (ML) indium selenide (InSe) and a sequence of common electrodes in an FET. The ML
      InSe band structure is damaged by Sc, Au, Cr, Pt, and Pd electrodes but
      identifiable in contact with Ag, Cu, In, graphene and ML O-terminated Cr2C
      electrodes. A lateral n-type Schottky contact is generated with Sc, Au, Cr, Pt,
      Pd, and ML graphene electrodes owing to Fermi level pinning originating from the
      metal-induced gap states, which feature a pinning factor of 0.32. Luckily, a
      highly desirable lateral n-type Ohmic contact is generated with the Ag, Cu, and
      In electrodes. The calculated contact polarity is in agreement with the available
      experimental results using Au, Cr, ML graphene, Ag, and In as electrodes.
      Remarkably, a lateral p-type Schottky contact is generated with ML O-terminated
      Cr2C despite the very high work function of ML InSe. Therefore, this study offers
      a deeper understanding of ML InSe device interfaces and instructions for the
      design of ML InSe transistors.

PMID- 30238941
TI  - Relaxation of surface-tethered polymers under moderate confinement.
AB  - We study the relaxation of surface-tethered polymers in microchannels under
      moderate confinement (i.e. h ~ Rg, where h is the channel height and Rg is the
      radius of gyration of the polymer) by experiments with fluorescence-marked DNA
      molecules and coupled lattice-Boltzmann/molecular dynamics simulations. The
      determined scaling exponent suggests that the relaxation is dominated by Zimm
      dynamics with significant intra-chain hydrodynamic interactions. The relaxation
      of the DNA molecules is slower in shallower channels, indicating a pronounced
      effect of confinement on the longest relaxation time. An experimental correlation
      is obtained for the longest relaxation time as a function of the molecular
      contour length and the channel height. Good agreement between the experimental
      and the simulation results is found.

PMID- 30238942
TI  - Anti-cancer effects of wedelolactone: interactions with copper and subcellular
      localization.
AB  - Wedelactone (WL), a plant polyphenolic derivative of coumestan, represents a
      promising anti-cancer agent. The underlying mechanisms of its action are not
      fully understood and appear to involve interplay with copper ions. Herein, we
      examined coordination and redox interactions of WL with Cu2+ in phosphate buffer
      (pH 7), and in two breast cancer cell lines. EPR, UV-Vis and fluorescence
      spectroscopy showed that WL and Cu2+ build a coordination complex with 2 : 1
      stoichiometry and distorted tetrahedral geometry. WL showed strong fluorescence
      that was quenched by Cu2+. The sequestration of the intracellular copper pool
      with neocuproine led to a significant drop in the cytotoxic effects of WL,
      whereas the co-application of Cu2+ and WL and the formation of an extracellular
      complex suppressed both the cytotoxic effects of WL and copper loading.
      Fluorescence microscopy showed that WL is mainly localized in the cytosol and
      significantly less in the nuclei. WL fluorescence was stronger in cells
      pretreated with neocuproine, implying that the complex of WL and Cu2+ is formed
      inside the cells. WL caused a two-fold increase in the lysosomal level of copper
      as well as copper-dependent lysosome membrane permeabilization. On the other
      hand, the protective effects of overexpression of thioredoxin 1 imply that WL
      exerts the main oxidative impact inside the nucleus. The interactions of WL with
      copper may be essential for therapeutic performance and selectivity against
      cancer cells, taking into account that a number of cancer types, including breast
      cancer, exhibit increased intratumoral copper levels or altered copper
      distribution.

PMID- 30238943
TI  - Protonation-induced molecular permeation at the oil/water interface in an
      electric field.
AB  - As a common physicochemical phenomenon, protonation can cause molecules, atoms or
      ions with lone-pair electrons to become charged, and can further cause some
      changes in their physical and chemical properties. Our study first focused on the
      molecular protonation process and accompanying transitions of the oil/water
      interface properties in an electric field. The relationship between the
      protonation degree increment and applied voltage was proposed as a guide for
      controlling the protonation via applying an electric field. Besides the
      protonation degree, the water solubility of the oily target molecule obviously
      increased at 30 V for 600 s along with electric field-driven protonation. At the
      same time, the electrical conductivity and the underwater interface wettability
      of oil phase transitioned. These property transitions are anticipated to guide
      the further improvement and updating of promising protonation functions.

PMID- 30238944
TI  - Blueberry extract promotes longevity and stress tolerance via DAF-16 in
      Caenorhabditis elegans.
AB  - Blueberry is rich in bioactive phytochemicals with a wide of range of biological
      activities and health benefits. However, little is known about their effects on
      aging. The objectives of this study were to evaluate the effects of
      supplementation with a blueberry extract (BE) on lifespan and stress resistance
      using Caenorhabditis elegans (C. elegans) as a model. The mechanisms of these
      effects were explored using RNAi technology. The mean lifespan of C. elegans
      treated with BE at 50, 100, and 200 mg mL-1 was significantly increased by 22.2%,
      36.5%, and 44.4%, respectively, in a dose-dependent manner. In addition,
      supplementation with BE improved motility and decreased lipofuscin accumulation.
      C. elegans pretreated with BE were more resistant than untreated C. elegans to
      stresses (heat, ultraviolet-B radiation, and paraquat). Treatment with BE
      resulted in up-regulation of genes related to antioxidant systems, including sod
      3, cat-1, mev-1, skn-1, mek-1, nhr-8, and daf-16. Suppression of daf-16 by RNAi
      shortened the lifespan of C. elegans and inhibited the expression of sod-3,
      suggesting that BE may regulate sod-3 downstream of daf-16 to extend lifespan and
      stress resistance. Our findings revealed that, in C. elegans, BE can prolong the
      lifespan, improve health indexes, and enhance stress resistance.

PMID- 30238945
TI  - QM and ONIOM studies on thermally activated delayed fluorescence of copper(i)
      complexes in gas phase, solution, and crystal.
AB  - Herein, we have employed B3LYP and TD-B3LYP methods with the QM/MM approach to
      study the thermally activated delayed fluorescence (TADF) phenomenon of two Cu(i)
      complexes bearing 5-(2-pyridyl)-tetrazolate (PyrTet) and phosphine (POP) ligands
      in the gas phase, solution, and crystal form. On the basis of spectroscopic
      properties, ground- and excited-state geometric and electronic structures, and
      related radiative and nonradiative rates, we have found that (1) the S1 and T1
      excited states have clear metal-to-ligand charge transfer character from the
      Cu(i) atom to the PyrTet group; (2) the S1 and T1 states have a very small energy
      gap DeltaES1-T1, less than 0.18 eV, which makes the forward and reverse
      intersystem crossing ISC and rISC processes between the S1 and T1 states very
      efficient; and (3) the low-frequency vibrational modes related to the torsional
      motion of the POP and PyrTet groups are found to have significant Huang-Rhys
      factors and are responsible for the efficient ISC and rISC rates. However, the
      corresponding Huang-Rhys factors are remarkably suppressed in the crystal
      compared with those in the gas phase and in solution due to the rigidity of the
      crystal surroundings; as a result, the ISC and rISC rates are accordingly reduced
      slightly in the crystal. This comparison also demonstrates that the surrounding
      effects are very important for modulating the photophysical properties of the
      Cu(i) complexes. Finally, our work gives helpful insights into the TADF mechanism
      of the Cu(i) compounds, which could assist in rationally designing TADF materials
      with excellent performance.

PMID- 30238946
TI  - Modulation of thermal conductivity in single-walled carbon nanotubes by fullerene
      encapsulation: enhancement or reduction?
AB  - Fullerene encapsulation has been proven to be a powerful approach to enhance the
      mechanical and electronic properties of single-walled carbon nanotubes (SWCNTs).
      However, some discrepancies emerge in recent studies of the fullerene
      encapsulation effect on the thermal conductivity of SWCNTs. More specifically,
      most previous theoretical studies predicted slight enhancement in the thermal
      conductivity, but the recent experiment by Kodama et al. (Nat. Mat.16, 892, 2017)
      observed a clear reduction in the thermal conductivity of SWCNTs by fullerene
      encapsulation. We perform molecular dynamics simulations to revisit this issue,
      by comparatively investigating the thermal conductivity of the SWCNT (n, n) and
      the corresponding peapod (n, n) with n = 8, 9, 10, and 11. We find that the
      encapsulation can reduce the thermal conductivity of narrower SWCNTs with n = 8
      and 9, but it can slightly enhance the thermal conductivity of thicker SWCNTs
      with n = 10 and 11. The underlying mechanisms for these opposite effects are
      explored by analyzing the encapsulation induced structural deformation and the
      variation in the phonon dispersion of the SWCNT. We illustrate that the reduction
      effect observed in the recent experiment is related to the mechanism for
      reduction of the thermal conductivity for narrower SWCNTs here.

PMID- 30238947
TI  - Assembly of cellulose nanocrystals in a levitating drop probed by time-resolved
      small angle X-ray scattering.
AB  - Assembly of bio-based nano-sized particles into complex architectures and
      morphologies is an area of fundamental interest and technical importance. We have
      investigated the assembly of sulfonated cellulose nanocrystals (CNC) dispersed in
      a shrinking levitating aqueous drop using time-resolved small angle X-ray
      scattering (SAXS). Analysis of the scaling of the particle separation distance
      (d) with particle concentration (c) was used to follow the transition of CNC
      dispersions from an isotropic state at 1-2 vol% to a compressed nematic state at
      particle concentrations above 30 vol%. Comparison with SAXS measurements on CNC
      dispersions at near equilibrium conditions shows that evaporation-induced
      assembly of CNC in large levitating drops is comparable to bulk systems.
      Colloidal states with d vs. c scalings intermediate between isotropic dispersions
      and unidirectional compression of the nematic structure could be related to the
      biphasic region and gelation of CNC. Nanoscale structural information of CNC
      assembly up to very high particle concentrations can help to fabricate
      nanocellulose-based materials by evaporative methods.

PMID- 30238948
TI  - Strategies for the selective loading of patchy worm-like micelles with functional
      nanoparticles.
AB  - Block copolymer self-assembly in solution paves the way for the construction of
      well-defined compartmentalized nanostructures. These are excellent templates for
      the incorporation and stabilisation of nanoparticles (NPs), giving rise to highly
      relevant applications in the field of catalysis or sensing. However, the regio
      selective incorporation of NPs in specific compartments is still an issue,
      especially concerning the loading with different NP types. Using crystallisation
      driven self-assembly (CDSA), functional worm-like crystalline-core micelles
      (wCCMs) with a tailor-made, nanometre-sized patchy corona were prepared as
      versatile templates for the incorporation and stabilisation of metal and metal
      oxide NPs. Different strategies, like ligand exchange or co-precipitation of
      polymer stabilised NPs with one surface patch, were developed that allow the
      incorporation of NPs in specific regions of the patchy wCCM corona. Independent
      of the NP type and the incorporation method, the NPs showed no tendency for
      agglomeration and were fixed within the corona patches of the wCCMs. The binary
      loading of patchy micelles with metal and metal oxide NPs was realised by
      combining different loading strategies, yielding hybrids with homogeneously
      dispersed NPs guided by the patchy structure of the template.

PMID- 30238949
TI  - Efficient electrochemical transformation of CO2 to C2/C3 chemicals on
      benzimidazole-functionalized copper surfaces.
AB  - A simple and efficient catalyst, benzimidazole (BIMH)-modified copper foil, is
      developed to enhance the selective conversion of CO2 to C2/C3 products. The
      overall faradaic efficiency (FE) for CO2 reduction reaches 92.1% and the
      undesired hydrogen evolution reaction (HER) is lowered to a FE of 7% at -1.07
      VRHE.

PMID- 30238950
TI  - Three new Strandberg-type phenylphosphomolybdate supports for immobilizing
      horseradish peroxidase and their catalytic oxidation performances.
AB  - Three organic-inorganic hybrids containing Strandberg-type phenylphosphomolybdate
      anion [(C6H5PO3)2Mo5O15]4- with phenylphosphonate (PhP) centers, transition metal
      (TM) ions and 2,2'-biimidazole (H2biim) ligand, formulated as
      [(TM(H2biim)2)2(C6H5PO3)2Mo5O15].H2O (TM = Co and Cu, abbreviated as Co-(PhP)2Mo5
      and Cu-(PhP)2Mo5, respectively) and ([Ni(H2biim)3])2[(C6H5PO3)2Mo5O15].2H2O
      (abbreviated as Ni-(PhP)2Mo5), were self-assembled by simple hydrothermal methods
      and were systematically characterized through single-crystal X-ray diffraction
      and other physicochemical and spectroscopic methods, which demonstrated that TM
      H2biim complexes were firstly introduced into Strandberg-type
      organophosphomolybdate skeletons. Selecting the oxidation of cyclohexanol to
      cyclohexanone as a model reaction, using H2O2 as an oxidant, the catalytic
      oxidation activities of the Strandberg-type compounds were firstly evaluated.
      More importantly, these TM-(PhP)2Mo5 (TM = Co, Cu, Ni) compounds were employed to
      immobilize horseradish peroxidase (HRP), and showed high adsorption capacities
      for HRP. Laser scanning confocal microscope images showed that HRP adsorbed on
      the surfaces of the TM-(PhP)2Mo5 supports. Application of immobilized enzyme
      HRP/TM-(PhP)2Mo5 for the detection of H2O2 is also discussed.

PMID- 30238951
TI  - Detection of Escherichia coli bacteria by impact electrochemistry.
AB  - We report the redox mediated detection of Escherichia coli bacteria at carbon
      microelectrodes, using the impact electrochemistry technique. By employing
      N,N,N',N'-tetramethyl-para-phenylene-diamine (TMPD) as redox mediator a
      concentration dependency for bacteria impacts was observed, whereby its impact
      frequency is shown to be in good agreement with theoretically predicted values.

PMID- 30238962
TI  - Clinicopathological features and lymph node metastatic patterns of gastric mixed
      adenoneuroendocrine carcinoma.
AB  - AIMS: Mixed adenoneuroendocrine carcinoma (MANEC), also known as high- grade
      mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) in the World Health
      Organization (WHO) classification of tumors of the endocrine organs (2017), is a
      rare gastric malignancy. Here, we present 10 cases of gastric MANEC and analyse
      their clinicopathological features and lymph node metastatic patterns. METHODS
      AND RESULTS: Six patients were male, and four were female. The mean age of the
      patients was 67.9 years. Grossly, most tumors presented as ulcerative mass,
      located in gastric fundus or/and cardia. Microscopically, the neuroendocrine
      component, large cell neuroendocrine carcinoma in most cases (8/10), constituted
      30-70% of the whole tumor. It was diffusely positive for CD56 or/and
      synaptophysin in all cases, but negative for chromogranin A in 9 cases. Ki-67
      index was 50-80% in neuroendocrine component. The glandular component was
      moderately (6/10) or poorly (4/10) differentiated adenocarcinoma. Nine of 10
      cases were positive for lymph node metastasis, with pure neuroendocrine component
      (6/9), or pure glandular component (1/9), or mixed components (2/9). The patients
      were treated with surgery, combining with chemotherapy (4/10), radiotherapy
      (2/10) and immunotherapy (1/10). Five patients died from tumor progress, with an
      average survival time of 18.6 months. The dead cases had predominant
      neuroendocrine component in primary tumor or in metastatic lymph nodes.
      CONCLUSIONS: Neuroendocrine component may determine the clinical behavior and
      outcome in gastric MANEC. Different metastatic component makes the selection of
      chemotherapy protocol more challenging.

PMID- 30238963
TI  - Coffee consumption and work satisfaction among Scandinavian anaesthesiologists: A
      survey.
AB  - BACKGROUND: It is a common prejudice that anaesthetic doctors are believed to
      have high coffee consumption. In this study, we aimed to assess the association
      between coffee drinking and work satisfaction among Scandinavian
      anaesthesiologists. We hypothesised that coffee consumption was positively
      correlated with work satisfaction. METHODS: We invited anaesthesiologists
      attending the 34th congress of The Scandinavian Society of Anaesthesiology and
      Intensive Care Medicine in Malmo, Sweden, September 2017 to participate in a
      paper-based survey. We collected data on characteristics of the respondents,
      coffee drinking and work satisfaction, and compared coffee vs non-coffee drinkers
      with regard to work satisfaction scored on a modified Wong-Baker Faces Pain
      Rating Scale (Visual Analogue Scale from 0 to 10). RESULTS: A total of 271
      anaesthesiologists participated in the survey, of which 265 (97.7%) of the
      questionnaires contained valid data. Some 143 (54.0%) of the respondents were
      women, the median (interquartile range, IQR) age was 41.0 (35.0-49.5) years, and
      242 (91.3%) were coffee drinkers. Coffee drinkers consumed median 4.0 (IQR: 2.5
      5.0) cups of coffee daily. Overall work satisfaction was median 8 (IQR: 8-9),
      with no difference between respondents drinking coffee and those who did not
      (median 8 (IQR: 8-9) vs 8 (IQR: 8-9), Wilcoxon rank sum test, P = 0.62). Also, we
      found no association between work satisfaction and the number of cups of coffee
      consumed daily (r2  = 0.005, P = 0.24). CONCLUSION: In this survey, we found high
      work satisfaction among Scandinavian anaesthesiologists, with no difference
      between coffee and non-coffee drinkers.

PMID- 30238964
TI  - A multiple-group confirmatory factor analysis of teacher perceptions of social
      and emotional learning in rural Malawi.
AB  - BACKGROUND: Social and emotional learning (SEL) positively impacts children's
      school achievement and adult productivity. Successful implementation of SEL
      relies on teachers' pedagogical beliefs and practices. AIMS: We examined whether
      the Teachers' SEL Belief Scale designed in the United States is adoptable in low
      income countries such as Malawi in response to a growing interest in teacher
      practices in SEL but a lack of research instruments in these countries. SAMPLES:
      The data used in this study were from 432 teachers working in 34 randomly
      selected primary schools in Zomba, a rural district in Malawi. METHODS: We used
      multiple-group confirmatory factory analysis to investigate the factor structure
      and the invariance of the adapted scale across teachers with different
      characteristics such as gender and training experience in SEL. When invariant, we
      compared group mean differences among teachers in our sample by gender and
      training experience. RESULTS: We found that the Teachers' SEL Belief Scale
      measured a similar construct of pedagogical perceptions of SEL among the sampled
      teachers, and it functioned equivalently across teachers with different genders
      and training experiences. Female teachers had lower perceived institutional
      support for SEL instruction compared to male teachers. Untrained teachers had
      lower levels of pedagogical comfort as well as perceived support for SEL compared
      to trained teachers. CONCLUSIONS: Our findings validate the adaptability of the
      Teachers' SEL Belief Scale in low-income contexts such as Malawi. We did not find
      evidence of systematic bias relative to group membership. In addition,
      significantly lower pedagogical comfort and institutional support among female
      and untrained teachers suggest areas for policy intervention to improve teacher
      performance in SEL in Malawi.

PMID- 30238965
TI  - Dabigatran Etexilate and Digoxin: Comparison as Clinical Probe Substrates for
      Evaluation of P-gp Inhibition.

PMID- 30238966
TI  - Personal values and immigrant group appraisal as predictors of voluntary contact
      with immigrants among majority students in Israel.
AB  - What predicts whether young people will establish contacts with immigrants?
      Students are at a pivotal point in which the campus environment can enable
      substantial contact with immigrants, and where world views and behavioural
      patterns are formed which can follow through their adult lives. Through a value
      attitude-behavior paradigm we examine a conceptual model in which appraisal of an
      immigrant group as a threat and/or benefit to the host society mediates the
      relationship between personal values and contact. Findings among 252 students in
      Israel showed that (1) threat/benefit appraisal of immigrants predicted voluntary
      contact; (2) personal values of self-direction and hedonism directly predicted
      voluntary contact; and (3) Threat/benefit appraisal mediated the relationship
      between self-direction and power and contact. Results suggest that increasing
      awareness of benefits of immigrants can promote positive inter-group relations.

PMID- 30238968
TI  - Teachers' attitudes towards ethnic minority students: Effects of schools'
      cultural diversity.
AB  - BACKGROUND: Research exploring mechanisms driving inequalities in school systems
      has found that biased teacher judgements contribute to observed disadvantages for
      ethnic minority students. Teacher judgements may be driven by explicit and
      implicit attitudes. AIMS: The current research explored the effect of cultural
      diversity at schools (actual or imagined) on teachers' attitudes towards ethnic
      minority students. SAMPLES: One hundred and five preservice teachers (90 female)
      with a mean age of 26.20 years (teaching experience: 57.55 weeks) participated in
      Study 1. Two hundred and thirty-one teachers (159 female) with a mean age of
      41.00 years (teaching experience: 12.92 years) participated in Study 2. METHOD:
      Cultural diversity was operationalized via a fictive description of a school
      (Study 1) or via the actual proportion of ethnic minority students at the school
      (Study 2). An Implicit Association Test assessed implicit attitudes towards
      ethnic minority students. Explicit attitudes were assessed via questionnaire.
      RESULTS: Preservice teachers imagining a more culturally diverse school held more
      negative implicit attitudes towards ethnic minority students than those imagining
      a less diverse school. In contrast, in-service teachers actually working in more
      diverse schools held less negative implicit attitudes towards minority students.
      Preservice teachers associated teaching in culturally diverse schools with
      increased effort, whereas in-service teachers actually working in culturally
      diverse schools reported more enthusiasm towards teaching ethnic minority
      students. CONCLUSIONS: This research shows the challenge and the negative
      stereotypes preservice teachers associate with culturally diverse schools, while
      in-service teachers' negative associations may be buffered by the actual
      experience of working with ethnic minority students.

PMID- 30238967
TI  - Neurodevelopmental phenotype caused by a de novo PTPN4 single nucleotide variant
      disrupting protein localization in neuronal dendritic spines.
AB  - Protein tyrosine phosphatase non-receptor type 4 (PTPN4) encodes non-receptor
      protein tyrosine phosphatase implicated in synaptic plasticity and innate immune
      response. The only report of PTPN4-associated disease described a
      neurodevelopmental disorder associated with a whole gene deletion. We describe a
      child with developmental delay, autistic features, hypotonia, increased
      immunoglobulin E and dental problems with a novel mosaic de novo variant in PTPN4
      (hg19 chr2:g.120620188 T > C, NM_002830.3:p.[Leu72Ser]/c.215T>C) located in
      domain that controls protein subcellular distribution. Studies in mouse
      hippocampal neurons transfected with non-mutated or mutated human PTPN4 showed
      that despite their similar expression in neurons the mutated protein was absent
      from dendritic spines. Next, we studied patient's primary blood mononuclear
      cells' response to lipopolysaccharide stimulation and found no difference from
      control in phosphorylation of TBK1 and IRF3 (involved in Toll-like receptor 4
      signaling) and induction of cytokines' messenger RNA. We conclude that the PTPN4
      p.(Leu72Ser) variant is a likely cause of neurodevelopmental symptoms of our
      proband whereas its role in immune dysfunction requires further studies.

PMID- 30238969
TI  - Fluid deficits during prolonged overnight fasting in young healthy adults.
AB  - BACKGROUND: Overnight fasting is often prolonged before scheduled surgery, and
      the extent of perioperative fluid replacement may influence outcome. In clinical
      practice, basic requirements are estimated at 1.2-2.0 mL.kg-1 .h-1 , but there is
      little contemporary clinical data on what deficits result from complete fasting.
      This prospective preclinical study was designed to determine total fluid loss
      during overnight fasting, prolonged during daytime. METHODS: Twenty (10 female)
      healthy adult volunteers, aged 24 (range 21-46) years, fasted from 22:00 until
      16:00, and had their body weight and urine output measured at predefined time
      intervals. RESULTS: The median (interquartile range) fluid deficits were 0.82
      (0.73-1.00) kg, corresponding to 1.26 (1.11-1.41) g.kg-1 .h-1 for the initial
      overnight fasting period, 0.59 (0.40-0.70) kg and 0.99 (0.83-1.31) g.kg-1 .h-1
      for the consecutive daytime period, and 1.47 (1.27-1.64) kg and 1.19 (1.05-1.28)
      g.kg-1 .h-1 for the total period of fasting. Urine output accounted for 52% of
      total weight loss and was 36% of the baseline hourly level during the last four
      hour period of fasting. CONCLUSIONS: Ten hours of overnight fasting in young
      adults induces fluid deficits at the lower limit of estimated intervals referred
      to in clinical practice, and hourly weight loss gradually decreases further
      during prolonged daytime fasting. These findings indicate that current routine
      procedures do slightly overestimate fluid deficits resulting from prolonged
      fasting in perioperative clinical practice.

PMID- 30238970
TI  - Frailty and Delirium in Older Adults: A Systematic Review and Meta-Analysis of
      the Literature.
AB  - OBJECTIVES: To evaluate the relationship between frailty and delirium. DESIGN:
      Systematic review and meta-analysis. SETTING: MEDLINE, EMBASE, PubMed, Scopus,
      Web of Science, and Google Scholar databases were searched for articles on
      frailty and delirium published on or before October 31, 2017. PARTICIPANTS:
      Individuals aged 65 and older. MEASUREMENTS: Two authors independently reviewed
      all English-language citations, extracted relevant data, and assessed studies for
      potential bias. Articles involving pediatric or neurosurgical populations,
      alcohol or substance abuse, psychiatric illness, head trauma, or stroke, as well
      as review articles, letters, and case reports were excluded. Studies underwent
      qualitative or quantitative analysis according to specified criteria. Using a
      random-effects or fixed-effects model, relative risk (RR) was calculated for the
      effect of frailty as a predictor of subsequent delirium. Heterogeneity was tested
      using Q and I2 statistics. RESULTS: We identified 1,626 articles from our initial
      search, of which 20 fulfilled the selection criteria (N=5,541 participants, mean
      age 77.8). Eight studies were eligible for meta-analysis, showing a significant
      association between Q2 frailty and subsequent delirium (RR = 2.19, 95% confidence
      interval = 1.65-2.91). There was low variability among studies in the measures of
      association between frailty and delirium (I2 2.24, p-value Q-statistic = .41) but
      high heterogeneity in the methods used to assess the two conditions. CONCLUSION:
      This systematic review and meta-analysis supports the existence of an independent
      relationship between frailty and delirium, although there is notable
      methodological heterogeneity between the methods used to assess the 2 conditions.
      Future studies are needed to better delineate the dynamics between these
      syndromes.

PMID- 30238971
TI  - Protection From Environmental Skin Damage With Topical Antioxidants.
AB  - Skin is an efficient protective barrier armed with an intricate network of
      antioxidants. External environmental stress diminishes and sometimes overwhelms
      these innate protective mechanisms; aging slows their efficacy. Topical
      antioxidants enhance natural endogenous defenses to create an indwelling
      reservoir for sustained protection with far higher concentrations than possible
      with oral intake. The challenge is creating formulations of these labile
      molecules that are stable, active, and can be effectively absorbed transdermally
      to deliver high concentrations.

PMID- 30238972
TI  - Cancer incidence in older adults in selected regions of sub-Saharan Africa, 2008
      2012.
AB  - Although the countries of Sub-Sharan Africa represent among the most rapidly
      growing and aging populations worldwide, no previous studies have examined the
      cancer patterns in older adults in the region as a means to inform cancer
      policies. Using data from Cancer Incidence in Five Continents, we describe recent
      patterns and trends in incidence rates for the major cancer sites in adults aged
      >=60 years and in people aged 0-59 for comparison in four selected population
      based cancer registries in Kenya (Nairobi), the Republic of South Africa (Eastern
      Cape Province), Uganda (Kyadondo country), and Zimbabwe (Harare blacks). Over the
      period 2008-2012, almost 9,000 new cancer cases were registered in older adults
      in the four populations, representing one-third of all cancer cases. Prostate and
      oesophageal cancers were the leading cancer sites in older males, while breast,
      cervical and oesophageal cancers were the most common among older females. Among
      younger people, Kaposi sarcoma and non-Hodgkin lymphoma were common. Over the
      past 20 years, incidence rates among older adults have increased in both sexes in
      Uganda and Zimbabwe while rates have stabilized among the younger age group.
      Among older adults, the largest rate increase was observed for breast cancer
      (estimated annual percentage change: 5% in each country) in females and for
      prostate cancer (6-7%) in males. Due to the specific needs of older adults,
      tailored considerations should be given to geriatric oncology when developing,
      funding and implementing national and regional cancer programmes. This article is
      protected by copyright. All rights reserved.

PMID- 30238973
TI  - Second primary cancers in non-Hodgkin lymphoma: Bidirectional analyses suggesting
      role for immune dysfunction.
AB  - Second primary cancers (SPCs) account for an increasing proportion of all cancer
      diagnoses. It is unlikely that prior therapy is solely responsible for SPC risk.
      To investigate risk of SPC after diagnosis of non-Hodgkin lymphoma (NHL) and 10
      of its subtypes we conducted a novel bidirectional analysis, SPCs after NHL and
      NHL as SPC. Using the Swedish Family-Cancer Database, we identified 19,833
      individuals with primary NHL diagnosed between 1993 and 2015. We calculated
      relative risks (RRs) of SPCs in NHL survivors and, for bi-directional analysis,
      risk of NHL as SPC. The overall RRs were significantly bidirectionally increased
      for NHL and 7 cancers. After diagnosis of NHL risks were increased for upper
      aerodigestive tract (RR = 1.96), colorectal (1.35), kidney (3.10), bladder (1.54)
      and squamous cell skin cancer (SCC) (4.12), melanoma (1.98) and Hodgkin lymphoma
      (9.38). The concordance between RRs for each bidirectional association between
      NHL and 31 different cancers was highly significant (r = 0.86, p < 0.0001).
      Melanoma was bidirectionally associated with all 10 subtypes of NHL. The observed
      bidirectional associations between NHL and cancer suggest that therapy-related
      carcinogenic mechanisms cannot solely explain the findings. Considering that skin
      SCC and melanoma are usually treated by surgery and that these cancers and NHL
      are most responsive of any cancer to immune suppression, the consistent
      bidirectional results provide population-level evidence that immune suppressed
      state is a key underlying mechanism in the context of SPCs. Furthermore, the
      quantified risks for NHL subtypes have direct clinical application in the
      management of NHL patients.

PMID- 30238974
TI  - Constructing the Apparent Geological Model by Fusing Surface Resistivity Survey
      and Borehole Records.
AB  - We constructed an apparent geological model with resistivity data from surface
      resistivity surveys. We developed a data fusion approach by integrating dense
      electrical resistivity measurements collected with Schlumberger arrays and
      wellbore logs. This approach includes an optimization algorithm and a
      geostatistic interpolation method. We first generated an apparent formation
      factor model from the surface resistivity measurements and groundwater
      resistivity records with an inverse distance method. We then converted the model
      into a geology model with the optimized judgment criteria from the algorithms
      relating the apparent formation factors to the borehole geology. We also employed
      a non-parametric bootstrap method to analyze the uncertainty of the predicted
      sediment types, and the predictive uncertainties of clay, gravel, and sand were
      less than 5%. Overall, our model is capable of capturing the spatial features of
      the sediment types. More importantly, this approach can be arranged in a self
      updated sequence to enable adjustments to the model to accommodate newly
      collected core records or geophysical data. This approach yields a more detailed
      apparent geological model for use in future groundwater simulations, which is of
      benefit to multi-discipline studies. This article is protected by copyright. All
      rights reserved.

PMID- 30238976
TI  - Effect of specially designed oral health preventive programme on oral health of
      visually impaired children: use of audio and tactile aids.
AB  - INTRODUCTION: Contemporary methods of teaching oral hygiene for the removal of
      dental plaque are not beneficial for visually impaired children, who depend on
      tactile sensations and hearing for learning. The present study was conducted to
      educate and motivate visually impaired children to maintain their oral health
      using specially designed methods that are easy for these children to understand.
      Additionally, the study evaluated the effectiveness of these methods over a 6
      month period. METHODOLOGY: The investigation was done on 148 visually impaired
      children who were residents of two institutes for the visually impaired. The
      efficacy of a specially designed oral health education programme and two
      different motivational techniques utilising tactile (Group I: braille + plastic
      models) or auditory sensations (Group II: audio story + JAWS(r) , i.e. Job Access
      With Speech) was evaluated over 6 months based on the children's plaque and
      gingival scores. RESULTS: Significant improvement in mean plaque and gingival
      scores was evident in both the groups at the 6-month evaluation, validating the
      effectiveness of both the programmes. In Group I, the mean plaque score decreased
      from 1.34 +/- 0.29 at baseline to 1.09 +/- 0.26 at 3 months, with a further
      decrease to 1.04 +/- 0.31 at 6 months post-implementation (P < 0.01). The mean
      plaque score in Group II decreased from 1.24 +/- 0.47 at baseline to 1.15 +/-
      0.15 at 3 months (P = 0.12), and further to 1.10 +/- 0.17 at 6 months (P < 0.01)
      post-implementation of the educational programme. At baseline, 87.8% of the
      children in Group I had moderate gingivitis, whereas 52.7% of the children in
      Group II belonged to the mild category. At the end of 6 months, 52.7% of the
      children in Group I were in the mild category, and 62.2% children in Group II
      were in the moderate category. CONCLUSION: Tactile and auditory measures were
      found to be effective in educating and motivating visually impaired children
      regarding maintenance of oral hygiene.

PMID- 30238975
TI  - Size matters: Dissecting key parameters for panel-based tumor mutational burden
      analysis.
AB  - Tumor mutational burden (TMB) represents a new determinant of clinical benefit
      from immune checkpoint blockade that identifies responders independent of PD-L1
      expression levels and is currently being explored in clinical trials. Although
      TMB can be measured directly by comprehensive genomic approaches such as whole
      genome and exome sequencing, broad availability, short turnaround times, costs
      and amenability to formalin-fixed and paraffin-embedded tissue support the use of
      gene panel sequencing for approximating TMB in routine diagnostics. However, data
      on the parameters influencing panel-based TMB estimation are limited. Here, we
      report an extensive in silico analysis of the TCGA data set that simulates
      various panel sizes and compositions. We demonstrate that panel size is a
      critical parameter that influences confidence intervals (CIs) and cutoff values
      as well as important test parameters including sensitivity, specificity, and
      positive predictive value. Moreover, we evaluate the Illumina TSO500 panel, which
      will be made available for TMB estimation, and propose dynamic, entity-specific
      cutoff values based on current clinical trial data. Optimizing the cost-benefit
      ratio, our data suggest that panels between 1.5 and 3 Mbp are ideally suited to
      estimate TMB with small CIs, whereas smaller panels tend to deliver imprecise TMB
      estimates for low to moderate TMB (0-30 muts/Mbp), connected with insufficient
      separation of hypermutated tumors from non-hypermutated tumors.

PMID- 30238977
TI  - Identifying Children with Special Health Care Needs Using Medicaid Data in New
      York State Medicaid Managed Care.
AB  - OBJECTIVE: The ability to identify children with special health care needs
      (CSHCN) is crucial to evaluate disparities in the quality of health care for
      children in Medicaid Managed Care. We developed and assessed the accuracy of a
      new method to classify CSHCN. DATA SOURCES: Secondary data analysis was conducted
      using NYS Medicaid administrative data and the Children with Chronic Conditions
      Screener (CCC Screener). STUDY DESIGN: This study included 5,907 NYS Medicaid
      beneficiaries (17 years old or younger) whose parents completed the CCC Screener
      in 2014. Medicaid administrative data were used to create a risk score to assess
      the risk of special needs, and a cut point was identified to differentiate
      between children with versus without special needs. Diagnostic accuracy of the
      method was assessed using sensitivity and specificity analyses. PRINCIPAL
      FINDINGS: Applying the CCC Screener as the "gold standard," the risk score
      correctly classified the majority of CSHCN as positive (sensitivity = 75 percent)
      and the majority of the children without special needs as negative (specificity =
      79 percent). This method demonstrated decent diagnostic ability (AUC = 0.77).
      CONCLUSIONS: Our method can identify CSHCN in the NYS Medicaid Managed Care
      population and will help the State monitor the quality of care for this
      vulnerable population.

PMID- 30238978
TI  - Melatonin and cancer: From the promotion of genomic stability to use in cancer
      treatment.
AB  - Cancer remains among the most challenging human diseases. Several lines of
      evidence suggest that carcinogenesis is a complex process that is initiated by
      DNA damage. Exposure to clastogenic agents such as heavy metals, ionizing
      radiation (IR), and chemotherapy drugs may cause chronic mutations in the genomic
      material, leading to a phenomenon named genomic instability. Evidence suggests
      that genomic instability is responsible for cancer incidence after exposure to
      carcinogenic agents, and increases the risk of secondary cancers following
      treatment with radiotherapy or chemotherapy. Melatonin as the main product of the
      pineal gland is a promising hormone for preventing cancer and improving cancer
      treatment. Melatonin can directly neutralize toxic free radicals more efficiently
      compared with other classical antioxidants. In addition, melatonin is able to
      regulate the reduction/oxidation (redox) system in stress conditions. Through
      regulation of mitochondrial nction and inhibition of pro-oxidant enzymes,
      melatonin suppresses chronic oxidative stress. Moreover, melatonin potently
      stimulates DNA damage responses that increase the tolerance of normal tissues to
      toxic effect of IR and may reduce the risk of genomic instability in patients who
      undergo radiotherapy. Through these mechanisms, melatonin attenuates several side
      effects of radiotherapy and chemotherapy. Interestingly, melatonin has shown some
      synergistic properties with IR and chemotherapy, which is distinct from classical
      antioxidants that are mainly used for the alleviation of adverse events of
      radiotherapy and chemotherapy. In this review, we describe the anticarcinogenic
      effects of melatonin and also its possible application in clinical oncology.

PMID- 30238979
TI  - Exercise rescues the immune response fine-tuned impaired by peroxisome
      proliferator-activated receptors gamma deletion in macrophages.
AB  - BACKGROUND: Exercise is a powerful tool for prevention and treatment of many
      conditions related to the cardiovascular system and also chronic low-grade
      inflammation. Peroxisome proliferator-activated receptors gamma (PPARgamma)
      exerts an import role on the regulation of metabolic profile and subsequent
      inflammatory response, especially in macrophages. PURPOSE: To investigate the
      effects of 8-week moderate-exercise training on metabolic and inflammatory
      parameters in mice with PPARgamma deficiency in myeloid cells. METHODS: Twelve
      week old mice bearing PPARgamma deletion exclusively in myeloid cells
      (PPARgammalox/lox Lys Cre -/+ , knockout [KO]) and littermate controls
      (PPARgammalox/lox Lys Cre -/- , wild type [WT]) were submitted to 8-week exercise
      training (treadmill running at moderate intensity, 5 days/week). Animals were
      evaluated for food intake, glucose homeostasis, serum metabolites, adipose tissue
      and peritoneal macrophage inflammation, and basal and stimulated cytokine
      secretion. RESULTS: Exercise protocol did not improve glucose metabolism or
      adiponectin concentrations in serum of KO mice. Moreover, the absence of
      PPARgamma in macrophages exacerbated the proinflammatory profile in sedentary
      mice. Peritoneal cultured cells had higher tumor necrosis factor-alpha (TNF
      alpha) secretion in nonstimulated and lipopolysaccharide (LPS)-stimulated
      conditions and higher Toll-4 receptor (TLR4) gene expression under LPS stimulus.
      Trained mice showed reduced TNF-alpha content in adipose tissue independently of
      the genotype. M2 polarization ability was impaired in KO peritoneal macrophages
      after exercise training, while adipose tissue-associated macrophages did not
      present any effect by PPARgamma ablation. CONCLUSION: Overall, PPARgamma seems
      necessary to maintain macrophages appropriate response to inflammatory stimulus
      and macrophage polarization, affecting also whole body lipid metabolism and
      adiponectin profile. Exercise training showed as an efficient mechanism to
      restore the immune response impaired by PPARgamma deletion in macrophages.

PMID- 30238980
TI  - Ephrin A1 promotes proliferation of bovine endometrial cells with abundant
      expression of proliferating cell nuclear antigen and cyclin D1 changing the cell
      population at each stage of the cell cycle.
AB  - Ephrin A1 has a role in a variety of biological events, including cell
      proliferation, differentiation, migration, and angiogenesis. Ephrin A1 expression
      is abundant in trophoblasts and endometrial cells during the implantation period;
      however, its intracellular activities have not yet been reported in bovine
      endometrial (BEND) epithelial cells. The aim of this study was to identify the
      functional role of ephrin A1 in BEND cells, which have served as a good model
      system for investigating the regulation of signal transduction following
      treatment with interferon-tau (IFNT) in vitro. Supplementation of ephrin A1 to
      BEND cells increased cell proliferation and increased levels of proliferating
      cell nuclear antigen and cyclin D1 protein in BEND cell nuclei. To investigate
      intracellular mechanisms regulated by ephrin A1, we performed Western blot
      analysis focused on mitogen-activated protein kinase (MAPK) and phosphoinositide
      3-kinase (PI3K) signaling, which are significantly involved in the successful
      maintenance of pregnancy. Ephrin A1 dose-dependently increased phosphorylation of
      extracellular signal-regulated kinases (ERK)1/2, c-Jun N-terminal kinases (JNK),
      P38, protein kinase B (AKT), P70S6K, S6, and cyclin D1, and the activated
      proteins were suppressed by pharmacological inhibitors including wortmannin (a
      PI3K inhibitor), U0126 (an ERK1/2 inhibitor), and SP600125 (a JNK inhibitor).
      Among ephrin A1 receptors, abundant expression of EPHA2 and EPHA4 messenger RNA
      was detected in BEND cells by reverse transcription polymerase chain reaction
      analysis. Furthermore, tunicamycin-induced endoplasmic reticulum (ER) stress was
      inactivated by ephrin A1 treatment of BEND cells. Our findings suggest that
      ephrin A1 promotes the development of BEND cells and likely enhances uterine
      capacity and maintenance of pregnancy by activating MAPK and PI3K signaling
      cascades and by restoring ER stress.

PMID- 30238981
TI  - Laminar shear stress-provoked cytoskeletal changes are mediated by epigenetic
      reprogramming of TIMP1 in human primary smooth muscle cells.
AB  - Whereas endothelial responses to shear stress are well-characterized, the cell
      physiological effects of shear stress in smooth muscle cells (SMCs) remain
      largely obscure. As SMCs are directly challenged by shear stress after
      endothelial denuding injury following procedures such as angioplasty or
      endarterectomy, characterization of these responses represents an important
      scientific question. Hence we decided to contrast cytoskeletal reorganization,
      epigenetic reprogramming, signaling transduction, and changes in miRNA (miRs)
      profiles in primary human aortic smooth muscle cells (AoSMCs) between unstressed
      cells and cells exposed to shear stress. We observed that shear stress-provoked
      reorganization of the actin cytoskeleton in an apparently Cofilin-dependent
      fashion and which related to altered integrin signaling, apparently caused by
      remodeling of the extracellular matrix. The latter appeared a downstream effect
      of increased expression of matrix metalloproteinases and downregulation of tissue
      metalloproteinase inhibitor 1 (TIMP1) protein levels. In turn, these effects
      related to shear stress-provoked changes in expression and nuclear localization
      of the epigenetic regulators demethylases TET1, TET2, DNMT1, DNMT3A and DNMT3B,
      HDAC6, and SIRT1. Accordingly, TIMP1 promotor CpG hypomethylation was a prominent
      effect, and resulted in a significant increase in TIMP1 transcription, which may
      also have related increased expression of miRs involved in modulating TIMP1
      translation. Thus epigenetic-reprogramming of TIMP1 emerges as critical element
      in smooth muscle responses to mechanical signals and as epigenetic machinery is
      amendable to pharmacological manipulation, this pathway may have important
      clinical consequences.

PMID- 30238982
TI  - Upregulation of lncRNA DGCR5 correlates with better prognosis and inhibits
      bladder cancer progression via transcriptionally facilitating P21 expression.
AB  - Mounting studies show that long noncoding RNAs (lncRNAs) could affect human
      cancer progression, including bladder cancer (BCa). LncRNA DiGeorge syndrome
      critical region gene 5 (DGCR5) has been proven to be involved in lung cancer,
      pancreatic ductal adenocarcinoma, and hepatocellular carcinoma. However, the
      function of DGCR5 in BCa remains largely unknown. Here, we found that DGCR5
      expression was significantly downregulated in BCa tissues compared with adjacent
      normal tissues. Higher expression of DGCR5 predicted higher survival rate in BCa
      patients. Functional experiments indicated that DGCR5 overexpression markedly
      inhibited that proliferation, colony formation, and cell-cycle progression in BCa
      cells. Furthermore, ectopic expression of DGCR5 led to decreased BCa cell
      migration, invasion, and epithelial-mesenchymal transition while promoting
      apoptosis. In vivo xenograft assay also illustrated that DGCR5 overexpression
      inhibited BCa growth. In the mechanism, we found that DGCR5 interacted with AT
      rich interaction domain 1A (ARID1A), a chromatin remodeling protein, to promote
      P21 transcription. Knockdown of P21 could significantly rescue the suppressed
      proliferation, migration, and invasion of BCa cells by DGCR5 overexpression. In
      summary, our study demonstrated that DGCR5 transcriptionally promotes P21
      expression to suppress BCa progression.

PMID- 30238983
TI  - Novel therapies and preventative strategies for primary and recurrent Clostridium
      difficile infections.
AB  - Clostridium difficile is the leading infectious cause of antibiotic-associated
      diarrhea and colitis. C. difficile infection (CDI) places a heavy burden on the
      healthcare system, with nearly half a million infections yearly and an
      approximate 20% recurrence risk after successful initial therapy. The high
      incidence has driven new research on improved prevention such as the emerging use
      of probiotics, intestinal microbiome manipulation during antibiotic therapies,
      vaccinations, and newer antibiotics that reduce the disruption of the intestinal
      microbiome. While the treatment of acute C. difficile is effective in most
      patients, it can be further optimized by adjuvant therapies that improve the
      initial treatment success and decrease the risk of subsequent recurrence.
      Finally, the high risk of recurrence has led to multiple emerging therapies that
      target toxin activity, recovery of the intestinal microbial community, and
      elimination of latent C. difficile in the intestine. In summary, CDIs illustrate
      the complex interaction among host physiology, microbial community, and pathogen
      that requires specific therapies to address each of the factors leading to
      primary infection and recurrence.

PMID- 30238984
TI  - Hypoxia induces ZEB2 in podocytes: Implications in the pathogenesis of
      proteinuria.
AB  - The glomerular filtration barrier (GFB) plays a critical role in ensuing protein
      free urine. The integrity of the GFB is compromised during hypoxia that prevails
      during extreme physiological conditions. However, the mechanism by which
      glomerular permselectivity is compromised during hypoxia remains enigmatic. Rats
      exposed to hypoxia showed a decreased glomerular filtration rate, podocyte foot
      processes effacement, and proteinuria. Accumulation of hypoxia-inducible factor
      1alpha (HIF1alpha) in podocytes resulted in elevated expression of zinc finger E
      box binding homeobox 2 (ZEB2) and decreased expression of E- and P-cadherin. We
      also demonstrated that HIF1alpha binds to hypoxia response element localized in
      the ZEB2 promoter. Furthermore, HIF1alpha also induced the expression of ZEB2
      natural antisense transcript, which is known to increase the efficiency of ZEB2
      translation. Ectopic expression of ZEB2 induced loss of E- and P-cadherin and is
      associated with enhanced motility of podocytes during hypoxic conditions. ZEB2
      knockdown abrogated hypoxia-induced decrease in podocyte permselectivity. This
      study suggests that hypoxia leads to activation of HIF1alpha-ZEB2 axis, resulting
      in podocyte injury and poor renal outcome.

PMID- 30238985
TI  - Stromal vascular fraction cells plus sustained release VEGF/Ang-1-PLGA
      microspheres improve fat graft survival in mice.
AB  - Autologous fat transplantation is increasingly applied in plastic and
      reconstructive surgery. Stromal vascular fraction cells (SVFs) combined with
      angiogenic factors, such as VEGF (vascular endothelial growth factor A) and Ang-1
      (angiogenin-1), can improve angiogenesis, which is a critical factor for graft
      survival. However, direct transplant with such a mixture is insufficient owing to
      the short half-life of angiogenic factors. In this study, we evaluated whether a
      double sustained release system of VEGF/ANG-1-PLGA (poly (lactic-co-glycolic
      acid)) microspheres plus SVFs can improve angiogenesis and graft survival after
      autologous fat transplantation. VEGF/ANG-1-PLGA-sustained release microspheres
      were fabricated by a modified double emulsion-solvent evaporation technique.
      Human aspirated fat was mixed with SVF suspension plus VEGF/ANG-1 sustained
      release microspheres (Group C), SVF suspension (Group B) alone, or Dulbecco's
      modified Eagle's medium as the control (Group A). Eighteen immunocompromised nude
      mice were injected with these three mixtures subcutaneously at random positions.
      After 8 weeks, the mean volume of grafts was greater in the SVFs plus VEGF/ANG-1
      PLGA group than in the control and SVFs groups (1.08 +/- 0.069 ml vs. 0.62 +/-
      0.036 ml, and 0.83 +/- 0.059 ml, respectively). Histological assessments showed
      that lower fibrosis, but greater microvascular density in the SVFs plus VEGF/ANG
      1-PLGA group than in the other groups, though the SVFs group also had an
      appropriate capillary density and reduced fibrosis. Our findings indicate that
      SVFs plus VEGF/ANG-1-PLGA-sustained release microspheres can improve angiogenesis
      and graft survival after autologous fat transplantation.

PMID- 30238986
TI  - The genetic factors contributing to hypospadias and their clinical utility in its
      diagnosis.
AB  - Hypospadias is among the most common congenital malformations in male neonates.
      It results from abnormal penile and urethral development, but is a multifactorial
      disorder that is highly heterogeneous, with several genetic and environmental
      determinants. Monogenic and chromosomal abnormalities are present in
      approximately 30% of cases, although the genetic factors contributing to
      hypospadias remain unknown in 70% of cases. While defects in androgen synthesis
      can lead to this malformation, mutational analyses have shown several genes, such
      as sonic hedgehog, fibroblast growth factors, bone morphogenetic proteins,
      homeobox genes, and the Wnt family, are involved in the normal development of
      male external genitalia. Mutations in the genes of penile development (e.g., HOX,
      FGF, Shh) and testicular determination (e.g., WT1, SRY), luteinizing hormone
      receptor, and androgen receptor have also been proposed to be implicated in
      hypospadias. Here we review the recent advances in this field and discuss the
      potential genes that could determine the risk of hypospadias.

PMID- 30238987
TI  - A genetic variant in CDKN2A/2B locus was associated with poor prognosis in
      patients with esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer
      related death. Despite of extensive efforts in identifying valid cancer
      prognostic biomarkers, only a very small number of markers have been identified.
      Several genetic variants in the 9p21 region have been identified that are
      associated with the risk of multiple cancers. Here, we explored the association
      of two genetic variants in the 9p21 region, CDKN2A/B, rs10811661, and rs1333049
      for the first time in 273 subjects with, or without ESCC. We observed that the
      patients with ESCC had a higher frequency of a TT genotype for rs10811661 than
      individuals in the control group, and this polymorphism was also associated with
      tumor size. Moreover, a CC genotype for the rs1333049 polymorphism was associated
      with a reduced overall survival (OS) of patients with ESCC. In particular,
      patients with a CC (rs1333049) genotype had a significantly shorter OS (CC
      genotype: 34.5 +/- 8.9 months vs. CG+GG: 47.7 +/- 5.9 months; p value = 0.03). We
      have also shown the association of a novel genetic variant in CDKN2B gene with
      clinical outcome of patients with ESCC. Further investigations are warranted in a
      larger population to explore the value of emerging markers as a risk
      stratification marker in ESCC.

PMID- 30238988
TI  - Genetics and rheumatoid arthritis susceptibility in Iran.
AB  - Rheumatoid arthritis (RA) is an autoimmune disorder with a number of risk
      factors, including both genetic and environmental. A number of RA risk associated
      genomic loci has been identified. In this review, we summarize the association of
      genetic factors with RA reported in population studies in Iran. No significant
      association was found between the majority of genetic factors identified in other
      populations and risk for RA in the Iranian subjects. This conflicting result
      could be due to the ethnic differences and diversity that are present in Iran. We
      conclude that there is a need to investigate larger groups of Iranian subjects,
      encompassing different regions of Iran, to either prove or refute these initial
      findings.

PMID- 30238989
TI  - Molecular mechanisms involved in the protective effect of pituitary adenylate
      cyclase-activating polypeptide in an in vitro model of amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by the loss of upper and lower motor neurons. Based on
      transcriptional profiles of motor cortex samples, in a previous work, we were
      able to classify two subgroups of sporadic ALS (SALS) patients, named SALS1 and
      SALS2. A further meta-analysis study has revealed sixteen drug targets commonly
      deregulated in SALS2 and superoxide dismutase 1 (SOD1) G93A mice. The identified
      candidate drug targets included pituitary adenylate cyclase-activating
      polypeptide (PACAP), epidermal growth factor receptor (EGFR) and matrix
      metallopeptidase-2 (MMP-2). By using a motor neuron-like hybrid cell line (NSC
      34) expressing human SOD1 G93A as an in vitro model of ALS, here we investigated
      the functional correlation among these three genes. Our results have shown that
      PACAP increases cell viability following serum deprivation. This effect is
      induced through EGFR transactivation mediated by protein kinase A stimulation.
      Furthermore, EGFR phosphorylation activates mitogen-activated protein
      kinases/extracellular signal-regulated kinases 1 and 2 survival signaling pathway
      and increases MMP-2 expression, significantly reduced by serum starvation. These
      results suggest that a deeper characterization of mechanisms involved in
      PACAP/EGFR/MMP-2 axis activation in G93A SOD1 mutated neurons may allow
      identifying new targets for ALS therapy.

PMID- 30238990
TI  - Teeth-derived stem cells: A source for cell therapy.
AB  - Cell therapy is one of the important therapeutic approaches in the treatment of
      many diseases such as cancer, degenerative diseases, and cardiovascular diseases.
      Among various cell types, which could be used as cell therapies, stem cell
      therapy has emerged as powerful tools in the treatment of several diseases.
      Multipotent stem cells are one of the main classes of stem cells that could
      originate from different parts of the body such as bone marrow, adipose,
      placenta, and tooth. Among several types of multipotent stem cells, tooth-derived
      stem cells (TDSCs) are associated with special properties such as accessible,
      easy isolation, and low invasive, which have introduced them as a good source for
      using in the treatment of several diseases such as neural injuries, liver
      fibrosis, and Cohrn's disease. Here, we provided an overview of TDSCs particular
      stem cells from human exfoliated deciduous teeth and clinical application of
      them. Moreover, we highlighted molecular mechanisms involved in the regulation of
      dental stem cells fate.

PMID- 30238991
TI  - Identification of a novel cell cycle-related gene signature predicting survival
      in patients with gastric cancer.
AB  - Gastric cancer (GC) is one of the most fatal cancers in the world. Thousands of
      biomarkers have been explored that might be related to survival and prognosis via
      database mining. However, the prediction effect of single gene biomarkers is not
      specific enough. Increasing evidence suggests that gene signatures are emerging
      as a possible better alternative. We aimed to develop a novel gene signature to
      improve the prognosis prediction of GC. Using the messenger RNA (mRNA)-mining
      approach, we performed mRNA expression profiling in a large GC cohort (n = 375)
      from The Cancer Genome Atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA)
      was performed, and we recovered genes related to the G2/M checkpoint, which we
      identified with a Cox proportional regression model. We identified a set of five
      genes (MARCKS, CCNF, MAPK14, INCENP, and CHAF1A), which were significantly
      associated with overall survival (OS) in the test series. Based on this five-gene
      signature, the test series patients could be classified into high-risk or low
      risk subgroups. Multivariate Cox regression analysis indicated that the
      prognostic power of this five-gene signature was independent of clinical
      features. In conclusion, we developed a five-gene signature related to the cell
      cycle that can predict survival for GC. Our findings provide novel insight that
      is useful for understanding cell cycle mechanisms and for identifying patients
      with GC with poor prognoses.

PMID- 30238992
TI  - New elegant methods for maternal and fetal HPA-1a typing.

PMID- 30238993
TI  - And the beat goes on.

PMID- 30238994
TI  - Changes in size and composition of pigweed (Amaranthus hybridus L.) calcium
      oxalate crystals under CO2 starvation conditions.
AB  - The functional role(s) of plant calcium oxalate (CaOx) crystals are still poorly
      understood. Recently, it was shown that crystals function as dynamic carbon pools
      whose decomposition could provide CO2 to photosynthesis when stomata are closed
      (e.g. under drought conditions) and CO2 starvation conditions may be created
      within the mesophyll. This biochemical process, named as 'alarm photosynthesis',
      can become crucial for plant survival under adverse conditions. Here, we study
      crystal decomposition under controlled CO2 starvation conditions (either in the
      shoot or in the root) to obtain a better insight into the process of crystal
      formation and function. Hydroponically grown pigweed plants were kept in CO2 
      free air and/or CO2 -free nutrient medium for 9 days. Crystal volume was
      monitored daily, and carbon stable isotope composition (delta13 C) and Fourier
      transformation Raman spectra were obtained at the end of the experiment. A
      considerable reduction in the leaf crystal volume was observed in shoot-CO2 
      starved plants at the end of the experiment. The smallest crystals were isolated
      from the plants in which carbon was excluded from both the shoot and the root and
      contained potassium nitrate. Crystal delta13 C of CO2 -starved plants was altered
      in a predicted way. Specifically, it depended on the average calculated isotope
      fractionation of all carbon fixation processes considered to be contributing in
      each experimental treatment. The results of the present study confirmed the
      correlation between CO2 starvation conditions and the CaOx crystal decomposition.
      Inorganic carbon fixed in the root may represent a major carbon source for CaOx
      formation.

PMID- 30238995
TI  - Iturin A-like lipopeptides from Bacillus subtilis trigger apoptosis, paraptosis,
      and autophagy in Caco-2 cells.
AB  - This study revealed that iturin A-like lipopeptides produced by Bacillus
      subtillis induced both paraptosis and apoptosis in heterogeneous human epithelial
      colorectal adenocarcinoma (Caco-2) cells. Autophagy was simultaneously induced in
      Caco-2 cells treated with iturin A-like lipopeptides at the early stage and
      inhibited at the later stage. A western blot analysis showed that the
      lipopeptides induced apoptosis in Caco-2 cells via a mitochondrial-dependent
      pathway, as indicated by upregulated expression of the apoptotic genes bax and
      bad and downregulated expression of the antiapoptotic gene bcl-2. The induction
      of paraptosis in Caco-2 cells was indicated by the occurrence of many cytoplasmic
      vacuoles accompanied by endoplasmic reticulum (ER) dilatation and mitochondrial
      swelling and dysfunction. ER stress also occurred with significant increases in
      reactive oxygen species and Ca2+ levels in cells. Autophagy was detected by a
      transmission electron microscopy analysis and by upregulated expression of LC3-II
      and downregulated expression of LC3-I. The inhibition of autophagy at the later
      stage was shown by upregulated expression of p62. This study revealed the
      capability of iturin A-like B. subtilis lipopeptides to simultaneously execute
      antitumor potential via multiple pathways.

PMID- 30238996
TI  - Phenotypic plasticity to photon flux density of physiological, anatomical and
      growth traits in a modern Criollo cocoa clone.
AB  - Cocoa grows under shade, but some cultivars develop successfully in full
      sunlight. In order to characterize the response to photosynthetic photon flux
      density (PPFD) of a Modern Criollo cocoa clone, gas exchange, photochemical
      activity and leaf traits, and their relation to growth were measured in seedlings
      growing in a greenhouse at three different values of PPFD, as well as in adults
      in full sunlight and shade in the field. Plants showed changes in physiological,
      biochemical, and morpho-anatomical traits in response to the different light
      conditions, and in the phenotypic plasticity of these variables. Seedlings
      subjected to high PPFD in the greenhouse showed decreases in photosynthetic rate,
      apparent quantum yield of CO2 fixation and photochemical quenching, and increases
      in non-photochemical quenching, suggesting down-regulation of PSII. In contrast,
      trees under full sunlight in the field showed a marked reduction in maximum
      quantum yield of PSII, indicating photoinhibition and supporting that cocoa is a
      shade tolerant crop. Cocoa showed higher plasticity of physiological and
      biochemical variables than morpho-anatomical variables in response to PPFD.
      Effects of time under treatment in the greenhouse and plant age (greenhouse vs
      field) on plasticity were observed. The acclimation observed in some of the
      variables studied after 6 months in high light did not represent a particular
      advantage to seedlings, since relative growth rate was lower than in low- and
      medium-light seedlings.

PMID- 30238997
TI  - Ectopic expression of olfactory receptors and associated G-protein subunits in
      the head integument of the amphihaline migratory fish hilsa Tenualosa ilisha.
AB  - The chemosensory nature of the tissue from the dorsal surface of the head (also
      termed sensory pad; SP) of the amphihaline diadromous fish hilsa Tenualosa ilisha
      was investigated for odorant receptor (OR), olfactory marker protein (OMP) and G
      protein subunits (Galphas-olf, Galphaq, Galphao, Galphai3) through
      immunolocalization and immunoblotting techniques. The immunolocalization of OR,
      OMP and G-protein subunits showed clear expression of these proteins in the
      tissues of the SP. Robust expressions of these proteins in the SP were detected
      with immunoblot analysis. The strong expression of these proteins in the SP
      indicates that the tissues from this area in riverine T. ilisha may play
      significant role in chemosensing and signalling through ectopic expression of
      olfactory receptor proteins which are otherwise reported in olfactory organs in
      vertebrates. Being migratory in nature, ectopic expression of these receptors in
      T. ilisha probably helps them to prevent damage to epidermal tissues of the SP,
      or they may also utilize them as a chemo and mechanosensory tool to optimize
      chemo-communications during migration.

PMID- 30238998
TI  - Impact on physiology and malting quality of barley exposed to heat, drought and
      their combination during different growth stages under controlled environment.
AB  - Drought and heat stress are two major abiotic stresses that tend to co-occur in
      nature. Recent climate change models predict that the frequency and duration of
      periods of high temperatures and moisture-deficits are on the rise and can be
      detrimental to crop production and hence a serious threat for global food
      security. In this study we examined the impact of short-term heat, drought and
      combined heat and drought stress on four barley varieties. These stresses were
      applied during vegetative stage or during heading stages. The impact on root and
      shoot biomass as well as seed yields were analyzed. This study demonstrated that
      sensitivity to combined stress was generally greater than heat or drought
      individually, and greater when imposed at heading than at the vegetative stages.
      Micromalted seeds collected from plants stressed during heading showed
      differences in malt extract, beta-glucan content and percent soluble protein.
      Screening barley germplasm during heading stage is recommended to identify novel
      sources of tolerance to combined stress. Apart from seed yield, assessing the
      seed quality traits of concern for the stakeholders and/or consumers should be an
      integral part of breeding programs for developing new barley varieties with
      improved heat and drought stress tolerance.

PMID- 30238999
TI  - Roles of plasma membrane proton ATPases AHA2 and AHA7 in normal growth of roots
      and root hairs in Arabidopsis thaliana.
AB  - Plasma membrane H+ -ATPase pumps build up the electrochemical H+ gradients that
      energize most other transport processes into and out of plant cells through
      channel proteins and secondary active carriers. In Arabidopsis thaliana, the
      AUTOINHIBITED PLASMA MEMBRANE H+ -ATPases AHA1, AHA2 and AHA7 are predominant in
      root epidermal cells. In contrast to other H+ -ATPases, we find that AHA7 is
      autoinhibited by a sequence present in the extracellular loop between
      transmembrane segments 7 and 8. Autoinhibition of pump activity was regulated by
      extracellular pH, suggesting negative feedback regulation of AHA7 during
      establishment of an H+ gradient. Due to genetic redundancy, it has proven
      difficult to test the role of AHA2 and AHA7, and mutant phenotypes have
      previously only been observed under nutrient stress conditions. Here, we
      investigated root and root hair growth under normal conditions in single and
      double mutants of AHA2 and AHA7. We find that AHA2 drives root cell expansion
      during growth but that, unexpectedly, restriction of root hair elongation is
      dependent on AHA2 and AHA7, with each having different roles in this process.

PMID- 30239000
TI  - Uptake and localization of fluorescently-labeled Karenia brevis metabolites in
      non-toxic marine microbial taxa.
AB  - Brevetoxin (PbTx) is a neurotoxic secondary metabolite of the dinoflagellate
      Karenia brevis. We used a novel, fluorescent BODIPY-labeled conjugate of
      brevetoxin congener PbTx-2 (B-PbTx) to track absorption of the metabolite into a
      variety of marine microbes. The labeled toxin was taken up and brightly
      fluoresced in lipid-rich regions of several marine microbes including diatoms and
      coccolithophores. The microzooplankton (20-200 MUm) tintinnid ciliate Favella sp.
      and the rotifer Brachionus rotundiformis also took up B-PbTx. Uptake and
      intracellular fluorescence of B-PbTx was weak or undetectable in phytoplankton
      species representative of dinoflagellates, cryptophytes, and cyanobacteria over
      the same (4 h) time course. The cellular fate of two additional BODIPY-conjugated
      K. brevis associated secondary metabolites, brevenal (B-Bn) and brevisin (B-Bs),
      were examined in all the species tested. All taxa exhibited minimal or
      undetectable fluorescence when exposed to the former conjugate, while most
      brightly fluoresced when treated with the latter. This is the first study to
      observe the uptake of fluorescently-tagged brevetoxin conjugates in non-toxic
      phytoplankton and zooplankton taxa, demonstrating their potential in
      investigating whether marine microbes can serve as a significant biological sink
      for algal toxins. The highly variable uptake of B-PbTx observed among taxa
      suggests some may play a more significant role than others in vectoring
      lipophilic toxins in the marine environment.

PMID- 30239001
TI  - Byproduct Generated During the Elaboration Process of Isotonic Beverage as a
      Natural Source of Bioactive Compounds.
AB  - : Agro-industrial byproducts are considered good sources of macronutrients and
      phytochemicals. Fruit and vegetable residues (FVR), obtained after the production
      of an isotonic beverage, have previously been characterized containing 80%
      insoluble dietary fibers from total fibers (48.4%), 26% available carbohydrates,
      9.5% proteins and 5% lipids. Nevertheless, fruit and vegetables provide
      phytochemicals which have been related to human health such as phenolic
      compounds. The loss of specific compounds over the production process is related
      to their partitioning between fruit and vegetables and byproducts. However,
      phenolic profile of FVR remains unknown. This work is focused on the evaluation
      of FVR as a natural source of these bioactive compounds. For this purpose,
      pressurized liquid extraction (PLE) has been proposed as extraction technique for
      recovering phenolic compounds from FVR. The experimental variables were
      temperature and percentage of solvent (ethanol and water). Phenolic compounds
      extracts were characterized by UPLC-ESI-Q-TOF-MS and a discussion about phenolic
      and macronutrient interactions was established. Globally, 88 compounds were
      tentatively identified: phenolic acids (28), flavonoids (32), and other
      polyphenols (28). The PLE conditions applied yielded different breaking matrix
      analyte interactions leading to an increase in the number of compounds. The
      highest phenolic acids content was achieved with high temperature while lower
      temperatures were more efficient in extracting flavonoid. By establishing the
      phenolics profile in food byproducts such as FVR, it is possible to more
      effectively apply these byproducts as nutraceutical, food or pharmaceutical
      ingredients. PRACTICAL APPLICATION: Flow diagram of bioactive compounds
      recovering from isotonic beverage byproduct is proposed using pressurized liquid
      extraction. The plant-bioactives mechanism relies on fruit and vegetable
      byproducts changes under different extraction conditions. The obtained extracts
      can most effectively be applied as nutraceuticals or as ingredients in food or
      pharmaceutical inputs.

PMID- 30239003
TI  - Renewal of extinguished operant behavior following changes in social context.
AB  - Renewal is the reoccurrence of previously extinguished behavior following a
      change in the context in which extinction was conducted. Despite an extensive
      body of research examining renewal, little is known about the role of social
      stimuli in renewal. The present experiments provided a novel examination of
      renewal of operant behavior by changing social stimuli across phases in an ABA
      renewal preparation. In both experiments, social stimuli were arranged by placing
      another rat in a second compartment of a divided operant chamber. In Experiment
      1, the presence of another rat defined the extinction context, whereas an empty
      second compartment defined the baseline and testing contexts. We reversed these
      contextual manipulations in Experiment 2 such that the presence of another rat
      defined the baseline and testing contexts and the second compartment was empty
      during extinction. Renewal of lever pressing occurred when the other rat was
      removed from the chamber in Experiment 1 and when the other rat was returned to
      the chamber in Experiment 2. Thus, social stimuli may function as contextual
      stimuli, and changes in social contexts may produce renewal of previously
      extinguished behavior.

PMID- 30239002
TI  - UBC-Nepal expedition: peripheral fatigue recovers faster in Sherpa than
      lowlanders at high altitude.
AB  - KEY POINTS: The reduced oxygen tension of high altitude compromises performance
      in lowlanders. In this environment, Sherpa display superior performance, but
      little is known on this issue. Sherpa present unique genotypic and phenotypic
      characteristics at the muscular level, which may enhance resistance to peripheral
      fatigue at high altitude compared to lowlanders. We studied the impact of gradual
      ascent and exposure to high altitude (5050 m) on peripheral fatigue in age
      matched lowlanders and Sherpa, using intermittent electrically-evoked
      contractions of the knee extensors. Peripheral fatigue (force loss) was lower in
      Sherpa during the first part of the protocol. Post-protocol, the rate of force
      development and contractile impulse recovered faster in Sherpa than in
      lowlanders. At any time, indices of muscle oxygenation were not different between
      groups. Muscle contractile properties in Sherpa, independent of muscle
      oxygenation, were less perturbed by non-volitional fatigue. Hence, elements
      within the contractile machinery contribute to the superior physical performance
      of Sherpa at high altitude. ABSTRACT: Altitude-related acclimatisation is
      characterised by marked muscular adaptations. Lowlanders and Sherpa differ in
      their muscular genotypic and phenotypic characteristics, which may influence
      peripheral fatigability at altitude. After gradual ascent to 5050 m, 12
      lowlanders and 10 age-matched Sherpa (32 +/- 10 vs. 31 +/- 11 years,
      respectively) underwent three bouts (separated by 15 s rest) of 75 intermittent
      electrically-evoked contractions (12 pulses at 15 Hz, 1.6 s between train onsets)
      of the dominant leg quadriceps, at the intensity which initially evoked 30% of
      maximal voluntary force. Trains were also delivered at minutes 1, 2 and 3 after
      the protocol to measure recovery. Tissue oxygenation index (TOI) and total
      haemoglobin (tHb) were quantified by a near-infrared spectroscopy probe secured
      over rectus femoris. Superficial femoral artery blood flow was recorded using
      ultrasonography, and delivery of oxygen was estimated (eDO2 ). At the end of bout
      1, peak force was greater in Sherpa than in lowlanders (91.5% vs. 84.5% baseline,
      respectively; P < 0.05). Peak rate of force development (pRFD), the first 200 ms
      of the contractile impulse (CI200 ), and half-relaxation time (HRT) recovered
      faster in Sherpa than in lowlanders (percentage of baseline at 1 min: pRFD: 89%
      vs. 74%; CI200 : 91% vs. 80%; HRT: 113% vs. 123%, respectively; P < 0.05).
      Vascular measures were pooled for lowlanders and Sherpa as they did not differ
      during fatigue or recovery (P < 0.05). Mid bout 3, TOI was decreased (90%
      baseline) whereas tHb was increased (109% baseline). After bout 3, eDO2 was
      markedly increased (1266% baseline). The skeletal muscle of Sherpa seemingly
      favours repeated force production at altitude for similar oxygen delivery
      compared to lowlanders.

PMID- 30239004
TI  - Cholesterol burden in the liver induces mitochondrial dynamic changes and
      resistance to apoptosis.
AB  - Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of
      histopathological changes ranging from non-inflammatory intracellular fat
      deposition to non-alcoholic steatohepatitis (NASH), which may progress into
      hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. Recent data suggest
      that impaired hepatic cholesterol homeostasis and its accumulation are relevant
      to the pathogenesis of NAFLD/NASH. Despite a vital physiological function of
      cholesterol, mitochondrial dysfunction is an important consequence of dietary
      induced hypercholesterolemia and was, subsequently, linked to many
      pathophysiological conditions. The aim in the current study was to evaluate the
      morphological and molecular changes of cholesterol overload in mouse liver and
      particularly, in mitochondria, induced by a high-cholesterol (HC) diet for one
      month. Histopathological studies revealed microvesicular hepatic steatosis and
      significantly elevated levels of liver cholesterol and triglycerides leading to
      impaired liver synthesis. Further, high levels of oxidative stress could be
      determined in liver tissue as well as primary hepatocyte culture. Transcriptomic
      changes induced by the HC diet involved disruption in key pathways related to
      cell death and oxidative stress as well as upregulation of genes related to
      glutathione homeostasis. Impaired liver function could be associated with a
      decrease in mitochondrial membrane potential and ATP content and significant
      alterations in mitochondrial dynamics. We demonstrate that cholesterol overload
      in the liver leads to mitochondrial changes which may render damaged hepatocytes
      proliferative and resistant to cell death whereby perpetuating liver damage.

PMID- 30239005
TI  - Curcumin: A naturally occurring autophagy modulator.
AB  - Autophagy is a self-degradative process that plays a pivotal role in several
      medical conditions associated with infection, cancer, neurodegeneration, aging,
      and metabolic disorders. Its interplay with cancer development and treatment
      resistance is complicated and paramount for drug design since an autophagic
      response can lead to tumor suppression by enhancing cellular integrity and
      tumorigenesis by improving tumor cell survival. In addition, autophagy denotes
      the cellular ability of adapting to stress though it may end up in apoptosis
      activation when cells are exposed to a very powerful stress. Induction of
      autophagy is a therapeutic option in cancer and many anticancer drugs have been
      developed to this aim. Curcumin as a hydrophobic polyphenol compound extracted
      from the known spice turmeric has different pharmacological effects in both in
      vitro and in vivo models. Many reports exist reporting that curcumin is capable
      of triggering autophagy in several cancer cells. In this review, we will focus on
      how curcumin can target autophagy in different cellular settings that may extend
      our understanding of new pharmacological agents to overcome relevant diseases.

PMID- 30239007
TI  - Misogynistic peers, masculinity, and bystander intervention for sexual
      aggression: Is it really just "locker-room talk?"
AB  - The present study utilized a laboratory paradigm to examine the extent to which
      bystander behavior for sexual aggression is independently and jointly influenced
      by situational misogynistic peer norms and men's adherence to hegemonic male
      norms. Participants were a racially diverse college sample of self-identified
      heterosexual men (N = 104) between the ages of 18-35. Men completed a measure of
      hegemonic masculinity and engaged in a laboratory paradigm in which they and
      three male confederates watched a female confederate, who reported a strong
      dislike of sexual content in the media, view a sexually explicit film which they
      could stop at any time. Prior to the woman viewing the film, participants were
      randomly assigned to a peer norm manipulation wherein the male confederates set a
      misogynistic or ambiguous norm. Results indicated the presence of a misogynistic
      peer norm decreased the likelihood and speed of intervention. Among men exposed
      to misogynistic, compared to ambiguous, peer norms, men who strongly endorsed the
      status male role norm were less likely to display prosocial bystander behavior.
      Findings indicate that exposure to peers who sexually objectify and disrespect
      women decreases prosocial bystander intervention. Further, these findings provide
      evidence that misogynistic peer norms heighten men's adherence to a hegemonic
      masculinity that men should attain social status, thereby deterring bystander
      behavior for sexual aggression.

PMID- 30239006
TI  - Schistosoma mansoni schistosomula antigens induce Th1/Pro-inflammatory cytokine
      responses.
AB  - Larvae of Schistosoma (schistosomula) are highly susceptible to host immune
      responses and are attractive prophylactic vaccine targets, although cellular
      immune responses against schistosomula antigens in endemic human populations are
      not well characterized. We collected blood and stool from 54 Schistosoma mansoni
      infected Ugandans, isolated peripheral blood mononuclear cells and stimulated
      them for 24 hours with schistosome adult worm and soluble egg antigens (AWA and
      SEA), along with schistosomula recombinant proteins rSmKK7, Lymphocyte Antigen 6
      isoforms (rSmLy6A and rSmLy6B), tetraspanin isoforms (rSmTSP6 and rSmTSP7).
      Cytokines, chemokines and growth factors were measured in the culture
      supernatants using a multiplex luminex assay, and infection intensity was
      determined before and at 1 year after praziquantel (PZQ) treatment using the Kato
      Katz method. Cellular responses were grouped and the relationship between groups
      of correlated cellular responses and infection intensity before and after PZQ
      treatment was investigated. AWA and SEA induced mainly Th2 responses. In
      contrast, rSmLy6B, rSmTSP6 and rSmTSP7 induced Th1/pro-inflammatory responses.
      While recombinant antigens rSmKK7 and rSmLy6A did not induce a Th1/pro
      inflammatory response, they had an association with pre-treatment infection
      intensity after adjusting for age and sex. Testing more schistosomula antigens
      using this approach could provide immune-epidemiology identifiers necessary for
      prioritizing next generation schistosomiasis vaccine candidates.

PMID- 30239008
TI  - Effects of sauna bath on heart failure: A systematic review and meta-analysis.
AB  - BACKGROUND: Sauna bath has potential as a lifestyle treatment modality for heart
      failure (HF). It is important to analyze the current evidence to help suggest
      paths of future study and potential for clinical application. HYPOTHESIS: Sauna
      bath has a positive effect on HF patients. METHODS: PubMed, Cochrane Library, and
      CINAHL databases were searched to identify randomized and nonrandomized
      controlled studies to compare effects of sauna bath with no sauna bath. Studies
      were searched for both infrared sauna bath and Finnish sauna bath. The strength
      of evidence was rated using a modified GRADE approach. Out of 1444 studies, nine
      met the inclusion criteria and were included in this review. Seven of these nine
      studies were included in the meta-analysis. Only studies with infrared sauna bath
      met the inclusion criteria. RESULTS: In the meta-analysis, exposure to an
      infrared sauna bath in 60 degrees C for 15 minutes, followed by a 30-minute rest
      in warm environment, five times a week for 2 to 4 weeks, was associated with a
      significant reduction in B-type natriuretic peptide, cardiothoracic ratio, and an
      improvement in left-ventricular ejection fraction. There was no significant
      effect on left-ventricular end-diastolic diameter, left atrial diameter, systolic
      blood pressure, or diastolic blood pressure. The strength of evidence varied from
      moderate to insufficient. CONCLUSION: Infrared sauna bath was associated with
      short-term improvement in cardiac function. More evidence is needed about long
      term effects of sauna bath and the effects of a Finnish sauna on cardiovascular
      health among patients with HF or other cardiovascular diseases.

PMID- 30239009
TI  - Prolonged electromechanical delay as an early predictor of trastuzumab-induced
      cardiotoxicity in patients undergoing treatment for breast cancer.
AB  - BACKGROUND: We aimed to investigate if left ventricular electromechanical delay
      (LVEMD) prolongation predicts trastuzumab-induced cardiotoxicity (TIC) in breast
      cancer patients. HYPOTHESIS: LVEMD prolongation on serial echocardiograms could
      be an indicator of subclinical TIC. METHODS: We included 237 breast cancer
      patients receiving trastuzumab chemotherapy, who underwent echocardiography at
      baseline and at 6 and 12 months after trastuzumab initiation. LVEMD was defined
      as the time from electrical activation to myocardial contraction. TIC was defined
      as left ventricular ejection fraction (LVEF) worsening to <55%, either as
      symptomatic decrease of >=5% or asymptomatic decrease of >=10%. RESULTS: During a
      mean follow-up of 547 days, TIC occurred in 27 patients (11.4%). Changes in the
      time intervals from QRS onset on electrocardiography to the beginning and peak of
      transaortic flow on pulsed-wave Doppler echocardiography (ie, DeltaLVEMDi and
      DeltaLVEMDp, respectively) were independent predictors of TIC. On receiver
      operating characteristic curve analysis, the optimal cutoff value for TIC
      prediction was 23 milliseconds for DeltaLVEMDi (sensitivity, 0.85; specificity,
      0.78; area under the curve [AUC], 0.882) and 21 milliseconds for DeltaLVEMDp
      (sensitivity, 0.96; specificity, 0.68; AUC, 0.860). The C-index for TIC
      prediction increased significantly after adding DeltaLVEMDi and DeltaLVEMDp to
      conventional models that included clinical variables, baseline LVEF, and changes
      in global longitudinal peak systolic strain. Similarly, adding DeltaLVEMDi or
      DeltaLVEMDp to conventional models provided significant improvement in
      discrimination capability for TIC prediction (integrated discrimination
      improvement and continuous net reclassification improvement index). CONCLUSION:
      DeltaLVEMDi and DeltaLVEMDp may serve as predictors of subclinical cardiac
      dysfunction in breast cancer patients receiving trastuzumab.

PMID- 30239010
TI  - Team-level identification predicts perceived and actual team performance:
      Longitudinal multilevel analyses with sports teams.
AB  - Social identification and team performance literatures typically focus on the
      relationship between individual differences in identification and individual
      level performance. By using a longitudinal multilevel approach, involving 369
      members of 45 sports teams across England and Italy, we compared how team-level
      and individual-level variance in social identification together predicted team
      and individual performance outcomes. As hypothesized, team-level variance in
      identification significantly predicted subsequent levels of both perceived and
      actual team performance in cross-lagged analyses. Conversely, individual-level
      variance in identification did not significantly predict subsequent levels of
      perceived individual performance. These findings support recent calls for social
      identity to be considered a multilevel construct and highlight the influence of
      group-level social identification on group-level processes and outcomes, over and
      above its individual-level effects.

PMID- 30239011
TI  - The determination of the infectious status and prevalence of motile Aeromonas
      species isolated from disease cases in rainbow trout (Oncorhynchus mykiss) and
      aquarium fish.
AB  - The aims of this study were to determine the prevalence and phylogenetic
      relationship of motile Aeromonas spp. that might be pathogenic species for
      rainbow trout in infected/mix infection cases (based upon different outbreaks on
      fish farms). A total of 99 motile Aeromonas isolates (and three reference
      strains) were analysed that were isolated from four different fish species in
      different sizes of fish (0.1-3,000 g), different months and water temperatures
      (6.1-21.2 degrees C). The biochemical characteristics of the isolates were
      determined using conventional tests and a rapid test kit. Additionally, molecular
      identification was performed using the gyrB housekeeping gene region and with
      glycerophospholipid-cholesterol acyltransferase polymerase chain reaction (GCAT
      PCR). The sequencing results obtained from the gyrB gene region were deposited in
      the GenBank database, and phylogenetic relationships were determined with the
      BioNumerics 7.6 database. Nearly half of the Aeromonas isolates that were
      isolated from rainbow trout showing signs of disease were determined to be
      possible infectious agents. Aeromonas species exhibit biochemical variability for
      many characters, so some Aeromonas species tested negative for GCAT-PCR despite
      that this test was created especially for Aeromonas identification. The
      phylogenetic tree based upon gyrB contained 10 different phylogroups that were
      based on 96% cut-off value in gyrB gene region.

PMID- 30239012
TI  - Antibody responses to Schistosoma mansoni schistosomula antigens.
AB  - While antigens from Schistosoma schistosomula have been suggested as potential
      vaccine candidates, the association between antibody responses with schistosomula
      antigens and infection intensity at reinfection is not well known. Schistosoma
      mansoni-infected individuals were recruited from a schistosomiasis endemic area
      in Uganda (n = 372), treated with 40 mg/kg praziquantel (PZQ) and followed up at
      five weeks and at one year post-treatment. Pre-treatment and five weeks post
      treatment immunoglobulin (Ig) E, IgG1 and IgG4 levels against recombinant
      schistosomula antigens rSmKK7, rSmLy6A, rSmLy6B and rSmTSP7 were measured using
      ELISA. Factors associated with detectable pre-treatment or post-treatment
      antibody response against the schistosomula antigens and the association between
      five-week antibody responses and one year post-treatment reinfection intensity
      among antibody responders were examined. Being male was associated with higher
      pre-treatment IgG1 to rSmKK7, rSmLy6a and AWA. Five weeks post-treatment antibody
      responses against schistosomula antigens were not associated with one year post
      treatment reinfection intensity among antibody responders' antibody levels
      against rSmKK7, rSmLy6B and rSmTSP7 dropped, but increased against rSmLy6A, AWA
      and SEA at five weeks post-treatment among antibody responders. S. mansoni
      infected individuals exhibit detectable antibody responses to schistosomula
      antigens that are affected by treatment. These findings indicate that
      schistosomula antigens induce highly varied antibody responses and could have
      implications for vaccine development.

PMID- 30239014
TI  - Prematurity and cardiovascular risk at early adulthood.
AB  - BACKGROUND: Theories of early stress exposure and allostatic load offer a
      lifespan perspective to adult health after prematurity based on these early
      stressors affecting endocrine and metabolic systems. In this study, we examine
      cardiovascular and metabolic risk by comparing two groups of preterm infants who
      experienced a full spectrum of neonatal illness and a term-born group at age 23.
      METHODS: Of the 215 infants recruited at birth, 84% participated at age 23. The
      cohort included 45 full-term (FT), 24 healthy preterm (HPT), and 111 sick preterm
      (SPT) infants. Socio-economic status was equivalent across groups. Cardiovascular
      and metabolic outcomes were as follows: blood pressure (BP), fasting glucose and
      lipid profiles, weight, waist-hip ratio (WHR), and body mass index (BMI).
      Clinical and subclinical ranges were compared across neonatal groups and gender.
      RESULTS: At age 23, the HPT and SPT groups had higher systolic BP compared with
      the FT group. The SPT group had lower weight compared with the FT and HPT groups.
      No group differences were found on diastolic BP, glucose, total cholesterol, high
      density lipids, low-density lipids, triglycerides, BMI, or WHR. Preterm males had
      more systolic hypertension and low high-density lipids than FT males. Former
      preterm males and females had high WHR ratios and BMI at 23 years. Subclinical
      prehypertensive rates were highest for the HPT female group, followed by the SPT
      females. Only one (4.2%) HPT adult male was clinically diabetic. CONCLUSIONS: As
      young adults, HPT and SPT infants had early indicators of cardiovascular risk but
      no indicators of metabolic risk. There is utility in using clinical and
      subclinical ranges to identify early cardiovascular risk in early adulthood.

PMID- 30239013
TI  - Biocompatibility of Polysulfone Hemodialysis Membranes and Its Mechanisms:
      Involvement of Fibrinogen and Its Integrin Receptors in Activation of Platelets
      and Neutrophils.
AB  - Activation of blood cells during hemodialysis is considered to be a significant
      determinant of biocompatibility of the hemodialysis membrane because it may
      affect patient health adversely through microvascular inflammation and oxidative
      stress. This study found very different cell activation among various polysulfone
      (PSf) hemodialysis membranes. For example, CX-U, a conventional PSf membrane,
      induced marked adhesion of platelets to its surface and increased surface
      expression of activated CD11b and production of reactive oxygen species (ROS) by
      neutrophils; while NV-U, a hydrophilic polymer-immobilized PSf membrane, caused
      little platelet adhesion and slight CD11b expression and ROS production by
      neutrophils. Analysis of the molecular mechanisms of the above phenomena on CX-U
      and NV-U indicated that anti-integrin GPIIb/IIIa antibody blocked platelet
      adhesion, and that the combination of anti-CD11b (integrin alpha subunit of Mac
      1) and anti-integrin alphavbeta3 antibodies blocked ROS production by
      neutrophils. Plasma-derived fibrinogen, a major ligand of GPIIb/IIIa, Mac-1, and
      alphavbeta3 on membranes, was thus analyzed and found to be more adsorbed to CX-U
      than to NV-U. Moreover, comparison between five PSf membranes showed that the
      number of adherent platelets and neutrophil ROS production increased with
      increasing fibrinogen adsorption. These results suggested that fibrinogen,
      adsorbed on membranes, induced GPIIb/IIIa-mediated platelet activation and Mac
      1/alphavbeta3-mediated neutrophil activation, depending on the amount of
      adsorption. In conclusion, the use of biocompatible membranes like NV-U, which
      show lower adsorption of fibrinogen, is expected to reduce hemodialysis-induced
      inflammation and oxidative stress by minimizing cell activation.

PMID- 30239015
TI  - sCARy! Risk Perceptions in Autonomous Driving: The Influence of Experience on
      Perceived Benefits and Barriers.
AB  - The increasing development of autonomous vehicles (AVs) influences the future of
      transportation. Beyond the potential benefits in terms of safety, efficiency, and
      comfort, also potential risks of novel driving technologies need to be addressed.
      In this article, we explore risk perceptions toward connected and autonomous
      driving in comparison to conventional driving. In order to gain a deeper
      understanding of individual risk perceptions, we adopted a two-step empirical
      procedure. First, focus groups ( N=17 ) were carried out to identify relevant
      risk factors for autonomous and connected driving. Further, a questionnaire was
      developed, which was answered by 516 German participants. In the questionnaire,
      three driving technologies (connected, autonomous, conventional) were evaluated
      via semantic differential (rating scale to identify connotative meaning of
      technologies). Second, participants rated perceived risk levels (for data,
      traffic environment, vehicle, and passenger) and perceived benefits and barriers
      of connected/autonomous driving. Since previous experience with automated
      functions of driver assistance systems can have an impact on the evaluation,
      three experience groups have been formed. The effect of experience on benefits
      and barrier perceptions was also analyzed. Risk perceptions were significantly
      smaller for conventional driving compared to connected/autonomous driving. With
      increasing experience, risk perception decreases for novel driving technologies
      with one exception: the perceived risk in handling data is not influenced by
      experience. The findings contribute to an understanding of risk perception in
      autonomous driving, which helps to foster a successful implementation of AVs on
      the market and to develop public information strategies.

PMID- 30239016
TI  - Global folate status in women of reproductive age: a systematic review with
      emphasis on methodological issues.
AB  - Inadequate folate status in women of reproductive age (WRA) can lead to adverse
      health consequences of public health significance, such as megaloblastic anemia
      (folate deficiency) and an increased risk of neural tube defect (NTD)-affected
      pregnancies (folate insufficiency). Our review aims to evaluate current data on
      folate status of WRA. We queried eight databases and the World Health
      Organization Micronutrients Database, identifying 45 relevant surveys conducted
      between 2000 and 2014 in 39 countries. Several types of folate assays were used
      in the analysis of blood folate, and many surveys used folate cutoffs not matched
      to the assay. To allow better comparisons across surveys, we attempted to account
      for these differences. The prevalence of folate deficiency was >20% in many
      countries with lower income economies but was typically <5% in countries with
      higher income economies. Only 11 surveys reported the prevalence of folate
      insufficiency, which was >40% in most countries. Overall, folate status data for
      WRA globally are limited and must be carefully interpreted due to methodological
      issues. Future surveys would benefit from using the microbiologic assay to assess
      folate status, along with assay-matched cutoffs to improve monitoring and
      evaluation of folic acid interventions, thus informing global efforts to prevent
      NTDs.

PMID- 30239017
TI  - Stratifying Minimal Versus Severe Pain in Knee Osteoarthritis Using a
      Musculoskeletal Ultrasound Protocol.
AB  - OBJECTIVE: The aim of this cross-sectional correlational study was to determine
      the association of pain with morphologic and inflammatory sonographic findings in
      patients with knee osteoarthritis. METHODS: A total of 113 participants with knee
      osteoarthritis were assessed using visual analog scale pain score and sonography.
      Ultrasound evaluation included morphologic changes (ie, articular cartilage
      degeneration, medial and lateral meniscal protrusion, and presence of osteophytes
      on the joint margins) and inflammatory changes (ie suprapatellar effusion and/or
      synovitis, Baker cyst, superficial and deep infrapatellar effusion, pes anserine
      tendinopathy, and Hoffa panniculitis). RESULTS: Cluster analysis via Ward's
      method grouped patients with minimal pain (visual analog scale score, 0-4) and
      with substantial pain (visual analog scale score, 5-10). Stepwise logistic
      regression yielded 5 variables that significantly explained the variation in the
      probability of perceived substantial pain at 10% level of significance: lateral
      cartilage clarity (LCC; P = .025), medial cartilage clarity (MCC; P = .20),
      medial cartilage thickness (MCT; P = .041), medial meniscus protrusion (MMP) (P =
      .029), and osteophytes at medial femoral margin (P = .082), with 63% overall
      prediction accuracy. When age and sex were added, 4 variables remained
      significant at a 10% level of significance: LCC, MCC, MCT, and MMP, with 65%
      overall prediction accuracy. The receiver operating characteristic curve of this
      model was 0.667. CONCLUSION: The study was able to demonstrate that morphologic
      abnormalities in the ultrasound parameters for LCC, MCC, MCT, and MMP were able
      to predict significant joint pain in knee osteoarthritis. There were no
      inflammatory changes that contributed to significant joint pain in this study.

PMID- 30239018
TI  - When Is a Risk Assessment Deficient According to an Uncertainty-Based Risk
      Perspective?
AB  - The Petroleum Safety Authority Norway (PSA-N) has recently adopted a new
      definition of risk: "the consequences of an activity with the associated
      uncertainty." The PSA-N has also been using "deficient risk assessment" for some
      time as a basis for assigning nonconformities in audit reports. This creates an
      opportunity to study the link between risk perspective and risk assessment
      quality in a regulatory context, and, in the present article, we take a hard look
      at the term "deficient risk assessment" both normatively and empirically. First,
      we perform a conceptual analysis of how a risk assessment can be deficient in
      light of a particular risk perspective consistent with the new PSA-N risk
      definition. Then, we examine the usages of the term "deficient" in relation to
      risk assessments in PSA-N audit reports and classify these into a set of
      categories obtained from the conceptual analysis. At an overall level, we were
      able to identify on what aspects of the risk assessment the PSA-N is focusing and
      where deficiencies are being identified in regulatory practice. A key observation
      is that there is a diversity in how the agency officials approach the risk
      assessments in audits. Hence, we argue that improving the conceptual clarity of
      what the authorities characterize as "deficient" in relation to the uncertainty
      based risk perspective may contribute to the development of supervisory practices
      and, eventually, potentially strengthen the learning outcome of the audit
      reports.

PMID- 30239019
TI  - Advances in cellular and integrative control of oxygen and carbon dioxide
      homeostasis.

PMID- 30239020
TI  - Stepwise basis set selection.
AB  - The computational cost of quantum chemical methods grows rapidly with increasing
      level of theory and basis set size. At increasing costs, higher accuracies can be
      reached, forcing a compromise between cost and accuracy for most molecular
      systems. Heats of reaction, however, are mostly determined by a subset of atoms
      that experience significant bonding and/or electronic changes. To exploit this
      fact, the Stepwise Basis Builder (SBB) algorithm selectively adds basis functions
      to reactive atoms and maintains small basis sets on spectator atoms. This article
      introduces the SBB algorithm and how it chooses a basis for each atom, predicts
      calculation errors, and uses these predicted errors to reach target levels of
      accuracy. Benchmarks show SBB heats of reaction and activation barriers converge
      to values consistent with higher-quality calculations using a greatly reduced
      number of basis functions. (c) 2018 Wiley Periodicals, Inc.

PMID- 30239021
TI  - Lost in Translation? Integrating Interdisciplinary Disaster Research with Policy
      Praxis.
AB  - Interdisciplinary research can help address complex issues such as community
      resilience and climate change. However, transcending disciplinary borders to
      provide better understandings of these cross-cutting issues is not an easy task.
      While there has been a greater focus on improving integration across disciplines,
      less attention has been paid to the particular challenges in the inclusion and
      integration of policy praxis into interdisciplinary research. This article argues
      that to effectively integrate policy-relevant goals, researchers need to
      understand the obstacles to transcending disciplinary borders to incorporate the
      perspectives of policy practitioners. Researchers also need to understand
      problems in integration when it takes place within research groups or entities
      comprised of a variety of scholars from diverse disciplines working with a set of
      practitioners from different agencies or levels of government. Impediments to
      integration include epistemological, disciplinary, and attitudinal barriers,
      differences in terminologies and timescales, the role of organizational culture,
      institutional barriers, data issues, and issues related to risk communication and
      liability. This article explores these challenges and how they affect the
      translation of interdisciplinary and transdisciplinary research. It concludes
      with recommendations to help overcome challenges in synthesizing disaster
      research and policy practices and to enrich interdisciplinary disaster research
      approaches and designs.

PMID- 30239022
TI  - Development of analytical method for the quality control of the fruit bark of
      Punica granatum L. (pomegranate) and antichemotatic activity of extract and rich
      fraction in punicalagins.
AB  - Pomegranate is of current interest owing to the existing potential for industrial
      uses of fruit peels. This includes its availability as a raw vegetable material,
      a byproduct that constitutes residue in the use of the species and is recognized
      as a functional product, and beneficial health properties, as will be
      demonstrated in the studies cited. Therefore, it is necessary to ensure its
      effectiveness and safety. Toward this end, the aim of this study was to develop
      and validate an analytical method for the separation and quantification of total
      punicalagin present in the bark of the fruit of Punica granatum by HPLC. Purity
      tests such as water determination and total ashes were also performed. The
      ability of the extract and enriched fraction of punicalagin to inhibit leukocyte
      migration in vitro was determined by the Boyden's chamber method. The developed
      HPLC method demonstrated good separation and quantification of the punicalagin
      alpha and beta anomers. The method is efficient and reliable, and can ultimately
      be used for the analysis of the extract of pomegranate. The crude extract and the
      fraction of punicalagins significantly inhibited leukocyte migration at
      concentrations of 1 and 10 MUg/mL in relation to the negative control, indicating
      potential antichemotactic action.

PMID- 30239023
TI  - Environmental Surveillance System Characteristics and Impacts on Confidence About
      No Undetected Serotype 1 Wild Poliovirus Circulation.
AB  - Surveillance for poliovirus during the polio endgame remains uncertain. Building
      on prior modeling of the potential for undetected poliovirus transmission for
      conditions like those in Pakistan and Afghanistan, we use a hypothetical model to
      explore several key characteristics of the poliovirus environmental surveillance
      (ES) system (e.g., number and quality of sites, catchment sizes, and sampling
      frequency) and characterize their impacts on the time required to reach high
      (i.e., 95%) confidence about no circulation (CNC95%) following the last detected
      case of serotype 1 wild poliovirus. The nature and quality of the existing and
      future acute flaccid paralysis (AFP) surveillance and ES system significantly
      impact the estimated CNC95% for places like Pakistan and Afghanistan. The
      analysis illustrates the tradeoffs between number of sites, sampling frequency,
      and catchments sizes, and suggests diminishing returns of increasing these three
      factors beyond a point that depends on site quality and the location of sites.
      Limitations in data quality and the hypothetical nature of the model reduce the
      ability to assess the extent to which actual ES systems offer benefits that
      exceed their costs. Thus, although poliovirus ES may help to reduce the time
      required to reach high confidence about the absence of undetected circulation,
      the effect strongly depends on the ability to establish effective ES sites in
      high-risk areas. The costs and benefits of ES require further analysis.

PMID- 30239024
TI  - Workforce/Population, Economy, Infrastructure, Geography, Hierarchy, and Time
      (WEIGHT): Reflections on the Plural Dimensions of Disaster Resilience.
AB  - The concept of resilience and its relevance to disaster risk management has
      increasingly gained attention in recent years. It is common for risk and
      resilience studies to model system recovery by analyzing a single or aggregated
      measure of performance, such as economic output or system functionality. However,
      the history of past disasters and recent risk literature suggest that a single
      dimension view of relevant systems is not only insufficient, but can compromise
      the ability to manage risk for these systems. In this article, we explore how
      multiple dimensions influence the ability for complex systems to function and
      effectively recover after a disaster. In particular, we compile evidence from the
      many competing resilience perspectives to identify the most critical resilience
      dimensions across several academic disciplines, applications, and disaster
      events. The findings demonstrate the need for a conceptual framework that
      decomposes resilience into six primary dimensions: workforce/population, economy,
      infrastructure, geography, hierarchy, and time (WEIGHT). These dimensions are not
      typically addressed holistically in the literature; often they are either modeled
      independently or in piecemeal combinations. The current research is the first to
      provide a comprehensive discussion of each resilience dimension and discuss how
      these dimensions can be integrated into a cohesive framework, suggesting that no
      single dimension is sufficient for a holistic analysis of a disaster risk
      management. Through this article, we also aim to spark discussions among
      researchers and policymakers to develop a multicriteria decision framework for
      evaluating the efficacy of resilience strategies. Furthermore, the WEIGHT
      dimensions may also be used to motivate the generation of new approaches for data
      analytics of resilience-related knowledge bases.

PMID- 30239025
TI  - UPLC-MS/MS method validation of ciprofloxacin in human urine: Application to
      biodegradability study in microbial fuel cell.
AB  - To enable the reliable quantification of ciprofloxacin in human urine, a
      sensitive and selective assay based on liquid chromatography-tandem mass
      spectrometry was developed. The chromatographic separation of the ciprofloxacin
      was carried out on a Zorbex Eclipse C18 column using methanol and ammonium
      acetate as a mobile phase by the gradient elution method. The developed assay
      covered a wide range of concentrations (1.56-100 ng/mL) with a lower limit of
      detection of 0.76 ng/mL. Quantification was performed using the multiple reaction
      monitoring transitions 331.8/231 for ciprofloxacin and 362/318 for ofloxacin
      (internal standard). This assay was validated for linearity, accuracy, precision
      and recovery. The validated method was then applied to the biodegradability of
      ciprofloxacin (99%) from human urine in the microbial fuel cell.

PMID- 30239026
TI  - Evaluation of Proactive and Reactive Strategies for Polio Eradication Activities
      in Pakistan and Afghanistan.
AB  - Only Pakistan and Afghanistan reported any polio cases caused by serotype 1 wild
      polioviruses (WPV1s) in 2017. With the dwindling cases in both countries and
      pressure to finish eradication with the least possible resources, a danger exists
      of inappropriate prioritization of efforts between the two countries and
      insufficient investment in the two countries to finish the job. We used an
      existing differential-equation-based poliovirus transmission and oral poliovirus
      (OPV) evolution model to simulate a proactive strategy to stop transmission, and
      different hypothetical reactive strategies that adapt the quality of supplemental
      immunization activities (SIAs) in response to observed polio cases in Pakistan
      and Afghanistan. To account for the delay in perception and adaptation, we
      related the coverage of the SIAs in high-risk, undervaccinated subpopulations to
      the perceived (i.e., smoothed) polio incidence. Continuation of the current
      frequency and quality of SIAs remains insufficient to eradicate WPV1 in Pakistan
      and Afghanistan. Proactive strategies that significantly improve and sustain SIA
      quality lead to WPV1 eradication and the prevention of circulating vaccine
      derived poliovirus (cVDPV) outbreaks. Reactive vaccination efforts that adapt
      moderately quickly and independently to changes in polio incidence in each
      country may succeed in WPV1 interruption after several cycles of outbreaks, or
      may interrupt WPV1 transmission in one country but subsequently import WPV1 from
      the other country or enable the emergence of cVDPV outbreaks. Reactive
      vaccination efforts that adapt independently and either more rapidly or more
      slowly to changes in polio incidence in each country may similarly fail to
      interrupt WPV1 transmission and result in oscillations of the incidence. Reactive
      strategies that divert resources to the country of highest priority may lead to
      alternating large outbreaks. Achieving WPV1 eradication and subsequent successful
      OPV cessation in Pakistan and Afghanistan requires proactive and sustained
      efforts to improve vaccination intensity in under-vaccinated subpopulations while
      maintaining high population immunity elsewhere.

PMID- 30239027
TI  - Fibular osteotomy to facilitate proximal tibial rotation during tibial plateau
      leveling osteotomy.
AB  - OBJECTIVE: To identify factors that restrict proximal tibial rotation during
      tibial plateau leveling osteotomy (TPLO) and report on the outcome of concurrent
      fibular osteotomy (TPLO-FO). STUDY DESIGN: Retrospective case-control study.
      ANIMALS: Dogs undergoing TPLO-FO (n = 23) and dogs undergoing routine TPLO (n =
      49). METHODS: Medical records and radiographs of dogs that had undergone TPLO-FO
      were reviewed. Data that were collected included signalment, preoperative tibial
      plateau angle (TPA), mechanical medial proximal tibial angle (mMPTA),
      postoperative and recheck TPA and mMPTA, ratio of fibular width to tibial width
      (FW:TW), presence of tibiofibular synostosis, tibial osteotomy location, and use
      of additional implants. RESULTS: The odds of exhibiting rotational constraints
      requiring FO during TPLO were 62-fold greater in dogs with tibiofibular
      synostosis than in dogs without synostosis. Dogs with FW:TW greater than 0.24
      were 7.8-fold more likely to exhibit rotational constraints. After TPLO-FO, the
      postoperative increase in TPA was greater after single-plate fixation (mean, 5.4 
      degrees  +/- 4.5  degrees ) compared with fixation with 2 plates (mean, 1.4 
      degrees  +/- 0.6  degrees ). CONCLUSION: Proximal tibiofibular synostosis and a
      relatively wide fibula restricted tibial plateau rotation. In these dogs,
      concurrent fibular osteotomy allowed adequate rotation. Adjunct plate fixation
      limited loss of rotation after TPLO-FO. CLINICAL SIGNIFICANCE: Successful TPLO
      relies on adequate rotation of the proximal tibial segment. Fibular osteotomy and
      adjunct plate fixation are recommended to achieve and maintain adequate rotation
      of the osteotomized tibia in dogs with rotational constraints.

PMID- 30239028
TI  - Vitamin D deficiency and electrocardiographic subclinical myocardial injury:
      Results from National Health and Nutrition Examination Survey-III.
AB  - BACKGROUND: Association of cardiovascular disease (CVD) with nontraditional risk
      factors such as vitamin D deficiency has been examined previously. An
      investigation of the association of vitamin D with subclinical myocardial injury
      (SC-MI) based on an electrocardiographic score is a simple, cost-effective and
      innovative way to explore this relationship. HYPOTHESIS: We hypothesize that low
      vitamin D levels will be associated with prevalent SC-MI independent of
      traditional CVD risk factors, lifestyle factors, and socioeconomic status.
      METHODS: This analysis included 6079 participants (58.3 +/- 13.1 years; 54.1%
      women) without CVD from the third National Health and Nutrition Examination
      Survey. A multivariable logistic regression model was used to examine the
      association between vitamin D categories (<20, 20-29, and >30 ng/mL (reference)
      and cardiac injury score. RESULTS: There was an incremental increase in the
      prevalence of SC-MI across vitamin D categories with the highest prevalence in
      <20 ng/mL, followed by 20 to 29 ng/mL and then >30 ng/mL (trend P-value <0.0001).
      There was a statistically significant association between vitamin D deficiency
      (<20 ng/mL) and SC-MI (odds ratio [OR] (95% confidence interval [CI]): 1.27 (1.04
      1.55), P = 0.04). This association was stronger in men than women (OR (95% CI):
      1.74 (1.32-2.30) vs 0.94 (0.70-1.25) respectively; interaction P-value 0.002).
      CONCLUSIONS: Vitamin D deficiency is associated with SC-MI, especially in men.
      These findings may further highlight the role of nontraditional risk factors in
      the development of CVD. The value of vitamin D supplementation in the prevention
      of myocardial ischemia and injury may warrant investigation.

PMID- 30239029
TI  - Prevalence of potential contact allergens in baby cosmetic products.
AB  - Allergic contact dermatitis (ACD) is an increasing problem in children. We sought
      to investigate the extent of haptens or contact allergens present in baby
      cosmetic products. Computer programming scripts were written to web-scrape UK
      supermarkets and pharmacies. In total, 438 unique 'baby products' were
      identified, and constituent ingredient information was extracted. Data were cross
      referenced against 10 standardized patch test reference series. We found that 88%
      of products had at least one reference contact allergen. There was a mean of 2.21
      (range 1-15) reference allergens per product. The most abundant compounds were
      parabens, fragrances, cetyl/steryl alcohol, methylisothiazolinone, sodium lauryl
      sulfate and lanolin alcohol. Branded products and those marketed as
      'sensitive/gentle/organic/fragrance-free' appeared to contain a greater number of
      reference allergens than those not marketed as such. This study highlights the
      increasing number of cosmetic products targeted to children in the UK, and the
      extent of potential allergens present in these products.

PMID- 30239030
TI  - Neurofilament is superior to cytokeratin 20 in supporting cutaneous origin for
      neuroendocrine carcinoma.
AB  - AIM: Primary cutaneous neuroendocrine carcinoma, or Merkel cell carcinoma (MCC),
      cannot be distinguished morphologically from small-cell neuroendocrine carcinomas
      (SmCC) from other sites. Immunohistochemistry is required to confirm cutaneous
      origin, and is also used for detection of sentinel lymph node (SLN) metastases of
      MCC. Cytokeratin 20 (CK20) expression is commonly used for these purposes, but is
      negative in some MCC cases, and has unclear specificity. We evaluated
      immunohistochemistry for neurofilament and CK20 in MCC compared with SmCC from
      other sites. METHODS AND RESULTS: We evaluated neurofilament expression in 55 MCC
      specimens from 39 unique patients, including nine CK20-negative MCC tumours.
      Neurofilament expression was observed in 42 of 55 (76.4%) MCC cases, including
      seven of nine (77.8%) CK20-negative MCC cases. Neurofilament was expressed in
      nine of 12 (75%) Merkel cell polyomavirus-positive tumours and five of 10 (50%)
      virus-negative tumours. Compared to a standard immunohistochemical panel
      (cytokeratin cocktail and CK20), neurofilament was 87.5% sensitive for detecting
      SLN metastases. Neurofilament and CK20 expression was also assessed in 61
      extracutaneous SmCC from 60 unique patients, with primary sites including lung
      (27), bladder (18), cervix (3), gastrointestinal tract (3), sinonasal tract (2)
      and other sites (7). The specificity of neurofilament and CK20 for MCC versus non
      cutaneous SmCC was 96.7% and 59.0%, respectively. CONCLUSIONS: Neurofilament has
      superior specificity to CK20 in distinguishing MCC from non-cutaneous SmCC.
      Neurofilament is frequently expressed in CK20- and virus-negative MCC tumours.
      Limitations of neurofilament immunohistochemistry include lower sensitivity than
      CK20 and subtle staining in some tumours. However, our findings indicate that
      neurofilament is useful for excluding non-cutaneous SmCC.

PMID- 30239032
TI  - Liver stiffness assessed by transient elastography as a potential indicator of
      chronic kidney disease in patients with nonalcoholic fatty liver disease.
AB  - BACKGROUND: This study was designed to determine the diagnostic value of liver
      stiffness measured by transient elastography (TE) in identifying chronic kidney
      disease (CKD) in individuals with ultrasonography-diagnosed NAFLD. METHODS: A
      total of 1439 adult patients with ultrasonography-diagnosed NAFLD between October
      2015 and August 2017 in China-Japan union hospital of Jilin university were
      initially eligible. According to the exclusion criteria, 24 patients were
      excluded, and eventually, a total of 1415 patients were included in the study.
      The AST/ALT ratio and FIB-4 score were calculated from blood tests, and liver
      stiffness was measured using TE. RESULTS: The liver stiffness measured by TE, FIB
      4 score, ALT/AST ratio were significantly elevated in CKD patients, compared with
      those without CKD (P < 0.001). The areas under the curve (AUROC) of liver
      stiffness, FIB-4 score and AST/ALT ratio were 0.694 (0.670-0.718), 0.707 (0.682
      0.730), 0.712 (0.688-0.736), showing no statistically significant difference
      between these three tests. Further, multivariate analysis identified four
      independent risk factors for CKD: age, diabetes mellitus, serum uric acid, and
      liver stiffness. Also, the performance of these four independent variables taken
      together in a logistic regression model for identifying CKD was 0.834 (AUROC;
      95%CI: 0.814-0.853), showing a higher diagnostic performance than that of a
      single application of liver stiffness. CONCLUSIONS: Liver stiffness assessed by
      TE is a potential indicator for CKD in ultrasonography-diagnosed NAFLD patients.
      Further, a four-variable model (liver stiffness, age, serum uric acid, and
      diabetes mellitus) could be a useful tool for identifying subjects at high risk
      for CKD in NAFLD patients.

PMID- 30239031
TI  - Association of serum adropin with the presence of atrial fibrillation and atrial
      remodeling.
AB  - OBJECTIVE: Adropin, a newly identified regulatory protein encoded by Enho gene,
      suppressed tumor necrosis factor alpha-induced THP1 monocyte adhesion to human
      umbilical vein endothelial cells. In addition, inflammation is demonstrated to be
      involved in the mechanism of atrial fibrillation (AF). Atrial remodeling is
      correlated with the persistence and progression of AF. Adropin is hypothesized to
      correlated with AF and atrial remodeling. This study aims to determine the
      correlation of serum adropin and the presence of AF and remodeling. METHODS: This
      study consisted of 344 AF patients and 210 healthy controls. AF patients were
      then divided into three subgroups of paroxysmal AF, persistent AF, and permanent
      AF. Serum adropin concentrations were examined using enzyme-linked immunosorbent
      assay method. Left atrial diameter (LAD) was measured to evaluate atrial
      remodeling. RESULTS: Decreased serum adropin concentrations were found in AF
      patients compared with healthy controls. Logistic regression analysis confirmed
      that serum adropin was inversely associated with the presence of AF (OR 0.218,
      95% CI 0.15-0.316; P < 0.001). Permanent AF patients had significantly reduced
      serum adropin concentrations compared with persistent and paroxysmal AF patients.
      There were decreased serum adropin concentrations in persistent AF group than
      those in paroxysmal AF group. Simple linear regression analyses showed that serum
      adropin in AF patients were negatively correlated with BMI, SBP, and LAD.
      Multiple stepwise regression analysis showed that LAD remained to be inversely
      associated with serum adropin (beta = 0.2, P = 0.010). CONCLUSION: Serum adropin
      concentrations are inversely correlated with the presence of AF and atrial
      remodeling.

PMID- 30239033
TI  - Subradiological silicosis.
AB  - The purpose of this commentary is to bring the neglected phenomenon of
      subradiological silicosis and its implications to the attention of readers. We
      define subradiological silicosis as silicosis detectable on pathological
      examination of lung tissue but not visible radiologically. For extent of the
      phenomenon, we draw on a study using a large South African autopsy database of
      deceased miners and chest radiographs taken in life. At an International Labour
      Organization threshold of >1/0 only 43% of all pathologically detected cases were
      detected on chest radiograph, and only 62% of those classified on pathology as
      "moderate or marked" silicosis. Subradiological silicosis has a number of
      implications for research and practice: for dose-response studies of silicosis;
      for studies of the relationship between silica and conditions such as
      tuberculosis, lung cancer, and autoimmune disease, including the mechanistic role
      of fibrogenesis; for prognostication in silica exposed workers; and for workers'
      compensation criteria.

PMID- 30239034
TI  - Repair of an adult aorto-pulmonary artery fistula associated with a ruptured
      aortic arch aneurysm using a frozen elephant trunk technique.
AB  - We describe the repair of an acute aorto-pulmonary artery fistula in a 82-year
      old patient with a ruptured aortic arch aneurysm using a frozen elephant trunk
      technique.

PMID- 30239035
TI  - Recognizability of heterologous co-chaperones with Streptococcus intermedius DnaK
      and Escherichia coli DnaK.
AB  - Streptococcus intermedius DnaK complements the temperature-sensitive phenotype of
      an Escherichia coli dnaK null mutant only when co-chaperones DnaJ and GrpE are co
      expressed. Therefore, whether S. intermedius DnaK and E. coli DnaK can recognize
      heterologous co-chaperones in vitro was examined. Addition of heterologous GrpE
      to DnaK and DnaJ partially stimulated adenosine triphosphatase (ATPase) activity,
      and almost completely stimulated luciferase refolding activity. Addition of
      heterologous DnaJ to GrpE and DnaK also stimulated ATPase activity; however,
      significant luciferase refolding activity was not observed. Moreover, E. coli
      DnaJ had a negative effect on the luciferase refolding activity of the S.
      intermedius DnaK chaperone system. In E. coli chaperone mutants, with the
      exception of E. coli DnaJ, stronger expression of the heterologous co-chaperones
      partially or almost completely complemented the temperature-sensitive-phenotype.
      These results indicate that all heterologous co-chaperones can at least partially
      recognize DnaK of a distantly related species. A region of the ATPase domain that
      is present in the DnaK of gram-negative bacteria is absent from the DnaK of gram
      positive bacteria. This region is believed to be important for recognition of co
      chaperones from gram-negative bacteria. However, insertion of this segment into
      S. intermedius DnaK failed to increase its ability to recognize E. coli co
      chaperones, implying that this region is unnecessary or insufficient for the
      recognition of E. coli co-chaperones. Thus, our data suggest that a basic
      structural similarity is conserved among the components of the S. intermedius and
      E. coli DnaK chaperone systems, allowing weak associations between heterologous
      components.

PMID- 30239036
TI  - Separating fetal and maternal placenta circulations using multiparametric MRI.
AB  - PURPOSE: The placenta is a vital organ for the exchange of oxygen, nutrients, and
      waste products between fetus and mother. The placenta may suffer from several
      pathologies, which affect this fetal-maternal exchange, thus the flow properties
      of the placenta are of interest in determining the course of pregnancy. In this
      work, we propose a new multiparametric model for placental tissue signal in MRI.
      METHODS: We describe a method that separates fetal and maternal flow
      characteristics of the placenta using a 3-compartment model comprising fast and
      slowly circulating fluid pools, and a tissue pool is fitted to overlapping
      multiecho T2 relaxometry and diffusion MRI with low b-values. We implemented the
      combined model and acquisition on a standard 1.5 Tesla clinical system with
      acquisition taking less than 20 minutes. RESULTS: We apply this combined
      acquisition in 6 control singleton placentas. Mean myometrial T2 relaxation time
      was 123.63 (+/-6.71) ms. Mean T2 relaxation time of maternal blood was 202.17 (+/
      92.98) ms. In the placenta, mean T2 relaxation time of the fetal blood component
      was 144.89 (+/-54.42) ms. Mean ratio of maternal to fetal blood volume was 1.16
      (+/-0.6), and mean fetal blood saturation was 72.93 (+/-20.11)% across all 6
      cases. CONCLUSION: The novel acquisition in this work allows the measurement of
      histologically relevant physical parameters, such as the relative proportions of
      vascular spaces. In the placenta, this may help us to better understand the
      physiological properties of the tissue in disease.

PMID- 30239037
TI  - IL-4 dysregulates microRNAs involved in inflammation, angiogenesis and apoptosis
      in epidermal keratinocytes.
AB  - IL-4 plays an important role in the pathogenesis of atopic dermatitis (AD) by
      dysregulating many key factors at the transcriptional level. In this study, a
      microRNA array technique and IL-4 transgenic mice were used to demonstrate that
      IL-4 dysregulates microRNAs involved in inflammation, angiogenesis,
      lymphangiogenesis and apoptosis. Of the 372 common microRNAs examined, 26 and one
      microRNAs were found to be up- and down-regulated, respectively. MicroRNA-101-5p,
      -122-5p, -142-3p, -204-5p, -335-3p, -376a-3p, -378a-5p, -639 and -9-5p are among
      the most significantly up-regulated microRNAs. MicroRNA-147a, the only one that
      was down- regulated in the present study, attenuates TLR-induced inflammatory
      responses. These dysregulated microRNAs may provide post-transcriptional
      regulation of key genes in AD.

PMID- 30239038
TI  - The impact of age on cardiac electromechanical function in asymptomatic
      individuals.
AB  - BACKGROUND AND AIM: Whether aging affects left ventricular (LV) filling and
      ejection and the LV electric function is not well established. We investigated
      the effect of normal aging on echocardiographic measurements of LV morphology and
      function, LV electric function and the relationship between LV electric and
      mechanical function in asymptomatic individuals. METHODS: As part of a cross
      sectional survey for the prevalence of coronary risk factors in the general
      population in Caltanissetta, Italy, individuals without signs or symptoms of
      coronary artery disease or heart failure were randomly selected and underwent
      electrocardiographic and echocardiographic examination. QRS duration and
      amplitude, PR, QT and QTc intervals, were automatically measured.
      Echocardiographic examination included the measurement of LV systolic and
      diastolic dimensions, volumes and ejection fraction (EF). From the spectral
      Doppler flow LV early diastolic (E wave) and atrial systolic (A wave) velocities,
      isovolumic relaxation time (IVRT) and isovolumic contraction time (IVCT) were
      measured. Global LV dyssynchrony was assessed using the total isovolumic time (T
      IVT) and the Tei index. RESULTS: Aging reduced LV long-axis function, LV filling
      time and E wave velocity and prolonged T-IVT, IVRT and Tei index. It did not
      affect LV dimensions, ejection fraction, IVCT or QRS amplitude and duration. QRS
      duration correlated with LV dimensions, wall thickness and left atrial area. QRS
      amplitude and QTc interval correlated with the markers of LV dyssynchrony T-IVT
      and Tei index. CONCLUSIONS: Overall, systolic and electric LV function are not
      affected by age, whereas subendocardial function, diastolic and synchronous
      function are significantly influenced.

PMID- 30239039
TI  - Characterizing toxicity of metal-contaminated sediments from the Upper Columbia
      River, Washington, USA, to benthic invertebrates.
AB  - Sediments from the Upper Columbia River, Washington, USA, are contaminated with
      metals from smelting operations. We conducted short-term and long-term tests with
      the midge Chironomus dilutus and the amphipod Hyalella azteca and short-term
      tests with the freshwater mussel Lampsilis siliquoidea with 54 sediments from the
      Upper Columbia River to characterize thresholds for toxicity of metals to benthic
      invertebrates. Test sediments were screened for toxicity by comparisons with low
      metal reference sediments. Toxic effects on amphipods occurred primarily in
      sediments from the upstream (riverine) reach, and toxic effects on midges
      occurred in sediments from both the upstream reach and the downstream (reservoir)
      reach. Little toxicity was observed in mussel tests. Toxicity thresholds (20%
      effect concentrations [EC20s]) for metals in sediment and porewater were
      estimated from logistic concentration-response models. Copper (Cu) concentrations
      in the simultaneously extracted metal fraction of sediments and bioavailable Cu
      in porewater, as characterized by biotic ligand models, had consistent
      associations with toxicity endpoints. Concentration-response models for sediment
      Cu produced EC20s for 6 endpoints, with long-term amphipod survival and
      reproduction being the most sensitive. A logistic regression model fitted to an
      endpoint sensitivity distribution for sediment Cu predicted that approximately
      one-half of the sediments tested would be toxic to at least one endpoint and that
      approximately 20% of test sediments would be toxic to more than half of the
      endpoints. These results indicate that sediments from the upstream reach of the
      Upper Columbia River, which contain high concentrations of metals associated with
      slags, cause a wide range of toxic effects in laboratory tests and are likely to
      have adverse effects on benthic invertebrate communities. Environ Toxicol Chem
      2018;37:3102-3114. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This
      article is a US government work and, as such, is in the public domain in the
      United States of America.

PMID- 30239040
TI  - Conventional dialysis in the elderly: How lenient should our guidelines be?
AB  - There has been a dramatic, worldwide expansion in life expectancy across the last
      century. This has resulted in a progressively more elderly and comorbid
      population. It is increasingly recognized that healthcare in this group needs to
      move to the concept of "adding life to years". Recognition and assessment of
      frailty is vital in changing our approach in elderly patients. Current guidelines
      in dialysis have a limited evidence base across all age groups, but particularly
      the elderly and serve them poorly. Moreover, the burden of guidelines for each
      comorbidity of the multimorbid patient is increasing and can be conflicting.
      Finally, there is increasing evidence relating to the harm associated with the
      delivery of conventional dialysis. In dialysis patients, frailty is the
      overwhelming determinant in relation to patient-specific outcomes rather than
      modality of treatment; therefore, the focus should be on promoting quality of
      life. We need to focus on new priorities of care when we design guidelines "for
      people not diseases". Patient-centered goal-directed therapy, arising from shared
      decision making between physician and patient, should allow adaption of the
      dialysis regime to maximize opportunities while minimizing treatment-related
      morbidity and concentrating on alleviating symptoms.

PMID- 30239041
TI  - Dissipative Self-Assembly of Anisotropic Nanoparticle Chains with Combined
      Electrodynamic and Electrostatic Interactions.
AB  - Dissipative self-assembly of colloidal nanoparticles offers the prospect of
      creating reconfigurable artificial materials and systems, yet the phenomenon only
      occurs far from thermodynamic equilibrium. Therefore, it is usually difficult to
      predict and control. Here, a dissipative colloidal solution system, where
      anisotropic chains with different interparticle separations in two perpendicular
      directions transiently arise among largely disordered silver nanoparticles
      illuminated by a laser beam, is reported. The optical field creates a
      nonequilibrium dissipative state, where a disorder-to-order transition occurs
      driven by anisotropic electrodynamic interactions coupled with electrostatic
      interactions. Investigation of the temporal dynamics and spatial arrangements of
      the nanoparticle system shows that the optical binding strength and entropy of
      the system are two crucial parameters for the formation of the anisotropic chains
      and responsible for adaptive behaviors, such as self-replication of dimer units.
      Formation of anisotropic nanoparticle chains is also observed among colloidal
      nanoparticles made from other metal (e.g., Au), polymer (e.g., polystyrene),
      ceramic (e.g., CeO2 ), and hybrid materials (e.g., SiO2 @Au core-shell),
      suggesting that light-driven self-organization will provide a wide range of
      opportunities to discover new dissipative structures under thermal fluctuations
      and build novel anisotropic materials with nanoscale order.

PMID- 30239042
TI  - Closing the Loop: Triazolylpyridine Coordination Drives the Self-Assembly of
      Metallomacrocycles with Tunable Topologies for Small-Molecule and Guanine
      Quadruplex Recognition.
AB  - The 2-(1,2,3-triazol-4-yl)pyridine motif, with its facile "click" synthesis and
      remarkable coordinative properties, is an attractive chelate for applications in
      the metal-directed self-assembly of intricate three-dimensional structures.
      Organic ligands that bear two such chelates bridged by flexible hinge moieties
      readily undergo self-assembly with metal ions of different coordination
      geometries to generate a series of topologically diverse metallomacrocycles that
      can be used for numerous applications. Herein, the synthesis and self-assembly of
      one such ligand with zinc(II), copper(II), and palladium(II) ions is reported,
      and the stability of the resulting metallomacrocycles described. An investigation
      into the use of these metallomacrocycles for the recognition of both small
      molecule substrates, such as deoxyguanosine monophosphate, and larger biological
      assemblies, such as DNA and RNA guanine quadruplexes, is also described.

PMID- 30239043
TI  - Dynamic Electronic Doping for Correlated Oxides by a Triboelectric Nanogenerator.
AB  - The metal-insulator transition of vanadium dioxide (VO2 ) is exceptionally
      sensitive to charge density and electron orbital occupancy. Thus three-terminal
      field-effect transistors with VO2 channels are widely adopted to control the
      phase transition by external gating voltage. However, current leakage, electrical
      breakdown, or interfacial electrochemical reactions may be inevitable if
      conventional solid dielectrics or ionic-liquid layers are used, which possibly
      induce Joule heating or doping in the VO2 layer and make the voltage-controlled
      phase transition more complex. Here, a triboelectric nanogenerator (TENG) and a
      VO2 film are combined for a novel TENG-VO2 device, which can overcome the
      abovementioned challenges and achieve electron-doping-induced phase modulation.
      By taking advantage of the TENG structure, electrons can be induced in the VO2
      channel and thus adjust the electronic states of the VO2 , simultaneously. The
      modulation degree of the VO2 resistance depends on the temperature, and the major
      variation occurs when the temperature is in the phase-transition region. The
      accumulation of electrons in the VO2 channel also is simulated by finite element
      analysis, and the electron doping mechanism is verified by theoretical
      calculations. The results provide a promising approach to develop a novel type of
      tribotronic transistor and new electronic doping technology.

PMID- 30239044
TI  - An Insight into the Phase Transformation of WS2 upon Fluorination.
AB  - The transformation from semiconducting to metallic phase, accompanied by a
      structural transition in 2D transition metal dichalcogenides has attracted the
      attention of the researchers worldwide. The unconventional structural
      transformation of fluorinated WS2 (FWS2 ) into the 1T phase is described. The
      energy difference between the two phases debugs this transition, as fluorination
      enhances the stability of 1T FWS2 and makes it energetically favorable at higher
      F concentration. Investigation of the electronic and optical nature of FWS2 is
      supplemented by possible band structures and bandgap calculations. Magnetic
      centers in the 1T phase appear in FWS2 possibly due to the introduction of defect
      sites. A direct consequence of the phase transition and associated increase in
      interlayer spacing is a change in friction behavior. Friction force microscopy is
      used to determine this effect of functionalization accompanied phase
      transformation.

PMID- 30239045
TI  - Biomineralization as a Paradigm of Directional Solidification: A Physical Model
      for Molluscan Shell Ultrastructural Morphogenesis.
AB  - Molluscan shells are a model system to understand the fundamental principles of
      mineral formation by living organisms. The diversity of unconventional mineral
      morphologies and 3D mineral-organic architectures that comprise these tissues, in
      combination with their exceptional mechanical efficiency, offers a unique
      platform to study the formation-structure-function relationship in a
      biomineralized system. However, so far, morphogenesis of these ultrastructures is
      poorly understood. Here, a comprehensive physical model, based on the concept of
      directional solidification, is developed to describe molluscan shell
      biomineralization. The capacity of the model to define the forces and
      thermodynamic constraints that guide the morphogenesis of the entire shell
      construct-the prismatic and nacreous ultrastructures and their transitions-and
      govern the evolution of the constituent mineralized assemblies on the
      ultrastructural and nanostructural levels is demonstrated using the shell of the
      bivalve Unio pictorum. Thereby, explicit tools for novel bioinspired and
      biomimetic bottom-up materials design are provided.

PMID- 30239046
TI  - Somatic mutational profiles of stage II and III gastric cancer according to tumor
      microenvironment immune type.
AB  - We aimed to determine somatic mutational profiles of stage II/III gastric cancers
      (GCs) according to their tumor microenvironment immune types (TMITs), which
      classify cancer based on co-assessment of PD-L1 expression and CD8+ tumor
      infiltrating lymphocytes. Eighty patients with stage II/III GC were classified as
      follows: TMIT I (PD-L1+ /CD8High ), TMIT II (PD-L1- /CD8Low ), TMIT III (PD-L1+
      /CD8Low ), and TMIT IV (PD-L1- /CD8High ). Deep targeted sequencing using a panel
      of 170 cancer-related genes was performed on an Illumina HiSeq-2500 system. Most
      frequently mutated genes included GNAQ (41.3%), TP53 (38.8%), CREBBP (35.0%), and
      MAP3K1 (35.0%). PIK3CA mutations were observed more frequently in TMIT I (45.8%)
      and III (66.7%), than in II (12.0%) and IV (8.0%). Other genes with enriched
      mutations within TMIT I included ATM (33.3%), BRCA2 (33.3%), MAP3K4 (29.2%), and
      FLT4 (25.0%). FGFR3, MAP3K1, and RUNX1 mutations were more frequently found in
      TMIT II. TMIT III had a unique somatic mutation profile harboring enriched
      mutations of histone modifiers including CREBBP and KMT2A, and we found FGFR2
      amplification exclusively within TMIT IV. Fuzzy clustering analysis based on
      somatic mutation frequencies identified a hypermutated group (cluster 1) and a
      hypomutated group (cluster 2). Cluster 1 had significant associations with TMIT
      I, EBV+ GCs, and MSI-H GCs (P = .023, .014, and .004), and had better overall
      survival (P = .057) than Cluster 2. TMIT I, EBV+ , and MSI-H GCs were estimated
      to have greater tumor mutational burden (P = .023, .003, and .015). By analyzing
      somatic mutation profiles according to TMIT classification, we identified TMIT
      specific genetic alterations that provide clues for biological linkage between GC
      genetics and microenvironment.

PMID- 30239047
TI  - Interleukin-7 gene polymorphism rs766736182 associates with the risk of asthma in
      children.
AB  - BACKGROUND: Recently studies uncovered associations between polymorphisms of
      interleukin genes and the risk of asthma. However, the relationship between
      polymorphisms of interleukin-7 gene and the risk of children asthma has not been
      discovered yet. This study aims to investigate the relationship between single
      nucleotide polymorphisms (SNPs) on interleukin-7 gene and the risk of children
      asthma. METHODS: We genotyped eight SNPs of interleukin-7 gene in blood samples
      from 437 asthma patients and 489 healthy controls to analyze potential
      associations of these SNPs with the risk of asthma in children. RESULTS: A
      missense SNP rs766736182 (odds ratio (OR) = 2.185, 95% confidence interval (CI) =
      1.561-2.252, P-value = 8.69468E-19) of the interleukin-7 gene is associated with
      the risk of children asthma. CONCLUSIONS: This study reveals that SNP rs766736182
      of interleukin-7 is the risk factor for children asthma and implies potential
      role of immune system in the pathogenesis of children asthma.

PMID- 30239049
TI  - Nuclear transglutaminase 2 directly regulates expression of cathepsin S in rat
      cortical neurons.
AB  - Transglutaminase 2 (TG2) is a protein that modulates neuronal survival processes.
      Although TG2 is primarily cytosolic, data have suggested the nuclear localization
      of TG2 is strongly associated with neuronal viability. Depletion of TG2 in
      neurons results in neurite retraction and loss of viability, which is likely due
      to a dysregulation in gene expression. To begin to understand how TG2 regulates
      neuronal gene expression, chromatin immunoprecipitation was performed in neurons
      with TG2 overexpression. The resulting genomic DNA was recovered and sequenced.
      Bioinformatics analyses revealed that a signature DNA motif was enriched in the
      TG2 immunoprecipitated genomic DNA. In particular, this motif strongly mapped to
      a region proximate to the gene Ctss (cathepsin S). Knockdown of TG2 resulted in a
      significant increase in cathepsin S expression, which preceded the loss of
      neuronal viability. This is the first demonstration that TG2 directly associates
      with genomic DNA and regulates gene expression in neurons. Given that expression
      of cathepsin S is increased in neurological disease states, our data suggest that
      TG2 may play a role in promoting neuron health in part by repressing the
      expression of cathepsin S. Overall these data provide new insights into the
      function of nuclear TG2 in neurons.

PMID- 30239048
TI  - Predominance of hypoechoic tissue changes in nine dogs with malignant prostatic
      lymphoma.
AB  - Neoplasia of the prostate is relatively uncommon in dogs with adenocarcinoma
      being the most common type. Non-epithelial tumors are rare and only individual
      cases of malignant lymphoma affecting the prostate have been reported. The
      purpose of this multi-institutional, retrospective, descriptive study was to
      characterize the ultrasonographic features of canine prostatic lymphoma.
      Inclusion criteria were an abdominal ultrasound and cytological/histological
      diagnosis of malignant prostatic lymphoma. Ultrasonographic features were
      recorded based on the original ultrasonographic reports and consensus opinion of
      two readers on the available image sets retrospectively. Nine dogs met the
      inclusion criteria with a mean age of 6.5 years. Seven dogs were intact and two
      neutered. Subjective prostatomegaly was noted in all patients however not
      reproducible by objective measurements. Altered shape with rounded/irregular
      margins was detected in 78% of the cases. All prostates presented either diffuse
      (three dogs) or focal/periurethral (four dogs) and/or multifocal areas of
      hypoechogenicity (three dogs). In one dog, focal and multifocal hypoechoic
      changes co-occurred. Prostatic mineralization was not present in any of the
      cases. Ultrasonographic features of infiltrative disease of multiple organs
      and/or lymphadenopathy was found in all cases. Even though malignant lymphoma is
      rare in the prostate, it should be included in the list of differentials in
      patients with hypoechoic lesions/areas, altered shape, lack of mineralization of
      the prostatic parenchyma and evidence of multiorgan involvement.

PMID- 30239050
TI  - Ulnar ostectomy decreases the stability of canine cadaver carpi as assessed with
      stress radiography.
AB  - Distal ulnar ostectomy may be performed palliatively in patients with distal
      ulnar osteosarcoma. Concurrent arthrodesis of the carpus has been proposed to
      counteract joint instability following transection of carpal ligaments associated
      with removal of the distal ulna. The objective of this prospective one group
      pretest, posttest study was to assess stability of the carpus following distal
      ulnar ostectomy using pre- and postoperative stress radiographic views in a group
      of canine cadaver limbs. Seven thoracic limbs from six canine cadavers weighing
      more than 20 kg were obtained. Lateral and dorsopalmar, extended lateral, medial
      stress, and lateral stress radiographs were made before and after distal ulnar
      ostectomy. Presurgical canine cadaver carpal angle measurements were as follows
      (mean +/- standard deviation): extension 205.9 degrees  +/- 5.4; medial stress
      25.1 degrees  +/- 5.7; and lateral stress 13.3 degrees  +/- 5.2 degrees . Cadaver
      limb joint angles exceeded those previously reported in live dogs. A significant
      increase in carpal angle was noted following ulnar ostectomy. The mean increases
      in carpal angle were as follows: (mean +/- standard deviation (95% confidence
      interval)): extension 6.2 degrees  +/- 4.9 (2.6-9.8) (P = 0.007); medial stress
      3.2 degrees  +/- 3.0 (1.0-5.5) (P = 0.015); lateral stress 6.2 degrees  +/- 5.2
      (2.4-10.1) (P = 0.010). Findings from this cadaver study support the use of
      supplementary stabilization for clinical patients undergoing distal ulnar
      ostectomy. Future studies are needed in clinical patients to evaluate changes in
      limb positioning and gait associated with distal ulnar ostectomy.

PMID- 30239051
TI  - Blood routine test is a good indicator for predicting premature rupture of
      membranes.
AB  - OBJECTIVE: To assess the value of blood routine test (blood RT) in order to
      predict the occurrence of premature rupture of membranes (PROM). METHODS: A
      retrospective study was conducted to collect blood RT data from 100 cases of
      preterm premature rupture of membranes (pPROM), 70 cases of full-term premature
      rupture of membranes (fPROM), and 100 cases of full-term pregnancy (Normal).
      Nonparametric tests were performed for each blood routine parameter, the ROC
      curve was established for the parameters with significant difference, and the
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), positive likelihood ratios (+LR), and negative likelihood ratios (
      LR) were further calculated. RESULTS: The statistical results showed that WBC,
      NE.%, LY.%, EO.%, BA.%, NE.#, EO.#, RBC, HGB, HCT, and NLR were significantly
      different between pPROM and fPROM (P < 0.05). There was a significant difference
      in WBC, NE.%, LY.%, NE.#, MO.#, RBC, HGB, HCT, and NLR between the pPROM and
      Normal groups (P < 0.05). Between the fPROM and Normal groups, only WBC was
      statistically significant (P < 0.05). By establishing ROC curve, the results
      showed that when the cutoff value of WBC was 9.63 and NEU# was 7.12, their
      combined detection had the best predictive value with a sensitivity of 73% and a
      specificity of 81%. In addition, Its PPV was 79.3%, NPV was 75%, +LR was 3.84,
      and -LR was 0.33. CONCLUSION: The patient's blood RT results can be used to
      predict the risk of premature rupture of membranes, and in order to improve the
      sensitivity and specificity, multiple parameters can be combined.

PMID- 30239053
TI  - How much does birth weight matter for child health in developing countries?
      Estimates from siblings and twins.
AB  - About 200 million children globally are not meeting their growth potential, and
      as a result will suffer the consequences in terms of future outcomes. I examine
      the effects of birth weight on child health and growth using information from 66
      countries. I account for missing data and measurement error using instrumental
      variables and adopt an identification strategy based on siblings and twins. I
      find a consistent effect of birth weight on mortality risk, stunting, wasting,
      and coughing, with some evidence for fever, diarrhoea, and anaemia. Bounds
      analysis indicates that coefficients may be substantially underestimated due to
      mortality selection. Improving the pre-natal environment is likely to be
      important for helping children reach their full potential.

PMID- 30239052
TI  - Canine and feline abdominal arterioportal communications can be classified based
      on branching patterns in computed tomographic angiography.
AB  - Arterioportal vascular anomalies are communications between the splanchnic
      arteries and the portal system that represent a rare cause of presinusoidal
      portal hypertension in small animals. There is little information concerning the
      imaging findings of arterioportal communications in small animals and no
      classification could be found for radiologists and surgeons. The aims of this
      retrospective descriptive multicentric study were to describe the computed
      tomographic characteristics of arterioportal communications in a group of cats
      and dogs, and to propose a classification based on computed tomography (CT)
      angiographic anatomy. Computed tomography databases from multiple veterinary
      hospitals were searched for cats and dogs with a diagnosis of arterioportal
      communication. A total of 36 animals (33 dogs, three cats) met the inclusion
      criteria. There were 32 intrahepatic arterioportal malformations and four
      extrahepatic fistulae. The intrahepatic arterioportal malformations were
      classified as right divisional (11/32) and left divisional (21/32), and the left
      divisional were subclassified as left medial (16/21) and left lateral (4/21). One
      patient showed multiple intrahepatic arterioportal communications with
      concomitant left medial and left lateral conformations. Two patients with
      intrahepatic arteriovenous malformation showed concomitant congenital
      intrahepatic shunts. The proposed anatomical classification based on CT
      angiography could allow veterinary radiologists to have a more systematic
      approach and help improve the radiologist-surgeon communication.

PMID- 30239054
TI  - Emerging Structural Biology of Lipid G-Protein Coupled Receptors.
AB  - The first crystal structure of a G Protein-Coupled Receptor (GPCR) was that of
      the bovine rhodopsin, solved in 2000, and is a light receptor within retina rode
      cells that enables vision by transducing a conformational signal from the light
      induced isomerization of retinal covalently bound to the receptor. More than
      seven years after this initial discovery and following more than twenty years of
      technological developments in GPCR expression, stabilization, and
      crystallography, the high-resolution structure of the adrenaline binding beta2 
      adrenergic receptor, a ligand diffusible receptor, was discovered. Since then,
      high-resolution structures of more than 53 unique GPCRs have been determined
      leading to a significant improvement in our understanding of the basic mechanisms
      of ligand-binding and ligand-mediated receptor activation that revolutionized the
      field of structural molecular pharmacology of GPCRs. Recently, several structures
      of eight unique lipid-binding receptors, one of the most difficult GPCR families
      to study, have been reported. This review presents the outstanding structural and
      pharmacological features that have emerged from these new lipid receptor
      structures. The impact of these findings goes beyond mechanistic insights,
      providing evidence of the fundamental role of GPCRs in the physiological
      integration of the lipid signaling system, and highlighting the importance of
      sustained research into the structural biology of GPCRs for the development of
      new therapeutics targeting lipid receptors. This article is protected by
      copyright. All rights reserved.

PMID- 30239055
TI  - Facilitators and inhibitors of transition for older people who have relocated to
      a long-term care facility: A systematic review.
AB  - Moving into a long-term care facility to live permanently is a significant life
      event for older people. Care facilities need to support older people to make a
      healthy transition following relocation. To help achieve this, we need to
      understand what facilitates and inhibits the transition process from the
      perspective of older people, their families, and care facility staff. Our review
      generated new knowledge to inform this understanding. We addressed the question:
      what factors facilitate and inhibit transition for older people who have
      relocated to a long-term care facility? Five electronic databases, PsychINFO,
      British Nursing Index, CINAHL, MEDLINE and Web of Science were searched for the
      period January 1990 to October 2017. Grey literature searches were conducted
      using Google Scholar, and Social Science Research Network. Data were extracted
      for individual studies and a narrative synthesis was conducted informed by
      Meleis's Theory of Transition. Thirty-four studies (25 qualitative, 7
      quantitative and 2 mixed methods) met the inclusion criteria. Data synthesis
      identified that transition following relocation was examined using a variety of
      terms, timelines and study designs. Potential personal and community focused
      facilitators and inhibitors mapped to four themes: resilience of the older
      person, interpersonal connections and relationships, this is my new home, and the
      care facility as an organisation. These findings can inform the development of
      interventions for these target areas. They highlight also that further research
      is warranted to understand the organisational culture of long-term care
      facilities, how this influences transition, and how it might be shaped to create
      and sustain a caring culture for older people.

PMID- 30239056
TI  - Predictive factors of treatment adherence in cancer outpatients.
AB  - OBJECTIVE: Identify which variables are predictors of treatment adherence in
      cancer patients. METHODS: Two hundred twenty cancer outpatients were evaluated by
      the following instruments: questionnaire on sociodemographic and clinical data,
      NEO-FFI Personality Inventory Revised (NEO-FFI-R), Multidimensional Health Locus
      of Control (MHLC) scale, Hospital Anxiety and Depression Scale (HADS), patient's
      knowledge about cancer disease questionnaire, and Adherence Determinants
      Questionnaire (ADQ). A logistic regression analysis was applied to verify the
      predictive power of the variables, and network analyses were conducted through
      the qgraph package. RESULTS: The sample was composed of 138 (62.7%) women and 82
      (37.3%) men. The mean age of participants was 54.66 (SD = 13.30), and the
      education level mean was 8.32 (DP = 3.76) years of study. Powerful others locus
      of control (LOC) and the personality factors conscientiousness and agreeableness
      are presented as predictors of high treatment adherence. The variable family
      cancer history, on the other hand, was a predictor of lower adherence levels.
      CONCLUSIONS: The powerful others LOC may be connected with more trust and
      dependence in the health team, leading to better adherence. Specific
      characteristics of personality factors can help individuals to cooperate with
      their caregivers and to follow medical orders. The evaluated factors are
      interrelated and should be taken into account by health professionals when
      developing interventions to modify health-related behaviors and treatment
      adherence.

PMID- 30239059
TI  - Psychometric properties of the Clinical Outcome Routine Evaluation-Learning
      Disabilities 30-Item (CORE-LD30).
AB  - BACKGROUND: There is paucity in availability of valid and reliable measures of
      psychopathology that can be routinely applied with an intellectual disability
      (ID) population in clinical practice. The psychometric properties of the Clinical
      Outcome Routine Evaluation-Learning Disabilities 30-Item version (CORE-LD30) are
      examined. METHOD: The CORE-LD30 was administered to 271 sequential referrals to
      three National Health Service (NHS) ID services providing psychological support.
      A principal components analysis with oblique rotation was conducted with
      examination of convergent validity for extracted domains. RESULTS: Three rotated
      factors were extracted with good levels of internal consistency reported for the
      overall measure (alpha = 0.92) and each of the domains, conceptually labelled
      Problems/Symptoms (alpha = 0.90), Risk to Self (alpha = 0.76) and Risk to Others
      (alpha = 0.71). Convergent validity is reported for two domains
      [Problems/Symptoms with the Glasgow Depression Scale for people with a learning
      disability (LD) and Risk to Others with the Health of the Nation Outcome Scale
      LD], and support for the CORE-LD30 as a 'core' measure indicated. CONCLUSIONS:
      The CORE-LD30 is recommended as a useful broad ranging measure of psychopathology
      for use with an ID population. Domains may prove to be useful for research and
      clinical purposes. Further research is recommended to examine the ability to
      monitor clinical change associated with specific levels of presentation and
      different clinical presentations/cohorts.

PMID- 30239057
TI  - BSACI guideline for the diagnosis and management of allergic and non-allergic
      rhinitis (Revised Edition 2017; First edition 2007).
AB  - This is an updated guideline for the diagnosis and management of allergic and non
      allergic rhinitis, first published in 2007. It was produced by the Standards of
      Care Committee of the British Society of Allergy and Clinical Immunology, using
      accredited methods. Allergic rhinitis is common and affects 10-15% of children
      and 26% of adults in the UK, it affects quality of life, school and work
      attendance, and is a risk factor for development of asthma. Allergic rhinitis is
      diagnosed by history and examination, supported by specific allergy tests.
      Topical nasal corticosteroids are the treatment of choice for moderate to severe
      disease. Combination therapy with intranasal corticosteroid plus intranasal
      antihistamine is more effective than either alone and provides second line
      treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy
      is highly effective when the specific allergen is the responsible driver for the
      symptoms. Treatment of rhinitis is associated with benefits for asthma. Non
      allergic rhinitis also is a risk factor for the development of asthma and may be
      eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non
      allergic rhinitis may be a presenting complaint for systemic disorders such as
      granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis
      can be caused by viruses, and less commonly by bacteria, fungi and protozoa.

PMID- 30239058
TI  - Improving the estimation of prognosis for glioblastoma patients by MR based
      hemodynamic tissue signatures.
AB  - Advanced MRI and molecular markers have been raised as crucial to improve
      prognostic models for patients having glioblastoma (GBM) lesions. In particular,
      different MR perfusion based markers describing vascular intrapatient
      heterogeneity have been correlated with tumor aggressiveness, and represent key
      information to understand tumor resistance against effective therapies of these
      neoplasms. Recently, hemodynamic tissue signature (HTS) markers based on MR
      perfusion images have been demonstrated to be useful for describing the
      heterogeneity of GBM at the voxel level, as well as demonstrating significant
      correlations with the patient's overall survival. In this work, we analyze the
      abilities of these markers to improve the conventional prognostic models based on
      clinical, morphological, and demographic features. Our results, in both the
      regression and classification tests, show that inclusion of the HTS markers
      improves the reliability of prognostic models. The HTS method is fully automatic
      and it is available for research use at http://www.oncohabitats.upv.es.

PMID- 30239060
TI  - Preparation of Siloxane-Based Microporous Crystals from Hydrogen-Bonded Molecular
      Crystals of Cage Siloxanes.
AB  - Controlled assembly of siloxane-based building blocks provides a rational
      approach toward designed architectures of silica-based porous materials. Here, a
      non-hydrothermal method to prepare microporous crystals from cage-type
      oligosiloxanes is reported. The crystals formation occurs through an ordered
      assembly assisted by hydrogen bonds and subsequent intermolecular connection by
      silylation. Cage siloxanes with a double-four ring (D4R) structure were modified
      with dimethylsilanol groups. Intermolecular hydrogen bonding of the
      dimethylsilanol groups led to the formation of a pillared-layer structure
      consisting of D4R units. A new crystalline microporous material retaining the
      original ordered arrangement was realized by bridging adjacent cages within the
      crystals by direct silylation of the silanol groups with trichlorosilane. The use
      of this silylating agent created microporous crystals containing Si-H groups,
      proving the advantages of the proposed concept.

PMID- 30239061
TI  - Antiplatelet and anticoagulant activities of two phospholipase A2s purified from
      Cerastes cerastes venom: Structure-function relationship.
AB  - This study aimed to elucidate anticoagulant/antiplatelet mechanisms of two
      previously purified PLA2 s from Cerastes cerastes venom, here, termed Cc1 -PLA2
      and Cc2 -PLA2 . Both PLA2 s present close molecular weights of 13,534 and 13,430
      Da and Isoectric pH (pI) 7.38 and 7.86 respectively, for Cc1 -PLA2 and Cc2 -PLA2
      . These Ca2+ -dependent enzymes showed a high catalytic activity upon
      phospholipids, inducing indirect hemolysis, since they conserve the catalytic
      domain of PLA2 s 26 CYCGWGGKG34 . They exhibited dual inhibition of platelet
      aggregation by targeting P2 Y12 and TPalpha receptors preventing Adenosine
      diphosphate/arachidonate binding and blood clotting. These effects are due to the
      interaction of Cc1 -PLA2 s/Cc2 -PLA2 s with factor FXa through a noncatalytic PL
      independent mechanism leading to nonreleased thrombin. Both proteins consist of
      120 amino acid residues and share similar three-dimensional structures close to
      other SV-PLA2 s. Structural data of PLA2 s allowed the relevant residues involved
      in binding to FXa and platelet receptors. These findings may lead to the design
      of novel noncompetitive FXa inhibitors.

PMID- 30239062
TI  - The hepcidin-25/erythroferrone ratio predicts improvement of anemia in
      hemodialysis patients treated with ferric citrate hydrate.
AB  - BACKGROUND/AIMS: Hepcidin-25 (HEP-25) and erythroferrone (ERFE) are key
      regulators of iron homeostasis. Correlations among serum ferritin, ERFE, and HEP
      25 levels and improvements in anemia have not been evaluated after administration
      of ferric citrate hydrate (FCH). METHODS: This retrospective observational study
      investigated 24 patients on hemodialysis with both anemia (hemoglobin [Hb] < 12
      g/dL) and hyperphosphatemia (inorganic phosphorus >= 6 mg/dL). The patients who
      were administered FCH (1,500 mg/day) for 12 consecutive weeks and 12 control
      patients who were administered a phosphate binder other than FCH were included.
      Correlations among Hb, HEP-25, and ERFE levels were studied. We then stratified
      the FCH group into two subgroups using the median baseline values of ferritin,
      HEP-25, ERFE, and HEP-25/ERFE ratio to predict whether these markers could serve
      as prognostic indicators in the treatment of anemia. RESULTS: In the FCH group,
      Hb, transferrin saturation (TSAT), ferritin, HEP-25, and ERFE levels were all
      significantly increased, while inorganic phosphorus levels, dosage of
      erythropoietin-stimulating agent, and erythropoietin resistance index were all
      significantly decreased after drug administration. A significant inverse
      correlation was apparent between Hb and HEP-25 levels, and a significant positive
      correlation was seen between Hb and ERFE levels. A significant inverse
      correlation was found between HEP-25 and serum ERFE levels. Compared with the
      high HEP-25/ERFE ratio group, only the low HEP-25/ERFE ratio group exhibited
      significantly increased Hb levels at 12 weeks. CONCLUSIONS: HEP-25/ERFE ratio
      could be a novel prognostic marker for increases in Hb levels following FCH
      administration. This article is protected by copyright. All rights reserved.

PMID- 30239063
TI  - Feasibility of methylome analysis using small amounts of genomic DNA from
      formalin-fixed paraffin-embedded tissue.

PMID- 30239064
TI  - Renal genetics in Australia: Kidney medicine in the genomic age.
AB  - There have been few new therapies for patients with chronic kidney disease in the
      last decade. However, the management of patients affected by genetic kidney
      disease is rapidly evolving. Inherited or genetic kidney disease affects around
      10% of adults with end-stage kidney disease and up to 70% of children with early
      onset kidney disease. Advances in next-generation sequencing have enabled rapid
      and cost-effective sequencing of large amounts of DNA. Next-generation sequencing
      based diagnostic tests now enable identification of a monogenic cause in around
      20% of patients with early-onset chronic kidney disease. A definitive diagnosis
      through genomic testing may negate the need for prolonged diagnostic
      investigations and surveillance, facilitate reproductive planning and provide
      accurate counselling for at-risk relatives. Genomics has allowed the better
      understanding of disease pathogenesis, providing prognostic information and
      facilitating development of targeted treatments for patients with inherited or
      genetic kidney disease. Although genomic testing is becoming more readily
      available, there are many challenges to implementation in clinical practice.
      Multidisciplinary renal genetics clinics serve as a model of how some of these
      challenges may be overcome. Such clinics are already well established in most
      parts of Australia, with more to follow in future. With the rapid pace of new
      technology and gene discovery, collaboration between expert clinicians,
      laboratory and research scientists is of increasing importance to maximize
      benefits to patients and health-care systems.

PMID- 30239065
TI  - Beyond the phonological deficit: Semantics contributes indirectly to decoding
      efficiency in children with dyslexia.

PMID- 30239066
TI  - The management of pseudomyogenic hemangioendothelioma of the foot: A case report
      and review of the literature.
AB  - Pseudomyogenic hemangioendothelioma (PMH) is a rare, mostly indolent, endothelial
      neoplasm of low-grade malignancy, often mimicking myoid and epithelioid tumors
      histologically. It is more frequent in young adult males and it usually presents
      with multiple cutaneous nodules, mostly localized at the extremities. It
      traverses several tissue planes simultaneously and can involve dermis, subcutis,
      skeletal muscle, and bone. Histologically, it is characterized by plump spindle
      cells with eosinophilic cytoplasm, often arranged in fascicles and epithelioid
      cells with "pseudomyogenic" morphology. Immunohistochemically, PMH is positive
      for Factor VIII, FLI-1, INI-1, vimentin, MDM2, CDK4, CD31, AE1/AE3, EMA, and P63.
      The efficacy of treatments is only partially known. Because of the frequent
      multifocal aspect of PMH, which contraindicates surgery, systemic treatments,
      such as gemcitabine, sirolimus, and everolimus are used. Based on our observation
      of multifocal PMH of the foot in a 17-year-old male patient, treated with
      gemcitabine with complete cutaneous response in a 2-year follow-up, we decided to
      discuss this rare tumor and underline its progression and therapeutic approaches.
      Thanks to a correct diagnosis, it is possible to avoid aggressive therapeutic
      approaches, which would be necessary for nonindolent diseases, such as sarcoma,
      which often needs amputation.

PMID- 30239068
TI  - Step-counting accuracy of activity monitors in persons with Down syndrome.
AB  - BACKGROUND: Accelerometers and pedometers have been used to monitor the number of
      steps. However, the evidence on the step-counting accuracy of these devices -
      especially accelerometers - is limited in persons with Down syndrome (DS). This
      study therefore examined the accuracy of accelerometers placed on the hip or
      wrist and of a pedometer with a uni-axial accelerometer mechanism in measuring
      steps in persons with DS and whether device error is associated with walking
      speed, height, weight, body mass index, waist circumference, leg length, age or
      sex. METHOD: Seventeen persons with DS (eight women and nine men; age 33 +/- 15
      years) walked over-ground for 6 min at their preferred speed. The steps were
      measured with a hip-worn and a wrist-worn ActiGraph accelerometer using the
      manufacturer's default (DF) and low-frequency extension (LFE) filters, and with
      the NL-1000 New Lifestyles pedometer on the hip. Steps were also measured with
      hand tally which served as the criterion. RESULTS: Absolute percent error was
      considerable and differed statistically between devices (P = 0.001); however,
      error improved for accelerometers when LFE was applied (Hip-DF: 31.6 +/- 18.8%;
      Hip-LFE: 9.7 +/- 12.8%; Wrist-DF: 32.7 +/- 14.2%; Wrist-LFE: 13.6 +/- 10.2%;
      Pedometer: 23.2 +/- 22.8%). Bland-Altman plots indicated underestimation of steps
      for accelerometers and the pedometer. Application of LFE, however, improved the
      prediction of the accelerometers. The number of steps measured by the hip
      accelerometer with LFE and by the pedometer did not differ statistically from
      actual steps. Steps by the remaining methods were significantly lower than hand
      tally (P <= 0.001). Correlations between percent error for each device and
      walking speed, anthropometry, age or sex ranged between -0.28 and +0.48, and were
      non-significant, except for age. CONCLUSIONS: The results demonstrated that the
      pedometer and ActiGraph accelerometers have considerable error in measuring steps
      of persons with DS. Application of LFE, however, significantly improved the step
      counting performance of the Actigraph accelerometers.

PMID- 30239067
TI  - Cascading effects from plants to soil microorganisms explain how plant species
      richness and simulated climate change affect soil multifunctionality.
AB  - Despite their importance, how plant communities and soil microorganisms interact
      to determine the capacity of ecosystems to provide multiple functions
      simultaneously (multifunctionality) under climate change is poorly known. We
      conducted a common garden experiment using grassland species to evaluate how
      plant functional structure and soil microbial (bacteria and protists) diversity
      and abundance regulate soil multifunctionality responses to joint changes in
      plant species richness (one, three and six species) and simulated climate change
      (3 degrees C warming and 35% rainfall reduction). The effects of species richness
      and climate on soil multifunctionality were indirectly driven via changes in
      plant functional structure and their relationships with the abundance and
      diversity of soil bacteria and protists. More specifically, warming selected for
      the larger and most productive plant species, increasing the average size within
      communities and leading to reductions in functional plant diversity. These
      changes increased the total abundance of bacteria that, in turn, increased that
      of protists, ultimately promoting soil multifunctionality. Our work suggests that
      cascading effects between plant functional traits and the abundance of
      multitrophic soil organisms largely regulate the response of soil
      multifunctionality to simulated climate change, and ultimately provides novel
      experimental insights into the mechanisms underlying the effects of biodiversity
      and climate change on ecosystem functioning.

PMID- 30239070
TI  - Paradoxical case effects of psoriasis following adalimumab therapy: A case
      series.

PMID- 30239069
TI  - The Emergency Medicine Specimen Bank: An Innovative Approach To Biobanking In
      Acute Care.
AB  - The Emergency Medicine Specimen Bank (EMSB) was developed to facilitate precision
      medicine in acute care. The EMSB is a biorepository of clinical health data and
      biospecimens collected from all adult English- or Spanish-speaking individuals
      who are able and willing to provide consent and are treated at the UCHealth
      University of Colorado Hospital Emergency Department. The EMSB is the first acute
      care biobank that seeks to enroll all patients, with all conditions who present
      to the ED. Acute care biobanking presents many challenges that are unique to
      acute care settings such as providing informed consent in a uniquely stressful
      and fast-paced environment and collecting, processing, and storing samples for
      tens of thousands of patients per year. Here, we describe the process by which
      the EMSB overcame these challenges and was integrated into clinical workflow
      allowing for operation 24 hours a day, 7 days a week at a reasonable cost. Other
      institutions can implement this template, further increasing the power of
      biobanking research to inform treatment strategies and interventions for common
      and uncommon phenotypes in acute care settings.

PMID- 30239071
TI  - Multiple Bowen's diseases and basal cell carcinomas in a patient with acute
      promyelocytic leukemia treated with arsenic trioxide: A case report and effective
      treatment with photodynamic therapy.
AB  - It is very rare that multiple Bowen's disease (BD) and basal cell carcinoma (BCC)
      lesions develop in a single patient. Routine therapy for the multiple lesions is
      not satisfactory. The present authors report on a patient who had developed
      multiple BD and BCC lesions for 12 years after arsenic trioxide treatment for his
      acute promyelocytic leukemia 20 years before. The patient with multiple lesions
      was successfully treated with photodynamic therapy.

PMID- 30239072
TI  - Assessment of discharge treatment prescribed to women admitted to hospital for
      hyperemesis gravidarum.
AB  - AIMS: Prescribing drug treatment for the management of hyperemesis gravidarum
      (HG), the most severe form of nausea and vomiting in pregnancy, remains
      controversial. Since most manufacturers do not recommend prescribing antiemetics
      during pregnancy, little is known regarding which treatments are most prevalent
      among pregnant patients. Here, we report for the first time, evidence of actual
      treatments prescribed in English hospitals. METHODS: A retrospective pregnancy
      cohort was constructed using anonymised electronic records in the Nottingham
      University Hospitals Trust system for all women who delivered between January
      2010 and February 2015. For women admitted to hospital for HG, medications
      prescribed on discharge were described and variation by maternal characteristics
      was assessed. Compliance with local and national HG treatment guidelines was
      evaluated. RESULTS: Of 33 567 pregnancies (among 30 439 women), the prevalence of
      HG was 1.7%. Among 530 HG admissions with records of discharge drugs, cyclizine
      was the most frequently prescribed (almost 73% of admissions). Prochlorperazine
      and metoclopramide were prescribed mainly in combination with other drugs;
      however, ondansetron was more common than metoclopramide at discharge from first
      and subsequent admissions. Steroids were only prescribed following readmissions.
      Thiamine was most frequently prescribed following readmission while high dose of
      folic acid was prescribed equally after first or subsequent admissions.
      Prescribing showed little variation by maternal age, ethnicity, weight,
      socioeconomic deprivation, or comorbidities. CONCLUSION: Evidence that management
      of HG in terms of discharge medications mainly followed local and national
      recommendations provides reassurance within the health professional community.
      Wider documentation of drugs prescribed to women with HG is required to enable
      full assessment of whether optimal drug management is being achieved.

PMID- 30239073
TI  - Establishing US norms for the Adult ADHD Self-Report Scale (ASRS-v1.1) and
      characterising symptom burden among adults with self-reported ADHD.
AB  - AIMS: To estimate Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist
      normative total scores among the US adult general population and to evaluate
      overall attention-deficit hyperactivity disorder (ADHD) symptom burden among US
      adults with ADHD. METHODS: Prior 2012 and 2013 US National Health and Wellness
      Survey respondents were re-contacted. Demographics, comorbidities, and ASRS-v1.1
      data were collected. ASRS-v1.1 scores were compared by sex, age, ADHD diagnosis,
      and ADHD medication use. Group differences were evaluated using chi-square tests
      and independent samples t-tests for categorical and continuous variables,
      respectively. RESULTS: Of 22 397 respondents, 465 self-reported being diagnosed
      with ADHD by a physician; of these, 174 self-reported using ADHD medication. The
      mean ASRS-v1.1 total score was 2.0 (SD = 3.2); scores differed by age and sex
      (all, P < 0.001). ADHD (vs no ADHD) was associated with depression (58.1% vs
      18.0%), anxiety (53.1% vs 16.0%), and sleep difficulties (37.0% vs 14.0%) (all, P
      < 0.001). ADHD medication use (vs no use) was associated with depression (68.4%
      vs 51.9%), anxiety (67.2% vs 44.7%), panic disorder (25.9% vs 17.2%), and
      insomnia (27.6% vs 19.6%) (all, P < 0.05). ADHD (vs no ADHD) respondents scored
      higher on all 18 ASRS-v1.1 items (all, P < 0.05). Medication users (vs non-users)
      scored higher on six items (all, P < 0.05). DISCUSSION: Adult ADHD may be
      undertreated or sub-optimally treated, despite a high symptom burden. Normative
      data will allow comparisons with individuals' scores to support the assessment of
      ADHD symptom burden among adults. CONCLUSION: Findings highlight the importance
      of assessing ADHD symptom burden, especially among adults presenting with
      comorbidities.

PMID- 30239074
TI  - Synergistic effects of marijuana abuse and HIV infection on neural activation
      during a cognitive interference task.
AB  - Marijuana use, which is disproportionately prevalent among human immunodeficiency
      virus (HIV)-infected persons, can alter activity in fronto-parietal regions
      during cognitively demanding tasks. While HIV is also associated with altered
      neural activation, it is not known how marijuana may further affect brain
      function in this population. Our study examined the independent and additive
      effects of HIV infection and regular marijuana use on neural activation during a
      cognitive interference task. The sample included 93 adults who differed on
      marijuana (MJ) and HIV statuses (20 MJ+/HIV+, 19 MJ+/HIV-, 29 MJ-/HIV+, 25 MJ
      /HIV-). Participants completed a counting Stroop task during a functional
      magnetic resonance imaging scan. Main and interactive effects on neural
      activation during interference versus neutral blocks were examined using a mixed
      effects analysis. The sample showed the expected Stroop effect for both speed and
      accuracy. There were main effects of MJ in the right and left inferior parietal
      lobules, with the left cluster extending into the posterior middle temporal gyrus
      and a main effect of HIV in the dorsal anterior cingulate cortex. There was an
      interaction in the left fronto-insular cortex, such that the MJ+/HIV+ group had
      the largest increase in activation compared with other groups. Among MJ+, signal
      change in this cluster correlated positively with cumulative years of regular
      marijuana use. These results suggest that comorbid HIV and marijuana use is
      associated with complex neural alterations in multiple brain regions during
      cognitive interference. Follow-up research is needed to determine how marijuana
      related characteristics may moderate HIV neurologic disease and impact real-world
      functioning.

PMID- 30239075
TI  - Evaluating cognitive screening instruments with the "likelihood to be diagnosed
      or misdiagnosed" measure.
AB  - OBJECTIVES: To calculate "number needed to diagnose" (NND), "number needed to
      predict" (NNP), and "number needed to misdiagnose" (NNM) for cognitive screening
      instruments which are commonly used in suspected dementia and mild cognitive
      impairment, and from these to calculate a "likelihood to be diagnosed or
      misdiagnosed" (LDM) metric as the ratio of NNM to either NND or NNP. METHODS:
      Datasets from pragmatic diagnostic test accuracy studies examining four commonly
      used cognitive screening instruments (Mini-Mental State Examination, MMSE;
      Montreal Cognitive Assessment, MoCA; Mini-Addenbrooke's Cognitive Examination,
      MACE; Six-item Cognitive Impairment Test, 6CIT) were analysed to calculate NND,
      NNP, and NNM, and from these derive values for LDM. FINDINGS: Although all the
      tests had low NND and NNP as desired, NNM was also low. Hence, only MMSE and 6CIT
      achieved LDM > 1 for dementia diagnosis, and only MACE and 6CIT had LDM > 1 for
      diagnosis of mild cognitive impairment. CONCLUSIONS: The likelihood to be
      diagnosed or misdiagnosed (LDM) metric may indicate the utility or inutility of
      diagnostic tests for clinicians and patients. LDM values may clarify the
      inevitable trade-off between sensitivity and specificity and hence clinician
      purpose in administering the diagnostic test (minimising false negatives or false
      positives).

PMID- 30239076
TI  - Observation of Carbodicarbene Ligand Redox Noninnocence in Highly Oxidized Iron
      Complexes.
AB  - To probe the possibility that carbodicarbenes (CDCs) are redox active ligands,
      all four members of the redox series [Fe(1)2 ]n+ (n=2-5) were synthesized, where
      1 is a neutral tridentate CDC. Through a combination of spectroscopy and DFT
      calculations, the electronic structure of the pentacation is shown to be [FeIII
      (1.+ )2 ]5+ (S= 1/2 ). That of [Fe(1)2 ]4+ is more ambiguous, but it has
      significant contributions from the open-shell singlet [FeIII (1)(1.+ )]4+ (S=0).
      The observed spin states derive from antiferromagnetic coupling of their
      constituent low-spin iron(III) centres and cation radical ligands. This marks the
      first time redox activity has been observed for carbones and expands the diverse
      chemical behaviour known for these ligands.

PMID- 30239077
TI  - Intranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative
      stress and markedly inhibits ethanol consumption and post-deprivation relapse
      drinking.
AB  - Chronic ethanol consumption leads to brain oxidative stress and
      neuroinflammation, conditions known to potentiate and perpetuate each other.
      Several studies have shown that neuroinflammation results in increases in chronic
      ethanol consumption. Recent reports showed that the intra-cerebroventricular
      administration of mesenchymal stem cells to rats consuming alcohol chronically
      markedly inhibited oxidative-stress, abolished neuroinflammation and greatly
      reduced chronic alcohol intake and post deprivation relapse-like alcohol intake.
      However, the intra-cerebroventricular administration of living cells is not
      suitable as a treatment of a chronic condition. The present study aimed at
      inhibiting ethanol intake by the non-invasive intranasal administration of human
      mesenchymal stem cell products: exosomes, microvesicles (40 to 150 nm) with
      marked antioxidant activity extruded from mesenchymal stem cells. The exosome
      membrane can fuse with the plasma membrane of cells in different tissues, thus
      delivering their content intracellularly. The study showed that the weekly
      intranasal administration of mesenchymal stem cell-derived exosomes to rats
      consuming alcohol chronically (1) inhibited their ethanol intake by 84 percent
      and blunted the relapse-like 'binge' drinking that follows an alcohol deprivation
      period and ethanol re-access. (2) Intranasally administered exosomes were found
      in the brain within 24 hours; (3) fully reversed both alcohol-induced hippocampal
      oxidative-stress, evidenced by a lower ratio of oxidized to reduced glutathione,
      and neuroinflammation, shown by a reduced astrocyte activation and microglial
      density; and (4) increased glutamate transporter GLT1 expression in nucleus
      accumbens, counteracting the inhibition of glutamate transporter activity,
      reportedly depressed under oxidative-stress conditions. Possible translational
      implications are envisaged.

PMID- 30239078
TI  - Stable Face-to-Face Singlet Diradicaloids: Triply Linked Corrole Dimer
      Gallium(III) Complexes with Two MU-Hydroxo-Bridges.
AB  - In known singlet diradicaloid molecules, two inherent radicals are interacted
      antiferromagnetically as a result of delicate energetic balances between closed
      shell and open-shell states. Reported herein is that gallium(III) metalations of
      triply linked corrole dimers provide face-to-face dimers, with two MU-hydroxo
      bridges, and they display curved pi-planes nearing each other at about 3.24 A.
      Based on ESR and SQUID measurements, and theoretical calculations, the dimers
      have been assigned as singlet diradicaloids that consist of two monoradicals each
      delocalized on the triply linked corrole dimer planes. Therefore, it is concluded
      that the dimers have unusual open-shell states stabilized by large through-space
      spin-exchange interactions.

PMID- 30239079
TI  - Cyclodextrin-Based [3]Rotaxane-Crosslinked Fluorescent Polymer: Synthesis and De
      Crosslinking Using Size Complementarity.
AB  - Vinyl-group-substituted, alpha-cyclodextrin-based, size-complementary
      [3]rotaxanes were synthesized as crosslinkers for rotaxane-crosslinked
      poly(methyl methacrylate) (RCP) by radical polymerization. The size
      complementarity of the crosslinkers made it possible to de-crosslink the RCP by
      heating, and the degree of decoupling was monitored by fluorescence intensity,
      depending on the state of the axle component of the rotaxane crosslink moiety.

PMID- 30239080
TI  - A Charge-Separated State that Lives for Almost a Second at a Conductive Metal
      Oxide Interface.
AB  - Transparent conductive oxides (TCOs) are widely used commercially available
      materials for opto-electronic applications, yet they have received very little
      attention for dye-sensitization applications. Now, mesoporous thin films of
      conductive indium-doped tin oxide (ITO) nanocrystallites are shown to support
      long-lived charge separation with first-order recombination kinetics (k=1.5 s-1
      ). A layer-by-layer technique was utilized to spatially arrange redox and/or
      chromophoric molecular components on ITO. Spectroelectrochemical measurements
      demonstrated that upon light absorption, each component provided a free-energy
      gradient to direct electron transfer at the conductive oxide interface. The long
      lived nature of the photogenerated charge separated states provide favorable
      conditions for photocatalytic solar fuel production. Furthermore, the first-order
      recombination kinetics are most ideal for the fundamental understanding of
      interfacial charge separation dynamics.

PMID- 30239081
TI  - Biomimetic Synthesis of (+)-Aspergillin PZ.
AB  - The cytochalasans are a large family of polyketide natural products with potent
      bioactivities. Amongst them, the aspochalasins show particularly intricate and
      fascinating structures. To gain insight into their structural diversity and
      innate reactivity, we have developed a rapid synthesis of aspochalasin D, the
      central member of the family. It proceeded in 13 steps starting from divinyl
      carbinol and utilized a high pressure Diels-Alder reaction that features high
      regio- and stereoselectivity. So far, our work has culminated in a biomimetic
      synthesis of aspergillin PZ, an intricate pentacyclic aspochalasan.

PMID- 30239082
TI  - Mechanically Responsive Crystalline Coordination Polymers with Controllable
      Elasticity.
AB  - Crystalline coordination polymers tend to be brittle and inelastic, however, we
      now describe a family of such compounds that are capable of displaying mechanical
      elasticity in response to external pressure. The design approach successfully
      targets structural features that are critical for producing the desired
      mechanical output. The elastic crystals all comprise 1D cadmium(II) halide
      polymeric chains with adjacent metal centres bridged by two halide ions resulting
      in the required stacking interactions and short "4 A" crystallographic axes.
      These polymeric chains (structural "spines") are further organized via hydrogen
      bonds and halogen bonds perpendicular to the direction of the chains. By
      carefully altering the strength and the geometry of these non-covalent
      interactions, we have demonstrated that it is possible to control the extent of
      elastic bending in crystalline coordination compounds.

PMID- 30239083
TI  - Changes in resuscitation and end-of-life documentation in older patients'
      clinical case notes: A comparison of 2011 and 2017 practice.
AB  - OBJECTIVE: To compare 2011 and 2017 documentation of resuscitation decisions in
      older patients, including the frequency and clarity of documentation. METHODS:
      The clinical case notes of 130 patients aged 70 years and over were examined to
      identify how resuscitation decisions are discussed and documented at a major
      teaching hospital. Results were compared to 2011 data. RESULTS: The proportion of
      patients with a documented order significantly increased, from 34 to 63%, with a
      concurrent increased number of patients identified as Not For Cardiopulmonary
      Resuscitation (Not for CPR). The standardised documentation has also improved
      rates of documented discussion, legibility and identification of the involved
      doctor. CONCLUSION: The Resuscitation Plan 7-Step Pathway has markedly improved
      the frequency of documented discussion, the rate of recorded Not For CPR status
      and clarity of documentation. There is scope for improvement as this policy is
      embraced across South Australia.

PMID- 30239084
TI  - Aerobic Solid State Red Phosphorescence from Benzobismole Monomers and
      Patternable Self-Assembled Block Copolymers.
AB  - The synthesis of the first bismuth-containing macromolecules that exhibit
      phosphorescence in the solid state and in the presence of oxygen is reported.
      These red emissive high molecular weight polymers (>300 kDa) feature
      benzobismoles appended to a hydrocarbon scaffold, and were built via an efficient
      ring-opening metathesis (ROMP) protocol. Moreover, our general procedure readily
      allows for the formation of cross-linked networks and block copolymers. Attaining
      stable red phosphorescence with non-toxic elements remains a challenge and, thus,
      our new class of soluble (processable) polymeric phosphor is of great interest.
      Furthermore, the formation of bismuth-rich cores within organic-inorganic block
      copolymer spherical micelles is possible, leading to patterned arrays of bismuth
      in the film state.

PMID- 30239086
TI  - How to repair parastomal hernias involving the abdominal apron: to move or not to
      move.

PMID- 30239085
TI  - Minimizing Propionibacterium acnes contamination in shoulder arthroplasty: use of
      a wound protector.
AB  - BACKGROUND: Propionibacterium acnes may be transmitted from the subdermal tissues
      to the deeper tissues during shoulder arthroplasty surgery, resulting in deep
      infection. The aim of this prospective, clinical study was to determine whether
      the use of a wound protector drape can lower the incidence of P. acnes in the
      wound during shoulder arthroplasty surgery. METHODS: For a consecutive series of
      47 patients undergoing shoulder arthroplasty, a wound protector drape was used
      during surgery, to isolate the subdermal layer from the surgeons' hands,
      retractors and other instruments. Microbiological swabs were taken both from the
      subdermal layer and the exposed drape to determine the incidence of P. acnes at
      both sites. RESULTS: The overall incidence of P. acnes in the subdermal layer was
      23%. A fivefold decrease in the incidence of P. acnes in the exposed superficial
      layer was demonstrated by use of the wound protector drape. CONCLUSION: Use of a
      wound protector drape to isolate the superficial tissue layer from the surgeons'
      gloves, instruments and retractors decreases the incidence of P. acnes in the
      surgical field. This may result in a decreased rate of transmission to the deeper
      tissues, and a decreased rate of P. acnes deep infection.

PMID- 30239087
TI  - Chest pain that does not make the cut: a case study of a surgical patient with
      Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis syndrome.

PMID- 30239088
TI  - Risk factors for infection in patients with chronic leg ulcers: A survival
      analysis.
AB  - AIM: This study aimed to validate the relationships between possible predictive
      factors and clinically diagnosed infection in adult patients with chronic leg
      ulcers. METHODS: This study used a sample of 636 adult participants whose ulcers
      were diagnosed as either venous, arterial or mixed aetiology leg ulcers and had
      no clinical signs of infection at recruitment. Data were extracted from
      recruitment to 12 weeks from six longitudinal prospective studies from 2004 to
      2015. Survival analysis was used to investigate mean time-to-infection, including
      the Kaplan-Meier method and the Cox proportional-hazards regression model.
      RESULTS: The sample included 74.7% venous, 19.6% mixed and 5.7% arterial leg
      ulcers. There were 101 (15.9%) participants diagnosed with infection at least
      once within 12 weeks of follow-up. Mean time-to-infection was 10.89 weeks (95% CI
      = 10.66-11.12). After adjustment for potential confounders, a Cox proportional
      hazards regression model found that depression, using walking aids, calf ankle
      ratio <1.3, wound area >=10 cm2 and ulcers with slough tissue at recruitment were
      significant risk factors for wound infection. CONCLUSION: This study has
      validated the predictive ability of factors which have been found in a cross
      sectional study to be significantly associated with infection in patients with
      leg ulcers, including venous leg ulcers, arterial leg ulcers and mixed aetiology
      leg ulcers. Results showed that patients with chronic leg ulcers, who either
      presented with depression, used walking aids, had a calf ankle ratio <1.3, a
      wound area >=10 cm2 or an ulcer with slough tissue, had greater likelihood of
      developing infection compared to those without these factors.

PMID- 30239089
TI  - Pharmacological and non-surgical renal protective strategies for cardiac surgery
      patients undergoing cardiopulmonary bypass: a systematic review.
AB  - BACKGROUND: Post-operative acute kidney injury after cardiopulmonary bypass (AKI
      CPB) for cardiac surgery is a frequent complication. It may require renal
      replacement therapy (RRT), which is associated with an increased morbidity and
      mortality. This review explores the efficacy of proposed pharmacological and non
      surgical renal protective strategies. METHODS: A comprehensive literature search
      was done using Ovid MEDLINE, Embase and Scopus databases. Keywords included were
      cardiopulmonary bypass, cardiac surgery, coronary artery bypass, renal protection
      and renal preservation. Eligible articles consisted of all studies on patients
      who had undergone cardiac surgery via CPB with an outcome of AKI and/or RRT
      reported. All studies underwent a quality check via the risk of bias tool. The
      three most researched interventions (based on number of randomized controlled
      trials and total patients analysed) and their renal outcomes were then analysed
      with Review Manager Software. RESULTS: Eighty-eight articles were extracted. A
      total of 26 management strategies for renal protection following CPB were
      identified. N-acetylcysteine (NAC), remote ischaemic preconditioning (RIPC) and
      the use of volatile anaesthetic agents (VAAs) were further analysed. NAC, RIPC
      and VAA had no statistically significant benefit in reducing either AKI-CPB or
      the need for RRT following CPB. CONCLUSION: NAC, RIPC and VAA were found to have
      no statistical significant benefit in reducing either AKI-CPB or the need for RRT
      following CPB. There remains clinical uncertainty with all currently proposed
      pharmacological and non-surgical renal protective strategies for CPB. Future
      research in this area should analyse the effects of combined interventions or
      specifically focus on 'at-risk' patients.

PMID- 30239090
TI  - Prevalence and nature of lung function abnormalities among indigenous Australians
      referred to specialist respiratory outreach clinics in the Northern Territory.
AB  - BACKGROUND AND OBJECTIVE: Poor lung function is a predictor of future all-cause
      mortality. In Australia, respiratory diseases are particularly prevalent among
      the Indigenous population, especially in remote communities. However, there are
      little published pulmonary function tests (PFT) data of remote-based adult
      Indigenous patients. We aimed to evaluate the severity of airflow obstruction and
      other PFT abnormalities of adults referred to specialist respiratory clinics in
      remote Indigenous communities. METHODS: Retrospective analysis of PFTs [pre- and
      post-bronchodilator spirometry, total lung capacity (TLC) and diffusing capacity
      to carbon monoxide (DLCO)] of Indigenous patients collected during specialist
      respiratory clinics in remote Northern Territory (NT) Indigenous communities
      (Australia) between 2013-2015. The National Health and Nutrition Examination
      Survey (NHANES) III without ethnic correction was used as the reference. RESULTS:
      Of the 357 patients, 150 had acceptable spirometry and 71 had acceptable DLCO and
      TLC studies. Despite the relatively young age (mean=49 years, SD=12.9) their lung
      function was generally low; mean % predicted values were FEV1 =55%(SD=20.5%),
      FVC=61%(SD=15.6%), DLCO=64.0%(SD=19.7%), TLC=70.1%(SD=18.2%). Mean FEV1 /FVC
      ratio was preserved (0.71, SD=0.16). Post-bronchodilator airflow obstruction
      (FEV1 /FVC<0.7) was found in 37% of patients, where a large proportion (67%)
      demonstrated at least severe airflow obstruction with a mean FEV1 of 41%
      predicted. CONCLUSION: In this first study of PFT findings of Indigenous adults
      from a remote-based clinical service, we found a high rate of at least moderate
      airflow limitation and low FVC along with preserved FEV1/FVC ratio. Increased
      awareness and screening for reduced lung function needs to be considered in this
      population. This article is protected by copyright. All rights reserved.

PMID- 30239091
TI  - Magneto-Controlled Biocatalytic Cascades with Logically Processed Input Signals -
      Substrate Channeling versus Free Diffusion.
AB  - Magnetic nanoparticles (MNPs) functionalized with various enzymes
      (amyloglucosidase, glucose oxidase and horseradish peroxidase) were used to
      perform biocatalytic cascades in two different states, solute suspension or
      aggregated, produced in the absence or presence of an external magnetic field.
      The biocatalytic reactions proceeded through bulk solution diffusion of
      intermediate substrates or substrate channeling, when the systems were dispersed
      or aggregated, respectively. The both pathways have shown very similar kinetics,
      unless the intermediate substrate was consumed by an additional biocatalytic
      process called "filter" for brevity. In the presence of the "filter" process, the
      diffusional process in the bulk solution was significantly inhibited, while the
      process based on the substrate channeling was still active. The systems were
      switched reversibly between the inhibited dispersed state and the active
      aggregated state by removing and applying the external magnetic field,
      respectively. The signal-controlled biocatalytic cascades were considered as
      Boolean logic circuits with the inputs consisting of biomolecules and the
      magnetic field on-off.

PMID- 30239092
TI  - Impact of Alkali-Metal Impregnation on MIL-101 (Cr) Metal-Organic Frameworks for
      CH4 and CO2 Adsorption Studies.
AB  - In this article, an assessment of the impact of alkali-metal-ion impregnation on
      metal-organic frameworks (MOF) is presented employing CH4 and CO2 adsorption
      isotherm data. At first, the parent MOF, MIL-101(Cr), is prepared by a fluorine
      free hydrothermal reaction procedure and impregnated with Li, Na, and K alkali
      cations. These synthesised MOFs are characterized by N2 adsorption/desorption
      isotherm analysis, X-ray diffraction (XRD) measurement and scanning electron
      microscopy (SEM). The amount of CH4 and CO2 adsorption uptakes onto parent and
      alkali ions impregnated MIL-101(Cr) are conducted for wide ranges of pressures
      and temperatures. For understanding the effects of MOF synthesis process and
      alkali cations impregnation, CH4 /CO2 uptakes on perfect crystalline MIL-101(Cr)
      MOF are also calculated by Grand Canonical Monte Carlo (GCMC) simulation and the
      results are compared with experimental isotherm data of synthesised parent and
      alkali ions impregnated MIL-101(Cr) MOFs. It is found that the limiting uptakes
      and the isosteric heats are mainly influenced by the modified adsorbent
      structures due to alkali ions impregnation and the polarity of adsorbate
      molecules. Employing Dubinin-Astakhov (DA) equation, the energy distribution of
      synthesised parent and alkali doped MIL-101 (Cr) MOFs are also presented to
      identify the alkali cation effects and the surface heterogeneity.

PMID- 30239093
TI  - Intra-abdominal desmoid tumour presenting as an acute abdomen.

PMID- 30239094
TI  - High Resolution for Chemical Shifts and Scalar Coupling Constants: The 2D Real
      Time J-Upscaled PSYCHE-DIAG.
AB  - The facile determination of chemical shift and scalar coupling constants in NMR
      spectra is often prevented by spectral overlap and limited resolution. Here, we
      present a high-resolution NMR experiment for the simultaneous detection of both
      resonance frequencies and coupling patterns even with small J-values. A PSYCHE
      decoupled DIAG (Pure Shift Yielded by Chirp Excitation- DIAGonal) experiment,
      which resolves chemical shift in the indirect dimension of a 2D experiment is
      combined with real-time J-upscaling in order to visualize small coupling
      constants that would otherwise be hidden in the linewidth of a regular proton or
      DIAG spectrum.

PMID- 30239095
TI  - Dramatic progression of a chest wall desmoid-like fibromatosis.

PMID- 30239096
TI  - Karydakis procedure can be effectively performed in the lateral position.
AB  - BACKGROUND: Karydakis published a large pilonidal series in 1992, reporting a
      recurrence rate of less than 1% and complication rate of 8.5%. The aim of this
      study was to compare the outcomes of Karydakis procedure (KP) performed in the
      lateral versus the prone position in a consecutive series. METHODS: Ninety-seven
      consecutive patients undergoing a KP between March 2000 and February 2018 were
      retrospectively assessed. Patients with disease sinuses or fistulas extending
      from the midline to either left or right sides only were considered for KP in the
      contralateral side position. RESULTS: Surgery was carried out for primary
      pilonidal disease in 71 patients (73%) and for recurrent disease in 26 patients
      (27%). The majority (62%) of pilonidal tracts veered off from the midline to
      either the left or right side only. Wound complications, mostly minor skin
      separation, occurred in 37 patients (38%). Disease recurrence occurred in eight
      patients (8%). There was no difference between patients who had KP in a lateral
      position compared with those operated in a prone position regarding wound
      complications (41% versus 35%, P = 0.675), disease recurrence (9% versus 7%, P =
      1.000), mean operating time (64.6 min versus 66.6 min, P = 0.259) and mean length
      of hospital stay (1 day for both groups). CONCLUSIONS: Pilonidal surgery in the
      lateral position has potential benefits for patient safety, patient comfort and
      theatre efficiency. The clinical results of this series show that the KP can be
      performed safely and effectively with the patient in the lateral position for
      most cases of pilonidal disease.

PMID- 30239097
TI  - Mycobacterium ulcerans disease management in Australian patients: the re
      emergence of surgery as an important treatment modality.
AB  - With the demonstration of the effectiveness of antibiotic treatment, the
      management of Mycobacterium ulcerans disease has changed from a predominantly
      surgically to a predominantly medically treated disease. However, research among
      Australian patients has revealed that antibiotic treatment alone is associated
      with prolonged wound healing times, high rates of treatment toxicity, and the
      potential for significant tissue destruction associated with severe paradoxical
      reactions. We present the current state of M. ulcerans management in Barwon
      Health, Australia, where a close working relationship exists between the Plastic
      Surgical and Infectious Diseases units. Here treatment has evolved based on
      nearly 20 years of experience gained from managing more around 600 patients from
      a M. ulcerans epidemic on the nearby Bellarine and Mornington Peninsulas. In our
      experience, surgery has re-emerged to play an important role in the treatment of
      M. ulcerans in improving the rate of wound healing, minimizing antibiotic
      associated toxicity and preventing further tissue loss associated with severe
      paradoxical reactions. For selected small lesions surgery without antibiotics may
      also be an effective treatment option, however aggressive surgical resection of
      lesions with wide margins through uninvolved tissue should no longer be
      performed. Furthermore, extensive excisional surgery that will require the use of
      split skin grafts and vascularized tissue flaps to repair skin defects should be
      avoided if possible.

PMID- 30239098
TI  - Experience coercion, post-traumatic stress, and satisfaction with treatment
      associated with different coercive measures during psychiatric hospitalization.
AB  - Coercive measures are frequently used in psychiatric hospitalization. However,
      there are few studies that analyse perceived coercion, post-traumatic stress, and
      subjective satisfaction with the hospitalization treatment associated with
      different types of coercive measures. The sample consisted of 111 patients
      admitted to two psychiatric units and divided into three groups based on the
      measure applied: involuntary medication (N = 41), mechanical restraint (N = 32),
      and combined measures (mechanical restraint and involuntary medication; N = 38).
      The outcome variables were perceived coercion evaluated with the Coercion
      Experience Scale (CES), post-traumatic stress evaluated with the Davidson Trauma
      Scale (DTS), and satisfaction with the treatment evaluated with the Client's
      Assessment of Treatment (CAT). The results found higher levels of perceived
      coercion associated with the use of mechanical restraint (P = 0.002) and combined
      measures (P < 0.001) in comparison with involuntary medication. Additionally, in
      relation to post-traumatic stress, mechanical restraint (P = 0.013) and combined
      measures (P = 0.004) were more stressful compared to involuntary medication.
      Finally, the use of combined measures was associated with lower satisfaction with
      inpatient psychiatric treatment compared to the use of involuntary medication (P
      = 0.006). The following recommendation would be consistent with the results
      found: if a patient does not specify a preference for some type of measure,
      involuntary medication could be used and mechanical restraint avoided, especially
      when used in combination with involuntary medication.

PMID- 30239099
TI  - Clinical evaluation of anal intraepithelial neoplasia: are we missing the boat?
AB  - BACKGROUND: Anal intraepithelial neoplasia (AIN) is dysplasia in the epithelium
      of the anus and is a pre-malignant condition associated with a low rate of
      progression to invasive squamous cell carcinoma (SCC). The natural history of
      progression for AIN to anal SCC is poorly defined. This study aims to review our
      experience with AIN and investigate the natural history of progression. METHODS:
      Data on all patients with AIN from January 2005 to December 2015 were
      retrospectively reviewed. Three separate databases were searched - Colorectal,
      Radiation Oncology and Infectious Diseases. All databases were cross-referred to
      obtain a complete but non-duplicated data set. Electronic charts were reviewed to
      obtain clinical information. RESULTS: Twenty-eight patients were identified with
      AIN of various grades. There were 25 males, three females. Twenty of the male
      patients were human immunodeficiency virus (HIV) positive. Mean length of follow
      up was 56 months. Complete regression of AIN to normal was noted in 13 patients
      (46%). Four patients had persisting AIN III with no evidence of regression or
      malignant transformation. Nine patients with pre-existing AIN developed SCC
      (32%). Seven were positive for HIV infection (all males). Median time to
      progression was 36 months. None of the patients demonstrated clear linear pattern
      of progression of AIN to SCC. CONCLUSION: High grade AIN may progress to anal SCC
      and surveillance is indicated. The exact natural history of progression for AIN
      is difficult to predict. There is no linear progression over time evident. HIV
      patients with AIN are at higher risk of developing SCC.

PMID- 30239100
TI  - Primary anterior abdominal wall leiomyoma in a pregnant woman.

PMID- 30239101
TI  - Day case versus inpatient stay for excisional haemorrhoidectomy.
AB  - BACKGROUND: Excisional haemorrhoidectomy has traditionally been performed on an
      inpatient basis due to concerns over post-operative pain and urinary retention.
      Day case procedures are increasingly common. This study aims to investigate
      readmission rates following day case compared with inpatient haemorrhoidectomy.
      METHODS: A retrospective cohort review of all haemorrhoidectomies performed at
      Counties Manukau District Health Board, Auckland from January 2012 to December
      2017 was queried from the hospital database. Readmission rates, reason for
      readmission, time to represent and length of stay within 30 days were recorded.
      Continuous data were analysed using Mann-Whitney U and Student's t-tests.
      Categorical data were analysed using the Fisher's exact and chi-squared tests.
      RESULTS: A total of 485 cases of excisional haemorrhoidectomy were performed,
      with 62 (12.8%) readmissions within 30 days. There were 170 patients who were
      treated as day cases with 19 (11.2%) readmissions; 315 patients stayed one night
      or longer with 43 (13.7%) readmissions (P = 0.97). The demographics of both
      groups were similar. Pain and bleeding were the most common reasons for
      readmission in both groups. There were no significant differences between rates
      of readmission, length of stay following readmission and time to readmission
      between day case and inpatient groups. CONCLUSIONS: Day case surgery should be
      considered as an alternative to inpatient surgery for excisional
      haemorrhoidectomy and can be achieved without increase in hospital readmissions.

PMID- 30239102
TI  - Single-Step Per-O-Sulfonation of Sugar Oligomers with Concomitant 1,6-Anhydro
      Bridge Formation for Binding Fibroblast Growth Factors.
AB  - Many circulating cancer-related proteins, such as fibroblast growth factors
      (FGFs), associate with glycosaminoglycans-particularly heparan sulfate-at the
      cell surface. Disaccharide analogues of heparan sulfate had previously been
      identified as the shortest components out of the sugars that bind to FGF-1 and
      FGF-2. Taking note of the typical pose of l-iduronic acid, we conceived of per-O
      sulfonated analogues of such disaccharides, and devised a single-step procedure
      for per-O-sulfonation of unprotected sugars with concomitant 1,6-anhydro bridge
      formation to achieve such compounds through direct use of SO3 ?Et3 N as
      sulfonation reagent and dimethylformamide as solvent. The synthesized sugars
      based on the oligomaltose backbone bound FGF-1 and FGF-2 mostly at the sub
      micromolar level, although the tetrasaccharide analogue achieved low-nanomolar
      binding with FGF-2.

PMID- 30239103
TI  - Cystic lesion in the left upper quadrant.

PMID- 30239104
TI  - Experimental evidence of the role of heterochrony in evolution of the
      Mesoamerican cichlids pigment patterns.
AB  - The Mesoamerican cichlids display a spectacular diversity of pigment patterns,
      which serve a variety of functions and serve as a strong selective trait for this
      lineage. The development and variation of coloration in the Mesoamerican cichlids
      have been detailed by several groups. In particular, Rican, Musilova, Muska, and
      Novak () and Rican, Pialek, Dragova, and Novak () determined homology of pattern
      and revealed four alternative types of coloration and their ontogeny. In this
      work, this group posed an "ontogenetic timing hypothesis" proposing heterochronic
      shifts underlying major transitions in the evolution of the Mesoamerican
      cichlids. Here, we experimentally test this hypothesis by experimentally altering
      timing of pigment pattern formation in the convict cichlid Amatitlania
      nigrofasciata, a member of the Mesoamerican cichlids, via manipulations of
      thyroid hormone (TH) function. The response of different pigment cell lineages to
      TH-perturbations revealed that the transition from larval to juvenile coloration
      in the convict cichlid is under the control of TH-signaling. Importantly,
      hormonally induced changes in the timing of pigment cell lineages' development
      resulted in shifts of coloration ontogeny type observed between lineages and led
      to the appearance of phenotypes mimicking those in phylogenetically close and
      distant species. Thus, our findings support the hypothesis that simple changes in
      ontogenetic timing underlies species specific patterns in pigmentation and
      provide new perspectives for studying the role of endocrine signaling in the
      evolution of cichlids.

PMID- 30239105
TI  - Inguinal node metastases in testicular cancer following previous childhood
      orchidopexy.

PMID- 30239106
TI  - Streptolysin-induced endoplasmic reticulum stress promotes group A Streptococcal
      host-associated biofilm formation and necrotising fasciitis.
AB  - Group A Streptococcus (GAS) is a human pathogen that causes infections ranging
      from mild to fulminant and life-threatening. Biofilms have been implicated in
      acute GAS soft-tissue infections such as necrotising fasciitis (NF). However,
      most in vitro models used to study GAS biofilms have been designed to mimic
      chronic infections and insufficiently recapitulate in vivo conditions along with
      the host-pathogen interactions that might influence biofilm formation. Here, we
      establish and characterise an in vitro model of GAS biofilm development on
      mammalian cells that simulates microcolony formation observed in a mouse model of
      human NF. We show that on mammalian cells, GAS forms dense aggregates that
      display hallmark biofilm characteristics including a 3D architecture and enhanced
      tolerance to antibiotics. In contrast to abiotic-grown biofilms, host-associated
      biofilms require the expression of secreted GAS streptolysins O and S (SLO, SLS)
      that induce endoplasmic reticulum (ER) stress in the host. In an in vivo mouse
      model, the streptolysin null mutant is attenuated in both microcolony formation
      and bacterial spread, but pretreatment of soft-tissue with an ER stressor
      restores the ability of the mutant to form wild-type-like microcolonies that
      disseminate throughout the soft tissue. Taken together, we have identified a new
      role of streptolysin-driven ER stress in GAS biofilm formation and NF disease
      progression.

PMID- 30239107
TI  - Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental
      delay, alopecia, and dysmorphic features.
AB  - The ornithine decarboxylase 1 (ODC1) gene plays an important role in
      physiological and cell developmental processes including embryogenesis,
      organogenesis, and neoplastic cell growth. Here, we report an 32-month-old
      Caucasian female with a heterozygous de novo nonsense mutation in the ODC1 gene
      that leads to a premature abrogation of 14-aa residues at the ODC protein c
      terminus. This is the first human case confirming similar symptoms observed in a
      transgenic ODC1 mouse model first described over 20 years ago. Phenotypic
      manifestations include macrosomia, macrocephaly, developmental delay, alopecia,
      spasticity, hypotonia, cutaneous vascular malformation, delayed visual
      maturation, and sensorineural hearing loss. We here describe for the first time a
      new pediatric disorder that is directly linked to a de novo pathogenic variant in
      the ODC1 gene. The ODC1 gene mutation (c.1342 A>T) was identified by whole-exome
      sequencing and confirmed by Sanger sequencing. Red blood cells obtained from our
      patient showed elevated ODC protein and polyamine levels compared to healthy
      controls. Our autosomal dominant patient who carries this gain-of-function ODC1
      mutation may benefit from treatment with alpha-difluoromethylornithine, a well
      tolerated, U.S. Food and Drug Administration (FDA). FDA-approved drug.

PMID- 30239108
TI  - Ultrafast Maximum-Quantum NMR Spectroscopy for the Analysis of Aromatic Mixtures.
AB  - Maximum-quantum (MaxQ) NMR experiments have been introduced to overcome issues
      related to peak overlap and high spectral density in the NMR spectra of aromatic
      mixtures. In MaxQ NMR, spin systems are separated on the basis of the highest
      quantum coherence that they can form. MaxQ experiments are however time consuming
      and methods have been introduced to accelerate them. In this article, we
      demonstrate the ultrafast, single-scan acquisition of MaxQ NMR spectra using
      spatial encoding of the multiple-quantum dimension. So far, the spatial encoding
      methodology has been applied only for the encoding of up to double-quantum
      coherences, and here we show that it can be extended to higher coherence orders,
      to yield a massive reduction of the acquisition time of multi-quantum spectra of
      aromatic mixtures, and also to monitor chemical reactions.

PMID- 30239109
TI  - Determinants of impaired renal and vascular function are associated with elevated
      levels of procoagulant factors in the general population: reply.

PMID- 30239110
TI  - Ovarian-type epithelial tumour of borderline malignancy: a rare testicular tumour
      in Australia.

PMID- 30239112
TI  - Authors' reply re: Inadequate safety reporting in pre-eclampsia trials: a
      systematic evaluation.

PMID- 30239111
TI  - Prevalence and reasons for smoking in adolescent Swiss childhood cancer
      survivors.
AB  - BACKGROUND: Smoking harms health, particularly that of childhood cancer
      survivors, who face risk of pulmonary and cardiovascular diseases because of
      chemotherapy and radiotherapy to the chest. This nationwide study assessed
      smoking habits and reasons for smoking in adolescent survivors and healthy peers.
      METHODS: As part of the Swiss Childhood Cancer Survivor Study, we sent a
      questionnaire to all Swiss resident survivors, who were aged 16-19 years. We
      compared smoking status and reasons for smoking between 511 survivors, 141 of
      their siblings, and 1,727 adolescents in a representative population-based study,
      the Tobacco Monitoring Switzerland (TMS). RESULTS: Current smoking was less
      prevalent in survivors (17%) and their siblings (17%) compared with TMS (32%).
      Survivors and TMS adolescents gave similar reasons for smoking. Stress control,
      smoking being a habit, and good taste were the reasons for smoking cited most
      often in both groups. Peer smoking was more important in survivors (49%) than in
      TMS (34%, P = 0.004). Most important reasons for not smoking in both groups were
      smoking being unhealthy and not wanting to be addicted. CONCLUSIONS: In
      Switzerland, survivors smoke as often as their siblings but less than the general
      population. Peer smoking was a more important reason for smoking in survivors
      than in the general population, suggesting that reducing smoking in peers could
      result in a reduction of smoking in survivors. Overall, reasons for smoking were
      very similar, thus interventions to reduce smoking in survivors could be the same
      as those used in the general population.

PMID- 30239114
TI  - Pericardial empyema after cardiac surgery: a diagnostic challenge.

PMID- 30239113
TI  - Regional anesthesia with epinephrine-containing lidocaine reduces pericatheter
      bleeding after tunneled hemodialysis catheter placement.
AB  - INTRODUCTION: Pericatheter bleeding (PB) following tunneled hemodialysis catheter
      (THC) placement is a common phenomenon. In addition to complicating securement of
      the THC, the PB may loosen the adhesive catheter dressing and delay wound
      healing. The primary aim of this study was to determine whether epinephrine
      containing local anesthetics rather than plain ones reduce superficial PB after
      THC placement. METHODS: The study was based on the retrospective analysis of the
      prospectively gathered data. Forty-six patients receiving local analgesia during
      THC placement were randomly assigned in a double-blind manner to two groups
      according to local anesthetic mixtures used (n =22 to prilocaine group [group 1];
      n =24 to epinephrine-containing lidocaine group [group 2]). Presence or absence
      of PB after the THC placement was evaluated. Differences between groups with and
      without controlling other variables were statistically analyzed. FINDINGS:
      Epinephrine-containing lidocaine (group 2) significantly reduced PB in comparison
      with prilocaine, P = 0.003. Use of epinephrine-containing lidocaine (group 2) was
      associated with a reduction in the likelihood of PB (Odds ratio = 0.017).
      Meanwhile, use of prilocaine (group 1) had 59.7 times higher odds in the
      likelihood of PB after THC placement. Lower rate of systolic blood pressure (SBP)
      in group 2 patients after 5 minutes of injections was also noted, P = 0.008.
      Epinephrine-containing lidocaine was well tolerated and caused no significant
      cardiovascular disturbance. DISCUSSION: Local infiltration of epinephrine
      containing lidocaine instead of plain local anesthetics during THC insertion may
      reduce superficial PB and improve patient comfort.

PMID- 30239115
TI  - Living the intensive order: Common sense and schizophrenia in Deleuze and
      Guattari.
AB  - In Anti-Oedipus, Deleuze and Guattari aim to describe schizophrenia in a positive
      manner. According to them, the schizophrenic lives on the intensive order. To
      fully comprehend what this means, it is key to address some of Deleuze's insights
      regarding the notion of intensity in relation to experience and cognition. This
      is why I will combine ideas from Anti-Oedipus with theory from Difference and
      Repetition, in order to explain Deleuze and Guattari's conception of intensity in
      its relation to common sense and to schizophrenia. According to this conception
      (a), intensity is the condition of possibility and limit for the sensible; (b) it
      becomes covered over by the organizing principles of common sense, which make our
      affects more workable and recognizable; and (c) this process of organization must
      hang together with the codification of desire through Oedipus, the main
      organizational principle of the socius. On the back of these theoretical
      considerations, I will explain what it means to say that the schizophrenic lives
      amongst intensities: (a) this involves a lack of codification of desire and thus
      of common sense, meaning an absence of organizational principles; and (b) this
      perspective leads to a different understanding of the schizophrenic's experience
      and expression, with very concrete implications for a clinical approach to
      schizophrenia.

PMID- 30239116
TI  - Immediate versus delayed exercise in men initiating androgen deprivation: effects
      on bone density and soft tissue composition.
AB  - OBJECTIVES: To examine whether it is more efficacious to commence exercise
      medicine in men with prostate cancer at the onset of androgen-deprivation therapy
      (ADT) rather than later on during treatment to preserve bone and soft-tissue
      composition, as ADT results in adverse effects including: reduced bone mineral
      density (BMD), loss of muscle mass, and increased fat mass (FM). PATIENTS AND
      METHODS: In all, 104 patients with prostate cancer, aged 48-84 years initiating
      ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise
      (DEL, n = 50) conditions. The former consisted of 6 months of supervised
      resistance/aerobic/impact exercise and the latter comprised 6 months of usual
      care followed by 6 months of the identical exercise programme. Regional and whole
      body BMD, lean mass (LM), whole body FM and trunk FM, and appendicular skeletal
      muscle (ASM) were assessed by dual X-ray absorptiometry, and muscle density by
      peripheral quantitative computed tomography at baseline, and at 6 and 12 months.
      RESULTS: There was a significant time effect (P < 0.001) for whole body, spine
      and hip BMD with a progressive loss in the IMEX and DEL groups, although lumbar
      spine BMD was largely preserved in the IMEX group at 6 months compared with the
      DEL group (-0.4% vs -1.6%). LM, ASM, and muscle density were preserved in the
      IMEX group at 6 months, declined in the DEL group at 6 months (-1.4% to -2.5%)
      and then recovered at 12 months after training. FM and trunk FM increased (P <
      0.001) over the 12-month period in the IMEX (7.8% and 4.5%, respectively) and DEL
      groups (6.5% and 4.3%, respectively). CONCLUSIONS: Commencing exercise at the
      onset of ADT preserves lumbar spine BMD, muscle mass, and muscle density. To
      avoid treatment-related adverse musculoskeletal effects, exercise medicine should
      be prescribed and commenced at the onset of ADT.

PMID- 30239117
TI  - Intra-operative imaging of surgical margins of canine soft tissue sarcoma using
      optical coherence tomography.
AB  - Optical coherence tomography (OCT) is a rapid non-invasive imaging technique that
      has shown high sensitivity for intra-operative surgical margin assessment in
      human breast cancer clinical trials. This promising technology has not been
      evaluated in veterinary medicine. The objective of this study was to correlate
      normal and abnormal histological features with OCT images for surgical margins
      from excised canine soft tissue sarcoma (STS) and to establish image evaluation
      criteria for identifying positive surgical margins. Fourteen client-owned dogs
      underwent surgical resection of a STS and OCT imaging of 2 to 4 areas of interest
      on the resected specimen were performed. Following imaging these areas were
      marked with surgical ink and trimmed for histopathology evaluation. Results
      showed that different tissue types had distinct characteristic appearances on OCT
      imaging. Adipose tissue exhibited a relatively low scattering and a honey-comb
      texture pattern. Skeletal muscle and sarcoma tissue were both dense and highly
      scattering. While sarcoma tissue was highly scattering, it did not have organized
      recognizable structure in contrast to muscle which showed clear fibre alignment
      patterns. In this investigation, we showed different tissue types had different
      and characteristic scattering and image texture appearances on OCT, which closely
      correlate with low-power histology images. Given the differentiation between
      tissue types the results support that OCT could be used to identify positive
      surgical margins immediately following resection of STS. Further research is
      needed to assess the diagnostic accuracy of this method for surgical margin
      assessment.

PMID- 30239118
TI  - Fabrication of Sub-Micrometer-Sized MoS2 Thin-Film Transistor by Phase Mode AFM
      Lithography.
AB  - The phase mode atomic force microscopy (AFM) lithography and monolayer lift-off
      process are combined to fabricate electronics based on 2D materials (2DMs), which
      remove the need for pre-fabricating markers and increase the accuracy of the
      overlay and alignment. The promising phase mode of AFM lithography eliminates the
      drawbacks of the conventional force mode such as the over-cut, under-cut, debris
      effect, and severe tip wear. The planar size of MoS2 thin-film transistors is
      shrunken down to sub-micrometer by the proposed method, and the fabricated
      devices demonstrate n-type characteristics. It offers a more flexible and easier
      way to fabricate prototypes of sub-micrometer-sized 2DMs based devices, and gives
      the opportunity to explore the size effect on the performance of 2DMs devices.

PMID- 30239119
TI  - Development and Preliminary Validation of a Depression Assessment Tool for
      Maintenance Hemodialysis Patients.
AB  - Patients undergoing maintenance hemodialysis (MHD) are subject to a higher-than
      usual prevalence of depressive disorders. However, the lack of consensus
      regarding the best assessment method remains an important problem. Thus, there is
      a clear need for more effective screening tools and an easily administered,
      disease-specific self-report measure of depression in MHD patients. After we
      developed and administered an initial depression inventory for MHD patients (I-DI
      MHD), we created the DI-MHD and administered the DI-MHD and the Beck Depression
      Inventory (BDI) to 354 patients from four hospitals. Reliability, construct
      validity and receiver operator characteristic curves were assessed. The 17-item
      DI-MHD instrument displayed good internal consistency (Cronbach's alpha =0.893),
      provided excellent convergent validity, and correlated with the BDI scale (kappa
      =0.785, P <0.001). A factor analysis pattern matrix analysis showed that a four
      factor model provided the best account of the data. Finally, the DI-MHD cutoff
      yielded a sensitivity of 0.97 and a specificity of 0.86, which were slightly
      better than the corresponding values for the BDI. The DI-MHD scale shows
      reasonable validity and reliability for assessing depression in MHD patients.

PMID- 30239120
TI  - Size, Shape, and Protein Corona Determine Cellular Uptake and Removal Mechanisms
      of Gold Nanoparticles.
AB  - Size, shape, and protein corona play a key role in cellular uptake and removal
      mechanisms of gold nanoparticles (Au NPs). The 15 nm nanoparticles (NP1), the 45
      nm nanoparticles (NP2), and the rod-shaped nanoparticles (NR) enter into cells
      via a receptor-mediated endocytosis (RME) pathway. The star-shaped nanoparticles
      (NS) adopt not only clathrin-mediated, but also caveolin-mediated endocytosis
      pathways. However, the 80 nm nanoparitcles (NP3) mainly enter into the cells by
      macropinocytosis pathway due to the big size. Furthermore, the results indicate
      that the presence of protein corona can change the uptake mechanisms of Au NPs.
      The endocytosis pathway of NP1, NP2, and NS changes from RME to macropinocytosis
      pathway and NR changes from RME to clathrin and caveolin-independent pathway
      under the non-fetal bovine serun (FBS)-coated condition. Both FBS-coated and non
      FBS-coated of five types of Au NPs are released out through the lysosomal
      exocytosis pathway. The size, shape, and protein corona have an effect on the
      exocytosis ratio and amount, but do not change the exocytosis mechanism. The
      systematic study of the endocytosis and exocytosis mechanism of Au NPs with
      different sizes and shapes will benefit the toxicology evaluation and
      nanomedicine application of Au NPs.

PMID- 30239121
TI  - New Dihydrostilbene Derivatives from Chloraea chrysantha.
AB  - The study of the main components of the alcoholic extract obtained from Chloraea
      chrysantha Poepp. led to the isolation of two new dihydrostilbene derivatives
      together with the known gavilein (3). The new compounds have been assigned as 3
      methoxy-5-{2-[3-methoxy-2-(3-methylbut-2-en-1-yl)phenyl]ethyl}phenol (1) and 1-[2
      (3,5-dimethoxyphenyl)ethyl]-3-methoxy-2-(3-methylbut-2-en-1-yl)benzene (2). The
      presence of compounds 1-3 is perfectly in accordance with the current botanical
      classification of the genus.

PMID- 30239122
TI  - Exposure to herbicides reduces larval sensitivity to insecticides in Spodoptera
      litura (Lepidoptera: Noctuidae).
AB  - Herbicides and insecticides are widely used in modern agriculture. It has been
      reported in various studies that application of insecticides can increase
      tolerance of herbivorous insects to insecticides. However, limited information
      exists on susceptibility to insecticides when insects are exposed to herbicides.
      This study was conducted to investigate the potential impact of the herbicides
      trifluralin and 2-methyl-4-chlorophenoxyacetic acid sodium salt (MCPA-Na) on the
      susceptibility of the nocturnal moth Spodoptera litura to the insecticides lambda
      cyhalothrin, phoxim and bifenthrin. We found that larvae exposed to trifluralin
      or MCPA-Na became significantly less susceptible to both insecticides than non
      exposed control larvae. Herbicide-treated larvae did not show altered growth
      under the used test conditions. However, heads of herbicide-treated larvae showed
      increased expression of the acetylcholinesterase genes SlAce1 and SlAce2.
      Moreover, the fat body and midgut of herbicide-treated larvae displayed elevated
      expression of detoxification genes (the carboxylesterase gene SlCarE; the
      glutathione S-transferase genes SlGSTe2 and SlGSTe3; the cytochrome P450
      monooxygenase genes CYP6B48, CYP9A40 and CYP321B1). The CYP6B48 gene exhibited
      highest inducibility. In conclusion, the data of this study suggest that exposure
      of S. litura larvae to herbicides may stimulate detoxification mechanisms that
      compromise the efficacy of insecticides.

PMID- 30239123
TI  - Oxygen-Doped Nickel Iron Phosphide Nanocube Arrays Grown on Ni Foam for Oxygen
      Evolution Electrocatalysis.
AB  - A rationally designed oxygen evolution reaction (OER) catalyst with advanced
      structural and compositional superiority is highly desirable to optimize
      electrocatalytic performance. Prussian blue analogues (PBAs) with adjustable
      element compositions and accessible porous structures represent a promising
      precursor for the preparation of OER catalysts. Herein, oxygen-doped nickel iron
      phosphide nanocube arrays (Ni2 P/(NiFe)2 P(O) NAs) grown on Ni foam is rationally
      designed and fabricated from PBAs. The porous structure and the synergistic
      effect of Ni and Fe enable superior electrocatalytic performance and stability
      toward the OER in alkaline electrolytes. Density functional theory calculations
      reveal that Fe-incorporated Ni2 P can generate new active sites on the Fe atoms,
      and the energy barriers of the intermediates and products are decreased
      efficiently in the presence of surface doped oxygen, both processes are crucial
      factors for enhanced catalytic performances. In 1 m KOH, the Ni2 P/(NiFe)2 P(O)
      NAs afford current densities of 10 and 800 mA cm-2 at overpotentials of 150 and
      530 mV, respectively, which outperform the commercial noble metal IrO2 . Ni2
      P/(NiFe)2 P(O) NAs also have long-term stability over 100 h at a high current
      density. The present approach may provide a new avenue for the controlled
      assembly of nanoarrays for energy storage and conversion applications.

PMID- 30239124
TI  - Single-Molecule Co-Immunoprecipitation Reveals Functional Inheritance of EGFRs in
      Extracellular Vesicles.
AB  - Cancer cells actively release extracellular vesicles (EVs) as important carriers
      of cellular information to tumor microenvironments. Although the composition and
      quantity of the proteins contained in EVs are characterized, it remains unknown
      how these proteins in EVs are related to those in the original cells at the
      functional level. With epidermal growth factor receptor (EGFR) in lung
      adenocarcinoma cells as a model oncoprotein, it is studied how distinct types of
      EVs, microvesicles and exosomes, represent their original cells at the protein
      and protein-protein interaction (PPI) level. Using the recently developed single
      molecule immunolabeling and co-immunoprecipitation schemes, the quantity and PPI
      strengths of EGFRs derived from EVs and the original lung adenocarcinoma cells
      are determined. It is found that the microvesicles exhibit higher correlations
      with the original cells than the exosomes in terms of the EGFR levels and their
      PPI patterns. In spite of these detailed differences between the microvesicles
      and exosomes, the EGFR PPI strengths measured for EVs generally show a tight
      correlation with those determined for the original cells. The results suggest
      that EGFRs contained in EVs closely reflect the cellular EGFR in terms of their
      downstream signaling capacity.

PMID- 30239125
TI  - Determination of siloxanes in water samples employing graphene oxide/Fe3 O4
      nanocomposite as sorbent for magnetic solid-phase extraction prior to GC-MS.
AB  - A new, fast, simple, and environmentally friendly analytical method has been
      developed to determine six siloxanes in water samples: octamethyltrisiloxane,
      octamethylcyclotetrasiloxane, decamethyltetrasiloxane,
      decamethylcyclopentasiloxane, dodecamethylpentasiloxane and
      dodecamethylcyclohexasiloxane. The analytical method consists of magnetic solid
      phase extraction employing graphene oxide/Fe3 O4 as sorbent for the separation
      and preconcentration of siloxanes prior to GC-MS determination. The extraction
      procedure was optimized by means of a Plackett-Burman design. Under the optimized
      extraction conditions (graphene oxide/Fe3 O4 , 20 mg; extraction time, 10 min;
      eluent volume, 0.5 mL ACN; elution time, 2.5 min; sample volume, 20 mL), the
      method rendered repeatability levels with a relative standard deviation between 9
      and 20% (n = 6, 10 MUg/L). Methodological limits of detection ranged from 0.003
      to 0.1 MUg/L. The linearity of the method was studied between the methodological
      limit of quantification and 100 MUg/L, obtaining correlation coefficient values
      between 0.990 and 0.999. The applicability of the method was assessed by
      analyzing drinking, river and wastewater samples. Relative recovery values ranged
      between 70 and 120% (1 and 60 MUg/L spiking level) showing that the matrix had a
      negligible effect on extraction. Finally, the greenness of this method was
      confirmed by the semiquantitative Eco-Scale metrics.

PMID- 30239126
TI  - The physiological roles of autophagy in the mammalian life cycle.
AB  - Autophagy is primarily an efficient intracellular catabolic pathway used for
      degradation of abnormal cellular protein aggregates and damaged organelles.
      Although autophagy was initially proposed to be a cellular stress responder,
      increasing evidence suggests that it carries out normal physiological roles in
      multiple biological processes. To date, autophagy has been identified in most
      organs and at many different developmental stages, indicating that it is not only
      essential for cellular homeostasis and renovation, but is also important for
      organ development. Herein, we summarize our current understanding of the
      functions of autophagy (which here refers to macroautophagy) in the mammalian
      life cycle.

PMID- 30239127
TI  - Uveitis causes according to immune status of patients.
AB  - PURPOSE: The advances in medicine have led to an increased number of people
      living with some form of immunodeficiency. Most ocular infections in
      immunocompromised patients may lead to irreversible blindness. We identify the
      causes of uveitis in immunocompetent and immunocompromised patients. METHODS: A
      retrospective cohort study of 1354 consecutive patients. All patients underwent a
      standard work-up for uveitis. RESULTS: An immunocompromised state was identified
      in 171/1354 patients (13%), of whom 40 had Human immunodeficiency virus (HIV)
      infection, 52 received immunosuppressive medications, 28 had concurrent malignant
      disorder and 20 had other causes for their immunosuppression. In addition,
      93/1354 patients (7%) had diabetes mellitus (DM). The prevalence of intraocular
      infections was much higher in immunocompromised patients than in immunocompetent
      patients and DM (p < 0.001). Causes of uveitis differed between the diverse
      immunocompromised groups. The non-HIV immunocompromised patients showed primarily
      intraocular herpes simplex and varicella zoster virus infections, whilst HIV
      positive patients exhibited frequently cytomegalovirus (CMV) retinitis and
      syphilis. Patients with generalized malignancies were characterized by a lower
      prevalence of infections and higher prevalence of sarcoidosis. Patients with DM
      typically showed sarcoidosis and bacterial intraocular infections. The percentage
      of undetermined uveitis diagnoses was markedly lower in immunosuppressed patients
      (p < 0.001). CONCLUSION: In immunocompromised patients with uveitis, infections
      were diagnosed in 46% of cases in contrast to 12% in the immunocompetent
      patients. The causes of uveitis differed among the various types of
      immunosuppression. Immunocompromised patients with uveitis require a rapid
      assessment for the most expected infections.

PMID- 30239128
TI  - A Concise Synthesis of Potential COX Inhibitor BRL-37959 and Analogs Involving
      Bismuth(III) Catalyzed Friedel-Crafts Acylation.
AB  - We report the development of a concise method of synthesizing possible
      cyclooxygenase (COX) inhibitor BRL-37959, which is believed to be a potent
      nonsteroidal anti-inflammatory drug (NSAID). The four-step synthesis greatly
      increased the efficiency of compound production from commercially available
      salicylaldehydes. The synthesis involved an optimized, bismuth(III)
      trifluoromethanesulfonate catalyzed benzoylation of a benzofuran ring.

PMID- 30239129
TI  - Electrochemical Deposition Tailors the Catalytic Performance of MnO2 -Based
      Micromotors.
AB  - Artificial micro/nanomotors that could perform diverse tasks autonomously at the
      micro/nanoscale have been emerging as promising tools in many practical
      applications. Electrochemical synthesis is one of the dominating methods to
      fabricate these micro/nanodevices with diverse geometries and material
      components. By changing the conditions of electrochemical deposition, the surface
      morphology, crystal structure, and hence the resultant performance of deposited
      material could be tailored. In the current work, a feasible fabrication strategy
      is presented in terms of three unique electrodeposition types (i.e.,
      potentiodynamic, potentiostatic (PS), and galvanostatic) to synthesize different
      MnO2 -based micromotors. Distinct propulsion behavior as well as the catalytic
      degradation of azo-dye organic waste (with methylene blue as the representative),
      between three kinds of MnO2 -based micromotors is clearly displayed, owing to the
      distinctive chemical composition and morphology designs. The activated R-MnO2 
      based micromotors in PS mode exhibit fast motion speed (up to 12 body length per
      second), leading to the highest degradation efficiency. Such propulsion
      performance is comparable with the microrockets made by noble metals such as Pt
      and Ag. The new protocol will have a profound impact on the design of synthetic
      micro/nanomotors and hold a considerable promise for their diverse applications.

PMID- 30239130
TI  - Scalable Multiplexed Drug-Combination Screening Platforms Using 3D Microtumor
      Model for Precision Medicine.
AB  - Cancer heterogeneity is a notorious hallmark of this disease, and it is desirable
      to tailor effective treatments for each individual patient. Drug combinations
      have been widely accepted in cancer treatment for better therapeutic efficacy as
      compared to a single compound. However, experimental complexity and cost grow
      exponentially with more target compounds under investigation. The primary
      challenge remains to efficiently perform a large-scale drug combination screening
      using a small number of patient primary samples for testing. Here, a scalable,
      easy-to-use, high-throughput drug combination screening scheme is reported, which
      has the potential of screening all possible pairwise drug combinations for
      arbitrary number of drugs with multiple logarithmic mixing ratios. A "Christmas
      tree mixer" structure is introduced to generate a logarithmic concentration
      mixing ratio between drug pairs, providing a large drug concentration range for
      screening. A three-layer structure design and special inlets arrangement
      facilitate simple drug loading process. As a proof of concept, an 8-drug
      combination chip is implemented, which is capable of screening 172 different
      treatment conditions over 1032 3D cancer spheroids on a single chip. Using both
      cancer cell lines and patient-derived cancer cells, effective drug combination
      screening is demonstrated for precision medicine.

PMID- 30239131
TI  - Re: Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation:
      Toxicity reporting of magnesium sulphate in management of pre-eclampsia/eclampsia
      an unresolved clinical and research issue.

PMID- 30239132
TI  - Facile synthesis of titanium(IV) ion-immobilized poly-glycidyl methacrylate
      microparticles functionalized with polyethylenimine and adenosine triphosphate
      for highly specific enrichment of intact phosphoproteins.
AB  - In this study, a facile synthesis of the titanium(IV) ion-immobilized poly
      glycidyl methacrylate microparticles functionalized with polyethylenimine and
      adenosine triphosphate was developed for efficient enrichment of intact
      phosphoproteins. The titanium(IV) ion-immobilized microparticles had higher
      saturated adsorption capacity for phosphoproteins (1217.6 mg/g for beta-casein)
      than nonphosphoproteins (97.1 mg/g for bovine serum albumin) and the average
      particle diameter was about 1.4 MUm with good dispersibility. In application, as
      demonstrated by SDS-PAGE, titanium(IV) ion-immobilized microparticles exhibited
      good performance in enriching intact phosphoproteins from standard protein
      mixtures of beta-casein and bovine serum albumin with high specificity and
      selectivity. In addition, titanium(IV) ion-immobilized microparticles were also
      successfully applied in intact phosphoprotein enrichment from complex biological
      samples including nonfat milk, chicken egg white, and mouse heart tissue extract.

PMID- 30239133
TI  - Renal arteriovenous fistula induced by extracorporeal shock wave lithotripsy
      treated by retroperitoneoscopic nephrectomy.
AB  - Renal arteriovenous fistula (AVF) is a rare but potentially severe and life
      threatening entity. It can occur after various invasive renal interventions,
      including resection of a localized renal tumor, renal biopsy, percutaneous renal
      surgery, and even blunt injury of the kidney. The time of clinical presentation
      of a renal AVF is variable and may occur decades after the injury originally
      occurred. Here, we report a case of renal AVF induced by extracorporeal shock
      wave lithotripsy 11 years earlier in an asymptomatic 72-year-old woman. Given the
      patient's pre-existing hemodialysis dependence, retroperitoneoscopic nephrectomy
      was performed. On the basis of patient's clinical history, the location of the
      renal AVF, and the pathological diagnosis, we suggested that renal AVF was a late
      consequence of the injury to the intrarenal vessels induced by extracorporeal
      shock wave lithotripsy.

PMID- 30239134
TI  - Effect of multidisciplinary cardiac rehabilitation on the response to cardiac
      resynchronization therapy.
AB  - BACKGROUND: Both cardiac resynchronization therapy (CRT) and Multidisciplinary
      Cardiac Rehabilitation (CR) beneficially influence symptomatic status, exercise
      capacity, quality of life, and heart failure readmission rates. However, the
      interaction between both therapies remain incompletely addressed. METHODS:
      Consecutive CRT patients implanted in a single tertiary care center were
      retrospectively analyzed. Patients were dived according to the participation in a
      structured CR-program following CRT-implant. The effect on functional status (New
      York Heart Association; NYHA-class), reverse remodeling (change in left
      ventricular ejection fraction; LVEF), and the combined endpoint of heart failure
      readmission and all-cause mortality was assessed after multivariate correction.
      RESULTS: A total of 655 patients were analyzed of whom 223(34%) did and 432(66%)
      did not participate in a structured multidisciplinary CR-program following
      implant. No adverse events relating to exercise training occurred during the CR
      program. Patients who participated in the CR-program had a more pronounced
      improvement in NYHA-class at 6-months (P = 0.006), even after multivariate
      correction (beta = -0.144; 95% CI = [-0.270; -0.018]; P = 0.025). Maximal
      workload and VO2max on CPET at 6 months improved significantly even after
      adjustment (P < 0.001, respectively P = 0.017). At 6-months, CR associated with
      more improvement in LVEF (+11.9 +/- 13 vs +14.5 +/- 11; P = 0.008), however, this
      relationship was lost after multivariate correction (P = 0.136). During 36 +/- 22
      months follow-up, patients in the CR group had a higher event-free survival for
      the combined endpoint (P = 0.001), even after multivariate correction (adjusted
      HR = 0.547; CI = 0.366-0.818; P = 0.003). CONCLUSIONS: Following CRT-implant, the
      participation in a structured CR-program is safe and beneficially influences
      symptomatic response and clinical outcome. The beneficial effects of exercise
      training are potentially independent and additive to the beneficial reverse
      remodeling effect induced by CRT itself.

PMID- 30239135
TI  - Enigmatic ear stones: what we know about the functional role and evolution of
      fish otoliths.
AB  - Otoliths in bony fishes play an important role in the senses of balance and
      hearing. Otolith mass and shape are, among others, likely to be decisive factors
      influencing otolith motion and thus ear functioning. Yet our knowledge of how
      exactly these factors influence otolith motion is incomplete. In addition,
      experimental studies directly investigating the function of otoliths in the inner
      ear are scarce and yield partly conflicting results. Herein, we discuss questions
      and hypotheses on how otolith mass and shape, and the relationship between the
      sensory epithelium and overlying otolith, influence otolith motion. We discuss
      (i) the state-of-the-art knowledge regarding otolith function, (ii) gaps in
      knowledge that remain to be filled, and (iii) future approaches that may improve
      our understanding of the role of otoliths in ear functioning. We further link
      these functional questions to the evolution of solid teleost otoliths instead of
      numerous tiny otoconia as found in most other vertebrates. Until now, the
      selective forces and/or constraints driving the evolution of solid calcareous
      otoliths and their diversity in shape in teleosts are largely unknown. Based on a
      data set on the structure of otoliths and otoconia in more than 160 species
      covering the main vertebrate groups, we present a hypothetical framework for
      teleost otolith evolution. We suggest that the advent of solid otoliths may have
      initially been a selectively neutral 'by-product' of other key innovations during
      teleost evolution. The teleost-specific genome duplication event may have paved
      the way for diversification in otolith shape. Otolith shapes may have evolved
      along with the considerable diversity of, and improvements in, auditory abilities
      in teleost fishes. However, phenotypic plasticity may also play an important role
      in the creation of different otolith types, and different portions of the otolith
      may show different degrees of phenotypic plasticity. Future studies should thus
      adopt a phylogenetic perspective and apply comparative and methodologically
      integrative approaches, including fossil otoliths, when investigating
      otoconia/otolith evolution and their function in the inner ear.

PMID- 30239136
TI  - The prevalence and psychosocial risk factors for psychotic-like experiences (PLE)
      among high school students in Jakarta.
AB  - INTRODUCTION: The prevalence of psychotic-like experiences (PLE) in general
      population is moderately high (5%-8%), although the prevalence of psychotic
      disorder is considerably low (?1%). Amid the urgency to understand the underlying
      factors of psychotic disorder and PLE, most research tend to focus on genetic
      factors. However, numerous recent works suggested increasing importance of non
      genetic factors. This study aims to investigate the prevalence of PLE and any
      psychosocial variables that contribute to any occurrence of PLE among adolescent
      in Jakarta. METHODS: This is a school based cross-sectional study that was
      carried out in early 2017. A total sample of 623 high school students from five
      schools in Jakarta were selected by using multistage random sampling. Psychotic
      experience was measured using Psychotic-Like Experiences Questionnaire. Multiple
      psychosocial variables proposed as predictor model for PLE were examined using
      multivariate regression. RESULTS: Our final result showed 20.6% prevalence of PLE
      among high school students in Jakarta. The proposed psychosocial risk model
      (consisting of violence exposure, parental communication pattern, peer and
      conduct problems, social comparison, parental attachment, loneliness, and
      bullying) contributed to explain 16.3% of the occurrence of PLE (R square: .163).
      DISCUSSION: The prevalence of PLE in this population was considerably high.
      Cultural factors such as paranormal beliefs are assumed to contribute to the high
      prevalence of PLE among high school students. The quite low contribution score of
      psychosocial model proposed in predicting the phenomenon of PLE shows that
      further research is needed to explore more variables that can be better
      predictors of PLE.

PMID- 30239137
TI  - Linking of metabolomic biomarkers with cardiometabolic health in Chinese
      population.
AB  - Due to rapid nutrition transitions, the prevalence of cardiometabolic diseases,
      such as metabolic syndrome, type 2 diabetes, and cardiovascular diseases, has
      been increasing at an alarming rate in the Chinese population. Moreover, Asians,
      including Chinese, have been hypothesized to have a higher susceptibility to
      cardiometabolic diseases than Caucasians. Early prediction and prevention are key
      to controlling this epidemic trend; to this end, the identification of novel
      biomarkers is critical to reflect environmental exposure, as well as to reveal
      endogenous metabolic and pathophysiologic mechanisms. The emerging "omics"
      technologies, especially metabolomics, offer a unique opportunity to provide
      novel signatures or fingerprints to understand the effects of genetic and non
      genetic factors on cardiometabolic health. During the past two decades,
      metabolomic approaches have been increasingly used in various epidemiological
      studies, primarily in Western populations. Although the field is still in its
      early stages, some studies have tried to identify novel compounds or confirm
      their metabolites and associations with cardiometabolic diseases in Chinese
      populations, including amino acids, fatty acids, acylcarnitines and other
      metabolites. Despite major efforts to discover novel biomarkers for disease
      prediction or intervention, the limits in current study design, analytical
      platforms, and data processing approaches are challenges in metabolomic research
      worldwide. Therefore, future research with more advanced technologies, rigorous
      study designs, standardized detection and analytic approaches, and integrated
      data from multiomics approaches are essential to evaluate the feasibility of
      using metabolomics in clinical settings. Finally, the functional roles and
      underlying biological mechanisms of metabolomic biomarkers should be elucidated
      by future mechanistic research.

PMID- 30239139
TI  - Argon laser peripheral iridoplasty for chronic primary angle-closure and angle
      closure glaucoma in caucasians.
AB  - PURPOSE: To investigate whether the peripheral thinning and shrinking of the iris
      as induced with Argon laser peripheral iridoplasty (ALPI) has an effect on
      intraocular pressure (IOP), angle structure and 3-D anterior segment (AS)
      morphology in Caucasians with chronic primary angle-closure (PAC) and primary
      angle-closure glaucoma (PACG). METHODS: Twenty-four eyes of 24 patients (age 67.7
      +/- 8.9 years; seven males; 17 females) diagnosed with PAC (n = 10) or PACG (n =
      14) were assigned for ALPI prior to laser peripheral iridotomy (LPI) and
      consecutively enrolled in this prospective interventional study. Intraocular
      pressure (IOP) was measured with Goldmann applanation tonometry, angle structure
      with gonioscopy using the Shaffer grading system and AS morphology with the
      Pentacam rotating Scheimpflug camera prior to and 3 months after ALPI.
      Intraocular pressure (IOP)-lowering medication was not changed during follow-up.
      RESULTS: Intraocular pressure (IOP) changed statistically significantly from 18.8
      +/- 3.6 to 14.7 +/- 3.1 mmHg (p < 0.001). Gonioscopy showed a statistically
      significant angle widening in all four quadrants: nasally from Shaffer 1.04 +/-
      0.98 to 2.54 +/- 1.1 (p < 0.001), superiorly from 0.39 +/- 0.66 to 1.58 +/- 1.21
      (p < 0.001), temporally from 0.87 +/- 1.01 to 2.17 +/- 1.24 (p = 0.001) and
      inferiorly from 1.22 +/- 0.74 to 2.75 +/- 0.9 (p < 0.001). Pentacam parameters
      like anterior chamber depth, volume and angle did not increase statistically
      significantly. CONCLUSION: Argon laser peripheral iridoplasty (ALPI) is a safe
      and effective procedure for reducing appositional angle-closure and thus IOP in
      nonacute PAC and PACG patients.

PMID- 30239138
TI  - Levels of oxidative DNA damage are low in ex vivo engineered human limbal
      epithelial tissue.
AB  - PURPOSE: To examine levels of oxidative DNA base damage and expression of
      selected genes and proteins related to DNA damage repair in human limbal
      epithelium engineered ex vivo. METHODS: Cells were expanded from limbal tissue on
      cell culture-treated inserts in medium containing fetal bovine serum, recombinant
      growth factors, hormones and cholera toxin (COM) and in medium with human serum
      as the single growth-promoting additive (HS). Cells were analysed after two,
      three and four weeks in culture for DNA strand breaks and oxidized purine bases
      (Comet assay using the enzyme formamidopyrimidine DNA glycosylase, Fpg) and for
      expression of DNA repair enzymes APE1, OGG1 and Polbeta by in situ hybridization
      (ISH) and by immunohistochemistry (IHC). RESULTS: Levels of strand breaks were
      substantial while levels of net Fpg-sensitive sites (8-oxoguanine and ring-opened
      FaPy bases) were relatively low in cells engineered in COM and in HS. Both types
      of medium were found to support expression of base excision repair (BER) enzymes
      APE1, OGG1 and Polbeta at the gene level. At the protein level, expression of
      APE1 and OGG1 was noticeable in both conditions while expression of Polbeta was
      low. CONCLUSION: Our findings indicate low levels of oxidative stress and/or
      efficient DNA purine base damage repair in human limbal epithelium engineered in
      a medium with human serum as the single growth-promoting additive as well as in
      traditional medium with xenobiotics.

PMID- 30239140
TI  - Primary angle closure and primary angle closure glaucoma in retinal vein
      occlusion.
AB  - PURPOSE: To investigate the frequency of primary angle closure (PAC) and primary
      angle closure glaucoma (PACG) in patients with retinal vein occlusion (RVO) based
      on a hospital population. METHODS: A total of 375 consecutive cases newly
      diagnosed with RVO by fluorescein fundus angiography at a single eye centre in
      Peking were reviewed. Gonioscopy was performed in all patients. Glaucoma was
      diagnosed according to the criteria of the International Society of Geographical
      and Epidemiological Ophthalmology. Retinal vein occlusion was classified as
      central retinal vein occlusion (CRVO), hemicentral retinal vein occlusion (HRVO),
      or branch retinal vein occlusion (BRVO), and as arteriovenous crossing RVO (AV
      RVO), optic cup RVO (OC-RVO), optic nerve RVO without optical nerve head swelling
      (NONHS-RVO), or RVO with optical nerve head swelling (ONHS-RVO) based on the site
      of venous occlusion. Percentage of PAC or PACG for each type of RVO were
      calculated. RESULTS: PACG had a frequency of 4.1% [95% confidence interval (CI)
      2.2-6.9%] in 317 RVO patients [5.3% (95% CI 2.0-11.2%) in CRVO, 8.8% (95% CI 1.9
      23.7%) in HRVO, and 1.9% (95% CI 0.4-5.4%) in BRVO]. Primary angle closure (PAC)
      had a frequency of 2.9% (95% CI 1.4-5.5%) in RVO. PAC/PACG had a frequency of
      11.5% (95% CI 6.3-18.9%) in CRVO, 8.8% (95% CI 1.9-23.7%) in HRVO and 3.1% (95%
      CI 1.0-7.1%) in BRVO. PAC/PACG was significantly more prevalent in NONHS-RVO
      [18.9% (95% CI 9.4-32.0%)] than in ONHS-RVO [6.5% (95% CI 2.1-14.5%)], AV-RVO
      [3.1% (95% CI 0.9-7.8%)], and OC-RVO [2.3% (95% CI 0.1-12.3%)]. CONCLUSION: The
      overall frequency of PAC/PACG was much higher in patients with RVO (especially
      CRVO) than that in the general population. Eyes with PAC/PACG may undergo
      mechanical changes in the lamina cribrosa of the optic disc, resulting in RVO.
      Angle-closure conditions should be borne in mind when investigating Chinese
      patients with RVO.

PMID- 30239141
TI  - Plasma Exchange Downregulates Activated Monocytes and Restores Regulatory T Cells
      in Kawasaki Disease.
AB  - In Kawasaki disease (KD), the effect of plasma exchange (PE) on immune cells has
      not been fully elucidated. Therefore, we examined the changes in the number of
      CD14+ CD16+ activated monocytes, regulatory T (Treg ), and T-helper type 17
      (Th17) cells in KD patients treated with PE. The percentage of total monocytes
      and subclasses of lymphocytes, including CD4+ and CD8+ T cells, and CD19+ B
      cells, showed no significant difference before and after PE. However, the
      percentage of CD14+ CD16+ monocytes in total leukocytes decreased significantly
      after PE (1.1% +/- 1.5% vs. 2.1% +/- 2.3%, P < 0.05). Furthermore, while the
      percentage of Th17 cells in CD4+ T cells did not change, the percentage of Treg
      cells in CD4+ T cells increased significantly after PE (11.1% +/- 5.1% vs. 8.0%
      +/- 4.4%, P < 0.05). Therefore, PE downregulates activated monocytes and
      upregulates Treg cells toward normal levels and thus attenuates inflammation in
      KD.

PMID- 30239143
TI  - Association of Low Serum Potassium Levels and Risk for All-Cause Mortality in
      Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.
AB  - Dyskalemia is a risk factor for mortality in patients without CKD, but the effect
      of hypokalemia in patients with CKD remains uncertain. PubMed, Embase, Cochrane,
      and Ovid databases were searched from inception to December 31, 2017 for studies
      that reported all-cause and cardiovascular mortality or events in patients with
      CKD (any stage). Pooled hazard ratios (HR) and corresponding 95% CI were
      calculated. A total of 11 clinical studies enrolling 57 234 subjects with CKD
      were included in the meta-analysis. Compared with control serum potassium (SK)
      levels, low SK (SK <4.0 mEq/L) was associated with higher risk of all-cause
      mortality in a random-effects model (HR = 1.57; 95% CI: 1.25-1.97). Moderate low
      SK (<3.5 mEq/L) increased risk of all-cause mortality by 105%. Mild low SK
      (3.5~4.0 mEq/L) also increased all-cause mortality risk (HR = 1.18, 95% CI: 1.11
      1.26). Low SK was also associated with increased cardiovascular mortality (HR =
      1.40, 95% CI: 1.22-1.62) and ESRD risk (HR = 1.35, 95% CI: 1.18-1.54). SK <4.0
      mEq/L was associated with higher mortality risk in CKD patients, especially in
      those with SK <3.5 mEq/L. Additional prospective studies will be necessary to
      explore this relationship, as well as whether correcting hypokalemia decreases
      mortality in patients with CKD.

PMID- 30239144
TI  - Reply to Petals and thorns in programmed death-ligand 1 testing: Is all non-small
      cell lung cancer diagnostic material suitable?

PMID- 30239142
TI  - Changes in peripapillary choroidal thickness in patients with multiple sclerosis.
AB  - PURPOSE: To study peripapillary choroidal thickness (PPCT) around the optic disc
      and establish zones using a new swept source optical coherence tomography (SS
      OCT) device. To evaluate PPCT differences between patients with multiple
      sclerosis (MS) and age- and sex-matched healthy controls. METHODS: A total of 102
      healthy subjects and 51 patients with MS were consecutively recruited. Healthy
      subjects were divided into teaching (n = 51, used to establish choroidal zones)
      and validating (n = 51, used to compare measurements with MS patients)
      populations. An optic disc 6.0 * 6.0-mm three-dimensional scan was obtained using
      SS-OCT Triton. A 26 * 26 cube-grid centred on the optic disc was generated
      automatically to measure PPCT. Four choroidal zones were established and used to
      compare PPCT between healthy controls and patients with MS. RESULTS:
      Peripapillary choroidal thickness (PPCT) was significantly thinner in patients in
      all concentric zones (p <= 0.0001): 134.02 +/- 16.59 MUm in MS group versus
      171.56 +/- 12.43 MUm in the control group in zone 2; 182.23 +/- 20.52 versus
      219.03 +/- 17.99 MUm, respectively, in zone 3; and 223.52 +/- 10.70 versus 259.99
      +/- 10.29 MUm, respectively, in zone 4. The choroidal thinning in the MS group
      tended to decrease as we distanced from the optic nerve head. Peripapillary
      choroidal thickness (PPCT) had a similar pattern in controls and MS; it was
      thicker in the superior region, followed by temporal, nasal and inferior regions.
      CONCLUSION: Patients with MS showed peripapillary choroidal thinning when
      compared with healthy subjects in all zones around the optic disc. Peripapillary
      choroidal tissue shows a concentric pattern, increasing in thickness when
      increasing the distance from the optic nerve. The new SS-OCT could be useful for
      evaluating choroidal thinning in clinical practice.

PMID- 30239145
TI  - C-Alkylation of Secondary Alcohols by Primary Alcohols through Manganese
      Catalyzed Double Hydrogen Autotransfer.
AB  - A new Mn-catalyzed alkylation of secondary alcohols with non-activated alcohols
      is presented. The use of a stable and well-defined manganese pincer complex,
      stabilized by a PNN ligand, together with a catalytic amount of base enabled the
      conversion of renewable alcohol feedstocks to a broad range of higher-value
      alcohols in good yields with water as the sole byproduct. The strategy eliminates
      the need for exogenous and detrimental alkyl halides as well as the use of noble
      metal catalysts, making the C-alkylation through double hydrogen autotransfer a
      highly sustainable and environmentally benign process. Mechanistic investigations
      support a hydrogen autotransfer mechanism in which a non-innocent ligand plays a
      crucial role.

PMID- 30239146
TI  - Petals and thorns in programmed death-ligand 1 testing: Is all non-small cell
      lung cancer diagnostic material suitable?

PMID- 30239147
TI  - Cocaine adulteration with the anthelminthic tetramisole (levamisole/dexamisole):
      Long-term monitoring of its intake by chiral LC-MS/MS analysis of cocaine
      positive hair samples.
AB  - Recent studies indicate that not only the anthelminthic levamisole but also the
      racemate tetramisole (R-/S-phenyltetraimidazothiazole, PTHIT) was found as an
      adulterant for cocaine. We herein report on the investigation of the prevalence
      of PTHIT among cocaine-positive hair samples and the discrimination of the
      presence of its stereoisomers levamisole and dexamisole. Cocaine-positive hair
      samples were collected in a forensic context in 2015 and mainly 2017 (n = 724).
      Cocaine and PTHIT concentrations have been determined by achiral liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). For distinction of
      levamisole/dexamisole chiral LC-MS/MS was performed. Cocaine hair concentrations
      ranged from 500 (cut-off) to approximately 800 000 pg/mg. The study demonstrates
      a strong prevalence of PTHIT in cocaine users' hair (87%, n = 627). PTHIT hair
      concentrations ranged from below LLOQ 3.5 to approximately 61 000 pg/mg (median:
      260 pg/mg). Surprisingly, enantiomeric ratios of levamisole/dexamisole ranged
      from 0.17 to 1.34 (median: 0.63). Therefore, PTHIT-adulterated street cocaine
      samples (n = 24) seized between 2013 and 2016 were tested. Samples mainly
      contained racemic tetramisole (87.5%), only one sample contained levamisole only
      and two samples contained non-racemic PTHIT. Our experiments suggest that the
      presence of tetramisole in biological samples may have hitherto been
      underestimated. Most probably higher dexamisole than levamisole concentrations in
      hair specimens arise from stereoselective metabolism and/or elimination. This is
      particularly important in light of the different pharmacological activities of
      the two enantiomers and potentially different adverse effects. Toxicological
      interpretations in intoxication cases with adulterated cocaine should not only
      consider levamisole but also tetramisole and terminology in scientific
      contributions should be used accordingly.

PMID- 30239148
TI  - Angular range, sampling and noise considerations for inverse light scattering
      analysis of nuclear morphology.
AB  - In recent years, significant work has been devoted to the use of angle-resolved
      elastic scattering for the extraction of nuclear morphology in tissue. By
      treating the nucleus as a Mie scattering object, techniques such as angle
      resolved low-coherence interferometry (a/LCI) have demonstrated substantial
      success in identifying nuclear alterations associated with dysplasia. Because
      optical biopsies are inherently noninvasive, only a small, discretized portion of
      the 4pi scattering field can be collected from tissue, limiting the amount of
      information available for diagnostic purposes. In this work, we comprehensively
      characterize the diagnostic impact of variations in angular sampling, range and
      noise for inverse light scattering analysis of nuclear morphology, using a
      previously reported dataset from 40 patients undergoing a/LCI optical biopsy for
      cervical dysplasia. The results from this analysis are applied to a benchtop
      scanning a/LCI system which compromises angular range for wide-area scanning
      capability. This work will inform the design of next-generation optical biopsy
      probes by directing optical design towards parameters which offer the most
      diagnostic utility.

PMID- 30239149
TI  - Acinetobacter lwoffii, an emerging pathogen for fish in Schizothorax genus in
      China.
AB  - Acinetobacter lwoffii, a serious human pathogen, has been identified as a cause
      of nosocomial infections such as bacteremia, pneumonia and meningitis. There are
      only a few studies reporting A. lwoffii as a pathogen of fish. During 2016 and
      2017, six bacterial strains, isolated from diseased fish of the Schizothorax
      genus, were identified as A. lwoffii by morphology, biochemical tests, 16S rDNA
      and gyrB gene sequencing analysis. One of these isolates was selected for
      experimental infection of Sclizothorax prenanti, Schizothorax davidi and
      Schizothorax wangchiachii, to confirm its pathogenicity. Experimentally infected
      fish showed similar symptoms to those observed in fish after natural outbreaks.
      Susceptibility of the isolates to 14 antibiotics was tested using a disc
      diffusion method; all isolates were resistant to cephalothin, aminoglycosides and
      beta-lactams, and sensitive only to some fluoroquinolones and tetracyclines.
      Histological examination revealed that A. lwoffii infection could cause
      pathological lesions in multiple organs and tissues, especially in liver, kidney,
      spleen and heart. These lesions included extensive haemorrhage, vacuolar
      degeneration, necrosis and inflammatory cell infiltration. To our knowledge, this
      is the first report on A. lwoffii as a virulent pathogen for fish of the
      Schizothorax genus.

PMID- 30239150
TI  - An On-Chip Method for Long-Term Growth and Real-Time Imaging of Brain Organoids.
AB  - Brain organoids are an emerging technique for studying human neurodevelopment in
      vitro, with biomedical implications. However, three-dimensional tissue culture
      poses several challenges, including lack of nutrient exchange at the organoid
      core and limited imaging accessibility of whole organoids. Here we present a
      method for culturing organoids in a micro-fabricated device that enables in situ
      real-time imaging over weeks with efficient nutrient exchange by diffusion. Our
      on-chip approach offers a means for studying the dynamics of organoid
      development, cell differentiation, cell cycle, and motion. (c) 2018 by John Wiley
      & Sons, Inc.

PMID- 30239151
TI  - Recent improvements in sports drug testing concerning the initial testing for
      peptidic drugs (< 2 kDa) - sample preparation, mass spectrometric detection, and
      data review.
AB  - In this work, a novel initial testing assay based on liquid chromatography-mass
      spectrometry is presented, enabling the detection of peptidic drugs and drug
      candidates (< 2 kDa) prohibited in sports. The assay covers representatives and
      metabolites of gonadotropin releasing hormone and its analogs (GnRHs), growth
      hormone secretagogues (GHS), growth hormone releasing peptides (GHRPs), and the
      Vasopressin-analog Desmopressin. The general objective of this work was to reduce
      sample preparation efforts to a minimum while preserving highest possible
      sensitivity and specificity of the assay, demonstrating limits of detection
      between 50 and 200 pg/mL. Here, a "dilute-and-inject" strategy provides the
      simplest conceivable sample preparation procedure. Furthermore, the combination
      of well-established strategies for the determination of peptides, such as two
      dimensional liquid chromatography, dimethyl sulfoxide (DMSO)-assisted
      electrospray ionization, high resolution mass spectrometric detection and a
      tailored reporter template, which facilitates data review enormously, provides a
      high-throughput initial testing assay for lower molecular mass peptidic and
      peptide-related analytes.

PMID- 30239152
TI  - Applicability and Clinical Validity of Nursing Outcomes Classification in a
      Nursing Intervention of Nutritional Counseling for Patients With Malnutrition.
AB  - PURPOSE: To determine the applicability of the Nursing Outcomes Classification
      (NOC) after nutritional counseling intervention in malnourished patients.
      METHODS: Prospective, randomized, open-label study in 106 hospital patients with
      malnutrition. The NOC indicators evaluated were 162202 and 180201. FINDINGS: The
      intervention group significantly increased both NOC indicator scores compared
      with the control group, these indicators significantly correlated with body mass
      index, Malnutrition Universal Screening Tool, and Barthel's Index. CONCLUSION:
      The NOC indicators are sensitive to patients' changes in clinical practice, and
      correlate well with other indicators in this context. IMPLICATIONS FOR NURSING
      PRACTICE: The NOC can be used to assess malnourished patients in the clinical
      setting.

PMID- 30239153
TI  - Whole Genome Next-Generation Sequencing Mutation Identification in Pseudomonas
      aeruginosa.
AB  - Identification of spontaneous or chemically induced bacterial mutations is a
      powerful tool for investigation of molecular mechanisms, including the mechanism
      of action of novel antibiotics. However, a major bottleneck to this approach has
      been the identification of the causative mutation underlying a phenotype of
      interest. Until recently, this has required time-consuming genetic analysis.
      However, the advent of relatively inexpensive and rapid next-generation
      sequencing (NGS) technologies has revolutionized the correlation of bacterial
      phenotypes and genotypes. In this article we describe a simple bioinformatics
      pipeline to identify differences between sequenced bacterial genomes. We also
      describe the procedures involved in growing, extracting, and purifying DNA, and
      preparation of sequencing libraries for one bacterial species, Pseudomonas
      aeruginosa. Similar protocols will be applicable to other bacterial species. (c)
      2018 by John Wiley & Sons, Inc.

PMID- 30239154
TI  - Assessment of the influence of viscoelasticity of cornea in animal ex vivo model
      using air-puff optical coherence tomography and corneal hysteresis.
AB  - Application of the air-puff swept source optical coherence tomography (SS-OCT)
      instrument to determine the influence of viscoelasticity on the relation between
      overall the air-puff force and corneal apex displacement of porcine corneas ex
      vivo is demonstrated. Simultaneous recording of time-evolution of the tissue
      displacement and air pulse stimulus allows obtaining valuable information related
      in part to the mechanical properties of the cornea. A novel approach based on
      quantitative analysis of the corneal hysteresis of OCT data is presented. The
      corneal response to the air pulse is assessed for different well-controlled
      intraocular pressure (IOP) levels and for the progression of cross-linking
      induced stiffness of the cornea. Micrometer resolution, fast acquisition and
      noncontact character of the air-puff SS-OCT measurements have potential to
      improve the in vivo assessment of mechanical properties of the human corneas.

PMID- 30239156
TI  - Effectiveness of curvilinear approach in dissection of Descemet's membrane: first
      500 cases - factors influencing graft preparation.
AB  - PURPOSE: To confirm the reproducibility of manual graft preparation using
      curvilinear forceps and evaluate the incidence and type of structural
      abnormalities of Descemet's membrane (DM) preventing successful grafts
      preparation. METHODS: Five hundred corneo-scleral buttons were prepared. Factors
      such as endothelial cell number before preparation, donor age, post-mortem time,
      time in culture, pigmentation of the trabecular meshwork and preparation
      characteristics of the fellow eye were analysed. According to the preparation
      characteristics, three groups were formed: A, uncomplicated; B, complicated
      preparation with stripping from the contralateral side; and C, failure of
      preparation. Three failed grafts were examined by transmission electron
      microscopy (TEM). RESULTS: Using curvilinear forceps, manual separation of DM was
      achieved without any adverse effects in 457 of 500 corneas (91.4%). In 32 corneas
      (6.4%) with micro-tears during preparation, stripping from the opposite side was
      possible. However, 11 of the 500 corneas (2.2%) showed extremely strong adhesion
      leading to multiple tears of DM and preventing successful preparation of the
      graft. Endothelial cell number, donor age, post-mortem time, time in culture and
      pigmentation of the trabecular meshwork showed no significant correlation with
      failure to successfully obtain a DM graft. Complicated graft preparations of one
      eye showed a highly significant correlation with complicated graft preparations
      in the fellow eye. TEM analysis of failed grafts showed abnormal invasion of
      stromal parts into the DM, cell accumulation and pigmentation in the DM plane.
      CONCLUSION: Using curvilinear forceps for dissecting of the graft shows valid and
      reproducible results in the vast majority (97.8%) of donor corneas.

PMID- 30239157
TI  - Detection of a novel HLA-B*46:01 variant, HLA-B*46:01:19, in a Taiwanese
      individual.
AB  - One nucleotide replacement at residue 369 of HLA-B*46:01:01 results in a new
      allele, HLA-B*46:01:19.

PMID- 30239155
TI  - Efficacy of exogenous pyruvate in TremblerJ mouse model of Charcot-Marie-Tooth
      neuropathy.
AB  - INTRODUCTION: Classic Charcot-Marie-Tooth (CMT) neuropathies including those with
      Schwann cell genetic defects exhibit a length-dependent process affecting the
      distal axon. Energy deprivation in the distal axon has been the proposed
      mechanism accounting for length-dependent distal axonal degeneration. We
      hypothesized that pyruvate, an intermediate glycolytic product, could restore
      nerve function, supplying lost energy to the distal axon. METHODS: To test this
      possibility, we supplied pyruvate to the drinking water of the Trembler-J (TrJ )
      mouse and assessed efficacy based on histology, electrophysiology, and functional
      outcomes. Pyruvate outcomes were compared with untreated TrJ controls alone or
      adeno-associated virus mediated NT-3 gene therapy (AAV1.NT-3)/pyruvate
      combinatorial approach. RESULTS: Pyruvate supplementation resulted increased
      myelinated fiber (MF) densities and myelin thickness in sciatic nerves. Combining
      pyruvate with proven efficacy from AAV1.tMCK.NT-3 gene therapy provided
      additional benefits showing improved compound muscle action potential amplitudes
      and nerve conduction velocities compared to pyruvate alone cohort. The end point
      motor performance of both the pyruvate and the combinatorial therapy cohorts was
      better than untreated TrJ controls. In a unilateral sciatic nerve crush paradigm,
      pyruvate supplementation improved myelin-based outcomes in both regenerating and
      the contralateral uncrushed nerves. CONCLUSIONS: This proof of principle study
      demonstrates that exogenous pyruvate alone or as adjunct therapy in TrJ may have
      clinical implications and is a candidate therapy for CMT neuropathies without
      known treatment.

PMID- 30239159
TI  - Identification of the novel HLA-DPA1*02:01:01:06 allele in a Saudi individual.
AB  - HLA-DPA1*02:01:01:06 differs from HLA-DPA1*02:01:01:01 by a single nucleotide
      substitution (T -> G) at position 948.

PMID- 30239160
TI  - Adverse effects of amiodarone therapy in adults with congenital heart disease.
AB  - OBJECTIVE: Amiodarone is a highly effective antiarrhythmic therapy, however its
      toxicity profile often limits treatment. This is particularly relevant in adults
      with congenital heart disease (CHD), who are often young and in whom other
      antiarrhythmic agents commonly fail or are contraindicated. We sought to
      determine incidence and predictors of adverse effects caused by amiodarone in
      adult CHD (ACHD). DESIGN: A retrospective review of patients with moderate to
      complex ACHD treated with amiodarone at our center between 2000 and 2017 was
      performed. Incidence and predictors of adverse effects were described. Efficacy
      of amiodarone therapy in controlling the clinical arrhythmia was assessed as
      complete, partial, or failed. RESULTS: Amiodarone was prescribed in 57 patients
      of 902 ACHD patients reviewed (6%), for a mean duration of 2.7 +/- 4.3 years.
      Significant adverse effects occurred in 56%, most commonly thyroid dysfunction,
      with amiodarone-induced thyrotoxicosis (AIT) in 30% and amiodarone-induced
      hypothyroidism in 14%. AIT frequently led to arrhythmia exacerbation and occurred
      most in those with Fontan anatomy. Severe dermatological effects were seen in 7%
      and bradycardia requiring pacing in 5%. Interstitial lung disease, peripheral
      neuropathy and alopecia were observed in single cases. Amiodarone toxicity led to
      discontinuation of the drug in 42%. Amiodarone was highly effective when
      tolerated, however, achieving complete arrhythmia control in 63%, partial control
      in 35%, with failure to control in only one patient. CONCLUSIONS: Amiodarone
      therapy is effective in moderate to complex ACHD patients, but is frequently
      limited by adverse effects. ACHD patients seem especially vulnerable to thyroid
      dysfunction, with Fontan patients in particular at increased risk of AIT.

PMID- 30239158
TI  - Impaired white matter integrity between premotor cortex and basal ganglia in
      writer's cramp.
AB  - INTRODUCTION: Writer's cramp (WC) as a focal hand dystonia is characterized by
      abnormal postures of the hand during writing. Impaired inhibition and maladaptive
      plasticity in circuits linking the basal ganglia and sensorimotor cortices have
      been described. In particular, a dysfunction of lateral premotor cortices has
      been associated with impaired motor control in WC. We applied diffusion tensor
      imaging to identify changes in white matter connectivity between premotor regions
      and important cortical and subcortical structures. METHODS: Whole brain white
      matter tracts were reconstructed in 18 right-handed WC patients and 18 matched
      controls, using probabilistic fiber tracking. We restricted our analyses to left
      hemispheric fibers between the middle frontal gyrus (MFG) and basal ganglia,
      thalamus, primary motor, and sensory cortex. Diffusion parameters (fractional
      anisotropy and linear anisotropy) were compared between both groups. RESULTS: A
      significant reduction in fractional anisotropy values was shown for patients
      (mean +/- SD: 0.37 +/- 0.02) vs. controls (0.39 +/- 0.03) regarding fibers
      between the left-sided MFG and the putamen (p < 0.05). The same applied for
      linear anisotropy values in this connection (p < 0.05). CONCLUSIONS: Our results
      suggest an impaired structural connectivity between the left-hemispheric MFG and
      putamen with a loss of equally aligned fibers in WC patients. This could reflect
      a structural basis for functional findings interpreted as altered inhibition and
      plasticity, both within the premotor cortex and the basal ganglia, that at last
      lead to the clinical symptoms of WC.

PMID- 30239161
TI  - Photolithographically Patterned Hydrogels with Programmed Deformations.
AB  - Programmed deformations are widespread in nature, providing elegant paradigms to
      design self-morphing materials with promising applications in biomedical devices,
      flexible electronics, soft robotics, etc. In this emerging field, hydrogels are
      an ideal material to investigate the deformation principle and the structure
      deformation relationship. One crucial step is to construct heterogeneous
      structures in a facile yet effective way. Herein, we provide a focus review on
      different deformation modes and corresponding structural features of hydrogels.
      Photolithography is a versatile approach to control the outer shape of the
      hydrogel and spatial distribution of the component in the hydrogel, endowing the
      patterned hydrogels with programmed internal stress and thus controllable
      deformations. Specifically, cooperative deformations take place in periodically
      patterned hydrogels with in-plane gradients, and multiple morphing structures are
      formed in one patterned hydrogel using selective preswelling to direct the
      buckling of each unit. The structural control strategy and deformation principles
      should be applicable to other materials with broad applications in diverse areas.

PMID- 30239163
TI  - The prevalent Boxer MHC class Ia allotype dog leukocyte antigen (DLA)-88*034:01
      preferentially binds nonamer peptides with a defined motif.
AB  - Development of effective immunotherapy for chemoresistant malignancies can be
      advanced by studies in spontaneous cancer models, such as the dog. A crucial
      first step, T-cell epitope discovery, can be assisted by determination of binding
      motifs of common dog leukocyte antigen (DLA) class Ia allotypes. Boxers are
      popular, inbred dogs with increased risks of relevant target cancers and
      restricted MHC diversity. We sought to identify the motif of DLA-88*034:01, a
      breed-dominant allotype, to assist peptide prediction from tumor antigens. Mass
      spectrometry of eluted peptides showed a preference for nonamers with conserved
      amino acid preferences: basic at position (P)1; hydrophobic at P2; acidic at P4;
      histidine at P6; and phenylalanine at P9. This data should expedite finding
      epitopes restricted by this DLA-88 allotype.

PMID- 30239164
TI  - Refractive index and pulse broadening characterization using oil immersion and
      its influence on three-photon microscopy excited at the 1700-nm window.
AB  - Three-photon microscopy excited at the 1700-nm window enables deep-tissue
      penetration. However, the refractive indices of commonly used immersion oils, and
      the resultant pulse broadening are not known, preventing imaging optimization.
      Here, we demonstrate detailed characterization of the refractive index, pulse
      broadening and distortion for excitation pulses at this window for commonly used
      immersion oils. On the physical side, we uncover that absorption, rather than
      material dispersion, is the main cause of pulse broadening and distortion. On the
      application side, comparative three-photon imaging results indicate that 1600-nm
      excitation yields 5 times higher three-photon signal than 1690-nm excitation.

PMID- 30239162
TI  - Radiotherapy improves the survival of patients with stage IV NSCLC: A propensity
      score matched analysis of the SEER database.
AB  - OBJECTIVES: The survival advantage of radiotherapy (RT) for patients with stage
      IV non-small cell lung cancer (NSCLC) has not been adequately evaluated. METHODS:
      We analyzed stage IV NSCLC patients enrolled from the Surveillance, Epidemiology,
      and End Results (SEER) registry through January 2010 to December 2012. Propensity
      score (PS) analysis with 1:1 nearest neighbor matching method was used to ensure
      well-balanced characteristics of all comparison groups by histological types and
      metastatic sites. Kaplan-Meier and Cox proportional hazardous model were used to
      evaluate the overall survival (OS), cancer-specific survival (CSS), and
      corresponding 95% confidence interval (95%CI). RESULTS: Generally speaking, there
      was a trend toward improved OS and CSS for using RT to stage IV NSCLC patients
      for any metastatic sites and for any histological types except adenocarcinoma
      (AD). Radiotherapy significantly improved the survival of NSCLC patients with
      metastasis to brain (P < 0.001), especially for AD (P < 0.001). For stage IV lung
      cancer patients with squamous cell carcinoma (SQC), RT for any metastatic sites
      could universally improve the OS (P < 0.001) and CSS (P < 0.001). In particular,
      RT was also associated with improving OS (P < 0.001) and CSS (P = 0.012) for
      stage IV patients with metastases of two or more sites, ie, polymetastatic
      disease. Furthermore, for those stage IV SQC patients without metastasis, RT,
      most likely to the primary site, also significantly improved the survival (P <
      0.001). CONCLUSIONS: The results support that RT might improve the survival of
      patients with metastatic NSCLC in a PS-matched patient cohort from the large SEER
      database. It is prudent to carefully select patients for RT in metastatic NSCLC.

PMID- 30239165
TI  - Food or money? Children's brains respond differently to rewards regardless of
      weight status.
AB  - BACKGROUND: Brain responses to both food and monetary rewards have been linked to
      weight gain and obesity in adults, suggesting that general sensitivity to reward
      contributes to overeating. However, the relationship between brain reward
      response and body weight in children is unclear. OBJECTIVE: The objective of this
      study was to assess the brain's response to multiple rewards and the relationship
      to body weight in children. METHODS: We tested this by performing functional
      magnetic resonance imaging while children (7- to 11-years-old; healthy weight [n
      = 31], overweight/obese [n = 30]) played a modified card-guessing task to assess
      blood-oxygen-level-dependent (BOLD) response to anticipating and winning food and
      money rewards. Functional magnetic resonance imaging data were analysed using a
      region of interest and exploratory whole-brain approach. RESULTS: Region of
      interest results demonstrated increased BOLD response in the striatum to
      anticipating food vs. neutral (control) and winning money vs. neutral. Whole
      brain data showed that winning money vs. food was associated with increased
      activation in the striatum, as well as regions associated with cognitive control
      and emotion. Notably, for both approaches, these effects were independent of
      child weight status. Additionally, children's reported food responsiveness and
      emotional overeating were negatively correlated with the BOLD response in the
      left cingulate gyrus for winning food vs. money. CONCLUSION: Overall, findings
      from this study show that regions associated with reward, cognitive control and
      emotion may play a role in the brain's response to food and money rewards,
      independently of how much the child weighs. These findings provide insight into
      reward sensitivity in children, which may have implications for understanding
      overeating and the development of obesity.

PMID- 30239166
TI  - Strong in combination: Polyphasic approach enhances arguments for cold-assigned
      cyanobacterial endemism.
AB  - Cyanobacteria of biological soil crusts (BSCs) represent an important part of
      circumpolar and Alpine ecosystems, serve as indicators for ecological condition
      and climate change, and function as ecosystem engineers by soil stabilization or
      carbon and nitrogen input. The characterization of cyanobacteria from both polar
      regions remains extremely important to understand geographic distribution
      patterns and community compositions. This study is the first of its kind
      revealing the efficiency of combining denaturing gradient gel electrophoresis
      (DGGE), light microscopy and culture-based 16S rRNA gene sequencing, applied to
      polar and Alpine cyanobacteria dominated BSCs. This study aimed to show the
      living proportion of cyanobacteria as an extension to previously published meta
      transcriptome data of the same study sites. Molecular fingerprints showed a
      distinct clustering of cyanobacterial communities with a close relationship
      between Arctic and Alpine populations, which differed from those found in
      Antarctica. Species richness and diversity supported these results, which were
      also confirmed by microscopic investigations of living cyanobacteria from the
      BSCs. Isolate-based sequencing corroborated these trends as cold biome clades
      were assigned, which included a potentially new Arctic clade of Oculatella. Thus,
      our results contribute to the debate regarding biogeography of cyanobacteria of
      cold biomes.

PMID- 30239167
TI  - Clinical and genetic characteristics of abnormal glucose tolerance in Japanese
      women in the first year after gestational diabetes mellitus.
AB  - AIMS/INTRODUCTION: Risk factors of type 2 diabetes mellitus in Japanese women
      with recent gestational diabetes mellitus are unknown. The objective of the
      present study was to investigate the clinical and genetic characteristics
      associated with postpartum abnormal glucose tolerance in Japanese women with
      gestational diabetes mellitus. MATERIALS AND METHODS: A total of 213 Japanese
      women with recent gestational diabetes mellitus who underwent a postpartum 2-h
      oral glucose tolerance test were investigated. The association between antepartum
      clinical characteristics and postpartum abnormal glucose tolerance (diabetes or
      prediabetes based on the Japan Diabetes Society criteria) was examined.
      Frequencies of 45 known type 2 diabetes mellitus-associated genetic variants were
      also compared between women with and without postpartum abnormal glucose
      tolerance. RESULTS: A total of 59 women showed postpartum abnormal glucose
      tolerance (prediabetes, n = 51; diabetes, n = 8). Plasma glucose levels at 1 or 2
      h, the insulinogenic index and the insulin secretion-sensitivity index-2 of the
      antepartum oral glucose tolerance test were independent of postpartum abnormal
      glucose tolerance risk factors (P = 0.006, P = 0.00002, P = 0.01 and P = 0.006,
      respectively). Four genetic variants (rs266729 [ADIPOQ], rs6017317 [HNF4A],
      rs5215 [KCNJ11] and rs7177055 [HMG20A]) showed a nominally significant
      association with postpartum abnormal glucose tolerance (P < 0.05, respectively).
      Among these, three were related to insulin secretion. Postpartum abnormal glucose
      tolerance risk significantly increased with increasing risk-allele number (P =
      0.0005; odds ratio 1.91). CONCLUSIONS: Clinical features and genetic variants
      related to impaired insulin secretion are risk factors of postpartum abnormal
      glucose tolerance in Japanese women with recent gestational diabetes mellitus.

PMID- 30239169
TI  - Effects of temperature on bacterial microbiome composition in Ixodes scapularis
      ticks.
AB  - Ixodes scapularis, the blacklegged deer tick, is the principal vector of Lyme
      disease in North America. Environmental factors are known to influence regional
      and seasonal incidence of Lyme disease and possibly the endemicity of the disease
      to the northeastern and upper mid-western regions of the United States. With a
      goal to understand the impact of environmental temperature on microbial
      communities within the tick, we investigated the bacterial microbiome of colony
      reared I. scapularis ticks statically incubated at different temperatures (4, 20,
      30, and 37 degrees C) at a constant humidity in a controlled laboratory setting
      by comparison of sequenced amplicons of the bacterial 16S V4 rRNA gene to that of
      the untreated baseline controls. The microbiomes of colony-reared I. scapularis
      males were distinct than that of females, which were entirely dominated by
      Rickettsia. In silico removal of Rickettsia sequences from female data revealed
      the underlying bacterial community, which is consistent in complexity with those
      seen among male ticks. The bacterial community composition of these ticks changes
      upon incubation at 30 degrees C for a week and 37 degrees C for more than 5 days.
      Moreover, the male ticks incubated at 30 and 37 degrees C exhibited significantly
      different bacterial diversity compared to the initial baseline microbiome, and
      the change in bacterial diversity was dependent upon duration of exposure.
      Rickettsia-free data revealed a significantly different bacterial diversity in
      female ticks incubated at 37 degrees C compared to that of 4 and 20 degrees C
      treatments. These results provide experimental evidence that environmental
      temperature can impact the tick bacterial microbiome in a laboratory setting.

PMID- 30239168
TI  - Adenocarcinoma of the esophagogastric junction and its background mucosal
      pathology: A comparative analysis according to Siewert classification in a
      Japanese cohort.
AB  - Adenocarcinoma of the esophagogastric junction (AEG) has heterogeneous
      carcinogenic process due to its location straddling the esophagogastric junction.
      We assessed background mucosal pathology and its correlation with
      clinicopathological features of each Siewert type of AEG. Clinicopathological and
      immunohistochemical analyses of 103 AEGs and 58 gastric cancers (GCs) were
      conducted. Background mucosal features were evaluated according to the updated
      Sydney System. Siewert classification divided 103 AEGs into three type I, 75 type
      II, and 25 type III tumors, respectively. Two type I, 9 type II AEGs, and none of
      type III AEGs were Barrett-related and were excluded from further analysis.
      Background mucosa of type III AEGs more frequently showed moderate to marked
      degree of atrophy and intestinal metaplasia than those of type II AEGs and was
      very similar to those of GCs. Among type II AEGs, tumors with atrophic background
      were significantly associated with higher patient age and intestinal-type
      histology. Type II AEGs with nonatrophic background, but not those with atrophic
      background, showed more frequent mismatch repair deficiency, TP53 overexpression,
      and less frequent intestinal phenotypic markers expression than type III AEG or
      GC. Type II AEGs with atrophic background involved suprapancreatic nodes more
      frequently than those without. We demonstrated that chronic atrophic gastritis
      was a major precancerous condition of AEG in the Japanese population, especially
      Siewert type III which had background mucosal pathology similar to that of GC.
      Type II AEGs with and without atrophic background showed some clinicopathological
      differences, and these observations might represent heterogeneous carcinogenic
      process within type II AEGs.

PMID- 30239170
TI  - Pathological significance of urinary complement activation in diabetic
      nephropathy: A full view from the development of the disease.
AB  - AIMS/INTRODUCTION: The aim of the present study was to obtain a full view of the
      changes of urinary complement activation products in the development of diabetic
      nephropathy and explore their possible significance in the disease process.
      MATERIALS AND METHODS: A total of 62 patients at different stages of diabetic
      nephropathy, 20 diabetes patients without nephropathy and 20 healthy persons were
      enrolled. Urinary complement activation products, including C3a, C5a and C5b-9,
      were measured, and their associations with the progression of the disease were
      analyzed. RESULTS: The urinary complement activation products increased markedly
      since the proteinuria stage, and were parallel with the progression of diabetic
      nephropathy. More severe renal tubular damage was observed in patients with
      higher levels of urinary complement activation products. The urinary complement
      activation products levels correlated closely with renal tubulointerstitial
      injury score and relative tubular interstitial volume. Multivariate regression
      analysis showed that elevated urinary complement activation products were
      independent risk factors for tubular injury in diabetic nephropathy patients.
      CONCLUSIONS: Urinary complement activation might have a role in renal tubular
      interstitial injury in patients with diabetic nephropathy, especially in patients
      at a later stage of the disease.

PMID- 30239171
TI  - Accurate and Rapid Protein Concentration Measurement of In-Process, High
      Concentration Protein Pools.
AB  - Protein concentration is a critical product quality attribute and required for
      any therapeutic protein. Many commercial and investigational new biologics are
      now formulated at high concentrations (>100 mg/ml) to achieve successful
      subcutaneous administration. Assaying protein concentration in high concentration
      formulations poses a challenge, as traditional absorption spectroscopy and
      UPLC/HPLC (ultra/high performance liquid chromatography) assays cannot accurately
      measure such high concentrations without further solution manipulation. However,
      recent advances in UV/vis technology have led to the creation of instruments that
      measure samples at relatively short (<1 cm) path lengths, which would allow them
      to accurately measure high concentration protein samples in accordance with Beer
      Lambert Law principles. In this research, samples of five different proteins at
      concentrations ranging from 0.15 to 242 mg/ml (corresponding to OD280 vales of
      0.15-315 AU) were measured on two different instruments employing different
      techniques of low path length UV/vis measurements. In order for the techniques to
      meet MSD's acceptance criteria for release assays, measurements were required to
      be accurate to within 10% of a reference measurement (performed on a traditional
      UV/vis spectrophotometer) and to be precise within 5% CV. The results show that
      using a technique known as slope spectroscopy, it is possible to measure OD280
      from 0.5 to 315 AU with <7% error relative to the reference measurement. If
      instead measurements are taken using an instrument utilizing a single, small path
      length, it is possible to measure absorbances from 0.2 to ~75 AU with <7% error.
      This article concludes that the slope spectroscopy technique performed within the
      acceptance criteria across the full range of measured absorbances and that the
      single, short path length measurement performed within the acceptance criteria up
      to 75 AU.

PMID- 30239172
TI  - Tanshinone sensitized the antitumor effects of irradiation on laryngeal cancer
      via JNK pathway.
AB  - Laryngeal cancer is a common cancer occurred in the head and neck. Irradiation
      sensitivity is a problem affecting the treatment of laryngeal cancer. Tanshinone
      IIA has been reported to play an important role in treating multiple diseases;
      yet, whether Tanshinone IIA can be an irradiation sensitizer has not been
      reported. Clonogenic assay, annexin-V/propidium iodide double-staining assay, and
      Cell Counting Kit-8 assay were performed to detect cell survival, proliferation,
      apoptosis, and viability. Mouse laryngeal cancer xenograft model was established
      and subjected to tumor size analysis. Tanshinone IIA treatment increased the
      irradiation sensitivity of laryngeal cancer cells by reducing cell survival,
      viability and proliferation, and increasing cell apoptosis. Tanshinone IIA
      treatment increased the survival period of mice in the in vivo laryngeal cancer
      model, evidenced by decreased growth and weight of tumors, which was possibly
      mediated through the JNK pathway. Tanshinone IIA increases the sensitivity to
      irradiation in laryngeal cancer cells and in vivo laryngeal cancer model,
      suggesting that Tanshinone IIA can be a therapeutic antitumor agent for treating
      laryngeal cancer.

PMID- 30239173
TI  - Tissue biomechanics during cranial neural tube closure measured by Brillouin
      microscopy and optical coherence tomography.
AB  - BACKGROUND: Embryonic development involves the interplay of driving forces that
      shape the tissue and the mechanical resistance that the tissue offers in
      response. While increasing evidence has suggested the crucial role of physical
      mechanisms underlying embryo development, tissue biomechanics is not well
      understood because of the lack of techniques that can quantify the stiffness of
      tissue in situ with 3D high-resolution and in a noncontact manner. METHODS: We
      used two all-optical techniques, optical coherence tomography (OCT) and Brillouin
      microscopy, to map the longitudinal modulus of the tissue from mouse embryos in
      situ. RESULTS: We acquired 2D mechanical maps of the neural tube region of
      embryos at embryonic day (E) 8.5 (n = 2) and E9.5 (n = 2) with submicron spatial
      resolution. We found the modulus of tissue varied distinctly within the neural
      tube region of the same embryo and between embryos at different development
      stages, suggesting our technique has enough sensitivity and spatial resolution to
      monitor the tissue mechanics during embryonic development in a noncontact and
      noninvasive manner. CONCLUSIONS: We demonstrated the capability of OCT-guided
      Brillouin microscopy to quantify tissue longitudinal modulus of mouse embryos in
      situ, and observed distinct change in the modulus during the closure of cranial
      neural tube. Although this preliminary work cannot provide definitive conclusions
      on biomechanics of neural tube closure yet as a result of the limited number of
      samples, it provides an approach of quantifying the tissue mechanics during
      embryo development in situ, thus could be helpful in investigating the role of
      tissue biomechanics in the regulation of embryonic development. Our next study
      involving more embryo samples will investigate systematic changes in tissue
      mechanics during embryonic development.

PMID- 30239175
TI  - Population-based priors in cardiac model personalisation for consistent parameter
      estimation in heterogeneous databases.
AB  - Personalised cardiac models are a virtual representation of the patient heart,
      with parameter values for which the simulation fits the available clinical
      measurements. Models usually have a large number of parameters while the
      available data for a given patient are typically limited to a small set of
      measurements; thus, the parameters cannot be estimated uniquely. This is a
      practical obstacle for clinical applications, where accurate parameter values can
      be important. Here, we explore an original approach based on an algorithm called
      Iteratively Updated Priors (IUP), in which we perform successive personalisations
      of a full database through maximum a posteriori (MAP) estimation, where the prior
      probability at an iteration is set from the distribution of personalised
      parameters in the database at the previous iteration. At the convergence of the
      algorithm, estimated parameters of the population lie on a linear subspace of
      reduced (and possibly sufficient) dimension in which for each case of the
      database, there is a (possibly unique) parameter value for which the simulation
      fits the measurements. We first show how this property can help the modeller
      select a relevant parameter subspace for personalisation. In addition, since the
      resulting priors in this subspace represent the population statistics in this
      subspace, they can be used to perform consistent parameter estimation for cases
      where measurements are possibly different or missing in the database, which we
      illustrate with the personalisation of a heterogeneous database of 811 cases.

PMID- 30239174
TI  - Identification of tRNA-derived small noncoding RNAs as potential biomarkers for
      prediction of recurrence in triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC), an intrinsic subtype of breast cancer, is
      characterized by aggressive pathology and shorter overall survival. Yet there is
      no effective therapy for these patients. Breast cancer stem cells (BCSCs) in TNBC
      may account for treatment failure. It is urgent to identify new therapeutic
      targets for TNBC. tRNA-derived small noncoding RNAs (tDRs) represent a new class
      of small noncoding RNAs (sncRNA), which have been reported in some human diseases
      and biological processes. However, there is no detailed information about the
      relationship between tDRs and BCSCs. In this study, a population of CD44+ /CD24
      /low cells was isolated and identified by reliable BCSC surface markers. tDR
      expression profiles in TNBC and non-TNBC CSCs were performed by RNA sequencing. A
      total of 1327 differentially expressed tDRs contained 18 upregulated and 54
      downregulated in TNBC group. Furthermore, the selected tDRs were validated by
      quantitative reverse transcription-polymerase chain reaction (qRT-PCR). tDR
      000620 expression level was consistently lower in TNBC cell lines CSCs (all P <
      0.05) and serum samples (t = 2.597, P = 0.013). tDR-000620 expression was
      significant association with age (P = 0.018), node status (P = 0.026) and local
      recurrence (P = 0.019) by chi-square test. Kaplan-Meier method with log-rank test
      for comparison of recurrence curves. The results showed that the tDR-000620
      expression (P = 0.002) and node status (P = 0.001) group were statistically
      significant with recurrence-free survival. Furthermore, multivariate Cox
      regression demonstrated that lymphatic metastasis (HR, 3.616; 95% CI, 1.234
      10.596; P = 0.019) and low tDR-000620 expression (HR, 0.265; 95% CI, 0.073-0.959;
      P = 0.043) were two independent adverse predictive factors for recurrence-free
      survival. Finally, we found that tDR-000620 participated in some important
      biological processes though GO and KEGG analysis. Taken together, our study
      reveals the expression profiles of tDRs in TNBC and non-TNBC CSCs. It offers
      helpful information to understand the tDR-000620 expression is responsible for
      the aggressive phenotype of BCSCs. It may provide predictive biomarkers and
      therapeutic targets for TNBC recurrence.

PMID- 30239177
TI  - Effects of ambulatory emergency care on organisational and patient outcomes.
AB  - The aim of ambulatory emergency care (AEC) is to provide patients with ambulatory
      care-sensitive conditions with safe and appropriate emergency care on the day
      they attend hospital. It is achieved without admitting patients to a hospital bed
      and is therefore an admissions-avoidance service. Gloucestershire Hospitals NHS
      Foundation Trust has been running AEC at its two acute sites since May 2014. This
      article reports findings from a service review that looked at whether there were
      improvements in health outcomes for patients accessing AEC compared with those
      for patients who had presented to emergency care before the service was set up.
      The article describes how a review of patient notes found that patients managed
      through AEC had fewer diagnostic procedures performed and were more likely to be
      discharged to their normal place of residence.

PMID- 30239176
TI  - Are people with amyotrophic lateral sclerosis (ALS) particularly nice? An
      international online case-control study of the Big Five personality factors.
AB  - BACKGROUND: Many people with ALS have been suggested to have a "nice"
      personality, but most ALS personality studies to date have had limited numbers of
      participants and have not taken into account personality differences between
      genders. We used Big Five Inventory data obtained from an online questionnaire
      looking for risk factors for ALS to investigate personality traits in large
      numbers of people with ALS and controls. METHODS: A total of 741 questionnaire
      respondents aged 40 years and over indicated the extent to which they agreed with
      each of the 44 Big Five Inventory statements. Respondents were 339 with ALS (212
      male, 127 female) who responded to the statements as they applied to them before
      their diagnosis and 402 controls (120 male, 282 female). Unpaired t tests with
      95% confidence intervals were used to compare mean values of Big Five-factor
      scores. RESULTS: Female respondents taken together had higher mean scores for
      Agreeableness and Neuroticism than all male respondents. Male ALS respondents had
      higher mean scores than male controls for Conscientiousness and Extraversion.
      Female ALS respondents had higher mean scores than female controls for
      Agreeableness, Conscientiousness, and Extraversion, and a lower score for
      Neuroticism. CONCLUSIONS: Many people with ALS have personality traits that are
      likely to underlie the perception they are particularly "nice." This raises the
      possibility that genetic polymorphisms that influence personality could play a
      role in ALS. Furthermore, different personality traits could underlie lifestyle
      choices that are currently thought to be risk factors for ALS.

PMID- 30239178
TI  - [Original conception of polymerized diagnostic wax-up in an occlusal
      rehabilitation of distal unilateral edentulous by combined prosthesis].
AB  - Rehabilitation by combined prosthesis is a therapy that requires a methodical
      approach especially in the case of large unilateral edentulous when all occlusal
      parameters are to be restored. The recording of the maxilla-mandibular position
      is requested at various stages of the treatment. In this context, the use of
      polymerized diagnostic wax up, is an evident tool for accurately recording and
      transfer of all occlusal data previously validated, yet concerning the global
      rehabilitation of unilateral distal edentulous, its stability and exact re
      positioning at various prosthetic sequences remain uncertain.The aim of this
      study was to develop an original conception of the polymerized diagnostic wax up
      that will allow us to benefit from all its advantages in complex rehabilitation
      of edentulous unilateral of large extent.

PMID- 30239179
TI  - Natural, polarized light and the choice of composite: a key to success in shade
      matching of direct anterior restorations- Part I.
AB  - The biggest challenge while restoring anterior teeth is shade matching. Hue,
      chroma, value, opacity, translucency, intensity and anatomy must be seen to be
      reproduced. To see we need light, knowing that there is a strong relation between
      the nature of light and the components of natural teeth. This article enlightens
      the way to do the shade matching and the stratification of anterior teeth by
      choosing the relevant materials to mimic the nature.The physical properties of
      natural and polarized light will be studied to understand their correlation with
      dental materials and natural teeth to use them in the best combination.

PMID- 30239180
TI  - [Mandibular osteitis on a periapical granuloma mimicking an osteosarcoma: a case
      report].
AB  - Introduction: Osteitis is an inflammatory disease of bone tissue. Its clinical
      presentation varies according to the site, presence or absence of pus, duration
      and etiology. It represents one of the endo-periodontal diseases complication. We
      report the case of a mandibular osteitis having led to confusion with an
      ostesarcoma. Observation: A 13-year-old boy was referred to our department for a
      right low swelling with suspicion of mandible osteosarcoma. The lesion's
      evolution was 6 weeks. With the local aggressiveness and the speed evolution, the
      first diagnosis proposed was a mandibular osteosarcoma. Based on the clinical and
      radiological data established, the diagnosis of mandibular osteitis on a
      periapical granuloma was made and the treatment consisted on the causal tooth
      extraction with curettage of the periapical lesion associated to the prescription
      of macrolide (ERY(r)). The clinical follow-up was 6 weeks, a recovery with
      cessation of clinical signs were noticed. Discussion: The differential diagnosis
      facing the clinical context is an osteitis on a periapical inflammatory cyst and
      especially mandibular osteosarcoma. For the therapy, it's a 3 components
      treatment (etiology, medical and surgical) to obtain a recovery.

PMID- 30239181
TI  - [Keratocystic odontogenic tumor: a case report].
AB  - First described by Philipsen in 1956, the odontogenic keratocyst is characterized
      by a large squamous keratinization of its border, an aggressive growth and a high
      recurrent rate. It is now designated by the World Health Organization as a
      Keratocystic Odontogenic Tumor (KOT). Clinically, the KOT is manifested by an
      asymptomatic growth. Radiographically, it appears as a well-defined unilocular or
      multilocular osteolytic lesion. The diagnostic approach is based on a combined
      analysis of the medical history, the clinical appearance and the radiographic
      appearance. The diagnosis may be confirmed by the anatomical pathology report.
      Finally, treatment consists of surgical excision and follow up is characterized
      by a high rate of recurrence. The authors report a case of keratocystic
      odontogenic tumor of the mandible and review the various diagnoses, therapeutics
      and follow up aspects of this type of tumors.

PMID- 30239182
TI  - Perceptions, expectations, and reactions of caregivers to cleft lip and palate
      repair in a tertiary hospital.
AB  - Background: Cleft lip and/or palate (CL/P) deformities are the most common
      congenital abnormalities of the orofacial structures. Affected individuals
      experience major clinical, functional, aesthetic and psychosocial impacts.
      Objectives: The aim of our study was to identify the perceptions, expectations
      and reactions of parents and caregivers to cleft lip and palate surgery.
      Materials and methods: Interviewer administered questionnaires were used to
      collect data from parents/caregivers of patients with cleft lip and/or palate
      operated on by the cleft team at University of Port Harcourt Teaching Hospital.
      Results: Only three (2.8%) of the caregivers indicated that they knew the cause
      of CLP which they attributed to drugs, infections and contraceptives taken while
      about half of them admitted that they avoided taking these children to certain
      places. The participants were very concerned about the speech 15 (41.7%) and
      feeding 9 (25.0%) of the children. Most wanted the surgery performed in order to
      improve appearance 25 (69.5%), speech 8 (22.2%) and feeding 2 (5.6%). More than
      half of the parents/caregivers 21 (58.3%) expected excellent results from the
      surgery whilst 1 (2.8%) expected poor results. Most believed the surgery would
      indeed make a great difference in speech 14 (38.9%) and appearance 11 (30.6%).
      Majority, 30 (83%) were happy with the immediate outcome of the surgery and with
      their hospital experience 13, (36.1%). Conclusions: This study revealed that most
      parents/caregivers of children with CLP believed this condition to be due to
      various factors and did not know the etiology. Expectations of the result of
      surgical repair of CLP surgery were high and their reactions were majorly
      positive.

PMID- 30239183
TI  - Spray Assembly of Metal-Phenolic Networks: Formation, Growth, and Applications.
AB  - Hybrid conformal coatings, such as metal-phenolic networks (MPNs) that are
      constructed from the coordination-driven assembly of natural phenolic ligands,
      are of interest in areas including biomedicine, separations, and energy. To date,
      most MPN coatings have been prepared by immersing substrates in solutions
      containing the phenolic ligands and metal ions, which is a suitable method for
      coating small or flexible objects. In contrast, more industrially relevant
      methods for coating and patterning large substrates, such as spray assembly, have
      been explored to a lesser extent toward the fabrication of MPNs, particularly
      regarding the effect of process variables on MPN growth. Herein, a spray assembly
      method was used to fabricate MPN coatings with various phenolic building blocks
      and metal ions and their formation and patterning were explored for different
      applications. Different process parameters including solvent, pH, and metal
      ligand pair allowed for control over the film properties such as thickness and
      roughness. On the basis of these investigations, a potential route for the
      formation of spray-assembled MPN films was proposed. Conditions favoring the
      formation of bis complexes could produce thicker coatings than those favoring the
      formation of mono or tris complexes. Finally, the spray-assembled MPNs were used
      to generate superhydrophilic membranes for oil-water separation and colorless
      films for UV shielding. The present study provides insights into the chemistry of
      MPN assembly and holds promise for advancing the fabrication of multifunctional
      hybrid materials.

PMID- 30239184
TI  - Advanced Electron Paramagnetic Resonance Studies of a Ternary Complex of Copper,
      Amyloid-beta, and a Chemical Regulator.
AB  - Although there has been extensive effort to develop chemical regulators, progress
      has been static, in part because of these regulators' unclear mechanisms. Here,
      we report using advanced electron paramagnetic resonance (EPR) spectroscopy to
      obtain the first molecular-level structural information regarding a ternary
      complex of CuII-amyloid-beta (Abeta) with a chemical regulator that can
      specifically modulate Cu-induced Abeta aggregation. Our advanced EPR
      spectroscopic results revealed that a chemical regulator (1) for CuII-Abeta1-16
      disrupted the coordination environment of CuII in Abeta, resulting in the
      detachment of the primary amine at the N-terminal and a carbonyl group between
      Asp1 and Ala2 from the CuII center and the subsequent formation of a ternary
      complex, chemical regulator-CuII-Abeta1-16. Therefore, our results demonstrate
      how a chemical regulator interacts with metal-Abeta at the molecular level. These
      findings provide novel insight into working mechanisms and thereby contribute to
      the establishment of a rational design for chemical regulators of metal-Abeta
      complexes.

PMID- 30239185
TI  - Durable Sodium Battery with a Flexible Na3Zr2Si2PO12-PVDF-HFP Composite
      Electrolyte and Sodium/Carbon Cloth Anode.
AB  - High-performance electrolytes and electrode materials play a critical role in
      advanced sodium-ion batteries with higher energy densities. In this work, we
      prepared a poly(methyl methacrylate)-filled composite electrolyte (named as GHSE)
      by in situ polymerization of methyl methacrylate in the porous Na3Zr2Si2PO12
      polymer vinylidene fluoride-hexafluoropropylene composite membrane for the first
      time. The GHSE membrane exhibits a high ionic conductivity (2.78 * 10-3 S cm-1),
      wide electrochemical window (~4.9 V), high Na+ ion transference number (~0.63),
      good thermal stability and flexibility, as well as smaller interfacial
      resistance. Moreover, a composite Na/C anode was prepared, which shows good
      dendrite suppression ability. The full cell Na0.67Ni0.23Mg0.1Mn0.67O2 |GHSE|Na/C
      exhibits excellent rate capability with an initial discharge capacity of 96 mAh g
      1 even at a higher current density of 192 mA g-1 and excellent cyclability for
      600 cycles. These results suggest that the GHSE and Na/C anode are promising
      electrolyte and anode materials for Na-ion batteries, respectively.

PMID- 30239186
TI  - Type II Kinase Inhibitors Targeting Cys-Gatekeeper Kinases Display Orthogonality
      with Wild Type and Ala/Gly-Gatekeeper Kinases.
AB  - Analogue-sensitive (AS) kinases contain large to small mutations in the
      gatekeeper position rendering them susceptible to inhibition with bulky analogues
      of pyrazolopyrimidine-based Src kinase inhibitors (e.g., PP1). This "bump-hole"
      method has been utilized for at least 85 of ~520 kinases, but many kinases are
      intolerant to this approach. To expand the scope of AS kinase technology, we
      designed type II kinase inhibitors, ASDO2/6 (analogue-sensitive "DFG-out" kinase
      inhibitors 2 and 6), that target the "DFG-out" conformation of Cys-gatekeeper
      kinases with submicromolar potency. We validated this system in vitro against
      Greatwall kinase (GWL), Aurora-A kinase, and cyclin-dependent kinase-1 and in
      cells using M110C-GWL-expressing mouse embryonic fibroblasts. These Cys
      gatekeeper kinases were sensitive to ASDO2/6 inhibition but not AS kinase
      inhibitor 3MB-PP1 and vice versa. These compounds, with AS kinase inhibitors,
      have the potential to inhibit multiple AS kinases independently with applications
      in systems level and translational kinase research as well as the rational design
      of type II kinase inhibitors targeting endogenous kinases.

PMID- 30239187
TI  - Electrochemical Oxidation of Atrazine and Clothianidin on Bi-doped
      SnO<sub>2</sub>-Ti<sub>n</sub>O<sub>2n-1</sub> Electrocatalytic Reactive
      Electrochemical Membranes.
AB  - This research focused on improving mineralization rates during the advanced
      electrochemical oxidation treatment of agricultural water contaminants. For the
      first time, bismuth-doped tin oxide (BDTO) catalysts were deposited on Magneli
      phase (Ti<sub>n</sub>O<sub>2n-1</sub>, n = 4-6 ) reactive electrochemical
      membranes (REMs). Terephthalic acid (TA) was used as OH<sup>?</sup> probe,
      whereas atrazine (ATZ) and clothianidin (CDN) were chosen as model agricultural
      water pollutants. The BDTO-deposited REMs (REM/BDTO) showed higher compound
      removal than the REM, due to enhanced OH<sup>?</sup> production. At 3.5 V/SHE
      complete mineralization of TA, ATZ, and CDN was achieved for the REM/BDTO upon a
      single pass in the reactor (residence time ~ 3.6 s). The energy consumption for
      REM/BDTO was as much as 31-fold lower than the REM, with minimal energy
      consumption per log removal of < 0.53 kWh m<sup>-3</sup> for TA (3.5 V/SHE), <
      0.42 kWh m<sup>-3</sup for ATZ (3.0 V/SHE), and 0.83 kWh m<sup>-3</sup> for CDN
      (3.0 V/SHE) with REM/BDTO/EDT. Density functional theory simulations provided
      potential dependent activation energy profiles for ATZ, CDN, and various
      oxidation products. Efficient mass transfer and a reaction mechanism involving
      direct electron transfer and reaction with OH<sup>?</sup> were responsible for
      the rapid and complete mineralization of ATZ and CDN at very short residence
      times.

PMID- 30239188
TI  - Direct Synthesis of Conformal Layered Protonated Titanate Nanoarray Coatings on
      Various Substrate Surfaces Boosted by Low-Temperature Microwave-Assisted
      Hydrothermal Synthesis.
AB  - Layered protonated titanates (LPTs) are promising support materials for catalytic
      applications because their high surface area and cation exchange capacity provide
      the possibility of achieving a high metal dispersion. However, the reported LPT
      nanomaterials are mainly limited to free-standing nanoparticles (NPs) and usually
      require high temperature and pressure conditions with extended reaction time. In
      this work, a high-throughput microwave-assisted hydrothermal method was developed
      for the direct synthesis of conformal LPT nanoarray coatings onto the three
      dimensional honeycomb monoliths as well as other substrate surfaces at low
      temperature (75-95  degrees C) and pressure (1 atm). Using TiCl3 as the titanium
      source, H2O2 as the oxidant, and hydrochloric acid as the pH controller, a
      peroxotitanium complex (PTC) was formed and identified to play an essential role
      for the formation of LPT nanoarrays. The gaseous O2 released during the
      decomposition of PTC promotes the mass transfer of the precursors, making this
      method applicable to substrates with complex geometries. With the optimized
      conditions, a growth rate of 42 nm/min was achieved on cordierite monolith
      substrates. When loaded with Pt NPs, the LPT nanoarray-based monolithic catalysts
      showed excellent low-temperature catalytic activity for CO and hydrocarbon
      oxidation as well as satisfactory hydrothermal stability and mechanical
      robustness. The low temperature and pressure requirements of this facile
      hydrothermal method overcome the size- and pressure-seal restrictions of the
      reactors, making it feasible for scaled production of LPT nanoarray-based devices
      for various applications.

PMID- 30239189
TI  - Label-Free SERS Quantum Semiconductor Probe for Molecular-Level and in Vitro
      Cellular Detection: A Noble-Metal-Free Methodology.
AB  - Accurate in vitro molecular-level analysis is an essential step prior to in vivo
      and clinical application for early diagnosis and cancer treatment. Among the
      diagnostic techniques, surface-enhanced Raman scattering (SERS) biosensing has
      shown growing potential due to its noninvasive and real-time characterization of
      the biomolecules. However, the application of SERS biosensing is mostly limited
      to the plasmonic noble metals, in the form of either nanoparticles or tips and
      substrates (fixed probe), on which surface plasmon resonance (SPR) is the
      prominent enhancement principle. The semiconductor quantum particles have been
      explored in several optoelectronics applications, but have never been reported to
      be exploited as a means of surface-enhanced Raman scattering (SERS) for molecular
      level and intracellular sensing. Here, we report on the new generation of noble
      metal-free SERS probe; Si@SiO2 quantum probe (Si@SiO2 Q-probe) whose affinity to
      functional groups not only imitates a self-driven labeling attribution that
      enables charge transfer (CT) as an augmented enhancement principle but also its
      mobile nature in miniaturized scale facilitates endocytosis for in situ live cell
      biosensing. Moreover, a significant enhancement factor of 106 of rhodamine 6G
      (R6G) and 107 of glutathione (GSH) at ~5 * 10-12 pM concentration has been
      achieved that is comparable to inherently plasmonic noble metals. Our results
      showed a capability of the Si@SiO2 Q-probe to unveil the "biochemical
      fingerprint" of substantial components of mammalian and cancerous cervical cells,
      which leads to diagnosis of cervical cancer. These unique attributions of the
      Si@SiO2 Q-probe can provide better insight into cell mutation and malignancy.

PMID- 30239190
TI  - A Minimalist Approach for Distinguishing Individual Lanthanide Ions Using
      Multivariate Pattern Analysis.
AB  - To discriminate among the 14 trivalent lanthanide ions, curcumin, a naturally
      occurring, nontoxic, off-the-shelf, commercially available compound containing a
      single fluorophore, was chosen as a probe in the water media at pH 6.8 and pH
      8.2. By measuring the emission and absorption spectra of the probe, under the
      different pH conditions, and by performing linear discriminant analysis on the
      data, 14 Ln3+ ions were discriminated. Additionally, an easy tool for the
      nonspecialists was developed with easily available household substances, using a
      smartphone app, which added an extra advantage to this single probe. This probe
      possesses advantageous features in terms of low-cost and instant on-site
      detection of the lanthanide ions.

PMID- 30239191
TI  - A Colorimetric Sensor for the Visual Detection of Azodicarbonamide in Flour Based
      on Azodicarbonamide-Induced Anti-Aggregation of Gold Nanoparticles.
AB  - Azodicarbonamide (ADA) in flour products can be converted into carcinogenic
      biurea and semicarbazide hydrochloride after baking. Thus, it is mandatory to
      determine ADA in flour. We herein developed a colorimetric method for the rapid
      and visual detection of ADA in flour based on glutathione (GSH)-induced gold
      nanoparticles (AuNPs) aggregation and specific reaction between ADA and GSH. The
      GSH can react to AuNPs via Au-SH covalent bond to form a network structure, which
      leads to AuNPs aggregation to produce color change, whereas ADA can specifically
      react with GSH to lead to the coupling of two GSH molecules, which makes GSH lose
      a -SH group and thus decreases the aggregation degree of AuNPs induced by GSH.
      This provided a platform for field-portable colorimetric detection of ADA. The
      colorimetric sensor can be used to detect as little as 0.33 MUM (38.3 ppb) of ADA
      by naked eye observation and 0.23 MUM (26.7 ppb) of ADA by spectrophotometry
      within 2 h. The method was successfully used to detect ADA in flour with a
      recovery of 91-104% and a relative standard deviation (RSD) < 6%. The visual
      detection limit of sensor is lower than the ADA limitation in flour (45 mg/kg),
      which makes the sensor a potential approach for the instrument-free visual and on
      site detection of ADA in flour.

PMID- 30239193
TI  - In Silico Protein Design Promotes the Rapid Evolution of Industrial Enzymes.

PMID- 30239192
TI  - Selective Enrichment of Phosphopeptides and Phospholipids from Biological
      Matrixes on TiO2 Nanowire Arrays for Direct Molecular Characterization by
      Internal Extractive Electrospray Ionization Mass Spectrometry.
AB  - Rapid analysis of phosphopeptides and phospholipids in biological matrixes is of
      significant interest in multiple disciplines of life sciences. Herein, trace
      phospholipids in human plasma, whole blood, and undiluted human urine as well as
      phosphopeptides in protein digest were selectively captured on a homemade array
      of TiO2 nanowires for sensitive characterization by internal extractive
      electrospray ionization mass spectrometry (TiO2-iEESI-MS). Sequential release of
      captured chemicals from TiO2 array was achieved by tuning pH of the extraction
      solvent. A single sample analysis, including sample loading, chemical extraction
      and MS detection, was accomplished within 3 min. As far as the quantification of
      phospholipids, acceptable linearity ( R2 >= 0.9985) and relative standard
      deviations (RSDs <= 8.9%) were obtained within the range of 0.1-500 MUg L-1 for
      LysoPC(14:0) and LysoPC(16:0) in raw urine samples. Limit of detection (LOD) <=
      0.025 MUg L-1 and recovery rates of 94.8-101.6% were obtained for these
      phospholipids. As far as the quantification of phosphopeptides, R2 >= 0.9994 and
      RSDs <= 9.2% within the range of 0.3-200 MUg L-1 were obtained for two
      phosphopeptides in nonphosphopeptides mixtures. LODs <= 0.09 MUg L-1 and recovery
      rates of 83.4-107.0% were obtained for these phosphopeptides. On the basis of the
      orthogonal partial least-squares discriminant analysis, TiO2-iEESI-MS patterns
      from the blood of 46 patients with ovarian cancer were confidently discriminated
      from the MS patterns of 46 healthy volunteers. Our results indicate the strong
      potential of TiO2-iEESI-MS approach for the selective detection of trace
      phosphopeptides and phospholipids in various biological matrixes with high
      sensitivity, high specificity, low sample consumption, and high throughput.

PMID- 30239194
TI  - Technetium and Rhenium Schiff Base Compounds for Nuclear Medicine: Syntheses of
      Rhenium Analogues to 99mTc-Furifosmin.
AB  - Rhenium, the third-row congener of technetium, is often used to develop the
      macroscopic chemistry of potential 99mTc diagnostic radiopharmaceuticals. The
      rhenium analogues to 99mTc-furifosmin are being developed for potential
      radiotherapy of multidrug-resistant tumors. Complexes of the form trans
      [MIII(PR3)2(N2O2-Schiff base)]+ are of interest for the potential imaging and
      treatment of multidrug-resistant tumors. Reaction of the tetradentate Schiff
      ligand 4,4'-[(1 E,1' E)-[ethane-1,2
      diylbis(azanylylidene)]bis(methanylylidene)]bis(2,2,5,5-tetramethyl-2,5
      dihydrofuran-3-ol) (tmf2enH2) with the M(V) starting materials ( nBu4N)[TcOCl4]
      and ( nBu4N)[ReOCl4] gave the monomeric products trans-[TcOCl(tmf2en)] and trans
      [ReOCl(tmf2en)], respectively. Reduction of in situ formed trans-[ReOCl(tmf2en)]
      by various tertiary phosphines yielded disubstitued Re(III) products of the
      general type trans-[ReIII(PR3)2(tmf2en)]+. The rhenium(III) compounds were found
      to be water-soluble and stable in aqueous solution. Reversible ReIII/ReIV and
      ReIII/ReII redox processes were observed at about 0.8-0.9 and -0.65 to -0.8 V,
      respectively, for each of the rhenium(III) species. Reaction of in situ formed
      trans-TcOCl(tmf2en) with triethylphosphine yielded the reduced, disubstituted
      trans-[Tc(PEt3)2(tmf2en)]PF6. A reversible TcIII/TcII redox couple was observed
      for the technetium(III) species, about 200 mV less negative than their
      rhenium(III) analogues, in addition to an irreversible TcIII/TcIV process. All
      compounds were characterized using conventional spectroscopic techniques, single
      crystal X-ray crystallography, and cyclic voltammetry.

PMID- 30239195
TI  - One-Pot Synthesis of N-Graphene Quantum Dot-Functionalized I-BiOCl Z-Scheme
      Cathodic Materials for "Signal-Off" Photoelectrochemical Sensing of Chlorpyrifos.
AB  - A Z-scheme I-BiOCl/N-GQD (i.e., nitrogen-doped graphene quantum dot)
      heterojunction was prepared by a one-pot precipitation method at room
      temperature. The doped iodine decreased the band gap of BiOCl, the introduced N
      GQDs enhanced light harvesting and prolonged the photogenerated electron
      lifetime, and the resultant Z-scheme heterojunction promoted the spatial
      separation of interfacial charges. Thus, the composite showed high
      photoelectrochemical activity and a big cathodic photocurrent signal. On the
      basis of the coordination of chlorpyrifos with surface Bi(III) of the composite,
      a cathodic photoelectrochemical sensor was constructed for the selective
      detection of chlorpyrifos. In this case, chlorpyrifos decreased the lifetime of
      photogenerated electrons, so the photocurrent became small. Furthermore, the
      photocurrent changed and the logarithm of chlorpyrifos concentration presented a
      linear relationship. The linear range was 0.3-80 ng mL-1, and the limit of
      detection was estimated to be 0.01 ng mL-1 (defined as S/N = 3). The present
      strategy can also be used for the design and fabrication of other PEC sensors
      suitable for different analytes.

PMID- 30239196
TI  - Vibrational Circular Dichroism Sheds New Light on the Competitive Effects of
      Crowding and beta-Synuclein on the Fibrillation Process of alpha-Synuclein.
AB  - The effects of crowding, using the crowding agent Ficoll 70, and the presence of
      beta-synuclein on the fibrillation process of alpha-synuclein were studied by
      spectroscopic techniques, transmission electron microscopy, and thioflavin T
      assays. This combined approach, in which all techniques were applied to the same
      original sample, generated an unprecedented understanding of the effects of these
      modifying agents on the morphological properties of the fibrils. Separately,
      crowding gives rise to shorter mutually aligned fibrils, while beta-synuclein
      leads to branched, short fibrils. The combination of both effects leads to short,
      branched, mutually aligned fibrils. Moreover, it is shown that the nondestructive
      technique of vibrational circular dichroism is extremely sensitive to the length
      and the higher-order morphology of the fibrils.

PMID- 30239197
TI  - Ruthenium(II)-Polypyridyl Compounds with pi-Extended Nitrogen Donor Ligands
      Induce Apoptosis in Human Lung Adenocarcinoma (A549) Cells by Triggering Caspase
      3/7 Pathway.
AB  - Ru(II)-polypyridyl complexes exhibit antitumor properties that can be
      systematically tailored by means of adjusting the ligand environment. In this
      work, the effect of incorporating pi-extended moieties into anionic N?O- based
      chelating ligands on the cytotoxic properties of Ru compounds is explored. Four
      new Ru(II) complexes, [Ru(bpy)2(dphol)][PF6] (1; bpy = 2,2'-bipyridine, dphol =
      dibenzo[ a, c]phenazin-10-olate), [Ru(phen)2(dphol)][PF6] (2; phen = 1,10
      phenanthroline), [Ru(bpy)2(hbtz)][PF6] (3; hbtz = 2-(benzo[ d]thiazol-2
      yl)phenolate), and [Ru(phen)2(hbtz)][PF6] (4) were synthesized and thoroughly
      characterized. In vitro cytotoxicity was investigated in human lung
      adenocarcinoma (A549) cells, which revealed that 4 is the most cytotoxic compound
      (IC50 = 0.8 MUM) in the series including a control compound [Ru(bpy)2(quo)][PF6]
      (5; quo = 8-hydroxyquinolinate) and is nearly 8-fold more cytotoxic than
      cisplatin. An investigation of the mechanism of cell death led to the finding
      that compounds 1-4 disrupt the mitochondrial transmembrane potential (DeltaPsim)
      in a concentration-dependent fashion, which is an event associated with the
      intrinsic pathway of apoptosis. Moreover, compound 4 triggers the activity of
      caspase-3/7, which eventually induces the apoptotic cellular death of A549 cells.
      Thus, increasing the overall lipophilicity of the Ru compounds by introducing pi
      extended moieties in the anionic N?O- ligand is a successful strategy for
      realizing a new family of pro-apoptotic compounds with a [RuIIN5O]+ coordination
      environment.

PMID- 30239198
TI  - Construction of Challenging Proline-Proline Junctions via Diselenide-Selenoester
      Ligation Chemistry.
AB  - Polyproline sequences are highly abundant in prokaryotic and eukaryotic proteins,
      where they serve as key components of secondary structure. To date, construction
      of the proline-proline motif has not been possible owing to steric congestion at
      the ligation junction, together with an n -> pi* electronic interaction that
      reduces the reactivity of acylated proline residues at the C-terminus of
      peptides. Here, we harness the enhanced reactivity of prolyl selenoesters and a
      trans-gamma-selenoproline moiety to access the elusive proline-proline junction
      for the first time through a diselenide-selenoester ligation-deselenization
      manifold. The efficient nature of this chemistry is highlighted in the high
      yielding one-pot assembly of two proline-rich polypeptide targets, submaxillary
      gland androgen regulated protein 3B and lumbricin-1. This method provides access
      to the most challenging of ligation junctions, thus enabling the construction of
      previously intractable peptide and protein targets of increasing structural
      complexity.

PMID- 30239199
TI  - Tunable Synthesis of 2-Ene-1,4-diones, 4-Hydroxycyclopent-2-en-1-ones, and 2
      (Furan-3-yl)acetamides via Palladium-Catalyzed Cascade Reactions of Allenols.
AB  - An efficient and regioselective synthesis of 2-ene-1,4-diones, 4-hydroxycyclopent
      2-en-1-ones, or 2-(furan-3-yl)acetamides is successfully realized through
      palladium-catalyzed one-pot multicomponent reactions of allenols with aryl
      iodides and carbon monoxide in the presence of tertiary amines. Interestingly,
      the selectivity depends on the substitution patterns of the allenol substrates.
      To be specific, from the reaction of allenols with no substituent attached on the
      internal position of the allenic moiety, 2-ene-1,4-diones or 4-hydroxycyclopent-2
      en-1-ones were formed selectively through carbonylation of aryl iodide followed
      by acylation of allenol with the in situ formed acyl palladium species, beta
      hydride elimination of the in situ formed allyl palladium complex, and further
      tautomerization or intramolecular aldol reaction. From the reaction of allenols
      bearing a substituent at the internal position of the allenic unit, on the other
      hand, diversely substituted 2-(furan-3-yl)acetamides were formed through a
      cascade process combining carbonylation of aryl iodide, acylation, and
      carbonylation of allenol followed by intramolecular condensation and amination by
      tertiary amine featuring an oxidant-free C-N bond cleavage.

PMID- 30239200
TI  - Comprehensive Study of the Self-Assembly of Phospholipid Nanodiscs: What
      Determines Their Shape and Stoichiometry?
AB  - Phospholipid nanodiscs have quickly become a widely used platform for studies of
      membrane proteins. However, the molecular self-assembly process that ultimately
      should place a membrane protein inside a nanodisc is not well understood. This
      poses a challenge for a successful high-yield reconstitution of general membrane
      proteins into nanodiscs. In the present work, the self-assembly process of POPC
      MSP1D1 nanodiscs was carefully investigated by systematically modulating the
      reconstitution parameters and probing the effect with a small-angle X-ray
      scattering analysis of the resulting nanodiscs. First, it was established that
      nanodiscs prepared using the standard protocol followed a narrow but significant
      size distribution and that the formed nanodiscs were stable at room temperature
      over a time range of about a week. Systematic variation of the POPC/MSP1D1
      stoichiometry of the reconstitution mixture showed that a ratio of less than 75:1
      resulted in lipid-poor nanodiscs, whereas ratios of 75:1 and larger resulted in
      nanodiscs with constant POPC/MSP1D1 ratios of 60:1. A central step in the self
      assembly process consists in adding detergent-absorbing resin beads to the
      reconstitution mixture to remove the reconstitution detergent. Surprisingly, it
      was found that this step did not play a significant role for the shape and
      stoichiometry of the formed nanodiscs. Finally, the effect of the choice of
      detergent used in the reconstitution process was investigated. It was found that
      detergent type is a central determining factor for the shape and stoichiometry of
      the formed nanodiscs. A significantly increasing POPC/MSP1D1 stoichiometry of the
      formed nanodiscs was observed as the reconstitution detergent type is changed in
      the order: Tween80, DDM, Triton X-100, OG, CHAPS, Tween20, and Cholate, but with
      no simple correlation to the characteristics of the detergent. This emphasizes
      that the detergents optimal for solution storage and crystallization of membrane
      proteins, in particular DDM, should not be used alone for nanodisc
      reconstitution. However, our data also show that when applying mixtures of the
      reconstitution detergent cholate and the storage detergents DDM or OG, cholate
      dominates the reconstitution process and nanodiscs are obtained, which resemble
      those formed without storage detergents.

PMID- 30239201
TI  - Interaction between Surface Charge-Modified Gold Nanoparticles and Phospholipid
      Membranes.
AB  - This report clarifies the interaction of surface charge-modified gold
      nanoparticles (AuNPs) with phospholipid membranes, which is helpful to understand
      the antibacterial mechanism of positive charge-modified AuNPs to Gram-negative
      bacteria. Although the simulated bacterial cell membranes as a whole are
      negatively charged, the local electrostatic repulsive interaction between the
      positive charge-coated AuNPs and the small-sized flexible cationic head group of
      dioleyl phosphatidylethanolamine molecules induces the phase transformation of
      the simulated bacterial cell membranes from a lamellar to an inverted hexagonal
      phase. Transmembrane pores with a diameter of about 3.0 nm in the inverted
      hexagonal structure would result in the destruction of cell membrane function.
      Such an interaction of positive charge-modified AuNPs with the membrane mimics
      provides a promising route to develop new antibacterial agents by modifying
      positive charges on the surface of nanoparticles.

PMID- 30239202
TI  - Arrested Coalescence of Viscoelastic Droplets: Ellipsoid Shape Effects and
      Reorientation.
AB  - The stable configurations formed by two poroelastic, ellipsoid-shaped droplets
      during their arrested coalescence have been investigated using micromanipulation
      experiments. Ellipsoidal droplets are produced by millifluidic emulsification of
      petrolatum into a yield stress fluid that preserves their elongated shape. The
      liquid meniscus between droplets can transmit stress and instigate movement of
      the droplets, from their initial relative position, in order to minimize doublet
      surface energy. The action of the liquid meniscus causes the ellipsoidal droplets
      to undergo rolling and reorientation events because of their unique ellipsoid
      shape and associated variation in the surface curvature. The final configuration
      of the droplets is controlled by the balance between interfacial Laplace pressure
      and internal elasticity, as well as a constraint force that resists complete
      minimization of surface energy. Geometric and surface energy calculations are
      used to map the possible and most likely configurations of the droplet pairs.
      Experimental deviations from the calculations indicate the magnitude and
      potential origin of the constraint force resisting full equilibration. Droplet
      aspect ratio and elasticity are both shown to influence the degree of
      reorientation and stability of the droplets at energy extrema. Higher aspect
      ratios drive greater reorientation and better agreement with final doublet
      configurations predicted by energy minimization. Lower elasticity droplets
      undergo secondary deformations at high aspect ratios, further broadening the
      space of possible morphologies.

PMID- 30239203
TI  - Understanding the Structure of the Hydrogen Bond Network and Its Influence on
      Vibrational Spectra in a Prototypical Aprotic Ionic Liquid.
AB  - Analysis of the hydrogen bond network in aprotic ionic liquid 1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM-TFSI) has been
      performed based on structures obtained from ab initio or classical molecular
      dynamics simulations. Statistics of different donor and acceptor atoms and the
      amount of chelating or bifurcated bonds has been presented. Most of the hydrogen
      bonds in EMIM-TFSI are formed with oxygen atoms as hydrogen acceptors; and the
      most probable bifurcated bonds are those with a mixed pair of oxygen and nitrogen
      acceptors. Spectral graph analysis has shown that the cations may form hydrogen
      bonds with up to five different anions and the connectivity of the whole hydrogen
      bond network is supported mainly by H-O bonds. In the structures of the liquid
      simulated via force field-based dynamics, the number of hydrogen bonds is smaller
      and fluorine atoms are the most favored hydrogen acceptors. One-dimensional
      potential energy profiles for hydrogen atom displacements and corresponding
      vibrational frequencies have been calculated for selected C-H bonds. Individual C
      H stretching frequencies vary by 200-300 cm-1, indicating differences in local
      environment of hydrogen atoms forming C-H...O hydrogen bonds.

PMID- 30239204
TI  - Comparison of Electron and Ion Emission from Xenon Cluster-Induced Ignition of
      Helium Nanodroplets.
AB  - The charging dynamics of helium droplets driven by embedded xenon cluster
      ignition in strong laser fields is studied by comparing the abundances of helium
      and highly charged Xe ions to the electron signal. Femtosecond pump-probe
      experiments show that near the optimal delay for highly charged xenon the
      electron yield increases, especially at low energies. The electron signature can
      be traced back to the ionization of the helium environment by Xe seed electrons.
      Accompanying molecular dynamics simulations suggest a two-step ionization
      scenario in the Xe-He core-shell system. In contrast to xenon, the experimental
      signal of the helium ions, as well as low-energy electron emission show a
      deviating delay dependence, indicating differences in the temporal and spacial
      development of the charge state distribution of Xe core and He surrounding. From
      the pump-probe dependence of the electron emission, effective temperatures can be
      extracted, indicating the nanoplasma decay.

PMID- 30239205
TI  - In-Depth Quantitative Proteomic Analysis of Trophozoites and Pseudocysts of
      Trichomonas vaginalis.
AB  - Trichomonas vaginalis is a sexually transmitted anaerobic parasite that infects
      humans causing trichomoniasis, a common and ubiquitous sexually transmitted
      disease. The life cycle of this parasite possesses a trophozoite form without a
      cystic stage. However, the presence of nonproliferative and nonmotile, yet viable
      and reversible spherical forms with internalized flagella, denominated
      pseudocysts, has been commonly observed for this parasite. To understand the
      mechanisms involved in the formation of pseudocysts, we performed a mass
      spectrometry-based high-throughput quantitative proteomics study using a label
      free approach and functional assays by biochemical and flow cytometric methods.
      We observed that the morphological transformation of trophozoite to pseudocysts
      is coupled to (i) a metabolic shift toward a less glycolytic phenotype; (ii)
      alterations in the abundance of hydrogenosomal iron-sulfur cluster (ISC) assembly
      machinery; (iii) increased abundance of regulatory particles of the ubiquitin
      proteasome system; (iv) significant alterations in proteins involved in adhesion
      and cytoskeleton reorganization; and (v) arrest in G2/M phase associated with
      alterations in the abundance of regulatory proteins of the cell cycle. These data
      demonstrate that pseudocysts experience important physiological and structural
      alterations for survival under unfavorable environmental conditions.

PMID- 30239206
TI  - Lipid Bilayer Disruption by Amphiphilic Janus Nanoparticles: The Role of Janus
      Balance.
AB  - Amphiphilic nanoparticles are known to cause defects in lipid bilayers. However,
      we have shown recently that their disruptive effects are significantly enhanced
      when surface charges and hydrophobic groups are spatially segregated on opposite
      hemispheres of a single particle. Using the same amphiphilic cationic/hydrophobic
      Janus particle system, here we investigate the role of the hydrophilic-lipophilic
      balance of the particles (namely the Janus balance) in their interaction with
      zwitterionic lipid bilayers. We show that Janus nanoparticles induce holes in
      lipid bilayers only when the hydrophobic side of particles occupies 20% or more
      of their surfaces. Beyond this threshold, the larger the hydrophobic surface
      area, the more attractive the particles are to lipid bilayers, and a lower
      particle concentration is needed for causing defects in the bilayers. The results
      establish a quantitative relationship between the surface coverage of
      hydrophobicity on the Janus particles and the particle-induced disruption to the
      lipid membranes.

PMID- 30239207
TI  - On the Natural Structure of Amino Acid Patterns in Families of Protein Sequences.
AB  - All known terrestrial proteins are coded as continuous strings of ~20 amino
      acids. The patterns formed by the repetitions of elements in groups of finite
      sequences describes the natural architectures of protein families. We present a
      method to search for patterns and groupings of patterns in protein sequences
      using a mathematically precise definition for "repetition", an efficient
      algorithmic implementation and a robust scoring system with no adjustable
      parameters. We show that the sequence patterns can be well-separated into
      disjoint classes according to their recurrence in nested structures. The
      statistics of the occurrences of patterns indicate that short repetitions are
      sufficient to account for the differences between natural families and randomized
      groups of sequences by more than 10 standard deviations, while contiguous
      sequence patterns shorter than 5 residues are effectively random in their
      occurrences. A small subset of patterns is sufficient to account for a robust
      "familiarity" definition between arbitrary sets of sequences.

PMID- 30239209
TI  - Palladium-Catalyzed [2 + 2 + 2] Annulation via Transformations of Multiple C-H
      Bonds: One-Pot Synthesis of Diverse Indolo[3,2- a]carbazoles.
AB  - A Pd-catalyzed novel cascade reaction has been developed for the synthesis of
      indolo[3,2 a]carbazoles involving multiple C-H transformation-annulations between
      the indoles and alkynes. The method involves molecular oxygen as the sole oxidant
      and is an effective and step-economic process.

PMID- 30239208
TI  - Hydrogen Sulfide-Activatable Second Near-Infrared Fluorescent Nanoassemblies for
      Targeted Photothermal Cancer Therapy.
AB  - Near-infrared (NIR)-II fluorescence agents hold great promise for deep-tissue
      photothermal therapy (PTT) of cancers, which nevertheless remains restricted by
      the inherent nonspecificity and toxicity of PTT. In response to this challenge,
      we herein develop a hydrogen sulfide (H2S)-activatable nanostructured
      photothermal agent (Nano-PT) for site-specific NIR-II fluorescence-guided PTT of
      colorectal cancer (CRC). Our in vivo studies reveal that this theranostic Nano-PT
      probe is specifically activated in H2S-rich CRC tissues, whereas it is
      nonfunctional in normal tissues. Activation of Nano-PT not only emits NIR-II
      fluorescence with deeper tissue penetration ability than conventional fluorescent
      probes but also generates high NIR absorption resulting in efficient photothermal
      conversion under NIR laser irradiation. Importantly, we establish NIR-II imaging
      guided PTT of CRC by applying the Nano-PT agent in tumor-bearing mice, which
      results in complete tumor regression with minimal nonspecific damages. Our
      studies thus shed light on the development of cancer biomarker-activated PTT for
      precision medicine.

PMID- 30239210
TI  - Utilization and Challenges of Continuous Glucose Monitoring in Sensor-Augmented
      Pump Therapy: A Patient Experience Analysis.

PMID- 30239211
TI  - Steroid Injection and Open Trigger Finger Release Outcomes: A Retrospective
      Review of 999 Digits.
AB  - BACKGROUND: Open surgical release of the A1 pulley is the definitive treatment
      for the common hand condition of trigger finger, or inflammatory stenosing
      tenosynovitis. Anecdotal evidence among hand surgeons has questioned whether or
      not recent steroid injection may be related to complications following open
      trigger finger release, particularly wound infection, but no studies have
      primarily studied this connection to date. We aimed to determine whether recent
      steroid injection was associated with postoperative surgical infections. METHODS:
      We performed a retrospective chart review of 780 adult patients who had undergone
      open trigger finger release of 999 digits by 6 fellowship-trained hand surgeons
      at three affiliated hospital settings from January 1, 2014, to January 1, 2016.
      Data on timing of steroid injections relative to surgery, number of steroid
      injections, concomitant conditions, use of antibiotics, and postoperative
      complications including infections were gathered. RESULTS: Steroid injection
      timing relative to subsequent operative intervention correlated with
      postoperative surgical site infection in trigger finger release. Older age and
      decreasing days between steroid injection and surgery correlated with infection
      rates. Other factors found to be associated with infection rates included
      smoking, use of preoperative antibiotics, and use of lidocaine with epinephrine.
      The other factors examined did not correlate with infection rates. CONCLUSIONS:
      Steroid injection, smoking, increasing age, lesser number of days between steroid
      injection and surgery, and use of lidocaine with epinephrine are risk factors for
      postoperative trigger surgical infections. We recommend careful preoperative
      counseling regarding higher wound healing risks for smokers, avoidance of steroid
      injections immediately prior to an operative date, and scheduling operative dates
      that tend to be greater than 80 days from the date of last steroid injection. We
      also recommend avoidance of epinephrine in the local anesthetic solution, as this
      may minimize surgical site infection risks.

PMID- 30239212
TI  - Evaluation of a Handheld Gluten Detection Device.
AB  - A portable, handheld gluten detection device, the Nima sensor, is now available
      for consumers wishing to determine if gluten is present in food. By U.S.
      regulation, gluten-free foods should contain <20 ppm of gluten. Thirteen gluten
      free foods (muffins, three different types of bread, three different types of
      pasta, puffed corn snack, ice cream, meatballs, vinegar and oil salad dressing,
      oatmeal, and dark chocolate) were prepared; each food was spiked on a weight to
      weight basis with gluten levels of 0, 5, 10, 20, 30, 40, and 100 ppm before
      processing or preparation. Unprocessed and processed foods were tested with the
      handheld gluten sensor and by two gluten-specific enzyme-linked immunosorbent
      assays (ELISAs) on the basis of the R5 and G12 monoclonal antibodies,
      respectively. The portable gluten detection device detected gluten in all food
      types at the 30-ppm addition level, failing to detect gluten in only 5 (6.4%) of
      78 subsamples. At the 20-ppm addition level, the portable gluten detection device
      failed to detect gluten in one type of pasta but detected gluten residues in 63
      (87.5%) of 72 other subsamples. The device was able to detect gluten at the 10
      ppm addition level in 9 of the 13 food matrices (41 of 54 subsamples, 75.9%) but
      not in the three types of pasta and the puffed corn snack. The gluten-sensing
      device did not perform reliably at the 5-ppm addition level in 11 of 13 food
      matrices (exceptions: ice cream and muffins). In contrast, the ELISA methods were
      highly reliable at gluten addition levels of >=10 ppm in all food matrices. The
      portable gluten detection device yielded a low percentage of false-positive
      results (4 of 111, 3.6%) in these food matrices. Thus, this handheld portable
      gluten sensor performed reliably in the detection of gluten in foods having >=20
      ppm of added gluten with only 18 (5.9%) of 306 failures, if results of the one
      type of pasta are excluded. The device worked with greater reliability as the
      gluten levels in the foods increased.

PMID- 30239213
TI  - Xbox 360 Kinect Cognitive Games Improve Slowness, Complexity of EEG, and
      Cognitive Functions in Subjects with Mild Cognitive Impairment: A Randomized
      Control Trial.
AB  - OBJECTIVES: Physical activity and cognitive training are effective to enhance
      cognition in older patients with mild cognitive impairment (MCI). Xbox 360 Kinect
      cognitive games are a combination of physical activity and cognitive training.
      The objective of this study was to determine the short- and long-term effects of
      Xbox 360 Kinect cognitive games on slowness and complexity of
      electroencephalography (EEG) and cognitive functions in older subjects with MCI.
      MATERIALS AND METHODS: A clinical trial was conducted on 44 MCI subjects. Both
      males and females were randomized into experimental group (participated in Xbox
      360 Kinect cognitive games) and control group (range of motion exercises only and
      no Xbox 360 Kinect cognitive games). Subjects were assessed before and after one
      session of game intervention for short-term effects and after 6 weeks for long
      term effects. The outcome measures were the mini-mental state examination (MMSE),
      Montreal cognitive assessment scale (MoCA), trail making test (TMT) A and B, and
      slowness and complexity of EEG. RESULTS: After one session of game intervention,
      delta (0.704 +/- 0.025; P = 0.013), theta (0.128 +/- 0.009; P = 0.00127) waves,
      and complexity of EEG (0.642 +/- 0.042; P = 0.008) significantly improved, in
      eyes closed state. Whereas after 6 weeks intervention of games, delta (0.673 +/-
      0.029; P = 0.013), theta (0.129 +/- 0.013; P = 0.002), beta2 waves (0.044 +/-
      0.009; P = 0.046), complexity of EEG (0.051 +/- 0.042; P = 0.016), MMSE (26.25 +/
      0.347 vs. 23.722 +/- 0.731; P = 0.003), MoCA (25.65 +/- 0.310 vs. 22.00 +/-
      0.504; P = 0.0001), TMT-A (1.429 +/- 0.234 vs. 2.225 +/- 0.259; P = 0.028), and
      TMT-B (2.393 +/- 0.201 vs. 3.780 +/- 0.195; P = 0.0001) improved significantly.
      These changes were not observed in the control group. CONCLUSION: Xbox 360 Kinect
      games showed beneficial effects after short- and long-term intervention on MCI
      subjects. These games can serve as potential therapeutic candidates for MCI.

PMID- 30239215
TI  - Psychometric Properties of Figure Rating Scales in Children: The Impact of Figure
      Ordering.
AB  - This study examined psychometric properties of figure rating scales, particularly
      the effects of ascending silhouette ordering, in 153 children, 9 to 13 years old.
      Two versions of Collins's (1991) figural rating scale were presented: the
      original scale (figures arranged ascendingly) and a modified version (randomized
      figure ordering). Ratings of current and ideal figure were elicited and body
      dissatisfaction was calculated. All children were randomly assigned to one of two
      subgroups and completed both scale versions in a different sequence. There were
      no significant differences in figure selection and body dissatisfaction between
      the two figure orderings. Regarding the selection of the current figure, results
      showed that girls are more affected by the silhouette ordering than boys. Our
      results suggest that figure rating scales are both valid and reliable, whereby
      correlation coefficients reveal greater stability for ideal figure selections and
      body dissatisfaction ratings when using the scale with ascending figure ordering.

PMID- 30239214
TI  - Novel Bluetooth-Enabled Tubeless Insulin Pump: Innovating Pump Therapy for
      Patients in the Digital Age.
AB  - The Omnipod DASHTM Insulin Management System (Insulet Corp, Billerica, MA) is a
      discreet, tubeless, wearable insulin pump that holds up to 200 units of U-100
      insulin and delivers therapy through customizable basal rates and bolus amounts.
      This recently FDA-cleared system consists of the insulin pump ("Pod"), which is
      worn on body and delivers insulin, and the Personal Diabetes Manager (PDM), which
      is a handheld device used to wirelessly control and monitor the Pod
      functionality. The PDM can also be paired with the CONTOUR(r) NEXT ONE blood
      glucose (BG) meter (Ascensia Diabetes Care, Basel, Switzerland) to wirelessly
      receive BG readings. This review provides a detailed description of the Pod and
      PDM. Key features of the Pod are described, including the novel pump delivery
      mechanism, waterproof (IP28) housing design, and automated cannula insertion. The
      technology introduced in the new system, such as touchscreen PDM interface,
      Bluetooth(r) wireless technology, and wireless internet connectivity, is also
      presented. Last, Omnipod(r) Insulin Management System clinical data are reviewed,
      including early feasibility results for the Omnipod HorizonTM Automated Glucose
      Control hybrid closed-loop system.

PMID- 30239216
TI  - The Functionality of Communal Coping in Chronic Uncertainty Environments: The
      Context of Palestinian Refugees in Lebanon.
AB  - Most research suggests that communal coping, where a group of people own and act
      upon a shared stressor or uncertainty together, enhances mental health and
      fosters coping efficacy. The majority of this research, however, has been
      conducted in the United States in contexts where stress and uncertainty are
      relatively short-lived and with samples that are economically secure and
      moderately to highly educated. The purpose of this study was to understand how
      socio-emotional conditions, such as exposure to trauma and interparental
      conflict, influence the functionality of communal coping for adolescents in
      Palestinian refugee camps in Lebanon, where chronic uncertainty is normative. One
      hundred eighty-five Palestinian adolescents (M age = 15.75) residing in two
      refugee camps in Beirut, Lebanon completed a cross-sectional survey. The results
      showed that communal coping with immediate family members was only beneficial for
      adolescents' mental health and hopelessness when their parents had moderate to
      little conflict and not high levels of conflict. Similarly, when adolescents had
      experienced trauma, engaging in high levels of communal coping accentuated, as
      opposed to buffered, the harmful effects of uncertainty on mental health.

PMID- 30239217
TI  - Standards of Virtual Reality Application in Balance Training Programs in Clinical
      Practice: A Systematic Review.
AB  - OBJECTIVE: To determine the effect of virtual reality (VR) games on improving
      balance in different groups of neurological patients with a particular focus on
      the study quality and to determine the gold standard in VR training in these
      groups. MATERIALS AND METHODS: A systematic review of controlled trials published
      between January 2009 and December 2017 was conducted. The PubMed, SCOPUS,
      SPORTDiscus, and Medline databases were searched. Studies involved patients with
      stroke or Parkinson's disease or children with cerebral palsy. The Physiotherapy
      Evidence Database (PEDro) scale was used to assess the methodological quality of
      the included studies. RESULTS: A total of 20 studies met the inclusion criteria.
      The PEDro scores ranged from 4 to 8 points. Analysis of the rehabilitation
      programs revealed a very large discrepancy in the planned volume of exercises in
      different subgroups of patients. CONCLUSIONS: Overall, the comparison of VR
      interventions between conventional rehabilitation and no intervention exhibited
      significantly better results. However, these results should be interpreted with
      great caution due to the large diversity of the systems, games, and training
      volume used in the VR therapy. In all included studies, only several articles
      included objective methods to assess the effect of VR. In addition, most of the
      articles showed a high risk of bias, such as a lack of randomization and blinding
      or a small sample size. That is why further well-designed randomized control
      trials are required to evaluate the influence of VR on balance in different
      groups of neurological patients.

PMID- 30239218
TI  - Orthodontic appliances did not increase risk of dental caries and periodontal
      disease under preventive protocol.
AB  - OBJECTIVES:: To assess periodontal parameters and microbial species levels after
      orthodontic appliance placement in patients who received oral hygiene
      instructions and who were monitored and motivated throughout the study. MATERIALS
      AND METHODS:: The Periodontal Index was recorded and saliva collection was
      performed before (T0) and 30 (T1), 60 (T2), and 90 (T3) days after orthodontic
      appliance placement in 15 patients (mean age 17.53 +/- 8.0 years). Analysis was
      carried out using checkerboard DNA-DNA hybridization. Nonparametric statistical
      analysis was performed. RESULTS:: The Periodontal Index did not change. The total
      amount of the purple and red complexes and Candida species showed a significant
      decrease from T2. The green, yellow, and orange complex showed a significant
      decrease at T3. The specific species analysis showed that Prevotella nigrescens,
      Pseudomonas putida, Fusobacterium periodonticum, Pseudomonas aeruginosa,
      Peptostreptococcus anaerobius, and Tanerella forsythia showed high incidence
      before bonding, and their levels decreased at T2 and T3. Only Porphyromonas
      gingivalis showed increased levels at T2 and displayed the highest level at T3.
      The Streptococcus group decreased their levels from T2 onward. CONCLUSIONS:: A
      dynamic change in microbial levels was identified. The decrease in the levels of
      complexes present was only possible due to the mechanical method of oral hygiene
      implemented in this sample.

PMID- 30239220
TI  - Surgical Fixation of Metacarpal Shaft Fractures Using Absorbable Implants: A
      Systematic Review of the Literature.
AB  - BACKGROUND: Despite the proven efficacy and advantages of absorbable implants,
      their use for metacarpal shaft fixation has been limited. This is likely due to
      the high reported complication rates in early studies with polyglycolic acid
      (PGA) implants, notably high rates of noninfectious inflammatory reaction (5%
      25%), occurring up to 30 weeks after fixation. The objective of this study was to
      assess the clinical outcomes of newer absorbable plates and screws in the
      treatment of metacarpal shaft fractures. METHODS: The authors performed a
      systematic search of the PubMed, Ovid MEDLINE, and EMBASE databases dating from
      1946 to 2017. Primary outcome measures were the development of noninfectious
      inflammatory reaction and implant failure. RESULTS: A total of 42 metacarpal
      shaft fractures in 35 patients were included. The average follow-up time was 20.4
      months (n = 24; range: 3.6-61 months). Only 1 case (2.4%) of noninfectious
      inflammatory reaction was reported with polylactic acid (PLA) plates and PLA/PGA
      compounds. Noninfectious inflammatory reaction was observed in 4 out of the 9
      patients (44.4%) with a trimethylene carbonate/PLA compound. Symptoms appeared
      after an average time of 15.8 months (range: 12-19 months) post-fixation.
      Painless prolonged inflammation that resolved spontaneously within 6 months was
      reported in 7.1% of cases (n = 3). Implant failure with loss of fracture
      reduction was reported in 9.5% of cases (n = 4). CONCLUSIONS: Newer absorbable
      materials appear to have significantly lower rates of noninfectious inflammatory
      reaction than previously reported. When compared with metallic fixation of the
      metacarpal shaft, absorbable fixation appears to have comparable complication
      rates and biomechanical properties.

PMID- 30239219
TI  - Psychosocial and Human Factors During a Trial of a Hybrid Closed Loop System for
      Type 1 Diabetes Management.
AB  - BACKGROUND: Hybrid closed loop (HCL) systems are designed to automate insulin
      delivery to improve type 1 diabetes (T1D) outcomes and reduce user burden and
      distress. Because the systems only automate some aspects of diabetes care,
      psychosocial and human factors remain an important consideration in their use.
      Thus, we examined whether psychosocial and human factors (i.e., distress related
      to diabetes management, fear of hypoglycemia, and technology attitudes) would (1)
      change after using the system and (2) predict glycemic outcomes during the trial.
      SUBJECTS AND METHODS: Fourteen adults and 15 adolescents with T1D participated in
      a multisite clinical trial of an investigational version of the MiniMedTM 670G
      system (Medtronic, Northridge, CA) over 4 to 5 days in a semisupervised
      outpatient setting. Users completed surveys assessing psychosocial and human
      factors before beginning the HCL system and at the conclusion of the study. t
      Tests and regression analyses were conducted to examine whether these factors
      changed following trial exposure to the HCL system and predicted glycemic
      outcomes during the trial. RESULTS: Diabetes management distress decreased and
      diabetes technology attitudes became more positive over the trial period. Fear of
      hypoglycemia did not change over the trial period. There was a trend toward
      greater pretrial management distress predicting less time in range during the
      trial, controlling for time in range before the trial. CONCLUSIONS: Results
      suggest that this system is promising for enhancing technology attitudes and
      reducing management distress. Psychosocial factors, such as management distress,
      may negatively impact glycemic outcomes and should be a priority area for further
      investigation.

PMID- 30239221
TI  - Assessing the Proactive and Reactive Dimensions of Criminal Thought Process:
      Divergent Patterns of Correlation With Variable- and Person-Level Measures of
      Criminal Risk and Future Outcome.
AB  - The goal of this study was to determine whether measures of proactive and
      reactive criminal thinking display divergent patterns of correlation with outside
      criteria. A sample of 3,039 male medium-security federal prisoners who completed
      the Psychological Inventory of Criminal Thinking Styles (PICTS) served as
      participants in this study. Despite being highly correlated (r = .75), the PICTS
      proactive and reactive scales displayed divergent patterns of correlation with
      the eight risk/outcome measures. As predicted, the proactive scale corresponded
      with lower criminal risk, older age of first conviction, and decreased odds of
      prior substance misuse and mental illness, whereas the reactive scale
      corresponded with higher criminal risk, earlier age of first conviction, greater
      odds of prior substance misuse and mental illness, and more evidence of
      subsequent arrest. Contrary to predictions, the proactive scale was associated
      with increased rather than decreased commission of disciplinary infractions in
      prison. When participants with elevated proactive scores were compared to
      participants with elevated reactive scores on the eight risk/outcome variables,
      the results revealed that the two profiles were moderately negatively correlated.
      Thus, although proactive criminal thinking is associated with below-average
      criminal risk and below-average future negative outcomes, reactive criminal
      thinking does just the opposite.

PMID- 30239222
TI  - Possible Role of Glymphatic System of the Brain in the Pathogenesis of High
      Altitude Cerebral Edema.
AB  - Simka, Marian, Pawel Latacz, and Joanna Czaja. Possible role of glymphatic system
      of the brain in the pathogenesis of high-altitude cerebral edema. High Alt Med
      Biol 00:000-000, 2018.-In this article, we suggest that the glymphatic system of
      the brain can play an important role in the pathogenesis of high-altitude
      cerebral edema (HACE). Water enters the intercellular space of the brain
      primarily through aquaporin-4 (AQP-4) water channels, the main component of the
      glymphatic system, whereas acetazolamide, pharmacological agent used in the
      prevention of HACE, is the blocker of the AQP-4 molecule. In animal experiments,
      cerebral edema caused by hypobaric hypoxia was associated with an increased
      expression of AQP-4 by astrocytes. Also, the glymphatic system is primarily
      active during sleep, although sleep at high altitude is a well-known risk factor
      of developing HACE. All these findings support our hypothesis. We suggest that
      future research on the prevention and treatment of HACE should involve factors
      that are already known to modify activity of the glymphatic system, such as
      angiotensin-converting enzyme inhibitors or other pharmaceutical agents affecting
      noradrenergic system of the brain, body posture during sleep, anatomy of the
      veins draining the cranial cavity, and the influence of physical activity before
      and during exposure to high altitude, especially in relation to sleep.

PMID- 30239223
TI  - Reliably colonising broiler chickens with Campylobacter spp. using a litter-based
      method.
AB  - 1. Chicken-associated Campylobacter spp. are the cause of most food poisoning
      cases in Europe. In order to study the host-pathogen interactions, a reliable and
      reproducible method of colonising chickens with the bacteria is required. 2. This
      study aimed to identify a more appropriate and less invasive method of
      colonisation (cf. gavaging) by seeding bedding material (litter) that commercial
      chickens are kept on with a mixture of Campylobacter spp., broth and faeces. 3.
      The first phase of the study tested the longevity of Campylobacter spp. recovery
      in seeded litter over 24 h: significantly more Campylobacter spp. was recovered
      at 0 or 3 h post-seeding than at 6 and 24 h post-seeding, indicating that the
      pathogen can survive to detectable levels for at least 3 h in this environment.
      4. In the second phase, three groups of 10 broiler chickens (negative for
      Campylobacter spp. prior to exposure) were exposed at 21 days of age to one of
      three different Campylobacter jejuni and C. coli mixes (A, B, C), using the
      method above. At 28 days of age, birds were euthanised by overdose of barbiturate
      or cervical dislocation, and livers and caeca removed for Campylobacter spp.
      assessment. 5. All liver and 28/30 caeca samples tested positive for
      Campylobacter spp., with mix A and C giving higher counts in the caeca than mix
      B. The method of euthanasia did not affect Campylobacter spp. counts. 6. In
      conclusion, a successful method for reliably colonising broiler chickens with
      Campylobacter spp. has been developed which negates the need for gavaging and is
      more representative of how contamination occurs in the field.

PMID- 30239224
TI  - I Am a Doctor, and Here is My Proof: Chinese Doctors' Identity Constructed on the
      Online Medical Consultation Websites.
AB  - Despite a multitude of previous research focusing on doctors' identities which
      have been constructed through traditional face-to-face communication, their
      identities on online medical consultation websites are still underrepresented in
      research. This paper sketches out how Chinese doctors construct their online
      identities by analyzing 1,000 pieces of conversations between patients and
      doctors retrieved from 120ask.com. The analysis showed that Chinese doctors
      create professional identities online through the use of medical jargon,
      independent vocatives, and diagnostic questioning, while their authoritative
      identity is constructed by using collective vocatives to situate themselves as
      members of hospital communities and using a high modality to carve out their
      authoritative identities. Often Chinese doctors establish their individuality
      through self-reference, and highlight their ordinary side of their identities
      through the use of intimate vocatives and markers of politeness. To some extent,
      this study not only gives comprehensive answers to the research questions but
      also can serve as a facilitator of effective communication and good rapport
      management between doctors and patients in online consultation.

PMID- 30239225
TI  - Defining Glycemic Variability in Very Low-Birthweight Infants: Data from a
      Continuous Glucose Monitoring System.
AB  - BACKGROUND: Glucose variability (GV) is a matter of interest for researches in
      recent years. It is connected with oxidative stress, which is crucial in the
      development of multiple complication of prematurity. However, glycemic
      variability in preterm infants was poorly investigated. This study aims to
      investigate glycemic variability obtained from a continuous glucose monitoring
      (CGM) system in a cohort of very low-birthweight (VLBW) infants. METHODS: A
      prospective, single-center, open cohort study enrolled 74 VLBW infants with a
      mean birthweight of 1066 g and median gestational age of 28 weeks. A CGM system
      (Guardian Real-Time CGM(r), Medtronic, Northridge, CA) was used to measure
      interstitial glucose concentration. The glycemic variability was calculated using
      EasyGV. RESULTS: Most glycemic variability indices in VLBW infants showed log
      normal distribution and for these, geometric mean // * geometric standard
      deviation (GSD) was calculated: M-value 2.28 (// * 1.82), mean amplitude of
      glycemic excursions (MAGE) 1.89 (// * 1.34), average daily risk ratio (ADRR) 2.22
      (// * 2.56), lability index 0.46 (// * 1.71), J-index 0.46 (// * 1.71), low blood
      glucose index 2.05 (// * 1.66), high blood glucose index 1.11 (// * 2.44),
      continuous overlapping net glycemic action (CONGA) 5.54 (// * 1.16), mean of
      daily differences (MODD) 1.23 (// * 1.38), and coefficient of variation 1.15 (//
      * 1.31). Only SD of glucose concentration showed a normal distribution:
      arithmetic mean 1.24 (+/-0.37). ADRR, J-index, MODD, CONGA, and MAGE are
      moderately to strongly correlated with SD. CONCLUSIONS: In our cohort of VLBW
      infants, almost all glycemic variability indices showed skewed positive
      distribution. The natural central tendency measure for the log-normally
      distributed data is the geometric mean and for statistical variation is the GSD.

PMID- 30239226
TI  - Prevalence and Predictors of Obstructive Sleep Apnea in Patients with Chronic
      Obstructive Pulmonary Disease Undergoing Inpatient Pulmonary Rehabilitation.
AB  - The aim of our study was to evaluate the prevalence and predictors of obstructive
      sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD)
      undergoing inpatient pulmonary rehabilitation programs (PRPs). A retrospective
      data review of consecutive stable patients with a known diagnosis of COPD,
      admitted for PRP between January 2007 and December 2013. Full overnight
      polysomnography (PSG) and Epworth Sleepiness Scale (ESS) were assessed in all
      patients. Out of 422 evaluated patients, 190 (45%) showed an Apnea Hypopnea Index
      (AHI) >= 15 events/hour and underwent OSA treatment. Patients with OSA were
      significantly younger and had a less severe airway obstruction as compared to
      patients without OSA. There were no significant differences in cardiac
      comorbidities nor in arterial blood gases. As expected, patients with OSA showed
      significantly more severe diurnal symptoms, as assessed by the ESS and higher
      body mass index (BMI). However, only 69 out of 190 patients with OSA (36.3%)
      showed an ESS >10, whereas 25% of them had BMI <=25 and 41% of them had a BMI
      <30. In all, 68% of patients with OSA were discharged with continuous positive
      airway pressure (CPAP), 15% with Bilevel ventilation, and 17% without any
      ventilatory treatment. In conclusion, in the population studied, the combination
      of OSA and COPD was frequent. BMI and ESS values commonly considered cutoff
      values for the prediction of OSA in the general population may not be accurate in
      a subgroup of patients with COPD.

PMID- 30239227
TI  - Hepatoprotective and antioxidant activities of Annona squamosa seed extract
      against alcohol-induced liver injury in Sprague Dawley rats.
AB  - Alcohol is regarded as the third most common cause of death after hypertension
      and smoking. Its long-term excess exposure leads to alcoholic liver disease (ALD)
      and liver injury, a worldwide health problem without efficient therapy. As there
      is no reliable liver protective drugs in allopathic medical practices, herbs play
      a major role in the management of liver diseases. Thus, the present study was
      designed to evaluate hepatoprotective activity of Annona squamosa seed extract
      against alcohol-induced liver injury in Sprague Dawley rats. Liver toxicity was
      induced by 50% alcohol at dose level of 12 ml/kg po each, for 8 days. Ethanolic
      extract of A. squamosa seed (EEAS) at dose of 200 and 400 mg/kg po were
      administered once daily for 8 consecutive days. The hepatoprotective activity of
      EEAS was assessed in experimental rats using various biochemical parameters like
      ALT, AST, ALP, LDH, SBL, albumin, total cholesterol, and total protein; and
      antioxidant parameters like SOD, CAT, GSH, and TBARS. It demonstrated that the
      treatment with EEAS significantly (p < 0.05-p < 0.001) and dose-dependently
      prevented the alcohol-induced increase in serum levels of hepatic enzymes and
      significantly increased the levels of SOD, CAT, and GSH. It also significantly
      decreased the level of MDA. Histopathology of the liver tissues showed that EEAS
      attenuated the hepatocellular necrosis and led to regeneration and repair of
      cells toward normal. Results of this study strongly indicated the protective
      effect of A. squamosa against alcohol-induced liver injury which may be
      attributed to its hepatoprotective and antioxidant activities.

PMID- 30239228
TI  - The production of wh-questions in Italian-speaking children with SLI.
AB  - We aim at determining whether 7-year-old Italian-speaking children with Specific
      Language Impairment (SLI): (1) have problems with the production of wh-
      questions; (2) display a subject/object asymmetry in producing which- and who
      questions; (3) attempt to simplify questions, especially which- questions; (4)
      have difficulties with movement and verbal agreement in wh- questions. We
      elicited subject and object who and which NP questions in 10 children with SLI (M
      = 7;2), in 10 chronological age (CA)-matched controls (M = 7;2) and 10 language
      matched controls (M = 5;2). Results showed that (1) children with SLI produced
      fewer questions than both control groups; (2) a subject/object asymmetry was
      observed in who questions but not in which NP questions; (3) which NP questions
      were more problematic than who questions; (4) children with SLI produced more
      agreement errors and resorted to simplification strategies to avoid wh- question
      production. Results point to a grammatical deficit due to the computation of
      complex grammatical relations and suggest that there is a misalignment among
      pieces of linguistic competence needed to form Italian wh- questions (wh-
      movement and agreement computation). Outcomes have implications for clinical
      assessment recommending the production of wh- questions to be considered in the
      evaluation of SLI in Italian.

PMID- 30239230
TI  - Response to Burtscher re: "Increased Cytokines at High Altitude: Lack of Effect
      of Ibuprofen on Acute Mountain Sickness, Physiological Variables, or Cytokine
      Levels".

PMID- 30239231
TI  - Extracellular Matrix in Cardiovascular Pathophysiology.
AB  - The extracellular matrix (ECM) actively participates in diverse aspects of
      cardiovascular development and physiology, as well as during disease development
      and progression. ECM roles are determined by its physical and mechanical
      properties and by its capacity to both release bioactive signals and activate
      cell signaling pathways. The ECM serves as a storage depot for a wide variety of
      molecules released in response to injury or with aging. Indeed, there is a
      plethora of examples describing how cells react to or modify ECM stiffness, how
      cells initiate intracellular signaling pathways, and how cells respond to ECM.
      This Perspectives article reviews the contributions of twenty-one articles
      published in The American Journal of Physiology-Heart and Circulatory Physiology
      in response to a call for papers on this topic. Here we summarize the
      contributions of these studies focused on cardiac and vascular ECM. We highlight
      the translational importance of these studies and conclude that the ECM is a
      critical component of both the heart and vasculature. Readers are urged to
      examine and learn from this special call for papers.

PMID- 30239232
TI  - Targeted HFpEF therapy based on matchmaking of human and animal models.
AB  - The diversity in clinical phenotypes and poor understanding of the underlying
      pathophysiology of heart failure with preserved ejection fraction (HFpEF) is the
      main reason why no effective treatments have been found yet. Targeted, instead of
      a one-size-fits-all, treatment seems the only promising approach for treating
      HFpEF. To be able to design a targeted, phenotype-specific HFpEF treatment, the
      matrix relating clinical phenotypes and underlying pathophysiological mechanisms
      has to be clarified. This review discusses the opportunities of additional
      evaluation of the underlying pathophysiological processes, e.g. to evaluate
      biological phenotypes on top of clinical routine, to guide us towards a phenotype
      specific HFpEF treatment. Moreover, a translational approach with matchmaking of
      animal models to biological HFpEF phenotypes will be a valuable step to test the
      effectiveness of novel, targeted interventions in HFpEF.

PMID- 30239233
TI  - Implications for understanding ischemic stroke as a sexually dimorphic disease:
      The role of pial collateral circulations.
AB  - We investigated structural and functional differences in primary and pial
      collateral circulations in adult normotensive male and female Wistar rats. Male
      (n=10) and female (n=7) rats were subjected to middle cerebral artery (MCA)
      occlusion and changes in relative cerebral blood flow (rCBF) in MCA and pial
      collateral territories were measured by multi-site laser Doppler flowmetry. Rats
      were then transcardially perfused with a mixture of carbon black and latex,
      perfusion fixed and imaged to compare primary and pial collateral structure
      between males (n=4) and females (n=3), including lumen diameters and number. To
      study pial collateral function, leptomeningeal anastomoses (LMAs) were isolated
      and pressurized from male (n=7) and female (n=6) rats. Myogenic tone and
      reactivity to pressure, vascular function to pharmacological activator or
      inhibitor of ion channels were measured and compared. There was no difference
      between rCBF in both MCA and pial collateral territories during occlusion and
      reperfusion between groups. Compared with LMAs from males, female LMAs had
      similar myogenic tone (24.0+/-7.3 vs. 16.0+/-3.7%; P>0.05) and reactivity to
      increased pressure, and similar vascular responses to vasoconstrictive and
      vasodilatory stimuli. Additionally, compared with females, LMAs from males had
      similar number (21+/-1 vs. 20+/-2; P>0.05) and diameter (30.5+/-2.0 MUm vs.
      26.2+/-0.6 MUm; P>0.05), and no sex difference was detected in the diameter of
      arterial segments of circle of Willis. Together, our data establish no sex
      difference of cerebral collateral structure or function, suggesting that the
      reduced severity of stroke outcome in female rats is not likely due to
      differences in the cerebral collateral circulation.

PMID- 30239234
TI  - High Fat Diet Induced Hypertension is Associated with a Pro-Inflammatory T Cell
      Profile in Male and Female Dahl Salt Sensitive Rats.
AB  - Evidence supports a sex difference in the impact of a high fat diet (HFD) on
      cardiovascular outcomes, with male experimental animals exhibiting greater
      increases in blood pressure (BP) than females. The immune system has been
      implicated in HFD-induced increases in BP, and there is a sex difference in T
      cell activation in hypertension. The goal of this study was to determine the
      impact of HFD on BP, aortic and renal T cell profiles in male and female Dahl
      salt-sensitive rats (DSS). We hypothesize that male DSS will have greater
      increases in BP and T cells with a HFD compared to females. BP was measured by
      tail-cuff plethysmography, and aortic and renal T cells were assessed by flow
      cytomety in male and female DSS on a normal fat diet (NFD) or HFD from 12 to 16
      weeks of age. A HFD increased BP in male and female DSS to a similar degree.
      Increases in BP were accompanied by increased percentages of CD4+ T cells and
      Th17 cells in both sexes, although males have more pro-inflammatory T cells.
      Percentages of renal CD3+ and CD4+ T cells and Th17 cells were increased in both
      sexes by a HFD, although the increase in CD3+ T cells was greater in males. HFD
      decreased the percentage of aortic and renal Tregs in both sexes, although
      females maintained more Tregs than males regardless of diet. In conclusion, both
      male and female DSS exhibit BP sensitivity to a HFD.

PMID- 30239235
TI  - Pathophysiology, adaptation and imaging of the right ventricle in the Fontan
      circulation.
AB  - The Fontan procedure, which creates a total cavo-pulmonary anastomosis and
      represents the final stage of palliation for hypoplastic left heart syndrome
      (HLHS), generates a unique circulation relying on a functionally single right
      ventricle (RV). The RV pumps blood in series around the systemic and pulmonary
      circulation, which requires adaptation to the abnormal volume and pressure loads.
      We provide a complete review of the RV adaptations as it assumes the role of the
      systemic ventricle, the progression of RV dysfunction to a distinct pattern of
      heart failure unique to this disease process, and the assessment and management
      strategies employed in order to protect and rehabilitate the failing RV of Fontan
      circulation.

PMID- 30239236
TI  - Direct Engagement of TLR9 Ligand with T Helper Cells Leads to Cell Proliferation
      & Up-regulation of Cytokines.
AB  - PURPOSE: Toll like receptor (TLR) engagement is primarily a function of the
      innate immune cells. The purpose of the study was to assess direct uptake of ODN
      2216 in T helper cells and effects on cell proliferation and cytokine expression.
      METHODS: We isolated CD4+ CD25- T helper cells by magnetic sorting and studied
      the uptake of ODN 2216 using flow cytometry and confocal microscopy. We then
      studied the effect of ODN 2216 engagement on cell proliferation and cytokine
      expression using flow cytometry and gene expression of TLR9 signaling genes using
      real time RT-PCR. RESULTS: We made a chance observation that purified T helper
      cells from healthy individuals consistently bind to the TLR9 ligand ODN 2216. In
      PBMCs, on the other hand, 98% of monocytes preferentially bound to ODN 2216 FITC,
      indicating that they competed with the lymphocytes. We confirmed intracellular
      localization of ODN 2216 FITC as well as intracellular expression of TLR9 in
      Thelper cells. Furthermore, ODN 2216 FITC was also co-localized with the
      lysosomal membrane associated protein 1. The uptake of TLR9 ligand culminated in
      cellular proliferation, up-regulation of cytokines and increased mRNA expression
      of TLR9 and IRF7 in T helper cells, in the absence of antigen presenting cells.
      ODN 2216 uptake was inhibited by promethazine as well as by TLR9 antagonist.
      CONCLUSIONS: Our results show a direct engagement of TLR9 ligand in T helper
      cells and suggest involvement of TLR9 signalling in CD4+T cells, which may
      envisage novel targets for TLR inhibitors.

PMID- 30239237
TI  - Bibliometric profile of global scientific research on digoxin toxicity (1849
      2015).
AB  - Digoxin is a cardiac glycoside derived from the common foxglove digitalis
      purpurea and has been available for several centuries as a medicinal agent.
      Despite extensive patient experience over many years, there remains some
      controversy regarding the possibility that digoxin might have a deleterious
      effect on survival. This study was constructed to assess trends in digoxin
      toxicity research using well-established qualitative and quantitative
      bibliometric indicators. The current study is based on publications that have
      been indexed in Scopus. Articles referring to the subject of digoxin toxicity
      between 1849 and 2015 were assessed according to the document type, publication
      language, countries/territories, institutions, journal, impact factors, total
      number of citations, h-index, average number of citations per publication, and
      international collaborations. There were 2900 publications that included 2542
      (87.7%) original research articles, while 5.3% were reviews and 4.6% letters. The
      country of origin was the USA in 849 publications, Germany in 241, the UK in 150,
      and France in 143. The USA and the UK had the highest number of international
      collaborations. The average number of citations per publications related to
      digoxin toxicity was 8.1, and the h-index was 59. The USA and Canada had the
      highest h-indices by country at 46 and 22, respectively. This study presents the
      first bibliometric analysis on digoxin toxicity publications. The USA was the
      most important contributors to digoxin toxicity literature with the greatest
      international collaboration, largest number of articles and highest h-index,
      followed by Germany and the UK. There has been a trend towards reduced
      publication numbers related to digoxin toxicity at global level, although it is
      still an important issue and we present the current research themes related to
      digoxin toxicity that were identified.

PMID- 30239239
TI  - Efficacy of Intravitreal Dexamethasone Implant in Patients of Uveitis Undergoing
      Cataract Surgery.
AB  - PURPOSE: To assess postoperative inflammation using laser flare photometer,
      following phacoemulsification with or without single intraoperative intravitreal
      dexamethasone implant in addition to standard of care, in patients of uveitis
      with cataract. METHODS: Prospectively, 30 eyes with uveitic cataract were
      randomized into 2 groups (i) standard of care (SOC group) (ii) Dexamethasone
      implant (DEXA group). Both the groups underwent phacoemulsification with
      intraocular lens implantation and standard of care treatment for uveitis, but
      DEXA group additionally received intraoperative intravitreal dexamethasone
      implant. Patients were followed at least till 6 months. RESULTS: DEXA group had
      significantly less postoperative flare (LFP values) (P<0.05) as compared to SOC
      group and also recovery of flare to preoperative value occurred much early in
      DEXA group. 37.5% cases developed CME in SOC group but none in DEXA group. Mean
      CMT (267.81+/-34.26MUm) and final logMar BCVA (0.036+/-0.063) was significantly
      better in DEXA group (p<0.04). CONCLUSIONS: Intraoperative intravitreal
      dexamethasone implant is a safe and effective option for preventing and managing
      the postoperative inflammation in uveitic cataract.

PMID- 30239238
TI  - The Effect of China's National Essential Medicine Policy on Health Expenses:
      Evidence From a National Study.
AB  - To increase use of medical service across the country, the Chinese government has
      tried to improve equity in health care access and reduce patients' medical
      expenses. For this purpose, the National Essential Medicine Policy (NEMP) was
      introduced in 2009 to mandate the distribution of medicines to health care
      facilities at a low cost and without profit. This study aims to evaluate the
      effect of the essential medicine policy on average per-visit expenses for
      outpatient and inpatient services. The annual national surveillance system data
      covering all the grassroots-level primary health care facilities (PHFs) in 2675
      counties and 31 provinces in China during 2008 to 2012 were used in this study.
      The 4-level hierarchical random effects models were utilized to deal with
      possible dose-response effects of the policy and possible variations of such
      effects at the provincial, county, and facility levels. Our research findings
      suggest that the NEMP had positive effects in reducing both outpatient and
      inpatient expenses at grassroots level, and the policy effects tended to be
      greater as the exposure time increased. This study provides implications on
      reforming China's health system and its medicine cost control policies.

PMID- 30239240
TI  - Information Communication Technologies and Intimate Partner Violence in China.
AB  - Although a substantial number of studies have investigated factors that
      influenced intimate partner violence (IPV), very few have assessed the connection
      between the use of information and communication technology (ICT) and such
      violence. Using survey data collected from over 400 women in a large Chinese
      city, this study explored how the involvement of various ICT-related activities
      affects Chinese women's experiences with psychological, physical, and sexual
      abuse. We found that some forms of media usage and online activities, such as
      times spent on paper books and Internet and browsing entertainment and sports
      news as well as watching movies and TVs online, were linked to a higher or lower
      likelihood of being a victim of IPV. Feelings of loneliness and helplessness were
      associated with more IPV victimization experiences. Married women were less
      likely to experience IPV, whereas working women were subject to greater IPV.

PMID- 30239241
TI  - Individual Differences in Executive Function: The Role of Parental Monitoring as
      a Moderator.
AB  - OBJECTIVE: Parental monitoring is a factor which affects verbal and nonverbal
      inhibition components of children's executive functions.,. METHOD: 112 sixth
      grade Kurdish children (mean age: 11 years 5 months) participated in the study.
      Children were matched on level of hyperactivity. Parents completed the Parental
      Monitoring Assessment (PMA) and the Strengths and Difficulties Questionnaire
      (SDQ). Children completed theStop-Signal task, Modified Opposite Worlds and a
      challenging star puzzle in order to assess executive function components. PROCESS
      analysis was also used to perform the moderation analysis. RESULTS: Children
      characterized by poor parental monitoring had deficits in inhibitory control and
      had significantly slower processing speeds and made significantly more errors
      than their matched controls. Furthermore, children with high levels of
      hyperactivity had difficulties in inhibitory control, accuracy, processing speed,
      and task persistence compared with the control group.Contrary to our prediction,
      there were no significant differences in reaction times compared with the control
      group. PROCESS analysis showed a significant moderating role of parental
      monitoring in the association between each of accuracy, verbal inhibition, and
      task persistence with hyperactivity. CONCLUSION: the current study suggests that,
      similar to hyperactivity, children with poor parental monitoring appear to have
      difficulties in executive function.

PMID- 30239242
TI  - Empirical Research on Domestic Violence in Contemporary China: Continuity and
      Advances.
AB  - Domestic violence is not uncommon in China. Myths and misconceptions about it do
      exist, especially in the context of rapid social changes. Compared with its
      Western counterparts, the study on domestic violence in China is considered
      rudimentary and of low priority. Empirical studies, especially those measuring
      the correlates and/or risk factors related to domestic violence, are still
      lacking. This special issue aims to advance understanding on domestic violence
      through much-needed empirical research. It also demonstrates joint efforts by
      local Chinese scholars and their Western counterparts to strengthen collaboration
      in this important research area. Based on relatively large sample surveys, the
      articles incorporated in this special issue provide relatively accurate estimates
      of factors related to domestic violence and responses to it in mainland China and
      Taiwan. Future studies should give priority to developing indigenous theories and
      practices in addition to adapting and testing theories and models developed in
      the West.

PMID- 30239243
TI  - The Effect of a Resilience Enhancement Programme for Female Runaway Youths: A
      Quasi-Experimental Study.
AB  - The effects of a resilience enhancement programme on resilience, depression,
      anxiety, and problem drinking among female runaway youths living in shelters were
      evaluated. Participants were 32 youths (16 experimental and 16 control
      participants), assessed at pre-test, post-test, and one-month follow-up. The
      programme incorporated five protective factors associated with resilience: self
      esteem, self-regulation, relational skills, problem-solving skills, and goal
      setting skills. There were significant group-by-time interaction effects for
      resilience, anxiety, and problem drinking at one-month follow-up. The preliminary
      results suggest that providing female runaway youths with this programme focusing
      on protective factors may enhance resilience and mitigate anxiety, and problem
      drinking.

PMID- 30239244
TI  - Need to Prioritize Education of the Public Regarding Stroke Symptoms and Faster
      Activation of the 9-1-1 System: Findings from the Florida-Puerto Rico CReSD
      Stroke Registry.
AB  - OBJECTIVE: Demographic differences (race/ethnicity/sex) in 9-1-1 emergency
      medical services (EMS) access and utilization have been reported for various time
      dependent critical illnesses along with associated outcome disparities. However,
      data are lacking with respect to measuring the various components of time taken
      to reach definitive care facilities following the onset of acute stroke symptoms
      (i.e., stroke onset to 9-1-1 call, EMS response, time on-scene, transport
      interval) and particularly with respect to any differences across ethnicities and
      sex. Therefore, the specific aim of this study was to measure the various time
      intervals elapsing following the first symptom onset (FSO) from an acute stroke
      until stroke hospital arrival (SHA) and to delineate any race/ethnic/sex-related
      differences among any of those measurements. METHODS: The Florida-Puerto Rico
      Stroke Registry (FLPRSR) is an on-going, voluntary stroke registry of hospitals
      participating in the Get with the Guidelines-Stroke initiative. The study
      population included patients treated at Florida hospitals participating in the
      FLPRSR between 2010 and 2014 who had called 9-1-1 and were managed and
      transported by EMS. In total, 10,481 patients (16% black, 8% Hispanic, 74% white)
      had complete data-sets that included birthdate/year, sex, ethnic background,
      date/hour/minute of FSO and date/hour/minute of EMS response, scene arrival, and
      SHA. RESULTS: Median time from FSO to SHA was 339 minutes (interquartile range
      [IQR] of 284-442), 301 of which constituted the time elapsed from FSO to the 9-1
      1 call (IQR =249-392) versus only 10 from 9-1-1 call to EMS arrival (IQR =7-14),
      14 on-scene (IQR =11-18) and 12 for transport to SHA (IQR =8-19). The FSO to 9-1
      1 call interval, being by far the longest interval, was longest among whites and
      blacks (302 minutes for both) versus 291 for Hispanics (p = 0.01). However, this
      11-minute difference was not deemed clinically-significant. There were neither
      significant sex-related differences nor any racial/ethnic/sex differences in the
      relatively short EMS-related intervals. CONCLUSIONS: Following acute stroke
      onset, time elapsed for EMS response and transport is relatively short compared
      to the lengthy intervals elapsing between symptom onset and 9-1-1 system
      activation, regardless of demographics. Exploration of innovative strategies to
      improve public education regarding stroke symptoms and immediate 9-1-1 system
      activation are strongly recommended.

PMID- 30239245
TI  - Ocular Exposures Reported to United States Poison Control Centers.
AB  - PURPOSE: To investigate the epidemiology of ocular exposures reported to poison
      control centers in the United States. METHODS: A retrospective analysis of ocular
      exposures from 2000 to 2016 was conducted using National Poison Data System data.
      RESULTS: United States poison control centers received 1,436,683 reports of
      ocular exposures during 2000-2016, averaging 7,043 exposures per month. The
      annual frequency of ocular exposures declined significantly by 37.2% from 2006 to
      2016. The ocular exposure rate per 10,000 US residents was highest among children
      < 6 years of age (10.7), particularly among 2-year-olds (20.5), and was lowest
      among adults >= 20 years of age (1.9). The majority of the exposures resulted in
      minor effects (51.4%). Among exposed individuals, 23.0% were treated and released
      and 0.3% were admitted to a healthcare facility. Household cleaning products
      (22.2%), cosmetics/personal care products (15.7%), and pesticides (7.4%) were the
      most common substance categories associated with exposures, but exposures to
      building and construction products (18.1%), industrial cleaners (14.9%), and
      chemicals (14.1%) resulted in a higher percentage of moderate or major effects.
      In addition, exposures to alkaline substances had a higher percentage of moderate
      or major effects. CONCLUSION: Although the annual frequency of ocular exposures
      declined during the last decade, the number of exposures remains high,
      particularly among young children. The commonly associated substance categories
      identified in this study represent important preventable sources of morbidity.

PMID- 30239246
TI  - Untargeted metabolomics: an overview of its usefulness and future potential in
      prenatal diagnosis.
AB  - INTRODUCTION: Metabolomics opens up new avenues for biomarker discovery in
      different branches of medicine, including perinatology. Chromosomal aberration,
      preterm delivery (PTD), congenital heart defects, spina bifida, chorioamnionitis,
      and low birth weight are the main perinatal pathologies. Investigations using
      untargeted metabolomics have found the candidate metabolites for diagnostic
      biomarkers. Areas covered: This review describes areas of prenatal diagnosis in
      which untargeted metabolomics has been used. Data on the disease, type of sample,
      techniques used, number of samples used in the study, and metabolites obtained
      including the sign of their regulation are summarized. Expert commentary:
      Untargeted metabolomics is a powerful tool which can shed a new light on prenatal
      diagnostics. It helps to discover affected metabolic pathways what may help to
      reveal disease pathogenesis and propose potential biomarkers. Among others,
      glycerol and 2- and 3-hydroxybutyrate were proposed as markers of chromosomal
      aberration. Serum metabolic signature of PTD was characterized by increased
      lipids and decreased levels of hypoxanthine, tryptophane, and pyroglutamic acid.
      Lower level lipids and vitamin D3 metabolites together with increased bilirubin
      level in maternal serum were associated with macrosomia. However, to give a real
      value to those assays and allow their clinical application multicenter, large
      cohort validation studies are necessary.

PMID- 30239248
TI  - Gender Differences in Perceived Workplace Flexibility Among Older Workers in the
      Netherlands: A Brief Report.
AB  - Flexibility in work schedule and work location have been suggested as being work
      features that may promote prolonged employment among older workers. This study
      focuses on the question whether access to workplace flexibility differs between
      male and female older workers and how potential differences can be explained.
      Analyses are based on data collected in 2015 among 4,813 Dutch older workers (age
      60-65 years), who were employed in the government, education, care, and welfare
      sectors. Results show that the studied women on average perceive to have less
      workplace flexibility than men, both in work schedule and in work location. The
      gender difference in perceived location flexibility can be fully explained by
      differences in the human capital and job characteristics of male and female older
      workers. The gender difference in perceived schedule flexibility can be captured
      less clearly by these factors. This disadvantaged position of late-career women
      warrants attention in discussions about prolonged employment.

PMID- 30239247
TI  - Therapeutic potential of oxazole scaffold: a patent review (2006-2017).
AB  - INTRODUCTION: Oxazoles are oxygen and nitrogen containing five membered
      heterocyclic ring systems that are present in various anticancer, antimicrobial,
      antihyperglycemic, anti-inflammatory agents etc. of natural origin. These
      pharmacologically active oxazole derivatives have attracted numerous researchers
      to explore this scaffold for the design and development of newer potential
      therapeutic agents. A large number of synthetic oxazole containing molecules have
      been reported over the period that exhibited wide spectrum of pharmacological
      profiles. Some of them have shown promising therapeutic potential and have
      qualified for both preclinical and clinical evaluations. Areas covered: In this
      review, the patents (published during 2006-2017) focusing on the biological
      potential of oxazoles have been covered. Therapeutic applications and various
      techniques/assays employed for the in vitro/in vivo evaluation of patented
      derivatives have been discussed majorly. Expert opinion: Chemically oxazole
      offers three positions for substitution. These substituted oxazole derivatives of
      natural as well as synthetic origin have numerous pharmacological applications
      including anticancer, anti-Alzheimer's, anti-hyperglycemic, anti-inflammatory,
      antibacterial etc. Their pharmacological actions are mainly mediated through
      enzyme/receptor involved in the particular disease. The flexible nature of this
      ligand for various molecular level targets (enzyme/receptor) make this
      heterocylce an attractive scaffold for development of effective and clinically
      relevant oxazole containing therapeutic agents.

PMID- 30239249
TI  - Survival of children with a Wilms tumor in Blantyre, Malawi.
AB  - Wilms tumor (WT) has a survival rate above 90% in high income countries. Reported
      survival rates in sub-Saharan Africa are much lower and long-term outcome is not
      well known as follow-up is challenging. In Blantyre, Malawi, an adapted WT
      treatment guideline with preoperative chemotherapy, supportive care, and
      strategies to enable children and parents to complete treatment was introduced in
      2006. Between 2006 and 2011, 73 children with a unilateral WT were treated.
      Follow-up, including home visits when needed, was done. Median follow-up time is
      5 years (range 14-95 months). Two and five-year event free survivals are 46 and
      42%. Causes of treatment failure are: 7% (5/73) abandonment of treatment, 15%
      (11/73) death during treatment and 30% (22/73) disease-related deaths (persistent
      disease and relapse). Long-term follow-up is challenging but necessary to be able
      to assess outcome and the true impact of interventions.

PMID- 30239250
TI  - Weight Reduction Goal Achievement Among Veterans With Mental Health Diagnoses
      [Formula: see text].
AB  - BACKGROUND: Despite the use of weight management programs among veterans, the
      impact of mental health diagnoses on weight reduction goal achievement is
      unknown. AIMS: We aimed to describe the prevalence and association of mental
      health diagnoses with a 5% weight reduction goal achievement. METHODS: Logistic
      regression was used to describe the association between mental health diagnoses
      and weight reduction goal achievement at 6, 12, and 24 months among 402 veterans
      enrolled in a weight management program. RESULTS: More than 43% of veterans had a
      mental health diagnoses, with depressive disorders, posttraumatic stress disorder
      (PTSD), and substance use disorders being the most prevalent. At all three times,
      simply having a mental health diagnosis was not associated with weight reduction
      goal achievement. Specific diagnoses were associated with a greater likelihood of
      achieving weight reduction goals at 12 months (PTSD and Drug Use Disorder) and 24
      months (Anxiety Disorder and Other Mental Health Diagnosis). CONCLUSION: The
      findings suggest that unhealthy weight is quite common for individuals with
      mental health diagnoses; however, weight reduction goal achievement may be
      equally likely for those with and without mental health diagnoses. The prevalence
      of mental health diagnoses among veterans seeking weight reduction suggests that
      psychiatric nurses should be aware of this common comorbidity.

PMID- 30239251
TI  - The Effects of Domestic Violence on Violent Prison Misconduct, Health Status, and
      Need for Post-Release Assistance Among Female Drug Offenders in Taiwan.
AB  - Although much research has documented the fact that a high percentage of female
      inmates serving sentences for drug offenses have experienced domestic violence
      prior to incarceration, little research has been done to explore the potential
      long-term impact of domestic violence on prison misconduct, health status, and
      the need for post-release assistance. Based on survey data for 633 female drug
      offenders collected from Taiwanese correctional facilities in 2014, about one
      third (32%) of the offenders reported experienced domestic violence at least once
      prior to their incarceration. In all, 27% of them experienced being violently
      abused by a spouse/coinhabitant. Multivariate regression analyses indicate that a
      prior history of domestic violence victimization contributes significantly to
      inmates' violent misconduct even after controlling for a set of potential
      intervening variables. In addition, female drug offenders who were the victims of
      domestic violence reported higher levels of health problems in the prison
      setting, and perceived need for greater after-release assistance.

PMID- 30239252
TI  - High-Dose Vincristine Sulfate Liposome Injection, for Advanced, Relapsed, or
      Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in an
      Adolescent and Young Adult Subgroup of a Phase 2 Clinical Trial.
AB  - PURPOSE: A study of vincristine sulfate (VCR) liposome injection (VSLI) was
      conducted in patients with advanced, relapsed, or refractory, Philadelphia
      chromosome-negative acute lymphoblastic/lymphocytic leukemia (ALL). A
      retrospective subgroup analysis of the results was performed to evaluate the
      safety and efficacy of VSLI in the adolescent and young adult (AYA) patients.
      METHODS: Of the 65 patients treated in the pivotal Phase 2 Study HBS407
      (NCT00495079), 44 patients were aged <=39 years (median 27 [range 19-39] years)
      and were included in this analysis. Patients received VSLI (2.25 mg/m2
      intravenously every 7 +/- 3 days) without dose capping or concurrent steroid
      administration in continuous 28-day cycles. RESULTS: VSLI was well tolerated in
      the AYA patients over a median of 5 (range 1-15) doses administered. One-third of
      patients (36%) experienced treatment-related serious adverse events (AEs) with
      peripheral neuropathy (7%), tumor lysis syndrome (7%), and febrile neutropenia
      (5%) in >1 patient. Neuropathy-associated AEs occurred in 82% patients; no
      neuropathy-related deaths occurred. The rate of complete remission (CR) (with or
      without complete blood count recovery) by investigator assessment was 25% in AYA
      patients, and the overall response rate was 39%. Median leukemia-free survival in
      AYA patients attaining CR was 135 (range 32-463) days, and median overall
      survival was 141 (range 13-620) days. CONCLUSION: VSLI provided a meaningful
      clinical benefit to AYA patients with ALL, and its safety profile was comparable
      to that of VCR despite the delivery of higher doses (individual and cumulative).

PMID- 30239253
TI  - Long-Term Care for Older Adults in ASEAN Plus Three: The Roles of Family,
      Community, and the State in Addressing Unmet Eldercare Needs.
AB  - OBJECTIVE: To introduce this Special Issue that focuses on understanding the
      issues surrounding the long-term care (LTC) in selected societies in Southeast
      and East Asian countries. METHOD: We first provide demographic and socioeconomic
      context for these countries and then summarize the seven articles in this issue.
      RESULTS: The articles highlight the rapidly rising demand for LTC in this region
      in the next few decades given the declining fertility, lengthening life
      expectancy, and increasing migration. They also discuss challenges and strategies
      in meeting these demands. Most countries are ill prepared to cope with the demand
      for LTC with older adults heavily rely upon female family members for care.
      Elderly women in low-income households have the greatest unmet need. DISCUSSION:
      Home-based and community-based services are set to become an integral part of the
      LTC system. It is important to incorporate older adults' cultural norms and
      wishes in their care plan and provision.

PMID- 30239254
TI  - A novel p.Gly187Arg TP53 variant appears to result in Li-Fraumeni syndrome.
AB  - Li-Fraumeni syndrome is an autosomal dominant cancer syndrome characterized by
      pathogenic variants in the TP53 gene on chromosome 17. The most common cancers in
      Li-Fraumeni kindreds include sarcomas, breast cancer, brain tumors, and
      adrenocortical carcinoma. We report a 9-month-old male who was diagnosed with an
      adrenocortical tumor and later found to harbor a novel TP53 c.559 G > C germline
      variant, resulting in p.Gly187Arg. Family history included early-onset breast
      cancer in his paternal grandmother and paternal great-grandfather, as well as
      colon cancer at age 31 in a paternal cousin. The same TP53 variant was later
      confirmed in his paternal grandmother. Based on this information, his father (age
      28, obligate carrier for the variant) was referred for colonoscopic screening and
      found to have multiple adenomatous polyps. This previously undescribed variant
      lies at an exon/intron boundary and is predicted to decrease splice site
      efficiency with resulting altered splicing or exon skipping. Our patient's family
      history provides limited evidence that this variant is a cause of Li-Fraumeni
      syndrome.

PMID- 30239255
TI  - Liposome: composition, characterisation, preparation, and recent innovation in
      clinical applications.
AB  - In the last decades, pharmaceutical interested researches aimed to develop novel
      and innovative drug delivery techniques in the medical and pharmaceutical fields.
      Recently, phospholipid vesicles (Liposomes) are the most known versatile
      assemblies in the drug delivery systems. The discovery of liposomes arises from
      self-forming enclosed phospholipid bilayer upon coming in contact with the
      aqueous solution. Liposomes are uni or multilamellar vesicles consisting of
      phospholipids produced naturally or synthetically, which are readily non-toxic,
      biodegradable, and are readily produced on a large scale. Various phospholipids,
      for instance, soybean, egg yolk, synthetic, and hydrogenated phosphatidylcholine
      consider the most popular types used in different kinds of formulations. This
      review summarises liposomes composition, characterisation, methods of
      preparation, and their applications in different medical fields including cancer
      therapy, vaccine, ocular delivery, wound healing, and some dermatological
      applications.

PMID- 30239256
TI  - Assistive technology applications for students with reading difficulties: special
      education teachers' experiences and perceptions.
AB  - PURPOSE: Reading and writing applications (with text-to-speech, TTS and speech-to
      text, STT functions), used as assistive technology (AT) for students with reading
      difficulties are increasingly used in education, however, research has not
      sufficiently enough evaluated its potential. The purpose of this study was to
      explore how assistive reading and writing applications were perceived to function
      with regard to students' possibilities to assimilate (i.e., "read") and
      communicate (i.e., "write") text. METHODS: Following a six-week app intervention,
      this follow-up survey contained 54 special education teachers' perceptions of how
      the use of apps impacted student motivation, learning, and its usability in
      special education. A total of 59 students with reading difficulties from Grade 4,
      Grade 8 and from high school, were assessed. Analyses included quantitative and
      qualitative analyses of teachers' responses and written material. RESULTS: The
      results showed individual differences in how teachers perceived app usage for
      text-interaction purposes, including how app usage affected student motivation
      and autonomy for text-based learning. Eighty-two per cent of the younger and
      forty-seven per cent of older students continued to use the technology after the
      intervention, but in various degrees. CONCLUSIONS: Based on these findings,
      students with reading difficulties seem to be able to use AT in order to
      assimilate text (i.e., to read) and to communicate text (i.e., to write), and,
      thus, AT has the potential to promote participation in regular education. Future
      research should focus on how to customize assistive technology support in order
      to better utilize the potential. Implication for rehabilitation This study found
      that students with reading difficulties could use reading and writing apps (with
      text-to-speech, TTS and speech-to-text, STT) in portable tables to be able to
      gain access to, and to produce text in an applied school setting. To use TTS and
      STT as assistive technology efficiently may require relative extensive support
      and training, but even with this support, not all students in this study
      benefited from the potential use of the technology, as the processes of being
      able to gain access to and to produce text with assistive technology seem to be a
      difficult process for some of the students. It is proposed that in order to
      enable all students with reading difficulties possibilities to use assistive
      technology efficiently, its uses need to be customized even further than was done
      in this extensive intervention.

PMID- 30239257
TI  - Intestinal microorganisms involved in colorectal cancer complicated with
      dyslipidosis.
AB  - BACKGROUND: Abnormal lipid metabolism is considered to be one of main promoters
      of colorectal cancer (CRC), and intestinal microorganisms may be involved in CRC
      in patients with abnormal lipid metabolism. OBJECTIVE: To investigate lipid
      metabolism in CRC patients and explore the role of intestinal microorganisms in
      CRC complicated with abnormal lipid metabolism. METHODS: Overall, 150 CRC
      patients in Huzhou Central Hospital from January 2016 to September 2017 were
      recruited in the present study. Basic patient information and clinical
      serological indicators were investigated and analyzed. Twenty-one stool samples
      were collected from patients after receiving informed consent. Next-generation
      sequencing technology was used to sequence bacterial 16S ribosomal RNA.
      Bioinformatics analysis was used to profile the microbial composition and screen
      distinctive bacteria in patients with CRC complicated with abnormal lipid
      metabolism. RESULTS: Apo B and FFA levels were higher in patients with stage I
      disease than in patients with other stages. HDL, LDL, Apo B and FFA levels were
      higher in female patients than in male patients. FFA level was higher in rectal
      cancer patients than in colon cancer patients. These differences were
      statistically significant (p < 0.05). The proportion of Escherichia/Shigella was
      increased in CRC patients with hyperlipoidaemia and hypercholesteremia; the
      abundance of Streptococcus was increased in CRC patients with hyperlipoidaemia;
      the abundance of Clostridium XIVa was reduced in CRC patients with
      hyperlipoidaemia and hypercholesteremia; and the abundance of Ruminococcaceae was
      reduced in CRC patients with hypercholesteremia. Bilophila and Butyricicoccus
      were closely related to CRC patients without hyperlipoidaemia or
      hypercholesteremia, and Selenomonas, Clostridium, Bacteroidetes Slackia,
      Burkholderiales and Veillonellaceae were closely related to CRC patients with
      hyperlipoidaemia. Some pathways, including secretion system, chaperones and
      folding catalysts, amino sugar and nucleotide sugar metabolism, arginine and
      proline metabolism, glycine, serine and threonine metabolism, histidine
      metabolism, pores and ion channels, nitrogen metabolism and sporulation, may be
      involved in lipid metabolism abnormality in CRC patients. CONCLUSIONS: Many CRC
      patients have abnormal lipid metabolism, and the intestinal microbiota is altered
      in these CRC patients.

PMID- 30239259
TI  - The predictive capacity of self-reported motivation vs. early observed
      motivational language in cognitive behavioural therapy for generalized anxiety
      disorder.
AB  - Client motivation to change is often considered a key factor in psychotherapy. To
      date, research on this client construct has largely relied on self-report, which
      is prone to response bias and ceiling effects. Moreover, self-reported motivation
      has been inconsistently related to treatment outcome. Early observed client in
      session language may be a more valid measure of initial motivation and thus a
      promising predictor of outcome. The predictive ability of motivational factors
      has been examined in addiction treatment but has been limited in other
      populations. Addressing this lack, the present study investigated 85 clients
      undergoing cognitive behavioural therapy (CBT) alone and CBT infused with
      motivational interviewing (MI-CBT) for severe generalized anxiety disorder. There
      were two aims: (1) to compare the predictive capacity of motivational language
      vs. two self-report measures of motivation on worry reduction and (2) to examine
      the influence of treatment condition on motivational language. Findings indicated
      that motivational language explained up to 35% of outcome variance, event 1-year
      post-treatment. Self-reported motivation did not predict treatment outcome.
      Moreover, MI-CBT was associated with a significant decrease in the most
      detrimental type of motivational language compared to CBT alone. These findings
      support the importance of attending to in-session motivational language in CBT
      and learning to respond to these markers using motivational interviewing.

PMID- 30239258
TI  - Lesional and perilesional tissue characterization by automated image processing
      in a novel gyrencephalic animal model of peracute intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is an important stroke subtype, but preclinical
      research is limited by a lack of translational animal models. Large animal models
      are useful to comparatively investigate key pathophysiological parameters in
      human ICH. To (i) establish an acute model of moderate ICH in adult sheep and
      (ii) an advanced neuroimage processing pipeline for automatic brain tissue and
      hemorrhagic lesion determination; 14 adult sheep were assigned for
      stereotactically induced ICH into cerebral white matter under physiological
      monitoring. Six hours after ICH neuroimaging using 1.5T MRI including structural
      as well as perfusion and diffusion, weighted imaging was performed before
      scarification and subsequent neuropathological investigation including
      immunohistological staining. Controlled, stereotactic application of autologous
      blood caused a space-occupying intracerebral hematoma of moderate severity,
      predominantly affecting white matter at 5 h post-injection. Neuroimage post
      processing including lesion probability maps enabled automatic quantification of
      structural alterations including perilesional diffusion and perfusion
      restrictions. Neuropathological and immunohistological investigation confirmed
      perilesional vacuolation, axonal damage, and perivascular blood as seen after
      human ICH. The model and imaging platform reflects key aspects of human ICH and
      enables future translational research on hematoma expansion/evacuation, white
      matter changes, hematoma evacuation, and other aspects.

PMID- 30239260
TI  - Mock Jurors' Perceptions of Sexual Assault on a University Campus.
AB  - The purpose of this study was to examine how defendant gender, victim gender,
      location of sexual assault (professor's office vs. fraternity party), and whether
      the defendant was intoxicated influenced mock jurors' decisions in a sexual
      assault case. Mock jurors ( N = 503) read a mock trial transcript depicting an
      alleged sexual assault and were asked to render a dichotomous verdict, continuous
      guilt rating, and rate their perceptions of the victim and defendant. There was
      no influence on mock jurors' dichotomous verdicts. However, the presence of
      intoxication did influence continuous guilt ratings; intoxicated defendants
      elicited higher guilt ratings compared to sober defendants. Whether the defendant
      was intoxicated and the location of the crime were found to impact mock jurors'
      perceptions of the defendant (e.g., believability, credibility); whereas the
      gender of the defendant affected the perceived control the defendant had over the
      situation. Victim gender was found to impact mock jurors perceptions of the
      victim, such that female victims were perceived more favorably than male victims;
      this may support the idea that male victims of sexual assault are generally
      perceived more negatively than female victims. These results, and more, are
      discussed in terms of the current study and the larger implications.

PMID- 30239261
TI  - Influenza vaccination and the 'diversity paradox'.
AB  - The antigenic evolution of influenza is widely assumed to occur by antigenic
      drift, in which strains incrementally acquire mutations in highly variable
      epitopes under strong immune selective pressure, such as those in the major
      influenza antigen haemagglutinin. However, this is not easy to reconcile with
      epidemiological observations, which show that each influenza season is dominated
      by a limited number of strains. Here, we discuss this paradox in light of recent
      influenza epidemics that have been characterised by low vaccine effectiveness and
      dominated by strains of limited antigenic and genetic diversity.

PMID- 30239262
TI  - Inhibitor Binding Studies of Mycobacterium tuberculosis MraY (Rv2156c): Insights
      from Molecular Modeling, Docking and Simulation Studies.
AB  - Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis
      (M.tb) or tubercule bacillus, and H37Rv is the most studied clinical strain. The
      recent development of resistance to existing drugs is a global healthcare
      challenge to control and cure TB. Hence, there is a critical need to discover new
      drug targets in M.tb. The members of peptidoglycan biosynthesis pathway are
      attractive target proteins for antibacterial drug development. We have performed
      the in-silico analysis of M.tb MraY (Rv2156c) integral membrane protein,
      constructed the 3D structure model of M.tb MraY based on homology modeling
      method. The validated model was complexed with antibiotic muraymycin D2 (MD2) and
      was used to generate structure-based pharmacophore model (e-pharmacophore). High
      throughput virtual screening (HTVS) of Asinex database and molecular docking of
      hits was performed to identify the potential inhibitors based on their mode of
      interactions with the key residues involved in M.tb MraY-MD2 binding. The
      validation of these molecules was performed using molecular dynamics (MD)
      simulations for two best identified hit molecules complexed with M.tb MraY in the
      lipid bilayer, dipalmitoylphosphatidyl-choline (DPPC) membrane. The results
      indicated the stability of the complexes formed and retained non-bonding
      interactions similar to MD2. These findings may help in the design of new
      inhibitors to M.tb MraY involved in peptidoglycan biosynthesis.

PMID- 30239263
TI  - Morbidity and mortality from road traffic crashes in children in Metro West, City
      of Cape Town - 2014.
AB  - The road traffic crash injury burden significantly impacts the lives of South
      African children. This study aimed to assess the fatal and non-fatal pattern of
      road traffic crash injury of children under 13 years old from Metro West, City of
      Cape Town, from 1 January until 31 December 2014. The data were stratified by
      age, sex and mechanism of road traffic crash. The overall mortality rate was 8.7
      per 100 000 population and pedestrians contributed the most to this burden
      (72.5%). There were more male children involved in a road traffic crash (p =
      0.0001). The greatest proportion of fatal and non-fatal road traffic crash
      injuries was observed in children aged 5-9 years. Fractures contributed to the
      greatest rate of years lived with disability (3.0 years of life lived with
      disability per 100 000). Our study found that the burden of road traffic crashes
      primarily affects male pedestrians aged 5-9 years old.

PMID- 30239264
TI  - In this issue: Antibodies and T Cell subtypes in diseases and therapy.

PMID- 30239265
TI  - Laser-Assisted Microdiscectomy for Far Lateral Lumbar Disc Herniation at the L5
      S1 Level.
AB  - OBJECTIVE: Laser-assisted paraspinal microdiscectomy for far lateral lumbar disc
      herniation (LDH) enables direct access to the foraminal or far lateral zone with
      minimal tissue injury and preserves facet joints, thereby preventing
      postoperative segmental instability. We demonstrated the clinical outcomes of
      this technique and discussed the pros and cons of laser use in lumbar disc
      surgery. BACKGROUND: The microdiscectomy technique for L5-S1 far lateral zone may
      be difficult due to the limited surgical field with narrowed disc space,
      hypertrophied facet, and sacral ala. Thus, we used carbon dioxide (CO2) laser for
      sophisticated decompression. METHODS: Eighty-four patients who were treated with
      microdiscectomy for far lateral LDH at the L5-S1 level were evaluated. Among
      them, 40 patients were treated using CO2 laser-assisted microdiscectomy, and the
      remaining 44 patients using conventional microdiscectomy. Perioperative and
      postoperative data were compared between the two groups with 2 years of follow
      up. Clinical outcomes were assessed using the visual analog scale (VAS), Oswestry
      disability index (ODI), and modified Macnab criteria. RESULTS: VAS and ODI
      significantly improved in both groups. An excellent or good outcome was rated in
      80% and 77.3% of the laser and conventional group, respectively. There was no
      significant difference in global outcomes. However, hospital stay and time to
      return to work were significantly shorter in the laser group (p < 0.05).
      CONCLUSIONS: CO2 laser-assisted paraspinal microdiscectomy is effective for
      treating far lateral LDH. The pinpoint laser scalpel enables delicate and
      complete decompression in a limited surgical field with minimal tissue trauma.

PMID- 30239266
TI  - Anti-Inflammatory Effect of Ginsenoside Rh2-Mix on Lipopolysaccharide-Stimulated
      RAW 264.7 Murine Macrophage Cells.
AB  - Ginsenoside Rh2, a protopanaxadiol saponin from ginseng, has been reported to
      have strong anti-inflammatory activity. However, the concentration of ginsenoside
      Rh2 is very low (>0.001%) in the total ginseng extracted, which is not enough for
      production despite its high pharmacological effects. Thus, in this study, we
      evaluated the anti-inflammatory effect of ginsenoside Rh2-mix (GRh2-mix) on
      lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. From the
      high-performance liquid chromatography analysis, it was confirmed that the GRh2
      mix was mainly composed of 20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3. The LPS-stimulated
      RAW 264.7 cells were treated with different concentrations of GRh2-mix (100, 200,
      400, 500 MUg/mL). The cell counting kit-8 assay showed that the GRh2-mix
      treatment increased cell proliferation in LPS-stimulated RAW 264.7 murine
      macrophage cells. The GRh2-mix inhibited nitric oxide production in a dose
      dependent manner, suggesting an anti-inflammatory effect. Furthermore, reverse
      transcription polymerase chain reaction and Western blot results also indicated
      that the GRh2-mix suppressed inflammatory genes such as iNOS, TNF-alpha, COX-2,
      IL-1beta, IL-6, and NF-kappaB. In summary, these results suggest that the GRh2
      mix exhibits anti-inflammatory activity via the downregulation of the NF-kappaB
      pathway and has high efficiency with a simple production procedure.

PMID- 30239267
TI  - School Attachment and Violent Attitudes Preventing Future Violent Behavior Among
      Youth.
AB  - Evidence derived from social information theories support the existence of
      different underlying cognitive mechanisms guiding violent behavior through life.
      However, a few studies have examined the contribution of school variables to
      those cognitive mechanisms, which may help explain violent behavior later in
      life. The present study examines the relationship between school attachment,
      violent attitudes, and violent behavior over time in a sample of urban
      adolescents from the U.S. Midwest. We evaluated the influence of school
      attachment on violent attitudes and subsequent violent behavior. We used
      structural equation modeling to test our hypothesis in a sample of 579
      participants (54.9% female, 81.3% African American). After controlling for gender
      and race, our results indicated that the relationship between school attachment
      and violent behavior over time is mediated by violent attitudes. The
      instrumentalization of the school context as a learning environment aiming to
      prevent future violent behavior is also discussed.

PMID- 30239269
TI  - Bathtub drowning mortality among older adults in Japan.
AB  - We examined the bathtub drowning mortality among older adults in Japan. Mortality
      data from Japan and 30 other Organization for Economic Co-operation and
      Development (OECD) countries were extracted from World Health Organization Cause
      of Death Query Online. During 2012-2014, unintentional drowning mortality rates
      in Japan were 9.5, 28.2 and 39.7 per 100,000 population for adults aged 65-74, 75
      84 and >=85 years, respectively-rates highest among the 31 OECD countries. In
      total, 6377 older adults aged >=65 years died from unintentional drowning in
      2014, of which 4857 (76%) deaths involved bathtubs. During 1995-2014, the bathtub
      drowning mortality rate for adults aged >=65 years was stable in Japan. During
      2011-2014, approximately 4800 older adults died from bathtub drowning annually.
      Death predominantly occurred 'while in a bathtub', rather than 'following a fall
      into a bathtub'. In 2014, 95% and 87% of bathtub drowning deaths among older
      women and men aged >=65 years, respectively, occurred at home. In conclusion,
      bathtub drowning deaths at home is an important public health problem among older
      adults Japanese and efforts are needed to reduce these preventable deaths.

PMID- 30239268
TI  - Ego Depletion Reduces Attention Control: Evidence From Two High-Powered
      Preregistered Experiments.
AB  - Two preregistered experiments with more than 1,000 participants in total found
      evidence of an ego depletion effect on attention control. Participants who
      exercised self-control on a writing task went on to make more errors on Stroop
      tasks (Experiment 1) and the Attention Network Test (Experiment 2) compared with
      participants who did not exercise self-control on the initial writing task. The
      depletion effect on response times was nonsignificant. A mini meta-analysis of
      the two experiments found a small ( d = 0.20) but significant increase in error
      rates in the controlled writing condition, thereby providing evidence of poorer
      attention control under ego depletion. These results, which emerged from
      preregistered experiments in large samples of participants, represent some of the
      most rigorous evidence yet of the ego depletion effect.

PMID- 30239270
TI  - The implications of intradural extension in paraspinal malignant peripheral nerve
      sheath tumors: effects on central nervous system metastases and overall survival.
AB  - OBJECTIVE: In this study, the authors sought to compare tumors with intradural
      extension to those remaining in the epidural or paraspinal space with the
      hypothesis that intradural extension may be a mechanism for seeding of the CSF
      with malignant cells, thereby resulting in higher rates of CNS metastases and
      shorter overall survival. METHODS: The authors searched the medical record for
      cases of malignant peripheral nerve sheath tumors (MPNSTs) identified from 1994
      to 2017. The charts of the identified patients were then reviewed for tumor
      location to identify patients with paraspinal malignancy. All patients included
      in the study had tumor specimens that were reviewed in the surgical pathology
      department. Paraspinal tumors with intradural extension were identified in the
      lumbar, sacral, and spinal accessory nerves, and attempts were made to match this
      cohort to another cohort of patients who had paraspinal tumors of the cranial
      nerves and lumbar and sacral spinal regions without intradural extension. Further
      information was collected on all patients with and without intradural extension,
      including date of diagnosis by pathology specimen review; nerve or nerves of
      tumor origin; presence, location, and diagnostic date of any CNS metastases; and
      either the date of death or date of last follow-up. RESULTS: The authors
      identified 6 of 179 (3.4%) patients who had intradural tumor extension and
      compared these patients with 12 patients who harbored paraspinal tumors that did
      not have intradural extension. All tumors were diagnosed as high-grade MPNSTs
      according to the surgical pathology findings. Four of 6 (66.7%) patients with
      intradural extension had documented CNS metastases. The presence of CNS
      metastases was significantly higher in the intradural group than in the
      paraspinal group (intradural, 66.7% vs paraspinal, 0%; p < 0.01). Time from
      diagnosis until death was 11.2 months in the intradural group and approximately
      72 months in the paraspinal, extradural cohort. CONCLUSIONS: In patients with
      intradural extension of paraspinal MPNSTs, significantly higher rates of CNS
      metastases are seen with a reduced interval of time from diagnosis to metastatic
      lesion detection. Intradural tumor extension is also a poor prognostic factor for
      survival, with these patients showing a reduced mean time from diagnosis to
      death.

PMID- 30239271
TI  - Cervical osteogenic degeneration in Japanese professional wrestlers and its
      relationship to cervical spine injury.
AB  - OBJECTIVE: This study aimed to investigate the characteristics of cervical
      degeneration in Japanese professional wrestlers and its relationship with the
      risk of cervical spine injury (CSI). METHODS: Since 2012, 27 Japanese male
      wrestlers belonging to a professional wrestling association have undergone
      periodical medical examinations of the cervical spine. If neurological symptoms
      were observed in the wrestlers, the resident trainers urged them to undergo a
      brief examination at the authors' institutions. In addition to this prospective
      research study, the mechanisms of the CSIs that occurred in 5 wrestlers,
      including 2 with CSI before 2012 and 3 who were independent from the professional
      wrestling association, were retrospectively investigated by reviewing the
      circumstances of the injury and the wrestlers' imaging studies. RESULTS: The mean
      age of the wrestlers was 36.9 years (range 23-56 years) at the initial
      examination. An anterior giant ossifying lesion (AGOL) was observed in the
      anterior aspect of the cervical spine of 11 wrestlers (41%). The AGOLs tended to
      grow and spread to multiple spinal levels as the wrestlers aged. Of the 12
      wrestlers with osteogenic lesions, 10 older than 40 years of age (83%) had an
      AGOL, which is frequently accompanied by osseous spinal canal stenosis. Two
      wrestlers presented with spinal cord compression with intramedullary intensity
      change on MRI. However, during the follow-up period, no spinal cord injury (SCI)
      occurred in the wrestlers, although thoracolumbar injury occurred in 2 wrestlers
      during a match. In examining the 5 wrestlers with CSI, the injury occurred at the
      spinal levels without an AGOL. The most frequent pathology of CSI (60%) was SCI
      at the spinal level adjacent to the multilevel AGOL. CONCLUSIONS: AGOL is a
      peculiar cervical degeneration of Japanese professional wrestlers, especially in
      aged wrestlers. The AGOL appears to be a biological reaction to reinforce the
      anterior aspect of the cervical spine of professional wrestlers, who routinely
      defend themselves in a flexed neck posture against their opponent. The present
      results suggest that the risk of CSI is not increased by spinal canal stenosis
      accompanied by AGOL. Further studies are needed to investigate the relationship
      between the wrestlers' cervical degeneration and the risk of CSI in more detail.

PMID- 30239272
TI  - Etiological Pathways to Rejection Sensitivity in a High-Risk Sample.
AB  - Rejection sensitivity is associated with social-emotional maladjustment in both
      childhood and adulthood. However, less is known about the etiology of rejection
      sensitivity. The present study tests an etiological model for rejection
      sensitivity using a high-risk sample ( N = 227) with prospective data from
      infancy (i.e., 12 months) to adolescence (i.e., eighth grade). Evidence for
      social learning and attachment theories was demonstrated. In particular, family
      and parenting factors, such as family conflict and maternal harshness, were
      predictive of rejection sensitivity in adolescence. Implications for intervention
      and prevention efforts are discussed.

PMID- 30239273
TI  - Preparing non-medical clinicians to deliver GP out-of-hours services: lessons
      learned from an innovative approach.
AB  - Despite the need to develop a non-medical out-of-hours (OOHs) workforce to
      address increasing healthcare demands and to support a strained GP workforce,
      there is no consensus on the required training and clinical competencies needed
      for nurses and paramedics to be developed as safe OOH practitioners. This paper
      presents the development and evaluation of one programme delivered in 2017 to
      paramedics seeking to work in OOHs services. Details of the course delivery are
      outlined and the mixed-methods evaluation presented. Following successful
      university ethical approval, student and staff experiences were reviewed through
      interviews, questionnaires and graded feedback of completed electronic patient
      case records. The findings provided useful learning that can be transferred to
      other organisations seeking to develop such training. In particular, the findings
      suggest the course was able to provide the students with the skills, knowledge
      and confidence to become safe practitioners in the OOHs service. Challenges in
      course delivery were highlighted. It was suggested that course organisation,
      duration and scope require careful consideration to enable students to complete
      and practise successfully.

PMID- 30239274
TI  - Contextual support for children's recall within working memory.
AB  - Measures of working memory capacity (WMC) are extremely popular, yet we know
      relatively little about the specific processes that support recall. We focused on
      children's and adults' ability to use contextual support to access working memory
      representations that might otherwise not be reported. Children ( N = 186, 5-10
      years) and adults ( N = 64) completed a listening span task and a delayed recall
      task with semantic probes or cues. Clear age-related increases in listening span
      were evident. All age groups benefitted from contextual support to retrieve
      degraded target memoranda, particularly on listening span tasks when the cues
      provided semantic support for processing events, in comparison to cues associated
      specifically with memoranda. Response latencies suggested a developing efficiency
      in children's use of contextual support for delayed recall correlated with
      listening span performance. These probe tasks support accounts of working memory
      that recognise reconstructive and cued search processes.

PMID- 30239275
TI  - Moderating Factors Associated With Interrupting the Transmission of Domestic
      Violence Among Adolescents.
AB  - Exposure to child maltreatment in the family-of-origin has consistently been
      linked to intimate partner violence (IPV) perpetration in adulthood. Although the
      concept of a cycle of violence presumes that the transmission of violence is
      expressed directly across generations, some protective factors such as social
      support, self-esteem, and relationship quality with parents may ultimately be
      influential in nonviolent behavior in adult relationships. Using the National
      Longitudinal Study of Adolescent Health data set, we tested protective factors to
      see if and to what extent they disrupted the association from early childhood
      maltreatment to experiencing violence later on in adult relationships. We found
      that there was a positive association between adolescence exposure to
      maltreatment and adult perpetration and victimization of IPV. Also, social
      support in adolescence was identified as a predictor of lower levels of violence
      in adult relationship. Clinical implications were discussed to help therapists
      intervene with adolescents in the hopes of reducing their propensity toward
      violent relationships in adulthood.

PMID- 30239276
TI  - Development and evaluation of a multiplex reverse-transcription real-time PCR
      assay for detection of equine respiratory disease viruses.
AB  - We developed a multiplex reverse-transcription real-time PCR (RT-rtPCR) assay for
      the simultaneous detection of the main equine respiratory viruses: equid
      alphaherpesviruses 1 and 4 (EHV-1, -4) and equine influenza virus (EIV; species
      Influenza A virus). The primers and probes amplified only the targeted viruses,
      and there were no inter-assay cross-amplifications or nonspecific interactions.
      The multiplex assay efficiencies were 92.5%, 97%, and 90% for EHV-1, EHV-4, and
      EIV, respectively. The R2 values of the monoplex and multiplex assays were
      ?0.990, and the slopes were -3.37 to -3.59. The performance of the assay was
      evaluated by analyzing 152 samples from clinically infected horses. EHV-1 DNA was
      detected in 12 samples, EHV-4 DNA in 9 samples, and both EHV-1 and EHV-4 in 4
      samples. The accuracy of the assay was confirmed by comparing these results using
      commercial rtPCR and RT-rtPCR kits. Our multiplex RT-rtPCR was a sensitive,
      specific, accurate, and cost-effective method for the detection of the target
      viruses whether they occur alone or as part of coinfections.

PMID- 30239277
TI  - The Management of Opioid-Induced Nausea and Vomiting in Patients with Cancer: A
      Systematic Review.
AB  - BACKGROUND: Opioids are the foundation of treatment for cancer pain but can cause
      side-effects, one of the most common being nausea and vomiting, which can impair
      quality of life. OBJECTIVE: To evaluate the evidence for the management of opioid
      induced nausea and vomiting. This systematic review was undertaken as part of an
      update of the European Association for Palliative Care's opioid guidelines.
      DESIGN: Searches of MEDLINE (1966-2017) and EMBASE (1980-2017) were done. Key
      eligibility criteria were: randomized controlled trials conducted in patients
      with cancer. The Grading of Recommendations Assessment Development and
      Evaluations system was applied to formulate recommendations. RESULTS: Fifteen
      studies were eligible (1524 patients). The studies were grouped as follows:
      opioid switching (n = 8); the use of antiemetics to treat opioid-induced nausea
      and vomiting (n = 4); and change of route of administration of the opioid (n =
      3). Three recommendations were formulated: A weak recommendation for switching
      from morphine to oxycodone in cancer patients with nausea (quality D); a weak
      recommendation for switching from tramadol to either codeine or hydrocodone for
      pain in cancer patients with nausea (quality D); and a weak recommendation for
      switching from morphine/oxycodone to methadone using the three-day switch method
      in patients with increasing pain considered untreatable with further opioid
      titration and/or with opioid-related side effects (quality C). CONCLUSIONS: This
      systematic review can make only weak recommendations for the management of opioid
      induced nausea and vomiting. There remains a need for high-quality studies before
      strong recommendations on the management of opioid-induced nausea and vomiting
      can be made.

PMID- 30239278
TI  - Effects of Mild Hypothermia on Cardiac and Neurological Function in Piglets Under
      Pathological and Physiological Stress Conditions.
AB  - To investigate the different effects of mild hypothermia on pathological and
      physiological stress conditions in piglets, 30 pigs were randomized into four
      groups: cardiac arrest and mild hypothermia (CA-MH group), cardiac arrest and
      normothermia (CA-NH group), non-CA-MH (NCA-MH group), and a sham operation. The
      same hypothermia intervention was implemented in both CA-MH and NCA-MH groups.
      The CA-NH group did not undergo therapeutic hypothermia after resuscitation. The
      hemodynamic parameters were recorded. Cerebral metabolism variables and
      neurotransmitters in the extracellular fluid were collected through microdialysis
      tubes. The serum of venous blood was used to detect levels of inflammatory
      factors. The cerebral function was evaluated. At 24 and 72 hours after
      resuscitation, the cerebral performance category and neurological deficit score
      in the CA-NH group had higher values. Heart rate and cardiac output (CO) in the
      CA-MH group during cooling were lower than that of the CA-NH group, but CO was
      higher after rewarming. Glucose was higher during cooling, and extracellular
      lactate and lactate/pyruvate ratio in the CA-MH group were lower than that of the
      CA-NH group. Noradrenaline and 5-hydroxytryptamine in the CA-MH and NCA-MH groups
      were lower than that of the CA-NH group and sham group during cooling,
      respectively. Inflammatory factor levels, including interleukin (IL)-1beta, IL-2,
      IL-4, IL-6, IL-8, and tumor necrosis factor-alpha, in the CA-MH group were lower
      than that of the CA-NH group at cooling for 12 hours. These values in the NCA-MH
      group were higher than that of the sham group. Under a light and an electron
      microscope, the worse pathological results of heart and brain were observed in
      the two cardiac arrest groups. Mild hypothermia can provide limited organ
      protection in the specific pathological condition caused by ischemia-reperfusion,
      but it may produce a negative effect in a normal physiological state.

PMID- 30239279
TI  - Oxidative stress response to air particle pollution in a rat nutritional growth
      retardation model.
AB  - Air pollution consisting of gases and particulate matter-(PM) represents a health
      problem in cities worldwide. However, air pollution does not impact equally all
      individuals, as children appear to be more vulnerable subpopulations. Air
      pollution and malnutrition are two distinct factors that have been associated
      with oxidative damage. Therefore, the interaction between environmental exposure
      and nutritional status in populations at risk needs to be explored. The aim of
      this study was to examine oxidative metabolism in lung, heart and liver in
      malnourished young rats exposed to residual oil fly ash (ROFA). A Nutritional
      Growth Retardation (NGR) model was developed in weanling male rats placed on a
      20% restricted balanced diet for 4 weeks. Then, NGR and control rats were
      intranasally instilled with either ROFA (1mg/kg BW) or phosphate buffered saline
      (PBS). Twenty-four hr post-exposure lung, heart and liver were excised, and serum
      collected. ROFA induced lung and liver inflammation in control and NGR animals as
      evidenced by lung polymorphonuclear neutrophil (PMN) recruitment and alveolar
      space reduction accompanied by liver lymphocyte and binucleated hepatocyte level
      increase. In lung and liver, antioxidant defense mechanisms reduced
      lipoperoxidation. In contrast, only in NGR animals did ROFA exposure alter heart
      oxidative metabolism leading to lipid peroxidation. Although histological and
      biochemical tissue alterations were detected, no marked changes in serum liver
      and heart systemic biomarkers were observed. In conclusion, NGR animals responded
      differently to PM exposure than controls suggesting that nutritional status plays
      a key role in responsiveness to ambient air contaminants.

PMID- 30239280
TI  - Effects of Age on Dual-Task Walking While Listening.
AB  - This study examined the effects of age on single- and dual-task listening and
      walking during virtual street crossing. Seventeen younger and 12 older adults
      participated. In each listening trial, three sentences were presented
      simultaneously from separate locations. Participants were instructed to report
      the target sentence. Predictability of the target sentence location was varied.
      Treadmill walking was measured using motion analysis. Measures included word
      recognition accuracy, head and trunk angles, and spatiotemporal gait parameters.
      Older adults exhibited a more upright head alignment and less variability in
      stride time during dual-tasking, particularly under less certain target sentence
      location conditions. Younger adults' walking was unaffected by dual-task demands.
      Together, the results indicate greater postural prioritization in older adults
      than young.

PMID- 30239281
TI  - Intracranial hypertension following sacrifice of occipital and marginal sinuses
      during posterior fossa decompression for Chiari I malformation: case report.
AB  - The occipital and marginal sinuses, when present, must be sacrificed in order to
      open the dura in most posterior fossa surgeries in the pediatric population,
      including posterior fossa decompression for Type I Chiari malformation (CM-I)
      with duraplasty. Apart from the immediate risk of hemorrhage, the voluntary
      occlusion of this structure is almost universally well tolerated. The authors
      report a case of intracranial hypertension following the sacrifice of occipital
      and marginal sinuses following posterior fossa decompression with duraplasty for
      CM-I. The specific draining pattern variant of the occipital and marginal sinuses
      leading to this complication as well as avoidance and management strategies of
      this condition are discussed.

PMID- 30239282
TI  - Nationwide incidence and risk factors for posttraumatic seizures in children with
      traumatic brain injury.
AB  - OBJECTIVE: Posttraumatic seizures (PTSs) are the most common complication
      following a traumatic brain injury (TBI) and may lead to posttraumatic epilepsy.
      PTS is well described in the adult literature but has not been studied
      extensively in children. Here, the authors utilized the largest nationwide
      registry of pediatric hospitalizations to report the national incidence, risk
      factors, and outcomes associated with PTS in pediatric TBI. METHODS: The authors
      queried the Kids' Inpatient Database (KID) using ICD-9-CM codes to identify all
      patients (age < 21 years) who had a primary diagnosis of TBI (850.xx-854.xx) and
      a secondary diagnosis of PTS (780.33, 780.39). Parameters of interest included
      patient demographics, preexisting comorbidities, hospital characteristics, nature
      of injury (open/closed), injury type (concussion, laceration/contusion,
      subarachnoid hemorrhage, subdural hematoma, or epidural hematoma), loss of
      consciousness (LOC), surgical management (Clinical Classification Software code 1
      or 2), discharge disposition, in-hospital complications, and in-hospital
      mortality. The authors utilized the IBM SPSS statistical package (version 24) for
      univariate comparisons, as well as the identification of independent risk factors
      for PTS in multivariable analysis (alpha set at < 0.05). RESULTS: The rate of PTS
      was 6.9% among 124,444 unique patients hospitalized for TBI. The utilization rate
      of continuous electroencephalography (cEEG) was 0.3% and increased between 2003
      (0.1%) and 2012 (0.7%). The most common etiologies of TBI were motor vehicle
      accident (n = 50,615), accidental fall (n = 30,847), and blunt trauma (n =
      13,831). However, the groups with the highest rate of PTS were shaken infant
      syndrome (41.4%), accidental falls (8.1%), and cycling accidents (7.4%). In
      multivariable analysis, risk factors for PTS included age 0-5 years (compared
      with 6-10, 11-15, and 16-20 years), African American race (OR 1.4), >= 3
      preexisting comorbidities (OR 4.0), shaken infant syndrome (OR 4.4), subdural
      hematoma (OR 1.6), closed-type injury (OR 2.3), brief LOC (OR 1.4), moderate LOC
      (OR 1.5), and prolonged LOC with baseline return (OR 1.8). Surgically managed
      patients were more likely to experience PTS (OR 1.5) unless they were treated
      within 24 hours of admission (OR 0.8). PTS was associated with an increased
      likelihood of in-hospital complications (OR 1.7) and adverse (nonroutine)
      discharge disposition (OR 1.2), but not in-hospital mortality (OR 0.5). The
      overall utilization rate of cEEG was 1.3% in PTS patients compared with 0.2% in
      patients without PTS. Continuous EEG monitoring was associated with higher rates
      of diagnosed PTS (35.4% vs 6.8%; OR 4.9, p < 0.001). CONCLUSIONS: PTS is common
      in children with TBI and is associated with adverse outcomes. Independent risk
      factors for PTS include younger age (< 5 years), African American race, increased
      preexisting comorbidity, prolonged LOC, and injury pattern involving cortical
      exposure to blood products. However, patients who undergo urgent surgical
      evacuation are less likely to develop PTS.

PMID- 30239283
TI  - Examining the need for routine intensive care admission after surgical repair of
      nonsyndromic craniosynostosis: a preliminary analysis.
AB  - OBJECTIVE: At British Columbia Children's Hospital (BCCH), pediatric patients
      with nonsyndromic craniosynostosis are admitted directly to a standard surgical
      ward after craniosynostosis surgery. This study's purpose was to investigate the
      safety of direct ward admission and to examine the rate at which patients were
      transferred to the intensive care unit (ICU), the cause for the transfer, and any
      patient characteristics that indicate higher risk for ICU care. METHODS: The
      authors retrospectively reviewed medical records of pediatric patients who
      underwent single-suture or nonsyndromic craniosynostosis repair from 2011 to 2016
      at BCCH. Destination of admission from the operating room (i.e., ward or ICU) and
      transfer to the ICU from the ward were evaluated. Patient characteristics and
      operative factors were recorded and analyzed. RESULTS: One hundred fourteen
      patients underwent surgery for single-suture or nonsyndromic craniosynostosis.
      Eighty surgeries were open procedures (cranial vault reconstruction,
      frontoorbital advancement, extended-strip craniectomy) and 34 were minimally
      invasive endoscope-assisted craniectomy (EAC). Sutures affected were sagittal in
      66 cases (32 open, 34 EAC), coronal in 20 (15 unilateral, 5 bilateral), metopic
      in 23, and multisuture in 5. Only 5 patients who underwent open procedures (6%)
      were initially admitted to the ICU from the operating room; the reasons for
      direct admission were as follows: the suggestion of preoperative elevated
      intracranial pressure, pain control, older-age patients with large reconstruction
      sites, or a significant medical comorbidity. Overall, of the 107 patients
      admitted directly to the ward (75 who underwent an open surgery, 32 who underwent
      an EAC), none required ICU transfer. CONCLUSIONS: Overall, the findings of this
      study suggest that patients with nonsyndromic craniosynostosis can be managed
      safely on the ward and do not require postoperative ICU admission. This could
      potentially increase cost savings and ICU resource utilization.

PMID- 30239284
TI  - The role of lumboperitoneal shunts in managing chronic hydrocephalus with slit
      ventricles.
AB  - OBJECTIVE: Lumboperitoneal (LP) shunts have a role not only in pseudotumor
      cerebri, but also in patients with slit-like ventricles who are treated with CSF
      shunting on a chronic basis. Hesitation to utilize LP shunts is based on previous
      conventional beliefs including the tendency for overdrainage, difficulties
      accessing the shunt to tap or revise, and risk of progressive cerebellar
      tonsillar herniation. The authors hypothesized that the use of horizontal
      vertical (HV) valves may reduce the risk of these complications, particularly
      overdrainage and development of Chiari malformation. METHODS: All pediatric cases
      involving patients treated with an LP shunt at the Children's Hospital of
      Michigan were reviewed in this retrospective case series. A total of 143 patients
      with hydrocephalus were treated with LP shunts from 1997-2015 (follow-up range 8
      months-8 years, median 4.2 years). Patients with pseudotumor cerebri underwent
      placement of an LP shunt as a primary procedure. In patients with slit ventricles
      from chronically treated hydrocephalus or repeated shunt malfunctions from
      proximal catheter obstruction, a lumbar drain was inserted to assess candidacy
      for conversion to an LP shunt. In patients who tolerated the lumbar drain and
      demonstrated communication of the ventricles with the spinal cisterns, treatment
      was converted to an LP shunt. All patients included in the series had undergone
      initial shunt placement between birth and age 16 years. RESULTS: In 30% of
      patients (n = 43), LP shunts were placed as the initial shunt treatment; in 70%
      (n = 100), treatment was converted to LP shunts from ventriculoperitoneal (VP)
      shunts. The patients' age at insertion of or conversion to an LP shunt ranged
      from 1 to 43 years (median 8.5 years). Of the patients with clear pre-LP and post
      LP shunt follow-up imaging, none were found to develop an acquired Chiari
      malformation. In patients with pre-existing tonsillar ectopia, no progression was
      noted on follow-up MRIs of the brain in these patients after LP shunt insertion.
      In our LP shunt case series, no patient presented with acute deterioration from
      shunt malfunction. CONCLUSIONS: Conversion to an LP shunt may minimize acute
      deterioration from shunt malfunction and decrease morbidity of repeated
      procedures in patients with chronically shunt-treated hydrocephalus and small
      ventricles. In comparison to previously published case series of LP shunt
      treatment, the use of LP shunts in conjunction with HV valves may decrease the
      overall risk of cerebellar tonsillar herniation. The use of an LP shunt may be an
      alternative in the management of slit ventricles when VP shunting repeatedly
      fails.

PMID- 30239285
TI  - News from the European College of Laboratory Animal Medicine.

PMID- 30239286
TI  - Update from the Editors.

PMID- 30239287
TI  - Submit your abstract for the 14th FELASA Congress.

PMID- 30239288
TI  - Impact of vitamin D depletion during development on mouse sperm DNA methylation.
AB  - Suboptimal environmental conditions during development can substantially alter
      the epigenome. Stable environmentally-induced changes to the germline epigenome,
      in particular, have important implications for the health of the next generation.
      We showed previously that developmental vitamin D depletion (DVD) resulted in
      loss of DNA methylation at several imprinted loci over two generations. Here, we
      assessed the impact of DVD on genome-wide methylation in mouse sperm in order to
      characterize the number, extent and distribution of methylation changes in
      response to DVD and to find genes that may be susceptible to this prevalent
      environmental perturbation. We detected 15,827 loci that were differentially
      methylated in DVD mouse sperm vs. controls. Most epimutations (69%) were loss of
      methylation, and the extent of methylation change and number of CpGs affected in
      a region were associated with genic location and baseline methylation state.
      Methylation response to DVD at validated loci was only detected in offspring that
      exhibited a phenotypic response to DVD (increased body and testes weight)
      suggesting the two types of responses are linked, though a causal relationship is
      unclear. Epimutations localized to regions enriched for developmental and
      metabolic genes and pathway analyses showed enrichment for Cadherin, Wnt, PDGF
      and Integrin signaling pathways. These findings show for the first time that
      vitamin D status during development leads to substantial DNA methylation changes
      across the sperm genome and that locus susceptibility is linked to genomic and
      epigenomic context.

PMID- 30239289
TI  - Undergraduate students survey their peers on mental health: Perspectives and
      strategies for improving college counseling center outreach.
AB  - OBJECTIVE: The purpose of the study was to examine student perspectives about
      college mental health including the primary mental health issues affecting
      students, common college student stressors, student awareness of campus mental
      health resources, and mental health topics students want more information about.
      PARTICIPANTS: Participants were 822 undergraduate and graduate students enrolled
      in a private university. The study was conducted during September 2016. METHODS:
      As part of a public health course in program planning, undergraduate students
      surveyed their peers about their experience with mental health and mental health
      resources. RESULTS: Stress was perceived as the largest mental health issue.
      Students most wanted more information about school/work/life balance followed by
      stress management. Electronic newsletters, social media, and on-campus seminars
      were the top strategies that students suggested as ways to reach them.
      CONCLUSIONS: The results provide student perspectives on mental health that may
      be useful in developing effective outreach efforts.

PMID- 30239290
TI  - Is Postexercise Blood Flow Restriction a Viable Alternative to Other Resistance
      Exercise Protocols?
AB  - PURPOSE: The purpose of this study was to identify whether post-resistance
      exercise (REx) blood flow restriction (BFR) can elicit a similar acute training
      stimulus to that offered by either heavy REx or traditional low-load BFR REx.
      METHOD: Ten men completed trials with 30% one-repetition maximum (1RM) for 5 sets
      of 15 repetitions without BFR (30%), with BFR during exercise (30% RD), and with
      postexercise BFR (30% RP) and at 75% 1RM for 3 sets of 10 repetitions. Lactate
      and cortisol were measured before and up to 60 min after exercise. Thigh
      circumference, ratings of perceived exertion (RPE), and pain were measured before
      and after exercise. Surface electromyography was measured during exercise.
      RESULTS: All conditions had a large effect (effect size [ES] > 0.8) on lactate,
      with the largest effects observed with the 75% condition; no differences were
      observed between the 30% conditions. All conditions had a moderate effect (ES >
      0.25 <= 0.4) on increasing thigh circumference. This effect was maintained (ES =
      0.35) with the application of BFR after REx (30% RP). Change in RPE, from the
      first to last set, was significantly greater with 30% RD compared with other
      conditions (all p < .05). Electromyography amplitude was higher and percentage
      change was greater for the 75% condition compared with the other conditions (both
      p < .05). CONCLUSIONS: The application of BFR immediately post-REx altered
      several of the responses associated with REx that is aimed at inducing muscular
      hypertrophy. Additionally, these changes occurred with less pain and perceived
      exertion suggesting that this form of REx may offer an alternative, tolerable
      method of REx.

PMID- 30239291
TI  - On the Feasibility of Ultrasound Imaging Enrichment by Medium-Temperature
      Changes.
AB  - We describe the concept of a new imaging modality based on the tracking and
      dynamic modeling of local intensity changes (ICs) observed in conventional
      ultrasound images collected during a medium-temperature change. We computed the
      pixel-by-pixel IC from averaged B-mode images that exhibited different behaviors
      with varying temperature resulting from changes in the speed of sound, which
      consequently induce changes in the backscattered energy. Moreover, for each
      pixel, a first-order polynomial model was adjusted to the different temperature
      dependent ICs. The representation of the polynomial angular parameter in 2D pixel
      space was used to obtain a parametric image. The results obtained by simulations
      and with real B-mode images indicated that this new ultrasound imaging modality
      was able to enhance the contrast and highlight structures that were poorly
      visible or even undetected in conventional images. A temperature change of 3
      degrees C was found to be sufficient to generate appropriate images with the
      proposed method. In addition, if a temperature change of 6 degrees C was
      considered, the thermal dose, measured as the cumulative number of equivalent
      minutes at 43 degrees C (CEM43 degrees C), was 2.4 CEM43 degrees C, which is a
      value that is considered safe according to the literature. We provide a proof-of
      concept of a new imaging modality that opens new opportunities for the
      enhancement of ultrasound images and consequently contributes to improvements in
      ultrasound-based diagnoses. Our approach is based on images returned by
      commercial ultrasound scanners. Therefore, it can be implemented in any
      ultrasound system and is independent of specific ultrasound hardware and software
      data acquisition characteristics.

PMID- 30239292
TI  - Effects of Rudgea viburnoides (Cham.) Benth. (Rubiaceae) Leaves on Metabolic and
      Inflammatory Dysfunction Induced by High Refined Carbohydrate-Containing Diet in
      Mice.
AB  - Obesity is characterized by a chronic low-grade inflammation, which has been
      shown to be involved in the development of comorbidities such as insulin
      resistance, glucose intolerance, and liver damage. Phytochemicals found in plants
      may modulate inflammation and improve health problems associated with the excess
      of adiposity. Teas prepared with many plants are used in Brazil for losing
      weight. In this study, we evaluated the potential of Rudgea viburnoides (Cham.)
      Benth. on metabolic and inflammatory disarrangement induced by high refined
      carbohydrate (HC)-containing diet in mice. BALB/c mice were fed with chow or HC
      diet for 8 weeks. After this period, the HC diet was supplemented for 4 weeks
      with three different doses, 40, 80, and 160 mg/kg, of crude extract of R.
      viburnoides. Ethanol extract at the lowest dose (40 mg/kg) reduced adipocyte
      size, and improved glucose tolerance and insulin sensitivity. A lower
      concentration of proinflammatory mediators such as tumor necrosis factor-alpha,
      interleukin-6, and CCL2 in the liver and adipose tissue, and reduced levels of
      cholesterol and resistin in the serum were also observed. High concentrations of
      chlorogenic and caffeic acids, and the flavonoids, rutin and quercetin, were
      confirmed by high-performance liquid chromatography/diode array detector.
      Therefore, these data confirm the potential of R. viburnoides leaves as
      nutraceutical agents for the treatment of metabolic and inflammatory changes
      associated with obesity.

PMID- 30239294
TI  - Preparing for Practice: Strengthening Third-Year Medical Students' Awareness of
      Point-of-Care Resources.
AB  - This column describes the development and implementation of a responsive library
      course designed to train third-year medical students as they begin their
      clerkships. The course design consisted of a brief face-to-face introduction
      during third-year orientation and an online course developed in Canvas, an online
      learning management system. The objective of the course was to not only introduce
      students to the resources but also to teach them how to effectively use those
      resources at the point-of-care. Students evaluated the course to assess the
      overall effectiveness of the instruction. Course development and content,
      feedback provided by students, as well as suggestions for improvement are
      discussed.

PMID- 30239293
TI  - Apparently high Leptospira antibody seropositivity in donkeys for slaughter in
      three municipalities in Durango, Mexico.
AB  - We determined the seropositive percentage and the determinants of Leptospira
      exposure in domestic donkeys presented for slaughter in the State of Durango,
      Mexico. We examined 194 donkeys in 4 gathering premises. Sera of donkeys were
      analyzed for anti- Leptospira IgG antibodies using a microscopic agglutination
      assay with a panel of 7 Leptospira antigens. The association between Leptospira
      seropositivity and general characteristics of donkeys was assessed by bivariate
      and multivariate analyses. Antibodies against Leptospira (for at least 1 of the 7
      Leptospira serovars examined) were found in 151 of 194 (77.8%) donkeys.
      Seropositive donkeys were found in all regions, municipalities, and premises
      examined. The predominant serovar was L. interrogans Icterohaemorrhagiae ( n =
      117; 60.3%), followed by L. interrogans Sejroe ( n = 96; 49.5%), L. interrogans
      Canicola ( n = 10; 5.2%), L. kirschneri Grippotyphosa ( n = 6; 3.1%), L.
      borgpetersenii Ballum ( n = 5; 2.6 %), L. biflexa Semaranga ( n = 3; 1.5%), and
      L. noguchii Panama ( n = 2; 1%). Leptospira seropositivity was associated with
      gathering premises (OR = 2.64; 95% CI: 1.27-5.46; p = 0.009) and municipalities
      (OR = 0.11; 95% CI: 0.01-0.78; p = 0.02). Our results demonstrate an apparently
      high seropositive percentage of Leptospira infection in the donkeys studied in
      Mexico.

PMID- 30239295
TI  - Encouraging Engagement with Students and Integrating Librarians into the
      Curriculum through a Personal Librarian Program.
AB  - Five years ago, the Harriet F. Ginsburg Health Sciences Library created a
      Personal Librarian Program (PLP) to encourage librarian engagement with first-
      and second-year medical students and to promote awareness of library resources
      and services. Prior to the creation of the PLP, the library struggled with
      finding ways to connect with its medical students, especially because the library
      is 98% digital. The PLP was created to give students an individualized library
      experience and an easier way to interact with librarians. As a result,
      opportunities for librarian-student engagement increased, and Personal Librarian
      groups facilitated the integration of librarians into two first- and second-year
      medical school courses.

PMID- 30239297
TI  - Genetics Home Reference: A Review.
AB  - Genetics Home Reference is a free, online resource created and maintained by the
      National Library of Medicine. It is designed to provide genetic information to a
      wide variety of audiences, particularly the general public. The site consists of
      original information and links to other curated resources.

PMID- 30239298
TI  - Reference Managers that Support Collaborative Research: Dreaming of the Perfect
      Fit.
AB  - Reference or citation managers aid in capturing and managing citations and
      associated full text, tracking references and citing them properly in
      manuscripts, and creating bibliographies. With more features than ever, selecting
      the most appropriate reference manager can be overwhelming for users and
      librarians. One common situation in which librarians are asked for advice
      involves building shared libraries of references to support collaborative group
      work. This project developed a structured evaluation for comparison of several
      common citation managers and prototypical use cases to help match features with
      user needs, preferences, and workflows. As products evolve and needs change, is
      there a "perfect fit"?

PMID- 30239299
TI  - Community Engagement at an Emerging Academic Medical Library: A Three-Pronged
      Outreach Model.
AB  - The Oakland University William Beaumont School of Medicine's (OUWB) service
      oriented mission and vision is reflected in all aspects of the school including
      its culture, curriculum, research, community engagement, and the OUWB Medical
      Library. Though starting informally, the OUWB Medical Library's outreach program
      has matured and now sustains a wide array of activities each year. This outreach
      program has blossomed into a three-pronged model that is inclusive of activities
      and endeavors engaging the institution and local community: integrate, partner,
      and create. Among its successes and challenges, the library's ongoing outreach
      efforts have showcased the value of libraries in promoting community health and
      meaningfully contributing to the institutional mission.

PMID- 30239300
TI  - Deep Learning and Online Video: Advances in Transcription, Automated Indexing,
      and Manipulation.
AB  - In recent years, the amount of video content created and uploaded to the Internet
      has grown exponentially. Video content has unique accessibility challenges:
      indexing, transcribing, and searching video has always been very labor intensive,
      and there were no automated ways of searching videos for specific content. New
      software tools that use deep learning methods are automating some of these
      processes, making video content more discoverable and useful. There are also many
      new tools for processing and manipulating video in interesting ways. This column
      will briefly discuss the idea of deep learning and how deep learning tools can be
      used to transcribe, translate, search, and even manipulate videos. It will
      suggest ways that librarians can use these tools to help their institutions
      better manage video content. It also includes a list of video-related software
      tools.

PMID- 30239301
TI  - Clinical Medical Librarian Licensure: Pros versus Cons.
AB  - In hospitals and clinics, anyone who "touches" a patient has a license
      authorizing them to do so-from the phlebotomist to the cardiologist, from the
      genetic counselor to the social worker, and so on, except for the clinical
      medical librarian. This column discusses the intent versus the realities of
      occupational licensure for clinical medical librarians and provides
      recommendations for next steps.

PMID- 30239302
TI  - The (Un)Common Instructor: A New Role for Medical Librarians Beyond Information
      Literacy.
AB  - University common reading programs provide a shared experience as students
      transition into college life and develop critical thinking skills. Typically in
      such programs, all students in an incoming class read and discuss the same book.
      Conversely, the University of Florida Honors Program's (un)common reads
      facilitates the same skills development through multiple small sections, each
      focusing on a different book and each with flexible and innovative assignments
      and activities. Health Science Center librarians have taught in these (un)common
      reads since the spring semester 2010-2011. This article describes librarian
      involvement in this program as well as the ensuing benefits for students,
      librarians, and the university at large.

PMID- 30239306
TI  - Partnering to Analyze Selection of Resources by Medical Students for Case-Based
      Small Group Learning: A Collaboration between Librarians and Medical Educators.
AB  - Librarians and medical educators analyzed the quality of information resources
      used by first- and second-year medical students in their case-based small group
      learning summaries. Librarians provided instruction on using library resources
      and gave formal feedback to students about appropriate resources for basic
      science and clinical questions. The team found that students used a high number
      of clinical and basic science journal articles and textbooks with a number of
      factors influencing their resource choices. The study demonstrates numerous areas
      where librarians can play a key role in assisting students to find and assess
      information to answer clinical questions.

PMID- 30239307
TI  - Relationship Dissatisfaction, Emotion Regulation, and Physical Intimate Partner
      Aggression in Heavy-Drinking, Conflict-Prone Couples: A Dyadic Analysis.
AB  - Relationship dissatisfaction is a known risk factor for intimate partner
      aggression (IPA). However, the possible effect of weak emotion regulation skills
      on this association is unclear, particularly in couples at risk for violence who
      drink alcohol heavily. This study examined the moderating effect of emotion
      regulation on the association between relationship dissatisfaction and physical
      IPA perpetration within a dyadic framework. Participants were 583 heavy drinking
      couples ( N = 1,166) with a recent history of psychological and/or physical IPA
      recruited from two metropolitan cities in the United States. Multilevel models
      were used to examine effects within an actor-partner interdependence framework.
      Gender, Actor dissatisfaction, and Actor and Partner emotion regulation were
      associated with greater physical IPA perpetration. Actor relationship
      dissatisfaction predicted significantly greater physical IPA perpetration in
      Actors characterized by weak versus strong emotion regulation. Furthermore,
      partner relationship dissatisfaction predicted significantly increased physical
      IPA perpetration in Actors reporting weak, versus strong, emotion regulation.
      Gender did not significantly interact with model variables. Utilizing the I3
      metatheoretical model of IPA within a dyadic framework, results provide insight
      into the interactive effects of relationship dissatisfaction and emotion
      regulation deficits on physical IPA perpetration, particularly in those
      individuals already at risk for perpetration.

PMID- 30239310
TI  - Letter to the Editor. Hydrocephalus following decompressive hemicraniectomy: a
      foe or a silent bystander?

PMID- 30239309
TI  - Resveratrol restores the level of key inflammatory cytokines and RANKL/OPG ratio
      in the femur of rat osteoporosis model.
AB  - Resveratrol's effect on bone mineral density (BMD) and expression of cytokines in
      ovariectomized rats (postmenopausal osteoporosis model) was studied. The study
      was conducted on 3-month-old Sprague-Dawley rats that were (a) sham-operated, (b)
      ovariectomized, (c) ovariectomized and treated with beta-estradiol (487.5 ug/kg
      weight/day), and (d) ovariectomized and treated with resveratrol (625 ug/Kg body
      weight/day). The treatment was for 4 weeks. After sacrifice BMD and gene
      expression (RANKL, OPG, IL-23, and IL-17A, IL-1beta, and TNFalpha) were measured
      in tibia and femur respectively. Resveratrol could restore RANKL/OPG ratio,
      slightly increase BMD, and moderately but significantly reduce IL-23, IL-17A, IL
      1beta, and TNF-alpha cytokine expression levels.

PMID- 30239308
TI  - Field evaluation of two commercial RT-rtPCR assays for porcine reproductive and
      respiratory syndrome virus detection using sera from ill and healthy pigs, China.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly
      contagious respiratory virus causing severe morbidity in pigs worldwide. Control
      strategies for PRRSV often rely on detecting PRRSV, culling or isolating sick
      pigs, disinfecting pig barns, vaccination, and monitoring for virus spread. Given
      the high economic impact of PRRSV on pig farms, there is a great need for rapid
      and reliable PRRSV detection assays. We compared the performance of 2 commercial
      reverse-transcription real-time PCR (RT-rtPCR) assays, the VetMAX PRRSV NA and EU
      reagents (ABI assay) and the PRRSV general RT-rtPCR kit (Anheal assay), for the
      molecular detection of PRRSV in sera collected from pigs in China. Between June
      and September 2015, sera were collected from 219 healthy and 104 suspected PRRSV
      infected pigs on 4 farms in China. Employing blinding, the 2 assays were run by 2
      laboratories (Guangzhou Animal Health Inspection Institute [GAHII] and Sun Yat
      sen University [SYSU] laboratories) and compared. Although both assays detected
      PRRSV with 100% specificity at both laboratories, the sensitivity (95% vs. 78% at
      GAHII; 94% vs. 72% at SYSU Laboratory) and the reproducibility (kappa value 0.933
      vs. 0.931) were slightly better for the ABI assay compared to the Anheal assay.

PMID- 30239311
TI  - Management of severe intraoperative hemorrhage during intraventricular
      neuroendoscopic procedures: the dry field technique.
AB  - OBJECTIVE: The unexpected intraoperative intraventricular hemorrhage is a rare
      but feared and life-threatening complication in neuroendoscopic procedures
      because of loss of endoscopic vision. The authors present their experience with
      the so-called "dry field technique" (DFT) for the management of intraventricular
      hemorrhages during purely endoscopic procedures. This technique requires the
      aspiration of the entire intraventricular CSF to achieve clear visualization of
      the bleeding source. METHODS: More than 500 neuroendoscopic intraventricular
      procedures were retrospectively analyzed over the last 24 years for documented
      severe hemorrhages, which were treated by the application of the DFT. RESULTS:
      The technique was required in 6 cases, including tumor resection/biopsy, cyst
      resection, and intraventricular lavage. Additionally, the technique was applied
      as part of the planned strategy in 3 cases of endoscopic tumor removal. The
      hemorrhage was stopped in all cases and no associated postoperative deficits
      occurred. CONCLUSIONS: Although severe hemorrhages are rare, the neurosurgeon
      needs to be aware of them and has to establish strategies for their management.
      Most hemorrhages can be stopped by constant irrigation and coagulation. In the
      other rare cases, the DFT is a safe, reliable technique and can be easily
      incorporated into endoscopic surgery.

PMID- 30239312
TI  - Postcranioplasty seizures following decompressive craniectomy and seizure
      prophylaxis: a retrospective analysis at a single institution.
AB  - OBJECTIVE: Cranioplasty is a relatively simple and less invasive intervention,
      but it is associated with a high incidence of postoperative seizures. The
      incidence of, and the risk factors for, such seizures and the effect of
      prophylactic antiepileptic drugs (AEDs) have not been well studied. The authors'
      aim was to evaluate the risk factors that predispose patients to postcranioplasty
      seizures and to examine the role of seizure prophylaxis in cranioplasty. METHODS:
      The records of patients who had undergone cranioplasty at the authors' medical
      center between 2009 and 2014 with at last 2 years of follow-up were
      retrospectively reviewed. Demographic and clinical characteristics, the
      occurrence of postoperative seizures, and postoperative complications were
      analyzed. RESULTS: Among the 583 patients eligible for inclusion in the study,
      247 had preexisting seizures or used AEDs before the cranioplasty and 336 had no
      seizures prior to cranioplasty. Of these 336 patients, 89 (26.5%) had new-onset
      seizures following cranioplasty. Prophylactic AEDs were administered to 56
      patients for 1 week after cranioplasty. No early seizures occurred in these
      patients, and this finding was statistically significant (p = 0.012). Liver
      cirrhosis, intraoperative blood loss, and shunt-dependent hydrocephalus were risk
      factors for postcranioplasty seizures in the multivariable analysis. CONCLUSIONS:
      Cranioplasty is associated with a high incidence of postoperative seizures. The
      prophylactic use of AEDs can reduce the occurrence of early seizures.

PMID- 30239313
TI  - Vessel wall MRI characteristics of endovascularly treated aneurysms: association
      with angiographic vasospasm.
AB  - OBJECTIVE: The aim of this paper was to evaluate the association between
      intracranial vessel wall MRI enhancement characteristics and the development of
      angiographic vasospasm in endovascularly treated aneurysm patients. METHODS:
      Consecutive cases of both ruptured and unruptured intracranial aneurysms that
      were treated endovascularly, followed by intracranial vessel wall MRI in the
      immediate postoperative period, were included. Two raters blinded to clinical
      data and follow-up imaging independently evaluated for the presence, pattern, and
      intensity of wall enhancement. Development of angiographic vasospasm was
      independently evaluated. Delayed cerebral ischemia; cerebral infarct; procedural
      details; and presence and grade of subarachnoid, parenchymal, and
      intraventricular hemorrhage were evaluated. Statistical associations were
      determined on a per-vessel segment and per-patient basis. RESULTS: Twenty-nine
      patients with 30 treated aneurysms (8 unruptured and 22 ruptured) were included
      in this study. Interobserver agreement was substantial for the presence of
      enhancement (kappa = 0.67) and nearly perfect for distribution (kappa = 0.87) and
      intensity (kappa = 0.84) of wall enhancement. Patients with ruptured aneurysms
      had a significantly greater number of enhancing segments than those with
      unruptured aneurysms (29.9% vs 7.2%; OR 5.5, 95% CI 2.2-13.7). For ruptured
      cases, wall enhancement was significantly associated with subsequent angiographic
      vasospasm while controlling for grade of hemorrhage (adjusted OR 3.9, 95% CI 1.7
      9.4). Vessel segments affected by balloon, stent, or flow-diverter use
      demonstrated greater enhancement than those not affected (OR 22.7, 95% CI 5.3
      97.2 for ruptured; and OR 12.9, 95% CI 3.3-49.8 for unruptured). CONCLUSIONS:
      Vessel wall enhancement after endovascular treatment of ruptured aneurysms is
      associated with subsequent angiographic vasospasm.

PMID- 30239314
TI  - 11C-methionine-18F-FDG dual-PET-tracer-based target delineation of malignant
      glioma: evaluation of its geometrical and clinical features for planning
      radiation therapy.
AB  - OBJECTIVE: It is important to correctly and precisely define the target volume
      for radiotherapy (RT) of malignant glioma. 11C-methionine (MET) positron emission
      tomography (PET) holds promise for detecting areas of glioma cell infiltration:
      the authors' previous research showed that the magnitude of disruption of MET and
      18F-fluorodeoxyglucose (FDG) uptake correlation (decoupling score [DS]) precisely
      reflects glioma cell invasion. The purpose of the present study was to analyze
      volumetric and geometrical properties of RT target delineation based on DS and
      compare them with those based on MRI. METHODS: Twenty-five patients with a
      diagnosis of malignant glioma were included in this study. Three target volumes
      were compared: 1) contrast-enhancing core lesions identified by contrast-enhanced
      T1-weighted images (T1Gd), 2) high-intensity lesions on T2-weighted images, and
      3) lesions showing high DS (DS >= 3; hDS). The geometrical differences of these
      target volumes were assessed by calculating the probabilities of overlap and one
      encompassing the other. The correlation of geometrical features of RT planning
      and recurrence patterns was further analyzed. RESULTS: The analysis revealed that
      T1Gd with a 2.0-cm margin was able to cover the entire high DS area only in 6
      (24%) patients, which indicates that microscopic invasion of glioma cells often
      extended more than 2.0 cm beyond a Gd-enhanced core lesion. Insufficient coverage
      of high DS regions with RT target volumes was suggested to be a risk for out-of
      field recurrence. Higher coverage of hDS by T1Gd with a 2-cm margin (i.e., higher
      values of "[T1Gd + 2 cm]/hDS") had a trend to positively impact overall and
      progression-free survival. Cox regression analysis demonstrated that low coverage
      of hDS by T1Gd with a 2-cm margin was predictive of disease recurrence outside
      the Gd-enhanced core lesion, indicative of out-of-field reoccurrence.
      CONCLUSIONS: The findings of this study indicate that MRI is inadequate for
      target delineation for RT in malignant glioma treatment. Expanding the treated
      margins substantially beyond the MRI-based target volume may reduce the risk of
      undertreatment, but it may also result in unnecessary irradiation of uninvolved
      regions. As MET/FDG PET-DS seems to provide more accurate information for target
      delineation than MRI in malignant glioma treatment, this method should be further
      evaluated on a larger scale.

PMID- 30239315
TI  - Prognostic factors in the surgical treatment of intracanalicular primary optic
      nerve sheath meningiomas.
AB  - OBJECTIVE: Although meningiomas frequently involve the optic nerve, primary optic
      nerve sheath meningiomas (ONSMs) are rare, accounting for only 1% of all
      meningiomas. Given the high risk of vision loss with these tumors, surgical
      intervention is seldom considered, and radiation or observation is commonly
      applied. Here, the authors describe the visual outcomes for a series of patients
      who were treated with surgery aiming at maximal tumor resection and highlight
      their prognostic factors. METHODS: The authors retrospectively analyzed the data
      for 8 patients with intracanalicular ONSMs who had been surgically treated by the
      senior author (O.A.) between 1998 and 2016. Meningiomas extending into the optic
      canal from the intracranial cavity (i.e., clinoid, sphenoid wing, tuberculum
      sellae, diaphragma sellae) were excluded. Diagnosis was based on
      ophthalmological, radiological, and intraoperative findings, which were confirmed
      by the typical histological findings. Preoperative, postoperative, and follow-up
      visual assessments were performed by neuro-ophthalmologists in all cases.
      RESULTS: The patients included 7 females and 1 male. The mean age at diagnosis
      was 45.1 years (range 25.0-70.0 years). Mean duration of follow-up was 38.9
      months (range 3.0-88.0 months). All patients reported visual complaints, and all
      had objective evidence of optic nerve dysfunction. Their evaluation included
      visual field, visual acuity, funduscopy, and retinal fiber thickness. Total
      resection was obtained in 4 cases. Comparing preoperative and postoperative
      visual function revealed that 4 patients had improvement at the last follow-up, 1
      patient had stable vision, and 3 patients had decreased function but none had
      total vision loss. All patients with good preoperative visual acuity maintained
      this status following surgical treatment. There was no surgical mortality or
      infection. Operative complications included binocular diplopia in 4 patients,
      which remitted spontaneously. CONCLUSIONS: Surgery can play a beneficial role in
      the primary treatment of ONSM, especially lesions located in the posterior third
      of the nerve. Total removal can be achieved with vision preservation or
      improvement, without major surgical complications, especially at early stages of
      the disease. Patients with good preoperative vision and CSF flow in the optic
      sheath have better chances of a favorable outcome than those with poor vision.

PMID- 30239316
TI  - Refining the anatomic boundaries of the endoscopic endonasal transpterygoid
      approach: the "VELPPHA area" concept.
AB  - OBJECTIVE: The endoscopic endonasal transpterygoid route has been widely
      evaluated in cadavers, and it is currently used during surgery for specific
      diseases involving the lateral skull base. Identification of the petrous segment
      of the internal carotid artery (ICA) is a key step during this approach, and the
      vidian nerve (VN) has been described as a principal landmark for safe endonasal
      localization of the petrous ICA at the level of the foramen lacerum. However, the
      relationship of the VN to the ICA at this level is complex as well as variable
      and has not been described in the pertinent literature. Accordingly, the authors
      undertook this purely anatomical study to detail and quantify the peri-lacerum
      anatomy as seen via an endoscopic endonasal transpterygoid pathway. METHODS:
      Eight human anatomical specimens (16 sides) were dissected endonasally under
      direct endoscopic visualization. Anatomical landmarks of the VN and the posterior
      end of the vidian canal (VC) during the endoscopic endonasal transpterygoid
      approach were described, quantitative anatomical data were compiled, and a
      schematic classification of the most relevant structures encountered was
      proposed. RESULTS: The endoscopic endonasal transpterygoid approach was used to
      describe the different anatomical structures surrounding the anterior genu of the
      petrous ICA. Five key anatomical structures were identified and described: the
      VN, the eustachian tube, the foramen lacerum, the petroclival fissure, and the
      pharyngobasilar fascia. These structures were specifically quantified and
      summarized in a schematic acronym-VELPPHA-to describe the area. The VELPPHA area
      is a dense fibrocartilaginous space around the inferior compartment of the
      foramen lacerum that can be reached by following the VC posteriorly; this area
      represents the posterior limits of the transpterygoid approach and, of utmost
      importance, no neurovascular structures were observed through the VELPPHA area in
      this study, indicating that it should be a safe zone for surgery in the posterior
      end of the endoscopic endonasal transpterygoid approach. CONCLUSIONS: The VELPPHA
      area represents the posterior limits of the endoscopic endonasal transpterygoid
      approach. Early identification of this area can enhance the safety of the
      endoscopic endonasal transpterygoid approach expanded to the lateral aspect of
      the skull base, especially when treating patients with poorly pneumatized
      sphenoid sinuses.

PMID- 30239318
TI  - Letter to the Editor. Contralateral transmaxillary approach.

PMID- 30239317
TI  - Perioperative outcomes following reoperation for recurrent insular gliomas.
AB  - OBJECTIVE: Greater extent of resection (EOR) improves overall survival and
      progression-free survival for patients with low- and high-grade glioma. While
      resection for newly diagnosed insular gliomas can be performed with minimal
      morbidity, perioperative morbidity is not clearly defined for patients undergoing
      a repeat resection for recurrent insular gliomas. In this study the authors
      report on tumor characteristics, tumor EOR, and functional outcomes in patients
      undergoing reoperation for recurrent insular glioma. METHODS: Adult patients with
      insular gliomas (WHO grades II-IV) who underwent index resection followed by
      reoperation were identified through the University of California San Francisco
      Brain Tumor Center. Treatment history and functional outcomes were collected
      retrospectively from the electronic medical record. Pre- and postoperative tumor
      volumes were quantified using software with region-of-interest analysis based on
      FLAIR and T1-weighted postgadolinium sequences from pre- and postoperative MRI.
      RESULTS: Forty-four patients (63.6% male, 36.4% female) undergoing 49
      reoperations for recurrent insular tumors were identified with a median follow-up
      of 741 days. Left- and right-sided tumors comprised 52.3% and 47.7% of the
      cohort, respectively. WHO grade II, III, and IV gliomas comprised 46.9%, 28.6%,
      and 24.5% of the cohort, respectively. Ninety-five percent (95.9%) of cases
      involved language and/or motor mapping. Median EOR of the insular component of
      grade II, III, and IV tumors were 82.1%, 75.0%, and 94.6%, respectively. EOR
      during reoperation was not impacted by Berger-Sanai insular zone or tumor side.
      At the time of reoperation, 44.9% of tumors demonstrated malignant transformation
      to a higher WHO grade. Ninety-day postoperative assessment confirmed that 91.5%
      of patients had no new postoperative deficit attributable to surgery. Of those
      with new deficits, 3 (6.4%) had a visual field cut and 1 (2.1%) had hemiparesis
      (strength grade 1-2/5). The presence of a new postoperative deficit did not vary
      with EOR. CONCLUSIONS: Recurrent insular gliomas, regardless of insular zone and
      pathology, may be reoperated on with an overall acceptable degree of resection
      and safety despite their anatomical and functional complexities. The use of
      intraoperative mapping utilizing asleep or awake methods may reduce morbidity to
      acceptable rates despite prior surgery.

PMID- 30239319
TI  - Letter to the Editor. PbtO2 and prognosis after decompressive craniectomy.

PMID- 30239320
TI  - Morphological parameters as factors of 12-month neurological worsening in
      surgical treatment of patients with unruptured saccular intracranial aneurysms:
      importance of size ratio.
AB  - OBJECTIVE: It is well known that larger aneurysm size is a risk factor for poor
      outcome after surgical treatment of unruptured saccular intracranial aneurysms
      (USIAs). However, the authors have occasionally observed poor outcome in the
      surgical treatment of small USIAs and hypothesized that size ratio has a negative
      impact on outcome. The aim of this paper was to investigate the influence of size
      ratio on outcome in the surgical treatment of USIAs. METHODS: Prospectively
      collected clinical and radiological data of 683 consecutive patients harboring
      683 surgically treated USIAs were evaluated. Dome-to-neck ratio was defined as
      the ratio of the maximum width of the aneurysm to the average neck diameter. The
      aspect ratio was defined as the ratio of the maximum perpendicular height of the
      aneurysm to the average neck diameter of the aneurysm. The size ratio was
      calculated by dividing the maximum aneurysm diameter (height or width, mm) by the
      average parent artery diameter (mm). Neurological worsening was defined as an
      increase in modified Rankin Scale score of 1 or more points at 12 months.
      Clinical and radiological variables were compared between patients with and
      without neurological worsening. RESULTS: The median patient age was 64 years (IQR
      56-71 years), and 528 (77%) patients were female. The median maximum size, dome
      to-neck ratio, aspect ratio, and size ratio were 4.7 mm (IQR 3.6-6.7 mm), 1.2
      (IQR 1.0-1.4), 1.0 (IQR 0.76-1.3), and 1.9 (IQR 1.4-2.8), respectively. The size
      ratio was significantly correlated with maximum size (r = 0.83, p < 0.0001), dome
      to-neck ratio (r = 0.69, p < 0.0001), and aspect ratio (r = 0.74, p < 0.0001).
      Multivariate logistic regression analysis showed that the specific USIA location
      (paraclinoid segment of the internal carotid artery: OR 6.2, 95% CI 2.6-15, p <
      0.0001; and basilar artery: OR 8.4, 95% CI 2.8-25, p < 0.0001), size ratio (OR
      1.3, 95% CI 1.1-1.6, p = 0.021), and postoperative ischemic lesion (OR 9.4, 95%
      CI 4.4-19, p < 0.0001) were associated with neurological worsening (n = 52,
      7.6%), and other characteristics showed no significant differences. CONCLUSIONS:
      The present study showed that size ratio, and not other morphological parameters,
      was a risk factor for 12-month neurological worsening in surgically treated
      patients with USIAs. The size ratio should be further studied in a large,
      prospective observational cohort to predict neurological worsening in the
      surgical treatment of USIAs.

PMID- 30239321
TI  - Machine learning ensemble models predict total charges and drivers of cost for
      transsphenoidal surgery for pituitary tumor.
AB  - OBJECTIVE: Efficient allocation of resources in the healthcare system enables
      providers to care for more and needier patients. Identifying drivers of total
      charges for transsphenoidal surgery (TSS) for pituitary tumors, which are poorly
      understood, represents an opportunity for neurosurgeons to reduce waste and
      provide higher-quality care for their patients. In this study the authors used a
      large, national database to build machine learning (ML) ensembles that directly
      predict total charges in this patient population. They then interrogated the
      ensembles to identify variables that predict high charges. METHODS: The authors
      created a training data set of 15,487 patients who underwent TSS between 2002 and
      2011 and were registered in the National Inpatient Sample. Thirty-two ML
      algorithms were trained to predict total charges from 71 collected variables, and
      the most predictive algorithms combined to form an ensemble model. The model was
      internally and externally validated to demonstrate generalizability. Permutation
      importance and partial dependence analyses were performed to identify the
      strongest drivers of total charges. Given the overwhelming influence of length of
      stay (LOS), a second ensemble excluding LOS as a predictor was built to identify
      additional drivers of total charges. RESULTS: An ensemble model comprising 3
      gradient boosted tree classifiers best predicted total charges (root mean square
      logarithmic error = 0.446; 95% CI 0.439-0.453; holdout = 0.455). LOS was by far
      the strongest predictor of total charges, increasing total predicted charges by
      approximately $5000 per day. In the absence of LOS, the strongest predictors of
      total charges were admission type, hospital region, race, any postoperative
      complication, and hospital ownership type. CONCLUSIONS: ML ensembles predict
      total charges for TSS with good fidelity. The authors identified extended LOS,
      nonelective admission type, non-Southern hospital region, minority race,
      postoperative complication, and private investor hospital ownership as drivers of
      total charges and potential targets for cost-lowering interventions.

PMID- 30239322
TI  - A single case of MRI-guided focused ultrasound ventro-oral thalamotomy for
      musician's dystonia.
AB  - Musician's dystonia (MD) is a type of focal hand dystonia that develops only
      while playing musical instruments and interferes with skilled and fine movements.
      Lesioning of the ventro-oral (Vo) nucleus of the thalamus (Vo-thalamotomy) using
      radiofrequency can cause dramatic improvement in MD symptoms. Focused ultrasound
      (FUS) can make intracranial focal lesions without an incision. The authors used
      MRI-guided FUS (MRgFUS) to create a lesion on the Vo nucleus to treat a patient
      with MD. Tubiana's MD scale (TMDS) was used to evaluate the condition of musical
      play ranging from 1 to 5 (1: worst, 5: best). The patient was a 35-year-old right
      handed man with involuntary flexion of the right second, third, and fourth
      fingers, which occurred while playing a classical guitar. Immediately after
      therapeutic sonications of FUS Vo-thalamotomy, there was dramatic improvement in
      the MD symptoms. The TMDS scores before; at 0 and 1 week after; and at 1, 3, 6,
      and 12 months after MRgFUS Vo-thalamotomy were 1, 4, 4, 5, 5, 5, and 5,
      respectively. No complications were observed. Focused ultrasound Vo-thalamotomy
      can be an effective treatment for MD.

PMID- 30239323
TI  - Letter to the Editor. Intracranial stenting in acute stroke.

PMID- 30239324
TI  - Development of a multiplex real-time PCR assay using two thermocycling platforms
      for detection of major bacterial pathogens associated with bovine respiratory
      disease complex from clinical samples.
AB  - Bovine respiratory disease complex (BRDC) is one of the most significant diseases
      of cattle. Bacterial pathogens involved in BRDC include Mannheimia haemolytica,
      Mycoplasma bovis, Histophilus somni, and Pasteurella multocida. We developed and
      evaluated a multiplexed real-time hydrolysis probe (rtPCR) assay using block
      based Peltier and rotary-based thermocycling on lung tissue, nasal swabs, and
      deep nasopharyngeal swabs. The rtPCR results were compared to culture or a gel
      based M. bovis PCR using statistical analysis to determine optimum quantification
      cycle (Cq) cutoffs to maximize agreement. The limits of detection were 1.2-12
      CFU/reaction for each pathogen. M. haemolytica was the most prevalent organism
      detected by rtPCR, and was most frequently found with P. multocida. The rtPCR
      assay enabled enhanced levels of detection over culture for all pathogens on both
      thermocycling platforms. The rotary-based thermocycler had significantly lower Cq
      cutoffs (35.2 vs. 39.7), which maximized agreement with gold standard culture or
      gel-based PCR results following receiver operating characteristic analysis to
      maximize sensitivity (Se) and specificity (Sp). However, overall assay Se and Sp
      were similar on both platforms (80.5% Se, 88.8% Sp vs. 80.1% Se, 88.3% Sp).
      Implementation of these tests could enhance the detection of these pathogens, and
      with high-throughput workflows could reduce assay time and provide more rapid
      results. The assays may be especially valuable in identifying coinfections, given
      that many more antemortem samples tested in our study were positive for 2 or more
      pathogens by rtPCR ( n = 125) than were detected using culture alone ( n = 25).

PMID- 30239325
TI  - Assessing ototoxicity due to chronic lead and cadmium intake with and without
      noise exposure in the mature mouse.
AB  - Exposure to heavy metals may lead to hearing impairment. However, experimental
      studies have not explored this issue with and without noise exposure in mature
      animals with environmentally relevant doses. The aim of this study was to
      investigate ototoxicity produced by lead (Pb) and cadmium (Cd) and noise, singly
      and in combination, in the adult CBA/CaJ mouse. Metals were delivered via
      drinking water (0.03 mM, 1 mM, and 3 mM Pb; or 30, 100, and 300 MUM Cd) for 12
      weeks, resulting in environmentally- and occupationally relevant mean (+/-
      standard deviations) blood levels of Pb (2.89 +/- 0.44, 38.5 +/- 4.9, and 60.1 +/
      6.6 MUg/dl, respectively) and Cd (1.3 +/- 0.23, 6.37 +/- 0.87, 27.2 +/- 4.1
      MUg/L, respectively). Metal treatment was also combined with a noise exposure
      consisting of a 105 dB broadband (2-20 kHz) stimulus for 2 hr or a sham exposure.
      Auditory performance was determined by comparing auditory brainstem responses
      (ABR) and distortion product otoacoustic emissions (DPOAE) at baseline and after
      11 weeks of metal treatment. Metal-exposed animals did not develop significant
      auditory deficits and did not exhibit morphological damage to cochlear hair
      cells. In contrast, noise-exposed animals, including those exposed to
      combinations of metals and noise, demonstrated significant hair cell loss,
      reduced DPOAE amplitudes, and ABR threshold shifts of 42.2 +/- 13 dB at 32 kHz
      (105 dB noise alone). No significant potentiation or synergistic effects were
      found in groups exposed to multiple agents. This study establishes a highly
      reproducible adult mouse model that may be used to evaluate a variety of
      environmental exposure mixtures.

PMID- 30239326
TI  - Characterization of food waste from different sources in Hong Kong.
AB  - Food waste from different sources or at different generation stages may have
      different compositional characteristics and is therefore suitable for recycling
      into different products. To have a better understanding of their chemical
      composition, five food waste types were collected, namely, household kitchen
      waste (HH), preconsumption and postconsumption food waste from a hotel (Hpr and
      Hpo), wet market food waste (WM) and kitchen waste from a Chinese restaurant
      (CR), and their compositions were assessed monthly for 1 year. They served as
      suitable feedstock for various conversion technologies according to their
      chemical profiles. HH and CR had higher crude protein content (26%) and
      considerable amounts of minerals, making them nutritionally suitable for feeding
      animals. Preconsumption food wastes Hpr and WM had more favorable C:N ratios
      (16.5-17.4) and crude fat contents (4.6-6.5%) as feedstock for composting.
      Postconsumption food wastes were potential feedstock for the production of biogas
      and biodiesel because of the higher dry matter (>26%) and fat content (>13%). The
      coefficients of variation (CV) in all nutrients analyzed except Ca for
      postconsumption food wastes ranged from 5% to 37%, which showed lower temporal
      variability than preconsumption food wastes (CVs 10-131%). This implies that the
      composition of postconsumption food waste was relatively less fluctuating and can
      be considered a more reliable feedstock for food waste conversion. Implications:
      Characterization of food waste composition from different sources and
      determination of their temporal variation were performed to understand their
      characteristics and facilitate sound food waste management. Separating food
      wastes according to their sources and types helps reduce their composition
      variability, and thus increases the consistence in food-waste-derived products
      and recycling success. Study on temporal variation indicates that postconsumption
      food wastes varied less with time and could serve as reliable feedstocks for food
      waste conversion.

PMID- 30239327
TI  - Long-acting reversible contraception: Assessment of knowledge and interest among
      college females.
AB  - OBJECTIVE: To implement the Long-Acting Reversible Contraception Quality
      Improvement (LARC QI) project using evidence-based contraceptive counseling
      techniques to improve knowledge and intent to use among college females.
      PARTICIPANTS: The project, conducted from April through September 2017, involved
      41 female students, from a 4-year public college in North Carolina. METHODS:
      Students participated in group educational sessions on all methods of birth
      control with an emphasis on LARC. Surveys were administered to group participants
      and descriptive statistics were used to determine the difference in knowledge
      scores and intent to use. Descriptive and qualitative analysis described usage of
      LARC methods. RESULTS: LARC knowledge scores significantly improved. Intention to
      use also increased compared to reported actual use. The final chart review
      demonstrated an increase usage of the subdermal implant, but no change for
      intrauterine device. CONCLUSIONS: The college setting offers a unique opportunity
      to use evidence-based contraceptive counseling techniques to guide use of LARC.

PMID- 30239328
TI  - Pseudoruegeria insulae sp. nov., isolated from a tidal flat.
AB  - A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial
      strain, designated BPTF-M20T, was isolated from tidal flat sediment in the Yellow
      Sea, Republic of Korea. Strain BPTF-M20T grew optimally at 30  degrees C, at pH
      7.0-8.0 and in the presence of 2.0-3.0 % (w/v) NaCl. A neighbour-joining
      phylogenetic tree of 16S rRNA gene sequences showed that strain BPTF-M20T fell
      within the clade comprising the type strains of Pseudoruegeria species. Strain
      BPTF-M20T exhibited 16S rRNA gene sequence similarity values of 97.4-98.3 % to
      the type strains of Pseudoruegeria haliotis, Pseudoruegeria lutimaris,
      'Pseudoruegeria litorisediminis' and Pseudoruegeria sabulilitoris and 96.4-96.9 %
      to the type strains of the other Pseudoruegeria species. Strain BPTF-M20T
      contained Q-10 as the predominant ubiquinone and C18 : 1omega7c as the major
      fatty acid. The major polar lipids detected in strain BPTF-M20T were
      phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, one
      unidentified aminolipid and one unidentified glycolipid. The DNA G+C content of
      strain BPTF-M20T was 63.2 mol%. Mean DNA-DNA relatedness values of strain BPTF
      M20T with the type strains of P. haliotis, P. lutimaris, P. sabulilitoris and 'P.
      litorisediminis' were 18-27 %. Differential phenotypic properties, together with
      the phylogenetic and genetic data, revealed that strain BPTF-M20T was separated
      from recognized Pseudoruegeria species. On the basis of the data presented here,
      strain BPTF-M20T is considered to represent a novel species of the genus
      Pseudoruegeria, for which the name Pseudoruegeriainsulae sp. nov. is proposed.
      The type strain is BPTF-M20T (=KACC 19614T=KCTC 62422T=NBRC 113188T).

PMID- 30239329
TI  - Determination and genome-wide analysis of Epstein-Barr virus (EBV) sequences in
      EBV-associated gastric carcinoma from Guangdong, an endemic area of
      nasopharyngeal carcinoma.
AB  - About 10 % of gastric carcinoma worldwide is associated with EBV, which is
      defined as EBV-associated gastric carcinoma (EBVaGC). To date, EBV sequence data
      from EBVaGC in Guangdong, China, an endemic area of nasopharyngeal carcinoma
      (NPC), are not available. In the present study, two EBV genomes from EBVaGC
      specimens from Guangdong (designated as GDGC1 and GDGC2) were determined by next
      generation sequencing, de novo assembly and joining of contigs by Sanger
      sequencing. In addition, we sequenced EBV from two Korean EBVaGC cell lines,
      YCCEL1 and SNU-719. Genomic diversity, including single nucleotide polymorphisms
      (SNPs) and insertions and deletions (indels), phylogenetic analysis and rates of
      protein evolution, was performed using bioinformatics software. The four gastric
      carcinoma-derived EBV (GC-EBV) were all type I. Compared with the reference EBV
      genome, a total of 1815 SNPs (146 indels), 1519 SNPs (106 indels), 1812 SNPs (126
      indels) and 1484 SNPs (106 indels) were found in GDGC1, GDGC2, YCCEL1 and SNU
      719, respectively. These variations were distributed across the entire genome,
      especially in latent genes. In contrast, the sequences of promoters and non
      coding RNAs were strictly conserved. Phylogenetic analyses suggested the presence
      of at least two parental lineages of EBV among the GC-EBV genomes. Rates of
      protein evolution analyses showed that lytic genes were under purifying
      selection; in contrast, latency genes were under positive selection. In
      conclusion, this study determined the EBV genomes in EBVaGC from Guangdong and
      performed a detailed genome-wide analysis of GC-EBV, which would be helpful for
      further understanding of the relationship between EBV genomic variation and
      EBVaGC carcinogenesis.

PMID- 30239330
TI  - Pectobacterium punjabense sp. nov., isolated from blackleg symptoms of potato
      plants in Pakistan.
AB  - Pectobacterium isolates SS95T, SS54 and SS56 were collected from a potato field
      in the Chiniot district in the plains of the Punjab province, Pakistan.
      Sequencing of the gapA barcode revealed that these strains belong to a novel
      phylogenetic group separated from P.ectobacterium wasabiae and Pectobacterium
      parmentieri species. Furthermore, multilocus sequence analyses of 13 housekeeping
      genes (fusA, rpoD, acnA, purA, gyrB, recA, mdh, mtlD, groEL, secY, glyA, gapA and
      rplB) clearly distinguished the type strain, SS95T, from its closest relatives,
      i.e. P. parmentieri RNS 08-42-1AT and P. wasabiae CFBP3304T, as well as from all
      the other known Pectobacteriumspecies. In silico DNA-DNA hybridization (<44.1 %)
      and average nucleotide identity (<90.75 %) values of strain SS95T compared with
      other Pectobacterium type strains supported the delineation of a new species.
      Genomic and phenotypic comparisons permitted the identification of additional
      traits that distinguished the Pakistani isolates from all other known
      Pectobacterium type strains. The name Pectobacterium punjabense sp. nov. is
      proposed for this taxon with the type strain SS95T (=CFBP 8604T=LMG 30622T).

PMID- 30239331
TI  - Potato purple top disease associated with the novel subgroup 16SrII-X
      phytoplasma.
AB  - Potato (Solanum tuberosum) is a very economically important perennial tuberous
      crop in Saudi Arabia. Potato plants displaying symptoms associated with potato
      purple top disease, such as aerial tubers and purple and small leaves, were
      observed in Al-Bukairiyah, Fowlq and Buraydah, Al-Tarafiyah, Qassim governorate,
      Saudi Arabia. In this study, we examined samples taken from 12 symptomatic potato
      plants and confirmed the presence of phytoplasma DNA. Analysis of the 16S rRNA
      encoding sequences revealed that the symptomatic plants were infected with
      phytoplasma belonging to the peanut witches'-broom group (16SrII). Sequencing of
      the 16S rRNA- encoding gene, computer-simulated RFLP analysis and phylogenetic
      analysis revealed the presence of a novel representative of the 16SrII-X
      subgroup. The present study identified potato plants as a novel host for novel
      phytoplasma strains belonging to the pigeon pea witches'-broom group in Saudi
      Arabia.

PMID- 30239333
TI  - Compression mechanisms of ferroelectric PbTiO3 via high pressure neutron
      scattering.
AB  - Switchable atomic displacements generate electric dipole moments in ferroelectric
      materials utilized in many contemporary devices. Lead titanate, a perovskite
      oxide with formula PbTiO3, has been referred to as a textbook example of a
      prototype displacive ferroelectric and is a testing platform of widely used
      models of piezoelectric response of complex solid-solutions. PbTiO3 has been
      addressed by experimental and computational studies, often with apparently
      conflicting conclusions. To date, hydrostatic pressure experiments have been
      interpreted in terms of a model in which the dipole moments gradually diminish
      with increasing pressure until a transition to a cubic phase, characterized by a
      zero average dipole moment, occurs. The model unrealistically assumes an even
      compression of the crystal. Here we show by high-pressure neutron powder
      diffraction measurements that a fast and slow shrinkage of 12-oxygen cages around
      Pb and octahedra around Ti, respectively, takes place. A phase diagram
      consolidating earlier and present results is given.

PMID- 30239334
TI  - Probing non-locality of interactions in a Bose-Einstein condensate using
      solitons.
AB  - We consider a Bose-Einstein condensate (BEC) with non-local inter-particle
      interactions. The local Gross-Pitaevskii (GP) equation is valid for the gas
      parameter [Formula: see text], but for [Formula: see text], the BEC is described
      by a modified GP equation (MGPE). We study the exact solutions of the MGPE
      describing bright and dark solitons. It turns out that the width of these non
      local solitons has qualitatively similar behaviour as the modified healing length
      due to the non-local interactions of the MGPE. We also study the effect of the
      non-locality and gas parameter (nu) on the stability of the solitons using the
      Vakhitov-Kolokolov (VK) stability criterion. We show that these soliton solutions
      are stable according to the VK criterion. Further, the stability of these soliton
      solutions gets enhanced due to the non-locality of interactions.

PMID- 30239335
TI  - Ab initio computer simulations of non-equilibrium radiation-induced cascades in
      amorphous Ge2Sb2Te5.
AB  - Ion irradiation corresponds to a process that involves the production of non
      equilibrium cascades in the host material, and the atomistic modelling of such
      events in glasses is challenging. Here, non-equilibrium cascades in amorphous
      Ge2Sb2Te5 phase-change memory material have been investigated by means of first
      principles molecular-dynamics simulations. A stochastic boundary-conditions
      approach is employed to treat the thermal nature of the cascades and drive the
      modelled system back to equilibrium in a natural way, while four different
      initial thermal-spike energies are considered. A comprehensive analysis of the
      cascade evolution is presented with respect to the kinetic profile and the
      dynamics of the cascade inside the glass structure. The modelling results show
      that the instantaneous maximum kinetic energy decays rapidly with time, and that
      the time-scale of the ballistic phase of the cascade inside the glass model is
      very short. The quality of the implemented approach is validated through a
      comparison of the calculated structure factor for the modelled glasses with
      experimental data from the literature. Analysis of the bonding for all the
      species in the glass structure highlights particular structural modifications in
      the connectivity of the amorphous network due to the simulated cascade.

PMID- 30239332
TI  - Neuroprotective effects of TRPA1 channels in the cerebral endothelium following
      ischemic stroke.
AB  - Hypoxia and ischemia are linked to oxidative stress, which can activate the
      oxidant-sensitive transient receptor potential ankyrin 1 (TRPA1) channel in
      cerebral artery endothelial cells, leading to vasodilation. We hypothesized that
      TRPA1 channels in endothelial cells are activated by hypoxia-derived reactive
      oxygen species, leading to cerebral artery dilation and reduced ischemic damage.
      Using isolated cerebral arteries expressing a Ca2+ biosensor in endothelial
      cells, we show that 4-hydroxynonenal and hypoxia increased TRPA1 activity,
      detected as TRPA1 sparklets. TRPA1 activity during hypoxia was blocked by
      antioxidants and by TRPA1 antagonism. Hypoxia caused dilation of cerebral
      arteries, which was disrupted by antioxidants, TRPA1 blockade and by endothelial
      cell-specific Trpa1 deletion (Trpa1 ecKO mice). Loss of TRPA1 channels in
      endothelial cells increased cerebral infarcts, whereas TRPA1 activation with
      cinnamaldehyde reduced infarct in wildtype, but not Trpa1 ecKO, mice. These data
      suggest that endothelial TRPA1 channels are sensors of hypoxia leading to
      vasodilation, thereby reducing ischemic damage.

PMID- 30239336
TI  - A simulation study of BrachyShade, a shadow-based internal source tracking system
      for HDR prostate brachytherapy.
AB  - This paper presents a simulation study of BrachyShade, a proposed internal source
      tracking system for real time quality assurance in high dose rate prostate
      brachytherapy. BrachyShade consists of a set of spherical tungsten occluders
      located above a pixellated silicon photodetector. The source location is
      estimated by minimising the mean squared error between a parametric model of the
      shadow image and acquired images of the shadows projected on the detector plane.
      A novel algorithm is finally employed to correct the systemic error resulting
      from Compton scattering in the medium. The worst-case error obtained with
      BrachyShade for a 13.5 ms image acquisition is less than 1.3 mm in the most
      distant part of the treatment volume, while for 75% of source locations an error
      of less than 0.42 mm was achieved.

PMID- 30239337
TI  - Spin-polarized resonant surface state in (1 1 1) Sm1-x Gd x Al2, a zero
      magnetization ferromagnet.
AB  - The electronic structure of (1 1 1) Sm1-x Gd x Al2, a zero-magnetization
      ferromagnet, is investigated by angle- and spin- resolved photoemission
      spectroscopy. An intense electron pocket strongly localized around [Formula: see
      text] and close to the Fermi level is observed and analyzed in detail. Its
      various characteristics, combined with electronic structure calculations, reveal
      a resonant surface state of 5d character and Lambda1 symmetry, likely built on
      bulk states developing around L points. It exhibits moreover a low temperature
      positive spin polarization at the Fermi level, of strong interest for spin
      dependent transport properties in Sm1-x Gd x Al2-based spintronic devices.

PMID- 30239338
TI  - Multistep coupling of preexisting local ferroic distortions in PbTiO3 above the
      Curie temperature.
AB  - Temperature-dependent Raman spectroscopic analyses were performed for the
      prominent ferroelectric PbTiO3 in the temperature range 130-1040 K, focusing
      particularly on its paraelectric state above the Curie temperature [Formula: see
      text] K. The temperature evolution of the anomalous Raman scattering reveals that
      not only local ferroic distortions persist at temperatures well above [Formula:
      see text], but also there is a sequence of different coupling processes preceding
      the appearance of long-range ferroelectric order at [Formula: see text]. Our
      results indicate that, similar to relaxor ferroelectrics, the paraelectric phase
      of PbTiO3 can be considered as an ergodic system of local ferroic distortions,
      which only on average appears to have cubic symmetry.

PMID- 30239339
TI  - Isoflavones and bone health in perimenopausal and postmenopausal women.
AB  - PURPOSE OF REVIEW: Isoflavones exert estrogenic activity distinct from estrogen,
      they have the potential to treat diseases and symptoms related to estrogen
      deficiency with minimal side effects and risks. Isoflavone supplementation, in
      general, is shown to exert beneficial effects against estrogen-deficient bone
      loss in women, however, some clinical trials still produce conflicting findings.
      The purpose of this review is to highlight and summarize the most recent and up
      to-date research in the field and to bring attention to factors that play a major
      role in the outcomes of clinical trials that investigate phytoestrogens. Here, we
      also discuss the latest and most relevant data regarding the clinical safety of
      these substances. RECENT FINDINGS: Isoflavones are naturally occurring secondary
      metabolites found in the Fabacaea plant family. Clinical data from isoflavone
      interventions support that aglycones (abundant in fermented products) exert
      enhanced beneficial effects against estrogen-deficient bone loss in women
      compared with isoflavone glycosides. Studies that employ methods to determine
      isoflavone content and form of treatments are more likely detect beneficial
      effects on bone. EFSA have confirmed the safety of isoflavones for women in the
      most comprehensive report to date. SUMMARY: Isoflavone aglycones exert greater
      effects against bone loss than glycosides. Isoflavones show promise as a first
      line prophylactic/treatment for bone loss in women.

PMID- 30239340
TI  - Dietary supplement intake among the elderly: hazards and benefits.
AB  - PURPOSE OF REVIEW: A large percentage of older adults do not receive recommended
      amounts of many nutrients from food alone. Accordingly, the routine use of
      dietary supplements has become common among older persons. Although supplement
      use provides potential benefits by increasing nutrient intakes, there are
      potential drawbacks. RECENT FINDINGS: Clinical studies have pointed to potential
      reductions in the risk to develop age-related diseases among older people who
      reported long-term use of multivitamin supplements. Higher plasma levels of omega
      3 polyunsaturated fatty acids were also associated with fewer cardiovascular
      deaths in older people consuming omega-3 supplements. Dietary protein
      supplementation combined with exercise had a strong effect in preventing age
      related muscle mass attenuation and leg strength loss in older people. Finally,
      beneficial effects of purified flavonoids on cognitive functions have been
      reported in some studies, whereas in a significant number of other studies, no
      such effect could be observed. SUMMARY: The use of dietary supplements among
      older people has increased over the years due to the expectation of reducing the
      risk of developing chronic diseases. Although some dietary supplements may indeed
      fulfill some of these expectations, it would be unwise to assume that they are
      all efficacious and safe to use.

PMID- 30239341
TI  - Trastuzumab-Associated Dermatomyositis.

PMID- 30239342
TI  - Evolving techniques for endoscopic retrograde cholangiopancreatography in gastric
      bypass patients.
AB  - PURPOSE OF REVIEW: The present review describes the current and evolving
      techniques available in approaching endoscopic retrograde
      cholangiopancreatography (ERCP) for patients with Roux-en-Y gastric bypass (RYGB)
      anatomy. RECENT FINDINGS: Recent studies have demonstrated that device-assisted
      enteroscopy (DAE) approaches have high failures rates when performing ERCP, but
      are currently considered the first-line approach for patients with RYGB anatomy
      because of lower costs and risks compared to surgery. In contrast, laparoscopicy
      assisted-ERCP (LA-ERCP) exhibits high technical success rates but carries
      surgical risks and requires a high degree of scheduling coordination. A novel,
      completely endoscopic approach called endoscopic ultrasound directed transgastric
      ERCP (EDGE), also known as gastric access temporary for endoscopy (GATE), has in
      recent years shown high ERCP success rates comparable to LA-ERCPs while obviating
      the need for surgical assistance. SUMMARY: ERCP is technically difficult in
      patients with RYGB anatomy. Numerous approaches to ERCP exist, although
      availability of these techniques may be limited and depend on institutional
      expertise. The best initial approach should be considered based on patient
      history and institutional factors.

PMID- 30239343
TI  - Macrophage interactions with fungi and bacteria in inflammatory bowel disease.
AB  - PURPOSE OF REVIEW: In this review, we discuss recent advances into delineating
      the dual role of intestinal phagocytes in health and during intestinal disease.
      We further discuss the key role of gut-resident macrophages in recognition of
      bacterial and fungal microbiota in the gut. RECENT FINDINGS: Inflammatory bowel
      disease (IBD) commonly manifests with pathologic changes in the composition of
      gut bacterial and fungal microbiota. Intestinal macrophages are key regulators of
      the balance between tolerogenic immunity and inflammation. Recent studies have
      highlighted the role of resident intestinal macrophages in the control of
      commensal fungi and bacteria in the steady state and during dysbiosis. The dual
      role of these cells in maintaining intestinal homeostasis and responding to
      microbiota dysbiosis during inflammation is being increasingly studied. SUMMARY:
      It is becoming increasingly clear that an aberrant proinflammatory response to
      microbiota by infiltrating monocytes plays a role in the development of
      intestinal inflammation. Intestinal mononuclear phagocytes with characteristics
      of macrophages play an important role in limiting fungal and bacterial overgrowth
      under these conditions, but can be influenced by the inflammatory environment to
      further propel inflammation. Better understanding of the interaction of
      intestinal macrophages with host microbiota including commensal fungi and
      bacteria, provides an opportunity for the development of more targeted therapies
      for IBD.

PMID- 30239344
TI  - Updates in mucosal immunology for inflammatory bowel diseases.

PMID- 30239345
TI  - Opioid Pain Medication Use in New Urogynecology Patients.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of opioid pain
      medication use among patients presenting for a new visit to the urogynecology
      clinic compared with those presenting to general gynecology. METHODS: We
      identified all patients who presented for new patient visits to the urogynecology
      and gynecology clinics between January 1, 2016, and December 31, 2016. Any
      previous or current opioid use was extracted from the electronic medical record
      medication list. Statistical analysis was performed using chi and Fisher exact
      tests for comparisons of categorical variables. Modified Poisson regression
      models were used to estimate prevalence proportion ratios (PPRs). RESULTS: There
      were 1835 (955 gynecology, 880 urogynecology) patients included. Median age was
      47 years (interquartile range, 29 years), and median body mass index was 28.15
      kg/m (interquartile range, 9.96 kg/m). Prevalence of opioid use was lowest among
      women who identified as Asian or other race and highest among black and Native
      American women; however, when compared by ethnicity, use was lowest among
      Hispanic women (P = 0.01). Among new urogynecology patients, 14% had self
      reported opioid pain medication usage. Opioid use was almost twice as likely in
      the urogynecology group (PPR, 1.86; 95% confidence interval, 1.4-2.4). When
      adjusted for confounders, the urogynecology group was 1.3 times as likely to
      report opioid use (PPR 1.29; 95% confidence interval, 1.0-1.8), with this result
      approaching statistical significance. CONCLUSIONS: Opioid use is greater in
      patients presenting to the urogynecology clinic compared with general gynecology.
      Urogynecologists need to know this information for planning and optimizing pain
      management in this population.

PMID- 30239346
TI  - A Hypothesis Generating the Mechanical Systems Underlying Posterior Vaginal
      Prolapse Based on Observed Displacements by Dynamic Magnetic Resonance Imaging.
AB  - OBJECTIVE: The aim of this study was to analyze quantified displacements of the
      posterior vaginal wall (PVW) on dynamic magnetic resonance imaging (MRI), which
      may generate hypotheses for the detailed mechanisms that underlie the development
      of posterior vaginal prolapse. METHODS: Pelvic dynamic MRI scans were obtained
      for 12 women with normal vaginal structure (stage 0) and 62 women with 4
      consecutive stages (1-4) of posterior vaginal prolapse. Structural locations
      (apex vagina, distal vagina, and mid-perineal body [PB]) and equidistant points
      along the PVW (points 4-6 were considered as midvagina) were identified, and PVW
      length, straight distance of PVW, levator ani parameters (levator hiatus length
      [LHL], levator hiatus width [LHW], levator plate angle, anorectal angle, and M
      line [ML]), urogenital hiatus, and prolapse diameter were measured at rest and
      maximal Valsalva, respectively. The displacement of these measurements was
      obtained. RESULTS: From stage 0 to 2, the variables LHL, LHW, levator plate
      angle, anorectal angle, and ML increased gradually, but midvagina, distal vagina,
      and mid-PB were the opposite. From stage 2 to 3, apex vagina, midvagina, distal
      vaginal, mid-PB, LHL, LHW, and ML raised rapidly and peaked at stage 3, then
      declined at stage 4. In addition, the correlation coefficients between each
      measurement from stage 2 to 3 were statistically higher than those from stage 0
      to 2. CONCLUSIONS: Quantified displacements of the PVW and its supporting
      structure were shown on dynamic MRI, and the mechanical mechanisms were
      hypothesized regarding the interaction between pressure and the support force
      contributing to the deformation of the PVW and the supporting structures.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.

PMID- 30239347
TI  - Different kinetics of liver stiffness using shear wave elastography in patients
      with chronic hepatitis C infection treated with interferon-free regimens.
AB  - BACKGROUND: Direct-acting antivirals (DAAs) lead to a high rate of sustained
      virologic response (SVR) in chronic hepatitis C infection. The aim was to
      evaluate liver stiffness kinetics, using acoustic radiation force impulse (ARFI)
      imaging elastography, during and after DAAs in patients who had reached SVR.
      PATIENTS AND METHODS: A total of 275 consecutive chronic hepatitis C virus
      infected patients were included in this longitudinal prospective single-centre
      study. All patients received DAAs for 8 to 24 weeks, and liver stiffness
      measurements (LSMs) by ARFI at baseline, at week 4, week 12, week 24, and 24
      weeks (SVR24) and 48 weeks (FU48) after the end of treatment were recorded.
      Transient elastography was performed at baseline and at SVR24. RESULTS: A
      decrease in LSM was detected at SVR24 by ARFI and transient elastography (P<0.001
      and <0.001, respectively). A continuous gradual decrease in ARFI was observed in
      patients with cirrhosis versus a nonsignificant change in patients without
      cirrhosis until FU48 (P<0.001 vs. 0.877, respectively). At SVR24, higher baseline
      ARFI values (P=0.038) were associated with a decrease in LSM in patients with
      cirrhosis versus normal international normalization ratio (P=0.003), lower
      bilirubin (P=0.003), and higher albumin (P=0.007) in patients without cirrhosis.
      The incidence of liver stiffness decrease from baseline was higher in patients
      with cirrhosis than in those without cirrhosis (P<0.001), whereas the incidence
      of liver stiffness progression was more pronounced in advanced than in
      compensated cirrhosis (P<0.001). CONCLUSION: After DAAs in patients with SVR,
      liver stiffness improves in patients with cirrhosis, whereas non-cirrhotic
      patients show no true change in liver stiffness. Liver stiffness worsens in
      patients with advanced liver disease.

PMID- 30239348
TI  - Ventricular fibrillation recorded and analysed within an area the size of a
      mobile phone: could it enable cardiac arrest recognition?
AB  - BACKGROUND: Recognition of out-of-hospital-cardiac arrests (OHCAs) at emergency
      medical communication centres is based on questions of OHCA symptoms, resulting
      in 50-80% accuracy rates. However, OHCAs might be recognized more promptly using
      'rhythm-based' recognition, whereby a victim's cardiac rhythm is recorded with
      mobile phone technology that analyses and transmits recordings to emergency
      medical communication centres for further interpretation. OBJECTIVE: To examine
      whether the quality of normal cardiac rhythm and the rhythm with the best
      prognosis in OHCA, ventricular fibrillation (VF), is sufficient for 'rhythm
      based' OHCA recognition when recorded within a mobile phone-sized device.
      PATIENTS AND METHODS: mid-sternum within an area the size of a mobile phone and
      analysed by automated external defibrillator (AED) software and two
      cardiologists. The rhythms were categorized as shockable or nonshockable. The
      cardiologists assessed the quality of the recordings. RESULTS: The AED software
      correctly analysed all normal rhythms and 15 of 22 VF rhythms. The VF duration
      was too short for automatic detection in seven cases. The cardiologists analysed
      all the normal rhythms and VF sequences correctly and graded them as high
      quality. CONCLUSION: The recordings of normal ECG rhythm and VF within an area
      the size of a mobile phone are of sufficient quality and could be used in 'rhythm
      based' OHCA recognition. The VF period was too short for an accurate analysis by
      the AED software in some cases.

PMID- 30239349
TI  - Peculiar clinicopathological features of immune-mediated necrotizing myopathies.
AB  - PURPOSE OF REVIEW: In the past decade, immune-mediated necrotizing myopathies
      have emerged as a separate entity in the heterogenous group of autoimmune
      myopathies. This group is characterized by clinical manifestations restricted to
      the muscle tissue, and until recently, the definition was based on muscular
      pathological features. RECENT FINDINGS: It was shown that they are the most
      severe autoimmune myopathies in term of muscle damages. They have been associated
      with two myositis-specific antibodies: either anti-signal recognition particle
      (anti-SRP) or anti-hydroxy-3-methylglutaryl-CoA reductase (anti-HMGCR)
      antibodies. These two antibodies are now considered as immune-mediated
      necrotizing myopathy (IMNM) diagnostic criteria. Each antibody delineates a
      homogenous subgroup of IMNM patients in terms of severity and IMNM without
      myositis-specific antibodies have a high risk of malignancy. In addition,
      pathological observations as well as in-vitro experiments suggest the pathogenic
      role of anti-SRP and anti-HMGCR antibodies. SUMMARY: IMNM are muscle-specific
      autoimmune diseases associated with a severe weakness and a risk poor muscle
      strength recovery. Anti-SRP and anti-HMGCR antibodies are specifically associated
      with this condition and are crucial for the diagnosis and the prognosis. The
      muscle biopsy remains necessary for IMNM diagnosis in absence of myositis
      specific antibodies.

PMID- 30239350
TI  - Antisynthetase syndrome pathogenesis: knowledge and uncertainties.
AB  - PURPOSE OF REVIEW: Antisynthetase syndrome (ASyS) is an acquired myopathy
      characterized by the presence of myositis-specific autoantibodies directed
      against tRNA-synthetases. ASyS is potentially life threatening due to lung
      involvement and treatment remains a challenge to date. With symptoms not limited
      to muscles but also involving lung, skin and joints, ASyS appears specific and
      has a particular pathogenesis, different from the other inflammatory myopathies.
      This review is intended to discuss the current understanding of ASyS
      pathogenesis, pointing its current knowledge and also the crucial prospects that
      may lead to critical improvement of ASyS care. RECENT FINDINGS: Regarding ASyS
      pathogenesis, initiation of the disease seems to arise in a multifactorial
      context, with first lesions occurring within the lungs. This may lead to aberrant
      self-antigen exposure and tolerance breakdown. The consequences are abnormal
      activation of both innate and adaptive immunity, resulting in the patients with
      favourable genetic background to autoimmune-mediated organ lesions. Immune and
      nonimmune roles of the antigen, as well as antigen presentation leading to
      specific T-cell and B-cell activation and to the production of specific
      autoantibodies belong to the disease process. SUMMARY: This work aims to detail
      ASyS pathogenesis understanding, from initiation to the disease propagation and
      target tissue lesions, in order to considering future treatment directions.

PMID- 30239351
TI  - Genetics of perioperative pain management.
AB  - PURPOSE OF REVIEW: The current review will discuss the current literature on
      genetics of pain and analgesia, with special emphasis on perioperative setting.
      We will also discuss pharmacogenetics-based management guidelines, current
      clinical status and future perspectives. RECENT FINDINGS: Recent literature
      suggests that the interindividual variability in pain and postoperative analgesic
      response is at least in part because of one's genetic make-up. Some of the well
      characterized polymorphisms that are associated with surgical pain and opioid
      related postoperative adverse outcomes are described in catechol-O-methyl
      transferase, CYP2D6 and MU-opioid receptor (OPRM1), ATP-binding cassette
      subfamily B member 1, ABCC3, organic cation transporter 1 genes. Clinical
      Pharmacogenetics Implementation Consortium has put forth recommendations on
      CYP2D6 genotype-based opioid selection and dosing. The list of drug-gene pairs
      studied continue to expand. SUMMARY: Pharmacogenetic approach marks the dawn of
      personalized pain medicine both in perioperative and chronic pain settings.

PMID- 30239352
TI  - Intestinal cholesterol absorption.

PMID- 30239353
TI  - CORR Insights(r): Revisions of Modular Metal-on-metal THA Have a High Risk of
      Early Complications.

PMID- 30239354
TI  - Editorial: What is Narrative Medicine, and Why Should We Use it in Orthopaedic
      Practice?

PMID- 30239355
TI  - Ten Trials of a Cardiovascular Clinical Trialist.

PMID- 30239356
TI  - Reducing adverse medication events in mental health: Australian National Survey.
AB  - AIM: To determine the extent to which evidence-based medication safety practices
      have been implemented in public and private mental health inpatient units across
      Australia. METHODS: The Reducing Adverse Medication Events in Mental Health
      survey was piloted in Victoria, Australia, in 2015, and rolled out nationally in
      2016. In total, 235 mental health inpatient units from all States and Territories
      in Australia were invited to participate. The survey included questions about the
      demographics of the mental health unit, evidence-based strategies to improve
      prescription writing, the administration and dispensing of medicines and pharmacy
      led interventions, and also questions relating to consumer engagement in
      medication management and shared decision-making. RESULTS: The response rate was
      45% (N = 106 units). Overall, the survey found that 57% of the mental health
      units had fully or partially implemented evidence-based medication safety
      practices. High levels of implementation (80%) were reported for the use of
      standardized medication charts such as the National Inpatient Medication Chart as
      a way to improve medication prescription writing. Most (71%) of the units were
      using standardized forms for recording medication histories, and 56% were using
      designated forms for Medication Management Plans. However, less than one-fifth of
      the units had implemented electronic medication management systems, and the
      majority of units still relied on paper-based documentation systems.Interventions
      to improve medicine administration and dispensing were not highly utilized.
      Individual patient-based medication distribution systems were fully implemented
      in only 9% of the units, with a high reliance (81%) on ward stock or imprest
      systems. Tall Man lettering for labelling was implemented in only one-third of
      the units.Pharmacy services were well represented in mental health units, with
      80% having access to onsite pharmacist services providing assessments of current
      medications and clinical review services, adverse drug reaction reporting and
      management services, patient and carer education and counselling, and medicines
      information services. However, pharmacists were involved in only half of medical
      reconciliations. Their involvement in post-discharge follow-up was limited to 4%
      of units. CONCLUSIONS: Gaps in medication safety practices included limited use
      of individual patient supply systems for medication distribution, a high reliance
      on ward stock systems and high reliance on paper-based systems for medication
      prescribing and administration. With regards to service provision, clinical
      pharmacist involvement in medical reconciliation services, therapeutic drug
      monitoring and interdisciplinary ward rounds should be increased. Discharge and
      post-discharge services were major gaps in service provision.

PMID- 30239357
TI  - The development of software to support multiple systematic review types: the
      Joanna Briggs Institute System for the Unified Management, Assessment and Review
      of Information (JBI SUMARI).
AB  - AIM: Systematic reviews play an important role in ensuring trustworthy
      recommendations in healthcare. However, systematic reviews can be laborious to
      undertake and as such software has been developed to assist in the conduct and
      reporting of systematic reviews. The Joanna Briggs Institute and its
      collaborating centres consist of thousands of researchers, academics and
      clinicians across the globe conducting systematic reviews of various types. To
      support them in their work, modern software and online tools are required. Our
      aim was to develop a software program to support systematic reviewers across the
      globe. METHODS: A working party was formed with extensive consultation with
      members of the Joanna Briggs Collaboration focusing on ideal features of a
      software program to support systematic reviews. The new systematic review
      software was built using an agile methodology and designed to be a modern web
      application. RESULTS: The new systematic review software, the Joanna Briggs
      Institute System for the Unified Management, Assessment and Review of Information
      (JBI SUMARI), was successfully developed through an iterative process of
      development, feedback, testing and review. The software is now available
      (https://www.jbisumari.org/) and supports the entire systematic review process
      for different types of systematic reviews. CONCLUSIONS: An agile software
      development approach combined with wide consultation and user testing can
      facilitate systematic review software design and development. This new software
      can support systematic reviews and guideline developers to create systematic
      reviews for a diverse range of questions.

PMID- 30239358
TI  - Current and future tools for determination and monitoring of isocitrate
      dehydrogenase status in gliomas.
AB  - PURPOSE OF REVIEW: Hotspot mutations of isocitrate dehydrogenase 1 (R132) or 2
      (R172) genes affect 40% of diffuse gliomas, mostly grades II and III. The mutant
      enzyme produces high quantities of d-2-hydroxyglutarate (D2HG), which reshapes
      the epigenetic of the cell leading to gliomagenesis. For the clinician, the
      isocitrate dehydrogenase (IDH) mutation is a major biomarker with diagnostic,
      prognostic, and predictive consequences. With the development of specific
      inhibitors and vaccination, it appears also a potential actionable target. RECENT
      FINDINGS: IDH status is routinely determined on tumor sample by sequencing and
      immunohistochemistry detecting the most common mutant protein (IDH1R132H).
      Recently noninvasive diagnostic approaches have been developed based on the
      detection of the mutant DNA or the D2HG in body fluids, and the detection of D2HG
      by magnetic resonance spectroscopy of the brain. SUMMARY: These new techniques
      open avenues for non invasive diagnostic of glioma in patients not amenable to
      biopsy, in the preoperative setting and also duringpatients follow-up for
      evaluation of treatment response and prediction of recurrence.

PMID- 30239359
TI  - Role of amino-tracer PET for decision-making in neuro-oncology.
AB  - PURPOSE OF REVIEW: To give an overview on the current development in PET imaging
      as an additional tool in brain tumor management. RECENT FINDINGS: The rising
      emphasis on molecular tumor characteristics both in primary and in metastatic
      brain disease leads to an increased demand for noninvasive 'molecular' grading as
      well as treatment planning and surveillance of therapy effects. Metabolic imaging
      using amino acid PET provides further insights into tumor metabolism; current
      novelties comprise the use of hybrid PET/MRI scanners as well as development of
      new tracers. Furthermore, treatment monitoring and prognostication on the basis
      of amino acid PET is gaining further importance in neuro-oncological decision
      making. SUMMARY: Due to its unique properties in visualization of tumor biology,
      amino acid PET will continue to gain further importance in primary and secondary
      brain tumors.

PMID- 30239360
TI  - Stroke mimics and chameleons.
AB  - PURPOSE OF REVIEW: A stroke mimic is a situation in which a diagnosis of stroke
      at admission is not confirmed, and a stroke chameleon is a situation in which a
      stroke is revealed by clinical symptoms that are not usual in stroke. The
      objective of this review is to identify the most frequent clinical situations in
      which stroke mimics and chameleons are encountered and consequences for the
      patient. RECENT FINDINGS: The safety profile of intravenous thrombolysis (IVT) in
      patients who have stroke mimics is excellent, and intracranial hemorrhages are
      rare. Modern neuroimaging techniques help identifying most mimics. For stroke
      chameleons the role of imaging may be less important, especially when the
      clinical presentation is not suggestive of a brain disorder that request
      immediate neuroimaging. Education of health providers to identify such situations
      is crucial. SUMMARY: Stroke mimics account for up to 25% of admissions for
      probable strokes. The proportion of patients with stroke mimics decreases with
      use of MRI at baseline. Mimics cannot always be ruled out in emergency. The
      problem with mimics is that stroke facilities are not properly used, and patients
      may receive IVT. However, thrombolysis is usually well tolerated in mimics and we
      should not spend much time in all patients to improve diagnostic accuracy,
      knowing that the time lost is harmful in all patients, and will only prevent
      treating one mimic out of 100 patients. The problem with chameleons is more
      serious, because patients are not identified, and are not properly treated.

PMID- 30239361
TI  - Pediatric Papilledema: Review and a Clinical Care Algorithm.

PMID- 30239362
TI  - Disorders of the Pediatric Pupil.

PMID- 30239363
TI  - Pediatric Nystagmus.

PMID- 30239364
TI  - A Review of Optic Disc Drusen in Children.

PMID- 30239366
TI  - Optic Pathway Gliomas in Neurofibromatosis Type 1: Imaging and Monitoring.

PMID- 30239367
TI  - Pediatric Optic Neuritis and Other Demyelinating Optic Neuropathies.

PMID- 30239368
TI  - Pediatric Optic Disc Pallor.

PMID- 30239365
TI  - Effects of Brain Tumors on Vision in Children.

PMID- 30239369
TI  - Myelinated Retinal Nerve Fiber Layer (RNFL): A Comprehensive Review.

PMID- 30239370
TI  - In-Site Monocyte Implantation in Bone Grafting for Maxillary Atrophy
      Reconstruction: A Preliminary Observational Proof of Concept Study.
AB  - PURPOSE: The main objective of this study, involving 11 patients, is to share our
      experience on an integrated treatment modality, namely, the use of cellular
      therapy simultaneously with surgical reconstruction. Published works show that
      the implantation of monocytes in ischemic tissue enhances healing by providing
      neo-angiogenesis, a key mechanism in tissue regenerative processes. MATERIALS AND
      METHODS: Our approach included the utilization of autologous monocytes and
      endothelial precursor cells in the bone graft itself to improve the success rate
      of the integration of the bone graft and its long-term viability/survival by
      promoting angiogenesis. We compared the standard regenerative procedures, namely
      sinus lift grafting performed with xenogeneic particle bone graft and posterior
      mandible grafting performed with on-lay or in-lay autologous cortical/medullary
      bone-block graft harvested from the iliac crest, with and without the use of
      cellular implementation. We evaluated results by both radiological and
      histological assessment. RESULTS: Autologous cortical/medullary bone-block graft
      had a different response to implementation with monocytes, showing a better
      osteointegration than expected conversely to the xenogeneic particle bone graft.
      CONCLUSIONS: Monocytes seem to improve autologous bone-block graft according to
      the "Therapeutic Angiogenesis" concept. Implementation with monocytes does not
      always improve xenogeneic particle bone graft.

PMID- 30239371
TI  - Pediatric eosinophilic esophagitis: updates for the primary care setting.
AB  - PURPOSE OF REVIEW: Eosinophilic esophagitis (EoE) is a multifactorial, non-IgE
      mediated inflammatory disorder of the esophagus and is the most common cause of
      food impaction in the pediatric population. The purpose of this review is to
      describe the current recommendations for diagnosis and management of EoE. RECENT
      FINDINGS: New data has associated EoE with other allergic disorders of the atopic
      march as well as several risk factors, which predispose to allergic conditions. A
      subset of patients with esophageal eosinophilia respond to proton pump inhibitor
      (PPI) therapy with a partial or complete resolution of esophageal eosinophilia.
      Therefore, some patients can be treated with PPI alone. If this is unsuccessful,
      dietary elimination and swallowed steroid therapy are recommended for long-term
      management. There is a growing appreciation that untreated esophageal
      inflammation can lead to complications of fibrosis and stricture formation.
      SUMMARY: The current review will focus on the diagnosis and management of EoE in
      the pediatric population. Identification and diagnosis of pediatric patients with
      EoE is critical to prevent long-term esophageal complications.

PMID- 30239372
TI  - Pregnancy outcome in mothers over the age of 35.
AB  - PURPOSE OF REVIEW: The proportion of pregnancies occurring in women of at least
      35 years of age has increased from 6.2% in 1980 to 22.3% of births in 2016. This
      review summarizes recent epidemiological and basic scientific studies
      investigating the association between older maternal age and adverse pregnancy
      outcome(s), and clinical studies which investigate the effects of intervention to
      reduce adverse events. RECENT FINDINGS: Women of at least 35 years of age have
      increased risk of maternal and foetal complications in pregnancy including:
      stillbirth, a small for gestational age baby, preterm birth, preeclampsia and
      maternal death. These risks increase with increasing age. The reasons for this
      increased risk are incompletely understood, but likely involve ageing of the
      maternal cardiovascular and endocrine systems which impacts upon placental
      function. Intervention, by induction of labour (IOL) at 39-week gestation does
      not increase operative deliveries or short-term adverse maternal and neonatal
      outcomes and would reduce perinatal mortality. SUMMARY: The additional risks of
      pregnancy should be discussed with women of at least 35 years of age; additional
      foetal surveillance may be required in the antenatal period. The benefits and
      risks of IOL at 39-week gestation should be discussed with women at least 35
      years of age.

PMID- 30239373
TI  - Health outcomes associated with use of hormonal contraception: breast cancer.
AB  - PURPOSE OF REVIEW: To review recent literature on health outcomes associated with
      use of hormonal contraception with a focus on breast cancer. RECENT FINDINGS: A
      large cohort study documented an increased risk of breast cancer among hormonal
      contraceptive users compared to those who had never used hormonal contraception.
      The overall relative risk of breast cancer among current or recent users was 1.2
      [95% confidence interval (CI), 1.14-1.26]. Overall, this translates into one
      additional case of breast cancer for every 7690 users of hormonal contraception.
      Recent publications have also documented a decrease in risk for endometrial,
      ovarian, and colorectal cancers among hormonal contraceptive users. Based on
      these data, it is estimated that a third of endometrial and ovarian cancers and a
      fifth of colorectal cancers were prevented with combined oral contraceptive use.
      SUMMARY: Several factors must be taken into consideration regarding the risk of
      breast cancer associated with hormonal contraceptive use. Contraceptive benefits
      related to preventing unintended pregnancy are protective against associated
      maternal morbidity and mortality. Noncontraceptive benefits of protecting against
      other types of cancers must also be considered. Overall, breast cancer risk is
      low among hormonal contraceptive users and women should be counseled accordingly.

PMID- 30239374
TI  - The Relationship Between the Quality of Work and Organizational Commitment of
      Prison Nurses.
AB  - BACKGROUND: Nurses working in prisons are exposed to security problems while
      serving those who may be uninterested in their own healthcare, face high risks of
      drug and alcohol addiction, and may have aggressive personalities. For this
      reason, nurses working in prisons may have more problems with work-related
      quality of life than their non-prison-nurse peers. PURPOSE: This descriptive
      research study was conducted to evaluate the work-related quality of life and
      organizational commitment of nurses who work at prisons and detention centers.
      METHODS: According to 2015 data, approximately 513 nurses currently work in
      prisons in Turkey. The study group consisted of 224 nurses who currently work in
      prisons or detention centers. The data were collected by sending a created link
      address to the e-mail addresses of nurses who work in these facilities. A 13-item
      sociodemographic information form, including a demographics datasheet, a work
      related quality of life scale, and an organizational commitment scale, was used
      to collect data. RESULTS: The participants reported a moderate level of work
      related quality of life and organizational commitment. Moreover, work-related
      quality of life was shown to affect organizational commitment, with 20% of the
      total variance in organizational commitment explained by work-related quality of
      life. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study supports that work
      related quality of life affects organizational commitment positively. Therefore,
      regulating working conditions by taking into consideration employee security will
      positively affect job satisfaction in terms of both the institution and the
      employee. Moreover, as nurses do not only work in hospitals, taking this action
      should also work in different settings. Administrators should ensure the work
      related quality of life of the prison nurses by understanding the difficulties of
      prison nursing.

PMID- 30239375
TI  - Tranexamic Acid Administration is Associated With an Increased Risk of Post
      Traumatic Venous Thromboembolism.
AB  - BACKGROUND: Tranexamic acid (TXA) is used as a hemostatic adjunct for hemorrhage
      control in the injured patient and reduces early preventable death. But the risk
      of venous thromboembolism (VTE) has been incompletely explored. Previous studies
      investigating the effect of TXA on VTE vary in their findings. We performed a
      propensity matched analysis to investigate the association between TXA and VTE
      following trauma, hypothesizing that TXA is an independent risk factor for VTE.
      METHODS: This retrospective study queried trauma patients presenting to a single
      level I trauma center from 2012 to 2016. Our primary outcome was composite
      pulmonary embolism or deep vein thrombosis. Mortality, transfusion, ICU and
      hospital lengths of stay (LOS) were secondary outcomes. Propensity matched mixed
      effects multivariate logistic regression was used to determine adjusted odds
      ratio (aOR) and 95% confidence intervals of TXA on outcomes of interest,
      adjusting for prespecified confounders. Competing risks regression assessed
      subdistribution hazard ratio (SHR) of VTE after accounting for mortality.
      RESULTS: Out of 21,931 patients, 189 pairs were well matched across propensity
      score variables (standardized differences <0.2). Median ISS was 19 (IQR 12, 27)
      and 14 (IQR 8, 22) in TXA and non-TXA groups, respectively (p=0.19). TXA was
      associated with more than 3-fold increase in the odds of VTE (aOR 3.3; 95%CI 1.3
      9.1, p=0.02). TXA was not significantly associated with survival (aOR 0.86; 95%CI
      0.23-3.25, p=0.83). Risk of VTE remained elevated in the TXA cohort despite
      accounting for mortality (SHR 2.42; 95% CI 1.11-5.29, p=0.03). CONCLUSION: TXA
      may be an independent risk factor for VTE. Future investigation is needed to
      identify which patients benefit most from TXA, especially given risks of this
      intervention, to allow a more individualized treatment approach that maximizes
      benefits and mitigates potential harms. LEVEL OF EVIDENCE: Level III;
      Therapeutic.

PMID- 30239376
TI  - The ROMA trial: why it is needed.
AB  - PURPOSE OF REVIEW: We herein summarize the current evidence on the clinical
      outcome associated with the use of single and multiple arterial grafts for
      coronary bypass surgery and the role and importance of the Randomized comparison
      of the clinical Outcome of single versus Multiple Arterial grafts (ROMA) trial.
      RECENT FINDINGS: Observational evidence suggests that the use of multiple
      arterial grafts is associated with better clinical outcomes compared to the use
      of a single arterial graft. Randomized evidence is inconclusive; the 5-year
      interim analysis of the largest randomized trial on the topic did not show any
      clinical benefit associated with the use of bilateral versus single internal
      thoracic arteries, whereas a pooled analysis of the trials comparing the radial
      artery and the saphenous vein as a second graft showed a significant reduction in
      follow-up cardiac events using the radial artery. Hidden confounders and
      treatment allocation biases as well as methodological flaws are the most likely
      explanation of this contradiction. SUMMARY: ROMA was conceived based on the
      lessons learned from a critical analysis of the existing randomized and
      observational evidence with the aim to provide a definitive answer to the
      question of the potential clinical benefit of multiple arterial grafts for
      coronary bypass.

PMID- 30239377
TI  - The clinical impact of glucose-6-phosphate dehydrogenase deficiency in patients
      with sickle cell disease.
AB  - PURPOSE OF REVIEW: Glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle
      cell disease (SCD) cause hemolysis, often occurring in individuals of African
      descent. These disorders co-occur frequently, and possibly interact, altering
      clinical outcomes in SCD. However, epidemiological investigations of SCD with
      G6PD deficiency have produced variable results. This contribution reviews the
      available data about the interaction of G6PD deficiency and SCD. RECENT FINDINGS:
      Overall, G6PD deficiency contributes few, if any, effects to laboratory values
      and clinical outcomes in SCD patients, but may impact transfusion efficacy. This
      observation is most likely because of the relatively increased G6PD activity in
      the young red blood cell (RBC) population seen in SCD patients with or without
      G6PD deficiency. In addition, G6PD deficiency possibly interacts with other
      genetic modifiers, such as alpha thalassemia, hemoglobin F levels and SCD
      haplotype. SUMMARY: Although G6PD deficiency is relatively common, it does not
      appear to clinically impact patients with SCD. Nonetheless, it is important to
      evaluate G6PD status in patients with SCD to avoid the use of medications that
      may cause hemolysis. Future studies evaluating the clinical impact of
      transfusions from G6PD-deficient RBC donors would be of the greatest benefit to
      the current literature.

PMID- 30239378
TI  - Current and future status of stem cell expansion.
AB  - PURPOSE OF REVIEW: Herein, we seek to describe the current and future role of ex
      vivo expansion of cord blood hematopoietic stem cells. RECENT FINDINGS: As this
      field is only in its infancy, there have been many challenges identified.
      Decreased number of stem cells contained in a cord blood unit and early
      differentiation of stem cells once expanded have been two overarching challenges
      faced by the field. Many recent techniques have focused on the properties of the
      microenvironment and targetable cellular pathways as novel approaches to
      circumvent these challenges. SUMMARY: Novel discoveries have led to the
      development of approaches that will increase hematopoietic stem cell yield and
      will improve engraftment in patients receiving cord blood hematopoietic stem cell
      transplantation. As a result, patients receiving cord blood hematopoietic stem
      cell transplantationcontinue to have improved outcomes.

PMID- 30239379
TI  - Obstructive sleep apnea and chronic kidney disease.
AB  - PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is highly prevalent in patients
      with chronic kidney disease (CKD). The relationship between OSA and CKD is likely
      to be bi-directional. On one hand, the presence of OSA leads to intermittent
      hypoxia, sympathetic nervous system activity, and hypertension, all of which may
      have deleterious effects on kidney function. On the other hand, in patients with
      end-stage renal disease (ESRD), intensification of renal replacement therapy has
      been shown to attenuate sleep apnea severity, suggesting that the renal disease
      itself contributes to the pathogenesis of OSA. The present review describes our
      current understanding of the bi-directional relationship between OSA and CKD.
      RECENT FINDINGS: Studies suggest that the presence of OSA and nocturnal hypoxia
      may lead to worsening of kidney function. One potential mechanism is activation
      of the renin-angiotensin system by OSA, an effect which may be attenuated by CPAP
      therapy. In ESRD, fluid overload plays an important role in the pathogenesis of
      OSA and fluid removal by ultrafiltration leads to marked improvements in sleep
      apnea severity. SUMMARY: OSA is associated with accelerated loss of kidney
      function. In patients with ESRD, fluid overload plays an important role in the
      pathogenesis of OSA.

PMID- 30239380
TI  - Updates in vitamin D therapy in cystic fibrosis.
AB  - PURPOSE OF REVIEW: To summarize recent developments the role of vitamin D and
      treatment of vitamin D deficiency in cystic fibrosis. RECENT FINDINGS: Although
      treatment of low vitamin D levels continues to be important for optimizing bone
      health in cystic fibrosis, increasing data on the extraskeletal effects of
      vitamin D are becoming available. Exploratory studies of vitamin D in modulation
      of respiratory and intestinal microbiomes, and the influence of vitamin D on the
      metabolomic signature of cystic fibrosis, suggest expanded roles for vitamin D in
      cystic fibrosis disease and treatment. SUMMARY: Emerging developments in cystic
      fibrosis regarding therapeutics and effects of vitamin D on bone health,
      inflammation, microbiome, and the metabolome are summarized.

PMID- 30239381
TI  - Extracorporeal CO2 Removal: The Minimally Invasive Approach, Theory, and
      Practice.
AB  - OBJECTIVES: Minimally invasive extracorporeal CO2 removal is an accepted
      supportive treatment in chronic obstructive pulmonary disease patients.
      Conversely, the potential of such technique in treating acute respiratory
      distress syndrome patients remains to be investigated. The aim of this study was:
      1) to quantify membrane lung CO2 removal (VCO2ML) under different conditions and
      2) to quantify the natural lung CO2 removal (VCO2NL) and to what extent
      mechanical ventilation can be reduced while maintaining total expired CO2
      (VCO2tot = VCO2ML + VCO2NL) and arterial PCO2 constant. DESIGN: Experimental
      animal study. SETTING: Department of Experimental Animal Medicine, University of
      Gottingen, Germany. SUBJECTS: Eight healthy pigs (57.7 +/- 5 kg). INTERVENTIONS:
      The animals were sedated, ventilated, and connected to the artificial lung system
      (surface 1.8 m, polymethylpentene membrane, filling volume 125 mL) through a 13F
      catheter. VCO2ML was measured under different combinations of inflow PCO2 (38.9
      +/- 3.3, 65 +/- 5.7, and 89.9 +/- 12.9 mm Hg), extracorporeal blood flow (100,
      200, 300, and 400 mL/min), and gas flow (4, 6, and 12 L/min). At each setting, we
      measured VCO2ML, VCO2NL, lung mechanics, and blood gases. MEASUREMENTS AND MAIN
      RESULTS: VCO2ML increased linearly with extracorporeal blood flow and inflow PCO2
      but was not affected by gas flow. The outflow PCO2 was similar regardless of
      inflow PCO2 and extracorporeal blood flow, suggesting that VCO2ML was maximally
      exploited in each experimental condition. Mechanical ventilation could be reduced
      by up to 80-90% while maintaining a constant PaCO2. CONCLUSIONS: Minimally
      invasive extracorporeal CO2 removal removes a relevant amount of CO2 thus
      allowing mechanical ventilation to be significantly reduced depending on
      extracorporeal blood flow and inflow PCO2. Extracorporeal CO2 removal may provide
      the physiologic prerequisites for controlling ventilator-induced lung injury.

PMID- 30239382
TI  - Renal Klotho is Reduced in Septic Patients and Pretreatment With Recombinant
      Klotho Attenuates Organ Injury in Lipopolysaccharide-Challenged Mice.
AB  - OBJECTIVES: To determine the applicability of recombinant Klotho to prevent
      inflammation and organ injury in sepsis in man and mice. DESIGN: Prospective,
      clinical laboratory study using "warm" human postmortem sepsis-acute kidney
      injury biopsies. Laboratory study using a mouse model of endotoxemia. SETTING:
      Research laboratory at a university teaching hospital. SUBJECTS: Adult patients
      who died of sepsis in the ICU and control patients undergoing total nephrectomy
      secondary to renal cancer; male C57BL/6 and Klotho haploinsufficient mice.
      INTERVENTIONS: Lipopolysaccharide (0.05 mg/kg) injection and kill after 4, 8, and
      24 hours. Mice received recombinant Klotho (0.05 mg/kg) 30 minutes prior to
      lipopolysaccharide (1 mg/kg) injection. Mice treated with saline were included as
      controls. MEASUREMENTS AND MAIN RESULTS: Quantitative reverse transcription
      polymerase chain reaction and immunohistochemical staining were used to quantify
      Klotho messenger RNA and protein expression in the kidney of sepsis-acute kidney
      injury patients and the kidney and brain of mice. The messenger RNA and protein
      expression of damage markers, inflammatory cytokine, chemokines, and endothelial
      adhesion molecules were also determined in mice. Renal neutrophil influx was
      quantified. We found significantly lower renal Klotho messenger RNA and protein
      levels in sepsis-acute kidney injury biopsies than in control subjects. These
      findings were recapitulated in the kidney and brain of lipopolysaccharide
      challenged mice. Decreased Klotho expression paralleled an increase in kidney
      damage markers neutrophil gelatinase-associated lipocalin and kidney injury
      molecule-1. Administration of recombinant Klotho prior to lipopolysaccharide
      injection attenuated organ damage, inflammation and endothelial activation in the
      kidney and brain of mice. Furthermore, less neutrophils infiltrated into the
      kidneys of recombinant Klotho mice compared with lipopolysaccharide only treated
      mice. CONCLUSIONS: Renal Klotho expression in human sepsis-acute kidney injury
      and in mouse models of sepsis was significantly decreased and correlated with
      renal damage. Recombinant Klotho intervention diminished organ damage,
      inflammation, and endothelial activation in the kidney and brain of
      lipopolysaccharide-challenged mice. Systemic Klotho replacement may potentially
      be an organ-protective therapy for septic patients to halt acute, inflammatory
      organ injury.

PMID- 30239383
TI  - Meaning of Intracranial Pressure-to-Blood Pressure Fisher-Transformed Pearson
      Correlation-Derived Optimal Cerebral Perfusion Pressure: Testing Empiric Utility
      in a Mechanistic Model.
AB  - OBJECTIVES: Time-averaged intracranial pressure-to-blood pressure Fisher
      transformed Pearson correlation (PRx) is used to assess cerebral autoregulation
      and derive optimal cerebral perfusion pressure. Empirically, impaired cerebral
      autoregulation is considered present when PRx is positive; greater difference
      between time series median cerebral perfusion pressure and optimal cerebral
      perfusion pressure (DeltaCPP) is associated with worse outcomes. Our aims are to
      better understand: 1) the potential strategies for targeting optimal cerebral
      perfusion pressure; 2) the relationship between cerebral autoregulation and PRx;
      and 3) the determinants of greater DeltaCPP. DESIGN: Mechanistic simulation using
      a lumped compartmental model of blood pressure, intracranial pressure, cerebral
      autoregulation, cerebral blood volume, PaCO2, and cerebral blood flow. SETTING:
      University critical care integrative modeling and precision physiology research
      group. SUBJECTS: None, in silico studies. INTERVENTIONS: Simulations in blood
      pressure, intracranial pressure, PaCO2, and impairment of cerebral
      autoregulation, with examination of "output" cerebral perfusion pressure versus
      PRx-plots, optimal cerebral perfusion pressure, and DeltaCPP. MEASUREMENTS AND
      MAIN RESULTS: In regard to targeting optimal cerebral perfusion pressure, a shift
      in mean blood pressure or mean intracranial pressure with no change in mean blood
      pressure, with intact cerebral autoregulation, impacts optimal cerebral perfusion
      pressure. Second, a positive PRx occurs even with intact cerebral autoregulation.
      In relation to DeltaCPP, for a given input blood pressure profile, with constant
      intracranial pressure, altering the degree of impairment in cerebral
      autoregulation or the level of PaCO2 maintains differences to within +/-5 mm Hg.
      Change in intracranial pressure due to either an intermittently prolonged pattern
      of raised intracranial pressure or terminal escalation shows DeltaCPP greater
      than 10 mm Hg and less than -10 mm Hg, respectively. CONCLUSIONS: These
      mechanistic simulations provide insight into the empiric basis of optimal
      cerebral perfusion pressure and the significance of PRx and DeltaCPP. PRx and
      optimal cerebral perfusion pressure deviations do not directly reflect changes in
      cerebral autoregulation but are, in general, related to the presence of complex
      states involving well-described clinical progressions with raised intracranial
      pressure.

PMID- 30239384
TI  - Benzodiazepines for agitation in patients with delirium: selecting the right
      patient, right time, and right indication.
AB  - PURPOSE OF REVIEW: To provide an evidence-based synopsis on the role of
      benzodiazepines in patients with agitated delirium. RECENT FINDINGS: Existing
      evidence supports the use of benzodiazepines in two specific delirium settings:
      persistent agitation in patients with terminal delirium and delirium tremens. In
      the setting of terminal delirium, the goal of care is to maximize comfort,
      recognizing that patients are unlikely to recover from their delirium. A recent
      randomized trial suggests that lorazepam in combination with haloperidol as
      rescue medication was more effective than haloperidol alone for the management of
      persistent restlessness/agitation in patients with terminal delirium. In patients
      with refractory agitation, benzodiazepines may be administered as scheduled doses
      or continuous infusion for palliative sedation. Benzodiazepines also have an
      established role in management of delirium secondary to alcohol withdrawal.
      Outside of these two care settings, the role of benzodiazepine remains
      investigational and clinicians should exercise great caution because of the risks
      of precipitating or worsening delirium and over-sedation. SUMMARY:
      Benzodiazepines are powerful medications associated with considerable risks and
      benefits. Clinicians may prescribe benzodiazepines skillfully by selecting the
      right medication at the right dose for the right indication to the right patient
      at the right time.

PMID- 30239386
TI  - Palliative care for all? How can Brazil develop a palliative care service founded
      on principles of equity and access for all?
AB  - PURPOSE OF REVIEW: Despite the historical international development of palliative
      care over the last 50 years, provision of equity of care and access to
      appropriate medication remains a major problem in many countries across the
      world. Interest in the public health approach to end-of-life care has grown over
      the last 20 years. Models of palliative care, which are affordable and provide
      equity of care are changing through these new concepts. We describe an existing
      model of practice in a primary care setting in Rio Grande in Brazil, which could
      act as a template for redesign of palliative care services. RECENT FINDINGS:
      Traditional models of palliative care have focussed on the physical, social,
      psychological and spiritual domains. Abel and Kellehear have proposed a new
      model, uniting specialist and generalist palliative care with compassionate
      communities and the civic component encapsulated in the compassionate city
      charter. This model is more comprehensive, emphasizing both harm reduction and
      health and well being promotion, and is currently being rolled out within the
      Family Health Strategy in Rio Grande in Brazil. SUMMARY: An existing model of
      palliative care, which includes the public health approach in Rio Grande be used
      as a basis for more equitable palliative care in Brazil, to meet a large unmet
      need.

PMID- 30239385
TI  - What's next in using CT scans to better understand cachexia?
AB  - PURPOSE OF REVIEW: Cachexia (CAX), a protein metabolism disorder commonly
      associated with cancer, can be evaluated by computed tomography (CT) scan
      assessment of skeletal muscle mass (SMM), a parameter associated with patient
      outcome. This review analyzes current barriers for using CT scans of SMM in
      routine management for defining prognostic risk groups, and proposes new areas of
      research to reach a better understanding of CAX mechanisms. RECENT FINDINGS:
      Current research is focused on establishing a robust and relevant CAX staging
      system to reach a consensual definition. Previous biomarkers of CAX are poorly
      associated with outcome and do not exhibit clinical benefit. Systemic
      inflammatory marker, decrease in intake assessments, and/or nonnutritional
      criteria have been integrated to develop a multidimensional, highly complex CAX
      signature and CAX staging. SUMMARY: A standardized definition of sarcopenia is
      essential, and its value in clinical practice should be evaluated in prospective
      interventional studies using skeletal muscle assessment. SMM loss may be a key
      element in defining early protein disorders occurring before weight loss and
      could be used as a trigger for initiating early nutritional support. Changes in
      SMM and body composition during follow-up are useful tools for exploring CAX
      mechanisms in terms of intrinsic factors or tumor evolution.

PMID- 30239387
TI  - How should we assess patient-reported outcomes in the onco-hematology clinic?
AB  - PURPOSE OF REVIEW: The improvement of clinical outcomes in hematologic
      malignancies has paved the way for a more systematic patient-reported outcomes
      (PROs) assessment in routine clinical practice. PROs help to narrow the gap
      between patients' and healthcare professionals' view of patient health and
      treatment success. This review outlines key aspects of planning and performing
      PRO assessments in daily routine such as the selection of PRO instruments,
      electronic PRO data collection, and the presentation and interpretation of PRO
      results. RECENT FINDINGS: A substantial body of literature has demonstrated that
      careful planning, adequate logistics, and elaborate methodology allow to
      successfully integrate the patients' experience in routine care. Several examples
      exist of the clinical benefits of systematically collecting PRO information in
      daily care of patients with solid tumors. These include improved patient
      physician communication, better symptom management, and, in patients with
      advanced disease, also fewer hospitalizations and prolonged survival. However,
      sparse evidence based data are available for patients with onco-hematologic
      diseases. SUMMARY: Data collected through PRO instruments provide unique
      information that complements traditional clinical examinations and may help
      improving patients' management in clinical practice. Major efforts are now needed
      to implement PRO instruments in daily practice of patients with hematologic
      malignancies.

PMID- 30239388
TI  - We all need support but can our patients help us to help them?

PMID- 30239390
TI  - Perineal Stapled Rectal Prolapse Resection in Elderly Patients: Long-term Follow
      up.
AB  - BACKGROUND: Full-thickness rectal prolapse has a significant negative impact on
      quality of life. The therapeutic options, specifically in elderly patients, are
      imperfect. Perineal stapled rectal prolapse resection is a novel operation for
      treating external rectal prolapse. Long-term follow-up following this procedure
      is lacking. In our study, we report a long-term follow-up of 30 patients,
      analyzing the long-term recurrence rate, morbidity, and functional outcome.
      OBJECTIVE: This study aimed to examine the long-term results of perineal stapled
      rectal resection in a population unfit for prolonged general anesthesia. DESIGN:
      This was a cohort study with a prospective follow-up. SETTINGS: This study was
      conducted at a single tertiary referral center. PATIENTS: Patients undergoing
      perineal stapled rectal resection from January 2010 to June 2013 were included.
      INTERVENTIONS: Perineal stapled rectal prolapse resection was performed. MAIN
      OUTCOME MEASURES: The primary outcome measured was prolapse recurrence. RESULTS:
      A total of 30 patients underwent the surgical intervention. The median follow-up
      period was 61 months (range, 37-65). No intraoperative or postoperative
      complications occurred. Six patients (20%) had recurrent rectal prolapse, and
      continence was not achieved in any of the patients. Two patients who had
      recurrence underwent a redo perineal stapled rectal resection. LIMITATIONS: This
      study was limited by the small cohort of selected patients. CONCLUSIONS: Frail
      patients that can only endure a short procedure under regional anesthesia should
      be considered for perineal stapled rectal prolapse resection. The lack of
      mortality and morbidity, specifically in this population, along with the low long
      term recurrence rates, make this a favorable surgical alternative. See Video
      Abstract at http://links.lww.com/DCR/A745.

PMID- 30239389
TI  - PICU Autopsies: Rates, Patient Characteristics, and the Role of the Medical
      Examiner.
AB  - OBJECTIVES: Autopsy rates in North American Children's hospitals have not been
      recently evaluated. Our objectives were 1) to determine the autopsy rates from
      patients cared for in PICUs during a portion of their hospital stay, 2) to
      identify patient characteristics associated with autopsies, and 3) to understand
      the relative role of medical examiner cases. DESIGN: Secondary analysis of data
      prospectively collected from a sample of patients (n = 10,078) admitted to PICUs
      affiliated with the Collaborative Pediatric Critical Care Research Network
      between December 2011 and April 2013. SETTING: Eight quaternary care PICUs.
      PATIENTS: Patients in the primary study were less than 18 years old, admitted to
      a PICU and not moribund on PICU admission. Patients included in this analysis
      were those who died during their hospital stay. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Sociodemographic, clinical, hospital, and PICU data were
      compared between patients who had autopsies conducted and those who did not and
      between medical examiner and nonmedical examiner autopsies. Of 10,078 patients,
      275 died of which 36% (n = 100) had an autopsy performed. Patients with cancer
      who died were less likely to receive autopsies (p = 0.005), whereas those who
      died after trauma or cardiac arrest had autopsies performed more often (p <
      0.01). Autopsies were more common in patients with greater physiologic
      instability at admission (p < 0.001), and those who received more aggressive PICU
      care. Medical examiner cases comprised nearly half of all autopsies (n = 47; 47%)
      were conducted in patients presenting with greater physiologic instability (p <
      0.001) and more commonly after catastrophic events such as cardiac arrest or
      trauma (p < 0.001). CONCLUSIONS: In this first multicenter analysis of autopsy
      rates in children, 36% of deaths had autopsies conducted, of which nearly half
      were conducted by the medical examiner. Deaths with autopsy are more likely to be
      previously healthy children that had catastrophic events prior to admission.

PMID- 30239391
TI  - Readmissions With Dehydration After Ileostomy Creation: Rethinking Risk Factors.
AB  - BACKGROUND: Twenty-nine percent of postileostomy discharges are readmitted, most
      commonly because of dehydration. However, there is a lack of detailed data
      specifically evaluating factors associated with readmission with dehydration. In
      addition, patients with a history of an ileostomy have often been excluded from
      previous studies and therefore represent a group of understudied ileostomates.
      OBJECTIVE: This study aimed to evaluate factors available at discharge associated
      with 30-day readmission for dehydration, rather than all-cause readmissions.
      DESIGN: This was a retrospective cohort study. SETTING: Study patients received
      ileostomies at a tertiary academic medical center from 2014 to 2016. PATIENTS:
      Patients with a preexisting ileostomy that was not recreated per the operative
      note were excluded, whereas those who received a new ileostomy were included.
      MAIN OUTCOME MEASURE: The primary outcome measured was 30-day readmission for
      dehydration as defined by objective clinical criteria. RESULTS: A total of 262
      patients underwent ileostomy creation and were discharged alive. Twenty-five
      percent were >=65 years of age, 53% were men, 14% had a history of ileostomy, 18%
      had a creatinine >1.0 on discharge, and 26% had high ileostomy output at any time
      during the index admission. Among all ileostomates, the all-cause readmission
      rate was 30%. Mean days to readmission for any cause was 8.5, whereas for
      dehydration it was 11.6 days. Of the readmissions, 37% were readmitted with a
      diagnosis of dehydration, and dehydration was the sole reason in 26%. Among those
      with dehydration, the most common length of stay was 2 days. In multivariable
      logistic regression, 30-day readmission with dehydration was associated with
      older age, male sex, history of an ileostomy, high ileostomy output during index
      admission, and a discharge creatinine >1.0. LIMITATIONS: This study was limited
      by its retrospective design. CONCLUSIONS: Ileostomy dehydration efforts have
      focused on new ileostomy patients; however, our data suggest that patients with a
      history of an ileostomy are actually at risk for readmission with dehydration.
      Further studies aimed at the reduction of readmission with dehydration after
      ileostomy are warranted and should include patients with a history of an
      ileostomy. See Video Abstract at http://links.lww.com/DCR/A643.

PMID- 30239392
TI  - MiR-486-5p Downregulation Marks an Early Event in Colorectal Carcinogenesis.
AB  - BACKGROUND: MicroRNAs are dysregulated in colorectal cancer and subsets
      correlated with advanced tumor stage and metastasis. Data are lacking on microRNA
      dysregulation from early to late-stage disease. OBJECTIVE: The purpose of this
      study was to identify a microRNA signature associated with the primary tumor and
      metastatic site in stage IV disease and to examine whether the signature is
      evident in earlier stages. DESIGN: A microRNA profile was generated and then
      explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10),
      and late-stage (stage III and IV; n = 14) colorectal primary tumors via
      polymerase chain reaction to delineate molecular events that may promote
      colorectal carcinogenesis. SETTING: Genome-wide microRNA expression profiling was
      performed. PATIENTS: A total of 14 patient-matched stage IV primary colorectal
      cancer tumors and corresponding liver metastases were included. MAIN OUTCOME
      MEASURES: MicroRNA array technology was used to identify microRNA expression
      predictive metastatic potential in the primary tumor. RESULTS: A distinct 9
      member signature group of microRNAs was concurrent in stage IV primary colorectal
      cancer and their corresponding liver metastases, when compared with surrounding
      unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182,
      microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and
      microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially
      expressed in early stage colorectal cancer samples compared with normal tissue (p
      = 0.001) and additionally differentially expressed between late-stage colorectal
      cancer samples and normal tissue (p < 0.01). LIMITATIONS: Our microRNA profile
      was generated in a small subset of patients and will require validation in more
      samples. CONCLUSIONS: We identified a distinct microRNA signature in primary
      colon and matched metastatic disease. On additional investigation, 1 microRNA was
      differentially expressed in both early and late-stage cancer patient samples, and
      it may herald an early event in colorectal carcinogenesis. This study warrants
      additional investigation with a larger patient cohort to better understand the
      effect of microRNAs in carcinogenesis. See Video Abstract at
      http://links.lww.com/DCR/A723.

PMID- 30239393
TI  - Prognostic Impact of Hypochloremia in Patients With Stage I to III Colorectal
      Cancer After Radical Resection.
AB  - BACKGROUND: Recent studies have suggested that electrolyte disorders might be a
      negative prognostic factor for some diseases. OBJECTIVE: The purpose of this
      study was to systematically evaluate the prognostic role of electrolyte disorders
      in patients with stage I to III colorectal cancer who received radical surgical
      resection. DESIGN: This study was retrospectively performed. SETTINGS: The study
      was conducted at a single tertiary care center. PATIENTS: Patients with
      colorectal cancer who underwent radical resection in between April 2007 and April
      2014 were included. MAIN OUTCOME MEASURES: The Kaplan-Meier method was adopted to
      estimate the overall and disease-free survival with and without propensity score
      matching. RESULTS: In total, our study recruited 5089 eligible patients. In
      prematching analysis, patients with hypochloremia showed both shorter overall
      survival (HR = 0.943 (95% CI, 0.908-0.980); p = 0.003) and disease-free survival
      (HR = 0.957 (95% CI, 0.933-0.981); p < 0.001) than those with normal serum
      chloride levels. In postmatching analysis, 770 patients from each group were
      compared, and the results further confirmed that hypochloremia was significantly
      associated with worse overall survival (HR = 0.646 (95% CI, 0.489-0.855); p =
      0.002) and disease-free survival (HR = 0.782 (95% CI, 0.647-0.944); p = 0.01),
      with the hypochloremia group as a reference. LIMITATIONS: The study was limited
      by its retrospective nature. CONCLUSIONS: Hypochloremia diagnosed before
      treatment can independently prognosticate the overall and disease-free survival
      for patients with stage I to SH colorectal cancer after radical resection.
      Intensive surveillance and management might improve the survival outcome for
      patients with hypochloremia. See Video Abstract at http://links.lww.com/DCR/A727.

PMID- 30239394
TI  - Secondary Breast, Ovarian, and Uterine Cancers After Colorectal Cancer: A
      Nationwide Population-Based Cohort Study in Korea.
AB  - BACKGROUND: The risk of a second primary cancer has increased along with the
      increasing life expectancies of colorectal cancer survivors. OBJECTIVE: We aimed
      to evaluate the incidence rate and risk factors of breast and gynecological
      (ovarian, uterine cervix/corpus) cancers among female colorectal cancer
      survivors. DESIGN: This is a retrospective population-based cohort study.
      SETTINGS: This study used data from the National Health Insurance Corporation of
      Korea. PATIENTS: Each patient with colorectal cancer diagnosed from 2007 to 2012
      was followed until 2015 and compared with age-matched women without colorectal
      cancer at a 1:5 ratio. MAIN OUTCOME MEASURES: The primary outcome was de novo
      breast/gynecological cancer. Patients with available medical checkup data were
      included in an additional analysis. RESULTS: We analyzed 56,682 patients with
      colorectal cancer and 288,119 age-matched noncolorectal cancer controls. The risk
      of breast/gynecological cancer was higher among patients with colorectal cancer
      than among controls (HR, 2.91; p < 0.001). The association with colorectal cancer
      was the highest for ovarian cancer (HR, 6.72), followed by uterine corpus cancer
      (HR, 3.99), cervical cancer (HR, 2.82), and breast cancer (HR, 1.85). This
      association remained consistent in the subgroup analysis of medical checkup data
      (14,190 patients with colorectal cancer, 71,933 controls). Among patients with
      colorectal cancer, those aged <55 years had a higher risk of breast/gynecological
      cancers than those aged >55 years (HR, 3.51 vs 2.59), and those with dyslipidemia
      had a higher risk of breast cancer than those without dyslipidemia (HR, 2.66 vs
      2.06). LIMITATIONS: This was a retrospective, population-based study. A
      prospectively designed study is needed to validate our conclusions. CONCLUSIONS:
      Compared with the general population, patients with colorectal cancer carry a
      higher risk of developing secondary breast, ovarian, and uterine cancers. See
      Video Abstract at http://links.lww.com/DCR/A731.

PMID- 30239395
TI  - Different Risk Factors for Early and Late Colorectal Anastomotic Leakage in a
      Nationwide Audit.
AB  - BACKGROUND: Anastomotic leakage remains a major complication after surgery for
      colorectal carcinoma, but its origin is still unknown. Our hypothesis was that
      early anastomotic leakage is mostly related to technical failure of the
      anastomosis, and that late anastomotic leakage is mostly related to healing
      deficiencies. OBJECTIVE: The aim of this study was to assess differences in risk
      factors for early and late anastomotic leakage. DESIGN: This was a retrospective
      cohort study. SETTINGS: The Dutch ColoRectal Audit is a nationwide project that
      collects information on all Dutch patients undergoing surgery for colorectal
      cancer. PATIENTS: All patients undergoing surgical resection for colorectal
      cancer in the Netherlands between 2011 and 2015 were included. MAIN OUTCOME
      MEASURES: Late anastomotic leakage was defined as anastomotic leakage leading to
      reintervention later than 6 days postoperatively. RESULTS: In total, 36,929
      patients were included; early anastomotic leakage occurred in 863 (2.3%)
      patients, and late anastomotic leakage occurred in 674 (1.8%) patients. From a
      multivariable multinomial logistic regression model, independent predictors of
      early anastomotic leakage relative to no anastomotic leakage and late anastomotic
      leakage relative to no anastomotic leakage included male sex (OR, 1.8; p < 0.001
      and OR, 1.2; p = 0.013) and rectal cancer (OR, 2.1; p < 0.001 and OR, 1.6; p =
      0.046). Additional independent predictors of early anastomotic leakage relative
      to no anastomotic leakage included BMI (OR, 1.1; p = 0.001), laparoscopy (OR,
      1.2; p = 0.019), emergency surgery (OR, 1.8; p < 0.001), and no diverting
      ileostomy (OR, 0.3; p < 0.001). Independent predictors of late anastomotic
      leakage relative to no anastomotic leakage were Charlson Comorbidity Index of
      >=II (OR, 1.3; p = 0.003), ASA score III to V (OR, 1.2; p = 0.030), preoperative
      tumor complications (OR, 1.1; p = 0.048), extensive additional resection because
      of tumor growth (OR, 1.7; p = 0.003), and preoperative radiation (OR, 2.0; p =
      0.010). LIMITATIONS: This was an observational cohort study. CONCLUSIONS: Most
      risk factors for early anastomotic leakage were surgery-related factors,
      representing surgical difficulty, which might lead to technical failure of the
      anastomosis. Most risk factors for late anastomotic leakage were patient-related
      factors, representing the frailty of patients and tissues, which might imply
      healing deficiencies. See Video Abstract at http://links.lww.com/DCR/A730.

PMID- 30239396
TI  - Complications Arising From Perioperative Anticoagulant/Antiplatelet Therapy in
      Major Colorectal and Abdominal Wall Surgery.
AB  - BACKGROUND: Postoperative hemorrhage and thromboembolism are recognized
      complications following colorectal and abdominal wall surgery, but accurate
      documentation of their incidence, trends, and outcomes is scant. This is relevant
      given the increasing number of surgical patients with cardiovascular comorbidity
      on anticoagulant/antiplatelet therapy. OBJECTIVE: This study aims to characterize
      trends in the use of anticoagulant/antiplatelet therapy among patients undergoing
      major colorectal and abdominal wall surgery within the past decade, and to assess
      rates of, outcomes following, and risk factors for hemorrhagic and thromboembolic
      complications. DESIGN AND SETTING: This is a retrospective cross-sectional study
      conducted at a single quaternary referral center. PATIENTS: Patients who
      underwent major colorectal and abdominal wall surgery during three 12-month
      intervals (2005, 2010, and 2015) were included. MAIN OUTCOME MEASURES: The
      primary outcomes measured was the rate of complications relating to postoperative
      hemorrhage or thromboembolism. RESULTS: One thousand one hundred twenty-six
      patients underwent major colorectal and abdominal wall surgery (mean age, 61.4
      years (SD 16.3); 575 (51.1%) male). Overall, 229 (21.7%) patients were on
      anticoagulant/antiplatelet agents; there was an increase in the proportion of
      patients on clopidogrel, dual antiplatelet therapy, and novel oral anticoagulants
      over the decade. One hundred seven (9.5%) cases were complicated by
      hemorrhage/thromboembolism. Aspirin (OR, 2.22; 95% CI, 1.38-3.57),
      warfarin/enoxaparin (OR, 3.10; 95% CI, 1.67-5.77), and dual antiplatelet therapy
      (OR, 2.99; 95% CI, 1.37-6.53) were most implicated with complications on
      univariate analysis. Patients with atrial fibrillation (adjusted OR 2.67; 95% CI,
      1.47-4.85), ischemic heart disease (adjusted OR, 2.14; 95% CI, 1.04-4.40), and
      mechanical valves (adjusted OR, 7.40; 95% CI 1.11-49.29) were at increased risk
      of complications on multivariate analysis. The severity of these events was
      mainly limited to Clavien-Dindo 1 (n = 37) and 2 (n = 46) complications.
      LIMITATIONS: This is a retrospective study with incomplete documentation of blood
      loss and operative time in the early study period. CONCLUSIONS: One in ten
      patients incurs hemorrhagic/thromboembolic complications following colorectal and
      abdominal wall surgery. "High-risk" patients are identifiable, and individualized
      management of these patients concerning multidisciplinary discussion and critical
      care monitoring may help improve outcomes. Prospective studies are required to
      formalize protocols in these "high-risk" patients. See Video Abstract at
      http://links.lww.com/DCR/A747.

PMID- 30239397
TI  - Patient and Physician Preferences for Nonoperative Management for Low Rectal
      Cancer: Is It a Reasonable Treatment Option?
AB  - BACKGROUND: Although the body of evidence supporting nonoperative management for
      rectal cancer has been accumulating, there has been little systematic
      investigation to explore how physicians and patients value the tradeoffs between
      oncologic and functional outcomes after abdominal perineal resection and
      nonoperative management. OBJECTIVE: The purpose of this study was to elicit
      patient and physician preferences for nonoperative management relative to
      abdominal perineal resection in the setting of low rectal cancer. DESIGN: We
      conducted a standardized interviews of patients and a cross-sectional survey of
      physicians. SETTINGS: Patients from 1 tertiary care center and physicians from
      across Canada were included. PATIENTS: The study involved 50 patients who were
      previously treated for rectal cancer and 363 physicians who treat rectal cancer.
      INTERVENTIONS: Interventions included standardized interviews using the threshold
      technique with patients and surveys mailed to physicians. MAIN OUTCOMES MEASURES:
      We measured absolute increase risk in local regrowth and absolute decrease in
      overall survival that patients and physicians would accept with nonoperative
      management relative to abdominal perineal resection. RESULTS: Patients were
      willing to accept a 20% absolute increase for local regrowth (ie, from 0% to 20%)
      and a 20% absolute decrease in overall survival (ie, from 80% to 60%) with
      nonoperative management relative to abdominal perineal resection, whereas
      physicians were willing to accept a 5% absolute increase for local regrowth (ie,
      from 0% to 5%) and a 5% absolute decrease in overall survival (ie, from 80% to
      75%) with nonoperative management relative to abdominal perineal resection.
      LIMITATIONS: Data were subject to response bias and generalizable to only a
      select group of patients with low rectal cancer. CONCLUSIONS: Offering
      nonoperative management as an option to patients, even if oncologic outcomes are
      not equivalent, may be more consistent with the values of patients in this
      setting. See Video Abstract at http://links.lww.com/DCR/A688.

PMID- 30239398
TI  - Anal High-Grade Squamous Intraepithelial Lesions in Pharmacologically
      Immunocompromised Patients Followed in a Referral Center.
AB  - BACKGROUND: Information is lacking regarding anal/perianal precancerous lesions
      in referral cohorts of pharmacologically immunocompromised patients. OBJECTIVE:
      The aim of this study is to evaluate the prevalence of anal/perianal high-grade
      squamous intraepithelial lesions in a referral cohort of patients on
      immunomodulator/immunosuppressive medications, who were assessed and followed
      with high-resolution anoscopy. DESIGN: This is a retrospective study. SETTING:
      This study was conducted in a single anal neoplasia service from January 2012 to
      June 2017. PATIENTS: Patients on chronic immunomodulator/immunosuppressive
      medications were included. Cases of concomitant immunosuppression due to HIV
      infection were excluded, and immunosuppression due to chemotherapy was not
      considered for this analysis. INTERVENTION: High-resolution anoscopy was
      performed. MAIN OUTCOME: The primary outcome measured was the prevalence of
      anal/perianal high-grade squamous intraepithelial lesions in a referral cohort of
      pharmacologically immunocompromised patients. RESULTS: Fifty-four patients were
      included, of whom 40 were women (74%), with a mean age of 48 +/- 17 years. A
      total of 232 high-resolution anoscopy examinations were performed in this cohort.
      At the first evaluation, 28 patients (52%) were diagnosed with anal and/or
      perianal high-grade squamous intraepithelial lesions (including 2 cases of
      perianal squamous cell carcinoma); 11 cases (20%) were new diagnoses. Ten of 46
      patients (22%) with follow-up developed a new lesion (high-grade/cancer) during a
      median follow-up period of 17 (interquartile range, 6-28) months. Overall, 37
      patients (69%) in our cohort had anal/perianal high-grade squamous
      intraepithelial lesions ever diagnosed (including previous history, first visit,
      and follow-up); 5 patients had perianal squamous cell carcinoma. At our center,
      6% of the new referrals were known to be pharmacologically immunocompromised
      patients. LIMITATIONS: The retrospective nature of this study, the heterogeneity
      of the cohort, and the absence of human papillomavirus testing were limitations
      of this study. CONCLUSIONS: The presence of anal and/or perianal high-grade
      squamous intraepithelial lesions or cancer detected by high-resolution anoscopy
      in this referral population was high, and the detection of new lesions suggests
      that long-term follow-up is needed. Patients on immunomodulator/immunosuppressive
      drugs represented only a small percentage of the new referrals to our center. See
      Video Abstract at http://links.lww.com/DCR/A748.

PMID- 30239399
TI  - Congenital Infectious Disease and the Neonate.

PMID- 30239402
TI  - Congenital HIV: Prevention of Maternal to Child Transmission.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) is caused by a cytopathic
      lentivirus. HIV without adequate treatment during pregnancy can result in
      maternal to child transmission (MCT) of the virus. Sequelae can include severe
      lifelong morbidities, shorter life expectancies, and high mortality rates without
      antiretroviral therapy. PURPOSE: To discuss epidemiological trends,
      pathophysiology, and clinical care guidelines including those for diagnosis,
      treatment, and management of MCT of HIV in the United States. To emphasize the
      importance of prompt identification, prophylaxis, and treatment of at-risk
      infants. METHODS: PubMed, CINAHL, MEDLINE, and Google Scholar were used to search
      key words-maternal to child transmission, HIV, HIV in pregnancy, and neonatal HIV
      for articles that were relevant and current. The World Health Organization,
      Centers for Disease Control and Prevention, and UNICEF were also utilized for up
      to-date information on the topic. FINDINGS: Timely identification, intervention,
      and treatment are necessary to prevent MCT of HIV. Membrane rupture duration is
      not associated with higher transmission rates with adequate viral suppression.
      IMPLICATIONS FOR PRACTICE: An evidence-based maternal/neonatal collaborative
      approach to care for the prevention and management of MCT of HIV including
      adherence to combined antiretroviral therapy (cART) should be emphasized. Early
      testing, prophylaxis, and treatment for neonates at risk, as well as education on
      current clinical care guidelines for caregivers. IMPLICATIONS FOR RESEARCH:
      Pregnancy complications of cART. MCT rates in conjunction with birthing practices
      and restrictions among women living with HIV with low to undetectable viral
      loads.

PMID- 30239403
TI  - Zika Virus Infection: A Vector-Borne Threat to Pregnant Women and Infants.
AB  - BACKGROUND: Zika virus (ZIKV) is an emergent flavivirus, transmitted
      predominately by Aedes genus mosquitos that recently reached the Americas and was
      soon implicated in an increase in microcephaly and other serious birth defects.
      PURPOSE: This report provides updated information and recommendations on testing,
      screening, and care for pregnant women and infants affected by ZIKV. METHODS:
      Current published recommendations from the Centers for Disease Control and
      Prevention, the World Health Organization, and the American Academy of Pediatrics
      were reviewed and included in this report. RESULTS: Although largely a self
      limiting disease usually without symptoms, pregnant women and their fetuses are
      at greatest risk. Maternal transmission of ZIKV to the fetus can lead to
      congenital Zika infection with potentially devastating sequelae to the infant.
      The available evidence suggests that infection during the first trimester of
      pregnancy, in which the fetus' central nervous system is being formed, is
      associated with higher risk of brain abnormalities and perinatal loss.
      IMPLICATIONS FOR PRACTICE: Uncertainties remain about the course of the disease,
      and the full spectrum of effects of the virus on the developing infant is not yet
      understood. Infants with congenital Zika syndrome need coordinated follow-up and
      long-term specialty care, as well as support for the family. IMPLICATIONS FOR
      RESEARCH: There is no known cure for ZIKV infection and no vaccine is currently
      available. The full spectrum of developmental disabilities and other adverse
      early childhood outcomes associated with congenital ZIKV infection needs to be
      studied.

PMID- 30239404
TI  - Zika Virus: Patient Education Recommendations.
AB  - BACKGROUND: A growing threat to maternal-fetal health, the most recent and
      largest outbreak of the Zika virus disease has introduced the devastating fetal
      effects of microcephaly and other central nervous system deficits. PURPOSE: This
      brief outlines a history of Zika virus disease, its known effects, best practice
      recommendations for providers to educate patients, and information for
      individuals on how to protect themselves. METHODS/SEARCH STRATEGY: A search of
      the literature using the databases PubMed, UptoDate, and CINAHL was conducted for
      articles published between 2009 and 2016. Key informant interviews with clinical
      genetics and public health professionals were conducted. FINDINGS/RESULTS: The
      proposed best practice recommendations for education regarding the Zika virus
      disease and appropriate prevention and treatment methods are outlined.
      IMPLICATIONS FOR PRACTICE: As the Zika virus continues to spread and further
      research is conducted regarding its teratogenic effects, the need for concise and
      effective education is critical to raise awareness, decrease the potential for
      maternal exposure, and reduce fetal risks. IMPLICATIONS FOR RESEARCH: Therefore,
      the need for appropriate recognition, treatment, management, and prevention of
      the Zika virus disease prompts the necessity for further education and high
      quality level research to be conducted and utilized.

PMID- 30239405
TI  - Correlation of Premature Infant Sleep/Wakefulness and Noise Levels in the
      Presence or Absence of "Quiet Time".
AB  - BACKGROUND: Peak sound levels during sleep can compromise the development of
      hospitalized infants. Quiet time is a strategy implemented in neonatal units to
      promote the sleeping of neonates by reducing noise levels, luminosity, and
      handling during particular periods of the day. PURPOSE: To determine the impact
      of quiet time on reducing sound levels and increasing total sleep time. METHODS:
      This longitudinal study was conducted at a neonatal intermediate care unit with a
      convenience sample of 12 premature infants. Four times per day, 60-minute quiet
      times were provided in the neonatal unit. Sleep-awake states and sound levels
      were evaluated during quiet times as well as 60 minutes before and afterward.
      Polysomnography was used for sleep-awake state assessment, and a noise dosimeter
      was used to check sound levels every 24 hours. RESULTS: The preterm infants had a
      corrected gestational age of 35.0 +/- 1.5 weeks and weighed 1606.0 +/- 317.8 g.
      Total sleep time was highest during quiet time (P = .005). Premature infants
      remained awake for longer following quiet times (P = .005). There was also a
      reduction in sound level during quiet times compared with the other time frames
      (P = .006). No statistically significant relationship was found between total
      sleep time and sound levels more than 24 hours. IMPLICATIONS FOR PRACTICE: Quiet
      time is a nursing intervention that should be implemented in all neonatal units.
      IMPLICATIONS FOR RESEARCH: Future research should use a greater sample size and
      other factors that influence sleep should be further investigated.

PMID- 30239406
TI  - Congenital Tuberculosis: A New Concern in the Neonatal Intensive Care Unit.

PMID- 30239407
TI  - Psychometric Properties of the Early Feeding Skills Assessment Tool.
AB  - BACKGROUND: Supporting infants as they develop feeding skills is an essential
      component of neonatal and pediatric care. Selecting appropriate and supportive
      interventions begins with a thorough assessment of the infant's skills. The Early
      Feeding Skills (EFS) tool is a clinician-reported instrument developed to assess
      the emergence of early feeding skills and identify domains in need of
      intervention. PURPOSE: The purpose of this study was to identify the factor
      structure of the EFS and test its psychometric properties, including internal
      consistency reliability and construct validity. METHODS: EFS-trained
      interprofessional clinicians in 3 settings scored 142 feeding observations of
      infants 33 to 50 weeks' postmenstrual age. Redundant and rarely endorsed items
      were removed. Factor analysis methods clustered items into subscales. Construct
      validity was examined through the association of the EFS with (1) concurrently
      scored Infant-Driven Feeding Scale-Quality (IDFS-Q), (2) infant birth risk
      (gestational age), and (3) maturity (postmenstrual age). RESULTS: Principal
      components analysis with varimax rotation supported a 5-factor structure. The
      total EFS demonstrated good internal consistency reliability (Cronbach alpha=
      0.81). The total EFS score had construct validity with the IDFS-Q (r =-0.73; P <
      .01), and with gestational age of a subsample of premature infants (r = 0.22; P <
      .05). IMPLICATIONS FOR PRACTICE: As a valid and reliable tool, the EFS can assist
      the interprofessional feeding team to organize feeding assessment and plan care.
      IMPLICATIONS FOR RESEARCH: The strong psychometric properties of the EFS support
      its use in future research.

PMID- 30239408
TI  - Personalization of arterial pressure in the perioperative period.
AB  - PURPOSE OF REVIEW: This review aims to discuss recent findings on the
      relationship between intraoperative arterial hypotension and organ dysfunction in
      surgical patients and examines the available evidence for personalizing blood
      pressure (BP) management as a strategy to improve patient outcome. RECENT
      FINDINGS: Hypotension contributes to oxygen supply-demand mismatch and may cause
      an ischemia-reperfusion injury which may manifest as organ dysfunction. Evidence
      is accumulating suggesting that hypotension is associated with acute
      postoperative myocardial and kidney injury, and increased risk of mortality in
      surgical patients. In contrast to traditional BP management in which BP targets
      are empirically chosen, personalized BP management aims at individualizing BP
      targets according to individual patient physiology considering clinical
      conditions that may influence organ pressure-flow autoregulation. Recent
      randomized data provide clinically meaningful findings that a treatment strategy
      aims at targeting individualized BP values which may help improving outcome in
      surgical patients. SUMMARY: Hypotension is a common complication in surgical
      patients and is an important trigger of organ injury in surgical patients.
      Personalized BP management may contribute at reducing postoperative organ
      dysfunction in surgical patients.

PMID- 30239409
TI  - Continuous renal replacement therapy: individualization of the prescription.
AB  - PURPOSE OF REVIEW: Continuous renal replacement therapy (CRRT) is now the
      mainstay of renal organ support in the critically ill. As our understanding of
      CRRT delivery and its impact on patient outcomes improves there is a focus on
      researching the potential benefits of tailored, patient-specific treatments to
      meet dynamic needs. RECENT FINDINGS: The most up-to-date studies investigating
      aspects of CRRT prescription that can be individualized: CRRT dose, timing, fluid
      management, membrane selection, anticoagulation and vascular access are reviewed.
      The use of different doses of CRRT lack conventional high-quality evidence and
      importantly studies reveal variation in assessment of dose delivery. Research
      reveals conflicting evidence for clinicians in distinguishing which patients will
      benefit from 'watchful waiting' vs. early initiation of CRRT. Both dynamic CRRT
      dosing and precision fluid management using CRRT are difficult to investigate and
      currently only observational data supports individualization of prescriptions.
      Similarly, individualization of membrane choice is largely experimental. SUMMARY:
      Clinicians have limited evidence to individualize the prescription of CRRT. To
      develop this, we need to understand the requirements for renal support for
      individual patients, such as electrolyte imbalance, fluid overload or clearance
      of systemic inflammatory mediators to allow us to target these abnormalities in
      appropriately designed randomized trials.

PMID- 30239410
TI  - Community-acquired pneumonia as an emergency condition.
AB  - PURPOSE OF REVIEW: Despite the improvements in its management, community-acquired
      pneumonia (CAP) still exhibits high global morbidity and mortality rates,
      especially in elderly patients. This review focuses on the most recent findings
      on the epidemiology, cause, diagnosis and management of CAP. RECENT FINDINGS:
      There is consistent evidence that the trend in CAP mortality has declined over
      time. However, the mortality of pneumococcal CAP has not changed in the last two
      decades, with an increase in the rate of hospitalization and more severe forms of
      CAP. Streptococcus pneumoniae remains the most frequent cause of CAP in all
      settings, age groups and regardless of comorbidities. However, the implementation
      of molecular diagnostic tests in the last years has identified respiratory
      viruses as a common cause of CAP too. The emergency of multidrug-resistance
      pathogens is a worldwide concern. An improvement in our ability to promptly
      identify the causative cause of CAP is required in order to provide pathogen
      directed antibiotic therapy, improve antibiotic stewardship programs and
      implement appropriate vaccine strategies. SUMMARY: It is time to apply all the
      knowledge generated in the last decade in order to optimize the management of
      CAP.

PMID- 30239411
TI  - CRRT for sepsis-induced acute kidney injury.
AB  - PURPOSE OF REVIEW: Sepsis-induced acute kidney injury (SI-AKI) represents the
      first cause of AKI in ICUs, and renal replacement therapy (RRT) is frequently
      applied in advanced AKI stages. The debate between 'rescue' indications for RRT
      start in patients with severe AKI (acidosis, hyperkalemia, uremia,
      oliguria/anuria, volume overload) and a proactive RRT initiation is still
      ongoing. In addition, current SI-AKI pathophysiologic theory has identified the
      toxic effects of soluble middle-molecules released during sepsis and inflammation
      (pathogen and damaged associated molecular patterns).The purpose of the present
      review is to summarize the recent literature on RRT for patients with SI-AKI.
      Supportive or replacement measures for severe stages of renal dysfunction and
      blood purification techniques for sepsis syndrome will be reviewed. RECENT
      FINDINGS: Anticipated RRT for SI-AKI does not seem to improve survival or renal
      recovery. There is no clinical advantage by delivering continuous RRT at high
      doses for blood purification purposes. Similarly, specific applications with
      dedicated devices and membranes have yielded no clinical benefit in these
      patients, so far. SUMMARY: In the present review, the recent insights and results
      from large randomized and nonrandomized trials in the area of RRT applied both as
      supportive measures for kidney failure and blood purification techniques are
      described.

PMID- 30239412
TI  - Updates in emergency airway management.
AB  - PURPOSE OF REVIEW: Historically, most evidence supporting emergency airway
      management strategies have been limited to small series, retrospective analyses
      and extrapolation from other settings (i.e. the operating room). Over the past
      year, several large, randomized clinical trials have offered new findings to
      inform emergency airway management techniques. RECENT FINDINGS: One large,
      randomized clinical trial, found improved first attempt success rates with bougie
      facilitated intubation compared with traditional intubation. Two randomized
      clinical trials suggested better outcomes in adult out-of-hospital cardiac arrest
      (OHCA) with supraglottic airways (SGA) than intubation. A randomized clinical
      trial in OHCA patients could not identify outcome differences between
      endotracheal intubation (ETI) and bag-valve mask (BVM) ventilation but suggested
      higher rates of aspiration with BVM. SUMMARY: These studies offer new findings to
      inform the practice of emergency airway management. Bougie use should be
      considered as a first-line approach in emergency intubation. SGA-based strategies
      should be considered as a first-line approach in the management of OHCA.

PMID- 30239413
TI  - The conundrum of recurrent low-grade tumours: to treat or to observe?
AB  - PURPOSE OF REVIEW: To describe the importance of risk stratification and the role
      of more conservative management like office fulguration, office laser ablation
      and active surveillance in recurrent low-grade Ta tumours. RECENT FINDINGS:
      Updated models have been designed for risk stratification of intermediate-risk
      tumours. Conservative forms of management like office fulguration or laser
      ablation and even active surveillance seem well tolerated; however, randomized,
      controlled trials are lacking. In patients who have been tumour free for 5 years,
      late recurrences have been described. SUMMARY: Recurrent low-grade Ta tumours are
      classified in the intermediate risk group, which is a heterogeneous group.
      Therefore, risk stratification should be done by updated models or patients
      should be stratified in a risk group sub-classification. Recurrent low-grade Ta
      patients have a favourable prognosis and consequently are prone to overtreatment.
      Office fulguration or laser ablation or even active surveillance could be
      implemented in strictly selected patients. For active surveillance, Miyake et al.
      proposed a helpful flowchart with criteria for patient selection and for
      intervention. Follow up using cystoscopy and cytology is essential, but an
      optimal scheme has not been identified. As late recurrences are not infrequent
      and recurrent low-grade Ta patients can even die from bladder cancer, long term
      follow-up should be performed yearly, by cystoscopy and cytology.

PMID- 30239414
TI  - MRI to guide biopsies or avoid biopsies?
AB  - PURPOSE OF REVIEW: To discuss contemporary data on the value of multiparametric
      MRI (mpMRI) for guiding the decision to biopsy men at risk for prostate cancer,
      as well as its utility in active surveillance programs. RECENT FINDINGS: Although
      a systematic 12-core biopsy is the current standard of care for men with
      increased suspicion for prostate cancer, MRI with or without targeted biopsy has
      been shown to reliably improve the detection of clinically significant disease
      following a prior negative biopsy. At the same time, there is a growing body of
      evidence to support the use of MRI for diagnostic purposes in biopsy-naive
      patients, as well for enrolling and monitoring men on active surveillance
      programs. SUMMARY: mpMRI is an evolving technology with great promise for
      altering our approach to prostate cancer diagnosis and surveillance. In
      conjunction with targeted biopsies, MRI offers greater specificity for the
      detection of clinically significant cancer and therefore may help to reduce
      overdetection of indolent disease while minimizing the risks and limitations of
      systematic biopsies.

PMID- 30239415
TI  - Focal therapy of prostate cancer.
AB  - PURPOSE OF REVIEW: The aim of this study was to summarize the latest evidence, as
      well as the rationale behind using focal therapy for the treatment of prostate
      cancer. With patients becoming more educated, knowledge of the available evidence
      is key when discussing treatment. RECENT FINDINGS: In older works, the natural
      history of prostate cancer has been described as being multifocal, driven by one
      index lesion. This represents the key argument for most experts, why focal
      therapy is feasible in prostate cancer. Most modalities have similar results. For
      high-intensity focussed ultrasound (HIFU), a pooled data analysis with a median
      follow-up of 2.2 years showed a negative biopsy rate of 77% with a salvage
      therapy free rate of 92%. A matched pair analysis comparing irreversible
      electroporation with robot-assisted radical prostatectomy showed a better side
      effect profile for focal therapy in evenly matched groups, yet with worse disease
      free survival. Interestingly, the better outcomes concerning continence and
      erectile function did not translate into better patient-reported outcomes.
      SUMMARY: Focal therapy modalities are generally well tolerated and show good
      results in terms of continence and potency. Long-term follow-up is not available,
      and inclusion criteria for trials are not yet uniform. Newer technologies, such
      as photodynamic therapy, are being developed, as well as improvements to older
      techniques, such as HIFU.

PMID- 30239416
TI  - Three-dimensional localization and targeting of prostate cancer foci with imaging
      and histopathologic correlation: establishing a multidisciplinary team for
      quality improvement.
AB  - PURPOSE OF REVIEW: The current trend in image-based identification and
      characterization of prostate cancer (PCa) utilizing multiparametric MRI (mpMRI)
      has affected diagnostic and treatment planning in terms of targeted biopsy, risk
      stratification and prognostic evaluation, clinical management and follow-up.
      However, the accuracy of MRI to detect clinically significant disease is variable
      between different institutions. The role of quality control initiatives to
      increase the concordance between clinical-imaging-histopathological data and to
      improve accurate targeting of the suspicious lesions cannot be overemphasized.
      This article describes the approaches to correlate mpMRI findings with
      histopathology and the role of multidisciplinary teams for quality improvement
      and feedback interventions. RECENT FINDINGS: Validating the mpMRI and image
      targeted fusion biopsy findings with prostatectomy specimen histopathology as the
      gold standard is essential for assessment of the concordance between clinical
      imaging-histopathological data. Utilization of a MRI-derived patient-specific
      prostate mold enables a direct comparison between histopathological versus
      imaging characteristics of cancer foci in the same sectional plane of the
      specimen versus MRI. Furthermore, 'reverse fusion' technology provides the
      ability to audit the quality of targeting following fusion biopsy. SUMMARY: The
      development of a multidisciplinary team approach with group discussions,
      workflows to integrate and correlate clinical, imaging and histological data, as
      well as feedback and audit interventions can improve the quality of care when an
      image-based PCa diagnostic program is implemented. This needs to be executed at
      the local level to better understand each institutions' performance
      characteristics of mpMRI and image-targeted intervention.

PMID- 30239417
TI  - Focal therapy of prostate and kidney cancer.

PMID- 30239418
TI  - Sepsis Increases Muscle Proteolysis in Severely Burned Adults, But Does Not
      Impact Whole-Body Lipid or Carbohydrate Kinetics.
AB  - Sepsis is a common and often fatal consequence of severe burn injury, but its
      exact effects on whole body and muscle metabolism in the burn patient is unclear.
      To address this, 13 septic and 11 nonseptic patients (age: 36.9 +/- 13.0 years)
      with burns encompassing >30% of their total body surface area underwent muscle
      protein kinetic studies under postabsorptive conditions using bolus injections of
      ring-C6 and N phenylalanine isotopes. In parallel, whole-body lipid and
      carbohydrate kinetics were assessed using constant infusions of [U-C6]palmitate,
      [6,6-H2]glucose, and [H5]glycerol, and during a 2-h hyperinsulinemic euglycemic
      clamp. Muscle mRNA levels of genes implicated in the development of muscle
      cachexia were assessed by qPCR. Fractional breakdown rates of mixed-muscle
      proteins were found to be 2.4-fold greater in septic versus nonseptic patients (P
      < 0.05). No discernable differences in fractional synthetic rate of mixed-muscle
      proteins or rate of appearance of plasma free fatty acids, glycerol, or glucose
      could be observed between patient groups, although the latter was significantly
      associated with burn size (P < 0.05). Hyperinsulinemia stimulated whole-body
      glucose uptake and suppressed endogenous glucose production and whole-body
      lipolytic rate to equivalent degrees in both groups. Muscle mRNA levels of genes
      spanning autophagy, lysosomal, and ubiquitin proteasome-mediated proteolysis were
      not enhanced in septic versus nonseptic patients. Our results demonstrate that
      accelerated muscle proteolysis appears to be the principal metabolic consequence
      of sepsis in severe burn patients and could be a contributing factor to the
      accelerated loss of muscle mass in these individuals. The exact mechanistic basis
      for these changes remains unclear.

PMID- 30239419
TI  - Myocardial Electrical Remodeling and the Arrhythmogenic Substrate in Hemorrhagic
      Shock-Induced Heart: Anti-Arrhythmogenic Effect of Liposome-Encapsulated
      Hemoglobin (HbV) on the Myocardium.
AB  - INTRODUCTION: Prolonged low blood pressure < 40 mmHg in hemorrhagic shock (HS)
      causes irreversible heart dysfunction, "Shock Heart Syndrome" (SHS), which is
      associated with lethal arrhythmias (VT/VF) leading to a poor prognosis. METHODS:
      To investigate whether the liposome-encapsulated human hemoglobin oxygen carrier
      (HbV) is comparable in effectiveness to autologous washed red blood cells (wRBCs)
      for improving arrhythmogenic properties in SHS, optical mapping analysis (OMP),
      electrophysiological study (EPS), and pathological examinations were performed in
      Sprague-Dawley rat hearts obtained from rats subjected to acute HS by withdrawing
      30% of total blood volume. After acute HS, the rats were immediately resuscitated
      by transfusing exactly the same amount of saline (SAL), 5% albumin (5%ALB), HbV,
      or wRBCs. After excising the heart, OMP and EPS were performed in Langendorff
      perfused hearts. RESULTS: OMP showed a tendency for abnormal conduction and
      significantly impaired action potential duration dispersion (APDd) in both
      ventricles with SAL and 5%ALB. In contrast, myocardial conduction and APDd were
      substantially preserved with HbV and wRBCs. Sustained VT/VF was easily provoked
      by a burst pacing stimulus to the left ventricle with SAL and 5%ALB. No VT/VF was
      induced with HbV and wRBCs. Pathology showed myocardial structural damage
      characterized by worse myocardial cell damage and Connexin43 with SAL and 5%ALB,
      whereas it was attenuated with HbV and wRBCs. CONCLUSIONS: Ventricular structural
      remodeling after HS causes VT/VF in the presence of APDd. Transfusion of HbV
      prevents VT/VF, similarly to transfusion of wRBCs, by preventing electrical
      remodeling and preserving myocardial structures in HS-induced SHS.

PMID- 30239420
TI  - " Immunosuppression " is Inappropriately Qualifying the Immune Status of Septic
      and Sirs Patients.
AB  - Immunosuppression is the most commonly used concept to qualify the immune status
      of patients with either sterile systemic inflammatory response syndrome (SIRS) or
      sepsis. In this review we attempt to demonstrate that the concept of
      immunosuppression is an oversimplification of the complex anti-inflammatory
      response that occurs in patients dealing with a severe sterile or infectious
      insult. Particularly, the immune status of leukocytes varies greatly depending on
      the compartment from where they are derived from. Furthermore, while certain
      functions of immune cells present in the blood stream or in the hematopoietic
      organs can be significantly diminished, other functions are either unchanged or
      even enhanced. This juxtaposition illustrates that there is no global defect. The
      mechanisms called reprogramming or trained innate immunity are probably aimed at
      preventing a generalized deleterious inflammatory reaction, and work to maintain
      the defense mechanisms at their due levels.

PMID- 30239421
TI  - Late Peaks of HMGB1 and Sepsis Outcome: Evidence for Synergy With Chronic
      Inflammatory Disorders.
AB  - High mobility group box 1 (HMGB1) is released from macrophages as a late
      biomarker of sepsis. Conditions associated with pre-existing macrophage
      activation may modify HMGB1 expression. This study aimed to assess the impact of
      HMGB1 kinetics on 28-day mortality. In a sub-study of a previous randomized
      clinical trial among patients with SIRS and Gram-negative infections, patients
      were classified in early and late HMGB1 peak groups. Serial measurements of
      HMGB1, ferritin and interferon-gamma (IFNgamma) were performed in all available
      sera. Two hundred and ten patients were included; 118 (46.5%) had at least one
      inflammatory disease (diabetes, chronic obstructive pulmonary disease, chronic
      heart failure or chronic renal disease). Mortality after 28 days was higher among
      patients with a late peak of HMGB1 (OR 2.640; p = 0.026). Co-existence of late
      peak and inflammatory disease synergistically impacted mortality (odds ratio of
      logistic regression analysis 3.17; p: 0.027). Late peak was concomitantly
      associated with higher values of ferritin (p = 0.035), and IFNgamma (p = 0.002)
      among patients with hyperferritinemia. It is concluded that late HMGB1 peak was
      associated with worse prognosis, especially in patients with underlying chronic
      inflammatory conditions.

PMID- 30239422
TI  - A Preliminary Study of the Effect of Early Aerobic Exercise Treatment for Sport
      Related Concussion in Males.
AB  - OBJECTIVE: To study the effect of early prescribed aerobic exercise versus
      relative rest on rate of recovery in male adolescents acutely after sport-related
      concussion (SRC). DESIGN: Quasi-experimental design. SETTING: University sports
      medicine centers. PARTICIPANTS: Exercise group (EG, n = 24, 15.13 +/- 1.4 years,
      4.75 +/- 2.5 days from injury) and rest group (RG, n = 30, 15.33 +/- 1.4 years,
      4.50 +/- 2.1 days from injury). INTERVENTIONS: Exercise group performed a
      progressive program of at least 20 minutes of daily subthreshold aerobic
      exercise. Rest group was prescribed relative rest (no structured exercise). Both
      groups completed daily online symptom reports (Postconcussion Symptom Scale) for
      14 days. MAIN OUTCOME MEASURES: Days to recovery after treatment prescription.
      Recovery was defined as return to baseline symptoms, exercise tolerant, and
      judged recovered by physician examination. RESULTS: Recovery time from initial
      visit was significantly shorter in EG (8.29 +/- 3.9 days vs 23.93 +/- 41.7 days,
      P = 0.048). Mixed-effects linear models showed that all symptom clusters
      decreased with time and that there was no significant interaction between
      treatment group and time. No EG participants experienced delayed recovery (>30
      days), whereas 13% (4/30) of RG participants experienced delayed recovery.
      CONCLUSIONS: These preliminary data suggest that early subthreshold aerobic
      exercise prescribed to symptomatic adolescent males within 1 week of SRC hastens
      recovery and has the potential to prevent delayed recovery.

PMID- 30239423
TI  - Effects of D-alpha-tocopherol polyethylene glycol succinate-emulsified
      poly(lactic-co-glycolic acid) nanoparticles on the absorption, pharmacokinetics,
      and pharmacodynamics of salinomycin sodium.
AB  - Although salinomycin sodium (SS) has shown in-vitro potential to inhibit cancer
      stem cell growth and development, its low water solubility makes it a poor
      candidate as an oral chemotherapeutic agent. To improve the bioavailability of
      SS, SS was encapsulated here using D-alpha-tocopherol polyethylene glycol
      succinate (TPGS)-emulsified poly(lactic-co-glycolic acid) (PLGA) nanoparticles
      and compared with its parent SS in terms of absorption, pharmacokinetics, and
      efficacy in suppressing nasopharyngeal carcinomas stem cells. The
      pharmacokinetics of SS and salinomycin sodium-loaded D-alpha-tocopherol
      polyethylene glycol succinate-emulsified poly(lactic-co-glycolic acid)
      nanoparticles (SLN) prepared by nanoprecipitation were analyzed in-vivo by timed
      interval blood sampling and oral administration of SS and SLN to rats. Sensitive
      liquid chromatography-mass spectrometry (LC-MS) was developed to quantify plasma
      drug concentrations. SS and SLN transport in Caco-2 cells was also investigated.
      The therapeutic efficacy of SS and SLN against cancer stem cells was determined
      by orally administering the drugs to mice bearing CNE1 and CNE2 nasopharyngeal
      carcinoma xenografts and then evaluating CD133 cell proportions and tumorsphere
      formation. The in-vivo trial with rats showed that the Cmax, AUC(0-t), and Tmax
      for orally administered SLN were all significantly higher than those for SS
      (P<0.05). These findings were corroborated by a Caco-2 cell Transwell assay
      showing that relative SLN absorption was greater than that of SS on the basis of
      their apparent permeability coefficients (Papp). Significantly, therapeutic SLN
      efficacy against nasopharyngeal carcinoma stem cells was superior to that of SS.
      TPGS-emulsified PLGA nanoparticles effectively increase SS solubility and
      bioavailability. SLN is, therefore, promising as an oral chemotherapeutic agent
      against cancer stem cells.

PMID- 30239424
TI  - The nervous system: a new target in the fight against cancer.
AB  - During cancer progression, tumor cells interact with the neighboring environment,
      including neuronal tissue. The important influence of the nervous system on
      growth and metastasis of cancer is now widely accepted. As such, using
      medications that traditionally target the nervous system may be an avenue toward
      treating cancer. The focus of this review is to detail how several classes of
      medications, traditionally used to treat nervous system disorders, impact cancer.
      Specifically, we review the preclinical and clinical evidence that support the
      use of anti-beta-adrenergic, anticholinergic, antipsychotic, and antidepressant
      medications to treat some cancers. In addition, we discuss the use of ablative
      modalities, such as physical and chemical denervation, to treat cancer or protect
      against cancer development. Using the medications that target the nervous system
      to treat cancer is a promising addition to an existing therapy or an alternative
      treatment strategy. Furthermore, rapidly expanding basic science research in this
      area will likely yield novel cancer therapies that work by targeting the nervous
      system.

PMID- 30239425
TI  - Effects of Low- and High-Mineral Content Water on the Relative Bioavailability of
      a Coformulated Abacavir/Dolutegravir/Lamivudine Dispersible Tablet in Healthy
      Adults.
AB  - BACKGROUND: The fixed-dose combination (FDC) tablet formulation of
      abacavir/dolutegravir/lamivudine is indicated for the treatment of HIV-1
      infection in adults and pediatric patients weighing >=40 kg. Alternative
      formulations with acceptable palatability and convenient dosing are needed for
      children who require smaller doses and have difficulty swallowing tablets.
      SETTING: A phase 1, open-label, randomized study was conducted in healthy adults
      to evaluate the relative bioavailability of a novel dispersible FDC tablet of
      abacavir 150 mg/dolutegravir 10 mg/lamivudine 75 mg administered under 4
      different dosing conditions compared with dolutegravir plus abacavir/lamivudine
      nondispersible, film-coated tablets. METHODS: The test treatments were 4
      dispersible FDC tablets reconstituted in water with high- or zero-mineral content
      and administered either immediately or after a 30-minute delay. The reference
      treatment was 4 nondispersible dolutegravir 10-mg tablets plus 1 nondispersible
      abacavir 600-mg/lamivudine 300-mg tablet administered with zero-mineral content
      water. The primary endpoints were area under the concentration-time curve from
      time 0 extrapolated to infinity and the maximum observed plasma concentration.
      RESULTS: Following administration of dispersible
      abacavir/dolutegravir/lamivudine, the relative bioavailability of dolutegravir
      was approximately 50% higher. Abacavir and lamivudine demonstrated bioequivalence
      when administered as the dispersible FDC tablet compared with coadministration of
      dolutegravir plus abacavir/lamivudine nondispersible, film-coated tablets.
      Neither the mineral content of the water nor dosing times affected the
      pharmacokinetics of individual components. The dispersible tablet was safe and
      well tolerated, and the palatability was acceptable. CONCLUSIONS: These
      pharmacokinetic results support further development of a dispersible FDC tablet
      of abacavir/dolutegravir/lamivudine for future use in pediatric patients.

PMID- 30239427
TI  - Necrotizing Otitis Externa-Analysis of 83 Cases: Clinical Findings and Course of
      Disease.
AB  - OBJECTIVES: Evaluate the relationship between clinical findings and course of
      disease among patients with necrotizing otitis externa (NOE). STUDY DESIGN:
      Retrospective case series review. SETTING: Tertiary referral center. PATIENTS:
      Adult patients with no previous history of chronic ear disease, hospitalized due
      to NOE between the years 1990 to 2015. MAIN OUTCOME MEASURES: 1) Duration of
      hospitalization and 2) necessity for surgery. RESULTS: Eighty-one patients were
      included in the study, corresponding to 83 effected ears. Thirty-two patients
      (38.5%) were hospitalized longer than 20 days and 20 patients (24.0%) underwent
      surgery. Otalgia was the most common complaint (n = 71, 85.5%). Pseudomonas
      Aeruginosa (PA) was the most common isolated bacteria (n = 40, 48.1%). Shifting
      incidence of culture results was noted, as rates of PA NOE decreased and rates of
      sterile culture and fungal NOE increased. Duration of complaints and presence of
      aural discharge at admission were associated with prolonged hospitalization (p =
      0.010, p = 0.011, respectively). Advanced age, duration of hospitalization, and
      rates of readmission were associated with surgery (p = 0.037, p < 0.001, p <
      0.001 respectively). CONCLUSIONS: Duration of complaints and presence of aural
      discharge may indicate advanced NOE and require longer in-hospital treatment.
      Elderly patients are at increased risk for conservative treatment failure and are
      more likely to require surgery. With shifting incidence of pathogens, a wider
      empirical treatment covering nontraditional pathogens should be considered.

PMID- 30239428
TI  - Systematic Review of Facial Nerve Outcomes After Middle Fossa Decompression and
      Transmastoid Decompression for Bell's Palsy With Complete Facial Paralysis.
AB  - OBJECTIVES: The surgical timing and approach for patients with Bell's palsy and
      complete facial paralysis is controversial. A previous meta-analysis demonstrated
      no benefit from surgical decompression, however, only transmastoid decompression
      (TMD) was investigated. No study has evaluated both the outcomes of TMD and
      middle fossa decompression (MFD). STUDY DESIGN: Systematic review with meta
      analysis. METHODS: A systematic literature search identifying all studies meeting
      inclusion criteria and published between 1985 and 2015 was performed. Final House
      Brackmann (HB) scores were calculated and compared for TMD, MFD, and medical
      controls. A meta-analysis was performed to compare MFD less than or equal to 14
      days versus MFD more than 14 days, TMD versus medical controls, and surgical
      therapy (combined MFD and TMD) versus medical controls. Observational studies
      without a control arm were excluded from the meta-analysis. RESULTS: Average HB
      scores for MFD less than or equal to 14 days was 1.8, MFD more than 14 days was
      2.75, and MFD medical controls was 2.4. For TMD average HB was 2.3 and for TMD
      medical controls average HB was 2.4. 75% MFD were performed within 14 days of
      onset while TMD was performed between 15 and 120 days. Meta-analysis demonstrated
      significantly better facial nerve outcomes for MFD performed less than or equal
      to 14 days versus more than 14 days (p < 0.001), but no difference between TMD
      versus medical controls (p = 0.78) or surgical therapy versus medical controls (p
      = 0.58). CONCLUSION: MFD performed within 14 days of symptom onset results in
      better facial nerve outcomes than MFD performed after 14 days. TMD does not offer
      improved outcomes over medical management however decompression was only offered
      after 15 days of symptom onset.

PMID- 30239426
TI  - Impact of Partner-Related Social Harms on Women's Adherence to the Dapivirine
      Vaginal Ring During a Phase III Trial.
AB  - BACKGROUND: Long-acting female-initiated methods such as the dapivirine ring may
      give women greater agency in HIV-1 prevention. However, social harms, defined as
      nonmedical adverse consequences of study participation or dapivirine ring use,
      may reduce product adherence and consequently HIV-1 protection. METHODS: We
      assessed whether experiencing social harms from male partners was associated with
      lower adherence to the dapivirine ring in the MTN-020/ASPIRE trial. Reports of
      social harms were solicited quarterly. Low adherence was defined by plasma
      dapivirine levels <=95 pg/mL or residual dapivirine levels in returned rings
      >23.5 mg. RESULTS: Among 2629 women enrolled in ASPIRE, 85 (3.2%) reported 87
      social harms during a median follow-up of 1.6 years. Women were significantly
      more likely to have low adherence, measured by plasma dapivirine levels, at
      visits with a social harm in the past month than at visits where no social harm
      was reported (adjusted risk ratio 2.53, 95% confidence interval: 1.37 to 4.66, P
      = 0.003). There was no association for social harms reported >=1 month prior,
      suggesting an acute, short-term effect. Women were significantly more likely to
      not return a ring at visits with a social harm reported (adjusted risk ratio
      24.70, 95% confidence interval: 18.57 to 32.85, P < 0.001). In rings that were
      returned, social harms were not associated with residual dapivirine levels.
      CONCLUSIONS: Although social harms were uncommon (<5% of women with >1 year of
      use), participants reporting social harms by male partners had lower adherence to
      the dapivirine ring. Strategies to mitigate nonadherence to product use related
      to social harms should be evaluated in future studies of female-controlled HIV-1
      prevention options.

PMID- 30239429
TI  - Incidence of Functional Nasal Voice in Patients With Patulous Eustachian Tube.
AB  - OBJECTIVE: Some patients with a patulous Eustachian tube (PET) complain of a
      nasal voice. This feature is often dismissed without further investigation. As
      such, there are only a few reports on this important symptom and scant studies
      have been conducted on a sufficiently large number of cases with PET. Therefore,
      this study was undertaken to investigate the characteristics of patients having a
      nasal voice and to examine whether this symptom can be an indication of the
      severity of PET. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center.
      SUBJECTS AND METHODS: A retrospective survey of medical records in Sen-En Rifu
      Hospital identified 85 patients (40 men and 45 women) with PET between 2013 and
      2016. Diagnosis of definite PET was based on the Proposal on Diagnostic Criteria
      of PET announced by the Otological Society of Japan (2017). The questionnaire
      inquired about the presence of a nasal voice and it was distributed to each
      patient at the first visit to the clinic. If a patient marked "yes" for the
      presence of nasal voice, he/she was later asked on the telephone to exclude nasal
      voice ascribable to causes other than PET, such as nasal diseases. Correlation
      between nasal voice and patient characteristics (age, sex, affected side, and PET
      symptoms such as autophony of own voice, aural fullness, and autophony of
      breathing sounds), subjective severity of PET evaluated by patulous Eustachian
      tube handicap inventory-10 (PHI-10), and that with the objective severity of PET
      evaluated by tubo-tympano-aerodynamic-graphy (TTAG) and sonotubometry were
      investigated. RESULTS: Seventy-six patients (36 men and 40 women) with definite
      PET were evaluated in this study. Thirteen patients (17.1%) (five men and eight
      women) reported a nasal voice coinciding with the occurrence of PET symptoms such
      as voice autophony, aural fullness, and breathing autophony. Age, sex, affected
      side, PET symptoms (autophony of their own voice, aural fullness, and autophony
      of their breathing sounds), and objective findings (TTAG and sonotubometry) were
      not significantly different between the two groups. The average total score of
      the PHI-10 in the "PET associated Nasal Voice Group" was 35.8 +/- 4.5, which was
      statistically higher than that of the "non PET associated Nasal Voice Group" 23.6
      +/- 10.7 (p = 0.002). Out of 76 patients, 44 were treated surgically (Kobayashi
      Plug). In the "PET associated Nasal Voice Group," 85% (11 out of 13) were
      subjected to surgical treatment, whereas 52% (33 out of 63) underwent surgical
      treatment in the "non PET associated Nasal Voice Group." The rate of surgical
      treatment was significantly higher in "PET associated Nasal Voice Group" (p =
      0.047). CONCLUSION: Nasal voice due to PET symptoms was observed in 17.1% of PET
      patients. It was generally found in patients with severe subjective symptoms.
      Nasal voice can be an indication of subjective severity. However, this study
      failed to show objective evidence of wider Eustachian tube in such cases.
      Patients with a nasal voice tended to seek vigorous treatment including surgery.

PMID- 30239430
TI  - Ameloblastic Fibroma With an Unusual Location.

PMID- 30239431
TI  - Outcomes of Stapedotomy With Heat-Crimped Prostheses.
AB  - BACKGROUND: Theoretical disadvantages are associated with the use of heat-crimped
      piston prostheses in stapedotomy. Loose crimping could result in prosthesis
      displacement or slippage. Alternatively, overly tight crimping may cause trauma
      to the incus with resultant necrosis. OBJECTIVES: 1) Analyze outcomes of patients
      undergoing stapedotomy with heat-activated piston-style prostheses, and 2)
      compare outcomes between prostheses made by different manufacturers. STUDY
      DESIGN: Retrospective. SETTING: Vanderbilt Medical Center. PATIENTS AND METHODS:
      Cases undergoing stapedotomy between 2005 and 2016 were reviewed. Audiometric
      assessments were recorded in accordance with American Academy of Otolaryngology
      Head and Neck Surgery (AAO-HNS) guidelines. Patients who lacked audiometric
      follow-up before 6 months or after 1 year were excluded. INTERVENTION(S):
      Diagnostic, therapeutic, and rehabilitative. MAIN OUTCOME MEASURE(S):
      Postoperative air-bone gap (ABG) and achievement of an ABG is less than or equal
      to 10 dB. RESULTS: Three hundred fifty-eight patients met inclusion criteria. At
      short-term follow-up (<6 mo), the mean ABG was 11 +/- 8 dB in the entire cohort;
      this did not differ based on manufacturer (p = 0.13). The majority of patients
      (63%) achieved an ABG less than or equal to 10 dB. At longer-term follow-up, the
      mean ABG was 9 +/- 7 dB; again no differences were noted when comparing
      prosthesis manufacturer (p = 0.20). 70% of patients achieved an ABG less than or
      equal to 10 dB at longer-term follow-up. When comparing short- to long-term
      follow-up, ABG did not significantly change over time (p = 0.76). The overall
      revision rate was 1.9% (n = 7). CONCLUSION: Favorable hearing outcomes are
      obtained both short- and long-term following stapedotomy and placement of heat
      crimped piston prostheses. Both prosthesis groups appear stable in the middle ear
      environment long-term, as evidenced by a 1.9% revision rate among them.

PMID- 30239432
TI  - Relationship of a "Fundal Fluid Cap" and Vestibular Schwannoma Volume: Analysis
      of Preoperative Radiographic Findings and Outcomes.
AB  - OBJECTIVE: To evaluate the relationship between radiographic fundal fluid cap in
      the lateral internal auditory canal, preoperative clinical characteristics, and
      postoperative outcomes in patients with vestibular schwannoma who underwent
      microsurgical excision. STUDY DESIGN: Retrospective chart review. SETTING:
      Academic tertiary referral center. PATIENTS: Thirty-six consecutive patients
      (mean age 49.4 yr [range 29-74]) who underwent microsurgical vestibular
      schwannoma excision. INTERVENTIONS: Microsurgical excision. MAIN OUTCOME
      MEASURES: Linear fundal fluid size and tumor size calculated using volumetric
      analysis were measured on preoperative magnetic resonance imaging, and correlated
      to hearing status and postoperative facial nerve function. RESULTS: Mean fundal
      fluid size was 2.18 mm (range 0-7.32). Mean tumor volume was 5.58 cm (range,
      0.210-40.3 cm). Short- and long-term postoperative House-Brackmann scores were
      2.4 and 1.4, respectively. Fundal fluid size was associated with tumor volume (rs
      = 0.488, p = 0.003) but not preoperative hearing status (p = 0.333). The presence
      of fundal fluid and larger tumor volumes were statistically associated with
      poorer short-term and long-term postoperative facial nerve function (p < 0.05).
      CONCLUSIONS: Radiographic fundal fluid size is correlated to tumor volume.

PMID- 30239433
TI  - Causes of Persistent Positional Vertigo Following Posterior Semicircular Canal
      Occlusion for Benign Paroxysmal Positional Vertigo.
AB  - OBJECTIVE: To report causes of persistent recalcitrant positional vertigo (PRPV)
      after posterior semicircular canal occlusion (PSCO) for benign paroxysmal
      positional vertigo (BPPV). STUDY DESIGN: Retrospective chart review. SETTING:
      Single high-volume otology practice. PATIENTS: Patients diagnosed with BPPV from
      2007 to 2017. INTERVENTION: PSCO and follow-up care including diagnostic and
      particle repositioning maneuvers for recurrent BPPV. MAIN OUTCOME MEASURES: PRPV,
      defined as recalcitrant positional vertigo for any reason following PSCO.
      RESULTS: Twenty seven PSCO operations were performed in 26 patients. Twenty five
      patients (96.2%) had resolution of the Dix-Hallpike test in the operated ear.
      Eleven patients (42.3%) developed BPPV postoperatively, three (11.5%) in the
      operated ear and eight (30.8%) in the contralateral ear. Five of eight patients
      (62.5%) who developed contralateral BPPV had unilateral BPPV preoperatively.
      Eight patients (30.8%) developed BPPV at least twice after surgery or did not
      resolve, qualifying as PRPV, and all but one of these events occurred in the
      nonsurgical ear. No instances of cerebrospinal fluid leak, postoperative
      infection, facial palsy, clinically significant hearing loss, or death occurred.
      CONCLUSIONS: PSCO is a safe and effective option for recalcitrant BPPV. However,
      30.8% of patients, including patients with initially unilateral BPPV, had
      recalcitrant positional vertigo postoperatively, usually due to contralateral
      BPPV. Patients considering PSCO should be counseled regarding this risk to ensure
      realistic expectations.

PMID- 30239434
TI  - Noninvasive Registration Strategies and Advanced Image Guidance Technology for
      Submillimeter Surgical Navigation Accuracy in the Lateral Skull Base.
AB  - HYPOTHESIS: Combining novel registration strategies and advanced image guidance
      technology enable submillimeter accurate and noninvasive navigation for middle
      ear and lateral skull base surgery. BACKGROUND: Surgery in the internal auditory
      canal and the petrous apex present a cognitive and motoric challenge for the
      surgeon. To date, image guidance rarely assists these procedures, mainly due to
      the lack of navigation solutions providing submillimeter accuracy associated with
      low cost in terms of invasiveness, radiation, and time. METHODS: This study
      proposes an approach to clinically viable image guidance by using a combination
      of advanced image guidance technology and noninvasive registration strategies.
      Based on accuracy-optimized optical tracking hardware (accuracy: 0.05 +/- 0.025
      mm), 14 novel registration strategies were investigated. In human cadaveric
      temporal bone specimens n = 36 registration attempts per strategy were conducted.
      Target registration errors at 10 anatomical targets were measured. RESULTS: The
      most accurate registration strategies were identified as paired-point-matching
      using eight landmarks located in the external auditory canal and middle ear and
      surface matching using combined surfaces of the middle ear, the external auditory
      canal and the mastoid cortex yielding target registration errors of 0.51 +/- 0.28
      mm and 0.36 +/- 0.13 mm respectively. CONCLUSIONS: This study demonstrates
      submillimeter TREs achieved with noninvasive, anatomy-based registration
      strategies in combination with advanced image guidance technology. Clinically
      viable LSB and ME navigation is realized without additional invasiveness,
      radiation and time associated with artificial fiducials. The appropriate
      registration strategy can be chosen by the surgeon depending on the pathology and
      surgical approach.

PMID- 30239435
TI  - Development of a Mixed Reality Platform for Lateral Skull Base Anatomy.
AB  - OBJECTIVES: A mixed reality (MR) headset that enables three-dimensional (3D)
      visualization of interactive holograms anchored to specific points in physical
      space was developed for use with lateral skull base anatomy. The objectives of
      this study are to: 1) develop an augmented reality platform using the headset for
      visualization of temporal bone structures, and 2) measure the accuracy of the
      platform as an image guidance system. METHODS: A combination of semiautomatic and
      manual segmentation was used to generate 3D reconstructions of soft tissue and
      bony anatomy of cadaver heads and temporal bones from 2D computed tomography
      images. A Mixed-Reality platform was developed using C# programming to generate
      interactive 3D holograms that could be displayed in the HoloLens headset.
      Accuracy of visual surface registration was determined by target registration
      error between seven predefined points on a 3D holographic skull and 3D printed
      model. RESULTS: Interactive 3D holograms of soft tissue, bony anatomy, and
      internal ear structures of cadaveric models were generated and visualized in the
      MR headset. Software user interface was developed to allow for user control of
      the virtual images through gaze, voice, and gesture commands. Visual surface
      point matching registration was used to align and anchor holograms to physical
      objects. The average target registration error of our system was 5.76 mm +/-
      0.54. CONCLUSION: In this article, we demonstrate that an MR headset can be
      applied to display interactive 3D anatomic structures of the temporal bone that
      can be overlaid on physical models. This technology has the potential to be used
      as an image guidance tool during anatomic dissection and lateral skull base
      surgery.

PMID- 30239436
TI  - Temporal Bone CT Scan for Malleal Ligaments Assessment.
AB  - OBJECTIVE: To determine the feasibility of using temporal bone computed
      tomography (CT) scans to identify malleal ligaments and the prevalence of
      calcification in malleal ligaments. STUDY DESIGN: Retrospective case review. CT
      scans were blindly and retrospectively reviewed by two physicians (a radiologist
      and a nonradiologist). Scans differed by slice thickness, and included both
      conventional CT and cone beam CT (CBCT). SETTING: Ambulatory tertiary referral
      center. PATIENTS: One hundred fifty-one temporal bone CT scans, obtained between
      the years 2014 and 2017, were initially screened, which included 302 ears.
      Patients with previous tympanomastoid surgery or middle ear opacification were
      excluded, leaving 187 ears in the study. INTERVENTION: Diagnostic. MAIN OUTCOME
      MEASURE: Percentage of visible normal and calcified malleal ligaments. RESULTS:
      Scans with submillimeter slice thickness were more likely to demonstrate all
      three malleal ligaments than those with 1 ml and larger slices (83.7% versus
      50.0% for nonradiologist, p < 0.0001; 59.6 versus 34.8% for radiologist, p <
      0.0001). Calcification was seen in 11.8% of ears reviewed. The ability to detect
      malleal ligaments with cone beam CT was 86.2%, while the rate with conventional
      CT was 71.1%, a difference that persisted when controlling for slice thickness.
      Interobserver agreement for the detection of malleal ligaments was 65% with a
      Cohen's kappa coefficient of kappa = 0.27. CONCLUSION: Visualization of the
      malleal ligaments using CT scans is feasible in a majority of aerated ears.
      Detection of malleal ligaments improves with thinner slice thickness and cone
      beam technique. Low interobserver agreement suggests the importance of experience
      and a need for standardized review.

PMID- 30239437
TI  - Case Report of a New Coupler for Round Window Application of an Active Middle Ear
      Implant.
AB  - OBJECTIVES: To evaluate feasibility, surgical handling, audiological outcome, and
      coupling efficiency of a new coupler (custom-made device) for an active middle
      ear implant. PATIENT: Revision surgery after implantation of an active middle ear
      implant in a 66-year-old male patient with mixed hearing loss. INTERVENTION:
      Prosthetic hearing rehabilitation with a new coupler for round window
      application. MAIN OUTCOME AND RESULTS: The patient obtained good speech
      perception in quiet (word recognition scores 80%; Freiburg monosyllables) and
      noise (-3.3 dB SNR; Oldenburg Sentence Test). The effective gain with the
      Hannover coupler improved at frequencies > 0.5 kHz compared with the values
      reported for other round window (RW)-coupling modalities. CONCLUSION: The coupler
      provides a feasible option for the RW application of the middle ear implant
      actuator. The spring concept of the coupler needs to be improved to further
      standardize RW-coupling and improve coupling efficiency at low frequencies (0.5
      kHz).

PMID- 30239438
TI  - Variation in Tympanoplasty Cost in a Multihospital Network.
AB  - OBJECTIVES: Identify costs and operative times for tympanoplasty, and evaluate
      factors influencing cost and time variation. STUDY DESIGN: Retrospective cohort
      study. SETTING: Multihospital network. PATIENTS: Patients undergoing
      tympanoplasty from 2008 to 2016. Subjects with additional procedures were
      excluded. INTERVENTIONS: A multihospital network's standardized activity-based
      accounting system was used to determine costs and operative times of
      tympanoplasty. MAIN OUTCOME MEASURES: Correlation between variable factors and
      cost was calculated by Spearman correlation coefficients. Statistical comparisons
      of cost and time were made between surgeons and hospitals using an ANOVA test
      (Kruskal-Wallis) followed by Dunn's test to correct for multiple comparisons. All
      providers or hospitals with single cases were excluded for statistical
      comparison. RESULTS: The study cohort included 487 tympanoplasties performed by
      44 surgeons at 13 hospitals. Mean patient age was 18.2 +/- 17.4 years. Mean cut
      to-close time was 85.8 +/- 56.7 minutes. Mean total encounter cost was $3491 +/-
      $1,627. Substantial factors associated with total encounter cost were anesthesia
      cost (r = 0.8782; 95% CI 0.852-0.900, p < 0.001) and cut-to-close time (r =
      0.7543; 95% CI 0.707-0.7949, p < 0.001). The total itemized supply cost was less
      correlated with total encounter cost (r = 0.3176; 95% CI 0.2128-0.4151, p <
      0.001). Laser utilization (mean cost $541 +/- $343) and artificial graft material
      (mean cost $199 +/- $94) were the major supply costs. CONCLUSION: Significant
      variation in tympanoplasty costs exists among different surgeons and hospitals
      within a multihospital network. Reducing variation in costs while maintaining
      outcomes may improve healthcare value and eliminate waste.

PMID- 30239439
TI  - Microstructural Alterations in the Brains of Adults With Prelingual Sensorineural
      Hearing Loss: a Diffusion Kurtosis Imaging Study.
AB  - OBJECTIVE: To investigate the alterations in microstructural gray matter (GM) and
      white matter (WM) in adults with prelingual sensorineural hearing loss (SNHL)
      using diffusion kurtosis imaging (DKI) and explore whether the clinical data are
      associated with the whole brain structure changes in SNHL subjects. STUDY DESIGN:
      Prospective case study. SETTING: Tertiary class A teaching hospital. PATIENTS:
      Eighty adults with prelingual SNHL. INTERVENTION: Diagnostic. MAIN OUTCOME
      MEASURE: DKI-derived metrics, including mean kurtosis, radial kurtosis, axial
      kurtosis, fractional anisotropy, mean diffusivity, radial diffusivity, and axial
      diffusivity were applied to explore the differences in GM and WM between the
      groups across the whole brain with voxel-based analysis. RESULTS: Compared with
      the control group, adults with prelingual SNHL exhibited significantly decreased
      fractional anisotropy, mean kurtosis, radial kurtosis, and axial kurtosis in the
      bilateral superior temporal gyrus in both the GM and WM. No correlations were
      detected between these alterations and clinical data. CONCLUSIONS: These findings
      suggest that DKI can provide comprehensive characteristics to demonstrate
      reductions in the auditory cortical GM and hypomyelination of WM fibers in the
      auditory pathway caused by auditory deprivation early in life.

PMID- 30239440
TI  - Quality of Life Within the First 6 Months of Vestibular Schwannoma Diagnosis With
      Implications for Patient Counseling.
AB  - OBJECTIVE: To evaluate quality-of-life (QOL) in patients with sporadic vestibular
      schwannoma (VS) with particular focus on those recently diagnosed. STUDY DESIGN:
      Cross-sectional survey, Penn Acoustic Neuroma Quality of Life (PANQOL)
      instrument. SETTING: Acoustic Neuroma Association and a single tertiary referral
      center. PATIENTS: Patients with sporadic VS. MAIN OUTCOME MEASURES: Domain
      specific and total PANQOL scores comparing treatment modalities after adjusting
      for baseline covariates of interest. RESULTS: Among all 1,288 respondents there
      were 229 (18%) who were recently diagnosed and had not yet selected a treatment
      modality, 303 (24%) who were observed, 185 (14%) who underwent radiosurgery
      alone, 507 (39%) who underwent microsurgery alone, and 64 (5%) who underwent
      radiosurgery and microsurgery. After adjusting for covariates of interest, total
      PANQOL scores were highest for the observation cohort (65; 95% CI 62-68), lowest
      for patients treated with multimodality therapy (56; 51-61) and those recently
      diagnosed (58; 55-62), and intermediate for those who received microsurgery alone
      (60; 58-62) and radiosurgery alone (61; 57-64) (global comparison, p = 0.001).
      When comparing groups that received single-modality therapy, there were no
      statistically significant differences in total PANQOL scores at short (0-5 yr),
      intermediate (6-10 yr), or long-term (>=11 yr) follow-up after adjusting for
      baseline covariates (all, p > 0.05). CONCLUSION: A new diagnosis of VS frequently
      imparts significant anxiety on the patient and leads to a temporary reduction in
      QOL. Notably, anxiety domain QOL scores among patients with newly diagnosed VS
      are poorer than patients who have observed their tumor for 6 months or longer.
      When feasible, an initial period of observation may afford patients valuable time
      to reconcile with the new diagnosis, to learn more about treatment options, and
      to discover whether there is tumor growth. In turn, this valuable information can
      be used to inform sound decision-making regarding tumor management.

PMID- 30239441
TI  - Tinnitus Impacts on Speech and Non-speech Stimuli.
AB  - OBJECTIVE: To investigate how tinnitus affects the processing of speech and non
      speech stimuli at the subcortical level. STUDY DESIGN: Cross-sectional analytical
      study. SETTING: Academic, tertiary referral center. PATIENTS: Eighteen
      individuals with tinnitus and 20 controls without tinnitus matched based on their
      age and sex. All subjects had normal hearing sensitivity. INTERVENTION:
      Diagnostic. MAIN OUTCOME MEASURES: The effect of tinnitus on the parameters of
      auditory brainstem responses (ABR) to non-speech (click-ABR), and speech (sABR)
      stimuli was investigated. RESULTS: Latencies of click ABR in waves III, V, and
      Vn, as well as inter-peak latency (IPL) of I to V were significantly longer in
      individuals with tinnitus compared with the controls. Individuals with tinnitus
      demonstrated significantly longer latencies of all sABR waves than the control
      group. The tinnitus patients also exhibited a significant decrease in the slope
      of the V-A complex and reduced encoding of the first and higher formants. A
      significant difference was observed between the two groups in the spectral
      magnitudes, the first formant frequency range (F1) and a higher frequency region
      (HF). CONCLUSIONS: Our findings suggest that maladaptive neural plasticity
      resulting from tinnitus can be subcortically measured and affects timing
      processing of both speech and non-speech stimuli. The findings have been
      discussed based on models of maladaptive plasticity and the interference of
      tinnitus as an internal noise in synthesizing speech auditory stimuli.

PMID- 30239442
TI  - Compassion: A Critical Link in Extraordinary Care for Patients and Families.
AB  - Delivering clinical nursing expertise enveloped with compassion should be the
      expectation for care. Ensuring this level of excellence happens when a critically
      ill patient is transferred from one hospital to another is challenging yet
      imperative to the patient's and family's experience. The DAISY Foundation
      recognizes nurses who provide compassionate and extraordinary nursing care, as
      demonstrated in the stories of 2 nurses, from different organizations, who cared
      for the same patient and family and were honored with The DAISY Award.

PMID- 30239443
TI  - Cultural Competency Matters: Calling for a Deeper Understanding of Healthcare
      Disparities Among Nurse Leaders.
AB  - Healthcare disparities for racial and ethnic minority patients are a serious
      issue in the United States. Although socioeconomic factors are a key contributor
      to these disparities, there are many other influences, related to the patient,
      system, and provider. A key strategy to address provider-related factors is to
      assess the cultural competence of caregivers. Utilizing a survey and interviews
      of AONE members, this study explored the influences affecting the ability of
      nurse leaders to lead their teams in providing culturally competent care. The
      study found that nurse leaders need a deeper understanding of the presence of
      healthcare disparities for racial and ethnic minority patients, more formalized
      training, and increased opportunities to reflect on their own abilities and
      potential for bias. Cultural competence must be a strategic priority, providing
      resources for training, and by holding leaders accountable to improve the level
      of cultural competence of their teams.

PMID- 30239444
TI  - Employers as Consumers of Healthcare.
AB  - Amazon, Berkshire Hathaway, and JP Morgan Chase shocked the industry with its
      announcement to join forces to cut healthcare costs and improve healthcare
      services for its employees. This is just the latest of employer efforts to
      disrupt the industry by the creation of alternative healthcare delivery networks
      that demonstrate high-value, low-cost services as compared with what traditional
      provider systems have to offer. What factors are behind this industry disruption,
      and what are the key implications for nurse executives?

PMID- 30239445
TI  - Countering Unprofessional Behaviors Among Nurses in the Workplace.
AB  - OBJECTIVE: This study investigates the association of authentic leadership (AL)
      and perceived organizational support to workplace bullying among a sample of
      licensed practical nurses (LPNs). BACKGROUND: Workplace bullying is a serious
      problem in the workplace that harms nurses' physical and psychological well
      being. METHODS: A cross-sectional survey design was implemented. A simple random
      sample of 855 was drawn from a population of 4306 LPNs in a single US Midwestern
      state. A total of 168 usable questionnaires were returned (19.65% response rate).
      RESULTS: Forty-three percent of nurses experienced at least 2 negative behaviors
      on a weekly/daily basis; 12% self-identified as a victim. The moral component of
      AL was a major determinant of overall workplace bullying (beta = -.59), person
      related bullying (beta = -.70), and physical intimidation (beta = -.58).
      Perceived support was a major determinant of work-related bullying (beta = -.40).
      CONCLUSIONS: Organizational support initiatives and AL training for nurse leaders
      should be considered to reduce bullying.

PMID- 30239446
TI  - Evaluation of Outcomes From an Online Nurse Residency Program.
AB  - OBJECTIVE: This retrospective study examined the nurse outcomes from new-graduate
      nurse residents completing an online nurse residency program (NRP). BACKGROUND:
      Studies have shown that hospital-based NRPs help new graduates transition from
      beginners to competent nurses. However, NRPs can tax the resources of smaller
      institutions, making such a program unrealistic. Little is published exploring
      the efficacy of online programs for nursing residents. METHODS: Surveys assessing
      the impact of the online program were completed by residents in an online NRP at
      initiation, 6 months, and at completion. RESULTS: There were statistically
      significant improvements in organizational and prioritizing skills; confidence in
      communication with other healthcare providers, patients, and families; and
      improved leadership ability. The percentage of residents reporting negative
      safety practices and patient errors decreased over time. CONCLUSIONS: An NRP
      using online educational modules results in nurse outcomes comparable to those
      reported from traditional models.

PMID- 30239447
TI  - Evaluating the Clinical Practice Model's Strengths and Improvement Opportunities
      Using the Professional Practice Framework Assessment Survey: One Integrated
      Healthcare System's Experience.
AB  - OBJECTIVES: The aims of this study are (1) to describe the division,
      organizational strengths, and improvement opportunities of self-reported
      behaviors indicative of the multidimensional construct of professional practice
      and (2) to understand demographic characteristics that contributed to these
      strengths and improvement opportunities. BACKGROUND: Prior to implementing a
      system-wide interdisciplinary shared governance structure, ProHealth Care
      measured staff attitudes toward the multidimensional construct of professional
      practice as proposed within the Clinical Practice Model framework using the
      Professional Practice Framework Assessment Survey (PPFA-S). METHODS: Clinical and
      support staff were invited to share their views toward professional practice
      using the previously validated, reliable tool, the PPFA-S. RESULTS: Partnering
      relationships, scope of practice, and shared purpose were strengths. Strategies
      were initiated to strengthen networking councils, integrated competency, evidence
      based practice, transformative capacity, and clinical tools. CONCLUSIONS: The
      survey identified professional practice strengths and improvement opportunities
      across the organization as well as factors contributing to these strengths and
      opportunities. These findings were useful to help guide system integration.

PMID- 30239448
TI  - Predictors of Turnover Among Asian Foreign-Educated Nurses in Their 1st Year of
      US Employment.
AB  - OBJECTIVE: The aim of this study was to investigate factors affecting turnover of
      Asian foreign-educated nurses (FENs), which may lead to improvements in retention
      strategies. BACKGROUND: Asian FENs working in the United States have considerable
      rates of turnover. Little is known about which factors are related. METHODS: A
      cross-sectional design was used. A convenience sample (n = 201) of Asian FENs
      completed surveys by regular mail and through a website. Backward multivariable
      logistic regression was performed to identify factors associated with turnover in
      their 1st year of employment. RESULTS: Most participants were from the
      Philippines and Korea. Perceived quality of orientation predicted organizational
      level turnover and trended toward predicting unit-level turnover. CONCLUSIONS:
      Healthcare institutions may benefit from developing organizational programs for
      FENs that are sensitive to their unique needs, in the interest of reducing rapid
      or early turnover and accompanying negative effects on hospital finances and
      patient care.

PMID- 30239449
TI  - The Impact of Nurses' Uniforms on Nurse-Patient Interactions: Patients'
      Perspectives.
AB  - OBJECTIVES: The aim of this study was to explore patients' perceptions toward the
      nursing uniforms used in a hospital in Singapore and how different uniforms
      impact nurse-patient interactions. BACKGROUND: Nursing uniforms act as a form of
      nonverbal communication. However, implications of the increasing variety of
      nursing uniforms on patients' perceptions of nurses and nurse-patient
      interactions are unexplored. METHODS: An exploratory qualitative study design
      using semistructured interviews was adopted for the study. Twenty-one patients
      agreed to be interviewed. An audio recorder was used during data collection. The
      thematic analysis method was used for data analysis. RESULTS: Four major themes
      were identified: identity, subjectivity, suitability, and inconsequential.
      Nurses' uniform was regarded as a representation of identity. Suitability of the
      uniform for nurses was a main concern for patients. However, nurses' uniforms
      were inconsequential to nurse-patient interactions. CONCLUSION: Patients'
      perceptions of nurses' uniforms were highly subjective and have no substantial
      impact on nurse-patient interactions.

PMID- 30239450
TI  - Effects of an 8-Week In-Season Elastic Band Training Program on Explosive Muscle
      Performance, Change of Direction, and Repeated Changes of Direction in the Lower
      Limbs of Junior Male Handball Players.
AB  - Aloui, G, Hammami, M, Fathloun, M, Hermassi, S, Gaamouri, N, Shephard, RJ, and
      Chelly, MS. Effects of an 8-week in-season elastic band training program on
      explosive muscle performance, change of direction, and repeated changes of
      direction in the lower limbs of junior male handball players. J Strength Cond Res
      XX(X): 000-000, 2018-The aim of this study was to examine the effects of
      incorporating 8 weeks of biweekly lower-limb elastic band training (knee and hip
      extension) into the in-season regimen of junior handball players. Study
      participants (30 men, aged 18.7 +/- 0.8 years, body mass 81.1 +/- 15.4 kg, height
      1.82 +/- 0.06 m, body fat: 15.5 +/- 5.2%) were randomly assigned between control
      and experimental groups. Measures obtained before and after intervention included
      a cycle ergometer force-velocity test, force platform determinations of squat and
      countermovement jump characteristics, sprint times (5 and 30 m), repeated change
      of-direction (RCOD) and change-of-direction (T-half, COD) tests, 1 repetition
      maximum (RM) half back squat, and anthropometric estimates of limb muscle
      volumes. Small to trivial improvements of experimental subjects relative to
      control subjects included peak power (p < 0.001), 1RM strength measures (p <
      0.01), sprint times (p < 0.001 for 5 m; p < 0.05 for 30 m), COD (p < 0.01), and
      all RCOD parameters (p < 0.05) except the RCOD fatigue index. However, vertical
      jump parameters and limb volumes remained unchanged relative to controls. It may
      be concluded that adding biweekly elastic band training to a standard
      conditioning regimen yields small gains in measures that likely have an important
      influence on handball performance, particularly the ability to sprint, change
      direction, and make repeated changes of direction. Accordingly, such simple
      exercises can usefully be adopted as a component of handball training.

PMID- 30239451
TI  - Nordic Hamstring Strength of Highly Trained Youth Football Players and Its
      Relation to Sprint Performance.
AB  - Markovic, G, Sarabon, N, Boban, F, Zoric, I, Jelcic, M, Sos, K, and Scappaticci,
      M. Nordic hamstring strength of highly trained youth football players and its
      relation to sprint performance. J Strength Cond Res XX(X): 000-000, 2018-We aimed
      to characterize Nordic hamstring (NH) strength and bilateral NH strength
      asymmetry in highly trained youth footballers and to investigate the relationship
      between NH strength and sprint performance. Twenty-two adult and 133 highly
      trained youth footballers in the age groups U12-U18 participated in this study.
      Eccentric hamstring strength was assessed using the NH device. Youth footballers
      (n = 119) also performed 20-m sprint test. Age-related changes in absolute and
      relative NH strength, and bilateral NH strength asymmetry were analyzed using 1
      way analysis of variance. The linear relationship between relative NH strength
      and sprint performance was established using a Pearson correlation analysis.
      Significant age-related increases (F = 3.6-18.9; all p < 0.01) in NH strength
      were reported for all units except N.kg (F = 1.9; p = 0.08). The largest
      differences in absolute NH strength were seen between U15 and U16 groups.
      Bilateral NH strength asymmetry varied from 8 to 16% (F = 1.8; p = 0.09) across
      all age groups. A large correlation between NH strength and sprint performance
      was observed (r = -0.52; p < 0.01). Our results indicate that NH strength
      increases nonlinearly with players' age, with the highest values observed in U16
      group. Furthermore, bilateral NH strength asymmetry varied nonsignificantly
      between 8 and 16%. Finally, 27% of variance of sprint performance of youth
      footballers could be explained by relative NH strength. The reported NH strength
      data could be used as normative standards during testing and training of youth
      football players. Present results also suggest that coaches should pay close
      attention to eccentric hamstring function in youth footballers.

PMID- 30239452
TI  - Functional Basis of Asymmetrical Lower-Body Skeletal Morphology in Professional
      Australian Rules Footballers.
AB  - Hart, NH, Newton, RU, Weber, J, Spiteri, T, Rantalainen, T, Dobbin, M, Chivers,
      P, and Nimphius, S. Functional basis of asymmetrical lower-body skeletal
      morphology in elite Australian footballers. J Strength Cond Res XX(X): 000-000,
      2018-Bone strength is a product of its material and structural properties and is
      highly responsive to mechanical load. Given the measureable and adaptable
      features of bone, and thus relevance to medical screening, injury prevention, and
      injury management in athletes, this study describes the lower-body skeletal
      morphology of professional Australian rules footballers. Using a cross-sectional
      and quantitative study design, 54 professional Australian rules football players
      (n = 54; age: 22.4 +/- 3.8 years; height: 189.0 +/- 7.5 cm; body mass: 86.0 +/-
      8.6 kg; tibial length: 436.1 +/- 29.2 mm; and body fat: 9.9 +/- 1.7%) underwent
      tibiofibular peripheral quantitative computed tomography scans for the kicking
      and support limbs, and a whole-body dual-energy X-ray absorptiometry scans. The
      support leg was significantly stronger than the kicking leg (bone strength: p <=
      0.001; d = 0.47) with significantly greater bone mass (p < 0.001; d = 0.28),
      cross-sectional areas (p <= 0.002; d = 0.20), and greater cortex thickness (p =
      0.017; d = 0.20), owing to significantly greater periosteal apposition (p <=
      0.001; d = 0.29) and endocortical expansion (p = 0.019; d = 0.13), despite
      significantly lower cortical density (p = 0.002; d = -0.25). Disparate skeletal
      morphology between limbs highlights context-specific adaptive responses to
      mechanical loads experienced during game-based tasks. Practitioners should
      concomitantly measure material and structural properties of musculoskeletal
      tissue when examining fragility or resilience to better inform medical screening,
      monitoring, and injury risk stratification. Support leg axial loading highlights
      a potential avenue for interventions aiming to remediate or optimize bone cross
      sectional area.

PMID- 30239453
TI  - Divergent Blood Pressure Response After High-Intensity Interval Exercise: A
      Signal of Delayed Recovery?
AB  - Hunter, GR, Fisher, G, Bryan, DR, Borges, JH, and Carter, SJ. Divergent blood
      pressure response after high-intensity interval exercise: a signal of delayed
      recovery? J Strength Cond Res XX(X): 000-000, 2018-The objective of this
      commentary is to highlight potential factors influential to the adaptation of
      high-intensity exercise. Herein, we present a rationale supporting the contention
      that elevated systolic blood pressure, after a bout of high-intensity exercise,
      may be indicative of delayed/incomplete recovery. Relative to type I skeletal
      muscle fibers, the unique cellular/vascular characteristics of type II muscle
      fibers may necessitate longer recovery periods, especially when exposed to
      repeated high-intensity efforts (i.e., intervals). In addition to the noted race
      disparities in cardiometabolic disease risk, including higher mean blood
      pressures, African Americans may have a larger percentage of type II muscle
      fibers, thus possibly contributing to noted differences in recovery after high
      intensity exercise. Given that optimal recovery is needed to maximize
      physiological adaptation, high-intensity training programs should be individually
      tailored and consistent with recovery profile(s). In most instances, even among
      those susceptible, the risk to nonfunctional overreaching can be largely
      mitigated if sufficient recovery is integrated into training paradigms.

PMID- 30239454
TI  - Body Composition Variables by Sport and Sport-Position in Elite Collegiate
      Athletes.
AB  - Fields, JB, Merrigan, JJ, White, JB, and Jones, MT. Body composition variables by
      sport and sport-position in elite collegiate athletes. J Strength Cond Res XX(X):
      000-000, 2018-To assess body composition measures by sport and sport-position.
      Elite collegiate athletes participated (n = 475): men's and women's soccer (MSOC,
      n = 67; WSOC, n = 110); men's and women's swimming (MSWIM, n = 26; WSWIM, n =
      22); men's and women's track and field (MTF, n = 29; WTF, n = 24); women's
      lacrosse and volleyball (WLAX, n = 84; WVB, n = 73); and baseball (BASE, n = 40).
      One-way analysis of variances assessed differences across sport and sport
      position. Post hoc analysis was Tukey honestly significant difference (p <=
      0.05). For men, BASE and MSWIM had the highest body fat percentage (BF%) (BASE:
      16.3 +/- 5.2%; MSWIM: 14.2 +/- 3.5%). MSOC (11.5 +/- 5.3%, 0.13 +/- 0.72 kg) and
      MTF (9.8 +/- 5.1%, 0.11 +/- 0.08 kg) had the lowest BF% and fat mass (FM)-to-fat
      free mass (FFM) ratio (FM:FFM). Fat mass did not differ between MSOC (9.1 +/- 4.9
      kg), MTF (7.7 +/- 5.9 kg), and MSWIM (11.1 +/- 3.1 kg). Fat mass for MSOC and MTF
      was lower than BASE (14.1 +/- 5.2). For women, WVB displayed the highest BF%
      (25.4 +/- 5.1%), FM (18.5 +/- 5.2 kg), FFM (53.3 +/- 5.1 kg), and body mass (BM)
      (71.8 +/- 8.4 kg), but did not differ from WSWIM in BF%, FM, FFM, and BM. WTF had
      the lowest BF% (12.9 +/- 4.0%), FM (7.5 +/- 2.5 kg), BM (58.2 +/- 4.4 kg), and
      FM:FFM (0.15 +/- 0.05 kg). VB had the highest FFM (53.3 +/- 5.1 kg). Body
      composition differences were observed between sport-positions (p < 0.01). Body
      composition differed across sport and sport-position, which may be attributed to
      sport-specific physiological demands.

PMID- 30239455
TI  - Physical Fitness and Blood Glucose Influence Performance in IndyCar Racing.
AB  - Ferguson, DP and Myers, ND. Physical fitness and blood glucose influence
      performance in IndyCar racing. J Strength Cond Res XX(X): 000-000, 2018-Charlie
      Kimball (CK) is an elite-level IndyCar driver who has type 1 diabetes. Since CK
      became a full-time competitor, there has been exponential growth in the number of
      racing drivers competing with type 1 diabetes. Therefore, the purpose of this
      article is to present a case report of data collected on CK over 6 years, to
      better inform strength and conditioning coaches on how to prepare racing drivers
      with type 1 diabetes for competition. We hypothesized that the physical
      requirements to pilot the race car would include an elevated aerobic and
      glycolytic capacity and that blood glucose would influence key driving parameters
      (vertical gravitational force [Gz] tolerance and reaction time/response accuracy)
      related to success (finishing position). Physical fitness was evaluated with a
      V[Combining Dot Above]O2max test, dual-energy X-ray absorptiometry body
      composition analysis, Wingate power test, and a lower-body negative pressure test
      for vertical Gz tolerance. To test the role of fitness and blood glucose on
      driving performance, heart rate (HR), breath rate (BR), and skin temperature (ST)
      were evaluated during practice racing sessions using the Equivital Life Monitor.
      Blood glucose was monitored in 47 races using a continuous glucose monitor.
      Driving a race car resulted in increased HR, BR, and ST. The driver's body
      composition, skeletal muscle power output, and aerobic capacity values were in
      the 10th percentile of the average population. A blood glucose range of 100-168
      mg.dl was identified as optimal for driving performance for the case study
      participant because it improved reaction time/response accuracy and Gz tolerance.

PMID- 30239456
TI  - Effects of Two Different Tapering Protocols on Fitness and Physical Match
      Performance in Elite Junior Soccer Players.
AB  - Krespi, M, Sporis, G, and Trajkovic, N. Effects of two different tapering
      protocols on fitness and physical match performance in elite junior soccer
      players. J Strength Cond Res XX(X): 000-000, 2018-The purpose of this study was
      to determine the effects of 2 different tapering protocols on fitness and
      physical match performance in elite junior soccer players. One-hundred fifty
      eight elite junior soccer players (mean age: 17.1 +/- 0.79 years; mean height:
      177.9 +/- 6.64 cm; mean body mass: 71.3 +/- 7.96 kg; and mean body mass index:
      22.5 +/- 1.66 kg.m) were randomly assigned to 2 groups: an exponential (n = 79)
      and a linear tapering (n = 79) group. Training sessions were conducted 3 times
      per week for 8 weeks. After 4 weeks of training and 4 weeks of tapering,
      participants were assessed in terms of body composition, physical fitness, and
      distance covered within a match. Both groups showed similar changes for body
      composition. The exponential group showed better improvement than the linear
      group in the 5- and 30-m sprints, countermovement jump, and V[Combining Dot
      Above]O2max (p < 0.05). The exponential tapering group had larger changes (p <
      0.05) than the linear group in medium running (8-13 km.h) (6%; effect size = 0.26
      compared with 5.5%; effect size = 0.22) and sprinting (>18 km.h) (26%; effect
      size = 0.72 compared to 21.7%; effect size = 0.60). The results show that
      exponential tapering produced better effects on speed, power, and endurance
      abilities than the linear protocol. Our results confirmed the reports of others
      that suggest that volume is the optimal variable to manipulate while maintaining
      both the intensity and the frequency of sessions.

PMID- 30239457
TI  - Normative Data and Physical Determinants of Multiple Sprint Sets in Young Soccer
      Players Aged 11-18 Years: Effect of Maturity Status.
AB  - Selmi, MA, Sassi, RH, Yahmed, MH, Giannini, S, Perroni, F, and Elloumi, M.
      Normative data and physical determinants of multiple sprint sets in young soccer
      players aged 11-18 years: Effect of maturity status. J Strength Cond Res XX(X):
      000-000, 2018-The aims of the study were: (a) to establish normative data for
      repeated-sprint sets (RSS) test based on the maturity status (age at peak height
      velocity [PHV]) and (2) to investigate the relationship between anthropometrical
      variables (stature, sitting height, body mass, and body fat percentage), RSS (2 *
      5 * 20 m with 15-second recovery between sprints and 1-minute recovery between
      sets), and fitness tests {squat jump, countermovement jump, standing long jump,
      standing triple jump, 5-jump test, and 20-m shuttle run (multistage shuttle run
      test [MSRT])}. Young male soccer players (n = 262; age: 14.5 +/- 2.9 years) were
      evaluated and classified into 4 groups according to their maturity status: pre
      PHV, circum-PHV1, circum-PHV2, post-PHV. An analysis of variance and Bonferroni
      post hoc were used to determine maturity group differences (p <= 0.05), whereas
      Pearson's correlation was used between variables. Repeated-sprint sets' indices
      (sum of sprint times [SST] and best sprint time [BST]) were significantly
      different between the maturity groups. Significant correlations between SST with
      body mass (from -0.73 to -0.33) and MSRT (from -0.49 to -0.30) among each
      maturity group were found. With the different maturity groups, correlations
      between SST (s), BST (s), and vertical jump (cm) (r = -0.63 to -0.25 and r = 
      0.68 to -0.23) and horizontal jump (m) (r = -0.70 to -0.38 and r = -0.63 to 
      0.43) were observed. Repeated-sprint sets' values improve during maturation of
      young soccer players and the correlations between RSS and fitness tests vary
      through the maturity groups. This information could be useful for the coach to
      identify talent and to prescribe specific physical training to improve
      performance.

PMID- 30239458
TI  - Are We Overdiagnosing Pulmonary Embolism? "No".
AB  - Diagnosis of acute pulmonary embolism currently relies on computed tomography
      angiography which is acknowledged as a powerful, noninvasive tool. The concept of
      overdiagnosis is counterbalanced by a series of unanswered questions regarding
      the natural history of acute pulmonary embolism and the missing links between
      acute and chronic thromboembolic disease. For numerous reasons, it is less than
      certain that this concept will survive.

PMID- 30239459
TI  - Are We Overdiagnosing Pulmonary Embolism? Yes!: Paradigm Shift in Pulmonary
      Embolism.
AB  - Pulmonary embolism (PE) is a relatively common and potentially fatal pathology.
      Fear of missing the diagnosis is pervasive for physicians, including
      radiologists. However, as computed tomography pulmonary angiography technology
      and utilization have evolved over the years, we have gained an understanding that
      not all PEs are equal. As such, our interpretations of PE imaging studies must be
      enriched by this understanding and adapted to patient circumstances. Herein, we
      shine the light on overdiagnosis of PE, exploring the evidence, impact, costs,
      and consequences of overdiagnosis on the care of our patients.

PMID- 30239460
TI  - A Case of Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma With Lung
      Lesion.

PMID- 30239461
TI  - The Added Value of Computer-aided Detection of Small Pulmonary Nodules and Missed
      Lung Cancers.
AB  - Lung cancer at its earliest stage is typically manifested on computed tomography
      as a pulmonary nodule, which could be detected by low-dose multidetector computed
      tomography technology and the use of thinner collimation. Within the last 2
      decades, computer-aided detection (CAD) of pulmonary nodules has been developed
      to meet the increasing demand for lung cancer screening computed tomography with
      a larger set of images per scan. This review introduced the basic techniques and
      then summarized the up-to-date applications of CAD systems in clinical and
      research programs and in the low-dose lung cancer screening trials, especially in
      the detection of small pulmonary nodules and missed lung cancers. Many studies
      have already shown that the CAD systems could increase the sensitivity and reduce
      the false-positive rate in the diagnosis of pulmonary nodules, especially for the
      small and isolated nodules. Further improvements to the current CAD schemes are
      needed to detect nodules accurately, particularly for subsolid nodules.

PMID- 30239462
TI  - Diagnostic Overshadowing of Anxiety in Parkinson Disease: Psychosocial Factors
      and a Cognitive-Behavioral Model.
AB  - Anxiety in Parkinson disease (PD) is highly prevalent yet frequently
      underdiagnosed and undertreated, and historically overshadowed in research by a
      focus on depression. Recently, interest in anxiety has been building with the
      recognition of its significant impact on quality of life in PD. Anxiety is
      typically conceptualized as one of many "nonmotor" manifestations of neurologic
      change, with minimal consideration of potentially important psychosocial factors.
      This narrative review used a systematic search strategy to identify and
      synthesize the available evidence for psychosocial risk factors for anxiety.
      Thirty relevant articles were located and reviewed, and demographic,
      disease/pharmacologic, and psychosocial risk factors for anxiety in PD were
      identified. A prominent finding was that individuals with motor fluctuation
      appeared to be more vulnerable to anxiety. A cognitive-behavioral model of
      anxiety in PD is proposed and illustrated with a clinical example.

PMID- 30239463
TI  - Testing of Verbal Fluency in Egyptians: Cultural and Educational Challenges.
AB  - BACKGROUND: The importance of verbal fluency tasks as a cornerstone in cognitive
      assessment is now well acknowledged, as they provide fast, reliable tools for
      assessment of both verbal and executive function abilities. OBJECTIVES: To
      investigate the effect of age and education on verbal fluency and to develop a
      verbal fluency task that is culture-oriented and non-education-based to overcome
      the problem of illiteracy in Egypt. METHODS: Two groups of participants were
      recruited, a normal cognition control group (n=79) and a clinically demented
      group (n=32). Phonemic verbal fluency was tested by asking participants to
      generate as many words as they could think of starting with the Arabic letter
      Haa; category fluency was evaluated using four semantic categories (animals,
      fruits, vegetables, and names). RESULTS: Animal, vegetable, and name fluency
      tasks (unlike phonemic fluency and fruit) were not related to age and education,
      and they had better criterion validity (area under the receiver operating
      characteristic curve [AUC]=0.96, 0.91, and 0.92, respectively) than did letters
      and fruits (AUC=0.74 and 0.86, respectively). Our suggested cutoff points are 11
      for the animal fluency task (sensitivity=94%, specificity=93%), 11 for vegetables
      (sensitivity=84%, specificity=88%), and 18 for names (sensitivity=91%,
      specificity=82%). CONCLUSIONS: Animals, vegetables, and names are reliable and
      appropriate categories to be used for culture-oriented and non-education-based
      verbal fluency tests.

PMID- 30239464
TI  - Performance of Patients with Early Parkinson Disease on an Executive and Social
      Cognition Battery.
AB  - OBJECTIVE: To demonstrate the usefulness of incorporating the Executive and
      Social Cognition Battery (ESCB) to detect executive and social cognition
      deficits, which are otherwise not captured by more "classical" executive tests in
      early Parkinson disease (PD). BACKGROUND: PD is a neurodegenerative disorder that
      includes executive and social cognition deficits. While cognitive assessment in
      PD still relies on classical executive tasks to detect frontal deficits, these
      traditional tests often fail to uncover subtle, yet relevant, frontal impairment.
      METHODS: We evaluated 39 PD patients and 47 controls with a battery of classical
      executive tests and the ESCB. The ESCB includes a series of tasks that more
      closely resemble real-life activities and have been previously shown to be useful
      in detecting executive deficits in other neuropsychiatric disorders with frontal
      involvement. RESULTS: We observed that both batteries used in a complementary way
      yielded better results, as 15 of the 39 patients presented deficits only on some
      of the ESCB tests, but not on the classical battery, while 5 patients presented
      deficits only on some tests of the classical battery, but not on the ESCB.
      Fourteen patients presented deficits on some tests of either battery, and 5
      patients did not present deficits on any of the tests. CONCLUSIONS: We found
      that, used along with traditional neuropsychological tasks, the ESCB may be
      useful in providing a more comprehensive evaluation of frontal dysfunction among
      patients with PD, thus contributing to the early diagnosis of cognitive disorders
      in this patient population.

PMID- 30239465
TI  - Neuromodulation of Right Auditory Cortex Selectively Increases Activation in
      Speech-Related Brain Areas in Brainstem Auditory Agnosia.
AB  - Auditory agnosia is an inability to make sense of sound that cannot be explained
      by deficits in low-level hearing. In view of recent promising results in the area
      of neurorehabilitation of language disorders after stroke, we examined the effect
      of transcranial direct current stimulation (tDCS) in a young woman with general
      auditory agnosia caused by traumatic injury to the left inferior colliculus.
      Specifically, we studied activations to sound embedded in a block design using
      functional magnetic resonance imaging before and after application of anodal tDCS
      to the right auditory cortex. Before tDCS, auditory discrimination deficits were
      associated with abnormally reduced activations of the auditory cortex and
      bilateral unresponsiveness of the anterior superior temporal sulci and gyri. This
      session replicated a previous functional scan with the same paradigm a year
      before the current experiment. We then applied anodal tDCS over right auditory
      cortex for 20 min-utes and immediately re-scanned the patient. We found increased
      activation of bilateral auditory cortices and, for speech sounds, selectively
      increased activation in Broca's and Wernicke's areas. Future research might
      consider the long-term behavioral effects after neurostimulation in auditory
      agnosia and its potential use in the neurorehabilitation of more general auditory
      disorders.

PMID- 30239466
TI  - The Telephone Interview for Cognitive Status.

PMID- 30239468
TI  - The Telephone Interview for Cognitive Status.

PMID- 30239467
TI  - The Telephone Interview for Cognitive Status.

PMID- 30239469
TI  - The Telephone Interview for Cognitive Status.

PMID- 30239470
TI  - Early Diagnosis of Frontotemporal Dementia.

PMID- 30239471
TI  - Positional Ocular Flutter Associated With Middle Cerebellar Peduncle
      Demyelination.

PMID- 30239473
TI  - Predictors of 30-day Postdischarge Readmission to a Multistate National Sample of
      State Psychiatric Hospitals.
AB  - BACKGROUND: Early discharge from psychiatric inpatient care may pose challenges
      for the patient's recovery and may incite a rapid return to the hospital. This
      study identified demographic, clinical, and the continuing of care
      characteristics associated with rapid readmission into a sample of psychiatric
      inpatient hospitals. METHODS: Cross-sectional analysis of 60,254 discharges from
      state psychiatric hospitals. Logistic regression explored the relationship
      between predictors of rapid readmission. RESULTS: Eight percent of discharges
      were readmitted to the same hospital within 30 days after discharge. Factors
      significantly related with rapid readmission included white (odds ratio, 1.23;
      95% confidence interval, 1.13-1.34), non-Hispanic (1.48, 1.26-1.73), not married
      (1.53, 1.32-1.76), voluntarily admitted (1.18, 1.05-1.33), with length of stay
      (LOS) <= 7 days (3.52, 3.04-4.08), or LOS 8-31 days (3.20, 2.79-3.66), or LOS 32
      92 days (1.91, 1.65-2.22), with a schizophrenia or other psychotic disorders
      (1.69, 1.46-1.96) or personality disorder (1.76, 1.50-2.06), referred to a
      setting different from the outpatient (1.27, 1.16-1.40), or with a living
      arrangement different from private residence (1.54, 1.40-1.68). CONCLUSIONS:
      Disparities in rapid readmission rates exist among state psychiatric hospitals. A
      national overview of the individuals with mental illness at risk of being
      prematurely discharged may suggests insights into quality initiatives aimed at
      reducing rapid readmissions into psychiatric inpatient care.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.

PMID- 30239472
TI  - Comparison between technetium-99m methoxyisobutylisonitrile scintigraphy and
      ultrasound in the diagnosis of parathyroid adenoma and parathyroid hyperplasia.
AB  - OBJECTIVE: The aim of this study was to evaluate the value of technetium-99m
      methoxyisobutylisonitrile (Tc-MIBI) imaging and ultrasound in preoperative
      localization of parathyroid adenoma (PA) and parathyroid hyperplasia (PH).
      PARTICIPANTS AND METHODS: A retrospective study of Tc-MIBI double-phase
      scintigraphy (DPS) was performed in 187 hyperparathyroidism cases with
      pathologically diagnosed PA or PH. Of these patients, 167 cases underwent
      ultrasound, and 146 cases underwent Tc-MIBI single-photon emission computed
      tomography/computed tomography (SPECT/CT). The sensitivity and diagnostic
      accuracy of ultrasound, Tc-MIBI DPS, and SPECT/CT were compared between PA and
      PH. Differences in Tc-MIBI DPS, serum parathyroid hormone (PTH), serum calcium
      and phosphorus, as well as the weight and longest diameter of lesion between PA
      and PH were also compared. RESULTS: As per patient-based analysis, the
      sensitivity of ultrasound, Tc-MIBI DPS, and SPECT/CT was 90.70% (39/43), 95.56%
      (43/45), and 100.00% (30/30), respectively, for PA, and 93.55% (116/124), 90.85%
      (129/142), and 93.10% (108/116), respectively, for PH. There were no significant
      differences in sensitivity of these three imaging methods between PA and PH.
      However, per lesion-based analysis, the accuracy of ultrasound, Tc-MIBI DPS, and
      SPECT/CT in detecting PA was 78.43% (40/51), 86.79% (46/53) and 96.88% (31/32),
      respectively, and the accuracy of Tc-MIBI DPS was higher than that of ultrasound
      (chi=6.507, P=0.011), and for PH, it was 49.69% (160/322), 40.71% (171/420), and
      43.80% (152/347), respectively. The accuracy of ultrasound was higher than that
      of Tc-MIBI DPS (chi=5.940, P=0.015). The accuracy of a combination of all three
      examinations of ultrasound+Tc-MIBI DPS, ultrasound+Tc-MIBI SPECT/CT, Tc-MIBI
      DPS+SPECT/CT, and ultrasound+Tc-MIBI DPS+Tc-MIBI SPECT/CT was 51.51% (154/299),
      53.85% (161/299), 50.17% (150/299), and 54.18% (162/299), respectively, which was
      higher than that of ultrasound (chi=5.273, P=0.022; chi=8.226, P=0.004;
      chi=3.880, P=0.049; chi=8.702, P=0.003, respectively). Serum levels of PTH and
      phosphorus were lower in patients with PA than in patients with PH (P<0.001), and
      serum calcium level, the weight, and the longest diameter of lesion and early
      uptake rate of Tc-MIBI DPS were higher in patients with PA than in patients with
      PH (P<0.01). Serum PTH level is often less than 1000 pg/ml in PA, but usually
      more than 1000 pg/ml in PH. CONCLUSION: Ultrasound, Tc-MIBI DPS, and SPECT/CT all
      have a higher value in the diagnosis of PA than PH. Tc-MIBI SPECT/CT should be
      optimal for detecting PA, and early SPECT/CT scan might be better than delayed
      scan. Compared with Tc-MIBI DPS and SPECT/CT, ultrasound has a slight advantage
      in localization of PH lesions. The combination of ultrasound and Tc-MIBI DPS or
      SPECT/CT imaging could improve the accuracy in localization of PH lesions and
      should be considered as the first-line method for detecting PH.

PMID- 30239474
TI  - Delayed Seroreversion in HIV-Exposed Uninfected Infants.
AB  - BACKGROUND: Recent studies report delayed anti-HIV antibody clearance
      (seroreversion) among HIV-exposed uninfected infants that may affect diagnostic
      practices. We evaluated the age-specific seroreversion rates in Thailand.
      METHODS: The medical records of HIV-exposed uninfected infants born in January
      2000-December 2014 were reviewed. Anti-HIV seroreversion rates at 12, 18 and 24
      months were analyzed in three periods according to the Thai National Guidelines
      of prevention of mother-to-child transmission of HIV; zidovudine with or without
      single dose nevirapine to all women (2000-2006), adding lamivudine plus
      nevirapine to zidovudine in women with CD4 count <200 cells/mm (2007-2009),
      zidovudine plus lamivudine plus boosted lopinavir to all women (2010-2014). In
      2013 the serologic test kit was changed from third (3G) to fourth generation
      assay (4G). All the infants were formula-fed. RESULTS: Among 736 infants, the
      overall seroreversion rates at 12, 18, and 24 months of age were 59.38%, 94.57%,
      and 100%, respectively. The seroreversion rates at 12 months of age declined from
      68% in 2000-2006 and 65.9% in 2007-2009, to 42.9% in 2010-2014 (p=0.001).
      Seroreversion rates at 18 months of age were more than 96.5% before 2013 and
      decreased to 79.1% in 2013-2014 (p=0.001) with use of 4G. Multivariate analysis
      identified antepartum protease inhibitors treatment and the use of 4G testing as
      independent factors associated with delayed seroreversion. CONCLUSION: Anti-HIV
      seroreversion delay in HIV-exposed uninfected infants was associated with use of
      protease inhibitors and 4G HIV testing, complicating the interpretation to
      exclude perinatal HIV infection.

PMID- 30239475
TI  - Diarrhea-Associated Mortality in Children Less Than 5 Years of Age in the United
      States, 2005-2016.
AB  - Diarrheal disease morbidity decreased after the 2006 US introduction of rotavirus
      vaccine. We calculated diarrheal death rates for children who were <5 years of
      age during 2005-2016. Death rates declined from 2.3/100,000 (2005-2006) to
      1.7/100,000 (2014-2016). Declines were seen among 1-23 month olds, white and
      black children. Further exploration of the role of rotavirus vaccine in
      decreasing deaths among children is warranted.

PMID- 30239476
TI  - Staphylococcus aureus Bacteremia in Children: Antibiotic Resistance and
      Mortality.
AB  - BACKGROUND: Staphylococcus aureus (SA) is a major cause of bacteremia in
      children. Methicillin-resistant SA (MRSA) is considered a public health threat;
      however, the differences in the prognosis of children with methicillin
      susceptible SA (MSSA) vs. MRSA bacteremia are not well defined. METHODS: Data
      from all SA bacteremia events in children (0-16 years) from 2002 to 2016 in a
      single Israeli tertiary center were collected. Positive cultures within 48 hours
      of hospitalization were considered community associated (CA). Those obtained
      afterwards or from children hospitalized within the previous year were considered
      health-care associated (HA). RESULTS: We recorded 427 events, 284 (66%) were HA,
      64 (15%) were MRSA and 9 (2%) were CA-MRSA. There was no increase in MRSA during
      the study period. In-hospital, 30-day and one-year mortality were 3% (12 cases),
      3.5% (16 cases) and 12% (50 cases), respectively. A multivariable analysis
      controlling for demographics, admitting department and prior morbidity showed an
      increased one-year mortality in children with HA bacteremia (HR 4.1; 95% CI 1.3
      12) and prior chronic disease (HR 3.4; 95% CI 1.2 to 9.0). MRSA was not
      independently associated with increased one-year mortality compared to MSSA: HR
      (95%CI) 1.4 (0.6 to 3.1). CONCLUSIONS: Short-term pediatric mortality after SA
      bacteremia is low. HA-SA bacteremia has an increased long-term risk for
      mortality, particularly in children with chronic diseases. Our data suggest
      mortality was not increased for MRSA compared with MSSA bacteremia. The very low
      rate of CA-MRSA bacteremia justifies the current practice not to include
      glycopeptides in the empiric treatment of CA bacteremia in Israel.

PMID- 30239477
TI  - Gait Analysis After Intertrochanteric Hip Fracture: Does Shortening Result in
      Gait Impairment?
AB  - OBJECTIVE: To determine the association between fracture collapse with altered
      gait after intertrochanteric (IT) fracture using the trochanteric fixation nail
      (TFN) and helical blade. DESIGN: Prospective cohort study. SETTING: Academic
      Level I trauma center. PATIENTS: Seventy-two patients with IT hip fractures
      (OTA/AO 31) treated between 2012 and 2016. The average age was 79.7 years (range,
      51-94 years); there were 59 women and 13 men. INTERVENTION: All patients were
      treated with cephalomedullary nailing using the TFN (DePuy-Synthes, West Chester,
      PA) with a helical blade. MAIN OUTCOME MEASURES: At follow-up appointments,
      temporospatial gait parameters were measured and recorded. Radiographs were
      analyzed at the time of surgery and at each follow-up visit. Amount of
      radiographic femoral neck shortening was measured radiographically. Patients
      completed the Harris Hip Score, visual analog scale for pain, Short Form-36
      Physical Component Score, and Short Form-36 Mental Component Score. RESULTS: The
      mean length of follow-up between the surgery and the gait analysis was 8.6 months
      (+/-0.7 months). The mean amount of shortening was 4.7 mm (+/-0.6 mm). Out of the
      72 patients analyzed, there were 15 patients (20.8%) who shortened more than 8
      mm, 7 patients (9.7%) who shortened 10 mm or more, and 2 patients (2.8%) who
      shortened more than 20 mm. Mean shortening was 3.0 mm for stable OTA/AO 31-A1
      fractures, whereas the unstable patterns (OTA/AO 31-A2, 31-A3) demonstrated a
      mean shortening of 5.9 mm (P = 0.02). There was significant correlation between
      increased shortening and decreased cadence (P = 0.008), increased double support
      time (P < 0.001), decreased step length (P = 0.001), and increased single support
      asymmetry (P = 0.04) during gait analysis. The threshold of 8 mm of shortening
      predicted decreased cadence (P = 0.008), increased double support time (P <
      0.001), and decreased step length (P = 0.006). Analysis of patient-reported
      outcome scores, including the Harris Hip Score, visual analog scale, SF-36
      Physical Component Score, and SF-36 Mental Component Score, revealed no
      significant association with shortening. CONCLUSIONS: Results from this study
      indicate that shortening after cephallomedullary nailing of IT hip fractures
      using the TFN with a helical blade is associated with altered gait, specifically
      decreased cadence, increased double support time, decreased step length, and
      increased single support time asymmetry. LEVEL OF EVIDENCE: Prognostic Level II.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 30239478
TI  - Gender differences in cardiology: is it time for new guidelines?
AB  - : Despite cardiovascular disease (CVD) now being the leading cause of morbidity
      and mortality in women worldwide, this problem is still dramatically
      underestimated. The disparities in diagnosis, treatment, and prognosis between
      men and women are rooted in basic biological differences, as well as in the
      complex interactions of cultural and socioeconomic problems. This is why an up-to
      date and gender-based revision of current guidelines is highly desirable.

PMID- 30239480
TI  - Incivility in the Emergency Department: Implications for Nurse Leaders.

PMID- 30239479
TI  - Characteristics of Nurse Directors That Contribute to Registered Nurse
      Satisfaction.

PMID- 30239481
TI  - The Impact of Nursing Leader's Behavioral Integrity and Intragroup Relationship
      Conflict on Staff Nurses' Intention to Remain.

PMID- 30239483
TI  - Decreasing Work Place Incivility.

PMID- 30239482
TI  - Exploring Distress Caused by Blame for a Negative Patient Outcome.

PMID- 30239485
TI  - The Emotional Well-Being of Nurses and Nurse Leaders in Crisis.

PMID- 30239486
TI  - The Use of Bioimpedance in Pediatric Health, Nutrition, and Disease.

PMID- 30239484
TI  - Measuring Nurse Leaders' and Direct Care Nurses' Perceptions of a Healthy Work
      Environment in Acute Care Settings, Part 3: Healthy Work Environment Scales for
      Nurse Leaders and Direct Care Nurses.

PMID- 30239488
TI  - Pancreas With Multiple Cysts.

PMID- 30239487
TI  - Adenomyomatosis of the Gallbladder With Pancreaticobiliary Maljunction in a
      Child.

PMID- 30239489
TI  - Response to the Letter on "Efficacy of Reslizumab for EoE" by Dr Fuchs.

PMID- 30239490
TI  - No Screen and Treat in Children for Helicobacter pylori Infection.

PMID- 30239491
TI  - Effects of Napping on Alertness, Cognitive, and Physical Outcomes of Karate
      Athletes.
AB  - PURPOSE: It has been suggested that napping is the best recovery strategy for
      athletes. However, researches on the impacts of napping on athletic performances
      are scarce. The aim of this study was to determine the effects of a 30-minute nap
      following a partial sleep deprivation, or a normal night condition, on alertness,
      fatigue, and cognitive and physical outcomes. METHODS: Thirteen national-level
      male karate athletes were randomized to experience nap and no-nap conditions,
      after either a reference or a partial sleep deprivation night. The nap lasted 30
      minutes at 13:00. The post-nap testing session started at 14:00 by quantifying
      subjective alertness and fatigue. Cognitive and physical performances were
      respectively measured before and after the Karate Specific Test (KST) by Simple
      Reaction Time (SRT) test, Lower Reaction Test (LRT), Mental Rotation Test (MRT),
      Squat Jump (SJ) and Counter Movement Jump (CMJ) tests. RESULTS: After a reference
      night, the nap improved alertness and cognitive outcomes (SRT, LRT, and MRT). No
      effects on subjective fatigue and physical performances were found. After a
      partial-sleep deprivation, the nap restored subjective alertness and the
      decrement in performances caused by sleep loss in most of the tests (MRT, LRT,
      and KST), but no effects were observed in subjective fatigue and CMJ. After the
      fatigue induced by KST, there was an ergogenic effect of the nap on the physical
      performances (CMJ, and SJ), and a partial psychogenic effect on the cognitive
      performances (LRT). CONCLUSION: A 30-minute nap enhances cognitive outcomes. It
      is also an effective strategy to overcome the cognitive and physical
      deteriorations in performances caused either by sleep loss or by fatigue induced
      by exhaustive trainings in the afternoon.

PMID- 30239492
TI  - Exercise Increases MAIT Cell Cytokine Expression but not Activation or Homing
      Markers.
AB  - : Mucosal associated invariant T (MAIT) have properties of both the innate and
      adaptive immune systems but are an understudied population within exercise
      immunology. These lymphocytes aggregate at the mucous membranes, but it is
      unknown if submaximal exercise alters their circulating numbers or function.
      PURPOSE: To determine the MAIT cell response to submaximal exercise on activation
      and homing marker expression and stimulated cytokine production. METHODS: Twenty
      healthy, young, recreationally active males cycled for 40 min at 86% of VT
      following an overnight fast. Peripheral blood mononuclear cells were isolated and
      labelled to identify specific MAIT cell populations using flow cytometry.
      Cytokine production following stimulation was also determined. RESULTS: MAIT
      cells were 2.9% of T-cells and increased to 3.9% after exercise and with recovery
      whereas cell numbers significantly increased by 91.5% following exercise before
      returning to resting levels. Chemokine and activation marker absolute cell number
      significantly increased while expression levels remained constant but the high
      levels of CCR5 may help direct MAIT cells to sites of inflammation. Following
      stimulation, TNFalpha expression significantly increased after exercise before
      returning to baseline with a similar trend for IFNgamma. CONCLUSIONS: MAIT cell
      numbers undergo a partial biphasic response following submaximal exercise and
      appear to be preferentially mobilized within T-cells; however, the magnitude of
      the submaximal response was attenuated relative to maximal exercise. Stimulated
      MAIT cells increase TNFalpha expression, indicating greater responsiveness to
      pathogens following acute exercise.

PMID- 30239493
TI  - Health-related Outcomes following a Youth Sport-related Knee Injury.
AB  - PURPOSE: Active youth are vulnerable to knee injury and subsequent
      osteoarthritis. Improved understanding of the association between health-related
      outcomes and history of joint injury could inform osteoarthritis prevention
      strategies. The purpose of this historical cohort study is to examine the
      association between youth sport-related knee injury and various clinical,
      physiological, behavioral and functional health-related outcomes, 3-10 years post
      injury. METHODS: Participants included 100 individuals who experienced a youth
      sport-related knee injury 3-10 years earlier and 100 age, sex and sport-matched
      uninjured controls. Outcomes include; Knee injury and Osteoarthritis Outcome
      Score (KOOS), Intermittent and Constant Osteoarthritis Pain Score, body mass
      index (BMI), fat mass index (FMI), weekly physical activity, estimated aerobic
      capacity, hip and knee muscle strength, and dynamic balance. Baseline
      characteristics were described. Multivariable regression models (95%CI) were used
      to evaluate the association between injury history and each outcome, considering
      the influence of sex and time-since-injury. RESULTS: Participant median age was
      22 years (range 15-26) and 55% were female. The injured group demonstrated poorer
      KOOS sub-scale scores, more total and intermittent pain, higher BMI (1.8kg/m;
      95%CI 0.9,2.6), higher FMI (1.1kg/m; 95%CI 0.5,1.6), weaker knee extensor (-0.18
      NM/kg; 95%CI -0.33,-0.02) and flexor (-0.21 Nm/kg; 95%CI -0.30,-0.11) muscles,
      and poorer balance than controls. In the previously injured group, female sex was
      associated with poorer KOOS quality-of-life scores, knee flexor strength and
      greater FMI, while longer time-since-injury was associated with poorer KOOS
      symptoms scores, knee extensor strength and balance outcomes. CONCLUSION: Youth
      that suffer a sport-related knee injury demonstrate on average more negative
      health-related outcomes consistent with future osteoarthritis compared to
      uninjured matched controls 3-10 years following injury. These negative outcomes
      differ by sex and time-since-injury.

PMID- 30239494
TI  - Baseline Concussion Clinical Measures Are Related to Sensory Organization and
      Balance.
AB  - PURPOSE: To examine relationships among baseline demographics, symptom severity,
      computerized neurocognitive outcomes, and balance performance in collegiate
      athletes. METHODS: Collegiate varsity athletes (N=207, age=19.3 +/- 1.0 years)
      participating in an ongoing clinical research program who completed concussion
      baseline assessments including a demographic questionnaire, graded symptom
      checklist, neurocognitive assessment, and the Sensory Organization Test (SOT)
      were included in this study. The SOT composite equilibrium score (COMP) and three
      sensory ratio scores-vestibular (VEST), visual (VIS), and somatosensory (SOM)
      were used to describe athletes' overall sensory organization and ability to
      utilize input from each sensory system to maintain balance. Separate stepwise
      multiple linear regression models were performed for each SOT outcome. Total
      symptom severity level and CNS Vital Signs domain scores served as predictor
      variables. RESULTS: Stepwise regression models for COMP (R = 0.18, F4,201 =
      11.29, P <0.001), VEST (R = 0.14, F4,201 = 8.16, P<0.001), and VIS (R = 0.10,
      F4,201 = 5.52, P <0.001) were all significant. Faster reaction times and higher
      executive function scores were associated with higher COMP and VEST scores in
      separate models. Those with faster reaction times also had significantly higher
      VIS scores. CONCLUSION: Reaction time and executive function demonstrated
      significant relationships with SOT balance performance. These cognitive processes
      may influence athletes' ability to organize and process higher order information
      and generate appropriate responses to changes in their environment, with respect
      to balance and injury risk. Future investigations should consider these
      relationships following injury and clinicians should be mindful of this
      relationship when considering concussion management strategies.

PMID- 30239495
TI  - Validation of the Six-Minute Walk Test for Predicting Peak VO2 in Cancer
      Survivors.
AB  - PURPOSE: To assess the quality of the relationship between VO2peak estimated from
      patient outcomes on the 6-minute walk test (6-MWT) and the VO2peak calculated
      from patient outcomes on the University of Northern Colorado Cancer
      Rehabilitation Institute (UNCCRI) treadmill protocol. METHODS: Cancer survivors
      (N = 187) completed the UNCCRI treadmill protocol and a 6MWT one week apart in
      randomized order to obtain VO2peak. Values from the UNCCRI treadmill protocol
      were compared against four common 6MWT VO2peak prediction equations. RESULTS: All
      four 6MWT prediction equations significantly (p < 0.001) underestimated VO2peak
      with predicted values ranging from 8.0 +/- 4.1 to 18.6 +/- 3.1 mL/kg/min, while
      the UNCCRI treadmill protocol yielded a significantly higher value of 23.9 +/-
      7.6 mL/kg/min. A positive strong correlation occurred between estimated VO2peak
      derived from the UNCCRI treadmill protocol and only one of the VO2peak values
      derived from the 6MWT prediction equations (r = 0.81), and all four equations
      consistently underpredicted VO2peak. CONCLUSION: These findings suggest that the
      6MWT is not a valid test for predicting VO2peak in the cancer population due to
      its consistent underestimation of VO2peak regardless of the prediction equation.
      Obtaining an accurate and valid VO2peak value is necessary in order to correctly
      prescribe an individualized exercise rehabilitation regimen for cancer survivors.
      It is recommended that clinicians avoid the 6MWT and instead implement treadmill
      testing to volitional fatigue to quantify VO2peak in cancer survivors.

PMID- 30239496
TI  - MBN 2016 Aesthetic Breast Meeting BIA-ALCL Consensus Conference Report.

PMID- 30239497
TI  - Identifying Predictors of Time to Soft-Tissue Reconstruction following Open Tibia
      Fractures.
AB  - BACKGROUND: Controversy remains regarding the optimal timing of soft-tissue
      coverage following severe lower extremity trauma. This study identifies
      nationwide practice patterns and factors associated with discrepancies in time to
      first flap surgery following open tibia fractures. METHODS: A retrospective
      analysis was performed on the National Trauma Databank from 2008 to 2015 to
      identify patients who presented with an open tibia fracture and underwent
      subsequent flap reconstruction. A least absolute shrinkage and selection operator
      algorithm was performed, revealing those factors most significantly associated
      with differences in time to flap surgery from hospitalization. RESULTS: A total
      of 3297 patients were included in the analysis. Mean +/- SD and median times to
      first flap surgery were 230.1 +/- 246.7 hours and 169.1 hours, respectively.
      Older age, nonwhite race, treatment in the South, and non-private insurance
      status were all independently associated with an increased time to flap surgery.
      In addition, more surgical debridements; a higher Injury Severity Score and/or
      Abbreviated Injury Scale score; and a nerve, vascular, and/or crush injury were
      independent predictors of an increased time to flap surgery. CONCLUSIONS: Most
      patients who present with open tibia fractures requiring soft-tissue coverage
      undergo flap reconstruction after the historical 72-hour window. Specific
      sociodemographic and clinical factors were independently predictive of an
      increased time to flap surgery. These findings suggest that not all patients in
      the United States are receiving the same level of care in lower extremity trauma
      reconstruction, emphasizing the need to develop more explicit national standards.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 30239498
TI  - Optimal Sites for Supermicrosurgical Lymphaticovenular Anastomosis: An Analysis
      of Lymphatic Vessel Detection Rates on 840 Surgical Fields in Lower Extremity
      Lymphedema Patients.
AB  - BACKGROUND: Supermicrosurgical lymphaticovenular anastomosis is becoming a useful
      treatment option for progressive lower extremity lymphedema because of its
      minimal invasiveness. Finding a lymphatic vessel is a minimum requirement for
      lymphaticovenular anastomosis surgery, but no study has reported comprehensive
      analysis on factors associated with lymphatic vessel detection. METHODS: One
      hundred thirty-four female secondary lower extremity lymphedema patients who
      underwent indocyanine green lymphography and lymphaticovenular anastomosis
      without a history of lymphedema surgery were included. Medical charts were
      reviewed to obtain clinical, indocyanine green lymphographic, and intraoperative
      findings. Lymphatic vessel detection was defined as positive when one or more
      lymphatic vessels were found in a surgical field of lymphaticovenular
      anastomosis. Logistic regression analysis was used to identify independent
      factors associated with lymphatic vessel detection. RESULTS: Patient age ranged
      from 36 to 81 years, duration of edema ranged from 3 to 324 months, and body mass
      index ranged from 16.2 to 33.3 kg/m. Forty-eight patients (35.8 percent) had a
      history of radiation therapy, and 76 patients (56.7 percent) had a history of
      cellulitis. Lymphaticovenular anastomoses were performed in 840 surgical fields,
      among which lymphatic vessel detection was positive in 807 fields; the overall
      lymphatic vessel detection rate was 96.1 percent. Multivariate analysis revealed
      inverse associations in higher body mass index (OR, 0.323; p = 0.008) and the S
      region/D-region on indocyanine green lymphography compared with the L-region (OR,
      1.049 * 10/1.724 * 10; p < 0.001/p < 0.001). CONCLUSIONS: Independent factors
      associated with lymphatic vessel detection were clarified. Lower body mass index
      and L-region on indocyanine green lymphography are favorable conditions for
      finding lymphatic vessels in lower extremity lymphedema patients. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 30239499
TI  - Toward the Assessment of Core Procedural Competencies among Canadian Plastic
      Surgery Residents.
AB  - BACKGROUND: Plastic surgery residency training programs are working toward
      integrating competency-based education into program curriculum and training, a
      key component of which involves establishing core procedural competencies. This
      study aims to determine the exposure of graduating Canadian plastic surgery
      residents to established core procedural competencies. METHODS: A retrospective
      review of case log procedure data using three databases (T-Res, POWER, and New
      Innovations) from graduating residents at all 10 Canadian English-speaking
      plastic surgery training programs between 2004 and 2014 was completed. Case logs
      were coded according to 177 core procedural competencies identified as "core" by
      the Delphi method among an expert panel of Canadian plastic surgeons. RESULTS: A
      total of 59,405 procedures were logged by 55 graduating residents across Canada
      between 2004 and 2014 (average, 1080 +/- 352 procedures per resident). Of 13
      plastic surgery domains, 44 percent of all procedures were within either hand,
      upper extremity, and peripheral nerve (28.3 percent) or nonaesthetic breast (16.1
      percent). The most frequently performed core procedural competencies (average
      case logs per resident) included breast reduction (65.3 +/- 33.9); open carpal
      tunnel release (46.7 +/- 34.2); breast reconstruction, implant-based (39.6 +/-
      20.5); and wound management (35.7 +/- 28.6). Sixty-two of 177 procedures were
      logged on average less than once in 5 years of residency, including escharotomy,
      temporal parietal fascia flap, Guyon canal release, and soft-tissue fillers.
      CONCLUSION: This study identifies areas of exposure and underexposure to plastic
      surgery core procedural competencies, and can help focus surgical education on
      areas of greater need for surgical skills training and acquisition.

PMID- 30239500
TI  - The Fibula Osteoseptocutaneous Flap: Concise Review, Goal-Oriented Surgical
      Technique, and Tips and Tricks.
AB  - The fibula osteoseptocutaneous flap is a workhorse flap for bone reconstruction.
      Mastery of the flap is essential for a rewarding reconstruction. However, there
      is no complete work on this versatile flap. The authors provide a concise review
      of the literature, address the myths and challenges associated with the flap, and
      describe their refined techniques for different reconstruction scenarios and
      possible anatomical variations.

PMID- 30239501
TI  - State Variations in Public Payer Reimbursement for Common Plastic Surgery
      Procedures.
AB  - BACKGROUND: Existing data suggest decreased willingness of plastic surgeons to
      participate in Medicare and Medicaid. Significant disparities exist in Medicare
      and Medicaid reimbursement for various general surgical procedures. The aims of
      this study were to investigate variations in Medicare and Medicaid reimbursement
      across the nation for common plastic surgery procedures. METHODS: Medicare and
      Medicaid reimbursement data for 2017 were obtained by means of the Centers for
      Medicare & Medicaid Services and publicly available fee schedules from each
      state, respectively, for eight common plastic surgery procedures. The difference
      in Medicare and Medicaid reimbursement was calculated across all states. The
      difference in value ascribed to each procedure was determined by comparing the
      payment from each payer to the work relative value units. RESULTS: Medicaid
      reimbursement rates were significantly lower for the selected procedures, with a
      median national discount of -25 percent ($16.09 per work relative value unit)
      compared to Medicare. There were higher median rates of reimbursement per work
      relative value unit by Medicaid in only five states when compared to Medicare.
      Significant variations of more than 15 percent in the Medicaid-to-Medicare
      reimbursement ratios between our selected procedures were identified in 28
      states. CONCLUSIONS: Variations exist between Medicare and Medicaid reimbursement
      for common plastic surgery procedures. The within-state variations in Medicaid
      reimbursement are likely reflective of important yet nontransparent differences
      in determining Medicaid reimbursement. These variations likely affect access to
      care for underserved populations. Professional societies should continue to
      convey the value of these important procedures and raise awareness regarding
      disparities in access to care.

PMID- 30239502
TI  - Microvascular Hepatic Artery Anastomosis in Pediatric Living Donor Liver
      Transplantation: 73 Consecutive Cases Performed by a Single Surgeon.
AB  - BACKGROUND: Living donor liver transplantation is an important strategy of
      procuring segmental liver allografts for pediatric patients with liver failure,
      as suitably sized whole donor organs are scarce. The early pediatric living donor
      liver transplantation experience was associated with high rates of hepatic artery
      thrombosis, graft loss, and mortality. Collaboration with microsurgeons for
      hepatic artery anastomosis in pediatric living donor liver transplantation has
      decreased rates of arterial complications; however, reported outcomes are
      limited. METHODS: A 14-year retrospective review was undertaken of children at
      the authors' institution who underwent living donor liver transplantation with
      hepatic artery anastomosis performed by a single microsurgeon using an operating
      microscope. Data were collected on demographics, cause of liver failure, graft
      donor, vessel caliber, vessel anastomosis, arterial complications, and long-term
      follow-up. RESULTS: Seventy-three children with end-stage liver failure underwent
      living donor liver transplantation with microvascular hepatic artery anastomosis.
      The commonest cause for liver failure was biliary atresia (63 percent). A total
      of 83 end-to-end hepatic artery anastomoses were completed using an operating
      microscope. Hepatic artery complications occurred in five patients, consisting of
      three cases of kinked anastomoses that were revised without complications and two
      cases of hepatic artery thrombosis (3 percent), of which one resulted in graft
      loss and patient death. Patient survival was 94 percent at 1 year and 90 percent
      at 5 years. CONCLUSIONS: Microvascular hepatic artery anastomosis in pediatric
      patients undergoing living donor liver transplantation is associated with a low
      hepatic artery complication rate and excellent long-term liver graft function.
      Collaboration between microsurgeons and transplant surgeons can significantly
      reduce technical complications and improve patient outcomes. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 30239503
TI  - Benign Breast Diseases: An Introduction for the Advanced Practice Nurse.
AB  - The discovery of an abnormality in the breast may provoke anxiety for patient and
      clinician alike. Fortunately, most lesions in the breast are benign. Physical
      examination and breast imaging, including mammography, ultrasound, and magnetic
      resonance imaging, assist in the diagnosis of benign breast diseases.
      Understanding benign breast diseases is important for advanced practice nurses
      because these diseases are commonly seen in daily clinical practice.

PMID- 30239504
TI  - Head and Neck Cancer Survivors: Specific Needs and Their Implications for
      Survivorship Care Planning.
AB  - BACKGROUND: Head and neck cancer (HNC) survivors experience significant sequelae
      of treatment, including long-term physical side effects and ongoing cancer
      surveillance. OBJECTIVES: The aim of this study is to understand patients'
      survivorship knowledge gaps and supportive care needs. METHODS: Through an
      anonymous cross-sectional survey, the authors evaluated 41 HNC survivors'
      knowledge regarding post-treatment issues. FINDINGS: Patients had undergone a
      variety of treatment modalities.

PMID- 30239505
TI  - Height Measures: Evaluating Alternatives to Standing Height in the Ambulatory
      Setting.
AB  - BACKGROUND: Height measurement is a key clinical component to measure body mass
      index and body surface area used for patient care, including calculating
      chemotherapy doses. Some patients cannot feasibly or safely stand for height
      measurement because of a number of diseases and disabilities. The literature is
      unclear regarding alternatives to standing height for patients unable to stand.
      OBJECTIVES: The purpose of this research study was to test equivalence of a
      number of measurements to find a reliable alternative to standing height for
      ambulatory oncology clinic patients who are unable to or cannot safely stand.
      METHODS: A repeated-measures design was used to measure the height of 60
      volunteer adult participants using a convenience sample of 30 men and 30 women.
      Standing height was compared to self-reported height, recumbent length, arm span,
      half-arm span, demispan, and knee height measurements. FINDINGS: Results
      indicated that demispan was equivalent to standing height with a mean difference
      of -0.69. A practice change to use demispan in patients who cannot stand has been
      proposed and accepted at the authors' organization. The use of demispan was a
      feasible alternative to standing height in cost of supply and technique.

PMID- 30239506
TI  - How Do You Champion the Patient Navigator Role?
AB  - I worked for the Louisiana Tumor Registry for years, coding pathology reports and
      doing my part to make a difference, but ultimately, I grew bored. I wanted to
      hear the stories behind the reports I entered into a database and craved
      interaction with patients. When the opportunity to become a patient navigator
      presented itself, I jumped at the chance. I sold myself as an eager and capable
      member of the community who knew the patients' frustrations firsthand. I guess it
      worked, because I was hired by the Louisiana Cancer Control Program in July 2010
      as a patient navigator for patients beginning cancer treatment.

PMID- 30239507
TI  - An Islamic Perspective: Suffering and Meaning in Cancer.
AB  - Culturally competent care is contingent on knowledge of the unique values and
      attributes of diverse communities. This article focuses on Islamic perspectives
      of suffering and meaning in illness as they relate to cancer care. Personal
      narrative and evidence-based information are integrated to inform a holistic
      nursing approach to the care of Muslim patients, particularly when supporting
      them and their families through suffering in the context of malignancy or
      significant illness.

PMID- 30239508
TI  - Geographic Health Disparities: Satellite Clinics for Cancer Care in Rural
      Communities.
AB  - BACKGROUND: Cancer treatment is time-consuming and challenging for most patients,
      but particularly for those who live in geographically isolated areas. Satellite
      chemotherapy infusion centers offer a possible solution to geographic disparities
      in health care. OBJECTIVES: This article analyzes a satellite chemotherapy
      infusion center on the island of Martha's Vineyard in Massachusetts. METHODS:
      Interviews were conducted with staff of the infusion department of Martha's
      Vineyard Hospital, which has partnered with the cancer center at Massachusetts
      General Hospital to offer a satellite chemotherapy infusion center for island
      residents. FINDINGS: High-quality community hospitals are increasingly able to
      offer specialized oncology treatment and nursing care at greater convenience for
      patients through the use of satellite clinics.

PMID- 30239509
TI  - Afatinib Therapy: Practical Management of Adverse Events With an Oral Agent for
      Non-Small Cell Lung Cancer Treatment.
AB  - BACKGROUND: Afatinib is an oral, irreversible ErbB family blocker indicated for
      first-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients
      with non-resistant epidermal growth factor receptor (EGFR) mutations. Afatinib is
      also approved for the treatment of metastatic squamous NSCLC following
      progression on platinum-based chemotherapy. Common afatinib-associated toxicities
      include gastrointestinal and dermatologic events, which can be dose limiting.
      OBJECTIVES: In this review, the authors describe clinical trial experiences with
      afatinib, as well as best practices and practical approaches to the management of
      afatinib-associated adverse events in EGFR mutation-positive NSCLC. METHODS:
      Safety and tolerability data from phase 3 trials of afatinib were reviewed,
      together with real-life experiences from the authors' clinical practices.
      FINDINGS: Patient education, combined with early assessment and effective
      management of afatinib-related adverse events as well as dose- reduction
      strategies, allows patients to continue treatment and maximize the clinical
      benefits of afatinib.

PMID- 30239510
TI  - Targeted Therapy: New Radiolabeled Somatostatin Analogs to Treat
      Gastroenteropancreatic Neuroendocrine Tumors.
AB  - Neuroendocrine tumors (NETs), including gastroenteropancreatic NETs, or GEP-NETs,
      are heterogenous tumors that arise from diffuse neuroendocrine cells and other
      organs, such as the lung, ovary, and thyroid. Lutetium Lu 177 dotatate
      (Lutathera(r)) is a newly approved targeted therapy for patients with advanced
      GEP-NETs. Patients treated with octreotide long-acting release may be candidates
      for this second-line therapy. This article discusses lutetium Lu 177 dotatate
      therapy administration and patient care considerations.

PMID- 30239511
TI  - Multiple Myeloma Education: Results From the ACE Program's Digital, Serial
      Learning Approach.
AB  - BACKGROUND: Understanding aspects of multiple myeloma (MM) from drug delivery to
      side effect management and survivorship are critical to patient management. The
      Advanced Clinical Educator (ACE) program in MM combined live and web-based
      activities to educate nurses to gain mastery of content and achieve ACE status.
      OBJECTIVES: The primary objectives were to improve ACE candidates' practice
      skills and knowledge of MM and prepare them to educate others. METHODS: 20 ACE
      candidates were paired with an advisor and educated through a structured learning
      program. The RealMeasure(r) methodology measures the effect on intended learner
      cohorts, analyzing pre- and post-assessment data, as well as follow-up data, with
      a multidimensional metric that serves as a surrogate marker for performance.
      FINDINGS: Learners from the ACE program and a national cohort improved
      substantially from baseline averages at pretest to high levels of proficiency at
      post-test. This curriculum model fosters subject matter expertise, leadership,
      professional networking, and peer-to-peer learning.

PMID- 30239512
TI  - Scalp Cooling: Implementation of a Program at a Multisite Organization.
AB  - BACKGROUND: Chemotherapy-induced alopecia is a well-known side effect of some
      types of cancer treatments. With U.S. Food and Drug Administration clearance of
      two scalp cooling machines, patients with cancer now have the opportunity to
      minimize this hair loss. However, multiple barriers can exist for organizations
      when establishing a scalp cooling program. OBJECTIVES: This article describes the
      experience of a large multisite organization that implemented a machine-based
      scalp cooling program. METHODS: Nursing staff led an interprofessional team that
      addressed components of the program. As a result, eight sites within the authors'
      organization simultaneously began offering scalp cooling via machine using a
      single unified process. This approach was then successfully replicated one year
      later to prepare six additional sites to launch scalp cooling for other solid
      tumor types beyond breast cancer. FINDINGS: Using a structured, collaborative,
      and interprofessional approach to the implementation of a scalp cooling program
      at the authors' institution allowed for standardization of care across sites.
      This approach can be replicated at other healthcare institutions.

PMID- 30239513
TI  - Access to Care.
AB  - More and more community cancer care centers are shifting the model of delivery.
      In two years, 423 individual clinic treatment sites have closed, 658 oncology
      practices have been acquired by hospital systems, and 359 practices have
      struggled financially. These statistics represent an 11.3% increase in the number
      of community cancer clinic closings and an 8% increase in the number of facility
      consolidations into hospital settings. Overall, since 2008, 13.8 practices per
      month have been affected by closings, hospital acquisitions, and corporate
      mergers.

PMID- 30239514
TI  - Workplace Wellness Programs: Educating Patients and Families About Discrimination
      Via Disclosure of Genetic Information.
AB  - Oncology nurses are advocates for the ethical and legal use of patients' genetic
      information. However, this information may be used to discriminate against
      individuals when they share it while participating in workplace wellness
      programs. Amendments to federal genetic discrimination laws may lead employees to
      being financially penalized for nondisclosure of their genetic information. This
      article stresses the importance of nurses being aware of these laws and pushing
      for policy revision to protect sensitive genetic information.

PMID- 30239515
TI  - Adolescent Cancer Survivors: A Literature Review of Psychological Effects
      Following Remission.
AB  - BACKGROUND: The psychological distress caused by cancer can remain long after
      remission. With advanced curative treatments, many pediatric patients continue to
      have late complications that interfere with neurologic, physical, and social
      development. OBJECTIVES: The aim of this article is to analyze nine published
      articles that focus on adolescent cancer survivors (ACSs) and the incidence and
      risk factors of post-traumatic stress disorder (PTSD) and post-traumatic stress
      symptoms (PTSSs). METHODS: A search of published articles including pediatric and
      adolescent oncology and PTSD was performed. The search was narrowed to peer
      reviewed articles published after 2010 that presented empirical data and were
      specific to post-trauma or post-traumatic stress. FINDINGS: Significant findings
      for PTSD and PTSSs were reported in ACSs. ACSs suffering from PTSD and PTSSs
      should be identified and treated appropriately based on age, diagnosis,
      treatment, and comorbid symptoms.

PMID- 30239516
TI  - Chemotherapy-Induced Peripheral Neuropathy: Use of an Electronic Care Planning
      System to Improve Adherence to Recommended Assessment and Management Practices.
AB  - BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is often
      inadequately assessed and managed by advanced practice providers. OBJECTIVES: The
      aim is to explore the impact of CIPN assessment training and electronic care
      planning system (CPS) use on CIPN assessment documentation and guidelines
      adherence. METHODS: The authors used a pre-/post-test, prospective design with
      two retrospective chart reviews. Six providers received CIPN assessment training
      and used the CPS to manage CIPN for 75 women receiving neurotoxic chemotherapy.
      FINDINGS: CPS use significantly improved documentation of numbness and nonpainful
      CIPN management strategies but had no effect on documentation of additional
      assessment variables or painful CIPN management.

PMID- 30239517
TI  - Response to "Nephrotoxicity: Evidence in Patients Receiving Cisplatin Therapy".
AB  - An article by Duffy, Fitzgerald, Boyle, and Rohatgi (2018) was published in the
      April issue of the Clinical Journal of Oncology Nursing. Based on review, the
      authors suggested some clinical recommendations to protect the kidneys against
      cisplatin-induced nephrotoxicity, including hydration or supplementation of
      magnesium or mannitol during cisplatin administration. In addition to clinical
      findings, the related basic sciences data may be helpful in formulating treatment
      guidelines in cisplatin therapy. This letter will present several suggestions for
      future clinical studies based on laboratory findings.

PMID- 30239518
TI  - Oncology Nurse Practitioner Role: Recommendations From the Oncology Nursing
      Society's Nurse Practitioner Summit.
AB  - BACKGROUND: Oncology nurse practitioners (ONPs) are advanced practice RNs
      prepared at the graduate level with high-level knowledge and skills in oncology.
      Because of challenges in educational programs and variability in the scope of
      practice at the state and institutional level, many ONPs are challenged to
      practice to the full extent of their education, certification, and licensure.
      OBJECTIVES: The purpose of this article is to review issues affecting the
      education and practice patterns of ONPs and to identify solutions to address the
      challenges that exist for ONPs. METHODS: Members of the Oncology Nursing
      Society's Nurse Practitioner Summit summarized the challenges faced by ONPs
      related to education, training, practice, and professional development. FINDINGS:
      Efforts to promote ONP practice at the fullest extent of licensure and across
      various settings should be prioritized. Resources must be devoted to education,
      onboarding, and retention to integrate and retain ONPs as leaders of the
      interprofessional team.

PMID- 30239519
TI  - Oral Cryotherapy: Prevention of Oral Mucositis and Pain Among Patients With
      Colorectal Cancer Undergoing Chemotherapy.
AB  - BACKGROUND: Evidence remains mixed on the benefits of oral cryotherapy in the
      prevention of oral mucositis and pain associated with fluorouracil-based
      chemotherapy. OBJECTIVES: The intent of this article is to evaluate the effect of
      oral cryotherapy on the prevention of oral mucositis and pain among patients with
      colorectal cancer undergoing fluorouracil-based chemotherapy. METHODS: Using an
      experimental study design, the authors randomly assigned 80 patients to either
      the intervention (n = 40) or usual care group (n = 40). Intervention group
      participants received oral cryotherapy in the form of ice chips held in their
      mouths during chemotherapy infusion. Both groups used sodium bicarbonate
      mouthwash postchemotherapy until the next cycle. FINDINGS: In the usual care
      group, most participants reported grade 2 (moderate to life-threatening) or
      greater mucositis. Pain associated with mucositis was lower using oral
      cryotherapy, with the majority of participants in the intervention group
      reporting no pain.

PMID- 30239520
TI  - Multidisciplinary Cancer Care Model: A Positive Association Between Oncology
      Nurse Navigation and Improved Outcomes for Patients With Cancer.
AB  - BACKGROUND: Patients with cancer often experience prominent deficiencies in
      cancer care in the immediate period following initial cancer diagnosis.
      OBJECTIVES: This article aims to determine whether the inclusion of a
      gastrointestinal (GI) oncology nurse navigator (ONN) on the multidisciplinary
      cancer care team is associated with improved quality of care for patients.
      METHODS: This retrospective study compared randomly selected patients with GI
      cancer with and without an ONN. Two endpoints, the time from diagnosis to
      treatment and the average number of missed appointments, were evaluated through a
      review of healthcare records using the Epic electronic health records system.
      FINDINGS: Patients with an ONN had a shorter time lapse between diagnosis and
      treatment commencement (p < 0.001). In this group, the average time spent between
      initial diagnosis and the start of treatment was 15.15 days, compared to 42.93
      days for patients who were not part of the multidisciplinary cancer care model.

PMID- 30239521
TI  - Male Breast Cancer: Examining Gender Disparity in Diagnosis and Treatment.
AB  - BACKGROUND: Although men make up a small percentage of those diagnosed with
      breast cancer, they are usually diagnosed at a later stage than women, increasing
      their chance of mortality. The reasons for this gender disparity require
      additional study. OBJECTIVES: This article examines current literature on male
      breast cancer, including reasons for the gender disparity and interventions that
      may help to address it. METHODS: An integrative review was conducted, and 12
      studies were selected for inclusion. FINDINGS: Study consensus is that male
      breast cancer is an underresearched subject and that increased research efforts
      may improve outcomes. In addition, interventions could help to decrease the
      gender disparity in breast cancer detection.

PMID- 30239522
TI  - Care Coordination: Overcoming Barriers to Improve Outcomes for Patients With
      Hematologic Malignancies in Rural Settings.
AB  - BACKGROUND: Most patients with cancer experience financial, emotional, and
      logistical barriers to care that significantly affect their adherence to and
      successful completion of treatment. However, patients with hematologic
      malignancies, particularly those who live in rural settings, must also contend
      with additional challenges. OBJECTIVES: This article aims to synthesize the
      literature about barriers to timely access to care and to coordination of this
      care for patients with hematologic malignancies, particularly those in rural
      settings, as well as identify strategies to improve cancer care delivery for
      those patients. METHODS: A search of the literature from 2008-2018 pertaining to
      rural health disparities for patients with hematologic malignancies, along with
      ways to overcome these disparities, was conducted. FINDINGS: Patients with
      hematologic malignancies, particularly those who reside in rural settings, face
      complex barriers to care. These barriers cause emotional and physical distress. A
      team approach to care coordination that is focused on eliminating these barriers
      and improving outcomes is needed.

PMID- 30239523
TI  - Conversations With Patients: A Recipe for Providing Better, More Personalized
      Care.
AB  - The best gift a patient ever gave me was a recipe. It was handwritten on a small
      piece of lined paper, all in capital letters. The recipe was for zucchini bread
      and was given to me by Mr. S, a lung cancer survivor in his early 80s who I had
      been following in the cancer survivorship clinic that I started at the VA where I
      work in New England. He came to see me every three to six months for clinic
      visits and computed tomography scans to monitor for recurrence of his lung
      cancer.

PMID- 30239524
TI  - Caring for Staff: The Role of Psychiatric Mental Health Advanced Practice RNs in
      Supporting Oncology Nurses.
AB  - Compassion fatigue and burnout are well-established experiences for oncology
      nurses, often resulting in distress and reduced job satisfaction and prompting
      nurses to leave the profession altogether. Multiple interventions have been
      developed to better support nurses experiencing these phenomena, with varying
      success.

PMID- 30239525
TI  - Vapocoolant Sprays: Use With Totally Implanted Venous Access Devices.
AB  - Vapocoolant sprays are used in some facilities to manage pain associated with
      accessing totally implanted venous access devices (TIVADs). They are neither
      indicated nor contraindicated, and literature supporting safe and effective use
      within this process is lacking. The purpose of this article is to evaluate the
      use of vapocoolant sprays within the TIVAD access process and to facilitate best
      practice accounting for product use and safety, institutional policy, and
      individual patient needs.

PMID- 30239526
TI  - Crucial Conversations: Addressing Informational Needs of Adolescents and Young
      Adults Diagnosed With Cancer.
AB  - Adolescents and young adults (AYAs) with cancer aged 15-39 years have unique
      medical, psychosocial, and informational needs. At the time of diagnosis, they
      are often going through important life milestones, such as establishing their
      independence, attending school or work, and maintaining romantic and/or family
      relationships. This article describes some of the critical time points for AYAs
      with cancer and the resources available to support the nursing profession in
      meeting the unique care needs of this population.

PMID- 30239527
TI  - Approval Process: An Overview of Biosimilars in the Oncology Setting.
AB  - BACKGROUND: Following approval of the Biologics Price Competition and Innovation
      Act of 2009, biosimilars are gradually entering the market in the United States.
      With the introduction of more biosimilars into the marketplace, all healthcare
      providers should be familiar with the approval and evaluation process, the naming
      convention applied to these agents, and the importance of accurate
      pharmacovigilance. OBJECTIVES: This article aims to describe the approval process
      of biosimilars, including extrapolation, and to help healthcare providers
      understand when a biosimilar may be interchanged for the reference biologic and
      the naming convention used for biosimilars. In addition, this article explores
      how these topics affect confidence in dispensing and pharmacovigilance. METHODS:
      A literature review was conducted, and search terms and variation included
      biosimilar agents AND FDA approval, legislation, interchangeability, naming
      conventions, confidence in dispensing, and pharmacovigilance. FINDINGS:
      Healthcare providers involved in the dispensing and administration of biosimilar
      and interchangeable biologics need to be continually educated to ensure
      confidence, familiarity, and accuracy with the processes surrounding biosimilars.

PMID- 30239528
TI  - Clinical Trials: Nursing Roles During the Approval Process and Pharmacovigilance
      of Biosimilars.
AB  - BACKGROUND: The development of biosimilars is occurring more rapidly as patents
      on biologics expire. Oncology nurses will have an integral role in the new era of
      biosimilars regarding administration and education. OBJECTIVES: The purpose of
      this article is to review the role of the oncology nurse during biosimilar
      clinical trials, including regulatory guidelines, comparability exercise,
      clinical trial designs, and extrapolation of clinical trial data. This article
      also reviews pharmacovigilance. METHODS: A literature search was performed using
      various databases, and U.S. regulatory agency websites were searched for
      guidelines. FINDINGS: The role of the oncology nurse during biosimilar clinical
      trials includes assessment, monitoring, and reporting of adverse drug reactions
      associated with a biosimilar. Oncology nurses have key roles in pharmacovigilance
      of biosimilars, particularly in tracing, monitoring, and accurate reporting of
      adverse events associated with a specific biosimilar. Oncology nurses and
      patients must be educated on the proper reporting of adverse events.

PMID- 30239529
TI  - Biosimilars: Exploring the History, Science, and Progress.
AB  - BACKGROUND: Biosimilars provide opportunities for improving healthcare access and
      outcomes and reducing overall healthcare costs for patients with cancer.
      OBJECTIVES: The purpose of this article is to explore the history of biosimilars,
      regulatory pathways, and barriers to biosimilar approval. This article also aims
      to describe the patient and clinician barriers to biosimilars use and the
      progress that has been achieved since the first biosimilar approval in Europe in
      2006 and in the United States in 2015. METHODS: A literature search was conducted
      to retrieve articles that are highly relevant to the history of biosimilars
      development and regulatory pathways in the United States, Europe, Asia, and
      Canada. Patient and clinician perspectives on safety issues and concerns
      regarding immunogenicity and bioequivalence that limit use of biosimilars are
      also included. FINDINGS: Patient and provider concerns regarding immunologic
      patient safety issues, such as immunogenicity, lack of comparability, and low
      biosimilarity, still exist. The clinical safety, efficacy, and tolerability of
      biosimilars are among the top concerns in patients, prescribers, and clinicians.

PMID- 30239530
TI  - Nursing Roles: Clinical Implications Regarding Trends, Administration, and
      Education for Biosimilars in Oncology Practice.
AB  - BACKGROUND: With the advent of biosimilars into the U.S. healthcare market,
      knowledge deficits exist for nurses and patients regarding the regulatory
      approval process and key nursing considerations for each of these new
      medications. OBJECTIVES: This article provides essential clinical information for
      oncology nurses who are directly involved in patient care who will be
      administering U.S. Food and Drug Administration (FDA)-approved biosimilars for
      oncologic use. Oncology nurses must be informed on their therapeutic uses,
      mechanisms of action, and administration considerations. METHODS: An overview of
      biosimilars in the United States is given, and each FDA-approved oncology
      biosimilar medication is described in detail. FINDINGS: Oncology biosimilars are
      safe and effective treatment options that may increase patient access, decrease
      healthcare costs through competition, and improve the lives of patients with
      certain malignancies. Nurses are in key roles in patient care to foster the
      transition from previously patented, branded, and expensive medications to
      biosimilars that can achieve the same desired effects for a lower cost.

PMID- 30239531
TI  - A fracture, a family, legal entanglement, expensive investigation, and a familiar
      disease.
AB  - Osteogenesis imperfecta can be commonly mistaken for child abuse because of
      similar pattern of injuries. AA is a 3-week-old baby who presented to our
      emergency department with excessive crying. Skeletal survey revealed subacute
      spiral fracture of the right humerus, right posterior eighth and ninth ribs,
      acute fracture of the left femur, bowing of tibia and femur, and osteopenia.
      Subsequent geneticist examination and genetic testing noted blue sclera and
      heterozygosity for a variant of COL1A gene.

PMID- 30239532
TI  - On Motivational Interviewing for Oral Health Promotion: State of the Field and
      Future Directions.
AB  - Knowledge Transfer Statement: Behavior is important in dental disease etiology,
      so behavioral interventions are needed for prevention and treatment. Motivational
      interviewing has been proposed as a potentially useful behavioral intervention
      for oral health promotion, but results from published studies are mixed.
      Furthermore, this literature is immature; basic efficacy research and innovative
      applications are still needed. Although likely not as a stand-alone intervention,
      motivational interviewing may hold promise for dental public health.

PMID- 30239533
TI  - Editorial: Best Papers of 2009.

PMID- 30239534
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1002/prp2.2.70.].

PMID- 30239535
TI  - Editorial.

PMID- 30239536
TI  - A mussel-inspired chimeric protein as a novel facile antifouling coating.
AB  - A mussel-inspired chimeric protein as a multifunctional coating was engineered
      rationally and applied in antifouling. 3,4-Dihydroxyphenyl-alanine (Dopa) and
      zwitterionic peptides inspired from molecular chaperones were incorporated into
      the designed protein. The multifunctional protein coating can anchor onto various
      substrates surfaces readily and exhibits superior antifouling properties.

PMID- 30239537
TI  - Efficient and durable N2 reduction electrocatalysis under ambient conditions:
      beta-FeOOH nanorods as a non-noble-metal catalyst.
AB  - NH3 is one of the most important chemicals with a wide range of applications. NH3
      is mainly produced via the Haber-Bosch process, which leads to large energy
      consumption and carbon emission. Electrochemical reduction has emerged as an
      environmentally-benign and sustainable alternative for artificial N2 fixation
      under ambient conditions, but needs materials to effectively catalyze the N2
      reduction reaction (NRR). In this communication, we report that beta-FeOOH
      nanorods behave as an efficient and durable NRR electrocatalyst. In 0.5 M LiClO4,
      such an electrocatalyst achieves a high NH3 yield of 23.32 MUg h-1 mgcat.-1 and a
      faradaic efficiency of 6.7%, outperforming most reported aqueous-based NRR
      electrocatalysts under ambient conditions. Notably, this catalyst also shows good
      electrochemical stability and excellent selectivity. The catalytic mechanism of
      the NRR on the FeOOH(110) surface is further discussed using density functional
      theory calculations.

PMID- 30239538
TI  - The semiquinone radical anion of 1,10-phenanthroline-5,6-dione: synthesis and
      rare earth coordination chemistry.
AB  - Reduction of 1,10-phenanthroline-5,6-dione (pd) with CoCpR2 resulted in the first
      molecular compounds of the pd- semi-quinone radical anion, [CoCpR2]+[pd]- (R = H,
      (1); R = Me4, (2)). Furthermore compounds 1 and 2 were reacted with
      [Y(hfac)3(thf)2] (hfac = 1,1,1-5,5,5-hexafluoroacetylacetonate) to synthesise the
      rare earth-transition metal heterometallic compounds, [CoCpR2]+[Y(hfac)3(N,N'
      pd)]- (R = H, (3); R = Me4, (4)).

PMID- 30239539
TI  - The rotational spectrum of 15ND. Isotopic-independent Dunham-type analysis of the
      imidogen radical.
AB  - The rotational spectrum of 15ND in its ground electronic X3Sigma- state has been
      observed for the first time. Forty-three hyperfine-structure components belonging
      to the ground and nu = 1 vibrational states have been recorded with a frequency
      modulation millimeter-/submillimeter-wave spectrometer. These new measurements,
      together with the ones available for the other isotopologues NH, ND, and 15NH,
      have been simultaneously analysed using the Dunham model to represent the ro
      vibrational, fine, and hyperfine energy contributions. The least-squares fit of
      more than 1500 transitions yielded an extensive set of isotopically independent
      Ulm parameters plus 13 Born-Oppenheimer Breakdown coefficients Deltalm. As an
      alternative approach, we performed a Dunham analysis in terms of the most
      abundant isotopologue coefficients Ylm and some isotopically dependent Born
      Oppenheimer Breakdown constants deltalm [R. J. Le Roy, J. Mol. Spectrosc., 1999,
      194, 189]. The two fits provide results of equivalent quality. The Born
      Oppenheimer equilibrium bond distance for the imidogen radical has been
      calculated [rBOe = 103.606721(13) pm] and zero-point energies have been derived
      for all the isotopologues.

PMID- 30239540
TI  - De novo assembly and comparative transcriptome characterization of Poecilobdella
      javanica provide insight into blood feeding of medicinal leeches.
AB  - Leeches (family Hirudinidae) are classic model invertebrates used in diverse
      clinical treatments, such as reconstructive microsurgery, hypertension, and
      gangrene treatment. The blood-feeding habit is essential for these therapies, yet
      the molecular mechanisms underlying the process are poorly understood. In the
      present study, the transcriptome of Poecilobdella javanica from five time points
      (days 0, 1, 10, 20, and 30 separately) of blood feeding was sequenced with short
      paired-end reads. After stringent quality control, ~380 million high-quality
      reads were assembled using SOAPdenovo-Trans with optimal parameters into a non
      redundant set of 48 784 transcripts (>=100 base pairs), representing about 38 Mb
      of unique transcriptome sequence. The average length of the transcripts was 570
      bp with N50 lengths of 5751 to 7413 bp among different time points. We have
      assessed the effect of sequence quality and various assembly parameters on the
      final assembly output. Functional categorization revealed the conservation of
      genes involved in various biological processes, such as basal transcription
      factors and ribosome biogenesis in eukaryotes. In addition, we found that DNA/RNA
      related pathways were predominantly expressed in the starving state while fatty
      acid metabolism, the anticoagulant pathway, and amino acid biosynthesis were
      activated during blood feeding. The leech transcriptome provides a resource for
      gene discovery and development of functional molecular markers during clinical
      applications.

PMID- 30239541
TI  - [(H2O)Zn(Imidazole)n]2+: the vital roles of coordination number and geometry in
      Zn-OH2 acidity and catalytic hydrolysis.
AB  - The Zn(ii)-(Imidazole(ate))n coordination motif occurs in numerous biochemical
      systems, including carbonic anhydrase and the matrix metalloproteinases (MMPs).
      Additionally, it has been used in synthetic materials, such as the zinc-based
      zeolitic imidazolate framework (ZIF) structures. Zinc centers in these systems
      typically act as Lewis acids that form complexes with small molecules, such as
      H2O, which is activated catalytically toward a number of important and useful
      hydrolysis reactions. The results reported herein from density functional theory
      (M05-2X) and ab initio (MP2 and CCSD(T)) calculations demonstrate that both the
      coordination number and the molecular geometry have a sizable impact on the
      binding strength, deprotonation energy, and acidity of the Zn(ii) coordinated
      water. Through a series of quantum mechanical calculations on [(ImH)nZn-OH2]2+
      complexes (n = 1-5), both the solution-phase pKa and the gas-phase proton
      dissociation energy significantly increase as n increases. While this should not
      be too surprising, the Zn-OH2 bond dissociation energies and bond lengths don't
      necessarily undergo a concurrent decrease, and therefore would be of limited use
      as a prediction tool regarding Zn-OH2 acidity. In an effort to dissect the
      impacts of coordination number and molecular geometry on these thermodynamic
      parameters, we performed constrained geometry optimizations on the three- (n = 2)
      and four-coordinate (n = 3) complexes. These calculations surprisingly reveal a
      marked impact on the pKa and proton dissociation energy of the coordinated water,
      upon exclusive changes in the Zn(ii) coordination geometry, whether in the gas
      phase or in aqueous solution. We discuss the relevance of these results to the
      catalytic peptide hydrolysis mechanism of the MMPs and possible implications for
      catalytic activity within or on the surfaces of ZIFs.

PMID- 30239542
TI  - Root-growth of boron nitride nanotubes: experiments and ab initio simulations.
AB  - We have synthesized boron nitride nanotubes (BNNTs) in an arc in the presence of
      boron and nitrogen species. We find that BNNTs are often attached to large
      nanoparticles, suggesting that root-growth is a likely mechanism for their
      formation. Moreover, the tube-end nanoparticles are composed of boron, without
      transition metals, indicating that transition metals are not necessary for the
      arc synthesis of BNNTs. To gain further insight into this process we have studied
      key mechanisms for root growth of BNNTs on the surface of a liquid boron droplet
      by ab initio molecular dynamics simulations. We find that nitrogen atoms reside
      predominantly on the droplet surface where they organize to form boron nitride
      islands below 2400 K. To minimize contact with the liquid particle underneath,
      the islands assume non-planar configurations that are likely precursors for the
      thermal nucleation of cap structures. Once formed, the caps are stable and can
      easily incorporate nitrogen and boron atoms at their base, resulting in further
      growth. Our simulations support the root-growth mechanism of BNNTs and provide
      comprehensive evidence of the active role played by liquid boron.

PMID- 30239543
TI  - Recent developments in Zintl cluster chemistry.
AB  - Zintl anions have been known for more than a century and were studied
      systematically by Eduard Zintl in the 1930s. Since then, they have been
      investigated for their interesting structures, bonding, and physical properties -
      in solid Zintl phases, in solvate salts, and in solution. While their popularity
      remained limited for several decades, Zintl ion chemistry has recently
      experienced a renaissance as a result of breakthroughs regarding their
      modifications into multinary anions that include transition metal atoms, their
      organic derivatization, and their oxidative linkage. A plethora of reports from
      the past two decades - demonstrating the ever growing variety of Zintl ion
      chemistry - have been since summarized in several review articles. Herein, we
      intend to present the most recent developments, which also shed light on Zintl
      anions and clusters as useful precursors for materials development, as
      illustrated by one recent example.

PMID- 30239544
TI  - The affinity of MhuD for heme is consistent with a heme degrading function in
      vivo.
AB  - MhuD is a protein found in mycobacteria that can bind up to two heme molecules
      per protein monomer and catalyze the degradation of heme to mycobilin in vitro.
      Here the Kd1 for heme dissociation from heme-bound MhuD was determined to be 7.6
      +/- 0.8 nM and the Kd2 for heme dissocation from diheme-bound MhuD was determined
      to be 3.3 +/- 1.1 MUM. These data strongly suggest that MhuD is a competent heme
      oxygenase in vivo.

PMID- 30239545
TI  - Theoretical investigations on hydrogen peroxide decomposition in aquo.
AB  - Hydrogen peroxide (H2O2) decomposition mechanisms in the absence and presence of
      iron ions in aqueous solution, which contain no OH radical formation, are
      theoretically determined. Calculating the oxygen-oxygen bond dissociation
      energies of H2O2, we confirmed that OH radical formation requires spin-forbidden
      transitions. Instead, we tested an H2O2 dimer-based decomposition mechanism and
      found that this mechanism provides reasonable barrier heights of 52-62 kcal mol
      1, which are close to the experimental activation energy. We next calculated the
      oxygen-oxygen bond dissociation of H2O2 coordinating to the iron ion hydration
      complex in order to explore H2O2 decomposition in the presence of iron ions.
      Surprisingly, we found that a monovalent iron ion complex provides no reaction
      barrier to dissociate H2O2, in contrast to the ferrous (Fe2+) and ferric (Fe3+)
      ion complexes with accompanying very high barriers. Following this result, we
      determined the subsequent oxygen formation mechanism of the monovalent iron ion
      complex and found that this mechanism needs a hydrogen bond network around H2O2
      to proceed at room temperature. We, therefore, conclude that H2O2 decomposition
      in the presence of iron ions is driven by electron transfer to the iron ion
      hydration complex and proceeds by hydrogen transfers in the hydrogen bond network
      around H2O2.

PMID- 30239546
TI  - Synthesis of 3-substituted quinolin-2(1H)-ones via the cyclization of o
      alkynylisocyanobenzenes.
AB  - A facile synthesis of various functionalized 3-substituted quinolin-2(1H)-ones
      through Ag(i) nitrate-catalyzed cyclization of o-alkynylisocyanobenzenes is
      described. The reaction allows rapid and convenient access to 3-substituted
      quinolin-2(1H)-one scaffolds in moderate to good yields.

PMID- 30239547
TI  - The impact of lipid oxidation on the functioning of a lung surfactant model.
AB  - Apart from being responsible for sufficient pulmonary compliance and preventing
      alveolar collapse, lung surfactant (LS) also forms the first barrier for uptake
      of inhaled pathogens. As such it is susceptible to damage caused by various
      deleterious compounds present in air, e.g. oxidants capable of oxidizing
      unsaturated LS lipids. This study examines the consequences of oxidizing 20% of
      unsaturated lipids in an LS model: a mixed 1 : 1 DPPC : POPC monolayer. POxnoPC
      (1-palmitoyl-2-(9-oxo-nonanoyl)-sn-glycero-3-phosphocholine) is considered as the
      main oxidation product. Experimental surface pressure-area isotherms and
      polarization-modulation infrared reflection-absorption spectroscopy are employed
      to probe changes in the macroscopic properties of the unsaturated lipid monolayer
      induced by oxidation. Microscopic details of the influence of oxidation on the
      monolayer's phase behavior are elucidated by molecular dynamics simulations at
      varying lipid packing. We demonstrate that unsaturated lipid oxidation shifts the
      isotherm towards larger areas and advances monolayer collapse. This is caused by
      a reversal of the oxidized sn-2 chains of POxnoPC towards the subphase, driven by
      electrostatic interactions between the aldehyde, glycerin, and water. Increased
      lipid bulkiness, hindered transition to the LC phase, and transfer of oxidized
      chain terminals to the subphase have been identified as the most troublesome
      consequences of this process. They result in the reduction of monolayer stability
      and its capability to withstand high surface pressures. This may lead to
      uncontrolled and irreversible loss of lipids from the surface.

PMID- 30239548
TI  - Graphene-based biosensor for on-chip detection of bio-orthogonally labeled
      proteins to identify the circulating biomarkers of aging during heterochronic
      parabiosis.
AB  - Studies of heterochronic parabiosis, where two animals of different ages are
      joined surgically, provided proof-of-principle results that systemic proteins
      have broad age-specific effects on tissue health and repair. In an effort to
      identify these systemic proteins, we previously developed a method to selectively
      label the proteome of only one animal joined in parabiosis utilizing bio
      orthogonal non-canonical amino acid tagging (BONCAT), which can metabolically
      label proteins during their de novo synthesis by incorporating a methionine
      substitute, azido-nor-leucine (ANL), in cells expressing a mutant methionyl-tRNA
      synthetase (MetRSL274G). Once labeled, we can selectively identify the proteins
      produced by the MetRSL274G transgenic mouse in the setting of heterochronic
      parabiosis. This approach enabled the detection of several rejuvenating protein
      candidates from the young parabiont, which were transferred to the old mammalian
      tissue through their shared circulation. Although BONCAT is a very powerful
      technology, the challenges associated with its complexity including large
      starting material requirements and cost of ANL-labeled protein detection, such as
      modified antibody arrays and mass spectrometry, limit its application. Herein, we
      propose a lab-on-a-chip technology, termed Click-A+Chip for facile and rapid
      digital detection of ANL-labeled proteomes present in minute amount of sample, to
      replace conventional assays. Click-A+Chip is a graphene-based field effect
      biosensor (gFEB) which utilizes novel on-chip click-chemistry to specifically
      bind to ANL-labeled biomolecules. In this study, Click-A+Chip is utilized for the
      capture of ANL-labeled proteins transferred from young to old parabiotic mouse
      partners. Moreover, we were able to identify the young-derived ANL-labeled Lif-1
      and leptin in parabiotic systemic milieu, confirming previous data as well as
      providing novel findings on the relative levels of these factors in young versus
      old parabionts. Summarily, our results demonstrate that Click-A+Chip can be used
      for rapid detection and identification of ANL-labeled proteins, significantly
      reducing the sample size, complexity, cost and time associated with BONCAT
      analysis.

PMID- 30239550
TI  - Differential effects of medium- and long-chain saturated fatty acids on blood
      lipid profile: a systematic review and meta-analysis.
AB  - Background: Medium-chain saturated fatty acids (MCFAs) may affect circulating
      lipids and lipoproteins differently than long-chain saturated fatty acids
      (LCSFAs), but the results from human intervention trials have been equivocal.
      Objective: The aim of this study was to determine whether MCFAs and LCSFAs have
      differential impacts on blood lipids and lipoproteins. Design: Five databases
      were searched (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus) until April 2018,
      and published clinical trials investigating the differential effects of dietary
      MCFAs and LCSFAs on blood lipids were included. Searches were limited to the
      English language and to studies with adults aged >18 y. Where possible, studies
      were pooled for meta-analysis using RevMan 5.2. The principle summary measure was
      the mean difference between groups calculated using the random-effects model.
      Results: Eleven eligible crossover and 1 parallel trial were identified with a
      total of 299 participants [weighted mean +/- SD age: 38 +/- 3 y; weighted mean +/
      SD body mass index (kg/m2): 24 +/- 2]. All studies were pooled for the meta
      analysis. Diets enriched with MCFAs led to significantly higher high-density
      lipoprotein (HDL) cholesterol concentrations than diets enriched with LCSFAs
      (0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L) with no effect on triglyceride, low
      density lipoprotein (LDL) cholesterol, and total cholesterol concentrations.
      Consumption of diets rich in MCFAs significantly increased apolipoprotein A-I
      (apoA-I) concentrations compared with diets rich in LCSFAs (0.08 g/L; 95% CI:
      0.02, 0.14 g/L). There was no evidence of statistical heterogeneity for HDL
      cholesterol, apoA-I, and triglyceride concentrations; however, significant
      heterogeneity was observed for the total cholesterol (I2 = 49%) and LDL
      cholesterol analysis (I2 = 58%). Conclusion: The findings of this research
      demonstrate a differential effect of MCFAs and LCSFAs on HDL cholesterol
      concentrations. Further investigations are warranted to elucidate the mechanism
      by which the lipid profile is altered. This trial was registered at
      www.crd.york.ac.uk/PROSPERO as CRD42017078277.

PMID- 30239551
TI  - Cell-free DNA derived from cancer cells facilitates tumor malignancy through Toll
      like receptor 9 signaling-triggered interleukin-8 secretion in colorectal cancer.
AB  - Circulating cell-free DNA (cfDNA) has become a potential diagnostic and
      prognostic biomarker for colorectal cancer (CRC). In non-cancerous diseases, it
      has been confirmed that cfDNA can be recognized by Toll-like receptor 9 (TLR9),
      leading to a significant biological change. Nevertheless, the biological
      significance of cfDNA and its relationship with TLR9 in tumor malignancy is still
      unclear. Therefore, the purpose of this study is to explore the biological role
      of cfDNA in colorectal cancer (CRC). The expression of TLR9 was measured in
      different CRC cell lines and cancerous samples by RT-PCR or immunohistochemistry,
      which showed that high expression of TLR9 was significantly correlated with the
      tumor metastasis, advanced TNM stage and poor prognosis of patients. Then, cfDNA
      was obtained from fluorouracil (5FU)-induced apoptotic cancer cells in vitro and
      transfection techniques were used to transfect siRNA and cDNA plasmid for TLR9.
      Cancer cells were stimulated using isolated cfDNA fragments, and results showed
      that cfDNA could promote colorectal cancer cell proliferation via TLR9.
      Meanwhile, we demonstrated that the cfDNA binding to TLR9 could facilitate cell
      migration and invasion. Finally, we demonstrated that cfDNA initiated downstream
      TLR9-MyD88 signaling and induced robust release of chemokine interleukin 8 (IL
      8), which helped to elucidate the mechanisms underlying these phenomena. Our data
      suggest that cancer cell-derived cfDNA contributes to cancer progression through
      activation of TLR9-MyD88 signaling and IL-8 secretion in CRC. These findings
      provide a novel perspective for understanding of tumor progression and provoke a
      potential therapeutic target for CRC treatment.

PMID- 30239549
TI  - Intermittent bolus feeding promotes greater lean growth than continuous feeding
      in a neonatal piglet model.
AB  - Background: Orogastric tube feeding is indicated in neonates with an impaired
      ability to ingest food normally and can be administered with an intermittent
      bolus or continuous feeding schedule. Objectives: The objectives were to 1)
      compare the long-term effect of continuous with intermittent feeding on growth
      using the newborn pig as a model, 2) determine whether feeding frequency alters
      lean tissue and fat mass gain, and 3) identify the signaling mechanisms by which
      protein deposition is controlled in skeletal muscle in response to feeding
      frequency. Design: Neonatal pigs were fed the same amount of a balanced formula
      by orogastric tube either as an intermittent bolus meal every 4 h (INT) or as a
      continuous infusion (CON). Body composition was assessed at the start and end of
      the study by dual-energy X-ray absorptiometry, and hormone and substrate
      profiles, muscle mass, protein synthesis, and indexes of nutrient and insulin
      signaling were measured after 21 d. Results: Body weight, lean mass, spine
      length, and skeletal muscle mass were greater in the INT group than in the CON
      group. Skeletal muscle fractional protein synthesis rates were greater in the INT
      group after a meal than in the CON group and were associated with higher
      circulating branched-chain amino acid and insulin concentrations. Skeletal muscle
      protein kinase B (PKB) and ribosomal protein S6 kinase phosphorylation and
      eukaryotic initiation factor (eIF) 4E-eIF4G complex formation were higher,
      whereas eIF2alpha phosphorylation was lower in the INT group than in the CON
      group, indicating enhanced activation of insulin and amino acid signaling to
      translation initiation. Conclusions: These results suggest that when neonates are
      fed the same amounts of nutrients as intermittent meals rather than continuously
      there is greater lean growth. This response can be ascribed, in part, to the
      pulsatile pattern of amino acids, insulin, or both induced by INT, which enables
      the responsiveness of anabolic pathways to feeding to be sustained chronically in
      skeletal muscle.

PMID- 30239553
TI  - LncRNA HOTAIR mediates TGF-beta2-induced cell growth and epithelial-mesenchymal
      transition in human lens epithelial cells.
AB  - Posterior capsule opacification (PCO) results from the proliferation, migration,
      and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells
      (LECs) and fibers in the capsular bag. Previous reports have demonstrated that
      transforming growth factor beta2 (TGF-beta2) affects the cellular processes via
      modulation of EMT in LECs. However, the mechanisms that underlie the TGF-beta2
      induced EMT in LECs are still largely unknown. In this study, we confirmed that
      TGF-beta2 induces EMT in SRA01/04 cells via the up-regulation of the long non
      coding RNA (lncRNA) HOTAIR. To study the effects of HOTAIR on the proliferation,
      migration and EMT of SRA01/04 cells as well as the underlying mechanism, we used
      small interfering RNA (siRNA) to specifically attenuate HOTAIR expression in
      SRA01/04 cells. CCK8 cell-counting kit was used to examine SRA01/04 cell
      viability; EdU cell proliferation kit was used to examine SRA01/04 cell
      proliferation; Transwell system and scratch assays were used to observe cell
      migration; and qPCR and western blot analysis were used to evaluate EMT
      progression. We found that inhibition of HOTAIR expression repressed SRA01/04
      cell viability, proliferation, migration and prevented the TGF-beta2-induced
      changes in cellular processes via modulation of EMT. Ultimately, we found that
      HOTAIR affected the TGF-beta/Smad signaling pathway. In summary, we elucidated
      that HOTAIR affected the cell viability, proliferation, and migration in the TGF
      beta2-induced EMT in SRA01/04 cells and suggested that modulation of HOTAIR may
      be helpful in PCO prevention and therapy.

PMID- 30239552
TI  - Limited appearance of apocarotenoids is observed in plasma after consumption of
      tomato juices: a randomized human clinical trial.
AB  - Background: Nonvitamin A apocarotenoids occur in foods. Some function as retinoic
      acid receptor antagonists in vitro, though it is unclear if apocarotenoids are
      absorbed or accumulate to levels needed to elicit biological function. Objective:
      The aim of this study was to quantify carotenoids and apocarotenoids (beta-apo-8'
      , -10'-, -12'-, and -14'-carotenal, apo-6'-, -8'-, -10'-, -12'-, and -14'
      lycopenal, retinal, acycloretinal, beta-apo-13-carotenone, and apo-13-lycopenone)
      in human plasma after controlled consumption of carotenoid-rich tomato juices.
      Design: Healthy subjects (n = 35) consumed a low-carotenoid diet for 2 wk, then
      consumed 360 mL of high-beta-carotene tomato juice (30.4 mg of beta-carotene,
      34.5 MUg total beta-apocarotenoids/d), high-lycopene tomato juice (42.5 mg of
      lycopene, 119.2 MUg total apolycopenoids/d), or a carotenoid-free control
      (cucumber juice) per day for 4 wk. Plasma was sampled at baseline (after washout)
      and after 2 and 4 wk, and analyzed for carotenoids and apocarotenoids using high
      pressure liquid chromatography (HPLC) and HPLC-tandem mass spectrometry,
      respectively. The methods used to analyze the apocarotenoids had limits of
      detection of ~ 100 pmol/L. Results: Apocarotenoids are present in tomato juices
      at 0.1-0.5% of the parent carotenoids. Plasma lycopene and beta-carotene
      increased (P < 0.001) after consuming high-lycopene and beta-carotene tomato
      juices, respectively, while retinol remained unchanged. beta-Apo-13-carotenone
      was found in the blood of all subjects at every visit, although elevated (P <
      0.001) after consuming beta-carotene tomato juice for 4 wk (1.01 +/- 0.27 nmol/L)
      compared with both baseline (0.37 +/- 0.17 nmol/L) and control (0.46 +/- 0.11
      nmol/L). Apo-6'-lycopenal was detected or quantifiable in 29 subjects, while beta
      apo-10'- and 12'-carotenal were detected in 6 and 2 subjects, respectively. No
      other apolycopenoids or apocarotenoids were detected. Conclusions: beta-Apo-13
      carotenone was the only apocarotenoid that was quantifiable in all subjects, and
      was elevated in those consuming high-beta-carotene tomato juice. Levels were
      similar to previous reports of all-trans-retinoic acid. Other apocarotenoids are
      either poorly absorbed or rapidly metabolized or cleared, and so are absent or
      limited in blood. beta-Apo-13-carotenone may form from vitamin A and its presence
      warrants further investigation. This trial was registered at clinicaltrials.gov
      as NCT02550483.

PMID- 30239554
TI  - Adipose tissue and skeletal muscle insulin-mediated glucose uptake in insulin
      resistance: role of blood flow and diabetes.
AB  - Background: Adipose tissue glucose uptake is impaired in insulin-resistant
      states, but ex vivo studies of human adipose tissue have yielded heterogeneous
      results. This discrepancy may be due to different regulation of blood supply.
      Objective: The aim of this study was to test the flow dependency of in vivo
      insulin-mediated glucose uptake in fat tissues, and to contrast it with that of
      skeletal muscle. Design: We reanalyzed data from 159 individuals in which adipose
      tissue depots-subcutaneous abdominal and femoral, and intraperitoneal-and femoral
      skeletal muscle were identified by MRI, and insulin-stimulated glucose uptake
      ([18F]-fluoro-2-deoxyglucose) and blood flow ([15O]-H2O) were measured
      simultaneously by positron emission tomography scanning. Results: Individuals in
      the bottom tertile of whole-body glucose uptake [median (IQR) 36 (17) umol. kg
      fat-free mass (kgFFM)-1 . min-1 .nM-1] displayed all features of insulin
      resistance compared with the rest of the group [median (IQR) 97 (71) umol . kgFFM
      1 .min-1 . nM-1]. Rates of glucose uptake were directly related to the degree of
      insulin resistance in all fat depots as well as in skeletal muscle. However,
      blood flow was inversely related to insulin sensitivity in each fat depot (all P
      <= 0.03), whereas femoral muscle blood flow was not significantly different
      between insulin-resistant and insulin-sensitive subjects, and was not related to
      insulin sensitivity. Furthermore, in subjects performing one-leg exercise, blood
      flow increased 5- to 6-fold in femoral muscle but not in the overlying adipose
      tissue. The presence of diabetes was associated with a modest increase in fat and
      muscle glucose uptake independent of insulin resistance. Conclusions: Reduced
      blood supply is an important factor for the impairment of in vivo insulin
      mediated glucose uptake in both subcutaneous and visceral fat. In contrast, the
      insulin resistance of glucose uptake in resting skeletal muscle is predominantly
      a cellular defect. Diabetes provides a modest compensatory increase in fat and
      muscle glucose uptake that is independent of insulin resistance.

PMID- 30239555
TI  - Microbial enterotypes in personalized nutrition and obesity management.
AB  - Human gut microbiota has been suggested to play an important role in nutrition
      and obesity. However, formulating meaningful and clinically relevant dietary
      advice based on knowledge about gut microbiota remains a key challenge. A number
      of recent studies have found evidence that stratification of individuals
      according to 2 microbial enterotypes (dominance of either Prevotella or
      Bacteroides) may be useful in predicting responses to diets and drugs. Here, we
      review enterotypes in a nutritional context and discuss how enterotype
      stratification may be used in personalized nutrition in obesity management.
      Enterotypes are characterized by distinct digestive functions with preference for
      specific dietary substrate, resulting in short-chain fatty acids that may
      influence energy balance in the host. Consequently, the enterotype potentially
      affects the individual's ability to lose weight when following a specific diet.
      In short, a high-fiber diet seems to optimize weight loss among Prevotella
      enterotype subjects but not among Bacteroides-enterotype subjects. In contrast,
      increasing bifidobacteria in the gut among Bacteroides-enterotype subjects
      improves metabolic parameters, suggesting that this approach can be used as an
      alternative weight loss strategy. Thus, enterotypes, as a pretreatment gut
      microbiota biomarker, have the potential to become an important tool in
      personalized nutrition and obesity management, although further interventions
      assessing their applicability are warranted.

PMID- 30239556
TI  - Nutritionally Essential Amino Acids.
AB  - Amino acids (AAs) are defined as organic compounds containing both amino and acid
      groups (1). Proteinogenic AAs are AAs that serve as substrates for protein
      synthesis in animal cells, and occur naturally as L-AAs except for glycine. Free
      AAs (those AAs that are not constituents of peptides or polymers) in physiologic
      fluid exist primarily in an L-isoform, but some of them may be present in a D
      isoform. Based on his findings in 1912 that adult dogs exhibited a negative
      nitrogen balance when fed a tryptophan-free diet but maintained a positive
      nitrogen balance when fed a proline-free diet, Abderhalden (2) classified AAs as
      nutritionally essential (EAAs) or nonessential (NEAAs). Beginning in 1924, WC
      Rose and coworkers (3) published a series of landmark papers on AA nutrition and
      metabolism in rats and humans that further defined AAs as EAAs or NEAAs based on
      nitrogen balance or growth. We published an essay on NEAAs in 2017 (4), and EAAs
      are the focus of the present article.

PMID- 30239558
TI  - Fetal sex modifies the effect of maternal macronutrient intake on the incidence
      of small-for-gestational-age births: a prospective observational cohort study.
AB  - Background: Maternal macronutrient intake is likely to play a pivotal role in
      fetoplacental growth. Male fetuses grow faster and their growth is more
      responsive to maternal size. Objective: We assessed the role of fetal sex in
      modifying the effect of maternal macronutrient intake on the risk of small-for
      gestational-age (SGA) birth. Design: This was a prospective, observational cohort
      study of 2035 births from an urban South Asian Indian population. Maternal
      intakes of total energy and macronutrients were recorded by validated food
      frequency questionnaires. The interaction of trimester 1 macronutrient intake
      with fetal sex was tested on the outcome of SGA births. Results: The prevalence
      of SGA was 28%. Trimester 1 macronutrient composition was high in carbohydrate
      and low in fat (means +/- SDs-carbohydrate: 64.6% +/- 5.1%; protein: 11.5% +/-
      1.1%; and fat: 23.9% +/- 4.4% of energy). Higher carbohydrate and lower fat
      consumption were each associated with an increased risk of SGA [adjusted OR (AOR)
      per 5% of energy (95% CI): carbohydrate: 1.15 (1.01, 1.32); fat: 0.83 (0.71,
      0.97)] specifically among male births (males: n = 1047; females: n = 988).
      Dietary intake of >70% of energy from carbohydrate was also associated with
      increased risk (AOR: 1.67; 95% CI: 1.00, 2.78), whereas >25% of energy from fat
      intake was associated with decreased risk (AOR: 0.61; 95% CI: 0.41, 0.90) of SGA
      in male births. Conclusions: Higher carbohydrate and lower fat intakes early in
      pregnancy were associated with increased risk of male SGA births. Therefore, we
      speculate that fetal sex acts as a modifier of the role of maternal
      periconceptional nutrition in optimal fetoplacental growth.

PMID- 30239559
TI  - Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative
      lipid targets, non-HDL cholesterol and apolipoprotein B: a systematic review and
      meta-analysis of randomized controlled trials.
AB  - Background: Studies have identified viscous dietary fiber as potentially
      attenuating cholesterol, including psyllium, which reduces LDL cholesterol and
      thus may complement cardiovascular disease (CVD) treatment. Objectives: The aims
      of this study were to update evidence on the effect of psyllium on LDL
      cholesterol and to provide an assessment of its impact on alternate markers: non
      HDL cholesterol and apolipoprotein B (apoB). Design: Medline, EMBASE, CINAHL, and
      the Cochrane Central Register of Controlled Trials were searched through 3
      October 2017. Independent reviewers extracted relevant data and assessed risk of
      bias. We included randomized controlled trials with a duration of >=3 wk that
      assessed the effect of psyllium on blood lipids in individuals with or without
      hypercholesterolemia. Data were pooled by using the generic inverse variance
      method with random-effects models and expressed as mean differences (MDs) with
      95% CIs. Heterogeneity was assessed by Cochran's Q statistic and quantified by
      the I2 statistic. Overall quality of the evidence was assessed by using the GRADE
      (Grading of Recommendations Assessment, Development, and Evaluation) approach.
      Results: We included 28 trials in our analysis (n = 1924). Supplementation of a
      median dose of ~10.2 g psyllium significantly reduced LDL cholesterol (MD = -0.33
      mmol/L; 95% CI: -0.38, -0.27 mmol/L; P < 0.00001), non-HDL cholesterol (MD = 
      0.39 mmol/L; 95% CI: -0.50, -0.27 mmol/L; P < 0.00001), and apoB (MD = -0.05 g/L;
      95% CI: -0.08, -0.03 g/L; P < 0.0001). Effect estimates for LDL cholesterol and
      non-HDL cholesterol were graded as moderate quality on the basis of downgrades
      for inconsistency and graded as high quality for apoB. Conclusion: Psyllium fiber
      effectively improves conventional and alternative lipids markers, potentially
      delaying the process of atherosclerosis-associated CVD risk in those with or
      without hypercholesterolemia. This trial is registered at www.clinicaltrials.gov
      as NCT03346733.

PMID- 30239560
TI  - LncRNA-HOTAIR inhibition aggravates oxidative stress-induced H9c2 cells injury
      through suppression of MMP2 by miR-125.
AB  - Acute myocardial infarction (AMI) is one of the major causes of morbidity and
      mortality in the world. Ischemia/reperfusion (I/R) injury-induced cardiomyocytes
      death is the main obstacle that limits the heart function recovery of the AMI
      patients. Reactive oxygen species (ROS) generated by mitochondria is the main
      pathological stimulus of cardiomyocytes death during heart I/R injury process.
      Hence, to understand the underlying mechanism of cardioymocytes proliferation and
      apoptosis under oxidative stress is crucial for effective AMI therapy. In this
      study, we found that the expression of long non-coding RNA HOTAIR was
      significantly downregulated in H9c2 cells in response to oxidative stimuli.
      HOTAIR knockdown further attenuated H9c2 cells proliferation and accelerated H9c2
      cells apoptosis in oxidative stress, while HOTAIR overexpression can protect H9c2
      cells from oxidative stress-induced injury. Additionally, HOTAIR acted as a
      sponge for miR-125. MiR-125 inhibitors restored the H9c2 cells proliferation and
      migration potential after HOTAIR knockdown in oxidative stress. Meanwhile, MMP2
      was identified as a target of miR-125. MMP2 knockdown blocked miR-125 inhibitors'
      protect effect on H9c2 cells in oxidative stress. Further study demonstrated that
      HOTAIR inhibition can aggravate oxidative stress-induced H9c2 cells injury
      through HOTAIR/miR-125/MMP2 axis. Our finding revealed a novel regulatory
      mechanism for cardiomyocytes proliferation and apoptosis under oxidative stress
      conditions, which provided a therapeutic approach for myocardium repair after AMI
      injury.

PMID- 30239561
TI  - Effects of 3-hydroxybutyrate and free fatty acids on muscle protein kinetics and
      signaling during LPS-induced inflammation in humans: anticatabolic impact of
      ketone bodies.
AB  - Background: Acute inflammation, and subsequent release of bacterial products
      (e.g. LPS), inflammatory cytokines, and stress hormones, is catabolic, and the
      loss of lean body mass predicts morbidity and mortality. Lipid intermediates may
      reduce protein loss, but the roles of free fatty acids (FFAs) and ketone bodies
      during acute inflammation are unclear. Objective: We aimed to test whether
      infusions of 3-hydroxybutyrate (3OHB), FFAs, and saline reduce protein catabolism
      during exposure to LPS and Acipimox (to restrict and control endogenous
      lipolysis). Design: A total of 10 healthy male subjects were randomly tested 3
      times, with: 1) LPS, Acipimox (Olbetam) and saline, 2) LPS, Acipimox, and
      nonesterified fatty acids (Intralipid), and 3) LPS, Acipimox, and 3OHB, during a
      5-h basal period and a 2-h hyperinsulinemic, euglycemic clamp. Labeled
      phenylalanine, tyrosine, and urea tracers were used to estimate protein kinetics,
      and muscle biopsies were taken for Western blot analysis of protein metabolic
      signaling. Results: 3OHB infusion increased 3OHB concentrations (P < 0.0005) to
      3.5 mM and decreased whole-body phenylalanine-to-tyrosine degradation. Basal and
      insulin-stimulated net forearm phenylalanine release decreased by >70% (P <
      0.005), with both appearance and phenylalanine disappearance being profoundly
      decreased. Phosphorylation of eukaryotic initiation factor 2alpha at Ser51 was
      increased in skeletal muscle, and S6 kinase phosphorylation at Ser235/236 tended
      (P = 0.074) to be decreased with 3OHB infusion (suggesting inhibition of protein
      synthesis), whereas no detectable effects were seen on markers of protein
      breakdown. Lipid infusion did not affect phenylalanine kinetics, and insulin
      sensitivity was unaffected by interventions. Conclusion: During acute
      inflammation, 3OHB has potent anticatabolic actions in muscle and at the whole
      body level; in muscle, reduction of protein breakdown overrides inhibition of
      synthesis. This trial was registered at clinicaltrials.gov as NCT01752348.

PMID- 30239562
TI  - The Psychological Experience of Awaiting Breast Diagnosis.
AB  - Background: Each year, over 1 million women in the USA undergo diagnostic breast
      biopsies, many of which culminate in a benign outcome. However, for many
      patients, the experience of awaiting biopsy results is far from benign, instead
      provoking high levels of distress. Purpose: To take a multifaceted approach to
      understanding the psychological experience of patients undergoing a breast
      biopsy. Method: Female patients (N = 214) were interviewed at an appointment for
      a breast biopsy, just prior to undergoing the biopsy procedure. Pertinent to the
      current investigation, the interview assessed various patient characteristics,
      subjective health and cancer history, support availability, outcome expectations,
      distress, and coping strategies. Results: The findings revealed a complex set of
      interrelationships among patient characteristics, markers of distress, and use of
      coping strategies. Patients who were more distressed engaged in more avoidant
      coping strategies. Regarding the correlates of distress and coping, subjective
      health was more strongly associated with distress and coping than was cancer
      history; perceptions of support availability were also reliably associated with
      distress. Conclusion: Taken together, the results suggest that patients focus on
      their immediate experience (e.g., subjective health, feelings of risk,
      perceptions of support) in the face of the acute moment of uncertainty prompted
      by a biopsy procedure, relative to more distal considerations such as cancer
      history and demographic characteristics. These findings can guide clinicians'
      interactions with patients at the biopsy appointment and can serve as a
      foundation for interventions designed to reduce distress in this context.

PMID- 30239557
TI  - Dietary Antioxidants, Circulating Antioxidant Concentrations, Total Antioxidant
      Capacity, and Risk of All-Cause Mortality: A Systematic Review and Dose-Response
      Meta-Analysis of Prospective Observational Studies.
AB  - The associations of various dietary or circulating antioxidants with the risk of
      all-cause mortality in the general population have not been established yet. A
      systematic search was performed in PubMed and Scopus, from their inception up to
      October 2017. Prospective observational studies reporting risk estimates of all
      cause mortality in relation to dietary intake and/or circulating concentrations
      of antioxidants were included. Random-effects meta-analyses were conducted. Forty
      one prospective observational studies (total n = 507,251) involving 73,965 cases
      of all-cause mortality were included. The RRs of all-cause mortality for the
      highest compared with the lowest category of circulating antioxidant
      concentrations were as follows: total carotenes, 0.60 (95% CI: 0.46, 0.74);
      vitamin C, 0.61 (95% CI: 0.53, 0.69); selenium, 0.62 (95% CI: 0.45, 0.79); beta
      carotene, 0.63 (95% CI: 0.57, 0.70); alpha-carotene, 0.68 (95% CI: 0.58, 0.78);
      total carotenoids, 0.68 (95% CI: 0.56, 0.80); lycopene, 0.75 (95% CI: 0.54,
      0.97); and alpha-tocopherol, 0.84 (95% CI: 0.77, 0.91). The RRs for dietary
      intakes were: total carotenoids, 0.76 (95% CI: 0.66, 0.85); total antioxidant
      capacity, 0.77 (95% CI: 0.73, 0.81); selenium, 0.79 (95% CI: 0.73, 0.85); alpha
      carotene, 0.79 (95% CI: 0.63, 0.94); beta-carotene, 0.82 (95% CI: 0.77, 0.86);
      vitamin C, 0.88 (95% CI: 0.83, 0.94); and total carotenes, 0.89 (95% CI: 0.81,
      0.97). A nonsignificant inverse association was found for dietary zinc,
      zeaxanthin, lutein, and vitamin E. The nonlinear dose-response meta-analyses
      demonstrated a linear inverse association in the analyses of dietary beta
      carotene and total antioxidant capacity, as well as in the analyses of
      circulating alpha-carotene, beta-carotene, selenium, vitamin C, and total
      carotenoids. The association appeared to be U-shaped in the analyses of serum
      lycopene and dietary vitamin C. The present study indicates that adherence to a
      diet with high antioxidant properties may reduce the risk of all-cause mortality.
      Our results confirm current recommendations that promote higher intake of
      antioxidant-rich foods such as fruit and vegetables.

PMID- 30239564
TI  - Corrigendum.

PMID- 30239563
TI  - Enhancing Behavior Change Technique Coding Methods: Identifying Behavioral
      Targets and Delivery Styles in Smoking Cessation Trials.
AB  - Background: The behavior change technique (BCT) taxonomy v1 is often used in
      systematic reviews for identifying active components of interventions. Its
      utility could be enhanced by linking BCTs to specific target behaviors and
      qualifying BCT delivery style. Purpose: To determine whether behavioral targets
      and delivery styles of BCTs can be coded reliably and to determine the utility of
      coding these characteristics. Methods: As part of a large systematic review of
      142 smoking cessation trials, two researchers independently coded publicly and
      privately held intervention and comparator group materials, specifying the
      behavioral target (quitting, abstinence, medication adherence, or treatment
      engagement) and delivery style (tailored vs. not tailored; active participation
      vs. passive receipt) of each BCT. Results: Researchers coded 3,843 BCTs, which
      were reliably attributed to behavioral targets (AC1 = 0.92, PABAK = 0.91).
      Tailoring (AC1 = 0.80, PABAK = 0.74) and participation (AC1 = 0.71, PABAK = 0.64)
      were also coded reliably. There was considerable variability between groups in
      quitting and abstinence BCTs (ranges: 0-41; 0-18) and in tailoring and
      participation (ranges: 0-20; 0-32), but less variability for medication adherence
      and treatment engagement (ranges: 0-6; 0-7). Conclusions: Behavioral targets and
      delivery styles of BCTs can be reliably identified and occur with sufficient
      frequency in smoking cessation trials for inclusion in quantitative syntheses
      (e.g., meta-regression analyses). Systematic reviewers could consider adopting
      these methods to evaluate the impact of intervention components targeting
      different behaviors, as well as the benefits of different BCT delivery styles.

PMID- 30239565
TI  - The physiologic and phenotypic significance of variation in human amylase gene
      copy number.
AB  - Background: Salivary alpha-amylase gene (AMY1) copy number (CN) correlates with
      the amount of salivary alpha-amylase, but beyond this, the physiologic
      significance is uncertain. Objective: We hypothesized that individuals with
      higher AMY1 CN would digest starchy foods faster and show higher postprandial
      responses and lower breath hydrogen excretion compared with those with low CN.
      Design: Four linked studies were conducted. In Study 1, we genotyped 201 healthy
      subjects with the use of real-time quantitative polymerase chain reaction and
      determined glucose tolerance, insulin sensitivity, salivary alpha-amylase
      activity, body mass index (BMI), and macronutrient intake. In Study 2, a pool of
      114 subjects tested 6 starchy foods, 3 sugary foods, 1 mixed meal, and 2
      reference glucose solutions, containing either 50 or 25 g of available
      carbohydrate. In Study 3, we compared glycemic and insulin responses to starchy
      foods with responses to glucose in 40 individuals at extremes of high and low CN.
      In Study 4, we compared breath hydrogen and methane responses over 8 h in 30
      individuals at extremes of CN. Results: AMY1 CN correlated positively with
      salivary alpha-amylase activity (r = 0.62, P < 0.0001, n = 201) but not with BMI,
      glucose tolerance, or insulin sensitivity. However, CN was strongly correlated
      with normalized glycemic responses to all starchy foods (explaining 26-61% of
      interindividual variation), but not to sucrose or fruit. Individuals in the
      highest compared with the lowest decile of CN produced modestly higher glycemia
      (+15%, P = 0.018), but not insulinemia, after consuming 2 starchy foods. Low-CN
      individuals displayed >6-fold higher breath methane levels in the fasting state
      and after starch ingestion than high-CN individuals (P = 0.001), whereas hydrogen
      excretion was similar. Conclusions: Starchy foods are digested faster and produce
      higher postprandial glycemia in individuals with high AMY1 CN. In contrast,
      having low CN is associated with colonic methane production. This trial was
      registered at www.anzctr.org.au as ACTRN12617000670370.

PMID- 30239566
TI  - RNApuzzler: Efficient Outerplanar Drawing of RNA-Secondary Structures.
AB  - Motivation: RNA secondary structure is a useful representation for studying the
      function of RNA, which captures most of the free energy of RNA folding. Using
      empirically determined energy parameters, secondary structures of nucleic acids
      can be efficiently computed by recursive algorithms. Several software packages
      supporting this task are readily available. As RNA secondary structures are
      outerplanar graphs, they can be drawn without intersection in the plane.
      Interpretation by the practitioner is eased when these drawings conform to a
      series of additional constraints beyond outerplanarity. These constraints are the
      reason why RNA drawing is difficult. Many RNA drawing algorithms therefore do not
      always produce intersection-free (outerplanar) drawings. Results: To remedy this
      shortcoming, we propose here the RNApuzzler algorithm, which is guaranteed to
      produce intersection-free drawings. It is based on a drawing algorithm respecting
      constraints based on nucleotide distances (RNAturtle). We investigate relaxations
      of these constraints allowing for intersection-free drawings. Based on these
      relaxations, we implemented a fully automated, simple, and robust algorithm that
      produces aesthetic drawings adhering to previously established guidelines. We
      tested our algorithm using the RFAM database and found that we can compute
      intersection-free drawings of all RNAs therein efficiently. Availability and
      Implementation: The software can be accessed freely at:
      https://github.com/dwiegreffe/RNApuzzler. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30239567
TI  - The Encyclopedia of Proteome Dynamics: The KinoViewer.
AB  - Summary: The Encyclopedia of Proteome Dynamics (EPD) 'KinoViewer' is an
      interactive data visualisation tool designed for analysis and exploration of both
      protein and transcript data, showing expression of kinase genes in either Human
      or Mouse cells and tissues. The KinoViewer provides a comprehensive, updated
      graphical display of all human/mouse kinases and an open access analysis tool for
      the community with a user-friendly graphical interface. Availability and
      Implementation: The KinoViewer is based on a manually drawn SVG, which is
      utilised with D3.js to create a dynamic visualisation. It can be accessed at:
      https://peptracker.com/epd/analytics/. The KinoViewer is currently only
      accessible through the EPD, it is open access and can be used either to view
      internal datasets, or used to upload and visualise external user datasets.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 30239568
TI  - Whole-Body Vibration and Trunk Posture During Operation of Agricultural
      Machinery.
AB  - Exposure to whole-body vibration (WBV) is common among agricultural workers and
      is associated with musculoskeletal health outcomes such as low back pain. Little
      is known, however, about the characteristics of exposure experienced during
      actual production practices. We measured WBV levels during agricultural machinery
      use among a sample of farmers (n = 55) performing routine agricultural activities
      and explored machinery attributes that may explain WBV summary measures. We also
      measured trunk posture to provide additional information about physical exposures
      during machinery operation. Measurements were made on-farm and during actual work
      conditions of a sample of agricultural machines (n = 112), including tractors,
      combines, heavy utility vehicles, and all-terrain vehicles (ATVs). Results
      indicated the presence of high levels of vibration (median frequency-weighted
      root-mean-square acceleration of approximately 0.8 m s-2) with time signatures
      that include high-amplitude mechanical shocks (median crest factor of nearly 23).
      Compared to other machinery types, combines exhibited the lowest WBV levels and
      among the most favorable trunk postures. Substantial variability was observed in
      both the WBV and trunk posture summary measures, suggesting for future studies
      that alternative sampling strategies are needed to fully capture temporal
      patterns of machinery use.

PMID- 30239569
TI  - Detection of Herpes Simplex Virus and Varicella-Zoster Virus by Traditional and
      Multiplex Molecular Methods.
AB  - Objectives: To compare multiplex nucleic acid amplification tests (NAATs) that
      detect and differentiate herpes simplex virus (HSV) and varicella-zoster virus
      (VZV) with traditional virologic assays. Methods: The HSV ELVIS Test System
      (Quidel, San Diego, CA) and/or Light Diagnostics VZV direct fluorescent antibody
      (DFA) kit (Millipore Sigma, Billerica, MA), as well as an ARIES HSV 1&2/VZV assay
      (Luminex, Austin, TX) and the Solana HSV1 + 2/VZV Assay (Quidel), were performed
      on non-cerebrospinal fluid specimens. Results: The sensitivities/specificities
      for the ELVIS, Aries, and Solana assays for HSV were 71.1%/93.2%, 94.9%/93.2%,
      and 94.7%/100%, respectively. The sensitivities/specificities for the DFA, Aries,
      and Solana assays for VZV were 71.4%/100%, 100%/96.0%, and 95.3%/100%,
      respectively. HSV and VZV were detected but clinically unsuspected in 5.4% and
      4.2% of the specimens, respectively. Conclusions: Both NAAT assays were
      comparable and more sensitive than traditional methods. The recovery of
      unsuspected HSV and VZV from clinical specimens supports the implementation of a
      combined HSV/VZV assay.

PMID- 30239570
TI  - Strategies for calibrating models of biology.
AB  - Computational and mathematical modelling has become a valuable tool for
      investigating biological systems. Modelling enables prediction of how biological
      components interact to deliver system-level properties and extrapolation of
      biological system performance to contexts and experimental conditions where this
      is unknown. A model's value hinges on knowing that it faithfully represents the
      biology under the contexts of use, or clearly ascertaining otherwise and thus
      motivating further model refinement. These qualities are evaluated through
      calibration, typically formulated as identifying model parameter values that
      align model and biological behaviours as measured through a metric applied to
      both. Calibration is critical to modelling but is often underappreciated. A
      failure to appropriately calibrate risks unrepresentative models that generate
      erroneous insights. Here, we review a suite of strategies to more rigorously
      challenge a model's representation of a biological system. All are motivated by
      features of biological systems, and illustrative examples are drawn from the
      modelling literature. We examine the calibration of a model against distributions
      of biological behaviours or outcomes, not only average values. We argue for
      calibration even where model parameter values are experimentally ascertained. We
      explore how single metrics can be non-distinguishing for complex systems, with
      multiple-component dynamic and interaction configurations giving rise to the same
      metric output. Under these conditions, calibration is insufficiently constraining
      and the model non-identifiable: multiple solutions to the calibration problem
      exist. We draw an analogy to curve fitting and argue that calibrating a
      biological model against a single experiment or context is akin to curve fitting
      against a single data point. Though useful for communicating model results, we
      explore how metrics that quantify heavily emergent properties may not be suitable
      for use in calibration. Lastly, we consider the role of sensitivity and
      uncertainty analysis in calibration and the interpretation of model results. Our
      goal in this manuscript is to encourage a deeper consideration of calibration,
      and how to increase its capacity to either deliver faithful models or demonstrate
      them otherwise.

PMID- 30239571
TI  - Interpretation and potential biases of Mendelian randomization estimates with
      time-varying exposures.
AB  - Mendelian randomization (MR) is used to answer a variety of epidemiologic
      questions. One stated advantage of MR is that it estimates a "lifetime effect" of
      exposure though this term remains vaguely-defined. Instrumental variable
      analysis, on which MR is based, has focused on estimating the effects of point or
      time-fixed exposures rather than "lifetime effects". We use an empirical example
      with data from the Rotterdam Study to demonstrate how confusion can arise when
      estimating "lifetime effects". We provide one possible definition of a lifetime
      effect: the average change in outcome measured at time t when the entire exposure
      trajectory from conception to time t is shifted by one unit. We show that MR only
      estimates this type of lifetime effect under specific conditions, for example
      when the effect of the genetic variants used on exposure do not change over time
      (which many genetic variants commonly used in MR do). Lastly, we simulate the
      magnitude of bias that would result in realistic scenarios that use genetic
      variants with effects that change over time. We recommend future MR studies
      carefully consider the effect of interest and how genetic variants whose effects
      change with time may impact the interpretability and validity of their results.

PMID- 30239572
TI  - Development, Implementation, and Evaluation of a Fourth-Year Medical School
      Elective Course in Blood Banking and Transfusion Medicine.
AB  - Objectives: Knowledge of transfusion medicine by medical students is limited.
      Transfusion medicine physicians developed, implemented, and evaluated a half-day
      elective on transfusion medicine for fourth-year medical students. Methods: The
      course included a didactic lecture with integrated audience response questions
      and role-playing, as well as a "Jeopardy"-style game to review the material. The
      same 10-question knowledge quiz was administered before and after the elective.
      Results: Both knowledge quizzes were taken by 102 students. An average score of
      3.3 was obtained on the initial quiz, with only three (3%) students having a
      passing score (>=6 correct questions). The average score after the elective was
      6.6, with 83 (81%) students having a passing score. Students found the elective
      was informative (62 students, 60.8%), very useful (56, 54.9%), and practical (51,
      50%), although some thought it was challenging (22, 21.6%). Conclusions: A short
      course for medical students that allowed repetition of concepts using several
      teaching modalities improved their knowledge in transfusion medicine.

PMID- 30239573
TI  - Are You on the Right Platform? A Conjoint Analysis of Social Media Preferences in
      Aesthetic Surgery Patients.
AB  - Background: Social media has become an indispensable tool for patients to learn
      about aesthetic surgery. Currently, procedure-specific patient preferences for
      social media platforms and content are unknown. Objectives: To evaluate social
      media preferences of patients seeking aesthetic surgery. Methods: We utilized a
      choice-based conjoint analysis survey to analyze the preferences of patients
      seeking three common aesthetic procedures - breast augmentation (BA), facial
      rejuvenation (FR) and combined breast/abdominal surgery (BAB). Participants were
      asked to choose among social media platforms (Facebook, Twitter, Instagram,
      Snapchat, Pinterest, Tumblr, YouTube), information extent (basic, moderate,
      comprehensive), delivery mechanism (pre-recorded video, live-video, photographs,
      text description), messenger (surgeon, nurse/clinic staff, patient) and option
      for interactivity (Yes/No). The survey was administered using an Internet
      crowdsourcing service (Amazon Mechanical Turk(c)). Results: A total of 647
      participants were recruited: 201 in BA, 255 in FR and 191 in BAB. Amongst
      attributes surveyed, participants in all three groups (BA, FR, BAB) valued social
      media platform as the most important (30.9%, 33.1%, 31.4%), followed by
      information extent (23.1%, 22.9%, 21.6%), delivery mechanism (18.9%, 17.4%, 18%),
      messenger (16%, 17%, 17.2%) and interactivity (11.1%, 9.8%, 11.8%). Within these
      attributes, Facebook ranked as the preferred platform, with comprehensive
      information extent, live-video as the delivery mechanism and surgeon as the
      messenger as most preferred. Conclusion: The choice of social media platform is
      the most important factor for patients, with a preference for comprehensive
      information delivered by the surgeon via live-video on Facebook. Our study
      elucidates social media usage in common aesthetic populations, which can help
      improve aesthetic patient outreach.

PMID- 30239574
TI  - A Clustering Linear Combination Approach to Jointly Analyze Multiple Phenotypes
      for GWAS.
AB  - Summary: There is an increasing interest in joint analysis of multiple phenotypes
      for genome-wide association studies (GWASs) based on the following reasons.
      First, cohorts usually collect multiple phenotypes and complex diseases are
      usually measured by multiple correlated intermediate phenotypes. Second, jointly
      analyzing multiple phenotypes may increase statistical power for detecting
      genetic variants associated with complex diseases. Third, there is increasing
      evidence showing that pleiotropy is a widespread phenomenon in complex diseases.
      In this paper, we develop a clustering linear combination (CLC) method to jointly
      analyze multiple phenotypes for GWASs. In the CLC method, we first cluster
      individual statistics into positively correlated clusters and then, combine the
      individual statistics linearly within each cluster and combine the between
      cluster terms in a quadratic form. CLC is not only robust to different signs of
      the means of individual statistics, but also reduce the degrees of freedom of the
      test statistic. We also theoretically prove that if we can cluster the individual
      statistics correctly, CLC is the most powerful test among all tests with certain
      quadratic forms. Our simulation results show that CLC is either the most powerful
      test or has similar power to the most powerful test among the tests we compared,
      and CLC is much more powerful than other tests when effect sizes align with
      inferred clusters. We also evaluate the performance of CLC through a real case
      study. Availability: R code for implementing our method is available at
      http://www.math.mtu.edu/~shuzhang/software.html. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30239575
TI  - A Prospective Study of Dairy Food Intake and Early Menopause.
AB  - Early natural menopause, the cessation of ovarian function prior to age 45,
      affects ~10% of women and increases risk of cardiovascular disease and other
      conditions. Laboratory evidence suggests a potential role of dairy foods in the
      ovarian aging process; however, no prior epidemiologic studies have evaluated how
      dairy intake is associated with risk of early menopause. We therefore evaluated
      how intakes of total, low-fat, high-fat and individual dairy foods are associated
      with early menopause in the Nurses' Health Study II. Women who were premenopausal
      at the start of follow-up in 1991 were followed until 2011 for early menopause.
      Food frequency questionnaires were used to assess dietary intake. In Cox
      proportional hazards models adjusting for age, smoking, and other factors, total
      baseline dairy intake of >=4 servings/day versus <4 servings/week was associated
      with 23% lower risk of early menopause (95% confidence interval (CI): 0.64, 0.93;
      P-trend = 0.08). Associations appeared to be limited to low-fat dairy foods (>=2
      servings/day versus <3 servings/month HR: 0.83; 95% CI: 0.68, 1.01; P-trend =
      0.02), whereas high-fat dairy intake was not associated with early menopause. Low
      fat dairy foods may represent a modifiable risk factor to reduce risk of early
      menopause among premenopausal women.

PMID- 30239576
TI  - Human endogenous retroviruses and their implication for immunotherapeutics of
      cancer.
AB  - Human endogenous retroviruses (HERVs) have recently caught increased attention as
      a potential internal trigger to sensitize tumor cells to immunotherapies. HERVs
      are remnants of retroviral germline infections that resulted in chromosomal
      integration into all the cells of the progeny. Today, HERVs constitute ~8% of the
      human genome, but most elements are highly degenerated, under strict epigenetic
      regulation, and rarely expressed in healthy tissues. However, cancer cells are
      specifically prone to reactivate the expression of HERV elements due to
      epigenetic dysregulation that accumulate during malignant transformation and when
      using epigenetic therapies. HERV expression can induce an interferon response due
      to induction of the viral defense pathway, so-called 'viral mimicry'. By
      mimicking viral infections, HERVs could function as an 'intrinsic adjuvant',
      possibly sensitizing cancer cells to immunological recognition. Furthermore,
      translated HERV elements may in themselves form a valuable pool of tumor
      associated antigens. Epitopes derived from HERVs have been recognized by
      cytotoxic CD8+ T cells, leading to cancer cell recognition. The combination of
      'viral mimicry' and T-cell recognition could provide a powerful combination with
      existing immune stimulatory therapies, such as checkpoint inhibition. This
      combination is currently being evaluated in clinical trials in a large number of
      cancers.

PMID- 30239577
TI  - Control principles for complex biological networks.
AB  - Networks have been widely used to model the structure of various biological
      systems. Currently, a series of approaches have been developed to construct
      reliable biological networks. However, the ultimate understanding of a biological
      system is to steer its states to the desired ones by imposing signals. The
      control process is dominated by the intrinsic structure and the dynamic
      propagation. To understand the underlying mechanisms behind the life process, the
      control theory can be applied to biological networks with specific target
      requirements. In this article, we first introduce the structural controllability
      of complex networks and discuss its advantages and disadvantages. Then, we review
      the effective control to meet the specific requirements for complex biological
      networks. Moreover, we summarize the existing methods for finding the unique
      minimum set of driver nodes via the optimal control for complex networks.
      Finally, we discuss the relationships between biological networks and structural
      controllability, effective control and optimal control. Moreover, potential
      applications of general control principles are pointed out.

PMID- 30239578
TI  - Alcohol Intake and Colorectal Cancer Risk in the Multiethnic Cohort Study.
AB  - To investigate the association of alcohol intake with colorectal cancer risk by
      race/ethnicity as well as sex, lifestyle-related factors, alcoholic beverage
      type, and anatomical subsite, we analyzed data from 190,698 African Americans,
      Native Hawaiians, Japanese Americans, Latinos and whites in the Multiethnic
      Cohort Study, with 4,923 incident cases during a 16.7-year follow-up period (1993
      2013). In multivariate Cox regression models, the hazard ratio (HR) was 1.16 (95%
      confidence interval (CI): 1.01, 1.34) for 15.0-29.9 g/day of alcohol and 1.28
      (95% CI: 1.12, 1.45) for >=30.0 g/day in men, and 1.06 (95% CI: 0.85, 1.32) and
      1.15 (95% CI: 0.92, 1.43), respectively, in women, compared with nondrinkers (P
      for heterogeneity by sex = 0.74). An increased risk was apparent in Native
      Hawaiians, Japanese Americans, Latinos and whites, and in individuals with body
      mass index <25.0 kg/m2, never use of nonsteroidal anti-inflammatory drugs, and
      lower intake of dietary fiber and folate. Beer and wine, but not liquor,
      consumption was positively related to colorectal cancer risk. The association was
      stronger for rectum and left colon than right colon tumors. Our findings suggest
      that the positive association between alcohol and colorectal cancer varies by
      race/ethnicity, lifestyle factors, alcoholic beverage type, and anatomical
      subsite of tumors.

PMID- 30239579
TI  - Commentary on: Does Stromal Vascular Fraction Ensure a Higher Survival in
      Autologous Fat Grafting for Breast Augmentation? A Volumetric Study Using 3
      Dimensional Laser Scanning.

PMID- 30239581
TI  - Revealing tumor heterogeneity of breast cancer by utilizing the linkage between
      somatic and germline mutations.
AB  - The intra-tumor heterogeneity is associated with cancer progression and
      therapeutic resistance, such as in breast cancer. While the existing methods for
      studying tumor heterogeneity only analyze variant allele frequency (VAF), the
      genotype of variant is also informative for inferring subclones, which can be
      detected by long reads or paired-end reads. We developed GenoClone to integrate
      VAF with the genotype of variant innovatively, so it showed superior performance
      of inferring the number of subclones, estimating the fractions of subclones and
      identifying somatic single-nucleotide variants composition of subclones. When
      GenoClone was applied to 389 TCGA breast cancer samples, it revealed extensive
      intra-tumor heterogeneity. We further found that a few somatic mutations were
      relevant to the late stage of tumor evolution, including the ones at the oncogene
      PIK3CA and the tumor suppress gene TP53. Moreover, 52 subclones that were
      identified from 167 samples shared high similarity of somatic mutations, which
      were clustered into three groups with the sizes of 24, 14 and 14. It is helpful
      for understanding the development of breast cancer in certain subgroups of people
      and the drug development for population level. Furthermore, GenoClone also
      identified the tumor heterogeneity in different aliquots of the same samples. The
      implementation of GenoClone is available at
      http://www.healthcare.uiowa.edu/labs/au/GenoClone/.

PMID- 30239580
TI  - Use and Reliability of Exposure Assessment Methods in Occupational Case-Control
      Studies in the General Population: Past, Present, and Future.
AB  - Introduction: Retrospective occupational exposure assessment has been challenging
      in case-control studies in the general population. We aimed to review (i) trends
      of different assessment methods used in the last 40 years and (ii) evidence of
      reliability for various assessment methods. Methods: Two separate literature
      reviews were conducted. We first reviewed all general population cancer case
      control studies published from 1975 to 2016 to summarize the exposure assessment
      approach used. For the second review, we systematically reviewed evidence of
      reliability for all methods observed in the first review. Results: Among the 299
      studies included in the first review, the most frequently used assessment methods
      were self-report/assessment (n = 143 studies), case-by-case expert assessment (n
      = 139), and job-exposure matrices (JEMs; n = 82). Usage trends for these methods
      remained relatively stable throughout the last four decades. Other approaches,
      such as the application of algorithms linking questionnaire responses to expert
      assigned exposure estimates and modelling of exposure with historical measurement
      data, appeared in 21 studies that were published after 2000. The second review
      retrieved 34 comparison studies examining methodological reliability. Overall, we
      observed slightly higher median kappa agreement between exposure estimates from
      different expert assessors (~0.6) than between expert estimates and exposure
      estimates from self-reports (~0.5) or JEMs (~0.4). However, reported reliability
      measures were highly variable for different methods and agents. Limited evidence
      also indicates newer methods, such as assessment using algorithms and measurement
      calibrated quantitative JEMs, may be as reliable as traditional methods.
      Conclusion: The majority of current research assesses exposures in the population
      with similar methods as studies did decades ago. Though there is evidence for the
      development of newer approaches, more concerted effort is needed to better adopt
      exposure assessment methods with more transparency, reliability, and efficiency.

PMID- 30239583
TI  - Validity of the Body Adiposity Index in Predicting Body Fat in Adults: A
      Systematic Review.
AB  - The Body Adiposity Index (BAI) is a practical anthropometric method used to
      measure body fat (BF) percentage (BF%). Recently developed, the validity and
      precision of BAI has been studied with adult samples of men and women,
      populations from different countries and ethnicities, varying amounts of BF, and
      sensitivity to detecting change over time. However, it is still necessary to
      determine its potential use in clinical practice and epidemiologic studies. Thus,
      our objective was to verify, through a systematic review, the validity of the BAI
      in predicting BF% in adults. Two independent researchers performed a search using
      PubMed, Web of Science, Science Direct, and Scopus databases. In order to be
      included, the studies had to use dual-energy X-ray absorptiometry (DXA) as a
      reference method. We excluded studies with samples from individuals with diseases
      or syndromes that alter the regional distribution of BF%. We included 19 studies
      with samples on individuals from different continents, varied ethnicities, both
      sexes, and a wide age range (18-83 y). The concordance of the BAI with DXA
      assessed by Lin's concordance correlation coefficient showed results classified
      as poor (pc < 0.90). Bland-Altman plots showed that the BAI produced large
      individual errors when predicting BF% in all studies using this analysis. The
      studies were consistent in affirming that the BAI showed limited capacity to
      estimate BF% in adults. The BAI shows wide individual errors, in agreement with
      the reference method, and a lack of sensitivity in detecting change in BF% over
      time. The method presents a systematic error of BF% overestimation in individuals
      with <=20% of BF, and underestimation in individuals with >30% of BF, regardless
      of sex, age, and ethnicity. The results of this systematic review show enough
      evidence that the BAI does not present satisfying results, and its use is not
      recommended for BF% determination in adults.

PMID- 30239582
TI  - Use of Stable Isotopes to Evaluate Bioefficacy of Provitamin A Carotenoids,
      Vitamin A Status, and Bioavailability of Iron and Zinc.
AB  - The ability of nutrition scientists to measure the status, bioavailability, and
      bioefficacy of micronutrients is affected by lack of access to the parts of the
      body through which a nutrient may travel before appearing in accessible body
      compartments (typically blood or urine). Stable isotope-labeled tracers function
      as safe, nonradioactive tools to follow micronutrients in a quantitative manner
      because the absorption, distribution, metabolism, and excretion of the tracer are
      assumed to be similar to the unlabeled vitamin or mineral. The International
      Atomic Energy Agency (IAEA) supports research on the safe use of stable isotopes
      in global health and nutrition. This review focuses on IAEA's contributions to
      vitamin A, iron, and zinc research. These micronutrients are specifically
      targeted by the WHO because of their importance in health and worldwide
      prevalence of deficiency. These 3 micronutrients are included in food
      fortification and biofortification efforts in low- and middle-income regions of
      the world. Vitamin A isotopic techniques can be used to evaluate the efficacy and
      effectiveness of interventions. For example, total body retinol stores were
      estimated by using 13C2-retinol isotope dilution before and after feeding Zambian
      children maize biofortified with beta-carotene to determine if vitamin A reserves
      were improved by the intervention. Stable isotopes of iron and zinc have been
      used to determine mineral bioavailability. In Thailand, ferrous sulfate was
      better absorbed from fish sauce than was ferrous lactate or ferric ammonium
      citrate, determined with the use of different iron isotopes in each compound.
      Comparisons of one zinc isotope injected intravenously with another isotope taken
      orally from a micronutrient powder proved that the powder increased total
      absorbed zinc from a meal in Pakistani infants. Capacity building by the IAEA
      with appropriate collaborations in low- and middle-income countries to use stable
      isotopes has resulted in many advancements in human nutrition.

PMID- 30239586
TI  - Alectinib as first-line therapy for ALK-rearranged NSCLC: A no-brainer?

PMID- 30239585
TI  - Early Vascular Aging Risk Assessment From Ambulatory Blood Pressure Monitoring:
      The Early Vascular Aging Ambulatory Score.
AB  - BACKGROUND: This study compared the diagnostic accuracy of blood pressure (BP)
      measurement methods, office BP, ambulatory BP monitoring (ABPM), and home BP, in
      the identification of early vascular aging (EVA) and developed a score to predict
      the risk of EVA in hypertensive patients. METHODS: Two-hundred eighty-two
      consecutive subjects (39.7% male) aged 56.8  +/-  15.8 years were included.
      Office and out-of-office BP measurements including ABPM on a usual working day
      and 7 days home BP monitoring were performed. Carotid-femoral pulse wave velocity
      (c-f PWV) was measured in all patients. EVA was defined as c-f PWV values higher
      than the expected for age average values according to European population data.
      RESULTS: In univariate analysis, EVA was significantly correlated with office
      systolic BP, average 24-hour systolic and diastolic BP, and average 24-hour and
      office heart rates. The area under the curve for predicting EVA was 0.624 (95% CI
      0.551 to 0.697), 0.559 (95% CI 0.484 to 0.635) and 0.565 (95% CI 0.49 to 0.641),
      for daytime, home, and office systolic BP, respectively. Ambulatory BP variables,
      age, sex, body mass index, diabetes mellitus (yes/no), and estimated glomerular
      filtration rate were used to develop a new score for EVA providing a total
      accuracy of 0.82, 0.84 sensitivity, and 0.78 specificity. CONCLUSIONS: In
      conclusion, the new risk score, Early Vascular Aging Ambulatory score, may
      accurately identify hypertensive patients with EVA using ABPM values and classic
      cardiovascular risk factors.

PMID- 30239587
TI  - Sequence clustering in bioinformatics: an empirical study.
AB  - Sequence clustering is a basic bioinformatics task that is attracting renewed
      attention with the development of metagenomics and microbiomics. The latest
      sequencing techniques have decreased costs and as a result, massive amounts of
      DNA/RNA sequences are being produced. The challenge is to cluster the sequence
      data using stable, quick and accurate methods. For microbiome sequencing data,
      16S ribosomal RNA operational taxonomic units are typically used. However, there
      is often a gap between algorithm developers and bioinformatics users. Different
      software tools can produce diverse results and users can find them difficult to
      analyze. Understanding the different clustering mechanisms is crucial to
      understanding the results that they produce. In this review, we selected several
      popular clustering tools, briefly explained the key computing principles,
      analyzed their characters and compared them using two independent benchmark
      datasets. Our aim is to assist bioinformatics users in employing suitable
      clustering tools effectively to analyze big sequencing data. Related data, codes
      and software tools were accessible at the link
      http://lab.malab.cn/~lg/clustering/.

PMID- 30239588
TI  - Integrating hypertension phenotype and genotype with hybrid non-negative matrix
      factorization.
AB  - Motivation: Hypertension is a heterogeneous syndrome in need of improved
      subtyping using phenotypic and genetic measurements with the goal of identifying
      subtypes of patients who share similar pathophysiologic mechanisms and may
      respond more uniformly to targeted treatments. Existing machine learning
      approaches often face challenges in integrating phenotype and genotype
      information and presenting to clinicians an interpretable model. We aim to
      provide informed patient stratification based on phenotype and genotype features.
      Results: In this article, we present a Hybrid Non-negative Matrix Factorization
      (HNMF) method to integrate phenotype and genotype information for patient
      stratification. HNMF simultaneously approximates the phenotypic and genetic
      feature matrices using different appropriate loss functions, and generates
      patient subtypes, phenotypic groups and genetic groups. Unlike previous methods,
      HNMF approximates phenotypic matrix under Frobenius loss, and genetic matrix
      under Kullback-Leibler (KL) loss. We propose an alternating projected gradient
      method to solve the approximation problem. Simulation shows HNMF converges fast
      and accurately to the true factor matrices. On a real-world clinical dataset, we
      used the patient factor matrix as features and examined the association of these
      features with indices of cardiac mechanics. We compared HNMF with six different
      models using phenotype or genotype features alone, with or without NMF, or using
      joint NMF with only one type of loss. HNMF significantly outperforms all
      comparison models. HNMF also reveals intuitive phenotype-genotype interactions
      that characterize cardiac abnormalities. Availability: Our code will be made
      publicly available on github upon publication. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30239584
TI  - Mathematical Optimization to Explore Tomorrow's Sustainable Diets: A Narrative
      Review.
AB  - A sustainable diet is, by definition, nutritionally adequate, economically
      affordable, culturally acceptable, and environmentally respectful. Designing such
      a diet has to integrate different dimensions of diet sustainability that may not
      be compatible with each other. Among multicriteria assessment methods, diet
      optimization is a whole-diet approach that simultaneously combines several
      metrics for dimensions of diet sustainability. This narrative review based on 67
      published studies shows how mathematical diet optimization can help with
      understanding the relations between the different dimensions of diet
      sustainability and how it can be properly used to identify sustainable diets.
      Diet optimization aims to find the optimal combination of foods for a population,
      a subpopulation, or an individual that fulfills a set of constraints while
      minimizing or maximizing an objective function. In the studies reviewed, diet
      optimization was used to examine the links between dimensions of diet
      sustainability, identify the minimum cost or environmental impact of a
      nutritionally adequate diet, or identify food combinations able to combine >=2
      sustainability dimensions. If some constraints prove difficult to fulfill, this
      signals an incompatibility between nutrient recommendations, over-monotonous food
      consumption patterns, an inadequate supply of nutrient-rich foods, or an
      incompatibility with other dimensions. If diet optimization proves successful, it
      can serve to design nutritionally adequate, culturally acceptable, economically
      affordable, and environmentally friendly diets. Diet optimization results can
      help define dietary recommendations, tackle food security issues, and promote
      sustainable dietary patterns. This review emphasizes the importance of carefully
      choosing the model parameters (variables, objective function, constraints) and
      input data and the need for appropriate expertise to correctly interpret and
      communicate the results. Future research should make improvements in the choice
      of metrics used to assess each aspect of a sustainable diet, especially the
      cultural dimension, to improve the practicability of the results.

PMID- 30239589
TI  - Maternal Smoking During Pregnancy and Timing of Puberty in Sons and Daughters: A
      Population-Based Cohort Study.
AB  - As early puberty has been linked to diseases later in life, identification of
      modifiable causes of early puberty is of interest. We explore the possible
      associations between maternal smoking during pregnancy and pubertal development
      in sons and daughters. Between 2012 and 2017, 15,819 children from the Danish
      National Birth Cohort, born during 2000-2003, provided half-yearly information on
      puberty from the age of 11 years. We estimated adjusted age differences (in
      months) at attaining various pubertal milestones, including Tanner stages, per 10
      daily cigarettes smoked in first trimester. In sons, smoking in pregnancy was
      associated with earlier genital development (Tanner 2: -1.3, 95% confidence
      interval (CI): -2.5, 0.0. Tanner 5: -3.7, 95% CI: -5.3, -2.0), pubic hair
      development (Tanner 2: -1.8, 95% CI: -2.9, -0.6. Tanner 5: -2.9, 95% CI: -4.2, 
      1.7), and voice break (-2.4, 95% CI: -3.6, -1.3). In daughters, smoking was
      associated with earlier breast development (Tanner 2: -3.4, 95% CI: -5.3, -1.5.
      Tanner 5: -4.7, 95% CI: -6.5, -2.9), pubic hair development stage 3 to 5 (Tanner
      5: -2.5, 95% CI: -4.1, -1.0), and menarche (-3.1, 95% CI: -4.0, -2.3). Fetal
      exposure to tobacco smoke may advance timing of puberty in boys and girls.

PMID- 30239591
TI  - Gimpute: An efficient genetic data imputation pipeline.
AB  - Motivation: Genotype imputation is essential for genome-wide association studies
      (GWAS) to retrieve information of untyped variants and facilitate comparability
      across studies. However, there is a lack of automated pipelines that perform all
      required processing steps prior to and following imputation. Results: Based on
      widely used and freely available tools, we have developed Gimpute, an automated
      processing and imputation pipeline for genome-wide association data. Gimpute
      includes processing steps for genotype liftOver, quality control, population
      outlier detection, haplotype pre-phasing, imputation, post imputation, data
      management and the extension to other existing pipeline. Availability: The
      Gimpute package is an open source R package and is freely available at
      https://github.com/transbioZI/Gimpute. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 30239590
TI  - Towards an eco-evolutionary understanding of endemism hotspots and refugia.
AB  - Background: Refugia are island-like habitats that are linked to long-term
      environmental stability and, as a result, high endemism. Conservation of refugia
      and endemism hotspots should be based on a deep ecological and evolutionary
      understanding of their functioning, which remains limited. Although functional
      traits can provide such insights, a corresponding, coherent framework is lacking.
      Proposed Framework: Plant communities in refugia and endemism hotspots should,
      due to long-term environmental stability, display unique functional
      characteristics linked to distinct phylogenetic patterns. Therefore, such
      communities should be characterized by a functional signature that exhibits: (1)
      distinct values and combinations of traits, (2) higher functional diversity and
      (3) a prevalence of similar traits belonging to more distantly related lineages
      inside, compared to outside, of endemism hotspots and refugia. While the limited
      functional trait data available from refugia and endemism hotspots do not allow
      these predictions to be tested rigorously, three potential applications of the
      functional signature in biogeography and conservation planning are highlighted.
      Firstly, it allows the functional characteristics of endemism hotspots and
      refugia to be identified. Secondly, the strength of the functional signature can
      be compared among these entities, and with the surrounding landscape, to provide
      an estimate of the capacity of endemism hotspots and refugia to buffer
      environmental changes. Finally, the pattern of the functional signature can
      reveal ecological and evolutionary processes driving community assembly and
      functioning, which can assist in predicting the effect of environmental changes
      (e.g. climate, land-use) on communities in endemism hotspots and refugia.
      Conclusion: The proposed functional signature concept allows the systematic
      integration of plant functional traits and phylogeny into the study of endemism
      hotspots and refugia, but more data on functional traits in these entities are
      urgently needed. Overcoming this limitation would facilitate rigorous testing of
      the proposed predictions for the functional signature, advancing the eco
      evolutionary understanding of endemism hotspots and refugia.

PMID- 30239592
TI  - Precision in 3-Dimensional Surface Imaging of the Face: A Handheld Scanner
      Comparison Performed in a Cadaveric Model.
AB  - Background: Handheld 3-dimensional surface imaging (3DSI) devices of various
      precision are becoming more versatile in their applications and more widely
      accepted by clinicians for documentation. Objectives: To compare the precision of
      facial volumetric change measurements of three 3DSI devices in the cadaveric
      model: Eva(r) (Artec 3D Inc., Luxembourg), Sense (r) (3D Systems, Rock Hill, SC,
      USA) and iSense(r) (3D Systems, Rock Hill, SC, USA). Methods: A total of 336
      scanning and analysis procedures were carried out in four cephalic specimens
      (mean age, 77.25 +/- 24.3 years; and mean BMI, 21.76 +/- 6.6 kg/m 2). Two
      superficial and two supraperiosteal regions of interest were injected with
      aliquots of 0.5 cc and subsequently scanned using the three different scanners.
      Correlation coefficients between the injected and the measured volume were
      computed. Results: The correlation coefficient for the Eva(r) scanner was for
      subcutaneous regions of interest rp=0.935 and for the supraperiosteal regions of
      interest rp=0.966, as compared to rp=0.760 and rp=0.364 (superficial vs.
      supraperiosteal) for the Sense (r) and rp=0.694 and rp=0.382 (superficial vs.
      supraperiosteal) for the iSense(r) scanner. Conclusions: 3DSI devices are capable
      of measuring surface volume changes of the face at a level of 0.5 cc surface
      volume change and can thus be regarded as useful tools in the pre-interventional,
      intra-interventional, and post-interventional phase of a treatment. One of the
      three evaluated scanners provided very high correlation coefficients between the
      injected and the measured volume (Eva(r)), whereas the other evaluated 3DSI
      devices provided moderate (Sense(r)) and low (iSense(r)) coefficients.

PMID- 30239594
TI  - Analysis and Comparison of Tissue-Marking Dye Detection via Light Microscopy,
      Telemicroscopy, and Virtual Microscopy.
AB  - Objectives: To examine the fidelity of ink color identification using light
      microscopy (LM), telemicroscopy (TM), and virtual microscopy (VM). Methods:
      Twenty H&E-stained frozen section slides, prepared after tissue inking with five
      stain combinations, were assessed by three pathologists using LM, TM, and VM. TM
      was performed using Mikroscan D2 slide scanner/LiveQ software with various
      objectives. VM was performed using Mikroscan D2 scanner/Qumulus software,
      specimens digitized at20*. Results: Sensitivity/specificity by LM was 100%/100%
      for all colors. TM showed high overall specificity but poor sensitivity,
      particularly red (54%). VM showed high specificity for all colors except black
      (69%) and, consequently, poor sensitivity for all colors except black (96%).
      Conclusions: TMD identification via telepathology showed loss of
      sensitivity/specificity vs LM and highlighted the need for caution when
      interpreting TMDs with digital technologies and the need for validation
      protocols.

PMID- 30239593
TI  - Evaluation of Dermal Exposure to the Herbicide Alachlor Among Vegetable Farmers
      in Thailand.
AB  - Vegetable farmers applying the herbicide alachlor may be highly exposed through
      dermal contact when spraying. Dermal patches were attached to 10 locations on the
      farmers' skin when they mixed and applied alachlor in vegetable farming areas in
      Thailand. Measurements were made on farmers using either a backpack sprayer with
      a 2 stroke gasoline motor and fan or a battery operated pump. Forty-seven
      vegetable farmers in Bungphra subdistrict of Thailand participated in this study.
      Both motorized and battery pump backpack sprayers wearing long-sleeve shirts had
      significantly lower alachlor concentrations on the dermal patches under their
      long-sleeve shirts compared to those who wore only short-sleeve shirts,
      regardless of the sprayer type. Moreover, sprayers wearing long pants had
      significantly lower alachlor concentrations on dermal patches placed under the
      pants on the lower legs than those wearing short pants, regardless of the sprayer
      type. The highest estimated alachlor exposures were found on the upper legs
      (median = 9.29 ug/h) for those using a 2 stroke engine/fan backpack sprayer and
      on the lower legs (2.87 ug/h) for those using the battery operated pump backpack
      sprayer. The estimated total body alachlor exposures of applicators using the 2
      stroke engine/fan backpack sprayer (219.48 ug/h) were significantly higher than
      those using the battery operated pump backpack sprayer (15.50 ug/h). Using long
      sleeve shirts as personal protection reduced alachlor exposures for the arms 97
      99% and wearing long pants reduced alachlor exposure to the legs for 81-99%.
      Thus, training about the protection provided by clothing choices would be one
      step in improving the health and safety of Thai farmers.

PMID- 30239595
TI  - The Origins and Early Evolution of Epidemiologic Research in Cardiovascular
      Diseases (CVD): A Tabular Record of Cohort and Case-Control Studies and
      Preventive Trials Initiated from 1946-1976.
AB  - This article provides a ready reference to the pioneering formal studies in CVD
      epidemiology during three decades of its evolution into an established academic
      field making contributions to the public health. The article is not intended to
      be a history of CVD epidemiology nor an editorial about its significance. The
      appended tables include the title and starting date of the early studies, the
      name of their principal investigator, and reference to a single defining article
      from each. The early observational studies of CVD epidemiology provided a widely
      useful CVD risk-factor paradigm. The early clinical trials justified the more
      definitive preventive trials of the 1980s and beyond. These early researches in
      populations, along with others in the clinic and laboratory, led to greater
      understanding of the causes of CVD, to a vigorous practice of preventive
      cardiology, and to national policy and programs of health promotion, all
      coincident with a 50-year decline in CVD mortality rates.

PMID- 30239596
TI  - Aesthetic Treatment Positively Impacts Social Perception: Analysis of Subjects
      From the HARMONY Study.
AB  - Background: The impact of facial aesthetic treatments not only enhances physical
      appearance, but also psychological well-being. Accordingly, patient-reported
      outcomes (PROs) are increasingly utilized as an important measure of treatment
      success. Observer-reported outcomes (OROs) are a relevant yet often-overlooked
      measure of treatment benefit. Objectives: The current study aimed to evaluate the
      impact of panfacial aesthetic treatment on the perception of an individual in a
      variety of social contexts. Methods: 2000 men and women (aged 18-65 years)
      participated in an online study designed to capture the blinded observer's social
      perception of pretreatment and posttreatment subjects who received panfacial
      aesthetic treatment in the HARMONY study. Perceptions relevant to character
      traits, age, attractiveness, and social status were evaluated. Observers were
      divided into 2 groups. Single Image Respondents (n=1500) viewed 6 single
      randomized subject images (3 pretreatment, 3 posttreatment) and Paired Image
      Respondents (n=500) viewed 6 pretreatment and posttreatment image pairs. Results:
      Single Image Respondents reported significantly (P <0.05) higher levels of
      agreement that posttreatment subjects appeared to possess more positive character
      traits (eg, healthy and approachable), were more socially adept, younger, more
      attractive, more successful at attracting others, and possessed a higher social
      status. Paired Image Respondents also reported a higher level of agreement
      posttreatment images were more aligned with positive character traits, younger
      and more attractive, and of a higher social status. Conclusions: The results
      suggest that the positive impact of minimally-invasive panfacial treatment
      extends beyond enhancing the physical appearance and highlights the importance of
      social perception and OROs in aesthetic medicine.

PMID- 30239597
TI  - An evaluation of supervised methods for identifying differentially methylated
      regions in Illumina methylation arrays.
AB  - Epigenome-wide association studies (EWASs) have become increasingly popular for
      studying DNA methylation (DNAm) variations in complex diseases. The Illumina
      methylation arrays provide an economical, high-throughput and comprehensive
      platform for measuring methylation status in EWASs. A number of software tools
      have been developed for identifying disease-associated differentially methylated
      regions (DMRs) in the epigenome. However, in practice, we found these tools
      typically had multiple parameter settings that needed to be specified and the
      performance of the software tools under different parameters was often unclear.
      To help users better understand and choose optimal parameter settings when using
      DNAm analysis tools, we conducted a comprehensive evaluation of 4 popular DMR
      analysis tools under 60 different parameter settings. In addition to evaluating
      power, precision, area under precision-recall curve, Matthews correlation
      coefficient, F1 score and type I error rate, we also compared several additional
      characteristics of the analysis results, including the size of the DMRs, overlap
      between the methods and execution time. The results showed that none of the
      software tools performed best under their default parameter settings, and power
      varied widely when parameters were changed. Overall, the precision of these
      software tools were good. In contrast, all methods lacked power when effect size
      was consistent but small. Across all simulation scenarios, comb-p consistently
      had the best sensitivity as well as good control of false-positive rate.

PMID- 30239598
TI  - Day-to-Day Home Blood Pressure Variability and Orthostatic Hypotension: The
      Nagahama Study.
AB  - BACKGROUND: The aim of this study is to clarify associations between orthostatic
      blood pressure (BP) change, as well as possible physiological factors, and day-to
      day home BP variability, a promising risk factor for cardiovascular outcomes.
      METHODS: Study participants were 6,465 community residents (age 58.3 years). Home
      BP was measured every morning and evening for 7 days. Orthostatic BP was
      calculated as the maximum difference between BP measured while sitting and
      remeasured after 1 and 3 minutes standing. RESULTS: Frequency of individuals who
      showed orthostatic BP decline was as follows: systolic BP (SBP) change >=-20 mm
      Hg: 2.6%, >=-10 mm Hg: 14.1%. These subgroups showed larger home SBP variability
      (average real variability: 11.3 +/- 5.3, 8.7 +/- 3.9 mm Hg) when compared with
      orthostatic normotensives (7.6 +/- 3.7 mm Hg) (all P < 0.001). Multiple linear
      regression analysis adjusted for major covariates, including seated BP,
      identified orthostatic BP drop as an independent determinant for morning BP
      variability (>=-20 mm Hg: beta = 0.037, P = 0.003; >=-10 mm Hg: beta = 0.026, P =
      0.036) but not for evening BP variability. Carotid hypertrophy was significantly
      associated with home BP variability (morning: beta = 0.052, P = 0.001; evening:
      beta = 0.065, P < 0.001) and showed a U-shaped association with orthostatic BP
      change. Plasma B-type natriuretic peptide level, a previously suggested factor
      for BP variability, did not show significant association with morning and evening
      BP variability. CONCLUSION: Orthostatic BP decline was significantly associated
      with morning BP variability. Large artery atherosclerosis was a common risk
      factor.

PMID- 30239600
TI  - Statistical Inference Relief (STIR) feature selection.
AB  - Motivation: Relief is a family of machine learning algorithms that uses nearest
      neighbors to select features whose association with an outcome may be due to
      epistasis or statistical interactions with other features in high-dimensional
      data. Relief-based estimators are non-parametric in the statistical sense that
      they do not have a parameterized model with an underlying probability
      distribution for the estimator, making it difficult to determine the statistical
      significance of Relief-based attribute estimates. Thus, a statistical inferential
      formalism is needed to avoid imposing arbitrary thresholds to select the most
      important features. Methods: We reconceptualize the Relief-based feature
      selection algorithm to create a new family of STatistical Inference Relief (STIR)
      estimators that retains the ability to identify interactions while incorporating
      sample variance of the nearest neighbor distances into the attribute importance
      estimation. This variance permits the calculation of statistical significance of
      features and adjustment for multiple testing of Relief-based scores.
      Specifically, we develop a pseudo t-test version of Relief-based algorithms for
      case-control data. Results: We demonstrate the statistical power and control of
      type I error of the STIR family of feature selection methods on a panel of
      simulated data that exhibits properties reflected in real gene expression data,
      including main effects and network interaction effects. We compare the
      performance of STIR when the adaptive radius method is used as the nearest
      neighbor constructor with STIR when the fixed-k nearest neighbor constructor is
      used. We apply STIR to real RNA-Seq data from a study of major depressive
      disorder and discuss STIR's straightforward extension to genome-wide association
      studies. Availability: Code and data available at
      http://insilico.utulsa.edu/software/STIR. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30239599
TI  - Rapid Molecular Diagnostics to Inform Empiric Use of Ceftazidime/Avibactam and
      Ceftolozane/Tazobactam against Pseudomonas aeruginosa: PRIMERS IV.
AB  - Background: Overcoming??-lactam resistance in pathogens such as Pseudomonas
      aeruginosa is a major clinical challenge. Rapid molecular diagnostics (RMDs) have
      the potential to inform selection of empiric therapy in patients infected by P.
      aeruginosa. Methods: In this study, we used a heterogeneous collection of 197 P.
      aeruginosa that included multidrug-resistant (MDR) isolates to investigate
      whether two representative RMDs (Acuitas Resistome Test and VERIGENE Gram
      Negative Blood Culture Test) could identify susceptibility to two newer ?
      lactam/?-lactamase inhibitor (BL-BLI) combinations, ceftazidime/avibactam (CZA)
      and ceftolozane/tazobactam (TOL/TAZO). Results: We found that the studied RMD
      platforms were able to correctly identify BL-BLI susceptibility [susceptibility
      sensitivity 100% (95% CI: 97%, 100%)] for both BL-BLIs. However, their ability to
      detect resistance to these BL-BLIs was lower [resistance sensitivity 66% (95% CI:
      52%, 78%) for TOL/TAZO and 33% (95% CI: 20%, 49%) for CZA]. Conclusions: The
      diagnostic platforms studied showed the most potential in scenarios where a
      resistance gene was detected or in scenarios where a resistance gene was not
      detected and the prevalence of resistance to TOL/TAZO or CZA is known to be low.
      Clinicians need to be mindful of the benefits and risks resulting from empiric
      treatment decisions based on resistance gene detection in P.aeruginosa,
      acknowledging that such decisions are impacted by the prevalence of resistance
      which varies temporally and geographically.

PMID- 30239601
TI  - Parkour LIMS: facilitating high-quality sample preparation in next generation.
AB  - Motivation: This paper presents Parkour, a software package for sample processing
      and quality management of next generation sequencing data and samples. Results:
      Starting with user requests, Parkour allows tracking and assessing samples based
      on predefined quality criteria through different stages of the sample preparation
      workflow. Ideally suited for academic core laboratories, the software aims to
      maximize efficiency and reduce turnaround time by intelligent sample grouping and
      a clear assignment of staff to work units. Tools for automated invoicing,
      interactive statistics on facility usage and simple report generation minimize
      administrative tasks. Provided as a web application, Parkour is a convenient tool
      for both deep sequencing service users and laboratory personal. A set of web APIs
      allow coordinated information sharing with local and remote bioinformaticians.
      The flexible structure allows workflow customization and simple addition of new
      features as well as the expansion to other domains. Availability: The code and
      documentation are available at https://github.com/maxplanck-ie/parkour.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 30239602
TI  - A modified case definition to facilitate essential hospital care during Ebola
      outbreaks.
AB  - During the late phase of the large West-African Ebola virus disease (EVD)
      outbreak, the majority of patients were cared for in designated treatment
      centers. However, the pre-existing health care infrastructure was overwhelmed
      with EVD in the first place. This had a huge impact on other, non-EVD related
      diseases, causing an un-preceded mounting of morbidity and mortality, which most
      likely exceeded the toll directly due to EVD. Consequently, one of the crucial
      questions is how to provide appropriate health care and safeguard functionality
      of a healthcare system also for all those patients not suspected or diagnosed to
      have EVD.We report here on the Lion Heart Medical Center experience in Sierra
      Leone and describe that a case definition broader than those commonly applied may
      be better suited in a scenario where it is of greater importance to identify
      atypically presenting, pauci-symptomatic cases.

PMID- 30239603
TI  - Holistic approach in patients with presumed Lyme borreliosis leads to less than
      10% of confirmation and more than 80% of antibiotics failure.
AB  - Background: There is no precise idea whether patients with chronic symptoms
      attributed to Lyme borreliosis (LB) have LB or another disease. Methods: We
      evaluated patients consulting for a presumed LB with a holistic approach
      including presumptive treatment. We included symptomatic patients who consulted
      with a presumed LB. They were classified as confirmed LB when they had four
      criteria, and possible LB if three with a positive clinical response to
      presumptive treatment. Results: Amongst the 301 patients, 275 (91%) were exposed
      to tick bites, and 165 (54%) were bitten by a tick. At presentation, 151 patients
      (50.1%) had already been treated with a median of one (1-22) course of
      antimicrobials, during 34 (28-730) days. The median number of symptoms was three
      (1-12) with a median duration of 16 (1 - 68) months. Median number of signs was
      zero (0 - 2). ELISA was positive in 84/295 (28.4%) for IgM and 86/295 (29.1%) for
      IgG, and immunoblot was positive in 21/191 (10.9%) for IgM and 50/191 (26.1 %)
      for IgG. Presumptive treatment after presentation failed in 46/88 patients (52%).
      Diagnosis of LB was confirmed in 29 patients (9.6%), and possible in 9 (2.9%). Of
      the 243 patients with non-LB diagnosis, diseases were psychological,
      musculoskeletal, neurological or other origin in 76 (31.2%), 48 (19.7%), 37
      (15.2%) and 82 (33.7%) patients respectively. Patients with other diseases were
      significantly younger, having more symptoms, a longest duration of symptoms, less
      clinical signs and less frequent LB positive serologies. Conclusion:
      Overdiagnosis and overtreatment of LB is worsening, and health authorities should
      investigate this phenomenon.

PMID- 30239604
TI  - Absence of NPR-C Attenuates TGF-beta1 Induced Selective Atrial Fibrosis and
      Atrial Fibrillation.
AB  - Aims: TGF-beta1 plays an important role in atrial fibrosis and atrial
      fibrillation (AF); previous studies have shown that the atria are more
      susceptible to TGF-beta1 mediated fibrosis than the ventricles. Natriuretic
      peptides play an important role in cardiac remodeling and fibrosis, but the role
      of natriuretic peptide clearance receptor (NPR-C) is largely unknown. We
      investigated the role of NPR-C in modulating TGF-beta1 signaling in the atria.
      Methods and results: MHC-TGF-beta1 transgenic mice (TGF-beta1-Tx), which develop
      isolated atrial fibrosis and AF, were cross-bred with NPR-C knock-out mice (NPR-C
      KO). Transverse aortic constriction (TAC) was performed in wild type and NPR-C
      knockout mice to study. atrial fibrosis and AF inducibility in a pathophysiologic
      model. Electrophysiology, molecular and histologic studies were performed in
      adult mice. siRNA was used to interrogate the interaction between TGF-beta1 and
      natriuretic peptide (NP) signaling pathways in isolated atrial and ventricular
      fibroblasts/myofibroblasts. NPR-C expression level was 17+/-5.8 fold higher in
      the atria compared to the ventricle in Wild type (Wt) mice (p = 0.009). Cross
      bred mice demonstrated markedly decreased pSmad2 and collagen expression, atrial
      fibrosis and AF compared to TGF-beta1-Tx mice with intact NPR-C. There was a
      marked reduction in atrial fibrosis gene expression and AF inducibility in the
      NPR-C-KO-TAC mice compared to Wt-TAC. In isolated fibroblasts, knockdown of NPR-C
      resulted in a marked reduction of pSmad2 (56%+/-4% and 24%+/-14% reduction in
      atrial and ventricular fibroblasts, respectively) and collagen (76%+/-15% and
      35%+/-23% reduction in atrial and ventricular fibroblasts/myofibroblasts,
      respectively) in response to TGF-beta1 stimulation. This effect was reversed by
      simultaneously knocking down NPR-A but not with simultaneous knock down of PKG-1.
      Conclusions: The differential response to TGF-beta1 stimulated fibrosis between
      the atria and ventricle are in part mediated by the abundance of NPR-C receptors
      in the atria.

PMID- 30239605
TI  - Chronic respiratory symptoms and lung abnormalities among people with a history
      of tuberculosis in Uganda: a national survey.
AB  - Background: People with pulmonary tuberculosis (TB) are at risk of developing
      chronic respiratory disorders due to residual lung damage. So far, the scope of
      the problem in high burden TB countries is relatively unknown. Methods: Chronic
      respiratory symptoms (cough and phlegm lasting >2 weeks) and radiological lung
      abnormalities were compared between adults with and without a history of TB among
      the general population of Uganda. Multivariable regression models were used to
      estimate odds ratios with adjustment for age, gender, smoking, education, setting
      and region. Random effects models accounted for village clustering effect.
      Results: Of 45,293 invited people from 70 villages, 41,154 (90.9%) participated
      in the survey. 798 had a history of TB and among them, 16% had respiratory
      symptoms and 41% x-ray abnormalities. Adjusted odds ratios showed strong evidence
      for individuals with a history of TB having increased risk of respiratory
      symptoms (OR=4.02, 95%CI: 3.25-4.96) and x-ray abnormalities (OR=17.52, 95%CI:
      14.76-20.79); attributing 6% and 24% of the respective population risks.
      Conclusions: In Uganda, a history of TB was a strong predictor of respiratory
      symptoms and lung abnormalities, before older age and smoking. Eliminating TB
      disease could reduce the prevalence of chronic respiratory symptoms as much as
      eliminating smoking.

PMID- 30239606
TI  - Powerful and efficient SNP-set association tests across multiple phenotypes using
      GWAS summary data.
AB  - Motivation: Many GWAS conducted in the past decade have identified tens of
      thousands of disease related variants, which in total explained only part of the
      heritability for most traits. There remain many more genetics variants with small
      effect sizes to be discovered. This has motivated the development of sequencing
      studies with larger sample sizes and increased resolution of genotyped variants,
      e.g., the ongoing NHLBI Trans-Omics for Precision Medicine (TOPMed) whole genome
      sequencing project. An alternative approach is the development of novel and more
      powerful statistical methods. The current dominating approach in the field of
      GWAS analysis is the "single trait single variant" association test, despite the
      fact that most GWAS are conducted in deeply-phenotyped cohorts with many
      correlated traits measured. In this paper, we aim to develop rigorous methods
      that integrate multiple correlated traits and multiple variants to improve the
      power to detect novel variants. In recognition of the difficulty of accessing raw
      genotype and phenotype data due to privacy and logistic concerns, we develop
      methods that are applicable to publicly available GWAS summary data. Results: We
      build rigorous statistical models for GWAS summary statistics to motivate novel
      multi-trait SNP-set association tests, including variance component test, burden
      test and their adaptive test, and develop efficient numerical algorithms to
      quickly compute their analytical p-values. We implement the proposed methods in
      an open source R package. We conduct thorough simulation studies to verify the
      proposed methods rigorously control type I errors at the genome-wide significance
      level, and further demonstrate their utility via comprehensive analysis of GWAS
      summary data for multiple lipids traits and glycemic traits. We identified many
      novel loci that were not detected by the individual trait based GWAS analysis.
      Availability: We have implemented the proposed methods in an R package freely
      available at http://www.github.com/baolinwu/MSKAT. Supplementary information:
      Supplementary materials provide more technical details and analysis results, and
      are available at Bioinformatics online.

PMID- 30239607
TI  - CINNA: An R/CRAN package to decipher Central Informative Nodes in Network
      Analysis.
AB  - Availability and implementation: CINNA is available in CRAN, including a
      tutorial. URL: https://cran.r-project.org/web/packages/CINNA/index.html.
      Supplementary information: Supplementary data are available online.

PMID- 30239608
TI  - Going for the Gold: A Description of 'Centers of Excellence' Designation by
      Infectious Diseases Society of America.
AB  - Antimicrobial stewardship programs (ASPs) are recommended by the Centers for
      Disease Control and Prevention and World Health Organization and mandated by The
      Joint Commission to curb antimicrobial resistance (AMR). However, < 50% of
      institutions have optimal ASPs in place. Building on its experience of
      antimicrobial stewardship (AMS) advocacy, Infectious Disease Society of America
      (IDSA) developed the AMS Centers of Excellence (CoE) program, which will serve as
      a conduit to share best practices and highlight the standards for other hospitals
      to strive to achieve to advance the field of AMS. A designation of CoE signifies
      that these institutions deliver high-quality care consistently, serve as the
      "gold" standard for executing novel AMS principles, and demonstrate commitment to
      their ASP. This paper describes the process and purpose of designating
      institutions as AMS CoEs, provides awareness to clinicians on opportunities
      available through IDSA with this CoE designation, and discusses the evolution of
      the program.

PMID- 30239609
TI  - A Case Control Study to Identify Community Venues Associated with Genetically
      Clustered Multidrug-Resistant Tuberculosis Disease in Lima, Peru.
AB  - Background: The majority of tuberculosis transmission occurs in community
      settings. The primary aim of this study was to assess the association between
      exposure to community venues and multidrug-resistant tuberculosis (MDR-TB)
      disease. The secondary aim was to describe the social networks of MDR-TB cases
      and controls. Methods: This case-control study was conducted in Lima, Peru. We
      recruited lab-confirmed MDR-TB cases and community controls matched on age and
      sex. Whole-genome sequencing was used to identify genetically-clustered cases.
      Venue-tracing interviews (nonblinded) were conducted to enumerate community
      venues frequented by participants. Logistic regression was used to assess the
      association between MDR-TB disease and person-time spent in community venues. A
      location-based social network was constructed with respondents connected if they
      reported frequenting the same venue and an exponential random graph model (ERGM)
      was fitted to model the network. Results: We enrolled 59 cases and 65 controls.
      Participants reported 729 unique venues. Mean number of venues reported was
      similar in both groups (P=0.92). Cases reported spending more person-time (hours)
      in healthcare and transportation venues than controls (P<0.05). Person-time in
      healthcare venues (Adjusted Odds Ratio (OR)=1.67, P=0.01), schools (OR=1.53,
      P<0.01), and transportation (OR=1.25, P=0.03) was associated with MDR-TB disease.
      Healthcare venues, markets, cinemas, and transportation venues were commonly
      shared among clustered cases. The ERGM indicated significant community
      segregation between cases and controls. Case networks were more densely
      connected. Conclusions: Exposure to healthcare venues, schools and transportation
      was associated with MDR-TB disease. Intervention across the segregated network of
      case venues may be necessary to effectively stem transmission.

PMID- 30239610
TI  - Plasma 25-hydroxyvitamin D and the Longitudinal Risk of Sepsis in the REGARDS
      Cohort.
AB  - Background: Low baseline plasma 25-hydroxyvitamin D (25(OH)D is associated with
      increased risk of acute respiratory infections, but its association with long
      term risk of sepsis remains unclear. Methods: Case-cohort analysis of
      participants selected from the Reasons for Geographic and Racial Differences in
      Stroke study (REGARDS), a US cohort of 30,239 adults >= 45 years old. We measured
      baseline plasma 25(OH)D in 711 sepsis cases and in 992 participants randomly
      selected from the REGARDS cohort. We captured sepsis events by screening records
      with International Classification of Disease methods then adjudicating clinical
      charts for significant, suspected infection and severe inflammatory response
      syndrome criteria on presentation. Results: In the study sample, the median age
      of participants was 65.0 years, 41% self-identified as black, and 45% were male.
      Mean plasma 25-hydroxyvitamin D concentration was 25.8 ng/ml with 31% of subjects
      < 20 ng/ml. The adjusted risk of community-acquired sepsis was higher for each
      lower category of baseline 25(OH)D. Specifically, in a Cox proportional hazards
      model adjusting for multiple potential confounders, when compared to a baseline
      25(OH)D >33.6 ng/ml, lower 25(OH)D groups were associated with higher hazards of
      sepsis (16.5-22.4 ng/ml hazard ratio 3.21, 95% confidence interval [CI] 1.98 to
      5.21; < 16.5 ng/ml hazard ratio 6.81, 95%CI 3.95 to 11.73). Results did not
      materially differ in analyses stratified by race or age. Conclusions: In the
      REGARDS cohort of community-dwelling US adults, low plasma 25(OH)D measured at a
      time of relative health was independently associated with increased risk of
      sepsis.

PMID- 30239613
TI  - Erratum.

PMID- 30239614
TI  - Sperm capacitation is associated with phosphorylation of the testis-specific
      radial spoke protein Rsph6a.
AB  - Mammalian sperm undergo a series of biochemical and physiological changes
      collectively known as capacitation in order to acquire the ability to fertilize.
      Although the increase in phosphorylation associated with mouse sperm capacitation
      is well established, the identity of the proteins involved in this signaling
      cascade remain largely unknown. Tandem mass spectrometry (MS/MS) has been used to
      identify the exact sites of phosphorylation and to compare the relative extent of
      phosphorylation at these sites. In the present work, we find that a novel site of
      phosphorylation on a peptide derived from the radial spoke protein Rsph6a is more
      phosphorylated in capacitated mouse sperm. The Rsph6a gene has six exons, five of
      which are conserved during evolution in flagellated cells. The exon containing
      the capacitation-induced phosphorylation site was found exclusively in eutherian
      mammals. Transcript analyses revealed at least two different testis-specific
      splicing variants for Rsph6a.Rsph6a mRNA expression was restricted to
      spermatocytes. Using antibodies generated against the Rsph6a N-terminal domain,
      Western blotting and immunofluorescence analyses indicated that the protein
      remains in mature sperm and localizes to the sperm flagellum. Consistent with its
      role in the axoneme, solubility analyses revealed that Rsph6 is attached to
      cytoskeletal structures. Based on previous studies in Chlamydomonas reinhardtii,
      we predict that Rsph6 participates in the interaction between the central pair of
      microtubules and the surrounding pairs. The findings that Rsph6a is more
      phosphorylated during capacitation and is predicted to function in axonemal
      localization make Rsph6a a candidate protein mediating signaling processes in the
      sperm flagellum.

PMID- 30239615
TI  - Association between duration of aminoglycoside treatment and outcome of cavitary
      Mycobacterium avium complex lung disease.
AB  - Background: Although aminoglycosides are recommended for cavitary Mycobacterium
      avium complex lung disease (MAC-LD), the optimal duration of treatment is
      unclear. We investigated the association between duration of aminoglycoside
      treatment and outcomes in cavitary MAC-LD. Methods: Among patients diagnosed with
      macrolide-susceptible cavitary MAC-LD between 2000 and 2013, 101 patients who
      received treatment up to August 2017 with a regimen containing aminoglycosides
      were enrolled at a tertiary referral center in South Korea. Their medical records
      were retrospectively reviewed. The duration of aminoglycoside treatment was at
      the discretion of the attending physician. Results: A total of 75 patients
      (74.3%) were administered aminoglycosides for >=3 months (median 164 days),
      whereas the remaining 26 patients (25.7%) received treatment for <3 months
      (median 59 days). The overall treatment success rate was 63.4% (64/101). Patients
      treated with aminoglycosides for >=3 months had a significantly higher success
      rate than those treated for <3 months (69.3% vs. 46.2%, P = 0.035). Multivariate
      analysis revealed that aminoglycoside treatment for >=3 months was a significant
      factor for treatment success (adjusted odds ratio [aOR], 3.602; 95% confidence
      interval [CI], 1.249-10.390; P = 0.018). Recurrence occurred in 8 (22.9%) of 35
      patients who were followed for at least 3 years after the end of treatment; all 8
      patients received aminoglycosides for >=3 months. Conclusion: Patients with
      cavitary MAC-LD treated with aminoglycosides for >=3 months showed higher
      treatment success rate than those treated for <3 months. However, treatment for
      >=3 months was not associated with the development of recurrence.

PMID- 30239612
TI  - UBA1/GARS-dependent pathways drive sensory-motor connectivity defects in spinal
      muscular atrophy.
AB  - Deafferentation of motor neurons as a result of defective sensory-motor
      connectivity is a critical early event in the pathogenesis of spinal muscular
      atrophy, but the underlying molecular pathways remain unknown. We show that
      restoration of ubiquitin-like modifier-activating enzyme 1 (UBA1) was sufficient
      to correct sensory-motor connectivity in the spinal cord of mice with spinal
      muscular atrophy. Aminoacyl-tRNA synthetases, including GARS, were identified as
      downstream targets of UBA1. Regulation of GARS by UBA1 occurred via a non
      canonical pathway independent of ubiquitylation. Dysregulation of UBA1/GARS
      pathways in spinal muscular atrophy mice disrupted sensory neuron fate,
      phenocopying GARS-dependent defects associated with Charcot-Marie-Tooth disease.
      Sensory neuron fate was corrected following restoration of UBA1 expression and
      UBA1/GARS pathways in spinal muscular atrophy mice. We conclude that defective
      sensory motor connectivity in spinal muscular atrophy results from perturbations
      in a UBA1/GARS pathway that modulates sensory neuron fate, thereby highlighting
      significant molecular and phenotypic overlap between spinal muscular atrophy and
      Charcot-Marie-Tooth disease.

PMID- 30239616
TI  - CPPred-FL: a sequence-based predictor for large-scale identification of cell
      penetrating peptides by feature representation learning.
AB  - Cell-penetrating peptides (CPPs) have been shown to be a transport vehicle for
      delivering cargoes into live cells, offering great potential as future
      therapeutics. It is essential to identify CPPs for better understanding of their
      functional mechanisms. Machine learning-based methods have recently emerged as a
      main approach for computational identification of CPPs. However, one of the main
      challenges and difficulties is to propose an effective feature representation
      model that sufficiently exploits the inner difference and relevance between CPPs
      and non-CPPs, in order to improve the predictive performance. In this paper, we
      have developed CPPred-FL, a powerful bioinformatics tool for fast, accurate and
      large-scale identification of CPPs. In our predictor, we introduce a new feature
      representation learning scheme that enables one to learn feature representations
      from totally 45 well-trained random forest models with multiple feature
      descriptors from different perspectives, such as compositional information,
      position-specific information and physicochemical properties, etc. We integrate
      class and probabilistic information into our feature representations. To improve
      the feature representation ability, we further remove redundant and irrelevant
      features by feature space optimization. Benchmarking experiments showed that
      CPPred-FL, using 19 informative features only, is able to achieve better
      performance than the state-of-the-art predictors. We anticipate that CPPred-FL
      will be a powerful tool for large-scale identification of CPPs, facilitating the
      characterization of their functional mechanisms and accelerating their
      applications in clinical therapy.

PMID- 30239611
TI  - White matter diffusion alterations precede symptom onset in autosomal dominant
      Alzheimer's disease.
AB  - White matter alterations are present in the majority of patients with Alzheimer's
      disease type dementia. However, the spatiotemporal pattern of white matter
      changes preceding dementia symptoms in Alzheimer's disease remains unclear,
      largely due to the inherent diagnostic uncertainty in the preclinical phase and
      increased risk of confounding age-related vascular disease and stroke in late
      onset Alzheimer's disease. In early-onset autosomal-dominantly inherited
      Alzheimer's disease, participants are destined to develop dementia, which
      provides the opportunity to assess brain changes years before the onset of
      symptoms, and in the absence of ageing-related vascular disease. Here, we
      assessed mean diffusivity alterations in the white matter in 64 mutation carriers
      compared to 45 non-carrier family non-carriers. Using tract-based spatial
      statistics, we mapped the interaction of mutation status by estimated years from
      symptom onset on mean diffusivity. For major atlas-derived fibre tracts, we
      determined the earliest time point at which abnormal mean diffusivity changes in
      the mutation carriers were detectable. Lastly, we assessed the association
      between mean diffusivity and cerebrospinal fluid biomarkers of amyloid, tau,
      phosphorylated-tau, and soluble TREM2, i.e. a marker of microglia activity.
      Results showed a significant interaction of mutations status by estimated years
      from symptom onset, i.e. a stronger increase of mean diffusivity, within the
      posterior parietal and medial frontal white matter in mutation carriers compared
      with non-carriers. The earliest increase of mean diffusivity was observed in the
      forceps major, forceps minor and long projecting fibres-many connecting default
      mode network regions-between 5 to 10 years before estimated symptom onset. Higher
      mean diffusivity in fibre tracts was associated with lower grey matter volume in
      the tracts' projection zones. Global mean diffusivity was correlated with lower
      cerebrospinal fluid levels of amyloid-beta1-42 but higher levels of tau,
      phosphorylated-tau and soluble TREM2. Together, these results suggest that
      regionally selective white matter degeneration occurs years before the estimated
      symptom onset. Such white matter alterations are associated with primary
      Alzheimer's disease pathology and microglia activity in the brain.

PMID- 30239617
TI  - G1 phase cell cycle arrest in NSCLC in response to LZ-106, an analog of enoxacin,
      is orchestrated through ROS overproduction in a P53-dependent manner.
AB  - LZ-106, a newly synthetized analog of quinolone, has been shown to be highly
      effective in NSCLC in both cultured cells and xenograft mouse model with low
      toxicity, yet the molecular mechanisms still requires exploration. Here, we
      substantiated the involvement of P53 activation in intracellular ROS generation
      upon LZ-106 treatment, and related P53 to the ROS-induced viability inhibition
      and apoptosis, which was exhibited in the previous research. P53 was shown to
      play an indispensable role in the elevated levels of intracellular ROS in LZ-106
      treated NSCLC cells through ROS detection. We further identified the anti
      proliferation effect of LZ-106 in NSCLC cells through G1 phase cell cycle arrest
      by cell cycle analysis, with the expression analysis of the key proteins, and
      discovered that the cell cycle arrest effect is also mediated by induction of ROS
      in a P53-dependent manner. In addition, the tumor suppression effect exhibited in
      vivo was demonstrated to be similar to that in vitro, which requires the
      participation of P53. Thus, LZ-106 is a potent antitumor drug possessing potent
      proliferation inhibition and apoptosis induction ability through the P53
      dependent ROS modulation both in vitro and in vivo.

PMID- 30239618
TI  - Evidence for peri-ictal blood-brain barrier dysfunction in patients with
      epilepsy.
AB  - Epilepsy has been associated with a dysfunction of the blood-brain barrier. While
      there is ample evidence that a dysfunction of the blood-brain barrier contributes
      to epileptogenesis, blood-brain barrier dysfunction as a consequence of single
      epileptic seizures has not been systematically investigated. We hypothesized that
      blood-brain barrier dysfunction is temporally and anatomically associated with
      epileptic seizures in patients and used a newly-established quantitative MRI
      protocol to test our hypothesis. Twenty-three patients with epilepsy undergoing
      inpatient monitoring as part of their presurgical evaluation were included in
      this study (10 females, mean age +/- standard deviation: 28.78 +/- 8.45). For
      each patient, we acquired quantitative T1 relaxation time maps (qT1) after both
      ictal and interictal injection of gadolinium-based contrast agent. The postictal
      enhancement of contrast agent was quantified by subtracting postictal qT1 from
      interictal qT1 and the resulting DeltaqT1 was used as a surrogate imaging marker
      of peri-ictal blood-brain barrier dysfunction. Additionally, the serum
      concentrations of MMP9 and S100, both considered biomarkers of blood-brain
      barrier dysfunction, were assessed in serum samples obtained prior to and after
      the index seizure. Fifteen patients exhibited secondarily generalized tonic
      clonic seizures and eight patients exhibited focal seizures at ictal injection of
      contrast agent. By comparing DeltaqT1 of the generalized tonic-clonic seizures
      and focal seizures groups, the anatomical association between ictal epileptic
      activity and postictal enhancement of contrast agent could be probed. The
      generalized tonic-clonic seizures group showed significantly higher DeltaqT1 in
      the whole brain as compared to the focal seizures group. Specific analysis of
      scans acquired later than 3 h after the onset of the seizure revealed higher
      DeltaqT1 in the generalized tonic-clonic seizures group as compared to the focal
      seizures group, which was strictly lateralized to the hemisphere of seizure
      onset. Both MMP9 and S100 showed a significantly increased postictal
      concentration. The current study provides evidence for the occurrence of a blood
      brain barrier dysfunction, which is temporally and anatomically associated with
      epileptic seizures. qT1 after ictal contrast agent injection is rendered as
      valuable imaging marker of seizure-associated blood-brain barrier dysfunction and
      may be measured hours after the seizure. The observation of the strong anatomical
      association of peri-ictal blood-brain barrier dysfunction may spark the
      development of new functional imaging modalities for the post hoc visualization
      of brain areas affected by the seizure.

PMID- 30239619
TI  - Lack of APC somatic mutation is associated with early-onset colorectal cancer in
      African Americans.
AB  - African Americans (AAs) have higher incidence and mortality rates of colorectal
      cancer (CRC) compared to other US populations. They present with more right
      sided, microsatellite stable disease and are diagnosed at earlier ages compared
      to non-Hispanic whites (NHWs). To gain insight into these trends, we conducted
      exome sequencing (n=45), copy number (n=33), and methylation analysis (n=11) of
      microsatellite stable AA CRCs. Results were compared to data from The Cancer
      Genome Atlas (TCGA). Two of the 45 tumors contained POLE mutations. In the
      remaining 43 tumors, only 27 (63%) contained loss-of-function mutations in APC
      compared to 80% of TCGA NHW CRCs. APC mutation-negative CRCs were associated with
      an earlier onset of CRC (p=0.01) and with previous cancer (p=0.06). They were
      also associated with lower overall mutation burden, fewer copy number variants,
      and a DNA methylation signature that was distinct from the CpG island methylator
      phenotype characterized in microsatellite unstable disease. Three of the APC
      mutation-negative CRCs had loss-of-function mutations in BCL9L. Mutations in
      driver genes identified by TCGA exome analysis were less frequent in AA
      colorectal cancer cases than TCGA NHWs. Genes that regulate the WNT signaling
      pathway, including SOX9, GATA6, TET1, GLIS1, and FAT1, were differentially
      hypermethylated in APC mutation-negative CRCs, suggesting a novel mechanism for
      cancer development in these tumors. In summary, we have identified a subtype of
      CRC that is associated with younger age of diagnosis, lack of APC mutation,
      microsatellite and chromosome stability, lower mutation burden, and distinctive
      methylation changes.

PMID- 30239620
TI  - Randomized Controlled Trial of a Mobile Health Intervention to Promote Retention
      and Adherence to Pre-exposure Prophylaxis among Young People at Risk for Human
      Immunodeficiency Virus: The EPIC Study.
AB  - Background: Young men who have sex with men (MSM) are among the most vulnerable
      to HIV infection in the United States. While pre-exposure prophylaxis (PrEP) has
      demonstrated effectiveness, adherence and retention in care have been low among
      youth. Methods: We conducted a randomized controlled trial to evaluate the impact
      of a youth-tailored, bi-directional text-messaging PrEP support intervention
      (PrEPmate) on study retention and PrEP adherence. Young individuals at risk for
      HIV acquisition initiating PrEP within Chicago's safety-net hospital system were
      randomized 2:1 to receive PrEPmate or standard of care (SoC) for 36 weeks. The
      primary retention outcome was study-visit completion, and the primary adherence
      outcome was tenofovir diphosphate (TFV-DP) concentrations >=700 fmol/punch
      (consistent with >=4 doses/week) assessed at 4, 12, 24, and 36 weeks. The impact
      of PrEPmate on retention and adherence was evaluated using generalized estimating
      equation logistic models with robust standard errors. Results: From April 2015 to
      March 2016, 121 participants enrolled (mean age 24; 27% Black, 36% Latino).
      Across all visits, participants who received PrEPmate were more likely to attend
      study visits (86% PrEPmate vs. 71% SoC, OR=2.62, 95%CI 1.24-5.54) and have TFV-DP
      levels consistent with >=4 doses/week (72% PrEPmate vs. 57% SoC, OR=2.05, 95%CI
      1.06-3.94). PrEPmate efficacy did not differ significantly by age,
      race/ethnicity, education, or insurance. Overall, 88% reported PrEPmate to be
      very/somewhat helpful, and 92% would recommend PrEPmate to others. Conclusions:
      An interactive text-messaging intervention had high acceptability and
      significantly increased study-visit retention and PrEP adherence among young
      individuals at risk for HIV acquisition.

PMID- 30239621
TI  - Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised
      Children.
AB  - Background: Despite improved diagnostics, pulmonary pathogens in
      immunocompromised children frequently evade detection, leading to significant
      mortality. Therefore, we aimed to develop a highly sensitive metagenomic next
      generation sequencing assay capable of evaluating the pulmonary microbiome and
      identifying diverse pathogens in the lungs of immunocompromised children.
      Methods: We collected 41 lower respiratory specimens from 34 immunocompromised
      children undergoing evaluation for pulmonary disease at three children's
      hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel
      RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to
      the NCBI nucleotide reference database to determine taxonomic identities.
      Statistical outliers were determined based on abundance within each sample and
      relative to other samples in the cohort. Results: We identified a rich cross
      domain pulmonary microbiome containing bacteria, fungi, RNA viruses, and DNA
      viruses in each patient. Potentially pathogenic bacteria were ubiquitous among
      samples but could be distinguished as possible causes of disease by parsing for
      outlier organisms. Samples with bacterial outliers had significantly depressed
      alpha-diversity (median 0.61, IQR 0.33-0.72 vs. median 0.96, IQR 0.94-0.96,
      p<0.001). Potential pathogens were detected in half of samples previously
      negative by clinical diagnostics, demonstrating increased sensitivity for missed
      pulmonary pathogens (p<0.001). Conclusions: An optimized mNGS assay for pulmonary
      microbes demonstrates significant inoculation of the lower airways of
      immunocompromised children with diverse bacteria, fungi, and viruses. Potential
      pathogens can be identified based on absolute and relative abundance. Ongoing
      investigation is needed to determine the pathogenic significance of outlier
      microbes in the lungs of immunocompromised children with pulmonary disease.

PMID- 30239622
TI  - Increased relative abundance of Klebsiella pneumoniae carbapenemase-producing
      Klebsiella pneumoniae within the gut microbiota is associated with risk of
      bloodstream infection in long-term acute care hospital patients.
AB  - Background: An association between increased relative abundance of specific
      bacterial taxa in the intestinal microbiota and bacteremia has been reported in
      some high-risk patient populations. Methods: We collected weekly rectal swab
      samples from patients at one long-term acute care hospital (LTACH) in Chicago
      from May 2015 - May 2016. Samples were tested for Klebsiella pneumoniae
      carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) by PCR and culture.
      Positive samples underwent 16S rRNA gene sequence analysis; relative abundance of
      the operational taxonomic unit containing KPC-Kp was determined. Receiver
      operator characteristic (ROC) curves were constructed using results from analysis
      of the sample with highest relative abundance of KPC-Kp from each patient
      admission, excluding samples collected after KPC-Kp bacteremia. Cox regression
      analysis was performed to evaluate risk factors associated with time to achieve
      KPC-Kp relative abundance thresholds calculated by ROC curve analysis. Results:
      We collected 2,319 samples from 562 admissions (506 patients), of which 255
      (45.4%) were colonized with KPC-Kp and 11 (4.3%) had KPC-Kp bacteremia. By ROC
      curve analysis, relative abundance cutoff of 22% predicted KPC-Kp bacteremia with
      sensitivity 73%, specificity 72%, and relative risk 4.2 (P=0.01). In a
      multivariable Cox regression model adjusted for age, Charlson comorbidity index
      and medical devices, carbapenem receipt was associated with achieving the 22%
      relative abundance threshold (P=0.044). Conclusion: In adult LTACH patients,
      carbapenem receipt was associated with increased hazard for high relative
      abundance of KPC-Kp in the gut microbiota. Increased relative abundance of KPC-Kp
      was associated with KPC-Kp bacteremia. Whether bacteremia arose directly from
      bacterial translocation or indirectly from skin contamination followed by
      bloodstream invasion remains to be determined.

PMID- 30239623
TI  - Inhibition of TLR9-NF-kappaB-Mediated Sterile Inflammation Improves Pressure
      Overload-Induced Right Ventricular Dysfunction in Rats.
AB  - Aims: Recent accumulating evidence suggests that sterile inflammation plays a
      crucial role in the progression of various cardiovascular diseases. However, its
      contribution to right ventricular (RV) dysfunction remains unknown. The aim of
      the present study was to elucidate whether toll-like receptor 9 (TLR9)-NF-kappaB
      mediated sterile inflammation plays a critical role in the pathogenesis of RV
      dysfunction. Methods and results: We performed main pulmonary artery banding
      (PAB) in rats to induce RV pressure overload and dysfunction. On day 14 after
      PAB, the pressure overload impaired RV function as indicated by increased RV end
      diastolic pressure concomitant with macrophage infiltration and fibrosis, as well
      as maximal activation of NF-kappaB and TLR9. Short-term administration (days 14
      to 16 after PAB) of a specific TLR9 inhibitor, E6446, or an NF-kappaB inhibitor,
      pyrrolidine dithiocarbamate (PDTC) significantly attenuated NF-kappaB activation.
      Furthermore, long-term administration of E6446 (treatment: days 14 to 28) or PDTC
      (prevention: days -1 to 28; treatment: days 14 to 28) improved RV dysfunction
      associated with mitigated macrophage infiltration and fibrosis in RV and
      decreased serum BNP levels. Conclusions: Inhibition of TLR9-NF-kappaB pathway
      mediated sterile inflammation improved PAB-induced RV dysfunction in rats. This
      pathway plays a major role in the progression of pressure overload-induced RV
      dysfunction, and is potentially a novel therapeutic target for the disorder.

PMID- 30239624
TI  - Clinical effectiveness of influenza vaccination after allogeneic hematopoietic
      stem cell transplantation: A cross-sectional prospective observational study.
AB  - Background: Allogeneic hematopoietic stem cell recipients (allo-HSCT) are at high
      risk for morbidity and mortality from influenza respiratory virus infection
      (RVI). Vaccination is the primary method for preventing influenza RVI. Although
      the influenza vaccine is able to achieve serological response in some allo-HSCT
      recipients, its clinical benefit is still uncertain. Methods: In this prospective
      cross-sectional study, we retrospectively analyzed the effect of inactivated
      trivalent influenza vaccination status on the prevalence of influenza RVI in a
      consecutive cohort of 136 allo-HSCT adult recipients who developed 161 RVI over 5
      flu seasons (from 2013 to 2018). Respiratory virus in upper and/or lower
      respiratory tract specimens were tested using multiplex PCR panel assays.
      Results: Overall, we diagnosed 74 episodes (46%) of Influenza RVI in 70 allo-HSCT
      recipients. Influenza RVI occurred in 51% of the non-vaccinated compared to 36%
      of the vaccinated recipients (p= 0.036). Multivariate analysis showed that
      influenza vaccination was associated with lower prevalence of influenza RVI (OR
      0.39, p= 0.01). Multivariate risk factor analysis of lower respiratory tract
      disease (LRTD) identified two conditions associated with the probability of
      influenza RVI progression; influenza vaccination (OR 0.12, 95% C.I. 0.014-1, p=
      0.05) and high-risk immunodeficiency score index (OR 36, 95% C.I. 2.26-575, p=
      0.011). Influenza vaccination was also associated with lower likelihood of
      influenza-related hospital admission (14% vs 2%, p= 0.04). Conclusion: This study
      shows that influenza vaccination may have a clinical benefit in allo-HSCT
      recipients with virologicallly confirmed RVI, in terms of lower influenza RVI
      prevalence, LRTD progression and hospital admission.

PMID- 30239625
TI  - Embryonic stem cell-derived mmu-miR-291a-3p inhibits cellular senescence in human
      dermal fibroblasts through the TGF-?-receptor 2 pathway.
AB  - Senescent cells accumulate in various tissues over time, and contribute to tissue
      dysfunction and aging-associated phenotypes. Accumulating evidence suggests that
      cellular senescence can be inhibited through pharmacological intervention, as
      well as through treatment with soluble factors derived from embryonic stem cells
      (ESCs). In an attempt to investigate the anti-senescence factors secreted by
      ESCs, we analyzed mouse ESC-derived extracellular miRNAs in conditioned medium
      (CM) via miRNA array analysis. We selected mmu-miR-291a-3p as a putative anti
      senescence factor via bioinformatics analysis. We validated its inhibitory
      effects on replicative, adriamycin-induced, and ionizing radiation-induced
      senescence in human dermal fibroblasts. Treatment of senescent cells with mmu-miR
      291a-3p decreased senescence-associated-beta-galactosidase activity, enhanced
      proliferative potential, and reduced mRNA and protein expression of TGFBR2, p53,
      and p21. Mmu-miR-291a-3p in CM was enclosed in ESC-derived exosomes and exosomes
      purified from ESC-CM inhibited cellular senescence. The inhibitory effects of mmu
      miR-291a-3p were mediated through the TGFBR2 signaling pathway. Hsa-miR-371a-3p
      and hsa-miR-520e, the human homologs of mmu-miR-291a-3p, showed similar anti
      senescence activity. Furthermore, mmu-miR-291a-3p accelerated the excisional skin
      wound healing process in aged mice. Our results indicate that the ESC-derived mmu
      miR-291a-3p is a novel candidate agent that can be utilized for cell-free
      therapeutic intervention against aging and aging-related diseases.

PMID- 30239626
TI  - A molecular mechanism of nickel (II): reduction of nucleotide excision repair
      activity by structural and functional disruption of p53.

PMID- 30239627
TI  - Exploring sequence-based features for the improved prediction of DNA N4
      methylcytosine sites in multiple species.
AB  - Motivation: As one of important epigenetic modifications, DNA N4-methylcytosine
      (4mC) is recently shown to play crucial roles in restriction-modification
      systems. For better understanding of their functional mechanisms, it is
      fundamentally important to identify 4mC modification. Machine learning methods
      have recently emerged as an effective and efficient approach for the high
      throughput identification of 4mC sites, although high predictive error rates are
      still challenging for existing methods. Therefore, it is highly desirable to
      develop a computational method to more accurately identify m4C sites. Results: In
      this study, we propose a machine learning based predictor, namely 4mcPred-SVM,
      for the genome-wide detection of DNA 4mC sites. In this predictor, we present a
      new feature representation algorithm that sufficiently exploits sequence-based
      information. To improve the feature representation ability, we use a two-step
      feature optimization strategy, thereby obtaining the most representative
      features. Using the resulting features and Support Vector Machine (SVM), we
      adaptively train the optimal models for different species. Comparative results on
      benchmark datasets from six species indicate that our predictor is able to
      achieve generally better performance in predicting 4mC sites as compared to the
      state-of-the-art predictors. Importantly, the sequence-based features can
      reliably and robust predict 4mC sites, facilitating the discovery of potentially
      important sequence characteristics for the prediction of 4mC sites. Availability:
      The user-friendly webserver that implements the proposed 4mcPred-SVM is well
      established, and is freely accessible at http://server.malab.cn/4mcPred-SVM.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 30239628
TI  - Impact of Aging and HIV Infection on the Function of the C-Type Lectin Receptor
      MINCLE in Monocytes.
AB  - Both aging and HIV infection are associated with an enhanced pro-inflammatory
      environment that contributes to impaired immune responses and is mediated in part
      by innate immune pattern-recognition receptors. MINCLE is a C-type lectin
      receptor that recognizes trehalose 6,6,' di-mycolate (TDM) or "cord factor," the
      most abundant glycolipid in Mycobacterium tuberculosis (MTB). Here, we evaluated
      MINCLE function in monocytes in a cohort of HIV-infected and uninfected young (21
      35) and older adults (60 years) via stimulation of PBMCs with TDB (Trehalose-6,6
      dibehenate), a synthetic analog of TDM and measurement of cytokine production (IL
      10, IL-12, IL-6, TNF-) by multicolor flow cytometry. Our studies show an age- and
      HIV-associated increase in cytokine multi-functionality of monocytes both at the
      population and single cell level that was dominated by IL-12, IL-10 and IL-6.
      These findings provide insight into the host response to MTB, and possible
      sources for the pro-inflammatory environment seen in aging and HIV infection.

PMID- 30239629
TI  - Cost-effectiveness and Cost-utility of the Adherence Improving Self-management
      Strategy in Human Immunodeficiency Virus Care: A Trial-based Economic Evaluation.
AB  - Background: Several promising human immunodeficiency virus (HIV) treatment
      adherence interventions have been identified, but data about their cost
      effectiveness are lacking. This study examines the trial-based cost-effectiveness
      and cost-utility of the proven-effective Adherence Improving Self-Management
      Strategy (AIMS), from a societal perspective, with a 15-month time horizon.
      Methods: Treatment-naive and treatment-experienced patients at risk for viral
      rebound were randomized to treatment as usual (TAU) or AIMS in a multicenter
      randomized controlled trial in the Netherlands. AIMS is a nurse-led, 1-on-1 self
      management intervention incorporating feedback from electronic medication
      monitors, delivered during routine clinical visits. Main outcomes were costs per
      reduction in log10 viral load, treatment failure (2 consecutive detectable viral
      loads), and quality-adjusted life-years (QALYs). Results: Two hundred twenty
      three patients were randomized. From a societal perspective, AIMS was slightly
      more expensive than TAU but also more effective, resulting in an incremental cost
      effectiveness ratio (ICER) of ?549 per reduction in log10 viral load and ?1659
      per percentage decrease in treatment failure. In terms of QALYs, AIMS resulted in
      higher costs but more QALYs compared to TAU, which resulted in an ICER of ?27759
      per QALY gained. From a healthcare perspective, AIMS dominated TAU. Additional
      sensitivity analyses addressing key limitations of the base case analyses also
      suggested that AIMS dominates TAU. Conclusions: Base case analyses suggests that
      over a period of 15 months, AIMS may be costlier, but also more effective than
      TAU. All additional analyses suggest that AIMS is cheaper and more effective than
      TAU. This trial-based economic evaluation confirms and complements a model-based
      economic evaluation with a lifetime horizon showing that AIMS is cost-effective.

PMID- 30239630
TI  - Long-acting opioid use and the risk of serious infections: a retrospective cohort
      study.
AB  - Background: Although evidence from animal and human studies indicates opioid
      analgesics increase susceptibility to infections, it is unclear whether the risk
      varies by specific opioid. We compared the risk of serious infection among
      patients initiating long-acting opioid analgesics with and without previously
      reported immunosuppressive properties. Methods: We conducted a retrospective
      cohort study of Tennessee Medicaid enrollees age >=18 years initiating long
      acting opioids (1995-2015). Hospitalizations for serious infection were
      identified using validated coding algorithms. We used multivariable Poisson
      regression models to calculate adjusted incidence rate ratios (aIRR) and 95%
      confidence intervals (CI) to compare the risk of infection among patients using
      long-acting opioids with known immunosuppressive properties (morphine, fentanyl,
      methadone) to patients using long-acting opioids without immunosuppressive
      properties (oxycodone, oxymorphone, tramadol) accounting for demographics, opioid
      dose, comorbidities and pain conditions, medication use, frailty indicators and
      healthcare encounter history using exposure propensity scores. We further
      compared users of individual long-acting opioids to long-acting morphine users
      (considered the prototypical immunosuppressive opioid). Results: Among the 61240
      patients initiating opioids with immunosuppressive properties and 22811 patients
      initiating opioids without immunosuppressive properties, we identified 1906
      serious infections. Non-immunosuppressive opioid users had a lower rate of
      infections than immunosuppressive opioid users [aIRR:0.78 (95%CI:0.66-0.91)].
      Among individual opioids, oxycodone users had a lower rate of infection than
      morphine users [aIRR:0.73 (95%CI:0.61-0.89)]. There were no significant
      differences in the infection risk between other opioids and morphine. Conclusion:
      The risk of serious infections among long-acting opioid users varies by opioid
      type. Providers should carefully consider the risk of serious infections when
      making pain management decisions.

PMID- 30239632
TI  - Risk assessment for non-cardiac surgery after coronary stenting - keeping it
      simple.

PMID- 30239631
TI  - Asymptomatic Visceral Leishmania infantum Infection in U.S. Soldiers Deployed to
      Iraq.
AB  - Background: Visceral leishmaniasis (VL), due to Leishmania infantum, is a
      persistent intracellular parasitic infection transmitted by the bite of infected
      sand flies. Symptomatic VL has been reported in U.S. soldiers with Iraq
      deployment. Untreated symptomatic VL can be fatal; asymptomatic VL (AVL) may
      establish a lifelong risk of reactivation. We report prevalence and AVL risk
      factors in Operation Iraqi Freedom (OIF) deployers during 2002-11. Methods:
      Healthy soldiers exposed to VL endemic areas in Iraq and 50 controls who never
      traveled to endemic regions were recruited through military healthcare facilities
      (2015-17). Responses to a risk factor survey and blood samples were obtained.
      Leishmania research diagnostics utilized included ELISA, rk39 test strips,
      quantitative PCR, and interferon gamma release (IGRA) assays. Statistical
      analyses included Fisher's exact test, Pearson's Chi square test, Mann-Whitney U
      test, and logistic regression. Results: 200 deployed subjects were enrolled,
      mostly males (84.0%), of white ethnicity (79.0%), and median age 41 (range 24-61)
      years. Vector exposure was high with 64% seropositive for Ph. alexandri saliva
      antibodies. Prevalence of AVL (any positive test result) was 39/200 (19.5%, 95%
      CI 14.4%-25.8%). No subjects had positive rK39 test results. Two (1.0%) PCR, ten
      (5%) ELISA, and 28 (14%) IGRA samples were positive. Travel to Ninewa governorate
      increased risk for AVL (p=0.01). Conclusion: AVL was identified in 19.5 % of OIF
      deployers and travel to northwest Iraq correlated with infection. Further studies
      are needed to inform risk for reactivation VL in U.S. veterans and to target
      additional blood safety and surveillance measures.

PMID- 30239633
TI  - Haemodynamic assessment of bicuspid aortic valve aortopathy: a systematic review
      of the current literature.
AB  - Both genetic and haemodynamic theories explain the aetiology, progression and
      optimal management of bicuspid aortic valve aortopathy. In recent years, the
      haemodynamic theory has been explored with the help of magnetic resonance imaging
      and computational fluid dynamics. The objective of this review was to summarize
      the findings of these investigations with focus on the blood flow pattern and
      associated variables, including flow eccentricity, helicity, flow displacement,
      cusp opening angle, systolic flow angle, wall shear stress (WSS) and oscillatory
      shear index. A structured literature review was performed from January 1990 to
      January 2018 and revealed the following 3 main findings: (i) the bicuspid aortic
      valve is associated with flow eccentricity and helicity in the ascending aorta
      compared to healthy and diseased tricuspid aortic valve, (ii) flow displacement
      is easier to obtain than WSS and has been shown to correlate with valve
      morphology and type of aortopathy and (iii) the stenotic bicuspid aortic valve is
      associated with elevated WSS along the greater curvature of the ascending aorta,
      where aortic dilatation and aortic wall thinning are commonly found. We conclude
      that new haemodynamic variables should complement ascending aorta diameter as an
      indicator for disease progression and the type and timing of intervention. WSS
      describes the force that blood flow exerts on the vessel wall as a function of
      viscosity and geometry of the vessel, making it a potentially more reliable
      marker of disease progression.

PMID- 30239636
TI  - Seasonal Influenza Vaccine Impact on Pandemic H1N1 Vaccine Efficacy.
AB  - Background: In 2009, a novel influenza A (pH1N1) was identified, resulting in a
      pandemic with significant morbidity and mortality. A monovalent pH1N1 vaccine was
      separately produced in addition to the seasonal trivalent influenza vaccine.
      Formulation of the seasonal influenza vaccine (injectable trivalent inactivated
      influenza vaccine [TIV] vs. intranasal live, attenuated influenza vaccine [LAIV])
      was postulated to have impacted the efficacy of the pH1N1 vaccination. Methods:
      We reviewed electronic health and manpower databases, which included vaccination
      records, along with healthcare encounters for influenza-like illness (ILI),
      influenza, and pneumonia among US military members (aged 18-49 years) in the
      contiguous United States. We examined rates by vaccination type to identify
      potential factors associated with the risk for study outcomes. Results: Compared
      with those receiving the seasonal influenza vaccine alone, subjects receiving the
      pH1N1 vaccine, either alone (RR, 0.49) or in addition to the seasonal vaccine
      (RR, 0.51), had an approximately 50% reduction in ILI, 88% reduction in influenza
      (RR, 0.11 and 0.12, respectively), and 63% reduction in pneumonia (RR, 0.37 and
      0.35, respectively). There was no clinically significant difference in ILI,
      influenza, or pneumonia attack rates among those receiving the pH1N1 vaccine with
      or without presence of the seasonal vaccine. Similarly, there was no clinically
      relevant difference in pH1N1 effectiveness between seasonal TIV and LAIV
      recipients. Conclusions: During the 2009-2010 pandemic, the pH1N1 vaccination was
      effective in reducing rates of ILI, influenza, and pneumonia in young healthy
      adults. Administration of the seasonal vaccine should continue without concern of
      potential interference with a novel pandemic vaccine, though more studies are
      needed to determine if this is applicable to other influenza seasons.

PMID- 30239635
TI  - Focus on echovascular imaging assessment of arterial disease: complement to the
      ESC guidelines (PARTIM 1) in collaboration with the Working Group on Aorta and
      Peripheral Vascular Diseases.
AB  - The main goal of the present document is to provide a set of practical
      recommendations for ultrasound imagers who are interested in artery diseases or
      for physicians who intend to undertake vascular procedures. This is the first
      part of the work. It is dedicated to general principles of ultrasonography,
      cervicoencephalic, subclavian, aortoiliac and lower extremity arteries, abdominal
      aorta, and popliteal aneurysms. It also discusses miscellaneous items such as
      medial arterial calcinosis, arterial embolism, arteritis, arterial stents and
      bypasses, false aneurysms, aortic dissection, popliteal entrapment syndrome, and
      iliac endofibrosis.

PMID- 30239637
TI  - Decline in Pneumococcal Disease Attenuated in Older Adults and Those with
      Comorbidities Following Universal Childhood PCV13 Immunization.
AB  - Introduction: Following introduction of PCV7 in the US, epidemiology of
      pneumococcal disease shifted such that disease incidence in the elderly exceeded
      that in children. We evaluated the impact of replacing PCV7 with PCV13 on disease
      burden in adults, and identified age/risk-specific subgroups with highest
      remaining disease burden. Methods: A retrospective design and data from two US
      healthcare claims repositories were employed. Study population included adults
      aged >=18 years, and was stratified by age (18-49, 50-64, 65-74, >=75) and risk
      profile (healthy, at-risk, high-risk). Rate ratios comparing invasive
      pneumococcal disease (IPD), all-cause hospitalized pneumonia (ACHP), and
      pneumococcal pneumonia requiring hospitalization among at-risk and high-risk
      adults, versus healthy counterparts, were estimated for 2007-2010 (pre-PCV13),
      2011-2012 (peri-PCV13), and 2013-2015 (post-PCV13). Results: Across study
      periods, IPD and ACHP rates increased with age (2-27x higher in persons >=75 vs.
      18-49) and comorbidity (4-20x higher in high-risk vs. healthy). From pre- to post
      PCV13 period, IPD rates declined 5-48% and ACHP rates declined 4-19% across age
      and risk groups (ACHP did not decline in persons >=75). The decline in IPD and
      ACHP was attenuated among older adults and those with comorbidities; accordingly,
      rate ratios among at-risk and high-risk persons (vs. healthy counterparts)
      increased during the peri- and post-PCV13 periods compared with the pre-PCV13
      period. Conclusions: The switch to PCV13 was associated with large declines in
      pneumococcal disease among US adults. However, the decline was attenuated with
      increasing age (and, for ACHP, was absent in persons >=75) and in those with
      comorbidities.

PMID- 30239634
TI  - Reducing Glucokinase Activity Restores Endogenous Pulsatility and Enhances
      Insulin Secretion in Islets From db/db Mice.
AB  - An early sign of islet failure in type 2 diabetes (T2D) is the loss of normal
      patterns of pulsatile insulin release. Disruptions in pulsatility are associated
      with a left shift in glucose sensing that can cause excessive insulin release in
      low glucose (relative hyperinsulinemia, a hallmark of early T2D) and beta-cell
      exhaustion, leading to inadequate insulin release during hyperglycemia. Our
      hypothesis was that reducing excessive glucokinase activity in diabetic islets
      would improve their function. Isolated mouse islets were exposed to glucose and
      varying concentrations of the glucokinase inhibitor d-mannoheptulose (MH) to
      examine changes in intracellular calcium ([Ca2+]i) and insulin secretion. Acutely
      exposing islets from control CD-1 mice to MH in high glucose (20 mM) dose
      dependently reduced the size of [Ca2+]i oscillations detected by fura-2
      acetoxymethyl. Glucokinase activation in low glucose (3 mM) had the opposite
      effect. We then treated islets from male and female db/db mice (age, 4 to 8
      weeks) and heterozygous controls overnight with 0 to 10 mM MH to determine that 1
      mM MH produced optimal oscillations. We then used 1 mM MH overnight to measure
      [Ca2+]i and insulin simultaneously in db/db islets. MH restored oscillations and
      increased insulin secretion. Insulin secretion rates correlated with MH-induced
      increases in amplitude of [Ca2+]i oscillations (R2 = 0.57, P < 0.01, n = 10) but
      not with mean [Ca2+]i levels in islets (R2 = 0.05, not significant). Our findings
      show that correcting glucose sensing can restore proper pulsatility to diabetic
      islets and improved pulsatility correlates with enhanced insulin secretion.

PMID- 30239638
TI  - Poor performance of rapid molecular tests to define eligibility for the
      shortcourse MDR-TB regimen.
AB  - The World Health Organization recommends short course regimen (SCR) to treat
      multidrug resistant tuberculosis for patients with strains susceptible by line
      probe assays (LPAs) to second-line drugs. Our retrospective study shows LPAs have
      suboptimal specificity in predicting eligibility for SCR; a quarter of eligible
      patients would receive inadequate therapy with SCR.

PMID- 30239639
TI  - Pulmonary diffusion capacity predicts major complications after esophagectomy for
      patients with esophageal cancer.
AB  - A reduced forced expiratory volume in one second (FEV1) is a well-recognized risk
      factor for complications after esophagectomy. Lung diffusing capacity for carbon
      monoxide (DLCO) is not routinely integrated in the risk assessment of
      esophagectomy. The aim of this study is to evaluate the association of
      preoperative pulmonary function tests with major postoperative complications
      after esophagectomy for cancer. In order to achieve this aim, 459 patients with
      newly diagnosed esophageal cancer who underwent elective transthoracic (n = 352)
      or transhiatal (n = 107) surgical resection of the esophagus with cervical
      anastomosis between 2003 and 2015 were analyzed. Multivariable logistic
      regression analysis was performed to assess the association of preoperative
      pulmonary function tests (expressed as % of predicted) with major complications
      after esophagectomy, adjusted for previously identified predictors. Major
      complications were defined as Clavien-Dindo grade IIIb or higher. Of the 459
      included patients, 114 (24.8%) developed major complications. In univariable
      analysis FEV1, forced vital capacity (FVC), vital capacity (VC), and DLCO were
      associated with major complications. After adjusting each pulmonary function test
      for age, American Society of Anesthesiologists (ASA) score, cardiac comorbidity,
      diabetes mellitus, peripheral vascular disease, and surgical approach, FVC (OR:
      1.24 per 10% decrease; 95% CI: 1.06-1.45; P = 0.004), VC (OR: 1.19 per 10%
      decrease; 95% CI: 1.02-1.39; P = 0.025) and DLCO (OR: 1.16 per 10% decrease;
      95%CI: 1.02-1.33; P = 0.025) remained predictive factors for major surgical
      complications. In multivariable analysis in which all pulmonary functions tests
      were combined, DLCO was the strongest predictor of major complications (OR: 1.14
      per 10% increase; 95% CI: 1.01-1.30; P = 0.046). The ideal cut-off for DLCO% of
      predicted was determined at <84% (OR: 1.97; 95% CI: 1.28-3.03; P = 0.002). These
      data indicate that DLCO is an independent predictor of major complications after
      esophagectomy for cancer. This pulmonary function test deserves greater
      consideration in prediction research of major complications after esophagectomy.

PMID- 30239640
TI  - Do dysplastic proximal resection margins predict the risk of anastomotic
      recurrence and overall survival in patients with esophageal squamous cell
      carcinoma?
AB  - Positive proximal resection margins are strongly associated with anastomotic
      recurrence in esophageal cancer. However, the prognostic significance of
      dysplastic proximal resection margins remains unclear. The aim of this study is
      to investigate whether the dysplastic proximal resection margin can predict
      anastomotic recurrence and overall survival in patients with esophageal squamous
      cell carcinoma. Between 2000 and 2014, patients with esophageal squamous cell
      carcinoma who received a nonpalliative resection and survived the perioperative
      period were included. Two expert pathologists independently reviewed the proximal
      resection margin status, which was classified as negative, dysplastic, or
      positive. The kappa statistic was used to test interobserver reliability.
      Anastomotic recurrence and overall survival served as the main outcome measures.
      The study cohort consisted of 469 patients (445 males and 27 females). There was
      an excellent interobserver agreement for negative (kappa = 0.88), dysplastic
      (kappa = 0.88), and positive (kappa = 1) proximal resection margins-which were
      identified in 418 (89.1%), 37 (7.9%), and 14 (3.0%) patients, respectively. After
      a median follow-up of 21.6 months, 30 (6.4%) patients developed an anastomotic
      recurrence. Compared with patients with negative proximal resection margins
      (24/418, 5.7%), the occurrence of anastomotic recurrence was more commonly
      observed in those with positive proximal resection margins (3/14, 21.4%, P =
      0.017) but not in those with dysplastic proximal resection margins (3/37, 8.1%, P
      = 0.56). Multivariable Cox regression analysis identified positive proximal
      resection margins (hazard ratio: 5.93, P = 0.010) and advanced clinical stage
      (hazard ratio: 12.04, P = 0.023) as independent risk factors for anastomotic
      recurrence. Dysplastic proximal resection margins were not retained in the model
      as an independent predictor (hazard ratio: 1.38, P = 0.602). The 5-year overall
      survival rates of patients with negative (38.2%) and dysplastic margins (27.0%)
      were similar (P = 0.814), and significantly higher than that observed in those
      with positive proximal resection margins (9.5%, P = 0.015). In conclusion,
      dysplastic proximal resection margins can be identified in at least 7.9% of
      patients with esophageal squamous cell carcinoma, but neither they are associated
      with an increased risk of anastomotic recurrence nor they portend a poor overall
      survival.

PMID- 30239643
TI  - Retrieval team-initiated early donor management increases the donor heart
      utilization rate for transplantation.
AB  - OBJECTIVES: Heart transplantation represents the most effective therapy that is
      currently available for end-stage heart failure. Despite the shortage of organ
      donors, many donor hearts are not accepted for transplantation due to poor
      function. Targeted donor management may increase the donor heart utilization
      rate. The aim of this study is to analyse a 2-year experience of early donor
      management through the 'scout programme' by a high-volume national cardiothoracic
      organ retrieval team. METHODS: A prospective cohort study was carried out between
      2013 and 2015 on consecutive donation from brain-dead donors. A member of the
      cardiothoracic retrieval team travelled to the intensive care unit of the donor
      hospital to assist with early management. RESULTS: One hundred and seventy-eight
      cardiac donors were enrolled; 106 (59.5%) were 'scouted', and 72 (40.5%) were
      'non-scouted'. Donor heart utilization rate in the 'scouted' group was 47.2%
      (50/106) compared with 30.6% (22/72) in the 'non-scouted' group (P = 0.03). On
      logistic regression analysis, early donor management by the scouts independently
      predicted donor heart utilization. The time in the operating theatre from donor
      arrival to skin incision was significantly reduced in the 'scouted' group. No
      differences were found in the 30-day graft failure rate or the 30-day, 1-year and
      2-year mortality rates of the recipients between the 2 groups. CONCLUSIONS: Early
      donor management delivered by the cardiothoracic retrieval team significantly
      increased the donor heart utilization rate from existing donors. Moreover, the
      time in the operating theatre from donor heart arrival to skin incision was
      significantly reduced.

PMID- 30239644
TI  - Higher Infliximab Trough Levels Are Associated With Better Outcome in Paediatric
      Patients With Inflammatory Bowel Disease.
AB  - Background: The role of therapeutic drug monitoring for infliximab [IFX] therapy
      in children with inflammatory bowel disease [IBD] is poorly investigated. We
      determined if IFX exposure correlates with long-term remission in children.
      Methods: In this retrospective study, all children with Crohn's disease [CD] and
      ulcerative colitis [UC], receiving maintenance IFX at our centre, were included.
      Serum trough levels and cumulative drug exposure were correlated with clinical,
      biological, and endoscopic remission. All children received proactive drug
      monitoring and dose adaptation aiming to target a therapeutic window of 3-7
      ug/mL. All data are presented as median [interquartile range]. Results: A total
      of 686 serum levels during IFX maintenance in 52 paediatric patients [33 CD and
      19 UC] were included (median 9 [4-18] per patient). With a median of 17 [8-36]
      months under IFX therapy, 39/52 [75%] patients were in clinical remission and
      29/40 [73%] patients were in endoscopic remission. Median IFX trough levels were
      significantly higher when children achieved clinical remission (5.4 [3.8-8.0]
      ug/mL versus 4.2 [2.6-6.7] ug/mL), biological remission (5.2 [3.7-7.7] ug/mL
      versus 4.2 [2.6-6.5] ug/mL), combined clinical and biological remission (5.7 [4.0
      8.2] ug/mL versus 4.4 [2.7-6.8] ug/mL) and endoscopic remission (6.5 [4.2-9.5]
      ug/mL versus 3.2 [2.3-5.6] ug/mL) compared with not meeting these criteria [all p
      <= 0.001]. Conclusions: In this large paediatric cohort, children with clinical
      and/or endoscopic remission had significantly higher IFX exposure during
      maintenance therapy. We showed excellent outcome data using serial and systematic
      measurements of drug levels. This could provide a rationale for the use of
      proactive drug monitoring in children in order to improve long-term outcomes.

PMID- 30239642
TI  - Models and Tools for Studying Enteroendocrine Cells.
AB  - Gut hormones produced by gastrointestinal enteroendocrine cells modulate key
      physiological processes including glucose homeostasis and food intake, making
      them potential therapeutic candidates to treat obesity and diabetes.
      Understanding the function of enteroendocrine cells and the molecular mechanisms
      driving hormone production is a key step toward mobilizing endogenous hormone
      reserves in the gut as a therapeutic strategy. In this review, we will discuss
      the variety of ex vivo and in vitro model systems driving this research and their
      contributions to our current understanding of nutrient-sensing mechanisms in
      enteroendocrine cells.

PMID- 30239641
TI  - A feedback loop between dipeptide-repeat protein, TDP-43 and karyopherin-alpha
      mediates C9orf72-related neurodegeneration.
AB  - Accumulation and aggregation of TDP-43 is a major pathological hallmark of
      amyotrophic lateral sclerosis and frontotemporal dementia. TDP-43 inclusions also
      characterize patients with GGGGCC (G4C2) hexanucleotide repeat expansion in
      C9orf72 that causes the most common genetic form of amyotrophic lateral sclerosis
      and frontotemporal dementia (C9ALS/FTD). Functional studies in cell and animal
      models have identified pathogenic mechanisms including repeat-induced RNA
      toxicity and accumulation of G4C2-derived dipeptide-repeat proteins. The role of
      TDP-43 dysfunction in C9ALS/FTD, however, remains elusive. We found G4C2-derived
      dipeptide-repeat protein but not G4C2-RNA accumulation caused TDP-43
      proteinopathy that triggered onset and progression of disease in Drosophila
      models of C9ALS/FTD. Timing and extent of TDP-43 dysfunction was dependent on
      levels and identity of dipeptide-repeat proteins produced, with poly-GR causing
      early and poly-GA/poly-GP causing late onset of disease. Accumulating cytosolic,
      but not insoluble aggregated TDP-43 caused karyopherin-alpha2/4 (KPNA2/4)
      pathology, increased levels of dipeptide-repeat proteins and enhanced G4C2
      related toxicity. Comparable KPNA4 pathology was observed in both sporadic
      frontotemporal dementia and C9ALS/FTD patient brains characterized by its nuclear
      depletion and cytosolic accumulation, irrespective of TDP-43 or dipeptide-repeat
      protein aggregates. These findings identify a vicious feedback cycle for
      dipeptide-repeat protein-mediated TDP-43 and subsequent KPNA pathology, which
      becomes self-sufficient of the initiating trigger and causes C9-related
      neurodegeneration.

PMID- 30239645
TI  - Limited Coverage of Hepatitis C Virus Testing in the United States, 2013-2017.
AB  - In the U.S. household population, HCV testing coverage marginally increased
      between 2013 and 2017 among persons born in 1966-1994 (13.2% to
      16.8%;Ptrend<0.001) and persons born in 1945-1965 (12.3% to 17.3%;Ptrend<0.001).
      In both populations, disparities in testing coverage were noted by education
      level, type of health insurance coverage, and geographic region.

PMID- 30239646
TI  - A crosssectional analysis of Facebook comments to study public perception of a
      new diagnostic test called the Cytosponge.
AB  - Social media provides a useful platform for informal discussions about
      healthcare. Acceptability is key to the uptake of diagnostic devices and this can
      be difficult to gauge from questionnaires and qualitative studies. The aim of
      this study is to investigate whether Facebook could be used to gauge public
      perception toward uptake of a new diagnostic test for Barrett's esophagus called
      the Cytosponge. We retrospectively reviewed Facebook comments relating to a video
      on the Cytosponge. We categorized comments into: (1) Positive, (2) Negative, (3)
      Unknown and (4) Questions. Recurring themes that arose were compared to a
      qualitative study on the Cytosponge. The video received 22.5 million views and
      2837 comments within four months. Of these, 525 comments were positive, 215 were
      unknown, 179 were negative, 71 were questions, and 1847 were 'Tagged' comments.
      Among positive comments, recurrent themes were that it was innovative, could lead
      to early cancer-detection, and more favorable than endoscopy. Among negative
      comments, a recurring theme was concern about the risk of gagging and vomiting.
      Among 'questions', a recurring theme was related to the risk of Cytosponge
      detachment. We compared our analysis to a published qualitative study and found
      similar themes arose across both studies. Facebook provides a rich source of
      qualitative data, which could be used to augment studies to gauge public
      perception toward a new diagnostic test.

PMID- 30239647
TI  - Computed tomography myocardial perfusion imaging vs. computed tomography-derived
      fractional flow reserve, which way forward?

PMID- 30239648
TI  - A (glyco)biomarker that predicts failure to standard therapy in Ulcerative
      Colitis patients.
AB  - Background and Aims: There is a clinical need to identify biomarkers able to
      select patients who are most likely to develop aggressive/complicated disease and
      early select them for appropriate therapy. Changes in the glycosylation profile
      of intestinal lymphocytic infiltrate was previously demonstrated to regulate T
      cell activity being associated with disease severity in ulcerative colitis (UC)
      patients. We interrogated whether this heterogeneous expression of branched N
      glycans on intestinal inflammatory infiltrate predict therapy response early in
      disease course. Methods: The expression levels of the branched N-glycans in
      colonic biopsies collected around time of diagnosis from a well-characterized
      cohort of 131 UC patients were correlated with response to standard therapy. ROC
      analysis and specificity/sensitivity were determined. Results: Branched N-glycans
      levels around time of diagnosis predict non-response to conventional therapy with
      75% of specificity. Moreover, high levels of branched N-glycans predict 78% of UC
      patients that will display a favorable disease course (exclusively under 5-ASA
      therapy with more than 5 years the disease). The best predictive performance was
      observed in severe UC patients with Mayo endoscopic subsore 3 and in those that
      were naive for therapy. Multivariable analysis revealed that low levels of
      branched N-glycans and high levels of C Reactive Protein (CRP) around time of
      diagnosis act as independent predictors of non-response to standard therapy. A
      powerful effect of the combined use of the branched N-glycans and CRP was
      observed. Conclusion: Our results reveal a potential (glyco)biomarker that
      predicts, early in the disease course, patients that will fail to respond to
      standard therapy, benefiting thereby from other therapeutic strategies as
      biologics.

PMID- 30239649
TI  - Sarcopenia, the depletion of muscle mass, an independent predictor of respiratory
      complications after oncological esophagectomy.
AB  - Surgery for esophageal carcinoma is known to be associated with high morbidity.
      Recent studies have reported a correlation of nutritional and inflammatory
      parameters with postoperative course. This study aims to clarify the risk factors
      for operative morbidity after resection of esophageal carcinoma. Consecutive
      patients who underwent esophagectomy for esophageal squamous cell carcinoma at
      our institute were included (n = 102; 89 males and 13 females; mean age: 67.3
      years). Clinicopathological characteristics, presence or absence of sarcopenia,
      and modified Glasgow prognostic score were assessed, and their correlation with
      postoperative complications was investigated using univariate and multivariate
      analyses. Sarcopenia was defined using a combination of muscle mass area and body
      mass index. Of the included 102 patients, 45 (44.1%) exhibited sarcopenia
      (sarcopenia group), while 57 (55.9%) did not (non-sarcopenia group). No
      significant difference was observed between the groups regarding surgical
      procedures and tumor stage; furthermore, there was no mortality. Twenty-six
      patients developed respiratory complications (including 20 cases of pneumonia).
      On univariate analysis, sarcopenia, modified Glasgow prognostic score, and
      American Society of Anesthesiologists physical status were found to be
      significantly associated with the development of postoperative respiratory
      complications. On multivariate analysis, sarcopenia was found to be an
      independent risk factor for postoperative respiratory complications after
      esophagectomy. We believe that identifying patients at risk and providing
      preoperative nutritional support as well as physical therapy aimed at
      strengthening of body muscles may help reduce the incidence of postoperative
      respiratory complications in such patients.

PMID- 30239650
TI  - Improvement in Hepatic Fibrosis Biomarkers Associated with Chemokine Receptor
      Inactivation through Mutation or Therapeutic Blockade.
AB  - Background: CCR5 is a key receptor for HIV-1 viral entry into T-cells and a
      variant allele, CCR5 delta-32, is associated with decreased viral replication and
      disease progression. Active HIV-1 replication is highly associated with
      accelerated rates of hepatic fibrosis. We postulated that CCR5 plays a central
      role in the development of hepatic fibrosis, and evaluated the longitudinal
      effect of both natural or drug-induced CCR5 mutation and blockade on biomarkers
      of liver fibrosis in HIV-1 infected patients. Methods: To accomplish this goal,
      we examined two distinct cohorts. First, we evaluated fibrosis markers in the
      Multicenter Hemophilia Cohort Studies (MCHS) which included subjects with HIV and
      HCV coinfection with the CCR5 delta-32 allele. We also evaluated an HIV-1
      infected cohort that was treated with a dual CCR5/CCR2 antagonist, cenicriviroc.
      The Enhanced Liver Fibrosis (ELF) Index was validated against liver histology
      obtained from HCV/HIV coinfected and HCV monoinfected patients and demonstrated
      strong correlation with fibrosis stage. Results: In both the MHCS patients and
      among patients treated with cenicriviroc, CCR5 mutation or blockade was
      associated with a significant decrease in the validated fibrosis biomarker. Among
      the patients with the delta-32 allele, the ELF Index rate significantly decreased
      in sequential samples as compared to CCR5 wildtype patients (p = 0.043). This was
      not observed in control subjects treated with efavirenz nor with a lower dose of
      100 mg CVC. Conclusion: These finding strongly suggest that hepatic fibrosis in
      HIV-1 infected patients can be modulated by the mutation of CCR5 and/or use of
      CCR5/CCR2 blockade agents.

PMID- 30239651
TI  - WebIBD: How Much Can We Trust Medical Information Online?

PMID- 30239652
TI  - Cutavirus DNA in malignant and non-malignant skin of cutaneous T-cell lymphoma
      and organ transplant patients but not of healthy adults.
AB  - Background: Three new parvoviruses of Protoparvovirus genus, bufavirus (BuV),
      tusavirus (TuV) and cutavirus (CuV), have recently been discovered in diarrheal
      stools. CuV was further detected in a proportion of cutaneous T-cell
      lymphoma/mycosis fungoides (CTCL/MF) skin samples and in one melanoma. Patients
      and methods: With novel multiplex quantitative PCR (qPCR) and antibody assays, we
      studied three patient groups for BuV, TuV and CuV DNA and IgG: CTCL patients,
      immunosuppressed solid-organ transplant recipients, and immunocompetent healthy
      adults. Results: CuV DNA was detected in skin biopsies of 4/25 (16.0%) CTCL and
      4/136 (2.9%) transplant patients, but not in any of 159 skin samples of 98
      healthy adults. The dermal CuV-DNA prevalence was significantly higher in CTCL
      patients than in the other subjects. CuV DNA was further detected in healthy skin
      of four organ transplant recipients, two of whom also had CuV-positive skin
      carcinomas. One CTCL patient harbored CuV DNA in both malignant (CTCL, melanoma)
      and non-malignant skin and sentinel lymph nodes, but not in his prostate. The CuV
      IgG seroprevalences were among CTCL patients 9.5% (4/42), transplant recipients
      6.5% (8/124), and healthy adults 3.8% (3/78). BuV and TuV DNAs were absent and
      antibodies infrequent in all cohorts. Parvoviral antibodies were shown to persist
      for >=20 years and dermal CuV DNA for four years. All three CuV-DNA-positive
      patients, with both biopsies and sera available, were CuV-IgG positive.
      Conclusion: Our results suggest that dermal CuV DNA carriage is associated with
      CTCL. Any putative roles of CuV in the carcinogenesis must be determined in
      forthcoming studies.

PMID- 30239653
TI  - Predictors of quality of life in young adults with congenital heart disease.
AB  - Aims: The aim of this study was to identify medical and psychosocial risk factors
      for impaired health-related quality of life (HRQoL) and poor psychological
      adjustment (PA) in young adults with congenital heart disease (CHD). Methods and
      Results: A group of 188 patients (43% females, ages 18-30 years) with various
      types of CHD and 139 age-matched healthy controls (57% females) completed
      questionnaires assessing HRQoL, PA, social support, significant life events in
      the past year, education level, civil status, and employment status. Medical
      variables were retrieved from the patients' hospital records. Patients reported
      worse physical HRQoL than controls but similar mental HRQoL and PA. Female CHD
      patients showed worse physical and mental HRQoL and poorer PA than males. In CHD
      patients, a lower educational level and lower physical exercise capacity
      predicted lower physical HRQoL, but complexity of CHD was not related to HRQoL or
      PA. Less social support was associated with lower mental HRQoL and poorer PA in
      CHD patients. Conclusion: Young adults with CHD have impaired physical HRQoL but
      normal mental HRQoL and PA. Lower physical exercise capacity, female sex, less
      social support and lower educational level predict an unfavorable quality of life
      and PA. This subgroup of patients should be monitored more closely and provided
      with special psychosocial care to improve long-term outcome.

PMID- 30239654
TI  - The Epidemiology and Clinical Features of Balamuthia mandrillaris Disease in the
      United States, 1974 - 2016.
AB  - Background: Balamuthia mandrillaris is a free-living ameba that causes rare,
      nearly always fatal disease in humans and animals worldwide. B. mandrillaris has
      been isolated from soil, dust, and water. Initial entry of Balamuthia into the
      body is likely via the skin or lungs. To date, only individual case reports and
      small case series have been published. Methods: The Centers for Disease Control
      and Prevention (CDC) maintains a free-living ameba (FLA) registry and laboratory.
      To be entered into the registry, a Balamuthia case must be laboratory-confirmed.
      Several sources were used to complete entries in the registry, including case
      report forms, CDC laboratory results, published case reports, and media
      information. SAS(c) version 9.3 software was used to calculate descriptive
      statistics and frequencies. Results: We identified 109 case reports of Balamuthia
      disease between 1974 and 2016. Most (99%) had encephalitis. The median age was 36
      years (range 4 months to 91 years). Males accounted for 68% of the case patients.
      California had the highest number of case reports followed by Texas and Arizona.
      Hispanics constituted 55% for those with documented ethnicity. Exposure to soil
      was commonly reported. Among those with a known outcome, 90% of patients died.
      Conclusions: Balamuthia disease in the United States is characterized by a highly
      fatal encephalitis that affects patients of all ages. Hispanics were
      disproportionately affected. The southwest region of the U.S. reported the most
      cases. Clinician awareness of Balamuthia as a cause of encephalitis might lead to
      earlier diagnosis and initiation of treatment, resulting in better outcomes.

PMID- 30239655
TI  - The human mesenteric lymph node microbiome differentiates between Crohn's disease
      and ulcerative colitis.
AB  - Background and Aims: Mesenteric lymph nodes are sites in which translocated
      bacteria incite and progress immunological responses. For this reason,
      understanding the microbiome of mesenteric lymph nodes in inflammatory bowel
      disease is important. The bacterial profile of Crohn's disease mesenteric lymph
      nodes has been analysed using culture-independent methods in only one previous
      study. This study aimed to investigate the mesenteric lymph node microbiota from
      both Crohn's disease and ulcerative colitis patients. Methods: Mesenteric lymph
      nodes were collected from Crohn's disease and ulcerative colitis patients
      undergoing resection. Total DNA was extracted from mesenteric lymph nodes and
      assessed for the presence of bacterial DNA (16S). All work was completed in a
      sterile environment using aseptic techniques. Samples positive for 16S DNA
      underwent next generation sequencing and the identity of bacterial phyla and
      species were determined. Results: Crohn's disease mesenteric lymph nodes had a
      distinctly different microbial profile to that observed in ulcerative colitis.
      The relative abundance of Firmicutes was greater in nodes from ulcerative colitis
      patients while Proteobacteria were more abundant in Crohn's disease. Although
      species diversity was reduced in Crohn's disease mesenteric lymph nodes, they
      contained greater numbers of less dominant phyla, mainly Fusobacteria.
      Conclusion: This study confirms that there are distinct differences between the
      Crohn's disease and ulcerative colitis mesenteric lymph node microbiomes. Such
      microbial differences could aid in the diagnosis of Crohn's disease or ulcerative
      colitis, particular in cases of indeterminate colitis at time of resection, or
      help explain their mechanisms of development and progression.

PMID- 30239656
TI  - An examination of opioid prescription for Medicare Part D patients among family
      practice prescribers.
AB  - Background: In the USA, opioid overdose accounted for more than 60% of drug
      overdose deaths in 2015. Of these deaths, 40% were due to use of prescription
      opioids. Objectives: The aims of the study were to (i) study family medicine
      physician opioid-prescribing rate and duration of prescription, (ii) study the
      distribution of prescription by medication potency, (iii) study opioid
      prescribing trends in health care shortage areas and (iv) study the association
      between extreme high prescribing rates and medical board discipline. Methods:
      This is a retrospective cross-sectional study of the 2015 Medicare Part D claim
      data. Results: Family practitioners have opioid prescription rates (5.6%) similar
      to medical subspecialists (6.0%), but lower than pain specialists (53.2%) and
      surgical specialists (36.6%). Family practitioners have an average opioid
      prescription duration (21.5 days) similar to medical subspecialists (23.1 days)
      and pain specialists (27.1 days), but longer than surgical specialists (8.9
      days). Family practitioners tend to prescribe lower potency opioids. Family
      practitioners in rural health care shortage areas have a higher opioid
      prescription rate than other family practitioners (6.5% versus 5.6%). Among the
      52 family practitioners who prescribed opioids as frequently as pain specialists,
      26 of the 52 (50%) were certified in pain management or worked with a partner
      certified in pain management. Of the other 26 family practitioners, 3 (12%) had
      medical board disciplinary actions regarding opioid prescription. Conclusions:
      While monitoring extreme prescribers is important and needs to be continued, the
      next step in policies to reduce prescription opioids will require systemic
      change, especially providing support for family practitioners in rural health
      care shortage areas.

PMID- 30239657
TI  - Mucin degradation niche as a driver of microbiome composition and Akkermansia
      muciniphila abundance in a dynamic gut model is donor independent.
AB  - Akkermansia muciniphila, an abundant mucin degrading intestinal bacterium, has
      been correlated with human health in various studies. The in vitro SHIME model
      was used to reach a mechanistic understanding of A. muciniphila's colonization
      preferences and its response to environmental parameters such as colon pH and
      mucins. These insight can help to identify the optimal conditions for successful
      in vivo application. After a period of mucin deprivation, we found that mucin
      supplementation resulted in significantly different microbial communities, with
      more Akkermansia, Bacteroides and Ruminococcus. Mucin treatment accounted for 26%
      of the observed variation in the microbial community at OTU level (P = 0.001),
      whereas the donor effect was limited (8%) (P = 0.035), indicating mucins to
      constitute an important ecological niche shaping the microbiota composition. The
      effect of colonic pH had a less profound impact on the microbiome with both pH
      and donor origin explaining around 10% of the variability in the dataset. Yet,
      higher simulated colonic pH had a positive impact on Akkermansia abundance while
      short chain fatty acid analysis displayed a preference for propionate production
      with higher colonic pH. Our results show that mucins as nutritional resource are
      a more important modulator of the gut microbiome than colon pH as environmental
      factor.

PMID- 30239658
TI  - Developing and validating the Personal Risk of Oncogenic Human Papillomavirus
      infection score in US Women.
AB  - Background: Determining risk scores for genital high-risk human papillomavirus
      (HRHPV) infection in women will support more efficient cervical cancer screening
      strategies. Objective: We developed and validated point scores to predict the
      likelihood of any genital HRHPV infection in women. Methods: We conducted the
      cross-sectional analysis in 2017 and used data from the 2005-14 US National
      Health and Nutrition Examination Survey (7337 women aged 25-59 years; 6300 women
      aged 30-59 years). Predictors were reproductive health practices, risk behaviors
      and demographic variables. The outcome was a positive result for any of the 21
      genital HRHPV genotypes. The 2005-12 cohorts were used as training and testing
      sets to develop scores that best classified women into three risk groups: low
      risk (<20%), average risk (20-30%) and high risk (>30%). The 2013-14 cohort was
      used to validate the final scores. Results: Two-point scores with six self
      reported variables were created to predict any HRHPV risks for the two age
      groups: the Personal Risk of Oncogenic HPV (PRO-HPV25) for women aged 25-59 years
      old and PRO-HPV30 for women aged 30-59 years old. The scores were successfully
      prospectively validated, with good calibration with regards to the predicted and
      observed rates of HRHPV infection. The scores had fair discrimination (c
      statistics: 0.67-0.68). Conclusion: The PRO-HPV risk scores can identify groups
      at low, average and high risk of genital HRHPV infection. This information can be
      used to prioritize women for cervical cancer screening in low-resource settings
      or to personalize screening intervals.

PMID- 30239659
TI  - Lachancea thermotolerans, a Yeast Symbiont of Yellowjackets, Enhances Attraction
      of Three Yellowjacket Species (Hymenoptera: Vespidae) to Fruit Powder.
AB  - Previously, we showed that the symbiotic yeast Lachancea thermotolerans
      (Filippov) (Saccharomycetales: Saccharomycetaceae) is attractive to its Vespula
      (Hymenoptera: Vespidae) yellowjacket hosts when grown on media supplemented with
      grape juice. We hypothesized that "Concerto", a commercial strain of this yeast,
      could be combined with fruit powder to form a shelf-stable bait for trapping
      yellowjackets. Using molecular techniques, we first confirmed that Concerto yeast
      is indeed the species L. thermotolerans. We then tested whether: 1) Concerto
      yeast produces volatiles similar to those produced by L. thermotolerans isolated
      from yellowjackets, 2) Concerto yeast enhances attraction of yellowjackets to
      fruit powder, 3) a Concerto yeast/fruit powder bait interacts synergistically
      with a yellowjacket semiochemical lure, and 4) a synthetic analog blend of
      Concerto-produced volatiles attracts yellowjackets. Using gas chromatography-mass
      spectrometry, we demonstrated that the chemical composition of Concerto-produced
      volatiles closely resembles that produced by a yellowjacket-isolated strain of L.
      thermotolerans. In field experiments, addition of Concerto to fruit powder
      doubled its attractiveness to yellowjackets. Addition of the Concerto/fruit
      powder bait to a heptyl butyrate-based wasp lure revealed a weak additive effect.
      A three-component synthetic analog blend of volatiles identified from the
      Concerto/fruit powder bait attracted Vespula pensylvanica (Saussure), but no
      other yellowjacket species. Our results suggest that commercial L. thermotolerans
      in combination with fruit powder could be used as a yellowjacket bait, and that
      addition of yeast-produced volatiles to a commercial wasp lure may improve its
      attractiveness to V. pensylvanica. Further research should determine why the
      synthetic volatile blend failed to attract Vespula species other than V.
      pensylvanica.

PMID- 30239660
TI  - Acute prosthetic mitral valve dysfunction due to non-traumatic fracture of
      prosthesis.

PMID- 30239661
TI  - Short-term impacts of anthropogenic stressors on Aedes albopictus mosquito vector
      microbiota.
AB  - Recent studies have highlighted the potential role of microbiota in the biology
      of the Aedes albopictus mosquito vector. This species is highly anthropogenic and
      exhibits marked ecological plasticity, with a resulting high potential to
      colonize a wide range of habitats-including anthropized areas-under various
      climatic conditions. We put forward the hypothesis that climate and anthropogenic
      activities, such as the use of antibiotics in agriculture and human medicine,
      might affect the mosquito-associated bacterial community. We thus studied the
      additive impact of a temperature decrease and antibiotic ingestion on the
      temporal dynamics of Ae. albopictus survival and its associated bacterial
      communities. The results showed no effects of disturbances on mosquito survival.
      However, short-term temperature impacts on bacterial diversity were observed,
      while both the community structure and bacterial diversity were affected by early
      antibiotic ingestion. The genera Elizabethkingia, Chryseobacterium and Wolbachia,
      as well as an unclassified member of the Bacteroidales order were particularly
      affected. Antibiotics negatively impacted Elizabethkingia abundance, while
      Chryseobacterium was completely eliminated following both disturbances, to the
      benefit of Wolbachia and the unclassified Bacteroidales species. These results
      generated fresh insight into the effects of climate and anthropogenic activities
      such as the use of antibiotics on mosquito microbiota.

PMID- 30239662
TI  - Death from stroke in Europe: if you can't measure it, you can't improve it.

PMID- 30239663
TI  - Cardiovascular implantable electronic device infection: time to discuss
      reimbursement-Authors' reply.

PMID- 30239664
TI  - Growing and cultivating the forest genomics database, TreeGenes.
AB  - Forest trees are valued sources of pulp, timber and biofuels, and serve a role in
      carbon sequestration, biodiversity maintenance and watershed stability. Examining
      the relationships among genetic, phenotypic and environmental factors for these
      species provides insight on the areas of concern for breeders and researchers
      alike. The TreeGenes database is a web-based repository that is home to 1790 tree
      species and over 1500 registered users. The database provides a curated archive
      for high-throughput genomics, including reference genomes, transcriptomes,
      genetic maps and variant data. These resources are paired with extensive
      phenotypic information and environmental layers. TreeGenes recently migrated to
      Tripal, an integrated and open-source database schema and content management
      system. This migration enabled developments focused on data exchange, data
      transfer and improved analytical capacity, as well as providing TreeGenes the
      opportunity to communicate with the following partner databases: Hardwood
      Genomics Web, Genome Database for Rosaceae, and the Citrus Genome Database.
      Recent development in TreeGenes has focused on coordinating information for
      georeferenced accessions, including metadata acquisition and ontological
      frameworks, to improve integration across studies combining genetic, phenotypic
      and environmental data. This focus was paired with the development of tools to
      enable comparative genomics and data visualization. By combining advanced data
      importers, relevant metadata standards and integrated analytical frameworks,
      TreeGenes provides a platform for researchers to store, submit and analyze forest
      tree data.

PMID- 30239666
TI  - Wide-scope biomedical named entity recognition and normalization with CRFs, fuzzy
      matching and character level modeling.
AB  - We present a system for automatically identifying a multitude of biomedical
      entities from the literature. This work is based on our previous efforts in the
      BioCreative VI: Interactive Bio-ID Assignment shared task in which our system
      demonstrated state-of-the-art performance with the highest achieved results in
      named entity recognition. In this paper we describe the original conditional
      random field-based system used in the shared task as well as experiments
      conducted since, including better hyperparameter tuning and character level
      modeling, which led to further performance improvements. For normalizing the
      mentions into unique identifiers we use fuzzy character n-gram matching. The
      normalization approach has also been improved with a better abbreviation
      resolution method and stricter guideline compliance resulting in vastly improved
      results for various entity types. All tools and models used for both named entity
      recognition and normalization are publicly available under open license.Database
      URL: https://github.com/TurkuNLP/BioCreativeVI_BioID_assignment.

PMID- 30239667
TI  - Impact of improved urban environment and coaching on physical condition and
      quality of life in elderly women: a controlled study.
AB  - Background: Physical activity can slow the ageing process and preserve autonomy
      in the elderly. The aim of this study was to assess the combined impact of an
      organized urban walking circuit and individual coaching on women senior citizens'
      physical well-being and quality of life. Methods: Insufficiently physically
      active women >65 years were included in a quasi-experimental trial. Active arm:
      District with improved urban environment (IUE). Control arm: District without
      improved urban environment (WIUE). In each district, subjects were randomly
      allocated to receive coaching (C+ vs. C-). The main outcome measures were
      endurance, physical activity score, flexibility, quality of life, physical self
      esteem, ageing exercise stereotypes, functional health and perceived health at
      baseline, three (M3) and six (M6) months. Results: Fifty-two insufficiently
      physically active women were included, 23 in IUE and 29 in WIUE. Groups were
      comparable at baseline. At M3, endurance and physical activity score
      significantly improved compared with baseline in the IUE group and in the C+
      group while no statistically significant change was observed for the WIUE group
      and the C- group. Moreover, endurance score was higher in the IUE group, whether
      coupled with coaching or not. After the coaching was removed, the IUE group
      regresses to baseline overall and the WIUE shows a decrement in endurance.
      Conclusion: Our study highlights the positive impact of an improved environment
      and of individual coaching on the level of physical activity and quality of life
      of insufficiently physically active elderly women.

PMID- 30239665
TI  - Improved ontology for eukaryotic single-exon coding sequences in biological
      databases.
AB  - Efficient extraction of knowledge from biological data requires the development
      of structured vocabularies to unambiguously define biological terms. This paper
      proposes descriptions and definitions to disambiguate the term 'single-exon
      gene'. Eukaryotic Single-Exon Genes (SEGs) have been defined as genes that do not
      have introns in their protein coding sequences. They have been studied not only
      to determine their origin and evolution but also because their expression has
      been linked to several types of human cancer and neurological/developmental
      disorders and many exhibit tissue-specific transcription. Unfortunately, the term
      'SEGs' is rife with ambiguity, leading to biological misinterpretations. In the
      classic definition, no distinction is made between SEGs that harbor introns in
      their untranslated regions (UTRs) versus those without. This distinction is
      important to make because the presence of introns in UTRs affects transcriptional
      regulation and post-transcriptional processing of the mRNA. In addition, recent
      whole-transcriptome shotgun sequencing has led to the discovery of many examples
      of single-exon mRNAs that arise from alternative splicing of multi-exon genes,
      these single-exon isoforms are being confused with SEGs despite their clearly
      different origin. The increasing expansion of RNA-seq datasets makes it
      imperative to distinguish the different SEG types before annotation errors become
      indelibly propagated in biological databases. This paper develops a structured
      vocabulary for their disambiguation, allowing a major reassessment of their
      evolutionary trajectories, regulation, RNA processing and transport, and provides
      the opportunity to improve the detection of gene associations with disorders
      including cancers, neurological and developmental diseases.

PMID- 30239668
TI  - Foraging Phenology of the Fungus-Growing Termite Odontotermes formosanus
      (Blattodea: Termitidae).
AB  - Fungus-growing termites are major contributors to litter decomposition and an
      agriculture pest in tropical and subtropical Africa and Asia. The foraging
      behavior of fungus-growing termites was hypothesized to be seasonal and may
      associate with climatic factors and the occurrence of natural enemies. In this
      study, we tested the effects of climatic factors and the presence of ants on the
      foraging activity of the fungus-growing termite Odontotermes formosanus (Shiraki)
      (Blattodea: Termitidae). Termite-foraging activities were quantified monthly
      based on the number of wood stakes occupied, amount of wood consumed, and
      foraging population size. The rate of wood-stake decomposition was measured by
      monitoring 484 wood stakes in a tropical forest over the course of nearly 6 yr.
      The results revealed that temperature and rainfall are the major climatic factors
      influencing the foraging seasonality of O. formosanus. Termites occupied fewer
      wood stakes during hot-wet seasons when fewer ants were present. The results of a
      path analysis supported that termite-foraging seasonality correlated mainly with
      climatic factors rather than the presence of ants. A new foraging hypothesis, the
      eat-and-run strategy, is proposed to explain the inconsistent seasonal foraging
      behaviors observed in fungus-growing termites.

PMID- 30239669
TI  - Antibiotic resistance genes show enhanced mobilization through suspended growth
      and biofilm-based wastewater treatment processes.

PMID- 30239672
TI  - A new diagnostic test for arrhythmogenic right ventricular cardiomyopathy: is
      this too good to be true?

PMID- 30239671
TI  - Relations between implementation of new treatments and improved outcomes in
      patients with non-ST-elevation myocardial infarction during the last 20 years:
      experiences from SWEDEHEART registry 1995 to 2014.
AB  - Aims: We assessed the changes in short- and long-term outcomes and their relation
      to implementation of new evidence-based treatments in all patients with non-ST
      elevation myocardial infarction (NSTEMI) in Sweden over 20 years. Methods and
      results: Cases with NSTEMI (n = 205 693) between 1995 and 2014 were included from
      the nationwide Swedish Web-System for Enhancement and Development of Evidence
      Based Care in Heart Disease Evaluated According to Recommended Therapies
      (SWEDEHEART) registry. During 20 years in-hospital invasive procedures increased
      from 1.9% to 73.2%, percutaneous coronary intervention or coronary artery bypass
      grafting 6.5% to 58.1%, dual antiplatelet medication 0% to 72.7%, statins 13.3%
      to 85.6%, and angiotensin-converting enzyme inhibitors/angiotensin II receptor
      blocker 36.8% to 75.5%. The standardized 1-year mortality ratio compared with a
      control population decreased from 5.53 [95% confidence interval (CI) 5.30-5.75]
      to 3.03 (95% CI 2.89-3.19). If patients admitted the first 2 years were modelled
      to receive the same invasive treatments as the last 2 years the expected
      mortality/myocardial infarction (MI) rate would be reduced from 33.0% to 25.0%.
      After adjusting for differences in baseline characteristics, the change of 1-year
      cardiovascular death/MI corresponded to a linearly decreasing odds ratio trend of
      0.930 (95% CI 0.926-0.935) per 2-year period. This trend was substantially
      attenuated [0.970 (95% CI 0.964-0.975)] after adjusting for changes in coronary
      interventions, and almost eliminated [0.988 (95% CI 0.982-0.994)] after also
      adjusting for changes in discharge medications. Conclusion: In NSTEMI patients
      during the last 20 years, there has been a substantial improvement in long-term
      survival and reduction in the risk of new cardiovascular events. These
      improvements seem mainly explained by the gradual uptake and widespread use of in
      hospital coronary interventions and evidence-based long-term medications.

PMID- 30239670
TI  - An autoantibody identifies arrhythmogenic right ventricular cardiomyopathy and
      participates in its pathogenesis.
AB  - Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by
      right ventricular myocardial replacement and life-threatening ventricular
      arrhythmias. Desmosomal gene mutations are sometimes identified, but clinical and
      genetic diagnosis remains challenging. Desmosomal skin disorders can be caused by
      desmosomal gene mutations or autoantibodies. We sought to determine if anti
      desmosome antibodies are present in subjects with ARVC. Methods and results: We
      evaluated ARVC subjects and controls for antibodies to cardiac desmosomal
      cadherin proteins. Desmoglein-2 (DSG2), desmocollin-2, and N-cadherin proteins on
      western blots were exposed to sera, in primary and validation cohorts of subjects
      and controls, as well as the naturally occurring Boxer dog model of ARVC. We
      identified anti-DSG2 antibodies in 12/12 and 25/25 definite ARVC cohorts and 7/8
      borderline subjects. Antibody was absent in 11/12, faint in 1/12, and absent in
      20/20 of two control cohorts. Anti-DSG2 antibodies were present in 10/10 Boxer
      dogs with ARVC, and absent in 18/18 without. In humans, the level of anti-DSG2
      antibodies correlated with the burden of premature ventricular contractions (r =
      0.70), and antibodies caused gap junction dysfunction, a common feature of ARVC,
      in vitro. Anti-DSG2 antibodies were present in ARVC subjects regardless of
      whether an underlying mutation was identified, or which mutation was present. A
      disease-specific DSG2 epitope was identified. Conclusion: Anti-DSG2 antibodies
      are a sensitive and specific biomarker for ARVC. The development of autoimmunity
      as a result of target-related mutations is unique. Anti-DSG2 antibodies likely
      explain the cardiac inflammation that is frequently identified in ARVC and may
      represent a new therapeutic target.

PMID- 30239674
TI  - Cardiovascular implantable electronic device infection: time to discuss
      reimbursement.

PMID- 30239673
TI  - Community pharmacies offer a potential high-yield and convenient arena for total
      cholesterol and CVD risk screening.
AB  - Background: Moderately elevated blood total cholesterol (TC), blood glucose (BG)
      and blood pressure (BP) are rarely symptomatic and as such many individuals
      remain untreated. We studied the yield of an in-pharmacy screening for
      identifying undetected high TC and strategies to reach those with absence of
      prior measurement of TC, BG and BP. Methods: A cross-sectional TC screening study
      with complementary TC measurements and self-administered questionnaire was
      conducted for 1 week in each of 2012 and 2014 in 148 and 149 BootsTM Norge AS
      community pharmacies nationwide in Norway. Results: Non-medicated adults (n = 21
      090) with mean age 54.5 +/- 16.0 were included. The study population resembled
      the Norwegian population in regards to body mass index, educational level,
      smokers and physical inactivity level, but with an overrepresentation of middle
      aged women. Of 20 743 with available data, 11% (n = 2337) were unaware of their
      high TC >=7.0 mmol/L, and an additional 8% were unaware of TC >=6.2 mmol/L. More
      than 40% of the study sample had not measured TC or BG before. In order for
      future screenings to reach those who are less likely to have previously measured
      TC and BG, our results suggest that young, low-educated, overweight men and women
      should be targeted for TC measurement, whereas normal weigh men in all ages
      should be targeted for BG measurement. Conclusions: In total 19% in an in
      pharmacy screening were unaware of their elevated TC of >=6.2 mmol/L. We also
      identified characteristics that could be used reach those who are less likely to
      have measured TC and BG.

PMID- 30239675
TI  - Family Practice Launches Partnership with the Committee on Advancing the Science
      of Family Medicine (CASFM).

PMID- 30239676
TI  - Cost-effectiveness of strategies to improve delivery of brief interventions for
      heavy drinking in primary care: results from the ODHIN trial.
AB  - Background: Screening and brief interventions (SBIs) for heavy drinking are an
      effective and cost-effective approach to reducing alcohol-related harm, yet
      delivery rates remain low. This study uses trial data to estimate the cost
      effectiveness of alternative strategies to increase SBI delivery. Methods: Data
      from a large cluster-randomized trial were combined with the Sheffield Alcohol
      Policy Model, a policy appraisal tool, to estimate the cost-effectiveness of
      eight strategies to increase SBI delivery in primary care in England, Poland and
      the Netherlands: care as usual (control), training and support (TS), financial
      reimbursement (FR), referral of patients to an online brief intervention (eBI)
      and all combinations of TS, FR and eBI. cost-effectiveness was assessed from a
      healthcare perspective by comparing health benefits (measured in Quality-Adjusted
      Life Years) with total implementation costs and downstream healthcare savings for
      each strategy over a 30-year horizon and calculating Incremental cost
      effectiveness ratios (ICERs). Results: All trialled strategies were cost
      effective compared to control. TS combined with FR was the most cost-effective
      approach in England (more effective and less costly than control) and Poland
      (ICER ?4632 vs. next-best strategy). This combination is not cost-effective in
      the Netherlands, where TS alone is the most cost-effective approach (ICER ?3386
      vs. next-best strategy). Conclusions: Structured TS, financial incentives and
      access to online interventions are all estimated to be cost-effective methods of
      improving delivery of alcohol brief interventions. TS and FR together may be the
      most cost-effective approach, however this is sensitive to country
      characteristics and alternative BI effect assumptions. Trial registration:
      ClinicalTrials.gov trial identifier: NCT01501552.

PMID- 30239677
TI  - Assisting document triage for human kinome curation via machine learning.
AB  - In the era of data explosion, the increasing frequency of published articles
      presents unorthodox challenges to fulfill specific curation requirements for bio
      literature databases. Recognizing these demands, we designed a document triage
      system with automatic methods that can improve efficiency to retrieve the most
      relevant articles in curation workflows and reduce workloads for biocurators.
      Since the BioCreative VI (2017), we have implemented texting mining processing in
      our system in hopes of providing higher effectiveness for curating articles
      related to human kinase proteins. We tested several machine learning methods
      together with state-of-the-art concept extraction tools. For features, we
      extracted rich co-occurrence and linguistic information to model the curation
      process of human kinome articles by the neXtProt database. As shown in the
      official evaluation on the human kinome curation task in BioCreative VI, our
      system can effectively retrieve 5.2 and 6.5 kinase articles with the relevant
      disease (DIS) and biological process (BP) information, respectively, among the
      top 100 returned results. Comparing to neXtA5, our system demonstrates
      significant improvements in prioritizing kinome-related articles as follows: our
      system achieves 0.458 and 0.109 for the DIS axis whereas the neXtA5's best
      reported mean average precision (MAP) and maximum precision observed are 0.41 and
      0.04. Our system also outperforms the neXtA5 in retrieving BP axis with 0.195 for
      MAP and the neXtA5's reported value was 0.11. These results suggest that our
      system may be able to assist neXtProt biocurators in practice.

PMID- 30239678
TI  - THE-DB: a threading model database for comparative protein structure analysis of
      the E. coli K12 and human proteomes.
AB  - New methodology must be developed to improve the ability to characterize the
      growing number of amino acid sequences, which vastly exceeds the number of
      experimentally determined protein structures. Homologous proteins can be used as
      structural templates for modeling proteins that do not have experimentally
      determined structures. However, in many cases, there are no homologous proteins
      (typically <30% sequence identity) with determined structures from which a query
      sequence can be reliably modeled. The aim of protein threading is to use
      features, such as secondary structure, solvent accessibility and torsional
      angles, in addition to sequence patterns to identify structural templates from
      the protein databank to assist for full-length atomic-level structural modeling.
      However, there are still numerous protein sequences for which correct templates
      cannot be recognized. This raises the question as to what attributes allow query
      sequences to be matched to the correct but distantly homologous templates. To aid
      the investigation into this question and to provide genome-score protein
      structure for the biological community, a database called THE-DB (threading hard
      and easy protein database) has been developed in which it becomes possible to
      analyze over 15 000 query sequences from the Escherichia coli (E. coli) K12 and
      human proteomes, as well as to find their three-dimensional templates derived
      from the state-of-the-art threading algorithms which is not feasible with
      existing protein template databases. The E. coli K12 and human data can be
      downloaded in bulk from the THE-DB page.

PMID- 30239680
TI  - An end-to-end deep learning architecture for extracting protein-protein
      interactions affected by genetic mutations.
AB  - The BioCreative VI Track IV (mining protein interactions and mutations for
      precision medicine) challenge was organized in 2017 with the goal of applying
      biomedical text mining methods to support advancements in precision medicine
      approaches. As part of the challenge, a new dataset was introduced for the
      purpose of building a supervised relation extraction model capable of taking a
      test article and returning a list of interacting protein pairs identified by
      their Entrez Gene IDs. Specifically, such pairs represent proteins participating
      in a binary protein-protein interaction relation where the interaction is
      additionally affected by a genetic mutation-referred to as a PPIm relation. In
      this study, we explore an end-to-end approach for PPIm relation extraction by
      deploying a three-component pipeline involving deep learning-based named-entity
      recognition and relation classification models along with a knowledge-based
      approach for gene normalization. We propose several recall-focused improvements
      to our original challenge entry that placed second when matching on Entrez Gene
      ID (exact matching) and on HomoloGene ID. On exact matching, the improved system
      achieved new competitive test results of 37.78% micro-F1 with a precision of
      38.22% and recall of 37.34% that corresponds to an improvement from the prior
      best system by approximately three micro-F1 points. When matching on HomoloGene
      IDs, we report similarly competitive test results at 46.17% micro-F1 with a
      precision and recall of 46.67 and 45.59%, respectively, corresponding to an
      improvement of more than eight micro-F1 points over the prior best result. The
      code for our deep learning system is made publicly available at
      https://github.com/bionlproc/biocppi_extraction.

PMID- 30239681
TI  - PalmXplore: oil palm gene database.
AB  - A set of Elaeis guineensis genes had been generated by combining two gene
      prediction pipelines: Fgenesh++ developed by Softberry and Seqping by the
      Malaysian Palm Oil Board. PalmXplore was developed to provide a scalable data
      repository and a user-friendly search engine system to efficiently store, manage
      and retrieve the oil palm gene sequences and annotations. Information deposited
      in PalmXplore includes predicted genes, their genomic coordinates, as well as the
      annotations derived from external databases, such as Pfam, Gene Ontology and
      Kyoto Encyclopedia of Genes and Genomes. Information about genes related to
      important traits, such as those involved in fatty acid biosynthesis (FAB) and
      disease resistance, is also provided. The system offers Basic Local Alignment
      Search Tool homology search, where the results can be downloaded or visualized in
      the oil palm genome browser (MYPalmViewer). PalmXplore is regularly updated
      offering new features, improvements to genome annotation and new genomic
      sequences. The system is freely accessible at http://palmxplore.mpob.gov.my.

PMID- 30239682
TI  - PubMed Labs: an experimental system for improving biomedical literature search.
AB  - PubMed is a freely accessible system for searching the biomedical literature,
      with ~ 2.5 million users worldwide on an average workday. In order to better meet
      our users' needs in an era of information overload, we have recently developed
      PubMed Labs (www.pubmed.gov/labs), an experimental system for users to test new
      search features/tools (e.g. Best Match) and provide feedback, which enables us to
      make more informed decisions about potential changes to improve the search
      quality and overall usability of PubMed. In addition, PubMed Labs features a
      mobile-first and responsive layout that offers better support for accessing
      PubMed from increasingly popular mobiles and small-screen devices. In this paper,
      we detail PubMed Labs, its purpose, new features and best practices. We also
      encourage users to share their experience with us; based on which we are
      continuously improving PubMed Labs with more advanced features and better user
      experience.

PMID- 30239679
TI  - AgBioData consortium recommendations for sustainable genomics and genetics
      databases for agriculture.
AB  - The future of agricultural research depends on data. The sheer volume of
      agricultural biological data being produced today makes excellent data management
      essential. Governmental agencies, publishers and science funders require data
      management plans for publicly funded research. Furthermore, the value of data
      increases exponentially when they are properly stored, described, integrated and
      shared, so that they can be easily utilized in future analyses. AgBioData
      (https://www.agbiodata.org) is a consortium of people working at agricultural
      biological databases, data archives and knowledgbases who strive to identify
      common issues in database development, curation and management, with the goal of
      creating database products that are more Findable, Accessible, Interoperable and
      Reusable. We strive to promote authentic, detailed, accurate and explicit
      communication between all parties involved in scientific data. As a step toward
      this goal, we present the current state of biocuration, ontologies, metadata and
      persistence, database platforms, programmatic (machine) access to data,
      communication and sustainability with regard to data curation. Each section
      describes challenges and opportunities for these topics, along with
      recommendations and best practices.

PMID- 30239685
TI  - Validation (in Spanish) of the Mini Nutritional Assessment survey to assess the
      nutritional status of patients over 65 years of age.

PMID- 30239683
TI  - ATD: a comprehensive bioinformatics resource for deciphering the association of
      autophagy and diseases.
AB  - Autophagy is the natural, regulated, destructive mechanism of the eukaryotes cell
      that disassembles unnecessary or dysfunctional components. In recent years, the
      association between autophagy and diseases has attracted more and more attention,
      but our understanding of the molecular mechanism about the association in the
      system perspective is limited and ambiguous. Hence, we developed the
      comprehensive bioinformatics resource Autophagy To Disease (ATD,
      http://auto2disease.nwsuaflmz.com) to archive autophagy-associated diseases. This
      resource provides bioinformatics annotation system about genes and chemicals
      about autophagy and human diseases by extracting results from previous studies
      with text mining technology. Based on the big data from ATD, we found that some
      classes of disease tend to be related with autophagy, including respiratory
      disease, cancer, urogenital disease and digestive system disease. We also found
      that some classes of autophagy-related diseases have a strong association among
      each other and constitute modules. Furthermore, we extracted the autophagy
      disease-related genes (ADGs) from ATD and provided a novel algorithm Optimized
      Random Forest with Label model to predict potential ADGs. This bioinformatics
      annotation system about autophagy and human diseases may provide a basic resource
      for the further detection of the molecular mechanisms of autophagy pathway to
      disease.

PMID- 30239684
TI  - Chromosome-level genome assembly of the spotted sea bass, Lateolabrax maculatus.
AB  - Background: The spotted sea bass (Lateolabrax maculatus) is a valuable commercial
      fish that is widely cultured in China. While analyses using molecular markers and
      population genetics have been conducted, genomic resources are lacking. Findings:
      Here, we report a chromosome-scale assembly of the spotted sea bass genome by
      high-depth genome sequencing, assembly, and annotation. The genome scale was 0.67
      Gb with contig and scaffold N50 length of 31 Kb and 1,040 Kb, respectively. Hi-C
      scaffolding of the genome resulted in 24 pseudochromosomes containing 77.68% of
      the total assembled sequences. A total of 132.38 Mb repeat sequences were
      detected, accounting for 20.73% of the assembled genome. A total of 22, 015
      protein-coding genes were predicted, of which 96.52% were homologous to proteins
      in various databases. In addition, we constructed a phylogenetic tree using 1,586
      single-copy gene families and identified 125 unique gene families in the spotted
      sea bass genome. Conclusions: We assembled a spotted sea bass genome that will be
      a valuable genomic resource to understanding the biology of the spotted sea bass
      and will also lead to the development of molecular breeding techniques to
      generate spotted sea bass with better economic traits.

PMID- 30239686
TI  - Catheter-based renal denervation: the next chapter begins.

PMID- 30239688
TI  - Attitudes towards health research participation: a qualitative study of US Arabs
      and Chaldeans.
AB  - Background: The Arab Muslim and Chaldean Christian American community is unified
      by language but culturally diverse. Researchers are challenged to engage the
      Arab/Chaldean community to meet immigrant health needs. Arabs/Chaldeans are
      identified as white in clinical data sets making it difficult to identify health
      behaviours and patterns unique to the community. Objectives: To explore the views
      of members of the Arab/Chaldean community, including researchers and the lay
      public, regarding health research participation and the role of clinicians,
      researchers and community leaders in the research process. Methods: A qualitative
      study of Arab and Chaldean adults and researchers conducted in a US community
      with a large Arab/Chaldean population. Five semi-structured focus group
      discussions were triangulated with five in-depth semi-structured interviews with
      Arab or Chaldean primary care researchers. Responses were audio-recorded and
      transcribed verbatim. Transcripts were coded and thematically analysed, and
      findings confirmed with community representatives. Results: Three themes were
      identified: (i) research expectations: risks and benefits; (ii) health care
      environment: clinicians as recruiters and (iii) research participations: risks
      and benefits. Themes captured concerns with social relationships, reputation or
      trust and the cost and benefit of research participation. In the Arab/Chaldean
      community, institutional and political fears and distrust are amplified. Respect
      for physicians, teachers and faith leaders connected with or recruiting for
      studies enhances likelihood of research participation. Conclusion: Clinical
      researchers should address the cultural and immigration histories of
      Arab/Chaldean research participants. Studies that maximize trust will minimize
      participation bias and lay the groundwork for improved health. Institutional,
      sociocultural and personal factors require a pre-study phase to engage and
      educate participants.

PMID- 30239690
TI  - A laboratory competency examination in microbiology.
AB  - The American Society for Microbiology's curricular guidelines for Introductory
      Microbiology highlighted key laboratory skills in the isolation, visualization
      and identification of microorganisms as core learning objectives in the
      discipline. Since the publication of these guidelines in 2012, there has been a
      paucity of diagnostic assessment tools in the literature that can be used to
      assess competencies in the microbiology laboratory. This project aimed to
      establish a laboratory competency examination for introductory microbiology, with
      tasks specifically aligned to laboratory skills and learning outcomes outlined in
      curricular guidelines for microbiology. A Laboratory Competency Examination
      assessing student skills in light microscopy, Gram-staining, pure culture,
      aseptic technique, serial dilution, dilution calculations and pipetting was
      developed at The University of Queensland, Australia. The Laboratory Competency
      Examination was field-tested in a large introductory microbiology subject (~400
      students), and student performance and learning gains data were collected from
      2016 to 2017 to evaluate the validity of the assessment. The resulting laboratory
      assessment is presented as an endpoint diagnostic tool for assessing laboratory
      competency that can be readily adapted towards different educational contexts.

PMID- 30239689
TI  - Implications of bipolar voltage mapping and magnetic resonance imaging resolution
      in biventricular scar characterization after myocardial infarction.
AB  - Aims: We aimed to study the differences in biventricular scar characterization
      using bipolar voltage mapping compared with state-of-the-art in vivo delayed
      gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging and ex vivo T1
      mapping. Methods and results: Ten pigs with established myocardial infarction
      (MI) underwent in vivo scar characterization using LGE-CMR imaging and high
      density voltage mapping of both ventricles using a 3.5-mm tip catheter. Ex vivo
      post-contrast T1 mapping provided a high-resolution reference. Voltage maps were
      registered onto the left and right ventricular (LV and RV) endocardium, and
      epicardium of CMR-based geometries to compare voltage-derived scars with surface
      projected 3D scars. Voltage-derived scar tissue of the LV endocardium and the
      epicardium resembled surface projections of 3D in vivo and ex vivo CMR-derived
      scars using 1-mm of surface projection distance. The thinner wall of the RV was
      especially sensitive to lower resolution in vivo LGE-CMR images, in which
      differences between normalized low bipolar voltage areas and CMR-derived scar
      areas did not decrease below a median of 8.84% [interquartile range (IQR) (3.58,
      12.70%)]. Overall, voltage-derived scars and surface scar projections from in
      vivo LGE-CMR sequences showed larger normalized scar areas than high-resolution
      ex vivo images [12.87% (4.59, 27.15%), 18.51% (11.25, 24.61%), and 9.30% (3.84,
      19.59%), respectively], despite having used optimized surface projection
      distances. Importantly, 43.02% (36.54, 48.72%) of voltage-derived scar areas from
      the LV endocardium were classified as non-enhanced healthy myocardium using ex
      vivo CMR imaging. Conclusion: In vivo LGE-CMR sequences and high-density voltage
      mapping using a conventional linear catheter fail to provide accurate
      characterization of post-MI scar, limiting the specificity of voltage-based
      strategies and imaging-guided procedures.

PMID- 30239691
TI  - Corrigendum.

PMID- 30239687
TI  - beta-Cell Receptor Tyrosine Kinases in Controlling Insulin Secretion and
      Exocytotic Machinery: c-Kit and Insulin Receptor.
AB  - Insulin secretion from pancreatic beta-cells is initiated through channel
      mediated depolarization, cytoskeletal remodeling, and vesicle tethering at the
      cell membrane, all of which can be regulated through cell surface receptors.
      Receptor tyrosine kinases (RTKs) promote beta-cell development and postnatal
      signaling to improve beta-cell mass and function, yet their activation has also
      been shown to initiate exocytotic events in beta-cells. This review examines the
      role of RTK signaling in insulin secretion, with a focus on RTKs c-Kit and
      insulin receptor (IR). Pathways that control insulin release and the potential
      interplay between c-Kit and IR signaling are discussed, along with clinical
      implications of RTK therapy on insulin secretion.

PMID- 30239692
TI  - A pipeline to translate glycosaminoglycan sequences into 3D models. Application
      to the exploration of glycosaminoglycan conformational space.
AB  - Mammalian glycosaminoglycans are linear complex polysaccharides comprising
      heparan sulfate, heparin, dermatan sulfate, chondroitin sulfate, keratan sulfate
      and hyaluronic acid. They bind to numerous proteins and these interactions
      mediate their biological activities. GAG-protein interaction data reported in the
      literature are curated mostly in MatrixDB database (http://matrixdb.univ
      lyon1.fr/). However, a standard nomenclature and a machine-readable format of
      GAGs together with bioinformatics tools for mining these interaction data are
      lacking. We report here the building of an automated pipeline to (i) standardize
      the format of GAG sequences interacting with proteins manually curated from the
      literature, (ii) translate them into the machine-readable GlycoCT format and into
      SNFG (Symbol Nomenclature For Glycan) images and (iii) convert their sequences
      into a format processed by a builder generating three-dimensional structures of
      polysaccharides based on a repertoire of conformations experimentally validated
      by data extracted from crystallized GAG-protein complexes. We have developed for
      this purpose a converter (the CT23D converter) to automatically translate the
      GlycoCT code of a GAG sequence into the input file required to construct a three
      dimensional model.

PMID- 30239693
TI  - An unusual cause for implantable cardioverter-defibrillator extraction.

PMID- 30239697
TI  - Improving care at the population and individual level: lessons from SWEDEHEART.

PMID- 30239698
TI  - Volatile phenols are produced by strains of Dekkera bruxellensis under Brazilian
      fuel ethanol industry-like conditions.
AB  - Dekkera bruxellensis is a spoilage yeast in wine and fuel ethanol fermentations
      able to produce volatile phenols from hydroxycinnamic acids by the action of the
      enzymes cinnamate decarboxylase (CD) and vinyphenol reductase (VR) in wine.
      However, there is no information about this ability in the bioethanol industry.
      This work evaluated CD and VR activities and 4-ethylphenol production from p
      coumaric acid by three strains of D. bruxellensis and PE-2, an industrial
      Saccharomyces cerevisiae strain. Single and multiple-cycle batch fermentations in
      molasses and sugarcane juice were carried out. Dekkera bruxellensis strains
      showed similar CD activity but differences in VR activity. No production of 4
      ethylphenol by S. cerevisiae in any fermentation system or media was observed.
      The concentrations of 4-ethylphenol peaked during active growth of D.
      bruxellensis in single-cycle fermentation but they were lower than in multiple
      cycle fermentation. Higher concentrations were observed in molasses with molar
      conversion (p-coumaric acid to 4-ethylphenol) ranging from 45% to 85%. As the
      first report on 4-ethylphenol production in sugarcane musts by D. bruxellensis in
      industry-like conditions, it opens up a new avenue to investigate its effect on
      the viability and fermentative capacity of S. cerevisiae as well as to understand
      the interaction between the yeasts in the bioethanol industry.

PMID- 30239699
TI  - Impact of digital technologies for communicating messages on weight loss
      maintenance: a systematic literature review.
AB  - Background: Research into the use of digital technology for weight loss
      maintenance (intentionally losing at least 10% of initial body weight and
      actively maintaining it) is limited. The aim of this article was to
      systematically review randomized controlled trials (RCTs) reporting on the use of
      digital technologies for communicating on weight loss maintenance to determine
      its' effectiveness, and identify gaps and areas for further research. Methods: A
      systematic literature review was conducted by searching electronic databases to
      locate publications dated between 2006 and February 2018. Criteria were applied,
      and RCTs using digital technologies for weight loss maintenance were selected.
      Results: Seven RCTs were selected from a total of 6541 hits after de-duplication
      and criteria applied. Three trials used text messaging, one used e-mail, one used
      a web-based system and two compared such a system with face-to-face contact. From
      the seven RCTs, one included children (n = 141) and reported no difference in BMI
      Standard Deviation between groups. From the seven trials, four reported that
      technology is effective for significantly aiding weight loss maintenance compared
      with control (no contact) or face-to face-contact in the short term (between 3
      and 24 months). Conclusions: It was concluded that digital technologies have the
      potential to be effective communication tools for significantly aiding weight
      loss maintenance, especially in the short term (from 3 to 24 months). Further
      research is required into the long-term effectiveness of contemporary
      technologies.

PMID- 30239696
TI  - Evolution of Olfactory Functions on the Fire Ant Social Chromosome.
AB  - Understanding the molecular evolutionary basis of social behavior is a major
      challenge in evolutionary biology. Social insects evolved a complex language of
      chemical signals to coordinate thousands of individuals. In the fire ant
      Solenopsis invicta, chemical signals are involved in the determination of a
      polymorphic social organization. Single-queen (monogyne) or multiqueen (polygyne)
      social structure is determined by the "social chromosome," a nonrecombining
      region containing ~504 genes with two distinct haplotypes, SB and Sb. Monogyne
      queens are always SBB, while polygyne queens are always SBb. Workers discriminate
      monogyne from polygyne queens based on olfactory cues. Here, we took an
      evolutionary genomics approach to search for candidate genes in the social
      chromosome that could be responsible for this discrimination. We compared the SB
      and Sb haplotypes and analyzed the evolutionary rates since their divergence.
      Notably, we identified a cluster of 23 odorant receptors in the nonrecombining
      region of the social chromosome that stands out in terms of nonsynonymous changes
      in both haplotypes. The cluster includes twelve genes formed by recent Solenopsis
      specific duplications. We found evidence for positive selection on several tree
      branches and significant differences between the SB and Sb haplotypes of these
      genes. The most dramatic difference is the complete deletion of two of these
      genes in Sb. These results suggest that the evolution of polygyne social
      organization involved adaptations in olfactory genes and opens the way for
      functional studies of the molecular mechanisms underlying social behavior.

PMID- 30239695
TI  - Factors Influencing Gene Family Size Variation Among Related Species in a Plant
      Family, Solanaceae.
AB  - Gene duplication and loss contribute to gene content differences as well as
      phenotypic divergence across species. However, the extent to which gene content
      varies among closely related plant species and the factors responsible for such
      variation remain unclear. Here, using the Solanaceae family as a model and Pfam
      domain families as a proxy for gene families, we investigated variation in gene
      family sizes across species and the likely factors contributing to the variation.
      We found that genes in highly variable families have high turnover rates and tend
      to be involved in processes that have diverged between Solanaceae species,
      whereas genes in low-variability families tend to have housekeeping roles. In
      addition, genes in high- and low-variability gene families tend to be duplicated
      by tandem and whole genome duplication, respectively. This finding together with
      the observation that genes duplicated by different mechanisms experience
      different selection pressures suggest that duplication mechanism impacts gene
      family turnover. We explored using pseudogene number as a proxy for gene loss but
      discovered that a substantial number of pseudogenes are actually products of
      pseudogene duplication, contrary to the expectation that most plant pseudogenes
      are remnants of once-functional duplicates. Our findings reveal complex
      relationships between variation in gene family size, gene functions, duplication
      mechanism, and evolutionary rate. The patterns of lineage-specific gene family
      expansion within the Solanaceae provide the foundation for a better understanding
      of the genetic basis underlying phenotypic diversity in this economically
      important family.

PMID- 30239700
TI  - Towards biobased industry: acetate as a promising feedstock to enhance the
      potential of microbial cell factories.
AB  - A broad range of different chemical and pharmaceutical compounds have been
      produced in microbial cell factories. To compete with traditional crude oil based
      production processes, the use of complex alternative raw materials such as
      lignocellulosic biomass, waste streams and utilization of CO2 in gas
      fermentations has been suggested. All of these streams contain acetate, a cheap
      and potentially interesting carbon source for microbial production processes.
      Acetate (co-)utilization remains challenging, which is the reason for extensive
      research on the use of acetate for the production of value-added compounds. For
      industrial implementation of microbial conversion processes using acetate as a
      feedstock gaining a deeper insight into acetate metabolism of microorganisms is
      essential. Systems level analyses and manipulation of potential host organisms
      should be applied to achieve full utilization of this prospective substrate.

PMID- 30239701
TI  - Identification of key amino acid residues determining ligand binding specificity,
      homodimerization and cellular distribution of human Galectin-10.
AB  - Charcot-Leyden crystal protein/Gal-10, abundantly expressed in eosinophils and
      basophils, is related to several immune diseases. Recently, crystallographic and
      biochemical studies showed that Gal-10 cannot bind lactose, because a glutamate
      residue (Glu33) from another monomer blocks the binding site. Moreover, Gal-10
      actually forms a novel dimeric structure compared to other galectins. To
      investigate the role that Glu33 plays in inhibiting lactose binding, we mutated
      this residue to glutamine, aspartate, and alanine. The structure of E33A shows
      that Gal-10 can now bind lactose. In the hemagglutination assay, lactose could
      inhibit E33A from inducing chicken erythrocyte agglutination. Furthermore, we
      identified a tryptophan residue (Trp127) at the interface of homodimer that is
      crucial for Gal-10 dimerization. The variant W127A, which exists as a monomer,
      exhibited higher hemagglutination activity than wild type Gal-10. The solid phase
      assay also showed that W127A could bind to lactose-modified sepharose-6B, whereas
      wild type Gal-10 could not. This indicates that the open carbohydrate binding
      site of the W127A monomer can bind to lactose. In addition, the distribution of
      EGFP-tagged Gal-10 and its variants in HeLa cells was investigated. Because Trp72
      is the highly conserved in the ligand binding sites of galectins, we used EGFP
      tagged W72A to show that Gal-10 could not be transported into the nucleus,
      indicating that Trp72 is crucial for Gal-10 transport into that organelle.

PMID- 30239704
TI  - Extensive evaluation of the generalized relevance network approach to inferring
      gene regulatory networks.
AB  - Background: The generalized relevance network approach to network inference
      reconstructs network links based on the strength of associations between data in
      individual network nodes. It can reconstruct undirected networks, i.e., relevance
      networks, sensu stricto, as well as directed networks, referred to as causal
      relevance networks. The generalized approach allows the use of an arbitrary
      measure of pairwise association between nodes, an arbitrary scoring scheme that
      transforms the associations into weights of the network links, and a method for
      inferring the directions of the links. While this makes the approach powerful and
      flexible, it introduces the challenge of finding a combination of components that
      would perform well on a given inference task. Results: We address this challenge
      by performing an extensive empirical analysis of the performance of 114 variants
      of the generalized relevance network approach on 47 tasks of gene network
      inference from time-series data and 39 tasks of gene network inference from
      steady-state data. We compare the different variants in a multi-objective manner,
      considering their ranking in terms of different performance metrics. The results
      suggest a set of recommendations that provide guidance for selecting an
      appropriate variant of the approach in different data settings. Conclusions: The
      association measures based on correlation, combined with a particular scoring
      scheme of asymmetric weighting, lead to optimal performance of the relevance
      network approach in the general case. In the two special cases of inference tasks
      involving short time-series data and/or large networks, association measures
      based on identifying qualitative trends in the time series are more appropriate.

PMID- 30239703
TI  - Preparation and Planning for Future Care in the Deep South: Adapting a Validated
      Tool for Cultural Sensitivity.
AB  - Background and Objectives: This study describes the adaptation and validation of
      Sorensen et al. (2017)'s preparation for future care (PFC) scale with diverse
      samples including rural dwelling African Americans and certified nursing
      assistants (CNAs), and subsequent psychometric development. Research Design and
      Methods: Responses to the five-subscale PFC survey from 33 rural African American
      men across 12 months and cognitive interviews with a subset of 12 of these men
      are described. Psychometric refinement included descriptive qualitative analyses
      of consultations with experienced lay research advisors (N = 4 and N = 7)
      regarding potential changes to the PFC and a confirmatory factor analysis of the
      resultant scale (N = 138). Results: Cognitive interviews with rural African
      American men revealed difficulty understanding Eurocentric questions. Emergent
      themes included emotional avoidance of planning, considerations of nursing homes
      and possible care providers, and coping strategies. In two consultation meetings,
      trained lay research advisors recommended language modifications to the original
      questions and response options. Factor analyzing the resultant scale revealed
      support for the original subscale constructs (acceptable fit: chi2 = 205.03, df =
      124, p < .001; root mean square error of approximation = .069 [.052-.085];
      comparative fit index = .93; Tucker-Lewis index = .91). Discussion and
      Implications: PFC and engagement in advance care planning is uncommon among
      African Americans, possibly due to distrust of and lack of cultural competency
      among health care professionals. The resulting tool and response options may be
      used as an interview guide/survey with African Americans to gain understanding
      about their preparation for future health care needs.

PMID- 30239705
TI  - Uterine stem cells: from basic research to advanced cell therapies.
AB  - BACKGROUND: Stem cell research in the endometrium and myometrium from animal
      models and humans has led to the identification of endometrial/myometrial stem
      cells and their niches. This basic knowledge is beginning to be translated to
      clinical use for incurable uterine pathologies. Additionally, the implication of
      bone marrow-derived stem cells (BMDSCs) in uterine physiology has opened the
      field for the exploration of an exogenous and autologous source of stem cells.
      OBJECTIVE AND RATIONALE: In this review, we outline the progress of endometrial
      and myometrial stem/progenitor cells in both human and mouse models from their
      characterization to their clinical application, indicating roles in Asherman
      syndrome, atrophic endometrium and tissue engineering, among others. SEARCH
      METHODS: A comprehensive search of PubMed and Google Scholar up to December 2017
      was conducted to identify peer-reviewed literature related to the contribution of
      bone marrow, endometrial and myometrial stem cells to potential physiological
      regeneration as well as their implications in pathologies of the human uterus.
      OUTCOMES: The discovery and main characteristics of stem cells in the murine and
      human endometrium and myometrium are presented together with the relevance of
      their niches and cross-regulation. The current state of advanced stem cell
      therapy using BMDSCs in the treatment of Asherman syndrome and atrophic
      endometrium is analyzed. In the myometrium, the understanding of genetic and
      epigenetic defects that result in the development of tumor-initiating cells in
      the myometrial stem niche and thus contribute to the growth of uterine leiomyoma
      is also presented. Finally, recent advances in tissue engineering based on the
      creation of novel three-dimensional scaffolds or decellularisation open up new
      perspectives for the field of uterine transplantation. WIDER IMPLICATIONS: More
      than a decade after their discovery, the knowledge of uterine stem cells and
      their niches is crystalising into novel therapeutic approaches aiming to treat
      with cells those conditions that cannot be cured with drugs, particularly the
      currently incurable uterine pathologies. Additional work and improvements are
      needed, but the basis has been formed for this therapeutic application of uterine
      cells.

PMID- 30239702
TI  - Genomic Landscape of Methylation Islands in Hymenopteran Insects.
AB  - Recent genome-wide DNA methylation analyses of insect genomes accentuate an
      intriguing contrast compared with those in mammals. In mammals, most CpGs are
      heavily methylated, with the exceptions of clusters of hypomethylated sites
      referred to as CpG islands. In contrast, DNA methylation in insects is localized
      to a small number of CpG sites. Here, we refer to clusters of methylated CpGs as
      "methylation islands (MIs)," and investigate their characteristics in seven
      hymenopteran insects with high-quality bisulfite sequencing data. Methylation
      islands were primarily located within gene bodies. They were significantly
      overrepresented in exon-intron boundaries, indicating their potential roles in
      splicing. Methylated CpGs within MIs exhibited stronger evolutionary conservation
      compared with those outside of MIs. Additionally, genes harboring MIs exhibited
      higher and more stable levels of gene expression compared with those that do not
      harbor MIs. The effects of MIs on evolutionary conservation and gene expression
      are independent and stronger than the effect of DNA methylation alone. These
      results indicate that MIs may be useful to gain additional insights into
      understanding the role of DNA methylation in gene expression and evolutionary
      conservation in invertebrate genomes.

PMID- 30239707
TI  - Assessment of viral and bacterial contamination of fresh and ripened semi-hard
      cheeses.
AB  - This study aimed to evaluate viral and bacterial contamination from typical
      Brazilian cheeses, such as Minas (fresh) and Prato (ripened), commercially
      obtained in the Greater Metropolitan Region of the State of Rio de Janeiro,
      Brazil. Minas [30], Prato [30] and sliced Prato [30] cheese samples were
      investigated for norovirus genogroup I and II (NoV GI-II) and human adenovirus
      (HAdV) by direct nucleic acid extraction using TRIzol and amplification by TaqMan
      based quantitative polymerase chain reaction. Listeria monocytogenes, Salmonella
      spp., coagulase-positive staphylococci (CPS) and fecal coliforms were also
      assessed by using standard counting methods. NoV GI and GII were detected in one
      sample (1.1%) each and HAdV in nine samples (10.0%) while bacteriological
      analysis revealed five samples (5.5%) contaminated with L. monocytogenes, 27
      (30.0%) with fecal coliforms and 10 (11.1%) with CPS. Salmonella spp. was not
      detected in any sample. Viruses were detected in 11 samples (12.2%), of which 9
      met the microbiological criteria used to evaluate the microbiological quality of
      the cheeses, stressing the importance of considering virological parameters for
      monitoring this food matrix.

PMID- 30239706
TI  - Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural
      differentiation.
AB  - Background: Investigating cell fate decision and subpopulation specification in
      the context of the neural lineage is fundamental to understanding neurogenesis
      and neurodegenerative diseases. The differentiation process of neural-tube-like
      rosettes in vitro is representative of neural tube structures, which are composed
      of radially organized, columnar epithelial cells and give rise to functional
      neural cells. However, the underlying regulatory network of cell fate commitment
      during early neural differentiation remains elusive. Results: In this study, we
      investigated the genome-wide transcriptome profile of single cells from six
      consecutive reprogramming and neural differentiation time points and identified
      cellular subpopulations present at each differentiation stage. Based on the
      inferred reconstructed trajectory and the characteristics of subpopulations
      contributing the most toward commitment to the central nervous system lineage at
      each stage during differentiation, we identified putative novel transcription
      factors in regulating neural differentiation. In addition, we dissected the
      dynamics of chromatin accessibility at the neural differentiation stages and
      revealed active cis-regulatory elements for transcription factors known to have a
      key role in neural differentiation as well as for those that we suggest are also
      involved. Further, communication network analysis demonstrated that cellular
      interactions most frequently occurred in the embryoid body stage and that each
      cell subpopulation possessed a distinctive spectrum of ligands and receptors
      associated with neural differentiation that could reflect the identity of each
      subpopulation. Conclusions: Our study provides a comprehensive and integrative
      study of the transcriptomics and epigenetics of human early neural
      differentiation, which paves the way for a deeper understanding of the regulatory
      mechanisms driving the differentiation of the neural lineage.

PMID- 30239710
TI  - Extracorporeal cardiopulmonary support in acute high-risk pulmonary embolism:
      still waiting for solid evidence.

PMID- 30239708
TI  - Ancient Endogenous Pararetroviruses in Oryza Genomes Provide Insights into the
      Heterogeneity of Viral Gene Macroevolution.
AB  - Endogenous viral sequences in eukaryotic genomes, such as those derived from
      plant pararetroviruses (PRVs), can serve as genomic fossils to study viral
      macroevolution. Many aspects of viral evolutionary rates are heterogeneous,
      including substitution rate differences between genes. However, the evolutionary
      dynamics of this viral gene rate heterogeneity (GRH) have been rarely examined.
      Characterizing such GRH may help to elucidate viral adaptive evolution. In this
      study, based on robust phylogenetic analysis, we determined an ancient endogenous
      PRV group in Oryza genomes in the range of being 2.41-15.00 Myr old. We
      subsequently used this ancient endogenous PRV group and three younger groups to
      estimate the GRH of PRVs. Long-term substitution rates for the most conserved
      gene and a divergent gene were 2.69 * 10-8 to 8.07 * 10-8 and 4.72 * 10-8 to 1.42
      * 10-7 substitutions/site/year, respectively. On the basis of a direct
      comparison, a long-term GRH of 1.83-fold was identified between these two genes,
      which is unexpectedly low and lower than the short-term GRH (>3.40-fold) of PRVs
      calculated using published data. The lower long-term GRH of PRVs was due to the
      slightly faster rate decay of divergent genes than of conserved genes during
      evolution. To the best of our knowledge, we quantified for the first time the
      long-term GRH of viral genes using paleovirological analyses, and proposed that
      the GRH of PRVs might be heterogeneous on time scales (time-dependent GRH). Our
      findings provide special insights into viral gene macroevolution and should
      encourage a more detailed examination of the viral GRH.

PMID- 30239709
TI  - Assessing the Performance of Ks Plots for Detecting Ancient Whole Genome
      Duplications.
AB  - Genomic data have provided evidence of previously unknown ancient whole genome
      duplications (WGDs) and highlighted the role of WGDs in the evolution of many
      eukaryotic lineages. Ancient WGDs often are detected by examining distributions
      of synonymous substitutions per site (Ks) within a genome, or "Ks plots." For
      example, WGDs can be detected from Ks plots by using univariate mixture models to
      identify peaks in Ks distributions. We performed gene family simulation
      experiments to evaluate the effects of different Ks estimation methods and
      mixture models on our ability to detect ancient WGDs from Ks plots. The
      simulation experiments, which accounted for variation in substitution rates and
      gene duplication and loss rates across gene families, tested the effects of WGD
      age and gene retention rates following WGD on inferring WGDs from Ks plots. Our
      simulations reveal limitations of Ks plot analyses. Strict interpretations of
      mixture model analyses often overestimate the number of WGD events, and Ks plot
      analyses typically fail to detect WGDs when <=10% of the duplicated genes are
      retained following the WGD. However, WGDs can accurately be characterized over an
      intermediate range of Ks. The simulation results are supported by empirical
      analyses of transcriptomic data, which also suggest that biases in gene retention
      likely affect our ability to detect ancient WGDs. Although our results indicate
      mixture model results should be interpreted with great caution, using node
      averaged Ks estimates and applying more appropriate mixture models can improve
      the accuracy of detecting WGDs.

PMID- 30239712
TI  - How Can Autonomy Be Maintained and Informal Care Improved for People With
      Dementia Living in Residential Care Facilities: A Systematic Literature Review.
AB  - Background and Objectives: For people with dementia living in residential care
      facilities, maintaining autonomy and receiving informal care are important. The
      objective of this review is to understand how caregiving approaches and physical
      environment, including technologies contribute to the maintenance of autonomy and
      informal care provision for this population. Research Design and Methods: A
      literature review of peer-reviewed articles published between January 1995 and
      July 2017 was performed. Realist logic of analysis was used, involving context,
      mechanism and outcome configurations. Results: Forty-nine articles were included.
      The improvement of the relationship between residents and formal/informal
      caregivers is important. This increases the knowledge (sharing) about the
      resident and contributes to their autonomy. A social, flexible, and welcoming
      attitude of the formal caregiver improves the provision of informal care.
      Specially designed spaces, for instance, therapeutic gardens, create activities
      for residents that remind them of themselves and contribute to their autonomy.
      Use of technologies reduces caregiver's time for primary tasks and therefore
      enables secondary tasks such as interaction with the residents. Discussion and
      Implications: The results revealed how residential care facilities could maintain
      autonomy of their residents and improve informal care delivery using caregiving
      approaches and the physical environment including technologies. The results are
      supporting toward each other in maintaining autonomy and also helped in enhancing
      informal care provision. For residential care facilities that want to maintain
      the autonomy of their residents and improve informal care delivery, it is
      important to pay attention to all aspects of living in a residential care
      facility.

PMID- 30239711
TI  - Modes and timing of death in 66 252 patients with non-ST-segment elevation acute
      coronary syndromes enrolled in 14 TIMI trials.
AB  - Aims: Although presenting features and early sequelae of non-ST-segment elevation
      acute coronary syndromes (NSTE-ACS) are well described, less is known about
      longer-term risks and modes of death. The purpose of this study was to
      characterize modes of death following NSTE-ACS in clinical trial populations.
      Methods and results: We evaluated 66 252 patients with NSTE-ACS enrolled in 14
      Thrombolysis in Myocardial Infarction (TIMI) trials, examining baseline
      characteristics and modes and timing of death. Of the 66 252 patients followed
      for a median of 372 (interquartile range 218-521) days, 3147 (4.8%) died by the
      time of last follow-up. Of the 2606 patients (82.8%) with known modes of death,
      75.1% were related to a cardiovascular (CV) event, 3.0% were related to a
      bleeding event (including intracranial haemorrhage), and 21.8% were related to a
      non-CV/non-bleeding event. The most common modes of CV death were sudden death
      (SD) and recurrent myocardial infarction (MI) (36.4% and 23.4%, respectively, of
      CV deaths). The proportion of CV deaths related to recurrent MI was higher in the
      first 30 days than it was after 30 days following NSTE-ACS (30.6% vs. 18.7%),
      whereas the proportion of SD was lower in the first 30 days than after 30 days
      (21.6% vs. 46.2%). Conclusion: Sudden death represents the largest proportion of
      CV deaths after 30 days among patients enrolled in CV clinical trials with NSTE
      ACS. Further investigations aimed at defining the epidemiology of SD and
      developing specific therapies and management approaches to reduce SD following
      NSTE-ACS may be critical to reducing late mortality.

PMID- 30239714
TI  - Antirestriction activities of KlcA (RP4) and ArdB (R64) proteins.
AB  - Antirestriction proteins of the ArdB group (ArdB, KlcA) specifically inhibit
      restriction (endonuclease) activity of restriction-modification (RM) type I
      systems. Antirestriction activity of KlcA and ArdB, encoded in transmissible
      plasmids RP4 (IncPalpha) and R64 (IncI1), respectively, has been determined. We
      show that the protein KlcA (RP4), an amino acid sequence identical to that of the
      protein KlcA (RK2), inhibits the activity of EcoKI when the klcA gene is located
      on the plasmid under the control of strong promoter. It was demonstrated that
      proteins KlcA (RP4) and ArdB (R64) are characterized by approximately equal
      antirestriction activity. Analysis of amino acid sequences of ArdB homologs
      revealed four groups of conserved amino acids located on the surface of the
      protein globule: (1) R16, E32, W51; (2) Y46, G48; (3) S84, D86, E132 and (4) N77,
      L140, D141. It was shown that substitution of polar amino acids to hydrophobic A
      and L leads to a significant decrease in the ArdB antirestriction activity level
      (approximately 100-fold). A conserved region forming a 'ring belt' on the globule
      surface consisting of E32, S84, E132, and both N77 and D141 as the 'key section'
      of ArdB/KlcA was identified.

PMID- 30239715
TI  - Is the modified single-patch repair superior to the double-patch repair of
      complete atrioventricular septal defects?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was, 'Is the modified single-patch repair
      superior to the double-patch repair of complete atrioventricular septal
      defects?'. A total of 634 papers were found using the reported search, of which 9
      represented the best evidence to answer the clinical question, which included 1
      meta-analysis and 8 cohort studies. The authors, journal, date and country of
      publication, patient group studied, study type, relevant outcomes and results of
      these papers were tabulated. There was limited high-quality evidence available,
      with all the included studies being retrospective and observational in nature.
      One meta-analysis and 8 cohort studies provided evidence that there was no
      significant difference in survival or other postoperative outcomes based on a
      surgical technique during follow-up ranging from 6 months to 4.2 years. Surgical
      reintervention for development of left ventricular outflow tract obstruction,
      left atrioventricular valve dysfunction or residual septal defects after the
      initial repair of complete atrioventricular septal defect was not significantly
      different between cohorts in almost all studies. Cardiopulmonary bypass and
      aortic cross-clamp times were significantly shorter with the modified single
      patch repair compared to the double-patch repair in all studies that examined
      these variables, but this did not correspond to a difference in outcomes. We
      conclude, based on the available evidence, that the modified single-patch repair
      of complete atrioventricular septal defect is similar to the double-patch repair
      in terms of postoperative outcomes. However, this conclusion is limited by the
      retrospective nature of all studies, small cohort sizes and short durations of
      follow-up in addition to lack of statistical analysis in 1 study.

PMID- 30239713
TI  - Thermosipho spp. Immune System Differences Affect Variation in Genome Size and
      Geographical Distributions.
AB  - Thermosipho species inhabit thermal environments such as marine hydrothermal
      vents, petroleum reservoirs, and terrestrial hot springs. A 16S rRNA phylogeny of
      available Thermosipho spp. sequences suggested habitat specialists adapted to
      living in hydrothermal vents only, and habitat generalists inhabiting oil
      reservoirs, hydrothermal vents, and hotsprings. Comparative genomics of 15
      Thermosipho genomes separated them into three distinct species with different
      habitat distributions: The widely distributed T. africanus and the more
      specialized, T. melanesiensis and T. affectus. Moreover, the species can be
      differentiated on the basis of genome size (GS), genome content, and immune
      system composition. For instance, the T. africanus genomes are largest and
      contained the most carbohydrate metabolism genes, which could explain why these
      isolates were obtained from ecologically more divergent habitats. Nonetheless,
      all the Thermosipho genomes, like other Thermotogae genomes, show evidence of
      genome streamlining. GS differences between the species could further be
      correlated to differences in defense capacities against foreign DNA, which
      influence recombination via HGT. The smallest genomes are found in T. affectus
      that contain both CRISPR-cas Type I and III systems, but no RM system genes. We
      suggest that this has caused these genomes to be almost devoid of mobile
      elements, contrasting the two other species genomes that contain a higher
      abundance of mobile elements combined with different immune system
      configurations. Taken together, the comparative genomic analyses of Thermosipho
      spp. revealed genetic variation allowing habitat differentiation within the genus
      as well as differentiation with respect to invading mobile DNA.

PMID- 30239716
TI  - New Perspectives on the Evolutionary History of Vitellogenin Gene Family in
      Vertebrates.
AB  - Vitellogenin (Vtg) is a glycolipophosphoprotein produced by oviparous and
      ovoviviparous species and is the precursor protein of the yolk, an essential
      nutrient reserve for embryonic development and early larval stages. Vtg is
      encoded by a family of paralog genes whose number varies in the different
      vertebrate lineages. Its evolution has been the subject of considerable analyses
      but it remains still unclear. In this work, microsyntenic and phylogenetic
      analyses were performed in order to increase our knowledge on the evolutionary
      history of this gene family in vertebrates. Our results support the hypothesis
      that the vitellogenin gene family is expanded from two genes both present at the
      beginning of vertebrate radiation through multiple independent duplication events
      occurred in the diverse lineages.

PMID- 30239717
TI  - Loss of CRB2 in Muller glial cells modifies a CRB1-associated retinitis
      pigmentosa phenotype into a Leber congenital amaurosis phenotype.
AB  - Variations in the human Crumbs homolog-1 (CRB1) gene lead to an array of retinal
      dystrophies including early-onset of retinitis pigmentosa (RP) and Leber
      congenital amaurosis (LCA) in children. To investigate the physiological roles of
      CRB1 and CRB2 in retinal Muller glial cells, we analysed mouse retinas lacking
      both proteins in Muller glial cells. The peripheral retina showed a faster
      progression of dystrophy than the central retina. The central retina showed
      retinal folds, disruptions at the outer limiting membrane, protrusion of
      photoreceptor nuclei into the inner and outer segment layers, and ingression of
      photoreceptor nuclei into the photoreceptor synaptic layer. The peripheral retina
      showed a complete loss of the photoreceptor synapse layer, intermingling of
      photoreceptor nuclei within the inner nuclear layer and ectopic photoreceptor
      cells in the ganglion cell layer. Electroretinography showed severe attenuation
      of the scotopic a-wave at 1 month of age with responses below detection levels at
      3-months of age. The double knockout mouse retinas mimicked a phenotype
      equivalent to a clinical LCA phenotype due to loss of CRB1. Localization of CRB1
      and CRB2 in non-human primate retinas was analyzed at the ultrastructural level.
      We found that non-human primate CRB1 and CRB2 proteins localized to the subapical
      region adjacent to adherens junctions at the outer limiting membrane in Muller
      glial cells and photoreceptors. Our data suggest that loss of CRB2 in Muller
      glial cells aggravates the CRB1-associated RP-like phenotype towards an LCA-like
      phenotype.

PMID- 30239718
TI  - Inconclusive chromosomal assessment after blastocyst biopsy: prevalence,
      causative factors and outcomes after re-biopsy and re-vitrification. A
      multicenter experience.
AB  - STUDY QUESTION: Can a second round of biopsy, vitrification and chromosomal
      testing provide a valid diagnosis where the first attempt fails? SUMMARY ANSWER:
      The risk of inconclusive chromosomal-assessment after trophectoderm biopsy was
      2.5% but a further biopsy and vitrification-warming appeared not to impair the
      competence of euploid blastocysts. WHAT IS KNOWN ALREADY: The increasing
      implementation of multicell trophectoderm biopsy has significantly reduced the
      risk of inconclusive diagnosis after preimplantation-genetic-testing (PGT). Yet,
      few reports have defined the variables that influence the risk of failure or
      described the technical and clinical outcomes after re-biopsy. STUDY DESIGN,
      SIZE, DURATION: Retrospective multicenter study involving 8990 blastocyst
      biopsies conducted between April 2013 and September 2017 at six IVF centers but
      analyzed at a single genetic laboratory. A total of 206 blastocysts were
      successfully re-biopsied after warming and re-expansion, then re-vitrified. And
      49 of these blastocysts were diagnosed euploid and used in single-embryo
      transfers (SETs). Logistic regression analyses were conducted.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 3244 PGT-for-aneuploidies
      (PGT-A) cycles with a freeze-all approach, vitrification and qPCR-based analysis
      were performed by 2687 consenting couples. DNA amplification failure (AF) or non
      concurrent data resulted in inconclusive diagnoses. In case of DNA amplification,
      the cellularity of the biopsy was estimated according to a previously validated
      method. Euploid SETs were performed. Clinical pregnancy, miscarriage, live birth
      rates (LBR) and perinatal outcomes were monitored. MAIN RESULTS AND THE ROLE OF
      CHANCE: Overall, 2.5% of trophectoderm biopsies resulted in an inconclusive
      diagnosis (N = 228/8990). Specifically, 2% (N = 176/8990) resulted in AF and 0.5%
      (N = 52/8990) in non-concurrent results. The only parameters significantly
      associated with inconclusive diagnoses were the IVF center and the embryo age
      (days) at biopsy. Among samples with successful amplification, the number of
      cells in the biopsy and the day of biopsy were critical to limit non-concurrent
      results. In total, 213 blastocysts with an inconclusive diagnosis were warmed for
      re-analysis and the survival rate was 96.7% (N = 206/213). The euploidy rate in
      blastocysts biopsied twice was 51.9% (N = 107/206) and the euploid embryos were
      re-vitrified. Overall, 49 euploid embryos were warmed for replacement and all
      survived. The LBR after SET was 38.8% (N = 19/49). No minor/major
      obstetrical/perinatal complication was reported. LIMITATIONS, REASONS FOR
      CAUTION: A single aneuploidy-testing method was adopted in this retrospective
      analysis. A more powered report of the clinical and obstetrical/perinatal
      outcomes after re-biopsied and re-vitrified blastocysts euploid SET requires a
      larger sample size. WIDER IMPLICATIONS OF THE FINDINGS: It is important to re
      biopsy and re-vitrify undiagnosed blastocysts since healthy live births can
      result from them. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION
      NUMBER: None.

PMID- 30239719
TI  - Mitochondrial division inhibitor 1 reduces dynamin-related protein 1 and
      mitochondrial fission activity.
AB  - The purpose of our study was to better understand the effects of mitochondrial
      division inhibitor 1 (Mdivi-1) on mitochondrial fission, mitochondrial
      biogenesis, electron transport activities, and cellular protection. In recent
      years, researchers have found excessive mitochondrial fragmentation and reduced
      fusion in a large number of diseases with mitochondrial dysfunction. Therefore,
      several groups have developed mitochondrial division inhibitors. Among these,
      Mdivi-1 was extensively studied and was found to reduce Drp1 levels and excessive
      mitochondrial fission, enhance mitochondrial fusion activity and protect cells.
      However, a recent study by Bordt et al. (2017) (1) questioned earlier findings of
      the beneficial, inhibiting effects of Mdivi-1. In the current study, we studied
      the protective effects of Mdivi-1 by studying the following: mRNA and protein
      levels of electron transport chain (ETC) genes, mitochondrial dynamics and
      biogenesis genes, enzymatic activities of ETC complexes I, II, III and IV, the
      mitochondrial network, mitochondrial size & number, Drp1 GTPase enzymatic
      activity and mitochondrial respiration 1) in N2a cells treated with Mdivi-1, 2)
      overexpressed with full-length Drp1+Mdivi-1-treated N2a cells and 3) Drp1 RNA
      silenced+Mdivi-1-treated N2a cells. We found reduced levels of the fission genes
      Drp1 and Fis1 levels; increased levels of the fusion genes Mfn1, Mfn2, and Opa1;
      and the biogenesis genes PGC1alpha, Nrf1, Nrf2, and TFAM. Increased levels mRNA
      and protein levels were found in ETC genes of complexes I, II and IV genes.
      Immunoblotting data agreed with mRNA changes. Transmission electron microscopy
      analysis revealed reduced numbers of mitochondria and increased length of
      mitochondria 1) in N2a cells treated with Mdivi-1, 2) cells overexpressed with
      full-length Drp1+ Mdivi-1-treated N2a cells and 3) Drp1 RNA silenced+Mdivi-1
      treated N2a cells. Immunofluorescence analysis revealed that mitochondrial
      network was increased. Increased levels of complex I, II and IV enzymatic
      activities were found in all 3 groups of cells treated with low concentration of
      Mdivi-1. Mitochondrial function was increased and GTPase-Drp1 activity was
      decreased in all 3 groups of N2a cells. These observations strongly suggest that
      Mdivi-1 is a Drp1 inhibitor and directly reduces mitochondrial fragmentation and
      further, Mdivi-1 is a promising molecule to treat human diseases with ETC
      complexes, I, II and IV.

PMID- 30239720
TI  - Modeling Cornelia de Lange Syndrome in vitro and in vivo reveals a role for
      cohesin complex in neuronal survival and differentiation.
AB  - Cornelia de Lange Syndrome (CdLS), which is reported to affect about 1 in 10,000
      to 30,000 newborns, is a multisystem organ developmental disorder with relatively
      mild to severe effects. Among others, intellectual disability represents an
      important feature of this condition.Cornelia de Lange syndrome can result from
      mutations in at least five genes: NIPBL (nipped-B-like protein), SMC1A
      (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of
      chromosomes 3), RAD21 (RAD21 Cohesin Complex Component), and HDAC8 (Histone
      deacetylase 8). It is believed that mutations in these genes cause CdLS by
      impairing the function of the cohesin complex (to which all the aforementioned
      genes contribute to the structure or function), disrupting gene regulation during
      critical stages of early development.Since intellectual disorder might result
      from alterations in neural development, in this work, we studied the role of
      Hdac8 gene in mouse neural stem cells and in vertebrate (D.rerio) brain
      development by knock-down and chemical inhibition experiments. An underlying
      features of Hdac8 deficiency is an increased cell death in the developing neural
      tissues, either in mouse NSCs and in zebrafish embryos.

PMID- 30239723
TI  - Cell-lineage specificity of primary cilia during postnatal epididymal
      development.
AB  - STUDY QUESTION: Where are primary cilia (PC) organelles located during postnatal
      epididymal development? SUMMARY ANSWER: Our findings unveil the existence of PC
      sensory organelles in different epididymal cell types according to postnatal
      development stage. WHAT IS KNOWN ALREADY: Primary cilia are sensory organelles
      that orchestrate major signaling pathways during organ development and
      homeostasis. Epididymal PC have been detected in the horses, donkey and mules but
      their cell-lineage specificity has never been investigated in this organ. STUDY
      DESIGN, SIZE, DURATION: A longitudinal study was performed by examining tissue
      from n = 3 to n = 10 transgenic mice at different times of postnatal development.
      Tissues were fixed by intracardiac perfusion and the epididymides collected.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Transmission electron microscopy and
      confocal microscopy/3D reconstruction were used on a double transgenic mouse
      model expressing endogenous fluorescence in PC and centrioles (Arl13b
      mCherry/Centrin2-GFP). Several PC parameters (i.e. length, orientation relative
      to the lumen) were quantified by using an image-processing pipeline. Epididymal
      tissues and serum-free cultures of DC2 immortalized epididymal principal murine
      cell lines were used to identify primary ciliary signaling components. MAIN
      RESULTS AND THE ROLE OF CHANCE: We report here a constitutive localization of PC
      in peritubular myoid cells and a dynamic profiling in epithelial cells throughout
      postnatal epididymal development. While PC are present at the apical pole of the
      undifferentiated epithelial cells from birth to puberty, they are absent from the
      apical pole of the epithelium in adults, where they appear exclusively associated
      with cytokeratin 5-positive basal cells. We determined that PC from epididymal
      cells are associated with polycystin 1 (PC1), polycystin 2 (PC2), and Gli-3
      Hedgehog signaling transcription factor. No inter-individual variability was
      observed within each age group. LIMITATIONS, REASONS FOR CAUTION: As our present
      study is descriptive and performed exclusively in the mouse, future functional
      studies will be required to unravel the contribution of these organelles in the
      control of reproductive functions. WIDER IMPLICATIONS OF THE FINDINGS:
      Acknowledging the important roles played by PC sensory organelles in organ
      homeostasis and development in humans, our work opens new avenues of research
      concerning the cellular control of epididymal functions, which are essential to
      male fertility. STUDY FUNDING/COMPETING INTEREST(S): Study funded by an NSERC
      operating grant to CB (RGPIN-2015-109194). No competing interest to declare.

PMID- 30239721
TI  - GLS hyperactivity causes glutamate excess, infantile cataract and profound
      developmental delay.
AB  - Loss-of-function mutations in glutaminase (GLS), the enzyme converting glutamine
      into glutamate, and the counteracting enzyme glutamine synthetase (GS) cause
      disturbed glutamate homeostasis and severe neonatal encephalopathy. We report a
      de novo Ser482Cys gain-of-function variant in GLS encoding glutaminase associated
      with profound developmental delay and infantile cataract. Functional analysis
      demonstrated that this variant causes hyperactivity and compensatory
      downregulation of GLS expression combined with upregulation of the counteracting
      enzyme GS, supporting pathogenicity. Ser482Cys-GLS likely improves the
      electrostatic environment of the GLS catalytic site, thereby intrinsically
      inducing hyperactivity. Alignment of +/-12.000 GLS protein sequences from >1000
      genera, revealed extreme conservation of Ser482, to the same degree as catalytic
      residues. Together with the hyperactivity, this indicates that Ser482 is
      evolutionarily preserved to achieve optimal -but submaximal- GLS activity. In
      line with GLS hyperactivity, increased glutamate and decreased glutamine
      concentrations were measured in urine and fibroblasts. In the brain (both grey
      and white matter), glutamate was also extremely high and glutamine almost
      undetectable, using ultra-high field magnetic resonance spectroscopic imaging.
      Considering the neurotoxicity of glutamate when present in excess, the strikingly
      high glutamate concentrations measured in the brain provide an explanation for
      the developmental delay. Cataract, a known consequence of oxidative stress, was
      evoked in zebrafish expressing the hypermorphic Ser482Cys-GLS and could be
      alleviated by inhibition of GLS. The capacity to detoxify reactive oxygen species
      was reduced upon Ser482Cys-GLS expression, providing an explanation for cataract
      formation. In conclusion, we describe an inborn error of glutamate metabolism
      caused by a GLS hyperactivity variant, illustrating the importance of balanced
      GLS activity.

PMID- 30239722
TI  - Meta-analysis of genome-wide association studies for body fat distribution in
      694,649 individuals of European ancestry.
AB  - One in four adults worldwide are either overweight or obese. Epidemiological
      studies indicate that the location and distribution of excess fat, rather than
      general adiposity, is most informative for predicting risk of obesity sequellae,
      including cardiometabolic disease and cancer. We performed a genome-wide
      association study meta-analysis of body fat distribution, measured by waist-to
      hip ratio adjusted for BMI (WHRadjBMI), and identified 463 signals in 346 loci.
      Heritability and variant effects were generally stronger in women than men, and
      we found approximately one-third of all signals to be sexually dimorphic. The 5%
      of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times
      more likely than the bottom 5% to have a WHR above the thresholds used for
      metabolic syndrome. These data, made publicly available, will inform the biology
      of body fat distribution and its relationship with disease.

PMID- 30239724
TI  - The long non-coding RNA NEAT1 is elevated in polyglutamine repeat expansion
      diseases and protects from disease gene-dependent toxicities.
AB  - Polyglutamine (polyQ) repeat diseases are a class of neurodegenerative disorders
      caused by CAG-repeat expansion. There are diverse cellular mechanisms behind the
      pathogenesis of polyQ disorders, including transcriptional dysregulation.
      Interestingly, we find that levels of the long isoform of nuclear paraspeckle
      assembly transcript 1 (Neat1L) are elevated in the brains of mouse models of
      spinocerebellar ataxia types 1, 2, 7 and Huntington's disease (HD). Neat1L was
      also elevated in differentiated striatal neurons derived from HD knock-in mice
      and in HD patient brains. The elevation was mutant Huntingtin (mHTT) dependent,
      as knockdown of mHTT in vitro and in vivo restored Neat1L to normal levels. In
      additional studies, we found that Neat1L is repressed by methyl CpG binding
      protein 2 (MeCP2) by RNA-protein interaction but not by occupancy of MeCP2 at its
      promoter. We also found that NEAT1L overexpression protects from mHTT-induced
      cytotoxicity, while reducing it enhanced mHTT-dependent toxicity. Gene set
      enrichment analysis of previously published RNA sequencing data from mouse
      embryonic fibroblasts and cells derived from HD patients shows that loss of
      NEAT1L impairs multiple cellular functions, including pathways involved in cell
      proliferation and development. Intriguingly, the genes dysregulated in HD human
      brain samples overlap with pathways affected by a reduction in NEAT1, confirming
      the correlation of NEAT1L and HD-induced perturbations. Cumulatively, the role of
      NEAT1L in polyQ disease model systems and human tissues suggests that it may play
      a protective role in CAG-repeat expansion diseases.

PMID- 30239725
TI  - Prediction of slaughter age in pigs and assessment of the predictive value of
      phenotypic and genetic information using random forest.
AB  - The weight of a pig and the rate of its growth are key elements in pig
      production. In particular, predicting future growth is extremely useful, since it
      can help in determining feed costs, pen space requirements, and the age at which
      a pig reaches a desired slaughter weight. However, making these predictions is
      challenging, due to the natural variation in how individual pigs grow, and the
      different causes of this variation. In this paper, we used machine learning,
      namely random forest (RF) regression, for predicting the age at which the
      slaughter weight of 120 kg is reached. Additionally, we used the variable
      importance score from RF to quantify the importance of different types of input
      data for that prediction. Data of 32,979 purebred Large White pigs were provided
      by Topigs Norsvin, consisting of phenotypic data, estimated breeding values
      (EBVs), along with pedigree and pedigree-genetic relationships. Moreover, we
      presented a 2-step data reduction procedure, based on random projections (RPs)
      and principal component analysis (PCA), to extract features from the pedigree and
      genetic similarity matrices for use as inputs in the prediction models. Our
      results showed that relevant phenotypic features were the most effective in
      predicting the output (age at 120 kg), explaining approximately 62% of its
      variance (i.e., R2 = 0.62). Estimated breeding value, pedigree, or pedigree
      genetic features interchangeably explain 2% of additional variance when added to
      the phenotypic features, while explaining, respectively, 38%, 39%, and 34% of the
      variance when used separately.

PMID- 30239726
TI  - Impact of Assisted Reproduction, Infertility, Sex, and Paternal Factors on the
      Placental DNA Methylome.
AB  - Children conceived using Assisted Reproductive Technologies (ART) have a higher
      incidence of growth and birth defects, attributable in part to epigenetic
      perturbations. Both ART and germline defects associated with parental infertility
      could interfere with epigenetic reprogramming events in germ cells or early
      embryos. Mouse models indicate that the placenta is more susceptible to the
      induction of epigenetic abnormalities than the embryo, and thus the placental
      methylome may provide a sensitive indicator of 'at risk' conceptuses. Our goal
      was to use genome-wide profiling to examine the extent of epigenetic
      abnormalities in matched placentas from an ART/infertility group and control
      singleton pregnancies (n=44/group) from a human prospective longitudinal birth
      cohort, the 3D Study. Principal component analysis revealed a group of ART
      outliers. The ART outlier group was enriched for females and a subset of
      placentas showing loss of methylation of several imprinted genes including GNAS,
      SGCE, KCNQT1OT1 and BLCAP/NNAT. Within the ART group, placentas from pregnancies
      conceived with IVF/ICSI showed distinct epigenetic profiles as compared to those
      conceived with less invasive procedures (ovulation induction, intrauterine
      insemination). Male factor infertility and paternal age further differentiated
      the IVF/ICSI group, suggesting an interaction of infertility and techniques in
      perturbing the placental epigenome. Together, the results suggest that the human
      placenta is sensitive to the induction of epigenetic defects by ART and/or
      infertility, and we stress the importance of considering both sex and paternal
      factors and that some but not all ART conceptuses will be susceptible.

PMID- 30239728
TI  - Antibiotic consumption in Germany: first data of a newly implemented web-based
      tool for local and national surveillance.
AB  - Objectives: The features of a newly established, web-based surveillance system
      for hospital antibiotic consumption are described and data on broad-spectrum
      antibiotic use in German acute care hospitals are presented. Methods: The watch-
      and reserve-group antibiotics, two categories of antibiotics derived from the WHO
      Essential Medicines List comprising key agents for antimicrobial stewardship,
      were used as a framework for data analysis. The median antibiotic consumption
      densities (ACDs; DDD/100 patient days) for the years 2015/16 based on data from
      137 acute care hospitals have been calculated for whole facilities, ICUs and
      medical and surgical departments, stratified by type of care. Results: The new
      web-based system provides real-time surveillance at unit and facility levels,
      accessible to all relevant stakeholders. User-defined reports are available via
      an interactive database, various report types support different approaches to
      analysis, and different complementing quantification measures of antimicrobial
      consumption are available. Watch- and reserve-group antibiotics accounted for 42%
      and 2% of total antibiotic use, respectively. Surgical services presented with
      considerably lower median ACDs of the watch-group antibiotics compared with
      medical services. Tertiary care hospitals exhibited higher ACDs of the reserve
      group antibiotics and carbapenems than primary/secondary care hospitals, while
      the ACDs of the watch-group antibiotics as a whole did not differ significantly.
      Comparing the proportional use with other European countries revealed a
      relatively high use of the watch-group, ranking beyond the 75th percentile.
      Conclusions: Because of its particular features the new web-based surveillance
      system is a valuable tool for antimicrobial stewardship. The WHO categories of
      watch- and reserve-group antibiotics proved to be a useful framework for the
      analysis of hospital antibiotic consumption data.

PMID- 30239727
TI  - Evolutionary Genomics of Metchnikovella incurvata (Metchnikovellidae): An Early
      Branching Microsporidium.
AB  - Metchnikovellids are highly specialized hyperparasites, which infect and
      reproduce inside gregarines (Apicomplexa) inhabiting marine invertebrates. Their
      phylogenetic affiliation was under constant discussion until recently, when
      analysis of the first near-complete metchnikovellid genome, that of Amphiamblys
      sp., placed it in a basal position with respect to most Microsporidia.
      Microsporidia are a highly diversified lineage of extremely reduced parasites
      related to Rozellida (Rozellosporidia = Rozellomycota = Cryptomycota) within the
      Holomycota clade of Opisthokonta. By sequencing DNA from a single-isolated
      infected gregarine cell we obtained an almost complete genome of a second
      metchnikovellid species, and the first one of a taxonomically described and well
      documented species, Metchnikovella incurvata. Our phylogenomic analyses show
      that, despite being considerably divergent from each other, M. incurvata forms a
      monophyletic group with Amphiamplys sp., and confirm that metchnikovellids are
      one of the deep branches of Microsporidia. Comparative genomic analysis
      demonstrates that, like most Microsporidia, metchnikovellids lack mitochondrial
      genes involved in energy transduction and are thus incapable of synthesizing
      their own ATP via mitochondrial oxidative phosphorylation. They also lack the
      horizontally acquired ATP transporters widespread in most Microsporidia. We
      hypothesize that a family of mitochondrial carrier proteins evolved to transport
      ATP from the host into the metchnikovellid cell. We observe the progressive
      reduction of genes involved in DNA repair pathways along the evolutionary path of
      Microsporidia, which might explain, at least partly, the extremely high
      evolutionary rate of the most derived species. Our data also suggest that genome
      reduction and acquisition of novel genes co-occurred during the adaptation of
      Microsporidia to their hosts.

PMID- 30239730
TI  - Fecal indicator bacteria and zoonotic pathogens in marine snow and California
      mussels (Mytilus californianus).
AB  - Pollution of nearshore waters with disease-causing microorganisms impacts
      ecosystems health through illness and deaths in people and wildlife, as well as
      negative socioeconomic consequences of impaired marine resources. Insight on
      pathogen ecology in coastal habitats is crucial for accurately mitigating inputs
      and impacts of microbial pollution. Three objectives were addressed to (i)
      compare fecal pollution in proximity to (a) freshwater runoff, and (b) endemic
      marine wildlife; (ii) evaluate presence and magnitude of fecal microorganisms in
      marine snow and mussels and (iii) determine if pathogens in mussels and FIB
      levels in seawater or mussels are correlated. Sampling during the wet season,
      proximity to freshwater, and FIB levels in mussel homogenates (but not seawater)
      were associated with pathogen presence in mussels. Pathogens and FIB were
      enriched in aggregate-rich fractions, further supporting an important role of
      marine snow in pathogen transmission. The lack of association between FIB in
      surrounding waters and presence of pathogens in mussels calls into question
      current regulations for insuring safe seafood to consumers in the United States,
      and alternative monitoring approaches such as direct testing for select pathogens
      should be further evaluated.

PMID- 30239731
TI  - Editorial: Deep life, kia ora!

PMID- 30239729
TI  - The Grayling Genome Reveals Selection on Gene Expression Regulation after Whole
      Genome Duplication.
AB  - Whole-genome duplication (WGD) has been a major evolutionary driver of increased
      genomic complexity in vertebrates. One such event occurred in the salmonid family
      ~80 Ma (Ss4R) giving rise to a plethora of structural and regulatory duplicate
      driven divergence, making salmonids an exemplary system to investigate the
      evolutionary consequences of WGD. Here, we present a draft genome assembly of
      European grayling (Thymallus thymallus) and use this in a comparative framework
      to study evolution of gene regulation following WGD. Among the Ss4R duplicates
      identified in European grayling and Atlantic salmon (Salmo salar), one-third
      reflect nonneutral tissue expression evolution, with strong purifying selection,
      maintained over ~50 Myr. Of these, the majority reflect conserved tissue
      regulation under strong selective constraints related to brain and neural-related
      functions, as well as higher-order protein-protein interactions. A small subset
      of the duplicates have evolved tissue regulatory expression divergence in a
      common ancestor, which have been subsequently conserved in both lineages,
      suggestive of adaptive divergence following WGD. These candidates for adaptive
      tissue expression divergence have elevated rates of protein coding- and promoter
      sequence evolution and are enriched for immune- and lipid metabolism ontology
      terms. Lastly, lineage-specific duplicate divergence points toward underlying
      differences in adaptive pressures on expression regulation in the nonanadromous
      grayling versus the anadromous Atlantic salmon. Our findings enhance our
      understanding of the role of WGD in genome evolution and highlight cases of
      regulatory divergence of Ss4R duplicates, possibly related to a niche shift in
      early salmonid evolution.

PMID- 30239734
TI  - Validation and calibration of self-reported height and weight in the Danish
      Health Examination Survey.
AB  - Background: Body mass index (BMI) derived from self-reported information is
      widely used and the validity is therefore crucial. We aim at testing the validity
      of self-reported height and weight, and to test if the accuracy of self-reported
      information can be improved by calibration by testing if calibration improved the
      ability to predict diabetes. Methods: Data from Danish Health Examination Survey
      (DANHES) was used. 15 692 participants who had both filled out questionnaire and
      participated in health examination, and 54 725 participants with questionnaire
      alone, were included. Data was analyzed using Pearson's R, Cohens Kappa, linear
      regression and Cox-regression. Self-reported values of height and weight were
      calibrated using coefficients obtained from linear regression analysis. To
      evaluate if the calibration improved the ability to predict diabetes, Akaike's
      information criterion was used. Results: Self-reported height, weight and BMI
      were highly correlated with measured values (R >= 0.92). BMI was under-reported
      by 0.32 kg m-2 and 0.38 kg m-2 in women and men. The hazard ratio (HR) (95%
      confidence interval) for diabetes according to measured BMI was 2.09 (1.89-2.27)
      and for self-reported BMI was 1.60 (1.50-1.70) per 5 kg m-2. Calibrated values of
      self-reported BMI improved the predictive value of BMI for the risk of diabetes.
      Conclusions: Self-reported height and weight correlated highly with physical
      measurement of height and weight. Measured values of BMI were more strongly
      associated with diabetes risk as compared to self-reported values. Calibration of
      the self-reported values improved the accuracy of self-reported height and
      weight.

PMID- 30239732
TI  - Endometriosis and adverse maternal, fetal and neonatal outcomes, a systematic
      review and meta-analysis.
AB  - STUDY QUESTION: How is endometriosis associated with adverse maternal, fetal and
      neonatal outcomes of pregnancy? SUMMARY ANSWER: Women with endometriosis are at
      elevated risk for serious and important adverse maternal (pre-eclampsia,
      gestational diabetes, placenta praevia and Cesarean section) and fetal or
      neonatal outcomes (preterm birth, PPROM, small for gestational age, stillbirth
      and neonatal death). WHAT IS KNOWN ALREADY: A number of studies have shown an
      association between endometriosis and certain adverse maternal and fetal
      outcomes, but the results have been conflicting with potential for confounding by
      the use of assisted reproductive technology. STUDY DESIGN, SIZE, DURATION: A
      systematic review and meta-analysis of observational studies (1 January 1990-31
      December 2017) that evaluated the effect of endometriosis on maternal, fetal and
      neonatal outcomes was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Studies were considered for inclusion if they were prospective or retrospective
      cohort or case-control studies; included women greater than 20 weeks gestational
      age with endometriosis; included a control group of gravid women without
      endometriosis; and, reported at least one of the outcomes of interest. Each study
      was reviewed for inclusion, data were extracted and risk of bias was assessed by
      two independent reviewers. MAIN RESULTS AND THE ROLE OF CHANCE: The search
      strategy identified 33 studies (sample size, n = 3 280 488) for inclusion.
      Compared with women without endometriosis, women with endometriosis had higher
      odds of pre-eclampsia (odds ratio [OR] = 1.18 [1.01-1.39]), gestational
      hypertension and/or pre-eclampsia (OR = 1.21 [1.05-1.39]), gestational diabetes
      (OR = 1.26 [1.03-1.55]), gestational cholestasis (OR = 4.87 [1.85-12.83]),
      placenta praevia (OR = 3.31 [2.37, 4.63]), antepartum hemorrhage (OR = 1.69 [1.38
      2.07]), antepartum hospital admissions (OR = 3.18 [2.60-3.87]), malpresentation
      (OR = 1.71 [1.34, 2.18]), labor dystocia (OR = 1.45 [1.04-2.01]) and cesarean
      section (OR = 1.86 [1.51-2.29]). Fetuses and neonates of women with endometriosis
      were also more likely to have preterm premature rupture of membranes (OR = 2.33
      [1.39-3.90]), preterm birth (OR = 1.70 [1.40-2.06]), small for gestational age
      <10th% (OR = 1.28 [1.11-1.49]), NICU admission (OR = 1.39 [1.08-1.78]),
      stillbirth (OR = 1.29 [1.10, 1.52]) and neonatal death (MOR = 1.78 [1.46-2.16]).
      Among the subgroup of women who conceived spontaneously, endometriosis was found
      to be associated with placenta praevia, cesarean section, preterm birth and low
      birth weight. Among the subgroup of women who conceived with the use of assisted
      reproductive technology, endometriosis was found to be associated with placenta
      praevia and preterm birth. LIMITATIONS, REASONS FOR CAUTION: As with any
      systematic review, the review is limited by the quality of the included studies.
      The diagnosis for endometriosis and the selection of comparison groups were not
      uniform across studies. However, the effect of potential misclassification would
      be bias towards the null hypothesis. WIDER IMPLICATIONS OF THE FINDINGS: The
      association between endometriosis with the important and serious pregnancy
      outcomes observed in our meta-analysis, in particular stillbirth and neonatal
      death, is concerning and warrants further studies to elucidate the mechanisms for
      the observed findings. STUDY FUNDING/COMPETING INTEREST(S): Dr Shifana Lalani is
      supported by a Physicians' Services Incorporated Foundation Research Grant, and
      Dr Innie Chen is supported by a University of Ottawa Clinical Research Chair in
      Reproductive Population Health and Health Services. Dr Singh declares conflicts
      of interests with Bayer, Abvie, Allergan and Cooper Surgical. All other authors
      have no conflicts of interests to declare. REGISTRATION NUMBER: PROSPERO
      CRD42015013911.

PMID- 30239733
TI  - Patient and healthcare provider views on a patient-reported outcomes portal.
AB  - Background: Over the past decade, public interest in managing health-related
      information for personal understanding and self-improvement has rapidly expanded.
      This study explored aspects of how patient-provided health information could be
      obtained through an electronic portal and presented to inform and engage patients
      while also providing information for healthcare providers. Methods: We invited
      participants using ResearchMatch from 2 cohorts: (1) self-reported healthy
      volunteers (no medical conditions) and (2) individuals with a self-reported
      diagnosis of anxiety and/or depression. Participants used a secure web
      application (dashboard) to complete the PROMIS(r) domain survey(s) and then
      complete a feedback survey. A community engagement studio with 5 healthcare
      providers assessed perspectives on the feasibility and features of a portal to
      collect and display patient provided health information. We used bivariate
      analyses and regression analyses to determine differences between cohorts.
      Results: A total of 480 participants completed the study (239 healthy, 241
      anxiety and/or depression). While participants from the tw2o cohorts had
      significantly different PROMIS scores (p < .05), both cohorts welcomed the
      concept of a patient-centric dashboard, saw value in sharing results with their
      healthcare provider, and wanted to view results over time. However, factors
      needing consideration before widespread use included personalization for the
      patient and their health issues, integration with existing information (eg
      electronic health records), and integration into clinician workflow. Conclusions:
      Our findings demonstrated a strong desire among healthy people, patients with
      chronic diseases, and healthcare providers for a self-assessment portal that can
      collect patient-reported outcome metrics and deliver personalized feedback.

PMID- 30239735
TI  - Aggregation makes a protein allergenic at the challenge phase of basophil
      mediated allergy in mice.
AB  - Hapten is a small molecule that is not immunogenic on its own but can stimulate
      the production of antibodies at the sensitization phase when conjugated to
      carrier proteins. The hapten then reacts specifically with the antibodies
      generated against it to elicit an immune or allergic response at the challenge
      phase. Here we compared various carrier proteins conjugated with the same hapten
      in their ability to induce hapten-specific IgE-mediated allergic responses in
      vitro and in vivo, and characterized the nature of carrier proteins that
      determines the magnitude of response at the challenge phase of allergic
      reactions. Hapten TNP-conjugated ovalbumin (TNP-OVA) and bovine serum albumin
      (TNP-BSA) elicited TNP-specific, mast cell-dependent, immediate-type allergic
      reactions at a comparable level in mice that had been passively sensitized with
      TNP-specific IgE. In contrast, TNP-OVA but not TNP-BSA efficiently induced a
      basophil-dependent, IgE-mediated chronic allergic inflammation (IgE-CAI), even
      though both proteins could stimulate basophils in vitro at a comparable level. By
      comparing different carrier proteins and structurally modifying them, we found
      that the formation of large aggregates is crucial for TNP-conjugated carrier
      proteins to efficiently elicit IgE-CAI, regardless of the type of proteins. Thus,
      aggregation status of carrier proteins appears to determine the magnitude of
      allergic response at the challenge phase of hapten-specific IgE-CAI. Our findings
      suggest that the allergenicity of substances is a matter of importance not only
      at the sensitization but also at the challenge phase in a certain type of allergy
      including a basophil-mediated allergic inflammation.

PMID- 30239736
TI  - Suppression of myopathic lamin mutations by muscle-specific activation of AMPK
      and modulation of downstream signaling.
AB  - Laminopathies are diseases caused by dominant mutations in the human LMNA gene
      encoding A-type lamins. Lamins are intermediate filaments that line the inner
      nuclear membrane, provide structural support for the nucleus, and regulate gene
      expression. Drosophila melanogaster models of skeletal muscle laminopathies were
      developed to investigate the pathological defects caused by mutant lamins and
      identify potential therapeutic targets. Human disease-causing LMNA mutations were
      modeled in Drosophila Lamin C (LamC) and expressed in indirect flight muscle
      (IFM). IFM-specific expression of mutant, but not wild-type LamC, caused held-up
      wings indicative of myofibrillar defects. Analyses of the muscles revealed
      cytoplasmic aggregates of nuclear envelope (NE) proteins, nuclear and
      mitochondrial dysmorphology, myofibrillar disorganization, and up-regulation of
      the autophagy cargo receptor p62. We hypothesized that the cytoplasmic aggregates
      of NE proteins trigger signaling pathways that alter cellular homeostasis,
      causing muscle dysfunction. In support of this hypothesis, transcriptomics data
      from human muscle biopsy tissue revealed misregulation of the AMPK/4E
      BP1/autophagy/proteostatic pathways. S6K mRNA levels were increased and AMPKalpha
      and mRNAs encoding downstream targets were decreased in muscles expressing mutant
      LMNA relative controls. The Drosophila laminopathy models were used to determine
      if altering the levels of these factors modulated muscle pathology. Muscle
      specific over-expression of AMPKalpha and down-stream targets 4E-BP, Foxo and
      PGC1alpha, as well as inhibition of S6K, suppressed the held-up wing phenotype,
      myofibrillar defects, and LamC aggregation. These findings provide novel insights
      on mutant LMNA-based disease mechanisms and identify potential targets for drug
      therapy.

PMID- 30239737
TI  - Burn Patients' Perceptions of Their Care: What can we learn from post-discharge
      satisfaction surveys?
AB  - Introduction: Little is understood about the inpatient experience from the burn
      patients' perspectives. Rather, hospitals emphasize quantitative feedback as part
      of the ongoing process improvement. Comments returned with the Hospital Consumer
      Assessment of Healthcare Providers and Systems (HCAHPS) administrative survey may
      provide important patient perspectives. We analyzed quantitative and qualitative
      HCAHPS data to identify areas for care improvement. Methods: We reviewed our burn
      center HCAHPS results over 2 years. We analyzed "top-box" result in each defined
      HCAHPS category, which is the most frequently reported best result in each
      composite, including survey scores 3 9 (out of 10). We performed qualitative
      content analysis of open-text responses via a HIPAA-compliant analysis software.
      We developed a hierarchy of major expressed themes, and organized them using
      HCAHPS-validated satisfaction domains. Results: A total of 610 inpatient HCAHPS
      surveys (21% response rate) were returned. Seventy-five percent of respondents
      ranked our burn center as a 3 9 (out of 10) in care scores. Content analysis
      identified 3 main components of the inpatient experience: 1) provider/nurse
      communication, 2) hospital environment, and 3) the discharge experience. Caring,
      respect, handoff coordination, explanations, listening, and confidence in
      provider constituted the six key communication themes. Patients generally
      reported that burn providers listened to their concerns, but others requested
      clearer explanations of their condition and care. Responses about hospital
      environment highlighted excessive noise and disrupted sleep, and variable
      responses related to cleanliness. Challenges in the discharge experience included
      difficulties procuring wound care supplies and discharge medications.
      Conclusions: Qualitative data from HCAHPS helped identify major target areas for
      burn center performance improvement. Analysis of HCAHPS direct patient feedback
      is useful in process improvement, whereas numerical data alone do not provide
      sufficient actionable information.

PMID- 30239738
TI  - The impact of a thin endometrial lining on fresh and frozen-thaw IVF outcomes: an
      analysis of over 40 000 embryo transfers.
AB  - STUDY QUESTION: Does each millimeter decrease in endometrial thickness lead to
      lower pregnancy and live birth rates in fresh and frozen IVF cycles? SUMMARY
      ANSWER: Clinical pregnancy and live birth rates decline as the endometrial
      thickness decreases below 8 mm in fresh IVF-ET and below 7 mm in frozen-thaw
      embryo transfer (ET) cycles. WHAT IS KNOWN ALREADY: Previous studies have been
      heterogenous and have shown conflicting results on the impact of endometrial
      thickness on IVF outcomes. Most studies do not include many patients with an
      endometrial thickness below 6 mm, and there are few studies of frozen-thaw ET
      cycles. STUDY DESIGN, SIZE, DURATION: This study is a retrospective cohort
      analysis of all Canadian IVF fresh and frozen-thaw ET cycles from the CARTR-BORN
      database for autologous and donor fresh and frozen-thaw IVF-ET cycles from 1
      January 2013 to 31 December 2015. A total of 24 363 fresh and 20 114 frozen-thaw
      IVF-ET cycles were reported during this timeframe. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: 33 Canadians clinics participated in voluntary reporting of IVF
      and pregnancy outcomes to the CARTR-BORN database. The impact of endometrial
      thickness on pregnancy, live birth and pregnancy loss rates were analyzed for
      fresh IVF-ET and frozen-thaw cycles. MAIN RESULTS AND THE ROLE OF CHANCE: In
      fresh IVF-ET cycles, clinical pregnancy and live birth rates decreased (P <
      0.0001) and pregnancy loss rates increased (P = 0.01) with each millimeter
      decline in endometrial thickness below 8 mm. Live birth rates were 33.7, 25.5,
      24.6 and 18.1% for endometrial thickness >=8, 7-7.9, 6-6.9 and 5-5.9 mm,
      respectively. In frozen-thaw ET cycles, clinical pregnancy (P = 0.007) and live
      birth rates decreased (P = 0.002) with each millimeter decline in endometrial
      thickness below 7 mm, with no significant difference in pregnancy loss rates.
      Live birth rates were 28.4, 27.4, 23.7, 15 and 21.2% for endometrial thickness
      >=8, 7-7.9, 6-6.9, 5-5.9 and 4-4.9 mm, respectively. The likelihood of achieving
      an endometrial thickness >=8 mm decreased with age (89.7, 87.8 and 83.9% in women
      <35, 35-39 and >=40, respectively) (P < 0.0001). LIMITATIONS, REASONS FOR
      CAUTION: This study only included cycles which proceeded to ET, which may
      overestimate pregnancy outcomes. Approximately 8% of cycles could not be included
      in the analysis due to data irregularity related to data entry. Demographic data
      aside from age were unavailable but may be important as lower endometrial
      thickness may be associated with poor ovarian response. WIDER IMPLICATIONS OF THE
      FINDINGS: Although pregnancy and live birth rates decrease with endometrial
      thickness, reasonable outcomes were obtained even with lower endometrial
      thickness measurements. These data provide valuable guidance for both physicians
      and patients when confronted with decisions related to a persistently thin
      endometrium. STUDY FUNDING/COMPETING INTEREST(S): This study was not funded. The
      authors do not have any conflicts of interests to declare. TRIAL REGISTRATION
      NUMBER: N/A.

PMID- 30239739
TI  - Long-term consumption of fruits and vegetables and risk of chronic obstructive
      pulmonary disease: a prospective cohort study of women.
AB  - Background: Fruits and vegetables, due to high antioxidant capacity, may protect
      the lung from oxidative damage caused by tobacco smoke and potentially prevent
      chronic obstructive pulmonary disease (COPD). Only one study based on baseline
      diet has examined fruit and vegetable consumption in relation to risk of COPD,
      and no previous studies have examined long-term diet. Methods: We investigated
      whether long-term fruit and vegetable consumption was associated with COPD
      incidence among 34 739 women (age 48-83 years) in the population-based
      prospective Swedish Mammography Cohort. Fruit and vegetable consumption was
      assessed twice (1987, 1997) with a self-administered questionnaire. Cases of COPD
      were identified by linkage to the Swedish health register. Cox proportional
      hazard regression models were used to estimate hazard ratios (HRs) and 95%
      confidence intervals (CIs). Results: During follow-up from 2002 to 2014, 1512
      women were diagnosed with COPD. Long-term fruit was associated with lower risk of
      COPD; women in the highest vs lowest quintile of consumption (>=2.5 vs <0.8
      servings/day) had a 37% lower risk of COPD (95% CI: 25-48%; P-trend < 0.0001). No
      association was observed with long-term vegetable intake. Current and ex-smokers
      with low long-term consumption of fruits (<1 serving/day) in comparison to never
      smokers with high consumption (>=3 servings/day) had a 38-fold (HR: 38.1; 95% CI:
      20.2-71.7) and 13-fold (HR: 12.5, 95% CI: 6.5-24.1) higher risk of COPD,
      respectively. However, no significant interaction between smoking status and
      fruit intake in relation to COPD incidence was observed (P-interaction = 0.95).
      Conclusions: In this prospective cohort of middle-age and older women, long-term
      consumption of fruits but not vegetables was inversely associated with COPD
      incidence.

PMID- 30239740
TI  - Keep it in the family: comparing perinatal risks in small-for-gestational-age
      infants based on population vs within-sibling designs.
AB  - Background: Small-for-gestational-age (SGA) birth is commonly used as a proxy for
      fetal growth restriction, but also includes constitutionally small infants.
      Genetic factors account for almost half of the risk of SGA birth. We estimated
      perinatal risks of SGA birth using both population-based and within-sibling
      analyses, where the latter by design controls for shared genetic factors and
      maternal environmental factors that are constant across pregnancies. Methods:
      This was a prospective nationwide cohort study of 2 616 974 singleton infants
      born in Sweden between January 1987 and December 2012, of whom 1 885 924 were
      full siblings. We estimated associations between severe or moderate SGA (<3rd
      percentile and 3rd to <10th percentiles, respectively) and risks of stillbirth,
      neonatal mortality and morbidity, using both population-based and within-sibling
      analyses. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated
      in stillbirth analyses, whereas relative risks (RRs) were used for analyses of
      neonatal outcomes. Results: Compared with non-SGA births (>10th percentile), the
      HR (95% CI) of stillbirth was 18.5 (95% CI 17.4-19.5) among severe SGA births in
      the population analysis and 22.5 (95% CI 18.7-27.1) in the within-sibling
      analysis. In non-malformed infants, RRs for neonatal mortality in moderate and
      severe SGA infants were similarly increased in both population and within-sibling
      analyses. In term non-malformed infants (>=37 weeks), SGA-related RRs of several
      neonatal morbidities were higher in within-sibling than in population analyses.
      Conclusions: Perinatal risks associated with fetal growth restriction are more
      accurately estimated from analyses of SGA in which genetic factors are accounted
      for.

PMID- 30239741
TI  - Innovative training networks: overview of the Marie Sklodowska-Curie PhD training
      model.
AB  - Doctoral training has changed in recent years with most PhDs now performed in
      structured programmes operated by university graduate schools. These schools
      generally superimpose a training framework onto the traditional research project
      to improve the education experience of the students and to prepare them for their
      careers. Many graduates progress to the commercial sector, where there is demand
      for highly skilled employees. The European Union (EU) promotes the development of
      transnational, training-focused, PhD programmes called Innovative Training
      Networks (ITNs) through Marie Sklodowska-Curie Actions. ITNs share many features
      of thematic PhD programmes, but they only recruit a single cohort of students,
      and they align with EU policy goals. These training networks are prestigious and
      very well regarded within European academia. The authors of this article were
      participants in a yeast biotechnology ITN, YEASTCELL, which finished in 2017.
      Some interesting insights into the more and less successful aspects of the
      project arose during discussions at the final project workshop. The views of the
      participants are distilled here in a discussion of how an ITN could be structured
      to maximise the benefits for the three main stakeholders: students, supervisors
      and industry partners.

PMID- 30239742
TI  - Preconception and prenatal cannabis use and the risk of behavioural and emotional
      problems in the offspring; a multi-informant prospective longitudinal study.
AB  - Background: Studies of the long-term consequences of maternal cannabis use on
      child development beyond the neonatal period are sparse. In the current study, we
      use a multi-information approach to assess the association of prenatal cannabis
      exposure and child behavioural and emotional functioning. To explore the possible
      causal nature of the association, we investigated whether maternal tobacco and
      paternal cannabis use during pregnancy were also associated with child problems.
      Methods: The study population included children of a population-based birth
      cohort in The Netherlands (n = 5903). Information on parental cannabis use was
      collected using questionnaires; urine of mothers was analysed for the presence of
      cannabis metabolites. Child behavioural and emotional problems at approximately 7
      10 years were measured using validated teacher-, child- and mother-reports.
      Results: Our findings show associations of maternal cannabis use during pregnancy
      with offspring externalising problems (B = 0.53; 95% CI: 0.29-0.77), but not with
      internalising problems (B = -0.10; 95% CI: -0.31-0.11). However, maternal
      cannabis use before pregnancy was also associated with offspring externalising
      problems (B = 0.27; 95% CI: 0.02-0.52). Further, cannabis use by the father was
      associated with child externalising problems (B = 0.36; 95% CI: 0.22-0.49) but
      not internalising problems. Conclusions: Prenatal exposure to maternal cannabis
      use is specifically associated with offspring behavioural problems, but not
      emotional problems. This association is probably not due to an effect of
      intrauterine cannabis exposure on fetal development, because both maternal and
      paternal cannabis exposure during pregnancy were related to offspring
      externalising problems. Our findings suggest that the association can be
      explained through residual confounding, most likely through shared genetic
      vulnerabilities for parental cannabis use and offspring behavioural problems.

PMID- 30239743
TI  - Effect of aminoacyl-tRNA synthetase mutations on susceptibility to ciprofloxacin
      in Escherichia coli.
AB  - Background: Chromosomal mutations that reduce ciprofloxacin susceptibility in
      Escherichia coli characteristically map to drug target genes (gyrAB and parCE),
      and genes encoding regulators of the AcrAB-TolC efflux pump. Mutations in RNA
      polymerase can also reduce susceptibility, by up-regulating the MdtK efflux pump.
      Objectives: We asked whether mutations in additional chromosomal gene classes
      could reduce susceptibility to ciprofloxacin. Methods: Experimental evolution,
      complemented by WGS analysis, was used to select and identify mutations that
      reduce susceptibility to ciprofloxacin. Transcriptome analysis, genetic
      reconstructions, susceptibility measurements and competition assays were used to
      identify significant genes and explore the mechanism of resistance. Results:
      Mutations in three different aminoacyl-tRNA synthetase genes (leuS, aspS and
      thrS) were shown to reduce susceptibility to ciprofloxacin. For two of the genes
      (leuS and aspS) the mechanism was partially dependent on RelA activity. Two
      independently selected mutations in leuS (Asp162Asn and Ser496Pro) were studied
      in most detail, revealing that they induce transcriptome changes similar to a
      stringent response, including up-regulation of three efflux-associated loci
      (mdtK, acrZ and ydhIJK). Genetic analysis showed that reduced susceptibility
      depended on the activity of these loci. Broader antimicrobial susceptibility
      testing showed that the leuS mutations also reduce susceptibility to additional
      classes of antibiotics (chloramphenicol, rifampicin, mecillinam, ampicillin and
      trimethoprim). Conclusions: The identification of mutations in multiple tRNA
      synthetase genes that reduce susceptibility to ciprofloxacin and other
      antibiotics reveals the existence of a large mutational target that could
      contribute to resistance development by up-regulation of an array of efflux
      pumps.

PMID- 30239744
TI  - C-type natriuretic peptide improves growth retardation in a mouse model of cardio
      facio-cutaneous syndrome.
AB  - Cardio-facio-cutaneous (CFC) syndrome, a genetic disorder caused by germline
      mutations in BRAF, KRAS, MAP2K1 and MAP2K2, is characterized by growth
      retardation, heart defects, dysmorphic facial appearance and dermatologic
      abnormalities. We have previously reported that knock-in mice expressing the CFC
      syndrome-associated mutation, Braf Q241R, showed growth retardation because of
      gastrointestinal dysfunction. However, other factors associated with growth
      retardation, including chondrogenesis and endocrinological profile, have not been
      examined. Here, we show that 3- and 4-week-old BrafQ241R/+ mice have decreased
      body weight and length, as well as reduced growth plate width in the proximal
      tibiae. Furthermore, proliferative and hypertrophic chondrocyte zones of the
      growth plate were reduced in BrafQ241R/+ mice compared with Braf+/+ mice.
      Immunohistological analysis revealed that ERK activation was enhanced in
      hypertrophic chondrocytes in BrafQ241R/+ mice. In accordance with growth
      retardation and reduced growth plate width, decreased serum levels of insulin
      like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) were observed in
      BrafQ241R/+ mice at 3 and 4 weeks of age. Treatment with C-type natriuretic
      peptide (CNP), a stimulator of endochondral bone growth and a potent inhibitor of
      the FGFR3-RAF1-MEK/ERK signaling, increased body and tail lengths in Braf+/+ and
      BrafQ241R/+ mice. In conclusion, ERK activation in chondrocytes and low serum IGF
      1/IGFBP-3 levels could be associated with the growth retardation observed in
      BrafQ241R/+ mice. Our data also suggest that CNP is a potential therapeutic
      target in CFC syndrome.

PMID- 30239745
TI  - Mannoside Glycolipid Conjugates Display Antiviral Activity Against Ebola Virus.
AB  - The West African outbreak of Ebola virus (EBOV) infection during 2013-2016
      highlighted the need for development of field-applicable therapeutic drugs for
      this infection. Here we report that mannoside glycolipid conjugates (MGCs)
      consisting of a trimannose head and a lipophilic chain assembled by a linker
      inhibit EBOV infection not only of human monocyte-derived dendritic cells and
      macrophages, but also of a number of susceptible cells. Analysis of the mode of
      action leads us to conclude that MGCs act directly on cells, notably by
      preventing virus endocytosis.

PMID- 30239747
TI  - Endothelial Colony Forming Cell Function Is Reduced in HIV.
AB  - Background: HIV may be related to cardiovascular disease through monocyte
      activation-associated endothelial dysfunction. Methods: Blood samples from 15 HIV
      , 8 HIV+/ART-, and 15 HIV+/ART+ participants underwent flow cytometric
      measurement of endothelial colony forming cells (ECFC) and monocyte proportions.
      IncuCyte live cell imaging measurements of eight capillary proliferative capacity
      parameters were obtained from cord blood-ECFC treated with participant plasma.
      Results: ECFC% by flow cytometry was not different between the study groups;
      however, the majority of capillary proliferative capacity parameters (cell area,
      network length, network branch points, number of networks, and average tube width
      uniformity) were significantly lower in HIV+/ART- participants compared to HIV-
      controls or HIV+/ART+ participants (all P<0.00625). CD14+CD16+ intermediate
      monocytes and sCD163 were significantly and negatively correlated with several
      plasma-treated, cord blood-ECFC proliferative capacity parameters in the combined
      HIV+ groups but not in the HIV- group. Conclusions: Cord blood ECFC proliferative
      capacity was significantly impaired by plasma from HIV+/ART- patients when
      compared to HIV- and HIV+/ART+ samples. Several ECFC functional parameters were
      adversely associated with monocyte activation in the HIV+ groups, thereby
      suggesting a mechanism by which HIV-related inflammation may impair vascular
      reparative potential and consequently increase risk of cardiovascular disease in
      HIV.

PMID- 30239746
TI  - Characterization of copy number variants in a large multibreed population of beef
      and dairy cattle using high-density single nucleotide polymorphism genotype data.
AB  - Copy number variants (CNVs) are a form of genomic variation that changes the
      structure of the genome through deletion or duplication of stretches of DNA. The
      objective of the present study was to characterize CNVs in a large multibreed
      population of beef and dairy bulls. The CNVs were called on the autosomes of
      5,551 cattle from 22 different beef and dairy breeds, using 2 freely available
      software suites, QuantiSNP and PennCNV. All CNVs were classified into either
      deletions or duplications. The median concordance between PennCNV and QuantiSNP,
      per animal, was 18.5% for deletions and 0% for duplications. The low concordance
      rate between PennCNV and QuantiSNP indicated that neither algorithm, by itself,
      could identify all CNVs in the population. In total, PennCNV and QuantiSNP
      collectively identified 747,129 deletions and 432,523 duplications; 80.2% of all
      duplications and 69.1% of all deletions were present only once in the population.
      Only 0.154% of all CNVs identified were present in more than 50 animals in the
      population. The distribution of the percentage of the autosomes that were
      composed of deletions, per animal, was positively skewed, as was the distribution
      for the percentage of the autosomes that were composed of duplications, per
      animal. The first quartile, median, and third quartile of the distribution of the
      percentage of the autosomes that were composed of deletions were 0.019%, 0.037%,
      and 0.201%, respectively. The first quartile, median, and third quartile of the
      distribution of the percentage of the autosomes that were composed of
      duplications were 0.013%, 0.028%, and 0.076%, respectively. The distributions of
      the number of deletions and duplications per animal were both positively skewed.
      The interquartile range for the number of deletions per animal in the population
      was between 16 and 117, whereas for duplications it was between 8 and 23. Per
      animal, there tended to be twice as many deletions as duplications. The
      distribution of the length of deletions was positively skewed, as was the
      distribution of the length of duplications. The interquartile range for the
      length of deletions in the population was between 25 and 101 kb, and for
      duplications the interquartile range was between 46 and 235 kb. Per animal,
      duplications tended to be twice as long as deletions. This study provides a
      description of the characteristics and distribution of CNVs in a large multibreed
      population of beef and dairy cattle.

PMID- 30239748
TI  - Circuit mechanisms of reward, anhedonia and depression.
AB  - Pleasure and motivation are important factors for goal-directed behaviour and
      wellbeing in both animals and humans. Intact hedonic capacity requires an
      undisturbed interplay between a number of different brain regions and transmitter
      systems. Concordantly, dysfunction of networks encoding for reward have been
      shown in depression and other psychiatric disorders. The development of
      technological possibilities to investigate connectivity on a functional level in
      humans and to directly influence networks in animals using optogenetics among
      other techniques has provided new important insights in this field of research
      (Lenz and Lobo, 2013; Ferenczi et al., 2016).In this review we aim to provide an
      overview on the neurobiological substrates of anhedonia on a network level. For
      this purpose definition of anhedonia and the involved reward components are
      described first, then current data on reward networks in healthy individuals and
      in depressed patients are summarized and the roles of different neurotransmitter
      systems involved in reward processing are specified. Based on this information,
      the impact of different therapeutic approaches on reward processing is described
      with a particular focus on deep brain stimulation (DBS) as a possibility for a
      direct modulation of human brain structures in vivo.Overall, results of current
      studies emphasize on the importance of anhedonia in psychiatric disorders and the
      relevance of targeting this phenotype for a successful psychiatric treatment.
      However, more data incorporating these results for the refinement of
      methodological approaches are needed in order to be able to develop individually
      tailored therapeutic concepts based on both clinical and neurobiological profiles
      of patients.

PMID- 30239749
TI  - Type-specific anal human papillomavirus prevalence among men, according to sexual
      preference and HIV status: a systematic literature review and meta-analysis.
AB  - Background: Anal human papillomavirus (HPV) infection, most notably of HPV16, the
      central cause of anal cancer, is increased by anal sexual intercourse and
      worsened by HIV-positivity. Methods: We undertook a systematic review and meta
      analysis of studies reporting type-specific anal HPV infection in men, according
      to sexual preference, HIV status and, when available, anal cytopathology. HPV
      prevalence was compared by prevalence ratios (PR). Results: 79 eligible studies
      were included, comprising 23,700 men: 1,805 HIV-negative men-who-have-sex-with
      women (MSW), 924 HIV-positive MSW, 8,213 HIV-negative men-who-have-sex-with-men
      (MSM) and 12,758 HIV-positive MSM. In analyses irrespective of anal
      cytopathology, HPV16 prevalence was significantly higher in MSM than MSW, both
      among HIV-negative (14% versus 3%; PR 4.7, 95%CI 2.5-8.9) and HIV-positive men
      (30% versus 11%; PR=2.8, 95%CI 1.9-4.1). Likewise, HPV16 was significantly higher
      in HIV-positive than HIV-negative men, both among MSW (PR=3.5, 95%CI 1.6-7.7) and
      MSM (PR=2.1, 95%CI 1.8-2.5). Anal HPV16 prevalence was similar between HIV
      positive MSW and HIV-negative MSM (PR=1.3, 95% CI 0.9-2.0). For MSM, anal HPV16
      prevalence was significantly higher from studies with anal cytopathology,
      suggesting population sampling effects. Conclusion: Sexual preference and HIV
      infection are independent and similarly strong determinants of male anal HPV16
      infection, confirming HIV-positive MSM as priorities for anal cancer prevention.

PMID- 30239750
TI  - Inclusion of 'Total Worker Health(r)' a program by NIOSH.

PMID- 30239751
TI  - 1-hour and 2-hour post-load glucose level on oral glucose tolerance test and the
      risk of incident metabolic syndrome.
AB  - Background: Metabolic syndrome (MetS) increases the cardiometabolic risk even in
      non-diabetic population. Previous studies have demonstrated that 1-hour post-load
      glucose (1-hr PG) and 2-hour post-load glucose (2-hr PG) based on oral glucose
      tolerance test (OGTT) predicted cardiometabolic risk. However, it is still
      unclear whether and to what extent pos-load glucose associates with the risk of
      MetS. Methods: 5,389 non-diabetic Koreans were dichotomized into normoglycemic
      groups (NG) and abnormal glycemic groups based on OGTT including elevated 1-hr PG
      (155-199 mg/dL) and IGT (2-hr PG: 140-199 mg/dL), and followed-up for 10 years.
      Cox proportional hazard model was used to evaluate hazard ratios (HRs) with 95%
      confidence interval (CI) [adjusted HRs (95% CI)] for incident MetS. Subgroups
      were determined by high or normal 1-hr PG (cut-off: 155 mg/dL) and 2-hr PG (cut
      off: 140 mg/dL). Results: Compared to NG, the risk of MetS increased
      proportionally to the level of 1-hr PG and 2-hr PG, independently of the number
      of baseline metabolic components. Even within individuals with normoglycemia,
      elevated post-load glucose above specific levels (1-hr PG>=115 mg/dL and 2-hr
      PG>=100mg/dL) was significantly associated with the increased risk of MetS. In
      subgroup analysis, adjusted HRs for MetS was higher in group with high 1-hr PG
      and normal 2-hr PG [1.53 (1.35 - 1.74)] than group with normal 1-hr PG and high 2
      hr PG [1.32 (1.02 - 1.70)]. Conclusion: Elevated 1-hr PG and 2-hr PG
      significantly associate with the increased risk for MetS. 1-hr PG was superior to
      2-hr PG in predicting MetS.

PMID- 30239752
TI  - Biallelic mutations in human NHLRC2 enhance myofibroblast differentiation in
      FINCA disease.
AB  - The development of tissue fibrosis is complex and at the present time, not fully
      understood. Fibrosis, neurodegeneration and cerebral angiomatosis (FINCA disease)
      have been described in patients with mutations in NHL repeat-containing protein 2
      (NHLRC2). However, the molecular functions of NHLRC2 are uncharacterized. Herein,
      we identified putative interacting partners for NHLRC2 using proximity-labeling
      mass spectrometry. We also investigated the function of NHLRC2 using immortalized
      cells cultured from skin biopsies of FINCA patients and normal fibroblasts with
      NHLRC2 knock-down and NHLRC2 overexpressing gene modifications. Transmission
      electron microscopy analysis of immortalized cell cultures from three FINCA
      patients demonstrated multilamellar bodies and distinctly organized vimentin
      filaments. Additionally, two of three cultures derived from patient skin biopsies
      contained cells that exhibited features characteristic of myofibroblasts.
      Altogether, the data presented in this study show for the first time that NHLRC2
      is involved in cellular organization through regulation of the cytoskeleton and
      vesicle transport. We conclude that compound heterozygous p.Asp148Tyr and
      p.Arg201GlyfsTer6 mutations in NHLRC2 lead to severe tissue fibrosis in humans by
      enhancing the differentiation of fibroblasts to myofibroblasts.

PMID- 30239753
TI  - High efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults with a
      CYP2B6 516 TT genotype on anti-TB treatment.
AB  - Objectives: To report the efavirenz serum concentrations in TB/HIV-coinfected
      Ugandan adults on concomitant anti-TB treatment and analyse factors associated
      with elevated concentrations in this specific population. Methods: Serum
      efavirenz concentrations in TB/HIV-coinfected Ugandan adults on efavirenz-based
      ART (600 mg daily) were measured onsite at 2, 8, 12 and 24 weeks of concomitant
      anti-TB treatment, including rifampicin. Genetic analysis was done
      retrospectively through real-time PCR by allelic discrimination (CYP2B6 516G>T,
      rs3745274). Univariable and multivariable logistic regression analyses were done
      to assess factors potentially associated with elevated efavirenz serum
      concentrations. Results: A total of 166 patients were included in the analysis.
      The median age was 34 (IQR = 30-40) years, 99 (59.6%) were male, the median CD4
      cell count was 195 (IQR = 71-334) cells/mm3 and the median BMI was 19 (IQR = 17.6
      21.5)  kg/m2. Almost half of all patients (82, 49.4%) had at least one efavirenz
      serum concentration above the reference range of 4 mg/L. The serum efavirenz
      concentrations of patients with genotype CYP2B6 516 TT were consistently above 4
      mg/L and significantly higher than those of patients with GG/GT genotypes: CYP2B6
      516 TT 9.6 mg/L (IQR = 7.3-13.3) versus CYP2B6 516 GT 3.4 mg/L (IQR = 2.1-5.1)
      and CYP2B6 516 GG 2.6 mg/L (IQR = 1.3-4.0) (Wilcoxon rank-sum test: P < 0.0001).
      Conclusions: A large proportion of our study participants had at least one
      efavirenz serum concentration >4 mg/L. The CYP2B6 516 TT genotype was the
      strongest predictor of high concentration. Physicians should be vigilant that
      efavirenz serum concentrations may be elevated in patients on concomitant anti-TB
      treatment and that individualized care is warranted whenever possible.

PMID- 30239755
TI  - Letter to the Editor: "Hemodynamic Effects of Glucagon: A Literature Review".

PMID- 30239754
TI  - Mathematical modelling of trastuzumab-induced immune response in an in vivo
      murine model of HER2+ breast cancer.
AB  - The goal of this study is to develop an integrated, mathematical-experimental
      approach for understanding the interactions between the immune system and the
      effects of trastuzumab on breast cancer that overexpresses the human epidermal
      growth factor receptor 2 (HER2+). A system of coupled, ordinary differential
      equations was constructed to describe the temporal changes in tumour growth,
      along with intratumoural changes in the immune response, vascularity, necrosis
      and hypoxia. The mathematical model is calibrated with serially acquired
      experimental data of tumour volume, vascularity, necrosis and hypoxia obtained
      from either imaging or histology from a murine model of HER2+ breast cancer.
      Sensitivity analysis shows that model components are sensitive for 12 of 13
      parameters, but accounting for uncertainty in the parameter values, model
      simulations still agree with the experimental data. Given theinitial conditions,
      the mathematical model predicts an increase in the immune infiltrates over time
      in the treated animals. Immunofluorescent staining results are presented that
      validate this prediction by showing an increased co-staining of CD11c and F4/80
      (proteins expressed by dendritic cells and/or macrophages) in the total tissue
      for the treated tumours compared to the controls ($p < 0.03$). We posit that the
      proposed mathematical-experimental approach can be used to elucidate driving
      interactions between the trastuzumab-induced responses in the tumour and the
      immune system that drive the stabilization of vasculature while simultaneously
      decreasing tumour growth-conclusions revealed by the mathematical model that were
      not deducible from the experimental data alone.

PMID- 30239756
TI  - Human Flourishing and Integrated Care Models: The Development of the Flourish
      Index.
AB  - Background and Objectives: In evaluating integrated care models, traditional
      quality measures do not account for functional and quality of life factors,
      affecting older adults with multiple chronic conditions. The objective of this
      study was the development and validation of the Flourish Index (FI), an
      instrument to evaluate integrated care, using a determinants of health model.
      Research Design and Methods: The study took place within the evaluation study of
      the Flourish Model (FM). The FM provides care coordination services using an
      integrated primary care and community-based services model. Baseline data from 70
      older adults were used in the validation study. Twenty-seven quality of care
      indicators within six determinants of health, namely biological, psychological,
      individual health behaviors, health services, environmental, and social, formed
      part of the FI. Results: Categorical principal components analysis showed a 5
      dimensional structure with psychological determinants loading on the biological
      determinants of health. Internal consistency (Cronbach's alpha) for the
      determinants was as follows: biological/psychological = 0.73, individual = 0.58,
      environmental = 0.62, health services = 0.65, social = 0.67, total score = 0.97.
      Sensitivity to change was shown for the total FI score (F1,22 = 8.82, p = .01)
      and social (F1,22 = 5.82, p = .02), with a trend toward sensitivity for
      individual health behaviors (F1,22 = 3.95, p = .06) and health services (F1,22 =
      3.26, p = .09). Discussion and Implications: The preliminary analysis of the FI
      shows promise for the usability of the index to provide insight into the
      fundamental challenges of aging. It brings greater clarity in caring for older
      adults and supports quality evaluation of integrated care coordination models.

PMID- 30239758
TI  - Letter to the Editor: One-hour post-load hyperglycemia: implications for
      prediction and prevention of type 2 diabetes.

PMID- 30239757
TI  - Effects of Pitavastatin on Insulin Sensitivity and Liver Fat: A Randomized
      Clinical Trial.
AB  - Context: 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins)
      are widely prescribed. Statins may have important metabolic effects on insulin
      sensitivity and liver fat, but limited studies have assessed these effects by
      using euglycemic hyperinsulinemic clamp, stable isotopes, and 1H magnetic
      resonance spectroscopy (MRS) for liver fat quantification. Objective: To study
      the effects of pitavastatin on hepatic fat and insulin sensitivity. Design: Six
      month, double-blind, randomized, placebo-controlled trial. Setting: Academic
      clinical research center in Boston, Massachusetts. Participants: Overweight,
      insulin-resistant men aged 40 to 65 years who had not received statin therapy for
      >=1 year. Interventions: Pitavastatin 4 mg or placebo daily. Outcome: The primary
      endpoints were changes in insulin sensitivity measured by euglycemic
      hyperinsulinemic clamp and liver fat measured by 1H MRS. Results: Pitavastatin
      showed no effect on endogenous glucose production (DeltaRa glucose 0.07 +/- 0.07
      vs 0.04 +/- 0.07 mg/kg/min, pitavastatin vs placebo, P = 0.76) or insulin
      stimulated glucose uptake during "low dose" (DeltaM 0.1 +/- 0.1 vs -0.3 +/- 0.2
      mg/kg/min, P = 0.11) and "high dose" (DeltaM -0.5 +/- 0.3 vs -0.7 +/- 0.4
      mg/kg/min, P = 0.70) euglycemic hyperinsulinemic clamps. There was also no effect
      of pitavastatin on fasting glucose, HbA1c, and 2-hour glucose after 75-g glucose
      challenge. There was also no change in liver fat fraction (-1 +/- 1 vs -0 +/- 1%,
      P = 0.56). Conclusion: Compared with placebo, pitavastatin did not affect hepatic
      or whole-body insulin sensitivity, and it did not reduce liver fat.

PMID- 30239759
TI  - Epigenetic changes in preterm birth placenta suggest a role for ADAMTS genes in
      spontaneous preterm birth
AB  - PTB affects approximately 1 in 10 pregnancies and contributes to approximately
      50% of neonatal mortality. However, despite decades of research, little is
      understood about the etiology of Preterm Birth (PTB), likely due to the
      multifactorial nature of the disease. In this study, we examined preterm and term
      placentas, from unassisted conceptions and those conceived using in vitro
      fertilization (IVF). IVF increases the risk of PTB and causes epigenetic change
      in the placenta and fetus, therefore we utilized these patients as a unique
      population with a potential common etiology. We investigated genome-wide DNA
      methylation in placentas from term-IVF, preterm-IVF, term-Control (unassisted
      conception) and preterm-Control pregnancies and discovered epigenetic
      dysregulation of multiple genes involved in cell migration, including members of
      the ADAMTS family, ADAMTS12 and ADAMTS16. These genes function in extracellular
      matrix regulation and tumor cell invasion, processes replicated by invasive
      trophoblasts (EVTs) during early placentation. Though expression was similar
      between term and preterm placentas, we found that both genes demonstrate high
      expression in first and second trimester placenta, specifically in EVTs and
      syncytiotrophoblasts. When we knocked down ADAMTS12 or ADAMTS16 in vitro, there
      was poor EVT invasion and reduced matrix metalloproteinase activity, reinforcing
      their critical role in placentation. In conclusion, utilizing a population at
      high risk for PTB, we have identified a role for ADAMTS gene methylation in
      regulating early placentation and susceptibility to PTB.

PMID- 30239760
TI  - Physiology of Glycemic Recovery and Stabilization After Hyperinsulinemic
      Euglycemic Clamp in Healthy Subjects.
AB  - Background: The hyperinsulinemic euglycemic clamp (HEC) is the gold standard for
      measuring insulin sensitivity, but glycemic recovery and stabilization after the
      procedure have not been well studied. Here, we assessed the physiological
      determinants of postclamp recovery. Methods: We analyzed data from 207 healthy
      subjects [102 African American (AA) and 105 European American (EA)] who underwent
      HEC in the Pathobiology of Prediabetes in a Biracial Cohort study. At the end of
      HEC, insulin infusion was stopped, and dextrose (20%) infusion was tapered and
      stopped when plasma glucose stabilized >=20 mg/dL above the preclamp value (~100
      mg/dL). Glucose recovery time (GRT) was defined as the interval from cessation of
      insulin infusion to discontinuation of dextrose infusion. Insulin clearance was
      calculated under basal and clamp conditions. Results: The mean (+/- SD) age and
      body mass index were 46.3 +/- 9.96 years and 30.7 +/- 8.43 kg/m2, respectively.
      Plasma glucose (mg/dL) was 92.2 +/- 6.26 preclamp and 124.2 +/- 26.9 postclamp.
      The median GRT (minutes) was 65 (range, 30 to 270); mean GRT was 77.1 +/- 42.7
      (men: 82.9 +/- 45.5; women: 74.4 +/- 42.3; AA, 82.0 +/- 49.6; EA, 72.3 +/- 34.2;
      P > 0.1 for sex or race). The 90th percentile for GRT was 119 minutes. In
      regression models, significant predictors of GRT were age (P = 0.03), weight (P =
      0.009), 2-hour plasma glucose (P = 0.0002), insulin sensitivity (P = 0.03),
      disposition index (P = 0.017), and basal insulin clearance (P = 0.02).
      Conclusions: In our biracial cohort, glycemic recovery after hyperinsulinemic
      clamp was independent of sex or race but was significantly predicted by age,
      weight, and glucose tolerance and by insulin sensitivity, secretion, and
      clearance. We recommend that monitoring be maintained for ~2 hours postclamp to
      ensure adequate glycemic stabilization.

PMID- 30239761
TI  - A Call to Action: Pregnant Women In-Deed Require Vitamin D Supplementation for
      Better Health Outcomes.

PMID- 30239763
TI  - Is gambling an emerging public health issue for Wales, UK?
AB  - Background: Not all gambling exposes people to the same level of harm. Harm from
      gambling is found at the individual, social (family and friends) and community
      levels. This includes financial hardship, psychological distress and
      interpersonal conflict or relationship breakdown. The harm from gambling to wider
      society includes fraud, theft, loss of productivity in the workforce and the cost
      of treating this addiction. The annual estimated excess cost of gambling for
      Wales is between L40 and L70 million. Methods: This study reviews the existing
      data sources and literature to ascertain if gambling is an emerging public health
      issue in Wales. Results: In Wales 61% of adults had gambled in the last year (1.5
      million people). And 1.1% of the population (30 000 people) self-report as having
      a problem with gambling using either the Problem Gambling Severity Index or the
      Diagnostic and Statistical Manual of American Psychiatric Association tools. The
      'ripple effect' of gambling harm can mean friends and family are highly impacted.
      Conclusion: The existing data and literature together with the rapidly evolving
      developments in infrastructure demonstrate that gambling is an emerging public
      health issue in Wales. The impact on families and society warrants population
      level interventions to tackle this public health issue.

PMID- 30239764
TI  - Response to Letter to the Editor: "Hemodynamic Effects of Glucagon: A Literature
      Review".

PMID- 30239766
TI  - The certificate in travel health.

PMID- 30239765
TI  - Influence of risk-organ-based tube current modulation on CT-induced DNA double
      strand breaks in a biological phantom model.
AB  - Techniques for dose reduction in computed tomography (CT) are receiving
      increasing attention. Lowering the tube current in front of the patient, known as
      risk-organ-based tube current modulation (RTM), represents a new approach.
      Physical dose parameters can determine the exposure but are not able to assess
      the biological-X-ray interactions. The purpose of this study was to establish a
      biological phantom model to evaluate the effect of RTM on X-ray-induced DNA
      double-strand breaks (DSBs). In breast phantoms and in the location of the spine
      in an Alderson phantom, isolated human blood lymphocytes were irradiated using a
      128-slice CT scanner. A standard thoracic CT protocol (120 kV, 110 ref. mAs,
      anatomy-based tube current modulation, pitch 0.6, scan length 30 cm) with and
      without RTM was used. X-ray-induced DSBs were quantified in isolated blood
      lymphocytes using immunofluorescence microscopy after staining for the
      phosphorylated histone variant gamma-H2AX. Using RTM, the resulting DNA damage
      reduction was 41% in superficial breast locations (P = 0.0001), 28% in middle
      breast locations (P = 0.0003) and 29% in lower breast locations (P = 0.0001), but
      we found a DNA damage increase of 36% in superficial spine locations (P = 0.0001)
      and of 26% in deep spine locations (P = 0.0001). In summary, we established a
      biological phantom model that is suitable for detecting DNA damage in distinct
      organs. In addition, we were able to show that, using RTM, X-ray-induced DNA
      damage in the breast can be significantly reduced; however, there is a
      significant increase in DSBs in the location of the spine.

PMID- 30239762
TI  - Making Sense of Rodent Models of Anhedonia.
AB  - A markedly reduced interest or pleasure in activities previously considered
      pleasurable is a main symptom in mood disorder and psychosis and is often present
      in other psychiatric disorders and neurodegenerative diseases. This condition can
      be labeled as "anhedonia," although in its most rigorous connotation the term
      refers to the lost capacity to feel pleasure that is one aspect of the complex
      phenomenon of processing and responding to reward. The responses to rewarding
      stimuli are relatively easy to study in rodents, and the experimental conditions
      that consistently and persistently impair these responses are used to model
      anhedonia. To this end, long-term exposure to environmental aversive conditions
      is primarily used, and the resulting deficits in reward responses are often
      accompanied by other deficits that are mainly reminiscent of clinical depressive
      symptoms. The different components of impaired reward responses induced by
      environmental aversive events can be assessed by different tests or protocols
      that require different degrees of time allocation, technical resources, and
      equipment. Rodent models of anhedonia are valuable tools in the study of the
      neurobiological mechanisms underpinning impaired behavioral responses and in the
      screening and characterization of drugs that may reverse these behavioral
      deficits. In particular, the antianhedonic or promotivational effects are
      relevant features in the spectrum of activities of drugs used in mood disorders
      or psychosis. Thus, more than the model, it is the choice of tests that is
      crucial since it influences which facets of anhedonia will be detected and should
      be tuned to the purpose of the study.

PMID- 30239768
TI  - Performance of the Black Soldier Fly (Diptera: Stratiomyidae) on Vegetable
      Residue-Based Diets Formulated Based on Protein and Carbohydrate Contents.
AB  - The black soldier fly [Hermetia illucens L. (Diptera: Stratiomyidae)] can be
      sustainably reared on organic waste streams and thereby provide a novel animal
      protein source for animal feed. Black soldier fly's performance and body
      composition depend to a large extent on the nutrient composition of the waste
      stream. Black soldier fly larvae were fed on four diets consisting of vegetable
      by-products from the food industry. All four diets contained dried distiller's
      grains with solubles plus one or two other main ingredients; for diet 1 the
      additional ingredient was grape pulp; diet 2: potato peels; diet 3: bean seeds;
      and diet 4: cabbage leaves plus old bread. The diets were formulated based on an
      optimal summed protein and carbohydrate (P+C) concentration resulting from
      previous experiments and a 1:2 protein:carbohydrate (P:C) ratio. We quantified
      both larval and adult performance. Diet 4 was the best performing vegetable waste
      based diet. In a follow-up experiment, we re-formulated diet 4 to have P:C ratios
      of 1:2 or 1:3 and 40 or 47% dry matter of P+C. In the first experiment, although
      there were differences in larval performance among the diets, all diets supported
      a higher larval performance than reported previously, with diet 4 having 47% P+C
      being the best performing diet. We infer that not only total macronutrient
      content but also nutritional quality of proteins and carbohydrates affected
      performance. In the second experiment, the two vegetable residue-based larval
      diets resulted in similar larval and adult performance. High dietary protein
      resulted in increases in larval crude fat content.

PMID- 30239767
TI  - Early Bacille Calmette-Guerin vaccination, hospitalizations and hospital deaths:
      Analysis of a secondary outcome in three randomized trials from Guinea-Bissau.
AB  - Objective: To examine effects of early Bacille Calmette-Guerin (BCG) vaccination
      on the risk, cause and severity of infant hospitalizations. Design: Analysis of
      three trials randomizing low-weight neonates to early-BCG(intervention) versus no
      BCG(usual practice in low-weight neonates, control), with hospitalizations as
      secondary outcome. Methods: Hospitalization data was collected at the pediatric
      ward of the National Hospital. Effects of BCG on hospitalization risk were
      assessed in Cox-models providing overall and major disease-group incidence rate
      ratios(IRRs). Severity was assessed by in-hospital case-fatality rates and
      compared by group as cohort study risk ratios(RRs). Results: Among 6,583 infants
      (3,297 BCG; 3,286 controls), there were 908 infant hospitalizations (450 BCG; 458
      controls) and 135 in-hospital deaths (56 BCG; 79 controls). The neonatal(28days),
      6-week and infant(1year) BCG versus control hospitalization IRRs were 0.97(95% CI
      0.72-1.31), 0.95(0.73-1.24) and 0.96(0.84-1.10). Corresponding BCG versus control
      case-fatality RRs were 0.58(0.35-0.94), 0.56(0.35-0.90) and 0.72(0.53-0.99). BCG
      tended to reduce neonatal and infant sepsis hospitalization rates, IRRs being
      0.75(0.50-1.13) and 0.78(0.55-1.11), and reduced in-hospital neonatal sepsis
      mortality, RR=0.46(0.22-0.98). There were no confirmed tuberculosis
      hospitalizations. Conclusion: BCG did not affect hospitalization rates but
      reduced in-hospital mortality significantly, primarily by preventing fatal cases
      of sepsis. The observed beneficial effects of BCG on in-hospital mortality were
      entirely non-specific.

PMID- 30239769
TI  - Cascade Genetic Testing of Relatives for Hereditary Cancer Risk: Results of an
      Online Initiative.
AB  - In cascade testing, genetic testing for an identified familial pathogenic variant
      extends to disease-free relatives to allow genetically targeted disease
      prevention. We evaluated the results of an online initiative in which carriers of
      1 of 30 cancer-associated genes, or their first-degree relatives, could offer low
      cost testing to at-risk first-degree relatives. In the first year, 1101
      applicants invited 2280 first-degree relatives to undergo genetic testing. Of
      invited relatives, 47.5% (95% confidence interval [CI] = 45.5 to 49.6%) underwent
      genetic testing, and 12.0% (95% CI = 9.2 to 14.8%) who tested positive continued
      the cascade by inviting additional relatives to test. Of tested relatives, 4.9%
      (95% CI = 3.8 to 6.1%) had a pathogenic variant in a different gene from the
      known familial one, and 16.8% (95% CI = 14.7 to 18.8%) had a variant of uncertain
      significance. These results suggest that an online, low-cost program is an
      effective approach to implementing cascade testing, and that up to 5% of the
      general population may carry a pathogenic variant in 1 of 30 cancer-associated
      genes.

PMID- 30239770
TI  - Prevalence and course of endocrinopathy in POEMS syndrome.
AB  - Context: POEMS syndrome is a rare multisystem disorder characterised by
      polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative
      disorder and skin changes among other features. Objective: To describe the
      prevalence and course of the endocrine dysfunction in the context of POEMS.
      Design: Cohort study with systematic review of the endocrinopathy in POEMS.
      Setting: 75 patients with POEMS were evaluated by the multidisciplinary team at
      our tertiary specialist centre. Patients: Endocrine data was available for 59
      patients who attended the clinic from 06/1999 to 05/2018. Interventions: All
      patients had regular endocrine screening including testing for diabetes,
      pituitary and thyroid dysfunction and assessment of bone metabolism. Main Outcome
      Measure: Prevalence and survival time to develop endocrinopathy in POEMS.
      Results: Thirty-four (63%) patients presented with an endocrinopathy at point of
      POEMS diagnosis and 54 (92%) had at least one endocrine abnormality at follow-up.
      The median follow-up was 4.4[1.5, 7.9] years. The most common endocrine
      abnormality was hypogonadism in 68%, followed by hyperprolactinaemia (56%),
      hypothyroidism (54%), abnormal glucose metabolism (24%), adrenal insufficiency
      (17%) and high IGF-1 levels (15%). Spontaneous resolution of endocrine
      abnormalities at the end of follow-up was observed: 14% in hypogonadism, 42% in
      hyperprolactinaemia, 34% in hypothyroidism and 38% in high IGF-1 levels.
      Conclusions: Endocrinopathy was found in 63% of patients at diagnosis and in 92%
      of patients during follow-up in our cohort, therefore patients with POEMS should
      be systematically assessed for endocrinopathy. The most common deficiencies were
      hypogonadism and hypothyroidism, however normalisation of the endocrinopathy can
      occur so on-going treatment should remain under review.

PMID- 30239771
TI  - Four-dimensional flow magnetic resonance imaging analysis before and after
      thoracic endovascular aortic repair of chronic type B aortic dissection.
AB  - OBJECTIVES: The purpose of this study was to calculate the changes in the blood
      flow direction and volume in the aortic lumen and at the entry and re-entry sites
      using 4-dimensional (4D) phase-contrast magnetic resonance imaging (MRI) after
      performing entry closure with thoracic endovascular aortic repair for chronic
      DeBakey IIIb aortic dissection. METHODS: Aortic blood flow was analysed at 3
      phases with 4D phase-contrast MRI in a single therapeutic DeBakey IIIb aortic
      dissection case. RESULTS: Primary entry was in the distal arch, and there were 4
      re-entry sites downstream in the diaphragm. Preoperatively, the entry site formed
      a large antegrade flow (1082 ml/min) to the 4 re-entry sites, but soon after the
      closure of the entry site, re-entry sites 1 through 3 became a new entry site
      whose flow pattern changed retrogradely, resulting in increased volume in the
      false lumen in the acute phase, whereas the flow at the previous re-entry sites
      from the true lumen to the false lumen decreased gradually, resulting in aortic
      remodelling with a reduction in the size of the false lumen: the preoperative,
      postoperative and 6-month postoperative mean flow volumes (ml/min) were 23, 254
      and 173 at re-entry site 1; 59, 887 and 279 at re-entry site 2; and 303, 608 and
      103 at re-entry site 3. The changes in the flow volume of the false lumen
      followed a similar trend expect for the area around the abdominal aorta.
      CONCLUSIONS: The volume of flow at the entry site was high, and closure of the
      primary entry site during thoracic endovascular aortic repair is very important.
      These changes in the flow volume of the re-entry sites and the false lumen may
      affect volume changes in the false lumen.

PMID- 30239772
TI  - Eosinophil-derived neurotoxin enhances airway remodeling in eosinophilic chronic
      rhinosinusitis and correlates with disease severity.
AB  - Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis
      (CRS) that is characterized by intractable nasal polyp formation. Eosinophil
      derived neurotoxin (EDN) is an eosinophil granule protein that is closely related
      to allergic inflammation, but the pathological implications of EDN in ECRS remain
      unknown. In this study, we evaluated the function of EDN in ECRS pathogenesis and
      assessed its potential as a disease activity marker. Serum EDN levels were
      significantly higher in patients with ECRS than in those with other nasal and
      paranasal diseases, and were positively correlated with clinical disease
      activity. Production of EDN from isolated human eosinophils was induced by
      stimulation with IL-5 in vitro. Human nasal epithelial cells (HNEpCs) were
      stimulated with EDN, and the resultant changes in gene expression were detected
      by RNA sequencing. Pathway analysis revealed that the major canonical pathway
      affected by EDN stimulation was "regulation of the epithelial-mesenchymal
      transition (EMT) pathway;" the only gene in this pathway to be up-regulated was
      matrix metalloproteinase 9 (MMP9). Consistent with this, immunostaining analysis
      revealed intense staining of both EDN and MMP-9 in nasal polyps from patients
      with ECRS. In conclusion, our data demonstrate that serum EDN level is a useful
      marker for the evaluation of ECRS severity. Furthermore, EDN induces production
      of MMP-9 from the nasal epithelium, which may be involved in the pathogenesis of
      ECRS.

PMID- 30239773
TI  - Combining Tumor Microenvironment Modulating Nanoparticles with Doxorubicin to
      Enhance Chemotherapeutic Efficacy and Boost Antitumor Immunity.
AB  - Background: Tumor microenvironment (TME) and associated multiple factors are
      found to contribute to the failures in cancer therapies, including chemo- and
      immunotherapy. Here we report a new multimodal strategy that uses a bioreactive
      multifunctional hybrid polymer-lipid encapsulated manganese dioxide nanoparticle
      (PLMD NP) system to remodel the TME, suppress drug resistance factors, reverse
      immunosuppressive conditions, and enhance chemotherapy efficacy. Methods: The
      influence of PLMD NPs on enhancing cellular uptake in EMT6 mouse breast cancer
      cells and tumor penetration of doxorubicin (DOX) in EMT6 orthotopic breast tumor
      mouse model was evaluated using confocal microscopy (n = 3-4).
      Immunohistochemistry was employed to examine the effect of PLMD NPs on
      downregulating hypoxia-induced drug resistance proteins and anticancer activity
      of DOX (n = 3-4). The efficacy of the combination therapy with PLMD NPS and DOX
      was assessed in murine EMT6 (n = 15-23) and 4T1 (n = 7) orthotopic breast tumor
      mouse models. Rechallenge and splenocyte transfer were performed to validate the
      stimulation of adaptive tumor immunity in the surviving mice. Results: PLMD NPs
      enhanced intratumoral penetration and efficacy of DOX, and reduced intratumoral
      expression of P-glycoprotein, p53, and carbonic anhydrase IX by 74.5%, 38.0%, and
      58.8% vs saline control, respectively. Combination treatment with PLMD NPs and
      DOX increased the number of tumor-infiltrated CD8+ T cells and resulted in up to
      60.0% complete tumor regression. Of naive mice (n = 7) that received splenocytes
      from the PLMD+DOX-treated surviving mice, 57.1% completely suppressed tumor
      growth whereas 100% of mice that received splenocytes from DOX-treated mice (n =
      3) and the control group (n = 7) showed rapid tumor growth. Conclusions: The
      clinically suitable PLMD NPs can effectively downregulate TME-associated drug
      resistance and immunosuppression. The combination therapy with PLMD NPs and DOX
      is a multimodal and translational treatment approach for enhancing
      chemotherapeutic efficacy and boosting antitumor immunity.

PMID- 30239774
TI  - Implementation of the Stopping Elderly Accidents, Deaths, and Injuries Initiative
      in Primary Care: An Outcome Evaluation.
AB  - Background and Objectives: Older adult falls pose a growing burden on the U.S.
      health care system. The Centers for Disease Control and Prevention's Stopping
      Elderly Accidents, Deaths, and Injuries (STEADI) initiative was developed as a
      multifactorial approach to fall prevention that includes screening for fall risk,
      assessing for modifiable risk factors, and prescribing evidence-based
      interventions to reduce fall risk. The purpose of this study was to determine the
      impact of a STEADI initiative on medically treated falls within a large health
      care system in Upstate New York. Research Design and Methods: This cohort study
      classified older adults who were screened for fall risk into 3 groups: (a) At
      risk and no Fall Plan of Care (FPOC), (b) At-risk with a FPOC, and (c) Not-at
      risk. Poisson regression examined the group's effect on medically treated falls
      when controlling for other variables. The sample consisted of 12,346 adults age
      65 or older who had a primary care visit at one of 14 outpatient clinics between
      September 11, 2012, and October 30, 2015. A medically treated fall was defined as
      a fall-related treat-and-release emergency department visit or hospitalization.
      Results: Older adults at risk for fall with a FPOC were 0.6 times less likely to
      have a fall-related hospitalization than those without a FPOC (p = .041), and
      their postintervention odds were similar to those who were not at risk.
      Discussion and Implications: This study demonstrated that implementation of
      STEADI fall risk screening and prevention strategies among older adults in the
      primary care setting can reduce fall-related hospitalizations and may lower
      associated health care expenditures.

PMID- 30239775
TI  - A role for the Tgf-beta/Bmp co-receptor Endoglin in the molecular oscillator that
      regulates the hair follicle cycle.
AB  - The hair follicle is a biological oscillator that alternates growth, regression,
      and rest phases driven by the sequential activation of the
      proliferation/differentiation programs of resident stem cell populations. The
      activation of hair follicle stem cell niches and subsequent entry into the
      growing phase is mainly regulated by Wnt/beta-catenin signalling, while
      regression and resting phases are mainly regulated by Tgf-beta/Bmp/Smad activity.
      A major question still unresolved is the nature of the molecular switch that
      dictates the coordinated transition between both signalling pathways. Here we
      have focused on the role of Endoglin (Eng), a key co-receptor for members of the
      Tgf-beta/Bmp family of growth factors.Using an Eng haploinsufficient mouse model,
      we report that Eng is required to maintain a correct follicle cycling pattern and
      for an adequate stimulation of hair follicle stem cell niches. We further report
      that beta-catenin binds to the Eng promoter depending on Bmp signalling.
      Moreover, we show that beta-catenin interacts with Smad4 in a Bmp/Eng-dependent
      context and both proteins act synergistically to activate Eng promoter
      transcription. These observations point to the existence of a growth/rest
      switching mechanism in the hair follicle that is based on an Eng-dependent
      feedback crosstalk between Wnt/beta-catenin and Bmp/Smad signals.

PMID- 30239776
TI  - Effects of pH manipulation, CatSper stimulation and Ca2+-store mobilization on
      [Ca2+]i and behaviour of human sperm.
AB  - STUDY QUESTION: How do the alkaline pH, progesterone and 4-aminopyridine interact
      in their effects on human sperm? SUMMARY ANSWER: Behaviour of human sperm
      (proportion of hyperactivated cells and motility kinematics) were related
      directly to [Ca2+]i irrespective of pH or the agonist applied. WHAT IS KNOWN
      ALREADY?: CatSper channels of human sperm, which are central to generation of
      sperm [Ca2+]i signals and induction of hyperactivated motility, are activated by
      intracellular alkalinization and progesterone. Progesterone (P4) is much less
      effective than 4-aminopyridine (4-AP) (which mobilizes stored Ca2+ but also
      raises pHi) as an inducer of hyperactivation. STUDY DESIGN, SIZE, DURATION: This
      was a laboratory study, spanning ~18 months that used 15 sperm donors and
      involved more than 100 separate experiments. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: Semen donors and patients were recruited in accordance with local ethics
      approval (ERN_12-0570R). [Ca2+]i responses of suspended cell populations were
      examined by fluorimetric recording and motility parameters assessed by computer
      assisted sperm analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Increasing pHo from
      7.4 to 8.5 raised pHi (from 6.9 to 7.2) and significantly increased both [Ca2+]i
      and the proportion of hyperactivated cells. Stimulation of cells with P4 (1 nM-20
      MUM) induced a biphasic (transient and plateau) increase in [Ca2+]i. The [Ca2+]i
      increase was of similar amplitude and dose-dependency at pHo = 7.4 and pHo = 8.5.
      4-aminopyridine (0.2-5 mM) induced a biphasic [Ca2+]i increase that was dose
      dependent across the entire range tested and was strongly enhanced at pH 8.5.
      Motility was assessed 300 s post-stimulation, during the plateau phase of the
      progesterone and 4-AP-induced [Ca2+]i responses. Progesterone had only a small
      effect on hyperactivated motility even at the highest dose used (20 MUM; < 5%
      increase in the proportion of cells classified as hyperactivated) which was
      insensitive to pHo. 4-Aminopyridine potently stimulated hyperactivated motility,
      this effect being dose-dependent and greatly enhanced at pHo = 8.5. The
      relationship between [Ca2+]i (fluorescence of fluo4) and proportion of
      hyperactivated cells, irrespective of pHo, agonist or dose, was fitted by a
      single curve (second order polynomial; R2 = 0.96). Similar analysis of
      curvilinear velocity (VCL) and amplitude of lateral head displacement (ALH)
      showed a linear relationship to [Ca2+]i (R2 > 0.9). LIMITATIONS, REASONS FOR
      CAUTION: This was an in-vitro study and caution must be taken when extrapolating
      these results to in vivo regulation of sperm. Though controls indicate that
      saturation of fluo4 did not affect the findings, at the highest doses of
      progesterone the true amplitude of the [Ca2+]i transient may not have been
      reported by the dye. WIDER IMPLICATIONS OF THE FINDINGS: These findings indicate
      that (i) activation of human sperm CatSper by progesterone (and presumably other
      ligands that act similarly) and consequent acquisition of hyperactivated motility
      is not significantly enhanced by intracellular alkalinization; (ii) VCL, ALH and
      hyperactivation are directly related to [Ca2+]i, irrespective of the mechanism by
      which Ca2+ is mobilized, and the ability of stimuli to induce prolonged [Ca2+]i
      elevation (as occurs upon mobilization of stored Ca2+) determines the observed
      effect on cell behaviour. STUDY FUNDING/COMPETING INTEREST(S): CA was supported
      by the Nigerian government (Tertiary Education Trust (TET) Fund). The authors
      have no conflicts of interest.

PMID- 30239777
TI  - Can health promotion also do harm?

PMID- 30239778
TI  - Live birth rate and obstetric complications following the hysteroscopic
      management of intrauterine adhesions including Asherman syndrome.
AB  - STUDY QUESTION: What are the live birth rate and risks of obstetric complications
      following the surgical management of intrauterine adhesions (IUA) such as
      Asherman syndrome (AS)? SUMMARY ANSWER: The live birth rate is 63.7%, and
      obstetric complications including placentation issues, prematurity and postpartum
      hysterectomy require that pregnancies in women after treatment for IUA should be
      considered moderate to high risk. WHAT IS KNOWN ALREADY: Studies reviewing short
      term surgical, menstrual and fertility outcomes following hysteroscopic
      management are reassuring, with success correlated to the severity of IUA. There
      are limited data reporting live birth, neonatal and maternal complications. STUDY
      DESIGN, SIZE, DURATION: This retrospective study included all women treated for
      IUA by hysteroscopic synechiolysis under fluoroscopic guidance in two tertiary
      University-affiliated hospitals. All women reported at least one pre-treatment
      symptom including menstrual dysfunction, subfertility or pelvic pain and intended
      to become pregnant post-treatment. Survival curve analysis was performed for time
      to pregnancy, and obstetric data were collated from a National Obstetric Database
      for delivery and neonatal outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: A
      total of 154 women were included in the study. Surgical intervention involved
      hysteroscopic synechiolysis under fluoroscopic guidance until cavity restoration
      was confirmed. Questionnaires regarding fertility and its outcomes were sent to
      all women undergoing surgery, with analysis of menstrual, fertility rates and
      outcomes of those pregnancies including risks and complications to the woman and
      the offspring. MAIN RESULTS AND THE ROLE OF CHANCE: Women were followed up for a
      minimum of 1 year (range: 1-14 years) from index surgery. The chance of pregnancy
      was 98/124 (79.0% CI: 63.6, 83.1%) in women wishing to conceive and the chance of
      a live birth was 79/124 (63.7% CI: 51.3, 70.7%). The chance of a miscarriage was
      29/124 (23.4% CI: 18.8, 37.1%). There were 93 live births in 79 women following
      surgery, with detailed obstetric data available for 85 of these births. They were
      complicated by abnormal placentation in 15/85 (17.6% CI: 13.0, 30.2%), postpartum
      hysterectomy in 4/85 (4.7% CI: -0.4, 7.0%), and prematurity in 25/85 (29.4% CI:
      17.0, 35.3%) women. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of
      the study and extended follow-up time may cause selection and recall bias,
      however, pregnancy and its outcomes-particularly in women with problems of
      subfertility-are frequently key milestones, with birthdates readily recalled.
      Menstrual outcomes are more likely to be subject to recall bias. WIDER
      IMPLICATIONS OF THE FINDINGS: Our surgical data are similar to the published
      literature with reassuring short-term outcomes for menstruation and cavity
      reconstruction following surgery for IUA. Long-term outcomes including pregnancy
      rates were higher than published data, however, the obstetric and neonatal
      complication rates were increased, indicating a continuation of risk beyond
      infertility and into pregnancy. An altered biochemical or vascular environment is
      a possible explanation for impaired implantation resulting in poorer reproductive
      obstetric and neonatal outcomes. The relative rarity of IUA-particularly severe
      disease-makes prospective data collection difficult. Our data suggest that women
      with IUA should be treated as moderate-high risk obstetric patients in subsequent
      pregnancy and counselled appropriately. STUDY FUNDING/COMPETING INTEREST(S): No
      funding and no competing interests.

PMID- 30239779
TI  - A nonsense mutation in Myelin Protein Zero causes congenital hypomyelination
      neuropathy through altered P0 membrane targeting and gain of abnormal function.
AB  - Protein Zero (P0) is the major structural protein in peripheral myelin and
      mutations in the Myelin Protein Zero (Mpz) gene produce wide ranging hereditary
      neuropathy phenotypes. To gain insight in the mechanisms underlying a
      particularly severe form, congenital hypomyelination (CH), we targeted mouse Mpz
      to encode P0Q215X, a nonsense mutation associated with the disease, that we show
      escapes nonsense mediated decay and is expressed in CH patient nerves. The knock
      in mice express low levels of the resulting truncated protein, producing a milder
      phenotype when compared to patients, allowing to dissect the subtle pathogenic
      mechanisms occurring in otherwise very compromised peripheral myelin. We find
      that P0Q215X does not elicit an unfolded protein response, which is a key
      mechanism for other pathogenic MPZ mutations, but is instead in part aberrantly
      trafficked to non-myelin plasma membranes and induces defects in radial sorting
      of axons by Schwann cells (SC). We show that the loss of the C-terminal YAML
      motif is responsible for P0 mislocalisation, as its addition is able to restore
      correct P0Q215X trafficking in vitro. Lastly, we show that P0Q215X acts through
      dose-dependent gain of abnormal function, as wildtype P0 is unable to rescue the
      hypomyelination phenotype. Collectively, these data indicate that alterations at
      the premyelinating stage, linked to altered targeting of P0, may be responsible
      for CH, and that different types of gain of abnormal function produce the diverse
      neuropathy phenotypes associated with MPZ, supporting future allele-specific
      therapeutic silencing strategies.

PMID- 30239780
TI  - Parasitism of Black-Tailed Prairie Dogs by Linognathoides cynomyis (Phthiraptera:
      Polyplacidae).
AB  - The following study investigates louse parasitism of black-tailed prairie dogs
      (Cynomys ludovicianus (Ord, Rodentia: Sciuridae)) on 20 plots at 13 colonies in
      the short-grass prairie of New Mexico, USA, June-August, 2011-2012. Among 124
      lice collected from 537 prairie dogs during 1,207 sampling events in which
      anesthetized animals were combed for ectoparasites, all of the lice were
      identified as Linognathoides cynomyis (Kim, Phthiraptera: Polyplacidae). Data
      were analyzed under an information-theoretic approach to identify factors
      predicting louse parasitism. Lice were most prevalent on plots with high
      densities of prairie dogs. At the scale of hosts, lice were most abundant on
      prairie dogs in poor body condition (with low mass:foot ratios) and prairie dogs
      harboring large numbers of fleas (Siphonaptera, mostly Oropsylla hirsuta (Baker,
      Siphonaptera: Ceratophyllidae) and Pulex simulans (Baker,Siphonaptera:
      Pulicidae)). Lice have been implicated as supplemental vectors of the primarily
      flea-borne bacterium Yersinia pestis (Yersin, Enterobacteriales: Yersiniaceae), a
      re-emerging pathogen that causes sylvatic plague in prairie dog populations.
      Coparasitism by lice and fleas, as found herein, might enhance plague
      transmission. L. cynomyis deserves attention in this context.

PMID- 30239782
TI  - Evolution in the Dark: Unifying our Understanding of Eye Loss.
AB  - The evolution of eye loss in subterranean, deep sea, and nocturnal habitats has
      fascinated biologists since Darwin wrestled with it in On the Origin of Species.
      This phenomenon appears consistently throughout the animal kingdom, in groups as
      diverse as crustaceans, salamanders, gastropods, spiders, and the well-known
      Mexican cave fish, but the nature, extent, and evolutionary processes behind eye
      loss remain elusive. With the advantage of new imaging, molecular, and
      developmental tools, eye loss has once again become the subject of intense
      research focus. To advance our understanding of eye loss as a taxonomically
      widespread and repeated evolutionary trajectory, we organized a cross
      disciplinary group of researchers working on the historic question, "how does eye
      loss evolve in the dark?." The resulting set of papers showcase new progress made
      in understanding eye loss from the diverse fields of molecular biology,
      phylogenetics, development, comparative anatomy, paleontology, ecology, and
      behavior in a wide range of study organisms and habitats. Through the integration
      of these approaches, methods, and results, common themes begin to emerge across
      the field. For the first time, we hope researchers can exploit this new synthesis
      to identify the broader challenges and key evolutionary questions surrounding eye
      evolution and so-called regressive evolution and collectively work to address
      them in future research.

PMID- 30239781
TI  - Identifying core biological processes distinguishing human eye tissues with
      precise systems-level gene expression analyses and weighted correlation networks.
AB  - The human eye is built from several specialized tissues which direct, capture and
      pre-process information to provide vision. The gene expression of the different
      eye tissues has been extensively profiled with RNA-seq across numerous studies.
      Large consortium projects have also used RNA-seq to study gene expression
      patterning across many different human tissues, minus the eye. There has not been
      an integrated study of expression patterns from multiple eye tissues compared
      with other human body tissues. We have collated all publicly available healthy
      human eye RNA-seq datasets as well as dozens of other tissues. We use this fully
      integrated dataset to probe the biological processes and pan expression
      relationships between the cornea, retina, retinal pigment epithelium (RPE)
      choroid complex, and the rest of the human tissues with differential expression,
      clustering and gene ontology term enrichment tools. We also leverage our large
      collection of retina and RPE-choroid tissues to build the first human weighted
      gene correlation networks and use them to highlight known biological pathways and
      eye gene disease enrichment. We also have integrated publicly available single
      cell RNA-seq data from mouse retina into our framework for validation and
      discovery. Finally, we make all these data, analyses and visualizations available
      via a powerful interactive web application (https://eyeintegration.nei.nih.gov/).

PMID- 30239783
TI  - The Mitochondrial Contribution to Animal Performance, Adaptation, and Life
      History Variation.
AB  - Animals display tremendous variation in their rates of growth, reproductive
      output, and longevity. While the physiological and molecular mechanisms that
      underlie this variation remain poorly understood, the performance of the
      mitochondrion has emerged as a key player. Mitochondria not only impact the
      performance of eukaryotes via their capacity to produce ATP, but they also play a
      role in producing heat and reactive oxygen species and function as a major
      signaling hub for the cell. The papers included in this special issue emerged
      from a symposium titled "Inside the Black Box: The Mitochondrial Basis of Life
      history Variation and Animal Performance." Based on studies of diverse animal
      taxa, three distinct themes emerged from these papers. (1) When linking
      mitochondrial function to components of fitness, it is crucial that mitochondrial
      assays are performed in conditions as close as the intracellular conditions
      experienced by the mitochondria in vivo. (2) Functional plasticity allows
      mitochondria to retain their performance, as well as that of their host, over a
      range of exogenous conditions, and selection on mitochondrial and nuclear-derived
      proteins can optimize the match between the environment and the bioenergetic
      capacity of the mitochondrion. Finally, (3) studies of wild and wild-derived
      animals suggest that mitochondria play a central role in animal performance and
      life history strategy. Taken as a whole, we hope that these papers will foster
      discussion and inspire new hypotheses and innovations that will further our
      understanding of the mitochondrial processes that underlie variation in life
      history traits and animal performance.

PMID- 30239784
TI  - A cost-effectiveness analysis of freeze-only or fresh embryo transfer in IVF of
      non-PCOS women.
AB  - STUDY QUESTION: Is a freeze-only strategy more cost-effective from a patient
      perspective than fresh embryo transfer (ET) after one completed In Vitro
      Fertilization/ Intracytoplasmic Sperm Injection (IVF/ICSI) cycle in women without
      polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: There is a low probability of
      the freeze-only strategy being cost-effective over the fresh ET strategy for non
      PCOS women undergoing IVF/ICSI. WHAT IS KNOWN ALREADY: Conventionally, IVF
      embryos are transferred in the same cycle in which oocytes are collected, while
      any remaining embryos are frozen and stored. We recently evaluated the
      effectiveness of a freeze-only strategy compared with a fresh ET strategy in a
      randomized controlled trial (RCT). There was no difference in live birth rate
      between the two strategies. STUDY DESIGN, SIZE, DURATION: A cost-effectiveness
      analysis (CEA) was performed alongside the RCT to compare a freeze-only strategy
      with a fresh ET strategy in non-PCOS women undergoing IVF/ICSI. The effectiveness
      measure for the CEA was the live birth rate. Data on the IVF procedure, pregnancy
      outcomes and complications were collected from chart review; additional
      information was obtained using patient questionnaires, by telephone.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: For all patients, we measured the
      direct medical costs relating to treatment (cryopreservation, pregnancy follow
      up, delivery), direct non-medical costs (travel, accommodation) and indirect
      costs (income lost). The direct cost data were calculated from resources obtained
      from patient records and prices were applied based on a micro-costing approach.
      Indirect costs were calculated based on responses to the questionnaire. Patients
      were followed until all embryos obtained from a single controlled ovarian
      hyperstimulation cycle were used or a live birth was achieved. The incremental
      cost-effectiveness ratio (ICER) was based on the incremental cost per couple and
      the incremental live birth rate of the freeze-only strategy compared with the
      fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost
      effectiveness acceptability curve (CEAC) were also performed. MAIN RESULTS AND
      THE ROLE OF CHANCE: Between June 2015 and April 2016, 782 couples were randomized
      to a freeze-only (n = 391) or a fresh ET strategy (n = 391). Baseline
      characteristics including mean age, Body Mass Index (BMI), anti-Mullerian
      hormone, total dose of Follicle Stimulating Hormone (FSH), number of oocytes
      obtained, good quality Day 3 embryos, fertility outcomes and treatment
      complications were comparable between the two groups. The live birth rate (48.6%
      vs. 47.3%, respectively; risk ratio, 1.03; 95% Confidence Interval [CI], 0.89,
      1.19; P = 0.78) and the average cost per couple (3906 vs. 3512 EUR, respectively;
      absolute difference 393.6, 95% CI, -76.2, 863.5; P = 0.1) were similar in the
      freeze-only group versus fresh ET. Corresponding costs per live birth were 8037
      EUR versus 7425 EUR in the freeze-only versus fresh ET group, respectively. The
      incremental cost for the freeze-only strategy compared with fresh ET was 30 997
      EUR per 1% additional live birth rate. The direct non-medical costs and indirect
      costs of infertility treatment strategies represented ~45-52% of the total cost.
      PSA shows that the 95% CI of ICERs was -263 901 to 286 681 EUR. Out of 1000
      simulations, 44% resulted in negative ICERs, including 13.0% of simulations in
      which the freeze-only strategy was dominant (more effective and less costly than
      fresh ET), and 31% of simulations in which the fresh embryo strategy was
      dominant. In the other 560 simulations with positive ICERs, the 95% CI of ICERs
      ranged from 2155 to 471 578 EUR. The CEAC shows that at a willingness to pay
      threshold of 300 000 EUR, the probability of the freeze-only strategy being cost
      effective over the fresh ET strategy would be 58%. LIMITATIONS, REASONS FOR
      CAUTION: Data were collected from a single private IVF center study in Vietnam
      where there is no public or insurance funding of IVF. Unit costs obtained might
      not be representative of other settings. Data obtained from secondary sources
      (medical records, financial and activity reports) could lack authenticity, and
      recall bias may have influenced questionnaire responses on which direct costs
      were based. WIDER IMPLICATIONS OF THE FINDINGS: In non-PCOS women undergoing
      IVF/ICSI, the results suggested that the freeze-only strategy was not cost
      effective compared with fresh ET from a patient perspective. These findings
      indicate that other factors could be more important in deciding whether to use a
      freeze-only versus fresh ET strategy in this patient group. STUDY
      FUNDING/COMPETING INTEREST(S): This study was funded by My Duc Hospital; no
      external funding was received. Ben Willem J. Mol is supported by an NHMRC
      Practioner Fellowship (GNT 1082548) and reports consultancy for Merck, ObsEva and
      Guerbet. Robert J. Norman has shares in an IVF company and has received support
      from Merck and Ferring. All other authors have no conflicts of interest to
      declare. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 30239785
TI  - Homozygous in-frame deletion in CATSPERE in a man producing spermatozoa with loss
      of CatSper function and compromised fertilizing capacity.
AB  - STUDY QUESTION: Does a man (patient 1) with a previously described deficiency in
      principle cation channel of sperm (CatSper) function have a mutation in the
      CatSper-epsilon (CATSPERE) and/or CatSper-zeta (CATSPERZ) gene? SUMMARY ANSWER:
      Patient 1 has a homozygous in-frame 6-bp deletion in exon 18
      (c.2393_2398delCTATGG, rs761237686) of CATSPERE. WHAT IS KNOWN ALREADY: CatSper
      is the principal calcium channel of mammalian spermatozoa. Spermatozoa from
      patient 1 had a specific loss of CatSper function and were unable to fertilize at
      IVF. Loss of CatSper function could not be attributed to genetic abnormalities in
      coding regions of seven CatSper subunits. Two additional subunits (CatSper
      epsilon (CATPSERE) and CatSper-zeta (CATSPERZ)) were recently identified, and are
      now proposed to contribute to the formation of the mature channel complex. STUDY
      DESIGN, SIZE, DURATION: This was a basic medical research study analysing genomic
      data from a single patient (patient 1) for defects in CATSPERE and CATSPERZ.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The original exome sequencing data for
      patient 1 were analysed for mutations in CATSPERE and CATSPERZ. Sanger sequencing
      was conducted to confirm the presence of a rare variant. MAIN RESULTS AND THE
      ROLE OF CHANCE: Patient 1 is homozygous for an in-frame 6-bp deletion in exon 18
      (c.2393_2398delCTATGG, rs761237686) of CATSPERE that is predicted to be highly
      deleterious. LIMITATIONS, REASONS FOR CAUTION: The nature of the molecular
      deficit caused by the rs761237686 variant and whether it is exclusively
      responsible for the loss of CatSper function remain to be elucidated. WIDER
      IMPLICATIONS OF THE FINDINGS: Population genetics are available for a significant
      number of predicted deleterious variants of CatSper subunits. The consequence of
      homozygous and compound heterozygous forms on sperm fertilization potential could
      be significant. Selective targeting of CatSper subunit expression maybe a
      feasible strategy for the development of novel contraceptives. STUDY
      FUNDING/COMPETING INTEREST(S): This study was funded by project grants from the
      MRC (MR/K013343/1 and MR/012492/1), Chief Scientist Office/NHS research Scotland.
      This work was also supported by NIH R01GM111802, Pew Biomedical Scholars Award
      00028642 and Packer Wentz Endowment Will to P.V.L. C.L.R.B is the editor-in-chief
      of Molecular Human Reproduction, has received lecturing fees from Merck and
      Ferring, and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B
      was chair of the World Health Organization Expert Synthesis Group on Diagnosis of
      Male infertility (2012-2016).

PMID- 30239788
TI  - More than 1200 embryo transfers with an endometrial thickness below 7 mm.

PMID- 30239787
TI  - Please, decline our invitation-again.

PMID- 30239786
TI  - Low-molecular weight compounds in human seminal plasma as potential biomarkers of
      male infertility.
AB  - STUDY QUESTION: Is the determination of antioxidants, oxidative/nitrosative
      stress-related compounds, purines, pyrimidines and energy-related metabolites in
      human seminal plasma of utility to evidence biomarkers related to male
      infertility? SUMMARY ANSWER: The determination of 26 metabolites in seminal
      plasma allowed to evidence that 21/26 of them are biomarkers of male infertility,
      as well as to calculate a cumulative index, named Biomarker Score, that fully
      discriminates fertile controls from infertile patients and partially
      differentiates infertile without from infertile with spermiogram anomalies. WHAT
      IS KNOWN ALREADY: Epidemiological studies indicated that a male factor is
      involved in ~50% of cases of pregnancy failure, with a significant percentage of
      infertile males having no alterations in the spermiogram. Further laboratory
      analyses of male infertility are mainly dedicated only to gross evaluations of
      oxidative stress or total antioxidant capacity. STUDY DESIGN, SIZE, DURATION:
      Seminal plasma of 48 fertile controls and 96 infertile patients (master group),
      were collected from September 2016 to February 2018. A second group of 44
      infertile patients (validation group) was recruited in a second, independent
      centre from September 2017 to March 2018. Samples were analysed in blind using a
      'Redox Energy Test' to determine various low-molecular weight compounds, with the
      aim of finding metabolic profiles and biomarkers related to male infertility.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: In all seminal plasma, 26 water- and
      fat-soluble compounds (related to antioxidant defences, oxidative/nitrosative
      stress, purine, pyrimidine and energy metabolism) were analysed using high
      performance liquid chromatographic methods. According to spermiogram, infertile
      patients of both groups were also categorized into normozoospermic (N, no
      anomalies in the spermiogram), or into the subgroup including all patients with
      anomalies in the spermiogram (asthenoteratooligozoospermic ATO +
      asthenozoospermic A + teratozoospermic T + oligozoospermic O). MAIN RESULTS AND
      THE ROLE OF CHANCE: In the master group, results indicated that 21/26 compounds
      assayed in seminal plasma of infertile males were significantly different from
      corresponding values determined in fertile controls. These 21 compounds
      constituted the male infertility biomarkers. Similar results were recorded in
      patients of the validation group. Using an index cumulating the biochemical
      seminal plasma anomalies (Biomarker Score), we found that fertile controls had
      mean Biomarker Score values of 2.01 +/- 1.42, whilst infertile patients of the
      master and of the validation group had mean values of 12.27 +/- 3.15 and of 11.41
      +/- 4.09, respectively (P < 0.001 compared to controls). The lack of statistical
      differences between the master and the validation groups, in both the metabolic
      profiles and the Biomarker Score values, allowed to pool patients into a single
      cohort of infertile males. The Biomarker Score values showed that fertile
      controls and infertile males clustered into two distinct groups. Infertile
      patients without (N, n = 42) or with (ATO + A + T + O, n = 98) spermiogram
      anomalies differed in some biomarkers (ascorbic acid, all-trans retinol, alpha
      tocopherol, cytidine, uridine, guanine). These differences were reinforced by
      distribution frequencies and posterior probability curves of the Biomarker Score
      in the three groups. LIMITATIONS, REASONS FOR CAUTION: Results were obtained in
      relatively limited number of human seminal plasma samples. Using the 'Redox
      Energy Test' it was possible to associate specific metabolic profiles and values
      of the Biomarker Score to fertile controls or infertile males. However, it was
      not possible to evaluate whether the different anomalies of the spermiogram are
      associated with specific metabolic profiles and values of the Biomarker Score.
      WIDER IMPLICATIONS OF THE FINDINGS: The 'Redox Energy Test', coupled with the
      Biomarker Score that cumulates the biochemical characteristics of seminal plasma
      into a single index, evidenced a set of low-molecular weight biomarkers
      potentially useful in the laboratory management of male infertility. STUDY
      FUNDING/COMPETING INTEREST(S): The study was partly funded with research grants
      from the University of Catania. None of the authors have any conflicting
      interests to declare.

PMID- 30239789
TI  - Canonical NF-kappaB signaling regulates satellite stem cell homeostasis and
      function during regenerative myogenesis.
AB  - Skeletal muscle regeneration in adults is attributed to the presence of satellite
      stem cells that proliferate, differentiate, and eventually fuse with injured
      myofibers. However, the signaling mechanisms that regulate satellite cell
      homeostasis and function remain less understood. While IKKbeta-mediated canonical
      NF-kappaB signaling has been implicated in the regulation of myogenesis and
      skeletal muscle mass, its regulation of satellite cell function during muscle
      regeneration remains less understood. Here, we report that canonical NF-kappaB
      signaling is induced in skeletal muscle upon injury. Satellite cell-specific
      inducible ablation of IKKbeta attenuates skeletal muscle regeneration in adult
      mice. Targeted ablation of IKKbeta also reduces the number of satellite cells in
      injured skeletal muscle of adult mice, potentially through inhibiting their
      proliferation and survival. We also demonstrate that the inhibition of components
      of the canonical NF-kappaB pathway causes precocious differentiation of cultured
      satellite cells both ex vivo and in vitro. Finally, our results highlight that
      the constitutive activation of canonical NF-kappaB signaling in satellite cells
      also attenuates skeletal muscle regeneration following injury in adult mice.
      Collectively, our study demonstrates that the proper regulation of canonical NF
      kappaB signaling is important for the regeneration of adult skeletal muscle.

PMID- 30239790
TI  - Argemone mexicana (Papaverales: Papavaraceae) as an Alternative for Mosquito
      Control: First Report of Larvicidal Activity of Flower Extract.
AB  - Culex quinquefasciatus Say (Diptera: Culicidae), an arboviral and filarial
      vector, is one of the most widespread mosquitoes in the world. The indiscriminate
      use of synthetic chemical insecticides has led to the development of resistance
      in mosquito populations worldwide. The effect of continuous exposure to crude
      extracts of Argemone mexicana, the Mexican poppy, on the development and growth
      stages of second-instar larvae of the mosquito was studied, along with
      qualitative chemical analysis of the different plant parts. Inhibition,
      mortality, and larval and pupal duration phases were assessed. Second-instar
      mosquito larvae were exposed to crude ethanol extracts of flowers, stems, and
      seeds. Flower extract exhibited the strongest larvicidal activity with LC50 and
      LC90 values after 24 h of exposure of 18.61 and 39.86 ppm, respectively, and 9.47
      and 21.76 ppm after 48 h. Extracts from stem and seeds were significantly less
      effective. The flower extract registered a Growth Inhibition Index of 0.01 at 25
      ppm, with stems and seeds registering 0.05 and 0.08, respectively, at 100 ppm
      (control group 1.02). Qualitative chemical analysis by thin-layer chromatography
      showed characteristic spots indicating the presence of alkaloids and flavonoids
      and phytochemical screening showed the presence of alkaloids, anthraquinones,
      flavonoids, tannins, and terpenoids in the various crude extracts. This is the
      first report of the effectiveness of an ethanol flower extract of A. mexicana on
      Cx. quinquefasciatus; it can be considered a promising alternative control for
      this mosquito species.

PMID- 30239792
TI  - Adrenal Vein Sampling Lateralization Despite Mineralocorticoid Receptor
      Antagonists Exposure in Primary Aldosteronism.
AB  - Context: Many antihypertensive medications modulate the renin-angiotensin
      aldosterone system, possibly skewing the diagnosis and subtyping of primary
      aldosteronism (PA). Particularly, mineralocorticoid receptor antagonists (MRA)
      might raise renin and stimulate aldosterone synthesis from non-autonomous areas,
      potentially obscuring lateralization on adrenal vein sampling (AVS). Withdrawal
      of MRA in severe PA, however, can precipitate hypokalemia and/or hypertension and
      therefore is not always practical. Objective: To assess the effects of MRA on the
      interpretation of AVS data. Design and Participants: A cohort study of all PA
      patients who underwent AVS at University of Michigan between January, 2009 and
      January, 2018 was conducted. Demographics, diagnostic, AVS, surgical pathology
      and follow up data were collected retrospectively. Results: Of 191 patients who
      underwent AVS, 51 (27%) were exposed to MRA at the time of the procedure. Plasma
      aldosterone concentration and the daily defined dose of antihypertensives were
      higher in patients taking vs. those not taking MRA. Unilateral PA was more
      frequent in the MRA group, both pre- and post-cosyntropin (p < 0.05). The MRA
      group included two patients with unsuppressed renin, who demonstrated unequivocal
      AVS lateralization. To date, 86 patients underwent unilateral adrenalectomy,
      including 30 patients taking MRA during AVS. The proportion of clinical and
      biochemical success was not statistically different between patients exposed to
      and those not exposed to MRA during AVS (p= 0.17 and 0.65, respectively).
      Conclusion: Our data suggest that conclusive AVS lateralization is often achieved
      in patients with severe PA despite MRA use.

PMID- 30239793
TI  - Smoking Rates and Number of Cigarettes Smoked per Day in Schizophrenia: A Large
      Cohort Meta-Analysis in a Japanese Population.
AB  - Background: Cigarette smoking is consistently more common among schizophrenia
      patients than the general population worldwide; however, the findings of studies
      in Japan are inconsistent. Recently, the smoking rate has gradually decreased
      among the general population. Methods: We performed a meta-analysis of smoking
      status in a large Japanese cohort of (1) 1845 schizophrenia patients and 196845
      general population and (2) 842 schizophrenia patients and 766 psychiatrically
      healthy controls from 12 studies over a 25-year period, including 301 patients
      and 131 controls from our study. Results: In our case-control sample,
      schizophrenia patients had a significantly higher smoking rate than healthy
      controls (P=.031). The proportion of heavy smokers (P=.027) and the number of
      cigarettes smoked per day (P=8.20*10-3) were significantly higher among
      schizophrenia patients than healthy controls. For the smokers in the
      schizophrenia group, atypical antipsychotics dosage was positively correlated
      with cigarettes per day (P=1.00*10-3). A meta-analysis found that schizophrenia
      patients had a higher smoking rate than the general population for both men
      (OR=1.53, P=.035; schizophrenia patients, 52.9%; general population, 40.1%) and
      women (OR=2.40, P=1.08*10-5; schizophrenia patients, 24.4%; general population,
      11.8%). In addition, male schizophrenia patients had a higher smoking rate than
      male healthy controls (OR=2.84, P=9.48*10-3; schizophrenia patients, 53.6%;
      healthy controls, 32.9%), but the difference was not significant for women
      (OR=1.36, P=.53; schizophrenia patients, 17.0%; healthy controls,14.1%). Among
      both males and females, schizophrenia patients had a higher smoking rate than
      both the general population (OR=1.88, P=2.60*10-5) and healthy controls (OR=2.05,
      P=.018). These rates were not affected by the patients' recruitment year (P>.05).
      The cigarettes per day values of schizophrenia patients and the general
      population were 22.0 and 18.8, respectively. Conclusions: Schizophrenia patients
      are approximately 2 times more likely to smoke than the general population and
      healthy controls based on data collected over a decade in Japan.

PMID- 30239791
TI  - Mechanistic insights into histone deposition and nucleosome assembly by the
      chromatin assembly factor-1.
AB  - Eukaryotic chromatin is a highly dynamic structure with essential roles in
      virtually all DNA-dependent cellular processes. Nucleosomes are a barrier to DNA
      access, and during DNA replication, they are disassembled ahead of the
      replication machinery (the replisome) and reassembled following its passage. The
      Histone chaperone Chromatin Assembly Factor-1 (CAF-1) interacts with the
      replisome and deposits H3-H4 directly onto newly synthesized DNA. Therefore, CAF
      1 is important for the establishment and propagation of chromatin structure. The
      molecular mechanism by which CAF-1 mediates H3-H4 deposition has remained
      unclear. However, recent studies have revealed new insights into the architecture
      and stoichiometry of the trimeric CAF-1 complex and how it interacts with and
      deposits H3-H4 onto substrate DNA. The CAF-1 trimer binds to a single H3-H4
      dimer, which induces a conformational rearrangement in CAF-1 promoting its
      interaction with substrate DNA. Two CAF-1*H3-H4 complexes co-associate on
      nucleosome-free DNA depositing (H3-H4)2 tetramers in the first step of nucleosome
      assembly. Here, we review the progress made in our understanding of CAF-1
      structure, mechanism of action, and how CAF-1 contributes to chromatin dynamics
      during DNA replication.

PMID- 30239794
TI  - Effects of Radiotherapy in Early-Stage, Low-Recurrence Risk, Hormone-Sensitive
      Breast Cancer.
AB  - Background: Radiotherapy after breast conservation has become the standard of
      care. Prior meta-analyses on effects of radiotherapy predated availability of
      gene expression profiling (GEP) to assess recurrence risk and/or did not include
      all relevant outcomes. This analysis used GEP information with pooled individual
      level data to evaluate the impact of omitting radiotherapy on recurrence and
      mortality. Methods: We considered trials that evaluated or administered
      radiotherapy after lumpectomy in women with low-risk breast cancer. Women
      included had undergone lumpectomy and were treated with hormonal therapy for
      stage I, ER+ and/or PR+, HER2- breast cancer with Oncotype scores no greater than
      18. Recurrence-free interval (RFI), type of RFI (locoregional or distant), and
      breast cancer-specific and overall survival were compared between no radiotherapy
      and radiotherapy using adjusted Cox models. All statistical tests were two-sided.
      Results: The final sample included 1778 women from seven trials. Omission of
      radiotherapy was associated with an overall adjusted hazard ratio of 2.59 (95%
      confidence interval [CI] = 1.38 to 4.89, P = .003) for RFI. There was a
      statistically significant increase in any first locoregional recurrence (P =
      .001), but not distant recurrence events (P = .90), or breast cancer-specific (P
      = .85) or overall survival (P = .61). Five-year RFI rate was high (93.5% for no
      radiotherapy vs 97.9% for radiotherapy; absolute reduction = 4.4%, 95% CI = 0.7%
      to 8.1%, P = .03). The effects of radiotherapy varied across subgroups, with
      lower RFI rates for those with Oncotype scores of less than 11 (vs 11-18), older
      (vs younger), and ER+/PR+ status (vs other). Conclusions: Omission of
      radiotherapy in hormone-sensitive patients with low recurrence risk may lead to a
      modest increase in locoregional recurrence event rates, but does not appear to
      increase the rate of distant recurrence or death.

PMID- 30239796
TI  - ProGeM: a framework for the prioritization of candidate causal genes at molecular
      quantitative trait loci.
AB  - Quantitative trait locus (QTL) mapping of molecular phenotypes such as
      metabolites, lipids and proteins through genome-wide association studies
      represents a powerful means of highlighting molecular mechanisms relevant to
      human diseases. However, a major challenge of this approach is to identify the
      causal gene(s) at the observed QTLs. Here, we present a framework for the
      'Prioritization of candidate causal Genes at Molecular QTLs' (ProGeM), which
      incorporates biological domain-specific annotation data alongside genome
      annotation data from multiple repositories. We assessed the performance of ProGeM
      using a reference set of 227 previously reported and extensively curated
      metabolite QTLs. For 98% of these loci, the expert-curated gene was one of the
      candidate causal genes prioritized by ProGeM. Benchmarking analyses revealed that
      69% of the causal candidates were nearest to the sentinel variant at the
      investigated molecular QTLs, indicating that genomic proximity is the most
      reliable indicator of 'true positive' causal genes. In contrast, cis-gene
      expression QTL data led to three false positive candidate causal gene assignments
      for every one true positive assignment. We provide evidence that these
      conclusions also apply to other molecular phenotypes, suggesting that ProGeM is a
      powerful and versatile tool for annotating molecular QTLs. ProGeM is freely
      available via GitHub.

PMID- 30239795
TI  - Structural insights into the mechanism of double strand break formation by
      Hermes, a hAT family eukaryotic DNA transposase.
AB  - Some DNA transposons relocate from one genomic location to another using a
      mechanism that involves generating double-strand breaks at their transposon ends
      by forming hairpins on flanking DNA. The same double-strand break mode is
      employed by the V(D)J recombinase at signal-end/coding-end junctions during the
      generation of antibody diversity. How flanking hairpins are formed during DNA
      transposition has remained elusive. Here, we describe several co-crystal
      structures of the Hermes transposase bound to DNA that mimics the reaction step
      immediately prior to hairpin formation. Our results reveal a large DNA
      conformational change between the initial cleavage step and subsequent hairpin
      formation that changes which strand is acted upon by a single active site. We
      observed that two factors affect the conformational change: the complement of
      divalent metal ions bound by the catalytically essential DDE residues, and the
      identity of the -2 flanking base pair. Our data also provides a mechanistic link
      between the efficiency of hairpin formation (an A:T basepair is favored at the -2
      position) and Hermes' strong target site preference. Furthermore, we have
      established that the histidine residue within a conserved C/DxxH motif present in
      many transposase families interacts directly with the scissile phosphate,
      suggesting a crucial role in catalysis.

PMID- 30239798
TI  - Comprehending practitioners' assessments of community-led total sanitation.
AB  - Around 2.3 billion people in developing countries still lack access to improved
      sanitation facilities and almost one billion practice open defecation (OD). The
      Community-Led Total Sanitation (CLTS) has recently become a particularly popular
      approach used in more than 60 countries. CLTS is a behavior-change approach that
      aims to ignite community action and make OD socially unacceptable without
      providing any external financial or material support to individual households.
      CLTS is sometimes perceived as a revolutionary approach that has proven to be
      highly cost-effective in abolishing OD. However, it has been criticized for its
      use of unethical practices and questioned with respect to the sustainability of
      its outcomes and the limited health benefits it can generate. Based on semi
      structured interviews with development workers experienced in the implementation
      of CLTS in 14 different countries, this paper seeks to examine practical views on
      the issues surrounding this approach. We found that despite acknowledging some of
      the controversies and the possibly limited sustainability of results, CLTS is
      generally considered an effective and satisfactory tool for improving sanitation
      conditions. Practitioners first of all accentuate the normative importance of the
      elimination of OD attained through CLTS without weighting on (the absence of)
      evidence on the longer term effects or impacts on health. However, a need for
      various modifications of CLTS according to local social and natural environments
      was strongly expressed, including changes that go against the core principles of
      CLTS like no subsidies and no technical assistance principles.

PMID- 30239797
TI  - The first Portuguese National Health Examination Survey (2015): design, planning
      and implementation.
AB  - Background: In Health Examination Surveys interview information is complemented
      with objective information, providing more accurate indicators than self-reported
      data. We report the study design, planning and implementation of the first
      Portuguese Health Examination Survey (INSEF). Methods: INSEF was a cross
      sectional population-based study representative at regional and national level.
      Individuals aged between 25 and 74 years old, residing in Portugal were selected
      from the national health users' registry through multi-stage stratified
      probabilistic sampling. Sample size was set at 4200 individuals. Data was
      collected in primary care units and included blood pressure, height, weight, hip
      and waist measurements, blood collection for lipid profile, HbA1c and blood count
      and a general health questionnaire. European HES procedures were followed.
      Results: A total of 4911 individuals agreed to participate (43.9% participation
      rate). Participation rate varied by region, sex and age group, being lower in
      Lisbon and Tagus Valley (32.8%), for men (41.8%) and for those aged 25-34 years
      old (36%). Conclusions: INSEF has set up an experienced national and regional
      structure for HES implementation. Nationally representative quality
      epidemiological data is now available for public health monitoring, planning and
      research.

PMID- 30239799
TI  - Safety of Anti-TNF-Alpha Therapy During Pregnancy on Long-term Outcome of Exposed
      Children: A Controlled, Multicenter Observation.
AB  - Background: Evidence of the impact of in utero exposure to anti-tumor necrosis
      factor (TNF)-alpha on long-term childhood development is limited. The aim was to
      assess the impact of in utero exposure to anti-TNF-alpha due to mothers'
      inflammatory bowel disease (IBD) on long-term postnatal development of exposed
      children. Methods: We included consecutive children (>=12 months of age) born to
      mothers with IBD (2007-2016) treated with anti-TNF-alpha during pregnancy in 3
      centers in the Czech Republic. A control group was comprised of unexposed
      children of non-IBD mothers undergoing mandatory check-ups at general
      pediatricians' offices. Data on perinatal period, psychomotor development,
      vaccination, infections, antibiotics, and allergy were collected by treating
      pediatricians using a predefined questionnaire. Results: Seventy-two exposed and
      69 unexposed children were included (median age, 35 and 50 months, respectively).
      Exposed children had growth and psychomotor development similar to controls.
      There was no significant difference in infectious complications within the first
      year of life (23.9% vs 17.4%; P = 0.36) or during the whole follow-up between
      exposed infants and controls (P = 0.32). Concomitant immunosuppressants during
      pregnancy and anti-TNF-alpha levels in cord blood were not associated with
      elevated infection rate within the first year of life (P > 0.05). Over 95% of
      exposed children had adequate serologic response to vaccination, except for
      haemophilus and mumps vaccines. Clinically manifested allergy was similar between
      the groups (P = 0.98). Conclusions: Anti-TNF-alpha exposure in utero does not
      seem to have a negative impact on postnatal development of children with regard
      to infectious complications, allergy, growth, or psychomotor development when
      compared with unexposed children of non-IBD women.

PMID- 30239800
TI  - Pathological Relationship Between Adamantinomatous Craniopharyngioma and Adjacent
      Structures Based on QST Classification.
AB  - The aim of this study was to clarify pathological and anatomical relationships
      between adamantinomatous craniopharyngiomas (ACP) and their surrounding
      structures. We previously established a QST classification scheme based on the
      apparent anatomic origin of the tumors. According to this classification, 13 type
      Q tumors, 6 type S tumors, and 42 type T ACPs were analyzed. Type Q tumors, which
      are most likely to involve the pituitary gland, did not invade the area of
      contact with the adenohypophysis. Instead, tumor invasion was observed in areas
      where the tumor contacted the neurohypophysis. Type S tumors primarily involved
      the pituitary stalk; the arachnoid remained present between these tumors and
      normal structures. Type T tumors were located beneath the basal arachnoid
      membrane and outside the pia mater. The pia mater was disrupted and finger-like
      invasions were found in the neural layer of the third ventricle floor along the
      invasive front. Tumors were never observed to break through the ependymal layer
      of the third ventricle. The QST classification has important implications for
      understanding the growth pattern of tumors and can be used to guide surgical
      procedures.

PMID- 30239802
TI  - The Health Threat Posed by the Hidden Epidemic of Anabolic Steroid Use and Body
      Image Disorders Among Young Men.
AB  - Context: The prevalence of body image disorders and anabolic-androgenic steroid
      (AAS) use is increasing, despite the evidence of their serious adverse health
      effects and despite the passage of laws regulating their sales. Here we review
      the evolution of the dual emerging epidemics of body image disorders and AAS use,
      adverse health effects of AAS, and the need for an integrated health policy and
      regulatory response to stem these epidemics. Evidence Acquisition: We searched
      for studies published in English language prior to June 2018. Quality of evidence
      was low to moderate because of its observational nature; heterogeneity of
      eligibility criteria; variable doses; reliance on retrospective self-reported
      data in many studies; and variable quality of outcome ascertainment. Evidence
      Synthesis: Most AAS users are nonathlete young men, who use these substances to
      look lean and more muscular. Some of these men suffer from "muscle dysmorphia," a
      form of body dysmorphic disorder characterized by pathological preoccupation with
      muscularity. AAS has been associated with cardiovascular disorders
      (cardiomyopathy and accelerated coronary artery disease), psychiatric disorders
      (mania, hypomania, depression and suicidality), AAS-withdrawal hypogonadism,
      infertility, neurotoxic effects, musculoskeletal injuries, liver toxicity, and
      needle-borne infections. Potential adverse effects may be compounded by the use
      of other substances (e.g., opioids) and high-risk behaviors. Unregulated internet
      sales of AAS and selective androgen receptor modulators, which are easily
      purchased without a prescription is of great concern because of its potential to
      fuel the epidemic among adolescents and the military. Conclusions: Integrated
      nationwide efforts are necessary to raise public awareness of this epidemic, to
      study long-term health effects of AAS and treatment strategies, and to reform
      regulations to stem the epidemics of AAS use and body image disorders.

PMID- 30239801
TI  - Maternal Iodine Insufficiency and Excess Are Associated with Adverse Effects on
      Fetal Growth: A Prospective Cohort Study in Wuhan, China.
AB  - Background: Maternal iodine status has been suggested to affect birth outcomes.
      Few studies have focused on its effects on fetal growth during pregnancy.
      Objective: This study aimed to assess maternal iodine status during early
      pregnancy and further examine the relation between maternal iodine status and
      fetal growth. Methods: A total of 2087 singleton-pregnant women participating in
      the Tongji Maternal and Child Health Cohort study were involved. Urinary iodine
      concentration (UIC) and creatinine concentration were measured in spot urine
      samples collected in early pregnancy (<20 wk of gestation). Fetal head
      circumference (HC), femur length (FL), and estimated fetal weight (EFW) were
      evaluated by ultrasonography in each trimester. A multiple linear regression
      model was used to examine the association of iodine status with fetal growth
      characteristics, and a mixed-effects model was used to assess longitudinal
      effect. Results: The median UIC and iodine-to-creatinine (I/Cr) ratio were 178
      MUg/L and 234 MUg/g, respectively. The prevalence of insufficient iodine status
      (I/Cr ratio <150 MUg/g) was 19.8%(n = 414), of adequate iodine status (150-249
      MUg/g) was 34.8% (n = 726), of iodine status above the requirements (250-499
      MUg/g) was 32.1% (n = 669), and of excessive iodine status (>=500 MUg/g) was
      13.3% (n = 278). Maternal iodine insufficiency was inversely associated with
      fetal FL in the second and third trimesters. In stratified analysis, significant
      interactions were found between maternal iodine status and age as well as parity
      (all P < 0.05). The longitudinal analyses showed negative associations of
      maternal insufficient, more than adequate, or excessive iodine status with fetal
      growth during pregnancy (all P < 0.05). Conclusions: In central China, maternal
      iodine insufficiency and excess coexisted during early pregnancy and they both
      adversely affected fetal growth. There is an urgent need for ongoing monitoring
      of iodine status among vulnerable pregnant women in order to optimize iodine
      nutrition during pregnancy.

PMID- 30239803
TI  - Clinical, Biochemical and Genetic Characteristics of "Non-Classical" Apparent
      Mineralocorticoid Excess Syndrome.
AB  - Context: Classical apparent mineralocorticoid excess (AME) is a rare recessive
      disorder, caused by 11beta-HSD2 deficiency. AME manifests as low-renin pediatric
      hypertension, hypokalemia and high cortisol/cortisone (F/E) ratio. Objective: To
      evaluate "Non-classical" AME (NC-AME) due to partial 11beta-HSD2 insufficiency
      and its association with hypertension, mineralocorticoid receptor (MR) activation
      and inflammatory parameters. Design: Cross-sectional study. Setting: Primary care
      cohort. Participants: We recruited 127 adolescents and adults. Subjects with
      secondary hypertension were excluded. We measured clinical, biochemical, renal,
      vascular and inflammatory variables. Sequencing of HSD11B2 gene was performed in
      all subjects. Main Outcome Measure: Non-classical AME. Results: Serum F/E ratio
      was positively associated with systolic Blood Pressure (SBP), microalbuminuria
      and hs-CRP. Serum cortisone correlated with MR-activation parameters even when
      adjusted for age, BMI and sex: lower cortisone with higher potassium excretion
      (partial r= -0.29, p=0.002) and with lower plasma renin activity (PRA, partial r=
      0.29, p=0.001). Consistently, we identified, 9/127 subjects (7.1%) with high F/E
      ratio (First quartile) and low cortisone (Last quartile), suggestive of NC-AME.
      These subjects had higher SBP (mmHg): 141.4 +/- 25.7 vs 127.3 +/- 18.1 p=0.03;
      lower PRA (ng/L*s): 0.36 +/- 0.19 vs 0.64 +/- 0.47, p<0.0001) and greater
      potassium excretion, microalbuminuria, hs-CRP and PAI-1. We only found in 2/9 NC
      AME subjects heterozygous mutations in HSD11B2 gene. Conclusions: These findings
      suggest a spectrum of partial 11beta-HSD2 insufficiency in a Primary care cohort
      without the classical phenotype/genotype of AME. "Non-classical" AME may
      represent a phenotype of MR-activation and cardiovascular risk suggesting that
      these subjects could be targeted with MR antagonists.

PMID- 30239804
TI  - Pathophysiological aspects of Aspergillus colonization in disease.
AB  - Aspergillus colonization of the lower respiratory airways is common in normal
      people, and of little clinical significance. However, in some patients,
      colonization is associated with severe disease including poorly controlled
      asthma, allergic bronchopulmonary aspergillosis (ABPA) with sputum plugs, worse
      lung function in chronic obstructive pulmonary aspergillosis (COPD), invasive
      aspergillosis, and active infection in patients with chronic pulmonary
      aspergillosis (CPA). Therefore, understanding the pathophysiological mechanisms
      of fungal colonization in disease is essential to develop strategies to avert or
      minimise disease. Aspergillus cell components promoting fungal adherence to the
      host surface, extracellular matrix, or basal lamina are indispensable for
      pathogen persistence. However, our understanding of individual differences in
      clearance of A. fumigatus from the lung in susceptible patients is close to zero.

PMID- 30239805
TI  - Mullerian-Inhibiting Substance/Anti-Mullerian Hormone as a Predictor of Preterm
      Birth in Polycystic Ovary Syndrome.
AB  - Context: There is increasing evidence for Mullerian-inhibiting substance
      (MIS)/anti-Mullerian hormone (AMH) physiologic activity in the human uterus, so
      it is relevant to study how MIS/AMH levels impact pregnancy. Objective: To
      investigate the association of MIS/AMH levels with the risk of adverse obstetric
      outcomes. Design: Retrospective cohort study. Setting: Academic fertility center.
      Patients: Women who became pregnant through in vitro fertilization between
      January 2012 and October 2016. Exclusion criteria were: oocyte donation,
      gestational carrier, multiple gestations, miscarriage before 20 weeks, or
      medically indicated preterm deliveries. Interventions: None. Main Outcome
      Measures: There were two primary outcomes, preterm birth and cesarean delivery
      for arrest of labor. Because MIS/AMH level is highly skewed by certain
      infertility diagnoses, the preterm birth analysis was stratified by polycystic
      ovary syndrome (PCOS) diagnosis, and the cesarean delivery for arrest of labor
      analysis was stratified by diminished ovarian reserve diagnosis. chi2, Mann
      Whitney, and t tests were used as appropriate. A P value of <0.05 was considered
      statistically significant. Results: Among women with PCOS, those who delivered
      prematurely had substantially higher MIS/AMH levels (18 vs 6.4 ng/mL, P = 0.003)
      than did those who delivered at term. At the highest MIS/AMH values, preterm
      deliveries predominated; above the 90th percentile in women with PCOS, all
      deliveries were premature. No effect of MIS/AMH level was observed in women
      without PCOS. We found no association between MIS/AMH values and cesarean
      delivery for labor arrest. Conclusion: In women with PCOS, substantially elevated
      MIS/AMH levels are significantly associated with preterm birth, suggesting closer
      follow-up and further studies to elucidate the underlying mechanisms.

PMID- 30239806
TI  - The SAUR gene family: the plant's toolbox for adaptation of growth and
      development.
AB  - The family of Small Auxin Up-Regulated genes (SAURs) is a family of auxin
      responsive genes with about 60 to 140 members in most higher plant species.
      Despite the early discovery of their auxin responsiveness, their function and
      mode of action remained unknown for a long time. In recent years, the importance
      of SAUR genes for the regulation of dynamic and adaptive growth, and the
      molecular mechanisms by which SAUR proteins act are increasingly understood.
      SAURs play a central role in auxin-induced acid growth, but can also act
      independently of auxin, tissue-specifically regulated by various other hormone
      pathways and transcription factors. In this review, we summarize the recent
      advances in SAUR gene characterization in Arabidopsis and other plant species. We
      particularly elaborate on their capacity to fine tune growth in response to
      internal and external signals, and discuss the breakthroughs in understanding the
      mode of action of the SAURs in relation to their complex regulation.

PMID- 30239807
TI  - CBL-interacting protein kinase 25 contributes to root meristem development.
AB  - Coordination of auxin and cytokinin activities determines root meristem size
      during post-embryonic development. Calcineurin B-like proteins (CBLs) and their
      interacting protein kinases (CIPKs) constitute signaling modules that relay
      calcium signals. Here we report that CIPK25 is involved in regulating the root
      meristem size. Arabidopsis plants lacking CIPK25 expression displayed a short
      root phenotype and a slower root growth rate with less meristem cells. This
      phenotype was rescued by restoration of CIPK25 expression. CIPK25 interacted with
      CBL4 and -5, and displayed a strong gene expression in the flower and root except
      in the cell proliferation domain in the root apical meristem. Its expression in
      root was positively and negatively regulated by auxin and cytokinin,
      respectively. cipk25 T-DNA insertion line was compromised in auxin transport and
      auxin-responsive promoter activity. cipk25 mutant line showed altered expression
      of auxin efflux carriers and an Aux/IAA family gene SHY2. Decreased PIN1 and PIN2
      expression in cipk25 mutant line was completely restored when combined with SHY2
      loss-of-function mutation resulting in recovery of root growth. SHY2 and PIN1
      expression was partially regulated by cytokinin even in absence of CIPK25,
      suggesting existence of CIPK25-independent cytokinin signaling pathway(s) as
      well. Our results suggested a role of CIPK25 in root meristem development.

PMID- 30239808
TI  - Mobilizing an underused resource: cohort studies for population health
      intervention research.

PMID- 30239809
TI  - Time trends and geographical variation in prescribing of antibiotics in England
      1998-2017.
AB  - Background: Reducing antibiotic overuse is a key NHS priority. The majority of
      antibiotics are prescribed in primary care. Objectives: To describe antibiotic
      prescribing trends in NHS England primary care for the years 1998-2017 using
      various measures. We investigated trends and variation between practices and
      geographical areas, out-of-hours prescribing, and seasonality. Methods: We used
      publicly available prescribing datasets and calculated antibiotic prescribing
      rates per 1000 age-sex-adjusted population units, percentage prescribed as broad
      spectrum, and course length. We report national time trends for 1998-2016,
      geographical variation across 2017 and variation trends for 2010-17. We
      calculated percentiles and ranges, and plotted maps. Results: The overall rate of
      antibiotic prescribing has reduced by 18% since 2010, with the steepest decline
      since 2013. The percentage prescribed as broad-spectrum declined since 2006, from
      18.0 to 8.4. Between the best and worst Clinical Commissioning Groups (CCGs)
      there was 2-fold variation for total antibiotic prescribing, but 7-fold variation
      for cephalosporins. Variation across general practices has declined. The CCG to
      which a practice belongs accounted for 12.6% of current variation (P < 0.0001).
      Higher antibiotic prescribing was associated with greater practice size,
      proportion of patients >65 years or <18 years, ruralness and deprivation.
      Seasonal increases have been declining for most antibiotics. If every practice
      prescribed antibiotics at the lowest decile rate in 2017, 10.8 million fewer
      prescriptions could have been issued (34%). Compared with standard practices, out
      of-hours practices prescribed a greater proportion of broad-spectrum antibiotics.
      Conclusions: Despite a general trend towards more optimal antibiotic prescribing,
      considerable geographical variation persists across England's practices and CCGs.

PMID- 30239810
TI  - Efficacy and unintended consequences of hard-stop alerts in electronic health
      record systems: a systematic review.
AB  - Objective: Clinical decision support (CDS) hard-stop alerts-those in which the
      user is either prevented from taking an action altogether or allowed to proceed
      only with the external override of a third party-are increasingly common but can
      be problematic. To understand their appropriate application, we asked 3 key
      questions: (1) To what extent are hard-stop alerts effective in improving patient
      health and healthcare delivery outcomes? (2) What are the adverse events and
      unintended consequences of hard-stop alerts? (3) How do hard-stop alerts compare
      to soft-stop alerts? Methods and Materials: Studies evaluating computerized hard
      stop alerts in healthcare settings were identified from biomedical and computer
      science databases, gray literature sites, reference lists, and reviews. Articles
      were extracted for process outcomes, health outcomes, unintended consequences,
      user experience, and technical details. Results: Of 32 studies, 15 evaluated
      health outcomes, 16 process outcomes only, 10 user experience, and 4 compared
      hard and soft stops. Seventy-nine percent showed improvement in health outcomes
      and 88% in process outcomes. Studies reporting good user experience cited heavy
      user involvement and iterative design. Eleven studies reported on unintended
      consequences including avoidance of hard-stopped workflow, increased alert
      frequency, and delay to care. Hard stops were superior to soft stops in 3 of 4
      studies. Conclusions: Hard stops can be effective and powerful tools in the CDS
      armamentarium, but they must be implemented judiciously with continuous user
      feedback informing rapid, iterative design. Investigators must report on
      associated health outcomes and unintended consequences when implementing IT
      solutions to clinical problems.

PMID- 30239811
TI  - A Gas Chromatography-Mass Spectrometry Method for Toxicological Analysis of MDA,
      MDEA and MDMA in Vitreous Humor Samples from Victims of Car Accidents.
AB  - Vitreous humor (VH) shows excellent potential as a matrix of choice for
      postmortem analytical toxicology due to the ease of sampling and low metabolic
      activity. This study demonstrates a simple and rapid analytical method to
      identify and quantify 3,4-methylenedioxyamphetamine, 3,4
      methylenedioxymethamphetamine and 3,4-methylenedioxy-ethylamphetamine in VH.
      Samples were collected with a simple eye puncture procedure, followed by liquid
      liquid extraction and derivatization with heptafluorobutyric anhydride and
      analysis via gas chromatography-mass spectrometry. The accuracy of the method
      ranged 97-103%, intra-assay precision was between 4.54 and 9.14% relative
      standard deviation (RSD) and interassay precision ranged from 6.92 to 10.59% RSD.
      Limits of detection and quantification ranged from 1.0 to 2.5 ng/mL and 10 ng/mL,
      respectively. The validated method was successfully applied to detect
      methylenedioxyamphetamine derivatives in VH samples collected from victims of
      fatal car crashes.

PMID- 30239813
TI  - Prepartum fatty acid supplementation in sheep. III. Effect of eicosapentaenoic
      acid and docosahexaenoic acid during finishing on performance, hypothalamus gene
      expression, and muscle fatty acids composition in lambs.
AB  - The objectives of this study were to evaluate the effect of feeding an enriched
      diet with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to finishing
      lambs born from ewes supplemented either with or without EPA and DHA during late
      gestation on productive performance, muscle fatty acid (FA), and hypothalamus
      mRNA concentration of metabolic genes and hormone receptors. Lambs born from dams
      fed during the last 50 d of gestation either with a control diet containing 0.39%
      Ca salts of palmitic fatty acid distillate (C) or Ca salts enriched with EPA and
      DHA (PFA) were used. After weaning lambs (n = 70) were blocked by weight (BW) and
      used in a 2 * 2 factorial into 2 finishing diets containing 1.5% of C or PFA. The
      2 factors were the ewe diet and the finishing diet. Lambs (37.9 +/- 0.4 kg) were
      weighed and blood sampled for glucose and NEFA measurements at days 1, 14, 28,
      and 42. Dry matter intake (DMI) was measured daily. At day 43, 14 females and 14
      males were slaughtered, and hot carcass weight, body wall thickness, rib eye
      area, and FA composition of Longissumus thoracis muscle were evaluated. Female
      hypothalamuses were obtained and mRNA concentration of hormone receptors,
      neuropeptides, and their receptors was measured. Lambs born from PFA dams were
      heavier (P < 0.01). There was a time * finishing diet interaction for BW (P =
      0.03), and lambs fed C had a greater BW. Lambs fed C had an increase in DMI (P <
      0.01). There were no significant differences in plasma glucose and NEFA
      concentration (P > 0.1). Lambs born from PFA dams had a greater concentration of
      C22:0 (P < 0.03). Lambs fed C had higher concentrations of C18:1c15 (P < 0.01),
      C17:0 (P < 0.09), C18:0 (P < 0.09), and n6/n3 (P < 0.01). Lambs fed PFA had
      greater concentration (P < 0.05) of C16:1, C22:1, C20:5, C22:5, C22:6, total n3
      FA, and total EPA and DHA. There was a significant dam * finishing diet
      interaction (P <= 0.08) on mRNA concentration for MCR3, CCK-R, Cort-R, and CART.
      Lambs, which had the same treatment as their dams, showed lower overall mRNA
      concentration than those with different treatments between them and their dams.
      Lambs born from PFA ewes had lower concentration of MCR4 mRNA (P = 0.09) than C.
      Agouti-related peptides mRNA concentration was lower in lambs fed PFA (P = 0.06)
      than C. In conclusion, changes on lamb performance, muscle fatty acid
      composition, and metabolic neuropeptides depend not only on the lamb diet, but
      also on the dam diet during late gestation.

PMID- 30239814
TI  - Azithromycin susceptibility in Neisseria gonorrhoeae and seasonal macrolide use.
AB  - Rising azithromycin nonsusceptibility among Neisseria gonorrhoeae threatens
      current treatment recommendations, but the cause of this rise is not well
      understood. We performed an ecological study of seasonal patterns in macrolide
      use and azithromycin resistance in N. gonorrhoeae, finding that population-wide
      macrolide use is associated with increased azithromycin nonsusceptibility. These
      results, indicative of "bystander" selection, have implications for antibiotic
      prescribing guidelines.

PMID- 30239812
TI  - Transcription-driven genome organization: a model for chromosome structure and
      the regulation of gene expression tested through simulations.
AB  - Current models for the folding of the human genome see a hierarchy stretching
      down from chromosome territories, through A/B compartments and topologically
      associating domains (TADs), to contact domains stabilized by cohesin and CTCF.
      However, molecular mechanisms underlying this folding, and the way folding
      affects transcriptional activity, remain obscure. Here we review physical
      principles driving proteins bound to long polymers into clusters surrounded by
      loops, and present a parsimonious yet comprehensive model for the way the
      organization determines function. We argue that clusters of active RNA
      polymerases and their transcription factors are major architectural features;
      then, contact domains, TADs and compartments just reflect one or more loops and
      clusters. We suggest tethering a gene close to a cluster containing appropriate
      factors-a transcription factory-increases the firing frequency, and offer
      solutions to many current puzzles concerning the actions of enhancers, super
      enhancers, boundaries and eQTLs (expression quantitative trait loci). As a
      result, the activity of any gene is directly influenced by the activity of other
      transcription units around it in 3D space, and this is supported by Brownian
      dynamics simulations of transcription factors binding to cognate sites on long
      polymers.

PMID- 30239815
TI  - ABA-driven ripening of fig (Ficus carica L.) fruit governs distinct ripening
      process in reproductive and non-reproductive parts of the syconium.
AB  - The common fig bears a unique closed inflorescence structure, the syconium,
      composed of small individual drupelets that develop from the ovaries enclosed in
      the succulent vegetative-originated receptacle. The fig ripening process is
      traditionally classified as climacteric; however, recent studies have suggested
      distinct mechanisms in its reproductive and non-reproductive parts. We analyzed
      ABA and ethylene production, and expression of ABA-metabolism, ethylene
      biosynthesis, MADS-box, NAC and ethylene-response factor genes in the
      inflorescence and receptacle of on-tree ABA-, ethephon-, fluridone- and NDGA
      treated fruit. Exogenous ABA and ethephon accelerated fruit ripening and
      softening, whereas fluridone and NDGA had the opposite effect, delaying
      endogenous ABA and ethylene production compared to controls. Expression of ABA
      biosynthesis genes FcNCED2 and FcABA2, ethylene-biosynthesis genes FcACS4, FcACOL
      and FcACO2, FcMADS8, 14, 15, FcNAC1, 2, 5, and FcERF9006 was upregulated by
      exogenous ABA and ethephon. NDGA downregulated FcNCED2 and FcABA2, whereas
      fluridone downregulated FcABA2; both downregulated ethylene-related genes. This
      demonstrates the key role of ABA in ripening regulation by promoting ethylene
      production as in climacteric tomato, especially in the inflorescence. However,
      increasing accumulation of endogenous ABA until full ripeness and significantly
      low expression of ethylene-biosynthesis genes in the receptacle suggests non
      climacteric, ABA-dependent ripening in the vegetative-originated succulent
      receptacle fruit part.

PMID- 30239817
TI  - Growth performance, gastrointestinal and digestibility responses in growing pigs
      when fed corn-soybean meal-based diets with corn DDGS treated with fiber
      degrading enzymes with or without liquid fermentation.
AB  - Fermenting high fiber ingredients such as distillers dried grains with solubles
      (DDGS) with feed enzymes may improve their feeding value. We investigated the
      effects of fermenting corn DDGS with a blend of beta-glucanase and xylanases (XB)
      on growth performance, gut parameters, and apparent total tract digestibility
      (ATTD) of nutrients and energy in growing pigs. Dietary treatments were: (1) corn
      soybean meal-based diet + 30% DDGS (control), (2) control + XB without
      fermentation (XBNS), and (3) control + DDGS fermented with XB (16% DM) for 3 to
      10 d at 40  degrees C (XBS). Target activities in XB were 1,050 and 5,500 U/g of
      DDGS for XB, respectively. Diets contained phytase at 750 FTU/kg. Feed samples
      were taken during fermentation and at feeding for analysis of pH and organic
      acids. A total of 144 pigs (25 +/- 1.0 kg BW) were assigned to pens (three
      barrows and three gilts) and allocated to the three diets in a two-phase feeding
      program (3 wk/phase). Diets were fed on ad libitum and were delivered by a
      computer-controlled liquid feeding system at a feed to water ratio of 1:4, four
      times per day. Pigs had free access to water. Fecal samples were taken in the
      final 3 d of phase 2 to determine ATTD using TiO2 marker method and one pig per
      pen was euthanized for gastrointestinal (GIT) measurements. The pH of diets at
      feeding time was lower (P < 0.01) for XBS (4.72) compared with control (5.45) and
      XBNS (5.45). Pigs fed XBNS had higher (P = 0.04) ADG than control in phase 1. In
      phase 2 and the overall (weeks 0 to 6), ADG and final BW were higher (P = 0.01)
      for XBNS than XBS but were not different (P > 0.05) from control. There were no
      diet effects (P > 0.05) on ADFI. Feed to gain (FCR) for XBNS (1.68) and XBS pigs
      (1.69) was better (P < 0.01) than for control pigs (1.78) in phase 1. There were
      no diet effects (P > 0.05) on FCR in phase 2 or in the overall. Pigs fed XBNS had
      lower (P < 0.01) ATTD of CP than control and XBS-fed pigs. Although not different
      (P > 0.05) from control, pigs fed XBNS had lower (P < 0.05) jejunal crypt depth
      and ATTD of gross energy than pigs fed XBS. In conclusion, treating corn DDGS
      with XB with or without liquid fermentation improved feed efficiency in phase 1,
      suggesting degradation of dietary fibrous components that may limit nutrient
      utilization in younger pigs. However, these benefits were not observed in phase
      2.

PMID- 30239816
TI  - A Tomato Tocopherol-Binding Protein Sheds Light on Intracellular alpha-Tocopherol
      Metabolism in Plants.
AB  - Tocopherols are non-polar compounds synthesized in the plastids, which function
      as major antioxidants of the plant cells and are essential in the human diet.
      Both the intermediates and final products of the tocopherol biosynthetic pathway
      must cross plastid membranes to reach their sites of action. So far, no protein
      with tocopherol binding activity has been reported in plants. Here, we
      demonstrated that the tomato SlTBP protein is targeted to chloroplasts and able
      to bind alpha-tocopherol. SlTBP-knockdown tomato plants exhibited reduced levels
      of tocopherol in both leaves and fruits. Several tocopherol deficiency phenotypes
      were apparent in the transgenic lines, such as alterations in photosynthetic
      parameters, dramatic distortion of thylakoid membranes and significant variations
      in the lipid profile. These results, along with the altered expression of genes
      related to photosynthesis, and tetrapyrrole, lipid, isoprenoid,
      inositol/phosphoinositide and redox metabolism, suggest that SlTBP may act in
      conducting tocopherol (or its biosynthetic intermediates) between the plastid
      compartments and/or at the interface between chloroplast and endoplasmic
      reticulum membranes, affecting interorganellar lipid metabolism.

PMID- 30239819
TI  - POSTAR2: deciphering the post-transcriptional regulatory logics.
AB  - Post-transcriptional regulation of RNAs is critical to the diverse range of
      cellular processes. The volume of functional genomic data focusing on post
      transcriptional regulation logics continues to grow in recent years. In the
      current database version, POSTAR2 (http://lulab.life.tsinghua.edu.cn/postar), we
      included the following new features and data: updated ~500 CLIP-seq datasets
      (~1200 CLIP-seq datasets in total) from six species, including human, mouse, fly,
      worm, Arabidopsis and yeast; added a new module 'Translatome', which is derived
      from Ribo-seq datasets and contains ~36 million open reading frames (ORFs) in the
      genomes from the six species; updated and unified post-transcriptional regulation
      and variation data. Finally, we improved web interfaces for searching and
      visualizing protein-RNA interactions with multi-layer information. Meanwhile, we
      also merged our CLIPdb database into POSTAR2. POSTAR2 will help researchers
      investigate the post-transcriptional regulatory logics coordinated by RNA-binding
      proteins and translational landscape of cellular RNAs.

PMID- 30239818
TI  - Generation of an anti-desmoglein 3 antibody without pathogenic activity of
      pemphigus vulgaris for therapeutic application to squamous cell carcinoma.
AB  - It is ideal for the target antigen of a cytotoxic therapeutic antibody against
      cancer to be cancer-specific, but such antigens are rare. Thus an alternative
      strategy for target selection is necessary. Desmoglein 3 (DSG3) is highly
      expressed in lung squamous cell carcinoma, while it is well-known that anti-DSG3
      antibodies cause pemphigus vulgaris, an autoimmune disease. We evaluated DSG3 as
      a novel target by selecting an epitope that exerts efficacy against cancer with
      no pathogenic effects in normal tissues. Pathogenic anti-DSG3 antibodies induce
      skin blisters by inhibiting the cell-cell interaction in a Ca2+-dependent manner.
      We screened anti-DSG3 antibodies that bind DGS3 independent of Ca2+ and have high
      antibody-dependent cell cytotoxicity (ADCC) activity against DSG3-expressing
      cells. These selected antibodies did not inhibit cell-cell interaction and showed
      ADCC activity against squamous cell carcinoma cell lines. Furthermore, one of the
      DSG3 antibodies showed anti-tumour activity in tumour mouse models but did not
      induce adverse effects such as blister formation in the skin. Thus it was
      possible to generate an antibody against DSG3 by using an appropriate epitope
      that retained efficacy with no pathogenicity. This approach of epitope selection
      may expand the variety of druggable target molecules.

PMID- 30239820
TI  - LcbHLH92 from sheepgrass acts as a negative regulator of
      anthocyanin/proanthocyandin accumulation and influences seed dormancy.
AB  - Sheepgrass (Leymus chinensis) is an important native forage grass, and it is
      widely grown in north China. Differential dormancy exists in sheepgrass
      germplasms with different seed colors. To decipher and find potential genes
      underlying this phenomenon, we compared the transcript profiles of yellow seeds
      with weak dormancy and brown seeds with strong dormancy, and we found a
      transcription factor LcbHLH92 which is negatively correlated with those of
      anthocyanin/proanthocyanidin-specific pathway genes, anthocyanidin synthase (ANS)
      and anthocyanidin reductase (ANR). The LcbHLH92 gene had two transcripts,
      LcbHLH92a and LcbHLH92b, and their expression could be induced by ABA, cold and
      NaCl. Overexpression of LcbHLH92a or LcbHLH92b in Arabidopsis significantly
      inhibited the transcript levels of dihydroflavonol reductase (DFR) and ANS genes
      in leaves and seeds, which resulted in a decrease in anthocyanins and
      proanthocyanidins, respectively. Importantly, transgenic Arabidopsis seeds with a
      yellow color showed a higher germination rate than did wild-type controls with a
      brown seed color. Moreover, LcbHLH92a and LcbHLH92b repressed the transcription
      of Transparent Testa8 (TT8), ANS, DFR, and ANR possibly by elevating the
      transcript levels of Jasmonate-ZIM-domain proteins (JAZs) through binding to
      their promoters. In summary, this is the first investigation of LcbHLH92 and its
      relationship to anthocyanin/proanthocyanidin biosynthesis and seed dormancy.

PMID- 30239821
TI  - Carriage of blaKPC-2 by a virulence plasmid in hypervirulent Klebsiella
      pneumoniae.
AB  - Objectives: To characterize a plasmid in a K1 hypervirulent Klebsiella pneumoniae
      (HvKP) strain encoding both hypervirulence and carbapenem resistance phenotypes.
      Methods: Plasmids from HvKP strain KP70-2 were subjected to whole-plasmid
      sequencing using both the Illumina NextSeq 500 sequencing platform and Nanopore
      MinION sequencer platforms. Results: A hybrid virulence- and resistance-encoding
      plasmid of 240 kb, harbouring both the virulence gene rmpA2 and the carbapenemase
      gene blaKPC-2, was recovered from a clinical HvKP strain. Designated pKP70-2, the
      plasmid was found to be almost structurally identical to various known
      hypervirulence-encoding plasmids harboured by other HvKP strains, except for an
      extra MDR-encoding region located within the genetically conserved plasmid
      backbone. This MDR region was flanked by two copies of IS26 in the same
      orientation, one at each end and linked to an external 8 bp (CTAAAATT) product of
      target site duplications, suggesting that an insertion event was responsible for
      the integration of the MDR region into the virulence plasmid. The MDR region was
      also found to harbour mobile elements that in turn contain the antibiotic
      resistance genes dfrA14 and blaKPC-2. Conclusions: Based on the genetic
      composition of pKP70-2, we postulate that the multiple insertion elements that it
      harbours were responsible for mediating the plasmid recombination events that
      underlie continuous emergence and genetic adaptation of novel resistance- and
      virulence-encoding mobile elements in K. pneumoniae.

PMID- 30239822
TI  - Exploring Lived Experiences of Chronic Pain Through Photo-Elicitation and Social
      Networking.
AB  - Objective: To understand how patients' use of photo-elicitation and online social
      networks (Facebook) enhances their understanding of what it means to live with
      pain. Design: Qualitative substudy of the intervention arm of a randomized trial.
      Setting/Subjects: Primary care patients living with pain drawn from nine family
      practices with at least two pain visits in the last six months. Methods: The
      private Facebook group was co-facilitated by a moderator and a patient
      investigator who lives with chronic pain. Patients were asked to share photos
      that elicit their lived experience with chronic pain, and facilitators guided
      participants in ongoing discussion about these photos, and thus the life with
      pain. Facebook discussions were analyzed via Dedoose (a qualitative analysis
      software) using thematic analysis. Results: Discussions of photos elicited three
      overarching themes regarding patients' lived experience with chronic pain: 1)
      patients' redefined pain identity; 2) pain interference with enjoyment of life
      and activities; and 3) patients' diminished ability to function. Conclusions:
      Photo-elicitation is an innovative way to shed light on patients' lived
      experience with chronic pain. Despite some technical challenges, Facebook support
      groups utilizing photo-elicitation can provide a readily available platform that
      can facilitate interchange of patient experiences and might help patients
      communicate with their providers.

PMID- 30239823
TI  - Transcatheter and minimally invasive surgical left ventricular reconstruction for
      the treatment of ischaemic cardiomyopathy: preliminary results.
AB  - OBJECTIVES: Adverse remodelling of the left ventricle (LV) after myocardial
      infarction (MI) results in a pathological increase in LV volume and reduction in
      LV ejection fraction (EF). We describe the preliminary results of a novel,
      multicentre, combined transcatheter and minimally invasive technique to
      reconstruct the remodelled LV by plication and exclusion of the scar, and to
      reduce the excess volume, resulting in decreased wall stress and increased EF.
      METHODS: A novel hybrid transcatheter technique that relies on microanchoring
      technology (Revivent TCTM System, BioVentrix Inc., San Ramon, CA, USA) was used.
      The LV is reconstructed without the use of extracorporeal circulation by
      plication of the fibrous scar. This is achieved by implantation of a series of
      internal and external microanchors brought together over a PEEK (poly-ether-ether
      ketone) tether to form a longitudinal line of apposition between the LV free wall
      and the anterior septum. Internal anchors are deployed by a transcatheter
      technique on the right side of the ventricular septum through the right internal
      jugular vein. Paired external anchors are advanced through a left-sided
      minithoracotomy and deployed on the LV epicardium. A specialized force gauge is
      used to bring these 'right ventricle (RV)-LV' anchors together under measured
      compression forces. LV-LV' anchor pairs through the LV apex beyond the distal tip
      of the RV complete the reconstruction. Patients who were considered eligible for
      the procedure presented with symptomatic heart failure (New York Heart
      Association class >=II) and ischaemic cardiomyopathy (EF <40%) after anteroseptal
      MI. All patients had a dilated LV with either an a- or dys-kinetic scar in the
      anteroseptal wall and apex of >=50% transmurality. RESULTS: Between October 2016
      and April 2017, 9 patients (8 men, 1 woman; mean age 60 +/- 8 years) were
      operated on in 2 Dutch centres. Procedural success was 100%. On average, 2.6
      anchor pairs were used to reconstruct the LV. Comparing echocardiographic data
      preoperatively and directly postoperatively, LV ejection fraction increased from
      28 +/- 8% to 40 +/- 10% (change +43%, P < 0.001) and LV volumes decreased LV end
      systolic volume index 53 +/- 8 ml/m2 to 30 +/- 11 ml/m2 (change -43%, P < 0.001)
      and LVEDVI 75 +/- 23 ml/m2 to 45 +/- 6 ml/m2 (change -40%, P = 0.001). In 1
      patient, an RV perforation occurred which necessitated conversion to full
      sternotomy. One patient underwent a postoperative revision because of RV
      restriction. After the removal of 1 'RV-LV' anchor pair, the patient recovered
      completely. Hospital mortality was 0%. The median duration of intensive care unit
      stay was 2 days [interquartile range (IQR) 1-46 days], and the median length of
      hospital stay was 9 days (IQR 3-57 days). CONCLUSIONS: Hybrid transcatheter LV
      reconstruction is a promising novel treatment option for patients with
      symptomatic heart failure and ischaemic cardiomyopathy after anteroseptal MI. The
      early results demonstrate that the procedure is safe and results in a significant
      improvement in EF and reduction in LV volumes in the early postoperative period.

PMID- 30239824
TI  - Endocrine Therapy Nonadherence and Discontinuation in Black and White Women.
AB  - Background: Differential use of endocrine therapy (ET) by race may contribute to
      breast cancer outcome disparities, but racial differences in ET behaviors are
      poorly understood. Methods: Women aged 20-74 years with a first primary, stage I
      III, hormone receptor-positive (HR+) breast cancer were included. At 2 years
      postdiagnosis, we assessed nonadherence, defined as not taking ET every day or
      missing more than two pills in the past 14 days, discontinuation, and a composite
      measure of underuse, defined as either missing pills or discontinuing completely.
      Using logistic regression, we evaluated the relationship between race and
      nonadherence, discontinuation, and overall underuse in unadjusted, clinically
      adjusted, and socioeconomically adjusted models. Results: A total of 1280 women
      were included; 43.2% self-identified as black. Compared to white women, black
      women more often reported nonadherence (13.7% vs 5.2%) but not discontinuation
      (10.0% vs 10.7%). Black women also more often reported the following: hot
      flashes, night sweats, breast sensitivity, and joint pain; believing that their
      recurrence risk would not change if they stopped ET; forgetting to take ET; and
      cost-related barriers. In multivariable analysis, black race remained
      statistically significantly associated with nonadherence after adjusting for
      clinical characteristics (adjusted odds ratio = 2.72, 95% confidence interval =
      1.75 to 4.24) and after adding socioeconomic to clinical characteristics
      (adjusted odds ratio = 2.44, 95% confidence interval = 1.50 to 3.97) but was not
      independently associated with discontinuation after adjustment. Low recurrence
      risk perception and lack of a shared decision making were strongly predictive of
      ET underuse across races. Conclusions: Our results highlight important racial
      differences in ET-adherence behaviors, perceptions of benefits/harms, and shared
      decision making that may be targeted with culturally tailored interventions.

PMID- 30239825
TI  - A Formula to Identify Potential Cases of beta-Thalassemia/HbE Disease Among
      Patients With Absent HbA, HbE >75% and HbF Between 5 and 15.
AB  - Objective: To establish a simple formula to be used for discrimination between
      beta-thalassemia/hemoglobin E (beta-thal/HbE) and homozygous hemoglobin (Hb)E in
      specimens with absent hemoglobin (Hb)A, HbE of greater than 75%, and HbF between
      5% and 15%. Methods: We analyzed laboratory results from February 2015 through
      February 2018. Molecular analysis for diagnosis of beta-thal mutation and HbE was
      performed in specimens that contained HbE of greater than 75% and HbF from 5% to
      15%, as measured by high-performance liquid chromatography (HPLC). HbA2 and HbF
      levels were also measured by capillary electrophoresis. Then, the formula (6 *
      HbA2 + HbF)/MCV was developed. Results: The score of 0.9 or higher was found in
      all 19 beta-thal/HbE specimens (100%) and only 8 of 65 homozygous HbE specimens
      (12.3%). Also, the formula yielded 90.5% efficiency in identifying beta-thal/HbE
      disease, and the efficiency was found to be higher compared with when the HbA2
      value of greater than 6% was used by itself (85.4%). Conclusion: The formula (6 *
      HbA2 + HbF)/MCV, with a cutoff point at 0.9, could identify the potential cases
      of beta-thal/HbE disease among patients with absent HbA, HbE of greater than 75%,
      and HbF between 5% and 15%.

PMID- 30239826
TI  - The role of endoscopic evaluation for radiation proctitis in patients receiving
      intermediate-dose postoperative radiotherapy for rectal cancer.
AB  - Objectives: High-dose pelvic radiotherapy (RT) is known to be associated with
      chronic radiation proctitis (RP). However, the effects of intermediate radiation
      doses are unknown. We assessed the incidence of late clinical RP among patients
      with rectal cancer receiving intermediate-dose postoperative RT, as well as the
      role of early endoscopic abnormalities in predicting RP development. Methods: We
      retrospectively reviewed 153 patients with rectal cancer who received
      postoperative RT at a median dose of 54 Gy between 2005 and 2009 and who
      underwent endoscopic examination within 12 months thereafter. Endoscopic RP was
      assessed using the Vienna rectoscopy score (VRS). Late clinical RP toxicity was
      evaluated, as was its correlation with endoscopic RP. Results: All patients
      underwent an endoscopic examination at a median of 9 months after postoperative
      pelvic RT. Endoscopic RP was detected in 45 patients (29.4%); the predominant
      patterns were telangiectasia and congested mucosa. During the median 88-month
      follow-up period, 29 patients (19.0%) experienced late clinical RP; only 3 (2.0%)
      had Grade 3 or above. The VRS predicted the development of late clinical RP as
      well as its cumulative incidence (P < 0.001). Endoscopic evidence of
      telangiectasia was significantly associated with the development of late clinical
      RP (P < 0.001). Conclusions: Early endoscopic findings using VRS are useful for
      predicting the possibility of late clinical RP, although the incidences of severe
      cases were low. Patients with endoscopic abnormalities should be followed closely
      owing to their susceptibility to clinical RP.

PMID- 30239827
TI  - Comparative Mitogenomic Analysis of Forensically Important Sarcophagid Flies
      (Diptera: Sarcophagidae) and Implications of Species Identification.
AB  - The flesh flies (Diptera: Sarcophagidae) are significant in forensic
      investigations. The mitochondrial genome (mitogeome) has been widely used as
      genetic markers for phylogenetic analysis and species identification. To further
      understand the mitogenome-level features in Sarcophagidae, the complete
      mitogenome of Sarcophaga formosensis (Kirneret Lopes, 1961) (Diptera:
      Sarcophagidae) and Sarcophaga misera (Walker, 1849) (Diptera: Sarcophagidae) was
      firstly sequenced, annotated, and compared with other 13 Sarcophagidae species.
      The result indicated that the gene arrangement, gene content, base composition,
      and codon usage were conserved in the ancestral arthropod. Evolutionary rate of
      the mitogenome fragments revealed that the nonsynonymous and synonymous
      substitution rates (Ka and Ks) ratio was less than 1.00, indicating these
      variable sites under strong purifying selection. Almost all transfer RNA genes
      (tRNAs) have typical clover-leaf structures within these sarcophagid mitogenomes,
      except tRNA-Ser (AGN) is lack of the dihydrouridine arm. This comparative
      mitogenomic analysis sheds light on the architecture and evolution of mitogenomes
      in the Sarcophagidae. Phylogenetic analyses containing the interspecific
      distances from different regions in these species provided us new insights into
      the application of these effective genetic markers for species identification of
      flesh flies.

PMID- 30239830
TI  - FUT2 secretor status is not associated with oral poliovirus vaccine
      immunogenicity in south Indian infants.
AB  - The FUT2 gene determines whether histo-blood group antigens are secreted at
      mucosal surfaces. Secretor status influences susceptibility to enteric viruses,
      potentially including oral poliovirus vaccine (OPV). We performed a nested case
      control study to determine the association between FUT2 genotype (SNPs G428A,
      C302T, and A385T) and seroconversion among Indian infants who received a single
      dose of monovalent type 3 OPV. Secretor prevalence was 89/118 (75%) in infants
      who seroconverted and 97/122 (80%) in infants who failed to seroconvert (odds
      ratio 0.79, 95% CI 0.43-1.45). Our findings suggest that FUT2 genotype is not a
      key determinant of variation in OPV immunogenicity.

PMID- 30239829
TI  - Effect of efavirenz-based antiretroviral therapy and high-dose rifampicin on the
      pharmacokinetics of isoniazid and acetyl-isoniazid.
AB  - Objectives: To describe the pharmacokinetics of isoniazid and acetyl-isoniazid in
      TB/HIV-coinfected patients, and assess the effects of efavirenz co-administration
      and a 50% increase in the dose of rifampicin on the pharmacokinetic parameters of
      isoniazid and acetyl-isoniazid. Methods: TB/HIV-coinfected patients participating
      in the three-treatment-arm RAFA randomized controlled trial conducted in West
      Africa were recruited into the pharmacokinetics sub-study. Five serial blood
      samples were collected on a single visit between 4 and 8 weeks after initiation
      of antituberculosis treatment. Concentration-time data for isoniazid and acetyl
      isoniazid were analysed using non-linear mixed-effects models. Results: Isoniazid
      concentrations from 150 patients were available for analysis, and 79 of these
      (53%) also had concentrations of acetyl-isoniazid. Isoniazid pharmacokinetics was
      best described with a two-compartment disposition model with lagged first-order
      absorption and elimination using a semi-mechanistic model describing hepatic
      extraction. The model identified two elimination pathways, separating formation
      of acetyl-isoniazid from other routes of metabolism. The predicted AUC0-24 is
      reduced by 29% in patients who are fast acetylators of isoniazid and receiving
      efavirenz-based ART (6.73 versus 4.68 mg.h/L). In slow acetylators, efavirenz
      based ART had no effect on isoniazid exposure (AUC0-24 = 17.5 mg.h/L).
      Conclusions: Efavirenz-based ART affects the acetylation metabolic pathway
      amongst rapid acetylators, resulting in reduced exposure to isoniazid.
      Pharmacokinetics of isoniazid and acetyl-isoniazid were not influenced by the 50%
      increase in rifampicin dose.

PMID- 30239828
TI  - A Rev-CBP80-eIF4AI complex drives Gag synthesis from the HIV-1 unspliced mRNA.
AB  - Gag synthesis from the full-length unspliced mRNA is critical for the production
      of the viral progeny during human immunodeficiency virus type-1 (HIV-1)
      replication. While most spliced mRNAs follow the canonical gene expression
      pathway in which the recruitment of the nuclear cap-binding complex (CBC) and the
      exon junction complex (EJC) largely stimulates the rates of nuclear export and
      translation, the unspliced mRNA relies on the viral protein Rev to reach the
      cytoplasm and recruit the host translational machinery. Here, we confirm that Rev
      ensures high levels of Gag synthesis by driving nuclear export and translation of
      the unspliced mRNA. These functions of Rev are supported by the CBC subunit
      CBP80, which binds Rev and the unspliced mRNA in the nucleus and the cytoplasm.
      We also demonstrate that Rev interacts with the DEAD-box RNA helicase eIF4AI,
      which translocates to the nucleus and cooperates with the viral protein to
      promote Gag synthesis. Finally, we show that the Rev/RRE axis is important for
      the assembly of a CBP80-eIF4AI complex onto the unspliced mRNA. Together, our
      results provide further evidence towards the understanding of the molecular
      mechanisms by which Rev drives Gag synthesis from the unspliced mRNA during HIV-1
      replication.

PMID- 30239831
TI  - A-Kinase Anchoring Protein 13 (AKAP13) Augments Progesterone Signaling in Uterine
      Fibroid Cells.
AB  - Context: Uterine leiomyomata (fibroids) are prevalent, sex hormone-dependent
      tumors with an altered response to mechanical stress. Ulipristal acetate, a
      selective progesterone receptor modulator (SPRM), significantly reduces fibroid
      size in patients. However, progesterone receptor signaling in fibroids and its
      relationship to mechanical signaling is incompletely understood. Objective: Our
      prior studies revealed that A-kinase Anchoring Protein 13 (AKAP13) was
      overexpressed in fibroids and contributed to altered mechanotransduction in
      fibroids. Since AKAP13 augmented nuclear receptor signaling in other tissues, we
      sought to determine whether AKAP13 might influence progesterone receptor
      signaling in fibroids. Methods and Results: Fibroid samples from patients treated
      with ulipristal acetate or placebo were examined for AKAP13 expression by
      immunohistochemistry. In immortalized uterine fibroid cell lines and COS-7 cells,
      we observed that AKAP13 increased ligand-dependent progesterone receptor (PR)
      activation of luciferase reporters and endogenous progesterone-responsive genes
      for PR-B, but not PR-A. Inhibition of extracellular signaling-regulated kinase
      (ERK) reduced activation of PR-dependent signaling by AKAP13, but inhibition of
      p38 mitogen-activated protein kinase had no effect. Additionally, GST binding
      assays revealed that AKAP13 bound to PR-B through its carboxyl terminus.
      Conclusion: These data suggest an intersection of mechanical signaling and
      progesterone receptor signaling involving AKAP13 through ERK. Further elucidation
      of the integration of mechanical and hormonal signaling pathways in fibroids may
      provide insight to fibroid development and suggest new therapeutic strategies for
      treatment.

PMID- 30239832
TI  - Long-Term Antibody Response to Human Papillomavirus Vaccines: up to 12 Years
      Follow-Up in the Finnish Maternity Cohort.
AB  - Background: Most cervical cancers are caused by vaccine-preventable infections
      with human papillomaviruses (HPV). HPV prophylactic vaccines GardasilTM and
      CervarixTM have been widely used for >10 years and are reported to induce high
      antibody levels. A head-to-head comparison of the antibody responses induced by
      the two vaccines has been performed only up to 5 years. Methods: Virtually all
      3,300 16- to 17-year-old Finnish females, who got one of the two HPV vaccines in
      phase III licensure trials, consented to registry-based long-term follow-up.
      Linkage with the Finnish Maternity Cohort found that they donated >2,500 serum
      samples up to 12 years later. Sera of 337 (38.6%) GardasilTM and 730 (30.3%)
      CervarixTM vaccine recipients were retrieved and HPV type-specific antibody
      levels were determined using in-house multiplexed heparin-HPV Pseudovirion
      Luminex assay. Results: HPV16 and HPV18 antibody levels remained stable and above
      natural infection-related antibody levels for up to 12 years for most vaccine
      recipients. The median antibody levels were higher among CervarixTM recipients 7
      to 12 years post vaccination (p<0.0001). Conclusions: The stability of vaccine
      induced antibody levels is in accordance with the high long-term protection
      reported previously. The differences in antibody levels induced by the two
      vaccines imply that continued follow-up to identify possible breakthrough cases
      and estimation of the minimal protective levels of serum antibodies is a research
      priority.

PMID- 30239833
TI  - Plasmodium falciparum activates CD16+ dendritic cells to produce TNF and IL-10 in
      subpatent malaria.
AB  - The malaria causing parasite Plasmodium subverts host immune responses by several
      strategies including the modulation of dendritic cells (DCs). Here, we show P.
      falciparum skewed CD16+ DC cytokine responses towards IL-10 production in vitro,
      distinct to the cytokine profile induced by toll-like receptor ligation. To
      determine CD16+ DC responsiveness in vivo, we assessed their function following
      induced P. falciparum infection in malaria-naive volunteers. CD16+ DCs underwent
      distinctive activation, with increased expression of maturation markers HLA-DR
      and CD86, enhanced TNF production and co-production of TNF/IL-10. In vitro re
      stimulation with P. falciparum further increased IL-10 production. In contrast,
      during naturally acquired malaria episode CD16+ DCs showed diminished maturation,
      suggesting increased parasite burden and previous exposure influence DC subset
      function. These findings identify CD16+ DCs as the only DC subset activated
      during primary blood-stage human Plasmodium infection. As dual cytokine producers
      CD16+ DCs contribute to inflammatory as well as regulatory innate immune
      processes.

PMID- 30239834
TI  - European multicentre study validates enhanced liver fibrosis test as biomarker of
      fibrosis in systemic sclerosis.
AB  - Objectives: To validate enhanced liver fibrosis (ELF) test and its components
      amino-terminal propeptide of procollagen type III (PIIINP), tissue inhibitor of
      matrix metalloproteinase-1 (TIMP-1) and HA-as biomarkers of fibrosis in SSc in an
      independent, international, multicentre cohort. Methods: Two hundred and fifty
      four SSc patients from six Rheumatology Centres were included. Sera were
      collected and stored according to EUSTAR biobanking recommendations and analysed
      through automated high throughput diagnostics. Statistical analysis was performed
      with SPSS software. Results: Two hundred and forty-seven SSc patients (mean age
      55.7 +/- 13.9 years, 202 F) were analysed. ELF score, TIMP-1 and PIIINP levels
      were higher in males (P = 0.0197, P = 0.0107, P = 0.0108 respectively) and in
      dcSSc (P = 0.001, P = 0.0008, P < 0.0001 respectively). ELF score and the single
      markers significantly correlated with modified Rodnan skin score (r = 0.37, P <
      0.0001), disease activity and severity (P < 0.0001 for all markers, except for HA
      P = 0.0001) and inversely with forced vital capacity, (FVC) % (TIMP-1, r = -0.21,
      P = 0.0012; PIIINP, r = -0.26, P = 0.0001), TLC% (ELF score, r = -0.20, P =
      0.0036; TIMP-1, r = -0.32, P < 0.0001; PIIINP, r = -0.28, P < 0.0001), diffusion
      capacity of the lung for carbon monoxide (DLCO) % (P < 0.0001 for all markers,
      except for HA P = 0.0115). Multivariate analysis indicated that age (P < 0.001),
      modified Rodnan skin score (P < 0.001) and DLCO% (P = 0.005) were independently
      associated with ELF score. Conclusion: Between the first and this validation
      studies, the value of the ELF score as independent marker of skin and lung
      involvement in SSc is confirmed in 457 patients. A longitudinal study is on-going
      to identify an SSc specific algorithm with predictive value for skin and lung
      progression.

PMID- 30239835
TI  - Bronchoalveolar lavage proteomic analysis in pulmonary fibrosis associated with
      systemic sclerosis: S100A6 and 14-3-3epsilon as potential biomarkers.
AB  - Objective: SSc is a rare severe connective tissue disorder. Its prognosis is
      mainly related to the development of pulmonary fibrosis (PF)-SSc and pulmonary
      arterial hypertension. No known therapy for PF-SSc modifies progressive lung
      fibrotic involvement. Research is therefore aimed at a deeper understanding of
      complex pathogenetic mechanisms and the possibility of new prognostic biomarkers
      and therapeutic targets. Methods: Towards the first of these aims, we conducted
      functional proteomic analysis of bronchoalveolar lavage samples from PF-SSc
      patients and smoker and non-smoker controls. Results: The differential expression
      pattern revealed by principal component analysis highlighted a specific protein
      profile of PF-SSc with respect to control samples, and enrichment analysis shed
      light on process networks involved in pathogenesis. The proteins identified are
      known to be involved in lung inflammation of PF-SSc-induced IL6 signalling, the
      complement system, innate immunity, Jak-STAT, the kallikrein-kinin system, blood
      coagulation, the immune response mediated by phagocytosis and phagosomes in
      antigen presentation. In particular, our MetaCore network suggested C3a, APOAI,
      14-3-3epsilon, SPFA2 and S100A6 as potential biomarkers; these are upstream
      molecules involved in lung fibrosis, innate immunity and vascular damage
      occurring in PF-SSc. Conclusion: This report provides a molecular overview of
      pathological processes in PF-SSc, pinpointing possible new disease biomarkers and
      therapeutic targets.

PMID- 30239837
TI  - All-cause mortality in relation to changes in relative blood volume during
      hemodialysis.
AB  - Background: Relative blood volume (RBV) monitoring is widely used in hemodialysis
      (HD) patients, yet the association between intradialytic RBV and mortality is
      unknown. Methods: Intradialytic RBV was recorded once/min during a 6-month
      baseline period; all-cause mortality was noted during follow-up. RBV at 1, 2 and
      3 h into HD served as a predictor of all-cause mortality during follow-up. We
      employed Kaplan-Meier analysis, univariate and adjusted Cox proportional hazards
      models for survival analysis. Results: We studied 842 patients. During follow-up
      (median 30.8 months), 249 patients (29.6%) died. The following hourly RBV ranges
      were associated with improved survival: first hour, 93-96% [hazard ratio (HR)
      0.58 (95% confidence interval (CI) 0.42-0.79)]; second hour, 89-94% [HR 0.54 (95%
      CI 0.39-0.75)]; third hour, 86-92% [HR 0.46 (95% CI 0.33-0.65)]. In about one
      third of patients the RBV was within these ranges and in two-thirds it was above.
      Subgroup analysis by median age (<=/> 61 years), sex, race (white/nonwhite),
      predialysis systolic blood pressure (SBP; <=/> 130 mmHg) and median interdialytic
      weight gain (<=/> 2.3 kg) showed comparable favorable RBV ranges. Patients with a
      3-h RBV between 86 and 92% were younger, had higher ultrafiltration volumes and
      rates, similar intradialytic average and nadir SBPs and hypotension rates, lower
      postdialysis SBP and a lower prevalence of congestive heart failure when compared
      with patients with an RBV >92%. In the multivariate Cox analysis, RBV ranges
      remained independent and significant outcome predictors. Conclusion: Specific
      hourly intradialytic RBV ranges are associated with lower all-cause mortality in
      chronic HD patients.

PMID- 30239836
TI  - The Epidemiology of Cholera in Zanzibar: Implications for the Zanzibar
      Comprehensive Cholera Elimination Plan.
AB  - Background: Cholera poses a public health and economic threat to Zanzibar.
      Detailed epidemiologic analyses are needed to inform a multisectoral cholera
      elimination plan currently under development. Methods: We collated passive
      surveillance data from 1997 to 2017 and calculated the outbreak-specific and
      cumulative incidence of suspected cholera per shehia (neighborhood). We explored
      the variability in shehia-specific relative cholera risk and explored the
      predictive power of targeting intervention at shehias based on historical
      incidence. Using flexible regression models, we estimated cholera's seasonality
      and the relationship between rainfall and cholera transmission. Results: From
      1997 and 2017, 11921 suspected cholera cases were reported across 87% of
      Zanzibar's shehias, representing an average incidence rate of 4.4 per 10000/year.
      The geographic distribution of cases across outbreaks was variable, although a
      number of high-burden areas were identified. Outbreaks were highly seasonal with
      2 high-risk periods corresponding to the annual rainy seasons. Conclusions:
      Shehia-targeted interventions should be complemented with island-wide cholera
      prevention activities given the spatial variability in cholera risk from outbreak
      to outbreak. In-depth risk factor analyses should be conducted in the high-burden
      shehias. The seasonal nature of cholera provides annual windows of opportunity
      for cholera preparedness activities.

PMID- 30239838
TI  - Serologic Markers for Ebolavirus Among Healthcare Workers in the Democratic
      Republic of the Congo.
AB  - Healthcare settings have played a major role in propagation of Ebola virus (EBOV)
      outbreaks. Healthcare workers (HCWs) have elevated risk of contact with EBOV
      infected patients, particularly if safety precautions are not rigorously
      practiced. We conducted a serosurvey to determine seroprevalence against multiple
      EBOV antigens among HCWs of Boende Health Zone, Democratic Republic of the Congo,
      the site of a 2014 EBOV outbreak. Interviews and specimens were collected from
      565 consenting HCWs. Overall, 234 (41.4%) of enrolled HCWs were reactive to at
      least 1 EBOV protein: 159 (28.1%) were seroreactive for anti-glycoprotein
      immunoglobulin G (IgG), 89 (15.8%) were seroreactive for anti-nucleoprotein IgG,
      and 54 (9.5%) were VP40 positive. Additionally, sera from 16 (2.8%) HCWs
      demonstrated neutralization capacity. These data demonstrate that a significant
      proportion of HCWs have the ability to neutralize virus, despite never having
      developed Ebola virus disease symptoms, highlighting an important and poorly
      documented aspect of EBOV infection and progression.

PMID- 30239840
TI  - Intratumoral Heterogeneity of Glioblastoma Infiltration Revealed by Joint
      Histogram Analysis of Diffusion Tensor Imaging.
AB  - Background: Glioblastoma is a heterogeneous disease characterized by its
      infiltrative growth, rendering complete resection impossible. Diffusion tensor
      imaging (DTI) shows potential in detecting tumor infiltration by reflecting
      microstructure disruption. OBJECTIVE: To explore the heterogeneity of
      glioblastoma infiltration using joint histogram analysis of DTI, to investigate
      the incremental prognostic value of infiltrative patterns over clinical factors,
      and to identify specific subregions for targeted therapy. Methods: A total of 115
      primary glioblastoma patients were prospectively recruited for surgery and
      preoperative magnetic resonance imaging. The joint histograms of decomposed
      anisotropic and isotropic components of DTI were constructed in both contrast
      enhancing and nonenhancing tumor regions. Patient survival was analyzed with
      joint histogram features and relevant clinical factors. The incremental
      prognostic values of histogram features were assessed using receiver operating
      characteristic curve analysis. The correlation between the proportion of
      diffusion patterns and tumor progression rate was tested using Pearson
      correlation. Results: We found that joint histogram features were associated with
      patient survival and improved survival model performance. Specifically, the
      proportion of nonenhancing tumor subregion with decreased isotropic diffusion and
      increased anisotropic diffusion was correlated with tumor progression rate (P =
      .010, r = 0.35), affected progression-free survival (hazard ratio = 1.08, P <
      .001), and overall survival (hazard ratio = 1.36, P < .001) in multivariate
      models. Conclusion: Joint histogram features of DTI showed incremental prognostic
      values over clinical factors for glioblastoma patients. The nonenhancing tumor
      subregion with decreased isotropic diffusion and increased anisotropic diffusion
      may indicate a more infiltrative habitat and potential treatment target.

PMID- 30239841
TI  - Comparison of Seated With Recumbent Saline Suppression Testing for the Diagnosis
      of Primary Aldosteronism.
AB  - Context: Failure of plasma aldosterone suppression during fludrocortisone
      suppression testing (FST) or saline suppression testing (SST) confirms primary
      aldosteronism (PA). Aldosterone is often higher upright than recumbent in PA;
      upright levels are used during FST. In a pilot study (24 patients with PA),
      seated saline suppression testing (SSST) was more sensitive than recumbent saline
      suppression testing (RSST). Objective, Design, and Patients: The current
      validation study involved 100 patients who underwent FST, RSST, and SSST, eight
      before and after unilateral adrenalectomy. Of the 108 FSTs, 73 confirmed and 18
      excluded PA. Four patients with inconclusive FST lateralized on adrenal venous
      sampling, making a total of 77 with PA. Results: The area under the receiver
      operating characteristic (ROC) curve was greater for SSST than RSST (0.96 vs.
      0.80; P < 0.01). ROC analysis predicted optimal cutoff aldosterone levels of 162
      pmol/L for SSST and 106 pmol/L for RSST. At these cutoffs, SSST showed high
      sensitivity for PA (87%) that markedly exceeded that for RSST (38%; P < 0.001)
      but similar specificity (94 vs. 94%; not significant). SSST was more sensitive
      than RSST in detecting both unilateral (n = 28, 93% vs. 68%, P < 0.05) and
      bilateral (n = 40, 85% vs. 20%, P < 0.001) forms of PA. Only three SSST (vs. 9
      RSST and 17 FST) results were inconclusive. Conclusions: SSST is highly sensitive
      and superior to RSST in identifying both unilateral and bilateral forms of PA and
      has a low rate of false positives and inconclusive results. It therefore offers a
      reliable and much less complicated and expensive alternative to FST for
      confirming PA.

PMID- 30239839
TI  - Transcript availability dictates the balance between strand-asynchronous and
      strand-coupled mitochondrial DNA replication.
AB  - Mammalian mitochondria operate multiple mechanisms of DNA replication. In many
      cells and tissues a strand-asynchronous mechanism predominates over coupled
      leading and lagging-strand DNA synthesis. However, little is known of the factors
      that control or influence the different mechanisms of replication, and the idea
      that strand-asynchronous replication entails transient incorporation of
      transcripts (aka bootlaces) is controversial. A firm prediction of the bootlace
      model is that it depends on mitochondrial transcripts. Here, we show that
      elevated expression of Twinkle DNA helicase in human mitochondria induces
      bidirectional, coupled leading and lagging-strand DNA synthesis, at the expense
      of strand-asynchronous replication; and this switch is accompanied by decreases
      in the steady-state level of some mitochondrial transcripts. However, in the so
      called minor arc of mitochondrial DNA where transcript levels remain high, the
      strand-asynchronous replication mechanism is instated. Hence, replication
      switches to a strand-coupled mechanism only where transcripts are scarce, thereby
      establishing a direct correlation between transcript availability and the
      mechanism of replication. Thus, these findings support a critical role of
      mitochondrial transcripts in the strand-asynchronous mechanism of mitochondrial
      DNA replication; and, as a corollary, mitochondrial RNA availability and RNA/DNA
      hybrid formation offer means of regulating the mechanisms of DNA replication in
      the organelle.

PMID- 30239842
TI  - Intravaginal Testosterone Improves Sexual Satisfaction and Vaginal Symptoms
      Associated With Aromatase Inhibitors.
AB  - Context: Intravaginal testosterone (IVT) is a potential treatment of vulvovaginal
      atrophy (VVA) associated with aromatase inhibitor (AI) use. Objective: To
      investigate the effects of IVT on sexual satisfaction, vaginal symptoms, and
      urinary incontinence (UI) associated with AI use. Design: Double-blind,
      randomized, placebo-controlled trial. Setting: Academic clinical research center.
      Participants: Postmenopausal women taking an AI with VVA symptoms. Intervention:
      IVT cream (300 MUg per dose) or identical placebo, self-administered daily for 2
      weeks and then thrice weekly for 24 weeks. Main Outcomes and Measures: The
      primary outcome was the change in the sexual satisfaction score on the Female
      Sexual Function Index (FSFI). Secondary outcomes included vaginal symptoms and
      responses to the Profile of Female Sexual Function, the Female Sexual Distress
      Scale-Revised (FSDS-R), and the Questionnaire for UI Diagnosis. Serum sex
      steroids were measured. Results: A total of 44 women were randomly assigned and
      37 provided evaluable data, (mean age 56.4 years, SD 8.8 years). At 26 weeks, the
      mean between-group difference in the baseline-adjusted change in FSFI
      satisfaction scores was significantly greater for the IVT group than the placebo
      group (mean difference 0.73 units; 95% CI, 0.02 to 1.43; P = 0.043). IVT cream
      resulted in significant improvements, compared with placebo, in FSDS-R scores (P
      = 0.02), sexual concerns (P < 0.001), sexual responsiveness (P < 0.001), vaginal
      dryness (P = 0.009), and dyspareunia (P = 0.014). Serum sex steroid levels did
      not change. Few women had UI symptoms, with no treatment effect. Conclusion: IVT
      significantly improved sexual satisfaction and reduced dyspareunia in
      postmenopausal women on AI therapy. The low reporting of UI among women on AI
      therapy merits further investigation.

PMID- 30239844
TI  - Learning to travel: reducing the health risks of study abroad opportunities.

PMID- 30239845
TI  - The SLC transporter in nutrient and metabolic sensing, regulation, and drug
      development.
AB  - The prevalence of metabolic diseases is growing worldwide. Accumulating evidence
      suggests that solute carrier (SLC) transporters contribute to the aetiology of
      various metabolic diseases. Consistent with metabolic characteristics, the top 5
      organs in which SLC transporters are highly expressed are the kidney, brain,
      liver, gut, and heart. Our long-term research goals are to understand the
      molecular mechanisms of important SLC transporter-mediated physiological
      processes and their potentials as drug targets. SLC transporters serve as
      "metabolic gate" of cells and mediate the transport of a wide range of essential
      nutrients and metabolites such as glucose, amino acids, vitamins,
      neurotransmitters, and inorganic/metal ions. Gene-modified animal models have
      demonstrated that SLC transporters participate in many important physiological
      functions including nutrient supply, metabolic transformation, energy
      homeostasis, tissue development, oxidative stress, host defense, and neurological
      regulation. Furthermore, the human genomic studies have identified that SLC
      transporters are susceptible or causative genes in various diseases like cancer,
      metabolic disease, cardiovascular disease, immunological disorders, and
      neurological dysfunction. Importantly, a number of SLC transporters have been
      successfully targeted for drug developments. This review will focus on the
      current understanding of SLCs in regulating physiology, nutrient sensing and
      uptake, and risk of diseases.

PMID- 30239846
TI  - The alleviative effects and related mechanisms of taurine supplementation on
      growth performance and carcass characteristics in broilers exposed to chronic
      heat stress.
AB  - To investigate the alleviative effects and molecular mechanisms of taurine
      supplementation on growth performance and carcass characteristics in broilers
      exposed to chronic heat stress, 144 male Arbor Acres broilers (28 d old) were
      randomly distributed to positive control (PC, 22 degrees C, basal diet), heat
      stress (HS, consistent 32 degrees C, basal diet), or heat stress + taurine (HS +
      T, consistent 32 degrees C, basal diet + 5.00 g/kg taurine) groups, with 6 cages
      per group and 8 birds per cage. Chronic heat stress significantly decreased body
      weight, average daily gain, and average daily feed intake, and increased cloacal
      temperature and feed conversion ratio (FCR, P < 0.05). Though taurine
      supplementation tended to decrease the FCR in the HS + T group compared with the
      HS group after 14 d of heat exposure (P = 0.071), there were no significant
      alleviative effects of taurine supplementation on the increased cloacal
      temperature and decreased growth performance in chronic heat-stressed broilers (P
      > 0.05). After 7 and 14 d of heat exposure, taurine supplementation significantly
      increased the proportion of breast muscle and hormone-sensitive lipase activity
      in the abdominal fat (P < 0.05), and decreased the mRNA expressions of muscle
      atrophy F-box protein (MAFbx) and muscle ring-finger protein-1 (MuRF1) in breast
      muscle compared with the HS group (P < 0.05). After 7 d of heat exposure, taurine
      supplementation significantly increased serum non-esterified fatty acid
      concentration (P < 0.05), and decreased the mRNA expressions of acetyl-CoA
      carboxylase 1c (ACC) and muscular isoform of carnitine palmitoyl transferase 1 (M
      CPT1) compared with the HS group (P < 0.05). In addition, the mRNA expressions of
      M-CPT1 and ribosomal protein S6 kinase, 70 kDa (p70S6K) in the HS + T group were
      significantly higher than those of the other two groups after 14 d of heat
      exposure (P < 0.05). In conclusion, taurine supplementation can improve carcass
      characteristics of chronic heat-stressed broilers by facilitating lipolysis for
      energy, enhancing protein synthesis, and suppressing protein degradation of the
      breast muscles.

PMID- 30239843
TI  - Rapid Divergence of Genome Architectures Following the Origin of an
      Ectomycorrhizal Symbiosis in the Genus Amanita.
AB  - Fungi are evolutionary shape shifters and adapt quickly to new environments.
      Ectomycorrhizal (EM) symbioses are mutualistic associations between fungi and
      plants and have evolved repeatedly and independently across the fungal tree of
      life, suggesting lineages frequently reconfigure genome content to take advantage
      of open ecological niches. To date analyses of genomic mechanisms facilitating EM
      symbioses have involved comparisons of distantly related species, but here, we
      use the genomes of three EM and two asymbiotic (AS) fungi from the genus Amanita
      as well as an AS outgroup to study genome evolution following a single origin of
      symbiosis. Our aim was to identify the defining features of EM genomes, but our
      analyses suggest no clear differentiation of genome size, gene repertoire size,
      or transposable element content between EM and AS species. Phylogenetic inference
      of gene gains and losses suggests the transition to symbiosis was dominated by
      the loss of plant cell wall decomposition genes, a confirmation of previous
      findings. However, the same dynamic defines the AS species A. inopinata,
      suggesting loss is not strictly associated with origin of symbiosis. Gene
      expansions in the common ancestor of EM Amanita were modest, but lineage specific
      and large gene family expansions are found in two of the three EM extant species.
      Even closely related EM genomes appear to share few common features. The genetic
      toolkit required for symbiosis appears already encoded in the genomes of
      saprotrophic species, and this dynamic may explain the pervasive, recurrent
      evolution of ectomycorrhizal associations.

PMID- 30239847
TI  - Enhanced Rubisco activation associated with maintenance of electron transport
      alleviates inhibition of photosynthesis under low nitrogen conditions in winter
      wheat seedlings.
AB  - Studying the response of photosynthesis to low nitrogen (N) and the underlying
      physiological mechanism can provide a theoretical basis for breeding N-efficient
      cultivars and optimizing N management. We conducted hydroponic experiments using
      two wheat (Triticum aestivum) cultivars, Zaoyangmai (low N sensitive) and
      Yangmai158 (low N tolerant), with either 0.25 mM N as a low N (LN) treatment or 5
      mM N as a control. Under LN, a decrease in net photosynthetic rate (Pn) was
      attributed to reduction in the maximum Rubisco carboxylation rate, which then
      accelerated a reduction in the maximum ribulose-1,5-bisphosphate regeneration
      rate, and the reduction in Pn was 5-35% less in Yangmai158 than in Zaoyangmai.
      Yangmai158 maintained a 10-25% higher Rubisco concentration, especially in the
      upper leaves, and up-regulated Rubisco activase activity compared with Zaoyangmai
      to increase the Rubisco activation to sustain Rubisco carboxylation under LN
      conditions. In addition, Yangmai158 increased electron flux to the
      photorespiratory carbon oxidation cycle and alternative electron flux to maintain
      a faster electron transport rate and avoid photodamage. In conclusion, the LN
      tolerant cultivar showed enhanced Rubisco activation and sustained electron
      transport to maintain a greater photosynthetic capacity under LN conditions.

PMID- 30239848
TI  - The subventricular zone concept: ready for therapeutic implications?

PMID- 30239849
TI  - Can Less Be More for Individuals With Low-Risk Breast Cancer?

PMID- 30239850
TI  - The potential usefulness of serum biomarkers in high-altitude medicine.

PMID- 30239851
TI  - Relationships between feeding behaviors and performance traits in slow-growing
      yellow broilers.
AB  - This study was conducted to investigate the feeding behaviors of slow-growing
      yellow broilers and the relationships of feeding behaviors with performance
      traits. With the help of automatic recording systems in floor houses, feeding
      events from a pure line of slow-growing yellow broilers were recorded from 57 to
      77 d of age. After data quality control, a total of 116,477 feeding records from
      319 birds were used for analyses. Feeding behaviors including number of visits
      per day (18.74), feeding duration per day (71.17 min/d), feeding duration per
      visit (262.00 s/visit), feeding rate (2.19 g/min), and feed intake per visit
      (8.52 g/visit) were calculated according to feeding records. Correlation analyses
      and comparisons between divergent efficiency groups were performed to examine the
      relationships between feed efficiency and feeding behaviors. Absolute
      correlations between residual feed intake (RFI) and feeding behaviors (except for
      feed intake per visit) were significant but weak (r = 0.18 to 0.34, P < 0.05),
      whereas feed conversion ratio (FCR) was not significantly correlated with any
      feeding behaviors. All of the weight-associated traits were positively correlated
      with feeding rate and feed intake per visit (r = 0.19 to 0.25, P < 0.05).
      Compared with the inefficient birds with the 20% highest RFI or FCR (HRFI or
      HFCR), the efficient ones with the 20% lowest RFI or FCR (LRFI or LFCR) ate
      faster (P < 0.05), spent shorter eating duration (P < 0.05) and had similar feed
      intakes per visit (P > 0.05). However, number of visits per day and the feeding
      duration per day were lower in the LRFI group than in the HRFI group (P < 0.05)
      but were not significantly different between the LFCR and HFCR groups (P > 0.05).
      In summary, this study shows the feeding behaviors of group-housed slow-growing
      yellow broilers and observed that RFI has closer relationships with feeding
      behaviors than FCR does, and the selection for birds with improved RFI may result
      in fewer visits, shorter duration and faster feeding rate.

PMID- 30239852
TI  - Potential of Co-Fumigation with Phosphine (PH3) and Sulfuryl Fluoride (SO2F2) for
      the Management of Strongly Phosphine-Resistant Insect Pests of Stored Grain.
AB  - Resistance to phosphine (PH3) in key insect pests of stored grain is increasing,
      with a requirement for maintaining a dose as high as 1 mg l-1 for 14 d for
      effective fumigation, which is difficult to achieve under most commercial storage
      conditions. There is no suitable replacement for PH3, as most of the available
      alternatives suffer from specific weaknesses, creating an urgent need to increase
      the efficacy of this fumigant. One such possibility is co-fumigation of PH3 with
      another fumigant, sulfuryl fluoride (SO2F2-SF), with the goal of decreasing the
      time required for a successful fumigation. In this study, adult of two PH3
      resistant strains in each of four key grain insect pests, Rhyzopertha dominica,
      (F.) (Coleoptera: Bostrichidae) Tribolium castaneum Herbst (Coleoptera:
      Tenebrionidae), Sitophilus oryzae (L.) (Coleoptera: Curculionidae), and
      Cryptolestes ferrugineus (Stephens) (Coleoptera: Laemophloeidae) were fumigated
      with PH3 and SF individually as well as in combinations at 25 degrees C over 48
      h. Mortality responses in each species were subjected to probit analysis to
      determine the LC50 and LC99.9 of PH3, SF, and PH3 + SF. Co-fumigation of PH3 with
      SF resulted in a 50% reduction of the PH3 concentration required to achieve 99.9%
      mortality in two pest species. For example, the PH3 + SF mixture, reduced the
      amount of PH3 required from 14.2-14.5 to 5.6-6.36 mg l-1 and from 2.71-5.03 to
      0.93-1.2 mg l-1, respectively, for C. ferrugineus and S. oryzae. The overall
      mortality response to the PH3 + SF mixture followed an "additive model"
      suggesting that mutual enhancement in toxicity can be achieved with this mixture
      specifically to control PH3-resistant insects.

PMID- 30239853
TI  - Serum and acute phase protein changes in laying hens, infested with poultry red
      mite.
AB  - The poultry red mite (PRM) is one of the most economically important
      ectoparasites of laying hens globally. This mite can have significant deleterious
      effects on its fowl host including distress, anemia, reduced egg production, and
      reduced egg quality. This study was conducted to evaluate the influence of PRM on
      the serum protein profile in laying hens and its effect on the acute phase
      proteins (APPs) to assess their potential as biomarkers for mite
      infestation.Three APPs: alpha-1 acid glycoprotein (AGP), serum amyloid-A (SAA),
      and ceruloplasmin (CP) were measured in serum samples collected from laying hens
      at 12 and 17 wk of age, and then for up to 4 mo after a challenge with PRM
      (starting at 18.5 wk of age). The serum protein profile (SDS-PAGE/nanoflow HPLC
      electrospray tandem mass spectrometry) and concentration of individual serum
      proteins (SDS-PAGE-band densitometry) were also compared.Post challenge there was
      a positive correlation (r = 0.489; P < 0.004) between the levels of SAA and the
      PRM numbers. The levels of SAA steadily increased after the PRM challenge and
      were significantly different than the pre-challenge levels at 28, 32, and 36 wk
      of age (P < 0.01). The PRM numbers also peaked around 31-33 wk of age. The
      results for AGP and CP in comparison were inconsistent. Proteomics revealed the
      presence of 2 high molecular weight proteins in the serum between 12 and 17 wk of
      age. These were identified as Apolipoprotein-B and Vitellogenin-2, and their
      increase was commensurate with the onset of lay. No other major differences were
      detected in the protein profiles of blood sera collected pre and post challenge.
      We conclude that SAA could be used as a useful biomarker to monitor PRM
      infestation in commercial poultry flocks and that PRM infestation does not
      disrupt the production of the major proteins in the serum that are associated
      with egg formation.

PMID- 30239854
TI  - Genistein increases progesterone secretion by elevating related enzymes in
      chicken granulosa cells.
AB  - Genistein, a biologically active isoflavone, exists in many soy products. It is
      well known that genistein binds to both oestrogen receptor alpha (ERalpha) and
      oestrogen receptor beta (ERbeta), but it has a higher affinity to ERbeta.
      Genistein can also bind to the G protein-coupled receptor 30 (GPR30, also known
      as G protein-coupled oestrogen receptor 1 or GPER). Furthermore, weak oestrogenic
      activity has been found in genistein, but the mechanism of action remains
      unknown. The aim of this study was to investigate the in vitro effects of
      genistein on the secretion of progesterone (P4) and oestradiol (E2) in chicken
      granulosa cells harvested from follicles, as well as the mRNA expression of ERs
      in these cells. In addition, we examined the expression of key enzymes including
      steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain
      cleavage (P450scc), and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the
      process of P4 synthesis. The results showed that genistein did not affect the
      viability of granulosa cells, nor was the proliferating cell nuclear antigen
      (PCNA) protein changed. Among the 1-, 10-, 100-, and 1,000-nM concentrations
      tested, treatment with 1 nM genistein for 48 h significantly increased P4 but did
      not affect E2 secretion. Real-time PCR results showed that the ERbeta gene
      expression in granulosa cells was markedly upregulated by 1 nM genistein
      treatment for 48 h, but there was no significant difference in ERalpha and GPR30
      expression. Genistein also increased the gene expression of StAR, P450scc and
      3beta-HSD in the cultured granulosa cells. These results indicate that genistein
      acts directly on chicken granulosa cells to increase P4 production by
      upregulating the gene expression of key enzymes through binding in ERbeta. It may
      exert positive effects on the reproduction of late-laying hens and act as an
      effective and safe feed additive for animals.

PMID- 30239855
TI  - Childhood locus of control and self-esteem, education, psychological distress and
      physical exercise as predictors of adult obesity.
AB  - Objective: To investigate to what extent locus of control, self-esteem,
      psychological distress, physical exercise, as well as socio-demographic factors
      are associated with obesity in 42-year-old adults in a longitudinal birth cohort
      study. Method: The sample consisted of 5645 participants born in Great Britain in
      1970 and followed up at 10, 34 and 42 years with data on body mass index measured
      at 34 and 42 years. Results: There was an increase of adult obesity from 15.5% at
      age 34 to 21.2% at 42 years. Locus of control and self-esteem measured at age 10
      years, psychological distress and educational qualifications assessed at age 34,
      and current occupational levels and physical exercise were all significantly
      associated with adult obesity at age 42. The associations remained significant
      after controlling for birth weight and gestation, maternal and paternal BMI,
      childhood BMI, and intelligence. Conclusion: Childhood locus of control and self
      esteem, educational qualifications, psychological distress and physical exercise
      were all significantly and independently associated with adult obesity.

PMID- 30239856
TI  - A golden age of travel: advancing the interests of older travellers.

PMID- 30239857
TI  - Comparison of Early Nasal Intermittent Positive Pressure Ventilation and Nasal
      Continuous Positive Airway Pressure in Preterm Infants with Respiratory Distress
      Syndrome.
AB  - Aims: To compare the effect of early nasal intermittent positive pressure
      ventilation (nIPPV) and nasal continuous positive airway pressure (nCPAP) in
      terms of the need for endotracheal ventilation in the treatment of respiratory
      distress syndrome (RDS) in preterm infants born between 24 and 32 gestational
      weeks. Methods: This is a randomized, controlled, prospective, single-centered
      study. Forty-two infants were randomized to nIPPV and 42 comparable infants to
      nCPAP (birth weight 1356 +/- 295 and 1359 +/- 246 g and gestational age 29.2 +/-
      1.7 and 29.4 +/- 1.5 weeks, respectively). Results: The need for endotracheal
      intubation and invasive mechanical ventilation was significantly lower in the
      nIPPV group than the nCPAP group (11.9% and 40.5%, respectively, p < 0.05). There
      were no differences in the duration of total nasal respiratory support, duration
      of invasive mechanical ventilation, bronchopulmonary dysplasia or other early
      morbidities. Conclusion: nIPPV compared with nCPAP reduced the need for
      endotracheal intubation and invasive mechanical ventilation in premature infants
      with RDS.

PMID- 30239858
TI  - Prevalence of problem drinking and associated factors in a representative German
      sample of adolescents and young adults.
AB  - Background: Alcohol use in youth is regarded as an important public health
      concern and in a recent survey in 35 European countries, every third student
      reported heavy episodic drinking. While prevalence estimates for problem drinking
      in adults from representative population samples are available, corresponding
      numbers for adolescents in Germany are currently lacking. Methods: A
      representative sample of 1531 12-25 years old in Germany was investigated with a
      standardized questionnaire concerning problem drinking (assessed with the AUDIT
      C) and psychosocial aspects (anxiety with the GAD-2, depressive symptoms with the
      PHQ-2 and smoking behavior). Due to missing values, we could calculate prevalence
      estimates, chi-square tests and logistic regression analyses for 1490 cases.
      Results: The 1-year prevalence of problem drinking in 12-25 years old in Germany
      was 18.2%. Overall, 5.0% of the adolescents (aged 12-17 years) and 27.7% of the
      young adults (aged 18-25 years) reported problem drinking in the last year. Young
      adult males more often showed problem drinking than females, while no gender
      differences in adolescents were observed. Problem drinking was associated with
      male gender, higher age, smoking behavior and depressive symptoms. Conclusions:
      According to the study findings, problem drinking is widespread in 12-25 years
      old in Germany.

PMID- 30239861
TI  - Uncommon low-grade brain tumors.
AB  - Search strategy and selection criteria: An initial search of PubMed used broad
      search terms 'brain tumors', 'low-grade', 'radiotherapy, 'chemotherapy',
      'surgery' and 'treatment' from January 1990 to March 2018. A subsequent focused
      search was undertaken using the names of individual histological subtypes of low
      grade brain tumors as in the 2016 WHO classification. Only papers published in
      English were reviewed. The final reference list was generated on the basis of
      originality and relevance to the broad scope of this review.

PMID- 30239859
TI  - Transcriptional landscape changes during human embryonic stem cell derivation.
AB  - STUDY QUESTION: What are the transcriptional changes occurring during the human
      embryonic stem cell (hESC) derivation process, from the inner cell mass (ICM) to
      post-ICM intermediate stage (PICMI) to hESC stage, that have downstream effects
      on pluripotency states and differentiation? SUMMARY ANSWER: We reveal that
      although the PICMI is transcriptionally similar to the hESC profile and distinct
      from ICM, it exhibits upregulation of primordial germ cell (PGC) markers,
      dependence on leukemia inhibitory factor (LIF) signaling, upregulation of naive
      pluripotency-specific signaling networks and appears to be an intermediate
      switching point from naive to primed pluripotency. WHAT IS KNOWN ALREADY: It is
      currently known that the PICMI exhibits markers of early and late-epiblast stage.
      It is suggested that hESCs acquire primed pluripotency features due to the
      upregulation of post-implantation genes in the PICMI which renders them
      predisposed towards differentiation cues. Despite this current knowledge, the
      transcriptional landscape changes during hESC derivation from ICM to hESC and the
      effect of PICMI on pluripotent state is still not well defined. STUDY DESIGN,
      SIZE, DURATION: To gain insight into the signaling mechanisms that may govern the
      ICM to PICMI to hESC transition, comparative RNA sequencing (RNA-seq) analysis
      was performed on preimplantation ICMs, PICMIs and hESCs in biological and
      technical triplicates (n = 3). PARTICIPANTS/MATERIALS, SETTING, AND METHODS:
      Primed hESCs (XX) were maintained in feeder-free culture conditions on Matrigel
      for two passages and approximately 50 cells were collected in biological and
      technical triplicates (n = 3). For ICM sample collection, Day 3, frozen-thawed
      human embryos were cultured up to day five blastocyst stage and only good quality
      blastocysts were subjected to laser-assisted micromanipulation for ICM collection
      (n = 3). Next, day six expanded blastocysts were cultured on mouse embryonic
      fibroblasts and manual dissection was performed on the PICMI outgrowths between
      post-plating Day 6 and Day 10 (n = 3). Sequencing of these samples was performed
      on NextSeq500 and statistical analysis was performed using edgeR (false discovery
      rate (FDR) < 0.05). MAIN RESULTS AND THE ROLE OF CHANCE: Comparative RNA-seq data
      analysis revealed that 634 and 560 protein-coding genes were significantly up and
      downregulated in hESCs compared to ICM (FDR < 0.05), respectively. Upon ICM to
      PICMI transition, 471 genes were expressed significantly higher in the PICMI
      compared to ICM, while 296 genes were elevated in the ICM alone (FDR < 0.05).
      Principle component analysis showed that the ICM was completely distinct from the
      PICMI and hESCs while the latter two clustered in close proximity to each other.
      Increased expression of E-CADHERIN1 (CDH1) in ICM and intermediate levels in the
      PICMI was observed, while CDH2 was higher in hESCs, suggesting a role of
      extracellular matrix components in facilitating pluripotency transition during
      hESC derivation. The PICMI also showed regulation of naive-specific LIF and bone
      morphogenetic protein signaling, differential regulation of primed pluripotency
      specific fibroblast growth factor and NODAL signaling pathway components,
      upregulation of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of
      rapamycin (mTOR) pathway (PI3K/AKT/mTORC), as well as predisposition towards the
      germ cell lineage, further confirmed by gene ontology analysis. Hence, the data
      suggest that the PICMI may serve as an intermediate pluripotency stage which,
      when subjected to an appropriate culture niche, could aid in enhancing naive hESC
      derivation and germ cell differentiation efficiency. LARGE-SCALE DATA: Gene
      Expression Omnibus (GEO) Accession number GSE119378. LIMITATIONS, REASONS FOR
      CAUTION: Owing to the limitation in sample availability, the sex of ICM and PICMI
      have not been taken into consideration. Obtaining cells from the ICM and
      maintaining them in culture is not feasible as it will hamper the formation of
      PICMI and hESC derivation. Single-cell quantitative real-time PCR on low ICM and
      PICMI cell numbers, although challenging due to limited availability of human
      embryos, will be advantageous to further corroborate the RNA-seq data on
      transcriptional changes during hESC derivation process. WIDER IMPLICATIONS OF THE
      FINDINGS: We elucidate the dynamics of transcriptional network changes from the
      naive ICM to the intermediate PICMI stage and finally the primed hESC lines. We
      provide an in-depth understanding of the PICMI and its role in conferring the
      type of pluripotent state which may have important downstream effects on
      differentiation, specifically towards the PGC lineage. This knowledge contributes
      to our limited understanding of the true nature of the human pluripotent state in
      vitro. STUDY FUNDING/COMPETING INTEREST(S): This research is supported by the
      Concerted Research Actions funding from Bijzonder Onderzoeksfonds University
      Ghent (BOF GOA 01G01112).The authors declare no conflict of interest.

PMID- 30239862
TI  - Autonomous Trajectory Planning for External Ventricular Drain Placement.
AB  - BACKGROUND: External ventricular drain (EVD) placement is the most frequently
      performed neurosurgical procedure for management of various conditions including
      hydrocephalus, traumatic brain injury, and stroke. State-of-the-art computational
      pattern recognition techniques could improve the safety and accuracy of EVD
      placement. Placement of the Kocher's point EVD is the most common neurosurgical
      procedure which is often performed in urgent conditions. OBJECTIVE: To present
      the development of a novel computer algorithm identifying appropriate anatomy and
      autonomously plan EVD placement on clinical computed tomography (CT) scans.
      METHODS: The algorithm was tested on 2 data sets containing 5-mm slice
      noncontrast CT scans. The first contained images of 300 patients without
      significant intracranial pathology (normal), the second of 43 patients with
      significant acute intracranial hemorrhage. Automated planning was performed by
      custom 2-tiered heuristic with run-time template selection in combination with
      refinement using nonlinear image registration. RESULTS: Automated EVD planning
      was accurate in 297 of 300 normal and 41 of 43 patient cases. In the normal data
      set, mean distance between Kocher's point and the ipsilateral foramen of Monro
      was 63 +/- 3.1 mm in women and 65 +/- 6.5 mm in men (P = .0008). Trajectory angle
      with respect to the sagittal plane was 91 +/- 6 degrees  in women and 90 +/- 6
      degrees  in men (obtuse posterior) (P = .15); to the coronal plane, 85 +/- 6
      degrees  and 86 +/- 5 degrees  in women and men (P = .12), respectively (acute
      lateral). CONCLUSION: A combination of linear and nonlinear image registration
      techniques accurately planned EVD trajectory in 99% of normal scans and 95% of
      scans with significant intracranial hemorrhage.

PMID- 30239863
TI  - Improvement in pain interference after palliative radiotherapy for solid and
      hematologic painful tumors: a secondary analysis of a prospective observational
      study.
AB  - Background: We previously demonstrated that patients with painful hematologic
      tumors were more likely to experience pain response after palliative radiotherapy
      (RT) than those with painful solid tumors. However, it is unknown whether change
      in pain interference differs between these two tumor types. In the present study,
      we carried out a secondary analysis of our previous prospective observational
      study to investigate this matter. Methods: From patients undergoing palliative RT
      to treat painful tumors, Brief Pain Inventory data were collected at the start of
      RT and at the 1-, 2-, and 3- month follow-ups. The Mann-Whitney U test was used
      to compare changes in pain interference score from baseline between the two
      groups. Results: Of the 237 patients, 203 (86%) had solid and 34 (14%) had
      hematologic index tumors planned to receive RT. At baseline, the groups did not
      differ significantly in terms of pain score, analgesic use, or pain interference
      score. At the 1-, 2-, and 3-month follow-ups, the changes in pain interference
      score from baseline did not differ significantly between the two groups. In both
      groups, all seven pain interference items, other than sleep in patients with
      hematologic tumors at the 2-month follow-up, were significantly improved (P <
      0.05). Conclusions: The two groups showed comparable benefit from RT in terms of
      improvement in pain interference. Patients with tumor-related pain should be
      offered the option of palliative RT, irrespective of whether the painful tumor is
      solid or hematologic.

PMID- 30239864
TI  - Radiation dosimetry and repair kinetics of DNA damage foci in mouse pachytene
      spermatocyte and round spermatid stages.
AB  - Accurate quantification of DNA double strand breaks (DSB) in testicular germ
      cells is difficult because of cellular heterogeneity and the presence of
      endogenous gammaH2AX. Here, we used confocal microscopy to quantify DNA damage
      and repair kinetics following gamma-irradiation (0.5-4 Gy) in three major mouse
      male germ cell stages, early and late pachytene spermatocytes and round
      spermatids (RSs), following a defined post irradiation time course. Dose-response
      curves showing linear best fit validated gammaH2AX focus as a rapid biodosimetric
      tool in these substages in response to whole body in vivo exposure. Stage
      specific foci yield/dose and repair kinetics demonstrated differential
      radiosensitivity and repair efficiency: early pachytenes (EP) repaired most
      rapidly and completely followed by late pachytene (LP) and RSs. Repair kinetics
      for all three stages followed 'exponential decay' in response to each radiation
      dose. In pachytenes immediate colocalisation of gammaH2AX and 53BP1, which
      participates in non-homologous end-joining repair pathway, was followed by
      dissociation from the major focal area of gammaH2AX by 4 h demonstrating ongoing
      DSB repair. These results confirm the differential radiosensitivity and repair
      kinetics of DSBs in male germ cells at different stages. Taken together, our
      results provide a simple and accurate method for assessing DNA damage and repair
      kinetics during spermatogenesis.

PMID- 30239865
TI  - Chemotherapy-induced genotoxic damage to bone marrow cells: long-term
      implications.
AB  - Mesenchymal stem/stromal cells (MSCs) within the bone marrow (BM) are vitally
      important in forming the micro-environment supporting haematopoiesis after
      myeloablative chemotherapy. MSCs are known to be damaged phenotypically and
      functionally by chemotherapy; however, to the best our knowledge, the persistence
      of genotoxic effects of chemotherapy on the BM micro-environment has not been
      studied. We therefore aimed to evaluate genotoxic effects of chemotherapy on the
      BM both in vitro and in vivo, using the comet and micronucleus assays, focussing
      on the persistence of DNA lesions that may contribute to complications in the
      patient. The MSC cell line (HS-5) and primary cord blood mononuclear cells
      (CBMNCs: a source of undamaged DNA) were exposed to the chemotherapeutic agent
      cyclophosphamide (CY) within a physiologically relevant in vitro model. CY
      treatment resulted in significant increases in CBMNC DNA damage at all time
      points tested (3-48 h exposure). Similarly, HS-5 cells exposed to CY exhibited
      significant increases in DNA damage as measured by the comet assay, with
      increased numbers of abnormal cells visible in the micronucleus assay. In
      addition, even 48 h after removal of 48-h CY treatment, DNA damage remains
      significantly increased in treated cells relative to controls. In patients
      treated with chemotherapy for haematological malignancy, highly significant
      increases in damaged DNA were seen in BM cells isolated from one individual 1
      year after completion of therapy for acute leukaemia compared with pretreatment
      (P < 0.001). Similarly, two individuals treated 7 and 17 years previously with
      chemotherapy exhibited significant increases of damaged DNA in MSC compared with
      untreated age- and sex-matched controls (P < 0.05). Unlike haematopoietic cells,
      MSCs are not replaced following a stem cell transplant. Therefore, long-term
      damage to MSC may impact on engraftment of either allogeneic or autologous
      transplants. In addition, persistence of DNA lesions may lead to genetic
      instability, correlating with the significant number of chemotherapy-treated
      individuals who have therapy-related malignancies.

PMID- 30239866
TI  - Serum Nitrogen and Carbon Stable Isotope Ratios Meet Biomarker Criteria for Fish
      and Animal Protein Intake in a Controlled Feeding Study of a Women's Health
      Initiative Cohort.
AB  - Background: Natural abundance stable isotope ratios are candidate biomarkers of
      dietary intake that have not been evaluated in a controlled feeding study in a US
      population. Objectives: Our goals were to evaluate dietary associations with
      serum carbon (CIR), nitrogen (NIR), and sulfur (SIR) isotope ratios in
      postmenopausal women, and to evaluate whether statistical models of dietary
      intake that include multiple isotopes and participant characteristics meet
      criteria for biomarker evaluation. Methods: Postmenopausal women from the Women's
      Health Initiative (n = 153) were provided a 2-wk controlled diet that
      approximated each individual's habitual food intake. Dietary intakes of animal
      protein, fish/seafood, red meat, poultry, egg, dairy, total sugars, added sugars,
      sugar-sweetened beverages (SSBs), and corn products were characterized during the
      feeding period with the use of the Nutrition Data System for Research (NDS-R).
      The CIR, NIR, and SIR were measured in sera collected from fasting women at the
      beginning and the end of the feeding period. Linear models based on stable
      isotope ratios and participant characteristics predicted dietary intake. The
      criterion used for biomarker evaluation was R2 >= 0.36, based on the study's
      power to detect true associations with R2 >= 0.50. Results: The NIR was
      associated with fish/seafood intake and met the criterion for biomarker
      evaluation (R2 = 0.40). The CIR was moderately associated with intakes of red
      meat and eggs, but not to the criterion for biomarker evaluation, and was not
      associated with intake of sugars (total, added, or SSB). A model of animal
      protein intake based on the NIR, CIR, and participant characteristics met the
      criterion for biomarker evaluation (R2 = 0.40). Otherwise, multiple isotopes did
      not improve models of intake, and improvements from including participant
      characteristics were modest. Conclusion: Serum stable isotope ratios can, with
      participant characteristics, meet biomarker criteria as measures of fish/seafood
      and animal protein intake in a sample of postmenopausal women. This trial was
      registered at clinicaltrials.gov as NCT00000611.

PMID- 30239868
TI  - Full Bayesian Comparative Phylogeography from Genomic Data.
AB  - A challenge to understanding biological diversification is accounting for
      community-scale processes that cause multiple, co-distributed lineages to co
      speciate. Such processes predict non-independent, temporally clustered
      divergences across taxa. Approximate-likelihood Bayesian computation (ABC)
      approaches to inferring such patterns from comparative genetic data are very
      sensitive to prior assumptions and often biased toward estimating shared
      divergences. We introduce a full-likelihood Bayesian approach, ecoevolity, which
      takes full advantage of information in genomic data. By analytically integrating
      over gene trees, we are able to directly calculate the likelihood of the
      population history from genomic data, and efficiently sample the model-averaged
      posterior via Markov chain Monte Carlo algorithms. Using simulations, we find
      that the new method is much more accurate and precise at estimating the number
      and timing of divergence events across pairs of populations than existing
      approximate-likelihood methods. Our full Bayesian approach also requires several
      orders of magnitude less computational time than existing ABC approaches. We find
      that despite assuming unlinked characters (e.g., unlinked single-nucleotide
      polymorphisms), the new method performs better if this assumption is violated in
      order to retain the constant characters of whole linked loci. In fact, retaining
      constant characters allows the new method to robustly estimate the correct number
      of divergence events with high posterior probability in the face of character
      acquisition biases, which commonly plague loci assembled from reduced
      representation genomic libraries. We apply our method to genomic data from four
      pairs of insular populations of Gekko lizards from the Philippines that are not
      expected to have co-diverged. Despite all four pairs diverging very recently, our
      method strongly supports that they diverged independently, and these results are
      robust to very disparate prior assumptions.

PMID- 30239869
TI  - Population description and clinical response assessment for spinal metastases:
      the SPINO group report.

PMID- 30239867
TI  - Molecular mechanisms for dynamic regulation of N1 riboswitch by aminoglycosides.
AB  - A synthetic riboswitch N1, inserted into the 5'-untranslated mRNA region of
      yeast, regulates gene expression upon binding ribostamycin and neomycin.
      Interestingly, a similar aminoglycoside, paromomycin, differing from neomycin by
      only one substituent (amino versus hydroxyl), also binds to the N1 riboswitch,
      but without affecting gene expression, despite NMR evidence that the N1
      riboswitch binds all aminoglycosides in a similar way. Here, to explore the
      details of structural dynamics of the aminoglycoside-N1 riboswitch complexes, we
      applied all-atom molecular dynamics (MD) and temperature replica-exchange MD
      simulations in explicit solvent. Indeed, we found that ribostamycin and neomycin
      affect riboswitch dynamics similarly but paromomycin allows for more flexibility
      because its complex lacks the contact between the distinctive 6' hydroxyl group
      and the G9 phosphate. Instead, a transient hydrogen bond of 6'-OH with A17 is
      formed, which partially diminishes interactions between the bulge and apical loop
      of the riboswitch, likely contributing to riboswitch inactivity. In many ways,
      the paromomycin complex mimics the conformations, interactions, and Na+
      distribution of the free riboswitch. The MD-derived interaction network helps
      understand why riboswitch activity depends on aminoglycoside type, whereas for
      another aminoglycoside-binding site, aminoacyl-tRNA site in 16S rRNA, activity is
      not discriminatory.

PMID- 30239871
TI  - Introduction of a New Interactive Paradigm to Define the Next Generation of
      Visualization in Neurosurgical Anatomy.

PMID- 30239872
TI  - Operative Anatomy of the Human Skull: A Virtual Reality Expedition.
AB  - INTRODUCTION: The human cranial vault possesses an incredible, complex anatomical
      intricacy. Bridging the divide between 2-dimensional (2D) learning resources and
      the 3-dimensional (3D) world in which the anatomy becomes clinically relevant
      poses an intellectual challenge. Advances in computer graphics and modelling
      technologies have allowed increasingly accurate and representative resources to
      supplement cadaveric dissection specimens. OBJECTIVE: To create accurate virtual
      models of all cranial bones to augment education, research, and clinical
      endeavours. METHODS: Through a careful analysis of osteological specimens and
      high-resolution radiographic studies, a highly accurate virtual model of the
      human skull was created and annotated with relevant anatomical landmarks.
      RESULTS: The skull was divided into 6 major segments including frontal, ethmoid,
      sphenoid, temporal, parietal, and occipital bones. These bones were thoroughly
      annotated to demonstrate the intricate anatomical features. CONCLUSION: This
      virtual model has the potential to serve as a valuable resource for educational,
      research, and clinical endeavours, and demonstrates the significance of advances
      in computer modelling that can contribute to our understanding of neurosurgical
      anatomical substrates.

PMID- 30239873
TI  - Effects of diets with different energy and bile acids levels on growth
      performance and lipid metabolism in broilers.
AB  - This experiment was conducted to evaluate the effects of bile acids (BAs) on the
      growth performance and lipid metabolism of broilers fed with different energy
      level diets. 480 one-day-old Arbor Acres broilers (45.01 +/- 0.26 g) were
      allotted to a 2 * 2 factorial design with 2 levels of energy (basal or high
      energy level) and 2 levels of BAs (with or without BAs supplementation),
      resulting in 4 groups of 8 replicates; the experiment lasted 42 d. High-energy
      diets decreased the feed/gain ratio (F/G) from 1 to 21 d (P < 0.05), and
      increased the liver index and abdominal fat percentage at 42 d (P < 0.05). The
      serum total triglyceride (TG) and high-density lipoprotein cholesterol at 42 d
      were increased by high-energy diets (P < 0.05), while the hepatic lipoprotein
      lipase (LPL) activity at 21 and 42 d was decreased (P < 0.05). BAs
      supplementation increased the body weight at 21 d and decreased the F/G during
      entire period (P < 0.05), as well as improved the carcass quality reflected by
      decreased abdominal fat percentage at 42 d and increased breast muscle percentage
      at 21 and 42 d (P < 0.05). The serum TG at 21 and 42 d were decreased by BAs (P <
      0.05), and the hepatic LPL activity at 42 d was increased (P < 0.05). In
      addition, high-energy diets increased the expression of sterol regulatory element
      binding transcription factor 1, acetyl-CoA carboxylase, and fatty acid synthase
      (P < 0.05), while BAs diets decreased these genes expression (P < 0.05).
      Moreover, BAs supplementation also increased the expression of carnitine
      palmitoyltransferase 1 (P < 0.05), which was increased in high-energy groups (P <
      0.05). In conclusion, BAs supplementation could increase growth performance,
      elevate carcass quality, and improve lipid metabolism in broilers.

PMID- 30239874
TI  - Arabidopsis HD-Zip II proteins regulate the exit from proliferation during leaf
      development in canopy shade.
AB  - The shade avoidance response is mainly evident as increased plant elongation at
      the expense of leaf and root expansion. Despite the advances in understanding the
      mechanisms underlying shade-induced hypocotyl elongation, little is known about
      the responses to simulated shade in organs other than the hypocotyl. In
      Arabidopsis, there is evidence that shade rapidly and transiently reduces the
      frequency of cell division in young first and second leaf primordia through a non
      cell-autonomous mechanism. However, the effects of canopy shade on leaf
      development are likely to be complex and need to be further investigated. Using
      combined methods of genetics, cell biology, and molecular biology, we uncovered
      an effect of prolonged canopy shade on leaf development. We show that persistent
      shade determines early exit from proliferation in the first and second leaves of
      Arabidopsis. Furthermore, we demonstrate that the early exit from proliferation
      in the first and second leaves under simulated shade depends at least in part on
      the action of the Homeodomain-leucine zipper II (HD-Zip II) transcription factors
      ARABIDOPSIS THALIANA HOMEOBOX2 (ATHB2) and ATHB4. Finally, we provide evidence
      that the ATHB2 and ATHB4 proteins work in concert. Together the data contribute
      new insights on the mechanisms controlling leaf development under canopy shade.

PMID- 30239875
TI  - Erratum.

PMID- 30239877
TI  - PRELIMINARY RESULTS OF THE ICIDOSE 2017 INTERNATIONAL INTER-COMPARISON ON
      INTERNAL DOSE ASSESSMENT.

PMID- 30239878
TI  - Attenuated Post-Movement Beta Rebound Associated With Schizotypal Features in
      Healthy People.
AB  - Introduction: Schizophrenia and schizotypal personality disorder (SPD) lie on a
      single spectrum of mental illness and converging evidence suggests similarities
      in the etiology of the 2 conditions. However, schizotypy is a heterogeneous facet
      of personality in the healthy population and so may be seen as a bridge between
      health and mental illness. Neural evidence for such a continuity would have
      implications for the characterization and treatment of schizophrenia. Based on
      our previous work identifying a relationship between symptomology in
      schizophrenia and abnormal movement-induced electrophysiological response (the
      post-movement beta rebound [PMBR]), we predicted that if subclinical schizotypy
      arises from similar neural mechanisms to schizophrenia, schizotypy in healthy
      individuals would be associated with reduced PMBR. Methods: One-hundred sixteen
      participants completed a visuomotor task while their neural activity was recorded
      by magnetoencephalography. Partial correlations were computed between a measure
      of PMBR extracted from left primary motor cortex and scores on the Schizotypal
      Personality Questionnaire (SPQ), a self-report measure of schizotypal
      personality. Correlations between PMBR and SPQ factor scores measuring cognitive
      perceptual, interpersonal and disorganization dimensions of schizotypy were also
      computed. Effects of site, age, and sex were controlled for. Results: We found a
      significant negative correlation between total SPQ score and PMBR. This was most
      strongly mediated by variance shared between interpersonal and disorganization
      factor scores. Conclusion: These findings indicate a continuum of neural deficit
      between schizotypy and schizophrenia, with diminution of PMBR, previously
      reported in schizophrenia, also measurable in individuals with schizotypal
      features, particularly disorganization and impaired interpersonal relations.

PMID- 30239876
TI  - A Type III-B Cmr effector complex catalyzes the synthesis of cyclic
      oligoadenylate second messengers by cooperative substrate binding.
AB  - Recently, Type III-A CRISPR-Cas systems were found to catalyze the synthesis of
      cyclic oligoadenylates (cOAs), a second messenger that specifically activates
      Csm6, a Cas accessory RNase and confers antiviral defense in bacteria. To test if
      III-B CRISPR-Cas systems could mediate a similar CRISPR signaling pathway, the
      Sulfolobus islandicus Cmr-alpha ribonucleoprotein complex (Cmr-alpha-RNP) was
      purified from the native host and tested for cOA synthesis. We found that the
      system showed a robust production of cyclic tetra-adenylate (c-A4), and that c-A4
      functions as a second messenger to activate the III-B-associated RNase Csx1 by
      binding to its CRISPR-associated Rossmann Fold domain. Investigation of the
      kinetics of cOA synthesis revealed that Cmr-alpha-RNP displayed positively
      cooperative binding to the adenosine triphosphate (ATP) substrate. Furthermore,
      mutagenesis of conserved domains in Cmr2alpha confirmed that, while Palm 2 hosts
      the active site of cOA synthesis, Palm 1 domain serves as the primary site in the
      enzyme-substrate interaction. Together, our data suggest that the two Palm
      domains cooperatively interact with ATP molecules to achieve a robust cOA
      synthesis by the III-B CRISPR-Cas system.

PMID- 30239879
TI  - Trips-Viz: a transcriptome browser for exploring Ribo-Seq data.
AB  - Ribosome profiling (Ribo-Seq) is a technique that allows for the isolation and
      sequencing of mRNA fragments protected from nuclease digestion by actively
      translating ribosomes. Mapping these ribosome footprints to a genome or
      transcriptome generates quantitative information on translated regions. To
      provide access to publicly available ribosome profiling data in the context of
      transcriptomes we developed Trips-Viz (transcriptome-wide information on protein
      synthesis-visualized). Trips-Viz provides a large range of graphical tools for
      exploring global properties of translatomes and of individual transcripts. It
      enables analysis of aligned footprints to evaluate datasets quality, differential
      gene expression detection, visual identification of upstream ORFs and alternative
      proteoforms. Trips-Viz is available at https://trips.ucc.ie.

PMID- 30239880
TI  - DEVELOPMENT AND APPLICATION OF SOLID FORMS OF CaSO4:Dy THERMOLUMINESCENT
      DOSEMETERS IN RADIATION PROTECTION DOSIMETRY-A REVIEW.
AB  - CaSO4:Dy is a reliable high-sensitive themoluminescent phosphor useful for low
      level and high-level radiation measurements as it exhibits fading free linear
      dose response with a single glow peak at ~230 degrees C in these dose regions.
      For large-scale radiation protection dosimetry service, it is embedded in Teflon
      matrix with varying thicknesses. Extensive studies have been carried out with
      such CaSO4:Dy Teflon discs in individual and environmental radiation monitoring
      applications including its capability to measure International Commission on
      Radiation Units and Measurements operational quantities. The review highlights
      their development and application in high-energy photon measurements, thin wafers
      and graphite-loaded Teflon discs for beta-dosimetry, phosphor-filled aluminium
      discs for high-dose applications, 6LiF-mixed CaSO4:Dy Teflon discs for thermal
      and albedo or moderated fast neutrons, sulphur-mixed CaSO4:Dy pellets for fast
      neutron exposure even in the presence of gamma-rays and polyethylene-mixed
      CaSO4:Dy discs for fast neutrons.

PMID- 30239881
TI  - Induction of in vivo Pig-a gene mutation but not micronuclei by 5-(2-chloroethyl)
      2'-deoxyuridine, an antiviral pyrimidine nucleoside analogue.
AB  - 5-(2-Chloroethyl)-2'-deoxyuridine (CEDU) was developed as an antiviral drug. It
      has been studied in a number of in vitro and in vivo genotoxicity assays and is
      considered an unusual nucleoside analogue owing to its potent mutagenic
      potential, with little to no measurable clastogenic activity. Given this atypical
      profile, CEDU represented an interesting compound for evaluating the in vivo Pig
      a gene mutation assay, a test that is undergoing extensive validation for
      regulatory safety applications. The current report describes two studies with 7
      week-old male Wistar Han rats, one that exposed animals to several dose levels of
      CEDU for 5 consecutive days, the other for 28 consecutive days. Blood samples
      were collected at several time points and analysed for Pig-a mutant cell
      frequencies via flow cytometry. These Pig-a analyses were accompanied by
      micronucleated reticulocyte (MN-RET) measurements performed with blood samples
      collected 1 day after cessation of treatment. Both studies showed robust CEDU
      dose-related increases in Pig-a mutant reticulocytes and mutant erythrocytes.
      Conversely, neither experiment showed evidence of a CEDU-related MN-RET-inducing
      effect. These rat haematopoietic cell results were in good agreement with those
      of earlier mouse studies where in vivo mutagenesis was observed, without
      clastogenicity/aneuploidy. Taken together, these data add further support to the
      concept that the Pig-a assay represents an important complement to the widely
      used in vivo micronucleus assay, as it expands the range of important DNA lesions
      that can be detected in short-term as well as protracted exposure study designs.

PMID- 30239882
TI  - Mb- and FnCpf1 nucleases are active in mammalian cells: activities and PAM
      preferences of four wild-type Cpf1 nucleases and of their altered PAM specificity
      variants.
AB  - Cpf1s, the RNA-guided nucleases of the class II clustered regularly interspaced
      short palindromic repeats system require a short motive called protospacer
      adjacent motif (PAM) to be present next to the targeted sequence for their
      activity. The TTTV PAM sequence of As- and LbCpf1 nucleases is relatively rare in
      the genome of higher eukaryotic organisms. Here, we show that two other Cpf1
      nucleases, Fn- and MbCpf1, which have been reported to utilize a shorter, more
      frequently occurring PAM sequence (TTN) when tested in vitro, carry out efficient
      genome modification in mammalian cells. We found that all four Cpf1 nucleases
      showed similar activities and TTTV PAM preferences. Our approach also revealed
      that besides their activities their PAM preferences are also target dependent. To
      increase the number of the available targets for Fn- and MbCpf1 we generated
      their RVR and RR mutants with altered PAM specificity and compared them to the
      wild-type and analogous As- and LbCpf1 variants. The mutants gained new PAM
      specificities but retained their activity on targets with TTTV PAMs, redefining
      RR-Cpf1's PAM-specificities as TTYV/TCCV, respectively. These variants may become
      versatile substitutes for wild-type Cpf1s by providing an expanded range of
      targets for genome engineering applications.

PMID- 30239885
TI  - Salicylic acid-induced transcriptional reprogramming by the HAC-NPR1-TGA histone
      acetyltransferase complex in Arabidopsis.
AB  - Plant immunity depends on massive expression of pathogenesis-related genes (PRs)
      whose transcription is de-repressed by pathogen-induced signals. Salicylic acid
      (SA) acts as a major signaling molecule in plant immunity and systemic acquired
      resistance triggered by bacterial or viral pathogens. SA signal results in the
      activation of the master immune regulator, Nonexpressor of pathogenesis-related
      genes 1 (NPR1), which is thought to be recruited by transcription factors such as
      TGAs to numerous downstream PRs. Despite its key role in SA-triggered immunity,
      the biochemical nature of the transcriptional coactivator function of NPR1 and
      the massive transcriptional reprogramming induced by it remain obscure. Here we
      demonstrate that the CBP/p300-family histone acetyltransferases, HACs and NPR1
      are both essential to develop SA-triggered immunity and PR induction. Indeed HACs
      and NPR1 form a coactivator complex and are recruited to PR chromatin through
      TGAs upon SA signal, and finally the HAC-NPR1-TGA complex activates PR
      transcription by histone acetylation-mediated epigenetic reprogramming. Thus, our
      study reveals a molecular mechanism of NPR1-mediated transcriptional
      reprogramming and a key epigenetic aspect of the central immune system in plants.

PMID- 30239886
TI  - Pathogenicity and complete genome sequence of a fowl adenovirus serotype 8b
      isolate from China.
AB  - In this study, we determined and analyzed the complete nucleotide sequence of the
      genome of a fowl adenovirus isolate SD1356 in China and examined its
      pathogenicity in specific pathogen-free chick embryos and newly hatched chicks.
      The full genome of SD1356 was 44,454 nucleotides in length with 58.1% G + C
      content. Sequence alignment and phylogenetic analysis revealed that strain SD1356
      was clustered together belonging to serotype 8b of fowl adenoviruses E species
      (FAdV-8b). No regions homologous to early regions E1, E3, and E4 of
      mastadenoviruses were recognized, and being very similar to the typical
      organization of FAdV-E genomes. All infected embryos died 4-6 d post-inoculation
      with visible lesions, such as hyperemic, stunting, and clubbed down, etc.
      Additionally, adenovirus was found in tissues or cloacal swabs of all infected
      birds and most of the contact uninfected controls, despite lack of clinical signs
      and pathological changes. Together, our study describes the genomic
      characteristics of an FAdV-8b strain isolated in China. The reported FAdV-8b
      strain SD1356 is fetal to chick embryos and possesses horizontal transmission
      capacity in chickens.

PMID- 30239887
TI  - Cisplatin Every 3 Weeks Versus Weekly With Definitive Concurrent Radiotherapy for
      Squamous Cell Carcinoma of the Head and Neck.
AB  - Background: Concurrent chemoradiotherapy is an established component of the
      nonoperative management of locally advanced head and neck squamous cell carcinoma
      (HNSCC), but the standard dose of 100 mg/m2 cisplatin every 3 weeks is associated
      with clinically significant toxicity. Interest in a more tolerable regimen has
      led to the widespread use of weekly lower dose cisplatin, but few randomized
      trials have compared these approaches. Methods: We examined outcomes of patients
      with stage III-IVb HNSCC treated with definitive intent chemoradiotherapy using
      either high-dose cisplatin (HDC) or low-dose cisplatin (LDC), using population
      based Veterans Affairs data. In an intent-to-treat analysis, patients were
      assigned to the HDC vs LDC group according to the dose of their first cycle.
      Variables potentially influencing treatment decisions including cancer site,
      stage, smoking/alcohol use, and comorbidities were used to generate propensity
      scores (PS) for the use of HDC. We compared overall survival (OS) by treatment
      group using Cox regression, adjusting for PS. We then determined the risk of
      toxicities using PS-adjusted logistic regression. Results: A total of 2901
      patients were included in the analysis; 2200 received HDC (mean initial dose 100
      mg/m2). The mean initial dose of LDC was 40 mg/m2. After PS adjustment, HDC was
      not associated with improved OS over LDC (hazard ratio = 0.94, 95% confidence
      interval = 0.80 to 1.04). Adjusting for PS, HDC was associated with an increased
      risk of acute kidney injury, neutropenia, dehydration/electrolyte disturbance,
      and hearing loss. Conclusion: In this large, population-based study of US
      military veterans, LDC was associated with similar survival to HDC in the
      nonoperative definitive management of locally advanced HNSCC of the oral cavity,
      oropharynx, and hypopharynx/larynx. HDC was associated with statistically
      significantly more toxicity than LDC. Adoption of LDC may reduce toxicity burden
      while maintaining OS.

PMID- 30239883
TI  - The sequence features that define efficient and specific hAGO2-dependent miRNA
      silencing guides.
AB  - MicroRNAs (miRNAs) are ribonucleic acids (RNAs) of ~21 nucleotides that interfere
      with the translation of messenger RNAs (mRNAs) and play significant roles in
      development and diseases. In bilaterian animals, the specificity of miRNA
      targeting is determined by sequence complementarity involving the seed. However,
      the role of the remaining nucleotides (non-seed) is only vaguely defined,
      impacting negatively on our ability to efficiently use miRNAs exogenously to
      control gene expression. Here, using reporter assays, we deciphered the role of
      the base pairs formed between the non-seed region and target mRNA. We used
      molecular modeling to reveal that this mechanism corresponds to the formation of
      base pairs mediated by ordered motions of the miRNA-induced silencing complex.
      Subsequently, we developed an algorithm based on this distinctive recognition to
      predict from sequence the levels of mRNA downregulation with high accuracy (r2 >
      0.5, P-value < 10-12). Overall, our discovery improves the design of miRNA-guide
      sequences used to simultaneously downregulate the expression of multiple
      predetermined target genes.

PMID- 30239884
TI  - The signature motif of the Saccharomyces cerevisiae Pif1 DNA helicase is
      essential in vivo for mitochondrial and nuclear functions and in vitro for ATPase
      activity.
AB  - Pif1 family DNA helicases are conserved from bacteria to humans and have critical
      and diverse functions in vivo that promote genome integrity. Pif1 family
      helicases share a 23 amino acid region, called the Pif1 signature motif (SM) that
      is unique to this family. To determine the importance of the SM, we did
      mutational and functional analysis of the SM from the Saccharomyces cerevisiae
      Pif1 (ScPif1). The mutations deleted portions of the SM, made one or multiple
      single amino acid changes in the SM, replaced the SM with its counterpart from a
      bacterial Pif1 family helicase and substituted an alpha-helical domain from
      another helicase for the part of the SM that forms an alpha helix. Mutants were
      tested for maintenance of mitochondrial DNA, inhibition of telomerase at
      telomeres and double strand breaks, and promotion of Okazaki fragment maturation.
      Although certain single amino acid changes in the SM can be tolerated, the
      presence and sequence of the ScPif1 SM were essential for all tested in vivo
      functions. Consistent with the in vivo analyses, in vitro studies showed that the
      presence and sequence of the ScPif1 SM were critical for ATPase activity but not
      substrate binding.

PMID- 30239888
TI  - Molecular characteristics of extended-spectrum and plasmid-mediated AmpC beta
      lactamase-producing Escherichia coli isolated from commercial layer in Korea.
AB  - In the poultry industry, commercial layer farms play an important role in meeting
      the protein demand through the supply of eggs. However, the risk of contamination
      by beta-lactamase-producing Escherichia coli in eggs laid by commercial chickens
      is significant. In this study, we investigated the rate of extended-spectrum beta
      lactamase (ESBL) and plasmid-mediated AmpC (pAmpC) beta-lactamase-producing E.
      coli isolated from layer hens and characterized their molecular background. Among
      the 92 cefotaxime-resistant E. coli isolates, 66 (71.7%) were identified as
      multidrug resistant and 29 showed phenotypic and genotypic characteristics of
      beta-lactamase-producing E. coli. The ESBL/pAmpC genes blaCTX-M-1, blaCTX-M-14,
      blaCTX-M-15, and blaCMY-2 were detected in 1, 6, 5, and 4 isolates, respectively.
      The non-ESBL/pAmpC gene blaTEM-1 was found in 16 isolates. Three isolates
      harbored both blaTEM-1 and blaCTX-M-14 genes. A total of 12 isolates also carried
      class 1 integrons, with 3 different gene cassette arrangements found in 8 of
      these isolates. A pulsed-field gel electrophoresis (PFGE) analysis of the 29 beta
      lactamase-producing E. coli isolates revealed that 4 PFGE patterns were
      consistent with the beta-lactamase gene and layer farm origin, and showed a
      similar antibiotic resistance pattern. Our results suggest that comprehensive
      surveillance and more prudent use of third-generation cephalosporins in
      commercial layer farms is necessary to prevent the dissemination of ESBL/pAmpC
      producing E. coli.

PMID- 30239889
TI  - Patellin1 Negatively Modulates Salt Tolerance by Regulating PM Na+/H+ Antiport
      Activity and Cellular Redox Homeostasis in Arabidopsis.

PMID- 30239890
TI  - Influence of the corn form in the diet and length of fasting before slaughter on
      the performance of overfed mule ducks.
AB  - The aim of this trial was to study the effect of the corn form fed during the
      overfeeding period and of the length of the fasting (LF) before slaughter on the
      performance of overfed mule ducks. A total of 180 ducks were distributed into 9
      groups of 20 birds each, according to a 3 * 3 factorial design that differed
      according to the LF (9, 12, or 15 h) and the ratio of whole corn/corn flour in
      the overfeeding diet (OD): constant ratio of 30/70 [C diet]; progressive change
      from 0/100 to 30/70 [P diet]; or constant ratio of 0/100 [F diet]). At the end of
      the overfeeding period, the birds were slaughtered to measure the weight and
      chemical composition of the fatty liver. No significant interaction between the
      OD and LF was observed. The fatty liver weight was higher (+8%; P = 0.031) in the
      ducks fed the P diet than those fed the F diet. The ones fed the C diet were
      intermediate (709 g). The fatty liver weight was heavier (+7%) in the ducks
      slaughtered after 9 h of fasting than in those slaughtered after 15 h of fasting,
      The weight of fatty liver of birds slaughtered after 12 h was intermediate (711
      g; P < 0.05). The foie gras fat loss during cooking (20% vs. 27%; P = 0.003), DM
      (68.13% vs. 69.3%; P = 0.021), and ash content (0.40% vs. 0.36%; P = 0.010) were
      lower in the group of ducks slaughtered after 9 h of fasting than in the other 2
      groups. In conclusion, the present results suggest that (i) incorporating whole
      corn in the OD at a constant or increasing rate up to 30% significantly improves
      the performance of overfed mule ducks, and (ii) the shorter the fasting time is,
      the greater the weight and the quality of the foie gras will be.

PMID- 30239891
TI  - Simplified, less-invasive left ventricular assist device implantation in patients
      with post-coronary artery bypass grafting.
AB  - Less-invasive left ventricular assist device implantation is becoming the
      technique of choice for implementation of new-generation heart pumps. The less
      invasive technique is particularly useful for patients with a history of cardiac
      surgical procedures, such as coronary artery bypass grafting. Yet, in redo cases,
      severe pericardial adhesions may force experienced operators to opt for
      alternative outflow graft placement, such as in the descending aorta. We propose
      a surgical technique in which the left ventricular device is implanted through a
      limited thoracic incision, with the outflow graft anastomosed to the ascending
      aorta, avoiding collision with coronary bypass grafts. The key element of the
      proposed technique is a tunnel connecting 2 pleural cavities, in which the
      outflow graft is placed, entirely bypassing the pericardium.

PMID- 30239892
TI  - Clinicopathologic Features of Two Patients With Sporadic Amyotrophic Lateral
      Sclerosis Who Maintained Communication Ability for Over 30 Years.
AB  - We report the clinicopathologic features of 2 unrelated patients with sporadic
      amyotrophic lateral sclerosis (SALS) supported by tracheostomy and invasive
      ventilation (TIV) who were able to maintain communication ability for more than
      30 years after disease onset. In both cases, the age at onset was younger than
      the mean, initially the progression of muscle weakness was consistent with that
      in the majority of SALS patients, and TIV became necessary several years after
      disease onset. Thereafter, however, their neurologic deterioration slowed and the
      patients were able to operate computers by facial movements for several decades.
      At autopsy, neuronal loss appeared to be confined to the motor neuron system.
      Furthermore, while Betz cells and lower motor neurons in the spinal anterior
      horns and hypoglossal nucleus were severely depleted, other pyramidal neurons in
      the motor cortex, and lower motor neurons in the other brainstem motor nuclei
      were retained. Neuronal and glial cytoplasmic inclusions immunoreactive for
      phosphorylated 43-kDa TAR DNA-binding protein (TDP-43) were evident in the CNS,
      but in extremely small numbers. The present patients may represent a distinct
      subgroup of patients with SALS who are able to maintain communication ability for
      an extremely long period, accompanied by very mild TDP-43 pathology.

PMID- 30239893
TI  - Comment on: Efficacy and safety of biologics targeting interleukin-6, -12/23 and 
      17 pathways for peripheral psoriatic arthritis: a network meta-analysis.

PMID- 30239894
TI  - Identifying Central Sensitization May Not Tell the Whole Story.

PMID- 30239895
TI  - The potent ITK/BTK inhibitor Ibrutinib is effective for the treatment of
      experimental visceral leishmaniasis caused by Leishmania donovani.
AB  - Background: New drugs are needed for leishmaniasis as current treatments such as
      pentavalent antimonials are toxic and require prolonged administration leading to
      poor patient compliance. Ibrutinib is an anti-cancer drug known to modulate
      Th1/Th2 responses, and has the potential to regulate immunity against infectious
      disease. Methods: In this study, we evaluated the efficacy of oral Ibrutinib as a
      host-targeted treatment for visceral leishmaniasis (VL) caused by L.donovani
      using an experimental mouse model. Results: We found that oral Ibrutinib was
      significantly more effective than the pentavalent antimonial sodium
      stibogluconate (70mg/kg) for the treatment of VL caused by L. donovani. Ibrutinib
      treatment increased the number of IL-4 and IFN-gamma producing NKT cells in the
      liver and spleen, and enhanced granuloma formation in the liver. Further,
      Ibrutinib reduced the influx of Ly6C hi inflammatory monocytes which mediate
      susceptibility to L. donovani. Finally, Ibrutinib treatment was associated with
      the increased production of the cytokines IFN-gamma, TNF-alpha, IL-4 and IL-13 in
      the liver and spleen, which are associated with protection against L. donovani.
      Conclusions: Our findings show that oral Ibrutinib is highly effective for the
      treatment of VL caused by L. donovani and mediates its anti-leishmanial activity
      by promoting host immunity. Therefore, Ibrutinib could be a novel host-targeted
      drug for the treatment of VL.

PMID- 30239897
TI  - Early versus Delayed Extracranial-Intracranial Bypass Surgery in Symptomatic
      Atherosclerotic Occlusion.
AB  - Background: Clinical trials of extracranial-intracranial (EC-IC) bypass surgery
      studied patients in subacute and chronic stage after ischemic event. OBJECTIVE:
      To investigate the short-term outcomes of EC-IC bypass in progressive acute
      ischemic stroke or recent transient ischemic attacks. Methods: The study was a
      retrospective review at a single tertiary referral center from 2008 to 2015.
      Inclusion criteria consisted of EC-IC bypass within 1 yr of last ischemic
      symptoms ipsilateral to atherosclerotic occlusion of internal carotid or middle
      cerebral artery. Early bypass group who underwent surgery within 7 d of last
      ischemic symptoms were compared to late bypass group who underwent surgery >7 d
      from last ischemic symptom. The primary endpoint was perioperative ischemic or
      hemorrhagic stroke or intracranial hemorrhage within 7 d of surgery. Results: Of
      126 patients who underwent EC-IC bypass during the period, 81 patients met
      inclusion criteria, 69 (85%) persons had carotid artery occlusion, 7 (9%) had
      proximal MCA occlusion, and 5 (6%) had both. Early surgery had a 31% (9/29)
      perioperative stroke rate compared to 11.5% (6/52) of patients undergoing late
      bypass (P = .04). Of patients with acute stroke within 7 d of surgery, 41% (7/17)
      had perioperative stroke within 7 d (P = .07). Six of nine patients (67%) with
      blood pressure dependent fluctuation of neurologic symptoms had perioperative
      stroke (P = .049). Conclusion: EC-IC bypass in setting of acute symptomatic
      stroke within 1 wk may confer higher risk of perioperative stroke. Patients
      undergoing expedited or urgent bypass for unstable or fluctuating stroke symptoms
      might be at highest risk for perioperative stroke.

PMID- 30239896
TI  - COPII vesicles can affect the activity of antisense oligonucleotides by
      facilitating the release of oligonucleotides from endocytic pathways.
AB  - RNase H1-dependent, phosphorothioate-modified antisense oligonucleotides (PS
      ASOs) can enter cells through endocytic pathways and need to be released from the
      membrane-enclosed organelles, a limiting step for antisense activity.
      Accumulating evidence has suggested that productive PS-ASO release mainly occurs
      from late endosomes (LEs). However, how PS-ASOs escape from LEs is not well
      understood. Here, we report that upon PS-ASO incubation, COPII vesicles, normally
      involved in ER-Golgi transport, can re-locate to PS-ASO-containing LEs. Reduction
      of COPII coat proteins significantly decreased PS-ASO activity, without affecting
      the levels of PS-ASO uptake and early-to-late endosome transport, but caused
      slower PS-ASO release from LEs. COPII co-localization with PS-ASOs at LEs does
      not require de novo assembly of COPII at ER. Interestingly, reduction of STX5 and
      P115, proteins involved in tethering and fusion of COPII vesicles with Golgi
      membranes, impaired COPII re-localization to LEs and decreased PS-ASO activity.
      STX5 can re-locate to LEs upon PS-ASO incubation, can bind PS-ASOs, and the
      binding appears to be required for this pathway. Our study reveals a novel
      release pathway in which PS-ASO incubation causes LE re-localization of STX5,
      which mediates the recruitment of COPII vesicles to LEs to facilitate endosomal
      PS-ASO release, and identifies another key PS-ASO binding protein.

PMID- 30239899
TI  - Pro-viral miRNAs detected in BALF extracellular vesicles of patients with
      influenza virus-induced ARDS.
AB  - Influenza A virus (IAV) causes severe respiratory infections and alveolar
      epithelial damage resulting in acute respiratory distress syndrome (ARDS).
      Extracellular vesicles (EV) have been shown to mediate cellular crosstalk in
      inflammation by transfer of microRNAs. In this study, we found significant
      changes in the miRNA composition of EVs in the broncho-alveolar lavage fluid
      (BALF) from patients with IAV-induced ARDS. Among the nine significantly
      deregulated microRNAs, miR-17-5p was upregulated in patients' BALF, and in EVs of
      IAV-infected lung epithelial cells (A549). In these cells, transfer of miR-17-5p
      strongly downregulated expression of the antiviral factor Mx1 and significantly
      enhanced IAV replication.

PMID- 30239900
TI  - Healthy Adolescent Performance With Standardized Scoring Tables for the MATRICS
      Consensus Cognitive Battery: A Multisite Study.
AB  - Objective: The aim of this study was to develop standardized scores and scoring
      tables for test performance in healthy adolescents for the Measurement and
      Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus
      Cognitive Battery (MCCB) for each year from 11 to 19 years of age, by sex, with T
      scores and percentile ranks. Methods: A total of 502 healthy participants (aged
      11-19 years) from 7 cohorts from Ireland, Norway, Sweden, and United States, were
      included in this multisite study. Regression-predicted means for the MCCB tests,
      except the social cognition subtest, were calculated using the MCCB test scores
      as outcome variables and age, age2, sex, age * sex as predictors. The regression
      predicted means for each combination of age and sex were added with the residuals
      from the entire cohort to yield the expected distribution of that group. Age
      effects were examined using regression models with age and age2 as predictors.
      Sex differences were examined using Student's t-tests. Results: Significant
      positive age effects were found for all tests, except for the Brief Visuospatial
      Memory Test, revised (BVMT-R; measure of visual learning). Females performed
      significantly better than males on BACS Symbol coding (measure of speed of
      processing) and BVMT-R, while males performed significantly better than females
      on NAB Mazes (measure of reasoning and problem solving). Based on the regression
      predicted distributions of scores, 19 standardized scoring tables for each test
      and domain were created. Conclusions: With the results from this study, we have
      developed an accessible standardized data set of healthy adolescent test
      performance for the MCCB.

PMID- 30239902
TI  - Optimizing Outcome Prediction Scores in Patients Undergoing Endovascular
      Thrombectomy for Large Vessel Occlusions Using Collateral Grade on Computed
      Tomography Angiography.

PMID- 30239901
TI  - Progress and Challenges in Using Oral Cholera Vaccines to Control Outbreaks: The
      Medecins Sans Frontieres Experience.
AB  - The use of oral cholera vaccine (OCV) has increased since 2011, when Shanchol,
      the first OCV suitable for large-scale use, became available. Medecins Sans
      Frontieres considers OCVs an essential cholera outbreak control tool and has
      contributed to generating new evidence on OCV use in outbreaks. We showed that
      large-scale mass campaigns are feasible during outbreaks, documented high short
      term effectiveness and showed that vaccines are likely safe in pregnancy. We
      found that a single-dose regimen has high short-term effectiveness, making rapid
      delivery of vaccine during outbreaks easier, especially given the on-going global
      vaccine shortage. Despite progress, OCV has still not been used widely in some of
      the largest recent outbreaks and thousands of cholera deaths are reported every
      year. While working towards improving our tools to protect those most at-risk of
      cholera, we must strive to use all available effective interventions in efficient
      ways, including OCV, to prevent avoidable deaths today.

PMID- 30239898
TI  - Site-specific amino acid substitution in dodecameric peptides determines the
      stability and unfolding of c-MYC quadruplex promoting apoptosis in cancer cells.
AB  - c-MYC proto-oncogene harbours a transcription-inhibitory quadruplex-forming
      scaffold (Pu27) upstream P1 promoter providing anti-neoplastic therapeutic
      target. Previous reports showed the binding profile of human Cathelicidin peptide
      (LL37) and telomeric G-quadruplex. Here, we truncated the quadruplex-binding
      domain of LL37 to prepare a small library of peptides through site-specific amino
      acid substitution. We investigated the intracellular selectivity of peptides for
      Pu27 over other oncogenic quadruplexes and their role in c-MYC promoter
      repression by dual-luciferase assays. We analysed their thermodynamics of binding
      reactions with c-MYC quadruplex isomers (Pu27, Myc22, Pu19) by Isothermal
      Titration Calorimetry. We discussed how amino acid substitutions and peptide
      helicity enhanced/weakened their affinities for c-MYC quadruplexes and
      characterized specific non-covalent inter-residual interactions determining their
      selectivity. Solution NMR structure indicated that KR12C, the best peptide
      candidate, selectively stabilized the 5'-propeller loop of c-MYC quadruplex by
      arginine-driven electrostatic-interactions at the sugar-phosphate backbone while
      KR12A peptide destabilized the quadruplex inducing a single-stranded hairpin-like
      conformation. Chromatin immunoprecipitations envisaged that KR12C and KR12A
      depleted and enriched Sp1 and NM23-H2 (Nucleoside diphosphate kinase) occupancy
      at Pu27 respectively supporting their regulation in stabilizing and unfolding c
      MYC quadruplex in MCF-7 cells. We deciphered that selective arresting of c-MYC
      transcription by KR12C triggered apoptotic-signalling pathway via VEGF-A-BCL-2
      axis.

PMID- 30239903
TI  - Keel bone differences in laying hens housed in enriched colony cages.
AB  - Keel bone damage may be painful to birds and affect their production. In order to
      better understand the frequency, position, and timepoint of keel bone damage that
      occur during production, the integrity of W-36 laying hen keel bones housed in
      enriched colony cages at 748.4 cm2 (116 in2) was evaluated. At four time points,
      120 birds (10 per cage; three cages per each of four rooms) had keel bones
      evaluated. Each hen was placed in a motion limiting restraint, scanned using
      computed tomography (CT), fitted in vests containing tri-axial accelerometers,
      and placed back in their cages for 21 d. After 21 d, the hens were rescanned and
      returned to their cages. This process was repeated after 133 d. The CT scans were
      imported into Mimics analysis software (Materialise, Plymouth, MI, USA); 3D
      models were made of each keel bone at each time point and exported to 3-matic
      analysis software (Materialise, Plymouth, MI, USA). Each laying hen's keel bone
      model was superimposed onto scans from multiple time points resulting in four
      bone pairings representative of each 21-d period, the 133-d period, and the
      entire duration of the project. Next, the proximal portion of each bone pairing
      was edited to normalize bone shape according to a strict protocol. Additionally,
      each pairing was divided into three portions: distal aspect (3 cm), proximal
      aspect (2 cm), and middle portion (remaining). Whole bone pairing and each bone
      portion was analyzed using the Part Comparison tool in 3-matic. Raw data were
      compiled into three datasets and analyzed in SAS 9.3 using the GLIMMIX procedure
      using a three-level random intercept model. The model controlled for time, part,
      part(time), and system with random intercepts of bird(cage) and cage. Overall,
      results revealed that the greatest morphological changes occurred during the
      first 21-d period with regards to time (P = 0.03) and in the distal aspect of the
      keel with regards to part (P < 0.0001).

PMID- 30239904
TI  - E-Cigarettes May Support Smokers With High Smoking-Related Risk Awareness to Stop
      Smoking in the Short Run: Preliminary Results by Randomized Controlled Trial.

PMID- 30239905
TI  - Acute sleep deprivation and culpable motor vehicle crash involvement.
AB  - Study Objectives: To quantify the relationship between acute sleep deprivation
      and culpable involvement in motor vehicle crashes. Methods: Participants were
      6845 drivers involved in a representative sample of crashes investigated by the
      US Department of Transportation in years 2005-2007. A modified case-control study
      design was used to compare self-reported hours of sleep in the 24 hr before
      crashing between drivers deemed culpable versus nonculpable. Analyses controlled
      for fatigue-related, driver-related, and environmental factors. Specific errors
      that led to crashes were also examined. Results : Drivers who reported having
      slept for 6, 5, 4, and less than 4 hr in the 24 hr before crashing had 1.3 (95%
      confidence interval [CI] = 1.04 to 1.7), 1.9 (1.1 to 3.2), 2.9 (1.4 to 6.2), and
      15.1 (4.2 to 54.4) times the odds, respectively, of having been culpable for
      their crashes, compared with drivers who reported 7-9 hr of sleep. Drivers who
      had slept less than 4 hr had 3.4 (95% CI = 2.1 to 5.6) times the increase in odds
      of culpable involvement in single-vehicle crashes compared with multiple-vehicle
      crashes. Recent change in sleep schedule, typically feeling drowsy upon waking,
      and driving for 3+ hr were also associated with culpability (all p <= 0.013).
      Assuming nonculpable drivers comprised a representative sample of all drivers
      present where crashes occurred, these odds ratios approximate incidence rate
      ratios for culpable crash involvement per unit of time driving. Conclusions:
      Driving after having slept less than 7 hr in a 24 hr period is associated with
      elevated risk of culpable crash involvement. Risk is greatest for drivers who
      have slept less than 4 hr and is manifested disproportionately in single-vehicle
      crashes.

PMID- 30239906
TI  - Functional analysis of ion transport properties and salt tolerance mechanisms of
      RtHKT1 from the recretohalophyte Reaumuria trigyna.
AB  - Reaumuria trigyna is an endangered recretohalophyte and a small archaic feral
      shrub that is endemic to arid and semiarid plateau regions of Inner Mongolia,
      China. Based on transcriptomic data, we isolated a high-affinity potassium
      transporter gene (RtHKT1) from R. trigyna, which encoded a plasma membrane
      localised protein. RtHKT1 was rapidly upregulated by high Na+ or low K+ and
      exhibited different tissue-specific expression patterns before and after stress
      treatment. Transgenic yeast showed tolerance to high Na+ or low K+, while
      transgenic Arabidopsis exhibited tolerance to high Na+ and sensitivity to high
      K+, or high Na+-low K+, confirming that Na+ tolerance in transgenic Arabidopsis
      depends on a sufficient external K+ concentration. Under external high Na+, high
      K+, and low K+ conditions, transgenic yeast accumulated more Na+-K+, Na+, and K+;
      while transgenic Arabidopsis accumulated less Na+-more K+, more Na+, and more Na+
      K+, respectively; indicating that the ion transport properties of RtHKT1 depend
      on the external Na+-K+ environment. Salt stress induced upregulation of some ion
      transporter genes (AtSOS1/AtHAK5/AtKUP5-6), as well as downregulation of some
      genes (AtNHX1/AtAVP1/AtKUP9-12), revealing that multi-ion-transporter synergism
      maintains Na+/K+ homeostasis under salt stress in transgenic Arabidopsis.
      Overexpression of RtHKT1 enhanced K+ accumulation and prevented Na+ transport
      from roots to shoots, improved biomass accumulation and chlorophyll content in
      salt-stressed transgenic Arabidopsis. The proline content and RWC increased
      significantly, and some proline biosynthesis genes (AtP5CS1-2) were also
      upregulated in salt-stressed transgenic plants. These results suggest that RtHKT1
      confers salt tolerance on transgenic Arabidopsis by maintenancing Na+/K+
      homeostasis and osmotic homeostasis.

PMID- 30239907
TI  - Coexistence of Symptoms Associated with Trigeminal Pathways in Chronic and
      Episodic Migraine and the Effects on Quality of Life.
AB  - Objective: The functional impairment in migraine greatly depends on the
      chronicity of the disease. Patients with migraine suffer from sleep difficulties
      and concentration problems. Cranial autonomic symptoms, vertigo, dizziness, and
      cutaneous allodynia are also frequent in patients with migraine. In this paper,
      we aim to investigate the coexistence of these symptoms and their effects on the
      quality of life of patients with chronic and episodic migraine. Methods: The
      study included 1,080 patients with migraine. The presence of cranial autonomic
      symptoms, vertigo/dizziness, cutaneous allodynia, concentration-related
      impairment in function, and abnormal sleep latency was sought in patients with
      questionnaires, and comparisons were made between episodic and chronic migraine
      groups. Results: Abnormal sleep latency and concentration-related impairment in
      function were more frequent in patients with chronic migraine compared with those
      with the episodic form (P < 0.001 for both). Furthermore, these two symptoms were
      significantly more frequent in separate patient groups with cranial autonomic
      symptoms, vertigo/dizziness, and cutaneous allodynia than patients without (P <
      0.005). Conclusion: Abnormal sleep latency and concentration-related impairment
      in function were more frequent in patients with chronic migraine than those with
      the episodic form. Cranial autonomic symptoms, vertigo/dizziness, and cutaneous
      allodynia were significantly coexisting in migraine patients.

PMID- 30239909
TI  - Extracellular Vesicles for Research on Psychiatric Disorders.
AB  - Extracellular vesicles (EVs) have gained increasing attention as underexplored
      intercellular communication mechanisms in basic science and as potential
      diagnostic tools in translational studies, particularly those related to cancers
      and neurological disorders. This article summarizes accumulated findings in the
      basic biology of EVs, EV research methodology, and the roles of EVs in brain cell
      function and dysfunction, as well as emerging EV studies in human brain
      disorders. Further research on EVs in neurobiology and psychiatry may open the
      door to a better understanding of intercellular communications in healthy and
      diseased brains, and the discovery of novel biomarkers and new therapeutic
      strategies in psychiatric disorders.

PMID- 30239908
TI  - A single molecule analysis of H-NS uncouples DNA binding affinity from DNA
      specificity.
AB  - Heat-stable nucleoid structuring protein (H-NS) plays a crucial role in gene
      silencing within prokaryotic cells and is important in pathogenesis. It was
      reported that H-NS silences nearly 5% of the genome, yet the molecular mechanism
      of silencing is not well understood. Here, we employed a highly-sensitive single
      molecule counting approach, and measured the dissociation constant (KD) of H-NS
      binding to single DNA binding sites. Charged residues in the linker domain of H
      NS provided the most significant contribution to DNA binding affinity. Although H
      NS was reported to prefer A/T-rich DNA (a feature of pathogenicity islands) over
      G/C-rich DNA, the dissociation constants obtained from such sites were nearly
      identical. Using a hairpin unzipping assay, we were able to uncouple non-specific
      DNA binding steps from nucleation site binding and subsequent polymerization. We
      propose a model in which H-NS initially engages with non-specific DNA via
      reasonably high affinity (~60 nM KD) electrostatic interactions with basic
      residues in the linker domain. This initial contact enables H-NS to search along
      the DNA for specific nucleation sites that drive subsequent polymerization and
      gene silencing.

PMID- 30239910
TI  - A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm
      antibody-associated vasculitis.
AB  - Objectives: Glucocorticoids (GCs) are a mainstay of treatment for patients with
      ANCA-associated vasculitis (AAV) but are associated with significant adverse
      effects. Effective remission induction in severe AAV using extremely limited GC
      exposure has not been attempted. We tested an early rapid GC withdrawal induction
      regimen for patients with severe AAV. Methods: Patients with active MPO- or PR3
      ANCA vasculitis or ANCA-negative pauci-immune glomerulonephritis were included.
      Induction treatment consisted of two doses of rituximab, 3 months of low-dose CYC
      and a short course of oral GC (for between 1 and 2 weeks). Clinical, biochemical
      and immunological outcomes as well as adverse events were recorded. Results: A
      total of 49 patients were included, with at least 12 months of follow-up in 46.
      All patients achieved remission, with decreases observed in creatinine,
      proteinuria, CRP, ANCA level and BVAS. Three patients requiring dialysis at
      presentation became dialysis independent. Two patients required the introduction
      of maintenance GC for treatment of vasculitis. Overall outcomes were comparable
      to those of two matched cohorts (n = 172) from previous European Vasculitis
      Society (EUVAS) trials, but with lower total exposure to CYC and GCs (P < 0.001)
      and reduced rates of severe infections (P = 0.02) compared with the RITUXVAS
      (rituximab versus cyclophosphamide in AAV) trial. We found no new cases of
      diabetes in the first year compared with historic rates of 8.2% from the EUVAS
      trials (P = 0.04). Conclusion: Early GC withdrawal in severe AAV is as effective
      for remission induction as the standard of care and is associated with reduced GC
      related adverse events.

PMID- 30239911
TI  - Diets, obesity and inflammation for cognitive disorder: which is a true risk?
      Which is a confounding risk?

PMID- 30239912
TI  - The British Society for Rheumatology biologic DMARD safety guidelines in
      inflammatory arthritis.

PMID- 30239913
TI  - Whole transcriptome analysis of the pectoralis major muscle reveals molecular
      mechanisms involved with white striping in broiler chickens.
AB  - White striping (WS) is one of the most common myopathies identified in broiler
      chickens leading to substantial production losses, where the incidence reaches
      12% in commercial chickens. It occurs primarily in heavier chickens being a
      modification of the breast muscle characterized by the presence of pale parallel
      streaks in the same orientation of the muscle fibers. Since the WS etiology
      remains unclear, we aimed to identify the biological and genetic mechanisms
      involved in its occurrence through the whole transcriptome analysis of WS in
      affected and unaffected chicken breast muscles. A total of 11,177 genes were
      expressed in the pectoralis major muscle. Out of those, 1,441 genes were
      differentially expressed (FDR <= 0.01) between the two analyzed groups, being,
      respectively, 772 genes upregulated and 669 downregulated in the WS affected
      group. A total of 36 significantly overrepresented GO terms related to WS
      myopathy were enriched, and the most relevant biological processes were
      activation of immune system, angiogenesis, hypoxia, cell death, and striated
      muscle contraction. The unbalance of those biological processes may trigger the
      occurrence of the WS phenotype in broilers. The possible lack of capillary blood
      supply homogeneously in the muscle triggers the hypoxia, following the activation
      of glycolysis, calcium signaling and apoptosis related genes facilitating the
      tissue damage and WS incidence.

PMID- 30239914
TI  - The association between driving time and unhealthy lifestyles: a cross-sectional,
      general population study of 386 493 UK Biobank participants.
AB  - Background: Driving is a common type of sedentary behaviour; an independent risk
      factor for poor health. The study explores whether driving is also associated
      with other unhealthy lifestyle factors. Methods: In a cross-sectional study of UK
      Biobank participants, driving time was treated as an ordinal variable and other
      lifestyle factors dichotomized into low/high risk based on guidelines. The
      associations were explored using chi-square tests for trend and binary logistic
      regression. Results: Of the 386 493 participants who drove, 153 717 (39.8%) drove
      <1 h/day; 140 140 (36.3%) 1 h/day; 60 973 (15.8%) 2 h/day; and 31 663 (8.2%) >=3
      h/day. Following adjustment for potential confounders, driving >=3 h/day was
      associated with being overweight/obese (OR = 1.74, 95% CI: 1.64-1.85), smoking
      (OR = 1.48, 95% CI: 1.37-1.63), insufficient sleep (1.70, 95% CI: 1.61-1.80), low
      fruit/vegetable intake (OR = 1.26, 95% CI: 1.18-1.35) and low physical activity
      (OR = 1.05, 95% CI: 1.00-1.11), with dose relationships for the first three, but
      was not associated with higher alcohol consumption (OR = 0.94, 95% CI: 0.87
      1.02). Conclusions: Sedentary behaviour, such as driving, is known to have an
      independent association with adverse health outcomes. It may have additional
      impact mediated through its effect on other aspects of lifestyle. People with
      long driving times are at higher risk and might benefit from targeted
      interventions.

PMID- 30239915
TI  - CC chemokine ligand 19 might act as the main bursal T cell chemoattractant factor
      during IBDV infection.
AB  - Infectious bursa disease virus (IBDV) pathogenesis is characterized by increased
      numbers of T cells and decreased numbers of B cells in the bursa. Currently,
      little is about the key factor that affects T migration into bursa. In humans, CC
      chemokine ligand 19 (CCL19) recruits monocytes and neutrophils and is usually
      involved in various inflammatory disorders. The aim of this study was to assess
      the roles of CCL19 in driving peripheral blood cells infiltration into bursa of
      Fabricius of chickens infected with IBDV. Bursal samples were collected from
      chickens of the infection group and the control group on day 1, 3, 5, and 7 post
      infection (dpi) with IBDV. The mRNA or protein levels of ccl19 and ccr7 genes in
      bursae were determined by real-time PCR and immunohistochemistry (IHC) methods.
      Moreover, an in vitro chemotaxis assay was performed to evaluate the chemotaxis
      ability of CCL19 and bursal total protein. The results have displayed that the
      mRNA levels of ccl19 were significantly increased on 1, 3, 5, and 7 dpi in the
      infection group. The highest value amounted to 73.4-fold of the control group.
      Also, the mRNA levels of CCR7, the receptor of CCL19, began to increase on 3 dpi
      and reached to the highest value of 206.3-fold on 5 dpi after IBDV infection.
      Then the gene expression of CCR7 in bursae of the infection group returned to the
      normal level. IHC results of CCL19 protein level accorded with the mRNA levels of
      CCL19, with the highest value on 5 dpi. Then, in vitro chemotaxis test
      demonstrated that the total bursal protein had the ability of recruiting
      peripheral white blood cells (PWBC) and the migration percentage was a little
      higher than that of the blank control with only basal medium (P < 0.05). Taken
      together, these data suggest that CCL19 acts as a chicken PWBC chemotactic factor
      and facilitate the infiltration of PWBC (especially T cells) into the bursae
      after IBDV infection.

PMID- 30239916
TI  - Response to Letter: One-hour post-load hyperglycemia: implications for prediction
      and prevention of type 2 diabetes.

PMID- 30239917
TI  - Intra-annual dynamics of phloem formation and ultrastructural changes in sieve
      tubes in Fagus sylvatica.
AB  - Despite increased interest in the timing and dynamics of phloem formation,
      seasonal changes in the structure of phloem sieve elements remain largely
      unexplored. To understand better the dynamics of phloem formation and the
      functioning of sieve tubes in the youngest phloem in Fagus sylvatica L., we
      investigated repeatedly taken phloem samples during the growing season of 2017 by
      means of light microscopy, and transmission and scanning electron microscopy.
      Phloem formation started with the expansion of the overwintered early phloem
      sieve tubes adjacent to the cambium and concurrent cambial cell production. The
      highest phloem growth rate was observed in general 1 week after the onset of
      cambial cell production, whereas the transition from early to late phloem
      occurred at the end of May. Cambial cell production ceased at the end of July.
      The final width of the phloem increment was 184 +/- 10 MUm, with an early phloem
      proportion of 59%. Collapse of older phloem tissue is a progressive process,
      which continuously occurred during the sampling period. Collapse of early phloem
      sieve tubes started shortly after the cessation of cambial cell production. Prior
      to the onset of radial growth, late phloem from the previous year represented 80%
      of the total non-collapsed part; during the growth period, this percentage
      decreased to 20%. Differences were observed in both sieve tube ultrastructure and
      sieve plate geometry between the youngest and older phloem. However, sieve plates
      were never completely occluded by callose, suggesting that processes affecting
      the functionality of sieve tubes may differ in the case of regular collapse or
      injury. The youngest parts of the phloem increment from the previous year (i.e.,
      previous late phloem) continue functioning for some time in the current growing
      season, but the two-step development of overwintered phloem cells also ensures a
      sufficient translocation pathway for photosynthates to the actively growing
      tissues.

PMID- 30239919
TI  - Characteristics of cephalosporin-resistant Salmonella isolates from poultry in
      Korea, 2010-2017.
AB  - Cephalosporins are the key drugs for the treatment of salmonellosis. Resistance
      to cephalosporins in Salmonella spp. has become a serious public health concern
      worldwide. Although the sales of cephalosporins have increased by five times from
      2008 to 2016 in Korea, limited information is available on cephalosporin
      resistance in Korea. Therefore, we aimed to investigate the trends in prevalence
      and characteristics of cephalosporin-resistant Salmonella isolates from poultry
      in Korea in the period between 2010 and 2017. A total of 141 Salmonella isolates
      were collected from various poultry industry sources, and 38 (27.0%) among them
      showed resistance to cephalosporins. In particular, resistance to the following
      cephalosporins increased significantly over the seven-year period cephalothin
      (from 5.0% to 29.2%), cephalexin, cefuroxime, cefotaxime, and ceftazidime (from
      0% to 25.0%), and cefepime (from 0% to 12.5%). In addition, 12 isolates carried a
      beta-lactamase gene. A non-extended-spectrum beta-lactamase (ESBL) and plasmid
      mediated AmpC beta-lactamase (pAmpC) gene, blaTEM-1, was found in three isolates
      in the periods of 2010 to 2011 and 2012 to 2013, respectively. The blaCTX-M-79 (n
      = 4) and blaCTX-M-15 (n = 1) for ESBL genes and blaCMY-2 (n = 1) for pAmpC genes
      were only present in the 2016-2017 period. All ESBL/pAmpC-positive isolates had
      high minimum inhibitory concentrations for most cephalosporins and showed multi
      drug resistance. In a conjugation experiment, the transfer of blaCTX-M-79 and
      blaCMY-2 genes was confirmed in transconjugants, which showed similar pattern of
      antibiotic resistance. This demonstrates that ESBL/pAmpC-producing Salmonella
      isolates might be transmitted to humans through contaminated poultry products.
      These findings suggest the need for the development of monitoring program and the
      guidelines for prudent use of antimicrobial agents in the poultry industry in
      Korea.

PMID- 30239921
TI  - Registry report of the prevalence of ECG abnormalities and their relation to
      patient characteristics in an asymptomatic population.
AB  - Background: Cardiovascular disease is the leading cause of morbidity and
      mortality in developed countries. Many patients do not experience symptoms before
      a first major cardiovascular event. Resting electrocardiogram (ECG) may help
      identify asymptomatic individuals with a high risk of cardiovascular disease.
      Objective: We sought to determine the prevalence of ECG abnormalities in an
      apparently symptom-free adult population within a prospective registry. Methods:
      The registry consisted of 4739 consecutive apparently healthy individuals [age
      62.8 +/- 6.2 (SD) years; 54% female], referred by their General Practitioners
      between 2009 and 2013. Patient demographics, and clinical data were obtained,
      alongside blood tests and a resting ECG. Results: ECG abnormalities were present
      in 1509 (31.8%) subjects and were commoner with increasing age (F = 0.161, p =
      0.01), systolic (F = 0.134, p = 0.01) and diastolic (F = 0.44, p = 0.01) blood
      pressure and waist circumference (F = 0.53, p = 0.01). Left ventricular
      hypertrophy (LVH) was the most common abnormality (n = 281) and was positively
      associated with systolic (F = 0.12, p = 0.01) and diastolic blood pressure (F =
      0.99, p = 0.01) and male gender (X2 = 60.5, p < 0.01). All ECG abnormalities
      (except for LVH) were associated with an increasing age, while right bundle
      branch block (F = 0.041, p = 0.01) and atrial fibrillation (n = 29; F = 0.036, p
      = 0.05) were associated with the presence of diabetes mellitus (n = 211). Only
      left bundle branch block (n = 50) was associated with angina (F = 0.05, p =
      0.01). Conclusions: Unrecognized cardiac abnormalities are common in middle-aged
      men and women with no overt symptoms. ECG offers the potential to identify these
      abnormalities and provide earlier intervention and treatment, and possibly
      improve cardiovascular outcome.

PMID- 30239923
TI  - Revisiting an old idea: engineering against vector-borne diseases in the domestic
      environment.

PMID- 30239922
TI  - Towards Evidence-Based Guidelines in Neurological Surgery.
AB  - Neurological surgery practice is based on the science of balancing probabilities.
      A variety of clinical guidance documents have influenced how we collectively
      practice our art since the early 20th century. The quality of the science within
      these guidelines varies widely, as does their utility in positively shaping our
      practice.The guidelines development process in neurological surgery has evolved
      significantly over the last 30 yr. Historically based in expert opinion, as a
      specialty we have increasingly relied on objective medical evidence to guide our
      clinical practice. We assessed the changing practice guidelines development
      process and the impact of scientifically robust guidelines on patient care.The
      evolution of the guidelines development process in neurological surgery was
      chronicled. Several subspecialty guidelines were extracted and reviewed in
      detail. Their impact on practice patterns was evaluated. The importance of
      evidence-based research and practice guidelines development was
      discussed.Evidence-based practice guidelines serve to chronicle multiple
      acceptable treatment options and help us move towards more standardized care for
      specific disease processes. They help refute false "standards of care."
      Guidelines-based care supported by solid medical evidence has the potential to
      streamline patient care and improve patient outcomes. The guidelines development
      process identifies areas, issues, and strategies for which little medical
      evidence exists, as well as topics that need focused scientific investigation and
      future study.The production of evidence-based practice recommendations is a vital
      part of furthering our specialty. Guidelines development advances our science,
      augments the resident education process, and protects our practice from undue
      external influence.

PMID- 30239918
TI  - A Revised Diagnostic Classification of Canine Glioma: Towards Validation of the
      Canine Glioma Patient as a Naturally Occurring Preclinical Model for Human
      Glioma.
AB  - The National Cancer Institute-led multidisciplinary Comparative Brain Tumor
      Consortium (CBTC) convened a glioma pathology board, comprising both veterinarian
      and physician neuropathologists, and conducted a comprehensive review of 193
      cases of canine glioma. The immediate goal was to improve existing glioma
      classification methods through creation of a histologic atlas of features, thus
      yielding greater harmonization of phenotypic characterization. The long-term goal
      was to support future incorporation of clinical outcomes and genomic data into
      proposed simplified diagnostic schema, so as to further bridge the worlds of
      veterinary and physician neuropathology and strengthen validity of the dog as a
      naturally occurring, translationally relevant animal model of human glioma. All
      cases were morphologically reclassified according to a new schema devised by the
      entire board, yielding a majority opinion diagnosis of astrocytoma (43, 22.3%),
      19 of which were low-grade and 24 high-grade, and oligodendroglioma (134, 69.4%),
      35 of which were low-grade and 99 were high-grade. Sixteen cases (8.3%) could not
      be classified as oligodendroglioma or astrocytoma based on morphology alone and
      were designated as undefined gliomas. The simplified classification scheme
      proposed herein provides a tractable means for future addition of molecular data,
      and also serves to highlight histologic similarities and differences between
      human and canine glioma.

PMID- 30239920
TI  - An endocannabinoid receptor polymorphism modulates affective processing under
      stress.
AB  - Stress has a critical impact on affective and cognitive processing. Based on
      rodent data suggesting that endocannabinoid signaling via CB1 receptors serves as
      an emotional buffer, we hypothesized that a common variant of the gene coding for
      the CB1 receptor modulates affective processing under stress (CNR1; rs1049353 A
      vs G allele). Therefore, 139 participants, genotyped for this polymorphism,
      underwent a stress or control manipulation before they viewed emotionally neutral
      and negative pictures in a magnetic resonance imaging scanner. The ventromedial
      prefrontal cortex, known for its crucial role in emotion regulation, was
      significantly more activated in AA/AG vs GG genotype carriers when viewing
      negative pictures after stress. Under no-stress conditions, AA/AG genotype
      carriers showed enhanced crosstalk between the ventrolateral prefrontal cortex
      and the amygdala. We further assessed participants' 24 h-delayed memory for the
      presented pictures and found that memory performance correlated with amygdala and
      hippocampus activity and connectivity in stressed carriers of the AA/AG but not
      the GG genotype. These findings underline the modulatory role of the
      endocannabinoid system in stress effects on emotion and cognition and provide
      insights into the neural mechanisms that may contribute to the suggested
      protective effect of the AA/AG genotype of the CB1 receptor polymorphism against
      stress-related psychopathologies.

PMID- 30239924
TI  - Comment on: Efficacy and safety of biologics targeting interleukin-6, -12/23 and 
      17 pathways for peripheral psoriatic arthritis: a network meta-analysis: reply.

PMID- 30239925
TI  - Comment on: The multisystemic nature and natural history of joint hypermobility
      syndrome and Ehlers-Danlos syndrome in children.

PMID- 30239927
TI  - Commentary: Flow State (Trading the Sweat Spot for the Sweet Spot): A Roadmap to
      Measure and Enhance Workplace Growth and Well-Being.

PMID- 30239928
TI  - UniLectin3D, a database of carbohydrate binding proteins with curated information
      on 3D structures and interacting ligands.
AB  - Lectins, and related receptors such as adhesins and toxins, are glycan-binding
      proteins from all origins that decipher the glycocode, i.e. the structural
      information encoded in the conformation of complex carbohydrates present on the
      surface of all cells. Lectins are still poorly classified and annotated, but
      since their functions are based on ligand recognition, their 3D-structures
      provide a solid foundation for characterization. UniLectin3D is a curated
      database that classifies lectins on origin and fold, with cross-links to
      literature, other databases in glycosciences and functional data such as known
      specificity. The database provides detailed information on lectins, their bound
      glycan ligands, and features their interactions using the Protein-Ligand
      Interaction Profiler (PLIP) server. Special care was devoted to the description
      of the bound glycan ligands with the use of simple graphical representation and
      numerical format for cross-linking to other databases in glycoscience. We
      conceived the design of the database architecture and the navigation tools to
      account for all organisms, as well as to search for oligosaccharide epitopes
      complexed within specified binding sites. UniLectin3D is accessible at
      https://www.unilectin.eu/unilectin3D.

PMID- 30239929
TI  - Delusional infestation managed in a combined tropical medicine and psychiatry
      clinic.
AB  - Background: Delusional infestation (DI) is a well-recognised delusional disorder
      presenting as the persisting belief in the presence of parasitic or other
      infestations. Combined clinics have been run by dermatology and psychiatry in a
      small number of centres. Here we report the first few years of a unique combined
      clinic run with experts in infectious diseases/tropical medicine and psychiatric
      management of DI. Methods: We reviewed all patients seen at the combined
      assessment clinics run at the Liverpool School of Tropical Medicine between 19
      December 2011 and 31 October 2016. Data were collected prospectively as part of
      clinical assessment. Descriptive analysis of these data was performed to examine
      clinical features at assessment, investigations performed and treatment outcomes.
      Results: A total of 75 patients were assessed and 52 (69%) were given the formal
      diagnosis of DI. A history of travel was given by 64% of individuals but no
      significant tropical or infectious diagnosis was made. Of those who returned for
      follow-up, 61% reported improvement in symptoms. The Clinical Global Impressions
      Severity scale improvement was 1.36 for DI patients but only 0.63 for non-DI
      patients. DI patients were more impaired at baseline (5.0 vs 4.1). Health anxiety
      was the most common diagnosis seen in those not considered to have DI.
      Conclusions: Combined clinics to treat DI are effective in improving patient
      outcome. A significant minority of patients referred do not have a diagnosis of
      DI.

PMID- 30239930
TI  - Multiple Treatment Comparison in Narcolepsy: a Network Meta-analysis.
AB  - Study Objectives: Randomised clinical trials (RCTs) that compared the safety and
      efficacy of medical treatments for narcolepsy were analysed using network meta
      analysis. Methods: The RCTs in narcolepsy were searched. Network meta-analysis
      compared efficacy and safety of multiple treatments, multi-arm studies, and multi
      criteria treatment decisions, based on a random model that assumed heterogeneity
      between studies, with corrections for multi-arm studies. Results: Fourteen RCTs,
      three drug treatments, and six doses were identified: sodium oxybate (6 and 9
      g/d), modafinil (between 200 and 400 mg/d), and pitolisant (up to 20 and up to 40
      mg/d). Significant heterogeneity (>50%) between studies was found in 12/14
      studies for almost all endpoints, but between-design consistency was present. For
      ESS and MWT, sodium oxybate 9 g/d, modafinil, and pitolisant up to 40 mg/d had
      similar efficacy. Pitolisant 40 mg/d and sodium oxybate 9 g/d in two nightly
      doses had similar efficacy in reducing cataplexy. A good safety profile
      characterised by a TEAE incidence risk ratio (IRR) <1.5 was found for all the
      compared treatments, except for sodium oxybate 9 g/d. Although no significant
      difference was found, Pitolisant 40mg was shown with the best P-scores for the
      benefit/Risk ratio. Conclusions: Modafinil (200-400 mg/d), sodium oxybate 9 g/d,
      and pitolisant up to 40 mg/d had similar efficacy in reducing excessive day time
      sleepiness. Only sodium oxybate 9 g/d and pitolisant up to 40 mg/d were shown
      with a comparable beneficial effect on cataplexy. Overall, Pitolisant was found
      with the best P-score on the benefit/risk ratio.

PMID- 30239926
TI  - Highly efficient genome editing via CRISPR-Cas9 in human pluripotent stem cells
      is achieved by transient BCL-XL overexpression.
AB  - Genome editing of human induced pluripotent stem cells (iPSCs) is instrumental
      for functional genomics, disease modeling, and regenerative medicine. However,
      low editing efficiency has hampered the applications of CRISPR-Cas9 technology in
      creating knockin (KI) or knockout (KO) iPSC lines, which is largely due to
      massive cell death after electroporation with editing plasmids. Here, we report
      that the transient delivery of BCL-XL increases iPSC survival by ~10-fold after
      plasmid transfection, leading to a 20- to 100-fold increase in homology-directed
      repair (HDR) KI efficiency and a 5-fold increase in non-homologous end joining
      (NHEJ) KO efficiency. Treatment with a BCL inhibitor ABT-263 further improves HDR
      efficiency by 70% and KO efficiency by 40%. The increased genome editing
      efficiency is attributed to higher expressions of Cas9 and sgRNA in surviving
      cells after electroporation. HDR or NHEJ efficiency reaches 95% with dual editing
      followed by selection of cells with HDR insertion of a selective gene. Moreover,
      KO efficiency of 100% can be achieved in a bulk population of cells with
      biallelic HDR KO followed by double selection, abrogating the necessity for
      single cell cloning. Taken together, these simple yet highly efficient editing
      strategies provide useful tools for applications ranging from manipulating human
      iPSC genomes to creating gene-modified animal models.

PMID- 30239931
TI  - Asymetric red-blue hypertrophic hand and tenosynovitis due to acrodermatitis
      chronica atrophicans.

PMID- 30239934
TI  - 18F-FDG-PET/CT scanning-clinical usefulness beyond cancer.

PMID- 30239933
TI  - I could have consulted fishermen.

PMID- 30239935
TI  - Histamine: Neural circuits and new medications.
AB  - Histamine was first identified in the brain about 50 years ago, but only in the
      last few years have researchers gained an understanding of how it regulates
      sleep/wake behavior. We provide a translational overview of the histamine system,
      from basic research to new clinical trials demonstrating the usefulness of drugs
      that enhance histamine signaling. The tuberomammillary nucleus is the sole
      neuronal source of histamine in the brain, and like many of the arousal systems,
      histamine neurons diffusely innervate the cortex, thalamus, and other wake
      promoting brain regions. Histamine has generally excitatory effects on target
      neurons, but paradoxically, histamine neurons may also release the inhibitory
      neurotransmitter GABA. New research demonstrates that activity in histamine
      neurons is essential for normal wakefulness, especially at specific circadian
      phases, and reducing activity in these neurons can produce sedation. The number
      of histamine neurons is increased in narcolepsy, but whether this affects brain
      levels of histamine is controversial. Of clinical importance, new compounds are
      becoming available that enhance histamine signaling, and clinical trials show
      that these medications reduce sleepiness and cataplexy in narcolepsy.

PMID- 30239936
TI  - Systematic assessment of the toxicity and potential mechanism of graphene
      derivatives in vitro and in vivo.
AB  - Graphene is a two-dimensional crystal that is stripped from pristine graphite and
      made of single layer of carbon atoms. Containing numerous functional groups,
      graphene derivatives (GDs) could be easily modified and have aroused great
      attention for potential applications in biomedicine. However, pristine graphene
      and graphene oxide (GO) could arouse cell and animal toxicity. To screen GDs with
      high biocompatibility applied for biomedicine, general comparison was performed
      about the toxicities of six GDs with diverse types of surface modification, size
      and redox state, including GO, reduced GO (rGO), graphene quantum dot (GQD),
      aminated GQD (GQD-NH2), carboxyl GQD (GQD-COOH), graphene oxide quantum dot
      (GOQD). By contrast, it was found that large particle size, oxidation state, high
      concentration, long exposure time were unfavorable factors affecting the cell
      viability. We further explored the mechanism of different toxicity, which could
      be contribute to cell membrane destruction by sharpened edges of GDs (LDH
      release, hemolysis), ROS production, immuno-inflammatory responses and activation
      of apoptotic pathways (IKK/IkappaBalpha/NF-kappaB and BAX/BCL-2). Overall, our
      combined data primarily explored the related biochemical and molecular mechanism
      underlying the biological behaviors and toxicity of GDs, and we also identified
      GQD, GQD-NH2, GQD-COOH, and GOQD could be safely used for biomedical application
      as drug carriers.

PMID- 30239932
TI  - I260Q DNA polymerase beta highlights precatalytic conformational rearrangements
      critical for fidelity.
AB  - DNA polymerase beta (pol beta) fills single nucleotide gaps in DNA during base
      excision repair and non-homologous end-joining. Pol beta must select the correct
      nucleotide from among a pool of four nucleotides with similar structures and
      properties in order to maintain genomic stability during DNA repair. Here, we use
      a combination of X-ray crystallography, fluorescence resonance energy transfer
      and nuclear magnetic resonance to show that pol beta's ability to access the
      appropriate conformations both before and upon binding to nucleotide substrates
      is integral to its fidelity. Importantly, we also demonstrate that the inability
      of the I260Q mutator variant of pol beta to properly navigate this conformational
      landscape results in error-prone DNA synthesis. Our work reveals that
      precatalytic conformational rearrangements themselves are an important underlying
      mechanism of substrate selection by DNA pol beta.

PMID- 30239937
TI  - Responding to Cholera in Haiti: Implications for the National Plan to Eliminate
      Cholera by 2022.

PMID- 30239940
TI  - Revisiting the past and building for the future: a series of commentaries
      discussing important papers from the journal's archive and placing them in an
      updated context.

PMID- 30239938
TI  - A phosphate-targeted dinuclear Cu(II) complex combining major groove binding and
      oxidative DNA cleavage.
AB  - Free radical generation is an inevitable consequence of aerobic existence and is
      implicated in a wide variety of pathological conditions including cancer,
      cardiovascular disease, ageing and neurodegenerative disorder. Free radicals can,
      however, be used to our advantage since their production is catalysed by
      synthetic inorganic molecules-termed artificial metallonucleases-that cut DNA
      strands by oxidative cleavage reactions. Here, we report the rational design and
      DNA binding interactions of a novel di-Cu2+ artificial metallonuclease [Cu2(tetra
      (2-pyridyl)-NMe-naphthalene)Cl4] (Cu2TPNap). Cu2TPNap is a high-affinity binder
      of duplex DNA with an apparent binding constant (Kapp) of 107 M(bp)-1. The agent
      binds non-intercalatively in the major groove causing condensation and G-C
      specific destabilization. Artificial metallonuclease activity occurs in the
      absence of exogenous reductant, is dependent on superoxide and hydrogen peroxide,
      and gives rise to single strand DNA breaks. Pre-associative molecular docking
      studies with the 8-mer d(GGGGCCCC)2, a model for poly[d(G-C)2], identified
      selective major groove incorporation of the complex with ancillary Cu2+-phosphate
      backbone binding. Molecular mechanics methods then showed the d(GGGGCCCC)2 adduct
      to relax about the complex and this interaction is supported by UV melting
      experiments where poly[d(G-C)2] is selectively destabilized.

PMID- 30239939
TI  - Effect of soil water availability on intra-annual xylem and phloem formation and
      non-structural carbohydrate pools in stem of Quercus pubescens.
AB  - Non-structural carbohydrates (NSCs, i.e., starch and soluble sugars) are
      frequently quantified in the context of tree response to stressful events (e.g.,
      drought), because they serve as a carbon reservoir for growth and respiration, as
      well as providing a critical osmotic function to maintain turgor and vascular
      transport under different environmental conditions. We investigated the impact of
      soil water availability on intra-annual leaf phenology, radial growth dynamics
      and variation in NSC amounts in the stem of pubescent oak (Quercus pubescens
      Willd.). from a sub-Mediterranean region. For this purpose, trees growing at two
      nearby plots differing in bedrock and, consequently, soil characteristics (F
      eutric cambisol on eocene flysch bedrock and L-rendzic leptosol on paleogenic
      limestone bedrock) were sampled. Non-structural carbohydrates were analysed in
      outer xylem and living phloem (separately for non-collapsed and collapsed parts).
      Results showed that xylem and phloem increments were 41.6% and 21.2%,
      respectively, wider in trees from F plot due to a higher rate of cell production.
      In contrast, the amount of NSCs and of soluble sugars significantly differed
      among the tissue parts and sampling dates but not between the two plots. Starch
      amounts were the highest in xylem, which could be explained by the abundance of
      xylem parenchyma cells. Two clear seasonal peaks of the starch amount were
      detected in all tissues, the first in September-November, in the period of leaf
      colouring and falling, and the second in March-April, i.e., at the onset of
      cambial cell production followed by bud development. The amounts of free sugars
      were highest in inner phloem + cambium, at the sites of active growth. Soil water
      availability substantially influenced secondary growth in the stem of Q.
      pubescens, whereas NSC amounts seemed to be less affected. The results show how
      the intricate relationships between soil properties, such as water availability,
      and tree performance should be considered when studying the impact of stressful
      events on the growth and functioning of trees.

PMID- 30239941
TI  - Podoconiosis pathogenesis: renewed use of an historical archive.

PMID- 30239942
TI  - The foundations for a global elimination programme for onchocerciasis.

PMID- 30239943
TI  - Lessons from history: viral surveillance in 1940s East Africa: Epidemiological
      notes on some viruses isolated in Uganda, G. W. A. Dick, Transactions of the
      Royal Society of Tropical Medicine and Hygiene, 1953;47(1):13-48.

PMID- 30239944
TI  - The rise of leishmaniasis in the twenty-first century.

PMID- 30239945
TI  - Filarial lymphoedema on the road to elimination.

PMID- 30239946
TI  - The influence of Arnoldo Gabaldon on the present malaria elimination strategy.

PMID- 30239947
TI  - New engineered phenolic biosensors based on the AraC regulatory protein.
AB  - Customized transcription factors that control gene expression in response to
      small molecules can act as endogenous molecular biosensors and are valuable tools
      for synthetic biology. We previously engineered the Escherichia coli regulatory
      protein AraC to respond to non-native inducers such as D-arabinose and triacetic
      acid lactone. Those prior studies involved the construction and screening of
      individual 4- or 5-site saturation mutagenesis libraries, followed by iterative
      rounds of positive- and negative fluorescence-activated cell sorting (FACS). Here
      we describe an improved screening platform and the isolation of several new and
      potentially useful AraC variants that respond to vanillin and salicylic acid. To
      increase throughput and reduce total screening time, selection steps were added
      to the sorting workflow. Two different site-saturation libraries and a random
      mutagenesis library were pooled together and >108 variants were subjected to
      iterative FACS and selection in search of variants responding to a panel of
      compounds. The new phenolic-sensing variants show responses >100-fold over
      background and are highly specific towards their target compound. The isolation
      of these variants further demonstrates the potential for engineering the AraC
      transcriptional regulatory protein for molecular sensing and reporting, and our
      improved screening system should prove effective in designing similar biosensors.

PMID- 30239948
TI  - Item development and performance of tobacco product and regulation perception
      items for the Health Information National Trends Survey.
AB  - Introduction: Emerging tobacco products have become increasingly popular, and the
      FDA extended its authority to all products meeting the definition of a tobacco
      product in 2016. These changes may lead to shifts in public perceptions about
      tobacco products and regulation, and national surveys are attempting to assess
      these perceptions at the population level. This manuscript describes the item
      development and cognitive interviewing of the tobacco product and regulation
      perception items included in two tobacco-focused cycles of the Health Information
      National Trends Survey (HINTS-FDA). Methods: Cognitive interviewing was used to
      investigate how respondents comprehended and responded to tobacco product and
      regulation perception items. Adult participants (n=20) were selected purposively
      to oversample current tobacco users, and were interviewed in two iterative
      rounds. Weighted descriptive statistics from the fielded HINTS-FDA surveys
      (n=5,474) were also calculated. Results: Items were generally interpreted as
      intended, and participants meaningfully discriminated between tobacco products
      when assessing addiction perceptions. Response selection issues involved
      inconsistent reporting among participants with little knowledge or ambivalent
      opinions about either government regulation or tobacco products and ingredients,
      which resolved when a "don't know" response option was included in the survey.
      The fielded survey found that a non-negligible proportion of the population do
      not have clear perceptions of emerging tobacco products or government regulation.
      Conclusions: A "don't know" response option is helpful for items assessing many
      emerging tobacco products, but presents several analytic challenges that should
      be carefully considered. Multiple items assessing specific tobacco product and
      regulation perception items are warranted in future surveys.

PMID- 30239949
TI  - Thermal challenge alters the transcriptional profile of the breast muscle in
      turkey poults.
AB  - Extremes in temperature represent environmental stressors that impact the well
      being and economic value of poultry. As homeotherms, young poultry with immature
      thermoregulatory systems are especially susceptible to thermal extremes. Genetic
      variation and differences in gene expression resulting from selection for
      production traits, likely contribute to thermal stress response. This study was
      designed to investigate in vivo transcriptional changes in the breast muscle of
      young turkey poults from an unselected randombred line and one selected for 16 wk
      body weight under hot and cold thermal challenge. Newly hatched turkey poults
      were brooded for 3 d at one of 3 temperatures: control (35 degrees C), cold (31
      degrees C), or hot (39 degrees C). Samples of the pectoralis major were harvested
      and subjected to deep RNA sequencing. Significant differential gene expression
      was observed in both growth-selected and randombred birds at both temperature
      extremes when compared to control-brooded poults. Growth-selected birds responded
      to thermal stress through changes in genes predicted to have downstream
      transcriptional effects and that would result in reduced muscle growth. Slower
      growing randombred birds responded to thermal stress through modulation of lipid
      related genes, suggesting reduction in lipid storage, transport, and synthesis,
      consistent with changes in energy metabolism required to maintain body
      temperature.

PMID- 30239950
TI  - High dietary inorganic selenium has minimal effects on turkeys and selenium
      status biomarkers.
AB  - The current NRC turkey Se requirement is 0.2 MUg Se/g diet. Recent studies
      evaluating tissue Se, glutathione peroxidase (GPX) activities, and selenoprotein
      transcript expression concluded that the dietary Se requirement of the turkey
      poult should be raised to 0.4 MUg Se/g when supplemented with inorganic Se. The
      FDA currently limits Se inclusion in premixed diets for poultry and other
      livestock species to 0.3 MUg Se/g diet. Thus, there is a need to investigate the
      effect of high dietary Se (>1.0 MUg Se/g) in turkeys. The present study fed
      turkey poults 2 and 5 MUg Se/g diet to characterize tissue Se accumulation in
      turkey poults fed high dietary inorganic Se and to evaluate the efficacy of
      selenoprotein activity and transcript expression as biomarkers of high Se status.
      Day-old male poults were fed 0.4, 2, or 5 MUg Se/g for 28 d. There was no
      significant effect of Se supplementation on poult growth. Supplementation with 5
      MUg Se/g diet resulted in Se concentrations that were 5.6X, 1.7X, 1.9X, and 2.0X
      greater than Se-adequate levels in liver, kidney, breast, and thigh,
      respectively, and GPX activities in plasma, red cells, liver, kidney, and heart
      that were <=2.0X Se-adequate values. In liver, kidney, heart, gizzard, breast, or
      thigh, no selenoprotein transcript was increased >=2.0X, and no selenoprotein
      transcript was decreased <=0.5X by 2 or 5 MUg Se/g diet as compared to poults fed
      0.4 MUg Se/g diet. Of the 112 Se status biomarkers reported in this study, liver
      Se concentration was the only biomarker markedly altered by high Se status. This
      study provides evidence of no adverse effects in turkey poults fed up to 5 MUg
      Se/g diet as inorganic Se. Thus, the FDA limit for Se supplementation in turkey
      feed can be safely raised to 0.5 MUg Se/g diet. Future studies are needed to
      identify biomarkers for high Se status and to better understand how turkeys
      maintain Se homeostasis and resist Se toxicity.

PMID- 30239951
TI  - Heat stress tolerance determines the survival and growth of introduced Canadian
      sugar maple in subtropical China.
AB  - The introduction of species contributes to both ecological restoration and
      regional economics, while serving as a potential strategy to conserve species
      under rapid climate change. Despite an anticipated significant increase in
      temperature at high latitudes by the end of the 21st century, very few
      experimental migration trials have been conducted regarding large climate range
      changes. We employed a provenance trial by introducing a temperate sugar maple
      (Acer saccharum Marsh) of three provenances with a mean annual temperature of 3.0
      degrees C in Manitoba, 4.2  degrees C in Quebec and 9.4  degrees C in Ontario,
      Canada, to 15.8  degrees C at an introduced site in subtropical China. We
      measured survival, growth, summer photosynthesis in the field and stress
      resistance responses under a temperature gradient in growth chambers with first
      year seedlings. We found that the Ontario provenance had the highest propensity
      for survival and growth, followed by the Quebec provenance, while the Manitoba
      provenance had the lowest. The photosynthetic parameters of the seedlings changed
      over time of the day, with the Ontario provenance having a higher photosynthesis
      rate and stomatal conductance than the Quebec and Manitoba provenances.
      Furthermore, the growth chamber results revealed that the Ontario provenance had
      the best physiological adjustment for self-protection from heat stress, followed
      by the Quebec and Manitoba provenances. Our results suggested that the change in
      climate range drove the survival and growth of introduced seedlings and that the
      tolerance to summer heat stress through physiological mechanisms was responsible
      for the success of species introduction, from a cold to a warm climate.

PMID- 30239952
TI  - mTORC1 inhibition in pediatric low-grade glioma depletes glutathione and
      therapeutically synergizes with carboplatin.
AB  - Background: Pediatric low-grade glioma (pLGG) often initially respond to front
      line therapies such as carboplatin, but more than 50% of treated tumors
      eventually progress and require additional therapy. The discovery that pLGG often
      contain mammalian Target of Rapamycin (mTOR) activation, new treatment modalities
      and combinations are now possible for patients. The purpose of this study was to
      determine if carboplatin is synergistic with the mTORC1 inhibitor everolimus in
      pLGG. Methods: We treated four pLGG cell lines and one patient-derived xenograft
      line representing various pLGG genotypes, including NF1 loss, BRAF-KIAA1549
      fusion, and BRAF V600E mutation, with carboplatin and/or everolimus and performed
      assays for growth, cell proliferation, and cell death. Immunohistochemistry as
      well as in vivo and in vitro metabolomics studies were also performed. Results:
      Carboplatin synergized with everolimus in all of our four pLGG cell lines
      (combination index< 1 at Fa 0.5). Combination therapy was superior at inhibiting
      tumor growth in vivo. Combination treatment increased levels of apoptosis as well
      as gamma-H2AX phosphorylation compared to either agent alone. Everolimus
      treatment suppressed the conversion of glutamine and glutamate into glutathione
      both in vitro and in vivo. Exogenous glutathione reversed the effects of
      carboplatin and everolimus. Conclusions: The combination of carboplatin and
      everolimus was effective at inducing cell death and slowing tumor growth in pLGG
      models. Everolimus decreased the amount of available glutathione inside the cell,
      preventing the detoxification of carboplatin and inducing increased DNA damage
      and apoptosis.

PMID- 30239953
TI  - Intersection of e-cigarette use and gender on transitions in cigarette smoking
      status: Findings across waves 1 and 2 of the Population Assessment of Tobacco and
      Health (PATH) study.
AB  - Introduction: Cigarette smokers report using e-cigarettes to reduce or quit
      smoking but findings are mixed regarding the benefit and risk of e-cigarettes in
      this population, and effects of gender are unknown. Methods: The Population
      Assessment of Tobacco and Health (PATH; waves 1 & 2; adult interviews) was used
      to evaluate relationships among wave 1 e-cigarette use (daily, non-daily, never)
      and gender and their association with transitions (quit vs. current; relapse vs.
      former) in cigarette smoking status across waves 1 and 2 of the PATH study.
      Results: Daily e-cigarette users had higher odds of quitting smoking (OR=1.56,
      95% CI=1.12, 2.18) compared to never e-cigarette users. Conversely, daily and non
      daily e-cigarette users were at greater risk of smoking relapse (OR=1.84, 95%
      CI=1.15, 2.94 and OR=1.85, 95% CI=0.99, 3.46 respectively) compared to never e
      cigarette users. Women were less likely to quit smoking compared to men
      independent of e-cigarette use (OR=0.76, 95% CI=0.59, 0.99). In stratified
      analyses, daily or non-daily e-cigarette use did not increase the likelihood of
      quitting or relapse in women. In men, daily and non-daily e-cigarette users were
      at greater risk of smoking relapse (OR=2.96, 95% CI=1.49, 5.86 and OR=3.05, 95%
      CI=1.29, 7.17, respectively) compared to men who were never e-cigarette users.
      Conclusions: Findings identify e-cigarettes as a potential aid for smoking
      cessation, but also as a potential risk for smoking relapse in men only. Overall,
      women were less likely to quit smoking, and e-cigarette use did not impact their
      ability to quit or to stay quit. Implications: Cigarette smokers report using e
      cigarettes to reduce or quit smoking but findings are mixed regarding the benefit
      and risk of e-cigarettes in this population. Using data from the newly available
      Population Assessment of Tobacco and Health (PATH; waves 1 & 2; adult
      interviews), our findings identify e-cigarettes as a potential aid for smoking
      cessation, but also identify e-cigarettes as a potential risk for smoking relapse
      in men only. These findings may have implications for the regulation of e
      cigarettes by the FDA and the benefit-cost ratio of e-cigarette use in smokers.

PMID- 30239954
TI  - Congenital absence of the pericardium and tricuspid regurgitation.

PMID- 30239955
TI  - Models of arthropathy: what can we learn from them to improve patient care?

PMID- 30239957
TI  - A simulation-based approach to statistical alignment.
AB  - Classic alignment algorithms utilize scoring functions which maximize similarity
      or minimize edit distances. These scoring functions account for both insertion
      deletion (indel) and substitution events. In contrast, alignments based on
      stochastic models aim to explicitly describe the evolutionary dynamics of
      sequences by inferring relevant probabilistic parameters from input sequences.
      Despite advances in stochastic modeling during the last two decades, scoring
      based methods are still dominant, partially due to slow running times of
      probabilistic approaches. Alignment inference using stochastic models involves
      estimating the probability of events, such as the insertion or deletion of a
      specific number of characters. In this work, we present SimBa-SAl, a simulation
      based approach to statistical alignment inference, which relies on an explicit
      continuous Markov process for both indels and substitutions. SimBa-SAl has
      several advantages. First, using simulations, it decouples the estimation of
      event probabilities from the inference stage, which allows the introduction of
      accelerations to the alignment inference procedure. Second, it is general and can
      accommodate various stochastic models of indel formation. Finally, it allows
      computing the maximum-likelihood alignment, the probability of a given pair of
      sequences integrated over all possible alignments, and sampling alternative
      alignments according to their probability. We first show that SimBa-SAl allows
      accurate estimation of parameters of the long-indel model previously developed by
      Miklos, Lunter and Holmes in 2004. We next show that SimBa-SAl is more accurate
      than previously developed pairwise alignment algorithms, when analyzing simulated
      as well as empirical datasets. Finally, we study the goodness-of-fit of the long
      indel and TKF91 models. We show that while the long-indel model fits the datasets
      better than TKF91, there is still room for improvement concerning the realistic
      modeling of evolutionary sequence dynamics.

PMID- 30239958
TI  - REM Sleep without Atonia with REM Sleep-Related Motor Events: Broadening the
      Spectrum of REM Sleep Behavior Disorder.
AB  - Objective: To assess the presence of increased REM-related motor activity during
      sleep, by questionnaires for REM sleep behavior disorder (RBD), in subjects with
      "isolated" REM sleep without atonia (RWA). Subjects and Methods: Two-hundred-and
      forty-nine patients were consecutively enrolled, with age >=18 years, sharing
      bedroom with a roommate, and without a severe health, neurologic or cognitive
      problem. Motor activity during sleep was assessed by means of the RBD Screening
      Questionnaire (RBDSQ) and the RBD questionnaire-Hong Kong (RBDQ-HK). A video
      polysomnographic recording was obtained and the REM Atonia Index was computed.
      Thirteen subjects were diagnosed to have RBD while the remaining 236 were
      subdivided into two subgroups: 34 subjects with "low" (<0.8) and 202 subjects
      with "high" Atonia Index (>=0.8). Results: RBDSQ and RBDQ-HK were both higher in
      subjects with low Atonia index than in those with high Atonia Index, as well as
      number of drugs taken and number of comorbidities. No effect of antidepressant
      use was found on Atonia index and a multiple regression analysis showed that
      Atonia Index was significantly (inversely) correlated only with the behavioral
      score obtained with the RBDQ-HK. Conclusion: Our study shows that individuals
      with isolated RWA have an increased motor activity/behavioral pattern during
      sleep, although this activity does not allow to diagnose RBD. Our findings
      broaden the spectrum of RBD and the condition that we have identified should be
      better characterized in order to understand its eventual development into fully
      blown RBD or not.

PMID- 30239956
TI  - A unique intra-molecular fidelity-modulating mechanism identified in a viral RNA
      dependent RNA polymerase.
AB  - Typically not assisted by proofreading, the RNA-dependent RNA polymerases (RdRPs)
      encoded by the RNA viruses may need to independently control its fidelity to
      fulfill virus viability and fitness. However, the precise mechanism by which the
      RdRP maintains its optimal fidelity level remains largely elusive. By solving 2.1
      2.5 A resolution crystal structures of the classical swine fever virus (CSFV)
      NS5B, an RdRP with a unique naturally fused N-terminal domain (NTD), we
      identified high-resolution intra-molecular interactions between the NTD and the
      RdRP palm domain. In order to dissect possible regulatory functions of NTD, we
      designed mutations at residues Y471 and E472 to perturb key interactions at the
      NTD-RdRP interface. When crystallized, some of these NS5B interface mutants
      maintained the interface, while the others adopted an 'open' conformation that no
      longer retained the intra-molecular interactions. Data from multiple in vitro
      RdRP assays indicated that the perturbation of the NTD-RdRP interactions clearly
      reduced the fidelity level of the RNA synthesis, while the processivity of the
      NS5B elongation complex was not affected. Collectively, our work demonstrates an
      explicit and unique mode of polymerase fidelity modulation and provides a vivid
      example of co-evolution in multi-domain enzymes.

PMID- 30239959
TI  - Multicenter Study of Pipeline Flex for Intracranial Aneurysms.
AB  - Background: The Pipeline Flex (PED Flex; Medtronic, Dublin, Ireland) was designed
      to facilitate deployment and navigation compared to its previous iteration to
      reduce the rate of technical events and complications. OBJECTIVE: To assess the
      neurological morbidity and mortality rates of the PED Flex at 30 d. Methods:
      Information from 9 neurovascular centers was retrospectively obtained between
      July 2014 and March 2016. Data included patient/aneurysm characteristics,
      periprocedural events, clinical, and angiographic outcomes. Multivariate logistic
      regression was performed to determine predictors of unfavorable clinical outcome
      (modified Rankin Scale [mRS] > 2). Results: A total of 205 patients harboring 223
      aneurysms were analyzed. The 30-d neurological morbidity and mortality rates were
      1.9% (4/205) and 0.5% (1/205), respectively. The rate of intraprocedural events
      without neurological morbidity was 6.8% (14/205), consisting of intraprocedural
      ischemic events in 9 patients (4.5%) and hemorrhage in 5 (2.4%). Other technical
      events included difficulty capturing the delivery wire in 1 case (0.5%) and
      device migration after deployment in another case (0.5%). Favorable clinical
      outcome (mRS 0-2) was achieved in 186 patients (94.4%) at discharge and in 140
      patients (94.5%) at 30 d. We did not find predictors of clinical outcomes on
      multivariate analysis. Conclusion: The 30-d rates of neurological morbidity and
      mortality in this multicenter cohort using the PED Flex for the treatment of
      intracranial aneurysms were low, 1.9% (4/205) and 0.5% (1/205), respectively. In
      addition, technical events related to device deployment were also low, most
      likely due to the latest modifications in the delivery system.

PMID- 30239962
TI  - Characterization of intestinal immune response to Clostridium perfringens
      infection in broiler chickens.
AB  - Necrotic enteritis toxin B (NetB)-producing Clostridium perfringens (CP) type A
      is the etiological agent of necrotic enteritis (NE) - an economically significant
      disease in broiler chickens. Understanding the immune response to CP infection in
      broiler chickens is becoming important to develop effective vaccines against NE.
      An experiment was conducted to determine the expression levels of selected
      cytokine genes in the intestine and cecal tonsil of CP-challenged broiler
      chickens. In a floor-pen housing, broiler chickens were randomly assigned to the
      following treatment groups: 1) bacitracin methylene disalicylate (BMD)-free
      control diet with no CP challenge (CX), 2) BMD-supplemented diet with no CP
      challenge (CM), 3) BMD-free control diet with CP challenge (PCX), or 4) BMD
      supplemented diet with CP challenge (PCM). The establishment of CP infection was
      confirmed, with the treatment groups exposed to CP having a 1.5 to 2-fold higher
      CP levels (P < 0.05) compared to the non-exposed groups. On day 1 and 7 post
      challenge, jejunal segments and cecal tonsils were collected from experimental
      chickens for quantitative real-time RT-PCR analysis to determine the expression
      levels of interleukin (IL)-1beta, interferon-gamma (IFN-gamma), IL-2, IL-13, IL
      17, IL-10, and transforming growth factor (TGF)-beta genes. Levels of antibodies
      to CP recombinant proteins were also determined in the plasma of experimental
      chickens. Results indicated that on day 7 post-challenge, IL-1beta
      (proinflammatory cytokine), IL-13 (Th2 cytokine), and IL-17 (Th17 cytokine) were
      upregulated (P < 0.05) in CP-challenged PCX and PCM treatments, compared to the
      unchallenged (control) CX and CM treatments. A reverse trend was observed for TGF
      beta (anti-inflammatory cytokine), while no change was observed in IFN-gamma (Th1
      cytokine). Levels of plasma antibodies (IgY) to CP recombinant proteins were
      higher in CP-challenged treatments (PCX and PCM; P < 0.05), compared to their
      corresponding controls (CX and CM). It was concluded that CP infection induced
      inflammatory response in the intestine of broiler chickens, and the mechanisms of
      inflammation are probably mediated via Th2 and Th17 cells.

PMID- 30239963
TI  - Impacts Of Inference Method And Dataset Filtering On Phylogenomic Resolution In A
      Rapid Radiation of Ground Squirrels (Xerinae: Marmotini).
AB  - Phylogenomic datasets are illuminating many areas of the Tree of Life. However,
      the large size of these datasets alone may be insufficient to resolve problematic
      nodes in the most rapid evolutionary radiations, because inferences in zones of
      extraordinarily low phylogenetic signal can be sensitive to the model and method
      of inference, as well as the information content of loci employed. We used a
      dataset of > 3,950 ultraconserved element (UCE) loci from a classic mammalian
      radiation, ground-dwelling squirrels of the tribe Marmotini (Sciuridae: Xerinae),
      to assess sensitivity of phylogenetic estimates to varying per-locus information
      content across 4 different inference methods (RAxML, ASTRAL, NJst, SVDquartets).
      Persistent discordance was found in topology and bootstrap support between
      concatenation- and coalescent-based inferences; among methods within the
      coalescent framework; and within all methods in response to different filtering
      scenarios. Contrary to some recent empirical UCE-based studies, filtering by
      information content did not promote complete among-method concordance.
      Nevertheless, filtering did improve concordance relative to randomly selected
      locus sets, largely via improved consistency of two-step summary methods
      (particularly NJst) under conditions of higher average per-locus variation (and
      thus increasing gene tree precision). The benefits of dataset filtering are
      notably variable among classes of inference methods and across different
      evolutionary scenarios, reiterating the complexities of resolving rapid
      radiations, even with robust taxon and character sampling.

PMID- 30239960
TI  - Isolation of avian nephritis virus from chickens showing enteric disorders.
AB  - Runting-stunting syndrome (RSS) is one of the diseases associated with many
      detected viruses. In Brazil, there were reports of several enteric disease
      outbreaks in chickens in which avian nephritis virus (ANV) was detected; however,
      the role of ANV in the outbreaks and whether the virus was a causative agent of
      these cases of enteric diseases were not determined. The aim of this study was to
      isolate ANV in specific pathogen-free (SPF) chicken embryonated eggs (CEE) from
      the enteric contents of chickens showing signs of RSS. For this purpose, 22
      samples of chicken enteric contents that were positive only for ANV were
      inoculated into 7 and 14-day-old SPF-CEE via the yolk sac route and incubated for
      5 d, with a total of 3 passages. Virus isolation was confirmed by the presence of
      embryo injuries, detection of viral RNA by RT-PCR, and visualization of viral
      particles using electron microscopy. Therefore, the 7-day-old inoculated embryos
      showed dwarfism, gelatinous consistency, hemorrhage, and edema in the embryos,
      whereas the 14-day-old did not show any alteration. Viral RNA was detected in the
      embryos of both ages of inoculation, and the same viral particles were
      visualized. The embryos from the mock group showed no alteration and were
      negative for all the tests. The viral cDNA was sequenced, and the molecular and
      phylogenetic analyses showed that the Brazilian isolates are more related with
      the ANV-1 serotype group; the sequences of these isolates showed a high
      percentage of nucleotide (86.4 to 94.9%) and amino acid (92.3 to 98.7%)
      similarity with other sequences from China, Japan, Australia, and the United
      States that belong to this serotype previously classified group. In this study,
      we isolated 8 samples of ANV in SPF-CEE from enteric content samples from
      chickens with RSS. In doing so, we showed the pathological injuries to the embryo
      caused by the virus and the molecular characterization of a part of the ORF 1b
      gene of the virus.

PMID- 30239964
TI  - Sporotrichoid Fish Tank Granuloma.

PMID- 30239966
TI  - Rhon DI, Snodgrass SJ, Cleland JA, Greenlee TA, Sissel CD, Cook CE. Comparison of
      downstream health care utilization, costs, and long-term opioid use for physical
      therapist management versus opioid therapy management after arthroscopic hip
      surgery. Phys Ther. 2018;98:348-356.

PMID- 30239965
TI  - Site-directed mutagenesis: role of lid region for T1 lipase specificity.
AB  - A broad substrate specificity enzyme that can act on a wide range of substrates
      would be an asset in industrial application. T1 lipase known to have broad
      substrate specificity in its native form apparently exhibits the same active
      sites as polyhydroxylalkanoate (PHA) depolymerase. PhaZ6Pl is one of the PHA
      depolymerases that can degrade semicrystalline P(3HB). The objective of this
      study is to enable T1 lipase to degrade semicrystalline P(3HB) similar to PhaZ6Pl
      while maintaining its native function. A structural study on PhaZ6Pl contains no
      lid in its structure and therefore T1 lipase was designed with removal of its lid
      region. BSLA lipase was chosen as the reference protein for T1 lipase
      modification since it contains no lid. Initially, structures of both enzymes were
      compared via protein-protein superimposition in 3D-space and the location of the
      lid region of T1 lipase was highlighted. A total of three variants of T1 lipase
      without lid were successfully designed by referring to BSLA lipase (a lipase
      without lid). The ability of T1 lipase without lid variants in degrading P(3HB)
      was investigated quantitatively. All the variants showed activity towards the
      substrate which confirmed that T1 lipase without lid is indeed able to degrade
      P(3HB). In addition, D2 was recorded to have the highest activity amongst other
      variants. Results obtained in this study highlighted the fact that native T1
      lipase is a versatile hydrolase enzyme which does not only record triglyceride
      degradation but also P(3HB) by simply removing the lid region.

PMID- 30239967
TI  - O'Sullivan PB, Caneiro JP, O'Keeffe M, et al. Cognitive functional therapy: an
      integrated behavioral approach for the targeted management of disabling low back
      pain. Phys Ther. 2018;98:408-423.

PMID- 30239968
TI  - Wisdom and Courage.
AB  - Laurita M. (Laurie) Hack, DPT, PhD, MBA, FAPTA: , has contributed to the physical
      therapy profession as an educator, researcher, and academic leader (Fig. 1 ).

PMID- 30239969
TI  - "Branches From the Same Tree".

PMID- 30239970
TI  - News From the Foundation for Physical Therapy.

PMID- 30239971
TI  - Phylogeny, macroevolutionary trends and historical biogeography of sloths:
      insights from a Bayesian morphological clock analysis.
AB  - Sloths, like other xenarthrans, are an extremely interesting group of mammals
      that, after a long history of evolution and diversification in South America,
      became established on islands in the Caribbean and later reached North America
      during the Great American Biotic Interchange. In all three regions, they were
      part of the impressive Pleistocene megafauna. Most taxa became extinct and only
      two small, distantly related tree-dwelling genera survived. Here we incorporate
      several recently described genera of sloths into an assembled morphological data
      supermatrix and apply Bayesian inference, using phylogenetic and morphological
      clock methods, to 64 sloth genera. Thus, we investigate the evolution of the
      group in terms of the timing of divergence of different lineages and their
      diversity, morphological disparity and biogeographical history. The phylogeny
      obtained supports the existence of the commonly recognized clades for the group.
      Our results provide divergence time estimates for the major clades within
      Folivora that could not be dated with molecular methods. Lineage diversity shows
      an early increase, reaching a peak in the Early Miocene followed by a major drop
      at the end of the Santacrucian (Early Miocene). A second peak in the Late Miocene
      was also followed by a major drop at the end of the Huayquerian (Late Miocene).
      Both events show differential impact at the family level. After that, a slight
      Plio-Pleistocene decline was observed before the marked drop with the extinction
      at the end of the Pleistocene. Phenotypic evolutionary rates were high during the
      early history of the clade, mainly associated with Mylodontidae, but rapidly
      decreased to lower values around 25 Ma, whereas Megalonychidae had lower rates at
      the beginning followed by a steady increase, peaking during the Late Miocene and
      the Pliocene. Morphological disparity showed a similar trend, with an early
      increase, followed by a slowly increasing phase through the Late Oligocene and
      Early Miocene, and ending with another increase beginning at the middle of the
      Miocene. Biogeographic analysis showed southern South America as the most
      probable area of origin of the clade and the main region in which the early
      diversification events took place. Both Megatheriinae and Nothrotheriinae basal
      nodes were strongly correlated with Andean uplift events, whereas the early
      history of Mylodontidae is closely associated with southern South America and
      also shows an early occupation of the northern regions. Within Megalonychidae,
      our results show Choloepus as a descendant of an island dispersing ancestor and a
      probable re-ingression to South America by a clade that originated in Central or
      North America.

PMID- 30239972
TI  - Impaired Right Temporoparietal Junction-Hippocampus Connectivity in Schizophrenia
      and Its Relevance for Generating Representations of Other Minds.
AB  - Schizophrenia is associated with impaired and exaggerated Theory of Mind
      processes, pointing on alterations in generating a representation of another
      person's mind. Despite recent work on healthy subjects suggesting that a coupling
      between the right temporoparietal junction (rTPJ) and the hippocampus is relevant
      for building representations of others' intentions, the neural basis of related
      dysfunctions in patients with schizophrenia remains unclear. Therefore, we used
      structural and functional magnetic resonance imaging together with a modified
      prisoner's dilemma game to test the hypotheses, that patients show dysfunctional
      social updating on behavioral level accompanied by altered rTPJ-hippocampus
      coupling on a functional and a structural level. During the task, 31 patients
      with schizophrenia and 20 healthy controls interacted with 3 playing partners,
      who behaved according to stable strategies competitively, cooperatively, or
      randomly. Our data show that patients adapted their social behavior less flexibly
      to the playing partners than healthy controls, indicating differences in forming
      mental representations of the counterparts' intentions. Patients showed lower
      functional connectivity between the rTPJ and temporal lobe regions such as the
      hippocampus, the fusiform gyrus, and the middle temporal gyrus, indicating that
      in patients the rTPJ fails to integrate memory-informed processing streams during
      mental state inferences. Remarkably, the rTPJ-hippocampus coupling accounted for
      the participants' adaptive social behavior in the task, suggesting that a neural
      pathway relevant for updating social knowledge and forming forward predictions in
      social interactions is altered in schizophrenia.

PMID- 30239973
TI  - Successful treatment with anakinra of an HIV-associated immune reconstitution
      inflammatory syndrome mimicking adult-onset Still's disease.

PMID- 30239974
TI  - Perfluorobutanesulfonic acid disrupts pancreatic organogenesis and regulation of
      lipid metabolism in the zebrafish, Danio rerio.
AB  - Since phase-out of highly persistent perfluorosulfonates in the U.S. from non
      stick and stain-resistant products in the early 2000s, perfluorobutanesulfonic
      acid (PFBS) has replaced these compounds as a primary surfactant. Measurements of
      PFBS in environmental and human samples have been rising in recent years, raising
      concerns about potential negative health effects. We previously found that
      embryonic exposures to a related compound, perfluorooctanesulfonic acid (PFOS),
      decreased pancreas length and insulin-producing islet area in zebrafish embryos
      (Danio rerio). The objective of this study was to compare the effects of PFBS
      exposures on pancreatic organogenesis with our previous PFOS findings.
      Dechorionated zebrafish embryos from two different transgenic fish lines
      (Tg(insulin:GFP), Tg(ptf1a:GFP)) were exposed to 0 (0.01% DMSO), 16, or 32 uM
      PFBS daily beginning at 1 day post fertilization (dpf) until 4 and 7 dpf when
      they were examined using fluorescent microscopy for islet area and morphology,
      and exocrine pancreas length. PFBS-exposed embryos had significantly increased
      caudal fin deformities, delayed swim bladder inflation, and impaired yolk
      utilization. Incidence of fish with significantly stunted growth and truncated
      exocrine pancreas length was significantly increased, although these two effects
      occurred independently. Islet morphology revealed an increased incidence of
      severely hypomorphic islets (areas lower than the 1st percentile of controls) and
      an elevated occurrence of fragmented islets. RNA Seq data (4 dpf) also identify
      disruptions in regulation of lipid homeostasis. Overall, this work demonstrates
      that PFBS exposure can perturb embryonic development, energy homeostasis, and
      pancreatic organogenesis.

PMID- 30239975
TI  - R2s for Correlated Data: Phylogenetic Models, LMMs, and GLMMs.
AB  - Many researchers want to report an R2 to measure the variance explained by a
      model. When the model includes correlation among data, such as phylogenetic
      models and mixed models, defining an R2 faces two conceptual problems. (i) It is
      unclear how to measure the variance explained by predictor (independent)
      variables when the model contains covariances. (ii) Researchers may want the R2
      to include the variance explained by the covariances by asking questions such as
      "How much of the data is explained by phylogeny?" Here, I investigate three R2s
      for phylogenetic and mixed models. Rresid2 is an extension of the ordinary least
      squares R2 that weights residuals by variances and covariances estimated by the
      model; it is closely related to Rglmm2 presented by Nakagawa and Schielzeth
      (2013). R2pred is based on predicting each residual from the fitted model and
      computing the variance between observed and predicted values. Rlik2 is based on
      the likelihood of fitted models and therefore reflects the amount of information
      that the models contain. These three R2s are formulated as partial R2s, making it
      possible to compare the contributions of predictor variables and variance
      components (phylogenetic signal and random effects) to the fit of models. Because
      partial R2s compare a full model with a reduced model without components of the
      full model, they are distinct from marginal R2s that partition additive
      components of the variance. The properties of the R2s for phylogenetic models
      were assessed using simulations for continuous and binary response data
      (phylogenetic generalized least squares and phylogenetic logistic regression).
      Because the R2s are designed broadly for any model for correlated data, the R2s
      were also compared for LMMs and GLMMs. Rresid2, Rpred2, and Rlik2 all have
      similar performance in describing the variance explained by different components
      of models. However, Rpred2 gives the most direct answer to the question of how
      much variance in the data is explained by a model. Rresid2 is most appropriate
      for comparing models fit to different datasets, because it does not depend on
      sample sizes. And Rlik2 is most appropriate to assess the importance of different
      components within the same model applied to the same data, because it is most
      closely associated with statistical significance tests.

PMID- 30239977
TI  - AtALMT3 is involved in malate efflux induced by phosphorus deficiency in
      Arabidopsis thaliana root hairs.
AB  - Under phosphorus (P)-deficient conditions, organic acid secretion from roots
      plays an important role in P mobilization from insoluble P in the soil. This
      study, we characterized AtALMT3, a homolog of the Arabidopsis thaliana aluminum
      activated malate transporter family gene. Among the 14 AtALMT family genes, only
      AtALMT3 was significantly up-regulated in P-deficient roots. AtALMT3
      promoter::beta-glucuronidase is expressed in the epidermis in roots, especially
      in root hair cells. AtALMT3 protein was localized in the plasma membrane and in
      small vesicles. Fluorescence of AtALMT3::GFP was not observed on the vacuole
      membrane of protoplast after lysis, indicating that AtALMT3 localizes mainly in
      the plasma membrane. Compared to wild-type (WT) line, malate exudation in the
      AtALMT3-knockdown line (atalmt3-1) and overexpression line (atalmt3-2) under P
      deficiency were, respectively, 37% and 126%. By contrast, no significant
      difference was found in citrate exudation among these lines. The complementation
      of atalmt3-1 line with the AtALMT3 recovered the malate exudation to the level of
      WT. Taken together, these results suggest that AtALMT3 is localized root hair the
      membranes that it is involved in malate efflux in response to P-deficiency.

PMID- 30239976
TI  - Role of aIF1 in Pyrococcus abyssi translation initiation.
AB  - In archaeal translation initiation, a preinitiation complex (PIC) made up of
      aIF1, aIF1A, the ternary complex (TC, e/aIF2-GTP-Met-tRNAiMet) and mRNA bound to
      the small ribosomal subunit is responsible for start codon selection. Many
      archaeal mRNAs contain a Shine-Dalgarno (SD) sequence allowing the PIC to be
      prepositioned in the vicinity of the start codon. Nevertheless, cryo-EM studies
      have suggested local scanning to definitely establish base pairing of the start
      codon with the tRNA anticodon. Here, using fluorescence anisotropy, we show that
      aIF1 and mRNA have synergistic binding to the Pyrococcus abyssi 30S. Stability of
      30S:mRNA:aIF1 strongly depends on the SD sequence. Further, toeprinting
      experiments show that aIF1-containing PICs display a dynamic conformation with
      the tRNA not firmly accommodated in the P site. AIF1-induced destabilization of
      the PIC is favorable for proofreading erroneous initiation complexes. After aIF1
      departure, the stability of the PIC increases reflecting initiator tRNA fully
      base-paired to the start codon. Altogether, our data support the idea that some
      of the main events governing start codon selection in eukaryotes and archaea
      occur within a common structural and functional core. However, idiosyncratic
      features in loop 1 sequence involved in 30S:mRNA binding suggest adjustments of
      e/aIF1 functioning in the two domains.

PMID- 30239978
TI  - Mitochondrial Genome Fragmentation Unites the Parasitic Lice of Eutherian
      Mammals.
AB  - Organelle genome fragmentation has been found in a wide range of eukaryotic
      lineages; however, its use in phylogenetic reconstruction has not been
      demonstrated. We explored the use of mitochondrial (mt) genome fragmentation in
      resolving the controversial suborder-level phylogeny of parasitic lice (order
      Phthiraptera). There are ~5,000 species of parasitic lice in four suborders
      (Amblycera, Ischnocera, Rhynchophthirina and Anoplura), which infest mammals and
      birds. The phylogenetic relationships among these suborders are unresolved
      despite decades of studies. We sequenced the mt genomes of eight species of
      parasitic lice and compared them with 17 other species of parasitic lice
      sequenced previously. We found that the typical single-chromosome mt genome is
      retained in the lice of birds but fragmented into many minichromosomes in the
      lice of eutherian mammals. The shared derived feature of mt genome fragmentation
      unites the eutherian mammal lice of Ischnocera (family Trichodectidae) with
      Anoplura and Rhynchophthirina to the exclusion of the bird lice of Ischnocera
      (family Philopteridae). The novel clade, namely Mitodivisia, is also supported by
      phylogenetic analysis of mt genome and cox1 gene sequences. Our results
      demonstrate, for the first time, that organelle genome fragmentation is
      informative for resolving controversial high-level phylogenies.

PMID- 30239979
TI  - Comment on: The multisystemic nature and natural history of joint hypermobility
      syndrome and Ehlers-Danlos syndrome in children: reply.

PMID- 30239980
TI  - Climatic niche comparison among ploidal levels in the classic autopolyploid
      system, Galax urceolata.
AB  - PREMISE OF THE STUDY: Autopolyploidy, or whole-genome duplication within a
      species, leads to closely related cytotypes in one geographic location. One
      hypothesized mechanism by which autopolyploids become established is climatic
      niche divergence from their diploid progenitor. Here we tested this hypothesis in
      diploid, triploid, and tetraploid Galax urceolata (Diapensiaceae) and predicted
      the effects of climate change on the relative distributions of these cytotypes.
      METHODS: We investigated whether climatic niche divergence has shaped the current
      distributions of Galax urceolata cytotypes in eastern North America using
      climatic niche modeling, multivariate analyses of environmental space, and
      geographic range analyses. We then projected the models of the three cytotypes
      onto an ensemble of future climate maps to determine how the distributions might
      be altered over time. KEY RESULTS: All cytotypes are geographically sympatric;
      however, climatic niche contraction and a slight niche shift of the tetraploids
      was observed relative to that of the diploids. Climate projections for all
      diploid and tetraploid cytotypes showed substantial range contraction without
      much, or any, range shift, suggesting that Galax urceolata will likely go extinct
      in nature as mountain refugia become warmer. CONCLUSIONS: Galax urceolata
      tetraploids occupy a slightly wetter habitat than that of their diploid
      progenitors. While we cannot take into account future adaptation, our models
      suggest extensive decreases in range distributions for both diploid and
      tetraploid G. urceolata based on climate change projections. Galax urceolata may
      therefore be under extreme threat due to loss of suitable habitat, and
      conservation efforts will be needed.

PMID- 30239981
TI  - Clinical, dermoscopic and reflectance confocal microscopy characterization of
      facial basal cell carcinomas presenting as small white lesions on sun-damaged
      skin.

PMID- 30239982
TI  - Patient and physician preferences for first-line treatment of classical Hodgkin
      lymphoma in Germany, France and the United Kingdom.
AB  - First-line treatments for classical Hodgkin lymphoma (HL) include ABVD
      (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPPescalated (escalated
      dose bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine,
      procarbazine, prednisone). To further improve overall outcomes, positron emission
      tomography-driven strategies and ABVD or BEACOPP variants incorporating the
      antibody-drug conjugate brentuximab vedotin (BV) or anti-PD1 antibodies are under
      investigation in advanced-stage patients. The present study aimed to elicit
      preferences for attributes associated with ABVD, BEACOPPescalated and BV-AVD (BV,
      adriamycin, vinblastine and dacarbazine) among patients and physicians. Cross
      sectional online discrete choice experiments were administered to HL patients (n
      = 381) and haematologists/oncologists (n = 357) in France, Germany and the United
      Kingdom. Included attributes were progression-free survival (PFS), overall
      survival (OS), and the risk of neuropathy, lung damage, infertility and
      hospitalisation due to adverse events. Whereas 5-year PFS and OS were the most
      important treatment attributes to patients, the relative importance of each
      attribute and preference weights for each level varied among physicians according
      to the description of the hypothetical patient for whom treatment was
      recommended. PFS and OS most strongly influenced physicians' recommendations when
      considering young female patients who did not want children or young male
      patients. Infertility was more important to physicians' treatment decision than
      PFS when considering young women with unknown fertility preferences, whereas
      hospitalisations due to adverse events played the largest role in treatment
      decisions for older patients.

PMID- 30239983
TI  - The cake flap: a technique of serial excision in quadrants useful beyond
      congenital nevi.

PMID- 30239984
TI  - Development of the other-race effect in Malaysian-Chinese infants.
AB  - Little is known about how infants born and raised in a multiracial environment
      process own- and other-race faces. We investigated face recognition of 3- to 4
      month-old (N = 36) and 8- to 9-month-old (N = 38) Chinese infants from Kuala
      Lumpur, Malaysia, a population that is considered multiracial, using female and
      male faces that are of infants' own-race (Chinese), experienced other-race
      (Malay) and less experienced other-race (Caucasian-White). Three- to 4-month-olds
      recognized own-race female faces, whereas 8- to 9-month-olds also recognized
      experienced other-race female faces (Malay) in addition to own-race female faces
      (Chinese). Furthermore, infants from this population did not show recognition for
      male faces at any age. This contrasts with 8- to 9-month-old British-White
      infants (Tham, Bremner, & Hay, ), a group that is considered single-race, who
      recognized female and male own-race faces. It appears that for infants born and
      raised in a multiracial environment, there is a developmental shift from a female
      based own-race recognition advantage to a female-based own- and experienced other
      race advantage that may relate to infants' social and caregiving experiences.

PMID- 30239985
TI  - Plaque-like dermatofibroma with satellitosis in a young woman.

PMID- 30239986
TI  - Dynamic Transition Patterns in Acculturation Among Hispanic Adolescents.
AB  - Acculturation consists of multiple domains (i.e., cultural practices,
      identifications, and values). However, less is known about how acculturation
      processes influence each other across multiple domains of acculturation. This
      study was designed to investigate transition patterns of acculturative processes
      within and across domains in a sample of 302 recent-immigrant Hispanic
      adolescents, Mage (SD) = 14.51 years (0.88) at baseline; male = 53%). Adolescents
      were assessed six times over a 3-year period. Latent profile analyses identified
      two profiles (high [or increasing] vs. low) for each domain at each timepoint. We
      found largely stable transition patterns in each domain over six timepoints.
      Importantly, sequential associations among profiles in acculturation domains were
      also detected. Implication for acculturation theory and research are discussed.

PMID- 30239987
TI  - Cultural value mismatch in urbanizing China: A large-scale analysis of
      collectivism and happiness based on social media and nationwide survey.
AB  - Throughout history, collectivism has contributed much to social bonding and human
      wellness. However, it remains unclear whether the collectivism-wellness equation
      still applies, when there is a mismatch between the collectivistic values and the
      ecological environment of urbanisation. Testing the hypothesis of cultural value
      mismatch (e.g., high urbanised & high collectivistic, or low urbanised & low
      collectivistic), two studies were designed to examine the relationship between
      collectivism and emotional wellbeing in China, with urbanisation as moderator.
      Based on the emotion analysis of tweets among 1.6 millions of Weibo users, Study
      1 found that the province-level collectivism scores were significantly and
      positively related to negative emotions in high urbanised provinces, but this
      relationship was not significant in low or middle urbanised provinces. Using a
      nationwide survey dataset, Study 2 showed that, on the individual level, those
      with higher collectivism reported less negative emotions, but only in low- and
      middle-urbanised provinces, not in high-urbanised provinces. On positive emotions
      in all areas, the positive effect of collectivism was observed on individual
      level, but not on province level. These findings support the value mismatch
      hypothesis of urbanisation, suggesting that the purchasing power of collectivism
      on wellbeing is compromised in urbanising China.

PMID- 30239988
TI  - The Burden of Sinusitis in Hematologic Transplant Patients: A National
      Perspective.
AB  - OBJECTIVES/HYPOTHESIS: To determine the impact of sinusitis on outcomes of
      hematologic transplant procedures. STUDY DESIGN: Retrospective analysis of a
      national hospital database. METHODS: The National Inpatient Sample database for
      2012 to 2013 was queried using International Classification of Diseases, Ninth
      Revision, Clinical Modification codes to identify patients undergoing hematologic
      transplants. Patients were divided based upon the presence or absence of a
      concomitant diagnosis of acute or chronic sinusitis. Patient demographics,
      clinical characteristics, discharge results, lengths of stay (LOS), and costs
      were compared between groups. RESULTS: There were 7,069 hematologic transplant
      cases identified, 2.7% of which had a diagnosis of sinusitis. Sinusitis patients
      had a longer LOS after transplant (24.9 +/- 15.9 days vs. 19.1 +/- 17.4 days, P <
      .001) and higher total hospital charges ($487,941 +/- $447,532 vs. $322,300 +/-
      $369,596, P < .001) than nonsinusitis patients. There was no difference in
      mortality between the two groups (P = .75). The 23 (12%) sinusitis patients who
      underwent sinus procedures had a longer LOS after transplant (34.8 +/- 25 days
      vs. 23.5 +/- 13.7 days, P = .001) and higher total hospital charges ($857,891 +/-
      $718,456 vs. $437,293 +/- $372,075, P < .001) than sinusitis patients without
      sinus procedures. Linear regression showed that sinusitis patients had excess LOS
      after transplant of 2.442 days and cost of $82,000.098. CONCLUSIONS: This study
      demonstrates that presence of sinusitis in patients undergoing hematologic
      transplant is associated with increased LOS and higher total hospital charges.
      Increased focus on diagnosis and if possible treatment of sinusitis prior to
      admission for transplantation may help reduce the impact of sinusitis after
      hematologic transplant. LEVEL OF EVIDENCE: NA Laryngoscope, 2018.

PMID- 30239989
TI  - Neighborhood Characteristics, Maternal Parenting, and Health and Development of
      Children from Socioeconomically Disadvantaged Families.
AB  - The present study examined the direct and indirect effects of neighborhood
      conditions on the health and development of children from socioeconomically
      disadvantaged families. Two waves of data were analyzed from the Fragile Families
      and Child Wellbeing study and its subsample of 3,656 mothers and their young
      children at ages 3 and 5. The results show that social cohesion was directly and
      indirectly associated with children's behavioral problems and health status.
      Social control was found to have an indirect effect on children's behavioral
      problems and cognitive development transmitted through maternal parenting quality
      and parenting stress. There were significant direct effects of neighborhood
      physical disorder on children's behavioral problems and cognitive development. In
      terms of effect size, mothers' parenting stress and parenting quality, economic
      hardship, education level, and health care coverage were also prominent factors
      in determining the health and development of children. Implications for
      interventions and future research are discussed.

PMID- 30239991
TI  - Within Our Skin.
AB  - From "beauty is only skin deep" to "it takes a thick skin," there are a countless
      number of skin-related aphorisms that serve as social commentaries on the beauty
      and resilience of skin. The skin as an interface to society may have diverse
      psychological implications, but its physiological importance to health is
      undeniable. As the largest organ in the body, the skin presents a formidable
      barrier that serves to protect our internal physiology from potentially harmful
      stimuli of the external environment.

PMID- 30239995
TI  - Erratum: Efficacy of the neurokinin-1 receptor antagonist rolapitant in
      preventing nausea and vomiting in patients receiving carboplatin-based
      chemotherapy.

PMID- 30239993
TI  - CORRIGENDUM: Implementing Pharmacogenomics in Europe: Design and Implementation
      Strategy of the Ubiquitous Pharmacogenomics Consortium.

PMID- 30239996
TI  - Stressful Life Events and Physical and Psychological Health: Mediating Effects of
      Differentiation of Self in a Spanish Sample.
AB  - The pathways between differentiation of self and health remain only partly
      elucidated. This cross-cultural study sought to test Bowen's hypothesis about the
      associations between differentiation, stressful life events, and physical and
      psychological health, in a sample of 466 Spanish adults. Results show that people
      with higher levels of differentiation were less prone to physical ailments (e.g.,
      heart disease, cancer, or blood disorders) and psychological symptoms (e.g.,
      depression or anxiety). Further, differentiation mediated the association between
      stress (i.e., perceived negativity of stress in the past year and number of
      stressful events across the lifetime) and physical and psychological health. The
      current research provides cross-cultural empirical evidence for the links between
      differentiation and mind and body health in a Mediterranean culture.

PMID- 30239997
TI  - Long-term imaging follow-up of a conservatively managed presumptive osseous
      cervical stenotic myelopathy in a puppy.

PMID- 30239998
TI  - Nurses' perceived spiritual climate of a hospital in Saudi Arabia.
AB  - AIM: This study investigated the spiritual climate of a hospital in Saudi Arabia
      as perceived by nurses. BACKGROUND: A spiritually conducive environment improves
      patient, nurse and organizational outcomes. Despite being important, no studies
      have investigated this area in the Muslim-dominated Middle Eastern countries.
      INTRODUCTION: A snapshot on the degree of spiritual climate perception may
      provide insight into the aspects that may need improvement and may become basis
      for the creation of health and nursing policies directed towards creating a
      spiritually-accepting and respecting clinical workplace. METHOD: A sample of 219
      nurses employed in a 500-bed capacity hospital in Saudi Arabia was included in
      this cross-sectional study utilizing the spiritual climate scale. RESULTS: The
      nurses perceived their hospital's spiritual climate to be fair. The item 'I am
      encouraged to express spirituality in this clinical area' received the lowest
      mean, whereas the item 'My spiritual views are respected in this clinical area'
      received the highest mean. Being Saudi, having less total experience as a nurse,
      and having greater total experience as a nurse in Saudi Arabia and in the present
      hospital positively influenced the perception of the spiritual climate among
      nurses. CONCLUSION: The findings stress the need to improve the spiritual climate
      in the hospital. IMPLICATIONS FOR NURSING AND NURSING POLICY: Hospitals are
      recommended to create policies to implement interventions geared towards creating
      a spiritually-friendly environment. Hospitals are encouraged to create a safe
      place where nurses can freely express their spirituality regardless of preference
      or religious denomination. Spiritual education may be provided by hospitals as
      part of continuing education. Managers may also focus on the existential
      spirituality of nurses, especially for spiritually-sensitive environments such as
      Saudi Arabia.

PMID- 30239999
TI  - Tuning the Triplet-Triplet Energy Transfer Between Phthalocyanine and Carotenoid
      by Methyl Groups on the Conjugated Chain.
AB  - Mimicking light-harvesting and photoprotective processes of natural
      photosynthesis by artificial supramolecular systems is of considerable interest
      for artificial photosynthesis. The authors of the highlighted paper report on
      synthesis and spectroscopic characterization of a novel Pd-phthalocyanine
      carotenoid dyads that allow to directly follow the triplet-triplet energy
      transfer between Pd-phthalocyanine and carotenoid. Unexpectedly, the T-T energy
      transfer does not follow the dependence on conjugation length of the acceptor
      carotenoid. Instead, the donor-acceptor coupling and resulting T-T energy
      transfer rate is controlled by the presence or absence of a methyl groups on the
      conjugated chain in the vicinity of the carotenoid keto-oxygen. This reveals yet
      another level of tuning the spectroscopic properties of carotenoids having a
      conjugated keto group in their structure, underlining their potential for
      tailoring specific supramolecular complexes carrying out either light-harvesting
      or photoprotective functions.

PMID- 30240000
TI  - Predictive modeling of housing instability and homelessness in the Veterans
      Health Administration.
AB  - OBJECTIVE: To develop and test predictive models of housing instability and
      homelessness based on responses to a brief screening instrument administered
      throughout the Veterans Health Administration (VHA). DATA SOURCES/STUDY SETTING:
      Electronic medical record data from 5.8 million Veterans who responded to the
      VHA's Homelessness Screening Clinical Reminder (HSCR) between October 2012 and
      September 2015. STUDY DESIGN: We randomly selected 80% of Veterans in our sample
      to develop predictive models. We evaluated the performance of both logistic
      regression and random forests-a machine learning algorithm-using the remaining
      20% of cases. DATA COLLECTION/EXTRACTION METHODS: Data were extracted from two
      sources: VHA's Corporate Data Warehouse and National Homeless Registry. PRINCIPAL
      FINDINGS: Performance for all models was acceptable or better. Random forests
      models were more sensitive in predicting housing instability and homelessness
      than logistic regression, but less specific in predicting housing instability.
      Rates of positive screens for both outcomes were highest among Veterans in the
      top strata of model-predicted risk. CONCLUSIONS: Predictive models based on
      medical record data can identify Veterans likely to report housing instability
      and homelessness, making the HSCR screening process more efficient and informing
      new engagement strategies. Our findings have implications for similar instruments
      in other health care systems.

PMID- 30240001
TI  - Practical implementation of the planar and spatial rotator in a complex tissue:
      the brain.
AB  - : In neuroscience, application of widely used stereological local volume
      estimators, including the planar rotator, is challenged by the combination of a
      complex tissue organisation and an estimator requirement of either isotropic or
      vertical sections, i.e. randomly oriented tissue. The spatial rotator is
      applicable with any tissue orientation but is sensitive to projection artefacts.
      The challenge is thus to select the most appropriate method for individual
      analyses. In this study, agreement between estimates of mean cell volume acquired
      with the vertical planar and the spatial rotator is assessed for two brain
      regions with different types of cytoarchitecture (motor cortex and hippocampal
      cornu ammonis 1). The possibility of using the planar rotator in tissues cut in
      an arbitrary direction is explored and requirements for a theoretically unbiased
      result as well as histological considerations are provided. LAY DESCRIPTION:
      Cells may change volume both during disease and with advancing age. Assessment of
      the volume of individual cells can therefore serve as a useful indicator of
      general tissue state. Most available methods to estimate cell volume in tissue
      sections, however, require that the tissue analysed has random orientation.
      Particularly for complex tissues such as the brain this is a challenge as
      identification, delineation and subdivision of many brain areas rely heavily on
      the use of anatomical atlases where illustrations depict the tissue in a few well
      known orientations. In this study, the practical application of two different
      methods for estimating mean cell volumes in tissues cut in a preferred
      orientation is evaluated. Requirements for the feasibility of cell volume
      estimation without random tissue orientation as well as histological
      considerations are provided.

PMID- 30240002
TI  - Ascorbic acid supplementation ameliorates testicular hormonal signaling, sperm
      production and oxidative stress in male rats exposed to rosuvastatin during pre
      puberty.
AB  - Dyslipidemias are occurring earlier in the population due to the augmentation of
      obesity. Rosuvastatin reduces cholesterol and triglycerides; however, previous
      studies have shown that it may affect male reproduction. Ascorbic acid (AA), an
      antioxidant compound, plays a protective role in the male reproductive system.
      This study aimed to evaluate whether pre-pubertal exposure to rosuvastatin may
      impair testicular structure and antioxidant status in male rats and if
      supplementation with AA may alleviate these damages. Male rats were randomly
      divided into six experimental groups (n = 10) on postnatal day (PND) 23 and
      received the different treatments by gavage from PND 23 to 53. The experimental
      groups received vehicle (saline solution 0.9%), 3 or 10 mg/kg/day of rosuvastatin
      diluted in saline solution 0.9%, supplementation with 150 mg/day of AA, 3
      mg/kg/day of rosuvastatin in association with 150 mg/day of AA or 10 mg/kg/day of
      rosuvastatin associated with 150 mg/day of AA. Testicular parameters were
      assessed on PND 53 and 110. There were diminished androgen receptors staining in
      the Sertoli cells and increased germ cell death in rosuvastatin-exposed groups,
      in both periods. Spermatids showed lower estrogen alpha-receptors staining in the
      group exposed to 10 mg of statin at adulthood. There were androgen depletion and
      increased lipid peroxidation and catalase activity in statin-exposed groups.
      Rosuvastatin exposure during pre-puberty impaired testicular structure, steroid
      receptor distribution and increased oxidative stress; however, AA was able to
      ameliorate the impairment provoked by statin exposure.

PMID- 30240003
TI  - Positive feedback loop of lncRNA LINC01296/miR-598/Twist1 promotes non-small cell
      lung cancer tumorigenesis.
AB  - Emerging evidence has illustrated the vital roles of long noncoding RNAs
      (lncRNAs) in human cancers. However, the role of lncRNAs in non-small cell lung
      cancer (NSCLC) is still elusive and poorly understood. In the current study, our
      team conducted extensive experiments to identify the role of long intergenic
      nonprotein coding (LINC01296) on NSCLC tumorigenesis. The results illustrated
      that the elevated LINC01296 expression in NSCLC tissue specimens and cell lines
      were closely correlated with the poor prognosis of patients with NSCLC.
      Functional studies revealed that LINC01296 knockdown silenced by small
      interfering RNAs inhibited proliferation, accelerated apoptosis in vitro, and
      impaired tumor growth in vivo. Mechanical studies showed that INC01296 harbored
      miR-598, acting as a microRNA "sponge." Besides, miR-598 targeted the 3'-UTR of
      Twist1. Interestingly, transcription factor Twist1 could bind with the promoter
      of INC01296 and activate its transcriptional level. In summary, we conclude that
      INC01296/miR-598/Twist1 constitutes a positive feedback loop to promote the
      tumorigenesis of NSCLC, providing a novel insight and a valuable therapeutic
      strategy.

PMID- 30240004
TI  - In vivo microscopic and optical coherence tomography classification of
      neurotrophic keratopathy.
AB  - Neurotrophic keratopathy (NK) is a rare degenerative corneal disorder
      characterized by instability of epithelial integrity with consequent epithelial
      defects that can worsen up to persistent epithelial defects with stromal melting
      and ulceration. The pathogenesis of NK springs from a variable degree of damage
      to the trigeminal nerve plexus, leading to a reduction or total loss of corneal
      sensitivity. Mackie classification (1995) distinguishes three stages of NK, based
      on the severity of clinical presentation. The technological innovations in
      corneal diagnostic imaging allow clinicians to accurately study the morphometry
      and morphology of corneal structure with microscopic resolution. In this study,
      45 patients affected by NK at different stages underwent in vivo confocal
      microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) with
      particular attention to analyze subbasal nerve plexus fibers and the stromal
      structure. At the light of IVCM and AS-OCT observations, we propose a different
      staging of NK with respect to the Mackie's classification that takes into account
      the severity of subbasal nerve fibers damage and the extension in depth of
      stromal ulceration; this classification better defines, at the time of diagnosis,
      the cellular and structural alterations in the affected corneas, with possible
      prognostic and therapeutic values in the management of NK.

PMID- 30240005
TI  - Role of Ser65, His148 and Thr203 in the Organic Solvent-dependent Spectral Shift
      in Green Fluorescent Protein.
AB  - The photophysics of green fluorescent protein (GFP) is remarkable because of its
      exceptional property of excited state proton transfer (ESPT) and the presence of
      a functional proton wire. Another interesting property of wild-type GFP is that
      its absorption and fluorescence excitation spectra are sensitive to the presence
      of polar organic solvents even at very low concentrations. Here, we use a
      combination of methodologies including site-specific mutagenesis, absorption
      spectroscopy, steady-state and time-resolved fluorescence measurements and all
      atom molecular dynamics simulations in explicit solvent, to uncover the mechanism
      behind the unique spectral sensitivity of GFP toward organic solvents. Based on
      the evidences provided herein, we suggest that organic solvent-induced changes in
      the proton wire prevent ground state movement of a proton through the wire and
      thus bring about the spectral changes observed. The present study can not only
      help to understand the mechanism of proton transfer by further dissecting the
      intricate steps in GFP photophysics but also encourages to develop GFP-based
      organic solvent biosensors.

PMID- 30240006
TI  - Glucocorticoids reduce chemotherapeutic effectiveness on OSCC cells via glucose
      dependent mechanisms.
AB  - Synthetic corticosteroids are routinely administered during the treatment of
      several diseases, including malignancies. However, recent evidence suggests that
      corticosteroids may have tumor-promoting effects, particularly in epithelial
      neoplasms. Our aim was to assess the role of the recently characterized cancer
      associated glucocorticoid (GC) system in the resistance to chemotherapy of oral
      malignant keratinocytes. Human malignant oral keratinocyte cell lines
      H314/H357/H400/BICR16/BICR56 were tested with: two chemotherapeutic agents,
      doxorubicin (DOXO) and 5-fluorouracil (5-FU), as well as hydrocortisone (HC),
      adrenocorticotropic hormone (ACTH), 5-pregnen-3-beta-ol-20-one-16-alfa
      carbonitrile (PCN), and two glucose uptake inhibitors, Fasentin and WZB. Both
      DOXO and 5-FU induced apoptosis in a dose-dependent and time-dependent manner. HC
      administration (100 nM) reduced the effectiveness of both chemotherapeutic agents
      to a variable extent in all 5 oral squamous cell carcinoma cell lines. ACTH also
      reduced the effectiveness of DOXO on 2 cell lines tested (H357 and BICR56). The
      glucose uptake inhibitors Fasentin and WZB were able to partially block the
      increased resistance to the cytotoxic drugs induced by HC. In summary, we have
      demonstrated, for the first time, the importance of cortisol on oral cancer cells
      ability to proliferate and combat the effectiveness of chemotherapeutic agents.
      This effect appears to be glucose dependent.

PMID- 30240007
TI  - Positioning the Health Services Research Workforce for Continued Success:
      Recommendations from AcademyHealth Stakeholders.
AB  - AcademyHealth established a Workforce Initiative Task Force in 2016 to conduct an
      assessment of the state of the health services research workforce and develop
      recommendations for its future in the context of the changing health care and
      research ecosystems. This assessment included four components: a series of
      commissioned papers, an online priority setting process, a multistakeholder
      summit, and final analysis by the AcademyHealth Education Council. This paper
      presents this process and the resultant list of prioritized recommendations and
      planned next steps.

PMID- 30240008
TI  - Understanding the Current Health Services Research Workforce and Maximizing its
      Future.
AB  - In 2016, AcademyHealth continued its longstanding efforts to understand the
      health services research (HSR) workforce, to inform its changing needs through
      the commissioning of several papers and an invitational conference. This paper
      serves to summarize the commissioned studies that appear in the current issue of
      this journal.

PMID- 30240009
TI  - Show Me the Money! Trends in Funding for Health Services Research.
AB  - This paper presents longitudinal data representing federal funding for health
      services research and discusses the observed trends in the larger context of
      overall funding for research and development in the United States. By putting
      into context public and private funding trends, the authors examine how these
      trends effect the supply and demand of the health services research workforce.

PMID- 30240010
TI  - Are We Growing the Right Health Services Research Workforce of the Future?
      Thoughts from a National Delivery System.

PMID- 30240012
TI  - Editorial.

PMID- 30240011
TI  - Noninvasive three-dimensional power Doppler imaging for the assessment of acute
      cerebral blood flow alteration in a mouse model of subarachnoid haemorrhage.
AB  - We aimed to evaluate the feasibility of a noninvasive method of cerebral blood
      flow (CBF) measurement using high-frequency power Doppler ultrasound imaging in a
      mouse model of subarachnoid haemorrhage (SAH). The 3-dimensionally (3D)
      reconstructed blood flow signals (%vascularity) within the brain volume of the
      middle cerebral artery territory correlated well with reference parameters,
      baseline carotid artery blood flow (r2 = 0.52, P < 0.0001) and normalized CBF
      changes (r2 = 0.74 P < 0.0001). These data suggest that the 3D power Doppler
      analysis may have potential for reflecting real-time CBF changes during the acute
      phase of experimental SAH, which may be applicable to preclinical studies on
      early brain injury. This article is protected by copyright. All rights reserved.

PMID- 30240013
TI  - Issue Information - Page.

PMID- 30240014
TI  - In pursuit of job satisfaction and happiness: Testing the interactive
      contribution of emotion-regulation ability and workplace social support.
AB  - The present study focuses on the interplay of emotion-regulation ability and
      perceived workplace social support as predictors of job satisfaction and
      happiness in a Spanish multi-occupational sample. A total of 494 working adults
      (39.4% females) took part in this study. Emotion-regulation ability and perceived
      support from colleagues and supervisors were positively associated. In addition,
      emotion-regulation ability and perceived support from colleagues and supervisors
      showed positive associations with job satisfaction and happiness. Furthermore,
      considering results from moderation analyses, when low levels of perceived
      workplace social support were reported, the relationship between emotion
      regulation and both job satisfaction and happiness was stronger than in cases of
      higher perceived workplace support. In line with previous studies, these findings
      suggest that training in emotion regulation abilities may take into consideration
      the potential moderating role of job characteristics such as support from
      colleagues and supervisors. Finally, theoretical and practical implications of
      the joint study of these factors in line with the Job Demands-Resources model and
      the Emotional Intelligence framework are discussed.

PMID- 30240016
TI  - Phytochemistry Profile, Nutritional Properties and Pharmacological Activities of
      Mauritia flexuosa.
AB  - Mauritia flexuosa L. (Arecaceae) is a popular Brazilian fruit known as "buriti"
      and belonging to the category of functional foods. This work reviewed the
      phytochemistry profile, nutritional and pharmacological activities of M.
      flexuosa. The main bioactive compounds reported to buriti were carotenoids,
      tocopherols, ascorbic acid, phenolic compounds, fiber, phytosterols, and mono-
      and poly-unsaturated fatty acids. These compounds were mainly related to
      antioxidant, hypolipemiant, photoprotector, antiaggregant, antithrombotic, anti
      inflammatory, hypoglycemiant, antimicrobial, and antitumor activities.
      Furthermore, some compounds present in buriti fruit and its properties were
      tested in vitro and in vivo and showed biotechnology applications, especially for
      extraction of fiber, polysaccharides, pigments, antioxidants, and oil. Howerer,
      the buriti fruit shows great relevance to the development of new products in
      food, pharmaceutical and chemical industry, this fruit is still underexploited
      and it has need to expand its production chain and processing to encourage their
      consumption and utilization.

PMID- 30240017
TI  - Medicalisation, pharmaceuticalisation, or both? Exploring the medical management
      of sleeplessness as insomnia.
AB  - In this paper we examine the medical management of sleeplessness as 'insomnia',
      through the eyes of general practitioners (GPs) and sleep experts in Britain.
      Three key themes were evident in the data. These related to (i) institutional
      issues around advocacy and training in sleep medicine (ii) conceptual issues in
      the diagnosis of insomnia (iii) and how these played out in terms of treatment
      issues. As a result, the bulk of medical management occurred at the primary
      rather than secondary care level. These issues are then reflected on in terms of
      the light they shed on relations between the medicalisation and the
      pharmaceuticalisation of sleeplessness as insomnia. Sleeplessness, we suggest, is
      only partially and problematically medicalised as insomnia to date at the
      conceptual, institutional and interactional levels owing to the foregoing
      factors. Much of this moreover, on closer inspection, is arguably better captured
      through recourse to pharmaceuticalisation, including countervailing moves and
      downward regulatory pressures which suggest a possible degree of
      depharmaceuticalisation in future, at least as far prescription hypnotics are
      concerned. Pharmaceuticalisation therefore, we conclude, has distinct analytical
      value in directing our attention, in this particular case, to important dynamics
      occurring within if not beyond the medicalisation of sleeplessness as insomnia.

PMID- 30240018
TI  - p53-Dependent and p53-Independent Responses of Cells Challenged by
      Photosensitization.
AB  - The p53 protein exerts fundamental roles in cell responses to a variety of stress
      stimuli. It has clear roles in controlling cell cycle, triggering apoptosis,
      activating autophagy and modulating DNA damage response. Little is known about
      the role of p53 in autophagy-associated cell death, which can be induced by
      photoactivation of photosensitizers within cells. The photosensitizer 1,9
      dimethyl methylene blue (DMMB) within nanomolar concentration regimes has
      specific intracellular targets (mitochondria and lysosomes), photoinducing a
      typical scenario of cell death with autophagy. Importantly, in consequence of its
      subcellular localization, photoactive DMMB induces selective damage to
      mitochondrial DNA, saving nuclear DNA. By challenging cells having different p53
      protein levels, we investigated whether p53 modulates DMMB/light-induced
      phototoxicity and cell cycle dynamics. Cells lacking p53 activity were slightly
      more resistant to photoactivated DMMB, which was correlated with a smaller sub-G1
      population, indicative of a lower level of apoptosis. DMMB photosensitization
      seems to induce mostly autophagy-associated cell death and S-phase cell cycle
      arrest with replication stress. Remarkably, these responses were independent on
      the p53 status, indicating that p53 is not involved in either process. Despite
      describing some p53-related responses in cells challenged by photosensitization,
      our results also provide novel information on the consequences of DMMB
      phototoxicity.

PMID- 30240019
TI  - Retraction.
AB  - Calvo-Guirado JL, Delgado Ruiz RA, Ramirez-Fernandez MP, Abboud M, Janjic B, Mate
      Sanchez de Val JE. Histological and histomorphometric analyses of narrow
      implants, crestal and subcrestally placed in severe alveolar atrophy: a study in
      foxhound dogs. Clin Oral Impl Res. 2016;27: 497-504. The above article, published
      online on 9 February 2015 in Wiley Online Library (wileyonlinelibrary.com), and
      in Volume 27, pp. 497-504, has been retracted by agreement between the journal
      Editor in Chief, L Heitz-Mayfield, and John Wiley & Sons Ltd. The retraction has
      been agreed due to image discrepancies, resulting in unreliable data. Images in
      Figures 1a, 1b, 2a and 2b have been used in another publication representing
      different materials. Reference Calvo-Guirado JL, Delgado Ruiz RA, Ramirez
      Fernandez MP, Abboud M., Janjic B, Mate Sanchez de Val JE. Histological and
      histomorphometric analyses of narrow implants, crestal and subcrestally placed in
      severe alveolar atrophy: a study in foxhound dogs. Clin Oral Impl Res. 2016;27:
      497-504. https://doi.org/10.1111/clr.12569.

PMID- 30240021
TI  - Issue Information - Page.

PMID- 30240020
TI  - The histological absence of IgG4 positive plasma cells in juvenile
      xanthogranuloma; comments on 'Systemic juvenile xanthogranuloma: a case report
      and brief review'.

PMID- 30240022
TI  - Acute inhalation co-exposure to 1,2-dichloropropane and dichloromethane cause
      liver damage by inhibiting mitochondrial respiration and defense ability in mice.
AB  - 1,2-Dichloropropane (1,2-DCP) is used as an industrial solvent, insecticide
      fumigant and household dry cleaning product. Carcinogenicity caused by long-term
      exposure to 1,2-DCP is well established. However, the possible liver damage and
      related toxic mechanisms associated with acute inhalation exposure to 1,2-DCP are
      rarely reported. In this study, we investigated the effects of individual and
      combined exposure to 1,2-DCP and dichloromethane (DCM) on mice liver. The results
      showed that 1,2-DCP significantly caused liver necrosis, possibly due to 1,2-DCP
      induced inhibition of the mitochondrial respiratory chain complex I-IV
      activities, resulting in mitochondrial dysfunction and extreme ATP consumption.
      Moreover, 1,2-DCP also decreased mitochondrial defense ability by inhibiting the
      mitochondrial glutathione S-transferase 1 (MGST1) activity, further aggravating
      liver damage. Additionally, we found that DCM co-exposure potentially enhanced
      1,2-DCP toxicity. Our findings suggest that inhibition of mitochondrial function
      and MGST1 activity play critical roles in modulating 1,2-DCP-induced liver
      damage. Furthermore, our results contribute to study the new mechanism of
      mitochondria-dominated signaling pathways underlying liver injury induced by 1,2
      DCP and DCM.

PMID- 30240023
TI  - Complete genome sequence of soil actinobacteria Streptomyces cavourensis TJ430.
AB  - A new actinobacteria Streptomyces cavourensis TJ430 was isolated from the
      mountain soil collected from the southwest of China. In previous study, TJ430
      showed striking bactericidal activities and strong ability of antibiotic
      production. Here, we report complete genome of this bacterium, consisting of 7.6
      Mb linear chromosome and 0.2 Mb plasmids. It was predicted 6450 genes in
      chromosome and 225 genes in plasmids, as well as 12 gene islands in chromosome.
      Abundant genes have predicted functions in antibiotic metabolism and stress
      resistance. A whole-genome comparison of S. cavourensis TJ430, S. coelicolor
      A3(2), and S. lividans 66 indicates that TJ430 has a relatively high degree of
      strain specificity. The 16S rRNA phylogenetic tree shows the high identities
      (99.79%) of TJ430 with S. cavourensis DSM40300. TJ430 is a new and rare
      Streptomyces species, and analysis of its genome helps us to better understand
      primary metabolism mechanism of this isolate, as well as the evolutionary
      biology.

PMID- 30240024
TI  - Pain relief following a single-dose intra-articular injection of
      methylprednisolone in the temporomandibular joint arthralgia-A multicentre
      randomised controlled trial.
AB  - BACKGROUND: Temporomandibular joint (TMJ) arthralgia is a painful condition
      assumed to be associated with local inflammation. OBJECTIVE: The objective of the
      present study was to determine the efficacy for reducing pain of a single-dose
      intra-articular (IA) injection of methylprednisolone to the TMJ. The hypothesis
      was that methylprednisolone would effectively reduce TMJ pain. METHODS: This
      randomised, double-blind, parallel-group, multicentre, controlled study included
      visits for enrolment, treatment and 4-week follow-up. The study included patients
      18 years and older who had been diagnosed with unilateral TMJ arthralgia. All
      participants were randomly assigned to receive 1 mL IA injections of
      methylprednisolone or saline. The primary outcome was change in recorded pain
      intensity on a visual analogue scale (VAS) at maximum jaw opening, analysed in
      the per protocol population. RESULTS: In total, 54 patients were randomly
      assigned to single-dose IA injections with methylprednisolone (n = 27) or saline
      (n = 27). Between baseline and the 4-week follow-up, VAS-rated pain intensity at
      maximum jaw opening decreased from a mean of 61.0 (95% confidence interval [CI]:
      50.1; 70.7) to 33.9 (95% CI: 21.6; 46.2) in the methylprednisolone group and from
      59.6 (95% CI: 50.7; 65.9) to 33.9 (95% CI: 23.8; 43.9) in the saline group. The
      between-group difference was not significant (P = 0.812). Treatment-related
      adverse events were doubled in the methylprednisolone group. CONCLUSION:
      Methylprednisolone provided no additional benefit for reducing pain, but caused
      more harm compared with saline following a single-dose IA injection in patients
      with TMJ arthralgia.

PMID- 30240025
TI  - Retraction.
AB  - Calvo-Guirado JL, Mate-Sanchez JE, Delgado-Ruiz RA, Romanos GE, De Aza-Moya P,
      Velazquez P. Bone neo-formation and mineral degradation of 4Bone.(r) Part II:
      histological and histomorphometric analysis in critical size defects in rabbits.
      Clin Oral Impl Res. 2015;26: 1402-1406. The above article, published online on 28
      August 2014 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 26,
      pp. 1402-1406, has been retracted by agreement between the journal Editor in
      Chief, L Heitz-Mayfield, and John Wiley & Sons Ltd. The retraction has been
      agreed due to image discrepancies, resulting in unreliable data. Images in Figure
      2c have been used in another publication representing different time points and
      materials. Reference Calvo-Guirado JL, Mate-Sanchez JE, Delgado-Ruiz RA, Romanos
      GE, De Aza-Moya P, Velazquez P. Bone neo-formation and mineral degradation of
      4Bone.(r) Part II: histological and histomorphometric analysis in critical size
      defects in rabbits. Clin Oral Impl Res. 2015;26: 1402-1406.
      https://doi.org/10.1111/clr.12465.

PMID- 30240026
TI  - NanoDCFH-DA: A Silica-based Nanostructured Fluorogenic Probe for the Detection of
      Reactive Oxygen Species.
AB  - A biocompatible fluorescent nanoprobe for the detection of reactive oxygen
      species in biological systems has been designed, synthesized and characterized,
      circumventing some of the limitations of the molecular probe diacetyl 2',7'
      dichlorodihydrofluorescein (DCFH-DA). It has been synthetized the nanoparticulate
      form of DCFH-DA by covalently attaching the widely used fluorescent probe DCFH-DA
      to a mesoporous silica nanoparticle through a linker. The reactivity of nanoDCFH
      DA has been tested toward several reactive oxygen species. In addition, it has
      been proved to slow down DCFH-DA reaction with molecular oxygen and it hampers
      from interactions with proteins. As a final piece of evidence, in vitro studies
      showed that the nanoprobe is internalized by HeLa cancer cells, thus being
      capable of detecting intracellularly generated reactive oxygen species. To sum
      up, it can be stated that nanoDCFH-DA overcomes two major problems of free DCFH
      DA, namely oxidation of the probe by air and interaction with proteins in
      biological systems. This "nano" approach has thus proven useful to extend the
      utility of an existing and valuable fluorescent probe to complex biological
      systems.

PMID- 30240028
TI  - Increased autumn productivity permits temperate trees to compensate for spring
      frost damage.
AB  - Climate warming is leading to earlier budburst and therefore an increased risk of
      spring frost injury to young leaves. But to what extent are second-cohort leaves,
      which trees put out after leaf-killing frosts, able to compensate incurred
      losses? To investigate whether second-cohort leaves behave differently from first
      cohort leaves, we exposed saplings of beech (Fagus sylvatica), oak (Quercus
      robur), and honeysuckle (Lonicera xylosteum) to experimental treatments mimicking
      either a warm spring or a warm spring with a leaf-killing frost. Refoliation took
      48, 43, and 36 d for beech, oak and honeysuckle, respectively. In beech and oak,
      autumn Chl content and photosynthesis rates were higher in second- than in first
      cohort leaves, senescence in second-cohort leaves occurred c. 2-wk-later, and
      autumn bud growth in beech was elevated 66% in frost-damaged plants compared with
      the warm spring treatment. No differences in autumn phenology and growth were
      observed for honeysuckle. Overall, in beech and oak, delayed Chl breakdown in
      second-cohort leaves mitigated 31% and 25%, respectively, of the deficit in
      growing-season length incurred by spring frost damage. These results reveal an
      unexpected ability of second-cohort leaves of beech and oak to compensate for
      spring frost damage, and demonstrate that long-lived trees vary their autumnal
      phenology depending on preceding productivity.

PMID- 30240027
TI  - Imaging phosphodiesterase-10a availability in cocaine use disorder with [11
      C]IMA107 and PET.
AB  - Phosphodiesterase-10a (PDE10a) is located exclusively in medium spiny neurons
      (MSN). Rodent studies show an increase in striatal MSN spine density following
      exposure to cocaine. These increases in MSN spine density are suggested to
      underlie neurobiological changes which contribute to cocaine self-administration.
      No postmortem or imaging studies have confirmed this finding in humans. Here, we
      hypothesized an increase in the MSN marker PDE10a in subjects with cocaine use
      disorder ("cocaine users") compared to controls. PDE10a availability was measured
      with [11 C]IMA107 and positron emission tomography in 15 cocaine users and 15
      controls matched for age, gender, and nicotine status. Cocaine users with no
      comorbid psychiatric, medical, or drug abuse disorders were scanned following two
      weeks of outpatient-monitored abstinence. [11 C]IMA107 binding potential relative
      to nondisplaceable uptake (BPND ) in the regions of interest was derived with the
      simplified reference tissue method. No significant effect of diagnosis on BPND
      was demonstrated using linear mixed modeling with [11 C]IMA107 BPND as the
      dependent variable and regions of interest as a repeated measure. There were no
      significant relationships between BPND and clinical rating scales. To the extent
      that PDE10a is a valid proxy for MSN spine density, these results do not support
      its increase in recently abstinent cocaine users.

PMID- 30240030
TI  - Thinking About the Opposite of What Is Said: Counterfactual Conditionals and
      Symbolic or Alternate Simulations of Negation.
AB  - When people understand a counterfactual such as "if the flowers had been roses,
      the trees would have been orange trees," they think about the conjecture, "there
      were roses and orange trees," and they also think about its opposite, the
      presupposed facts. We test whether people think about the opposite by
      representing alternates, for example, "poppies and apple trees," or whether
      models can contain symbols, for example, "no roses and no orange trees." We
      report the discovery of an inference-to-alternates effect-a tendency to make an
      affirmative inference that refers to an alternate even from a negative minor
      premise, for example, "there were no orange trees, therefore there were poppies."
      Nine experiments show the inference-to-alternates effect occurs in a binary
      context, but not a multiple context, and for direct and indirect reference; it
      can be induced and reduced by prior experience with similar inferences, and it
      also occurs for indicative conditionals. The results have implications for
      theories of counterfactual conditionals, and of negation.

PMID- 30240029
TI  - Aldosterone-producing adrenocortical carcinoma with myxoid differentiation in a
      cat.
AB  - A 10-year-old male neutered Persian cat was presented with an abdominal mass and
      history of weakness. Blood smear examination found marked elliptocytosis, and
      serum biochemical analysis revealed hypokalemia, hypochloremia, increased
      creatine kinase activity, and a high aldosterone concentration. Cytologic
      examination of the mass revealed neoplastic endocrine cells with moderate
      criteria of malignancy, favoring adrenocortical neoplasia. The adrenal mass was
      surgically excised and histologically characterized by lobules of mildly
      pleomorphic, polygonal neoplastic cells with moderate to abundant, occasionally
      granular, eosinophilic cytoplasm. Lobules were separated by fine fibrovascular
      trabeculae, and numerous cystic cavities containing amorphous eosinophilic
      material that stained positive with Alcian blue and periodic acid-Schiff were
      seen. Neoplastic cells were multifocally positive for cytochrome P450 aldosterone
      synthase. Based on clinicopathologic and immunohistochemical findings the present
      case was diagnosed as an aldosterone-producing adrenocortical carcinoma with
      myxoid differentiation. While this entity has not been reported in cats, myxoid
      differentiation of adrenocortical carcinomas has been found in other species and
      can pose a major diagnostic challenge on microscopic examination.

PMID- 30240031
TI  - The controversy of complete lymph node dissection; reply to 'Completion
      lymphadenectomy should not necessarily be recommended after a positive SLN
      biopsy'.

PMID- 30240032
TI  - Development of a Novel Computerized Clinical Decision Support System to Improve
      Adolescent Sexual Health Care Provision.
AB  - OBJECTIVE: The objective was to develop an acceptable clinical decision support
      (CDS) system to facilitate evidence-based sexual health care for adolescents in
      the emergency department (ED). METHODS: In this multiphased iterative process, we
      engaged an expert group to synthesize evidence on a wide range of sexual health
      services (e.g., contraception, condoms, identification and treatment of
      previously diagnosed sexually transmitted infection). We created a computerized
      questionnaire and embedded our decision tree, utilizing patient-entered responses
      to create tailored, evidence-based recommendations, and embedded links to study
      related resources such as the emergency contraception (EC) quick guide. We
      utilized mixed methodology to explore perspectives of adolescents aged 14 to 19
      years and clinicians at two general and two pediatric EDs after they interacted
      with the system. Clinicians reported usefulness (Likert scale 1 = not at all, 4 =
      very); adolescents reported acceptability. We used the chi-square test to compare
      responses between subgroups. We collected adolescents' verbatim responses to open
      ended questions; clinicians self-entered responses. Four authors independently
      generated themes from qualitative responses before compiling key findings and
      achieving consensus on final themes. RESULTS: Among 57 clinicians (23 physicians,
      23 nurses, 11 nurse practitioners; 54% female; 65% aged < 40 years), the mean
      system usefulness rating was 3.4 +/- 0.7. Sex, age, clinician role, or ED type
      were not associated with rating the system "somewhat/very" useful. Clinicians
      identified barriers (e.g., time constraints) that could be overcome by
      implementation considerations (e.g., training) as well as benefits including
      improved care. For future assessments, providers preferred computer (65%) over
      face-to-face interview (26%). Among 57 adolescents (mean age = 16.2 years; 75%
      female; 56% sexually experienced), nearly all (95%) reported that it was
      "very/somewhat easy" to complete the computerized questionnaire and to understand
      the questions. Most adolescents understood the EC quick guide and correctly
      identified that ulipristal, compared to levonorgestrel, required a prescription
      and was more effective. For future assessments, adolescents preferred computer
      (69%) over face-to-face interviews (9%). CONCLUSIONS: We developed a sexual
      health CDS system that is easy to use and can facilitate evidence-based care to
      reduce health outcome gaps. Evaluation of system impact on service delivery and,
      ultimately, health outcomes is needed.

PMID- 30240033
TI  - Influence of environmental and genetic factors on 3-hydoxypropionaldehyde
      production by Lactobacillus reuteri.
AB  - The influence of environmental factors such as glycerol concentration, time of
      production, presence of Escherichia coli, and two different strains of
      Lactobacillus reuteri (ATCC 55730 and ATCC 53608) on 3-hydroxypropionaldehyde (3
      HPA) production was analyzed. Additionally, the influence of those factors on
      gene expression in the 3-HPA production pathway was evaluated. The genes studied
      were GldC, cbiP, and Lreu_1734. The results of this study showed that the
      principal environmental factors that influence 3-HPA production are glycerol
      concentration and Lactobacillus reuteri strain. As glycerol concentration
      increased, 3-HPA content increased. The greatest 3-HPA concentration (56.6 mM +/
      5.99) was achieved by L. reuteri ATCC 55730. Gene expression was also affected by
      environmental factors. Factor that showed the greatest influence were also strain
      and glycerol concentration. The genes cbiP, GldC, and Lreu_1734 had basal gene
      expression in glycerol absence; however, glycerol regulated its expression.
      Glycerol induced overexpression of cbiP and GldC genes (Strain ATCC 53608),
      probably to ensure its efficient utilization. On the contrary, glycerol
      concentration suppressed Lre_1734 expression in both analyzed strains, as a
      mechanism for 3-HPA accumulation. Down-regulation was observed in all the genes
      tested in strain ATCC 55730, probably due to feedback inhibition by 3-HPA.

PMID- 30240034
TI  - Human cerebral circuitry related to cardiac control: A neuroimaging meta
      analysis.
AB  - Serious arrhythmias often follow stroke, highlighting the important role that the
      cerebral cortex has in neural regulation of the heart. Neuroimaging studies
      reveal patterns of activation associated with autonomic cardiovascular responses.
      Using the activation likelihood estimation, a meta-analysis was performed to
      identify cortical activation patterns related to heart rate and heart rate
      variability across studies that used differing stimuli of cardiovascular arousal.
      Consistent associations with heart rate and heart rate variability were observed
      in the anterior cingulate, amygdala, insula, and prefrontal cortex, among others.
      Also, evidence is provided of insular lateralization associated with autonomic
      cardiac responses. Ann Neurol 2016;79:709-716.

PMID- 30240035
TI  - Length of myelin internodes of individual oligodendrocytes is controlled by
      microenvironment influenced by normal and input-deprived axonal activities in
      sensory deprived mouse models.
AB  - Oligodendrocytes myelinate neuronal axons to increase conduction velocity in the
      vertebrate central nervous system (CNS). Recent studies revealed that myelin
      formed on highly active axons is more stable compared to activity-silenced axons,
      and length of the myelin sheath is longer in active axons as well in the
      zebrafish larva. However, it is unclear whether oligodendrocytes preferentially
      myelinate active axons compared to sensory input-deprived axons in the adult
      mammalian CNS. It is also unknown if a single oligodendrocyte forms both longer
      myelin sheaths on active axons and shorter sheaths on input-deprived axons after
      long-term sensory deprivation. To address these questions, we applied
      simultaneous labeling of both neuronal axons and oligodendrocytes to mouse models
      of long-term monocular eyelid suturing and unilateral whisker removal. We found
      that individual oligodendrocytes evenly myelinated normal and input-deprived
      axons in the adult mouse CNS, and myelin sheath length on normal axons and input
      deprived axons formed by a single oligodendrocyte were comparable. Importantly,
      the average length of the myelin sheath formed by individual oligodendrocytes did
      change depending on relative abundance of normal against sensory-input deprived
      axons, indicating an abundance of deprived axons near an oligodendrocyte impacts
      on myelination program by a single oligodendrocyte.

PMID- 30240036
TI  - Cytonuclear incongruences hamper species delimitation in the socially polymorphic
      desert ants of the Cataglyphis albicans group in Israel.
AB  - Assessing whether behavioural, ecological or geographical factors trigger
      population divergence provides key insights into the biological processes driving
      speciation. Recent speciation in restricted geographic area without obvious
      ecological barriers prompts the question of the behavioural mechanisms underlying
      species divergence. In this context, we investigated phylogenetic relationships
      in the Cataglyphis albicans desert ant complex in Israel. We first determined
      accurate species delimitation using two mitochondrial and six nuclear genes, as
      well as 11 microsatellite markers to investigate cryptic species in this group,
      assessing reduction in gene flow between populations. We then investigated
      whether different species in this group exhibit distinct reproductive strategies,
      inferring social structure and queen-mating frequency in each species uncovered.
      Our findings highlight the presence of at least six distinct Cataglyphis albicans
      species in the restricted range of Israel; four of them co-occur in a 50 * 50 km
      area in North Negev, while two are endemic from there. However, our results
      reveal incongruences between nuclear and mitochondrial clustering, which
      complicate species identification and preclude the exclusive use of mtDNA to
      confidently delimit species in this group. Finally, we show that the different
      species of the C. albicans group in Israel exhibit quite similar reproductive
      strategies with most of them having colonies headed by a single queen mated with
      several males; colonies of one species were, however, headed by several queens.
      Overall, this weak variation across species thereby unlikely represents the main
      evolutionary force behind speciation of these sympatric species. We then discuss
      the potential evolutionary processes that underlie speciation in this group in
      the absence of clear geographical or ecological barriers.

PMID- 30240037
TI  - Retraction.
AB  - Calvo-Guirado JL, Aguilar-Salvatierra A, Ramirez-Fernandez MP, Mate Sanchez de
      Val JE, Delgado-Ruiz RA, Gomez-Moreno G. Bone response to collagenized xenografts
      of porcine origin (mp3(r)) and a bovine bone mineral grafting (4BONETM XBM)
      grafts in tibia defects: experimental study in rabbits. Clin Oral Impl Res.
      2016;27:1039-1046. The above article, published online on 5 October 2015 in Wiley
      Online Library (wileyonlinelibrary.com), and in Volume 27, pp. 1039-1046, has
      been retracted by agreement between the journal Editor in Chief, L Heitz
      Mayfield, and John Wiley & Sons Ltd. The retraction has been agreed due to image
      discrepancies, resulting in unreliable data. Images in Figures 3d, 4f, 6b, 6c,
      6e, and 6f have been used in other publications representing different time
      points and materials. Reference Calvo-Guirado JL, Aguilar-Salvatierra A, Ramirez
      Fernandez MP, Mate Sanchez de Val JE, Delgado-Ruiz RA. Gomez-Moreno G. Bone
      response to collagenized xenografts of porcine origin (mp3(r) ) and a bovine bone
      mineral grafting (4BONETM XBM) grafts in tibia defects: experimental study in
      rabbits. Clin Oral Impl Res., 2016;27: 1039-1046.
      https://doi.org/10.1111/clr.12681.

PMID- 30240038
TI  - PVC flooring at home and uptake of phthalates in pregnant women.
AB  - Phthalates are used as plasticizers in polyvinyl chloride (PVC) materials and it
      is known that phthalates may migrate into the surrounding environment and then
      become a source for human uptake. The aim of the study was to investigate whether
      residential PVC flooring was related to the urinary levels of phthalate
      metabolites determined in pregnant women. The data were from the Swedish SELMA
      study where sampling was conducted during the time period 2007-2010. Spot urine
      samples from 1674 women at the end of the first trimester were analyzed for 14
      metabolites from seven phthalates and one phthalate alternative. Data on flooring
      material in the kitchen and the parents' bedrooms as well as potential
      confounders were collected by postal questionnaires at the same time as the urine
      samples were taken. Multiple regression modeling by least square geometric mean
      and weighted quantile sum regression was applied to log-transformed and
      creatinine-adjusted phthalate metabolite concentrations adjusted for potential
      confounders from questionnaire data. This study has found significantly higher
      urinary levels of the BBzP metabolite (MBzP) in pregnant women living in homes
      with PVC flooring as compared to homes with other flooring materials.

PMID- 30240039
TI  - Emergency Department Procedural Sedation Practice Limitations: A Statewide
      California American College of Emergency Physicians Survey.
AB  - OBJECTIVES: We wanted to estimate the frequency and describe the nature of
      emergency department (ED) procedural sedation restrictions in the State of
      California. METHODS: We surveyed medical directors for all licensed EDs statewide
      regarding limitations on procedural sedation practice. Our primary outcome was
      the frequency of restrictions on procedural sedation, defined as an inability to
      administer moderate sedation, deep sedation, and typical ED sedative agents in
      accordance with American College of Emergency Physicians (ACEP) guidelines. Our
      secondary outcomes were the nature of these restrictions, who has imposed them,
      why they were imposed, and the perceived clinical impact. RESULTS: We obtained
      responses from 211 (64%) of the 328 EDs. Ninety-one (43%) reported conditional or
      total limitations on their ability to administer one or more of the following:
      moderate sedation, deep sedation, propofol, ketamine, or etomidate. Thirty-nine
      (18%) reported total restriction of at least one of these-most frequently a
      prohibition of deep sedation (18%). Local anesthesia directors were the most
      frequently cited creators and enforcers of these restrictions. Some respondents
      reported that, due to these restrictions, they used less effective sedatives,
      they performed procedures without sedation when sedation would have been
      preferred, and they observed inadequate sedation and pain control. CONCLUSIONS:
      In this statewide survey we found a substantial prevalence of practice
      limitations-mostly created by local anesthesia directors-that restrict the
      ability of emergency physicians to provide procedural sedation for their patients
      in accordance with ACEP guidelines. Deep sedation was prohibited in 18% of
      responding EDs. Our respondents describe adverse consequences to patient care.

PMID- 30240040
TI  - Successful treatment with dapsone for lupus profundus accompanied by xanthomatous
      reaction.

PMID- 30240041
TI  - Differentiation and quantification of the ochratoxin A producers Aspergillus
      ochraceus and Aspergillus westerdijkiae using PCR-DGGE.
AB  - Ochratoxin A (OTA) is a nephrotoxic, teratogenic, immunotoxic, and carcinogenic
      mycotoxin which is produced in tropical zones mainly by Aspergillus carbonarius,
      A. niger, A. ochraceus, and A. westerdijkiae. A. ochraceus and A. westerdijkiae
      species are phenotypically and genomically very close but A. westerdijkiae
      produce OTA at a very higher level than A. ochraceus. These species have been
      differentiated recently. The DNA primer pairs which were drawn so far are not
      specific and a genomic region of the same size is amplified for both species or
      they are too specific, and in this case, the DNA of a single species is
      amplified. To help preventing OTA contamination of foodstuffs, the PCR-DGGE
      (Denaturing Gradient Gel Electrophoresis) method was used to discriminate between
      A. ochraceus and A. westerdijkiae DNA fragments of the same size but with
      different sequences and thus faster access to a diagnosis of the toxigenic
      potential of the fungal microflora. The proposed methodology was able to
      differentiate A. westerdijkiae from A. ochraceus with only one primer pairs in a
      single run. A calibration based on initial DNA content was obtained from image
      analysis of the DGGE gels and a method of quantification of the two strains was
      proposed.

PMID- 30240042
TI  - Effects of physical exercise during pregnancy on maternal and infant outcomes in
      overweight and obese pregnant women: A meta-analysis.
AB  - BACKGROUND: Overweight and obesity are related to maternal and infant physical
      health, such as gestational diabetes, preeclampsia, and macrosomia. The purpose
      of this meta-analysis was to assess the effect of physical exercise on maternal
      and infant outcomes in overweight and obese pregnant women. METHODS: Two
      researchers independently searched Cochrane Library, Embase, PubMed, Web of
      Science, and ClinicalTrials.gov. for English-language articles based on
      randomized controlled trials examining physical exercise in overweight and obese
      pregnant women and its effect on maternal and infant outcomes. Primary outcomes
      were gestational weight gain and a relative risk of gestational diabetes.
      Secondary outcomes were gestational hypertension, preeclampsia, cesarean
      delivery, birthweight, large for gestational age, small for gestational age,
      macrosomia, and preterm birth. Risk bias was evaluated by Cochrane
      Collaboration's tool. The results of integration were reported as relative risks
      (RR), mean difference, or standard mean difference with 95% confidence intervals
      (CI). This meta-analysis was registered on PROSPERO on November 18, 2017, with
      registration number CRD42017081565. RESULTS: Thirteen studies involving 1439
      participants were included. Physical exercise reduced gestational weight gain
      (mean difference = -1.14 kg, 95% CI = [-1.67 to -0.62], P < 0.0001) and the risk
      of gestational diabetes (RR = 0.71, 95% CI = [0.57-0.89], P = 0.004) in
      overweight and obese pregnant women. There were no significant differences in
      other outcomes such as gestational hypertension, preeclampsia, cesarean delivery,
      birthweight, large for gestational age, small for gestational age, macrosomia,
      and preterm birth. CONCLUSIONS: Prenatal exercise interventions reduced
      gestational weight gain and the risk of gestational diabetes for overweight and
      obese pregnant women, which reinforced the benefits of exercise during pregnancy.
      However, no evidence was found with respect to benefits and/or harm for infants.
      Consideration should be taken when interpreting these findings as a result of the
      relative small sample size in this meta-analysis. Further larger well-designed
      randomized trials may be helpful to assess the short-term and long-term effects
      of prenatal exercise on maternal and infant outcomes.

PMID- 30240043
TI  - Retraction.
AB  - Retraction: Calvo-Guirado JL, Boquete-Cast ro A, Negri B, Delgado Ruiz R, Gomez
      Moreno G, Iezzi G. Crestal bone reactions to immediate implants placed at
      different levels in relation to crestal bone. A pilot study in Foxhound dogs.
      Clin Oral Impl Res. 2014; 25: 344-351. The above article, published online on 25
      January 2013 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 25,
      pp. 344-351, has been retracted by agreement between the journal Editor in Chief,
      L Heitz-Mayfield, and John Wiley & Sons Ltd. The retraction has been agreed due
      to numerical discrepancies in Tables 1-4, resulting in unreliable data. Reference
      Calvo-Guirado, J. L., Boquete-Cast ro, A., Negri, B., Delgado Ruiz, R.,Gomez
      Moreno, G., &Iezzi, G. (2014). Crestal bone reactions to immediate implants
      placed at different levels in relation to crestal bone. A pilot study in Foxhound
      dogs. Clinical Oral Implants Research, 25, 344-351.
      https://doi.org/10.1111/clr.12110.

PMID- 30240044
TI  - Distinct patterns of glia repair and remyelination in antibody-mediated
      demyelination models of multiple sclerosis and neuromyelitis optica.
AB  - Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory
      demyelinating disorders of the central nervous system with evidence of antibody
      mediated pathology. Using ex vivo organotypic mouse cerebellar slice cultures, we
      have demonstrated that recombinant antibodies (rAbs) cloned from cerebrospinal
      fluid plasmablasts of MS and NMO patients target myelin- and astrocyte-specific
      antigens to induce disease-specific oligodendrocyte loss and myelin degradation.
      In this study, we examined glial cell responses and myelin integrity during
      recovery from disease-specific antibody-mediated injury. Following exposure to MS
      rAb and human complement (HC) in cerebellar explants, myelinating
      oligodendrocytes repopulated the demyelinated tissue and formed new myelin
      sheaths along axons. Remyelination was accompanied by pronounced microglial
      activation. In contrast, following treatment with NMO rAb and HC, there was rapid
      regeneration of astrocytes and pre-myelinating oligodendrocytes but little
      formation of myelin sheaths on preserved axons. Deficient remyelination was
      associated with progressive axonal loss and the return of microglia to a resting
      state. Our results indicate that antibody-mediated demyelination in MS and NMO
      show distinct capacities for recovery associated with differential injury to
      adjacent axons and variable activation of microglia. Remyelination was rapid in
      MS rAb plus HC-induced demyelination. By contrast, oligodendrocyte maturation and
      remyelination failed following NMO rAb-mediated injury despite the rapid
      restoration of astrocytes and preservation of axons in early lesions.

PMID- 30240045
TI  - A postgraduate Optimum Birth module to increase midwives' readiness to work in
      midwifery-led settings: A mixed-methods evaluation.
AB  - BACKGROUND: Midwifery-led birth settings have been recommended as the most cost
      effective birthplaces for healthy women experiencing uncomplicated pregnancies.
      However, midwives complete most of their training in obstetric units where birth
      interventions are common. To prepare for working in a midwifery-led setting
      training is a key priority. This study evaluated a postgraduate-level midwifery
      module on Optimum Birth (defined as birth which supports physiology and
      empowerment, avoiding unnecessary intervention) designed to prepare midwives for
      supporting women in midwifery-led settings. METHODS: A mixed-methods design was
      employed. Pre-module and post-module questionnaires measured attitudes,
      knowledge, confidence, and learning outcomes. Qualitative data collection
      included a final-day focus group and 8- to 10-week follow-up interviews. The
      target for recruitment was 15 postgraduate midwives. Fifteen midwives practicing
      in three London boroughs enrolled of whom 14 completed the module. Pre-total and
      post-total scores were analyzed with paired-sample t tests. Qualitative data were
      analyzed using thematic analysis. RESULTS: Quantitative and qualitative data
      indicated that the module increased participants' self-reported skills,
      knowledge, and confidence in practicing Optimum Birth. Qualitative data indicated
      ways in which midwives were implementing changes to promote Optimum Birth in
      their place of work. Attitudes were highly positive pre-module and post-module.
      CONCLUSIONS: The Optimum Birth module provided appropriate training for preparing
      midwives for the shift toward working in midwifery-led settings. Midwifery
      leaders and managers should implement strategies to develop midwives' philosophy,
      knowledge, and skills to increase their readiness to work in midwifery-led birth
      settings.

PMID- 30240046
TI  - Trifluoromethanesulfinyl Chloride for Electrophilic Trifluoromethythiolation and
      Bifunctional Chlorotrifluoromethythiolation.
AB  - Trifluoromethanesulfinyl chloride (CF3 SOCl) has been introduced as a new reagent
      for C-H trifluoromethylthiolation of indoles, thiophenes, and ketones under
      catalyst-free conditions and in the absence of reductant. The disproportionation
      of CF3 SOCl to CF3 SO2 Cl and CF3 SCl provides two pathways for the
      trifluoromethylthiolation. Direct trifluoromethylthiolation with CF3 SCl or
      trifluoromethylsulfoxidation with CF3 SOCl is followed by reduction with CF3
      SOCl. This reagent can be used to functionalize benzothiophenes, benzofurans, and
      indenes under the promotion of Ag2 CO3 . It can also be used for
      trifluoromethylthiolation of thiols and benzeneselenols, and 1,2-bifunctional
      chlorotrifluoromethylthiolation of indoles, styrenes, and alkyenes. The method
      can also be extended for difluorometylthiolation reactions using CF2 HSOCl.

PMID- 30240047
TI  - Themed issue on child oral health.

PMID- 30240048
TI  - Rat enteric glial cells express novel isoforms of Interleukine-7 regulated during
      inflammation.
AB  - BACKGROUND: Neuroimmune interactions are essential to maintain gut homeostasis
      and prevent intestinal disorders but so far, the impact of enteric glial cells
      (EGC) on immune cells remains a relatively unexplored area of research. As a
      dysregulation of critical cytokines such as interleukine-7 (IL-7) was suggested
      to exacerbate gut chronic inflammation, we investigated whether EGC could be a
      source of IL-7 in the gastrointestinal tract. METHODS: Expression of IL-7 in the
      rat enteric nervous system was analyzed by immunochemistry and Q-PCR. IL-7
      variants were cloned and specific antibodies against rat IL-7 isoforms were
      raised to characterize their expression in the submucosal plexus. IL-7 isoforms
      were produced in vitro to analyze their impact on T-cell survival. KEY RESULTS:
      Neurons and glial cells of the rat enteric nervous system expressed IL-7 at both
      mRNA and protein levels. Novel rat IL-7 isoforms with distinct C-terminal parts
      were detected. Three of these isoforms were found in EGC or in both enteric
      neurons and EGC. Exposure of EGC to pro-inflammatory cytokines (IL-1beta and/or
      TNFalpha) induced an upregulation of all IL-7 isoforms. Interestingly, time
      course and intensity of the upregulation varied according to the presence or
      absence of exon 5a in IL-7 variants. Functional analysis on T lymphocytes
      revealed that only canonical IL-7 protects T cells from cell death. CONCLUSIONS
      AND INFERENCES: IL-7 and its variants are expressed by neurons and glial cells in
      the enteric nervous system. Their distinct expression and upregulation in
      inflammatory conditions suggest a role in gut homeostasis which could be critical
      in case of chronic inflammatory diseases.

PMID- 30240049
TI  - Global microbial metagenomics: An annotated selection of World Wide Web sites
      relevant to the topics in environmental microbiology.

PMID- 30240050
TI  - Retraction.
AB  - Ramirez-Fernandez MP, Calvo-Guirado JL, Arcesio Delgado-Ruiz R, Mate-Sanchez del
      Val JE, Gomez-Moreno G, Guardia J. Experimental model of bone response to
      xenografts of bovine origin (Endobon(r) ): a radiological and histomorphometric
      study. Clin Oral Impl Res. 2011;22: 727-734. The above article, published online
      on 29 December 2010 in Wiley Online Library (wileyonlinelibrary.com), and in
      Volume 22, pp. 727-734, has been retracted by agreement between the journal
      editor in chief, L Heitz-Mayfield, and John Wiley & Sons Ltd. The retraction has
      been agreed due to image discrepancies, resulting in unreliable data. Images in
      Figures 2b, 2c, 3a and 4a have been used in other publications representing
      different time points and experimental materials. Reference Ramirez-Fernandez MP,
      Calvo-Guirado JL, Arcesio Delgado-Ruiz R, Mate-Sanchez del Val JE, Gomez-Moreno
      G, Guardia J. Experimental model of bone response to xenografts of bovine origin
      (Endobon(r)): a radiological and histomorphometric study. Clin Oral Impl Res.
      2011;22: 727-734.https://doi.org/10.1111/j.1600-0501.2010.02052.x.

PMID- 30240052
TI  - Guidelines for development of Implant Dentistry in the next 10 years regarding
      innovation, education, certification, and associations.
AB  - BACKGROUND: During the third Summer Camp of European Association of
      Osseointegration (EAO), 40 junior representatives from various European societies
      and associations were brought together to discuss and explore the following
      topics in Implant Dentistry in the next 10 years: (I) certification, (II)
      societies and associations, (III) continuing education, and (IV) innovations.
      AIMS: The aims of all working groups were to identify and outline the present
      situation in the area of the selected topic and to propose improvements and
      innovations to be implemented in the following 10 years. MATERIALS AND METHODS:
      Four different groups were assigned randomly to one of the four working units.
      The method to discuss the selected topics was World Cafe. The summaries of four
      topics were then given to all participants for peer review. RESULTS AND
      CONCLUSIONS: All four groups presented the conclusions and guidelines
      accordingly: (I) The recognition for Implant Dentistry and accreditation of
      training programs would lead to an improvement of the quality of care to the
      benefit of the patients; (II) Dental associations and societies have to
      continuously improve communication to meet needs of dental students,
      professionals, and patients (III) European Dental Board should be installed and
      become responsible for continue dental education; (IV) dental engineering, peri
      implant diseases, and digital workflow in dentistry currently have limited tools
      that do not guarantee predictable results.

PMID- 30240051
TI  - Injectable, compression-resistant polymer/ceramic composite bone grafts promote
      lateral ridge augmentation without protective mesh in a canine model.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that a
      compression-resistant bone graft augmented with recombinant human morphogenetic
      protein-2 (rhBMP-2) will promote lateral ridge augmentation without the use of
      protective mesh in a canine model. MATERIALS & METHODS: Compression-resistant
      (CR) bone grafts were evaluated in a canine model of lateral ridge augmentation.
      Bilateral, right trapezoidal prism-shaped defects (13-14 mm long * 8-9 mm wide *
      3-4 mm deep at the base) in 13 hounds (two defects per hound) were treated with
      one of four groups: (i) absorbable collagen sponge + 400 MUg rhBMP-2/ml (ACS,
      clinical control) protected by titanium mesh, (ii) CR without rhBMP-2 (CR,
      negative control), (iii) CR + 200 MUg rhBMP-2 (CR-L), or (iv) CR + 400 MUg rhBMP
      2 (CR-H). All animals were euthanized after 16 weeks. Ridge height and width and
      new bone formation were assessed by MUCT, histology, and histomorphometry. The
      release kinetics of rhBMP-2 from CR bone grafts in vitro and in vivo in a femoral
      condyle defect model in rabbits was also evaluated. RESULTS: All four bone grafts
      promoted new bone formation (11-31.6 volume%) in the lateral ridge defects. For
      CR grafts, ridge height and width increased in a dose-responsive manner with
      increasing rhBMP-2 concentration. Ridge height and width measured for CR-H
      without the use of protective mesh was comparable to that measured for ACS with a
      protective mesh. CONCLUSIONS: At the same dose of rhBMP-2, an injectable,
      compression-resistant bone graft resulted in a comparable volume of new bone
      formation with the clinical control (ACS). These findings highlight the potential
      of compression-resistant bone grafts without the use of protective mesh for
      lateral ridge augmentation.

PMID- 30240053
TI  - Retraction.
AB  - Calvo-Guirado JL, Ramirez-Fernandez MP, Mate-Sanchez JE, Bruno N, Velasquez P, de
      Aza PN. Enhanced bone regeneration with a novel synthetic bone substitute in
      combination with a new natural cross-linked collagen membrane: radiographic and
      histomorphometric study. Clin Oral Impl Res. 2015;26: 454-464. The above article
      published online on 10 April 2014 in Wiley Online Library
      (wileyonlinelibrary.com), and in Volume 26, pp. 454-464 has been retracted by
      agreement between the journal Editor in Chief, L Heitz-Mayfield and John Wiley &
      Sons Ltd. The retraction has been agreed due to image discrepancies, resulting in
      unreliable data. Images in Figures 5, 6b, 7b and 7c have been used in other
      publications representing different materials, experiments, experimental
      conditions and time points. Reference Calvo-Guirado JL, Ramirez-Fernandez MP,
      Mate-Sanchez JE, Bruno N, Velasquez P, de Aza PN. Enhanced bone regeneration with
      a novel synthetic bone substitute in combination with a new natural cross-linked
      collagen membrane: radiographic and histomorphometric study. Clin Oral Impl Res.
      2015;26: 454-464. https://doi.org/10.1111/clr.12399.

PMID- 30240054
TI  - Retraction.
AB  - Calvo-Guirado JL, Delgado-Ruiz RA, Ramirez-Fernandez MP, Mate-Sanchez JE, Ortiz
      Ruiz A, Marcus A. Histomorphometric and mineral degradation study of Ossceram(r)
      : a novel biphasic B-tricalcium phosphate, in critical size defects in rabbits.
      Clin Oral Impl Res. 2012;23: 667-675. The above article, published online on 15
      April 2011 in Wiley Online Library (wileyonlinelibrary.com), and in Volume 23,
      pp. 667-675, has been retracted by agreement between the journal Editor in Chief,
      L Heitz-Mayfield, and John Wiley & Sons Ltd. The retraction has been agreed due
      to image discrepancies, resulting in unreliable data. It has not been possible to
      prove the validity of the images. Images in Figures 11c, 11f, 12c and 12f have
      been used in other publications representing different time points and materials.
      Images in Figures 5a, 5e and Figures 5b, 5d represent image manipulation labeled
      as different time points. Reference Calvo-Guirado JL, Delgado-Ruiz RA, Ramirez
      Fernandez MP, Mate-Sanchez JE, Ortiz-Ruiz A, Marcus A. Histomorphometric and
      mineral degradation study of Ossceram(r) : a novel biphasic B-tricalcium
      phosphate, in critical size defects in rabbits. Clin Oral Impl Res. 2012;23: 667
      675. https://doi.org/10.1111/j.1600-0501.2011.02193.x.

PMID- 30240055
TI  - Retraction.
AB  - Calvo-Guirado JL, Ramirez-Fernandez MP, Delgado-Ruiz RA, Mate-Sanchez JE,
      Velasquez P, de Aza PN. Influence of Biphasic beta-TCP with and without the use
      of collagen membranes on bone healing of surgically critical size defects. A
      radiological, histological, and histomorphometric study. Clin Oral Impl Res.
      2014;25: 1228-1238. The above article, published online on 12 September 2013 in
      Wiley Online Library (wileyonlinelibrary.com), and in Volume 25, pp. 1228-1238,
      has been retracted by agreement between the journal Editor in Chief, L Heitz
      Mayfield, and John Wiley & Sons Ltd. The retraction has been agreed due to image
      discrepancies, resulting in unreliable data. It has not been possible to prove
      the validity of the images. Images in Figure 10 have been used in other
      publications representing different time points and experimental conditions.
      Reference Calvo-Guirado JL, Ramirez-Fernandez MP, Delgado-Ruiz RA, Mate-Sanchez
      JE, Velasquez P, de Aza PN. Influence of Biphasic beta-TCP with and without the
      use of collagen membranes on bone healing of surgically critical size defects. A
      radiological, histological, and histomorphometric study. Clin Oral Impl Res.
      2014;25: 1228-1238. https://doi.org/10.1111/clr.12258.

PMID- 30240056
TI  - Retraction.
AB  - Negri B, Calvo-Guirado JL, Pardo-Zamora G, Ramirez-Fernandez MP, Delgado-Ruiz RA,
      Munoz-Guzon F. Peri-implant bone reactions to immediate implants placed at
      different levels in relation to crestal bone. Part I: a pilot study in dogs. Clin
      Oral Impl Res. 2012;23: 228-235. The above article, published online on 24 March
      2011 in Wiley Online Library (wileyonlinelibrary.com) and in Volume 23, pp. 228
      235, has been retracted by agreement between the journal Editor in Chief, L Heitz
      Mayfield, and John Wiley & Sons Ltd. The retraction has been agreed due to image
      discrepancies, resulting in unreliable data. Images in Figure 6a have been used
      in another publication representing different time points. Reference Negri B,
      Calvo-Guirado JL, Pardo-Zamora G, Ramirez-Fernandez MP, Delgado-Ruiz RA, Munoz
      Guzon F. Peri-implant bone reactions to immediate implants placed at different
      levels in relation to crestal bone. Part I: a pilot study in dogs. Clin Oral Impl
      Res. 2012;23: 228-235. https://doi.org/10.1111/j.1600-0501.2011.02158.x.

PMID- 30240057
TI  - Retraction.
AB  - Negri B, Calvo-Guirado JL, Ramirez-Fernandez MP, Mate Sanchez-de Val J, Guardia
      J, Munoz-Guzon F. Peri-implant bone reactions to immediate implants placed at
      different levels in relation to crestal bone. Part II: a pilot study in dogs.
      Clin Oral Impl Res. 2012;23: 236-244. The above article, published online on 5
      September 2011 in Wiley Online Library (wileyonlinelibrary.com) and in Volume 23,
      pp. 236-244, has been retracted by agreement between the journal Editor in Chief,
      L Heitz-Mayfield, and John Wiley & Sons Ltd. The retraction has been agreed due
      to image discrepancies, resulting in unreliable data. Images in Figure 8 have
      been used in another publication representing different time points. Reference
      Negri B, Calvo-Guirado JL, Ramirez-Fernandez MP, Mate Sanchez-de Val J, Guardia
      J, Munoz-Guzon F. Peri-implant bone reactions to immediate implants placed at
      different levels in relation to crestal bone. Part II: a pilot study in dogs.
      Clin Oral Impl Res. 2012;23: 236-244. https://doi.org/10.1111/j.1600
      0501.2011.02290.x.

PMID- 30240058
TI  - Retraction.
AB  - Ramirez-Fernandez M, Calvo-Guirado JL, Delgado-Ruiz RA, Mate-Sanchez del Val JE,
      Vicente-Ortega V, Meseguer-Olmos L. Bone response to hydroxyapatites with open
      porosity of animal origin (porcine [OsteoBiol(r) mp3] and bovine [Endobon(r) ]):
      a radiological and histomorphometric study. Clin Oral Impl Res. 2011;22: 767-773.
      The above article, published online on 18 January 2011 in Wiley Online Library
      (wileyonlinelibrary.com), and in Volume 22, pp. 767-773, has been retracted by
      agreement between the journal Editor in Chief, L Heitz-Mayfield, and John Wiley &
      Sons Ltd. The retraction has been agreed due to image discrepancies, resulting in
      unreliable data. Images in Figure 2f, 3f, 3g and 4g have been used in other
      publications representing different time points. Images in Figure 1c, 2c, 1f and
      2f represent different time points within the same publication. Reference Ramirez
      Fernandez M, Calvo-Guirado JL, Delgado-Ruiz RA, Mate-Sanchez del Val JE, Vicente
      Ortega V, Meseguer-Olmos L. Bone response to hydroxyapatites with open porosity
      of animal origin (porcine [OsteoBiol(r) mp3] and bovine [Endobon(r) ]): a
      radiological and histomorphometric study. Clin Oral Impl Res. 2011;22: 767-773.
      https://doi.org/10.1111/j.1600-0501.2010.02058.x.

PMID- 30240059
TI  - Prospective comparison of a fast 1.5-T biparametric with the 3.0-T
      multiparametric ESUR magnetic resonance imaging protocol as a triage test for men
      at risk of prostate cancer.
AB  - OBJECTIVE: To compare prospectively the diagnostic performance of a biparametric
      (T2-weighted imaging [T2WI] and diffusion-weighted imaging [DWI]) 1.5-T fast
      magnetic resonance imaging (fMRI) protocol with the standard 3.0-T
      multiparametric MRI (mpMRI) protocol of the European Society of Urological
      Imaging (ESUR) in men referred for a prostate biopsy. PATIENTS AND METHODS:
      Ninety patients with a prostate cancer (PCa) risk of >=10% according to the SWOP
      calculator 4 underwent first fMRI and then the reference mpMRI. Patients with
      Prostate Imaging Reporting and Data System (PI-RADS) v.2 lesions >=3/5 on the
      mpMRI were scheduled for MRI/ultrasonography (US) fusion-guided prostate biopsy.
      Performance of fMRI was assessed using receiver-operating characteristic curve
      analysis and mpMRI as reference. Calculation of inter-technique agreement on PI
      RADS v.2 score by Cohen's kappa. RESULTS: The diagnostic accuracy of fMRI shown
      by the lesion-based analysis was excellent: area under the curve (AUC) 0.961 (P <
      0.001), sensitivity 95%, specificity 97%, positive predictive value (PPV) 99%,
      negative predictive value (NPV) 89%. The patient-based analysis showed an AUC for
      fMRI of 0.975 (P < 0.001), a sensitivity of 98%, a specificity of 97%, a PPV of
      98% and an NPV of 97%. Agreement on the PI-RADS score between both protocols was
      found to be good (kappa = 0.78 [0.57; 0.99]); fMRI missing PI-RADS 4 lesions in
      three patients. Biopsy results showed no cancer in two patients (two cores per
      nodule) and Gleason 6 cancer in one patient. There was only one false-positive
      fMRI, with a PI-RADS score of 4, whose biopsy was negative. CONCLUSION: In the
      triage of men with a high risk of PCa for prostate biopsy, an f MRI protocol (1.5
      T magnet, T2WI + DWI, <15 min) may safely replace the traditional ESUR 3.0-T
      mpMRI protocol, saving time and contrast injection.

PMID- 30240060
TI  - Astrocytes, the rising stars of the glioblastoma microenvironment.
AB  - Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths
      worldwide every year. The mean survival of patients with GBM remains below 20
      months despite current available therapies. GBM cells' interactions with their
      stromal counterparts are crucial for tumor development. Astrocytes are glial
      cells that comprise ~50% of all brain cells and are therefore likely to establish
      direct contact with GBM cells. As other tumor cell types can hijack fibroblasts
      or immune cells to facilitate tumor growth, GBM cells can actually activate
      astrocytes, namely, the tumor associated astrocytes (TAAs), to promote GBM
      invasion in the healthy tissue. TAAs have thus been shown to be involved in GBM
      cells growth and limited response to radiation or chemotherapy (i.e.,
      Temozolomide). Nevertheless, even though the interest in the cancer research
      community is increasing, the role of TAAs during GBM development is still
      overlooked. Yet, obtaining an in-depth understanding of the mechanisms by which
      TAAs influence GBM progression might lead to the development of new therapeutic
      strategies. This article therefore reports the different levels of GBM
      progression at which TAAs have been recently described to be involved in,
      including tumor cells' proliferation/invasion and resistance to therapies,
      especially through the activity of extracellular vesicles.

PMID- 30240061
TI  - The "Wiser" oncoplastic reduction mammaplasty - An approach to challenging medial
      defects.
AB  - Medial defects created by breast-conservation surgery pose a significant
      challenge to oncoplastic reduction mammaplasty, especially with superficial
      tumors that necessitate resection of overlying skin. These tumors lie outside of
      the standard breast reduction excision pattern, and require modifications to the
      routine Wise approach. We present one modification - the "Wiser" oncoplastic
      reduction mammaplasty technique - that utilizes spared tissue along the lower
      pole, and a medial dermoglandular pedicle to address both skin and parenchymal
      defects created by the tumor resection.

PMID- 30240062
TI  - Human Femoral Vein Diameter and Topography of Valves and Tributaries: A Post
      Mortem Analysis.
AB  - The femoral vein (FV) is a clinically important vessel. Failure of its valves can
      lead to chronic venous insufficiency (CVI) with severe manifestations such as
      painful ulcers. Although they are crucial for identifying suitable implant sites
      for therapeutic valves, studies on the topography of FV tributaries and valves
      are rare. Moreover, the femoral vein diameter (FVD) must be known to assess the
      morphometric requirements for valve implants. To reassess the anatomical
      requirements for valve implants, 155 FVs from 82 human corpses were examined.
      FVDs and tributary and valve topographies were assessed using a laboratory
      straightedge. The FVD increased from 6 mm in the distal femoropopliteal vein to
      11 mm in the iliofemoral vein proximal to the saphenofemoral junction (SFJ).
      Diameters were significantly bigger in males than females. Height correlated
      positively with FVD. Distal to the SFJ, within a distance of 38 cm, one to eight
      valves were present. Up to two valves were present within 10 cm proximal to the
      SFJ. Individual tributary and valve topography must be considered to ensure
      appropriate design and successful implantation of a venous valve for CVI therapy
      in the FV. A suitable implant site would be proximal to the SFJ via an
      infrainguinal transfemoral access. Clin. Anat. 31:1065-1076, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30240063
TI  - Intra- and inter-examiner agreement when assessing radiographic implant bone
      levels: Differences related to brightness, accuracy, participant demographics and
      implant characteristics.
AB  - OBJECTIVES: Evaluate intra- and inter-examiner agreement of radiographic marginal
      bone level (MBL) assessment around Branemark single implants; and whether
      agreement related to radiograph brightness, discrimination level (accuracy),
      participant demographics or implant characteristics. MATERIALS AND METHODS:
      Seventy-four participants assessed MBLs of 100 digital radiographs twice with
      normal brightness, and twice with increased brightness. Intra-examiner agreement
      with and without increased brightness to the same thread, and within one thread;
      and inter-examiner agreement as compared with the group (defined by the mode) for
      the first assessments with and without increased brightness, to the same thread,
      and within one thread were calculated with Cohen's Kappa. Relationships between
      agreement, thread discrimination level (accuracy), brightness, participant and
      implant characteristics were explored. RESULTS: When assessing 100 "Normal"
      radiographs twice, a participant on average assessed 24% differently to
      themselves (poor intra-examiner agreement, median Kappa 0.58, range 0.21-0.82);
      and 28% differently to other participants (poor inter-examiner agreement, median
      Kappa 0.53, range 0.05-0.80). Agreement within examiners improved when
      radiographs were "Bright" (median Kappa 0.58 vs. 0.62, p < 0.001, accuracy to
      same thread; median Kappa 0.94 vs. 0.96, p < 0.001, accuracy within one thread).
      Agreement between examiners was neither better nor worse when radiographs were
      "Bright" (median Kappa 0.53 vs. 0.55, p = 0.64, accuracy to same thread; median
      Kappa 0.93 vs. 0.93, p = 0.23, accuracy within one thread). Intra- and inter
      examiner agreements were lower when accuracy to the same thread was required (p <
      0.001, p < 0.001). Neither intra- nor inter-examiner agreement related to age,
      time since graduation, specialty, viewing device, implant experience, external
      hex familiarity, periimplantitis treatment experience, implant location or width
      (p-values 0.05-0.999). Intra-examiner agreement increased across dental
      assistants (n = 11), general dentists (n = 16) and specialists (n = 47) ("Bright"
      assessments, p = 0.045, median Kappa's 0.55, 0.60, 0.65 respectively); and for
      females (n = 8, males = 58) ("Normal" assessments, p = 0.019, median 0.68 vs.
      0.55), but female numbers were low. CONCLUSIONS: Agreement within and between
      examiners when assessing MBLs was poor. Disagreement occurred around 25% of the
      time, potentially affecting consistent disease assessments. No participant or
      implant characteristic clearly affected agreement. Brighter radiographs improved
      intra-examiner agreement. Overall, perceived MBL changes below 1 mm are likely
      due to human, not biological variation.

PMID- 30240064
TI  - Breast MRI findings of fibroadenoma with hemorrhagic infarction.

PMID- 30240065
TI  - Retraction.
AB  - Calvo-Guirado J-L, Gomez-Moreno G, Mate-Sanchez J-E, Lopez-Mari L, Delgado-Ruiz
      R, Romanos GE. New bone formation in bone defects after melatonin and porcine
      bone grafts: experimental study in rabbits. Clin Oral Impl Res. 2015;26: 399-406.
      The above article, published online on 6 March 2014 in Wiley Online Library
      (wileyonlinelibrary.com), and in Volume 26, pp. 399-406, has been retracted by
      agreement between the journal Editor-in-chief, L Heitz-Mayfield, and John Wiley &
      Sons Ltd. The retraction has been agreed due to image discrepancies, resulting in
      unreliable data. Images in Figures 3a and 9 have been used in other publications
      representing different time points. Reference Calvo-Guirado J-L, Gomez-Moreno G,
      Mate-Sanchez J-E, Lopez-Mari, L, Delgado-Ruiz R, Romanos GE. New bone formation
      in bone defects after melatonin and porcine bone grafts: experimental study in
      rabbits. Clin Oral Impl Res,. 2015;26: 399-406.
      https://doi.org/10.1111/clr.12364.

PMID- 30240066
TI  - Thermally Activated Delayed Fluorescent Polymers: Structures, Properties, and
      Applications in OLED Devices.
AB  - Thermally activated delayed fluorescent (TADF) polymers are promising emitting
      materials to realize highly efficient, large-scale, and low-cost organic light
      emitting diodes (OLEDs) since they exhibit various advantages such as heavy-metal
      free structures, 100% theoretical internal quantum efficiency, and ease of large
      area fabrication through solution process. At present, TADF polymers are still
      limited in category and complicated in preparation, which hinders their
      proceeding into industrial application. Besides, a still-too-low quantum
      efficiency poses a challenge for TADF-polymer-based OLEDs. In this review,
      different topologies and design strategies of the existing TADF polymers are
      covered, their structure-property relationships are illustrated, their first
      applications in OLED devices are discussed, and finally, an outlook of promising
      design rules for future TADF polymers is provided. The hope is to inspire
      researchers to develop TADF polymers prepared by easier synthesis strategies and
      higher external quantum efficiency to promote emitter application.

PMID- 30240067
TI  - Quantitative Binding Behavior of Intrinsically Disordered Proteins to
      Nanoparticle Surfaces at Individual Residue Level.
AB  - The quantitative and predictive understanding how intrinsically disordered
      proteins (IDPs) interact with engineered nanoparticles has potentially important
      implications for new therapeutics as well as nanotoxicology. Based on a recently
      developed solution 15 N NMR relaxation approach, the interactions between four
      representative IDPs with silica nanoparticles are reported at atomic detail. Each
      IDP possesses distinct binding modes, which can be quantitatively explained by
      the local amino-acid residue composition using a "free residue interaction
      model". The model was parameterized using the binding affinities of free
      proteinogenic amino acids along with long-range effects, derived by site-specific
      mutagenesis, that exponentially scale with distance along the primary sequence.
      The model, which is accessible through a web server, can be applied to predict
      the residue-specific binding affinities of a large number of IDPs.

PMID- 30240068
TI  - Paraneoplastic neurologic syndrome as a presentation of underlying breast
      malignancy.
AB  - While breast cancer most commonly presents as a screen-detected mammographic
      finding or a breast symptom, in very rare instances it may first present as a
      paraneoplastic neurologic syndrome (PNS; Surg Case Rep, 2015;1:59; Ann Neurol
      2004;56:715). Fewer than 1% of breast cancer patients have PNS, and an even
      smaller percentage initially present with neurologic symptoms (J Neurol Neurosurg
      Psychiatry, 2004;75:ii43). We report a case series of three patients who
      presented with neurological disorders suspicious for PNS, and were subsequently
      found to have underlying breast cancer. We follow this with a discussion of key
      clinical features of management considerations in paraneoplastic syndromes
      secondary to breast malignancy.

PMID- 30240069
TI  - A rare case of pleomorphic adenoma of the breast: Ultrasonography and pathology
      findings.

PMID- 30240070
TI  - Antifungal Activities of Isoflavonoids from Uromyces striatus Infected Alfalfa.
AB  - Fungal pathogens constitute a severe yield-limiting factor for the pasture crop
      alfalfa (Medicago sativa L.). Eleven phenolic compounds, including a new
      isoflavane, were isolated from the Uromyces striatus Schroet. infected alfalfa.
      The effect of infection with U. striatus Schroet. on the phytochemical profile of
      alfalfa was investigated using ultra-performance liquid chromatography (UPLC),
      and the antifungal properties of isolated compounds against a range of pathogens
      were tested. It was found that the contents of most of the isolated compounds in
      U. striatus infected alfalfa were higher than those in healthy alfalfa. Compounds
      1-5 exhibited a moderate inhibitory activity against Curvularia lunata with
      40.14+/-1.63 %, 48.03+/-1.22 %, 57.54+/-1.18 %, 50.10+/-1.56 %, and 61.54+/-2.14
      % inhibition ratio at the concentration of 50 MUg/mL. Compounds 3 and 5 showed a
      weak inhibitory activity against Fusarium graminearum with the EC50 values of
      104.2+/-2.66 and 123.0+/-1.23 MUg/mL, and a moderate inhibitory activity against
      Bipolaris sorokinianum with the EC50 values of 39.1+/-2.05 and 95.0+/-1.01
      MUg/mL, respectively. In pot experiments with wheat, compounds 1-5 possessed
      desirable protective efficacy of over 80 % and curative effectiveness of over 50
      % against Puccinia striiformis f. sp. tritici at a concentration of 0.5 mg/mL.

PMID- 30240071
TI  - Tough, Stimuli-Responsive, and Biocompatible Hydrogels with Very High Water
      Content.
AB  - Some marine creatures like jellyfish have gel-like bodies consisting mostly of
      water (above 95 wt%). Yet, their gel-like bodies still show quite good mechanical
      properties and can respond to external stimuli. Artificial hydrogels with very
      high water content are generally extremely weak, and hence their practical
      applications are strongly limited. Inspired by jellyfish, tough and biocompatible
      poly(vinyl alcohol)/sodium polyacrylate (PVA/PAANa) hydrogels with very high
      equilibrium water content (98.23-99.58 wt%) are developed. The equilibrium
      swollen PVA/PAANa hydrogels show good mechanical properties, with elastic
      modulus, tensile strength, and elongation up to 0.046 MPa, 0.14 MPa, and 206%,
      respectively, very close to those of jellyfish mesoglea. Moreover, the PVA/PAANa
      hydrogels can respond to external multi-stimuli distinctly, such as metal
      cations, pH, and salts. Very impressively, the PVA/PAANa hydrogel can easily
      distinguish tap water from deionized water, and its detection limit of metal
      cations can be as low as 10-4  mol L-1 . Cell cytotoxicity tests and in vivo
      biocompatibility tests prove that the PVA/PAANa hydrogels have excellent
      biocompatibility. The tough, stimuli-responsive, and biocompatible hydrogels with
      very high water content may find a variety of practical applications in load
      bearing biomaterials, detection, sensors, and agricultural fields.

PMID- 30240073
TI  - New insights into the astonishing diversity of hormone functions.

PMID- 30240072
TI  - Use of existing electronic health care databases to evaluate medication safety in
      pregnancy: Triptan exposure in pregnancy as a case study.
AB  - PURPOSE: The recent expansion of electronic health and medical record systems may
      present an opportunity to generate robust post-approval safety data and obviate
      the limitations of prospective pregnancy exposure registries. We examined and
      compared, over the same time frame, the outcomes of triptan exposure in pregnancy
      using (1) a retrospective claims database and (2) a previously completed
      pregnancy registry. METHODS: Using the Marketscan database, the risk of major
      birth defects was ascertained in live-born infants whose birth mothers were
      exposed to sumatriptan, naratriptan, or sumatriptan/naproxen during pregnancy.
      The frequencies of outcomes observed were compared with the findings of the 16
      year sumatriptan, naratripan, and sumatriptan/naproxen prospective pregnancy
      registry. RESULTS: About 5120 pregnancies were identified in the retrospective
      claims cohort in contrast to 617 included in the prospective registry during the
      same time frame. The proportion of major birth defects among first-semester
      sumatriptan exposures was 4.0%, which is exactly the same as the proportion of
      major birth defects reported for first-semester sumatriptan exposures in the
      registry. There were very few non-livebirth outcomes in both the claims analyses
      and registry. CONCLUSIONS: These results confirm broad agreement between the
      database analysis and the registry regarding the safety of triptans during
      pregnancy. Of note, the number of triptan-exposed pregnancies identified in this
      large US database was about 7-fold that included in the prospective registry over
      the same time frame. The findings of this study support an approach of using
      existing health care database (s) in the post-approval assessment of medication
      exposure in pregnancy.

PMID- 30240075
TI  - The ACEM Primary Examination is still relevant: No.

PMID- 30240074
TI  - S???Sn Tetrel Bonds in the Activation of Peroxisome Proliferator-Activated
      Receptors (PPARs) by Organotin Molecules.
AB  - In this study, a PDB (Protein Data Bank) analysis and theoretical calculations
      (PBE0-D3/def2-TZVP level of theory) were combined to analyze the impact of S???Sn
      tetrel-bonding interactions in the activation mechanism of peroxisome
      proliferator-activated receptors (PPARs) by two organotin derivatives,
      triphenyltin (TPT) and tributyltin (TBT). The presence of a covalently bonded
      CYS285 to the organotin molecule was found to be key to enhance the sigma-hole
      donor ability of the tin atom, thus strengthening the tetrel-bonding interaction
      with a sulfur atom belonging to a vicinal methionine residue (MET364).

PMID- 30240076
TI  - The Primary Examination: A tale of two countries.

PMID- 30240078
TI  - In this October issue.

PMID- 30240079
TI  - A clinicopathologic study of invasive apocrine carcinoma of the breast: A single
      center experience.

PMID- 30240080
TI  - Robotic nipple-sparing mastectomy: The first experience from Indian subcontinent.

PMID- 30240081
TI  - Use of nutritional devices in Cornelia de Lange syndrome: Data from a large
      Italian cohort.
AB  - Cornelia de Lange syndrome (CdLS) is a genetic condition characterized by
      intellectual disability, peculiar facial dysmorphisms, multiorgan malformations,
      and growth problems. Majority cases of CdLS are caused by mutations in genes of
      Cohesin pathway. Although feeding problems are a well-known feature, no specific
      data have been published about the use of nutritional devices. We analyzed use,
      type, time of introduction, and duration of nutritional devices in 73 CdLS
      patients. In total, 29/73 (40%) used a device; nasogastric tube (NGT) in 28/73
      (38%) and percutaneous endoscopic gastrostomy (PEG) in 7/73 (10%). NGT was placed
      during the first days/weeks of life. 19/28 (68%) maintained it for less than 3
      months, 7/28 (25%) for a period between 3 and 12 months, while 2/28 (7%) for more
      than 1 year. PEG was placed within the first year in 4/7 (57%) and removed in two
      patients after 4 years These data have been matched with a wide number of genetic
      and clinical variables. Presence of upper limb malformations is positively
      correlated with the need of a device. From the opposite side, the use of a device
      positively correlates with a more severe prognosis as regard growth, intellectual
      development and disease severity. Our data show that nutritional devices are
      frequently used by CdLS patients, also if the majority of them (93.1%) succeed
      with time in achieving a normal oral nutrition. Finally, the need, the type of
      device used and the duration of NGT or/plus PEG can be considered a further sign
      of worse prognosis of the disease itself.

PMID- 30240082
TI  - Erratum.

PMID- 30240083
TI  - Severe and fatal childhood poisoning in the United Kingdom.

PMID- 30240084
TI  - Left post-auricular swelling in a child.

PMID- 30240085
TI  - Left post-auricular swelling in a child.

PMID- 30240086
TI  - Irreversible laser-induced maculopathy in a child.

PMID- 30240087
TI  - Burdens of home ventilation of children.

PMID- 30240088
TI  - Adolescent body-mass index and cardiovascular death.

PMID- 30240089
TI  - Joseph's problem.

PMID- 30240090
TI  - Toddler with a tarnished tongue.

PMID- 30240091
TI  - Toddler with a tarnished tongue.

PMID- 30240092
TI  - Sibling rivalry.

PMID- 30240093
TI  - Female genital mutilation.

PMID- 30240094
TI  - Impact of insurance coverage and socioeconomic factors on screening mammography
      patients' selection of digital breast tomosynthesis versus full-field digital
      mammography.

PMID- 30240095
TI  - The effect of weight on labor market outcomes: An application of genetic
      instrumental variables.
AB  - This paper contributes to the literature on the labor market consequences of
      obesity by using a novel instrument: genetic risk score, which reflects the
      predisposition to higher body mass index (BMI) across many genetic loci. We
      estimate instrumental variable models of the effect of BMI on labor market
      outcomes using Finnish data that have many strengths, for example, BMI that is
      measured rather than self-reported, and data on earnings and social income
      transfers that are from administrative tax records and are thus free of the
      problems associated with nonresponse, reporting error or top coding. The
      empirical results are sensitive to whether we use a narrower or broader genetic
      risk score, and to model specification. For example, models using the narrower
      genetic risk score as an instrument imply that a one-unit increase in BMI is
      associated with 6.9% lower wages, 1.8% fewer years employed, and a 3 percentage
      point higher probability of receiving any social income transfers. However, when
      we use a newer, broader genetic risk score, we cannot reject the null hypothesis
      of no effect. Future research using genetic risk scores should examine the
      sensitivity of their results to the risk score used.

PMID- 30240096
TI  - Correlation between Apolipoprotein E genotype and brain metabolism in amyotrophic
      lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to evaluate the metabolic
      correlates of Apolipoprotein E (APOE) genotype in amyotrophic lateral sclerosis
      (ALS) and to investigate the role of epsilon2 as a risk factor for cognitive
      impairment. METHODS: A total of 159 ALS cases underwent APOE and ALS-related
      genes analysis, neuropsychological assessment and cerebral 18 F-2-fluoro-2-deoxy
      D-glucose positron emission tomography. The APOE genotype was regressed against
      whole brain metabolism as assessed by 18 F-2-fluoro-2-deoxy-D-glucose positron
      emission tomography, with age, sex, education, type of onset and C9orf72 status
      as covariates. RESULTS: Brain metabolism was significantly positively correlated
      with APOE genotype from epsilon2/epsilon2 to epsilon3/epsilon4 in the left
      prefrontal [Brodmann area (BA) 10], orbitofrontal (BAs 11, 45, 47) and anterior
      cingulate (BA 32) cortices. There was a tendency to a relative hypometabolism
      going towards the epsilon2/epsilon2 extreme. CONCLUSIONS: We found a highly
      significant, relatively lower metabolism in association with the epsilon2 allele
      in extra-motor areas typically affected in frontotemporal dementia (left
      prefrontal, orbitofrontal and anterior cingulate cortices), strengthening the
      finding of a role of epsilon2 as a risk factor for cognitive impairment in ALS.
      Our data suggested a link between cholesterol homeostasis and neurodegeneration.

PMID- 30240097
TI  - Effect of oral isotretinoin on the nucleo-cytoplasmic distribution of FoxO1 and
      FoxO3 proteins in sebaceous glands of patients with acne vulgaris.
AB  - Oral isotretinoin is the most effective anti-acne drug with the strongest sebum
      suppressive effect caused by sebocyte apoptosis. It has been hypothesized that
      upregulation of nuclear FoxO transcription factors and p53 mediate isotretinoin
      induced sebocyte apoptosis in vivo. It is the aim of our study to analyse the
      distribution of the pro-apoptotic transcription factors FoxO1 and FoxO3 in the
      nuclear and cytoplasmic compartments of human sebocytes in vivo before and during
      isotretinoin treatment of acne patients. Immunohistochemical analysis of skin
      biopsies with antibodies distinguishing phosphorylated and non-phosphorylated
      human FoxO1 and FoxO3 proteins was performed before isotretinoin treatment, six
      weeks after initiation of isotretinoin therapy, and in acne-free control patients
      not treated with isotretinoin. Our in vivo study demonstrates a significant
      increase in the nucleo-cytoplasmic ratio of non-phosphorylated FoxO1 and FoxO3
      during isotretinoin treatment of acne patients. Translational and presented
      experimental evidence indicates that upregulation of nuclear FoxO1 and FoxO3
      proteins is involved in isotretinoin-induced pro-apoptotic signalling in
      sebocytes confirming the scientific hypothesis of isotretinoin-mediated
      upregulation of FoxO expression.

PMID- 30240098
TI  - Strengthening workplace well-being: perceptions of intensive care nurses.
AB  - BACKGROUND: Intensive care nursing is a professionally challenging role,
      elucidated in the body of research focusing on nurses' ill-being, including
      burnout, stress, moral distress and compassion fatigue. Although scant, research
      is growing in relation to the elements contributing to critical care nurses'
      workplace well-being. Little is currently known about how intensive care nurse
      well-being is strengthened in the workplace, particularly from the intensive care
      nurse perspective. AIMS AND OBJECTIVES: Identify intensive care nurses'
      perspectives of strategies that strengthen their workplace well-being. DESIGN: An
      inductive descriptive qualitative approach was used to explore intensive care
      nurses' perspectives of strengthening work well-being. METHOD: New Zealand
      intensive care nurses were asked to report strategies strengthening their
      workplace well-being in two free-text response items within a larger online
      survey of well-being. FINDINGS: Sixty-five intensive care nurses identified 69
      unique strengtheners of workplace well-being. Strengtheners included nurses
      drawing from personal resources, such as mindfulness and yoga. Both relational
      and organizational systems' strengtheners were also evident, including peer
      supervision, formal debriefing and working as a team to support each other.
      CONCLUSIONS: Strengtheners of intensive care nurses' workplace well-being
      extended across individual, relational and organizational resources. Actions such
      as simplifying their lives, giving and receiving team support and accessing
      employee assistance programmes were just a few of the intensive care nurses'
      identified strengtheners. These findings inform future strategic workplace well
      being programmes, creating opportunities for positive change. RELEVANCE TO
      CLINICAL PRACTICE: Intensive care nurses have a highly developed understanding of
      workplace well-being strengtheners. These strengtheners extend from the personal
      to inter-professional to organizational. The extensive range of strengtheners the
      nurses have identified provides a rich source for the development of future
      workplace well-being programmes for critical care.

PMID- 30240100
TI  - From the ADAA President.

PMID- 30240099
TI  - Recurrent solitary fibrous tumor of the breast: Magnetic resonance imaging and
      pathologic findings.

PMID- 30240102
TI  - Abstracts from the 50th Congress of the International Society of Paediatric
      Oncology (SIOP) Kyoto, Japan November 16-19, 2018.

PMID- 30240101
TI  - Risk factors for breast cancer mortality: Evidence from Brazil.

PMID- 30240103
TI  - Process of knowledge translation within routine clinical care: Implementing best
      practice in weight management.
AB  - AIM: Failure to translate research into practice is common. The present study
      implemented an evidence-based model of care to address identified evidence
      practice gaps in our department's weight management service. METHODS:
      Implementation science frameworks were used to identify barriers to best practice
      and determine appropriate strategies to overcome them. No practice change
      occurred pre-implementation. The new model of care incorporated evidence-based
      interventions into a flowchart, supported by written resources, and integrated
      routine data collection into clinic processes. Alignment with a statewide
      telephone counselling program enhanced service capacity. Data were collected for
      adult patients whose primary intervention was weight management at a South-East
      Queensland hospital and included service attendance metrics, anthropometry, diet
      quality, and interventions delivered, and were compared with guidelines. Change
      in outcomes was calculated at 3 months after initial appointments. RESULTS: Pre
      implementation, 69.2% (n = 91) of patients referred were seen by a dietitian.
      During the new model of care (n = 60), over half (63.3%) were referred to
      telephone counselling. The remainder were triaged according to the flowchart with
      100% attendance. Guideline adherence for reviews significantly increased over
      time (4.4%-50%, P < 0.001). Follow-up data were available for 31.3% and 54.5% of
      the pre-implementation and new model of care patients, respectively. No
      significant differences were observed between outcomes. CONCLUSIONS: The present
      study demonstrated successful implementation of weight management guidelines
      within routine clinical care. Following a systematic assessment of existing
      evidence-practice gaps resulted in a pragmatic evidence-based model of care that
      could be delivered within service capacity.

PMID- 30240104
TI  - Re-evaluating the nutritional awareness, knowledge and eating behaviours of women
      attending a tertiary maternity hospital following iterative service redesign.
AB  - AIM: Since the opening of the new Mater Mothers' Hospital in 2008, innovative
      initiatives were developed, implemented and evaluated to meet women's nutritional
      needs. This study evaluated changes in women's nutritional awareness, knowledge
      and behaviours and compared these data with our baseline survey. METHODS: During
      2014-2017, 421 postnatal women were surveyed across nine survey periods. Results
      were compared with those from our 2008 survey (n = 102). Surveys assessed
      nutrition knowledge, attitudes, behaviour, education preferences, and dietetic
      service awareness and were distributed on meal trays. RESULTS: A greater
      proportion of women accessed the nutrition services in 2014-2017 compared with
      2008 (19.7% vs 9.9%) and rated the resources favourably (>=3.5 out of 5). A
      similar proportion rated the importance of eating well postnatally (83.1% vs
      92.1%) and returning to their pre-pregnancy weight (62.4% vs 68.3%) as
      important/very important. In both periods, women had poor diet quality, despite
      identifying healthy eating as a high priority. A reduction in median gestational
      weight gain (GWG) approached significance, 13.0 kg (2014-2017) versus 14.0 kg
      (2008), P = 0.055. There was a significant association between GWG and cohort
      with an increase in the proportion of women gaining within their correct
      guidelines (by 15.4%), a reduction of excessive gain (by 24.7%, P < 0.001) over
      time. CONCLUSIONS: Evidence-based service changes made since 2008 have effected
      positive change in women's GWG, service preferences, and access. However, women
      still require awareness-raising and behaviour change programs to improve diet
      quality and GWG to ensure optimal pregnancy outcomes.

PMID- 30240105
TI  - Knowledge translation.

PMID- 30240106
TI  - Which comes first in human temperature regulation: the physiological or the
      behavioural response?

PMID- 30240107
TI  - Intercalation-enhanced "Click" Crosslinking of DNA.
AB  - DNA-DNA cross-linking agents constitute an important family of chemotherapeutics
      that non-specifically react with endogenous nucleophiles and therefore exhibit
      undesirable side effects. Here we report a cationic Sondheimer diyne derivative
      "DiMOC" that exhibits weak, reversible intercalation into duplex DNA (Kd =15 MUm)
      where it undergoes tandem strain-promoted cross-linking of azide-containing DNA
      to give DNA-DNA interstrand crosslinks (ICLs) with an exceptionally high apparent
      rate constant kapp =2.1*105  m-1  s-1 . This represents a 21 000-fold rate
      enhancement as compared the reaction between DIMOC and 5-(azidomethyl)-2'
      deoxyuridine (AmdU) nucleoside. As single agents, 5'-bispivaloyloxymethyl (POM)
      AmdU and DiMOC exhibited low cytotoxicity, but highly toxic DNA-DNA ICLs were
      generated by metabolic incorporation of AmdU groups into cellular DNA, followed
      by treatment of the cells with DiMOC. These results provide the first examples of
      intercalation-enhanced bioorthogonal chemical reactions on DNA, and furthermore,
      the first strain-promoted double click (SPDC) reactions inside of living cells.

PMID- 30240108
TI  - RecGwed : A probable novel regulator in the resolution of branched DNA structures
      in mycobacteria.
AB  - Structure-specific helicases, such as RecG, play an important role in the
      resolution of recombination intermediates. A bioinformatic analysis of
      mycobacterial genomes led to the identification of a protein (RecGwed ) with a C
      terminal "edge" domain, similar to the wedge domain of RecG. RecGwed is
      predominately found in the phylum Actinobacteria and in few human pathogens.
      Mycobacterium smegmatis RecGwed was able to bind branched DNA structures in vitro
      but failed to interact with single- or double-stranded DNA. The expression of
      recGwed in M. smegmatis cells was up-regulated during stationary phase/UV damage
      and down-regulated during MMS/H2 O2 treatment. These observations indicate the
      possible involvement of RecGwed in transactions during recombination events, that
      proceed though branched DNA intermediates. (c) 2018 IUBMB Life, 70(8):786-794,
      2018.

PMID- 30240110
TI  - Can invasive breast carcinoma with close or positive margins be managed without a
      new surgery?
AB  - We present the long-term outcome (FU 127 months) of a prospective study with 248
      breast cancer patients with close or positive surgical margin, treated with 50 Gy
      whole breast irradiation plus high-dose-rate boost, 3 * 4.4 Gy. Actuarial breast
      failure at 10/15 years was 6.5%/11.6%; with positive margin (120) 6.8%/14.8%,
      with margin <=2 mm (76) 9.8%/9.8%, with margin >2 mm <5 mm (52) 2%/2%. In 90
      patients aged <=50 was 11.9%/17.8%, between 51 and 70, 3.8%/8.2%, >70, 0%.
      Fibrosis appeared in 26.7%. Cosmetic outcome was excellent/good in 85.8%. This
      approach avoids a second surgery in women >50 with positive surgical margin, or
      with close margins in all ages.

PMID- 30240111
TI  - Beyond 2D: 3D bioprinting for skin regeneration.
AB  - Essential cellular functions that are present in tissues are missed by two
      dimensional (2D) cell monolayer culture. It certainly limits their potential to
      predict the cellular responses of real organisms. Engineering approaches offer
      solutions to overcome current limitations. For example, establishing a three
      dimensional (3D)-based matrix is motivated by the need to mimic the functions of
      living tissues, which will have a strong impact on regenerative medicine.
      However, as a novel approach, it requires the development of new standard
      protocols to increase the efficiency of clinical translation. In this review, we
      summarised the various aspects of requirements related to well-suited 3D
      bioprinting techniques for skin regeneration and discussed how to overcome
      current bottlenecks and propel these therapies into the clinic.

PMID- 30240112
TI  - Cleft palate and hypopituitarism in a patient with Noonan-like syndrome with
      loose anagen hair-1.
AB  - Noonan syndrome (NS), the most common of the RASopathies, is a developmental
      disorder caused by heterozygous germline mutations in genes encoding proteins in
      the RAS-MAPK signaling pathway. Noonan-like syndrome with loose anagen hair
      (NSLH, including NSLH1, OMIM #607721 and NSLH2, OMIM #617506) is characterized by
      typical features of NS with additional findings of macrocephaly, loose anagen
      hair, growth hormone deficiency in some, and a higher incidence of intellectual
      disability. All NSLH1 reported cases to date have had an SHOC2 c.4A>G, p.Ser2Gly
      mutation; NSLH2 cases have been reported with a PPP1CB c.146G>C, p.Pro49Arg
      mutation, or c.166G>C, p.Ala56Pro mutation. True cleft palate does not appear to
      have been previously reported in individuals with NS or with NSLH. While some
      patients with NS have had growth hormone deficiency (GHD), other endocrine
      abnormalities are only rarely documented. We present a female patient with NSLH1
      who was born with a posterior cleft palate, micrognathia, and mild hypotonia.
      Other findings in her childhood and young adulthood years include hearing loss,
      strabismus, and hypopituitarism with growth hormone, thyroid stimulating hormone
      (TSH), and gonadotropin deficiencies. The SHOC2 mutation may be responsible for
      this patient's additional features of cleft palate and hypopituitarism.

PMID- 30240113
TI  - Spectrally and spatially resolved laser-induced photobleaching of endogenous
      flavin fluorescence in cardiac myocytes.
AB  - Naturally occurring endogenous fluorescence of flavins, arising in response to
      excitation by visible light, offers broad opportunity to investigate
      mitochondrial metabolic state directly in living cells and tissues, including in
      clinical settings. However, photobleaching, the loss of the autofluorescence
      intensity following prolonged exposure to light is an inherent phenomenon
      occurring during the fluorescence acquisition, which can have a negative impact
      on the recorded data, particularly in the context of measurement of metabolic
      modulations in pathophysiological conditions. In the presented study, we present
      a detailed analysis of endogenous flavins fluorescence photobleaching arising in
      living cardiac cells during spectrally-resolved confocal imaging. We demonstrate
      significant nonuniform photobleaching related to different bleaching rates of
      individual flavin components, resolved by linear spectral unmixing of the
      recorded signals. Induced photodamage was without effect on the cell morphology,
      but lead to significant modifications of the cell responsiveness to metabolic
      modulators and its contractility, suggesting functional metabolic alterations in
      the recorded cells. These findings point to the necessity of inducing limited
      photobleaching during metabolic screening in all studies involving visible light
      excitation and fluorescence acquisition in living cells.

PMID- 30240114
TI  - Using noninvasive metagenomics to characterize viral communities from wildlife.
AB  - Microbial communities play an important role in organismal and ecosystem health.
      While high-throughput metabarcoding has revolutionized the study of bacterial
      communities, generating comparable viral communities has proven elusive,
      particularly in wildlife samples where the diversity of viruses and limited
      quantities of viral nucleic acid present distinctive challenges. Metagenomic
      sequencing is a promising solution for studying viral communities, but the lack
      of standardized methods currently precludes comparisons across host taxa or
      localities. Here, we developed an untargeted shotgun metagenomic sequencing
      protocol to generate comparable viral communities from noninvasively collected
      faecal and oropharyngeal swabs. Using samples from common vampire bats (Desmodus
      rotundus), a key species for virus transmission to humans and domestic animals,
      we tested how different storage media, nucleic acid extraction procedures and
      enrichment steps affect viral community detection. Based on finding viral
      contamination in foetal bovine serum, we recommend storing swabs in RNAlater or
      another nonbiological medium. We recommend extracting nucleic acid directly from
      swabs rather than from supernatant or pelleted material, which had undetectable
      levels of viral RNA. Results from a low-input RNA library preparation protocol
      suggest that ribosomal RNA depletion and light DNase treatment reduce host and
      bacterial nucleic acid, and improve virus detection. Finally, applying our
      approach to twelve pooled samples from seven localities in Peru, we showed that
      detected viral communities saturated at the attained sequencing depth, allowing
      unbiased comparisons of viral community composition. Future studies using the
      methods outlined here will elucidate the determinants of viral communities across
      host species, environments and time.

PMID- 30240115
TI  - Modulating Self-Assembly of DNA Crystals with Rationally Designed Agents.
AB  - This manuscript reports a strategy for controlling the crystallization kinetics
      and improving the quality of engineered self-assembled 3D DNA crystals. Growing
      large, high-quality biomacromolecule crystals is critically important for
      determining the 3D structures of biomacromolecules. It often presents a great
      challenge to structural biologists. Herein, we introduce a rationally designed
      agent to modulate the crystallization process. Under such conditions, fewer, but
      larger, crystals that yield diffraction patterns of modestly higher resolution
      are produced compared with the crystals from conditions without the modulating
      agent. We attribute the improvement to a smaller number of nuclei and slow growth
      rate of crystallization. This strategy is expected to be generally applicable for
      crystallization of other biomacromolecules.

PMID- 30240116
TI  - An Innovative Rescue Surgical Procedure for Early Onset Hepatic Venous Outflow
      Obstruction After Pediatric Living Donor Liver Transplantation.

PMID- 30240117
TI  - Canavalia ensiformis-derived lectin inhibits biofilm formation of
      enterohemorrhagic Escherichia coli and Listeria monocytogenes.
AB  - AIM: A lectin Concanavalin A (ConA) derived from Canavalia ensiformis (jack bean)
      exhibits high-binding affinity to carbohydrates on bacterial cell surfaces. The
      objective of this study was to inhibit the biofilm formation of the foodborne
      pathogens enterohemorrhagic Escherichia coli and Listeria monocytogenes using
      ConA prepared by a membrane-based extraction method. METHODS AND RESULTS: ConA
      was extracted using a simple and inexpensive membrane method instead of a
      chromatography approach. The extracted ConA was effective in inhibiting biofilms
      of E. coli by 30-fold and L. monocytogenes by 140-fold. In addition, ConA
      decreased the swimming motility of enterohemorrhagic E. coli EDL933 (EHEC) by
      37%, resulting in low biofilm formation, as ConA binding to the bacterial cell
      surfaces might cause a reduced capability to adhere due to low cellular motility.
      We confirmed that the extracted ConA contains active components at less than 10
      kDa as well as ConA multimers (>30 kDa) that repress EHEC biofilms. Additionally,
      noncell-based mannose reduced the activity of ConA in inhibiting biofilms.
      CONCLUSIONS: ConA extracted using the membrane-based method is active in
      inhibiting the biofilm formation by E. coli and L. monocytogenes via the mannose
      binding affinity of ConA. SIGNIFICANCE AND IMPACT OF THE STUDY: ConA can be used
      as a promising anti-adherent and antibiofilm agent in inhibiting biofilm
      formation by enterohemorrhagic E. coli and L. monocytogenes. The membrane-based
      extraction approach may be applied for the economic production of biologically
      active lectins.

PMID- 30240118
TI  - Risk of Down syndrome birth: Consanguineous marriage is associated with maternal
      meiosis-II nondisjunction at younger age and without any detectable recombination
      error.
AB  - Consanguineous marriage was examined as a risk factor for Down syndrome birth. We
      genotyped Down syndrome family trios using short tandem repeat markers on 21q-to
      interpret the parental and meiotic stage of origin of errors as well as to record
      recombination profile along long arm of chromosome 21. We then compared
      nonconsanguineous (N = 811) group with-the consanguineous (N =157) marriages. We
      report for the first time that consanguineous marriage is associated with an
      increased risk for nondisjunction of chromosome 21 in oocytes-during the second
      meiotic division. We observed the absence of recombination more frequently in
      younger mothers in nonconsanguineous meiosis I cases. This was in contrast to an
      equal distribution of nonrecombinant cases across the age categories in the
      meiosis I consanguineous group. Moreover, the non-consanguineous group exhibited
      preferential telomeric recombination in meiosis I error among younger women and
      centromeric recombination in meiosis II errors in older women. In contrast, the
      consanguineous group exhibited medially placed recombination events in both
      meiosis I and meiosis II nondisjunction errors. Additionally, we recorded reduced
      maternal age at conception in the-consanguineous group. These findings suggest
      novel risk factors associated that increase the risk of chromosome 21
      nondisjunction in the families with consanguinity.

PMID- 30240119
TI  - A novel de novo mutation p.Ala428Asp in KRT5 gene as a cause of localized
      epidermolysis bullosa simplex.
AB  - Epidermolysis bullosa is a group of inherited blistering skin diseases resulting
      in most cases from missense mutations in KRT5 and KRT14 genes encoding the basal
      epidermal keratins 5 and 14. Here, we present a patient diagnosed with a
      localized subtype of epidermolysis bullosa simplex caused by a heterozygous
      mutation p.Ala428Asp in the KRT5 gene, that has not been previously identified.
      Moreover, a bioinformatic analysis of the novel mutation was performed, showing
      changes in the interaction network between the proteins.Identification of novel
      mutations and genotype-phenotype correlations allow to better understanding of
      underlying pathophysiologic bases and is important for genetic counseling,
      patients management, and disease course prediction. This article is protected by
      copyright. All rights reserved.

PMID- 30240120
TI  - A dedicated target capture approach reveals variable genetic markers across micro
      and macro-evolutionary time scales in palms.
AB  - Understanding the genetics of biological diversification across micro- and macro
      evolutionary time scales is a vibrant field of research for molecular ecologists
      as rapid advances in sequencing technologies promise to overcome former
      limitations. In palms, an emblematic, economically and ecologically important
      plant family with high diversity in the tropics, studies of diversification at
      the population and species levels are still hampered by a lack of genomic markers
      suitable for the genotyping of large numbers of recently diverged taxa. To fill
      this gap, we used a whole genome sequencing approach to develop target sequencing
      for molecular markers in 4,184 genome regions, including 4,051 genes and 133 non
      genic putatively neutral regions. These markers were chosen to cover a wide range
      of evolutionary rates allowing future studies at the family, genus, species and
      population levels. Special emphasis was given to the avoidance of copy number
      variation during marker selection. In addition, a set of 149 well-known sequence
      regions previously used as phylogenetic markers by the palm biological research
      community were included in the target regions, to open the possibility to combine
      and jointly analyse already available data sets with genomic data to be produced
      with this new toolkit. The bait set was effective for species belonging to all
      three palm sub-families tested (Arecoideae, Ceroxyloideae and Coryphoideae), with
      high mapping rates, specificity and efficiency. The number of high-quality single
      nucleotide polymorphisms (SNPs) detected at both the sub-family and population
      levels facilitates efficient analyses of genomic diversity across micro- and
      macro-evolutionary time scales.

PMID- 30240122
TI  - Erratum.

PMID- 30240123
TI  - Corrigendum.

PMID- 30240121
TI  - STACKing the odds for adolescent survival: health service factors associated with
      full retention in care and adherence amongst adolescents living with HIV in South
      Africa.
AB  - INTRODUCTION: There are two million HIV-positive adolescents in southern Africa,
      and this group has low retention in care and high mortality. There is almost no
      evidence to identify which healthcare factors can improve adolescent self
      reported retention. This study examines factors associated with retention amongst
      antiretroviral therapy (ART)-initiated adolescents in South Africa. METHODS: We
      collected clinical records and detailed standardized interviews (n = 1059) with
      all 10- to 19 year-olds ever initiated on ART in all 53 government clinics of a
      health subdistrict, and community traced to include lost-to-follow-up (90.1% of
      eligible adolescents interviewed). Associations between full self-reported
      retention in care (no past-year missed appointments and 85% past-week adherence)
      and health service factors were tested simultaneously in sequential multivariate
      regression and marginal effects modelling, controlling for covariates of age,
      gender, urban/rural location, formal/informal housing, maternal and paternal
      orphanhood, vertical/horizontal HIV infection, overall health, length of time on
      ART and type of healthcare facility. RESULTS: About 56% of adolescents had self
      reported retention in care, validated against lower detectable viral load (AOR:
      0.63, CI: 0.45 to 0.87, p = 0.005). Independent of covariates, five factors
      (STACK) were associated with improved retention: clinics Stocked with medication
      (OR: 3.0, CI: 1.6 to 5.5); staff with Time for adolescents (OR: 2.7, CI: 1.8 to
      4.1); adolescents Accompanied to the clinic (OR: 2.3, CI: 1.5 to 3.6); enough
      Cash to get to clinic safely (OR: 1.4, CI: 1.1 to 1.9); and staff who are Kind
      (OR: 2.6, CI: 1.8 to 3.6). With none of these factors, 3.3% of adolescents
      reported retention. With all five factors, 69.5% reported retention. CONCLUSIONS:
      This study identifies key intervention points for adolescent retention in HIV
      care. A basic package of clinic and community services has the potential to STACK
      the odds for health and survival for HIV-positive adolescents.

PMID- 30240124
TI  - Serum cholinesterase activity is elevated in female diarrhea-predominant
      irritable bowel syndrome patients compared to matched controls.
AB  - BACKGROUND: Micro-inflammation is involved in the pathogenesis of irritable bowel
      syndrome (IBS). The parasympathetic nervous system, via acetylcholine (ACh), and
      its hydrolytic enzymes, plays a role in regulating inflammation. Increased serum
      cholinesterase activity, named cholinergic Status (CS), is associated with
      decreased inflammatory inhibition (ie, pro-inflammation). We assessed the
      association between IBS diarrhea-predominant (IBS-D) symptoms, CS, and
      inflammatory biomarkers. METHODS: Women with IBS-D were prospectively recruited.
      Serum acetylcholinesterase (AChE), CS, and high-sensitivity C-reactive protein
      (hs-CRP) levels were analyzed and fecal calprotectin (FC) in a subgroup of
      patients. The control group included women attending routine health checkups
      (matched by age and BMI). KEY RESULTS: Ninety-four women with IBS-D were compared
      to matched controls (1:1). Serum CS, AChE, and the AChE/butyrylcholinesterase
      (BChE) ratios were significantly increased in the IBS-D group compared to matched
      controls (P = 0.018, P = 0.001, and P = 0.004, respectively). Using a multiple
      logistic regression model, IBS-D was almost twice as likely in women with high CS
      compared to women with low CS (adjusted OR=1.84 (95% CI: 1.01-3.33), P = 0.045).
      Furthermore, IBS-D patients with higher hs-CRP levels demonstrated lower CS and
      BChE activity and elevated AChE and AChE/BChE ratios compared to patients with
      lower hs-CRP levels (P = 0.026, P = 0.036, P = 0.002; and P = 0.0007,
      respectively). CS was not correlated with the IBS symptoms score. CONCLUSIONS AND
      INFERENCES: This is the first study to explore the potential role of serum CS in
      IBS-D. The findings emphasize the possible role of the autonomic nervous system
      and its anti-inflammatory properties in IBS.

PMID- 30240126
TI  - Epidemiological study of burn patients hospitalised at a burns centre, Manipal.
AB  - Burn injuries constitute a major public health problem and account for a
      significant cause of mortality and morbidity amongst the Indian population. This
      2-year prospective study was undertaken to find out the exact epidemiological
      determinants of 737 patients admitted with burn injuries and, thus, to try and
      formulate effective preventive strategies. This study was conducted in the
      department of plastic surgery and burns from September 2011 to June 2013. All
      consecutive patients with major burns admitted for in-hospital treatment during
      the study period were included in the study. The data collected included age,
      gender, cause and mode of burns, total burn surface area (TBSA), microbiological
      profile and outcome. More than 55% of the patients were female (58.61%). The mean
      age was 31.3 years ranging from 8 months to 89 years. A higher number of females
      (97.5%) sustained burn injuries at home compared with 36.11% males sustaining
      injuries outdoors. (P = 0.000). Almost one third of injuries (40.36%) occurred
      between 4 pm and 8 pm, followed by 28% between 7 am and 12 noon. Synthetic
      garments were worn by 70% of females at the time of injury, whereas 40% of males
      had worn mixed clothing (P = 0.000). Flame injuries contributed to 80.1% of burns
      in females (P = 0.006). The rate of electrical injuries (9.8%) was significantly
      higher in males (P = 0.005). In almost 40% of males, TBSA was <19%, whereas in
      40% of females, TBSA was >68%. (P = 0.004). Microbial profile showed that
      pseudomonas aeruginosa (n = 260; 35.3%), Klebsiella pneumoniae (n = 209; 28.5%),
      and Escherichia coli (n = 145; 22.6%) were the most frequent types of
      Staphylococci bacterial growths. The cause for burn injury was ignition of
      clothes in 68.74% females, and in 35.48% males, it was because of an attempt to
      save other burn injury victims (P = 0.013) The case fatality rate was 29.3%. A
      majority of the males (60.7%) recovered, whereas 45.89% of females succumbed
      because of their burn injury. (P = 0.001). As the aetiological factors of burn
      injuries vary considerably in different communities, careful study of the pattern
      in every community is needed before a sound prevention programme can be planned
      and implemented. Hence, this study was conducted to assess epidemiological,
      modes, causes, and risk factors and the microbial profile of burn injuries and to
      study the outcomes.

PMID- 30240125
TI  - Improved Imaging of Zebrafish Motility.
AB  - Zebrafish larvae are transparent and the entire gastrointestinal (GI) tract is
      easily visualized. Application of a new image analysis technique is reported in
      this issue of Neurogastroenterology and Motility (Neurogastroenterol Motil.,
      2018, volume 30, e13351). The technique quantifies movement in images collected
      in a timed sequence, and characterizes smooth muscle contractions based on
      contraction distance and frequency. The technique also reports the contraction
      amplitude, or the distance moved. This technique, and current spatiotemporal
      mapping techniques, are essential tools enabling characterization of GI motility
      patterns in intact physiological settings. Advances and development of transgenic
      zebrafish that lack pigmentation, with calcium reporters expressed in specific
      cell types, or with inactivation of specific genes contribute to our
      understanding of the generation, and regulation of GI motility at the molecular,
      cellular, and systemic level. Finally, development of chambers that immobilize
      zebrafish larvae for long-duration imaging will contribute to our technique
      toolbox, and will provide an increased experimental throughput.

PMID- 30240127
TI  - The direct cost of pressure injuries in an Australian residential aged care
      setting.
AB  - Pressure injuries have a negative effect on well-being and the cost of treatment
      places a significant burden on the health care system. Research has, however,
      tended to extrapolate or estimate the cost of pressure injuries resulting in
      uncertainty regarding the true cost of this condition. The aim of this
      prospective observational study was to quantify the cost of pressure injury
      treatment in the Australian residential aged care setting. An electronic health
      care record audit and observation of usual pressure injury treatment was
      undertaken with a sample of 20 participants who had 23 pressure injuries. The
      actual treatment cost, an evidence-based practice model cost, and a projected
      treatment cost were calculated. The overall cost of pressure injury treatment was
      AU$98,489.22. The average daily cost by pressure injury stage was AU$26.42 for a
      Stage 1 pressure injury, AU$37.17 for a Stage 2 pressure injury, AU$30.01 for a
      Stage 3 pressure injury, and AU$10.22 for an Unstageable pressure injury. The
      projected cost of treatment was AU$104,510.41. At 42 days this cost extended to
      AU$116,552.79. This study has quantified the cost of pressure injury treatment in
      a residential aged care setting. The study may inform future efforts to
      accurately calculate the cost of PIs and the effectiveness of strategies to
      reduce the economic burden of this condition.

PMID- 30240128
TI  - The 18th Congress of Gastroenterology China, 27-29 September 2018, Dalian, China.

PMID- 30240129
TI  - Symbiotic fungal endophyte Phomopsis liquidambari-rice system promotes nitrogen
      transformation by influencing below-ground straw decomposition in paddy soil.
AB  - AIMS: To explore if and how symbiotic Phomopsis liquidambari-rice system
      influences below-ground straw decomposition and then nitrogen(N) transformation
      in response to environmental N levels. METHODS AND RESULTS: Litter bag
      experiments were utilized to trace the decay process during rice growth phases
      (seedling (T1), tillering (T2), heading (T3) and maturing (T4) stage), with (E+)
      and without endophyte (E-), under low (LN), medium (MN) and high nitrogen (HN)
      supply. Litter, soil and plant samples were collected to evaluate the decay
      process, N transformations, plant quality and relative abundance of soil ammonia
      oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB) and P. liquidambari.
      The results showed that straw decomposition increased by 19.76% (LN, T2 stage),
      14.05% (MN, T3 stage) and 16.88% (MN, T4 stage) in E+ pots when compared with E-
      pots. Further analysis revealed that no significant endophyte * N interaction was
      found for straw decay rate and that the decay rate was reduced by a higher N
      supply (LN, 37.16 +/- 0.65%; MN, 32.27 +/- 1.72%; HN, 29.44 +/- 1.22%) at the T1
      stage, whereas straw decay rate and N release increased by 9.38 and 11.16%,
      respectively, mainly by endophyte colonization at the T4 stage. The abundance of
      AOA and AOB were altered, corresponding with the decay rate. Soil mineral N,
      straw mineral N and plant quality were shown to increase in E+ pots, depending on
      environmental N conditions and growth phase. The yield increased by 2.98% for E+
      plants under MN level. CONCLUSIONS: Symbiotic P. liquidambari-rice system
      promoted below-ground straw decomposition and N transformation, depending on
      environmental N levels and plant growth phase. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study provides evidence that fungal endophyte-plant systems are able
      to promote N transformation by increasing straw decomposition. A reasonable
      combination of N inputs could enhance its advantage in agriculture ecosystems.

PMID- 30240130
TI  - Predictive Value of Intraoperative Pulmonary Vascular Resistance in Liver
      Transplantation.
AB  - We aimed to evaluate the association between intraoperative pulmonary vascular
      resistance (PVR) and clinical outcome of liver transplantation (LT).
      Cardiovascular involvement of end-stage liver disease is relatively common, and
      hemodynamic instability during LT can be fatal to recipients. However, the
      clinical impact of intraoperative PVR in LT remains undetermined. A total of 363
      adult recipients with intraoperative right heart catheterization from January
      2011 to May 2016 were analyzed. Patients were divided into 2 groups according to
      PVR. Two separate analyses were performed according to the time point of
      measurement: at the beginning and at the end of LT. The primary outcome was all
      cause death or graft failure during the follow-up period. Increased PVR was
      observed in 11.8% (43/363) of recipients at the beginning and 12.7% (46/363) of
      recipients at the end of LT. PVR at the beginning of LT had no significant effect
      on the rate of death or graft failure in the multivariate analysis (hazard ratio
      [HR], 1.24; 95% confidence interval [CI], 0.64-2.38; P = 0.52). In contrast, PVR
      at the end of LT was significantly associated with death or graft failure during
      the overall follow-up period (HR, 2.00; 95% CI, 1.13-3.54; P = 0.02). In
      conclusion, PVR at the end of LT, rather than the beginning, is associated with
      clinical outcome. Larger trials are needed to support this finding.

PMID- 30240131
TI  - Pupilloplasty by radiofrequency diathermy.
AB  - PURPOSE: Several methods have been reported to treat pupil deformities. However,
      there are some disadvantages to these methods. Here, we introduce the new
      technique of pupilloplasty. METHODS: We retrospectively collected five patients
      who underwent pupilloplasty by radiofrequency diathermy (RFD) in eyes with acorea
      or a severe pupillary fibrous membrane. The RFD tip was inserted into the
      anterior chamber after injection of an ophthalmic viscosurgical device (OVD). It
      was then used to resect the iris and fibrous membrane around the pupillary centre
      to restore a centred and round pupil. RESULTS: No obvious bleeding was observed
      during resection of the iris or fibrous membrane with the RFD technique. All
      cases were successfully treated, and pupil transparency was restored. CONCLUSION:
      We introduced a new technique of pupilloplasty by RFD that is easily manageable,
      reduces bleeding, and is suitable for most types of pupillary seclusion,
      especially for acorea and severe pupillary fibrous membrane.

PMID- 30240132
TI  - Pharmacokinetics and Safety of CSL112 (Apolipoprotein A-I [Human]) in Adults With
      Moderate Renal Impairment and Normal Renal Function.
AB  - CSL112 (Apolipoprotein A-I [human]) is an intravenous preparation of
      apolipoprotein A-I (apoA-I), formulated with phosphatidylcholine (PC) and
      stabilized with sucrose, in development to prevent early recurrent cardiovascular
      events following acute myocardial infarction (AMI). This phase 1 study was
      designed to determine if moderate renal impairment (RI) influenced the
      pharmacokinetics (PK) and safety of CSL112. Thirty-two subjects, 16 with moderate
      RI (estimated glomerular filtration rate [eGFR] >= 30 and < 60 mL/min/1.73 m2 )
      and 16 age-, sex-, and weight-matched subjects with normal renal function (eGFR
      >= 90 mL/min/1.73 m2 ) were randomized 3:1 to receive a single infusion of CSL112
      2 g (n = 6) or placebo (n = 2), or CSL112 6 g (n = 6) or placebo (n = 2). PK
      sampling was at prespecified times from 48 hours prior to 144 hours following
      infusions, with final safety assessments at 90 days. Renal and hepatic safety,
      and adverse events (AEs) were monitored throughout the study. Plasma apoA-I and
      PC PK profiles were similar between renal function cohorts at both doses. For
      CSL112 6 g mean +/- SD apoA-I AUC0-last was 7670 +/- 1900 and 9170 +/- 2910
      mg.h/dL in normal renal function and moderate RI subjects, respectively. Renal
      apoA-I clearance was <1% of CSL112 dose. In moderate RI, sucrose clearance was
      slower; however, approximately 70% was excreted within 48 hours in both renal
      function cohorts. No CSL112-related serious AEs or clinically significant renal
      or hepatic safety changes were observed. Dose adjustment of CSL112 is not
      required in subjects with moderate RI, supporting its further investigation in
      AMI patients with moderate RI.

PMID- 30240133
TI  - Varicella zoster reactivation immediately following keystone flap reconstruction
      of a radiated back wound.

PMID- 30240135
TI  - Biomass Sucrose-Derived Cobalt@Nitrogen-Doped Carbon for Catalytic Transfer
      Hydrogenation of Nitroarenes with Formic Acid.
AB  - Fabrication of non-noble metal-based heterogeneous catalysts by a facile and cost
      effective strategy for ecofriendly catalytic transfer hydrogenation (CTH) is of
      great significance for organic transformations. A cobalt@nitrogen-doped carbon
      (Co@NC) catalyst was prepared from renewable biomass-derived sucrose, harmless
      melamine, and earth-abundant Co(AcO)2 as the precursor materials by hydrothermal
      treatment and carbonization. Co nanoparticles (NPs) were coated with NC shells
      and uniformly embedded in the NC framework. The as-obtained Co@NC-600 (carbonized
      at 600  degrees C) catalyst exhibited excellent catalytic efficiency for CTH of
      various functionalized nitroarenes with formic acid (FA) as hydrogen donor in
      aqueous solution. The uniformly incorporated N atoms in the C matrix and the
      encapsulated Co NPs showed synergistic effects in the CTH reactions. A
      mechanistic analysis indicated that the protons from FA were activated by Co
      sites after being captured by N atoms, and then reacted with nitroarenes adsorbed
      on the surface of the catalysts to generate the corresponding aromatic amines.
      Moreover, the catalyst showed excellent durability and reusability without
      obvious decrease in activity even after five reaction cycles. Thus, the study
      reported herein provides a cost-effective, sustainable strategy for fabrication
      of biomass-derived non-noble metal-based catalysts for green and efficient
      catalytic transformations.

PMID- 30240134
TI  - Morpho-Functional Characteristics of Bone Marrow Multipotent Mesenchymal Stromal
      Cells after Activation or Inhibition of Epidermal Growth Factor and Toll-Like
      Receptors or Treatment with DNA Intercalator Cisplatin.
AB  - This study is aimed to reveal morphological and functional changes in multipotent
      mesenchymal stromal cells (MSCs) isolated from the rat bone marrow after: (i)
      activation of Toll-like receptors (TLRs) with teichoic acid (TA), (ii) impact on
      epidermal growth factor (EGF) receptors with activator EGF or inhibitor
      Herceptin, and (iii) treatment with DNA intercalator Cisplatin. According to our
      results, TA and EGF cause an increase in the synthesis of glycosaminoglycans, c
      Myc content, and protein in the MSC cytoplasm. It was observed that the cell
      population in G0 phase decreased and the cell population in G1 phase increased,
      when compared with control. At the same time, the cell population with a higher
      nuclear-cytoplasmic ratio (NCR) in S and G2 phases also increased. This indicates
      the manifestation of the MSC mesenchymal phenotype, exhibiting indirect metabolic
      signs of the regenerative potential increase. In other experiments, Herceptin was
      shown to suppress only the stemness signs of MSCs, while Cisplatin seriously
      affected cell viability in general, reducing synthetic and proliferative
      activities and causing cell morphology disturbances.

PMID- 30240136
TI  - Something special about CO-dependent CO2 fixation.
AB  - Carbon dioxide enters metabolism via six known CO2 fixation pathways, of which
      only one is linear, exergonic in the direction of CO2 -assimilation, and present
      in both bacterial and archaeal anaerobes - the Wood-Ljungdahl (WL) or reductive
      acetyl-CoA pathway. Carbon monoxide (CO) plays a central role in the WL pathway
      as an energy rich intermediate. Here, we scan the major biochemical reaction
      databases for reactions involving CO and CO2 . We identified 415 reactions
      corresponding to enzyme commission (EC) numbers involving CO2 , which are non
      randomly distributed across different biochemical pathways. Their taxonomic
      distribution, reversibility under physiological conditions, cofactors and
      prosthetic groups are summarized. In contrast to CO2 , only 15 reaction classes
      involving CO were detected. Closer inspection reveals that CO interfaces with
      metabolism and the carbon cycle at only two enzymes: anaerobic carbon monoxide
      dehydrogenase (CODH), a Ni- and Fe-containing enzyme that generates CO for CO2
      fixation in the WL pathway, and aerobic CODH, a Mo- and Cu-containing enzyme that
      oxidizes environmental CO as an electron source. The CO-dependent reaction of the
      WL pathway involves carbonyl insertion into a methyl carbon-nickel at the Ni-Fe-S
      A-cluster of acetyl-CoA synthase (ACS). It appears that no alternative mechanisms
      to the CO-dependent reaction of ACS have evolved in nearly 4 billion years,
      indicating an ancient and mechanistically essential role for CO at the onset of
      metabolism.

PMID- 30240137
TI  - Optic nerve head morphology in primary open-angle glaucoma and nonarteritic
      anterior ischaemic optic neuropathy measured with spectral domain optical
      coherence tomography.
AB  - PURPOSE: Optic nerve head (ONH) parameters as well as circumpapillary retinal
      nerve fibre layer (RNFL) thickness values measured with two different spectral
      domain optical coherence tomography (SD-OCT) machines (Spectralis(r) and
      Cirrus(r) OCT) have been compared between two patient groups, primary open-angle
      glaucoma (POAG), nonarteritic anterior ischaemic optic neuropathy (NAION) and
      healthy controls. A comparison of the performance of the two OCT machines was
      made. METHODS: Twenty healthy controls, 20 POAG and 20 NAION patients with
      comparable visual field defects were included. Comparison between groups was made
      using anova and post hoc t-tests. To evaluate the diagnostic power of OCT to
      differentiate POAG from NAION, a stepwise linear regression analysis of the rim
      RNFL correlation with adjusting covariates (optic disc area and age) was
      performed. Based on the regression formula, the area under the receiver operator
      characteristic (AUROC) was calculated. RESULTS: Both glaucoma and NAION patients
      showed significantly smaller global RNFL thickness values compared to healthy
      subjects in t-tests (p < 0.001), while only patients with glaucoma showed
      significantly smaller global ONH parameters for both devices compared to healthy
      subjects (p < 0.001). Correlation between global ONH parameters was highly
      statistically significant (r = 0.93), whereas in t-test a statistically
      significant difference between the two machines was detected (p < 0.001). Area
      under the receiver operator characteristic revealed a similarly good
      discrimination between glaucoma and NAION for Spectralis(r) (0.980) and Cirrus(r)
      OCT (0.945). CONCLUSION: NAION patients have similar RNFL thickness values as do
      glaucomatous eyes, whereas ONH parameters in NAION eyes were similar to those
      seen in healthy controls. This difference might help discriminating between these
      two different disease conditions in a chronic disease stadium, and in this
      regard, none of the two OCT machines performed better.

PMID- 30240138
TI  - Intensity-modulated radiotherapy is a safe and effective treatment for localized
      malignant pleural mesothelioma.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare disease and management
      of localized disease is controversial. Radiotherapy has been shown to be useful
      after extrapleural pneumonectomy (EPP), as well as with less aggressive surgery.
      As no reports of the treatment of this disease have ever been published from
      Israel, we report our experience with MPM and intensity-modulated radiotherapy
      (IMRT). METHODS: The complete medical records of patients treated for MPM at the
      Rabin Medical Center from 1 August 2007 to 31 March 2016 were reviewed. Twenty
      seven patients were treated with IMRT, either post-EPP or without EPP. Patients
      received 54 Gy in 2 Gy fractions using the restricted field IMRT technique.
      Chemotherapy was administered sequentially in 26% of patients. Patients were
      followed up from the date of diagnosis to death or treatment failure. RESULTS:
      Seventy-eight percent of patients had the epithelioid subtype. Nearly all
      patients were male (85%) and 90% of non-surgical patients were administered
      chemotherapy compared to 56% of post-EPP patients. All patients completed therapy
      and only 16% had grade 1-2 radiation pneumonitis, with no incidence of grade 3 or
      higher. The median follow-up was 22 months and the mean overall survival was 34.9
      months. The mean time to progression following radiation therapy was 26.7 months.
      The mean time to local and distant failure was 19 and 16 months, respectively.
      CONCLUSIONS: IMRT for localized pleural mesothelioma is a tolerable and effective
      therapy both post-EPP or without surgery. These results suggest that future
      investigation in this area is required.

PMID- 30240139
TI  - The acute blood pressure-lowering effect of amiloride is independent of
      endothelial ENaC and eNOS in humans and mice.
AB  - AIMS: The epithelial sodium channel (ENaC) is expressed in cultured endothelial
      cells and inhibitory coupling to eNOS activity has been proposed. The present
      study tested the hypothesis that ENaC blockers increase systemic NO-products and
      lower blood pressure in patients and mice, depending on eNOS. METHODS: NO
      products and cGMP were measured in diabetes patient urine and plasma samples
      before and after amiloride treatment (20-40 mg for two days, plasma n = 22, urine
      n = 12 and 5-10 mg for eight weeks, plasma n = 52, urine n = 55). Indwelling
      catheters were implanted in the femoral artery and vein in mice for continuous
      arterial blood pressure and heart rate recordings and infusion. RESULTS:
      Treatment with amiloride for two days increased plasma and urine NO-products,
      while plasma cGMP decreased and urinary cGMP was unchanged in patient samples.
      Eight weeks of treatment with amiloride did not alter NO-products and cGMP. In
      mice, amiloride boli of 5, 50, and 500 ug/kg lowered heart rate and arterial
      blood pressure significantly and acutely. Benzamil had no effect on pressure and
      raised heart rate. In hypertensive eNOS-/- and L-NAME-treated mice, amiloride
      lowered blood pressure significantly. L-NAME infusion significantly decreased NO
      products in plasma; amiloride and eNOS-deletion had no effect. An acetylcholine
      bolus resulted in acute blood pressure drop that was attenuated in eNOS-/- and L
      NAME mice. ENaC subunit expressions were not detected consistently in human and
      mouse arteries and endothelial cells. CONCLUSION: Amiloride has an acute
      hypotensive action not dependent on ENaC and eNOS and likely related to the
      heart.

PMID- 30240140
TI  - An autopsy report of three kindred in a Gerstmann-Straussler-Scheinker disease
      P105L family with a special reference to prion protein, tau, and beta-amyloid.
AB  - INTRODUCTION: Gerstmann-Straussler-Scheinker disease P105L (GSS105) is a rare
      variant of GSS caused by a point mutation of the prion protein (PrP) gene at
      codon 105 (proline to leucine substitution). It is clinically characterized by
      spastic paraparesis and dementia and histopathologically defined by PrP-plaques
      in the brain. This report describes a clinicopathological analysis of three
      autopsied kindred from a Japanese GSS105 family, plus a topological analysis of
      PrP, hyperphosphorylated tau (p-tau), and beta-amyloid (Abeta). METHODS: Using
      paraffin-embedded sections, we applied histology and single- and multiple
      labeling immunohistochemistry for PrP, p-tau, and Abeta to the three cases.
      Comparative semi-quantitative analyses of tissue injuries and PrP-plaques were
      also employed. RESULTS: Case 1 (45 years old (yo)) and Case 2 (56 yo) are
      sisters, and Case 3 (49 yo) is the son of Case 2. Case 1 and Case 2 presented
      with spastic paraparesis followed by dementia, whereas Case 3 presented, not with
      spastic paraparesis, but with psychiatric symptoms. In Case 1 and Case 2, the
      brain showed tissue injuries with many PrP-plaques in the cerebral cortices, and
      the pyramidal tract showed myelin loss/pallor. In Case 3, the brain was least
      degenerated with a number of PrP-plaques; however, the pyramidal tract remained
      intact. In addition, p-tau was deposited in all cases, where p-tau was present in
      or around PrP-plaques. By double-labeling immunohistochemistry, the
      colocalization of p-tau with PrP-plaques was confirmed. Moreover in Case 2, Abeta
      was deposited in the cerebral cortices. Interestingly, not only p-tau but also
      Abeta was colocalized with PrP-plaques. In all cases, both three repeat tau and
      four repeat tau were associated with PrP-plaques. CONCLUSIONS: The
      clinicopathological diversity of GSS105, which is possible even in the same
      family, was ascertained. Not only p-tau but also Abeta could be induced by PrP
      ("secondary degeneration"), facilitating the kaleidoscopic symptoms of GSS.

PMID- 30240141
TI  - Why does vitreoretinal traction create macular oedema?

PMID- 30240144
TI  - Morphophysiological and Phytochemical Variability in Some Wild Populations of
      Ducrosia anethifolia from Iran.
AB  - In order to determine the morphophysiological and phytochemical properties of
      various Ducrosia anethifolia populations, the plant samples were collected from
      20 locations in native regions. Current study indicated significant differences
      in the morphophysiological and phytochemical characteristics of D. anethifolia
      populations collected from 20 locations in Sistan and Baluchestan Province, Iran.
      The highest value of plant height and the number of lateral stems, node per
      plant, umbellate per umbel, seeds per umbellate and the roots fresh and dry
      weight were related to the location with relatively high rainfall (130-161 mm)
      and low altitude (up to 1165 m) compared with others. Based on the essential oil
      components, D. anethifolia populations were divided into five different
      chemotypes. Chemotypes I, II and III were characterized by high amounts of methyl
      chavicol, chrysanthenyl acetate and decanal, respectively. Moreover, the
      populations with high amounts of decanal, anethole and dodecanal were placed in
      chemotype IV. Chemotype V was attributed to the Naserabad population with 1
      decanol as the major compound.

PMID- 30240143
TI  - Catalytic Transfer Hydrogenation of Biomass-Derived Substrates to Value-Added
      Chemicals on Dual Functional Catalysts: Opportunities and Challenges.
AB  - Aqueous phase hydrodeoxygenation (APH) of bio-derived feedstocks into useful
      chemical building blocks is one the most important processes for biomass
      conversion. But several technological challenges, such as elevated reaction
      temperature (220-280 oC), high H2 pressure (4-10 MPa), uncontrollable side
      reactions and intensive capital investment have bottlenecked further development
      of existing APH processes. Catalytic transfer hydrogenation (CTH) under much
      milder conditions using non-fossil based H2 have attracted extensive interests
      due to several advantageous features, including (i) high atom efficiency (~100%),
      (ii) low energy intensity, and (iii) green H2 obtained from renewable sources.
      Typically, CTH can be categorized as (a) internal H2 transfer (sacrificing small
      amounts of feedstocks for H2 generation) and (b) external H2 transfer from H2
      donors (e.g., alcohols, formic acid). Although recent decade has witnessed a few
      successful applications of conventional APH technologies, CTH is still relatively
      new for biomass conversion. Very limited attempts have been made in both academia
      and industry. Understanding the fundamentals on precise control of catalyst
      structures is key for tunable dual functionality, combining simultaneous H2
      generation and hydrogenation. Therefore, this review is focused on rational
      design of dually functionalized catalysts synchronizing H2 generation and
      hydrogenation of bio-feedstocks into value-added chemicals via CTH technologies.
      Most recent studies, published from 2015-2018, on transformation of selected
      model compounds including glycerol, xylitol, sorbitol, levulinic acid,
      hydroxylmethylfurfural, furfural, cresol, phenol and guaiacol will be critically
      reviewed in this article. The relationship between nanostructures of
      heterogeneous catalysts and catalytic activity and selectivity for C-O, C-H, C-C
      and O-H bond cleavage, will be particularly discussed to provide insights into
      future design for atom economical conversion of biomass to fuels and chemicals.

PMID- 30240145
TI  - Introducing ribosomal tandem repeat barcoding for fungi.
AB  - Sequence comparison and analysis of the various ribosomal genetic markers are the
      dominant molecular methods for identification and description of fungi. However,
      new environmental fungal lineages known only from DNA data reveal significant
      gaps in our sampling of the fungal kingdom in terms of both taxonomy and marker
      coverage in the reference sequence databases. To facilitate the integration of
      reference data from all of the ribosomal markers, we present three sets of
      general primers that allow for amplification of the complete ribosomal operon
      from the ribosomal tandem repeats. The primers cover all ribosomal markers: ETS,
      SSU, ITS1, 5.8S, ITS2, LSU and IGS. We coupled these primers successfully with
      third-generation sequencing (PacBio and Nanopore sequencing) to showcase our
      approach on authentic fungal herbarium specimens (Basidiomycota), aquatic
      chytrids (Chytridiomycota) and a poorly understood lineage of early diverging
      fungi (Nephridiophagidae). In particular, we were able to generate high-quality
      reference data with Nanopore sequencing in a high-throughput manner, showing that
      the generation of reference data can be achieved on a regular desktop computer
      without the involvement of any large-scale sequencing facility. The quality of
      the Nanopore generated sequences was 99.85%, which is comparable with the 99.78%
      accuracy described for Sanger sequencing. With this work, we hope to stimulate
      the generation of a new comprehensive standard of ribosomal reference data with
      the ultimate aim to close the huge gaps in our reference datasets.

PMID- 30240147
TI  - Idea and innovation: Secure fixation between dermis and periosteum using
      perforator flap to prevent recurrence of pilonidal sinus disease.
AB  - In the past decades, numerous surgical techniques and conservative treatments for
      pilonidal sinus disease (PSD) had been discussed and published. There is still no
      consensus yet of the best techniques because of high recurrence rates and
      prolonged wound healing. In the case of complicated discharging sinus or
      recurrent PSD resistant to treatment with antibiotics, we recommend radical
      excision followed by a regional flap, which can obliterate the dead space with
      well-vascularised tissue. In this article, we presented the technique of snug
      suture fixation between the dermis and periosteum using a superior gluteal artery
      perforator (SGAP) flap. The study demonstrates a few key concepts on the
      prevention of PSD recurrence, an off-midline, well-perfused flap that allows
      flattened natal cleft and obliteration of gluteal cleft and eventually showed
      good aesthetic results. We aim to demonstrate a reliable surgical technique for
      wound closure of recurrent pilonidal sinus after radical excision followed by
      reconstruction with an SGAP flap. The history, surgery, and images are described,
      and the literature is reviewed. The pitfalls of disease recurrence will be
      discussed in this literature. Keys to successful treatment will be elaborated. An
      18-year-old female with recurrent pilonidal sinus disease over right medial
      gluteal region presented with sacral pain and infection. She developed
      progressive swelling and burst of abscess from several sinus tracts and did not
      respond to the treatment with antibiotics alone. After radical excision of the
      entire pilonidal sinus and adjacent fibrotic tissue, a deep and large defect was
      measured. A superior gluteal perforator flap was designed based on three
      perforators from the superior gluteal artery. A medial 3 cm of the SGAP flap was
      de-epithelised to provide soft tissue bulk to obliterate the deep cavity. Strong
      sutures were applied to secure the flap to the periosteum. There was no
      recurrence at 3 years of follow up. The patient stood the operation well and had
      prompt recovery.

PMID- 30240146
TI  - Evaluation of the prognostic value of CD3, CD8, and FOXP3 mRNA expression in
      early-stage breast cancer patients treated with anthracycline-based adjuvant
      chemotherapy.
AB  - BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have been shown to be of
      prognostic value in several cancer types. In early breast cancer, TILs have a
      prognostic utility, as well, especially in HER2-positive and triple-negative
      breast cancer. TILs presence is broadly associated with improved survival;
      however, there is controversy regarding TILs subpopulations. PATIENTS AND
      METHODS: Early-stage breast cancer patients treated with anthracycline-based
      chemotherapy within two randomized trials were included in the study. We
      evaluated, by qRT-PCR, 826 tumor tissue samples for mRNA expression of CD3, CD8,
      and FOXP3 for potential prognostic significance in terms of disease-free survival
      (DFS) and overall survival (OS). RESULTS: After a median follow-up of 133.0
      months, 255 patients (30.9%) had died and 314 (38.0%) had disease progression. In
      the univariate analysis, high CD3 and CD8 mRNA expression was found to be of
      favorable prognostic value for DFS (P = 0.007 and P = 0.016, respectively). In
      multivariate analyses, the association of high CD8 mRNA expression with increased
      DFS was retained (HR = 0.77, 95% CI 0.60-0.998, Wald's P = 0.048), whereas that
      of high CD3 mRNA expression was of marginal statistical significance (HR = 0.77,
      95% CI 0.59-1.01, P = 0.059). Moreover, a significant interaction was observed
      between HER2 status and CD3 mRNA expression with respect to DFS (interaction P =
      0.032). In the HER2-positive subgroup, the hazard ratio associated with high CD3
      mRNA expression was of greater magnitude (HR = 0.48, 95% CI 0.30-0.76, P = 0.002)
      compared with the hazard ratio presented above, for the entire cohort. No
      significant findings were observed for FOXP3 in terms of DFS, while none of the
      studied markers were of prognostic value for OS. CONCLUSIONS: High CD3 and CD8
      mRNA expression in early-stage breast cancer patients is of prognostic value for
      decreased risk of relapse and, in the future, could potentially be of importance
      in deciding the most appropriate therapeutic strategy in light of the recent
      immune-related treatment developments.

PMID- 30240149
TI  - BODIES R US: Ethical Views on the Commercialization of the Dead in Medical
      Education and Research.
AB  - With the ongoing and expanding use of willed bodies in medical education and
      research, there has been a concomitant rise in the need for willed bodies and an
      increase in the means of supplying these bodies. A relatively recent development
      to enlarge this supply has been the growth of for-profit willed body companies
      ("body brokers") in the United States. These companies advertise for donors,
      cover all cremation and other fees for the donor, distribute the bodies or body
      parts nationally and internationally, and charge their users for access to the
      body or body parts. In doing so, they generate substantial profits. This review
      examines the historical development of willed body programs, the legal and
      economic aspects of willed body programs, and then provides an ethical framework
      for the use of willed bodies. The ethical principles described include detailed
      informed consent from the donors, comprehensive and transparent information about
      the process from the body donation organizations, and societal input on the
      proper and legal handling of willed bodies. Based on the ethical principles
      outlined, it is recommended that there be no commercialization or commodification
      of willed bodies, and that programs that use willed bodies should not generate
      profit.

PMID- 30240148
TI  - Astrocytes and radial glia-like cells, but not neurons, display a nonapoptotic
      increase in caspase-3 expression following exercise.
AB  - BACKGROUND: Exercise induces plasticity in the hippocampus, which includes
      increases in neurogenesis, the proliferation of new neurons, and angiogenesis,
      the sprouting of new capillaries from preexisting blood vessels. Following
      exercise, astrocytes also undergo morphological changes that parallel the events
      occurring in the neurovascular system. Interestingly, there have also been
      reports of apoptosis in the hippocampus following aerobic exercise. This
      experiment aimed to identify which population of hippocampal cells undergoes
      apoptosis after an acute bout of exercise. METHODS: Cleaved caspase-3, a terminal
      protein in the apoptotic cascade, was initially used to identify apoptotic cells
      in the hippocampus after rats completed an acute bout of exercise. Next, the
      proportion of immature neurons, adult neurons, astrocytes, or radial glia-like
      cells expressing cleaved caspase-3 was quantified. TUNEL staining was completed
      as a second measure of apoptosis. RESULTS: Following exercise, cleaved caspase-3
      expression was increased in the CA1 and DG regions of the hippocampus. Cleaved
      caspase-3 was not highly expressed in neuronal populations, and expression was
      not increased in these cells postexercise. Instead, cleaved caspase-3 was
      predominantly expressed in astrocytes. Following exercise, there was an increased
      number of cleaved caspase-3 positive astrocytes in DG and CA1, and cleaved
      caspase-3 positive radial glia-like cells located in the subgranular zone. To
      determine whether cleaved caspase-3 expression in these glial cells was
      associated with apoptosis, a TUNEL assay was completed. TUNEL staining was
      negligible in all groups and did not mirror the pattern of caspase-3 labeling.
      CONCLUSIONS: Cleaved caspase-3 expression was detected largely in non-neuronal
      cell populations, and the pattern of cleaved caspase-3 expression did not match
      that of TUNEL. This suggests that after exercise, cleaved caspase-3 expression
      may serve a nonapoptotic role in these hippocampal astrocytes and radial glia
      like cells. It will be important to identify the function of exercise-induced
      cleaved caspase-3 expression in the future experiments.

PMID- 30240150
TI  - Multiparity affects conduction properties of pelvic floor nerves in rabbits.
AB  - INTRODUCTION: Women often develop pelvic floor dysfunction due to damage to the
      pelvic musculature during childbirth; however, the effect on pelvic floor nerves
      function is less understood. This study used adult rabbits to evaluate the
      electrophysiological and histological characteristics of the bulbospongiosus
      (Bsn) and pubococcygeus nerves (Pcn) in multiparity. METHODS: Compound nerve
      action potentials (CNAP) were compared between age-matched nulliparous and
      multiparous animals and associated to the histological characteristics of
      myelinated axons from the Bsn and Pcn nerves. The extensor digitorum longus nerve
      (EDLn) was used as negative control. Data were analyzed with unpaired two-tailed
      Student's t test or Mann-Whitney U test to determine significant differences
      between groups. RESULTS: The onset and peak latencies, duration, and conduction
      velocity of the motor fibers in these pelvic nerves were not significantly
      different between nulliparous and multiparous animals. However, the peak-to-peak
      amplitude and area of the CNAP in both Bsn and Pcn were reduced in multiparous
      rabbits. Histology showed a higher percentage of axons with myelin
      disorganization caused by multiparity in these pelvic nerves. Together, the data
      indicate a reduction in the number of functional pelvic axons due to multiparity.
      As expected, no effect of parity was observed in the EDLn controls. CONCLUSIONS:
      Present findings demonstrated that multiparity affects myelination and
      consequently conduction properties in the small pelvic floor nerves.

PMID- 30240151
TI  - Relative abundance of nasal microbiota in chronic rhinosinusitis by structured
      histopathology.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease process with
      several different phenotypes. Recent data has shown that CRS phenotypes maintain
      distinct nasal microbiota that may predict surgical outcomes. Nasal microbiota
      and structured histopathologic reporting have the potential to further
      differentiate subtypes and provide additional insight into the pathophysiology of
      CRS. METHODS: Sinus swabs collected during functional endoscopic sinus surgery
      (FESS) were studied by polymerase chain reaction analysis of 16S ribosomal RNA. A
      structured histopathology report of 13 variables was utilized to analyze sinus
      tissue removed during FESS. Histopathology variables and relative abundance of
      nasal microbiota were compared among CRS patients. RESULTS: A total of 51 CRS
      patients who underwent FESS were included. Relative abundance of the Firmicutes
      phylum in nasal microbiota of CRS patients was associated with presence of
      neutrophilic infiltrate (27.47 +/- 44.75 vs 9.21 +/- 11.84, p < 0.029), presence
      of mucosal ulceration (47.67 +/- 45.52 vs 13.27 +/- 26.48, p < 0.041), presence
      of squamous metaplasia (5562.70 +/- 2715.66 vs 3563.73 +/- 2580.84, p < 0.035),
      and absence of Charcot-Leyden crystals (5423.00 +/- 3320.57 vs 679.94 +/-
      1653.66, p < 0.001). Relative abundance of the Bacteroidetes phylum in nasal
      microbiota of CRS patients was associated with increased severity of inflammatory
      degree (p < 0.004) and presence of mucosal ulceration (p < 0.004). CONCLUSION:
      Distinct histopathologic features of CRS are associated with relative abundance
      of nasal microbiota phyla, specifically Firmicutes and Bacteroidetes. These
      findings contribute to the growing body of literature on microbiota in sinonasal
      disease and may have important implications for understanding pathophysiologic
      mechanisms of CRS subtypes and disease management.

PMID- 30240152
TI  - Protein Nanotherapeutics as an Emerging Modality for Cancer Therapy.
AB  - Protein drugs are a unique and versatile class of biotherapeutics that have not
      only high biological activity but also superb specificity. This rapidly evolving
      biotechnology has rendered it possible to produce various proteins in a large
      scale and reproducible way. Many proteins have demonstrated striking anticancer
      activities and have emerged as advanced alternatives to cytotoxic
      chemotherapeutic agents for cancer therapy. The clinical translation of
      anticancer proteins with intracellular targets is, nevertheless, severely
      hindered by their fast degradation in vivo, poor cell penetration, and
      inefficient intracellular transportation. The past few years have witnessed
      tremendous effort and progress in developing polymeric protein delivery
      nanosystems, ranging from nanoparticles, nanocapsules, nanogels, micelles, to
      polymersomes, for the treatment of different tumors such as lung tumors, breast
      tumors, ovarian cancers, and glioblastoma. These proof-of-concept studies point
      out that protein nanotherapeutics, with rationally designed nanovehicles, are
      able to overcome the extracellular barriers, cell membrane barriers, and
      intracellular barriers, and systemically deliver proteins into targeted cancer
      cells, resulting in effective cancer protein therapy. Protein nanotherapeutics
      appear to be a novel modality for safe and efficient cancer treatment.

PMID- 30240153
TI  - Studying Osteoarthritis Pathogenesis in Mice.
AB  - With the increasing availability and complexity of mouse models of disease,
      either spontaneous or induced, there is a concomitant increase in their use in
      the analysis of pathogenesis. Among such diseases is osteoarthritis, a
      debilitating disease with few treatment options. While advances in our
      understanding of the pathogenesis of osteoarthritis has advanced through clinical
      investigations and genome-wide association studies, there is still a large gap in
      our knowledge, hindering advances in therapy. Patient samples are available ex
      vivo, but these are generally in the very late stages of disease. However, with
      mice, we are able to induce disease at a defined time and track the progression
      in vivo and ex vivo, from inception to end stage, to delineate the processes
      involved in disease development. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30240154
TI  - Lomerizine, trimetazidine and bis-(4-fluorophenyl)-methylpiperazine in human
      urine after oral administration of lomerizine dihydrochloride: analysis by liquid
      chromatography-high resolution-tandem mass spectrometry.
AB  - In sports drugs testing, the differentiation between the abuse of the prohibited
      substance trimetazidine and that of the permitted drug lomerizine is required
      because trimetazidine is one of the metabolites of lomerizine. Therefore, it is
      important to identify a lomerizine-specific metabolite in urine that allows
      making the distinction. In this study, a simple dilute-and-shoot method employing
      liquid chromatography-high resolution-tandem mass spectrometry for the
      quantification of trimetazidine, lomerizine and the specific metabolite bis-(4
      fluorophenyl)-methylpiperazine (M6) in urine was developed. An oral dose of 15 mg
      was administered to 10 male volunteers, after which urine samples collected
      during the following 276 hours were analyzed using the developed method, allowing
      for examination of the target analytes' excretion profile. The limit of detection
      of all target analytes was <0.02 ng/mL. In all volunteers, the metabolite M6 was
      detected up to 276 hours after administration. After more than 12 hours, all
      volunteers were found to have higher concentrations of the metabolite M6 than of
      trimetazidine. The concentrations of trimetazidine, lomerizine, M6, and the
      M6/trimetazidine ratio in the final sample collected after 276 hours were 0.2-0.9
      ng/mL, <0.05-0.1 ng/mL, 14.1-38.3 ng/mL, and 28.8-122.9, respectively. The
      urinary excretion of trimetazidine, unchanged lomerizine, and the metabolite M6
      within the first 276 hours was 0.64%, 0.006%, and 6.1%, respectively.
      Consequently, the absence of the metabolite M6 in doping control urine samples
      corroborates the conclusion that lomerizine is unlikely to be the source of
      trimetazidine. The results confirm that the M6 metabolite is the longest-lasting
      urinary metabolite of lomerizine currently known.

PMID- 30240156
TI  - Editorial of Issue 2 in 2016.

PMID- 30240155
TI  - A Large-Sized Reduced Graphene Oxide with Low Charge-Transfer Resistance as a
      High-Performance Electrode for a Nonflammable High-Temperature Stable Ionic
      Liquid-Based Supercapacitor.
AB  - Large-sized reduced graphene oxide prepared was prepared by combined microwave
      intermittent heating and an extraction process (e.g., 900 W for 10 min (MRG-900
      10)) with a lateral size of several micrometers and a thickness of 4-6 monosheets
      . The MRG-900-10 has a high C/O molar ratio (5.89) and a sp2 C content of 69.0 %,
      which leads to a fast electronic transmission in the sample. In addition, MRG-900
      10 possesses a large specific surface area of 568.2 m2  g-1 , which increases the
      contact surface area between the active material and the electrolyte, thus
      enhancing the electron and ion transport in the interfaces when used as the
      electrode material in supercapacitors. MRG-900-10 possesses a low charge-transfer
      resistance (~0.36 Omega). Used as the electrode material for a supercapacitor in
      6 m KOH aqueous electrolyte, MRG-900-10 produces a high specific capacity of
      327.6 F g-1 at the current density of 0.5 A g-1 . A specific capacity of 248.3 F
      g-1 was obtained at a high current density of 100 A g-1 , which indicated its
      high-rate ability. The initial capacity of 92 % can be maintained after 40 000
      cycles at 5 A g-1 , which indicated its high cycling stability. As for the MRG
      900-10 symmetric supercapacitors, the energy densities of 11.0 and 36.2 Wh kg-1
      were obtained in 6 m KOH aqueous and 1 m tetraethylammonium tetrafluoroborate
      ([TEA]BF4 )/acetonitrile (ACN) electrolytes, respectively. Importantly, a high
      energy density of 68.6 Wh kg-1 was achieved in the nonflammable ionic liquid 1
      ethyl-3-methylimidazolium bis(trifluoromethane)sulfonimide ([EMIM][TFSI])/ACN (80
      vol % [EMIM][TFSI]), and the supercapacitor was effective from room temperature
      to 100  degrees C.

PMID- 30240158
TI  - Spotlights on our sister journals: ChemMedChem 21/2016.

PMID- 30240159
TI  - Issue Highlights-September 2018 (94B5).

PMID- 30240157
TI  - Biomineralization-Inspired Material Design for Bone Regeneration.
AB  - Synthetic substitutes of bone grafts, such as calcium phosphate-based ceramics,
      have shown some good clinical successes in the regeneration of large bone defects
      and are currently extensively used. In the past decade, the field of
      biomineralization has delivered important new fundamental knowledge and
      techniques to better understand this fascinating phenomenon. This knowledge is
      also applied in the field of biomaterials, with the aim of bringing the
      composition and structure, and hence the performance, of synthetic bone graft
      substitutes even closer to those of the extracellular matrix of bone. The purpose
      of this progress report is to critically review advances in mimicking the
      extracellular matrix of bone as a strategy for development of new materials for
      bone regeneration. Lab-made biomimicking or bioinspired materials are discussed
      against the background of the natural extracellular matrix, starting from basic
      organic and inorganic components, and progressing into the building block of
      bone, the mineralized collagen fibril, and finally larger, 2D and 3D constructs.
      Moreover, bioactivity studies on state-of-the-art biomimicking materials are
      discussed. By addressing these different topics, an overview is given of how far
      the field has advanced toward a true bone-mimicking material, and some
      suggestions are offered for bridging current knowledge and technical gaps.

PMID- 30240160
TI  - Inter-laboratory validation of a harmonized PNH flow cytometry assay.
AB  - BACKGROUND: A network comprising 11 laboratories aimed to consolidate PNH testing
      by developing and validating an assay guided by previous guidelines and studies.
      Network analyses of >20 native samples yielded key findings that were used to
      create and reshape the final protocol. METHODS: Twenty-seven native samples were
      distributed to all participating laboratories for blind testing, local analysis,
      and subsequent re-analysis by a central laboratory. Inter-laboratory clone size
      precision (coefficient of variation [CV]) was monitored for each sample, and the
      findings used to refine the test protocol. Linearity and precision tests were
      performed, assay limits of blank and detection were calculated, and limits of
      quantification were determined. RESULTS: When using the final protocol,
      enumeration of cells with a PNH phenotype by all participating laboratories was
      comparable, with no clinically significant discrepancies or false-positive or
      false-negative results reported. Of note, the biological characteristics of the
      sample affected precision. For example, CVs were higher when PNH and normal cells
      showed contiguous expression of GPI-linked antigens. A red cell gating strategy
      that eliminated non-specific type II PNH phenotypic events was devised, enabling
      reliable reporting of events in the type II red cell gate. The final protocol
      provided an assay with a Limit of Quantification of 0.01% for neutrophils and red
      cells, and 0.1% for monocytes. CONCLUSIONS: We describe a robust network
      validated PNH assay that may aid other laboratories to set up and validate high
      resolution PNH analysis. (c) 2018 International Clinical Cytometry Society.

PMID- 30240161
TI  - Flow cytometric assays for identity, safety and potency of cellular therapies.
AB  - Cellular therapeutics are a fast-growing, highly innovative area of medicine.
      This field encompasses well-established immune therapies for infection and
      cancer, as well as newer cell therapies aimed at regenerating diseased tissue.
      Flow cytometry is arguably the most important tool in the development of advanced
      cellular therapeutics and plays a role in many aspects of manufacturing. Quality
      control of raw materials, assessing rates of cellular growth during complex in
      vitro culture processes, differentiation status, as well as final product
      characterization, viability, and product stability are all essential data to be
      collected and documented. This requires robust and validated flow cytometric
      analysis. In this review, we discuss flow cytometer set up; design and use of
      assays to maintain quality control in cell processing, and the building of a
      robust set of release criteria. The use of flow cytometric assays as surrogates
      of functional assays to allow comparison and release of cellular products for
      clinical use are reviewed with reference to monocyte-derived and T cell products.

PMID- 30240163
TI  - Should we be routinely testing for circulating clonal plasma cells in patients
      with multiple myeloma?

PMID- 30240162
TI  - Accurate quantification of fourteen normal bone marrow cell subsets in infants to
      the elderly by flow cytometry.
AB  - BACKGROUND: Studies of normal bone marrow (BM) cell composition by flow cytometry
      are scarce. Presently, we aimed to quantify 14 cell subsets from infants to
      elderly patients. METHODS: Cell subsets in BM samples from 180 individuals
      without morphologically abnormal leukocytes were analyzed using a single
      combination of eight antibodies: CD3/CD10/CD38/CD19/CD36/CD16/CD34/CD45. RESULTS:
      By comparison with the Holdrinet score, we first validated the immature
      granulocyte/neutrophil (IGRA/N) ratio as a readily obtainable criterion of BM
      sample purity in 145 cases. Then, the 115 highly pure samples were selected
      (IGRA/N >= 1.2) and analyzed according to age group. CD34+ myeloblasts became
      progressively more infrequent with age: median 1.4% in infancy to 0.5% in the
      elderly. Neutrophils increased: 10.7% to 22.8%; all other myeloid subsets, IGRA,
      eosinophils, basophils and monocytes remained stable: respectively 40.3% to
      46.7%, 2.0% to 2.8%, 0.2% to 0.3%, and 4.4% to 5.0% throughout life.
      Erythroblasts were lower in children (8.4% to 10.3%) than in adults (12.5% to
      15.1%). For lymphoid cells, hematogones and transitional B-cells decreased: 15.5%
      to 0.6% and 3.6% to 0.1%, respectively; mature lymphocytes remained stable: B
      cells: 1.4% to 2.8%, T-cells: 5.8% to 8.7%, and NK-cells: 0.7% to 1.4%. Plasma
      cells varied slightly: 0.1% to 0.5%. Differences of about 40% were seen in
      moderately pure (IGRA/N: 0.5 to 1.2) BM samples. CONCLUSION: We thus provide the
      first values for 14 myeloid and lymphoid subsets characterizing BM cell
      composition in 5 age ranges. They should provide important information when
      screening patients for hematological disorders or abnormal bone marrow
      development. (c) 2018 International Clinical Cytometry Society.

PMID- 30240166
TI  - Farewell Singh.

PMID- 30240165
TI  - Bi2 S3 -Tween 20 Nanodots Loading PI3K Inhibitor, LY294002, for Mild Photothermal
      Therapy of LoVo Cells In Vitro and In Vivo.
AB  - Although various types of photothermal agents are developed for photothermal
      cancer therapy, relatively few photothermal agents exhibit high tumor inhibition
      rate under relatively mild conditions. Herein, a multifunctional Bi2 S3 -Tween 20
      nanoplatform loaded with PI3K inhibitor LY294002 is designed as a novel
      photothermal agent for inhibitor and photothermal synergistic therapy of tumors
      under mild photothermal therapy conditions. The LY294002 of PI3K inhibitor, after
      being loaded by Bi2 S3 -Tween 20 nanodots, exhibits greatly increased drug
      utilization and reduced side effects on normal tissues. In vivo, Bi2 S3 -Tween
      20@LY294002 upon near-infrared 808 nm laser irradiation shows potent antitumor
      activity under relatively mild conditions (power density: 0.6 W cm-2 ). Moreover,
      the mechanism studies also demonstrate that Bi2 S3 -Tween 20@LY294002 potently
      kills LoVo cancer cells under low-power near-infrared light irradiation, by
      downregulating the expression of heat shock protein 70 (HSP70) so as to increase
      the sensitivity of tumor cell hyperthermia and activating BAX/BAK-regulated
      mitochondrial apoptosis pathway. The results demonstrate that the newly
      synthesized multifunctional nanoplatform paves a new avenue for accurate therapy
      of photothermal-resistant cancer.

PMID- 30240164
TI  - Functional outcome and survival following spontaneous intracerebral hemorrhage: A
      retrospective population-based study.
AB  - BACKGROUND: Accurate and reliable clinical and radiological predictors of
      intracerebral hemorrhage (ICH) outcomes are needed to optimize treatment of ICH.
      The aim of this study was to investigate functional outcome and identify
      predictors of severe disability or death following ICH. MATERIALS AND METHODS:
      Retrospective population-based study of spontaneous ICH. Clinical and
      radiological data were obtained from electronic medical records, and functional
      outcome estimated using the modified Rankin Scale (mRS) before ICH and at 3 and
      12 months after ICH. RESULTS: Four hundred and fifty-two patients were included
      (mean age 74.8 years, 45.6% females). Proportion of fatal outcome at 1 week was
      22.1%, at 3 months 39.2%, and at 12 months 44.9%. Median mRS score before the ICH
      was 1 (interquartile range [IQR] 2); for survivors at 3 months, it was 5 (IQR 3);
      and at 12 months, it was 3 (IQR 2). Independent predictors of severe disability
      (mRS of 5) or death (mRS of 6) were use of oral antithrombotic drugs (OR 2.2, 95%
      CI 1.3-3.8, p = 0.04), mRS score before the ICH (OR 1.8, 95% CI 1.4-2.2, p <
      0.001), Glasgow Coma Scale (GCS) on admission (OR 8.3, 95% CI 3.5-19.7, p <
      0.001), hematoma volume >60 ml (OR 4.5, 05% CI 2.0-10.2, p < 0.001), and
      intraventricular hematoma extension (OR 1.8, 95% CI 0.8-4.2, p < 0.001).
      CONCLUSION: Intracerebral hemorrhage is associated with high mortality, and more
      than one third of survivors end up with severe disability or death 3 months
      later. Predictors of severe disability or death were use of oral antithrombotic
      drugs, functional disability prior to ICH, low GCS on admission, larger hematoma
      volume, and intraventricular hematoma extension.

PMID- 30240167
TI  - Prof. Gursharan Singh Chhatwal: an exceptional Punjabi Scientist.

PMID- 30240168
TI  - Singh Chhatwal: A magical scholar and exceptional Streptococcus researcher.

PMID- 30240169
TI  - Tribute to professor Gursharan Singh Chhatwal.

PMID- 30240170
TI  - Singh Chhatwal, our friend.

PMID- 30240171
TI  - In tribute to Singh Chhatwal.

PMID- 30240173
TI  - Singh's love affair with Australia.

PMID- 30240172
TI  - Habitat partitioning of marine benthic denitrifier communities in response to
      oxygen availability.

PMID- 30240175
TI  - Upcoming events of interest.

PMID- 30240174
TI  - Response from the authors.

PMID- 30240177
TI  - Public health approaches to the prevention of oral diseases and promotion of oral
      health in Nigeria.
AB  - Oral health is an important component of general health and a determinant factor
      for quality of life. Though oral diseases are largely preventable, many people
      across the globe still suffer from pain and discomfort associated with oral
      diseases. The attainment of optimum oral health is impeded by a number of
      obstacles which include the cost and affordability of treatment, poor access due
      to workforce shortages and inequitable distribution of the dental workforce and
      low oral health literacy amongst others. The provision of oral health services is
      oriented towards curative care. There appears to be no coordinated national
      strategy for preventive dental care in Nigeria.Effective public health strategies
      are required to prevent oral diseases and promote oral health across the
      population. Generally, strategies to prevent oral diseases will be most effective
      when priority is given to the multi-sectoral approach rather than a single-sector
      approach, population-based interventions rather than those aimed at high-risk
      individuals, and primary rather than secondary prevention. The aim of this paper
      was to highlight some of the oral diseases in Nigeria and discuss public health
      approaches to promote oral health and prevent the diseases.

PMID- 30240176
TI  - Association of neurofascin IgG4 and atypical chronic inflammatory demyelinating
      polyneuropathy: A systematic review and meta-analysis.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is
      the most commonly observed phenotype among chronic acquired demyelinating
      polyneuropathies and is clinically variable. The aim of this meta-analysis was to
      evaluate the diagnostic value and characteristics of CIDP targeting neurofascin
      155 (NF155). METHODS: A systematic literature search was performed on March 2018,
      and two reviewers independently extracted data and assessed the risk of bias on
      MEDLINE, EMBASE, the Web of Science, and the Cochrane Library to identify
      relevant articles. RESULTS: Ten articles for the NF155 protein test with 1,161
      patients and 1,636 controls were identified. The results showed that the pooled
      sensitivity was 0.09 (95% CI: 0.06-015), and specificity was 1.00 (95% CI: 0.98
      1.00) of the NF155 for CIDP. The meta-analysis revealed that the sensory ataxic
      occurrence rate (OR: 10.79, 95% CI: 5.24-22.22) and tremor occurrence rate (OR:
      6.71, 95% CI: 3.37-13.39) were higher among patients positive for NF155 compared
      with NF155-negative CIDP patients. However, the rate of good treatment response
      to intravenous immunoglobulin (IVIg) (OR: 0.09, 95% CI: 0.02-0.42) was lower in
      NF155-positive CIDP patients. CONCLUSIONS: NF155 is a specific protein marker for
      CIDP, but its diagnostic value has been questioned due to low sensitivity.
      However, as an antibody against paranodal antigens, NF155 seems more valuable in
      defining clinical subsets of CIDP.

PMID- 30240179
TI  - Sociodemographic determinants of usage of removable partial denture in a tertiary
      hospital: A retrospective study.
AB  - Objective: To determine the influence of sociodemographic characteristics on
      pattern of removable partial denture use in a tertiary institution over a one
      year period. Methods: This was a retrospective study using records of partially
      dentate patients seeking replacement for their missing teeth within one-year
      duration. Information retrieved from the patients' records included demographic
      characteristics such as gender, age, marital status, occupation, arch type,
      number and reasons for missing teeth and type of removable partial denture.
      Statistical analysis was performed using statistical package for social science
      (SPSS) version 17 (Chicago, IL.). The analysis was done using frequency
      distribution, cross tabulations, t test and test of significance with chi square.
      P<0.05 was considered statistically significant. Results: A total of 98 patients
      were seen over the study period with a male/female ratio of 1:1.45. The patients'
      age ranged from 20 to 89 years with a mean age of 47.19 +/- 18.37. The number of
      teeth replaced ranged from 1 to 17 with a mean of 3.13 +/- 3.30 teeth. The mean
      number of missing teeth was significantly higher among patients aged 50 years and
      above (p = 0.002). Majority (69.4%) of the patients were married and 59.2% were
      working class (skilled and unskilled). The Kennedy's Class III saddle was the
      most prevalent in the maxilla while Class IV was most prevalent in the mandible;
      a difference that was statistically significant.Conclusion: Socioeconomic status,
      age and gender influenced the use of removable partial denture.

PMID- 30240178
TI  - [Evaluation of periodontal health of Congolese in consultation in dental services
      of Kinshasa City].
AB  - Context: Periodontal diseases are multifactorial infectious pathologies. They
      affect tissues of support of the tooth and so end in dental losses. No sector of
      society is spared. Objective: To estimate the state of periodontal health of the
      patients admitted in consultation in the dental services of the city of Kinshasa.
      Material and Methods: It is a descriptive and transverse study. It was led on
      patients admitted in consultations in three dental services of the city of
      Kinshasa during the period going from January to August, 2015. The study included
      patients of 12 years old and more who consulted in one of the selected dental
      service. The selected patients supplied sociodemographic information in
      particular zone of residence, gender, level of education and social level. Dutch
      Periodontal Screening Index (DPSI) was used to estimate the periodontal state of
      every patient. Results: On a total of 642 patients 374 were females and 268 were
      males. The mean age was of 38.12 years +/- 16,303. The patients of upper or more
      university level and those who had no employment represented successively 58.3%
      and 35.5%. Dental pain was the main motive for consultation. Majority of the
      patients had a DPSI around 3, that is 49.1%. 99.9% of the patients presented
      gingivitis whereas those 64% who suffered from periodontitis were subject to
      specialized periodontal care. Conclusion: Periodontal disease was present in all
      patients. The majority of the people had consulted dental surgeons only when they
      had pain.

PMID- 30240180
TI  - Natural, polarized light and the choice of composite: a key to success in shade
      matching of direct anterior restorations- Part II.
AB  - With time, natural and polarized light proved their importance and utility in
      dental photography. After studying the physical properties of natural and
      polarized light, in the first part of this article, to understand their
      correlation with dental materials and natural teeth and how to use them in the
      best combination, this second part will illustrate the importance of a polarized
      image in color matching, how to manipulate it and how to apply it in clinical
      cases.

PMID- 30240181
TI  - Morphology of the root apex of permanent teeth. A scanning electron microscope
      study in a Moroccan population.
AB  - This study aimed to investigate the root apex morphology in permanent teeth of a
      Moroccan population using scanning electron microscope. Eighty-seven teeth were
      collected from Moroccan patients attending the Oral Surgery Department of the
      faculty of dentistry, Mohammed V University, Rabat, Morocco. The extracted teeth
      were then prepared for scanning electron microscope (SEM) observation at a root
      apex slice thickness of 5 mm.The median distance of the apical foramen from the
      apex was about 0.37 [0-0.62] mm, 0. 60 [0-0.82] mm, 0.71 [0.36-0.94] mm in
      incisors/canines, bi-rooted and multi-rooted teeth respectively, the mean apical
      foramen diameter was 0.30 [0.23-0.34] mm, 0.24 [0.18-0.33] mm, 0.27 [0.19-0.35]
      mm in incisors/canines, bi-rooted and multi-rooted teeth respectively. The apical
      foramen coincided with the apex in 33.5%, 33%, and 30.8% in incisors/canines, bi
      rooted, and multi-rooted teeth. 16.45% of incisors, and 10.1% of the bi-rooted
      teeth with pulp and peri-apical diseases showed apical resorptions.

PMID- 30240182
TI  - [Evaluation of the action " M'T Dents " for 6-year-old schoolchildren on two
      deprived neighborhoods in Marseille, France].
AB  - Background: This study aims to analyze the effects of the national program for
      individual dental prevention "M'T Dents" to 6-years-old children living in the
      neighborhoods of deprived areas Saint-Mauront and Belle de Mai from 2009 to 2012
      (Marseille, France). These children having received an additional collective
      awareness and individual monitoring as part of the experimental program of health
      promotion "La Sante a Saint Mauront - Belle de Mai: on s'y met tous!" led by the
      PACA Regional Health Agency. Materials and Methods: Awareness sessions in oral
      hygiene were led in CP grades of 5 schools and each child was then followed and
      encouraged to resort to dentist. Data on the use of the bucco-dental examination
      (BDE), the use of consecutive care and the oral health status of children were
      collected. Results: Of the three years considered by this study, 56 classes and
      more than 1000 children were involved by this prevention program. The average use
      of BDE was 27.70%. Among children who received the BDE, 44.33% required
      treatment, approximately 26% with 1-3 untreated caries, 12%: 4-6 caries and 6%: 7
      caries or more. Nearly 60% were completely cured, 15% partially and 25% not
      treated within 6 months following the BDE. Care utilization varied by initial
      caries index: the percentage of children fully treated was significantly higher
      for children with 1-3 caries than those with 4-6 caries (p <0.05) and those with
      7 caries or more (p < 0.001) when the BDE. Conclusion: Modes of action that are
      reinforced in this territory seem possible to achieve results comparable to those
      observed in the same age group at the national level for children. More children
      were able to use the dentist and receive consecutive care under this program
      contributes to reducing inequalities in oral health.

PMID- 30240183
TI  - Use of dental floss: opinion of present and future oral health workers.
AB  - Objective: To determine the prevalence of the use of dental floss among all
      cadres of present and future dental health workers, in a Nigerian teaching
      hospital, and their opinion on the use of dental floss in the management of
      periodontal diseases. Methodology: A 30-item questionnaire was used to elicit
      information on respondents' demographics, their opinion about the use of dental
      floss in the management of periodontal diseases and their personal use of dental
      floss. It also elicited information on respondents' practice of recommending
      dental floss to dental patients and how confident they are in their ability to
      properly demonstrate the use of dental floss to the patients. Bivariate analyses
      were used to assess whether the position of the oral health workers, their gender
      and their use of dental floss has a relationship with their knowledge, attitude
      and practices regarding the use dental floss. Results: Only 17.4% of the study
      participants flossed daily. A few of the respondents (29.4%) felt that flossing
      should be done after tooth brushing while majority (51.4%) felt it can be done
      anytime. Majority of the study participants use dental floss but fewer
      participants recommend the use of dental floss to their patients (p = 0.001).
      Among the oral health workers who do not use dental floss, 98.9% knew that dental
      floss removes plaque from the interdental area, 64.3% thought that flossing
      polishes the tooth surface as it removes the dental plaque and debris (p = 0.039)
      and 85.7% reported that flossing massages the interdental areas (p = 0.039).
      Conclusion: It can be concluded that majority of the present and future oral
      health workers studied believe in the effectiveness of the use of dental floss in
      the prevention of periodontal diseases and use dental floss occasionally but the
      oral health workers who recommend the use of dental floss to patients are fewer.

PMID- 30240184
TI  - Shared Platform for Antibiotic Research and Knowledge: A Collaborative Tool to
      SPARK Antibiotic Discovery.
AB  - The discovery of urgently needed antibiotics is hindered by challenges to
      information sharing. To help address this challenge, The Pew Charitable Trusts
      launched SPARK: the Shared Platform for Antibiotic Research and Knowledge. SPARK
      is an online, publicly available, interactive database designed to help
      scientists build on previous research and generate new insights to advance the
      field's understanding of Gram-negative permeability. This Viewpoint details how
      data are selected and integrated into the platform, how scientists can use SPARK
      to share their data, and the ways the scientific community can access and use
      these data to develop hypotheses.

PMID- 30240185
TI  - Vascular Targeting of Radiolabeled Liposomes with Bio-Orthogonally Conjugated
      Ligands: Single Chain Fragments Provide Higher Specificity than Antibodies.
AB  - Liposomes are a proven, versatile, and clinically viable technology platform for
      vascular delivery of drugs and imaging probes. Although targeted liposomes have
      the potential to advance these applications, complex formulations and the need
      for optimal affinity ligands and conjugation strategies challenge their
      translation. Herein, we employed copper-free click chemistry functionalized
      liposomes to target platelet-endothelial cell adhesion molecule (PECAM-1) and
      intracellular adhesion molecule (ICAM-1) by conjugating clickable monoclonal
      antibodies (Ab) or their single chain variable fragments (scFv). For direct,
      quantitative tracing, liposomes were surface chelated with 111In to a >90%
      radiochemical yield and purity. Particle size and distribution, stability, ligand
      surface density, and specific binding to target cells were characterized in
      vitro. Biodistribution of liposomes after IV injection was characterized in mice
      using isotope detection in organs and by noninvasive imaging (single-photon
      emission computed tomography/computed tomography, SPECT/CT). As much as 20-25% of
      injected dose of liposomes carrying PECAM and ICAM ligands, but not control IgG
      accumulated in the pulmonary vasculature. The immunospecificity of pulmonary
      targeting of scFv/liposomes to PECAM-1 and ICAM-1, respectively, was 10-fold and
      2.5-fold higher than of Ab/liposomes. Therefore, the combination of optimal
      ligands, benign conjugation, and labeling yields liposomal formulations that may
      be used for highly effective and specific vascular targeting.

PMID- 30240186
TI  - PTML Combinatorial Model of ChEMBL Compounds Assays for Multiple Types of Cancer.
AB  - Determining the target proteins of new anticancer compounds is a very important
      task in Medicinal Chemistry. In this sense, chemists carry out preclinical assays
      with a high number of combinations of experimental conditions (c j). In fact,
      ChEMBL database contains outcomes of 65 534 different anticancer activity
      preclinical assays for 35 565 different chemical compounds (1.84 assays per
      compound). These assays cover different combinations of c j formed from >70
      different biological activity parameters ( c0), >300 different drug targets (
      c1), >230 cell lines ( c2), and 5 organisms of assay ( c3) or organisms of the
      target ( c4). It include a total of 45 833 assays in leukemia, 6227 assays in
      breast cancer, 2499 assays in ovarian cancer, 3499 in colon cancer, 3159 in lung
      cancer, 2750 in prostate cancer, 601 in melanoma, etc. This is a very complex
      data set with multiple Big Data features. This data is hard to be rationalized by
      researchers to extract useful relationships and predict new compounds. In this
      context, we propose to combine perturbation theory (PT) ideas and machine
      learning (ML) modeling to solve this combinatorial-like problem. In this work, we
      report a PTML (PT + ML) model for ChEMBL data set of preclinical assays of
      anticancer compounds. This is a simple linear model with only three variables.
      The model presented values of area under receiver operating curve = AUROC =
      0.872, specificity = Sp(%) = 90.2, sensitivity = Sn(%) = 70.6, and overall
      accuracy = Ac(%) = 87.7 in training series. The model also have Sp(%) = 90.1,
      Sn(%) = 71.4, and Ac(%) = 87.8 in external validation series. The model use PT
      operators based on multicondition moving averages to capture all the complexity
      of the data set. We also compared the model with nonlinear artificial neural
      network (ANN) models obtaining similar results. This confirms the hypothesis of a
      linear relationship between the PT operators and the classification as anticancer
      compounds in different combinations of assay conditions. Last, we compared the
      model with other PTML models reported in the literature concluding that this is
      the only one PTML model able to predict activity against multiple types of
      cancer. This model is a simple but versatile tool for the prediction of the
      targets of anticancer compounds taking into consideration multiple combinations
      of experimental conditions in preclinical assays.

PMID- 30240187
TI  - Enhanced Diffusion and Chemotaxis at the Nanoscale.
AB  - Enzymes have been recently proposed to have mechanical activity associated with
      their chemical activity. In a number of recent studies, it has been reported that
      enzymes undergo enhanced diffusion in the presence of their corresponding
      substrate when this substrate is uniformly distributed in solution. Moreover, if
      the concentration of the substrate is nonuniform, enzymes and other small
      molecules have been reported to show chemotaxis (biased stochastic movement in
      the direction of the substrate gradient), typically toward higher concentrations
      of this substrate, with a few exceptions. The underlying physical mechanisms
      responsible for enhanced diffusion and chemotaxis at the nanoscale, however, are
      still not well understood. Understanding these processes is important both for
      fundamental biological research, for example, in the context of spatial
      organization of enzymes in metabolic pathways (metabolon formation), as well as
      for engineering applications, such as in the design of new vehicles for targeted
      drug delivery. In this Account, we will review the available experimental
      observations of both enhanced diffusion and chemotaxis, and we will discuss
      critically the different theories that have been proposed to explain the two. We
      first focus on enhanced diffusion, beginning with an overview of the experimental
      results. We then discuss the two main types of mechanisms that have been
      proposed, namely, active mechanisms relying on the catalytic step of the
      enzymatic reaction and equilibrium mechanisms, which consider the reversible
      binding and unbinding of the substrate to the enzyme. We put particular emphasis
      on an equilibrium model recently introduced by us, which describes how the
      diffusion of dumbbell-like modular enzymes can be enhanced in the presence of
      substrate thanks to a binding-induced reduction of the internal fluctuations of
      the enzyme. We then turn to chemotaxis, beginning with an overview of the
      experimental evidence for the chemotaxis of enzymes and small molecules, followed
      by a description of a number of shortcomings and pitfalls in the thermodynamic
      and phenomenological models for chemotaxis introduced in those and other works in
      the literature. We then discuss a microscopic model for chemotaxis including both
      noncontact interactions and specific binding between enzyme and substrate
      recently developed by us, which overcomes many of these shortcomings and is
      consistent with the experimental observations of chemotaxis. Finally, we show
      that the results of this model may be used to engineer chemically active
      macromolecules that are directed in space via patterning of the concentrations of
      their substrates.

PMID- 30240188
TI  - Discovery and Functional Characterization of a Yeast Sugar Alcohol Phosphatase.
AB  - Sugar alcohols (polyols) exist widely in nature. While some specific sugar
      alcohol phosphatases are known, there is no known phosphatase for some important
      sugar alcohols (e.g., sorbitol-6-phosphate). Using liquid chromatography-mass
      spectrometry-based metabolomics, we screened yeast strains with putative
      phosphatases of unknown function deleted. We show that the yeast gene YNL010W,
      which has close homologues in all fungi species and some plants, encodes a sugar
      alcohol phosphatase. We term this enzyme, which hydrolyzes sorbitol-6-phosphate,
      ribitol-5-phosphate, and (d)-glycerol-3-phosphate, polyol phosphatase 1 or PYP1.
      Polyol phosphates are structural analogs of the enediol intermediate of
      phosphoglucose isomerase (Pgi). We find that sorbitol-6-phosphate and ribitol-5
      phosphate inhibit Pgi and that Pyp1 activity is important for yeast to maintain
      Pgi activity in the presence of environmental sugar alcohols. Pyp1 expression is
      strongly positively correlated with yeast growth rate, presumably because faster
      growth requires greater glycolytic and accordingly Pgi flux. Thus, yeast express
      the previously uncharacterized enzyme Pyp1 to prevent inhibition of glycolysis by
      sugar alcohol phosphates. Pyp1 may be useful for engineering sugar alcohol
      production.

PMID- 30240189
TI  - MoS2 Quantum Dot/Graphene Hybrids for Advanced Interface Engineering of a
      CH3NH3PbI3 Perovskite Solar Cell with an Efficiency of over 20.
AB  - Interface engineering of organic-inorganic halide perovskite solar cells (PSCs)
      plays a pivotal role in achieving high power conversion efficiency (PCE). In
      fact, the perovskite photoactive layer needs to work synergistically with the
      other functional components of the cell, such as charge transporting/active
      buffer layers and electrodes. In this context, graphene and related two
      dimensional materials (GRMs) are promising candidates to tune "on demand" the
      interface properties of PSCs. In this work, we fully exploit the potential of
      GRMs by controlling the optoelectronic properties of molybdenum disulfide (MoS2)
      and reduced graphene oxide (RGO) hybrids both as hole transport layer (HTL) and
      active buffer layer (ABL) in mesoscopic methylammonium lead iodide (CH3NH3PbI3)
      perovskite (MAPbI3)-based PSCs. We show that zero-dimensional MoS2 quantum dots
      (MoS2 QDs), derived by liquid phase exfoliated MoS2 flakes, provide both hole
      extraction and electron-blocking properties. In fact, on one hand, intrinsic n
      type doping-induced intraband gap states effectively extract the holes through an
      electron injection mechanism. On the other hand, quantum confinement effects
      increase the optical band gap of MoS2 (from 1.4 eV for the flakes to >3.2 eV for
      QDs), raising the minimum energy of its conduction band (from -4.3 eV for the
      flakes to -2.2 eV for QDs) above the one of the conduction band of MAPbI3
      (between -3.7 and -4 eV) and hindering electron collection. The van der Waals
      hybridization of MoS2 QDs with functionalized reduced graphene oxide (f-RGO),
      obtained by chemical silanization-induced linkage between RGO and (3
      mercaptopropyl)trimethoxysilane, is effective to homogenize the deposition of
      HTLs or ABLs onto the perovskite film, since the two-dimensional nature of RGO
      effectively plugs the pinholes of the MoS2 QD films. Our "graphene interface
      engineering" (GIE) strategy based on van der Waals MoS2 QD/graphene hybrids
      enables MAPbI3-based PSCs to achieve a PCE up to 20.12% (average PCE of 18.8%).
      The possibility to combine quantum and chemical effects into GIE, coupled with
      the recent success of graphene and GRMs as interfacial layer, represents a
      promising approach for the development of next-generation PSCs.

PMID- 30240190
TI  - Well-Defined Palladium(II)-NHC Precatalysts for Cross-Coupling Reactions of
      Amides and Esters by Selective N-C/O-C Cleavage.
AB  - Transition-metal-catalyzed cross-coupling reactions represent a most powerful
      tool for the rapid construction of C-C and C-X bonds available to synthetic
      chemists. Recently, tremendous progress has been made in the burgeoning area of
      cross-coupling reactions of amides and esters enabled by regio- and
      chemoselective acyl C-X (X = N, O) cleavage using well-defined Pd(II)-NHC
      complexes. The use of N-heterocyclic carbenes as ligands in palladium-catalyzed
      cross-couplings permits reactions of amides and esters that were previously
      impossible using palladium or could be achieved only under harsh conditions.
      These reactions provide an attractive method to synthetic chemists to manipulate
      the traditionally inert amide and ester bonds with the broad cross-coupling
      generality inherent to palladium catalysis. Research in the area of cross
      coupling of stable acyl electrophiles can be broadly categorized by the type of
      electrophile undergoing the cross-coupling. Recent studies have shown that cross
      coupling of amides by transition-metal catalysis represents one of the most
      straightforward and wide-ranging ways of manipulating the classically inert amide
      bonds into generic acyl-metal intermediates that can be systematically exploited
      in cross-coupling reactions as a new paradigm in organic synthesis. The key to
      achieving high chemoselectivity of the process is control of amidic resonance (nN
      to piC?O* conjugation, rotation of ca. 15-20 kcal/mol in planar amides), enabling
      oxidative addition of the N-C amide bond to a metal in a rational and predictable
      manner. This mode of catalysis has been extended to C(acyl)-O cross-coupling
      reactions of aryl esters, where selective C-O bond cleavage is accomplished
      through a rational match of aryl ester electrophiles and nucleophilic metal
      catalysts. These two types of transition-metal-catalyzed cross-coupling reactions
      represent an attractive concept in synthetic chemistry because of the ubiquity of
      esters and amides as precursors in organic synthesis. Furthermore, the high
      stability of amides and esters provides unprecedented opportunities for
      orthogonal cross-coupling strategies in the presence of other electrophiles. In
      this Account, we highlight advances that have taken place in the past few years
      in the field of cross-coupling of amides and esters, focusing on both (1) the
      stereoelectronic properties of well-defined Pd(II)-NHC complexes that have been
      critical to realize this challenging cross-coupling manifold and (2) the role of
      the isomerization barrier of the acyl electrophiles undergoing the cross
      coupling. In a broader sense, the chemistry described here provides a practical
      approach to functionalize common amide and ester functional groups in organic
      synthesis and establishes straightforward access to acyl-metal intermediates that
      enable nonconventional cross-coupling strategies.

PMID- 30240191
TI  - Caught in the Act? Quantifying Biochemistry Inside and Outside of Biomolecular
      Condensates.

PMID- 30240192
TI  - Case Studies in Nanocluster Synthesis and Characterization: Challenges and
      Opportunities.
AB  - Atomically precise nanoclusters (APNCs) are an emerging area of nanoscience.
      Their monodispersity and well-defined arrangement of capping ligands facilitates
      the interrogation of their fundamental physical properties, allowing for the
      development of structure-function relationships, as well as their optimization
      for a variety of applications, including quantum computing, solid-state memory,
      catalysis, sensing, and imaging. However, APNCs present several unique synthetic
      and characterization challenges. For example, nanocluster syntheses are
      infamously low yielding and often generate complicated mixtures. This combination
      of factors makes nanocluster purification and characterization more difficult
      than that of typical inorganic or organometallic complexes. Yet, while this fact
      is undoubtedly true, the past lessons learned from the characterization of
      inorganic complexes are still useful today. In this Account, we discuss six case
      studies taken from the recent literature in an attempt to identify common
      challenges and pitfalls encountered in APNC synthesis and characterization. For
      example, we show that several reducing agents employed in APNC synthesis,
      including the commonly used reagent NaBH4, do not always behave as anticipated.
      Indeed, we highlight one case where NaBH4 reduces the ligand and not the metal
      center, and other cases where NaBH4 acts as a Bronstead base instead of a
      reducing agent. In addition, we have identified several instances where the use
      of phase transfer agents, which were added to mediate APNC formation, played no
      role in the nanocluster synthesis, and likely made the isolation of pure material
      more difficult. We have also identified several cases of cluster
      misidentification driven by spurious or ambiguous characterization data, most
      commonly collected by mass spectrometry. To address these challenges, we propose
      that the nanocluster community adopt a standard protocol of characterization,
      similar to those used by the organometallic and coordination chemistry
      communities. This protocol requires that many complementary techniques be used in
      concert to confirm formulation, structure, and analytical purity of APNC samples.
      Two techniques that are underutilized in this regard are combustion analysis and
      NMR spectroscopy. NMR spectroscopy, in particular, can provide information on
      purity and formulation that are difficult to collect with any other technique. X
      ray absorption spectroscopy is another powerful method of nanocluster
      characterization, especially in cases where single crystals for X-ray diffraction
      are not forthcoming. Chromatographic techniques can also be extremely valuable
      for assessing purity, but are rarely used during APNC characterization. Our goal
      with this Account is to begin a discussion with respect to the best protocols for
      nanocluster synthesis and characterization. We believe that embracing a standard
      characterization protocol would make APNC synthesis more reliable, thereby
      accelerating their integration into a variety of technologies.

PMID- 30240194
TI  - Low Solids Emulsion Gels Based on Nanocellulose for 3D-Printing.
AB  - Multiphase (emulsion) gels with internal phase fractions between 0.1 and 0.5 were
      formulated at low loadings of cellulose nanofibrils (CNF), alginate, and
      polylactide (PLA). Their properties (rheology and morphology) fitted those of
      inks used for direct ink writing (DIW). The effect of formulation and composition
      variables were elucidated after printing cubic scaffolds and other solid designs.
      The distinctive microstructures that were developed allowed high printing
      fidelity and displayed limited shrinkage after room temperature and freeze-drying
      (0 and 5% shrinkage in the out-of-plane and in-plane directions upon freeze
      drying, respectively). The CNF added in the continuous phase was shown to be
      critical to achieve rheology control as an effective interfacial stabilizer and
      to ensure the printability of the ink toward high structural reliability. We
      found that the extent of shape retention of the dried scaffolds resulted from the
      tightly locked internal structure. The PLA that was initially added in the
      nonpolar or organic phase (0 to 12%) was randomly embedded in the entire
      scaffold, providing a strong resistance to shrinkage during the slow water
      evaporation at ambient temperature. No surface collapse or lateral deformation of
      the dried scaffolds occurred, indicating that the incorporation of PLA limited
      drying-induced shape failure. It also reduced compression strain by providing
      better CNF skeletal support, improving the mechanical strength. Upon rewetting,
      the combination of the hydrophilicity imparted by CNF and alginate together with
      the highly porous structure of the 3D material and the internal microchannels
      contributed to high water absorption via capillary and other phenomena (swelling
      % between ~400 and 900%). However, no shape changes occurred compared to the
      initial 3D-printed shape. The swelling of the scaffolds correlated inversely with
      the PLA content in the precursor emulsion gel, providing a means to regulate the
      interaction with water given its low surface energy. Overall, the results
      demonstrate that by compatibilization of the CNF-based hydrophilic and the PLA
      based hydrophobic components, it is possible to achieve shape control and
      retention upon 3D printing, opening the possibility of adopting low-solids inks
      for DIW into dry objects. The dryable CNF-based 3D structural materials absorb
      water while being able to support load (high elastic modulus) and maintain the
      shape upon hydration.

PMID- 30240193
TI  - Selective Uptake Into Drug Resistant Mammalian Cancer by Cell Penetrating Peptide
      Mediated Delivery.
AB  - Research over the past decade has identified several of the key limiting features
      of multidrug resistance (MDR) in cancer therapy applications, such as evolving
      glycoprotein receptors at the surface of the cell that limit therapeutic uptake,
      metabolic changes that lead to protection from multidrug resistant mediators
      which enhance degradation or efflux of therapeutics, and difficulty ensuring
      retention of intact and functional drugs once endocytosed. Nanoparticles have
      been demonstrated to be effective delivery vehicles for a plethora of therapeutic
      agents, and in the case of nucleic acid based agents, they provide protective
      advantages. Functionalizing cell penetrating peptides, also known as protein
      transduction domains, onto the surface of fluorescent quantum dots creates a
      labeled delivery package to investigate the nuances and difficulties of drug
      transport in MDR cancer cells for potential future clinical applications of
      diverse nanoparticle-based therapeutic delivery strategies. In this study, eight
      distinct cell penetrating peptides were used (CAAKA, HSV1-VP22, HIV-TAT, HIV
      gp41, Ku-70, hCT(9-32), integrin-beta3, and K-FGF) to examine the different
      cellular uptake profiles in cancer versus drug resistant melanoma (A375 & A375
      R), mesothelioma (MSTO & MSTO-R), and glioma (rat 9L and 9L-R, and human U87 &
      LN18) cell lines. The results of this study demonstrate that cell penetrating
      peptide uptake varies with drug resistance status and cell type, likely due to
      changes in cell surface markers. This study provides insight into developing
      functional nanoplatform delivery systems in drug resistant cancer models.

PMID- 30240195
TI  - Microenvironment-Responsive Magnetic Nanocomposites Based on Silver
      Nanoparticles/Gentamicin for Enhanced Biofilm Disruption by Magnetic Field.
AB  - Biofilms contribute to persistent bacterial infections as well as formidable
      resistances to conventional antibiotics. However, it is still a major challenge
      to establish an advanced antibacterial nanoplatform that can efficiently
      eradicate biofilms while overcoming bacterial resistances. Taking advantage of
      the stimuli-responsive technique and the magnetic guidance strategy, here we
      present a highly efficient nanoplatform for planktonic inactivation and biofilm
      disruption. The multilayer films consisting of antibiotic gentamicin (Gen),
      tannic acid, and silver nanoparticles (AgNPs) were fabricated and coated on
      magnetic nanoparticles via electrostatic interactions. To achieve controlled drug
      release and improved biocompatibility, biodegradable hyaluronic acid was capped
      on the outer surface as a responsive shell. In vitro release profiles suggested
      that the nanocomposites showed both enzyme and pH-responsive release properties.
      The nanoplatform could be employed as a powerful nanocarrier for small molecular
      Gen and AgNPs delivery and on-demand release in response to bacterial infection
      microenvironment. The nanocomposites also showed satisfying antibacterial
      capacities against planktonic Gram-positive Staphylococcus aureus and Gram
      negative Escherichia coli. Intriguingly, with magnetic field navigation (NdFeB,
      2000 gauss), the nanocomposites could be guided to handily penetrate into S.
      aureus biofilm and performed dual-responsive release, showing significantly
      enhanced biofilm disruption. Moreover, excess reactive oxygen species production
      resulting from the nanocomposites contributed to the decomposition of biofilm
      matrix and ultimate biofilm eradication. As a consequence, the ingenious
      antibacterial nanoplatform could be promising for combating biofilm infections
      while overcoming bacterial resistances with extra environmental factors such as
      magnetic field.

PMID- 30240196
TI  - Mechanisms of Humic Acid Fouling on Capacitive and Insertion Electrodes for
      Electrochemical Desalination.
AB  - Though electrochemical deionization technologies have been widely explored for
      brackish water desalination and selective ion removal, their sustained
      performance in the presence of foulants common to environmental waters remains
      unclear. This study investigates the fundamental mechanisms by which carbonaceous
      electrodes used in capacitive deionization and insertion electrodes used for high
      capacity selective ion removal are affected by the presence of humic acid (HA).
      We evaluate HA adsorption behavior and the resulting impact on the ion storage
      capacity and cycling stability of the electrode materials. We find that HA is
      primarily adsorbed to the mesopores of two carbonaceous electrodes with
      distinctly different pore structures, but that the ion storage and transport
      properties of the electrodes are not significantly impacted by HA adsorption. In
      contrast, HA adsorption resulted in sharp capacity decay for the insertion
      (Na4Mn9O18) electrode. We attribute this decay to both hindered Na+ ion diffusion
      to the insertion interface in the presence of adsorbed HA, as well as HA mediated
      electrode dissolution. These findings highlight the contrasting mechanisms for HA
      fouling of capacitive and insertion electrodes and suggest that insertion
      electrodes may be more susceptible to performance decline in electrochemical
      deionization of environmental waters.

PMID- 30240197
TI  - Distribution of Four Bioactive Flavonoids in Maize Tissues of Five Varieties and
      Correlation with Expression of the Biosynthetic Genes.
AB  - Flavonoids are characteristic in maize and have diverse biological functions. C
      Glycosylflavones are neuroprotective against beta-amyloid-induced tau
      hyperphosphorylation and neurotoxicity in SH-SY5Y cells, which is relevant to
      Alzheimer's disease prevention and treatment. The content of the flavonoids
      eriodictyol, luteolin, isoorientin, and maysin varied in pollens, silks, tassels,
      and seeds among five maize varieties. Eriodictyol content was high (51-322 ng/g
      dw) in pollens, while luteolin content was low (0.2-106 ng/g dw) in all four
      tissues. The isoorientin content was approximately 3- to 10-fold greater than
      eriodictyol in pollens and tassels, particularly in the hybrid M1 and sweet corn
      M5 varieties. Maysin content was high in most silks and tassels. The differential
      expression of five genes involved in the maysin biosynthesis correlated well with
      the profiles of the four flavonoids among tissues and varieties. The present
      study offers valuable data for maize breeding and the use of maize flavonoids as
      functional food components.

PMID- 30240198
TI  - Identification and Quantitation of Four New 2-Alkylthiazolidine-4-carboxylic
      Acids Formed in Orange Juice by a Reaction of Saturated Aldehydes with Cysteine.
AB  - Despite several technological efforts to maximize the quality and shelf life of
      chilled stored not-from-concentrate orange juice, changes in the overall aroma
      profile might occur during storage. Besides the degradation of terpenoids, a loss
      of the aroma-active aldehydes, hexanal, octanal, nonanal, and decanal as well-as
      of 1-penten-3-one were recently confirmed as a major cause for the changes in the
      aroma profile of orange juice even during storage under aseptic conditions at 0 
      degrees C. To unravel the fate of the aroma-active aldehydes, model experiments
      were carried out considering the oxidation into the corresponding acids as well
      as a reaction with free amino acids present in orange juice. The oxidation into
      the acids could be confirmed by isotope labeling experiments; additionally, the
      reaction of the four aldehydes mentioned above with l-cysteine yielded four new
      compounds identified as 2-alkylsubstituted thiazolidine-4-carboxylic acids. Their
      quantitation in orange juice samples by newly developed stable isotope dilution
      assays revealed that these acids were already present in the fresh samples but
      were considerably increased after storage. Labeling experiments in orange juice
      administered with either labeled octanal or labeled cysteine confirmed that the
      reaction quickly occurs in the juice. The data contribute another puzzle piece to
      the loss of aroma-active aldehydes during orange juice storage, which may also be
      relevant in other foods.

PMID- 30240200
TI  - Cell-Permeable Activity-Based Ubiquitin Probes Enable Intracellular Profiling of
      Human Deubiquitinases.
AB  - Advancement in our knowledge of deubiquitinases (DUBs) and their biological
      functions requires biochemical tools permitting interrogation of DUB activities
      under physiologically relevant conditions. Activity-based DUB probes (DUB ABPs)
      have been widely used in investigating the function and activity of DUBs.
      However, most ubiquitin (Ub)-based DUB ABPs are not cell-permeable, limiting
      their utility to purified proteins and cell lysates. Lysis of cells usually leads
      to dilution of the cytoplasm and disruption of the normal cellular organization,
      which may alter the activity of many DUBs and DUB complexes. Here, we report a
      new class of cell-permeable DUB ABPs that enable intracellular DUB profiling. We
      used a semisynthetic approach to generate modular ubiquitin-based DUB probes
      containing a reactive warhead for covalent trapping of DUBs with a catalytic
      cysteine. We employed cell-penetrating peptides (CPPs), particualrly cyclic
      polyarginine (cR10), to deliver the DUB ABPs into cells, as confirmed using live
      cell fluorescence microscopy and DUB ABPs containing a fluorophore at the C
      terminus of Ub. In comparison to TAT, enhanced intacellular delivery was observed
      through conjugation of a cyclic polyarginine (cR10) to the N-terminus of
      ubiquitin via a disulfide linkage. Using the new cell-permeable DUB ABPs, we
      carried out DUB profiling in intact HeLa cells, and identified active DUBs using
      immunocapture and label-free quantitative mass spectrometry. Additionally, we
      demonstrated that the cell-permeable DUB ABPs can be used in assessing the
      inhibition of DUBs by small-molecule inhibitors in intact cells. Our results
      indicate that cell-permeable DUB ABPs hold great promise in providing a better
      understanding of the cellular functions of DUBs and advancing drug discovery
      efforts targeting human DUBs.

PMID- 30240199
TI  - Mechanism and Implication of the Sorption of Perfluorooctanoic Acid by Varying
      Soil Size Fractions.
AB  - Sorption of perfluorooctanoic acid (PFOA), a toxic and persistent organic
      pollutant, by various size fractions of an agricultural soil at environmentally
      relevant concentrations was evaluated. PFOA sorption to all fractions involved
      both film diffusion and intraparticle diffusion with the rate-limiting step by
      the latter. PFOA isotherm data fitted a linear model. Organic matter (OM), cation
      exchange capacity, pore volume, and the Brunauer-Emmett-Teller area played key
      roles in PFOA sorption. The sorption capacity followed the order of humic acid >
      clay (0.15-4.4 mm) > fine silt (1.9-39.8 mm) > coarse silt (17.3-79.4 mm) > fine
      sand (45.7-316.2 mm) > coarse sand (120-724.4 mm), opposite to their
      contributions to overall PFOA sorption due to the influence of their percentage
      weight in the original soil. Percentage OM content was the dominant factor
      controlling the fraction contributions to overall PFOA sorption, demonstrating
      influence of the hydrophobic force on sorption. PFOA should be highly mobile and
      bioavailable in soil-crop systems due to the low log Koc values.

PMID- 30240201
TI  - Oral Administration of Salecan-Based Hydrogels for Controlled Insulin Delivery.
AB  - We present an improved type of food gum (salecan) based hydrogels for oral
      delivery of insulin. Structural hydrogel formation was assessed with Fourier
      transform infrared spectroscopy, thermogravimetric analysis, and X-ray
      diffraction. We found that the hydrogel modulus, morphology, and swelling
      properties can be controlled by varying the salecan dose during hydrogel
      formation. Insulin was introduced into the hydrogel using a swelling-diffusion
      approach and then further used a drug prototype. In vitro insulin release
      profiles demonstrated that the release of entrapped insulin was suppressed in
      acidic conditions but markedly increased at neutral pH. Cell viability and
      toxicity tests revealed that the salecan hydrogel constructs were biocompatible.
      Oral administration of insulin-loaded salecan hydrogels in diabetic rats resulted
      in a sustained decrease of fasting plasma glucose levels over 6 h
      postadministration. For nondiabetic animals, the relative pharmacological
      bioavailability of insulin was significantly larger (6.24%, p < 0.05) for insulin
      loaded hydrogels compared to free insulin. These results encourage further
      development of salecan-based hydrogels as vehicles for controlled insulin
      delivery following oral administration.

PMID- 30240202
TI  - Template-Guided Protein Structure Prediction and Refinement Using Optimized
      Folding Landscape Force Fields.
AB  - When good structural templates can be identified, template-based modeling is the
      most reliable way to predict the tertiary structure of proteins. In this study,
      we combine template-based modeling with a realistic coarse-grained force field,
      AWSEM, that has been optimized using the principles of energy landscape theory.
      The Associative memory, Water mediated, Structure and Energy Model (AWSEM) is a
      coarse-grained force field having both transferable tertiary interactions and
      knowledge-based local-in-sequence interaction terms. We incorporate template
      information into AWSEM by introducing soft collective biases to the template
      structures, resulting in a model that we call AWSEM-Template. Structure
      prediction tests on eight targets, four of which are in the low sequence identity
      "twilight zone" of homology modeling, show that AWSEM-Template can achieve high
      resolution structure prediction. Our results also confirm that using a
      combination of AWSEM and a template-guided potential leads to more accurate
      prediction of protein structures than simply using a template-guided potential
      alone. Free energy profile analyses demonstrate that the soft collective biases
      to the template effectively increase funneling toward native-like structures
      while still allowing significant flexibility so as to allow for correction of
      discrepancies between the target structure and the template. A further stage of
      refinement using all-atom molecular dynamics augmented with soft collective
      biases to the structures predicted by AWSEM-Template leads to a further
      improvement of both backbone and side-chain accuracy by maintaining sufficient
      flexibility but at the same time discouraging unproductive unfolding events often
      seen in unrestrained all-atom refinement simulations. The all-atom refinement
      simulations also reduce patches of frustration of the initial predictions. Some
      of the backbones found among the structures produced during the initial coarse
      grained prediction step already have CE-RMSD values of less than 3 A with 90% or
      more of the residues aligned to the experimentally solved structure for all
      targets. All-atom structures generated during the following all-atom refinement
      simulations, which started from coarse-grained structures that were chosen
      without reference to any knowledge about the native structure, have CE-RMSD
      values of less than 2.5 A with 90% or more of the residues aligned for 6 out of 8
      targets. Clustering low energy structures generated during the initial coarse
      grained annealing picks out reliably structures that are within 1 A of the best
      sampled structures in 5 out of 8 cases. After the all-atom refinement, structures
      that are within 1 A of the best sampled structures can be selected using a simple
      algorithm based on energetic features alone in 7 out of 8 cases.

PMID- 30240203
TI  - Choice of Adaptive Sampling Strategy Impacts State Discovery, Transition
      Probabilities, and the Apparent Mechanism of Conformational Changes.
AB  - Interest in atomically detailed simulations has grown significantly with recent
      advances in computational hardware and Markov state modeling (MSM) methods, yet
      outstanding questions remain that hinder their widespread adoption. Namely, how
      do alternative sampling strategies explore conformational space and how might
      this influence predictions generated from the data? Here, we seek to answer these
      questions for four commonly used sampling methods: (1) a single long simulation,
      (2) many short simulations run in parallel, (3) adaptive sampling, and (4) our
      recently developed goal-oriented sampling algorithm, FAST. We first develop a
      theoretical framework for analytically calculating the probability of discovering
      select states on simple landscapes, where we uncover the drastic effects of
      varying the number and length of simulations. We then use kinetic Monte Carlo
      simulations on a variety of physically inspired landscapes to characterize the
      probability of discovering particular states and transition pathways for each of
      the four methods. Consistently, we find that FAST simulations discover each
      target state with the highest probability, while traversing realistic pathways.
      Furthermore, we uncover the potential pathology that short parallel simulations
      sometimes predict an incorrect transition pathway by crossing large energy
      barriers that long simulations would typically circumnavigate. We refer to this
      pathology as "pathway tunneling". To protect against this phenomenon when using
      adaptive-sampling and FAST simulations, we introduce the FAST-string method. This
      method enhances sampling along the highest-flux transition paths to refine an
      MSMs transition probabilities and discriminate between competing pathways.
      Additionally, we compare the performance of a variety of MSM estimators in
      describing accurate thermodynamics and kinetics. For adaptive sampling, we
      recommend simply normalizing the transition counts out of each state after adding
      small pseudocounts to avoid creating sources or sinks. Lastly, we evaluate
      whether our insights from simple landscapes hold for all-atom molecular dynamics
      simulations of the folding of the lambda-repressor protein. Remarkably, we find
      that FAST-contacts predicts the same folding pathway as a set of long simulations
      but with orders of magnitude less simulation time.

PMID- 30240204
TI  - Robustness, Selective Gas Separation, and Nitrobenzene Sensing on Two Isomers of
      Cadmium Metal-Organic Frameworks Containing Various Metal-O-Metal Chains.
AB  - Poor stability has been one of the major difficulties affecting to the practical
      application of metal-organic frameworks (MOFs). In this work, we obtained two 3D
      structurally isomeric Cd-MOFs, {[Cd6(NH2Me2)2(PTB)4(HCOO)2(H2O)].(DMF)13.(H2O)4}
      n (FJU-35) and {[Cd6(NH2Me2)2(PTB)4(HCOO)2].(DMF)6.(H2O)2} n (FJU-36) (H3PTB =
      pyridine-2,4,6-tribenzoic acid) containing different CdII-O-CdII chains by
      varying the addition agents. FJU-35 with coordinated solvent and formate in
      asymmetric MU3-eta1:eta2 coordination mode within the CdII-O-CdII chains is
      vulnerable to external attacks and is apt to collapse after activation, while FJU
      36 with no coordinated solvent in the CdII-O-CdII chains but fully protected by
      the carboxylates from the ligands and the symmetric formate in the coordination
      mode MU3-eta2:eta2 is stable, and its activated sample shows efficient separation
      of C2H2/CH4 and C2H2/CO2 mixtures. Conversely, FJU-35 with more vulnerability is
      more sensitive to the detection of nitrobenzene than FJU-36.

PMID- 30240205
TI  - New Degradation Pathways of the Key Aroma Compound 1-Penten-3-one during Storage
      of Not-from-Concentrate Orange Juice.
AB  - 1-Penten-3-one with its fresh and pungent smell at a very low odor threshold of
      0.94 MUg/L water has been characterized as impact aroma compound in many foods,
      such as grapefruit, orange juice, black tea, olive oil, or tomatoes. While its
      importance to the fresh sensation of unstored not-from-concentrate (NFC) orange
      juice was recently confirmed by aroma recombinates, a total loss was determined
      already after 4 weeks in NFC orange juice stored at 0  degrees C. Until now, the
      degradation pathway of this compound has not been clarified. Systematic model
      studies resulted in the identification of 1-hydroxy-3-pentanone and 4-hydroxy-3,8
      decanedione as degradation products as well as S-(3-oxopentyl)-l-cysteine in the
      presence of the amino acid. In orange juice samples, it was found that the
      elevated content of 1-hydroxy-3-pentanone indicates a thermal processing, while S
      (3-oxopentyl)-l-cysteine showed a significant increase during cold storage.
      Additionally, both compounds were identified in other food samples, such as
      commercial orange juices, pickled olives and olive oil, fresh tomatoes and
      commercial tomato juice, and black tea.

PMID- 30240206
TI  - Cooperative Metal-Ligand Hydroamination Catalysis Supported by C-H Activation in
      Cyclam Zr(IV) Complexes.
AB  - Complexes of the type (R2Cyclam)ZrCl2 (where R = CH2?C(H)CH2 (All), CH2?C(Me)CH2
      (MeAll), and PhCH2 (Bn)) react with suitable Grignard reagents to produce the
      corresponding alkyl derivatives (R2Cyclam)ZrR'2 (R' = Me, CH2Ph). Thermally
      induced double metalation of the pending arms of the cyclam ligand led to the
      formation of complexes ((CH?C(H)CH2)2Cyclam)Zr, 14, ((CH?C(Me)CH2)2Cyclam)Zr, 15,
      or ((C6H4CH2)2Cyclam)Zr, 16. These reactions proceed through C(sp2)-H bond
      activation and R'H elimination and convert the original dianionic
      tetracoordinated cyclam-based ligands in tetraanionic hexacoordinated ligands
      that establish two new Zr-C bonds. The cleavage of the Zr-C bonds may be readily
      achieved by treatment of the bis( ortho-metalated) species 16 with protic
      substrates ( tert-butanol, phenol, thiophenol, aniline, benzophenone hydrazone,
      pyrazole, and N, N'-diphenylhydrazine), to give rise to (Bn2Cyclam)ZrX2 complexes
      (X = OtBu, OPh, SPh, NHPh, NHNCPh2, C3H3N2, N, N'-PhNNPh). In catalytic
      conditions, complexes (All2Cyclam)Zr(NMe2)2, 14, 15, or 16 convert 2,2-diphenyl
      pent-4-enylamine to 2-methyl-4,4-diphenylpyrrolidine with 100% selectivity and
      conversion values varying between 61 and 88% in 4.5 h, at 115  degrees C.
      Complexes 14 and 15, which display metalated allyl and methallyl pending groups
      on the cyclam ring, are the most active species (1.7 < TOF < 2.0 h-1). The
      mechanism of this reaction was studied by density functional theory that revealed
      two competitive paths, one proceeding through an imido intermediate and another
      that occurs via an amido ligand. Both cases represent cooperative mechanisms with
      active participation of the cyclam, as proton exchange between the coordinated
      substrate and the ligand side arm with reversible C-H activation is a crucial
      feature of the mechanism.

PMID- 30240207
TI  - Vitamin E Encapsulation in Plant-Based Nanoemulsions Fabricated Using Dual
      Channel Microfluidization: Formation, Stability, and Bioaccessibility.
AB  - In this study, vitamin E was encapsulated in oil-in-water nanoemulsions
      fabricated using a dual-channel microfluidizer. A long chain triacylglycerol
      (corn oil) was used as a carrier oil and a biosurfactant (quillaja saponin) was
      used as a natural emulsifier. The impact of vitamin-to-carrier oil ratio on the
      formation, storage stability, and bioaccessibility of the nanoemulsions was
      determined. The lipid droplet size formed during homogenization increased with
      increasing vitamin content, which was attributed to a large increase in lipid
      phase viscosity. The storage stability of the nanoemulsions decreased as the
      vitamin content increased because the larger lipid droplets creamed faster. The
      rate and extent of lipid hydrolysis in the small intestine decreased as the
      vitamin content increased, probably because the vitamin molecules inhibited the
      ability of lipase to reach the triacylglycerols inside the lipid droplets.
      Vitamin bioaccessibility decreased as the vitamin level in the lipid phase
      increased, which was attributed to the reduced level of mixed micelles available
      to solubilize the tocopherols. The optimized nanoemulsion-based delivery system
      led to a relatively high vitamin bioaccessibility (53.9%). This research provides
      valuable information for optimizing delivery systems to increase the
      bioaccessibility of oil-soluble vitamins.

PMID- 30240208
TI  - Efficient Sampling and Characterization of Free Energy Landscapes of Ion-Peptide
      Systems.
AB  - Proteins that influence nucleation, growth, or polymorph selection during
      biomineralization processes are often rich in glutamic- or aspartic acid. Here,
      the interactions between carboxylate side chains and ions lead to an interplay of
      peptide conformations and ion structuring in solution. Molecular dynamics
      simulations are an ideal tool to mechanistically investigate these processes.
      Unfortunately, the formation of strong ion-peptide contacts and ion bridges
      drastically impedes structural reorganization of ionic bonds and conformational
      transitions of the polymers. Thus, to obtain a complete thermodynamical picture
      of such systems, enhanced sampling techniques become necessary as well as the
      methods to characterize the conformational states of these partially disordered
      polymer-ion systems. Here, we propose a new set of Hamiltonian replica exchange
      (HRE) parameters for efficient simulations of peptide-ion systems, with an
      aspartic acid trimer in the presence of Ca2+ and Cl- ions as a test system. We
      introduce dimensionality reduction and clustering strategies to characterize the
      states of such a multicomponent system and to analyze the outcome of the proposed
      HRE with different reweighting methods.

PMID- 30240210
TI  - Systematic Comparison of Amber and Rosetta Energy Functions for Protein Structure
      Evaluation.
AB  - An accurate energy function is an essential component of biomolecular structural
      modeling and design. The comparison of differently derived energy functions
      enables analysis of the strengths and weaknesses of each energy function and
      provides independent benchmarks for evaluating improvements within a given energy
      function. We compared the molecular mechanics Amber empirical energy function to
      two versions of the Rosetta energy function (talaris2014 and REF2015) in decoy
      discrimination and loop modeling tests. In decoy discrimination tests, both
      Rosetta and Amber (ff14SBonlySC) energy functions performed well in scoring the
      native state as the lowest energy conformation in many cases, but several false
      minima were found in with both talaris2014 and Amber ff14SBonlySC scoring
      functions. The current default version of the Rosetta energy function, REF2015,
      which is parametrized on both small molecule and macromolecular benchmark sets to
      improve decoy discrimination, performs significantly better than talaris2014,
      highlighting the improvements made to the Rosetta scoring approach. There are no
      cases in Rosetta REF2015, and 8/140 cases in Amber, where a false minimum is
      found that is absent in the alternative landscape. In loop modeling tests, Amber
      ff14SBonlySC and REF2015 perform equivalently, although false minima are detected
      in several cases for both. The balance between dihedral, electrostatic, solvation
      and hydrogen bonding scores contribute to the existence of false minima. To take
      advantage of the semi-orthogonal nature of the Rosetta and Amber energy
      functions, we developed a technique that combines Amber and Rosetta
      conformational rankings to predict the most near-native model for a given
      protein. This algorithm improves upon predictions from either energy function in
      isolation and should aid in model selection for structure evaluation and loop
      modeling tasks.

PMID- 30240211
TI  - Tandem Allylation/1,2-Boronate Rearrangement for the Asymmetric Synthesis of
      Indolines with Adjacent Quaternary Stereocenters.
AB  - A three-component coupling using lithiated indoles, boronate esters and allylic
      acetates generates chiral indolines with adjacent quaternary stereocenters.
      Successful stereocontrol required the use of phosphoramidite ligands not
      previously described for organopalladium chemistry. Mechanistic studies indicate
      a monodentate PdL intermediate, and a stepwise allylation-aryl/alkyl migration. A
      protodeborylation strategy was used to install a C-H bond in place of the C-B
      bond. A photoredox coupling was used to replace C-B bond with a C-C bond in a
      highly diastereoselective manner. In the specific case of methyl-vinyl ketone, a
      novel radical-mediated annulation provides polycyclic products with high enantio-
      and diastereoselectivity.

PMID- 30240209
TI  - Kinematic Flexibility Analysis: Hydrogen Bonding Patterns Impart a Spatial
      Hierarchy of Protein Motion.
AB  - Elastic network models (ENMs) and constraint-based, topological rigidity analysis
      are two distinct, coarse-grained approaches to study conformational flexibility
      of macromolecules. In the two decades since their introduction, both have
      contributed significantly to insights into protein molecular mechanisms and
      function. However, despite a shared purpose of these approaches, the topological
      nature of rigidity analysis, and thereby the absence of motion modes, has impeded
      a direct comparison. Here, we present an alternative, kinematic approach to
      rigidity analysis, which circumvents these drawbacks. We introduce a novel
      protein hydrogen bond network spectral decomposition, which provides an
      orthonormal basis for collective motions modulated by noncovalent interactions,
      analogous to the eigenspectrum of normal modes. The zero modes decompose proteins
      into rigid clusters identical to those from topological rigidity, while nonzero
      modes rank protein motions by their hydrogen bond collective energy penalty. Our
      kinematic flexibility analysis bridges topological rigidity theory and ENM,
      enabling a detailed analysis of motion modes obtained from both approaches.
      Analysis of a large, structurally diverse data set revealed that collectivity of
      protein motions, reported by the Shannon entropy, is significantly reduced for
      rigidity theory compared to normal mode approaches. Strikingly, kinematic
      flexibility analysis suggests that the hydrogen bonding network encodes a protein
      fold specific, spatial hierarchy of motions, which goes nearly undetected in ENM.
      This hierarchy reveals distinct motion regimes that rationalize experimental and
      simulated protein stiffness variations. Kinematic motion modes highly correlate
      with reported crystallographic B factors and molecular dynamics simulations of
      adenylate kinase. A formal expression for changes in free energy derived from the
      spectral decomposition indicates that motions across nearly 40% of modes obey
      enthalpy-entropy compensation. Taken together, our results suggest that hydrogen
      bond networks have evolved to modulate protein structure and dynamics, which can
      be efficiently probed by kinematic flexibility analysis.

PMID- 30240212
TI  - Tuned Range-Separated Density Functional Theory and Dyson Orbital Formalism for
      Photoelectron Spectra.
AB  - Photoelectron spectroscopy represents a valuable tool to analyze structural and
      dynamical changes in molecular systems. Comprehensive interpretation of
      experimental data requires, however, involvement of reliable theoretical
      modeling. In this work, we present a protocol based on the combination of well
      established linear-response time-dependent density functional theory and Dyson
      orbital formalism for the accurate prediction of both ionization energies and
      intensities. Essential here is the utilization of the optimally tuned range
      separated hybrid density functionals, improving the ionization potentials not
      only of frontier but also of the deeper lying orbitals. In general, the protocol
      provides accurate results as illustrated by comparison to experiments for several
      gas-phase molecules, belonging to different classes. Further, we analyze possible
      pitfalls of this approach and, namely, discuss the ambiguities in the choice of
      optimal range-separation parameters, the influence of the stability of the ground
      state, and the spin contamination issues as possible sources of inaccuracies.

PMID- 30240213
TI  - Performance and Scope of Perturbative Corrections to Random-Phase Approximation
      Energies.
AB  - It has been suspected since the early days of the random-phase approximation
      (RPA) that corrections to RPA correlation energies result mostly from short-range
      correlation effects and are thus amenable to perturbation theory. Here we test
      this hypothesis by analyzing formal and numerical results for the most common
      beyond-RPA perturbative corrections, including the bare second-order exchange
      (SOX), second-order screened exchange (SOSEX), and approximate exchange kernel
      (AXK) methods. Our analysis is facilitated by efficient and robust algorithms
      based on the resolution-of-the-identity (RI) approximation and numerical
      frequency integration, which enable benchmark beyond-RPA calculations on medium-
      and large-size molecules with size-independent accuracy. The AXK method
      systematically improves upon RPA, SOX, and SOSEX for reaction barrier heights,
      reaction energies, and noncovalent interaction energies of main-group compounds.
      The improved accuracy of AXK compared with SOX and SOSEX is attributed to
      stronger screening of bare SOX in AXK. For reactions involving transition-metal
      compounds, particularly 3d transition-metal dimers, the AXK correction is too
      small and can even have the wrong sign. These observations are rationalized by a
      measure alpha of the effective coupling strength for beyond-RPA correlation. When
      the effective coupling strength increases beyond a critical alpha value of
      approximately 0.5, the RPA errors increase rapidly and perturbative corrections
      become unreliable. Thus, perturbation theory can systematically correct RPA but
      only for systems and properties qualitatively well captured by RPA, as indicated
      by small alpha values.

PMID- 30240214
TI  - Tandem Achmatowicz Rearrangement and Acetalization of 1-[5-(Hydroxyalkyl)-furan-2
      yl]-cyclobutanols Leading to Dispiroacetals and Subsequent Ring-Expansion to Form
      6,7-Dihydrobenzofuran-4(5 H)-ones.
AB  - Herein, we report a one-pot protocol for the synthesis of dispiroacetals 4
      bearing a cyclobutane motif via tandem Achmatowicz rearrangement and
      acetalization of 1-[5-(hydroxyalkyl)-furan-2-yl]-cyclobutanols 3 with m-CPBA as
      the oxidant and AgSbF6 as an additive to promote the cyclization step in an
      aqueous medium. Dispiroacetals 4 could subsequently undergo Lewis acid-catalyzed
      ring expansion and skeletal rearrangement to afford 6,7-dihydro-5 H-benzofuran-4
      ones 5.

PMID- 30240215
TI  - Sweet Confinement: Glucose and Carbohydrate Osmolytes in Reverse Micelles.
AB  - The research presented here reports the surprising observation that adding
      glucose and other carbohydrate osmolytes to the polar phase of water-containing
      reverse micelles causes the particles to shrink. This apparent change in reverse
      micelle size is attributed to two factors: an increase in the surface area per
      surfactant molecule induced by the presence of carbohydrate and changes in the
      particle shape eccentricity. The studies reported here not only focus on glucose
      but also explore other carbohydrate osmolytes, specifically ethylene glycol,
      glycerol, erythritol, xylitol, sorbitol, myo-inositol, and trehalose, in the
      nanoconfined environments of reverse micelles. Through two-dimensional proton
      nuclear Overhauser enhancement nuclear magnetic resonance spectroscopy, the
      osmolytes were determined to reside solvated in the aqueous interior of the
      reverse micelles. This paper reports the loading limit of carbohydrates into AOT
      [sodium bis(2-ethylhexyl)sulfosuccinate] reverse micelles, demonstrates the
      location of the carbohydrates in the reverse micelles, and shows an unexpected
      effect where the carbohydrates add to the reverse micelle volume without causing
      an apparent increase in the reverse micelle diameter.

PMID- 30240216
TI  - Preclinical Efficacy and Characterization of Candidate Vaccines for Treatment of
      Opioid Use Disorders Using Clinically Viable Carrier Proteins.
AB  - Vaccines may offer a new treatment strategy for opioid use disorders and opioid
      related overdoses. To speed translation, this study evaluates opioid conjugate
      vaccines containing components suitable for pharmaceutical manufacturing and
      compares analytical assays for conjugate characterization. Three oxycodone-based
      haptens (OXY) containing either PEGylated or tetraglycine [(Gly)4] linkers were
      conjugated to a keyhole limpet hemocyanin (KLH) carrier protein via carbodiimide
      (EDAC) or maleimide chemistry. The EDAC-conjugated OXY(Gly)4-KLH was most
      effective in reducing oxycodone distribution to the brain in mice. Vaccine
      efficacy was T cell-dependent. The lead OXY hapten was conjugated to the KLH,
      tetanus toxoid, diphtheria cross-reactive material (CRM), as well as the E. coli
      expressed CRM (EcoCRM) and nontoxic tetanus toxin heavy chain fragment C (rTTHc)
      carrier proteins. All vaccines induced early hapten-specific B cell expansion and
      showed equivalent efficacy against oxycodone in mice. However, some hapten
      protein conjugates were easier to characterize for molecular weight and size.
      Finally, heroin vaccines formulated with either EcoCRM or KLH were equally
      effective in reducing heroin-induced antinociception and distribution to the
      brain of heroin and its metabolites in mice. This study identifies vaccine
      candidates and vaccine components for further development.

PMID- 30240217
TI  - Probing Solvation-Induced Structural Changes in Conformationally Flexible
      Peptides: IR Spectroscopy of Gly3H+.(H2O).
AB  - IR predissociation spectroscopy of the Gly3H+(H2O) complex formed inside of a
      cryogenic ion trap reveals how the flexible model peptide structurally responds
      to solvation by a single water molecule. The resulting one-laser spectrum is
      quite congested, and the spectral analyses were assisted by both H2O/D2O
      substitution and IR-IR double resonance spectroscopy, revealing the presence of
      two contributing isomers and extensive anharmonic features. Comparisons to
      structures found via a systematic computational search identified the geometries
      of these two isomers. The major isomer, with all trans amide bonds and
      protonation on the terminal amine, represents ~90% of the overall population. It
      noticeably differs from the unsolvated Gly3H+, which exists in two isomeric
      forms: one with a cis amide bond and the other with protonation on an amide C?O.
      These results indicate that interactions with just one water molecule can induce
      significant structural changes, i.e., cis- trans amide bond rotation and proton
      migration, even as the clustering occurs within an 80 K cryogenic ion trap.
      Calculations of the isomerization pathways further reveal that the binding energy
      of the water molecule provides sufficient internal energy to overcome the
      barriers for the observed structural changes, and the minor solvation isomer
      results from a small fraction of the ions being kinetically trapped along one of
      the pathways.

PMID- 30240218
TI  - One-Pot Sequential [3 + 3] Dipolar Cycloaddition of Aldehyde or Ketone and
      Hydroxylamine with Spirocyclopropyl Oxindole.
AB  - A Sc(OTf)3-catalyzed highly diastereoselective one-pot sequential [3 + 3] dipolar
      cycloaddition reaction of aldehyde or ketone, N-alkyl hydroxylamine, and
      spirocyclopropyl oxindole is developed, allowing facile construction of
      spirocyclic oxindole-tetrahydro-1,2-oxazines with sufficient structural
      diversity. The corresponding catalytic enantioselective one-pot protocol of
      aldehydes is also reported, affording the desired adducts in up to 97% ee. The
      biological evaluation of selected oxindole-based spirocyclic tetrahydro-1,2
      oxazines revealed that they exerted cytotoxic effects on human prostate cancer
      cells with the capacity to inhibit NFkappaB signaling in prostate cancer cells.

PMID- 30240219
TI  - Lewis Acid-Catalyzed Malonate Addition onto 3-Hydroxy-2-oxindoles: Mechanistic
      Consideration and Synthetic Approaches to the Pyrroloindoline Alkaloids.
AB  - Metal triflate-catalyzed reactions of 3-hydroxy-2-oxindoles with a variety of
      malonates have been developed under mild conditions. The reaction afford a
      variety of 2-oxindoles sharing a C-3 quaternary center at the pseudobenzylic
      position in an operationally simple procedure. Control experiments using
      enantioenriched 3-hydroxy/methoxy 2-oxindoles (91% ee) afforded a malonate
      addition product in racemic form, clearly suggesting that the reaction proceeds
      through an in situ generated 2 H-indol-2-one intermediate (4a). Synthetic
      potential of this methodology has been shown by approaching the cyclotryptamine
      alkaloids linked with the aryl group at the pseudobenzylic position.

PMID- 30240220
TI  - Synthesis of Nitriles from Primary Amides or Aldoximes under Conditions of a
      Catalytic Swern Oxidation.
AB  - The preparation of nitriles from primary amides or aldoximes was achieved by
      using oxalyl chloride with a catalytic amount of dimethyl sulfoxide in the
      presence of Et3N. The reactions were complete within 1 h after addition at room
      temperature. A diverse range of cyano compounds were obtained in good to
      excellent yields, including aromatic, heteroaromatic, cyclic, and acyclic
      aliphatic species.

PMID- 30240221
TI  - Going the Distance: Long-Range Conductivity in Protein and Peptide Bioelectronic
      Materials.
AB  - Bioelectronic materials interface biomolecules, cells, organs, or organisms with
      electronic devices, and they represent an active and growing field of materials
      research. Protein and peptide nanostructures are ideal bioelectronic materials.
      They possess many of the properties required for biocompatibility across scales
      from enzymatic to organismal interfaces, and recent examples of supramolecular
      protein and peptide nanostructures exhibit impressive electronic properties. The
      ability of such natural and synthetic protein and peptide materials to conduct
      electricity over micrometer to centimeter length scales, however, is not readily
      understood from a conventional view of their amino acid building blocks. Distinct
      in structure and properties from solid-state inorganic and synthetic organic
      metals and semiconductors, supramolecular conductive proteins and peptides
      require careful theoretical treatment and experimental characterization methods
      to understand their electronic structure. In this review, we discuss theory and
      experimental evidence from recent literature describing the long-range conduction
      of electronic charge in protein and peptide materials. Electron transfer across
      proteins has been studied extensively, but application of models for such short
      range charge transport to longer distances relevant to bioelectronic materials
      are less well-understood. Implementation of electronic band structure and
      electron transfer formulations in extended biomolecular systems will be covered
      in the context of recent materials discoveries and efforts at characterization of
      electronic transport mechanisms.

PMID- 30240222
TI  - Palladium-Catalyzed C3-Arylations of 1 H- and 2 H-Pyrazolo[4,3- b]pyridines on
      Water.
AB  - Direct C3-arylation of 1 H-pyrazolo[4,3- b]pyridines and direct C3-arylation of 2
      H-pyrazolo[4,3- b]pyridines in water has been developed. A new protocol for a
      sequential C3-arylation procedure on a mixture of 1 H- and 2 H-pyrazolo[4,3-
      b]pyridines followed by in situ PMB cleavage has also been achieved. This
      procedure led to unprotected ( NH) C3-arylated 1 H-pyrazolo[4,3- b]pyridines in
      good yields.

PMID- 30240223
TI  - Iridium-Catalyzed Enantioselective and Diastereoselective Allylation of
      Dioxindoles: A One-Step Synthesis of 3-Allyl-3-hydroxyoxindoles.
AB  - An iridium-catalyzed asymmetric allylation of dioxindoles, 3-hydroxyoxindoles,
      regulated by prosthetic groups has been accomplished under mild conditions. The
      methodology is applicable to a diverse array of 3-hydroxyoxindole and cinnamyl
      acetate substrates. A range of 3-allyl-3-hydroxyoxindoles containing vicinal
      tetrasubstituted and trisubstituted stereocenters can be efficiently synthesized
      in one-step with excellent enantioselectivity (up to >99% enaniomeric excess
      (ee)) and good diastereoselectivity (up to 11:1 diastereomeric ratio (dr)).

PMID- 30240224
TI  - Conformational Equilibrium of Cinchonidine in C6D12 Solution. Alternative NMR/DFT
      Approach.
AB  - 1H NMR and 13C NMR chemical shifts as well as conformation dependent vicinal 1H
      1H spin-spin coupling constants for cinchonidine in a dilute C6D12 solution have
      been measured. These data have been interpreted in detail exploiting the results
      of the extensive quantum chemistry calculations of molecular geometry and NMR
      parameters of the molecule, performed using the density functional theory (DFT)
      B3LYP/6-311++G(2d,p) polarizable continuum model (PCM) level of theory. The
      experimental values of NMR parameters for cinchonidine have been reproduced very
      well in terms of parameters calculated for key conformers of this molecule.
      Simultaneously, the analysis has provided us with a lot of information on
      conformational equilibrium of cinchonidine in the investigated solution. These
      findings remain in general agreement with the conclusions of other works, based
      on NOESY spectra or other physicochemical data. Thus, a careful quantitative
      interpretation of easily measurable NMR chemical shifts can be an independent and
      valuable source of structural information even in such complex cases as
      cinchonidine in solution.

PMID- 30240226
TI  - Fundamental Link between beta Relaxation, Excess Wings, and Cage-Breaking in
      Metallic Glasses.
AB  - In glassy materials, the Johari-Goldstein secondary (beta) relaxation is crucial
      to many properties as it is directly related to local atomic motions. However, a
      long-standing puzzle remains elusive: why some glasses exhibit beta relaxations
      as pronounced peaks while others present as unobvious excess wings? Using
      microsecond atomistic simulation of two model metallic glasses (MGs), we
      demonstrate that such a difference is associated with the number of string-like
      collective atomic jumps. Relative to that of excess wings, we find that MGs
      having pronounced beta relaxations contain larger numbers of such jumps.
      Structurally, they are promoted by the higher tendency of cage-breaking events of
      their neighbors. Our results provide atomistic insights for different signatures
      of the beta relaxation that could be helpful for understanding the low
      temperature dynamics and properties of MGs.

PMID- 30240225
TI  - Functionalized Graphene Oxide Enables a High-Performance Bulk Heterojunction
      Organic Solar Cell with a Thick Active Layer.
AB  - Novel functionalized graphene oxide pi-pi stacking with conjugated polymers (P
      GO) is fabricated via a simple ethanol-mediated mixing method, leading to better
      dispersion in organic nonpolar solvents and bypassing the inherent restrictions
      of hydrophilicity and oleophobicity. We analyze the mechanism of the
      incorporation of P-GO into inverted organic solar cells (OSCs) based on a
      poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro
      2-[(2-ethylhexyl)carbonyl]thieno[3,4- b]thiophenediyl]] (PTB7):[6,6]-phenyl C71
      butyric acid methyl ester (PC71BM) system to investigate the possibility of high
      performance thick-film OSC fabrication. It is verified that the incorporation of
      P-GO into the PTB7:PC71BM blend films leads to a decreased pi-pi stacking
      distance, enlarged coherence length for polymer, and optimized phase separation,
      resulting in more effective charge dissociation, reduced bimolecular
      recombination, and more balanced charge transport. The OSCs with 1% P-GO
      incorporation demonstrate a thickness-insensitive fill factor (57.8%) and power
      conversion efficiency (PCE) (7.31%) even with 250 nm thick photoactive layers,
      leading to a dramatic PCE enhancement of 34% compared with the control devices
      with the same thickness.

PMID- 30240227
TI  - Kinetic Insights into Marangoni Effect-Assisted Preparation of Ultrathin Hydrogel
      Films.
AB  - In a previous work ( ACS Appl. Mater. Interfaces 2017, 9, 34349-34355), a facile
      approach was reported to prepare thin hydrogel films based on the Marangoni
      effect. After dripping onto a water surface, a drop of ethanol solution of
      poly(stearyl acrylate- co-acrylic acid) [P(SA- co-AAc)] spread quickly to form a
      thin film. The solvent exchange from ethanol to water led to the gelation of
      polymer solution which turned into a hydrogel film. Here, we investigate the
      scenario and seek for the governing kinetics of the Marangoni effect-assisted
      preparation of hydrogel films. By incorporating aggregation-induced emission
      fluorogens into the P(SA- co-AAc) solution, so that fluorescence appears at the
      gel state, we found that the spreading usually completed before the full gelation
      of the entire film. The spreading and formation of the gel films were influenced
      by the molar fraction of SA, f, and the polymer concentration of ethanol
      solution, CP. The spreading was blocked when CP was too high, whereas the film
      was fragmented into small pieces when CP was too low. At an intermediate CP,
      uniform hydrogel films were obtained. Steady spreading at a constant speed was
      observed during the processes which yielded uniform hydrogel films. Both CP and f
      influenced the spreading process by tuning the surface tension of the ethanol
      solution and the viscoelasticity of the gelated film, as suggested by our
      theoretical model. This work provided kinetic insights into the Marangoni
      phenomena of viscous polymer solutions. The strategy and principle should be
      applicable to other systems on preparing thin supramolecular gel films with
      versatile functions.

PMID- 30240228
TI  - Fluorinated Oligoethylenimine Nanoassemblies for Efficient siRNA-Mediated Gene
      Silencing in Serum-Containing Media by Effective Endosomal Escape.
AB  - Efficient small interfering RNA (siRNA) delivery in the presence of serum is of
      crucial importance for effective gene therapy. Fluorinated vectors are considered
      to be attractive candidates for siRNA-mediated gene therapy because of their
      delivery efficacy in serum-containing media. However, the mechanisms driving the
      superior gene transfection behavior of fluorinated vectors are still not well
      understood, and comprehensive investigations are warranted. Herein, we fabricated
      a library of perfluorooctanoyl fluoride-fluorinated (PFF-fluorinated)
      oligoethylenimines (f xOEIs, x is the PFF:OEI feeding ratio), which can readily
      form nanoassemblies (f xOEI NAs) capable of efficient siRNA delivery in cells
      cultured in medium both devoid of and supplemented with fetal bovine serum (FBS).
      The gene silencing test in serum-containing medium revealed that the
      f0.7OEI/siRNA NAs achieved a luciferase silencing of ~88.4% in Luc-HeLa cells
      cultured in FBS-containing medium, which was almost 2-fold greater than the
      silencing efficacy of siRNA delivered by the commercially available vector Lipo
      2000 (~48.8%). High levels of apolipoprotein B silencing were also achieved by
      f0.7OEI/siRNA NAs in vivo. For an assessment of the underlying mechanisms of the
      efficacy of gene silencing of fluorinated vectors, two alkylated OEIs, aOEI-C8
      and aOEI-C12, were fabricated as controls with similar molecular structure and
      hydrophobicity to that of f0.7OEI, respectively. In vitro investigations showed
      that the superior gene delivery exhibited by f0.7OEI NAs derived from the potent
      endosomal disruption capability of fluorinated vectors in the presence of serum,
      which was essentially attributed to the serum protein adsorption resistance of
      the f0.7OEI NAs. Therefore, this work provides an innovative approach to siRNA
      delivery as well as insights into fluorine-associated serum resistance.

PMID- 30240229
TI  - Counteracting Interfacial Energetics for Wetting of Hydrophobic Surfaces in the
      Presence of Surfactants.
AB  - Surface active agents (surfactants) are commonly used to improve the wetting of
      aqueous solutions on hydrophobic surfaces. The improved wettability is usually
      quantified as a decrease of the contact angle theta of a droplet on the surface,
      where the contact angle theta is given by the three surface tensions involved.
      Surfactants are known to lower the liquid-vapor surface tension, but what they do
      to the two other surface tensions is less clear. We propose an improved Zisman
      method for quantifying the wetting behavior of surfactants at the solid surface.
      This allows us to show that a number of very common surfactants do not change the
      wettability of the solid: they give the same contact angle as a simple liquid
      with the same liquid-vapor surface tension. Surface-specific sum-frequency
      generation spectroscopy shows that nonetheless surfactants are present at the
      solid surface. The surfactants therefore change the solid-liquid and solid-vapor
      surface tensions by the same amount, leading to an unchanged contact angle.

PMID- 30240230
TI  - Dirac-Weyl Semimetal: Coexistence of Dirac and Weyl Fermions in Polar Hexagonal
      ABC Crystals.
AB  - We propose that the noncentrosymmetric LiGaGe-type hexagonal ABC crystal SrHgPb
      realizes a new type of topological semimetal that hosts both Dirac and Weyl
      points in momentum space. The symmetry-protected Dirac points arise due to a band
      inversion and are located on the sixfold rotation z axis, whereas the six pairs
      of Weyl points related by sixfold symmetry are located on the perpendicular
      k_{z}=0 plane. By studying the electronic structure as a function of the buckling
      of the HgPb layer, which is the origin of inversion symmetry breaking, we
      establish that the coexistence of Dirac and Weyl fermions defines a phase
      separating two topologically distinct Dirac semimetals. These two Dirac
      semimetals are distinguished by the Z_{2} index of the k_{z}=0 plane and the
      corresponding presence or absence of 2D Dirac fermions on side surfaces. We
      formalize our first-principles calculations by deriving and studying a low-energy
      model Hamiltonian describing the Dirac-Weyl semimetal phase. We conclude by
      proposing several other materials in the noncentrosymmetric ABC material class,
      in particular SrHgSn and CaHgSn, as candidates for realizing the Dirac-Weyl
      semimetal.

PMID- 30240231
TI  - Imaging the Zigzag Wigner Crystal in Confinement-Tunable Quantum Wires.
AB  - The existence of Wigner crystallization, one of the most significant hallmarks of
      strong electron correlations, has to date only been definitively observed in two
      dimensional systems. In one-dimensional (1D) quantum wires Wigner crystals
      correspond to regularly spaced electrons; however, weakening the confinement and
      allowing the electrons to relax in a second dimension is predicted to lead to the
      formation of a new ground state constituting a zigzag chain with nontrivial spin
      phases and properties. Here we report the observation of such zigzag Wigner
      crystals by use of on-chip charge and spin detectors employing electron focusing
      to image the charge density distribution and probe their spin properties. This
      experiment demonstrates both the structural and spin phase diagrams of the 1D
      Wigner crystallization. The existence of zigzag spin chains and phases which can
      be electrically controlled in semiconductor systems may open avenues for
      experimental studies of Wigner crystals and their technological applications in
      spintronics and quantum information.

PMID- 30240233
TI  - Acoustothermal Atomization of Water Nanofilms.
AB  - We report nonequilibrium molecular simulations of the vibration-induced heating
      of nanoscale-thick water layers on a metal substrate. In addition to
      experimentally confirmed acoustothermal evaporation, we observe hitherto unmapped
      nucleate and film boiling regimes, accompanied by the generation of unprecedented
      heat fluxes [~O(10^{9})  W/m^{2}]. We develop a universal scaling parameter to
      classify the heat-transfer regimes and to predict the thickness of the residual
      nonevaporating liquid layer. The results find broad application to systems
      involving drying, coatings, and sprays.

PMID- 30240232
TI  - Measurement of the Dynamical Structure Factor of a 1D Interacting Fermi Gas.
AB  - We present measurements of the dynamical structure factor S(q,omega) of an
      interacting one-dimensional Fermi gas for small excitation energies. We use the
      two lowest hyperfine levels of the ^{6}Li atom to form a pseudospin-1/2 system
      whose s-wave interactions are tunable via a Feshbach resonance. The atoms are
      confined to one dimension by a two-dimensional optical lattice. Bragg
      spectroscopy is used to measure a response of the gas to density ("charge") mode
      excitations at a momentum q and frequency omega, as a function of the interaction
      strength. The spectrum is obtained by varying omega, while the angle between two
      laser beams determines q, which is fixed to be less than the Fermi momentum
      k_{F}. The measurements agree well with Tomonaga-Luttinger theory.

PMID- 30240234
TI  - Defect Unbinding in Active Nematics.
AB  - We formulate the statistical dynamics of topological defects in the active
      nematic phase, formed in two dimensions by a collection of self-driven particles
      on a substrate. An important consequence of the nonequilibrium drive is the
      spontaneous motility of strength +1/2 disclinations. Starting from the
      hydrodynamic equations of active nematics, we derive an interacting particle
      description of defects that includes active torques. We show that activity,
      within perturbation theory, lowers the defect-unbinding transition temperature,
      determining a critical line in the temperature-activity plane that separates the
      quasi-long-range ordered (nematic) and disordered (isotropic) phases. Below a
      critical activity, defects remain bound as rotational noise decorrelates the
      directed dynamics of +1/2 defects, stabilizing the quasi-long-range ordered
      nematic state. This activity threshold vanishes at low temperature, leading to a
      reentrant transition. At large enough activity, active forces always exceed
      thermal ones and the perturbative result fails, suggesting that in this regime
      activity will always disorder the system. Crucially, rotational diffusion being a
      two-dimensional phenomenon, defect unbinding cannot be described by a simplified
      one-dimensional model.

PMID- 30240235
TI  - Critical Level Crossings and Gapless Spin Liquid in the Square-Lattice Spin-1/2
      J_{1}-J_{2} Heisenberg Antiferromagnet.
AB  - We use the density matrix renormalization group method to calculate several
      energy eigenvalues of the frustrated S=1/2 square-lattice J_{1}-J_{2} Heisenberg
      model on 2L*L cylinders with L<=10. We identify excited-level crossings versus
      the coupling ratio g=J_{2}/J_{1} and study their drifts with the system size L.
      The lowest singlet-triplet and singlet-quintuplet crossings converge rapidly
      (with corrections ?L^{-2}) to different g values, and we argue that these
      correspond to ground-state transitions between the Neel antiferromagnet and a
      gapless spin liquid, at g_{c1}~0.46, and between the spin liquid and a valence
      bond solid at g_{c2}~0.52. Previous studies of order parameters were not able to
      positively discriminate between an extended spin liquid phase and a critical
      point. We expect level-crossing analysis to be a generically powerful tool in
      density matrix renormalization group studies of quantum phase transitions.

PMID- 30240236
TI  - Experimental Observation of Current Reversal in a Rocking Brownian Motor.
AB  - A reversal of the particle current in overdamped rocking Brownian motors was
      predicted more than 20 years ago; however, an experimental verification and a
      deeper insight into this noise-driven mechanism remained elusive. Here, we
      investigate the high-frequency behavior of a rocking Brownian motor for 60 nm
      gold spheres based on electrostatic interaction in a 3D-shaped nanofluidic slit
      and electro-osmotic forcing of the particles. We measure the particle probability
      density in situ with 10 nm spatial and 250  MUs temporal resolution and compare
      it with theory. At a driving frequency of 250 Hz, we observe a current reversal
      that can be traced to the asymmetric and increasingly static probability density
      at high frequencies.

PMID- 30240237
TI  - Violation of the Harris-Barghathi-Vojta Criterion.
AB  - In 1974, Harris proposed his celebrated criterion: Continuous phase transitions
      in d-dimensional systems are stable against quenched spatial randomness whenever
      dnu>2, where nu is the clean critical exponent of the correlation length. Forty
      years later, motivated by violations of the Harris criterion for certain lattices
      such as Voronoi-Delaunay triangulations of random point clouds, Barghathi and
      Vojta put forth a modified criterion for topologically disordered systems: anu>1,
      where a is the disorder decay exponent, which measures how fast coordination
      number fluctuations decay with increasing length scale. Here we present a
      topologically disordered lattice with coordination number fluctuations that decay
      as slowly as those of conventional uncorrelated randomness, but for which the
      clean universal behavior is preserved, hence violating even the modified
      criterion.

PMID- 30240238
TI  - Floquet Engineering of Multiorbital Mott Insulators: Applications to Orthorhombic
      Titanates.
AB  - We consider driving multiorbital Mott insulators using laser radiation. We derive
      general expressions for periodically driven spin-orbital models using time
      dependent perturbation theory in the strong interaction limit. We show that the
      effective exchange interactions of the Floquet spin-orbital Hamiltonian are
      highly tunable via variations of the frequency, amplitude, and polarization of
      the laser. We also take the effect of a finite bandwidth of excitations into
      account and study possible heating effects. We further apply our formalism to
      orthorhombic titanates YTiO_{3} and LaTiO_{3} based on first-principles
      calculations, and we find that the spin exchange interactions in these compounds
      can be engineered to a large extent by tuning the frequency and electric-field
      amplitude of the laser.

PMID- 30240239
TI  - Uncovering the Mechanism of the Impurity-Selective Mott Transition in
      Paramagnetic V_{2}O_{3}.
AB  - While the phase diagrams of the one- and multiorbital Hubbard model have been
      well studied, the physics of real Mott insulators is often much richer, material
      dependent, and poorly understood. In the prototype Mott insulator V_{2}O_{3},
      chemical pressure was initially believed to explain why the paramagnetic-metal to
      antiferromagnetic-insulator transition temperature is lowered by Ti doping while
      Cr doping strengthens correlations, eventually rendering the high-temperature
      phase paramagnetic insulating. However, this scenario has been recently shown
      both experimentally and theoretically to be untenable. Based on full structural
      optimization, we demonstrate via the charge self-consistent combination of
      density functional theory and dynamical mean-field theory that changes in the
      V_{2}O_{3} phase diagram are driven by defect-induced local symmetry breakings
      resulting from dramatically different couplings of Cr and Ti dopants to the host
      system. This finding emphasizes the high sensitivity of the Mott metal-insulator
      transition to the local environment and the importance of accurately accounting
      for the one-electron Hamiltonian, since correlations crucially respond to it.

PMID- 30240240
TI  - Loops in Anti-de Sitter Space.
AB  - We obtain analytic results for the four-point amplitude, at one loop, of an
      interacting scalar field theory in four-dimensional, Euclidean anti-de Sitter
      space without exerting any conformal field theory knowledge. For the two-point
      function, we provide analytic expressions up to two loops. In addition, we argue
      that the critical exponents of correlation functions near the conformal boundary
      of anti-de Sitter space provide the necessary data for the renormalization
      conditions, thus replacing the usual on-shell condition.

PMID- 30240241
TI  - Vesignieite: An S=1/2 Kagome Antiferromagnet with Dominant Third-Neighbor
      Exchange.
AB  - The spin-1/2 kagome antiferromagnet is an archetypal frustrated system predicted
      to host a variety of exotic magnetic states. We show using neutron scattering
      measurements that deuterated vesignieite BaCu_{3}V_{2}O_{8}(OD)_{2}, a fully
      stoichiometric S=1/2 kagome magnet with <1% lattice distortion, orders
      magnetically at T_{N}=9  K into a multi-k coplanar variant of the predicted
      triple-k octahedral structure. We find that this structure is stabilized by a
      dominant antiferromagnetic third-neighbor exchange J_{3} with minor first- or
      second-neighbor exchanges. The spin-wave spectrum is well described by a J_{3}
      only model including a tiny symmetric exchange anisotropy.

PMID- 30240242
TI  - Antisite Pairs Suppress the Thermal Conductivity of BAs.
AB  - BAs was predicted to have an unusually high thermal conductivity with a room
      temperature value of 2000  W m^{-1} K^{-1}, comparable to that of diamond.
      However, the experimentally measured thermal conductivity of BAs single crystals
      is still lower than this value. To identify the origin of this large
      inconsistency, we investigate the lattice structure and potential defects in BAs
      single crystals at the atomic scale using aberration-corrected scanning
      transmission electron microscopy (STEM). Rather than finding a large
      concentration of As vacancies (V_{As}), as widely thought to dominate the thermal
      resistance in BAs, our STEM results show an enhanced intensity of some B columns
      and a reduced intensity of some As columns, suggesting the presence of antisite
      defects with As_{B} (As atom on a B site) and B_{As} (B atom on an As site).
      Additional calculations show that the antisite pair with As_{B} next to B_{As} is
      preferred energetically among the different types of point defects investigated
      and confirm that such defects lower the thermal conductivity for BAs. Using a
      concentration of 1.8(8)% (6.6+/-3.0*10^{20}  cm^{-3} in density) for the antisite
      pairs estimated from STEM images, the thermal conductivity is estimated to be 65
      100  W m^{-1} K^{-1}, in reasonable agreement with our measured value. Our study
      suggests that As_{B}-B_{As} antisite pairs are the primary lattice defects
      suppressing thermal conductivity of BAs. Possible approaches are proposed for the
      growth of high-quality crystals or films with high thermal conductivity.
      Employing a combination of state-of-the-art synthesis, STEM characterization,
      theory, and physical insight, this work models a path toward identifying and
      understanding defect-limited material functionality.

PMID- 30240243
TI  - Observation of Three-Body Correlations for Photons Coupled to a Rydberg
      Superatom.
AB  - We report on the experimental observation of nontrivial three-photon correlations
      imprinted onto initially uncorrelated photons through an interaction with a
      single Rydberg superatom. Exploiting the Rydberg blockade mechanism, we turn a
      cold atomic cloud into a single effective emitter with collectively enhanced
      coupling to a focused photonic mode which gives rise to clear signatures in the
      connected part of the three-body correlation function of the outgoing photons. We
      show that our results are in good agreement with a quantitative model for a
      single, strongly coupled Rydberg superatom. Furthermore, we present an idealized
      but exactly solvable model of a single two-level system coupled to a photonic
      mode, which allows for an interpretation of our experimental observations in
      terms of bound states and scattering states.

PMID- 30240244
TI  - Information Thermodynamics of Turing Patterns.
AB  - We set up a rigorous thermodynamic description of reaction-diffusion systems
      driven out of equilibrium by time-dependent space-distributed chemostats.
      Building on the assumption of local equilibrium, nonequilibrium thermodynamic
      potentials are constructed exploiting the symmetries of the chemical network
      topology. It is shown that the canonical (resp. semigrand canonical)
      nonequilibrium free energy works as a Lyapunov function in the relaxation to
      equilibrium of a closed (resp. open) system, and its variation provides the
      minimum amount of work needed to manipulate the species concentrations. The
      theory is used to study analytically the Turing pattern formation in a
      prototypical reaction-diffusion system, the one-dimensional Brusselator model,
      and to classify it as a genuine thermodynamic nonequilibrium phase transition.

PMID- 30240245
TI  - Intrinsic Pink-Noise Multidecadal Global Climate Dynamics Mode.
AB  - Understanding multidecadal variability is an essential goal of climate dynamics.
      For example, the recent phenomenon referred to as the "global warming hiatus" may
      reflect a coupling to an intrinsic, preindustrial, multidecadal variability
      process. Here, using a multifractal time-series method, we demonstrate that 42
      data sets of 79 proxies with global coverage exhibit pink-noise characteristics
      on multidecadal timescales. To quantify the persistence of this behavior, we
      examine high-resolution ice core and speleothem data to find pink noise in both
      pre- and postindustrial periods. We examine the spatial structure with an
      empirical orthogonal function analysis of the monthly averaged surface
      temperature from 1901 to 2012. The first mode clearly shows the distribution of
      ocean heat flux sinks located in the eastern Pacific and the Southern Ocean and
      has pink-noise characteristics on a multidecadal timescale. We hypothesize that
      this pink-noise multidecadal spatial mode may resonate with externally driven
      greenhouse gas forcing, driving large-scale climate processes.

PMID- 30240246
TI  - Conversion Rules for Weyl Points and Nodal Lines in Topological Media.
AB  - According to a widely held paradigm, a pair of Weyl points with opposite
      chirality mutually annihilate when brought together. In contrast, we show that
      such a process is strictly forbidden for Weyl points related by a mirror
      symmetry, provided that an effective two-band description exists in terms of
      orbitals with opposite mirror eigenvalue. Instead, such a pair of Weyl points
      convert into a nodal loop inside a symmetric plane upon the collision. Similar
      constraints are identified for systems with multiple mirrors, facilitating
      previously unreported nodal-line and nodal-chain semimetals that exhibit both
      Fermi-arc and drumhead surface states. We further find that Weyl points in
      systems symmetric under a pi rotation composed with time reversal are
      characterized by an additional integer charge that we call helicity. A pair of
      Weyl points with opposite chirality can annihilate only if their helicities also
      cancel out. We base our predictions on topological crystalline invariants derived
      from relative homotopy theory, and we test our predictions on simple tight
      binding models. The outlined homotopy description can be directly generalized to
      systems with multiple bands and other choices of symmetry.

PMID- 30240247
TI  - Transition from Continuous to Discontinuous Shear Thickening: An Excluded-Volume
      Effect.
AB  - In this Letter, we present a new mechanism under the action of which a shear
      thickening suspension transitions from a continuous to a discontinuous regime.
      This transition occurs by adding high concentrations of large spheres to a
      continuous shear thickening suspension. We show that the solid volume fraction of
      the interstitial shear thickening matrix is locally enhanced due to the presence
      of large particles and the excluded-volume shells surrounding the large
      particles, thus leading to a continuous to discontinuous shear thickening
      transition at the local scale.

PMID- 30240249
TI  - Violating the Energy-Momentum Proportionality of Photonic Crystals in the Low
      Frequency Limit.
AB  - We theoretically show that the frequency and momentum of a photon are not
      necessarily proportional to one another at low frequencies in photonic crystals
      comprising materials with positive- and negative-valued material properties. We
      rigorously determine closed-form conditions for the light cone to emanate from
      points other than the origin of k space, ultimately decoupling the first band
      from the origin and demonstrating light propagation at zero energy with nonzero
      crystal momentum. We also numerically show that first bands can originate from an
      arbitrary Bloch coordinate as well as from multiple coordinates simultaneously.

PMID- 30240248
TI  - From Calcium to Cadmium: Testing the Pairing Functional through Charge Radii
      Measurements of ^{100-130}Cd.
AB  - Differences in mean-square nuclear charge radii of ^{100-130}Cd are extracted
      from high-resolution collinear laser spectroscopy of the 5s ^{2}S_{1/2}->5p
      ^{2}P_{3/2} transition of the ion and from the 5s5p ^{3}P_{2}->5s6s ^{3}S_{1}
      transition in atomic Cd. The radii show a smooth parabolic behavior on top of a
      linear trend and a regular odd-even staggering across the almost complete sdgh
      shell. They serve as a first test for a recently established new Fayans
      functional and show a remarkably good agreement in the trend as well as in the
      total nuclear charge radius.

PMID- 30240250
TI  - Electron Trapping from Interactions between Laser-Driven Relativistic Plasma
      Waves.
AB  - Interactions of large-amplitude relativistic plasma waves were investigated
      experimentally by propagating two synchronized ultraintense femtosecond laser
      pulses in plasma at oblique crossing angles to each other. The electrostatic and
      electromagnetic fields of the colliding waves acted to preaccelerate and trap
      electrons via previously predicted, but untested injection mechanisms of
      ponderomotive drift and wake-wake interference. High-quality energetic electron
      beams were produced, also revealing valuable new information about plasma-wave
      dynamics.

PMID- 30240251
TI  - Attosecond Time Delay of Retrapped Resonant Ionization.
AB  - A recent ultrafast pump-probe technique has allowed measurement of time delays
      during photoemission in a variety of systems ranging from atoms and molecules to
      solids with unprecedented temporal resolution. However, identifying the
      underlying physics is still a challenge especially in complicated multichannel
      above-threshold ionization (ATI) experiments. Here we demonstrate that the time
      delays of different ionization pathways in ATI can be clearly resolved and
      extracted with a semiclassical statistical method. The remarkable phase shift of
      near threshold photoelectrons can be attributed to a temporary retrapping of a
      photoelectron by the atomic potential in a quasibound state after emerging in the
      continuum state. This continuum-bound-continuum scattering manifests as a new
      resonant effect in strong-field photoemission. Our results unify the seemingly
      opposing quantum Eisenbud-Wigner-Smith time delay and classical Coulomb-induced
      time delay by highlighting the same physical picture, which holds promise for an
      intuitive interpretation of time-resolved fundamental electronic processes in
      strong-field experiments and epistemological reexamination of the quantum
      classical correspondence.

PMID- 30240252
TI  - Spontaneous Exact Spin-Wave Fractals in Magnonic Crystals.
AB  - Exact fractals of nonlinear waves that rely on strong dispersion and nonlinearity
      and arise spontaneously out of magnetic media were observed for the first time.
      The experiments make use of a microwave to excite a spin wave in a quasi-one
      dimensional magnonic crystal. When the power of the input microwave (P_{in}) is
      low, the output signal has a power-frequency spectrum that consists of a single
      peak. When P_{in} is increased to a certain level, new side modes are generated
      through modulational instability, resulting in a comblike frequency spectrum.
      With a further increase in P_{in}, each peak in the frequency comb can evolve
      into its own finer comb through the modulational instability. As P_{in} is
      increased further, one can observe yet another set of finer frequency combs. Such
      a frequency-domain fractal manifests itself as multiple layers of amplitude
      modulation in the time-domain signal.

PMID- 30240253
TI  - Short-Lived Radioisotope ^{98}Tc Synthesized by the Supernova Neutrino Process.
AB  - The isotope ^{98}Tc decays to ^{98}Ru with a half-life of 4.2*10^{6}   yr and
      could have been present in the early Solar System. In this Letter, we report on
      the first calculations of the production of ^{98}Tc by neutrino-induced reactions
      in core-collapse supernovae (the nu process). Our predicted ^{98}Tc abundance at
      the time of solar system formation is not much lower than the current measured
      upper limit raising the possibility for its detection in the not too distant
      future. We show that, if the initial abundance were to be precisely measured, the
      ^{98}Tc nuclear cosmochronometer could be used to evaluate a much more precise
      value of the duration time from the last core-collapse supernova to the formation
      of the solar system. Moreover, a unique and novel feature of the ^{98}Tc nu
      process nucleosynthesis is the large contribution (~20%) from charged current
      reactions with electron antineutrinos. This means that ^{98}Tc becomes a unique
      new nu-process probe of the temperature of the electron antineutrinos.

PMID- 30240254
TI  - Canceling the U(1) Anomaly in the S Matrix of N=4 Supergravity.
AB  - N=4 supergravity is understood to contain a U(1) anomaly which manifests itself
      via the nonvanishing of loop-level scattering amplitudes that violate a tree
      level charge conservation rule. In this Letter we provide detailed evidence that
      at one loop such anomalous amplitudes can be set to zero by the addition of a
      finite local counterterm. We show that the same counterterm also cancels
      evanescent contributions that play an important role in the analysis of
      ultraviolet divergences in dimensionally regularized gravity. These cancellations
      call for a reanalysis of the four-loop ultraviolet divergences previously found
      in this theory without the addition of such counterterms.

PMID- 30240255
TI  - Primordial Non-Gaussianities and Zero-Bias Tracers of the Large-Scale Structure.
AB  - We develop a new method to constrain primordial non-Gaussianities of the local
      kind using unclustered tracers of the large scale structure. We show that, in the
      limit of low noise, zero bias tracers yield large improvement over standard
      methods, mostly due to vanishing sampling variance. We propose a simple technique
      to construct such a tracer, using environmental information obtained from the
      original sample and validate our method with N-body simulations. Our results
      indicate that sigma_{f_{NL}^{loc}}?1 can be reached using only information on a
      single tracer of sufficiently high number density.

PMID- 30240256
TI  - Concentrators for Water Waves.
AB  - By introducing concepts from transformation optics to the manipulation of water
      waves, we design and experimentally demonstrate two annular devices for
      concentrating waves, which employ gradient depth profiles based on Fabry-Perot
      resonances. Our measurements and numerical simulations confirm the concentrating
      effect of the annular devices and show that they are effectively invisible to the
      water waves. We show that transformation optics is thus an effective framework
      for designing devices to improve the efficiency of wave energy collection, and we
      expect potential applications in coastline ocean engineering.

PMID- 30240257
TI  - Peregrine Solitons Beyond the Threefold Limit and Their Two-Soliton Interactions.
AB  - Within the coupled Fokas-Lenells equations framework, we show explicitly that, in
      contrast to the expected threefold-amplitude magnification, Peregrine solitons
      can reach a peak amplitude as high as 5 times the background level. Besides, the
      interaction of two such anomalous Peregrine solitons can generate a spikelike
      rogue wave of extremely high peak amplitude, depending on the parameters used. We
      numerically confirm that the Peregrine soliton beyond the threefold limit can be
      reproduced from either a deterministic initial profile or a chaotic background
      field, hence anticipating the feasibility of its experimental observation.

PMID- 30240258
TI  - Dynamic Vorticity Banding in Discontinuously Shear Thickening Suspensions.
AB  - It has recently been argued that steady-state vorticity bands cannot arise in
      shear thickening suspensions because the normal stress imbalance across the
      interface between the bands will set up particle migrations. In this Letter, we
      develop a simple continuum model that couples shear thickening to particle
      migration. We show by linear stability analysis that homogeneous flow is unstable
      towards vorticity banding, as expected, in the regime of negative constitutive
      slope. In full nonlinear computations, we show, however, that the resulting
      vorticity bands are unsteady, with spatiotemporal patterns governed by stress
      concentration coupling. We furthermore show that these dynamical bands also arise
      in direct particle simulations, in good agreement with the continuum model.

PMID- 30240259
TI  - Noise-Induced Backscattering in a Quantum Spin Hall Edge.
AB  - Time-reversal symmetry suppresses electron backscattering in a quantum-spin-Hall
      edge, yielding quantized conductance at zero temperature. Understanding the
      dominant corrections in finite-temperature experiments remains an unsettled
      issue. We study a novel mechanism for conductance suppression: backscattering
      caused by incoherent electromagnetic noise. Specifically, we show that an
      electric potential fluctuating randomly in time can backscatter electrons
      inelastically without constraints faced by electron-electron interactions. We
      quantify noise-induced corrections to the dc conductance in various regimes and
      propose an experiment to test this scenario.

PMID- 30240260
TI  - Experimental Observation of Topologically Protected Bound States with Vanishing
      Chern Numbers in a Two-Dimensional Quantum Walk.
AB  - Quantum walks (QWs) provide a powerful tool as a quantum simulator to study and
      understand topological phases. Using such a quantum simulator, some topological
      phenomena have been discussed. However, all the experimental observations on the
      topological phenomena in QWs have been restricted to evolution in one dimension
      (1D) so far. The existing 2D experimental platforms cannot be applied to study
      topological phenomena due to lack of full control in the position space. Thus,
      some interesting topological phenomena in the 2D QW that do not exist in the 1D
      case, e.g., the edge-state-enhanced transport, have not been demonstrated
      experimentally. Here we report the experimental realization of 2D QW using
      spatial positions and orbital angular momentum of light. Based on our constructed
      experimental platform, we have observed 2D topological bound states with
      vanishing Chern numbers and confirmed the robustness of these bound states with
      respect to perturbations and disorder, which go beyond what has been known in
      static systems and are unique to periodically driven systems. Our studies not
      only represent an important advance in the study of topological phases, but also
      open up an avenue to explore topological properties in multidimensional QWs.

PMID- 30240261
TI  - Clusters of Cavity Solitons Bounded by Conical Radiation.
AB  - We introduce a new class of self-sustained states, which may exist as single
      solitons or form multisoliton clusters, in driven passive cylindrical
      microresonators. Remarkably, such states are stabilized by the radiation they
      emit, which strongly breaks spatial symmetry and leads to the appearance of long
      polychromatic conical tails. The latter induce long-range soliton interactions
      that make possible the formation of clusters, which can be stable if their
      spatial arrangement is noncollinear with the soliton rotation direction in the
      microcavity. The clusters are intrinsically two dimensional and, also, spatially
      rich. The mechanism behind the formation of the clusters is explained using
      soliton clustering theory. Our results bring fundamental understanding of a new
      class of multidimensional cavity solitons and may lead to the development of
      monolithic multisoliton sources.

PMID- 30240262
TI  - Resolving the Lambda Hypernuclear Overbinding Problem in Pionless Effective Field
      Theory.
AB  - We address the Lambda hypernuclear "overbinding problem" in light hypernuclei
      which stands for a 1-3 MeV excessive Lambda separation energy calculated in
      _{Lambda}^{5}He. This problem arises in most few-body calculations that reproduce
      ground-state Lambda separation energies in the lighter Lambda hypernuclei within
      various hyperon-nucleon interaction models. Recent pionless effective field
      theory (piEFT) nuclear few-body calculations are extended in this work to Lambda
      hypernuclei. At leading order, the LambdaN low-energy constants are associated
      with LambdaN scattering lengths, and the LambdaNN low-energy constants are fitted
      to Lambda separation energies (B_{Lambda}^{exp}) for A<=4. The resulting piEFT
      interaction reproduces in few-body stochastic variational method calculations the
      reported value B_{Lambda}^{exp}(_{Lambda}^{5}He)=3.12+/-0.02  MeV within a
      fraction of MeV over a broad range of piEFT cutoff parameters. Possible
      consequences and extensions to heavier hypernuclei and to neutron-star matter are
      discussed.

PMID- 30240263
TI  - Black Hole Disks in Galactic Nuclei.
AB  - Gravitational torques among objects orbiting a supermassive black hole drive the
      rapid reorientation of orbital planes in nuclear star clusters (NSCs), a process
      known as vector resonant relaxation. In this Letter, we determine the statistical
      equilibrium of systems with a distribution of masses, semimajor axes, and
      eccentricities. We average the interaction over the apsidal precession time and
      construct a Monte Carlo Markov chain method to sample the microcanonical ensemble
      of the NSC. We examine the case of NSCs formed by 16 episodes of star formation
      or globular cluster infall. We find that the massive stars and stellar mass black
      holes form a warped disk, while low mass stars resemble a spherical distribution
      with a possible net rotation. This explains the origin of the clockwise disk in
      the Galactic center and predicts a population of black holes (BHs) embedded
      within this structure. The rate of mergers among massive stars, tidal disruption
      events of massive stars by BHs, and BH-BH mergers are highly increased in such
      disks. The first two may explain the origin of the observed G1 and G2 clouds, the
      latter may be important for gravitational wave detections with LIGO and VIRGO.
      More generally, black holes are expected to settle in disks in all dense
      spherical stellar systems assembled by mergers of smaller systems including
      globular clusters.

PMID- 30240264
TI  - Tunable Orbital Angular Momentum Radiation from Angular-Momentum-Biased
      Microcavities.
AB  - Lasers and light emitters do not typically radiate fields with orbital angular
      momentum (OAM). Here we show that a suitable scheme of spatiotemporal modulation
      of a microring cavity laser can impart a synthetic angular momentum, resulting in
      beams with well-defined OAM. The phenomenon relies on a traveling wave modulation
      of the refractive index of the microring, which breaks the degeneracy of
      oppositely oriented whispering gallery modes. In parallel, a static structural
      grating on the periphery of the microring enables efficient vertical radiation.
      The proposed structure is inherently tunable and can also emit fields with zero
      net OAM while retaining toroidal energy distributions similar to the effect of an
      axicon lens.

PMID- 30240265
TI  - Disorder-Driven Transition from s_{+/-} to s_{++} Superconducting Order Parameter
      in Proton Irradiated Ba(Fe_{1-x}Rh_{x})_{2}As_{2} Single Crystals.
AB  - Microwave measurements of the London penetration depth and critical temperature
      T_{c} were used to show evidence of a disordered-driven transition from s_{+/-}
      to s_{++} order parameter symmetry in optimally doped Ba(Fe_{1
      x}Rh_{x})_{2}As_{2} single crystals, where disorder was induced by means of 3.5
      MeV proton irradiation. Signatures of such a transition, as theoretically
      predicted [V. D. Efremov et al., Phys. Rev. B 84, 180512(R) (2011)PRBMDO1098
      012110.1103/PhysRevB.84.180512], are found as a drop in the low-temperature
      values of the London penetration depth and a virtually disorder-independent
      superconducting T_{c}. We show how these experimental observations can be
      described by multiband Eliashberg calculations in which the effect of disorder is
      accounted for in a suitable way. To this aim, an effective two-band approach is
      adopted, allowing us to treat disorder in a range between the Born approximation
      and the unitary limit.

PMID- 30240266
TI  - Vacuum Selection from Cosmology on Networks of String Geometries.
AB  - We introduce network science as a framework for studying the string landscape.
      Two large networks of string geometries are constructed, where nodes are extra
      dimensional six-manifolds and edges represent topological transitions between
      them. We show that a standard bubble cosmology model on the networks has late
      time behavior determined by the largest eigenvector of -(L+D), where L and D are
      the Laplacian and degree matrices of the networks, which provides a dynamical
      mechanism for vacuum selection in the string landscape.

PMID- 30240267
TI  - Band Topology and Linking Structure of Nodal Line Semimetals with Z_{2} Monopole
      Charges.
AB  - We study the band topology and the associated linking structure of topological
      semimetals with nodal lines carrying Z_{2} monopole charges, which can be
      realized in three-dimensional systems invariant under the combination of
      inversion P and time reversal T when spin-orbit coupling is negligible. In
      contrast to the well-known PT-symmetric nodal lines protected only by the pi
      Berry phase, in which a single nodal line can exist, the nodal lines with Z_{2}
      monopole charges should always exist in pairs. We show that a pair of nodal lines
      with Z_{2} monopole charges is created by a double band inversion process and
      that the resulting nodal lines are always linked by another nodal line formed
      between the two topmost occupied bands. It is shown that both the linking
      structure and the Z_{2} monopole charge are the manifestation of the nontrivial
      band topology characterized by the second Stiefel-Whitney class, which can be
      read off from the Wilson loop spectrum. We show that the second Stiefel-Whitney
      class can serve as a well-defined topological invariant of a PT-invariant two
      dimensional insulator in the absence of Berry phase. Based on this, we propose
      that pair creation and annihilation of nodal lines with Z_{2} monopole charges
      can mediate a topological phase transition between a normal insulator and a three
      dimensional weak Stiefel-Whitney insulator. Moreover, using first-principles
      calculations, we predict ABC-stacked graphdiyne as a nodal line semimetal (NLSM)
      with Z_{2} monopole charges having the linking structure. Finally, we develop a
      formula for computing the second Stiefel-Whitney class based on parity
      eigenvalues at inversion-invariant momenta, which is used to prove the quantized
      bulk magnetoelectric response of NLSMs with Z_{2} monopole charges under a T
      breaking perturbation.

PMID- 30240268
TI  - Observation of Topologically Protected Edge States in a Photonic Two-Dimensional
      Quantum Walk.
AB  - Periodically driven systems have displayed a variety of fascinating phenomena
      without analogies in static systems, which enrich the classification of quantum
      phases of matter and stimulate a wide range of research interests. Here, we
      employ discrete-time quantum walks to investigate a nontrivial topological effect
      unique to a two-dimensional periodically driven system: chiral edge states can
      exist at the interface of Floquet insulators whose Chern numbers vanish. Thanks
      to a resource-saving and flexible fiber-loop architecture, we realize
      inhomogeneous two-dimensional quantum walks up to 25 steps, over an effective
      51*51 lattice with tunable local parameters. Spin-polarized chiral edge states
      are observed at the boundary of two distinct quantum walk domains. Our results
      contribute to establishing a well-controlled platform for exploring nontrivial
      topological phases.

PMID- 30240269
TI  - Directly Detecting Sub-GeV Dark Matter with Electrons from Nuclear Scattering.
AB  - Dark matter (DM) particles with mass in the sub-GeV range are an attractive
      alternative to heavier weakly interacting massive particles, but direct detection
      of such light particles is challenging. If, however, DM-nucleus scattering leads
      to ionization of the recoiling atom, the resulting electron may be detected even
      if the nuclear recoil is unobservable. We demonstrate that including this effect
      significantly enhances direct detection sensitivity to sub-GeV DM. Existing
      experiments set world-leading limits, and future experiments may probe the cross
      sections relevant for thermal freeze-out.

PMID- 30240270
TI  - Conclusive Experimental Demonstration of One-Way Einstein-Podolsky-Rosen
      Steering.
AB  - Einstein-Podolsky-Rosen steering is a quantum phenomenon wherein one party
      influences, or steers, the state of a distant party's particle beyond what could
      be achieved with a separable state, by making measurements on one-half of an
      entangled state. This type of quantum nonlocality stands out through its
      asymmetric setting and even allows for cases where one party can steer the other
      but where the reverse is not true. A series of experiments have demonstrated one
      way steering in the past, but all were based on significant limiting assumptions.
      These consisted either of restrictions on the type of allowed measurements or of
      assumptions about the quantum state at hand, by mapping to a specific family of
      states and analyzing the ideal target state rather than the real experimental
      state. Here, we present the first experimental demonstration of one-way steering
      free of such assumptions. We achieve this using a new sufficient condition for
      nonsteerability and, although not required by our analysis, using a novel source
      of extremely high-quality photonic Werner states.

PMID- 30240271
TI  - Spontaneous Scalarization of Charged Black Holes.
AB  - Extended scalar-tensor Gauss-Bonnet (ESTGB) gravity has been recently argued to
      exhibit spontaneous scalarization of vacuum black holes (BHs). A similar
      phenomenon can be expected in a larger class of models, which includes, e.g.,
      Einstein-Maxwell scalar (EMS) models, where spontaneous scalarization of
      electrovacuum BHs should occur. EMS models have no higher curvature corrections,
      a technical simplification over ESTGB models that allows us to investigate, fully
      nonlinearly, BH scalarization in two novel directions. First, numerical
      simulations in spherical symmetry show, dynamically, that Reissner-Nordstrom (RN)
      BHs evolve into a perturbatively stable scalarized BH. Second, we compute the
      nonspherical sector of static scalarized BH solutions bifurcating from the RN BH
      trunk. Scalarized BHs form an infinite (countable) number of branches and possess
      a large freedom in their multipole structure. Unlike the case of electrovacuum,
      the EMS model admits static, asymptotically flat, regular on and outside the
      horizon BHs without spherical symmetry and even without any spatial isometries,
      which are thermodynamically preferred over the electrovacuum state. We speculate
      on a possible dynamical role of these nonspherical scalarized BHs.

PMID- 30240273
TI  - Analytic Two-Loop Higgs Amplitudes in Effective Field Theory and the Maximal
      Transcendentality Principle.
AB  - We obtain, for the first time, the two-loop amplitudes for Higgs plus three
      gluons in Higgs effective field theory including dimension-seven operators. This
      provides the S-matrix elements for the top mass corrections for Higgs plus a jet
      production at LHC. The computation is based on the on-shell unitarity method
      combined with integration by parts reduction. We work in conventional dimensional
      regularization and obtain analytic expressions renormalized in the modified
      minimal subtraction scheme. The two-loop anomalous dimensions present operator
      mixing behavior. The infrared divergences agree with that predicted by Catani and
      the finite remainders take remarkably simple forms, where the maximally
      transcendental parts are identical to the corresponding results in N=4 super-Yang
      Mills theory. The parts of lower transcendentality turn out to be also largely
      determined by the N=4 results.

PMID- 30240274
TI  - Unconditional Steady-State Entanglement in Macroscopic Hybrid Systems by Coherent
      Noise Cancellation.
AB  - The generation of entanglement between disparate physical objects is a key
      ingredient in the field of quantum technologies, since they can have different
      functionalities in a quantum network. Here we propose and analyze a generic
      approach to steady-state entanglement generation between two oscillators with
      different temperatures and decoherence properties coupled in cascade to a common
      unidirectional light field. The scheme is based on a combination of coherent
      noise cancellation and dynamical cooling techniques for two oscillators with
      effective masses of opposite signs, such as quasispin and motional degrees of
      freedom, respectively. The interference effect provided by the cascaded setup can
      be tuned to implement additional noise cancellation leading to improved
      entanglement even in the presence of a hot thermal environment. The unconditional
      entanglement generation is advantageous since it provides a ready-to-use quantum
      resource. Remarkably, by comparing to the conditional entanglement achievable in
      the dynamically stable regime, we find our unconditional scheme to deliver a
      virtually identical performance when operated optimally.

PMID- 30240272
TI  - Control of H_{2} Dissociative Ionization in the Nonlinear Regime Using Vacuum
      Ultraviolet Free-Electron Laser Pulses.
AB  - The role of the nuclear degrees of freedom in nonlinear two-photon single
      ionization of H_{2} molecules interacting with short and intense vacuum
      ultraviolet pulses is investigated, both experimentally and theoretically, by
      selecting single resonant vibronic intermediate neutral states. This high
      selectivity relies on the narrow bandwidth and tunability of the pulses generated
      at the FERMI free-electron laser. A sustained enhancement of dissociative
      ionization, which even exceeds nondissociative ionization, is observed and
      controlled as one selects progressively higher vibronic states. With the help of
      ab initio calculations for increasing pulse durations, the photoelectron and ion
      energy spectra obtained with velocity map imaging allow us to identify new
      photoionization pathways. With pulses of the order of 100 fs, the experiment
      probes a timescale that lies between that of ultrafast dynamical processes and
      that of steady state excitations.

PMID- 30240275
TI  - Nasal High Flow Delivered within the Helmet: A New Non-Invasive Respiratory
      Support.

PMID- 30240276
TI  - Pulmonary Lymphatic Perfusion Syndrome.

PMID- 30240277
TI  - Critical appraisal of systematic reviews of executive function treatments in TBI.
AB  - OBJECTIVE: To appraise the quality of systematic reviews (SRs) and meta-analyses
      (MAs) that summarize the treatment literature for executive function (EF)
      impairments following traumatic brain injury (TBI). METHODS: We used five data
      sources (PubMed; PsycINFO; ANCDS.org; Cochrane Collaboration; American Speech
      Language-Hearing Association Compendium; Psychological Database for Brain
      Impairment Treatment Efficacy) and identified 19 reviews that met eligibility
      criteria (adults with TBI; behavioural treatments for EF impairments; no
      pharmacologic treatments). Two reviewers independently and reliably rated each
      paper using two appraisal tools (Critical Appraisal of Systematic Review or Meta
      Analysis and Evidence in Augmentative and Alternative Communication systematic
      review scale). RESULTS: Five MAs received highest ratings. Four SRs also
      addressed the majority of SR criteria. Reviews were better at addressing SR
      criteria as outcome measures across studies varied considerably, posing a
      challenge to quantitatively synthesize TBI outcomes. The strongest research
      evidence favours compensatory treatments that train individuals with TBI to use
      strategies to circumvent EF impairments in daily activities. Smaller effects are
      reported for direct training approaches. CONCLUSIONS: Researchers need to
      identify core outcome measures to facilitate future rigorous MAs of the EF
      rehabilitation literature. SRs/MAs need to be conducted with thorough methods
      that are reported with detail.

PMID- 30240279
TI  - Physiological Markers for ARDS: Let's Get More Efficient!

PMID- 30240278
TI  - Interleukin-9 Blockade Suppresses Silica-induced Lung Inflammation and Fibrosis
      in Mice.
AB  - Recapitulative animal models of idiopathic pulmonary fibrosis (IPF) and related
      diseases are lacking, which inhibits our ability to fully clarify the
      pathogenesis of these diseases. Although lung fibrosis in mouse models is often
      induced by bleomycin, silica-induced lung fibrosis is more sustainable and more
      progressive. Therefore, in this study, we sought to elucidate the mediator(s)
      responsible for the pathogenesis of lung fibrosis through the use of a mouse
      model of silica-induced lung fibrosis. With a single nasal administration of 16
      mg of silica, lung inflammation (assessed by elevated cellular components in the
      bronchoalveolar lavage fluids [BALFs]) and lung fibrosis (assessed by lung
      histology and lung hydroxyproline levels) were induced and sustained for as long
      as 24 weeks. Of the mediators measured in the BALFs, interleukin-9 (IL-9) was
      characteristically elevated gradually and peaked at 24 weeks after silica
      administration. Treatment of silica-challenged mice with anti-IL-9 neutralizing
      Ab inhibited lung fibrosis, as assessed by lung hydroxyproline level, and
      suppressed the levels of major mediators, including IL-1beta, IL-6, IL-12, CCL2,
      CXCL1, and tumor necrosis factor alpha in BALFs. Moreover, human lung specimens
      from IPF patients have shown high expression of IL-9 in alveolar macrophages, CD4
      positive cells, and receptors for IL-9 in airway epithelial cells. Collectively,
      these data suggest that IL-9 plays an important role in the pathogenesis of lung
      fibrosis in diseases such as IPF.

PMID- 30240280
TI  - Improving image quality with model-based iterative reconstruction at quarter of
      nominal dose in upper abdominal CT.
AB  - OBJECTIVE:: To evaluate the ability of a model-based iterative reconstruction
      (MBIR) for improving image quality in upper abdominal CT with quarter of the
      normal dose, in comparison with adaptive statistical iterative reconstruction
      (ASiR) at normal dose. METHODS:: 40 upper abdominal patients were randomly
      divided into two groups: normal-dose group (n = 20) with tube current modulation
      for noise index (NI) of 10 HU and 40% ASiR reconstruction; low-dose group (n =
      20) with NI = 20  HU in the delay phase and MBIR and 40%ASiR. Images in the delay
      phase were compared. The CT values and standard deviation (SD) values of the
      liver, spleen, pancreas, kidney, erector spine and fat were measured. Contrast
      noise-ratio (CNR = (CTtissue-CT fat)/SDfat) of each measured organ were
      calculated and compared with one-way ANOVA among the three reconstruction groups.
      The subjective image scores of the three groups were assessed blindly by two
      experienced physicians using a 5-point system and the score consistency was
      compared by the kappa test. RESULTS:: Dose reduction of 75 % was achieved for the
      low-dose scan. The subjective scores (95 % confidence intervals) of the three
      groups (NI 10-40 %  ASiR, NI 20-40%  ASiR and NI 20-MBIR) were 4.00 +/- 0.79
      (3.62-4.37), 3.35 +/- 0.58 (3.07-3.62) and 3.90 +/- 0.64 (3.60-4.19),
      respectively with no difference between the NI 10-40%  ASiR and NI20-MBIR groups
      and good consistency between reviewers (kappa = 0.726). MBIR had statistically
      lower SD values and higher contrast-to-noise ratio values in the liver, spleen,
      pancreas, kidney and erector spine than NI 10-40%  ASiR and NI 20-40%  ASiR (all
      p < 0.05). CONCLUSION:: At 75 % dose reduction, MBIR provides similar image
      quality compared to 40% ASiR at normal-dose. ADVANCES IN KNOWLEDGE:: MBIR
      provides good image quality at 25 % of the normal dose.

PMID- 30240281
TI  - Healthcare Utilization by Glaucoma Patients in a Team Care Model.
AB  - PURPOSE: To determine the effect of a glaucoma team care model on resource
      utilization and efficiency in glaucoma management. METHODS: Retrospective cohort
      study of 358 patients diagnosed and treated for glaucoma. Analysis included
      number of patient visits, diagnostic tests, and glaucoma procedures performed
      before (2005-2007) and after (2008-2010) implementation of a team care model in
      2008. Patients not involved in the model served as controls. RESULTS: Number of
      patient visits did not change significantly after model implementation (p > .05).
      Diagnostic tests significantly increased in comprehensive ophthalmologist and
      glaucoma subspecialist groups 25 months after diagnosis (p = .03 and p = .001).
      Procedures increased for glaucoma subspecialists but was not statistically
      significant (p = .06). Optometrists used billing codes with significantly lower
      reimbursement than other providers (p < .001). CONCLUSIONS: Team care model had
      neutral effect on patient visits and increased testing. Continued evaluation of
      this model is required to determine its effect on disease progression and
      outcomes.

PMID- 30240282
TI  - Psychedelics and music: neuroscience and therapeutic implications.
AB  - From the beginning of therapeutic research with psychedelics, music listening has
      been consistently used as a method to guide or support therapeutic experiences
      during the acute effects of psychedelic drugs. Recent findings point to the
      potential of music to support meaning-making, emotionality, and mental imagery
      after the administration of psychedelics, and suggest that music plays an
      important role in facilitating positive clinical outcomes of psychedelic therapy.
      This review explores the history of, contemporary research on, and future
      directions regarding the use of music in psychedelic research and therapy, and
      argues for more detailed and rigorous investigation of the contribution of music
      to the treatment of psychiatric disorders within the novel framework of
      psychedelic therapy.

PMID- 30240283
TI  - QSPR modelling of in vitro degradation half-life of acyl glucuronides.
AB  - Acyl glucuronidation is an important Phase II biotransformation, which is an
      efficient detoxification mechanism for the metabolism of carboxylic acid group
      containing drugs. However, the reactivity of acyl glucuronide (AG) metabolites
      associated with short half-lives may be an indication of idiosyncratic drug
      toxicity. The degradation half-lives of AGs elucidate several important reactions
      such as hydrolysis, acyl migration and covalent binding to proteins. Prediction
      of degradation half-life using computational methods is a promising alternative
      approach to costly and time-consuming experiments, enabling a priori evaluation
      of the properties of drug candidates during the drug design process. The main
      objective of the present study was to develop a linear model for the quantitative
      prediction of half-lives of acyl glucuronidated drug-like compounds. The proposed
      model revealed that the number of total quaternary carbons, the complexity of the
      ring in the compound, Sanderson electronegativities, and dipole moment of the
      compound are important molecular features in predicting the half-life of an AG.
      The rigorously validated model can contribute to a better understanding of
      molecular features of these drugs to predict degradation half-lives.

PMID- 30240284
TI  - A temporal transcriptome and methylome in human embryonic stem cell-derived
      cardiomyocytes identifies novel regulators of early cardiac development.
AB  - Stem cell-based cardiogenesis has become a powerful tool to enhance our
      understanding of cardiac development and test novel therapeutics for
      cardiovascular diseases. However, transcriptional and epigenetic regulation of
      multiple transitional stages from pluripotent cells to committed cardiomyocytes
      has not yet been fully characterized. To characterize how transcription factors,
      lincRNAs and DNA methylation change at temporal developmental stages, and
      identify potential novel regulators during cardiogenesis. We utilized a
      previously reported protocol that yields human cardiomyocytes (hCM) with more
      than 90% purity from human Embryonic Stem Cells (hESC). Leveraging the purity of
      cells resulting from this protocol, we systematically examined how gene
      expression and DNA methylation programs change at temporal developmental stages
      during cardiogenesis. Our results provide a comprehensive view of expression
      changes during cardiogenesis that extend previous studies, allowing us to
      identify key transcription factors as well as lincRNAs that are strongly
      associated with cardiac differentiation. Moreover, we incorporated a simple but
      powerful method to screen for novel regulators of cardiogenesis solely based on
      expression changes and found four novel cardiac-related transcription factors,
      i.e., SORBS2, MITF, DPF3, and ZNF436, which have no or few prior literature
      reports and we were able to validate using siRNA. Our strategy of identifying
      novel regulators of cardiogenesis can also be easily implemented in other stem
      cell-based systems. Our results provide a valuable resource for understanding
      cardiogenesis that extends previous findings by leveraging the purity of our cell
      lines, which allowed us to identify four novel cardiac-related regulators.

PMID- 30240285
TI  - Sex Differences in Pulmonary Responses to Ozone in Mice: Role of the Microbiome.
AB  - We have previously reported that the mouse gut microbiome contributes to
      pulmonary responses to ozone, a common asthma trigger, and that short chain fatty
      acids, end products of bacterial fermentation, likely contribute to this role of
      the microbiome. A growing body of evidence indicates sex-related differences in
      gut microbiota and that these differences can have important functional
      consequences. The purpose of this study was to determine whether there were sex
      related differences in the impact of the gut microbiota on pulmonary responses to
      ozone. After acute exposure to ozone, male mice developed greater airway
      hyperresponsiveness than female mice. This difference was abolished after
      antibiotic ablation of the gut microbiome. Moreover, weanling female pups housed
      in cages conditioned by adult male mice developed greater ozone-induced airway
      hyperresponsiveness than weanling female pups raised in cages conditioned by
      adult females. Finally, ad libitum oral administration via drinking water of the
      short chain fatty acid, propionate, resulted in augmented ozone-induced airway
      hyperresponsiveness in male but not in female mice. Overall, these data are
      consistent with the hypothesis that the microbiome contributes to sex differences
      in ozone-induced airway hyperresponsiveness, likely as a result of sex
      differences in the response to short chain fatty acids.

PMID- 30240287
TI  - The Young Child with Severe Obesity: Commentary on the Characteristics of a
      Vulnerable Population and a Framework for Treatment.

PMID- 30240288
TI  - Diagnostic Accuracy of Sex-Specific Chest CT Measurements Compared With Cardiac
      MRI Findings in the Assessment of Cardiac Chamber Enlargement.
AB  - OBJECTIVE: The purpose of this study was to establish sex-specific chest CT
      measurement thresholds for detection of cardiac chamber enlargement with cardiac
      MRI as the reference standard. MATERIALS AND METHODS: Consecutive patients who
      underwent contrast-enhanced chest CT (64- or 320-MDCT) and cardiac MRI within a 7
      day interval between August 2006 and August 2016 were included in this
      retrospective study (n = 217; 115 men, 102 women; mean age, 52.8 +/- 15.8 years).
      Measurements were performed on axial CT images to evaluate right atrial (RA),
      right ventricular (RV), left atrial (LA), and left ventricular (LV) chamber size.
      The presence of chamber enlargement (RAE, RVE, LAE, and LVE) was established with
      cardiac MRI as the reference standard. ROC analysis was performed. Optimal sex
      specific CT measurement thresholds were identified that ensured specificity of
      90% or greater and maximized sensitivity. RESULTS: The prevalence of chamber
      enlargement in men was 26% for RAE, 11% for RVE, 40% for LAE, and 24% for LVE. In
      women the prevalence was 16% for RAE, 15% for RVE, 27% for LAE, and 12% for LVE.
      The following CT measurement thresholds were optimal: for RAE, RA transverse
      diameter >= 67 mm for men (AUC, 0.825) and >= 64 mm for women (AUC, 0.926); for
      RVE, RV transverse diameter >= 60 mm for men (AUC, 0.846) and >= 57 mm for women
      (AUC, 0.858); for LAE, LA anteroposterior diameter >= 50 mm for men (AUC, 0.795)
      and >= 45 mm for women (AUC, 0.841); for LVE, LV transverse diameter >= 58 mm for
      men (AUC, 0.917) and >= 53 mm for women (AUC, 0.840). CONCLUSION: Cardiac chamber
      enlargement can be identified with high specificity and reasonable sensitivity on
      axial chest CT images by use of sex-specific measurement thresholds.

PMID- 30240289
TI  - Contrast-Enhanced 3-T Perfusion MRI With Quantitative Analysis for the
      Characterization of Musculoskeletal Tumors: Is It Worth the Trouble?
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance
      of quantitative perfusion parameters in 3-T MRI for benign-malignant
      differentiation in musculoskeletal tumors. SUBJECTS AND METHODS: Ninety-five
      patients with histologically proven musculoskeletal tumors were prospectively
      included in this study. All patients underwent 3-T contrast-enhanced perfusion
      MRI with T1 mapping. The extended Tofts pharmacokinetic model was used to obtain
      four semiquantitative and four quantitative perfusion parameters for each tumor.
      Two radiologists evaluated all images and manually placed the ROIs in consensus.
      RESULTS: The 95 patients had 57 (59%) benign and 38 (41%) malignant tumors.
      Thirty-seven (39%) were bone and 58 (61%) were soft-tissue tumors. No significant
      differences were found in the perfusion parameters of benign and malignant tumors
      (p = 0.105-0.609). The best performance for benign-malignant differentiation was
      found for fractional volume of the extravascular extracellular space, which
      yielded 79% and 38% sensitivity and specificity. When soft-tissue tumors were
      considered, the transfer constant from plasma to the extravascular extracellular
      space exhibited a significant difference (p = 0.028) and had 79% and 27%
      sensitivity and specificity. CONCLUSION: Quantitative perfusion MRI had fair
      sensitivity and poor specificity for benign-malignant differentiation, which was
      similar to that obtained with semiquantitative parameters.

PMID- 30240290
TI  - Not One of the Usual Suspects: MRI Features of Insertional Lateral Cord Plantar
      Fasciopathy.
AB  - OBJECTIVE: The purpose of this article is to report MRI findings of insertional
      lateral cord plantar fasciopathy and review the presenting symptoms of the
      condition and suspected diagnoses. CONCLUSION: Lateral cord plantar fasciopathy
      presents with pain and swelling at the lateral midfoot, which are typically
      clinically suspected to be caused by fifth metatarsal (MT) base stress fracture
      of peroneal tendon abnormalities. The MRI findings are identical to those seen in
      association with the more commonly occurring central cord plantar fasciopathy,
      which has a calcaneal origin, but the findings affect the insertion of the
      lateral cord onto the plantar lateral base of the fifth MT.

PMID- 30240291
TI  - MRI-Based Apparent Diffusion Coefficient for Predicting Pathologic Response of
      Rectal Cancer After Neoadjuvant Therapy: Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: The purpose of this study was to assess the use of apparent diffusion
      coefficient (ADC) during DWI for predicting complete pathologic response of
      rectal cancer after neoadjuvant therapy. MATERIALS AND METHODS: A systematic
      review of available literature was conducted to retrieve studies focused on the
      identification of complete pathologic response of locally advanced rectal cancer
      after neoadjuvant chemoradiation, through the assessment of ADC evaluated before,
      after, or both before and after treatment, as well as in terms of the difference
      between pretreatment and posttreatment ADC. Pooled mean pretreatment ADC,
      posttreatment ADC, and Delta-ADC (calculated as posttreatment ADC minus
      pretreatment ADC divided by pretreatment ADC and multiplied by 100) in complete
      responders versus incomplete responders were calculated. For each parameter, we
      also pooled sensitivity and specificity and calculated the area under the summary
      ROC curve. RESULTS: We found 10 prospective and eight retrospective studies.
      Overall, pathologic complete response was observed in 22.2% of patients. Pooled
      mean pretreatment ADC in complete responders was 0.84 * 10-3 mm2/s versus 0.89 *
      10-3 mm2/s in incomplete responders (p = 0.33). Posttreatment ADC values were
      1.51 * 10-3 mm2/s and 1.29 * 10-3 mm2/s, in complete and incomplete responders,
      respectively (p = 0.00001). The Delta-ADC percentages were also significantly
      higher in complete responders than in incomplete responders (59.7% vs 29.7%,
      respectively, p = 0.016). Pooled sensitivity, specificity, and AUC were 0.743,
      0.755, and 0.841 for pretreatment ADC; 0.800, 0.737, and 0.782 for posttreatment
      ADC; and 0.832, 0.806, and 0.895 for Delta-ADC. CONCLUSION: Use of ADC during DWI
      is a promising technique for assessment of results of neoadjuvant treatment of
      rectal cancer.

PMID- 30240292
TI  - Contrast-Enhanced Spectral Mammography in Women With Intermediate Breast Cancer
      Risk and Dense Breasts.
AB  - OBJECTIVE: The purpose of this study was to compare the diagnostic performance of
      contrast-enhanced spectral mammography (CESM) and ultrasound with that of
      standard digital mammography for breast cancer screening of women at intermediate
      risk who have dense breasts. MATERIALS AND METHODS: In a retrospective cohort of
      611 consecutively registered women who underwent screening CESM from 2012 to
      2017, BI-RADS scores of the screening modalities were compared with actual
      disease status, assessed by histopathologic analysis or imaging follow-up.
      Sensitivity, specificity, and positive and negative predictive values were
      calculated. RESULTS: Among the 611 women included, 48.3% (295/611) had family or
      personal history of breast cancer, the BI-RADS breast density score was C or D in
      93.1% (569/611). The mean follow-up period was 20 months. Mammography depicted 11
      of 21 malignancies, sensitivity of 52.4%, specificity of 90.5% (534/590),
      positive predictive value of 16.4% (11/67), and negative predictive value of
      98.2% (534/544). CESM depicted 19 of 21 malignancies, sensitivity of 90.5%,
      specificity of 76.1% (449/590), positive predictive value of 11.9% (19/160), and
      negative predictive value of 99.6% (449/451). Differences in sensitivity (p =
      0.008) and specificity (p < 0.001) were statistically significant. Adjunct
      ultrasound revealed 73 additional suspicious findings; all were false-positive.
      In 39 women MRI was needed to assess screening abnormalities; two MRI-guided
      biopsies were performed and yielded one cancer. The incremental cancer detection
      rate of CESM was 13.1/1000 women (95% CI, 6.1-20.1). Of eight cancers seen only
      with CESM, seven were invasive (mean size, 9 mm; two of four cancers lymph-node
      positive). CONCLUSION: CESM was significantly more sensitive than standard
      digital mammography for detecting breast cancer in this screening population. No
      added benefit was found in the performance of ultrasound as an adjunct to CESM
      screens with negative results. CESM may be a valuable supplemental screening
      modality for women at intermediate risk who have dense breasts.

PMID- 30240293
TI  - Readability of Online Information Related to Pediatric Radiation Safety From
      Societal Websites.
AB  - OBJECTIVE: The Internet has become a major readily available source of health
      care education. Pediatric radiation safety is a complex topic with evolving
      safety guidelines. The purpose of this study is to assess the readability of
      publically available online information pertaining to pediatric radiation safety
      available on the websites of radiologic and pediatric societies. MATERIALS AND
      METHODS: Online information related to pediatric radiation safety that is
      available on the Society for Pediatric Radiology website and the websites
      RadiologyInfo (sponsored by the Radiological Society of North America and the
      American College of Radiology) and HealthyChildren.org (sponsored by the American
      Academy of Pediatrics) was evaluated for readability. Each article was assessed
      using six readability tests, which use either a grade level or a numeric scale to
      categorize readability. ANOVA was used to compare readability levels and
      intraclass correlation coefficients for analytic reliability. RESULTS: A total of
      54 articles were included in the analysis. Three of the articles were written
      below the eighth-grade reading level. The mean readability ranged from grades
      12.1 to 14.8 among the five different grade level-based readability scales used.
      The mean readability determined using the numeric scale was 37.3 (which
      identified readability as difficult), with 91% of articles categorized as very
      difficult, difficult, or fairly difficult and with no article categorized as easy
      or very easy. No difference in readability was found among the different web
      sources (p = 0.46-0.85). CONCLUSION: Overall, the readability of information
      pertaining to pediatric radiation safety that is available on radiology and
      pediatric medical society websites is at a level that is too difficult for the
      average adult.

PMID- 30240294
TI  - Differentiation of Papillary Renal Cell Carcinoma Subtypes on MRI: Qualitative
      and Texture Analysis.
AB  - OBJECTIVE: The objective of this study was to determine whether quantitative
      texture analysis of MR images would improve the ability to distinguish papillary
      renal cell carcinoma (RCC) subtypes, compared with analysis of qualitative MRI
      features alone. MATERIALS AND METHODS: A total of 47 pathologically proven
      papillary RCC tumors were retrospectively evaluated, with 31 (66%) classified as
      type 1 tumors and 16 (34%) classified as type 2 tumors. MR images were reviewed
      by two readers to determine tumor size, signal intensity, heterogeneity,
      enhancement pattern, margins, perilesional stranding, vein thrombosis, and
      metastasis. Quantitative texture analysis of gray-scale images was performed. A
      logistic regression was derived from qualitative and quantitative features. Model
      performance was compared with and without texture features. RESULTS: The
      significant qualitative MR features noted were necrosis, enhancement appearance,
      perilesional stranding, and metastasis. A multivariable model based on
      qualitative features did not identify any factor as an independent predictor of a
      type 2 tumor. The logistic regression model for predicting papillary RCCs on the
      basis of qualitative and quantitative analysis identified probability of the 2D
      volumetric interpolated breath-hold examination (VIBE) sequence (AUC value, 0.87;
      95% CI, 0.77-0.98) as an independent predictor of a type 2 tumor. No difference
      in the model AUC value was noted when texture features were included in the
      analysis; however, the model had increased sensitivity and an improved predictive
      value without loss of specificity. CONCLUSION: The addition of texture analysis
      to analysis of conventional qualitative MRI features increased the probability of
      predicting a type 2 papillary RCC tumor, which may be clinically important.

PMID- 30240295
TI  - Diagnostic Performance of Adaptive 4D Volume Perfusion CT for Detecting
      Metastatic Cervical Lymph Nodes in Head and Neck Squamous Cell Carcinoma.
AB  - OBJECTIVE: The purpose of this study was to investigate the diagnostic
      performance of adaptive 4D volume perfusion CT covering the entire neck for
      detecting metastatic nodes in patients with head and neck squamous cell
      carcinoma. SUBJECTS AND METHODS: Thirty patients with histologically confirmed
      disease were enrolled. The relation between perfusion parameters and nodal size
      was analyzed, and perfusion parameters were compared between metastatic and
      benign nodes. The diagnostic capability for detecting metastatic nodes was
      evaluated. RESULTS: Significant inverse correlations with nodal size were found
      for blood flow (r = -0.40, p = 0.002), blood volume (r = -0.32, p = 0.02), and
      permeability surface product (r = -0.27, p = 0.04) of the metastatic nodes. All
      three parameters had significantly higher values in association with nodal
      maximum diameter < 10 mm compared with diameter >= 10 mm (blood flow, p = 0.004;
      blood volume, p = 0.01; permeability surface product, p = 0.02). Among the nodes
      with maximum diameter < 10 mm, blood flow of the metastatic nodes was
      significantly higher than that of the benign nodes (p = 0.02), whereas among the
      nodes >= 10 mm in diameter, the mean transit time of the metastatic nodes was
      significantly lower than that of the benign nodes (p = 0.04). In multivariate
      analysis, blood flow in nodes with maximum diameter < 10 mm had a significant
      association with the detection of metastatic nodes. The sensitivity and
      specificity of blood flow for differentiating metastatic from benign nodes were
      73.3% and 70.8%. CONCLUSION: Findings from 4D volume perfusion CT covering the
      entire neck may be informative for characterization of cervical nodes. It is
      worthwhile to include the examination in nodal staging of head and neck squamous
      cell carcinoma.

PMID- 30240297
TI  - Comparison of MRI and PET as Potential Surrogate Endpoints for Treatment Response
      After Stereotactic Radiosurgery in Patients With Brain Metastasis.
AB  - OBJECTIVE: The purpose of this study is to compare the diagnostic performance of
      MRI and PET for differentiating tumor recurrence from radiation necrosis in
      patients with brain metastasis treated with stereotactic radiosurgery. MATERIALS
      AND METHODS: The Ovid-Medline and Embase databases were searched up to November
      11, 2017, to find relevant studies. Pooled sensitivity and specificity from
      entire included studies were obtained using hierarchic logistic regression
      modeling. Metaregression was performed. RESULTS: Twenty studies including 728
      patients with 872 brain metastases were selected. MRI showed a pooled sensitivity
      of 84% (95% CI, 72-91%) and specificity of 88% (95% CI, 71-96%). PET showed a
      pooled sensitivity of 84% (95% CI, 78-88%) and specificity of 86% (95% CI, 81
      90%). There were no statistically significant differences in the diagnostic
      performance of MRI and PET using indirect (p = 0.80) or direct (p = 0.48)
      comparisons. The diagnostic performance of advanced MRI was significantly higher
      than that of conventional MRI (p = 0.01). Advanced MRI (sensitivity, 86% [95% CI,
      74-93%]; specificity, 95% [95% CI, 82-98%]) showed a significantly higher
      diagnostic performance than did PET (p < 0.01). All the included studies used
      perfusion MRI as an advanced MRI technique. CONCLUSION: MRI and PET showed high
      diagnostic performance for the detection of tumor recurrence after stereotactic
      radiosurgery in patients with brain metastasis. There was no significant
      difference in the diagnostic performance between MRI and PET. Because of
      heterogeneity and paucity in studies, caution may be needed in applying the
      results.

PMID- 30240296
TI  - Head-to-Head Comparison Between Biparametric and Multiparametric MRI for the
      Diagnosis of Prostate Cancer: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: The purpose of this study was to perform a systematic review and meta
      analysis of a head-to-head comparison between the performance of biparametric MRI
      (bpMRI; only T2-weighted imaging and DWI) and that of multiparametric MRI (mpMRI;
      T2-weighted imaging, DWI, dynamic contrast-enhanced MRI) for the diagnosis of
      prostate cancer. MATERIALS AND METHODS: The PubMed and Embase databases were
      searched up to November 11, 2017. The search included diagnostic test accuracy
      studies that compared bpMRI and mpMRI for prostate cancer diagnosis with
      histopathologic findings from biopsy or radical prostatectomy as the reference
      standard. Methodologic quality was evaluated with the revised Quality Assessment
      of Diagnostic Accuracy Studies tool. Sensitivity and specificity were pooled by
      means of bivariate and hierarchic summary ROC (HSROC) modeling and graphically
      presented with HSROC plots. Meta-regression analysis and multiple subgroup
      analyses were used to compare the diagnostic performances of bpMRI and mpMRI.
      RESULTS: Twenty studies (2142 patients) were included. Pooled sensitivity and
      specificity were 0.74 (95% CI, 0.66-0.81) and 0.90 (95% CI, 0.86-0.93) for bpMRI
      and 0.76 (95% CI, 0.69-0.82) and 0.89 (95% CI, 0.85-0.93) for mpMRI. MRI protocol
      (bpMRI vs mpMRI) was not a significant factor in heterogeneity (p = 0.83). In 26
      subgroups evaluated on the basis of stratification to clinicopathologic, study,
      and MRI characteristics, MRI protocol (bpMRI vs mpMRI) was not a significant
      factor in heterogeneity in any subgroup (p = 0.25-0.97). CONCLUSION: A head-to
      head comparison showed that the performance of bpMRI was similar to that of mpMRI
      in the diagnosis of prostate cancer. Consistent results were found in multiple
      subgroup analyses.

PMID- 30240298
TI  - Routine MRI With DWI Sequences to Detect Liver Metastases in Patients With
      Potentially Resectable Pancreatic Ductal Carcinoma and Normal Liver CT: A
      Prospective Multicenter Study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the performance of
      systematic MRI with DWI for the detection of liver metastases (LM) in patients
      with potentially resectable pancreatic ductal carcinoma and normal liver findings
      at CT. SUBJECTS AND METHODS: Patients with potentially resectable pancreatic
      ductal carcinoma and a normal liver at CT were enrolled in a prospective
      multicenter study between March 2011 and July 2013 and underwent preoperative
      MRI. The reference standard was pathologic analysis of detected hepatic lesions.
      RESULTS: A total of 118 patients were enrolled. MRI depicted liver lesions that
      were not visible at CT in 16 patients. All lesions were visualized both with and
      without DWI. Lesions were LM in 12 (10.2%) patients and were confirmed in seven
      patients by preoperative biopsy, four by intraoperative frozen section, and one
      at 6-month follow-up evaluation after pancreatic resection. All but one liver
      metastatic lesion diagnosed with MRI were smaller than 10 mm. Four of 118 (3.4%)
      patients had a false-positive diagnosis of LM at MRI and remained LM free after a
      follow-up period of 24 months or longer. Three of 102 (2.9%) patients with normal
      MRI findings had subcapsular LM that were diagnosed intraoperatively. At follow
      up, 99 of 118 (83.9%) patients were LM free after a mean of 24 months. The
      patient-based sensitivity of MRI for the detection of LM was 80.0% (95% CI, 51.9
      95.7%); specificity, 96.1% (95% CI, 90.4-98.9%); positive predictive value, 75.0%
      (95% CI, 47.6-92.7%); and negative predictive value, 97.1% (95% CI, 91.6-99.4%).
      CONCLUSION: Compared with CT, preoperative MRI improves the detection of LM in
      patients with potentially resectable pancreatic ductal carcinoma and may change
      management and the rate of unnecessary laparotomy and pancreatectomy for 10% of
      patients.

PMID- 30240299
TI  - Differentiation of Predominantly Solid Enhancing Lipid-Poor Renal Cell Masses by
      Use of Contrast-Enhanced CT: Evaluating the Role of Texture in Tumor Subtyping.
AB  - OBJECTIVE: The purpose of this study was to assess the accuracy of a panel of
      texture features extracted from clinical CT in differentiating benign from
      malignant solid enhancing lipid-poor renal masses. MATERIALS AND METHODS: In a
      retrospective case-control study of 174 patients with predominantly solid
      nonmacroscopic fat-containing enhancing renal masses, 129 cases of malignant
      renal cell carcinoma were found, including clear cell, papillary, and chromophobe
      subtypes. Benign renal masses-oncocytoma and lipid-poor angiomyolipoma-were found
      in 45 patients. Whole-lesion ROIs were manually segmented and coregistered from
      the standard-of-care multiphase contrast-enhanced CT (CECT) scans of these
      patients. Pathologic diagnosis of all tumors was obtained after surgical
      resection. CECT images of the renal masses were used as inputs to a CECT texture
      analysis panel comprising 31 texture metrics derived with six texture methods.
      Stepwise logistic regression analysis was used to select the best predictor among
      all candidate predictors from each of the texture methods, and their performance
      was quantified by AUC. RESULTS: Among the texture predictors aiding renal mass
      subtyping were entropy, entropy of fast-Fourier transform magnitude, mean,
      uniformity, information measure of correlation 2, and sum of averages. These
      metrics had AUC values ranging from good (0.80) to excellent (0.98) across the
      various subtype comparisons. The overall CECT-based tumor texture model had an
      AUC of 0.87 (p < 0.05) for differentiating benign from malignant renal masses.
      CONCLUSION: The CT texture statistical model studied was accurate for
      differentiating benign from malignant solid enhancing lipid-poor renal masses.

PMID- 30240300
TI  - Metal Artifact Reduction in Virtual Monoenergetic Spectral Dual-Energy CT of
      Patients With Metallic Orthopedic Implants in the Distal Radius.
AB  - OBJECTIVE: The purpose of this study was to evaluate the image quality of virtual
      monoenergetic images obtained from dual-layer-detector spectral CT of patients
      with metallic orthopedic implants of the distal radius. MATERIALS AND METHODS: A
      retrospective analysis was performed between April 2016 and January 2017. Forty
      three consecutively registered patients (33 women, 10 men; mean age, 50.7 +/-
      15.4 years) with metallic implants for distal radius fractures underwent dual
      layer-detector spectral CT. Sixteen virtual monoenergetic image sets ranging from
      50 to 200 keV were generated from the single slice with the most pronounced low
      attenuation artifact from implants. Image quality was quantitatively assessed on
      the basis of the attenuation of the artifacts and reference tissue, background
      image noise, and artifact index. Qualitative assessment included degree of
      artifact, diagnostic image quality of the periimplant bones, and delineation of
      fracture lines. The Friedman rank sum test and kappa analysis were used for
      statistical analysis. RESULTS: There were statistically significant differences
      in quantitative and qualitative parameters at different monoenergy levels (all p
      < 0.001). Artifact index was the lowest at 120 keV. Low-attenuation artifacts in
      the periimplant regions were least pronounced at 110 keV, and the diagnostic
      image quality of periimplant bone was best at 130 keV. Fracture lines were well
      delineated in all cases at 80-110 keV (p < 0.001). CONCLUSION: The optimal energy
      setting for incurring the fewest metallic artifacts and obtaining the best
      diagnostic image quality from distal radius implants during dual-layer-detector
      spectral CT is the range of 110-130 keV.

PMID- 30240301
TI  - Prevalence of Low-Attenuation Homogeneous Papillary Renal Cell Carcinoma
      Mimicking Renal Cysts on CT.
AB  - OBJECTIVE: The objective of our study was to determine the attenuation range of
      homogeneous papillary renal cell carcinomas (RCCs) on contrast-enhanced CT.
      MATERIALS AND METHODS: This retrospective study was performed at two institutions
      from January 1, 2007, to January 1, 2017. Multiphasic CT studies with and without
      IV contrast material of 114 patients with pathologically proven papillary RCCs
      were independently reviewed by two sets of two abdominal radiologists. Seventy
      two cases were excluded because of subjective lesion heterogeneity, leaving 42
      homogeneous RCCs. Three ROIs were placed on all lesions for all CT phases, and
      the mean attenuations were calculated. RESULTS: Mean lesion size was 2.8 cm
      (range, 1.2-11.0 cm). The attenuation range for each CT phase was as follows:
      unenhanced, 14.7-50.7 HU; corticomedullary, 32.2-99.5 HU; portal venous, 40.8
      95.1 HU; nephrographic, 17.9-90.8 HU; and excretory, 18.0-73.0 HU. Two of 114
      (1.8%; 95% CI, 0.2-6.5%) RCCs were homogeneous and less than 30 HU on the portal
      venous or nephrographic phase. One of these RCCs was a solid hypoenhancing mass,
      and the other was a homogeneous cystic RCC. Of the cases with an unenhanced
      phase, three of 107 (2.8%; 95% CI, 0.6-8.8%) were both homogeneous and were less
      than 20 HU in attenuation. CONCLUSION: Papillary RCCs are rarely both
      subjectively homogeneous and less than 20 HU at unenhanced CT and less than 30 HU
      at portal venous or nephrographic phase CT.

PMID- 30240302
TI  - Uncovered Medial Meniscus Sign on Knee MRI: Evidence of Lost Brake Stop Mechanism
      of the Posterior Horn Medial Meniscus.
AB  - OBJECTIVE: The objective of our study was to evaluate the association between
      anterior tibial translation and injuries on the posterior horn medial meniscus
      (PHMM) and the integrity of the brake stop mechanism of the PHMM in the anterior
      cruciate ligament (ACL)-deficient knee. MATERIALS AND METHODS: This retrospective
      study included 85 consecutive patients with an arthroscopically confirmed
      complete ACL tear. Anterior tibial translation was quantitatively measured using
      sagittal MRI at the midpoint of the lateral femoral condyle. The "uncovered
      medial meniscus" sign was considered positive if a vertical line tangent to the
      posteriormost margin of the medial tibial plateau intersected the PHMM at the
      midpoint of the medial femoral condyle on sagittal MRI. Concomitant injuries on
      the structures of the posteromedial and posterolateral corners of the knee,
      including PHMM tear and meniscal ramp lesion, were recorded. Stratified subgroup
      analysis and multivariable regression analysis were performed to identify factors
      associated with anterior tibial translation. RESULTS: The uncovered medial
      meniscus sign was positive in 21.2% (18/85) of patients and was significantly
      associated with anterior tibial translation. In the stratified subgroup analysis
      and multivariable regression analysis, positive uncovered medial meniscus sign
      consistently showed a significant association with anterior tibial translation
      and generated an additional 2.8 mm of anterior tibial translation. Other
      injuries, including PHMM tear and meniscal ramp lesion, were not associated with
      anterior tibial translation. CONCLUSION: The uncovered medial meniscus sign
      showed a statistically significant correlation with anterior tibial translation
      and could be a useful marker for the lost brake stop mechanism of PHMM in the ACL
      deficient knee.

PMID- 30240303
TI  - Optimal Timing of the First Barium Swallow Examination for Diagnosis of Pyriform
      Sinus Fistula.
AB  - OBJECTIVE: Observation of a sinus tract during a barium swallow examination is
      important for the diagnosis of pyriform sinus fistula; however, to our knowledge,
      no reports have existed regarding the optimal timing of the examination in
      relation to the onset of symptoms. The purpose of this study was to compare the
      timing of the examination, patient age, the number of inflammatory episodes that
      occurred before the examination, and the barium concentration used for
      examinations with true-positive results versus those with false-negative results
      for the diagnosis of pyriform sinus fistula. MATERIALS AND METHODS: Twenty-three
      children with pyriform sinus fistula were included. The timing of the
      examination, patient age, the number of the inflammatory episodes that occurred
      before examination, and the barium concentration used were compared between
      examinations with true-positive results and examinations with false-negative
      results, by use of the Mann-Whitney U test. RESULTS: The examination had true
      positive results for 60.9% (14/23) of patients and false-negative results for
      39.1% (9/23) of patients. The mean (+/- SD) interval since the onset of symptoms
      was significantly shorter for patients with false-negative examination results
      than for those with true-positive examination results (26.33 +/- 21.17 days vs
      48.57 +/- 17.67 days; p = 0.020). By 6 weeks after the onset of symptoms, more
      than half of the examinations had false-negative results. No significant
      difference in patient age (p = 0.238) or number of previous inflammatory episodes
      (p = 0.431) existed between examinations with true-positive and false-negative
      results; however, a significant difference was noted in the mean barium
      concentration used (88.57% +/- 31.53% vs 52.86% +/- 18.68% weight/volume,
      respectively; p = 0.014). CONCLUSION: Barium swallow examinations with false
      negative results were significantly more likely when the examination was
      performed soon after the onset of symptoms. Therefore, early first examinations
      would not be recommended for the diagnosis of pyriform sinus fistula, especially
      in terms of radiation exposure. A higher barium concentration may be useful.

PMID- 30240304
TI  - Predicting Survival Using Pretreatment CT for Patients With Hepatocellular
      Carcinoma Treated With Transarterial Chemoembolization: Comparison of Models
      Using Radiomics.
AB  - OBJECTIVE: The purpose of this study was to investigate the use of radiomics
      features as prognostic biomarkers for predicting the survival of patients treated
      with transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: We retrospectively analyzed 88 patients with HCC treated
      with TACE. High-dimensional quantitative feature analysis was applied to extract
      116 radiomics features of pretreatment CT. A radiomics score model was
      constructed from these features with the use of least absolute shrinkage and
      selection operator Cox regression. A clinical score model was constructed from
      clinical variables with the use of multivariate Cox regression. A combined score
      model was constructed using the radiomics and clinical models. We compared the
      three models (the radiomics score, clinical score, and combined score models) for
      predicting overall survival, using Kaplan-Meier analysis and the log-rank test.
      RESULTS: The following radiomics features were selected for the radiomics score
      model: histogram-based features (median, kurtosis, and energy), shape-based
      features (spherical disproportion and surface-to-volume ratio), gray-level co
      occurrence matrix (GLCM)-based features (energy, informational measure of
      correlation, maximum probability, contrast, and sum average), and intensity size
      zone matrix-based features (size zone variability). For the clinical score model,
      the Child-Pugh score, alpha-fetoprotein level, and HCC size were included. The
      combined score model included five radiomics features (surface area-to-volume
      ratio, kurtosis, median, gray-level co-occurrence matrix contrast, and size zone
      variability) and three clinical factors (Child-Pugh score, alpha-fetoprotein
      level, and HCC size). The combined model was a better predictor of survival
      (hazard ratio, 19.88; p < 0.0001) than the clinical score model or the radiomics
      score model. CONCLUSION: A radiomics approach combined with conventional clinical
      variables could be effective in predicting the survival of patients with HCC
      treated with TACE.

PMID- 30240305
TI  - JOURNAL CLUB: Structured Reporting: The Voice of the Customer in an Ongoing
      Debate About the Future of Radiology Reporting.
AB  - OBJECTIVE: The purpose of this survey was to assess the perception, preferences,
      and expectations of recipients of radiology reports in terms of style and
      content. MATERIALS AND METHODS: In 2016, 3610 general practitioners and hospital
      based physicians in northwestern Switzerland were invited to participate in a
      survey. The questionnaire consisted of a demographics section, a current
      satisfaction section, and a section addressing expectations and preferences
      concerning content and structure. The participants were asked to rate (range of
      scores, 1-10) four different layouts of radiology reports (text, structured text,
      tables, images) in terms of comprehensibility and efficiency. RESULTS: A total of
      570 participants (132 general practitioners, 438 hospital physicians at five
      hospitals) completed the survey. Regarding layout preferences, structured text
      (median, 8) and images (median, 7) rated highest in terms of readability, time
      saving, and helpfulness in communication with patients compared with tables
      (median, 5) and unstructured text (median, 4). The participants responded that
      reports should give normal values as references (60% [344/570] positive), mention
      normal structures (50% [286/570] positive), and list additional findings in the
      summary (89% [507/570] positive). Positive ratings for a confidence statement
      (54% [308/570]), a list of differential diagnoses (89% [507/570]), and a
      recommendation (66% [377/570]) indicated an active radiologist's role is
      appreciated. Eighty percent (459/570) of respondents stated a report should allow
      fast and efficient reading. CONCLUSION: The voice of the customer approach shows
      referring physicians have distinct expectations and specific but predominantly
      coherent preferences with regard to radiology reporting. The survey results offer
      valuable specific feedback and a strong argument in favor of structured
      reporting.

PMID- 30240306
TI  - Imaging Features of Nonmalignant and Malignant Architectural Distortion Detected
      by Tomosynthesis.
AB  - OBJECTIVE: The objective of our study was to determine the ability of
      tomosynthesis (3D) to detect nonmalignant and malignant architectural distortion
      (AD) on 3D screening mammograms compared with digital mammography (2D) only and
      to correlate the 3D imaging features of nonmalignant and malignant AD with
      pathology findings. MATERIALS AND METHODS: For this single-institution
      retrospective study, screening mammography reports from October 1, 2012, to
      December 1, 2016, that included AD as a finding were reviewed. Associated
      additional imaging studies and pathology results were also reviewed. RESULTS:
      Three-dimensional mammography showed statistically significant increased
      detection of both nonmalignant and malignant AD compared with 2D only (0.10%
      [24/24,902 examinations] vs 0.01% [1/9470 examinations], p < 0.05; and 0.21%
      [52/24,902 examinations] vs 0.07% [7/9470 examinations], p < 0.05, respectively).
      Higher percentages of nonmalignant AD (16%) were occult on ultrasound compared
      with malignant AD (3%). The pathologic diagnoses of nonmalignant AD included
      radial scar (42%), sclerosing adenosis (16%), stromal or dense fibrosis (16%),
      and other miscellaneous benign causes (25%). Morphologically, nonmalignant AD was
      more likely to show symmetric or spoke-wheel spiculation appearance (58% vs 2%, p
      < 0.05) and central lucency (25% vs 0%, p < 0.05) than malignant AD, whereas
      malignant AD was more likely to show asymmetric spiculation (98% vs 42%, p <
      0.05) and central mass 60% vs 0%, p < 0.05) than nonmalignant AD. CONCLUSION:
      Malignant AD and nonmalignant AD are more readily detected by 3D mammography than
      2D mammography. Three-dimensional imaging features of AD can help to distinguish
      nonmalignant types in which symmetric or spoke-wheel spiculation with central
      lucency are more often seen and are more often occult on ultrasound.

PMID- 30240307
TI  - An Analysis of the Brain Systems Involved with Producing Letters by Hand.
AB  - Complex visual-motor behaviors dominate human-environment interactions. Letter
      production, writing individual letters by hand, is an example of a complex visual
      motor behavior composed of numerous behavioral components, including the required
      motor movements and the percepts that those motor movements create. By
      manipulating and isolating components of letter production, we provide
      experimental evidence that this complex visual-motor behavior is supported by a
      widespread neural system that is composed of smaller subsystems related to
      different sensorimotor components. Adult participants hand-printed letters with,
      and without, "ink" on an MR-safe digital writing tablet, perceived static and
      dynamic representations of their own handwritten letters, and perceived typeface
      letters during fMRI scanning. Our results can be summarized by three main
      findings: (1) Frontoparietal systems were associated with the motor component of
      letter production, whereas temporo-parietal systems were more associated with the
      visual component. (2) The more anterior regions of the left intraparietal sulcus
      were more associated with the motor component, whereas the more posterior regions
      were more associated with the visual component, with an area of visual-motor
      overlap in the posterior intraparietal sulcus. (3) The left posterior
      intraparietal sulcus and right fusiform gyrus responded similarly to both visual
      and motor components, and both regions also responded more during the perception
      of one's own handwritten letters compared with perceiving typed letters. These
      findings suggest that the neural systems recruited during complex visual-motor
      behaviors are composed of a set of interrelated sensorimotor subsystems that
      support the full behavior in different ways and, furthermore, that some of these
      subsystems can be rerecruited during passive perception in the absence of the
      full visual-motor behavior.

PMID- 30240308
TI  - Subgoal- and Goal-related Reward Prediction Errors in Medial Prefrontal Cortex.
AB  - A longstanding view of the organization of human and animal behavior holds that
      behavior is hierarchically organized, in other words, directed toward achieving
      superordinate goals through the achievement of subordinate goals or subgoals.
      However, most research in neuroscience has focused on tasks without hierarchical
      structure. In past work, we have shown that negative reward prediction error
      (RPE) signals in medial prefrontal cortex (mPFC) can be linked not only to
      superordinate goals but also to subgoals. This suggests that mPFC tracks
      impediments in the progression toward subgoals. Using fMRI of human participants
      engaged in a hierarchical navigation task, here we found that mPFC also processes
      positive prediction errors at the level of subgoals, indicating that this brain
      region is sensitive to advances in subgoal completion. However, when subgoal RPEs
      were elicited alongside with goal-related RPEs, mPFC responses reflected only the
      goal-related RPEs. These findings suggest that information from different levels
      of hierarchy is processed selectively, depending on the task context.

PMID- 30240309
TI  - Prefrontal and Hippocampal Structure Predict Statistical Learning Ability in
      Early Childhood.
AB  - Statistical learning can be used to gain sensitivity to many important
      regularities in our environment, including structure that is foundational to
      language and visual perception. As yet, little is known about how statistical
      learning takes place in the human brain, especially in children's developing
      brains and with regard to the broader neurobiology of learning and memory. We
      therefore explored the relationship between statistical learning and the
      thickness and volume of structures that are traditionally implicated in
      declarative and procedural memory, focusing specifically on the left inferior
      pFC, the hippocampus, and the caudate during early childhood (5-8.5 years). We
      found that the thickness of the left inferior frontal cortex and volume of the
      right hippocampus predicted statistical learning ability in young children.
      Importantly, these regions did not change in thickness or volume with age, but
      the relationship between learning and the right hippocampus interacted with age
      such that older children's hippocampal structure more strongly predicted
      performance. Overall, the data show that children's statistical learning is
      supported by multiple neural structures that are more broadly implicated in
      learning and memory, especially declarative memory (hippocampus) and
      attention/top-down control (the pFC).

PMID- 30240310
TI  - Individual Differences in Resting-state Brain Rhythms Uniquely Predict Second
      Language Learning Rate and Willingness to Communicate in Adults.
AB  - The current study used quantitative electroencephalography (qEEG) to characterize
      individual differences in neural rhythms at rest and to relate them to fluid
      reasoning ability, to first language proficiency, and to subsequent second
      language (L2) learning ability, with the goal of obtaining a better understanding
      of the neurocognitive bases of L2 aptitude. Mean spectral power, laterality, and
      coherence metrics were extracted across theta, alpha, beta, and gamma frequency
      bands obtained from eyes-closed resting-state qEEG data from 41 adults aged 18-34
      years. Participants then completed 8 weeks of French training using a virtual
      language and cultural immersion software. Results replicate and extend previous
      studies showing that faster learners have higher beta power recorded over right
      hemisphere (RH) electrode sites, greater laterality (RH - LH/RH + LH) of alpha
      and beta bands, and greater coherence between RH frontotemporal sites across all
      frequencies, although only coherence measures survived multiple comparisons.
      Increased coherence within and between RH networks was also associated with
      greater posttest declarative memory scores and with more accurate speech during
      learning. Total speech attempts, in contrast, correlated with bilaterally
      distributed small-world network configurations, as indexed by lower power and
      coherence over high-frequency (beta and gamma) bands recorded over frontotemporal
      networks in both hemispheres. Results from partial correlations and regression
      analyses suggest that the neural predictors of L2 learning rate, posttest
      proficiency, and total speech attempts varied in their degree of overlap with
      qEEG correlates of first language proficiency and fluid reasoning abilities, but
      that neural predictors alone explained 26-60% of the variance in L2 outcomes.

PMID- 30240311
TI  - Hemifield-specific Correlations between Cue-related Blood Oxygen Level Dependent
      Activity in Bilateral Nodes of the Dorsal Attention Network and Attentional
      Benefits in a Spatial Orienting Paradigm.
AB  - The dorsal attention network (DAN) is known to be involved in shifts of spatial
      attention or orienting. However, the involvement of each hemisphere in shifts to
      either hemifield is still a matter of debate. In this study, interindividual
      hemifield-specific attentional benefits in RTs were correlated with cue-related
      blood oxygen level dependent responses specific to directive cues in the left and
      right frontal and posterior nodes of the DAN, measured in a Spatial Orienting
      Paradigm. The pattern of correlations was analyzed with respect to its fit with
      three existing hypotheses of spatial attention control: the contralateral, right
      dominance, and hybrid hypotheses. Results showed that activation in frontal and
      parietal nodes of the DAN could explain a significant proportion of the
      interindividual variance in attentional benefits. Although we found that benefits
      in the right hemifield correlated with cue-related activity in the left, as well
      as the right, DAN and that the pattern of correlations fits best with the right
      dominance hypothesis, there were no significant correlations between left
      benefits and activation in the right (as well as left) DAN, which precludes the
      conclusion that our data support the right dominance hypothesis and might instead
      point toward a potential qualitative difference between leftward and rightward
      shifts of attention. In conclusion, this study demonstrates that behavioral
      effects of orienting can be linked to activation changes in the DAN, and it
      raises new questions with respect to the involvement of the frontal and parietal
      nodes in each hemisphere in hemifield-specific orienting.

PMID- 30240312
TI  - A Varying Role for Abstraction in Models of Category Learning Constructed from
      Neural Representations in Early Visual Cortex.
AB  - The human capacity for visual categorization is core to how we make sense of the
      visible world. Whereas a substantive body of research in cognitive neuroscience
      has localized this capacity to regions of human visual cortex, relatively few
      studies have investigated the role of abstraction in how representations for
      novel object categories are constructed from the neural representation of
      stimulus dimensions. Using human fMRI coupled with formal modeling of observer
      behavior, we assess a wide range of categorization models that vary in their
      level of abstraction from collections of subprototypes to representations of
      individual exemplars. The category learning tasks range from simple linear and
      unidimensional category rules to complex crisscross rules that require a
      nonlinear combination of multiple dimensions. We show that models based on neural
      responses in primary visual cortex favor a variable, but often limited, extent of
      abstraction in the construction of representations for novel categories, which
      differ in degree across tasks and individuals.

PMID- 30240313
TI  - Conscious Perception: Time for an Update?
AB  - Understanding the neural mechanisms underlying conscious perception has become a
      central endeavor in cognitive neuroscience. In theories of conscious perception,
      a stimulus gaining conscious access is usually considered as a discrete neuronal
      event to be characterized in time or space, sometimes referred to as a conscious
      "episode." Surprisingly, the alternative hypothesis according to which conscious
      perception is a dynamic process has rarely been considered. Here, we discuss this
      hypothesis and its implications. We show how it can reconcile inconsistent
      empirical findings on the timing of the neural correlates of consciousness and
      make testable predictions. According to this hypothesis, a stimulus is
      consciously perceived for as long as it is recoded to fit an ongoing stream
      composed of all other perceived stimuli. We suggest that this "updating" process
      is governed by at least three factors (1) context, (2) stimulus saliency, and (3)
      observers' goals. Finally, this framework forces us to reconsider the typical
      distinction between conscious and unconscious information processing.

PMID- 30240314
TI  - Medial Temporal Lobe Amnesia Is Associated with a Deficit in Recovering Temporal
      Context.
AB  - Medial-temporal lobe (MTL) lesions are associated with severe impairments in
      episodic memory. In the framework of the temporal context model, the hypothesized
      mechanism for episodic memory is the reinstatement of a prior experienced context
      (i.e., "jump back in time"), which relies upon the MTL [Howard, M. W., Fotedar,
      M. S., Datey, A. V., & Hasselmo, M. E. The temporal context model in spatial
      navigation and relational learning: Toward a common explanation of medial
      temporal lobe function across domains. Psychological Review, 112, 75-116, 2005].
      This hypothesis has proven difficult to test in amnesia due to floor-level
      performance by patients in recall tasks. To circumvent this issue, in this study,
      we used a "looped-list" format, in which a set of verbal stimuli was presented
      multiple times in a consistent order. This allowed for comparison of statistical
      properties such as probability of first recall and lag-conditional response
      probability (lag-CRP) between amnesic patients and healthy controls. Results
      revealed that the lag-CRP, but not the probability of first recall, is altered in
      amnesia, suggesting a selective disruption of temporal contiguity. To further
      characterize the results, we fit a scale-invariant version of temporal context
      model [Howard, M. W., Shankar, K. H., Aue, W. R., & Criss, A. H. A distributed
      representation of internal time. Psychological Review, 122, 24-53, 2015] to the
      probability of first recall and lag-CRP curves. The modeling results suggested
      that the deficit in temporal contiguity in amnesia is best described as a failure
      to recover temporal context. These results provide the first direct evidence for
      an impairment in a jump-back-in-time mechanism in patients with MTL amnesia.

PMID- 30240316
TI  - Reply to "Diagnosis of Acute Cholecystitis: Clinical, Radiologic, or Both?"

PMID- 30240315
TI  - The Hippocampus Generalizes across Memories that Share Item and Context
      Information.
AB  - Episodic memory is known to rely on the hippocampus, but how the hippocampus
      organizes different episodes to permit their subsequent retrieval remains
      controversial. One major area of debate hinges on a discrepancy between two
      hypothesized roles of the hippocampus: differentiating between similar events to
      reduce interference and assigning similar representations to events that share
      overlapping items and contextual information. Here, we used multivariate analyses
      of activity patterns measured with fMRI to characterize how the hippocampus
      distinguishes between memories based on similarity at the level of items and/or
      context. Hippocampal activity patterns discriminated between events that shared
      either item or context information but generalized across events that shared
      similar item-context associations. The current findings provide evidence that,
      whereas the hippocampus can reduce mnemonic interference by separating events
      that generalize along a single attribute dimension, overlapping hippocampal codes
      may support memory for events with overlapping item-context relations. This lends
      new insights into the way the hippocampus may balance multiple mnemonic
      operations in adaptively guiding behavior.

PMID- 30240317
TI  - Authorship Revisited: Part 1, Preparation for Submission to AJR.

PMID- 30240318
TI  - Medicolegal-Malpractice and Ethical Issues in RadiologyWill Interpreting
      Radiologic Examinations Too Fast Lead to Being Sued for Malpractice?

PMID- 30240319
TI  - Evaluation of a Nonradioactive Magnetic Marker Wireless Localization Program.

PMID- 30240320
TI  - Use of Unenhanced MR Lymphography to Characterize Idiopathic Chyluria.

PMID- 30240322
TI  - Diagnosis of Acute Cholecystitis: Clinical, Radiologic, or Both?

PMID- 30240321
TI  - Reply to "Use of Unenhanced MR Lymphography to Characterize Idiopathic Chyluria".

PMID- 30240323
TI  - Radiology Resident Supervision.

PMID- 30240324
TI  - MRI-Guided Prostate Interventions.
AB  - OBJECTIVE: The objective of this study is to discuss the use of MRI-guided and
      MRI-directed prostate biopsy techniques, describe how interventional MRI focal
      therapies are used for the treatment of prostate cancer, and predict future
      directions in prostate interventional MRI. The prospect of establishing a center
      for prostate imaging, diagnosis, and treatment is also discussed. CONCLUSION: Low
      or intermediate-risk prostate cancer can be safely treated with MRI-compatible
      devices and techniques such as biopsy, cryoablation, high-intensity focused
      ultrasound, or focal laser ablation performed from a transrectal or transperineal
      approach. Although the long-term effectiveness of focal therapy for prostate
      cancer is unknown, the effect on urinary or sexual function is extremely low.
      These procedures are attracting an increasing number of men who view focal
      therapies as a better alternative to the uncertainty of no therapy and the more
      radical whole-gland surgical and radiation therapies with their higher
      complication rates.

PMID- 30240325
TI  - Reply to "Radiology Resident Supervision".

PMID- 30240326
TI  - New Approaches to the Management of Adult Acute Lymphoblastic Leukemia.
AB  - Traditional treatment regimens for adult acute lymphoblastic leukemia, including
      allogeneic hematopoietic cell transplantation, result in an overall survival of
      approximately 40%, a figure hardly comparable with the extraordinary 80% to 90%
      cure rate currently reported in children. When translated to the adult setting,
      modern pediatric-type regimens improve the survival to approximately 60% in young
      adults. The addition of tyrosine kinase inhibitors for patients with Philadelphia
      chromosome-positive disease and the measurement of minimal residual disease to
      guide risk stratification and postremission approaches has led to additional
      improvements in outcomes. Relapsed disease and treatment toxicity-sparing no
      patient but representing a major concern especially in the elderly-are the most
      critical current issues awaiting further therapeutic advancement. Recently, there
      has been considerable progress in understanding the disease biology, specifically
      the Philadelphia-like signature, as well as other high-risk subgroups. In
      addition, there are several new agents that will undoubtedly contribute to
      additional improvement in the current outcomes. The most promising agents are
      monoclonal antibodies, immunomodulators, and chimeric antigen receptor T cells,
      and, to a lesser extent, several new drugs targeting key molecular pathways
      involved in leukemic cell growth and proliferation. This review examines the
      evidence supporting the increasing role of the new therapeutic tools and
      treatment options in different disease subgroups, including frontline and
      relapsed or refractory disease. It is now possible to define the best individual
      approach on the basis of the emerging concepts of precision medicine.

PMID- 30240329
TI  - ACHATINA FULICA (MOLLUSCA: ACHATINIDAE) NATURALLY INFECTED WITH CAENORHABDITIS
      BRIGGSAE (Dougherty & Nigon, 1949) (NEMATODA: RHABDITIDAE)).
AB  - Exemplars of the African snail Achatina fulica, collected in Bucaramanga,
      Colombia were examined for parasites. In the digestive tract, numerous specimens
      of Caenorhabditis briggsae were collected and identified by molecular and
      morphological methods. A redescription of the species is done.

PMID- 30240327
TI  - Multicenter Phase II Study of Lurbinectedin in BRCA-Mutated and Unselected
      Metastatic Advanced Breast Cancer and Biomarker Assessment Substudy.
AB  - PURPOSE: This multicenter phase II trial evaluated lurbinectedin (PM01183), a
      selective inhibitor of active transcription of protein-coding genes, in patients
      with metastatic breast cancer. A unicenter translational substudy assessed
      potential mechanisms of lurbinectedin resistance. PATIENTS AND METHODS: Two arms
      were evaluated according to germline BRCA1/2 status: BRCA1/2 mutated (arm A; n =
      54) and unselected ( BRCA1/2 wild-type or unknown status; arm B; n = 35).
      Lurbinectedin starting dose was a 7-mg flat dose and later, 3.5 mg/m2 in arm A.
      The primary end point was objective response rate (ORR) per Response Evaluation
      Criteria in Solid Tumors (RECIST). The translational substudy of resistance
      mechanisms included exome sequencing (n = 13) and in vivo experiments with
      patient-derived xenografts (n = 11) from BRCA1/2-mutated tumors. RESULTS: ORR was
      41% (95% CI, 28% to 55%) in arm A and 9% (95% CI, 2% to 24%) in arm B. In arm A,
      median progression-free survival was 4.6 months (95% CI, 3.0 to 6.0 months), and
      median overall survival was 20.0 months (95% CI, 11.8 to 26.6 months). Patients
      with BRCA2 mutations showed an ORR of 61%, median progression-free survival of
      5.9 months, and median overall survival of 26.6 months. The safety profile
      improved with lurbinectedin dose adjustment to body surface area. The most common
      nonhematologic adverse events seen at 3.5 mg/m2 were nausea (74%; grade 3, 5%)
      and fatigue (74%; grade 3, 21%). Neutropenia was the most common severe
      hematologic adverse event (grade 3, 47%; grade 4, 10%). Exome sequencing showed
      mutations in genes related to the nucleotide excision repair pathway in four of
      seven tumors at primary or acquired resistance and in one patient with short-term
      stable disease. In vivo, sensitivity to cisplatin and lurbinectedin was evidenced
      in lurbinectedin-resistant (one of two) and cisplatin-resistant (two of three)
      patient-derived xenografts. CONCLUSION: Lurbinectedin showed noteworthy activity
      in patients with BRCA1/2 mutations. Response and survival was notable in those
      with BRCA2 mutations. Additional clinical development in this subset of patients
      with metastatic breast cancer is warranted.

PMID- 30240328
TI  - Longitudinal Trajectory and Characterization of Cancer-Related Cognitive
      Impairment in a Nationwide Cohort Study.
AB  - PURPOSE: Cancer-related cognitive impairment (CRCI) is an important clinical
      problem in patients with breast cancer receiving chemotherapy. Nationwide
      longitudinal studies are needed to understand the trajectory and severity of CRCI
      in specific cognitive domains. PATIENTS AND METHODS: The overall objective of
      this nationwide, prospective, observational study conducted within the National
      Cancer Institute Community Clinical Oncology Research Program was to assess
      trajectories in specific cognitive domains in patients with breast cancer (stage
      I-IIIC) receiving chemotherapy, from pre- (A1) to postchemotherapy (A2) and from
      prechemotherapy to 6 months postchemotherapy (A3); controls were assessed at the
      same time-equivalent points. The primary aim assessed visual memory using the
      Cambridge Neuropsychological Test Automated Battery Delayed Match to Sample test
      by longitudinal mixed models including A1, A2, and A3 and adjusting for age,
      education, race, cognitive reserve score, and baseline anxiety and depressive
      symptoms. We also assessed trajectories of CRCI in other aspects of memory as
      well as in attention and executive function with computerized, paper-based, and
      telephone-based cognitive tests. RESULTS: In total, 580 patients with breast
      cancer (mean age, 53.4 years) and 363 controls (mean age, 52.6 years) were
      assessed. On the Delayed Match to Sample test, the longitudinal mixed model
      results revealed a significant group-by-time effect ( P < .005); patients
      declined over time from prechemotherapy (A1) to 6 months postchemotherapy (A3; P
      = .005), but controls did not change ( P = .426). The group difference between
      patients and controls was also significant, revealing declines in patients but
      not controls ( P = .017). Several other models of computerized, standard, and
      telephone tests indicated significantly worse performance by patients compared
      with controls from pre- to postchemotherapy and from prechemotherapy to 6 months
      postchemotherapy. CONCLUSION: This nationwide study showed CRCI in patients with
      breast cancer affects multiple cognitive domains for at least 6 months
      postchemotherapy.

PMID- 30240330
TI  - Primary versus secondary prevention messages: College students' perceptions of
      effectiveness by marijuana user status.
AB  - OBJECTIVE: With medical and recreational marijuana legislation expanding
      throughout the country, the need to educate high-risk populations is evident. The
      purpose of this study was to assess college students' perceptions of health
      communication messages comparing primary and secondary prevention messages
      concerning marijuana. PARTICIPANTS: Participants (n = 487) included college
      students, ages 18-25, enrolled in a Midwestern University. METHODS: Participants
      assessed messages based on likeability, creativity, believability,
      persuasiveness, relevance, and usefulness using an online questionnaire that also
      included open-end comments. RESULTS: Rasch analyses indicate that nonmarijuana
      users rated primary prevention messages higher than secondary prevention
      messages, whereas marijuana users ranked secondary prevention messages more
      favorably than primary prevention messages. CONCLUSION: Interventions designed to
      address marijuana use among college students may be more effective if tailored
      toward user status. Specifically, primary prevention materials should be designed
      for abstainers, while secondary prevention messages that focus on harm reduction
      strategies should be used with marijuana users.

PMID- 30240331
TI  - Computer self-administered screening for substance use in university student
      health centers.
AB  - OBJECTIVE: To characterize the prevalence of tobacco, alcohol, and drug use and
      the acceptability of screening in university health centers. PARTICIPANTS: Five
      hundred and two consecutively recruited students presenting for primary care
      visits in February and August, 2015, in two health centers. METHODS: Participants
      completed anonymous substance use questionnaires in the waiting area, and had the
      option of sharing results with their medical provider. We examined screening
      rates, prevalence, and predictors of sharing results. RESULTS: Past-year use was
      31.5% for tobacco, 67.1% for alcohol (>4 drinks/day), 38.6% for illicit drugs,
      and 9.2% for prescription drugs (nonmedical use). A minority (43.8%) shared
      screening results. Sharing was lowest among those with moderate-high risk use of
      tobacco (OR =0.37, 95% CI 0.20-0.69), alcohol (OR =0.48, 95% CI 0.25-0.90), or
      illicit drugs (OR =0.38, 95% CI 0.20-0.73). CONCLUSIONS: Screening can be
      integrated into university health services, but students with active substance
      use may be uncomfortable discussing it with medical providers.

PMID- 30240332
TI  - Orexigenic action of oral zinc: metabolomic analysis in the rat hypothalamus.
AB  - We previously reported an orexigenic action of oral zinc administration in male
      Sprague-Dawley (SD) rats during an early stage of feeding with a zinc-deficient
      diet, without decreased zinc concentrations in tissues. The overall conclusion
      was that orally but not intraperitoneally administered zinc stimulates food
      intake in short-term zinc-deficient-diet fed rats. We here investigate the
      mechanism of the orexigenic action of zinc using GC-MS/MS-targeted metabolomic
      analysis in the rat hypothalamus. Four-week-old, male SD/Slc rats were used, and
      after 2 days of feeding with a zinc-deficient diet, 3 mg of ZnSO4 in 5 mL saline
      solution were administered to each rat either orally or intraperitoneally. Three
      hours after administration, the rats were sacrificed and the hypothalamus were
      excised and analyzed. We found that the oral administration group showed
      increased concentrations of 3-aminopropanoic acid (beta-alanine), hypotaurine,
      dopamine, and biotin. In light of metabolomic analysis of these results, we
      indicate directions for further research.

PMID- 30240333
TI  - What is the most useful tool in HPV vaccine promotion? Results from an
      experimental study.
AB  - INTRODUCTION: Human papillomavirus infection (HPV) affects 70-80% of female
      population throughout the lifetime, exposing them to the risk of developing
      genital warts and cervical cancer. Despite these correlated risks and the
      demonstrated efficacy of the vaccine, coverage rates for two-three doses are
      around 70% in Italy and 67% in Piemonte (below the expected 95%). Aim of the
      study is to investigate whether this situation is due to a lack of information
      and awareness among young adults. RESULTS: Students showed increased knowledge
      after the intervention and more than 90% found the 3 informative materials as
      sources of useful information. After the intervention students would strongly
      recommend HPV vaccination (OR = 3.45; p < 0.001). DISCUSSION: Higher rates of
      correct answers after the distribution of informative material underline the
      importance of knowledge delivery. Differences among the kind of material were
      reported; it appears that a combination of leaflet's positive features, such as
      clarity and intelligibility, and article's completeness of information represents
      the best solution to reach communication goals in vaccination campaigns targeted
      on educated populations. METHODS: Researchers conducted an experimental study on
      a large population of undergraduate students from University of Turin.
      Participants' knowledge about HPV was assessed with questionnaires before and
      after the examination of 3 different kinds of informative material (journal
      article describing HPV infection, gynecologist video-interview and institutional
      leaflet about HPV prevention) on HPV and vaccine. Differences among groups were
      explored by using univariate tests, differences in pre- post- knowledge were
      assessed with McNemar tests. Relevant associations were searched with logistic
      regression models.

PMID- 30240334
TI  - Novel diversity in Lactifluus section Gerardii from Asia: five new species with
      pleurotoid or small agaricoid basidiocarps.
AB  - The ectomycorrhizal milkcap genus Lactifluus (Russulaceae) is commonly found in
      tropical and subtropical forests of Southeast Asia. During several sampling
      expeditions in Thailand, multiple collections of Lactifluus (Lf.) species with
      pleurotoid or small agaricoid basidiocarps were found. A molecular study was
      combined with a morphological study, in which the collections were compared with
      herbarium material. The molecular study indicated that four Thai collections
      belonged to undescribed species within Lactifluus section Gerardii, as was also
      the case for herbarium collections of a pleurotoid species from Nepal. One other
      collection from Thailand appeared closely related to Lf. uyedae, known only from
      Japan. Five species are described as new in the genus: Lf. auriculiformis, Lf.
      gerardiellus, Lf. bhandaryi, Lf. pulchrellus, and Lf. raspei.

PMID- 30240335
TI  - Does Transcranial Direct Current Stimulation Affect the Learning of a Fine
      Sequential Hand Motor Skill with Motor Imagery?
AB  - Learning a fine sequential hand motor skill, like playing the piano or learning
      to type, improves not only due to physical practice, but also due to motor
      imagery. Previous studies revealed that transcranial direct current stimulation
      (tDCS) and motor imagery independently affect motor learning. In the present
      study, we investigated whether tDCS combined with motor imagery above the primary
      motor cortex influences sequence-specific learning. Four groups of participants
      were involved: an anodal, cathodal, sham stimulation, and a control group
      (without stimulation). A modified discrete sequence production (DSP) task was
      employed: the Go/NoGo DSP task. After a sequence of spatial cues, a response
      sequence had to be either executed, imagined, or withheld. This task allows to
      estimate both non-specific learning and sequence-specific learning effects by
      comparing the execution of unfamiliar sequences, familiar imagined, familiar
      withheld, and familiar executed sequences in a test phase. Results showed that
      the effects of anodal tDCS were already developing during the practice phase,
      while no effects of tDCS on sequence-specific learning were visible during the
      test phase. Results clearly showed that motor imagery itself influences sequence
      learning, but we also revealed that tDCS does not increase the influence of motor
      imagery on sequence learning.

PMID- 30240336
TI  - College students' peer-helping behaviors and stigma of seeking help: Testing a
      moderated mediation model.
AB  - OBJECTIVE: College students are most likely to seek psychological help from their
      peers. Internalized public stigma (ie, personal stigma) may prevent peer-helpers
      from aiding others, and such help-negating effects may depend on contextual
      factors such as race and gender. The current study examined a moderated mediation
      model in which the relationship between public stigma and peer intervention
      behaviors was mediated by personal stigma and moderated by race and gender
      categories. METHOD: Undergraduate students (N = 5,183) from the national Healthy
      Minds Study completed measures of help-seeking stigma and peer-helping behaviors.
      RESULTS: Conditional Process Modeling revealed that personal stigma fully
      mediated the link between public stigma and peer-helping behaviors. Gender (but
      not race) moderated these associations such that the indirect and direct effects
      were stronger from men than women. CONCLUSIONS: Peer-helper interventions may
      benefit from culture-specific re-norming messages and by addressing the role of
      gender in peer-helping.

PMID- 30240337
TI  - College students' use of transportation networking companies: An opportunity to
      decrease substance-impaired driving.
AB  - OBJECTIVE: To examine the use of transportation networking companies (TNCs) (eg,
      Uber) among substance-using students in rural and urban college settings.
      PARTICIPANTS: Students at two large state universities were randomly selected and
      screened for substance use. Participants reported use of TNCs generally and after
      substance use and whether TNC use was on or near campus or in other environments.
      METHODS: Data were evaluated using chi-square test, t-tests, and Fisher's exact
      tests. RESULTS: Most (85%) participants (n = 99, 61% response rate) had used a
      TNC. Among students who used TNCs on/near campus, 98% of rural students used them
      after substance use compared to 85% of urban students (p = .037). We did not
      detect differences in TNC use by gender or age. CONCLUSIONS: Results indicate
      that TNC use is common after college student substance use and may play a
      particularly important role in preventing impaired driving for rural campuses
      where existing transportation options are limited.

PMID- 30240338
TI  - Taxonomy and phylogeny of Pyrrhoderma: a redefinition, the segregation of
      Fulvoderma, gen. nov., and identifying four new species.
AB  - Previously, Pyrrhoderma accommodated two polypore species, P. adamantinum and P.
      scaurum; however, phylogenetic studies indicated that these two species were not
      congeneric within the Hymenochaetaceae and that P. adamantinum formed a clade
      with Phellinidium noxium. To resolve the relationships among the two species of
      Pyrrhoderma and other related taxa, specimens from China, Costa Rica, Singapore,
      and Thailand were studied from both morphological and phylogenetic perspectives.
      A new genus, Fulvoderma, is erected to accommodate F. scaurum comb. nov., and a
      new species, F. australe (the generic type). Pyrrhoderma is delimited to include
      the generic type, P. sendaiense (a later synonym of P. adamantinum); two new
      combinations, P. lamaense comb. nov., and P. noxium comb. nov.; and three new
      species, P. hainanense, P. thailandicum, and P. yunnanense. In addition, an
      undescribed lineage including several specimens from subtropical and tropical
      forests in China, Costa Rica, Singapore, and Thailand also nested within the
      Pyrrhoderma clade. However, as the voucher specimens are sterile or almost so,
      they are not described. The concept of Pyrrhoderma was emended to also
      accommodate species bearing resupinate, effuse-reflexed basidiocarps, hymenial or
      hyphoid setae, and non-subglobose basidiospores. Keys to Fulvoderma and
      Pyrrhoderma are provided.

PMID- 30240339
TI  - Ethyl beta-d-glucoside: a novel chemoattractant of Ralstonia solanacearum
      isolated from tomato root exudates by a bioassay-guided fractionation.
AB  - A chemoattractant of Ralstonia solanacearum isolated from the activated charcoal
      adsorbed fraction of tomato root exudates was identified as ethyl beta-d
      glucopyranoside by instrumental analyses and comparison with synthetic
      preparations. Ethyl beta-D-glucopyranoside showed unambiguous activity at above 1
      umol/disc. Its stereoisomers and D-glucose were inactive.

PMID- 30240340
TI  - A systematic revision of the ectomycorrhizal genus Laccaria from Korea.
AB  - Species of Laccaria (Hydnangiaceae, Basidiomycota) are important in forest
      ecosystems as ectomycorrhizal fungi. Nine of the 75 described Laccaria species
      worldwide been reported from Korea. Most of these have European and North
      American names, and their identities are based solely on morphological features.
      To evaluate the taxonomy of Korean Laccaria, we used 443 specimens collected
      between 1981 and 2016 in a phylogenetic analysis based on sequence data from nuc
      rDNA internal transcribed spacer ITS1-5.8S-ITS2 rDNA (ITS) region, nuc 28S rDNA
      (28S), RNA polymerase II subunit 2 (rpb2), and translation elongation factor 1
      alpha (tef1). Ten Laccaria species were identified. Three of these were
      previously reported from Korea: L. bicolor, L. tortilis, and L. vinaceoavellanea.
      Laccaria alba, L. japonica, and L. murina are confirmed as new reports from
      Korea. Lastly, four new Laccaria species are described: L. araneosa, L. parva, L.
      torosa, and L. versiforma. This study supports the general contention that Asian
      species of ectomycorrhizal fungi may not be conspecific with morphologically
      similar species from Europe and North America. Furthermore, identification based
      on morphology alone is often unreliable in Laccaria due to considerable overlap
      of characters among species. Thus, use of molecular methods is necessary for
      effective identification. Illustrations of the four newly described species and a
      taxonomic key to species of Laccaria in Korea are provided.

PMID- 30240341
TI  - Peltaster gemmifer: A new species in the sooty blotch and flyspeck species
      complex from the United States.
AB  - Sooty blotch and flyspeck (SBFS) fungi infect the cuticle of fruit, including
      apple fruit, and produce pigmented colonies. A new member of this fungal complex
      in the genus Peltaster is described on the basis of molecular and morphological
      evidence. The SBFS complex is a diverse group of ectophytic fungi that reside
      primarily within the order Capnodiales. Sooty blotch and flyspeck isolates from
      apple orchards in the central United States were subjected to parsimony and
      Bayesian analyses based on the internal transcribed spacer regions of nuc rDNA,
      the partial translation elongation factor 1-alpha gene, and the partial
      mitochondrial small subunit rRNA gene. Phylogenetic analysis delineated a new
      species, Peltaster gemmifer, from P. cerophilus and P. fructicola. Peltaster
      gemmifer conidiophores bear primary conidia that produce secondary conidia either
      through budding or through microcyclic conidiation; these were not seen in
      cultures of P. cerophilus and P. fructicola. On cellulose membrane that was
      placed on water agar amended with apple juice, P. gemmifer produced brown to
      black pycnothyria in a superficial brownish mycelial mat, similar to the colonies
      produced on apple fruit. Findings from the present study add to the >80 named and
      putative SBFS species so far described worldwide.

PMID- 30240343
TI  - Discovery of a second species of Hyalocylindrophora and the phylogenetic position
      of the genus in Bionectriaceae.
AB  - A new holomorphic species, Hyalocylindrophora bispora, is described and
      illustrated based on a collection on rotten branches from Guangdong Province,
      China. The fungus is characterized by fleshy perithecia that become deeply
      cupulate when dry, covered with long and stiff hairs on the surface, and not
      change color in KOH or lactic acid. Asci are two-spored and evanescent at
      maturity. Ascospores are ellipsoidal to elongate-ellipsoidal, unicellular, and
      warted. Conidiogenous cells are phialidic and cylindrical. Conidia are thick
      walled, unicellular, ellipsoidal to somewhat lemon-shaped. This is the first
      report of sexual state for Hyalocylindrophora. The phylogenetic position of the
      genus in Bionectriaceae is confirmed by sequence analyses of the combined nuc
      rDNA 28S, alpha-actin, and DNA-directed RNA polymerase II subunit 1 regions.
      Distinctions between the new taxon and the only known species of the genus are
      compared.

PMID- 30240344
TI  - Comparative genomic analysis of the human and nematode Caenorhabditis elegans
      uncovers potential reproductive genes and disease associations in humans.
AB  - Reproduction is an important biological process. However, studies of human
      reproduction at the molecular level are limited due to the difficulty of
      performing in vivo studies. Hence, a mechanistic understanding of human
      reproduction remains still poor. Thus, it is important to use an alternative
      model organism for mechanistic studies of human reproduction. In this study, we
      used the nematode Caenorhabditis elegans as a model for studying human
      reproduction and identified 61 human and 535 worm reproductive genes through a
      combination of comparative genomic and Gene Ontology (GO) analyses.
      Interestingly, in terms of sex specificity, the number of male-specific genes was
      greater than the number of female-specific genes. Gene enrichment analysis
      identified biologically significant processes such as protein localization to
      cajal bodies/telomeres/nuclear bodies/chromosomes, helicase activity, pyrimidine
      biosynthesis and determination of adult lifespan. Regarding the analysis of human
      reproductive diseases among the identified genes, 10 and 12 genes were identified
      in the human- and C. elegans-based analyses, respectively. In addition, RNAi
      knockdown of a newly identified F52H2.6/DHCR24 gene increased brood size and
      ovulation/egg-laying rate in C. elegans. Therefore, gene identification, disease
      associations and a proof-of-concept experiment using C. elegans will not only
      provide insights into mechanistic study of human reproduction, but also
      demonstrate the utility in studying human reproduction.

PMID- 30240342
TI  - Parents' attitudes toward consent and data sharing in biobanks: A multisite
      experimental survey.
AB  - BACKGROUND: The factors influencing parents' willingness to enroll their children
      in biobanks are poorly understood. This study sought to assess parents'
      willingness to enroll their children, and their perceived benefits, concerns, and
      information needs under different consent and data-sharing scenarios, and to
      identify factors associated with willingness. METHODS: This large, experimental
      survey of patients at the 11 eMERGE Network sites used a disproportionate
      stratified sampling scheme to enrich the sample with historically
      underrepresented groups. Participants were randomized to receive one of three
      consent and data-sharing scenarios. RESULTS: In total, 90,000 surveys were mailed
      and 13,000 individuals responded (15.8% response rate). 5737 respondents were
      parents of minor children. Overall, 55% (95% confidence interval 50-59%) of
      parents were willing to enroll their youngest minor child in a hypothetical
      biobank; willingness did not differ between consent and data-sharing scenarios.
      Lower educational attainment, higher religiosity, lower trust, worries about
      privacy, and attitudes about benefits, concerns, and information needs were
      independently associated with less willingness to allow their child to
      participate. Of parents who were willing to participate themselves, 25% were not
      willing to allow their child to participate. Being willing to participate but not
      willing to allow one's child to participate was independently associated with
      multiple factors, including race, lower educational attainment, lower annual
      household income, public health care insurance, and higher religiosity.
      CONCLUSIONS: Fifty-five percent of parents were willing to allow their youngest
      minor child to participate in a hypothetical biobank. Building trust, protecting
      privacy, and addressing attitudes may increase enrollment and diversity in
      pediatric biobanks.

PMID- 30240345
TI  - Adverse Early Life Environment Induces Anxiety-like Behavior and Increases
      Expression of FKBP5 mRNA Splice Variants in Mouse Brain
AB  - Adverse early life environment (AELE) predisposes adult offspring towards 35
      anxiety disorders. Anxiety disorders are associated with prenatal injuries in key
      regions 36 of the brain including prefrontal cortex (PFC), hippocampus (HP) and
      hypothalamus 37 (HT). Injuries in these brain regions result in an impaired
      hypothalamus-pituitary-38 adrenal axis (HPA axis) and stress response. An
      important regulator of the stress 39 response is FK506-binding protein 5 (FKBP5).
      FKBP5 is a co-chaperone of the 40 glucocorticoid receptor (GR) and inhibits GR
      mediated regulatory feed-back on the HPA 41 axis in response to stress. Human
      studies have shown that polymorphisms of FKBP5 42 are associated with higher
      FKBP5 levels. Increased KFBP5 leads to GR resistance and 43 impaired negative
      feedback which is associated with anxiety disorders. FKBP5 and its 44 mRNA splice
      variants in the aforementioned brain regions have not been reported. We 45
      hypothesized that AELE will increase expression of FKBP5 and its mRNA splice 46
      variants in PFC, HP, and HT as well as increase anxiety in adult mice. AELE
      increased 47 expression of FKBP5 and its mRNA variants in PFC, HP and HT at
      postnatal day 21. 48 Additionally, AELE caused anxiety and increased GR abundance
      in association with 49 these changes in FKBP5 expression. We speculate that these
      changes in FKBP5 50 mRNA variants affect HPA axis function and contributes to
      subsequent anxiety-like 51 behavior later in life in AELE mice.

PMID- 30240346
TI  - The Epigenetics of Metabolic Syndrome.
AB  - The dramatic increase in global prevalence of metabolic disease is inexplicable
      when considering only environmental or only genetic factors, leading to the need
      to explore the possible roles of epigenetic factors. A great deal of progress has
      been made in this interdisciplinary field in recent years, with many studies
      investigating various aspects of the metabolic syndrome and its associated
      epigenetic changes. Rodent models of metabolic diseases have been particularly
      illuminating due to the ability to leverage tools such as genetic and
      environmental modifications. The current review summarizes recent breakthroughs
      regarding epigenetic markers in studies of obesity, type II diabetes, and
      cardiovascular disease, the three major disorders associated with metabolic
      syndrome. We also discuss open questions and future directions for integrating
      genomic, epigenomic, and phenotypic big bio-data towards understanding metabolic
      syndrome etiology.

PMID- 30240347
TI  - Identification of differentially expressed genes in broiler offspring under
      maternal folate deficiency.
AB  - Folate plays an important role in DNA and RNA synthesis by donating methyl
      groups. To investigate the effects of maternal folate deficiency (FD) on the
      abdominal adipose transcriptome, and on the accumulation of lipid droplets in the
      liver tissue of chicken offspring, differentially expressed genes (DEGs) of FD
      were identified with digital gene expression tag profiling. Ultramicroscopy
      suggested that the size of lipid droplets in hepatocytes increased with FD, while
      the lipid droplets population number was largely not affected. The serum
      parameters assay showed that the concentrations of MTHFR (476.57 vs 395.27), DHFR
      (45.056 vs 38.952), LPL (50.408 vs 48.677), HCY (4.354 vs 3.836), LEP (9.951vs
      8.673) and IGF2 (1209.4 vs 1027.7) in offspring serum of the FD group were
      significantly higher than those of the normal folate (NF) group (P < 0.01). The
      442 DEGs between NF and FD groups were identified using digital gene expression
      profiling. Considering the DEGs in the FD groups versus NF groups, 179 genes were
      up-regulated while 263 down-regulated, and in particular, 145 up-regulated and
      214 down-regulated DEGs were successfully annotated using the nr database. Gene
      Ontology analysis showed that FD mainly affected cellular processes, cell part
      and binding, cell killing, virions and receptor regulator activity. With pathway
      analysis, it indicated that 123 unigenes were assigned to 115 KEGG pathways, but
      only 5 of 115 these pathways were significantly enriched with P-values <= 0.05.
      Taken together, these results provide a foundation for further studying the
      responses of offspring to maternal FD in breeding chickens.

PMID- 30240348
TI  - 9.4T MR microscopy of the substantia nigra with pathological validation in
      controls and disease.
AB  - BACKGROUND: The anatomy of the substantia nigra on conventional MRI is
      controversial. Even using histological techniques it is difficult to delineate
      with certainty from surrounding structures. We sought to define the anatomy of
      the SN using high field spin-echo MRI of pathological material in which we could
      study the anatomy in detail to corroborate our MRI findings in controls and
      Parkinson's disease and progressive supranuclear palsy. METHODS: 23 brains were
      selected from the Queen Square Brain Bank (10 controls, 8 progressive
      supranuclear palsy, 5 Parkinson's disease) and imaged using high field 9.4Tesla
      spin-echo MRI. Subsequently brains were cut and stained with Luxol fast blue,
      Perls stain, and immunohistochemistry for substance P and calbindin. Once the
      anatomy was defined on histology the dimensions and volume of the substantia
      nigra were determined on high field magnetic resonance images. RESULTS: The
      anterior border of the substantia nigra was defined by the crus cerebri. In the
      medial half it was less distinct due to the deposition of iron and the
      interdigitation of white matter and the substantia nigra. The posterior border
      was flanked by white matter bridging the red nucleus and substantia nigra and
      seen as hypointense on spin-echo magnetic resonance images. Within the substantia
      nigra high signal structures corresponded to confirmed nigrosomes. These were
      still evident in Parkinson's disease but not in progressive supranuclear palsy.
      The volume and dimensions of the substantia nigra were similar in Parkinson's
      disease and controls, but reduced in progressive supranuclear palsy. CONCLUSIONS:
      We present a histologically validated anatomical description of the substantia
      nigra on high field spin-echo high resolution magnetic resonance images and were
      able to delineate all five nigrosomes. In accordance with the pathological
      literature we did not observe changes in the nigrosome structure as manifest by
      volume or signal characteristics within the substantia nigra in Parkinson's
      disease whereas in progressive supranuclear palsy there was microarchitectural
      destruction.

PMID- 30240349
TI  - Fronto-striatal glutamate in children with Tourette's disorder and attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: Both Tourette's disorder (TD) and attention-deficit/hyperactivity
      disorder (ADHD) have been related to abnormalities in glutamatergic
      neurochemistry in the fronto-striatal circuitry. TD and ADHD often co-occur and
      the neural underpinnings of this co-occurrence have been insufficiently
      investigated in prior studies. METHOD: We used proton magnetic resonance
      spectroscopy (1H-MRS) in children between 8 and 12years of age (TD n=15, ADHD
      n=39, TD+ADHD n=29, and healthy controls n=53) as an in vivo method of evaluating
      glutamate concentrations in the fronto-striatal circuit. Spectra were collected
      on a 3Tesla Siemens scanner from two voxels in each participant: the anterior
      cingulate cortex (ACC) and the left dorsal striatum. LC-model was used to process
      spectra and generate glutamate concentrations in institutional units. A one-way
      analysis of variance was performed to determine significant effects of diagnostic
      group on glutamate concentrations. RESULTS: We did not find any group differences
      in glutamate concentrations in either the ACC (F(3132)=0.97, p=0.41) or striatum
      (F(3121)=0.59, p=0.62). Furthermore, variation in glutamate concentration in
      these regions was unrelated to age, sex, medication use, IQ, tic, or ADHD
      severity. Obsessive-compulsive (OC) symptoms were positively correlated with ACC
      glutamate concentration within the participants with TD (rho=0.35,
      puncorrected=0.02). CONCLUSION: We found no evidence for glutamatergic
      neuropathology in TD or ADHD within the fronto-striatal circuits. However, the
      correlation of OC-symptoms with ACC glutamate concentrations suggests that
      altered glutamatergic transmission is involved in OC-symptoms within TD, but this
      needs further investigation.

PMID- 30240350
TI  - Distinct effects of childhood ADHD and cannabis use on brain functional
      architecture in young adults.
AB  - One of the most salient long-term implications of a childhood diagnosis of ADHD
      is an increased risk for substance use, abuse, or dependence in adolescence and
      adulthood. The extent to which cannabis use affects ADHD-related alterations in
      brain functional organization is unknown, however. To address this research gap,
      we recruited a sample of 75 individuals aged 21-25years with and without a
      childhood diagnosis of ADHD Combined Type, who were either frequent users or non
      users of cannabis. These participants have been followed longitudinally since age
      7-9.9years as part of a large multi-site longitudinal study of ADHD, the
      Multimodal Treatment Study of Children with ADHD (MTA). We examined task
      independent intrinsic functional connectivity (iFC) within 9 functional networks
      using a 2*2 design, which compared four groups of participants: (1) individuals
      with a childhood diagnosis of ADHD who currently use cannabis (n=23); (2)
      individuals with ADHD who do not currently use cannabis (n=22); (3) comparisons
      who currently use cannabis (n=15); and (4) comparisons who do not currently use
      cannabis (n=15). The main effects of childhood ADHD were primarily weakened iFC
      in networks supporting executive function and somatomotor control. Contrary to
      expectations, effects of cannabis use were distinct from those of diagnostic
      group and no interactions were observed. Exploratory brain-behavior analyses
      suggested that ADHD-related effects were primarily linked with poorer
      neurocognitive performance. Deficits in the integrity of functional networks
      supporting executive function and somatomotor control are consistent with the
      phenotypic and neurocognitive features of ADHD. Our data suggest that cannabis
      use does not exacerbate ADHD-related alterations, but this finding awaits
      replication in a larger sample. Longitudinal neuroimaging studies are urgently
      required to delineate the neurodevelopmental cascade that culminates in positive
      and negative outcomes for those diagnosed with ADHD in childhood.

PMID- 30240351
TI  - Metadata Correction: Conceptualization and Implementation of the Central
      Information Portal on Rare Diseases: Protocol for a Qualitative Study.
AB  - [This corrects the article DOI: 10.2196/resprot.7425.].

PMID- 30240352
TI  - Radiometal-labeled anti-VCAM-1 nanobodies as molecular tracers for
      atherosclerosis - impact of radiochemistry on pharmacokinetics.
AB  - Radiolabeling of nanobodies with radiometals by chelation has the advantage of
      being simple, fast and easy to implement in clinical routine. In this study, we
      validated 68Ga/111In-labeled anti-VCAM-1 nanobodies as potential radiometal-based
      tracers for molecular imaging of atherosclerosis. Both showed specific targeting
      of atherosclerotic lesions in ApoE-/- mice. Nevertheless, uptake in lesions and
      constitutively VCAM-1 expressing organs was lower than previously reported for
      the 99mTc-labeled analog. We further investigated the impact of different
      radiolabeling strategies on the in vivo biodistribution of nanobody-based
      tracers. Comparison of the pharmacokinetics between 68Ga-, 18F-, 111In- and 99mTc
      labeled anti-VCAM-1 nanobodies showed highest specific uptake for 99mTc-nanobody
      at all time-points, followed by the 68Ga-, 111In- and 18F-labeled tracer. No
      correlation was found with the estimated number of radioisotopes per nanobody,
      and mimicking specific activity of other radiolabeling methods did not result in
      an analogous biodistribution. We also demonstrated specificity of the tracer
      using mice with a VCAM-1 knocked-down phenotype, while showing for the first time
      the in vivo visualization of a protein knock-down using intrabodies.
      Conclusively, the chosen radiochemistry does have an important impact on the
      biodistribution of nanobodies, in particular on the specific targeting, but
      differences are not purely due to the tracer's specific activity.

PMID- 30240353
TI  - Dual frequency bioelectrical impedance analysis to estimate hematocrit for
      prognosis of dengue fever in Indian children.
AB  - A noninvasive investigation to ascertain the hematocrit (HCT) or packed cell
      volume (PCV) was conducted on 44 hospitalized dengue hemorrhagic fever (DHF)
      subjects, male and female aged between 3 and 14 years using bioelectrical
      impedance analysis (BIA). Among the 44 subjects, 30 subjects were confirmed to be
      non-structural protein-1 (NS1) positive at the time of admission, whose blood
      investigations such as HCT level, platelet (PLT) count, aspartate
      aminotransferase (AST) level and alanine aminotransferase (ALT) level were taken
      for the classification of risk as low risk (LR) and high risk (HR) DHF.
      Electrical conductivity of blood reflects a linear correlation with HCT. To
      provide a better and more accurate estimate of HCT, a dual frequency method is
      proposed to calculate the conductivities of plasma and blood cells. The
      resistance at 100 kHz is used to estimate the conductivity of blood cells and the
      impedance at 5 kHz to estimate the conductivity of plasma. Statistical analysis
      reveals that the HCT estimated using the proposed dual frequency method shows a
      significant difference with a single frequency (50 kHz) estimate of HCT and also
      shows a good correlation with the blood investigation results. In addition,
      statistical analysis of the proposed method on different fever subjects indicates
      a significant difference with DHF.

PMID- 30240354
TI  - Intraoperative motion correction in neurosurgery: a comparison of intensity- and
      feature-based methods.
AB  - The intraoperative identification of normal and anomalous brain tissue can be
      disturbed by pulsatile brain motion and movements of the patient and surgery
      devices. The performance of four motion correction methods are compared in this
      paper: Two intensity-based, applying optical flow algorithms, and two feature
      based, which take corner features into account to track brain motion. The target
      registration error with manually selected marking points and the temporal
      standard deviation of intensity were analyzed in the evaluation. The results
      reveal the potential of the two types of methods.

PMID- 30240355
TI  - Analyzing the capability of PSP, PCT and sCD25 to support the diagnosis of
      infection in cancer patients with febrile neutropenia.
AB  - Background Early diagnosis of infection is essential for the initial management
      of cancer patients with chemotherapy-associated febrile neutropenia (FN). In this
      study, we have evaluated two emerging infection biomarkers, pancreatic stone
      protein (PSP) and soluble receptor of interleukin 2, known as soluble cluster of
      differentiation 25 (sCD25), for the detection of an infectious cause in FN, in
      comparison with other commonly used infection biomarkers, such as procalcitonin
      (PCT). Methods A total of 105 cancer patients presenting to the emergency
      department were prospectively enrolled. We observed 114 episodes of chemotherapy
      associated FN. At presentation, a blood sample was collected for the measurement
      of PCT, PSP and sCD25. In order to evaluate the discriminatory ability of these
      markers for the diagnosis of infection, the area under the curve (AUC) of the
      receiver operating characteristic curves was calculated. Results Infection was
      documented in 59 FN episodes. PCT, PSP and sCD25 levels were significantly higher
      in infected patients. PCT was the biomarker with the highest diagnostic accuracy
      for infection (AUC: 0.901), whereas PSP and sCD25 showed a similar performance,
      with AUCs of 0.751 and 0.730, respectively. In a multivariable analysis, PCT and
      sCD25 were shown to be independently associated with infection. Conclusions Two
      novel biomarkers, PSP and sCD25, correlated with infection in cancer patients
      with chemotherapy-associated FN, but neither PSP nor sCD25 improved the
      performance of PCT. Based on the results obtained, the introduction of these
      novel biomarkers as a tool for the diagnosis of infection in this patient group
      is not recommended.

PMID- 30240356
TI  - MS-based proteomics: a metrological sound and robust alternative for
      apolipoprotein E phenotyping in a multiplexed test.

PMID- 30240357
TI  - "Closing the loop": a mixed-methods study about resident learning from outcome
      feedback after patient handoffs.
AB  - Background Learning patient outcomes is recognized as crucial for ongoing
      refinement of clinical decision-making, but is often difficult in fragmented care
      with frequent handoffs. Data on resident habits of seeking outcome feedback after
      handoffs are lacking. Methods We performed a mixed-methods study including (1) an
      analysis of chart re-access rates after handoffs performed using access logs of
      the electronic health record (EHR); and (2) a web-based survey sent to internal
      medicine (IM) and emergency medicine (EM) residents about their habits of and
      barriers to learning the outcomes of patients after they have handed them off to
      other teams. Results Residents on ward rotations were often able to re-access
      charts of patients after handoffs, but those on EM or night admitting rotations
      did so <5% of the time. Among residents surveyed, only a minority stated that
      they frequently find out the outcomes of patients they have handed off, although
      learning outcomes was important to both their education and job satisfaction.
      Most were not satisfied with current systems of learning outcomes of patients
      after handoffs, citing too little time and lack of reliable patient tracking
      systems as the main barriers. Conclusions Despite perceived importance of
      learning outcomes after handoffs, residents cite difficulty with obtaining such
      information. Systematically providing feedback on patient outcomes would meet a
      recognized need among physicians in training.

PMID- 30240358
TI  - Achieving target levels for vascular risk parameters in Polish school-age
      children with type 1 diabetes - a single center study.
AB  - Background Therapeutic goals have been established to decrease the risk of long
      term complications of type 1 diabetes (T1DM). The effects of these guidelines
      should be constantly evaluated. Hence, the present study examines the frequency
      at which children with T1DM treated by one of the Polish reference centers
      complied with the therapeutic targets issued in 2014 by the International Society
      for Pediatric and Adolescent Diabetes (ISPAD) and by the Diabetes Poland (PTD).
      Methods A retrospective analysis (years 2011-2014) was performed in patients with
      T1DM aged 6.5-18 years, with diabetes duration >12 months and no change of
      insulin regimen within 6 months. Collected data included insulin therapy regimen,
      weight, height, blood pressure, high-density lipoprotein cholesterol (HDL-C), low
      density lipoprotein cholesterol (LDL-C), triglycerides (TG) and glycated
      hemoglobin (HbA1c) level from the last hospitalization. Results The records of
      447 patients (260 boys, 299 treated with insulin pump) were analyzed. All ISPAD
      goals were achieved by 123 (27.5%) patients, but only 43 (9.6%) met all PTD
      targets. Optimal HbA1c was achieved by 224 (50.1%) according to ISPAD criteria
      (HbA1c<7.5%) and by 87 (19.6%) patients according to PTD (HbA1c<=6.5%). Obesity
      was diagnosed in 11.6% of the patients; 19.7% of the patients were overweight. In
      logistic regression, patient age was the only independent predictor of failing to
      achieve complete T1DM control (p=0.001, OR=1.12 [1.05-1.23]) and optimal HbA1c
      (p=0.01, OR=1.1 [1.0-1.2]) according to ISPAD guidelines. Moreover, girls had a
      greater risk of failing body mass index (BMI) targets (PTD: p=0.002, OR=2.16;
      ISPAD: p=0.0001, OR=3.37) and LDL-C targets (p=0.005, OR=1.8) than boys.
      Conclusions Overall, control of vascular risk factors in Polish children with
      T1DM is unsatisfactory. While too few children are achieving the HbA1c target set
      by PTD, it is possible that such strict national target helps half of the Polish
      school-age patients achieve ISPAD-issued aim which is more liberal. High
      prevalence of overweight among children with T1DM warrants initiatives focused
      not only on glycemic control but also on motivation of patients to lead a healthy
      lifestyle.

PMID- 30240359
TI  - Pain self-efficacy moderates the association between pain and somatization in a
      community sample.
AB  - Background and aims Pain is a common condition. However, only a minority of
      people experiencing pain develop a chronic pain problem. Factors such as
      somatization, pain self-efficacy and lack of psychological well-being affect the
      risk of pain chronicity and pain-related disability. However, research on
      protective pain-related psychological factors in populations without chronic pain
      is scarce. We aim to examine if pain self-efficacy attenuates the associations
      between pain and both anxiety and somatization in a community sample. Methods In
      a cross-sectional study, 211 participants from a community sample responded to
      measures of average pain over the last 3 months, anxiety, somatization, and pain
      self-efficacy. The possibility of moderation effects were tested with a series of
      regression analyses. Results The association between pain and anxiety was not
      moderated by pain self-efficacy. In contrast, pain self-efficacy moderated the
      relation of pain and somatization. The interaction explained 3% of the variance
      in somatization, in addition to the independent effects of pain and self-efficacy
      (F(1,207)=5.65, p<0.025). Among those in the bottom quartile of pain self
      efficacy, the association between pain and somatization was moderate or strong
      (r=0.62, p<0.01), whereas for those in the top quartile the association was
      modest (r=0.11, p>0.05). Conclusions The results are partly consistent with the
      hypothesis that pain self-efficacy attenuates the associations between pain and
      pain chronification risk factors in a relatively healthy community sample. Should
      further preferably longitudinal studies replicate the findings, the role pain
      self-efficacy as a protective factor needs to be explicated in theoretical models
      of pain chronification. Implications The findings are consistent with the notion
      that clinicians should promote patient's pain self-efficacy in acute and sub
      acute pain conditions especially when the individual is prone to somatization.
      However, more prominent clinical implications require studies with longitudinal
      designs.

PMID- 30240361
TI  - Modeling nanoscale temperature gradients and conductivity evolution in pulsed
      light sintering of silver nanowire networks.
AB  - Sintering of metal nanowire (NW) networks on transparent polymers is an emerging
      approach for fabricating transparent conductive electrodes used in multiple
      devices. Pulsed light sintering is a scalable sintering process in which large
      area, broad-spectrum xenon lamp light causes rapid NW fusion to increase network
      conductivity, while embedding the NWs in the polymer to increase mechanical
      robustness. This paper develops a multiphysical approach for predicting evolution
      of conductivity, NW fusion and nanoscale temperature gradients on the substrate
      during pulsed light sintering of silver NWs on polycarbonate. Model predictions
      are successfully validated against experimentally measured temperature and
      electrical resistance evolution. New insight is obtained into the diameter
      dependent kinetics of NW fusion and nanoscale temperature gradients on the
      substrate, which are difficult to obtain experimentally. These observations also
      lead to the understanding that NW embedding in intense pulsed light sintering
      (IPL) can occur below the glass transition temperature of the polymer, and to a
      new differential thermal expansion-based mechanism of NW embedding during IPL.
      These insights, and the developed model, create a framework for physics-guided
      choice of NWs, substrate and process parameters to control conductivity and
      prevent substrate damage during the process.

PMID- 30240360
TI  - Pediatric chronic pain and caregiver burden in a national survey.
AB  - Background and aims Caring for children with chronic pain incurs burdens of cost
      and time for families. We aimed to describe variation in caregiver burden among
      parents of adolescents with chronic pain who responded to a nationally
      representative survey. Our secondary aim was to identify child and parent
      characteristics associated with increased caregiver burden. Methods We used de
      identified, publicly-available data from the 2016 National Survey of Children's
      Health (NSCH), designed to be representative of non-institutionalized children in
      the United States. We analyzed data for households where an adolescent age 12-17
      years old was reported by a parent to have chronic pain. Outcomes included the
      parent's time spent on the child's health needs, reduced labor force
      participation, and out-of-pocket medical costs. Results Data on 1,711 adolescents
      were analyzed. For adolescents with chronic pain, 15% of parents reported
      spending at least 1 h/week on their child's health care, 14% reported cutting
      back on paid work, and 36% reported spending >=$500 on their child's health care
      in the past 12 months. Adolescents' general health status and extent of
      specialized health care needs predicted increased caregiver burden across the
      three measures. Conversely, no consistent differences in caregiver burden were
      noted according to demographic or socioeconomic characteristics. Conclusions
      Among adolescents with chronic pain identified on a nationally-representative
      survey, parents frequently reported reducing work participation and incurring out
      of-pocket expenses in providing health care for their child. Caregiver burdens
      increased with indicators of greater medical complexity (e.g. presence of
      comorbidities, need for specialized health care) and poorer overall adolescent
      health status. Implications We add a national-level perspective to studies
      previously performed in clinical samples addressing caregiver burden in pediatric
      chronic pain. Initiatives to reduce the burden of caring for children with
      chronic pain, described in prior work, may be especially beneficial for families
      with adolescents whose chronic pain is accompanied by other health problems or
      requires coordination of care among multiple providers.

PMID- 30240362
TI  - A simple route to synchronized nucleation of self-catalyzed GaAs nanowires on
      silicon for sub-Poissonian length distributions.
AB  - We demonstrate a simple route to grow ensembles of self-catalyzed GaAs nanowires
      with a remarkably narrow statistical distribution of lengths on natively oxidized
      Si(111) substrates. The fitting of the nanowire length distribution (LD) with a
      theoretical model reveals that the key requirements for narrow LDs are the
      synchronized nucleation of all nanowires on the substrate and the absence of beam
      shadowing from adjacent nanowires. Both requirements are fulfilled by controlling
      the size and number density of the openings in SiO x , where the nanowires
      nucleate. This is achieved by using a pre-growth treatment of the substrate with
      Ga droplets and two annealing cycles. The narrowest nanowire LDs are markedly sub
      Poissonian, which validates the theoretical predictions about temporally anti
      correlated nucleation events in individual nanowires, the so-called nucleation
      antibunching. Finally, the reproducibility of sub-Poissonian LDs attests the
      reliability of our growth method.

PMID- 30240363
TI  - Vertically-aligned graphene nanowalls grown via plasma-enhanced chemical vapor
      deposition as a binder-free cathode in Li-O2 batteries.
AB  - In the present report, vertically-aligned graphene nanowalls are grown on Ni foam
      (VA-G/NF) using plasma-enhanced chemical vapor deposition method at room
      temperature. Optimization of the growth conditions provides graphene sheets with
      controlled defect sites. The unique architecture of the vertically-aligned
      graphene sheets allows sufficient space for the ionic movement within the sheets
      and hence enhancing the catalytic activity. Further modification with ruthenium
      nanoparticles (Ru NPs) drop-casted on VA-G/NF improves the charge overpotential
      for lithium-oxygen (Li-O2) battery cycles. Such reduction we believe is due to
      the easier passage of ions between the perpendicularly standing graphene sheets
      thereby providing ionic channels.

PMID- 30240364
TI  - Dual-plasmonic Au/graphene/Au-enhanced ultrafast, broadband, self-driven silicon
      Schottky photodetector.
AB  - High-performance photodetectors are desirable for various applications, including
      multi-wavelength image sensing, communication, and safety monitoring. In this
      study, we report the construction of a dual-surface plasmon-enhanced silicon
      Schottky photodetector using Au nanoparticles (NPs)/graphene/Au NPs hybrid
      structure as the electrode. It was found that the as-assembled device exhibited
      broad sensitivity, ranging from ultraviolet to near-infrared light (360-1330 nm)
      at room temperature, with a high response speed of 360 ns and a 3 dB bandwidth of
      780 kHz at zero bias. Further theoretical simulation based on the finite-element
      method revealed that good device performance is associated with the contribution
      of the Au NPs/graphene/Au NPs electrode: intense dual-plasmonic resonance
      coupling is induced in a hybrid structure of two layers of metallic NPs separated
      by a uniform monolayer graphene. It not only can enhance light trapping and the
      localized electric field at the resonant and off-resonant wavelength regions, but
      is also beneficial for the tunneling of hot electrons. This work demonstrated the
      great potential of dual-plasmonic resonance coupling in optoelectronic devices
      and will lead to the development of advanced plasmonic devices.

PMID- 30240365
TI  - A three-dimensional insight into correlation between carrier lifetime and surface
      recombination velocity for nanowires.
AB  - The performance of nanowire-based devices is predominantly affected by
      nonradiative recombination on their surfaces, or sidewalls, due to large surface
      to-volume ratios. A common approach to quantitatively characterize surface
      recombination is to implement time-resolved photoluminescence to correlate
      surface recombination velocity with measured minority carrier lifetime by a
      conventional analytical equation. However, after using numerical simulations
      based on a three-dimensional (3D) transient model, we assert that the correlation
      between minority carrier lifetime and surface recombination velocity is dependent
      on a more complex combination of factors, including nanowire geometry, energy
      band alignment, and spatial carrier diffusion in 3D. To demonstrate this
      assertion, we use three cases-GaAs nanowires, InGaAs nanowires, and InGaAs
      inserts embedded in GaAs nanowires-and numerically calculate the carrier
      lifetimes by varying the surface recombination velocities. Using this
      information, we then investigate the intrinsic carrier dynamics within those 3D
      structures. We argue that the conventional analytical approach to determining
      surface recombination in nanowires is of limited applicability, and that a
      comprehensive computation in 3D can provide more accurate analysis. Our study
      provides a solid theoretical foundation to further understand surface
      characteristics and carrier dynamics for 3D nanostructured materials.

PMID- 30240366
TI  - Approaches for the quantitative analysis of oxidation state in cerium oxide
      nanomaterials.
AB  - Cerium oxide nanomaterials (nanoceria, CNMs) are receiving increased attention
      from the research community due to their unique chemical properties, most
      prominent of which is their ability to alternate between the Ce3+ and Ce4+
      oxidation states. While many analytical techniques and methods have been employed
      to characterize the amounts of Ce3+ and Ce4+ present (Ce3+/Ce4+ ratio) within
      nanoceria materials, to-date no studies have used multiple complementary
      analytical tools (orthogonal analysis) with technique-independent oxidation state
      controls for quantitative determinations of the Ce3+/Ce4+ ratio. Here, we
      describe the development of analytical methods measuring the oxidation states of
      nanoceria analytes using technique-independent Ce3+ (CeAlO3:Ge) and Ce4+ (CeO2)
      control materials, with a particular focus on X-ray photoelectron spectroscopy
      (XPS) and electron energy loss spectroscopy (EELS) approaches. The developed
      methods were demonstrated in characterizing a suite of commercial nanoceria
      products, where the two techniques (XPS and EELS) were found to be in good
      agreement with respect to Ce3+/Ce4+ ratio. Potential sources of artifacts and
      discrepancies in the measurement results were also identified and discussed,
      alongside suggestions for interpreting oxidation state results using the
      different analytical techniques. The results should be applicable towards
      producing more consistent and reproducible oxidation state analyses of nanoceria
      materials.

PMID- 30240367
TI  - Study of the growth mechanisms of nanoporous Ag flowers for non-enzymatic glucose
      detection.
AB  - Highly sensitive and selective non-enzymatic glucose detection was developed
      using nanoporous Ag flowers on a Ni substrate. The cyclic scanning
      electrodeposition (CSE) method was used to fabricate Ag flowers on a Ni substrate
      in an alkaline electrolyte. The nanoporous Ag flowers were then formed by
      repeated CSE in NaOH. The growth mechanisms of the nanoporous Ag flowers were
      systematically studied, and these mechanisms can be extended to the formation of
      other metal, bimetal or metal oxide. The synthesized three-dimensional nanoporous
      Ag flowers on the Ni substrate were used in the electro-oxidation of glucose,
      demonstrating a wide linear range (0.1 MUM to 1 mM), fast response time (<2 s),
      low detection limit of 0.1 MUM (S/N = 3) and a high sensitivity to detect glucose
      in the presence of uric acid (UA) and ascorbic acid (AA) at the level of their
      physiological concentrations. Apart from the nanoporous Ag flowers, the formation
      of a NiO thin layer on the Ni substrate during CSE also contributed to the high
      selectivity. This work indicates the potential for developing a fast, sensitive,
      selective and stable electrochemical sensor for diabetes diagnosis.

PMID- 30240368
TI  - [Cistus - queen of teas].
AB  - The aim of our article is to present a healthy qualities of Cistus. Cistus is
      plant belonging to the Cistaceae has strong health-promoting properties through
      its antioxidant, immunomodulatory, bacteriostatic and antifungal activities.
      Cistus has an inhibitory effect on the multiplication of viruses, which can be
      used to treat cold and influenza. A significant effect of the Cistus on stopping
      the growth and proliferation of prostatic cells was also demonstrated, which
      evidence of cytotoxic and antiproliferative activity. This activity can be used
      in both benign and malignant prostatic enlargement, as well as adjuvant in the
      treatment of other cancers. Extract from Cistus through modulation of immune
      system significantly strengthens immunity and has antiallergic activity. Cistus
      has a lot of polyphenols that destroy free radicals, inhibit the formation and
      development of inflammation in the body, strengthen, energize, and have a
      preventive effect on cardiovascular diseases. Through bioflavonoids, it works
      synergistically with vitamin C, enhancing its action, and also protects the
      mucous membrane of the stomach, preventing the formation of ulcers, or helping to
      treat them. Because of healing properties, as well as taste qualities the Cistus-
      teacan be boldly recommended as a daily drink for both young and old people. The
      promoting the use of infusion from a Cistus along with honey or lemon juice
      should be as wide as possible.

PMID- 30240369
TI  - Comparative assessment of limb function and conduction parameters in peripheral
      nerves in the course of two forms of amyotrophic lateral sclerosis.
AB  - : Amyotrophic lateral sclerosis (ALS) is a progressive, incurable,
      neurodegenerative disease affecting the upper and lower motor neuron, which
      inevitably leads to the impaired fitness of patients and therefore deterioration
      of their quality of life. AIM: The aim of the study was a comparative assessment
      of two forms of ALS in terms of limb function and electrophysiological parameters
      of peripheral nerves. MATERIALS AND METHODS: 20 persons participated in the
      study, where 10 suffered from bulbar-onset ALS and 10 had limb-onset ALS.
      Patients were examined clinically and electrophysiologically three times at three
      month intervals. Rene Zazzo's card test and Mira Stambak's line-drawing test as
      well as the 10-metre walk test were used to assess limb function. The results of
      electrophysiological conduction in the area of nerves of upper and lower limbs
      were subjected to statistical analysis, as were the results of tests used to
      assess limb function. RESULTS: The comparative analysis of the obtained results
      demonstrated that patients with limb-onset ALS showed significant deterioration
      of conduction in proximal nerve sections compared to patients with bulbaronset
      ALS. Clinical reflection of this was impairment of limb function with a tendency
      for progression of these changes over time. CONCLUSIONS: Progressive impairment
      of conduction in the area of proximal nerve sections and ventral roots of spinal
      nerves is reflected by the increasing disability of limbs in patients with ALS.
      In the course of the disease, patients with limb-onset ALS show both worse nerve
      conduction and limb function than patients with bulbar-onset ALS.

PMID- 30240370
TI  - [Non-psychotic mental disorders in professional soldiers hospitalized in the
      Department of Psychiatry of the 10th Military Clinical Hospital in Bydgoszcz].
AB  - : In the present analysis 60 professional soldiers who were patients at the
      Department of Psychiatry of the 10th Military Clinical Hospital in Bydgoszcz in
      the years 2015-2017 were analyzed. AIM: The aim of the work was to analyze non
      psychotic mental disorders of professional soldiers residing in the Department of
      Psychiatry. MATERIALS AND METHODS: The study was conducted in a group of 60
      patients, men, professional soldiers, in whom made one of the diagnoses, i.e.
      neurasthenia, post-traumatic stress disorder - PTSD, adaptive disorders and
      personality disorders. The analysis included biographical factors: age, military
      rank, military experience, marital status, education and previous psychiatric
      treatment, stays in psychiatric hospitals and taking part in missions. RESULTS:
      Among 60 soldiers hospitalized in the Department of Psychiatry the main mental
      and non-psychotic disorders were personality disorders (45%) and neurasthenia
      (43,4%). A small percentage was diagnosed with PTSD (8,3%) and adaptive disorders
      (3,3%). CONCLUSIONS: The analysis of non-psychotic psychiatric disorders among
      soldiers hospitalized in the Department of Psychiatry showed that the main
      diagnoses were personality disorders (45%) and neurasthenia.

PMID- 30240371
TI  - Takotsubo cardiomyopathy triggered by influenza B.
AB  - Influenza is associated with a high prevalence of cardiac complications,
      including myocarditis and exacerbation of ischemic heart disease or heart failure
      (HF). However, only four cases of stress-induced takotsubo cardiomyopathy (TC),
      all of them triggered by virus A influenza, have been reported so far. Another
      two TC cases after anti-influenza vaccination are also available in the
      literature. The authors describe a new case of TC, this time provoked by
      influenza B. An 89-year-old female with a history of hypertension and chronic
      obstructive pulmonary disease (COPD) was admitted due to a fever (39oC), muscle
      aches and cough. Pneumonia was excluded in chest X-ray while the test for
      influenza confirmed virus B infection, so she was given oseltamivir. On the
      second day of hospitalization, she developed severe HF. ECG showed new negative T
      waves in inferior and anterolateral leads coexisting with a moderate troponin I
      and marked brain natriuretic peptide release, while echocardiography revealed
      left ventricular (LV) apical ballooning with decreased ejection fraction (EF 24%)
      and global longitudinal strain (GLS -8.1%). Symptomatic treatment of HF was
      initiated. The symptoms of influenza resolved after 5 days. LV function began to
      improve after 4 days and became normal after 6 days (EF 58%, GLS -18.1%). Despite
      an advanced age and the coexisting disorders (COPD, mild cognitive impairment,
      possible neoplastic disease), the patient was discharged in stable clinical
      condition on day 10. The authors conclude that in the evaluation of cardiac
      complications of influenza, TC should be taken into account.

PMID- 30240372
TI  - [An amateur marathon runner after sudden cardiac arrest. Whether and when can he
      return to sport competition?]
AB  - Regular physical activity of low/moderate intensity is associated with numerous
      health-related benefits and, the most importantly, longer life. However, every
      second patient fails to achieve the suggested weekly dose of 2.5 hours of
      moderate physical activity. On the other hand, there is an increasing number of
      people who regularly overdose - marathons or triathlons competitors. While there
      are no clear data against amateurs' participation in long distance runs, more and
      more reports on the possible dangers of overdosing extreme endurance exercises
      appear. A case of an amateur runner has been presented, competitor in 50
      marathons, who underwent a sudden cardiac arrest while preparing for the next
      marathon run. Based on the current guidelines, we discuss the issue, whether and
      when a patient in whom an ICD was implanted, can return to sport competition.

PMID- 30240373
TI  - Patient with glossopharyngeal schwannoma of cerebellopontine angle.
AB  - We present a case of a man diagnosed with a rare tumour of cerebellopontine angle
      glossopharyngeal schwannoma. First symptoms started at the beginning of January
      2014, patient complained of tinnitus in his right ear. He had a magnetic
      resonance imaging (MRI) and it revealed a tumour of cerebellopontine angle. The
      patient underwent a surgery in September 2014. In this case tinnitus was the only
      symptoms of glossopharyngeal schwannoma. After surgery patient suffered from
      hoarseness and mild difficulty in swallowing. After analyzing the available
      literature it turned out that the symptoms of this tumor are not characteristic.

PMID- 30240374
TI  - [Sepsis - still valid economic and epidemiological problem].
AB  - The recognition of sepsis is connected with potentially bad prognosis, high
      mortality rate and high costs of the therapy. A new definition of sepsis was
      introduced in 2016. The main role of dysfunction of organs in the course of
      infection, the potential threat for life and necessity to perform quick diagnosis
      result from this definition. The review of worldwide literature on sepsis
      epidemiology and therapy costs was done in the current article. It was observed
      that the data concerning incidence of sepsis in Polish hospitals are incomplete,
      related to single observations, and in most cases they come from retrospective
      analyses. Therefore, the nation-wide registry comprising the data of the sepsis
      cases should be established.

PMID- 30240375
TI  - [Rational hypoglycemic therapy - nephro-diabetologic view].
AB  - Diabetes is a heterogenous group of diseases with chronic hyperglycemia, which is
      associated with the risk of many complications, including diabetic kidney
      disease. Micro- and macroangiopathy in hyperglycemic environment leads to organ
      failure, including end-stage renal disease, requiring dialysis or kidney
      transplantation. However, diabetes is not the only cause leading to kidney
      dysfunction in this patient population. A patient with diabetes should be
      monitored regularly for proteinuria and glomerular filtration rate and depending
      on advancement of kidney disease or suspicion other than diabetes cause of kidney
      damage, should also be covered by nephrological care. Appropriately selected
      hypoglycemic drugs and their doses, in combination with appropriate non
      pharmacological treatment, in the patients with different stages of kidney
      disease, not only reduces the risk of drug-induced side effects but, above all,
      may slow the progression of kidney damage and reduce the risk of other
      complications in this group of patients. Recently, there have been many new
      groups of hypoglycemic agents that can be used in the treatment of patients with
      kidney disease. The aim of this study is to present the current possibilities of
      hypoglycemic therapy in patients with different stages of chronic kidney disease.
      In addition, the relationship between individual groups of hypoglycemic agents
      and the renal benefits and risk was analyzed.

PMID- 30240376
TI  - [The importance of the kynurenine pathway in depressive disorders].
AB  - Depressive disorders are the most frequently diagnosed mental disorder. It is
      assumed that the etiology of depression is multifactorial and the individual
      theories complement each other. Referring to the neurochemical hypothesis of the
      underlying depressive disorder, the relationship between lowering levels of
      serotonin, norepinephrine, dopamine and a change in mood is suggested. Particular
      attention has been given to serotonin, called the happiness hormone, which is
      synthesized from the exogenous amino acid tryptophan. The main methods of
      antidepressant treatment, in particular the use of serotonin reuptake inhibitors
      (SSRIs), take into account the concept of monoamine deficiency in patients with
      depression. However, an insufficient response in some patients to antidepressants
      (the existence of a refractory depression), indicates the importance of looking
      for other possible causes for the development of this disease and thus
      alternative treatment methods. It is indicated that in patients with depression
      there are disorders of tryptophan metabolism, ie the redirection of tryptophan
      from the serotonin synthesis pathway to the kynurenine pathway, which is the
      source of neuroactive compounds in the central nervous system, so-called.
      kynurenin m.in. kynurenic acid, 3-hydroxycinurenine, quinoline acid. It has been
      proved that certain metabolites of this cycle of transformations have
      neuroprotective and other neurotoxic properties. For this reason, it seems
      reasonable to summarize the research published so far on this subject.

PMID- 30240377
TI  - [The role of high cut off membranes in renal replacement therapy of acute kidney
      injury in the course of sepsis - the current state of knowledge].
AB  - Sepsis as a systemic inflammatory reaction to infection is an important
      interdisciplinary clinical problem. Over the past 20 years, the number of
      patients who have contracted sepsis has doubled. The occurrence of acute kidney
      injury in the course of sepsis increases mortality twice, while chronic kidney
      disease develops in 50% of the patients who survived sepsis. The pathophysiology
      of acute kidney injury (AKI) development in the course of sepsis is not fully
      understood. Some researchers, to emphasize the distinctiveness of AKI in the
      course of sepsis, describe the changes that occur in the kidneys in its course as
      sepsis induced-AKI. In the last decade, the theory regarding the possibility of
      modulation of inflammatory pathways through extracorporeal blood purification
      methods (HCO - using high cut off membranes) from pro-inflammatory cytokines and
      attempts to restore homeostasis in this way has gained great recognition. The
      basis for the implementation of this type of treatment was the "maximum
      concentration" hypothesis, which assumes that, avoiding the onset of the early
      peak of circulating proinflammatory molecules is possible to prevent and modulate
      the clinical effects of an excessively expressed inflammatory reaction in the
      course of sepsis. This study is an attempt to analyze and summarize the current
      state of knowledge on the effectiveness of using HCO membranes in patients with
      sepsis who have developed AKI. For this purpose, the resources of MEDLAIN/Pubmed
      bases from 1965 to April 2018 have been analyzed, taking into account only the
      full versions of articles in English, using a combination of the following words:
      super high-flux, high cut-off, dialysis, renal replacement therapy, filtration,
      diafiltration, hemodialysis, hemofiltration, hemodiafiltration, sepsis, cytokine,
      inflammatory mediators, inflammation.

PMID- 30240378
TI  - [Selected indicators of inflammation in patients hospitalized with various
      degrees of obesity and metabolic syndrome].
AB  - : In people with metabolic syndrome, obesity and diseases of the cardiovascular
      system are more often observed. At the basis of the pathogenesis of the metabolic
      syndrome, chronic inflammation plays a significant role. One of the markers of
      this process is C-reactive protein (CRP) - one of the indicators of the acute
      phase of inflammation. The role of other biochemical parameters in obesity has
      been less well understood. AIM: The aim of the study is to assess the correlation
      of selected factors of inflammation in obese people and the relevant
      anthropometric parameters. MATERIALS AND METHODS: 263 patients participated in
      the study. In all subjects anthropometric measurements (body weight, waist/hip
      ratio and body mass index) were performed and selected biochemical parameters
      related to MS were determined. The obtained data were analyzed with the division
      into three degrees of obesity, taking into account gender and place of residence.
      RESULTS: The mean C-reactive protein (CRP) concentration was 5,32 +/- 14 mg/dl;
      in women, the highest concentration in 2 degrees  of obesity (5mg/dL) and in men
      in 1-potency (8,41mg/dL). A statistically significant difference in the level of
      leukocytes between 1 degrees  and 3 degrees  of obesity in the study group was
      obtained (p = 0,02). In 3 degrees  of obesity in both sexes the highest
      concentration of monocytes was demonstrated. Positive correlations between
      leukocyte levels and individual parameters were demonstrated: triglyceride levels
      (r = 0,134); and the BMI value (r = 0,155); a waist (r = 0,147); and the level of
      PLT (r = 0,381) and RBC (r = 0,187). CONCLUSIONS: The consequence of obesity is
      the continuous production of inflammatory factors causing destruction of the
      body's own tissues. In the present study, CRP values were shown to slightly
      exceed (p<0,05) above the accepted norm, while the remaining analyzed indicators
      were within diagnostic standards (in their upper ranges).

PMID- 30240379
TI  - [Anxiety and depressive symptoms in epilepsy in the context of defense mechanisms
      and electrodermal activity].
AB  - : Depressive and anxiety disorders among people with epilepsy are more common
      than in general population and they are associated with less efficient emotion
      regulation and reduced quality of life. Unfortunately, these disorders are not
      always correctly diagnosed or treated. Some studies suggest that the
      electrodermal activity may serve as a marker for depression. AIM: The aim of the
      study was to measure and compare depressive and anxiety symptoms, defense
      mechanisms and electrodermal activity in response to cognitive stimulation in
      patients with epilepsy with the control group, and to test the correlations
      between symptoms of anxiety and depression, defense mechanisms and the
      electrodermal activity. MATERIALS AND METHODS: 64 patients diagnosed with
      epilepsy and 66 people from the control group were assessed with following
      psychological questionnaires: State-Trait Anxiety Inventory, Beck Depression
      Inventory, Defense Styles Questionnaire 40. MindLAB Set was used to measure
      electrodermal activity. RESULTS: The study showed that people with epilepsy tend
      to have increased levels of anxiety and depressive symptoms compared with the
      control group. Patients also tend to use neurotic defense mechanisms what may be
      associated with poorer emotion regulation. Electrodermal activity was lower among
      people with epilepsy after cognitive stimulation. There was no statistically
      significant correlation between electrodermal activity, anxiety and depressive
      symptoms. CONCLUSIONS: The results indicate the need for assessment of anxiety,
      depressive symptoms and types of defense mechanisms among patients with epilepsy,
      as appropriate psychotherapeutic and/or pharmacological intervention could
      significantly improve the quality of life of these patients.

PMID- 30240380
TI  - [Pulmonary embolism in a girl with nephrotic syndrome and factor V Leiden - case
      report].
AB  - : Thromboembolic complications are found in 2-3% of children with nephrotic
      syndrome (NS); this increased risk is caused by hypovolemia, hemoconcentration,
      increased number and activity of platelets, hyperfibrinogenemia and loss of
      coagulation inhibitors. Risk is even higher in case of additional factors e.g.
      congenital thrombophilia. CASE REPORT: Girl with NS aged 17 11/12 years was
      admitted to hospital due to respiratory tract infection with cough and back pain.
      NS started 9 months earlier and she had two bouts of disease, and was treated
      only with prednisone (current dose - 60 mg/48h). On admission she was without any
      abnormalities on auscultation, with BP 111/65 mmHg, HR 80 bpm, satO2 99%. Lab
      results showed the increase of WBC 18.3*103/MUL, D-dimers 23038 MUg/L and
      proteinuria 900 mg/dL. Other values of examined parameters were in normal limits.
      Chest X-ray and ECG were also normal. Presumptive diagnosis of pulmonary embolism
      was made and the patient was given 1000IU of antithrombin III and nadroparine
      (2x90IU/kg/24h s.c.). In ECHO the occlusion of left pulmonary artery and
      preserved blood flow in right were revealed. In angioCT clot nearly filling lumen
      of left pulmonary artery, clot in intermediate part of right pulmonary artery,
      and focus of pulmonary infarction in 10th segment of left lung were found.
      Doppler USG of lower limb veins did not reveal thrombi or perforator vein
      incompetence. Treatment with nadroparine was continued, and rapid improvement of
      clinical condition and disappearance of pain and cough were observed.
      Mycophenolate mofetil was added, which resulted in subsidence of proteinuria.
      Rivaroxaban was used in prophylaxis of recurrences of thromboembolism. Tests for
      thrombophilia revealed factor V Leiden in patient.

PMID- 30240381
TI  - Atypical hemolytic uremic syndrome: a new drug program and first Polish adult
      patient treated with eculizumab.
AB  - Atypical hemolytic uremic syndrome (aHUS) is an extremely rare disease
      characterized by acute kidney injury, thrombocytopenia, and microangiopathic
      hemolytic anemia. Majority of patients have an underlying complement abnormality
      what makes aHUS possible to treat using eculizumab, antibody against the
      complement protein C5. Up to 2018, Polish adult patients were treated using
      glucocorticosteroids, plasma exchange or plasma infusion. Unfortunately, such
      protocols/ interventions were associated with poor prognosis; about 67% of adult
      patients with aHUS had been progressing to end-stage renal disease or had died
      within three years after diagnosis. Release of eculizumab significantly improve
      the prognosis of aHUS. We describe new drug program and case of first included
      adult patient: after ineffective nonspecific treatment of aHUS with plasma
      infusions (10 units), plasma exchanges (7 sessions) and glucocorticosteroids, we
      decided to introduce eculizumab. The clinical and laboratory tests showed
      effectiveness of the therapy after sixth infusion; no adverse effects were
      observed.

PMID- 30240382
TI  - [The role of electrical bioimpedance in the evaluation of the hydration status of
      patients with liver cirrhosis].
AB  - Patients with liver cirrhosis are a group particularly exposed to the development
      of water and electrolyte disturbances, having a significant impact on the course
      of the disease and the quality of life. Precise and rapid assessment of the
      hydration status of patients often determines the further course of the disease,
      the success of treatment and the time of hospitalization. For this reason, it is
      important to maintain the water and electrolyte balance in a state of
      equilibrium. So far, no one optimized diagnostic tool has been found to assess
      the hydration status of the organism, which would become a gold standard. Despite
      some limitations, it should be noted that the electrical bioimpedance (BIA)
      method makes it possible to assess the total body water volume, extracellular
      space, intracellular space, as well as the content of sodium ions, which affects
      the flow of fluids between these spaces. It is an excellent non-invasive tool in
      diagnosing hydration status of patients with liver cirrhosis, kidney failure and
      cardiovascular diseases.

PMID- 30240383
TI  - [Stimulation of spermatogenesis in men with hypogonadotropic hypogonadism].
AB  - Hypogonadotropic hypogonadism (HH) is characterizes by infertility. In patients
      with congenital HH (CHH) is caused by the deficient production, secretion or
      action of gonadotropin-releasing hormone (GnRH), and clinically is characterized
      by an absence of puberty and infertility. In patients with acquired HH (AHH)
      impaired fertility is the main symptom. An important diagnostic challenge is to
      distinguish CHH from constitutional delay of growth and puberty (CDGP). In
      patients with CHH after stimulation of puberty and in patients with AHH after
      diagnosis, hormonal stimulation of spermatogenesis is necessary. For most men
      with low sperm concentrations due to HH, GnRH or gonadotropin therapy effectively
      increases spermatogenesis. Such treatment may help the patient obtain offspring
      using the natural method or with the use of assisted reproduction techniques
      (ART). Gonadotropin therapy is not recommended for men with idiopathic
      infertility and normal LH, and FSH levels.

PMID- 30240384
TI  - [The emotional intelligence in major depressive disorders].
AB  - The term emotional intelligence was introduced by Salovey & Mayer. It is the
      individual's ability to perceive, evaluate and express emotions. It is also a set
      of abilities which enable an individual to function effectively and they are an
      important factor affecting the quality of life. The literature also has a
      synonymous concept of emotional competence which is a collection of already
      acquired skills used in specific social situations. Major depressive disorder
      represents an affective disorder having an impact on a human being's ability to
      regulate emotions. In their course, there are difficulties with adequate
      recognition of one's emotional states as well as emotional states of other
      people. Research indicates, among others, the relationship between emotional
      intelligence and the occurrence of suicidal thoughts and tendencies, prognosis of
      therapeutic interactions in patients. A high level of emotional intelligence is a
      protective factor in the occurrence of mental disorders, including depression,
      affects the treatment process and influences the creation of effective strategies
      for coping with stress. The paper presents reports on the level of emotional
      intelligence and its impact on the functioning of patients with major depressive
      disorders.

PMID- 30240385
TI  - [The importance of the ketamine in depressive disorders].
AB  - Depressive disorders are the most common disease entities in psychiatry. Slightly
      more than 50% of patients diagnosed with major depressive disorder (MDD) were
      treated using available antidepressants have shown the complete remission, and
      over 1/3 of patients have not responded to conventional treatment presenting
      treatment-resistant depression (TRD). Possible treatment of this type of disorder
      is pharmacotherapy, which in some cases turns out to be ineffective. Scientists
      studying this problem suggest using ketamine - a drug known for being used in
      anaesthesiology and intensive therapy.

PMID- 30240386
TI  - Mitochondrial Dynamics in Rat Heart Induced by 5-Fluorouracil.
AB  - BACKGROUND Patients treated with 5-FU can develop rare but potentially severe
      cardiac effects, including cardiomyopathy, angina pectoris, ventricular
      tachycardia, heart failure, acute myocardial infarction, and cardiogenic shock.
      The specific pathologies and mechanisms are not fully understood. Research found
      that mitochondrial dynamics are widely detected in many angiocardiopathies.
      Therefore, in the present study we studied the mitochondrial damage and explored
      the role of mitochondrial fusion/fission proteins on myocardium of rats treated
      with 5-fluorouracil (5-FU). MATERIAL AND METHODS Thirty male SD rats were
      randomly divided into 3 groups with 10 rats in each group: (1) control group, (2)
      low 5-FU group (25 mg/kg), (3) high 5-FU group (50 mg/kg). The animals received
      intraperitoneal injection for 5 consecutive days. We assessed alterations in
      mitochondrial morphology, ATP content, mitochondrial membrane potential, and
      mitochondria fusion/fission proteins expression in hearts of rats receiving
      intraperitoneal injection with different doses of 5-FU. RESULTS 5-FU
      intraperitoneal injection induced ultra-structural damage in hearts, such as
      mitochondrial swelling, cristae disorder, and vacuolization. These changes were
      accompanied by decreases of mitochondrial membrane potential. The low dose of 5
      FU led to a slight increase in ATP content. However, the high 5-FU dose caused a
      more significant reduction compared with the control group. Furthermore, 5-FU
      intraperitoneal injection significantly increased specific mitochondrial fission
      proteins (Drp1 and Fis1) and decreased mitochondrial fusion proteins (Opa1, Mfn1,
      and Mfn2) in rat hearts. However, no changes in cardiac structure and function
      were detected by echocardiogram. The high dose caused more damage to
      mitochondrial function than the low dose. CONCLUSIONS Mitochondrial damage is a
      potentially important mechanism and early indicator for 5-FU-induced
      cardiovascular disease.

PMID- 30240387
TI  - Is treatment with stem cells effective in Parkinson's disease?
AB  - INTRODUCTION: There are many patients with Parkinson's disease who have a limited
      response to conventional pharmacological treatment. The use of stem cells has
      been postulated as an alternative, although its effectiveness remains a matter of
      controversy. 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 two systematic
      reviews including 21 studies overall, of which three were randomized trials. We
      concluded it is not clear whether stem cells have any effect on the symptoms of
      Parkinson's disease because the certainty of the available evidence is very low.

PMID- 30240388
TI  - Is Ahmed valve superior to Baerveldt implant as an aqueous shunt for the
      treatment of glaucoma?
AB  - INTRODUCTION: Aqueous shunt has emerged as an alternative technique to
      trabeculectomy, considered the standard for glaucoma surgery. Currently, it is
      mainly indicated after failure of trabeculectomy or in glaucoma with high risk of
      failure. The Ahmed valve and the Baerveldt implant are the most commonly used
      aqueous shunts. However, it is not clear whether there are differences between
      them. 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 five systematic
      reviews including 10 studies overall, of which two were randomized trials. We
      concluded the Ahmed valve probably achieves a lower decrease in intraocular
      pressure, might lead to less qualified success and probably needs more
      reinterventions than the Baerveldt implant. Regarding safety profile, the Ahmed
      valve is not clearly superior or inferior to the Baerveldt implant.

PMID- 30240389
TI  - Atypical presentation and late diagnosis of acute aortic dissection without
      timely surgical treatment: case report and literature review.
AB  - Acute aortic syndrome includes a group of diseases that have clinical similarity
      in their natural history, the most important characteristic being their
      association with a high vital risk. The diagnosis and management of aortic
      dissection depends on the degree of aortic involvement according to the location
      of the lesion, as defined by the Stanford classification. In this syndrome, chest
      pain is considered the cardinal symptom; however, there are situations where
      clinical feedback is difficult. We present the case of a patient who debuted with
      a Stanford A aortic dissection, with an indication for surgical resolution in the
      acute phase, but who unexpectedly presented unspecific clinical manifestations.
      An opportune diagnosis was not obtained. After repeated consultations for changes
      in his symptoms, the definitive diagnosis was determined through imaging study,
      evolving favorably with ambulatory therapy.

PMID- 30240390
TI  - Three-dimensional culture of chicken primordial germ cells (cPGCs) in defined
      media containing the functional polymer FP003.
AB  - Scalable production of avian cell lines exhibits a valuable potential on
      therapeutic application by producing recombinant proteins and as the substrate
      for virus growth due to the special glycosylation occurs in avian species.
      Chicken primordial germ cells (cPGCs), a germinal pluripotent avian cell type,
      present the ability of self-renewal, an anchorage-independent cell growth and the
      ability to be genetically modified. This cell type could be an interesting
      bioreactor system for industrial purposes. This study sought to establish an
      expandable culture system with defined components for three-dimensional (3D)
      culture of cPGCs. cPGCs were cultured in medium supplemented with the functional
      polymer FP003. Viscoelasticity was low in this medium but cPGCs did not sediment
      in culture and efficiencies of space and nutrient utilization were thus enhanced
      and consequently their expansion was improved. The total number of cPGCs
      increased by 17-fold after 1 week of culture in 3D-FAot medium, an aseric defined
      medium containing FP003 polymer, FGF2 and Activin A as growth factors and
      Ovotransferrin as protein. Moreover, cPGC cell lines stably expressed the
      germline-specific reporter VASA:tdTOMATO, as well as other markers of cPGCs, for
      more than 1 month upon culture in 3D-FAot medium, indicating that the
      characteristics of these cells are maintained. In summary, this novel 3D culture
      system can be used to efficiently expand cPGCs in suspension without mechanical
      stirring, which is available for long-term culture and no loss of cellular
      properties was found. This system provides a platform for large-scale culture of
      cPGCs.

PMID- 30240392
TI  - The number of undocumented immigrants in the United States: Estimates based on
      demographic modeling with data from 1990 to 2016.
AB  - We apply standard demographic principles of inflows and outflows to estimate the
      number of undocumented immigrants in the United States, using the best available
      data, including some that have only recently become available. Our analysis
      covers the years 1990 to 2016. We develop an estimate of the number of
      undocumented immigrants based on parameter values that tend to underestimate
      undocumented immigrant inflows and overstate outflows; we also show the
      probability distribution for the number of undocumented immigrants based on
      simulating our model over parameter value ranges. Our conservative estimate is
      16.7 million for 2016, nearly fifty percent higher than the most prominent
      current estimate of 11.3 million, which is based on survey data and thus
      different sources and methods. The mean estimate based on our simulation analysis
      is 22.1 million, essentially double the current widely accepted estimate. Our
      model predicts a similar trajectory of growth in the number of undocumented
      immigrants over the years of our analysis, but at a higher level. While our
      analysis delivers different results, we note that it is based on many
      assumptions. The most critical of these concern border apprehension rates and
      voluntary emigration rates of undocumented immigrants in the U.S. These rates are
      uncertain, especially in the 1990's and early 2000's, which is when-both based on
      our modeling and the very different survey data approach-the number of
      undocumented immigrants increases most significantly. Our results, while based on
      a number of assumptions and uncertainties, could help frame debates about
      policies whose consequences depend on the number of undocumented immigrants in
      the United States.

PMID- 30240391
TI  - An integration of phenotypic and transcriptomic data analysis reveals yield
      related hub genes in Jatropha curcas inflorescence.
AB  - Jatropha curcas is an oil-rich seed crop with huge potentials for bioenergy
      production. The inflorescence carries a number of processes that are likely to
      affect the overall yield potentials; floral development, male-to-female flower
      ratio, floral abscission and fruit set. In this study, a weighted gene co
      expression network analysis which integrates the transcriptome, physical and
      simple sugar data of J. curcas inflorescence was performed and nine modules were
      identified by means of hierarchical clustering. Among them, four modules (green4,
      antiquewhite2, brown2 and lightskyblue4) showed significant correlation to yield
      factors at p<=0.01. The four modules are categorized into two clusters; cluster 1
      of green4 and antiquewhite2 modules correspond to number of
      flowers/inflorescence, total seed weight/plant, number of seeds/plant, and number
      of fruits/plant, whereas cluster 2 of brown2 and lightskyblue4 modules correspond
      to glucose and fructose. Descriptive characterizations of cluster 1 show putative
      involvement in gibberellin signaling and responses, whereas cluster 2 may have
      been involved in sugar signaling, signal transductions and regulation of
      flowerings. Our findings present a list of hub genes for J. curcas yield
      improvement and reproductive biology enhancement strategies.

PMID- 30240394
TI  - Minimizing marine ingredients in diets of farmed Atlantic salmon (Salmo salar):
      Effects on growth performance and muscle lipid and fatty acid composition.
AB  - Due to limited fish meal and fish oil resources and their high costs for the
      aquaculture industry, it is necessary to find alternative sustainable sources of
      protein and lipids. Therefore, seven different diets were formulated with
      different levels of animal by-products, vegetable proteins, fish oil and rapeseed
      oil, to feed farmed Atlantic salmon, and their effects on growth performance,
      muscle lipid class, and fatty acid composition were examined. Protein sources
      included anchovy, poultry, feather, blood, corn, soy and wheat. Growth
      performance indicated that the diet with the lowest fish meal and fish oil
      content resulted in the lowest weight gain and final weight, followed by the diet
      containing the highest level of animal by-products. The lipid class analysis
      showed no statistical difference in the muscle total lipid content using
      different diets. However, significant statistical differences were observed among
      the main lipid classes; triacylglycerols, phospholipids, and sterols. The diet
      containing 1.4% omega-3 long-chain fatty acids resulted in the highest content of
      triacylglycerols and phospholipids. Diets containing medium and low levels of
      fish oil and fish meal, respectively, led to as high a level of omega3 fatty
      acids in muscle as when fish were fed diets with high levels of fish meal and
      fish oil. The results of this study suggest that feeding a diet containing low
      levels of fish meal and moderate levels of fish oil does not significantly affect
      omega3 fatty acid composition in muscle. Fish meal could be reduced to 5% without
      affecting growth as long as there was a minimum of 5% fish oil, and animal by
      products did not exceed 26% of the diet.

PMID- 30240393
TI  - A voluntary conservation agreement reduces the risks of lethal collisions between
      ships and whales in the St. Lawrence Estuary (Quebec, Canada): From co
      construction to monitoring compliance and assessing effectiveness.
AB  - Lethal collisions with ships are limiting the recovery of several at-risk whale
      species worldwide. In the St. Lawrence Estuary (Quebec, Canada), the endangered
      blue whale and of special concern fin whale are among the migratory species
      subject to collisions with large ships. In 2011, a working group composed of
      representatives from the maritime industry, the government, non-governmental
      organizations, and academia was created to explore solutions to mitigate ship
      whale collisions in the St. Lawrence Estuary. Adopting an adaptive risk
      management framework, the working group took advantage of the best available
      scientific data and tools to co-construct realistic collision mitigation options
      and evaluate their likely benefits for whale conservation and costs for the
      industry. In 2013, the working group recommended the implementation of voluntary
      measures to mitigate collision risks, consisting of a slow-down area, a no-go
      area, and a caution area; a recommended route was added in 2014. Along with the
      voluntary framework, the working group agreed to continuously monitor compliance
      with and assess effectiveness of these mitigation measures. After the fourth year
      of implementation, voluntary measures showed encouraging results, with a
      reduction of up to 40% of lethal collision risks with fin whales in the highest
      density area. This reduction in risk is mainly related to ship speed reduction in
      the slow-down area from 14.1 +/- 2.6 knots in 2012 to 11.3 +/- 1.7 knots since
      2014. The presence of a mandatory pilotage area overlapping with the slow-down
      area was instrumental to facilitate communication about the mitigation measures,
      with the pilotage corporation sitting as a regular member of the working group.
      This resulted in significantly slower speeds in the slow-down area for ships with
      a pilot from the pilotage corporation onboard compared to those without (-0.8
      knots, p-value < 0.001). It is also likely to explain the weaker compliance of
      the maritime industry with the no-go area located outside of the mandatory
      pilotage area. Other factors of success include: the continuous dedication of the
      government to a voluntary and transparent participatory process; the use of
      available data, tools and institutions; the presence of an environmental
      certification program representative in the working group; and the adoption by
      consensus of an adaptive risk management approach. The traditional regulatory
      approach to conservation is often blamed for its focus on deterring negative
      behaviors, doing nothing to encourage and reward positive ones. In agreement with
      other case studies, the benefits of the voluntary measures implemented in the St.
      Lawrence Estuary include the pro-active commitment from the industry (which is
      likely to reduce conflicts with regulators), the greater flexibility and freedom
      that allowed to come up with cost-effective and tailored-made mitigation
      measures, and the fast achievement of conservation gains. More importantly
      perhaps, the human and working capital built throughout the concertation process
      have the potential to be a fundamental cornerstone in dealing with more complex
      issues such as the chronically increasing level of underwater noise in whale
      habitats.

PMID- 30240395
TI  - Anti-parasitic effect of vitamin C alone and in combination with benznidazole
      against Trypanosoma cruzi.
AB  - BACKGROUND: Drugs currently used for the treatment of Chagas' disease, nifurtimox
      and benznidazole, have a limited effectiveness and toxic side effects. With the
      aim of finding new therapeutic approaches, in vitro and in vivo anti-Trypanosoma
      cruzi activity of vitamin C alone and combined with benznidazole were
      investigated. METHODOLOGY/PRINCIPAL FINDINGS: The trypanocidal activity on
      epimastigote and trypomastigote forms was evaluated by counting parasites in a
      Neubauer chamber after treatment with the compounds. For the amastigote stage,
      transgenic parasites expressing beta-galactosidase were used and quantified by
      measuring the beta-galactosidase activity. The cytotoxicity of compounds was
      tested on Vero cells. The redox state of the parasite was evaluated by
      determining the reduced thiol levels (spectrophotometric assay) and the
      intracellular oxidative state (by flow cytometry). The in vivo trypanocidal
      activity was evaluated on a murine model of Chagas' disease. The trypanocidal
      activity of vitamin C and benznidazole was similar for the three parasite forms.
      When combining both drugs, vitamin C did not induce any change in the
      antiparasitic activity of benznidazole on trypomastigotes; however, on mammal
      cells, vitamin C diminished the cytotoxicity degree of benznidazole. Two
      mechanisms of action may be postulated for vitamin C: a lethal pro-oxidant effect
      on the parasite when used alone, and an antioxidant effect, when combined with
      benznidazole. A similar behavior was observed on infected mice; i.e., parasite
      counts in infected mice treated with vitamin C were lower than that of the
      control group. Animals treated with benznidazole presented lower parasitemia
      levels, as compared with those treated with vitamin C alone. Again, vitamin C did
      not cause any effect on the antiparasitic profile of benznidazole. Even though a
      combined treatment was employed, the antioxidant effect of vitamin C on the host
      was evidenced; a 100% survival was observed and the weight loss occurring during
      the acute phase of the infection was reduced. CONCLUSIONS/SIGNIFICANCE: Based on
      these results, the combination of vitamin C with benznidazole could be considered
      as an alternative treatment for Chagas' disease. These preliminary results
      encourage further research to improve the treatment of Chagas' disease.

PMID- 30240396
TI  - Changes of body composition after valve surgery in patients with mitral valve
      disease.
AB  - BACKGROUND: Patients with chronic heart failure have alteration in body
      composition as a reduction in fat mass, lean body mass and bone mass. However,
      body wasting in valvular heart disease and the impact of corrective valvular
      surgery on body composition has not been investigated. OBJECTIVES: We
      hypothesized that body wasting in severe mitral valve (MV) diseases is reversible
      through MV surgery. METHODS: Forty eight patients who were scheduled to undergo
      MV surgery were consecutively enrolled after excluding patients with combined
      valvular heart disease, ischemic heart disease, cardiomyopathies, and diseases or
      who were taking medications that could affect metabolism. All patients were
      subjected to simplified nutritional assessment questionnaire (SNAQ) for appetite,
      laboratory tests, echocardiography, and dual-energy X-ray absorptiometry (DXA)
      before and one year after MV surgery. RESULTS: One year after MV surgery, the
      patients showed increased appetite and improved laboratory data as well as
      hemodynamic improvement.When we classified the patients according to the primary
      MV lesion, no changes in body weight were observed in both patients with mitral
      regurgitation (MR) and mitral stenosis (MS). However, significant increase in
      bone mineral density and body fat percentage were observed in patients with MR
      and not in patients with MS. In patients with MR, patients with Deltafat >= 2%
      showed significantly higher pre-operative estimated right ventricular systolic
      pressure (eRVSP) level and greater decrease in eRVSP after surgery than those
      with Deltafat < 2% and both DeltaSNAQ and Deltafat showed significant negative
      relationship with DeltaeRVSP, respectively. CONCLUSIONS: In patients with severe
      MV disease, corrective MV surgery led to favorable outcomes in wasting process as
      well as hemodynamic improvement. Particularly, right ventricular pressure
      overload showed a close association with the changes in appetite and body fat
      percentage in patients with MR.

PMID- 30240397
TI  - Effects of variability in daily light integrals on the photophysiology of the
      corals Pachyseris speciosa and Acropora millepora.
AB  - Phototrophic sessile organisms, such as reef corals, adjust their photosynthetic
      apparatus to optimize the balance of light capture versus protection in response
      to variable light availability (photoacclimation). In shallow marine
      environments, daily light integrals (DLI) can vary several-fold in response to
      water clarity and clouds. This laboratory study investigated the responses of two
      coral species to fluctuations in DLI. Corals were exposed to four contrasting DLI
      treatments: 'high-light' (potentially photoinhibiting conditions, 32 mol photons
      m-2 d-1), 'low-light' (potentially light-limiting conditions, 6 mol photons m-2 d
      1), and two 'variable light' treatments that alternated between high and low
      conditions every 5 days. In the variable treatments, the shade-tolerant coral
      Pachyseris speciosa displayed cycles of rapid declines in maximum quantum yield
      during high-light and subsequent recoveries during low-light, showing
      photoacclimation at a time scale of 3-5 days. In contrast, the shallow-water
      coral Acropora millepora showed slow (>20 days) photoacclimation, and minimal
      changes in photosynthetic yields despite contrasting light exposure. However,
      growth (change in buoyant weight) in A. millepora was significantly slower under
      variable light, and even more so under low-light conditions, compared with high
      light conditions. The responses of yields in P. speciosa match their preference
      for low-light environments, but suggest a vulnerability to even short periods of
      high-light exposure. In contrast, A. millepora had better tolerance of high-light
      conditions, however its slow photoacclimatory responses limit its growth under
      low and variable conditions. The study shows contrasting photoacclimatory
      responses in variable light environments, which is important to identify and
      understand as many coastal and midshelf reefs are becoming increasingly more
      turbid, and may experience higher variability in light availability.

PMID- 30240398
TI  - Survival prediction among patients with non-cancer-related end-stage liver
      disease.
AB  - BACKGROUND: Predicting the survival of non-cancer related end-stage-liver-disease
      patients in general practice has been difficult for physicians because of the
      extremely variable trajectories due to multiple complex clinical factors, hence
      it remains a challenging issue to date. This study aimed to develop and validate
      a specific prognostic scoring system to early recognize the prognosis and improve
      the quality of end-of life care for non-cancer end-stage-liver-disease
      population. MATERIALS AND METHODS: A multicentre, retrospective cohort study was
      conducted during January 2010 ~ December 2012 and continued follow-up until
      December 2014. A cox proportional hazard regression analysis was used to derive
      and validate an optimized model. The main outcome measures were the 28-day, 3
      month, 6-month, and 12-month mortality prediction. The performance of the novel
      model was evaluated, including discrimination and calibration. RESULTS: A total
      of 4,080 consecutive subjects were enrolled. The AUROCs for the 3-month survival
      discrimination in the MELD, MELD-Na and novel model were 0.787, 0.705 and 0.804
      (P<0.001); the 6-month survival discrimination were 0.781, 0.702 and 0.797
      (P<0.001); the overall survival discrimination were 0.771, 0.694 and 0.785 (P =
      0.002) respectively, whereas the novel model showed a significantly higher
      discrimination power than did the MELD and MELD-Na for the 3-month, 6-month and
      overall survival prediction. In addition, calibration of external validation
      cohort showed no statistical difference in all 5 groups compared with the
      observed groups. CONCLUSION: This is a clinically relevant, validated scoring
      system that can be used sequentially to stratify the prognosis in non-cancer
      cirrhotic populations, which may help the patients along with medical team in
      decision making to improve the quality of end-of-life care.

PMID- 30240399
TI  - Projected impacts of future climate change, ocean acidification, and management
      on the US Atlantic sea scallop (Placopecten magellanicus) fishery.
AB  - Ocean acidification has the potential to significantly impact both aquaculture
      and wild-caught mollusk fisheries around the world. In this work, we build upon a
      previously published integrated assessment model of the US Atlantic Sea Scallop
      (Placopecten magellanicus) fishery to determine the possible future of the
      fishery under a suite of climate, economic, biological, and management scenarios.
      We developed a 4x4x4x4 hypercube scenario framework that resulted in 256 possible
      combinations of future scenarios. The study highlights the potential impacts of
      ocean acidification and management for a subset of future climate scenarios, with
      a high CO2 emissions case (RCP8.5) and lower CO2 emissions and climate mitigation
      case (RCP4.5). Under RCP4.5 and the highest impact and management scenario, ocean
      acidification has the potential to reduce sea scallop biomass by approximately
      13% by the end of century; however, the lesser impact scenarios cause very little
      change. Under RCP8.5, sea scallop biomass may decline by more than 50% by the end
      of century, leading to subsequent declines in industry landings and revenue.
      Management-set catch limits improve the outcomes of the fishery under both
      climate scenarios, and the addition of a 10% area closure increases future
      biomass by more than 25% under the highest ocean acidification impacts. However,
      increased management still does not stop the projected long-term decline of the
      fishery under ocean acidification scenarios. Given our incomplete understanding
      of acidification impacts on P. magellanicus, these declines, along with the high
      value of the industry, suggest population-level effects of acidification should
      be a clear research priority. Projections described in this manuscript illustrate
      both the potential impacts of ocean acidification under a business-as-usual and a
      moderately strong climate-policy scenario. We also illustrate the importance of
      fisheries management targets in improving the long-term outcome of the P.
      magellanicus fishery under potential global change.

PMID- 30240400
TI  - Factors that affect immunization data quality in Kabarole District, Uganda.
AB  - INTRODUCTION: Reliable and timely immunization data is vital at all levels of
      health care to inform decisions and improve program performance. Inadequate data
      quality may impair our understanding of the true vaccination coverage and also
      hinder our capability to meet the program objectives. It's therefore important to
      regularly assess immunization data quality to ensure good performance, sound
      decision making and efficient use of resources. METHODS: We conducted an
      immunization data quality audit between July and August 2016. The verification
      factor was estimated by dividing the recounted diphtheria, pertussis and tetanus
      third dose vaccination for children under 1 year (DPT3<1 year) by reported DPT3<1
      year. The quality of data collection processes was measured using quality indices
      for the 3 different components: recording practices, storage/reporting,
      monitoring and evaluation. These indices were applied to the different levels of
      the health care service delivery system. Quality index score was estimated by
      dividing the total question or observation correctly answered by the total number
      of answers/ observations for a particular component. RESULTS: The mean health
      center verification factor was 87%. Sixty five percent (32/49) of the health
      centers had consistent data, 27% (13/49) over reported and 4% (2/49) under
      reported. Health center 11s and 111s contributed to over-reporting and under
      reporting. All the health centers' reports were complete and timely between
      January and June and from November to December. The mean quality indices for the
      3 different componets assessed were; recording practices 66%, storing/reporting
      75%, monitoring and evaluation 43%. There was a weak positive correlation between
      the health center verifaction factor and quality index though this was not
      statistically significant (r = 0.014; p = 0.92). CONCLUSION: Lower level health
      centers contributed significantly to the inconsistencies in immunization data;
      there were wide variation between the quality indices of recording practices,
      storage/reporting, monitoring and evaluation. We recommended that District Local
      Governments and Ministry of Health focus on improving data quality at lower
      levels of health service delivery.

PMID- 30240402
TI  - Spatial transmission of H5N2 highly pathogenic avian influenza between Minnesota
      poultry premises during the 2015 outbreak.
AB  - The spatial spread of highly pathogenic avian influenza (HPAI) H5N2 during the
      2015 outbreak in the U.S. state of Minnesota was analyzed through the estimation
      of a spatial transmission kernel, which quantifies the infection hazard an
      infectious premises poses to an uninfected premises some given distance away.
      Parameters were estimated using a maximum likelihood method for the entire
      outbreak as well as for two phases defined by the daily number of newly detected
      HPAI-positive premises. The results indicate both a strong dependence of the
      likelihood of transmission on distance and a significant distance-independent
      component of outbreak spread for the overall outbreak. The results further
      suggest that HPAI spread differed during the later phase of the outbreak. The
      estimated spatial transmission kernel was used to compare the Minnesota outbreak
      with previous HPAI outbreaks in the Netherlands and Italy to contextualize the
      Minnesota transmission kernel results and make additional inferences about HPAI
      transmission during the Minnesota outbreak. Lastly, the spatial transmission
      kernel was used to identify high risk areas for HPAI spread in Minnesota. Risk
      maps were also used to evaluate the potential impact of an early marketing
      strategy implemented by poultry producers in a county in Minnesota during the
      outbreak, with results providing evidence that the strategy was successful in
      reducing the potential for HPAI spread.

PMID- 30240403
TI  - An enriched environment prevents diabetes-induced cognitive impairment in rats by
      enhancing exosomal miR-146a secretion from endogenous bone marrow-derived
      mesenchymal stem cells.
AB  - Increasing evidence suggests that an enriched environment (EE) ameliorates
      cognitive impairment by promoting repair of brain damage. However, the mechanisms
      by which this occurs have not been determined. To address this issue, we
      investigated whether an EE enhanced the capability of endogenous bone marrow
      derived mesenchymal stem/stromal cells (BM-MSCs) to prevent hippocampal damage
      due to diabetes by focusing on miRNA carried in BM-MSC-derived exosomes. In
      diabetic streptozotocin (STZ) rats housed in an EE (STZ/EE), cognitive impairment
      was significantly reduced, and both neuronal and astroglial damage in the
      hippocampus was alleviated compared with STZ rats housed in conventional cages
      (STZ/CC). BM-MSCs isolated from STZ/CC rats had functional and morphological
      abnormalities that were not detected in STZ/EE BM-MSCs. The miR-146a levels in
      exosomes in conditioned medium of cultured BM-MSCs and serum from STZ/CC rats
      were decreased compared with non-diabetic rats, and the level was restored in
      STZ/EE rats. Thus, the data suggest that increased levels of miR-146a in sera
      were derived from endogenous BM-MSCs in STZ/EE rats. To examine the possibility
      that increased miR-146a in serum may exert anti-inflammatory effects on
      astrocytes in diabetic rats, astrocytes transfected with miR-146a were stimulated
      with advanced glycation end products (AGEs) to mimic diabetic conditions. The
      expression of IRAK1, NF-kappaB, and tumor necrosis factor-alpha was significantly
      higher in AGE-stimulated astrocytes, and these factors were decreased in miR-146a
      transfected astrocytes. These results suggested that EEs stimulate up-regulation
      of exosomal miR-146a secretion by endogenous BM-MSCs, which exerts anti
      inflammatory effects on damaged astrocytes and prevents diabetes-induced
      cognitive impairment.

PMID- 30240401
TI  - Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U
      BIOPRED cohort.
AB  - Oxidative stress is believed to be a major driver of inflammation in smoking
      asthmatics. The U-BIOPRED project recruited a cohort of Severe Asthma smokers/ex
      smokers (SAs/ex) and non-smokers (SAn) with extensive clinical and biomarker
      information enabling characterization of these subjects. We investigated
      oxidative stress in severe asthma subjects by analysing urinary 8-iso-PGF2alpha
      and the mRNA-expression of the main pro-oxidant (NOX2; NOSs) and anti-oxidant
      (SODs; CAT; GPX1) enzymes in the airways of SAs/ex and SAn. All the severe asthma
      U-BIOPRED subjects were further divided into current smokers with severe asthma
      (CSA), ex-smokers with severe asthma (ESA) and non-smokers with severe asthma
      (NSA) to deepen the effect of active smoking. Clinical data, urine and sputum
      were obtained from severe asthma subjects. A bronchoscopy to obtain bronchial
      biopsy and brushing was performed in a subset of subjects. The main clinical data
      were analysed for each subset of subjects (urine-8-iso-PGF2alpha; IS
      transcriptomics; BB-transcriptomics; BBr-transcriptomics). Urinary 8-iso
      PGF2alpha was quantified using mass spectrometry. Sputum, bronchial biopsy and
      bronchial brushing were processed for mRNA expression microarray analysis.
      Urinary 8-iso-PGF2alpha was increased in SAs/ex, median (IQR) = 31.7 (24.5-44.7)
      ng/mmol creatinine, compared to SAn, median (IQR) = 26.6 (19.6-36.6) ng/mmol
      creatinine (p< 0.001), and in CSA, median (IQR) = 34.25 (24.4-47.7), vs. ESA,
      median (IQR) = 29.4 (22.3-40.5), and NSA, median (IQR) = 26.5 (19.6-16.6) ng/mmol
      creatinine (p = 0.004). Sputum mRNA expression of NOX2 was increased in SAs/ex
      compared to SAn (probe sets 203922_PM_s_at fold-change = 1.05 p = 0.006;
      203923_PM_s_at fold-change = 1.06, p = 0.003; 233538_PM_s_at fold-change = 1.06,
      p = 0.014). The mRNA expression of antioxidant enzymes were similar between the
      two severe asthma cohorts in all airway samples. NOS2 mRNA expression was
      decreased in bronchial brushing of SAs/ex compared to SAn (fold-change = -1.10; p
      = 0.029). NOS2 mRNA expression in bronchial brushing correlated with FeNO
      (Kendal's Tau = 0.535; p< 0.001). From clinical and inflammatory analysis, FeNO
      was lower in CSA than in ESA in all the analysed subject subsets (p< 0.01)
      indicating an effect of active smoking. Results about FeNO suggest its clinical
      limitation, as inflammation biomarker, in severe asthma active smokers. These
      data provide evidence of greater systemic oxidative stress in severe asthma
      smokers as reflected by a significant changes of NOX2 mRNA expression in the
      airways, together with elevated urinary 8-iso-PGF2alpha in the smokers/ex-smokers
      group. Trial registration ClinicalTrials.gov-Identifier: NCT01976767.

PMID- 30240404
TI  - Thermal exposure of adult Chinook salmon and steelhead: Diverse behavioral
      strategies in a large and warming river system.
AB  - Rising river temperatures in western North America have increased the energetic
      costs of migration and the risk of premature mortality in many Pacific salmon
      (Oncorhynchus spp.) populations. Predicting and managing risks for these
      populations requires data on acute and cumulative thermal exposure, the spatio
      temporal distribution of adverse conditions, and the potentially mitigating
      effects of cool-water refuges. In this study, we paired radiotelemetry with
      archival temperature loggers to construct continuous, spatially-explicit thermal
      histories for 212 adult Chinook salmon (O. tshawytscha) and 200 adult steelhead
      (O. mykiss). The fish amassed ~500,000 temperature records (30-min intervals)
      while migrating through 470 kilometers of the Columbia and Snake rivers en route
      to spawning sites in Idaho, Oregon, and Washington. Spring- and most summer-run
      Chinook salmon migrated before river temperatures reached annual highs; their
      body temperatures closely matched ambient temperatures and most had thermal
      maxima in the lower Snake River. In contrast, many individual fall-run Chinook
      salmon and most steelhead had maxima near thermal tolerance limits (20-22 
      degrees C) in the lower Columbia River. High temperatures elicited extensive use
      of thermal refuges near tributary confluences, where body temperatures were ~2-10
      degrees C cooler than the adjacent migration corridor. Many steelhead used
      refuges for weeks or more whereas salmon use was typically hours to days,
      reflecting differences in spawn timing. Almost no refuge use was detected in a
      ~260-km reach where a thermal migration barrier may more frequently develop in
      future warmer years. Within population, cumulative thermal exposure was strongly
      positively correlated (0.88 <= r <= 0.98) with migration duration and
      inconsistently associated (-0.28 <= r <= 0.09) with migration date. All four
      populations have likely experienced historically high mean and maximum
      temperatures in recent years. Expected responses include population-specific
      shifts in migration phenology, increased reliance on patchily-distributed thermal
      refuges, and natural selection favoring temperature-tolerant phenotypes.

PMID- 30240405
TI  - Role of altered proteostasis network in chronic hypobaric hypoxia induced
      skeletal muscle atrophy.
AB  - BACKGROUND: High altitude associated hypobaric hypoxia is one of the cellular and
      environmental perturbation that alters proteostasis network and push the healthy
      cell towards loss of muscle mass. The present study has elucidated the robust
      proteostasis network and signaling mechanism for skeletal muscle atrophy under
      chronic hypobaric hypoxia (CHH). METHODS: Male Sprague Dawley rats were exposed
      to simulated hypoxia equivalent to a pressure of 282 torr for different durations
      (1, 3, 7 and 14 days). After CHH exposure, skeletal muscle tissue was excised
      from the hind limb of rats for biochemical analysis. RESULTS: Chronic hypobaric
      hypoxia caused a substantial increase in protein oxidation and exhibited a
      greater activation of ER chaperones, glucose-regulated protein-78 (GRP-78) and
      protein disulphide isomerase (PDI) till 14d of CHH. Presence of oxidized proteins
      triggered the proteolytic systems, 20S proteasome and calpain pathway which were
      accompanied by a marked increase in [Ca2+]. Upregulated Akt pathway was observed
      upto 07d of CHH which was also linked with enhanced glycogen synthase kinase
      3beta (GSk-3beta) expression, a negative regulator of Akt. Muscle-derived
      cytokines, tumor necrosis factor-alpha (TNF-alpha), interferon-Upsilon (IFN-(c))
      and interleukin-1beta (IL-1beta) levels significantly increased from 07d onwards.
      CHH exposure also upregulated the expression of nuclear factor kappa-B (NF
      kappaB) and E3 ligase, muscle atrophy F-box-1 (Mafbx-1/Atrogin-1) and MuRF-1
      (muscle ring finger-1) on 07d and 14d. Further, severe hypoxia also lead to
      increase expression of ER-associated degradation (ERAD) CHOP/ GADD153, Ub
      proteasome and apoptosis pathway. CONCLUSIONS: The disrupted proteostasis network
      was tightly coupled to degradative pathways, altered anabolic signaling,
      inflammation, and apoptosis under chronic hypoxia. Severe and prolonged hypoxia
      exposure affected the protein homeostasis which overwhelms the muscular system
      and tends towards skeletal muscle atrophy.

PMID- 30240406
TI  - Cost-effectiveness of using a rapid diagnostic test to screen for human African
      trypanosomiasis in the Democratic Republic of the Congo.
AB  - New rapid diagnostic tests (RDTs) for screening human African trypanosomiasis
      (HAT) have been introduced as alternatives to the card agglutination test for
      trypanosomiasis (CATT). One brand of RDT, the SD BIOLINE HAT RDT has been shown
      to have lower specificity but higher sensitivity than CATT, so to make a rational
      choice between screening strategies, a cost-effectiveness analysis is a key
      element. In this paper we estimate the relative cost-effectiveness of CATT and
      the RDT when implemented in the Democratic Republic of the Congo (DRC). Data on
      the epidemiological parameters and costs were collected as part of a larger
      study. These data were used to model three different diagnostic algorithms in
      mobile teams and fixed health facilities, and the relative cost-effectiveness was
      measured as the average cost per case diagnosed. In both fixed facilities and
      mobile teams, screening of participants using the SD BIOLINE HAT RDT followed by
      parasitological confirmation had a lower cost-effectiveness ratio than in
      algorithms using CATT. Algorithms using the RDT were cheaper by 112.54 (33.2%)
      and 88.54 (32.92%) US dollars per case diagnosed in mobile teams and fixed health
      facilities respectively, when compared with algorithms using CATT. Sensitivity
      analysis demonstrated that these conclusions were robust to a number of
      assumptions, and that the results can be scaled to smaller or larger facilities,
      and a range of prevalences. The RDT was the most cost-effective screening test in
      all realistic scenarios and detected more cases than CATT. Thus, on this basis,
      the SD BIOLINE HAT RDT could be considered as the most cost-effective option for
      use in routine screening for HAT in the DRC.

PMID- 30240407
TI  - Improved production of polysaccharides in Ganoderma lingzhi mycelia by plasma
      mutagenesis and rapid screening of mutated strains through infrared spectroscopy.
AB  - As a traditional Chinese medicine, Ganoderma lingzhi has attracted increasing
      attention for both scientific research and medical application. In this work, in
      order to improve the production of polysaccharides from an original wide-type
      (WT) strain (named "RWY-0") of Ganoderma lingzhi, we applied atmospheric-pressure
      dielectric barrier discharge (DBD) nonthermal plasma to the protoplasts of RWY-0
      for mutagenesis treatment. Through a randomly amplified polymorphic DNA (RAPD)
      assay, at least 10 mutagenic strains were confirmed. They also showed different
      mycelium characteristics in terms of shape, color, size and biomass in liquid
      fermentation. The mutant strains were examined by infrared spectroscopy, and
      based on the established near-infrared (NIR) quantification model, the
      polysaccharide contents in these mutants were quantitatively evaluated. As a
      result, we found that the Ganoderma polysaccharide contents in some of the mutant
      strains were significantly changed compared with that of the original WT strain.
      The polysaccharide content of RWY-1 G. lingzhi was considerably higher than that
      of the WT strain, with an increase of 25.6%. Thus, this preliminary work
      demonstrates the extension of the plasma mutagenesis application in acquiring
      polysaccharide-enhanced Ganoderma lingzhi mutants and shows the usefulness of NIR
      spectroscopy in the rapid screening of mutagenic strains for other important
      ingredients.

PMID- 30240408
TI  - Policy, law and post-abortion care services in Kenya.
AB  - BACKGROUND: Unsafe abortion is still a leading cause of maternal death in most
      Sub-Saharan African countries. Post-abortion care (PAC) aims to minimize
      morbidity and mortality following unsafe abortion, addressing incomplete abortion
      by treating complications, and reducing possible future unwanted pregnancies by
      providing contraceptive advice. In this article, we draw on data from PAC service
      providers and patients in Kenya to illustrate how the quality of PAC in
      healthcare facilities is impacted by law and government policy. METHODS: A cross
      sectional design was used for this study, with in-depth interviews conducted to
      collect qualitative data from PAC service providers and seekers in healthcare
      facilities. Data were analyzed both deductively and inductively, with diverse sub
      themes related to specific components of PAC quality. RESULTS: The provision of
      quality PAC in healthcare facilities in Kenya is still low, with access hindered
      by restrictions on abortion. Negative attitudes towards abortion result in the
      continued undirected self-administration of abortifacients. Intermittent service
      interruptions through industrial strikes and inequitable access to care also
      drive unsafe terminations. Poor PAC service availability and lack of capacity to
      manage complications in primary care facilities result in multiple referrals and
      delays in care following abortion, leading to further complications. Inefficient
      infection control exposes patients and caregivers to unrelated infections within
      facilities, and the adequate provision of contraception is a continued challenge.
      DISCUSSION: Legal, policy and cultural restrictions to access PAC increase the
      level of complications. In Kenya, there is limited policy focus on PAC,
      especially at primary care level, and no guidelines for health providers to
      provide legal, safe abortion. Discrimination at the point of care discourages
      women from presenting for care, and discourages providers from freely offering
      post-abortion contraceptive guidance and services. Poor communication between
      facilities and communities continues to result in delayed care and access-related
      discrimination. CONCLUSION: Greater emphasis should be placed on the prevention
      of unsafe abortion and improved access to post-abortion care services in
      healthcare facilities. There is a definite need for service guidelines for this
      to occur.

PMID- 30240410
TI  - Calorie restriction does not influence oocyte quality in oocytes from POLG
      mitochondrial mutator mice.
AB  - It has recently been demonstrated that moderate adult onset caloric restriction
      (e.g. calorie restriction; CR) has a positive impact on female fertility in aged
      mice, due in large to preventing the age-associated decline in the quality of
      oocytes available for fertilization. The impact of CR on oocyte quality has been
      attributed, at least in part, to mitochondrial functions. In mitochondrial DNA
      (mtDNA) mutator mice (PolgD257A/D257A), which harbor a mutation in the
      proofreading mtDNA polymerase-gamma (POLG), mitochondrial mutations rapidly
      accumulate, resulting in a premature aging phenotype and female infertility. As
      CR has been shown to extend both lifespan and 'healthspan' as well as improve
      oocyte quality in aged mice, we investigated whether adult onset CR could improve
      oocyte quality in the POLG mouse. Female PolgD257A/D257A mice exhibited
      infertility based on an inability to produce litters through natural mating.
      Analysis of oocytes from 8-9-month-old PolgD257A/D257A mice on CR following
      hormone stimulation revealed no improvement in the number of oocytes ovulated.
      Furthermore, CR did not result in a greater percentage of metaphase II oocytes,
      with the majority of the oocytes prematurely arrested at the germinal vesicle
      stage. Finally, CR did not improve the abnormal mitochondrial distribution or
      pronounced defects in meiotic spindle assembly and chromosomal distribution
      observed in the ad libitum fed PolgD257A/D257A. Taken together, these data
      suggest that although CR benefits oocyte quality and fertility outcomes in
      naturally aged female mice, it does not sufficiently improve oocyte quality in
      PolgD257A/D257A.

PMID- 30240411
TI  - Biocontrol activity of Starmerella bacillaris yeast against blue mold disease on
      apple fruit and its effect on cider fermentation.
AB  - The reduction of chemical fungicides in agriculture has led to the use of
      microorganisms as biocontrol agents. Starmerella bacillaris is a non
      Saccharomyces yeast associated with overripe and botrytized grape berries
      microbiota. Its use has been proposed for wine fermentation because of yeast
      fructophilic character and high glycerol production. Recently, S. bacillaris has
      been demonstrated to possess antifungal activity against Botrytis cinerea on the
      grape. Penicillium expansum is the pathogen responsible for the blue mold rot,
      the most important postharvest disease of apples. These fruits are the raw
      material of the cider, an alcoholic beverage commonly produced using S.
      cerevisiae starter cultures. In this study 14 S. bacillaris strains have been
      studied to evaluate their postharvest antifungal activity against P. expansum on
      apples. Moreover, the fermentation performances in apple juice of these non
      Saccharomyces strains were tested, both in single-strain fermentation and in
      sequential fermentation, together with S. cerevisiae. Four S. bacillaris strains,
      able to significantly decrease blue mold rot symptoms and to increase glycerol
      content during fermentation have been selected to improve apple and cider
      quality.

PMID- 30240409
TI  - The cortical structure of functional networks associated with age-related
      cognitive abilities in older adults.
AB  - Age and cortical structure are both associated with cognition, but characterizing
      this relationship remains a challenge. A popular approach is to use functional
      network organization of the cortex as an organizing principle for post-hoc
      interpretations of structural results. In the current study, we introduce two
      complimentary approaches to structural analyses that are guided by a-priori
      functional network maps. Specifically, we systematically investigated the
      relationship of cortical structure (thickness and surface area) of distinct
      functional networks to two cognitive domains sensitive to age-related decline
      thought to rely on both common and distinct processes (executive function and
      episodic memory) in older adults. We quantified the cortical structure of
      individual functional network's predictive ability and spatial extent (i.e.,
      number of significant regions) with cognition and its mediating role in the age
      cognition relationship. We found that cortical thickness, rather than surface
      area, predicted cognition across the majority of functional networks. The default
      mode and somatomotor network emerged as particularly important as they appeared
      to be the only two networks to mediate the age-cognition relationship for both
      cognitive domains. In contrast, thickness of the salience network predicted
      executive function and mediated the age-cognition relationship for executive
      function. These relationships remained significant even after accounting for
      global cortical thickness. Quantifying the number of regions related to cognition
      and mediating the age-cognition relationship yielded similar patterns of results.
      This study provides a potential approach to organize and describe the apparent
      widespread regional cortical structural relationships with cognition and age in
      older adults.

PMID- 30240412
TI  - High frequency of mutations in 'dyshormonogenesis genes' in severe congenital
      hypothyroidism.
AB  - OBJECTIVE: Results of the screening of disease causative mutations in congenital
      hypothyroidism (CH) vary significantly, depending on the sequence strategy,
      patients' inclusion criteria and bioinformatics. The objective was to study the
      molecular basis of severe congenital hypothyroidism, using the next generation
      sequencing (NGS) and the recent guidelines for assessment of sequence variants.
      DESIGN: 243 patients with CH (TSH levels at neonatal screening or retesting
      greater than 90 mU/l) and 56 control subjects were included in the study.
      METHODS: A custom NGS panel targeting 12 CH causative genes was used for
      sequencing. The sequence variants were rated according to American College of
      Medical Genetics and Genomics (ACMG) guidelines. RESULTS: In total, 48
      pathogenic, 7 likely pathogenic and 57 variants of uncertain significance were
      identified in 92/243 patients (37.9%), while 4 variants of uncertain significance
      were found in 4/56 control subjects (7.1%). 13.1% (12/92) of the cases showed
      variants in 'thyroid dysgenesis' (TD) genes: TSHR, n = 6; NKX2-1, n = 2; NKX2-5,
      n = 1; PAX8, n = 3. The variants in 'dyshormonogenesis' (DH) genes were found in
      84.8% (78/92) of cases: TPO, n = 30; DUOX2, n = 24; TG, n = 8; SLC5A5, n = 3;
      SLC26A4, n = 6; IYD, n = 1. 8 patients showed oligonenic variants. The majority
      of variants identified in DH genes were monoallelic. CONCLUSIONS: In contrast to
      earlier studies demonstrating the predominance of TD in severe CH, the majority
      of variants identified in our study were in DH genes. A large proportion of
      monoallelic variants detected among DH genes suggests that non-mendelian
      mechanisms may play a role in the development of CH.

PMID- 30240413
TI  - MYB1 transcription factor is a candidate responsible for red root skin in radish
      (Raphanus sativus L.).
AB  - Root skin color is one of the economically important traits in radish (Raphanus
      sativus), and the pigmentation in red skin varieties is largely attributable to
      anthocyanin accumulation. Pelargonidin was found as a major anthocyanin pigment
      accumulated in the sub-epidermal layer of red radish roots. In the 20 F2
      population generated from the F1 with red root skins, root skins with red and
      white colors segregated in a 3:1 ratio. Additionally, a test cross between a red
      F3 individual and a white skin individual gave rise to 1:1 segregation of red and
      white, indicating that the root skin color of radish is determined by a single
      locus and red color is dominant over white. We performed association mapping for
      root skin color using SNPs obtained from RNA-seq analysis. Segregation analysis
      on the 152 F3 test-cross population revealed an RsMyb1 transcription factor as a
      candidate gene to determine root skin color. A PCR marker based on the
      polymorphism within 2 kb of RsMyb1 was developed and tested on 12 and 152
      individuals from F2 and F3 test cross populations, respectively, and red and
      white root skin colors were completely distinguished corresponding to the
      genotypes. Expression levels of RsMyb1 in red or purple root cultivars were
      significantly higher than in white root cultivars. These findings suggest that
      RsMyb1 is a crucial determinant for anthocyanin biosynthesis in radish roots, and
      the molecular marker developed in this study will be useful for marker-assisted
      selection for red skin individuals at early seedling stages.

PMID- 30240414
TI  - Correction: Population Distribution Analyses Reveal a Hierarchy of Molecular
      Players Underlying Parallel Endocytic Pathways.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0100554.].

PMID- 30240415
TI  - Correction: FAS-associated factor-1 positively regulates type I interferon
      response to RNA virus infection by targeting NLRX1.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1006398.].

PMID- 30240416
TI  - The impact of Joint Commission International accreditation on time periods in the
      operating room: A retrospective observational study.
AB  - The Joint Commission International (JCI) is responsible for upholding standards
      in healthcare and organizations in compliance receive accreditation. JCI requires
      quality improvement on patient safety goals, but requirements may prolong the
      total procedure/surgery time and reduce efficiency. Here, we evaluate the impact
      of JCI requirements on time periods in the operating room. We included patients
      who received elective and emergency surgeries under general anesthesia at
      Juntendo University Hospital between December 2014 and June 2016. Patients were
      classified as before and after JCI accreditation on December 12, 2015. The
      primary outcome was total procedure/surgery time. Secondary outcomes include five
      time periods comprising the total procedure/surgery time: pre-anesthesia time,
      anesthesia induction time, procedure/surgery time, anesthesia awareness time and
      post-anesthesia time. We compared these time periods between patients before and
      after JCI accreditation and patients were matched for age, sex and the specific
      type of surgery. Although total procedure/surgery time did not change
      significantly, pre-anesthesia time significantly increased (8.2 +/- 6.9 minutes
      vs. 8.5 +/- 6.9 minutes, before vs. after JCI, respectively, p = 0.028) and
      anesthesia induction time significantly decreased (34.4 +/- 16.1 minutes vs. 33.6
      +/- 15.4 minutes, before vs. after JCI, respectively, p = 0.037) after JCI
      accreditation. Other secondary study outcomes did not change significantly.
      Quality improvement initiatives associated with time periods in the operating
      room can be achieved without undermining efficiency.

PMID- 30240417
TI  - Effectiveness of short message services and voice call interventions for
      antiretroviral therapy adherence and other outcomes: A systematic review and meta
      analysis.
AB  - BACKGROUND: The potential of using mobile phone technologies to improve
      antiretroviral therapy (ART) adherence has provided a new facet to human
      immunodeficiency virus (HIV) research. The quality of evidence and the strength
      of recommendations of existing reviews, however, do not adequately support large
      scale adoption of the intervention. This review adopted broad selection criteria
      to include all mobile phone-based interventions designed to improve patient's
      adherence to ART. METHODS: We performed a systematic review and meta-analysis of
      randomized controlled trials and quasi-experimental studies. PUBMED, MEDLINE,
      EMBASE, PsychINFO, Cochrane Central Register of Controlled Trials (CENTRAL),
      CINAHL, AMED and Web of Science were searched. Online abstracts archives of
      relevant conference proceedings and trial registries were also searched. Thirty
      Five (35) full-text articles were assessed for eligibility. Included studies were
      conducted in high, low and middle-income countries and reported ART adherence
      interventions delivered by mobile phones (standard or smartphones) in the form of
      voice calls, interactive voice response calls (IVR), and short message service
      (SMS). RESULTS: Thirteen (13) studies met the inclusion criteria, and 11 were
      used in the meta-analysis. Intervention characteristics of included studies
      ranged from mobile phone functionalities to provision of study phones to
      participants. SMS and voice call contents were tailored to participants' specific
      adherence needs. Mobile SMS interventions improved adherence to ART compared with
      control conditions (OR, 95% CI = 1.59, 1.27-1.98). In subgroup analysis, only
      scheduled SMS was significant whereas triggered SMS had no effect on adherence to
      ART. Mobile voice calls did not significantly increase adherence to ART. The
      interventions were highly rated by > 90% of participants in the studies that
      reported on the experiences and satisfaction with the intervention. CONCLUSION:
      Scheduled mobile phone text-messaging have demonstrated significant improvement
      in adherence to ART. Mobile SMS adherence interventions that allow for two-way
      communication may, however, be more acceptable than standalone SMS reminders,
      which are seen to be intrusive, producing habituation and response fatigue. Voice
      calls and triggered SMS functionalities do not have a significant effect on
      adherence to ART although there is a higher preference for voice functionality
      over SMS especially in limited-resource and low-literacy settings. Further
      exploration of the mobile voice functionality and its possible combination with
      scheduled SMS functionality is recommended. Evidence provided in this study will
      guide the implementation of mobile phone intervention to improve adherence to
      ART, by addressing practical challenges that could militate against scalability
      especially in resource limited settings.

PMID- 30240418
TI  - Why do ambulance services have different non-transport rates? A national cross
      sectional study.
AB  - BACKGROUND: Some patients calling ambulance services (known as Emergency Medical
      Services internationally) are not transported to hospital. In England, national
      ambulance quality indicators show considerable variation in non-transport rates
      between the ten large regional ambulance services. The aim of this study was to
      explain variation between ambulance services in two types of non-transport:
      discharge at scene and telephone advice. METHODS: Mixed model logistic
      regressions using one month of data (November 2014) from the Computer Aided
      Despatch systems of the ten large regional ambulance services in England.
      RESULTS: 41% (251 677/615 815) of patients calling ambulance services were not
      transported to hospital. Most were discharged at scene after attendance by an
      ambulance (29% n = 182 479) and a small percentage were given telephone advice
      (7% n = 40 679). Discharge at scene rates varied by patient-level factors e.g.
      they were higher for elderly patients, where the reason for calling was falls,
      and for patients attended by paramedics with extended skills. These patient-level
      factors did not explain variation between ambulance services. After adjustment
      for patient-level factors, the following ambulance service level factors
      explained variation in discharge at scene rates: proportion of patients attended
      by paramedics with extended skills (odds ratio 1.05 (95% CI 1.04, 1.07)), the
      perception of ambulance service staff that paramedics with extended skills were
      established and valued within the workforce (odds ratio 1.84 (1.45, 2.33), and
      the perception of ambulance service staff that senior management viewed non
      transport as risky (odds ratio 0.78 (0.63, 0.98)). Variation in telephone advice
      rates could not be explained. CONCLUSIONS: Variation in discharge at scene rates
      was explained by differences in workforce configuration and managerial
      motivation, factors that are largely modifiable by ambulance services.

PMID- 30240420
TI  - User experience of controlling the DEKA Arm with EMG pattern recognition.
AB  - INTRODUCTION: A commercially available EMG Pattern Recognition (EMG-PR) control
      system was adapted to interface with the multi-degree of freedom (DOF) DEKA Arm.
      PURPOSE: To describe users' experience of controlling the DEKA Arm using EMG-PR.
      METHODS: Sample: Twelve persons with upper limb amputation participated, 10 with
      transradial (TR), 2 with transhumeral (TH) level amputation. Ten were male, and
      11 were users of a prosthesis at baselines. Design: This was a two-part study
      consisting of in-laboratory prosthetic training (Part A) and up to 12 weeks of
      home use of the prosthesis (Part B). Data collection: Qualitative data were
      collected through open-ended survey questions and semi-structured interviews.
      Data Analysis: The study used a qualitative case series design with a constant
      comparative approach to identify common categories of experience. Coding
      categories were iteratively refined until saturation of categories was achieved.
      The data were organized in a primary category, major categories of experience,
      factors impacting experience, and broader contextual factors. RESULTS: Users had
      mixed perspectives on the desirability of the EMG-PR control system in
      combination with the DEKA Arm. Major aspects of user experience related to the
      system complexity, process of calibrating, and functional benefits. Factors
      influencing user experience included training and acclimation, fatigue,
      prosthesis design, technical issues and control changes. Broader contextual
      factors, both personal and environmental, also impacted users' experience.
      DISCUSSION/CONCLUSION: This study provided an in-depth description of user
      experience operating the DEKA Arm using EMG-PR control. The majority of
      participants expressed a preference for the controls of their personal prosthesis
      and controls rather than the iteration of EMG-PR controlled DEKA Arm used in this
      study. Most were positive about the future potential of EMG-PR as a control
      method. An understanding of patient experience will assist clinicians and
      patients choosing prosthetic options.

PMID- 30240419
TI  - Antiretroviral exposure and comorbidities in an aging HIV-infected population:
      The challenge of geriatric patients.
AB  - As HIV-infected adults on successful antiretroviral therapy (ART) are expected to
      have close to normal lifespans, they will increasingly develop age-related
      comorbidities. The objective of this cross-sectional study was to compare in the
      French Dat'AIDS cohort, the HIV geriatric population, aged 75 years and over, to
      the elderly one, aged from 50 to 74 years. As of Dec 2015, 16,436 subjects (43.8%
      of the French Dat'AIDS cohort) were aged from 50 to 74 (elderly group) and 572
      subjects (1.5%) were aged 75 and over (geriatric group). Durations of HIV
      infection and of ART were slightly but significantly different, median at 19 and
      18 years, and 15 and 16 years in the elderly and geriatric group, respectively.
      The geriatric group was more frequently at CDC stage C and had a lower nadir CD4.
      This group had been more exposed to first generation protease inhibitors and
      thymidine analogues. Despite similar virologic suppression, type of ART at the
      last visit significantly differed between the 2 groups: triple ART in 74% versus
      68.2%, ART >= 4 drugs in 4.7% versus 2.7%; dual therapy in 11.6% versus 16.4% in
      the elderly group and the geriatric group, respectively. In the geriatric group
      all co-morbidities were significantly more frequent, except dyslipidemia, 4.3% of
      the elderly group had >=4 co-morbidities versus18.4% in the geriatric group.
      Despite more co-morbidities and more advanced HIV infection the geriatric
      population achieve similar high rate of virologic suppression than the elderly
      population. A multidisciplinary approach should be developed to face the incoming
      challenge of aging HIV population.

PMID- 30240421
TI  - Activation of RHO-1 in cholinergic motor neurons competes with dopamine
      signalling to control locomotion.
AB  - The small GTPase RhoA plays a crucial role in the regulation of neuronal
      signalling to generate behaviour. In the developing nervous system RhoA is known
      to regulate the actin cytoskeleton, however the effectors of RhoA-signalling in
      adult neurons remain largely unidentified. We have previously shown that
      activation of the RhoA ortholog (RHO-1) in C. elegans cholinergic motor neurons
      triggers hyperactivity of these neurons and loopy locomotion with exaggerated
      body bends. This is achieved in part through increased diacylglycerol (DAG)
      levels and the recruitment of the synaptic vesicle protein UNC-13 to synaptic
      release sites, however other pathways remain to be identified. Dopamine, which is
      negatively regulated by the dopamine re-uptake transporter (DAT), has a central
      role in modulating locomotion in both humans and C. elegans. In this study we
      identify a new pathway in which RHO-1 regulates locomotory behaviour by
      repressing dopamine signalling, via DAT-1, linking these two pathways together.
      We observed an upregulation of dat-1 expression when RHO-1 is activated and show
      that loss of DAT-1 inhibits the loopy locomotion phenotype caused by RHO-1
      activation. Reducing dopamine signalling in dat-1 mutants through mutations in
      genes involved in dopamine synthesis or in the dopamine receptor DOP-1 restores
      the ability of RHO-1 to trigger loopy locomotion in dat-1 mutants. Taken
      together, we show that negative regulation of dopamine signalling via DAT-1 is
      necessary for the neuronal RHO-1 pathway to regulate locomotion.

PMID- 30240422
TI  - Structural basis of antiviral activity of peptides from MPER of FIV gp36.
AB  - Feline immunodeficiency virus (FIV) is a naturally occurring Lentivirus causing
      acquired immunodeficiency syndrome in felines. It is considered a useful non
      primate model to study HIV infection, and to test anti-HIV vaccine. Similarly to
      HIV, FIV enters cells via a mechanism involving a surface glycoprotein named
      gp36. C8 is a short synthetic peptide corresponding to the residues
      770WEDWVGWI777 of gp36 membrane proximal external region (MPER). It elicits
      antiviral activity by inhibiting the fusion of the FIV and host cell membrane. C8
      is endowed with evident membrane binding property, inducing alteration of the
      phospholipid bilayer and membrane fusion. The presence and the position of
      tryptophan residues in C8 are important for antiviral activity: the C8 derivative
      C6a, obtained by truncating the N-terminal 770WE771 residues, exhibits conserved
      antiviral activity, while the C8 derivative C6b, derived from the truncation of
      the C-terminal 776WI777, is nearly inactive. To elucidate the structural factors
      that induce the different activity profiles of C6a and C6b, in spite of their
      similarity, we investigated the structural behaviour of the two peptides in
      membrane mimicking environments. Conformational data on the short peptides C6a
      and C6b, matched to those of their parent peptide C8, allow describing a
      pharmacophore model of antiviral fusion inhibitors. This includes the essential
      structural motifs to design new simplified molecules overcoming the
      pharmacokinetic and high cost limitations affecting the antiviral entry
      inhibitors that currently are in therapy.

PMID- 30240425
TI  - Survival and years of life lost in various aetiologies of dementia, mild
      cognitive impairment (MCI) and subjective cognitive decline (SCD) in Norway.
AB  - INTRODUCTION: Alzheimer's disease patients are reported to have higher survival
      rate compared to patients with vascular dementia or dementia with Lewy bodies.
      There is a paucity of studies investigating survival including persons with
      cognitive decline and dementia of various aetiologies. OBJECTIVES: We aimed to
      compare survival for patients with subjective cognitive decline, mild cognitive
      impairment, Alzheimer's disease, vascular dementia, mixed Alzheimer's/vascular
      dementia, dementia with Lewy bodies/Parkinson's disease, and other dementias
      compared to the general Norwegian population, taking into account the role of
      gender, cognitive function, function in everyday activities, comorbidity and
      education. METHODS: Patients (N = 4682), >=65 years, in the The Norwegian
      register of persons assessed for cognitive symptoms (NorCog) during 2009-2017
      were followed for mortality in the National Registry until January 2018. Flexible
      parametric survival models were applied to estimate relative survival, life
      expectancy and years of life lost for diagnostic groups compared with the general
      population. RESULTS: Patients with vascular dementia or dementia with Lewy
      bodies/Parkinson's had the shortest survival, followed by mixed dementia,
      Alzheimer's disease, unspecified dementia, mild cognitive impairment and
      subjective cognitive decline. At age 70 years, men with vascular dementia or
      dementia with Lewy bodies/Parkinson's had life expectancy of 4.7 years, which
      corresponded to 10.3 years of life lost compared to the general population. Years
      of life lost for other diagnoses were 10.0 years for mixed dementia, 9.2 years
      for Alzheimer's disease, 9.3 years for other dementias, 5.2 years for mild
      cognitive impairment and 2.2 years for subjective cognitive decline.
      Corresponding years of life lost in women were: 12.7 years, 10.5 years, 9.8
      years, 10.6 years, 7.8 years, and 2.6 years. Poor relative survival among
      dementia patients was associated with male gender, comorbidity, low cognitive
      function, and low function in activities of daily living. CONCLUSIONS: Compared
      with the general population, patients with subjective cognitive decline had no
      significant loss in life expectancy, while patients with mild cognitive
      impairment and all dementia subtypes had large losses, especially those with a
      diagnosis of vascular dementia or dementia with Lewy bodies/Parkinson's.

PMID- 30240426
TI  - Hyponatremia and the risk of kidney stones: A matched case-control study in a
      large U.S. health system.
AB  - Kidney stones impose a large and increasing public health burden. Previous
      studies showed that hyponatremia is associated with an increased risk of
      osteoporosis and bone fractures, which are also known to be associated with
      kidney stones. However, the relation between hyponatremia and kidney stones is
      not known. To assess the relation between hyponatremia and kidney stones, we
      designed a matched case-control study by using the electronic health records of
      the MedStar Health system with more than 3.4 million unique patient records as of
      March 2016. Data were extracted for clinical factors of patients with kidney
      stones (cases) and those without kidney stones (controls). Cases (n = 20,199) and
      controls (n = 20,199) were matched at a 1:1 ratio for age, sex, race, and the
      duration of encounter window. Case and control exposures for each of the
      hyponatremia variables were defined by serum sodium laboratory measurements
      reported within the encounter windows, and divided into 3 categories: prior
      hyponatremia, recent hyponatremia, and persistent hyponatremia. In the final
      conditional logistic models adjusted for potential confounders, the risk of
      kidney stones significantly increased in both recent and persistent hyponatremia
      categories: prior hyponatremia odds ratio (OR) 0.93 (95% confidence interval
      [CI], 0.86-1.00); recent hyponatremia OR 2.02 (95% CI, 1.76-2.32); persistent
      hyponatremia OR 6.25 (95% CI, 3.27-11.96). In conclusion, chronic persistent
      hyponatremia is a significant and clinically important risk factor for kidney
      stones in patients in the U.S.

PMID- 30240427
TI  - Asymmetrical hybridization and gene flow between Eisenia andrei and E. fetida
      lumbricid earthworms.
AB  - Uniformly pigmented Eisenia andrei (Ea) and striped E. fetida (Ef) lumbricid
      earthworms are hermaphrodites capable of self-fertilization, cross-fertilization,
      and asymmetrical hybridization. The latter was detected by genotyping of F1 and
      F2 progeny of the controlled Ea+Ef pairs by species-specific sequences of
      maternal mitochondrial COI genes and maternal/paternal nuclear S28 rRNA genes.
      Among F1offspring there were self-fertilized Ea (aAA), Ef (fFF), and cross
      fertilized fertile Ea-derived hybrids (aAF); the latter mated with Ea and gave
      new generation of Ea and hybrids, while mated with Ef gave Ea, Ef, Ea-derived
      hybrids and sterile Ef-derived hybrids (fFA). Coelomic fluid of Ea exhibits
      unique fluorescence spectra called here the M-fluorescence considered as a
      molecular biomarker of this species. Since similar fluorescence was detected also
      in some Ef (hypothetical hybrids?), the aim of present investigations was to
      identify the M-positive earthworms among families genotyped previously. It was
      assumed that factor/s responsible for metabolic pathways leading to production of
      undefined yet M-fluorophore might be encoded/controlled by alleles of
      hypothetical nuclear gene of Eisenia sp. segregating independently from species
      specific S28 rRNA nuclear genes, where 'MM' or 'Mm' alleles determine M
      positivity while 'mm' alleles determine M-negative phenotypes. Spectra of M
      fluorescence were detected in all 10 Ea (aAAMM) and 19 Ea-derived hybrids
      (aAFMm), three of four Ef-derived hybrids (fFAMm) and one 'atypical' Ef (fFFMm)
      among 13 Ef earthworms. Among progeny of 'atypical' M-positive Ef (fFFMm)
      reappeared 'typical' M-negative Ef (fFFmm), confirming such hypothesis.
      Alternatively, the M-fluorescence might be dependent on unknown gene products of
      vertically-transmitted Ea-specific symbiotic bacteria sexually transferred to the
      Ef partner. Hypotheses of intrinsic and external origin of M-fluorescence might
      complement each other. The presence/absence of M-fluorophore does not correspond
      with body pigmentation patterns; Ef-characteristic banding appeared in posterior
      parts of hybrids body. In conclusion, Ea/Ef hybridization may serve for further
      studies on bi-directional gene flow.

PMID- 30240424
TI  - Metabolic network reconstruction and phenome analysis of the industrial microbe,
      Escherichia coli BL21(DE3).
AB  - Escherichia coli BL21(DE3) is an industrial model microbe for the mass-production
      of bioproducts such as biofuels, biorefineries, and recombinant proteins.
      However, despite its important role in scientific research and biotechnological
      applications, a high-quality metabolic network model for metabolic engineering is
      yet to be developed. Here, we present the comprehensive metabolic network model
      of E. coli BL21(DE3), named iHK1487, based on the latest genome reannotation and
      phenome analysis. The metabolic model consists of 1,164 unique metabolites, 2,701
      metabolic reactions, and 1,487 genes. The model was validated and improved by
      comparing the simulation results with phenome data from phenotype microarray
      tests. Previous transcriptome profile data was incorporated during model
      reconstruction, and flux prediction was simulated using the model. iHK1487 was
      simulated to explore the metabolic features of BL21(DE3) such as broad spectrum
      amino acid utilization and enhanced flux through the upper glycolytic pathway and
      TCA cycle. iHK1487 will contribute to systematic understanding of cellular
      physiology and metabolism of E. coli BL21(DE3) and highlight its biotechnological
      applications.

PMID- 30240423
TI  - Chemoreceptor proteins in the Caribbean spiny lobster, Panulirus argus:
      Expression of Ionotropic Receptors, Gustatory Receptors, and TRP channels in two
      chemosensory organs and brain.
AB  - The spiny lobster, Panulirus argus, has two classes of chemosensilla representing
      "olfaction" and "distributed chemoreception," as is typical for decapod
      crustaceans. Olfactory sensilla are found exclusively on antennular lateral
      flagella and are innervated only by olfactory receptor neurons (ORNs) that
      project into olfactory lobes organized into glomeruli in the brain. Distributed
      chemoreceptor sensilla are found on all body surfaces including the antennular
      lateral flagella (LF) and walking leg dactyls (dactyls), and are innervated by
      both chemoreceptor neurons (CRNs) and mechanoreceptor neurons that project into
      somatotopically organized neuropils. Here, we examined expression of three
      classes of chemosensory genes in transcriptomes of the LF (with ORNs and CRNs),
      dactyls (with only CRNs), and brain of P. argus: Ionotropic Receptors (IRs),
      which are related to ionotropic glutamate receptors and found in all protostomes
      including crustaceans; Gustatory Receptors (GRs), which are ionotropic receptors
      that are abundantly expressed in insects but more restricted in crustaceans; and
      Transient Receptor Potential (TRP) channels, a diverse set of sensor-channels
      that include several chemosensors in diverse animals. We identified 108 IRs, one
      GR, and 18 homologues representing all seven subfamilies of TRP channels. The
      number of IRs expressed in the LF is far greater than in dactyls, possibly
      reflecting the contribution of receptor proteins associated with the ORNs beyond
      those associated with CRNs. We found co-receptor IRs (IR8a, IR25a, IR76b, IR93a)
      and conserved IRs (IR21a, IR40a) in addition to the numerous divergent IRs in the
      LF, dactyl, and brain. Immunocytochemistry showed that IR25a is expressed in
      ORNs, CRNs, and a specific type of cell located in the brain near the olfactory
      lobes. While the function of IRs, TRP channels, and the GR was not explored, our
      results suggest that P. argus has an abundance of diverse putative chemoreceptor
      proteins that it may use in chemoreception.

PMID- 30240428
TI  - Did aculeate silk evolve as an antifouling material?
AB  - Many of the challenges we currently face as an advanced society have been solved
      in unique ways by biological systems. One such challenge is developing strategies
      to avoid microbial infection. Social aculeates (wasps, bees and ants) mitigate
      the risk of infection to their colonies using a wide range of adaptations and
      mechanisms. These adaptations and mechanisms are reliant on intricate social
      structures and are energetically costly for the colony. It seems likely that
      these species must have had alternative and simpler mechanisms in place to ensure
      the maintenance of hygienic domicile conditions prior to the evolution of these
      complex behaviours. Features of the aculeate coiled-coil silk proteins are
      reminiscent of those of naturally occurring alpha-helical antimicrobial peptides
      (AMPs). In this study, we demonstrate that peptides derived from the aculeate
      silk proteins have antimicrobial activity. We reconstruct the predicted ancestral
      silk sequences of an aculeate ancestor that pre-dates the evolution of sociality
      and demonstrate that these ancestral sequences also contained peptides with
      antimicrobial properties. It is possible that the silks evolved as an antifouling
      material and facilitated the evolution of sociality. These materials serve as
      model materials for consideration in future biomaterial development.

PMID- 30240429
TI  - Predicting residential structures from open source remotely enumerated data using
      machine learning.
AB  - Having accurate maps depicting the locations of residential buildings across a
      region benefits a range of sectors. This is particularly true for public health
      programs focused on delivering services at the household level, such as indoor
      residual spraying with insecticide to help prevent malaria. While open source
      data from OpenStreetMap (OSM) depicting the locations and shapes of buildings is
      rapidly improving in terms of quality and completeness globally, even in settings
      where all buildings have been mapped, information on whether these buildings are
      residential, commercial or another type is often only available for a small
      subset. Using OSM building data from Botswana and Swaziland, we identified
      buildings for which 'type' was indicated, generated via on the ground
      observations, and classified these into two classes, "sprayable" and "not
      sprayable". Ensemble machine learning, using building characteristics such as
      size, shape and proximity to neighbouring features, was then used to form a model
      to predict which of these 2 classes every building in these two countries fell
      into. Results show that an ensemble machine learning approach performed
      marginally, but statistically, better than the best individual model and that
      using this ensemble model we were able to correctly classify >86% (using
      independent test data) of structures correctly as sprayable and not-sprayable
      across both countries.

PMID- 30240430
TI  - Correlation between elastic energy stored in an eye and visual field progression
      in glaucoma.
AB  - PURPOSE: To investigate whether the elastic energy stored in an eyeball at
      highest concavity (highest concavity energy; HCE), calculated with Corivs ST
      (CST, OCULUS), correlates with glaucomatous visual field (VF) progression.
      METHODS: 108 eyes from 70 primary open angle-glaucoma patients were studied. The
      HCE was calculated using CST parameters. For each eye, the mean total deviation
      (mTD) of the 52 test points in the 24-2 Humphrey Field Analyzer test pattern was
      calculated and the mTD progression rate was determined from eight reliable VFs.
      Eyes were subdivided into: subgroups with low- or high-whole eye motion maximal
      length (WEM-d) and subgroups with short- or long-time taken to reach WEM-d (WEM
      t), as measured with CST. The associations between mTD progression rate and HCE
      and other ocular/systemic parameters including age, Goldmann applanation
      tonometry based-intraocular pressure [GAT-IOP], and corneal hysteresis [CH] from
      the Ocular Response Analyzer (ORA(r), Reichert) were investigated using the
      linear mixed model. The optimal model to describe mTD progression rate was
      selected from all possible combinations according to the second order bias
      corrected Akaike Information Criterion index. RESULTS: Optimal models to describe
      mTD progression rate included: CH in the model for all eyes, age and HCE in the
      model for the WEM-d low group, HCE in the model for the WEM-t short group, mean
      GAT-IOP in the model for the WEM-d high group, and age in the model for the WEM-t
      long-group. CONCLUSIONS: HCE was associated with glaucomatous VF progression in
      eyes with minimal whole eye motion (low WEM-d and WEM-t subgroups).

PMID- 30240431
TI  - Is psychological stress a predisposing factor for amyotrophic lateral sclerosis
      (ALS)? An online international case-control study of premorbid life events,
      occupational stress, resilience and anxiety.
AB  - Psychological stress has been suggested to be relevant to the pathogenesis of
      neurodegenerative disorders, possibly via the generation of oxygen free radicals.
      We therefore sought to determine whether people with amyotrophic lateral
      sclerosis (ALS) had been subjected to more potentially stressful life events or
      occupations than controls, and whether they had differences in resilience or
      trait anxiety that would moderate their responses to these stressors. An online
      anonymous multilingual questionnaire was used to collect data on significant life
      events from people with and without ALS, using items from a modified Social
      Readjustment Rating Scale and from self-described significant events, which were
      combined to create a Life Events Inventory. Inventory scores were subdivided into
      0-20 years and 21-40 years age ranges, and for the preceding 2, 5 and 10 years.
      Respondents also rated levels of stress experienced during different occupations.
      Resilience was measured using the Connor-Davidson Resilience Scale, and trait
      anxiety with a modified Geriatric Anxiety Inventory. Scores were compared using
      nonparametric statistics. Data from 400 ALS (251 male, 149 female) and 450
      control (130 male, 320 female) respondents aged 40 years and over showed that
      Life Events Inventory scores were similar in male ALS respondents and controls,
      but lower in female ALS respondents than female controls for the preceding 5-year
      and 10-year periods. Occupational stress did not differ between ALS respondents
      and controls. Both male and female ALS respondents had higher resilience scores
      than controls. Anxiety scores did not differ between ALS and control groups. In
      conclusion, people with ALS reported no raised levels of potentially stressful
      premorbid life events or occupational stress, and did not have reduced levels of
      resilience, or increased levels of anxiety, that would augment the deleterious
      effects of stressors. On the contrary, ALS respondents had higher resilience than
      controls, though this conclusion relies on ALS respondents recalling their
      premorbid status. These results do not support the hypothesis that psychological
      stress from significant life events or occupational stress plays a role in the
      pathogenesis of ALS.

PMID- 30240432
TI  - Phosphate solubilizing bacteria with glucose dehydrogenase gene for phosphorus
      uptake and beneficial effects on wheat.
AB  - The aim of this study was to isolate, characterize and use phosphate solubilizing
      bacteria to enhance the bioavailability of insoluble Ca-phosphate for wheat
      plants. For this purpose, 15 phosphorus solubilizing bacteria (PSB) were isolated
      from wheat rhizospheric soils of Peshawar and southern Punjab region, Pakistan.
      These isolates were identified using light microscopy and 16S rRNA gene. Among
      the isolated bacteria, two strains (Pseudomonas sp. MS16 and Enterobacter sp.
      MS32) were the efficient P solubilizers based on their P solubilization activity
      determined qualitatively (solubilization index 3.2-5.8) as well as quantitatively
      (136-280 MUg mL-1). These two strains produced indole-3-acetic acid (25.6-28.1
      MUg mL-1), gibberellic acid (2.5-11.8), solubilized zinc compounds (SI 2.8-3.3)
      and showed nitrogenase and 1-Aminocyclopropane-1-carboxylic acid deaminase
      activity in vitro. Phosphate solubilization activity of Pseudomonas sp. MS16 was
      further validated by amplification, sequencing and phylogenetic analysis of
      glucose dehydrogenase (gcd) gene (LT908484) responsible for P solubilization.
      Response Surface Methodology for large-scale production was used to find optimal
      conditions (Temperature 22.5 degrees C, pH 7) for P solubilization. Glucose was
      found to support higher P solubilization in vitro. In an in vitro experiment, PSB
      treated wheat seedlings improved germination and seedling vigor (11% increases)
      as compared to un-inoculated control. Rhizoscanning of these seedlings showed an
      increase in various root growth parameters. Wheat inoculation with selected
      strain MS16 showed pronounced effect on grain yield in pot (38.5% increase) and
      field (17-18% increase) experiments compared to non-inoculated control. Root
      colonization by PSB through Florescent in situ Hybridization and Confocal Laser
      Scanning Microscopy confirmed their rhizosphere competence in soil. BOX-PCR
      confirmed the re-isolated colonies of Pseudomonas sp. MS16. The results indicated
      that gluconic acid producing Pseudomonas sp. MS16 from un-explored soils may be
      cost effective and environment friendly candidate to improve plant growth and
      phosphorous uptake by wheat plants.

PMID- 30240433
TI  - Differences in gene expression profiles for subcutaneous adipose, liver, and
      skeletal muscle tissues between Meishan and Landrace pigs with different backfat
      thicknesses.
AB  - Backfat thickness is one of the most important traits of commercially raised
      pigs. Meishan pigs are renowned for having thicker backfat than Landrace pigs. To
      examine the genetic factors responsible for the differences, we first produced
      female crossbred pig lines by mating Landrace (L) * Large White (W) * Duroc (D)
      females (LWD) with Landrace (L) or Meishan (M) boars (i.e., LWD * L = LWDL for
      Landrace offspring and LWD * M = LWDM for the Meishan offspring). We confirmed
      that LWDM pigs indeed had a thicker backfat than LWDL pigs. Next, we performed
      gene expression microarray analysis in both genetic lines to examine
      differentially expressed genes (DEGs) in energy metabolism-related tissues,
      subcutaneous adipose (fat), liver, and longissimus dorsi muscle tissues. We
      analyzed the annotation of DEGs (2-fold cutoff) to functionally categorize them
      by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The number
      of DEGs in muscle tissues of both lines was much less than that in fat and liver
      tissues, indicating that DEGs in muscle tissues may not contribute much to
      differences in backfat thickness. In contrast, several genes related to muscle
      (in fat tissue) and lipid metabolism (in liver tissue) were more upregulated in
      LWDM pigs than LWDL pigs, indicating that those DEGs might be responsible for
      differences in backfat thickness. The different genome-wide gene expression
      profiles in the fat, liver, and muscle tissues between genetic lines can provide
      useful information for pig breeders.

PMID- 30240434
TI  - Sex differences in vocal communication of freely interacting adult mice depend
      upon behavioral context.
AB  - Ultrasonic vocalizations (USVs) are believed to play a critical role in mouse
      communication. Although mice produce USVs in multiple contexts, signals emitted
      in reproductive contexts are typically attributed solely to the male mouse. Only
      recently has evidence emerged showing that female mice are also vocally active
      during mixed-sex interactions. Therefore, this study aimed to systematically
      quantify and compare vocalizations emitted by female and male mice as the animals
      freely interacted. Using an eight-channel microphone array to determine which
      mouse emitted specific vocalizations during unrestrained social interaction, we
      recorded 13 mixed-sex pairs of mice. We report here that females vocalized
      significantly less often than males during dyadic interactions, with females
      accounting for approximately one sixth of all emitted signals. Moreover, the
      acoustic features of female and male signals differed. We found that the
      bandwidths (i.e., the range of frequencies that a signal spanned) of female
      emitted signals were smaller than signals produced by males. When examining how
      the frequency of each signal changed over time, the slopes of male-emitted
      signals decreased more rapidly than female signals. Further, we revealed notable
      differences between male and female vocal signals when the animals were
      performing the same behaviors. Our study provides evidence that a female mouse
      does in fact vocalize during interactions with a male and that the acoustic
      features of female and male vocalizations differ during specific behavioral
      contexts.

PMID- 30240435
TI  - Biologically anchored knowledge expansion approach uncovers KLF4 as a novel
      insulin signaling regulator.
AB  - One of the biggest challenges in analyzing high throughput omics data in
      biological studies is extracting information that is relevant to specific
      biological mechanisms of interest while simultaneously restricting the number of
      false positive findings. Due to random chances with numerous candidate targets
      and mechanisms, computational approaches often yield a large number of false
      positives that cannot easily be discerned from relevant biological findings
      without costly, and often infeasible, biological experiments. We here introduce
      and apply an integrative bioinformatics approach, Biologically Anchored Knowledge
      Expansion (BAKE), which uses sequential statistical analysis and literature
      mining to identify highly relevant network genes and effectively removes false
      positive findings. Applying BAKE to genomic expression data collected from mouse
      (Mus musculus) adipocytes during insulin resistance progression, we uncovered the
      transcription factor Krueppel-like Factor 4 (KLF4) as a regulator of early
      insulin signaling. We experimentally confirmed that KLF4 controls the expression
      of two key insulin signaling molecules, the Insulin Receptor Substrate 2 (IRS2)
      and Tuberous Sclerosis Complex 2 (TSC2).

PMID- 30240436
TI  - Adherence to hospital nutritional status monitoring and reporting guidelines.
AB  - AIMS OF THE STUDY: Despite the widespread existence of guidelines regarding
      undernutrition monitoring and reporting, there is scarce information whether they
      are followed. We aimed to evaluate the adherence to guidelines regarding
      undernutrition monitoring and reporting as well as their determinants in a
      university hospital. METHODS: Retrospective analysis of discharged patients with
      data on Nutritional Risk Screening score (NRS-2002) from the department of
      internal medicine of the Lausanne University Hospital for years 2013-14.
      Adherence to the hospital monitoring guidelines, i.e.: 1) discharged patients
      with NRS-2002 score>=3 should have prealbumin levels measured, and 2) discharged
      patients with prealbumin levels<0.20 g/l should be rechecked 7 days afterwards,
      was assessed. Reporting of nutritionally 'at-risk' status in the discharge letter
      was also assessed. Multivariable logistic regression was used to examine
      potential determinants of adherence to guidelines. RESULTS: Of the 2,539
      discharged patients with NRS-2002 data, 1,605 (63.0%) were nutritionally 'at
      risk'. Complete adherence to the monitoring guideline was observed in 238 (14.8%)
      of 'at-risk' patients. After multivariable analysis, adherence to the first step
      of monitoring guideline was associated with older age (>= 80 years) [OR (95% CI):
      2.03 (1.29-3.18)], high comorbidity index [1.36 (1.05-1.77)], and nutritional
      management [5.57 (4.38-7.07)]. Nutritional management was also associated with
      adherence to the second step of monitoring [3.98 (2.33-6.78)]. Adherence to the
      reporting guideline was observed in 343 (21.4%) of 'at-risk' patients.
      Multivariable analysis showed that adherence to the reporting guideline was
      associated with NRS-2002 score>4 [1.97 (1.47-2.64)], nutritional management [3.80
      (2.85-5.07)], and adherence to the monitoring guideline [3.33 (2.35-4.71)].
      CONCLUSIONS: Our results show a poor adherence to guidelines regarding
      undernutrition monitoring and reporting, possibly due to lack of training, staff,
      and time.

PMID- 30240437
TI  - Expression of combinatorial immunoglobulins in macrophages in the tumor
      microenvironment.
AB  - Recent evidence indicates the presence of macrophage subpopulations that express
      the TCRalphabeta in chronic inflammatory diseases such as tuberculosis and
      atherosclerosis and in the tumor microenvironment. Here, we demonstrate that a
      second subpopulation of macrophages expresses rearranged heavy and light chain
      immunoglobulins. We identify immunoglobulin expression in human and murine
      monocytes, in ex vivo differentiated macrophages and macrophages from the tumor
      microenvironment of five randomly selected distinct human tumor entities. The
      immunoglobulin heavy and light chains are expressed in a small macrophage
      subfraction (~3-5%) as combinatorial and individual-specific immune receptors.
      Using Sanger sequencing and deep sequencing, we routinely find markedly
      restricted Ig repertoires in monocytes/macrophages compared to normal B cells.
      Furthermore, we report the complete Ig heavy and light chain sequences of a fully
      functional immunoglobulin from a single tumor-associated macrophage. These
      results demonstrate that Ig expression is a defining feature of monocytes and
      also macrophages in the tumor microenvironment and thus reveal an as yet
      unrecognized modus operandi of host defense in professional phagocytes.

PMID- 30240438
TI  - ALG-2 participates in recovery of cells after plasma membrane damage by
      electroporation and digitonin treatment.
AB  - The calcium binding protein ALG-2 is upregulated in several types of cancerous
      tissues and cancer cell death may be a consequence of ALG-2 downregulation. Novel
      research suggests that ALG-2 is involved in membrane repair mechanisms, in line
      with several published studies linking ALG-2 to processes of membrane remodeling
      and transport, which may contribute to the fitness of cells or protect them from
      damage. To investigate the involvement of ALG-2 in cell recovery after membrane
      damage we disrupted the PDCD6 gene encoding the ALG-2 protein in DT-40 cells and
      exposed them to electroporation. ALG-2 knock-out cells were more sensitive to
      electroporation as compared to wild type cells. This phenotype could be reversed
      by reestablishing ALG-2 expression confirming that ALG-2 plays an important role
      in cell recovery after plasma membrane damage. We found that overexpression of
      wild type ALG-2 but not a mutated form unable to bind Ca2+ partially protected
      HeLa cells from digitonin-induced cell death. Further, we were able to inhibit
      the cell protective function of ALG-2 after digitonin treatment by adding a
      peptide with the ALG-2 binding sequence of ALIX, which has been proposed to serve
      as the ALG-2 downstream target in a number of processes including cell membrane
      repair. Our results suggest that ALG-2 may serve as a novel therapeutic target in
      combination with membrane damaging interventions.

PMID- 30240440
TI  - Gi/o-coupled muscarinic receptors co-localize with GIRK channel for efficient
      channel activation.
AB  - G protein-gated inwardly rectifying K+ (GIRK) channel regulates cellular
      excitability upon activation of Gi/o-coupled receptors. In Gi/o-coupled
      muscarinic M2R, the intracellular third loop (i3) is known as a key domain for
      Gi/o coupling, because replacement of i3 of Gq-coupled muscarinic M1R with that
      of M2R enables the chimeric receptor (MC9) to activate the GIRK channel. In the
      present study, we showed that MC9, but not M1R, co-localizes with the GIRK
      channel and Galphai1 by Forster resonance energy transfer (FRET) analysis. When
      M1R was forced to stay adjacent to the channel through ligation with short
      linkers, M1R activated the GIRK channel. FRET analysis further suggested that the
      efficacy of channel activation is correlated with the linker length between M1R
      and the GIRK channel. The results show that co-localization is an important
      factor for activating the GIRK channel. In contrast, for MC9 and M2R, the GIRK
      channel was activated even when they were connected by long linkers, suggesting
      the formation of a molecular complex even in the absence of a linker. We also
      observed that replacement of 13 amino acid residues at the N-terminal end of i3
      of MC9 with those of M1R impaired the co-localization with the GIRK channel as
      well as channel activation. These results show that localization of the receptor
      near the GIRK channel is a key factor in efficiently activating the channel and
      that the N-terminal end of i3 of M2R plays an important role in co-localization.

PMID- 30240439
TI  - Condition-adaptive fused graphical lasso (CFGL): An adaptive procedure for
      inferring condition-specific gene co-expression network.
AB  - Co-expression network analysis provides useful information for studying gene
      regulation in biological processes. Examining condition-specific patterns of co
      expression can provide insights into the underlying cellular processes activated
      in a particular condition. One challenge in this type of analysis is that the
      sample sizes in each condition are usually small, making the statistical
      inference of co-expression patterns highly underpowered. A joint network
      construction that borrows information from related structures across conditions
      has the potential to improve the power of the analysis. One possible approach to
      constructing the co-expression network is to use the Gaussian graphical model.
      Though several methods are available for joint estimation of multiple graphical
      models, they do not fully account for the heterogeneity between samples and
      between co-expression patterns introduced by condition specificity. Here we
      develop the condition-adaptive fused graphical lasso (CFGL), a data-driven
      approach to incorporate condition specificity in the estimation of co-expression
      networks. We show that this method improves the accuracy with which networks are
      learned. The application of this method on a rat multi-tissue dataset and The
      Cancer Genome Atlas (TCGA) breast cancer dataset provides interesting biological
      insights. In both analyses, we identify numerous modules enriched for Gene
      Ontology functions and observe that the modules that are upregulated in a
      particular condition are often involved in condition-specific activities.
      Interestingly, we observe that the genes strongly associated with survival time
      in the TCGA dataset are less likely to be network hubs, suggesting that genes
      associated with cancer progression are likely to govern specific functions or
      execute final biological functions in pathways, rather than regulating a large
      number of biological processes. Additionally, we observed that the tumor-specific
      hub genes tend to have few shared edges with normal tissue, revealing tumor
      specific regulatory mechanism.

PMID- 30240441
TI  - Bronchovascular injury associated with clinically significant hemoptysis after CT
      guided core biopsy of the lung: Radiologic and histopathologic analysis.
AB  - OBJECTIVE: To evaluate bronchovascular injuries as the causative occurrence for
      clinically significant hemoptysis after percutaneous transthoracic needle biopsy
      (PTNB). MATERIALS AND METHODS: We included 111 consecutive patients who
      experienced hemoptysis after cone beam CT (CBCT)-guided PTNB from January 2014
      through January 2017. Clinically significant hemoptysis was defined as hemoptysis
      causing hemodynamic instability or oxygen desaturation greater than 10% of
      baseline. The lesion characteristics were evaluated on CT images. The penetration
      of bronchovascular structures along the trajectory of the introducer needle and
      potential penetration at the firing of the biopsy gun were assessed on CBCT
      images. The cutting injury of bronchovascular structures was histopathologically
      assessed in biopsy specimens. The associated factors for clinically significant
      hemoptysis were assessed using logistic regression analyses. RESULTS: Seventeen
      patients (15.3%; 95%CI, 9.7%-23.2%) had clinically significant hemoptysis. On
      univariate analysis, the open bronchus sign (P = .004), nodule consistency (P =
      .012), potential penetration of a pulmonary vessel or bronchus 1 mm or larger at
      firing (P = .008 and P = .038, respectively), and a cutting injury of a pulmonary
      vessel 1 mm or larger (P = .007) or a bronchial structure (P = .041) were
      associated with clinically significant hemoptysis. Multivariate analysis found
      the following significant associated factors: potential penetration of a
      pulmonary vessel 1 mm or larger at firing (OR, 3.874; 95%CI, 1.072-13.997; P =
      .039) and cutting injury of a pulmonary vessel 1 mm or larger (OR, 6.920; 95%CI,
      1.728-27.711; P = .006) or a bronchial structure (OR 4.604; 95%CI, 1.194-17.755;
      P = .027). CONCLUSION: Potential penetration and cutting injury of
      bronchovascular structures 1mm or larger at firing were independently associated
      with clinically significant hemoptysis after PTNB.

PMID- 30240444
TI  - Commentary on "The number of undocumented immigrants in the United States:
      Estimates based on demographic modeling with data from 1990-2016".
AB  - "The number of undocumented immigrants in the United States: Estimates based on
      demographic modeling with data from 1990-2016" by Fazel-Zarandi, Feinstein and
      Kaplan presents strikingly higher estimates of the unauthorized immigrant
      population than established estimates using the residual method. Fazel-Zarandi
      et. al.'s estimates range from a low or "conservative" number of 16.7 million
      unauthorized immigrants, to an "average" of 22.1 million, and to a high of 27.5
      million. The Pew Hispanic Center estimated the population at 11.3 million in
      2016, and the Department of Homeland Security (DHS) estimated it at 12.3 million.
      The new method shows much more rapid growth in unauthorized immigration during
      the 1990s and a substantially higher population in 2000 (13.3 million according
      to their "conservative" model) than Pew (8.6 million) and DHS (8.5 million). In
      this commentary, we explain that such an estimate for 2000 is implausible, as it
      suggests that the 2000 Census undercounted the unauthorized immigrant population
      by at least 42% in the 2000 Census, and it is misaligned with other demographic
      data. Fazel-Zarandi, Feinstein and Kaplan's model produces estimates that have a
      10 million-person range in 2016, far too wide to be useful for public policy
      purposes; their estimates are not benchmarked against any external data sources;
      and their model appears to be driven by assumptions about return migration of
      unauthorized immigrants during the 1990s. Using emigration rates from the
      binational Mexican Migration Project survey for the illegal border-crosser
      portion of the unauthorized population, we generate a 2000 unauthorized
      population estimate of 8.2 million-slightly below Pew and DHS's estimates-without
      changing other assumptions in the model. We conclude that this new model's
      estimates are highly sensitive to assumptions about emigration, and moreover,
      that the knowledge base about emigration in the unauthorized population during
      the 1990s is not well enough developed to support the model underlying their
      estimates.

PMID- 30240443
TI  - Abdominal aortic calcification can predict all-cause mortality and CV events in
      dialysis patients: A systematic review and meta-analysis.
AB  - BACKGROUND: Abdominal aortic calcification (AAC) has a pretty high incidence in
      dialysis patients and may be associated with their prognosis. AAC can be assessed
      by abdominal CT or X-ray. We determined to investigate whether the occurrence of
      AAC is associated with all-cause mortality and cardiovascular (CV) events in
      dialysis patients through this meta-analysis and systematic review. METHODS: A
      comprehensive literature search was conducted using the PubMed, Cochrane library,
      Embase, Medline databases to collect cohort studies investigating whether AAC is
      associated with all-cause mortality and CV events of patients, and we also
      searched gray articles and conferences abstracts. Meta-analysis was performed by
      STATA software. Pooled results were expressed as hazard ratio (HR) with
      corresponding 95% confidence intervals (CI). Fixed-effect models were used to
      pool the HR of each trial. RESULTS: 10 studies (2,724 dialysis patients) were
      identified. The presence of AAC was associated with increased risk for all-cause
      mortality among dialysis patients (HR, 2.84; 95% CI, 2.03-3.98; I2 = 9.8%; P =
      0.354). Meanwhile, there was an association between AAC and increased risk for
      all CV events (fatal and non-fatal) in patients (HR, 2.04; 95% CI, 1.51-2.76, I2
      = 44.6%; P = 0.125). 3 studies presented their endpoint as CV mortality, and the
      pooled HR was 2.46 (95%CI 1.38-4.40; I2 = 0.0%; P = 0.952). There were also 2
      studies that reported their primary endpoint as all-cause mortality and CV
      events, and the pooled HR was 5.72 (95% CI 3.24-10.10; I2 = 0.0%; P = 0.453).
      CONCLUSIONS: Among patients treated with dialysis, AAC is associated with adverse
      outcomes, including all-cause mortality and CV events (fatal and non-fatal). The
      abdominal X-ray or CT scan can be used as a useful added method to evaluate the
      patient's calcification. This may provide reasonable data for estimating the risk
      of adverse events in dialysis patients, which is helpful in guiding clinical
      treatment and improving the prognosis of dialysis patients.

PMID- 30240442
TI  - Type 2 diabetes genetic loci informed by multi-trait associations point to
      disease mechanisms and subtypes: A soft clustering analysis.
AB  - BACKGROUND: Type 2 diabetes (T2D) is a heterogeneous disease for which (1)
      disease-causing pathways are incompletely understood and (2) subclassification
      may improve patient management. Unlike other biomarkers, germline genetic markers
      do not change with disease progression or treatment. In this paper, we test
      whether a germline genetic approach informed by physiology can be used to
      deconstruct T2D heterogeneity. First, we aimed to categorize genetic loci into
      groups representing likely disease mechanistic pathways. Second, we asked whether
      the novel clusters of genetic loci we identified have any broad clinical
      consequence, as assessed in four separate subsets of individuals with T2D.
      METHODS AND FINDINGS: In an effort to identify mechanistic pathways driven by
      established T2D genetic loci, we applied Bayesian nonnegative matrix
      factorization (bNMF) clustering to genome-wide association study (GWAS) results
      for 94 independent T2D genetic variants and 47 diabetes-related traits. We
      identified five robust clusters of T2D loci and traits, each with distinct tissue
      specific enhancer enrichment based on analysis of epigenomic data from 28 cell
      types. Two clusters contained variant-trait associations indicative of reduced
      beta cell function, differing from each other by high versus low proinsulin
      levels. The three other clusters displayed features of insulin resistance:
      obesity mediated (high body mass index [BMI] and waist circumference [WC]),
      "lipodystrophy-like" fat distribution (low BMI, adiponectin, and high-density
      lipoprotein [HDL] cholesterol, and high triglycerides), and disrupted liver lipid
      metabolism (low triglycerides). Increased cluster genetic risk scores were
      associated with distinct clinical outcomes, including increased blood pressure,
      coronary artery disease (CAD), and stroke. We evaluated the potential for
      clinical impact of these clusters in four studies containing individuals with T2D
      (Metabolic Syndrome in Men Study [METSIM], N = 487; Ashkenazi, N = 509; Partners
      Biobank, N = 2,065; UK Biobank [UKBB], N = 14,813). Individuals with T2D in the
      top genetic risk score decile for each cluster reproducibly exhibited the
      predicted cluster-associated phenotypes, with approximately 30% of all
      individuals assigned to just one cluster top decile. Limitations of this study
      include that the genetic variants used in the cluster analysis were restricted to
      those associated with T2D in populations of European ancestry. CONCLUSION: Our
      approach identifies salient T2D genetically anchored and physiologically informed
      pathways, and supports the use of genetics to deconstruct T2D heterogeneity.
      Classification of patients by these genetic pathways may offer a step toward
      genetically informed T2D patient management.

PMID- 30240445
TI  - Health professionals' and researchers' perspectives on prenatal whole genome and
      exome sequencing: 'We can't shut the door now, the genie's out, we need to refine
      it'.
AB  - The Prenatal Assessment of Genome and Exomes (PAGE) project is a UK-wide study
      aiming to gain a better understanding of genetic variants causing developmental
      problems during pregnancy. A further aim of the study is to provide an evidence
      base for the introduction of prenatal whole genome and exome sequencing (PWGES)
      into prenatal diagnostics provided by the NHS, which is expected in 2018. This
      paper presents the findings of a qualitative interview study undertaken with 20
      health professionals and researchers involved in the PAGE project, and explores
      their implications for understandings of 'good practice' in the uses of prenatal
      genomics clinically. A number of critical issues are identified that will need to
      be addressed in the development of a model of good ethical practice for prenatal
      genomics: consent, management of expectations, return of results, and
      professional duties in the context of PWGES. The analysis presented identifies
      and illustrates a great deal of complexity and qualitative richness in these
      issues as they arise in the day-to-day work of genomics professionals. Inclusive,
      critical discussion of these findings, together with the findings from other
      empirical studies, normative analysis and scientific discoveries resulting from
      PAGE, will be required to inform the development of appropriate guidelines of
      good ethical practice that address the needs and concerns to be encountered in
      daily clinical practice.

PMID- 30240446
TI  - Polygenic risk scores for major depressive disorder and neuroticism as predictors
      of antidepressant response: Meta-analysis of three treatment cohorts.
AB  - There are currently no reliable approaches for correctly identifying which
      patients with major depressive disorder (MDD) will respond well to antidepressant
      therapy. However, recent genetic advances suggest that Polygenic Risk Scores
      (PRS) could allow MDD patients to be stratified for antidepressant response. We
      used PRS for MDD and PRS for neuroticism as putative predictors of antidepressant
      response within three treatment cohorts: The Genome-based Therapeutic Drugs for
      Depression (GENDEP) cohort, and 2 sub-cohorts from the Pharmacogenomics Research
      Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS (total patient
      number = 760). Results across cohorts were combined via meta-analysis within a
      random effects model. Overall, PRS for MDD and neuroticism did not significantly
      predict antidepressant response but there was a consistent direction of effect,
      whereby greater genetic loading for both MDD (best MDD result, p < 5*10-5 MDD-PRS
      at 4 weeks, beta = -0.019, S.E = 0.008, p = 0.01) and neuroticism (best
      neuroticism result, p < 0.1 neuroticism-PRS at 8 weeks, beta = -0.017, S.E =
      0.008, p = 0.03) were associated with less favourable response. We conclude that
      the PRS approach may offer some promise for treatment stratification in MDD and
      should now be assessed within larger clinical cohorts.

PMID- 30240447
TI  - Combined mineral-supplemented diet and exercise increases bone mass and strength
      after eight weeks and maintains increases after eight weeks detraining in adult
      mice.
AB  - Exercise has long-lasting benefits to bone mass and structural strength even
      after cessation. Combining exercise with a calcium- and phosphorus-supplemented
      diet increases cortical bone mineral content (BMC), area, and yield force more
      than exercise alone in adult mice. These increases could also be maintained after
      stopping exercise if the modified diet is maintained. It was hypothesized that
      combining exercise with a mineral-supplemented diet would lead to greater
      cortical BMC, area, and yield force immediately after a lengthy exercise program
      and after an equally long period of non-exercise (detraining) in adult mice.
      Male, 16-week old C57Bl/6 mice were assigned to 9 weight-matched groups-a
      baseline group, exercise and non-exercise groups fed a control or mineral
      supplemented diet for 8 weeks, exercise + detraining and non-exercise groups fed
      a control or mineral-supplemented diet for 16 weeks. Exercise + detraining
      consisted of 8 weeks of exercise followed by 8 weeks without exercise. The daily
      exercise program consisted of running on a treadmill at 12 m/min, 30 min/day.
      After 8 weeks, mice fed the supplemented diet had greater tibial cortical BMC and
      area, trabecular bone volume/tissue volume (BV/TV), bone mineral density (vBMD),
      yield force, and ultimate force than mice fed the control diet. Exercise
      increased cortical BMC and area only when coupled with the supplemented diet.
      After 16 weeks, both exercised and non-exercised mice fed the supplemented diet
      maintained greater tibial cortical BMC and area, trabecular BV/TV, vBMD, yield
      force, and ultimate force than mice fed the control diet. Combining exercise with
      a mineral-supplemented diet leads to greater bone mass and structural strength
      than exercise alone. These benefits remain after an equally long period of
      detraining. Long-term use of dietary mineral supplements may help increase and
      maintain bone mass with aging in adult mice.

PMID- 30240450
TI  - Correction: Enhancing radiosensitivity of melanoma cells through very high dose
      rate pulses released by a plasma focus device.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0199312.].

PMID- 30240449
TI  - Disease and economic burden for rare diseases in Taiwan: A longitudinal study
      using Taiwan's National Health Insurance Research Database.
AB  - BACKGROUND: High-cost orphan drugs are becoming increasingly available to treat
      rare diseases that affect a relatively small population. Little attention has
      been given to the prevalence of rare diseases and their health-related economic
      burden in Taiwan. OBJECTIVES: This study examined the national trends in the
      prevalence of rare diseases and their health-related economic burden (including
      medication costs) in Taiwan. METHODS: Rare disease-related claims data from 2003
      2014 (12 years) from the National Health Insurance Research Database were used in
      this study. We used a time series analysis to assess trends in the yearly rates
      of treated patients with rare diseases, overall healthcare use, and expenditures,
      including drugs. RESULTS: During the 12-year study period, the estimated
      prevalence of rare diseases increased from 10.57 to 33.21 per 100,000 population,
      an average rate of a 19.46% increase per year. Total health expenditures for
      treatment of rare diseases increased from US$18.65 million to US$137.44 million
      between 2003 and 2014, accounting for 0.68% of the total national health
      expenditures in 2014. Drug expenditures for treatment of rare diseases increased
      from US$13.24 million to US$121.98 million between 2003 and 2014, which accounted
      for 71.00% and 88.75% of the health expenditures for patients with rare diseases
      in 2003 and 2014, respectively. In 2014, we found a 20.43-fold difference in
      average health expenditures and a 69.46-fold difference in average drug
      expenditures between patients with rare diseases and the overall population.
      CONCLUSIONS: The prevalence of rare diseases and the related economic burden have
      grown substantially in Taiwan over the past 12 years, and these trends are likely
      to continue. Drug expenditures accounted for almost 90% of health expenditures
      for rare diseases. Further analyses are underway to examine the economic burden
      of individual rare diseases.

PMID- 30240448
TI  - Circulating monocyte subsets and heart failure prognosis.
AB  - Monocytes are a heterogeneous population of effector cells with key roles in
      tissue integrity restoration and maintenance. Here, we explore the association of
      monocyte subsets and prognosis in patients with ambulatory heart failure (HF).
      Monocyte subsets were classified as classical (CD14++/CD16-), intermediate
      (CD14++/CD16+), or non-classical (CD14+/CD16++). Percentage distribution and
      absolute cell count were assessed in each subset, and multivariable Cox
      regression analyses were performed with all-cause death, HF-related
      hospitalization, and the composite end-point of both as dependent variables. 400
      patients were consecutively included (72.8% male, age 69.4+/-12.2 years, 45.5%
      from ischemic aetiology, left ventricle ejection fraction (LVEF) 41.6% +/-14.5,
      New York Heart Association (NYHA) class II 62.8% and III 30.8%). During a mean
      follow-up of 2.6+/-0.9 years, 107 patients died, 99 had a HF-related
      hospitalization and 160 suffered the composite end-point of all-cause death or HF
      related hospitalization. Monocyte subsets assessed in percentages were not
      independently associated to any of the end-points. When considering number of
      cells/MUL, intermediate subset was independently associated with an increase of
      all-cause death (HR 1.25 [95% CI 1,02-1.52], p = 0.03), and the composite end
      point HR 1.20 [95% CI 1,03-1.40], p = 0.02). The presented findings show that
      absolute cell count of monocyte subsets was preferred over monocyte percentage
      for prognosis stratification for outpatients with HF. The intermediate monocyte
      subset provides information on increased risk of all-cause death and the
      composite end-point.

PMID- 30240451
TI  - Bio-inspired visual self-localization in real world scenarios using Slow Feature
      Analysis.
AB  - We present a biologically motivated model for visual self-localization which
      extracts a spatial representation of the environment directly from high
      dimensional image data by employing a single unsupervised learning rule. The
      resulting representation encodes the position of the camera as slowly varying
      features while being invariant to its orientation resembling place cells in a
      rodent's hippocampus. Using an omnidirectional mirror allows to manipulate the
      image statistics by adding simulated rotational movement for improved orientation
      invariance. We apply the model in indoor and outdoor experiments and, for the
      first time, compare its performance against two state of the art visual SLAM
      methods. Results of the experiments show that the proposed straightforward model
      enables a precise self-localization with accuracies in the range of 13-33cm
      demonstrating its competitiveness to the established SLAM methods in the tested
      scenarios.

PMID- 30240452
TI  - Apilimod, a candidate anticancer therapeutic, arrests not only PtdIns(3,5)P2 but
      also PtdIns5P synthesis by PIKfyve and induces bafilomycin A1-reversible aberrant
      endomembrane dilation.
AB  - PIKfyve, an evolutionarily conserved kinase synthesizing PtdIns5P and
      PtdIns(3,5)P2, is crucial for mammalian cell proliferation and viability.
      Accordingly, PIKfyve inhibitors are now in clinical trials as anti-cancer drugs.
      Among those, apilimod is the most promising, yet its potency to inhibit PIKfyve
      and affect endomembrane homeostasis is only partially characterized. We
      demonstrate here for the first time that apilimod powerfully inhibited in vitro
      synthesis of PtdIns5P along with that of PtdIns(3,5)P2. HPLC-based resolution of
      intracellular phosphoinositides (PIs) revealed that apilimod triggered a marked
      reduction of both lipids in the context of intact cells. Notably, there was also
      a profound rise in PtdIns3P resulting from arrested PtdIns3P consumption for
      PtdIns(3,5)P2 synthesis. As typical for PIKfyve inhibition and the concomitant
      PtdIns(3,5)P2 reduction, apilimod induced the appearance of dilated endomembrane
      structures in the form of large translucent cytoplasmic vacuoles. Remarkably,
      bafilomycin A1 (BafA1) fully reversed the aberrant cell phenotype back to normal
      and completely precluded the appearance of cytoplasmic vacuoles when added prior
      to apilimod. Inspection of the PI profiles ruled out restoration of the reduced
      PtdIns(3,5)P2 pool as a molecular mechanism underlying BafA1 rescue. Rather, we
      found that BafA1 markedly attenuated the PtdIns3P elevation under PIKfyve
      inhibition. This was accompanied by profoundly decreased endosomal recruitment of
      fusogenic EEA1. Together, our data demonstrate that apilimod inhibits not only
      PtdIns(3,5)P2 but also PtdIns5P synthesis and that the cytoplasmic vacuolization
      triggered by the inhibitor is precluded or reversed by BafA1 through a mechanism
      associated, in part, with reduction in both PtdIns3P levels and EEA1 membrane
      recruitment.

PMID- 30240453
TI  - Binaural localization of musical pitch using interaural time differences in
      congenital amusia.
AB  - Naturally occurring sounds are routinely periodic. The ability to phase-lock to
      such periodicity facilitates pitch perception and interaural time differences
      (ITDs) determination in binaural localization. We examined whether deficient
      pitch processing in individuals with congenital amusia (tone deafness) is
      accompanied by impaired ability to lateralize musical pitch at auditory periphery
      and memorize the location of pitch at the working memory level. If common
      mechanisms subserve processing of temporal-fine-structure based pitch and ITDs,
      then deficient processing of one feature should impair performance on the other.
      Thus, we measured ITD discrimination thresholds using an adaptive-tracking
      procedure for lateralizing musical tone pairs separated by different semitone
      intervals. Amusic individuals exhibited normal ITD thresholds comparable to those
      of matched controls, which were not affected by concurrent pitch changes. For
      working memory tasks, the amusic group performed significantly worse than matched
      controls in probed pitch recall, irrespective of the complexity level of
      concurrent variations along the ITD dimension of the melodic sequence.
      Interestingly, despite normal peripheral ITD thresholds, amusic individuals
      performed worse than controls in recalling probed locations of tones within a
      sequence of musical notes originating from different ITD-simulated locations.
      Findings suggest that individuals with congenital amusia are unimpaired in
      temporal fine-structure encoding to determine the location of musical pitch based
      on binaural ITD information at the auditory periphery. However, working memory
      for a sequence of sounds' ITD-dependent spatial location is here shown to be
      impaired and dissociated from the pitch feature of sounds at the working memory
      level.

PMID- 30240454
TI  - Exogenous glycine inhibits root elongation and reduces nitrate-N uptake in pak
      choi (Brassica campestris ssp. Chinensis L.).
AB  - Nitrogen (N) supply, including NO3--N and organic N in the form of amino acids
      can influence the morphological attributes of plants. For example, amino acids
      contribute to plant nutrition; however, the effects of exogenous amino acids on
      NO3--N uptake and root morphology have received little attention. In this study,
      we evaluated the effects of exogenous glycine (Gly) on root growth and NO3--N
      uptake in pak choi (Brassica campestris ssp. Chinensis L.). Addition of Gly to
      NO3--N agar medium or hydroponic solution significantly decreased pak choi
      seedling root length; these effects of Gly on root morphology were not attributed
      to the proportion of N supply derived from Gly. When pak choi seedlings were
      exposed to mixtures of Gly and NO3--N in hydroponic culture, Gly significantly
      reduced 15NO3--N uptake but significantly increased the number of root tips per
      unit root length, root activity and 15NO3--N uptake rate per unit root length. In
      addition, 15N-Gly was taken up into the plants. In contrast to absorbed NO3--N,
      which was mostly transported to the shoots, a larger proportion of absorbed Gly
      was retained in the roots. Exogenous Gly enhanced root 1-aminocyclopropane-1
      carboxylic acid synthase (ACS) and oxidase (ACO) activities and ethylene
      production. The ethylene antagonists aminoethoxyvinylglycine (0.5 MUM AVG) and
      silver nitrate (10 MUM AgNO3) partly reversed Gly-induced inhibition of primary
      root elongation on agar plates and increased the NO3--N uptake rate under
      hydroponic conditions, indicating exogenous Gly exerts these effects at least
      partly by enhancing ethylene production in roots. These findings suggest Gly
      substantially affects root morphology and N uptake and provide new information on
      the specific responses elicited by organic N sources.

PMID- 30240455
TI  - Correction: Modelling the effects of quadrivalent Human Papillomavirus (HPV)
      vaccination in Puerto Rico.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184540.].

PMID- 30240457
TI  - Editorial: Why was my manuscript rejected?

PMID- 30240456
TI  - Susceptibility-related differences in the quantity of developmental stages of
      Myxobolus spp. (Myxozoa) in fish blood.
AB  - Here, we investigated the early development of two closely related myxozoan
      parasites, the highly pathogenic Myxobolus cerebralis, the causative agent of the
      whirling disease in salmonids, and Myxobolus pseudodispar, a common, non
      pathogenic parasite of cyprinids. The aim of our study was to examine under in
      vivo laboratory conditions whether fish blood is involved in the intrapiscine
      development of the two parasite species and investigate if there is dissimilarity
      between the parasite infection intensity in blood and if it varies in terms of
      host susceptibility and parasite pathogenicity. Highly susceptible, less
      susceptible and non-susceptible hosts were involved. Blood samples were taken 1
      day, 1 week and 1 month post exposure to M. cerebralis and M. pseudodispar,
      respectively. The prevalence and infection intensity was estimated by parasite
      specific quantitative real-time PCR. Although previous findings assumed that M.
      cerebralis might escape from host immune system by migrating via peripheral
      nerves, our experimental results demonstrated that M. cerebralis is present in
      blood during the early stage of intrapiscine development. For the non-pathogenic
      M. pseudodispar, the highest infection prevalence was found in the original host,
      common roach Rutilus rutilus, whereas the highest infection intensity was
      detected in rudd Scardinius erythrophthalmus, a "dead-end" host of the parasite.
      The presence of M. pseudodispar developmental stages in the blood of both
      susceptible and non-susceptible cyprinids suggests that the susceptibility
      differences remain hidden during the early stage of infection. Our findings
      supply further evidence that host specificity is not determined during the early,
      intrapiscine development involving the vascular system. Furthermore, we found
      remarkable differences in the infection dynamics of the two parasite species
      examined, possibly due to their distinct pathogenicity or variations in adaptive
      capabilities to immune components in host blood.

PMID- 30240458
TI  - Erratum: "Determination of the photon beam attenuation by the BrainLAB imaging
      couch: angular and field size dependence".

PMID- 30240459
TI  - Letter to the Editor.

PMID- 30240460
TI  - Paraneoplastic colonic ulcers in an immunodepressed patient.

PMID- 30240461
TI  - An exceptional cause of drug-induced colitis: cholestyramine.

PMID- 30240462
TI  - Direct per-oral pancreatoscopy as a diagnostic tool for intraductal papillary
      mucinous neoplasm.

PMID- 30240463
TI  - A blessed endoscopy.

PMID- 30240464
TI  - Clinical predictors of arterial extravasation, rebleeding and mortality following
      angiographic interventions in gastrointestinal bleeding.
AB  - BACKGROUND AND AIMS: The aim of this study was to identify clinical and imaging
      predictors of arterial extravasation, post embolization rebleeding and 30-day
      mortality in gastrointestinal (GI) bleeding. METHOD: This retrospective study
      included 114 patients who underwent angiography for upper or lower GI bleeding.
      Multivariate logistic regression was used to identify clinical and imaging
      predictors. RESULTS: Angiography demonstrated arterial extravasation in 22
      patients (19%) and embolization was performed in 48 (42%) patients including
      prophylactic embolization in 26 (56%). Fall in hemoglobin level from baseline was
      an independent predictor of arterial extravasation with 65% increased odds for
      every unit drop (OR 1.65, 95%CI 1.13-2.40, p=0.01). Age <60 years was a negative
      predictor of rebleed within 30-days (OR 0.94, 95%CI 0.89-1.00, p=0.04). Patients
      with a history of malignancy were more likely to rebleed (OR 4.4, 95%CI 1.06
      18.36, p=0.04). Hemodynamic instability prior to angiography (OR 13.22, 95%CI
      1.65-106.07, p=0.02), history of malignancy (OR 1.36, 95%CI 1.49-10.49, p=0.01),
      number of units of platelets transfused (OR 1.42, 95%CI 1.02-1.97, p=0.04) and
      rebleed after angiography (OR 46.8, 95%CI 4.80-456.14, p<0.01) were predictors of
      30-day mortality. Prophylactic embolization was not a predictor of rebleed or 30
      day mortality. CONCLUSIONS: This paper identified important clinical predictors
      of arterial extravasation, rebleed and 30-day mortality in GI bleedings, which
      will assist in patient selection and help to improve the overall angiographic
      management of GI bleeding.

PMID- 30240465
TI  - Flexible endoscopic treatment for Zenker's diverticulum - experience on 31
      patients.
AB  - BACKGROUND AND AIMS: The aim of this study is to present the experience of our
      center over the last 8 years in a series of patients with Zenker's diverticulum
      (ZD), treated using an endoscopic, minimally invasive procedure. METHODS: We
      retrospectively included 31 patients with a previously established diagnosis of
      ZD based on endoscopic and oral contrast examinations. Patients' age,
      comorbidities, size of the diverticulum or previous endoscopic treatment were not
      considered exclusion criteria. A soft, flexible diverticuloscope to expose the
      septum and a dual knife for "cutting" the diverticular septum were used. We
      analyzed the short term efficacy based on symptomatic relief and occurrence of
      side effects, and long term efficiency at 6 and 12 months by clinical assessment,
      upper gastrointestinal endoscopy and oral contrast media passage. RESULTS:
      Patients had a mean age of 67 years (range 42-86); 55% of them were male. All
      patients reported symptom relief after the procedure. A decrease of more than 70%
      from the initial size of the diverticulum was noted. There were 3 cases (9.67%)
      of intraprocedural hemorrhage, endoscopically managed. No serious post-procedural
      complications and no mortality were reported. The mean procedural time was 21.87
      minutes (range 15-25 minutes). Average hospitalization was 2.5 days. Five
      patients developed recurrence and needed a second session of endoscopic treatment
      for achieving complete myotomy. CONCLUSIONS: Endoscopic management for ZD was
      efficient and safe in our series of patients. A short hospitalization period was
      required.

PMID- 30240466
TI  - Low yield for routine laboratory checks in follow-up of coeliac disease.
AB  - AIM: To evaluate the yield of routine laboratory tests and Dual Energy X-ray
      Absorptiometry (DEXA) scans in coeliac disease. METHODS: A retrospective analysis
      of medical files of all followed-up patients with coeliac disease attending
      Rijnstate Hospital in 2016 was conducted with respect to blood tests of
      hemoglobin, vitamin B12, folate acid, iron status, calcium, vitamin D, glucose,
      thyroid function, DEXA-scans and related symptoms or signs of abnormalities. All
      patients had positive coeliac serology and/or biopsy-proven coeliac disease and
      attended regular visits after diagnosis. The chi-square test for trend was used
      for statistical analysis: a two-tailed probability of p < 0.05 was considered
      significant. RESULTS: We analyzed 250 patients with a median follow-up of 7.8 (1
      22) years. At diagnosis, we found anemia in 24.4%, iron deficiency in 38%, folic
      acid deficiency in 22.6% and vitamin B12 deficiency in 15.9%. All deficiencies
      recovered within 1-2 years with or without supplements. Deficiencies or
      autoimmune diseases occurred in 50 patients (37 possibly coeliac-related) during
      follow-up. Twelve cases of coeliac-related deficiencies or autoimmune diseases
      occurred in patients with normal values at diagnosis of whom 10 were asymptomatic
      (incidence 10/1000 patient years). Osteoporosis and osteopenia were present in
      23.3% and 35% at diagnosis. In most patients bone mineral density (BMD) improved
      or stabilized during follow up (p < 0.05), 8% deteriorated. CONCLUSIONS: The
      incidence of asymptomatic coeliac-related deficiencies or autoimmune diseases is
      low in patients with normal values at diagnosis. Therefore, routine laboratory
      screening is not necessary in this group: attending regular follow-up visits
      should be sufficient. DEXA scans are recommended.

PMID- 30240467
TI  - Serum cytokines profile in treated celiac disease compared with non-celiac gluten
      sensitivity and control: a marker for differentiation.
AB  - BACKGROUND AND AIMS: There is increasing evidence regarding elevated serum levels
      of inflammatory cytokines in patients with celiac disease (CD), but little is
      known about their levels in patients with non-celiac gluten sensitivity (NCGS).
      The aim of this study was to evaluate the serum levels of inflammatory cytokines
      in Iranian patients with CD and NCGS and to compare them with those of healthy
      individuals. METHODS: A total of 110 treated CD, 15 with NCGS, and 46 healthy
      subjects were enrolled during 2016. Serum levels of IL-1, IL-6, IL-8, IL-15 and
      IFN-gamma were measured using ELISA, and compared between groups. The correlation
      of the severity of mucosal damage and clinical symptoms with serum levels of
      cytokines was also assessed. RESULTS: The mean serum levels of IFN-gamma (p =
      0.04) and IL-6 (p = 0.007) were significantly different between the patients in
      the CD and control groups, and IL-8 was significantly higher in the CD group
      compared with patients in the NCGS group (p = 0.04). Statistically significant
      correlations were observed between the serum levels of IFN-gamma and abortion (p
      = 0.01), IL-1 and weight loss (p = 0.043) and infertility (p = 0.0001) in CD
      patients, and between IFN-gamma and abortion (p = 0.01) and infertility (p =
      0.01) in the NCGS patients. Moreover, no significant relationship was observed
      between the severity of mucosal damage and the serum level of the studied
      cytokines. CONCLUSIONS: Inflammatory cytokines are implicated in the pathogenesis
      of CD, and their serum levels might help to identify a diagnostic marker to
      differentiate CD from NCGS. However, further studies with a larger sample size
      are recommended.

PMID- 30240468
TI  - A differential host response to viral infection defines a subset of earlier-onset
      diverticulitis patients.
AB  - BACKGROUND AND AIMS: Diverticulitis is the chronic inflammation of diverticula.
      Whether the pathophysiology of earlier-onset patients differs from later-onset
      patients is unknown. We profiled the colonic transcriptomes of these two patient
      populations to gain insight into the molecular underpinnings of diverticulitis.
      METHODS: We conducted deep RNA sequencing (RNA-seq) on colonic segments
      surgically resected from earlier-onset (<42 years old, n=13) and later-onset (>65
      years old, n=13) diverticulitis patients. We used bioinformatic approaches to
      cluster the patients based on the relationship of differentially expressed genes
      and to inform on the molecular pathways that segregated the clusters. RESULTS:
      Principal component analysis identified three patient clusters; diverticulitis
      later-onset (DVT-LO), diverticulitis mixed-onset (DVT-MO), and diverticulitis
      earlier-onset (DVT-EO). The patients comprising DVT-EO, which was the majority of
      earlier-onset patients, displayed increased expression of anti-viral response
      genes. This finding was confirmed using an independent weighted co-expression
      network analysis (WGCNA) of differentially expressed genes. CONCLUSIONS: We found
      that the majority of patients with earlier-onset disease contained elevated
      expression of host genes involved in the anti-viral response. Thus,
      susceptibility to a viral pathogen may offer one explanation why some individuals
      develop diverticulitis at an earlier age.

PMID- 30240469
TI  - Predictors of outcome in cognitive and behavioural interventions for irritable
      bowel syndrome. A meta-analysis.
AB  - BACKGROUND AND AIMS: Cognitive behavioural therapy (CBT) has small to medium
      effects in alleviating emotional distress and psychosomatic symptoms in irritable
      bowel syndrome (IBS). However, the mechanism through which CBT exerts its effects
      is less studied. Mediation analysis examines the extent to which intermediate
      variables explain the effect of the intervention on outcomes. The meta-analysis
      aims to identify and assess the impact of CBT mediators identified in previous
      research on IBS. METHODS: An extensive search of studies investigating the
      effects of CBT for IBS published before January 2018 was conducted. A total of
      699 studies were identified through database search and 6 studies including data
      from 638 patients were analysed. The selected studies had to clearly define the
      CBT intervention, include IBS patients, report sufficient data to allow
      calculation of effect sizes and provide a clear mediation analysis of one or
      several variables on the outcome. RESULTS: The total effect of CBT was
      significant for both categories of outcomes (i.e. IBS symptom severity and
      psychosocial distress), with a low-to-moderate effect on psychosocial distress
      (r=0.222) and a medium-to-large effect on IBS symptom severity (r=0.413). In
      fact, the total effect of CBT on IBS symptom severity is significantly higher
      than the total effect on psychosocial distress Q(1)= 5.06, p= 0.024. Both
      behaviours and emotions (r=0.158) as well as cognitions (r=0.141) generated
      significant mediated effects on psychosocial distress, with no significant
      differences between them (Q(1)= 0.05, p=0.825). Behaviours and emotions mediated
      71.1% of the total effect of CBT on psychosocial distress and cognitions mediated
      63.5% of the total effect. CONCLUSION: Although significant for both outcomes,
      the statistical analysis revealed CBT interventions have a greater effect on
      alleviating IBS symptoms severity rather than on reducing psychological distress.
      Of the mediators investigated, behaviours, emotions and cognitions seem to have a
      small to moderating effect in reducing IBS symptom and psychological distress.

PMID- 30240470
TI  - Genetic Variants in nicotinamide-N-methyltransferase (NNMT) gene are related to
      the stage of non-alcoholic fatty liver disease diagnosed by controlled
      attenuation parameter (CAP)-fibroscan.
AB  - BACKGROUND AND AIMS: Various genetic polymorphisms play a key-role in the
      pathogenesis of NAFLD and progression to NASH with fibrosis to cirrhosis. We
      aimed to study the association between single-nucleotide polymorphisms (SNPs) in
      NNMT gene, namely rs694539 and the development of different stages of NAFLD
      diagnosed by controlled attenuation parameter (CAP) of FibroScan Echosens(r).
      METHODS: Transient elastography (FibroScan(r)) with controlled attenuation
      parameter (CAP) measurement was performed in 81 NAFLD patients (35 of them with
      liver biopsy) and 80 non-NAFLD controls. The accuracy of CAP and FibroScan for
      the detection and quantification of hepatic steatosis/fibrosis, respectively, was
      assessed based on liver biopsy aspect. Genetic variants of NNMT gene rs694539
      were analyzed using a polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). RESULTS: According to BMI (kg/m2), among the patients,
      17 (21%) were overweight, 56 (69.1%) obese, and 8 (9.9%) morbidly obese. CAP and
      FibroScan diagnosed steatosis/fibrosis correlated significantly with liver
      biopsy. There was a significant association between polymorphisms of rs694539
      NNMT gene and NAFLD presence and stages. The mutant type (AA-genotype) was found
      in 33% NAFLD patients versus 1.2% controls (P<0.001), whereas the wild type (GG
      genotype) was present in 21% versus 63.8% controls (P<0.001). Moreover, the AA
      genotype significantly correlated with the steatosis degree by CAP but not the
      fibrosis degree by FibroScan. Multivariate regression analysis of all the
      independent risk factors showed non-significant correlations with the degree of
      steatosis on CAP. However, by using a stepwise approach, waist circumference
      showed significance as an independent predictor of NAFLD. CONCLUSIONS:
      Polymorphisms in rs694539-NNMT gene (mutant AA-genotype) could be a genetic risk
      factor for developing NAFLD and NASH (indicating susceptibility for progression
      and complications). Individuals with wild type (GG-genotype) are at less risk of
      NAFLD development. CAP and FibroScan efficiently diagnosed steatosis and
      fibrosis.

PMID- 30240471
TI  - Effect of S-adenosyl-L-methionine on liver biochemistry and quality of life in
      patients with primary biliary cholangitis treated with ursodeoxycholic acid. A
      prospective, open label pilot study.
AB  - BACKGROUND AND AIMS: Chronic liver disease induces an acquired deficiency of S
      adenosyl-L-methionine (SAMe) leading to impairment of detoxifying processes in
      the liver. Ursodeoxycholic acid (UDCA) represents the standard treatment in
      primary biliary cholangitis (PBC). As both compounds exert their hepatoprotective
      effects by different mechanisms, it is conceivable that when used together their
      effect might be additive. The aim of this study was to analyse the effect of SAMe
      supplementation on liver biochemistry and health-related quality of life (HRQoL)
      in patients with PBC, treated with UDCA. METHODS: In this prospective pilot,
      proof of the principle, non-randomized and open label study we enrolled 24
      patients with PBC treated with UDCA for at least 6 months. They had received both
      UDCA in a standard dose of 13-15 mg/kg b.w. and SAMe in the dose of 1200 mg daily
      over a period of 6 months. A group of 24 patients with PBC treated with UDCA
      served as control for liver biochemistry (Study registered on the platform
      ClinicalTrials.gov under ID: NCT02557360). RESULTS: We observed a significant
      decrease of ALP, GGT and total cholesterol in non-cirrhotic patients treated with
      SAMe. There was also a significant improvement of fatigue and pruritus in PBC-40
      questionnaire and amelioration of anxiety in STAI 2 questionnaire in the SAMe
      group. Treatment with SAMe neither increased sulfation capacity of the liver nor
      had an effect on fibroblast growth factor-19 serum levels. CONCLUSIONS: Our pilot
      study demonstrates a positive effect of adding SAMe to UDCA in non-cirrhotic
      patients with PBC.

PMID- 30240473
TI  - Mesalazine to treat symptomatic uncomplicated diverticular disease and to prevent
      acute diverticulitis occurrence. A systematic review with meta-analysis of
      randomized, placebo-controlled trials.
AB  - BACKGROUND AND AIMS: Symptomatic Uncomplicated Diverticular disease (SUDD)
      affects about 25% of patients harboring colonic diverticula. We assessed the
      effectiveness of mesalazine in improving symptoms (namely abdominal pain, primary
      outcome) and in preventing diverticulitis occurrence (secondary outcome) in
      patients with SUDD. METHODS: Pertinent studies were selected from the Medline and
      the Cochrane Central Register of Controlled Trials. Only randomized clinical
      trials (RCTs) (irrespective of language, blinding, or publication status), which
      compared mesalazine, irrespective of the dosage assumption, with placebo in SUDD
      were evaluated. RESULTS: Four RCTs enrolled 379 patients, 197 treated with
      mesalazine and 182 with placebo. Two studies provided data on symptom relief
      according to definition: it was achieved in 97/121 (80%) patients in the
      mesalazine group and in 81/129 (62.7%) patients in the placebo group (OR 0.43;
      95% CI 0.24-0.75; p=0.003 in favour of the mesalazine group). Two studies
      provided information regarding occurrence of diverticulitis during follow-up. It
      occurred in 23/119 (19.3%) patients in the mesalazine group and in 34/102 (33.3%)
      patients in the placebo group (OR 0.35; 95% CI 0.17-0.70; p=0.003 in favour of
      the mesalazine group). CONCLUSIONS: Treatment with mesalazine seems to be
      effective in achieving symptom relief and in the primary prevention of
      diverticulitis in patients with SUDD.

PMID- 30240472
TI  - Impact of direct acting antiviral (DAA) treatment on glucose metabolism and
      reduction of pre-diabetes in patients with chronic hepatitis C.
AB  - BACKGROUND AND AIM: With the development of direct acting antiviral agents (DAA)
      chronic hepatitis C virus (HCV) infection has become curable in most patients.
      Since HCV infection is known to have direct and/or indirect effects on glucose
      metabolism, successful HCV treatment may have an impact in reducing glucose
      level, pre-diabetes, the need of treatment for diabetes, and ultimately diabetes
      associated morbidity. We investigated the association of DAA treatment and
      glucose metabolism in the context of development or resolution of hepatic
      fibrosis in a large cohort of HCV- infected patients. METHODS: In this
      retrospective single-center observational study, we investigated 281 patients
      receiving all-oral DAA therapy for fasting plasma glucose, HbA1c, liver enzymes
      and general clinical chemistry, measured during a 52-week follow-up. In addition,
      elastography, FIB-4- and APRI-calculation were used to assess hepatic fibrosis
      non-invasively. RESULTS: Successful elimination of HCV through DAA treatment was
      associated with a significant drop in fasting glucose level and a reduced rate of
      impaired fasting plasma glucose (FPG). Interestingly, this metabolic change was
      BMI-independent. In addition, long-term glucose levels also decreased after
      successful DAA treatment. A significant APRI-score reduction was associated with
      a persistent improvement of FPG. However, DAA did not have an impact on glucose
      metabolism in patients suffering from liver cirrhosis. CONCLUSION: This study
      highlights the beneficial impact of successful HCV therapy on glucose metabolism
      and identifies patients with liver cirrhosis as a collective in need of
      intensified surveillance with regard to diabetes progression despite HCV
      eradication.

PMID- 30240474
TI  - Fecal calprotectin in assessing inflammatory bowel disease endoscopic activity: a
      diagnostic accuracy meta-analysis.
AB  - BACKGROUND AND AIM: Fecal calprotectin (FC) has been suggested as a sensitive
      biomarker of inflammatory bowel disease (IBD). However, its usefulness in
      assessing IBD activity needs to be more precisely defined. In this meta-analysis
      we aimed to determine the diagnostic performance of FC in assessing IBD
      endoscopic activity in adults. METHODS: We searched the databases PubMed/Medline
      and EMBASE, and studies which examined IBD endoscopic activity in association to
      FC were identified. From each study pooled data and consequently pooled
      sensitivity, specificity, likelihood ratios (LR), diagnostic odds ratios (DORs)
      and areas under the curve (AUCs) were calculated, using suitable meta-analysis
      software. We analyzed extracted data using fixed or random effects models, as
      appropriate, depending on the presence of significant heterogeneity. RESULTS: We
      included 49 sets of data from 25 eligible for meta-analysis studies, with 298
      controls and 2,822 IBD patients. Fecal calprotectin in IBD (Crohn's disease, CD
      and ulcerative colitis, UC) showed a pooled sensitivity of 85%, specificity of
      75%, DOR of 16.3 and AUC of 0.88, in diagnosing active disease. The sub-group
      analysis revealed that FC performed better in UC than in CD (pooled sensitivity
      87.3% vs 82.4%, specificity 77.1% vs 72.1% and AUC 0.91 vs 0.84). Examining the
      optimum FC cut-off levels, the best sensitivity (90.6%) was achieved at 50 MUg/g,
      whereas the best specificity (78.2%) was found at levels >100 MUg/g. CONCLUSIONS:
      This meta-analysis showed that in adults, FC is a reliable laboratory test for
      assessing endoscopic activity in IBD. Its performance is better in UC than CD.

PMID- 30240475
TI  - Clinical application of dietary therapies in irritable bowel syndrome.
AB  - BACKGROUND AND AIMS: Diet appears to play a pivotal role in symptom generation in
      Irritable Bowel Syndrome (IBS). First line dietary therapy for IBS has focused on
      advice concerning healthy eating and lifestyle management. Research recently has
      focused on the role of a diet low in fermentable oligo-, di-, and mono
      saccharides and polyols (FODMAPs), gluten free (GFD) and wheat free (WFD) diets
      for the relief of symptoms in IBS. METHODS: A round table discussion with
      gastroenterologists and dietitians with a specialist interest in dietary
      therapies in IBS was held in Sheffield, United Kingdom in May 2017. Existing
      literature was reviewed. PubMed and EMBASE were searched with the MeSH terms
      irritable bowel syndrome/diet/diet therapy/gluten/low FODMAP in different
      combinations to identify relevant articles. A consensus on the application of
      these dietary therapies into day-to-day practice was developed. RESULTS: Fourteen
      randomized trials in IBS evaluating the low FODMAP diet (n studies = 9), GFD (n =
      4) and WFD (n = 1) were included in this review. The total number of patients
      recruited from randomized trials reviewed was: n=580 low FODMAP diet (female,
      n=430), n=203 GFD (female, n=139), n=276 WFD (female, n=215). There was no
      significant difference in the gender of patients recruited for both the low
      FODMAP and GFD randomized studies (p=0.12). The response rate in the literature
      to a low FODMAP diet ranged between 50-76%, and to GFD ranged between 34-71%.
      Percentage of IBS patients identified as wheat sensitive was reported as 30% in
      the literature. CONCLUSION: There are no head-to-head trials to date utilizing
      the low FODMAP diet, GFD and WFD for dietary treatment of IBS and still a number
      of concerns for diets, including nutritional inadequacy and alteration of the gut
      microbiota. The consensus suggests that there is evidence for the use of the low
      FODMAP diet, GFD and WFD as dietary therapies for IBS; the decision-making
      process for using each individual therapy should be directed by a detailed
      history by the dietitian, involving the patient in the process.

PMID- 30240476
TI  - Usefulness of the modified clip-with-line method for endoscopic mucosal treatment
      procedure.
AB  - Endoscopic submucosal dissection (ESD) might be difficult to perform in some
      cases even for experienced endoscopists. Recently, various traction methods have
      been introduced to facilitate ESD procedures, such as clip-with-line (CL),
      external forceps, clip and snare, internal traction, double scope, and magnetic
      anchor. The traction procedure using the CL method enhances the visibility of the
      operation field during ESD. The original CL method is performed as follows: the
      clip with the line (e.g., dental floss) is attached to the edge of the lesion.
      Traction can be produced by pulling the line gently, thus achieving a sufficient
      visualization of the submucosal layer to identify an accurate cutting line.
      Herein, we present a useful modified two-CL method by pulling the appropriate
      normal mucosa to enhance the visibility of the operation field during ESD
      procedure. Thus, the traction methods, including our modified CL technique, might
      reduce the procedure time and complications.

PMID- 30240477
TI  - Mitochondrial neurogastrointestinal encephalomyopathy imitating Crohn's disease:
      a rare cause of malnutrition.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal
      recessive disease caused by a mutation in the TYMP gene encoding thymidine
      phosphorylase. MNGIE causes gastrointestinal and neurological symptoms in
      homozygous individuals and is often misdiagnosed as anorexia nervosa,
      inflammatory bowel disease, or celiac disease. We present the case of a 26-year
      old female with MNGIE, who was initially diagnosed with anorexia nervosa and
      Crohn's disease. The diagnosis of MNGIE was established by biochemical
      confirmation of elevated serum and urine thymidine and deoxyuridine levels after
      multiple examinations and several years of disease progression and ineffective
      treatment. Subsequent molecular genetic testing demonstrated a homozygous TYMP
      gene mutation. MNGIE should be considered in patients with unexplained
      malnutrition, intestinal dysmotility, and atypical neurological symptoms.

PMID- 30240478
TI  - Treatment of refractory mastocytic enterocolitis with budesonide.
AB  - Mast cells (MCs) are being increasingly implicated as a possible contributor to
      symptoms in diarrhea predominant irritable bowel syndrome (IBS). The term
      "mastocytic enterocolitis" was proposed to describe an increase in mucosal MCs in
      patients with chronic diarrhea due to functional gastrointestinal disease (FGID).
      The efficacy of anti-MC mediator therapy (antihistamines and MC stabilizers) has
      been well documented in this setting. Here we describe the treatment with oral
      budesonide of mastocytic enterocolitis refractory to standard anti-MC therapy.

PMID- 30240479
TI  - Whipple's disease: case report and review of the literature.
AB  - Whipple's disease (WD) is known as an infrequent, systemic, chronic infection
      caused by the actinomycete Tropherima whipplei (T. whipplei). The disease is
      frequently characterized by a long prodromal and protean extra-intestinal phase,
      which often causes misdiagnosis and inappropriate treatments. Herein, we describe
      the case a 62-year-old man with a histological diagnosis of WD established when
      oral steroid treatment was started due to rheumatic manifestations, triggering
      intestinal symptoms. Systematic review of the literature was performed to include
      studies where WD was eventually diagnosed on duodenal biopsies. Three patients'
      subgroups were identified according to the clinical presentation.

PMID- 30240480
TI  - Sensitive response to ingestion of lipids in dyspepsia.

PMID- 30240481
TI  - Reply.

PMID- 30240482
TI  - Capitol Matters: TMA Weighs in on Medicaid MCO's, Telemedicine Before Texas
      Legislature.

PMID- 30240483
TI  - Rural Doc Hopes to Build Ties With Big Cities.
AB  - Jacksonville OB-Gyn hopes rural docs and big centers can build collegiality.

PMID- 30240484
TI  - Talk to Patients About: Varicella.
AB  - The varicella-zoster virus does double-duty: It can cause chickenpox when you're
      young and reactivate later in life as a painful, blistery rash called shingles.
      Well, there's a vaccine for each disease.

PMID- 30240485
TI  - Vaccines on a Shelf: Vaccines in Development Often Sit Around Untested.
AB  - Vaccines in development for diseases in Texas and beyond often sit around
      untested.

PMID- 30240486
TI  - The Results Are In: Physicians Finally See How They Fared in First Year of MIPS.
AB  - Physicians finally see how they fared in the first year of Medicare's "MIPS"
      quality payment program.

PMID- 30240487
TI  - What To Do When Employees Steal: Medical Practices Are a Ripe Target for
      Embezzlement.
AB  - Medical practices are a ripe target for embezzlement.

PMID- 30240488
TI  - Financial Squeeze: Low Medicaid pay has Dallas clinics turning to midlevels to
      cut costs.
AB  - Low Medicaid pay forces some Children's Health Pediatric Group clinics in Dallas
      to close, others turn to midlevels to cut costs, raising quality concerns.

PMID- 30240489
TI  - Coming of Age: Celebrating 15 Years of Texas Tort Reform.
AB  - After 15 years, the power of Texas' tort reforms shows up in both the numbers and
      the attitudes of physicians across the state, with less pressure to practice
      defensively, and more specialists filling rural voids.

PMID- 30240490
TI  - New insights on relaxant effects of (-)-borneol monoterpene in rat aortic rings.
AB  - The monoterpene alcohol (-)-borneol has many biological effects such as sedative,
      anti-inflammatory, analgesic, anti-nociceptive, antithrombotic and vasorelaxant
      effects. Our objective in this study was to investigate the mechanism of action
      of (-)-borneol and determine its vasorelaxant effect. (-)-Borneol was tested on
      isolated aortic rings contracted with PE (10-6  m). This study was performed in
      the absence or in the presence of endothelium, L-NAME (100 MUm), indomethacin (10
      MUm), TEA (1 and 10 mm), 4-AP (1 mm) or glibenclamide (1 mm) to assess the
      participation of EDRF, nitric oxide, prostanoids and potassium channels on the
      relaxing effect of (-)-borneol. In this work, (-)-borneol induced a relaxant
      effect in aortic rings, with and without endothelium, in a concentration
      dependent manner. The pharmacological characterization obtained using L-NAME,
      indomethacin, TEA, 4-AP and glibenclamide demonstrates that the effect of (-)
      borneol was modified in the presence of L-NAME, indomethacin and glibenclamide
      showing that these signal transduction pathways are involved in the relaxing
      effect of the monoterpene. (-)-Borneol has a vasorelaxant effect that depends on
      the presence of vascular endothelium, with the participation of nitric oxide and
      prostanoids. Also, (-)-borneol displayed a direct action on the vascular smooth
      muscle, greatly dependent on KATP channels.

PMID- 30240491
TI  - Hepatic artery stenosis after liver transplant: Donation after cardiac death
      donor vs donation after brain death donor grafts.
AB  - BACKGROUND: Hepatic artery stenosis (HAS) after liver transplant (LT) is a source
      of significant morbidity. Some reports have suggested higher arterial
      complications in patients who receive donation after cardiac death (DCD) livers.
      METHODS: A total of 2860 consecutive LT were reviewed from a prospectively
      collected database. All angiograms performed in LT recipients were reviewed and
      primary patency rates determined by need for further intervention or graft loss
      due to HAT. RESULTS: Hepatic artery stenosis was seen in 4.6% of DCD and donation
      after brain death (DBD) recipients. Recipient male gender, age at transplant,
      complex donor hepatic artery anatomy, and prolonged operative time were all
      associated with HAS, but not DCD status. While HAS in recipients of DCD grafts
      required more stents (1.7% vs 0.6%, P = 0.04) and had worse primary patency rates
      (logrank, P = 0.02), outcomes as defined by HAT, patient and graft survival were
      not significantly different between the recipients of DCD or DBD grafts.
      CONCLUSION: We observed no significant difference in the incidence of hepatic
      artery complications, patient survival, or graft survival in recipients of DCD or
      DBD grafts. However, HAS in DCD recipients had worse primary patency and a higher
      need for stent placement.

PMID- 30240492
TI  - Neural substrates of word category information as the basis of syntactic
      processing.
AB  - The ability to use word category information (WCI) for syntactic structure
      building has been hypothesized to be the essence of human language faculty. The
      neural substrate of the ability of using the WCI for the complex syntactic
      hierarchical structure processing, however, is yet unknown. Therefore, we
      directly conducted an fMRI experiment by using a pseudo-Chinese artificial
      language with syntactic structures containing a center-embedded relative clause.
      Thirty non-Chinese native (Korean) speakers were randomly divided into two
      groups: one acquired WCI and WCI-based syntactic rules (the WCI group) before the
      scanning session, and the other did not (the non-WCI group). Both groups were
      required to judge the grammaticality of the testing sentences, with critical long
      distance dependencies between two elements (the main verb and the relativizer).
      Behaviorally, the WCI group's accuracy was significantly higher and its reaction
      time was shorter. The scanning results showed that the left superior temporal
      gyrus (STG) and Broca's area were more strongly activated for the WCI group, and
      the dynamic causal modeling analyses revealed a distinct effective connectivity
      pattern for this group. Therefore, the present research, for the first time,
      reveals that the activation of and the functional connectivity between Broca's
      area and the left STG play a critical role in the ability of the rule-based use
      of the WCI which is crucial for complex hierarchical structure building, and
      might be substantially corresponding to the "labeling competence" within the
      linguistic framework.

PMID- 30240493
TI  - Frequency-specific age-related decreased brain network diversity in cognitively
      healthy elderly: A whole-brain data-driven analysis.
AB  - Age-related changes in functional brain network have been well documented.
      However, recent studies have suggested the nonstationary properties of the
      functional connectivity of the brain, and little is known about the changes of
      functional connectivity dynamics during aging. In this study, a two-step singular
      value decomposition was introduced to capture the dynamic patterns of the time
      varying functional connectivity in different frequency intervals, and the whole
      brain and regional brain diversity were quantified by using Shannon entropy. The
      relationships between age and functional connectivity dynamics were investigated
      in a relatively large sample cohort of cognitively healthy elderly (N = 188, ages
      65-80). The results showed an age-related decreased diversity in the whole brain
      as well as in the right inferior frontal gyrus, right amygdala, right
      hippocampus, left parahippocampal, and left inferior parietal gyrus in the
      frequency interval of 0.06-0.12 Hz. In addition, the whole-brain diversity during
      resting state could also reflect the general mental flexibility. This study
      provided the first evidence of frequency-specific age effects on the functional
      connectivity dynamics in cognitively healthy elderly, and may shed new light on
      the dynamic functional connectivity analysis of aging and neurodegenerative
      diseases.

PMID- 30240494
TI  - Cognitive loading via mental arithmetic modulates effects of blink-related
      oscillations on precuneus and ventral attention network regions.
AB  - Blink-related oscillations (BROs) have been linked with environmental monitoring
      processes associated with blinking, with cortical activations in the bilateral
      precuneus. Although BROs have been described under resting and passive fixation
      conditions, little is known about their characteristics under cognitive loading.
      To address this, we investigated BRO effects during both mental arithmetic (MA)
      and passive fixation (PF) tasks using magnetoencephalography (n =20), while
      maintaining the same sensory environment in both tasks. Our results confirmed the
      presence of BRO effects in both MA and PF tasks, with similar characteristics
      including blink-related increase in global field power and blink-related
      activation of the bilateral precuneus. In addition, cognitive loading due to MA
      also modulated BRO effects by decreasing BRO-induced cortical activations in key
      brain regions including the bilateral anterior precuneus. Interestingly, blinking
      during MA-but not PF-activated regions of the ventral attention network (i.e.,
      right supramarginal gyrus and inferior frontal gyrus), suggesting possible
      recruitment of these areas for blink processing under cognitive loading
      conditions. Time-frequency analysis revealed a consistent pattern of BRO-related
      effects in the precuneus in both tasks, but with task-related functional
      segregation within the anterior and posterior subregions. Based on these
      findings, we postulate a potential neurocognitive mechanism for blink processing
      in the precuneus. This study is the first investigation of BRO effects under
      cognitive loading, and our results provide compelling new evidence for the
      important cognitive implications of blink-related processing in the human brain.

PMID- 30240495
TI  - Altered structural and functional brain network overall organization predict
      human intertemporal decision-making.
AB  - Intertemporal decision-making is naturally ubiquitous to us: individuals always
      make a decision with different consequences occurring at different moments. These
      choices are invariably involved in life-changing outcomes regarding marriage,
      education, fertility, long-term well-being, and even public policy. Previous
      studies have clearly uncovered the neurobiological mechanism of the intertemporal
      decision in the schemes of regional location or sub-network. However, it still
      remains unclear how to characterize intertemporal behavior with multimodal whole
      brain network metrics to date. Here, we combined diffusion tensor image and
      resting-state functional connectivity MRI technology, in conjunction with graph
      theoretical analysis, to explore the link between topological properties of
      integrated structural and functional whole-brain networks and intertemporal
      decision-making. Graph-theoretical analysis illustrated that the participants
      with steep discounting rates exhibited the decreased global topological
      organizations including small-world and rich-club regimes in both functional and
      structural connectivity networks, and reflected the dreadful local topological
      dynamics in the modularity of functional connectome. Furthermore, in the cross
      modalities configuration, the same relationship was predominantly observed for
      the coupling of structural-functional connectivity as well. Above topological
      metrics are commonly indicative of the communication pattern of simultaneous
      global and local parallel information processing, and it thus reshapes our
      accounts on intertemporal decision-making from functional regional/sub-network
      scheme to multimodal brain overall organization.

PMID- 30240496
TI  - Design of a Multicompartment Hydrogel that Facilitates Time-Resolved Delivery of
      Combination Therapy and Synergized Killing of Glioblastoma.
AB  - There is significant current interest in identifying new combination therapies
      that synergize to treat disease, and it is becoming increasingly clear that the
      temporal resolution of their administration greatly impacts efficacy. To
      facilitate effective delivery, a multicompartment hydrogel material was developed
      that is composed of spherical vesicles interlaced within a self-assembled peptide
      based network of physically crosslinked fibrils that allows time-resolved
      independent co-delivery of small molecules. This material architecture
      effectively delivers the EGFR kinase inhibitor Erlotinib (ERL) and Doxorubicin
      (DOX, DNA intercalator) in an ERL->DOX sequential manner to synergistically kill
      glioblastoma, the most aggressive form of brain cancer.

PMID- 30240497
TI  - Assessment of the Pig-a, micronucleus, and comet assay endpoints in rats treated
      by acute or repeated dosing protocols with procarbazine hydrochloride and ethyl
      carbamate.
AB  - The utility and sensitivity of the newly developed flow cytometric Pig-a gene
      mutation assay have become a great concern recently. In this study, we have
      examined the feasibility of integrating the Pig-a assay as well as micronucleus
      and Comet endpoints into acute and subchronic general toxicology studies. Male
      Sprague-Dawley rats were treated for 3 or 28 consecutive days by oral gavage with
      procarbazine hydrochloride (PCZ) or ethyl carbamate (EC) up to the maximum
      tolerated dose. The induction of CD59-negative reticulocytes and erythrocytes,
      micronucleated reticulocytes in peripheral blood, micronucleated polychromatic
      erythrocytes in bone marrow, and Comet responses in peripheral blood, liver,
      kidney, and lung were evaluated at one, two, or more timepoints. Both PCZ and EC
      produced positive responses at most analyzed timepoints in all tissue types, both
      with the 3-day and 28-day treatment regimens. Furthermore, comparison of the
      magnitude of the genotoxicity responses indicated that the micronucleus and Comet
      endpoints generally produced greater responses with the higher dose, short-term
      treatments in the 3-day study, while the Pig-a assay responded better to the
      cumulative effects of the lower dose, but repeated subchronic dosing in the 28
      day study. Collectively, these results indicate that integration of several in
      vivo genotoxicity endpoints into a single routine toxicology study is feasible
      and that the Pig-a assay may be particularly suitable for integration into
      subchronic dose studies based on its ability to accumulate the mutations that
      result from repeated treatments. This characteristic may be especially important
      for assaying lower doses of relatively weak genotoxicants. Environ. Mol. Mutagen.
      2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30240499
TI  - The role of diversity in data-driven analysis of multi-subject fMRI data:
      Comparison of approaches based on independence and sparsity using global
      performance metrics.
AB  - Data-driven methods have been widely used in functional magnetic resonance
      imaging (fMRI) data analysis. They extract latent factors, generally, through the
      use of a simple generative model. Independent component analysis (ICA) and
      dictionary learning (DL) are two popular data-driven methods that are based on
      two different forms of diversity-statistical properties of the data-statistical
      independence for ICA and sparsity for DL. Despite their popularity, the
      comparative advantage of emphasizing one property over another in the
      decomposition of fMRI data is not well understood. Such a comparison is made
      harder due to the differences in the modeling assumptions between ICA and DL, as
      well as within different ICA algorithms where each algorithm exploits a different
      form of diversity. In this paper, we propose the use of objective global
      measures, such as time course frequency power ratio, network connection summary,
      and graph theoretical metrics, to gain insight into the role that different types
      of diversity have on the analysis of fMRI data. Four ICA algorithms that account
      for different types of diversity and one DL algorithm are studied. We apply these
      algorithms to real fMRI data collected from patients with schizophrenia and
      healthy controls. Our results suggest that no one particular method has the best
      performance using all metrics, implying that the optimal method will change
      depending on the goal of the analysis. However, we note that in none of the
      scenarios we test the highly popular Infomax provides the best performance,
      demonstrating the cost of exploiting limited form of diversity.

PMID- 30240498
TI  - Commissural communication allows mouse intergeniculate leaflet and ventral
      lateral geniculate neurons to encode interocular differences in irradiance.
AB  - KEY POINTS: Unlike other visual thalamic regions, the intergeniculate leaflet and
      ventral lateral geniculate nucleus (IGL/vLGN) possess extensive reciprocal
      commissural connections, the functions of which are unknown. Using
      electrophysiological approaches, it is shown that commissural projecting IGL/vLGN
      cells are primarily activated by light increments to the contralateral eye while
      cells receiving commissural input typically exhibit antagonistic binocular
      responses. Across antagonistic cells, the nature of the commissural input
      (excitatory or inhibitory) corresponds to the presence of ipsilateral ON or OFF
      visual responses and in both cases antagonistic responses disappear following
      inactivation of the contralateral thalamus. The steady state firing rates of
      antagonistic cells uniquely encode interocular differences in irradiance. There
      is a pivotal role for IGL/vLGN commissural signalling in generating new sensory
      properties that are potentially useful for the proposed contributions of these
      nuclei to visuomotor/vestibular and circadian control. ABSTRACT: The
      intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/vLGN) are
      portions of the visual thalamus implicated in circadian and visuomotor/vestibular
      control. A defining feature of IGL/vLGN organisation is the presence of extensive
      reciprocal commissural connections, the functions of which are at present
      unknown. Here we use a combination of multielectrode recording, electrical
      microstimulation, thalamic inactivation and a range of visual stimuli in mice to
      address this deficit. Our data indicate that, like most IGL/vLGN cells, those
      that project commissurally primarily convey contralateral ON visual signals while
      most IGL/vLGN neurons that receive this input exhibit antagonistic binocular
      responses (i.e. excitatory responses driven by one eye and inhibitory responses
      driven by the other), enabling them to encode interocular differences in
      irradiance. We also confirm that this property derives from commissural input
      since, following inactivation of the contralateral visual thalamus, these cells
      instead display monocular contralateral-driven ON responses. Our data thereby
      reveal a fundamental role for commissural signalling in generating new visual
      response properties at the level of the visual thalamus.

PMID- 30240500
TI  - Reply to "The epidemiology of hepatitis B virus infection in China".

PMID- 30240501
TI  - Interactions between superoxide dismutase and paraoxonase polymorphic variants in
      nonsyndromic cleft lip with or without cleft palate in the Brazilian population.
AB  - During development, oxidative stress is hypothesized to mediate embryotoxicity,
      which may be intensified by exposition to environmental factors and by genetic
      variations in the enzymes involved in protecting cells from these damaging
      effects, including superoxide dismutase (SOD) and paraoxonase (PON). The aim of
      this study was to evaluate the influence of single-nucleotide polymorphisms (SNP)
      in genes associated with the neutralization of oxidative stress (SOD and PON
      family members) in the risk of nonsyndromic oral cleft in the Brazilian
      population. Initially, we tested for association between 28 SNP in SOD1, SOD2,
      SOD3, PON1, PON2, and PON3 among 325 nonsyndromic cleft lip with or without cleft
      palate (NSCL+/-P) case-parent trios. Multiple logistic regression analyses were
      used to explore gene, GxG and GxE, involving factors that induce oxidative stress
      accumulation during pregnancy. Signals still significant after both Bonferroni
      correction and in permutation test were subsequently confirmed in an ancestry
      structured case-control analysis with 722 NSCL+/-P and 866 controls from the same
      population. In the trio sample, transmission disequilibrium test (TDT) (allele
      and haplotype) and GxE analysis showed no significant associations, but multiple
      pairwise GxG interactions involving 10 SNP in PON1, PON2, and PON3 were detected
      and further examined in the case-control sample. The PON1 rs2237583 and PON2
      rs17166879 yielded significant evidence of SNP-SNP interactions after adjustment
      for multiple tests (both Bonferroni correction and 10,000 permutation test). The
      C allele and the CT genotype of PON1 rs2237583 were associated with significant
      protective effects against NSCL+/-P, while rs3917490 showed a significant
      association only in the sample composed of patients displaying high African
      ancestry. Our results reveal associations between rs2237583 and rs3917490 in PON1
      and GxG interactions containing rs2237583 and rs17166879 with the susceptibility
      of NSCL+/-P in the Brazilian population. Furthermore, this study underlines the
      recent tendency of taking into account potential GxG interactions to clarify the
      underlying mechanisms associated with the etiology of this common malformation.

PMID- 30240503
TI  - Reduction in gray matter of cerebellum in schizophrenia and its influence on
      static and dynamic connectivity.
AB  - Pathophysiological and atrophic changes in the cerebellum have been well
      documented in schizophrenia. Reduction of gray matter (GM) in the cerebellum was
      confirmed across cognitive and motor cerebellar modules in schizophrenia. Such
      abnormalities in the cerebellum could potentially have widespread effects on both
      sensorimotor and cognitive symptoms. In this study, we investigated how reduction
      change in the cerebellum affects the static and the dynamic functional
      connectivity (FC) between the cerebellum and cortical/subcortical networks in
      schizophrenia. Reduction of GM in the cerebellum was confirmed across the
      cognitive and motor cerebellar modules in schizophrenic subjects. Results from
      this study demonstrates that the extent of reduction of GM within cerebellum
      correlated with increased static FCs between the cerebellum and the
      cortical/subcortical networks, including frontoparietal network (FPN), and
      thalamus in patients with schizophrenia. Decreased GM in the cerebellum was also
      associated with a declined dynamic FC between the cerebellum and the FPN in
      schizophrenic subjects. The severity of patients' positive symptom was related to
      these structural-functional coupling score of cerebellum. These findings
      identified potential cerebellar driven functional changes associated with
      positive symptom deficits. A post hoc analysis exploring the effect of changed FC
      within cerebellum, confirmed that a significant positive relationship, between
      dynamic FCs of cerebellum-thalamus and intracerebellum existed in patients, but
      not in controls. The reduction of GM within the cerebellum might be associated
      with modulation of cerebellum-thalamus, and contributes to the dysfunctional
      cerebellar-cortical communication in schizophrenia. Our results provide a new
      insight into the role of cerebellum in understanding the pathophysiological of
      schizophrenia.

PMID- 30240502
TI  - matchbox: An open-source tool for patient matching via the Matchmaker Exchange.
AB  - Rare disease investigators constantly face challenges in identifying additional
      cases to build evidence for gene-disease causality. The Matchmaker Exchange (MME)
      addresses this limitation by providing a mechanism for matching patients across
      genomic centers via a federated network. The MME has revolutionized searching for
      additional cases by making it possible to query across institutional boundaries,
      so that what was once a laborious and manual process of contacting researchers is
      now automated and computable. However, while the MME network is beginning to
      scale, the growth of additional nodes is limited by the lack of easy-to-use
      solutions that can be implemented by any rare disease database owner, even one
      without significant software engineering resources. Here, we describe matchbox,
      which is an open-source, platform-independent, portable bridge between any given
      rare disease genomic center and the MME network, which has already led to novel
      gene discoveries. We also describe how matchbox greatly reduces the barrier to
      participation by overcoming challenges for new databases to join the MME.

PMID- 30240504
TI  - Functional plasticity of the dorsomedial prefrontal cortex in depression
      reorganized by electroconvulsive therapy: Validation in two independent samples.
AB  - Previous studies have implied a key role for the prefrontal cortex in the
      antidepressive effect of electroconvulsive therapy (ECT). However, there is still
      ubiquitous inconsistency across these studies, partly due to several confounding
      effects induced by the use of different samples. Studies with independent samples
      are necessary for validations to minimize confounding effects. In the current
      study, resting-state magnetic resonance imaging of 84 participants was collected
      using two scanners and two types of scanning parameters. One sample consisted of
      28 patients and 23 healthy controls, and the other sample consisted of 33
      patients. The local activity (indexed by the amplitude of low-frequency
      fluctuations) and functional connectivity were used to examine functional
      plasticity in the two independent samples before and after ECT. Both samples
      showed increased local activity of the dorsomedial prefrontal cortex (DMPFC) and
      enhanced connectivity of the DMPFC with the posterior cingulate cortex (PCC)
      following ECT. The enhanced connectivity between the DMPFC and PCC was positively
      associated with clinical improvement for both samples. These findings provide
      relatively strong evidence to support the functional plasticity of the
      dorsomedial prefrontal cortex and reorganization by ECT. The functional
      plasticity of the DMPFC-PCC may underlie the antidepressive effect of ECT.

PMID- 30240505
TI  - Substantial impact of seed-feeding fly on seed production of five endangered
      Japanese orchids.

PMID- 30240507
TI  - Cannabis and periodontal harm: How convincing is the association?

PMID- 30240506
TI  - A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides
      reveals adaptive regulation of protective functions during hibernation.
AB  - The small South American marsupial, Dromiciops gliroides, known as the missing
      link between the American and the Australian marsupials, is one of the few South
      American mammals known to hibernate. Expressing both daily torpor and seasonal
      hibernation, this species may provide crucial information about the mechanisms
      and the evolutionary origins of marsupial hibernation. Here, we compared torpid
      and active individuals, applying high-throughput sequencing technologies (RNA
      seq) to profile gene expression in three D. gliroides tissues and determine
      whether hibernation induces tissue-specific differential gene expression. We
      found 566 transcripts that were significantly up-regulated during hibernation
      (369 in brain, 147 in liver and 50 in skeletal muscle) and 339 that were down
      regulated (225 in brain, 79 in liver and 35 in muscle). The proteins encoded by
      these differentially expressed genes orchestrate multiple metabolic changes
      during hibernation, such as inhibition of angiogenesis, prevention of muscle
      disuse atrophy, fuel switch from carbohydrate to lipid metabolism, protection
      against reactive oxygen species and repair of damaged DNA. According to the
      global enrichment analysis, brain cells seem to differentially regulate a complex
      array of biological functions (e.g., cold sensitivity, circadian perception,
      stress response), whereas liver and muscle cells prioritize fuel switch and heat
      production for rewarming. Interestingly, transcripts of thioredoxin-interacting
      protein (TXNIP), a potent antioxidant, were significantly over-expressed during
      torpor in all three tissues. These results suggest that marsupial hibernation is
      a controlled process where selected metabolic pathways show adaptive modulation
      that can help to maintain homeostasis and enhance cytoprotection in the
      hypometabolic state.

PMID- 30240508
TI  - Impact of anticoagulant choice on hospitalized bleeding risk when treating cancer
      associated venous thromboembolism.
AB  - Essentials Bleeding risk by anticoagulant choice for cancer-associated venous
      thrombosis (CA-VTE) is unknown. 26 894 people with CA-VTE were followed for
      bleeding in a claims database in the United States. Hospitalized bleeding risk
      was similar with direct acting oral anticoagulants vs. warfarin. Relative
      hospitalized bleeding risk varied by cancer type and anticoagulant choice.
      SUMMARY: Background Direct acting oral anticoagulants (DOACs) are associated with
      less bleeding than traditional venous thromboembolism (VTE) treatments in the
      general population but are little studied in cancer-associated VTE (CA-VTE).
      Objective To determine whether different anticoagulation strategies for CA-VTE
      have different hospitalized bleeding rates. Patients/Methods We conducted a
      retrospective study of patients with CA-VTE, diagnosed between 2011 and 2015, in
      a large administrative database. Using validated algorithms, we identified 26 894
      CA-VTE patients treated with anticoagulants and followed them for hospitalized
      severe bleeding. Cox models were used to assess bleeding risk, adjusted for age,
      sex, high dimensional propensity score and frailty. Results Over 27 281 person
      years of follow-up (median 0.6 years), 1204 bleeding events occurred, for a
      bleeding rate of 4.4% per patient-year. Bleeding rates varied by cancer type,
      with the highest rate for upper gastrointestinal cancers (8.6%) and the lowest
      for breast cancer (2.9%). In Cox models (hazard ratio [HR]; 95% confidence
      interval [CI]), compared with warfarin, DOACS and low-molecular-weight heparin
      (LMWH) had similar hazards of bleeding (HR, 0.88; 95% CI, 0.69-1.11 and 0.98;
      0.85-1.13). Compared with LMWH, there was no difference in hazard of bleeding
      with DOACs (0.86; 0.66-1.12). There was heterogeneity in bleeding risk with DOACs
      by cancer type, with a higher risk of bleeding in upper gastrointestinal cancers
      and lower risk of bleeding in prostate cancer and hematologic cancers.
      Conclusions In this practice-based sample of CA-VTE patients, DOACs were
      associated with similar bleeding risks to warfarin and LMWH. These findings
      suggest a complex association of bleeding risk with anticoagulant choice in
      cancer patients.

PMID- 30240510
TI  - An integrative approach to investigating bilingual advantages in cognitive
      decline: The Australian Longitudinal Study of Ageing.

PMID- 30240511
TI  - The neurophysiological basis of developmental changes during sequential cognitive
      flexibility between adolescents and adults.
AB  - Cognitive flexibility is a major facet of executive functions and often refers to
      sequential task control; that is, it is very likely that one may re-encounter a
      task that has previously been abandoned to carry out a different task. In the
      context of sequential cognitive flexibility, the "backward inhibition (BI)
      effect" has been studied quite extensively. Here we ask whether there are age
      related differences between adolescents and adults to overcome BI and what system
      neurophysiological mechanisms underlie these modulations. This was examined using
      a system neurophysiological study procedure combining event-related potentials
      data with source localization and EEG signal decomposition methods. We show that
      sequential cognitive flexibility, and the ability overcome backward inhibition,
      is inferior in adolescents compared with adults. Accounting for intra-individual
      variability in the neurophysiological data, this data suggest that two partly
      inter-related processes underlie the differences between adolescents than adults
      to overcome backward inhibition: One process refers to the suppression of the
      inhibitory effect of the n-1 trial on the n-2 trial during perceptual
      categorization of incoming information that is associated with right inferior
      frontal regions. The other process refers to immature response selection and
      conflict monitoring mechanisms associated with regions in the medial frontal
      cortex.

PMID- 30240509
TI  - Mapping adolescent reward anticipation, receipt, and prediction error during the
      monetary incentive delay task.
AB  - The functional neuroanatomy and connectivity of reward processing in adults are
      well documented, with relatively less research on adolescents, a notable gap
      given this developmental period's association with altered reward sensitivity.
      Here, a large sample (n = 1,510) of adolescents performed the monetary incentive
      delay (MID) task during functional magnetic resonance imaging. Probabilistic maps
      identified brain regions that were reliably responsive to reward anticipation and
      receipt, and to prediction errors derived from a computational model.
      Psychophysiological interactions analyses were used to examine functional
      connections throughout reward processing. Bilateral ventral striatum, pallidum,
      insula, thalamus, hippocampus, cingulate cortex, midbrain, motor area, and
      occipital areas were reliably activated during reward anticipation. Bilateral
      ventromedial prefrontal cortex and bilateral thalamus exhibited positive and
      negative activation, respectively, during reward receipt. Bilateral ventral
      striatum was reliably active following prediction errors. Previously, individual
      differences in the personality trait of sensation seeking were shown to be
      related to individual differences in sensitivity to reward outcome. Here, we
      found that sensation seeking scores were negatively correlated with right
      inferior frontal gyrus activity following reward prediction errors estimated
      using a computational model. Psychophysiological interactions demonstrated
      widespread cortical and subcortical connectivity during reward processing,
      including connectivity between reward-related regions with motor areas and the
      salience network. Males had more activation in left putamen, right precuneus, and
      middle temporal gyrus during reward anticipation. In summary, we found that, in
      adolescents, different reward processing stages during the MID task were robustly
      associated with distinctive patterns of activation and of connectivity.

PMID- 30240512
TI  - Applications of mechanistic modelling to clinical and experimental immunology: an
      emerging technology to accelerate immunotherapeutic discovery and development.
AB  - The application of in-silico modelling is beginning to emerge as a key
      methodology to advance our understanding of mechanisms of disease pathophysiology
      and related drug action, and in the design of experimental medicine and clinical
      studies. From this perspective, we will present a non-technical discussion of a
      small number of recent and historical applications of mathematical, statistical
      and computational modelling to clinical and experimental immunology. We focus
      specifically upon mechanistic questions relating to human viral infection, tumour
      growth and metastasis and T cell activation. These exemplar applications
      highlight the potential of this approach to impact upon human immunology informed
      by ever-expanding experimental, clinical and 'omics' data. Despite the capacity
      of mechanistic modelling to accelerate therapeutic discovery and development and
      to de-risk clinical trial design, it is not utilized widely across the field. We
      outline ongoing challenges facing the integration of mechanistic modelling with
      experimental and clinical immunology, and suggest how these may be overcome.
      Advances in key technologies, including multi-scale modelling, machine learning
      and the wealth of 'omics' data sets, coupled with advancements in computational
      capacity, are providing the basis for mechanistic modelling to impact on
      immunotherapeutic discovery and development during the next decade.

PMID- 30240513
TI  - Mating-type factor-specific regulation of the fumagillin/pseurotin secondary
      metabolite supercluster in Aspergillus fumigatus.
AB  - In the human pathogenic mold Aspergillus fumigatus, sexual identity is determined
      by the mating-type idiomorphs MAT1-1 and MAT1-2 residing at the MAT locus. Upon
      crossing of compatible partners, a heterothallic mating is executed to eventually
      form cleistothecia that contain recombinant ascospores. Given that the MAT1 gene
      products are DNA binding master regulators that govern this complex developmental
      process, we monitored the MAT1-driven transcriptomes of A. fumigatus by
      conditional overexpression of either MAT1 gene followed by RNA-seq analyses.
      Numerous genes related to the process of mating were found to be under
      transcriptional control, such as pheromone production and recognition.
      Substantial differences between the MAT1-1- and MAT1-2-driven transcriptomes
      could be detected by functional categorization of differentially expressed genes.
      Moreover, a significant and distinct impact on expression of genetic clusters of
      secondary metabolism became apparent, which could be verified on the product
      level. Unexpectedly, specific cross-regulation of the fumagillin/pseurotin
      supercluster was evident, thereby uncoupling its co-regulatory characteristic.
      These insights imply a tight interconnection of sexual development accompanied by
      ascosporogenesis with secondary metabolite production of a pathogenic fungus and
      impose evolutionary constraints that link these two fundamental aspects of the
      fungal lifestyle.

PMID- 30240514
TI  - Phase-locked responses to the vowel envelope vary in scalp-recorded amplitude due
      to across-frequency response interactions.
AB  - Neural encoding of the envelope of sounds like vowels is essential to access
      temporal information useful for speech recognition. Subcortical responses to
      envelope periodicity of vowels can be assessed using scalp-recorded envelope
      following responses (EFRs); however, the amplitude of EFRs vary by vowel spectra
      and the causal relationship is not well understood. One cause for spectral
      dependency could be interactions between responses with different phases,
      initiated by multiple stimulus frequencies. Phase differences can arise from
      earlier initiation of processing high frequencies relative to low frequencies in
      the cochlea. This study investigated the presence of such phase interactions by
      measuring EFRs to two naturally spoken vowels (/epsilon/ and /u/), while delaying
      the envelope phase of the second formant band (F2+) relative to the first formant
      (F1) band in 45 degrees  increments. At 0 degrees  F2+ phase delay, EFRs elicited
      by the vowel /epsilon/ were lower in amplitude than the EFRs elicited by /u/.
      Using vector computations, we found that the lower amplitude of /epsilon/-EFRs
      was caused by linear superposition of F1- and F2+-contributions with larger F1
      F2+ phase differences (166 degrees ) compared to /u/ (19 degrees ). While the
      variation in amplitude across F2+ phase delays could be modeled with two dominant
      EFR sources for both vowels, the degree of variation was dependent on F1 and F2+
      EFR characteristics. Together, we demonstrate that (a) broadband sounds like
      vowels elicit independent responses from different stimulus frequencies that may
      be out-of-phase and affect scalp-based measurements, and (b) delaying higher
      frequency formants can maximize EFR amplitudes for some vowels.

PMID- 30240516
TI  - Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy
      of an orexin/hypocretin-1 receptor antagonist in rats.
AB  - Behavioral economics is a powerful, translational approach for measuring drug
      demand in both humans and animals. Here, we asked if demand for cocaine in rats
      with limited drug experience could be used to identify individuals most at risk
      of expressing an addiction phenotype following either long- or intermittent
      access self-administration schedules, both of which model the transition to
      uncontrolled drug-seeking. Because the orexin-1 receptor antagonist SB-334867
      (SB) is particularly effective at reducing drug-seeking in highly motivated
      individuals, we also asked whether demand measured after prolonged drug
      experience could predict SB efficacy. Demand elasticity (alpha) measured
      immediately following acquisition of cocaine self-administration ('baseline
      alpha') was positively correlated with alpha assessed after 2w of long- or
      intermittent access. Baseline alpha also predicted the magnitude of compulsive
      responding for cocaine, drug-seeking in initial abstinence and cued reinstatement
      following long-, intermittent- or standard short access. When demand was measured
      after these differential access conditions, alpha predicted the same addiction
      endophenotypes predicted by baseline alpha, as well as primed reinstatement and
      the emergence of negative emotional mood behavior following abstinence. alpha
      also predicted the efficacy of SB, such that high demand rats showed greater
      reductions in motivation for cocaine following SB compared to low demand rats.
      Together, these findings indicate that alpha might serve as a behavioral
      biomarker to predict individuals most likely to progress from controlled to
      uncontrolled drug use, and to identify individuals most likely to benefit from
      orexin-based therapies for the treatment of addiction.

PMID- 30240515
TI  - Longitudinal changes in kidney function following heart transplantation: Stanford
      experience.
AB  - Many heart transplant recipients experience declining kidney function following
      transplantation. We aimed to quantify change in kidney function in heart
      transplant recipients stratified by pre-transplant kidney function. A total of
      230 adult heart transplant recipients between May 1, 2008, and December 31, 2014,
      were evaluated for up to 5 years post-transplant (median 1 year). Using 19 398
      total estimated glomerular filtration rate (eGFR) assessments, we evaluated
      trends in eGFR in recipients with normal/near-normal (eGFR >=45 mL/min/1.73 m2 )
      vs impaired (eGFR <45 mL/min/1.73 m2 ) kidney function and the likelihood of
      reaching an eGFR of 20 mL/min/1.73 m2 after heart transplant. Baseline
      characteristics were similar. Immediately following heart transplant, the
      impaired pre-transplant kidney function group showed a mean eGFR gain of 9.5
      mL/min/1.73 m2 (n = 193) vs a mean decline of 4.9 mL/min/1.73 m2 (n = 37) in the
      normal/near-normal group. Subsequent rates of eGFR decline were 2.2 mL/min/1.73
      m2 /y vs 2.9 mL/min/1.73 m2 /y, respectively. The probability of reaching an eGFR
      of 20 mL/min/1.73 m2 or less at 1, 5, and 10 years following heart transplant was
      1%, 4%, and 30% in the impaired group, and <1%, <1%, and 10% in the normal/near
      normal group. Estimates of expected recovery in kidney function and its decline
      over time will help inform decision making about kidney care after heart
      transplantation.

PMID- 30240517
TI  - Capturing violent radicalization: Developing and validating scales measuring
      central aspects of radicalization.
AB  - Violent radicalization has emerged as an important topic of theoretical and
      empirical investigation motivated by the devastating face of terrorism and by the
      aim of preventing such expressions of extremism. One central aspect of such
      research inquiries is the foundation of solid measurement. In this article, we
      develop and validate two generic scales pertaining to (1) endorsement of
      extremism and (2) acceptance of violent and/or illegal means. In conclusion, the
      scales yielded sound psychometric properties and cross-cultural equivalence,
      providing a solid measure of the important aspects of extremism which can be
      empirically employed in elucidating generic mechanisms of violent radicalization
      processes.

PMID- 30240518
TI  - Glial mechanisms underlying substance use disorders.
AB  - Addiction is a devastating disorder that produces persistent maladaptive changes
      to the central nervous system, including glial cells. Although there is an
      extensive body of literature examining the neuronal mechanisms of substance use
      disorders, effective therapies remain elusive. Glia, particularly microglia and
      astrocytes, have an emerging and meaningful role in a variety of processes beyond
      inflammation and immune surveillance, and may represent a promising therapeutic
      target. Indeed, glia actively modulate neurotransmission, synaptic connectivity
      and neural circuit function, and are critically poised to contribute to addictive
      like brain states and behaviors. In this review, we argue that glia influence the
      cellular, molecular, and synaptic changes that occur in neurons following drug
      exposure, and that this cellular relationship is critically modified following
      drug exposure. We discuss direct actions of abused drugs on glial function
      through immune receptors, such as Toll-like receptor 4, as well as other
      mechanisms. We highlight how drugs of abuse affect glia-neural communication, and
      the profound effects that glial-derived factors have on neuronal excitability,
      structure, and function. Recent research demonstrates that glia have brain region
      specific functions, and glia in different brain regions have distinct
      contributions to drug-associated behaviors. We will also evaluate the evidence
      demonstrating that glial activation is essential for drug reward and drug-induced
      dopamine release, and highlight clinical evidence showing that glial mechanisms
      contribute to drug abuse liability. In this review, we synthesize the extensive
      evidence that glia have a unique, pivotal, and underappreciated role in the
      development and maintenance of addiction.

PMID- 30240520
TI  - Hypercalcemia and cancer: Differential diagnosis and treatment.
AB  - Incidentally detected hypercalcemia usually presents in an indolent manner and is
      most likely caused by primary hyperparathyroidism. In contrast, hypercalcemia in
      the patient with a history of cancer presents in a wide range of clinical
      settings and may be severe enough to warrant hospitalization. This form of
      hypercalcemia is usually secondary to hypercalcemia of malignancy and can be
      fatal. Hypercalcemia of malignancy is most commonly mediated by tumoral
      production of parathyroid hormone-related protein or by cytokines activating
      osteoclast degradation of bone. The initial workup, differential diagnoses,
      confirmatory laboratory testing, imaging, and medical and surgical management of
      hypercalcemia are described in the patient with cancer.

PMID- 30240519
TI  - Evaluation of Normal-Appearing White Matter in Multiple Sclerosis Using Direct
      Visualization of Short Transverse Relaxation Time Component (ViSTa) Myelin Water
      Imaging and Gradient Echo and Spin Echo (GRASE) Myelin Water Imaging.
AB  - BACKGROUND: In multiple sclerosis (MS), not only lesions but also normal MRI
      appearing white matter (NAWM) may undergo demyelination. PURPOSE: To demonstrate
      the detection of NAWM demyelination using direct visualization of short
      transverse relaxation time component myelin water imaging (ViSTa-MWI) and to
      compare the results with those of conventional gradient echo and spin echo
      (GRASE)-MWI. STUDY TYPE: Control/cohort. POPULATION: Twenty-five MS patients and
      18 healthy controls (HC). FIELD STRENGTH/SEQUENCE: 3T/ViSTa and GRASE-MWI.
      ASSESSMENT: Using ViSTa and GRASE-MWI, myelin water fraction (MWF) of NAWM or
      normal WM was compared between MS (all patients or early-stage MS patients) and
      HC. The comparison was performed for a global WM mask and five regional WM masks.
      STATISTICAL TESTS: A general linear model was applied for the comparison. A
      statistical power and a minimum sample size for the significant difference were
      obtained. Spearman's correlation coefficient was calculated between MWF and
      clinical measures and between ViSTa-MWF and GRASE-MWF for the global WM mask.
      RESULTS: MWFs of ViSTa were significantly lower in the MS patients than those in
      the HC in all masks (P < 0.001). GRASE-MWI results revealed reduced MWFs only in
      global WM, genu, and optic radiation. ViSTa-MWI had higher statistical powers
      than that of GRASE-MWI (power: ViSTa = 99.2 +/- 1.6% and GRASE = 75.5 +/- 31.0%;
      sample size: ViSTa = 18 +/- 9 and GRASE = 78 +/- 75). In early-stage MS, MWFs of
      ViSTa were significantly lower than those of the HC in all masks except for
      centrum semiovale; however, MWFs of GRASE MWI were significantly lower only in
      optic radiation. Disease duration was correlated with both MWIs (ViSTa; r = 
      0.437 and GRASE; r = -0.445). ViSTa and GRASE MWFs were significantly correlated
      in the HC (r = 0.664) and MS (r = 0.768). DATA CONCLUSION: ViSTa-MWI may detect a
      reduction of MWF in NAWM of MS. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1
      J. Magn. Reson. Imaging 2018.

PMID- 30240521
TI  - The American College of Chest Physician score to assess the risk of bleeding
      during anticoagulation in patients with venous thromboembolism: reply.

PMID- 30240523
TI  - The moderating role of race/ethnicity on associations between insurance status
      and HPV vaccination among women in the USA.
AB  - OBJECTIVE: To evaluate associations between insurance status and HPV vaccination.
      METHODS: The present cross-sectional study analyzed data from women aged 18-26
      years who participated in the National Health and Nutritional Examination Surveys
      2009-2012 in the USA. RESULTS: The study included 621 women; 424 (68.3%) had some
      type of insurance and 198 (30.6%) had received the HPV vaccine. In the
      multivariable model, we found significant interactions between race/ethnicity and
      insurance status on receiving HPV vaccination. Compared with individuals with no
      insurance, non-Hispanic black women with any type of insurance demonstrated
      increased likelihood of HPV vaccination (adjusted odds ratio [aOR] 3.63, 95%
      confidence interval [CI] 1.60-8.21; P=0.002). Among Mexican Americans, there was
      a negative association between having some insurance and HPV vaccination (aOR
      0.35, 95% CI 0.15-0.81; P=0.007). For non-Hispanic black women, the association
      remained significant across all insurance types (private [aOR 4.29, 95% CI 1.67
      11.00; P=0.003], Medicaid [aOR 2.86, 95% CI 1.15-7.13; P=0.025], and other [aOR
      4.74, 95% CI 1.06-21.15; P=0.042]). Non-Hispanic white women with insurance other
      than private or Medicaid had a higher likelihood of HPV vaccination compared with
      uninsured individuals (aOR 8.36, 95% CI 2.79-25.05; P<0.001). CONCLUSION: The
      present findings help to identify at-risk populations less likely to receive the
      HPV vaccine.

PMID- 30240524
TI  - Effects of low doses Trichlorfon exposure on Rana chensinensis tadpoles.
AB  - Trichlorfon is an organophosphate insecticide widely used in aquaculture and
      agriculture. Little is known about the effects of long-term of low doses
      trichlorfon exposure on amphibians. In this study, we investigated the effects of
      low doses trichlorfon on Rana chensinensis tadpoles after exposure to 0.01, 0.1,
      and 1.0 mg/L trichlorfon for 2 and 4 weeks. Survival, growth, development and
      mortality were monitored regularly over the course of exposure. The results
      showed that trichlorfon led to a decrease in tadpole survival. Reductions in
      growth and disruptions to the development of tadpoles were observed in
      trichlorfon treatments. Morphological abnormalities of affected tadpoles included
      axial flexures, skeletal malformations and lateral kinks. Trichlorfon increased
      the frequency of micronucleus (MN) formation in circulating erythrocytes of
      tadpoles exposed for 2 weeks to 0.1 and 1.0 mg/L trichlorfon. At all
      concentrations, an enhanced frequency of MN formation was observed in tadpoles
      exposed for 4 weeks. Exposure to trichlorfon induced other nuclear abnormalities
      such as lobed and notched nuclei only in tadpoles exposed to 1.0 mg/L trichlorfon
      for 4 weeks. In addition, exposure to trichlorfon within the 0.01-1.0 mg/L range
      increased the genetic damage index in hepatic tissues in all treatments.
      Apoptosis-associated DNA fragmentation in hepatic tissues occurred in a weak
      ladder-like pattern. This study presents evidence of low doses trichlorfon
      effects on amphibians, highlighting the properties of this organophosphate
      insecticide that jeopardize nontarget species exposed to trichlorfon.

PMID- 30240522
TI  - A Metal-Organic Framework with Suitable Pore Size and Specific Functional Sites
      for the Removal of Trace Propyne from Propylene.
AB  - Separation of propyne/propylene (C3 H4 /C3 H6 ) is more difficult and challenging
      than that of acetylene/ethylene (C2 H2 /C2 H4 ) because of their closer molecular
      sizes. A comprehensive screening of a series of metal-organic frameworks with
      broad types of structures, pore sizes, and functionalities was carried out. UTSA
      200 was identified as the best separating material for the removal of trace C3 H4
      from C3 H4 /C3 H6 mixtures. Gas sorption isotherms reveal that UTSA-200 exhibits
      by far the highest C3 H4 adsorption capacity (95 cm3  cm-3 at 0.01 bar and 298 K)
      and record C3 H4 /C3 H6 selectivity, which was mainly attributed to the suitable
      dynamic pore size to efficiently block the larger C3 H6 molecule whilst the
      strong binding sites and pore flexibility capture smaller C3 H4 . This material
      thus provides record purification capacity for the removal of C3 H4 from a 1:99
      (or 0.1:99.9, v/v) C3 H4 /C3 H6 mixture to produce 99.9999 % pure C3 H6 with a
      productivity of 62.0 (or 142.8) mmol g-1 .

PMID- 30240525
TI  - Analysis of MRI Values and Hemoglobin and Total Protein Concentrations of Cystic
      Ovarian Tumors.
AB  - BACKGROUND: Endometrioma generally shows higher intracystic signal intensity (SI)
      than mucinous cystadenoma (MCA) on T1 -weighted imaging (T1 WI). Nonendometrioma
      associated malignant ovarian epithelial tumors (nonendometrioma group) often show
      higher intracystic SI than benign tumors on T1 WI, while the converse is true for
      endometrioma and endometrioma-associated malignant tumors (endometrioma group).
      However, it is sometimes difficult to differentiate between hemorrhagic and
      mucinous content based on SI on T1 WI. Hemoglobin (Hb) and protein are both
      speculated to shorten T1 . PURPOSE: To examine MRI values and Hb and total
      protein (TP) concentrations in ovarian tumors. STUDY TYPE: Prospective. SPECIMEN:
      In all, 182 samples from 167 cystic ovarian tumors. FIELD STRENGTH: 1.5T, spin
      echo T1 WI, fast spin-echo T2 WI. ASSESSMENT: The in vivo intracystic/psoas major
      muscle SI ratios were determined as references for intracystic SI. T1 and T2
      values, cystic content inversion times (TIs), and Hb and TP concentrations were
      determined to evaluate differences between 1) endometrioma and MCA; 2) benign,
      borderline, and malignant tumors in the nonendometrioma group; and 3) those in
      the endometrioma group. STATISTICAL TESTS: Wilcoxon's rank-sum test, Kruskal
      Wallis test. RESULTS: In endometriomas (n = 43) and MCAs (n = 27), mean T1 and T2
      (TP, Hb concentrations) were 428 and 162 msec (52.7, 12.00 g/dl) and 1639 and 600
      msec (7.1, 0.06 g/dl), respectively (all, P < 0.0001). In the nonendometrioma
      group (epithelial benign, n = 56; borderline, n = 20; malignant, n = 25), these
      values were 1657 and 696 msec (6.4, 0.35 g/dl), 1235 and 400 msec (13.5, 0.83
      g/dl), and 1184 and 311 msec (19.7, 0.84 g/dl), respectively (all, P < 0.0001).
      In the endometrioma group (endometrioma, n = 43; borderline, n = 3; malignant, n
      = 8), these values were 428 and 162 msec (52.7, 12.00 g/dl), 427 and 108 msec
      (16.6, 3.07 g/dl), and 1010 and 268 msec (24.2, 1.56 g/dl), respectively (all, P
      < 0.05). DATA CONCLUSION: TP and Hb concentrations were higher in the contents of
      endometriomas than MCAs, leading to lower T1 and T2 values. In the
      nonendometrioma group, TP and Hb concentrations were higher in the cystic
      contents of borderline and malignant tumors than benign tumors, leading to lower
      T1 and T2 values. Conversely, the cystic contents of borderline and malignant
      tumors in the endometrioma group showed lower TP and Hb concentrations compared
      to endometriomas, leading to higher T1 and T2 values. LEVEL OF EVIDENCE: 2
      Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 30240526
TI  - Improving decision-making and cognitive impulse control in bulimia nervosa by
      rTMS: An ancillary randomized controlled study.
AB  - OBJECTIVE: Impaired decision-making and inhibitory control may be involved in the
      pathophysiology of psychiatric disorders like bulimia nervosa (BN). Their
      improvement after neuromodulation may underpin clinical improvement. We assessed
      the effects of rTMS on these cognitive functions in a sample of women with BN.
      METHODS: Thirty-nine participants (22 in a sham group and 17 in an rTMS group)
      were assessed before and after 10 high frequency rTMS sessions over the left
      dorsolateral prefrontal cortex (DLPFC). RESULTS: The between-group analyses
      revealed no differences in the final neuropsychological performances. The within
      group analyses showed that inhibitory control improved in both the go/no-go task
      (p = .03) and the BIS cognitive impulsivity subscale (p = .01) in the rTMS group
      only. Switches toward good choices on the Iowa gambling task significantly
      improved in the rTMS group only (p = .002), and understanding of the task
      contingencies increased between the two assessments, also in the rTMS group only
      (p = .03). DISCUSSION: This preliminary evidence suggests that modulation of left
      DLPFC might improve two putative cognitive biomarkers of BN.

PMID- 30240527
TI  - Short-course carbon-ion radiotherapy for hepatocellular carcinoma: A multi
      institutional retrospective study.
AB  - BACKGROUND & AIMS: Carbon-ion radiation therapy has shown encouraging results in
      hepatocellular carcinoma patients in single-centre studies. We evaluated the
      effectiveness and safety of short-course carbon-ion radiation therapy for
      hepatocellular carcinoma in a multicentre study conducted by the Japan Carbon Ion
      Radiation Oncology Study Group. METHODS: Consecutive hepatocellular carcinoma
      patients who were treated with carbon-ion radiation therapy in four or fewer
      fractions at four Japanese institutions between April 2005 and November 2014 were
      analysed retrospectively. The primary outcome was overall survival; secondary
      outcomes were local control rate, treatment-related toxicity and radiation
      induced liver disease. RESULTS: A total of 174 patients were included in this
      study. Prescribed carbon-ion radiation therapy doses were (relative biological
      effectiveness): 48.0 Gy in two fractions (n = 46), and 52.8 Gy (n = 108) and 60.0
      Gy (n = 20) in four fractions. The median follow-up period was 20.3 (range, 2.9
      103.5) months. The overall survival and local control rates at 1, 2 and 3 years
      were 95.4%, 82.5% and 73.3%; and 94.6%, 87.7% and 81.0% respectively.
      Multivariate analysis revealed that Eastern Cooperative Oncology Group
      performance status 1-2, Child-Pugh class B, maximum tumour diameter >=3 cm,
      multiple tumours and serum alpha foetoprotein level >50 ng/mL were significant
      prognostic factors of overall survival. No treatment-related death occurred
      during the follow-up period. Grades 3 or 4 treatment-related toxicities were
      observed in 10 patients (5.7%); radiation-induced liver disease was observed in
      three patients (1.7%). CONCLUSIONS: Short-course carbon-ion radiation therapy is
      a safe, effective and potentially curative therapy for hepatocellular carcinoma.

PMID- 30240528
TI  - Resolving power in liquid chromatography: A trade-off between efficiency and
      analysis time.
AB  - This review describes chromatographic dispersion and different plate-height
      models frequently used to assess the chromatographic performance of ultra-high
      pressure liquid chromatography column technology. Furthermore, different
      performance indices, including the resolution, the separation impedance, and
      kinetic plots are discussed allowing to quantify and visualize the resolving
      power in liquid chromatography. The construction of kinetic plots is explained,
      and different visualization approaches are highlighted. Finally, key instrument
      and column-technology developments to advance the kinetic performance limits are
      discussed and selected state-of-the-art applications are highlighted.

PMID- 30240529
TI  - Difference in the generalization of response tolerance across views between the
      anterior and posterior part of the inferotemporal cortex.
AB  - The inferotemporal cortex consists of an anterior (cytoarchitectonic area TE) and
      a posterior (area TEO) part, which together constitute the final areas of the
      ventral visual stream, which is critical for object discrimination. Area TE
      receives dense projections from area TEO. We have previously identified a
      response tolerance in the cells in area TE in monkeys to a range of viewing
      angles after object discrimination at each of several views. To investigate the
      contribution of area TEO to the establishment of such a response tolerance in
      area TE, we conducted electrophysiological recordings of the responses of the
      single cells in area TEO after performance saturation of object discrimination at
      several independent views, without any association across views, and compared
      them with those obtained from the TE cells. The cells in area TEO showed
      responses to the experienced object views, but not to nearby views. Comparisons
      of the tunings of the TE and TEO cells to different viewing angles for the same
      object sets in the same animal showed that cells in area TEO had a significantly
      narrower tuning width, whereas the response tolerance was usually observed in the
      TE cells across viewing angles up to 60 degrees . Our findings revealed a
      significant difference in the representation of the object views between areas TE
      and TEO, and suggested that such a representation in area TE may be completed
      through neuronal mechanisms within area TE, which is not a property of the
      earlier stages of the ventral visual stream.

PMID- 30240530
TI  - Activation of the neural pathway from the dorsolateral bed nucleus of the stria
      terminalis to the central amygdala induces anxiety-like behaviors.
AB  - The bed nucleus of the stria terminalis (BNST) and the central amygdala (CeA)
      comprise a forebrain unit that has been described as the "extended amygdala".
      These two nuclei send dense projections to each other and have been implicated in
      the regulation of negative emotional states, including anxiety and fear. The
      present study employed an optogenetic technique to examine whether stimulation of
      CeA-projecting dorsolateral BNST (dlBNST) neuron terminals would influence
      anxiety-like behaviors in male Sprague-Dawley rats. Photostimulation of CeA
      projecting dlBNST neuron terminals produced anxiogenic effects in an elevated
      plus maze test. This finding is inconsistent with previous reports showing that
      optogenetic stimulation of BNST neurons projecting to the lateral hypothalamus
      (LH) and ventral tegmental area (VTA) produces anxiolytic rather than anxiogenic
      effects. To address this issue, electrophysiological analyses were conducted to
      characterize dlBNST neurons projecting to the CeA, LH, and VTA. dlBNST neurons
      can be electrophysiologically classified into three distinct cell types (types I
      III) according to their responses to depolarizing and hyperpolarizing current
      injections. Whole-cell patch-clamp recordings revealed that more than 60% of the
      CeA-projecting dlBNST neurons were type II, whereas approximately 80% of the LH-
      and VTA-projecting dlBNST neurons were type III. These electrophysiological
      results will help elucidate the mechanisms underlying the heterogeneity of BNST
      neurons during the regulation of anxiety-like behaviors.

PMID- 30240531
TI  - Reply Letter 17-2110.R2.
AB  - The prognostic value of MELD in the setting of acute variceal bleeding is largely
      known. Indeed, a MELD-based model (calibrated-MELD) accurately assigns a
      probability of 6 weeks mortality for each value of MELD3 . However, when
      selecting patients for preemptive-TIPS, selection based on Child and active
      bleeding is the only proven strategy that improves outcome and increases
      survival. This article is protected by copyright. All rights reserved.

PMID- 30240532
TI  - Challenges in delivery and performance of a cervical cancer prevention program in
      the Kurdistan Region of the Iraq health system.
AB  - OBJECTIVE: To investigate health-system challenges responsible for the poor
      performance of a cervical cancer prevention program in the Kurdistan Region of
      Iraq. METHOD: A qualitative study was conducted among a purposive sample of
      healthcare providers and female volunteers in Erbil, Kurdistan Region of Iraq,
      between December 10, 2014, and July 23, 2016. Data were collected from
      participants using in-depth semi-structured interviews. The interviews were then
      transcribed and analyzed with an inductive content analysis approach. RESULTS: In
      total, 23 individuals completed the interviews. The participants included 8 (35%)
      female volunteers; 5 (22%) nurses; 4 (17%) managers; 3 (13%) doctors; and 3 (13%)
      gynecologists. The health-system challenges were classified into three main
      categories: existence of an official reminder system, public information delivery
      programs, and infrastructures of facilities, which included three subcategories
      cervical cancer screening center, material resources, and human resources.
      CONCLUSIONS: The Kurdistan Region of Iraq health system faced several challenges
      in delivering a cervical cancer prevention program. These challenges must be
      addressed to improve the coverage of cervical cancer screening, diagnosis, and
      treatment.

PMID- 30240533
TI  - Education, and the balance between dynamic and stationary functional connectivity
      jointly support executive functions in relapsing-remitting multiple sclerosis.
AB  - Graphical network characteristics and nonstationary functional connectivity
      features, both derived from resting-state functional magnetic resonance imaging
      (rsfMRI) data, have been associated with cognitive performance in healthy
      subjects. How these features jointly relate to cognition in diseased states has
      not been investigated. In this study, 46 relapsing-remitting multiple sclerosis
      subjects underwent rsfMRI scans and a focused cognitive battery. With a sliding
      window approach, we examined six dynamic network features that indicated how
      connectivity changed over time as well as six measures derived from graph theory
      to reflect static network characteristics. Multiset canonical correlation
      analysis (MCCA) was then carried out to investigate the relations between dynamic
      network features, stationary network characteristics, cognitive testing,
      demographic, disease severity, and mood. Multiple sclerosis (MS) subjects
      demonstrated weaker connectivity strength, decreased network density, reduced
      global changes, but increased changes in interhemispheric connectivity compared
      to controls. The MCCA model determined that executive functions and processing
      speed ability measured by Wechsler Adult Intelligence Scale IV (WAIS-IV) Working
      Memory Index, WAIS-IV Processing Speed Index, and the Verbal Fluency Test were
      positively correlated with education, dynamic connectivity, and static
      connectivity strength; while poor task switching was correlated with disease
      severity, psychiatric comorbidities such as depression, anxiety, and fatigue, and
      static network density. Taken together, our results suggest that better executive
      functioning in MS requires maintenance of a continued coordination between
      stationary and dynamic functional connectivity as well as the support of
      education, and dynamic functional connectivity may provide an additional
      cognitive biomarker of disease severity in the MS population.

PMID- 30240534
TI  - Antibody adsorption in protein-A affinity chromatography - in situ measurement of
      nanoscale structure by small-angle X-ray scattering.
AB  - Protein-A chromatography is the most widely used chromatography step in
      downstream processing of antibodies. A deeper understanding of the influence of
      the surface topology on a molecular/nanoscale level on adsorption is essential
      for further improvement. It is not clear if the binding is homogenous throughout
      the entire bead network. We followed the protein absorption process and observed
      the formation of a protein layer on fibers of chromatography resin in a time
      resolved manner in nanoscale. To characterize the changes in the antibody-protein
      A ligand complex, small angle X-ray scattering was employed using a miniaturized
      X-ray-transparent chromatography column packed with a MabSelect SuRe resin.
      Antibody-free MabSelect SuRe resin fiber had an average radius of 12 nm and the
      protein layer thickness resulting from antibody adsorption was 5.5 and 10.4 nm
      for fiber and junctions, respectively under applied native conditions. We
      hypothesize that an average of 1.2 antibodies were adsorbed per protein-A ligand
      tetramer bound to the outermost units. In contrast to previous studies, it was
      therefore possible for the first time to directly correlate the nanostructure
      changes inside the column, which is otherwise a black box, with the adsorption
      and elution process.

PMID- 30240535
TI  - Melatonin as adjunctive therapy in the treatment of periodontitis associated with
      obesity.
AB  - AIMS: To study the effect of adjunctive systemic administration of melatonin to
      standard mechanical periodontal therapy in obese rats with experimental
      periodontitis. MATERIALS AND METHODS: In 42 Wistar rats with an initial body
      weight of 180 g., half (n = 21) were fed with a high-fat diet to induce obesity.
      In both obese and normal-weight groups, experimental periodontitis was
      subsequently induced through oral gavages with a combination of Porphyromonas
      gingivalis and Fusobacterium nucleatum. Both groups were randomly allocated to
      either no treatment or periodontal treatment consisting on standard mechanical
      debridement, with either adjunctive chlorhexidine or melatonin. Outcomes were
      evaluated by the changes in clinical parameters (probing depth modified gingival
      index, plaque dental index and bleeding on probing [BOP]), in bone resorption and
      in the levels of biomarkers in plasma and in gingival tissue (inflammatory
      cytokines, insulin, leptin, osteocalcin, osteopontin, plasminogen activator
      inhibitor-1, intercellular adhesion molecule 1, E-selectin and lipids). RESULTS:
      In the obese-periodontitis group, adjunctive melatonin administration resulted in
      reduced gingival inflammation and BOP, with significant reductions in probing
      depth and enhanced bone repair demonstrated by micro-CT (15% reduction in
      alveolar bone destruction) when compared with the same group treated with
      adjunctive CHX or the normal-weight rats with either melatonin or CHX. In this
      melatonin-treated obese-periodontitis group, a significant impact on biochemical
      biomarkers was also demonstrated in both gingival and plasma samples, when
      compared with the other groups, with significant reductions in pro-inflammatory
      cytokines. CONCLUSIONS: Adjunctive melatonin therapy significantly reduced
      alveolar bone loss and exerted a protective anti-inflammatory effect mainly in
      those experimental animals affected by the co-morbidity of periodontitis and
      obesity.

PMID- 30240536
TI  - Laparoscopic vs open resection of pT4 colon cancer: a propensity score analysis
      of 94 patients.
AB  - AIM: Our aim was to compare short- and long-term oncological outcomes between
      laparoscopic and open colectomy in T4 colon cancer. METHODS: We retrospectively
      analysed oncological outcomes of 94 patients who underwent surgery between
      December 2010 and December 2016 for pT4 colon cancer, with propensity score
      matching. All patients were treated with curative intent, by either laparoscopic
      or open en bloc resection. RESULTS: The conversion rate in the laparoscopic group
      was 17.0%. Blood loss, time to flatus and postoperative hospitalization were
      significantly less in the laparoscopic group. Postoperative morbidity and
      mortality within 30 days did not significantly differ between the two groups. R0
      resection rates and lymph node harvests were similar between the two groups. At 5
      years, laparoscopic outcomes were not inferior to open outcomes (overall survival
      56.8% vs 50.2%, P = 0.250; disease-free survival 59.7% vs 41.7%, P = 0.06).
      CONCLUSION: The laparoscopic approach is safe and feasible for pathologically
      confirmed T4 colon cancer. It results in a faster postoperative recovery.

PMID- 30240537
TI  - Current review of TP53 pathogenic germline variants in breast cancer patients
      outside Li-Fraumeni syndrome.
AB  - Pathogenic germline variants in TP53 predispose carriers to the multi-cancer Li
      Fraumeni syndrome (LFS). Widespread multigene panel testing is identifying TP53
      pathogenic variants in breast cancer patients outside the strict clinical
      criteria recommended for LFS testing. We aimed to assess frequency and clinical
      implications of TP53 pathogenic variants in breast cancer cohorts ascertained
      outside LFS. Classification of TP53 germline variants reported in 59 breast
      cancer studies, and publicly available population control sets was reviewed and
      identified evidence for misclassification of variants. TP53 pathogenic variant
      frequency was determined for: breast cancer studies grouped by ascertainment
      characteristics; breast cancer cohorts undergoing panel testing; and population
      controls. Early age of breast cancer onset, regardless of family history or
      BRCA1/BRCA2 previous testing, had the highest pick-up rate for TP53 carriers.
      Patients at risk of hereditary breast cancer unselected for features of LFS
      carried TP53 pathogenic variants at a frequency comparable to that of other non
      BRCA1/2 breast cancer predisposing genes, and ~threefold more than reported in
      population controls. These results have implications for the implementation of
      TP53 testing in broader clinical settings, and suggest urgent need to investigate
      cancer risks associated with TP53 pathogenic variants in individuals outside the
      LFS spectrum.

PMID- 30240539
TI  - Going under down under? Lineage ages argue for extensive survival of the
      Oligocene marine transgression on Zealandia.
AB  - Twenty-five years ago, it was suggested that current-day New Zealand, part of the
      largely sunken continent of Zealandia, could have been completely inundated
      during the Oligocene marine transgression (OMT) some 25-23 million years ago.
      Such an event would, of necessity, imply that all terrestrial, freshwater, and
      maybe coastal marine species must have dispersed there since. This idea has
      generated heated debate, on which geological, palaeontological and molecular data
      are being brought to bear. Here, we review the phylogeographic literature in the
      form of molecular estimates of divergence times between New Zealand lineages and
      their closest overseas sister groups. Using an event-based approach, we show that
      these divergence times follow approximately a smooth exponential over the last 50
      Ma or more. Approximately 74 of these 248 lineages appear to have survived the
      OMT in situ; some of these major lineages comprise multiple additional lineages
      as a result of autochthonous speciation prior to the OMT. Non-volant terrestrial
      animals, freshwater animals and trees are particularly well represented in
      surviving lineages, whereas marine animals, herbs and shrubs tend to show more
      recent arrival times. There is no evidence for a deficit of pre-Oligocene
      lineages, nor an excess of ones arriving just afterwards. The pattern is one of
      geometric increase in new lineages with more recent time, reflecting a balance
      between immigration and extinction. Consequently, this large body of molecular
      data provides no evidence for complete inundation of New Zealand during the
      Oligocene. In conjunction with new geological and palaeontological findings,
      these data suggest that it is time to put the idea to rest.

PMID- 30240538
TI  - Oral administration of alcalase potato protein hydrolysate-APPH attenuates high
      fat diet-induced cardiac complications via TGF-beta/GSN axis in aging rats.
AB  - Consumption of high fat diet (HFD) is associated with increased cardiovascular
      risk factors among elderly people. Aging and obesity induced-cardiac remodeling
      includes hypertrophy and fibrosis. Gelsolin (GSN) induces cardiac hypertrophy and
      TGF-beta, a key cytokine, which induces fibrosis. The relationship between TGF
      beta and GSN in aging induced cardiac remodeling is still unknown. We evaluated
      the expressions of TGF-beta and GSN in HFD fed 22 months old aging SD rats,
      followed by the administration of either probucol or alcalase potato protein
      hydrolysate (APPH). Western blotting and Masson trichrome staining showed that
      APPH (45 and 75 mg/kg/day) and probucol (500 mg/kg/day) treatments significantly
      reduced the aging and HFD-induced hypertrophy and fibrosis. Echocardiograph
      showed that the performance of the hearts was improved in APPH, and probucol
      treated HFD aging rats. Serum from all rats was collected and H9c2 cells were
      cultured with collected serums separately. The GSN dependent hypertrophy was
      inhibited with an exogenous TGF-beta in H9c2 cells cultured in HFD+ APPH treated
      serum. Thus, we propose that along with its role in cardiac fibrosis, TGF-beta
      also acts as an upstream activator of GSN dependent hypertrophy. Hence, TGF-beta
      in serum could be a promising therapeutic target for cardiac remodeling in aging
      and/or obese subjects.

PMID- 30240540
TI  - Effect of an online program using popular social media on healthcare
      professionals' knowledge and attitudes towards dementia.

PMID- 30240541
TI  - Hypothyroidism-induced hypermagnesemia with a small dose of magnesium.

PMID- 30240542
TI  - The neural oscillatory markers of phonetic convergence during verbal interaction.
AB  - During a conversation, the neural processes supporting speech production and
      perception overlap in time and, based on context, expectations and the dynamics
      of interaction, they are also continuously modulated in real time. Recently, the
      growing interest in the neural dynamics underlying interactive tasks, in
      particular in the language domain, has mainly tackled the temporal aspects of
      turn-taking in dialogs. Besides temporal coordination, an under-investigated
      phenomenon is the implicit convergence of the speakers toward a shared phonetic
      space. Here, we used dual electroencephalography (dual-EEG) to record brain
      signals from subjects involved in a relatively constrained interactive task where
      they were asked to take turns in chaining words according to a phonetic rhyming
      rule. We quantified participants' initial phonetic fingerprints and tracked their
      phonetic convergence during the interaction via a robust and automatic speaker
      verification technique. Results show that phonetic convergence is associated to
      left frontal alpha/low-beta desynchronization during speech preparation and by
      high-beta suppression before and during listening to speech in right centro
      parietal and left frontal sectors, respectively. By this work, we provide
      evidence that mutual adaptation of speech phonetic targets, correlates with
      specific alpha and beta oscillatory dynamics. Alpha and beta oscillatory dynamics
      may index the coordination of the "when" as well as the "how" speech interaction
      takes place, reinforcing the suggestion that perception and production processes
      are highly interdependent and co-constructed during a conversation.

PMID- 30240544
TI  - Altered phenotypes via graft-transmitted siRNAs.

PMID- 30240543
TI  - Determining the minimal clinically important difference for the PEmbQoL
      questionnaire, a measure of pulmonary embolism-specific quality of life.
AB  - Essentials The minimal clinically important difference (MCID) for PEmbQoL has not
      yet been determined. We estimated the MCID for PEmbQoL and its subscales via
      anchor- and distribution-based approaches. Our results indicate that MCID for
      PEmbQoL appears to be 15 points. Our work enables interpretation of changes or
      differences in PEmbQoL. SUMMARY: Background Pulmonary embolism (PE) reduces
      quality of life (QOL). The PEmbQoL questionnaire, a PE-related QOL measure, was
      recently developed and validated and has been used to quantify disease-specific
      QOL in clinical studies of patients with PE. However, to date, interpretation of
      PEmbQoL scores has been limited by a lack of information on the minimal
      clinically important difference (MCID) of this measure. Objective To determine
      the MCID for PEmbQoL and its subscales using anchor-based and distribution-based
      approaches. Methods We analyzed data from the ELOPE Study, a prospective,
      multicenter cohort study of long-term outcomes after a first episode of acute PE.
      At baseline and 1, 3, 6 and 12 months after PE, we measured generic QOL (SF-36),
      PE-specific QOL (PEmbQoL) and dyspnea severity (UCSD Shortness of Breath
      Questionnaire). We used time-varying repeated-measures mixed-effect models to
      estimate anchor-based MCID and effect sizes to estimate distribution-based MCID.
      Results Eighty-two patients participated in this sub-study. Their mean age was
      49.4 years, 60% were male and 84% had PE diagnosed in an outpatient setting.
      Using both anchor- and distribution-based approaches, the MCID for PEmbQoL
      appears to be 15 points. Based on this MCID, 42%, 59%, 66% and 75% of patients
      experienced at least one MCID unit of improvement in PEmbQoL from baseline to 1,
      3, 6 and 12 months, respectively. Conclusion Our results provide new information
      on the MCID of PEmbQoL, a PE-specific QOL questionnaire that can be used by
      researchers and clinicians to measure and interpret changes in PE-specific QOL
      over time, or as an outcome in clinical trials.

PMID- 30240545
TI  - Clozapine as an early-stage treatment.

PMID- 30240546
TI  - The American College of Chest Physician score to assess the risk of bleeding
      during anticoagulation in patients with venous thromboembolism: comment.

PMID- 30240547
TI  - Human posterior parietal cortex responds to visual stimuli as early as
      peristriate occipital cortex.
AB  - Much of what is known about the timing of visual processing in the brain is
      inferred from intracranial studies in monkeys, with human data limited to mainly
      noninvasive methods with lower spatial resolution. Here, we estimated visual
      onset latencies from electrocorticographic (ECoG) recordings in a patient who was
      implanted with 112 subdural electrodes, distributed across the posterior cortex
      of the right hemisphere, for presurgical evaluation of intractable epilepsy.
      Functional MRI prior to surgery was used to determine boundaries of visual areas.
      The patient was presented with images of objects from several categories. Event
      related potentials (ERPs) were calculated across all categories excluding
      targets, and statistically reliable onset latencies were determined, using a
      bootstrapping procedure over the single trial baseline activity in individual
      electrodes. The distribution of onset latencies broadly reflected the known
      hierarchy of visual areas, with the earliest cortical responses in primary visual
      cortex, and higher areas showing later responses. A clear exception to this
      pattern was a robust, statistically reliable and spatially localized, very early
      response, on the bank of the posterior intraparietal sulcus (IPS). The response
      in the IPS started nearly simultaneously with responses detected in peristriate
      visual areas, around 60 ms poststimulus onset. Our results support the notion of
      early visual processing in the posterior parietal lobe, not respecting
      traditional hierarchies, and give direct evidence for onset times of visual
      responses across the human cortex.

PMID- 30240548
TI  - Identification of hepatotoxicity and renal dysfunction of pyrene in adult male
      rats.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic
      pollutants primarily formed from the incomplete combustion of carbonaceous
      materials, and have adverse effects on human health. In this study, we
      investigated whether pyrene, a PAH consisting of 4 fused benzene rings, has
      adverse effects on rat. Adult male Sprague-Dawly rats were treated daily by oral
      gavage with vehicle (corn oil) or pyrene at doses of 375, 750, 1500, or 2200
      mg/kg/day for 4 days. The results showed that pyrene caused hepatotoxicity in
      rats. When compared with the control group, relative liver weights, plasma
      alanine aminotransferase, and direct bilirubin levels significantly increased
      after pyrene exposure. Hepatocyte swelling and degeneration and decreased hepatic
      total glutathione (GSH) levels were also found in pyrene-exposed rats. We further
      observed that mRNA levels of several hepatic metabolizing enzymes regulated by
      constitutive androstane receptor (CAR) such as CYP2B1 and CYP2B2 significantly
      increased in pyrene-exposed rats. These results suggest that decreased GSH
      levels, elevated hepatic metabolizing enzyme gene expression, and CAR activation
      are important contributors for pyrene-induced hepatotoxicity in rats.
      Additionally, we found pyrene significantly induced plasma inflammatory indices
      including white blood cell and lymphocyte counts. We also observed that pyrene
      exposure increased relative weight of kidneys and disrupted kidney function with
      elevated urea and creatinine levels in rats.

PMID- 30240550
TI  - Antibody-Based Tracers for PET/SPECT Imaging of Chronic Inflammatory Diseases.
AB  - Chronic inflammatory diseases are often progressive, resulting not only in
      physical damage to patients but also social and economic burdens, making early
      diagnosis of them critical. Nuclear medicine techniques can enhance the detection
      of inflammation by providing functional as well as anatomical information when
      combined with other modalities such as magnetic resonance imaging, computed
      tomography or ultrasonography. Although small molecules and peptides were mainly
      used for the treatment and imaging of chronic inflammatory diseases in the past,
      antibodies and their fragments have also been emerging for chronic inflammatory
      diseases as they show high specificity to their targets and can have various
      biological half-lives depending on how they are engineered. In addition, imaging
      with antibodies or their fragments can visualize the in vivo biodistribution of
      the probes or help monitor therapeutic responses, thereby providing physicians
      with a greater understanding of drug behavior in vivo and another means of
      monitoring their patients. In this review, we introduce various targets and
      radiolabeled antibody-based probes for the molecular imaging of chronic
      inflammatory diseases in preclinical and clinical studies. Targets can be
      classified into three different categories: 1) cell-adhesion molecules, 2)
      surface markers on immune cells, and 3) cytokines or enzymes. The limitations and
      future directions of using radiolabeled antibodies for imaging inflammatory
      diseases are also discussed.

PMID- 30240551
TI  - [Oral health in asthmatic children using inhaled therapy. Study in the UTH of
      Casablanca].
AB  - Objective: The aim of the study was to investigate oral health in asthmatic
      children using inhaled therapy and to compare the oral health status according to
      beta2 agonist and corticosteroid dose administrated. Methods: The study group
      composed of 160 children aged between 2 and 15 years old who had bronchial asthma
      at different degrees of severity, the children followed at university hospital of
      Casablanca. A questionnaire was filled referring to oral health habits. For
      dental examinations, world health organization criteria and for plaque indices
      the Silness and Loe plaque index were used. Oral mucosal was examined to detect
      candidiasis or ulcerations. Results: The dental plaque registered was 1,13 +/-
      0,64. The mean DMFT was 3,75 +/- 1,53 and the mean DMFT was 5,50 +/- 3,02. A
      statistically significant higher average DMFT and DMFT values were observed with
      higher dose of beta2 agonist (p < 0,05). Almost a third of studied population had
      oral candidiasis and 6,9% had ulcerations. These oral mucosal lesions were
      particularly observed in children receiving inhaled corticosteroid higher than
      400 ug/j (P < 10-5) and they were lower in children using a spacer device and
      rinsing the mouth after treatment (P < 10-5). Conclusion: The results suggest
      higher caries susceptibility and oral mucosal lesions among asthmatic children
      undergoing inhaled treatment with beta2 agonist and corticosteroid. A special
      attention by doctors and health professionals of these patients is necessary and
      asthmatic children are recommended to adopt more precautionary oral hygiene
      practices.

PMID- 30240552
TI  - The prevalence, oral manifestations and management of viral hepatitis in Saudi
      Arabia: an update.
AB  - The aim of this review is to update healthcare professionals about the prevalence
      of various hepatitis viruses in the Saudi population. A perspective on the global
      and regional prevalence of hepatitis A, B and C viruses has also been given. The
      oral manifestations of hepatitis infection, the risks of patients and healthcare
      workers acquiring these infections, as well as the management of dental patients
      with hepatitis infection in the dental clinical setting has also been discussed.
      The universal precautions which should be observed while treating these patients
      have been reiterated, whereby detailed steps as pertaining to the management of
      these patients have been described, so as to optimize patient treatment, and at
      the same time to prevent dental healthcare workers from acquiring infection. The
      purpose of such management is therefore to ultimately improve the quality of life
      of patients infected with hepatitis viruses.

PMID- 30240553
TI  - [Epidemiology of maxillo-facial traumatism s sequels at stomatology and maxillo
      facial surgery service of Yalgado Ouedraogo University Hospital Center].
AB  - Introduction: Our study brings back the epidemiological and anatomo-clinical
      characteristics of the maxillo-facial traumatisms sequels at Yalgado Ouedraogo
      University Hospital Center of Ouagadougou. Methodology: It was a transversal
      descriptive study going from May 2013 to April 2015. Results and Discussion: In
      all, 152 cases of post traumatisms sequels were collected. The masculine sex was
      more affected with a sex-ratio of 2,53. The mean age was 30,80 years. The public
      road accidents (73,68%) were the main etiology of initial lesions. The isolated
      functional and morphological sequels respectively represented 1/3 and 1/6 of
      cases. Half of patients had mixed sequels.The odontological sequels (41,45%), the
      disgracious scars (93,68%), the neurological sequels (15,79%), the ocular sequels
      (11,18%), and the temporo-mandibular ankylosis were the main sequels found in our
      study.These sequels could be explained by the nature of initial lesions and the
      lateness of consultations. Conclusion: Development of population's awareness and
      close interdisciplinary collaboration helped to reduce the frequency of these
      sequels.

PMID- 30240554
TI  - [Treatment management of a case of class I bialveolar protrusion with mouth
      breathing].
AB  - This is the case of a 12-year-old African young girl with bialveolar protrusion
      and night mouth breathing. Orthodontic treatment without dental extraction
      consisted after tonsillectomy in retraction of anterior teeth in the diastema
      spaces. The normalization of the angle of the upper incisor has improved
      bialveolar protrusion without alteration to the prior balance of soft tissue.

PMID- 30240555
TI  - [Immediate full removable dentures. A clinical reality of oral medicine].
AB  - The decision to extract the last teeth represents for the patient an aesthetic,
      functional and moral damage. The realization of an immediate complete removable
      denture is indicated to remedy these difficulties. This will make it possible to
      ensure a rational and efficient management of this transition to total
      edentulous. The restorations of aesthetics and functions as well as patient
      comfort constitute the essential therapeutic objectives to be achieved and this
      thanks to the immediate denture.This work presents, through clinical cases, the
      indications and the management of four patients who have never worn a removable
      denture.

PMID- 30240556
TI  - [Interest of prosthodontic periodontal surgery in the success of anterior fixed
      prostheses].
AB  - Introduction: Periodontal prosthodontic surgery plays a major role in the
      integration of aesthetic and functional prosthetic restorations, including in the
      anterior area. Indeed, any dento-gingival disharmony of volume or shape must be
      corrected beforehand, thus justify a plastic periodontal surgery. Observation:
      This is a 20-year-old patient, who consulted for essentially aesthetic motive:
      the restoration of the fracture 11. Clinical examination revealed the presence of
      a defective provisional prosthesis on 11, an unsightly filling composite resin on
      the 21, asymmetry of the gingival contour, as well as a low located upper labial
      brake. Juxta-bone decay of the lingual wall of the 11 was prominent on the retro
      alveolar. Discussion: To meet the growing aesthetic demand of the patient, a
      multidisciplinary care was considered: a gingivectomy has been carried out, in
      order to align the collar of the 11 with that of the 21, associated with a
      coronal elongation landscaping biological space on the lingual side of the 11.
      And to optimize the therapeutic outcome, a frenectomy of the upper labial brake
      was performed.

PMID- 30240558
TI  - [Fortuitous discovery of a Stafne bone cavity in the Cone Beam CT sialography].
AB  - The Stafne defect is a benign, asymptomatic, non-progressive and rare bone
      depression, mainly discovered by chance in the posterior mandibular region. It is
      described radiographically as an oval radiolucency located below the mandibular
      canal, in the molar region, close to the submandibular gland.Sialography is a
      traditional technique in the radiographic examination of salivary glands that
      involves the injection of an iodine-based contrast medium into the main salivary
      duct. The Cone Beam Computed Tomography (CBCT) is a 3D imaging technique that has
      modernized the dental and maxillofacial practice with its advantages such as high
      speed, good spatial resolution and low radiation exposure. The CBCT Sialography
      that consists in a 3D Sialography with cone beam offers the same benefits as
      traditional sialography and allows three-dimensional viewing. It is a new imaging
      test for an accurate anatomical study of the major salivary glands and their
      relationships with their environments.The aim of this report is to present a case
      of Stafne bone cavity containing right submandibular gland tissue, occurring in a
      58-year-old man and diagnosed by using CBCT sialography.

PMID- 30240557
TI  - [Odontogenic myxoma of the maxilla: report of a case].
AB  - Myxoma is a rare variety of benign tumors of the jaw, whose origin is embryonic
      mesenchymal dental follicle.Clinical and radiological manifestations are variable
      and non-specific and can lend confusion with other lesions.We describe a case of
      very invasive odontogenic myxoma , observed in a woman of 51 years. Clinically,
      the patient had left maxillary swelling, painless, firm to the touch. CT facial
      bones showed an expansive osteolytic process blowing the jaw.The treatment
      consisted of a wide excision of the tumor by endobuccal way, the tumor is
      individualized well from the bone. Pathological examination of the surgical
      specimen was diagnosed odontogenic myxoma. The short-term trend has shown no
      clinical and radiological local recurrence.The diagnosis is based on clinical,
      radiological and histological. This tumor is locally aggressive, which can lead
      to significant facial deformities and dental disturbances. The recurrent nature
      of myxoma imposes a broad radical treatment beyond the limits of the lesion. The
      loss of important substance required surgical repair or prosthetic.

PMID- 30240559
TI  - Ebola haemorrhagic fever and Nigerian dental healthcare providers - knowledge of
      the disease.
AB  - Objective: The aim of this study was to assess the knowledge of Ebola
      Haemorrhagic fever (EHF) among the University of Benin clinical dental students.
      Methods: The study was a descriptive, cross-sectional study among consenting
      clinical (4th, 5th and 6th year) dental students of the University of Benin. The
      data collection tool was a 17-item self-administered validated questionnaire with
      a Chronbach's alpha value of 0.84. Data from the questionnaires were scored and
      graded, coded and finally entered into Statistical Package for Social Sciences
      (SPSS) version 21.0 for data analysis. All data collected were subjected to
      descriptive and inferential statistics to generate frequencies, percentages and
      Chi-square values at a significance of P < 0.05. Results: Out of the 79
      questionnaires distributed, 76 were returned duly filled, giving a response rate
      of 96.2%. The sample consisted of 67.1% male and 32.9% female clinical dental
      students, with a male to female ratio of approximately 2:1. About 89.5% of the
      respondents were in the 3rd decade of life. The average score for the
      participants was 11.34 +/- 2.20 which was above the average category. More than
      half (55.3%) of the clinical dental students had good knowledge. Over 98% of the
      students knew that EHF outbreaks occur primarily in Central and West Africa,
      however, only 16.7% of the students were aware that infected persons spread virus
      to others up to 7 weeks after recovery from illness. Conclusion: The clinical
      dental students easily identified EHF as a viral infection with the fruit bats as
      the natural host of the Ebola organisms. However, their knowledge of
      communicability and diagnostics was on the average. Proper knowledge regarding
      EHF and infection preventive measures can be the key to safety of the dentists
      and patients in the event of an EHF epidemic.

PMID- 30240560
TI  - [Ultrasound and X-ray-cholangiography diagnostic of Mirizzi syndrome].
AB  - Objective: To improve the results of preoperative diagnosis of Mirizzi syndrome.
      Material and Methods: Under our supervision for 2006-2015 we had 23 patients with
      the Mirizzi syndrome. Verification of cholecystolithiasis, condition of
      gallbladder's wall and biliary tract dilatation degree was evaluated
      sonographically. Biliary decompression was realised by percutaneous transhepatic
      cholangiostomy that was implemented under the combined ultrasonic and X-ray
      control by the Seldinger technique for self-locking pigtail drainages 8 F. As a
      method for direct visualization of the bile ducts was used antegrade
      cholangiography. Results: Preoperative diagnosis was verified in 18 (78.3%)
      patients, based on the results of ultrasound and data of antegrade
      cholangiography. In I type of Mirizzi syndrome (prefistule form) was revealed a
      combination of non-standard ultrasonic symptoms: if there were signs of "high"
      extrahepatic block of bile ducts (area of liver gate and confluence of hepatic
      ducts) there was recorded actual intravesical bile hypertension. Lack of
      lymphadenopathy near the choledoch and focal lesions of liver parenchyma in the
      goal area confirmed the benign character of the "high" bile ducts block. II type
      of Mirizzi syndrome (fistula form) was characterized by the presence of
      megacholelitiasis combined with a lack of intravesical bile hypertension.
      Antegrade cholangiography in combination with intra-ductal diagnostic catheters
      and manipulation wires and in some cases with cholecystography allowed to
      differentiate types of Mirizzi syndrome. In 5 cases Mirizzi syndrome was an
      intraoperative finding. Antegrade minimal-invasive access to the biliary tree was
      used in patients with high risk of surgery for subsequent X-ray interventions
      (lithotripsy, balloon dilatation of major duodenal papilla, dislocation of stones
      to the duodenum). Conclusions: Effective preoperative diagnosis of Mirizzi
      syndrome can be successful more than in half cases of the combined use of
      ultrasonography of the biliary tract and the results of antegrade dynamic
      cholangiography. That was carried out through percutaneous transhepatic
      cholangiostomy in conjunction with additional diagnostic intraluminal
      manipulations (wires and catheter inspection and palpation).

PMID- 30240561
TI  - Monte Carlo Simulation of Low-Count Signals in Time-of-Flight Mass Spectrometry
      and Its Application to Single-Particle Detection.
AB  - Many modern time-of-flight mass spectrometry (TOFMS) instruments use fast analog
      to-digital conversion (ADC) with high-speed digitizers to record mass spectra
      with extended dynamic range (compared to time-to-digital conversion). The
      extended dynamic range offered by ADC detection is critical for accurate
      measurement of transient events. However, the use of ADC also increases the
      variance of the measurements by sampling the gain statistics of electron
      multipliers (EMs) used for detection. The influence of gain statistics on the
      shape of TOF signal distributions is especially pronounced at low count rates and
      is a major contributor to measurement variance. Here, we use Monte Carlo methods
      to simulate low-ion-count TOFMS signals as a function of Poisson statistics and
      the measured pulse-height distribution (PHD) of the EM detection system. We find
      that a compound Poisson distribution calculated via Monte Carlo simulation
      effectively describes the shape of measured TOFMS signals. Additionally, we apply
      Monte Carlo simulation results to single-particle inductively coupled plasma (sp
      ICP) TOFMS analysis. We demonstrate that subtraction of modeled TOFMS signals can
      be used to quantitatively uncover particle-signal distributions buried beneath
      dissolved-signal backgrounds. On the basis of simulated signal distributions, we
      also calculate new critical values ( LC) that are used as decision thresholds for
      the detection of discrete particles. This new detection criterion better accounts
      for the shape of dissolved signal distributions and therefore provides more
      robust identification of single particles with ICP-TOFMS.

PMID- 30240562
TI  - Kinetic Strategies for the Formation of Graphyne Nanowires via Sonogashira
      Coupling on Ag(111).
AB  - The selection of a reaction pathway with high energy barrier in a multipath on
      surface reaction system has been challenging. Herein, we report the successful
      control of the reaction system of 1,1'-biphenyl-4-bromo-4'-ethynyl (BPBE) on
      Ag(111), in which three coupling reactions (Glaser, Ullman, Sonogashira) are
      involved. Either graphdiyne (GDY) or graphyne (GY) nanowires can be formed by
      distinct kinetic strategies. As the energetically favorable pathway, the
      formation of a GDY nanowire is achieved by hierarchical activation of Glaser
      (with lowest energy barrier) and Ullman coupling of BPBE. On the other hand, the
      formation of a GY nanowire originates from the high selectivity of the high
      barrier Sonogashira coupling, whose indispensable kinetic parameters are high
      surface temperature, low molecular coverage, and low precursor evaporation rate,
      as derived from a series of control experiments. This work achieves the
      fabrication of GY nanowires via on-surface Sonogashira coupling for the first
      time and reveals mechanistic control strategies for potential syntheses of other
      functional nanostructures via cross-couplings on surfaces.

PMID- 30240563
TI  - Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the
      Vesicular Monoamine Transporter.
AB  - Methamphetamine, a human vesicular monoamine transporter 2 (VMAT2) substrate,
      releases dopamine, serotonin, and norepinephrine from vesicles into the cytosol
      of presynaptic neurons and induces reverse transport by the monoamine
      transporters to increase extracellular neurotransmitters. Currently available
      radioligands for VMAT2 have considerable liabilities: The binding of
      [3H]dihydrotetrabenazine ([3H]DHTB) to a site on VMAT2 is not dependent on ATP,
      and [3H]reserpine binds almost irreversibly to VMAT2. Herein we demonstrate that
      several arylpiperidinylquinazolines (APQs) are potent inhibitors of [3H]reserpine
      binding at recombinant human VMAT2 expressed in HEK-293 cells. These compounds
      are biodiastereoselective and bioenantioselective. The lead radiolabeled APQ is
      unique because it binds reversibly to VMAT2 but does not bind the [3H]DHTB
      binding site. Furthermore, experimentation shows that several novel APQ ligands
      have high potency for inhibition of uptake by both HEK-VMAT2 cells and mouse
      striatal vesicles and may be useful tools for characterizing drug-induced effects
      on human VMAT2 expression and function.

PMID- 30240564
TI  - Quantifying Confidence in DFT-Predicted Surface Pourbaix Diagrams of Transition
      Metal Electrode-Electrolyte Interfaces.
AB  - Density functional theory (DFT) calculations have been widely used to predict the
      activity of catalysts based on the free energies of reaction intermediates. The
      incorporation of the state of the catalyst surface under the electrochemical
      operating conditions while constructing the free-energy diagram is crucial,
      without which even trends in activity predictions could be imprecisely captured.
      Surface Pourbaix diagrams indicate the surface state as a function of the pH and
      the potential. In this work, we utilize error-estimation capabilities within the
      Bayesian ensemble error functional with van der Waals correlations exchange
      correlation functional as an ensemble approach to propagate the uncertainty
      associated with the adsorption energetics in the construction of Pourbaix
      diagrams. Within this approach, surface-transition phase boundaries are no longer
      sharp and are therefore associated with a finite width. We determine the surface
      phase diagram for several transition metals under reaction conditions and
      electrode potentials relevant for the oxygen reduction reaction. We observe that
      our surface phase predictions for most predominant species are in good agreement
      with cyclic voltammetry experiments and prior DFT studies. We use the OH*
      intermediate for comparing adsorption characteristics on Pt(111), Pt(100),
      Pd(111), Ir(111), Rh(111), and Ru(0001) since it has been shown to have a higher
      prediction efficiency relative to O*, and find the trend Ru > Rh > Ir > Pt > Pd
      for (111) metal facets, where Ru binds OH* the strongest. We robustly predict the
      likely surface phase as a function of reaction conditions by associating
      confidence values for quantifying the confidence in predictions within the
      Pourbaix diagram. We define a confidence quantifying metric, using which certain
      experimentally observed surface phases and peak assignments can be better
      rationalized. The probabilistic approach enables a more accurate determination of
      the surface structure and can readily be incorporated in computational studies
      for better understanding the catalyst surface under operating conditions.

PMID- 30240565
TI  - Differentiating Antibiotic-Resistant Staphylococcus aureus Using Secondary
      Electrospray Ionization Tandem Mass Spectrometry.
AB  - Secondary electrospray ionization mass spectrometry (SESI-MS) is an innovative
      metabolomics approach that primarily focuses on the gas-phase analyte detection.
      In this study, we developed a secondary electrospray ionization tandem mass
      spectrometry (SESI-MS/MS) method with a homemade SESI-MS front end, for
      sensitive, reproducible and selective detection of headspace volatile organic
      compounds (VOCs) emitted from bacterial culture. The optimized SESI-MS/MS was
      applied to examine the VOC metabolome of a pair of isogenic methicillin
      susceptible and resistant Staphylococcus aureus (MSSA and MRSA) strains. From the
      headspace of bacterial culture, twelve organic acids, and eight amino acids with
      the mass range of 40-300 Da were specifically targeted with two selected reaction
      monitoring (SRM) transitions. Our results indicated that MSSA and MRSA strains
      can be clearly differentiated via partial least-squares discriminant analysis
      (PLS-DA) based on their headspace metabolic profiles. Furthermore, we studied the
      stress response of MSSA and MRSA to antibiotics treatment. Our result showed that
      MSSA and MRSA generated dramatically changed VOC metabolic profiles in response
      to ampicillin, which indicated that SESI-MS/MS could also be used for antibiotic
      treatment response monitoring in future studies. This study showed that SESI
      MS/MS VOC analysis provides an additional approach to the bacterial metabolome
      detection complementary to traditional aqueous phase metabolite analysis. To the
      best of our knowledge, this was the first time that SESI-MS/MS was applied to
      investigate the bacterial metabolic perturbations caused by antibiotic treatment.

PMID- 30240566
TI  - Optimization and Application of Paper-Based Spray Ionization Mass Spectrometry
      for Analysis of Natural Organic Matter.
AB  - In this study, paper-based ionization techniques-paper spray ionization (PSI) and
      paper spray chemical ionization (PSCI)-were evaluated and applied for high
      resolution mass spectrometry (MS)-based analysis of natural organic matter (NOM).
      Methanol:isopropyl alcohol (50:50, v/v) and ethanol emerged as good spray
      solvents for PSI, and hexane:dichloromethane (50:50, v/v) was a good spray
      solvent for PSCI. PSI-MS spectra could be obtained with NOM samples on the
      microgram scale, which is a critical advantage over conventional electrospray
      ionization (ESI)-MS when the amount of available sample is limited. In addition,
      PSI is more tolerant to salt contamination than ESI for NOM analysis. PSCI
      preferentially ionized less polar compounds, which may not be ionized well using
      ESI. Therefore, PSCI can be used as a complementary method to ESI or PSI.
      Comparison of the numbers of peaks obtained with ESI-, PSI-, and PSCI-MS showed
      that employing PSI and PSCI can increase the number of compounds that can be
      detected by high-resolution MS. In conclusion, the data presented in this study
      showed that PSI and PSCI are suitable ionization techniques for NOM analysis. To
      the best of our knowledge, this is the first study evaluating and applying PSI
      and PSCI for NOM analysis.

PMID- 30240567
TI  - Hydrocapacitor for Harvesting and Storing Energy from Water Movement.
AB  - Based on porous carbon nanotube/polyaniline composite (CNT/PANI) and poly(vinyl
      alcohol) gel, we fabricated centimeter-sized hydrocapacitors with dual functions
      of energy conversion and storage with an efficient low-cost method. Owning to
      excellent hydrophily and large specific capacitance of CNT/PANI, the
      hydrocapacitors can easily convert energy from water movement induced by
      capillarity, gravity, or air pressure difference into electricity and store the
      generated electricity. Especially, sandwich-like hydrocapacitors outputted large
      current of 1.65 mA through an external load of 100 Omega, and hydrocapacitors
      showed good extendibility by connecting in series. To explain the mechanism of
      hydrocapacitors in this work, a possible model based on capillarity and
      traditional streaming potential was proposed and discussed. Hydrocapacitors here
      also provide a reference for future integration of nanogenerators and energy
      storage parts.

PMID- 30240568
TI  - Resting metabolic rate in muscular physique athletes: validity of existing
      methods and development of new prediction equations.
AB  - Estimation of resting metabolic rate (RMR) is an important step for prescribing
      an individual's energy intake. The purpose of this study was to evaluate the
      validity of portable indirect calorimeters and RMR prediction equations in
      muscular physique athletes. Twenty-seven males (n=17; BMI: 28.8+/-2.0
      kg/m<sup>2</sup>; body fat: 12.5+/-2.7%) and females (n=10; BMI: 22.8+/-1.6
      kg/m<sup>2</sup>; body fat: 19.2+/-3.4%) were evaluated. The reference RMR value
      was obtained from the ParvoMedics TrueOne(r) 2400 indirect calorimeter, and the
      Cosmed Fitmate<sup>TM</sup> and Breezing(r) Metabolism Tracker provided
      additional RMR estimates. Existing RMR prediction equations based on body weight
      (BW) or dual-energy x-ray absorptiometry (DXA) fat-free mass (FFM) were also
      evaluated. Errors in RMR estimates were assessed using validity statistics,
      including t-tests with Bonferroni correction, linear regression, and calculation
      of the SEE, total error, and 95% limits of agreement. Additionally, new
      prediction equations based on BW (RMR [kcal/d] = 24.8*BW [kg] + 10) and FFM (RMR
      [kcal/d] = 25.9*FFM [kg] + 284) were developed using stepwise linear regression
      and evaluated using leave-one-out cross-validation. Nearly all existing BW- and
      FFM-based prediction equations, as well as the Breezing(r) Tracker, did not
      exhibit acceptable validity and typically underestimated RMR. The ten Haaf (2014)
      and Cunningham (1980) FFM-based equations may produce acceptable RMR estimates,
      although the Cosmed Fitmate<sup>TM</sup> and newly developed BW- and FFM-based
      equations may be most suitable for RMR estimation in male and female physique
      athletes. Future research should provide additional external cross-validation of
      the newly-developed equations in order to refine the ability to predict RMR in
      physique athletes.

PMID- 30240570
TI  - National Food Affordability: A County-Level Analysis.
AB  - The purpose of this study was to explore the sociodemographic factors that
      contribute to food affordability across space, with specific emphasis on rural
      and urban differences in the United States. A regression analysis was used to
      predict food affordability from several predictors in rural and urban areas, with
      a subanalysis of Appalachian and Delta counties. Rural households had
      significantly higher food expenditures to income ratios compared with urban
      counties; Appalachian and Delta counties had the highest on average food
      expenditure to income ratio. Affordable food buffers vulnerable families against
      food insecurity and subsequent chronic health issues, which are especially
      relevant in the Appalachian and Delta counties.

PMID- 30240571
TI  - Examining Variation in Life Expectancy Estimates by ZIP Code Tabulation Area
      (ZCTA) in Hawaii's Four Main Counties, 2008-2012.

PMID- 30240572
TI  - Increasing prevalence and dissemination of invasive nontyphoidal Salmonella
      serotype Typhimurium with multidrug resistance in hospitalized patients from
      southern Brazil.
AB  - INTRODUCTION: Nontyphoidal Salmonella serotypes are the main cause of human food
      borne infection, including several hospitalization cases in the developing
      countries. AIM: To detect the main serotypes and to characterize the antibiotic
      resistance of human non-enteric and enteric nontyphoidal Salmonella from clinical
      isolates in Brazil. METHODS: Salmonella serotypes were identified by
      microbiological and molecular methods. Susceptibility testing to antibiotics was
      performed by agar disk diffusion. Real-time PCRs were carried out for the
      detection of the genus Salmonella as well as serotypes Typhimurium and
      Enteritidis. RESULTS: A total of 307 nontyphoidal Salmonella were isolated from
      289 different patients in a reference laboratory (LACEN-RS) from Southern Brazil
      in a six-year period (2010-2015). There were 45 isolates from emerging cases and
      244 from sporadic cases in hospitalized patients. Non-enteric isolates were
      detected in 42.6% of the patients from sources such as urine, blood and other
      clinical fluids. Serological and PCR-specific tests demonstrated that Typhimurium
      (48.4%) and Enteritidis (18.3%) were the most frequent serotypes. Typhimurium
      isolates were generally resistant to three or more antibiotic classes, while
      Enteritidis isolates to one or two classes. Typhimurium was the most frequent
      serotype in all samples (48.4%), mainly among the hospitalized patients (55.6%),
      and presented the highest rates of multidrug resistance (59.3% of the isolates of
      this serotype). Further, the prevalence of this serotype increased along the
      years of the study in comparison to other nontyphoidal Salmonella serotypes.
      CONCLUSION: Greater public health attention should be given to prevent
      salmonellosis in the community and in hospital settings to reduce the rates of
      Typhimurium strains with multidrug resistance.

PMID- 30240573
TI  - First record of Culex (Culex) bidens (Diptera: Culicidae) in Colombia: Taxonomic
      and epidemiological implications.
AB  - Arbovirus transmission cycles must be studied locally since both vectors and
      hosts vary in different regions. Colombia has a highly diverse mosquito fauna.
      Culex (Culex) bidens is reported here for the first time in Colombia. Because Cx.
      bidens Dyar and Knab and Cx. declarator Dyar and Knab share a close taxonomic
      history and because it is difficult to differentiate between them, a
      morphological and molecular comparison was performed. The male genitalia of three
      specimens of Cx. bidens from Colombia were mounted on microscope slides and
      morphologically compared with the male genitalia of Cx. declarator also from
      Colombia. In Cx. bidens, the individual teeth of the lateral plate are long,
      straight, laterally directed and sharply pointed; in Cx. declarator these teeth
      are robust, curved, with convex margins and bluntly rounded. Moreover, DNA was
      extracted from the same specimens and a fragment of the cytochrome c oxidase
      subunit I mitochondrial gene was amplified and sequenced. Neither Cx. bidens nor
      Cx. declarator were clustered in the Neighbour-joining topology, with K2P
      interspecific divergence between 0.15-1.45%. The circulation of Eastern Equine
      Encephalitis Virus in Colombia was reported since 1957 and Cx. bidens was
      suspected to be the vector of this virus during an epizootic in Argentina in
      1988. Hybridization between species of the subgenus Culex has been demonstrated,
      hence the degree of reproductive isolation between Cx. bidens and Cx. declarator
      should be investigated, as well as their taxonomic status, because they only can
      be discriminated by a single male genitalic feature and not by nuclear or
      mitochondrial markers.

PMID- 30240574
TI  - Progress and future challenges in aging and diversity research in the United
      States.
AB  - In 2016, the UC Davis Latino Aging Research Resource Center and UC Davis
      Alzheimer's Disease Center brought together experts from across the country to
      consolidate current knowledge and identify future directions in aging and
      diversity research. This report disseminates the research priorities that emerged
      from this conference, building on an earlier Gerontological Society of America
      preconference. We review key racial/ethnic differences in cognitive aging and
      dementia and identify current knowledge gaps in the field. We advocate for a
      systems-level framework for future research whereby environmental, sociocultural,
      behavioral, neuropathological, genetic, and psychometric levels of analysis are
      examined together to identify pathways and mechanisms that influence disparities.
      We then discuss steps to increase the recruitment and retention of racial/ethnic
      minorities in aging studies, as none of the recommendations will be possible
      without strong collaboration between racial/ethnic minority communities and
      researchers. This approach is consistent with the National Institute on Aging
      Health Disparities framework.

PMID- 30240575
TI  - Genetic overlap between vascular pathologies and Alzheimer's dementia and
      potential causal mechanisms.
AB  - INTRODUCTION: We sought to examine the genetic overlap between vascular
      pathologies and Alzheimer's disease (AD) dementia, and the potential mediating
      role of vascular pathologies between AD-related genetic variants and late-life
      cognition. METHODS: For 2907 stroke-free older individuals, we examined the
      association of polygenic risk scores for AD dementia (ADPRSs) with vascular
      pathologies and with cognition. Mediation analyses addressed whether association
      between ADPRSs and cognition was mediated by a vascular pathology. RESULTS:
      ADPRSs were associated with lobar cerebral microbleeds, white matter lesion load,
      and coronary artery calcification, mostly explained by single nucleotide
      polymorphisms in the 19q13 region. The effect of ADPRSs on cognition was
      partially but significantly mediated by cerebral microbleeds, white matter
      lesions, and coronary artery calcification. DISCUSSION: Our findings provide
      evidence for genetic overlap, mostly due to apolipoprotein E (APOE), between
      vascular pathologies and AD dementia. The association between AD polygenic risk
      and late-life cognition is mediated in part via effects on vascular pathologies.

PMID- 30240577
TI  - Computational mechanisms in genetic regulation by RNA.
AB  - The evolution of the genome has led to very sophisticated and complex regulation.
      Because of the abundance of non-coding RNA (ncRNA) in the cell, different species
      will promiscuously associate with each other, suggesting collective dynamics
      similar to artificial neural networks. A simple mechanism is proposed allowing
      ncRNA to perform computations equivalent to neural network algorithms such as
      Boltzmann machines and the Hopfield model. The quantities analogous to the neural
      couplings are the equilibrium constants between different RNA species. The
      relatively rapid equilibration of RNA binding and unbinding is regulated by a
      slower process that degrades and creates new RNA. The model requires that the
      creation rate for each species be an increasing function of the ratio of total to
      unbound RNA. Similar mechanisms have already been found to exist experimentally
      for ncRNA regulation. With the overall concentration of RNA regulated,
      equilibrium constants can be chosen to store many different patterns, or many
      different input-output relations. The network is also quite insensitive to random
      mutations in equilibrium constants. Therefore one expects that this kind of
      mechanism will have a much higher mutation rate than ones typically regarded as
      being under evolutionary constraint.

PMID- 30240576
TI  - Potential of recombinant 2-Cys peroxiredoxin protein as a vaccine for Fasciola
      gigantica infection.
AB  - Helminth 2-cys peroxiredoxin (Prx) is a major antioxidant enzyme that protects
      parasites against hydrogen peroxide-generating oxidative stress from the hosts'
      immune responses. This enzyme has been found in all stages of the tropical liver
      fluke, Fasciola gigantica. To investigate the potential of the recombinant F.
      gigantica Prx-2 (rFgPrx-2) as a vaccine candidate, vaccine trials in mice were
      carried out. In this study, the ICR mice were immunized with rFgPrx-2 combined
      with Freund's adjuvant and infected with F. gigantica metacercariae. The vaccine
      efficacy was estimated by quantitate fluke recovery, antibody levels and liver
      function. The protection by rFgPrx-2 against F. gigantica infection was achieved
      at 43-46% compared with adjuvant-infected and non-immunized-infected control
      groups, respectively. The vaccine elicited both Th1 and Th2 humoral immune
      responses with predominance of Th2 as indicated by the higher level of IgG1 in
      sera of immunized mice. However, the levels of liver damage markers, serum
      glutamate oxalic transaminase (SGOT) and serum glutamic pyruvate transaminase
      (SGPT) in rFgPrx-2 immunized group did not show significant difference in
      comparison with the controls. This study suggested that rFgPrx-2 may have a
      potential as a vaccine against tropical fasciolosis.

PMID- 30240578
TI  - Self-sustaining positive feedback loops in discrete and continuous systems.
AB  - We consider a dynamic framework frequently used to model gene regulatory and
      signal transduction networks: monotonic ODEs that are composed of Hill functions.
      We derive conditions under which activity or inactivity in one system variable
      induces and sustains activity or inactivity in another. Cycles of such influences
      correspond to positive feedback loops that are self-sustaining and control
      robust, in the sense that these feedback loops "trap" the system in a region of
      state space from which it cannot exit, even if the other system variables are
      externally controlled. To demonstrate the utility of this result, we consider
      prototypical examples of bistability and hysteresis in gene regulatory networks,
      and analyze a T-cell signal transduction ODE model from the literature.

PMID- 30240579
TI  - Modelling skin wound healing angiogenesis: A review.
AB  - The occurrence of wounds is a main health concern in Western society due to their
      high frequency and treatment cost. During wound healing, the formation of a
      functional blood vessel network through angiogenesis is an essential process.
      Angiogenesis allows the reestablishment of the normal blood flow, the sufficient
      exchange of oxygen and nutrients and the removal of metabolic waste, necessary
      for cell proliferation and viability. Mathematical and computational models
      provide new tools to improve the healing process. In fact, over the last thirty
      years, in silico models have been continuously formulated to describe the effect
      of several biological and mechanical factors in angiogenesis during wound
      healing. Additionally, with different levels of complexity, these models allow
      coupling the human skin structure, to distinct cell types and growth factors, to
      study extracellular matrix composition and to understand its deformation. This
      paper discusses how in silico models, which are more economical and less time
      consuming comparatively to laboratory methodologies, can help test new strategies
      to promote/optimize angiogenesis. The continuum, cell-based and hybrid
      mathematical models of wound healing angiogenesis are reviewed in the present
      paper, in order to identify possible improvements. Accordingly, the development
      of higher dimension models incorporating multiscale analysis at molecular,
      cellular and tissue level remains a challenge that future models should consider.

PMID- 30240581
TI  - Chronic methamphetamine self-administration dysregulates 5-HT2A and mGlu2
      receptor expression in the rat prefrontal and perirhinal cortex: Comparison to
      chronic phencyclidine and MK-801.
AB  - Chronic methamphetamine (meth) abuse often turns into a compulsive drug-taking
      disorder accompanied by persistent cognitive deficits and re-occurring psychosis.
      Possible common neurobiological substrates underlying meth-induced deficits and
      schizophrenia remain poorly understood. Serotonin 2A (5-HT2A) and metabotropic
      glutamate 2 (mGlu2) receptors co-regulate psychosis-like behaviors and cognitive
      function in animals. Therefore, in the present study we examined the effects of
      chronic exposure to three different drugs known to produce persistent deficits in
      sensorimotor gating and cognition [meth, phencyclidine (PCP) and MK-801] on the
      expression of 5-HT2A and mGlu2 within the rat medial prefrontal cortex (mPFC),
      dorsal hippocampus (dHPC) and perirhinal cortex (PRh). Adult male rats underwent
      14 days of: (a) meth self-administration (6 h/day), (b) phencyclidine (PCP; 5
      mg/kg, twice/day) administration, or (c) MK-801 (0.3 mg/kg, twice/day)
      administration. Seven days after the discontinuation of drug administration,
      tissues of interest were collected for protein expression analysis. We found that
      despite different pharmacological mechanism of action, chronic meth, PCP, and MK
      801 similarly dysregulated 5-HT2A and mGlu2, as indicated by an increase in the 5
      HT2A/mGlu2 expression ratio in the mPFC (all three tested drugs), PRh (meth and
      PCP), and dHPC (MK-801 only). Complementary changes in G-protein expression
      (increase in Galphaq and decrease in Galphai) were also observed in the mPFC of
      meth animals. Finally, we found that 5-HT2A/mGlu2 cooperation can be mediated in
      part by the formation of the receptor heteromer in some, but not all cortical
      regions. In summary, these data suggest that a shift towards increased
      availability (and G-protein coupling) of cortical 5-HT2A vs. mGlu2 receptors may
      represent a common neurobiological mechanism underlying the emergence of
      psychosis and cognitive deficits observed in subjects with meth use disorder and
      schizophrenia.

PMID- 30240580
TI  - Role of p62/SQSTM1 in lipopolysaccharide (LPS)-induced mucus hypersecretion in
      bronchial epithelial cells.
AB  - AIMS: The aims of this study were to evaluate the effects of p62/SQSTM1
      expression levels on lipopolysaccharide (LPS)-induced mucus secretion in BEAS-2B
      bronchial epithelial cells by measuring expression levels of the MUC5AC gene and
      the Mucin-5AC (MUC5AC) protein. MATERIALS AND METHODS: Bronchial epithelial
      cells, BEAS-2B, were treated with LPS at different time points. Rapamycin, an
      autophagy agonist, was added to the BEAS-2B cells 30 min before LPS treatment.
      Lentivirus transfection was then used to knock down the expression of p62/SQSTM1
      (Sequestosome 1) to investigate changes in the downstream signaling pathway.
      Western blotting and immunofluorescence were used to study the expression levels
      of MUC5AC, and reverse transcription-polymerase chain reaction (RT-PCR) was used
      to study the expression of MUC5AC mRNA. KEY FINDINGS: LPS treatment of BEAS-2B
      cells inhibited autophagy, activated the nuclear factor kappa B (NF-kappaB)
      signaling pathway and increased the expression of MUC5AC. The autophagy agonist,
      rapamycin, activated autophagy, inhibited the NF-kappaB signaling pathway and
      decreased LPS-induced expression of MUC5AC. Knockdown of p62/SQSTM1 expression
      reduced activation of the NF-kappaB signaling pathway and reduced LPS-induced
      mucus secretion by BEAS-2B cells in vitro. SIGNIFICANCE: In this in vitro study,
      which utilized BEAS-2B bronchial epithelial cells, p62/SQSTM1 was shown to have a
      role in LPS-induced mucus hypersecretion by activating the NF-kappaB signaling
      pathway.

PMID- 30240582
TI  - Infection with the multi-host micro-parasite Apicystis bombi (Apicomplexa:
      Neogregarinorida) decreases survival of the solitary bee Osmia bicornis.
AB  - The micro-parasites present in the Apidae pollinator community are mostly multi
      host pathogens. To study the impact of these multi-host pathogens on the Apidae
      pollinator community, as a driver of wild bee decline, pathological studies are
      needed for different hosts. Yet data on the pathogenesis of these pathogens for
      different genera and species is scarce or lacking, especially for solitary bee
      species. In this study, we monitored the effect of the multi-host micro-parasite
      Apicystis bombi on the lifespan of Osmia bicornis, a common solitary bee. Our
      results show that A. bombi infection significantly reduces O. bicornis survival.

PMID- 30240583
TI  - Using the fungus Arthrobotrys cladodes var. macroides as a sustainable strategy
      to reduce numbers of infective larvae of bovine gastrointestinal parasitic
      nematodes.
AB  - Research in the area of sanitation in ruminant production has focused on
      discovery of potential agents for biological control of helminths with
      nematophagous fungi and has provided evidence of success. The antagonistic
      potential of the fungus Arthrobotrys cladodes var. macroides on infective larvae
      of bovine gastrointestinal parasitic nematodes was evaluated by scanning electron
      microscopy. Additionally, an in vivo test of the resistance to digestive
      processes and viability of the fungus was carried out using a formulation based
      on sodium alginate administered orally in cattle. Production of conidia and
      chlamydospores was high. In in vitro tests, the number of infective nematode
      larvae was reduced 68.7% by the fungus in the treated group compared to the
      control group. The interaction between the fungus and the nematodes was confirmed
      by scanning electron microscopy. Plates containing fecal samples collected after
      oral administration of 100 g of pellets containing the A. cladodes fungus showed
      that the fungus survived passage through the gastrointestinal tract of ruminants,
      grew on agar, formed traps and preyed on L3 larvae of gastrointestinal parasites.
      The results of the present study provide a new opportunity for alternative,
      environmentally safe control of ruminant nematodes.

PMID- 30240585
TI  - Inhibition of interleukin-6 trans-signaling prevents inflammation and endothelial
      barrier disruption in retinal endothelial cells.
AB  - Vascular inflammation plays a critical role in the pathogenesis of diabetic
      retinopathy. Recently, Interleukin-6 (IL-6) trans-signaling via soluble IL-6
      receptor (sIL-6R) has emerged as a prominent regulator of inflammation in
      endothelial cells. This study was designed to test the hypothesis that selective
      inhibition of the IL-6 trans-signaling pathway will attenuate inflammation and
      subsequent barrier disruption in retinal endothelial cells. Human retinal
      endothelial cells (HRECs) were exposed to IL-6 and sIL-6R to induce IL-6 trans
      signaling and the commercially available compound sgp130Fc (soluble gp-130 fused
      chimera) was used to selectively inhibit IL-6 trans-signaling. IL-6 trans
      signaling activation caused a significant increase in STAT3 phosphorylation,
      expression of adhesion molecules, ROS production and apoptosis in HRECs whereas a
      significant decrease in mitochondrial membrane potential and NO production was
      observed in IL-6 trans-signaling activated cells. These changes were not observed
      in cells pre-treated with sgp130Fc. IL-6 trans-signaling activation was
      sufficient to cause barrier disruption in endothelial monolayers and pre
      treatment of HRECs with sgp130Fc, maintained endothelial barrier function similar
      to that of untreated cells. Thus, in conclusion, these results indicate that IL-6
      trans-signaling is an important mediator of inflammation, apoptosis and barrier
      disruptive effects in the retinal endothelial cells and inhibition of the IL-6
      trans-signaling pathway using sgp130-Fc attenuates vascular inflammation and
      endothelial barrier disruption.

PMID- 30240584
TI  - Dopaminergic amacrine cell number, plexus density, and dopamine content in the
      mouse retina: Strain differences and effects of Bax gene disruption.
AB  - Many types of retinal neuron modulate the distribution of their processes to
      ensure a uniform coverage of the retinal surface. Dendritic field area, for
      instance, is inversely related to the variation in cellular density for many cell
      types, observed either across retinal eccentricity or between different strains
      of mice that differ in cell number. Dopaminergic amacrine (DA) cells, by
      contrast, have dendritic arbors that bear no spatial relationship to the presence
      of their immediate homotypic neighbors, yet it remains to be determined whether
      their coverage upon the retina, as a population, is conserved across variation in
      their total number. The present study assessed the overall density of the
      dopaminergic plexus in the inner plexiform layer in the presence of large
      variation in the total number of DA cells, as well as their retinal dopamine
      content, to determine whether either of these features is conserved. We first
      compared these traits between two strains of mice (C57BL/6J and A/J) that exhibit
      a two-fold difference in DA cell number. We subsequently examined these same
      traits in littermate mice for which the pro-apoptotic Bax gene was either intact
      or knocked out, yielding a five-fold difference in DA cell number. In both
      comparisons, we found greater plexus density and DA content in the strain or
      condition with the greater number of DA cells. The population of DA cells,
      therefore, does not appear to self-regulate its process coverage to achieve a
      constant density as the DA mosaic is established during development, nor its
      functional dopamine content in maturity.

PMID- 30240586
TI  - Methodological development and biological observations of cell free DNA with a
      simple direct fluorescent assay in colorectal cancer.
AB  - BACKGROUND: Cell free DNA (cfDNA) has shown promising utility as prognostic
      biomarker for patients with colorectal cancer (CRC), with an ongoing need to
      optimize and validate the laboratory methodology. Here, we report our
      optimization and validation of a direct fluorescent assay and display the
      potential utility in patients with colorectal cancer. METHODS: Plasma cfDNA was
      analyzed by a direct fluorescent assay (DFA) and compared to quantification by
      droplet digital PCR (ddPCR). For clinical validation, baseline blood samples were
      available for a total of 273 patients from six different Nordic trials, covering
      patients with locally advanced rectal cancer (n = 176, cohorts A + B), liver
      limited metastatic CRC (n = 75C + D) and wide spread metastatic CRC (n = 22 E +
      F). RESULTS: Validating the DFA analysis with ddPCR revealed a strong correlation
      with an R2 of 0.81. For the clinical cohorts, the levels of cfDNA were: 0.8 ng/uL
      (95%CI 0.75-0.83) (A + B), 0.93 ng/uL (95%CI 0.86-1.02) (C + D) and 1.2 ng/uL
      (95%CI 0.85-1.47) (E + F), respectively (p < 0.01). All cohorts of colorectal
      cancer had higher levels of cell free DNA than healthy individuals (n = 94) (p <
      0.01). CONCLUSION: Analysis of cell free DNA by a direct fluorescent assay could
      be an attractive laboratory option for a rapid inexpensive quantification of cell
      free DNA.

PMID- 30240587
TI  - RNA interference to enhance radiation therapy: Targeting the DNA damage response.
AB  - RNA interference (RNAi) therapy is an emerging class of biopharmaceutical that
      has immense potential in cancer medicine. RNAi medicines are based on synthetic
      oligonucleotides that can suppress a target protein in tumour cells with high
      specificity. This review explores the attractive prospect of using RNAi as a
      radiosensitiser by targeting the DNA damage response. There are a multitude of
      molecular targets involved in the detection and repair of DNA damage that are
      suitable for this purpose. Recent developments in delivery technologies such
      nanoparticle carriers and conjugation strategies have allowed RNAi therapeutics
      to enter clinical trials in the treatment of cancer. With further progress, RNAi
      targeting of the DNA damage response may hold great promise in guiding radiation
      oncology into the era of precision medicine.

PMID- 30240588
TI  - Stroma-induced phenotypic plasticity offers phenotype-specific targeting to
      improve melanoma treatment.
AB  - Cancer cells' phenotypic plasticity, promoted by stromal cells, contributes to
      intra-tumoral heterogeneity and affects response to therapy. We have disclosed an
      association between fibroblast-stimulated phenotype switching and resistance to
      the clinically used BRAF inhibitor (BRAFi) vemurafenib in malignant melanoma,
      revealing a challenge in targeting the fibroblast-induced phenotype. Here we
      compared molecular features and drug sensitivity in melanoma cells grown as co
      cultures with fibroblasts versus mono-cultures. In the presence of fibroblasts,
      melanoma cells switched to the dedifferentiated, mesenchymal-like, inflammatory
      phenotype that showed reduced sensitivity to the most of 275 tested cancer drugs.
      Fibroblasts, however, sensitized melanoma cells to PI3K inhibitors (PI3Ki) and
      particularly the inhibitor of GSK3, AR-A014418 (GSK3i), that showed superior
      efficacy in co-cultures. The proteome changes induced by the BRAFi + GSK3i
      combination mimicked changes induced by BRAFi in mono-cultures, and GSK3i in co
      cultures. This suggests that the single drug drives the response to the
      combination treatment, depending on fibroblast presence or absence, consequently,
      phenotype. We propose that the BRAFi and GSK3i (or PI3Ki) combination exemplifies
      phenotype-specific combinatorial treatment that should be beneficial in
      phenotypically heterogeneous tumors rich in stromal interactions.

PMID- 30240589
TI  - Glutamate-Glutamine Transfer and Chronic Stress-Induced Sex Differences in
      Cocaine Responses.
AB  - Substance use disorders (SUD) often co-occur with other mental disorders such as
      major depression (MD). Our previous findings revealed sex-dependent changes in
      extracellular levels of glutamate (Glu) and glutamine (Gln) in the nucleus
      accumbens (NAc) in Long-Evans rats that were exposed to 21 days of chronic social
      defeat stress (CSDS), which models MD. The current study investigated the role of
      a Gln transporter called sodium-coupled neutral amino acid transporter subtype
      1/2 (SNAT 1/2), phosphate-activated glutaminase (PAG), and astrocytic glutamate
      transporter-1 (GLT-1) on CSDS animals exposed to cocaine. Before cocaine
      exposure, CSDS males already showed decreased levels of SNAT 1/2 in the NAc and
      prefrontal cortex (PFC) compared to non-CSDS controls. The reduction in SNAT 1/2
      levels was associated with an increase in Gln localization in the mitochondrial
      outer membrane in accumbal glutamatergic nerve terminals projecting from the PFC.
      CSDS females showed increased GLT-1 levels in the NAc and PFC compared to non
      CSDS controls. Both acute and repeated cocaine exposure attenuated locomotor
      responses in CSDS males but increased those in CSDS females. Cocaine reduced SNAT
      1/2 levels in the NAc but increased them in the PFC in CSDS males. Additionally,
      both PAG and GLT-1 levels were increased in the PFC in CSDS males. On the other
      hand, cocaine reduced SNAT 1/2 and GLT-1 levels in the NAc and PFC in CSDS
      females. Our results show that CSDS altered locomotor responses upon cocaine
      exposure in a sex-dependent manner that may be mediated by molecules associated
      with the Glu-Gln transfer.

PMID- 30240590
TI  - Role of NADPH oxidase in cooperative reactive oxygen species generation in
      dopaminergic neurons induced by combined treatment with dieldrin and lindane.
AB  - Environmental exposure to the highly persistent chlorinated pesticides including
      dieldrin and lindane is postulated to be a risk factor to the development of
      Parkinson's disease, a devastating movement disorder. We have previously reported
      that the combined treatment with dieldrin and lindane induces a cooperative
      toxicity in the rat N27 dopaminergic neuronal cells through increased oxidative
      stress and mitochondrial dysfunction. In this study, we investigated the
      involvement of NADPH oxidase (NOX) proteins in the combined treatment with
      dieldrin and lindane-induced dopaminergic neurotoxicity. Immunoblot analysis
      demonstrated the presence of NADPH Oxidase 1 (Nox1) isoform and p67phox in N27
      neurons. Furthermore, treatment with dieldrin and lindane upregulated the
      cellular expression of Nox1 but not p67phox protein. Functionally, dieldrin and
      lindane-induced ROS production was attenuated, in a dose-dependent manner, by Nox
      inhibitors diphenylene iodonium and apocynin. Subcellular localization analysis
      of Nox1 and p67phox proteins indicated colocalization of both subunits with
      mitochondria in untreated cells. Treatment with dieldrin and lindane further
      increased mitochondrial colocalization of Nox1 protein, suggesting a potentially
      prominent role for mitochondrial Nox1 protein in dieldrin and lindane-induced ROS
      generation in dopaminergic neurons and its contribution to the combined
      organochlorinated pesticide-induced neurotoxicity.

PMID- 30240591
TI  - Towards high-throughput fast photochemical oxidation of proteins: Quantifying
      exposure in high fluence microtiter plate photolysis.
AB  - Protein structural analysis by mass spectrometry has gained significant
      popularity in recent years, including high-resolution protein topographical
      mapping by fast photochemical oxidation of proteins (FPOP). The ability to
      provide protein topographical information at moderate spatial resolution makes
      FPOP an attractive technology for the protein pharmaceutical discovery and
      development processes. However, current technology limits the throughput and
      requires significant manual sample manipulation. Similarly, as FPOP is being used
      on larger samples, sample flow through the capillary becomes challenging. No
      systematic comparison of the performance of static flash photolysis with
      traditional flow FPOP has been reported. Here, we evaluate a 96-well microtiter
      based laser flash photolysis method for the topographical probing of proteins,
      which subsequently could be used to analyze higher order structure of the protein
      in a high-throughput fashion with minimal manual sample manipulation. We used
      multiple metrics to compare microtiter FPOP performance with that of traditional
      flow FPOP: adenine-based hydroxyl radical dosimetry, oxidation efficiency of a
      model peptide, and hydroxyl radical protein footprint of myoglobin. In all cases,
      microtiter plate FPOP performed comparably with traditional flow FPOP, requiring
      a small fraction of the time for exposure. This greatly reduced sample exposure
      time, coupled with automated sample handling in 96-well microtiter plates, makes
      microtiter-based FPOP an important step in achieving the throughput required to
      adapt hydroxyl radical protein footprinting for screening purposes.

PMID- 30240592
TI  - Propionic acid metabolism and poly-3-hydroxybutyrate-co-3-hydroxyvalerate
      production by a prpC mutant of Herbaspirillum seropedicae Z69.
AB  - Polyhydroxyalkanoates (PHAs) are thermoplastic polyesters produced by a wide
      range of bacteria as carbon and energy reserves. PHA accumulation is typically
      increased under unbalanced growth conditions and with carbon source in excess.
      Although polyhydroxybutyrate (PHB) could be used for specific applications, it is
      brittle and not a useful alternative for plastics like polypropylene. Far more
      useful polypropylene-like PHAs, are copolymers composed of 3-hydroxybutyrate and
      3-hydroxyvalerate, P(3HB-co-3HV). Propionic acid is one of the carbon sources
      that can be used to generate 3HV. A mutant derived from Herbaspirillum
      seropedicae Z69, a strain previously described as capable of producing P(3HB-co
      3HV) from propionic acid, was constructed to increase 3HV biosynthetic
      efficiency. The strategy involved elimination of a catabolic route for propionyl
      CoA by deficiency marker exchange of a selected gene. The mutant (Z69Prp) was
      constructed by elimination of the 2-methylcitrate synthase (PrpC) gene of the 2
      methylcitrate cycle for propionate catabolism. Strain Z69Prp was unable to grow
      on sodium propionate, but in cultures with glucose-propionate accumulated 50% of
      its dry weight as copolymer. Z69Prp had 14.1 mol% 3HV; greater than that of
      strain Z69 (2.89 mol%). The 3HV yield from propionic acid (Y3HV/prop) was 0.80 g
      g-1, and below the maximum theoretical value (1.35 g g-1).

PMID- 30240593
TI  - Effectiveness of Exercise Interventions for Pain Reduction in People With
      Multiple Sclerosis: A Systematic Review and Meta-analysis of Randomized
      Controlled Trials.
AB  - OBJECTIVE: To systematically review the evidence of the effect of exercise
      compared with passive control on pain in people with multiple sclerosis. DATA
      SOURCE AND STUDY SELECTION: Five electronic databases were searched for
      randomized controlled trials published up to March 2017 that recruited people
      with multiple sclerosis where exercise was the intervention and pain was an
      outcome (PROSPERO registration number CRD42017060489). STATISTICAL ANALYSIS: A
      random-effects meta-analysis was conducted to estimate the standardized mean
      difference of the effect of exercise on pain between treatment and control
      groups. We assessed risk of bias, fitted meta-regression models to explore
      heterogeneity between studies, and assessed small study effects. DATA SYNTHESIS:
      Ten studies met the inclusion criteria (total sample size=389), and all studies
      were at high risk of bias. We found that exercise interventions were associated
      with less pain compared with passive control groups (standardized mean
      difference=-.46; 95% CI, -.92 to .00). There was high between-study heterogeneity
      (I2=77.0%), which was not explained by the prespecified study characteristics.
      There was also some evidence of small study effects. CONCLUSION: This is the
      first systematic review of the effect of exercise interventions on pain in people
      with multiple sclerosis, a chronic neurological disorder that affects 2.5 million
      people. We found some evidence that exercise compared with passive control
      alleviates pain in this population, but there were limitations in reporting and
      study quality with high risk of bias of individual studies and heterogeneity
      between studies.

PMID- 30240594
TI  - Benchmarks of significant change after aphasia rehabilitation.
AB  - OBJECTIVE: To establish benchmarks of significant change for aphasia
      rehabilitation outcome measures (i.e., Western Aphasia Battery-Aphasia Quotient
      [WAB-AQ], Communicative Effectiveness Index [CETI], Boston Naming Test [BNT]) and
      assess if those benchmarks significantly differed across subgroups (i.e., time
      post onset, dose frequency, treatment type). DATA SOURCES: A comprehensive
      literature search of 12 databases, reference lists of previous reviews, and
      evidence-based practice materials was conducted. STUDY SELECTION: Randomized
      controlled trials, quasi-experimental studies, single-subject design, and case
      studies that used a standardized outcome measure to assess change were included.
      Titles and full-text articles were screened using a dual review process. 78
      studies met criteria for inclusion. DATA EXTRACTION: Data were extracted
      independently and 25% of extractions were checked for reliability. All included
      studies were assigned quality indicator ratings and an evidence level. DATA
      SYNTHESIS: Random-effects meta-analyses were conducted separately for each study
      design group (i.e., within/between group comparisons). For within group designs,
      the summary effect size after aphasia rehabilitation was 5.03 points (95%
      confidence interval: 3.95-6.10, p < .001) on the WAB-AQ, 10.37 points (6.08
      14.66, p < .001) on the CETI and 3.30 points (2.43-4.18, p < .001) on the BNT.
      For between group designs, the summary effect size was 5.05 points (1.64-8.46, p
      = .004) on the WAB-AQ, and .55 points (-1.33, 2.43, p = .564) on the BNT, the
      latter of which was not significant. Subgroup analyses for the within group
      designs showed no significant differences in the summary effect size as a
      function of dose frequency, or treatment type. CONCLUSIONS: This study
      established benchmarks of significant change on three standardized outcome
      measures used in aphasia rehabilitation.

PMID- 30240595
TI  - SR-B1 involvement in keratinocytes in vitro wound closure.
AB  - Skin represents the most extended organ of human body, having as main function
      the protection of our body from outdoor stressors. Its protective ability is
      compromised when the skin is disrupted as a consequence of mechanical insults.
      For this purpose, cutaneous tissue is equipped with an efficient and fine
      mechanism involved in repairing the wounded area. Among the numerous players that
      take part in the wound healing process, SR-B1 has been recently shown to have a
      role in keratinocyte re-epithelialization. SR-B1 is a mediator of cholesterol
      uptake from HDLs, whereas it is implicated in other cellular processes such as
      vitamins absorption, vesicle trafficking or pathogen identification. The aim of
      this study was to investigate the mechanisms involved in SR-B1 role in skin wound
      closure. Our in vitro data demonstrated that SR-B1 influenced keratinocyte
      proliferation and migration through a downregulation of nuclear cyclin D1 levels
      and active MMP9 expression respectively possibly in an NF-kB-dependent mechanism.
      In addition, SR-B1 was also able to modulate keratinocyte morphology into a pro
      migratory cytoskeleton rearrangement. The present in vitro study suggests a new
      role of SRB1 as a possible new key player in cutaneous wound healing mechanism.

PMID- 30240597
TI  - This Month in AJP.
AB  - The following highlights summarize research articles that are published in the
      current issue of The American Journal of Pathology.

PMID- 30240596
TI  - Autophagy-Based Diagnosis of Pregnancy Hypertension and Pre-Eclampsia.
AB  - This commentary highlights the article by Aoki et al that shows that Atg7
      deficiency-mediated placental autophagy imbalance may contribute towards pre
      eclampsia.

PMID- 30240598
TI  - Small molecule-mediated reprogramming of human hepatocytes into bipotent
      progenitor cells.
AB  - BACKGROUND & AIMS: Currently, much effort is directed towards the development of
      new cell sources for clinical therapy using cell fate conversion by small
      molecules. Direct lineage reprogramming to a progenitor state has been reported
      in terminally differentiated rodent hepatocytes, yet remains a challenge in human
      hepatocytes. METHODS: Human hepatocytes were isolated from healthy and diseased
      donor livers and reprogrammed into progenitor cells by 2 small molecules, A83-01
      and CHIR99021 (AC), in the presence of EGF and HGF. The stemness properties of
      human chemically derived hepatic progenitors (hCdHs) were tested by standard in
      vitro and in vivo assays and transcriptome profiling. RESULTS: We developed a
      robust culture system for generating hCdHs with therapeutic potential. The use of
      HGF proved to be an essential determinant of the fate conversion process. Based
      on functional evidence, activation of the HGF/MET signal transduction system
      collaborated with A83-01 and CHIR99021 to allow a rapid expansion of progenitor
      cells through the activation of the ERK pathway. hCdHs expressed hepatic
      progenitor markers and could self-renew for at least 10 passages while retaining
      a normal karyotype and potential to differentiate into functional hepatocytes and
      biliary epithelial cells in vitro. Gene expression profiling using RNAseq
      confirmed the transcriptional reprogramming of hCdHs towards a progenitor state
      and the suppression of mature hepatocyte transcripts. Upon intrasplenic
      transplantation in several models of therapeutic liver repopulation, hCdHs
      effectively repopulated the damaged parenchyma. CONCLUSION: Our study is the
      first report of successful reprogramming of human hepatocytes to a population of
      proliferating bipotent cells with regenerative potential. hCdHs may provide a
      novel tool that permits expansion and genetic manipulation of patient-specific
      progenitors to study regeneration and the repair of diseased livers. LAY SUMMARY:
      Human primary hepatocytes were reprogrammed towards hepatic progenitor cells by a
      combined treatment with 2 small molecules, A83-01 and CHIR99021, and HGF.
      Chemically derived hepatic progenitors exhibited a high proliferation potential
      and the ability to differentiate into hepatocytes and biliary epithelial cells
      both in vitro and in vivo. This approach enables the generation of patient
      specific hepatic progenitors and provides a platform for personal and stem cell
      based regenerative medicine.

PMID- 30240599
TI  - Proton Beam Therapy for Ameloblastic Carcinoma of the Maxilla: Report of a Rare
      Case.
AB  - Ameloblastic carcinoma (AC) is a rare malignant odontogenic tumor that combines
      the histologic features of ameloblastoma with those of cytologic atypia. The
      standard treatment for this lesion is wide local excision. Proton beam therapy
      (PBT) can deliver high irradiation doses to the target and avoid irradiation to
      surrounding normal tissues, but no reports of PBT for AC have been published thus
      far. This report describes the case of a 70-year-old woman with a pathologic
      diagnosis of maxillary AC who refused surgical resection and received
      hypofractionated PBT at a total dose of 69 Gy in 23 fractions. She has been alive
      for more than 5 years after PBT without any evidence of recurrence and side
      effects. This is the first reported case of successful treatment after curative
      radiation therapy for maxillary AC.

PMID- 30240600
TI  - A review of biological and pharmacological activities of Baccharis trimera.
AB  - Plant-based systems continue to play an essential role in healthcare, and their
      use by different cultures has been extensively documented. Baccharis trimera,
      popularly known as carqueja, is a plant widely distributed in South America and
      has been traditionally used for treating several diseases particularly associated
      with hepatic and gastric disorders. The present study aimed to provide a general
      review of the available literature on phytochemical and biological data related
      to the species B. trimera as a potential source of new compounds with biological
      activity. Considering phytochemical studies, flavonoids, terpenes and chlorogenic
      acids were the main classes of compounds identified in aerial parts which were
      correlated with their biological activities such as antioxidant, anti
      inflammatory, gastric and hepatic-protector, anti-microbial, anti-fungal, anti
      parasitic and aid in weight loss.

PMID- 30240601
TI  - Secondary metabolites overproduction through transcriptional gene cluster
      refactoring.
AB  - We present a random rational approach enabling the construction of overproducing
      strains in two steps. The approach first involves creating a library of clusters
      of interest, in which native promoters are substituted with randomly generated
      constitutive synthetic promoters, and then expressing this library in an
      appropriate host strain. This strategy is fast, easy to use, accounts for the
      architecture of a cluster and completely decouples the expression of a gene
      cluster from complex native regulatory networks. The strategy was applied to
      improve the production of a macrocyclic peptide, bottromycin, which possesses
      antibacterial activity against multidrug-resistant bacteria and is a blueprint
      for a new class of antibacterials. We successfully optimized the expression of
      genes in operons and created several variants of the bottromycin gene cluster
      that provide 5-50 fold higher titres of bottromycin than the natural one, thus
      resulting in the identification of several new bottromycin derivatives not
      previously described. Moreover, due to the higher bottromycin yield, bottromycin
      derivatization was performed via the biosynthetic engineering of the gene
      cluster. The abovementioned features make this generic strategy a promising tool
      for the overproduction of known secondary metabolites and the activation of
      silent secondary metabolites in Actinobacteria.

PMID- 30240602
TI  - CVID enteropathy is characterized by exceeding low mucosal IgA levels and
      interferon-driven inflammation possibly related to the presence of a pathobiont.
AB  - Common variable immunodeficiency (CVID), the most common symptomatic primary
      antibody deficiency, is accompanied in some patients by a duodenal inflammation
      and malabsorption syndrome known as CVID enteropathy (E-CVID).The goal of this
      study was to investigate the immunological abnormalities in CVID patients that
      lead to enteropathy as well as the contribution of intestinal microbiota to this
      process.We found that, in contrast to noE-CVID patients (without enteropathy), E
      CVID patients have exceedingly low levels of IgA in duodenal tissues. In
      addition, using transkingdom network analysis of the duodenal microbiome, we
      identified Acinetobacter baumannii as a candidate pathobiont in E-CVID. Finally,
      we found that E-CVID patients exhibit a pronounced activation of immune genes and
      down-regulation of epithelial lipid metabolism genes. We conclude that in the
      virtual absence of mucosal IgA, pathobionts such as A. baumannii, may induce
      inflammation that re-directs intestinal molecular pathways from lipid metabolism
      to immune processes responsible for enteropathy.

PMID- 30240603
TI  - Coupling of DNA Replication and Negative Feedback Controls Gene Expression for
      Cell-Fate Decisions.
AB  - Cellular decision-making arises from the expression of genes along a regulatory
      cascade, which leads to a choice between distinct phenotypic states. DNA dosage
      variations, often introduced by replication, can significantly affect gene
      expression to ultimately bias decision outcomes. The bacteriophage lambda system
      has long served as a paradigm for cell-fate determination, yet the effect of DNA
      replication remains largely unknown. Here, through single-cell studies and
      mathematical modeling we show that DNA replication drastically boosts cI
      expression to allow lysogenic commitment by providing more templates. Conversely,
      expression of CII, the upstream regulator of cI, is surprisingly robust to DNA
      replication due to the negative autoregulation of the Cro repressor. Our study
      exemplifies how living organisms can not only utilize DNA replication for gene
      expression control but also implement mechanisms such as negative feedback to
      allow the expression of certain genes to be robust to dosage changes resulting
      from DNA replication.

PMID- 30240604
TI  - Olefination of Alkyl Halides with Aldehydes by Merging Visible-Light Photoredox
      Catalysis and Organophosphorus Chemistry.
AB  - Carbon-carbon double bond (C=C) formation is a crucial transformation in organic
      chemistry. Visible-light photoredox catalysis provides economical and sustainable
      opportunities for the development of novel and peculiar organic reactions. Here
      we report a method for the olefination of alkyl halides with aldehydes by visible
      light photoredox catalysis using triphenylphosphine as a reductive quencher (103
      examples). This transformation accommodates a variety of aldehydes including
      paraformaldehyde; aqueous formaldehyde; 2,2,2-trifluoroacetaldehyde monohydrate;
      2,2,2-trifluoro-1-methoxyethanol; and other common aldehydes. The present method
      exhibits several advantages, including operational simplicity, mild reaction
      conditions, wide functional group tolerance, and amenability to gram-scale
      synthesis. We anticipate that it will be widely used in the synthesis of organic
      molecules, natural products, biological molecules, and polymers.

PMID- 30240606
TI  - High-Energy-Level Blue Phosphor for Solution-Processed White Organic Light
      Emitting Diodes with Efficiency Comparable to Fluorescent Tubes.
AB  - A high-energy-level blue phosphor FIr-p-OC8 has been developed for solution
      processed white organic light-emitting diodes (WOLEDs) with comparable
      fluorescent tube efficiency. Benefiting from the electron-donating nature of the
      introduced alkoxy, FIr-p-OC8 shows not only efficient blue light but also
      elevated highest occupied molecular orbital/lowest unoccupied molecular orbital
      levels to well match the dendritic host H2. Consequently, the hole scattering
      between FIr-p-OC8 and H2 can be prevented to favor the direct exciton formation
      on the blue phosphor, leading to reduced driving voltage and thus improved power
      efficiency. By exploiting this approach, a maximum power efficiency of 68.5 lm W
      1 is achieved for FIr-p-OC8-based white devices, slightly declining to 47.0 lm W
      1 at a practical luminance of 1,000 cd m-2. This efficiency can be further raised
      to 96.3 lm W-1 @ 1,000 cd m-2 when a half-sphere is applied to increase light out
      coupling. We believe that our results can compete with commercial fluorescent
      tubes, representing an important progress in solution-processed WOLEDs.

PMID- 30240605
TI  - Local Oxidative Damage in the Soma and Dendrites Quarantines Neuronal
      Mitochondria at the Site of Insult.
AB  - Neurons are highly dependent on mitochondria, but little is known about how they
      react to a local mitochondrial oxidative insult. We therefore developed a
      protocol in primary hippocampal cultures that combines the photosensitizer mito
      KillerRed with fluorescent biosensors and photoactivatable GFP. We found in both
      the soma and dendrites that neurons restrict the local increase in mitochondria
      derived reactive oxygen species and the decrease in ATP production to the damaged
      compartment, by quarantining mitochondria. Although the cytosol of both the soma
      and dendrites became oxidized after mito-KillerRed activation, dendrites were
      more sensitive to the oxidative insult. Importantly, the impaired mitochondria
      exhibited decreased motility and fusion, thereby avoiding the spread of oxidation
      throughout the neuron. These results establish how neurons manage oxidative
      damage and increase our understanding about the somatodendritic regulation of
      mitochondrial functions after a local oxidative insult.

PMID- 30240607
TI  - Understanding How Wnt Influences Destruction Complex Activity and beta-Catenin
      Dynamics.
AB  - Despite extensive research on the canonical Wnt signaling pathway, the mechanism
      by which this signal downregulates the activity of destruction complexes and
      inhibits beta-catenin degradation remains controversial. In particular, recent
      attention has focused on two main competing mechanisms-inhibition of
      phosphorylation and inhibition of ubiquitination. Our combined experimental and
      theoretical analysis demonstrates that the disassembly of a fraction of the
      intracellular destruction complexes results in the partial inhibition of both
      beta-catenin phosphorylation and ubiquitination. This inhibition is spatially
      patterned, consistent with the relocalization of some destruction complexes to
      the cellular membrane upon Wnt stimulation. Moreover, in contrast to the
      generally accepted view that the destruction complex is highly processive, our
      analysis supports a distributive model, in which beta-catenin can dissociate from
      the complex between sequential phosphorylation events. Understanding the
      fundamental mechanism by which Wnt signaling is regulated provides a rational
      basis for tuning the pathway for scientific and therapeutic purposes.

PMID- 30240608
TI  - Soluble Abeta Oligomers Impair Dipolar Heterodendritic Plasticity by Activation
      of mGluR in the Hippocampal CA1 Region.
AB  - Soluble Abeta oligomers (oAbetas) contribute importantly to synaptotoxicity in
      Alzheimer disease (AD), but the mechanisms related to heterogeneity of synaptic
      functions at local circuits remain elusive. Nearly all studies of the effects of
      oAbetas on hippocampal synaptic plasticity have only examined homosynaptic
      plasticity. Here we stimulated the Schaffer collaterals and then simultaneously
      recorded in stratum radiatum (apical dendrites) and stratum oriens (basal
      dendrites) of CA1 neurons. We found that the apical dendrites are significantly
      more vulnerable to oAbeta-mediated synaptic dysfunction: the heterosynaptic basal
      dendritic long-term potentiation (LTP) remained unchanged, whereas the
      homosynaptic apical LTP was impaired. However, the heterosynaptic basal dendritic
      plasticity induced by either spaced 10-Hz bursts or low-frequency (1-Hz)
      stimulation was disrupted by oAbetas in a mGluR5-dependent manner. These results
      suggest that different firing patterns in the same neurons may be selectively
      altered by soluble oAbetas in an early phase of AD, before frank
      neurodegeneration.

PMID- 30240610
TI  - ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone
      Digesting Osteoclasts.
AB  - Bone-resorbing osteoclasts play a central role in bone remodeling and its
      pathology. To digest bone, osteoclasts re-organize both F-actin, to assemble
      podosomes/sealing zones, and membrane traffic, to form bone-facing ruffled
      borders enriched in lysosomal membrane proteins. It remains elusive how these
      processes are coordinated. Here, we show that ARAP1 (ArfGAP with RhoGAP domain,
      ankyrin repeat and PH domain-containing protein 1) fulfills this function. At
      podosomes/sealing zones, ARAP1 is part of a protein complex where its RhoGAP
      domain regulates actin dynamics. At endosomes, ARAP1 interacts with AP-3 adaptor
      complexes where its Arf-GAP domain regulates the Arf1-dependent AP-3 binding to
      membranes and, consequently lysosomal membrane protein transport to ruffled
      borders. Accordingly, ARAP1 or AP-3 depletion in osteoclasts alters their
      capacity to digest bone in vitro. and AP-3delta-deficient mocha mice, a model of
      the Hermansky-Pudlak storage pool syndrome, develop osteoporosis. Thus, ARAP1
      bridges F-actin and membrane dynamics in osteoclasts for proper bone homeostasis.

PMID- 30240609
TI  - Advances in Cathode Materials for High-Performance Lithium-Sulfur Batteries.
AB  - Lithium-sulfur batteries (LSBs) represent a promising energy storage technology,
      and they show potential for next-generation high-energy systems due to their high
      specific capacity, abundant constitutive resources, non-toxicity, low cost, and
      environment friendliness. Unlike their ubiquitous lithium-ion battery
      counterparts, the application of LSBs is challenged by several obstacles,
      including short cycling life, limited sulfur loading, and severe shuttling effect
      of polysulfides. To make LSBs a viable technology, it is very important to design
      and synthesize outstanding cathode materials with novel structures and
      properties. In this review, we summarize recent progress in designs,
      preparations, structures, and properties of cathode materials for LSBs,
      emphasizing binary, ternary, and quaternary sulfur-based composite materials. We
      especially highlight the utilization of carbons to construct sulfur-based
      composite materials in this exciting field. An extensive discussion of the
      emerging challenges and possible future research directions for cathode materials
      for LSBs is provided.

PMID- 30240611
TI  - Sodium Ion Capacitor Using Pseudocapacitive Layered Ferric Vanadate Nanosheets
      Cathode.
AB  - Sodium ion capacitors (SICs) are designed to deliver both high energy and power
      densities at low cost. Electric double-layer capacitive cathodes are typically
      used in these devices, but they lead to very limited capacity. Herein, we apply a
      pseudocapacitive layered ferric vanadate (Fe-V-O) as cathode to construct non
      aqueous SICs with both high energy and power densities. The Fe-V-O nanosheets
      cathode displays remarkable rate capability and cycling stability. The
      pseudocapacitive sodium storage mechanism of Fe-V-O, with over 83% of total
      capacity from capacitive contribution, is confirmed by kinetics analysis and ex
      situ characterizations. The capacitive-adsorption mechanism of hard carbon (HC)
      anode is demonstrated, and it delivers excellent rate capability. Based on as
      synthesized materials, the assembled HC//Fe-V-O SIC delivers a maximum energy
      density of 194 Wh kg-1 and power density of 3,942 W kg-1. Our work highlights the
      advantages of pseudocapacitive cathodes for achieving both high energy and power
      densities in sodium storage devices.

PMID- 30240612
TI  - Nck1 Deficiency Impairs Adipogenesis by Activation of PDGFRalpha in
      Preadipocytes.
AB  - Obesity results from an excessive expansion of white adipose tissue (WAT), which
      is still poorly understood from an etiologic-mechanistic perspective. Here, we
      report that Nck1, a Src homology domain-containing adaptor, is upregulated during
      WAT expansion and in vitro adipogenesis. In agreement, Nck1 mRNA correlates
      positively with peroxisome proliferator-activated receptor (PPAR) gamma and
      adiponectin mRNAs in the WAT of obese humans, whereas Nck1-deficient mice display
      smaller WAT depots with reduced number of adipocyte precursors and accumulation
      of extracellular matrix. Furthermore, silencing Nck1 in 3T3-L1 preadipocytes
      increases the proliferation and expression of genes encoding collagen, whereas it
      decreases the expression of adipogenic markers and impairs adipogenesis.
      Silencing Nck1 in 3T3-L1 preadipocytes also promotes the expression of platelet
      derived growth factor (PDGF)-A and platelet-derived growth factor receptor
      (PDGFR) alpha activation and signaling. Preventing PDGFRalpha activation using
      imatinib, or through PDGF-A or PDGFRalpha deficiency, inhibits collagen
      expression in Nck1-deficient preadipocytes. Finally, imatinib rescues
      differentiation of Nck1-deficient preadipocytes. Altogether, our findings reveal
      that Nck1 modulates WAT development through PDGFRalpha-dependent remodeling of
      preadipocytes.

PMID- 30240613
TI  - CRISPR/Cas9-based Genome Editing in Pseudomonas aeruginosa and Cytidine Deaminase
      Mediated Base Editing in Pseudomonas Species.
AB  - Pseudomonas species are a large class of gram-negative bacteria that exhibit
      significant biomedical, ecological, and industrial importance. Despite the
      extensive research and wide applications, genetic manipulation in Pseudomonas
      species, in particular in the major human pathogen Pseudomonas aeruginosa,
      remains a laborious endeavor. Here we report the development of a genome editing
      method pCasPA/pACRISPR by harnessing the CRISPR/Cas9 and the phage lambda-Red
      recombination systems. The method allows for efficient and scarless genetic
      manipulation in P. aeruginosa. By engineering the fusion of the cytidine
      deaminase APOBEC1 and the Cas9 nickase, we further develop a base editing system
      pnCasPA-BEC, which enables highly efficient gene inactivation and point mutations
      in a variety of Pseudomonas species, such as P. aeruginosa, Pseudomonas putida,
      Pseudomonas fluorescens, and Pseudomonas syringae. Application of the two genome
      editing methods will dramatically accelerate a wide variety of investigations,
      such as bacterial physiology study, drug target exploration, and metabolic
      engineering.

PMID- 30240614
TI  - Genome Architecture Mediates Transcriptional Control of Human Myogenic
      Reprogramming.
AB  - Genome architecture has emerged as a critical element of transcriptional
      regulation, although its role in the control of cell identity is not well
      understood. Here we use transcription factor (TF)-mediated reprogramming to
      examine the interplay between genome architecture and transcriptional programs
      that transition cells into the myogenic identity. We recently developed new
      methods for evaluating the topological features of genome architecture based on
      network centrality. Through integrated analysis of these features of genome
      architecture and transcriptome dynamics during myogenic reprogramming of human
      fibroblasts we find that significant architectural reorganization precedes
      activation of a myogenic transcriptional program. This interplay sets the stage
      for a critical transition observed at several genomic scales reflecting
      definitive adoption of the myogenic phenotype. Subsequently, TFs within the
      myogenic transcriptional program participate in entrainment of biological
      rhythms. These findings reveal a role for topological features of genome
      architecture in the initiation of transcriptional programs during TF-mediated
      human cellular reprogramming.

PMID- 30240616
TI  - Isotopic Evidence for Disrupted Copper Metabolism in Amyotrophic Lateral
      Sclerosis.
AB  - Redox-active metals are thought to be implicated in neurodegenerative diseases
      including amyotrophic lateral sclerosis (ALS). To address this point, we measured
      the concentrations of 12 elements and, for the first time, the stable isotope
      compositions of copper (redox-active) and zinc (redox-inactive) in human
      cerebrospinal fluids of 31 patients with ALS, 11 age-matched controls (CTRL), and
      14 patients with Alzheimer disease. We first show that metal concentrations
      weakly discriminate patients with ALS from the two other groups. We then report
      that zinc isotopic compositions are similar in the three groups, but that
      patients with ALS have significantly 65copper-enriched isotopic compositions
      relative to CTRL and patients with AD. This result unambiguously demonstrates
      that copper is implicated in ALS. We suggest that this copper isotopic signature
      may result from abnormal protein aggregation in the brain parenchyma, and propose
      that isotopic analysis is a potential tool that may help unraveling the molecular
      mechanisms at work in ALS.

PMID- 30240615
TI  - DNA, RNA, and Protein Tools for Editing the Genetic Information in Human Cells.
AB  - Solving the structure of DNA in 1953 has unleashed a tour de force in molecular
      biology that has illuminated how the genetic information stored in DNA is copied
      and flows downstream into RNA and proteins. Currently, increasingly powerful
      technologies permit not only reading and writing DNA in vitro but also editing
      the genetic instructions in cells from virtually any organism. Editing specific
      genomic sequences in living cells has been particularly accelerated with the
      introduction of programmable RNA-guided nucleases (RGNs) based on prokaryotic
      CRISPR adaptive immune systems. The repair of chromosomal breaks made by RGNs
      with donor DNA patches results in targeted genome editing involving the
      introduction of specific genetic changes at predefined genomic positions. Hence,
      donor DNAs, guide RNAs, and nuclease proteins, each representing the molecular
      entities underlying the storage, transmission, and expression of genetic
      information, are, once delivered into cells, put to work as agents of change of
      that very same genetic text. Here, after providing an outline of the programmable
      nuclease-assisted genome editing field, we review the increasingly diverse range
      of DNA, RNA, and protein components (e.g., nucleases and "nickases") that, when
      brought together, underlie RGN-based genome editing in eukaryotic cells.

PMID- 30240617
TI  - Room Temperature Processing of Inorganic Perovskite Films to Enable Flexible
      Solar Cells.
AB  - Inorganic lead halide perovskite materials have attracted great attention
      recently due to their potential for greater thermal stability compared with
      hybrid organic perovskites. However, the high processing temperature to convert
      from the non-perovskite phase to the cubic perovskite phase in many of these
      systems has limited their application in flexible optoelectronic devices. Here,
      we report a room temperature processed inorganic perovskite solar cell (PSC)
      based on CsPbI2Br as the light harvesting layer. By combining this composition
      with key precursor solvents, we show that inorganic perovskite films can be
      prepared by the vacuum-assist method under room temperature conditions in air.
      Unencapsulated devices achieved power conversion efficiency up to 8.67% when
      measured under 1-sun irradiation. Exploiting this room temperature process,
      flexible inorganic PSCs based on an inorganic metal halide perovskite material
      are demonstrated.

PMID- 30240618
TI  - Visualizing Ligand Binding to a GPCR In Vivo Using NanoBRET.
AB  - The therapeutic action of a drug depends on its ability to engage with its
      molecular target in vivo. However, current drug discovery strategies quantify
      drug levels within organs rather than determining the binding of drugs directly
      to their specific molecular targets in vivo. This is a particular problem for
      assessing the therapeutic potential of drugs that target malignant tumors where
      access and binding may be impaired by disrupted vasculature and local hypoxia.
      Here we have used triple-negative human breast cancer cells expressing beta2
      adrenoceptors tagged with the bioluminescence protein NanoLuc to provide a
      bioluminescence resonance energy transfer approach to directly quantify ligand
      binding to a G protein-coupled receptor in vivo using a mouse model of breast
      cancer.

PMID- 30240619
TI  - Nanostructured Three-Dimensional Percolative Channels for Separation of Oil-in
      Water Emulsions.
AB  - Separation of oil/water mixtures has been one of the leading green technologies
      for applications such as oil recovery and water purification. Conventional
      methods to separate oil from water are based on phase separation via physical
      settlement or distillation. However, challenges still remain in the effective
      extraction of micron-sized oil droplets dispersed in water, in which case gravity
      fails to work as separating force. Here, we conformably decorate porous titanium
      (average pore size 30 MUm) with superhydrophilic nanotubes. The resulting three
      dimensional superhydrophilic micro channels thus provide a driving force for oil
      water separation at the nanotube/emulsion interface, enhancing significantly the
      water infiltration rate. The high efficiency (>99.95%, with oil droplets of
      average diameter 10 MUm) and strong mechanical durability make the structure a
      reusable oil/water separator. Our findings pave the way for future applications
      of oil-in-water emulsion separation, which can be readily scaled up for massive
      demulsification.

PMID- 30240620
TI  - Impaired Circadian Photoentrainment in Opn5-Null Mice.
AB  - The master circadian pacemaker in mammals resides in the hypothalamic
      suprachiasmatic nuclei (SCN) and is synchronized to ambient light/dark cycles
      (i.e., photoentrainment). Melanopsin (Opn4) and classical rod-cone photoreceptors
      are believed to provide all the photic input necessary for circadian
      photoentrainment. Although the UVA-sensitive photopigment Opn5 is known to be
      expressed in retinal ganglion cells, its physiological role remains unclear and a
      potential role for Opn5 in the photoentrainment of the master clock has not been
      addressed. Here we report impaired photoentrainment and phase shifting to UVA
      light in Opn5-null mice. However, triple-knockout mice lacking all known
      functional circadian photoreceptors (i.e., rods, cones, and melanopsin) failed to
      entrain to UVA-light/dark cycles, despite the presence of Opn5, demonstrating
      that Opn5 alone is not sufficient for photoentrainment of the SCN clock. Since
      Opn5 is involved in the regulation of the retinal circadian clock, disrupted
      retinal function may cause impaired circadian photoentrainment in Opn5-null mice.

PMID- 30240621
TI  - The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida
      Nociception.
AB  - Candida albicans infection can cause skin, vulvar, or oral pain. Despite the
      obvious algesic activity of C. albicans, the molecular mechanisms of fungal
      nociception remain largely unknown. Here we show that the C. albicans-specific
      signaling pathway led to severe mechanical allodynia. We discovered that C.
      albicans-derived beta-glucan stimulated nociceptors depending on Dectin-1, and
      two pathways in inflammatory pain. The major pathway operates via the Dectin-1
      mediated ATP-P2X3/P2X2/3 axis through intercellular relationships between
      keratinocytes and primary sensory neurons, which depends on the ATP transporter
      vesicular nucleotide transporter (VNUT). The other pathway operates via the
      Dectin-1-mediated PLC-TRPV1/TRPA1 axis in primary sensory neurons. Intriguingly,
      C. albicans-derived beta-glucan has the ability to enhance histamine-independent
      pruritus, and VNUT inhibitor clodronate can be used to treat unpleasant feelings
      induced by beta-glucan. Collectively, this is the first report to indicate that
      Dectin-1 and VNUT mediated innate sensory mechanisms that detect fungal
      infection.

PMID- 30240622
TI  - Temporal Cues Influence Space Estimations in Visually Impaired Individuals.
AB  - Many works have highlighted enhanced auditory processing in blind individuals,
      suggesting that they compensate for lack of vision with greater sensitivity of
      the other senses. Few years ago, we demonstrated severely impaired auditory
      precision in congenitally blind individuals performing an auditory spatial metric
      task: their thresholds for bisecting three consecutive spatially distributed
      sounds were seriously compromised, ranging from three times typical thresholds to
      total randomness. Here, we show that the deficit disappears if blind individuals
      are presented with coherent temporal and spatial cues. More interestingly, when
      the audio information is presented in conflict for space and time, sighted
      individuals are unaffected by the perturbation, whereas blind individuals are
      strongly attracted by the temporal cue. These results highlight that temporal
      cues influence space estimations in blind participants, suggesting for the first
      time that blind individuals use temporal information to infer spatial
      environmental coordinates.

PMID- 30240623
TI  - Infection Dynamics of a Bloom-Forming Alga and Its Virus Determine Airborne
      Coccolith Emission from Seawater.
AB  - Sea spray aerosols (SSA), have a profound effect on the climate; however, the
      contribution of oceanic microbial activity to SSA is not fully established. We
      assessed aerosolization of the calcite units (coccoliths) that compose the
      exoskeleton of the cosmopolitan bloom-forming coccolithophore, Emiliania huxleyi.
      Airborne coccolith emission occurs in steady-state conditions and increases by an
      order of magnitude during E. huxleyi infection by E. huxleyi virus (EhV).
      Airborne to seawater coccolith ratio is 1:108, providing estimation of airborne
      concentrations from seawater concentrations. The coccoliths' unique aerodynamic
      structure yields a characteristic settling velocity of ~0.01 cm s-1, ~25 times
      slower than average sea salt particles, resulting in coccolith fraction
      enrichment in the air. The calculated enrichment was established experimentally,
      indicating that coccoliths may be key contributors to coarse mode SSA surface
      area, comparable with sea salt aerosols. This study suggests a coupling between
      key oceanic microbial interactions and fundamental atmospheric processes like SSA
      formation.

PMID- 30240624
TI  - Highly Selective Transmission Success of Dengue Virus Type 1 Lineages in a
      Dynamic Virus Population: An Evolutionary and Fitness Perspective.
AB  - Arbovirus transmission is modulated by host, vector, virus, and environmental
      factors. Even though viral fitness plays a salient role in host and vector
      adaptation, the transmission success of individual strains in a heterogeneous
      population may be stochastic. Our large-scale molecular epidemiological analyses
      of a dengue virus type 1 population revealed that only a subset of strains
      (16.7%; n = 6) were able to sustain transmission, despite the population being
      widely dispersed, dynamic, and heterogeneous. The overall dominance was variable
      even among the "established" lineages, albeit sharing comparable evolutionary
      characteristics and replication profiles. These findings indicated that
      virological parameters alone were unlikely to have a profound effect on the
      survival of viral lineages, suggesting an important role for non-viral factors in
      the transmission success of lineages. Our observations, therefore, emphasize the
      strategic importance of a holistic understanding of vector, human host, and viral
      factors in the control of vector-borne diseases.

PMID- 30240625
TI  - Phosphorylation Alters the Properties of Pol eta: Implications for Translesion
      Synthesis.
AB  - There are significant ambiguities regarding how DNA polymerase eta is recruited
      to DNA lesion sites in stressed cells while avoiding normal replication forks in
      non-stressed cells. Even less is known about the mechanisms responsible for Pol
      eta-induced mutations in cancer genomes. We show that there are two safeguards to
      prevent Pol eta from adventitious participation in normal DNA replication. These
      include sequestration by a partner protein and low basal activity. Upon cellular
      UV irradiation, phosphorylation enables Pol eta to be released from sequestration
      by PDIP38 and activates its polymerase function through increased affinity toward
      monoubiquitinated proliferating cell nuclear antigen (Ub-PCNA). Moreover, the
      high-affinity binding of phosphorylated Pol eta to Ub-PCNA limits its subsequent
      displacement by Pol delta. Consequently, activated Pol eta replicates DNA beyond
      the lesion site and potentially introduces clusters of mutations due to its low
      fidelity. This mechanism could account for the prevalence of Pol eta signatures
      in cancer genome.

PMID- 30240626
TI  - Histone H2A.Z Suppression of Interferon-Stimulated Transcription and Antiviral
      Immunity Is Modulated by GCN5 and BRD2.
AB  - Type I interferon (IFN)-stimulated gene (ISG) expression requires interaction
      between a transcription factor complex, ISGF3, and target gene promoters to
      initiate transcription and protection against infection. To uncover chromatin
      regulatory features of this antiviral immune response, IFN-induced nucleosome and
      histone dynamics of human ISG loci were examined. ISGF3 recruitment after IFN
      stimulation was accompanied by nucleosome reorganization at promoters and gene
      bodies. IFN stimulation induced loss of core histones H2B, H3, and H4, as well as
      H2A.Z at ISG promoters. A strong correlation was found between H2A.Z occupancy
      and ISGF3 target sites, and IFN-stimulated H2A.Z removal requires STAT1, STAT2,
      and IRF9. Neither INO80 nor SWI/SNF participate in IFN-driven H2A.Z eviction, but
      GCN5 and BRD2 are required. Interference with H2A.Z expression enhanced ISGF3
      recruitment to ISG promoters, ISG mRNA expression, and IFN-stimulated antiviral
      immunity. This indicates that H2A.Z nucleosomes at ISG promoters restrict optimal
      ISGF3 engagement and modulate the biological response to IFN.

PMID- 30240628
TI  - Label-free 3D-CLEM Using Endogenous Tissue Landmarks.
AB  - Emerging 3D correlative light and electron microscopy approaches enable studying
      neuronal structure-function relations at unprecedented depth and precision.
      However, established protocols for the correlation of light and electron
      micrographs rely on the introduction of artificial fiducial markers, such as
      polymer beads or near-infrared brandings, which might obscure or even damage the
      structure under investigation. Here, we report a general applicable "flat
      embedding" preparation, enabling high-precision overlay of light and scanning
      electron micrographs, using exclusively endogenous landmarks in the brain: blood
      vessels, nuclei, and myelinated axons. Furthermore, we demonstrate feasibility of
      the workflow by combining in vivo 2-photon microscopy and focused ion beam
      scanning electron microscopy to dissect the role of astrocytic coverage in the
      persistence of dendritic spines.

PMID- 30240627
TI  - Three-Dimensional Analysis of Mitochondrial Crista Ultrastructure in a Patient
      with Leigh Syndrome by In Situ Cryoelectron Tomography.
AB  - Mitochondrial diseases produce profound neurological dysfunction via mutations
      affecting mitochondrial energy production, including the relatively common Leigh
      syndrome (LS). We recently described an LS case caused by a pathogenic mutation
      in USMG5, encoding a small supernumerary subunit of mitochondrial ATP synthase.
      This protein is integral for ATP synthase dimerization, and patient fibroblasts
      revealed an almost total loss of ATP synthase dimers. Here, we utilize in situ
      cryoelectron tomography (cryo-ET) in a clinical case-control study of
      mitochondrial disease to directly study mitochondria within cultured fibroblasts
      from a patient with LS and a healthy human control subject. Through tomographic
      analysis of patient and control mitochondria, we find that loss of ATP synthase
      dimerization due to the pathogenic mutation causes profound disturbances of
      mitochondrial crista ultrastructure. Overall, this work supports the crucial role
      of ATP synthase in regulating crista architecture in the context of human
      disease.

PMID- 30240629
TI  - Effect of prednisolone on linear growth in children with nephrotic syndrome.
AB  - OBJECTIVE: This study aims at determining the relationship between prednisolone
      cumulative dose and linear growth in pre-pubertal children with idiopathic
      nephrotic syndrome. METHOD: This cross-sectional study was conducted on all
      children with idiopathic nephrotic syndrome registered to the pediatric
      nephrology department at the main referral children's hospital in Southwestern
      Iran. Inclusion criteria included age (males <12 years; females <10 years), >6
      months of use, and the minimum prednisolone cumulative dose of 152mg/kg. The
      exclusion criteria were individuals who had entered puberty or had other diseases
      affecting linear growth. Based on the prednisolone cumulative dose of >=550mg/kg
      (four or more relapses), the children were divided into two groups. All data
      regarding age, height, and weight at disease onset and the last visit, bone age,
      and the parents' height were collected. Secondary variables including mid
      parental target height and predicted adult height were also calculated. Height
      data were compared between the different rates of relapse. RESULTS: A total of 97
      children (68% male) were enrolled. Their post-treatment mean height Z-score was
      less than that obtained before treatment (-0.584 vs. -0.158; p=0.001). Subjects
      with higher prednisolone cumulative doses were found to have more reduction in
      height Z-score (p=0.001). Post-treatment height prediction also showed less
      growth potential compared to pre-treatment target height (p=0.006). Thirty-three
      children (34.4%) had four or more relapses, among whom more mean-height Z-score
      decreases were found compared to those with less-frequent relapses (-0.84 vs. 
      0.28; p=0.04). CONCLUSION: This study showed the negative effect of cumulative
      dosages of prednisolone on linear growth, which was greater in children with four
      or more relapses.

PMID- 30240630
TI  - Patients with asthma have reduced functional capacity and sedentary behavior.
AB  - OBJECTIVE: The modified shuttle test (MST) is a field test that evaluates
      functional capacity. It is easy to perform, and avoids ceiling effect, however,
      MST was not used in pediatric asthmatic patients. Thus, the aim was to evaluate
      functional capacity by MST, additionally to perform a multidimensional assessment
      as physical activity in daily life, muscle strength, and cytokine levels in
      children and adolescents with asthma, and to correlate these variables. METHOD:
      This cross-sectional study included volunteers aged between 6 and 18 years who
      were divided into two groups: asthma group (n=43) that received regular treatment
      and control group (n=24). Functional capacity was evaluated by distance walked
      during the MST; physical activity in daily life was evaluated using an
      accelerometer by the number of steps. Quadriceps femoris strength was evaluated
      by load cell. RESULTS: Distance walked was lower for the asthma group (790m
      [222m]) when compared with the control group (950m [240m]; p=0.007); however, the
      number of steps was similar between the two groups (asthma group: 7743 [3075];
      control group: 7181 [3040]; p=0.41), and both groups were classified as sedentary
      behavior. There was no difference in muscle strength. Tumor necrosis factor-alpha
      differed, but interleukin levels were similar between groups. Quadriceps strength
      was correlated to distance walked (r=0.62; p<0.001) and tumor necrosis factor
      alpha to the number of steps taken (r=-0.54, p=0.005). CONCLUSION: Children and
      adolescents undergoing regular asthma treatment showed reduced functional
      capacity and sedentary behavior. The lower the quadriceps strength, the shorter
      the distance walked; the higher the tumor necrosis factor-alpha levels, the lower
      their daily physical activity levels.

PMID- 30240631
TI  - Treatment outcomes of children with acute lymphoblastic leukemia in a middle
      income developing country: high mortalities, early relapses, and poor survival.
AB  - OBJECTIVE: Acute lymphoblastic leukemia is the most common childhood cancer, yet
      surprisingly, very few studies have reported the treatment outcomes and the
      relapse rate of patients from low/middle-income countries. METHOD: This study was
      a 5-year retrospective cohort study. It was conducted at Oncology Center of
      Mansoura University in Egypt and aimed to estimate the treatment outcomes and the
      relapse rates of newly diagnosed acute lymphoblastic leukemia in children.
      RESULTS: Two hundred children suffering from acute lymphoblastic leukemia were
      studied; forty-six patients (23%) died during induction and most of those deaths
      were related to infection. Forty-one patients (27%) relapsed out of the 152
      patients who achieved complete remission. The most common site of relapse was the
      bone marrow, followed by the isolated central nervous system, 53.7% and 31.7%,
      respectively. Seventy-eight percent of relapses occurred very early/early rather
      than later. The majority of relapse patients' deaths were related to infection
      and disease progression. The 5-year overall survival rate for patients was 63.1%
      (82.1% for non-relapsed compared to 36.6% for relapsed patients). CONCLUSION:
      There was a high incidence of induction deaths related to infection and high
      percentages of very early/early relapses, with high mortalities and low 5-year
      overall survival rates. These findings suggest the urgent need for modification
      of chemotherapy regimens to be suitable for the local conditions, including
      implementation of supportive care and infection control policies. There is also a
      requirement for antimicrobial prophylaxis during induction period combined with
      the necessary increase in government healthcare spending to improve the survival
      of acute lymphoblastic leukemia in Egyptian children.

PMID- 30240632
TI  - In situ removal of consensus dengue virus envelope protein domain III fused to
      hydrophobin in Pichia pastoris cultures.
AB  - This work describes a novel strategy for the integrated expression and
      purification of recombinant proteins in Pichia pastoris cultures. Hydrophobins
      can be used as fusion tags, proteins fused to them alter their hydrophobicity and
      can be purified by aqueous two-phase systems (ATPS) based on non-ionic
      surfactants. Here, the consensus dengue virus envelope protein domain III fused
      to hydrophobin I of Trichoderma reesei was expressed in Pichia pastoris cultures
      and an in situ product removal by an ATPS using a non-ionic detergent, (Triton X
      114) was performed. The protein was produced and purified directly from the yeast
      culture supernatant both efficiently and with no loss. The purified protein was
      properly immobilized by adsorption in solid phase and recognized by anti-dengue
      antibodies, showing its potential for the development of an indirect immunoassay
      for dengue virus.

PMID- 30240633
TI  - Expression, purification and crystallization of the complex of RNA polymerase II
      carboxyl-terminal repeat domain kinase subunits CTK2-CTK3 from Saccharomyces
      cerevisiae.
AB  - Carboxyl-terminal repeat domain (CTD) of the largest subunit Rpb1 of RNA
      polymerace II is essential for transcription regulation. Heptapeptide repeat of
      CTD of Rpb1 is phosphorylated by carboxyl-terminal repeat domain kinase (CTDK-I),
      composed of CTK1, CTK2 and CTK3, in order to regulate transcription and
      transcription associated processes. The yeast specific protein CTK3 binds to
      cyclin CTK2 to form a heterodimer serving as a regulational factor to control
      CTK1 activity by binding to CTK1. Structural information of CTK2-CTK3 complex is
      yet to be elucidated. Here, we report the co-expression of CTK2-CTK3 complex from
      Saccharomyces cerevisiae with N-terminal His6-tag in CTK3 in Escherichia coli (E.
      coli), purification of the complex by four chromatographic steps and
      crystallization of the complex as well as the diffraction data collection and
      processing. This study provides some essential information and a guide for
      structural and functional study of CTK2-CTK3 complex and CTDK-I in the future.

PMID- 30240634
TI  - Neutrophils in tPA-induced hemorrhagic transformations: Main culprit, accomplice
      or innocent bystander?
AB  - The risk of intracerebral hemorrhage still greatly limits the use of tPA in
      stroke patients. Research is ongoing in order to identify the pathophysiological
      mechanisms at play, detect predictive biomarkers and discover new pharmacological
      targets to develop preventive or curative treatments. Going through experimental
      and clinical studies, this review focuses on the role of neutrophils as key
      predictive biomarkers for thrombolysis-induced hemorrhages and as pharmacological
      targets to limit their occurrence. To date, there are no established
      pharmacological modulators of neutrophils for ischemic stroke and its hemorrhagic
      complications. Several strategies are under evaluation, including lipid-lowering
      drugs, free radical scavengers, or minocycline, as well as non-pharmacological
      interventions such as physical exercise.

PMID- 30240635
TI  - Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung
      cancer.
AB  - Cytokines are pivotal mediators of the immune response, and their coordinated
      expression protects host tissue from excessive damage and oxidant stress.
      Nevertheless, the development of lung pathology, including asthma, chronic
      obstructive pulmonary disease, and ozone-induced lung injury, is associated with
      oxidant stress; as evidence, there is a significant increase in levels of the
      modified guanine base 7,8-dihydro-8-oxoguanine (8-oxoG) in the genome. 8-OxoG is
      primarily recognized by 8-oxoguanine glycosylase 1 (OGG1), which catalyzes the
      first step in the DNA base excision repair pathway. However, oxidant stress in
      the cell transiently halts enzymatic activity of substrate-bound OGG1. The
      stalled OGG1 facilitates DNA binding of transactivators, including NF-kappaB, to
      their cognate sites to enable expression of cytokines and chemokines, with
      ensuing recruitments of inflammatory cells. Hence, defective OGG1 will modulate
      the coordination between innate and adaptive immunity through excessive oxidant
      stress and cytokine dysregulation. Both oxidant stress and cytokine dysregulation
      constitute key elements of oncogenesis by KRAS, which is mechanistically coupled
      to OGG1. Thus, analysis of the mechanism by which OGG1 modulates gene expression
      helps discern between beneficial and detrimental effects of oxidant stress,
      exposes a missing functional link as a marker, and yields a novel target for lung
      cancer.

PMID- 30240637
TI  - Remote fear memory is sensitive to reconditioning.
AB  - Exposure of some individuals to recurring traumatic events from the same
      perpetrator or situation, such as during child abuse or domestic violence, is
      quite prevalent. Studies have shown that the number of traumatic events
      experienced is positively related to the severity of post-traumatic stress
      disorder and other mental disorders. Using a contextual fear conditioning (Cond1)
      and reconditioning (Cond2) paradigm, which were separated by either 1 or 35 days,
      we examined fear responses to immediate extinction and retrieval-extinction
      procedures after repeated fear conditioning stress. Based on the time interval
      between Cond1 and Cond2, the animals were divided into recent and remote fear
      memory groups. We observed that when Cond2 was performed in the original
      conditioning context in which Cond1 was performed, the reconditioned remote fear
      memory was resistant to the disruptive effect of immediate extinction and
      retrieval-extinction paradigms. Furthermore, the resistance to disruptive effects
      could be induced by very low shock intensities, which cannot even induce any fear
      response in naive animals. When Cond2 was performed in a novel context, animals
      with remote fear memory acquired a significantly higher fear response to the
      novel context. Our findings suggest that remote fear memory may be more sensitive
      to reconditioning and resistant to post-reconditioning disruption.

PMID- 30240636
TI  - Cucurbitacin E ameliorates acute graft-versus-host disease by modulating Th17
      cell subsets and inhibiting STAT3 activation.
AB  - Cucurbitacin E (CuE) is a biochemical compound found in plants that are members
      of the family CuE has been studied for its roles in anti-inflammation and the
      inhibition of angiogenesis as well as for its properties as an antioxidant. CuE
      is a new agent that was identified as a selective inhibitor of the signal
      transducer and activator of transcription 3 (STAT3)-related pathway. STAT3, a
      pivotal transcription factor for Th17 differentiation, is critical for T cell
      alloactivation in acute graft-versus-host disease (aGvHD). We investigated
      whether CuE attenuates the development of aGvHD through the suppression of Th17
      cells. The alloreactive proliferation of mouse and human T cells was reduced by
      CuE treatment. CuE also decreased pro-inflammatory cytokines, such as IL-17 and
      IFN-gamma, in alloreactive T cells. STAT3-responsive and IL-17A-promoter
      activities were also suppressed by CuE treatment, confirming that activated STAT3
      was decreased by CuE treatment. To construct an aGvHD-induced mouse line,
      splenocytes and bone marrow cells from C57BL/6 mice were transplanted into BALB/c
      mice with complete mis-matched major histocompatibility complex molecules. CuE
      was administered to aGvHD animals 3 days per week via intraperitoneal injection.
      CuE attenuated the severity of aGvHD disease-related scores compared to the
      vehicle group. CuE inhibited skin inflammation and fibrosis, as evidenced by the
      expression of alpha-Sma and Col-I in aGvHD mice compared to the vehicle group.
      Additionally, aGvHD mice treated with CuE showed improved histopathological
      features in the small and large intestines, whereas the vehicle group showed
      collapsed villi in the small intestine and cryptic structures in the large
      intestine. We also observed a marked reduction of pro-inflammatory cytokines in
      the intestinal tissue. Collectively, our data suggest that CuE could serve as a
      therapeutic agent for patients with aGvHD.

PMID- 30240638
TI  - To Eat or Not to Eat: Does Delaying Oral Feeding Decrease Anastomotic Leaks?

PMID- 30240639
TI  - Fragile X mental retardation protein regulates accumulation of the active zone
      protein Munc18-1 in presynapses via local translation in axons during
      synaptogenesis.
AB  - Fragile X mental retardation protein (FMRP), a causative gene (FMR1) product of
      Fragile X syndrome (FXS), is an RNA-binding protein to regulate local protein
      synthesis in dendrites for postsynaptic functions. However, involvement of FMRP
      in local protein synthesis in axons for presynaptic functions remains unclear.
      Here we investigated role of FMRP in local translation of the active zone protein
      Munc18-1 during presynapse formation. We found that leucine-rich repeat
      transmembrane neuronal 2 (LRRTM2)-conjugated beads, which promotes synchronized
      presynapse formation, induced simultaneous accumulation of FMRP and Munc18-1 in
      presynapses of axons of mouse cortical neurons in neuronal cell aggregate
      culture. The LRRTM2-induced accumulation of Munc18-1 in presynapses was observed
      in axons protein-synthesis-dependently, even physically separated from cell
      bodies. The accumulation of Munc18-1 was enhanced in Fmr1-knockout (KO) axons as
      compared to wild type (WT), suggesting FMRP-regulated suppression for local
      translation of Munc18-1 in axons during presynapse formation. Using naturally
      formed synapses of dissociated culture, structured illumination microscope
      revealed that accumulation of Munc18-1 puncta in Fmr1-KO neurons increased
      significantly at 19 days in vitro, as compared to WT. Our findings lead the
      possibility that excessive accumulation of Munc18-1 in presynapses at early stage
      of synaptic development in Fmr1-KO neurons may have a critical role in impaired
      presynaptic functions in FXS.

PMID- 30240640
TI  - Serine Phosphorylation by mTORC1 Promotes IRS-1 Degradation through SCFbeta-TRCP
      E3 Ubiquitin Ligase.
AB  - The insulin receptor substrate IRS-1 is a key substrate of insulin and insulin
      like growth factor (IGF) receptor tyrosine kinases that mediates their metabolic
      and growth-promoting actions. Proteasomal degradation of IRS-1 is induced
      following activation of the downstream kinase mTOR complex 1 (mTORC1) to
      constitute a negative feedback loop. However, the underlying mechanism remains
      poorly understood. Here we report that Ser 422 of IRS-1 is phosphorylated by
      mTORC1 and required for IRS-1 degradation induced by prolonged IGF stimulation.
      Phosphorylation of Ser 422 then recruits the SCFbeta-TRCP E3 ligase complex,
      which catalyzes IRS-1 ubiquitination. Phosphorylation-dependent IRS-1 degradation
      contributes to impaired growth and survival responses to IGF in cells lacking
      TSC2, a negative regulator of mTORC1. Inhibition of IRS-1 degradation promotes
      sustained Akt activation in IGF-stimulated cells. Our work clarifies the nature
      of the IRS-1-mTORC1 feedback loop and elucidates its role in temporal regulation
      of IGF signaling.

PMID- 30240641
TI  - Rapid Dehydroxytrifluoromethoxylation of Alcohols.
AB  - The CF3O functional group is a unique fluorinated group that has received a great
      deal of attention in medicinal chemistry and agrochemistry. However,
      trifluoromethoxylation of substrates remains a challenging task. Herein we
      describe the dehydroxytrifluoromethoxylation of alcohols promoted by a
      R3P/ICH2CH2I (R3P = Ph3P or Ph2PCH=CH2) system in DMF. P-I halogen bonding drives
      the reaction of R3P with ICH2CH2I in DMF to generate iodophosphonium salt (R3P+I
      I-) and a Vilsmeier-Haack-type intermediate, both of which could effectively
      activate alcohols, thus enabling a fast (15 min) trifluoromethoxylation reaction.
      A wide substrate scope and a high level of functional group tolerance were
      observed.

PMID- 30240642
TI  - Vasopressin Signal Inhibition in Aged Mice Decreases Mortality under Chronic Jet
      Lag.
AB  - Chronic jet lag, a model of shiftwork, increases mortality in aged mice. One
      potential reason for this association is that the chronic desynchronization
      between the internal clock phase and the environmental light/dark (LD) cycle
      might increase the mortality rate. However, this hypothesis has not been examined
      because of the lack of an appropriate animal model to prove this speculation.
      Here, we found that rapidly entrainable vasopressin receptor V1a-/-V1b-/- mice
      showed lower mortality under a chronic jet lag condition. Moreover, we found that
      pharmacological inactivation of V1a and V1b signaling decreased mortality even in
      aged wild-type mice, thus providing a potential pharmaceutical intervention for
      shiftwork-related health problems.

PMID- 30240643
TI  - Chromosomal Translocation Formation Is Sufficient to Produce Fusion Circular RNAs
      Specific to Patient Tumor Cells.
AB  - Circular RNAs constitute a unique class of RNAs whose precise functions remain to
      be elucidated. In particular, cancer-associated chromosomal translocations can
      give rise to fusion circular RNAs that play a role in leukemia progression.
      However, how and when fusion circular RNAs are formed and whether they are being
      selected in cancer cells remains unknown. Here, we used CRISPR/Cas9 to generate
      physiological translocation models of NPM1-ALK fusion gene. We showed that, in
      addition to generating fusion proteins and activating specific oncogenic
      pathways, chromosomal translocation induced by CRISPR/Cas9 led to the formation
      of de novo fusion circular RNAs. Specifically, we could recover different classes
      of circular RNAs composed of different circularization junctions, mainly back
      spliced species. In addition, we identified fusion circular RNAs identical to
      those found in related patient tumor cells providing evidence that fusion
      circular RNAs arise early after chromosomal formation and are not just a
      consequence of the oncogenesis process.

PMID- 30240644
TI  - Suspension Processing of Microporous Metal-Organic Frameworks: A Scalable Route
      to High-Quality Adsorbents.
AB  - Metal-Organic Frameworks (MOFs) have been intensively studied for applications
      such as gas storage, gas separation, catalysis, drug delivery, and more.
      Typically, the development of MOFs involves a post-synthetic solvent exchange
      process, which usually requires a significant investment of time, energy, labor,
      and resources. Herein, we propose a novel post-synthetic processing methodology
      for commercial and laboratory-scale MOFs called "Suspension Processing."
      Suspension processing is a non-destructive, agitation-based technique that
      provides efficient solvent exchange, pore cleaning, and surface defect removal in
      MOFs. Suspension processing has shown the capability to significantly improve the
      surface area and gas uptake properties of microporous MOFs, including PCN-250,
      UiO-66, and HKUST-1. Suspension processing displays improved time, energy, and
      labor efficiency, as well as considerably enhanced product quality. These
      findings confirm suspension processing as a straightforward methodology with
      applicability as a universal technique for the production of high-quality
      microporous materials.

PMID- 30240645
TI  - S-Adenosylmethionine Synthetase Is Required for Cell Growth, Maintenance of G0
      Phase, and Termination of Quiescence in Fission Yeast.
AB  - S-adenosylmethionine is an important compound, because it serves as the methyl
      donor in most methyl transfer reactions, including methylation of proteins,
      nucleic acids, and lipids. However, cellular defects in the genetic disruption of
      S-adenosylmethionine synthesis are not well understood. Here, we report the
      isolation and characterization of temperature-sensitive mutants of fission yeast
      S-adenosylmethionine synthetase (Sam1). Levels of S-adenosylmethionine and
      methylated histone H3 were greatly diminished in sam1 mutants. sam1 mutants
      stopped proliferating in vegetative culture and arrested specifically in G2 phase
      without cell elongation. Furthermore, sam1 mutants lost viability during nitrogen
      starvation-induced G0 phase quiescence. After release from the G0 state, sam1
      mutants could neither increase in cell size nor re-initiate DNA replication in
      the rich medium. Sam1 is thus required for cell growth and proliferation, and
      maintenance of and exit from quiescence. sam1 mutants lead to broad cellular and
      drug response defects, as expected, since S. pombe contains more than 90 S
      adenosylmethionine-dependent methyltransferases.

PMID- 30240646
TI  - Data and Power Efficient Intelligence with Neuromorphic Learning Machines.
AB  - The success of deep networks and recent industry involvement in brain-inspired
      computing is igniting a widespread interest in neuromorphic hardware that
      emulates the biological processes of the brain on an electronic substrate. This
      review explores interdisciplinary approaches anchored in machine learning theory
      that enable the applicability of neuromorphic technologies to real-world, human
      centric tasks. We find that (1) recent work in binary deep networks and
      approximate gradient descent learning are strikingly compatible with a
      neuromorphic substrate; (2) where real-time adaptability and autonomy are
      necessary, neuromorphic technologies can achieve significant advantages over main
      stream ones; and (3) challenges in memory technologies, compounded by a tradition
      of bottom-up approaches in the field, block the road to major breakthroughs. We
      suggest that a neuromorphic learning framework, tuned specifically for the
      spatial and temporal constraints of the neuromorphic substrate, will help guiding
      hardware algorithm co-design and deploying neuromorphic hardware for proactive
      learning of real-world data.

PMID- 30240647
TI  - Histopathological Image QTL Discovery of Immune Infiltration Variants.
AB  - Genotype-to-phenotype association studies typically use macroscopic physiological
      measurements or molecular readouts as quantitative traits. There are
      comparatively few suitable quantitative traits available between cell and tissue
      length scales, a limitation that hinders our ability to identify variants
      affecting phenotype at many clinically informative levels. Here we show that
      quantitative image features, automatically extracted from histopathological
      imaging data, can be used for image quantitative trait loci (iQTLs) mapping and
      variant discovery. Using thyroid pathology images, clinical metadata, and
      genomics data from the Genotype-Tissue Expression (GTEx) project, we establish
      and validate a quantitative imaging biomarker for immune cell infiltration. A
      total of 100,215 variants were selected for iQTL profiling and tested for
      genotype-phenotype associations with our quantitative imaging biomarker.
      Significant associations were found in HDAC9 and TXNDC5. We validated the TXNDC5
      association using GTEx cis-expression QTL data and an independent hypothyroidism
      dataset from the Electronic Medical Records and Genomics network.

PMID- 30240648
TI  - Persistent Increases of PKMzeta in Sensorimotor Cortex Maintain Procedural Long
      Term Memory Storage.
AB  - Procedural motor learning and memory are accompanied by changes in synaptic
      plasticity, neural dynamics, and synaptogenesis. Missing is information on the
      spatiotemporal dynamics of the molecular machinery maintaining these changes.
      Here we examine whether persistent increases in PKMzeta, an atypical protein
      kinase C (PKC) isoform, store long-term memory for a reaching task in rat
      sensorimotor cortex that could reveal the sites of procedural memory storage.
      Specifically, perturbing PKMzeta synthesis (via antisense oligodeoxynucleotides)
      and blocking atypical PKC activity (via zeta inhibitory peptide [ZIP]) in S1/M1
      disrupts and erases long-term motor memory maintenance, indicating atypical PKCs
      and specifically PKMzeta store consolidated long-term procedural memories.
      Immunostaining reveals that PKMzeta increases in S1/M1 layers II/III and V as
      performance improved to an asymptote. After storage for 1 month without
      reinforcement, the increase in M1 layer V persists without decrement. Thus, the
      persistent increases in PKMzeta that store long-term procedural memory are
      localized to the descending output layer of the primary motor cortex.

PMID- 30240650
TI  - Cesarean scar defect: a prospective study on risk factors.
AB  - BACKGROUND: Cesarean scar defect (isthmocele) is a known complication after
      cesarean delivery. It has become more common due to a rising cesarean delivery
      rate. Isthmocele has been associated with various gynecological and obstetric
      problems such as uterine rupture, cesarean scar pregnancy, and bleeding
      disorders. OBJECTIVE: We sought to prospectively investigate factors associated
      with the risk for isthmocele assessed by sonohysterography. STUDY DESIGN: A
      prospective observational cohort study was conducted in 401 nonpregnant women who
      were recruited within 3 days of cesarean delivery. Women were evaluated with
      sonohysterography 6 months after cesarean delivery to detect a possible
      isthmocele. The ultrasonographer was blinded to any clinical information. The
      main outcome measure was the presence of isthmocele. Type of surgery (elective vs
      emergency), maternal background variables, and factors related to pregnancy,
      labor, and postoperative recovery were analyzed in relation to isthmocele. A
      logistic regression model was used to assess independent risk factors from
      univariate analysis. RESULTS: In all, 371 women were examined with
      sonohysterography resulting in a follow-up rate of 92.5%. The prevalence of
      isthmocele was 45.6%. Independent risk factors for isthmocele development were a
      history of gestational diabetes (odds ratio, 1.73; 95% confidence interval, 1.02
      2.92; P = .042), previous cesarean delivery (odds ratio, 3.14; 95% confidence
      interval, 1.90-5.17; P < .001), and advanced maternal body mass index (odds
      ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .012). Every additional unit
      of body mass index increased the risk of isthmocele by 6%. In the subgroup of
      emergency cesarean delivery, longer duration of active labor increased the risk
      for isthmocele (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .032).
      There was no statistically significant difference in prevalence between the
      groups of elective and emergency cesarean delivery (P = .898). CONCLUSION: Based
      on sonohysterographic examination, maternal body mass index, gestational
      diabetes, and previous cesarean deliveries are associated with an increased risk
      for incomplete healing of the uterine incision.

PMID- 30240649
TI  - Initial B Cell Activation Induces Metabolic Reprogramming and Mitochondrial
      Remodeling.
AB  - B lymphocytes provide adaptive immunity by generating antigen-specific antibodies
      and supporting the activation of T cells. Little is known about how global
      metabolism supports naive B cell activation to enable an effective immune
      response. By coupling RNA sequencing (RNA-seq) data with glucose isotopomer
      tracing, we show that stimulated B cells increase programs for oxidative
      phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and nucleotide
      biosynthesis, but not glycolysis. Isotopomer tracing uncovered increases in TCA
      cycle intermediates with almost no contribution from glucose. Instead, glucose
      mainly supported the biosynthesis of ribonucleotides. Glucose restriction did not
      affect B cell functions, yet the inhibition of OXPHOS or glutamine restriction
      markedly impaired B cell growth and differentiation. Increased OXPHOS prompted
      studies of mitochondrial dynamics, which revealed extensive mitochondria
      remodeling during activation. Our results show how B cell metabolism adapts with
      stimulation and reveals unexpected details for carbon utilization and
      mitochondrial dynamics at the start of a humoral immune response.

PMID- 30240651
TI  - Intrapartum magnesium sulfate is associated with neuroprotection in growth
      restricted fetuses.
AB  - BACKGROUND: Intrapartum magnesium sulfate administration is recommended for fetal
      neuroprotection in women with imminent very preterm birth. However, previous
      studies have not included or separately analyzed the outcomes of pregnancies with
      fetal growth restriction that were treated with intrapartum magnesium sulfate.
      OBJECTIVE: We sought to evaluate the neonatal and neurodevelopmental outcomes of
      growth-restricted fetuses born <29 weeks' gestation and exposed to maternal
      intrapartum magnesium sulfate. STUDY DESIGN: We conducted a retrospective cohort
      study of infants born <29 weeks' gestation from 2010 through 2011, admitted to
      participating Canadian Neonatal Network units, and followed by the Canadian
      Neonatal Follow-up Network centers. Growth restriction was defined either as
      estimated fetal or actual neonatal birthweight <10th percentile according to
      fetal or neonatal growth standards for gestational age and sex, respectively.
      Infants exposed to intrapartum magnesium sulfate were compared with unexposed
      infants. The primary outcome was composite of death or significant
      neurodevelopmental impairment at 18-36 months' corrected age. Secondary outcomes
      were death or any neurodevelopmental impairment at 18-36 months' corrected age.
      Neonatal morbidities were also compared. RESULTS: Of the 336 growth-restricted
      fetuses, 112 (33%) received magnesium sulfate and of the 177 growth-restricted
      infants, 61 (34%) received magnesium sulfate. Administration of magnesium sulfate
      was at the discretion of the treating physician. Intrapartum magnesium sulfate
      was associated with reduced odds of composite of death or significant
      neurodevelopmental impairment for infants classified according to both fetal
      standards (adjusted odds ratio, 0.42; 95% confidence interval, 0.22-0.80) and
      neonatal standards (adjusted odds ratio, 0.44; 95% confidence interval, 0.20
      0.98). CONCLUSION: Intrapartum administration of magnesium sulfate to women with
      growth-restricted fetuses born <29 weeks' gestation was associated with reduced
      odds of composite of death or significant neurodevelopmental impairment.

PMID- 30240652
TI  - Reply.

PMID- 30240653
TI  - Prediction of spontaneous preterm delivery in women presenting with premature
      labor: a comparison of placenta alpha microglobulin-1, phosphorylated insulin
      like growth factor binding protein-1, and cervical length.
AB  - BACKGROUND: Placental alpha microglobulin-1 and phosphorylated insulin-like
      growth factor-binding protein-1 have been studied in patients at risk for preterm
      birth with signs and symptoms of preterm labor. However, a direct comparison
      between these 2 biomarkers, alone or in combination with cervical length
      measurement with an adequate sample size, has been lacking to date. OBJECTIVE:
      The purpose of this study was to compare the placental alpha microglobulin-1 test
      and the phosphorylated insulin-like growth factor-binding protein-1 test alone
      and in combination with cervical length measurement for the prediction of
      imminent spontaneous preterm birth of testing in pregnant women with symptoms of
      preterm labor in a tertiary care setting. STUDY DESIGN: Four hundred three
      patients with intact amniotic membranes and cervical dilation <=3 cm, without
      recent intercourse or cerclage, between gestational weeks of 20+0 and 36+6 were
      recruited prospectively from 3 international centers. Placental alpha
      microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1
      tests were conducted before cervical length measurement via transvaginal
      ultrasound scanning. Caregivers were blinded to the biomarker test results.
      Medically indicated deliveries within 14 days of testing were excluded. Standard
      performance statistics with 95% confidence intervals were calculated and compared
      based on pairwise estimates from a generalized model. RESULTS: Of 403 subjects
      who were enrolled in the study cohort, 94% (383/403 women) met the inclusion
      criteria. Median gestational age and cervical length at presentation were 30+5
      weeks and 27 mm, respectively; 6.8% women (26/383 women) had spontaneous birth
      <=7 days from testing. The placental alpha microglobulin-1 test was positive in
      7.8% of the women (30/383 women); the phosphorylated insulin-like growth factor
      binding protein-1 test was positive in 29.5% women (113/383 women). Positive
      predictive value for placental alpha microglobulin-1, phosphorylated insulin-like
      growth factor-binding protein-1, and cervical length <25 mm for the prediction of
      spontaneous preterm birth in the overall cohort was 60.0% (18/30 women), 18.6%
      (21/113 women), 11.8% (18/152 women), respectively. The negative predictive value
      was 97.7% (345/353 women), 98.2% (265/270 women), 96.5% (223/231 women),
      respectively. The prevalence of spontaneous preterm birth in this group was 6.8%
      (26/383 women). The positive likelihood ratios were 20.6, 3.1, and 1.8,
      respectively. The negative likelihood ratio were 0.3, 0.3, and 0.5, respectively.
      Positive predictive values for placental alpha microglobulin-1 and phosphorylated
      insulin-like growth factor-binding protein-1 tests in patients with cervical
      length shortening of 15-30 mm for the prediction of spontaneous preterm birth
      were 60.9% (14/23 women) and 28.1% (16/57 women), respectively. The negative
      predictive values were 97.1% (168/173 women) and 97.8% (136/139 women),
      respectively. The prevalence of spontaneous preterm birth in the 15-30 mm cohort
      was 9.7% (19/196 women). The positive likelihood ratios were 14.5 and 3.6,
      respectively. The negative likelihood ratios were 0.3 and 0.2, respectively.
      CONCLUSION: Placental alpha microglobulin-1 is significantly more specific than
      phosphorylated insulin-like growth factor-binding protein-1 for the prediction of
      spontaneous preterm birth <=7 days (P<.0001), whereas both tests have comparable
      sensitivity. In patients with cervical length 15-30 mm, although placental alpha
      microglobulin-1 has a significantly higher positive predictive value and
      specificity compared with phosphorylated insulin-like growth factor-binding
      protein-1 for the prediction of spontaneous preterm birth at <=7 days (P<.01),
      both tests have a comparable sensitivity and negative predictive value. In
      conclusion, placental alpha microglobulin-1 is a better predictor of imminent
      spontaneous preterm birth when compared with phosphorylated insulin-like growth
      factor-binding protein-1 alone or in combination with cervical length
      measurement. In patients with shortening of cervical length of 15-30 mm, the
      placental alpha microglobulin-1 test is a significantly better predictor of
      imminent spontaneous preterm birth within 7 days of testing than is
      phosphorylated insulin-like growth factor-binding protein-1.

PMID- 30240654
TI  - Medical education research in obstetrics and gynecology.

PMID- 30240655
TI  - A preoperative risk score to predict red blood cell transfusion in patients
      undergoing hysterectomy for ovarian cancer.
AB  - BACKGROUND: Patients with ovarian cancer experience a high rate of anemia
      throughout their treatment course, with rates that range from 19-95%. Blood
      transfusions offer symptom relief but may be costly, are limited in supply, and
      have been associated with worse 30-day surgical morbidity and mortality rates.
      OBJECTIVE: The purpose of this study was to identify risk factors for blood
      transfusion with packed red blood cell and to develop a transfusion risk score to
      identify patients who undergo surgery for ovarian cancer and who are at lowest
      risk for a blood transfusion. Our aim was to help clinicians identify those
      patients who may not require a crossmatch to encourage resource use and cost
      savings. STUDY DESIGN: This is a retrospective database cohort study of 3470
      patients who underwent hysterectomy for ovarian cancer with the use the National
      Surgical Quality Improvement Program database from 2014-2016. The association
      between risk factors with respect to 30-day postoperative blood transfusion was
      modeled with the use of logistic regression. A risk score to predict blood
      transfusion was created. RESULTS: Eight hundred ninety-one (25.7%) patients
      received a blood transfusion. In multivariate analysis, blood transfusion was
      associated independently with age (odds ratio, 1.90, P<.01), African American
      race (odds ratio, 2.30; P<.01), ascites (odds ratio, 1.89; P=.02), preoperative
      hematocrit level <30% (odds ratio, 10.70; P<.01), preoperative platelet count
      >400*109/L (odds ratio, 1.75; P<.01), occurrence of disseminated cancer (odds
      ratio, 1.71; P<.01), open surgical approach (odds ratio, 7.88; P<.01), operative
      time >3 hours (odds ratio, 2.19; P<.01), and additional surgical procedures that
      included large bowel resection (odds ratio, 4.23; P<.01), bladder/ureter
      resection (odds ratio, 1.69; P=.02), and pelvic exenteration (P=.02). A
      preoperative risk score that used age, race, ascites, preoperative hematocrit
      level, platelets, presence of disseminated cancer, planned hysterectomy approach,
      and procedures accurately predicted blood transfusion with good discriminatory
      ability (C-statistic=0.80 [P<.001]; C-statistic=0.69 [P<.001] for derivation and
      validation datasets, respectively) and calibration (Hosmer-Lemeshow goodness-of
      fit, P=.081; P=.56 for derivation and validation datasets, respectively).
      CONCLUSION: Patients who undergo hysterectomy for ovarian cancer experience a
      high incidence of blood transfusions in the perioperative period. Preoperative
      risk factors and planned surgical procedures can be used in our transfusion risk
      score to help predict anticipated blood requirements.

PMID- 30240656
TI  - Female pelvic medicine and reconstructive surgery fellows' exposure to
      transgender health care.

PMID- 30240657
TI  - Guidelines for Antenatal and Preoperative care in Cesarean Delivery: Enhanced
      Recovery After Surgery Society Recommendations (Part 1).
AB  - This Enhanced Recovery After Surgery (ERAS) Guideline for perioperative care in
      cesarean delivery will provide best practice, evidenced-based, recommendations
      for preoperative, intraoperative, and postoperative phases with, primarily, a
      maternal focus. The focused pathway process for scheduled and unscheduled
      cesarean delivery for this ERAS Cesarean Delivery Guideline will consider from
      the time from decision to operate (starting with the 30-60 minutes before skin
      incision) to hospital discharge. The literature search (1966-2017) used Embase
      and PubMed to search medical subject headings that included "Cesarean Section,"
      "Cesarean Section," "Cesarean Section Delivery" and all pre- and intraoperative
      ERAS items. Study selection allowed titles and abstracts to be screened by
      individual reviewers to identify potentially relevant articles. Metaanalyses,
      systematic reviews, randomized controlled studies, nonrandomized controlled
      studies, reviews, and case series were considered for each individual topic.
      Quality assessment and data analyses that evaluated the quality of evidence and
      recommendations were evaluated according to the Grading of Recommendations,
      Assessment, Development and Evaluation system, as used and described in previous
      ERAS Guidelines. The ERAS Cesarean Delivery Guideline/Pathway has created a
      maternal focused pathway (for scheduled and unscheduled surgery starting from 30
      60 minutes before skin incision to maternal discharge) with ERAS cesarean
      delivery consensus recommendations preoperative elements (anesthetic medications,
      fasting, carbohydrate supplementation, prophylactic antibiotics/skin preparation,
      ), intraoperative elements (anesthetic management, maternal hypothermia
      prevention, surgical technique, hysterotomy creation and closure, management of
      peritoneum, subcutaneous space, and skin closure), perioperative fluid
      management, and postoperative elements (chewing gum, management of nausea and
      vomiting, analgesia, timing of food intake, glucose management, antithrombotic
      prophylaxis, timing of ambulation, urinary management, and timing of maternal and
      neonate discharge). Limited topics for optimized care and for antenatal education
      and counselling and the immediate neonatal needs at delivery are discussed.
      Strong recommendations for element use were given for preoperative (antenatal
      education and counselling, use of antacids and histamine, H2 receptor
      antagonists, 2-hour fasting and small meal within 6 hours surgery, antimicrobial
      prophylaxis and skin preparation/chlorhexidine-alcohol), intraoperative (regional
      anesthesia, prevention of maternal hypothermia [forced warm air, warmed
      intravenous fluids, room temperature]), perioperative (fluid management for
      euvolemia and neonatal immediate care needs that include delayed cord clamping),
      and postoperative (fluid management to prevent nausea and vomiting, antiemetic
      use, analgesia with nonsteroidal antiinflammatory drugs/paracetamol, regular diet
      within 2 hours, tight capillary glucose control, pneumatic compression stocking
      for venous thromboembolism prophylaxis, immediate removal of urinary catheter).
      Recommendations against the element use were made for preoperative (maternal
      sedation, bowel preparation), intraoperative (neonatal oral suctioning or
      increased inspired oxygen), and postoperative (heparin should not be used
      routinely venous thromboembolism prophylaxis). Because these ERAS cesarean
      delivery pathway recommendations (elements/processes) are studied, implemented,
      audited, evaluated, and optimized by the maternity care teams, this will create
      an opportunity for the focused and optimized areas of care research with further
      enhanced care and recommendation.

PMID- 30240658
TI  - Preventing incremental drift away from professionalism in graduate medical
      education.
AB  - Professionalism is a core competency of graduate medical education programs,
      stipulated by the Accreditation Council for Graduate Medical Education. We
      identify an underappreciated challenge to professionalism in residency training,
      the risk of incremental drift from professionalism, and a preventive ethics
      response, which can occur in residency programs in countries with oversight
      similar to that of the Accreditation Council for Graduate Medical Education. Two
      major, welcome changes in graduate medical education-required duty hours and
      increased attending supervision-create incentives for drift from professionalism.
      This article analyzes these incentives based on the ethical concept of medicine
      as a profession, introduced into the history of medical ethics in late 18th
      century Britain. This concept calls for physicians to make 3 commitments: to
      scientific and clinical competence; to the protection and promotion of the
      patient's health-related interests; and to keeping individual and group self
      interest systematically secondary. Some responses of programs and residents to
      these incentives can undermine professionalism, creating a subtle and therefore
      hard-to-detect drift away from professionalism that in its worst form results in
      infantilization of residents. Program directors and educators should prevent this
      drift from professionalism by implementing practices that promote professionally
      responsible responses to the incentives created by required duty hours and
      increased attending supervision.

PMID- 30240659
TI  - Guild interests: an insidious threat to professionalism in obstetrics and
      gynecology.
AB  - Powerful incentives now exist that could subordinate professionalism to guild
      self-interest. How obstetrician-gynecologists respond to these insidious
      incentives will determine whether guild self-interests will define our specialty.
      We provide ethically justified, practical guidance to obstetrician-gynecologists
      to prevent this ethically unacceptable outcome. We describe and illustrate 2
      major incentives to subordinating professionalism to guild self-interest: demands
      for productivity; and compliance and regulatory pressures. We then set out the
      professional responsibility model of ethics in obstetrics and gynecology to guide
      obstetrician-gynecologists in responding to these incentives so that they
      preserve professionalism. Obstetrician-gynecologists should identify guild
      interests affecting their group practices, set ethically justified limits on self
      sacrifice, and prevent incremental drift toward dominance of guild self-interests
      over professionalism. Guild self-interests could succeed in undermining
      professionalism, but only if obstetrician-gynecologists allow this to happen.
      When guild self-interest becomes the deciding factor in patient care,
      professionalism withers and insidious incentives flourish.

PMID- 30240660
TI  - Dexmedetomidine ameliorates lidocaine-induced spinal neurotoxicity via inhibiting
      glutamate release and the PKC pathway.
AB  - Dexmedetomidine, a selective alpha2 adrenergic agonist, has been shown to have
      neuroprotective and anti-apoptotic effects. To further investigate the underlying
      mechanisms, we used a rat model of spinal neurotoxicity induced by intrathecal
      administration of lidocaine. Four days after intrathecal catheter implantation,
      rats received an intraperitoneal injection of various doses of dexmedetomidine
      before an intrathecal injection of 20 MUL 10% lidocaine. Dexmedetomidine
      pretreated rats were also exposed to a selective alpha2-adrenergic antagonist
      (yohimbine) or a specific protein kinase C (PKC) inhibitor (Go 6983) that
      selectively inhibits several PKC isoforms. Lidocaine injection significantly
      damaged the spinal cord: hind limb locomotor function was reduced and tail-flick
      latency was prolonged; significant spinal cord damage and neuronal apoptosis were
      identified using histological and TUNEL staining assays; increased glutamate
      release was detected using high performance liquid chromatography (HPLC)
      analysis; and increased expression of PKC and PKCbetaI was detected using Western
      blotting analysis. Pretreatment with dexmedetomidine ameliorated all of the
      lidocaine-induced effects; however, this protection was abolished when yohimbine
      or Go 6983 was injected together with dexmedetomidine. Our results indicate that
      dexmedetomidine protects the spinal cord from lidocaine-induced spinal
      neurotoxicity through regulating PKC expression and glutamate release.

PMID- 30240662
TI  - Intending to Treat Patients With Irritable Bowel Syndrome With Cognitive
      Behavioral Therapy.

PMID- 30240663
TI  - Abdominal pain presenting as a tight squeeze on a Tchaikovsky score.

PMID- 30240664
TI  - Abdominal pain and prolonged fever of unknown cause in a 14-year-old boy.

PMID- 30240661
TI  - Circulating Nucleic Acids Are Associated With Outcomes of Patients With
      Pancreatic Cancer.
AB  - BACKGROUND & AIMS: We aimed to investigate the clinical utility of circulating
      tumor cell DNA (ctDNA) and exosome DNA (exoDNA) in pancreatic cancer. METHODS: We
      collected liquid biopsy samples from 194 patients undergoing treatment for
      localized or metastatic pancreatic adenocarcinoma from April 7, 2015, through
      October 13, 2017 (425 blood samples collected before [baseline] and during
      therapy). Additional liquid biopsy samples were collected from 37 disease control
      individuals. Droplet digital polymerase chain reaction was used to determine KRAS
      mutant allele fraction (MAF) from ctDNA and exoDNA purified from plasma. For the
      longitudinal analysis, we analyzed exoDNA and ctDNA in 123 serial blood samples
      from 34 patients. We performed analysis including Cox regression, Fisher exact
      test, and Bayesian inference to associate KRAS MAFs in exoDNA and ctDNA with
      prognostic and predictive outcomes. RESULTS: In the 34 patients with potentially
      resectable tumors, an increase in exoDNA level after neoadjuvant therapy was
      significantly associated with disease progression (P = .003), whereas ctDNA did
      not show correlations with outcomes. Concordance rates of KRAS mutations present
      in surgically resected tissue and detected in liquid biopsy samples were greater
      than 95%. On univariate analysis, patients with metastases and detectable ctDNA
      at baseline status had significantly shorter times of progression-free survival
      (PFS) (hazard ratio [HR] for death, 1.8; 95% confidence interval [CI], 1.1-3.0; P
      = .019), and overall survival (OS) (HR, 2.8; 95% CI, 1.4-5.7; P = .0045) compared
      with patients without detectable ctDNA. On multivariate analysis, MAFs >=5% in
      exoDNA were a significant predictor of PFS (HR, 2.28; 95% CI, 1.18-4.40; P =
      .014) and OS (HR, 3.46; 95% CI, 1.40-8.50; P = .007). A multianalyte approach
      showed detection of both ctDNA and exoDNA MAFs >=5% at baseline status to be a
      significant predictor of OS (HR, 7.73, 95% CI, 2.61-22.91, P = .00002) on
      multivariate analysis. In the longitudinal analysis, an MAF peak above 1% in
      exoDNA was significantly associated with radiologic progression (P = .0003).
      CONCLUSIONS: In a prospective cohort of pancreatic cancer patients, we show how
      longitudinal monitoring using liquid biopsy samples through exoDNA and ctDNA
      provides both predictive and prognostic information relevant to therapeutic
      stratification.

PMID- 30240665
TI  - A Hypervascular Pancreatic Tumor.

PMID- 30240666
TI  - A Shiny Liver!

PMID- 30240667
TI  - Unusual etiology for sub-acute terminal ileitis in a 5 year old.

PMID- 30240668
TI  - Abdominal Pain and Constipation.

PMID- 30240669
TI  - A first ileus event in an elderly man with malrotation.

PMID- 30240670
TI  - Submucosal Lesion in the Cecum- to Biopsy or Not to Biopsy.

PMID- 30240671
TI  - A Rare Cause of Gastrointestinal Bleeding in a Patient With a History of
      Alcoholic Cirrhosis.

PMID- 30240672
TI  - A Rare Cause of Liver Herniation.

PMID- 30240673
TI  - A case of recurring diarrhea in a young woman.

PMID- 30240674
TI  - Error of Omission.

PMID- 30240675
TI  - An Unusual Cause of Recurrent Epigastric Pain.

PMID- 30240677
TI  - Marijuana's Effects on Brain Structure and Function: What Do We Know and What
      Should We Do? A Brief Review and Commentary.
AB  - The recent US Food and Drug Administration approval of the marijuana constituent
      cannabidiol as safe and effective for treatment of 2 rare forms of epilepsy has
      raised hopes that others of the 500 chemicals in marijuana will be found to be
      therapeutic. However, the long-term consequences of street marijuana use are
      unclear, and recent studies raise red flags about its effects. Changes in brain
      maturation and intellectual function, including decreases in intelligence
      quotient, have been noted in chronic users and appear permanent in early users in
      most but not all studies. These studies suggest that at a minimum, regular
      marijuana use should be discouraged in individuals under the age of 21.

PMID- 30240678
TI  - Sarcoidosis presenting as isolated anasarca and hypercalcemia.

PMID- 30240679
TI  - Fixed-dose combination amlodipine/celecoxib (ConsensiTM) for hypertension and
      osteoarthritis.
AB  - The U.S. Food and Drug Administration recently granted an approved indication for
      the first fixed-dose combination antihypertensive (amlodipine) and non-steroidal
      anti-inflammatory drug (celecoxib) for treatment of comorbid hypertension and
      osteoarthritis. This review summarizes available data on this combination
      product, to be marketed as ConsensiTM (Kitov Pharmaceuticals, Ltd, Tel Aviv,
      Israel), and discusses its potential place in therapy.

PMID- 30240676
TI  - beta-adrenergic regulation of late Na+ current during cardiac action potential is
      mediated by both PKA and CaMKII.
AB  - Late Na+ current (INaL) significantly contributes to shaping cardiac action
      potentials (APs) and increased INaL is associated with cardiac arrhythmias. beta
      adrenergic receptor (betaAR) stimulation and its downstream signaling via protein
      kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) pathways
      are known to regulate INaL. However, it remains unclear how each of these
      pathways regulates INaL during the AP under physiological conditions. Here we
      performed AP-clamp experiments in rabbit ventricular myocytes to delineate the
      impact of each signaling pathway on INaL at different AP phases to understand the
      arrhythmogenic potential. During the physiological AP (2 Hz, 37  degrees C) we
      found that INaL had a basal level current independent of PKA, but partially
      dependent on CaMKII. betaAR activation (10 nM isoproterenol, ISO) further
      enhanced INaL via both PKA and CaMKII pathways. However, PKA predominantly
      increased INaL early during the AP plateau, whereas CaMKII mainly increased INaL
      later in the plateau and during rapid repolarization. We also tested the role of
      key signaling pathways through exchange protein activated by cAMP (Epac), nitric
      oxide synthase (NOS) and reactive oxygen species (ROS). Direct Epac stimulation
      enhanced INaL similar to the betaAR-induced CaMKII effect, while NOS inhibition
      prevented the betaAR-induced CaMKII-dependent INaL enhancement. ROS generated by
      NADPH oxidase 2 (NOX2) also contributed to the ISO-induced INaL activation early
      in the AP. Taken together, our data reveal differential modulations of INaL by
      PKA and CaMKII signaling pathways at different AP phases. This nuanced and
      comprehensive view on the changes in INaL during AP deepens our understanding of
      the important role of INaL in reshaping the cardiac AP and arrhythmogenic
      potential under elevated sympathetic stimulation, which is relevant for designing
      therapeutic treatment of arrhythmias under pathological conditions.

PMID- 30240680
TI  - Assessment and Treatment of Physician Speechlessness.

PMID- 30240681
TI  - Granulomatosis with Polyangiitis Presenting as Hypophysitis.

PMID- 30240682
TI  - Diagnostic and Management Dilemma: Massive Hemoptysis from Severe Mitral
      Stenosis.

PMID- 30240683
TI  - Asking How Our Patients Understand Addiction.

PMID- 30240684
TI  - The Art of Nitpicking.

PMID- 30240685
TI  - Bilateral Breast Ulcers: Granulomatosis with Polyangiitis.

PMID- 30240687
TI  - Program Coordinator Professional Development: Definition, Perception of
      Importance, Motivating Factors and Barriers.
AB  - A program coordinator's work and continued development have direct impact on.

PMID- 30240686
TI  - Spironolactone and Outcomes in Older Patients with Heart Failure and Reduced
      Ejection Fraction.
AB  - BACKGROUND: The efficacy of mineralocorticoid receptor antagonists or aldosterone
      antagonists in heart failure with reduced ejection fraction (HFrEF) is well
      known. Less is known about their effectiveness in real-world older patients with
      HFrEF. METHODS: Of the 8206 patients with heart failure and ejection fraction
      <=35% without prior spironolactone use in the Medicare-linked OPTIMIZE-HF
      registry, 6986 were eligible for spironolactone therapy based on serum creatinine
      criteria (men <=2.5 mg/dL, women <=2.0 mg/dL) and 865 received a discharge
      prescription for spironolactone. Using propensity scores for spironolactone use,
      we assembled a matched cohort of 1724 (862 pairs) patients receiving and not
      receiving spironolactone, balanced on 58 baseline characteristics (Creatinine
      Cohort: mean age, 75 years, 42% women, 17% African American). We repeated the
      above process to assemble a secondary matched cohort of 1638 (819 pairs) patients
      with estimated glomerular filtration rate (eGFR) >=30 mL/min/1.73 m2 (eGFR
      Cohort: mean age, 75 years, 42% women, 17% African American). RESULTS: In the
      matched Creatinine Cohort, spironolactone-associated hazard ratios (95%
      confidence intervals) for all-cause mortality, heart failure readmission, and
      combined endpoint of heart failure readmission or all-cause mortality were 0.92
      (0.81-1.03), 0.87 (0.77-0.99), and 0.87 (0.79-0.97), respectively. Respective
      hazard ratios (95% confidence intervals) in the matched eGFR Cohort were 0.87
      (0.77-0.98), 0.92 (0.80-1.05), and 0.91 (0.82-1.02). CONCLUSIONS: These findings
      provide evidence of consistent, albeit modest, clinical effectiveness of
      spironolactone in older patients with HFrEF regardless of renal eligibility
      criteria used. Additional strategies are needed to improve the effectiveness of
      aldosterone antagonists in clinical practice.

PMID- 30240688
TI  - Defining Intermediate-Risk Prostate Cancer Suitable for Active Surveillance.
AB  - PURPOSE: Active surveillance (AS) for intermediate-risk prostate cancer (PCa) is
      controversial. Many AS programs are limited to grade group (GG) 1 (Gleason 6) and
      PSA<10 ng/ml. However, recent guidelines state that AS can be considered for
      limited GG2 (Gleason 3+4), despite limited data on outcomes. Our objective was to
      compare prostatectomy outcomes between subgroups of intermediate-risk versus low
      risk PCa. METHODS: We performed an observational study in the National Prostate
      Cancer Register (NPCR) of Sweden, including 98% of PCa nationwide. From 2009
      2012, 5087 men with low-risk (GG1, PSA<10, and <=cT2) and intermediate-risk PCa
      (GG2 or PSA 10-20, or T2) underwent radical prostatectomy. We compared upgrading
      and upstaging between groups, based on the UCSF Cancer of the Prostate Risk
      Assessment (CAPRA) scores and published AS criteria. Results were validated in an
      independent dataset of cases diagnosed 2013-2016. RESULTS: Men with GG1, PSA 10
      15ng/ml and PSA density <0.15 had no significant difference in upgrading and
      adverse pathology compared to low-risk PCa. PSA>15 or GG2 were associated with a
      significantly greater risk of aggressive PCa. Men with low-risk CAPRA scores (0
      2) and GG2 had almost a 3-fold increased risk of upgrading and 2-fold increased
      risk of adverse pathology compared to low-risk CAPRA GG1. CONCLUSIONS: Expanding
      the PSA threshold to 15 ng/ml for GG1 PCa would allow more men to choose AS and
      is unlikely to compromise outcomes, particularly if PSA density is low. By
      contrast, caution should be exercised in offering AS to men with PSA>15 or GG2.

PMID- 30240689
TI  - Active surveillance for localized prostate cancer. Nationwide, observational
      study.
AB  - PURPOSE: The objective of this study was to investigate nationwide survival
      outcomes in men with localized prostate cancer managed on active surveillance.
      MATERIAL AND METHODS: 936 men with localized prostate cancer initiated active
      surveillance in Denmark in 2002-2012. Kaplan-Meier estimated curative treatment
      free-, hormonal therapy-free-, castration-resistant prostate cancer-free- and
      cause-specific survival were calculated. RESULTS: Two hundred and twenty-three
      men were classified with very low-risk prostate cancer, 436 men with low-risk
      prostate cancer, 259 men with intermediate-risk prostate cancer (87% had
      favorable intermediate-risk prostate cancer), and 18 men with high-risk prostate
      cancer. The median follow-up was 7.5 years (IQR 6.1-9.1 years). Kaplan-Meier
      estimated 10-year curative treatment-free survival was 62.8% (95% CI 59.1-66.3%),
      10-year hormonal therapy-free survival was 92.2 (95% CI 89.2-94.4%), 10-year
      castration-resistant prostate cancer-free survival was 97.2% (95% CI 95.3-98.4%)
      and the 10-year cause-specific survival was 99.6% (95% CI 98.6-99.9%). Compared
      to men with low-risk prostate cancer, men with intermediate-risk prostate cancer
      had a higher curative treatment-free survival (69% vs. 56%, p = 0.008), a lower
      hormonal therapy-free survival (88% vs. 95%, p = 0.005), and similar castration
      resistant prostate cancer-free survival (95% vs. 99%, p = 0.17). CONCLUSION: In
      this nationwide cohort the 10-year cause-specific survival was similar to
      prospective active surveillance cohorts. Our study supports the use of active
      surveillance for men with localized prostate cancer - including men with
      favorable intermediate-risk characteristics.

PMID- 30240690
TI  - Female Representation on Journal Editorial Boards-Is Urology Behind the Times?

PMID- 30240691
TI  - 6-month Results of Selective Bladder Denervation in Women with Refractory
      Overactive Bladder.
AB  - PURPOSE: To report 6-month efficacy and safety outcomes with selective bladder
      denervation in women with refractory OAB. MATERIALS AND METHODS: Women with
      refractory OAB and UUI were enrolled in two prospective feasibility studies with
      the same entry criteria and received selective bladder denervation of the sub
      trigonal region containing afferent sensory nerves. Patients were followed for 6
      months and assessed for adverse events, OAB symptoms, and health-related quality
      of life measures. RESULTS: Among 35 women (mean age 66 years) enrolled in the
      study, all selective bladder denervation procedures were completed successfully.
      Over 6 months follow-up, symptom improvement based on 3-day bladder diaries was
      59% for UUI (p<0.001), 59% for UI (p<0.001), 39% for urgency (p<0.001), 9% for
      urinary frequency (p=0.01), and 27% for the total urgency and frequency score
      (p<0.001), with the majority of this treatment benefit realized in the first
      month. Clinical success (>=50% reduction in UUI) was 70%, treatment benefit was
      reported in 75% of patients, and the dry/cure rate was 27%. Statistically
      significant improvements over 6 months were identified on Symptom Bother and
      Health-related Quality of Life scales on the OAB-q, and on all KHQ domains except
      General Health Perception. Device- or procedure-related adverse events were
      reported in 6 (17%) patients. CONCLUSIONS: Pooled results of two prospective
      feasibility studies suggest that selective bladder denervation is a promising
      minimally invasive treatment option for women with refractory OAB.

PMID- 30240692
TI  - Characterization of a Standardized Postoperative Radiographic and Functional
      Voiding Trial after One-Stage Bulbar Ventral Onlay Buccal Mucosal Graft
      Urethroplasty and the Impact on Stricture Recurrence-Free Survival.
AB  - PURPOSE: To characterize a standardized postoperative radiographic and functional
      voiding trial and determine its impact on outcomes after substitution
      urethroplasty. MATERIALS AND METHODS: This is an observational, monocentric study
      of men undergoing one-stage ventral onlay buccal mucosal graft urethroplasty for
      bulbar urethral stricture between 01/2009 and 12/2016. Patients were stratified
      by voiding trial success versus failure (radiographic: extravasation or residual
      narrowness; functional: postvoid residual volume >100ml) 21 days postoperatively.
      Endpoints were voiding trial failure and recurrence-free survival. Regression
      models were created to determine risk factors of voiding trial failure and to
      evaluate the impact of voiding trial failure on recurrence. RESULTS: Of 513 men,
      437(85.2%) and 76(14.8%) succeeded and failed at voiding trial, respectively. Of
      the latter, 54(71.1%) showed evidence of extravasation, and 22(28.9%) had
      residual narrowness or failed functionally. In multivariable logistic regression
      analyses, no preoperative predictor of voiding trial failure was found (all
      P>0.05). At a median follow-up of 32 months, both Kaplan-Meier analyses (log-rank
      test: P=0.033) and multivariable Cox regression analyses (hazard ratio=1.86;
      P=0.037) revealed an association of voiding trial failure and stricture
      recurrence. When further stratifying voiding trial failure, residual narrowness
      or functional failure (hazard ratio=4.60; P<0.001) but not extravasation (hazard
      ratio=1.08; P=0.9) was a risk factor of recurrence. Limitations include the
      retrospective assessment of investigated endpoints. CONCLUSIONS: Residual
      narrowness or functional failure at an early voiding trial after buccal mucosal
      graft urethroplasty may predict stricture recurrence. Identification of
      intraoperative complexity factors predicting initial voiding trial failure might
      be a key to identify those individuals who recur early.

PMID- 30240693
TI  - Berberine modulates ASK1 signaling mediated through TLR4/TRAF2 via upregulation
      of miR-23a.
AB  - The current study was designed to explore the underlying therapeutic effect of
      berberine (BBR), an alkaloid compound against LPS (1 MUg/ml)/TNFalpha (10 ng/ml)
      mediated apoptosis signal-regulating kinase 1 (ASK1) signaling in RAW 264.7
      macrophages and adjuvant-induced arthritic synovial macrophages (AA-SM) with
      relation to miR-23a levels. LPS and TNFalpha stimulation abrogated the expression
      of miR-23a resulting in TLR4/TRAF2 mediated ASK1 activation and downstream
      phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). BBR (25-75
      MUM) treatment ameliorated the gene expression levels of TLR4, TRAF2, TNFalpha,
      IL-6, and IL-23 through the upregulation of miR-23a. Subsequently, BBR suppressed
      the levels of TLR4/TRAF2 mediated phosphorylation of ASK1/p38 and attenuated the
      expression of various pro-inflammatory cytokines (TNFalpha, IL-6 & IL-23) in RAW
      264.7 macrophages and AA-SM cells. BBR was able to counteract these factors
      through activation of miR-23a levels in LPS/TNFalpha stimulated RAW 264.7
      macrophages and AA-SM cells. NQDI1 (30 MUM) treatment inhibited ASK1 activation
      resulting in basal levels of miR-23a, owing to the conclusion that ASK1
      activation downregulates miR-23a levels inside the cells. Overall, our current
      findings predict that BBR is a potential candidate for therapeutic targeting of
      TLR4/TRAF2 mediated ASK1 activation in inflammatory and in RA pathogenesis
      possibly through post-transcriptional gene silencing via upregulation of miR-23a.

PMID- 30240694
TI  - The epidemiologic evidence for elongate mineral particle (EMP)-related human
      cancer risk.
AB  - Epidemiologic research on the role of fibers and other elongate mineral particles
      (EMP) and human diseases including cancers has generated a large body of
      literature over the last decades: nevertheless, there remain some questions for
      which the scientific community appears unable to reach consensus. Reasons for
      genuine differences in opinion include (i) ways in which exposures have been
      classified; (ii) methodological limitations of the available studies, (iii)
      criteria for the interpretation of study results, including potential underlying
      biological mechanisms, and (iv) methodology for integrating the evidence. Various
      approaches have been proposed in recent years to address these issues, which will
      be illustrated using examples from asbestos, talc, taconite, synthetic mineral
      fibers and silicon carbide, with emphasis on potential carcinogenic effects.
      Potential solutions include improved exposure and outcome assessment - including
      use of biomarkers and other molecular approaches, consideration of potential
      confounding and other sources of bias, implementation of guidelines for study
      quality assessment and evidence evaluation and integration.

PMID- 30240695
TI  - Characterization of asbestiform glaucophane-winchite in the Franciscan Complex
      blueschist, northern Diablo Range, California.
AB  - This paper presents a geologic and mineralogical investigation of asbestiform
      amphibole from blueschist in the Diablo Range, northern California. The analysis
      of fibers in air samples shows that the dominant blueschist amphibole composition
      ranges from glaucophane to subordinate winchite. In outcrop, blueschist amphibole
      exhibits a velvety luster, and its occurrence ranges from crosscutting veins to
      highly deformed foliated and lineated tectonites. TEM and SEM photographs reveal
      a highly fibrous habit typically associated with asbestiform amphiboles.
      Dimensional analysis reveals a mean fiber width of 0.27 MUm, and lengths and
      aspect ratios are shorter than reported for commercially exploitable asbestos,
      with a mean length of 2.8 MUm and mean aspect ratio of 11.5. The data are
      consistent with other research showing that the width population of fibers, and
      not length or aspect ratio, is the key indicator of the asbestiform habit. The
      blueschist data are compared to non-asbestiform hornblende amphibole in granitic
      rocks. The fiber concentration of the hornblende (458 MFG) is low compared to the
      blueschist amphibole (107,880 MFG) and chrysotile in serpentinite (196,066 MFG),
      indicating that under similar conditions, the exposure potential from cleaved
      particles could be several orders of magnitude lower than from asbestiform
      particles. The asbestiform habit of glaucophane is present at two other locations
      in the Franciscan Complex, suggesting that asbestiform blueschist amphibole may
      be characteristic within blueschist terranes, and rock formations containing
      asbestiform amphibole may be more common and widespread than previously assumed.

PMID- 30240696
TI  - Selenium-lentinan inhibits tumor progression by regulating epithelial-mesenchymal
      transition.
AB  - BACKGROUND: Selenium supplementation can be used to treat tumors. However,
      inorganic selenium is highly toxic, and natural organic selenium is extremely
      rare. Polysaccharides can improve drug bioavailability and targeting. Lentinan is
      a polysaccharide that has been approved as an anti-cancer drug in Japan and
      China. METHODS: Lentinan, an antitumor polysaccharide extracted from Lentinus
      edodes, was conjugated with seleninic acid to be transformed into ester (Se
      lentinan) and utilized as drug carrier. The enhancement of the anti-tumor effects
      of Se-lentinan was evaluated by cell viability, cell cycle, migration, and
      transwell assays and animal xenograft models. The effects of Se-lentinan on the
      expression levels of epithelial-mesenchymal transition (EMT) markers were
      determined through immunofluorescence, Western blot, and immunohistochemistry
      analyses. RESULTS: Se-lentinan inhibited the invasiveness of B16-BL6 and HCT-8
      cells by suppressing EMT. In vivo, Se-lentinan significantly inhibited tumor
      growth and metastasis of the transplanted melanoma and colon cancer cells and
      showed less toxicity than sodium selenite. Moreover, Se-lentinan reduced the
      accumulation of selenium in the liver and kidney tissues of mice and exhibited
      low organ toxicity. CONCLUSION: The antitumor activity of selenium was enhanced
      greatly, and its side effects were reduced with the use of lentinan as drug
      carrier.

PMID- 30240698
TI  - Marked Changes in Lamellar Granule and Trans-Golgi Network Structure Occur During
      Epidermal Keratinocyte Differentiation.
AB  - Epidermal lamellar granules (LGs) transport various lipids, proteins and protein
      inhibitors from the trans-Golgi network (TGN) to the extracellular space, and
      play an important role in skin barrier formation. We elucidated the three
      dimensional (3D) structure of LGs and the TGN in normal human skin by focused ion
      beam scanning electron microscopy (FIB-SEM). Reconstructed FIB-SEM 3D images
      revealed that the overall LG structure changed from vesicular to reticular within
      the second layer of the stratum granulosum. Furthermore, the TGN was well
      developed within this layer and spread through the cytoplasm with branched,
      tubular structures that connected to LGs. Our study reveals the unique overall 3D
      structure of LGs and the TGN within the cells of the epidermis, and provides the
      basis for an understanding of the skin barrier formation.

PMID- 30240699
TI  - Identification and sequence analysis of two novel cryptic plasmids isolated from
      the vaginal mucosa of South African women.
AB  - The vaginal mucosa is dominated by Gram positive, rod shaped lactobacilli which
      serve as a natural barrier against infection. In both healthy- and bacterial
      vaginosis (BV)-infected women Lactobacillus crispatus and Lactobacillus jensenii
      have been found to be the predominant Lactobacillus species. Many studies have
      been conducted to assess factors influencing lactobacilli dominance in the
      vaginal microbiome. In the present study two plasmids, pLc4 and pLc17, isolated
      from vaginal Lactobacillus strains of both healthy and BV-infected women were
      characterized. The smaller plasmid, pLc4 (4224 bp), was detected in both L.
      crispatus and L. jensenii strains, while pLc17 was only detected in L. crispatus.
      Based on its nucleotide sequence pLc4 appears highly novel, with its replication
      protein having 44% identity to the replication initiation protein of pSMQ173b_03.
      Phylogenetic analysis with other Rolling Circle Replication plasmids confirmed
      that pLc4 shows a low degree of similarity to these plasmids. Plasmid pLc17
      (16,663 bp) appears to carry both a RCR replicon and a theta replicon, which is
      rare in naturally occurring plasmids. pLc4 was maintained at a high copy number
      of 29, while pLc17 appears to be a medium copy number plasmid maintained at 11
      copies per chromosome. While sequence analysis is a valuable tool to study
      cryptic plasmids, further function-based analysis will be required in order to
      fully elucidate the role of these plasmids within the vaginal milieu.

PMID- 30240697
TI  - Bisphenol A (BPA) and bisphenol S (BPS) alter the promoter activity of the ABCB1
      gene encoding P-glycoprotein in the human placenta in a haplotype-dependent
      manner.
AB  - Exposure to bisphenols (BPA and BPS) during pregnancy can significantly affect
      fetal development and increase risk of adverse health consequences, however the
      underlying mechanisms are not fully elucidated. In human placenta, the efflux
      transporter P-glycoprotein (P-gp), encoded by the ABCB1 gene, extrudes its
      substrates from the trophoblasts back into the maternal circulation. Alterations
      in levels of placental P-gp could therefore significantly affect fetal exposure
      to xenobiotics that are P-gp substrates. The ABCB1 promoter contains many single
      nucleotide polymorphisms (SNPs). In the genome, SNPs are not arrayed as
      independent variants but as combinations forming defined haplotypes. Recently, we
      determined the haplotype sequences encompassing the ABCB1 promoter SNPs and found
      that promoter haplotypes differentially affect ABCB1 promoter activity. Here we
      investigate the effect of BPA and BPS on ABCB1 promoter activity by testing the
      hypothesis that BPA and BPS exposure affect ABCB1 promoter activity in a
      haplotype-dependent manner. Our data indicate that acute exposure to 50 nM BPA
      induced a significant haplotype-dependent increase in ABCB1 promoter activity (P
      < .05). However, acute exposure to 0.5 nM BPS induced a significant decrease (P <
      .05) in promoter activity that was haplotype-dependent. Chronic exposure to BPA
      and BPS individually (5 nM and 0.3 nM, respectively) or as a mixture (5 nM
      BPA:1.5 nM BPS) induced significant haplotype-dependent increases (P < .01) in
      ABCB1 promoter activity. Our data indicate that BPA and BPS significantly alter
      ABCB1 promoter activity in a haplotype- and exposure type- dependent manners.
      Such alteration could significantly impact placental P-gp levels and alter fetal
      exposure to many therapeutic and environmental xenobiotics.

PMID- 30240700
TI  - Impact of plasmid interactions with the chromosome and other plasmids on the
      spread of antibiotic resistance.
AB  - Naturally occurring plasmids have medical importance given that they frequently
      code for virulence or antibiotic resistance. In many cases, plasmids impose a
      fitness cost to their hosts, meaning that the growth rate of plasmid-bearing
      cells is lower than that of plasmid-free cells. However, this does not fit with
      the fact that plasmids are ubiquitous in nature nor that plasmids and their hosts
      adapt to each other very fast - as has been shown in laboratory evolutionary
      assays. Even when plasmids are costly, they seem to largely interact in such a
      way that the cost of two plasmids is lower than the cost of one of them alone.
      Moreover, it has been argued that transfer rates are too low to compensate for
      plasmid costs and segregation. Several mechanisms involving interactions between
      plasmids and other replicons could overcome this limitation, hence contributing
      to the maintenance of plasmids in bacterial populations. We examine the
      importance of these mechanisms from a clinical point of view, particularly the
      spread of antibiotic resistance genes.

PMID- 30240701
TI  - Severe bronchiolitis profiles and risk of recurrent wheeze by age 3 years.
AB  - BACKGROUND: A better understanding of bronchiolitis heterogeneity might help
      clarify its relationship with the development of recurrent wheezing and asthma.
      OBJECTIVES: We sought to identify severe bronchiolitis profiles using a
      clustering approach and to investigate for the first time their association with
      allergy/inflammatory biomarkers, nasopharyngeal microbiota, and development of
      recurrent wheezing by age 3 years. METHODS: We analyzed data from a prospective,
      17-center US cohort study of 921 infants (age <1 year) hospitalized with
      bronchiolitis (2011-2014 winters) with posthospitalization follow-up. Severe
      bronchiolitis profiles at baseline (hospitalization) were determined by using
      latent class analysis based on clinical factors and viral etiology. Blood
      biomarkers and nasopharyngeal microbiota profiles were determined by using
      samples collected within 24 hours of hospitalization. Recurrent wheezing by age 3
      years was defined based on parental report of breathing problem episodes after
      discharge. RESULTS: Three severe bronchiolitis profiles were identified: profile
      A (15%), which was characterized by a history of breathing problems/eczema during
      infancy and non-respiratory syncytial virus (mostly rhinovirus) infection;
      profile B (49%), which has the largest probability of respiratory syncytial virus
      infection and resembled classic respiratory syncytial virus-induced
      bronchiolitis; and profile C (36%), which was composed of the most severely ill
      group. Profile A infants had higher eosinophil counts, higher cathelicidin
      levels, and increased proportions of Haemophilus-dominant or Moraxella-dominant
      microbiota profiles. Compared with profile B, we observed significantly increased
      risk of recurrent wheezing in children with profile A (hazard ratio, 2.64; 95%
      CI, 1.90-3.68) and, to a lesser extent, with profile C (hazard ratio, 1.51; 95%
      CI, 1.14-2.01). CONCLUSION: Although longer follow-up is needed, our results
      might help identify, among children hospitalized for bronchiolitis, subgroups
      with particularly increased risk of asthma.

PMID- 30240703
TI  - Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation
      in offspring through regulatory T cells.
AB  - BACKGROUND: Transmaternal exposure to tobacco, microbes, nutrients, and other
      environmental factors shapes the fetal immune system through epigenetic
      processes. The gastric microbe Helicobacter pylori represents an ancestral
      constituent of the human microbiota that causes gastric disorders on the one hand
      and is inversely associated with allergies and chronic inflammatory conditions on
      the other. OBJECTIVE: Here we investigate the consequences of transmaternal
      exposure to H pylori in utero and/or during lactation for susceptibility to viral
      and bacterial infection, predisposition to allergic airway inflammation, and
      development of immune cell populations in the lungs and lymphoid organs. METHODS:
      We use experimental models of house dust mite- or ovalbumin-induced airway
      inflammation and influenza A virus or Citrobacter rodentium infection along with
      metagenomics analyses, multicolor flow cytometry, and bisulfite pyrosequencing,
      to study the effects of H pylori on allergy severity and immunologic and
      microbiome correlates thereof. RESULTS: Perinatal exposure to H pylori extract or
      its immunomodulator vacuolating cytotoxin confers robust protective effects
      against allergic airway inflammation not only in first- but also second
      generation offspring but does not increase susceptibility to viral or bacterial
      infection. Immune correlates of allergy protection include skewing of regulatory
      over effector T cells, expansion of regulatory T-cell subsets expressing CXCR3 or
      retinoic acid-related orphan receptor gammat, and demethylation of the forkhead
      box P3 (FOXP3) locus. The composition and diversity of the gastrointestinal
      microbiota is measurably affected by perinatal H pylori exposure. CONCLUSION: We
      conclude that exposure to H pylori has consequences not only for the carrier but
      also for subsequent generations that can be exploited for interventional
      purposes.

PMID- 30240702
TI  - Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through
      keratinocyte IL-1alpha release.
AB  - BACKGROUND: Atopic dermatitis (AD) is associated with epidermal barrier defects,
      dysbiosis, and skin injury caused by scratching. In particular, the barrier
      defective epidermis in patients with AD with loss-of-function filaggrin mutations
      has increased IL-1alpha and IL-1beta levels, but the mechanisms by which IL
      1alpha, IL-1beta, or both are induced and whether they contribute to the aberrant
      skin inflammation in patients with AD is unknown. OBJECTIVE: We sought to
      determine the mechanisms through which skin injury, dysbiosis, and increased
      epidermal IL-1alpha and IL-1beta levels contribute to development of skin
      inflammation in a mouse model of injury-induced skin inflammation in filaggrin
      deficient mice without the matted mutation (ft/ft mice). METHODS: Skin injury of
      wild-type, ft/ft, and myeloid differentiation primary response gene-88-deficient
      ft/ft mice was performed, and ensuing skin inflammation was evaluated by using
      digital photography, histologic analysis, and flow cytometry. IL-1alpha and IL
      1beta protein expression was measured by means of ELISA and visualized by using
      immunofluorescence and immunoelectron microscopy. Composition of the skin
      microbiome was determined by using 16S rDNA sequencing. RESULTS: Skin injury of
      ft/ft mice induced chronic skin inflammation involving dysbiosis-driven
      intracellular IL-1alpha release from keratinocytes. IL-1alpha was necessary and
      sufficient for skin inflammation in vivo and secreted from keratinocytes by
      various stimuli in vitro. Topical antibiotics or cohousing of ft/ft mice with
      unaffected wild-type mice to alter or intermix skin microbiota, respectively,
      resolved the skin inflammation and restored keratinocyte intracellular IL-1alpha
      localization. CONCLUSIONS: Taken together, skin injury, dysbiosis, and filaggrin
      deficiency triggered keratinocyte intracellular IL-1alpha release that was
      sufficient to drive chronic skin inflammation, which has implications for AD
      pathogenesis and potential therapeutic targets.

PMID- 30240704
TI  - Designing salicylaldehyde isonicotinoyl hydrazones as Cu(II) ionophores with
      tunable chelation and release of copper for hitting redox Achilles heel of cancer
      cells.
AB  - Higher levels of copper, reduced glutathione (GSH) and reactive oxygen species
      (ROS) observed in cancer cells than in normal cells, favor the idea of developing
      copper ionophores as prooxidative anticancer agents (PAAs) to hit the altered
      redox homeostasis (redox Achilles heel) of cancer cells. In this work, we used
      salicylaldehyde isonicotinoyl hydrazone (SIH-1) as a basic scaffold to design
      Cu(II) ionophores with tunable chelation and release of Cu(II) by introducing
      electron-withdrawing nitro and electron-donating methoxyl groups in the para
      position to phenolic hydroxyl, or by blocking the phenolic hydroxyl site using
      methyl. These molecules were used to probe how chelation and release of copper
      influence their ionophoric role and ability to target redox Achilles heel of
      cancer cells. Among these molecules, SIH-1 was identified as the most potent
      Cu(II) ionophore to kill preferentially HepG2 cells over HUVEC cells, and also
      superior to clioquinol, a copper ionophore evaluated in clinical trials, in terms
      of its relatively higher cytotoxicity and better selectivity. Higher oxidative
      potential, despite of lower stability constant, of the Cu(II) complex formed by
      SIH-1 than by the other molecules, is responsible for its stronger ability in
      releasing copper by GSH, inducing redox imbalance and triggering mitochondria
      mediated apoptosis of HepG2 cells. This work gives useful information on how to
      design copper ionophores as PAAs for selective killing of cancer cells.

PMID- 30240705
TI  - Measuring the ability of HIV-specific antibodies to mediate trogocytosis.
AB  - Antibody Fc effector functions contribute to HIV control and have been implicated
      in the partial efficacy seen in the RV144 vaccine trial. Fc-mediated trogocytosis
      has been previously described for anti-cancer antibodies and results in the
      removal of membrane fragments from target cells. Here we developed a flow
      cytometry-based assay which measures the transfer of membrane fragments from a
      gp120-coated CD4+ lymphocytic cell line (CEM.NKR-CCR5 cells stained with a
      membrane dye PKH26) to monocytic cells (THP-1 cells stained with CFSE). We showed
      that this transfer occurred rapidly, within 1 h, and was mediated through
      engagement of the FcgammaRIIa/b receptors on the THP-1 cells. HIV-specific IgG as
      well as gp120 and CD4 could be detected on the surface of THP-1 cells in a
      process that we demonstrated was distinct from phagocytosis. Furthermore, while
      the THP-1 effector cells remained intact following the receipt of new membrane
      proteins, the viability of the target CEM.NKR-CCR5 cells decreased over time.
      Analysis of HIV-specific plasma revealed that antibodies with trogocytic activity
      were common in acute and chronic HIV infection but were higher in individuals
      with broadly neutralizing antibody responses We also examined trogocytosis
      mediated by broadly neutralizing antibodies (bNAbs) targeting multiple epitopes
      on the BG505.SOSIP.664 trimer and show that levels of binding correlated with the
      trogocytosis score. Overall, our data describe a new antiviral Fc effector
      function mediated by HIV-specific antibodies that could be harnessed for
      vaccination and cure strategies.

PMID- 30240706
TI  - Inactivation of Magel2 suppresses oxytocin neurons through synaptic excitation
      inhibition imbalance.
AB  - Prader-Willi and the related Schaaf-Yang Syndromes (PWS/SYS) are rare
      neurodevelopmental disorders characterized by overlapping phenotypes of high
      incidence of autism spectrum disorders (ASD) and neonatal feeding difficulties.
      Based on clinical and basic studies, oxytocin pathway defects are suggested to
      contribute disease pathogenesis but the mechanism has been poorly understood.
      Specifically, whether the impairment in oxytocin system is limited to
      neuropeptide levels and how the functional properties of broader oxytocin neuron
      circuits affected in PWS/SYS have not been addressed. Using cell type specific
      electrophysiology, we investigated basic synaptic and cell autonomous properties
      of oxytocin neurons in the absence of MAGEL2; a hypothalamus enriched ubiquitin
      ligase regulator that is inactivated in both syndromes. We observed significant
      suppression of overall ex vivo oxytocin neuron activity, which was largely
      contributed by altered synaptic input profile; with reduced excitatory and
      increased inhibitory currents. Our results suggest that dysregulation of oxytocin
      system goes beyond altered neuropeptide expression and synaptic excitation
      inhibition imbalance impairs overall oxytocin pathway function.

PMID- 30240707
TI  - Co-expulsion of Ascaridia galli and Heterakis gallinarum by chickens.
AB  - Worm expulsion is known to occur in mammalian hosts exposed to mono-species
      helminth infections, whilst this phenomenon is poorly described in avian hosts.
      Mono-species infections, however, are rather rare under natural circumstances.
      Therefore, we quantified the extent and duration of worm expulsion by chickens
      experimentally infected with both Ascaridia galli and Heterakis gallinarum, and
      investigated the accompanying humoral and cell-mediated host immune responses in
      association with population dynamics of the worms. Results demonstrated the
      strong co-expulsion of the two ascarid species in three phases. The expulsion
      patterns were characterized by non-linear alterations separated by species
      specific time thresholds. Ascaridia galli burden decreased at a daily expulsion
      rate (e) of 4.3 worms up to a threshold of 30.5 days p.i., followed by a much
      lower second expulsion rate (e = 0.46), which resulted in almost, but not
      entirely, complete expulsion. Heterakis gallinarum was able to induce reinfection
      within the experimental period (9 weeks). First generation H. gallinarum worms
      were expelled at a daily rate of e = 0.8 worms until 36.4 days p.i., and
      thereafter almost no expulsion occurred. Data on both humoral and tissue-specific
      cellular immune responses collectively indicated that antibody production in
      chickens with multispecies ascarid infections is triggered by Th2 polarisation.
      Local Th2 immune responses and mucin-regulating genes are associated with the
      regulation of worm expulsion. In conclusion, the chicken host is able to
      eliminate the vast majority of both A. galli and H. gallinarum in three distinct
      phases. Worm expulsion was strongly associated with the developmental stages of
      the worms, where the elimination of juvenile stages was specifically targeted. A
      very small percentage of worms was nevertheless able to survive, reach maturity
      and induce reinfection if given sufficient time to complete their life cycle.
      Both humoral and local immune responses were associated with worm expulsion.

PMID- 30240708
TI  - A comparative study of skin irritation caused by novel bis-quaternary ammonium
      compounds and commonly used antiseptics by using cell culture methods.
AB  - New bis-quaternary ammonium compounds (bis-QACs) 3-(3-hydroxy-2-(hydroxymethyl)-2
      {[(1-dodecylpyridinium-3-yl)oxy]methyl}propoxy)-1-dodecylpyridinium dibromide
      (3HHDMP-12) and 3,3'-[1,4-phenylenebis(oxy)]bis(1-dodecylpyridinium) dibromide
      (3PHBO-12) were compared with commonly-used antiseptics such as benzalkonium
      chloride (BAC), octenidine dihydrochloride (OCT), chlorhexidine digluconate (CHG)
      and polyhexamethylene biguanide (PHMB), to evaluate their potential to cause skin
      irritation. The cytotoxicity of these compounds in various cultured cells, as
      well as their effect on the expression of inflammatory cytokine genes such as IL
      1alpha were evaluated. The cytotoxic effect of these bis-QACs on several types of
      human-derived cells was lower than that of common quaternary ammonium compounds
      (BAC and OCT), although the bis-QACs showed higher cytotoxicity than the
      biguanide-based compounds (CHG and PHMB). In addition, IL-1alpha mRNA expression
      was more strongly induced by BAC and OCT than by the new bis-QACs, at
      concentrations below the IC50 obtained in normal human epidermal keratinocytes.
      Furthermore, even at the actual therapeutic concentration, the new bis-QACs did
      not alter inflammatory cytokine mRNA expression or IL-1alpha secretion as
      demonstrated using the reconstructed human epidermis model LabCyte EPI-MODEL. The
      results suggested that the potential of 3PHBO-12 and 3HHDMP-12 to induce skin
      irritation is comparable to or less than that of existing antiseptics, and these
      bis-QACs may be useful antiseptics with few side effects.

PMID- 30240709
TI  - Interactions between oxidative stress, autophagy and apoptosis in A549 cells
      treated with aged black carbon.
AB  - After emitted from incomplete combustion of fossil fuels and biomass, ambient
      black carbon (BC) was then undergone photochemical oxidization processes in the
      air to form aged BC particles, also called oxidized BC (OBC). This study aimed to
      investigate the interactions between oxidative stress, autophagy and apoptosis
      induced by OBC in A549 cells and to explore associated molecular mechanisms.
      First, OBC could stimulate oxidative stress, autophagy and apoptosis dose
      dependently, as evidenced by increased intercellular reactive oxygen species
      (ROS) levels, up-regulated autophagosome markers (light chain 3, LC3), and
      elevated apoptosis rate. Inhibitors of oxidative stress (N-acetylcysteine, NAC),
      autophagy (bafilomycin A1, Baf) and apoptosis (Z-DEVD-FMK) were used to
      investigate their interactions. NAC pretreatment could significantly reduce
      autophagy and apoptosis. Additionally, pretreatment with Baf or Z-DEVD-FMK could
      also significantly suppress the other two biological effects. Furthermore, OBC up
      regulated the expressions of DNA-dependent protein kinase catalytic subunit (DNA
      PKcs), phosphorylated protein kinase B (Akt) and mammalian target of rapamycin
      (mTOR). The Akt inhibitor (MK-2206) significantly reduced both autophagy and
      apoptosis. Taken together, dual-direction regulation existed between each two of
      oxidative stress, autophagy, and apoptosis in A549 cells exposed to OBC. In
      addition, the autophagy process is modulated by the PI3K/Akt pathway regardless
      of mTOR activity.

PMID- 30240710
TI  - Autopsy findings of ectodermal dysplasia and sex development disorder in a fetus
      with 19q12q13 microdeletion.
AB  - A 5,6 Mb de novo 19q12-q13.12 interstitial deletion was diagnosed prenatally by
      array-comparative genomic hybridization in a 26 weeks male fetus presenting with
      intra-uterine growth retardation, left clubfoot, atypical genitalia and
      dysmorphic features. Autopsic examination following termination of pregnancy
      identified a severe disorder of sex development (DSD) including hypospadias,
      micropenis, bifid scrotum and right cryptorchidism associated with signs of
      ectodermal dysplasia: scalp hypopigmentation, thick and frizzy hair, absence of
      eyelashes, poorly developed nails and a thin skin with prominent superficial
      veins. Other findings were abnormal lung lobation and facial dysmorphism. This
      new case of DSD with a 19q12q13 deletion expands the phenotypic spectrum
      associated with this chromosomal rearrangment and suggests that WTIP is a strong
      candidate gene involved in male sex differentiation.

PMID- 30240711
TI  - Comparative mitochondrial genome analysis of Grammodes geometrica and other
      noctuid insects reveals conserved mitochondrial genome organization and
      phylogeny.
AB  - The mitochondrial genome (mitogenome) plays an important role in revealing
      molecular evolution. In this study, the complete mitogenome of Grammodes
      geometrica (G. geometrica) (Lepidoptera: Erebidae) was sequenced and
      characterized. The nucleotide composition of the genome is highly A + T biased,
      accounting for 80.49%. Most protein-coding genes (PCGs) are initiated by ATN
      codons except for the cytochrome oxidase subunit 1 (cox1) gene, which was
      initiated by CGA. The order and orientation of genes with the order trnM-trnI
      trnQ-nad2 is a typical rearrangement compared with those ancestral insects in
      which trnM is located between trnQ and nad2. Most tRNA genes were folded into the
      typical cloverleaf structure except for trnS1 (AGN). The A + T-rich region
      contains the conserved motif "ATAGA" followed by a 19 bp poly-T stretch, which
      was also observed in other Noctuoidea species. In addition, we reconstructed
      phylogenetic trees among the nucleotide alignments of five families of Noctuoidea
      species except the Oenosandridae. Finally, we achieved a well-supported tree,
      which showed that G. geometrica belongs to the Erebidae family. Moreover, the
      relationships at the family-level can be displayed as follows: (Notodontidae +
      (Erebidae + (Nolidae + (Euteliidae + Noctuidae)))).

PMID- 30240712
TI  - The effects of cardiomyopathy-associated mutations in the head-to-tail overlap
      junction of alpha-tropomyosin on its properties and interaction with actin.
AB  - Tropomyosin (Tpm) plays a crucial role in the regulation of muscle contraction by
      controlling actin-myosin interaction. Tpm coiled-coil molecules bind each other
      via overlap junctions of their N- and C-termini and form a semi-rigid strand that
      binds the helical surface of an actin filament. The high bending stiffness of the
      strand is essential for high cooperativity of muscle regulation. Point mutations
      M8R and K15N in the N-terminal part of the junction and the A277V one in the C
      terminal part are associated with dilated cardiomyopathy, while the M281T and
      I284V mutations are related to hypertrophic cardiomyopathy. To reveal molecular
      mechanism(s) underlying these pathologies, we studied the properties of
      recombinant Tpm carrying these mutations using several experimental approaches
      and molecular dynamic simulation of the junction. The M8R and K15N mutations
      weakened the interaction between the N- and C-termini of Tpm in the overlap
      junction and reduced the Tpm affinity for actin. These changes possibly led to a
      reduction in the regulation cooperativity. The C-terminal mutations caused only
      small and controversial changes in properties of Tpm and its complex with actin.
      Their involvement in disease phenotype is possibly caused by interaction with
      other sarcomere proteins.

PMID- 30240713
TI  - Cloning, expression and enzymatic characteristics of a 2-Cys peroxiredoxin from
      Antarctic sea-ice bacterium Psychrobacter sp. ANT206.
AB  - Peroxiredoxin (Prx, EC 1.11.1.15) is a family of the thiol-dependent antioxidant
      enzyme. In this study, a cold-adapted Prx gene from Antarctic psychrophilic
      bacterium Psychrobacter sp. ANT206 (PsPrx) consisted of an open reading frame
      (ORF) of 567 bp was cloned. Amino acid sequence analysis revealed that PsPrx
      contained one catalytic site (Thr45, Cys48 and Arg121) and could be categorized
      as a typical 2-Cys Prx. Compared with the mesophilic StPrx, PsPrx with a reduced
      amount of hydrogen bonds and salt bridges and other characteristics, may be
      responsible for its enzymatic stability and flexibility at low temperature. The
      recombinant PsPrx (rPsPrx) was purified to homogeneity by Ni-NTA and its
      enzymatic characterization was described. Interestingly, rPsPrx exhibited the
      maximum activity at 30  degrees C and remained 42.6% of its maximum activity at 0
      degrees C. rPsPrx was a salt-tolerance enzyme that showed 42.2% of its maximum
      activity under 2.5 M NaCl. The kinetic parameters of different substrates
      revealed that it could efficiently catalyze the peroxides, especially H2O2 and t
      BOOH (tert-butyl hydroperoxide). Moreover, rPsPrx exhibited the ability to
      protect super-coiled DNA from oxidative damage. These results indicated that
      rPsPrx has special catalytic properties and may be a promising candidate for food
      and industrial applications.

PMID- 30240714
TI  - Chemical modification of alginate with cysteine and its application for the
      removal of Pb(II) from aqueous solutions.
AB  - It has been synthesized, characterized and tested a new biomaterial AlgS (sodium
      alginate functionalized with cysteine) to remove Pb(II) in aqueous media. The
      maximum Pb(II)-sorption capacity of AlgS (Qmax = 770 mg.g-1) is between almost
      two and nine times higher than other alginate-materials reported in the
      literature. Techniques, such as TGA/DSC, SEM/EDS, BET, FTIR, UV-Vis, XRD and 13C
      solid state-NMR have been used to study the chemical-modification of alginate at
      oxidation and aminofication stages. The formation of the imine intermediate
      (C=N), after 24 h of reaction was identified by a UV band at 348 nm. Typical IR
      bands of AlgS were identified at 2970, 955, 949 and 1253 cm-1 which are
      associated to CH, SPb, SH and CN stretching vibrations, respectively. 13C solid
      state-NMR spectra of AlgS, show peaks at 33-38 ppm and 55-60 ppm associate to
      delta (HS-CH2-) of cysteine and delta (CN) respectively. The DeltaH degrees  and
      DeltaG degrees  negative values for Pb(II) sorption indicate that it is an
      exothermic process and occur spontaneously. Finally, it was found that the Pb(II)
      sorption on AlgS is significantly affected by the presence of cationic (Na+, Mg2+
      and Al3+) and anionic (Cl-, NO3-) co-ions.

PMID- 30240715
TI  - Identification of four type I IFNs from Japanese eel with differential expression
      properties and Mx promoter inducibility.
AB  - Type I IFNs are a family of cytokines with antiviral, anti-proliferative and
      immune-modulatory functions. In this study, four type I IFNs (termed AjIFN1-4)
      have been cloned from the Japanese eel, Anguilla japonica. The open reading
      frames of AjIFN1-4 are 552, 534, 546 and 561 bp in length, encoding 183, 177,
      181, and 186 amino acids (aa), respectively. Sequence comparison and phylogenetic
      analysis results revealed that AjIFN1 and AjIFN2 belong to group one (2C
      containing) IFNs, while AjIFN3 and AjIFN4 belong to group two (4C-containing)
      IFNs. Syntenic comparison showed that chromosome block duplication and
      rearrangement events might have occurred at IFN loci in different teleost
      lineages. Expression analysis revealed the rapid induction of AjIFNl and AjIFN2
      in response to poly I:C stimulation, while AjIFN3 and AjIFN4 were predominantly
      expressed at later time points. Two Mx promoter reporter assays were conducted to
      assess the Mx-inducing capability of AjIFN1-4. It is shown that the
      overexpression of AjIFN1-4 all promoted the luciferase activity of MxB reporter,
      but the activity of MxC reporter increased only in cells transfected with AjIFN1.
      Collectively, it is suggested that teleost IFNs were evolved independently in
      different lineages of fish and may function differently in teleost antiviral
      immunity.

PMID- 30240716
TI  - Synesthesia improves sensory memory, when perceptual awareness is high.
AB  - Empirical evidence suggests that synesthesia is associated with enhanced sensory
      processing. A separate body of empirical literature suggests that synesthesia is
      linked to a specific profile of enhanced episodic and working memory performance.
      However, whether sensory (iconic) memory performance is also affected by
      synesthesia remains unknown. Therefore, we tested 22 grapheme-color synesthetes
      and compared their performance in a partial-report paradigm with 22 individually
      matched non-synesthete controls. Participants were briefly presented with a
      circular-letter array and required to report the identity of the letter at a
      probed target location after various delays. Furthermore, they were required to
      indicate the subjective clarity of the target letter after every trial. The
      results suggest that sensory memory performance is enhanced in synesthesia, but
      only when subjective clarity of the target letter is high. Additional exploratory
      analyses revealed that synesthetic consistency, which is widely used to confirm
      the genuineness of synesthesia, correlated significantly with performance in the
      partial report paradigm. We conclude that synesthesia does not generally enhance
      sensory memory performance, but that synesthetic experiences may enhance sensory
      memory performance when perceptual awareness of the target is high. Furthermore,
      the stability of synesthetic associations may be linked to sensory memory
      performance.

PMID- 30240717
TI  - Critical resolution: A superior measure of crowding.
AB  - Visual object recognition is essential for adaptive interactions with the
      environment. It is fundamentally limited by crowding, a breakdown of object
      recognition in clutter. The spatial extent over which crowding occurs is
      proportional to the eccentricity of the target object, but nevertheless varies
      substantially depending on various stimulus factors (e.g. viewing time,
      contrast). However, a lack of studies jointly manipulating such factors precludes
      predictions of crowding in more heterogeneous scenes, such as the majority of
      real life situations. To establish how such co-occurring variations affect
      crowding, we manipulated combinations of 1) flanker contrast and backward
      masking, 2) flanker contrast and presentation duration, and 3) flanker preview
      and pop-out while measuring participants' ability to correctly report the
      orientation of a target stimulus. In all three experiments, combining two
      manipulations consistently modulated the spatial extent of crowding in a way that
      could not be predicted from an additive combination. However, a simple
      transformation of the measurement scale completely abolished these interactions
      and all effects became additive. Precise quantitative predictions of the
      magnitude of crowding when combining multiple manipulations are thus possible
      when it is expressed in terms of what we label the 'critical resolution'.
      Critical resolution is proportional to the inverse of the smallest flanker free
      area surrounding the target object necessary for its unimpaired identification.
      It offers a more parsimonious description of crowding than the traditionally used
      critical spacing and may thus constitute a measure of fundamental importance for
      understanding object recognition.

PMID- 30240718
TI  - Reading sideways: Effects of egocentric and environmental orientation in a
      lexical decision task.
AB  - Many image-level factors affect reading speed and comprehension, including the in
      plane orientation of text. As words' angular deviation from upright increases, so
      do response times. Here we investigated whether these orientation effects in
      reading are based purely on an egocentric (retinal) reference frame, or whether
      there is also a contribution of the environmental reference frame. Participants
      completed a lexical decision task with six-letter, two-syllable words and
      nonwords presented at a wide range of angles, in increments of 22.5 degrees . A
      control group of participants (N = 66) completed the task while sitting upright,
      and an experimental group (N = 43) completed the task while lying sideways on
      their right side. The function relating the egocentric orientation of strings to
      response times was symmetric for upright observers, but skewed for observers who
      lay sideways, with an advantage for responding to environmentally upright text.
      Our results suggest that sideways readers may use an oblique reference frame
      (similar to the perceptual upright) for mentally rotating text. We discuss
      implications for designing optimal text orientations in head mounted displays.

PMID- 30240719
TI  - Modeling the effects of insecticides resistance on malaria vector control in
      endemic regions of Kenya.
AB  - We present a model to investigate the effects of vector resistance to control
      strategies. The model captures the development of resistance as well as loss of
      resistance in mosquitoes and how these affect the progress in malaria control.
      Important thresholds were calculated from mathematical analysis and numerical
      results presented. Mathematical results reveal the existence of the disease free
      and endemic equilibria whose existence and stability depends on the control
      reproduction number, Rc. The disease persist when the Rc>1 and dies out when
      Rc<1. Control strategies use and adherence needs to be highly efficacious to
      thwart the effects of insecticides resistance. Moreover, it is not enough to just
      eradicate resistant mosquitoes.

PMID- 30240720
TI  - Cell cycles during early steps of amphibian embryogenesis: A review.
AB  - The published data on cell cycles during the initial (pregastrular) period of
      embryonic development in representatives of the class Amphibia have been
      critically discussed. We have also used the literature data on ontogenetic
      diversity of these animals. The relatively small eggs of two principal model
      species for amphibian embryology, the Mexican axolotl and the African clawed
      frog, undergo the extensive series of rapid synchronous cleavage divisions, after
      which the midblastula transition (MBT) takes place: the rate of divisions slows
      down, the cell synchrony is lost, and the initiation of major transcriptional
      genomic activation occurs. However, many amphibians (including the basal species)
      are characterized by large, yolky, and slowly cleaving eggs with very short
      series of synchronous divisions. There is no reason to suggest the occurrence of
      the MBT in this case. The cleavage pattern in Ambystoma mexicanun (Caudata) and
      Xenopus laevis (Anura) represents a homoplasy and so the MBT, which is
      characteristic of the two model species, might have evolved convergently in these
      two amphibian orders as embryonic adaptations to lentic water habitats. This
      assumption about the convergent evolution explains some interspecific differences
      in the cytophysiological data on pregastrular embryos of the Mexican axolotl and
      the African clawed frog.

PMID- 30240721
TI  - The magnitude of respiratory sinus arrhythmia of a large mammal (the horse) is
      like that of humans.
AB  - Heart rate (FH) accelerates in inspiration and decelerates in expiration, a
      phenomenon known as Respiratory Sinus Arrhythmia (RSA). Although the presence of
      RSA has been documented in many species, how its magnitude compares among species
      is unknown. We asked whether the magnitude of RSA in a large mammal, the horse,
      differed from that of previously measured humans. From electrocardiogram and
      pneumography, the peaks and troughs of FH were identified breath-by-breath in
      four horses (Italian Saddlebred geldings) during resting wakefulness. RSA was
      computed as the peak-trough FH difference, in percent of mean FH. Horses had
      lower FH and respiratory frequency (FR) than humans, but similar FH/FR. RSA
      ranged between 6% and 15%, with an average of 9 +/- 2%, not statistically
      different from the mean value in humans (12 +/- 1%). Like in humans, in horses
      the FH/FR values below the mean had correspondingly lower RSA, while values above
      the mean had correspondingly higher RSA. If confirmed in other species, these
      results suggest that RSA is body size-independent. The correlation with FH/FR,
      rather than FH or FR, supports the view that RSA optimizes the coupling between
      pulmonary blood flow and ventilation.

PMID- 30240722
TI  - Re-evaluation of Current Prism Standards with Recommendations to Increase
      Accuracy in the Measurement of Strabismus.
AB  - PURPOSE: To critically evaluate the traditional standards for holding single
      prisms in measuring strabismus with the specific goal being to increase the
      overall accuracy of clinical measurements. DESIGN: Reliability and validity
      analysis METHODS: Using an analysis involving geometric optics, the effective
      prism power (EPP), measured in prism diopters (PD) was calculated for glass and
      acrylic prisms and was the main outcome measure. These results were also
      validated using optical bench measurements. No patients were involved. RESULTS:
      Plotting the calculated effective prism power as a function of rotational angle
      produced curves demonstrating that the frontal plane position lies along the
      flatter portions of the curves, while the Prentice position lies along the
      steeper portions of the curves. Calculated values of prism power for the standard
      clinical positions as well as the percentage errors from accepted standards were
      compared. Acrylic prisms can be held in the frontal plane position with
      acceptable amounts of error (<5%) for prisms up to 50 PD. Glass prisms are
      capable of producing significant errors for measurements much greater than 10 PD.
      CONCLUSIONS: The use of glass prisms as currently calibrated should be abandoned
      or at least limited to small measurements. Acrylic prisms produce acceptable
      errors if careful attention is given to their position.

PMID- 30240723
TI  - Diagnosis, clinical presentations and outcomes of Nocardia endophthalmitis.
AB  - PURPOSE: To describe the clinical presentations, diagnosis and management
      outcomes of Nocardia endophthalmitis DESIGN: Retrospective, interventional, multi
      centric case series. METHODS: The study was conducted in a multi-centric
      institutional practice setup including 25 eyes of 25 patients with culture-proven
      Nocardia endophthalmitis. AC fluid and/or vitreous and/or intraocular lens were
      submitted for microbiological evaluation is all cases. Patients with non-Nocardia
      etiology and those that were culture-negative were excluded. Case records were
      studied and data regarding demography, clinical presentations, interventions
      received and final visual and anatomic outcomes were noted. The main outcome
      measures were final visual outcomes and factors determining them. RESULTS: The
      mean age of the patients was 54.7+/-22.9 years. By the etiology of infection, 18
      (75%) eyes were post cataract surgery (operated elsewhere), 3 (12.5%) eyes were
      post-trauma and 3 (12.5%) eyes were endogenous. The final follow up in months was
      a mean of 14.25+/-30.35 months, median 2 months. The odds of a favorable outcome
      were 42.5 (95% C.I. 3.15 to 571.84 , p=0.0047) when the vision was more than hand
      motions at presentation, 9.42 (95% C.I. 0.92 to 95.89, p=0.05) in male gender, 21
      (95% C.I. 0.9 to 489.7, p=0.05) when presentation was within 48 hours and 2.5
      (95% C.I. 0.23 to 26.48, p=0.44) with primary vitrectomy instead of a biopsy. The
      in vitro susceptibility was poor for vancomycin and was best for amikacin.
      CONCLUSIONS: The visual outcome in Nocardia endophthalmitis is very guarded when
      presenting vision is poor. On diagnostic confirmation or high index of suspicion
      intravitreal amikacin is preferred.

PMID- 30240724
TI  - Repeatability and Reproducibility of Corneal Epithelial Thickness Mapping with
      Spectral Domain Optical Coherence Tomography in Normal and Diseased Cornea Eyes.
AB  - PURPOSE: To evaluate the performance of the epithelial thickness mapping (ETM) of
      the iVue spectral domain optical coherence tomography (SD-OCT) (Optovue Inc.,
      Fremont, CA) in normal and diseased cornea eyes. DESIGN: Reliability and validity
      analysis. METHODS: Sixty eyes of 60 subjects were recruited for the study that
      included normal subjects (n=12) and patients with corneal diseases (12 each with
      dry eye syndrome (DES), contact lens (CL) wear, post laser refractive surgery
      (LRS), and keratoconus (KCN)). Three repeated scans were acquired on 3 iVue SD
      OCTs with device-designated operators from consented subjects. Each subject was
      scanned on each device. Repeatability (based on random error of repeated scans)
      and reproducibility (including the random error and the instrument/operator
      variability) were assessed based on spatial zones derived from a 6 mm diameter
      corneal ETM centered on the pupil and compared between the groups. RESULTS: Fifty
      nine eyes qualified for final analysis. Seventy-one of 598 acquired scans (11.9%)
      were excluded due to scan quality concerns. The percentage of disqualified scans
      was similar across normal (10.7%) and diseased eyes (12.1%). Of 527 qualified
      scans, 40 (7.6%) scans required manual edits of the segmentation lines.
      Repeatability and reproducibility results were similar, indicating minimal
      device/operator variability for both groups. Repeatability and reproducibility
      were similar in all sub-groups of cornea patients, excluding the DES group, for
      which reproducibility was significantly lower (range 3.2-5.5% for DES patients
      and 1.1-2.9% for normal subjects). CONCLUSIONS: The iVue SD-OCT provides good
      corneal ETM repeatability and reproducibility in normal and diseased cornea eyes
      through all map zones.

PMID- 30240725
TI  - Choroideremia Gene Therapy Phase 2 Clinical Trial: 24-Month Results.
AB  - PURPOSE: To report the final results of a phase 2 high-dose gene therapy clinical
      trial in choroideremia. METHODS: DESIGN: Phase 2 clinical trial. PARTICIPANTS:
      Six men (age 32-72 years) with genetically-confirmed advanced choroideremia.
      Patients received subfoveal injection of AAV2-REP1 (1011 genome particles in 0.1
      mL) in the worse-sighted eye. OUTCOME MEASURES: Primary measure was best
      corrected visual acuity (BCVA) change from baseline in the treated eye compared
      to the untreated eye. Secondary endpoints included change from baseline in
      microperimetry, fundus autofluorescence, and spectral-domain optical coherence
      tomography (OCT). Safety evaluations included adverse events, viral shedding in
      body fluids, and vector antibody responses. RESULTS: Baseline mean ETDRS BCVA was
      65.3+/-8.8 (SD, range 56-77, 20/32-20/80) letters in the treated eyes and 77.0+/
      4.2 (69-81, 20/25-20/40) letters in the untreated eyes. At two years, one treated
      eye improved by 10 letters and another by 5 letters, while one untreated eye
      improved by 4 letters. All other eyes were within 2 letters of baseline. Baseline
      microperimetry sensitivities in the treated eyes were poor (1.2+/-2.1 (0,5.1) dB)
      and showed no significant change. No serious adverse event occurred. Two patients
      developed an atrophic retinal hole in a non-functioning macular area where
      baseline OCT showed pre-existing thinning. Intraoperative microscope-integrated
      OCT allowed proper subretinal injection with avoidance of excessive foveal
      stretching and macular hole formation. CONCLUSIONS: Sustained improvement or
      maintenance of BCVA is achievable in choroideremia with high-dose AAV2-REP1
      indicating BCVA is a viable primary outcome in advanced choroideremia.
      Choroideremia gene therapy delivered with intraoperative OCT has a good safety
      profile.

PMID- 30240726
TI  - Causes Of Visual Impairment And Blindness In The 2006 And 2014 Nine-Province
      Surveys In Rural China.
AB  - PURPOSE: Investigate the primary causes of visual impairment and blindness in
      rural China. DESIGN: Population-based, cross-sectional study. METHODS:
      Geographical cluster sampling was used in randomly selecting residents from a
      rural county/district within 9 provinces in the East Coast, Inland Middle and
      West regions of mainland China. Persons aged 50 years or older were enumerated
      through household visits and invited to examination sites for visual acuity
      testing and ocular examination. Causes of vision impairment and blindness in 2014
      were compared with data from an earlier 2006 survey. RESULTS: Mild visual
      impairment (20.4% prevalence) was caused by uncorrected refractive error in two
      thirds of cases and by cataract in nearly another one-fourth; moderate to severe
      visual impairment (10.3% prevalence), was caused by cataract in over one-half of
      cases and by uncorrected refractive error in another one-fifth; blindness (1.66%
      prevalence) was cause by cataract in approximately one-half of cases and in
      another one-fourth by retinal disease. Primary causes of visual impairment and
      blindness in cataract-operated eyes were uncorrected refractive error, posterior
      capsule opacity, and retinal disease. During 2006 to 2014, the proportion of
      visual impairment caused by uncorrected refractive error increased, but rates for
      unoperated cataract were reduced. CONCLUSIONS: Uncorrected refractive error and
      unoperated cataract are the two primary causes of mild, moderate and severe
      visual impairment in rural China, with unoperated cataract and retinal diseases
      primary causes for blindness. An effective public health strategy to increase
      service delivery for these causes would lead to substantial reduction in vision
      impairment and blindness.

PMID- 30240727
TI  - Magrabi ICO Cameroon Eye Institute, Yaounde, Cameroon: Ophthalmology Subspecialty
      Patient Care and Training Center in Central Africa.
AB  - PURPOSE: To report establishment of the Magrabi ICO Cameroon Eye Institute at
      Yaounde, Cameroon, as an ophthalmology subspecialty patient care and training
      center in Central Africa. DESIGN: Perspective METHODS: Assessment of unpublished
      and published material. RESULTS: To improve, preserve and restore eye health and
      vision in a region with world-high prevalence of functional vision impairment and
      blindness, the Africa Eye Foundation established the Magrabi ICO Cameroon Eye
      Institute as an ophthalmology subspecialty patient care center for all in need
      and a training center for ophthalmologists, ophthalmology subspecialists and
      allied personnel. In 2017, the year of Inauguration and the first year of
      operation, the Magrabi ICO Cameroon Eye Institute provided ophthalmology
      subspecialty care to more than 25,000 patients and surgery for pediatric and
      adult cataract, glaucoma, retinal disease, oculoplastic disorders and other
      vision threatening conditions. Outreach programs extended care to an additional
      2,500 individuals in rural communities and seven training courses were conducted
      for ophthalmologists and allied personnel. CONCLUSION: Through ophthalmology
      subspecialty patient care and the training of ophthalmologists and allied
      personnel, Magrabi ICO Cameroon Eye Institute is acting to enhance vision and the
      quality of life for individuals and families in all segments of society.

PMID- 30240728
TI  - EtCO2 measurement during pediatric cardiac arrest: Does the Emperor have no
      clothes?

PMID- 30240729
TI  - Mutagenic and genotoxic potential of pure Cylindrospermopsin by a battery of in
      vitro tests.
AB  - Cylindrospermopsin (CYN) is a cyanobacterial toxin with an increasing world-wide
      occurrence. The main route of human exposure is through the ingestion of
      contaminated food and water. The European Food Safety Authority has identified
      the need to further characterize the toxicological profile of cyanotoxins and in
      this regard the genotoxicity is a key toxicological effect. The data available in
      the scientific literature show contradictory results. Thus, the aim of this study
      was to investigate the mutagenic and genotoxic effects of pure CYN using a
      battery of different in vitro assays including: the bacterial reverse-mutation
      assay in Salmonella typhimurium (Ames test) (0-10 MUg/mL), the mammalian cell
      micronucleus (MN) test (0-1.35 MUg/mL and 0-2 MUg/mL in absence or presence of S9
      fraction, respectively) and the mouse lymphoma thymidine-kinase assay (MLA)(0
      0.675 MUg/mL) on L5178YTk +/- cells, and the standard and enzyme-modified comet
      assays (0-2.5 MUg/mL) on Caco-2 cells. Positive results were obtained only when
      the metabolic fraction S9 was employed in the MN test, suggesting pro-genotoxic
      properties of CYN. Also, DNA damage was not mediated by oxidative stress as CYN
      did not induced changes in the modified comet assay. These data could contribute
      to a better risk assessment of this cyanotoxin.

PMID- 30240730
TI  - RIFM fragrance ingredient safety assessment, benzothiazole, CAS Registry Number
      95-16-9.

PMID- 30240731
TI  - Xanthohumol inhibits cell proliferation and induces apoptosis in human thyroid
      cells.
AB  - The cell growth inhibitory potential of xanthohumol (XN), a natural
      prenylflavonoid present in hops and beer, on human papillary thyroid cancer cells
      is reported. We demonstrate that XN decreases the proliferation of TPC-1 cancer
      cells in a dose and time dependent manners. At low concentration (10 MUM) XN was
      shown to significantly inhibit carcinogenesis by a mechanism that stops or slows
      down cell division, preserving the viability of the cells. At higher
      concentration (100 MUM) a decrease of cell viability was observed by induction of
      apoptosis. As evidenced, XN induced DNA fragmentation in TPC-1 cells and promoted
      cell cycle arrest, which decreased the percentage of cells in G1 phase and
      increased in S phase after 72 h of treatment. Furthermore, XN exposure triggered
      an increase in caspase-3 and caspase-7 activity, supporting its role in the
      activation of apoptosis. Cell-free studies demonstrated that high concentrations
      of XN are responsible for an increase of free radicals generated in a Fenton
      system which may mediate apoptosis through a pro-oxidant pathway. Altogether, our
      data show that XN induces the apoptosis of TPC-1 cancer cells in a concentration
      dependent manner, suggesting XN to be a promising candidate for thyroid cancer
      therapy.

PMID- 30240732
TI  - RIFM fragrance ingredient safety assessment, p-mentha-1,8-dien-7-ol, CAS Registry
      Number 536-59-4.

PMID- 30240733
TI  - A Small Chaperone Improves Folding and Routing of Rhodopsin Mutants Linked to
      Inherited Blindness.
AB  - The autosomal dominant form of retinitis pigmentosa (adRP) is a blindness-causing
      conformational disease largely linked to mutations of rhodopsin. Molecular
      simulations coupled to the graph-based protein structure network (PSN) analysis
      and in vitro experiments were conducted to determine the effects of 33 adRP
      rhodopsin mutations on the structure and routing of the opsin protein. The
      integration of atomic and subcellular levels of analysis was accomplished by the
      linear correlation between indices of mutational impairment in structure network
      and in routing. The graph-based index of structural perturbation served also to
      divide the mutants in four clusters, consistent with their differences in
      subcellular localization and responses to 9-cis retinal. The stability core of
      opsin inferred from PSN analysis was targeted by virtual screening of over
      300,000 anionic compounds leading to the discovery of a reversible orthosteric
      inhibitor of retinal binding more effective than retinal in improving routing of
      three adRP mutants.

PMID- 30240734
TI  - Chromatin Remodeling BAF155 Subunit Regulates the Genesis of Basal Progenitors in
      Developing Cortex.
AB  - The abundance of basal progenitors (BPs), basal radial glia progenitors (bRGs)
      and basal intermediate progenitors (bIPs), in primate brain has been correlated
      to the high degree of cortical folding. Here we examined the role of BAF155, a
      subunit of the chromatin remodeling BAF complex, in generation of cortical
      progenitor heterogeneity. The conditional deletion of BAF155 led to diminished
      bIP pool and increased number of bRGs, due to delamination of apical RGs. We
      found that BAF155 is required for normal activity of neurogenic transcription
      factor PAX6, thus controlling the expression of genes that are involved in bIP
      specification, cell-cell interaction, and establishment of adherens junction. In
      a PAX6-dependent manner, BAF155 regulates the expression of the CDC42 effector
      protein CEP4, thereby controlling progenitor delamination. Furthermore, BAF155
      dependent chromatin remodeling seems to exert a specific role in the genesis of
      BPs through the regulation of human RG-specific genes (such as Foxn4) that
      possibly acquired evolutionary significance.

PMID- 30240736
TI  - Identifying MnVII-oxo Species during Electrochemical Water Oxidation by Manganese
      Oxide.
AB  - Identifying surface active intermediate species is essential to reveal the
      catalytic mechanism of water oxidation by metal-oxides-based catalysts and to
      develop more efficient catalysts for oxygen-oxygen bond formation. Here we
      report, through electrochemical methods and ex situ infrared spectroscopy, the
      identification of a MnVII = O intermediate during catalytic water oxidation by a
      c-disordered delta-MnOx with an onset-potential-dependent reduction peak at 0.93
      V and an infrared peak at 912 cm-1. This intermediate is proved to be highly
      reactive and much more oxidative than permanganate ion. Therefore, we propose a
      new catalytic mechanism for water oxidation catalyzed by Mn oxides, with
      involvement of the MnVII = O intermediate in a resting state and the MnIV-O-MnVII
      = O as a real active species for oxygen-oxygen bond formation.

PMID- 30240735
TI  - Biomechanical Control of Lysosomal Secretion Via the VAMP7 Hub: A Tug-of-War
      between VARP and LRRK1.
AB  - The rigidity of the cell environment can vary tremendously between tissues and in
      pathological conditions. How this property may affect intracellular membrane
      dynamics is still largely unknown. Here, using atomic force microscopy, we show
      that cells deficient in the secretory lysosome v-SNARE VAMP7 are impaired in
      adaptation to substrate rigidity. Conversely, VAMP7-mediated secretion is
      stimulated by more rigid substrate and this regulation depends on the Longin
      domain of VAMP7. We further find that the Longin domain binds the kinase and
      retrograde trafficking adaptor LRRK1 and that LRRK1 negatively regulates VAMP7
      mediated exocytosis. Conversely, VARP, a VAMP7- and kinesin 1-interacting
      protein, further controls the availability for secretion of peripheral VAMP7
      vesicles and response of cells to mechanical constraints. LRRK1 and VARP interact
      with VAMP7 in a competitive manner. We propose a mechanism whereby biomechanical
      constraints regulate VAMP7-dependent lysosomal secretion via LRRK1 and VARP tug
      of-war control of the peripheral pool of secretory lysosomes.

PMID- 30240737
TI  - Porphyrin Dyes for Nonlinear Optical Imaging of Live Cells.
AB  - Second harmonic generation (SHG)-based probes are useful for nonlinear optical
      imaging of biological structures, such as the plasma membrane. Several
      amphiphilic porphyrin-based dyes with high SHG coefficients have been synthesized
      with different hydrophilic head groups, and their cellular targeting has been
      studied. The probes with cationic head groups localize better at the plasma
      membrane than the neutral probes with zwitterionic or non-charged ethylene glycol
      based head groups. Porphyrin dyes with only dications as hydrophilic head groups
      localize inside HEK293T cells to give SHG, whereas tricationic dyes localize
      robustly at the plasma membrane of cells, including neurons, in vitro and ex
      vivo. The copper(II) complex of the tricationic dye with negligible fluorescence
      quantum yield works as an SHG-only dye. The free-base tricationic dye has been
      demonstrated for two-photon fluorescence and SHG-based multimodal imaging. This
      study demonstrates the importance of a balance between the hydrophobicity and
      hydrophilicity of amphiphilic dyes for effective plasma membrane localization.

PMID- 30240738
TI  - Comparative Transcriptomics in Two Extreme Neopterans Reveals General Trends in
      the Evolution of Modern Insects.
AB  - The success of neopteran insects, with 1 million species described, is associated
      with developmental innovations such as holometaboly and the evolution from short
      to long germband embryogenesis. To unveil the mechanisms underlining these
      innovations, we compared gene expression during the ontogeny of two extreme
      neopterans, the cockroach Blattella germanica (polyneopteran, hemimetabolan, and
      short germband species) and the fly Drosophila melanogaster (endopterygote,
      holometabolan, and long germband species). Results revealed that genes associated
      with metamorphosis are predominantly expressed in late nymphal stages in B.
      germanica and in the early-mid embryo in D. melanogaster. In B. germanica the
      maternal to zygotic transition (MZT) concentrates early in embryogenesis, when
      juvenile hormone factors are significantly expressed. In D. melanogaster, the MZT
      extends throughout embryogenesis, during which time juvenile hormone factors
      appear to be unimportant. These differences possibly reflect broad trends in the
      evolution of development within neopterans, related to the germband type and the
      metamorphosis mode.

PMID- 30240739
TI  - Constriction Rate Modulation Can Drive Cell Size Control and Homeostasis in C.
      crescentus.
AB  - Rod-shaped bacteria typically grow first via sporadic and dispersed elongation
      along their lateral walls and then via a combination of zonal elongation and
      constriction at the division site to form the poles of daughter cells. Although
      constriction comprises up to half of the cell cycle, its impact on cell size
      control and homeostasis has rarely been considered. To reveal the roles of cell
      elongation and constriction in bacterial size regulation during cell division, we
      captured the shape dynamics of Caulobacter crescentus with time-lapse structured
      illumination microscopy and used molecular markers as cell-cycle landmarks. We
      perturbed the constriction rate using a hyperconstriction mutant or fosfomycin
      ([(2R,3S)-3-methyloxiran-2-yl]phosphonic acid) inhibition. We report that the
      constriction rate contributes to both size control and homeostasis, by
      determining elongation during constriction and by compensating for variation in
      pre-constriction elongation on a single-cell basis.

PMID- 30240740
TI  - Growth Cone Phosphoproteomics Reveals that GAP-43 Phosphorylated by JNK Is a
      Marker of Axon Growth and Regeneration.
AB  - Neuronal growth cones are essential for nerve growth and regeneration, as well as
      for the formation and rearrangement of the neural network. To elucidate
      phosphorylation-dependent signaling pathways and establish useful molecular
      markers for axon growth and regeneration, we performed a phosphoproteomics study
      of mammalian growth cones, which identified >30,000 phosphopeptides of ~1,200
      proteins. The phosphorylation sites were highly proline directed and primarily
      MAPK dependent, owing to the activation of JNK, suggesting that proteins that
      undergo proline-directed phosphorylation mediate nerve growth in the mammalian
      brain. Bioinformatics analysis revealed that phosphoproteins were enriched in
      microtubules and the cortical cytoskeleton. The most frequently phosphorylated
      site was S96 of GAP-43 (growth-associated protein 43-kDa), a vertebrate-specific
      protein involved in axon growth. This previously uncharacterized phosphorylation
      site was JNK dependent. S96 phosphorylation was specifically detected in growing
      and regenerating axons as the most frequent target of JNK signaling; thus it
      represents a promising new molecular marker for mammalian axonal growth and
      regeneration.

PMID- 30240742
TI  - RNAs as Proximity-Labeling Media for Identifying Nuclear Speckle Positions
      Relative to the Genome.
AB  - It remains challenging to identify all parts of the nuclear genome that are in
      proximity to nuclear speckles, due to physical separation between the nuclear
      speckle cores and chromatin. We hypothesized that noncoding RNAs including small
      nuclear RNA (snRNAs) and Malat1, which accumulate at the periphery of nuclear
      speckles (nsaRNA [nuclear speckle-associated RNA]), may extend to sufficient
      proximity to the genome. Leveraging a transcriptome-genome interaction assay
      (mapping of RNA-genome interactions [MARGI]), we identified clusters of nsaRNA
      interacting genomic sequences (nsaPeaks). Posttranscriptional pre-mRNAs, which
      also accumulate to nuclear speckles, exhibited proximity to nsaPeaks but rarely
      to other genomic regions. Our combined DNA fluorescence in situ hybridization and
      immunofluorescence analysis in 182 single cells revealed a 3-fold increase in
      odds for nuclear speckles to localize near an nsaPeak than its neighboring
      genomic sequence. These data suggest a model that nsaRNAs are located in
      sufficient proximity to the nuclear genome and leave identifiable genomic
      footprints, thus revealing the parts of genome proximal to nuclear speckles.

PMID- 30240743
TI  - Piezoelectrically Enhanced Photocatalysis with BiFeO3 Nanostructures for
      Efficient Water Remediation.
AB  - Designing new catalysts that can efficiently utilize multiple energy sources can
      contribute to solving the current challenges of environmental remediation and
      increasing energy demands. In this work, we fabricated single-crystalline BiFeO3
      (BFO) nanosheets and nanowires that can successfully harness visible light and
      mechanical vibrations and utilize them for degradation of organic pollutants.
      Under visible light both BFO nanostructures displayed a relatively slow reaction
      rate. However, under piezocatalysis both nanosheets and nanowires exhibited
      higher reaction rates in comparison with photocatalytic degradation. When both
      solar light and mechanical vibrations were used simultaneously, the reaction
      rates were elevated even further, with the BFO nanowires degrading 97% of RhB dye
      within 1 hr (k-value 0.058 min-1). The enhanced degradation under mechanical
      vibrations can be attributed to the promotion of charge separation caused by the
      internal piezoelectric field of BFO. BFO nanowires also exhibited good
      reusability and versatility toward degrading four different organic pollutants.

PMID- 30240741
TI  - Human Organ-Specific Endothelial Cell Heterogeneity.
AB  - The endothelium first forms in the blood islands in the extra-embryonic yolk sac
      and then throughout the embryo to establish circulatory networks that further
      acquire organ-specific properties during development to support diverse organ
      functions. Here, we investigated the properties of endothelial cells (ECs),
      isolated from four human major organs-the heart, lung, liver, and kidneys-in
      individual fetal tissues at three months' gestation, at gene expression, and at
      cellular function levels. We showed that organ-specific ECs have distinct
      expression patterns of gene clusters, which support their specific organ
      development and functions. These ECs displayed distinct barrier properties,
      angiogenic potential, and metabolic rate and support specific organ functions.
      Our findings showed the link between human EC heterogeneity and organ development
      and can be exploited therapeutically to contribute in organ regeneration, disease
      modeling, as well as guiding differentiation of tissue-specific ECs from human
      pluripotent stem cells.

PMID- 30240745
TI  - Mutant and Wild-Type Tumor Suppressor p53 Induces p300 Autoacetylation.
AB  - The transcriptional co-activator p300 is essential for p53 transactivation,
      although its precise role remains unclear. We report that p53 activates the
      acetyltransferase activity of p300 through the enhancement of p300
      autoacetylation. Autoacetylated p300 accumulates near the transcription start
      sites accompanied by a similar enrichment of activating histone marks near those
      sites. Abrogation of p53-p300 interaction by a site-directed peptide inhibitor
      abolished p300-mediated histone acetylation, suggesting a crucial role played by
      the activation in p53-mediated gene regulation. Gain-of-function mutant p53,
      known to impart aggressive proliferative properties in tumor cells, also
      activates p300 autoacetylation. The same peptide abolished many of the gain-of
      function properties of mutant p53 as well. Reversal of gain-of-function
      properties of mutant p53 suggests that molecules targeting the p53-p300 interface
      may be good candidates for anti-tumor drugs.

PMID- 30240744
TI  - Microbial Quantity Impacts Drosophila Nutrition, Development, and Lifespan.
AB  - In Drosophila, microbial association can promote development or extend life. We
      tested the impact of microbial association during malnutrition and show that
      microbial quantity is a predictor of fly longevity. Although all tested microbes,
      when abundantly provided, can rescue lifespan on low-protein diet, the effect of
      a single inoculation seems linked to the ability of that microbial strain to
      thrive under experimental conditions. Microbes, dead or alive, phenocopy dietary
      protein, and the calculated dependence on microbial protein content is similar to
      the protein requirements determined from fly feeding studies, suggesting that
      microbes enhance host protein nutrition by serving as protein-rich food. Microbes
      that enhance larval growth are also associated with the ability to better thrive
      on fly culture medium. Our results suggest an unanticipated range of microbial
      species that promote fly development and longevity and highlight microbial
      quantity as an important determinant of effects on physiology and lifespan during
      undernutrition.

PMID- 30240746
TI  - Human Listeners Can Accurately Judge Strength and Height Relative to Self from
      Aggressive Roars and Speech.
AB  - Although animal vocalizations and human speech are known to communicate physical
      formidability, no previous study has examined whether human listeners can assess
      the strength or body size of vocalizers relative to their own, either from speech
      or from nonverbal vocalizations. Here, although men tended to underestimate
      women's formidability, and women to overestimate men's, listeners judged relative
      strength and height from aggressive roars and aggressive speech accurately. For
      example, when judging roars, male listeners accurately identified vocalizers who
      were substantially stronger than themselves in 88% of trials, and never as
      weaker. For male vocalizers only, roars functioned to exaggerate the expression
      of threat compared to aggressive speech, as men were rated as relatively stronger
      when producing roars. These results indicate that, like other mammals, the
      acoustic structure of human aggressive vocal signals (and in particular roars)
      may have been selected to communicate functional information relevant to
      listeners' survival.

PMID- 30240747
TI  - Controlling Cell Fate Specification System by Key Genes Determined from Network
      Structure.
AB  - Network structures describing regulation between biomolecules have been
      determined in many biological systems. Dynamics of molecular activities based on
      such networks are considered to be the origin of many biological functions.
      Recently, it has been proved mathematically that key nodes for controlling
      dynamics in networks are identified from network structure alone. Here, we
      applied this theory to a gene regulatory network for the cell fate specification
      of seven tissues in the ascidian embryo and found that this network, which
      consisted of 92 factors, had five key molecules. By controlling the activities of
      these key molecules, the specific gene expression of six of seven tissues
      observed in the embryo was successfully reproduced. Since this method is
      applicable to all nonlinear dynamic systems, we propose this method as a tool for
      controlling gene regulatory networks and reprogramming cell fates.

PMID- 30240748
TI  - Digitalized Human Organoid for Wireless Phenotyping.
AB  - Radio frequency identification (RFID) is a cost-effective and durable method to
      trace and track individual objects in multiple contexts by wirelessly providing
      digital signals; RFID is thus widely used in many fields. Here, we implement this
      concept to biological tissues by producing a compact RFID chip-incorporated
      organoid (RiO). The 0.4 mm RFID chips are reproducibly integrated inside the self
      assembling organoids from 10 different induced pluripotent stem cell (iPSC) lines
      from healthy and diseased donors. We use the digitalized RiO to conduct a
      phenotypic screen on a pool of RiO, followed by detection of each specific donor
      in situ. Our proof-of-principle experiments demonstrated that a severely
      steatotic phenotype could be identified by RFID chip reading and was specific to
      a genetic disorder of steatohepatitis. Given evolving advancements surrounding
      RFID technology, the digitalization principle outlined here will expand organoid
      medicine potential toward drug development, precision medicine, and transplant
      applications.

PMID- 30240749
TI  - Printable Metal-Polymer Conductors for Highly Stretchable Bio-Devices.
AB  - Stretchable, biocompatible devices can bridge electronics and biology. However,
      most stretchable conductors for such devices are toxic, costly, and regularly
      break/degrade after several large deformations. Here we show printable, highly
      stretchable, and biocompatible metal-polymer conductors by casting and peeling
      off polymers from patterned liquid metal particles, forming surface-embedded
      metal in polymeric hosts. Our printable conductors present good stretchability
      (2,316 S/cm at a strain of 500%) and repeatability (DeltaR/R <3% after 10,000
      cycles), which can satisfy most electrical applications in extreme deformations.
      This strategy not only overcomes large surface tension of liquid metal but also
      avoids the undesirable sintering of its particles by stress in deformations, such
      that stretchable conductors can form on various substrates with high resolution
      (15 MUm), high throughput (~2,000 samples/hour), and low cost (one-quarter price
      of silver). We use these conductors for stretchable circuits, motion sensors,
      wearable glove keyboards, and electroporation of live cells.

PMID- 30240750
TI  - Marked Global DNA Hypomethylation Is Associated with Constitutive PD-L1
      Expression in Melanoma.
AB  - Constitutive expression of the immune checkpoint, PD-L1, inhibits anti-tumor
      immune responses in cancer, although the factors involved in PD-L1 regulation are
      poorly understood. Here we show that loss of global DNA methylation, particularly
      in intergenic regions and repeat elements, is associated with constitutive (PD
      L1CON), versus inducible (PD-L1IND), PD-L1 expression in melanoma cell lines. We
      further show this is accompanied by transcriptomic up-regulation. De novo
      epigenetic regulators (e.g., DNMT3A) are strongly correlated with PD-L1
      expression and methylome status. Accordingly, decitabine-mediated inhibition of
      global methylation in melanoma cells leads to increased PD-L1 expression.
      Moreover, viral mimicry and immune response genes are highly expressed in
      lymphocyte-negative plus PD-L1-positive melanomas, versus PD-L1-negative
      melanomas in The Cancer Genome Atlas (TCGA). In summary, using integrated genomic
      analysis we identified that global DNA methylation influences PD-L1 expression in
      melanoma, and hence melanoma's ability to evade anti-tumor immune responses.
      These results have implications for combining epigenetic therapy with
      immunotherapy.

PMID- 30240751
TI  - MOF-derived Cobalt Sulfide Grown on 3D Graphene Foam as an Efficient Sulfur Host
      for Long-Life Lithium-Sulfur Batteries.
AB  - Lithium-sulfur (Li-S) batteries are an appealing candidate for advanced energy
      storage systems because of their high theoretical energy density and low cost.
      However, rapid capacity decay and short cycle life, mainly resulting from
      polysulfide dissolution, remains a great challenge for practical applications.
      Herein, we present a metal-organic framework (MOF)-derived Co9S8 array anchored
      onto a chemical vapor deposition (CVD)-grown three-dimensional graphene foam
      (Co9S8-3DGF) as an efficient sulfur host for long-life Li-S batteries with good
      performance. Without polymeric binders, conductive additives, or metallic current
      collectors, the free-standing Co9S8-3DGF/S cathode achieves a high areal capacity
      of 10.9 mA hr cm-2 even at a very high sulfur loading (10.4 mg cm-2) and sulfur
      content (86.9 wt%). These results are attributed to the unique hierarchical
      nanoarchitecture of Co9S8-3DGF/S. This work is expected to open up a promising
      direction for the practical viability of high-energy Li-S batteries.

PMID- 30240753
TI  - Application of Algebraic Topology to Homologous Recombination of DNA.
AB  - Brouwer's fixed point theorem, a fundamental theorem in algebraic topology proved
      more than a hundred years ago, states that given any continuous map from a
      closed, simply connected set into itself, there is a point that is mapped unto
      itself. Here we point out the connection between a one-dimensional application of
      Brouwer's fixed point theorem and a mechanism proposed to explain how extension
      of single-stranded DNA substrates by recombinases of the RecA superfamily
      facilitates significantly the search for homologous sequences on long
      chromosomes.

PMID- 30240752
TI  - Aryl Hydrocarbon Receptor Promotes Liver Polyploidization and Inhibits PI3K, ERK,
      and Wnt/beta-Catenin Signaling.
AB  - Aryl hydrocarbon receptor (AhR) deficiency alters tissue homeostasis. However,
      how AhR regulates organ maturation and differentiation remains mostly unknown.
      Liver differentiation entails a polyploidization process fundamental for cell
      growth, metabolism, and stress responses. Here, we report that AhR regulates
      polyploidization during the preweaning-to-adult mouse liver maturation.
      Preweaning AhR-null (AhR-/-) livers had smaller hepatocytes, hypercellularity,
      altered cell cycle regulation, and enhanced proliferation. Those phenotypes
      persisted in adult AhR-/- mice and correlated with compromised polyploidy,
      predominance of diploid hepatocytes, and enlarged centrosomes.
      Phosphatidylinositol-3-phosphate kinase (PI3K), extracellular signal-regulated
      kinase (ERK), and Wnt/beta-catenin signaling remained upregulated from preweaning
      to adult AhR-null liver, likely increasing mammalian target of rapamycin (mTOR)
      activation. Metabolomics revealed the deregulation of mitochondrial oxidative
      phosphorylation intermediates succinate and fumarate in AhR-/- liver.
      Consistently, PI3K, ERK, and Wnt/beta-catenin inhibition partially rescued
      polyploidy in AhR-/- mice. Thus, AhR may integrate survival, proliferation, and
      metabolism for liver polyploidization. Since tumor cells tend to be polyploid,
      AhR modulation could have therapeutic value in the liver.

PMID- 30240754
TI  - Generation of Drosophila sisRNAs by Independent Transcription from Cognate
      Introns.
AB  - Although stable intronic sequence RNAs (sisRNAs) are conserved in plants and
      animals, their functional significance is still unclear. We identify a pool of
      polyadenylated maternally deposited sisRNAs in Drosophila melanogaster. These
      sisRNAs can be generated by independent transcription from the cognate introns.
      The ovary-specific poly(A) polymerase Wispy mediates the polyadenylation of
      maternal sisRNAs and confers their stability as maternal transcripts. A
      developmentally regulated sisRNA sisR-3 represses the expression of a long
      noncoding RNA CR44148 and is required during development. Our results expand the
      pool of sisRNAs and suggest that sisRNAs perform regulatory functions during
      development in Drosophila.

PMID- 30240755
TI  - High Precision of Spike Timing across Olfactory Receptor Neurons Allows Rapid
      Odor Coding in Drosophila.
AB  - In recent years, it has become evident that olfaction is a fast sense, and
      millisecond short differences in stimulus onsets are used by animals to analyze
      their olfactory environment. In contrast, olfactory receptor neurons are thought
      to be relatively slow and temporally imprecise. These observations have led to a
      conundrum: how, then, can an animal resolve fast stimulus dynamics and smell with
      high temporal acuity? Using parallel recordings from olfactory receptor neurons
      in Drosophila, we found hitherto unknown fast and temporally precise odorant
      evoked spike responses, with first spike latencies (relative to odorant arrival)
      down to 3 ms and with a SD below 1 ms. These data provide new upper bounds for
      the speed of olfactory processing and suggest that the insect olfactory system
      could use the precise spike timing for olfactory coding and computation, which
      can explain insects' rapid processing of temporal stimuli when encountering
      turbulent odor plumes.

PMID- 30240756
TI  - A Combined In Vitro/In Silico Approach to Identifying Off-Target Receptor
      Toxicity.
AB  - Many xenobiotics can bind to off-target receptors and cause toxicity via the
      dysregulation of downstream transcription factors. Identification of subsequent
      off-target toxicity in these chemicals has often required extensive chemical
      testing in animal models. An alternative, integrated in vitro/in silico approach
      for predicting toxic off-target functional responses is presented to refine in
      vitro receptor identification and reduce the burden on in vivo testing. As part
      of the methodology, mathematical modeling is used to mechanistically describe
      processes that regulate transcriptional activity following receptor-ligand
      binding informed by transcription factor signaling assays. Critical reactions in
      the signaling cascade are identified to highlight potential perturbation points
      in the biochemical network that can guide and optimize additional in vitro
      testing. A physiologically based pharmacokinetic model provides information on
      the timing and localization of different levels of receptor activation informing
      whole-body toxic potential resulting from off-target binding.

PMID- 30240758
TI  - Whole-tumor histogram analysis of non-Gaussian distribution DWI parameters to
      differentiation of pancreatic neuroendocrine tumors from pancreatic ductal
      adenocarcinomas.
AB  - PURPOSE: To evaluate the utility of volumetric histogram analysis of
      monoexponential and non-Gaussian distribution DWI models for discriminating
      pancreatic ductal adenocarcinoma (PDAC) and neuroendocrine tumor (pNET).
      MATERIALS AND METHODS: A total of 340 patients were retrospectively reviewed.
      Finally, 62 patients with histopathological confirmed PDAC (n = 42) and pNET (n =
      20) were enrolled in the study. All the patients accepted magnetic resonance
      imaging (MRI) at 3 T (including multi-b value DWI, 0-1000 s/mm2). Isotropic
      apparent diffusion coefficient (ADC), true molecular diffusion (Dt), perfusion
      related diffusion (Dp), perfusion fraction (f), distributed diffusion coefficient
      (DDC) and alpha (alpha) were obtained from different DWI models. Then, mean
      value, median value, 10th and 90th percentiles were obtained from histogram
      analysis of each DWI parameter. RESULTS: Histogram metrics derived from ADC, Dp,
      f and DDC were significantly lower in PDAC than pNET group (P < 0.05). In
      contrast, histogram metrics derived from alpha were observed significantly higher
      in the PDAC than pNET group (P < 0.05). No significant difference was found in Dt
      (P >= 0.05) between PDAC and pNET patients. Among all parameters, f-median had
      the highest diagnostic performance (AUC 0.91, cutoff value 0.188, sensitivity
      97.62%, specificity 80%). CONCLUSIONS: f-Median derived from IVIM DWI model may
      be potentially more valuable parameter than ADC, Dp, DDC and alpha for
      discriminating PDAC and pNET. Histogram analysis based on the entire tumor was an
      emerging and valuable tool.

PMID- 30240760
TI  - Invited Commentary.

PMID- 30240759
TI  - Compressive sensing image recovery using dictionary learning and shape-adaptive
      DCT thresholding.
AB  - Compressed sensing (CS) has shown to be a successful technique for image
      recovery. Designing an effective regularization term reflecting the image sparse
      prior information plays a critical role in this field. Dictionary learning (DL)
      strategy alleviates the drawback of fixed bases. But the structure information of
      the image is easy to be blurred in complex regions due to the absence of sparsity
      in dictionary learning. This paper proposes a novel joint dictionary learning and
      Shape-Adaptive DCT (SADCT) thresholding method. We first propose to exploit
      sparsity of image in shape-adaptive regions, which is beneficial to medical
      images of complex textures. In this framework, the local sparsity depicts the
      smoothness redundancies exploited by dictionary learning. Moreover, the sparsity
      is enhanced especially in detail areas by the newly introduced SADCT
      thresholding. The attenuated SADCT coefficients are used to reconstruct a local
      estimation of the signal within the adaptive-shape support. Image is represented
      sparser in SADCT transform domain and the details of the image information can be
      kept with a much larger probability. Based on split Bregman iterations, an
      efficient alternating minimization algorithm is developed to solve the proposed
      CS medical image recovery problem. The results of various experiments on MR
      images consistently demonstrate that the proposed algorithm efficiently recovers
      MR images and shows advantages over the current leading CS reconstruction
      approaches.

PMID- 30240757
TI  - Ras Post-transcriptionally Enhances a Pre-malignantly Primed EMT to Promote
      Invasion.
AB  - Epithelial-to-mesenchymal transition (EMT) is integral to cancer progression,
      with considerable evidence that EMT has multiple intermediary stages.
      Understanding the mechanisms of this stepwise activation is of great interest. We
      recreated a genetically defined model in which primary cells were immortalized,
      resulting in migratory capacity, and subsequently H-Ras-transformed, causing
      malignancy and invasion. To determine the mechanisms coordinating stepwise
      malignancy, we quantified the changes in messenger RNA (mRNA) and protein
      abundance. During immortalization, we found dramatic changes in mRNA, consistent
      with EMT, which correlated with protein abundance. Many of these same proteins
      also changed following Ras transformation, suggesting that pre-malignant cells
      were primed for malignant conversion. Unexpectedly, changes in protein abundance
      did not correlate with changes in mRNA following transformation. Importantly,
      proteins involved in cellular adhesion and cytoskeletal structure decreased
      during immortalization and decreased further following Ras transformation,
      whereas their encoding mRNAs only changed during the immortalization step. Thus,
      Ras induced EMT-associated invasion via post-transcriptional mechanisms in primed
      pre-malignant cells.

PMID- 30240761
TI  - Invited Commentary.

PMID- 30240762
TI  - Short-Term Outcomes of Tracheal Resection in The Society of Thoracic Surgeons
      Database.
AB  - BACKGROUND: Tracheal surgery is uncommon, and most of the published literature
      consists of single-center series over large periods. Our goal was to perform a
      national, contemporary analysis to identify predictors of major morbidity and
      mortality based on indication and surgical approach. METHODS: The Society of
      Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) was queried for
      all patients undergoing tracheal resection between 2002 and 2016. We identified
      1,617 cases and compared outcomes by indication and approach. We created a
      multivariable model for a combined end point of mortality or major morbidity. The
      relationship between volume and outcome was analyzed. RESULTS: The cervical
      approach was used 81% of the time, and benign disease was the indication in 75%
      of cases. Overall 30-day mortality was 1%, and no significant difference was
      found between the cervical and thoracic approach (1.1% versus 1.6%, p = 0.57) or
      between benign and malignant indications (1.1% versus 1.5%, p = 0.61).
      Independent factors associated with morbidity or mortality included thoracic
      approach, diabetes, and functional status. Centers were divided into those
      averaging fewer than four resections per year and those performing at least four
      per year. The low volume (<4) group had a combined morbidity and mortality of
      27%, significantly higher than 17% observed among centers with more than four per
      year (p < 0.0001). CONCLUSIONS: STS GTSD participants perform tracheal resection
      for benign and malignant disease with low early morbidity and mortality. Higher
      operative volume is associated with improved outcome. Longer follow-up is needed
      to confirm airway stability and rate of reoperation.

PMID- 30240763
TI  - A Single-Center Experience of 900 Interhospital Transports on Extracorporeal
      Membrane Oxygenation.
AB  - BACKGROUND: The dawning of the extracorporeal membrane oxygenation (ECMO)-2 era,
      with the potential of decentralizing ECMO treatment, has stressed the need for
      research into the safety of ECMO transportations. The aim of this study was to
      (1) provide a comprehensive summary of transport arrangements and complications
      at a high-volume ECMO center, (2) determine predictors of severe complications
      occurring during transport, and (3) determine transport-related predictors of
      mortality. METHODS: This was a retrospective population-based observational
      cohort study of all interhospital ECMO transports performed by the Karolinska
      University Hospital between 1996 and 2017. Medical records, clinical notes, and
      original transport protocols were collected and reviewed. RESULTS: A total of 908
      ECMO transports were performed. Neonatal and pediatric patients were more likely
      to be subjected to international transport, air transport, and longer transport
      distances and transport times. A severe complication occurred in 20% of
      transports and was significantly associated with venoarterial ECMO (p = 0.04) and
      fixed-wing transport (p = 0.01). Severe transport complications were not
      associated with increased mortality. Two patients passed away during
      transportation. CONCLUSIONS: Severe complications during ECMO transportation
      recurrently occurred but did not affect mortality. We conclude that interhospital
      ECMO transportation is safe, when conducted by an experienced center, and
      patients should be transported for treatment at a high-volume ECMO center in
      accordance with the hub-and-spoke model whenever feasible.

PMID- 30240764
TI  - Segmentectomy Is Equivalent to Lobectomy in Hypermetabolic Clinical Stage IA Lung
      Adenocarcinomas.
AB  - BACKGROUND: Recent studies have suggested that lobectomy and segmentectomy hold
      equivalent oncologic outcomes, particularly for small, peripheral, subsolid
      nodules. However, for hypermetabolic nodules that are frequently associated with
      high rates of nodal disease, recurrence, or mortality, the optimum oncologic
      procedure was not assessed. We hypothesize that for hypermetabolic, cT1 N0
      adenocarcinoma, lobectomy and segmentectomy are associated with comparable
      outcomes. METHODS: A prospectively collected database was queried for patients
      with clinical stage IA lung adenocarcinoma who underwent lobectomy or
      segmentectomy (2000 to 2016) for hypermetabolic tumors (maximum standard uptake
      value [SUVmax] >= 3g/dL). To obtain balanced groups of patients, a propensity
      matching analysis was done. RESULTS: A total of 414 patients had hypermetabolic
      tumors and underwent lobectomy or segmentectomy. Patients were propensity matched
      (4:1) (lobectomy: n = 156, segmentectomy: n = 46). Patients in the lobectomy
      group had a higher rate of pathologic nodal upstaging (17% versus 7%, p = 0.085)
      and a higher pathologic upstaging rate (38% versus 26%, p = 0.143) than the
      segmentectomy group. In addition, the lobectomy group had a higher number of
      resected lymph nodes than the segmentectomy group (median lymph nodes resected:
      14 versus 7, p < 0.001). No differences were found in in 5-year recurrence-free
      survival (RFS; 72% versus 69%, p = 0.679) or in 5-year cancer-specific survival
      (CSS; 92% versus 83%, p = 0.557) between patients who underwent lobectomy or
      segmentectomy, respectively. CONCLUSIONS: Our data show that lobectomy and
      segmentectomy are comparable oncologic procedures for patients with carefully
      staged cT1 N0 lung adenocarcinoma with hypermetabolic tumors (SUVmax >= 3g/dL).
      Although lobectomy was associated with a more thorough lymph node dissection,
      this did not translate into a higher rate of RFS or CSS compared with
      segmentectomy.

PMID- 30240765
TI  - Valve Sparing Root Replacement Provides Similar Midterm Outcomes in Bicuspid and
      Trileaflet Valves.
AB  - BACKGROUND: Valve-sparing aortic root replacement (VSRR) is an established
      treatment for aortic root pathology for trileaflet valves. The safety and
      durability of VSRR in bicuspid aortopathy is unclear. In this study, outcomes of
      performing VSRR in the setting of bicuspid and trileaflet valves were compared.
      METHODS: An institutional database identified 294 patients who underwent VSRR
      from 2005 to 2017. Of these, 225 had trileaflet valves and 69 had bicuspid
      valves. Patients were followed prospectively and had annual postoperative
      echocardiograms. Propensity-matched comparisons were made between trileaflet and
      bicuspid valve patients. RESULTS: The average patient age for trileaflet valves
      was 46.0 +/- 13.5 versus 42.7 +/- 12.2 years for bicuspid patients (p = 0.07).
      There was a higher presence of preoperative >2+ aortic insufficiency (AI) present
      in bicuspid patients (63.8%) compared with trileaflet patients (31.1%) (p <
      0.01). Mean follow-up was 39 months and was 98% complete. At 5 years, the
      cumulative incidence of >2+ AI and aortic valve replacement (AVR) was 2.0% and
      4.3% in trileaflet patients and 7.7% (p = 0.75) and 7.7% (p = 0.81) in bicuspid
      patients. Preoperative >2+ AI was not predictive of >2+ postoperative AI (p =
      0.62) nor AVR (p = 0.49). Five-year survival was no different between groups
      (trileaflet: 98%, bicuspid: 84%, p = 0.24). CONCLUSIONS: VSRR can be safely and
      effectively performed in patients with trileaflet and bicuspid valves. Operative
      outcomes and valve function were equivalent in bicuspid and trileaflet patients
      in midterm follow-up. Performance of VSRR is a viable term option in the setting
      bicuspid aortic valve aortopathy.

PMID- 30240766
TI  - Graduate Subspecialty and Perceptions of Cardiothoracic Surgery Training: A 60
      Year Retrospective Study.
AB  - BACKGROUND: Recent initiatives in cardiothoracic (CT) surgery education have been
      aimed at early tracking, emphasizing specialization during the final years of
      residency. This study was performed to examine the impact of subspecialization on
      graduate assessment of quality of training and to identify educational gaps.
      METHODS: Surveys were sent to 119 surgeons who completed thoracic surgery
      residency at Washington University in St. Louis, Missouri between 1958 and 2017.
      Surveys evaluated transition-to-practice preparedness in patient care, technical
      skills, and qualifying and certifying examinations. A total of 78 surveys were
      returned complete, and 14 were returned "deceased" or "address unknown." Clinical
      practices included combined CT surgery (n = 22; 28%) and subspecialty cardiac (n
      = 28; 36%) or thoracic surgery (n = 28; 36%). Responses were quantified on five
      point Likert scales. Statistical analyses compared excellent (five points) with
      less than excellent (one to four points). RESULTS: Graduates who practiced
      combined CT surgery were more likely to report excellent preparation for
      qualifying examinations (cardiac, 60.7% vs thoracic, 35.7% vs CT, 86.4%; p =
      0.001) and certifying examinations (cardiac, 71.4% vs thoracic, 53.6% v. CT,
      86.4%; p = 0.042). Compared with thoracic surgery and combined CT surgery
      graduates, graduates who practiced cardiac surgery were more likely to indicate
      excellent preparation for performing adult cardiac surgery (cardiac, 85.2% vs
      thoracic, 34.8% vs CT, 81.8%; p < 0.001), although they felt least prepared to
      perform general thoracic surgery (cardiac, 85.7% vs thoracic, 100.0% vs CT,
      100.0%; p = 0.023). CONCLUSIONS: Graduates with combined CT surgery practices
      self-reported greater examination preparation and technical training compared
      with graduates who subspecialized in cardiac or thoracic surgery.
      Subspecialization led to perceived deficiencies among graduates in nonspecialty
      areas. This should be considered when developing new CT residency training
      paradigms.

PMID- 30240767
TI  - Totally Thorascopic Closure of the Left Atrial Appendage.
AB  - The left atrial appendage (LAA) is a major site of clot formation in atrial
      fibrillation. Stand-alone thoracoscopic LAA complete closure can decrease stroke
      risk and may be an alternative to life-long oral anticoagulation.1 We describe
      our technique for totally thoracoscopic LAA exclusion with an epicardial clip
      device. This approach provides a safe and likely more effective alternative to
      LAA management than other endocardial devices.

PMID- 30240768
TI  - Expression of the IDO1/TDO2-AhR pathway in tumor cells or the tumor
      microenvironment is associated with MCPyV status and prognosis in Merkel cell
      carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer,
      with approximately 80% of cases related to Merkel cell polyomavirus (MCPyV).
      Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) are
      the key rate-limiting enzymes of the tryptophan to kynurenine (KYN) metabolic
      pathway. With aryl hydrocarbon receptor (AhR), an intracellular transcription
      factor, they play a role in escaping the immunosurveillance process in several
      cancers. IDO1/TDO2/AhR expression associated with the MCPyV status and prognosis
      in MCC was investigated. Samples included 24 MCPyV-positive MCCs, 12 MCPyV
      negative MCCs with squamous cell carcinoma, and seven MCPyV-negative pure MCCs.
      They were stained immunohistochemically with IDO1, TDO2, and AhR antibodies and
      analyzed. Higher IDO1 expression in MCC tumor cells was found in MCPyV-negative
      than in MCPyV-positive MCC (P < .001). The tumor microenvironment (TME) in MCPyV
      negative MCC expressed higher TDO2 than MCPyV-positive MCC (P < .001). Kaplan
      Meier and log-rank tests showed that MCC with lower IDO1 expression in tumor
      cells and with lower TDO2 and AhR expressions in TME had better overall survival
      than otherwise (P = .043, .008, and .035, respectively); lower TDO2 expression in
      TME was also associated with longer disease-specific survival (P = .016). This
      suggests that IDO1, TDO2, and AhR express differentially in tumor cells or TME
      and play different roles in tumorigenesis between MCPyV-positive and -negative
      MCC that may affect the MCC biology. Evaluating IDO1/TDO2/AhR expression is
      important for selecting the most likely patients with MCC for immunotherapies
      targeting the IDO1/TDO2-AhR pathway.

PMID- 30240769
TI  - Clinicopathological significance of claspin overexpression and its association
      with spheroid formation in gastric cancer.
AB  - Gastric cancer (GC) is one of the leading causes of cancer-related death
      worldwide. Spheroid colony formation is a useful method to identify cancer stem
      cells (CSCs). The aim of this study was to identify a novel prognostic marker or
      therapeutic target for GC using a method to identify CSCs. We analyzed the
      microarray data in spheroid body-forming and parental cells and focused on the
      CLSPN gene because it is overexpressed in the spheroid body-forming cells in both
      the GC cell lines MKN-45 and MKN-74. Quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis revealed that CLSPN messenger RNA
      (mRNA) expression was upregulated in GC cell lines MKN-45, MKN-74, and TMK-1.
      Immunohistochemistry of claspin showed that 94 (47%) of 203 GC cases were
      positive. Claspin-positive GC cases were associated with higher T and N grades,
      tumor stage, lymphatic invasion and poor prognosis. In addition, claspin
      expression was co-expressed with CD44, human epidermal growth factor receptor
      type 2 (HER2) and p53. CLSPN small interfering RNA (siRNA) treatment decreased GC
      cell proliferation and invasion. These results indicate that the expression of
      claspin might be a key regulator in the progression of GC and might play an
      important role in CSCs of GC.

PMID- 30240770
TI  - Is revision of cut-off values needed when using CD3 immunohistochemical staining
      in histopathological diagnosis of lymphocytic colitis?
AB  - Lymphocytic colitis (LC) and lymphocytic colitis incomplete (LCi) are common
      causes of chronic watery diarrhea. The diagnosis relies on clinical findings and
      histopathological evaluation. The diagnostic criteria of LC are based on
      hematoxylin and eosin (HE) staining. However, supplementary immunohistochemical
      staining for highlighting the lymphocytes in borderline cases is now widely used.
      This change in diagnostics could lead to incorrectly diagnosing patients with LC
      and LCi if the present histological criteria are used. The number of
      intraepithelial lymphocytes (IELs) was estimated and categorized in intervals
      based on HE vs. CD3 stained slides from patients with a HE diagnose of normal
      colonic mucosa (n = 19), mucosa with non-specific reactive changes (n = 24), LCi
      (n = 24) and LC (n = 40). The number of IELs was compared with clinical symptoms.
      Overall, the number of IELs was higher with CD3 stain compared to HE stain in 73%
      of cases, unchanged in 26% of cases and lower in 1 case. The number of IELs
      detected was higher using the CD3 stain in 53%, 79%, 79% and 75% of cases
      included as normal colonic mucosa, non-specific reactive changes, LCi and LC,
      respectively. Based on CD3 stain 58% of the cases with non-specific reactive
      changes fulfilled the HE criteria for LCi and 79% of the cases with LCi fulfilled
      the HE criteria for LC. Automated image analysis of CD3 stained slides resulted
      in even higher numbers of IEL in all four diagnostic groups. Conclusively, our
      data support considering increased cut-off values for LCi and LC when assessed in
      CD3 stained specimens.

PMID- 30240771
TI  - Randomized controlled trial of monopolar cautery versus clips for staple line
      bleeding control in Roux-en-Y gastric bypass.
AB  - BACKGROUND: Bleeding from the staple line is a rare but serious problem following
      bariatric surgery. Staple line bleeding control (SLBC) can be achieved in
      different ways such as the application of sutures, clips, glue or buttressing
      materials over the staple line. Cauterization alone is generally not preferred
      due to concerns about debilitating the staple line. OBJECTIVES: The aim of this
      study was to compare the clip and monopolar cauterization methods for SLBC in
      laparoscopic Roux-en-Y gastric bypass. SETTING: University hospital. METHODS: A
      total of 70 morbidly obese patients were randomized into two groups. Patients
      with previous upper gastrointestinal surgery, re-do procedures and open surgeries
      were excluded. Their demographic characteristics, intraoperative and
      postoperative outcomes were examined. RESULTS: A total of 489 SLBC interventions
      (274 clips and 215 cauterizations) were performed after 280 stapling
      applications. SLBC intervention number and location, additional trocar
      requirement, blood loss and operation time were not different between the groups.
      In the clip group, two patients required monopolar cauterization when clipping
      failed. No intraabdominal bleeding or gastrointestinal leakage was seen in any
      group. Postoperative gastrointestinal hemorrhage was seen in three patients, two
      in the clip group and one in the cautery group. There was no difference between
      the groups in terms of postoperative pain score, abdominal drainage amount,
      hemoglobin level alteration, morbidity or length of stay. CONCLUSIONS: In
      laparoscopic Roux-en-Y gastric bypass, monopolar cauterization for SLBC can be
      used instead of clipping. It appears that monopolar cautery is a safe and
      effective approach for SLBC in laparoscopic Roux-en-Y gastric bypass.

PMID- 30240772
TI  - Mineral sunscreens not recommended by Consumer Reports: What lies beneath the
      surface?

PMID- 30240773
TI  - Prevention of Thermal Burns from Magnetic Resonance Imaging in Patients with
      Tattoos.

PMID- 30240774
TI  - Sirolimus for the treatment of "verrucous" venous malformation: are we missing
      the lymphatic malformation component?

PMID- 30240775
TI  - Predictors of Sentinel Lymph Node Positivity in Thin Melanoma Using the National
      Cancer Database.
AB  - BACKGROUND: Following melanoma excision, patients often receive sentinel lymph
      node biopsy (SLNB) for further staging. Limited data regarding predictors of SLNB
      positivity in thin melanoma are available. OBJECTIVE: To evaluate predictors of
      SLNB positivity in thin melanoma. METHODS: Patients with cutaneous melanoma,
      Breslow thickness <=1.00 mm who received a SLNB were identified from the National
      Cancer Database in the period from 2004-2014 (n=9,186). Predictors of SLNB
      positivity were analyzed using logistic regression. RESULTS: In a multivariate
      analysis, patients with age less than 60 (p<0.001) and Breslow thickness >0.8mm
      (p=0.03) were at increased risk for positive SLN. Moreover, on multivariate
      analysis, presence dermal mitoses increased odds of SLN positivity by 95% (OR
      1.95, 95%C 1.53-2.5, p<0.001), ulceration by 63% (OR 1.63, 95%CI 1.21-2.18,
      p<0.001) and Clark level IV-V by 48% (OR 1.48, 95%CI 1.19-1.85). Patients without
      ulceration but with dermal mitoses had 92% (OR 1.92, 95%CI 1.5-2.48, p<0.001)
      increased SLN positivity. LIMITATIONS: Limited survival data available.
      CONCLUSIONS: Younger age, Breslow thickness >0.8 mm, presence of dermal mitoses,
      ulceration and Clark level IV-V are positive predictors of positive SLN. While
      the new AJCC system has removed dermal mitotic rate from staging, continued
      evaluation of dermal mitotic rate could be valuable for guiding surgical decision
      making about SLNB.

PMID- 30240776
TI  - Cutaneous angioimmunoblastic T-cell lymphoma: Epstein-Barr Virus positivity and
      its effects on clinicopathological features.
AB  - BACKGROUND: Epstein-Barr virus (EBV) positivity frequently presents in patients
      with nodal angioimmunoblastic T-cell lymphoma (AITL). However, the presence of
      EBV in skin lesions and its clinicopathological significance have not been
      evaluated. OBJECTIVE: To analyze the clinical and histopathological features of
      cutaneous AITL and evaluate EBV-positivity in skin tissue and its effects on
      clinicopathological features of AITL. METHODS: Clinicopathological variables in
      patients with cutaneous AITL were analyzed and compared depending on EBV in situ
      hybridization status in skin lesions using the patients' medical records.
      RESULTS: Of the 86 patients with AITL, 42 had a cutaneous presentation.
      Positivity for and EBV in situ hybridization was noted in 19 of 42 patients with
      cutaneous AITL. EBV positivity was more common in papule or nodular skin lesions
      compared to other cutaneous morphologies, such as non-specific rash or purpuric
      patches. Positive EBV in situ hybridization was associated with a pattern of
      dense superficial and deep infiltrates of pleomorphic large sized, atypical
      lymphocytes. EBV positivity in skin lesions was an independent negative
      prognostic factor in patients with AITL. LIMITATIONS: Retrospective study at a
      single institution. CONCLUSION: EBV-positive cutaneous AITL is associated with
      distinctive clinicopathological features.

PMID- 30240777
TI  - Reply.

PMID- 30240778
TI  - Barriers to Compounding in Physician Offices: The Future is Now!

PMID- 30240779
TI  - Global Epidemiology and Clinical Spectrum of Rosacea, Highlighting Skin of Color:
      Review and Clinical Practice Experience.
AB  - Among individuals with skin of color, rosacea has been reported less frequently
      than in those with white skin, but it is not a rare disease. In fact, rosacea may
      be underreported and underdiagnosed in populations with skin of color because of
      the difficulty of discerning erythema and telangiectasia in dark skin, as well as
      underestimation of the susceptibility of more highly pigmented skin to
      dermatologic conditions like rosacea whose triggers include sun exposure. Many
      people with skin of color who have rosacea may experience delayed diagnosis
      leading to inappropriate or inadequate treatment, greater morbidity, and
      uncontrolled, progressive disease with disfiguring manifestations, including
      phymatous rosacea. This paper reviews the epidemiology of rosacea in skin of
      color and highlights variations in the clinical presentation of rosacea across
      the diverse spectrum of patient populations affected. It presents strategies to
      aid in the timely diagnosis and effective treatment of rosacea in patients with
      skin of color, with an aim of promoting increased awareness of rosacea in these
      patients and reducing disparities in the management of their disease.

PMID- 30240780
TI  - Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and
      systemic symptoms (DRESS) severity score: A useful tool for assessing disease
      severity and predicting fatal cytomegalovirus disease.
AB  - BACKGROUND: The prognosis of drug-induced hypersensitivity syndrome (DiHS)/drug
      reaction with eosinophilia and systemic symptoms (DRESS) is highly unpredictable.
      Severe complications, either related or unrelated to cytomegalovirus (CMV)
      reactivation, are highly probable cause of death. OBJECTIVES: The aim was to
      establish a scoring system for DiHS/DRESS that can be used to monitor severity,
      predict the prognosis, and to stratify the risk of developing CMV disease and
      complications. METHODS: A retrospective analysis of 55 patients with DiHS/DRESS
      was performed. A composite score was created using clinical data. DiHS/DRESS
      patients were also stratified into three groups based on the scores to predict
      the risk of CMV reactivation and complications. RESULTS: This scoring system made
      it possible to predict CMV disease and complications. Scores >= 4 were associated
      with the later development of CMV disease and complications, while no patients
      with scores < 4 developed complications. LIMITATION: A single-institutional study
      with a relatively small patient cohort, lacking a validation cohort. CONCLUSIONS:
      Our scoring system may be useful for predicting CMV-related complications and
      early intervention with anti-CMV agents should be considered in patients with
      scores >=4 and/or evidence of CMV reactivation.

PMID- 30240781
TI  - TP003 is a non-selective benzodiazepine site agonist that induces anxiolysis via
      alpha2GABAA receptors.
AB  - Benzodiazepines (BDZ), which potentiate the action of GABA at four subtypes of
      GABAA receptors (alpha1, alpha2, alpha3, and alpha5GABAARs), are highly effective
      against anxiety disorders, but also cause severe side effects greatly limiting
      their clinical application. Both, preclinical studies in genetically engineered
      mice, and preclinical and clinical trials with subtype-selective compounds
      indicate that undesired effects can in principle be avoided by targeting specific
      GABAAR subtypes. While there is general consensus that activity at alpha1GABAARs
      should be avoided, controversy exists as to whether alpha2 or alpha3GABAARs need
      to be targeted for anxiolysis. While previous experiments in GABAAR point-mutated
      mice demonstrated a critical role of alpha2GABAARs, studies solely relying on
      pharmacological approaches suggested a dominant contribution of alpha3GABAARs. As
      most alpha1GABAAR-sparing BDZ site agonists discriminate little between alpha2
      and alpha3GABAARs, these claims rest almost exclusively on a single compound,
      TP003, that has been reported to be a selective alpha3GABAAR modulator. Here, we
      have revisited the in vitro pharmacological profile of TP003 and, in addition,
      tested TP003 in GABAAR triple point-mutated mice, in which only either alpha1,
      alpha2, or alpha3GABAARs were left BDZ sensitive. These experiments revealed that
      TP003 behaves as a partial, rather non-selective BDZ site agonist in vitro that
      acts in vivo through alpha1, alpha2, and alpha3GABAARs (alpha5GABAAR-mediated
      effects were not tested). With respect to anxiolysis, our results support a
      critical contribution of alpha2GABAARs, but not of alpha3GABAARs. TP003 should
      therefore not be considered an alpha3GABAAR selective agent. Previously published
      studies using TP003 should be interpreted with caution.

PMID- 30240782
TI  - Acute inflammation sensitizes knee-innervating sensory neurons and decreases
      mouse digging behavior in a TRPV1-dependent manner.
AB  - Ongoing, spontaneous pain is characteristic of inflammatory joint pain and
      reduces an individual's quality of life. To understand the neural basis of
      inflammatory joint pain, we made a unilateral knee injection of complete Freund's
      adjuvant (CFA) in mice, which reduced their natural digging behavior. We
      hypothesized that sensitization of knee-innervating dorsal root ganglion (DRG)
      neurons underlies this altered behavior. To test this hypothesis, we performed
      electrophysiological recordings on retrograde labeled knee-innervating primary
      DRG neuron cultures and measured their responses to a number of electrical and
      chemical stimuli. We found that 24-h after CFA-induced knee inflammation, knee
      neurons show a decreased action potential generation threshold, as well as
      increased GABA and capsaicin sensitivity, but have unaltered acid sensitivity.
      The inflammation-induced sensitization of knee neurons persisted for 24-h in
      culture, but was not observed after 48-h in culture. Through
      immunohistochemistry, we showed that the increased knee neuron capsaicin
      sensitivity correlated with enhanced expression of the capsaicin receptor,
      transient receptor potential vanilloid 1 (TRPV1) in knee-innervating neurons of
      the CFA-injected side. We also observed an increase in the co-expression of TRPV1
      with tropomyosin receptor kinase A (TrkA), which is the receptor for nerve growth
      factor (NGF), suggesting that NGF partially induces the increased TRPV1
      expression. Lastly, we found that systemic administration of the TRPV1
      antagonist, A-425619, reversed the decrease in digging behavior induced by CFA
      injection, further confirming the role of TRPV1, expressed by knee neurons, in
      acute inflammatory joint pain.

PMID- 30240783
TI  - Modality selective roles of pro-nociceptive spinal 5-HT2A and 5-HT3 receptors in
      normal and neuropathic states.
AB  - Descending brainstem control of spinal nociceptive processing permits a dynamic
      and adaptive modulation of ascending sensory information. Chronic pain states are
      frequently associated with enhanced descending excitatory drive mediated
      predominantly through serotonergic neurones in the rostral ventromedial medulla.
      In this study, we examine the roles of spinal 5-HT2A and 5-HT3 receptors in
      modulating ascending sensory output in normal and neuropathic states. In vivo
      electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and
      sham-operated rats to record from wide dynamic range neurones in the ventral
      posterolateral thalamus. In sham rats, block of spinal 5-HT3Rs with ondansetron
      revealed tonic facilitation of noxious punctate mechanical stimulation, whereas
      blocking 5-HT2ARs with ketanserin had minimal effect on neuronal responses to
      evoked stimuli. The inhibitory profiles of both drugs were altered in SNL rats;
      ondansetron additionally inhibited neuronal responses to lower intensity punctate
      mechanical stimuli and noxious heat evoked responses, whereas ketanserin
      inhibited innocuous and noxious evaporative cooling evoked responses. Neither
      drug had any effect on dynamic brush evoked responses nor on spontaneous firing
      rates in both sham and SNL rats. These data identify novel modality and intensity
      selective facilitatory roles of spinal 5-HT2A and 5-HT3 receptors on sensory
      neuronal processing within the spinothalamic-somatosensory cortical pathway.

PMID- 30240785
TI  - Geranylgeranylacetone blocks the reinstatement of morphine-conditioned place
      preference.
AB  - Morphine is widely used for clinical pain management and induces the dependence.
      Addiction to morphine is a major public health issue. Geranylgeranylacetone (GGA)
      is widely used in clinic for treating ulcer. GGA induces expression of
      thioredoxin-1 (Trx-1) extensively. Trx-1 is a redox regulating protein and plays
      protecting roles in nervous system. GGA prevents mice against morphine-induced
      hyperlocomotion, rewarding effect, and withdrawal syndrome. However, whether GGA
      blocks morphine-conditioned place preference (CPP) reinstatement is still
      unknown. In the present study, we found that GGA administration blocked the
      reinstatement of morphine-CPP. The expressions of Trx-1, N-methyl d-aspartate
      receptor 2B subunit (NR2B), phosphorylated Ca2+/calmodulin-dependent protein
      kinase II (p-CaMKII), phosphorylated extracellular signaling regulated kinases (p
      ERK), and phosphorylated cAMP-response element binding protein (p-CREB) were
      induced in nucleus accumbens (NAc) and hippocampus by morphine or GGA, whereas
      these proteins were not changed by morphine in GGA-treated mice. Our results
      indicate that GGA may prevent the reinstatement of morphine-CPP through
      strengthening the expression of Trx-1 and regulating NR2B/ERK pathway. Thus, we
      suggest that GGA may be a promising therapeutic candidate for morphine-induced
      relapse.

PMID- 30240786
TI  - Comparative comprehension on the anti-rheumatic Chinese herbal medicine
      Siegesbeckiae Herba: Combined computational predictions and experimental
      investigations.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Siegesbeckiae Herba (SH) is a traditional anti
      rheumatic herbal medicine in China. The SH-derived product is the first licensed
      traditional herbal medicinal product for the management of rheumatism-induced
      joint and muscle pain in United Kingdom. The authenticated plant origins listed
      in the official Chinese Pharmacopeia for SH include Siegesbeckia orientalis L.
      (SO), S. pubescens Markino (SP) and S. glabrescens Markino (SG). Although the
      therapeutic effects of these SH species in treating rheumatoid arthritis (RA) are
      similar, their difference in chemical profiles suggested their anti-rheumatisms
      mechanisms and effects may be different. AIM OF THE STUDY: This study was
      designed to comparatively comprehend the chemical and biological similarity and
      difference of SO, SP and SG for treating rheumatoid arthritis based on the
      combination of computational predictions and biological experiment
      investigations. MATERIALS AND METHODS: The reported compounds for SO, SP and SG
      were obtained from four chemical databases (SciFinder, Combined Chemical
      Dictionary v2009, Dictionary of Natural Products and Chinese academy of sciences
      Chemistry Database). The RA-relevant proteins involved in nuclear factor-kappa B
      (NF-kappaB), oxidative stress and autophagy signaling pathways were collected
      from the databases of Kyoto Encyclopedia of Genes and Genomes and Biocarta. The
      comparative comprehension of SH plants was performed using similarity analysis,
      molecular docking and compounds-protein network analysis. The chemical
      characterization of different SH extracts were qualitatively and quantitatively
      analyzed, and their effects on specific RA-relevant protein expressions were
      investigated using Western blotting analysis. RESULTS: Chemical analysis revealed
      that SO contains mainly sequiterpenes and pimarenoids; SP contains mainly
      pimarenoids, sequiterpenes, and kaurenoids; and SG contains mainly pimarenoids,
      flavonoids and alkaloids. Moreover, coincided with the predicted results from
      computational analysis, different SH species were observed to present different
      chemical constituents, and diverse effects on RA-relevant proteins at the
      biological level. CONCLUSIONS: The chemical and biological properties of SO, SP
      and SG were different and distinctive. The systematic comparison between these
      three confusing Chinese herbs provides reliable characterization profiles to
      clarify the pharmacological substances in SH for the precise management of
      rheumatism/-related diseases in clinics.

PMID- 30240787
TI  - Effects of regional hypoxia and incubation temperature on growth,
      differentiation, heart mass, and oxygen consumption in embryos of the leopard
      gecko (Eublepharis macularius).
AB  - Oviparous reptile embryos must tolerate fluctuations in oxygen availability and
      incubation temperature during development. In this study, regional hypoxia was
      simulated by painting eggs of Eublepharis macularius with melted paraffin wax to
      decrease the available surface area for gas exchange by approximately 80%.
      Experimental and control eggs were incubated at either 28 or 34  degrees C and
      embryo mass, stage, heart mass, relative heart mass, and oxygen consumption (VO2)
      were measured at 15 and 30 days of incubation. Embryo mass from the regional
      hypoxia treatment was reduced by about 50% at day 15 and by about 30% at day 30
      of incubation, independent of incubation temperature compared to controls. Embryo
      stage from the regional hypoxia treatment was reduced by about 2 stages at day 15
      independent of incubation temperature but there was no effect of hypoxia
      treatment at day 30. Absolute heart mass was reduced by about 60% in regional
      hypoxia embryos sampled at day 15 while relative heart mass was increased by
      about 30% in regional hypoxic embryos at day 30 compared to controls, suggesting
      that heart mass is conserved at the expense of somatic growth. Embryo VO2 was
      affected by incubation temperature at both 15 and 30 days of incubation but not
      by regional hypoxia treatment. These results indicate that embryos of E.
      macularius possess plasticity in their capacity to respond to reduction in oxygen
      availability during incubation, and are able to survive and continue developing
      when gas exchange surface area is severely limited.

PMID- 30240784
TI  - Orexin 2 receptor stimulation enhances resilience, while orexin 2 inhibition
      promotes susceptibility, to social stress, anxiety and depression.
AB  - Knockdown of orexin/hypocretin 2 receptor (Orx2) in the basolateral amygdala
      (BLA) affects anxious and depressive behavior. We use a new behavioral paradigm,
      the Stress Alternatives Model (SAM), designed to improve translational impact.
      The SAM induces social stress in adult male mice by aggression from larger mice,
      allowing for adaptive decision-making regarding escape. In this model, mice
      remain (Stay) in the oval SAM arena or escape from social aggression (Escape) via
      routes only large enough for the smaller mouse. We hypothesized
      intracerebroventricular (icv) stimulation of Orx2 receptors would be anxiolytic
      and antidepressive in SAM-related social behavior and the Social
      Interaction/Preference (SIP) test. Conversely, we predicted that icv antagonism
      of Orx2 receptors would promote anxious and depressive behavior in these same
      tests. Anxious behaviors such as freezing (both cued and conflict) and startle
      are exhibited more often in Stay compared with Escape phenotype mice. Time spent
      attentive to the escape route is more frequent in Escape mice. In Stay mice,
      stimulation of Orx2 receptors reduces fear conditioning, conflict freezing and
      startle, and promotes greater attention to the escape hole. This anxiolysis was
      accompanied by activation of a cluster of inhibitory neurons in the amygdala. A
      small percentage of those Stay mice also begin escaping; whereas Escape is
      reversed by the Orx2 antagonist. Escape mice were also Resilient, and Stay mice
      Susceptible to stress (SIP), with both conditions reversed by Orx2 antagonism or
      stimulation respectively. Together, these results suggest that the Orx2 receptor
      may be a useful potential target for anxiolytic or antidepressive therapeutics.

PMID- 30240788
TI  - Functional analysis of MoSnf7 in Magnaporthe oryzae.
AB  - Snf7 is the core subunit protein of the yeast endosomal sorting complex required
      for transport (ESCRT) complex, which plays important roles in endocytosis and
      autophagy. In this study, we characterized MoSnf7 in Magnaporthe oryzae, a
      homolog of yeast Snf7, the core protein of ESCRT-III subcomplex. Like Snf7,
      MoSnf7 also localizes next to the vacuoles. Deletion of MoSNF7 resulted in
      significant decrease in vegetative growth and pathogenicity. Further analyses of
      DeltaMosnf7 mutants showed that they were defective in endocytosis, sexual and
      asexual development, turgor pressure maintenance of appressorium at hyphal tips,
      and cell wall integrity. Additional assays for the localization and degradation
      of GFP-MoAtg8 in DeltaMosnf7 mutants showed that they were defective in autophagy
      pathway. Based on the roles of yeast Snf7 in endocytosis and autophagy, we
      propose that the decreased vegetative growth and pathogenicity of DeltaMosnf7
      rice blast fungus M. oryzae, was partly due to the conservative roles of MoSnf7
      in vesicle trafficking and autophagy pathway.

PMID- 30240789
TI  - Mgm1 is required for maintenance of mitochondrial function and virulence in
      Candida albicans.
AB  - Mitochondria are dynamic organelles, and their shapes and sizes are regulated by
      mitochondrial fusion and fission. The proteins essential for mitochondrial fusion
      in Candida albicans have not been clearly characterized. In this study, Mgm1 was
      explored for its roles in mitochondrial function, cell cycle, hyphal growth and
      virulence in this pathogen. The deletion of MGM1 led to mitochondrial
      fragmentation and mtDNA loss and activated the checkpoint pathway to arrest the
      cell cycle in G1 phase. Moreover, loss of MGM1 led to defects in hyphal
      development and attenuation of virulence in a macrophage cell line and a mouse
      model of disseminated infection. These results reveal that Mgm1 plays an
      important role in mitochondrial dynamics and function, cell cycle progression,
      hyphal development and virulence in C. albicans.

PMID- 30240790
TI  - Comparison of plication and resection in large-angle exotropia.
AB  - BACKGROUND: Plication of the rectus muscles is used sparingly as a tightening
      procedure compared to resection, however, the relative efficacy of these
      procedures is difficult to assess because the sparse literature comparing the two
      is further limited by a lack of imaging. This case series attempts to compare the
      techniques in cases of exotropia along with quantitative assessment of ultrasound
      biomicroscopy (UBM). METHODS: Patients with exotropia of 30Delta-50Delta who had
      undergone first-time horizontal strabismus surgery were recruited and
      prospectively underwent UBM evaluation 1 year after surgery. Plication was
      performed by folding the anterior part of the medial rectus muscle posteriorly
      and tying it at the insertion to the sclera. Resection was performed in a routine
      manner. Deviation and motility were assessed postoperatively, when UBM was
      performed. Only patients with basic comitant exotropia without any vertical
      pattern were included. RESULTS: During the study period, 15 patients underwent
      resection of the medial rectus and 13 underwent plication. The two groups were
      age and deviation matched preoperatively. The patients undergoing plication and
      resection fared equally in terms of postoperative deviation (P = 0.81) and
      abduction limitation (P = 0.169). UBM could identify and quantify plication in
      all cases with excellent agreement with the operative data (intraclass
      correlation coefficient = 0.886; P = 0.000). CONCLUSIONS: Medial rectus plication
      or resection performed for similar angles of exotropia produced quantitatively
      similar results. Plication offered the advantage of being characteristically
      identifiable and measurable on UBM.

PMID- 30240791
TI  - Long-Term Regular Use of Low-Dose Aspirin and Neovascular Age-Related Macular
      Degeneration: National Sample Cohort 2010-2015.
AB  - PURPOSE: The association between long-term cardioprotective aspirin use and
      neovascular age-related macular degeneration (AMD) is controversial. This study
      was undertaken to estimate the risk of neovascular AMD with long-term regular use
      of low-dose aspirin. DESIGN: Retrospective population-based study, using a
      nationwide cohort from a variety of clinics and hospitals in South Korea.
      PARTICIPANTS: Nonregular aspirin users and regular aspirin users under national
      health insurance, aged >=45 years, who were followed from 2010 to 2015, were
      identified. METHODS: Incidence per 10 000 person-years for neovascular AMD was
      estimated. Long-term regular use of low-dose aspirin was defined as sustained
      intake of <=100 mg aspirin with >=1044 days prescription between 2005 and 2009.
      Nonregular aspirin users included occasional users or nonusers. The analyses
      included a propensity score-adjusted analysis in a large, randomly selected,
      unmatched whole cohort (n = 482 613); propensity score-matched analysis in a
      matched cohort (n = 74 196); and maximally adjusted analysis in the unmatched
      whole cohort (n = 482 613). MAIN OUTCOME MEASURES: Incidence of newly developed
      neovascular AMD using the registration code for intractable disease under
      national health insurance. RESULTS: Incidence of neovascular AMD was 3.5 among
      nonregular aspirin users and 7.2 among regular aspirin users per 10 000 person
      years in the unmatched whole cohort. However, propensity score-adjusted analyses
      revealed no association between aspirin use and neovascular AMD (adjusted hazard
      ratio [HR], 0.98; 95% confidence interval [CI], 0.73-1.30). Likewise, propensity
      score-matched analyses showed no association; incidences of neovascular AMD were
      7.5 and 7.1 among nonregular aspirin users and regular aspirin users (crude HR,
      0.94; 95% CI, 0.70-1.28), respectively. A maximally adjusted model, including
      age, sex, income, residential area, and history of 100 randomly selected types of
      generic drugs, showed no association (adjusted HR, 0.95; 95% CI, 0.71-1.28).
      CONCLUSIONS: We found no association between long-term regular use of low-dose
      aspirin for 5 years and future incidence of neovascular AMD. Thus, this large
      scale study suggests that regular, long-term use of low-dose aspirin appears to
      be safe with respect to the new development of neovascular AMD.

PMID- 30240792
TI  - Setting the Gold(en) Standard for Ethical Care: #PatientCommunication.

PMID- 30240793
TI  - SGLT1 inhibition: Pros and cons.
AB  - Sodium Glucose Cotransporters 1 (SGLT1) play important roles in the intestinal
      absorption of glucose and the renal reabsorption of glucose, especially in
      patients with uncontrolled diabetes and those receiving SGLT2 inhibitors. As a
      consequence, the inhibition of SGLT1 transporters may represent an interesting
      therapeutic option in patients with diabetes. However, genetic models of SGLT1
      inactivation indicate that the malfunction of these transporters may have adverse
      effects on various tissues. In this review, we discuss the available evidence on
      the beneficial and detrimental effects that the inhibition of SGLT1 transporters
      might have. The inhibition of SGLT1 lowers serum glucose levels through the
      inhibition of intestinal absorption and renal reabsorption of glucose. In
      addition, drugs that interfere with SGLT1-mediated transport of glucose may
      protect cardiac tissue by reducing glycogen accumulation and decreasing the
      production of reactive oxygen species. On the other hand, this strategy may
      result in diarrhea, volume depletion, may interfere with the correction of
      hypoglycemia through the oral administration of carbohydrates and could
      predispose to the development of euglycemic diabetic ketoacidosis. Therefore, at
      the moment, SGLT1 inhibition seems to represent a two-edged sword.

PMID- 30240794
TI  - Role of Oleanolic acid in maintaining BBB integrity by targeting p38MAPK/VEGF/Src
      signaling pathway in rat model of subarachnoid hemorrhage.
AB  - Vasogenic brain edema after subarachnoid hemorrhage (SAH) is an independent risk
      factor for death and poor prognosis. Disruption of the blood-brain barrier (BBB)
      is the main cause of vasogenic brain edema induced by SAH. Oleanolic acid (OA) is
      a natural pentacyclic triterpenoid with various biological functions. Previous
      studies have shown that prophylactic administration of OA could prevent the BBB
      disruption in autoimmune encephalomyelitis mice. In this context, we speculate
      that OA may play a neuroprotective role by protecting the integrity of the BBB
      and reducing vasogenic cerebral edema after SAH. To validate this hypothesis, a
      SAH model was established on Sprague Dawley rats using a standard intravascular
      puncture model. The effects of OA on various physiological indexes were observed,
      including SAH grades, mortality, neurological function score, brain edema and BBB
      permeability. Related proteins of the brain endothelial cell junction complex
      were also detected, including tight junctions (TJs) and adherent junctions (AJs).
      Results showed that OA significantly reduced the permeability of BBB and relieved
      brain edema by increasing protein expression of TJs and AJs, and decreased the
      SAH grades by increasing the protein expression of heme oxygenase-1 (HO-1) in SAH
      rats. Additionally, we found OA could inhibit up-regulation of VEGF and the
      phosphorylation of p38 mitogen-activated protein kinase (MAPK), and suppress
      p38MAPK/VEGF/Src signaling pathway which involved in BBB disruption following
      SAH. From the experimental results, we speculate that OA effectively alleviated
      SAH-induced vasogenic edema by targeting p38 MAPK/VEGF/Src axis.

PMID- 30240795
TI  - Precision medicine approach: Empagliflozin for diabetic cardiomyopathy in mice
      with aldehyde dehydrogenase (ALDH) 2 * 2 mutation, a specific genetic mutation in
      millions of East Asians.
AB  - A vast majority of type-2 diabetic patients (~65%) die of cardiovascular
      complications including heart failure (HF). In diabetic hearts, levels of 4
      hydroxy-2-nonenal (4HNE), a reactive aldehyde that is produced upon lipid
      peroxidation, were increased. We also demonstrated that in diabetic hearts, there
      is a decrease in the activity of aldehyde dehydrogenase (ALDH) 2, a primary
      detoxifying enzyme present in cardiac mitochondria. A single point mutation at
      E487K of ALDH2 in East Asians known as ALDH2 * 2 intrinsically lowers ALDH2
      activity. We hypothesize that Empagliflozin (EMP), a sodium-glucose cotransporter
      (SGLT) 2 inhibitor, can ameliorate diabetic cardiomyopathy by decreasing
      hyperglycemia-mediated 4HNE protein adducts in ALDH2 * 2 mutant mice which serve
      as a precision medicine tool as they mimic ALDH2 * 2 carriers. We induced type-2
      diabetes in 11-14 month-old male and female ALDH2 * 2 mice through a high-fat
      diet. Chow-fed ALDH2 * 2 mice served as controls. At the end of 4 months, we
      treated the diabetic ALDH2 * 2 mice with EMP (3 mg/kg/d) or its vehicle (Veh).
      After 2 months of EMP treatment, cardiac function was assessed by conscious
      echocardiography after treadmill exercise stress. EMP improved the cardiac
      function and running distance and duration significantly compared to Veh-treated
      ALDH2 * 2 diabetic mice. These beneficial effects can be attributed to the EMP
      mediated decrease in cardiac mitochondrial 4HNE adducts and increase in the
      levels of phospho AKT, AKT, phospho Akt substrate of 160 kDa (pAS160), AS160 and
      GLUT-4 in the skeletal muscle tissue of the ALDH2*2 mutant diabetic mice,
      respectively. Finally, our data implicate EMP can ameliorate diabetic
      cardiomyopathy in diabetic ALDH2 * 2 mutant patients.

PMID- 30240796
TI  - Resveratrol down-regulates endothelin type B receptors in vascular smooth muscle
      cells via Sirt1/ERK1/2/NF-kB signaling pathways.
AB  - Silent information regulator family protein 1 (Sirt1) has gained attention for
      protective effects against cardiovasc diseases. Vascular smooth muscle endothelin
      type B (ETB) receptors are related to the pathogenesis of cardiovascular
      diseases. Elevated oxidized low-density lipoprotein (ox-LDL) is associated with
      atherosclerosis. This study will investigate whether resveratrol (a Sirt1
      activator, Res) is involved in oxidized low density lipoprotein (ox-LDL)-mediated
      regulation of ETB receptors in rat superior mesenteric arteries (SMA). The rat
      SMA segments were cultured in the presence and absence of ox-LDL with or without
      Res and specific inhibitor (U0126) for the extracellular signal-regulated protein
      kinase 1 and 2 (ERK1/2) for 24 h. After organ culture, the contractile responses
      to sarafotoxin 6c (S6c) were studied using a sensitive myograph, and the ETB
      receptor protein expression was detected using Western blotting. The results
      showed that Res concentration-dependently suppressed the ox-LDL -induced up
      regulation of ETB receptors expression and receptor-mediated vasoconstriction. In
      addition, these effects could be inhibited by U0126. Furthermore, activity of
      ERK1/2 phosphorylation and P65 acetylation induced by ox-LDL were blocked by Res.
      In conclusion, Res down-regulated ETB receptors through up-regulating Sirt1 and
      followed by ERK1/2/NF-kB signaling pathways in the organ culture SMA.

PMID- 30240797
TI  - Anticoagulation in elderly patients with nonvalvular atrial fibrillation: A
      balancing act.

PMID- 30240798
TI  - Retrograde venous ethanol ablation for ventricular tachycardia.

PMID- 30240799
TI  - Electrical parameters for physiological His-Purkinje pacing vary by implant
      location in an ex vivo canine model.
AB  - BACKGROUND: Permanent His-bundle pacing (HBP) is an attractive, perhaps more
      physiological, alternative to traditional right ventricular pacing. OBJECTIVE:
      The purpose of this study was to utilize direct visualization to more
      comprehensively understand the anatomy central to HBP, correlating electrical
      lead performance to implant locations along the His-bundle (HB) pathway. METHODS:
      Canine hearts (n = 5) were isolated and reanimated using Visible Heart
      methodologies. Medtronic 3830 SelectSecure leads were fixated where His
      potentials were present. The location of each implant was mapped/binned into 4
      regions approximately analogous to the proximal, penetrating, and distal HB.
      Locational differences in HBP capture and resultant QRS morphology were assessed.
      RESULTS: Average HBP capture thresholds did not significantly vary with respect
      to implant location (1.0-ms pulse width; P = .48). The resulting QRS morphologies
      from HB-paced beats varied in relation to implant location. As leads were placed
      further distally along the HB, the ratio of paced to native QRS complex duration
      increased (DeltaQRSpaced/DeltaQRSnative ratios-region 2: 0.84 +/- 0.16; region 3:
      1.04 +/- 0.42; region 4: 1.74 +/- 0.86). CONCLUSION: We demonstrated correlation
      between the anatomic locations of HBP lead placement and resultant QRS
      morphologies in a reanimated canine heart model. Proximal placement along the HB
      pathway resulted in more favorable QRS morphologies, suggesting improved
      selective HBP capture, with no significant increase in HBP capture thresholds.
      Pacing the HB in more proximal pathway locations improved the selectivity of HBP
      and may confer electrical and anatomic benefits relative to distal HBP.

PMID- 30240800
TI  - Botulinum toxin injection in the autonomic ganglion plexi to prevent
      postoperative atrial fibrillation: More than a cosmetic treatment.

PMID- 30240801
TI  - The growth performance and nonspecific immunity of loach Paramisgurnus dabryanus
      as affected by dietary beta-1,3-glucan.
AB  - Four diets supplemented with three different levels of beta-1,3-glucan (0.5, 1,
      and 2 g kg-1) were formulated and tested for growth, intestine digestive-enzyme
      activities, PO, SOD and GPx activities and erythrocytes number, phagocytic
      percentage of erythrocytes and lysozyme activity and resistance to Aeromonas
      hydrophila of loach Paramisgurnus dabryanus. A diet without any beta-1,3-glucan
      served as the control. After 60 days of feeding, the growth performance,
      intestine digestive-enzyme activities, nonspecific immunity, and resistance to
      Aeromonas hydrophila of P. dabryanus were higher than those of the control when
      the loaches P. dabryanus were fed with beta-1,3-glucan-containing diets. Results
      revealed that dietary beta-1,3-glucan can improve the growth performance,
      intestine digestive-enzyme activities, PO, SOD and GPx activities and
      erythrocytes number, phagocytic percentage of erythrocytes and lysozyme activity
      and resistance of loaches P. dabryanus and can thus be used as their diet
      supplement.

PMID- 30240802
TI  - Identification of Caspase-6 and Caspase-7 from miiuy croaker and evolution
      analysis in fish.
AB  - Apoptosis is a basic biological phenomenon of cells, which is an important
      component in the evolution of organisms, the stabilization of the internal
      environment and the development of multiple systems. In addition, the caspase
      protein family plays an important role in these pathways of apoptosis. Among
      them, apoptotic executors can directly act on specific substrates to complete the
      apoptotic response. In this study, we identified the Caspase-6 and Caspase-7
      genes of miiuy croaker, and then analyzed the evolution of the whole Caspase
      family, furthermore described the evolutionary selection sites of the caspase-6
      and caspase-7 genes in fish. The results showed that Caspase-6 gene appeared
      earlier than Caspase-7 in species evolution and gene duplication in teleost fish.
      Moreover, we also found that caspase-6 gene had no potential positive selection
      sites in the evolution of fish. Unlike the caspase-6 gene, the caspase-7 gene did
      not appear to be missed or replicated during the evolution of the species, while,
      it to be found two potential positive selection sites.

PMID- 30240803
TI  - Factorization machines and deep views-based co-training for improving answer
      quality prediction in online health expert question-answering services.
AB  - In online health expert question-answering (HQA) services, it is significant to
      automatically determine the quality of the answers. There are two prominent
      challenges in this task. First, the answers are usually written in short text,
      which makes it difficult to absorb the text semantic information. Second, it
      usually lacks sufficient labeled data but contains a huge amount of unlabeled
      data. To tackle these challenges, we propose a novel deep co-training framework
      based on factorization machines (FM) and deep textual views to intelligently and
      automatically identify the quality of HQA systems. More specifically, we exploit
      additional domain-specific semantic information from domain-specific word
      embeddings to expand the semantic space of short text and apply FM to excavate
      the non-independent interaction relationships among diverse features within
      individual views for improving the performance of the base classifier via co
      training. Our learned deep textual views, the convolutional neural networks (CNN)
      view which focuses on extracting local features using convolution filters to
      locally model short text and the dependency-sensitive convolutional neural
      networks (DSCNN) view which focuses on capturing long-distance dependency
      information within the text to globally model short text, can then overcome the
      challenge of feature sparseness in the short text answers from the doctors. The
      developed co-training framework can effectively mine the highly non-linear
      semantic information embedded in the unlabeled data and expose the highly non
      linear relationships between different views, which minimizes the labeling
      effort. Finally, we conduct extensive empirical evaluations and demonstrate that
      our proposed method can significantly improve the predictive performance of the
      answer quality in the context of HQA services.

PMID- 30240804
TI  - Influence of imputation strategies on the identification of brain functional
      connectivity networks.
AB  - Whenever neurophysiological data, such as EEG data are recorded, occurring
      artifacts pose an essential problem. This study addresses this issue by using
      imputation methods whereby whole data sets of a trial, or distinct electrodes,
      are not removed from the analysis of the EEG data but are replaced. We present
      different imputation strategies but use only two which are optimal for this
      particular study; predictive mean matching and data augmentation. The study
      addresses the as of yet unresolved question if the quality of derived brain
      functional networks is improved by imputation methods compared to traditional
      exclusion techniques which drop data, and will finally assesses the differences
      between the two imputation methods themselves used here. In this study, EEG data
      from a study evaluating dyslexia-specific therapy on a neurophysiological level
      were used to investigate imputation strategies in research of cortical
      interaction. Several recorded values were artificially declared as 'missing'.
      This enables the comparison of networks based on the complete data set without
      any missing values (pseudo ground truth) and those derived from imputation
      approaches in a realistic situation of disturbed data. Functional connectivity
      was quantified by time-variant partial directed coherence, providing a directed,
      temporally varying and frequency-selective connectivity measure. Based on the
      comparison between pseudo ground truth and networks of data with excluded missing
      values and data with imputed values, we found that any imputation strategy is
      preferable to the entire exclusion of data. The study also showed that the choice
      of the applied imputation algorithm impacts the resulting networks only
      marginally.

PMID- 30240805
TI  - Correlating new directional measures of myelin and axonal integrity in T2
      weighted MRI with quantitative histology in multiple sclerosis.
AB  - BACKGROUND: Imaging measurement of structure alignment has shown increasing
      importance in determining tissue properties. It is not known if a similar ability
      for characterizing neuropathology exists. NEW METHODS: This study aimed to
      validate a new alignment-assessing method for measuring myelin and axonal
      properties using quantitative histological metrics. The new method involved
      analysis of the Fourier transform (FT) power spectrum in standard magnetic
      resonance imaging (MRI). T2-weighted MRI were collected from 10 post-mortem
      multiple sclerosis (MS) brain samples. Three tissue types were examined: lesions,
      diffusely abnormal white matter, and normal appearing white matter. MRI analysis
      included computing the FT power spectrum; extracting alignment histograms; and
      calculating dominant orientation and alignment complexity (angular entropy). Post
      MRI, the brain samples were processed for myelin and axonal staining, and the
      stained images were used to derive quantitative orientation measures using
      structure tensor analysis for MRI comparison. RESULTS: There were significant
      differences in orientation metrics between tissue types in both MRI and
      histology, and MRI measurements correlated strongly with histological indices.
      Moreover, the joint effect of myelin and axonal entropy explained over 95% of the
      variance of MRI angular entropy. COMPARISON WITH EXISTING METHOD: There is no
      established method for characterizing myelin and axonal pathology using standard
      MRI. Advanced MRI methods have the potential to do this but are still in research
      development and are not yet routinely acquired in clinical practice. CONCLUSIONS:
      Alignment measurement using clinical MRI scans may become a valuable new method
      for characterizing myelin and axonal properties in MS patients.

PMID- 30240806
TI  - Identification and immunogenic evaluation of T cell epitopes based on tembusu
      virus envelope protein in ducks.
AB  - Newly emerging tembusu virus (TMUV) is a severe threat to poultry industry and
      causes huge economic losses. Humoral and cell-mediated immunity are both play
      vital roles in TMUV infection. Up to now, there has been no report on
      identification of T cell epitopes of the TMUV. In this work, we identified T cell
      epitopes within TMUV envelope (E) protein using synthesized peptides predicted in
      silico. A total of ten peptides could stimulate TMUV-specific T cells in murine
      ELISPOT and duck lymphocyte proliferation assay. Subsequently, DNA vaccine
      containing these T cell epitopes was constructed (pVAX-T) and the expression of
      multiepitope protein was confirmed by transfection of BHK-21 cells in vitro.
      Ducks were administrated intramusclarly to evaluated the immunologic effect of
      pVAX-T. In ducks immunized with pVAX-T, antibody against TMUV was undetectable,
      but the expression level of cytokines (IL-2, IL-6, IFN-gamma) was upregulated
      both in peripheral blood lymphocytes and spleen. Furthermore, TMUV challenge
      revealed that cell-mediated immune response sitmulated by pVAX-T contributed to
      protection against TMUV infection. The identification of these T cell epitopes
      will contribute to designing epitope vaccine for preventing infection of TMUV and
      possibly provide the basis for further studies on cell-mediate immune response
      activated by TMUV.

PMID- 30240807
TI  - Genetics, antigenicity and virulence properties of three infectious bronchitis
      viruses isolated from a single tracheal sample in a chicken with respiratory
      problems.
AB  - Three different IBV genotypes/serotypes, designated ck/CH/LDL/150434-I
      (LDL/150434-I), ck/CH/LDL/150434-II (LDL/150434-II) and ck/CH/LDL/150434-III
      (LDL/150434-III), were detected in a single tracheal sample from a chicken
      showing signs of respiratory disease. The viruses were isolated using a cross
      neutralization test and limiting dilution in embryonated specific-pathogen-free
      (SPF) eggs. Isolate LDL/150434-I was a re-isolation of H120 vaccine strain that
      was introduced into the chicken flock by vaccination, transmitted between
      chickens, and later accumulated several genomic mutations. Isolate LDL/150434-II
      was a novel variant that originated from recombination events between H120 and
      ck/CH/LDT3/03-like viruses. The widespread use of H120 vaccine, which offered
      incomplete protection against heterotypic IBVs in the fields, may play important
      roles in the emergence of such a novel genetic variant. Based on the analysis of
      S1 and complete genomic sequence, isolate LDL/150434-III was related genetically
      but distinct from the established strains of nrTW I type viruses of GI-7 lineage
      circulating in Mainland China since 2009. The three IBV isolates were avirulent
      when they infected SPF chickens. Furthermore, synergistic effects on
      pathogenicity were not observed when the different types co-infected the SPF
      chickens. However, the isolates persisted in the respiratory tracts longer in
      combined infected birds than those in individual infected birds. The results
      provide insights into the evolution of the viruses and co-infection of chickens
      with different virus serotypes.

PMID- 30240808
TI  - Voluntary ethanol consumption during early social isolation and responding for
      ethanol in adulthood.
AB  - Little is known about the influence of rearing environments concurrent with
      voluntary intermittent access to ethanol on subsequent adult ethanol-related
      behaviors. Previous research has shown that adult rats reared in post-weaning,
      social isolation conditions (IC) respond more for operant ethanol compared to
      laboratory standard conditions (SC). Ethanol exposed adolescents tend to consume
      more ethanol in adulthood than rats exposed as adults. The current study examined
      voluntary ethanol consumption during adolescence between IC and SC rats,
      subsequent operant responding for ethanol, and extinction of responding in the
      same rats as adults. Differences in ethanol metabolism may alter the amount of
      reward value per unit of ethanol consumed. Therefore, the current study also
      examined Blood Ethanol Concentrations (BEC) between IC and SC rats. Ethanol-naive
      Long-Evans rats arrived in the lab at postnatal day (PND) 21 and were separated
      into either IC or SC where they remained for the duration of the experiments. On
      PND 27, rats received intermittent access to 20% ethanol (3 days/week) for 4 or 6
      weeks. Rats in the 6-week cohort were then trained to lever press for 20% ethanol
      in 30-min sessions followed by extinction. A separate cohort was reared in IC or
      SC, injected with 1.5 or 3.0 g/kg of ethanol (i.p.), followed by BEC measurement.
      Overall, IC rats had higher ethanol preference and consumption during
      adolescence/early-adulthood. IC and SC rats did not differ in their rates of
      operant responding for ethanol and SC rats responded more than IC rats during
      extinction. There were no differences in BEC between IC and SC rats. These
      findings highlight the importance of the environment during rat adolescent
      development with isolation conditions increasing binge-like drinking and ethanol
      preference after 3-4 weeks without differences in metabolism as a potential
      factor. Additionally, the findings indicate that intermittent adolescent access
      to ethanol may change typical differences in operant responding patterns between
      IC and SC rats in adulthood.

PMID- 30240809
TI  - Outcome-specific Pavlovian-to-instrumental transfer (PIT) with alcohol cues and
      its extinction.
AB  - The acquired motivational impact of conditioned stimuli has been studied using
      the Pavlovian-to-instrumental transfer (PIT) task, where a cue paired with a
      reward is consistently shown to energize responses separately trained with that
      same reward ("specific" PIT). However, most alcohol studies have shown that
      alcohol-related cues elevate responses trained with either the same alcohol
      reward or with other non-alcoholic rewards ("general" PIT). The effects of
      extinction on this alcohol PIT effect have not been fully explored. We tested the
      hypothesis that cues signaling different tasting alcohols might acquire specific
      craving reactions for those alcohols leading to specific PIT, but that these
      effects might be sensitive to extinction. Three experiments examined the
      specificity of PIT using alcohol and non-alcohol outcomes. Rats first consumed
      different-flavored alcohol solutions in their home cages. Then they were trained
      to perform two responses, each reinforced with distinctly flavored solutions,
      using a Polycose fading procedure. The outcomes were sweet (4% sucrose) or salty
      (0.9% NaCl) ethanol (10% v/v) solutions (Experiments 1 and 2) or one plain or
      salty alcohol vs a non-alcoholic sweet solution (Experiment 3). Then, two cues
      were each differentially paired with these outcomes. In PIT tests animals
      performed both responses in the presence and absence of these cues without any
      rewards. Experiments 1, 2, and 3 showed that a cue paired with a flavored alcohol
      produced a small but consistent bias towards the response trained with the same
      alcohol solution (specific PIT). Experiment 2 showed that extinction eliminated
      this effect. Experiment 3 demonstrated that specific PIT occurred when
      contrasting salty, or plain, alcohol to a non-alcoholic solution. These results
      provide evidence that alcohol-related stimuli can elicit craving for specific
      types of alcohol (as revealed by specific PIT), but that this effect is sensitive
      to extinction. This paradigm of contrasting two distinctly flavored alcohols may
      be an especially useful animal model of alcohol addiction.

PMID- 30240810
TI  - Subtle changes in host cell density cause a serious error in monitoring of the
      intracellular growth of Chlamydia trachomatis in a low-oxygen environment:
      Proposal for a standardized culture method.
AB  - We monitored Chlamydia trachomatis growth in HeLa cells cultured with either DMEM
      or RPMI medium containing 10% FCS under 2% or 21% O2 conditions for 2 days.
      Bacterial numbers, host cell numbers, and fibrosis-related gene expression in the
      host cells were estimated by an inclusion forming unit assay, a cell counting
      assay, and a PCR array, respectively. In contrast to RPMI, bacterial growth under
      low oxygen conditions in DMEM rapidly decreased with increasing host cell
      density. The addition of supplements (glucose, glutamine, vitamin B12, D-biotin,
      non-essential amino acids, glutathione) to the media had no effect. The growth of
      host cells in DMEM under low oxygen conditions rapidly decreased, although the
      cells remained healthy morphologically. Furthermore, the downregulation of 17
      genes was observed under low oxygen in DMEM. Whereas no effect on bacterial
      growth was observed when culturing in RPMI medium at low oxygen, and the
      downregulation of three genes (CTGF, SERPINE1, JUN) was observed following
      bacterial infection compared with the uninfected control cells. Thus, our
      findings indicate the need for carefully selected culture conditions when
      performing experiments with C. trachomatis under low-oxygen environments, and
      RPMI (rather than DMEM) is recommended when a low host cell density is to be
      used, proposing the major modification of cell culturing method of C. trachomatis
      in a low-oxygen environment.

PMID- 30240811
TI  - Method for isolation of both lactose-fermenting and - non-fermenting Escherichia
      albertii strains from stool samples.
AB  - Initially, Escherichia albertii has been described as a non-lactose fermenting
      bacterium and methods used to isolate it were first based on this phenotypic
      property. However, a recent study showed a variable lactose fermentation
      phenotype for E. albertii suggesting that this microorganism could have been
      underestimated by previous studies using isolation methods based on lactose
      fermentation. In this study, we present a method for the isolation and
      identification of both lactose fermenting and non-fermenting-E. albertii cells in
      stool samples, said method combining culture and isolation on mEA agar, an indole
      test, as well as an E. albertii-specific PCR assay for formal species
      identification. The ability of the procedure to detect E. albertii strains was
      verified using 19 E. albertii strains and 132 non-E. albertii strains
      representing 88 species of different origins majoritary belonging to the
      Enterobacteriaceae family. All indole-positive white colonies grown on mEA agar
      were subjected to E. albertii-specific PCR amplification; all E. albertii strains
      tested were detected with this assay and none of the non-E. albertii strains
      tested was detected. To demonstrate the ability of the procedure to directly
      detect E. albertii in stool samples, E. albertii-inoculated stools were tested
      and for all inoculated samples, E. albertii colonies were easily detected and
      identified. The present study provides a method enable to recover both lactose
      fermenting and -non-fermenting E. albertii strains from clinical samples. This
      method could help to provide a better portrait of the prevalence and
      pathogenicity of E. albertii in clinical samples.

PMID- 30240812
TI  - Novel sensor platform for rapid detection and quantification of coliforms on food
      contact surfaces.
AB  - In this paper, a novel sensor platform based on screen printed carbon electrode
      coated by graphene modified polyacrylamide gel (GR/PAAGC) was developed and
      implemented for sampling, detection and enumeration of coliform bacteria
      (coliforms) on food contact surfaces. The optimized formula of polyacrylamide
      (PAA) and agar-agar increased the adhesive properties of the gel, being crucial
      for the coliforms recovery, attached to food contact surfaces. The 6-Chloro-3
      indoxyl-beta-D-galactopyranoside (6-CIGP) was used as a new electrochemical
      reporter for beta-D-galactosidase activity. The released 6,6'-Dichloro-Indigo (6
      DI) was directly detected by GR/PAAGC sensor. The presence of Isopropyl-beta-D
      thiogalactopyranoside (IPTG) and n-Octyl-beta-D-thiogalactopyranoside (OBDG) in
      the gel contributed to reduction of the detection time. The addition of graphene
      enhanced the voltammetric signal and increased the conductivity of PAA gel. The
      anodic and cathodic peaks of the released product were directly proportional to
      the concentration of coliforms. Bacterial cell concentrations ranging from
      1.6log10CFU/mL to 6.6log10CFU/mL were detected. Well-shaped, sharp voltammetric
      curves were generated within 3 h. Redox peaks exhibited good sensitivity with
      detection limits (LOD) < 0.6log10CFU/mL. After series of optimization
      experiments, coliforms ranging from 0.6log10CFU/cm2 to 6.610CFU/cm2 on stainless
      steel surfaces have been detected within 30 min with a LOD of 0.1log10CFU/cm2.
      The developed rapid, sensitive, reproducible and specific sensor successfully
      applied for single detection as well as for real-time monitoring of growth of
      coliform bacteria on stainless steel surfaces during food processing.

PMID- 30240813
TI  - Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare
      workers.
AB  - An effective post-exposure prophylaxis (PEP) strategy may limit the spread of
      infection. However, there is no consensus regarding PEP for Middle East
      respiratory syndrome coronavirus (MERS-CoV) infection. This study assessed the
      efficacy of ribavirin and lopinavir/ritonavir as PEP for healthcare workers
      (HCWs) exposed to patients with severe MERS-CoV pre-isolation pneumonia. The
      safety of the PEP regimen was assessed. HCWs with high-risk exposure to MERS-CoV
      pre-isolation pneumonia were retrospectively enrolled. HCWs who received PEP
      therapy were classified into the PEP group. PEP therapy was associated with a 40%
      decrease in the risk of infection. There were no severe adverse events during PEP
      therapy.

PMID- 30240814
TI  - Clostridium difficile-related hospitalizations and risk factors for in-hospital
      mortality in Spain between 2001 and 2015.
AB  - AIMS: To examine trends in the incidence, characteristics and in-hospital
      outcomes of Clostridium difficile infection (CDI) hospitalizations from 2001 to
      2015, to compare clinical variables among patients according to the diagnosis
      position (primary or secondary) of CDI, and to identify factors associated with
      in-hospital mortality (IHM). METHODS: A retrospective study was performed using
      the Spanish National Hospital Discharge Database, 2001-2015. The study population
      included patients who had CDI as the primary or secondary diagnosis in their
      discharge report. Annual hospitalization rates were calculated and trends were
      assessed using Poisson regression models and Jointpoint analysis. Multi-variate
      logistic regression models were performed to identify variables associated with
      IHM. FINDINGS: In total, 49,347 hospital discharges were identified (52.31%
      females, 33.69% with CDI as the primary diagnosis). The rate of hospitalization
      increased from 3.9 cases per 100,000 inhabitants in 2001-2003 to 12.97 cases per
      100,000 inhabitants in 2013-2015. Severity of CDI and mean cost per patient
      increased from 6.36% and 3750.11? to 11.19% and 4340.91?, respectively, while IHM
      decreased from 12.66% to 10.66%. Age, Charlson Comorbidity Index, severity,
      length of hospital stay and mean cost were significantly higher in patients with
      a primary diagnosis of CDI. Irrespective of the CDI diagnosis position, IHM was
      associated with male sex, older age, comorbidities, readmission and severity of
      CDI. Primary diagnosis of CDI was associated with lower IHM (odds ratio 0.60; 95%
      confidence interval 0.56-0.65). CONCLUSION: CDI-related hospitalization rates are
      increasing, leading to a high cost burden, although IHM has decreased in recent
      years. Factors associated with IHM should be considered in strategies for the
      prevention and management of CDI.

PMID- 30240815
TI  - Whole genome sequencing reveals a prolonged and spatially spread nosocomial
      outbreak of Panton-Valentine leucocidin-positive meticillin-resistant
      Staphylococcus aureus (USA300).
AB  - BACKGROUND: Whole genome sequencing (WGS) helps to better investigate the
      transmission and characterization of meticillin-resistant Staphylococcus aureus
      (MRSA) strains. AIM: We describe the detection and unfolding of a prolonged and
      spatially distributed nosocomial outbreak of Panton-Valentine leucocidin (PVL)
      positive MRSA ST8 (USA300). METHODS: The outbreak was detected by the combination
      of whole genome sequence (WGS)-based typing, which is implemented for routine
      surveillance of multidrug-resistant bacteria in our institution, and in-depth
      epidemiological investigation. To investigate the source, processes were observed
      and environmental sampling performed. To contain the outbreak, regular and direct
      personal contact with the healthcare workers (HCWs) was maintained and staff
      education implemented. FINDINGS: The outbreak took place between October 2016 and
      November 2017 and included five patients who were treated in two different
      departments as inpatients and outpatients; three were infected, two were
      colonized. Additionally, three HCWs carried the outbreak strain. The strain was
      not found in the hospital environment. Only through non-mediated communication
      did the source become apparent. Decolonization of HCWs and infection control
      measures led to a resolution of the outbreak. CONCLUSION: WGS helped to reveal an
      outbreak that otherwise might have stayed undetected. Nonetheless,
      epidemiological investigation is needed to trace the nosocomial transmission. The
      importance of personal communication in infection control cannot be overstated.

PMID- 30240816
TI  - Molecular cloning of porcine 2',5'-oligoadenylate synthetase-like protein and its
      role in porcine reproductive and respiratory syndrome virus infection.
AB  - Porcine 2',5'-oligoadenylate synthetase-like protein is an essential antiviral
      protein induced by interferons; however, its bioinformatics, genetic
      characteristics and immunological characteristics related to porcine reproductive
      and respiratory syndrome virus are still unknown. In this study, porcine 2',5'
      oligoadenylate synthetase-like protein was cloned, and various attributes were
      predicted by bioinformatics analysis. Through RNAi depletion and overexpression
      methods, it was determined that porcine OASL not only inhibits porcine
      reproductive and respiratory virus replication but also activates interferon-beta
      production and the interferon-beta promoter, promoting the expression of
      interferon-beta mRNA. Through the depletion of different amino acids at the N and
      C termini, the antiviral activity and promoting the activity of interferon beta
      were evaluated. The results demonstrated that 31-60 amino acids at the N terminus
      were critical for virus replication. This study laid a theoretical foundation for
      exploring the characteristics of the porcine 2',5'-oligoadenylate synthetase-like
      protein and suggested a new strategy for the prevention and control of porcine
      reproductive and respiratory syndrome virus and investigation of the therapeutic
      mechanism of this protein.

PMID- 30240817
TI  - Emerging Candida species isolated from renal transplant recipients: Species
      distribution and susceptibility profiles.
AB  - Candidiasis is a major challenge among renal transplant recipients (RTRs)
      worldwide and is associated with high morbidity and mortality rates. Fluconazole
      is the most commonly used agent for Candida infections. However, frequent relapse
      and treatment failure are still reported among patients affected with this
      infection. In the present study, Candida species obtained from RTRs were
      characterized based on conventional and molecular assays. Furthermore, the
      antifungal susceptibility profiles of these species were determined. This study
      was conducted on a total of 126 RTRs within 2012-2016. The patients were
      categorized according to the referenced diagnostic criteria. The identification
      of Candida species was accomplished based on conventional examination,
      assimilation profile test, and polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method. The minimum inhibitory concentrations
      (MICs) of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole,
      and caspofungin were determined based on the guidelines of Clinical and
      Laboratory Standards Institute. The patients with Candida infection were
      diagnosed with urinary tract candidiasis (n = 17), peritonitis (n = 8), intra
      abdominal candidiasis (n = 6), candidemia (n = 4), hepatosplenic candidiasis (n =
      3), and Candida pneumonia (n = 3). A total of 41 Candida isolates, including C.
      albicans (n = 18), C. famata (n = 8), C. kefyr (n = 4), C. tropicalis (n = 4), C.
      parapsilosis (n = 3), C. glabrata (n = 2), and C. lusitaniae (n = 2), were
      isolated from 32.5% (41/126) renal transplant recipients. Fluconazole-resistance
      was observed in seven isolates, entailing C. albicans (n = 6) and C. tropicalis
      (n = 1). Fluconazole MIC for C. lusitaniae isolates was above the epidemiologic
      cut-off value (4-16 MUg/ml). Furthermore, MIC range values of fluconazole against
      C. famata and C. kefyr were obtained as 4-32 MUg/ml and 4-8 MUg/ml, respectively.
      Posaconazole exhibited potent activity against Candida isolates, followed by
      caspofungin. The identification of Candida species, together with susceptibility
      testing, provides important data about the geographic trends of the fluconazole
      resistance profiles of Candida species. It is necessary to maintain a consistent
      method for the implementation of early diagnosis and adoption of treatment
      regimen.

PMID- 30240818
TI  - In-Vitro cytotoxicity, antibacterial, and UV protection properties of the
      biosynthesized Zinc oxide nanoparticles for medical textile applications.
AB  - Nowadays, medical textiles have become the most essential and developing part in
      human healthcare sector. This work was undertaken with a view to harness the bio
      active macromolecules secreted by fungi e.g. proteins and enzymes in bio
      synthesis of ZnO nanoparticles for multifunctional textiles such as antibacterial
      activity and UV protection with considering the cytotoxicity limitation. Herein,
      the isolated fungus, Aspergillus terreus, was allowed to produce proteins which
      has affinity to cape ZnO-NPs. Various factors affecting the behavior of the
      secreted proteins on the formed nanoparticles were investigated. Thorough
      characterizations of the protein capped ZnO-NPs were performed by the using of UV
      Visible spectroscopy, transmission electron microscope (TEM) Fourier Transform
      Infra Red (FT-IR) spectroscopy, X-ray diffraction (XRD) analysis and Dynamic
      light scattering analysis (DLS). Prior treatment of cotton fabrics with ZnO-NPs,
      the cytotoxicity of the protein capped ZnO-NPs was examined. After that, the
      antibacterial activity of the ZnO-NPs before and after treating of cotton
      fabrics, besides, the UV-protection (UPF) properties were investigated. Results
      obviously demonstrated the ability of the bio-secreted protein to cape and reduce
      ZnO to spherical ZnO-NPs with particle size lied around 10-45 nm, as indicated
      form UV-vis., spectra TEM, Zeta sizer, FTIR and XRD. Regarding to the results of
      cytotoxicity, the treatment of the cotton fabrics with ZnO-NPs were performed at
      safe dose (20 ppm). At this dose, ZnO-NPs loaded samples exhibited reasonable
      antibacterial activity against both Gram positive and Gram negative bacteria;
      besides, good UV-protection with reasonable increase in UVA and UVB blocking
      values. Indeed, nanotechnology based microbiological active molecules opens up
      new opportunities for us to explore novel applications in terms of green
      technology.

PMID- 30240819
TI  - Construction and rescue of Muscovy duck-origin goose parvovirus from an
      infectious clone containing an E-box deletion within the left terminal region.
AB  - To obtain a deletion mutant of Muscovy duck-origin goose parvovirus (MDGPV) and
      to analyze its biological characteristics, the pMDGPVPT plasmid, which contains a
      full-length DNA infectious clone of the MDGPV PT strain, was used in this study
      as the template. The E-box at nt 315 of the left inverted terminal repeat
      sequence (L-ITR) was deleted by overlap extension PCR to obtain the infectious
      recombinant plasmid p-PTDeltaE315. The p-PTDeltaE315 plasmid was transfected into
      9-day-old non-immune Muscovy duck embryos via the yolk sac and the rescued
      deletion mutant virus r-PTDeltaE315 was generated. Experiments to demonstrate the
      novel deletion mutant virus' biological characteristics showed that r-PTDeltaE315
      can cause typical lesions after infection of Muscovy duck embryos. Compared with
      its parent strain PT, the virulence of r-PTDeltaE315 and its proliferation
      ability in Muscovy duck embryos were attenuated, but its ability to replicate in
      MDEF cells was enhanced. This study laid the foundation for further understanding
      of the relationship between E-box deletion in the L-ITR and MDGPV virulence.

PMID- 30240820
TI  - A combined mathematical model linking the formation of amorphous solid
      dispersions with hot-melt-extrusion process parameters.
AB  - Hot-melt extrusion allows for the continuous production of amorphous solid
      dispersions, which are used to enhance bioavailability of poorly soluble drugs in
      pharmaceutical drug delivery. To facilitate formulation and extrusion process
      development, we propose a mathematical model describing the formation of
      amorphous solid dispersions in the context of this process. The model is based on
      the calculation of two key process values: (1) time to dissolution of solid drug
      particles in molten polymer during extrusion and (2) mean residence of material
      in the extruder. We suggest that their linking allows for rational process
      design. Experimental data support the validity of our model for both key process
      values as well as the overall process. This modeling approach allows for fast and
      cost-effective formulation and extrusion process development as well as
      feasibility estimations in early stages of drug development.

PMID- 30240821
TI  - Mitochondrial regulation by pyrroloquinoline quinone prevents rotenone-induced
      neurotoxicity in Parkinson's disease models.
AB  - Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory
      chain, has been reported to protect SH-SY5Y cells from cytotoxicity induced by
      rotenone, a mitochondrial complex I inhibitor. In this study, we aimed to
      investigate the mitochondrial mechanisms involved in the neuroprotection of PQQ
      both in vitro and in vivo. The cultured human SH-SY5Y neuroblastoma cells were
      exposed to different concentrations of PQQ after which the cells were treated
      with rotenone. Electron microscopy images showed that PQQ could prevent the
      mitochondrial morphology damage. The down-regulation of mitochondrial biogenesis
      related genes (PGC-1alpha and TFAM) and mitochondrial fission and fusion related
      genes (Drp1and Mfn2) in rotenone-injured SH-SY5Y cells could be inhibited by PQQ.
      PQQ could also promote the transposition of Drp1 and Mfn2 from cytosol to
      mitochondria. In addition, rotenone was injected into the left medial forebrain
      bundle of SD rats to establish a Parkinson's disease (PD) model in vivo, after
      which different doses of PQQ or Edaravone were given intraperitoneally once daily
      for 8 weeks. PQQ could up-regulate the mRNA levels of PGC-1alpha, TFAM, Drp-1 and
      Mfn2 in the midbrain of PD rats. Our findings indicated that PQQ could prevent
      mitochondrial dysfunction by promoting mitochondrial biogenesis and regulating
      mitochondrial fission and fusion, which might contribute to its neuroprotective
      effect in PD models.

PMID- 30240822
TI  - Association between function and structure of the triple network and catechol-O
      methyltransferase val158met polymorphism in the first episode schizophrenia.
AB  - The aberrant orchestration between the triple networks has been suggested as a
      backbone for some cognitive and clinical features of schizophrenia. The salience
      network (SN) plays a general role in switching between the central executive
      network (CEN) and the default mode network (DMN) mediated by dopamine activity.
      Whether the disease state and dopamine associated gene, catechol-O
      methyltransferase (COMT), has an interactive effect on the function and structure
      of the triple network has not been understood. To this end, independent component
      analysis was used to identify the triple network. Then, cortical thickness and
      inter-regional resting state functional connectivity (RSFC) of the triple network
      was investigated in 55 first episode schizophrenia (FES) patients and 53 age-,
      gender-, and education- matched healthy controls. Finally, we investigated if
      there exist interactive effect between disease and COMT gene variation on the
      abnormal brain structure and function. Our results show that patients with FES
      exhibited significantly increased RSFC between anterior cingulate cortex and left
      dorsolateral prefrontal cortex (DLPFC) compared with healthy controls. The
      cortical thickness of the left DLPFC was thinner in FES patients. Significant
      interaction effect between COMT and disease was found in cortical thickness of
      the left DLPFC. Specifically, cortical thinning in this region was evident with
      the val homozygotes group of the COMT gene in FES. This findings suggest abnormal
      RSFC between CEN and SN and thinker cortical thickness in FES. And the val
      homozygotes of COMT may contribute to further cortical thinning in FES patients.

PMID- 30240823
TI  - Sex differences in the effects of adult short-term isolation rearing on
      contextual fear memory and extinction.
AB  - Fear conditioning and extinction is a useful tool for understanding the
      pathogenesis of fear-related disorders including post-traumatic stress disorder
      (PTSD) and for developing treatments for them. To investigate the role of sub
      brain regions or molecular mechanisms in fear conditioning and extinction,
      neuroscientists have been employing an optogenetic or in vivo recording
      technique, in which placement of an optical fiber or an electrode into the brain
      region of a free-moving mouse is essential. These methods require isolation
      rearing (at least one week) from the brain surgery to the behavioral test.
      Although such short-term adult rearing has been shown not to influence fear
      memory and extinction in males, the effect in females remains unclear. In the
      present study, we investigated the effect on fear memory and fear extinction of
      adult isolation rearing during the one week before contextual fear conditioning
      in both male and female mice. This short-term adult isolation rearing increased
      fear responses in the contextual fear memory test in females but not in males. On
      the other hand, the rearing showed no effect on fear responses during fear
      extinction or the recall test in either sex. In summary, adult short-term
      isolation rearing enhanced only fear memory, and only in females.

PMID- 30240824
TI  - Protective effect of dioscin against intestinal ischemia/reperfusion injury via
      adjusting miR-351-5p-mediated oxidative stress.
AB  - Oxidative stress plays important roles in intestinal ischemia-reperfusion (II/R)
      injury, and exploration of effective lead compounds against II/R injury via
      regulating oxidative stress is necessary. In this study, the effects and possible
      mechanisms of dioscin against hypoxia-reoxygenation (H/R) injury in IEC-6 cells
      and II/R injury in mice were investigated. The results showed that dioscin
      markedly increased cell viability, and reduced ROS level caused by H/R injury in
      IEC-6 cells. in vivo, dioscin significantly reduced the levels of MDA, MPO and
      chiu' score, increased SOD level, and improved pathological changes caused by
      II/R injury in mice. Mechanism investigation showed that dioscin markedly up
      regulated the expression levels of Sirt6 by decreasing miR-351-5p levels,
      decreased the expression levels of p-FoxO3alpha via activating AMPK, and
      increased the expression levels of MnSOD and CAT. In addition, miR-351-5p mimic
      in IEC-6 cells and agomir in mice increased ROS levels and aggravated II/R
      injury. MiR-351-5p inhibitor in IEC-6 cells and antagomir in mice alleviated
      these actions by adjusting Sirt6 signal pathway. MiR-351-5p interference
      experiment further confirmed that dioscin increased Sirt6 expression level by
      down- regulating miR-351-5p level to inhibit oxidative stress and reduce II/R
      injury. Furthermore, we also demonstrated that dioscin inhibited the expression
      level of miR-351-5p via reducing TRBP expression level during the generation of
      miR-351-5p mature body. Dioscin showed protective effect against II/R injury via
      adjusting miR- 351-5/Sirt6 signal to reduce oxidative stress, which should be
      considered as one potent candidate to treat II/R injury. In addition, miR-351
      5/Sirt6 could be one effective drug target against II/R injury.

PMID- 30240825
TI  - Understanding netrins and semaphorins in mature endothelial cell biology.
AB  - Netrins and semaphorins are known as neuronal guidance molecules that are
      important to the facilitate patterning of the nervous system in embryonic
      development. In recent years, their function has been broadened to guide
      development in other systems, including the vascular system, where netrins and
      semaphorins critically contribute to the development of the vascular system.
      Evidence is accumulating that these guidance cues are also of critical importance
      in the biology of the mature endothelium by regulating the maintenance of
      endothelial quiescence. Here we review our current insights into the roles of
      netrins and semaphorins in endothelial cell survival, self-renewing, barrier
      function, response to wall shear stress, and control of the vascular tone. We
      also provide suggestions for future research into the functions of netrins and
      semaphorins in mature endothelial cell biology.

PMID- 30240826
TI  - Unmodified hydrated S60 fullerene molecules exhibit antioxidant properties,
      prevent damage to DNA and proteins induced by reactive oxygen species and protect
      mice against injuries caused by radiation-induced oxidative stress.
AB  - Unmodified hydrated S60 fullerene molecules (C60UHFM) were shown to reduce the
      formation ROS in water and 8-oxoguanine in DNA upon ionizing radiation impact.
      C60UHFM efficiently eliminate long-lived protein radicals arising after
      irradiation. In irradiated mice C60UHFM reduce the rate of single/double-strand
      DNA breaks and amount of chromosomal breaks. The radioprotective activity of
      C60UHFM was estimated by the survival rate of animals; the dose modification
      factor for animal survival was 1.3. Hematological tests showed that C60UHFM
      injection in mice prior to irradiation results in a decrement of irradiation
      induced leucopenia and thrombocytopenia. Histological analysis testified that
      C60UHFM provide significant protection of small intestine tissues in mice against
      irradiation-induced damage. The obtained data assume that the radioprotective
      properties of C60UHFM are determined by their antioxidant, antiradical and DNA
      protective qualities. Thus, it was demonstrated that C60UHFM are a novel
      antioxidant and radioprotective agent capable of substantial reduction of the
      harmful effects of ionizing radiation.

PMID- 30240827
TI  - 2D materials for next generation healthcare applications.
AB  - 2 dimensional (2D) materials are budding new class of materials with exciting
      potential in optical, electrical, chemical and biomedical applications. Inspired
      by the attractive properties of graphene attributing to its 2D structure has
      stimulated researchers to hunt for new 2D materials. Unique characteristics like
      high surface-volume ratio, shape, surface charge, anisotropic nature and tunable
      functionalities of 2D structures opens up its application scope further. 2D
      materials have marked their impact on a wide range of area notably material
      science, optoelectronics, engineering and biomedical science. Currently,
      researchers are focusing on developing new 2D materials and functionalizing 2D
      materials to achieve desired properties. This review underlines the recent
      renovations done to 2D materials so as improve its functionality and
      biocompatibility. Growing trend towards exploring the potential of 2D materials
      for biomedical applications including targeted drug delivery, imaging,
      photothermal therapy, tissue engineering and regenerative medicine emphasize the
      need to consider its biosafety. Large surface area of 2D materials increases
      chances of exposure of these materials towards cells which in turn shoots up the
      possibility for cellular interactions augmenting chances of potential toxicity.
      The present review concludes that the 2D materials are promising choice for next
      generation biomedical device development.

PMID- 30240828
TI  - Nonionic surfactants increase digoxin absorption in Caco-2 and MDCKII MDR1 cells:
      Impact on P-glycoprotein inhibition, barrier function, and repeated cellular
      exposure.
AB  - Nonionic surfactants commonly used in pharmaceutical formulations may have P
      glycoprotein (P-gp) inhibiting and/or permeation enhancing effects. The present
      work aims to distinguish these effects and assess the degree of cellular recovery
      after multiple exposures to nonionic surfactants. The investigated surfactants
      were polysorbates (PS): PS20, PS40, PS60, PS65, PS80 and PS85; monosaccharide
      based: lauroyl methyl glucamide and n-nonyl-beta-D-glucopyranoside; or
      disaccharide-based: lauryl-beta-D-maltoside and trehalose 6-laurate. Bi
      directional permeability studies of digoxin and mannitol, and calcein-AM efflux
      assay were performed in cell cultures. Cellular recovery was evaluated by
      continuous measurements of transepithelial electrical resistance (TEER) in Caco-2
      cell monolayers. Polysorbates with one fatty acid chain decreased the efflux of
      digoxin through P-gp inhibition in MDCKII MDR1 cells. Mono- and di-saccharide
      based surfactants, in a dose dependent manner, enhanced digoxin absorptive
      permeability without decreasing the secretory permeability in Caco-2 cells,
      suggesting that the surfactants had a transcellular permeation enhancing effect.
      Caco-2 cell monolayers recovered to different degrees of 60-100% of the initial
      TEER values. Calcein-AM assay was found to be non-predictive to surfactants
      influence on digoxin permeability across cell monolayers. In conclusion, these
      results may assist, in a mechanism-based, selection of suitable surfactants for
      formulating oral dosage forms to enhance the absorption of low bioavailable P-gp
      substrates.

PMID- 30240829
TI  - Assessment of HBEC-5i endothelial cell line cultivated in astrocyte conditioned
      medium as a human blood-brain barrier model for ABC drug transport studies.
AB  - Endothelial cells are main components of the Blood-Brain Barrier (BBB) and form a
      tight monolayer that regulates the passage of molecules, with the ATP-Binding
      Cassette (ABC) transporters efflux pumps. We have developed a human in vitro
      model of HBEC-5i endothelial cells cultivated alone or with human astrocytes
      conditioned medium on insert. HBEC-5i cells showed a tight monolayer within 14
      days, expressing ZO-1 and claudin 5, a low apparent permeability to small
      molecules, with a TEER stability during five days. The P-gp, BCRP, MRPs
      transporters were well expressed and functional. Accumulation and efflux ratio
      measurement with different ABC transporters substrates (Rhodamine 123, BCECF AM,
      Hoechst 33342) and inhibitors (verapamil, Ko143, probenecid and cyclosporin A)
      were conducted. At barrier level, the functionality of ABC transporters was three
      fold enhanced in astrocyte conditioned medium. We validated our model by the
      transport of pharmacological substrates: caffeine, rivaroxaban, and methotrexate.
      The rivaroxaban and methotrexate were released with an efflux ratio >3 and were
      decreased by more than half with inhibitors. HBEC-5i model could be used as
      relevant tool in preclinical studies for assessing the permeability of
      therapeutic molecules to cross human BBB.

PMID- 30240830
TI  - A hypothesis-driven weight-of-evidence analysis to evaluate potential endocrine
      activity of perfluorohexanoic acid.
AB  - Perfluorohexanoic acid (PFHxA) is a potential impurity and environmental
      degradation product of C6-based fluorotelomer products. Considering the potential
      endocrine activity of perfluoroalkyl acids, a hypothesis-driven weight-of
      evidence (WoE) analysis was conducted to evaluate the potential endocrine
      disruptor activity of PFHxA, as defined by World Health Organization (WHO),
      across estrogen (E), androgen (A), thyroid (T), and steroidogenesis (S) pathways.
      A comprehensive literature search identified primary and secondary studies across
      species for review. The ToxCast/Tox21 database provided in vitro data. Studies
      identified were reviewed for reliability, and relevance, with endocrine endpoints
      ranked, and lines of evidence evaluated across pathways. Overall, PFHxA showed no
      endocrine effects in Japanese medaka, juvenile rainbow trout, chickens or
      reproductive parameters in northern bobwhite with no significant activity in
      rodent repeated-dose toxicity, lifetime cancer, or reproductive and developmental
      studies. In vitro, there was weak or negative activity for T transport protein or
      activation of E, A or T receptors. PFHxA was also negative in vitro and in vivo
      for disrupting steroidogenesis. Based on this WoE endocrine analysis, PFHxA
      exposure did not cause adverse effects associated with alterations in endocrine
      activity in these models, as such would not be characterized as an endocrine
      disruptor according to the WHO definition.

PMID- 30240831
TI  - Toxicological safety evaluation of 3,3'-diselenodipropionic acid (DSePA), a
      pharmacologically important derivative of selenocystine.
AB  - Diselenodipropionic acid (DSePA), a pharmacologically important derivative of
      selenocystine was evaluated for acute toxicity, mutagenic safety and metabolic
      stability. The estimated median oral lethal dose (LD50) cut-off of DSePA in mice
      and rat models was ~200 mg/kg and ~25 mg/kg respectively, which is considerably
      higher than the reported oral LD50 dose of its parent compound. Subsequently
      DSePA treatment in absence and presence of rat liver S9 fraction was found to be
      non-mutagenic at the tested doses up to 1 mM in rifampicin resistance assay and
      up to 6 mM in Ames test. In vitro degradation studies indicated that DSePA was
      more stable in S9 fraction of human compared to rat. The kinetic parameters Km
      and Vmax of DSePA degradation estimated using rat S9 fraction was 9.81 MUM and
      1.06 nmol/ml/min respectively. Further, DSePA treatment (1-50 MUM) with or
      without rat S9 fraction did not induce any toxicity in human intestinal
      epithelial cells (Int 407) while showing comparable bioactivity of glutathione
      peroxidase (GPx) level. In conclusion, superior metabolic stability of DSePA in
      human S9 fraction with a concomitant lack of mutagenic effects suggests that it
      may be a suitable derivative of selenocytine for future biological studies.

PMID- 30240832
TI  - Allergic contact dermatitis: Adequacy of the default 10X assessment factor for
      human variability to protect infants and children.
AB  - When evaluating consumer products for safety, one must consider the heterogeneity
      of the population that might use those products, including the potential for
      different sensitivity based on factors such as age, gender, and genetics. For
      both systemic endpoints and allergic contact dermatitis (ACD), quantitative
      safety evaluations typically include a default 10-fold uncertainty/assessment
      factor to account for inter-individual variability. While this factor is intended
      to include age, the adequacy of the default 10-fold factor has been questioned
      for infants, for whom a precautionary assumption is often made that they are more
      sensitive. In-depth evaluations of the adequacy of the 10-fold factor have been
      published for systemic endpoints, but relatively little has been published to
      substantiate this for ACD. This paper reviews the state of the science regarding
      the etiology of ACD and factors that suggest an overall decreased sensitivity
      associated with early life exposures, thus confirming the sufficiency of the 10
      fold inter-individual factor to provide protection for children and infants.
      While it remains prudent for all age groups to avoid contact with sensitizers, it
      is concluded that the quantitative methods used in safety evaluation to prevent
      the induction of skin sensitization are protective for infants, including
      neonates and premature infants.

PMID- 30240833
TI  - Genetic variability of Panstrongylus geniculatus (Reduviidae: Triatominae) in the
      Metropolitan District of Caracas, Venezuela.
AB  - Panstrongylus geniculatus has become the most frequently registered vector of
      Chagas disease in the metropolitan area of Caracas, Venezuela. This triatomine
      species has invaded urban areas in recent years and has been implicated in
      multiple oral outbreaks of Chagas disease in the region. The study of genetic
      variability and spatial structure in P. geniculatus populations can provide
      information about possible events of domiciliation and aid intervention programs
      against triatomine species rapidly adapting to urban ecotopes. We sequenced a
      region of the cytochrome-b gene in 114 specimens of P. geniculatus from the
      Metropolitan District of Caracas and assessed patterns of gene flow and
      phylogenetic relationships among these individuals. A total of 29 haplotypes were
      detected in the two sampled municipalities, Sucre and Libertador. Though high
      genetic connectivity was observed between the municipalities (FST = 0.10796; Nm =
      11.20), subtle genetic structuring was also observed in particular geographic sub
      regions. Based on neutrality tests and the observed allele-frequency
      distribution, the Panstrongylus geniculatus population appears to be expanding
      and adapting to different microhabitats present in the study area. Our findings
      affirm the capacity of this insect to adapt to different environments and
      emphasize its principal role in the epidemiology of Chagas disease in northern
      Venezuela.

PMID- 30240834
TI  - Genome-wide analysis of Borrelia turcica and 'Candidatus Borrelia tachyglossi'
      shows relapsing fever-like genomes with unique genomic links to Lyme disease
      Borrelia.
AB  - Borrelia are tick-borne bacteria that in humans are the aetiological agents of
      Lyme disease and relapsing fever. Here we present the first genomes of B. turcica
      and B. tachyglossi, members of a recently described and rapidly expanding
      Borrelia clade associated with reptile (B. turcica) or echidna (B. tachyglossi)
      hosts, transmitted by hard ticks, and of unknown pathogenicity. Borrelia
      tachyglossi and B. turcica genomes are similar to those of relapsing fever
      Borrelia species, containing a linear ~ 900 kb chromosome, a single long (> 70
      kb) linear plasmid, and numerous short (< 40 kb) linear and circular plasmids, as
      well as a suite of housekeeping and macronutrient biosynthesis genes which are
      not found in Lyme disease Borrelia. Additionally, both B. tachyglossi and B.
      turcica contain paralogous vsp and vlp proteins homologous to those used in the
      multiphasic antigen-switching system used by relapsing fever Borrelia to evade
      vertebrate immune responses, although their number was greatly reduced compared
      to human-infectious species. However, B. tachyglossi and B. turcica chromosomes
      also contain numerous genes orthologous to Lyme disease Borrelia-specific genes,
      demonstrating a unique evolutionary, and potentially phenotypic link between
      these groups. Borrelia tachyglossi and B. turcica genomes also have unique
      genetic features, including degraded and deleted tRNA modification genes, and an
      expanded range of macronutrient salvage and biosynthesis genes compared to
      relapsing fever and Lyme disease Borrelia. These genomes and genomic comparisons
      provide an insight into the biology and evolutionary origin of these Borrelia,
      and provide a valuable resource for future work.

PMID- 30240835
TI  - Instantaneous frequency based index to characterize respiratory crackles.
AB  - BACKGROUND: Crackle is a lung sound widely employed by health staff to identify
      respiratory diseases. The two-cycle duration (2CD) is a quantitative index
      pointed out by the American Thoracic Society and the European Respiratory Society
      to classify respiratory crackles as fine or coarse. However, this index, measured
      in the time domain, is highly affected by noise and filters of recording systems.
      Such factors hamper the analysis of data reported by different research groups.
      This work proposes a new index based on the instantaneous frequency of crackles
      estimated by means of discrete-time pseudo Wigner-Ville distribution. METHOD:
      Comparisons between 2CD and the proposed index were carried out for simulated and
      actual crackles. Normal breathing sounds were added to simulated crackles; the
      resulting signals were then applied to a band-pass filter that mimics those
      belonging to lung sound acquisition systems. Thus, the impact of noise and
      filtering on these two indices was assessed for simulated crackles. Kruskal
      Wallis and Dunn's tests as well as Gaussian mixture model (GMM) were applied to
      the two indices measured from 382 actual crackles belonging to open databases.
      RESULTS: The proposed index is much less susceptible to waveform distortions due
      to noise and filtering when compared to the 2CD. Thus, the statistical analyses
      allow the identification of two classes of crackles from actual databases; the
      same does not occur when using 2CD. CONCLUSIONS: The new proposed index has the
      potential to contribute for a better characterization of crackles generated by
      different respiratory diseases, assisting their diagnosis during clinical exams.

PMID- 30240836
TI  - An update on Staphylococcus aureus infective endocarditis from the International
      Society of Antimicrobial Chemotherapy (ISAC).

PMID- 30240837
TI  - Antimicrobial susceptibility of non-fermenting Gram-negative pathogens isolated
      from cystic fibrosis patients.
AB  - Non-fermenting Gram negative bacteria are increasingly being cultured in
      respiratory samples from people with cystic fibrosis (CF). This study aimed to
      determine the susceptibility of clinical CF respiratory isolates from distinct
      geographical regions to a range of antimicrobials. A total of 286 isolates (106
      Stenotrophomonas maltophilia, 100 Burkholderia spp., 59 Achromobacter spp., 12
      Pandoraea spp. and 9 Ralstonia spp.) from The Netherlands, Northern Ireland,
      Spain, USA and Australia were tested. The MIC50, MIC90 and susceptibility
      categorization were determined. Cotrimoxazole was the most active compound for
      all the microorganisms (MIC50=0.12-4 mg/L, MIC90=1-16 mg/L). For S. maltophilia,
      47% and 62% of isolates were susceptible to cotrimoxazole according to CLSI and
      EUCAST breakpoints, respectively. Ceftazidime presented a lower level of
      susceptibility (35%, MIC50=32 mg/L, MIC90=256 mg/L). Tobramycin and colistin
      MIC90 were >128 mg/L and >16 mg/L, respectively. Regarding Burkholderia isolates,
      72%, 56% and 44% were susceptible to cotrimoxazole, ceftazidime and meropenem,
      respectively. For both ceftazidime and meropenem, the MIC50 and MIC90 values were
      within the intermediate or resistant category. The most active antibiotics for A.
      xylosoxidans were cotrimoxazole (MIC50=2, MIC90=8 mg/L) and imipenem (MIC50=2,
      MIC90=8 mg/L). Cotrimoxazole, imipenem, and ciprofloxacin were active against the
      12 Pandoraea species (MIC50= 0.12-4 mg/L, MIC90= 1-8 mg/L). Ciprofloxacin
      (MIC50=4 mg/L) and cotrimoxazole (MIC50=1 mg/L) were the only active antibiotics
      for Ralstonia spp. There were no statistically significant differences in
      susceptibility rates between countries. Non-fermenting Gram-negative bacteria
      other than P. aeruginosa are potential pathogens in CF and cotrimoxazole has
      demonstrated to be the most active compound against them.

PMID- 30240838
TI  - An alternative strategy for combination therapy: Interactions between polymyxin B
      and non-antibiotics.
AB  - Antimicrobial resistance is increasing and few new antibiotics are in the
      development pipeline. Alternative strategies to treat infectious diseases, such
      as combination therapy, are urgently needed. Polymyxin B is a neglected and
      disused antibiotic with moderate antibacterial activity. In this study, we aimed
      to find synergistic interactions between polymyxin B and a wide range of non
      antibiotics (non-ABs) to improve its efficacy. Thirty non-AB compounds from
      various drug classes were screened for synergistic potential with sub-minimum
      inhibitory concentrations (MICs) of polymyxin B in an agar diffusion assay
      against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and
      Pseudomonas aeruginosa (3 isolates per species). Potential candidates were
      further studied in in vitro checkerboard assays, up to 5 isolates per species,
      using optical density to assess growth. Interactions were assessed with
      fractional inhibitory concentration index (FICi) analysis and surface response
      analysis with Loewe, Bliss and Highest Single Agent analysis using the Combenefit
      program. Twenty non-ABs enhanced polymyxin B activity in the agar diffusion test
      in one or more species. Of these, three showed a consistent synergistic effect
      (FICi <= 0.5) in the checkerboard assay for at least one species: citalopram,
      sertraline and spironolactone. Surface response analyses were largely in
      concordance, and further assessment showed only spironolactone was synergistic
      with polymyxin B at clinically relevant levels. The screening strategy used
      showed consistent synergism in vitro between polymyxin B and some non-ABs for A.
      baumannii, E. coli and K. pneumoniae. The synergistic interactions found merit
      further exploration as alternative strategies for difficult-to-treat infections.

PMID- 30240839
TI  - Effects of prophage regions in a plasmid carrying a carbapenemase gene on
      survival against antibiotic stress.
AB  - We investigated the evolutionary importance of cryptic prophage elements in a
      blaNDM-1-bearing plasmid by exploring the effect of prophage regions on survival
      against antibiotic stress. While analysing a plasmid harboring an NDM-1-encoding
      gene in Klebsiella pneumoniae from South Korea, we found a prophage region within
      the plasmid. We constructed single-prophage knockout (KO) mutants by gene
      replacement. The intact plasmid and plasmids with deleted prophages were
      conjugated into Escherichia coli DH5alpha. Growth rate and antibiotic
      susceptibility were determined, and survival rates of strains were evaluated in
      the presence of antibiotics, such as imipenem, amikacin, gentamicin, cefotaxime,
      and piperacillin/tazobactam. A transcriptional response of sigma factor-coding
      genes (rpoS and rpoE) and reactive oxygen species (ROS)-related genes from
      different operons (soxS, fumC, oxyR, and katE) to a sub-inhibitory concentration
      of aminoglycosides was monitored by quantitative real-time polymerase chain
      reaction (qRT-PCR). The prophage region consists of four cryptic prophages of
      16,795 bp and 19 coding DNA sequences. An Escherichia coli transconjugant
      carrying the plasmid with intact prophages showed increased survival during
      treatment with various antibiotics, including imipenem and amikacin; however,
      transconjugants carrying this plasmid with a single-prophage KO did not. mRNA
      expression analyses revealed that sigma factor proteins (rpoB and rpoE) were
      highly upregulated by antibiotics. We propose that cryptic prophages in the
      antibiotic resistance plasmid may contribute to adaptation of the bacterial host
      to antibiotic stress. We are concerned that the combination of prophages with a
      drug resistance plasmid helps drug-resistant bacteria in a hostile environment
      and accelerates their dissemination.

PMID- 30240840
TI  - Cognition-related white matter integrity dysfunction in Alzheimer's disease with
      diffusion tensor image.
AB  - Alzheimer's disease (AD) is a worldwide progressive neurodegenerative disorder in
      the elderly. Previous research has indicated that Alzheimer's disease impairs
      white matter (WM) tracts. Anatomical and neuroimaging studies have indicated that
      WM tracts are associated with cognitive function. Whether the abnormal WM
      integrity in AD is associated with cognitive impairments and the clinical
      symptoms is still not clear. To this end, we investigated the relationship
      between the impairments in WM tracts and the decline of cognitive ability in AD.
      Diffusion tensor imaging (DTI) data were collected from 38 AD patients and 30
      normal, cognitively healthy volunteers. The tract-based spatial statistics (TBSS)
      approach was used to compare the fractional anisotropy (FA) and mean diffusivity
      (MD) values between the two groups. WM tracts (cingulum, superior longitudinal
      fasciculus (SLF), uncinate fasciculus (UF), and inferior longitudinal fasciculus
      (ILF)) associated with cognition function were extracted for region of interest
      (ROI)-based analysis. Significantly decreased FA values and increased MD values
      of the cognition-related WM tracts were observed in the AD group compared with
      the normal cognition (NC) group. In addition, we further demonstrated that the
      decreased FA values and increased MD values of the cognition-related WM tracts
      were significantly correlated with MMSE scores. These results indicated that
      abnormal changes in WM integrity are observed following AD. Finally, we used
      support vector machine (SVM) with a repeated, stratified 10-fold cross-validated
      classifier to evaluate the ability of FA and MD values to discriminate disease.
      The accuracy of the SVM using cognition-related WM as classified features was
      higher than that using non-cognition-related tracts. Most importantly, our
      results showed the relationship between abnormal WM tracts and cognitive ability
      in AD. These findings further suggested that AD-related impairments in cognition
      related WM tracts may influence the cognitive ability of AD patients.

PMID- 30240841
TI  - MicroRNA-410 inhibition of the TIMP2-dependent MAPK pathway confers
      neuroprotection against oxidative stress-induced apoptosis after ischemic stroke
      in mice.
AB  - Ischemic stroke (IS) is an acute cerebral event characterized by a high incidence
      rate, high disability rate as well as a high mortality. More recently,
      accumulative literature has provided evidence highlighting the role played by
      microRNAs (miRs) in the development of neurons. Hence, the aim of the present
      study was to investigate the neuroprotective role of miR-410 in IS. Microarray
      based gene expression profiling of AMI was conducted in order to identify
      differentially expressed genes (DEGs) and the corresponding miRs regulating these
      genes. IS models were established to assess neurology on a scoring basis.
      Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity and
      malondialdehyde (MDA) were all subsequently assessed. The functional role of miR
      410 in IS was determined based on ectopic expression, knockdown and reporter
      assay experiments in hippocampal neurons. The expressions of microRNA-410, TIMP2,
      ERK, p38MAPK, JNK were all examined accordingly. The survival rate was assessed
      by MTT assay, and cell cycle and apoptosis by flow cytometry. After the loss of
      hippocampal neurons, infarct size as well as oxidative stress injury had been
      detected, microarray technology revealed that TIMP2 was differentially expressed
      in IS and that miR-410 regulated TIMP2. Initial observations revealed elevated
      levels of TIMP2 expression and MDA activity, in addition to evidence obtained
      indicated that the MAPK pathway had been activated along with decreased SOD, GSH
      Px activity and miR-410 expression in IS mice. Ectopic expression of miR-410 was
      observed to inactivate the MAPK pathway, TIMP2 expression and hippocampal neuron
      apoptosis, while elevated hippocampal neuron survival rates and cell cycle entry
      were detected. Furthermore, TIMP2 as a direct target gene of miR-410, was
      determined to be negatively regulated by miR-410, while the MAPK pathway was
      found to be inhibited following TIMP2 knockdown. Our results revealed that the
      overexpression of miR-410 could ameliorate hippocampal neuron loss, reduce
      infarct size and oxidative stress injury in IS mice. Taken together, the key
      evidence of the current study elucidated the distinct nature of the inhibitory
      effect on IS as a result of overexpressed miR-410 whereby the conferral of
      neuroprotection was observed in oxidative stress-induced apoptosis post IS
      through the TIMP2-dependent repression of the MAPK pathway in mice.

PMID- 30240842
TI  - New inhibitors of matrix metalloproteinases 9 (MMP-9): Lignans from Selaginella
      moellendorffii.
AB  - Matrix metalloproteinase 9 (MMP-9) is one of the structurally related zinc
      dependent endopeptidases families and provides a new target for cancer therapy
      owing to its pivotal role in metastatic tumors. In this paper, fourteen lignans,
      including three novel lignans, named selamoellenin B-D (1-3), and eleven known
      lignan derivatives (4-14) were isolated from the plant of Selaginella
      moellendorffii. Among them, compound 3 is optically active, which was
      enantiomerically seperated to afford a pair of enantiomers, (-)-3 and (+)-3.
      Their structures were elucidated by extensive spectroscopic analyses. Their
      cytotoxic activities were evaluated against four human cancer cell lines. Among
      them, five compounds (4, 5, 6, 11 and 13) exhibited great potent cytotoxicity and
      their structure-activity relationships were also discussed. All compounds except
      for 3 lignan analogues with low cytotoxicity were selected for further in vitro
      enzyme inhibition, surface plasmon resonance (SPR), and molecular docking assays
      based on the MMPs target. The results shown that, compound 11 have the best
      inhibitory effect and can be considered as a potential drug candidate targeting
      at MMP-9 for cancer therapy.

PMID- 30240843
TI  - Phytochemical and antimicrobial study of Pilocarpus pennatifolius Lemaire.
AB  - The investigation of the crude extract of leaves and bark of Pilocarpus
      pennatifolius Lemaire allowed isolated of a not yet described coumarin, together
      with three known coumarins (bergapten, xanthotoxin and dimethyl allyl
      xanthyletin), and a not yet described imidazole alkaloid. All structures were
      established by means of spectral analysis, including extensive 2D NMR studies. In
      addition, the alkaloid had its absolute stereochemistry determined by X-ray
      diffraction. Meanwhile, extracts and pure compounds were tested against various
      strains of bacteria and fungi, showing promising antimicrobial activities. We
      highlight the activities of crude bark methanol extract (CBME), of the leaf basic
      acetate fraction (LBAcF), and of compound 2 against the Gram negative bacteria
      Shigella flexneri (MICs = 7.8, 7.8 and 3.12 MUg.mL-1, respectively), of compound
      5 against the Gram positive Enterococcus fecalis (MIC = 1.56 MUg.mL-1), and
      against two Gram negative bacteria Salmonella enteritidis (MIC = 1.56 MUg.mL-1),
      and Pseudomonas aeruginosa (MIC = 6.25 MUg.ml-1). On the other hand, CBME and
      compounds 3-5 showed excellent activity against the fungus Candida krusei with
      MICs of 15.6, 1.56, and 3.12 MUg.mL-1 respectively, as actives or better than the
      antifungal standard fluconazole (MIC = 3.12 MUg.mL-1).

PMID- 30240844
TI  - Three new phenanthrenes with antimicrobial activities from the aerial parts of
      Juncus effusus.
AB  - Three new phenanthrenes (1-3), designated as 2-methoxy-1,6-dimethyl-5-vinyl-9, 10
      dihydrophenanthren-7-ol, 1,6-dimethyl-4,5-dihydropyrene-2,7-diol and 1-(3,7-
      dihydroxy-2,8-dimethyl-9,10-dihydrophenanthren-1-yl)ethanone, were isolated from
      the aerial parts of Juncus effusus. Their structures were determined by extensive
      spectroscopic experiments (NMR and MS) and comparing with those related known
      compounds. The antifungal and antibacterial activities of 1-3 were evaluated.
      Compound 1 showed remarkable antifungal activities against six agricultural
      pathogenic fungi (Rhizoctonia solani, Verticillium dahliae Kleb, Sclerotinia
      sclerotiorum, Gibberella saubinetii, Bipolaris zeicola, and Phytophthora
      parasitica) with minimum inhibitory concentration (MIC) values ranging from 3.125
      to 12.5 MUg/mL, and also displayed significant antibacterial activities against
      two human pathogenic bacteria (Bacterium paratyphosum B and Micrococcus
      lysodeikticus) with MIC values of 12.5 and 25 MUg/mL, respectively.

PMID- 30240846
TI  - Novel biomarkers in heart failure. What they add in daily clinical practice?

PMID- 30240845
TI  - New diterpenes from Salvia pseudorosmarinus and their activity as inhibitors of
      monoacylglycerol lipase (MAGL).
AB  - As a part of our ongoing research program on compounds from higher plants with
      lactate dehydrogenase (LDH) and monoacylglycerol lipase (MAGL) inhibitory
      activities, three new neoclerodane diterpene 12-deacetylsplendidin C (1),
      pseudorosmaricin (2), and 2-dehydroxysalvileucanthsin A (3) along with six known
      compounds were isolated from Salvia pseudorosmarinus aerial part extracts. Their
      structures were determined by spectroscopic and spectrometric techniques
      including 1D- and 2D NMR, and MS analyses. The isolated diterpenes were assayed
      for their inhibitory activity on LDH5 and MAGL, two enzymes covering key roles in
      the peculiar energetic metabolism of malignant tumours. All the assayed
      diterpenes showed negligible activity on LDH5, whereas the known jewenol A (4)
      displayed a moderate inhibition activity on MAGL, showing an IC50 value of
      46.8MUM and it proved to be a reversible MAGL inhibitor. Docking and molecular
      dynamic simulation studies where thus performed to evaluate the binding mode of 4
      within MAGL.

PMID- 30240847
TI  - The "ethos" and the "agony" of sham-controlled trials in cardiovascular medicine.

PMID- 30240848
TI  - The 2OGD Superfamily: Emerging Functions in Plant Epigenetics and Hormone
      Metabolism.

PMID- 30240849
TI  - Immunological alterations in frail older adults: A cross sectional study.
AB  - Frailty is a progressive physiologic decline in multiple body systems,
      characterized by loss of function, loss of physiologic reserve, and increased
      vulnerability to disease and death. This condition is induced by a complex and
      multifactorial interaction between genetic, biological, physical, psychological
      and environmental factors. To understand the interplay between the age-related
      decline of the immune response, and the upregulation of the inflammatory
      response, the so called inflammaging, we investigated the role of different
      inflammatory mediators on frailty status in the elderly. The study was performed
      in a population of 180 older adults (>=65 years), who were classified according
      to Fried's frailty phenotype. Plasma concentrations of neopterin, tryptophan,
      kynurenine, phenylalanine, tyrosine as well as kynurenine/tryptophan (Kyn/Trp)
      and phenylalanine/tyrosine (Phe/Tyr) ratios were analyzed as immune stimulation
      biomarkers. In addition, nitrite and C-reactive protein levels were measured as
      indicators of nitric oxide production and acute inflammation, respectively.
      Significant increases in neopterin, C-reactive protein and Kyn/Trp ratio, and
      decreases in tryptophan and nitrite concentrations in frail individuals compared
      with non-frail group were found. Both Kyn/Trp and Phe/Tyr ratios were
      significantly and positively correlated with neopterin. A positive correlation
      between kynurenine and tryptophan was also observed. Four parameters, i.e.,
      neopterin, tryptophan, nitrite and C-reactive protein, were found to be strongly
      related to frailty status, although only nitrite confirmed its role of predictor
      after multiple regression analysis, supporting its use as a potential biomarker
      of frailty. Further investigation is required to strengthen the consistence and
      reproducibility of these findings, and to establish this parameter as a clinical
      biomarker of frailty.

PMID- 30240850
TI  - Neural and muscular factors both contribute to plantar-flexor muscle weakness in
      older fallers.
AB  - Plantar-flexor muscles are key muscles in the control of postural sway. Older
      fallers present lower maximal plantar-flexor performance than older non-fallers;
      however, the mechanisms underlying this motor impairment remain to be elucidated.
      This study aimed to determine whether muscular and neural factors are both
      involved in the lower maximal plantar-flexor performance of older fallers. The
      maximal voluntary contraction (MVC) torque, resting twitch torque, voluntary
      activation level (VAL), and electromyographic (EMG) activities for the soleus,
      gastrocnemius medialis, gastrocnemius lateralis and tibialis anterior during
      plantar-flexor MVCs were recorded in 23 older non-fallers (age: 83.3 +/- 3.9
      years) and 25 older fallers (age: 84.0 +/- 4.1 years). The maximal plantar-flexor
      Hoffmann reflex normalized to the maximal motor potential (Hmax/Mmax) was
      measured to assess the efficacy of spinal transmission from the Ia-afferent
      fibers to the alpha-motoneurons. Older fallers presented lower plantar-flexor MVC
      torque, resting twitch torque, VAL and EMG activity (P < 0.05). No significant
      differences between older fallers and non-fallers were found for the Hmax/Mmax
      ratio and dorsi-flexor coactivation. The current findings showed for the first
      time that both neural and muscular factors associated with the plantar-flexors
      contributed to the specific alteration of maximal motor performance in older
      fallers. The lack of a difference in the Hmax/Mmax ratio indicated that the
      efficacy of spinal transmission from the Ia-afferent fibers to the alpha
      motoneurons was not involved in the lower voluntary muscle activation of older
      fallers. This suggests that supraspinal centers are likely to be involved in the
      lower voluntary muscle activation observed in older fallers.

PMID- 30240851
TI  - Computer-Based Intensity Measurement Assists Pathologists in Scoring Phosphatase
      and Tensin Homolog Immunohistochemistry - Clinical Associations in NSCLC Patients
      of the European Thoracic Oncology Platform Lungscape Cohort.
AB  - INTRODUCTION: Phosphatase and tensin homolog (PTEN) loss is frequently observed
      in NSCLC and associated with both phosphoinositide 3-kinase activation and
      tumoral immunosuppression. PTEN immunohistochemistry is a valuable readout, but
      lacks standardized staining protocol and cutoff value. METHODS: After an external
      quality assessment using SP218, 138G6 and 6H2.1 anti-PTEN antibodies, scored on
      webbook and tissue microarray, the European Thoracic Oncology Platform cohort
      samples (n = 2245 NSCLC patients, 8980 tissue microarray cores) were stained with
      SP218. All cores were H-scored by pathologists and by computerized pixel-based
      intensity measurements calibrated by pathologists. RESULTS: All three antibodies
      differentiated six PTEN+ versus six PTEN- cases on external quality assessment.
      For 138G6 and SP218, high sensitivity and specificity was found for all H-score
      threshold values including prospectively defined 0, calculated 8 (pathologists),
      and calculated 5 (computer). High concordance among pathologists in setting
      computer-based intensities and between pathologists and computer in H-scoring was
      observed. Because of over-integration of the human eye, pixel-based computer H
      scores were overall 54% lower. For all cutoff values, PTEN- was associated with
      smoking history, squamous cell histology, and higher tumor stage (p < 0.001). In
      adenocarcinomas, PTEN- was associated with poor survival. CONCLUSION: Calibration
      of immunoreactivity intensities by pathologists following computerized H-score
      measurements has the potential to improve reproducibility and homogeneity of
      biomarker detection regarding epitope validation in multicenter studies.

PMID- 30240852
TI  - Osimertinib versus Standard of Care EGFR TKI as First-Line Treatment in Patients
      with EGFRm Advanced NSCLC: FLAURA Asian Subset.
AB  - INTRODUCTION: Here we report efficacy and safety data of an Asian subset of the
      phase III FLAURA trial (NCT02296125), which compares osimertinib with standard of
      care (SoC) EGFR tyrosine kinase inhibitors (TKIs) in patients with previously
      untreated advanced NSCLC with tumors harboring exon 19 deletion (Ex19del)/L858R
      EGFR TKI-sensitizing mutations. METHODS: Eligible Asian patients (enrolled at
      Asian sites) who were at least 18 years of age (>=20 years in Japan) and had
      untreated EGFR-mutated advanced NSCLC were randomized 1:1 to receive osimertinib
      (80 mg, orally once daily) or an SoC EGFR TKI (gefitinib, 250 mg, or erlotinib,
      150 mg, orally once daily). The primary end point was investigator-assessed
      progression-free survival (PFS). The key secondary end points were overall
      survival, objective response rate, central nervous system efficacy, and safety.
      RESULTS: The median PFS was 16.5 versus 11.0 months for the osimertinib and SoC
      EGFR TKI groups, respectively (hazard ratio = 0.54, 95% confidence interval: 0.41
      0.72, p < 0.0001). The overall survival data were immature (24% maturity). The
      objective response rates were 80% for osimertinib and 75% for an SoC EGFR TKI.
      The median central nervous system PFS was not calculable for the osimertinib
      group and was 13.8 months for the SoC EGFR TKI group (hazard ratio = 0.55, 95%
      confidence interval: 0.25-1.17, p = 0.118). Fewer adverse events of grade 3 or
      higher (40% versus 48%) and fewer adverse events leading to treatment
      discontinuation (15% versus 21%) were reported with osimertinib versus with an
      SoC EGFR TKI, respectively. CONCLUSION: In this Asian population, first-line
      osimertinib demonstrated a clinically meaningful improvement in PFS over an SoC
      EGFR TKI, with a safety profile consistent with that for the overall FLAURA study
      population.

PMID- 30240853
TI  - Use of Pipeline Endovascular Device in Patients with Nickel Allergies.
AB  - BACKGROUND: Metal allergies affect a significant portion of the population;
      intracranial flow diverters contain many of the most commonly allergenic metals.
      Prior literature has suggested patch testing for all patients with documented or
      suspected metal allergies before intracranial flow diverter placement; however,
      there remains a paucity of reports of patients with documented metal allergies
      undergoing intracranial flow diversion. CASE DESCRIPTION: We report 2 patients
      with documented nickel allergies, confirmed via patch testing by a board
      certified allergist, and unruptured intracranial aneurysms that underwent
      treatment with the PED. Both patients developed contact dermatitis when a PED was
      affixed to their skin during their preoperative workup. Follow-up arteriography
      at 12 and 36 months post PED placement showed no evidence of in-stent stenosis or
      intimal hyperplasia, and both patients never developed systemic allergic
      reactions. CONCLUSIONS: In 2 patients with known nickel allergies and
      intracranial aneurysms treated with the PED, there were no clinically or
      radiographically apparent allergic reactions at greater than 2 years of follow
      up.

PMID- 30240854
TI  - Utility of the Vidian Canal in Endoscopic Skull Base Surgery: Detailed Anatomy
      and Relationship to the Internal Carotid Artery.
AB  - OBJECTIVE: To investigate key anatomic features of the vidian canal that have a
      critical role in planning and performing endoscopic skull base surgeries.
      METHODS: We reviewed skull base computed tomographic images of 640 consecutive
      subjects. Studies were analyzed in axial, coronal and sagittal planes. RESULTS:
      The mean (+/-SD) length of the vidian canal was 15.4 +/- 2.0 mm in female
      subjects and 16.6 +/- 1.7 mm in male subjects, and the difference between genders
      was statistically significant (P < 0.001). The most common rostral-caudal course
      of the vidian canal was medial to lateral and was followed by the straight
      course, tortuous course, and lateral-to-medial course. The frequency of
      pneumatization pattern from most common to least common was types 0, III, II and
      I. Of 342 evaluated sides, the vidian canal was located below the level of the
      anterior genu of petrous ICA in 303 (89%) sides, at same level with the anterior
      genu of petrous ICA in twenty-five(7%) sides, and above the level of the anterior
      genu of petrous ICA in fourteen(4.1%) sides. CONCLUSIONS: A variety of previously
      undefined features of the vidian canal that can alter the course of surgical
      procedure were defined. The position of the vidian canal with respect to the
      petrous internal carotid artery (ICA) was extensively described. From a surgical
      standpoint, a working room inferior and medial to the vidian canal might not
      always be a safe approach, because the vidian canal could be located superior to
      the level of the anterior genu of petrous ICA according to our findings in the
      present study.

PMID- 30240855
TI  - Long-Term Outcomes After Microscopic Anterior Cervical Foraminotomy with a
      Minimum 10-Year Follow-Up.
AB  - BACKGROUND: Microscopic anterior cervical foraminotomy (MACF) is a surgical
      technique for unilateral cervical radiculopathy that preserves segmental motion
      and avoids adjacent segmental degeneration, but little is known of its long-term
      outcomes. METHODS: A retrospective minimum 10-year follow-up study was conducted
      on patients treated by 1 surgeon. Clinical outcomes were assessed using a visual
      analog scale of neck and arm pain, Neck Disability Index, and Odom criteria.
      Surgical outcomes were assessed using additional procedure rates. Radiologic
      outcomes were estimated by measuring disc heights, segmental angles, and range of
      motion at the surgical level and adjacent segments, and so on. RESULTS: Of the 94
      patients who underwent MACF between January 2000 and December 2004 by 1 surgeon,
      69 were enrolled in this study. Median follow-up period was 11.9 years (range,
      10.0-14.5 years). Visual analog scales for neck or arm pain and Neck Disability
      Index improved significantly during follow-up period (P < 0.001). Also, according
      to the Odom criteria, an excellent or good outcome was achieved in 62 patients
      (89.9%) at final follow-up. An additional procedure was performed in 10 patients
      (14.5%) for symptom recurrence during the follow-up period. The only risk factor
      found to be related to the need for an additional procedure was a small
      preoperative range of motion at the surgical level (P = 0.018). Although mean
      disc height at the surgical level decreased significantly (from 6.23 +/- 1.10 to
      5.17 +/- 1.12 mm; P = 0.004), adjacent discs were not significantly affected.
      CONCLUSIONS: Although some radiologic results have shortcomings, the results of
      this study suggest that MACF has favorable long-term outcomes.

PMID- 30240856
TI  - Expanded Endoscopic Endonasal Approach to the Inframeatal Area: Anatomic Nuances
      with Surgical Implications.
AB  - BACKGROUND/OBJECTIVE: The inframeatal area represents a challenging region for
      skull base surgeons. Various surgical corridors have been described to access
      this area and frequently are used in combination. Recent studies describe the
      expanded endoscopic endonasal approach (EEA) as an established route for midline
      regions, particularly medial to the internal carotid arteries (ICA). We sought to
      evaluate the accessibility, maneuverability, and freedom of movement of the
      expanded endoscopic endonasal approach to the inframeatal region. METHODS: An EEA
      combining a middle and an inferior transclival corridor with an infrapetrous and
      a supracondylar lateral expansion was performed in 5 embalmed human cadaveric
      heads. The area of exposure and the surgical freedom to access the inframeatal
      area were calculated. The angle of attack and distances from the lacerum segment
      of the ICA to several anatomical targets also were measured. Our database was
      searched to select clinical case examples. RESULTS: The EEA provided an exposure
      area of 101.26 +/- 16.66 mm2 and an area of surgical freedom of 1208.50 +/-
      507.01 mm2. The angles of attack in both the sagittal and axial planes were wider
      at the lacerum segment of the ICA and narrower at the dural entrance zone of
      cranial nerves VII/VIII. Three chondrosarcomas are presented as case
      illustrations. CONCLUSIONS: The EEA is a feasible route to the inframeatal area.
      This approach provides a safe working corridor for lesions in this region, as
      shown by the anatomical and clinical findings presented here. Comparative studies
      and large case series are warranted to further establish its clinical value.

PMID- 30240858
TI  - The usefulness of dual volume visualization (three-dimensional digital
      subtraction angiography and cross-sectional imaging) for surgical planning in
      treating intracranial meningiomas: a case series and technical report.
AB  - OBJECTIVE: In pre-surgical planning for intracranial meningiomas, the
      relationship between tumors and adjacent vasculature must be identified. The
      purpose of this study was to evaluate the usefulness of three-dimensional digital
      subtraction angiography (3D-DSA) with dual volume visualization (DVV). METHODS:
      Between Feb. 2013 and April 2016, 26 patients with intracranial meningioma
      enrolled in this study. Two or 3 days before surgery, 3D-DSA with DVV was
      performed for pre-surgical planning. If necessary, the tumor was simultaneously
      embolized. RESULTS: Vascular supply and disfiguration observed by preoperative 3D
      DSA with DVV closely resembled those actually observed during surgery. All but
      two patients had total tumor resection (Simpson's grade 1 or 2). Three of 26
      patients had new neurologic deficits. CONCLUSIONS: 3D-DSA with DVV may be useful
      for preoperative planning by allowing the surgeon to identify the relationship
      between a tumor and peritumoral vasculature before meningioma surgery. Young
      neurosurgeons with little experience may benefit most from this technique.

PMID- 30240857
TI  - Craniopharyngiomas Primarily Involving the Hypothalamus: A Model of Neurosurgical
      Lesions to Elucidate the Neurobiological Basis of Psychiatric Disorders.
AB  - OBJECTIVE: This study provides a systematic review and meta-analysis of
      psychiatric disorders caused by craniopharyngiomas and the hypothalamic
      alterations underlying these symptoms. METHODS: We investigated a collection of
      210 craniopharyngiomas reported from 1823 to 2017 providing detailed clinical and
      pathologic information about psychiatric disturbances, including 10 of our own
      series, and compared the hypothalamic damage in this cohort with the present in a
      control cohort of 105 cases without psychiatric symptoms. RESULTS: Psychiatric
      disorders occurred predominantly in patients with craniopharyngiomas developing
      primarily at the infundibulotuberal region (45%) or entirely within the third
      ventricle (30%), mostly affecting adult patients (61%; P < 0.001). Most tumors
      without psychic symptoms developed beneath the third ventricle floor (53.5%; P <
      0.001), in young patients (57%; P < 0.001). Psychiatric disturbances were
      classified in 6 major categories: 1) Korsakoff-like memory deficits, 66%; 2)
      behavior/personality changes, 48.5%; 3) impaired emotional expression/control,
      42%; 4) cognitive impairments, 40%; 5) mood alterations, 32%; and 6) psychotic
      symptoms, 22%. None of these categories was associated with hydrocephalus. Severe
      memory deficits occurred with damage of the mammillary bodies (P < 0.001). Mood
      disorders occurred with compression/invasion of the third ventricle floor and/or
      walls (P < 0.012). Coexistence of other hypothalamic symptoms such as
      temperature/metabolic dysregulation or sleepiness favored the emergence of
      psychotic disorders (P < 0.008). Postoperative psychiatric outcome was better in
      strictly intraventricular craniopharyngiomas than in other topographies (P <
      0.001). A multivariate model including the hypothalamic structures involved, age,
      hydrocephalus, and hypothalamic symptoms predicts the appearance of psychiatric
      disorders in 81% of patients. CONCLUSIONS: Craniopharyngiomas primarily involving
      the hypothalamus represent a neurobiological model of psychiatric and behavioral
      disorders.

PMID- 30240859
TI  - Double-Layer TachoSil Packing for Management of Incidental Durotomy During
      Percutaneous Stenoscopic Lumbar Decompression.
AB  - BACKGROUND: Incidental durotomy (ID) during surgery for lumbar herniated disks or
      lumbar spinal stenosis is a serious complication that requires immediate
      recognition and repair. The incidence of ID during percutaneous endoscopic lumbar
      decompression has increased along with the demand for endoscopic spinal surgery.
      The management of ID during endoscopic surgery is more complicated and difficult
      than management during open surgery. A hemostatic agent, TachoSil (Nycomed, Linz,
      Austria), is used for control of local bleeding in several types of surgery, but
      its use in dural repair in endoscopic spinal surgery has not been described. CASE
      DESCRIPTION: We present 3 cases in which the double-layer TachoSil packing
      technique was used in the management of ID during percutaneous stenoscopic lumbar
      decompression. CONCLUSIONS: This case report reconfirms the efficacy and utility
      of TachoSil for IDs that occur during endoscopic spinal surgery and minimally
      invasive surgery. To our knowledge, this is the first report on the use and
      effectiveness of TachoSil for managing IDs during endoscopic spinal surgery. We
      hope that other surgeons will find this technique helpful in managing IDs.

PMID- 30240860
TI  - Measurement of Cervical Sagittal Alignment Parameters on X-Ray Films of Adults
      without Severe Spinal Deformity Whose Shoulder Hides the Lower Cervical Column.
AB  - OBJECTIVE: The Cobb angle between the lower endplate of C2 and C7 (C2L-C7L angle)
      is a traditional parameter used for the assessment of the cervical alignment.
      However, when the lower cervical column is masked by the shoulder, measurements
      are difficult. In the present study, we inspected 191 X-ray films, measured the
      Cobb angle between C2L and the endplates at the several levels of the lower
      cervical column, and assessed their usefulness of such measurements for the
      determination of cervical sagittal alignment. METHODS: We obtained X-ray films on
      191 patients ranging in age from 20 to 93 years. The Cobb angle between C2L and
      the C7 upper (C7U), the C6 lower (C6L), the C6 upper (C6U), and the C5 lower
      endplate (C5L) was measured and compared with the C2L-C7L angle. RESULTS: C7L was
      identified in 116 of 191 patients (60.7%). Except for C2L-C7U angle (P = 0.55),
      the difference in the mean between C2L-C7L angle and the angle between C2L and
      the other endplates was statistically significant (P < 0.05). There was a very
      strong correlation between C2L-C7L angle and C2L-C7U angle (r = 0.99), C2L-C6L
      angle (r = 0.96), C2L-C6U angle (r = 0.94), and C2L-C5L angle (r = 0.86).
      CONCLUSIONS: To measure the C2L-C7L angle on unclear X-ray films, C7U can be
      substituted for C7L. Our measurement data for the C6 and C5 endplates were
      statistically different; however, the correlation between the C2L-C7L angle and
      C2L-C6U angle, C2L-C6L angle or C2L-C5L angle was very strong. In patients with
      unclear lower vertebral bodies, cervical sagittal alignment can be predicted by
      using adjacent endplates.

PMID- 30240861
TI  - Novel Malleable Continuous Suction Tube Made of Ultrathin Stainless-Steel Foil
      Enclosed Between 2 Ultrafine Mesh Layers: Technical Note.
AB  - BACKGROUND: Bloodless dry fields are indispensable for successful and safe
      neurosurgical operations using microscopes. Appropriate irrigation and suction
      systems are needed to obtain clear surgical fields. We invented a novel malleable
      continuous suction tube to address this need. METHODS: We developed a malleable
      tube (MT) made of ultrathin stainless-steel foil (~5 MUm in thickness, 3.0 mm in
      diameter, 15 cm in length) contained between ultrafine stainless-steel wire mesh
      (50 MUm in diameter) woven tubes. The MT was applied in an intraoperative
      continuous fluid suction system, connecting it to a conventional vacuum system
      through a device. RESULTS: The MT can be placed at any part of the operative
      field, preferably close to its edges, without disturbing surgeon manipulation.
      This continuous suction system has been tested in neurosurgical operations and
      has shown excellent potential for maintaining the operative field clear and dry
      without any side effect or trauma on adjacent tissues. CONCLUSIONS: The newly
      developed malleable suction tube is effective for microsurgery.

PMID- 30240862
TI  - Clinical and Radiologic Features of Osteoporotic Spine Fracture with Delayed
      Neurologic Compromises.
AB  - OBJECTIVES: Osteoporotic spine fractures (OSFs) with delayed neurologic
      compromises (NCs) have been increasingly reported. Although several studies have
      addressed that the pathologic mechanism of NC involves nonunion and segmental
      instability, the risk factors remain unclear. Therefore, the purpose of this
      study was to assess the radiologic and clinical features of OSFs with delayed NC.
      METHODS: Thirty patients with delayed NC (group 1) were matched in a 1-to-1
      format with 30 patients without delayed NC (group 2) by age, bone mineral
      density, body mass index, and medical treatment for osteoporosis. Clinical and
      radiologic parameters were assessed to determine the risk factors related to
      delayed NC. Clinical outcomes were also compared between the 2 groups. RESULTS:
      Neurologic compromises were presented as myelopathy in 20 patients and
      radiculopathy in 10 patients. Initial kyphotic angle (KA) and height loss (HL)
      were significantly greater in group 1 (21.6 +/- 12.9 degrees vs. 10.5 +/- 8.6
      degrees, P = 0.0001 for KA; 55.8% +/- 15.2% vs. 19.9% +/- 10.9%, P = 0.0001 for
      HL). Fracture instability with intravertebral cleft, posterior wall involvement,
      midportion type of magnetic resonance classification, thoracolumbar level, and
      aortic calcification were significantly correlated with delayed NC. In
      multivariate analysis, initial HL (hazard ratio = 1.24; P = 0.012) and midportion
      type fracture (hazard ratio = 14.9: P = 0.03) were the independent risk factors
      related to delayed NC. In addition, clinical outcomes at the last follow-up were
      significantly better in group 2. CONCLUSIONS: Initial HL and midportion-type
      fracture were correlated with delayed NC following OSFs. Moreover, pre-existing
      stenotic lesions might be associated with delayed NC.

PMID- 30240863
TI  - Treatment Strategy for Tuberculum Sellae Meningiomas Based on a Preoperative
      Radiological Assessment.
AB  - BACKGROUND: Although there are several surgical approaches for the treatment of
      tuberculum sellae (TS) meningiomas, clear indications for non-large TS
      meningiomas are still lacking. METHODS: Our case series included 20 patients with
      TS meningiomas (<3 cm). We classified the tumors into 3 groups based on their
      radiologic relationship with the optic chiasm: type I, tumor with intact optic
      chiasm; type II, tumor with superiorly deviated optic chiasm; and type III, tumor
      with posteriorly deviated optic chiasm. Clinical outcomes, radiologic findings,
      and surgical approaches for the removal of each tumor type were retrospectively
      reviewed. RESULTS: Resections using a pterional approach, interhemispheric
      approach, and an endoscopic endonasal approach were performed in three groups of
      6, 7, and 7 patients. The rate of total tumor resection was equivalent across
      approaches, whereas postoperative visual dysfunction was observed in 1 patient
      (7.69%) undergoing a transcranial approach. Our evaluation of the sphenoid sinus
      shape across radiographs revealed that the patterns of bony wall elongation
      attached to these tumors significantly differed among tumor types, indicating
      that tumor origin and growth direction might affect the patterns of optic chiasm
      deviation. In addition, selective elongation of the TS provided a favorable
      surgical corridor for an endoscopic endonasal approach, especially in type II
      tumors. These results indicate that this tumor classification influenced surgical
      approach selection for non-large TS meningiomas. CONCLUSIONS: The aim of surgery
      is maximal tumor resection without causing visual dysfunction. The classification
      proposed here may predict surgical risk associated with meningioma resection and
      further inform the selection of a surgical approach.

PMID- 30240864
TI  - Preoperative Prediction of Solitary Fibrous Tumor/Hemangiopericytoma and
      Angiomatous Meningioma Using Magnetic Resonance Imaging Texture Analysis.
AB  - BACKGROUND: Solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is
      radiologically difficult to distinguish from meningioma, especially angiomatous
      meningioma. This study aimed to detect texture parameters to distinguish SFT/HPC
      from angiomatous meningioma using magnetic resonance imaging texture analysis
      with commercially available software. METHODS: We retrospectively investigated
      textural parameters in 43 newly diagnosed SFTs/HPCs, angiomatous meningiomas, and
      other World Health Organization (WHO) grade I meningiomas treated at Keio
      University Hospital. For T1 contrast-enhanced, T2, and apparent diffusion
      coefficient (ADC) images, texture analyses were performed. Regions of interest
      were drawn manually with reference to the greater signal on contrast-enhanced T1
      weighted images. ADC values and texture parameters, including kurtosis, skewness,
      and entropy, were evaluated and compared between these 3 groups. RESULTS: The
      mean ADC value was significantly high in angiomatous meningioma, compared with
      SFT/HPC and other WHO grade I meningioma. ADC entropy was highest in SFT/HPC,
      followed by angiomatous and other WHO grade I meningioma. T2 skewness was
      significantly high in SFT/HPC, compared with angiomatous and other WHO grade I
      meningioma. T1 contrast-enhanced skewness was significantly low in angiomatous
      meningioma, compared with other WHO grade I meningioma. Mean ADC value
      distinguished SFT/HPC from angiomatous meningioma with a positive predictive
      value (PPV) of 62.5% and specificity of 62.5%. ADC entropy distinguished SFT/HPC
      from angiomatous meningioma with a PPV of 100% and specificity of 100%. ADC
      skewness distinguished SFT/HPC from angiomatous meningioma with a PPV of 66.7%
      and specificity of 71.4%. CONCLUSIONS: This study demonstrated that magnetic
      resonance imaging texture analysis was useful for distinguishing SFT/HPC from
      meningioma, especially angiomatous meningioma.

PMID- 30240865
TI  - What Is the Best Electrophysiologic Marker of the Outcome of Subthalamic Nucleus
      Stimulation in Parkinson Disease?
AB  - OBJECTIVE: Deep brain stimulation of the subthalamic nucleus (STN) is advocated
      in patients with advanced Parkinson disease. Intraoperative microelectrode
      recordings (MER) and stimulation or imaging are applied to confirm electrode
      targeting. The study objective was to evaluate which intraoperative
      electrophysiologic marker, MER, stimulation, or local field potentials (LFP) was
      the most predictive of the clinical efficacy. METHODS: Efficacy was determined
      with lateralized motor scores of Movement Disorders Society-Unified Parkinson's
      Disease Rating Scale in 36 patients (OFF-drug/ON-stimulation 1 year after surgery
      vs. OFF-drug before surgery). Trajectory lengths in STN were determined from MER.
      Stimulation was increased up to the thresholds of first decrease, of complete
      suppression of rigidity, and of excitation of pyramidal motor tract. beta
      oscillations (11-31 Hz) were computed from LFP of the electrode macrocontact.
      Univariate and multivariate analyses were computed. RESULTS: Motor improvements
      were linked to trajectory lengths in STN (R2 = 0.17; P > 0.005). No significant
      relationship was found for thresholds of first decrease or suppression in
      rigidity or for motor tract excitation (R2 < 0.03, P > 0.05). Motor improvements
      were most linked to beta oscillation increases (R2 = 0.57, P < 0.005, linear
      regression; R2 = 0.84, P < 0.0001, post hoc sigmoid regression). beta
      oscillations appeared more predictive than length (beta: t = 5.4, P < 0.001;
      length: t = 2.70, P < 0.03). Improvements were also slightly predicted by
      preoperative scores (R2 = 0.13; P < 0.005). CONCLUSIONS: Motor improvements
      emerged as most related to beta oscillations, before trajectory length within the
      STN, whereas stimulation thresholds of rigidity or of motor tract excitation
      failed to show any relationship. The study encourages LFP measurement to confirm
      STN electrode location.

PMID- 30240867
TI  - Intracranial Meningeal Rosai-Dorfman Disease Mimicking Multiple Meningiomas: 3
      Case Reports and a Literature Review.
AB  - BACKGROUND: Rosai-Dorfman disease (RDD) is a benign, self-limiting, and
      nonneoplastic histiocytic proliferative disorder with a poorly defined
      pathogenesis. Central nervous system involvement is extremely rare, particularly
      cases with multiple intracranial masses. There is no consensus on optimal
      treatment and management of RDD. CASE DESCRIPTION: In case 1, a 39-year-old man
      presented with headaches and paroxysmal convulsions of the limbs. Magnetic
      resonance imaging showed multiple solid masses located at the right
      frontoparietal and left frontal meningeal regions. The masses were surgically
      removed for staging, and the histologic diagnosis was consistent with RDD. In
      case 2, a 53-year-old man was admitted with epileptic seizures. Magnetic
      resonance imaging revealed multiple, homogeneously enhancing masses in the left
      parietal, temporal, and occipital meningeal regions. The largest mass was
      surgically removed, and histopathologic examination confirmed RDD. In case 3, a 9
      year-old girl was admitted with bilateral exophthalmos and incomplete eyelid
      closure. Magnetic resonance imaging displayed multiple, heterogeneously enhancing
      masses in the right parietal meningeal region. All masses were surgically
      removed, and the histopathologic diagnosis was RDD. CONCLUSIONS: RDD with
      multiple isolated intracranial foci is rare but should be considered in the
      differential diagnosis when multiple meningiomas are suspected in children and
      adults. Preoperative diagnosis is challenging, and definitive diagnosis requires
      immunohistochemical examination. Surgical resection is the most effective therapy
      for rapid relief of symptoms.

PMID- 30240866
TI  - BRAF V600E, TERT, and IDH2 Mutations in Pleomorphic Xanthoastrocytoma:
      Observations from a Large Case-Series Study.
AB  - BACKGROUND: Anaplastic pleomorphic xanthoastrocytoma (PXA) was added to grade III
      glial tumors as a distinct entity in the 2016 World Health Organization (WHO)
      classification of tumors of the central nervous system. We retrospectively
      reviewed and analyzed 55 pathologically confirmed PXA cases according to the
      newest WHO classification to better clarify the clinical, molecular, and
      prognostic features of this rare neoplasm. METHODS: In total, 55 pathologically
      confirmed PXA cases according to the newest WHO classification were
      retrospectively reviewed and analyzed. After sequencing for BRAF, TERT, IDH1/2,
      and H3F3A, survival analysis was performed to determine the factors affecting
      survival. RESULTS: The patients with BRAF V600E mutations were generally younger
      than those without it, although not statistically significant (27.9 +/- 15.4
      years and 37.1 +/- 17.0 years, respectively, P = 0.054). TERT promoter mutation
      frequency in PXA was lower than in patients with anaplastic PXA although not
      statistically significant (4.4% and 28.6%, P = 0.083). One instance of PXA with
      IDH2 mutation, and no IDH1 and H3F3A mutations were found. In terms of prognosis,
      patients with anaplastic PXA had shorter overall survival and progression-free
      survival compared with patients with PXA. The subgroup with gross total resection
      had a longer median OS (not reached vs. 60.0 months, P = 0.0221) and PFS (not
      reached vs. 60.0 months, P = 0.0232) compared with patients with PXA with
      subtotal resection. CONCLUSIONS: The identification of BRAF V600E, TERT, and IDH2
      mutations in PXA expands our molecular understanding of PXA. Patients with PXA
      with gross total resection achieve good outcomes.

PMID- 30240868
TI  - Glossopharyngeal Neuralgia Treatment Outcomes After Nerve Section, Microvascular
      Decompression, or Stereotactic Radiosurgery: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Glossopharyngeal neuralgia (GPN) is a rare neuralgic pain syndrome
      amenable to neurosurgical treatments, including nerve section (NS), microvascular
      decompression (MVD), and stereotactic radiosurgery (SRS). However, thorough
      comparisons of the modalities have not been performed to date. The objective of
      the present study was to compare the pain and complication outcomes after these
      approaches to GPN. METHODS: Searches of 7 electronic databases from inception to
      June 2018 were conducted following the appropriate guidelines. The incidence
      rates (IRs) of short-term (<=3 months) and long-term (>=12 months) pain relief
      and complications were extracted and analyzed using a meta-analysis. Meta
      regression was used to assess for heterogeneity. RESULTS: A total of 792 GPN
      cases managed by NS, MVD, or SRS were described by 6, 11, and 6 studies,
      reporting outcomes for 282 (36%), 446 (56%), and 67 (8%) cases. The short-term
      pain relief rate was highest after NS postoperatively (IR, 94%; 95% confidence
      interval [CI], 88%-98%) and lowest after SRS at 3 months postoperatively (IR,
      80%; 95% CI, 68%-96%). The postoperative complication rate was greatest after MVD
      (IR, 26%; 95% CI, 16%-38%) and lowest after SRS (IR, 0%; 95% CI, 0%-4%). The long
      term pain relief rate was greatest after NS (IR, 96%; 95% CI, 91%-99%) and lowest
      after SRS (IR, 82%; 95% CI, 67%-94%). Statistically significant differences
      between the approaches were found for each outcome. CONCLUSION: Neurosurgical
      treatment of GPN is frequently performed by 1 of 3 modalities with unique
      outcomes profiles. NS might provide the most favorable treatment response, with
      respect to short- and long-term pain relief and postoperative outcomes.

PMID- 30240869
TI  - Quantifying Hemodynamic Changes in Moyamoya Disease Based on Two-Dimensional Cine
      Phase-Contrast Magnetic Resonance Imaging and Computational Fluid Dynamics.
AB  - OBJECTIVE: To investigate hemodynamic changes in moyamoya disease (MMD) via two
      dimensional cine phase-contrast magnetic resonance imaging and computational
      fluid dynamics. METHODS: In 18 patients with MMD and 10 healthy control subjects,
      phase-contrast magnetic resonance imaging was performed to quantify flow rate of
      main supplying arteries, including internal carotid arteries (ICAs) and vertebral
      arteries. Mean flow rate in these vessels was adopted as the patient-specific
      boundary condition for computational fluid dynamics simulation of the circle of
      Willis in MMD and control groups. Pressure drop in both ICAs and their
      difference, wall shear stress and secondary flow in the carotid siphon of ICAs,
      and flow rate and size of posterior communicating arteries (PComAs) were compared
      between MMD and control groups. Four patients with MMD underwent follow-up scans
      for longitudinal comparison. RESULTS: Phase-contrast magnetic resonance imaging
      data revealed significantly different flow rate in the left ICA and right
      vertebral arteries between MMD and control groups. Computational fluid dynamics
      simulation demonstrated similar wall shear stress and similar secondary flow of
      both ICAs but significantly higher pressure drop in left ICA, higher pressure
      drop difference between left ICA and right ICA, and higher flow rate in PComAs in
      patients with MMD compared with control subjects. Significantly increased size of
      left PComA in patients with MMD was also found. Follow-up results confirmed that
      the combination of pressure drop difference, flow rate, and size of PComAs can
      potentially assist long-term prognosis after surgery. CONCLUSIONS: Pressure drop
      difference, flow rate, and size of PComAs can be used to evaluate impairments in
      cerebrovascular reserve and indicate long-term prognosis in MMD.

PMID- 30240870
TI  - MIB Index as Predictor of Recurrence in Sporadic Vestibular Schwannomas.
AB  - OBJECTIVE: Nearly 9.2% of vestibular schwannomas (VS) recur. We evaluate the
      association of cell proliferative markers like MIB with recurrence in VS.
      METHODS: Retrospective data of 144 consecutive patients who underwent surgical
      excision for sporadic VS between January 2010 and July 2015 were collected.
      Comparison between groups based on recurrence of VS was done. RESULTS: The
      average age of the study population was 43.95 +/- 12.86 years with 77 (53.5%)
      men. The average maximal diameter of VS was 40.25 +/- 7.23 mm. Gross total
      resection was done in 52 (36.1%) patients. While near total resection was
      performed in 81 (56.3%) patients, the remaining 11 (7.6%) patients underwent a
      subtotal resection. The mean follow-up period was 37.99 +/- 10.09 months (24-60).
      Recurrence of VS was observed in 18 (12.5%) patients. There was no difference
      between the groups for diameter of the tumor (42.22 +/- 8.04 vs. 39.64 +/- 7.00
      mm; P = 0.191). The average MIB index value was higher in patients with
      recurrence of tumor at follow-up (4.78 +/- 5.77 vs. 1.89 +/- 1.48 mm; P < 0.001).
      There was no difference between the groups for extent of resection or
      postoperative complications. MIB was the only significant predictor for
      recurrence (beta = 1.355 (1.07-1.78; confidence interval 95%); P = 0.031). On
      receiver operating characteristic curves, a cutoff value of 3.5% for MIB showed a
      specificity of 84.1%. CONCLUSIONS: MIB index >=3.5% is associated with recurrence
      in VS. Maximal diameter of the tumor and extent of resection are perhaps not
      associated with recurrence of VS.

PMID- 30240871
TI  - High prevalence and narrow host range of haemosporidian parasites in Godlewski's
      bunting (Emberiza godlewskii) in northern China.
AB  - Avian haemosporidian parasites are highly diverse, have a wide range of host
      specificity, and reveal diverse compatibility with regard to host range and
      geographical distribution. Therefore, understanding haemosporidian parasite
      diversity in different host species and different regions is crucial. A survey of
      the haemosporidian parasite in 186 Godlewski's buntings in Beijing was conducted
      to compare infection patterns between Godlewski's bunting, local passerines and
      the global avian host. High prevalence (88.7%) was found in this bunting species,
      and it displayed annual stability during the sample period. Most of the
      infections were caused by four dominant lineages. In comparison with other
      lineages in local passerines, these four dominant lineages were relative
      specialists. Within these dominant lineages, three were clustered with lineages
      of morphological species. The findings suggest that high vector abundance and the
      compatibility of dominant lineages may play important roles in high
      haemosporidian prevalence, and the narrow host range of dominant lineages may be
      due to coevolution of this resident bunting and the parasites.

PMID- 30240872
TI  - Molecular and histopathological features of Cryptosporidium ubiquitum infection
      in imported chinchillas Chinchilla lanigera in Japan.
AB  - Long-tailed chinchillas Chinchilla lanigera are popular rodent species kept both
      in households, where they are hand-raised as pets, and in zoological facilities.
      From January 2016 to February 2017, 13 juvenile chinchillas from five facilities
      in Japan were diagnosed with cryptosporidiosis at the animal hospital. Eight of
      the cases were fatal. All of the animals were imported from the Czech Republic by
      the same vendor. Histopathological and multilocus sequence analyses using 18S
      ribosomal RNA, actin, 70-kDa heat shock protein, and 60-kDa glycoprotein genes
      confirmed Cryptosporidium ubiquitum of subtype XIId as the etiological agent.
      Multilocus analysis demonstrated the presence of two new sequence types closely
      related to the C. ubiquitum Xlld strain isolated from a human in the USA. This
      study indicated that potentially zoonotic Cryptosporidium is widespread and may
      have caused a high number of deaths among imported juvenile chinchillas.

PMID- 30240873
TI  - Salary and Resources Provided to Junior Faculty in Radiation Oncology.
AB  - PURPOSE: Given the importance of access to key resources to ensure future
      academic success, we seek to describe what is currently provided to junior
      faculty in radiation oncology. METHODS AND MATERIALS: We present descriptive
      analyses from a survey of academic radiation oncologists in the United States and
      Canada who were within 5 years of board certification. We used a pretested
      questionnaire evaluating time, space, staff, start-up funding, and compensation.
      RESULTS: We surveyed 347 faculty, with a response rate of 64% (n = 221).
      Respondents reported working an average of 56 hours per week. Most respondents
      (59.2%) reported that that their research time was "poorly" or "not at all"
      protected. Most perceived adequate access to space (75.7%) and equipment (73.6%).
      A substantial proportion perceived inadequate or no access to support from grant
      administrators (47.9%) or statisticians (55.5%). A third (33.6%) reported having
      a research assistant, and 22.2% received start-up research funding. CONCLUSIONS:
      These findings suggest perceived needs for protected time, grants administration,
      and statistical support among junior faculty in radiation oncology.

PMID- 30240874
TI  - A randomized controlled trial of different levels of coach support in an online
      intervention for relationship distress.
AB  - Recently-developed online interventions for relationship distress show promising
      results; however, the degree to which paraprofessionals need to be involved with
      web-based interventions for relationship distress remains unclear. The present
      study sought to determine if varying levels of coach contact moderated gains
      during the online OurRelationship program, which was previously shown to be
      effective by Doss and colleagues (2016). Three hundred fifty-six heterosexual
      couples (712 individuals) enrolled in the OurRelationship program and were
      randomized to a Low or High coach support condition. Couples in both conditions
      experienced significant improvements in relationship satisfaction as well as
      depressive and anxious symptoms (within-group d = 0.43-0.71). Using intent-to
      treat analyses, there were no significant differences over the intervention
      between groups in improvements in relationship satisfaction or depressive
      symptoms. However, couples in the high-support condition reported significantly
      greater decreases in anxious symptoms. Furthermore, couples in the low-support
      group were significantly more likely to drop out prematurely. Overall, results
      indicated that minimal coach support may be a viable option to facilitate
      dissemination of online interventions for relationship distress. This study was
      registered on ClinicalTrials.gov (NCT03332875).

PMID- 30240875
TI  - Parkinson's disease research: adopting a more human perspective to accelerate
      advances.
AB  - Parkinson's disease (PD) affects 1% of the population over 60 years old and, with
      global increases in the aging population, presents huge economic and societal
      burdens. The etiology of PD remains unknown; most cases are idiopathic, presumed
      to result from genetic and environmental risk factors. Despite 200 years since
      the first description of PD, the mechanisms behind initiation and progression of
      the characteristic neurodegenerative processes are not known. Here, we review
      progress and limitations of the multiple PD animal models available and identify
      advances that could be implemented to better understand pathological processes,
      improve disease outcome, and reduce dependence on animal models. Lessons learned
      from reducing animal use in PD research could serve as guideposts for wider
      biomedical research.

PMID- 30240876
TI  - The leukotriene signaling pathway: a druggable target in Alzheimer's disease.
AB  - The underlying pathology of Alzheimer's disease (AD) is complex and includes,
      besides amyloid beta (Abeta) plaque depositions and neurofibrillary tangles,
      brain atrophy and neurodegeneration, neuroinflammation, impaired neurogenesis,
      vascular and blood-brain barrier (BBB) disruptions, neurotransmitter disbalances,
      and others. Here, we hypothesize that such complex pathologies can only be
      targeted efficiently through pleiotropic approaches. One interesting drug target
      is the leukotriene pathway, which mediates various aspects of AD pathology.
      Approaching this pathway at different levels with genetic and pharmacological
      tools demonstrated beneficial outcomes in several in vivo studies using different
      mouse models of AD. Here, we review the current literature on the leukotriene
      signaling pathway as a target for drug development in AD.

PMID- 30240877
TI  - The effect of surgically implanted metallic bullet fragments on the
      intervertebral disc using a canine model?.
AB  - PURPOSE: To characterize the gross, histologic, and systemic changes caused by
      implantation of metal fragments commonly used in commercial bullets into the
      intervertebral disc. BACKGROUND CONTEXT: Long-term complications of retained
      bullet fragments in the spine have been documented in the literature; however,
      the impact of different metal projectiles on the intervertebral disc has not been
      described. This study was performed to assess the local effects of the metallic
      bullet fragments on the intervertebral disc and their systemic effects regarding
      metal ion concentrations in serum and solid organs. STUDY DESIGN: Animal Model
      Study. METHODS: Funding for this project was provided by the Cervical Spine
      Research Society in the amount of $10,000. Copper, lead, and aluminum alloys from
      commercially available bullets were surgically implanted into sequential
      intervertebral discs in the lumbar spine of six canines. Kirschner wire
      implantation and a sham operation were performed as controls. Radiographs were
      performed to confirm the location of the bullets. Animals were sacrificed at 4,
      6, and 9 months postimplantation. Whole blood, plasma, cerebrospinal fluid,
      kidney tissue, and liver tissue samples were analyzed for copper and lead
      concentrations. Histologic and gross samples were examined at the time of
      sacrifice. RESULTS: Significant tissue reactions were noted in the discs exposed
      to copper and lead. Copper resulted in significantly more severe disc
      degeneration than either the lead or aluminum alloy. In the short interval follow
      up of this study, no statistically significant trend was observed in whole blood,
      plasma, cerebrospinal fluid, and tissue levels. CONCLUSION: This study
      demonstrates that the canine intervertebral disc is differentially susceptible to
      metallic fragments depending on the composition. Trends were noted for increasing
      levels of lead and copper in liver tissue samples although statistical
      significance could not be reached due to short time interval and small sample
      size. The metallic composition of retained fragments can be a determining factor
      in deciding on surgical intervention.

PMID- 30240878
TI  - Re: Return to work following surgery for lumbarradiculopathy-is there a need for
      postoperative rehabilitation?

PMID- 30240879
TI  - Quality assurance of colonoscopy within the Dutch national colorectal cancer
      screening program.
AB  - Colorectal cancer (CRC) screening is capable of reducing CRC-related morbidity
      and mortality. Colonoscopy is the reference standard to detect CRC, also
      providing the opportunity to detect and resect its precursor lesions: colorectal
      polyps. Therefore, colonoscopy is either used as a primary screening tool or as a
      subsequent procedure after a positive triage test in screening programs based on
      non-invasive stool testing or sigmoidoscopy. However, in both settings,
      colonoscopy is not fully protective for the occurrence of post-colonoscopy CRCs
      (PCCRCs). Because most PCCRCs are the result of colonoscopy-related factors, a
      high-quality procedure is of paramount importance to assure optimal effectiveness
      of CRC screening programs. For this reason, at the start of the Dutch fecal
      immunochemical test (FIT)-based screening program, quality criteria for
      endoscopists performing colonoscopies in FIT-positive screenees, as well as for
      endoscopy centers, were defined. In conjunction, an accreditation and auditing
      system was designed and implemented. In this report, we describe the quality
      assurance process for endoscopists participating in the Dutch national CRC
      screening program, including a detailed description of the evidence-based quality
      criteria. We believe that our experience might serve as an example for
      colonoscopy quality assurance programs in other CRC screening programs.

PMID- 30240880
TI  - Annular pancreas: endoscopic and pancreatographic findings from a tertiary
      referral ERCP center.
AB  - BACKGROUND AND AIMS: Annular pancreas is a congenital anomaly whereby pancreatic
      tissue encircles the duodenum. Current knowledge of endoscopic findings of
      annular pancreas is limited to small case series. The aim of this study was to
      describe the endoscopic and pancreatographic findings of patients with annular
      pancreas at a large tertiary care ERCP center. METHODS: This is a retrospective
      observational study. Our Institutional Review Board-approved, prospectively
      collected ERCP database was queried for cases of annular pancreas. The electronic
      medical records were searched for patient and procedure-related data. RESULTS:
      From January 1, 1994, to December 31, 2016, 46 patients with annular pancreas
      underwent ERCP at our institution. Index ERCP was technically successful in 42
      patients (91.3%), and technical success was achieved in all 46 patients (100%)
      after 2 attempts, when required. A duodenal narrowing or ring was found in most
      patients (n = 39, 84.8%), yet only 2 (4.3%) had retained gastric contents.
      Pancreas divisum was found in 21 patients (45.7%), 18 of which were complete
      divisum. Pancreatobiliary neoplasia was the indication for ERCP in 7 patients
      (15.2%). Pancreatographic findings consistent with chronic pancreatitis were
      noted in 15 patients (32.6%) at the index ERCP. CONCLUSION: This is the largest
      series describing the endoscopic and pancreatographic findings of patients with
      annular pancreas. We found that 45.7% of patients had concurrent pancreas
      divisum. Endoscopic therapy was successful in most patients at our institution
      after 1 ERCP, and in all patients after a second ERCP. Nearly one-third of
      patients had findings consistent with chronic pancreatitis at the time of index
      ERCP. It is unclear whether this may be a feature of the natural history of
      annular pancreas.

PMID- 30240881
TI  - LPS promote Osteosarcoma invasion and migration through TLR4/HOTAIR.
AB  - OBJECTIVES: Osteosarcoma is one of common malignant tumors worldwide in the
      metaphysis of teenagers. The role of lncRNAs in Osteosarcoma has become an
      emerging area of research. MATERIALS AND METHODS: Cell migration and invasion
      were analyzed in Osteosarcoma cell following knockdown or overexpression by
      transfection with small interfering RNA (siRNA) or treated with LPS. Western
      blotting and Real-time RT-PCR methods were used to analyze the effects of LPS on
      EMT. RESULTS: We discovered that LPS could regulate cell migration and invasion
      and promote EMT. At the same time, LPS could regulate the expression of TLR4 and
      HOTAIR. In addition, knockdown of the expression of TLR4 partially reverses the
      promotion of cell invasion induced by LPS. CONCLUSIONS: Our results indicated
      that LPS coordinate the Osteosarcoma through TLR4/HOTAIR.

PMID- 30240882
TI  - A review study: Computational techniques for expecting the impact of non
      synonymous single nucleotide variants in human diseases.
AB  - Non-Synonymous Single-Nucleotide Variants (nsSNVs) and mutations can create a
      diversity effect on proteins as changing genotype and phenotype, which interrupts
      its stability. The alterations in the protein stability may cause diseases like
      cancer. Discovering of nsSNVs and mutations can be a useful tool for diagnosing
      the disease at a beginning stage. Many studies introduced the various predicting
      singular and consensus tools that based on different Machine Learning Techniques
      (MLTs) using diverse datasets. Therefore, we introduce the current comprehensive
      review of the most popular and recent unique tools that predict pathogenic
      variations and Meta-tool that merge some of them for enhancing their predictive
      power. Also, we scanned the several types computational techniques in the state
      of-the-art and methods for predicting the effect both of coding and noncoding
      variants. We then displayed, the protein stability predictors. We offer the
      details of the most common benchmark database for variations including the main
      predictive features used by the different methods. Finally, we address the most
      common fundamental criteria for performance assessment of predictive tools. This
      review is targeted at bioinformaticians attentive in the characterization of
      regulatory variants, geneticists, molecular biologists attentive in understanding
      more about the nature and effective role of such variants from a functional point
      of views, and clinicians who may hope to learn about variants in human associated
      with a specific disease and find out what to do next to uncover how they impact
      on the underlying mechanisms.

PMID- 30240884
TI  - New-Onset Asthma in Adults: What Does the Trigger History Tell Us?
AB  - BACKGROUND: Adult-onset asthma is an important asthma phenotype and, in contrast
      to childhood asthma, is often associated with specific triggers of onset. It is
      unknown whether these triggers correspond with specific phenotypic
      characteristics or predict a specific asthma outcome. OBJECTIVE: To compare
      clinical, functional, and inflammatory characteristics between patients with
      different triggers of asthma onset, and relate these triggers to asthma outcome.
      METHODS: Two hundred adults with recently diagnosed (<1 year) asthma were
      prospectively followed for 5 years. The trigger of asthma onset was patient
      reported and defined by the question: "What, in your opinion, elicited your
      asthma?" Asthma remission was defined as no asthma symptoms and no asthma
      medication use for >=1 year. Kruskal-Wallis and Fisher's exact test were used to
      compare categories containing >10 patients. RESULTS: Ten categories of triggers
      were identified, of which 5 contained >10 patients. Clinical and inflammatory
      characteristics and remission rates differed significantly between categories.
      "New allergic sensitization" (11%) was associated with mild atopic asthma and a
      relatively young age at onset; "pneumonia" (8%) with previous smoking, low IgE,
      and the highest remission rates (one third); "upper respiratory symptoms" (22%)
      with high exhaled NO and eosinophilia; "no trigger identified" (38%) did not show
      any specific characteristics; and "stressful life event" (7%) with high
      medication usage, low type 2 markers, and no disease remission. CONCLUSIONS:
      Patients with adult-onset asthma can be characterized by the trigger that
      seemingly incited their asthma. These triggers might represent underlying
      mechanisms and may be important to phenotype patients and predict disease
      outcome.

PMID- 30240883
TI  - Identification of SPP1 as a promising biomarker to predict clinical outcome of
      lung adenocarcinoma individuals.
AB  - We identified and investigated the prognostic value of secreted phosphoprotein 1
      (SPP1) in lung adenocarcinoma (LUAD) patients and evaluate the relationship
      between the SPP1 expression level and clinical characteristics. First, SPP1 was
      identified through four LUAD datasets in GEO database and validated by the TCGA
      database. Then a total of 149 lung adenocarcinoma patients were included, as well
      as their clinicopathological characteristics collected in the study. The
      expression levels of SPP1 and adjacent normal tissues were assessed by
      immunohistochemistry. The association between SPP1 and its prognostic value was
      systematically evaluated. Results showed high SPP1 level predicted poorer LUAD
      survival by univariate Cox analysis (P = 0.017), and the multivariate result was
      also significant (P = 0.021). Subgroup analysis suggested the prognostic value of
      SPP1 was significant in stage T1 (log rank P = 0.011), stage N0 (log rank P =
      0.046) and stage N1 (log rank P = 0.009) patients. After including these markers
      into a nomogram, the Harrell's C-index of the nomogram was 0.694. In summary, our
      findings suggest that SPP1 is an independent biomarker with prognostic
      significance in LUAD.

PMID- 30240885
TI  - Initiating yellow jacket venom immunotherapy with a 100-MUg dose: A challenge?

PMID- 30240886
TI  - Self-reported anaphylaxis to packaged foods in Australia.

PMID- 30240887
TI  - Antibiotic Allergy Labels in Children Are Associated with Adverse Clinical
      Outcomes.
AB  - BACKGROUND: Self-reported antibiotic allergies are common among hospitalized
      adults and children. However, there is a paucity of studies investigating the
      impact of an antibiotic allergy label in childhood. OBJECTIVE: To investigate the
      impact of antibiotic allergy labeling on clinical outcomes in children. METHODS:
      A retrospective study was conducted in a major pediatric tertiary hospital to
      capture inpatient admissions (N = 1672) in April 2014 and April 2015. Data,
      collected by chart review, included documented antibiotic allergy labels,
      antibiotic prescriptions, admitting specialty, hospital length of stay, and
      hospital readmissions. RESULTS: Of the 1672 pediatric patients surveyed, 58.1%
      were male and 44.8% were prescribed antibiotics. Antibiotic allergy labels were
      recorded in 5.3% of patients; most were beta-lactam allergy labels (85%), mostly
      to unspecified penicillins. There was an increasing incidence of antibiotic
      allergy label with age, which was statistically significant (P < .001); no sex
      effect was seen. Patients with antibiotic allergy labels received more macrolide
      (P = .045), quinolones (P = .01), lincosamide (P < .001), and metronidazole (P =
      .009) antibiotics than did patients without an antibiotic allergy label. After
      adjusting for patient age, sex, principal diagnosis, and admitting specialty,
      children with any antibiotic or beta-lactam allergy label had longer hospital
      stays (odds ratio, 1.62; 95% CI, 1.05-2.50; P = .03) with a mean length of
      hospital stay of 3.8 days for those without a label and 5.2 days for those with a
      beta-lactam allergy label. CONCLUSIONS: This is the first study demonstrating the
      negative impact of antibiotic allergy labels on clinical outcomes in children, as
      evidenced by significant alternate antibiotic use and longer hospital stays.

PMID- 30240889
TI  - Predictors of inhaled corticosteroid taper failure in adults with asthma.

PMID- 30240890
TI  - Practice makes perfect: High performance gains in older adults engaged in
      selective attention within and across sensory modalities.
AB  - Selective attention has been found to decline with aging, possibly depending on
      the sensory modality through which targets and distractors are presented. We
      investigated the capacity of older adults to improve performance on visual and
      auditory selective attention tasks. 31 younger (mean age = 22.8 years, SD = 2.1)
      and 29 older participants (mean age = 69.5 years, SD = 5.8) performed visual and
      auditory tasks with and without unimodal and cross-modal distraction across five
      practice sessions. Reaction time decreased with practice in both age groups.
      Strikingly, this performance improvement was similar across the age groups.
      Moreover, distractor modality did not affect performance gains in either age
      group. Older adults were disproportionally affected by cross-modal visual
      distraction, however, corroborating previous studies. This age-related effect was
      mitigated during the practice sessions. Finally, there was no transfer of
      practice to neuropsychological test performance. These results suggest a high
      capacity of older individuals to improve selective attention functions within and
      across sensory modalities.

PMID- 30240892
TI  - Analysis of Midesophageal Biopsies Increases Sensitivity of Detection of
      Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis (EoE) is defined by the presence of abundant eosinophils
      in the squamous epithelium of the esophagus. There has been remarkable progress
      recently in the understanding of the pathogenesis, diagnosis, and treatment of
      EoE.1 Because undiagnosed EoE leads to an increase in fibrostenotic complications
      including strictures, timely diagnosis is critical.2.

PMID- 30240891
TI  - States of focused attention and sequential action: A comparison of single session
      meditation and computerised attention task influences on top-down control during
      sequence learning.
AB  - Motor sequence learning is considered the result of the outflow of information
      following cognitive control processes that are shared by other goal-directed
      behaviours. Emerging evidence suggests that focused-attention meditation (FAM)
      establishes states of enhanced cognitive control, that then exert top-down
      control biases in subsequent unrelated tasks. With respect to sequence learning,
      a single-session of FAM has been shown to entrain stimulus-dependent forms of
      sequential behaviour in meditation naive individuals. In the present experiment,
      we compared single-session effects of FAM and a computerised attention task (CAT)
      to test if FAM-induced enhanced top-down control is generally comparable to
      cognitive tasks that require focused attention. We also investigated if effort,
      arousal or pleasure associated with FAM, or CAT explained the influence of these
      tasks on sequence learning. Relative to a rest-only control condition, both FAM
      and CAT resulted in shorter reaction time (RT) in a serial reaction time task
      (SRTT), and this enhanced RT performance was associated with higher reliance on
      stimulus-based planning as opposed to sequence representation formation. However,
      following FAM, a greater rate of improvement in RT performance was observed in
      comparison to both CAT and control conditions. Neither effort, arousal nor
      pleasure associated with FAM or CAT explained SRTT performance. These findings
      were interpreted to suggest that the effect of FAM states on increased top-down
      control during sequence learning is based on the focused attention control
      feature of this meditation. FAM states might be associated with enhanced
      cognitive control to promote the development of more efficient stimulus-response
      processing in comparison to states induced by other attentional tasks.

PMID- 30240893
TI  - Small Bowel Ulcers From Cryocrystalglobulinemia.

PMID- 30240894
TI  - Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for
      Clinicians.
AB  - Advances in technical capabilities for reading complex human microbiomes are
      leading to an explosion of microbiome research, leading in turn to intense
      interest among clinicians in applying these techniques to their patients. In this
      review, we discuss the content of the human microbiome, including intersubject
      and intrasubject variability, considerations of study design including important
      confounding factors, and different methods in the laboratory and on the computer
      to read the microbiome and its resulting gene products and metabolites. We
      highlight several common pitfalls for clinicians, including the expectation that
      an individual's microbiome will be stable, that diet can induce rapid changes
      that are large compared with the differences among subjects, that everyone has
      essentially the same core stool microbiome, and that different laboratory and
      computational methods will yield essentially the same results. We also highlight
      the current limitations and future promise of these techniques, with the
      expectation that an understanding of these considerations will help accelerate
      the path toward routine clinical application of these techniques developed in
      research settings.

PMID- 30240895
TI  - New concepts in the diagnosis and management of choroidal metastases.
AB  - The most frequent site of ocular metastasis is the choroid. The occurrence of
      choroidal metastases has increased steadily due to the longer survival of
      metastatic patients and the improvement of diagnostic tools. Fundoscopy,
      ultrasonography, and fluorescein angiography are now complemented by indocyanine
      green angiography and optical coherence tomography. Choroidal tumor biopsy may
      also confirm the metastatic nature of the tumor and help to determine the site of
      the primary malignancy. There is currently no consensus on the treatment
      strategy. Most patients have a limited life expectancy and for these complex
      treatments are generally not recommended. However, recent advances in systemic
      therapy have significantly improved survival of certain patients who may benefit
      from an aggressive ocular approach that could preserve vision. Although external
      beam radiation therapy is the most widely used treatment, more advanced forms of
      radiotherapy that are associated with fewer side effects can be proposed in
      select cases. In patients with a shorter life expectancy, systemic therapies such
      as those targeting oncogenic drivers, or immunotherapy can induce a regression of
      the choroidal metastases, and may be sufficient to temporarily decrease visual
      symptoms. However, they often acquire resistance to systemic treatment and ocular
      relapse usually requires radiotherapy for durable control. Less invasive office
      based treatments, such as photodynamic therapy and intravitreal injection of anti
      VEGF, may also help to preserve vision while reducing time spent in medical
      settings for patients in palliative care. The aim of this review is to summarize
      the current knowledge on choroidal metastases, with emphasis on the most recent
      findings in epidemiology, pathogenesis, diagnosis and treatment.

PMID- 30240888
TI  - Comparison of Common Monogenic Defects in a Large Predominantly Antibody
      Deficiency Cohort.
AB  - BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common
      primary immunodeficiencies, characterized by hypogammaglobulinemia and inability
      to generate effective antibody responses. OBJECTIVE: We intended to report most
      common monogenic PADs and to investigate how patients with PAD who were primarily
      diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and
      common variable immunodeficiency (CVID) have different clinical and immunological
      findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were
      performed for confirmation of the mutations in the patients clinically diagnosed
      as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550
      registered patients, the predominant genetic defects associated with
      agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 MU heavy chain
      deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine
      deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like
      anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and
      Facial dysmorphism syndromes) were identified. Clinical disease severity was
      significantly higher in patients with MU heavy chain and CD40 ligand mutations
      compared with patients with BTK (P = .003) and activation-induced cytidine
      deaminase (P = .009) mutations. Paralysis following live polio vaccination was
      considerably higher in patients with MU heavy chain deficiency compared with BTK
      deficiency (P < .001). We found a genotype-phenotype correlation among patients
      with BTK mutations regarding clinical manifestation of meningitis and chronic
      diarrhea. Surprisingly, we noticed that first presentations in most patients with
      Immunodeficiency, Centromeric instability, and Facial dysmorphism were
      respiratory complications (P = .008), whereas first presentations in patients
      with lipopolysaccharides-responsive beige-like anchor deficiency were
      nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights
      similarities and differences in the clinical and genetic spectrum of the most
      common PAD-associated gene defects. This comprehensive comparison will facilitate
      clinical decision making, and improve prognosis and targeted treatment.

PMID- 30240897
TI  - New insights into the development of B cell responses: Implications for solid
      organ transplantation.
AB  - A resurgent interest in the role of B cells following solid organ transplantation
      is being driven by clinical data suggesting that antibody mediated rejection
      (AMR) is a major cause of dysfunction and organ transplant failure. These
      observations suggest that, in a subset of patients, current immunotherapies are
      failing to control the development of alloantibody responses, and/or failing to
      reverse the production or the effects of alloantibodies. Quantification of donor
      specific antibodies (DSA) has proven to be an imperfect predictor of AMR, and
      efforts to improve DSA quantification anticipate that this will result in
      improved predictive power. At the same time, attempts to control of ABMR have
      focused on the non-specific elimination of B cells, plasma cells (PCs) or
      circulating antibodies. In the past decade, there has been an improvement in our
      understanding of the processes that drive B cell differentiation into germinal
      center (GC)-dependent or GC-independent memory B cells and antibody-secreting PC.
      These insights are suggesting new ways to more specifically target the DSA
      response, which may lead to better long-term allograft survival outcomes while
      preserving protective immunity. In this review, new insights into processes that
      lead to antibody production upon primary and secondary antigen encounter are
      discussed, and the potential implications to DSA production as well as future
      areas of investigation to control AMR are discussed.

PMID- 30240896
TI  - Allelic resolution NGS HLA typing of Class I and Class II loci and haplotypes in
      Cape Town, South Africa.
AB  - The development of next-generation sequencing (NGS) methods for HLA genotyping
      has already had an impact on the scope and precision of HLA research. In this
      study, allelic resolution HLA typing was obtained for 402 individuals from Cape
      Town, South Africa. The data were produced by high-throughput NGS sequencing as
      part of a study of T-cell responses to Mycobacterium tuberculosis in
      collaboration with the University of Cape Town and Stanford University. All
      samples were genotyped for 11 HLA loci, namely HLA-A, -B, -C, -DPA1, -DPB1, 
      DQA1, -DQB1, -DRB1, -DRB3, -DRB4, and -DRB5. NGS HLA typing of samples from Cape
      Town inhabitants revealed a unique cohort, including unusual haplotypes, and 22
      novel alleles not previously reported in the IPD-IMGT/HLA Database. Eight novel
      alleles were in Class I loci and 14 were in Class II. There were 62 different
      alleles of HLA-A, 72 of HLA-B, and 47 of HLA-C. Alleles A*23:17, A*43:01,
      A*29:11, A*68:27:01, A*01:23, B*14:01:01, B*15:10:01, B*39:10:01, B*45:07,
      B*82:02:01 and C*08:04:01 were notably more frequent in Cape Town compared to
      other populations reported in the literature. Class II loci had 21 different
      alleles of DPA1, 46 of DPB1, 27 of DQA1, 26 of DQB1, 41 of DRB1, 5 of DRB3, 4 of
      DRB4 and 6 of DRB5. The Cape Town cohort exhibited high degrees of HLA diversity
      and relatively high heterozygosity at most loci. Genetic distances between Cape
      Town and five other sub-Saharan African populations were also calculated and
      compared to European Americans.

PMID- 30240898
TI  - Perioperative Management of Women Undergoing Risk-reducing Surgery for Hereditary
      Breast and Ovarian Cancer.
AB  - Carriers of genetic mutations that predispose to cancer syndromes are often faced
      with complex decisions. For women with hereditary breast and ovarian cancer in
      particular, the decision to undergo risk-reducing mastectomy or bilateral
      salpingo-oophorectomy is burdensome from a physical and psychological
      perspective. Although risk-reducing surgery is the most effective preventative
      measure in reducing a genetic mutation carrier's risk of breast or ovarian
      cancer, the success of these procedures requires a multidisciplinary approach
      that centers on careful counseling regarding the risks and benefits of risk
      reducing surgery. The physical and psychological distress associated with risk
      reducing surgery often makes a combined surgical approach attractive to some
      patients. In this review, we present the evidence surrounding the comprehensive
      surgical care of women with hereditary breast and ovarian cancer syndromes and
      evaluate the perioperative factors that influence surgical management.

PMID- 30240899
TI  - When Less Is More: Minimally Invasive Surgery Compared with Laparotomy for
      Interval Debulking After Neoadjuvant Chemotherapy in Women with Advanced Ovarian
      Cancer.
AB  - STUDY OBJECTIVE: To compare outcomes of advanced ovarian cancer patients who had
      minimally invasive surgery (MIS) with outcomes of advanced ovarian cancer
      patients who had laparotomy for interval cytoreduction after neoadjuvant
      chemotherapy (NACT). DESIGN: Retrospective cohort study (Canadian Task Force
      classification II-2). SETTING: One large teaching hospital with a tertiary
      referral function for gynecologic oncology and MIS. PATIENTS: All consecutive
      patients with stages III to IV epithelial ovarian, tubal, or peritoneal cancer
      who underwent MIS or laparotomy for interval cytoreduction after at least 1 NACT
      cycle from 2006 to 2017 at 1 institution. INTERVENTIONS: Patients underwent
      either MIS or laparotomy for interval cytoreduction after at least 1 cycle of
      NACT. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed and data
      abstracted and analyzed. Survival was estimated by the Kaplan-Meier method, and
      outcomes were compared with Fisher's exact test, Student's t test, Wilcoxon rank
      sum test, and the log-rank test. In total, 157 assessable patients underwent
      interval cytoreductive surgery through MIS (n = 53) or laparotomy (n = 104). MIS
      was completed without conversion in 44 of 53 patients (83%), of whom 20 required
      a hand port and/or mini-laparotomy. R-zero and optimal resections were achieved
      in 60.4% and 96.3% of MIS patients respectively, compared with 42.3% and 82.7% of
      laparotomy patients (p = .02). MIS patients had lower estimated blood loss (EBL;
      156 vs 278 mL, p <.001), fewer intraoperative transfusions (2% vs 17%, p = .006),
      and shorter hospital stay (3.0 vs 5.7 days, p < .001). Operative time was longer
      (171 vs 150 minutes, p = .007), but complications, intensive care unit stay,
      readmission, median progression-free survival (27 vs 29 months, p = .45), and
      median overall survival (37 vs 35 months, p = .74) were similar. CONCLUSION: MIS
      is feasible and effective for interval cytoreduction after NACT in advanced
      ovarian cancer patients. MIS is associated with less EBL, lower transfusion rate,
      and shorter length of hospital stay with no difference in patient outcomes.

PMID- 30240900
TI  - Techniques for Preemptive Analgesia in Gynecologic Surgery.
AB  - STUDY OBJECTIVE: To provide surgeons with techniques for preemptive analgesia
      during minimally invasive gynecologic surgery. DESIGN: Instructional video
      demonstrating variety of preemptive analgesia techniques and the corresponding
      neuroanatomy (Canadian Task Force Classification III). SETTING: Postoperative
      pain management is an important component of patient care after gynecologic
      surgery. There have been numerous advances in pain management, including studies
      which show that preoperative administration of analgesics decreases postoperative
      pain scores and narcotic medication requirements.[1-3] However, there is limited
      information on the techniques for preemptive analgesia.[4,5] Mayo Clinic
      Institutional Review Board approval was not required for this video article.
      INTERVENTION: Relevant abdominopelvic neuroanatomy is reviewed. This is followed
      by demonstration of preemptive analgesia techniques based on neuroanatomy
      principles. CONCLUSION: Techniques for preemptive analgesia are simple and
      effective. These tools can be utilized for patients undergoing gynecological
      surgeries via a vaginal or abdominal approach and can help optimize postoperative
      pain and narcotic usage.

PMID- 30240901
TI  - Discharge Readiness after Robotic and Laparoscopic Hysterectomy.
AB  - STUDY OBJECTIVE: To evaluate which factors may be predictive of patient readiness
      of discharge after robotic and laparoscopic hysterectomy. DESIGN: A prospective
      cohort study (Canadian Task Force classification II-2). SETTING: A single
      tertiary care center in the United States. PATIENTS: All 230 patients undergoing
      robotic and laparoscopic hysterectomy between November 2015 and April 2017.
      INTERVENTIONS: The primary outcome measure was whether or not the patient felt
      ready for discharge when she was sent home, and this was assessed using a survey
      4 to 6 weeks after surgery. Secondary outcomes included the number of
      postoperative phone calls, 30-day readmission, and also whether the patient felt
      knowledgeable about postoperative symptoms and restrictions (both assessed via a
      4- to 6-week survey). Associations of baseline, operative, and postoperative
      characteristics with outcomes were evaluated using regression models appropriate
      for the nature of the given outcome measure. MEASUREMENTS AND MAIN RESULTS: Of
      the 230 patients, 207 (90%) reported they felt ready for discharge on the
      postoperative survey. The majority of patients strongly agreed that they felt
      knowledgeable about what symptoms to expect postoperatively (60%) and about
      postoperative restrictions (71%). The median number of postoperative phone calls
      was 1 (range, 0-11), with 104 patients (45%) having more than 1 postoperative
      call. The only factor that was significantly associated with a lack of readiness
      for discharge was a longer total operating room time (p = .011). Factors
      associated with more postoperative phone calls were a urogynecologic indication
      (p = .005), a cancer indication (p = .024), a longer total operative room time (p
      = .014), a postoperative complication (p <.001), and not seeing a patient
      education video (p = .018). Knowledge of postoperative restrictions was
      significantly worse for older patients (p = .004) and varied significantly
      according to surgeon (p = .038). No significant predictors of knowledge of
      postoperative symptoms were identified. CONCLUSIONS: Discharge readiness and
      knowledge of postoperative restrictions and symptoms were high in patients who
      underwent laparoscopic and robotic hysterectomies. The risk factors for outcomes
      that were identified highlight groups of patients who can be targeted for
      preemptive interventions both preoperatively and postoperatively.

PMID- 30240902
TI  - Grouped sparse Bayesian learning for voxel selection in multivoxel pattern
      analysis of fMRI data.
AB  - Multivoxel pattern analysis (MVPA) methods have been widely applied in recent
      years to classify human brain states in functional magnetic resonance imaging
      (fMRI) data analysis. Voxel selection plays an important role in MVPA studies not
      only because it can improve decoding accuracy but also because it is useful for
      understanding brain functions. There are many voxel selection methods that have
      been proposed in fMRI literature. However, most of these methods either overlook
      the structure information of fMRI data or require additional cross-validation
      procedures to determine the hyperparameters of the models. In the present work,
      we proposed a voxel selection method for binary brain decoding called group
      sparse Bayesian logistic regression (GSBLR). This method utilizes the group
      sparse property of fMRI data by using a grouped automatic relevance determination
      (GARD) as a prior for model parameters. All the parameters in the GSBLR can be
      estimated automatically, thereby avoiding additional cross-validation.
      Experimental results based on two publicly available fMRI datasets and simulated
      datasets demonstrate that GSBLR achieved better classification accuracies and
      yielded more stable solutions than several state-of-the-art methods.

PMID- 30240903
TI  - Early breast milk exposure modifies brain connectivity in preterm infants.
AB  - Preterm infants are at increased risk of alterations in brain structure and
      connectivity, and subsequent neurocognitive impairment. Breast milk may be more
      advantageous than formula feed for promoting brain development in infants born at
      term, but uncertainties remain about its effect on preterm brain development and
      the optimal nutritional regimen for preterm infants. We test the hypothesis that
      breast milk exposure is associated with improved markers of brain development and
      connectivity in preterm infants at term equivalent age. We collected information
      about neonatal breast milk exposure and brain MRI at term equivalent age from 47
      preterm infants (mean postmenstrual age [PMA] 29.43 weeks, range 23.28-33.0).
      Network-Based Statistics (NBS), Tract-based Spatial Statistics (TBSS) and
      volumetric analysis were used to investigate the effect of breast milk exposure
      on white matter water diffusion parameters, tissue volumes, and the structural
      connectome. Twenty-seven infants received exclusive breast milk feeds for >=75%
      of days of in-patient care and this was associated with higher connectivity in
      the fractional anisotropy (FA)-weighted connectome compared with the group who
      had < 75% of days receiving exclusive breast milk feeds (NBS, p = 0.04). Within
      the TBSS white matter skeleton, the group that received >=75% exclusive breast
      milk days exhibited higher FA within the corpus callosum, cingulum cingulate
      gyri, centrum semiovale, corticospinal tracts, arcuate fasciculi and posterior
      limbs of the internal capsule compared with the low exposure group after
      adjustment for PMA at birth, PMA at image acquisition, bronchopulmonary
      dysplasia, and chorioamnionitis (p < 0.05). The effect on structural connectivity
      and tract water diffusion parameters was greater with >=90% exposure, suggesting
      a dose effect. There were no significant groupwise differences in brain volumes.
      Breast milk feeding in the weeks after preterm birth is associated with improved
      structural connectivity of developing networks and greater FA in major white
      matter fasciculi.

PMID- 30240904
TI  - Exploring Alzheimer's disease mouse brain through X-ray phase contrast
      tomography: From the cell to the organ.
AB  - Alzheimer's disease (AD), the most common form of dementia, is a progressive
      neurodegenerative disorder associated with aberrant production of beta-amyloid
      (Abeta) peptide depositing in brain as amyloid plaques. While animal models allow
      investigation of disease progression and therapeutic efficacy, technology to
      fully dissect the pathological mechanisms of this complex disease at cellular and
      vascular levels is lacking. X-ray phase contrast tomography (XPCT) is an advanced
      non-destructive 3D multi-scale direct imaging from the cell through to the whole
      brain, with exceptional spatial and contrast resolution. We exploit XPCT to
      simultaneously analyse disease-relevant vascular and neuronal networks in AD
      mouse brain, without sectioning and staining. The findings clearly show the
      different typologies and internal structures of Abeta plaques, together with
      their interaction with patho/physiological cellular and neuro-vascular
      microenvironment. XPCT enables for the first time a detailed visualization of
      amyloid-angiopathy at capillary level, which is impossible to achieve with other
      approaches. XPCT emerges as added-value technology to explore AD mouse brain as a
      whole, preserving tissue chemistry and structure, enabling the comparison of
      physiological vs. pathological states at the level of crucial disease targets. In
      vivo translation will permit to monitor emerging therapeutic approaches and
      possibly shed new light on pathological mechanisms of neurodegenerative diseases.

PMID- 30240905
TI  - Is muscle strength in a painful limb affected by knee pain status of the
      contralateral limb? - Data from the Osteoarthritis Initiative.
AB  - Contralateral knee pain has been suggested to be associated with muscle weakness
      in a pain-free knee, potentially through a mechanism of central nervous
      inhibition. Whether contralateral knee pain also affects muscle strength in a
      painful knee, however, is unknown. Here we study the extent to which isometric
      muscle strength differs between matched painful limbs of people with unilateral
      knee pain vs. matched painful limbs people with bilateral knee pain. To that end,
      163 participants with unilateral knee pain were identified from the
      Osteoarthritis Initiative. Unilaterally painful (UP) limbs were defined as having
      numerical rating scale (NRS) >=4/10, infrequent/frequent pain in the painful
      limb, while contralateral pain-free limbs were defined by NRS=0-1, no/infrequent
      pain and Western Ontario and McMaster Universities Arthritis Index (WOMAC) <=1.
      The comparator group were matched bilaterally painful (BP) limbs. Maximum
      isometric muscle strength (N) was compared between 1:1 matched BP and UP limbs.
      Extensor strength was found to be lower in BP limbs than in UP limbs, (-2.9%;
      p=0.39) but this difference was not statistically significant. Extensor strength
      was significantly lower in the UP vs. contralateral pain-free limbs (-6.2%;
      p<0.001). No differences were observed between BP and contralateral painful limbs
      (0.6%; p=0.87). In conclusion, the current results identify a slight reduction of
      maximum knee extensor strength in a painful limb, when the contralateral knee is
      also painful. In contrast to pain-free limbs, this effect did not reach
      statistical significance, but the overall findings support the concept of central
      nervous inhibition of muscle strength by contralateral knee pain.

PMID- 30240906
TI  - Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat
      model of the andropause.
AB  - In a rat model of the andropause we aimed to examine the influence of daidzein,
      soy isoflavone, on the structure and function of parathyroid glands (PTG) and the
      expression levels of some of the crucial regulators of Ca2+ and Pi homeostasis in
      the kidney, and to compare these effects with the effects of estradiol, serving
      as a positive control. Middle-aged (16-month-old) male Wistar rats were divided
      into the following groups: sham-operated (SO), orchidectomized (Orx),
      orchidectomized and estradiol-treated (Orx+E; 0.625mg/kg b.w./day, s.c.) as well
      as orchidectomized and daidzein-treated (Orx+D; 30mg/kg b.w./day, s.c.) group.
      Every treated group had a corresponding control group. PTH serum concentration
      was decreased in Orx+E and Orx+D groups by 10% and 21% (p<0.05) respectively, in
      comparison with the Orx. PTG volume was decreased in Orx+E group by 16% (p<0.05),
      when compared to the Orx. In Orx+E group expression of NaPi 2a was lower
      (p<0.05), while NaPi 2a abundance in Orx+D animals was increased (p<0.05), when
      compared to Orx. Expression of PTH1R was increased (p<0.05) in Orx+E group, while
      in Orx+D animals the same parameter was decreased (p<0.05), in comparison with
      Orx. Klotho expression was elevated (p<0.05) in Orx+D rats, in regard to Orx.
      Orx+D induced reduction in Ca2+/creatinine and Pi/creatinine ratio in urine by
      32% and 16% (p<0.05) respectively, in comparison with Orx. In conclusion,
      presented results indicate the more coherent beneficial effects of daidzein
      compared to estradiol, on disturbed Ca2+ and Pi homeostasis, and presumably on
      bone health, in the aging male rats.

PMID- 30240907
TI  - Lymphatic vessels of the eye - old questions - new insights.
AB  - Due to its accessible position and tissue heterogeneity, the eye is ideally
      suited for studying the lymphatic system. As early as the 19th century, questions
      about the origin and function of this system were discussed. For example, whether
      Schlemm's canal, which is of particular importance in the pathogenesis of
      glaucoma, is a lymphatic vessel, or does this vascular system begin with finger
      shaped protuberances? Despite the discovery of lymphatic endothelial molecules
      and the use of molecular imaging technologies, these questions are still
      discussed controversially today. Leber demonstrated in 1873 with a solution
      consisting of two dyes of different particle size that only the smaller particles
      from the anterior chamber of the eye filled the episcleral and conjunctival veins
      around the corneal margin. He believed to have proven - to be read in the
      historical review of our article - that the Canalis Schlemmii in humans is a
      venous circular vessel and not a lymphatic vessel. In our own investigations, we
      reduced the rather contradictory and complex question of whether there are
      lymphatic vessels in the eye to the question of whether there are drainage
      connections between the different sections of the eye and the lymphatic system or
      not. With different radioactive tracers and combined with unilateral ligation of
      cervical lymph vessels, we observed outflow from the subconjunctival and
      retrobulbar space, from the anterior chamber and the vitreous body. The rate of
      discharge of the radioactive tracer was determined by the radiopharmaceutical and
      injection site. In analogy to the lymphatic drainage of the head we found a
      segmental drainage of lymphatic substances on the eye. Vitreous humour and
      retrobulbar space were drained by lymphatic vessels, predominantly to the deep
      cervical lymph nodes, while anterior chamber and subconjunctival space drains
      predominated over the superficial cervical lymph nodes. Eyeball tattoos - as
      loved by some fan communities - should therefore cause a coloured staining of the
      superficial cervical lymph nodes. The boundary of the drained segments would be
      in the area of the eyeball's equator. According to the textbooks, the lymph is
      actively removed from finger-shaped initial segments via pre-collectors and
      collectors with properly functioning intraluminal valves and smooth muscle cells
      in the vessels' media. In patients with spontaneous conjunctival bleeding,
      however, we observed phenomena in the conjunctival lymph vessels, which ca not be
      explained with old familiar ideas. At nozzle-shaped vessel constrictions
      separation of blood components occurred. The erythrocytes formed partially a so
      called fluidic "resting bulk layer". Parallel vessel parts caused a retrograde
      filling of already emptied segments. These observations led our experimental
      investigations. In the literature, there are different scanning electron
      microscopy (SEM) images of lymphatic endothelial surfaces; nevertheless they are
      unassigned to a particular vessel segment. In the conjunctiva, we studied the
      question whether there is a dependence between vessel diameter and the surface
      characteristics of endothelial cells (after unfolding by lymphography). A
      constantly applied photo-mathematical procedure for all specimens allowed
      determining the size of the cross sections. The specimens were randomized into
      seven groups with diameters of 0.1-1.0mm and above and examined by SEM. In the
      smallest vessels (diameter=0.11mm), the impressions of the occasionally occurring
      nuclei in the lumen were clearly impressive. With increasing diameter, these
      impressions were lost and the individual endothelial nuclei could no longer be
      identified. Rather, one recognized only wall-like structures. In vessels of
      intermediate diameter (0.3-0.4mm), structures could be seen on the surface
      similar to reticular fibres. With increasing diameters, their prominent character
      weakened. In the group with diameters above 0.5mm, wavy surface structures were
      shown. Finally, in vessels of diameters over 1.0mm, a uniform, flat surface was
      observed. Regardless of the collection site of the specimens, we found certain
      surface characteristics related to the vessels' calibre. In further
      investigations by means of interstitial dye lymphography, we were able to
      demonstrate in the conjunctiva that under increasing injection pressure,
      additional vessels stained from finger-shaped processes. At least in the
      conjunctiva, the existence of so-called "blind-ending initial segments" seems
      doubtful (despite the fact that initial segments or "initial lymphatics" would
      begin in periphery, not end). Rather, these are likely to be temporary filling
      states. SEM investigations were carried out on the internal structure of these
      dome-shaped vessel parts by means of a specially developed preparation technique.
      Despite numerous variants in the lymphographic design of the blind bags - in the
      form of finger, balloon, dome, piston, pyramidal, double-humped and spearhead
      like endings - slot-shaped, lip-shaped and saw blade-like structures were
      repeatedly found, similar to a zipper. These findings suggest preformed
      connections to the next segment and may control lymphatic flow. To clarify the
      retrograde fluid movements, we examined the lymph vessels' valves or those
      structures that were previously interpreted as valves. The different structures
      found could be subdivided into three groups. The lack of common bicuspid
      structures provides an explanation for retrograde fluid movement. That
      nevertheless a directional flow is possible, is explained by the flow model
      developed by Gerhart Liebau. Conjunctival lymphatics show intraluminal structures
      by double contrast injection, which we divided into four groups due to anatomical
      differences: An accurate statement about the occurrence of certain intraluminal
      vascular structures in certain vascular calibres was possible only conditionally.
      However, complex and extended structures (group d) were found almost exclusively
      in larger vessel calibres (diameter>0.9mm). The structures are reminiscent of
      published findings in the "collector channel orifices of Schlemm's canal". They
      should play an important role in the regulation of the intraocular pressure, or
      the balance between production and outflow of the aqueous humour. The influence
      of such structures on the function of the lymphatic vessels is not yet known. As
      an approach models could be used, which for instance are applied in the water
      industry for the drainage, the degradation of introduced substances, or the
      detention pond. The latter serves for the retention and purification of drainage
      water (storage, treatment and reuse of drainage water). Dead zones, barriers,
      short-circuit currents and swirling are further hydraulic terms. Can intraluminal
      vascular structures, for example, affect the lymphatic flow and thus the mechano
      sensitivity of lymphatic endothelial cells? Whatever interpretation model we use,
      the warning of the Swiss anatomist His from 1862 is still true today that all
      theories about the formation and movement of lymph should be based on precise
      anatomical basics. This review article therefore tries to make a contribution
      therefore. Despite knowing of lymphatic endothelial molecules, despite the
      discovery of the role of lymphangiogenic growth factors in diseases and the use
      of molecular imaging technologies, we still know too little about the anatomy and
      function of the lymphatic system.

PMID- 30240908
TI  - The differences in the structure of the motor nucleus of the medial gastrocnemius
      muscle in male and female rats.
AB  - There are many reports describing sexual dissimilarities in the CNS, particularly
      in the brain and cortical regions. However, knowledge regarding sexual
      dissimilarities in the spinal cord and in particular in the hindlimb muscle
      motoneuron connectivity controlling locomotion is limited. In order to recognise
      sex differences in the architecture of the medial gastrocnemius (MG) motor
      nucleus in rats of the same age, retrograde-labelled motoneurons were identified
      following a bath of the proximal stump of the transected MG nerve in horseradish
      peroxidase. The rostrocaudal distribution of motoneurons along the spinal cord
      and on transverse sections as well as the size and density of motoneurons in the
      motor nucleus were determined from serial microscopic images. It was shown that
      the MG pool extended throughout the L4-L6 segments, with a length that was 32%
      greater in males. The position of the moto pool within the ventral horn of the
      spinal cord transversal sections was also different in both sexes: the pool was
      located more dorsally and laterally in males. Three size categories of
      motoneurons with different soma diameters were distinguished: alpha1 (27.5
      40.0MUm), alpha2 (>40.0MUm) and gamma (<27.5MUm). The density of alpha (alpha1
      and alpha2) motoneurons as well as gamma motoneurons was higher in females, by
      about 13% and 23%, respectively. The number of alpha1 motoneurons was 8% higher
      in females, whereas there were 46% more alpha2 motoneurons in males. The most
      significant differences in the distribution concerned alpha2 motoneurons, which
      revealed a lower density in the rostral parts of the MG motor nucleus in females.
      It was therefore concluded that the length of the MG motor nucleus was shorter,
      whereas the mean density of alpha and gamma motoneurons was higher in females.

PMID- 30240909
TI  - Distribution of the neuropeptide calcitonin gene-related peptide-alpha of tooth
      germ during formation of the mouse mandible.
AB  - Calcitonin gene-related peptide-alpha (CGRPalpha) is a neurotransmitter that is
      related to bone formation during development. However, CGRP expression is not
      well known to affect the formation of teeth during development. During tooth germ
      development, the relationships among CGRPalpha, calcitonin receptor-like receptor
      (CRLR), amelogenin (AMELX), dentin sialophosphoprotein (DSPP), osteopontin (OPN)
      and osteocalcin (OCN) are unclear despite various tooth and osteogenesis markers.
      Our real-time RT-PCR results showed that the expression levels of CGRPalpha mRNA
      gradually decreased, in contrast to the mRNA abundances of CRLR, AMELX, DSPP,
      OPN, and OCN, which rapidly increased from E14.5 to P1 in the mandible. In situ
      hybridization using an antisense probe for CGRPalpha mRNA showed significant
      localized expression levels around the tooth bud at E14.5 and epithelial cells
      near the dental ledge and outer and inner enamel epithelium at E17.5 compared to
      those at P1. The localization of the anti-CGRPalpha antibody reaction revealed a
      strong positive reaction at the surface layer of oral epithelial cells at E14.5
      and oral epithelial cells of the dental lamina around the dental ledge depression
      in the mandible of E17.5 mice using immunohistochemical methods The different
      anti-CGRPalpha reaction revealed its important roles during tooth formation at
      the postnatal stage. CGRPalpha mRNA was also detected in the interactions of
      tooth germ with the formation of odontoblast and amelobast layers from dental
      papilla and inner enamel epithelium. CGRPalpha may also be related to tooth germ
      development. Furthermore, CGRPalpha is an important tooth and bone formation
      marker, and bone cells provide further evidence of a role in mandibular
      development in contrast to inflammatory systems.

PMID- 30240910
TI  - Calpain2 but not calpain1 mediated by calpastatin following glutamate-induced
      regulated necrosis in rat retinal neurons.
AB  - The purpose of this study is to investigate whether calpastatin (CAST) plays an
      important role in the regulated necrosis (RN) in rat retinal neurons under an
      excessive glutamate condition and furthermore to investigate whether this process
      is regulated by calapin1 and calpain2. In the present study, glutamate triggered
      CAST inhibition, calpain2 activation and retinal neuronal RN after injury. The
      application of CAST active peptide could provide protective effects against
      activated calpain2 mediated RN. However, the calpain1 activity was not changed in
      these processes. Finally, in vivo studies further confirmed the role of the CAST
      calpain2 pathway in cellular RN in the rat retinal ganglion cell layer and inner
      nuclear layer after glutamate excitation. In addition, flash electroretinogram
      results provided evidence that the impaired visual function induced by glutamate
      could recover after CAST peptide treatment. This research indicated that
      excessive glutamate may lead to CAST inhibition and activated calpain2, but not
      calpain1 activation, resulting in RN.

PMID- 30240911
TI  - Differentiation of eye field neuroectoderm from human adipose-derived stem cells
      by using small-molecules and hADSC-conditioned medium.
AB  - Recently, stem-cell therapy as a promising therapeutic alternative is considered
      to treat retinal degenerative diseases. Here, we used small molecules and
      concentrated conditioned medium selectively enriched with Amicon filter units
      from human adipose-derived stem cells (hADSC-CM) containing various neurotrophic
      factors to induce hADSCs toward eye field neuroectoderm (EFN). For induction of
      stem cells, hADSC-CM and small molecules CKI-7, SB431542 and LDN193189 as
      inhibitors of Wnt, Nodal and BMP4 signaling pathways were used, respectively. We
      found the highest expression of beta-TUB III as a neural marker in the group in
      which small molecules and conditioned medium were applied simultaneously.
      Moreover, EFN markers SIX3, PAX6 and RAX had higher expression in the presence of
      a conditioned medium. However, the superior expression of ENF marker OTX2 was
      seen in the small molecules group. Our results indicated that neurotrophic
      factors present in hADSCs-CM could induce hADSCs into EFN cells. Therefore, a
      more thorough study of these factors and their effects in hADSC-CM might pave the
      way for cellular and non-cellular therapy in retinal degenerative diseases.

PMID- 30240912
TI  - The effect of Hengduan Mountains Region (HMR) uplift to environmental changes in
      the HMR and its eastern adjacent area: Tracing the evolutionary history of Allium
      section Sikkimensia (Amaryllidaceae).
AB  - Exploring the effects of orographic events and climatic shifts on geographic
      distribution of organism in the Hengduan Mountains Region (HMR) and its eastern
      adjacent area is crucial to the understanding of the environmental changes to
      organismal evolution. To gain further insight into these processes, we
      reconstruct evolutionary history of ten species in Allium section Sikkimensia,
      distributed across regions abovementioned. Using chloroplast and nuclear sequence
      variation of 79 populations of these ten Allium species with known morphological
      preferences, we elucidate the phylogenetic relationship, divergence time,
      ancestral area and genetic structures. Climatic variables analysis, Isolation by
      distance (IBD) and environment (IBE) and Species distribution modeling (SDM) were
      analyzed along different genetic clades. These analyses indicated that the
      initial split of Sikkimensia was triggered by climate changes following Qinghai
      Tibet Plateau sensu lato (QTPsl) uplift during the late Miocene. Subsequently,
      divergences within lineage (lineage A)/among lineages (lineage C and D) in
      Sikkimensia may be induced by the intense uplift of the HMR around 3-4 Ma and
      abrupt intensifying of the Asian monsoon regimes. Furthermore, Sikkimensia
      populations exhibited lopsided demographic history in the Last Glacial Maximum
      (LGM), as was indicated by the expansion of their range in the QDM and
      contraction in the HMR. Our findings appear to suggest that the HMR uplift could
      have strengthened the orographic difference between the HMR and its eastern
      adjacent area and led to a colder climate in the HMR, while geological topography
      also played an important role for taxa to respond the climate change that had
      taken place in the HMR and its eastern adjacent area during the Pleistocene.

PMID- 30240913
TI  - Expressed emotion and impulsiveness in mothers of children with Fragile X
      Syndrome and Down Syndrome: The relation to behavioral problems in their
      offspring.
AB  - BACKGROUND: Fragile X Syndrome (FXS) and Down Syndrome (DS) are common causes of
      Intellectual Disability (ID). Mothers of individuals with FXS sometimes have the
      premutation condition which makes them display neurocognitive signs, such as
      impulsiveness impairments, while mothers of DS individuals, as a group, do not
      have impairments. Although behavior problems in individuals with ID may be
      related to high Expressed Emotion (EE) in parents, parenting in families with ID
      members has been little explored. AIM: To explore the relationship between a
      mother's EE and impulsiveness, in mothers of individuals with FXS and DS, with
      behavior problems in their offspring. METHOD: A questionnaire was developed to
      collect data about impulsiveness and EE in mothers, along with information about
      behavior problems in ID individuals. RESULTS: EE scores were associated with
      behavior problems in their offspring for both samples. Mothers with the
      premutation showed higher scores in EE than mothers of DS individuals. However,
      impulsiveness scores were not different between both parental groups, and were
      related to EE scores. CONCLUSIONS: EE is a parental feature that is possible to
      modulate and seems to be related to behavior problems in ID individuals. More
      research should be carried on to create interventions to reduce this attitude in
      parents of ID individuals.

PMID- 30240914
TI  - Microbial risk assessment in recreational freshwaters from southern Brazil.
AB  - In this study, total coliforms (TC), Escherichia coli, enterovirus (EV),
      rotavirus (RV), and human mastadenovirus species C and F (HAdV-C and HAdV-F) were
      evaluated in water samples from Belo Stream. For HAdV-C and F, the infectivity
      was assessed by integrated cell culture quantitative real-time polymerase chain
      reaction (ICC-qPCR). Samples were collected monthly (May/2015 to April/2016) at
      four sites. Viral analyses were performed for both ultracentrifuge-concentrated
      and unconcentrated samples. For site P4 (used for recreational purposes), QMRA
      was applied to estimate health risks associated with exposure to E. coli and HAdV
      C and F. TC and E. coli were present throughout the collection period. EV and RV
      were not detected. HAdV-C were present in 8.51% (1.89E + 06 to 2.28E + 07 GC
      (Genomic Copies)/L) and 21.27% (2.36E + 05 to 1.29E + 07 GC/L) for unconcentrated
      and concentrated samples, respectively. For HAdV-F were 12.76% (2.77E + 07 to
      3.31E + 08 GC/L) and 48.93% (1.10E + 05 to 4.50E + 08 GC/L) for unconcentrated
      and concentrated samples, respectively. For unconcentrated samples, infectivity
      for HAdV-C was detected in 37.20% (1st ICC-qPCR) and 25.58% (2nd ICC-qPCR). For
      HAdV-F, infectivity was detected in 6.97% (1st ICC-qPCR) and 6.97% (2nd ICC
      qPCR). For concentrated samples, HAdV-C infectious was observed in 17.02% (1st
      ICC-qPCR) and in 8.51% (2nd ICC-qPCR). For HAdV-F, were present in 8.51% for both
      1st and 2nd ICC-qPCR. Statistical analyzes showed significant difference between
      the collection sites when analyzed the molecular data of HAdV-F, data of TC and
      E. coli. Correlation tests showed direct correlation between HAdV-F with E. coli
      and TC. E. coli concentrations translated to the lowest estimates of infection
      risks (8.58E-05 to 2.17E-03). HAdV-F concentrations were associated with the
      highest infection risks at 9.99E-01 and for group C, 1.29E-01 to 9.99E-01. These
      results show that commonly used bacterial indicators for water quality may not
      infer health risks associated with viruses in recreational freshwaters.

PMID- 30240915
TI  - Developing interpretive structural modeling based on factor analysis for the
      water-energy-food nexus conundrum.
AB  - Factor identification and analysis are effective ways to explain and quantify
      complex relationships in the water-energy-food nexus (WEF-nexus). It has been
      acknowledged that factors in the WEF-nexus vary by time, level and location, but
      the hierarchy between factors has been largely ignored. Taking advantage of the
      interpretive structural modeling (ISM) method, this paper presents an
      identification and analysis on the interwoven factors in an urban WEF-nexus in
      Beijing. As a result, 87 representative factors have been identified and
      classified, with a hierarchy structure established by ISM. Based on the relative
      importance of given factors, factor hierarchy structure shows that the energy
      system in the core nexus is the essential system and is critical to promoting the
      WEF-nexus in Beijing; factors from peripheral nexuses - such as population and
      vehicle volume - also have a significant influence on nexus governance.
      Furthermore, integrated policies from subsystems within the core nexus or between
      the core and peripheral nexuses are critical to secure WEF in Beijing. Factor
      analysis suggests that the portrayed nexus structure could provide valuable
      references for further quantification and decision making.

PMID- 30240916
TI  - Assessment of metal contamination in water and sediments from major rivers in
      South Korea from 2008 to 2015.
AB  - This study is the first report to evaluate (8 years data) the contamination
      degree and distribution characteristics of metals in the surface water and
      sediments of four Korean rivers (Nakdong, Yeongsan, Geum, and Han). Eight years
      of data were evaluated, and metal concentrations in the river water were found to
      be below permissible limits but high enough to cause detrimental effects (under
      chronic exposure) to aquatic organisms. The analysis of metals in the river
      sediments showed the following trend: Zn > Cu > Cd > Pb > Ni > As > Cr > Hg. The
      concentrations of metals in sediments (especially in the Geum and Han rivers)
      were above the permissible limits reported by international agencies.
      Concentrations of Cu, Ni, and Zn were high enough to pose risks to aquatic
      communities. In sediments, metals pollution was also evaluated using different
      indices, such as enrichment factor (EF), geoaccumulation index (Igeo),
      contamination factor (CF), degree of contamination (Cd), modified degree of
      contamination (mCd), and pollution load index (PLI). The CF, EF, and Igeo indices
      demonstrated that most of the river sediment samples were moderately to heavily
      contaminated by Cd, Cu, Pb, and Zn. The PLI values were above one in the Geum and
      Han river sediments, which indicated polluted conditions. Similarly, Cd indicated
      a considerable to very high degree of contamination, while mCd indicated a low to
      moderate degree of contamination in all four river sediments. Finally, it was
      found that the extent of metals pollution in the Korean rivers reached a critical
      condition, which could be detrimental to the biota of the rivers, as well as to
      humans in the long term.

PMID- 30240917
TI  - Arbuscular mycorrhizal fungi and sewage sludge enhance growth and adaptation of
      Metrosideros laurifolia on ultramafic soil in New Caledonia: A field experiment.
AB  - The ecological restauration of nickel mining-degraded areas in New Caledonia is
      strongly limited by soil mineral nutrient deficiencies, heavy metal toxicity and
      slow growth rate of the native plant species. The improvement of revegetation
      technics needs multidisciplinary knowledge. A field experiment with relocated
      topsoil was assessed to test plant inoculation with a mix of three selected
      arbuscular mycorrhizal fungi (AMF) combined with sewage sludge amendment of the
      soil. Metrosideros laurifolia seedlings, an endemic Myrtaceae, were inoculated
      with the mixed AMF isolates and grown in a nursery for 18 months before being
      planted. 528 days after plantation, the dry weight of inoculated plants was 4
      times higher than non-inoculated ones. AMF inoculated plants growing in sewage
      sludge amended soil showed a dry weight more than seven times higher than control
      plants. These differences were positively correlated with mycorrhizal
      colonization. However at this stage, AMF inoculated isolates were reduced in
      roots of M. laurifolia and replaced by several AMF indigenous species. This AMF
      diversity was higher in inoculated plants and in non-amended plots. Inoculated
      plants were characterized by a better mineral nutrition, a higher Ca/Mg ratio and
      a lower heavy metal translocation. In conclusion, this study showed that AMF
      inoculation combined with sewage sludge amendment of soil can improve ecological
      restoration of ultramafic mine-degraded areas.

PMID- 30240918
TI  - Source apportionment and source-to-sink transport of major and trace elements in
      coastal sediments: Combining positive matrix factorization and sediment trend
      analysis.
AB  - Major and trace elemental concentrations in coastal marine sediments were
      incorporated into positive matrix factorization (PMF) to identify potential
      sources and source contributions. Transport pathways of fine-grained sediments
      and sediment-bound elements were inferred from sediment trend analysis (STA). The
      spatial distribution patterns of 21 elements (Co, Cu, Ni, Sr, Zn, V, Ba, Sc, Ga,
      Pb, Cr, Zr, SiO2, Al2O3, Fe2O3, MgO, CaO, K2O, MnO, TiO2, and P2O5) coupled with
      sediment grain sizes were investigated. The natural and anthropogenic sources of
      the elements were distinguished by their medium enrichment factors (EFs). Seven
      sources were recognized by PMF: weathering products, anthropologic emissions,
      sand, older sediment, biogenic carbonates, products of siliceous organisms, and
      mine exploitation. Some land-derived elements, including weathering products,
      anthropogenic-related elements, and mining-related elements, had a significant
      positive correlation with sediment silt, clay, and organic carbon contents. The
      spatial patterns of the land-derived elements' concentrations and source
      contributions were consistent with the sediment transport pathways inferred from
      the STA. This result revealed that the delivery of the land-derived elements was
      determined by marine current flows and the associated sediment transport
      processes. Conversely, elements originating from marine sources, such as sand and
      older sediment, and from the biological activities of calcareous and siliceous
      organisms showed little response to sediment transport and deposition processes.
      Our study links the outputs of statistically oriented approaches (e.g., PMF) to a
      process-based understanding of elemental transport in marine environments.

PMID- 30240919
TI  - Flow regimes filter species traits of benthic diatom communities and modify the
      functional features of lowland streams - a nationwide scale study.
AB  - Changes in land use, climate and flow diversion are key drivers of river flow
      regime change that may eventually affect freshwater biodiversity and ecosystem
      functions. However, our knowledge is limited on how the functional features of
      stream organisms vary along the gradient of hydrological disturbance (i.e. flow
      regime changes) and how flow regimes mediate the functional features in lowland
      streams. We analyzed the functional traits of benthic diatoms (unicellular
      siliceous algae) that are most sensitive and tolerant to flow regime changes
      along a nationwide scale of 246 sites in Denmark. We combined RLQ and fourth
      corner analyses to explore the co-variation between hydrological variables (R
      table) and species traits (Q table), constrained by the relative abundance of
      each species (L table) as observed in each of the sampling sites. Further, we
      examine the relationships between functional features (i.e., functional
      redundancy and diversity) and hydrological variables by multivariate statistical
      analyses. Results show that species turnover with displacement of sensitive
      species by tolerant species was the dominating process in benthic diatom
      communities during high flow disturbances. Functional features, as indicated by
      functional diversity and redundancy indices, were mediated mainly by high and low
      flow magnitude. Median daily flow magnitude shows a consistent positive
      relationship with functional redundancy and richness indices indicating that
      larger streams are more resilient to flow perturbations. In addition flow regime
      changes are less important than median daily flow magnitude and show inconsistent
      correlation to functional features likely due to the interaction of multiple
      environmental stressors. Our study highlights the robustness of trait-based
      approaches for identifying flow regime changes in streams, and strongly suggests
      that biodiversity conservation and water resource management should focus on
      protecting natural base flow in headwater streams and generally reduce flow
      regulation for sustaining stream ecosystems under future global changes.

PMID- 30240920
TI  - Long-term and inter-monthly dynamics of aquatic vegetation and its relation with
      environmental factors in Taihu Lake, China.
AB  - This paper discussed the long-term and inter-monthly variation in the
      distribution area of aquatic macrophytes in Taihu Lake, as well as the
      relationship between these variations and environmental factors. The findings
      were of great significance to the protection and environmental remediation of
      lake ecosystems. This paper presented data from 92 periods during 1980 to 2017 on
      the distribution area of aquatic macrophytes (including submerged macrophytes and
      floating-leaved macrophytes, but excluding emergent macrophytes) in Taihu Lake.
      Data were acquired by remote-sensing and subsequent image interpretation. The
      analysis of the inter-monthly variation indicated that the area occupied by
      aquatic macrophytes first increased and then decreased from January to December.
      Specifically, the distribution area was very small from January to March, began
      to increase gradually from April to August, reached its maximum in September, and
      decreased gradually from October to December. The analysis of the long-term
      variation showed that the distribution and area of aquatic macrophytes
      experienced two stages during the years 1980 to 2017: 1) gradual increase, 2)
      sharp decrease. In the first stage (1980 to 2014), the area occupied by aquatic
      macrophytes increased by 9 times, the maximum distribution area was 206.27 km2
      (in May), 307.92 km2 (in September) and 277.33 km2 (in October). In the second
      stage (2015 to 2017), the distribution area of aquatic macrophytes decreased
      sharply to 50 km2 or less. The distribution area of aquatic macrophytes during
      the months of January to December had a significant positive correlation with
      monthly average temperature, CODMn value, secchi disk depth(SDD), area of
      cyanobacteria and chlorophyll-a (Chl-a) concentration, a significant negative
      correlation with water quality indices such as dissolved oxygen (DO) value and
      NH3-N concentration, but no significant correlation with water quality indices
      such as pH values and total suspended matter (TSM) concentration. The
      distribution area of aquatic macrophytes from 1980 to 2017 had a significant
      positive correlation with annual average temperature, annual minimum water level,
      pH value, SDD, area of cyanobacteria and Chl-a concentration, but no significant
      correlation with water quality indices such as DO value, CODMn value, NH3-N
      concentration and TSM concentration. The sharp decrease in the distribution area
      of aquatic macrophytes in 2015 and subsequent years was primarily due to the
      mechanized salvage of aquatic plants.

PMID- 30240921
TI  - A comprehensive analysis of interseasonal and interannual energy and water
      balance dynamics in semiarid shrubland and forest ecosystems.
AB  - Accurate estimation of ecosystem-scale land surface energy and water balance has
      great importance in weather and climate studies. This paper summarizes seasonal
      and interannual fluctuations of energy and water balance components in two
      distinctive semiarid ecosystems, sagebrush (SB) and lodgepole pine (LP) in the
      Snake River basin of Idaho. This study includes 6 years (2011-2016) of eddy
      covariance (EC) along with modeled estimates. An analysis of the energy balance
      indicated a higher energy balance ratio (0.88) for SB than for LP (0.86). The
      inclusion of canopy storage (CS) increased the association between turbulent
      fluxes and available energy in LP. Green vegetation fraction (GVF) significantly
      controlled evapotranspiration (ET) and surface energy partitioning when available
      energy and soil moisture were not limited. Seasonal water balance in the Budyko
      framework showed severe water-limited conditions in SB (6-9 months) compared to
      LP (6-7 months). Based on the validated Noah land surface model estimates, direct
      soil evaporation (ESoil) is the main component of ET (62 to 79%) in SB due to a
      large proportion of bare soil (60%), whereas at the lodgepole pine site, it was
      transpiration (ETran, 42-52%). A complementary ratio (CR) analysis on ET and
      potential ET (PET) showed a strong asymmetric CR in SB, indicating significant
      advection. Both SG and LP showed strong coupling between soil moisture (SM) and
      air temperature (Ta). However, a weak coupling was observed in SB when the soil
      was dry and Ta was high. This weak coupling was due to the presence of net
      advection. The results presented here have a wider application: to help us
      understand and predict the survival, productivity, and hydroclimatology of water
      limited ecosystems.

PMID- 30240922
TI  - Effects of simvastatin on the PXR signaling pathway and the liver histology in
      Mugilogobius abei.
AB  - Simvastatin is one of the most commonly cholesterol-lowering prescribed drugs all
      over the world. With the increase of consumption of these pharmaceuticals and
      subsequent their discharge into the aquatic environment in recent years, they are
      present at detectable levels in most sewage effluents. Unfortunately, limited
      information is provided about their potential impacts on aquatic organisms,
      especially on the detoxification-related metabolism in fish. In the present
      study, one local native benthic fish (Mugilogobius abei) in southern China was
      employed as test species and exposed to SV (0.5 MUg L-1, 5 MUg L-1, 50 MUg L-1
      and 500 MUg L-1) for 72 h. The transcriptional expression of nucleus
      transcriptional factor pregnane X receptor (PXR) and its downstream targeted
      genes including multixenobiotics resistance protein or permeability glycoprotein
      (P-gp), cytochrome 1A (CYP1A), cytochrome P450 3A (CYP3A), glutathione-S
      transferase (GST) and the expression of associated microRNA such as miR-27, miR
      34 and miR-148 in Mugilogobius abei were investigated. Result showed that the
      expressions of P-gp, CYP 1A, CYP 3A, GST and PXR were induced to some extend
      under simvastatin exposure for 72 h. A positive correlation was observed between
      PXR and CYP1A, CYP3A and P-gp. While for microRNA, a negative relationship was
      found between miR-34a and CYP3A, CYP1A. The expression of miR-148a was
      significantly induced under the exposure of SV (50 MUg L-1), which was positive
      related to the transcriptional expression of PXR. For enzyme activity,
      erythromycin N-demethylase (ERND) significantly increased at 24 h and the
      activity of catalase (CAT) and superoxide dismutase (SOD) exhibited different
      trends. CAT was slightly inhibited at 24 h exposure but SOD was significantly
      induced in high concentration. Glutathione-S-transferase (GST) activity was
      significant inhibited after 72 h exposure. The reductive small molecule
      glutathione (GSH) content showed obvious decrease, while the quantity of
      malondialdehyde (MDA) increased significantly in high concentrations of SV
      exposure. GSH and MDA showed a typical negative correlation to some degree.
      Moreover, simvastatin caused histological changes in the liver tissues of M.
      abei, especially the size of adipocyte significantly decreased. The present study
      indicated that environmentally relevant concentration SV may affect the PXR
      signaling pathway in M. abei and pose potential ecological risks to non-target
      organisms like fish.

PMID- 30240923
TI  - Zooplankton grazing pressure is insufficient for primary producer control under
      elevated warming and nutrient levels.
AB  - Within a given ecosystem, species persistence is driven by responses to the
      effects of biotic and abiotic stressors. Ongoing climatic shifts and increased
      pollution pressure have created the need to assess potential effects and
      interactions of physical and biotic factors on coastal ecosystem processes to
      project ecosystem resilience and persistence. In coastal marine environments,
      primary production dynamics are driven by the interaction between bottom-up
      abiotic effects and biotic effects induced by top-down trophic control. Given the
      many environmental and climatic changes observed throughout coastal regions, we
      assessed the effects of interactions among temperature, nutrients and grazing in
      a laboratory-based microcosm experiment. We did this by comparing chlorophyll-a
      (chl-a) concentrations at two temperatures in combination with four nutrient
      regimes. To test for subsequent cascading effects on higher trophic levels, we
      also measured grazing and growth rates of the calanoid copepod Pseudodiaptomus
      hessei. We observed different phytoplankton and zooplankton responses to
      temperature (17  degrees C, 24  degrees C) and nutrients (nitrogen only (N),
      phosphates only (P), nitrogen and phosphates combined (NP), no nutrient additions
      (C)). Contributions of predictors to model fit in the boosted regression trees
      model were phosphates (42.7%), copepods (23.8%), nitrates (17.5%) and temperature
      (15.9%), suggesting phosphates were an important driver for the high chl-a
      concentrations observed. There was an increase in total phytoplankton biomass
      across both temperatures, while nutrient addition affected the phytoplankton size
      structure prior to grazing irrespective of temperature. Phytoplankton biomass was
      highest in the NP treatment followed by the N treatment. However, the
      phytoplankton size structure differed between temperatures, with
      microphytoplankton being dominant at 24  degrees C, while nanophytoplankton
      dominated at 17  degrees C. The P and C treatments exhibited the lowest
      phytoplankton biomass. Copepod abundances and growth rates were higher at 17 
      degrees C than at 24  degrees C. This study highlights that bottom-up positive
      effects in one trophic level do not always positively cascade into another
      trophic level. It was, however, evident that temperature was a limiting factor
      for plankton abundance, productivity and size structure only when nutrients were
      limiting, with top-down pressure exhibiting minimal effects on the phytoplankton.

PMID- 30240924
TI  - From ash pond to Riverside Wetlands: Making the business case for engineered
      natural technologies.
AB  - The 2015 announcement of The Dow Chemical Company's (Dow) Valuing Nature Goal,
      which aims to identify $1 billion in business value from projects that are better
      for nature, gives nature a spot at the project design table. To support this
      goal, Dow and The Nature Conservancy have extended their long-standing
      collaboration and are now working to develop a defensible methodology to support
      the implementation of the goal. This paper reviews the nature valuation
      methodology framework developed by the Collaboration in support of the goal. The
      nature valuation methodology is a three-step process that engages Dow project
      managers at multiple stages in the project design and capital allocation
      processes. The three-step process identifies projects that may have a large
      impact on nature and then promotes the use of ecosystem service tools, such as
      the Ecosystem Services Identification and Inventory Tool, to enhance the project
      design so that it better supports ecosystem health. After reviewing the nature
      valuation methodology, we describe the results from a case study of redevelopment
      plans for a 23-acre site adjacent to Dow's Michigan Operations plant along the
      Tittabawassee River.

PMID- 30240925
TI  - A high glucose level is associated with decreased aspirin-mediated acetylation of
      platelet cyclooxygenase (COX)-1 at serine 529: A pilot study.
AB  - : Diabetes is a major risk factor for cardiovascular diseases. Although aspirin
      is considered a cornerstone of the prevention and treatment of atherothrombotic
      related ischemic events, this antiplatelet drug appears to be less effective in
      patients with poorly controlled diabetes. It has been suggested that the
      glycation of platelet proteins plays a pivotal role in poor responsiveness to
      aspirin. However, a direct effect on the critical residue (serine 529, or Ser
      529) of the catalytic pocket of cyclooxygenase 1 (COX-1) has never been
      demonstrated. This pilot study aimed to elucidate the impact of hyperglycaemia on
      aspirin acetylation of COX-1 using a targeted mass spectrometry approach. We
      observed that high glucose concentration had a direct impact on the level of
      acetylation of the COX-1 Ser 529 residue, whereas it's overall acetylation level
      remained unchanged. Moreover, the functional aspirin-induced inhibition of COX-1
      was dose-dependently impaired as glucose concentrations increased. These in vitro
      findings were in line with data obtained using platelets from diabetic patients.
      These data provide new insights into the interplay between glucose and aspirin on
      platelet proteins and their effects on platelet COX-1. They also suggest a
      potential mechanistic explanation for the phenomenon of poor response to aspirin
      in diabetic patients. Data are available via ProteomeXchange with identifier
      PXD011204. SIGNIFICANCE: Deciphering the mutual interplay between glucose and
      aspirin-mediated acetylation on platelet COX-1, might be of great interest as
      there is still a lack of information of the mechanism underlying this process
      that may contribute to the less-than expected response of platelets to aspirin,
      often observed in diabetes.

PMID- 30240927
TI  - Curcumin-mediated antimicrobial photodynamic therapy reduces the viability and
      vitality of infected dentin caries microcosms.
AB  - BACKGROUND: To our knowledge, there is a lack of evidence on the effect of
      Antimicrobial Photodynamic Therapy (aPDT) by the application of curcumin against
      complex biofilms of dental caries lesions. This study aimed to evaluate the
      viability, vitality, and acid metabolism of infected dentin caries microcosms
      treated with curcumin-mediated aPDT. METHODS: After microcosm biofilms growing
      anaerobically on bovine dentin disks immersed in McBain medium with 1% sucrose at
      37  degrees C for 5 days, the biofilms were treated by the association of DMSO
      water solution or 600 MUmol L-1 curcumin with 0, 37.5 or 75 J cm-2 blue LED (455
      nm). Then, the colony-forming units (CFU) counts of total microorganisms, total
      streptococci, mutans streptococci, and total lactobacilli were determined by
      plating. The lactic acid concentration was analyzed by enzymatic
      spectrophotometry method, while the vitality of intact biofilms was evaluated by
      confocal laser scanning microscope (CLSM). Statistical analysis was performed by
      Kruskal Wallis and post-hoc Dunn's tests (P < 0.05). RESULTS: Curcumin alone did
      not affect the viability of microorganisms and the vitality of intact biofilms.
      However, 75 J cm-2 LED alone decreased the total microorganisms and total
      lactobacilli counts. The combination of curcumin and LED reduced significantly
      the counts of all microorganism groups and the vitality of intact biofilms.
      Differences were not observed between the lactic acid concentrations of distinct
      groups. CONCLUSIONS: Therefore, curcumin-mediated aPDT was effective in reducing
      the viability and the vitality of infected dentin caries microcosms, without
      interfering in their acidogenicity.

PMID- 30240926
TI  - Combined CB2 receptor agonist and photodynamic therapy synergistically inhibit
      tumor growth in triple negative breast cancer.
AB  - Triple negative breast cancer (TNBC) is the deadliest form of breast cancer
      because it is more aggressive, diagnosed at later stage and more likely to
      develop local and systemic recurrence. Many patients do not experience adequate
      tumor control after current clinical treatments involving surgical removal,
      chemotherapy and/or radiotherapy, leading to disease progression and
      significantly decreased quality of life. Here we report a new combinatory therapy
      strategy involving cannabinoid-based medicine and photodynamic therapy (PDT) for
      the treatment of TNBC. This combinatory therapy targets two proteins upregulated
      in TNBC: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and
      translocator protein (TSPO, a mitochondria membrane receptor). We found that the
      combined CB2R agonist and TSPO-PDT treatment resulted in synergistic inhibition
      in TNBC cell and tumor growth. This combinatory therapy approach provides new
      opportunities to treat TNBC with high efficacy. In addition, this study provides
      new evidence on the therapeutic potential of CB2R agonists for cancer.

PMID- 30240928
TI  - Photodynamic therapy for Bowen's Disease (squamous cell carcinoma in situ)
      current review and update.
AB  - The aim of this review is to provide clinicians with an overview of outcomes in
      the current literature concerning the use of Photodynamic Therapy to treat
      Bowen's Disease, also known as Squamous Cell Carcinoma in situ. The review
      discusses clinical response, recurrence rates, cosmetic outcomes, and adverse
      effects. Strong evidence shows that PDT is an effective therapy for SCCis with
      acceptable clinical response rates and lower recurrence rates in comparison to
      conventional therapies such as cryotherapy and 5-fluorouracil. Furthermore, PDT
      is associated with superior cosmetic outcomes and is generally well tolerated by
      patients, with minimal side effects. PDT is especially useful in patients with
      multiple lesions and those whom are considered to be non-surgical candidates.

PMID- 30240930
TI  - Decolorization and detoxification of water-insoluble Sudan dye by Shewanella
      putrefaciens CN32 co-cultured with Bacillus circulans BWL1061.
AB  - Effluents loaded with various synthetic dyes are considered as a huge burden to
      the surrounding ecosystems. Sudan dyes are relatively difficult to decolorize due
      to its water-insolubility. In the present study, the strain Shewanella
      putrefaciens CN32 was firstly applied to decolorize Sudan dyes under the
      anaerobic condition, and the physicochemical parameters on the decolorization
      were optimized. The results demonstrated that the suitable decolorization
      condition was temperature 26  degrees C, initial pH 7.0-8.0 and NaCl
      concentrations 0-20 g/L. Electron competitive acceptors including nitrite,
      nitrate, dimethyl sulphoxide and oxygen could cause the significant inhibition to
      the decolorization of Sudan dyes. Biosurfactant rhamnolipid played a positive
      role in enhancing the decolorization of Sudan I. The co-culture of S.
      putrefaciens CN32 and Bacillus circulans BWL1061 is reported for the first time
      to accelerate the decolorization through improving the synergistic effect of
      enzymatic degradation and biological reductive effect. The highest decolorization
      of 90.23% to Sudan I was achieved within 108 h, suggesting that co-culture
      technique has a good potential in the treatment of dyeing wastewater.
      Furthermore, the microbial toxicity tests indicated that the toxicity of Sudan I
      to Escherichia coli BL21 and Bacillus subtilis 168 was obviously decreased after
      the decolorization.

PMID- 30240929
TI  - Novel high-gluten flour physically cross-linked graphene oxide composites:
      Hydrothermal fabrication and adsorption properties for rare earth ions.
AB  - Graphene oxide (GO) nanosheets were immobilized and cross-linked by high-gluten
      flour (HGF), and a series of biomass-GO composites with various HGF-to-GO mass
      ratios were fabricated through a one-step hydrothermal method. The HGF-GO
      composites were used as novel adsorbents to adsorb rare earth ions (REE3+: La3+,
      Yb3+, Y3+, Er3+ and Nd3+) from aqueous solutions, and their adsorption properties
      were also investigated detailly. To evaluate the physicochemical properties of
      HGF-GO composites and further understand the mechanisms of adsorption of REE3+
      onto HGF-GO composites, the HGF-GO composites were characterized by scanning
      electron microscopy (SEM), thermal gravimetric analyzer (TGA), Raman spectroscopy
      and Fourier transform infrared (FT-IR) spectroscopy. Several important condition
      parameters including contact time, initial REE3+concentrations, solution pH
      values and temperature that might affect the adsorption process were studied in
      detail. The maximum adsorption capacities of HGF-GO1:1 composite toward La3+,
      Yb3+, Y3+, Er3+ and Nd3+ were 30.32, 36.64, 32.84, 42.36 and 48.68 mg g-1,
      respectively. The experimental data indicated that the adsorption of REE3+ onto
      HGF-GO1:1 was well fitted by the pseudo-second order kinetic model and the
      Langmuir isotherm model, and the adsorption process was a spontaneous and
      endothermic reaction. The HGF-GO1:1 composite could be well regenerated and
      reused after five adsorption-desorption cycles, and its removal efficiency for
      Yb3+ remained as a constant of 100%.

PMID- 30240931
TI  - Foliar sprays of salicylic acid and jasmonic acid stimulate H+-ATPase activity of
      tonoplast, nutrient uptake and salt tolerance of soybean.
AB  - This research was conducted as factorial on the basis of randomized complete
      block design with three replications to evaluate the effects of salicylic acid (1
      mM SA), jasmonic acid (0.5 mM JA) and SA+JA on H+-ATPase hydrolytic activity of
      tonoplast in soybean roots under 0, 4, 7 and 10 dS m-1 NaCl levels. The H+-ATPase
      hydrolytic activity of tonoplast was increased under 4 dS m-1, but with rising
      salinity up to 7 and 10 dS m-1, the activity of H+-ATPase and ATP content were
      decreased in root cells. Root growth, potassium, calcium, magnesium and iron
      contents in plant tissues were decreased, while sodium, manganese, zinc and
      copper contents were increased by salinity, leading to a reduction in chlorophyll
      content index (CCI), relative water content (RWC), plant biomass and grain yield
      of soybean. Treatment of plants with SA, JA and SA+JA improved H+-ATPase activity
      and ATP content in root cells. JA treatment also reduced root growth, thereby
      limited sodium uptake by roots and translocation to the shoots. Foliar spray of
      JA only increased magnesium and iron contents in plant tissues, with no
      significant effect on other cations. In contrast, SA and SA+JA improved root
      growth and enhanced most of the cations, CCI, RWC, plant biomass and consequently
      grain yield under different levels of salinity. The SA+JA was a superior
      treatment in diminishing the harmful effects of salinity on soybean plant
      performance, compared with individual application of these growth regulators.

PMID- 30240932
TI  - After polio: Imagining, planning, and delivering a world beyond eradication.
AB  - As the world comes closer to the eradication of polio, the question of preparing
      for life after this debilitating disease becomes increasingly pertinent. This
      paper focuses on on-going institutional attempts to conceptualise, plan, and
      deliver a world after polio. Drawing upon interviews with global health officials
      and ethnographic fieldwork with eradication initiatives in Nigeria and Pakistan,
      I explore how international donors are transitioning towards life after the
      disease and the curtailment of the substantial resources it has successfully
      mobilised. Focusing specifically on the wind-down of the Global Polio Eradication
      Initiative, I critically examine key risks emerging from polio transition and
      highlight a series of spatial and political assumptions about the emergent post
      polio contours of global health that have largely been obscured by attempts to
      render transition planning as little more than a technical exercise.

PMID- 30240933
TI  - Physical activity as a mediator of the associations between perceived
      environments and body mass index in Chinese adolescents.
AB  - This study examined whether physical activity (PA) mediated the relationships of
      four PA-related environmental settings (home, school, neighborhood environments
      and convenient facilities) with body mass index (BMI) among Chinese adolescents
      aged 13-18 years. Two setting indicators were assessed: (1) perceived
      availability of environmental resources and (2) perceived importance of
      environmental resources. Mediation analysis indicated that PA mediated the
      associations of perceived availability of the home environment, convenient
      facilities, and perceived importance of the school environment and BMI z-score
      with ratios of mediating to total effects of 46.2%, 37.1%, and 37.5%
      respectively. Findings suggest that PA is a mechanism by which several
      environmental correlates may affect adolescents' body weight.

PMID- 30240934
TI  - Green infrastructure and violence: Do new street trees mitigate violent crime?
AB  - Exposure to violence has been deemed as a public health epidemic due to its
      negative impact on mental health outcomes, especially for residents of
      neighborhoods where violent crime is prevalent. Access to nature has the
      potential to mitigate diminished mental health outcomes, such as aggression.
      However, current literature specifying effective and equitable green
      infrastructure practices is lacking. The purpose of this study was to measure the
      extent to which Portland's green infrastructure initiative reduced neighborhood
      violence by increasing the availability of new trees to residents of underserved
      communities as a modality for green infrastructure intervention. Lagged
      multilevel modeling was used to determine whether an increase in new street trees
      resulted in reduced violent crime counts in the years following the planting of
      the trees. Results indicated that there was a strong negative correlation between
      the number of trees planted and violent crimes in the years following the
      planting of trees, net of neighborhood covariates. This effect was especially
      pronounced in neighborhoods with lower median household income. These findings
      suggest that the inclusion of new street trees in underserved neighborhoods may
      be one solution to the endemic of violence in such neighborhoods.

PMID- 30240936
TI  - Dose-response relationship between ambulatory load magnitude and load-induced
      changes in COMP in young healthy adults.
AB  - OBJECTIVE: To determine the dose-response relationship between ambulatory load
      magnitude during a walking stress test and load-induced changes in serum
      concentration of cartilage oligomeric matrix protein (sCOMP) in healthy subjects.
      DESIGN: sCOMP was assessed before and after a 30-min walking stress test
      performed on three test days by 24 healthy volunteers. In each walking stress
      test, one of three ambulatory loads was applied in a block randomized crossover
      design: normal body weight (BW) (100%BW = normal load); reduced BW (80%BW =
      reduced load); increased BW (120%BW = increased load). Knee kinematics and ground
      reaction force (GRF) were measured using an inertial sensor gait analysis system
      and a pressure plate embedded in the treadmill. RESULTS: Load-induced increases
      in sCOMP rose with increasing ambulatory load magnitude. Mean sCOMP levels
      increased immediately after the walking stress test by 26.8 +/- 12.8%, 28.0 +/-
      13.3% and 37.3 +/- 18.3% for the reduced, normal or increased load condition,
      respectively. Lower extremity kinematics did not differ between conditions.
      CONCLUSIONS: The results of this study provide important evidence of a dose
      response relationship between ambulatory load magnitude and load-induced changes
      in sCOMP. Our data suggests that in normal weight persons sCOMP levels are more
      sensitive to increased than to reduced load. The experimental framework presented
      here may form the basis for studying the relevance of the dose-response
      relationship between ambulatory load magnitude and load-induced changes in
      biomarkers involved in metabolism of healthy articular cartilage and after
      injury.

PMID- 30240935
TI  - More than gangsters and girl scouts: Environmental health perspectives of urban
      youth.
AB  - The purpose of this study was to explore environmental health perspectives among
      urban youth. A total of 12 focus groups with 64 youth were conducted. Youth
      defined environmental health in a multidimensional manner which integrated
      aspects of the physical, social, and built environment and concentrated on the
      neighborhood context. A theme of environmental health resilience factors and sub
      themes of safety, trust, engagement, leadership, and representation were
      identified and described. A second theme of underlying structural drivers of
      environmental health with sub-themes of equitable opportunities and power inform
      environmental health. A conceptual model was developed to guide future
      environmental health research and action.

PMID- 30240937
TI  - CGRP blockade by galcanezumab was not associated with reductions in signs and
      symptoms of knee osteoarthritis in a randomized clinical trial.
AB  - OBJECTIVE: This study tested whether galcanezumab, a humanized monoclonal
      antibody with efficacy against migraine, was superior to placebo for the
      treatment of mild or moderate osteoarthritis (OA) knee pain. METHOD: In a
      multicenter, double-blind, placebo- and celecoxib-controlled trial, patients with
      moderate to severe OA pain were randomized to placebo; celecoxib 200 mg daily for
      16 weeks; or galcanezumab 5, 50, 120, and 300 mg subcutaneously every 4 weeks,
      twice. The primary outcome was change from baseline at Week 8 in Western Ontario
      and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore measured by
      100 mm visual analog scale (VAS). The trial was considered positive if >=1 dose
      of galcanezumab demonstrated >=95% Bayesian posterior probability of superiority
      to placebo and >=50% posterior probability of superiority to placebo by >=9 mm. A
      planned interim analysis allowed termination of the study if posterior
      probability of superiority to placebo by >=9 mm was <=5%. Secondary endpoints
      included WOMAC function subscore and Patient Global Assessment (PGA) of OA.
      Safety and tolerability were also assessed. RESULTS: The study was terminated
      after interim analysis suggested inadequate efficacy. Celecoxib significantly
      reduced WOMAC pain subscore compared with placebo [-12.0 mm; 95% confidence
      interval (CI) -23 to -2 mm]. None of the galcanezumab arms demonstrated
      clinically meaningful improvement (range: 1.5 to -5.0 mm) or met the prespecified
      success criteria. No improvement in any secondary objective was observed.
      Galcanezumab was well tolerated by OA patients. CONCLUSIONS: This study failed to
      demonstrate sufficient statistical evidence that galcanezumab was efficacious for
      treating OA knee pain. STUDY IDENTIFICATION: NCT02192190.

PMID- 30240938
TI  - The effects of metabolic syndrome, obesity, and the gut microbiome on load
      induced osteoarthritis.
AB  - OBJECTIVE: Metabolic syndrome is characterized by obesity, hyperglycemia,
      hypertension, insulin resistance, and dyslipidemia. Metabolic syndrome is
      associated with osteoarthritis (OA), but it is unclear if the association is
      attributable to increased mechanical loading on joints caused by obesity or other
      aspects of metabolic syndrome. Here we examined the effects of altered
      metabolism, obesity, and the gut microbiome on load-induced OA. DESIGN: Cartilage
      damage was induced through cyclic compressive loading in four groups of adult
      male mice: Toll-like receptor-5 deficient (TLR5KO) mice that develop metabolic
      syndrome due to alterations in the gut microbiome, TLR5KO mice submitted to
      chronic antibiotics to prevent metabolic syndrome (TLR5KODeltaMicrobiota),
      C57BL/6J mice fed a high fat diet to cause obesity (HFD), and untreated C57BL/6J
      mice (WT). Loading was applied for 2 weeks (n = 10-11/group) or 6 weeks (n = 10
      11/group). RESULTS: After 2 weeks of loading, cartilage damage (OARSI score) was
      not different among groups. After 6 weeks of loading, HFD mice had increased load
      induced cartilage damage, while TLR5KO mice had cartilage damage comparable to WT
      mice. TLR5KODeltaMicrobiota mice had less cartilage damage than other groups. HFD
      mice had elevated serum inflammatory markers. Each group had a distinct gut
      microbiome composition. CONCLUSIONS: Severe obesity increased load-induced
      cartilage damage, while milder changes in adiposity/metabolic syndrome seen in
      TLR5KO mice did not. Furthermore, the effects of systemic inflammation/obesity on
      cartilage damage depend on the duration of mechanical loading. Lastly, reduced
      cartilage damage in the TLR5KODeltaMicrobiota mice suggests that the gut
      microbiome may influence cartilage pathology.

PMID- 30240939
TI  - Associations between serum S100A8/S100A9 and knee symptoms, joint structures and
      cartilage enzymes in patients with knee osteoarthritis.
AB  - OBJECTIVE: Animal studies suggest that S100A8/S100A9 may be involved in the
      pathogenesis of osteoarthritis (OA); however, there has been no clinical study
      examining the associations between serum S100A8/S100A9 and knee symptoms, joint
      structures and cartilage degradation enzymes in knee OA patients so far.
      Therefore, this study was designed to investigate the cross-sectional
      associations between serum levels of S100A8/S100A9 and the outcomes in patients
      with knee OA. DESIGN: A total of 141 subjects with clinical knee OA were
      included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
      score was used to assess joint symptoms. Magnetic resonance imaging (MRI) was
      used to measure knee structural abnormalities including cartilage defects. Knee
      radiography was used to assess joint space narrowing (JSN), osteophytes and the
      radiographic severity of OA. Enzyme-linked immunosorbent assay (ELISA) was used
      to measure the serum levels of S100A8/S100A9, matrix metalloproteinase (MMP)-3,
      MMP10 and MMP13. RESULTS: In multivariable analyses, serum S100A8/S100A9 were
      positively associated with total WOMAC score (beta: 0.111 per 10 ng/ml, P =
      0.021), WOMAC weight-bearing pain (beta: 0.015 per 10 ng/ml, P = 0.043) and WOMAC
      physical dysfunction (beta: 0.091 per 10 ng/ml, P = 0.010), and had positive
      associations with total cartilage defects and cartilage defects at lateral
      femoral, lateral tibial and medial femoral sites (ORs: 1.006-1.008 per 10 ng/ml,
      all P < 0.05) and serum levels of MMP3 (beta: 0.002 per 10 ng/ml, P = 0.032) in
      patients with clinical knee OA. CONCLUSIONS: Serum levels of S100A8/S100A9 were
      positively associated with increased knee symptoms, cartilage defects and serum
      cartilage degradation enzymes in patients with knee OA, suggesting that
      S100A8/S100A9 may have a role to play in knee OA. Future longitudinal studies are
      required to confirm these findings.

PMID- 30240940
TI  - Cryo-EM of ATP synthases.
AB  - ATP synthases are rotary enzymes found in bacteria, chloroplasts, and
      mitochondria. These complexes produce the majority of cellular ATP in aerobic
      cells using energy from the transmembrane proton motive force established by the
      electron transport chain. In mitochondria, dimeric ATP synthase is essential for
      formation of the inner membrane cristae. While rotary catalysis in the soluble F1
      region has been studied extensively by X-ray crystallography, the structure of
      the membrane embedded FO region remained elusive until recently. In the past few
      years, electron cryomicroscopy structures of mitochondrial, chloroplast, and
      bacterial ATP synthases have revealed the architecture of the FO region, helping
      to explain the mechanisms of proton translocation, dimerization of the enzyme in
      mitochondria, and cristae formation. These structures also show that ATP
      synthases exist in different conformational states, illustrating the flexibility
      and dynamics of the complex.

PMID- 30240941
TI  - Measurement of plasma HIV-1 RNA below the limit of quantification (<20 copies/mL)
      of commercial assays with the integrase HIV RNA single-copy assay.
AB  - BACKGROUND: Plasma HIV-1 RNA (viral load, VL) is measured routinely in HIV
      infected persons with FDA-approved commercially available assays such as the
      Cobas-TaqMan HIV-1 Assay v2.0. This assay provides quantification of viremia >=20
      copies/mL. More sensitive methods, able to quantify low-level persistent viremia
      below the detection limit of commercially available assays, are needed to assess
      the impact of current HIV cure strategies on viremia. OBJECTIVES: The novel
      integrase HIV-1 RNA single-copy assay (iSCA) was evaluated for measurement of low
      level persistent viremia in clinical trial samples (n = 151) from subjects
      participating in Gilead HIV clinical research. STUDY DESIGN: Paired plasma
      samples from HIV-1-infected patients treated with combination ART were assessed
      using both HIV-1 Cobas-TaqMan and iSCA; results from the two assays were
      compared. RESULTS: Paired Cobas-TaqMan/iSCA data were obtained for 151 HIV
      infected adults. Most samples (117/151, 77%) had non-quantifiable Cobas-TaqMan
      result, either <20 copies/mL ("<20") or "Target Not Detected" (TND). All 117 non
      quantified samples were quantified with iSCA and showed higher HIV-1 RNA levels
      in samples with <20 than TND Cobas-TaqMan results (p < 0.0001). CONCLUSIONS: In
      this large sample collection from virologically suppressed HIV-infected adults,
      use of iSCA led to quantification of low-level viremia below the limit of
      detection of the Cobas-TaqMan assay in all 117 previously non-quantifiable plasma
      samples. These data confirm the value of the iSCA as a helpful addition to the
      classical HIV VL assays and its potential for use in HIV cure studies to assess
      whether experimental interventions alter viremia.

PMID- 30240942
TI  - Neurocognitive outcomes after aneurysmal subarachnoid hemorrhage: Identifying
      inflammatory biomarkers.
AB  - Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke which
      carries a high case-fatality rate. Those who survive the ictus of aneurysm
      rupture harbor substantial risks of neurological morbidity, functional
      disability, and cognitive dysfunction. Although the pervasiveness of cognitive
      impairment is widely acknowledged as a long-term sequela of aSAH, the mechanisms
      underlying its development are poorly understood. The onset of aSAH elicits
      activation of the inflammatory cascade, and ongoing neuroinflammation is
      suspected to contribute to secondary complications, such as vasospasm and delayed
      cerebral ischemia. In this review, we analyze the extant literature regarding the
      relationship between neuroinflammation and cognitive dysfunction after aSAH. Pro
      inflammatory cytokines appear to play a role in maintaining normal cognitive
      function in adults unaffected by aSAH. However, in the setting of aSAH, elevated
      cytokine levels may correlate with worse neuropsychological outcomes. This
      seemingly dichotomous relationship between neuroinflammation and cognition
      suggests that the action of cytokines varies, depending on their physiologic
      environment. Experimental therapies which suppress the immune response to aSAH
      appear to have a beneficial effect on cognitive outcomes. However, further
      studies are necessary to determine the utility of inflammatory mediators as
      biomarkers of neurocognitive outcomes, as well as their role in the management of
      aSAH.

PMID- 30240943
TI  - Collateral circulation assessment within the 4.5 h time window in patients with
      and without DWI/FLAIR MRI mismatch.
AB  - OBJECTIVES: The aim of the present study was to assess the association between
      collateral status and DWI-FLAIR mismatch in patients with acute ischemic stroke
      within the 4.5 h time-window. METHODS: We analysed DWI, FLAIR, and PWI data in
      patients within 4.5 h after symptom onset from the I-KNOW European database.
      Collateral flow maps were graded by analyzing contrast 'staining' extent over the
      early, mid and late perfusion phases. ADC values, DWI lesion volume, and
      normalised perfusion parameters (CBV,Tmax) within DWI lesions were determined.
      Visibility of parenchymal hyperintensivty on FLAIR was evaluated ("FLAIR
      positive"), and DWI-FLAIR mismatch was assessed. Spontaneously reperfused regions
      were defined as voxels with Tmax <6 s within the DWI lesion. Final infarct size
      was assessed on day-30 FLAIR images. RESULTS: Of the 168 patients included in I
      KNOW database, 87 were eligible for this study. DWI-FLAIR mismatch was present in
      69 patients. There was no difference between poor and good collaterals status
      according to age, sex, baseline NIHSS score, time to MRI and DWI lesion volume.
      Collateral status was significantly better in the FLAIR positive group (p =
      .001). Patients with poor collaterals had significantly increased Tmax (p =
      .005). Baseline DWI lesion volume and final lesion volume were significantly
      smaller in patients with good collateral status (p < .001 and 0.01,
      respectively). CONCLUSIONS: We found that patients with early FLAIR lesion
      visibility have a better collateral status. This finding has implications for the
      management of stroke patients with unknown time-of-onset, and more widely should
      be considered in the current context of extending the therapeutic window.

PMID- 30240944
TI  - Multifaceted effects of arachidonic acid and interaction with cyclic nucleotides
      in human platelets.
AB  - INTRODUCTION: Arachidonic acid induced aggregation is a generally accepted test
      for aspirin resistance. However, doubts have been raised that arachidonic acid
      stimulated aggregation can be regarded as reliable testing for aspirin
      resistance. Arachidonic acid, in addition to platelet activation, can induce
      phosphatidylserine translocation on the outer surface of platelet membrane which
      could be mediated by apoptosis pathways or transformation of platelets to the
      procoagulant state. MATERIALS AND METHODS: We explored effects of arachidonic
      acid over a vast range of concentrations and a wide range of read-outs for human
      platelet activation, procoagulant activity, and platelet viability. Additionally
      we tested whether cAMP- or cGMP-dependent protein kinase activation can inhibit
      procoagulant activity or platelet viability. RESULTS: Arachidonic acid-induced
      washed platelet activation was detected at low micromolar concentrations during
      the first 2 min of stimulation. After longer incubation and/or at higher
      concentrations arachidonic acid triggered platelet procoagulant activity and
      reduced platelet viability. At the same time, arachidonic acid stimulated
      adenylate cyclase mediated protein phosphorylation which correlated with reduced
      platelet activation. Moreover, additional stimulation of cAMP- or cGMP-dependent
      protein kinase inhibited only platelet activation, but did not prevent pro
      coagulant activity and platelet death. CONCLUSIONS: While arachidonic acid
      induces platelet activation at low concentrations and during short incubation
      time, higher concentrations and lasting incubation evokes adenylate cyclase
      activation and subsequent protein phosphorylation corresponding to reduced
      platelet activation, but also enhanced pro-coagulant activity and reduced
      viability. Our observations provide further proof for the complex fine tuning of
      platelet responses in a time and agonist concentration dependent manner.

PMID- 30240945
TI  - Decline of auditory-motor speech processing in older adults with hearing loss.
AB  - Older adults often experience difficulties in understanding speech, partly
      because of age-related hearing loss (HL). In young adults, activity of the left
      articulatory motor cortex is enhanced and it interacts with the auditory cortex
      via the left-hemispheric dorsal stream during speech processing. Little is known
      about the effect of aging and age-related HL on this auditory-motor interaction
      and speech processing in the articulatory motor cortex. It has been proposed that
      upregulation of the motor system during speech processing could compensate for HL
      and auditory processing deficits in older adults. Alternatively, age-related
      auditory deficits could reduce and distort the input from the auditory cortex to
      the articulatory motor cortex, suppressing recruitment of the motor system during
      listening to speech. The aim of the present study was to investigate the effects
      of aging and age-related HL on the excitability of the tongue motor cortex during
      listening to spoken sentences using transcranial magnetic stimulation and
      electromyography. Our results show that the excitability of the tongue motor
      cortex was facilitated during listening to speech in young and older adults with
      normal hearing. This facilitation was significantly reduced in older adults with
      HL. These findings suggest a decline of auditory-motor processing of speech in
      adults with age-related HL.

PMID- 30240946
TI  - Beta-sheet assembly of Tau and neurodegeneration in Drosophila melanogaster.
AB  - The assembly of Tau into abundant beta-sheet-rich filaments characterizes human
      tauopathies. A pathological pathway leading from monomeric to filamentous Tau is
      believed to be at the heart of these diseases. However, in Drosophila models of
      Tauopathy, neurodegeneration has been observed in the absence of abundant Tau
      filaments. Here we investigated the role of Tau assembly into beta-sheets by
      expressing wild-type and Delta306-311 human Tau-383 in the retina and brain of
      Drosophila. We analyzed both lines for eye abnormalities, brain vacuolization,
      Tau phosphorylation and assembly, as well as climbing activity and survival.
      Flies expressing wild-type Tau-383 showed MC-1 staining, Tau
      hyperphosphorylation, and neurodegeneration. By contrast, flies expressing
      Delta306-311 Tau-383 had less MC-1 staining, reduced Tau hyperphosphorylation,
      and no detectable neurodegeneration. Their climbing ability and lifespan were
      similar to those of nontransgenic flies. Fluorescence spectroscopy after addition
      of Thioflavin T, a dye that interacts with beta-sheets, showed no signal when
      Delta306-311 Tau-383 was incubated with heparin. These findings demonstrate that
      the assembly of Tau into beta-sheets is necessary for neurodegeneration.

PMID- 30240947
TI  - Anatomic distribution of endometriosis: A reappraisal based on series of 1101
      patients.
AB  - OBJECTIVE: To reappraise the anatomic distribution of endometriosis lesions in
      cases with Superficial Implants (SI), Ovarian Endometrioma (OMA) and Deep
      Infiltrating Endometriosis (DIE). MATERIALS AND METHODS: A prospective
      observational study was operated between January 1989 to June 2009. A total of
      1333 consecutive patients with a laparoscopic diagnosis of endometriosis, were
      extracted from our database. Due to missing data or repeated operations, 232
      patients were excluded from the study. Finally, 1101 patients who met the
      selected criteria were included in the present analysis.. Primary outcome of
      study was the anatomic location of endometriotic lesions. Secondary outcomes were
      laterality of lesions as well as location of adhesions. RESULTS: Mean age of
      patients was 33.06 years (range 15-63 years) while the mean BMI was 21.5. The
      ovary was the most frequent site of endometriotic lesions (737 patients, 66.94%)
      followed by the utero-sacral ligaments (USL) (45.51%), the ovarian fossa
      (32.15%), the pouch of Douglas (29.52%) and the bladder (21.25%). Deep
      Infiltrating Endometriosis (DIE) was diagnosed in 159 patients (14.4%) with an
      increasing rate starting from the mid-nineties. The left side was predominant for
      all locations except fromr ovarian SI and fallopian tube, but for this latter
      location the number of cases was limited. 600 (54.4%) patients had adhesions wjth
      the adnexa being the most frequent site of location (47.4%). CONCLUSIONS: Ovary
      was the main site of endometriotic lesions followed by the utero sacral
      ligaments. Left side was predominant for all locations except for ovarian SI and
      fallopian tube. The diagnosis of DIE has constantly being increased since mid
      nineties. The large cohort of patients included in the study has strengthened
      previous reported data.

PMID- 30240948
TI  - Expanded carrier screening: A current perspective.
AB  - Prenatal carrier screening has expanded to include a large number of genes
      offered to all couples considering pregnancy or with an ongoing pregnancy.
      Expanded carrier screening refers to identification of carriers of single-gene
      disorders outside of traditional screening guidelines. Expanded carrier screening
      panels include numerous autosomal recessive and X-linked genetic conditions,
      including those with a very low carrier frequency, as well as those with mild or
      incompletely penetrant phenotype. Therefore, the clinical utility of these panels
      is still subject of debate. Priority should be given to carrier screening panels
      that include a comprehensive set of severe childhood-onset disorders.
      Psychosocial support and genetic couseling should be available prior to screening
      and for the return of positive results. Systems are needed to reduce the risk of
      misinterpreting results. Finally, attention should be paid on the impact of
      expanded carrier screening on health care organizations and burden of cost.

PMID- 30240950
TI  - The critical needs and challenges for genetic architecture studies in Africa.
AB  - Human genetic studies have long been vastly Eurocentric, raising a key question
      about the generalizability of these study findings to other populations. Because
      humans originated in Africa, these populations retain more genetic diversity, and
      yet individuals of African descent have been tremendously underrepresented in
      genetic studies. The diversity in Africa affords ample opportunities to improve
      fine-mapping resolution for associated loci, discover novel genetic associations
      with phenotypes, build more generalizable genetic risk prediction models, and
      better understand the genetic architecture of complex traits and diseases subject
      to varying environmental pressures. Thus, it is both ethically and scientifically
      imperative that geneticists globally surmount challenges that have limited
      progress in African genetic studies to date. Additionally, African investigators
      need to be meaningfully included, as greater inclusivity and enhanced research
      capacity afford enormous opportunities to accelerate genomic discoveries that
      translate more effectively to all populations. We review the advantages,
      challenges, and examples of genetic architecture studies of complex traits and
      diseases in Africa. For example, with greater genetic diversity comes greater
      ancestral heterogeneity; this higher level of understudied diversity can yield
      novel genetic findings, but some methods that assume homogeneous population
      structure and work well in European populations may work less well in the
      presence of greater heterogeneity in African populations. Consequently, we
      advocate for methodological development that will accelerate studies important
      for all populations, especially those currently underrepresented in genetics.

PMID- 30240949
TI  - Application of a sperm survival test: Results from an external quality control
      programme.
AB  - OBJECTIVE: The study aim is to determine which type of material - pipette tips or
      culture medium - is more appropriate for use in a cytotoxicity external quality
      control programme (CT-EQC). STUDY DESIGN: The results of the participating
      laboratories in Spanish CT-EQC programme for human reproduction laboratories
      during the period 2013-2016 were analyzed. Per year, laboratories receiving three
      pipette tips and three aliquots of culture medium. All laboratories used the
      human sperm survival test to perform the bioassay. On average 48 laboratories
      took part in the programme each year. Sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV) and overall accuracy were
      calculated, with the corresponding 95% confidence intervals. RESULTS: Overall,
      for both products, sensitivity was higher than specificity, and NPV was higher
      than PPV. For laboratories participating for the first time in the CT-EQC, lower
      results were obtained in sensitivity and specificity in culture media than in
      pipette tips. However, in subsequent years, these differences disappeared. The
      PPV obtained for pipette tips was higher than that obtained for culture media
      (0.82 (0.77-0.87) vs 0.71 (0.66-0.76)). No relationship was recorded between the
      laboratories' accuracy in culture media and pipette tips (r = 0.026).
      CONCLUSIONS: From a logistical standpoint, pipette tips are more appropriate than
      culture medium for use in a CT-EQC programme.

PMID- 30240951
TI  - Lipopeptisomes: Anticancer peptide-assembled particles for fusolytic oncotherapy.
AB  - Anticancer peptides (ACPs) are cationic amphiphiles that preferentially kill
      cancer cells through folding-dependent membrane disruption. Although ACPs
      represent attractive therapeutic candidates, particularly against drug-resistant
      cancers, their successful translation into clinical practice has gone unrealized
      due to their poor bioavailability, serum instability and, most importantly,
      severe hemolytic toxicity. Here, we exploit the membrane-specific interactions of
      ACPs to prepare a new class of peptide-lipid particle, we term a lipopeptisome
      (LP). This design sequesters loaded ACPs within a lipid lamellar corona to avoid
      contact with red blood cells and healthy tissues, while affording potent lytic
      destruction of cancer cells following LP-membrane fusion. Biophysical studies
      show ACPs rapidly fold at, and integrate into, liposomal membranes to form stable
      LPs with high loading efficiencies (>80%). Rational design of the particles to
      possess lipid combinations mimicking that of the aberrant cancer cell outer
      leaflet allows LPs to rapidly fuse with tumor cell membranes and afford localized
      assembly of loaded ACPs within the bilayer. This leads to preferential fusolytic
      killing of cancer cells with minimal collateral toxicity towards non-cancerous
      cells and erythrocytes, thereby imparting clinically relevant therapeutic indices
      to otherwise toxic ACPs. Thus, integration of ACPs into self-assembled LPs
      represents a new delivery strategy to improve the therapeutic utility of
      oncolytic agents, and suggests this technology may be added to targeted
      combinatorial approaches in precision medicine. STATEMENT OF SIGNIFICANCE:
      Despite their significant clinical potential, the therapeutic utility of many
      ACPs has been limited by their collateral hemolysis during administration.
      Leveraging the membrane-specific interactions of ACPs, here we prepare self
      assembled peptide-lipid nanoparticles, or 'lipopeptisomes' (LPs), capable of
      preferentially fusing with and lysing cancer cell membranes. Key to this
      fusolytic action is the construction of LPs from lipids simulating the cancer
      cell outer leaflet. This design recruits the oncolytic peptide payload into the
      carrier lamella and allows for selective destruction of cancer cells without
      disrupting healthy cells. Consequently, LPs impart clinically relevant
      therapeutic indexes to previously toxic ACPs, and thus open new opportunities to
      improve the clinical translation of oncolytics challenged by narrow therapeutic
      windows.

PMID- 30240952
TI  - A systematic electron microscopic study on the uptake of barium sulphate nano-,
      submicro-, microparticles by bone marrow-derived phagocytosing cells.
AB  - Nanoparticles can act as transporters for synthetic molecules and biomolecules
      into cells, also in immunology. Antigen-presenting cells like dendritic cells are
      important targets for immunotherapy in nanomedicine. Therefore, we have used
      primary murine bone marrow-derived phagocytosing cells (bmPCs), i.e. dendritic
      cells and macrophages, to study their interaction with spherical barium sulphate
      particles of different size (40 nm, 420 nm, and 1 um) and to follow their uptake
      pathway. Barium sulphate is chemically and biologically inert (no dissolution, no
      catalytic effects), i.e. we can separate the particle uptake effect from
      potential biological reactions. The colloidal stabilization of the nanoparticles
      was achieved by a layer of carboxymethylcellulose (CMC) which is biologically
      inert and gives the particles a negative zeta potential (i.e. charge). The
      particles were made fluorescent by conjugating 6-aminofluoresceine to CMC. Their
      uptake was visualized by flow cytometry, confocal laser scanning microscopy
      (CLSM), scanning electron microscopy (SEM), transmission electron microscopy
      (TEM), and correlative light and electron microscopy (CLEM). Barium sulphate
      particles of all sizes were readily taken up by dendritic cells and even more by
      macrophages, with the uptake increasing with time and particle concentration.
      They were mainly localized inside phagosomes, heterophagosomes, and in the case
      of nanoparticles also in the nearby cytosol. No particles were found in the
      nucleus. In nanomedicine, inorganic nanoparticles from the nanometer to the
      micrometer size are therefore well suited as transporters of biomolecules,
      including antigens, into dendritic cells and macrophages. The presented model
      system may also serve to describe the aseptic loosening of endoprostheses caused
      by abrasive wear of inert particles and the subsequent cell reaction, a question
      which relates to the field of nanotoxicology. STATEMENT OF SIGNIFICANCE: The
      interaction of particles and cells is at the heart of nanomedicine and
      nanotoxicology, including abrasive wear from endoprostheses. It also comprises
      the immunological reaction to different kinds of nanomaterials, triggered by an
      immune response, e.g. by antigen-presenting cells. However, it is often difficult
      to separate the particle effect from a chemical or biochemical reaction to
      particles or their cargo. We show how chemically inert barium sulphate particles
      with three different sizes (nano, sub-micro, and micro) interact with relevant
      immune cells (primary dendritic cells and macrophages). Particles of all three
      sizes are readily taken up into both cell types by phagocytosis, but the uptake
      by macrophages is significantly more prominent than that by dendritic cells. The
      cells take up particles until they are virtually stuffed, but without direct
      adverse effect. The uptake increases with time and particle concentration. Thus,
      we have an ideal model system to follow particles into and inside cells without
      the side effect of a chemical particle effect, e.g. by degradation or ion
      release.

PMID- 30240953
TI  - Targeted cellular delivery of robust enzyme nanoparticles for the treatment of
      drug-induced hepatotoxicity and liver injury.
AB  - Direct delivery of proteins into cells has been considered an effective approach
      for treating the protein-related diseases. However, clinical use of proteins has
      still been limited due to their instability in the blood and poor membrane
      permeability. To achieve an efficient cellular delivery of the protein to target
      cells via a systemic administration, a multifunctional carrier system having
      desirable stability both in the blood stream and the cells, specific cell
      targeting property and endosomal escape functions may be required. In this study,
      we prepared a catalytic nanoparticle containing an active enzyme by cross
      tethering multiple superoxide dismutase (SOD) molecules with catechol-derivatized
      hyaluronic acid (HA). The permeable shell of hydrophilic HA chains effectively
      protects the enzyme from degradation in the blood after intravenous
      administration and provides an additional function for targeting hepatocytes
      expressing HA receptor (CD44). The structure and catalytic activity of the enzyme
      molecules in the nanoparticle were not significantly compromised in the
      nanoparticle. In addition, ultra-small calcium phosphate nanoparticles (USCaP, 2
      5 nm) were crystalized and decorated on the surface of the nanoparticle for the
      efficient endosomal escape after cellular uptake. The SOD-containing nanoparticle
      fortified with USCaP was used for the treatment of acetaminophen (APAP)-induced
      fulminant hepatotoxicity and liver injury. The nanoparticle achieved the
      efficient hepatic cellular delivery of SOD via a systemic administration and
      resulted in efficient removal of reactive oxygen species (ROS) in the liver and
      remarkable improvement of APAP-induced hepatotoxicity and liver injury in
      animals. STATEMENT OF SIGNIFICANCE: Despite the enormous therapeutic potential,
      the intracellular delivery of proteins has been limited due to their poor
      membrane permeability and stability. In this study, we demonstrated an active
      enzyme-containing nanoparticle functionalized by hyaluronic acid and ultra-small
      size calcium phosphate nanoparticles (2-5 nm) for targeted cellular delivery of
      superoxide dismutase (SOD). The nanoparticle was designed to integrate all the
      essential functions, including serum stability, target specificity, and endosomal
      escape capability, for a systemic delivery of a therapeutic protein to the cells
      of the liver tissue. The intravenous administration of the nanoparticle
      efficiently removes reactive oxygen species (ROS) in the liver and remarkably
      improves the drug-induced hepatotoxicity and the progress of fulminant liver
      injury in an acetaminophen-overdose animal model.

PMID- 30240954
TI  - Energy dissipation in mammalian collagen fibrils: Cyclic strain-induced damping,
      toughening, and strengthening.
AB  - As the fundamental structural protein in mammals, collagen transmits cyclic
      forces that are necessary for the mechanical function of tissues, such as bone
      and tendon. Although the tissue-level mechanical behavior of collagenous tissues
      is well understood, the response of collagen at the nanometer length scales to
      cyclical loading remains elusive. To address this major gap, we cyclically
      stretched individual reconstituted collagen fibrils, with average diameter of 145
      +/- 42 nm, to small and large strains in the partially hydrated conditions of 60%
      relative humidity. It is shown that cyclical loading results in large steady
      state hysteresis that is reached immediately after the first loading cycle,
      followed thereafter by limited accumulation of inelastic strain and constant
      initial elastic modulus. Cyclic loading above 20% strain resulted in 70% increase
      in tensile strength, from 638 +/- 98 MPa to 1091 +/- 110 MPa, and 70% increase in
      toughness, while maintaining the ultimate tensile strain of collagen fibrils not
      subjected to cyclic loading. Throughout cyclic stretching, the fibrils maintained
      a steady-state hysteresis, yielding loss coefficients that are 5-10 times larger
      than those of known homogeneous materials in their modulus range, thus
      establishing damping of nanoscale collagen fibrils as a major component of
      damping in tissues. STATEMENT OF SIGNIFICANCE: It is shown that steady-state
      energy dissipation occurs in individual collagen fibrils that are the building
      blocks of hard and soft tissues. To date, it has been assumed that energy
      dissipation in tissues takes place mainly at the higher length scales of the
      tissue hierarchy due to interactions between collagen fibrils and fibers, and in
      limited extent inside collagen fibrils. It is shown that individual collagen
      fibrils need only a single loading cycle to assume a highly dissipative, steady
      state, cyclic mechanical response. Mechanical cycling at large strains leads to
      70% increase in mechanical strength and values exceeding those of engineering
      steels. The same cyclic loading conditions also lead to 70% increase in toughness
      and loss properties that are 5-10 times higher than those of engineering
      materials with comparable stiffness.

PMID- 30240955
TI  - A light-controllable specific drug delivery nanoplatform for targeted bimodal
      imaging-guided photothermal/chemo synergistic cancer therapy.
AB  - Breast cancer is a severe threat to the health and lives of women due to its
      difficult early diagnosis and the unsatisfactory therapeutic efficacy of breast
      cancer treatments. The development of theranostic strategies to combat breast
      cancer with high accuracy and effectiveness is therefore urgently needed. In this
      study, we describe a near-infrared (NIR) light-controllable, targeted and
      biocompatible drug delivery nanoplatform (PFH-PTX@PLGA/SPIO-Her) for
      photoacoustic (PA)/ultrasound (US) bimodal imaging-guided photothermal
      (PTT)/chemo synergistic cancer therapy of breast cancer. Carboxyl-modified
      PEGylated poly (lactic-co-glycolic acid) (PLGA-PEG-COOH) constituted the skeleton
      of the nanoplatform. Especially, the antibody Herceptin was modified onto the
      surface of nanoplatform for active HER2-targing to facilitate the tumor
      accumulation of the nanoplatform. The encapsulated superparamagnetic iron oxide
      (SPIO) nanoparticles could be employed as an excellent PA imaging agent to guide
      tumor therapy. When exposed to NIR light, the SPIO also could transform NIR light
      into thermal energy for photothermal ablation of tumor. The NIR-induced thermal
      effect subsequently triggered the optical droplet vaporization (ODV) of
      perfluorohexane (PFH) to generate PFH gas bubbles, which not only achieved the US
      imaging enhancement, but also contributed to the release of loaded paclitaxel
      (PTX) from the nanoplatform for significantly improving PTT therapeutic efficacy.
      Our results demonstrated that the targeted tumor accumulation, accurate real-time
      bimodal imaging, and the abundant drug release at the tumor site were all closely
      associated with the PTT therapeutic efficacy. Therefore, the theranostic
      nanoplatform is a very promising strategy for targeted imaging-guided
      photothermal/chemo synergistic tumor therapy with high therapeutic efficacy and
      minimized side effects. STATEMENT OF SIGNIFICANCE: Breast cancer is the most
      frequent cancer in women. Herein, we successfully developed a light-controllable
      and HER2 targeted theranostic nanoparticels (PFH-PTX@PLGA/SPIO-Her) as a specific
      drug delivery nanoplatform to overcome the low accuracy of tumor detection and
      the low specificity of traditional chemo-therapeutic protocols. The study
      demonstrated that PFH-PTX@PLGA/SPIO-Her could actively target to breast cancer
      cells with positive HER2 expression. The biocompatible PFH-PTX@PLGA/SPIO-Her
      nanoparticles as both photoacoustic/ultrasound bimodal imaging agents,
      photothermal-conversion nanomaterials (photothermal hyperthermia) and
      controllable drug delivery nanoagents (optical droplet vaporization) have
      completely eradicated the tumor without severe side effects. The theranostic
      strategy not only integrates strengthens of traditional imaging or therapeutic
      modalities, but also paves a new way for the efficient cancer treatment by taking
      the advantage of quickly-developing nanomedicine.

PMID- 30240956
TI  - Hyaluronic acid shell and disulfide-crosslinked core micelles for in vivo
      targeted delivery of bortezomib for the treatment of multiple myeloma.
AB  - Bortezomib (BTZ) provides one of the best treatments for multiple myeloma (MM).
      The efficacy of BTZ is, nevertheless, restricted by its fast clearance, low
      selectivity, and dose limiting toxicities. Here, we report on targeted BTZ
      therapy of MM in vivo by hyaluronic acid-shelled and core-disulfide-crosslinked
      biodegradable micelles (HA-CCMs) encapsulating lipophilized BTZ, bortezomib
      pinanediol (BP). HA-CCMs loaded with 7.3 BTZ equiv. wt% exhibited a small size of
      78 nm, good stability in 10% FBS, and glutathione-triggered drug release. MTT
      assays in CD44 positive LP-1 multiple myeloma cells revealed that BP encapsulated
      in HA-CCMs caused enhanced antiproliferative effect compared with free BP. Flow
      cytometry, confocal microscopy and MTT assays indicated BP-loaded HA-CCMs (HA
      CCMs-BP) could actively target to LP-1 cells and induce high antitumor effect.
      Proteasome activity assays in vitro showed HA-CCMs-BP had a similar proteasome
      activity inhibition as compared to free BTZ at 18 h. The fluorescence imaging
      using Cy5-labeled HA-CCMs showed that HA-CCMs had a long elimination half-life
      and enhanced tumor accumulation via HA-mediated uptake mechanism. The therapeutic
      studies in LP-1 MM-bearing mice revealed better treatment efficacy of HA-CCMs-BP
      compared with free BTZ, in which HA-CCMs-BP at 3 mg BTZ equiv./kg brought about
      significant tumor growth inhibition and survival benefits. Loading of
      lipophilized BTZ into HA-shelled multifunctional micelles has emerged as an
      exciting approach for bortezomib therapy of MM. STATEMENT OF SIGNIFICANCE:
      Multiple myeloma (MM) is the second most common hematological malignancy.
      Bortezomib (BTZ), a potent proteasome inhibitor, provides one of the best
      treatments for MM. The clinical efficacy of BTZ is, however, limited by its quick
      clearance, poor selectivity, and significant side effects including
      myelosuppression and peripheral neuropathy. Here, we report on targeted BTZ
      therapy of MM in vivo by hyaluronic acid-shelled and core-disulfide-crosslinked
      biodegradable micelles (HA-CCMs) encapsulating lipophilized BTZ, bortezomib
      pinanediol (BP). Our results showed that BP-loaded HA-CCMs exhibit markedly
      enhanced toleration, broadened therapeutic window, and significantly more
      effective growth suppression of CD44-overexpressed multiple myeloma in nude mice
      than free bortezomib. Lipophilized BTZ-loaded HA-CCMs has opened a new avenue for
      targeted bortezomib therapy of multiple myeloma.

PMID- 30240957
TI  - CDC25B promotes influenza A virus replication by regulating the phosphorylation
      of nucleoprotein.
AB  - Cell division cycle 25 B (CDC25B) is a member of the CDC25 phosphatase family. It
      can dephosphorylate cyclin-dependent kinases and regulate the cell division
      cycle. Moreover, siRNA knockdown of CDC25B impairs influenza A virus (IAV)
      replication. Here, to further understand the regulatory mechanism of CDC25B for
      IAV replication, a CDC25B-knockout (KO) 293T cell line was constructed using
      CRISPR/Cas9. The present data indicated that the replication of IAV was decreased
      in CDC25B-KO cells. Additionally, CDC25B deficiency damaged viral polymerase
      activity, nucleoprotein (NP) self-oligomerization, and NP nuclear export. Most
      importantly, we found that the NP phosphorylation levels were significantly
      increased in CDC25B-KO cells. These findings indicate that CDC25B facilitates the
      dephosphorylation of NP, which is vital for regulating NP functions and the life
      cycle of IAV.

PMID- 30240959
TI  - Understanding age-induced cortical porosity in women: Is a negative BMU balance
      in quiescent osteons a major contributor?
AB  - Cortical bone is remodeled by intracortical basic multicellular units (BMUs),
      whose end result can be observed as quiescent osteons in histological sections.
      These osteons offer a unique opportunity to investigate the BMU balance between
      the magnitude of bone resorption and subsequent bone formation at the BMU level.
      Our main objective was to investigate whether the latter parameters change
      between defined categories of osteons and with age, and to which extend these
      changes contribute to age-induced cortical porosity. Cortices of iliac bone
      specimens from 35 women (aged 16-78 years) with a higher porosity with age were
      investigated. A total of 3084 quiescent osteons reflecting 75% of the
      intracortical pores were histological examined. The osteons diameter, pore
      diameter, wall thickness, prevalence and contribution to the porosity were highly
      variable, but unchanged with age. Next, the osteons were categorized according to
      whether they reflected the remodeling of existing canals (type 2Q osteons) or the
      generation of new canals (type 1Q osteons). Type 2Q osteons versus type 1Q
      osteons: (i) had more frequently a pore diameter > 75 MUm (7.4 vs. 1.3%; p <
      0.001); (ii) had a larger mean pore diameter (40 +/- 10 vs. 25 +/- 4 MUm; p <
      0.001), osteon diameter (120 +/- 21 vs. 94 +/- 21 MUm; p < 0.001) and wall
      thickness (40 +/- 10 vs. 35 +/- 9; p < 0.05); (iii) had a larger contribution to
      the cortical porosity (29 +/- 18 vs. 8 +/- 8%; p < 0.001); (iv) were more
      prevalent (44 +/- 10 vs. 31 +/- 11%; p < 0.001); and (v) were more prevalent with
      age. Collectively, this study demonstrates that quiescent osteons with age more
      frequently result from remodeling of existing canals, which in some cases had a
      more negative BMU balance. Still, the osteons showed no overall age-related
      change in their pore diameter i.e. BMU balance. In contrast to conventional
      wisdom, these data show that non-quiescent pores, not pores of quiescent osteons,
      were the main contributor to a higher cortical porosity.

PMID- 30240958
TI  - Endoplasmic reticulum-mediated induction of interleukin-8 occurs by hepatitis B
      virus infection and contributes to suppression of interferon responsiveness in
      human hepatocytes.
AB  - The events in the immune response to hepatitis B virus (HBV) remain unclear. We
      analyzed the direct influence of HBV on gene expression in human hepatocytes
      under immunodeficient conditions using a human hepatocyte chimeric mouse model.
      HBV-infected or non-infected chimeric mouse livers were collected, and gene
      expression profiles were compared. Since IL-8 was the most significantly up
      regulated gene at 8 weeks after HBV infection, we focused on IL-8 and found that
      HBx and the large HBs (L-HBs) protein induce transcription of IL-8 via
      endoplasmic reticulum stress. This stress induces IL-8 transcription via NFAT
      activation and contributes to suppression of interferon responsiveness in HBV
      infected human hepatocytes. In the present study, we identified a novel
      regulatory mechanism in which the L-HBs protein activates IL-8 via endoplasmic
      reticulum stress, suggesting a key role for IL-8 in the immune response to HBV
      and a potential new target for antiviral treatments of HBV infection.

PMID- 30240960
TI  - Age at menarche and osteoporosis: A Mendelian randomization study.
AB  - PURPOSE: Traditional epidemiological studies suggest that there is an association
      between age at menarche (years) (AAM) and bone mineral density (BMD) at the sites
      of the femoral neck and lumbar spine (FNK and LS BMD), indicating a potentially
      important relationship between AAM and the development of osteoporosis (OP).
      However, these findings may be influenced by unmeasured confounding factors that
      can obscure the true relationship between the phenotypic traits. Therefore, we
      performed Mendelian randomization (MR) analyses to determine whether there is a
      causal relationship between AAM and BMD (FNK and LS BMD), where late AAM may
      increase the risk of developing OP. METHODS: Adopting a two-sample MR approach we
      incorporated genome-wide association (GWAS) summary statistics from the
      Reproductive Genetics (ReproGen) Consortium (n = 182,416) (females only) and the
      GEnetic Factors for OSteoporosis (GEFOS) Consortium (n = 53,236) (both males and
      females). RESULTS: Using this MR approach we discovered that each additional year
      in AAM is associated with a modest reduction in FNK BMD (beta = -0.072 se =
      0.022, 95% CI (-0.115, -0.030), p = 0.001) and LS BMD ((beta = -0.072, se =
      0.025, 95% CI (-0.121, -0.023), p = 0.004), and therefore influences OP
      susceptibility. CONCLUSIONS: This study demonstrates that AAM in females may play
      a causal role in OP etiology and provides novel insights into the pathophysiology
      of bone related diseases like osteoporosis, osteopenia and fracture. SUMMARY: Our
      study demonstrates that AAM in females may play a causal role in OP etiology and
      provides novel insights into the pathophysiology of bone related diseases like
      osteoporosis, osteopenia and fracture. By adopting Mendelian Randomization
      approaches, our study was not susceptible to bias from unmeasured confounders or
      reverse causation.

PMID- 30240961
TI  - Biofidelic finite element models for accurately classifying hip fracture in a
      retrospective clinical study of elderly women from the AGES Reykjavik cohort.
AB  - Clinical retrospective studies have only reported limited improvements in hip
      fracture classification accuracy using finite element (FE) models compared to
      conventional areal bone mineral density (aBMD) measurements. A possible
      explanation is that state-of-the-art quasi-static models do not estimate patient
      specific loads. A novel FE modeling technique was developed to improve the
      biofidelity of simulated impact loading from sideways falling. This included
      surrogate models of the pelvis, lower extremities, and soft tissue that were
      morphed based on subject anthropometrics. Hip fracture prediction models based on
      aBMD and FE measurements were compared in a retrospective study of 254 elderly
      female subjects from the AGES-Reykjavik study. Subject fragility ratio (FR) was
      defined as the ratio between the ultimate forces of paired biofidelic models, one
      with linear elastic and the other with non-linear stress-strain relationships in
      the proximal femur. The expected end-point value (EEV) was defined as the FR
      weighted by the probability of one sideways fall over five years, based on self
      reported fall frequency at baseline. The change in maximum volumetric strain
      (DeltaMVS) on the surface of the femoral neck was calculated between time of
      ultimate femur force and 90% post-ultimate force in order to assess the extent of
      tensile tissue damage present in non-linear models. After age-adjusted logistic
      regression, the area under the receiver-operator curve (AUC) was highest for
      DeltaMVS (0.72), followed by FR (0.71), aBMD (0.70), and EEV (0.67), however the
      differences between FEA and aBMD based prediction models were not deemed
      statistically significant. When subjects with no history of falling were excluded
      from the analysis, thus artificially assuming that falls were known a priori with
      no uncertainty, a statistically significant difference in AUC was detected
      between DeltaMVS (0.85), and aBMD (0.74). Multivariable linear regression
      suggested that the variance in maximum elastic femur force was best explained by
      femoral head radius, pelvis width, and soft tissue thickness (R2 = 0.79; RMSE =
      0.46 kN; p < 0.005). Weighting the hip fracture prediction models based on self
      reported fall frequency did not improve the models' sensitivity, however
      excluding non-fallers lead to significant differences between aBMD and FE based
      models. These findings suggest that an accurate assessment of fall probability is
      necessary for accurately identifying individuals predisposed to hip fracture.

PMID- 30240962
TI  - Diet quality in persons with and without depressive and anxiety disorders.
AB  - OBJECTIVE: This study examines the association of depressive and anxiety
      disorders and their clinical characteristics (disorder type, severity, chronicity
      and clinical subtypes) with diet quality. METHOD: Data from 1634 adults (controls
      = 336, current disorder = 414, remitted = 886) were sourced from the 9-year
      follow-up of the Netherlands Study of Depression and Anxiety. Depressive and
      anxiety disorders were established with Composite International Diagnostic
      Interviews. Severity was measured with the Inventory of Depressive Symptomatology
      (IDS), Fear Questionnaire and the Beck Anxiety Inventory. Chronicity was measured
      with life-chart interviews expressed as percentage time with a disorder(s). Diet
      quality was evaluated using the Mediterranean Diet Score (MDS) and the
      Alternative Healthy Eating Index (AHEI). RESULTS: Diet quality was significantly
      worse among subjects with a current disorder than among healthy controls.
      Subdividing subjects showed that those with concurrent depressive and anxiety
      disorders had the lowest diet quality score (MDS: beta = -0.41 per SD, 95%
      Confidence interval (95%CI) = -0.60, -0.21; AHEI beta = -0.22 per SD 95% CI = 
      0.42,-0.03). More chronic depression or anxiety disorders and increased severity
      in all participants showed a dose-response association with poorer diet quality.
      There was no distinct pattern between IDS items related to depression subtypes
      and diet quality. CONCLUSION: Diet quality is poorer in persons with depressive
      and anxiety disorders; in particular in those with comorbidity. The more severe
      and chronic the symptoms, the poorer the diet quality. Prospective studies are
      needed to confirm the direction of the relationship of depressive and anxiety
      disorders with diet quality and to examine whether improving diet quality could
      improve mental health.

PMID- 30240963
TI  - Comorbidity of personality disorder with intermittent explosive disorder.
AB  - There is ambiguity in how recurrent anger and aggression are accounted for by
      psychiatric nosology. One area of uncertainty is the extent to which Intermittent
      Explosive Disorder (IED) overlaps with and is distinct from Personality Disorder
      (PD). Accordingly, we conducted a study of individuals with IED and PD in order
      to understand the nature of comorbidity relationships seen across these two areas
      of psychopathology. One-thousand-five-hundred-twenty-one adults were studied (441
      Healthy Controls (HC), 430 Psychiatric Controls (PC), and 650 IED subjects) and
      assessed for DSM-5 psychiatric disorders, life history of aggressive behavior,
      trait aggression, state and trait anger reactivity, and impulsivity. While nearly
      half of IED study participants had a comorbid PD diagnosis, nearly half with a
      Cluster B PD, almost as many had other personality disorders. IED predicted anger
      symptoms and history of aggressive behavior above and beyond a PD diagnosis.
      Comorbidity between IED and either Antisocial (AsPD) or Borderline (BPD) PD was
      associated with the highest levels of aggressive behavior. However, having IED
      comorbid with either AsPD and/or BPD PD was not associated with higher levels of
      impulsivity. Underlying personality traits related to anger, affect, and social
      behavior, but not identity disturbance, contribute to the shared symptom profile
      of IED and PD. IED is usually comorbid with PD, but does not have a unique
      relationship with any single PD. When comorbid with PD, a diagnosis of IED
      predicts more severe anger and aggression, but not necessarily increased
      impulsivity. These results suggest that IED and PD diagnoses retain clinical
      utility when made in cases meeting criteria for both.

PMID- 30240964
TI  - Induction of innate immune memory: the role of cellular metabolism.
AB  - The paradigm that only adaptive immunity can develop immunological memory has
      recently been challenged by studies showing that cells from the innate immune
      system can undergo functional reprogramming, facilitating a faster and enhanced
      response to secondary infections. This improved secondary response is not always
      specific, as it can also protect from infections caused by non-related pathogens.
      This has been termed innate immune memory or trained immunity. Trained immunity
      not only involves rewiring the intracellular immune signaling of innate immune
      cells, but also induces profound changes in cellular metabolic pathways such as
      glycolysis, oxidative phosphorylation, fatty acid and amino acid metabolism,
      increasing the capacity of the innate immune cells to respond to a secondary
      stimulation. The understanding of these intracellular processes opens new
      therapeutic possibilities for the modulation of the innate immune responses
      during infections and inflammatory diseases.

PMID- 30240965
TI  - A facile DNA strand displacement reaction sensing strategy of electrochemical
      biosensor based on N-carboxymethyl chitosan/molybdenum carbide nanocomposite for
      microRNA-21 detection.
AB  - Herein, we report a facile enzyme-free microRNA (miRNA) target-triggered strand
      displacement reaction (SDR) amplification strategy with ferrocene (Fc) as a
      signal molecule to fabricate a two-dimensional electroactive molybdenum carbide
      (Mo2C)-based biosensor. In the presence of miRNA-21, SDR was initiated and many
      hairpin DNA1 (HDNA1) and hairpin DNA2 (HDNA2) duplexes, which could be captured
      by probe DNA leading the Fc-modified HDNA2 close to the electrode surface, were
      produced continuously. MiRNA-21 could be detected by monitoring the redox signal
      of Fc. The prepared N-carboxymethyl chitosan/Mo2C nanocomposite featured
      excellent conductivity, great dispersion, and multiple functional groups (amine
      groups). When the nanocomposite was introduced to a miRNA biosensor electrode
      interface to ensure its strong connection to the DNA probe, the developed miRNA
      21 biosensor demonstrated a reliable linear range of 1.0 fM to 1.0 nM with a
      detection limit of 0.34 fM and showed good selectivity, reproducibility, and
      stability. The biosensor was employed to detect miRNA-21 in human serum samples,
      and it showed great potential in the early clinical diagnosis of various genetic
      diseases.

PMID- 30240966
TI  - Quantum dot-based electrochemical biosensor for stripping voltammetric detection
      of telomerase at the single-cell level.
AB  - Human telomerase is responsible for the maintenance of chromosome end structures
      and is a valuable biomarker for malignant growth. However, the accurate
      measurement of telomerase activity at the single-cell level has remained a great
      challenge. Here we develop a simple quantum dot (QD)-based electrochemical
      biosensor for stripping voltammetric detection of telomerase activity at the
      single-cell level. We designed a thiol-modified capture DNA which may be
      immobilized on the gold electrode by the gold-sulfur bond. The presence of
      telomerase enables the addition of the telomere repeats of (TTAGGG)n to the 3'
      end of the primer, accompanied by the incorporation of abundant biotins in the
      extension product with the assistance of the biotin-tagged dATP. The subsequent
      hybridization of extension product with the capture DNA and the addition of
      streptavidin-coated QDs induce the assembly of large amounts of QDs onto the
      electrode via specific biotin-streptavidin binding. After the acidic dissolution
      of QDs, the released Cd (II) can be simply quantified by anodic stripping
      voltammetry (ASV). Due to the introduction of large amounts of QDs by telomerase
      induced primer extension reaction and the synergistic signal amplification
      induced by the release of Cd (II) from the QDs, this biosensor can detect
      telomerase activity at the single-cell level without the involvement of any
      thermal cycling and extra enzymes for signal amplification. Moreover, this assay
      exhibits a large dynamic range over four orders of magnitude and it is very
      simple without the involvement of specific hairpin probe design and complicated
      labelling, holding great potential in point-of-need testing.

PMID- 30240967
TI  - Liquid gated ZnO nanorod FET sensor for ultrasensitive detection of Hepatitis B
      surface antigen with vertical electrode configuration.
AB  - Detection of the Hepatitis-B surface antigen at the attomolar level is
      demonstrated using antibody functionalized liquid gated ZnO nanorods field effect
      transistor (FET) biosensor with vertical electrode configuration. The sensor is
      operated in heterodyne mode at high frequency to overcome the problem of Debye
      screening effect in physiological analyte. Enhanced penetration of the electric
      field lines through the nanorods enables significant improvement in the limit of
      detection and sensitivity compared to that of the conventional lateral electrode
      configuration. The combined effect of the probable change in the threshold
      voltage and the carrier mobility for vertical electrode configuration lead to a
      sensitivity of around 75% at 1 fM (which is an enhancement by 200%) and a
      detection limit of 20 aM with a dynamic range from 20 aM to 1 pM. The detection
      limit which is achieved with the proposed label free sensor in physiological
      analyte using antibodies is lowered by more than three orders of magnitude
      compared to the existing reports.

PMID- 30240968
TI  - Refractory GERD, beyond proton pump inhibitors.
AB  - Pharmacologic therapy, surgery, minimally invasive therapies, and alternative
      therapies are different options available for the management of refractory GERD.
      The choice may depend on the cause of refractoriness. Increased gastric acid
      suppression therapy might be useful in the rare patients with persistent elevated
      esophageal acid exposure on proton pump inhibitors (PPI). Potassium-competitive
      acid blockers (P-CAB) might induce a more important acid inhibition than PPI.
      Baclofen might act as a reflux inhibitor and demonstrates a significant efficacy
      in rumination syndrome. The role of topical antacid-alginate in refractory GERD
      might be limited. Surgery might be a valid option in case of persistent
      pathological acid esophageal exposure despite PPI. Further evaluation of
      minimally invasive procedures is necessary. Finally diet, diaphragmatic breathing
      and transcutaneous electrical acustimulation might be of interest in patients
      with esophageal hypersensivity or functional symptoms.

PMID- 30240969
TI  - Synteny-based mapping of causal point mutations relevant to sand rice
      (Agriophyllum squarrosum) trichomeless1 mutant by RNA-sequencing.
AB  - Sand rice (Agriophyllum squarrosum), a diploid Amaranthaceae species within the
      order Caryophyllalles, has potential as a crop in response to concerns about
      ongoing climate change and future food security. Modifying the weedy traits, such
      as dense trichomes, is important for the domestication of sand rice. In this
      study, an ethyl methanesulfonate (EMS) induced Agriophyllum squarrosum
      trichomeless mutant (astcl1) was isolated and genetic analysis revealed that this
      mutant was controlled by a single recessive locus. RNA sequencing was employed to
      analyze sequence variations between the mutant and wild-type individuals based on
      allele frequencies. Synteny-based mapping against two closely related and
      sequenced species finally delimited the causal mutations into an approximately
      18.97 mega base pair (Mb) interval on the top portion of the chromosome 6 (Bv6)
      of sugar beet (Beta vulgaris) and two intervals (5.56 and 2.69 Mb) on the
      chromosomes 14 (CqA14) and 6 (CqB06) of quinoa (Chenopodium quinoa). These two
      quinoa intervals were located in the orthologous chromosomal regions against
      sugar beet Bv6. Differential expression analysis revealed that the astcl1
      mutation only affects the expression of a small subset of genes. Most
      significantly, 17 lipid transport and metabolism related genes, such as GDSL
      esterases and very-long-chain 3-oxoacyl-CoA reductase 1, and two R2R3 MYB genes,
      MYB39 and RAX3, were down-regulated in astcl1 mutants. These results imply that
      the Astcl1 protein coordinately regulates trichome initiation and cuticle
      biosynthesis in sand rice.

PMID- 30240970
TI  - Identifying Involvement of H19-miR-675-3p-IGF1R and H19-miR-200a-PDCD4 in
      Treating Pulmonary Hypertension with Melatonin.
AB  - Non-coding RNAs play an important role in the pathogenesis of pulmonary arterial
      hypertension (PAH). The aim of this study was to characterize the therapeutic
      role of melatonin as well as the underlying molecular mechanism (its effects on
      the expression of H19 and its downstream signaling pathways) in the treatment of
      PAH. Real-time PCR and western blot analysis were performed to evaluate the
      expression of H19, miR-200a, miR-675, insulin-like growth factor-1 receptor
      (IGF1R), and programmed cell death 4 (PDCD4). The value of systolic pulmonary
      artery pressure (SPAP) and the ratio of medial thickening in the monocrotaline
      (MCT) group were increased, whereas the melatonin treatment could decrease these
      values to some extent. The weights of RV (right ventricle), LV (left ventricle) +
      IVS (interventricular septal), and RV/(LV + IVS) in the MCT group were much
      higher than those in the MCT + melatonin and control groups. In addition, the
      expression of H19, miR-675, IGF1R mRNA, and IGF1R protein in the MCT group was
      the highest, whereas their expression in the control group was the lowest. The
      expression of miR-200, PDCD4 mRNA, and PDCD4 protein in the MCT group was the
      lowest, whereas their expression in the control group was the highest.
      Furthermore, H19 directly suppressed the expression of miR-200a, whereas miR-675
      3p and miR-200a directly inhibited the expression of IGF1R and PDCD4,
      respectively. Finally, melatonin treatment inhibited cell proliferation;
      upregulated the expression of H19, miR-675-3p, and PDCD4; and downregulated the
      expression of miR-200a and IGF1R. This study demonstrated the role of H19-miR-675
      3p-IGF1R- and H19-miR-200a-PDCD4-signaling pathways in the melatonin treatment of
      PAH.

PMID- 30240971
TI  - miR-17-3p Downregulates Mitochondrial Antioxidant Enzymes and Enhances the
      Radiosensitivity of Prostate Cancer Cells.
AB  - Radioresistance remains to be a major obstacle in the management of patients with
      advanced prostate cancer (PCa). We have identified a mature miR-17-3p processed
      from the 3' arm of precursor miR-17, which appeared to be able to inhibit three
      major antioxidant enzymes located in mitochondria, i.e., manganese superoxide
      dismutase (MnSOD), glutathione peroxidase 2 (Gpx2), and thioredoxin reductase 2
      (TrxR2). Here we show that upregulation of miR-17-3p remarkably sensitized PCa
      cells to ionizing radiation (IR). Reductions of the three antioxidants led to
      increasing cellular reactive oxygen species (ROS) accumulation as well as
      declining mitochondrial respiration. The miR-17-3p-mediated dysfunction of
      mitochondrial antioxidants apparently sensitizing IR therapy was manifested in
      vitro and in vivo. Substantially, the miR-17-3p effect on suppression of the
      antioxidants can be efficiently eliminated or attenuated by transfecting with
      either an miR-17-3p inhibitor or each of the related antioxidant cDNA expression
      constructs. Overall, in addition to the insights into the functional assessments
      for the duplex of miR-17-5p and miR-17-3p, the present study highlights the
      rigorous evidence that demonstrated suppression of multiple mitochondrial
      antioxidants by a single microRNA (miRNA), thereby providing a promising approach
      to improve radiotherapy for advanced PCa by targeting mitochondrial function.

PMID- 30240972
TI  - Combined Metabolo-Volumetric Parameters of 18F-FDG-PET and MRI Can Predict Tumor
      Cellularity, Ki67 Level and Expression of HIF 1alpha in Head and Neck Squamous
      Cell Carcinoma: A Pilot Study.
AB  - BACKGROUND: Our purpose was to evaluate associations of combined 18F-FDG-PET and
      MRI parameters with histopathological features in head and neck squamous cell
      carcinoma (HNSCC). METHODS: Overall, 22 patients with HNSCC were acquired (10
      with G1/2 tumors and 12 with G3 tumors).18F-FDG-PET/CT and MRI was performed and
      maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and
      metabolic tumor volume (MTV) were estimated. Neck MRI was obtained on a 3 T
      scanner. Diffusion weighted imaging was performed with estimation of apparent
      diffusion coefficient (ADC). Perfusion parameters Ktrans,Ve, and Kep were derived
      from dynamic contrast-enhanced (DCE) imaging. Different combined PET/MRI
      parameters were calculated as ratios: PET parameters divided by ADC or DCE MRI
      parameters. The following histopathological features were estimated: Ki 67, EGFR,
      VEGF, p53, hypoxia-inducible factor (HIF)-1alpha, and cell count. Spearman's
      correlation coefficient (p) was used for correlation analysis. P < .05 was taken
      to indicate statistical significance. RESULTS: In overall sample, cellularity
      correlated with SUVmax/ADCmin (P = .558, P = .007), TLG/ADCmin (P = .546, P =
      .009), and MTV/ADCmin (P = .468, P = .028). MTV/Kep correlated with expression of
      HIF-1alpha (P = .450, P = 0,047). In G1/2 tumors, SUVmax/ADCmin correlated with
      HIF-1alpha (P = -.648, P = .043); MTV/Kep (P = -.669, P = .034) and TLG/Kep (P = 
      .644, P = .044) with Ki67. In G3 tumors, cellularity correlated with
      SUVmax/ADCmin (P = .832, P = .001), SUVmax/ADCmean (P = .741, P = .006), and
      TLG/ADCmin (P = .678, P = .015). MTV/ADCmin and TLG/ADCmin tended to correlate
      with HIF-1alpha. CONCLUSION: Combined parameters of 18F-FDG-PET and MRI can
      reflect Ki 67, tumor cellularity and expression of HIF-1alpha in HNSCC.
      Associations between parameters of 18F-FDG-PET and MRI and histopathology depend
      on tumor grading.

PMID- 30240973
TI  - Photodynamic inactivation of Enterococcus faecalis by non-peripherally
      substituted magnesium phthalocyanines entrapped in lipid vesicles.
AB  - Photophysical properties and photodynamic antibacterial potential of magnesium
      phthalocyanines bearing 2-propoxy, benzyloxy, 3,5-bis(benzyloxy)benzyloxy
      substituents at non-peripheral positions were studied. The UV-Vis absorption
      spectra of researched phthalocyanine derivatives were found typical. Extension of
      peripheral substituent size from 2-propoxy to benzyloxy and finally 3,5
      bis(benzyloxy)benzyloxy was accompanied by the rise of quantum yield of
      fluorescence up to 0.17 and 0.04 in DMF and DMSO, respectively. Similarly, the
      expansion of the phthalocyanine periphery from the 2-propoxy to benzyloxy and 3,5
      bis(benzyloxy)benzyloxy groups resulted in a detectable increase of the singlet
      oxygen quantum yield values to 0.04, 0.12, 0.14 respectively, which was assessed
      following direct method of singlet oxygen phosphorescence measurement at 1270 nm.
      Studied phthalocyanines undergo photobleaching process with the quantum yields at
      the level of 10-6 in DMSO and 10-5 in DMF. The size of phthalocyanine impacted
      the process of liposomal formulation. Small liposome vesicles containing non
      peripherally substituted phthalocyanines with 2-propoxy and benzyloxy
      substituents were obtained following extrusion method. The unification process of
      the liposomes loaded with 3,5-bis(benzyloxy)benzyloxy non-peripherally
      substituted phthalocyanines was not possible. In in vitro antimicrobial
      photodynamic inactivation study, log reduction values of bacterial (Enterococcus
      faecalis) growth at 3.61 and 2.99 were achieved for liposomal formulations
      containing phthalocyanines with 2-propoxy and benzyloxy substituents
      respectively, whereas phthalocyanine with 3,5-bis(benzyloxy)benzyloxy
      substituents was inactive. Phthalocyanine with 2-propoxy substituents exhibited
      relatively low toxicity in Vibrio fischeri bioluminescence test, whereas
      phthalocyanine with benzyloxy substituents revealed intense bioluminescence,
      which could be associated with hormesis phenomenon.

PMID- 30240974
TI  - Methionine oxidation by hydrogen peroxide in peptides and proteins: A theoretical
      and Raman spectroscopy study.
AB  - The oxidation of proteins results in their deterioration via the oxidation of
      reactive amino acids. Oxidation of the amino acid, methionine plays an important
      role during biological conditions of oxidative stress, and equally a role in
      protein stability. In this study the oxidation of the methionine residue using
      the tripeptide GlyMetGly with respect to hydrogen peroxide has been studied using
      both Raman spectroscopy and DFT calculations. Spectral modifications following
      the formation of methionine sulfoxide are shown with the appearance of the SO
      vibration whilst there is also the modification of the CS vibrations at
      approximately 700 cm-1. The changes in the intensity of the CS stretching band
      were used to calculate the kinetic rate constant as 7.9 +/- 0.6 * 10-3 dm3 mol-1
      s-1. The energy barrier for the reaction. is determined both experimentally and
      using DFT calculations. The reaction of the dairy protein beta-lactoglobulin with
      hydrogen peroxide is equally studied using the same technique. The solvent
      accessible surface area of the methionine residues within the protein were also
      determined and a comparison of the reaction rate constant and the energy barriers
      of reaction for the oxidation of the tripeptide and for the protein respectively
      thus, provides information about the role of the protein environment in the
      oxidation process.

PMID- 30240975
TI  - Lanostane triterpenoids from Ganoderma luteomarginatum and their cytotoxicity
      against four human cancer cell lines.
AB  - Lanostane triterpenoids are major metabolites of macrofungi from the genus
      Ganoderma and possess enormous substitution diversity and remarkable biological
      activities, especially anticancer, antioxidant, and anti-inflammatory effects.
      The present phytochemical investigation resulted in the isolation of nine
      undescribed lanostane triterpenoids and five known analogues from the fruiting
      bodies of Ganoderma luteomarginatum, which was first phytochemically studied by
      our group. Chemical structures were elucidated based on spectroscopic evidence.
      (5alpha,23E)-27-nor-lanosta-8,23-dien-3,7,25-trione and (5alpha,23E)-27-nor-3beta
      hydroxylanosta-8,23-dien-7,25-dione are undescribed triterpenoids with an unusual
      27-nor-lanostane carbon skeleton. All isolates were assayed for their cytotoxic
      activities using four human cancer cell lines (HGC-27, HeLa, A549, and SMMC-7721)
      and one human normal cell line (LO2), and the structure-cytotoxicity
      relationships were preliminarily explored. (5alpha,24E)-3beta-acetoxyl-26
      hydroxylanosta-8,24-dien-7-one exhibited the highest cytotoxicity against HeLa
      and A549 cell lines, with IC50 values of 1.29 and 1.50 MUM, respectively.

PMID- 30240977
TI  - EEG coherence in a mental arithmetic task performance in first episode
      schizophrenia and schizoaffective disorder.
AB  - OBJECTIVES: To evaluate the coherence values of the cortical bands in patients
      with first episode schizophrenia and schizoaffective disorder during the
      performance of a mental arithmetic task. METHOD: We analysed EEG coherence in the
      resting state and subsequently while counting down from 200 in steps of 7 in 32
      first episode schizophrenia patients (SZ), 32 patients with first episode
      schizoaffective disorder (SA) and 40 healthy controls (HC). RESULTS: Task
      performance in HC is characterised by decreased coherence in the alpha bands and
      increased coherence in the beta 2 and gamma bands in frontal sites. In SZ,
      coherence decreases in the alpha band, whereas in SA it substantially increases
      in the alpha, beta1, beta 2 and gamma bands. CONCLUSIONS: Despite no differences
      in performance on a behavioural level, SA patients demonstrate a paradoxical
      increase in both low and fast frequency bands during the performance of a mental
      arithmetic task, while, patients with SZ show a decreased coherence in the alpha
      band, presumably alluding to the excessive excitatory (in SA) and inhibitory (in
      SZ) mechanisms in cognitive processing. SIGNIFICANCE: The current study provides
      evidence for the distinction of neurophysiological mechanisms of cognitive
      processing between SZ and SA.

PMID- 30240978
TI  - fMRI Stroop and behavioral treatment for cocaine-dependence: Preliminary findings
      in methadone-maintained individuals.
AB  - BACKGROUND: Although behavioral treatment for cocaine use disorders is common,
      the use of cognitive neuroscience methods to investigate these treatments'
      mechanisms of action remains limited. Cognitive control (e.g., as measured by the
      Stroop task) has been proposed to be central to cocaine-use disorders, including
      treatment response. METHODS: Participants were methadone-maintained, cocaine
      dependent individuals who were participating in a randomized clinical trial (RCT)
      of 8 weeks of treatment for cocaine-use disorder and randomized to outpatient
      treatment as usual (TAU) or computer-based cognitive-behavioral therapy (CBT4CBT)
      plus TAU. Participants completed fMRI Color-Word Stroop task at beginning-of
      treatment (N = 19) and post-treatment (N = 10). Analyses assessed correlations
      between beginning-of-treatment Stroop effect with methadone dose or within
      treatment cocaine abstinence, change in Stroop-effect at post- versus beginning
      of-treatment, and correlations between 'change in Stroop effect' with methadone
      dose or within-treatment cocaine abstinence. RESULTS: Higher methadone dose was
      associated with higher beginning-of-treatment Stroop-related activity in the
      declive, culmen, and lingual gyrus. Stroop-related activity was reduced at post
      treatment relative to beginning-of-treatment in the medial frontal
      gyrus/cingulate gyrus and thalamus/midbrain/culmen. Greater reduction in Stroop
      related activity was associated with better within-treatment abstinence.
      CONCLUSIONS: Diminished Stroop-related activity following treatment may be
      consistent with improved efficiency of cognitive-control-related activity.
      Although preliminary, this study is the first to demonstrate a relationship
      between better treatment outcomes (lower cocaine use during treatment) and
      greater reduction in Stroop-related activity at post- versus beginning-of
      treatment in cocaine users. These findings extend prior work.

PMID- 30240976
TI  - Intrinsic network reactivity differentiates levels of consciousness in comatose
      patients.
AB  - OBJECTIVE: We devise a data-driven framework to assess the level of consciousness
      in etiologically heterogeneous comatose patients using intrinsic dynamical
      changes of resting-state Electroencephalogram (EEG) signals. METHODS: EEG signals
      were collected from 54 comatose patients (GCS ? 8) and 20 control patients (GCS >
      8). We analyzed the EEG signals using a new technique, termed Intrinsic Network
      Reactivity Index (INRI), that aims to assess the overall lability of brain
      dynamics without the use of extrinsic stimulation. The proposed technique uses
      three sigma EEG events as a trigger for ensuing changes to the directional
      derivative of signals across the EEG montage. RESULTS: The INRI had a positive
      relationship with GCS and was significantly different between various levels of
      consciousness. In comparison, classical band-limited power analysis did not show
      any specific patterns correlated to GCS. CONCLUSIONS: These findings suggest that
      reaching low variance EEG activation patterns becomes progressively harder as the
      level of consciousness of patients deteriorate, and provide a quantitative index
      based on passive measurements that characterize this change. SIGNIFICANCE: Our
      results emphasize the role of intrinsic brain dynamics in assessing the level of
      consciousness in coma patients and the possibility of employing simple
      electrophysiological measures to recognize the severity of disorders of
      consciousness (DOC).

PMID- 30240979
TI  - The associations between subdimensions of religiosity and illicit substance use
      among latino sexual minority men.
AB  - BACKGROUND: Latino sexual minority men (SMM) may be a group disproportionately at
      risk for substance use than heterosexual Latino men and non-Latino SMM. As
      religiosity may be a culturally relevant factor, the current study aimed to
      explore the association of three subcomponents of religiosity: organizational
      religious activity (ORA; i.e., public religious activity), non-organizational
      religious activity (NORA; i.e., private religious activity), and intrinsic
      religiosity (IR; i.e., personal commitment to one's religion) in predicting
      illicit substance use. METHOD: Participants were 151 Latino SMM recruited from
      San Diego County (M = 24.18 years of age, SD = 3.19), who completed online self
      report questionnaires in English or Spanish. Binary outcome variables represented
      use of illicit substances in the past month vs. no use. Religiosity was assessed
      using the three subscales (ORA, NORA, and IR) of the Duke University Religion
      Index (DUREL). Acculturation was controlled for using the Bidimensional
      Acculturation Scale for Hispanics. RESULTS: ORA was associated with opiates (OR =
      1.53, p = .04). NORA was associated with cocaine (OR = 1.69, p = .01), opiates
      (OR = 1.56, p = .04), amphetamines (OR = 1.67, p = .02), and sedatives (OR =
      2.33, p = .001). IR was associated with amphetamines (OR = 1.34, p = .03).
      CONCLUSION: NORA is positively associated with multiple illicit substances, and
      may represent greater internalization of anti-gay religious doctrines compared to
      other components of religiosity in Latino SMM. An intersectional approach
      addressing religious and sexual minority identity may be useful in substance use
      treatment for Latino SMM.

PMID- 30240980
TI  - Effects of acute stress on social behavior in women.
AB  - Acute stress is known to increase prosocial behavior in men via a "tend-and
      befriend" pattern originally proposed as a specifically female stress response
      alongside the fight-or-flight response. However, the direct effects of acute
      stress on women's social behavior have not been investigated. Applying the Trier
      Social Stress Test for groups (TSST-G), 94 women were confronted with either a
      stress or control condition. We repeatedly measured their subjective stress
      responses, salivary cortisol, and heart rate, and investigated their level of
      trust, trustworthiness, sharing, punishment and non-social risk using social
      decision paradigms. We detected significant increases in all stress parameters,
      as well as the wish for closeness during the stress condition. Acute stress
      exposure elevated prosocial trustworthiness and sharing without affecting non
      social risk behavior. These results are in line with findings on the effects of
      stress in men, and further validate the tend-and-befriend pattern as one possible
      behavioral response during stress in humans.

PMID- 30240981
TI  - Towards accurate infrared spectral density of weak H-bonds in absence of
      relaxation mechanisms.
AB  - Following the previous theoretical developments to completely reproduce the IR
      spectra of weak hydrogen bond complexes within the framework of the linear
      response theory (LRT), the quantum theory of the high stretching mode spectral
      density (SD) of weak H-bonds is reconsidered. Within the LRT theory, the SD is
      the one sided Fourier transform of the autocorrelation function (ACF) of the high
      stretching mode dipole moment operator. In order to provide more accurate
      theoretical bandshapes, we have explored the equivalence between the SDs given in
      previous studies with respect to a new quantum one, and revealed that in place of
      the basic equations used in the precedent works for which the SD
      IOld(omega)=2Re?0infinityGOld(t)e-iomegatdt where the ACF GOld(t) = ?MU(0)MU(t)+?
      = tr {rho {MU(0)} {MU(t)}+}, one can use a new expression for the SD, given by
      INew(omega)=2omegaRe?0infinityGNew(t)e-iomegatdt where
      GNew(t)=MU(0)MU(t)+=1betatrrhoB?0betaMU(0)MU(t+ilambdah)+dlambda. Here rhoB is
      the Boltzmann density operator, MU(0) the dipole moment operator at initial time
      and MU(t) the dipole moment operator at time t in the Heisenberg picture, h is
      the Planck constant, beta is the inverse of the Boltzmann factor kBT where T is
      the absolute temperature and kB the Boltzmann constant. Using this formalism, we
      demonstrated that the new quantum approach gives the same final SD as used by
      previous models, and reduces to the Franck-Condon progression appearing in the
      Marechal and Witkowski's pioneering approach when the relaxation mechanisms are
      ignored. Results of this approach shed light on the equivalence between the
      quantum and classical IR SD approaches for weak H-bonds in absence of medium
      surroundings effect, which has been a subject of debate for decades.

PMID- 30240982
TI  - Asymmetric substitution changes the UV-induced nonradiative decay pathway and the
      spectra behaviors of beta-diketones.
AB  - Asymmetric substitution has not been termed as an essential factor in studying
      photo-induced ultrafast dynamics of molecular system. Asymmetric 4-hydroxybut-3
      en-2-one (HEO), together with symmetric malonaldehyde (MA) and acetylacetone
      (AA), have been provided as target sample to study the nonradiative decay (ND)
      processes of beta-diketones. An effective ND pathway of the three molecules is
      presented that their excited second (S2) states transfer to first (S1) state by
      nonadiabatic surface hopping, and then transfer to triplet (T1) state by crossing
      minimum energy crossing point (MECP), after which decay to ground (S0) state
      through MECP. More importantly, the asymmetric substitution of HEO induces the
      proton transfer in the S1 state and generates a proton-transferred conformer with
      lowest energy, which does not occur for MA and AA. This change exploits a new ND
      pathway that the S1 state decays to the proton transferred T1 state and then
      undergoes reverse proton transfer to S0 state through the MECPs between the three
      states. The two pathways of HEO give detailed energy and geometric information on
      surface hopping of S2/S1 and MECPs of S1/T1/S0, and interpret the reason of the
      ND pathway while not spectra emission. This result is significantly different
      from the previous reported ND pathway of photoisomerization or conical
      intersection between different states. This work shows that asymmetric
      substitution changes the molecular structure and then changes their spectra
      behaviors.

PMID- 30240983
TI  - X-ray irradiation inactivation of Escherichia coli O157:H7, Salmonella enterica
      Serovar Typhimurium, and Listeria monocytogenes on sliced cheese and its
      bactericidal mechanisms.
AB  - In the last two decades several foodborne disease outbreaks associated with
      cheese products were reported. The objective of this study was to investigate the
      efficacy of X-ray irradiation for the inactivation of foodborne pathogens on
      sliced cheese and to elucidate the underlying mechanisms of the lethal effect. In
      addition, the effect of the X-ray irradiation on product quality was determined.
      A mixed culture containing Escherichia coli O157:H7, Salmonella Typhimurium, and
      Listeria monocytogenes was inoculated on the surfaces of cheese slices. The
      inoculated samples were re-packaged and treated with 0, 0.2, 0.4, 0.6, and 0.8
      kGy of X-ray radiation. Approximately 5 log reductions in the viability of the
      three pathogens on samples were achieved at an irradiation dose of 0.6 kGy.
      Furthermore, the color values (L*, a*, and b*) and texture parameters of sliced
      cheeses were not altered significantly (all P > 0.05) after treatment at the
      maximum dose of 0.8 kGy. Various fluorescence staining methods were utilized to
      analyze the bactericidal mechanisms. The analyses confirmed that levels of
      depolarization of cell membranes, generation of reactive oxygen species, and
      intracellular enzyme inactivation were strongly related to the trends of
      microbial inactivation. The results of the present study suggest that X-ray
      irradiation may be an innovative antimicrobial intervention for various post
      packaged dairy food products.

PMID- 30240984
TI  - Using Torulaspora delbrueckii killer yeasts in the elaboration of base wine and
      traditional sparkling wine.
AB  - For still wines, killer strains of Torulaspora delbrueckii can be used instead of
      non-killer strains to improve this species' domination during must fermentation,
      with an ensured, reliable impact on the final wine quality. The present work
      analysed the usefulness of these killer yeasts for sparkling-wine making. After
      the first fermentation, the foaming capacity of T. delbrueckii base wines was
      very low compared to Saccharomyces cerevisiae base wines. Significant positive
      correlations of foaming parameters were found with the amounts of C4-C16 ethyl
      esters and proteins, and negative with some anti-foaming alcohols produced by
      each yeast species. There were, however, no evident positive effects of
      polysaccharides on those parameters. The organoleptic quality of the T.
      delbrueckii base wines was judged inappropriate for sparkling-wine making, so
      that the following second-fermentation experiments only used a single assemblage
      of S. cerevisiae base-wines. While second fermentation was completed with
      inoculation of S. cerevisiae (both alone and mixed with T. delbrueckii) to yield
      dry sparkling wines with high CO2 pressure, single inoculation with T.
      delbrueckii did not complete this fermentation, leaving sweet wines with poor CO2
      pressure. Yeast death due to CO2 pressure was much greater in T. delbrueckii than
      in S. cerevisiae, making any killer effect of S. cerevisiae over T. delbrueckii
      irrelevant because no autolysed cells were found during the first days of mixed
      inoculated second fermentation. Nonetheless, the organoleptic quality of the
      mixed-inoculated sparkling wines was better than that of wines single-inoculated
      with S. cerevisiae, and showed no deterioration in foam quality. This seemed
      mainly to be because T. delbrueckii increased the amounts of ethyl propanoate and
      some acids (e.g., isobutyric and butanoic), alcohols (e.g., 3-ethoxy-1-propanol),
      and phenols (e.g., 4-vinylguaiacol). For these sparkling wines, no significant
      correlations between foaming parameters and aroma compounds were found, probably
      because the differences in foaming parameter values among these wines were fairly
      small. This is unlike the case for the base wines for which there were large
      differences in these parameters, which facilitated the analysis of the influence
      of aroma compounds on base-wine foamability.

PMID- 30240985
TI  - In-silico screening of small molecule inhibitors against Lactate Dehydrogenase
      (LDH) of Cryptosporidium parvum.
AB  - Cryptosporidium parvum is a protozoan parasite which causes waterborne diseases
      known as Cryptosporidiosis. It is an acute enteric diarrheal disease being severe
      in the case of immunocompromised individuals and children. C. parvum mainly
      depends on the glycolysis process for energy production and LDH (Lactate
      Dehydrogenase) is a key controller of this process. In this study from different
      in-silico approaches such as structure-based, ligand-based and de novo drug
      design; a total of 40 compounds were selected for docking studies against LDH.
      The study reported a compound CHEMBL1784973 from Pathogen Box as the best
      inhibitor in terms of docking score and pharmacophoric features. Furthermore, the
      binding mode of the best-reported inhibitor was validated through molecular
      dynamics simulation for a time interval of 70 ns in water environment. The
      findings resulted in the stable conformation of the inhibitor in the active site
      of the protein. This study will be helpful for experimental validation.

PMID- 30240986
TI  - Discovery of natural product inhibitors of phosphodiesterase 10A as novel
      therapeutic drug for schizophrenia using a multistep virtual screening.
AB  - The major complaint that most of the schizophrenic patients' face is the
      cognitive impairment which affects the patient's quality of life. The current
      antipsychotic drugs treat only the positive symptoms without alleviating the
      negative or cognitive symptoms of the disease. In addition, the existing
      therapies are known to produce extrapyramidal side effects that affect the
      patient adherence to the treatment. PDE10A inhibitor is the new therapeutic
      approach which has been proven to be effective in alleviating the negative and
      cognitive symptoms of the disease. A number of PDE10A inhibitors have been
      developed, but no inhibitor has made it beyond the clinical trials so far. Thus,
      the present study has been conducted to identify a PDE10A inhibitor from natural
      sources to be used as a lead compound for the designing of novel selective PDE10A
      inhibitors. Ligand and structure-based pharmacophore models for PDE10A inhibitors
      were generated and employed for virtual screening of universal natural products
      database. From the virtual screening results, 37 compounds were docked into the
      active site of the PDE10A. Out of 37 compounds, three inhibitors showed the
      highest affinity for PDE10A where UNPD216549 showed the lowest binding energy and
      has been chosen as starting point for designing of novel PDE10A inhibitors. The
      structure-activity-relationship studies assisted in designing of selective PDE10A
      inhibitors. The optimization of the substituents on the phenyl ring resulted in
      26 derivatives with lower binding energy with PDE10A as compared to the lead
      compound. Among these, MA 8 and MA 98 exhibited the highest affinity for PDE10A
      with binding energy (-10.90 Kcal/mol).

PMID- 30240987
TI  - Comparison of in vitro/in vivo blood distribution and pharmacokinetics of
      artemisinin, artemether and dihydroartemisinin in rats.
AB  - Artemisinin and its derivatives have been widely used for treatment of malaria
      and the therapeutic targets are considered within the red blood cells. In the
      recent studies on the erythrocytes' uptake of artemisinin-derivatives in vitro,
      applying the radioisotope-labeled technology, it was trying to predict the in
      vivo disposition properties, but different distribution results were revealed
      from a preliminary study in one human. The pharmacokinetic differences among
      blood cells and plasma still remain unclear. To explore the therapeutic related
      pharmacokinetics and compare the in vitro-in vivo blood distribution in rats, an
      improving blood sample preparation and LC-MS/MS detection method was developed
      and successfully validated. The lower limit of quantification was smaller than
      the previous studies. In the in vitro blood distribution studies, the content
      ratios from blood cells to plasma were compared in the concentrations from 20
      ng/mL to 1000 ng/mL. Such ratios were determined to be 1.1-1.6 for artemisinin,
      0.9-1.2 for artemether, and around 0.7 for dihydroartemisinin. In the oral
      administration pharmacokinetic studies in rats, the concentration ratios from
      blood cells to plasma were from high (2.6-3.6) to medium (1.3-2.5), and low (0.5
      1.5) for artemisinin, artemether, and dihydroartemisinin respectively in all
      measuring time points, displaying the similar affinity order toward blood cells
      in artemisinin > artemether > dihydroartemisinin as the in vitro measurements.
      The dosages of 10 mg/kg for intravenous administrations of artemisinin and 200
      mg/kg for oral administrations of artemisinin or artemether were used for the
      pharmacokinetic study in rats. The geometric mean exposures (AUC(0-t)) of
      artemisinin, artemether and dihydroartemisinin in blood cells were determined to
      be 2.6 folds, 1.7 folds, or 1.2 folds greater than those in plasma, respectively.
      Referring to the in vitro distribution, the AUC(0-t) ratios from the blood cells
      measurements to the plasma measurements of these three antimalarial drugs were
      also in a similar trend as the in vitro distribution measurements. Furthermore,
      the half-life (t1/2) of artemether in blood cells was even longer than that in
      plasma, while the clearance of artemisinin, artemether, or dihydroartemisinin in
      blood cells was slower than that in plasma. Particularly, it was found that the
      concentrations of artemisinin and artemether were presented in blood cells over
      longer time period than in plasma above their antimalarial IC50, which might
      result from both the affinity toward blood cells and the drugs clearance
      differences between blood cells and plasma. These results were indicated that the
      exposures and pharmacokinetic properties in the whole blood or the blood cells
      should be taken into account for the drug candidates with higher distribution
      affinity toward blood cells especially for the antimalarial drugs.

PMID- 30240988
TI  - Precision of the reportable value-Statistical optimization of the number of
      replicates.
AB  - In pharmaceutical analysis, the precision of the reportable value, i.e. the
      result which is to be compared to the specification limit(s), is relevant for the
      suitability of the analytical procedure. Using the variance contributions
      determined in precision studies addressing the levels injection/system precision,
      repeatability, and intermediate precision, the number of the corresponding
      replications for analysis/injection, sample preparation, and series/runs can be
      varied to improve the precision of the mean (reportable) value (Ermer, Agut,
      J.Chromatogr. A, 1353 (2014) 71-77). However, this calculation will provide only
      information on the gain for the precision of the calculated reportable value
      itself. These so-called point estimators have uncertainty associated with them
      which can be quantified using statistical confidence intervals. Commonly used
      statistical equations only allow one to calculate confidence intervals for the
      intermediate precision of the reportable value, which requires that the routine
      replication strategy must be defined before starting the precision study. In this
      paper, statistical models are presented that allow optimizing efficiently the
      replication strategy with respect to the confidence interval of the precision
      based on the Satterthwaite approximation posterior, i.e. using the results from
      the precision study without prior knowledge, as for the point estimate. It is
      further proposed to simplify the model by including only significant variance
      contributions larger than 20% of the total variation. The advantage of this
      minimizing the level of nesting is that the upper precision bound will tighten as
      the level of nesting decreases. This is important as 90% upper confidence bounds
      are often up to 2 or 3 times the point estimate, even for a larger number of four
      runs in the precision study. Four models each have been developed both for a 2
      fold balanced nested design representing a complete intermediate precision study,
      and for a 1-fold balanced nested design using injection/system precision from an
      independent source. An Excel spreadsheet that performs all the calculations in
      this paper as well as the appropriate model selection is available from the
      authors. Due to the usually rather low number of series/runs in precision
      studies, the uncertainty of the reportable value precision is often dominated by
      the factor runs. For a statistical evaluation of the precision of the reportable
      value (in case of three precision levels), the authors recommend a minimum of six
      runs, two preparations per run, and two injections/analyses per preparation, in
      order to provide sufficient precision of the variance estimates. However, a risk
      based approach is recommended for the decision to apply a statistical evaluation
      of the precision of the reportable value. In case of low patient risk such as for
      an assay of a well-characterized drug substance with tightly controlled
      manufacturing and analytical variability dominating the specification range, a
      point estimator will usually be adequate to demonstrate the suitability of the
      analytical procedure.

PMID- 30240990
TI  - Cloning of the full-length isoamylase3 gene from cassava Manihot esculenta Crantz
      'KU50' and its heterologous expression in E. coli.
AB  - Isoamylase (EC.3.2.1.68), an essential enzyme in starch metabolism, catalyses the
      cleavage of alpha-1,6 glucosidic linkages of branched alpha-polyglucans such as
      beta-limit dextrin and amylopectin, but not pullulan. Three different isoamylase
      isoforms have been reported in plants and algae. We herein report on the first
      success in preparation of full-length isoamylase3 gene (MeISA3) of cassava
      Manihot esculenta Crantz 'KU50' from 5' Rapid Amplification of cDNA Ends (5'
      RACE). The MeISA3 was cloned to pET21b and expressed in E. coli. The HistrapTM
      purified rMeISA3 appeared as a single band protein with approximate molecular
      size of 75 kDa on SDS-PAGE and Western blot, while 80 kDa was shown by gel
      filtration chromatography. This indicated the existence of a monomeric enzyme.
      Biochemical characterisation of rMeISA3 showed that the enzyme was specific
      towards beta-limit dextrin, with optimal activity at 37  degrees C pH 6.0.
      Activity of rMeISA3 could be significantly promoted by Mg2+ and Co2+. rMeISA3
      debranched glucan chains of amylopectin were confirmed by HPAEC-PAD analysis.

PMID- 30240991
TI  - Patient-ventilator interaction with conventional and automated management of
      pressure support during difficult weaning from mechanical ventilation.
AB  - PURPOSE: Optimizing pressure support ventilation (PSV) can improve patient
      ventilator interaction. We conducted a two-center, randomized cross-over study to
      determine whether automated PSV lowers asynchrony rate during difficult weaning
      from mechanical ventilation. METHODS: Thirty patients failing the first weaning
      attempt were randomly ventilated for 2 three-hour consecutive periods with: 1)PSV
      managed by physicians (convPSV); 2)PSV managed by Smartcare(r) (autoPSV). These 2
      periods were applied in the afternoon and overnight, for a 12-h total study time.
      Two independent clinicians offline analyzed ventilator waveforms to compute
      asynchrony index(AI). RESULTS: AI was lower during autoPSV than during convPSV
      (medians[interquartile ranges] 5.1[2.6-9.5]% vs. 7.3[2.3-13.4]%, p = 0.02),
      without changes in the proportion of patients with AI>10%(p = 0.31). Pressure
      support (PS) variability was higher during autoPSV (p < 0.001), but average PS
      did not vary. In patients with baseline PS > 12 cmH2O (n = 15), PS and tidal
      volume were lower with autoPSV (12 [10-15]cmH2O vs. 15 [14-18]cmH2O,p = 0.003;
      7.2[6.2-8.3]ml/Kg vs. 8.2[7.1-9.1]ml/Kg, p = 0.02) and AI reduction was driven by
      lower tidal volume (p = 0.03). In patients with baseline PS <= 12 cmH2O, AI
      reduction during autoPSV was mediated by increased PS variability (p = 0.04).
      CONCLUSION: During difficult weaning, autoPSV improves patient-ventilator
      interaction by lowering tidal volume and enhancing PS variability. In expert
      centres, however, the size effect of the intervention appears clinically small,
      likely because physicians themselves adequately limit PS and tidal volume.

PMID- 30240992
TI  - Impacts of heavy metals and soil properties at a Nigerian e-waste site on soil
      microbial community.
AB  - Heavy metal contamination is a serious problem worldwide threatening soil
      environment and human health. In the present study, concentrations of 6 heavy
      metals at an electronic waste (e-waste) site in Nigeria were correlated to their
      mobility, showing distinct distribution pattern between surface soils and
      subsoils. Proteobacteria, Firmicutes, Acidobacteria and Planctomycetes dominated
      the indigenous soil microbial communities, and there was significant
      discrimination of bacterial taxonomic composition between the heavy metal
      contaminated and uncontaminated areas. The abundance of most bacterial taxa
      changed with heavy metal contamination level to different extent. The
      multivariate regression tree (MRT) analyses illustrated that main environmental
      variables influencing bacterial taxonomic composition included soil texture (31%)
      and organic carbon (14%), whereas microbial diversity was affected by soil pH
      (32%) and soil texture (14%). Our results surprisingly indicated that soil
      properties were more influential in determining soil bacterial composition and
      diversity than heavy metals even at the e-waste site which was seriously
      contaminated by heavy metals. The present study contributes to a deeper insight
      into the key environmental variables shaping the diversity and composition of
      soil microbes at heavy metal contaminated e-waste sites.

PMID- 30240989
TI  - The effects of salicylic acid and glucose on biochemical traits and taxane
      production in a Taxus baccata callus culture.
AB  - The combined use of elicitors can be an effective way to increase the production
      of secondary metabolites (SMs) in plant cell, tissue and organ cultures. This
      study investigated the effects of a salicylic acid (SA) pretreatment and
      different glucose levels on the growth, biochemical traits and taxane production
      in a Taxus baccata callus culture. For this purpose, after a pretreatment with SA
      (5 MUM), three-month-old calli were cultured on B5 medium fortified with
      different concentrations of glucose (0, 0.5, 1, 2 and 3%), and they were compared
      with calli cultured on a B5 medium supplemented only with glucose. When the calli
      were harvested at 21 days, their fresh weight (g), dry weight (g) and cell
      viability (%) had decreased significantly (p < 0.05) with the higher glucose
      concentrations. The glucose treatment increased the hydrogen peroxide (H2O2) and
      malondialdehyde (MDA) content, and caused oxidative stress in treated tissues.
      The lower H2O2 content and oxidative stress was associated with an increased
      antioxidant enzyme activity in the SA-pretreated samples, which resulted in less
      membrane damage and improved growth and cell viability under the glucose
      treatment compared to the control. By reducing the activity of phenylalanine
      ammonia-lyase (PAL) and polyphenol oxidase (PPO), the SA pretreatment reduced the
      production and oxidation of phenolic compounds under the glucose treatment; this
      decrease was associated with less browning of tissues and higher viability.
      Increases in taxol (5.1-fold) and total taxanes (3.5-fold) in the SA-pretreated
      calli cultured on the medium containing 2% glucose, compared to the control,
      indicated that the two treatments had a significant effect on taxane production
      in the T. baccata callus culture.

PMID- 30240993
TI  - Polyaluminum chloride-functionalized colloidal gas aphrons for flotation
      separation of nanoparticles from water.
AB  - The present work used the coagulative colloidal gas aphron (CCGA)-involved
      flotation as a robust technology to efficiently remove the typical engineered
      nanoparticles - silica nanoparticles (SNPs) from water. The inorganic polymer
      coagulant - polyaluminum chloride (PACl) was used to surface-functionalize the
      zwitterionic surfactant (C15B)-based CGAs. Results denote that the
      physicochemical conditions of PACl/C15B mixed solution markedly influenced the
      flotation behaviors by changing the properties of CCGAs. The C15B molecules
      showed different dissociated states and interaction behaviors with Al species
      with the variation of pH. The addition of salt into the PACl/C15B mixed solution
      decreased the foamability of solution, and the bubbles collapsed before they
      could efficiently capture SNPs in their rising trajectory. The optimum SNP
      removal (87.2%) was obtained when the pH and the additional ionic strength of
      PACl/C15B mixed solution were ~4.7 and <= 1.0 g NaCl/L, individually, and the pH
      of SNP suspension was ~9.4. Importantly, modifying PACl on microbubbles took
      greater advantages than directly using it as coagulant in terms of SNP removal
      and PACl utlization. The CCGAs were robust since their colloidal attraction and
      collision efficiency with SNPs were simultaneously enhanced. The PACl was more
      efficiently utilized during flotation whilst the regular chemical-dosing unit was
      omitted.

PMID- 30240994
TI  - beta-cyclodextrin functionalized biochars as novel sorbents for high-performance
      of Pb2+ removal.
AB  - The aim of this study was to synthesize the functionalized biochars with beta
      cyclodextrin (beta-CD), compare the two kinds of adsorption capability, and try
      to explore the possible mechanism for the adsorption Pb2+ by beta-CD
      functionalized rice straw and palm biochars in the aquatic environment. The
      performance of the functionalized biochars was matched against the activated and
      raw biochars. Rice straw biochar loaded with beta-CD performed better than
      functionalized palm biochar with the adsorption capabilities of 130.60 mg/g and
      90.30 mg/g at Pb2+ concentration of 3000 mg/L and 2000 mg/L, respectively.
      Maximum adsorption capability of functionalized rice straw and palm biochars from
      the Langmuir isotherms were all fitted out to be 131.24 mg/g and 118.08 mg/g for
      Pb2+. Kinetics and thermodynamics are combined to investigate the Pb2+ removal by
      the two functionalized biochars, e.g, Pb2+ is mainly removed by chemical process
      for functionalized palm biochar, whereas by both physical and chemical factors
      for functionalized rice straw biochar.

PMID- 30240995
TI  - Formation of environmentally persistent free radicals during the transformation
      of anthracene in different soils: Roles of soil characteristics and ambient
      conditions.
AB  - Transformation of PAHs, i.e., anthracene, and production of environmentally
      persistent free radicals (EPFRs) on seven types of representative soils were
      investigated, focusing on the influences of soil characteristics and ambient
      conditions on these reactions. The transformation rate of anthracene exhibits the
      order of red earth > yellow earth > latosol ~ fluvo-aquic soil > brown earth >
      chernozem > calcic brown soil, which is positively correlated with Fe content in
      soils. Afterwards, batch reactions on pure representatives of soil minerals,
      including Fe2O3, Fe3O4, FeOOH, and MnO2, demonstrate that anthracene is prone to
      mineral-promoted transformation. The presence of higher amount of organic carbon
      lower the transformation rate of anthracene, whereas the formed EPFRs can be
      stabilized for a longer time. Subsequent experiments associated with the
      influences of environmental conditions on mineral-promoted reactions suggest that
      both anthracene transformation and EPFRs generation readily occur under dry
      condition. Light irradiation not only promotes the formation of EPFRs, but also
      greatly accelerates the decay of EPFRs and the 1/e lifetime decreases from 5 to
      20 d in dark to approximately 1 d. Meanwhile, the anoxic condition is favorable
      for the persistence of EPFRs. The obtained results suggested the potential
      environmental risks association with EPFRs in PAHs-contaminated soils.

PMID- 30240996
TI  - The effect of ultra-low temperature on the flammability limits of a
      methane/air/diluent mixtures.
AB  - Natural gas represents an attractive fuel for industrialized and developing
      countries seeking an alternative to petroleum. Due to economic and safety
      considerations, liquefied natural gas (LNG) at cryogenic conditions is preferred
      for storage and transportation. The main drawback is the poor understanding of
      the physical and chemical phenomena that occur at the storage conditions of
      liquid methane, i.e. at ultra-low temperatures around 110 K and, if released, at
      temperatures below ambient. In this work, a procedure to evaluate the laminar
      burning velocity, the flammability limit (FL) and the limiting oxygen
      concentration (LOC) of methane-air-diluent mixtures based on detailed kinetic
      mechanism at ultra-low temperatures is proposed. The estimation of the FL was
      obtained with the limiting burning velocity theory. The effects of inert content
      (extinguishing) and agent (N2, H2O and CO2) on FL were evaluated and compared
      with data retrieved from the literature. The agreement between experimental
      observation and model results from 200 K-300 K incentivizes the adoption of the
      new procedure for further studies of fuel reactivity and safety parameters.
      Moreover, the proposed procedure may be suitable for the estimation of the safety
      parameters of complex fuel mixtures whose composition is closer to the actual
      values of LNG.

PMID- 30240997
TI  - Calibration and application of passive sampling for per- and polyfluoroalkyl
      substances in a drinking water treatment plant.
AB  - The aim of this study was to calibrate and apply polar organic chemical
      integrative samplers (POCIS) to examine 26 per- and polyfluoroalkyl substances
      (PFASs) in a drinking water treatment plant (DWTP). As a first step, the sampling
      rates (Rs) of 14 PFASs were determined in a laboratory calibration study for
      POCIS-WAX (weak-anion exchange) and POCIS-HLB (hydrophilic-lipophilic balance)
      (each with a surface area per mass of sorbent ratio of 227 cm2 g-1). While most
      PFASs were still in the linear uptake phase during the 28-day calibration study,
      Rs ranged from 0.003 to 0.10 L d-1 for POCIS-WAX and 0.00052 to 0.13 for POCIS
      HLB. It is important to note that POCIS-WAX had higher Rs for short-chain
      perfluoroalkyl carboxylates (PFCAs) with a perfluorocarbon chain length of C3-C6
      and perfluorobutane sulfonate (PFBS) compared with POCIS-HLB. Furthermore, Rs was
      significantly positively correlated with the sorbent-water partition coefficient
      (Kpw) for POCIS-WAX and POCIS-HLB (p < 0.0001). Use of POCIS-WAX and POCIS-HLB in
      the DWTP showed good agreement with composite water sampling. No removal of PFASs
      was observed in the full-scale DWTP. Overall, this is the first study of PFAS
      monitoring in a DWTP using two types of POCIS. The results demonstrate high
      suitability for future applications.

PMID- 30240998
TI  - Removal of micropollutants from water in a continuous-flow electrical discharge
      reactor.
AB  - The emergence of micropollutants into our aquatic resources is regarded as an
      issue of increasing environmental concern. To protect the aquatic environment
      against further contamination with micropollutants, treatment with advanced
      oxidation processes (AOPs) is put forward as a promising technique. In this work,
      an innovative AOP based on electrical discharges in a continuous-flow pulsed
      dielectric barrier discharge (DBD) reactor with falling water film over activated
      carbon textile is examined for its potential application in water treatment. The
      effect of various operational parameters including feed gas type, gas flow rate,
      water flow rate and power on removal and energy efficiency has been studied. To
      this end, a synthetic micropollutant mixture containing five pesticides
      (atrazine, alachlor, diuron, dichlorvos and pentachlorophenol), two
      pharmaceuticals (carbamazepine and 1,7-alpha-ethinylestradiol), and 1 plasticizer
      (bisphenol A) is used. While working under optimal conditions, energy consumption
      was situated in the range 2.42-4.25 kW h/m3, which is about two times lower than
      the economically viable energy cost of AOPs (5 kW h/m3). Hence, the application
      of non-thermal plasma could be regarded as a promising alternative AOP for
      (industrial) wastewater remediation.

PMID- 30240999
TI  - Simultaneous cationic Cu (II)-anionic Sb (III) removal by NH2-Fe3O4-NTA core
      shell magnetic nanoparticle sorbents synthesized via a facile one-pot approach.
AB  - In this study, a regenerable magnetic core-shell nanoparticles NH2-Fe3O4-NTA
      which include 3-aminopropyltriethoxysilane (APTES) and nitrilotriacetic acid
      (NTA) crosslinked to Fe3O4 was developed by one-pot method for simultaneous
      removal of cationic and anionic metals. Another nanocomposite NH2-Fe3O4-NTAII was
      prepared by multi-step method for comparison. NH2-Fe3O4-NTA had positive zeta
      potential values of 35.1-0.8 mV at pH 1.8-11.0, with the saturation magnetization
      and surface area up to 40.56 emu/g and 56.94 m2/g, respectively. The maximum
      sorption capacities of NH2-Fe3O4-NTA for cationic Cu (II) and anionic Sb (III)
      were 55.56 and 51.07 mg/L, respectively, which were superior to that of NH2-Fe3O4
      NTAII. Based on screening in terms of characterization and metal sorption
      capacity, NH2-Fe3O4-NTA with a feasible synthesis scheme was chosen for further
      evaluation. The Cu (II) removal by NH2-Fe3O4-NTA was favored with increasing pH,
      while the Sb (III) removal preferred low pH (2-3). Simultaneous sorption of Cu
      (II) and Sb (III) exhibited same removal performance with the sole sorption under
      high dosage (>1 g/L). In real wastewater applications of NH2-Fe3O4-NTA, multiple
      metals in actual wastewater could be removed to well below the regulation levels.
      Nonspecific electrostatic interactions, inner-sphere complexation, ligand
      exchange, chelation and coordination complexation were responsible for Cu (II)
      and Sb (III) removal.

PMID- 30241000
TI  - New animal model of extrinsic dental erosion-Erosive effect on the mouse molar
      teeth.
AB  - OBJECTIVE: Consumption of acidic food and drinks is considered as important risk
      factor for development of dental erosion. There are several in vitro and in situ
      studies focusing on the risk indicators and preventive treatment, however, the
      need for a standardized animal model has been emphasised for many years. The aim
      was to establish an animal model of extrinsic dental erosion, which may serve as
      a standard for future studies to improve our understanding of the erosion.
      DESIGN: Two acidic drinks, sports drink and cola drink, were given to young mice
      for six weeks. Experimental and control (water) molars and incisors were
      dissected out and observed by scanning electron microscopy (SEM). Mandibular
      first molars were subsequently ground transversely and observed again by SEM. The
      tooth height and enamel thickness were measured on the SEM images. RESULTS: The
      lingual surface of the mandibular molars was most eroded after consumption of
      acidic drinks. The cola drink exhibited higher erosive effect on mandibular
      molars compared to sports drink. The lingual tooth height, compared to control,
      was about 34% and 18% lower in the cola drink and sports drink molars,
      respectively. Compared to the control molars, the lingual enamel was about 23%
      thinner in the sports drink molars and totally eroded on the certain lingual
      areas of the cola drink molars. CONCLUSIONS: This new animal model of extrinsic
      dental erosion and the presented method with ground molars observed in SEM are
      suitable for further studies, which will gain deeper insights into the erosive
      disease.

PMID- 30241001
TI  - Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal,
      hormone receptor-positive, human epidermal growth factor receptor 2-negative,
      advanced breast cancer: Overall survival results from BELLE-2.
AB  - BACKGROUND: Buparlisib, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor,
      plus fulvestrant in the BELLE-2 study significantly improved progression-free
      survival (PFS) in patients with hormone receptor-positive, human epidermal growth
      factor receptor 2-negative advanced breast cancer. PATIENTS AND METHODS: In this
      phase III study, patients were randomised 1:1 to buparlisib (100 mg/day;
      continuously in 28-day cycles) or placebo, plus fulvestrant (500 mg on cycle 1
      day 15, and day 1 of subsequent cycles). Overall survival (OS) was assessed in
      the overall population and patients with known PI3K pathway status (both had
      shown significant PFS improvements). OS by PIK3CA status in circulating tumour
      DNA (ctDNA) was an exploratory end-point. RESULTS: A total of 2025 patients were
      screened for eligibility between 7th September 2012 and 10th September 2014, and
      1178 received fulvestrant (500 mg) during a run-in phase; 31 discontinued. Of
      1147 patients (median age 62 years), 98% had the Eastern Cooperative Oncology
      Group performance status <=1, and 59% had visceral disease. Median follow-up from
      randomisation to data cut-off (23rd December 2016) was 37.6 months. Median OS
      trended in favour of the buparlisib arm in the overall population (33.2 versus
      30.4 months; P = 0.045) and among patients with known PI3K pathway status (30.9
      versus 28.9 months; P = 0.144); neither outcome was statistically significant.
      Median OS also trended in favour of buparlisib among patients with PIK3CA-mutant
      ctDNA (26.0 versus 24.8 months). Grade III/IV adverse events with >=10%
      difference between the buparlisib versus placebo arms were elevated alanine
      aminotransferase (26% versus 1%), elevated aspartate aminotransferase (18% versus
      3%) and hyperglycemia (15% versus <1%). CONCLUSIONS: OS results were in favour of
      buparlisib plus fulvestrant versus placebo plus fulvestrant; however, there is no
      statistical significance and more frequent grade III/IV adverse events were
      reported. Use of more selective PI3K inhibitors might provide the greatest
      clinical benefit and tolerable safety profile in this setting. Further evaluation
      of the predictive benefit of PIK3CA-mutant ctDNA is warranted. TRIAL REGISTRATION
      NUMBER: NCT01610284.

PMID- 30241002
TI  - Cancer Core Europe: A European cancer research alliance realizing a research
      infrastructure with critical mass and programmatic approach to cure cancer in the
      21st century.
AB  - Translational cancer research covers the whole cancer research continuum from
      basic to preclinical to early clinical, late clinical and outcomes research.
      Basic-preclinical research is the "engine" for early clinical research bridging
      the early translational research gap. Cancer Core Europe has been created to
      construct a sustainable, high level, shared research infrastructure platform with
      research collaborations and taskforces (data sharing, clinical trials, genomics,
      immunotherapy, imaging, legal & ethical problems, and education & training)
      having representatives from all seven member centres, in a controlled expansion
      model. In parallel, a consortium of ten cancer prevention centres was
      established, Cancer Prevention Europe, to support the complete cancer prevention
      research continuum. Cancer Core Europe is launching at present the Basket of
      Baskets trial, which is the largest personalized cancer medicine trial effort in
      Europe. At present, Cancer Core Europe and Cancer Prevention Europe are in the
      process of integrating therapeutics and prevention strategies to address in
      partnership the increasing cancer problem. By offering innovative approaches for
      cancer research, links to the healthcare systems, development of quality-assured
      multidisciplinary cancer care, as well as the assessment of long-term outcomes,
      the infrastructure is expected to serve as a hub to connect with other centres in
      Europe as well as on other continents. In this manner Cancer Core Europe and
      Cancer Prevention Europe prepare to tackle the "Mission on Cancer", with
      infrastructure and proofs of concept for therapeutics and prevention, research
      for assessment of effectiveness, health economics and added value for patients
      and the healthcare systems.

PMID- 30241003
TI  - Transgenerational effects of cyanobacterial toxins on a tropical micro-crustacean
      Daphnia lumholtzi across three generations.
AB  - Climate change and human activities induce an increased frequency and intensity
      of cyanobacterial blooms which could release toxins to aquatic ecosystems.
      Zooplankton communities belong to the first affected organisms, but in tropical
      freshwater ecosystems, this issue has yet been poorly investigated. We tested two
      questions (i) if the tropical Daphnia lumholtzi is capable to develop tolerance
      to an ecologically relevant concentration of purified microcystin-LR and
      microcystins from cyanobacterial extract transferable to F1 and F2 generations?
      And (ii) would F1 and F2 generations recover if reared in toxin-free medium? To
      answer these questions, we conducted two full factorial mutigenerational
      experiments, in which D. lumholtzi was exposed to MC-LR and cyanobacterial
      extract at the concentration of 1 MUg L-1 microcystin continuously for three
      generations. After each generation, each treatment was spit into two: one reared
      in the control (toxin free) while the other continued in the respective exposure.
      Fitness-related traits including survival, maturity age, body length, and
      fecundity of each D. lumholtzi generation were quantified. Though there were only
      some weak negative effects of the toxins on the first generation (F0), we found
      strong direct, accumulated and carried-over impacts of the toxins on life history
      traits of D. lumholtzi on the F1 and F2, including reductions of survival, and
      reproduction. The maturity age and body length showed some inconsistent patterns
      between generations and need further investigations. The survival, maturity age
      (for extract), and body length (for MC-LR) were only recovered when offspring
      from toxin exposed mothers were raised in clean medium for two generations.
      Chronic exposure to long lasting blooms, even at low density, evidently reduces
      survival of D. lumholtzi in tropical lakes and reservoirs with ecological
      consequences.

PMID- 30241004
TI  - Does the air pollution model influence the evidence of socio-economic disparities
      in exposure and susceptibility?
AB  - Studies assessing socio-economic disparities in air pollution exposure and
      susceptibility are usually based on a single air pollution model. A time
      stratified case-crossover study was designed to assess the impact of the type of
      model on differential exposure and on the differential susceptibility in the
      relationship between ozone exposure and daily mortality by socio-economic strata
      (SES) in Montreal. Non-accidental deaths along with deaths from cardiovascular
      and respiratory causes on the island of Montreal for the period 1991-2002 were
      included as cases. Daily ozone concentration estimates at partictaipants'
      residence were obtained from the five following air pollution models: Average
      value (AV), Nearest station model (NS), Inverse-distance weighting interpolation
      (IDW), Land-use regression model with back-extrapolation (LUR-BE) and Bayesian
      maximum entropy model combined with a land-use regression (BME-LUR). The
      prevalence of a low household income (< 20,000/year) was used as socio-economic
      variable, divided into two categories as a proxy for deprivation. Multivariable
      conditional logistic regressions were used considering 3-day average
      concentrations. Multiplicative and additive interactions (using Relative Excess
      Risk due to Interaction) as well as Cochran's tests were calculated and results
      were compared across the different air pollution models. Heterogeneity of
      susceptibility and exposure according to socio-economic status (SES) were found.
      Ratio of exposure across SES groups means ranged from 0.75 [0.74-0.76] to 1.01
      [1.00-1.02], respectively for the LUR-BE and the BME-LUR models. Ratio of
      mortality odds ratios ranged from 1.01 [0.96-1.05] to 1.02 [0.97-1.08],
      respectively for the IDW and LUR-BE models. Cochran's test of heterogeneity
      between the air pollution models showed important heterogeneity regarding the
      differential exposure by SES, but the air pollution model was not found to
      influence heterogeneity regarding the differential susceptibility. The study
      showed air pollution models can influence the assessment of disparities in
      exposure according to SES in Montreal but not that of disparities in
      susceptibility.

PMID- 30241005
TI  - Capturing the spatial variability of noise levels based on a short-term
      monitoring campaign and comparing noise surfaces against personal exposures
      collected through a panel study.
AB  - Environmental noise can cause important cardiovascular effects, stress and sleep
      disturbance. The development of appropriate methods to estimate noise exposure
      within a single urban area remains a challenging task, due to the presence of
      various transportation noise sources (road, rail, and aircraft). In this study,
      we developed a land-use regression (LUR) approach using a Generalized Additive
      Model (GAM) for LAeq (equivalent noise level) to capture the spatial variability
      of noise levels in Toronto, Canada. Four different model formulations were
      proposed based on continuous 20-min noise measurements at 92 sites and a leave
      one out cross-validation (LOOCV). Models where coefficients for variables
      considered as noise sources were forced to be positive, led to the development of
      more realistic exposure surfaces. Three different measures were used to assess
      the models; adjusted R2 (0.44-0.64), deviance (51-72%) and Akaike information
      criterion (AIC) (469.2-434.6). When comparing exposures derived from the four
      approaches to personal exposures from a panel study, we observed that all
      approaches performed very similarly, with values for the Fractional mean bias
      (FB), normalized mean square error (NMSE), and normalized absolute difference
      (NAD) very close to 0. Finally, we compared the noise surfaces with data
      collected from a previous campaign consisting of 1-week measurements at 200 fixed
      sites in Toronto and observed that the strongest correlations occurred between
      our predictions and measured noise levels along major roads and highway
      collectors. Our validation against long-term measurements and panel data
      demonstrates that manual modifications brought to the models were able to reduce
      bias in model predictions and achieve a wider range of exposures, comparable with
      measurement data.

PMID- 30241006
TI  - Steroids for familial acute necrotizing encephalopathy: A future investment?

PMID- 30241007
TI  - Clinical and magnetic resonance imaging predictors of the surgical outcomes of
      patients with cervical spondylotic myelopathy.
AB  - OBJECTIVE: To determine whether clinical characteristics and signal and
      morphologic changes on magnetic resonance (MR) images of the spinal cord (SC) are
      associated with surgical outcomes for cervical spondylotic myelopathy (CSM).
      PATIENTS AND METHODS: A total of 113 consecutive patients with cervical
      myelopathy underwent cervical decompression surgery in our hospital from January
      2015 to January 2018. All patients with preoperative MR images available for
      review were recruited for this study. Research data included patient sex, age,
      duration of symptoms, surgical approach, compression level, preoperative mJOA
      (modified Japanese Orthopaedic Association) score, postoperative mJOA recovery
      rate, and complications. Imaging data included signal changes on T2-weighted MRI
      images (grade and extension on sagittal images, four types of signal changes on
      axial images according to the Ax-CCM system), SC compression, transverse area of
      the SC, and compression ratio. The t-test, Mann-Whitney U-test, Kruskal-Wallis H 
      test, analysis of variance, and regression analysis were used to evaluate the
      effects of individual predictors on surgical outcomes. RESULTS: The study cohort
      included 85 males and 27 females with a mean age of 60.92 +/- 8.93 years. The
      mean mJOA score improved from 10.24 +/- 1.69 preoperatively to 15.11 +/- 2.05 at
      the final follow-up (p <  0.001). Patients in the poor outcome group were more
      likely to present with a longer duration of symptoms (p <  0.001) and smaller
      transverse area of the SC (p <  0.001). Bright T2-weighted high signal changes
      (T2HSCs), multisegmental high signal changes on sagittal MR images, and fuzzy
      focal T2HSCs on axial MR images were associated with a poor outcome (p < 0.001, p
      = 0.005, p <  0.001, respectively). The maximum SC compression and compression
      ratio were not reliable predictors of surgical outcomes (p =  0.375, p =  0.055,
      respectively). The result of multivariate stepwise logistic regression showed
      that a longer duration of symptoms, multisegmental T2HSCs on sagittal MR images
      and fuzzy focal T2HSCs on axial MR images were significant risk factors of poor
      outcomes (p < 0.001, p = 0.049, p =  0.016, respectively). CONCLUSION: A longer
      duration of symptom, multisegmental T2HSCs on sagittal MR images, and fuzzy focal
      T2HSCs on axial MR images were highly predictive of a poor surgical outcome for
      CSM. Smaller transverse area of the SC and bright T2HSCs were also associated
      with the prognosis of CSM.

PMID- 30241008
TI  - Enhancing contrast to noise ratio of hippocampi affected with mesial temporal
      sclerosis: A case-control study in children undergoing epilepsy surgeries.
AB  - OBJECTIVE: Detection of mesial temporal sclerosis (MTS) in children with epilepsy
      is important. We assessed whether an image-processing algorithm (Correlative
      Image Enhancement, CIE) could facilitate recognition of hippocampal signal
      abnormality in the presence of MTS by increasing contrast to noise ratio between
      affected hippocampus and normal gray matter. PATIENTS AND METHODS: Baseline
      coronal FLAIR images from brain MRIs of 27 children with epilepsy who underwent
      hippocampal resection were processed using CIE. These included 19 hippocampi with
      biopsy proven MTS and 8 biopsy proven normal hippocampi resected in conjunction
      with hemispherotomy. We assessed the effect of processing on contrast to noise
      ratio (CNR) between hippocampus and normal insular gray matter, and on assessment
      of hippocampal signal abnormality by two masked neuroradiologists. RESULTS:
      Processing resulted in a significant increase in mean CNR (from 3.9 +/- 5.3 to
      25.3 +/- 25.8; P < 0.01) for hippocampi with MTS, with a substantial (>100%)
      increase from baseline seen in 15/19 (78.9%) cases. Baseline CNR of 1.7 +/- 5.3
      for normal hippocampi did not change significantly after processing (1.8 +/- 5.3;
      P = 1.00). For one reader, baseline sensitivity (14/19; 73.6%) was unaffected but
      the specificity improved from 62.5% (5/8) to 100%. An increase in both
      sensitivity (from 73.6% to 78.9%) and specificity (from 62.5% to 75%) was seen
      for the second reader. CONCLUSION: By enhancing CNR for diseased hippocampi while
      leaving normal hippocampi relatively unaffected, CIE may improve the diagnostic
      accuracies of radiologists in detecting MTS-related signal alteration within the
      affected hippocampus.

PMID- 30241009
TI  - De Novo assembly and comparative transcriptome analyses of purple and green
      morphs of Apostichopus japonicus during body wall pigmentation process.
AB  - Pigmentation processes provide a traceable and relevant trait for understanding
      key issues in evolutionary biology such as adaptation, speciation and the
      maintenance of balanced polymorphisms. The sea cucumber Apostichopus japonicus,
      which has nutritive and medical properties, is considered the most valuable
      commercial species in many parts of Asia. Compared with the green morph, the
      purple morph is rare and has great appeal to consumers. However, little is
      currently known about the molecular mechanism of body color formation in A.
      japonicus, even in echinoderm. Here, we employ illumina sequencing to examine
      expression patterns of the gene network underlying body wall development in
      purple and green morphs of A. japonicus. Overall, the number of down-regulated
      genes in the green morph was significantly more than in the purple morph during
      the pigmentation stage. We observed dynamic expression patterns of a large number
      of pigment, regulation and growth genes from the "Melanogenesis", "Melanoma",
      "Wnt signaling pathway", "Notch signaling pathway", "epithelium development",
      "epidermal growth factor receptor binding","growth factor activity" and "growth",
      including contrasting expression patterns of these genes in green and purple
      morph. This study provides comprehensive lists of differentially expressed genes
      during body wall development in the green and purple morphs, revealing potential
      candidate genes that may be involved in regulating body color formation and
      polymorphism. These data will provide valuable information for future genetic
      studies on sea cucumbers elucidating the molecular mechanisms underlying
      pigmentation, and may support the culture of desirable color morphs.

PMID- 30241010
TI  - Pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives as new multi-targeted
      inhibitors of Aurora A/B and KDR.
AB  - Aurora A, Aurora B and Kinase Insert Domain-containing Receptor (KDR) play
      essential roles in sustained cancer growth. In the present study, eighteen
      pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine derivatives were designed and
      synthesized. Most of the prepared compounds exhibited obviously enzymatic (Aurora
      A/B and KDR) activities. Among these analogs, compound 17g displayed significant
      Aurora A/B and KDR potencies with IC50 values of 46.2 nM, 37.6 nM and 21.6 nM,
      respectively. The results of further biological assays showed that compound 17g
      possessed moderate anti-proliferative activities against SNU-5, MKN-45 and MKN-74
      cells lines, induced G2/M cell cycle arrest and apoptosis in MKN-45, MKN-74, SGC
      7901 and SNU-5 cell lines, provided acceptable pharmacokinetic profiles (F =
      63.8%), and inhibited the proliferation of SNU-5 tumors in vivo of mice. All of
      the above results suggested that pyrazolo[4,3-b]pyrimido[4,5-e][1,4]diazepine
      could be developed as a promising scaffold of multiple Aurora A/B and KDR
      inhibitors and 17g was worth of further research as a multi-targeted lead
      compound.

PMID- 30241011
TI  - Designing anticancer copper(II) complexes by optimizing 2-pyridine
      thiosemicarbazone ligands.
AB  - To develop potential next-generation metal anticancer agents, we designed and
      synthesised five Cu(II) 2-pyridine-thiosemicarbazone complexes by modifying the
      hydrogen atom at the N-4 position of ligands, and then investigated their
      structure-activity relationships and anticancer mechanisms. Modification of the N
      4 position with different groups caused significant differences in cellular
      uptake and produced superior antitumor activity. Cu complexes arrested the cell
      cycle at S phase, leading to down-regulation of levels of cyclin and cyclin
      dependent kinases and up-regulation of expression of cyclin-dependent kinase
      inhibitors. Cu complexes exerted chemotherapeutic effects via activating p53 and
      inducing production of reactive oxygen species to regulate expression of the B
      cell lymphoma-2 family of proteins, causing a change in the mitochondrial
      membrane potential and release of cytochrome c to form a dimer with apoptosis
      protease activating factor-1, resulting in activation of caspase-9/3 to induce
      apoptosis. In addition, Cu complexes inhibited telomerase by down-regulating the
      c-myc regulator gene and expression of the human telomerase reverse
      transcriptase.

PMID- 30241012
TI  - Branched pentapeptides as potent inhibitors of the vascular endothelial growth
      factor 165 binding to Neuropilin-1: Design, synthesis and biological activity.
AB  - The demonstrated involvement of VEGF165/NRP-1 complex in pathological
      angiogenesis has catalyzed interest in blocking this interaction to combat
      angiogenesis dependent diseases. It was shown before that Lys-Pro-Pro-Arg is a
      fairly strong inhibitor of the VEGF165/NRP-1 interaction. Our current findings
      suggest that the side chain elongation of the Lys1 by branching it with
      additional homoarginine (Har) residue, to obtain Lys(Har)-Pro-Pro-Arg, allows
      more effective inhibition. Moreover, increasing the flexibility of the middle
      part of molecule, in particular with simultaneous introduction of additional
      interacting elements at the second or third position, produced compounds up to 30
      fold more active (IC50 = 0.2 MUM) than the heptapeptide ATWLPPR (A7R) which is
      one of the first peptide known as an effective antagonist of the VEGF165 binding
      to NRP-1 and in vivo decreases breast cancer angiogenesis and growth. Herein, we
      present also the structure-activity study of Lys(Har)-Pro-Pro-Arg, discussing the
      design, synthesis, inhibitory activity, proteolytic stability and molecular
      modeling of the prepared derivatives. For two of the most active analogs the high
      proteolytic stability was also observed. These studies provide the next step for
      elucidating the optimal structure of the small peptidic inhibitors of VEGF165/NRP
      1 interaction that could serve as research tools or be prospective drug
      candidates.

PMID- 30241013
TI  - Kinetics of europium sorption to four different aluminum (hydr)oxides: Corundum,
      gamma-alumina, bayerite, and gibbsite.
AB  - Kinetic studies can improve our understanding of the environmental mobility of
      radionuclides by providing insight into sorption mechanisms occurring at the
      mineral-water interface. While nearly identical equilibrium europium sorption
      edges are obtained for gibbsite (gamma-Al(OH)3), bayerite (alpha-Al(OH)3),
      corundum (alpha-Al2O3), and gamma-Al2O3, differences in surface acidity and
      crystal structure result in distinct reaction rates. Batch kinetic experiments
      were performed to investigate europium sorption to four aluminum (hydr)oxide
      minerals as a function of time (10-120 min), mineral concentration (0.5-50 m2 L
      1), pH (5-7), and europium concentration (10-8-10-6 M). Linear and non-linear
      pseudo-first and pseudo-second order rate equations were used to fit the data.
      The overall reaction rates and reaction orders with respect to proton
      concentration, mineral concentration, and europium concentration were determined,
      leading to a governing rate law for each mineral system. Europium sorption is
      characterized by a two-step reaction with a fast initial sorption step followed
      by a slower sorption or aging process. The pseudo-second order equations resulted
      in better model fits of the data. Using the non-linear pseudo-second order rate
      constants, it was observed that the reaction orders for each mineral system were
      similar but resulted in different overall reaction rates following the trend
      bayerite ~ gamma-Al2O3 > corundum > gibbsite. However, the calculated reaction
      orders are similar to those previously reported for plutonium(IV/V) interactions
      with iron (oxyhydr)oxide minerals, suggesting that these binary systems share
      similar elementary reactions.

PMID- 30241014
TI  - Effects of cesium accumulation on chlorophyll content and fluorescence of
      Brassica juncea L.
AB  - The aim of our study was to investigate the toxicological mechanism of cesium on
      Indian mustard (Brassica juncea L.). The impact of cesium toxicity to plants was
      evaluated using phytophysiology and genetic methods. In this study, Brassica
      juncea was grown on Cs-contaminated Hoagland's nutrient solution, and chlorophyll
      content, chlorophyll fluorescence, and Cs bioaccumulation were measured.
      Transcriptome data was used to perform an in-depth analysis of the molecular
      mechanisms underlying the effects of Cs accumulation. The results showed that Cs
      accumulated up to 3586.70 mg kg-1 in B. juncea treated with 100 mg L-1 Cs. The
      chlorophyll content and several chlorophyll fluorescence parameters (Fv/F0,
      Fv/Fm, PhiPS II, qP, and NPQ) significantly decreased under Cs exposure. The
      starting process of PSII was also inhibited under higher Cs conditions. These
      results indicate that excessive Cs can damage PS II in leaves, decreasing
      photochemical activity and the energy conversion rate. Further analysis revealed
      that Cs interfered with the expression of chloroplastic metabolic genes (25 up
      and 36 down) and inhibited the expression of PsaB, psbC, PetF, LHCA1, and LHCB5.
      The results indicate that stable Cs leads to abnormal expression of genes related
      to photosynthesis pathway, blocking the electron transport process from
      plastoquinone-QA to plastoquinone-QB, resulting in abnormal photosynthesis, which
      leads to abnormal growth of B. juncea.

PMID- 30241015
TI  - Associations between depression, anxiety and medication adherence among patients
      with arterial hypertension: Comparison between persons exposed and non-exposed to
      radiation from the Semipalatinsk Nuclear Test Site.
AB  - In this study, we investigated the association between depression, anxiety and
      medication adherence in patients with arterial hypertension living in East
      Kazakhstan region. The sample size included 795 patients, of whom 403 patients
      were exposed to radiation at the Semipalatinsk Nuclear Test Site from 1949 to
      1989, while 395 patients were unexposed to radiation due to their very remote
      residence from the Site at the same period. Both exposed and unexposed patients
      showed no significant differences concerning body mass index, smoking habit, the
      presence of hypercholesterolemia, and hypertension grade. Patients with arterial
      hypertension previously exposed to radiation had significantly higher rates of
      low medication adherence, subclinical and clinical depression, situational
      anxiety of moderate and severe grade, and personal anxiety of moderate grade. A
      logistic regression analysis allowed us to identify the presence of significant
      positive association between medication adherence and anxiety in exposed patients
      (OR = 4041 (95%CI:1709-9556) p = 0.001) and marginal association (OR = 2998
      (95%CI:1008-8915) p = 0.048) between the same parameters in unexposed patients.
      It might prove to be useful to introduce psychological and medical counseling
      with an emphasis on strengthening of medication adherence and to inform the local
      population about radiation effects and dosimetry data.

PMID- 30241016
TI  - Human interleukin-34-derived macrophages have increased resistance to HIV-1
      infection.
AB  - The establishment of latent HIV-1 reservoirs in terminally differentiated cells
      represents a major impediment to the success of antiretroviral therapies.
      Notably, macrophages (Mphis) are susceptible to HIV-1 infection and recent
      evidence suggests that they may be involved in long-term HIV-1 persistence. While
      the extensive functional heterogeneity seen across the Mphi cell lineage
      parallels the spectrum of HIV-1 susceptibility reported across these cell
      subsets, the facets of Mphi HIV-1 resistance and susceptibility remain to be
      fully defined. Notably, the differentiation of most Mphi subsets depends on
      signaling through the macrophage colony-stimulating factor receptor (M-CSFR),
      which in addition to M-CSF, is now known to bind the unrelated interleukin-34 (IL
      34) cytokine. The biological need for two M-CSFR ligands awaits full elucidation.
      Here, we report that Mphis differentiated from human peripheral blood monocytes
      with IL-34 are substantially more resistant to HIV-1 infection than M-CSF-derived
      Mphis. Moreover, while both Mphi subsets express comparable surface protein
      levels of the HIV-1 receptor and co-receptor, CD4 and CCR5 respectively, the IL
      34-Mphis express significantly greater levels of pertinent restriction factor
      genes, potentially accounting for their greater resistance to HIV-1 infection
      than that observed in M-CSF-Mphis. Together, our findings underline previously
      unexplored differentiation pathways resulting in HIV-1-susceptible and resistant
      Mphi subsets and pave the way for further research that may overcome one of the
      last major hurdles in developing more successful antiretroviral therapy.

PMID- 30241017
TI  - Improved signal fidelity in 4-pulse DEER with Gaussian pulses.
AB  - The introduction of arbitrary waveform generator (AWG) technology and the
      availability of high power microwave amplifiers mark a "new era" in pulse EPR due
      to significant sensitivity improvements and the possibility to perform novel
      types of experiments. We present an optimized 4-pulse DEER setup that uses
      Gaussian observer pulses (GaussDEER) in connection with a Gaussian/shaped pump
      pulse. Gaussian pulses allow to experimentally remove the "2+1" pulse train ESE
      signal which is intrinsically present in any DEER experiment performed with
      rectangular pulses. Further signal improvements are obtained with shaped pump
      pulses, which can significantly increase the modulation depth of the DEER
      experiment due to their tailored excitation bandwidth. Although sequences like CP
      (Carr-Purcell) DEER offer advantages such as a prolongation of the dipolar
      evolution time, they suffer from post-processing of the time-domain data to
      remove artifacts. Therefore, it is worth having a 4-pulse DEER experiment free of
      residual "2+1" signal since this is still the main dipolar spectroscopic
      technique used in structural biology. In this work we focus on nitroxides, which
      are the spin probes primarily used in site-directed spin labeling studies of
      biomolecules, however, the advantages introduced by Gaussian pulses can be
      extended to any spin type.

PMID- 30241018
TI  - MR elastography at 1 Hz of gelatin phantoms using 3D or 4D acquisition.
AB  - Magnetic Resonance Elastography (MRE) detects induced periodic motions in
      biological tissues allowing maps of tissue mechanical properties to be derived.
      In-vivo MRE is commonly performed at frequencies of 30-100 Hz using external
      actuation, however, using cerebro-vascular pulsation at 1 Hz as a form of
      intrinsic actuation (IA-MRE) eliminates the need for external motion sources and
      simplifies data acquisition. In this study a hydraulic actuation system was
      developed to drive 1 Hz motions in gelatin as a tool for investigating the
      performance limits of IA-MRE image reconstruction under controlled conditions.
      Quantitative flow (QFLOW) MR techniques were used to phase encode 1 Hz motions as
      a function of gradient direction using 3D or 4D acquisition; 4D acquisition was
      twice as fast and yielded comparable motion field and concomitant image
      reconstruction results provided the motion signal was sufficiently strong. Per
      voxel motion noise floor corresponded to a displacement amplitude of about 20-30
      MUm. Signal to noise ratio (SNR) was 94 +/- 17 for 3D and dropped to 69 +/- 10
      for the faster 4D acquisition, but yielded octahedral shear stress and shear
      modulus maps of high quality that differed by only about 20% on average. QFLOW
      measurements in gel phantoms were improved significantly by adding Mn(II) to
      mimic relaxation rates found in brain. Overall, the hydraulic 1 Hz actuation
      system when coupled with 4D sequence acquisition produced a fast reliable
      approach for future IA-MRE phantom evaluation and contrast detail studies needed
      to benchmark imaging performance.

PMID- 30241019
TI  - Identifying windows of susceptibility for maternal exposure to ambient air
      pollution and preterm birth.
AB  - Maternal exposure to ambient air pollution has been associated with preterm birth
      (PTB), however, entire pregnancy or trimester-specific associations were
      generally reported, which may not sufficiently identify windows of
      susceptibility. Using birth registry data from Guangzhou, a megacity of southern
      China (population ~14.5 million), including 469,975 singleton live births between
      January 2015 and July 2017, we assessed the association between weekly air
      pollution exposure and PTB in a retrospective cohort study. Daily average
      concentrations of PM2.5, PM10, NO2, SO2, and O3 from 11 monitoring stations were
      used to estimate district-specific exposures for each participant based on their
      district residency during pregnancy. Distributed lag models (DLMs) incorporating
      Cox proportional hazard models were applied to estimate the association between
      weekly maternal exposure to air pollutant and PTB risk (as a time-to-event
      outcome), after controlling for temperature, seasonality, and individual-level
      covariates. We also considered moderate PTB (32-36 gestational weeks) and very
      PTB (28-31 gestational weeks) as outcomes of interest. Hazard ratios (HRs) and
      95% confidential intervals (95% CIs) were calculated for an interquartile range
      (IQR) increase in air pollutants during the study period. An IQR increase in
      PM2.5 exposure during the 20th to 28th gestational weeks (27.0 MUg/m3) was
      significantly associated with PTB risk, with the strongest effect in the 25th
      week (HR = 1.034, 95% CI:1.010-1.059). The significant exposure windows were the
      19th-28th weeks for PM10, the 18th-31st weeks for NO2, and the 23rd-31st weeks
      for O3, respectively. The strongest associations were observed in the 25th week
      for PM10 (IQR = 37.0 MUg/m3; HR = 1.048, 95% CI:1.034-1.062), the 26th week for
      NO2 (IQR = 29.0 MUg/m3; HR = 1.060, 95% CI:1.028-1.094), and in the 28th week for
      O3 (IQR = 90.0 MUg/m3; HR = 1.063, 95% CI:1.046-1.081). Similar patterns were
      observed for moderate PTB (32-36 gestational weeks) and very PTB (28-31
      gestational weeks) for PM2.5, PM10, NO2 exposure, but the effects were greater
      for very PTB. We did not observe any association between pregnancy SO2 exposure
      and the risk of PTB. Our results suggest that middle to late pregnancy is the
      most susceptible air pollution exposure window for air pollution and PTB among
      women in Guangzhou, China.

PMID- 30241020
TI  - Human health risk assessment of pharmaceuticals in treated wastewater reused for
      non-potable applications in Sharjah, United Arab Emirates.
AB  - Pharmaceuticals and personal care products are an integral part of societal
      health yet their presence in various environmental compartments, including
      treated wastewaters, has sparked concerns towards possible human and ecological
      health effects. The current study aims to characterize human health risks posed
      by ten pharmaceuticals quantified in wastewater treatment plant effluents where
      water is reused mainly for landscape irrigation. Receptors were identified as
      children playing in green areas, adult landscape workers, and adult users of
      athletic and golf courses irrigated by treated wastewater. The human health risk
      assessment model exhibited safe exposure (RQ < 1) to all pharmaceuticals for all
      receptors through both dermal and ingestion exposure pathways. RQs were highest
      for the landscape worker followed by children playing in green areas and then
      adult using the athletic fields. RQs were highest to lowest in the following
      order of pharmaceuticals: acetaminophen, metoprolol, ciprofloxacin, erythromycin,
      ofloxacin, sulfadiazine, sulfamethoxazole, sulfapyridine, risperidone, and
      sulfamethazine. Such risk assessment findings aid in supporting decisions to
      optimize wastewater treatment and reuse strategies, as well as safeguard public
      and environmental health.

PMID- 30241021
TI  - Childhood leukaemia risk and residential proximity to busy roads.
AB  - BACKGROUND: Current evidence suggests that childhood leukaemia can be associated
      with residential traffic exposure; nevertheless, more results are needed to
      support this conclusion. OBJECTIVES: To ascertain the possible effects of
      residential proximity to road traffic on childhood leukaemia, taking into account
      traffic density, road proximity and the type of leukaemia (acute lymphoid
      leukaemia or acute myeloid leukaemia). METHODS: We conducted a population-based
      case-control study of childhood leukaemia in Spain, covering the period 1990
      2011. It included 1061 incidence cases gathered from the Spanish National
      Childhood Cancer Registry and those Autonomous Regions with 100% coverage, and
      6447 controls, individually matched by year of birth, sex and autonomous region
      of residence. Distances were computed from the respective participant's
      residential locations to the different types of roads and four different buffers.
      Using logistic regression, odds ratios (ORs) and 95% confidence intervals
      (95%CIs), were calculated for four different categories of distance to roads.
      RESULTS: Cases of childhood leukaemia had more than three-fold increased odds of
      living at <50 m of the busiest motorways compared to controls (OR = 2.90; 95%CI =
      1.30-6.49). The estimates for acute lymphoid leukaemia (ALL) were slightly higher
      (OR = 2.95; 95%CI = 1.22-7.14), while estimates for cases with the same address
      at birth and at diagnosis were lower (OR = 2.40; 95%CI = 0.70-8.30). CONCLUSIONS:
      Our study agrees with the literature and furnishes some evidence that living near
      a busy motorway could be a risk factor for childhood leukaemia.

PMID- 30241022
TI  - Comparative study of a simulated incident with multiple victims and immersive
      virtual reality.
AB  - OBJECTIVES: The main objective of the study is to determine the efficiency in the
      execution of the START (Simple Triage and Rapid Treatment) triage, comparing
      Virtual Reality (VR) to Clinical Simulation (CS) in a Mass Casualty Incident
      (MCI). The secondary objective is to determine the stress produced in the health
      professionals in the two situations described. MATERIALS: A comparative study on
      the efficiency and the stress during triage in a MSI was conducted. The basal and
      post levels of salivary alpha-amylase (sAA) activity were measured in all the
      participants before and after the simulation. RESULTS: The percentage of victims
      that were triaged correctly was 87.65% (SD = 8.3); 88.3% (SD = 9.65) for the
      Clinical Simulation with Actors (CSA) group and 87.2% (SD = 7.2) for the Virtual
      Reality Simulation (VRG) group, without any significant differences (p = 0.612)
      between both groups. The basal sAA was 103.26 (SD = 79.13) U/L with a significant
      increase (p < 0.001) with respect to the post-simulation levels (182.22, SD =
      148.65 U/L). The increase of sAA was 80.70 (SD = 109.67) U/mL, being greater for
      the CSA group than the VRG group. CONCLUSION: The results show that virtual
      reality method is as efficient as clinical simulation for training on the
      execution of basic triage (START model). Also, based on the sAA results, we can
      attest that clinical simulation creates a more stressful training experience for
      the student, so that is should not be substituted by the use of virtual reality,
      although the latter could be used as a complementary activity.

PMID- 30241023
TI  - Pomegranate chitinase III: Identification of a new allergen and analysis of
      sensitization patterns to chitinases.
AB  - Allergy to pomegranate is often associated with severe symptoms. Two allergens
      have previously been described: 9k-LTP Pun g 1 and pommaclein Pun g 7. This study
      describes the isolation of a chitinase III, identified by direct protein
      sequencing and mass spectrometry. It is a 29-kDa protein showing 69% sequence
      identity with the latex hevamine and IgE binding in dot blotting, immunoblotting
      and FABER(r)test. Chitinase-specific IgE were detected in 69 of 357 patients
      sensitized to one or more pomegranate allergenic preparations present on the
      FABER(r)test. Using this test, 19.2% of the patients sensitized to kiwifruit
      chitinase IV were also sensitized to pomegranate chitinase III, rather than to
      latex chitinase I (7.2%) with which it shares the N-terminal hevein-like domain.
      In conclusion, a new allergen has been identified, contributing to improving food
      allergy diagnosis. This study reveals the important role of chitinases III and IV
      as allergy sensitizers and prompts further investigations.

PMID- 30241024
TI  - Clinical features of differential diagnosis between unipolar and bipolar
      depression in a drug-free sample of young adults.
AB  - INTRODUCTION: Subjects with bipolar disorder suffering of a depressive episode
      are frequently misdiagnosed as unipolar depression, being important studies
      assessing the differential diagnosis between bipolar and unipolar depression.
      OBJECTIVE: To assess the sociodemographic and clinical features of drug-free
      young adults in a depressive episode of bipolar or unipolar disorder in order to
      identify factors that may differentiate these psychiatric conditions. METHODS:
      This is a cross-sectional study with 241 young adults aged between 18 and 29
      years who were evaluated using the Structured Clinical Interview for DSM-IV
      (SCID). The sample comprised patients with BD (n = 89) and major depressive
      disorder (n = 152), experiencing a depressive episode and not using psychoactive
      drugs or illicit psychoactive substances. RESULTS: The characteristics associated
      with bipolar depression were being male (p < 0.001), with a family history of BD
      (p = 0.013), a higher frequency of childhood traumatic experiences (p = 0.001),
      younger age of onset of mood disorder (p = 0.004), many previous depressive
      episodes (p = 0.027), greater severity of depressive symptoms (p < 0.001) and
      day/night reversal (p = 0.013). Those with unipolar depression showed a higher
      frequency of biological rhythm disturbances (p < 0.001), and diurnal preference
      (p = 0.028). LIMITATIONS: The sample has not included subjects with severe
      suicide risk, a possible important marker in differentiate unipolar from bipolar
      depression. CONCLUSION: Some clinical aspects may contribute to an early
      differential diagnosis of both bipolar and unipolar depression even in the
      initial stages of the disease.

PMID- 30241025
TI  - Self-disgust as a potential mechanism explaining the association between
      loneliness and depression.
AB  - BACKGROUND: Loneliness and self-disgust have been considered as independent
      predictors of depressive symptoms. In the present study, we hypothesized that
      self-disgust can explain the association between loneliness and depression, and
      that emotion regulation strategies interact with self-disgust in predicting
      depressive symptoms. METHODS: Three hundred and seventeen participants (M = 29.29
      years, SD = 14.11; 76.9% females) completed structured anonymous self-reported
      measures of loneliness, self-disgust, emotion regulation strategies, and
      depressive symptoms. RESULTS: One-way MANOVA showed that participants in the high
      loneliness group reported significantly higher behavioural and physical self
      disgust, compared to those in the middle and low-loneliness groups. Bootstrapped
      hierarchical linear regression analysis showed that self-disgust significantly
      improved predicted variance in depressive symptoms, after controlling for the
      effects of loneliness. Regression-based mediation modelling showed that both
      physical and behavioural self-disgust significantly mediated the association
      between loneliness and depression. Finally, moderated regression analysis showed
      that expressive suppression interacted with self-disgust in predicting depressive
      symptoms. LIMITATIONS: A cross-sectional design was used, and our study focused
      on expressive suppression and cognitive reappraisal but not on other aspects of
      emotion regulation or the modulation of emotional arousal and responses.
      CONCLUSIONS: We demonstrated, for the first time, that self-disgust plays an
      important role in the association between loneliness and depressive symptoms.
      Furthermore, variations in emotion regulation strategies can explain the
      association between self-disgust and depressive symptoms.

PMID- 30241026
TI  - Treatment effectiveness and tolerability outcomes that are most important to
      individuals with bipolar and unipolar depression.
AB  - OBJECTIVE: To evaluate patient-reported determinants of treatment effectiveness
      and tolerability amongst persons with major depressive or bipolar disorders.
      METHODS: The Depression and Bipolar Support Alliance (DBSA) conducted an online
      survey February 2016-April 2016 asking participants about which outcomes are most
      important in determining subjective treatment effectiveness and tolerability.
      RESULTS: In total, 896 participants completed the survey [49.9% unipolar
      depression (n = 447) and 50.1% bipolar depression (n = 449)]. Survey respondents
      reported several previous medication trials with the minority (25% of depression
      and 29% of bipolar group) of respondents reporting that their current treatment
      plan was completely effective. When asked how they know that the treatment is
      working, for both groups, the highest rated response was, "I don't feel overly
      anxious, agitated or irritable." Weight gain was the adverse effect that most
      commonly led respondents to discontinue a medication. Lethargy, emotional
      blunting, shaking/trembling and anxiety were also identified as common treatment
      emergent experiences leading to medication discontinuation in greater than one
      third of respondents. The bipolar group more frequently identified several signs
      that suggested treatment was working (e.g., improved neurocognitive function,
      improved sleep), as well as more frequently reported several reasons to
      discontinue medications (e.g., weight gain, trembling). CONCLUSION: Numerous
      factors emerged as important to patients when evaluating treatment effectiveness
      and tolerability. Some of these factors are inadequately assessed by current
      standard clinical trial outcome measures. Considering these important patient
      centred outcomes in future clinical trials, treatment guidelines and direct
      patient care may serve to improve patient satisfaction, quality of life and the
      therapeutic alliance.

PMID- 30241027
TI  - Suicide and other sudden death bereavement of immediate family members: An
      analysis of grief reactions six-months after death.
AB  - INTRODUCTION: While suicide bereavement has been assumed to be different from
      bereavement following death by other modes, a number of studies have reported
      that there are several similarities, particularly for violent deaths. The aims of
      the current study are to test, using confirmatory factor analysis, the factor
      structure of Grief Experience Questionnaire (GEQ) that has been proposed in other
      studies; and to compare short term grief reactions, mental health, and
      suicidality six-months after bereavement in close family members bereaved by
      suicide versus sudden death. METHODS: Participants were 142 adults who were
      bereaved following a suicide and 63 who were bereaved following the sudden death
      of a family member. Data were collected six-months after the death. RESULTS:
      Analyses did not show good fits for the factor structures proposed for the GEQ in
      earlier studies. However, a relatively good fit was found for an 8-factor version
      of the originally proposed GEQ. Bereavement type (suicide vs. sudden death)
      significantly predicted rejection, somatic reactions, stigmatisation,
      responsibility and shame on the GEQ, after adjusting for kinship type, gender,
      age, pre-bereavement diagnosis of mental illness and self-harm behaviours of both
      the deceased and the bereaved, and current mental health and suicidal ideation of
      the bereaved. LIMITATIONS: Different recruitment methods were used and response
      rates were relatively low. CONCLUSIONS: The new knowledge of bereaved experiences
      specific to suicide loss at six-months post death, should be channelled into
      determining the most practical and satisfactory ways to alleviate the impacts of
      these potentially changeable states of experience.

PMID- 30241028
TI  - Dance exposure, wellbeing and injury in collegiate Irish and contemporary
      dancers: A prospective study.
AB  - OBJECTIVES: Dance exposure and determinants of wellness in Irish dance (ID) and
      contemporary dance (CD) are under-investigated in pre-professional, collegiate
      cohorts. This study prospectively investigated these variables in ID and CD
      participants for one year. DESIGN: Prospective study. SETTING: University-level
      institutes of dance, United Kingdom (UK) and Ireland. PARTICIPANTS: Fifty (ID =
      21, CD = 29) full time students of dance at Trinity Laban Conservatoire of Music
      and Dance, (UK) and the University of Limerick, Ireland. MAIN OUTCOME MEASURES:
      Weekly hours of dance, general health, sleep quality, injury defined as "any pain
      or injury that impacted upon their ability to dance". RESULTS: Dance exposure
      varied considerably for both genres across the year. CD participants danced for
      more hours weekly (p < 0.001). Overall injury incidence (time-loss and non-time
      loss) was 10.6 and 8.4 injuries per 1000 h dancing for ID and CD groups
      respectively. 70.4% of injuries were non-time-loss. Better sleep (p = 0.007) and
      general health (p < 0.001) scores were negatively correlated with days
      lost/impacted by injury. CD participants reported a significantly higher dance
      exposure in the week prior to a time-loss injury than during the previous four
      weeks (p = 0.044). CONCLUSIONS: Dance exposure is erratic in these cohorts with
      dancers frequently performing when injured. Poor sleep, general health, and
      increased dance exposure may be associated with injury.

PMID- 30241029
TI  - Authentic practice environments to support undergraduate nursing students'
      readiness for hospital placements. A new model of practice in an on campus
      simulated hospital and health service.
AB  - This paper reports on a unique practice based learning model to prepare
      undergraduate nursing students for clinical placement. The learning and teaching
      model described in this paper outlines the establishment of an entire on-campus
      simulated hospital and health service (SHHS) at the University of South
      Australia, School of Nursing and Midwifery. The model is pedagogically structured
      to immerse students in an authentic clinical environment to achieve deep learning
      in preparation for safe practice. A quality improvement cycle was used to
      evaluate the outcomes of the model in two phases: Phase 1: Purposive sampling of
      first and second year Bachelor of Nursing students from 2012 to 2015 who were
      surveyed about their satisfaction with the model of learning. Bachelor of Nursing
      students were invited to complete a survey about their experience with the
      teaching and learning model employed in the SHHS in response to the question,
      'What aspects of the SHHS are the most important to your success?' Phase 2:
      External clinical stakeholders working with nursing students in clinical
      placements were asked to respond to questions about the preparedness of students
      educated in this model to transition to employment. The evaluation showed that
      the SHHS model positively influenced students' satisfaction and confidence and
      increased the perception of clinicians of the work readiness of students.

PMID- 30241030
TI  - Combination antitumor immunotherapy with VEGF and PIGF siRNA via systemic
      delivery of multi-functionalized nanoparticles to tumor-associated macrophages
      and breast cancer cells.
AB  - Given that vascular endothelial growth factor (VEGF) and placental growth factor
      (PIGF), over-expressed in breast cancer cells and M2-like tumor-associated
      macrophages (M2-TAMs) within tumor microenvironment (TME), work synergistically
      and independently in mediating tumor progression and immunosuppression,
      combinatorial immune-based approaches targeting them are expected to be a potent
      therapeutic modality for patients. Here, polyethylene glycol (PEG) and mannose
      doubly modified trimethyl chitosan (PEG = MT) along with citraconic anhydride
      grafted poly (allylamine hydrochloride) (PC)-based nanoparticles (NPs) (PEG =
      MT/PC NPs) with dual pH-responsiveness were developed to deliver VEGF siRNA
      (siVEGF)/PIGF siRNA (siPIGF) to both M2-TAMs and breast cancer cells for
      antitumor immunotherapy. With prolonged blood circulation and intelligent pH
      sensitivity, PEG = MT/PC NPs were highly accumulated in tumor tissues and then
      internalized in M2-TAMs and breast cancer cells via mannose-mediated active
      targeting and passive targeting, respectively. With the charge-reversal of PC,
      PEG = MT/PC NPs presented effective endosomal/lysosomal escape and intracellular
      siRNA release, resulting in efficient gene silencing. Due to the synergism
      between siVEGF and siPIGF in anti-proliferation of tumor cells and reversal of
      the TME from pro-oncogenic to anti-tumoral, PEG = MT/PC/siVEGF/siPIGF NPs (PEG =
      MT/PC/siV-P NPs) exerted robust suppression of breast tumor growth and lung
      metastasis. This combination strategy may provide a promising alternative for
      breast cancer therapy.

PMID- 30241033
TI  - Laryngeal sarcomas: A case series of 5 cases.
AB  - Primary sarcomas of the larynx are rare and miscellaneous. The most common is
      chondrosarcoma. Other sarcomas are very rare. Sarcomas can have heterogeneous
      morphologic features of spindle, small round, epithelioid, pleomorphic and giant
      cells. Laryngeal sarcomas may mimic carcinomas, lymphomas, small cell carcinoma,
      mesothelioma and melanoma. This imposes diagnostic challenges for unfamiliar
      pathologists particularly in small laryngeal biopsies. Our aim was to study the
      different types of sarcomas that can involve the larynx in our institution, to
      investigate their diagnostic challenges and potential pitfalls and to find
      helpful histologic clues to avoid misinterpretation and missed diagnosis. We
      performed a retrospective review study over 13 years. We retrieved 5 cases of
      laryngeal sarcomas. They included Kaposi sarcoma, low-grade chondrosarcoma,
      epithelioid angiosarcoma, polypoid leiomyosarcoma and small cell osteosarcoma.
      The age range was between 32 and 74 years with an average age of 52 years. The
      male to female ratio was 3:2. The Kaposi sarcoma and chondrosarcoma were
      correctly diagnosed. The angiosarcoma was initially missed as recurrent
      carcinoma. The leiomyosarcoma was initially inferred as polypoid sarcomatoid
      squamous cell carcinoma. The small cell osteosarcoma initiated the differential
      diagnosis of high-grade lymphoma, small cell carcinoma, undifferentiated
      carcinoma, Ewing sarcoma and rhabdomyosarcoma. An implementation of a panel of
      immunohistochemical markers guided by certain histomorphologic clues was helpful
      to make the correct diagnosis. Pathologists should be aware of the morphologic
      spectrum and different growth patterns of laryngeal sarcomas.
      Immunohistochemistry studies are essential. Correct diagnosis, classification and
      grading of laryngeal sarcomas are clinically important for the prognosis and
      appropriate management of patients.

PMID- 30241031
TI  - Identification of a functional antioxidant response element at the HIF1A locus.
AB  - Reactive oxygen species (ROS), which are a byproduct of oxidative metabolism,
      serve as signaling molecules in a number of physiological settings. However, if
      their levels are not tightly maintained, excess ROS lead to potentially cytotoxic
      oxidative stress. Accordingly, several transcriptional regulatory networks have
      evolved to include components that are highly ROS-responsive. Depending on the
      context, these regulatory networks can leverage ROS to respond to nutrient
      conditions, metabolism, or other physiological signals, or to respond to
      oxidative stress. However, ROS signaling is complex, so regulatory interactions
      between various ROS-responsive transcription factors are still being mapped out.
      Here we show that the transcription factor NRF2, a key regulator of the adaptive
      response to oxidative stress, directly regulates expression of HIF1A, which
      encodes HIF1alpha, a key transcriptional regulator of the adaptive response to
      hypoxia. We used an integrative genomics approach to identify HIF1A as a ROS
      responsive transcript and we found an NRF2-bound antioxidant response element
      (ARE) approximately 30 kilobases upstream of HIF1A. This ARE sequence is deeply
      conserved, and we verified that it is directly bound and activated by NRF2. In
      addition, we found that HIF1A is upregulated in breast and bladder tumors with
      high NRF2 activity. Taken together, our results demonstrate that NRF2 targets a
      functional ARE at the HIF1A locus, and reveal a direct regulatory connection
      between two important oxygen responsive transcription factors.

PMID- 30241034
TI  - Clinical presentation of ductal carcinoma in situ of breast with intraluminal
      crystalloids: Radiologic-histologic correlation.
AB  - Intraluminal crystalloids have rarely been described in the breast, particularly
      in cases with ductal carcinoma in situ (DCIS). We recently encountered a case of
      DCIS of the breast associated with numerous intraluminal crystalloids. The
      patient presented with a mass in the right breast, and microcalcifications were
      detected on screening and diagnostic mammograms; the patient underwent needle
      biopsies, lumpectomy, and skin-sparing mastectomy. Invasive ductal carcinoma
      associated with extensive DCIS was diagnosed. Multiple refractile, eosinophilic
      crystalloids, with variable morphologies including rectangular, triangular and
      needle-like with sharp borders, were observed within the lumina of DCIS, besides
      calcium phosphate microcalcifications. We report this case together with a
      literature review on crystalloid-containing lesions in breast and non-breast
      tissues. We also studied radiologic findings of these crystalloids using a
      specimen radiograph.

PMID- 30241035
TI  - Granular cell tumor in a premenstrual female breast.
AB  - Granular cell tumor is an exceedingly rare pediatric breast mass, derived from
      Schwann cells which are most commonly observed in the oral cavity, skin, and
      subcutaneous tissue. When they occur in the breast, they can mimic intrinsic
      breast masses. Most cases are benign, but malignant cases have been reported. We
      present a case of a premenstrual, African-American 9 year old female with a
      painful right breast mass originally felt to be an epidermal inclusion cyst. An
      ultrasound was performed 17 months after original presentation which demonstrated
      a 1 cm well-circumscribed solid ovoid mass. Despite the relatively small size and
      benign imaging appearance of the mass, surgical resection was performed for
      symptom relief given the associated pain. This is the first known case of
      granular cell tumor of the breast in a premenstrual female.

PMID- 30241036
TI  - Reply to correspondence "Cauda equina involvement following dengue fever".

PMID- 30241032
TI  - Myostatin knockout induces apoptosis in human cervical cancer cells via elevated
      reactive oxygen species generation.
AB  - Myostatin (Mstn) is postulated to be a key determinant of muscle loss and
      cachexia in cancer. However, no experimental evidence supports a role for Mstn in
      cancer, particularly in regulating the survival and growth of cancer cells. In
      this study, we showed that the expression of Mstn was significantly increased in
      different tumor tissues and human cancer cells. Mstn knockdown inhibited the
      proliferation of cancer cells. A knockout (KO) of Mstn created by clustered
      regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated
      protein (Cas) 9 (CRISPR/Cas9) induced mitochondria-dependent apoptosis in HeLa
      cells. Furthermore, KO of Mstn reduced the lipid content. Molecular analyses
      demonstrated that the expression levels of fatty acid oxidation-related genes
      were upregulated and then increased rate of fatty acid oxidation. Mstn deficiency
      induced apoptosis took place along with generation of reactive oxygen species
      (ROS) and elevated fatty acid oxidation, which may play a role in triggering
      mitochondrial membrane depolarization, the release of cytochrome c (Cyt-c), and
      caspase activation. Importantly, apoptosis induced by Mstn KO was partially
      rescued by antioxidants and etomoxir, thereby suggesting that the increased level
      of ROS was functionally involved in mediating apoptosis. Overall, our findings
      demonstrate a novel function of Mstn in regulating mitochondrial metabolism and
      apoptosis within cancer cells. Hence, inhibiting the production and function of
      Mstn may be an effective therapeutic intervention during cancer progression and
      muscle loss in cachexia.

PMID- 30241037
TI  - Recurrent disseminated encephalomyelitis: A case report and literature review.
AB  - BACKGROUND: Acute disseminated encephalomyelitis has been understood as a
      monophasic, often post-infectious illness that predominantly affects the
      pediatric population. Though that describes the majority of cases, exceptions do
      exist. In this case report, we present an adult case of recurrent disseminated
      encephalomyelitis (DEM) and review the available literature on this clinical
      entity. METHODS: PubMed search performed using the terms "MDEM" and "Recurrent
      ADEM" in April 2018. A total of 23 items resulted for the first search and
      another 142 for the second. We selected articles that described cases of
      recurrent ADEM with a preference for those publications describing adult cases
      and those written in English language. CONCLUSION: Recurrent disseminated
      encephalomyelitis is a distinct clinical entity that has features which overlap
      with multiple sclerosis, making it imperative to distinguish the two. Our case
      presentation and accompanying literature review highlights the limited scope of
      data available on recurrent DEM and the need for further study.

PMID- 30241038
TI  - Examination of gas and solid products during the preparation of activated carbon
      using phosphoric acid.
AB  - Activating agents play significant roles in the preparation of activated carbon
      (AC) from biomasses and their wastes, which are widely used in AC production.
      Application methods are also important for the production process. Products give
      remarkable ideas regarding the method and heat treatment process. The activated
      carbon was produced from waste tea in accordance with either the conventional
      method or microwave energy pretreated method using phosphoric acid (H3PO4) as
      activating agent. The yields of the activated carbons were 51.8% for conventional
      method and 46.0% for microwave pretreated method. The acid suppressed the
      formation of tar and promoted the amount of solid and aromatic structure
      accordance to sp2 hybridisation. Additionally, the waste tea was directly
      carbonised (without H3PO4) and the yield was 36.3%. Major gas (H2, CH4, C2H6,
      C2H4, CO2 and CO) products obtained during heat treatment process in a
      conventional furnace were examined in terms of quantity and quality. The solid
      products were characterised in terms of surface area, pore size and surface
      properties. The result of gas analysis showed that phosphoric acid affected
      formation of activated carbon mechanism and significant reactions occurred during
      microwave pretreatment process.

PMID- 30241040
TI  - Potential influence of climate and anthropogenic variables on water security
      using blue and green water scarcity, Falkenmark index, and freshwater provision
      indicator.
AB  - Land use change and climate variability have significantly altered the regional
      water cycle over the last century thereby affecting water security at a local to
      regional scale. Therefore, it is important to investigate how the climate, land
      use change, and water demand potentially influence the water security by applying
      the concept of water footprint. An integrated hydrological modeling framework
      using SWAT (Soil and Water Assessment Tool) model was developed by considering
      both anthropogenic (e.g. land use change, water demand) and climatic factors to
      quantify the spatio-temporal variability of water security indicators such as
      blue water scarcity, green water scarcity, Falkenmark index, and freshwater
      provision indicators in Savannah River Basin (SRB). The SRB witnesses a
      significant change in land use land cover (e.g. forest cover, urban area) as well
      as water demand (e.g. irrigation, livestock production). Overall our results
      reveal that, SRB witnessed a significant decrease in blue water due to the
      climate variability indicating that the precipitation has more control over the
      blue water resources. Whereas, green water was more sensitive to changes in land
      use pattern. In addition, the magnitude of various water security indicators are
      different within each county suggesting that water scarcity are controlled by
      various factors within a region. An integrated assessment of water footprint,
      environmental flow, anthropogenic factors, and climatic variables can provide
      useful information on the rising (how and where) of water related risk to human
      and ecological health.

PMID- 30241039
TI  - Numerical simulation and exploration of electrocoagulation process for arsenic
      and antimony removal: Electric field, flow field, and mass transfer studies.
AB  - In order to intuitively and clearly evaluate the potential and current
      distribution, the fluid flow and mixing, as well as mass transfer involved in
      electrocoagulation process for As and Sb removal, numerical simulation of
      electric field, flow field and mass transfer were constructed by Comsol
      Multiphysics and verified by experiments. Results displayed that the primary
      current and potential distribution were improved by changing electrode distance
      or adding insulator in a batch reactor. When configuration 2 and 2 cm electrode
      distance were applied, a more uniform primary current distribution and higher
      electrode current efficiency were obtained. In a continuous flow reactor, the
      increase of flow rate resulted in the left shift of the peak in residence time
      distribution curve, gradual decrease of the tailing area, reduction of the
      stagnation zone, and more uniform mixing of the fluid. However, higher than 0.043
      L/min was unfavorable to the formation of flocs and its effective combination
      with pollutants. According to the simulation of mass transfer, at the initial
      stage, the rate of electrolysis/hydrolysis was greater than that of mass
      transfer. Fe2+, OH-, and Fe(OH)2 were primarily concentrated on the anode,
      cathode, and between the two electrodes, respectively. Under the action of
      electromigration, diffusion and convection, the concentration distribution of
      Fe(OH)2 increased at the direction of streamline. The concentration of Fe2+ and
      OH- achieved the minimum value at the outlet. However, Fe(OH)+ concentration and
      distribution were hardly affected by the treatment time, and once generated,
      immediately proceed to the next hydrolysis reaction.

PMID- 30241041
TI  - Spatiotemporal changes in soil phosphorus characteristics in a submerged aquatic
      vegetation-dominated treatment wetland.
AB  - In South Florida, stormwater treatment areas (STAs) are used to reduce phosphorus
      (P) in runoff from agricultural areas before water is discharged into the
      Everglades Protection Area. The Everglades STAs retain a significant amount of P
      and play an important role in Everglades restoration. Wetland soils generally are
      long-term sinks for P; therefore, the sustainability of STA treatment performance
      can be assessed by tracking changes in soil characteristics. This study evaluated
      the spatiotemporal changes in soil P and related physicochemical characteristics
      in the unconsolidated floc and underlying surface soil layer (0-10 cm) of a 920
      ha submerged aquatic vegetation (SAV)-dominated wetland (STA-2 Cell 3).
      Physicochemical properties in soil cores collected in 2003, 2007, 2009, and 2015
      were evaluated and compared using geostatistical methods. Results indicated a
      gradual increase in floc depth over time. Total P (TP) concentrations in the floc
      were significantly higher than in the surface soil. Slight but statistically
      nonsignificant increases of mean TP in floc were observed. There was a
      significant increase in P storage in the floc layer between 2003 and 2007, with
      more P stored in the surface soil layer. Interpolated maps showed consistently
      higher TP and P storage values in the floc and surface soil near inflow areas of
      the cell during all sampling events. Furthermore, the 2003 to 2015 change maps
      showed TP and P storage decreasing from inflow to outflow. Bulk density (BD) in
      floc was approximately half of surface soil BD. Significant decline in the
      percentage of ash-free dry weight (AFDW) in floc from 2003 to 2007 indicated an
      increase in mineral content. This is consistent with increases in total calcium
      (TCa) in the floc, which was up to four times higher than in the surface soil
      layer. This indicates that TCa plays a central role in defining the
      characteristics of SAV cells. Overall, despite the heterogeneity of sediment
      attributes in the system, temporal trends and spatial patterns were observed in
      the physicochemical characteristics of soils. These trends and patterns can be
      used to understand long-term changes in large-scale treatment wetlands. Such
      insights are useful for optimizing and sustaining the treatment performance of
      STAs.

PMID- 30241042
TI  - Immune-based therapeutic approaches to virus-associated cancers.
AB  - It is estimated that 60-70% of cancers associated with infectious agents are
      linked to viral infections. Both RNA and DNA viruses that can establish
      persistent infection exploit various mechanisms including host cell
      immortalization through genomic instability, chronic inflammation and immune
      escape, to promote oncogenic transformation of human cells. Expression of
      selected viral proteins in malignant cells provides a unique opportunity to
      employ targeted therapies that can disrupt the cellular proliferation and prevent
      collateral damage caused by standard clinical therapies. While vaccination can be
      used to prevent infection before malignant transformation, immune-based therapies
      based on adoptive transfer of T cells and/or antibodies have emerged as powerful
      tools for the treatment of virus-associated cancers. Here we discuss recent
      advances and future prospects of immune-based therapies for virus-associated
      cancers.

PMID- 30241043
TI  - Strategies for immune evasion by human tumor viruses.
AB  - Immune evasion is a hallmark of viral persistence. For the seven human tumor
      viruses to establish lifelong infection in their hosts, they must successfully
      control the host response to them. Viral inhibition of immune responses occurs at
      many levels. While some viruses directly target the pattern recognition receptors
      (PRR) of the innate immune system, they may also antagonize downstream effectors
      of PRR signaling cascades or activation of transcription, which would otherwise
      induce a type I interferon (IFN) and/or pro-inflammatory cytokine response.
      Secretion of IFN activates the type I interferon receptor (IFNAR) signaling
      pathway, which is also prone to viral inhibition. To evade the adaptive host
      response, viruses also target various mechanisms including antigen processing and
      presentation.

PMID- 30241044
TI  - A comprehensive laboratory assessment of the effects of sewer-dosed iron salts on
      wastewater treatment processes.
AB  - The effect of iron-dosing in the sewer system, on wastewater treatment processes,
      was investigated using laboratory-scale wastewater systems comprising sewers,
      wastewater treatment reactors, sludge thickeners, and anaerobic sludge digesters.
      Two systems, fed with real domestic wastewater, were operated for over a year.
      The experimental system received ferric chloride (FeCl3) dosing at 10 mgFe L-1 in
      the sewer reactor whereas the control system received none. Wastewater, sludge
      and biogas were extensively sampled, and analysed for relevant parameters. The
      FeCl3-dosed experimental system displayed a decreased sulfide concentration (by
      4.3 +/- 0.5 mgS L-1) in sewer effluent, decreased phosphate concentration (by 4.7
      +/- 0.5 mgP L-1) in biological treatment reactor effluent, and decreased hydrogen
      sulfide concentration in biogas (911.5 +/- 189.9 ppm to 130.0 +/- 5.9 ppm), as
      compared with the control system. The biological nitrogen removal performance of
      the treatment reactor, and biogas production in the anaerobic digester were not
      affected by FeCl3-dosing. Furthermore, the dewaterability of the anaerobically
      digested sludge was enhanced by 17.7 +/- 1.0%. These findings demonstrate that
      iron-dosing to sewers can achieve multiple benefits including sulfide removal in
      sewers, phosphorus removal during wastewater treatment, and hydrogen sulfide
      (H2S) removal during biogas generation. Therefore, an integrated approach should
      be taken when considering iron salts usage in an urban wastewater system.

PMID- 30241045
TI  - Contaminants of Emerging Concern as novel groundwater tracers for delineating
      wastewater impacts in urban and peri-urban areas.
AB  - Management and treatment of environmental impacts from wastewater treatment
      plants (WWTPs) is a major, worldwide, sustainability challenge. One issue
      associated with WWTP operation is the potential for groundwater contamination via
      leaking or infiltration of wastewater, particularly with inorganic nutrients
      (ammonia and nitrate) as well as persistent organic compounds. Despite the
      potential for such contamination to create environmental and health risks,
      conventional methods, such as the assessment of major ions, nutrients,
      bacteriological indicators and conventional tracers (such as stable and
      radiogenic isotopes) are often unable to provide accurate delineation of multiple
      potential sources of contamination. This is particularly important for WWTPs
      which often occur in urban, peri-urban or intensively farmed agricultural areas
      where multiple potential sources (such as livestock, fertilisers, wastewater
      irrigation, and domestic septic systems) may contribute similar contaminants.
      This review explores the applicability of promising novel groundwater tracers,
      such as Contaminants of Emerging Concern (CECs) and isotopic tracers, which can
      be used in conjunction with conventional tracers (i.e. 'co-tracers') to provide a
      more definitive assessment of contaminant sources, plume delineation and even
      (potentially) indicating the age of contamination (e.g., recent vs. legacy). The
      suitability of the novel groundwater tracers is evaluated according to four key
      criteria: (i). sufficient presence in raw wastewater and/or treated effluents;
      (ii) diagnostic of WWTP impacts as opposed to other potential off-site
      contamination sources; (iii) persistence in the subsurface environment; and (iv)
      amenable to rapid and sensitive analysis. Further analysis of various classes of
      CECs along with improved detection limits associated with improvements in
      analytical methodologies should allow for future application of promising
      groundwater tracers, providing WWTP operators and regulatory authorities a more
      definitive toolbox with which to assess groundwater contamination associated with
      site operations. These include: persistent pharmaceuticals and personal care
      products (carbamazepine, crotamiton, primidone, atenolol and sulfamethoxazole),
      artificial sweeteners (acesulfame, sucralose, saccharin and cyclamate) and
      potentially, certain pesticides (atrazine and simazine).

PMID- 30241046
TI  - PIG11 over-expression predicts good prognosis and induces HepG2 cell apoptosis
      via reactive oxygen species-dependent mitochondrial pathway.
AB  - P53-induced protein 11 (PIG11), one of the primeval transcriptional targets of
      p53, is up-regulated in apoptosis induced by multiple chemopreventive agents and
      is involved in tumorigenesis or tumor development. Nevertheless, the clinical
      value and biological role of PIG11 in hepatocellular carcinoma (HCC) are still
      unknown. In the present article, we explored the expression pattern of PIG11 in
      HCC tumor tissues, the prognostic value of PIG11 for HCC patients, and the
      biological functions on the apoptosis of HepG2 cells. We discovered that high
      PIG11 expression was negatively associated with certain clinical characteristics,
      and higher expression of PIG11 resulted in better prognosis of patients with HCC.
      PIG11 over-expression induced HepG2 cell apoptosis through the mitochondrial
      pathway, and reactive oxygen species played a regulatory role in this process.
      Hence, PIG11 may act as a candidate liver tumor suppressor and exhibit potential
      as a novel prognostic biomarker for HCC.

PMID- 30241047
TI  - Local treatment of the dental caries using nanomaterials.
AB  - Targeted therapy as well as reduced adverse effects are the advantages of local
      drug delivery in dental caries. The application of nanotechnology in this context
      has gained increasing momentum during last years. A literature search here has
      provided a brief overview to present the recent developments in using
      nanoparticles for local treatment of dental caries. Nanoparticles as delivery
      systems, can entrap substances/drugs and use the advantages of small size and
      better penetration. They can also profit from biomimetic approaches to provide
      more effective treatment. Thoroughly, nanotechnology-based treatment of dental
      caries in situ, may introduce a novel aid in the field of dentistry.

PMID- 30241048
TI  - Cadmium nitrate-induced neuronal apoptosis is protected by N-acetyl-l-cysteine
      via reducing reactive oxygen species generation and mitochondria dysfunction.
AB  - Cigarette smoking is a well-established risk factor for various diseases, such as
      cardiovascular diseases, neurodegeneration, and cancer. Cadmium nitrate
      (Cd(NO3)2) is one of the major products from the cigarette smoke. Up to now, no
      supporting evidence on Cd(NO3)2-induced apoptosis and its related working
      mechanism in neurons has been found. In present study, the mode of cell death,
      caspase activities, reactive oxygen species (ROS) generation, and mitochondrial
      dysfunction in N2a cells, which are neuron-like cells, were assessed by Annexin V
      FITC and PI assays, caspase fluorometric assay, DCFH-DA fluorescence assay, and
      JC-1 fluorescence assay respectively. The results showed that not only Cd(NO3)2
      induced apoptosis and necrosis but also the activities of caspase-3 and -9
      expressed in a concentration-dependent manner. In addition, Cd(NO3)2 also induced
      both mitochondrial dysfunction and ROS generation in a concentration-dependent
      manner. All these indicated that in N2a cells parallel trends could be observed
      in apoptosis, caspase-3 and -9 activities, mitochondrial dysfunction, and ROS
      generation when induced by Cd(NO3)2. Furthermore, Cd(NO3)2-induced apoptosis,
      caspases activities, mitochondrial dysfunction, and ROS generation were reduced
      by N-acetyl-l-cysteine (NAC). These results indicated that Cd(NO3)2-induced
      neuronal apoptosis was reduced by NAC via intrinsic apoptotic caspase cascade
      activities and their up-stream factors, including mitochondrial dysfunction and
      ROS generation.

PMID- 30241049
TI  - Moringa oleifera and their phytonanoparticles: Potential antiproliferative agents
      against cancer.
AB  - Cancer is classified as one of the leading causes of global mortality. It has
      affected millions of people, often with poor prognosis. Having severe side
      effects with conventional chemotherapy, alternate drugs and therapies are
      actively being investigated. There is a need for innovative drug discovery and
      design as existing cancer therapies are costly and not readily available.
      Ayurveda and traditional medicine have utilised natural resources such as plants
      and trees as part of their regime to treat various illness and diseases with
      positive outcomes. One such tree is Moringa oleifera (MO). Almost all parts have
      shown to be effective against several ailments including cancer which was
      attributed to the bioactive constituents. Targeted therapies had led to the
      development of nanoparticles which are extremely effective in various biomedical
      applications due to their small size. Green synthesis of gold nanoparticles have
      great potential as naturally occurring plants and trees such as MO can be used in
      the synthesis process. The resultant gold phytonanoparticles are useful in cancer
      therapies with improved survival rates and quality of life. The review highlights
      the importance of MO in natural medicine, synthesis of phytonanoparticles and the
      fundamental role as a potential antiproliferative agent against cancer.

PMID- 30241050
TI  - Capn4 expression is modulated by microRNA-520b and exerts an oncogenic role in
      prostate cancer cells by promoting Wnt/beta-catenin signaling.
AB  - Accumulating evidence reports that Capn4 plays an important role in the
      development and progression of various malignant cancers. However, whether Capn4
      is involved in prostate cancer remains unclear. Therefore, the aim of this study
      was to investigate the expression, biological function and regulatory mechanism
      of Capn4 in prostate cancer. Herein, we found that Capn4 was highly expressed in
      prostate cancer cell lines compared with normal prostate cells. Capn4 gene
      silencing markedly suppressed the growth, invasion and Wnt/beta-catenin signaling
      of prostate cancer cells, whereas Capn4 overexpression showed an oncogenic
      effect. Moreover, silencing of beta-catenin significantly blocked the oncogenic
      effect of Capn4 overexpression. Bioinformatics analysis predicted that Capn4 was
      a potential target gene of microRNA-520b (miR-520b), which has been reported as a
      tumor suppressive miRNA in various cancers. The dual-luciferase reporter assay
      confirmed that miR-520b directly bound to the 3'-untranslated region of Capn4.
      Real-time quantitative PCR and Western blot analysis showed that miR-520b
      negatively regulated Capn4 expression in prostate cancer cells in vitro.
      Furthermore, we found that miR-520b was significantly downregulated in prostate
      cancer cell lines and tissues. In addition, miR-520b expression was inversely
      correlated with Capn4 expression in prostate cancer clinical specimens.
      Overexpression of miR-520b mimicked the tumor suppressive effect of Capn4 siRNA,
      whereas inhibition of miR-520b had an oncogenic effect. Restoration of Capn4
      significantly blocked the antitumor effect of miR-520b in prostate cancer cells.
      Overall, our findings demonstrate an oncogenic role of Capn4 in prostate cancer
      and show that its expression is epigenetically regulated by miR-520b. Our results
      reveal that suppression of Capn4 by miR-520b inhibits the growth and invasion of
      prostate cancer cells associated with downregulated Wnt/beta-catenin signaling,
      indicating an important role of the miR-520b/Capn4/Wnt/beta-catenin regulation
      axis in the molecular pathogenesis of prostate cancer. Our study suggests that
      miR-520b and Capn4 may represent potential and novel therapeutic targets for
      prostate cancer.

PMID- 30241051
TI  - Equine suspensory ligament and tendon explants cultured with platelet-rich gel
      supernatants release different anti-inflammatory and anabolic mediators.
AB  - The aim of this study was to evaluate the release of pro- and anti-inflammatory
      as well as anabolic mediators stimulated by a leukocyte-reduced platelet-rich gel
      supernatant (Lr-PRGS) and a leukocyte-reduced plasma supernatant (Lr-PL) at two
      concentrations (25 and 50%) on normal equine suspensory ligament explants (SLEs)
      and tendon explants (TEs). SLEs and TEs from six horses were independently
      incubated for 48 h with Lr-PRGS and Lr-PL at concentrations of 25 and 50%,
      respectively. Samples were collected from the incubated tissues at 1 h and 48 h,
      which were employed for ELISA determination of interleukin 1 beta (IL-1beta),
      tumor necrosis factor alpha (TNF-alpha),  IL-4, IL-1 receptor antagonist (IL
      1ra), platelet-derived growth factor isoform BB (PDGF-BB), transforming growth
      factor beta-1 (TGF-beta1, and hyaluronic acid (HA). Overall, 50% Lr-PRGS induced
      significantly less IL-1beta release than the other hemoderivatives in both
      tissues. At 48 h, both Lr-PRGS and 25% Lr-PL induced significantly higher TNF
      alpha concentrations in SLEs when compared to TEs, whereas both Lr-PRGS
      concentrations induced significantly higher IL-4 concentrations in SLEs in
      comparison to TEs. IL-1ra release was not different between tissues. However,
      this cytokine was significantly higher in tissue explants cultured with both Lr
      PRGS concentrations. HA concentration was lower in tissue explants cultured with
      all hemoderivatives at two concentrations when compared to the control group. The
      positive effects observed for ligaments and tendons treated with Lr-PRGS may be
      mediated by the inhibition of IL-1beta release of and increased release of IL-4
      and IL-1ra. Furthermore, PDGF-BB could be a polypeptide responsible for mediating
      the release of anti-inflammatory cytokines in SLEs and TEs incubated with Lr
      PRGS.

PMID- 30241052
TI  - Psychiatric disorders and trauma history in patients with pure PNES and patients
      with PNES and coexisting epilepsy.
AB  - Several studies found high prevalence rates of psychiatric disorders in patients
      with pure psychogenic nonepileptic seizures (PNES). Traumatic experiences were
      also reported to be elevated in patients with PNES and were discussed as a
      crucial risk factor for the development of PNES. Much less is known about
      psychiatric comorbidities and specifically, about trauma history in patients with
      PNES and coexisting epilepsy. Here, we aimed at directly comparing psychiatric
      disorders and traumatic life experiences in patients with pure PNES and in
      patients with PNES and coexisting epilepsy. We assessed the presence of current
      axes I and II disorders in 109 patients with either pure PNES (n = 67) or with
      PNES + epilepsy (n = 42) by using structured clinical interviews. We also
      compared the trauma histories by using the posttraumatic diagnostic scale (PDS)
      as an interview and the extent of physical, sexual, and emotional childhood
      maltreatment measured with the Childhood Trauma Questionnaire (CTQ). Patients of
      both groups had very high rates of psychiatric disorders: 79.1% of the patients
      with pure PNES and 76.2% of the patients with PNES + epilepsy had at least one
      psychiatric disorder. The frequencies of psychiatric disorders did not differ
      between groups. However, there was a trend towards higher rates of posttraumatic
      stress disorder (PTSD) in patients with PNES (32.9%) compared with patients with
      PNES + epilepsy (16.7%). In both groups, the proportion of patients who recalled
      traumatic events in the PDS was high (72.6% in the patients with pure PNES, 64.3%
      in the patients with PNES + epilepsy) and did not differ significantly between
      groups. The age at first traumatization, the types of trauma events experienced,
      the number of patients with single traumatization, and those with repeated
      traumatic experiences also did not differ between groups. We found high
      frequencies of childhood maltreatment in both groups. Our findings show that
      patients with PNES and patients with PNES and coexisting epilepsy could neither
      be differentiated by the amount of psychiatric additional disorders nor by the
      nature and extent of trauma and maltreatment experiences. Our results suggest
      that patients with PNES + epilepsy rather resemble patients with pure PNES than
      patients with epilepsy in respect to psychopathological characteristics and
      adverse life experiences. Trauma and maltreatment history are therefore assumed
      to be predisposing factors to PNES in both patients with pure PNES and patients
      with PNES and coexisting epilepsy.

PMID- 30241053
TI  - Do mentalization skills affect the perception of stigma in patients with
      epilepsy?
AB  - PURPOSE: We aimed to study the relationship between the mentalizing ability and
      stigma in patients with epilepsy. METHODS: Patients with epilepsy were
      administered the following battery of tests: Mini-International Neuropsychiatric
      Interview (MINI) form, Reading the Mind in the Eyes Test (Eyes Test), Stigma
      Scale of Epilepsy (SSE), Internalized Stigma of Mental Illness (ISMI) Scale, Beck
      Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). RESULTS: Assessment
      of an association between the Eyes Test score, ISMI Scale total score, and
      subscale scores revealed a negative significant correlation of Eyes Test scores
      with approval of stereotypes, perceived discrimination, stigma resistance, and
      total score. Eyes Test score and BDI scores appears to be significant predictor
      of internalized stigma among the clinical variables that were studied. A positive
      significant correlation was detected between BDI score and alienation, perceived
      discrimination, and total score. CONCLUSION: The presence of a correlation
      between the mentalization and stigma perception in our study demonstrates that
      these two concepts are connected and that this connection needs further study. In
      particular, mentalization-based therapy can have an effect on the reduction of
      the stigma perceptions and in this way can improve the course of the disease,
      potentially improving the patients' quality of life.

PMID- 30241054
TI  - Pharmacotherapy in patients with epilepsy and psychosis.
AB  - The recognition and treatment of psychosis in persons with epilepsy (PWE) is
      recommended with the apparent dilemma between treating psychosis and opening the
      possibility of exacerbating seizures. The pooled prevalence estimate of psychosis
      in PWE is 5.6%. It has been proposed that a 'two hit' model, requiring both
      aberrant limbic activity and impaired frontal control, may account for the wide
      range of clinical phenotypes. The role of antiepileptic drugs in psychosis in PWE
      remains unclear. Alternating psychosis, the clinical phenomenon of a reciprocal
      relationship between psychosis and seizures, is unlikely to be an exclusively
      antiepileptic drug-specific phenomenon but rather, linked to the neurobiological
      mechanisms underlying seizure control. Reevaluation of antiepileptic treatment,
      including the agent/s being used and degree of epileptic seizure control is
      recommended. The authors found very few controlled studies to inform evidence
      based treatment of psychosis in PWE. However, antipsychotics and benzodiazepines
      are recommended as the symptomatic clinical treatments of choice for postictal
      and brief interictal psychoses. The general principle of early symptomatic
      treatment of psychotic symptoms applies in epilepsy-related psychoses, as for
      primary psychotic disorders. In the authors' experience, low doses of
      antipsychotic medications do not significantly increase clinical risk of seizures
      in PWE being concurrently treated with an efficacious antiepileptic regimen.

PMID- 30241055
TI  - Levetiracetam circulating concentrations and response in status epilepticus.
AB  - INTRODUCTION: Intravenous levetiracetam (LEV) is broadly used in the treatment of
      status epilepticus (SE). A loading dose is usually infused, aiming to reach
      quickly the range of plasma concentrations considered as therapeutic (12-46
      mg/l). The aim of the study was to evaluate the response to LEV in SE, correlated
      exposure assessed by plasma concentration monitoring, as well as calculated
      exposure parameters. MATERIALS & METHODS: We retrospectively analyzed a SE
      registry, including patients since 2015 with at least one available LEV plasma
      level measured less than 36 h after loading. A Bayesian maximum likelihood
      approach based on a population pharmacokinetic model was used to estimate LEV
      exposure parameters. We compared plasma levels and pharmacokinetics parameter
      estimates between responders and nonresponders. Therapeutic response was defined
      as SE cessation within 24 h following LEV introduction without a need for
      additional antiepileptic drug (AED). RESULTS: We included 29 patients (45 plasma
      levels). Variability was salient in LEV loading doses (ranging between 17 and 38
      mg/kg) and monitoring practice. There was no difference in median plasma
      concentrations (19.5 versus 21.5 mg/l; p = 0.71), median estimated LEV exposure
      (25.8 versus 37.0 mg/l; p = 0.61), peak (30.4 versus 41.5 mg/l; p = 0.36), or
      residual levels after loading dose (14.4 versus 20.5 mg/l; p = 0.07) between
      responders and nonresponders. CONCLUSIONS: Levetiracetam exposure does not seem
      to differ significantly between responders and nonresponders; greater exposure
      was not associated with better outcome. Loading doses of 30 mg/kg seem, however,
      appropriate to quickly reach the target exposure level. The short LEV half-life
      makes standardized sampling measurement necessary to obtain directly
      interpretable LEV levels.

PMID- 30241056
TI  - Burden of illness in patients with possible Lennox-Gastaut syndrome: A
      retrospective claims-based study.
AB  - OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe and treatment-resistant
      epilepsy syndrome characterized by multiple subtypes of intractable seizures,
      moderate to severe cognitive impairment, and slow spike-wave complexes on
      electroencephalographic (EEG) recordings. Lennox-Gastaut syndrome is also
      associated with increased risk for injury, reduced quality of life, long-term
      disability, and early mortality. By evaluating private and public US medical
      insurance claims, we quantified healthcare utilization and direct costs in
      patients with possible LGS. METHODS: Commercial and Medicaid insurance claims
      (Truven Health Analytics) from October 2010 to September 2015 were queried to
      identify patients with intractable epilepsy, intellectual disability, >=1
      prescription for selected antiepileptic drugs (AEDs), and >=2 years of continuous
      enrollment. To identify patients with LGS in the absence of a specific
      International Classification of Diseases ICD-9 diagnosis code, current or prior
      rufinamide use was selected as a disease indicator of LGS per previously
      published methodology. Characteristics significantly predictive of rufinamide use
      were identified with multivariate regression by comparing groups with and without
      LGS, then assessed in non-rufinamide users fulfilling all other inclusion
      criteria. Controls without epilepsy, seizures, or prescriptions for selected AEDs
      were matched to patients with possible LGS by age, gender, US region, and dates
      of insurance coverage. Average healthcare utilization and costs per patient per
      year (PPPY) were evaluated for a 2-year postindex period and compared between the
      cohort with LGS and controls by insurance type. Costs were normalized to 2017
      dollars at 3% per annum. RESULTS: In the study, 6019 patients with possible LGS
      (53% male, mean age of 13 years, in both insurance groups) were identified: 2270
      with commercial insurance and 3749 with Medicaid. The cohort with LGS used >8
      times more services and >7 times more drugs than controls (all p < 0.001) in both
      insurance groups. The biggest contributors to service use PPPY were outpatient
      physician visits and home health services in the commercial-insured cohort with
      LGS and other outpatient visits and home health services in the Medicaid-insured
      cohort with LGS. Average total costs PPPY (services + drugs) were significantly
      higher for the cohort with LGS vs. controls: $65,026 (SD $34,324) vs. $2442 (SD
      $10,670) for commercial-insured and $63,930 (SD $45,761) vs. $3849 (SD $13849)
      for Medicaid-insured patients. The biggest cost contributors PPPY were inpatient
      care in the commercial-insured cohort with LGS and home health services in the
      Medicaid-insured cohort with LGS. CONCLUSIONS: Patients with possible LGS have
      significantly higher healthcare utilization and costs than patients without
      epilepsy or seizures. Our results suggest that direct costs associated with LGS
      are substantial and highlight the need for new and effective treatments.

PMID- 30241057
TI  - Explanatory factors of adherence to community-based management of epilepsy in Lao
      PDR.
AB  - RELEVANCE: A low level of knowledge about epilepsy among health workers, a
      context of stigmatizing sociocultural beliefs, and a low availability of
      antiepileptic drugs in Lao People's Democratic Republic (PDR) are major gaps in
      the medical management of people with epilepsy in this country. OBJECTIVES: The
      principal objective of the study was to identify the associated factors of
      adherence to community healthcare structures in Lao PDR. Specific objectives were
      to evaluate patients' adherence status, practices and knowledge about epilepsy
      and its care, and factors influencing decision-making on therapeutic
      interventions. MATERIALS AND METHODS: The study was an observational cross
      sectional survey about knowledge, attitudes, and practices, handled from February
      to May 2016. Eighty-seven people with epilepsy were identified in two areas in
      the periphery of Vientiane Capital through an active screening in villages and
      homes. Semidirective questionnaires were conducted to collect quantitative and
      qualitative data. Quantitative analysis included a comparison of adherent vs.
      nonadherent people with epilepsy, using Chi-square or Fisher's test. Advanced
      qualitative lexical analysis was carried out on the open-ended questions.
      RESULTS: Sixty-two people with epilepsy were included and the adherence rate to
      community care was 67.7%. The only sociodemographic variable that differed
      significantly between adherent and nonadherent members was the income level (p =
      0.015): the wealthiest class of people with epilepsy did not adhere to community
      healthcare. Eleven percent of people with epilepsy thought that epilepsy was
      contagious, 80.6% that medication may reduce epilepsy seizure rates, and 33.9%
      that it was possible to cure epilepsy permanently. Physicians informed about the
      disease in 69.0% of adherent people with epilepsy and in 40.0% of nonadherent
      ones (p = 0.029), whereas villagers were involved in 29.0% and 50.0% of cases,
      respectively. There was a significant difference between the two groups for the
      prescribed antiepileptic drugs (p = 0.012): phenobarbital covered 73.8% of
      adherent people with epilepsy but only 40% of nonadherent ones. Half of
      nonadherent people with epilepsy went regularly to a central hospital in the
      Vientiane Capital, 15.0% went to Thailand, and 10.0% practiced self-medication in
      occasional mobilities. CONCLUSION: A wider range of antiepileptic drugs at a
      reduced cost and the promotion of adherence to community healthcare would allow a
      better management of people with epilepsy in Lao PDR.

PMID- 30241058
TI  - Maintenance mechanisms of circuit-integrated axons.
AB  - Adult, circuit-integrated neurons must be maintained and supported for the life
      span of their host. The attenuation of either maintenance or plasticity leads to
      impaired circuit function and ultimately to neurodegenerative disorders. Over the
      last few years, significant discoveries of molecular mechanisms were made that
      mediate the formation and maintenance of axons. Here, we highlight intrinsic and
      extrinsic mechanisms that ensure the health and survival of axons. We also
      briefly discuss examples of mutations associated with impaired axonal maintenance
      identified in specific neurological conditions. A better understanding of these
      mechanisms will therefore help to define targets for therapeutic interventions.

PMID- 30241059
TI  - Passive samplers in sewers and rivers with highly fluctuating micropollutant
      concentrations - Better than we thought.
AB  - Considerable pollutant loads can enter surface waters during rain events. Three
      factors challenge quantification of these pollutant fluxes using traditional
      sampling methods: (i) concentration fluctuations; (ii) unknown event duration;
      and (iii) placement, operation, and maintenance of equipment. Passive samplers
      offer the advantage of sampling in a continuous mode without power supply.
      However, variable uptake rates due to environmental factors and desorption in the
      case of fluctuating concentrations can affect the accuracy of time-weighted
      average (TWA) concentration estimates. While uncertainties related to
      environmental factors could be accounted for with additional effort, we can
      neither control nor quantify the concentration variability. We present measured
      and modelled concentration profiles at high temporal resolution and provide a
      systematic approach to assessing deviations from true TWA concentration due to
      fluctuating concentration profiles. We evaluate sampling of sewer overflows (0.3
      14 h) with Chemcatcher and 1-week sampling in rivers. The uncertainty due to
      fluctuating concentrations is small, and other factors such as chemical analyses
      and sampler calibration have a similar or higher impact. The uncertainty due to
      fluctuations clearly increases with the sampling duration, particularly when
      exceeding the half-life of equilibrium. We conclude that passive sampling can
      also be used in wastewater systems with potentially high concentration
      variations.

PMID- 30241060
TI  - Synthesis of belt-like bismuth-rich bismuth oxybromide hierarchical
      nanostructures with high photocatalytic activities.
AB  - Belt-like Bi4O5Br2 hierarchical nanostructures were synthesized through a facile
      one-step hydrolysis method performed at different temperatures (0-160  degrees
      C), using belt-like bismuth subsalicylate as the morphological template and
      bismuth source. The belt-like Bi4O5Br2 samples are found to be composed of
      irregular single-crystal nanosheets with highly exposed (0 1 0) facets. The
      photocatalytic activity of the belt-like Bi4O5Br2 was evaluated by referring to
      the degradation of salicylic acid and resorcinol under visible-light irradiation,
      and compared with those of belt-like BiOBr dominantly exposing (0 1 0) facets and
      plate-like Bi4O5Br2 dominantly exposing (1 0 -1) facets. The belt-like Bi4O5Br2
      shows higher photocatalytic activity than belt-like BiOBr owing to the more
      negative conduction band potential, narrower band gap, and larger specific
      surface area (SBET) of the former. In addition, the belt-like Bi4O5Br2 also
      exhibits higher photocatalytic activity than plate-like Bi4O5Br2, mainly due to
      the larger SBET of the former. Interestingly, the belt-like Bi4O5Br2 obtained at
      room temperature (25  degrees C) shows the highest photocatalytic activity,
      because it has the largest SBET. Moreover, the as-synthesized belt-like Bi4O5Br2
      exhibits excellent stability and reusability. This study provides a simple,
      energy-saving route for the synthesis of belt-like bismuth-rich bismuth oxyhalide
      hierarchical nanostructures.

PMID- 30241061
TI  - Nickel cobaltite nanosheets coated on metal-organic framework-derived mesoporous
      carbon nanofibers for high-performance pseudocapacitors.
AB  - Core-shell structured carbon nanofiber@metal oxide is one of the most promising
      hybrid electrodes as supercapacitors, in which the pseudocapacitive metal oxides
      can be fully exerted and stabilized on the carbonaceous scaffolds. However,
      facile fabrication of mesoporous carbon nanofibers and integration of them with
      metal oxides are challenging. Herein, we report a new type of mesoporous carbon
      nanofibers (MCNs), derived from zinc-trimesic acid fibers, acting as the
      scaffolds to anchor nickel cobaltite (NiCo2O4) nanosheets after surface O
      functionalization. The resultant core-shell OMCN@NiCo2O4 nanostructure is
      demonstrated by scanning electron microscope (SEM), elemental mapping, bright
      field/high-resolution transmission electron microscope (TEM), selected area
      electron diffraction (SAED) studies. The anchored NiCo2O4 nanosheets are dense
      (97.4%), and have a strong interaction with OMCN, as revealed by X-ray
      diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric
      analysis (TGA) and H2-temperature programmed reduction (H2-TPR) techniques. As
      expected, the OMCN@NiCo2O4 is highly efficient, showing a high specific
      capacitance of 1631 F g-1 at the current density of 1 A g-1, excellent rate
      capability and superior cycling stability up to 5000 cycles within a high
      capacitance retention ratio of 94.5%. This research opens the avenue to fabricate
      high-efficiency carbon-metal oxide electrodes using metal-organic framework fiber
      derived mesoporous carbon nanofibers and integration of them with NiCo2O4
      nanosheets by increasing the interfacial interaction.

PMID- 30241062
TI  - Solid-state chemical fabrication of one-dimensional mesoporous beta-nickel
      molybdate nanorods as remarkable electrode material for supercapacitors.
AB  - Simple solid-state chemical reaction was adopted to synthesize NiMoO4
      nanomaterials with different crystal phase without the use of organic solvent or
      templating agent. The as-prepared NiMoO4.xH2O, alpha-NiMoO4 and beta-NiMoO4
      nanostructures were investigated as the electrode materials for supercapacitors.
      The beta-NiMoO4 nanorods were composed of the nanoparticles, which exhibited
      relatively high specific capacitances about 1415 F g-1 at a charge density of 1 A
      g-1, 80.2% of the initial reversible capacity was maintained after 1000 cycles.
      The beta-NiMoO4//rGO asymmetric supercapacitor (ASC) system was assembled in
      serials, which displayed high specific energy density of 29.3 Wh kg-1 at a high
      power density of 187 W kg-1. This ASC system can drive the light-emitting diode
      (LED) effectively and give out light about 40 min, even easily light two LEDs in
      serials for 20 min. The remarkable electrochemical performances make the as
      prepared NiMoO4 nanostructures an excellent candidate as electrode materials for
      advanced supercapacitors.

PMID- 30241064
TI  - Co-pyrolysis of lignin and plastics using red clay as catalyst in a micro
      pyrolyzer.
AB  - In the current study, low-density polyethylene and polystyrene were co-pyrolyzed
      with dealkaline lignin in a micro-reactor at 500  degrees C with and without low
      cost red clay catalyst. The products were analyzed with GC-MS/FID to quantify
      phenolic compounds, alkanes and alkenes. The synergistic effect between plastics
      and lignin was studied by comparing the carbon yield of compounds from co
      pyrolysis with that from individual pyrolysis. The co-pyrolysis of lignin and
      polystyrene was also performed at 600, 700 and 800  degrees C to examine the
      effect of pyrolysis temperature. The study explores a novel approach to enhance
      lignin depolymerization with red clay catalyst while utilizing waste plastics.

PMID- 30241063
TI  - Bioelectricity generation using microalgal biomass as electron donor in a bio
      anode microbial fuel cell.
AB  - In this study, microalgal biomass waste (Chlorella regularis) was treated while
      simultaneously producing bioelectricity in a microbial fuel cell (MFC). Algal
      biomass was the sole electron donor and was enriched with easily biodegradable
      proteins (46%) and carbohydrates (22%). The generated power density was 0.86 W/m2
      and the columbic efficiency reached ~61.5%.The power generation could be further
      increased to 1.07 W/m2 by using a biomass waste concentration enhancement
      strategy with maximum chemical oxygen demand (COD) removal of ~65.2%. Via direct
      comparison, the power generation and COD removal capability of the algal-fed MFC
      was close to that of the commercial acetate-fed MFC. The algae-fed MFC presented
      superior electrochemical characteristics that were attributed to the complicated
      composition of the biomass anolyte. It possessed a multiple anode respiring
      bacterial group and diverse microbial community. Hence, this study provides a new
      strategy for the utilization of microalgal biomass as a bioresource.

PMID- 30241065
TI  - Isolation of C-phycocyanin from Spirulina platensis microalga using Ionic liquid
      based aqueous two-phase system.
AB  - An aqueous two-phase system (ATPS) with ionic liquids (ILs) was used for the
      isolate of C-phycocyanin (CPC) from Spirulina platensis microalga. Various
      imidazolium ILs and potassium salts were studied. The effect of ILs-ATPS on the
      extraction efficiency of CPC was also studied. The experimental parameters like
      pH, loading volume, algae concentration, temperature, and alkyl chain length of
      IL were well-covered in this report. The experimental results showed that the
      extraction efficiency, the partition coefficient, and the separation factor for
      CPC were 99%, 36.6, and 5.8, respectively, for an optimal pH value of 7 and a
      temperature of 308 K. The order of extraction efficiency for CPC using IL-ATPS
      was: 1-octyl-3-methylimidazolium bromide (C8MIM-Br) > 1-hexyl-3-methylimidazolium
      bromide (C6MIM-Br) > 1-butyl-3-methylimidazolium bromide (C4MIM-Br). The
      isolation process followed the pseudo second-order kinetic model and the
      thermodynamic results were obviously spontaneous.

PMID- 30241066
TI  - Effects of endogenous inhibitors on the evolution of antibiotic resistance genes
      during high solid anaerobic digestion of swine manure.
AB  - Livestock manure is a reservoir of antibiotic resistance genes (ARGs). The
      endogenous inhibitors that emerge during high solid anaerobic digestion (HSAD)
      greatly influence the bioprocess performance and the ARGs. The effect of
      endogenous inhibitors including volatile fatty acids (VFAs) and free ammonia (FA)
      on the ARG occurrences during HSAD of swine manure was investigated in this
      study. The ARG properties during HSAD (8%-14% total solids (TS)) largely differed
      from the low TS control (4%). The endogenous inhibitors and microbial communities
      greatly contributed to the three-phase changes in ARGs. The concentrations of
      VFAs and abundances of Proteobacteria and intI1 were correlated with the changes
      in ARGs. FA inhibition and VFA accumulation (especially propionate) delayed and
      restricted the decline of ARGs. The relatively slow rate of changes in ARGs and
      high ARGs in the end product suggested the high risk of the HSAD digestate for
      land application.

PMID- 30241067
TI  - A novel strategy to enhance biohydrogen production using graphene oxide treated
      thermostable crude cellulase and sugarcane bagasse hydrolyzate under co-culture
      system.
AB  - Graphene oxide (GO) treated thermostable crude cellulase has been obtained via
      fungal co-cultivation of strain Cladosporium cladosporioides NS2 and Emericella
      variecolor NS3 using mix substrate of orange peel and rice straw under solid
      state fermentation (SSF). Enzyme activity of 60 IU/gds FP, 300 IU/gds EG and 400
      IU/gds BGL are recorded in the presence of 1.0% GO in 96 h. This crude enzyme
      showed 50  degrees C as optimum incubation temperature, thermally stable at 55 
      degrees C for 600 min and stability in the pH range 4.5-8.0. Further, 70.04 g/L
      of sugar hydrolyzate is obtained from enzymatic conversion of 3.0% alkali pre
      treated baggase using GO treated crude cellulase. Finally, 2870 ml/L cumulative
      biohydrogen production having bacterial biomass ~2.2 g/L and the complimentary
      initial pH 7.0 is recorded from sugar hydrolyzate via dark fermentation using co
      culture of Clostridium pasteurianum (MTCC116) and a newly isolated Bacillus
      subtilis PF_1.

PMID- 30241068
TI  - Training history constrains postural sway dynamics: A study of balance in
      collegiate ice hockey players.
AB  - BACKGROUND: Balance and postural control are integral to training and sport
      performance. Demands on posture are contextual and vary in different ways
      depending on the specific physical activity. RESEARCH QUESTION: The purpose of
      this study was to examine the possibility that sustained exposure to
      environmental constraints, through specific sport participation, might lead to a
      persistent modification of postural control. METHODS: Double and single-leg
      postural sway were compared between ice hockey players, American football players
      and physically active college students. Data from 30 s trials were analyzed using
      traditional postural sway measures of range and pathlength of the center of
      pressure, as well as with Sample Entropy (SEn), in both mediolateral (ML) and
      anteroposterior (AP) directions. RESULTS: Each group displayed unique postural
      sway characteristics. During single-leg stance, ice hockey players show
      significantly different ML pathlength and ML and AP SEn from the physically
      active college students (all p < 0.05), and significantly different ML and AP
      pathlength and AP SEn from the American football players (all p < 0.05). The
      American football players and the physically active college students differed for
      all single-legged conditions (all p < 0.05). SIGNIFICANCE: This suggests that the
      organization and development of postural sway is not only context dependent but
      also influenced by training history; supporting the idea that balance training
      for sport should be designed with regards to sport specific conditions.

PMID- 30241069
TI  - Hybrid catalyst cascade architecture enhancement for complete ethanol
      electrochemical oxidation.
AB  - MWCNT-COOH, TEMPO-modified linear poly(ethylenimine), and alcohol (ADH) and
      aldehyde (AldDH) dehydrogenase immobilization on electrode surfaces yields a
      hybrid, tri-catalytic architecture that can catalyze complete ethanol electro
      oxidation. The chromatographic results obtained for the tri-catalytic hybrid
      electrode system show that ethanol is totally oxidized to CO2 after 12 h of
      electrolysis, confirming that organic oxidation catalysts combined with enzymatic
      catalysts enable collection of up to 12 electrons from ethanol. The Faradaic
      efficiency lies above 60% for all of the electrode systems investigated herein.
      Overall, this study illustrates that surface-immobilized, polymer hydrogel-based
      hybrid multi-catalytic systems exhibit high oxidation rates and constitute a
      simple methodology with useful application in the development of enzymatic
      biofuel cells.

PMID- 30241070
TI  - Application of GC-MS technique for the determination of homocysteine thiolactone
      in human urine.
AB  - It is well established that homocysteine thiolactone (HTL) is associated with
      some health disorders, including cardiovascular diseases. HTL is a by-product of
      sulfur metabolic cycle. So far, its presence has been confirmed in human plasma
      and urine. It has been also shown that a vast majority of HTL is removed from
      human body through kidney. Thus, the aim of the current investigations has been
      the identification, separation and quantification of HTL in urine samples. For
      the first time a cheap, reliable and robust GC-MS method was developed for the
      determination of HTL in human urine in the form of its volatile isobutyl
      chloroformate derivative. Separation of the analyte and internal standard
      (homoserine lactone (HSL)) was achieved in 15 min followed by mass spectrometry
      detection (MS). Isocratic elution was accomplished with helium at a flow rate of
      1 mL min-1 and a gradient of the column temperature was concomitant with the
      analysis. The mass spectrometer was set to the electron impact mode at 70 eV. The
      ion source, quadrupole and MS interface temperatures were set to 230  degrees C,
      150  degrees C and 250  degrees C, respectively. Elaborated analytical procedure
      allows quantification of analyte in a linear range of 0.01-0.20 nmol mL-1 urine.
      The LOQ and LOD values were 0.01 and 0.005 nmol mL-1, respectively. The method
      accuracy ranged from 98.0% to 103.2%, while precision varied from 6.4% to 9.5%
      and from 10.7% to 16.9% for intra- and inter-day measurements, respectively.
      Finally, the method has been successfully implemented in the analysis of 12 urine
      samples donated by apparently healthy volunteers. Concentration of HTL ranged
      from <LOQ to 163 pmol mL-1 urine (0.51 to 13.1 MUmol mol-1 Crn).

PMID- 30241071
TI  - Composition analysis and antioxidant activity of essential oils, lipids and
      polysaccharides in different phenotypes of Lepidium meyenii.
AB  - The phenotypes of Lepidium meyenii (Maca) relate to their difference of chemical
      compositions and biological activities. Essential oils, lipids and
      polysaccharides are the main active components in Maca, all of which showed
      potential antioxidant effect. The essential oil, lipid and polysaccharide
      compositions were analyzed by GC-MS after the samples were properly pre-treated
      from yellow, red and black Maca. The antioxidant properties of the three types of
      components were examined using the DPPH scavenging assay. The correlation of main
      compositions and the antioxidant activities was evaluated by a statistical
      method. In Maca essential oil, lipid and polysaccharide samples, thirty volatile
      compounds, twenty-nine fatty acids and six monosaccharides had been detected, in
      which benzeneacetonitrile, unsaturation fatty acids and mannose were predominant
      ingredients, respectively. In three types of components, the DPPH scavenging
      effect of essential oil was stronger. All of black Maca essential oil, lipid and
      polysaccharide showed higher effect than yellow and red phenotype. The total
      activity of the three types of components showed about 60% of the antioxidant
      activity of entire Maca. Canonical correlation analysis (CCA) results showed that
      four essential oils, three fatty acids and four monosaccharaides were positively
      related to the antioxidant activity. The research is helpful to address the
      quality attributes and the comprehensive application of different phenotypes of
      Maca.

PMID- 30241073
TI  - Characteristic volatiles fingerprints and changes of volatile compounds in fresh
      and dried Tricholoma matsutake Singer by HS-GC-IMS and HS-SPME-GC-MS.
AB  - The present study was to analyze the water dynamics of Tricholoma matsutake
      Singer during hot air drying by low-field nuclear magnetic resonance (LF-NMR) and
      magnetic resonance imaging (MRI), and to investigate the volatile compounds in
      the pileus, upper stipe and lower stipe of fresh and dried Tricholoma matsutake
      Singer by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and
      headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS
      SPME-GC-MS). Fresh samples were dried at 60  degrees C for 12 h. With the T2i
      relaxation times decreasing, the water migrated from the inner toward the
      periphery and then expelled during drying. The characteristic volatiles
      fingerprints of different parts of fresh and dried samples were established by HS
      GC-IMS. The significant differences in volatile compounds were observed among
      different parts of the fresh sample and C8 compounds (70%-97%) were the principal
      components. After drying, the concentration of C8 compounds dramatically
      decreased and some volatile compounds (hexanal, heptanal, 2(5H)-furanone,
      acetophenone, nonanal, benzeneacetaldehyde) were formed. Thus, hot air treatment
      affected the volatile compounds in Tricholoma matsutake Singer.

PMID- 30241072
TI  - Development and validation of an ultra-high performance liquid
      chromatography/triple quadrupole mass spectrometry method for analyzing microbial
      derived grape polyphenol metabolites.
AB  - Accumulating evidence indicates that the health impact of dietary phenolic
      compounds, including the principal grape-derived polyphenols, (+)-catechin and (
      )-epicatechin, is exerted by not only the parent compounds but also their
      phenolic metabolites generated by the gut microbiota. In this work, a new high
      throughput, sensitive and reproducible analytical method was developed employing
      ultra-high performance liquid chromatography coupled with triple quadrupole
      tandem mass spectrometry (UHPLC-QqQ-MS/MS) for the simultaneous analysis of 16
      microbial-generated phenolic acid metabolites (PAMs) along with their precursors,
      catechin and epicatechin. Following optimizing the solvent system, LC conditions
      and MS parameters, method validation was carried out to evaluate the sensitivity,
      selectivity, accuracy and precision of the proposed method, and to ensure
      promising recovery of all analytes extracted from the matrix prior to
      bioanalysis. Results showed that the optimized analytical method allowed
      successful confirmation and quantitation of all analytes under dynamic multiple
      reaction monitoring mode using trans-cinnamic acid-d7 as an internal standard
      (I.S.). Excellent sensitivity and linearity were obtained for all analytes, with
      lower limits of detection (LLODs) and lower limits of quantification (LLOQs) in
      the ranges of 0.225-2.053 ng/mL and 0.698-8.116 ng/mL, respectively. By examining
      blank matrix spiked with standard mixture at different concentration levels,
      promising recoveries at two spiking levels (low level, 91.2-115%; high level 90.2
      121%), and excellent precision (RSD < 10%) were obtained. This method was then
      successfully applied to an in vitro study where catechin/epicatechin-enriched
      broth samples were anaerobically fermented with gut microbes procured from
      healthy human donors. All sources of bacteria employed showed remarkable activity
      in metabolizing grape polyphenols and distinct variations in the production of
      PAMs. The successful application of this method in the in vitro fermentation
      assays demonstrates its suitability for high-throughput analysis of polyphenol
      metabolites, particularly catechin/epicatechin-derived PAMs, in biological
      studies.

PMID- 30241075
TI  - Next generation database search algorithm for forensic mitogenome analyses.
AB  - Mitochondrial DNA (mtDNA) variation is being reported relative to the corrected
      version of the first sequenced human mitochondrial genome. A review of the
      existing literature across disciplines that employ mtDNA demonstrates that
      insertions and deletions are not reported in a standardized way. This may lead to
      false exclusions of identical sequences, unidentified matches in missing persons
      mtDNA databases, biased mtDNA database frequency estimates and overestimation of
      the genetic evidence. Seven years ago we introduced alignment-free database
      search software (SAM) and implemented it into the mtDNA database EMPOP
      (https://empop.online) to produce reliable and conservative frequency estimates
      that are required in the forensic context. However, ambiguity remained in how
      laboratories have been reporting mitotypes, as often more than one single
      alignment of a given mtDNA sequence was feasible. In order to overcome this
      limitation we here describe a concept and provide software for producing stable,
      harmonized phylogenetic alignment of mtDNA sequences for database searches. The
      new software SAM 2 will be made available via EMPOP and provide the user with the
      already established conservative frequency estimates. In addition, SAM 2 offers
      the rCRS-coded haplotype of a given mtDNA sequence following the established and
      widely accepted phylogenetic alignment. This provides the user with feedback on
      how mitotypes are stored in EMPOP and how they should be reported in order to
      harmonize nomenclature. Finally, this approach does not only permit reliable
      mtDNA nomenclature in forensics but invites related disciplines to take advantage
      of a standardized way of reporting mtDNA variation, thus closing the ranks
      between different genetic fields and supporting dialogue and collaboration
      between mtDNA scholars from various disciplines.

PMID- 30241074
TI  - Mechanism of YLTZ on glycolipid metabolism based on UPLC/TOF/MS metabolomics.
AB  - Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by
      dysfunction of glycolipid metabolism. YLTZ is used to treat hyperlipidemia, yet
      its hypolipidemic and hypoglycemic mechanism on T2DM are unknown. Thus,
      UPLC/TOF/MS was applied in this study to identify the potential bio-markers, and
      deduce the possible metabolic pathways. According to bio-indexes, the increased
      blood lipid levels, including TC, TG, LDL and FA, and the decreased HDL, the
      elevated glucose, reduced insulin level and impaired OGTT were observed in
      diabetic rat model. While YLTZ can decrease the lipid levels and glucose content,
      as well as increased insulin standards and improve OGTT. After data from
      UPLC/TOF/MS processed, 17 metabolites were obtained, including phospholipids
      (LPCs, PCs and PGP (18:1)), beta-oxidation production (HAA, VAG and CNE) and
      precursors (THA), bile acid (CA, CDCA and IDCA), hydrolysate of TG (MG (22:4)),
      glycometabolism (G6P), cholesterol-driven synthetics (ADO) and production of
      arachidonate acid (THETA). As a result, YLTZ was able to reduce LPCs, PCs, PGP
      (18:1), HAA, VAG, CNE, CA, ADO and THETA, as well as enhance MG (22:4) and G6P.
      After analyzing results, several metabolic pathways were deduced, which
      containing, cholesterol synthesis and elimination, FA beta-oxidation, TG
      hydrolysis, phospholipids synthesis, glycolysis, gluconeogenesis and
      inflammation. Consequently, YLTZ performed to prohibit the FA beta-oxidation,
      synthesis of cholesterol and phospholipids, gluconeogenesis and inflammation
      level, as well as promote TG hydrolysis, glycolysis and blood circulation. Hence,
      applying metabonomics in TCM research can uncover its pharmacological edges,
      elucidating comprehensively that YLTZ has capacity of hypolipidemic, hypoglycemic
      and promoting blood circulation, matching the effect of removing blood stasis,
      eliminating phlegm and dampness.

PMID- 30241076
TI  - Protection of extractable lipid and lignin: Differences in undisturbed and
      cultivated soils detected by molecular markers.
AB  - Understanding formation of organo-mineral association is crucial for soil organic
      matter (SOM) stabilization. To remove reactive minerals from un-disturbed natural
      soil (NS) and two cultivated soils (dry-farming soil, TD, and terrace paddy soil,
      TP), a 10% HF/1M HCl treatment was applied. The mineral protection of different
      molecular SOM structures before and after cultivation was compared by using
      markers for lipid and lignin. The removal of reactive mineral increased the lipid
      extractability in TD and NS similarly, indicating that the cultivation did not
      reduce the mineral protection; this is attributable to fertilizer application and
      amorphous Fe oxide enrichment. In TP, the extent of lipid protection was lower
      than in TD, demonstrating that the protection depends on the type of cultivation.
      In contrast to lipids, lignin-derived phenols decreased over 80% after acid
      treatment. Furthermore, the ratios of acid to aldehyde in vanillyl ((Ad/Al)V) of
      TD and TP were much higher than in NS, indicating an increased oxidation of
      lignin in cultivated soils. During acid treatment, two distinct layers of soil
      particles were identified: an organic matter (OM)-enriched layer (LOM), and a non
      reactive mineral-enriched layer (LNR) with hardly detectable OC content. However,
      up to 50% of lipids were detected in LNR, indicating that lipids did not
      selectively interact with reactive mineral particles. In TD and TP, (Ad/Al)V
      values were higher in LOM than in LNR, indicating a strong interaction of
      oxidized lignin in LOM. Therefore, the protection of lignin, especially highly
      oxidized lignin, can depend more on reactive minerals than lipid. Promoting the
      formation of organo-mineral complexes is the primary strategy for soil
      management, especially for highly oxidized OM.

PMID- 30241077
TI  - Fly ash toxicity, emerging issues and possible implications for its exploitation
      in agriculture; Indian scenario: A review.
AB  - Fly ash is considered as an environmental hazard worldwide, since it generally
      contain organic pollutants, probable toxic metals like Se, As, B, V, Al, Pb, Hg,
      Cr and radionuclide's Uranium, Thorium. Although fly ash contains toxic
      substances, it also contains most of the oxides and trace elements. Presence of
      oxides contributes to its alkaline pH while trace elements provides nutrients for
      plant growth hence, it is suggested that it can be used in low concentration in
      agriculture sector as well as a soil conditioner as fly ash improves the physico
      chemical and biological properties of contaminated soils. This article presents a
      review on causes of fly ash toxicities due to organic pollutants, heavy metals,
      radioactive elements and environmental issues related to its utilization and
      possibilities of fly ash exploitation in agriculture sector such as
      phytoremediation, bioremediation, reclamation of wasteland and forestry.

PMID- 30241078
TI  - Acute exposure to boron in Nile tilapia (Oreochromis niloticus): Median-lethal
      concentration (LC50), blood parameters, DNA fragmentation of blood and sperm
      cells.
AB  - Recently, Boron (B) contamination of aquatic ecosystem has received considerable
      critical attention due to its toxic effects at high concentrations on plants as
      well as animals. Previous studies on toxic effects of B have not dealt with DNA
      damages in blood and sperm cells of Nile tilapia (Oreochromis niloticus),
      together with blood parameters. This study consisted of two successive
      experiments purposes to determine these findings, including the median-lethal
      concentration (LC50) of B for Nile tilapia. In the first one, at 96 h, LC50 of B
      for Nile tilapia was 141.42 mg L-1 B. In the second one, Nile tilapia were
      treated with five elevated B concentrations (1, 5, 25, 50 and 100 mg L-1 B) and
      hematological, serum biochemical parameters, and DNA damages of Nile tilapia in
      these treatments were determined comparing with the control after 14 days of
      exposure. Hematological parameters (red blood cell count, hematocrit, and
      hemoglobin) were similar to each other in all groups while serum biochemical
      parameters (glucose, total protein, cholesterol, alkaline phosphatase, glutamic
      oxaloacetic transaminase, and glutamic pyruvic transaminase) in B treatments,
      especially in 50 and 100 mg L-1 B groups, were found significantly higher (P <
      0.05). DNA fragmentation was detected in all blood cells in >=25 mg L-1 B
      treatments, while all sperm cells in 100 mg L-1 B treatments. These results
      demonstrated the harmful effects of B at high concentration (50 and 100 mg L-1 B)
      on the DNA integrity of blood and sperm cells, and also the serum biochemical
      parameters.

PMID- 30241079
TI  - Aging effects on the mobility of Pb in soil: Influence on the energy requirements
      in electroremediation.
AB  - This paper studies the possible differences in the behavior of lead as a
      contaminant in soil samples when it is present as "naturally-aged" for decades
      after the contamination, and when it has been spiked in the laboratory. This
      behavior differences are stablished mainly in two ways: as changes in the
      fractionation analysis obtained after a sequential extraction procedure (SEP) and
      as changes in the efficiency of the acid-enhanced electroremediation (EKR)
      technique. Additionally, aging effects have been studied for almost five years.
      In the case of the lead-spiked soil the influence of storage conditions on
      contaminant behavior have also been explored: 1) samples stored in capped
      containers at constant moisture conditions, and 2) samples in containers open to
      the atmosphere, with periods of water flooding and drying. Lab-spiked and the
      "naturally-aged" contaminants show very different behavior with respect not only
      to SEP analysis but also to EKR experiments. The soil spiked with a soluble lead
      salt presents a higher percent in the more mobile fractions. Regarding storage
      conditions, some changes were observed in the lead distribution along the
      vertical soil profile for samples stored in uncapped containers. The EKR results
      were also in agreement with those from fractionation analysis. Energy
      requirements for the remediation were estimated by a mathematical model with
      important differences obtained for the different soil samples. Results are
      indicating that it will be very unreliable to draw estimations for the "naturally
      aged" soils from contaminant-spiked samples.

PMID- 30241080
TI  - Negative impact of the imidazolium-based ionic liquid [C8mim]Br on silver carp
      (Hypophthalmichthys molitrix): Long-term and low-level exposure.
AB  - This study aimed to determine the chronic toxicity of the ionic liquid (IL) 1
      methyl-3-octylimidazolium bromide ([C8mim]Br) on silver carp to further study the
      toxicological mechanism of ILs. For this purpose, 60-d chronic exposure at
      concentrations of 1.09 or 4.38 mg L-1 [C8mim]Br in silver carp was conducted. The
      results of biochemical assays revealed that [C8mim]Br-treatment remarkably
      promoted serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), acid phosphatase (ACP), and alkaline phosphatase
      (AKP) activities, indicating that [C8mim]Br-exposure caused fish organ damage.
      Long-term exposure of [C8mim]Br also altered the activities of superoxide
      dismutase (SOD) and catalase (CAT) and the glutathione (GSH) level but increased
      malondialdehyde (MDA) levels in fish brain, gill, intestine, kidney, liver, and
      muscle, suggesting that [C8mim]Br-treatment may cause oxidative stress in fish
      organs. Further work revealed that [C8mim]Br-treatment increased the activities
      of erythromycin-N-demethylase (ERND) and glutathione S-transferases (GST), which
      may participate in the metabolism of [C8mim]Br in fish liver. Moreover, chronic
      [C8mim]Br-exposure remarkably promoted the expression of inducible nitric oxide
      synthase (iNOS), interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF
      alpha), and nuclear factor-kappaB (NF-kappaB) and altered the levels of
      transforming growth factor-beta (TGF-beta), suggesting that long-term exposure of
      [C8mim]Br might promote the inflammatory response in fish liver. Additionally,
      [C8mim]Br-exposure altered succinate dehydrogenase (SDH) activity and promoted
      caspase-9 and caspase-3 activities in fish liver, suggesting that chronic
      [C8mim]Br-exposure also induces hepatocellular apoptosis via the mitochondrial
      pathway. The results presented here may be helpful to illuminate the chronic
      toxicity mechanism of imidazolium-based ILs and safe use of ILs in the future.

PMID- 30241081
TI  - Carbon and nitrogen stable isotope fractionation during abiotic hydrolysis of
      pesticides.
AB  - Compound-specific Stable Isotope Analysis (CSIA) has been recently established as
      a tool to study pesticide degradation in the environment. Among degradative
      processes, hydrolysis is environmentally relevant as it can be chemically or
      enzymatically mediated. Here, CSIA was used to examine stable carbon and nitrogen
      isotope fractionation during abiotic hydrolysis of legacy or currently used
      pesticides (chloroacetanilide herbicides: Acetochlor, Alachlor, S-Metolachlor and
      Butachlor, acylalanine fungicide: Metalaxyl, and triazine herbicide: Atrazine).
      Degradation products analysis and CN dual-CSIA allowed to infer hydrolytic
      degradation pathways from carbon and nitrogen isotopic fractionation. Carbon
      isotopic fractionation for alkaline hydrolysis revealed similar apparent kinetic
      isotope effects (AKIEC = 1.03-1.07) for the 6 pesticides, which were consistent
      with SN2 type nucleophilic substitutions. Neither enantio-selectivity (EF ~ 0.5)
      nor enantio-specific isotope fractionation occurred during hydrolysis of R (AKIEC
      = 1.04 +/- 0.01) and S (AKIEC = 1.04 +/- 0.02) enantiomers of a racemic mixture
      of Metalaxyl. Dual element isotope plots enabled to tease apart CCl bond breaking
      of alkane (Lambda ~ epsilonN/epsilonC ~ 0, Acetochlor, Butachlor) and aromatic pi
      system (Lambda ~ 0.2, Atrazine) from CO bond breaking by dealkylation (Lambda ~
      0.9, Metalaxyl). Reference values for abiotic versus biotic SN2 reactions derived
      from carbon and nitrogen CSIA may be used to untangle pesticide degradation
      pathways and evaluate in situ degradation during natural and engineered
      remediation.

PMID- 30241082
TI  - Fabrication of slag particle three-dimensional electrode system for methylene
      blue degradation: Characterization, performance and mechanism study.
AB  - In order to solve the problem of slag recycling and dyeing wastewater treatment
      synchronously, the slag particles is used as raw material to prepare the particle
      electrodes, and the optimum preparation conditions of the slag particle
      electrodes is obtained through orthogonal test. Scanning electron microscopy, X
      ray diffractometer and micro-hole physics and chemical adsorption analyzer are
      used to characterize and analyze the surface morphology, crystal structure,
      specific surface area and pore shape of the particle electrode. The operating
      parameters of the reaction system are optimized, and the energy consumption per
      order is calculated in optimized experimental conditions. The radical scavenging
      mechanism of three free radical scavengers (methanol, tert-butanol, and phenol)
      is studied, and the type of the main active substance participating in
      degradation of Methylene blue and the location of the degradation reaction are
      determined. It is speculated that the degradation reaction of Methylene blue
      occurs in the boundary layer on the external surface of the particle electrodes,
      not in the aqueous solution.

PMID- 30241083
TI  - Metabolic responses of Ulva compressa to single and combined heavy metals.
AB  - Accumulation of metals and metabolic responses were studied for two Cd and Cu
      concentrations (1 and 10 MUM) either alone or as a combination in marine
      macroalga after 7 days of exposure. Cd accumulated more at a low dose (115 MUg of
      Cd/g DW) but Cu at a high dose (378 MUg of Cu/g DW); Cu suppressed Cd
      accumulation (by 57%). Na and Zn levels were unaffected, but higher metal doses
      depleted K and Ca levels. Higher metal concentrations strongly stimulated
      reactive oxygen species and depleted nitric oxide (NO) formation, but differences
      between the action of Cd and Cu were not extensive. Higher metal doses increased
      cell wall thickness with a potential relation to NO signal that is visible mainly
      in the apoplast in those treatments. A higher Cu dose depleted proline, ascorbic
      acid, and phenol levels more than Cd, whereas Cd elevated nonprotein thiols and
      ascorbic acid in combined treatments. An eventual role of malic or citric acid in
      metal chelation was not evident: malic acid level decreased in all treatments.
      The total content of fatty acids reached 16.7 mg/g DW in control with the
      quantitative order of PUFAs > SFAs > MUFAs; palmitic, vaccenic, linoleic, and
      alpha-linolenic acids were the major compounds. Cu was more toxic for fatty acids
      than Cd (even at 1 MUM); mainly, PUFA levels strongly decreased (from 43% of
      total acids in control to 28.9% and 5.4% at 1 and 10 MUM Cu treatment,
      respectively). Results are precisely and critically discussed in relation to
      limited literature focused on macroalgae, and a comparison with microalgae is
      also provided.

PMID- 30241084
TI  - Serum organochlorines and non-Hodgkin lymphoma: A case-control study in Israeli
      Jews and Palestinians.
AB  - Associations of organochlorine (OC) pesticides and polychlorinated biphenyls
      (PCBs) with non-Hodgkin lymphoma are controversial. We compared serum levels of 6
      OC pesticides and 38 PCBs in Israeli Jews (IJ) and Palestinian Arabs (PA) and
      assessed possible associations with B-cell non-Hodgkin lymphoma (B-NHL). Ninety B
      NHL cases (50 IJ and 40 PA) and 120 controls (65 IJ and 55 PA) were included.
      Median concentrations of analytes in controls were compared across ethnic groups
      using quantile regression, adjusting for age and sex. We used logistic regression
      to derive odds ratios (OR) and 95% confidence intervals (CI) for detectable
      analytes and B-NHL, adjusting for age, ethnic group, faming and body mass index.
      Median values of PCBs and dichlorodiphenyldichloroethylene (DDE) were higher in
      IJ vs PA controls (P = 0.0007), as were several PCBs (74, 99, 118, 138, 146, 153,
      156, 163, 170, and 180). Overall, OC pesticide and PCB exposures were comparable
      with reports from high-income countries. B-NHL was associated with PCB 146 (OR
      1.70, 95% CI: 1.02, 2.83), PCB 156 (OR 1.75, 95% CI: 1.06, 2.89), and high
      chlorinated PCBs (OR 1.55, 95% CI: 1.00, 2.40) in all study subjects. These
      associations were robust in quantile as well as sensitivity analyses. An
      association of DDE with B-NHL was noted in PA (OR 1.72, 95% CI: 1.07, 2.77), but
      not in IJ (OR 0.87, 95% CI: 0.59, 1.27). Although high-chlorinated PCB
      concentrations did not indicate high exposure levels, our findings indicate that
      B-NHL may be associated with this exposure.

PMID- 30241085
TI  - Corrigendum to "Embodied disruption: "Sorting out" gender and nonconformity in
      the doctor's office" [Soc. Sci. Med. (2018) 352-358].

PMID- 30241086
TI  - "We've all had patients who've died ...": Narratives of emotion and ideals of
      competence among junior doctors.
AB  - Although there is reasonably rich literature on socialisation in medical schools,
      few studies have investigated emotional socialisation among qualified doctors;
      specifically how specialist training reproduces the norms, values, and
      assumptions of medical culture. This article explores expressions and management
      of emotion in doctors' narratives of work and training for insights into how
      socialisation continues after graduation. The study employed qualitative methods 
      in-depth interviews - with fifty doctors at early and advanced stages of
      specialist training in teaching hospitals in Ireland. The study found that
      performance of competence, particularly for doctors at earlier training stages,
      required them to hide signs of struggle and uncertainty. Competence was
      associated with being emotionally tough, which involved hiding emotional
      vulnerability; however, some challenged the assumption that doctors should be
      able to transcend emotionally painful events. Tensions between this expression of
      competence and making time for self-care meant that the latter was often
      neglected. Some participants highlighted how they enjoyed more personal
      interactions with patients, which was juxtaposed with the expectation of being
      detached and an associated potential to objectify patients. This theme resonates
      with recent debates on "appropriate" expressions of empathy and its implications
      for patient-doctor relationships. The article discusses how ideas underpinning
      the image of medical invincibility should be questioned as part of efforts to
      reform medical culture and in the training of specialists in emotional wellbeing
      and self-care.

PMID- 30241087
TI  - A rare case of Brooke-Spiegler syndrome: integrated surgical treatment of
      multiple giant eccrine spiradenomas of the head and neck in a young girl.
AB  - INTRODUCTION: The authors present a "four-step" integrated surgical protocol to
      treat a rare case of multiple giant eccrine spiradenoma (ES) of the head and neck
      in a young patient. PRESENTATION OF CASE: An 18-year-old female patient presented
      with multiple swellings in the head and neck regions. The patient had a severe
      psychological trauma with a negative impact on her social life. Physical
      examination revealed multiple papulo-nodular swellings measuring between 5 cm * 8
      cm and up to 10 cm * 20 cm in size with cerebriform aspect and soft consistency.
      Major lesions were located in the scalp, frontal area, neck, occipitotemporal,
      and retroauricular regions. Tissue biopsy found a benign composite adnexal
      neoplasm consisted in ES, trichoepithelioma, and cylindroma, a typical feature of
      Brooke-Spiegler Syndrome. A staged excision was planned, and available
      reconstructive options were considered. Scalp reconstruction included tissue
      expansions, advancement flaps, skin grafts, and dermal regeneration template
      (Integra(r)). All treatments were successful, and no recurrence was observed. The
      patient returned to a normal social life, and a radical excision with satisfying
      aesthetic results was achieved. DISCUSSION: Although adnexal tumors are benign in
      most of the cases, these lesions are prone to arise in the craniofacial region,
      thereby causing aesthetic discomfort associated with pain, hemorrhage, and
      infection to the patient every day. Furthermore, there is a potential risk of
      malignant transformation. These concerns demonstrate the need to establish a
      surgical protocol for the treatment of adnexal tumors. CONCLUSIONS: Our
      integrated surgical approach showed excellent aesthetic and functional results
      with benefits to the patient's life and complete oncological excision.

PMID- 30241088
TI  - The impact of varying abiotic humification conditions and the resultant
      structural characteristics on the copper complexation ability of synthetic humic
      like acids in aquatic environments.
AB  - Humic acid (HA) has a high complexation ability with metal ions due to its
      functional groups. In this study, 11 synthetic humic-like acids (SHLAs) were
      prepared under varying abiotic humification conditions: precursor species
      (glycine-catechol and glycine-catechol-glucose), precursor concentrations (from
      0.25 M:0.25 M to 1 M:1 M), pH (6-8), temperature (25-45  degrees C) and mass of
      MnO2 catalyst (1.3-2.5% w/v). The effect of the varying humification conditions
      on the complexation ability of the SHLA for Cu2+ were investigated together with
      the relationships between Cu complexation ability and the structure of the SHLAs
      (elemental composition, type and content of functional groups, AL/AR, E4/E6).
      Conditional stability constants (log K) of the SHLAs ranged from 6.00 to 6.42 and
      complexation capacities ranged from 1.76 mmol/g to 2.61 mmol/g. SHLAs synthesized
      at lower temperature (25 C), pH 8, low precursor concentrations
      (glycine:catechol= 0.25 M:0.25 M) and a larger proportion of catalyst (2.5% w/v)
      had a larger copper complexation ability. Log K values of SHLAs had significant
      positive correlations with carboxylic carbon (r = 0.671, p < 0.05), carboxylic
      group content (r = 0.890, p < 0.01) and O/C ratio (r = 0.618, p < 0.05), and
      significant negative correlations with aliphatic carbon (r = -0.616, p < 0.05),
      total C (r = -0.685, p < 0.05) and total H contents (r = -0.654, p < 0.05).
      Complexation capacities had a significant positive correlation with total N (r =
      0.826, p < 0.01) and a significant negative correlation with C/N ratio (r = 
      0.823, p < 0.01).

PMID- 30241089
TI  - Tolerance mechanism of Triarrhena sacchariflora (Maxim.) Nakai. seedlings to lead
      and cadmium: Translocation, subcellular distribution, chemical forms and
      variations in leaf ultrastructure.
AB  - Hydroponic experiments were conducted to assess the accumulation, translocation,
      and chemical forms of lead (Pb) and cadmium (Cd) in the roots, stems, and leaves
      of Triarrhena sacchariflora seedlings and the associated variation in leaf
      ultrastructure. The leaves and leaf ultrastructure showed no significant symptoms
      of toxicity with 0.05 mM Pb or 0.01 mM Cd exposure for 10d. Chlorosis and wilting
      were observed in leaves when the Pb and Cd concentration was higher than 0.1 and
      0.05 mM in the medium, respectively, as demonstrated by severe ultrastructural
      modifications at higher concentration in the leaves, such as plasmolysis, cell
      wall detachment, chloroplast swelling, nuclear condensation, and even nuclear
      fragmentation. The Pb and Cd concentrations in the roots was significantly higher
      than those in the stems and leaves. This indicated low Pb and Cd translocation
      from the roots to the aboveground parts. Subcellular distribution analysis showed
      that the majority of Pb and Cd was bound to the cell wall, especially in the
      roots, indicating that the cell wall likely constitutes a crucial storage site
      for Pb and Cd. This mechanism decreases the translocation of Pb and Cd across
      membranes and is more effective than vacuolar compartmentation. The majority of
      Pb and Cd exited in form of insoluble Pb/Cd-pectate or -oxalate complexes in the
      plant. In conclusion, higher concentrations of Pb or Cd induced premature
      senescence. High Pb and Cd enrichment was observed in the roots, which decreased
      the translocation of Pb and Cd from the roots to the aboveground tissues. The
      immobilization of Pb or Cd by the cell wall is important for plant detoxification
      and can protect protoplasts from Pb or Cd toxicity. Pb and Cd mainly existed in
      insoluble Pb/Cd-phosphate or -oxalate complexes, exhibiting low activity and
      thereby limiting symplastic transport and suppressing toxicity.

PMID- 30241090
TI  - Protective effects of farnesol on a Rhizobium strain exposed to cadmium.
AB  - Soil acts as a repository for many metals that human activity releases into the
      environment. Cadmium enters agricultural soils primarily from application of
      phosphate fertilizers and sewage sludge. Among soil bacteria, rhizobia have a
      great agronomic and environmental significance and are major contributors to a
      sustainable maintenance of soil fertility. However, the services that this group
      of microorganisms provides are affected by environmental constraints, such as Cd
      contamination. Bioactive compounds also influence soil microorganisms. Farnesol
      is a phytocompound with recognized bioactivity, inducing both beneficial and
      harmful effects. In this study, Rhizobium sp. strain E20-8 was exposed to sole or
      combined exposure to Cd and farnesol. Results showed that farnesol (25 and 200
      uM) did not affect rhizobia; exposure to Cd (uM) inhibited rhizobia growth and
      induced several biomarkers of oxidative stress; exposure to the combination of
      farnesol and Cd reduced oxidative damage, and the highest concentration of
      farnesol tested reduced Cd accumulation and allowed a significant growth
      recovery. Farnesol protective effects on rhizobia exposed to Cd is novel
      information which can be used in the development of microbe-based environmental
      engineering strategies for restoration of metal contaminated areas.

PMID- 30241091
TI  - Effects of straw leachates from Cry1C-expressing transgenic rice on the
      development and reproduction of Daphnia magna.
AB  - The transgenic rice line T1C-19 provides high resistance to lepidopteran pests
      because of the synthesis of the Bacillus thuringiensis (Bt) insecticidal protein
      Cry1C. It thus shows good prospect for commercial planting in China. Species of
      Cladocera, an order of aquatic arthropods commonly found in aquatic ecosystems
      such as rice paddies, might be exposed to the insecticidal protein released from
      Bt-transgenic rice-straw residues. For the study reported herein, we used Daphnia
      magna (water flea) as a representative of Cladocera to evaluate whether aquatic
      arthropods are adversely affected when exposed to Bt rice-straw leachates. We
      exposed D. magna to M4 medium containing various volume percentages of medium
      that had been incubated with T1C-19 rice straw or rice straw from its non
      transformed near-isoline Minghui 63 (MH63) for 21 days. Compared with pure M4
      medium (control), the fitness and developmental and reproduction parameters of D.
      magna decreased significantly when exposed to rice-straw leachates; conversely,
      no significant differences between the T1C-19 and MH63 rice-straw leachate
      treatments were observed, indicating that the Bt rice straw leachate did not
      adversely affect this non-target species.

PMID- 30241092
TI  - Comparative studies on growth and Pb(II) removal from aqueous solution by Nostoc
      muscorum and Anabaena variabilis.
AB  - Industrial wastewater containing heavy metals is a major environmental problem
      that needs to be treated. This study reported the ability of two fresh water
      algae cyanobacteria (Nostoc muscorum and Anabaena variabilis) to remove lead from
      aqueous solutions of four different initial concentrations (0-50 mg/L-1) for 21
      days under controlled laboratory conditions. Results obtained in this study
      showed a maximum removal of Pb(II) (97.8%) by N. muscorum at 15 mg/L-1 initial
      metal concentration however the maximum removal by A. variabilis at the same
      concentration was 71.4% after 16 day of incubation. These N. muscorum appeared to
      be more efficient than A. variabilis for removing Pb(II). Algal growth, pigments
      in the algae cells were measured during incubation period. Lower concentrations
      of lead increased biomass, OD, chlorophyll a and carotenoids in both algae. On
      the other hand, higher concentrations of lead were inhibitory for growth.

PMID- 30241093
TI  - Validation of Cameriere's medical-legal age estimation method using seconds
      premolars in a Portuguese population.
AB  - The goal of this project is to validate the Cameriere's method applied to the
      upper and lower second premolars in a Portuguese population, regarding the
      forensic estimate of age. The applied sample consisted in 100 panoramic
      radiographs, of 60 males and 40 females, patients of the Faculty of Dental
      Medicine of the University of Lisbon, whose ages vary between 15 and 35 years
      old. Thus, a total of 400 teeth were investigated (200 upper second premolars and
      200 lower second premolars). Each radiograph was analysed using draw and
      measurement tools featured in Adobe Photoshop, applying the Cameriere's method,
      and then the pulp/tooth ratio was computed for the 15, 25, 35 and 45 teeth. All
      data were statistically analysed with the SPSS program, using a significant level
      of 5%. It was not observed any kind of relation, linear or not linear, between
      age and the pulp/tooth ratio. Linear regressions with considerably low values for
      the coefficient of determination were achieved, which indicates a low reliability
      for these models. Accordingly, we conclude that the knowledge of the pulp/tooth
      ratio does not allow the identification of an individual based on the Cameriere's
      method, in the scope of a forensic age estimate applied to panoramic radiograph.
      Further investigations with larger samples and broader age groups are required in
      order to provide suitable evidence to the legal and social aspects of age
      estimate in Forensic Dentistry.

PMID- 30241094
TI  - Kinematic differences between children with obstetric brachial plexus palsy and
      healthy controls while performing activities of daily living.
AB  - BACKGROUND: Residual shoulder dysfunction and deformity impacts on functional
      performance in children with obstetric brachial plexus palsy. Clinical
      understanding of upper limb dynamic movement patterns is difficult with
      observation alone. This case-control study describes the significant kinematic
      differences between children with obstetric brachial plexus palsy compared to
      typically developing children while performing tasks of the modified Mallet
      Scale. METHODS: Eleven children with obstetric brachial plexus palsy (mean 10
      years, range 7-15 years, Narakas group I-III) and 10 typically developing
      children (mean 9 years 9 months, range 6-15 years) completed three-dimensional
      upper limb motion analysis using the acromion method to track dynamic scapular
      movement. Kinematic data were captured by a 4-CODA cx1 optoelectronic tracking
      system. Participants performed three trials of the modified Mallet scale tasks.
      Local coordinate systems, segment and joint rotations were defined as recommended
      by the International Society of Biomechanics. FINDINGS: Joint rotation angles
      against time of the glenohumeral, thoracohumeral and scapulohumeral joints were
      calculated. Kinematic findings demonstrated increased internal rotation in all
      postures, reduced glenohumeral excursion, habitual "trumpet" posture of
      glenohumeral abduction/elevation and variability in movement strategies.
      Scapulohumeral rhythm during abduction task was 1.88:1 in typically developing
      children and 1.04:1 in children with obstetric brachial plexus palsy.
      INTERPRETATION: Children with obstetric brachial plexus palsy demonstrate
      deficient external rotation in all tasks. Despite increased postural internal
      rotation, ability to move through internal rotation range is compromised. The
      glenohumeral joint showed the greatest range deficit, contributing to abnormal
      scapulohumeral rhythm. Future sub-group analysis of Narakas Classification is
      recommended.

PMID- 30241095
TI  - Poor sleep quality and late-life depression among the elderly in urban
      communities in liaoning, China: A moderated mediation analysis.
AB  - This study aims to investigate a moderated mediation model in the relationship
      between poor sleep quality, depressive symptoms, perceived stress, sense of
      coherence. A cross-sectional survey was conducted from May to July 2015 in
      Liaoning Province, China. 1050 community residents aged >=60 years were
      ultimately chosen to participate. The Chinese version of the Pittsburgh Sleep
      Quality Index (CPSQI), the Epidemiological Studies Depression Scale(CES-D),the
      Chinese version Perceived Stress Scale(CPSS), and the Sense of Coherence Scale
      (SOC) were used to estimate sleep quality, late-life depression, perceived
      stress, and sense of coherence (SOC) respectively. Pearson's correlations and the
      PROCESS macro were applied to analyze the data. The results showed that perceived
      stress partially mediated the association between poor sleep quality and
      depression symptoms (35% proportion mediated). In addition, the effect of poor
      sleep quality and the effect of perceived stress on late-life depression was
      moderated by SOC.The current findings indicates that the impact of poor sleep
      quality on late-life depression through perceived stress can be buffered when the
      elderly individuals have a high SOC. Interventions should therefore target
      individuals who are classified as poor sleepers but only have a lower SOC score.
      However, longitudinal studies should be conducted in future to substantiate these
      findings. Importantly, this research provides a useful theoretical and
      methodological approach for prevention of depression among the elderly in urban
      China.

PMID- 30241097
TI  - [18th Experts Meeting Parkinson in Frankfurt / Main].

PMID- 30241096
TI  - Dynamic signatures: A review of dynamic feature variation and forensic
      methodology.
AB  - This article focuses on dynamic signatures and their features. It provides a
      detailed and critical review of dynamic feature variations and circumstantial
      parameters affecting dynamic signatures. The state of the art summarizes
      available knowledge, meant to assist the forensic practitioner in cases
      presenting extraordinary writing conditions. The studied parameters include
      hardware-related issues, aging and the influence of time, as well as physical and
      mental states of the writer. Some parameters, such as drug and alcohol abuse or
      medication, have very strong effects on handwriting and signature dynamics. Other
      conditions such as the writer's posture and fatigue have been found to affect
      feature variation less severely. The need for further research about the
      influence of these parameters, as well as handwriting dynamics in general is
      highlighted. These factors are relevant to the examiner in the assessment of the
      probative value of the reported features. Additionally, methodology for forensic
      examination of dynamic signatures is discussed. Available methodology and
      procedures are reviewed, while pointing out major technical and methodological
      advances in the field of forensic handwriting examination. The need for sharing
      the best practice manuals, standard operating procedures and methodologies to
      favor further progress is accentuated.

PMID- 30241098
TI  - [Neuropalliative care aspects in patients with Parkinson's disease].
AB  - Palliative Care in Parkinson's Disease (PD) is of growing interest. The burden of
      symptoms of late-stage PD patients is similar or even higher than those of
      patients suffering from oncological diseases. However, patients suffering from
      advanced phases of PD have tremendous unmet palliative care needs. The disease
      trajectories are often difficult to define, and initiation of palliative care
      approach has to be chosen carefully. Swallowing difficulties define the onset of
      the late and palliative phase and have to be seen as a landmark for palliative
      care involvement. Here we provide an approach to palliative care in PD in the
      final phase and also care for the relatives.

PMID- 30241099
TI  - [Nutritional aspects in Parkinson's disease: disease risk, dietary therapy and
      treatment of digestive tract dysfunction].
AB  - Epidemiological studies suggest an association of certain foods with the risk of
      Parkinson's disease. Also, a number of studies revaeled positive effects on
      disease progression by caffeine, higher uric acid and total cholesterol levels -
      especially in men. However, it is not yet clear whether a specific dietary
      concept or the effects of the intestinal microbiota on the human metabolism could
      play a role in the course of the disease. Given the lack of prospective nutrition
      studies, only general recommendations can be given: a "balanced" seasonal
      regional diet with emphasis on vegetables, fruits, nuts, fish, low amount of red
      meat, and non-processed foods with a low level of simple carbohydrates may be
      helpful. Especially for the elderly, a low-protein diet should be avoided.
      Rather, in order to prevent the development of sarcopenia and malnutrition,
      particular attention must be paid to adequate protein intake. The supply of
      vitamins B12 and D3 must be ensured - at the same time, the non-critical use of
      dietary supplements, especially micronutrients with presumed anti-oxidative
      properties, should be discouraged.

PMID- 30241100
TI  - [Dementia with Lewy bodies].
AB  - Dementia with Lewy bodies is characterized histopathologically by the deposition
      of alpha-synuclein in inclusion bodies. Clinical diagnosis is based on
      progressive cognitive deficits, cognitive fluctuations, early visual
      hallucinations, REM sleep disorders and symptoms of Parkinsonism. On the basis of
      the new criteria published in 2017, better differentiation from other
      neurodegenerative diseases with dementia should be possible. Therapy concepts
      include treatment of loss of motor and cognitive performance as well as
      psychological and behavioral symptoms. At present, only a few studies are
      available on this clinical picture so that evidence-based therapy approaches are
      only possible to a limited extent.

PMID- 30241101
TI  - ?

PMID- 30241102
TI  - Ahead of the Curve: Tracking Progress in Novice Microsurgeons.
AB  - BACKGROUND:  The purpose of this study was to evaluate learning curves for an
      existing microsurgical training model. We compared efficiency and amount of
      training needed to achieve proficiency between novice microsurgeons without
      operative experience versus those who had completed a surgical internship.
      METHODS:  Ten novice microsurgeons anastomosed a silastic tube model. Time to
      perform each anastomosis, luminal diameter, and number of errors were recorded.
      RESULTS:  First year residents improved up to a brief plateau at 10 repetitions,
      followed by continued improvement. Second year residents improved up to a plateau
      at 10 repetitions with no further improvement thereafter. There was no
      significant difference in luminal area or errors between groups. CONCLUSION: 
      Residents with no operative experience can benefit from early exposure to
      microsurgical training. These interns continue to improve with additional
      repetitions while second year residents achieve proficiency with fewer
      repetitions.

PMID- 30241103
TI  - Long-Term Effects on Volume Change in Musculocutaneous Flaps after Head and Neck
      Reconstruction.
AB  - OBJECTIVE:  Musculocutaneous flap reconstruction surgery is one of the standard
      procedures following head and neck cancer resection. However, no previous studies
      have classified flaps in terms of muscle and fat or examined them after long-term
      follow-up. The purpose of this study was to estimate the fat and muscle volume
      changes in musculocutaneous flaps during long-term follow-up. METHODS:  We
      conducted a retrospective analysis of 35 patients after musculocutaneous flap
      reconstruction. The total, fat, and muscle volumes of the musculocutaneous flaps
      were measured using 3-dimensional images. Changes in flap volumes over time (1
      month, 1 year [POY1], and 5 years [POY5] postoperatively) were assessed. Flap
      persistence was calculated using flap volumes at 1 month after reconstruction for
      reference. RESULTS:  Flap persistence at POY5 was 42.0% in total, 64.1% in fat,
      and 25.4% in muscle. Muscle persistence was significantly decreased (p < 0.0001).
      In a multiple regression analysis, decreased body mass index (BMI) of >= 5%
      influenced fat persistence less than muscle persistence at POY1; however, there
      was no significant difference at POY5. Postoperative radiation therapy was
      associated with a significant decrease in total flap persistence at POY1 (p =
      0.046) and POY5 (p = 0.0097). Muscle persistence significantly decreased at POY5
      (p = 0.0108). Age significantly influenced muscle volume at POY1 (p = 0.0072).
      CONCLUSION:  Reconstruction flaps are well-preserved with high fat-to-muscle
      ratios. Recommendations for weight maintenance are necessary for patients less
      than 2 years after surgery due to the influence of BMI on fat persistence.
      Radiation therapy is necessary for some patients based on their disease state.
      Intensity-modulated radiation therapy can be offered to reduce scattering
      irradiation to normal tissues.

PMID- 30241104
TI  - Arterial Stiffening with Ultrafast Ultrasound Imaging Gives New Insight into
      Arterial Phenotype of Vascular Ehlers-Danlos Mouse Models.
AB  - OBJECTIVE:  Vascular Ehlers-Danlos syndrome (vEDS) is associated with arterial
      ruptures due to a mutant gene encoding collagen type III (Col-III). To better
      understand the role of Col-III, we aimed at evaluating aortic stiffness and
      dynamic stiffening in vEDS mouse models, with either a quantitative (col3KO mice)
      or a qualitative Col-III defect (col3KI mice). MATERIALS AND METHODS:  Abdominal
      aortic wall pulse wave velocities (PWV) in col3KO and col3KI mice were compared
      to their respective wild type (WT) littermates using a 15 MHz ultrafast
      ultrasonic transducer. A carotid catheter continuously monitored pressure changes
      due to phenylephrine injections. PWV1, generated at diastolic blood pressure
      (DBP), and PWV2, at systolic blood pressure (SBP) were recorded. Difference
      between PWV2 and PWV1 (Delta-PWV) normalized by the pulse pressure (PP),
      corresponding to the aortic stiffening over the cardiac cycle, were compared
      between mutant and WT mice, as well as the regression slope of PWV as a function
      of pressure. RESULTS:  Delta-PWV/PP was lower in col3KO (p = 0.033) and col3KI
      mice (p < 0.001) vs. WT-mice regardless of the pressure level. The slope of PWV1
      with DBP increase showed a lower arterial stiffness in mutant mice vs. controls
      in both models. This difference was amplified when evaluating stiffness at
      systolic blood pressure levels with PWV2. CONCLUSION:  In both vEDS mouse models,
      aortic stiffening was reduced, mainly driven by a lower stiffness at systolic
      blood pressure. Defective Col-III may be responsible for this, as it is utilized
      when pressure rises. These pre-clinical data could explain vascular fragility
      observed in vEDS patients.

PMID- 30241105
TI  - The Value of Detailed First-Trimester Ultrasound Anomaly Scan for the Detection
      of Chromosomal Abnormalities.
AB  - PURPOSE:  To evaluate the performance of first-trimester ultrasound screening
      involving a detailed anomaly scan for the detection of trisomy 18, trisomy 13,
      triploidy, Turner syndrome and trisomy 21. METHODS:  Data of pregnant women who
      underwent aneuploidy screening at 11 - 13 weeks of gestation was retrospectively
      analyzed. Crown-rump length (CRL), fetal nuchal translucency thickness (NT) and
      nasal bone (NB) anatomy, blood flow across the tricuspid valve (TV) and through
      the ductus venosus (DV) were assessed. Furthermore, a detailed scan for fetal
      anatomical anomalies (FA) was carried out. Performance of these markers was
      assessed by logistic regression and ROC analyses for different screening models.
      RESULTS:  4005 fetuses were analyzed. 3856 were euploid, 149 aneuploid (trisomy
      18: 40; trisomy 13: 14; triploidy: 3; Turner syndrome: 17; trisomy 21: 75 cases).
      70 - 100 % of the fetuses with trisomy 18 and 13, triploidy and Turner syndrome
      but only 34.7 % with trisomy 21 had at least one fetal defect. Considering all
      aneuploidies, the detection rate (DR) for screening based on MA+NT+NB+TV+DV was
      90.6 % and improved to 96.0 % if an FA was added (fixed false-positive rate: 3
      %). If screening was based on MA+NT+FA, the detection rate for all aneuploidies
      was 85.2 %. However, the DR for trisomy 18, trisomy 13, triploidy and Turner
      syndrome (excluding trisomy 21) was 94.6 %, indicating the high diagnostic value
      of an anomaly scan for these aneuploidies. CONCLUSION:  Incorporation of a
      detailed fetal anomaly scan (FA) into first-trimester screening algorithms can
      improve the detection rates for trisomy 18 and 13, triploidy and Turner syndrome.

PMID- 30241106
TI  - Correction: Higher HbA1c Measurement Quality Standards are Needed for Follow-Up
      and Diagnosis: Experience and Analyses from Germany.

PMID- 30241107
TI  - Reasons for Use of and Experiences with Homeopathic Treatment as an Adjunct to
      Usual Cancer Care: Results of a Small Qualitative Study.
AB  - BACKGROUND:  A significant proportion of patients with cancer consult with
      homeopaths. No former qualitative study has reported on experiences with
      homeopathy in this patient group. This study aimed to learn about the reasons
      for, and experiences with, treatment provided by homeopaths among Danish patients
      with cancer. METHODS:  A small qualitative semi-structured interview study was
      carried out to collect preliminary knowledge to learn about reasons for and
      experiences with treatment provided by homeopaths as an adjunct to usual care
      among patients with cancer. Thematic analysis was used for the development of
      themes. RESULTS:  Five patients, diagnosed with cancer, were interviewed. On the
      basis of qualitative interviews five themes emerged: concerns and hopes,
      obstacles and support, internal health locus of control, whole person approach,
      and improved well-being. CONCLUSION:  The cancer patients in this study sought
      homeopathy to address their hopes and concerns and to help them face obstacles
      and find support. They were actively taking responsibility for their own health
      and valued the whole person approach used by their homeopaths. Participants
      reported improved well-being both at the physical and mental levels. The results
      provide a basis for further research to learn more from patients' experiences
      with this intervention. Such knowledge could potentially be helpful to improve
      healthcare practitioners' communication with patients, and thereby patients'
      overall care.

PMID- 30241108
TI  - Effects of Peer Support Interventions on the Communication of Preschoolers with
      Autism Spectrum Disorder: A Systematic Review.
AB  - Many young children with autism spectrum disorders (ASDs) experience difficulty
      in the development of communication skills. Teaching peers to make use of
      communication support behaviors has been investigated as a strategy to increase
      communication for young children with ASD in early childhood settings. The
      purpose of this systematic review was to examine (1) the overall effects of peer
      support interventions on the communication of young children with ASD and (2) any
      possible moderating variables related to participant and intervention
      characteristics. The social support model was used as a framework for the study
      of intervention components. Eighteen single-case experimental design studies (48
      children with ASD) met the inclusion criteria and were advanced to the full
      coding and analysis phase of the investigation. Descriptive analyses and effect
      size estimations using the improvement rate difference (IRD) metric were
      conducted. Overall, peer support interventions were found to be effective across
      a range of young children with ASD and intervention approaches. Evidence was also
      identified for the use of the social support model as a framework to guide the
      development of peer interventions in early childhood settings. The use of
      friendship groups, the selection of play materials based on the interests of the
      child with ASD, and the provision of augmentative and alternative communication
      appeared to be associated with positive communication outcomes.

PMID- 30241109
TI  - European Academy of Cancer Sciences - position paper.
AB  - The European Academy of Cancer Sciences (EACS) is an independent advisory body of
      well-recognised medical specialists and researchers striving to create a
      compelling interactive continuum of cancer research, from innovative basic
      research to implementation of state-of-the-art evidence-based cancer care and
      prevention. Achieving the above will entail bridging high-quality basic and
      preclinical cancer research to research on prevention, early detection and
      therapeutics as well as improving coordination of translational research efforts
      across Europe. The latter is expected to be expedited through quality assuring
      translational cancer research in Comprehensive Cancer Centres - entities that
      link research with the healthcare system - and networks of cancer research
      centres. Achieving a critical mass of expertise, resources and patients is
      crucial. Improving late translational research, which involves clinical studies
      to assess effectiveness, and added value for the health care is also a high
      priority. Both high-quality Big Data collections and the intelligent use of these
      data will promote innovation in cancer research and support outcomes research to
      assess clinical utility, quality of cancer care and long-term follow-up of
      treated patients. The EACS supports the mission-oriented approach recently
      proposed by the European Commission in Horizon Europe to deal with major
      challenges and would like to persuade the EU and its member states to formally
      launch a mission in cancer to boost and streamline the cancer research continuum
      in Europe. Building a coherent translational cancer research continuum with a
      focus on patients and individuals at risk will require, however, foresight as
      well as the extensive and continuous provision of evidence-based advice to inform
      policy.

PMID- 30241111
TI  - The good, the bad, but not the ugly.

PMID- 30241112
TI  - Metabolic rates and the energetic cost of external tag attachment in juvenile
      blacktip sharks Carcharhinus limbatus.
AB  - This study reports on the metabolic rate of the blacktip shark Carcharhinus
      limbatus and the energetic costs of external tag attachment. Metabolic rates,
      swimming speed and tail-beat (BT ) frequency were measured in a static
      respirometer with untagged animals and animals equipped with a small data logger.
      Tagged sharks showed significantly higher routine oxygen consumption and lower
      swimming speeds than untagged animals, indicating that tagging significantly
      affected the swimming efficiency and energetic requirements in these small
      sharks, and that these effects must be accounted for when interpreting telemetry
      data from free-ranging individuals.

PMID- 30241110
TI  - The vertical distributions and spawning site choices of red and yellow bluefin
      killifish Lucania goodei colour morphs.
AB  - A genetic colour polymorphism is present in bluefin killifish Lucania goodei,
      where red and yellow anal-fin morphs coexist in clear springs, but the source of
      balancing selection is unknown. In a field study, vertical distributions did not
      differ between the morphs and there was little evidence that light environments
      differed qualitatively over the 200 cm at which fish were collected. A greenhouse
      study showed that both morphs preferred to spawn at shallow depths and hence
      vertical distribution and spawning site choice are unlikely to explain the
      maintenance of the colour polymorphism.

PMID- 30241113
TI  - Is resource partitioning the key? The role of intra-interspecific variation in
      coexistence among five small endemic fish species (Characidae) in subtropical
      rivers.
AB  - This study focused on intra and interspecific variations in the diet of small
      species in the Pelotas River, upper Uruguay River ecoregion. We tested the
      hypothesis that five small characids coexist via resource partitioning. Samplings
      were performed quarterly between August 2013 and May 2014 at 14 sites in the
      Pelotas River basin, using gillnets of different mesh sizes, seines, cast nets
      and electrofishing. In this study, the contents of 1,253 stomachs were analysed
      from Astyanax dissensus, A. paris, A. saguazu, A. xiru and Bryconamericus
      patriciae. The main food resources consumed were aquatic insects, leaves, seeds
      and detritus. There were significant seasonal intra and interspecific variations
      in the use of food resources by the five species. Permutational analysis of
      multivariate dispersions results indicated significant differences in individual
      intraspecific variability between the sampled periods, with the highest values
      found in November and February because of an increase in allochthonous resources
      (leaves and seeds). Besides this, significant differences in the proportions of
      consumption of allochthonous and autochthonous were observed. The trophic niche
      breadth was significantly different among the species, such that in August, the
      species had narrower niche breadths. In the other periods, the highest niche
      breadth values were due to an increase in the consumption of allochthonous items.
      Diet overlap was low (< 0.4) between 62% of the species pairs. The small characid
      species showed pronounced changes in resource use and intra and interspecific
      variations indicating resource partitioning. These factors appear to be essential
      in species interactions and for coexistence.

PMID- 30241114
TI  - Personalizing obesity assessment and care planning in primary care: patient
      experience and outcomes in everyday life and health.
AB  - Obesity is a complex, chronic disease, frequently associated with multiple
      comorbidities. Its management is hampered by a lack of translation of evidence on
      chronicity and pathophysiology into clinical practice. Also, it is not well
      understood how to support effective provider-patient communication that
      adequately addresses patients' personal root causes and barriers and helps them
      feel capable to take action for their health. This study examined interpersonal
      processes during clinical consultations, their impacts, and outcomes with the aim
      to develop an approach to personalized obesity assessment and care planning. We
      used a qualitative, explorative design with 20 participants with obesity,
      sampling for maximum variation, to examine video-recorded consultations, patient
      interviews at three time points, provider interviews and patient journals.
      Analysis was grounded in a dialogic interactional perspective and found eight key
      processes that supported patients in making changes to improve health: compassion
      and listening; making sense of root causes and contextual factors in the
      patient's story; recognizing strengths; reframing misconceptions about obesity;
      focusing on whole-person health; action planning; fostering reflection and
      experimenting. Patient outcomes include activation, improved physical and
      psychological health. The proposed approach fosters emphatic care relationships
      and sensible care plans that support patients in making manageable changes to
      improve health.

PMID- 30241115
TI  - Weight-based victimization from friends and family: implications for how
      adolescents cope with weight stigma.
AB  - BACKGROUND: Youth with overweight and obesity commonly experience weight-based
      victimization. The ways that these youth cope with victimization can adversely
      impact their health. Despite considerable evidence that family members and
      friends are common perpetrators of weight-based victimization, the relationships
      among different sources of victimization and coping responses of youth are
      unknown. OBJECTIVES: The present study examined the relationships between weight
      based victimization from four sources (friends, peers, family members and
      teachers) and stigma-specific coping responses in adolescents using linear
      regression. METHODS: Adolescents (ages 13-18 years; N = 148) enrolled in a
      national weight loss camp completed questionnaires about demographics, weight
      bullying, sources of teasing and internalized weight bias. RESULTS: Teasing
      sources explained a large proportion of the variance in coping strategies for
      weight-based victimization. Weight teasing from friends was associated with
      greater frequency of negative emotions. Weight teasing from peers and friends
      were associated with greater frequency of coping via avoidance behaviours, while
      teasing from family was associated with fewer avoidance behaviours. Adolescents
      reported wanting more support from parents and stronger school policies to
      address weight-bullying. CONCLUSIONS: These results suggest associations between
      weight-teasing sources and coping mechanisms. Interventions should examine the
      role of coping strategies to protect against adverse health effects of weight
      based victimization.

PMID- 30241116
TI  - Injection of SVF combined with HBO2 improves viability of unfavorably designed
      flaps.
AB  - Purpose: Soft-tissue reconstruction is complicated by ischemia and reperfusion
      injury. Animal trials have documented the independent healing benefits of
      hyperbaric oxygen preconditioning (HBOP) and stem cell delivery in cutaneous
      flaps. We explored the role of HBOP and stem cell delivery in flap
      preconditioning and survival. Methods: We designed a randomized controlled trial
      to assess the effects of hyperbaric oxygen preconditioning and stromal vascular
      fraction (SVF) delivery on flap survival. Of the first 24 guinea pigs, six
      received neither HBOP nor injections, and six underwent HBOP without injections.
      Of the remaining 12 animals, six received SVF or saline injections in the absence
      of HBOP. The final six animals received autologous SVF injections or saline
      injections followed by four HBOP treatments. To enhance clinical relevance, a
      group of 6 animals underwent HBOP prior to SVF or saline injections. Thereafter,
      an unfavorably designed cutaneous flap was elevated and assessed via study
      blinded observer, as well as by quantification of TUNEL-positive cells. Results:
      Distal necrosis of the tissue flap was more extensive in the no-intervention
      group (45% of flap). Flaps treated with HBOP only and those treated with SVF
      injections demonstrated only 38.2% and 27.1% distal necrosis. The most
      significant difference occurred in the combination HBOP and SVF group, where
      distal necrosis was only 21.1% of the flap (p <= 0.05). SVF delivery immediately
      prior to flap elevation further minimized distal necrosis of the flap to 15.6%.
      These findings were mirrored by the TUNEL assay. Conclusions: Combining HBOP and
      SVF improves flap viability.

PMID- 30241117
TI  - Use of in-chamber transcutaneous oxygen measurement to determine optimal
      treatment pressure in patients undergoing hyperbaric oxygen therapy.
AB  - Introduction: Hyperbaric oxygen (HBO2) therapy is used to promote healing in
      select problem wounds. Transcutaneous oxygen measurement (TCOM) can be used to
      predict the response of these wounds to HBO2, with in-chamber TCOM values shown
      to be the most predictive. We evaluated the use of in-chamber TCOM values to
      determine optimal treatment pressure. Methods: A retrospective review was
      completed of patients undergoing HBO2 therapy for a lower-extremity wound and who
      had in-chamber TCOM. Data collected included TCOM values, treatment profile, and
      patient outcome. Results: A total of 142 patients were identified. The overall
      results demonstrated healing in 59%, minor amputation (below ankle) in 11.3%, and
      major amputation (above ankle) in 16.2% of patients. 79.3% of patients at 2
      atmospheres absolute (ATA) and 86.6% of patients at 2.4 ATA had transcutaneous
      oxygen pressure (TcPO2) values >=250 mmHg. Among those with TcPO2 ?250 mmHg at 2
      ATA, 41% attained TcPO2 ?250 mmHg at 2.4 ATA. Among those treated at 2 ATA the
      healing rate was 70.6% if TcPO2 ?250 mmHg, and 11.8% if TcPO2 ?250 mmHg
      (P?0.001). Among those treated at 2.4 ATA the healing rate was 33.3% if TcPO2
      ?250 mmHg and 14.3% if TcPO2 ?250 mmHg (P?0.001). Discussion: Determining optimal
      therapeutic pressure for patients undergoing HBO2 is important to maximize
      benefit and minimize risk. This study indicates that in-chamber TCOM can be used
      to select an individualized optimal treatment pressure in patients undergoing
      HBO2 for lower-extremity wounds, including diabetic foot ulcers. This may result
      in better utilization of HBO2 and better outcomes.

PMID- 30241118
TI  - Short-term effects on ocular variables immediately after hyperbaric oxygen
      exposures.
AB  - Purpose: To determine ocular refraction, corneal thickness, corneal radius,
      corneal power, corneal astigmatism and intraocular pressure in patients before
      and immediately after repeated hyperbaric oxygen (HBO2) exposures twice a week
      during six weeks of HBO2 therapy. Methods: 23 patients received HBO2 therapy at
      2.4 ATA for 90 minutes daily in monoplace chambers for six weeks, five days a
      week. The Topcon TRK-1P instrument was installed next to the hyperbaric chambers
      to record the ocular measurements. Results: A gross myopic shift developed at 
      0.95 +/- 0.54 D (P ? 0.001) in the right eye and -0.95 +/- 0.53 D (P ? 0.001) in
      the left eye during the six weeks of treatment. Myopic shift reversion, corneal
      thinning and reduced intraocular pressure appeared as immediate effects after a
      single HBO2 exposure, but resolved before the patients attended for the next
      measurement visit. Conclusions: Ocular variables were influenced by both
      cumulative and transient short-term effects during the HBO2 therapy. The short
      term effects showed that the point of time for performing the ocular measurements
      after HBO2 exposure might influence the result and must be considered before
      making relevant comparisons among studies.

PMID- 30241119
TI  - Evaluation of hyperbaric oxygen effects on slow coronary flow patients using
      gated myocardial perfusion imaging tomography.
AB  - Hyperbaric oxygen (HBO2) is widely used in clinical settings for many disease
      treatments. To investigate the potential effects of hyperbaric oxygen on patients
      with slow coronary flow (SCF) we retrospectively analyzed 98 patients who were
      diagnosed with SCF by coronary artery angiography. Of these, 50 patients received
      conventional treatment only (control group; the other 48 patients received
      hyperbaric oxygen treatment for four weeks in addition to the routine therapy
      (HBO2 group). By using gated myocardial perfusion tomography examination before
      and after treatment, we observed that 71 out of 148 (47.9%) subsegments of
      injured myocardium improved in the control group, while 108 out of 151 (71.5%)
      subsegments of injured myocardium improved in the HBO2 group (P ? 0.05).
      Furthermore, the peak filling rate (PFR), time of peak filling rate (TPFR) and
      mean filling rate during the first one-third of the filling time (MFR/3) were all
      significantly improved in HBO2-treated patients compared to those who received
      conventional treatment only. However, we did not detect any significant effects
      of only treatment on left ventricular end diastolic volume (LVEDV), left
      ventricular end systolic volume (LVESV), nor on left ventricular ejection
      fraction (LVEF). Our results indicate that hyperbaric oxygen therapy can be a
      beneficial and effective medication to improve myocardial perfusion and left
      ventricular diastolic function in SCF patients.

PMID- 30241120
TI  - Effect of adjuvant hyperbaric oxygen on healing of cartilage lesions treated with
      microfracture: an experimental study in rats.
AB  - Purpose: The purpose of this experimental study was to investigate the effect of
      hyperbaric oxygen (HBO2) therapy combined with microfracture technique in the
      treatment of cartilage lesions. Methods: Adult Wistar rats (n=44) were divided
      into six groups. In Groups A, B, C and D, ICRS* (* International Cartilage Repair
      Society) grade 4 cartilage lesions were made on the femoral sulcus of both knees.
      Lesions were microfractured on the left knees; the right knees had no further
      procedure. Groups E and F had no surgery. Groups A, C and E received HBO2 therapy
      once a day, six days a week postoperatively. Groups B, D and F had no HBO2
      therapy. The animals in Groups A, B, E and F were sacrificed after two weeks;
      Groups C and D were sacrificed after four weeks. Semiquantitative scale -
      including filling of defect (microfracture hole), reparative tissue thickness,
      cell morphology and subchondral bone maturation - was used for evaluation. The
      Mann-Whitney test was used to compare individual and total scores. Results: Total
      scores of the two-week group with adjuvant HBO2 therapy were significantly higher
      (P=0.0007) than the two-week standard treatment group. Except for subchondral
      bone maturation, individual scores were significantly higher in the two-week
      group with adjuvant HBO2 therapy. Total scores of the four-week groups were
      similar. Among individual scores of the four-week groups, filling of the defect
      (microfracture hole), and subchondral bone maturation were significantly higher
      (P=0.01, P=0.03) in groups with adjuvant HBO2 therapy. Conclusions: Adjuvant HBO2
      therapy accelerates the healing process of cartilage lesions treated with
      microfracture in rats.

PMID- 30241121
TI  - Effect of hyperbaric oxygen treatment in central retinal artery occlusion.
AB  - Background: Central retinal artery occlusion (CRAO) is a rare and serious
      ophthalmologic emergency with a bad prognosis. Hyperbaric oxygen (HBO2) treatment
      has been reported to improve visual acuity of CRAO patients. However, there are
      unknown variables for HBO2 treatment such as initiation period, number of
      sessions and efficacy. In this study, we aimed to investigate efficacy of HBO2
      treatment in CRAO patients. Methods: Patients who had been diagnosed with CRAO
      and referred to our Hyperbaric Oxygen Treatment Unit with the indication of HBO2
      treatment were included in the study. Patient demographics, their systemic
      diseases, best-corrected visual acuity (BCVA) and the time of visual loss were
      recorded. Oral acetazolamide and topical beta blocker treatments as well as HBO2
      treatments were administered to patients as soon as possible. Patients received
      20 treatments as standard. Visual acuity was examined and recorded following each
      HBO2 treatment administration. Results: 10 eyes (five right, five left) of 10
      patients) were included in the study. While average visual acuity was LogMAR 3
      before the treatment, it was measured as LogMAR 1.8 on average after treatment (P
      ? 0.05). None of the patients were observed to have neovascular glaucoma.
      Conclusions: HBO2 treatment is an efficacious method with few side effects and
      can be used in the treatment of CRAO patients. During acute and subacute periods
      a certain number of HBO2 treatment sessions may be beneficial. Stopping
      treatments before eight completed HBO2 sessions for a patient who did not show
      improvement until that time may miss a patient who would have benefited from HBO2
      treatment.

PMID- 30241122
TI  - Oxygen exposures at NASA's Neutral Buoyancy Lab: a 20-year experience.
AB  - Astronauts training for extravehicular activity (EVA) operations can spend many
      hours submerged underwater in a pressurized suit, called an extravehicular
      mobility unit (EMU), exposed to pressures exceeding 2 atmospheres absolute (ATA).
      To minimize the risk of decompression sickness (DCS) a 46% nitrox mixture is
      used. This limits the nitrogen partial pressure, decreasing the risk of DCS. The
      trade-off with using a 46% nitrox mixture is the increased potential for oxygen
      toxicity, which can lead to severe neurologic symptoms including seizures. Suited
      runs, which typically expose astronauts of 0.9-1.1 ATA for longer than six hours,
      routinely exceed the recommendation for central nervous system oxygen toxicity
      limits (CNSOTL) published by the National Oceanic and Atmospheric Administration
      (NOAA). Fortunately, in over 50,000 hours of suited training dives spanning 20
      years of EVA training operations at NASA's Neutral Buoyancy Laboratory (NBL)
      there has never been an occurrence of oxygen toxicity. This lends support to
      anecdotal sentiment among certain members of the hyperbaric community that the
      NOAA CNSOTL recommendations might be overly conservative, at least for the oxygen
      pressure and time regime in which NBL operates. The NOAA CNSOTL recommendations
      are the result of expert consensus with a focus on safety and do not necessarily
      reflect rigorous experimental evidence. The data from the NBL suited dive
      operations provide a foundation of evidence that can help inform the expert
      discussion on dive-related neurologic oxygen toxicity performance and overnight
      recovery in young, healthy males.

PMID- 30241124
TI  - Body mass index in association with decompression sickness events: cross
      sectional study among small-scale fishermen-divers in southeast Mexico.
AB  - Introduction: Decompression sickness is endemic to small-scale fishermen-divers
      from coastal communities in southeast Mexico; overweight and obesity are also
      highly prevalent in the region. Existing literature suggests it is possible that
      fat tissue could play a role in decompression sickness pathophysiology. Our aim
      in this study is to describe the association between the number and severity of
      DCS events treated at the hyperbaric program and fishermen-diver body mass index.
      Methods: In this cross-sectional study, we obtained anthropometric measurements
      of 105 fishermen-divers and reviewed clinical records of each participant at a
      hyperbaric program. Results: Average BMI among participants was 34.5 +/- 4.7,
      while 9.5% (n=10) were healthy-weighted, 28.6% (n=30) were overweight and 42.8%
      (n=65) were obese. Number of DCS events per diver was associated with BMI and
      severity of DCS in linear regression models. Conclusions: Overweight and obesity
      are highly preventable health problems; our results suggest that an association
      between these conditions and the frequency and the severity of DCS are an
      important topic to be further considered in longitudinal prospective studies.

PMID- 30241123
TI  - Tympanometric evaluation of Eustachian tube function in Polish scuba divers.
AB  - Background: Scuba divers are subjected to relatively high ambient pressures while
      descending. Equalizing maneuvers (e.g., Valsalva) are necessary to open the
      Eustachian tube (ET) and allow air into the middle ear (ME) cavity. Insufficient
      opening of the ET leads to ME barotrauma, which is the most common injury related
      to scuba diving. The study aims were to assess the incidence of ME barotrauma and
      to compare tympanometric parameters and stapedial reflexes in scuba divers and
      non-diving individuals.  Material and methods:: 60 scuba divers participated in
      the study; control consisted of 90 non-diving volunteers without a history of
      otolaryngologic problems. All participants were examined with the use of otoscopy
      and tympanometry with evaluation of ipsilateral stapedial reflexes. The group
      studied was surveyed regarding occurrence of ME barotrauma and diving competence.
      Results: 51.7% of the divers experienced ME barotrauma, the most common symptoms
      being earache and hearing loss. Comparison of the group studied and control
      revealed significantly lower ME pressure and compliance in scuba divers. In scuba
      divers with ME barotrauma, longer time from injury correlates directly with
      greater ME pressure and compliance, indicating tissue recovery. At 4,000Hz 100dB
      percentage of present stapedial reflexes among scuba divers was significantly
      lower than in controls; moreover, a greater number of dives correlated inversely
      with percentage of present stapedial reflexes at 4000Hz 100dB. The reduced
      thresholds at high intensities suggest a negative effect of scuba diving on
      hearing. Conclusions: ME pressure and compliance, however still within the norm,
      are significantly lower in scuba divers than in non-diving healthy volunteers.
      This may be attributed to a subclinical form of barotrauma.

PMID- 30241125
TI  - Severe unintentional first trimester carbon monoxide poisoning: case report.
AB  - Background: The fetus is uniquely susceptible to carbon monoxide (CO) exposure.
      We present a case of severe unintentional CO poisoning in the first trimester of
      pregnancy. Case: A 23-year-old G5P2022 female at 11 weeks' gestational age sat in
      a car with the engine idling. She was unaware that the vehicle's exhaust pipe was
      blocked with snow. She was found to be unresponsive, with an initial
      carboxyhemoglobin (COHb) concentration of 47.1%. She underwent emergent treatment
      with hyperbaric oxygen therapy. The remainder of her pregnancy was complicated by
      a diagnosis of myasthenia gravis. She delivered a full-term infant who was noted
      to have persistently small head circumference. Discussion: Fetal hemoglobin binds
      to CO more tightly than adult hemoglobin, and fetal carboxyhemoglobin
      concentrations are reported to exceed maternal levels. Fetal abnormalities may
      occur after CO poisoning in pregnancy and vary based on the gestational age of
      the fetus at the time of the exposure as well the chronicity of the exposure.
      Conclusion: Fetal survival after maternal CO exposure is possible even with
      significantly elevated maternal COHb concentrations, although teratogenic effects
      may occur depending on the timing of exposure.

PMID- 30241126
TI  - Use of hyperbaric oxygen therapy in quinine-associated visual disturbances.
AB  - Introduction: Hyperbaric oxygen (HBO2 ) therapy is infrequently reported as a
      treatment for poison-induced retinal damage. We describe a case in which HBO2
      therapy was used to treat suspected retinal toxicity induced by quinine. Case
      report: We present a case in which HBO2 was used to treat visual disturbances
      thought to be caused by quinine-induced retinal damage. The patient intentionally
      ingested undisclosed amounts of citalopram and quinine. Following a complicated
      hospital course, including profound shock requiring treatment with four
      vasopressors and a peripheral left-ventricular assist device, the patient, once
      extubated, reported visual abnormalities consistent with those described from
      quinine-induced retinal toxicity. Visual disturbances seemed to show improvement
      following HBO2 treatment. Several months following hospitalization visual defects
      continued to be present on examination. However, with corrective lenses the
      patient's visual acuity was normal. No adverse events were attributed to the use
      of HBO2. Discussion: HBO2 for treatment of quinine-induced retinal damage is
      infrequently reported or studied. In the reported case, use of HBO2 appeared to
      be associated with substantial improvement in visual disturbances occurring in
      the setting of an overdose of quinine. The patient's improvement is remarkable,
      given her retinas were also jeopardized by her profound shock. Additional data
      are needed to understand the risks and benefits of this procedure, but due to
      limited treatment options for poison-induced retinal toxicity and the low
      likelihood for implementation of a controlled randomized trial of HBO2 in this
      population, the procedure may be considered in quinine-induced retinal toxicity.

PMID- 30241127
TI  - Benefit of hyperbaric oxygen therapy treatment in direct traumatic optic
      neuropathy: case report.
AB  - Direct traumatic optic neuropathy (TON) is a devastating condition and clinical
      challenge. Its adequate treatment remains controversial. Hyperbaric oxygen (HBO2)
      therapy has been proposed as an adjunctive treatment for eye disease but has
      rarely been used in optic neuropathy. The patient was a 57-year-old woman who had
      direct TON and brain injury after contusion injury. After receiving delayed HBO2
      therapy her visual acuity got better - from hand motion to 6/60 - along with
      improvement of visual field and color vision. She was treated at 2.5 atmospheres
      absolute for 100 minutes, five times a week, for a total of 61 sessions. Our case
      highlights that HBO2 may be beneficial as an alternative treatment for direct
      TON, particularly when combined with brain injury. Although this entity is
      promising, further randomized controlled trials will be needed to clarify the
      efficacy of HBO2 in the treatment of direct TON.

PMID- 30241128
TI  - Surviving Sepsis Campaign guidelines for a diver with DCI: case report.
AB  - Severe decompression illness (DCI) is an uncommon medical issue affecting divers
      and results mainly from rapid surfacing using inadequate decompression protocols.
      Massive gas embolism with central nervous system involvement often leads to a
      poor prognosis, with permanent residual neurologic defects. Moreover, DCI
      complicated with multiple organ dysfunction syndrome (MODS) is tremendously rare
      and difficult to cure, although hyperbaric oxygen (HBO2) therapy following the
      U.S. Navy Treatment Tables is a consensus. We report a case of severe DCI with
      profound shock and MODS after an initial treatment with HBO2 therapy using U.S.
      Navy Treatment Table 6A. Following the Surviving Sepsis Campaign Guidelines, low
      dose hydrocortisone was administered. Although this treatment went against
      recommendation of the U.S. Navy Diving Manual, it resulted in a dramatic clinical
      improvement. After a second round of HBO2 treatments, the patient was discharged
      from hospital two weeks after the diving accident.

PMID- 30241129
TI  - UHMS member wound scoring system is receiving coverage.

PMID- 30241130
TI  - UHMS Position Statement in full: low-pressure fabric hyperbaric chambers.

PMID- 30241131
TI  - [The experience of using magnetic resonance imaging of the uterus and its
      appendages as an alternative to X-ray hysterosalpingography].
AB  - Objective: Determination of the diagnostic capabilities of magnetic resonance
      imaging of the uterus and its appendages (MRHSG) on devices with the induction of
      the magnetic field 3 Tesla (T) as an alternative to the classic X-ray
      hysterosalpingography, accompanied by a significant radiation dose to the
      patient. Material and Methods: During the period from April 2015 to February 2016
      12 MRHSG was conducted using magnetic resonance imaging apparatus Verio Magnetom
      3T, Siemens company (Diagnostic Center "BarsMed", Kazan, Russia). We used neutral
      and not giving adverse reactions contrast agent - carbon dioxide. The pelvic
      organs - the uterus and fallopian tubes - represent the zone of interest.
      Results: Analysis of the data showed that MRHSG on the apparatus with the
      induction of the magnetic field of 3 T is a highly informative method in the
      diagnosis of tubal patency, allowing fully assess the state of the pelvic organs
      on the whole and identify pathology.The absence of radiation exposure and
      contraindications associated with intolerance to iodinated contrast agents and
      other side effects differs MRHSG from the traditional X-ray method and makes
      MRHSG to be an alternative secure method of diagnosis, which has a number of
      advantages described in the article. Conclusions: MRHSG on the apparatus with the
      induction of the magnetic field of 3 T in diagnosis of obstruction of the
      fallopian tubes and the visualization of the uterus and appendages diseases can
      be optimal and safe alternative to the X-ray hysterosalpingography, which
      accompanied with radiation exposure and is a number of side effects.

PMID- 30241132
TI  - [Features of pathological changes of fibro-cartilaginous tissue knee in patients
      with Baker cyst.]
AB  - Objective: Using magnetic resonance imaging (MRI) to evaluate the characteristics
      of pathological changes of fibro-cartilage of the knee in patients with Baker
      cyst, to assess the compliance of degrees of damage stages of osteoarthritis on a
      scale of Kellgren-Lawrence (K-L), and compare the results with the data of other
      researchers. Material and Methods: This study included patients (38-82 years)
      with a cyst Baker accidentally detected during ultrasound veins of the lower
      extremities. The subjects underwent a single knee MRI. MRI was made in three
      dimensions using 3D gradient-echo protocol. Independent radiologist evaluated the
      presence and severity of chondral defect osteophytosis, damage to the menisci and
      ligaments, intraosseous edema and subchondral cysts. The osteoarthritis stage of
      the knee were identified by X-ray performed in a standing position in the
      standard two projections, with K-L scale. Results: In this study, the results of
      a survey of 20 people, whose average age was 57.2 years. According to the
      radiological scale of K-L two patients were assigned to the stage 0 degree, 5
      people to stage 1, 2, 4 each, and 3 - to stage 3. Synovitis of various severity
      was detected in 85% of the studies. Nineteen visualized the patellar cartilage
      damage, the condyles of the femur and tibia are most commonly affects the joint
      area. Among the most commonly injured ligament anterior cruciate ligament was
      determined - 9 (45%) patients in the same amount of detected intramedullary edema
      condyles femur and tibia. Eighteen subjects had at least one anomaly meniscus
      detectable by MRI, while in 11 (55%) persons were deviations, at least two or
      more regions of the knee examined. Conclusions: Our results suggest that not all
      visualized on MRI degenerative damage to intra fibro-cartilaginous tissue
      correlate positively with the stages of osteoarthritis of the knee, identified by
      standard radiographs and may not significantly affect the onset and progression
      of synovial cyst of the popliteal region.

PMID- 30241133
TI  - [Impact of neutron radiation on the viability of tumor cells cultured in the
      presence of boron-10 isotope].
AB  - Objective: To investigate the impact of a neutron beam formed with the
      accelerator-based epithermal neutron source designed at the G.I. Budker Institute
      of Nuclear Physics (INP) on the viability of human and animal tumor cells
      cultured in the presence of boron-10 isotope. Material and Methods: Human U251
      and T98G glioma cells and Chinese hamster CHO-K1 and V-79 cells were incubated at
      various concentrations in the culture medium containing 10B-enriched L
      boronophenylalanine. The cells were irradiated with a neuron beam using the
      accelerator-based epithermal neuron source. A clonogenic assay was used to
      evaluate the viability of the irradiated cells. The absorbed doses obtained from
      elastic scattering of fast neutrons by substance nuclei and the doses obtained
      from boron neutron capture were calculated using the NMS code. The absorbed doses
      of gamma-radiation were measured with a mixed radiation dosimeter. Results: The
      viability of boron-containing and intact human U251 and T98G cell lines and
      Chinese hamster CHO-K1 and V-79 cells was analyzed after neutron beam radiation.
      Irradiation of all four cell lines were cultured in the presence of 10B was shown
      to reduce their colony-forming capacity compared with the control. Elevated boron
      levels in the culture medium resulted in a significant decrease in the proportion
      of survived cells. Radiation had the most pronounced impact on the proliferative
      capacity of the human U251 glioma cell lines. Conclusion: The cultures of human
      tumor cells and mammalian cells demonstrated that the neutron beam formed with
      the accelerator-based epithermal neutron source designed at the INP, was
      effective in reducing the viability of tumor cells in the presence of 10B.

PMID- 30241134
TI  - [Dynamic single-photon emission computed tomography as a method of identification
      of multivessel coronary artery disease].
AB  - Objective: The aim of this study was to determine the informative value of
      dynamic tomoscintigraphy in detection of multivessel coronary artery disease
      (CAD). Material and Methods: Patients with multivessel CAD (n= 16) and healthy
      volunteers (n= 9) underwent dynamic cardiac single photon emission computed
      tomography with 99mTs-MIBI at rest and during pharmacological stress
      test.Processing of acquired results involved the formation of regions of interest
      from the cavity and the myocardium of the left ventricle used to create activity
      time curves. Coronary flow reserve index was defined as a quotient of two ratios
      of the mean counts from the myocardial region to the integral activity in the
      left ventricular cavity for the studies performed during pharmacological stress
      test and at rest. Results: The mean values of coronary flow reserve index were
      1.86 (1.59; 2.2) in group of healthy volunteers and 1.39 (1.12; 1.69) in patients
      with multivessel CAD. When the value of this index was less than 1.77, the method
      allowed for detection of three-vessel CAD with the sensitivity and specificity
      rates of 81.8% and 66.7%, respectively. Conclusion: Performing the standard
      myocardial perfusion scintigraphy in combination with the method of coronary flow
      reserve index assessment allows for enhancement of the diagnostic value of
      scintigraphic approach in the evaluation of coronary circulation disturbances in
      multivessel CAD.

PMID- 30241135
TI  - India-United States Dialogue on Traditional Medicine: Toward Collaborative
      Research and Generation of an Evidence Base.
AB  - Therapies originating from traditional medical systems are widely used by
      patients in both India and the United States. The first India-US Workshop on
      Traditional Medicine was held in New Delhi, India, on March 3 and 4, 2016, as a
      collaboration between the Ministry of Ayurveda, Yoga and Naturopathy, Unani,
      Siddha, and Homoeopathy (AYUSH) of the Government of India, the US National
      Cancer Institute (NCI), National Institutes of Health, and the Office of Global
      Affairs, US Department of Health and Human Services. It was attended by Indian
      and US policymakers, scientists, academics, and medical practitioners from
      various disciplines. The workshop provided an opportunity to open a dialogue
      between AYUSH and NCI to identify promising research results and potential topics
      for Indo-US collaboration. Recommendations that emerged from the workshop
      underlined the importance of applying rational and scientific approaches for drug
      development; standardizing traditional medicine products and procedures to ensure
      reliability and reproducibility; promotion of collaboration between Indian
      traditional medicine practitioners and researchers and US researchers; greater
      integration of evidence-based traditional medicine practices with mainstream
      medical practices in India; and development of training programs between AYUSH
      and NCI to facilitate crosstraining. Several positive developments took place
      after the thought-provoking deliberations.

PMID- 30241136
TI  - Decreasing Histology Turnaround Time Through Stepwise Innovation and Capacity
      Building in Rwanda.
AB  - PURPOSE: Minimal turnaround time for pathology results is crucial for highest
      quality patient care in all settings, especially in low- and middle-income
      countries, where rural populations may have limited access to health care.
      METHODS: We retrospectively determined the turnaround times (TATs) for anatomic
      pathology specimens, comparing three different modes of operation that occurred
      throughout the development and implementation of our pathology laboratory at the
      Butaro Cancer Center of Excellence in Rwanda. Before opening this laboratory, TAT
      was measured in months because of inconsistent laboratory operations and a
      paucity of in-country pathologists. RESULTS: We analyzed 2,514 individual patient
      samples across the three modes of study. Diagnostic mode 1 (samples sent out of
      the country for analysis) had the highest median TAT, with an overall time of 30
      days (interquartile range [IQR], 22 to 43 days). For diagnostic mode 2 (static
      image telepathology), the median TAT was 14 days (IQR, 7 to 27 days), and for
      diagnostic mode 3 (onsite expert diagnosis), it was 5 days (IQR, 2 to 9 days).
      CONCLUSION: Our results demonstrate that telepathology is a significant
      improvement over external expert review and can greatly assist sites in improving
      their TATs until pathologists are on site.

PMID- 30241138
TI  - Sentinel Lymph Node Biopsy Pathology and 2-Year Postsurgical Recurrence of Breast
      Cancer in Kenyan Women.
AB  - PURPOSE: The goal of this study was to describe the pathologic findings and early
      follow-up experience of patients who underwent a sentinel lymph node biopsy
      (SLNB) at Aga Khan University Hospital (AKUH) between 2008 and 2017. PATIENTS AND
      METHODS: We performed a retrospective analysis of women with breast cancer who
      underwent an SLNB at AKUH between 2008 and 2017. The SLNB was performed on
      patients with stage I and stage II breast cancer, and identification of the
      sentinel lymph node was made by radioactive tracer, blue dye, or both, per
      availability and surgeon preference. Demographic, surgical, and pathologic data,
      including immunohistochemistry of the surgical sample for estrogen receptor,
      progesterone receptor, and human epidermal growth factor receptor 2, were
      abstracted from the patient records. Follow-up data were available for a subset
      of patients. RESULTS: Between 2008 and 2017, six surgeons performed SLNBs on 138
      women, 129 of whom had complete records and were included in the study. Thirty
      one of 129 (24%) had a positive SLNB, including 10 of 73 (14%) with stage I and
      21 of 56 (38%) with stage II disease. Seventy-eight patients (60%) received
      systemic adjuvant chemotherapy and 79 (62%) received radiation therapy, and of
      the 102 patients who were estrogen receptor positive, 86 (85%) received endocrine
      therapy. Seventy-nine patients were observed for > 2 years, and, of these, four
      (5.1%) had a regional recurrence. CONCLUSION: The SLNB positivity rates were
      similar to those of high-income country (HIC) cohorts. However, preliminary data
      suggest that recurrence rates are elevated at AKUH as compared with those of HIC
      cohorts, perhaps because of a lower use of radiotherapy and chemotherapy at AKUH
      compared with HIC cohorts or because of differences in the characteristics of the
      primary tumor in patients at AKUH as compared with those in HICs.

PMID- 30241137
TI  - In Their Own Words: A Qualitative Study of Kenyan Breast Cancer Survivors'
      Knowledge, Experiences, and Attitudes Regarding Breast Cancer Genetics.
AB  - INTRODUCTION: Breast cancer ranks among the most common adult cancers in Kenya.
      Individuals with a family history of the disease are at increased risk. Mutations
      most commonly associated with breast cancer affect BRCA1 and BRCA2; mutations in
      several other genes may also confer breast cancer risk. Genetic testing and
      counseling can help patients understand their risk and assist clinicians in
      choosing therapies. We aimed to uncover what patients know, experience, and think
      with regard to breast cancer genetics in Kenya. METHODS: Participants included
      breast cancer survivors age > 18 years. Participants completed a demographic
      questionnaire before participating in focus group discussions to uncover
      knowledge of, experiences with, and attitudes toward the genetics of breast
      cancer. Data were analyzed by inductive thematic analysis. RESULTS: Four focus
      groups were conducted. Participants had rudimentary knowledge about genetics and
      cancer development, and although they understood breast cancer could be familial,
      many suspected environmental factors causing spontaneous disease. They reported
      limited experience with counseling about genetic risk, perceiving that their
      physicians were too busy to provide comprehensive information. Many indicated
      they promoted cancer screening among family to promote early diagnosis.
      Participants expressed a need for more comprehensive counseling and access to
      genetic testing, recognizing the added clarity it would bring to their families'
      risk of cancer. CONCLUSION: Improved communication from health care teams could
      clarify the risk of cancer for affected families. The introduction of affordable
      genetic testing and counseling for breast cancer in Kenya is welcomed by
      survivors.

PMID- 30241140
TI  - Knowledge Summaries for Comprehensive Breast Cancer Control.
AB  - Breast cancer is the most common cancer in women worldwide, affecting > 1.6
      million women each year, projected to increase to 2.2 million cases annually by
      2025. A disproportionate number of the > 500,000 women who die as a result of
      breast cancer each year reside in low-resource settings. Breast cancer control is
      an important component of cancer control planning and women's health programs,
      and tools are needed across the care continuum to reduce the cancer burden,
      especially in low-resource settings. Cancer control planning is complex and
      multifaceted. Evidence shows that outcomes are improved when prevention, early
      diagnosis, treatment, and palliation are integrated and synchronously developed
      within a country/region's health plan. The Knowledge Summaries for Comprehensive
      Breast Cancer Control are the product of a multiyear collaboration led by the
      Union for International Cancer Control, Breast Health Global Initiative, Pan
      American Health Organization, and Center for Global Health of the US National
      Cancer Institute. Fourteen knowledge summaries distilled from evidence-based,
      resource-stratified guidelines, and aligned with WHO guidance on breast cancer
      control, build a framework for resource prioritization pathways and delivery
      systems for breast cancer control at four levels of available resources: basic,
      limited, enhanced, and maximal. Each summary contains relevant content to inform
      breast cancer policy, clinical care, and advocacy, aiding in the development and
      implementation of policies and programs. These tools provide a common platform
      for stakeholders, including policymakers, administrators, clinicians, and
      advocates to engage in decision making appropriate to their local setting. The
      goal is to facilitate evidence-based policy actions and urgently advance
      implementation of an integrated approach to reduce breast cancer mortality and
      improve quality of life.

PMID- 30241139
TI  - HIV Status and Associated Clinical Characteristics Among Adult Patients With
      Cancer at the Uganda Cancer Institute.
AB  - PURPOSE: HIV increases cancer incidence and mortality. In Uganda, the HIV
      epidemic has led to an elevated incidence of AIDS-defining cancers (ADCs) and non
      AIDS-defining cancers (NADCs). Limited information exists about how frequently
      HIV infection complicates the presentation and manifestations of cancer in sub
      Saharan Africa. METHODS: We abstracted medical records from patients with cancer
      who were age 18 years or older who registered at the Uganda Cancer Institute from
      June through September 2015 to determine the burden of HIV. We used chi2 tests
      and generalized linear models to evaluate factors associated with HIV positivity.
      A sensitivity analysis estimated HIV prevalence in those untested. RESULTS: Among
      1,137 patients with cancer, 23% were HIV infected, 48% were HIV negative, and 29%
      had no recorded HIV status. Of those with recorded HIV status, 32% were HIV
      positive. Forty-two percent (149 of 361 patients) with ADCs were documented as
      HIV infected (51% of those with documented status) compared with 14% (108 of 776
      patients) of those with NADCs (21% of those with documented status). In
      multivariable analysis, HIV infection was associated with ADC diagnosis (adjusted
      prevalence ratio [aPR] compared with NADC, 2.2; 95% CI, 1.5 to 3.0), younger age
      (aPR, 0.9 per decade increase; 95% CI, 0.8 to 1.0), and worse performance status
      scores (aPR, 1.2 per point ECOG increase; 95% CI, 1.0 to 1.5). When sensitivity
      analysis accounted for undocumented HIV status, the expected prevalence of HIV
      infection was 29% (range, 23% to 32%), and almost one fourth of expected HIV
      cases were undiagnosed or unrecorded. CONCLUSION: The prevalence of HIV infection
      among Ugandan patients with cancer is substantially higher than in the general
      population. Patients with cancer and HIV tend to be younger and have poorer
      performance status. Greater awareness of the dual burden of cancer and HIV in
      Uganda and universal testing of patients with cancer may improve outcomes of HIV
      associated malignancies.

PMID- 30241141
TI  - Breast Cancer Pathology Turnaround Time in Botswana.
AB  - PURPOSE: Quality pathology is critical for timely diagnosis and management of
      breast cancer. Few studies have analyzed pathology turnaround time (TAT) in sub
      Saharan Africa. The purpose of this study was to quantify TAT for breast cancer
      specimens processed by the National Health Laboratory and Diagnofirm Laboratory
      in Gaborone, Botswana, and additionally compare TAT before and after 2012 to
      evaluate the effect of pathology scale-up interventions by the Ministry of Health
      and Wellness. METHODS: Retrospective analyses of TAT were performed for breast
      specimens submitted to the two laboratories from 2011 to 2015. TAT was calculated
      as the time from specimen collection and receipt in the laboratory to the date of
      final report sign-out. Descriptive statistics and rank sum test were used to
      compare temporal trends in TAT before and after 2012. RESULTS: A total of 158
      breast biopsy, 219 surgical, and 218 immunohistochemistry (IHC) specimens were
      analyzed. The median TAT in 2015 was 6 and 7 days for biopsy and IHC specimens,
      respectively, and 57.5 days for surgical specimens. There was a significant
      decrease in median TAT for biopsy specimens from 21.5 days in 2011 to 2012
      compared with 8 days in 2013 to 2015 ( P < .001). There was also a significant
      decrease in median TAT for IHC specimens during the same period ( P < .001).
      However, there was no significant decline in median TAT for surgical specimens.
      CONCLUSION: The scale-up of pathology personnel and infrastructure by the
      Ministry of Health and Wellness significantly reduced median TAT for biopsy and
      IHC specimens. TAT for surgical specimens remains suboptimal. Efforts are
      currently under way to decrease TAT for surgical specimens to 7 days.

PMID- 30241142
TI  - Is It Relevant to Keep Advocating Visual Inspection of the Cervix With Acetic
      Acid for Primary Cervical Cancer Screening in Limited-Resource Settings?

PMID- 30241143
TI  - Treatment of Parotid Non-Hodgkin Lymphoma: A Meta-Analysis.
AB  - PURPOSE: This meta-analysis aimed to review the published outcomes of parotid non
      Hodgkin lymphoma (NHL) pertaining to different treatment modalities. MATERIALS
      AND METHODS: A total of 48 journal articles published between 1993 and 2015,
      comprising 742 cases of parotid NHL, were initially evaluated. In total, 108
      patients from 12 studies who had sufficient data for analysis, including age,
      tumor histopathology, treatment modality, and outcome at final follow-up, were
      included. Patients were randomly assigned to different categories on the basis of
      histopathology and treatment modality. Groups were compared using Kaplan-Meier
      survival curve analysis and the Mann-Whitney U test. RESULTS: Log-rank tests
      demonstrated that for early-stage (I and II) parotid NHL of all histopathology
      variants, radiation therapy significantly improved the survival rate versus
      chemotherapy ( P = .043), as well as combined treatment with chemotherapy and
      radiation therapy ( P = .023). For early-stage diffuse large B-cell lymphoma,
      combined treatment significantly improved survival versus single treatment ( P =
      .028). No treatment was received by seven patients with early-stage mucosa
      associated lymphoid tissue lymphoma after undergoing parotidectomy. When the
      clinical outcomes of these patients were compared with those of other patients
      with the same histology who underwent further treatment, no significant
      differences were noted in survival outcomes. CONCLUSION: Radiation therapy seems
      to be a valid treatment of early-stage parotid NHL. However, for diffuse large B
      cell lymphoma, survival was higher with combined treatment versus single
      treatment. For early-stage parotid mucosa-associated lymphoid tissue lymphoma,
      complete excision of the tumor through superficial parotidectomy may have similar
      survival outcome.

PMID- 30241144
TI  - Bortezomib Prescription Pattern for the Treatment of Multiple Myeloma by
      Hematologists in Nigeria.
AB  - PURPOSE: Novel therapy has dramatically changed the outcome of patients with
      myeloma. Current National Comprehensive Cancer Network guidelines give bortezomib
      based combinations a central role in the management of multiple myeloma (MM). The
      aim of this survey is to assess the use of bortezomib for the treatment of MM by
      hematologists practicing in Nigeria. MATERIALS AND METHODS: This is a cross
      sectional observational survey. A structured, prevalidated questionnaire was self
      administered to different cadres of hematologists. Data collected were analyzed
      using SPSS software version 21 (IBM, Chicago, IL). RESULTS: There were 54
      respondents from 24 centers across the country. The most frequently used drugs
      for first-line therapy were thalidomide (66.7%), dexamethasone (54.2%), and
      bortezomib (48%), and a combination of bortezomib, thalidomide, and dexamethasone
      (16.7%) was the most frequently used first-line regimen. Of the 54 hematologists,
      39 (72.2%) had prescribed bortezomib previously; no one had used bortezomib as
      monotherapy. Drug unavailability (86.7%) and cost (46.7%) were the major reasons
      for those who had not prescribed bortezomib. Approximately 56.4% of responders
      had patients who had experienced adverse effects, of which neuropathy was the
      most common (86.3%). CONCLUSION: Bortezomib, thalidomide, and dexamethasone was
      the most frequently used first-line regimen to treat myelomatosis. Thalidomide
      and dexamethasone were the most frequently used drugs in myeloma treatment.
      Despite poor access to health care, coupled with the high cost and poor
      availability of bortezomib in our low- or middle-income country, those who
      prescribed bortezomib did so frequently (in more than half of their patients).

PMID- 30241145
TI  - Histology and Cytopathology Capacity in the Public Health Sector in Kenya.
AB  - PURPOSE: Histology and cytopathology services are necessary for cancer diagnosis
      and treatment. However, the current capacity of Kenya's pathology laboratories is
      unknown. A national survey was conducted among public sector pathology
      laboratories to assess their capacity to perform histology, fine-needle
      aspiration, and bone marrow aspiration. METHODS: Between April and June 2017, we
      identified all public hospitals that provide pathology services in Kenya. In
      total, two national and 13 county referral hospitals met the inclusion criteria
      and were sent a standardized, pretested, self-administered questionnaire.
      RESULTS: A total of 11 hospitals (73%) completed the survey. The reported total
      caseload of histology, fine-needle aspiration, and bone marrow aspiration for
      2016 was 26,472. All of the facilities staffed a pathologist and were providing
      cancer-related diagnostic services. Nine (82%) of the hospitals maintain a
      register of diagnosed cancer cases, but only one (11%) of those uses an
      electronic system. Six (55%) of the surveyed hospitals were able to perform
      histology with a median turnaround time of 14 days. Six (55%) laboratories
      regularly referred some specimens elsewhere for interpretation, but three of
      these centers relied on patients for transportation of the specimen to the
      referral institution. No laboratories were accredited by an external
      organization; however, 10 (91%) of the laboratories were working toward achieving
      accreditation, but only for clinical pathology services. CONCLUSION: This study
      describes the current status of histology and cytopathology capacity in Kenya's
      public sector hospitals. It provides useful baseline information needed by the
      Ministry of Health to develop necessary capacity building and referral
      strengthening interventions. A high proportion of hospitals are working to
      achieve accreditation points toward their commitment to providing quality
      services to the Kenyan public.

PMID- 30241146
TI  - Posterior Reversible Encephalopathy Syndrome in Pediatric Cancer: Clinical and
      Radiologic Findings.
AB  - PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is associated with a
      range of medical conditions and medications. In this retrospective analysis, we
      present 19 pediatric patients with PRES who had undergone chemotherapy. METHODS:
      We identified four female and 15 male patients diagnosed with PRES on the basis
      of clinical and radiologic features. Patient charts were reviewed from January
      2013 to June 2016 after authorization from the institutional review board.
      RESULTS: The average age of patients with PRES was 7 years. Primary diagnoses
      were non-Hodgkin lymphoma (n = 9), acute pre-B-cell leukemia (n = 5), relapsed
      pre-B-cell leukemia (n = 2), Hodgkin lymphoma (n = 2), and Ewing sarcoma (n = 1).
      PRES occurred during induction chemotherapy in 12 patients. Sixteen patients had
      hypertension when they developed PRES. Most of these patients (n = 13) were
      receiving corticosteroids on diagnosis of PRES. Common clinical features were
      hypertension, seizures, and altered mental status. With the exclusion of three
      patients, all others required antiepileptic therapy. Ten of these patients
      underwent additional magnetic resonance imaging. Ten patients are still alive.
      CONCLUSION: In patients who presented to our center with signs and symptoms of
      hypertension, seizures, visual loss, or altered mental status, PRES was mostly
      seen in those who were undergoing systemic and intrathecal chemotherapy.
      Approximately 40% of the patients had reversal of clinical and radiologic
      findings. Antiepileptic medications were discontinued after being seizure free
      for approximately 6 months.

PMID- 30241147
TI  - Association Between HIV Infection and Cancer Stage at Presentation at the Uganda
      Cancer Institute.
AB  - PURPOSE: The HIV epidemic has contributed to the increasing incidence of cancer
      in sub-Saharan Africa, where most patients with cancer present at an advanced
      stage. However, improved access to HIV care and treatment centers in sub-Saharan
      Africa may facilitate earlier diagnosis of cancer among patients who are HIV
      positive. To test this hypothesis, we characterized the stage of cancer and
      evaluated the factors associated with advanced stage at presentation among
      patients in Uganda. METHODS: We conducted a retrospective analysis of adult
      patients with any of four specific cancers who presented for care in Kampala,
      Uganda, between 2003 and 2010. Demographic, clinical, and laboratory data were
      abstracted from the medical record, together with the outcome measure of advanced
      stage of disease (clinical stage III or IV). We identified measures for inclusion
      in a multivariate logistic regression model. RESULTS: We analyzed 731 patients
      with both AIDS-defining cancers (cervical [43.1%], and non-Hodgkin lymphoma
      [18.3%]), and non-AIDS-defining cancers (breast [30.0%] and Hodgkin lymphoma
      [8.6%]). Nearly 80% of all patients presented at an advanced stage and 37% had
      HIV infection. More than 90% of patients were symptomatic and the median duration
      of symptoms before presentation was 5 months. In the multivariate model, HIV
      positive patients were less likely to present at an advanced stage as were
      patients with higher hemoglobin and fewer symptoms. CONCLUSION: Patients with
      limited access to primary care may present with advanced cancer because of a
      delay in diagnosis. However, patients with HIV now have better access to clinical
      care. Use of this growing infrastructure to increase cancer screening and
      referral is promising and deserves continued support, because the prognosis of
      HIV-positive patients with advanced cancer is characterized by poor survival
      globally.

PMID- 30241148
TI  - Outcomes of Low-Intensity Treatment of Acute Lymphoblastic Leukemia at Butaro
      Cancer Center of Excellence in Rwanda.
AB  - PURPOSE: Children with acute lymphoblastic leukemia (ALL) in low-income countries
      have disproportionately lower cure rates than those in high-income countries. At
      Butaro Cancer Center of Excellence (BCCOE), physicians treated patients with ALL
      with the first arm of the Hunger Protocol, a graduated-intensity method tailored
      for resource-limited settings. This article provides the first published
      outcomes, to our knowledge, of patients with ALL treated with this protocol.
      METHODS: This is a retrospective descriptive study of patients with ALL enrolled
      at BCCOE from July 1, 2012 to June 30, 2014; data were collected through December
      31, 2015. Descriptive statistics were used to calculate patient demographics,
      disease characteristics, and outcomes; event-free survival was assessed at 2
      years using the Kaplan-Meier method. RESULTS: Forty-two consecutive patients with
      ALL were included. At the end of the study period, 19% (eight) were alive without
      evidence of relapse: three completed treatment and five were continuing
      treatment. Among the remaining patients, 71% (30) had died and 10% (four) were
      lost to follow-up. A total of 83% (25) of the deaths were disease related, 3%
      (one) treatment-related, and 13% (four) unclear. Event-free survival was 22% (95%
      CI, 11% to 36%), considering lost to follow-up as an event, and 26% (95% CI, 13%
      to 41%) if lost to follow-up is censored. CONCLUSION: As expected, relapse was
      the major cause of failure with this low-intensity regimen. However, toxicity was
      acceptably low, and BCCOE has decided to advance to intensity level 2. These
      results reflect the necessity of a data-driven approach and a continual
      improvement process to care for complex patients in resource-constrained
      settings.

PMID- 30241149
TI  - Novel Pilot Curriculum for International Education of Lymphoma Management Using E
      Contouring.
AB  - PURPOSE: The International Lymphoma Radiation Oncology Group (ILROG) published
      consensus guidelines on the management of Hodgkin disease (HD) and nodal non
      Hodgkin lymphoma (NHL), which became the most downloaded articles from
      International Journal of Radiation Oncology, Biology, and Physics. E-contouring
      workshops allow for interactive didactic sessions, allowing participants to see
      case-based contouring in real time. A pilot 1-hour curriculum was developed with
      the objective of reviewing ILROG guidelines for HD and NHL management with
      incorporation of e-contouring tools. This represents the first international
      education intervention in Spanish using e-contouring with a pre- and
      postintervention questionnaire. METHODS: A 1-hour presentation was prepared in
      Spanish reviewing the ILROG recommendations for HD and NHL. The review was
      followed by the author's demonstration of contour creation using patients with HD
      and NHL prepared for the American Society for Radiation Oncology's 2015 e
      contouring lymphoma session. A five- question evaluation was prepared and
      administered before and after intervention. A two-tailed paired t test was
      performed to evaluate any significant change in test value before and after
      intervention. RESULTS: A total of nine quizzes were collected before and after
      the intervention. The average test score before the intervention was 75.6%, and
      the average test score after the intervention was 86.7% ( P = .051). Four
      students scored 100% on both the pre- and postintervention evaluations, and no
      student had a decrease in score from pre- to postintervention evaluation. The
      topic with the lowest score tested dose consideration. CONCLUSION: A substantial
      but nonsignificant improvement in test evaluation was seen with this pilot
      curriculum. This pilot intervention identified obstacles for truly interactive
      didactic sessions that, when addressed, can lead to fully developed interactive
      didactic sessions.

PMID- 30241150
TI  - Randomized Phase IIA Trial of Gemcitabine Compared With Bleomycin Plus
      Vincristine for Treatment of Kaposi's Sarcoma in Patients on Combination
      Antiretroviral Therapy in Western Kenya.
AB  - PURPOSE: Kaposi's sarcoma (KS) is a spindle cell tumor resulting from growth
      dysregulation in the setting of infection with human herpes virus-8 (also called
      KS herpes virus). Advanced KS is characterized by poor responses to
      antiretroviral therapy and some of the chemotherapy readily accessible to
      patients in low-resource areas. Gemcitabine induced partial and complete
      regression of AIDS-associated KS (AIDS-KS) in 11 of 24 patients in a pilot study.
      The current study compares the antimetabolite gemcitabine with the standard care
      bleomycin and vincristine (BV) in the treatment of chemotherapy-naive patients
      with AIDS-KS in a resource-limited setting. PATIENTS AND METHODS: Patients with
      persistent or progressive KS despite treatment with combined antiretroviral
      therapy were randomly assigned to receive gemcitabine 1,000 mg/m2 or bleomycin 15
      IU/ m2 and vincristine 1.4 mg/m2 given twice weekly. The main end point was
      objective response by bidirectional measurement, adverse events, and quality of
      life after three cycles of chemotherapy. RESULTS: Of 70 participants enrolled, 36
      received gemcitabine and 34 received BV. Complete response was achieved in 12
      patients (33.3%) in the gemcitabine arm and six (17.6%) in the BV arm ( P =
      .175). The partial response rate was 52.8% (n = 19) in the gemcitabine arm and
      58.8% (n = 20) in the BV arm. Both study arms reported similar neurologic and
      hematologic adverse events; there was statistically significant baseline to post
      treatment improvement in health-related quality-of-life scores. CONCLUSION: The
      results of this randomized, phase IIA trial demonstrate gemcitabine activity in
      chemotherapy-naive patients with AIDS-KS, on the basis of response rates, adverse
      events, and health-related quality-of-life scores.

PMID- 30241152
TI  - Biosimilar Drugs: What Would Be a Reasonable Extrapolation?

PMID- 30241153
TI  - First Report of Parkinsonism Associated With Indoximod, an Immune-Modulating
      Agent.

PMID- 30241151
TI  - Impact of Geographic Regions on Overall Survival in Patients With Metastatic
      Renal Cell Carcinoma: Results From an International Clinical Trials Database.
AB  - PURPOSE: Health determinants vary according to geographic region and may affect
      the outcomes of patients with metastatic renal cell carcinoma (mRCC) treated
      during clinical trials of targeted therapy. Here, we investigate the overall
      survival (OS) of patients with mRCC treated in the era of targeted therapy by
      geographic region. METHODS: We conducted a pooled analysis of patients with mRCC
      who were treated during phase II or III clinical trials. Clinical characteristics
      and survival data were collected. Statistical analyses were performed with the
      Kaplan-Meier method and log-rank test in univariable analysis. RESULTS: Overall,
      4,736 patients were included in the analysis. Patient characteristics differed
      according to geographic region. No statistically significant differences in OS
      were observed when the United States/Canada (USC) was compared with the following
      other regions: Latin America, Asia/Oceania/Africa, and Eastern Europe. In a
      univariable analysis, OS differed among patients enrolled in trials in USC
      compared with Western Europe (20.3 v 17.4 months; hazard ratio, 1.15; 95% CI,
      1.03 to 1.3; P = .015), but it did not differ in a multivariable analysis. All
      grade treatment-related adverse events (AEs) were observed more frequently in
      USC. There were no significant differences in grade 3 to 5 AEs among groups.
      CONCLUSION: Despite different baseline characteristics, OS was similar among
      patients enrolled in clinical trials across different geographic regions. Access
      to clinical trials as well as disease biology, AE reporting, and quality of care
      may contribute to potential differences in outcomes.

PMID- 30241154
TI  - Chemotherapy in Nonmetastatic Osteosarcoma: Recent Advances and Implications for
      Developing Countries.
AB  - PURPOSE: Osteosarcoma (OS) is a relatively chemosensitive primary bone tumor,
      with the peak age of onset occurring in late childhood and early adolescence. The
      treatment paradigm of nonmetastatic OS has typically been multimodality therapy,
      including neoadjuvant and adjuvant chemotherapy with definitive surgery. Over the
      years, various permutations and combinations of chemotherapeutic agents have been
      used. However, the majority of recent trials have still used high-dose
      methotrexate as the backbone, with cisplatin and doxorubicin (MAP). In the last
      decade, various strategies targeted to improving outcomes in OS have included the
      addition of a fourth drug to the three-drug MAP regimen, changing therapy
      according to histopathologic response and the addition of immunotherapies.
      Through this review, we sought to underscore a few pertinent issues related to
      chemotherapy in nonmetastatic OS, with special reference to challenges confronted
      in Indian settings. METHODS: We reviewed the literature, focusing on studies
      comparing high-dose methotrexate and non-high-dose methotrexate-containing
      regimens. In addition, this review focuses on non-methotrexate-containing triple
      drug therapy. RESULTS: Although a high-dose methotrexate regimen has become
      standard of care in developed countries, there are few data to suggest that it is
      superior to a non-high-dose methotrexate regimen. CONCLUSION: Developing
      countries with lack of infrastructure and logistics for high-dose methotrexate
      might resort to non-high-dose methotrexate-containing regimens with a
      simultaneous focus on early detection, decreasing abandonment, multidisciplinary
      clinics, improved surgery, and meticulous pathologic evaluations.

PMID- 30241155
TI  - Improving Global Outcomes in Cervical Cancer: The Time Has Come for International
      Federation of Gynecology and Obstetrics Staging to Formally Incorporate Advanced
      Imaging.

PMID- 30241156
TI  - Primary Febrile Neutropenia Prophylaxis for Patients Who Receive FEC-D
      Chemotherapy for Breast Cancer: A Systematic Review.
AB  - PURPOSE: Despite widespread use of fluorouracil, epirubicin, cyclophosphamide,
      docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary
      febrile neutropenia (FN) prophylaxis remains unknown. A systematic review was
      therefore performed. METHODS: Embase, Ovid MEDLINE, PubMed, Cochrane Database of
      Systematic Reviews, Cochrane Register of Controlled Trials, and conference
      proceedings were searched from 1946 to April 2016 for trials that reported the
      effectiveness of primary FN prophylaxis with FEC-D chemotherapy. Outcome measures
      were incidence of FN; treatment-related hospitalizations; chemotherapy dose
      delays, reductions, and discontinuations; and adverse events from prophylaxis.
      RESULTS: Of 2,205 identified citations, eight studies (n = 1,250) met our
      eligibility criteria. Three additional studies (n = 293) were identified from a
      prior systematic review. Three randomized controlled trials (n = 576), one phase
      IV single-arm trial (n = 69), one prospective observational study (n = 37), and
      six retrospective studies (n = 861) were identified. Agents investigated were
      pegfilgrastim (n = 108), filgrastim (n = 1,119), and ciprofloxacin (n = 89). The
      heterogeneity of studies meant that a narrative synthesis of results was
      performed. Median FN rates for patients who received FEC-D with and without
      primary prophylaxis were 10.1% (interquartile range [IQR], 3.9% to 22.6%) and
      23.9% (IQR, 9.2% to 27.3%), respectively. In the absence of primary prophylaxis,
      FN was more common during docetaxel than during FEC. Data from six studies showed
      a median rate of dose reductions and delays of 6.1% (IQR, 3.1% to 14.3%) and
      19.3% (IQR, 10.5% to 32.8%), respectively, that occurred as a consequence of FN.
      Toxicity from prophylaxis itself was rarely reported. CONCLUSION: Primary FN
      prophylaxis is effective in patients who receive FEC-D chemotherapy. The paucity
      of prospective data makes optimal recommendations about the choice and timing of
      prophylaxis challenging.

PMID- 30241157
TI  - Barriers to Scale of Digital Health Systems for Cancer Care and Control in Last
      Mile Settings.
AB  - The growing cancer epidemic is a major public health challenge globally but
      especially in low- and middle-income countries where patients often have to make
      long and complex journeys to receive care. Extending cancer prevention,
      diagnosis, and treatment to low- and middle-income countries through innovative
      solutions such as digital health systems is an urgent health priority. We contend
      that such digital systems will achieve success and scale only when existing gaps
      in cancer care and control policies and practices are addressed to strengthen
      health systems and improve outcomes. We call for concerted action to focus on the
      effective implementation of cancer care and control policies and practice in last
      mile settings to improve pathways to care for people with and at risk for cancer.

PMID- 30241159
TI  - Positive Tumor Response to Combined Checkpoint Inhibitors in a Patient With
      Refractory Alveolar Soft Part Sarcoma: A Case Report.

PMID- 30241158
TI  - Differences in Perception of Breast Cancer Among Muslim and Christian Women in
      Ghana.
AB  - PURPOSE: The burden of breast cancer continues to increase in low- and middle
      income countries (LMICs), where women present with more advanced disease and have
      worse outcomes compared with women from high-income countries. In the absence of
      breast cancer screening in LMICs, patients must rely on self-detection for early
      breast cancer detection, followed by a prompt clinical diagnostic work-up. Little
      is known about the influence of religious beliefs on women's perceptions and
      practices of breast health. METHODS: A cross-sectional survey was administered to
      female members of Islamic and Christian organizations in Ghana. Participants were
      asked about their personal experience with breast concerns, knowledge of breast
      cancer, performance of breast self-examination, and experience with clinical
      breast exam. RESULTS: The survey was administered to 432 Muslim and 339 Christian
      women. Fewer Muslim women knew someone with breast cancer (31% v 66%; P < .001)
      or had previously identified a concerning mass in their breast (16% v 65%; P <
      .001). Both groups believed that new breast masses should be evaluated at clinic
      (adjusted odds ratio [AOR], 1.08; 95% CI, 0.58 to 2.01), but Muslim women were
      less likely to know that breast cancer can be effectively treated (AOR, 0.34; 95%
      CI, 0.23 to 0.50). Muslim women were less likely to have performed breast self
      examination (AOR, 0.51; 95% CI, 0.29 to 0.88) or to have undergone clinical
      breast exam (AOR, 0.48; 95% CI, 0.27 to 0.84). CONCLUSION: Muslim women were
      found to be less likely to participate in breast health activities compared with
      Christian women, which highlights the need to consider how religious customs
      within subpopulations might impact a woman's engagement in breast health
      activities. As breast awareness initiatives are scaled up in Ghana and other
      LMICs, it is essential to consider the unique perception and participation
      deficits of specific groups.

PMID- 30241161
TI  - Infrared Coagulation: A Treatment Option for Cervical Intraepithelial Neoplasia.

PMID- 30241160
TI  - Prostate Cancer in Southern Africa: Does Africa Hold Untapped Potential to Add
      Value to the Current Understanding of a Common Disease?

PMID- 30241162
TI  - Underuse of Radiation Therapy After Breast Conservation Surgery in Puerto Rico: A
      Puerto Rico Central Cancer Registry-Health Insurance Linkage Database Study.
AB  - PURPOSE: To identify rates of postoperative radiation therapy (RT) after breast
      conservation surgery (BCS) in women with stage I or II invasive breast cancer
      treated in Puerto Rico and to examine the sociodemographic and health services
      characteristics associated with variations in receipt of RT. METHODS: The Puerto
      Rico Central Cancer Registry-Health Insurance Linkage Database was used to
      identify patients diagnosed with invasive breast cancer between 2008 and 2012 in
      Puerto Rico. Claims codes identified the type of surgery and the use of RT.
      Logistic regression models were used to examine the independent association
      between sociodemographic and clinical covariates. RESULTS: Among women who
      received BCS as their primary definitive treatment, 64% received adjuvant RT.
      Significant predictors of RT after BCS included enrollment in Medicare (odds
      ratio [OR], 2.14; 95% CI, 1.46 to 3.13; P <= .01) and dual eligibility for
      Medicare and Medicaid (OR, 1.61; 95% CI, 1.14 to 2.27; P < .01). In addition, it
      was found that RT was more likely to have been received in certain geographic
      locations, including the Metro-North (OR, 2.20; 95% CI, 1.48 to 3.28; P < .01),
      North (OR, 1.78; 95% CI, 1.20 to 2.64; P < .01), West (OR, 4.04; 95% CI, 2.61 to
      6.25; P < .01), and Southwest (OR, 2.79; 95% CI, 1.70 to 4.59; P < .01).
      Furthermore, patients with tumor size > 2.0 cm and <= 5.0 cm (OR, 0.61; 95% CI,
      0.40 to 0.93; P = .02) and those with tumor size > 5.0 cm (OR, 0.37; 95% CI, 0.15
      to 0.92; P = .03) were found to be significantly less likely to receive RT.
      CONCLUSION: Underuse of RT after BCS was identified in Puerto Rico. Patients
      enrolled in Medicare and those who were dually eligible for Medicaid and Medicare
      were more likely to receive RT after BCS compared with patients with Medicaid
      alone. There were geographic variations in the receipt of RT on the island.

PMID- 30241163
TI  - Stemming the Wave of Cervical Cancer: Human Papillomavirus Vaccine Introduction
      in India.

PMID- 30241164
TI  - Global Challenges for Cancer Imaging.
AB  - Imaging plays many essential roles in nearly all aspects of high-quality cancer
      care. However, challenges to the delivery of optimal cancer imaging in both
      developing and advanced countries are manifold. Developing countries typically
      face dramatic shortages of both imaging equipment and general radiologists, and
      efforts to improve cancer imaging in these countries are often complicated by
      poor infrastructure, cultural barriers, and other obstacles. In advanced
      countries, on the other hand, although imaging equipment and general radiologists
      are typically accessible, the complexity of oncologic imaging and the need for
      subspecialists in the field are largely unrecognized; as a result, training
      opportunities are lacking, and there is a shortage of radiologists with the
      necessary subspecialty expertise to provide optimal cancer care and participate
      in advanced clinical research. This article is intended to raise awareness of
      these challenges and catalyze further efforts to address them. Some promising
      strategies and ongoing efforts are reviewed, and some specific actions are
      proposed.

PMID- 30241165
TI  - Advancing Reliable Data for Cancer Control in the Central America Four Region.
AB  - The Central America Four (CA-4) region, comprising Guatemala, Honduras, El
      Salvador, and Nicaragua, is the largest low- and middle-income country region in
      the Western Hemisphere, with over 36 million inhabitants. The CA-4 nations share
      a common geography, history, language, and development indices, and unified with
      open borders in 2006. The growing CA-4 cancer burden among the noncommunicable
      diseases is expected to increase 73% by 2030, which argues for a regional
      approach to cancer control. This has driven efforts to establish population-based
      cancer registries as a central component of the cancer control plans. The
      involvement of international and academic partners in an array of initiatives to
      improve cancer information and control in the CA-4 has accelerated over the past
      several years. Existing data underscore that the infectious cancers (cervical,
      stomach, and liver) are a particular burden. All four countries have committed to
      establishing regional population-based cancer registries and have advanced
      significantly in pediatric cancer registration. The challenges common to each
      nation include the lack of national cancer control plans and departments,
      competing health priorities, lack of trained personnel, and sustainability
      strategies. General recommendations to address these challenges are outlined. The
      ongoing regional, international, and academic cooperation has proven helpful and
      is expected to continue to be a powerful instrument to contribute to the design
      and implementation of long-term national cancer control plans.

PMID- 30241166
TI  - Breast Cancer Beliefs as Potential Targets for Breast Cancer Awareness Efforts to
      Decrease Late-Stage Presentation in Uganda.
AB  - PURPOSE: To assess breast cancer beliefs in Uganda and determine whether these
      beliefs are associated with factors potentially related to nonparticipation in
      early detection. METHODS: A survey with open- and close-ended items was conducted
      in a community sample of Ugandan women to assess their beliefs about breast
      cancer. Linear regression was used to ascertain associations between breast
      cancer beliefs and demographic factors potentially associated with early
      detection, including socioeconomic factors, health care access, prior breast
      cancer knowledge, and personal detection practices. RESULTS: Of the 401 Ugandan
      women surveyed, most had less than a primary school education and received
      medical care at community health centers. Most women either believed in or were
      unsure about cultural explanatory models for developing breast cancer (> 82%),
      and the majority listed these beliefs as the most important causes of breast
      cancer (69%). By comparison, <= 45% of women believed in scientific explanatory
      risks for developing breast cancer. Although most believed that regular screening
      and early detection would find breast cancer when it is easy to treat (88% and
      80%, respectively), they simultaneously held fatalistic attitudes toward their
      own detection efforts, including belief or uncertainty that a cure is impossible
      once they could self-detect a lump (54%). Individual beliefs were largely
      independent of demographic factors. CONCLUSION: Misconceptions about breast
      cancer risks and benefits of early detection are widespread in Uganda and must be
      addressed in future breast cancer awareness efforts. Until screening programs
      exist, most breast cancer will be self-detected. Unless addressed by future
      awareness efforts, the high frequency of fatalistic attitudes held by women
      toward their own detection efforts will continue to be deleterious to breast
      cancer early detection in sub-Saharan countries like Uganda.

PMID- 30241168
TI  - Chemotherapy in a Patient With G6PD Deficiency and Advanced Testicular Cancer.

PMID- 30241171
TI  - Rethinking the ASCO Resource-Stratified Cervical Cancer Screening Guidelines in
      the Context of Existing Health Infrastructure in Basic Settings.

PMID- 30241170
TI  - Metastatic Breast Cancer Presenting As Orbital Mass: A Case Report With
      Literature Review.

PMID- 30241169
TI  - Implementation of Multicolor Melt Curve Analysis for High-Risk Human Papilloma
      Virus Detection in Low- and Middle-Income Countries: A Pilot Study for Expanded
      Cervical Cancer Screening in Honduras.
AB  - PURPOSE: Cervical cancer is a leading cause of cancer-related mortality in low-
      and middle-income countries (LMICs) and screening in LMICs is extremely limited.
      We aimed to implement on-site high-risk human papillomavirus (hrHPV) DNA testing
      in cohorts of women from an urban factory and from a rural village. METHODS: A
      total of 802 women were recruited for this study in partnership with La Liga
      Contra el Cancer through the establishment of women's health resource fairs at
      two locations in Honduras: a textile factory (n = 401) in the city of San Pedro
      Sula and the rural village of El Rosario (n = 401) in Yoro. Participants received
      a routine cervical examination during which three sterile cytobrushes were used
      to collect cervical samples for testing. hrHPV genotyping was performed using a
      hrHPV genotyping assay and a real-time polymerase chain reaction instrument.
      RESULTS: hrHPV status across all participants at both sites was 13% hrHPV
      positive and 67% hrHPV negative. When hrHPV status was compared across all three
      testing sites, hrHPV-positive rates were approximately equal among the factory
      (13%), village (12%), and confirmatory testing at Dartmouth-Hitchcock Medical
      Center (Lebanon, NH; 14%). hrHPV genotype was compared across sites, with HPV16
      showing the highest infection rate (15%), followed by HPV59 (12%), and HPV68
      (11%). There was a low prevalence of HPV18 observed in both populations compared
      with the hrHPV-positive population in the United States. CONCLUSION: In
      collaboration with oncologists and pathologists from La Liga Contra el Cancer, we
      were able to provide a continuum of care once health-fair testing was performed.
      We established a method and implementation plan for hrHPV testing that is
      sustainable in LMICs.

PMID- 30241172
TI  - Crizotinib-Induced Fulminant Hepatic Failure: A Rare Adverse Event.

PMID- 30241173
TI  - Prevalence of Complementary Medicine Use in Patients With Cancer: A Turkish
      Comprehensive Cancer Center Experience.
AB  - PURPOSE: Complementary and alternative medicine (CAM) has been popular among
      patients with cancer for several decades. The objectives of this study were to
      evaluate the prevalence of CAM use and to identify the factors affecting CAM use
      in a large patient cohort seen at a comprehensive cancer center in Turkey.
      PATIENTS AND METHODS: An investigator-designed survey was completed by volunteer
      patients who visited the outpatient clinic in the medical oncology department.
      CAM use encompassed pharmacologic agents including vitamins, dietary supplements,
      and herbal products or nonpharmacologic methods like prayer, meditation,
      hypnosis, massage, or acupuncture. RESULTS: Of 1,499 patients who answered the
      survey, 1,433 (96%) used nonpharmacologic CAM and 60 (4%) used pharmacologic CAM
      (pCAM). The most frequent types of CAM used were prayer (n = 1,433) followed by
      herbal products (n = 42). pCAM use was not significantly associated with age ( P
      = .63), sex ( P = .15), diagnosis ( P = .15), or income level ( P = .09).
      However, it was significantly associated with the level of education ( P = .0067)
      and employment status ( P < .001). Patients with higher education levels used
      more pCAM products ( P = .025). Among 60 pCAM users, six patients (10%) used pCAM
      for more than 2 years and 22 (36%) did not consult their physicians about their
      pCAM use. Only nine patients (15%) reported unpleasant adverse effects related to
      pCAM. CONCLUSION: Although CAM use was high among our patients, prevalence of
      pCAM use was lower than expected. Patients with higher education levels tended to
      use more pCAM.

PMID- 30241167
TI  - Survey of Fertility Preservation Options Available to Patients With Cancer Around
      the Globe.
AB  - PURPOSE: Oncofertility focuses on providing fertility and endocrine-sparing
      options to patients who undergo life-preserving but gonadotoxic cancer treatment.
      The resources needed to meet patient demand often are fragmented along
      disciplinary lines. We quantify assets and gaps in oncofertility care on a global
      scale. METHODS: Survey-based questionnaires were provided to 191 members of the
      Oncofertility Consortium Global Partners Network, a National Institutes of Health
      funded organization. Responses were analyzed to measure trends and regional
      subtleties about patient oncofertility experiences and to analyze barriers to
      care at sites that provide oncofertility services. RESULTS: Sixty-three responses
      were received (response rate, 25%), and 40 were analyzed from oncofertility
      centers in 28 countries. Thirty of 40 survey results (75%) showed that formal
      referral processes and psychological care are provided to patients at the
      majority of sites. Fourteen of 23 respondents (61%) stated that some fertility
      preservation services are not offered because of cultural and legal barriers. The
      growth of oncofertility and its capacity to improve the lives of cancer survivors
      around the globe relies on concentrated efforts to increase awareness, promote
      collaboration, share best practices, and advocate for research funding.
      CONCLUSION: This survey reveals global and regional successes and challenges and
      provides insight into what is needed to advance the field and make the discussion
      of fertility preservation and endocrine health a standard component of the cancer
      treatment plan. As the field of oncofertility continues to develop around the
      globe, regular assessment of both international and regional barriers to quality
      care must continue to guide process improvements.

PMID- 30241174
TI  - Lack of Access to Targeted Cancer Treatment Modalities in the Developing World in
      the Era of Precision Medicine: Real-Life Lessons From Bosnia.

PMID- 30241175
TI  - Effectiveness of Sorafenib in Hepatic Hemangioma.

PMID- 30241176
TI  - Leverage of an Existing Cervical Cancer Prevention Service Platform to Initiate
      Breast Cancer Control Services in Zambia: Experiences and Early Outcomes.
AB  - PURPOSE: In 2005, the Cervical Cancer Prevention Program in Zambia (CCPPZ) was
      implemented and has since provided cervical cancer screen-and-treat services to
      more than 500,000 women. By leveraging the successes and experiences of the
      CCPPZ, we intended to build capacity for the early detection and surgical
      treatment of breast cancer. METHODS: Our initiative sought to build capacity for
      breast cancer care through the (1) formation of a breast cancer advocacy alliance
      to raise awareness, (2) creation of resource-appropriate breast cancer care
      training curricula for mid- and high-level providers, and (3) implementation of
      early detection and treatment capacity within two major health care facilities.
      RESULTS: Six months after the completion of the initiative, the following
      outcomes were documented: Breast health education and clinical breast examination
      (CBE) services were successfully integrated into the service platforms of four
      CCPPZ clinics. Two new breast diagnostic centers were opened, which provided
      access to breast ultrasound, ultrasound-guided core needle biopsy, and needle
      aspiration. Breast health education and CBE were provided to 1,955 clients, 167
      of whom were evaluated at the two diagnostic centers; 55 of those evaluated
      underwent core-needle biopsy, of which 17 were diagnosed with invasive cancer.
      Newly trained surgeons performed six sentinel lymph node mappings, eight sentinel
      lymph node dissections, and 10 breast conservation surgeries (lumpectomies).
      CONCLUSION: This initiative successfully established clinical services in Zambia
      that are critical for the early detection and surgical management of breast
      cancer.

PMID- 30241177
TI  - Pediatric Cancer in Northern Tanzania: Evaluation of Diagnosis, Treatment, and
      Outcomes.
AB  - PURPOSE: The majority of new diagnoses of pediatric cancer are made in resource
      poor countries, where survival rates range from 5% to 25% compared with 80% in
      high-resource countries. Multiple factors, including diagnostic and treatment
      capacities and complex socioeconomic factors, contribute to this variation. This
      study evaluated the available resources and outcomes for pediatric patients with
      cancer at the first oncology treatment center in northern Tanzania. METHODS:
      Qualitative interviews were completed from July to August 2015 to determine
      available staff, hospital, diagnostic, treatment, and supportive care resources.
      A retrospective review of hospital admissions and clinic visits from January 2010
      to August 2014 was completed. A total of 298 patients were identified, and data
      from 182 patient files were included in this review. RESULTS: Diagnostic,
      treatment, and supportive capacities are limited for pediatric cancer care. The
      most common diagnoses were Burkitt lymphoma (n = 32), other non-Hodgkin lymphoma
      (n = 26), and Wilms tumor (n = 25). A total of 40% of patients (n = 72) abandoned
      care. There was a 20% 2-year event-free survival rate, which was significantly
      affected by patient age, method of diagnosis, and year of diagnosis. CONCLUSION:
      To our knowledge, this is the first review of pediatric cancer outcomes in
      northern Tanzania. The study identified areas for future development to improve
      pediatric cancer outcomes, which included strengthening of training and
      diagnostic capacities, development of registries and research databases, and the
      need for additional research to reduce treatment abandonment.

PMID- 30241178
TI  - Thyroid Cancer Incidences From Selected South America Population-Based Cancer
      Registries: An Age-Period-Cohort Study.
AB  - PURPOSE: The incidence of thyroid cancer (TC) has increased substantially
      worldwide. However, there is a lack of knowledge about age-period-cohort (APC)
      effects on incidence rates in South American countries. This study describes the
      TC incidence trends and analyzes APC effects in Cali, Colombia; Costa Rica;
      Goiania, Brazil; and Quito, Ecuador. MATERIALS AND METHODS: Data were obtained
      from the Cancer Incidence in Five Continents series, and the crude and age
      standardized incidence rates were calculated. Trends were assessed using the
      estimated annual percentage change, and APC models were estimated using Poisson
      regression for individuals between age 20 and 79 years. RESULTS: An increasing
      trend in age-standardized incidence rates was observed among women from Goiania
      (9.2%), Costa Rica (5.7%), Quito (4.0%), and Cali (3.4%), and in men from Goiania
      (10.0%) and Costa Rica (3.4%). The APC modeling showed that there was a period
      effect in all regions and for both sexes. Increasing rate ratios were observed
      among women over the periods. The best fit model was the APC model in women from
      all regions and in men from Quito, whereas the age-cohort model showed a better
      fit in men from Cali and Costa Rica, and the age-drift model showed a better fit
      among men from Goiania. CONCLUSION: These findings suggest that overdiagnosis is
      a possible explanation for the observed increasing pattern of TC incidence.
      However, some environmental exposures may also have contributed to the observed
      increase.

PMID- 30241179
TI  - Role of Granulocyte-Macrophage Colony-Stimulating Factor in Acute Myeloid
      Leukemia/Myelodysplastic Syndromes.
AB  - PURPOSE: Granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine
      stimulates growth, differentiation, and function of myeloid progenitors. We aimed
      to study the role of GM-CSF gene expression, its protein, and antibodies in
      patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) and
      their correlation to disease behavior and treatment outcome. The study included
      50 Egyptian patients with AML/MDS in addition to 20 healthy volunteers as control
      subjects. PATIENTS AND METHODS: Assessment of GM-CSF gene expression was
      performed by quantitative real-time polymerase chain reaction. GM-CSF proteins
      and antibodies were assessed by enzyme-linked immunosorbent assay. RESULTS: There
      was significant decrease in GM-CSF gene expression ( P = .008), increase in serum
      level of GM-CSF protein ( P = .0001), and increase in anti-GM-CSF antibodies ( P
      = .001) in patients with AML/MDS compared with healthy control subjects. In
      addition, there was a significant negative correlation between serum levels of GM
      CSF protein and initial peripheral blood blasts, percentage as well as response
      to therapy. CONCLUSION: Any alteration in GM-CSF gene expression could have
      implications in leukemogenesis. In addition, GM-CSF protein serum levels could be
      used to predict outcome of therapy. GM-CSF antibodies may also play a role in the
      pathogenesis of AML/MDS. The use of these GM-CSF parameters for disease
      monitoring and as markers of disease activity needs further research.

PMID- 30241181
TI  - Metastatic Lung Adenocarcinoma Harboring an EGFR-Activating Mutation in a Heart
      Transplant Recipient.

PMID- 30241180
TI  - Hematopoietic Stem-Cell Transplantation in the Resource-Limited Setting:
      Establishing the First Bone Marrow Transplantation Unit in Bangladesh.
AB  - PURPOSE: Treatment of malignant and nonmalignant hematologic diseases with
      hematopoietic stem-cell transplantation (HSCT) was first described almost 60
      years ago, and its use has expanded significantly over the last 20 years. Whereas
      HSCT has become the standard of care for many patients in developed countries,
      the significant economic investment, infrastructure, and health care provider
      training that are required to provide such a service have prohibited it from
      being widely adopted, particularly in developing countries. METHODS: Over the
      past two decades, however, efforts to bring HSCT to the developing world have
      increased, and several institutions have described their efforts to establish
      such a program. We aim to provide an overview of the current challenges and
      applications of HSCT in developing countries as well as to describe our
      experience in developing an HSCT program at Dhaka Medical College and Hospital in
      Bangladesh via a partnership with health care providers at Massachusetts General
      Hospital. RESULTS AND CONCLUSION: We discuss key steps of the program, including
      the formation of a collaborative partnership, infrastructure development, human
      resource capacity building, and financial considerations.

PMID- 30241182
TI  - Efficacy and Safety of Docetaxel in Elderly Patients With Metastatic Castration
      Resistant Prostate Cancer.
AB  - PURPOSE: Limited data are available about the tolerability and clinical outcomes
      of elderly patients with metastatic castration-resistant prostate cancer (mCRPC)
      who are treated with docetaxel. We evaluated the efficacy and safety of docetaxel
      as first-line chemotherapy for patients with mCRPC who were treated in our
      institution. MATERIALS AND METHODS: We retrospectively identified patients with
      mCRPC and a Karnosfky performance status of 60% or greater treated with docetaxel
      on any schedule as first-line chemotherapy between 2008 and 2013. The primary end
      point was a comparison of median overall survival (OS) according to age in this
      population. Secondary end points were comparisons of the rates of severe
      toxicities, prostate-specific antigen (PSA) decline of 50% or greater, and time
      to progression (TTP). Results were stratified by three age groups: younger than
      65 years, 65 to 74 years, and 75 years or older. RESULTS: Among the 197 patients
      included, 68 (34%) were younger than 65 years, 85 (43%) were 65 to 74 years, and
      44 (22%) were 75 years or older. The mean number of comorbidities was not
      different among groups (1.19 v 1.32 v 1.43; P = .54). Patients younger than 65
      years received a higher cumulative dose of docetaxel (450 mg/m2 v 382 mg/m2 v 300
      mg/m2; P = .004). The rates of PSA decline of 50% or greater (41% v 47% v 36.4%;
      P = .51) and the median TTP (5.13 v 5.13 v 4.7 months; P = .15) were comparable
      among all groups. The median OS was longer in the group of patients younger than
      age 65 years (19.6 v 12.4 v 12.3 months; P = .012). Rates of any grade 3 or
      higher adverse event were not different among groups (63.2% v 71.8% v 54.5%; P =
      .14). CONCLUSION: Administration of docetaxel in elderly patients who had good
      performance status was well tolerated. Rates of PSA decline and TTP were similar
      to those of younger patients, but median survival was lower.

PMID- 30241183
TI  - Shared Decision-Making in Patients With Prostate Cancer in Japan: Patient
      Preferences Versus Physician Perceptions.
AB  - This article adds the Japanese perspective to our knowledge of shared decision
      making (SDM) preferences by surveying patients with prostate cancer (PCA) and
      physicians in Japan. In 2015, 103 Japanese patients with PCA were asked about
      their SDM preferences by using an Internet-based 5-point-scale questionnaire.
      Concurrently, 127 Japanese physicians were surveyed regarding their perceptions
      of patient preferences on SDM. Drivers of preferences and perceptions were
      analyzed using univariable ordinal logistic regression and graphing the fitted
      response probabilities. Although 41% of both patients and physicians expressed
      and expected a desire for active involvement in treatment decisions (a higher
      rate than in a similar study for the United States in 2001), almost half the
      Japanese patients preferred SDM, but only 33% of physicians assumed this was
      their choice. That is, 29% of Japanese physicians underestimated patients'
      preference for involvement in making treatment decisions. Patients with lower
      health-related quality of life (as measured by the Functional Assessment of
      Cancer Therapy-Prostate [FACT-P]) expressed a stronger preference for SDM. The
      study shows that the worse the medical situation, the more patients with PCA
      prefer to be involved in the treatment decision, yet physicians tend to
      underestimate the preferences of their patients. Perhaps in contrast to common
      assumptions, Japanese patients are as interested in being involved in decision
      making as are patients in the United States.

PMID- 30241184
TI  - Comparison of Receptor-Defined Breast Cancer Subtypes Between German and Sudanese
      Women: A Facility-Based Cohort Study.
AB  - PURPOSE: The objective of this study was to compare tumor characteristics,
      biomarkers, and surrogate subtypes of breast cancer between Sudanese and German
      women. METHODS: Tumor characteristics and immunohistochemistry markers (estrogen
      receptor [ER], progesterone receptor [PR], and human epidermal growth factor
      receptor 2 [HER2]) were collected from the routine assessment of consecutive
      patients with invasive breast cancer diagnosed from 2010 to 2015 (Gezira
      University Pathology Laboratory, Gezira, Sudan) and from 1999 to 2013 (Breast
      Centre, Martin-Luther-University, Halle, Germany). RESULTS: A total of 2,492
      patients (German [n = 1,932] and Sudanese [n = 560]) were included. Age at
      diagnosis ranged from 20 to 94 years. Sudanese women were, on average, 10 years
      younger than German women, with a mean (+/- standard deviation) age of 48.8
      (13.5) and 58.6 (12.4) years, respectively. The Sudanese women had a higher
      grade, larger tumor, and more lymph node positivity compared with German women.
      ER-, PR-, and HER2-negative proportions were 55%, 61.8%, and 71.3%, respectively,
      for Sudanese women versus 22.7%, 32.3%, and 82.5%, respectively, for German
      women. The triple-negative subtype was more prevalent in Sudanese women (34.5%)
      than in German women (14.2%). The strongest factor associated with ER-negative
      disease was grade III (odds ratio, 19.6; 95% CI 11.6 to 33.4; P < .001). Sudanese
      patients were at higher risk for ER-negative breast cancer, with an odds ratio of
      2.01 ( P = .001; adjusted for age, size, nodal status, histologic type, and
      grade). Stratified by grade, the influence of origin was observed in grade I and
      grade II tumors, but not in grade III tumors. CONCLUSION: Sudanese women had more
      aggressive tumor characteristics and unfavorable prognostic biomarkers. After
      adjustment, Sudanese origin was still associated with hormone receptor-negative
      disease, especially in grade I and II tumors. These findings suggest differences
      in tumor biology among these ethnic groups.

PMID- 30241186
TI  - Chemoradiation and the Role of Adjuvant Chemotherapy in Lymph Nodal-Metastatic
      Cervical Cancer.
AB  - PURPOSE: To report the long-term outcome in lymph nodal-metastatic cervical
      squamous cell cancer after chemoradiation followed by adjuvant chemotherapy.
      PATIENTS AND METHODS: Between 2010 and 2013, five patients were diagnosed with
      advanced cervical cancer with clinically involved para-aortic lymph nodes (ie,
      International Federation of Gynecology and Obstetrics stage IVB). These patients
      were treated with concurrent chemoradiation therapy followed by adjuvant
      chemotherapy. Concurrent chemoradiation consisted of cisplatin given once per
      week concomitantly with extended-field radiation therapy followed by high-dose
      rate brachytherapy. Adjuvant chemotherapy comprised four courses of carboplatin
      and paclitaxel given every three weeks. The primary outcomes were local and
      distant failures. RESULTS: None of the patients had local recurrence or distal
      failure after a minimum follow-up time of 3 years. CONCLUSION: Adjuvant
      chemotherapy after chemoradiation has a probable role in the management of lymph
      nodal-metastatic cervical cancer.

PMID- 30241187
TI  - American Society of Clinical Oncology's Global Oncology Leadership Task Force:
      Findings and Actions.
AB  - In response to rising cancer incidence and mortality rates in low- and middle
      income countries and the increasingly global profile of ASCO's membership, the
      ASCO Board of Directors appointed the Global Oncology Leadership Task Force (Task
      Force) to provide recommendations on ASCO's engagement in global oncology. To
      accomplish its work, the Task Force convened meetings of global oncology experts,
      conducted focus group discussions with member groups, did site visits to South
      America and India, and met regularly to analyze the findings and develop
      recommendations. Task Force findings included global concerns, such as access to
      care, and specific concerns of middle- and low-resource settings. The need to
      strengthen health systems and the importance of alliances with a range of
      international cancer stakeholders were emphasized. Task Force recommendations to
      the ASCO Board of Directors were based on a three-part global oncology strategy
      of professional development, improvement of access to quality care, and
      acceleration of global oncology research. Specific areas of focus within each of
      these strategic pillars are provided along with an update on areas of ASCO
      activity as these recommendations are implemented.

PMID- 30241185
TI  - Breast Cancer and HIV in Sub-Saharan Africa: A Complex Relationship.
AB  - INTRODUCTION: The number and lifespan of individuals living with HIV have
      increased significantly with the scale-up of antiretroviral therapy. Furthermore,
      the incidence of breast cancer in women with HIV is growing, especially in sub
      Saharan Africa (SSA). However, the association between HIV infection and breast
      cancer is not well understood. METHODS: A literature search was performed to
      identify articles published in journals pertaining to breast cancer and HIV, with
      an emphasis on SSA. Selected US-based studies were also identified for
      comparison. RESULTS: Among the 56 studies reviewed, the largest study examined
      314 patients with breast cancer and HIV in the United States. There is no
      consensus on whether HIV infection acts as a pro-oncogenic or antioncogenic
      factor in breast cancer, and it may have no relation to breast cancer. A higher
      incidence of breast cancer is reported in high-income countries than in SSA,
      although breast cancer in SSA presents at a younger age and at a more advanced
      stage. Some studies show that patients with breast cancer and HIV experience
      worse chemotherapy toxicity than do patients without HIV. Data on treatment
      outcomes are limited. The largest study showed worse treatment outcomes in
      patients with HIV, compared with their counterparts without HIV. CONCLUSION: HIV
      infection has not been associated with different clinical presentation of breast
      cancer. However, some evidence suggests that concurrent diagnosis of HIV with
      breast cancer is associated with increased therapy-related toxicity and worse
      outcomes. Systematic prospective studies are needed to establish whether there is
      a specific association between breast cancer and HIV.

PMID- 30241188
TI  - Evidence on Effectiveness of Upper Neck Irradiation Versus Whole Neck Irradiation
      as Elective Neck Irradiation in Node-Negative Nasopharyngeal Cancer: A Meta
      Analysis.
AB  - PURPOSE: Nasopharyngeal carcinoma (NPC) is a central tumor with a rich lymphatic
      network and a propensity for bilateral cervical lymph node metastasis. There is
      an orderly pattern of lymph node involvement in NPC. There is no current standard
      for prophylactic neck irradiation in node-negative or limited retropharyngeal
      (RP) node-positive NPC. This study aims to synthesize the current evidence on
      upper neck irradiation (UNI) versus whole neck irradiation (WNI) as prophylactic
      neck irradiation in node-negative or limited RP node-positive NPC. MATERIALS AND
      METHODS: A search of relevant articles was done from 2000 to October 2015.
      Critical appraisal and meta-analysis of the eligible studies were undertaken to
      assess the effectiveness of UNI versus WNI as prophylactic neck irradiation in
      node-negative or limited involved RP node NPC. RESULTS: Only one randomized
      controlled trial investigated the use of prophylactic UNI versus WNI and showed
      no confirmed nodal relapse in both arms. Pooled analysis of four retrospective
      studies showed no significant difference in nodal recurrence, whether in-field or
      out-of-field recurrence. There was also no significant difference in terms of 5
      year distant metastasis-free and overall survival. CONCLUSION: In node-negative
      or limited RP node-positive NPC, the current evidence shows the possibility of
      treating only the upper neck (levels II, III, and VA) without compromising nodal
      control, distant metastasis, and overall survival. As a result of the scarcity of
      data, more randomized clinical trials are warranted in this subset of patients.

PMID- 30241189
TI  - Clinical Presentation and Gene Expression Profiling of Immunoglobulin M Multiple
      Myeloma Compared With Other Myeloma Subtypes and Waldenstrom Macroglobulinemia.
AB  - PURPOSE: Multiple myeloma (MM) is a clonal bone marrow disease characterized by
      the neoplastic transformation of differentiated postgerminal B cells. It is a
      heterogeneous disease both at the genetic level and in terms of clinical outcome.
      Immunoglobulin M (IgM) MM is a rare subtype of myeloma. Similar to Waldenstrom
      macroglobulinemia (WM), patients with MM experience IgM monoclonal gammopathy;
      however, both diseases are distinct in terms of treatment and clinical behavior.
      MATERIALS AND METHODS: To shed light on the presentation of IgM MM, its
      prognosis, and its gene expression profiling, we identified and characterized 21
      patients with IgM MM from our database. RESULTS: One of these patients presented
      with a rare IgM monoclonal gammopathy of undetermined significance that
      progressed to smoldering myeloma. The median survival of the 21 patients was 4.9
      years, which was comparable to a matched group of patients with non-IgM MM with
      similar myeloma prognostic factors (age, gender, albumin, creatinine, anemia,
      lactate dehydrogenase, beta2-microglobulin, cytogenetics abnormalities), but much
      less than the median survival reported for patients with WM (9 years). We
      identified a cluster of genes that differ in their expression profile between MM
      and WM and found that the patients with IgM MM displayed a gene expression
      profile most similar to patients with non-IgM MM, confirming that IgM MM is a
      subtype of MM that should be differentiated from WM. CONCLUSION: Because the
      prognosis of IgM MM and WM differ significantly, an accurate diagnosis is
      essential. Our gene expression model can assist with the differential diagnosis
      in controversial cases.

PMID- 30241190
TI  - Unfortunate Accident or Blessing in Disguise? Dramatic Response to Incidental
      Intrathoracic Delivery of Anti-HER2 Regimen.

PMID- 30241191
TI  - Anxiety- and Health-Related Quality of Life Among Patients With Breast Cancer: A
      Cross-Cultural Comparison of China and the United States.
AB  - PURPOSE: Literature has documented the prevalence of anxiety and its adverse
      effect on quality of life among patients with breast cancer from Western
      countries, yet cross-cultural examinations with non-Western patients are rare.
      This cross-cultural study investigated differences in anxiety and its association
      with quality of life between US and Chinese patients with breast cancer. METHODS:
      Patients with breast cancer from the United States and China completed measures
      for anxiety (Spielberger State-Trait Anxiety Inventory) and quality of life
      (Functional Assessment of Cancer Therapy-Breast). RESULTS: After controlling for
      demographic and medical characteristics, Chinese patients reported higher levels
      of trait and state anxiety than US patients. Although there was an association
      between anxiety and quality of life in both groups of patients, the association
      between state anxiety and quality of life was stronger among Chinese patients
      than among US patients, with the association between trait anxiety and quality of
      life the same between the two cultural samples. CONCLUSION: These findings
      suggest that anxiety and its association with quality of life among patients with
      breast cancer varies depending on cultural context, which reveals greater anxiety
      and poorer quality of life among Chinese patients compared with US patients. This
      suggests greater unmet psychosocial needs among Chinese patients and highlights
      the need to build comprehensive cancer care systems for a better quality of life
      in Chinese populations.

PMID- 30241194
TI  - Confession of a Pediatric Oncologist.

PMID- 30241192
TI  - Predictors and Prevalence of Pain and Its Management in Four Regional Cancer
      Hospitals in India.
AB  - PURPOSE: More than 1 million new occurrences of cancer are diagnosed in India
      annually. Among patients with cancer, pain is a common and persistent symptom of
      the disease and its treatment. However, few studies to date have evaluated the
      prevalence of pain and the adequacy of pain management in Indian hospitals. This
      cross-sectional study aimed to assess the prevalence and sociodemographic
      patterns of cancer pain and pain management among a sample of inpatients and
      newly registered outpatients at four large regional cancer centers in India.
      METHODS: A sample of 1,600 patients with cancer who were current inpatients or
      newly registered outpatients were recruited and administered a questionnaire that
      was based on the Brief Pain Inventory. The survey tool included questions on
      demographics, medical history, and extent of clinical pain experienced. In
      addition, a pain management index score was created to link the severity of
      cancer pain with medication prescribed to treat it. RESULTS: A total of 88% of
      patients reported pain in the past 7 days, and approximately 60% reported that
      their worst pain was severe. Several demographic and medical characteristics of
      the study population predicted severe pain, including the following: lower
      educational level, outpatient status, and debt incurred as a result of illness. A
      total of 67% of patients were inadequately treated with analgesics. Inadequate
      pain management was associated with both treatment hospital and patient type, and
      patients who reported debt as a result of their illness were more likely to have
      inadequate pain management. CONCLUSION: A majority of Indian patients with cancer
      experience significant pain and receive inadequate pain management. Improvement
      of pain management for Indian patients with cancer is needed urgently.

PMID- 30241193
TI  - Evolving Treatment Paradigms for Oropharyngeal Squamous Cell Carcinoma.
AB  - Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence in the
      United States and in many countries worldwide primarily as a result of increasing
      rates of human papillomavirus (HPV) infection. HPV-positive OPSCC represents a
      distinct disease entity from head and neck squamous cell carcinoma caused by
      traditional risk factors such as tobacco and alcohol, with different
      epidemiology, patterns of failure, and expected outcomes. Because patients with
      HPV-positive OPSCC have a younger median age and superior prognosis compared with
      their HPV-negative counterparts, they live longer with the morbidity of
      treatment, which can be severe. Therefore, efforts are under way to de-escalate
      therapy in favorable-risk patients while maintaining treatment efficacy.
      Additional work is being undertaken to discover new therapies that may benefit
      both HPV-positive and HPV-negative patient subsets. Herein, we will review the
      available data for the evolving treatment paradigms in OPSCC as well as discuss
      ongoing clinical trials.

PMID- 30241195
TI  - Case Report of a Pregnancy During Ipilimumab Therapy.

PMID- 30241196
TI  - Oncology in Iraq's Kurdish Region: Navigating Cancer, War, and Displacement.

PMID- 30241197
TI  - Imatinib-Associated Tumor Lysis Syndrome in a Patient With Myeloid Neoplasm With
      Eosinophilia and PDGFRA Rearrangement: A Case Report and Review of the
      Literature.

PMID- 30241198
TI  - Retrospective Clinical Study of Advanced Pancreatic Cancer Treated With
      Chemotherapy and Abdominal Hyperthermia.
AB  - PURPOSE: Hyperthermia is a mechanistically plausible partner with chemotherapy,
      although many of the underlying molecular mechanisms of this combination
      treatment are not yet properly understood. Preclinical studies suggest that there
      is potential synergy with gemcitabine and that provides the basis for
      retrospective analysis of a clinical series combining these treatment modalities
      for patients with advanced pancreatic cancer. PATIENTS AND METHODS: Twenty-nine
      chemotherapy-naive patients with locally advanced or metastatic pancreatic
      carcinoma with malignant ascites were treated with intraperitoneal cisplatin 30
      mg/m2 and gemcitabine 800 to 1,000 mg/m2 intravenously on days 1, 8, and 15 every
      28 days until tumor progression. Patients also received regional hyperthermia
      treatment (41 to 42 degrees C) on the upper abdomen two times per week from days
      1 to 21. RESULTS: In all, 83 cycles of chemotherapy were administered and were
      generally well tolerated. No patients had a complete response, 13 had a partial
      response, seven had stable disease, and 9 had progressive disease. Mean
      progression-free survival and overall survival were 119 +/- 61days and 195 +/- 98
      days, respectively. CONCLUSION: This study provides preliminary evidence that the
      treatment approach of combined systemic and intraperitoneal chemotherapy plus
      hyperthermia is well tolerated, is active, and has an acceptable survival profile
      for patients with stage IV pancreatic cancer and ascites.

PMID- 30241199
TI  - International Analysis of Age-Specific Mortality Rates From Mesothelioma on the
      Basis of the International Classification of Diseases, 10th Revision.
AB  - Past analyses of mortality data from mesothelioma relied on unspecific codes,
      such as pleural neoplasms. We calculated temporal trends in age-specific
      mortality rates in Canada, the United States, Japan, France, Germany, Italy, the
      Netherlands, Poland, the United Kingdom, and Australia on the basis of the 10th
      version of the International Classification of Diseases, which includes a
      specific code for mesothelioma. Older age groups showed an increase (in the
      United States, a weaker decrease) during the study period, whereas in young age
      groups, there was a decrease (in Poland, a weaker increase, starting, however,
      from low rates). Results were consistent between men and women and between
      pleural and peritoneal mesothelioma, although a smaller number of events in women
      and for peritoneal mesothelioma resulted in less precise results. The results
      show the heterogeneous effect of the reduction of asbestos exposure on different
      age groups; decreasing mortality in young people reflects reduced exposure
      opportunity, and increasing mortality in the elderly shows the long-term effect
      of early exposures.

PMID- 30241200
TI  - Improving Access to Cancer Testing and Treatment in Kenya.
AB  - PURPOSE: In response to the increasing cancer burden in Kenya, this study
      identified barriers to patients seeking access to cancer testing and treatment
      and to clinicians in delivering these services. Policy recommendations based on
      findings are presented. METHODS: This qualitative study used semistructured key
      informant interviews. Purposive sampling was used to recruit 14 participants:
      seven oncology clinicians and seven support and advocacy leaders for patients
      with cancer. Qualitative analysis was used to identify themes. RESULTS: Seven
      barriers to cancer testing and treatment were identified: high cost of testing
      and treatment, low level of knowledge about cancer among population and
      clinicians, poor health-seeking behaviors among population, long distances to
      access diagnostic and treatment services, lack of decentralized diagnostic and
      treatment facilities, poor communication, and lack of better cancer policy
      development and implementation. CONCLUSION: Kenyans seeking cancer services face
      significant barriers that result in late presentation, misdiagnosis, interrupted
      treatment, stigma, and fear. Four policy recommendations to improve access for
      patients with cancer are (1) improve health insurance for patients with cancer;
      (2) establish testing and treatment facilities in all counties; (3) acquire
      diagnosis and treatment equipment and train health personnel to screen, diagnose,
      and treat cancer; and (4) increase public health awareness and education about
      cancer to improve diagnoses and treatment. Effective cancer testing and treatment
      options can be developed to address cancer in a resource-constrained environment
      like Kenya. An in-depth look at effective interventions and policies being
      implemented in countries facing similar challenges would provide valuable lessons
      to Kenya's health sector and policymakers.

PMID- 30241201
TI  - Can Radiotherapy Be Omitted in Children With Hodgkin Lymphoma Who Achieve
      Metabolic Remission on Interim Positron Emission Tomography? Experience of a
      Tertiary Care Cancer Referral Center.
AB  - PURPOSE: Treating pediatric Hodgkin lymphoma (HL) involves a delicate balance
      between cure and reducing late toxicity. Fluorodeoxyglucose positron emission
      tomography (PET) combined with computed tomography (CT) identifies patients with
      early response to chemotherapy, for whom radiotherapy may be avoided. The role of
      PET-CT in upfront risk stratification and response-adapted treatment is evaluated
      in this study. METHODS: Patients with HL, who were younger than 18 years, were
      included. PET-CT was performed at baseline and after two cycles of chemotherapy.
      Patients were stratified into three risk groups: group 1 (stage I or II with no
      unfavorable features); group 2 (stage I or II with bulky disease/B symptoms); and
      group 3 (stage III/IV). A doxorubicin, bleomycin, vinblastine, dacarbazine-based
      regimen was used in early disease. A cyclophosphamide, vincristine, prednisolone,
      procarbazine, doxorubicin, bleomycin, vinblastine-based regimen was used in
      advanced disease. RESULTS: Forty-nine patients were included. Fifteen (31%),
      seven (14%), and 27 (55%) patients were included in groups 1, 2, and 3,
      respectively. Among 36 patients who underwent staging by PET-CT at diagnosis,
      seven (19%) patients were upstaged and one (3%) patient was downstaged by PET
      compared with CT. On the basis of negative interim PET responses, 39 (80%)
      patients were treated without radiotherapy. The 3-year event-free survival for
      the entire cohort was 91% (+/- 5.2%) and overall survival was 100%. CONCLUSION:
      PET-CT is an excellent stand-alone staging modality in HL. The omission of
      radiotherapy can be considered in patients who achieve metabolic remission on
      interim PET.

PMID- 30241202
TI  - Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer: A
      Retrospective Analysis.
AB  - PURPOSE: Extensive-stage small-cell lung cancer (esSCLC) is an incurable disease
      and represents a therapeutic challenge because of its poor prognosis. Studies in
      prophylactic cranial irradiation (PCI) in esSCLC have shown a decreased incidence
      of symptomatic brain metastases in patients who respond to systemic chemotherapy.
      However, its effect on overall survival is debatable. We evaluated the benefit of
      PCI in patients with esSCLC in terms of overall survival, progression-free
      survival, incidence of brain metastases, recurrence rate, and exposure to
      postrecurrence therapies. MATERIALS AND METHODS: We retrospectively reviewed
      electronic charts from patients diagnosed with esSCLC from 2008 to 2014 at our
      institution. All patients had negative baseline brain imaging before chemotherapy
      and PCI and received at least 4 cycles of platinum-based chemotherapy in the
      first-line setting without progressive disease on follow-up. PCI was performed at
      the discretion of the treating physician. Analyses were based on descriptive
      statistics. Survival curves were calculated by Kaplan-Meier method. RESULTS:
      Among 46 eligible patients, 16 (35%) received PCI and 30 (65%) did not. Compared
      with no PCI, PCI led to improved progression-free survival (median, 10.32 v 7.66
      months; hazard ratio, 0.4521; 95% CI, 0.2481 to 0.8237; P < .001) and overall
      survival (median, 20.94 v 11.05 months; hazard ratio, 0.2655; 95% CI, 0.1420 to
      0.4964; P < .001) as well as lower incidence of brain metastases (19% v 53%; P =
      .0273) and higher exposure to second-line chemotherapy (87% v 57%; P = .0479).
      CONCLUSION: Careful patient selection for PCI can improve not only brain
      metastases control and higher second-line chemotherapy exposure but also patient
      survival.

PMID- 30241204
TI  - Video-Teleconferencing in Pediatric Neuro-Oncology: Ten Years of Experience.
AB  - PURPOSE: The management of central nervous system tumors is challenging in low-
      and middle-income countries. Little is known about applicability of twinning
      initiatives with high-income countries in neuro-oncology. In 2004, a monthly
      neuro-oncology video-teleconference program was started between King Hussein
      Cancer Center (Amman, Jordan) and the Hospital for Sick Children (Toronto,
      Ontario, Canada). More than 100 conferences were held and > 400 cases were
      discussed. The aim of this work was to assess the sustainability of such an
      initiative and the evolution of the impact over time. METHODS: We divided the
      duration in to three eras according to the initial 2 to 3 years of work of three
      consecutive oncologists in charge of the neuro-oncology program at King Hussein
      Cancer Center. We retrospectively reviewed the written minutes and compared the
      preconference suggested plans with the postconference recommendations. Impact of
      changes on the patient care was recorded. RESULTS: Thirty-three sets of written
      minutes (covering 161 cases) in the middle era and 32 sets of written minutes
      (covering 122 cases) in the last era were compared with the initial experience
      (20 meetings, 72 cases). Running costs of these conferences has dropped from
      $360/h to < $40/h. Important concepts were introduced, such as multidisciplinary
      teamwork, second-look surgery, and early referral. Suggestions for plan changes
      have decreased from 44% to 30% and 24% in the respective consecutive eras. Most
      recommendations involved alternative intervention modalities or pathology review.
      Most of these recommendations were followed. CONCLUSION: Video-teleconferencing
      in neuro-oncology is feasible and sustainable. With time, team experience is
      built while the percentage and the type of treatment modifications change.
      Commitment and motivation helped maintain this initiative rather than
      availability of financial resources. Improvement in patients' care was achieved,
      in particular, with the implementation of a multidisciplinary team and the
      continuous effort to implement recommendations.

PMID- 30241205
TI  - Palliative Care Development in Africa: Lessons From Uganda and Kenya.
AB  - PURPOSE: Despite increased access to palliative care in Africa, there remains
      substantial unmet need. We examined the impact of approaches to promoting the
      development of palliative care in two African countries, Uganda and Kenya, and
      considered how these and other strategies could be applied more broadly. METHODS:
      This study reviews published data on development approaches to palliative care in
      Uganda and Kenya across five domains: education and training, access to opioids,
      public and professional attitudes, integration into national health systems, and
      research. These countries were chosen because they are African leaders in
      palliative care, in which successful approaches to palliative care development
      have been used. RESULTS: Both countries have implemented strategies across all
      five domains to develop palliative care. In both countries, successes in these
      endeavors seem to be related to efforts to integrate palliative care into the
      national health system and educational curricula, the training of health care
      providers in opioid treatment, and the inclusion of community providers in
      palliative care planning and implementation. Research in palliative care is the
      least well-developed domain in both countries. CONCLUSION: A multidimensional
      approach to development of palliative care across all domains, with concerted
      action at the policy, provider, and community level, can improve access to
      palliative care in African countries.

PMID- 30241206
TI  - Triage of Women Testing Positive With the careHPV Test on Self-Collected Vaginal
      Samples for Cervical Cancer Screening in a Low-Resource Setting.
AB  - PURPOSE: Human papillomavirus (HPV) DNA screening reduces cervical cancer
      incidence and mortality in low-resource settings. Self-collected vaginal samples
      tested with affordable HPV tests such as careHPV can increase the rate of
      screening in resource-constrained settings. We report the role of visual
      inspection with acetic acid (VIA) as a triage test for women testing positive
      with the careHPV test on self-collected vaginal samples. METHODS: As part of a
      multicountry demonstration study, 5,207 women 30 to 49 years of age were
      recruited from urban slums to undergo four cervical screening tests using the
      careHPV test on self-collected vaginal samples, provider-collected cervical
      samples, the Papanicolaou test, and VIA. All women who tested positive for any of
      the screening tests were evaluated with colposcopy and guided biopsies, followed
      by treatment if any cervical lesions were detected. The data from the 377 women
      who tested positive for HPV in the self-collected vaginal samples were also
      analyzed to assess the performance of VIA, conventional cytology, and colposcopy,
      as triage tests in the detection of cervical cancer and precancerous lesions.
      RESULTS: Nineteen percent of women who tested positive for vaginal HPV (V-HPV)
      also tested positive with the VIA test; cervical intraepithelial neoplasia 2+
      lesions were detected in 58% of these women. In the 30 % of the women who tested
      positive for V-HPV with cytology triage, cervical intraepithelial neoplasia 2+
      lesions were detected in 80% of these women. The colposcopy referrals for women
      who tested positive for V-HPV were reduced from 7.6% to 1.5% by VIA triage, and
      to 2.3% by cytology triage. Although the sensitivity was reduced, the positive
      predictive value improved after triage with VIA and cytology. CONCLUSION: This
      study reflects the optimal role of VIA triaging for treatment selection of
      lesions among those who test positive for V-HPV in screen and treat screening
      programs that use an HPV test in low-resource settings.

PMID- 30241208
TI  - Acknowledgment of Reviewers, 2017.

PMID- 30241207
TI  - Quality of Breast Cancer Treatment at a Rural Cancer Center in Rwanda.
AB  - PURPOSE: As breast cancer incidence and mortality rise in sub-Saharan Africa, it
      is critical to identify strategies for delivery of high-quality breast cancer
      care in settings with limited resources and few oncology specialists. We
      investigated the quality of treatments received by a cohort of patients with
      breast cancer at Butaro Cancer Center of Excellence (BCCOE), Rwanda's first
      public cancer center. PATIENTS AND METHODS: We reviewed medical records of all
      female patients diagnosed with invasive breast cancer at BCCOE between July 2012
      and December 2013. We evaluated the provision of chemotherapy, endocrine therapy,
      surgery, and chemotherapy dose densities. We also applied modified international
      quality metrics and estimated overall survival using interval-censored analysis.
      RESULTS: Among 150 patients, 28 presented with early-stage, 64 with locally
      advanced, and 53 with metastatic disease. Among potentially curable patients (ie,
      those with early-stage or locally advanced disease), 74% received at least four
      cycles of chemotherapy and 63% received surgery. Among hormone receptor-positive
      patients, 83% received endocrine therapy within 1 year of diagnosis. Fifty-seven
      percent of potentially curable patients completed surgery and chemotherapy and
      initiated endocrine therapy if indicated within 1 year of biopsy. Radiotherapy
      was not available. At the end of follow-up, 62% of potentially curable patients
      were alive, 24% were dead, and 14% were lost to follow-up. CONCLUSION:
      Appropriate delivery of chemotherapy and endocrine therapy for breast cancer is
      possible in rural sub-Saharan African even without oncologists based on site.
      Performing timely surgery and ensuring treatment completion were key challenges
      after the opening of BCCOE. Further investigation should examine persistent
      quality gaps and the relationship between treatment quality and survival.

PMID- 30241209
TI  - Chasing the Cure Around the Globe: Medical Tourism for Cancer Care From
      Developing Countries.

PMID- 30241210
TI  - Breast Cancer Staging: Is TNM Ready to Evolve?

PMID- 30241203
TI  - Survey of Third-Party Parenting Options Associated With Fertility Preservation
      Available to Patients With Cancer Around the Globe.
AB  - PURPOSE: In the accompanying article, "Analysis of Fertility Preservation Options
      Available to Patients With Cancer Around the Globe," we showed that specific
      fertility preservation services may not be offered at various sites around the
      world because of cultural and legal barriers. We assessed global and regional
      experiences as well as the legal status of third-party reproduction and adoption
      to serve as a comprehensive international data set and resource for groups that
      wish to begin oncofertility interventions. METHODS: We provide data on the
      legalities of third-party assisted reproductive technologies and other family
      building options in the 28 oncofertility-practicing countries surveyed. RESULTS:
      We found regional and country differences that will be important in the
      development of tailored resources for physicians and for patient brochures that
      are sensitive to these local restrictions and cultural norms. CONCLUSION: Because
      many patients first consult Web-based materials, the formal assessment of the
      availability of these options provides members of the global oncofertility
      community with data to which they might otherwise not have ready access to better
      serve their patients.

PMID- 30241211
TI  - Molecular Diagnostics for AIDS Lymphoma Diagnosis in South Africa and the
      Potential for Other Low- and Middle-Income Countries.

PMID- 30241212
TI  - Frequency of BRAF V600E Mutation in the Mexican Population of Patients With
      Metastatic Melanoma.
AB  - PURPOSE: The BRAF V600E mutation has been described in melanomas occurring in the
      Caucasian, European, and Asian populations. However, in the Mexican population,
      the status and clinical significance of BRAF mutation has not been researched on
      a large scale. METHODS: Consecutive BRAF-tested Mexican patients with metastatic
      melanoma (n = 127) were analyzed for mutations in exon 15 of the BRAF gene in
      genomic DNA by real-time polymerase chain reaction technology for amplification
      and detection. The results were correlated with the clinical-pathologic features
      and the prognosis of the patients. RESULTS: The frequency of somatic mutation
      V600E within the BRAF gene was 54.6% (43 of 127 patients). Nodular melanoma was
      the most prevalent subtype in our population, with BRAF mutations in 37.2% (16 of
      55 patients). In contrast, superficial spread had a frequency of 18.6% BRAF
      mutation (eight of 24). Other clinicopathologic features were assessed to
      correlate with the mutation status. CONCLUSION: This study searched for the most
      prevalent BRAF V600E mutation type in melanoma in a heterogeneous population from
      Mexico. Nodular melanoma was found to be the most prevalent in metastatic
      presentation and the presence of BRAF V600E mutation, perhaps related to the
      mixed ancestry; in the north, ancestry is predominantly European and in the
      south, it is predominantly Asian. The outcomes of the mutation correlations were
      similar to those found in other populations.

PMID- 30241213
TI  - Screening for Lung Cancer Has Limited Effectiveness Globally and Distracts From
      Much Needed Efforts to Reduce the Critical Worldwide Prevalence of Smoking and
      Related Morbidity and Mortality.

PMID- 30241214
TI  - Interfraction Variation and Dosimetric Changes in Patients With Cervical Cancer
      Treated With Intracavitary Brachytherapy.
AB  - PURPOSE: Intracavitary brachytherapy is integral in the treatment of cervical
      cancer. Because of interfraction variation, the current standard is replanning
      with every fraction. This study aimed to determine whether there was a difference
      in relative dosimetry if the source position and dwell time of the first fraction
      were applied to subsequent fractions. MATERIALS AND METHODS: The authors
      performed a retrospective review of charts and films from 2007 to 2012. Eligible
      cases were patients with cervical cancer treated with brachytherapy with the same
      dose prescription to point A. Replanning was done on the first set of orthogonal
      plates. Source position and dwell time were subsequently applied to the remaining
      fractions using actual films. RESULTS: Twenty-nine patients were included in this
      study. The results showed that cervical, rectal, and bladder dose between the
      actual plan and the hypothetical plan were not statistically different. In the
      hypothetical plan, the source activity and dwell time of the first plan were
      applied to the orthogonal films of the subsequent fractions and showed no
      significant difference in all dose points. CONCLUSION: The results of this study
      showed proof of concept of the safety of using the source position and dwell time
      of the first plan for subsequent fractions. Until further studies are performed
      (also using three-dimensional planning software), the concept should be
      considered investigational because of the small sample size of the study. Until
      such research is performed, it is still strongly recommended that replanning be
      performed with every fraction whenever it is feasible.

PMID- 30241215
TI  - Building a Network of Health Professionals for Breast and Cervical Cancer Control
      in the Andean Region.
AB  - PURPOSE: Cancer mortality is approximately twice as high in Latin American
      countries than in more developed countries. In particular, the countries of the
      high Andean region of Latin America carry a double burden of breast and cervical
      cancers. In these countries, there are disproportionately higher mortality to
      incidence ratios compared with other regions in Latin America. The US National
      Cancer Institute's Center for Global Health, the Pan American Health
      Organization, and the Ministry of Health in Peru collaborated to design and
      execute an education and advocacy workshop in Lima, Peru. The workshop was
      convened to discuss regional challenges and practices, as well as to support the
      implementation of Plan Esperanza, Peru's national cancer control plan. METHODS:
      Workshop participants included local and international experts to present the
      state of the science, health practitioners, and advocacy groups to discuss unique
      barriers that women in the region experience. RESULTS: Inequalities in access to
      and distribution of medical expertise, lack of continuity of cancer control
      plans, and the need for sustained public buy-in emerged as obstacles. CONCLUSION:
      The workshop provided a forum to discuss key issues regarding breast and cervical
      cancer control among health professionals and advocates in Peru and the region.
      This article outlines the resulting recommendations.

PMID- 30241217
TI  - Going the Distance: Ethical Issues Arising When Patients Seek Cancer Care From
      International Settings.

PMID- 30241216
TI  - Reply to M. Swanson et al.

PMID- 30241218
TI  - Peliosis Hepatis Simulates Liver Metastases.

PMID- 30241219
TI  - Cost of Providing Quality Cancer Care at the Butaro Cancer Center of Excellence
      in Rwanda.
AB  - PURPOSE: The cost of providing cancer care in low-income countries remains
      largely unknown, which creates a significant barrier to effective planning and
      resource allocation. This study examines the cost of providing comprehensive
      cancer care at the Butaro Cancer Center of Excellence (BCCOE) in Rwanda. METHODS:
      A retrospective costing analysis was conducted from the provider perspective by
      using secondary data from the administrative systems of the BCCOE. We identified
      the start-up funds necessary to begin initial implementation and determined the
      fiscal year 2013-2014 operating cost of the cancer program, including capital
      expenditures and fixed and variable costs. RESULTS: A total of $556,105 US
      dollars was assessed as necessary start-up funding to implement the program. The
      annual operating cost of the cancer program was found to be $957,203 US dollars.
      Radiotherapy, labor, and chemotherapy were the most significant cost drivers.
      Radiotherapy services, which require sending patients out of country because
      there are no radiation units in Rwanda, comprised 25% of program costs, labor
      accounted for 21%, and chemotherapy, supportive medications, and consumables
      accounted for 15%. Overhead, training, computed tomography scans, surgeries,
      blood products, pathology, and social services accounted for less than 10% of the
      total. CONCLUSION: This study is one of the first to examine operating costs for
      implementing a cancer center in a low-income country. Having a strong commitment
      to cancer care, adapting clinical protocols to the local setting, shifting tasks,
      and creating collaborative partnerships make it possible for BCCOE to provide
      quality cancer care at a fraction of the cost seen in middle- and high-income
      countries, which has saved many lives and improved survival. Not all therapies,
      though, were available because of limited financial resources.

PMID- 30241220
TI  - Incidence and Prevalence of Cancer in Colombia: The Methodology Used Matters.
AB  - PURPOSE: Incidence and prevalence are important factors in policy making and
      planning in health care systems. The aim of this study was to compare two
      different estimates of the incidence and prevalence of cancer in Colombia-real
      world data from the health care system and estimates from cancer registries.
      MATERIALS AND METHODS: Data from all providers were aggregated by the High-Cost
      Diseases Office (Cuenta de Alto Costo [CAC]). The real-world, age-standardized
      observed incidence (OI) and observed prevalence (OP) rates were calculated using
      the number of patients with a diagnosis of cancer who were cared for in the
      national health system between 2014 and 2015. The registry estimated incidence
      (EI) and estimated prevalence (EP) were extracted from GLOBOCAN population fact
      sheets for 2012, which use data from four Colombian city-based registries and
      extrapolate survival using the average for Asian countries, together with
      registries from Uganda and Zimbabwe. RESULTS: A total of 130,441 patients were
      analyzed. The OI of cancer in Colombia was 69.2 and the OP was 479 (per 100,000
      people) in early 2015, whereas the EI was 175.2 and the 5-year EP was 501.2 (per
      100,000 people), showing a higher estimate from GLOBOCAN data for 2012 than was
      observed in early 2015 by the CAC. Some differences were higher in specific
      cancers. CONCLUSION: Because of differences in methodology, the EI and the EP are
      not comparable to the OI and the OP. Policymakers need robust and current
      information to prioritize disease prevention and control programs. In Colombia,
      the OI and the OP-calculated by the CAC with data from the whole country-offer an
      opportunity for a more precise real-world estimation of patients with cancer in
      Colombia.

PMID- 30241221
TI  - Health-Related Quality of Life and Survival Outcomes of Pediatric Patients With
      Nonmetastatic Osteosarcoma Treated in Countries With Different Resources.
AB  - PURPOSE: Health-related quality of life (HRQOL) improves throughout treatment of
      patients with nonmetastatic osteosarcoma. We compared HRQOL for patients in the
      United States and Chile treated on an international trial (OS99) with
      polychemotherapy and surgery, and we assessed the relationships among HRQOL
      measures, event-free survival (EFS), and overall survival (OS). MATERIALS AND
      METHODS: Patients with newly diagnosed, localized osteosarcoma and their parents
      completed three HRQOL instruments (PedsQL v.4, PedsQL Cancer v.3, and Symptom
      Distress Scale [SDS]). Data were collected at four time points throughout
      therapy. Repeated measures models were used to investigate the effect of
      treatment site on instrument scores. The log-rank test examined the impact of
      treatment site on survival outcomes, and Cox proportional hazards regression
      models evaluated baseline HRQOL measures as predictors of EFS and OS. RESULTS: Of
      71 eligible patients, 66 (93%) participated in the HRQOL studies in the United
      States (n = 44) and Chile (n = 22). The median age was 13.4 years (range, 5 to 23
      years). Clinical characteristics were similar between treatment sites. US
      patients reported better scores for physical ( P = .030), emotional ( P = .027),
      and school functioning ( P < .001). Chilean patients reported poorer scores for
      worry ( P < .001) and nausea ( P = .007). Patient and parent nausea scores were
      similar between patients treated in the United States and Chile by the end of
      therapy. Differences in symptom distress were not observed between the countries.
      Neither HRQOL measures nor treatment site were associated with EFS or OS.
      CONCLUSION: Although significant differences in HRQOL were observed between
      countries, outcomes were similar, and HRQOL measures were not associated with
      prognosis.

PMID- 30241222
TI  - Characteristics of Esophageal Cancer Cases in Tanzania.
AB  - PURPOSE: Age-standardized incidence rates for esophageal cancer (EC) in East
      Africa have been reported as disproportionately high compared with the worldwide
      incidence of nine per 100,000 population. This study aimed to characterize EC
      cases seen at Muhimbili National Hospital and Ocean Road Cancer Institute in Dar
      es Salaam, Tanzania. METHODS: Demographic, clinical, and treatment variables were
      abstracted from charts of patients who received care for a diagnosis of EC at one
      or both institutions between 2011 and 2013. Categorical data were summarized as
      frequency counts and percentages. Continuous data were presented as medians and
      ranges. To compare men and women, Pearson's chi2 and two-sample t tests were
      applied. RESULTS: Seven hundred thirty-eight unique cases of EC were identified,
      of whom 68% were men and the median age was 60 years (range, 19 to 95 years).
      Notably, 93 cases (13%) were <= 40 years old at diagnosis. Squamous cell
      carcinoma was the dominant histology, comprising 90% of cases with documented
      histopathology. However, 34% of cases with a diagnosis of EC were not
      pathologically confirmed. The stage was documented as locoregional in 4% of
      cases, locally advanced in 20% of cases, metastatic in 14% of cases, and unknown
      in 63% of cases. Of 430 patients who received treatment at Ocean Road Cancer
      Institute, 76% were treated with radiation, 44% were treated with chemotherapy,
      3% underwent a cancer-related surgical procedure, and 10% of cases received no
      cancer-directed therapy. The median overall survival for all patients was 6.9
      months (95% CI, 5.0 to 12.8), regardless of stage at presentation. CONCLUSION:
      Between 2011 and 2013, cases of EC represented a large clinical burden at both
      institutions.

PMID- 30241223
TI  - Diagnostically Challenging Case: Metastatic Hepatocellular Carcinoma With No
      Liver Lesion at Imaging.

PMID- 30241224
TI  - Variation in Adherence Measures to Imatinib Therapy.
AB  - PURPOSE: The introduction of tyrosine kinase inhibitors has transformed the care
      of patients with chronic myeloid leukemia, with survival approaching that of
      healthy individuals. Current-day challenges in chronic myeloid leukemia care
      include adherence to tyrosine kinase inhibitor therapy. We studied adherence from
      resource-constrained settings and tried to analyze the factors responsible for
      nonadherence in these individuals. We also correlated adherence to current
      molecular status. PATIENTS AND METHODS: This was a single-center, cross
      sectional, observational study from north India. It consisted of a questionnaire
      based survey in which a one-to-one interview technique was used by trained
      nursing staff administering the Modified Morisky Adherence Scale (MMAS-9)
      questionnaire. Adherence was also measured on the basis of physician's
      assessment. JMP 13.0.0 was used for statistical analysis. RESULTS: A total of 333
      patients with a median age of 42 years were included in the study. The median BCR
      ABL/ABL ratio (IS) was 0.175 (0.0 to 98.0). The mean MMAS-9 score was 11 +/- 2.
      Adherence was seen in 54.95% on the basis of MMAS-9, whereas physician's
      assessment reported adherence in 90.39% of patients. Using the chi2 test, no
      relationship was found between the two assessment techniques. There was a
      significant relationship between major molecular response status and adherence by
      physician's assessment and MMAS-9 ( P < .001). Bivariate analysis by logistic fit
      showed a good relation between the MMAS-9 score and the BCR-ABL/ABL ratio (IS),
      chi2 (1,220) = 135.45 ( P < .001). On multivariate analysis, enrolment in the
      Novartis Oncology Access program (a patient assistance program) was significantly
      associated with adherence ( P = .012). CONCLUSION: This study highlights the lack
      of adherence in real-world settings and the various factors responsible. Such
      studies are important from a public health services perspective in various
      settings around the world because they may lead to corrective action being taken
      at the institutional level.

PMID- 30241225
TI  - Availability of WHO Essential Medicines for Cancer Treatment in Botswana.
AB  - PURPOSE: Stock outs of cancer drugs are potentially fatal but have not been
      systematically studied in low- and middle-income countries. The aim of this study
      was to determine the availability and alignment of the Botswana National
      Essential Medicines List (NEML) for cancer drugs with the WHO's Essential
      Medicines List (EML). METHODS: The availability and cost of cancer drugs were
      analyzed using data from a weekly stock catalog sent by Botswana's Central
      Medical Store to all pharmacy departments in government hospitals. Comparative
      data were extracted from the WHO EML and the "International Drug Price Indicator
      Guide-2014" from the Management Sciences for Health. Interviews with key
      informants were used to collect data on the Botswana NEML and the drug supply
      chain in the public sector. RESULTS: The 2015 Botswana NEML for cancer had 80.5%
      alignment with the WHO EML. At least 40% of essential drugs were out of stock for
      a median duration of 30 days in 2015. Stock outs affected chemotherapy drugs
      included in first-line regimens for treating potentially curable diseases such as
      cervical, breast, and colorectal cancer and were not associated with buyer price
      of therapy. Analyses showed that the median price ratio for procured drugs was
      greater than 1 for 61% of the NEML drugs, which suggests inefficiency in
      procurement in the public sector. CONCLUSIONS: Botswana has one of the highest
      alignments of NEML to the WHO EML in the sub-Saharan African region, which is
      consistent with investment in the health care system evident in other clinical
      spheres. Better quantification of chemotherapy requirements using data from the
      National Cancer Registry and resource-sensitive treatment guidelines can help
      reduce stock outs and facilitate more effective and efficient procurement
      processes.

PMID- 30241226
TI  - Promoting Clinical Breast Evaluations in a Lower Middle-Income Country Setting:
      An Approach Toward Achieving a Sustainable Breast Health Program.
AB  - PURPOSE: To promote a systems-based approach for the early detection and
      downstaging of breast cancer at presentation in the remote mountainous region of
      Gorno Badakhshan Autonomous Oblast (GBAO), Tajikistan, by introducing breast
      cancer awareness into the community and training health care professionals in
      clinical breast evaluation (CBE). METHODS: Through a public-private partnership
      between the Ministry of Health, the Aga Khan Health Services, Tajikistan, and the
      Aga Khan Health Board, we organized breast cancer screening in the community and
      trained family medicine doctors (FMDs) and family medicine nurses (FMNs) in CBE.
      We identified and trained CBE master trainers, who, in turn, systematically
      trained FMNs to conduct CBEs in each of the remote regional clinics. RESULTS:
      Between 2014 and 2017, 47 FMDs (85% of all FMDs in GBAO), 166 FMNs (55% of all
      FMNs in GBAO), and six master trainers were trained. Of 3,556 women who were
      screened, abnormal CBEs were noted in 696 of them (20%). Of the last 1,101 CBEs
      that were performed by trainee FMNs, with secondary CBEs by master trainers, the
      rate of abnormal CBEs plateaued at 9%. A total of 18 women were diagnosed with
      breast cancer-2.6% of abnormal CBEs and 0.5% of all screened women. CONCLUSION: A
      dual-pronged approach of community awareness and CBE training of health care
      professionals, supported by CBE master trainers, offers a sustainable approach
      for the early detection of breast pathology. We observed anecdotal evidence of
      clinical early-stage detection over time with improved CBE proficiency and
      community acceptance. Sustaining this program will require advocacy by health
      care providers and a responsive public policy to support the early detection and
      treatment of breast cancer across the region.

PMID- 30241227
TI  - Adjuvant Carboplatin and Paclitaxel Chemotherapy Followed by Radiotherapy in High
      Risk Endometrial Cancer: A Retrospective Analysis.
AB  - PURPOSE: The best adjuvant treatment in high-risk endometrial cancer remains
      unclear. Although adjuvant chemotherapy seems to improve overall survival (OS) in
      locally advanced disease, the role of adding radiotherapy is not certain. We
      evaluated the outcomes of patients with high-risk endometrial cancer treated with
      adjuvant chemotherapy followed by radiotherapy. PATIENTS AND METHODS: We
      performed a retrospective analysis of patients with high-risk endometrial cancer
      (endometrioid histology stages III to IVA or carcinosarcoma, clear cell, or
      serous histology stages I to IVA) treated with adjuvant carboplatin and
      paclitaxel, followed by radiotherapy, from 2010 to 2017 at a Brazilian cancer
      center. The Kaplan-Meier method was used for survival analysis, and prognostic
      factors were analyzed using the Cox proportional hazards model. RESULTS: One
      hundred forty-six consecutive patients were evaluated. The OS rates were 86.2% at
      3 years and 75.4% at 5 years. OS was significantly affected by pelvic
      lymphadenectomy ( P = .001) and positive peritoneal cytology ( P < .001). Three-
      and 5-year disease-free survival (DFS) rates were 78.3% and 69.5%, respectively.
      The initial site of recurrence was limited to the pelvis in 4.1% of patients,
      within the abdomen in 1.3%, and extra-abdominal in 11.6%. Patients with grade 1
      or 2 endometrioid carcinoma had better prognosis than patients with endometrioid
      carcinoma grade 3 or nonendometrioid histology (3-year DFS, 93.67% v 68.5%,
      respectively; P = .0017). CONCLUSION: Adjuvant carboplatin and paclitaxel,
      followed by radiotherapy, is effective in high-risk endometrial cancer and
      associated with low rates of pelvic recurrence, which might be explained by the
      addition of radiotherapy. The high-risk group is heterogeneous, and the benefit
      of adjuvant treatment in patients with grade 1 or 2 endometrioid carcinoma is
      less clear.

PMID- 30241228
TI  - Impact of Breast Cancer Early Detection Training on Rwandan Health Workers'
      Knowledge and Skills.
AB  - PURPOSE: In April 2015, we initiated a training program to facilitate earlier
      diagnosis of breast cancer among women with breast symptoms in rural Rwanda. The
      goal of this study was to assess the impact of the training intervention in
      breast cancer detection on knowledge and skills among health center nurses and
      community health workers (CHWs). METHODS: We assessed nurses' and CHWs' knowledge
      about breast cancer risk factors, signs and symptoms, and treatability through a
      written test administered immediately before, immediately after, and 3 months
      after trainings. We assessed nurses' skills in clinical breast examination
      immediately before and after trainings and then during ongoing mentorship by a
      nurse midwife. We also examined the appropriateness of referrals made to the
      hospital by health center nurses. RESULTS: Nurses' and CHWs' written test scores
      improved substantially after the trainings (overall percentage correct increased
      from 73.9% to 91.3% among nurses and from 75.0% to 93.8% among CHWs ( P < .001
      for both), and this improvement was sustained 3 months after the trainings. On
      checklists that assessed skills, nurses' median percentage of actions performed
      correctly was 24% before the training. Nurses' skills improved significantly
      after the training and were maintained during the mentorship period (the median
      score was 88% after training and during mentorship; P < .001). In total, 96.1% of
      patients seen for breast concerns at the project's hospital-based clinic were
      deemed to have been appropriately referred. CONCLUSION: Nurses and CHWs
      demonstrated substantially improved knowledge about breast cancer and skills in
      evaluating and managing breast concerns after brief trainings. With adequate
      training, mentorship, and established care delivery and referral systems, primary
      health care providers in sub-Saharan Africa can play a critical role in earlier
      detection of breast cancer.

PMID- 30241230
TI  - Model for Early Detection of Breast Cancer in Low-Resource Areas: The Experience
      in Peru.
AB  - PURPOSE: Late-stage breast cancer detection should be something of the past;
      however, it is still all too common in low-resource areas, including Peru, where
      57% of women diagnosed with cancer are diagnosed at stage III or IV disease.
      Early detection of breast cancer is feasible in low-resource semirural and rural
      areas where mammography is rarely accessible. METHODS: PATH collaborated with
      Peruvian health institutions at local, regional, and national levels to design
      and implement a model of care for the early detection of breast cancer in Peru.
      The model includes training health promoters for community outreach, professional
      midwives in clinical breast exam, doctors to perform fine-needle aspiration
      biopsy sampling with ultrasound to triage, and patient navigators to ensure
      patients follow through with treatment. RESULTS: In a northern region of Peru,
      400 individuals, including health promoters, midwives, doctors, and volunteers,
      received early-detection training in two phases. In Peru, local health
      professionals continue to refine and improve methods and materials using locally
      available resources, and the Peruvian health information system now includes
      specific breast cancer detection categories. Despite challenges and limited
      resources, the model is effective, and partnership with government health
      administrations improves health systems and benefits the population. CONCLUSION:
      Given the absence of screening mammography, the public health challenge is to
      bring breast cancer early detection and diagnostic services closer to women's
      homes and to ensure appropriate follow-up and care. The model is eminently
      transferable with appropriate adaptation and should now be tested in other
      settings within and outside of Peru.

PMID- 30241229
TI  - The African Esophageal Cancer Consortium: A Call to Action.
AB  - Esophageal cancer is the eighth most common cancer worldwide and the sixth most
      common cause of cancer-related death; however, worldwide incidence and mortality
      rates do not reflect the geographic variations in the occurrence of this disease.
      In recent years, increased attention has been focused on the high incidence of
      esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of
      Africa, extending from Ethiopia to South Africa. Nascent investigations are
      underway at a number of sites throughout the region in an effort to improve our
      understanding of the etiology behind the high incidence of ESCC in this region.
      In 2017, these sites established the African Esophageal Cancer Consortium. Here,
      we summarize the priorities of this newly established consortium: to implement
      coordinated multisite investigations into etiology and identify targets for
      primary prevention; to address the impact of the clinical burden of ESCC via
      capacity building and shared resources in treatment and palliative care; and to
      heighten awareness of ESCC among physicians, at-risk populations, policy makers,
      and funding agencies.

PMID- 30241231
TI  - Current and Future Burden of Prostate Cancer in Songkhla, Thailand: Analysis of
      Incidence and Mortality Trends From 1990 to 2030.
AB  - PURPOSE: Prostate cancer is the second most common malignancy among men
      worldwide, and it poses a significant public health burden that has traditionally
      been limited mostly to developed countries. However, the burden of the disease is
      expected to increase, affecting developing countries, including Thailand. We
      undertook an analysis to investigate current and future trends of prostate cancer
      in the province of Songkhla, Thailand, using data from the Songkhla Cancer
      Registry from 1990 to 2013. METHODS: Joinpoint regression analysis was used to
      examine trends in age-adjusted incidence and mortality rates of prostate cancer
      and provide estimated annual percent change (EAPC) with 95% CIs. Age-period
      cohort (APC) models were used to assess the effect of age, calendar year, and
      birth cohort on incidence and mortality rates. Three different methods
      (Joinpoint, Nordpred, and APC) were used to project trends from 2013 to 2030.
      RESULTS: Eight hundred fifty-five cases of prostate cancer were diagnosed from
      1990 to 2013 in Songkhla, Thailand. The incidence rates of prostate cancer
      significantly increased since 1990 at an EAPC of 4.8% (95% CI, 3.6% to 5.9%).
      Similarly, mortality rates increased at an EAPC of 5.3% (95% CI, 3.4% to 7.2%).
      The APC models suggest that birth cohort is the most important factor driving the
      increased incidence and mortality rates of prostate cancer. Future incidence and
      mortality of prostate cancer are projected to continue to increase, doubling the
      rates observed in 2013 by 2030. CONCLUSION: It is critical to allocate resources
      to provide care for the men who will be affected by this increase in prostate
      cancer incidence in Songkhla, Thailand, and to design context-appropriate
      interventions to prevent its increasing burden.

PMID- 30241232
TI  - Distress Management in Patients With Head and Neck Cancer Before Start of
      Palliative Chemotherapy: A Practical Approach.
AB  - PURPOSE: This study reports the incidence of distress, the factors associated
      with distress, and a practical strategy to resolve distress in patients with head
      and neck cancer who are starting palliative chemotherapy. METHODS: Adult patients
      with head and neck cancer planned for palliative chemotherapy underwent distress
      screening before the start of treatment as part of this single-arm prospective
      study. Patients who had a distress score > 3 on the National Comprehensive Cancer
      Network (NCCN) distress thermometer were counseled initially by the clinician.
      Those who continued to have high distress after the clinician-led counseling were
      referred to a clinical psychologist and were started on palliative chemotherapy.
      After counseling, distress was measured again. The relation between baseline
      distress and compliance was tested using Fisher's exact test. RESULTS: Two
      hundred patients were enrolled, and the number of patients with high distress was
      89 (44.5% [95% CI, 37.8% to 51.4%]). The number of patients who had a decrease in
      distress after clinician-led counseling (n = 88) was 52 (59.1% [95% CI, 48.6% to
      68.8%]) and after psychologist-led counseling (n = 32) was 24 (75.0% [95% CI,
      57.6% to 72.2%]; P = .136). Compliance rates did not differ between the patients
      with or without a high level of distress at baseline (74.2% v 77.4%, P = .620).
      CONCLUSION: The incidence of baseline distress is high in patients awaiting the
      start of palliative chemotherapy. It can be resolved in a substantial number of
      patients using the strategy of clinician-led counseling, with additional referral
      to a clinical psychologist as required. Patients with a greater number of
      emotional problems usually require psychologist-led counseling.

PMID- 30241233
TI  - Bisphosphonate Combination Therapy in the Management of Postchemotherapy
      Avascular Necrosis of the Femoral Head in Adolescents and Young Adults: A
      Retrospective Study From India.
AB  - PURPOSE: With improved survival after chemotherapy for acute lymphoblastic
      leukemia (ALL), it is imperative to maintain good quality of life as part of the
      management of post-therapy adverse effects. Avascular necrosis of the femoral
      head (AVNFH) is one such adverse effect. A need exists for a therapy that
      ameliorates discomfort, provides a productive life, is cost effective, and is
      joint preservative. We conducted the current study to evaluate the response to
      bisphosphonate in the nonsurgical management of AVNFH in adolescents and young
      adults (AYA) who receive treatment for ALL. MATERIALS AND METHODS: This is a
      retrospective study of 20 AYA patients-34 affected hips-who received zolendronic
      acid 5 mg intravenously each year along with oral alendronate 70 mg weekly for 3
      years. Clinical evaluation was performed by using the Visual Analog Scale and the
      Harris Hip Score. Radiographs were used to classify the Ficat-Arlet stage,
      monitor radiologic collapse, and evaluate the rate of progression. RESULTS: Pain
      relief with a drop in the Visual Analog Scale score was observed at a mean
      duration of 5.2 weeks (range, 3 weeks to 11 weeks) after the start of therapy.
      Radiologic progression by one grade was observed in 12 hips (35.3%), and only one
      hip (2.94%) showed progression by two grades. At a mean follow-up of 50.3 months,
      31 affected hips (91.1%) had a satisfactory clinical outcome and had not required
      any surgical intervention. The proportion of hips that required total hip
      arthroplasty were 0%, 5%, and 22.2% in Ficat-Arlet stage I, II, and III,
      respectively. CONCLUSION: The combination of intravenous zolendronic acid and
      oral alendronate provides a pragmatic solution for the management of AVNFH after
      therapy for ALL in AYA patients. This therapy is safe, effective, and well
      tolerated.

PMID- 30241235
TI  - Importance of Nongovernmental Organizations for the Establishment of a Successful
      Hematopoietic Stem-Cell Transplantation Program in a Developing Country.
AB  - PURPOSE: In low- and middle-income countries with limited resources, the success
      of a hematopoietic stem-cell transplantation (HSCT) program relies directly on
      its affordability while obtaining similar outcomes to developed regions. The
      objective of this study was to describe the experience of a tertiary/referral
      center in Mexico City performing HSCT with the subsidy of a nongovernmental
      organization (NGO). PATIENTS AND METHODS: We performed a retrospective analysis
      including 146 patients who underwent HSCT at the National Institutes of Health
      Sciences and Nutrition Salvador Zubiran and were subsidized by the NGO Unidos.
      RESULTS: Seventy-five patients (51%) and 71 patients (49%) underwent autologous
      and allogeneic HSCT, respectively. The median age was 30 years, 56% did not
      obtain a bachelor's degree, 79% had a low socioeconomic level, and 75% were
      unemployed. None had any health coverage. According to the real patient out-of
      pocket expense, the subsidy by Unidos corresponded to 88% and 72% in autologous
      and allogeneic HSCT, respectively. CONCLUSION: Our results highlight that
      undergoing an HSCT was feasible for vulnerable patients because of the subsidy of
      medications and chemotherapy by Unidos. Therefore, creating NGOs in developing
      countries is important to provide complex medical procedures, such as HSCT, at
      limited-resource centers to underserved populations while obtaining good
      outcomes.

PMID- 30241234
TI  - Retinoblastoma in Sub-Saharan Africa: Case Studies of the Republic of Cote
      d'Ivoire and the Democratic Republic of the Congo.
AB  - PURPOSE: In most low-income countries, the diagnosis of retinoblastoma is
      delayed, resulting in a severe prognosis. The objectives of this study were to
      describe the access to diagnosis and care of children diagnosed with
      retinoblastoma and the challenges in two sub-Saharan African countries: the
      Republic of Cote d'Ivoire and the Democratic Republic of the Congo. PATIENTS AND
      METHODS: A descriptive cross-sectional study was conducted. Data were collected
      from the medical records of patients admitted during the period of January 1,
      2013 to December 31, 2014. Data were entered and analyzed using Epi Info7.1
      software and SAS 9.3. RESULTS: One hundred sixteen cases of retinoblastoma were
      collected, including 60 boys and 56 girls. The median diagnosis age was 3 years
      for both countries. Ninety-eight patients (84%) had unilateral retinoblastoma.
      Most of the patients presented with advanced disease (76% had extraocular
      retinoblastoma). Median time between initial symptoms and diagnosis was 8.5
      months (range, 0.4 to 116.7 months). Median time between diagnosis and treatment
      initiation was 31 days (range, 0 to 751 days). The median cost for the treatment
      of the disease was estimated at $1,954 per patient. CONCLUSION: Late diagnosis of
      retinoblastoma, with extraocular disease, occurs frequently in both African
      countries. It is associated with delay in initiating treatment, and the cost of
      the treatment remains unaffordable for most of the families. Support groups for
      parents of affected children and the support of the Franco-African Pediatric
      Oncology Group remain important in improving early diagnosis and providing
      treatment in sub-Saharan African countries.

PMID- 30241236
TI  - Understanding Men's Perceptions of Human Papillomavirus and Cervical Cancer
      Screening in Kampala, Uganda.
AB  - PURPOSE: This preliminary study explores Ugandan men's knowledge and attitudes
      about human papillomavirus (HPV), cervical cancer, and screening. METHODS: A
      local physician led an education session about cervical cancer for 62 men in
      Kisenyi, Kampala in Uganda. Trained nurse midwives administered surveys to assess
      knowledge and attitudes before and after the education session. RESULTS: From the
      pre-education survey, only 24.6% of men had heard of HPV previously, and 59% of
      men had heard of cervical cancer. Posteducation, 54.5% of men believed only women
      could be infected with HPV and 32.7% of men believed antibiotics could cure HPV.
      Despite their limited knowledge, 98.2% of men stated they would support their
      partners to receive screening for cervical cancer, and 100% of men surveyed
      stated they would encourage their daughter to get the HPV vaccine if available.
      CONCLUSIONS: Knowledge of HPV and cervical cancer among Ugandan men is low. Even
      after targeted education, confusion remained about disease transmission and
      treatment. Ongoing education programs geared toward men and interventions to
      encourage spousal communication about reproductive health and shared decision
      making may improve awareness of cervical cancer prevention strategies.

PMID- 30241238
TI  - What Global Oncology Needs: Mutual Learning and More Funding.

PMID- 30241237
TI  - Building Oncofertility Core Competency in Developing Countries: Experience From
      Egypt, Tunisia, Brazil, Peru, and Panama.
AB  - PURPOSE: Little is known about oncofertility practice in developing countries
      that usually suffer from a shortage of health services, especially those related
      to cancer care. MATERIALS AND METHODS: To learn more about oncofertility practice
      in developing countries, we generated a survey to explore the barriers and
      opportunities associated with oncofertility practice in five developing countries
      from Africa and Latin America within our Oncofertility Consortium Global Partners
      Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected,
      reviewed, and discussed. RESULTS: Common barriers were identified by each
      country, including financial barriers (lack of insurance coverage and high out-of
      pocket costs for patients), lack of awareness among providers and patients,
      cultural and religious constraints, and lack of funding to help to support
      oncofertility programs. CONCLUSION: Despite barriers to care, many opportunities
      exist to grow the field of oncofertility in these five developing countries. It
      is important to continue to engage stakeholders in developing countries and use
      powerful networks in the United States and other developed countries to aid in
      the acceptance of oncofertility on a global level.

PMID- 30241239
TI  - Findings of Multiple Myeloma in Afro-Caribbean Patients in the United States.
AB  - BACKGROUND: Multiple myeloma (MM) is the second most common malignancy in the
      United States and has a higher incidence in the black and Afro-Caribbean
      population. There remain limited data on disease presentation and clinical
      characteristics in this patient group in the United States. The clinical profile
      of MM in this underrepresented patient group is described here. METHODS: This
      retrospective study was conducted at Kings County Hospital, an urban New York
      City hospital in a majority Afro-Caribbean neighborhood. Data from patients
      diagnosed with MM from 2000 through 2013 were collected from the institution's
      tumor registry. Clinical and demographic characteristics of these patients were
      then analyzed. RESULTS: Patients with a diagnosis of MM were identified (N =
      287). Data were available for 231 patients and of these, 97% self-identified as
      black. 55% were female, and there was a male-to-female ratio of 1:1.2. The mean
      age of female patients was 64 years; that of male patients was 63 years. Of the
      231 patients, 81% had anemia, 68% had bone lesions, 47% had renal impairment, and
      29% had hypercalcemia. Low levels of monoclonal protein were present in 27% of
      patients and 57% had disease of International Staging System stages I and II.
      Women had higher BMI than men. CONCLUSION: The mean age of presentation of MM in
      Afro-Caribbean patients is similar to that in the standard population; however,
      unlike the general US population, there was a higher incidence in women; mean BMI
      of women also was higher than that of male patients. A sizeable percentage of
      Afro-Caribbean patients with MM presented with low levels of monoclonal protein
      in the presence of multiorgan involvement and damage, suggesting the need for
      early and aggressive diagnostic testing.

PMID- 30241241
TI  - Global Survey of Clinical Oncology Workforce.
AB  - A lack of well-trained clinical oncologists can result in significant cancer
      health disparities. The magnitude of this problem around the world is poorly
      described in the literature. A comprehensive global survey of the clinical
      oncology workforce was conducted. Data on the number of clinical oncologists in
      93 countries were obtained from 30 references. The mortality-to-incidence ratio
      was estimated by using data on incidence and mortality rates from the GLOBOCAN
      2012 database; the ratio was > 70% in 26 countries (28%), which included 21
      countries in Africa (66%) and five countries in Asia (26%). Eight countries had
      no clinical oncologist available to provide care for patients with cancer. In 22
      countries (24%), a clinical oncologist would provide care for < 150 patients with
      a new diagnosis of cancer. In 39 countries (42%), a clinical oncologist would
      provide care for > 500 patients with cancer. In 27 countries (29%), a clinical
      oncologist would provide care for > 1,000 incident cancers, of which 25 were in
      Africa, two were in Asia, and none were in Europe or the Americas. The economic
      and social development status of a country correlates closely with the burden of
      cancer and the shortage of human resources. Addressing the shortage of clinical
      oncologists in regions with a critical need will help these countries meet the
      sustainable development goals for noncommunicable diseases by 2030.

PMID- 30241240
TI  - Outcomes in Treatment-Naive Patients With Metastatic Extremity Osteosarcoma
      Treated With OGS-12, a Novel Non-High-Dose Methotrexate-Based, Dose-Dense
      Combination Chemotherapy, in a Tertiary Care Cancer Center.
AB  - PURPOSE: Metastatic osteosarcoma is largely treated with high-dose methotrexate
      (HDMTX)-based therapy, especially in the pediatric population. This mandates
      complex pharmacokinetic monitoring in a costly inpatient setting to mitigate
      unpredictable serious toxicities. Hence, a non-HDMTX-based regimen is worth
      exploring, especially in India and low- and middle-income countries. MATERIALS
      AND METHODS: All consecutive treatment-naive patients with metastatic
      osteosarcoma were prospectively treated on the novel OGS-12 protocol consisting
      of sequential doublets of doxorubicin, cisplatin, and ifosfamide. Four cycles
      were administered as neoadjuvant therapy followed by planned curative intent
      surgery and metastasectomy when feasible, followed by four cycles of adjuvant
      chemotherapy. Baseline characteristics, histologic response, event-free survival
      (EFS), overall survival (OS), and toxicity data were prospectively collected.
      RESULTS: Three hundred seventeen patients were enrolled onto the OGS-12 protocol
      from 2011 to 2014, of whom 80 (25%) had metastatic disease; median age was 17
      years. The majority of patients were nutritionally challenged with high-risk
      features. At presentation, 83% of patients (66 patients) had lung metastases.
      After neoadjuvant chemotherapy, 57% of patients were histologically good
      responders. Four-year EFS and OS rates were 24% and 27%, respectively, in the
      intent-to-treat population and 27% and 29%, respectively, in the per-protocol
      analysis. Significant grade 3 or 4 toxicities were febrile neutropenia (51%),
      thrombocytopenia (36%), and anemia (54%). Histologic response was an independent
      predictor for EFS and OS in patients who underwent surgery. Surgical intervention
      was found to be significant for survival in univariable analysis. CONCLUSION: The
      novel, low-cost, non-HDMTX-based, dose-dense OGS-12 regimen has shown comparable
      outcomes to international standards in metastatic osteosarcomas and is worthy of
      wider clinical application. An aggressive multimodality approach may result in
      long-term survival in a select group of patients and, hence, is worth
      considering.

PMID- 30241242
TI  - Epidemiological, Clinical, and Histopathological Features of Breast Cancer in
      Haiti.
AB  - PURPOSE: Little is known about the epidemiology of breast cancer in developing
      countries, and Haiti has perhaps the least data of any country in the Western
      Hemisphere. METHODS: We conducted a retrospective review of all patients enrolled
      in an ongoing breast cancer treatment program in Port-au-Prince, Haiti, from July
      1, 2013, through June 30, 2017. Data were drawn from each patient's electronic
      medical record, paper chart, and biopsy results. RESULTS: The records of 525
      women with breast cancer were reviewed for this study. The median age at
      presentation was 49 years (n = 507). The risk factors observed were as follows:
      postmenopausal, 50.8% (n = 354); nulliparity, 15.7% (n = 338); hormonal
      contraception use, 35.0% (n = 309); never breastfed, 20.6% (n = 316); family
      history of any cancer, 22.0% (n = 295); overweight, 51.5% (n = 332); and smoking,
      5.0% (n = 338). Of all those staged, 83.9% (n = 447) of the patients presented
      with stage III/IV disease and more than half delayed care for > 12 months after
      first noticing a breast mass. For the subset of tumors for which estrogen
      receptor (ER; n = 245) and human epidermal growth factor receptor 2 (HER2; n =
      179) status was available, the prevalence of ER-positive tumors was 51.8%, of
      HER2-positive tumors was 19.6%, and of triple-negative tumors was 38.5%. The 12
      month mortality rate (n = 425) was 18.4% overall and 27.5% for those who
      presented with stage IV disease. Median survival was not reached. CONCLUSION:
      Breast cancer in Haiti presents at an early age and advanced stage. Triple
      negative, ER-negative, and high-grade tumors are common. Delays in seeking care
      and incomplete treatment likely contribute to the high mortality rate; however,
      as in black women in the United States, the distribution of tumor types may
      contribute to disparate outcomes.

PMID- 30241243
TI  - Desire for Information and Preference for Participation in Treatment Decisions in
      Patients With Cancer Presenting to the Department of General Surgery in a
      Tertiary Care Hospital in India.
AB  - PURPOSE: Providing appropriate information to patients about their illness helps
      them to cope with the diagnosis. Shared decision making is a key concept in
      managing patients with cancer. There are no data available about the desire for
      information and preference for participation in treatment decisions among Indian
      patients with cancer. The objective of this study was to estimate the proportion
      of patients who have information needs and to study the patient preference for
      participation in treatment decisions and the factors associated with them.
      METHODS: A cross-sectional survey was conducted among patients with cancer older
      than 18 years. They were interviewed with a questionnaire after signing an
      informed consent. The association of sex, educational level, residence, diagnosis
      (type of cancer), Eastern Cooperative Oncology Group performance status, and
      treatment status with information needs and decision-making preference was
      analyzed using chi2 test. RESULTS: Approximately 81% of patients said that they
      had an absolute need to know if the illness was cancer, and > 70% of patients
      either had an absolute need to know or would like to know about the prognosis,
      treatment options, and adverse effects. Regarding the decision-making
      preferences, 97% wanted their treating physicians to make the decision regarding
      their treatment, and 66% preferred to share decision making with their family.
      CONCLUSION: The majority of the patients with cancer expressed a need for knowing
      whether they had cancer. When it comes to treatment decisions, most of them
      preferred a passive role, and the majority wanted to involve their families in
      the decision-making process. We recommend that the treating physician should
      elicit the patient's preference in participating in treatment decisions and their
      preference about involving their family in making treatment decisions.

PMID- 30241244
TI  - Methodology to Forecast Volume and Cost of Cancer Drugs in Low- and Middle-Income
      Countries.
AB  - PURPOSE: In low- and middle-income countries (LMICs), frequent outages of the
      stock of cancer drugs undermine cancer care delivery and are potentially fatal
      for patients with cancer. The aim of this study is to describe a methodologic
      approach to forecast chemotherapy volume and estimate cost that can be readily
      updated and applied in most LMICs. METHODS: Prerequisite data for forecasting are
      population-based incidence data and cost estimates per unit of drug to be
      ordered. We used the supplementary guidelines from the WHO list of essential
      medicines for cancer to predict treatment plans and ordering patterns. We used de
      identified aggregate data from the Botswana National Cancer Registry to estimate
      incident cases. The WHO Management Sciences for Health International Price
      Indicator was used to estimate unit costs per drug. RESULTS: Chemotherapy volume
      required for incident cancer cases was estimated as the product of the
      standardized dose required to complete a full treatment regimen per patient, with
      a given cancer diagnosis and stage, multiplied by the total number of incident
      cancer cases with the respective diagnosis. The estimated chemotherapy costs to
      treat the 10 most common cancers in the public health care sector of Botswana is
      approximately 2.3 million US dollars. An estimated 66% of the budget is allocated
      to costs of rituximab and trastuzumab alone, which are used by approximately 10%
      of the cancer population. CONCLUSION: This method provides a reproducible
      approach to forecast chemotherapy volume and cost in LMICs. The chemotherapy
      volume and cost outputs of this methodology provide key stakeholders with
      valuable information that can guide budget estimation, resource allocation, and
      drug-price negotiations for cancer treatment. Ultimately, this will minimize drug
      shortages or outages and reduce potential loss of lives that result from an
      erratic drug supply.

PMID- 30241246
TI  - Impact of Cancer Awareness Drive on Generating Awareness of and Improving
      Screening for Cervical Cancer: A Study Among Schoolteachers in India.
AB  - PURPOSE: Cervical cancer is the second most common cancer in India. Our study
      assessed the level and impact of awareness programs in the adoption of safe
      practices in prevention and early detection. METHODS: This assessment was part of
      a Pink Chain Campaign, the mission of which is to fight cancer. During cancer
      awareness events from 2013 to 2015 at various women's colleges in different parts
      in India, a pretest related to cervical cancer was followed by an awareness
      program. A post-test was conducted 6 months and 1 year later. RESULTS: A total of
      872 of 985 teachers participated in the study, for a response rate of 88.5%. Mean
      age of the population was 42.4 years. There was a significant increase in the
      level of knowledge regarding cervical cancer at 6 months, which was sustained at
      1 year. Regarding cervical cancer screening, knowledge and practice of the
      Papanicolaou (Pap) test as a screening test for cervical cancer among teachers
      were changed significantly at 6 months and 1 year. More than 75% of teachers were
      educated by physicians about the Pap test. At the time of the post-test, there
      was a significant change in alcohol and smoking habits. The main reasons for not
      undergoing a screening test were ignorance (50%), lethargic attitude (44.8%), and
      lack of time (34.6%). CONCLUSION: The level of knowledge of cervical cancer was
      poor. A significant increase in the level of knowledge of cervical cancer among
      the population was found after this study. To inculcate safe lifestyle practices,
      awareness programs should be conducted more widely and frequently.

PMID- 30241245
TI  - Perspectives on Strengthening Cancer Research and Control in Latin America
      Through Partnerships and Diplomacy: Experience of the National Cancer Institute's
      Center for Global Health.
AB  - According to the Pan American Health Organization, noncommunicable diseases,
      including cancer, are the leading causes of preventable and premature death in
      the Americas. Governments and health care systems in Latin America face numerous
      challenges as a result of increasing morbidity and mortality from cancer.
      Multiple international organizations have recognized the need for collaborative
      action on and technical support for cancer research and control in Latin America.
      The Center for Global Health at the US National Cancer Institute (NCI-CGH) is one
      entity among many that are working in the region and has sought to develop a
      strategy for working in Latin America that draws on and expands the collaborative
      potential of engaged, skilled, and diverse partners. NCI-CGH has worked toward
      developing and implementing initiatives in collaboration with global partners
      that share the common objectives of building a global cancer research community
      and translating research results into evidence-informed policy and practice. Both
      objectives are complementary and synergistic and are additionally supported by an
      overarching strategic framework that is focused on partnerships and science
      diplomacy. This work highlights the overall strategy for NCI-CGH engagement in
      Latin America through partnerships and diplomacy, and highlights selected
      collaborative efforts that are aimed at improving cancer outcomes in the region.

PMID- 30241247
TI  - Cancer Supportive and Survivorship Care in Singapore: Current Challenges and
      Future Outlook.
AB  - Despite being a relatively young nation, Singapore has established itself as a
      leading multifaceted medical hub, both regionally and globally. Although
      Singapore continues to pursue excellence in oncology care, cancer supportive care
      and survivorship care remain in the infancy stage. In an effort to advance this
      important aspect of oncology care in Singapore, the first cancer supportive and
      survivorship care forum was held in December 2016, involving 74 oncology
      practitioners. The primary goals of this forum were to raise awareness of the
      importance of cancer supportive and survivorship care and to provide a platform
      for oncology practitioners of diverse backgrounds to converge and address the
      challenges associated with the delivery of cancer supportive and survivorship
      care in Singapore. Key challenges identified during this forum included, but were
      not limited to, care fragmentation in an oncologist-centric model of care, poor
      integration of allied health and rehabilitation services, passive engagement of
      community partners, lack of specialized skill sets and knowledge in supportive
      and survivorship care, and patient-related barriers such as poor health literacy.
      The survivorship care model commonly used in Singapore places an imbalanced
      emphasis on surveillance for cancer recurrence and second primary cancers, with
      little attention given to the supportive and survivorship needs of the survivors.
      In summary, these challenges set the stage for the development and use of a more
      survivor-centric model, one that focuses not only on cancer surveillance, but
      also on the broad and unique physical and psychosocial needs of survivors of
      cancer in Singapore.

PMID- 30241248
TI  - Autotransplantations Without Cryopreservation.

PMID- 30241249
TI  - Comparison of the Accuracy of Papanicolaou Test Cytology, Visual Inspection With
      Acetic Acid, and Visual Inspection With Lugol Iodine in Screening for Cervical
      Neoplasia in Southeast Nigeria.
AB  - PURPOSE: This study aimed to compare the accuracy of Papanicolaou test cytology,
      visual inspection with 5% acetic acid (VIA), and visual inspection with Lugol
      iodine (VILI) in the detection of premalignant and malignant lesions of the
      cervix. MATERIALS AND METHODS: This was a cross-sectional comparative study of
      200 consenting participants at the Federal Teaching Hospital, Abakaliki over a 6
      month period. All the participants had Papanicolaou test cytology. Subsequently,
      they were classified into two groups of 100 each through systematic random
      sampling: group 1 had VIA and group 2 had VILI. Thereafter, all the participants
      had cervical punch biopsy at the 6 and 12 o'clock cervical positions. Cervical
      punch biopsy was also done on the suspicious lesions of the cervix irrespective
      of their positions. The tests of validity of the three methods were calculated
      using the histology of the biopsy specimen as the gold standard. P value <= .05
      was considered to be statistically significant. RESULTS: Among the VIA group, 19
      (19%) had cervical epithelial abnormalities on Papanicolaou test cytology, and
      VIA was positive in 14 (14%). Histology results showed cervical neoplasia in 15
      (15%) of the participants. Among the VILI group, 15 (15%) had cervical epithelial
      abnormalities on Papanicolaou test cytology, and VILI was positive in 19 (19%).
      Histology results showed cervical neoplasia in 15 (15%) of the participants.
      There was no significant difference in overall accuracy of Papanicolaou test
      cytology, VIA, and VILI. The overall accuracy of the Papanicolaou test cytology
      plus VIA was significantly more than Papanicolaou test cytology alone.
      CONCLUSION: VIA or VILI can be used as a stand-alone cervical cancer screening
      test when compared with Papanicolaou test cytology, particularly in resource
      limited settings. VIA can also complement Papanicolaou test cytology.

PMID- 30241250
TI  - Levels and Trends of Esophageal and Stomach Cancer Mortality in Sub-Saharan
      Africa and the Caribbean.

PMID- 30241251
TI  - Illness Understanding and End-of-Life Care Communication and Preferences for
      Patients With Advanced Cancer in South Africa.
AB  - PURPOSE: The understanding of patients with cancer of their condition and their
      wishes regarding care as they approach end of life (EoL) have been studied more
      in high-income countries than in low- and middle-income countries (LMICs).
      PATIENTS AND METHODS: Data were analyzed from a cohort study (N = 221) of
      patients with advanced cancer who were recruited from a palliative care center in
      Soweto, South Africa (LMIC), between May 2016 and June 2017. Patients were asked
      about their understanding of their illness, estimated life expectancy, EoL care
      communication, and EoL care preferences. RESULTS: Only 13 patients (5.9%)
      acknowledged that they were terminally ill; nine patients (4.1%) estimated
      accurately that they had months, not years, left to live. A total of 216 patients
      (97.7%) reported that they had not had an EoL care discussion with their
      physician, and 170 patients (76.9%) did not want to know their prognosis even if
      the doctor knew it. Most patients preferred comfort care (72.9%; n = 161) to life
      extending care (14.0%; n = 31), and did not want to be kept alive using extreme
      measures (80.5%; n = 178) or have their doctors do everything possible to extend
      their lives (78.3%; n = 173). Finally, 127 patients (57.5%) preferred to die at
      home, and 51 (23.1%) preferred to die in the hospital. Most patients (81.0%; n =
      179) had funeral plans. CONCLUSION: South African patients demonstrated less
      awareness of the fact that they were terminally ill, were less likely to have
      discussed their prognosis with their doctor, and more strongly preferred comfort
      care to life-extending EoL care than US and other LMIC patients in prior
      research. These differences highlight the need for culturally appropriate,
      patient-centered EoL care for South African patients with advanced cancer as well
      as to determine individual preferences and needs in all EoL settings.

PMID- 30241254
TI  - Palliative Care Program Development in a Low- to Middle-Income Country: Delivery
      of Care by a Nongovernmental Organization in India.
AB  - PURPOSE: Limited data describe the delivery of palliative care services in low-
      and middle-income countries. We describe delivery of care by the Trivandrum
      Institute of Palliative Sciences (TIPS) in Trivandrum, India. METHODS:
      Administrative records were used to describe case volumes, setting of care, and
      organizational expenditures. An estimate of cost per clinical encounter was
      derived by dividing 2016 monthly clinical expenditures by the number of patient
      visits. Costs are reported in US dollars and are corrected for Organization for
      Economic Co-operation and Development purchasing power parity (PPP). RESULTS: A
      total of 11,620 new patients were seen at TIPS during 2007 to 2016; 59% had
      cancer. The average annual growth rate in case volumes was 18% (480 new patients
      in 2007 and 1,882 in 2016). The proportion of patients with cancer increased over
      time from 56% in 2014 to 66% in 2016 ( P < .001). During 2014 to 2016, outpatient
      visits increased 26% (from 8,524 to 10,732), inpatient days increased 49% (from
      1,763 to 2,625), inpatient visits at other hospitals increased 41% (from 248 to
      417), and home visits increased 57% (from 3,951 to 6,186). Total clinical
      expenditures in 2016 were $288,489 (PPP corrected, $5.1 million). Between 2014
      and 2016, the cost of delivering care increased by 74%. The mean cost per
      clinical encounter in 2016 was $15 (PPP corrected, $263). CONCLUSION: Demand for
      palliative care services has increased substantially, with an increasing
      proportion related to cancer. The organization of clinical services by TIPS may
      serve as a model for the development of other palliative care programs in low-
      and middle-income countries.

PMID- 30241252
TI  - Challenges in Lung Cancer Screening in Latin America.
AB  - Lung cancer is the deadliest cancer worldwide and is of particular concern for
      Latin America. Its rising incidence in this area of the world poses myriad
      challenges for the region's economies, which are already struggling with limited
      resources to meet the health care needs of low- and middle-income populations. In
      this environment, we are concerned that regional governments are relatively
      unaware of the pressing need to implement effective strategies for the near
      future. Low-dose chest computed tomography (LDCT) for screening, and routine use
      of minimally invasive techniques for diagnosis and staging remain uncommon.
      According to results of the National Lung Screening Trial, LDCT lung cancer
      screening provided a 20% relative reduction in mortality rates among at-risk
      individuals. Nevertheless, this issue is still a matter of debate, particularly
      in developing countries, and it is not fully embraced in developing countries.
      The aim of this article is to provide an overview of what the standard of care is
      for lung cancer computed tomography screening around the world and to aid
      understanding of the challenges and potential solutions that can help with the
      implementation of LDCT in Latin America.

PMID- 30241253
TI  - Implementing a Childhood Cancer Outcomes Surveillance System Within a Population
      Based Cancer Registry.
AB  - PURPOSE: Approximately 80% of cases of childhood cancer occur in low- and middle
      income countries and are associated with high mortality rates. Assessing outcomes
      is essential for designing effective strategies to improve outcomes equally
      worldwide. We implemented a real-time surveillance system, VIGICANCER, embedded
      in a population-based cancer registry (PBCR) to assess childhood cancer outcomes.
      METHODS: VIGICANCER was established in 2009 as an integral part of Cali's PBCR to
      collect real-time data on outcomes of patients (age < 19 years) with a new
      diagnosis of cancer treated in pediatric oncology units in Cali, Colombia.
      Baseline and follow-up data (death, relapse, treatment abandonment, second
      neoplasms) were collected from medical records, hospital discharge logs,
      pathology reports, death certificates, and the National Public Health Insurance
      database. A quality assurance process was implemented for the system. RESULTS:
      From 2009 to 2013, data from 1,242 patients were included in VIGICANCER: 32% of
      patients were younger than 5 years, 55% were male, and 15% were Afro-descendants.
      International Classification of Childhood Cancer group I diagnoses predominated
      in all age groups except children younger than 1 year old, in whom CNS tumors
      predominated. Five-year overall survival for all cancers was 51.7% (95% CI, 47.9%
      to 55.4%) for children (< 15 years), and 39.4% (95% CI, 29.8% to 50.5%) for
      adolescents (15 to 18.9 years). Five-year overall survival for acute
      lymphoblastic leukemia was 55.6% (95% CI, 48.5% to 62.2%). CONCLUSION: Our study
      demonstrates the feasibility of implementing a real-time childhood cancer
      outcomes surveillance system embedded in a PBCR that can guide interventions to
      improve clinical outcomes in low- and middle-income countries.

PMID- 30241255
TI  - Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in
      Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With
      Different Resources.
AB  - PURPOSE: High-dose chemotherapy with autologous stem-cell rescue (SCR) is a key
      component of high-risk neuroblastoma (HRNB) therapy. Carboplatin, etoposide, and
      melphalan (CEM) or busulfan and melphalan (Bu/Mel) are the most evaluated,
      effective high-dose chemotherapy for HRNB on the basis of results from major
      cooperative group studies. Toxicity profiles vary between these regimens, and
      practice variation exists regarding the preferred high-dose therapy (HDT). We
      sought to evaluate the safety of HDT and autologous SCR for HRNB in a resource
      limited country (Egypt) compared with the resource-rich United States. PATIENTS
      AND METHODS: We performed a retrospective comparative review of single CEM-based
      HDT/SCR outcomes through day 100 for HRNB at the Fred Hutchinson Cancer Research
      Center (FH) in the United States (2005 to 2015) versus Bu/Mel-based HDT at El
      Sheikh Zayed Specialized Hospital (SZ) in Egypt (2009 to 2015). RESULTS: Forty
      four patients at FH and 77 patients at SZ were reviewed. Pretransplant hepatic
      comorbidities were significantly higher at SZ (29 of 77 v nine of 44; P = .05),
      with 19 of 77 patients at SZ having hepatitis infection. Engraftment was delayed
      after SZ-Bu/Mel therapy compared with FH-CEM therapy for neutrophils (median 12
      days v 10 days, respectively; P < .001) and platelets (median 20 days v 18 days,
      respectively; P < .001). Sinusoidal obstruction syndrome occurred later, after SZ
      Bu/Mel therapy (median 19 days v 7 days; P = .033), and four of eight cases were
      fatal (six of eight patients had underlying hepatitis infection), whereas three
      of three cases after FH-CEM therapy were moderately severe. Resource utilization
      associated with the number of days with fever, antibiotic use, and the number of
      transfusions administered was significantly higher after FH-CEM therapy than
      after SZ-Bu/Mel therapy. CONCLUSION: Use of autologous stem-cell transplantation
      is feasible in the context of a resource-limited country.

PMID- 30241256
TI  - Improving Immunohistochemistry Capability for Pediatric Cancer Care in the
      Central American and Caribbean Region: A Report From the AHOPCA Pathology Working
      Group.
AB  - Accessibility to immunohistochemistry (IHC) is invaluable to proper diagnosis and
      treatment of pediatric patients with malignant neoplasms. Whereas IHC is widely
      available in anatomic pathology laboratories in high-income countries, access to
      it in anatomic pathology laboratories of low- and middle-income countries remains
      a struggle, with many limitations. To advance the quality of the pathology
      service offered to children with cancer in areas with limited resources, a 5-day
      pathology training workshop was offered to pathologists and histotechnologists
      from various countries of the Central American and Caribbean region. An initial
      assessment of the workshop participants' current laboratory capacities was
      performed, and a regional training center was selected. Didactic and hands-on
      activities were offered, and review and evaluation of the IHC slides produced
      during the training course were compared with original slides from the
      participants' sites. This model of intensive 5-day training appears to be
      effective and can potentially be used in other budget-constrained regions.
      Moreover, it can serve as a continuing education activity for pathologists and
      histotechnologists, and as part of validations and quality improvement projects
      to build capacity and develop IHC assay proficiency in low- and middle-income
      countries.

PMID- 30241257
TI  - Impact of GI Tumor Board on Patient Management and Adherence to Guidelines.
AB  - PURPOSE: As the burden of cancer on the population and the health care system
      continues to increase with more complicated treatment options, the need for
      multidisciplinary teams to be as efficient as possible becomes more vital. Our
      study aimed to evaluate the consistency of GI Tumor Board (GI TB) recommendations
      with international guidelines, the adherence of physicians involved in patient
      care to TB recommendations, and the impact on the management of patients.
      METHODS: A prospective cohort study was conducted from January to June 2016 at
      our institution, which is a major tertiary hospital that provides comprehensive
      cancer care. All cases presented at the GI TB during this period were included.
      Data regarding adherence to National Comprehensive Cancer Network guidelines,
      adherence to TB recommendations, and changes made to the management of patients
      were collected weekly from the GI TB in a data collection form. RESULTS: Of the
      104 patients included, 57 (55%) were males and the median age was 58 (16 to 85)
      years. Colorectal cancer was the most common diagnosis, in 65 patients (63%).
      Nearly one-half of cases (45%) were stage IV cancers. Starting new treatment was
      recommended for 72 patients (69%). Further investigations were requested for 15
      patients (14%). For imaging, 24 recommendations (23%) were made. Adherence to
      National Comprehensive Cancer Network guidelines was observed in 97% of total
      recommendations. New findings were found in pathology (11%), radiology (13%), and
      staging (4%). Management plans were changed in 37 cases (36%). Over a 3-month
      period after presentation to the GI TB, most of the recommendations (87%) were
      performed. CONCLUSION: A multidisciplinary tumor board enhances the adherence to
      guidelines and has an impact on patient management in approximately one-third of
      patients. Among physicians, adherence to recommendations of the TB was high.

PMID- 30241258
TI  - Peer Mentoring at the Uganda Cancer Institute: A Novel Model for Career
      Development of Clinician-Scientists in Resource-Limited Settings.
AB  - Cancer centers are beginning to emerge in low- and middle-income countries
      despite having relatively few oncologists and specialists in related fields.
      Uganda, like many countries in sub-Saharan Africa, has a cadre of highly
      motivated clinician-scientists-in-training who are committed to developing the
      capacity for cancer care and research. However, potential local mentors for these
      trainees are burdened with uniquely high demands on their time for clinical care,
      teaching, institutional development, advocacy, and research. Facilitated peer
      mentoring helps to fill skills and confidence gaps and teaches mentoring skills
      so that trainees can learn to support one another and regularly access a more
      senior facilitator/role model. With an added consultant component, programs can
      engage limited senior faculty time to address specific training needs and to
      introduce junior investigators to advisors and even potential dyadic mentors. Two
      years after its inception, our facilitated peer mentoring career development
      program at the Uganda Cancer Institute in Kampala is successfully developing a
      new generation of researchers who, in turn, are now providing role models and
      mentors from within their group. This program provides a practical model for
      building the next generation of clinical scientists in developing countries.

PMID- 30241259
TI  - Facing the Global Challenges of Access to Cancer Medication.

PMID- 30241260
TI  - Patient Navigation and Access to Cancer Care in Guatemala.

PMID- 30241261
TI  - How Should Genetic Counseling for Ovarian Cancer Be Implemented in a Middle
      Income Country? An Insight Based on the Brazilian Scenario.

PMID- 30241262
TI  - Estimates of Cancer Incidence in Ethiopia in 2015 Using Population-Based Registry
      Data.
AB  - PURPOSE: Noncommunicable diseases, prominently cancer, have become the second
      leading cause of death in the adult population of Ethiopia. A population-based
      cancer registry has been used in Addis Ababa (the capital city) since 2011.
      Availability of up-to-date estimates on cancer incidence is important in guiding
      the national cancer control program in Ethiopia. METHODS: We obtained primary
      data on 8,539 patients from the Addis Ababa population-based cancer registry and
      supplemented by data on 1,648 cancer cases collected from six Ethiopian regions.
      We estimated the number of the commonest forms of cancer diagnosed among males
      and females in Ethiopia and computed crude and age-standardized incidence rates.
      RESULTS: For 2015 in Ethiopia, we estimated that 21,563 (95% CI, 17,416 to
      25,660) and 42,722 (95% CI, 37,412 to 48,040) incident cancer cases were
      diagnosed in males and females, respectively. The most common adult cancers were:
      cancers of the breast and cervix, colorectal cancer, non-Hodgkin lymphoma,
      leukemia, and cancers of the prostate, thyroid, lung, stomach, and liver.
      Leukemia was the leading cancer diagnosis in the pediatric age group (age 0 to 14
      years). Breast cancer was by far the commonest cancer, constituting 33% of the
      cancers in women and 23% of all cancers identified from the Addis Ababa cancer
      registry. It was also the commonest cancer in four of the six Ethiopian regions
      included in the analysis. Colorectal cancer and non-Hodgkin lymphoma were the
      commonest malignancies in men. CONCLUSION: Cancer, and more prominently breast
      cancer, poses a substantial public health threat in Ethiopia. The fight against
      cancer calls for expansion of population-based registry sites to improve
      quantifying the cancer burden in Ethiopia and requires both increased investment
      and application of existing cancer control knowledge across all segments of the
      Ethiopian population.

PMID- 30241263
TI  - Cost of Oncology Drugs in the Middle-Eastern Country of Lebanon: An Update (2014
      2016).
AB  - PURPOSE: This study aims to evaluate trends in the increasing costs of oncology
      drugs procured by the Lebanese Ministry of Public Health (MOPH) between 2014 and
      2016 and to assess the impact of the introduction in mid-2015 of new
      immunotherapy drugs for the treatment of lung cancer on the overall and specific
      costs of that treatment. METHODS: A secondary analysis of data from the MOPH
      Cancer Drug Scientific Committee data base was conducted using a total of 18,133
      cancer files between 2014 and 2016. RESULTS: Over the 3-year period, about $140
      million (USD) was spent on cancer drugs by the MOPH free cancer drug dispensing
      program. The expenditures increased by 27% after immunotherapy was phased in. The
      average cost of drugs per patient per year measured across all cancer types
      increased from $7,000 in 2014 to $8,400 in 2016. Trastuzumab, approved for
      treating human epidermal growth factor receptor 2-positive breast cancer ranked
      first in total expenditures for 2014-2015. By 2016, two new immunotherapy drugs
      had topped the list: pembrolizumab ranked first and nivolumab ranked third,
      representing 64% of the total cost of lung cancer treatment and approximately 19%
      of the total yearly budget; beneficiaries represented only 3% of all patients.
      CONCLUSION: This update documents the increasing financial impact of newer cancer
      drugs on the procurement process in the middle-income country of Lebanon. The
      trend is aligned with the financial burden of cancer drugs worldwide, which calls
      for a collaborative global response to this crisis.

PMID- 30241265
TI  - Toward the World Code Against Cancer.
AB  - Overwhelmed by an abundance of often confusing, ambiguous, or apparently
      contradictory messages on disease prevention in today's multiple media streams,
      the general public would surely value authoritative, clear, and evidence-based
      instructions on how to actively contribute to the reduction of their cancer risk.
      The European Code Against Cancer is a set of 12 recommendations for individuals
      on how to reduce cancer risk. The Code carries the authority and reliability of
      expert scientists working under the coordination of the International Agency for
      Research on Cancer, the cancer research agency of the WHO. The Code's messages
      are aimed at individuals and have been enthusiastically promoted by European
      cancer associations. The experience of developing and promoting the European Code
      has generated interest in developing analogous recommendations for other regions
      of the world. Under the overall umbrella of a World Code Against Cancer using the
      same International Agency for Research on Cancer methodology, regional Codes
      could be developed, focused on regions sufficiently large and distinct to merit
      development of versions adapted to regional differences in risk factors and
      cancer patterns. Consideration of such an adapted model illustrates why a simple
      translation of the European Code would not be sufficient to promote cancer
      prevention globally.

PMID- 30241264
TI  - Impact of HIV Infection on the Clinical Presentation and Survival of Non-Hodgkin
      Lymphoma: A Prospective Observational Study From Botswana.
AB  - PURPOSE: Botswana has a high prevalence of HIV infection. Currently, there are
      few data regarding the sociodemographic factors, clinical characteristics, and
      outcomes of non-Hodgkin lymphoma (NHL)-an AIDS-defining cancer-in the country.
      PATIENTS AND METHODS: This study used a prospective cancer registry to identify
      patients with a new diagnosis of NHL reporting for specialty cancer care at three
      hospitals in Botswana between October 2010 and August 2016. Treatment patterns
      and clinical outcomes were analyzed. RESULTS: One hundred four patients with a
      new diagnosis of NHL were enrolled in this study, 72% of whom had HIV infection.
      Compared with patients not infected with HIV, patients infected with HIV were
      younger (median age, 53.9 v 39.1 years; P = .001) and more likely to present with
      an aggressive subtype of NHL (65.5% v 84.0%; P = .008). All patients infected
      with HIV received combined antiretroviral therapy throughout the course of the
      study, and similar chemotherapeutic regimens were recommended for all patients,
      regardless of subtype or HIV status (six to eight cycles of cyclophosphamide,
      doxorubicin, vincristine, and prednisone; or cyclophosphamide, doxorubicin,
      vincristine, and prednisone plus rituximab). There was no difference in 1-year
      mortality among patients not infected with HIV and patients infected with HIV
      (unadjusted analysis, 52.9% v 37.1%; hazard ratio [HR], 0.73; P = .33; adjusted
      analysis, HR, 0.57; P = .14). However, when compared with a cohort of patients in
      the United States matched by subtype, stage, age, sex, and race, patients in
      Botswana fared worse (1-year mortality, 22.8% v 46.3%; HR, 1.89; P = .001).
      CONCLUSION: Among patients with NHL reporting for specialty cancer care in
      Botswana, there is no association between HIV status and 1-year survival.

PMID- 30241266
TI  - Is Fertility Preservation Feasible and Safe With Neoadjuvant Therapy for Breast
      Cancer?

PMID- 30241267
TI  - Oncology Guidelines Usage in a Low- and Middle-Income Country.
AB  - PURPOSE: There is a paucity of data about current usage of oncology guidelines in
      low- and middle-income countries (LMICs), specifically in terms of the
      availability and quality of those guidelines. Our objective was to determine
      usage of oncology guidelines and the barriers and facilitators to their usage
      among radiation oncologists in LMICs. METHODS: An online cross-sectional survey
      was conducted among practicing radiation oncologists in Nigeria via e-mail and
      the social media database of the Association of Radiation and Clinical
      Oncologists of Nigeria. In addition, paper questionnaires were administered at
      regional clinical meetings. RESULTS: The survey response rate was 53.4% in a
      sample of 101 radiation oncologists from the database. Sixty-nine percent of
      respondents were consultants and 30% were residents. Approximately 43% had < 5
      years' experience. All of the respondents were involved in administering
      chemotherapy during the treatment of patients with cancer, whereas approximately
      half were involved in diagnosing cancer. Ninety-three percent reported using
      guidelines in treating patients, the top two guidelines being those from the
      National Comprehensive Cancer Network (90%) and the American Society of Clinical
      Oncology (50%). The two major barriers to guideline usage were that facilities
      were inadequate for proper guideline implementation and that the information in
      guidelines were too complex to understand. Potential facilitators included
      providing adequate facilities, developing local guidelines, and increasing
      awareness of guideline usage. CONCLUSION: Our study shows that clinicians
      involved in the treatment of patients with cancer in LMICs are aware of cancer
      treatment guidelines. However, implementation of these guidelines hinders their
      usage because the facilities are inadequate, guidelines are not applicable to the
      local setting, and the information in the guidelines is too complex.

PMID- 30241268
TI  - Disparities in Breast, Lung, and Cervical Cancer Trials Worldwide.
AB  - PURPOSE: As cancer burden has risen worldwide, physicians, patients, and their
      advocates have become aware that the clinical cancer trial research paradigm is
      not ubiquitous. Furthermore, the number and characteristics of trials that are
      registered in low- and middle-income countries (LMICs) compared with that in high
      income countries (HICs) are unknown. METHODS: We collected retrospective data on
      trials for breast, lung, and cervical cancer registered in ClinicalTrials.gov or
      with the WHO International Clinical Trial Registry Platform between 2010 and
      2017. The data were then classified as trials within LMICs or HICs using
      definitions from the World Bank. RESULTS: Included in these analyses were 6,710
      trials, of which 3,164 (47%) were breast cancer trials, 3,283 (49%) were lung
      cancer trials, and 263 (4%) were cervical cancer trials. There were 1,951 (29%)
      trials from LMICs and 4,759 (71%) trials from HICs ( P < .001). Although the
      proportion of phase III trials in HICs versus LMICs was similar (18% v 17%; P =
      .66), the number of phase I trials in LMICs was significantly lower than that of
      HICs (20% v 2%; P < .001). For several LMICs with the highest mortality-to
      incidence ratios for breast, lung, or cervical cancer, there were no cancer
      trials registered in the registration data bases searched for this work.
      CONCLUSION: There are differences in access to cancer clinical trials in LMICs
      compared with HICs. Several factors, such as excessive cost and a lack of
      infrastructure and expertise, may explain these differences.

PMID- 30241269
TI  - Data Reliability and Coding Completeness of Cancer Registry Information Using
      Reabstracting Method in the National Cancer Institute: Thailand, 2012 to 2014.
AB  - PURPOSE: Data quality is a core value of cancer registries, which bring about
      greater understanding of cancer distribution and determinants. Thailand
      established its cancer registry in 1986; however, studies focusing on data
      reliability have been limited. This study aimed to assess the coding completeness
      and reliability of the National Cancer Institute (NCI) hospital-based cancer
      registry, Thailand. METHODS: This study was conducted using the reabstracting
      method. We focused on seven cancer sites-the colon, rectum, liver, lung, breast,
      cervix, and prostate-registered between 2012 and 2014 in the NCI hospital-based
      cancer registry. Missing data were identified for coding completeness calculation
      among important variables. The agreement rate and kappa coefficient were computed
      to represent data reliability. RESULTS: For reabstracting, we retrieved 957
      medical records from a total of 5,462. These were selected using the probability
      proportional to size method, stratified by topology, sex, and registered year.
      The overall coding completeness of the registered and reabstracted data was 89.9%
      and 93.6%, respectively. In addition, the overall agreement rate among variables
      ranged from 84.7% to 99.6%, and kappa coefficient ranged from 0.619 to 0.995. The
      misclassification among unilateral organs caused lower coding completeness and
      agreement rate of laterality coding. The completeness of current residency could
      be improved using the reabstracting method. The lowest agreement rate was found
      among various categories of diagnosis basis. Sex misclassification for male
      breast cancer was identified. CONCLUSION: The coding completeness and data
      reliability of the NCI hospital-based cancer registry met the standard in most
      critical variables. However, some challenges remain to improve the data quality.
      The reabstracting method could identify the critical points affecting the quality
      of cancer registry data.

PMID- 30241270
TI  - ASCO Leadership Development Program: International Perspectives.

PMID- 30241271
TI  - Analgesic Prescription Patterns and Pain Outcomes in Southeast Asia: Findings
      From the Analgesic Treatment of Cancer Pain in Southeast Asia Study.
AB  - PURPOSE: To identify patterns of analgesic prescription and to explore patient
      reported pain intensity, sleep disturbance, and quality of life among cancer
      patients with pain in Southeast Asia (SEA). METHODS: This cross-sectional
      observational study included 465 adult outpatients prescribed analgesics for
      cancer pain for 1 month or longer at 22 sites in Indonesia, Malaysia,
      Philippines, Singapore, Thailand, and Vietnam. Data on analgesic prescription and
      cancer characteristics were extracted from medical records. Pain intensity, sleep
      disturbance, and quality of life measures were recorded via questionnaires.
      RESULTS: Most patients (84.4%) had stage III or IV cancer. A total of 419
      patients (90.7%) were prescribed opioids; of these, 42.2% received only weak
      opioids, whereas 57.8% received at least one strong opioid. The mean worst pain
      intensity during the past 24 hours was 4.76 (standard deviation [SD], 2.47) on a
      scale of 0 (no pain) to 10 (worst possible pain); the mean current pain intensity
      was 4.10 (SD, 2.61). More than half of patients (54.8%) reported sleep
      disturbance caused by pain in the past 7 days. The majority of patients reported
      problems with pain/discomfort (82.3%), usual activities (65.8%), mobility
      (58.2%), and anxiety/depression (56.3%). The median daily dose prescribed in oral
      morphine equivalents was 30 mg for both morphine and tramadol. CONCLUSION:
      Despite unrelieved pain, sleep disturbance, and issues with quality of life, a
      notable proportion of patients were prescribed only weak opioids, and opioid
      doses prescribed were generally low. Efforts focused on encouragement of
      prescriptions with analgesic strength and/or doses proportional to the pain
      management needs of patients are vital to improve the status of cancer pain
      management in the region.

PMID- 30241272
TI  - Financial Impact of Complex Cancer Surgery in India: A Study of Pancreatic
      Cancer.
AB  - PURPOSE: The rapidly increasing burden of cancer in India has profound impacts on
      health care costs for patients and their families. High out-of-pocket (OOP)
      expenditure, lack of insurance, and low government expenditure create a vicious
      cycle, leading to household impoverishment. Complex cancer surgery is now
      increasingly important for emerging countries; however, little is understood
      about the macro- and microeconomics of these procedures. After the Lancet
      Oncology Commission on Global Cancer Surgery, we evaluated the OOP expenditure
      for patients undergoing pancreatico-duodenectomy (PD) at a government tertiary
      cancer center in India. METHODS: Prospective data from 98 patients who underwent
      PD between January 2014 and June 2015 were collected and analyzed. The time frame
      for consideration of expenses, including all preoperative investigations, was
      from the first hospital visit to the day of discharge. Catastrophic expenditure
      was calculated by assessing the percentage of households in which OOP health
      payments exceeded 10% of the total household income. RESULTS: The mean
      expenditure for PD by patients was Rs.295,679.57 (US$74,420, purchasing power
      parity corrected). This amount was significantly higher among those admitted to a
      private ward and those with complications. Only 29.6% of the patients had
      insurance coverage. A total of 76.5% of the sample incurred catastrophic
      expenditure, and 38% of those with insurance underwent financial catastrophe
      compared with 93% of those without insurance. The percentage of patients facing
      catastrophic impact was highest among those in semiprivate wards, at 86.7%,
      followed by those in public and private wards. CONCLUSION: The cost of PD is high
      and is often unaffordable for a majority of India's population. A review of
      insurance coverage policies for better coverage must be considered.

PMID- 30241273
TI  - Evidence From Ghana Indicates That Childhood Cancer Treatment in Sub-Saharan
      Africa Is Very Cost Effective: A Report From the Childhood Cancer 2030 Network.
AB  - PURPOSE: No published study to date has examined total cost and cost
      effectiveness of maintaining a pediatric oncology treatment center in an African
      setting, thus limiting childhood cancer advocacy and policy efforts. METHODS:
      Within the Korle Bu Teaching Hospital in Accra, Ghana, costing data were gathered
      for all inputs related to operating a pediatric cancer unit. Cost and volume data
      for relevant clinical services (eg, laboratory, pathology, medications) were
      obtained retrospectively or prospectively. Salaries were determined and
      multiplied by proportion of time dedicated toward pediatric patients with cancer.
      Costs associated with inpatient bed use, outpatient clinic use, administrative
      fees, and overhead were estimated. Costs were summed for a total annual operating
      cost. Cost-effectiveness was calculated based on annual patients with newly
      diagnosed disease, survival rates, and life expectancy. RESULTS: The Korle Bu
      Teaching Hospital pediatric cancer unit treats on average 170 new diagnoses
      annually. Total operating cost was $1.7 million/y. Personnel salaries and
      operating room costs were the most expensive inputs, contributing 45% and 21% of
      total costs. Together, medications, imaging, radiation, and pathology services
      accounted for 7%. The cost per disability-adjusted life-year averted was $1,034,
      less than the Ghanaian per capita income, and thus considered very cost effective
      as per WHO-CHOICE methodology. CONCLUSION: To our knowledge, this study is the
      first to examine institution-level costs and cost-effectiveness of a childhood
      cancer program in an African setting, demonstrating that operating such a program
      in this setting is very cost effective. These results will inform national
      childhood cancer strategies in Africa and other low- and middle-income country
      settings.

PMID- 30241274
TI  - Oncologic and Palliative Care in a Global Setting in the Twenty-First Century:
      The Patient, Family, and Oncologic Health Care Team.

PMID- 30241275
TI  - Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A
      Comparative Study From Sudan.
AB  - PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse
      effect. Neurokinin-1 receptor antagonist (NK1RA)-containing regimens are the
      standard regimens for CINV prophylaxis in patients with cancer receiving highly
      or moderately emetogenic chemotherapy (HEC or MEC). NK1RA agents are expensive
      and were not registered in Sudan. Recently, regimens containing olanzapine, the
      available and affordable medication in Sudan, were introduced as another option.
      This study aimed to compare the efficacy of an olanzapine-containing regimen with
      the antiemetic regimen that was currently used in our institute for CINV
      prophylaxis in HEC/MEC settings. PATIENTS AND METHODS: The study prospectively
      compared an olanzapine-containing regimen (acute phase: olanzapine, ondansetron,
      dexamethasone; delayed phase: olanzapine, ondansetron) with an
      ondansetron/dexamethasone regimen (acute phase: ondansetron, dexamethasone;
      delayed phase: ondansetron) in adult patients with cancer receiving HEC or MEC.
      The study outcomes were complete response (CR; no emesis and no rescue
      medications) and nausea control (no nausea), which were assessed in the acute (0
      to 24 hours), delayed (24 to 120 hours), and overall (0 to 120 hours) phases.
      RESULTS: The study included 131 patients (olanzapine-containing: 50 patients;
      ondansetron/dexamethasone: 81 patients). CR and nausea control were higher in the
      olanzapine-containing than in the ondansetron/dexamethasone regimen (CR: acute
      phase, 86% v 71.6%; P = .086; delayed phase, 72% v 30.9%; P < .001; overall
      phase, 66% v 25.9%; P < .001; nausea control: acute phase, 86% v 74.1%; P = .127;
      delayed phase, 76% v 34.6%; P < .001; overall phase, 72% v 29.6%; P < .001). The
      major toxicity of olanzapine was grade 1 and 2 sedation or drowsiness (25
      patients). CONCLUSION: An olanzapine-containing regimen has better efficacy for
      prevention of CINV in the HEC/MEC setting. Oncologists working in a limited
      resource setting should be familiar with olanzapine-containing regimens, because
      NK1RA agents are not affordable and not easily available.

PMID- 30241276
TI  - Stage III Non-Small-Cell Lung Cancer Treated With Concurrent Chemoradiation
      Followed or Not by Consolidation Chemotherapy: A Survival Analysis From a
      Brazilian Multicentric Cohort.
AB  - PURPOSE: Of newly diagnosed patients with non-small-cell lung cancer (NSCLC),
      stage III accounts for 30%. Most patients are treated with concurrent
      chemoradiation therapy, but the addition of consolidation chemotherapy (CC) is
      debatable. We examined the effect of CC in Brazilian patients with stage III
      NSCLC treated in routine clinical practice. METHODS: We retrospectively collected
      data for patients from five different Brazilian cancer institutions who had stage
      III NSCLC and who were treated with chemoradiation therapy followed or not by CC.
      Eligible patients were age 18 years or older and must have been treated with
      cisplatin-carboplatin plus etoposide, paclitaxel, or vinorelbine, concurrently
      with thoracic radiation therapy (RT). Patients treated with surgery or
      neoadjuvant chemotherapy were excluded. The primary end point was overall
      survival (OS). Associations between CC and clinical variables and demographics
      were evaluated by using Pearson's chi2 test. Survival curves were calculated by
      using the Kaplan-Meier method and were compared using the log-rank test.
      Univariable and multivariable analysis used a Cox proportional hazards model.
      RESULTS: We collected data from 165 patients. Median age was 60 years. Most
      patients were male (69.1%), white (77.9%), current or former smokers (93.3%), and
      had stage IIIB disease (52.7%). Adenocarcinoma was the most common histology
      (47.9%). Weight loss of more than 5% was observed in 39.1% and Eastern
      Cooperative Oncology Group performance status of 2 was observed in 14.6%. The
      only variable associated with CC was T stage ( P = .022). We observed no
      statistically significant difference in OS between patients treated or not with
      CC ( P = .128). A total delivered RT dose >= 61 Gy was the only variable
      independently associated with improved survival ( P = .012). CONCLUSION:
      Brazilian patients with locally advanced NSCLC who were treated with standard
      treatment achieved OS similar to that reported in randomized trials. CC did not
      improve OS in patients with stage III NSCLC after concurrent chemoradiation
      therapy. An RT dose of less than 61 Gy had a negative effect on OS.

PMID- 30241277
TI  - Outcome of Patients With Breast Cancer Treated in a Private Health Care
      Institution in Brazil.
AB  - PURPOSE: Middle-income countries like Brazil often have a dichotomous health care
      system in which patients may be treated in either public or private institutions
      that differ substantially in terms of level of access to diagnostic and
      therapeutic procedures. PATIENTS AND METHODS: This was a prospective,
      observational study to assess real-world data in 1,230 female patients with
      breast cancer who were treated in a private health care institution between 2012
      and 2016 in Brazil. RESULTS: Breast cancer in these patients mostly was diagnosed
      at early (79.0% stages I or II) or locally advanced (16.1% stage III) stages. The
      primary tumor was resected in 89.0% of cases, most often through breast
      conserving surgery (55.1%). Patients with locally advanced disease received more
      aggressive therapy (eg, higher rates of mastectomy, axillary dissection and
      chemotherapy use) than patients with early-stage disease. The estimated 2-year
      overall survival (OS) was 95.3%. Survival was significantly longer among patients
      with stage I or II disease (2-year OS, 97.9% and 97.5%, respectively) than those
      with stage III or IV disease (89.4% and 69.5%, respectively; P < .01). Tumor
      grade was also correlated with OS in the overall cohort ( P = .05); triple
      negative status was only prognostic for patients with stage III disease ( P <
      .01). CONCLUSION: The data provided aid understanding of the current scenario of
      breast cancer presentation and treatment in the Brazilian private health care
      system and may serve as a foundation to guide resource allocation. Our results
      reinforce the need to pursue adequate access to cancer care in low- and middle
      income countries to optimize patient outcome.

PMID- 30241278
TI  - Establishing a Pediatric Hematology-Oncology Program in Botswana.
AB  - PURPOSE: Annually, 300,000 children are diagnosed with cancer, and the majority
      of these children live in low- and middle-income countries (LMICs). Currently,
      there is incomplete information on pediatric cancer incidence, diagnosis
      distribution, and treatment outcomes in Africa. Since 2007, a pediatric
      hematology-oncology program has been operating in Botswana through a partnership
      between the Botswana government, Baylor College of Medicine, and Texas Children's
      Hospital. METHODS: To better understand patient characteristics and outcomes at
      Botswana's only pediatric cancer program, a hospital-based data base-the Botswana
      Pediatric Oncology Database-was established in 2014. Children younger than 18
      years of age at the time of diagnosis who presented between 2008 and 2015 were
      included. Data for this study were extracted in February 2016. RESULTS: Of the
      240 potential enrollees, 185 (77%) children met eligibility for this study. The
      median age was 6.4 years, and 50.8% were male. Leukemia was the most common
      malignancy representing 18.9% of the cohort and 88.1% of the total cohort had a
      histopathologic diagnosis. HIV seropositivity was confirmed in 13.5%. The 2-year
      overall survival of all pediatric cancer diagnoses was 52.4%. Abandonment of
      treatment occurred in 3.8% of patients. CONCLUSION: In the first 9 years of the
      program, capacity has been developed through a longstanding partnership between
      Botswana and Baylor College of Medicine/Texas Children's Hospital that has led to
      children receiving care for cancer and blood disorders. Although continued
      improvements are necessary, outcomes to date indicate that children with cancer
      in Botswana can be successfully diagnosed and treated.

PMID- 30241279
TI  - New Digital Plug and Imaging Sensor for a Proton Therapy Monitoring System Based
      on Positron Emission Tomography.
AB  - One of the most challenging areas of sensor development for nuclear medicine is
      the design of proton therapy monitoring systems. Sensors are operated in a high
      detection rate regime in beam-on conditions. We realized a prototype of a
      monitoring system for proton therapy based on the technique of positron emission
      tomography. We used the Plug and Imaging (P&I) technology in this application.
      This sensing system includes LYSO/silicon photomultiplier (SiPM) detection
      elements, fast digital multi voltage threshold (MVT) readout electronics and
      dedicated image reconstruction algorithms. In this paper, we show that the P&I
      sensor system has a uniform response and is controllable in the experimental
      conditions of the proton therapy room. The prototype of PET monitoring device
      based on the P&I sensor system has an intrinsic experimental spatial resolution
      of approximately 3 mm (FWHM), obtained operating the prototype both during the
      beam irradiation and right after it. The count-rate performance of the P&I sensor
      approaches 5 Mcps and allows the collection of relevant statistics for the
      nuclide analysis. The measurement of both the half life and the relative
      abundance of the positron emitters generated in the target volume through
      irradiation of 10 10 protons in approximately 15 s is performed with 0.5% and 5 %
      accuracy, respectively.

PMID- 30241281
TI  - Support Vector Regression Approach to Predict the Design Space for the Extraction
      Process of Pueraria lobata.
AB  - A support vector regression (SVR) method was introduced to improve the robustness
      and predictability of the design space in the implementation of quality by design
      (QbD), taking the extraction process of Pueraria lobata as a case study. In this
      paper, extraction time, number of extraction cycles, and liquid-solid ratio were
      identified as critical process parameters (CPPs), and the yield of puerarin,
      total isoflavonoids, and extracta sicca were the critical quality attributes
      (CQAs). Models between CQAs and CPPs were constructed using both a conventional
      quadratic polynomial model (QPM) and the SVR algorithm. The results of the two
      models indicated that the SVR model had better performance, with a higher R2 and
      lower root-mean-square error (RMSE) and mean absolute deviation (MAD) than those
      of the QPM. Furthermore, the design space was predicted using a grid search
      technique. The operational range was extraction time, 24-51 min; number of
      extraction cycles, 3; and liquid-solid ratio, 14-18 mL/g. This study is the first
      reported work optimizing the design space of the extraction process of P. lobata
      based on an SVR model. SVR modeling, with its better prediction accuracy and
      generalization ability, could be a reliable tool for predicting the design space
      and shows great potential for the quality control of QbD.

PMID- 30241280
TI  - Molecular Cloning of the B4GALNT2 Gene and Its Single Nucleotide Polymorphisms
      Association with Litter Size in Small Tail Han Sheep.
AB  - A new fecundity gene named the FecL (mutation), which regulates the ovulation
      rate, was discovered in French Lacaune sheep. The B4GALNT2 (beta-1, 4-N-acetyl
      galactosaminyl transferase 2) gene was considered as the potential FecL mutation
      gene. This study explores whether the effect of the FecL mutation exists in other
      sheep breeds, and the features of the B4GALNT2 gene in terms of the molecular
      structure and its expression profile. Using Sanger sequencing, we found that high
      and low fecundity breeds from among 11 measured sheep breeds all had no variation
      in the three specific mutation sites, which were linked with the FecL mutation.
      However, two mutations of g.36946470C > T and g.36933082C > T in the exon of
      B4GALNT2 had a significant effect on litter size in the first parity for Small
      Tail Han (STH) Sheep (p < 0.05). Two transcription start sites (TSS) of B4GALNT2
      in its 5'-flanking region were discovered in ovine granule cells in vitro,
      through the RACE (Rapid amplification of cDNA ends) method. Except for in the
      kidney and oviduct, no significant difference in expression levels had been found
      between STH sheep and Tan sheep breeds. The B4GALNT2 gene, as a candidate for
      FecL, may have a relationship with the differences in litter size in STH sheep.
      B4GALNT2 is mainly expressed in the ovine ovary, which also suggests that
      B4GALNT2 plays an important role in sheep reproduction.

PMID- 30241282
TI  - Cysteine Proteases from V. cundinamarcensis (C. candamarcensis) Inhibit Melanoma
      Metastasis and Modulate Expression of Proteins Related to Proliferation,
      Migration and Differentiation.
AB  - Previous studies showed that P1G10, a proteolytic fraction from Vasconcellea
      cundinamarcensis latex, reduced the tumor mass in animals bearing melanoma,
      increased in vitro DNA fragmentation and decreased cell adhesion. Here, we
      present some molecular and cellular events related to the antimetastatic effect
      induced by the CMS-2 fraction derived from P1G10 in metastatic melanoma B16-F10
      and melanocyte Melan-a. Using difference gel electrophoresis and mass
      spectrometry, we identified four proteins overexpressed in tumor cells, all of
      them related to proliferation, survival, migration and cell invasion, that had
      their expression normalized upon treatment with CMS-2: nucleophosmin 1, heat
      shock protein 65, calcyclin binding protein and eukaryotic translation initiation
      factor 4H. In addition, some antioxidant and glycolytic enzymes show increased
      expression after exposure to CMS-2, along with an induction of melanogenesis
      (differentiation marker). The down regulation of cofilin 1, a protein involved in
      cell motility, may explain the inhibition of cell migration and dendritic-like
      outgrowth in B16-F10 and Melan-a, observed after CMS-2 treatment. Taken together,
      it is argued that CMS-2 modulates the expression of proteins related to
      metastatic development, driving the cell to a more differentiated-like state.
      These effects support the CMS-2 antimetastatic activity and place this fraction
      in the category of anticancer agent.

PMID- 30241283
TI  - Synthesis and Comparative Biological Properties of Ag-PEG Nanoparticles with
      Tunable Morphologies from Janus to Multi-Core Shell Structure.
AB  - Silver nanoparticles synthesized with polymers as coating agents is an effective
      method to overcome their poor stability and aggregation in solution. Silver
      polyethylene glycol (Ag-PEG) nanoparticles were synthesized with the thiol
      functionalized polyethylene glycol (SH-PEA) as the coating, reducing and
      stabilizing agent. The UV irradiation time, polymer and silver nitrate
      concentration for the synthesis were investigated. The concentration of silver
      nitrate had significant effect on the morphology of Ag-PEG nanoparticles. When
      increasing the concentration of silver nitrate, SEM and TEM images showed that Ag
      PEG nanoparticles changed from Janus to multi-core shell structure. Meanwhile,
      pure silver particles in the two hybrid nanoparticles presented spherical shape
      and had the similar size of 15 nm. The antibacterial activities and cytotoxicity
      of the two structural Ag-PEG nanoparticles were investigated to understand
      colloid morphology effect on the properties of AgNPs. The results of
      antibacterial activities showed that the two structural Ag-PEG nanoparticles
      exhibited strong antibacterial activities against Staphylococcus aureus,
      Escherichia coli and Bacillus subtilis. The Janus nanoparticles had larger
      minimal inhibitory concentration (MIC) and minimum bacterial concentration (MBC)
      values than the multi-core shell counterparts. The results of cytotoxicity showed
      the Janus Ag-PEG nanoparticles had lower toxicity than the multi-core shell
      nanoparticles.

PMID- 30241287
TI  - Integrin-Mediated Delivery of Drugs and Nucleic Acids for Anti-Angiogenic Cancer
      Therapy: Current Landscape and Remaining Challenges.
AB  - Angiogenesis, sprouting of new blood vessels from pre-existing vasculatures,
      plays a critical role in regulating tumor growth. Binding interactions between
      integrin, a heterodimeric transmembrane glycoprotein receptor, and its
      extracellular matrix (ECM) protein ligands govern the angiogenic potential of
      tumor endothelial cells. Integrin receptors are attractive targets in cancer
      therapy due to their overexpression on tumor endothelial cells, but not on
      quiescent blood vessels. These receptors are finding increasing applications in
      anti-angiogenic therapy via targeted delivery of chemotherapeutic drugs and
      nucleic acids to tumor vasculatures. The current article attempts to provide a
      retrospective account of the past developments, highlight important contemporary
      contributions and unresolved set-backs of this emerging field.

PMID- 30241284
TI  - Ebola Virus Causes Intestinal Tract Architectural Disruption and Bacterial
      Invasion in Non-Human Primates.
AB  - In the 2014-2016 West Africa Ebola Virus (EBOV) outbreak, there was a significant
      concern raised about the potential for secondary bacterial infection originating
      from the gastrointestinal tract, which led to the empiric treatment of many
      patients with antibiotics. This retrospective pathology case series summarizes
      the gastrointestinal pathology observed in control animals in the rhesus EBOV
      Kikwit intramuscular 1000 plaque forming unit infection model. All 31 Non-human
      primates (NHPs) exhibited lymphoid depletion of gut-associated lymphoid tissue
      (GALT) but the severity and the specific location of the depletion varied.
      Mesenteric lymphoid depletion and necrosis were present in 87% (27/31) of NHPs.
      There was mucosal barrier disruption of the intestinal tract with mucosal
      necrosis and/or ulceration most notably in the duodenum (16%), cecum (16%), and
      colon (29%). In the intestinal tract, hemorrhage was noted most frequently in the
      duodenum (52%) and colon (45%). There were focal areas of bacterial submucosal
      invasion in the gastrointestinal (GI) tract in 9/31 (29%) of NHPs. Only 2/31 (6%)
      had evidence of pancreatic necrosis. One NHP (3%) experienced jejunal
      intussusception which may have been directly related to EBOV. Immunofluorescence
      assays demonstrated EBOV antigen in CD68+ macrophage/monocytes and endothelial
      cells in areas of GI vascular injury or necrosis.

PMID- 30241286
TI  - Segmentation-Based Color Channel Registration for Disparity Estimation of Dual
      Color-Filtered Aperture Camera.
AB  - Single-lens-based optical range finding systems were developed as an efficient,
      compact alternative for conventional stereo camera systems. Among various single
      lens-based approaches, a multiple color-filtered aperture (MCA) system can
      generate disparity information among color channels, as well as normal color
      information. In this paper, we consider a dual color-filtered aperture (DCA)
      system as the most minimal version of the MCA system and present a novel inter
      color image registration algorithm for disparity estimation. This proposed
      registration algorithm consists of three steps: (i) color channel independent
      feature extraction; (ii) feature-based adaptive weight disparity estimation; and
      (iii) color mapping matrix (CMM)-based cross-channel image registration.
      Experimental results show that the proposed method can not only generate an
      accurate disparity map, but also realize high quality cross-channel registration
      with a disparity prior for DCA-based range finding and color image enhancement.

PMID- 30241285
TI  - Enhancement of Cell Adhesion, Cell Growth, Wound Healing, and Oxidative
      Protection by Gelatins Extracted from Extrusion-Pretreated Tilapia (Oreochromis
      sp.) Fish Scale.
AB  - Gelatin has been broadly utilized in the food, pharmaceutical, photographic,
      cosmetic and packaging industries, and there is also huge potential for novel
      applications of gelatin in the fields of biotechnology and biomedicine. In the
      present study, we extracted gelatin from fish processing waste, i.e., scale of
      tilapia, by a combined method of extrusion-pretreatment and hot water extraction.
      The extrusion-pretreatment process increases the extraction yield of gelatin.
      Three gelatins (FS2: preconditioning with double-distilled water (ddH2O) before
      extrusion; FS12: preconditioning with citric acid solution before extrusion;
      FS14: preconditioning with acetic acid solution before extrusion) were obtained
      and all of them enhanced cell adhesion, cell growth, and wound healing in HaCaT
      cells and protected HaCaT cells from H2O2-induced cellular damage. Among FS2,
      FS12, and FS14, FS12 exhibited the most pronounced enhancement of cell adhesion,
      cell growth, and wound healing in HaCaT cells, and thus it may have potential as
      an effective natural raw material in cell therapies for cutaneous wounds and for
      reducing H2O2-induced oxidative damage of cells. In additional experiments, it
      was found that phosphorylations of Akt and mTOR are involved in the signaling
      pathway activated by FS2, FS12, and FS14 in HaCaT cells.

PMID- 30241288
TI  - Wetting Transitions of Liquid Gallium Film on Nanopillar-Decorated Graphene
      Surfaces.
AB  - Molecular dynamics (MD) simulation has been employed to study the wetting
      transitions of liquid gallium droplet on the graphene surfaces, which are
      decorated with three types of carbon nanopillars, and to explore the effect of
      the surface roughness and morphology on the wettability of liquid Ga. The
      simulation results showed that, at the beginning, the Ga film looks like an
      upside-down dish on the rough surface, different from that on the smooth graphene
      surface, and its size is crucial to the final state of liquid. Ga droplets
      exhibit a Cassie-Baxter (CB) state, a Wenzel state, a Mixed Wetting state, and a
      dewetting state on the patterned surfaces by changing distribution and the
      morphology of nanopillars. Top morphology of nanopillars has a direct impact on
      the wetting transition of liquid Ga. There are three transition states for the
      two types of carbon nanotube (CNT) substrates and two for the carbon nanocone
      (CNC) one. Furthermore, we have found that the substrates show high or low
      adhesion to the Ga droplet with the variation of their roughness and top
      morphology. With the roughness decreasing, the adhesion energy of the substrate
      decreases. With the same roughness, the CNC/graphene surface has the lowest
      adhesion energy, followed by CNT/graphene and capped CNT/graphene surfaces. Our
      findings provide not only valid support to previous works but also reveal new
      theories on the wetting model of the metal droplet on the rough substrates.

PMID- 30241289
TI  - Promoting a Healthy Diet in Young Adults: The Role of Nutrition Labelling.
AB  - The use of the nutrition facts label has been associated with healthy eating
      behaviors for adults. However, the relationship between nutrition facts label use
      and overall diet quality is not well known in young adults, a vulnerable group
      that acquire lifelong eating behaviors during this period of life. This study
      aimed to assess if the use of information on the nutrition facts label is
      associated with a higher diet quality in young adults. In this cross-sectional
      study, 958 university students aged 18-34 years were recruited. Nutrition facts
      label use was recorded. Dietary intake was assessed using 24-h dietary recall.
      Healthy Eating Index-2005 (HEI-2005) scores were calculated. HEI-2005 score was
      significantly associated with using nutrition facts label (p < 0.001). The mean
      total HEI-2005 score was 60.7 +/- 10.11, 62.4 +/- 11.43 and 67.1 +/- 12.23
      respectively for never, sometimes and everytime users of nutrition facts label (p
      < 0.001). Sub-group scores of HEI-2005 for total fruits, whole fruits, total
      vegetables, whole grains, milk, oils, saturated fat, and calories from solid fat,
      alcohol and added sugar (SoFAAS) were significantly higher in regular nutrition
      facts label users (p < 0.05, for each). This study showed that young adults who
      regularly use the nutrition facts label have a higher diet quality.

PMID- 30241290
TI  - Electrospun Poly(ethylene-co-vinyl alcohol)/Graphene Nanoplatelets Composites of
      Interest in Intelligent Food Packaging Applications.
AB  - Graphene nanoplatelets (GNPs) were synthetized from graphite powder and,
      thereafter, embedded in poly(ethylene-co-vinyl alcohol) (EVOH) fibers by
      electrospinning in the 0.1-2 wt.-% range. The morphological, chemical, and
      thermal characterization performed on the electrospun nanocomposite fibers mats
      revealed that the GNPs were efficiently dispersed and rolled along the EVOH
      fibrilar matrix up to contents of 0.5 wt.-%. Additionally, the dielectric
      behavior of the nanocomposite fibers was evaluated as a function of the frequency
      range and GNPs content. The obtained results indicated that their dielectric
      constant rapidly decreased with the frequency increase and only increased at low
      GNPs loadings while the nanocomposite fiber mats became electrically conductive,
      with the maximum at 0.5 wt.-% GNPs content. Finally, the electrospun mats were
      subjected to a thermal post-treatment and dark films with a high contact
      transparency were obtained, suggesting that the nanocomposites can be used either
      in a nonwoven fibers form or in a continuous film form. This study demonstrates
      the potential of electrospinning as a promising technology to produce GNPs
      containing materials with high electrical conductivity that can be of potential
      interest in intelligent packaging applications as "smart" labels or tags.

PMID- 30241291
TI  - Perceptions about the Federally Mandated Smoke-Free Housing Policy among
      Residents Living in Public Housing in New York City.
AB  - Background: To assess residents' attitudes towards the United States (U.S.)
      Department of Housing and Urban Development's new smoke-free public housing
      policy, perceptions about barriers to policy implementation, and suggestions for
      optimizing implementation. Methods: In 2017, we conducted 10 focus groups among
      91 residents (smokers and nonsmokers) living in New York City public housing.
      Results: Smokers and nonsmokers expressed skepticism about the public housing
      authority's capacity to enforce the policy due to widespread violations of the
      current smoke-free policy in common areas and pervasive use of marijuana in
      buildings. Most believed that resident engagement in the roll-out and providing
      smoking cessation services was important for compliance. Resident expressed
      concerns about evictions and worried that other building priorities (i.e.,
      repairs, drug use) would be ignored with the focus now on smoke-free housing.
      Conclusions: Resident-endorsed strategies to optimize implementation
      effectiveness include improving the access to cessation services, ongoing
      resident engagement, education and communication to address misconceptions and
      concerns about enforcement, and placing smoke-free homes in a larger public
      housing authority healthy housing agenda.

PMID- 30241293
TI  - CdS/CdTe Heterostructures for Applications in Ultra-Thin Solar Cells.
AB  - The preparation of ultra-thin semi-transparent solar cells with potential
      applications in windows or transparent roofs entails several challenges due to
      the very small thickness of the layers involved. In particular, problems related
      to undesired inter-diffusion or inhomogeneities originated by incomplete coverage
      of the growing surfaces must be prevented. In this paper, undoped SnO2, CdS, and
      CdTe thin films with thickness suitable for use in ultra-thin solar cells were
      deposited with a radiofrequency (RF) magnetron sputtering technique onto
      conductive glass. Preparation conditions were found for depositing the individual
      layers with good surface coverage, absence of pin holes and with a relatively
      small growth rate adapted for the control of very small thickness. After a
      careful growth calibration procedure, heterostructured solar cells devices were
      fabricated. The influence of an additional undoped SnO2 buffer layer deposited
      between the conductive glass and the CdS window was studied. The incorporation of
      this layer led to an enhancement of both short circuit current and open circuit
      voltage (by 19 and 32%, respectively) without appreciable changes of other
      parameters. After the analysis of the cell parameters extracted from the current
      voltage (I-V) curves, possible origins of these effects were found to be:
      Passivation effects of the SnO2/CdS interface, blocking of impurities diffusion
      or improvement of the band alignment.

PMID- 30241292
TI  - Interactions between Bitter Taste, Diet and Dysbiosis: Consequences for Appetite
      and Obesity.
AB  - The type 2 family of taste receptors (T2Rs) detect and respond to bitter
      tastants. These receptors are expressed throughout the gastrointestinal (GI)
      tract, with location dependant roles. In the oral cavity, T2Rs are involved in
      the conscious perception of bitter tastants, while in the lower GI tract they
      have roles in chemoreception and regulation of GI function. Through these diverse
      roles, these receptors may be involved in modulating appetite and diet, with
      consequences for weight regulation and obesity. Interestingly, the concentration
      of T2Rs in the GI tract is greatest in the large intestine, the organ with the
      densest colonisation of bacteria. The gut microbiome has been the subject of
      intense research, as a plethora of roles linking microbiota to human health
      continue to be uncovered. Of particular interest is the microbial signature
      associated with obesity. Obesity is a leading health concern, and advances in our
      understanding of this disease are needed. Diet is a known modifiable factor in
      the development of obesity. However, diet only partially explains disease risk.
      Changes in microbial energy harvesting by the microbiota plays a role in obesity,
      and the composition of these energy harvesting populations may be controlled by
      taste receptors. This review explores T2Rs as a potential link between obesity
      and the human GI microbiome.

PMID- 30241294
TI  - Occupational Health Risk Assessment in the Electronics Industry in China Based on
      the Occupational Classification Method and EPA Model.
AB  - The awareness of occupational health risk management in the electronics industry
      is weak in China, and many Chinese occupational health management regulations
      have not been effectively implemented. China's current occupational hazards
      classification method and the Environmental Protection Agency (EPA) inhalation
      risk assessment model recognized internationally were used to perform health risk
      assessments for a chip manufacturing company in the electronics industry in order
      to determine the existing problems and put forward the optimization proposals of
      the occupational hazards classification method in China. The results showed that
      the detected concentrations of toxic and harmful chemicals in all testing points
      did not exceed the occupational health exposure limits in China. According to the
      EPA inhalation risk assessment model, the highest values of non-carcinogenic
      risks of ammonia, chlorine, fluoride, sulfuric acid, hydrogen chloride, ethylene
      glycol, phosphine, boron trifluoride, isopropanol, benzene, and xylene were 5.10,
      67.12, 1.71, 45.98, 1.83, 1.43, 160.35, 46.56, 2.52, 5.55, and 5.37,
      respectively, which means workers in electronic chip manufacturing companies
      exposed to these chemicals have higher occupational health risks. However, on the
      basis of the occupational hazards classification method, the occupational health
      risks of exposure to the toxic and hazardous chemicals are relatively harmless
      operations. The evaluation results of the EPA inhalation risk assessment model
      are generally higher than those of the occupational hazards classification
      method. It's recommended to refine the value of occupational exposure limit B,
      taking more characteristics of the hazard factors into account and fuzzifying the
      parameters to optimize the occupational hazards classification method. At the
      same time, it is suggested that the electronic chip manufacturing company should
      conduct anti-virus risk management covering in three aspects: increasing the
      awareness of occupational hazards, enhancing system ventilation, and improving
      personal health management measures.

PMID- 30241295
TI  - Concussion in University Level Sport: Knowledge and Awareness of Athletes and
      Coaches.
AB  - Using a cross-sectional survey concussion knowledge was evaluated among forty
      university-level athletes (n = 20, rugby union players; n = 20, Gaelic football
      players) and eight experienced team coaches (n = 2, rugby union; n = 2, Gaelic
      football; n = 1, soccer; n = 1, hockey; n = 1, netball; n = 1, basketball).
      Levels of knowledge of concussion were high across all participants. Coaches had
      higher knowledge scores for almost all areas; however, there was evidence of
      important gaps even in this group. Knowledge was not sufficient in identifying
      concussion, and when it is safe to return to play following a concussion.
      Impaired knowledge of how to recognise a concussion, and misunderstanding the
      need for rest and rehabilitation before return to play presents a hazard to
      health from second impact and more catastrophic brain injury. We discuss reasons
      for these guideline misconceptions, and suggest that attitude issues on the
      significance of concussion may underlie a willingness to want to play with a
      concussion. This suggests the current education on sport-related concussion needs
      to be expanded for the appropriate management of university-level contact sports.

PMID- 30241296
TI  - Comparison of Product Carbon Footprint Protocols: Case Study on Medium-Density
      Fiberboard in China.
AB  - Carbon footprint (CF) analysis is widely used to quantify the greenhouse gas
      (GHG) emissions of a product during its life cycle. A number of protocols, such
      as Publicly Available Specification (PAS) 2050, GHG Protocol Product Standard
      (GHG Protocol), and ISO 14067 Carbon Footprint of Products (ISO 14067), have been
      developed for CF calculations. This study aims to compare the criteria and
      implications of the three protocols. The medium-density fiberboard (MDF)
      (functional unit: 1 m3) has been selected as a case study to illustrate this
      comparison. Different criteria, such as the life cycle stage included, cut-off
      criteria, biogenic carbon treatment, and other requirements, were discussed. A
      cradle-to-gate life cycle assessment (LCA) for MDF was conducted. The CF values
      were -667.75, -658.42, and 816.92 kg of carbon dioxide equivalent (CO2e) with PAS
      2050, GHG protocol, and ISO 14067, respectively. The main reasons for the
      different results obtained were the application of different cut-off criteria,
      exclusion rules, and the treatment of carbon storage. A cradle-to-grave
      assessment (end-of-life scenarios: landfill and incineration) was also performed
      to identify opportunities for improving MDF production. A sensitivity analysis to
      assess the implications of different end-of-life disposals was conducted,
      indicating that landfill may be preferable from a GHG standpoint. The comparison
      of these three protocols provides insights for adopting appropriate methods to
      calculate GHG emissions for the MDF industry. A key finding is that for both LCA
      practitioners and policy-makers, PAS 2050 is preferentially recommended to assess
      the CF of MDF.

PMID- 30241298
TI  - Preliminary Study of Ultrasonic Welding as a Joining Process for Electrospun
      Nanofiber Mats.
AB  - Electrospinning can be used to create nanofiber mats for diverse applications,
      from wound dressings and tissue engineering to filters for medical and
      biotechnological applications. In most of these applications, it is necessary to
      fix the nanofiber mat on a macroscopic textile fabric, on another nanofiber mat
      or within a frame to keep it at the desired position. Due to their extremely low
      thickness and areal mass, however, nanofiber mats are easily destroyed by sewing,
      and in several situations glued bonds are too thick and not flexible enough. Here
      we report on ultrasonic welding of polyacrylonitrile nanofiber mats, suggesting
      this method as a joining process without destruction of the mat morphology for
      thermoplastic nanofiber mats. A variety of welding patterns results in different
      adhesion forces between both joined nanofiber mats and different failure
      mechanisms, with some welding patterns enabling bonding stronger than the mats
      themselves. Our findings show that ultrasonic welding is a possible joining
      method for polyacrylonitrile nanofiber mats.

PMID- 30241297
TI  - Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan
      Taipan (Oxyuranus scutellatus) Venom.
AB  - There is an unmet need for economical snakebite therapies with long shelf lives
      that are effective even with delays in treatment. The orally bioavailable, heat
      stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates
      antidotal characteristics for severe snakebite envenoming in both field and
      hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus
      scutellatus) demonstrates that LY333013, even with delayed oral administration,
      improves the chances of survival. Furthermore, LY333013 improves the performance
      of antivenom even after it no longer reverses neurotoxic signs. Our study is the
      first demonstration that neurotoxicity from presynaptic venom sPLA2S can be
      treated successfully, even after the window of therapeutic antivenom has closed.
      These results suggest that sPLA2 inhibitors have the potential to reduce death
      and disability and should be considered for the initial and adjunct treatment of
      snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to
      achieve these endpoints requires further investigation and development efforts.

PMID- 30241299
TI  - Two Novel Aspochalasins from the Gut Fungus Aspergillus sp. Z4.
AB  - Two novel aspochalasins, tricochalasin A (1) and aspochalasin A2 (2), along with
      three known compounds (3-5) have been isolated from the different culture broth
      of Aspergillus sp., which was found in the gut of a marine isopod Ligia oceanica.
      Compound 1 contains a rare 5/6/6 tricyclic ring fused with the aspochalasin
      skeleton. The structures were determined on the basis of electrospray ionisation
      mass spectroscopy (ESIMS), nuclear magnetic resonance (NMR) spectral data, and
      the absolute configurations were further confirmed by modified Mosher's method.
      Cytotoxicity against the prostate cancer PC3 cell line were assayed by the MTT
      method. Compound 3 showed strong activity while the remaining compounds showed
      weak activity.

PMID- 30241300
TI  - Virus-Like Particles Are a Superior Platform for Presenting M2e Epitopes to Prime
      Humoral and Cellular Immunity against Influenza Virus.
AB  - Influenza virus M2 protein has a highly conserved ectodomain (M2e) as a cross
      protective antigenic target. We investigated the antigenic and immunogenic
      properties of tandem repeat M2e (5xM2e) proteins and virus-like particles (5xM2e
      VLP) to better understand how VLP and protein platform vaccines induce innate and
      protective adaptive immune responses. Despite the high antigenic properties of
      5xM2e proteins, the 5xM2e VLP was superior to 5xM2e proteins in inducing IgG2a
      isotype antibodies, T cell responses, plasma cells and germinal center B cells as
      well as in conferring cross protection. Mice primed with 5xM2e VLP were found to
      be highly responsive to 5xM2e protein boost, overcoming the low immunogenicity
      and protective efficacy of 5xM2e proteins. Immunogenic differences between VLPs
      and proteins in priming immune responses might be due to an intrinsic ability of
      5xM2e VLP to stimulate dendritic cells secreting T helper type 1 (Th1) cytokines.
      We also found that 5xM2e VLP was effective in inducing inflammatory cytokines and
      chemokines, and in recruiting macrophages, monocytes, neutrophils, and CD11b+
      dendritic cells at the injection site. Therefore, this study provides evidence
      that 5xM2e VLP is an effective vaccine platform, inducing cross-protection by
      stimulating innate and adaptive immune responses.

PMID- 30241302
TI  - Effect of Chlorogenic Acids on Cognitive Function: A Randomized, Double-Blind,
      Placebo-Controlled Trial.
AB  - (1) Background: Chlorogenic acids (CGAs) have been attracting interest of late,
      owing to their health benefits. Here, we performed a randomized, double-blind,
      placebo-controlled trial to investigate whether CGAs improved cognitive function
      in humans. (2) Methods: Thirty-eight healthy participants were assigned to either
      the CGA group, which was given CGA-added beverage daily for 16 weeks, or the
      placebo group. Cognitive functions were assessed using the Japanese version of
      the CNS Vital Signs (Cognitrax). (3) Results: The CGA group showed significant
      increase in the Cognitrax domain scores for motor speed, psychomotor speed, and
      executive function compared with the placebo group, as well as an improvement in
      the shifting attention test scores. In blood analysis, the CGA group showed
      increased levels of apolipoprotein A1 and transthyretin, both of which are
      putative biomarkers for early-stage cognitive decline. (4) Conclusions: These
      results suggest that CGAs may improve some cognitive functions, which would help
      in the efficient performance of complex tasks.

PMID- 30241305
TI  - Practical Enantioselective Reduction of Ketones Using Oxazaborolidine Catalysts
      Generated In Situ from Chiral Lactam Alcohols.
AB  - Oxazaborolidine catalyst (CBS catalyst) has been extensively used for catalytic
      borane reduction with a predictable absolute stereochemistry and high
      enantioselectivity. However, the use of isolated CBS catalyst sometimes has the
      drawback of low reproducibility due to the aging of the CBS catalyst during
      storage. Therefore, we investigated a more reliable and practical method for the
      reduction of a variety of ketones including challenging substrates, primary
      aliphatic ketones, alpha,beta-enones, and trifluoromethyl ketones. This review
      surveys the developments in borane reduction using oxazaborolidine catalysts
      generated in situ from chiral lactam alcohols and borane.

PMID- 30241301
TI  - Mechanisms Underlying the Action and Synergism of Trastuzumab and Pertuzumab in
      Targeting HER2-Positive Breast Cancer.
AB  - Human epidermal growth factor receptor (HER) 2 (HER2) is overexpressed in 20-30%
      of breast cancers. HER2 is a preferred target for treating HER2-positive breast
      cancer. Trastuzumab and pertuzumab are two HER2-targeted monoclonal antibodies
      approved by the Food and Drug Administration (FDA) to use as adjuvant therapy in
      combination with docetaxel to treat metastatic HER2-positive breast cancer.
      Adding the monoclonal antibodies to treatment regimen has changed the paradigm
      for treatment of HER2-positive breast cancer. Despite improving outcomes, the
      percentage of the patients who benefit from the treatment is still low. Continued
      research and development of novel agents and strategies of drug combinations is
      needed. A thorough understanding of the molecular mechanisms underlying the
      action and synergism of trastuzumab and pertuzumab is essential for moving
      forward to achieve high efficacy in treating HER2-positive breast cancer. This
      review examined and analyzed findings and hypotheses regarding the action and
      synergism of trastuzumab and pertuzumab and proposed a model of synergism based
      on available information.

PMID- 30241304
TI  - Effect of Tourism Pressure on the Mediterranean Diet Pattern.
AB  - Despite proposed conceptual frameworks of eating behaviors, little is known about
      environmental factors contributing to changes in food habits. Few studies have
      reported the external influence of tourism on the inhabitants' eating patterns.
      The present study aimed to investigate whether tourism pressure affects Canary
      Islands inhabitants' adherence to the Mediterranean diet pattern. Data were
      obtained from a health and lifestyle population-based survey conducted in 2009
      and 2015. From the reported intake frequency, a Mediterranean diet score was
      defined (0 to 11 points). Tourist overnight stays, which were stratified by
      nationality and area of destination, were used as a proxy variable to measure
      tourism pressure. A multilevel linear regression analysis by restricted maximum
      likelihood estimation was performed to examine the relationship between tourism
      pressure and the Mediterranean diet score. A significant negative association
      between the Mediterranean diet score and British tourism pressure was observed
      (beta = -0.0064, p = 0.010), whereas German tourism pressure increased
      inhabitants' adherence (beta = 0.0092, p = 0.042). The socioeconomic level of
      tourists seems to play a role in differences in the tourism pressure effect by
      nationality. Further investigation of other highly touristic destinations is
      needed to confirm these findings that could contribute to a shift in tourism and
      public health nutrition policies.

PMID- 30241307
TI  - Assessment of General Public's Knowledge and Opinions towards Antibiotic Use and
      Bacterial Resistance: A Cross-Sectional Study in an Urban Setting, Rufisque,
      Senegal.
AB  - Background: Bacterial resistance is a major public health problem worldwide. One
      solution to this scourge is to sensitize the general public on rational use of
      antibiotics. Our goal was to assess people's knowledge and opinions about
      antibiotic use and bacterial resistance in an urban setting. Method: We performed
      a cross-sectional study. A convenience sampling was done. A questionnaire was
      administered to 400 persons during face-to-face interviews. Results: Most
      respondents thought that antibiotics are effective against colds/flu (69.8%),
      cough (72.3%) and sore throat (64.4%). At the same time, 42.8% stated that
      antibiotic therapy can be stopped as soon as the symptoms disappear. Only 8.8%
      and 41.8% of people knew that handwashing and vaccination prevented bacterial
      resistance. Globally, 7% of people had a good knowledge. Socio-demographic
      variables were not associated with the level of knowledge. The main sources of
      information were entourage and pharmacy staff. Regarding the opinions, 78.3% of
      surveyed participants the people thought that that people overuse antibiotics.
      Additionally, 28% said that they have no role to play against bacterial
      resistance. Conclusion: People living in an urban setting had a low knowledge
      about antibiotic use and bacterial resistance. There is a need to implement
      awareness campaigns. Further studies on population practices toward antibiotic
      use are necessary.

PMID- 30241303
TI  - Lab-on-Chip for Exosomes and Microvesicles Detection and Characterization.
AB  - Interest in extracellular vesicles and in particular microvesicles and exosomes,
      which are constitutively produced by cells, is on the rise for their huge
      potential as biomarkers in a high number of disorders and pathologies as they are
      considered as carriers of information among cells, as well as being responsible
      for the spreading of diseases. Current methods of analysis of microvesicles and
      exosomes do not fulfill the requirements for their in-depth investigation and the
      complete exploitation of their diagnostic and prognostic value. Lab-on-chip
      methods have the potential and capabilities to bridge this gap and the technology
      is mature enough to provide all the necessary steps for a completely automated
      analysis of extracellular vesicles in body fluids. In this paper we provide an
      overview of the biological role of extracellular vesicles, standard biochemical
      methods of analysis and their limits, and a survey of lab-on-chip methods that
      are able to meet the needs of a deeper exploitation of these biological entities
      to drive their use in common clinical practice.

PMID- 30241306
TI  - Solar Radiation Exposure and Outdoor Work: An Underestimated Occupational Risk.
AB  - A considerably high number of outdoor workers worldwide are constantly exposed
      for the majority of their working life to solar radiation (SR); this exposure is
      known to induce various adverse health effects, mainly related to its ultraviolet
      (UV) component. The skin and the eye are the principal target organs for both
      acute and long-term exposure. Actinic keratosis, non-melanoma skin cancers, and
      malignant melanoma are the main long-term adverse skin effects, whereas in the
      eye pterygium, cataracts, and according to an increasing body of evidence,
      macular degeneration may be induced. Despite this, SR exposure risk is currently
      undervalued, if not neglected, as an occupational risk factor for outdoor
      workers. SR exposure is influenced by various environmental and individual
      factors, and occupation is one of the most relevant. For a better understanding
      of this risk and for the development of more effective prevention strategies, one
      of the main problems is the lack of available and adequate methods to estimate SR
      worker exposure, especially long-term exposure. The main aims of this review were
      to provide a comprehensive overview of SR exposure risk of outdoor workers,
      including the UV exposure levels and the main methods recently proposed for short
      term and cumulative exposure, and to provide an update of knowledge on the main
      adverse eye and skin effects. Finally, we also outline here preventive
      interventions to reduce occupational risk.

PMID- 30241308
TI  - Methionine Sulfoxide Reductases of Archaea.
AB  - Methionine sulfoxide reductases are found in all domains of life and are
      important in reversing the oxidative damage of the free and protein forms of
      methionine, a sulfur containing amino acid particularly sensitive to reactive
      oxygen species (ROS). Archaea are microbes of a domain of life distinct from
      bacteria and eukaryotes. Archaea are well known for their ability to withstand
      harsh environmental conditions that range from habitats of high ROS, such as
      hypersaline lakes of intense ultraviolet (UV) radiation and desiccation, to
      hydrothermal vents of low concentrations of dissolved oxygen at high temperature.
      Recent evidence reveals the methionine sulfoxide reductases of archaea function
      not only in the reduction of methionine sulfoxide but also in the ubiquitin-like
      modification of protein targets during oxidative stress, an association that
      appears evolutionarily conserved in eukaryotes. Here is reviewed methionine
      sulfoxide reductases and their distribution and function in archaea.

PMID- 30241309
TI  - Trichosanthis Pericarpium Aqueous Extract Protects H9c2 Cardiomyocytes from
      Hypoxia/Reoxygenation Injury by Regulating PI3K/Akt/NO Pathway.
AB  - Trichosanthis Pericarpium (TP) is a traditional Chinese medicine for treating
      cardiovascular diseases. In this study, we investigated the effects of TP aqueous
      extract (TPAE) on hypoxia/reoxygenation (H/R) induced injury in H9c2
      cardiomyocytes and explored the underlying mechanisms. H9c2 cells were cultured
      under the hypoxia condition induced by sodium hydrosulfite for 30 min and
      reoxygenated for 4 h. Cell viability was measured by MTT assay. The amounts of
      LDH, NO, eNOS, and iNOS were tested by ELISA kits. Apoptotic rate was detected by
      Annexin V-FITC/PI staining. QRT-PCR was performed to analyze the relative mRNA
      expression of Akt, Bcl-2, Bax, eNOS, and iNOS. Western blotting was used to
      detect the expression of key members in the PI3K/Akt pathway. Results showed that
      the pretreatment of TPAE remarkably enhanced cell viability and decreased
      apoptosis induced by H/R. Moreover, TPAE decreased the release of LDH and
      expression of iNOS. In addition, TPAE increased NO production and Bcl-2/Bax
      ratio. Furthermore, the mRNA and protein expression of p-Akt and eNOS were
      activated by TPAE pretreatment. On the contrary, a specific inhibitor of PI3K,
      LY294002 not only inhibited TPAE-induced p-Akt/eNOS upregulation but alleviated
      its anti-apoptotic effects. In conclusion, results indicated that TPAE protected
      against H/R injury in cardiomyocytes, which consequently activated the
      PI3K/Akt/NO signaling pathway.

PMID- 30241311
TI  - Resource Allocation in Wireless Powered IoT System: A Mean Field Stackelberg Game
      Based Approach.
AB  - The IoT system has become a significant component of next generation networks,
      and drawn a lot of research interest in academia and industry. As the sensor
      nodes in the IoT system are always battery-limited devices, the power control
      problem is a serious problem in the IoT system which needs to be solved. In this
      paper, we research the resource allocation in the wireless powered IoT system,
      which includes one hybrid access point (HAP) and many wireless sensor nodes, to
      obtain the optimal power level for information transmission and energy transfer
      simultaneously. The relationship between the HAP and the sensor nodes are
      formulated as the Stackelberg game, and the dynamic variations of the energy for
      both the HAP and IoT devices are formulated through the dynamic game with mean
      field control. Then the power control in the wireless powered IoT system is
      formulated as a mean field Stackelberg game model. We aim to minimize the
      transmission cost for each sensor node based on optimally power resource
      allocation. Meanwhile, we attempt to minimize the energy transfer cost based on
      power control. As a result, the optimal solutions based on the mean field control
      of the sensor nodes and the HAP are achieved through dynamic programming theory
      and the law of large numbers, and epsilon -Nash equilibriums can be obtained. The
      energy variations for both the sensor nodes and HAP after the control of resource
      allocation based on the proposed approach are verified based on the simulation
      results.

PMID- 30241310
TI  - An 8-Week, Low Carbohydrate, High Fat, Ketogenic Diet Enhanced Exhaustive
      Exercise Capacity in Mice Part 2: Effect on Fatigue Recovery, Post-Exercise
      Biomarkers and Anti-Oxidation Capacity.
AB  - A low-carbohydrate, high-fat ketogenic diet (KD) is a nutritional approach
      ensuring that the body utilizes lipids. In our previous study, we found that an
      eight-week ketogenic high-fat, low-carbohydrate diet increased the capacity of
      endurance exercise in mice without aggravated muscle injury, despite the decrease
      of absolute muscle volume. The potential mechanism is most possibly to be
      enhanced capacity to mobilize and utilize fat. In the present study, we
      investigated whether a ketogenic diet influences post-exercise recovery by
      measuring blood biomarkers, muscle and liver oxidative state as well as fatigue
      recovery 24 h post exercise by employing an open-field locomotion test. Several
      biochemistry markers indicating exercise-induced injury after exhaustive exercise
      were improved by KD, followed by a 24-h rest with free feed access, including
      lactate. No aggravated hepatic oxidative damage was observed, whereas muscular
      oxidative stress was increased by KD. Accelerated recovery induced by exhaustive
      exercise was also observed from blood biomarkers of injury. For fatigue recovery,
      lactate concentration, a marker often employed as exhaustion index was lowered by
      KD, whereas an open field test showed that KD application contributed to
      increased locomotion after exhaustive exercise, followed by a 24-h rest. These
      results suggest that KD has the potential to be used as a fatigue-preventing
      and/or recovery-promoting diet approach in endurance athletes.

PMID- 30241312
TI  - Controlled Construction of Stable Network Structure Composed of Honeycomb-Shaped
      Microhydrogels.
AB  - Recently, the construction of models for multicellular systems such as tissues
      has been attracting great interest. These model systems are expected to reproduce
      a cell communication network and provide insight into complicated functions in
      living systems./Such network structures have mainly been modelled using a droplet
      and a vesicle. However, in the droplet and vesicle network, there are
      difficulties attributed to structural instabilities due to external stimuli and
      perturbations. Thus, the fabrication of a network composed of a stable component
      such as hydrogel is desired. In this article, the construction of a stable
      network composed of honeycomb-shaped microhydrogels is described. We produced the
      microhydrogel network using a centrifugal microfluidic technique and a
      photosensitive polymer. In the network, densely packed honeycomb-shaped
      microhydrogels were observed. Additionally, we successfully controlled the degree
      of packing of microhydrogels in the network by changing the centrifugal force. We
      believe that our stable network will contribute to the study of cell
      communication in multicellular systems.

PMID- 30241314
TI  - Structure Prediction of Rare Earth Doped BaO and MgO Containing Aluminosilicate
      Glasses-the Model Case of Gd2O3.
AB  - The medium-range atomic structure of magnesium and barium aluminosilicate glasses
      doped with Gd2O3 as a model rare earth oxide is elucidated using molecular
      dynamics simulations. Our structure models rationalize the strong dependence of
      the luminescence properties of the glasses on their chemical composition. The
      simulation procedure used samples' atomic configurations, the so-called inherent
      structures, characterizing configurations of the liquid state slightly above the
      glass transition temperature. This yields medium-range atomic structures of
      network former and modifier ions in good agreement with structure predictions
      using standard simulated annealing procedures. However, the generation of a large
      set of inherent structures allows a statistical sampling of the medium-range
      order of Gd3+ ions with less computational effort compared to the simulated
      annealing approach. It is found that the number of Si-bound non-bridging oxygen
      in the vicinity of Gd3+ considerably increases with growing ionic radius and
      concentration of network-modifier ions. In addition, structure predictions
      indicate a low driving force for clustering of Gd3+, yet no precise correlation
      between the atomic structure and luminescence lifetimes can be conclusively
      established. However, the structure models provided in this study can serve as a
      starting point for future quantum mechanical simulations to shed a light on the
      relation between the atomic structure and optical properties of rare earth doped
      aluminosilicate glasses.

PMID- 30241313
TI  - Improved Socio-Emotional and Behavioral Functioning in Students with Autism
      Following School-Based Smartglasses Intervention: Multi-Stage Feasibility and
      Controlled Efficacy Study.
AB  - Background: Students with Autism Spectrum Disorder (ASD) commonly demonstrate
      prominent social communication deficits, symptoms of attention
      deficit/hyperactivity disorder, and chronic irritability. These challenges hinder
      academic progress and frequently persist despite educational, behavioral, and
      medical interventions. An assistive smartglasses technology may aid these
      individuals, especially if the technology is efficacious in ecologically-valid
      school settings. This study explored the feasibility and efficacy of Empowered
      Brain, a computerized smartglasses intervention designed as a socio-emotional
      behavioral aid for students with ASD. Methods: This two-part six-week study
      involved four school children with ASD from a public elementary school. The study
      incorporated an initial three-week feasibility stage followed by a three-week
      controlled longitudinal efficacy stage. Both stages involved the use of a twice
      daily socio-emotional intervention with the smartglasses. Educators completed pre
      intervention and post-intervention Aberrant Behavioral Checklist (ABC) ratings at
      the start of the feasibility stage, and weekly during the efficacy stage. Primary
      outcome measures were improvements in the ABC subscales of irritability,
      hyperactivity, and social withdrawal. Results: Students in both feasibility and
      efficacy stages demonstrated improvements (decreases) in irritability,
      hyperactivity, and social withdrawal compared to a baseline period and control
      periods, respectively. Participants in the controlled efficacy stage demonstrated
      decreased ABC subscale scores of 90% for irritability, 41.6% for hyperactivity,
      and 45.6% for social withdrawal. An intervention exposure-response improvement in
      irritability and hyperactivity was found during the efficacy stage. Educators
      rated the technology as superior or vastly superior compared to other assistive
      technologies. Conclusion: A substantial number of school children with ASD
      demonstrate chronic and impairing cognitive and behavioral challenges. This study
      provides evidence that Empowered Brain, a smartglasses-based socio-emotional aid
      for autism, is both feasible and efficacious in improving symptoms of social
      withdrawal, irritability, and hyperactivity in students with autism. The
      improvement is demonstrated as part of a longitudinal school-based intervention.
      Further studies involving larger samples and incorporation of randomized
      controlled trial methodology are underway to further elucidate the impact of this
      technology.

PMID- 30241316
TI  - Influence of the Composition on the Environmental Impact of Soft Ferrites.
AB  - The aim of this paper is to analyze the influence of the composition on the
      environmental impact of the two main types of soft ferrites, allowing scientists
      and engineers to compare them based not only on cost and properties, but also on
      an environmental point of view. Iron oxides are the basis of soft ferrites, but
      these ferrites have a wide range of compositions, using materials such as
      manganese or nickel, which affect their magnetic properties, but also modify the
      environmental impact. A Life Cycle Assessment has been carried out for manganese
      zinc (MnZn) and nickel-zinc (NiZn) soft ferrites, with a Monte Carlo approach to
      assess multiple compositions. The LCA model was developed with SimaPro 8.4, using
      the EcoInvent v3.4 life cycle inventory database. Environmental impact values
      were calculated under the ReCiPe and Carbon Footprint methodologies, obtaining a
      broad variety of results depending on the composition. The results were also
      significantly different from the standard EcoInvent ferrite. For the analyzed
      soft ferrites, the presence of manganese or nickel is a key factor from an
      environmental perspective, as these materials involve high environmental impacts,
      and their supply risk has increased during recent years, making them a concern
      for European manufacturers.

PMID- 30241317
TI  - An Ab Initio QM/MM Study of the Electrostatic Contribution to Catalysis in the
      Active Site of Ketosteroid Isomerase.
AB  - The electric field in the hydrogen-bond network of the active site of ketosteroid
      isomerase (KSI) has been experimentally measured using vibrational Stark effect
      (VSE) spectroscopy, and utilized to study the electrostatic contribution to
      catalysis. A large gap was found in the electric field between the computational
      simulation based on the Amber force field and the experimental measurement. In
      this work, quantum mechanical (QM) calculations of the electric field were
      performed using an ab initio QM/MM molecular dynamics (MD) simulation and
      electrostatically embedded generalized molecular fractionation with conjugate
      caps (EE-GMFCC) method. Our results demonstrate that the QM-derived electric
      field based on the snapshots from QM/MM MD simulation could give quantitative
      agreement with the experiment. The accurate calculation of the electric field
      inside the protein requires both the rigorous sampling of configurations, and a
      QM description of the electrostatic field. Based on the direct QM calculation of
      the electric field, we theoretically confirmed that there is a linear correlation
      relationship between the activation free energy and the electric field in the
      active site of wild-type KSI and its mutants (namely, D103N, Y16S, and D103L).
      Our study presents a computational protocol for the accurate simulation of the
      electric field in the active site of the protein, and provides a theoretical
      foundation that supports the link between electric fields and enzyme catalysis.

PMID- 30241315
TI  - The Many Faces of Rap1 GTPase.
AB  - This review addresses the issue of the numerous roles played by Rap1 GTPase
      (guanosine triphosphatase) in different cell types, in terms of both physiology
      and pathology. It is one among a myriad of small G proteins with endogenous GTP
      hydrolyzing activity that is considerably stimulated by posttranslational
      modifications (geranylgeranylation) or guanine nucleotide exchange factors
      (GEFs), and inhibited by GTPase-activating proteins (GAPs). Rap1 is a ubiquitous
      protein that plays an essential role in the control of metabolic processes, such
      as signal transduction from plasma membrane receptors, cytoskeleton
      rearrangements necessary for cell division, intracellular and substratum
      adhesion, as well as cell motility, which is needed for extravasation or fusion.
      We present several examples of how Rap1 affects cells and organs, pointing to
      possible molecular manipulations that could have application in the therapy of
      several diseases.

PMID- 30241318
TI  - Vitamin D Supplementation and Nordic Walking Training Decreases Serum
      Homocysteine and Ferritin in Elderly Women.
AB  - The aim of the study was to verify if coupling 12 weeks of vitamin D
      supplementation and Nordic walking training favoured lowering the homocysteine
      (Hcy) level. Ninety-four elderly women were divided into three groups: Nordic
      walking (NW), supplemented (SG) and control (CG). The NW and SG groups received a
      weekly dose of 28,000 IU of vitamin D3. A blood analysis was performed at
      baseline, 1h after the first training session and at the end of the experiment.
      The amino acid profile (methionine and cysteine) and homocysteine concentration
      were determined. Additionally, the concentration of myokine was assessed. The
      first session of NW training reduced serum homocysteine, particularly among women
      with baseline homocysteine above 10 umol.L-1: 12.37 +/- 2.75 vs. 10.95 +/- 3.94
      umol.L-1 (p = 0.05). These changes were accompanied by shifts in the cysteine (p
      = 0.09) and methionine (p = 0.01) concentration, regardless of the Hcy
      concentration. Twelve weeks of training significantly decreased the homocysteine
      (9.91 +/- 2.78, vs. 8.90 +/- 3.14 umol.L-1, p = 0.05) and ferritin (94.23 +/-
      62.49 vs. 73.15 +/- 47.04 ng.mL-1, p = 0.05) concentrations in whole NW group.
      Also, in the NW group, ferritin correlated with the glucose level (r = 0.51, p =
      0.00). No changes in the myokine levels were observed after the intervention.
      Only the brain-derived neurotrophic factor dropped in the NW (42.74 +/- 19.92 vs.
      31.93 +/- 15.91 ng.mL-1, p = 0.01) and SG (37.75 +/- 8.08 vs. 16.94 +/- 12.78
      ng.mL-1, p = 0.00) groups. This study presents a parallel decrease of
      homocysteine and ferritin in response to regular training supported by vitamin D
      supplementation.

PMID- 30241319
TI  - Global Signaling Profiling in a Human Model of Tumorigenic Progression Indicates
      a Role for Alternative RNA Splicing in Cellular Reprogramming.
AB  - Intracellular signaling is controlled to a large extent by the phosphorylation
      status of proteins. To determine how human breast cells can be reprogrammed
      during tumorigenic progression, we profiled cell lines in the MCF10A lineage by
      phosphoproteomic analyses. A large cluster of proteins involved in RNA splicing
      were hypophosphorylated as cells progressed to a hyperplastic state, and then
      hyperphosphorylated after progression to a fully metastatic phenotype. A
      comprehensive transcriptomic approach was used to determine whether alterations
      in splicing factor phosphorylation status would be reflected in changes in mRNA
      splicing. Results indicated that the degree of mRNA splicing trended with the
      degree of tumorigenicity of the 4 cell lines tested. That is, highly metastatic
      cell cultures had the greatest number of genes with splice variants, and these
      genes had greater fluctuations in expression intensities. Genes with high
      splicing indices were mapped against gene ontology terms to determine whether
      they have known roles in cancer. This group showed highly significant
      associations for angiogenesis, cytokine-mediated signaling, cell migration,
      programmed cell death and epithelial cell differentiation. In summary, data from
      global profiling of a human model of breast cancer development suggest that
      therapeutics should be developed which target signaling pathways that regulate
      RNA splicing.

PMID- 30241320
TI  - Interventions to Improve Vaccination Uptake and Cost Effectiveness of Vaccination
      Strategies in Newly Arrived Migrants in the EU/EEA: A Systematic Review.
AB  - Newly arrived migrants to the EU/EEA (arrival within the past five years), as
      well as other migrant groups in the region, might be under-immunised and lack
      documentation of previous vaccinations, putting them at increased risk of vaccine
      preventable diseases circulating in Europe. We therefore performed a systematic
      review conforming to PRISMA guidelines (PROSPERO CRD42016045798) to explore: (i)
      interventions that improve vaccine uptake among migrants; and (ii) cost
      effectiveness of vaccination strategies among this population. We searched
      MEDLINE, Embase, CINAHL, and Cochrane Database of Systematic Reviews (CDSR)
      between 1 January 2006 to 18 June 2018. We included three primary intervention
      studies performed in the EU/EEA or high-income countries and one cost
      effectiveness study relevant to vaccinations in migrants. Intervention studies
      showed small but promising impact only on vaccine uptake with social
      mobilization/community outreach, planned vaccination programs and education
      campaigns. Targeting migrants for catch-up vaccination is cost effective for
      presumptive vaccination for diphtheria, tetanus, and polio, and there was no
      evidence of benefit of carrying out pre-vaccination serological testing. The cost
      effectiveness is sensitive to the seroprevalence and adherence to vaccinations of
      the migrant. We conclude that scarce but direct EU/EEA data suggest social
      mobilization, vaccine programs, and education campaigns are promising strategies
      for migrants, but more research is needed. Research should also study cost
      effectiveness of strategies. Vaccination of migrants should continue to be a
      public heath priority in EU/EEA.

PMID- 30241321
TI  - Chemical Reporters and Their Bioorthogonal Reactions for Labeling Protein O
      GlcNAcylation.
AB  - Protein O-GlcNAcylation is a non-canonical glycosylation of nuclear,
      mitochondrial, and cytoplasmic proteins with the attachment of a single O-linked
      beta-N-acetyl-glucosamine (O-GlcNAc) moiety. Advances in labeling and identifying
      O-GlcNAcylated proteins have helped improve the understanding of O-GlcNAcylation
      at levels that range from basic molecular biology to cell signaling and gene
      regulation to physiology and disease. This review describes these advances in
      chemistry involving chemical reporters and their bioorthogonal reactions utilized
      for detection and construction of O-GlcNAc proteomes in a molecular mechanistic
      view. This detailed view will help better understand the principles of the
      chemistries utilized for biology discovery and promote continued efforts in
      developing new molecular tools and new strategies to further explore protein O
      GlcNAcylation.

PMID- 30241322
TI  - Planar Inverted-F Antenna (PIFA) Using Microfluidic Impedance Tuner.
AB  - This paper proposes a microfluidic impedance tuner that is applied to a planar
      inverted-F antenna (PIFA). The proposed microfluidic impedance tuner is designed
      while using a simple double-stub and the impedance is changed by tuning the stub
      length. In this work, the stub length can be tuned by injecting a liquid metal
      alloy to the microfluidic channels. Initially, the PIFA operates at 900 MHz with
      impedance matching of 50 Omega. The impedance is mismatched when a hand is placed
      close to the antenna. The mismatched impedance is matched to 50 Omega by
      injecting the liquid metal alloy. The antenna is fabricated on the FR-4
      substrate, and the impedance tuner is fabricated on polydimethylsiloxane (PDMS).
      In order to inject the liquid metal alloy, a piezoelectric micropump and
      microprocessor are used in the measurement. At 900 MHz, the return loss is
      successfully tuned from 4.69 dB to 18.4 dB when a hand is placed 1 mm above the
      antenna.

PMID- 30241323
TI  - Expression of Insulin-Like Growth Factor Binding Protein-5 (IGFBP5) Reverses
      Cisplatin-Resistance in Esophageal Carcinoma.
AB  - Cisplatin (CDDP) is one of the front-line chemotherapeutic drugs used in the
      treatment of esophageal squamous cell carcinoma (ESCC). Occurrence of resistance
      to CDDP has become one of the main challenges in cancer therapy. In this study,
      the gene expression profile of CDDP-resistant ESCC cells was investigated and
      molecular approaches were explored in an attempt to reverse the CDDP resistance.
      A CDDP-resistant SLMT-1/CDDP1R cell line was established from SLMT-1 cells by
      subculturing in the medium containing an increasing concentration of CDDP (0.1
      1MUg/mL). Mitochondrial (MTS) cytotoxicity assay, cell proliferation assay and
      cell morphology were used to assess the acquisition of cisplatin-resistance. The
      most differentially expressed gene in SLMT-1/CDDP1R cells was identified by cDNA
      microarray analysis compared with the parental SLMT-1 cells and validated by
      quantitative real-time polymerase chain reaction (qPCR). Association between
      expression of the most differentially expressed target gene to cisplatin
      resistance was verified by RNA interference. An attempt to reversecisplatin
      resistance phenotypes was made by using the vector expressing the most
      downregulated target gene in the CDDP-resistant cells. A CDDP-resistant ESCC cell
      line, SLMT-1/CDDP1R, was established with 2.8-fold increase CDDP-resistance
      (MTS50 = 25.8 MUg/mL) compared with the parental SLMT-1 cells. cDNA microarray
      analysis revealed that IGFBP5 showed the highest level of downregulation in SLMT
      1/CDDP1R cells compared with the parental SLMT-1 cells. Suppression of IGFBP5
      mediated by IGFBP5-targeting siRNA in parental SLMT-1 cells confirmed that IGFBP5
      suppression in ESCC cells would induce CDDP-resistance. More importantly,
      upregulation of IGFBP5 using IGFBP5 expression vector reduced cisplatin
      resistance in SLMT-1/CDDP1R cells by 41%. Thus, our results demonstrated that
      IGFBP5 suppression is one of the mechanisms for the acquisition of cisplatin
      resistance in ESCC cells. Cisplatin-resistance phenotype can be reversed by
      increasing the expression level of IGFBP5. The overall findings of this study
      thus offered a new direction for reversing the CDDP resistance in ESCC and
      possibly in other cancer types with further investigations in future.

PMID- 30241324
TI  - Effects of a 36-h Survival Training with Sleep Deprivation on Oxidative Stress
      and Muscle Damage Biomarkers in Young Healthy Men.
AB  - The aim of this study was to analyze changes in oxidative stress and muscle
      damage markers during a 36-h survival training combined with sleep deprivation.
      The study included 23 male students of physical education (specialty: Physical
      Education for Uniformed Services), randomly divided into the survival or control
      group. The students in the survival group completed a 36-h survival training with
      moderate to low physical activity, without the possibility to sleep. The students
      in the control group performed only physical activity included in daily routines
      and had a normal sleep pattern. No significant changes in measured parameters
      were seen in the control group throughout the study period. In the survival
      group, plasma lipid hydroperoxides (LHs) and creatine kinase (CK) activity
      increased at 24 h and remained elevated up to 36 h (main effects for LHs: time, p
      = 0.006 and group * time, p = 0.00008; main effects for CK: time, p = 0.000001,
      group, p = 0.005, and group * time, p = 0.000001). A 12-h recovery was sufficient
      to normalize both LHs and CK to the pre-training level; in fact, the post
      recovery LHs and CK levels were even lower than at baseline. Residual total
      antioxidant capacity (TAC) of plasma (without the major constituents: uric acid
      and albumin) was elevated at both 24 h and 36 h of survival training, but not
      following a 12-h recovery (main effects: group, p = 0.001 and group * time, p =
      0.04). In turn, the activity of glutathione peroxidase (GPx) in whole blood and
      superoxide dismutase (SOD) in erythrocytes decreased between 24 h and 36 h of
      survival training (main group effect for GPx, p = 0.038 and SOD, p = 0.045). In
      conclusion, these findings imply that a 36-h survival training with sleep
      deprivation impairs enzymatic antioxidant defense, increases lipid peroxidation,
      and induces muscle damage. Our findings also indicate that at least in the case
      of young physically active men, a 12-h recovery after the 36-h period of physical
      activity with sleep deprivation may be sufficient for the normalization of
      oxidative and muscle damage markers and restoration of blood prooxidant
      antioxidant homeostasis.

PMID- 30241325
TI  - Commencing Nutrient Supplements before Full Enteral Feed Volume Achievement Is
      Beneficial for Moderately Preterm to Late Preterm Low Birth Weight Babies: A
      Prospective, Observational Study.
AB  - The aim of this study was to observe after following a routine change in the
      feeding protocol whether the earlier introduction of nutrient supplements
      improved nutritional outcomes in moderately preterm to late preterm low birth
      weight (LBW) babies. In this prospective observational study, LBW babies between
      31 and 39 weeks' gestation admitted to a Special Care Nursery were assigned to
      two groups (F80, n = 45, F160, n = 42) upon commencing nutrient supplement at
      total fluid intake achievement of 80 or 160 mL/kg/day. Outcomes included weight,
      protein intake, biochemical markers, feeding intolerance, and length of stay
      (LOS). F80 nutrient supplements commenced before F160 (2.8 vs. 6.7 days, p <
      0.0001) and lasted longer (15.2 vs. 12.2 days, p < 0.03). Weight gain velocity
      and LOS were similar. F80 mean protein intake during the first 10 days was higher
      (3.38 vs. 2.74 g/kg/day, p < 0.0001). There were fewer infants with protein
      intake <3 g/kg/day in the F80 group (8% vs. 65%, p < 0001). F80 babies regained
      birthweight almost two days earlier (7.5 vs. 9.4 days, p < 0.01). Weight gain Z
      scores revealed an attenuation of the trend towards lower weight percentiles in
      the F80 group. Feeding intolerance was decreased for F80 (24.4% vs. 47.6%, p <
      0.03). There were no adverse outcomes. Earlier nutrient supplementation for LBW
      babies lifts mean protein intake to above 3 g/kg/day and reduces both the
      duration of post-birth weight loss and incidence of feeding intolerance.

PMID- 30241327
TI  - Analysis of Nutritional Supplements Consumption by Squash Players.
AB  - The aim of the present study is to analyse nutritional supplements (NS)
      consumption by squash players of different levels (international vs. national). A
      total of 14 international players and 28 national ones answered a NS consumption
      frequency questionnaire that had been previously validated. A T-Student test was
      used for independent samples and a chi2 test was used in the comparative analysis
      among athletes of different levels. International level players consume NS in
      greater proportion vs. national level players (100% vs. 67.9% p = 0.017), with
      differences in the consumption of bicarbonate of soda, glutamine, branched-chain
      amino acids, and flaxseed oil (p < 0.05). Even though international level
      athletes show a greater total number of NS, as well as of the total of NS of each
      of the categories based on scientific evidence level (sports food, medical
      supplements, and ergogenic aids of groups A, B, C, and D) in relation to the
      national level athletes, no statistically significant differences were detected
      (p > 0.05). With regard to nutritional advice, there are also differences among
      performance levels (p = 0.003), being personal trainers (28.6%) and dietitians
      nutritionists (21.4%) the greatest prescribers when it comes to international
      level players, whereas 55.6% of the national-level players do not receive
      nutritional advice. The pattern of NS consumption, based on evidence level, is
      unbalanced and its performance could be favored if the dietitian-nutritionist
      were included as a nutritional advisor for these athletes.

PMID- 30241326
TI  - Lipid Emulsion Inhibits the Late Apoptosis/Cardiotoxicity Induced by Doxorubicin
      in Rat Cardiomyoblasts.
AB  - This study aimed to examine the effect of lipid emulsion on the cardiotoxicity
      induced by doxorubicin in H9c2 rat cardiomyoblasts and elucidates the associated
      cellular mechanism. The effects of lipid emulsion on cell viability, Bax, cleaved
      caspase-8, cleaved capase-3, Bcl-XL, apoptosis, reactive oxygen species (ROS),
      malondialdehyde, superoxide dismutase (SOD), catalase and mitochondrial membrane
      potential induced by doxorubicin were examined. Treatment with doxorubicin
      decreased cell viability, whereas pretreatment with lipid emulsion reduced the
      effect of doxorubicin by increasing cell viability. Lipid emulsion also
      suppressed the increased expression of cleaved caspase-3, cleaved caspase-8, and
      Bax induced by doxorubicin. Moreover, pretreatment with lipid emulsion decreased
      the increased Bax/Bcl-XL ratio induced by doxorubicin. Doxorubicin-induced late
      apoptosis was reduced by treatment with lipid emulsion. In addition, pretreatment
      with lipid emulsion prior to doxorubicin enhanced glycogen synthase kinase-3beta
      phosphorylation. The increased malondialdehyde and ROS levels by doxorubicin were
      reduced by lipid emulsion pretreatment. Furthermore, lipid emulsion attenuated
      the reduced SOD and catalase activity and the decreased mitochondrial membrane
      potential induced by doxorubicin. Taken together, these results suggest that
      lipid emulsion attenuates doxorubicin-induced late apoptosis, which appears to be
      associated with the inhibition of oxidative stress induced by doxorubicin.

PMID- 30241329
TI  - Self-Adaption Matched Filter and Bi-Directional Difference Method for Moving
      Target Detection.
AB  - In this paper, a self-adaption matched filter (SMF) and bi-directional difference
      techniques are proposed to detect a small moving target in urban environments.
      Firstly, the SMF technique is proposed to improve the signal-to-interference
      noise ratio (SINR) by using the power factor. The properties of the transmitting
      signal, the target echoes and the interference and noise are considered during
      the power factor generation. The amplitude coherent accumulation technique that
      extracts the coherent amplitude information of echoes after being processed by
      the SMF, is used to improve the SINR based on multiple measurements. Finally, the
      bi-directional difference technique is proposed to distinguish the target echoes
      and the interference/noise. Simulations and experiments are conducted to validate
      and demonstrate that small moving targets can be detected with high probability
      using the proposed method in urban environments, even with just one measurement.

PMID- 30241328
TI  - Glycaemic Index of Maternal Dietary Carbohydrate Differentially Alters Fto and
      Lep Expression in Offspring in C57BL/6 Mice.
AB  - Maternal diet and gestational hyperglycaemia have implications for offspring
      health. Leptin (LEP) and fat mass and obesity-associated (FTO) alleles are known
      to influence body fat mass in humans, potentially via effects on appetite. We
      hypothesized that expression of Fto, Lep, and other appetite-related genes (Argp,
      Npy, Pomc, Cart, Lepr) in the offspring of female mice are influenced by the
      glycaemic index (GI) of carbohydrates in the maternal diet. C57BL/6 mice were
      randomly assigned to low or high GI diets and mated with chow-fed males at eight
      weeks of age. Male pups were weaned at four weeks and randomly divided into two
      groups, one group following their mother's diet (LL and HH), and one following
      the standard chow diet (LC and HC) to 20 weeks. Fto expression was 3.8-fold
      higher in the placenta of mothers fed the high GI diet (p = 0.0001) and 2.5-fold
      higher in the hypothalamus of 20-week old offspring fed the high GI (HH vs. LL, p
      < 0.0001). By contrast, leptin gene (Lep) expression in visceral adipose tissue
      was 4.4-fold higher in four-week old offspring of low GI mothers (LC vs. HC, p <
      0.0001) and 3.3-fold higher in visceral adipose tissue of 20-week old animals (LL
      vs. HH, p < 0.0001). Plasma ghrelin and leptin levels, and hypothalamic appetite
      genes were also differentially regulated by maternal and offspring diet. These
      findings provide the first evidence in an animal model that maternal high GI
      dietary carbohydrates that are digested and absorbed faster may contribute to
      programming of appetite in offspring.

PMID- 30241330
TI  - Research Progress of NiMn Layered Double Hydroxides for Supercapacitors: A
      Review.
AB  - The research on supercapacitors has been attractive due to their large power
      density, fast charge/discharge speed and long lifespan. The electrode materials
      for supercapacitors are thus intensively investigated to improve the
      electrochemical performances. Various transition metal layered double hydroxides
      (LDHs) with a hydrotalcite-like structure have been developed to be promising
      electrode materials. Earth-abundant metal hydroxides are very suitable electrode
      materials due to the low cost and high specific capacity. This is a review paper
      on NiMn LDHs for supercapacitor application. We focus particularly on the recent
      published papers using NiMn LDHs as electrode materials for supercapacitors. The
      preparation methods for NiMn LDHs are introduced first. Then, the structural
      design and chemical modification of NiMn LDH materials, as well as the composites
      and films derived from NiMn LDHs are discussed. These approaches are proven to be
      effective to enhance the performance of supercapacitor. Finally, the reports
      related to NiMn LDH-based asymmetric supercapacitors are summarized. A brief
      discussion of the future development of NiMn LDHs is also provided.

PMID- 30241331
TI  - Family Patterns and Suicidal and Violent Behavior among Adolescent Girls-Genogram
      Analysis.
AB  - An increase in extreme self-destructive and aggressive behaviors in adolescents
      has been observed in recent years. Therapeutic effectiveness seems to depend on
      an adequate recognition of factors that might increase the risk of extreme
      destructive behaviors. The aim of this study was to identify the family patterns
      that should draw therapeutic attention due to their importance for suicidal or
      violent behaviors in adolescent girls. The study involved 140 participants, aged
      13-17, including 40 girls after suicide attempts, 40 girls using violence, and 60
      girls without destructive behavior at all. The Genograms were used to assess the
      family structure, relationships between family members, and family projections.
      The data was analyzed by polynomial logistic regression, analysis of variance,
      and discriminant analysis. Emotional distance and hidden projections (related to
      diseases) were the most significant predictors of suicidal behaviors in the
      studied adolescent girls. Alcohol abuse by significant family members, especially
      by male family members, and a lesser role of hidden projections, were the most
      significant predictors of violent behaviors. Interventions designed to reduce
      risk of destructive behaviors among adolescents need to take account of the
      specific family patterns.

PMID- 30241332
TI  - Isolation and Chemical Characterization of Chondroitin Sulfate from Cartilage By
      Products of Blackmouth Catshark (Galeus melastomus).
AB  - Chondroitin sulfate (CS) is a glycosaminoglycan actively researched for
      pharmaceutical, nutraceutical and tissue engineering applications. CS extracted
      from marine animals displays different features from common terrestrial sources,
      resulting in distinct properties, such as anti-viral and anti-metastatic.
      Therefore, exploration of undescribed marine species holds potential to expand
      the possibilities of currently-known CS. Accordingly, we have studied for the
      first time the production and characterization of CS from blackmouth catshark
      (Galeus melastomus), a shark species commonly discarded as by-catch. The process
      of CS purification consists of cartilage hydrolysis with alcalase, followed by
      two different chemical treatments and ending with membrane purification. All
      steps were optimized by response surface methodology. According to this, the best
      conditions for cartilage proteolysis were established at 52.9  degrees C and pH =
      7.31. Subsequent purification by either alkaline treatment or hydroalcoholic
      alkaline precipitation yielded CS with purities of 81.2%, 82.3% and 97.4%
      respectively, after 30-kDa membrane separation. The molecular weight of CS
      obtained ranges 53-66 kDa, depending on the conditions. Sulfation profiles were
      similar for all materials, with dominant CS-C (GlcA-GalNAc6S) units (55%),
      followed by 23-24% of CS-A (GlcA-GalNAc4S), a substantial amount (15-16%) of CS-D
      (GlcA2S-GalNAc6S) and less than 7% of other disulfated and unsulfated
      disaccharides.

PMID- 30241333
TI  - Role of Mitochondrial Dysfunction in Degenerative Brain Diseases, an Overview.
AB  - Mitochondria are multifaceted organelles that serve to power critical neuronal
      functions.[...].

PMID- 30241334
TI  - Enhanced Photoelectrochemical Properties of Ti3+ Self-Doped Branched TiO2 Nanorod
      Arrays with Visible Light Absorption.
AB  - A novel Ti3+ self-doped branched rutile TiO2 nanorod arrays (NRAs) was
      successfully grown on an F-doped tin oxide (FTO) transparent conductive glass by
      a combined hydrothermal and magnetron sputtering method. Surface morphology,
      structure, optical properties, and photoelectrochemical behavior of the branched
      TiO2 NRAs are determined. Using TiO2 nanoparticles (NPs) deposited on the top of
      the nanorods as seeds, TiO2 nanobranches can easily grow on the top of the
      nanorods. Moreover, the Ti3+ defects in the TiO2 NPs and associated oxygen
      vacancies, and the nanobranches expend the optical absorption edge of the TiO2
      NRAs from 400 nm to 510 nm. Branched TiO2 NRAs exhibit excellent
      photoelectrochemical properties compared to the pure TiO2 NRAs, as revealed by
      photoelectrochemical measurements. This enhanced photoelectrochemical properties
      is induced by the increased surface area and expanded optical absorption range.
      Due to their favorable characteristics, these novel branched TiO2 NRAs will
      provide a new path to the fabrication of hierarchical nanostructured materials.

PMID- 30241336
TI  - Catestatin Regulates Epithelial Cell Dynamics to Improve Intestinal Inflammation.
AB  - Ulcerative colitis (UC) is characterized by aberrant regulation of tight
      junctions (TJ), signal transducer and activator of transcription 3 (STAT3), and
      interleukin (IL)-8/18, which lead to intestinal barrier defects. Catestatin
      (CST), an enterochromaffin-derived peptide, regulates immune communication and
      STAT-3 in the inflamed intestine. Here, we investigated the effects of CST during
      the development of inflammation using human biopsies from patients with active
      UC, human colonic epithelial cells (Caco2), and an experimental model of UC
      (dextran sulfate sodium [DSS]-colitis). In UC patients, the protein and mRNA
      level of CST was significantly decreased. Colonic expression of CST showed a
      strong positive linear relationship with TJ proteins and STAT3, and a strong
      negative correlation with IL-8 and IL-18. Intra-rectal administration of CST
      reduced the severity of experimental colitis, IL-18 colonic levels, maintained TJ
      proteins and enhanced the phosphorylation of STAT3. CST administration increased
      proliferation, viability, migration, TJ proteins, and p-STAT3 levels, and reduced
      IL-8 & IL-18 in LPS- & DSS-induced Caco2 cell epithelial injury, and the presence
      of STAT-3 inhibitor abolished the beneficial effect of CST. In inflammatory
      conditions, we conclude that CST could regulate intestinal mucosal dynamic via a
      potential STAT3-dependent pathway that needs to be further defined. Targeting CST
      in intestinal epithelial cells (IECs) should be a promising therapeutic approach
      such as when intestinal epithelial cell homeostasis is compromised in UC
      patients.

PMID- 30241337
TI  - The Effect of Body Mass Index on Acute Cardiometabolic Responses to Graded
      Exercise Testing in Children: A Narrative Review.
AB  - Although the beneficial role of exercise for health is widely recognized, it is
      not clear to what extent the acute physiological responses (e.g., heart rate (HR)
      and oxygen uptake (VO2)) to a graded exercise test are influenced by nutritional
      status (i.e., overweight vs. normal-weight). Therefore, the main objectives of
      the present narrative review were to examine the effect of nutritional status on
      acute HR, and VO2 responses of children to exercise testing. For this purpose, we
      examined existing literature using PubMed, ISI, Scopus, and Google Scholar search
      engines. Compared with their normal-body mass index (BMI) peers, a trend of
      higher HRrest, higher HR during submaximal exercise testing, and lower HRmax was
      observed among overweight and obese children (according to BMI). Independent from
      exercise mode (walking, running, cycling, or stepping), exercise testing was
      metabolically more demanding (i.e., higher VO2) for obese and overweight children
      than for their normal-weight peers. Considering these cardiometabolic differences
      according to BMI in children might help exercise specialists to evaluate the
      outcome of a graded exercise test (GXT) (e.g., VO2max, HRmax) and to prescribe
      optimal exercise intensity in the context of development of exercise programs for
      the management of body mass.

PMID- 30241335
TI  - Race, Intergenerational Social Mobility and Stressful Life Events.
AB  - Background. Socioeconomic status (SES) has smaller protective effects on the
      health of African Americans, and the differential association between social
      mobility and stress may explain the diminished returns of SES for African
      Americans. Aim. This study tested the race/ethnic differences in the association
      between upward and downward social mobility and stress in a nationally
      representative sample of African American and White American adults. Methods.
      This study included 3570 African Americans and 891 non-Hispanic White Americans
      from the National Survey of American Life (NSAL), 2003. Race/ethnicity, gender,
      age, upward and downward social mobility (independent variable, defined as
      difference between parent and respondent education), and stressful life events
      (SLE, dependent variable) were measured. Linear regression models were used for
      data analysis. Results. In the pooled sample that included both races, upward and
      downward social mobility were both associated with SLE, the net of all
      covariates. Significant interactions were found between race/ethnicity and social
      mobility, suggesting a stronger association between social mobility and stress
      for White Americans than for African Americans. According to race-stratified
      models, upward and downward social mobility were associated with higher SLE for
      White Americans but not African Americans. Conclusion. Although upwardly and
      downwardly mobile White Americans experience more stress than the socially stable
      White Americans, African Americans do not experience a change in SLE related to
      their intergenerational social mobility.

PMID- 30241338
TI  - Rotating and Neurochemical Activity of Rats Lesioned with Quinolinic Acid and
      Transplanted with Bone Marrow Mononuclear Cells.
AB  - Huntington's disease (HD) is an inherited, neurodegenerative disorder that
      results from the degeneration of striatal neurons, mainly GABAergic neurons. The
      study of neurochemical activity has provided reliable markers to explain motor
      disorders. To treat neurodegenerative diseases, stem cell transplants with bone
      marrow (BM) have been performed for several decades. In this work we determine
      the effect of mononuclear bone marrow cell (mBMC) transplantation on the
      rotational behavior and neurochemical activity in a model of Huntington's disease
      in rats. Four experimental groups were organized: Group I: Control animals (n =
      5); Group II: Lesion with quinolinic acid (QA) in the striatum (n = 5); Group
      III: Lesion with QA and transplant with mBMC (n = 5); Group IV: Lesion with QA
      and transplant with culture medium (Dulbecco's modified Eagle's medium (DMEM)
      injection) (n = 5). The rotational activity induced by D-amphetamine was
      evaluated and the concentration of the neurotransmitter amino acids (glutamate
      and GABA) was studied. The striatal cell transplantation decreases the rotations
      induced by D-amphetamine (p < 0.04, Wilcoxon matched pairs test) and improves the
      changes produced in the levels of neurotransmitters studied. This work suggests
      that the loss of GABAergic neurons in the brain of rats lesioned with AQ produces
      behavioral and neurochemical alterations that can be reversed with the use of
      bone marrow mononuclear cell transplants.

PMID- 30241340
TI  - Novel Methylselenoesters Induce Programed Cell Death via Entosis in Pancreatic
      Cancer Cells.
AB  - Redox active selenium (Se) compounds have gained substantial attention in the
      last decade as potential cancer therapeutic agents. Several Se compounds have
      shown high selectivity and sensitivity against malignant cells. The cytotoxic
      effects are exerted by their biologically active metabolites, with methylselenol
      (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we
      previously synthesized a series of methylselenoesters that were active (GI50 < 10
      uM at 72 h) against a panel of cancer cell lines. Herein, we refined the
      mechanism of action of the two lead compounds with the additional synthesis of
      new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the
      programmed cell death mechanism for Se-compounds was identified. Both
      methylseleninic acid and the novel CH3SeH precursors induced entosis by cell
      detachment through downregulation of cell division control protein 42 homolog
      (CDC42) and its downstream effector beta1-integrin (CD29). To our knowledge, this
      is the first time that Se compounds have been reported to induce this type of
      cell death and is of importance in the characterization of the anticancerogenic
      properties of these compounds.

PMID- 30241341
TI  - Palladium-Catalyzed Room Temperature Acylative Cross-Coupling of Activated Amides
      with Trialkylboranes.
AB  - A highly efficient acylative cross-coupling of trialkylboranes with activated
      amides has been effected at room temperature to give the corresponding alkyl
      ketones in good to excellent yields by using 1,3-bis(2,6
      diisopropyl)phenylimidazolylidene and 3-chloropyridine co-supported palladium
      chloride, the PEPPSI catalyst, in the presence of K2CO3 in methyl tert-butyl
      ether. The scope and limitations of the protocol were investigated, showing good
      tolerance of acyl, cyano, and ester functional groups in the amide counterpart
      while halo group competed via the classical Suzuki coupling. The trialkylboranes
      generated in situ by hydroboration of olefins with BH3 or 9-BBN performed
      similarly to those separately prepared, making this protocol more practical.

PMID- 30241342
TI  - Geochemistry and the Origin of Life: From Extraterrestrial Processes, Chemical
      Evolution on Earth, Fossilized Life's Records, to Natures of the Extant Life.
AB  - In 2001, the first author (S.N.) led the publication of a book entitled
      "Geochemistry and the origin of life" in collaboration with Dr. Andre Brack
      aiming to figure out geo- and astro-chemical processes essential for the
      emergence of life. Since then, a great number of research progress has been
      achieved in the relevant topics from our group and others, ranging from the
      extraterrestrial inputs of life's building blocks, the chemical evolution on
      Earth with the aid of mineral catalysts, to the fossilized records of ancient
      microorganisms. Here, in addition to summarizing these findings for the origin
      and early evolution of life, we propose a new hypothesis for the generation and
      co-evolution of photosynthesis with the redox and photochemical conditions on the
      Earth's surface. Besides these bottom-up approaches, we introduce an experimental
      study on the role of water molecules in the life's function, focusing on the
      transition from live, dormant, and dead states through dehydration/hydration.
      Further spectroscopic studies on the hydrogen bonding behaviors of water
      molecules in living cells will provide important clues to solve the complex
      nature of life.

PMID- 30241343
TI  - Study of Lignin-Modified Silica Gel Adsorption after Association with Six
      Different Organophenylmercuric Compounds in Chloroform.
AB  - In this study, the adsorption of lignin-modified silica gel after association
      with six different organophenylmercuric compounds in chloroform was investigated.
      Adsorption reached approximately 90% of the maximum value within 15 min. The
      adsorption capacity, Fourier transform infrared spectroscopy, and interaction
      simulation results indicated that the adsorption proportion resulted from the
      strong dipole-dipole interaction between the lignin and analyte molecules, and
      was considered to be size- and structure-dependent. However, the pi-pi
      complexation interaction arising from the acidic aromatic moiety of the analyte,
      which was significant in an apolar environment, was not the major force
      responsible for the resulting adsorption. Additives, such as acid or ether, which
      competed with the analyte for the binding site on the lignin molecule, were not
      beneficial to the interaction, and thus not beneficial to the adsorption
      processes.

PMID- 30241339
TI  - Pleiotropic Effects of Metformin on Cancer.
AB  - Metformin (MTF) is a natural compound derived from the legume Galega officinalis.
      It is the first line antidiabetic drug for type 2 diabetes (T2D) treatment. One
      of its main antidiabetic effects results from the reduction of hepatic glucose
      release. First scientific evidence for the anticancer effects of MTF was found in
      animal research, published in 2001, and some years later a retrospective
      observational study provided evidence that linked MTF to reduced cancer risk in
      T2D patients. Its pleiotropic anticancer effects were studied in numerous in
      vitro and in vivo studies at the molecular and cellular level. Although the
      majority of these studies demonstrated that MTF is associated with certain
      anticancer properties, clinical studies and trials provided a mixed view on its
      beneficial anticancer effects. This review emphasizes the pleiotropic effects of
      MTF and recent progress made in MTF applications in basic, preclinical, and
      clinical cancer research.

PMID- 30241344
TI  - Neglected Functions of TFCP2/TFCP2L1/UBP1 Transcription Factors May Offer
      Valuable Insights into Their Mechanisms of Action.
AB  - In recent years, the TFCP2 (transcription factor cellular promoter 2)/TFCP2L1
      (TFCP2-like 1)/UBP1 (upstream binding protein 1) subfamily of transcription
      factors has been attracting increasing attention in the scientific community.
      These factors are very important in cancer, Alzheimer's disease, and other human
      conditions, and they can be attractive targets for drug development. However, the
      interpretation of experimental results is complicated, as in principle, any of
      these factors could substitute for the lack of another. Thus, studying their
      hitherto little known functions should enhance our understanding of mechanisms of
      their functioning, and analogous mechanisms might govern their functioning in
      medically relevant contexts. For example, there are numerous parallels between
      placental development and cancer growth; therefore, investigating the roles of
      TFCP2, TFCP2L1, and UBP1 in the placenta may help us better understand their
      functioning in cancer, as is evidenced by the studies of various other proteins
      and pathways. Our review article aims to call the attention of the scientific
      community to these neglected functions, and encourage further research in this
      field. Here, we present a systematic review of current knowledge of the
      TFCP2/TFCP2L1/UBP1 subfamily in reproduction, embryonic development, renal
      function, blood-pressure regulation, brain function, and other processes, where
      their involvement has not been studied much until now.

PMID- 30241346
TI  - Seco-Tetracenomycins from the Marine-Derived Actinomycete Saccharothrix sp. 10
      10.
AB  - Six new tetracenomycin congeners, saccharothrixones E-I (1-5) and 13-de-O
      methyltetracenomycin X (6), were isolated from the rare marine-derived
      actinomycete Saccharothrix sp. 10-10. Their structures were elucidated by
      spectroscopic analysis and time-dependent density functional theory (TDDFT)
      electronic circular dichroism (ECD) calculations. Saccharothrixones G (3) and H
      (4) are the first examples of tetracenomycins featuring a novel ring-A-cleaved
      chromophore. Saccharothrixone I (5) was determined to be a seco-tetracenomycin
      derivative with ring-B cleavage. The new structural characteristics, highlighted
      by different oxidations at C-5 and cleavages in rings A and B, enrich the
      structural diversity of tetracenomycins and provide evidence for tetracenomycin
      biosynthesis. Analysis of the structure-activity relationship of these compounds
      confirmed the importance of the planarity of the naphthacenequinone chromophore
      and the methylation of the polar carboxy groups for tetracenomycin cytotoxicity.

PMID- 30241345
TI  - The Interplay between Human Cytomegalovirus and Pathogen Recognition Receptor
      Signaling.
AB  - The cellular antiviral innate immune response is triggered upon recognition of
      specific viral components by a set of the host's cytoplasmic or membrane-bound
      receptors. This interaction induces specific signaling cascades that culminate
      with the production of interferons and the expression of interferon-stimulated
      genes and pro-inflammatory cytokines that act as antiviral factors, suppressing
      viral replication and restricting infection. Here, we review and discuss the
      different mechanisms by which each of these receptors is able to recognize and
      signal infection by the human cytomegalovirus (HCMV), an important human pathogen
      mainly associated with severe brain defects in newborns and disabilities in
      immunocompromised individuals. We further present and discuss the many
      sophisticated strategies developed by HCMV to evade these different signaling
      mechanisms and counteract the cellular antiviral response, in order to support
      cell viability and sustain its slow replication cycle.

PMID- 30241347
TI  - School Bag Weight as a Barrier to Active Transport to School among New Zealand
      Adolescents.
AB  - BACKGROUND: Excessive school bag weight is a barrier to active transport to
      school (ATS). This study examined parents' and adolescents' perceptions of school
      bag weights and actual school bag weights for adolescents in New Zealand.
      METHODS: Parents (n = 331; 76.7% women) completed a survey. Adolescents (n = 682;
      age 15.1 +/- 1.4 years; 57.3% boys) completed a survey, underwent anthropometry,
      and had their school bags weighed. RESULTS: Overall, 68.3% of parents perceived
      that adolescents' school bags were too heavy to carry to school. This parental
      perception differed by adolescents' mode of transport to school
      (active/motorized/combined: 35.1%/78.4%/68.8%, p < 0.001). Adolescents perceived
      that their school bags were too heavy to carry to walk (57.8%) or cycle (65.8%)
      to school. Adolescent perceptions differed by mode of transport to school (for
      walking (active/motorized/combined): 30.9%/69.2%/55.9% agree, p < 0.001; for
      cycling: 47.9%/72.8%/67.7%; p < 0.001). Actual school bag weight was, on average,
      5.6 +/- 2.1 kg. Relative school bag weight (% of body weight) was higher for boys
      and underweight adolescents compared to their counterparts. Neither absolute nor
      relative school bag weight differed by mode of transport to school. CONCLUSIONS:
      School bag weight was perceived a barrier to ATS and was a greater perceived
      barrier among users of motorized versus active transport. Perceptions of school
      bag weights should be considered in future ATS interventions.

PMID- 30241348
TI  - Characterization of Precursor-Dependent Steroidogenesis in Human Prostate Cancer
      Models.
AB  - Castration-resistant prostate tumors acquire the independent capacity to generate
      androgens by upregulating steroidogenic enzymes or using steroid precursors
      produced by the adrenal glands for continued growth and sustainability. The
      formation of steroids was measured by liquid chromatography-mass spectrometry in
      LNCaP and 22Rv1 prostate cancer cells, and in human prostate tissues, following
      incubation with steroid precursors (22-OH-cholesterol, pregnenolone, 17-OH
      pregnenolone, progesterone, 17-OH-progesterone). Pregnenolone, progesterone, 17
      OH-pregnenolone, and 17-OH-progesterone increased C21 steroid (5-pregnan-3,20
      dione, 5-pregnan-3,17-diol-20-one, 5-pregnan-3-ol-20-one) formation in the
      backdoor pathway, and demonstrated a trend of stimulating dihydroepiandrosterone
      or its precursors in the backdoor pathway in LNCaP and 22Rv1 cells. The
      precursors differentially affected steroidogenic enzyme messenger RNA (mRNA)
      expressions in the cell lines. The steroidogenesis following incubation of human
      prostate tissue with 17-OH-pregnenolone and progesterone produced trends similar
      to those observed in cell lines. Interestingly, the formation of C21 steroids
      from classical pathway was not stimulated but backdoor pathway steroids (e.g., 5
      pregnan-3,20-dione, 5-pregnan-3-ol-20-one) were elevated following incubations
      with prostate tissues. Overall, C21 steroids were predominantly formed in the
      classical as well as backdoor pathways, and steroid precursors induced a
      diversion of steroidogenesis to the backdoor pathway in both cell lines and human
      prostate tissue, and influenced adaptive steroidogenesis to form C21 steroids.

PMID- 30241349
TI  - Knocking Out the Gene RLS1 Induces Hypersensitivity to Oxidative Stress and
      Premature Leaf Senescence in Rice.
AB  - Improving a plant's level of tolerance to oxidative stress can frequently also
      enhance its tolerance to several other abiotic stresses. Here, a screen of a
      japonica type rice T-DNA insertion mutant library identified a highly oxidative
      stress-sensitive mutant. The line exhibited premature leaf senescence, starting
      at the three-leaf stage, and the symptoms were particularly severe from the five
      leaf stage onwards. The leaves progressively lost chlorophyll, suffered protein
      degradation and were compromised with respect to their photosynthetic activity;
      their leaf mesophyll and bulliform cells became shrunken, and several senescence
      associated genes (SAGs), senescence-associated transcription factor genes (SATFs)
      and autophagy-related genes (ATGs) were progressively up-regulated. The product
      of the gene inactivated by the mutation, identified via positional cloning, was
      putatively a ubiquitin-conjugating enzyme. The gene was denoted here as RLS1
      (reactive oxygen species-sensitive leaf senescence1). The phenotype of plants in
      which RLS1 was knocked down using RNA interference was comparable to that of the
      rls1 mutant. A comparative analysis of the knock-out line and the wild type
      leaves showed that the former accumulated more hydrogen peroxide and more
      malondialdehyde, expressed a heightened level of superoxide dismutase activity
      and a decreased level of catalase activity, and exhibited an altered
      transcriptional profile with respect to several SAGs, SATFs and ATGs, and that
      these effects were magnified when the plants were exposed to oxidative stress.
      The product of RLS1 is presumed to be a critical component of the rice oxidative
      stress response and is involved in ROS (reactive oxygen species)-mediated leaf
      senescence.

PMID- 30241350
TI  - Immunogenicity of a Bivalent Non-Purified Recombinant Vaccine against Botulism in
      Cattle.
AB  - Botulism is a potentially fatal intoxication caused by botulinum neurotoxins
      (BoNTs) produced mainly by Clostridium botulinum. Vaccination against BoNT
      serotypes C and D is the main procedure to control cattle botulism. Current
      vaccines contain formaldehyde-inactivated native BoNTs, which have a time
      consuming production process and pose safety risks. The development of non-toxic
      recombinant vaccines has helped to overcome these limitations. This study aims to
      evaluate the humoral immune response generated by cattle immunized with non
      purified recombinant fragments of BoNTs C and D. Cattle were vaccinated in a two
      dose scheme with 100, 200 and 400 ug of each antigen, with serum sampling on days
      0, 56, 120, and 180 after vaccination. Animals who received either 200 or 400 MUg
      of both antigens induced titers higher than the minimum required by the Brazilian
      ministry of Agriculture, Livestock and Food Supply and achieved 100% (8/8)
      seroconversion rate. Animals vaccinated with commercial toxoid vaccine had only a
      75% (6/8) seroconversion rate for both toxins. Animals that received doses
      containing 400 ug of recombinant protein were the only ones to maintain titers
      above the required level up until day 120 post-vaccination, and to achieve 100%
      (8/8) seroconversion for both toxins. In conclusion, 400 ug the recombinant
      Escherichia coli cell lysates supernatant was demonstrated to be an affordable
      means of producing an effective and safe botulism vaccine for cattle.

PMID- 30241351
TI  - Dehydroepiandrosterone Ameliorates Abnormal Mitochondrial Dynamics and Mitophagy
      of Cumulus Cells in Poor Ovarian Responders.
AB  - Mitochondrial dysfunction is related to reproductive decline in humans, with
      consequences for in vitro fertilization (IVF). We assessed whether
      dehydroepiandrosterone (DHEA) could regulate mitochondrial homeostasis and
      mitophagy of cumulus cells (CCs) in poor ovarian responders (PORs). A total of 66
      women who underwent IVF treatment at the Reproductive Medicine Center of
      Kaohsiung Veterans General Hospital were included in this study. Twenty-eight
      normal ovarian responders (NOR) and 38 PORs were enrolled. PORs were assigned to
      receive DHEA supplementation (n = 19) or not (n = 19) before IVF cycles. DHEA
      prevents mitochondrial dysfunction by decreasing the activation of DNM1L and MFF,
      and increasing MFN1 expression. Downregulation of PINK1 and PRKN occurred after
      DHEA treatment, along with increased lysosome formation. DHEA not only promoted
      mitochondrial mass but also improved mitochondrial homeostasis and dynamics in
      the CCs of POR. We also observed effects of alterations in mRNAs known to
      regulate mitochondrial dynamics and mitophagy in the CCs of POR. DHEA may prevent
      mitochondrial dysfunction through regulating mitochondrial homeostasis and
      mitophagy.

PMID- 30241352
TI  - A Review of Non-Pharmacological Treatments for Pain Management in Newborn
      Infants.
AB  - Pain is a major problem in sick newborn infants, especially for those needing
      intensive care. Pharmacological pain relief is the most commonly used, but might
      be ineffective and has side effects, including long-term neurodevelopmental
      sequelae. The effectiveness and safety of alternative analgesic methods are
      ambiguous. The objective was to review the effectiveness and safety of non
      pharmacological methods of pain relief in newborn infants and to identify those
      that are the most effective. PubMed and Google Scholar were searched using the
      terms: "infant", "premature", "pain", "acupuncture", "skin-to-skin contact",
      "sucrose", "massage", "musical therapy" and 'breastfeeding'. We included 24
      studies assessing different methods of non-pharmacological analgesic techniques.
      Most resulted in some degree of analgesia but many were ineffective and some were
      even detrimental. Sucrose, for example, was often ineffective but was more
      effective than music therapy, massage, breast milk (for extremely premature
      infants) or non-invasive electrical stimulation acupuncture. There were also
      conflicting results for acupuncture, skin-to-skin care and musical therapy. Most
      non-pharmacological methods of analgesia provide a modicum of relief for preterm
      infants, but none are completely effective and there is no clearly superior
      method. Study is also required to assess potential long-term consequences of any
      of these methods.

PMID- 30241353
TI  - All-Cause and Cancer Mortality Trends in Macheng, China (1984-2013): An Age
      Period-Cohort Analysis.
AB  - The aim was to study the variation trends of all-cause and cancer mortality
      during 1984-2013 in Macheng City, China. The mortality data were collected from
      Macheng City disease surveillance points system and Hubei Center for Disease
      Control and Prevention. The model life table system was used to adjust mortality
      rates due to an under-reporting problem. An age-period-cohort model and intrinsic
      estimator algorithm were used to estimate the age effect, period effect, and
      cohort effect of all-cause mortality and cancer mortality for males and females.
      Age effect of all-cause mortality for both sexes increased with age, while the
      age effect of cancer mortality for both sexes reached a peak at the age group of
      55-59 years old and then decreased. The relative risks (RRs) of all-cause
      mortality for males and females declined with the period and decreased by 51.13%
      and 63.27% during the whole study period, respectively. Furthermore, the period
      effect of cancer mortality in both sexes decreased at first and then increased.
      The cohort effect of all-cause and cancer mortality for both sexes born after
      1904 presented the pattern of "rise first and then fall," and decreased by 82.18%
      and 90.77% from cohort 1904-1908 to 1989-1993, respectively; especially, the risk
      of all-cause and cancer mortality for both sexes born before 1949 was much higher
      than that for those born after 1949.

PMID- 30241356
TI  - An Automation System for Controlling Streetlights and Monitoring Objects Using
      Arduino.
AB  - We present an Arduino-based automation system to control the streetlights based
      on solar rays and object's detection. We aim to design various systems to achieve
      the desired operations, which no longer require time-consuming manual switching
      of the streetlights. The proposed work is accomplished by using an Arduino
      microcontroller, a light dependent resistor (LDR) and infrared-sensors while, two
      main contributions are presented in this work. Firstly, we show that the
      streetlights can be controlled based on the night and object's detection. In
      which the streetlights automatically turn to DIM state at night-time and turn to
      HIGH state on object's detection, while during day-time the streetlights will
      remain OFF. Secondly, the proposed automated system is further extended to skip
      the DIM condition at night time, and streetlights turn ON based on the objects'
      detection only. In addition, an automatic door system is introduced to improve
      the safety measurements, and most importantly, a counter is set that will count
      the number of objects passed through the road. The proposed systems are designed
      at lab-scale prototype to experimentally validate the efficiency, reliability,
      and low-cost of the systems. We remark that the proposed systems can be easily
      tested and implemented under real conditions at large-scale in the near future,
      that will be useful in the future applications for automation systems and smart
      homes.

PMID- 30241354
TI  - Ruthenium-Based Catalytic Systems Incorporating a Labile Cyclooctadiene Ligand
      with N-Heterocyclic Carbene Precursors for the Atom-Economic Alcohol Amidation
      Using Amines.
AB  - Transition-metal-catalyzed amide-bond formation from alcohols and amines is an
      atom-economic and eco-friendly route. Herein, we identified a highly active in
      situ N-heterocyclic carbene (NHC)/ruthenium (Ru) catalytic system for this amide
      synthesis. Various substrates, including sterically hindered ones, could be
      directly transformed into the corresponding amides with the catalyst loading as
      low as 0.25 mol.%. In this system, we replaced the p-cymene ligand of the Ru
      source with a relatively labile cyclooctadiene (cod) ligand so as to more
      efficiently obtain the corresponding poly-carbene Ru species. Expectedly, the
      weaker cod ligand could be more easily substituted with multiple mono-NHC
      ligands. Further high-resolution mass spectrometry (HRMS) analyses revealed that
      two tetra-carbene complexes were probably generated from the in situ catalytic
      system.

PMID- 30241355
TI  - Maintaining Genome Integrity during Seed Development in Phaseolus vulgaris L.:
      Evidence from a Transcriptomic Profiling Study.
AB  - The maintenance of genome integrity is crucial in seeds, due to the constant
      challenge of several endogenous and exogenous factors. The knowledge concerning
      DNA damage response and chromatin remodeling during seed development is still
      scarce, especially in Phaseolus vulgaris L. A transcriptomic profiling of the
      expression of genes related to DNA damage response/chromatin remodeling
      mechanisms was performed in P. vulgaris seeds at four distinct developmental
      stages, spanning from late embryogenesis to seed desiccation. Of the 14,001
      expressed genes identified using massive analysis of cDNA ends, 301 belong to the
      DNA MapMan category. In late embryogenesis, a high expression of genes related to
      DNA damage sensing and repair suggests there is a tight control of DNA integrity.
      At the end of filling and the onset of seed dehydration, the upregulation of
      genes implicated in sensing of DNA double-strand breaks suggests that genome
      integrity is challenged. The expression of chromatin remodelers seems to imply a
      concomitant action of chromatin remodeling with DNA repair machinery, maintaining
      genome stability. The expression of genes related to nucleotide excision repair
      and chromatin structure is evidenced during the desiccation stage. An overview of
      the genes involved in DNA damage response and chromatin remodeling during P.
      vulgaris seed development is presented, providing insights into the mechanisms
      used by developing seeds to cope with DNA damage.

PMID- 30241357
TI  - Uptake and Distribution of Fenoxanil-Loaded Mesoporous Silica Nanoparticles in
      Rice Plants.
AB  - Mesoporous silica nanoparticles (MSNs) can be used as carriers to deliver
      pesticides into plants, which is considered to be one method of improving the
      efficacy of pesticide usage in agricultural production. In the present work, MSNs
      with an average diameter of 258.1 nm were synthesized and loaded with Fenoxanil.
      The structure of the nanocarriers was observed by scanning electron microscopy.
      The loading content of Fenoxanil-loaded MSNs was investigated. After rice plants
      in a hydroponic system were treated with loaded MSNs, the concentrations of
      Fenoxanil in different samples were determined using high-performance liquid
      chromatography-tandem mass spectrometry. The results suggested that rice plants
      can absorb MSNs from water through their roots, and the dosage has almost no
      effect on the distribution of Fenoxanil in rice plants. The application of
      pesticide-loaded nanoparticles in a hydroponic system poses a low risk of
      Fenoxanil accumulation in rice.

PMID- 30241359
TI  - Polymyalgia Rheumatica (PMR) with Normal Values of Both Erythrocyte Sedimentation
      Rate (ESR) and C-Reactive Protein (CRP) Concentration at the Time of Diagnosis in
      a Centenarian Man: A Case Report.
AB  - The possibility that polymyalgia rheumatica (PMR) can be diagnosed when both ESR
      and CRP are normal at the time of diagnosis and before therapy with
      glucocorticoids, has been often discussed in the literature. We present a case
      report of a 100-year-old Caucasian man referred to our outpatient clinic,
      complaining of chronic pain in the shoulder and hip girdle associated with normal
      values of both ESR (21 mm/1st hour) and CRP (4 mg/dL). In the previous four
      months, several anti-inflammatory drugs and painkillers associated with
      physiotherapy treatments gave no significant improvement in pain and self-care.
      After an ultrasound (US) and an 18-fluorodeoxyglucose positron emission
      tomography associated with total body computed tomography (18-FDG PET/CT)
      examination, PMR was diagnosed and he started therapy with 17.5 mg prednisone,
      obtaining a fast improvement in pain and self-care. After 10 months of tapering,
      he stopped prednisone without relapse. During a 3-year follow-up, no alternative
      diagnosis was done. When a patient complains of chronic bilateral shoulder and
      hip girdle pain associated with normal inflammatory indices, it is reasonable to
      think in the first instance that this person is not suffering from PMR. Moreover,
      the possibility that PMR may onset in a centenarian person, is exceptional. In
      our patient, when we piece the puzzle together, the diagnosis of PMR was the most
      possible one.

PMID- 30241358
TI  - Mendelian Randomization Studies of Coffee and Caffeine Consumption.
AB  - Habitual coffee and caffeine consumption has been reported to be associated with
      numerous health outcomes. This perspective focuses on Mendelian Randomization
      (MR) approaches for determining whether such associations are causal. Genetic
      instruments for coffee and caffeine consumption are described, along with key
      concepts of MR and particular challenges when applying this approach to studies
      of coffee and caffeine. To date, at least fifteen MR studies have investigated
      the causal role of coffee or caffeine use on risk of type 2 diabetes,
      cardiovascular disease, Alzheimer's disease, Parkinson's disease, gout,
      osteoarthritis, cancers, sleep disturbances and other substance use. Most studies
      provide no consistent support for a causal role of coffee or caffeine on these
      health outcomes. Common study limitations include low statistical power,
      potential pleiotropy, and risk of collider bias. As a result, in many cases a
      causal role cannot confidently be ruled out. Conceptual challenges also arise
      from the different aspects of coffee and caffeine use captured by current genetic
      instruments. Nevertheless, with continued genome-wide searches for coffee and
      caffeine related loci along with advanced statistical methods and MR designs, MR
      promises to be a valuable approach to understanding the causal impact that coffee
      and caffeine have in human health.

PMID- 30241361
TI  - The Structure and Phenology of Non-Native Scolytine Beetle Communities in Coffee
      Plantations on Kaua'i.
AB  - Populations and communities are known to respond to abiotic conditions, but the
      forces determining the distribution of particular insect pests are sometimes
      overlooked in the process of developing control methods. Bark and ambrosia
      beetles (Curculionidae: Scolytinae) are important pests of crops, forestry, and
      ecosystems worldwide, yet the factors that influence their success are unknown
      for many species. The Hawaiian archipelago is host to over three dozen invasive
      scolytines, many of which occur on Kaua'i and are pests of agriculture. We
      analyzed scolytine community dynamics at two coffee estates: a hand-harvested
      site in a tropical wet forest and a mechanically harvested site in a tropical dry
      savanna. Our regression analyses show overall scolytine abundance was negatively
      correlated with rainfall, as were four species: the tropical nut borer
      (Hypothenemus obscurus), H. brunneus, Cryphalus longipilus, and Xyleborinus
      andrewesi. These relationships contributed to the compositions of the communities
      being markedly dissimilar despite having the same species richness. Multivariate
      analysis found no influence from temperature or harvest method on community
      dynamics. This information can be valuable for the timing of pest control
      methods, for predicting the success of possible new scolytine arrivals on Kaua'i,
      and for forecasting how these species may spread with climate change.

PMID- 30241360
TI  - Health Risk of Polonium 210 Ingestion via Drinking Water: An Experience of
      Malaysia.
AB  - The presence of toxic polonium-210 (Po-210) in the environment is due to the
      decay of primordial uranium-238. Meanwhile, several studies have reported
      elevated Po-210 radioactivity in the rivers around the world due to both natural
      and anthropogenic factors. However, the primary source of Po-210 in Langat River,
      Malaysia might be the natural weathering of granite rock along with mining,
      agriculture and industrial activities. Hence, this is the first study to
      determine the Po-210 activity in the drinking water supply chain in the Langat
      River Basin to simultaneously predict the human health risks of Po-210 ingestion.
      Therefore, water samples were collected in 2015-2016 from the four stages of the
      water supply chain to analyze by Alpha Spectrometry. Determined Po-210 activity,
      along with the influence of environmental parameters such as time-series
      rainfall, flood incidents and water flow data (2005-2015), was well within the
      maximum limit for drinking water quality standard proposed by the Ministry of
      Health Malaysia and World Health Organization. Moreover, the annual effective
      dose of Po-210 ingestion via drinking water supply chain indicates an acceptable
      carcinogenic risk for the populations in the Langat Basin at 95% confidence
      level; however, the estimated annual effective dose at the basin is higher than
      in many countries. Although several studies assume the carcinogenic risk of Po
      210 ingestion to humans for a long time even at low activity, however, there is
      no significant causal study which links Po-210 ingestion via drinking water and
      cancer risk of the human. Since the conventional coagulation method is unable to
      remove Po-210 entirely from the treated water, introducing a two-layer water
      filtration system at the basin can be useful to achieve SDG target 6.1 of
      achieving safe drinking water supplies well before 2030, which might also be
      significant for other countries.

PMID- 30241363
TI  - Extended Line Map-Based Precise Vehicle Localization Using 3D LIDAR.
AB  - An Extended Line Map (ELM)-based precise vehicle localization method is proposed
      in this paper, and is implemented using 3D Light Detection and Ranging (LIDAR). A
      binary occupancy grid map in which grids for road marking or vertical structures
      have a value of 1 and the rest have a value of 0 was created using the
      reflectivity and distance data of the 3D LIDAR. From the map, lines were detected
      using a Hough transform. After the detected lines were converted into the node
      and link forms, they were stored as a map. This map is called an extended line
      map, of which data size is extremely small (134 KB/km). The ELM-based
      localization is performed through correlation matching. The ELM is converted back
      into an occupancy grid map and matched to the map generated using the current 3D
      LIDAR. In this instance, a Fast Fourier Transform (FFT) was applied as the
      correlation matching method, and the matching time was approximately 78 ms (based
      on MATLAB). The experiment was carried out in the Gangnam area of Seoul, South
      Korea. The traveling distance was approximately 4.2 km, and the maximum traveling
      speed was approximately 80 km/h. As a result of localization, the root mean
      square (RMS) position errors for the lateral and longitudinal directions were
      0.136 m and 0.223 m, respectively.

PMID- 30241362
TI  - The Effects of High Fat Diet-Induced Stress on Olfactory Sensitivity, Behaviors,
      and Transcriptional Profiling in Drosophila melanogaster.
AB  - High-fat diet (HFD) often causes obesity and it has detrimental effects on the
      sensory system. In particular, sensory-mediated responses are crucial for
      maintaining energy balance, as they are involved in a metabolic regulation;
      however, there is still no clear explanation about the relationship between HFD
      induced stress and sensory system. To gain insight on how HFD-induced stress
      affects olfactory sensitivity and behavioral responses, we have used a Drosophila
      melanogaster model for olfactory and nutrient-related signaling and accessed
      physiological, behavioral, and transcriptional changes. We demonstrated that
      lifespan and climbing ability in HFD-treated flies decreased and that olfactory
      sensitivity and behavioral responses to odorants were changed. Olfactory
      sensitivity to eight of ten odorants after 14 days on HFD treatment were reduced,
      while behavioral attraction was increased to benzaldehyde in flies that were
      treated with HFD. This behavioral and physiological modification in HFD-treated
      flies for 14 days was accompanied by a significant decrease in DmOrco gene
      expression in a peripheral olfactory organ, suggesting that is could be involved
      in the action of metabolic and sensory signal. Gene expression profiles of
      antennae showed significant differences on the olfactory receptors, odorant
      binding proteins, and insulin signaling. Our results suggested that olfactory
      sensitivity and behavioral responses to HFD-induced stress are mediated through
      olfactory and nutrient-related signaling pathways.

PMID- 30241364
TI  - Predictive Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Head and
      Neck Squamous Cell Carcinoma.
AB  - This study assessed the significance of the neutrophil-to-lymphocyte ratio (NLR)
      in head and neck squamous cell carcinoma (HNSCC), and the relationships of the
      NLR with the aldehyde dehydrogenase 1 (ALDH1) level in tumors and the proportion
      of myeloid-derived suppressor cells (MDSCs) in the peripheral circulation. In
      total, 227 HNSCC patients who had received curative treatment at our hospital
      were enrolled into the present study. The NLR of each HNSCC patient before
      treatment was calculated. The associations of NLR with various
      clinicopathological parameters and prognoses were then examined. In addition,
      correlations between the proportion of MDSCs and level of ALDH1 with the NLR were
      assessed. Our data revealed that an elevated NLR was significantly correlated
      with the risk of developing locoregional recurrence and with a reduced overall
      survival in HNSCC patients. Multivariate analyses revealed that the NLR
      pretreatment and surgical resection were significantly correlated with the rate
      of treatment failure and the overall survival rate in HNSCC patients.
      Furthermore, the levels of ALDH1 in tumors and MDSCs in the peripheral
      circulation were significantly correlated with the prognosis of HNSCC, and the
      NLR was positively correlated with MDSC levels in the circulation and ALDH1
      staining intensity in tumor specimens. In conclusion, the NLR has power in
      predicting the expression of ALDH1 in tumors, the circulating level of MDSCs, and
      the prognosis in HNSCC. We suggest that the NLR is an important biomarker that
      can assist the clinician and patient in making informed decisions regarding
      treatment options for HNSCC patients.

PMID- 30241365
TI  - Three Landmark Optimization Strategies for Mobile Robot Visual Homing.
AB  - Visual homing is an attractive autonomous mobile robot navigation technique,
      which only uses vision sensors to guide the robot to the specified target
      location. Landmark is the only input form of the visual homing approaches, which
      is usually represented by scale-invariant features. However, the landmark
      distribution has a great impact on the homing performance of the robot, as
      irregularly distributed landmarks will significantly reduce the navigation
      precision. In this paper, we propose three strategies to solve this problem. We
      use scale-invariant feature transform (SIFT) features as natural landmarks, and
      the proposed strategies can optimize the landmark distribution without over
      eliminating landmarks or increasing calculation amount. Experiments on both
      panoramic image databases and a real mobile robot have verified the effectiveness
      and feasibility of the proposed strategies.

PMID- 30241366
TI  - Synthesis and Characterization of Poly(Vinyl Alcohol)-Chitosan-Hydroxyapatite
      Scaffolds: A Promising Alternative for Bone Tissue Regeneration.
AB  - Scaffolds can be considered as one of the most promising treatments for bone
      tissue regeneration. Herein, blends of chitosan, poly(vinyl alcohol), and
      hydroxyapatite in different ratios were used to synthesize scaffolds via freeze
      drying. Mechanical tests, FTIR, swelling and solubility degree, DSC, morphology,
      and cell viability were used as characterization techniques. Statistical
      significance of the experiments was determined using a two-way analysis of
      variance (ANOVA) with p < 0.05. Crosslinked and plasticized scaffolds absorbed
      five times more water than non-crosslinked and plasticized ones, which is an
      indicator of better hydrophilic features, as well as adequate resistance to water
      without detriment of the swelling potential. Indeed, the tested mechanical
      properties were notably higher for samples which were undergone to crosslinking
      and plasticized process. The presence of chitosan is determinant in pore
      formation and distribution which is an imperative for cell communication. Uniform
      pore size with diameters ranging from 142 to 519 um were obtained, a range that
      has been described as optimal for bone tissue regeneration. Moreover,
      cytotoxicity was considered as negligible in the tested conditions, and viability
      indicates that the material might have potential as a bone regeneration system.

PMID- 30241367
TI  - The Physical Activity and Sedentary Behaviour Patterns of Children in
      Kindergarten and Grade 2.
AB  - Accompanying the transition from early to middle childhood are substantial
      changes in children's educational and recreational circumstances. These changes
      may affect physical activity levels. This study examined levels of physical
      activity and sedentary behaviours in kindergarten (age range 5-6 years) and grade
      2 (age range 7-8 years). Participants were 96 kindergarten children recruited in
      the 2010-2011 and 2011-2012 school years and 94 grade 2 children recruited in the
      2012-2013 and 2013-2014 school years. A sub-cohort of children was tracked
      longitudinally from kindergarten to grade 2. Accelerometers were used to measure
      physical activity and sedentary behaviour. Independent t-tests revealed that
      children in grade 2 spent significantly less time engaged in physical activity
      compared to those in kindergarten (292 min/day compared with 354 min/day) and
      more in sedentary behaviours (443 min/day compared with 368 min/day). For the
      longitudinal sample, the pattern was similar. Repeated measures ANOVA revealed a
      significant decrease in physical activity levels (364 min/day to 292 min/day) and
      a significant increase in sedentary behaviour (368 min/day to 435 min/day) over
      time. There is a critical need to invest in strategies to maintain higher levels
      of physical activity across the primary years and reduce sedentary time, since
      these behaviours affect health outcomes.

PMID- 30241368
TI  - B Chromosomes of the Asian Seabass (Lates calcarifer) Contribute to Genome
      Variations at the Level of Individuals and Populations.
AB  - The Asian seabass (Lates calcarifer) is a bony fish from the Latidae family,
      which is widely distributed in the tropical Indo-West Pacific region. The
      karyotype of the Asian seabass contains 24 pairs of A chromosomes and a variable
      number of AT- and GC-rich B chromosomes (Bchrs or Bs). Dot-like shaped and
      nucleolus-associated AT-rich Bs were microdissected and sequenced earlier. Here
      we analyzed DNA fragments from Bs to determine their repeat and gene contents
      using the Asian seabass genome as a reference. Fragments of 75 genes, including
      an 18S rRNA gene, were found in the Bs; repeats represented 2% of the Bchr
      assembly. The 18S rDNA of the standard genome and Bs were similar and enriched
      with fragments of transposable elements. A higher nuclei DNA content in the male
      gonad and somatic tissue, compared to the female gonad, was demonstrated by flow
      cytometry. This variation in DNA content could be associated with the intra
      individual variation in the number of Bs. A comparison between the copy number
      variation among the B-related fragments from whole genome resequencing data of
      Asian seabass individuals identified similar profiles between those from the
      South-East Asian/Philippines and Indian region but not the Australian ones. Our
      results suggest that Bs might cause variations in the genome among the
      individuals and populations of Asian seabass. A personalized copy number approach
      for segmental duplication detection offers a suitable tool for population-level
      analysis across specimens with low coverage genome sequencing.

PMID- 30241369
TI  - The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating
      Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer.
AB  - Individuals at risk (IAR) of familial pancreatic cancer (FPC) are good candidates
      for screening. Unfortunately, neither reliable imaging modalities nor biomarkers
      are available to detect high-grade precursor lesions or early cancer. Circulating
      levels of candidate biomarkers LCN2, TIMP1, Glypican-1, RNU2-1f, and miRNA-196b
      were analyzed in 218 individuals with sporadic pancreatic ductal adenocarcinoma
      (PDAC, n = 50), FPC (n = 20), chronic pancreatitis (n = 10), IAR with relevant
      precursor lesions (n = 11) or non-relevant lesions (n = 5), 20 controls, and IAR
      with (n = 51) or without (n = 51) lesions on pancreatic imaging. In addition,
      corresponding duodenal juice samples were analyzed for Glypican-1 (n = 144)
      enrichment and KRAS mutations (n = 123). The panel miR-196b/LCN2/TIMP1 could
      distinguish high-grade lesions and stage I PDAC from controls with absolute
      specificity and sensitivity. In contrast, Glypican-1 enrichment in serum exosomes
      and duodenal juice was not diagnostic. KRAS mutations in duodenal juice were
      detected in 9 of 12 patients with PDAC and only 4 of 9 IAR with relevant
      precursor lesions. IAR with lesions on imaging had elevated miR-196b/LCN2/TIMP1
      levels (p = 0.0007) and KRAS mutations in duodenal juice (p = 0.0004)
      significantly more often than IAR without imaging lesions. The combination miR
      196b/LCN2/TIMP1 might be a promising biomarker set for the detection of high
      grade PDAC precursor lesions in IAR of FPC families.

PMID- 30241371
TI  - Combined Use of N-Palmitoyl-Glycine-Histidine Gel and Several Penetration
      Enhancers on the Skin Permeation and Concentration of Metronidazole.
AB  - N-Palmitoyl-Glycine-Histidine (Pal-GH) is a novel low molecular weight gelator.
      In our previous report, ivermectin, a lipophilic drug, was effectively delivered
      to skin tissue after topical application with Pal-GH as a spray gel formulation,
      and a much higher skin concentration was confirmed than with the administration
      of a conventional oral formulation. The objective of this study was to increase
      the skin permeation of metronidazole (MTZ), a hydrophilic drug, after the topical
      application of Pal-GH gel. An evaluation of the combined effect of chemical
      penetration enhancers (CPEs), such as isopropyl myristate (IPM), propylene glycol
      (PG), ethanol, diethylene glycol monoethyl ether, and dimethyl sulfoxide (DMSO),
      on skin permeation was also conducted. We found that a 5% Pal-GH gel containing
      1% MTZ (F5MTZ) exhibited a 2.7-fold higher MTZ permeation through excised
      hairless rat skin than its solution. Furthermore, F5PG-MTZ and F5IPM-MTZ further
      increased the skin permeation of MTZ when compared to F5MTZ. Interestingly, F5PG
      MTZ enhanced the skin penetration of MTZ, although no enhancement effect was
      observed for an MTZ solution containing PG. Thus, a Pal-GH formulation containing
      PG and IPM may enhance the skin permeation of MTZ.

PMID- 30241370
TI  - Role of the Genetic Background in Resistance to Plant Viruses.
AB  - In view of major economic problems caused by viruses, the development of
      genetically resistant crops is critical for breeders but remains limited by the
      evolution of resistance-breaking virus mutants. During the plant breeding
      process, the introgression of traits from Crop Wild Relatives results in a
      dramatic change of the genetic background that can alter the resistance
      efficiency or durability. Here, we conducted a meta-analysis on 19 Quantitative
      Trait Locus (QTL) studies of resistance to viruses in plants. Frequent epistatic
      effects between resistance genes indicate that a large part of the resistance
      phenotype, conferred by a given QTL, depends on the genetic background. We next
      reviewed the different resistance mechanisms in plants to survey at which stage
      the genetic background could impact resistance or durability. We propose that the
      genetic background may impair effector-triggered dominant resistances at several
      stages by tinkering the NB-LRR (Nucleotide Binding-Leucine-Rich Repeats) response
      pathway. In contrast, effects on recessive resistances by loss-of-susceptibility
      such as eIF4E-based resistances-are more likely to rely on gene redundancy among
      the multigene family of host susceptibility factors. Finally, we show how the
      genetic background is likely to shape the evolution of resistance-breaking
      isolates and propose how to take this into account in order to breed plants with
      increased resistance durability to viruses.

PMID- 30241372
TI  - Differential Accumulation of Anthocyanins in Dendrobium officinale Stems with Red
      and Green Peels.
AB  - Dendrobium officinale stems, including red and green stems, are widely used as a
      dietary supplement to develop nutraceutical beverages and food products. However,
      there is no detailed information on pigment composition of red and green stems.
      Here, we investigated the content and composition of pigments in red and green
      stems by Ultra-performance liquid chromatography quadrupole time-of-flight mass
      spectrometry and assessed the differential accumulation of anthocyanins at the
      molecular level. The color of peels in red stems was caused by the presence of
      anthocyanins in epidermal cells unlike the peels of green stems. The glucoside
      derivatives delphinidin and cyanidin are responsible for the red color. Within
      the D. officinale anthocyanidin biosynthetic pathway, DoANS and DoUFGT, coding
      for anthocyanidin synthase and UDP-glucose flavonoid-3-O-glucosyltransferase,
      respectively, are critical regulatory genes related to the differential
      accumulation of anthocyanidin. These findings provide a more complete profile of
      pigments, especially anthocyanin, in D. officinale stems, and lay a foundation
      for producing functional foods.

PMID- 30241374
TI  - Design, Synthesis and Docking Studies of Novel Macrocyclic Pentapeptides as
      Anticancer Multi-Targeted Kinase Inhibitors.
AB  - A series of macrocyclic pyrido-pentapeptide candidates 2-6 were synthesized by
      using N,N-bis-[1-carboxy-2-(benzyl)]-2,6-(diaminocarbonyl)pyridine 1a,b as
      starting material. Structures of the newly synthesized compounds were established
      by IR, 1H and 13C-NMR, and MS spectral data and elemental analysis. The in-vitro
      cytotoxicity activity was investigated for all compounds against MCF-7 and HepG-2
      cell lines and the majority of the compounds showed potent anticancer activity
      against the tested cell lines in comparison with the reference drugs. Out of the
      macrocyclic pyrido-pentapeptide based compounds, 5c showed encouraging inhibitory
      activity on MCF-7 and HepG-2 cell lines with IC50 values 9.41 +/- 1.25 and 7.53
      +/- 1.33 MUM, respectively. Interestingly, 5c also demonstrated multitarget
      profile and excellent inhibitory activity towards VEGFR-2, CDK-2 and PDGFRbeta
      kinases. Furthermore, molecular modeling studies of the compound 5c revealed its
      possible binding modes into the active sites of those kinases.

PMID- 30241375
TI  - Recent Advances in Synthesis of 4-Arylcoumarins.
AB  - 4-Arylcoumarins (4-aryl-2H-1-benzopyran-2-one), also known as neoflavones,
      comprise a minor subclass of naturally occurring flavonoids. Because of their
      broad-spectrum biological activities, arylcoumarins have been attracting the
      attention of the organic and medicinal chemistry communities, and are considered
      as an important privileged scaffold. Since the development of Pechmann
      condensation, a classical acid-catalyzed condensation between phenol and beta
      keto-carboxylic acid, several versatile and efficient synthetic approaches for 4
      arylcoumarins have been reported. This review summarizes recent advances in the
      synthesis of the 4-arylcoumarin scaffold by classifying them based on the final
      bond-formation type. In particular, synthetic methods executed under mild and
      highly efficient conditions, such as solvent-free reactions and transition metal
      catalysis, are highlighted.

PMID- 30241376
TI  - Correction: Chatterjee, A.; et al. Transition Metal Hollow Nanocages as Promising
      Cathodes for the Long-Term Cyclability of Li-O2 Batteries. Nanomaterials 2018, 8,
      308.
AB  - The authors wish to add the following information to this paper [...].

PMID- 30241373
TI  - Control of DNA Replication Initiation by Ubiquitin.
AB  - Eukaryotic cells divide by accomplishing a program of events in which the
      replication of the genome is a fundamental part. To ensure all cells have an
      accurate copy of the genome, DNA replication occurs only once per cell cycle and
      is controlled by numerous pathways. A key step in this process is the initiation
      of DNA replication in which certain regions of DNA are marked as competent to
      replicate. Moreover, initiation of DNA replication needs to be coordinated with
      other cell cycle processes. At the molecular level, initiation of DNA replication
      relies, among other mechanisms, upon post-translational modifications, including
      the conjugation and hydrolysis of ubiquitin. An example is the precise control of
      the levels of the DNA replication initiation protein Cdt1 and its inhibitor
      Geminin by ubiquitin-mediated proteasomal degradation. This control ensures that
      DNA replication occurs with the right timing during the cell cycle, thereby
      avoiding re-replication events. Here, we review the events that involve ubiquitin
      signalling during DNA replication initiation, and how they are linked to human
      disease.

PMID- 30241377
TI  - Development of Validated Methods and Quantification of Curcuminoids and Curcumin
      Metabolites and Their Pharmacokinetic Study of Oral Administration of Complete
      Natural Turmeric Formulation (CureitTM) in Human Plasma via UPLC/ESI-Q-TOF-MS
      Spectrometry.
AB  - Specific and sensitive ultra-high performance liquid chromatography-quadrupole
      time of flight-mass spectroscopy (UPLC-QTOF-MS) methods have been developed for
      the determination of curcuminoids and curcumin metabolites in human blood plasma.
      The UPLC-QTOF-MS method used a binary solvent delivery system and the
      chromatographic separation was performed on a C-18 (2.1 * 50 mm; 1.7 um) column.
      Mass spectra were obtained on a Waters Xevo G2S Q-TOF mass spectrometer. The
      developed methods to characterize the pharmacokinetics of curcuminoids and
      curcumin metabolites in human blood plasma after an oral administration of
      bioavailable curcumin-CureitTM-were validated. It was found that the complete
      turmeric matrix enhances the concentration of tetrahydrocurcumin (THC),
      hexahydrocurcumin (HHC), octahydrocurcumin (OHC), curcumin-O-glucuronide (COG)
      and curcumin-O-sulfate (COS) in the blood plasma once the product is
      administrated.

PMID- 30241378
TI  - A Plasmonic Chip-Scale Refractive Index Sensor Design Based on Multiple Fano
      Resonances.
AB  - In this paper, multiple Fano resonances preferred in the refractive index sensing
      area are achieved based on sub-wavelength metal-insulator-metal (MIM) waveguides.
      Two slot cavities, which are placed between or above the MIM waveguides, can
      support the bright modes or the dark modes, respectively. Owing to the mode
      interferences, dual Fano resonances with obvious asymmetrical spectral responses
      are achieved. High sensitivity and high figure of merit are investigated by using
      the finite-difference time-domain (FDTD) method. In view of the development of
      chip-scale integrated photonics, two extra slot cavities are successively added
      to the structure, and consequently, three and four ultra-sharp Fano peaks with
      considerable performances are obtained, respectively. It is believed that this
      proposed structure can find important applications in the on-chip optical sensing
      and optical communication areas.

PMID- 30241379
TI  - Identification of Endogenous Control miRNAs for RT-qPCR in T-Cell Acute
      Lymphoblastic Leukemia.
AB  - Optimal endogenous controls enable reliable normalization of microRNA (miRNA)
      expression in reverse-transcription quantitative PCR (RT-qPCR). This is
      particularly important when miRNAs are considered as candidate diagnostic or
      prognostic biomarkers. Universal endogenous controls are lacking, thus candidate
      normalizers must be evaluated individually for each experiment. Here we present a
      strategy that we applied to the identification of optimal control miRNAs for RT
      qPCR profiling of miRNA expression in T-cell acute lymphoblastic leukemia (T-ALL)
      and in normal cells of T-lineage. First, using NormFinder for an iterative
      analysis of miRNA stability in our miRNA-seq data, we established the number of
      control miRNAs to be used in RT-qPCR. Then, we identified optimal control miRNAs
      by a comprehensive analysis of miRNA stability in miRNA-seq data and in RT-qPCR
      by analysis of RT-qPCR amplification efficiency and expression across a variety
      of T-lineage samples and T-ALL cell line culture conditions. We then showed the
      utility of the combination of three miRNAs as endogenous normalizers (hsa-miR-16
      5p, hsa-miR-25-3p, and hsa-let-7a-5p). These miRNAs might serve as first-line
      candidate endogenous controls for RT-qPCR analysis of miRNAs in different types
      of T-lineage samples: T-ALL patient samples, T-ALL cell lines, normal immature
      thymocytes, and mature T-lymphocytes. The strategy we present is universal and
      can be transferred to other RT-qPCR experiments.

PMID- 30241380
TI  - Thymosin Beta-4 and Ciprofloxacin Adjunctive Therapy Improves Pseudomonas
      aeruginosa-Induced Keratitis.
AB  - With increasing multidrug resistance and contraindication for corticosteroid use,
      the goal of this study was to develop thymosin beta-4 (Tbeta4) as an adjunctive
      therapy to antibiotics for the treatment of bacterial keratitis that effectively
      promotes enhanced wound healing, host defense, and inflammation resolution.
      Disease outcome was assessed by clinical score, slit lamp photography, and
      histopathology. Cytokine profile, bacterial load, PMN infiltration, and Griess
      and reactive oxygen species (ROS) levels were determined. Adjunct Tbeta4
      treatment resulted in a significant improvement compared to PBS, Tbeta4, and most
      remarkably, ciprofloxacin, correlating with changes in mediators of inflammation
      and wound healing. Collectively, these data provide evidence that wound healing
      is an essential aspect in the development of new therapies to treat corneal
      infection. Use of adjunctive Tbeta4 provides a more efficacious approach for
      bacterial keratitis by addressing both the infectious pathogen and deleterious
      host response.

PMID- 30241382
TI  - ZKSCAN3 Upregulation and Its Poor Clinical Outcome in Uterine Cervical Cancer.
AB  - Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3) upregulates genes encoding
      proteins involved in cell differentiation, proliferation and apoptosis. ZKSCAN3
      has been reported to be overexpressed in several human cancers such as colorectal
      cancer and prostate cancer and is proposed as a candidate oncoprotein. However,
      the molecular mechanism by which ZKSCAN3 participates in carcinogenesis is
      largely unknown. Here, we evaluated ZKSCAN3 expression in uterine cervical
      cancers (CC) by immunohistochemistry using formalin-fixed, paraffin-embedded
      tissues from 126 biopsy samples from 126 patients. The clinicopathological
      findings were analyzed and compared with ZKSCAN3 expression levels. ZKSCAN3 was
      strongly overexpressed in CCs compared to adjacent non-neoplastic cervical mucosa
      tissues. Moreover, a gene copy number assay showed amplified ZKSCAN3 in CC
      samples. ZKSCAN3 overexpression was also significantly associated with poor
      overall survival of the patients. Overall, our findings indicate that ZKSCAN3
      overexpression is a frequent event in uterine CC and is correlated with a poor
      clinical outcome. ZKSCAN3 could be developed as a molecular marker for prognostic
      prediction and early detection.

PMID- 30241381
TI  - Influence of Eugenia uniflora Extract on Adhesion to Human Buccal Epithelial
      Cells, Biofilm Formation, and Cell Surface Hydrophobicity of Candida spp. from
      the Oral Cavity of Kidney Transplant Recipients.
AB  - This study evaluated the influence of the extract of Eugenia uniflora in adhesion
      to human buccal epithelial cells (HBEC) biofilm formation and cell surface
      hydrophobicity (CSH) of Candida spp. isolated from the oral cavity of kidney
      transplant patients. To evaluate virulence attributes in vitro, nine yeasts were
      grown in the presence and absence of 1000 MUg/mL of the extract. Adhesion was
      quantified using the number of Candida cells adhered to 150 HBEC determined by
      optical microscope. Biofilm formation was evaluated using two methodologies: XTT
      (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) and
      crystal violet assay, and further analyzed by electronic scan microscopy. CSH was
      quantified with the microbial adhesion to hydrocarbons test. We could detect that
      the extract of E. uniflora was able to reduce adhesion to HBEC and CSH for both
      Candida albicans and non-Candida albicansCandida species. We also observed a
      statistically significant reduced ability to form biofilms in biofilm-producing
      strains using both methods of quantification. However, two highly biofilm
      producing strains of Candida tropicalis had a very large reduction in biofilm
      formation. This study reinforces the idea that besides growth inhibition, E.
      uniflora may interfere with the expression of some virulence factors of Candida
      spp. and may be possibly applied in the future as a novel antifungal agent.

PMID- 30241383
TI  - Unravelling the Distribution of Secondary Metabolites in Olea europaea L.:
      Exhaustive Characterization of Eight Olive-Tree Derived Matrices by Complementary
      Platforms (LC-ESI/APCI-MS and GC-APCI-MS).
AB  - In order to understand the distribution of the main secondary metabolites found
      in Olea europaea L., eight different samples (olive leaf, stem, seed, fruit skin
      and pulp, as well as virgin olive oil, olive oil obtained from stoned and
      dehydrated fruits and olive seed oil) coming from a Picudo cv. olive tree were
      analyzed. All the experimental conditions were selected so as to assure the
      maximum coverage of the metabolome of the samples under study within a single
      run. The use of LC and GC with high resolution MS (through different ionization
      sources, ESI and APCI) and the annotation strategies within MetaboScape 3.0
      software allowed the identification of around 150 compounds in the profiles,
      showing great complementarity between the evaluated methodologies. The identified
      metabolites belonged to different chemical classes: triterpenic acids and
      dialcohols, tocopherols, sterols, free fatty acids, and several sub-types of
      phenolic compounds. The suitability of each platform and polarity (negative and
      positive) to determine each family of metabolites was evaluated in-depth,
      finding, for instance, that LC-ESI-MS (+) was the most efficient choice to ionize
      phenolic acids, secoiridoids, flavonoids and lignans and LC-APCI-MS was very
      appropriate for pentacyclic triterpenic acids (MS (-)) and sterols and
      tocopherols (MS (+)). Afterwards, a semi-quantitative comparison of the selected
      matrices was carried out, establishing their typical features (e.g., fruit skin
      was pointed out as the matrix with the highest relative amounts of phenolic
      acids, triterpenic compounds and hydroxylated fatty acids, and seed oil was
      distinctive for its high relative levels of acetoxypinoresinol and tocopherols).

PMID- 30241384
TI  - Developing Efficient Thin Film Temperature Sensors Utilizing Layered Carbon
      Nanotube Films.
AB  - In this paper, we present the fabrication of an efficient thin film temperature
      sensor utilizing chemical vapor deposited carbon nanotube (CNT) film as the
      sensing element on Si substrates, with diamond-like carbon (DLC):Ni as a catalyst
      in assisting CNT growth. The fabricated sensor showed good electrical response
      with change in temperature. Relative linear change in resistance of 18.4% for an
      increase in temperature from 22  degrees C to 200  degrees C was achieved.
      Various characterizing techniques, such as scanning electron microscopy (SEM) and
      Raman spectroscopy, were used to characterize the films. In an effort to study
      device performance, van der Pauw and Hall measurements were carried out to study
      the dependence of resistance on temperature and magnetic fields. Temperature
      coefficient of resistance of the sensor was calculated as 1.03 * 10-3/ degrees C.
      All implications arising from the study are presented. The results establish the
      aptness of the as-grown CNT film to be used as an active sensing material in thin
      film temperature sensors.

PMID- 30241385
TI  - Data-Driven Approach to Improving the Risk Assessment Process of Medical
      Failures.
AB  - In recent decades, many researchers have focused on the issue of medical failures
      in the healthcare industry. A variety of techniques have been employed to assess
      the risk of medical failure and to generate strategies to reduce the frequency of
      medical failures. Considering the limitations of the traditional method-failure
      mode and effects analysis (FMEA)-for risk assessment and quality improvement,
      this paper presents two models developed using data envelopment analysis (DEA).
      One is called the slacks-based measure DEA (SBM-DEA) model, and the other is a
      novel data-driven approach (NDA) that combines FMEA and DEA. The relative
      advantages of the three models are compared. In this paper, an infant security
      case consisting of 16 failure modes at Western Wake Medical Center in Raleigh,
      North Carolina, U.S., was employed. The results indicate that both SBM-DEA and
      NDA may improve the discrimination and accuracy of detection compared to the
      traditional method of FMEA. However, NDA was found to have a relative advantage
      over SBM-DEA due to its risk assessment capability and precise detection of
      medical failures.

PMID- 30241388
TI  - Maximum Correntropy Based Unscented Particle Filter for Cooperative Navigation
      with Heavy-Tailed Measurement Noises.
AB  - In this paper, a novel robust particle filter is proposed to address the
      measurement outliers occurring in the multiple autonomous underwater vehicles
      (AUVs) based cooperative navigation (CN). As compared with the classic unscented
      particle filter (UPF) based on Gaussian assumption of measurement noise, the
      proposed robust particle filter based on the maximum correntropy criterion (MCC)
      exhibits better robustness against heavy-tailed measurement noises that are often
      induced by measurement outliers in CN systems. Furthermore, the proposed robust
      particle filter is computationally much more efficient than existing robust UPF
      due to the use of a Kullback-Leibler distance-resampling to adjust the number of
      particles online. Experimental results based on actual lake trial show that the
      proposed maximum correntropy based unscented particle filter (MCUPF) has better
      estimation accuracy than existing state-of-the-art robust filters for CN systems
      with heavy-tailed measurement noises, and the proposed MCUPF has lower
      computational complexity than existing robust particle filters.

PMID- 30241386
TI  - NADH Dehydrogenase Subunit-2 237 Leu/Met Polymorphism Influences the Association
      of Coffee Consumption with Serum Chloride Levels in Male Japanese Health Checkup
      Examinees: An Exploratory Cross-Sectional Analysis.
AB  - BACKGROUND: Nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit-2 237
      leucine/methionine (ND2-237 Leu/Met) polymorphism has been shown to modify the
      association of coffee consumption with the risk of hypertension, dyslipidemia,
      and abnormal glucose tolerance, and low serum chloride levels have been shown to
      be associated with all-cause and cardiovascular disease mortality. Therefore, the
      purpose of the present study was to investigate whether ND2-237 Leu/Met
      polymorphism influences the association of coffee consumption with serum chloride
      levels in male Japanese health checkup examinees. METHODS: From among individuals
      visiting the hospital for a regular medical checkup, 402 men (mean age +/-
      standard deviation, 53.9 +/- 7.8 years) were selected for inclusion in the study.
      After ND2-237 Leu/Met genotyping, we conducted an exploratory cross-sectional
      study to examine the combined association of ND2-237 Leu/Met polymorphism and
      coffee consumption with serum electrolyte levels. RESULTS: After adjusting for
      age, body mass index, habitual smoking, alcohol consumption, green tea
      consumption, and antihypertensive medication, coffee consumption significantly
      increased serum chloride levels (p for trend = 0.001) in men with the ND2-237Leu
      genotype. After these adjustments, the odds ratios (ORs) for low levels of serum
      chloride, defined as <100 mEq/L, were found to be dependent on coffee consumption
      (p for trend = 0.001). In addition, the OR for low levels of serum chloride was
      significantly lower in men with the ND2-237Leu genotype who consumed >=4 compared
      with <1 cup of coffee per day (OR = 0.096, 95% confidence interval = 0.010-0.934;
      p = 0.044). However, neither serum chloride levels nor risk of low levels of
      serum chloride appeared to be dependent on coffee consumption. CONCLUSIONS: The
      results suggest that ND2-237 Leu/Met polymorphism modifies the association of
      coffee consumption with serum chloride levels in middle-aged Japanese men.

PMID- 30241389
TI  - The Impact of Heat Stress and Water Deficit on the Photosynthetic and Stomatal
      Physiology of Olive (Olea europaea L.)-A Case Study of the 2017 Heat Wave.
AB  - Heat waves are predicted to increase in frequency and duration in many regions as
      global temperatures rise. These transient increases in temperature above normal
      average values will have pronounced impacts upon the photosynthetic and stomatal
      physiology of plants. During the summer of 2017, much of the Mediterranean
      experienced a severe heat wave. Here, we report photosynthetic leaf gas exchange
      and chlorophyll fluorescence parameters of olive (Olea europaea cv. Leccino)
      grown under water deficit and full irrigation over the course of the heat wave as
      midday temperatures rose over 40  degrees C in Central Italy. Heat stress induced
      a decline in the photosynthetic capacity of the olives consistent with reduced
      ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) activity. Damage to
      photosystem II was more apparent in plants subject to water deficit. In contrast
      to previous studies, higher temperatures induced reductions in stomatal
      conductance. Heat stress adversely affected the carbon efficiency of olive. The
      selection of olive varieties with enhanced tolerance to heat stress and/or
      strategies to mitigate the impact of higher temperatures will become increasingly
      important in developing sustainable agriculture in the Mediterranean as global
      temperatures rise.

PMID- 30241390
TI  - Philosophy and Application of High-Resolution Temperature Sensors for Stratified
      Waters.
AB  - Every application may have its specifically designed sensor. For studying the
      effects of short-term temperature variations on life in water, a high-resolution
      sensor has been designed with low noise level <0.1 mK. Pro and cons of the design
      include its adequacy for use in large heat-capacity environments like water but
      less in air. The sensor can be used under high static environmental pressure of
      >1000 Bar (>108 N m-2) in the deepest ocean regions. Its response time of 0.5 s
      in water allows quantitative studies of internal wave turbulent mixing effects,
      e.g., on the redistribution of matter and on nearly completely submerged human
      bodies. In a chain of >100 sensors, clocks are synchronized to sample within 0.02
      s and a verified range of 600 m.

PMID- 30241387
TI  - Molecular Genotyping (SSR) and Agronomic Phenotyping for Utilization of Durum
      Wheat (Triticum durum Desf.) Ex Situ Collection from Southern Italy: A Combined
      Approach Including Pedigreed Varieties.
AB  - In South Italy durum wheat (Triticum durum Desf.) has a long-time tradition of
      growing and breeding. Accessions collected and now preserved ex situ are a
      valuable genetic resource, but their effective use in agriculture and breeding
      programs remains very low. In this study, a small number (44) of simple sequence
      repeats (SSR) molecular markers were used to detect pattern of diversity for 136
      accessions collected in South Italy over time, to identify the genepool of
      origin, and establish similarities with 28 Italian varieties with known pedigree
      grown in Italy over the same time-period. Phenotyping was conducted for 12
      morphophysiological characters of agronomic interest. Based on discriminant
      analysis of principal components (DAPC) and STRUCTURE analysis six groups were
      identified, the assignment of varieties reflected the genetic basis and breeding
      strategies involved in their development. Some "old" varieties grown today are
      the result of evolution through natural hybridization and conservative pure line
      selection. A small number of molecular markers and little phenotyping coupled
      with powerful statistical analysis and comparison to pedigreed varieties can
      provide enough information on the genetic structure of durum wheat germplasm for
      a quick screening of the germplasm collection able to identify accessions for
      breeding or introduction in low input agriculture.

PMID- 30241391
TI  - New Constitutive Matrix in the 3D Cell Method to Obtain a Lorentz Electric Field
      in a Magnetic Brake.
AB  - In this work, we have obtained a new constitutive matrix to calculate the induced
      Lorentz electric current of in a conductive disk in movement within a magnetic
      field using the cell method in 3D. This disk and a permanent magnet act as a
      magnetic brake. The results obtained are compared with those obtained with the
      finite element method (FEM) using the computer applications Getdp and femm. The
      error observed is less than 0.1173%. Likewise, a second verification has been
      made in the laboratory using Hall sensors to measure the magnetic field in the
      proximity of the magnetic brake.

PMID- 30241392
TI  - The Role of PPARbeta/delta in Melanoma Metastasis.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor (PPAR) beta/delta, a
      ligand-activated transcription factor, is involved in diverse biological
      processes including cell proliferation, cell differentiation, inflammation and
      energy homeostasis. Besides its well-established roles in metabolic disorders,
      PPARbeta/delta has been linked to carcinogenesis and was reported to inhibit
      melanoma cell proliferation, anchorage-dependent clonogenicity and ectopic
      xenograft tumorigenicity. However, PPARbeta/delta's role in tumour progression
      and metastasis remains controversial. METHODS: In the present studies, the
      consequence of PPARbeta/delta inhibition either by global genetic deletion or by
      a specific PPARbeta/delta antagonist, 10h, on malignant transformation of
      melanoma cells and melanoma metastasis was examined using both in vitro and in
      vivo models. RESULTS: Our study showed that 10h promotes epithelial-mesenchymal
      transition (EMT), migration, adhesion, invasion and trans-endothelial migration
      of mouse melanoma B16/F10 cells. We further demonstrated an increased tumour cell
      extravasation in the lungs of wild-type mice subjected to 10h treatment and in
      Pparbeta/delta-/- mice in an experimental mouse model of blood-borne pulmonary
      metastasis by tail vein injection. This observation was further supported by an
      increased tumour burden in the lungs of Pparbeta/delta-/- mice as demonstrated in
      the same animal model. CONCLUSION: These results indicated a protective role of
      PPARbeta/delta in melanoma progression and metastasis.

PMID- 30241393
TI  - Highly Accurate Step Counting at Various Walking States Using Low-Cost Inertial
      Measurement Unit Support Indoor Positioning System.
AB  - Accurate step counting is essential for indoor positioning, health monitoring
      systems, and other indoor positioning services. There are several publications
      and commercial applications in step counting. Nevertheless, over-counting, under
      counting, and false walking problems are still encountered in these methods. In
      this paper, we propose to develop a highly accurate step counting method to solve
      these limitations by proposing four features: Minimal peak distance, minimal peak
      prominence, dynamic thresholding, and vibration elimination, and these features
      are adaptive with the user's states. Our proposed features are combined with
      periodicity and similarity features to solve false walking problem. The proposed
      method shows a significant improvement of 99.42% and 96.47% of the average of
      accuracy in free walking and false walking problems, respectively, on our
      datasets. Furthermore, our proposed method also achieves the average accuracy of
      97.04% on public datasets and better accuracy in comparison with three commercial
      step counting applications: Pedometer and Weight Loss Coach installed on Lenovo
      P780, Health apps in iPhone 5s (iOS 10.3.3), and S-health in Samsung Galaxy S5
      (Android 6.01).

PMID- 30241394
TI  - Sodium Citrate Increases Expression and Flux of Mg2+ Transport Carriers Mediated
      by Activation of MEK/ERK/c-Fos Pathway in Renal Tubular Epithelial Cells.
AB  - A chronic magnesium deficiency may be one of the causes of lifestyle-related
      diseases such as hypertension and diabetes. Serum Mg2+ concentration is strictly
      controlled by the reabsorption pathway in the renal tubules, but little is known
      about how Mg2+ reabsorption is upregulated. We searched for food compounds which
      can increase the expression levels of Mg2+ transport carriers including transient
      receptor potential melastatin 6 (TRPM6) channel and cyclin M2 (CNNM2). Sodium
      citrate (SC) increased the mRNA levels of TRPM6 and CNNM2 in renal tubular
      epithelial NRK-52E cells. The SC-induced elevation of TRPM6 was inhibited by
      U0126, a mitogen-activated protein kinase kinase (MEK) inhibitor, but the CNNM2
      was not. SC increased the levels of p-ERK1/2 and p-c-Fos, which were inhibited by
      U0126. SC induced alkalization of culture medium. Both SC and alkalization
      enhanced Mg2+ influx, which was inhibited by U0126 and introduction of TRPM6
      siRNA. The reporter activity of TRPM6 was increased by SC and alkalization, which
      was suppressed by mutation in an AP-1-binding site. The SC-induced elevation of p
      ERK1/2 and p-EGFR was inhibited by diphenylene iodonium, a nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase inhibitor, and erlotinib, an epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitor. SC did not change the
      level of acetyl histone H3, but increased the association of c-Fos with the
      promoter region of TRPM6. These results suggest that SC increases TRPM6
      expression and Mg2+ influx mediated by the activation of NADPH oxidase and an
      EGFR/ERK/c-Fos pathway in the renal tubules.

PMID- 30241397
TI  - Evolution of Pretreatment Assessment and Direct Acting Antiviral Regimens in
      Accordance with Upgrading Guidelines: A Retrospective Study in HIV/HCV Coinfected
      Patients.
AB  - Since the advent of new direct acting antivirals (DAA), substantial changes in
      hepatitis C (HCV) treatment guidelines have occurred. However, little is known
      about how these recommendations have been adopted into clinical practice. We
      conducted a retrospective review of human immunodeficiency virus (HIV)/HCV
      coinfected patients treated with DAAs at the Ryan White Clinic of the Jackson
      Health System in Miami, FL, USA. Our aim was to determine changes in HCV
      evaluation and treatment patterns in the use of DAAs over a four-year period from
      January 2014 to December 2017. Data were divided into two periods: period 1 (2014
      2015) and period 2 (2016-2017). In comparison with the rest of the cohort,
      patients in period 2 had a lower frequency of advanced liver disease (24.4% vs.
      48.6%, p = 0.026) and underwent more elastography (34.1% vs. 2.7%, p < 0.001) and
      less ultrasound (78.0% vs. 97.3%, p = 0.011). They were more often treated with
      ledipasvir/sofosbuvir (85.4% vs. 56.8%, p = 0.005) and less often with
      simeprevir/sofosbuvir (0% vs. 32.4%, p < 0.001). Gastrointestinal side effects
      were reported less frequently (2.4% vs. 18.9%, p = 0.017) in this period. In
      accordance with the updated guidelines, our study demonstrated a growing
      preference for non-invasive methods to assess fibrosis in recent years. Regarding
      treatment, there was a clear preference for second generation DAAs in 2016-2017,
      along with initiation of treatment in the early stages of liver disease.

PMID- 30241396
TI  - A Field Procedure for the Assessment of the Centring Uncertainty of Geodetic and
      Surveying Instruments.
AB  - The uncertainty evaluation of survey measurements is a daily and essential task
      in any surveying work. The result of a measurement is, in fact, only complete
      when accompanied by a statement of its uncertainty. Miscentring, or centring
      error, is one of the sources of uncertainty in every basic survey measurement
      which may have a great effect on horizontal angle measurement for short
      distances. In the literature, different terms and values are considered to refer
      to this source of uncertainty. Standard ISO 17123 provides different procedures
      for assessing the measurement uncertainty of geodetic and surveying instruments,
      with the aim of checking their suitability for the intending and immediate task
      in field conditions. ISO 17123 is aware of the importance of uncertainty in the
      instrument centring, but it does not propose any standardised procedure for its
      assessment. In this study, we propose such a procedure following a Type A
      evaluation (through the statistical analysis of series of observations), avoiding
      using values from Type B evaluations (from manufacturer's specifications,
      handbooks, personal experiences, etc.) that could be unsuitable for the
      conditions of the task. Uncertainty can be individualised for a particular
      instrument (which includes the plummet type), ground mark, operator, and other
      factors on which the results could be dependent. The testing methodology includes
      a configuration of the test field, measurements, and calculation, following the
      structure of each part of the standard ISO 17123. An experimental application is
      included with two different total stations, which also includes a statistical
      analysis of the results.

PMID- 30241398
TI  - Miniature Uncooled and Unchopped Fiber Optic Infrared Thermometer for Application
      to Cutting Tool Temperature Measurement.
AB  - A new infrared thermometer, sensitive to wavelengths between 3 MUm and 3.5 MUm,
      has been developed. It is based on an Indium Arsenide Antimony (InAsSb)
      photodiode, a transimpedance amplifier, and a sapphire fiber optic cable. The
      thermometer used an uncooled photodiode sensor and received infrared radiation
      that did not undergo any form of optical chopping, thereby, minimizing the
      physical size of the device and affording its attachment to a milling machine
      tool holder. The thermometer is intended for applications requiring that the
      electronics are located remotely from high-temperature conditions incurred during
      machining but also affording the potential for use in other harsh conditions.
      Other example applications include: processes involving chemical reactions and
      abrasion or fluids that would otherwise present problems for invasive contact
      sensors to achieve reliable and accurate measurements. The prototype thermometer
      was capable of measuring temperatures between 200  degrees C and 1000  degrees C
      with sapphire fiber optic cable coupling to high temperature conditions. Future
      versions of the device will afford temperature measurements on a milling machine
      cutting tool and could substitute for the standard method of embedding
      thermocouple wires into the cutting tool inserts. Similarly, other objects within
      harsh conditions could be measured using these techniques and accelerate
      developments of the thermometer to suit particular applications.

PMID- 30241399
TI  - Degradation Studies Realized on Natural Rubber and Plasticized Potato Starch
      Based Eco-Composites Obtained by Peroxide Cross-Linking.
AB  - The obtaining and characterization of some environmental-friendly composites that
      are based on natural rubber and plasticized starch, as filler, are presented.
      These were obtained by peroxide cross-linking in the presence of a polyfunctional
      monomer used here as cross-linking co-agent, trimethylolpropane trimethacrylate.
      The influence of plasticized starch amount on the composites physical and
      mechanical characteristics, gel fraction and cross-link density, water uptake,
      structure and morphology before and after accelerated (thermal) degradation, and
      natural (for one year in temperate climate) ageing, was studied. Differences of
      two orders of magnitude between the degradation/aging methods were registered in
      the case of some mechanical characteristics, by increasing the plasticized starch
      amount. The cross-link density, water uptake and mass loss were also significant
      affected by the plasticized starch amount increasing and exposing for one year to
      natural ageing in temperate climate. Based on the results of Fourier Transform
      Infrared Spectroscopy (FTIR) and cross-link density measurements, reaction
      mechanisms attributed to degradation induced by accelerated and natural ageing
      were done. SEM micrographs have confirmed in addition that by incorporating a
      quantity of hydrophilic starch amount over 20 phr and by exposing the composites
      to natural ageing, and then degradability can be enhanced by comparing with
      thermal degradation.

PMID- 30241401
TI  - New Insight into the Chloroacetanilide Herbicide Degradation Mechanism through a
      Nucleophilic Attack of Hydrogen Sulfide.
AB  - The nucleophilic attack of hydrogen sulfide (HS-) on six different
      chloroacetanilide herbicides was evaluated theoretically using the dispersion
      corrected hybrid functional wB97XD and the 6-311++G(2d,2p) Pople basis sets. The
      six evaluated substrates were propachlor (A), alachlor (B), metolachlor (C),
      tioacetanilide (D), beta-anilide (E), and methylene (F). Three possible
      mechanisms were considered: (a) bimolecular nucleophilic substitution (SN2)
      reaction mechanism, (b) oxygen assistance, and (c) nitrogen assistance.
      Mechanisms based on O- and N-assistance were discarded due to a very high
      activation barrier in comparison with the corresponding SN2 mechanism, with the
      exception of compound F. The N-assistance mechanism for compound F had a free
      activation energy of 23.52 kcal/mol, which was close to the value for the
      corresponding SN2 mechanism (23.94 kcal/mol), as these two mechanisms could occur
      in parallel reactions with almost 50% of each one. In compounds A to D, an
      important electron-withdrawing effect of the C=O and C=S groups was seen, and
      consequently, the activation free energies in these SN2 reactions were smaller,
      with a value of approximately 18 kcal/mol. Instead, compounds E and F, which have
      a CH2 group in the beta-position, presented a higher activation free energy (~22
      kcal/mol). Good agreement was found between experimental and theoretical values
      for all cases, and a reaction force analysis was performed on the intrinsic
      reaction coordinate profile in order to gain more details about the reaction
      mechanism. Finally, from the natural bond orbital (NBO) analysis, it was possible
      to evaluate the electronic reorganization through the reaction pathway where all
      the transition states were early in nature in the reaction coordinate (deltaBav <
      50%); the transition states corresponding to compounds A to D turned out to be
      more synchronous than those for compounds E and F.

PMID- 30241400
TI  - Metformin: An Old Drug with New Applications.
AB  - Metformin is a biguanide drug that has been used to treat type 2 diabetes
      mellitus for more than 60 years. The United Kingdom Prospective Diabetic Study
      (UKPDS) has shown metformin to improve mortality rates in diabetes patients, and
      recent studies suggest metformin has additional effects in treating cancer,
      obesity, nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome
      (PCOS), and metabolic syndrome. Metformin has also been shown to alleviate weight
      gain associated with antipsychotic medication. Metformin has recently been
      extensively studied and emerging evidence suggests metformin decreases hepatocyte
      triglyceride accumulation in NAFLD and prevents liver tumorigenesis.
      Interestingly, studies have also shown metformin reduces visceral fat, suppresses
      white-adipose-tissue (WAT) extracellular matrix remodeling, and inhibits obesity
      induced inflammation. However, clinical evidence for using metformin to treat
      NAFLD, cancer, metabolic syndrome, or to prevent hepatocellular carcinoma in
      NAFLD patients is lacking. This review therefore addresses the potential
      beneficial effects of metformin on NAFLD, its role in protecting against cardiac
      ischemia-reperfusion (I/R) injury, atherosclerosis, glucotoxicity, and
      lipotoxicity induced oxidative and ER stress in pancreatic beta-cell dysfunction,
      as well as its underlying molecular mechanisms of action.

PMID- 30241395
TI  - The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices
      as Accomplices.
AB  - BACKGROUND: The functional interplay between tumor cells and their adjacent
      stroma has been suggested to play crucial roles in the initiation and progression
      of tumors and the effectiveness of chemotherapy. The extracellular matrix (ECM),
      a complex network of extracellular proteins, provides both physical and chemicals
      cues necessary for cell proliferation, survival, and migration. Understanding how
      ECM composition and biomechanical properties affect cancer progression and
      response to chemotherapeutic drugs is vital to the development of targeted
      treatments. METHODS: 3D cell-derived-ECMs and esophageal cancer cell lines were
      used as a model to investigate the effect of ECM proteins on esophageal cancer
      cell lines response to chemotherapeutics. Immunohistochemical and qRT-PCR
      evaluation of ECM proteins and integrin gene expression was done on clinical
      esophageal squamous cell carcinoma biopsies. Esophageal cancer cell lines (WHCO1,
      WHCO5, WHCO6, KYSE180, KYSE 450 and KYSE 520) were cultured on decellularised
      ECMs (fibroblasts-derived ECM; cancer cell-derived ECM; combinatorial-ECM) and
      treated with 0.1% Dimethyl sulfoxide (DMSO), 4.2 uM cisplatin, 3.5 uM 5
      fluorouracil and 2.5 uM epirubicin for 24 h. Cell proliferation, cell cycle
      progression, colony formation, apoptosis, migration and activation of signaling
      pathways were used as our study endpoints. RESULTS: The expression of collagens,
      fibronectin and laminins was significantly increased in esophageal squamous cell
      carcinomas (ESCC) tumor samples compared to the corresponding normal tissue.
      Decellularised ECMs abrogated the effect of drugs on cancer cell cycling,
      proliferation and reduced drug induced apoptosis by 20-60% that of those plated
      on plastic. The mitogen-activated protein kinase-extracellular signal-regulated
      kinase (MEK-ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K/Akt)
      signaling pathways were upregulated in the presence of the ECMs. Furthermore, our
      data show that concomitant addition of chemotherapeutic drugs and the use of
      collagen- and fibronectin-deficient ECMs through siRNA inhibition synergistically
      increased cancer cell sensitivity to drugs by 30-50%, and reduced colony
      formation and cancer cell migration. CONCLUSION: Our study shows that ECM
      proteins play a key role in the response of cancer cells to chemotherapy and
      suggest that targeting ECM proteins can be an effective therapeutic strategy
      against chemoresistant tumors.

PMID- 30241402
TI  - Chromaticity-Tunable and Thermal Stable Phosphor-in-Glass Inorganic Color
      Converter for High Power Warm w-LEDs.
AB  - In this work, an aluminate silicate garnet phosphor, Y2Mg2Al2Si2O12:Ce3+
      (YMASG:Ce3+), exhibiting strong and broad yellow-orange emission, was
      successfully synthesized. Attributed to the double cation substitution of
      YAG:Ce3+, which led to a compression effect, a redshift was observed with respect
      to YAG:Ce3+. More importantly, a transparent phosphor-in-glass (PiG) sample was
      obtained by incorporating the phosphor YMASG:Ce3+ into a special low-melting
      precursor glass. The energy dispersive spectrometer (EDS) mapping analysis of the
      as-prepared PiG sample indicates that YMASG:Ce3+ was successfully incorporated
      into the glass host, and its powders were uniformly distributed in glass. The
      photoluminescence intensity of the PiG sample was higher than that of the powder
      due to its relatively high thermal conductivity. Additionally, the combination of
      the PiG sample and a blue high-power chip generated a modular white LED with a
      luminous efficacy of 54.5 lm/W, a correlated color temperature (CCT) of 5274 K,
      and a color rendering index (CRI) of 79.5 at 350 mA.

PMID- 30241403
TI  - Hepatoprotective Effect of Ugonin M, A Helminthostachyszeylanica Constituent, on
      Acetaminophen-Induced Acute Liver Injury in Mice.
AB  - The present study aimed to discover the possible effectiveness of Ugonin M, a
      unique flavonoid isolated from Helminthostachys zeylanica-a traditional Chinese
      medicine used as anti-inflammatory medicine-and to elucidate the potential
      mechanisms of Ugonin M in the acute liver injury induced by acetaminophen (APAP).
      In this study, Ugonin M significantly ameliorated APAP-induced histopathological
      changes and the typical liver function biomarkers (i.e., alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), and total bilirubin (T-Bil)). It also
      affected APAP-induced abnormal lipid metabolism including total cholesterol (TC)
      and triglyceride (TG) in the serum. In inflammatory pharmacological action,
      Ugonin M suppressed the pro-inflammatory mediators such as nitric oxide (NO) and
      the lipid peroxidation indicator malondialdehyde (MDA). In addition, Ugonin M
      reinforced hemeoxygenase-1 (HO-1) protein expression and the production of
      antioxidant enzymes viz superoxide dismutase (SOD), glutathione peroxidase (GPx),
      and catalase (CAT). Furthermore, inflammation-associated cytokines including
      tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta as
      well as proteins such as inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) were decreased by the pretreatment of Ugonin M.
      Moreover, this study found that pretreatment of Ugonin M apparently decreased
      nuclear factor-kappa B (NF-kappaB) and mitogen-activated protein kinases (MAPKs)
      activation via inhibition of the degradation of NF-kappaB, inhibitory kappaB
      alpha (IkappaB-alpha), extracellular regulated kinase (ERK), c-Jun-N-terminal
      (JNK), and p38 active phosphorylation. In conclusion, Ugonin M significantly
      showed a protective effect against APAP-induced liver injury by reducing
      oxidative stress and inflammation. Thus, Ugonin M could be one of the effective
      components of H. zeylanica that plays a major role in the treatment of
      inflammatory disorders.

PMID- 30241404
TI  - Composite Hierarchical Anti-Disturbance Control with Multisensor Fusion for
      Compact Optoelectronic Platforms.
AB  - In the aerospace field, compact optoelectronic platforms (COPs) are being
      increasingly equipped on unmanned aircraft systems (UAS). They assist UAS in a
      range of mission-specific tasks such as disaster relief, crop testing, and
      firefighting. However, the strict constraint of structure space makes COPs
      subject to multi-source disturbances. The application of a low-cost and low
      precision sensor also affects the system control performance. A composite
      hierarchical anti-disturbance control (CHADC) scheme with multisensor fusion is
      explored herein to improve the motion performance of COPs in the presence of
      internal and external disturbances. Composite disturbance modelling combining the
      characteristic of wire-wound moment is presented in the inner layer. The adaptive
      mutation differential evolution algorithm is implemented to identify and optimise
      the model parameters of the system internal disturbance. Inverse model
      compensation and finite-time nonlinear disturbance observer are then constructed
      to compensate for multiple disturbances. A non-singular terminal sliding mode
      controller is constructed to attenuate disturbance in the outer layer. A
      stability analysis for both the composite disturbance compensator and the closed
      loop system is provided using Lyapunov stability arguments. The phase lag-free
      low-pass filter is implemented to interfuse multiple sensors with different order
      information and achieve satisfactory noise suppression without phase lag.
      Experimental results demonstrate that the proposed CHADC strategy with a higher
      quality signal has an improved performance for multi-source disturbance
      compensation.

PMID- 30241405
TI  - Development of Organic-Inorganic Hybrid Optical Gas Sensors for the Non-Invasive
      Monitoring of Pathogenic Bacteria.
AB  - Hybrid optical gas sensors, based on different organic and inorganic materials,
      are proposed in this paper, with the aim of using them as optical artificial nose
      systems. Three types of organic and inorganic dyes, namely zinc-porphyrin,
      manganese-porphyrin, and zinc-phthalocyanine, were used as gas sensing materials
      to fabricate a thin-film coating on glass substrates. The performance of the gas
      sensor was enhanced by a thermal treatment process. The optical absorption
      spectra and morphological structure of the sensing films were confirmed by UV-Vis
      spectrophotometer and atomic force microscope, respectively. The optical gas
      sensors were tested with various volatile compounds, such as acetic acid,
      acetone, ammonia, ethanol, ethyl acetate, and formaldehyde, which are commonly
      found to be released during the growth of bacteria. These sensors were used to
      detect and discriminate between the bacterial odors of three pathogenic species
      (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) grown in
      Luria-Bertani medium. Based on a pattern recognition (PARC) technique, we showed
      that the proposed hybrid optical gas sensors can discriminate among the three
      pathogenic bacterial odors and that the volatile organic compound (VOC) odor
      pattern of each bacterium was dependent on the phase of bacterial growth.

PMID- 30241406
TI  - Effect of Arbuscular Mycorrhizal Fungi on Pratylenchus penetrans Infestation in
      Apple Seedlings under Greenhouse Conditions.
AB  - A major problem in fruit cultivation in Flanders is replant disease due to a lack
      of uncultivated soils available for new plantings. Replant disease can cause poor
      growth and affect time to full production, however Arbuscular Mycorrhizal Fungi
      (AMF) can prove their usefulness with regard to these problems. To further
      investigate the effect of AMF on nematodes, different AMF species were amended to
      potted apple seedlings in the presence of the nematode Pratylenchus penetrans.
      Generally, apple seedlings grew better in the presence of nematodes when
      mycorrhiza were inoculated into the soil. Moreover, a positive correlation (R2 >=
      0.88) was found between the percentage root length colonization of the roots of
      apple seedlings, by AMF species, and nematode reduction in the soil of the
      seedlings. Indigenous AMF could colonize the roots of apple seedlings the most
      efficiently, resulting in a higher biocontrol effect. Besides, a synergistic
      effect was observed when two AMF strains were applied together leading to a
      significant growth response of the seedlings.

PMID- 30241408
TI  - Avocado Seed: A Comparative Study of Antioxidant Content and Capacity in
      Protecting Oil Models from Oxidation.
AB  - Increasingly, consumers want products containing little or no synthetic
      compounds. Avocado seeds, which are a residue of the food industry, could be used
      to obtain extracts with high antioxidant power. In the present study, the most
      popular radical scavenging methods are presented, establishing a comparison
      between them, besides working with two different extractions: pure methanol and
      ethanol-water (50:50 v/v). The radical scavenging assay methods ORAC and ABTS
      were performed, as well as a novel method: the reaction to methoxy radical, as
      determined by electron paramagnetic resonance (EPR). Peroxide value and
      thiobarbituric acid reactive compounds (TBARs) were used to monitor the oxidation
      of avocado seed oil, as well as the power of the avocado seed extract (ASE) to
      delay oil oxidation by oxidation induction time (OIT) and measured by
      differential scanning calorimetry (DSC). Radical scavenging methods have values
      between 1310-263 umol TE/g of mass dissolved for ORAC and ABTS, respectively. The
      individual contribution of each of the compounds present in the extract was
      analyzed. The sum of all of them contributed up to 84% of the total radical
      scavenging activity. The concentration of 0.75% ASE causes a delay in the
      oxidation that is close to 80%, as measured by OIT. This implies that avocado
      seed residue may have a use as a natural antioxidant source, providing added
      value to organic waste.

PMID- 30241407
TI  - Review of the Clinical Experiences of Feeding Infants Formula Containing the
      Human Milk Oligosaccharide 2'-Fucosyllactose.
AB  - Human milk oligosaccharides (HMOs) are the third most abundant solid component in
      human milk after lactose and lipids. Preclinical research has demonstrated that
      HMOs and specifically 2'-fucosyllactose (2'-FL) are more than a prebiotic and
      have multiple functions, including immune, gut, and cognition benefits.
      Previously, human milk has been the only source for significant levels of HMOs.
      The most abundant HMO in most mothers' breast milk is 2'-FL. Recently, 2'-FL has
      been synthesized and shown to be structurally identical to the 2'-FL found in
      human milk. 2'-FL HMO is now available in some commercial infant formulas. The
      purpose of this narrative review was to summarize the clinical experiences of
      feeding infant formula supplemented with the HMO, 2'-FL. Most of these studies
      investigated standard intact milk protein-based infant formulas containing 2'-FL,
      and one evaluated a partially hydrolyzed whey-based formula. Collectively, these
      clinical experiences demonstrated that 2'-FL being added to infant formula was
      safe, well-tolerated, and absorbed and excreted with similar efficiency to 2'-FL
      in human milk. Further, infants that were fed formula with 2'-FL had immune
      benefits, fewer parent-reported respiratory infections, and improved symptoms of
      formula intolerance. Ultimately, infant formula with 2'-FL supports immune and
      gut health and is closer compositionally and functionally to human milk.

PMID- 30241409
TI  - Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition
      of Bronchoalveolar Fluid and Lung Tissue in Cardiac Surgery Patients.
AB  - Pulmonary dysfunction is among the most frequent complications to cardiac
      surgeries. Exposure of blood to the cardiopulmonary bypass (CPB) circuit with
      subsequent lung ischemia-reperfusion leads to the production of inflammatory
      mediators and increases in microvascular permeability. The study aimed to
      elucidate histological, cellular, and metabolite changes following two lung
      protective regimens during CPB with Histidine-Tryptophan-Ketoglutarate (HTK)
      enriched or warm oxygenated blood pulmonary perfusion compared to standard
      regimen with no pulmonary perfusion. A total of 90 patients undergoing CPB were
      randomized to receiving HTK, oxygenated blood or standard regimen. Of these,
      bronchoalveolar lavage fluid (BALF) and lung tissue biopsies were obtained before
      and after CPB from 47 and 25 patients, respectively. Histopathological scores,
      BALF cell counts and metabolite screening were assessed. Multivariate and
      univariate analyses were performed. Profound histological, cellular, and
      metabolic changes were identified in all patients after CPB. Histological and
      cellular changes were similar in the three groups; however, some metabolite
      profiles were different in the HTK patients. While all patients presented an
      increase in inflammatory cells, metabolic acidosis, protease activity and
      oxidative stress, HTK patients seemed to be protected against severe acidosis,
      excessive fatty acid oxidation, and inflammation during ischemia-reperfusion.
      Additional studies are needed to confirm these findings.

PMID- 30241410
TI  - Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and
      Summer Seasonality of HCoV-HKU1.
AB  - Human coronaviruses (HCoVs) cause mild to severe respiratory diseases. Six types
      of HCoVs have been discovered, the most recent one termed the Middle East
      respiratory syndrome coronavirus (MERS-CoV). The aim of this study is to monitor
      the circulation of HCoV types in the population during 2015-2016 in Israel. HCoVs
      were detected by real-time PCR analysis in 1910 respiratory samples, collected
      from influenza-like illness (ILI) patients during the winter sentinel influenza
      survey across Israel. Moreover, 195 HCoV-positive samples from hospitalized
      patients were detected during one year at Soroka University Medical Center. While
      no MERS-CoV infections were detected, 10.36% of patients in the survey were
      infected with HCoV-OC43 (43.43%), HCoV-NL63 (44.95%), and HCoV-229E (11.62%)
      viruses. The HCoVs were shown to co-circulate with respiratory syncytial virus
      (RSV) and to appear prior to influenza virus infections. HCoV clinical symptoms
      were more severe than those of RSV infections but milder than influenza symptoms.
      Hospitalized patients had similar HCoV types percentages. However, while it was
      absent from the public winter survey, 22.6% of the patients were HCoV-HKU1
      positives, mainly during the spring-summer period.

PMID- 30241411
TI  - Cell-Type-Specific Modulation of Hydrogen Peroxide Cytotoxicity and 4
      Hydroxynonenal Binding to Human Cellular Proteins In Vitro by Antioxidant Aloe
      vera Extract.
AB  - Although Aloe vera contains numerous bioactive components, the activity
      principles of widely used A. vera extracts are uncertain. Therefore, we analyzed
      the effects of genuine A. vera aqueous extract (AV) on human cells with respect
      to the effects of hydrogen peroxide (H2O2) and 4-hydroxynonenal (HNE). Fully
      developed A. vera leaves were harvested and analyzed for vitamin C, carotenoids,
      total soluble phenolic content, and antioxidant capacity. Furthermore, human
      cervical cancer (HeLa), human microvascular endothelial cells (HMEC), human
      keratinocytes (HaCat), and human osteosarcoma (HOS) cell cultures were treated
      with AV extract for one hour after treatment with H2O2 or HNE. The cell number
      and viability were determined using Trypan Blue, and endogenous reactive oxygen
      species (ROS) production was determined by fluorescence, while intracellular HNE
      protein adducts were measured for the first time ever by genuine cell-based HNE
      His ELISA. The AV extract expressed strong antioxidant capacities (1.1 mmol of
      Trolox eq/g fresh weight) and cell-type-specific influence on the cytotoxicity of
      H2O2, as well as on endogenous production of ROS and HNE-protein adducts induced
      by HNE treatment, while AV itself did not induce production of ROS or HNE-protein
      adducts at all. This study, for the first time, revealed the importance of HNE
      for the activity principles of AV. Since HMEC cells were the most sensitive to
      AV, the effects of AV on microvascular endothelia could be of particular
      importance for the activity principles of Aloe vera extracts.

PMID- 30241412
TI  - Specialized Pro-Resolving Lipid Mediators in Cystic Fibrosis.
AB  - In cystic fibrosis (CF), impaired airway surface hydration (ASL) and mucociliary
      clearance that promote chronic bacterial colonization, persistent inflammation,
      and progressive structural damage to the airway wall architecture are typically
      explained by ion transport abnormalities related to the mutation of the gene
      coding for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
      channel. However, the progressive and unrelenting inflammation of the CF airway
      begins early in life, becomes persistent, and is excessive relative to the
      bacterial burden. Intrinsic abnormalities of the inflammatory response in cystic
      fibrosis have been suggested but the mechanisms involved remain poorly
      understood. This review aims to give an overview of the recent advances in the
      understanding of the defective resolution of inflammation in CF including the
      abnormal production of specialized pro-resolving lipid mediators (lipoxin and
      resolvin) and their impact on the pathogenesis of the CF airway disease.

PMID- 30241413
TI  - Facile Three-Component Synthesis, Insecticidal and Antifungal Evaluation of Novel
      Dihydropyridine Derivatives.
AB  - In an attempt to find the neonicotinoid insecticides, twenty novel
      dihydropyridine derivatives were designed, "green" synthesized via one pot facile
      three-component reaction and evaluated for their bioactivities against
      Tetranychus cinnabarinus, Myzus persicae, Brevicoryne brassicae, Fusarium
      oxysporum f. sp. vasinfectum, Magnaporthe oryzae, Sclerotinia sclerotiorum and
      Botrytis cinereal. All of the tested compounds showed potent insecticidal
      activity, and some were much better in comparison with imidacloprid (IMI).
      Especially, compounds 3d (LC50: 0.011 mM) and 5c (LC50: 0.025 mM) were 12.2- and
      5.4-fold more active than IMI (LC50: 0.135 mM) against T. cinnabarinus,
      respectively. Moreover, out of all the derivatives, compound 3d (LC50: 0.0015 mM)
      exhibited the strongest insecticidal activity against B. brassicae and compound
      3i (LC50: 0.0007 mM) displayed the strongest insecticidal activity against M.
      persicae. Surprisingly, when the concentration of compound 4 was 50 mg/L, the
      inhibition rate against F. oxysporum and S. sclerotiorum reached 45.00% and
      65.83%, respectively. The present work indicated that novel dihydropyridine
      derivatives could be used as potential lead compounds for developing
      neonicotinoid insecticides and agricultural fungicides.

PMID- 30241414
TI  - Correlations between Phytohormones and Drought Tolerance in Selected Brassica
      Crops: Chinese Cabbage, White Cabbage and Kale.
AB  - Drought is one of the major abiotic stresses affecting the productivity of
      Brassica crops. To understand the role of phytohormones in drought tolerance, we
      subjected Chinese cabbage (B. rapa ssp. pekinensis), white cabbage (B. oleracea
      var. capitata), and kale (B. oleracea var. acephala) to drought and examined the
      stress response on the physiological, biochemical and hormonal levels. The
      phytohormones abscisic acid (ABA), auxin indole-3-acetic acid (IAA),
      brassinosteroids (BRs), cytokinins (CKs), jasmonates (JAs), and salicylic acid
      (SA) were analyzed by ultra-high-performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS). Based on the physiological and biochemical markers
      the Chinese cabbage exhibited the lowest tolerance, followed by the white
      cabbage, while the kale appeared to be the most tolerant to drought. The drought
      tolerance of the kale correlated with increased levels of SA, ABA, IAA, CKs iP(R)
      and cZ(R), and typhasterol (TY), a precursor of active BRs. In contrast, the
      drought sensitivity of the Chinese cabbage correlated with a significant increase
      in ABA, JAs and the active BRs castasterol (CS) and brassinolide (BL). The
      moderately tolerant white cabbage, positioned between the kale and Chinese
      cabbage, showed more similarity in terms of the phytohormone patterns with the
      kale. We concluded that the drought tolerance in Brassicaceae is mostly
      determined by the increased endogenous levels of IAA, CKs, ABA and SA and the
      decreased levels of active BRs.

PMID- 30241415
TI  - Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R
      Mutation in Locally Advanced Papillary Thyroid Cancer.
AB  - Locally advanced thyroid cancer exhibits aggressive clinical features requiring
      extensive neck dissection. Therefore, it is important to identify changes in the
      tumor biology before local progression. Here, whole exome sequencing (WES) using
      tissues from locally advanced papillary thyroid cancer (PTC) presented a large
      number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN),
      but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a
      novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth
      analysis for exome sequencing data from the primary tumor presented altered
      nucleotide 'A' at a very low frequency indicating intra-tumor heterogeneity
      between the primary tumor and MLN. Computational prediction models such as
      PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and
      stability. In vitro, HHIP G516R increased cell proliferation and promoted cell
      migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a
      representative example for the intra-tumor heterogeneity of locally advanced
      thyroid cancer, which can be a potential future therapeutic target for this
      disease.

PMID- 30241416
TI  - Gamma Irradiation-Assisted Synthesis of Cellulose Nanocrystal-Reinforced Gelatin
      Hydrogels.
AB  - Herein, we describe the use of gamma irradiation to prepare hydrogels comprising
      alpha-cellulose and cellulose nanocrystal (CNC)-reinforced gelatin in the absence
      of crosslinking agents. In this study, cellulose was extracted from rice husks by
      an alkali and bleaching treatment followed by acid hydrolysis to produce CNC. A
      semi-interpenetrating network (semi-IPN) of hydrogels was developed by the
      miscibility between gelatin and cellulosic materials. Compared to those prepared
      from alpha-cellulose, hydrogels prepared by dispersion of CNCs exhibited
      remarkably enhanced stiffness and swelling properties, which was ascribed to the
      uniform distribution of CNCs and their increased crystallinity. Improved pore
      structure, arrangement, and rigidity of CNC-reinforced gelatin hydrogels, which
      induced the swelling mechanism resulting in higher and faster water uptake was
      observed with a scanning electron microscope (SEM), compared to cellulose
      reinforced gelatin hydrogels. Moreover, in vitro drug profiling demonstrated that
      CNC/gelatin hydrogels exhibit good drug loading/release behavior and are thus
      suitable for use in drug-delivery applications.

PMID- 30241418
TI  - An Innovative Method for Forming Balls by Cross Rolling.
AB  - The paper describes an innovative cross rolling method that enables the
      production of six balls at the same time, each ball with a diameter of 100 mm.
      The principle of the proposed rolling technique is discussed and the tools used
      in this forming process are described. Two variations of the proposed method for
      producing balls were investigated, one performed with the use of flat tools and
      the other with the use of two rolls. Results of the numerical modelling are
      discussed. They clearly demonstrate that the proposed method can be used to
      produce balls with large diameters. Rolling experiments were performed under
      laboratory conditions to produce 40 mm diameter balls, i.e., in the 1:2.5 scale.
      The experimental findings show a good qualitative agreement with the numerical
      results.

PMID- 30241417
TI  - Perfluorooctanoic Acid (PFOA) Exposure in Early Life Increases Risk of Childhood
      Adiposity: A Meta-Analysis of Prospective Cohort Studies.
AB  - Some articles have examined perfluorooctanoic acid (PFOA) exposure in early life
      in relation to risk of childhood adiposity. Nevertheless, the results from
      epidemiological studies exploring the associations remain inconsistent and
      contradictory. We thus conducted an analysis of data currently available to
      examine the association between PFOA exposure in early life and risk of childhood
      adiposity. The PubMed, EMBASE, and Web of Science databases were searched to
      identify studies that examined the impact of PFOA exposure in early life on
      childhood adiposity. A random-effects meta-analysis model was used to pool the
      statistical estimates. We identified ten prospective cohort studies comprising
      6076 participants with PFOA exposure. The overall effect size (relative risk or
      odds ratio) for childhood overweight was 1.25 (95% confidence interval (CI):
      1.04, 1.50; I2 = 40.5%). In addition, exposure to PFOA in early life increased
      the z-score of childhood body mass index (beta = 0.10, 95% CI: 0.03, 0.17; I2 =
      27.9%). Accordingly, exposure to PFOA in early life is associated with an
      increased risk for childhood adiposity. Further research is needed to verify
      these findings and to shed light on the molecular mechanism of PFOA in adiposity.

PMID- 30241419
TI  - Orosensory Detection of Dietary Fatty Acids Is Altered in CB1R-/- Mice.
AB  - Obesity is one of the major public health issues, and its prevalence is steadily
      increasing all the world over. The endocannabinoid system (ECS) has been shown to
      be involved in the intake of palatable food via activation of cannabinoid 1
      receptor (CB1R). However, the involvement of lingual CB1R in the orosensory
      perception of dietary fatty acids has never been investigated. In the present
      study, behavioral tests on CB1R-/- and wild type (WT) mice showed that the
      invalidation of Cb1r gene was associated with low preference for solutions
      containing rapeseed oil or a long-chain fatty acid (LCFA), such as linoleic acid
      (LA). Administration of rimonabant, a CB1R inverse agonist, in mice also brought
      about a low preference for dietary fat. No difference in CD36 and GPR120 protein
      expressions were observed in taste bud cells (TBC) from WT and CB1R-/- mice.
      However, LCFA induced a higher increase in [Ca2+]i in TBC from WT mice than that
      in TBC from CB1R-/- mice. TBC from CB1R-/- mice also exhibited decreased
      Proglucagon and Glp-1r mRNA and a low GLP-1 basal level. We report that CB1R is
      involved in fat taste perception via calcium signaling and GLP-1 secretion.

PMID- 30241421
TI  - Academic Career Progression of Chinese-Origin Pharmacy Faculty Members in Western
      Countries.
AB  - Background: The field of Pharmacy education is experiencing a paucity of
      underrepresented minorities (URMs) faculty worldwide. The aim of this study is to
      investigate the current professional status of Chinese-origin pharmacy faculty
      members, who are considered as a good model of URMs at pharmacy academia in
      western countries, and identify the influencing factors to their academic career
      progression in academic careers. Methods: An online questionnaire was sent to
      Chinese-origin academic staffs at pharmacy schools in US, UK, Canada, Australia,
      and New Zealand. The survey comprised demographic information, educational
      background, and the influencing factors to academic career progression. Results:
      The vast majority of Chinese faculty members who worked in US were male.
      Individuals with junior academic title comprised the largest proportion. Over 75%
      of Chinese-origin pharmacy academics were involved in scientific disciplines
      (e.g., pharmaceutics, pharmacology, and medicinal chemistry). Usually, Chinese
      origin academic members spent 4 years obtaining their first academic jobs after
      finishing PhD degree, and need 5-6 years to get academic promotion. The
      contributing factors of academic promotion were high quality publications and
      external funding. Conclusion: Our research offers a deep insight into academic
      career progression for URMs and give some valuable advice for their pharmacy
      academic paths.

PMID- 30241420
TI  - Oxidative Alteration of Trp-214 and Lys-199 in Human Serum Albumin Increases
      Binding Affinity with Phenylbutazone: A Combined Experimental and Computational
      Investigation.
AB  - Human serum albumin (HSA) is a target for reactive oxygen species (ROS), and
      alterations of its physiological functions caused by oxidation is a current
      issue. In this work, the amino-acid residues Trp-214 and Lys-199, which are
      located at site I of HSA, were experimentally and computationally oxidized, and
      the effect on the binding constant with phenylbutazone was measured. HSA was
      submitted to two mild oxidizing reagents, taurine monochloramine (Tau-NHCl) and
      taurine dibromamine (Tau-NBr2). The oxidation of Trp-214 provoked spectroscopic
      alterations in the protein which were consistent with the formation of N'
      formylkynurenine. It was found that the oxidation of HSA by Tau-NBr2, but not by
      Tau-NHCl, provoked a significant increase in the association constant with
      phenylbutazone. The alterations of Trp-214 and Lys-199 were modeled and simulated
      by changing these residues using the putative oxidation products. Based on the
      Amber score function, the interaction energy was measured, and it showed that,
      while native HSA presented an interaction energy of -21.3 kJ/mol, HSA with Trp
      214 altered to N'-formylkynurenine resulted in an energy of -28.4 kJ/mol, and HSA
      with Lys-199 altered to its carbonylated form resulted in an energy of -33.9
      kJ/mol. In summary, these experimental and theoretical findings show that
      oxidative alterations of amino-acid residues at site I of HSA affect its binding
      efficacy.

PMID- 30241422
TI  - Structural, Luminescent and Thermal Properties of Heteronuclear PdII-LnIII-PdII
      Complexes of Hexadentate N2O4 Schiff Base Ligand.
AB  - New PdII-LnIII-PdII complexes of hexadentate N2O4 Schiff base ligand (H4L: N,N'
      bis(2,3-dihydroxybenzylidene)-1,3-diamino-2,2-dimethylpropane) with Eu (1), Tb
      (2), Er (3) and Yb (4) ([Pd2Eu(H2L)2NO3](NO3)2?2H2O?2CH3OH 1,
      [Pd2Ln(H2L)2H2O](NO3)3?3H2O, where Ln = Tb 2, Er 3, [Pd2Yb(H2L)2H2O](NO3)3?5.5H2O
      4) were synthesized and characterized structurally and physicochemically by
      thermogravimetry (TG), differential thermogravimetry (DTG), differential scanning
      calorimetry (DSC) and luminescence measurements. The compounds 1-4 are built of
      cationic heterometallic PdII-LnIII-PdII trinuclear units. The palladium(II)
      centers adopt a planar square geometry occupying the smaller N2O2 cavity of the
      Schiff base ligand. The lanthanide(III) is surrounded by two Schiff base ligands
      (eight oxygen atoms) and its coordination sphere is supplemented by a chelating
      bidentate nitrate ion in 1 or by a water molecule in 2-4. The complexes have a
      bent conformation along the PdII-LnIII-PdII line with valence angles in the
      ranges of 162-171 degrees . The decomposition process of the complexes results in
      mixtures of: PdO, Pd and respective lanthanide oxides Eu2O3, Tb2O3, Tb4O7, Er2O3,
      Yb2O3. The luminescent measurements show low efficiency intramolecular energy
      transfer only in the complex of terbium(III) (2).

PMID- 30241424
TI  - Sucrosomial(r) Iron Supplementation in Mice: Effects on Blood Parameters,
      Hepcidin, and Inflammation.
AB  - Sucrosomial(r) Iron is a recently developed formulation to treat iron deficiency
      based on ferric pyrophosphate covered by a matrix of phospholipids plus sucrose
      esters of fatty acids. Previous data indicated that Sucrosomial(r) Iron is
      efficiently absorbed by iron-deficient subjects, even at low dosage, and without
      side effects. Its structural properties may suggest that it is absorbed by an
      intestinal pathway which is different to the one used by ionic iron. Although,
      studies in vitro showed that Sucrosomial(r) Iron is readily absorbed, no animal
      models have been established to study this important aspect. To this aim, we
      induced iron deficient anemia in mice by feeding them with a low-iron diet, and
      then we treated them with either Sucrosomial(r) Iron or sulfate iron by gavage
      for up to two weeks. Both iron formulations corrected anemia and restored iron
      stores in a two-week period, but with different kinetics. Ferrous Sulfate was
      more efficient during the first week and Sucrosomial(r) Iron in the second week.
      Of note, when given at the same concentrations, Ferrous Sulfate induced the
      expression of hepcidin and four different inflammatory markers (Socs3, Saa1, IL6
      and CRP), while Sucrosomial(r) Iron did not. We conclude that anemic mice are
      interesting models to study the absorption of oral iron, and that Sucrosomial(r)
      Iron is to be preferred over Ferrous Sulfate because of similar absorption but
      without inducing an inflammatory response.

PMID- 30241423
TI  - Pospiviroid Infection of Tomato Regulates the Expression of Genes Involved in
      Flower and Fruit Development.
AB  - Viroids are unencapsidated, single-stranded, covalently-closed circular, highly
      structured, noncoding RNAs of 239-401 nucleotides that cause disease in several
      economically important crop plants. In tomato (Solanum lycopersicum cv. Rutgers),
      symptoms of pospiviroid infection include stunting, reduced vigor, flower
      abortion, and reduced size and number of fruits, resulting in significant crop
      losses. Dramatic alterations in plant development triggered by viroid infection
      are the result of differential gene expression; in our study, we focused on the
      effect of tomato planta macho viroid (TPMVd) and Mexican papita viroid (MPVd)
      infection on gene networks associated with the regulation of flower and fruit
      development. The expression of several of the genes were previously reported to
      be affected by viroid infection, but two genes not previously studied were
      included. Changes in gene expression of SlBIGPETAL1 (bHLH transcription factor)
      and SlOVA6 (proline-like tRNA synthetase) are involved in petal morphology and
      fertility, respectively. Expression of SlOVA6 was down-regulated in flowers of
      TPMVd- and MPVd-infected plants, while expression of SlBIGPETAL1 was up-regulated
      in flowers. Up-regulation of SlBIGPETAL1 and down-regulation of SlOVA6 were
      positively correlated with symptoms such as reduced petal size and flower
      abortion. Expression analysis of additional tomato genes and a prediction of a
      global network association of genes involved in flower and fruit development and
      impacted by viroid infection may further elucidate the pathways underlying viroid
      pathogenicity.

PMID- 30241425
TI  - The Influence of Polymers on the Supersaturation Potential of Poor and Good Glass
      Formers.
AB  - The increasing number of poorly water-soluble drug candidates in pharmaceutical
      development is a major challenge. Enabling techniques such as amorphization of
      the crystalline drug can result in supersaturation with respect to the
      thermodynamically most stable form of the drug, thereby possibly increasing its
      bioavailability after oral administration. The ease with which such crystalline
      drugs can be amorphized is known as their glass forming ability (GFA) and is
      commonly described by the critical cooling rate. In this study, the
      supersaturation potential, i.e., the maximum apparent degree of supersaturation,
      of poor and good glass formers is investigated in the absence or presence of
      either hypromellose acetate succinate L-grade (HPMCAS-L) or vinylpyrrolidine
      vinyl acetate copolymer (PVPVA64) in fasted state simulated intestinal fluid
      (FaSSIF). The GFA of cinnarizine, itraconazole, ketoconazole, naproxen,
      phenytoin, and probenecid was determined by melt quenching the crystalline drugs
      to determine their respective critical cooling rate. The inherent supersaturation
      potential of the drugs in FaSSIF was determined by a solvent shift method where
      the respective drugs were dissolved in dimethyl sulfoxide and then added to
      FaSSIF. This study showed that the poor glass formers naproxen, phenytoin, and
      probenecid could not supersaturate on their own, however for some drug:polymer
      combinations of naproxen and phenytoin, supersaturation of the drug was enabled
      by the polymer. In contrast, all of the good glass formers-cinnarizine,
      itraconazole, and ketoconazole-could supersaturate on their own. Furthermore, the
      maximum achievable concentration of the good glass formers was unaffected by the
      presence of a polymer.

PMID- 30241429
TI  - Comparative fine structural studies of planulae and primary polyps of identical
      age of the sea pen, Ptilosarcus gurneyl.
AB  - Electron microscopic study of an 18-day-old planulae and primary polyps of the
      sea pen, Ptilosarcus gurneyi, reveals 14 cell types: sustentacular cell A,
      sustentacular cell B, nerve cell, sensory cell, cnidoblast, interstitial cell,
      five types of gland cell (A, B, C, D and E), amoebocyte, style cell and
      endodermal cell. Of these, 9 are found in the planula, 12 in polyps and 7 are
      common to both stages. The fine structure of all cell types is described. Since
      the planulae and polyps in this study were identical in age of development, the
      gaining and losing of certain types of cells in the polyp are attributed to
      changes associated with settlement and metamorphosis. Modifications of the seven
      common cell types during metamorphosis can also be attributed to the change of
      life style from pelagic to benthic.

PMID- 30241428
TI  - Comparative study of the stomatogastric system of several decapod crustacea. I.
      Skeleton.
AB  - The skeletal structure of the stomachs of several decapod Crustacea is described
      in detail. The general organization of the ossicles is similar for all species
      and the homologies of the elements can be recognized despite large variations
      from group to group. The Reptantia are characterized by a complex ossicle
      organization while the Natantia, on the other hand, are characterized by a simple
      organization. The various types of ossicle organization found in the decapod
      stomach can be arranged in a series ranging from simple to complex. The Brachyura
      have the most complex ossicle system and the Penaeidea the most simplified. This
      graded series of complexity closely follows the evolution of the Decapoda.

PMID- 30241430
TI  - A scanning electron microscopic study of differentiation of the digital pad in
      regenerating digits of the kenyan reed frog, Hyperolius viridiflavus ferniquei.
AB  - Newly metamorphosed Kenyan reed frogs, Hyperolius viridiflavus ferniquei, are
      able to regenerate amputated digits. The terminal digital pad is also completely
      reformed. Differentiation of the regenerating digital pad was studied by scanning
      electron microscopy. External differentiation of the digital pad began late in
      the second postamputational week with the appearance of small patches of
      specialized epidermal cells on the ventral surface of the regenerating digit. The
      differentiation of the pad spread out radially until late in the fourth week,
      when its overall shape approximated that of the normal digital pad. The
      appearance of patches of digital pad epidermis on the ends of spike regenerates
      arising from the forearm was also confirmed.

PMID- 30241427
TI  - Investigating Functional Roles for Positive Feedback and Cellular Heterogeneity
      in the Type I Interferon Response to Viral Infection.
AB  - Secretion of type I interferons (IFN) by infected cells mediates protection
      against many viruses, but prolonged or excessive type I IFN secretion can lead to
      immune pathology. A proper type I IFN response must therefore maintain a balance
      between protection and excessive IFN secretion. It has been widely noted that the
      type I IFN response is driven by positive feedback and is heterogeneous, with
      only a fraction of infected cells upregulating IFN expression even in clonal cell
      lines, but the functional roles of feedback and heterogeneity in balancing
      protection and excessive IFN secretion are not clear. To investigate the
      functional roles for feedback and heterogeneity, we constructed a mathematical
      model coupling IFN and viral dynamics that extends existing mathematical models
      by accounting for feedback and heterogeneity. We fit our model to five existing
      datasets, reflecting different experimental systems. Fitting across datasets
      allowed us to compare the IFN response across the systems and suggested different
      signatures of feedback and heterogeneity in the different systems. Further,
      through numerical experiments, we generated hypotheses of functional roles for
      IFN feedback and heterogeneity consistent with our mathematical model. We
      hypothesize an inherent tradeoff in the IFN response: a positive feedback loop
      prevents excessive IFN secretion, but also makes the IFN response vulnerable to
      viral antagonism. We hypothesize that cellular heterogeneity of the IFN response
      functions to protect the feedback loop from viral antagonism. Verification of our
      hypotheses will require further experimental studies. Our work provides a basis
      for analyzing the type I IFN response across systems.

PMID- 30241431
TI  - Blood circulation in the balanomorph barnacle, Megabalanus californicus
      (Pilsbry).
AB  - Compared to the lepadomorph barnacles, the morphology of hemolymph circulation in
      the balanomorphs is poorly known. This report on Megabalanus californicus is the
      first detailed description of blood circulation in a balanomorph barnacle. In
      Megabalanus hemolymph circulates in a similar pattern to that seen in
      lepadomorphs. However, Megabalanus shows major differences. (1) The mantle and
      associated structures ( =peduncle in the lepadomorphs) shows no large sinuses and
      blood is directed to branchiae via well defined vessels. (2) The gut is entirely
      invested with vessels from the distributive system (except for the proctodaeum).
      (3) A large sinus in the thoracic region (thoracic sinus) has no similar
      structure in the lepadomorphs. (4) The prosomal sinus is reduced and positioned
      dorsally. (5) The rostral sinus is larger than any found in the lepadomorphs and
      receives a substantial amount of blood from the peripheral circulation. The
      smallness of the prosomal sinus in Megabalanus probably is due to lack of a
      contractile peduncle. In the lepadomorphs the prosomal sinus likely serves as a
      storage sinus for hemolymph when the peduncle is contracted.

PMID- 30241426
TI  - Effect of A Very Low-Calorie Ketogenic Diet on Food and Alcohol Cravings,
      Physical and Sexual Activity, Sleep Disturbances, and Quality of Life in Obese
      Patients.
AB  - Psychological well-being and hunger and food control are two relevant factors
      involved in the success of weight-loss therapy in treating obesity. Thus, this
      study aims to evaluate food and alcohol cravings, physical and sexual activity,
      sleep, and life quality (QoL) in obese patients following a very low-calorie
      ketogenic (VLCK) diet, as well as the role of weight lost and ketosis on these
      parameters. A battery of psychological test was performed in twenty obese
      patients (12 females, 47.2 +/- 10.2 year and BMI of 35.5 +/- 4.4) through the
      course of a 4-month VLCK diet on four subsequent visits: baseline, maximum
      ketosis, reduced ketosis, and endpoint. Each subject acted as their own control.
      Relevantly, the dietary-induced changes in body composition (7.7 units of BMI
      lost, 18 kg of fat mass (1.2 kg of visceral fat mass)) were associated with a
      statistically significant improvement in food craving scores, physical activity,
      sleepiness, and female sexual function. Overall, these results also translated in
      a notable enhancement in QoL of the treated obese patients. Therefore, the rapid
      and sustained weight and fat mass (FM) loss induced by the VLCK diet is
      associated with good food control and improvements in the psychological well
      being parameters in obese subjects, which could contribute to the long-term
      success of this therapy.

PMID- 30241432
TI  - An unusual cytoplasmic organelle in oocytes of Ilyanassa obsoleta.
AB  - An unusual organelle in the oocytes of the marine mud snail Ilyanassa obsoleta is
      described and called a polymerosome, because of its several components.
      Polymerosomes appear at the beginning of vitellogenesis and persist, in part,
      through postvitellogenesis. The persistent part is similar to an organelle that
      has been described by other workers in the vegetal region and the polar lobe of
      the Ilyanassa egg.

PMID- 30241433
TI  - Anatomy and histology of the alimentary tract of the desert millipede Orthoporus
      ornatus (Girard) (Diplopoda: Spirostreptidae).
AB  - The alimentary tract of the desert millipede Orthoporus ornatus is essentially a
      straight tube consisting of a histologically distinct foregut, midgut, pylorus,
      hindgut, and rectum. Common to each region, but often different in regional
      appearance, are an outer sheath layer, longitudinal and circular muscle layers, a
      basement membrane, and an inner epithelial layer. Foregut and midgut lumina are
      lined by a cuticular intima, while a peritrophic membrane occurs in the midgut
      lumen. Gut structure is considered in the context of the known feeding habits and
      digestive efficiency of this long-lived, seasonally restricted detritivore.

PMID- 30241434
TI  - Comparative study of the stomatogastric system of the decapod crustacea. II.
      Musculature.
AB  - The stomach musculature of several species of decapod Crustacea is described in
      detail. All species are sufficiently similar so that muscle homologies can be
      established. The Natantia have a simplified muscle system while the Reptantia are
      characterized by a more complex muscle system. Species can be arranged in a
      graded series of muscle system complexity which closely follows the evolution of
      the decapod Crustacea. The information presented here should provide the basis
      for consistent identification of the stomatogastric motor neurons throughout the
      decapod Crustacea.

PMID- 30241435
TI  - Banding pattern and fibrillogenesis of ceratotrichia in shark fins.
AB  - Study by light microscopy, scanning electron microscopy and transmission electron
      microscopy of the distribution, structure and growth of ceratotrichia in the
      anterodorsal fin of a lemon shark, Negaprion brevirostris, and in the tailfin of
      a nurse shark, Ginglymostoma cirratum, shows that the ceratotrichia are large
      collagen fibers which develop in bilateral rows within the dermis. Surrounding
      each ceratotrichium is a layer of peritrichial fibroblasts containing secretory
      vesicles, which appear to be the source of matrix constituents. The peritrichial
      matrix contains bundles of fine, unbanded collagen fibrils as well as larger,
      banded fibrils like those in the matrix of ordinary connective tissue. The
      structure of the peritrichial fibroblasts and of the subjacent peritrichial
      matrix is the same as that of the fibroblasts and matrix of the conventional
      connective tissue throughout the fin dermis. Ceratotrichia grow by apposition of
      collagen fibrils from the peritrichial matrix. In cross section the ceratotrichia
      appear layered, evidently because of close packing of constituent fibrils in
      lamellae. In longitudinal section the ceratotrichia exhibit the conventional a,
      b, c, d and e bands of collagen. The e bands of show two distinct subbands, and
      the b bands three subbands. Periodicity of the banding pattern is approximately
      640 A like that of conventional collagen fibrils.

PMID- 30241436
TI  - A scanning electron microscopic study of the sacculus and lagena in the ears of
      fifteen species of teleost fishes.
AB  - The ulstrastructure of the saccular and lagenar maculae were studied in 15
      species of teleost fishes, using the scanning electron microscope. Particular
      attention was paid to hair cell orientation patterns, composition of the ciliary
      bundles on the hair cells, hair cell distributions, and supporting cell types.
      The hair cells on both otolithic organs are divided into several groups with all
      of the hair cells in each group oriented in the same direction. The posterior
      region of the saccular macula in all species had dorsally oriented hair cells on
      the dorsal half of the macula and ventrally oriented hair cells on the ventral
      half. The cells on the anterior end of the macula were oriented anteriorly and
      posteriorly, with the posterior group, in most species, being on the dorsal half
      of the anterior region of the macula. There was considerable inter-specific
      variation upon this basic pattern. Inter-specific variation on the lagenar macula
      was considerably less than on the saccular macula. The basic pattern in all of
      the species includes one dorsal cell group and one ventral cell group. There are
      four more-or-less discrete ciliary bundles, each varying in the relative size of
      the kinocilia and stereocilia. Intermediary forms were also observed, making it
      difficult to differentiate ciliary bundles in some instances. It was apparent,
      however, that several of the ciliary bundles were found in particular macular
      regions.

PMID- 30241437
TI  - In-Gap States and Band-Like Transport in Memristive Devices.
AB  - Point defects such as oxygen vacancies cause emergent phenomena such as resistive
      switching in transition-metal oxides, but their influence on the electron
      transport properties is far from being understood. Here, we employ direct mapping
      of the electronic structure of a memristive device by spectromicroscopy. We find
      that oxygen vacancies result in in-gap states that we use as input for single
      band transport simulations. Because the in-gap states are situated below the
      Fermi level, they do not contribute to the current directly but impact the shape
      of the conduction band. Accordingly, we can describe our devices with band-like
      transport and tunneling across the Schottky barrier at the interface.

PMID- 30241438
TI  - Thermopower and Unconventional Nernst Effect in the Predicted Type-II Weyl
      Semimetal WTe2.
AB  - WTe2 is one of a series of recently discovered high mobility semimetals, some of
      whose properties are characteristic of topological Dirac or Weyl metals. One of
      its most interesting properties is the unsaturated giant magnetoresistance that
      it exhibits at low temperatures. An important question is the degree to which
      this property can be ascribed to a conventional semimetallic model in which a
      highly compensated, high mobility metal exhibits large magnetoresistance. Here,
      we show that the longitudinal thermopower (Seebeck effect) of semimetallic WTe2
      exfoliated flakes exhibits periodic sign changes about zero with increasing
      magnetic field that indicates distinct electron and hole Landau levels and nearly
      fully compensated electron and hole carrier densities. However, inconsistent with
      a conventional semimetallic picture, we find a rapid enhancement of the Nernst
      effect at low temperatures that is nonlinear in magnetic field, which is
      consistent with Weyl points in proximity to the Fermi energy. Hence, we
      demonstrate the role played by the Weyl character of WTe2 in its transport
      properties.

PMID- 30241439
TI  - Nanostructured biomedical selenium at the biological interface (Review).
AB  - This paper critically reviews the current evidence of research in biomedical
      applications of selenium nanoparticles (SeNPs) and their effects at cellular and
      tissue levels. In recent years, interest in SeNPs as a natural trace element
      nanomaterial for nanomedicine has resulted in a number of studies evaluating
      their bioactivities, such as anticancer, antimicrobial, and antioxidant
      properties. Significant data have been generated to demonstrate the effectiveness
      of SeNPs alone or in combination with other reagents. Their activities are
      demonstrated through in vitro and in vivo experimentation; yet, the levels of
      efficacy need to be improved, particularly when compared with those of
      pharmaceutical drugs (such as antibiotics and cytotoxic chemotherapeutic drugs).
      However, promising evidence suggests decreased toxicity when using SeNPs, and
      more importantly their ability to perform as an interfacing biomaterial with
      cells and tissues. SeNPs have demonstrated unique antibacterial properties: they
      inhibit bacterial adhesion, growth, and/or quorum sensing and as a result prevent
      biofilm formation on medical devices, to name a few. Therefore, as with other
      nanomaterials, SeNPs warrant further study as part of the biomaterial-based
      therapeutic toolkit as an alternative to traditional pharmaceutical agents. This
      paper will provide a succinct review of recent studies on SeNPs to critically
      assess the findings in the light of effectiveness, particularly highlighting the
      roles of the cellular interface. Finally, an outlook of the potential of SeNPs
      will be presented to highlight the need for more intensive studies of material
      stability, mechanistic understanding at subcellular levels, and investigations
      into their combinational and/or synergistic effects with other bioactive reagents
      including pharmaceutical drugs.

PMID- 30241440
TI  - A qualitative study on alcohol consumption and HIV treatment adherence among men
      living with HIV in Ugandan fishing communities.
AB  - Ugandan fishing communities are dually burdened with high rates of HIV and
      alcohol use. This qualitative study explores context and motivation of alcohol
      consumption, and alcohol's effect on antiretroviral treatment (ART) adherence,
      among male fisherfolk living with HIV in Wakiso District, Uganda. We conducted in
      depth semi-structured interviews with 30 men in HIV care and on ART, and used a
      thematic analysis approach for analysis. Alcohol use was identified as a major
      barrier to ART adherence through cognitive impairment and the intentional
      skipping of doses when drinking. Men reportedly reduced their drinking since HIV
      diagnosis - motivated by counseling received from providers and a newfound desire
      to live a healthy lifestyle. However, social, occupational, and stress-related
      influences that make alcohol reduction difficult were identified. Our findings
      suggest alcohol use may pose a challenge to ART adherence for fishermen living
      with HIV - and has implications for the tailoring of screening and brief
      intervention for alcohol reduction in HIV care for this population.

PMID- 30241441
TI  - Determination of 226Ra, 232Th and 40K in teeth by use of gamma spectroscopy.
AB  - This study entails the measurement of the specific activity of natural
      radionuclides (226Ra, 40K and 232Th) in 18 tooth samples obtained from the clinic
      of the Universiti Sains Malaysia (USM), Penang, by using an HPGe detector. The
      specific activity of 226Ra, 40K and 232Th was measured to estimate the hazard
      index of the radionuclides, radium equivalent activities (Raeq), external,
      internal hazard indices (Hex, Hin), and absorbed dose (Dout, Din). The maximum
      values of concentration of 226Ra, 232Th and 40K in the tooth samples were found
      to be 60.82, 60.29 and 594.22 Bq kg-1, respectively. Maximum values of Raeq, Hex,
      Hin, Dout and Din were found to be 192.78 Bq kg-1, 0.520, 0.685, 89.29 and 169.81
      nGy h-1, Igamma and Ialpha as 0.702 and 0.304, respectively. The results were
      lower than the average world value (UNSCEAR). In addition, a strong correlation
      was found between the concentrations of 226Ra and Raeq, between energy and net
      area, as well as between radionuclides (226Ra, 40K and 232Th) in tooth samples
      and age of volunteers. This study showed that the concentrations and hazard
      indices of tooth samples are below the recommended safe levels; therefore, the
      study area is considered safe in terms of radiological health hazards.

PMID- 30241442
TI  - TWEAK and monocyte to HDL ratio as a predictor of metabolic syndrome in patients
      with polycystic ovary syndrome.
AB  - We aimed at analyzing serum TWEAK levels and monocyte/HDL ratio in polycystic
      ovary syndrome (PCOS) and their predictivity for metabolic syndrome (MS) in PCOS.
      We included 71 women with PCOS and 40 healthy controls without any cardiovascular
      risk factors in this cross-sectional study. Patient group was classified as MS
      positive (n = 34) and negative (n = 37). Study group had higher monocyte/HDL
      ratio and TWEAK levels (9.59 +/- 2.82 vs 8.2 +/- 2.46, p = .007 and 1085.54 +/-
      780.95 vs 694.88 +/- 369.67 ng/ml, p = .009). Monocyte/HDL ratio and TWEAK levels
      were higher in MS positive group (10.47 +/- 2.81 vs 8.77 +/- 2.61, p = .01 and
      1417.59 +/- 921.52 vs 780.41 +/- 455.67, p = .009). In multivariate regression
      analysis, monocyte/HDL ratio (>9.9, OR 3.42, 95%CI 1.41-5.78, p = .008) and TWEAK
      (>846.5 ng/ml, OR 5.49, 95%CI 3.14-7.59, p = .002) were found to be independent
      predictors of MS in study group. Discriminative value of monocyte/HDL ratio for
      MS in study group was evaluated by receiver operating curve. Area under curve for
      monocyte/HDL ratio was 0.669 with a sensitivity of 70.3% and specifity of 67.7%,
      cutoff value was >9.9. Receiver operating curve for TWEAK at >846.5 pg/ml
      threshold to diagnose MS in study group was performed and area under the curve
      was 0.769 with a sensitivity of 73% and specifity of 72%. TWEAK and monocyte/HDL
      ratio may be promising in predicting MS at early stages in PCOS to prevent future
      cardiovascular diseases by modifying life-style or giving pharmacotheraphy.

PMID- 30241443
TI  - Mental health in South African adolescents living with HIV: correlates of
      internalising and externalising symptoms.
AB  - Although declining in all other age groups, AIDS-related deaths among adolescents
      are increasing. In the context of HIV, mental health problems are associated with
      negative health outcomes, including non-adherence to life-saving ART. For
      effective programming it is essential to identify factors associated with
      psychological outcomes in this population. Adopting a socioecological
      perspective, we aimed to identify correlates of internalising and externalising
      symptoms in a large, representative sample of South African adolescents living
      with HIV. HIV-positive adolescents (n = 1060), who received care in public health
      facilities in South Africa's Eastern Cape, completed measures of internalising
      and externalising symptoms. Hypothesised correlates included HIV and health
      related factors (physical health, mode of infection, medication side-effects,
      disclosure, stigma), health-service related factors (negative interactions with
      clinic staff, clinic support group), interpersonal factors (abuse, bullying
      victimisation, social support), parenting-related factors (orphanhood, positive
      parenting, parental monitoring, parent communication), as well as individual and
      demographic-related factors (self-efficacy, age, gender, urban/rural location,
      poverty). Correlates operating across a variety of contexts were identified.
      Bullying victimisation, self-efficacy, and positive parenting may be particularly
      salient intervention targets as they were associated with better outcomes on most
      or all mental health measures, can be addressed without directly targeting
      adolescents living with HIV (reducing the chances of accidental exposure and
      stigma), and are associated with better adolescent mental health in South Africa
      more generally.

PMID- 30241445
TI  - Do day-3 embryo grade predict day-5 blastocyst transfer outcomes in patients with
      good prognosis?
AB  - The main aim was to investigate whether or not day-3 embryo grade could predict
      day-5 blastocyst transfer outcomes in patients with good prognosis. This study
      included 233 elective single blastocyst transfers (eSBT) by D5 selection with
      conventional morphology (CM) and 121 elective single blastocyst transfers (eSBT)
      by D5 selection with time-lapse monitoring system (TL) from October 2016 to
      October 2017. All the patients were submitted to controlled ovarian stimulation
      (COS) with long-term protocol and transferred for the first time. The main
      outcome measures were clinical pregnancy rates (CPR) and ongoing pregnancy (OPR).
      Our results suggested that CPR (58.04 versus 57.89 versus 55.56%; p = .957) and
      OPR (66.07 versus 65.79 versus 64.44%; p = .981) were comparable among day 3
      grades I, grades II, and grades III groups. We also observed that the TL group
      showed a slightly better CPR and OPR than CM group (p > .05). Our findings
      suggested that good or poor embryos at day-3 were not predictive of the outcomes
      of good-quality blastocysts in a good-prognosis population. It needed to be
      emphasized that time-lapse monitoring might be useful for elective single
      blastocyst transfer.

PMID- 30241444
TI  - Artificial Pancreas Systems for People With Type 2 Diabetes: Conception and
      Design of the European CLOSE Project.
AB  - In the last 10 years tremendous progress has been made in the development of
      artificial pancreas (AP) systems for people with type 1 diabetes (T1D). The pan
      European consortium CLOSE (Automated Glu cose Contro l at H ome for People with
      Chronic Disea se) is aiming to develop integrated AP solutions (APplus) tailored
      to the needs of people with type 2 diabetes (T2D). APplus comprises a product and
      service package complementing the AP system by obligatory training as well as
      home visits and telemedical consultations on demand. Outcome predictors and
      performance indicators shall help to identify people who could benefit most from
      AP usage and facilitate the measurement of AP impact in diabetes care. In a first
      step CLOSE will establish a scalable APplus model case working at the interface
      between patients, homecare service providers, and payers in France. CLOSE will
      then scale up APplus by pursuing geographic distribution, targeting additional
      audiences, and enhancing AP functionalities and interconnectedness. By being part
      of the European Institute of Innovation and Technology (EIT) Health public
      private partnership, CLOSE is committed to the EIT "knowledge triangle" pursuing
      the integrated advancement of technology, education, and business creation.
      Putting stakeholders, education, and impact into the center of APplus advancement
      is considered key for achieving wide AP use in T2D care.

PMID- 30241446
TI  - Enhanced gene transfection efficiency by low-dose 25 kDa polyethylenimine by the
      assistance of 1.8 kDa polyethylenimine.
AB  - Gene therapy is a promising strategy for treatments of various diseases.
      Efficient and safe introduction of therapeutic genes into targeted cells is
      essential to realize functions of the genes. High-molecular-weight
      polyethylenimines (HMW PEIs) including 25 kDa branched PEI and 22 kDa linear PEI
      are widely used for in vitro gene transfection. However, high-gene transfection
      efficiency is usually accompanied with high cytotoxicity, which hampers their
      further clinical study. On the contrary, low-molecular-weight polyethylenimines
      (LMW PEIs) such as 1.8 kDa PEI and 800 Da PEI show good biocompatibility but
      their applications are limited by the poor DNA condensation capability. In this
      study, we find that 1.8 kDa PEI, but not 800 Da PEI combined with low-dose 25 kDa
      PEI could significantly promote gene transfection with low cytotoxicity. Plasmids
      encoding enhanced green fluorescence protein (EGFP) were delivered by the
      combined PEI and gene transfection efficiency was evaluated by microscopic
      observation and flow cytometry. Parameters including concentrations of 25 kDa PEI
      and 1.8 kDa PEI and preparation ways were further optimized. This study presents
      an efficient and safe combined PEI-based non-viral gene delivery strategy with
      potential for in vivo applications.

PMID- 30241447
TI  - Prostate cancer risk assessment in men with an initial P.S.A. below 3 ng/mL:
      results from the Goteborg randomized population-based prostate cancer screening
      trial.
AB  - OBJECTIVE: To evaluate the long-term outcome of men with an initial prostate
      specific antigen (PSA) level below 3 ng/mL and whether the free-to-total (F/T
      PSA) ratio is a useful prognostic marker in this range. MATERIALS AND METHODS:
      This study is based on 5,174 men aged 50-66 years, who in 1995-1996 participated
      in the first round of the Goteborg randomized screening trial (initial T-PSA
      level <3 ng/mL). These men were subsequently invited biennially for PSA and F/T
      PSA screening until they reached the upper age limit (on average 69 years).
      Biopsy was recommended if PSA >= 3 ng/mL. RESULTS: After a median follow-up of
      18.9 years, 754 men (14.6%) were diagnosed with prostate cancer (PC). The overall
      cumulative PC incidence was 17.2%. It increased from 7.9% among men with T-PSA of
      <=0.99 ng/mL to 26.0% in men with T-PSA levels of 1-1.99 ng/mL and 40.3% in men
      between 2-2.99 ng/mL (p < 0.001). The initial PSA was also related to the
      incidence of Gleason >=7 PC (3.7% vs 9.7% vs 10.9%) and PC death (0.3% vs 1.1% vs
      1.5%). Adding F/T PSA did not improve PC prediction in terms of Harrell
      concordance index (base model 0.76 vs 0.76) nor improvement of the likelihood of
      the model (p = 0.371). CONCLUSIONS: Some men with initial PSA < 3 ng/mL will be
      diagnosed too late, despite participating in an organized screening program,
      indicating that prompt diagnosis is justified in these men. PC incidence and risk
      of PC death was associated with PSA., but F/T PSA had no predictive value.

PMID- 30241448
TI  - Exploring single-domain antibody thermostability by molecular dynamics
      simulation.
AB  - Single-domain antibodies also known as nanobodies are recombinant antigen-binding
      domains that correspond to the heavy-chain variable region of camelid antibodies.
      Previous experimental studies showed that the nanobodies have stable and active
      structures at high temperatures. In this study, the thermal stability and
      dynamics of nanobodies have been studied by employing molecular dynamics
      simulation at different temperatures. Variations in root mean square deviation,
      native contacts, and solvent-accessible surface area of the nanobodies during the
      simulation were calculated to analyze the effect of different temperatures on the
      overall conformation of the nanobody. Then, the thermostability mechanism of this
      protein was studied through calculation of dynamic cross-correlation matrix,
      principal component analyses, native contact analyses, and root mean square
      fluctuation. Our results manifest that the side chain conformation of some
      residues in the complementarity-determining region 3 (CDR3) and also the
      interaction between alpha-helix region of CDR3 and framework2 play a critical
      role to stabilize the protein at a high temperature. Communicated by Ramaswamy H.
      Sarma.

PMID- 30241449
TI  - Visualizing phosphatidylcholine via mass spectrometry imaging: relevance to human
      health.
AB  - INTRODUCTION: Mass spectrometry imaging (MSI) techniques are nowadays widely used
      to obtain spatially resolved metabolite information from biological tissues.
      Since (phospho)lipids occur in all animal tissues and are very sensitively
      detectable, they are often in the focus of such studies. This particularly
      applies for phosphatidylcholines (PC) which are very sensitively detectable as
      positive ions due to the permanent positive charge of their choline headgroup.
      Areas covered: After a short introduction of lipid species occurring in
      biological systems and approaches normally used to obtain spatially resolved mass
      spectra (with the focus on matrix-assisted laser desorption/ionization coupled to
      time-of-flight (MALDI-TOF) MSI) a survey will be given which diseases have so far
      been characterized by changes of the PC composition. Expert commentary: Since PC
      species are very sensitively detectable by MS, sensitivity is not a major issue.
      However, spatial resolution is still limited and cellular dimensions can be
      hardly resolved by MALDI-TOF MSI, which is a critical point of the available
      approaches. Due to lacks of reproducibility and standardization further
      development is required.

PMID- 30241450
TI  - Therapeutic targets for inflammation-mediated airway remodeling in chronic lung
      disease.
AB  - INTRODUCTION: Acute exacerbations of chronic lung disease account for substantial
      morbidity and health costs. Repeated inflammatory episodes and attendant
      bronchoconstriction cause structural remodeling of the airway. Remodeling is a
      multicellular response to mucosal injury that results in epithelial cell-state
      changes, enhanced extracellular deposition, and expansion of pro-fibrotic
      myofibroblast populations. Areas covered: This manuscript overviews mechanistic
      studies identifying key sentinel cell populations in the airway and how pattern
      recognition signaling induces maladaptive mucosal changes and airway remodeling.
      Studies elucidating how NFkappaB couples with an atypical histone
      acetyltransferase, bromodomain-containing protein 4 (BRD4) that reprograms
      mucosal fibrogenic responses, are described. The approaches to development and
      characterization of selective inhibitors of epigenetic reprogramming on innate
      inflammation and structural remodeling in preclinical models are detailed. Expert
      commentary: Bronchiolar cells derived from Scgb1a1-expressing progenitors
      function as major sentinel cells of the airway, responsible for initiating
      antiviral and aeroallergen responses. In these sentinel cells, activation of
      innate inflammation is coupled to neutrophilic recruitment, mesenchymal
      transition and myofibroblast expansion. Therapeutics targeting the NFkB-BRD4 may
      be efficacious in reducing pathological effects of acute exacerbations in chronic
      lung disease.

PMID- 30241451
TI  - Veterinarians at the Connaught Medical Research Laboratories, 1931-72.
AB  - This study traces the changing mission of the University of Toronto's Connaught
      Medical Research Laboratories regarding the health of animals. We argue that the
      early work of Connaught's veterinarians in the 1930s and 1940s focused on the
      care for experimental animals as well as lending veterinary knowledge to problems
      in human medicine and public health. This gave way to a more direct focus on
      veterinary products after the Second World War. Connaught was motivated to enter
      the veterinary field in part to capitalize upon the growing market for veterinary
      medicines. It met with mixed success in this endeavour. Work was initially
      focused on livestock medicines and later expanded into products for companion
      animals, reflecting broader shifts in the veterinary profession and the economic
      value of animals during the 20th century.

PMID- 30241452
TI  - Serum betatrophin levels are reduced in patients with full-blown polycystic ovary
      syndrome.
AB  - Betatrophin is defined as a new marker in glucose homeostasis and lipid
      metabolism. We aimed to investigate the role of serum betatrophin in full-blown
      polycystic ovary syndrome (PCOS) patients and 47-aged healthy women, 51 full
      blown PCOS patients were included in this cross-sectional study. Betatrophin
      concentrations were significantly lower in PCOS group and displayed a positive
      correlation only with serum tryglyceride in control group (p < .05). A cutoff
      level (464.5 ng/L) was determined for betatrophin according to Receiver Operating
      Characteristic curve. Using this value, 64.7% of PCOS patients were classified as
      below the cutoff and in this group betatrophin was found to correlate negatively
      with fasting glucose, fasting insulin, and homeostasis model assessment of
      insulin resistance (p = .038, p = .020, and p = .014, respectively), and
      positively with total testosterone (p = .041). In the rest of PCOS cases (35.3%)
      who had betatrophin higher than cutoff, positive correlation was found with low
      density lipoprotein cholesterol (p = .009). In conclusion, betatrophin levels are
      reduced in full-blown PCOS patients who had worse metabolic phenotype.

PMID- 30241453
TI  - Do powered over-ground lower limb robotic exoskeletons affect outcomes in the
      rehabilitation of people with acquired brain injury?
AB  - PURPOSE: To assess the effects of lower limb robotic exoskeletons on outcomes in
      the rehabilitation of people with acquired brain injury. MATERIALS AND METHODS: A
      systematic review of seven electronic databases was conducted. The primary
      outcome of interest was neuromuscular function. Secondary outcomes included
      quality of life, mood, acceptability and safety. Studies were assessed for
      methodological quality and recommendations were made using the GRADE system.
      RESULTS: Of 2469 identified studies, 13 (n = 322) were included in the review.
      Five contained data suitable for meta-analysis. When the data were pooled, there
      were no differences between exoskeleton and control for 6-Minute Walk Test, Timed
      Up and Go or 10-Meter Walk Test. Berg Balance Scale outcomes were significantly
      better in controls (MD = 2.74, CI = 1.12-4.36, p = 0.0009). There were no severe
      adverse events but drop-outs were 11.5% (n = 37). No studies reported the effect
      of robotic therapy on quality of life or mood. Methodological quality was on
      average fair (15.6/27 on Downs and Black Scale). CONCLUSIONS: Only small numbers
      of people with acquired brain injury had data suitable for analysis. The
      available data suggests no more benefit for gait or balance with robotic therapy
      than conventional therapy. However, some important outcomes have not been studied
      and further well-conducted research is needed to determine whether such devices
      offer benefit over conventional therapy, in particular subgroups of those with
      acquired brain injury. Implications for Rehabilitation There is adequate evidence
      to recommend that powered over-ground lower limb robotic exoskeletons should not
      be used clinically in those with ABI, and that use should be restricted to
      research. Further research (controlled trials) with dependent ambulators is
      recommended. Research of other outcomes such as acceptability, spasticity,
      sitting posture, cardiorespiratory and psychological function, should be
      considered.

PMID- 30241455
TI  - Chlamydophila psittaci pneumonia associated to exposure to fulmar birds (Fulmaris
      glacialis) in the Faroe Islands.
AB  - BACKGROUND: For more than 200 years people in the Faroe Islands have supplemented
      their food by hunting different species of wild birds in the Faroe Islands.
      Traditionally, juvenile fulmars (Fulmarus glacialis) are caught at sea in late
      August. The fulmars may be infected or colonized with the bacterium Chlamydophila
      psittaci which may infect the hunter by the respiratory route and mostly presents
      as an atypical pneumonia, also called psittacosis or ornithosis or parrot fever.
      In the Faroe Islands it is called 'natasjuka' meaning 'fulmar disease'.
      Historically, it has also been called 'September Pneumonia' in the Faroe Islands.
      METHODS: A case series with patients infected with Chlamydophila psittaci.
      RESULTS: All four cases presented in this article occurred around the month of
      September. Improved hygiene measures during the last 50 years in handling the
      fulmar birds have led to a decline of verified psittacosis in the Faroe Islands.
      After the last two hunting seasons (2016-2017), four cases of psittacosis were
      diagnosed and treated in the Faroe Islands. Only nine cases of verified
      psittacosis have been reported to the Chief Medical Officer of the Faroe Islands
      during the last 27 years. CONCLUSIONS: There is an association between catching
      and handling Fulmarus glacialis and human psittacosis disease in the Faroe
      Islands. Clinicians treating patients with contact with fulmars should be aware
      of this zoonotic disease.

PMID- 30241454
TI  - Development of a BiTE(r)-mediated CD8+ cytotoxic T-lymphocyte activity assay to
      assess immunomodulatory potential of drug candidates in Cynomolgus macaque.
AB  - The immunotoxic potential of drug candidates is assessed through the examination
      of results from a variety of studies and endpoints. While the functional
      assessment of CD8+ cytotoxic T-lymphocytes (CTL) is well-characterized in the
      clinic, the lack of a robust macaque CTL functional assay has been an important
      hurdle in evaluating and accurately quantifying cell-mediated CD8+ T-cell
      effector responses in the nonclinical setting. This paper describes the
      development of an assay to measure CTL activity in peripheral blood mononuclear
      cells (PBMC) isolated from Cynomolgus macaques. A human EGFR/CD3 Bispecific T
      cell Engager (BiTE(r)) was used to mount a robust CD8+ T-cell response in the
      presence of target-expressing cells. Upon target engagement, degranulation of
      CD107a and production of interferon (IFN)-gamma both reliably indicated a robust
      functional response in CD8+ T-cells. The BiTE(r)-mediated stimulation method
      proved to be favorable when compared to other methods of stimulation in the
      absence of target cells. These studies demonstrated acceptable longitudinal
      variability of the functional assay and sensitivity to dexamethasone-mediated
      immunosuppression. Taken together, the results indicated an assay leveraging CD3
      bispecific antibodies and target-expressing cells can provide a robust approach
      to the in vitro or ex vivo assessment of CTL function in Cynomolgus macaques.
      Because the impairment of CTL activity by immunomodulators is recognized to be an
      important contributor to decreased antiviral defense and increased
      carcinogenicity risk, we believe that this novel assay to be a valuable addition
      to the immunotoxicology assessment of therapeutic drug candidates.

PMID- 30241456
TI  - "Yes It Is Phenomenological": A Reply to Max Van Manen's Critique of
      Interpretative Phenomenological Analysis.
AB  - In this article, I present a rebuttal of Max Van Manen's critique of
      interpretative phenomenological analysis (IPA). Unfortunately, Van Manen's piece
      contains a series of misrepresentations of IPA and its history. Here, I answer
      these misrepresentations and present IPA as subscribing, and contributing, to a
      broad and holistic phenomenology concerned with both prereflective and reflective
      domains of lived experience. I contend that IPA has much to offer to our
      understanding of the experience of health and illness, where participants are
      spontaneously and actively engaged in making sense of the significant and
      unexpected things that happen to them.

PMID- 30241458
TI  - Asymmetric expression of H19 and ADIPOQ in concave/convex paravertebral muscles
      is associated with severe adolescent idiopathic scoliosis.
AB  - BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common paediatric
      spinal deformity. The etiology and pathology of AIS remain unexplained, and have
      been reported to involve a combination of genetic and epigenetic factors. Since
      paravertebral muscle imbalance plays an important role in the onset and
      progression of scoliosis, we aimed to investigate transcriptomic differences by
      RNA-seq and identify significantly differentially expressed transcripts in two
      sides of paravertebral muscle in AIS. METHODS: RNA-seq was performed on 5 pairs
      of paravertebral muscle from 5 AIS patients. Significantly differentially
      expressed transcripts were validated by quantitative reverse polymerase chain
      reaction. Gene expression difference was correlated to clinical characteristics.
      RESULTS: We demonstrated that ADIPOQ mRNA and H19 is significantly differentially
      expressed between two sides of paravertebral muscle, relatively specific in the
      context of AIS. Relatively low H19 and high ADIPOQ mRNA expression levels in
      concave-sided muscle are associated with larger spinal curve and earlier age at
      initiation. We identified miR-675-5p encoded by H19 as a mechanistic regulator of
      ADIPOQ expression in AIS. We demonstrated that significantly reduced CCCTC
      binding factor (CCTF) occupancy in the imprinting control region (ICR) of the H19
      gene in the concave-sided muscle contributes to down-regulated H19 expression.
      CONCLUSIONS: RNA-seq revealed transcriptomic differences between two sides of
      paravertebral muscle in AIS patients. Our findings imply that transcriptomic
      differences caused by epigenetic factors in affected individuals may account for
      the structural and functional imbalance of paravertebral muscle, which can expand
      our etiologic understanding of this disease.

PMID- 30241459
TI  - Identifying protein complexes based on node embeddings obtained from protein
      protein interaction networks.
AB  - BACKGROUND: Protein complexes are one of the keys to deciphering the behavior of
      a cell system. During the past decade, most computational approaches used to
      identify protein complexes have been based on discovering densely connected
      subgraphs in protein-protein interaction (PPI) networks. However, many true
      complexes are not dense subgraphs and these approaches show limited performances
      for detecting protein complexes from PPI networks. RESULTS: To solve these
      problems, in this paper we propose a supervised learning method based on network
      node embeddings which utilizes the informative properties of known complexes to
      guide the search process for new protein complexes. First, node embeddings are
      obtained from human protein interaction network. Then the protein interactions
      are weighted through the similarities between node embeddings. After that, the
      supervised learning method is used to detect protein complexes. Then the random
      forest model is used to filter the candidate complexes in order to obtain the
      final predicted complexes. Experimental results on real human and yeast protein
      interaction networks show that our method effectively improves the performance
      for protein complex detection. CONCLUSIONS: We provided a new method for
      identifying protein complexes from human and yeast protein interaction networks,
      which has great potential to benefit the field of protein complex detection.

PMID- 30241460
TI  - Progressive multiple sequence alignment with indel evolution.
AB  - BACKGROUND: Sequence alignment is crucial in genomics studies. However, optimal
      multiple sequence alignment (MSA) is NP-hard. Thus, modern MSA methods employ
      progressive heuristics, breaking the problem into a series of pairwise alignments
      guided by a phylogeny. Changes between homologous characters are typically
      modelled by a Markov substitution model. In contrast, the dynamics of indels are
      not modelled explicitly, because the computation of the marginal likelihood under
      such models has exponential time complexity in the number of taxa. But the
      failure to model indel evolution may lead to artificially short alignments due to
      biased indel placement, inconsistent with phylogenetic relationship. RESULTS:
      Recently, the classical indel model TKF91 was modified to describe indel
      evolution on a phylogeny via a Poisson process, termed PIP. PIP allows to compute
      the joint marginal probability of an MSA and a tree in linear time. We present a
      new dynamic programming algorithm to align two MSAs -represented by the
      underlying homology paths- by full maximum likelihood under PIP in polynomial
      time, and apply it progressively along a guide tree. We have corroborated the
      correctness of our method by simulation, and compared it with competitive methods
      on an illustrative real dataset. CONCLUSIONS: Our MSA method is the first
      polynomial time progressive aligner with a rigorous mathematical formulation of
      indel evolution. The new method infers phylogenetically meaningful gap patterns
      alternative to the popular PRANK, while producing alignments of similar length.
      Moreover, the inferred gap patterns agree with what was predicted qualitatively
      by previous studies. The algorithm is implemented in a standalone C++ program:
      https://github.com/acg-team/ProPIP . Supplementary data are available at BMC
      Bioinformatics online.

PMID- 30241461
TI  - Over-expressed microRNA-181a reduces glomerular sclerosis and renal tubular
      epithelial injury in rats with chronic kidney disease via down-regulation of the
      TLR/NF-kappaB pathway by binding to CRY1.
AB  - BACKGROUND: MicroRNAs (miRNAs) contribute to the progression of chronic kidney
      disease (CKD) by regulating renal homeostasis. This study explored the effects of
      miR-181a on CKD through the Toll-like receptor (TLR)/nuclear factor-kappa B (NF
      kappaB) pathway by binding to CRY1. METHODS: Seventy male rats were selected and
      assigned into specific groups: miR-181a mimic, miR-181a inhibitor, and siRNA
      against CRY1, with each group undergoing different treatments to investigate many
      different outcomes. First, 24-h urinary protein was measured. ELISA was used to
      determine the serum levels of SOD, ROS, MDA, IL-1beta, IL-6, and TNF-alpha.
      Biochemical tests for renal function were performed to measure albumin, uric
      acid, and urea in urine and urea nitrogen and creatinine in serum. The
      glomerulosclerosis index (GSI) and renal tubular epithelial (RTE) cell apoptosis
      were detected using PASM staining and TUNEL staining, respectively. Finally, RT
      qPCR and western blot were done to determine miR-181a, CRY1, TLR2, TLR4, and NF
      kappaB expression. RESULTS: CRY1 is the target gene of miR-181a, according to a
      target prediction program and luciferase assay. Rats diagnosed with CKD presented
      increases in 24-h urinary protein; GSI; RTE cell apoptosis rate; serum ROS, MDA,
      IL-1beta, IL-6, and TNF-alpha; and CRY1, TLR2, TLR4, and NF-kappaB expression, as
      well as decreases in SOD level and miR-181a expression. Following transfection
      with either the miR-181a mimic or si-CRY1, 24-h urinary protein, renal damage,
      GSI, and cell apoptosis rate were all decreased. In addition, the overexpression
      of miR-181a or inhibition of CRY1 alleviated the degree of kidney injury through
      suppression of the TLR/NF-kappaB pathway. CONCLUSION: miR-181a alleviates both GS
      and RTE injury in CKD via the down-regulation of the CRY1 gene and the TLR/NF
      kappaB pathway.

PMID- 30241462
TI  - Chromosomal variation among populations of a fungus-farming ant: implications for
      karyotype evolution and potential restriction to gene flow.
AB  - BACKGROUND: Intraspecific variation in chromosome structure may cause genetic
      incompatibilities and thus provides the first step in the formation of species.
      In ants, chromosome number varies tremendously from 2n = 2 to 2n = 120, and
      several studies have revealed considerable variation in karyotype within species.
      However, most previous studies were limited to the description of chromosome
      number and morphology, and more detailed karyomorphometric analyses may reveal
      additional, substantial variation. Here, we studied karyotype length, genome
      size, and phylogeography of five populations of the fungus-farming ant
      Trachymyrmex holmgreni in order to detect potential barriers to gene flow.
      RESULTS: Chromosome number and morphology did not vary among the five
      populations, but karyotype length and genome size were significantly higher in
      the southernmost populations than in the northern populations of this ant.
      Individuals or colonies with different karyotype lengths were not observed.
      Karyotype length variation appears to result from variation in centromere length.
      CONCLUSION: T. holmgreni shows considerable variation in karyotype length and
      might provide a second example of centromere drive in ants, similar to what has
      previously been observed in Solenopsis fire ants. Whether this variation leads to
      genetic incompatibilities between the different populations remains to be
      studied.

PMID- 30241463
TI  - Overlapping group screening for detection of gene-gene interactions: application
      to gene expression profiles with survival trait.
AB  - BACKGROUND: The development of a disease is a complex process that may result
      from joint effects of multiple genes. In this article, we propose the overlapping
      group screening (OGS) approach to determining active genes and gene-gene
      interactions incorporating prior pathway information. The OGS method is developed
      to overcome the challenges in genome-wide data analysis that the number of the
      genes and gene-gene interactions is far greater than the sample size, and the
      pathways generally overlap with one another. The OGS method is further proposed
      for patients' survival prediction based on gene expression data. RESULTS:
      Simulation studies demonstrate that the performance of the OGS approach in
      identifying the true main and interaction effects is good and the survival
      prediction accuracy of OGS with the Lasso penalty is better than the ordinary
      Lasso method. In real data analysis, we identify several significant genes and/or
      epistasis interactions that are associated with clinical survival outcomes of
      diffuse large B-cell lymphoma (DLBCL) and non-small-cell lung cancer (NSCLC) by
      utilizing prior pathway information from the KEGG pathway and the GO biological
      process databases, respectively. CONCLUSIONS: The OGS approach is useful for
      selecting important genes and epistasis interactions in the ultra-high
      dimensional feature space. The prediction ability of OGS with the Lasso penalty
      is better than existing methods. The OGS approach is generally applicable to
      various types of outcome data (quantitative, qualitative, censored event time
      data) and regression models (e.g. linear, logistic, and Cox's regression models).

PMID- 30241464
TI  - Initial state perturbations as a validation method for data-driven fuzzy models
      of cellular networks.
AB  - BACKGROUND: Data-driven methods that automatically learn relations between
      attributes from given data are a popular tool for building mathematical models in
      computational biology. Since measurements are prone to errors, approaches dealing
      with uncertain data are especially suitable for this task. Fuzzy models are one
      such approach, but they contain a large amount of parameters and are thus
      susceptible to over-fitting. Validation methods that help detect over-fitting are
      therefore needed to eliminate inaccurate models. RESULTS: We propose a method to
      enlarge the validation datasets on which a fuzzy dynamic model of a cellular
      network can be tested. We apply our method to two data-driven dynamic models of
      the MAPK signalling pathway and two models of the mammalian circadian clock. We
      show that random initial state perturbations can drastically increase the mean
      error of predictions of an inaccurate computational model, while keeping errors
      of predictions of accurate models small. CONCLUSIONS: With the improvement of
      validation methods, fuzzy models are becoming more accurate and are thus likely
      to gain new applications. This field of research is promising not only because
      fuzzy models can cope with uncertainty, but also because their run time is short
      compared to conventional modelling methods that are nowadays used in systems
      biology.

PMID- 30241465
TI  - Linkage analysis and QTL mapping in a tetraploid russet mapping population of
      potato.
AB  - BACKGROUND: Genome-wide single nucleotide polymorphism (SNP) markers coupled with
      allele dosage information has emerged as a powerful tool for studying complex
      traits in cultivated autotetraploid potato (Solanum tuberosum L., 2n = 4* = 48).
      To date, this approach has been effectively applied to the identification of
      quantitative trait loci (QTLs) underlying highly heritable traits such as disease
      resistance, but largely unexplored for traits with complex patterns of
      inheritance. RESULTS: In this study, an F1 tetraploid russet mapping population
      (162 individuals) was evaluated for multiple quantitative traits over two years
      and two locations to identify QTLs associated with tuber sugar concentration,
      processing quality, vine maturity, and other high-value agronomic traits. We
      report the linkage maps for the 12 potato chromosomes and the QTL location with
      corresponding genetic models and candidate SNPs explaining the highest phenotypic
      variation for tuber quality and maturity related traits. Significant QTLs for
      tuber glucose concentration and tuber fry color were detected on chromosomes 4,
      5, 6, 10, and 11. Collectively, these QTLs explained between 24 and 46% of the
      total phenotypic variation for tuber glucose and fry color, respectively. The QTL
      on chromosome 10 was associated with apoplastic invertases, with 'Premier Russet'
      contributing the favorable allele for fry processing quality. On chromosome 5,
      minor-effect QTLs for tuber glucose concentration and fry color co-localized with
      various major-effect QTLs, including vine maturity, growth habit, tuber shape,
      early blight (Altenaria tenuis), and Verticillium wilt (Verticillium spp.).
      CONCLUSIONS: Linkage analysis and QTL mapping in a russet mapping population
      (A05141) using SNP dosage information successfully identified favorable alleles
      and candidate SNPs for resistance to the accumulation of tuber reducing sugars.
      These novel markers have a high potential for the improvement of tuber processing
      quality. Moreover, the discovery of different genetic models for traits with
      overlapping QTLs at the maturity locus clearly suggests an independent genetic
      control.

PMID- 30241466
TI  - ECPred: a tool for the prediction of the enzymatic functions of protein sequences
      based on the EC nomenclature.
AB  - BACKGROUND: The automated prediction of the enzymatic functions of
      uncharacterized proteins is a crucial topic in bioinformatics. Although several
      methods and tools have been proposed to classify enzymes, most of these studies
      are limited to specific functional classes and levels of the Enzyme Commission
      (EC) number hierarchy. Besides, most of the previous methods incorporated only a
      single input feature type, which limits the applicability to the wide functional
      space. Here, we proposed a novel enzymatic function prediction tool, ECPred,
      based on ensemble of machine learning classifiers. RESULTS: In ECPred, each EC
      number constituted an individual class and therefore, had an independent learning
      model. Enzyme vs. non-enzyme classification is incorporated into ECPred along
      with a hierarchical prediction approach exploiting the tree structure of the EC
      nomenclature. ECPred provides predictions for 858 EC numbers in total including 6
      main classes, 55 subclass classes, 163 sub-subclass classes and 634 substrate
      classes. The proposed method is tested and compared with the state-of-the-art
      enzyme function prediction tools by using independent temporal hold-out and no
      Pfam datasets constructed during this study. CONCLUSIONS: ECPred is presented
      both as a stand-alone and a web based tool to provide probabilistic enzymatic
      function predictions (at all five levels of EC) for uncharacterized protein
      sequences. Also, the datasets of this study will be a valuable resource for
      future benchmarking studies. ECPred is available for download, together with all
      of the datasets used in this study, at: https://github.com/cansyl/ECPred . ECPred
      webserver can be accessed through http://cansyl.metu.edu.tr/ECPred.html .

PMID- 30241467
TI  - RNA-seq analysis of gene expression changes during pupariation in Bactrocera
      dorsalis (Hendel) (Diptera: Tephritidae).
AB  - BACKGROUND: The oriental fruit fly, Bactrocera dorsalis (Hendel) has been
      considered to be one of the most important agricultural pest around the world. As
      a holometabolous insect, larvae must go through a metamorphosis process with
      dramatic morphological and structural changes to complete their development. To
      better understand the molecular mechanisms of these changes, RNA-seq of B.
      dorsalis from wandering stage (WS), late wandering stage (LWS) and white puparium
      stage (WPS) were performed. RESULTS: In total, 11,721 transcripts were obtained,
      out of which 1914 genes (578 up-regulated and 1336 down-regulated) and 2047 genes
      (655 up-regulated and 1392 down-regulated) were found to be differentially
      expressed between WS and LWS, as well as between WS and WPS, respectively. Of
      these DEGs, 1862 and 1996 genes were successfully annotated in various databases.
      The analysis of RNA-seq data together with qRT-PCR validation indicated that
      during this transition, the genes in the oxidative phosphorylation pathway, and
      genes encoding P450s, serine protease inhibitor, and cuticular proteins were down
      regulated, while the serine protease genes were up-regulated. Moreover, we found
      some 20-hydroxyecdysone (20E) biosynthesis and signaling pathway genes had a
      higher expression in the WS, while the genes responsible for juvenile hormone
      (JH) synthesis, degradation, signaling and transporter pathways were down
      regulated, suggesting these genes might be involved in the process of larval
      pupariation in B. dorsalis. For the chitinolytic enzymes, the genes encoding
      chitinases (chitinase 2, chitinase 5, chitinase 8, and chitinase 10) and chitin
      deacetylase might play the crucial role in the degradation of insect chitin with
      their expressions significantly increased during the transition. Here, we also
      found that chitin synthase 1A might be involved in the chitin synthesis of
      cuticles during the metamorphosis in B. dorsalis. CONCLUSIONS: Significant
      changes at transcriptional level were identified during the larval pupariation of
      B. dorsalis. Importantly, we also obtained a vast quantity of RNA-seq data and
      identified metamorphosis associated genes, which would all help us to better
      understand the molecular mechanism of metamorphosis process in B. dorsalis.

PMID- 30241468
TI  - Characterization of a strong and constitutive promoter from the Arabidopsis
      serine carboxypeptidase-like gene AtSCPL30 as a potential tool for crop
      transgenic breeding.
AB  - BACKGROUND: Transgenic technology has become an important technique for crop
      genetic improvement. The application of well-characterized promoters is essential
      for developing a vector system for efficient genetic transformation. Therefore,
      isolation and functional validation of more alternative constitutive promoters to
      the CaMV35S promoter is highly desirable. RESULTS: In this study, a 2093-bp
      sequence upstream of the translation initiation codon ATG of AtSCPL30 was
      isolated as the full-length promoter (PD1). To characterize the AtSCPL30 promoter
      (PD1) and eight 5' deleted fragments (PD2-PD9) of different lengths were fused
      with GUS to produce the promoter::GUS plasmids and were translocated into
      Nicotiana benthamiana. PD1-PD9 could confer strong and constitutive expression of
      transgenes in almost all tissues and development stages in Nicotiana benthamiana
      transgenic plants. Additionally, PD2-PD7 drove transgene expression consistently
      over twofold higher than the well-used CaMV35S promoter under normal and stress
      conditions. Among them, PD7 was only 456 bp in length, and its transcriptional
      activity was comparable to that of PD2-PD6. Moreover, GUS transient assay in the
      leaves of Nicotiana benthamiana revealed that the 162-bp (- 456~ - 295 bp) and
      111-bp (- 294~ - 184 bp) fragments from the AtSCPL30 promoter could increase the
      transcriptional activity of mini35S up to 16- and 18-fold, respectively.
      CONCLUSIONS: As a small constitutive strong promoter of plant origin, PD7 has the
      advantage of biosafety and reduces the probability of transgene silencing
      compared to the virus-derived CaMV35S promoter. PD7 would also be an alternative
      constitutive promoter to the CaMV35S promoter when multigene transformation was
      performed in the same vector, thereby avoiding the overuse of the CaMV35S
      promoter and allowing for the successful application of transgenic technology.
      And, the 162- and 111-bp fragments will also be very useful for synthetic
      promoter design based on their high enhancer activities.

PMID- 30241469
TI  - A trend towards a more intense adjuvant treatment of low-grade-gliomas in
      tertiary centers in Germany after RTOG 9802 - results from a multi-center survey.
AB  - BACKGROUND: The treatment recommendations for Low-grade Gliomas (LGG) underwent
      profound changes due to results from RTOG 9802 published in April 2016. This work
      aims to investigate whether the results from the trial were already incorporated
      into the treatment recommendations at German oncology centers before an update of
      the official guidelines. METHODS: An online based questionnaire with questions
      covering all aspects of adjuvant treatments of LGGs was generated, including
      three cases with distinct clinical situations. We contacted all members of the
      neuro-oncologic working group (NOA) of the German Cancer Society (DKG) as well as
      all German-speaking members of the European Low-Grade Glioma Network via E-mail.
      RESULTS: We collected 38 responses. All responders were at least specialists;
      they predominantly worked at tertiary hospitals with a high volume of LGGs
      treated annually (75% with more than 10 cases per year). All responders stated to
      consent treatment recommendation for LGGs within interdisciplinary oncologic
      boards. The treatment recommendations for LGGs changed profoundly between 2015
      and 12/2016. There is a trend towards PCV-based multimodal treatments, especially
      for oligodendroglial LGGs, as well as a trend away from watchful-waiting-policies
      for astrocytic LGGs. CONCLUSION: Neurooncologists do adapt results from clinical
      trials quickly. None the less, there is still an immense heterogeneity within the
      treatment recommendations, predominantly for astrocytic LGGs. Well planned
      clinical trials and concise treatment recommendations are warranted;
      additionally, individual counseling of patients is essential.

PMID- 30241470
TI  - Predictive and prognostic value of Matrix metalloproteinase (MMP) - 9 in
      neoadjuvant chemotherapy for triple-negative breast cancer patients.
AB  - BACKGROUND: This study aimed to investigate the clinical utility of serum and
      histological MMP-9 detection during neoadjuvant chemotherapy (NAC) for triple
      negative breast cancer (TNBC). METHODS: A total of 303 TNBC patients who
      underwent weekly paclitaxel plus carboplatin treatments followed by surgical
      resection were included in this study. Enzyme-linked immunosorbent assay (ELISA)
      was used to detect the serum level of Matrix metalloproteinase-9 (sMMP-9) at
      baseline and prior to surgery. Immunohistochemistry was used to detect
      histological MMP-9 (hMMP-9) expression in patients with residual tumors after
      NAC. The value of MMP-9 to predict the response to NAC and patient survival was
      studied. RESULTS: Of the 303 patients, 103 (34.0%) patients experienced
      pathological complete response (pCR) after completion of NAC. Univariate and
      multivariate analyses revealed that the relative change in sMMP-9, rather than
      sMMP-9 at baseline or surgery, had a remarkable predictive value for pCR. Each 1
      ng/ml decrease in sMMP-9 after NAC was shown to result in a 0.3% increase in pCR
      rate. Additionally, in survival analyses, hMMP-9 expression in residual tumors
      was independently correlated with disease-free survival for non-pCR responders (P
      < 0.001). CONCLUSIONS: Our findings indicate that monitoring serum MMP-9 and
      detection of histological MMP-9 could help identify TNBC patients who will
      respond to NAC and will display varying risks of disease relapse. MMP-9 may serve
      as a predictive and prognostic biomarker for tailoring and modifying the NAC
      strategy for TNBC.

PMID- 30241471
TI  - New enrollment under the affordable care act: leading the way for community
      health centers in Southern California.
AB  - BACKGROUND: The Affordable Care Act (ACA) has improved healthcare access in the
      community health centers that have played a critical role in enrolling low income
      and minority patients. This study examined the ACA enrollment for one of the
      largest federally qualified community health centers in the country. METHODS: An
      exploratory sequential mixed method study was used as the main qualitative and
      quantitative approach for this study. Key stakeholders (n = 6) were interviewed
      as part of the qualitative component, and information about barriers and best
      practices were acquired. As part of the quantitative analysis, we examined cross
      sectional data among 59,272 AltaMed enrollees in 2013-2015. We analyzed data on
      age, gender, language, ethnicity, and enrollment periods. The interviews were
      conducted first and followed by the data analysis. RESULTS: AltaMed was the top
      enroller of patients in ACA insurance plans in California (2013-14 and 2014-15)
      through the state exchange and Medicaid expansion. Using key stakeholder
      interviews, 5 main barriers were identified and 5 innovative solutions that
      allowed AltaMed to enroll people into the state exchange and Medicaid expansion.
      Barriers to enrollment included training, new workflows, and enrollment of Young
      Invincibles, and these enrollment barriers were overcome with community health
      workers. CONCLUSION: Enrollment barriers were overcome through AltaMed's
      community-based approach and long term community partnerships.

PMID- 30241472
TI  - Flocculation characteristics of a bioflocculant produced by the actinomycete
      Streptomyces sp. hsn06 on microalgae biomass.
AB  - BACKGROUND: Microbial flocculation is a good choice for harvest of microalgae
      biomass, which has gained extensive attention. There have been carried out
      massive studies in bacterial flocculation, many bacterial strains with
      flocculation activity were isolated and different types of bioflocculants were
      produced. However, harvest of algal biomass by bioflocculants which produced from
      actinomycete are deficiency. In this study, the bioflocculant from an
      actinomycete Streptomyces sp. hsn06 could be used to harvest Chlorella vulgaris
      biomass. RESULTS: Consecutive treatment with 20 mg.L- 1 bioflocculant and 5 mM
      CaCl2 for 5 min showed the highest flocculating activity. The bioflocculant was a
      nonprotein substance with thermal stability and pH stability, which can be used
      in comprehensive applications. Chemical analysis of the bioflocculant indicated
      that it is a small molecule substance of moderate polarity with containing triple
      bond and cumulated double bonds. Algal temperature, pH, and metal ions showed
      great effects on the flocculation efficiency of the bioflocculant. CONCLUSIONS:
      The bioflocculant produced by Streptomyces sp. hsn06 possesses the potential to
      harvest algal biomass with high-efficiency.

PMID- 30241474
TI  - AstigMATIC: an automatic tool for standard astigmatism vector analysis.
AB  - BACKGROUND: Standardization for reporting medical outcomes facilitates clinical
      study comparisons and has a fundamental role on research reproducibility. In this
      context, we present AstigMATIC, a free standalone application for automated
      standardized astigmatism vector analyses in corneal and intraocular refractive
      surgeries. AstigMATIC uses a simple graphical user interface (GUI) and allows the
      simultaneous display and analysis of astigmatism magnitude and axis. RESULTS: The
      software produces the four following standard graphs according to the standards
      of the Alpins Method; 1-Target-Induced Astigmatism Vector, 2- Surgically-Induced
      Astigmatism Vector, 3-Difference Vector and 4-Correction Index. Vector means with
      X and Y standard deviations are automatically calculated and displayed on the
      corresponding single-angle vector plots (0 to 180 degrees ). Data points are
      entered into a simplified GUI with no need for command line input. The standard
      graphs can be easily exported as high-resolution TIFF images for figures to use
      in production and presentations. CONCLUSIONS: AstigMATIC enables the user to
      easily and efficiently analyze vectorial astigmatism outcomes using the
      standardized Alpins Method for post-surgical astigmatism.

PMID- 30241473
TI  - Gastroesophageal reflux disease and its related factors among women of
      reproductive age: Korea Nurses' Health Study.
AB  - BACKGROUND: Recently, the number of patients diagnosed with gastroesophageal
      reflux disease (GERD) has increased in Korea. Risk factors of GERD include age,
      sex, medication use, lack of physical exercise, increased psychological stress,
      low or high body mass index (BMI), unhealthy eating habits, increased alcohol
      consumption, and cigarette smoking. However, few studies examined the major
      factors affecting GERD in women of childbearing age. Therefore, this study
      assessed the risk factors of GERD among 20,613 female nurses of reproductive age
      using data from the Korea Nurses' Health Study. METHODS: Participants were
      recruited from July 2013 to November 2014. They provided their history of GERD 1
      year prior to data collection, along with information on their demographic
      characteristics, health-related behaviors, diet, medical history, and physical
      and psychological factors. Of the total sample, 1184 individuals with GERD
      diagnosed in the year prior to the study were identified. Propensity score
      matching was used for analysis. RESULTS: Cigarette smoking, increased alcohol
      consumption, low or high BMI, depression, and increased psychosocial stress were
      associated with the prevalence of GERD among Korean young women. Multivariate
      ordinal logistic regression analysis revealed significant positive relationships
      between GERD and being a former smoker; having a low (< 18.5 kg/m2) or high BMI
      (> 23 kg/m2); and having mild, moderate, moderately severe, and severe
      depression. CONCLUSIONS: Smoking, BMI, and depression were associated with GERD.
      To reduce this risk among female nurses, intervention strategies are required to
      help nurses maintain a normal weight and manage their depression.

PMID- 30241475
TI  - Study protocol: healthy urban living and ageing in place (HULAP): an
      international, mixed methods study examining the associations between physical
      activity, built and social environments for older adults the UK and Brazil.
AB  - BACKGROUND: The ability to 'age in place' is dependent on a range of inter
      personal, social and built environment attributes, with the latter being a key
      area for potential intervention. There is an emerging body of evidence that
      indicates the type of built environment features that may best support age
      friendly communities, but there is a need to expand and consolidate this, while
      generating a better understanding of how on how research findings can be most
      effectively be translated in to policy and practice. METHODS: The study is based
      on two case study cities, Curtiba (Brazil) and Belfast (UK), which have highly
      contrasting physical, social and policy environments. The study deploys a mix
      methods approach, mirrored in each city. This includes the recruitment of 300
      participants in each city to wear GPS and accelerometers, a survey capturing
      physical functioning and other personal attributes, as well as their perception
      of their local environment using NEWS-A. The study will also measure the built
      environments of the cities using GIS and develop a tool for auditing the routes
      used by participants around their neighbourhoods. The study seeks to
      comparatively map the policy actors and resources involved in healthy ageing in
      the two cities through interviews, focus groups and discourse analysis. Finally,
      the study has a significant knowledge exchange component, including the
      development of a tool to assess the capacities of both researchers and research
      users to maximise the impact of the research findings. DISCUSSION: The HULAP
      study has been designed and implemented by a multi-disciplinary team and
      integrates differing methodologies to purposefully impact on policy and practice
      on healthy ageing in high and low-middle income countries. It has particular
      strengths in its combination of objective and self-reported measures using
      validated tools and the integration of GPS, accelerometer and GIS data to provide
      a robust assessment of 'spatial energetics'. The strong knowledge exchange strand
      means that the study is expected to also contribute to our understanding of how
      to maximise research impact in this field and create effective evidence for
      linking older adult's physical activity with the social, built and policy
      environments.

PMID- 30241476
TI  - The supportive care needs of women experiencing gynaecological cancer: a Western
      Australian cross-sectional study.
AB  - BACKGROUND: Women diagnosed with gynaecological cancer experience supportive care
      needs that require care provision to reduce the impact on their lives.
      International evidence suggests supportive care needs of women with
      gynaecological cancer are not being met and provision of holistic care is a
      priority area for action. Knowledge on gynaecological cancer supportive care
      needs is limited, specifically comparison of needs and cancer gynaecological
      subtype. Our aim was to identify supportive care needs of Western Australian
      women experiencing gynaecological cancer, their satisfaction with help and
      explore associations between participant's demographic characteristics and
      identified needs. METHODS: A cross-sectional design incorporating a modified
      version of the Supportive Care Needs Survey - short form (SCNS-SF34) assessed 37
      supportive care needs under five domains in conjunction with demographic data.
      Three hundred and forty three women with gynaecological cancer attending a
      tertiary public referral hospital completed the survey over 12 months.
      Statistical analysis was performed using the R environment for statistical
      computing. A linear regression model was fitted with factor scores for each
      domain and demographic characteristics as explanatory variables. RESULTS: Three
      hundred and three women (83%) identified at least one moderate or high level
      supportive care need. The five highest ranked needs were, 'being informed about
      your test results as soon as feasible' (54.8%), 'fears about cancer spreading'
      (53.7%), 'being treated like a person not just another case' (51.9%), 'being
      informed about cancer which is under control or diminishing (that is, remission)'
      (50.7%), and 'being adequately informed about the benefits and side-effects of
      treatments before you choose to have them' (49.9%). Eight of the top ten needs
      were from the 'health system and information' domain. Associations between
      supportive care items and demographic variables revealed 'cancer type', and 'time
      since completion of treatment' had no impact on level of perceived need for any
      domain. CONCLUSIONS: Western Australian women with gynaecological cancer
      identified a high level of supportive care needs. The implementation of a
      supportive care screening tool is recommended to ensure needs are identified and
      care is patient-centred. Early identification and management of needs may help to
      reduce the burden on health system resources for managing ongoing needs.

PMID- 30241477
TI  - Comparison of a sports-hydration drink containing high amylose starch with usual
      hydration practice in Australian rules footballers during intense summer
      training.
AB  - BACKGROUND: Fluid deficits exceeding 1.6% can lead to physical and cognitive
      impairment in athletes. Sport drinks used by athletes are often hyper-osmolar but
      this is known to be suboptimal for rehydration in medical settings and does not
      utilize colonic absorptive capacity. Colonic absorption can be enhanced by
      fermentative production of short chain fatty acids (SCFA) from substrates such as
      high amylose maize starch (HAMS). This study therefore compared, in elite
      Australian Football League (AFL) players at the height of outdoor summer
      training, a novel dual-action sports oral rehydration strategy that contained
      HAMS as well as glucose, to their usual rehydration practices (Control). The
      primary outcome markers of hydration were hematocrit and body weight. METHODS: A
      randomized single-blind crossover study was undertaken in thirty-one AFL players;
      twenty-seven completed the study which was conducted on four days (two days in
      the Intervention arm and two in Control arm). The Intervention arm was comprised
      a 50-100 g evening preload of an acetylated HAMS (Ingredion Pty Ltd) followed by
      consumption of a specially formulated sports oral rehydration solution (SpORS)
      drink during intense training and recovery. Players followed their usual
      hydration routine in the Control arm. Quantitative assessments of body weight,
      hematocrit and urine specific gravity were made at three time-points on each day
      of training: pre-training, post-training (90 min), and at end of recovery (30-60
      min later). GPS tracking monitored player exertion. RESULTS: Across the three
      time-points, hematocrit was significantly lower and body weight significantly
      higher in Intervention compared to Control arms (p < 0.02 and p = 0.001
      respectively, mixed effects model). Weights were significantly heavier at all
      three assessment points for Intervention compared to Control arms (Delta = 0.30
      +/- 0.13, p = 0.02 pre-training; Delta = 0.43 +/- 0.14, p = 0.002 post training;
      and Delta = 0.68 +/- 0.14, p < 0.001 for recovery). Between the pre-training and
      end-of-recovery assessments, the Control arm lost 0.80 kg overall compared with
      0.12 kg in the Intervention arm, an 85% lower reduction of bodyweight across the
      assessment period. CONCLUSION: The combination of the significantly lower
      hematocrit and increased body weight in the Intervention arm represents better
      hydration not only at the end of training as well as following a recovery period
      but also at its commencement. The magnitude of the benefit seems sufficient to
      have an impact on performance and further studies to test this possibility are
      now indicated. TRIAL REGISTRATION: Trial is listed on the Australian New Zealand
      Clinical Trials Registry ( ACTRN 12613001373763 ).

PMID- 30241478
TI  - TEM8 functions as a receptor for uPA and mediates uPA-stimulated EGFR
      phosphorylation.
AB  - BACKGROUND: TEM8 is a cell membrane protein predominantly expressed in tumor
      endothelium, which serves as a receptor for the protective antigen (PA) of
      anthrax toxin. However, the physiological ligands for TEM8 remain unknown.
      RESULTS: Here we identified uPA as an interacting partner of TEM8. Binding of uPA
      stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and
      ERK1/2. Finally, TEM8-Fc, a recombinant fusion protein comprising the
      extracellular domain of human TEM8 linked to the Fc portion of human IgG1,
      efficiently abrogated the interaction between uPA and TEM8, blocked uPA-induced
      migration of HepG2 cells in vitro and inhibited the growth and metastasis of
      human MCF-7 xenografts in vivo. uPA, TEM8 and EGFR overexpression and ERK1/2
      phosphorylation were found co-located on frozen cancer tissue sections.
      CONCLUSIONS: Taken together, our data provide evidence that TEM8 is a novel
      receptor for uPA, which may play a significant role in the regulation of tumor
      growth and metastasis.

PMID- 30241480
TI  - Towards a new set of classification criteria for PFAPA syndrome.
AB  - BACKGROUND: Diagnosis of Periodic Fever, Aphthous stomatitis, Pharyngitis and
      Cervical Adenitis (PFAPA) syndrome is currently based on the modified Marshall's
      criteria, but no validated evidence based classification criteria for PFAPA has
      been established so far. METHODS: A multistep process, based on the Delphi and
      Nominal Group Technique was conducted. After 2 rounds of e-mail Delphi survey
      involving 21 experts in autoinflammation we obtained a list of variables that
      were discussed in an International Consensus Conference. Variables reaching the
      80% of consensus between participants were included in the new classification
      criteria. In the second phase the new classification criteria and the modified
      Marshall's criteria were applied on a cohort of 80 pediatric PFAPA patients to
      compare their performance. RESULTS: The Delphi Survey was sent to 22
      participants, 21 accepted to participate. Thirty variables were obtained from the
      survey and have been discussed at the Consensus Conference. Through the Nominal
      Group Technique we obtained a new set of classification criteria. These criteria
      were more restrictive in respect to the modified Marshall's criteria when applied
      on our cohort of patients. CONCLUSION: Our work led us to identify a new set of
      classification criteria for PFAPA syndrome, but they resulted to be too
      restrictive to be applied in daily clinical practice for the diagnosis of PFAPA.

PMID- 30241479
TI  - Microglia prevent peripheral immune cell invasion and promote an anti
      inflammatory environment in the brain of APP-PS1 transgenic mice.
AB  - BACKGROUND: Undoubtedly, neuroinflammation is a major contributor to Alzheimer's
      disease (AD) progression. Neuroinflammation is characterized by the activity of
      brain resident glial cells, in particular microglia, but also by peripheral
      immune cells, which infiltrate the brain at certain stages of disease
      progression. The specific role of microglia in shaping AD pathology is still
      controversially discussed. Moreover, a possible role of microglia in the
      interaction and recruitment of peripheral immune cells has so far been completely
      ignored. METHODS: We ablated microglia cells in 12-month-old WT and APP-PS1
      transgenic mice for 4 weeks using the CSF1R inhibitor PLX5622 and analyzed its
      consequences to AD pathology and in particular to peripheral immune cell
      infiltration. RESULTS: PLX5622 treatment successfully reduced microglia numbers.
      Interestingly, it uncovered a treatment-resistant macrophage population
      (Iba1+/TMEM119-). These cells strongly expressed the phagocytosis marker CD68 and
      the lymphocyte activation, homing, and adhesion molecule CD44, specifically at
      sites of amyloid-beta plaques in the brains of APP-PS1 mice. In consequence,
      ablation of microglia significantly raised the number of CD3+/CD8+ T-cells and
      reduced the expression of anti-inflammatory genes in the brains of APP-PS1 mice.
      CONCLUSION: We conclude that in neurodegenerative conditions, chronically
      activated microglia might limit CD3+/CD8+ T-cell recruitment to the brain and
      that local macrophages connect innate with adaptive immune responses.
      Investigating the role of peripheral immune cells, their interaction with
      microglia, and understanding the link between innate and adaptive immune
      responses in the brain might be a future directive in treating AD pathology.

PMID- 30241482
TI  - A loss-of-function mutation p.T52S in RIPPLY3 is a potential predisposing genetic
      risk factor for Chinese Han conotruncal heart defect patients without the 22q11.2
      deletion/duplication.
AB  - BACKGROUND: Conotruncal heart defect (CTD) is a complex congenital heart disease
      with a complex and poorly understood etiology. The transcriptional corepressor
      RIPPLY3 plays a pivotal role in heart development as a negative regulator of the
      key cardiac transcription factor TBX1. A previous study showed that RIPPLY3
      contribute to cardiac outflow tract development in mice, however, the
      relationship between RIPPLY3 and human cardiac malformation has not been
      reported. METHODS: 615 unrelated CTD Chinese Han patients were enrolled, we
      excluded the 22q11.2 deletion/duplication using a modified multiplex ligation
      dependent probe amplification method-CNVplex(r), and investigated the variants of
      RIPPLY3 in 577 patients without the 22q11.2 deletion/duplication by target
      sequencing. Functional assays were performed to testify the potential
      pathogenicity of nonsynonymous variants found in these CTD patients. RESULTS:
      Four rare heterozygous nonsynonymous variants (p.P30L, p.T52S, p.D113N and
      p.V179D) were identified in four CTD patients, the variant NM_018962.2:c.155C>G
      (p.T52S) is referred as rs745539198, and the variant NM_018962.2:c.337G>A
      (p.D113N) is referred as rs747419773. However, variants p.P30L and p.V179D were
      not found in multiple online human gene variation databases. Western blot
      analysis and immunofluorescence showed that there were no significant difference
      between wild type RIPPLY3 and these four variants. Luciferase assays revealed
      that the p.T52S variant altered the inhibition of TBX1 transcriptional activity
      in vitro, and co-immunoprecipitation assays showed that the p.T52S variant
      reduced the physical interaction of RIPPLY3 with TBX1. In addition to the results
      from pathogenicity prediction tools and evolutionary protein conservation, the
      p.T52S variant was thought to be a potentially deleterious variant. CONCLUSION:
      Our results provide evidence that deleterious variants in RIPPLY3 are potential
      molecular mechanisms involved in the pathogenesis of human CTD.

PMID- 30241483
TI  - An open-source tool to identify active travel from hip-worn accelerometer, GPS
      and GIS data.
AB  - BACKGROUND: Increases in physical activity through active travel have the
      potential to have large beneficial effects on populations, through both better
      health outcomes and reduced motorized traffic. However accurately identifying
      travel mode in large datasets is problematic. Here we provide an open source tool
      to quantify time spent stationary and in four travel modes(walking, cycling,
      train, motorised vehicle) from accelerometer measured physical activity data,
      combined with GPS and GIS data. METHODS: The Examining Neighbourhood Activities
      in Built Living Environments in London study evaluates the effect of the built
      environment on health behaviours, including physical activity. Participants wore
      accelerometers and GPS receivers on the hip for 7 days. We time-matched
      accelerometer and GPS, and then extracted data from the commutes of 326 adult
      participants, using stated commute times and modes, which were manually checked
      to confirm stated travel mode. This yielded examples of five travel modes:
      walking, cycling, motorised vehicle, train and stationary. We used this example
      data to train a gradient boosted tree, a form of supervised machine learning
      algorithm, on each data point (131,537 points), rather than on journeys. Accuracy
      during training was assessed using five-fold cross-validation. We also manually
      identified the travel behaviour of both 21 participants from ENABLE London
      (402,749 points), and 10 participants from a separate study (STAMP-2, 210,936
      points), who were not included in the training data. We compared our predictions
      against this manual identification to further test accuracy and test
      generalisability. RESULTS: Applying the algorithm, we correctly identified travel
      mode 97.3% of the time in cross-validation (mean sensitivity 96.3%, mean active
      travel sensitivity 94.6%). We showed 96.0% agreement between manual
      identification and prediction of 21 individuals' travel modes (mean sensitivity
      92.3%, mean active travel sensitivity 84.9%) and 96.5% agreement between the
      STAMP-2 study and predictions (mean sensitivity 85.5%, mean active travel
      sensitivity 78.9%). CONCLUSION: We present a generalizable tool that identifies
      time spent stationary and time spent walking with very high precision, time spent
      in trains or vehicles with good precision, and time spent cycling with moderate
      precisionIn studies where both accelerometer and GPS data are available this tool
      complements analyses of physical activity, showing whether differences in PA may
      be explained by differences in travel mode. All code necessary to replicate, fit
      and predict to other datasets is provided to facilitate use by other researchers.

PMID- 30241485
TI  - The path to great pediatric septic shock outcomes.

PMID- 30241481
TI  - The Pregnancy and Influenza Multinational Epidemiologic (PRIME) study: a
      prospective cohort study of the impact of influenza during pregnancy among women
      in middle-income countries.
AB  - BACKGROUND: The World Health Organization identifies pregnant women as at high
      risk for severe influenza, but influenza vaccines are underutilized among
      pregnant women. Data on influenza burden during pregnancy are largely limited to
      high-income countries and data on the impact of influenza on birth and perinatal
      outcomes are scarce. METHODS/DESIGN: This prospective, longitudinal cohort study
      of pregnant women in middle-income countries is designed to address three primary
      objectives: 1) to evaluate the effect of laboratory-confirmed influenza during
      pregnancy on pregnancy and perinatal outcomes; 2) to estimate the incidences of
      all-cause acute respiratory illness and laboratory-confirmed influenza during
      pregnancy; and 3) to examine the clinical spectrum of illness associated with
      influenza viruses. Through a multi-country network approach, three sites aim to
      enroll cohorts of 1500-3000 pregnant women just before local influenza seasons.
      Women aged >= 18 years with expected delivery dates >= 8 weeks after the start of
      the influenza season are eligible. Women are followed throughout pregnancy
      through twice weekly surveillance for influenza symptoms (>= 1 of myalgia, cough,
      runny nose, sore throat, or difficulty breathing) and have mid-turbinate nasal
      swabs collected for influenza virus testing during illness episodes. Primary
      outcomes include relative risk of preterm birth and mean birth weight among term
      singleton infants of women with and without reverse transcription polymerase
      chain reaction-confirmed influenza during pregnancy. Gestational age is
      determined by ultrasound at < 28 weeks gestation and birth weight is measured by
      digital scales using standardized methods. Sites are primarily urban in Bangkok,
      Thailand; Lima, Peru; and Nagpur, India. All sites recruit from antenatal clinics
      at referral hospitals and conduct surveillance using telephone calls, messaging
      applications, or home visits. Nasal swabs are self-collected by participants in
      Thailand and by study staff in Peru and India. During the first year (2017),
      sites enrolled participants during March-May in Peru and May-July in India and
      Thailand; 4779 women were enrolled. DISCUSSION: This study aims to generate
      evidence of the impact of influenza during pregnancy to inform decisions by
      Ministries of Health, healthcare providers, and pregnant women in middle-income
      countries about the value of influenza vaccination during pregnancy.

PMID- 30241484
TI  - Uncovering the mechanisms of research capacity development in health and social
      care: a realist synthesis.
AB  - BACKGROUND: Research capacity development (RCD) is considered fundamental to
      closing the evidence-practice gap, thereby contributing to health, wealth and
      knowledge for practice. Numerous frameworks and models have been proposed for
      RCD, but there is little evidence of what works for whom and under what
      circumstances. There is a need to identify mechanisms by which candidate
      interventions or clusters of interventions might achieve RCD and contribute to
      societal impact, thereby proving meaningful to stakeholders. METHODS: A realist
      synthesis was used to develop programme theories for RCD. Structured database
      searches were conducted across seven databases to identify papers examining RCD
      in a health or social care context (1998-2013). In addition, citation searches
      for 10 key articles (citation pearls) were conducted across Google Scholar and
      Web of Science. Of 214 included articles, 116 reported on specific interventions
      or initiatives or their evaluation. The remaining 98 articles were discussion
      papers or explicitly sought to make a theoretical contribution. A core set of 36
      RCD theoretical and conceptual papers were selected and analysed to generate
      mechanisms that map across macro contexts (individual, team, organisational,
      network). Data were extracted by means of 'If-Then' statements into an Excel
      spreadsheet. Models and frameworks were deconstructed into their original
      elements. RESULTS: Eight overarching programme theories were identified featuring
      mechanisms that were triggered across multiple contexts. Three of these fulfilled
      a symbolic role in signalling the importance of RCD (e.g. positive role models,
      signal importance, make a difference), whilst the remainder were more functional
      (e.g. liberate talents, release resource, exceed sum of parts, learning by doing
      and co-production of knowledge). Outcomes from one mechanism produced changes in
      context to stimulate mechanisms in other activities. The eight programme theories
      were validated with findings from 10 systematic reviews (2014-2017). CONCLUSIONS:
      This realist synthesis is the starting point for constructing an RCD framework
      shaped by these programme theories. Future work is required to further test and
      refine these findings against empirical data from intervention studies.

PMID- 30241486
TI  - BayesCCE: a Bayesian framework for estimating cell-type composition from DNA
      methylation without the need for methylation reference.
AB  - We introduce a Bayesian semi-supervised method for estimating cell counts from
      DNA methylation by leveraging an easily obtainable prior knowledge on the cell
      type composition distribution of the studied tissue. We show mathematically and
      empirically that alternative methods which attempt to infer cell counts without
      methylation reference only capture linear combinations of cell counts rather than
      provide one component per cell type. Our approach allows the construction of
      components such that each component corresponds to a single cell type, and
      provides a new opportunity to investigate cell compositions in genomic studies of
      tissues for which it was not possible before.

PMID- 30241489
TI  - A longitudinal review of national HIV policy and progress made in health facility
      implementation in Eastern Zimbabwe.
AB  - BACKGROUND: In recent years, WHO has made major changes to its guidance on the
      provision of HIV care and treatment services. We conducted a longitudinal study
      from 2013 to 2015 to establish how these changes have been translated into
      national policy in Zimbabwe and to measure progress in implementation within
      local health facilities. METHODS: National HIV programme policy guidelines
      published between 2003 and 2013 (n = 9) and 2014 and 2015 (n = 5) were reviewed
      to assess adoption of WHO recommendations on HIV testing services, prevention of
      mother-to-child transmission (PMTCT) of HIV, and provision of antiretroviral
      therapy (ART). Changes in local implementation of these policies over time were
      measured in two rounds of a survey conducted at 36 health facilities in Eastern
      Zimbabwe in 2013 and 2015. RESULTS: High levels of adoption of WHO guidance into
      national policy were recorded, including adoption of new recommendations made in
      2013-2015 to introduce PMTCT Option B+ and to increase the threshold for ART
      initiation from CD4 <= 350 cells/mm3 to <= 500 cells/mm3. New strategies to
      implement national HIV policies were introduced such as the decentralisation of
      ART services from hospitals to clinics and task-shifting of care from doctors to
      nurses. The proportions of health facilities offering free HIV testing and
      counselling, PMTCT (including Option B+) and ART services increased substantially
      from 2013 to 2015, despite reductions in numbers of health workers. Provision of
      provider-initiated HIV testing remained consistently high. At least one test-kit
      stock-out in the prior year was reported in most facilities (2013: 69%; 2015:
      61%; p = 0.44). Stock-outs of first-line ART and prophylactic drugs for
      opportunistic infections remained low. Repeat testing for HIV-negative
      individuals within 3 months decreased (2013: 97%; 2015: 72%; p = 0.01).
      Laboratory testing remained low across both survey rounds, despite policy and
      operational guidelines to expand coverage of diagnostic services. CONCLUSIONS:
      Good progress has been made in implementing international guidance on HIV service
      delivery in Zimbabwe. Further novel implementation strategies may be needed to
      achieve the latest targets for universal ART eligibility.

PMID- 30241488
TI  - Endotracheal tube-mounted camera-assisted intubation versus conventional
      intubation in intensive care: a prospective, randomised trial (VivaITN).
AB  - BACKGROUND: For critically ill patients, effective airway management with a high
      first-attempt success rate for endotracheal intubation is essential to prevent
      hypoxic complications during securing of the airway. Video guidance may improve
      first-attempt success rate over direct laryngoscopy (DL). METHODS: With ethics
      approval, this randomised controlled trial involved 54 critically ill patients
      who received endotracheal intubation using a tube with an integrated video camera
      (VivaSightTM-SL tube, VST, ETView Ltd., Misgav, Israel) or using conventional
      intubation under DL. RESULTS: The two groups did not differ in terms of
      intubation conditions. The first-attempt success rate was VST 96% vs. DL 93% (not
      statistically significant (n. s.)). When intubation at first attempt failed, it
      was successful in the second attempt in all patients. There was no difference in
      the median average time to intubation (VST 34 s (interquartile range 28-39) vs.
      DL 35 s (28-40), n. s.). Neither vomiting nor aspiration or accidental
      oesophageal intubation were observed in either group. The lowest pulsoxymetric
      oxygen saturation for VST was 96 (82-99) % vs. 99 (95-100) % for DL (n. s.).
      Hypotension defined as systolic blood pressure < 70 mmHg occurred in the VST
      group at 20% vs. the DL group at 15% (n. s.). CONCLUSION: In this pilot study, no
      advantage was shown for the VST. The VST should be examined further to identify
      patient groups that could benefit from intubation with the VST, that is, patients
      with difficult airway conditions. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02837055 . Registered on 13 June 2016.

PMID- 30241491
TI  - Is protein intake saturated at doses recommended by the feeding guidelines for
      critically ill patients?

PMID- 30241492
TI  - Extracorporeal membrane oxygenation offers long-term survival in childhood
      leukemia and acute respiratory failure.

PMID- 30241490
TI  - The association of clinical frailty with outcomes of patients reviewed by rapid
      response teams: an international prospective observational cohort study.
AB  - BACKGROUND: Frailty is a state of vulnerability to poor resolution of homeostasis
      after a stressor event and is strongly associated with adverse outcomes.
      Therefore, the assessment of frailty may be an essential part of evaluation in
      any healthcare encounter that might result in an escalation of care. The purpose
      of the study was to assess the frequency and association of frailty with clinical
      outcomes in patients subject to rapid response team (RRT) review. METHODS: In
      this multi-national prospective observational cohort study, centres with existing
      RRTs collected data over a 7-day period, with follow up of all patients at 24 h
      following their RRT call and at hospital discharge or 30 days following the event
      trigger (whichever came sooner). Investigators also collected data on the
      triggers and interventions provided and a bedside assessment on the level of
      patients' frailty using a clinical frailty scale. RESULTS: Amongst 1133 patients,
      40% were screened as frail, which was associated with older age (p < 0.001),
      admission under a medical speciality (p < 0.001), increased severity of illness
      at the time of the RRT review (p = 0.0047), and substantially higher frequency of
      limitations of care (p < 0.001). Importantly, 72% of patients screened as frail
      were either dead or dependent on hospital care by 30 days (p < 0.001). In the
      multivariable analysis, the significant risk factors for the composite endpoint
      "poor recovery" (died or were hospital-dependent by 30 days) were age (odds ratio
      (OR), 1.04; 95% confidence interval (CI), 1.03-1.05; p < 0.001), frailty level (p
      < 0.001), existing limitation of care (OR, 2.0; 95% CI, 1.3-3.0; p < 0.001), and
      the quick sequential organ failure assessment (qSOFA) score (p < 0.001).
      CONCLUSIONS: Higher frailty scores were associated with increased mortality and
      dependence on health care at 30 days. Our results indicate that frailty has an
      influence on the clinical trajectory of deteriorating patients and that such
      assessment should be included in discussion of goals and expectations of care.
      TRIAL REGISTRATION: Netherlands Trial Registry, NTR5535 . Registered on 23
      December 2015.

PMID- 30241494
TI  - Predictive values of the selected inflammatory index in elderly patients with
      papillary thyroid cancer.
AB  - BACKGROUND: The American Joint Committee on Cancer has recently revised the tumor
      node-metastasis (TNM) staging system on thyroid cancer, which illustrated that
      the cut-off age for predicting mortality has elevated from 45 to 55 years old. We
      aimed to investigate the inflammation index based on hematological parameters to
      predict the clinical characteristics of elderly papillary thyroid cancer (PTC)
      patients with an inferior prognosis. METHODS: We retrospectively analyzed 558
      patients newly diagnosed with PTC from January 2013 to December 2017, and 82 out
      of the 558 patients were over 55 years old. Receiver operating characteristic
      (ROC) study and univariate and multivariate logistic analysis was conducted to
      evaluate the diagnostic value of these preoperative inflammation indexes in PTC
      patients >= 55 years of age. RESULTS: Elevated neutrophils were prognostic of
      bilaterality (area under the ROC curve (AUC) = 0.673, p = 0.023) and lymph node
      metastasis (AUC = 0.649, p = 0.020). Decreased mean platelet volume (MPV) and
      platelet distribution width (PDW) were prognostic of coexistence with Hashimoto's
      thyroiditis (AUC = 0.736, p = 0.016; AUC = 0.721, p = 0.024). Elevated lymphocyte
      and lymphocyte-to-monocyte ratio (LMR) were prognostic of advanced TNM stage (AUC
      = 0.691, p = 0.029; AUC = 0.680, p = 0.040). Meanwhile, the logistic regression
      model further revealed that LMR >= 5.45 was an independent risk factor for the
      advanced TNM stage (odds ratio (OR) = 7.306, p = 0.036). CONCLUSIONS: The
      preoperative neutrophils, lymphocytes, MPV, PDW, LMR were all prognostic. More
      importantly, the increased in LMR independently contributed to the advanced TNM
      stage of PTC patients >= 55 years.

PMID- 30241487
TI  - Genomic approaches for studying crop evolution.
AB  - Understanding how crop plants evolved from their wild relatives and spread around
      the world can inform about the origins of agriculture. Here, we review how the
      rapid development of genomic resources and tools has made it possible to conduct
      genetic mapping and population genetic studies to unravel the molecular
      underpinnings of domestication and crop evolution in diverse crop species. We
      propose three future avenues for the study of crop evolution: establishment of
      high-quality reference genomes for crops and their wild relatives; genomic
      characterization of germplasm collections; and the adoption of novel
      methodologies such as archaeogenetics, epigenomics, and genome editing.

PMID- 30241493
TI  - Epidemiology of non-steroidal anti-inflammatory drugs consumption in Spain. The
      MCC-Spain study.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used
      despite their risk of gastrointestinal bleeding or cardiovascular events. We
      report the profile of people taking NSAIDs in Spain, and we include demographic
      factors, health-related behaviours and cardiovascular disease history. METHODS:
      Four thousand sixtyparticipants were selected using a pseudorandom number list
      from Family Practice lists in 12 Spanish provinces. They completed a face-to-face
      computerized interview on their NSAID consumption, demographic characteristics,
      body mass index, alcohol and tobacco consumption and medical history. In
      addition, participants completed a self-administered food-frequency and alcohol
      consumption questionnaire. Factors associated with ever and current NSAID
      consumption were identified by logistic regression. RESULTS: Women consumed more
      non-aspirin NSAIDs (38.8% [36.7-41.0]) than men (22.3 [20.5-24.2]), but men
      consumed more aspirin (11.7% [10.3-13.2]) than women (5.2% [4.3-6.3]).
      Consumption of non-aspirin NSAIDs decrease with age from 44.2% (39.4-49.1) in
      younger than 45 to 21.1% (18.3-24.2) in older than 75, but the age-pattern for
      aspirin usage was the opposite. Aspirin was reported by about 11% patients, as
      being twice as used in men (11.7%) than in women (5.2%); its consumption
      increased with age from 1.7% (< 45 years old) to 12.4% (>=75 years old). Aspirin
      was strongly associated with the presence of cardiovascular risk factors or
      established cardiovascular disease, reaching odds ratios of 15.2 (7.4-31.2) in
      women with acute coronary syndrome, 13.3 (6.2-28.3) in women with strokes and
      11.1 (7.8-15.9) in men with acute coronary syndrome. Participants with
      cardiovascular risk factors or diseases consumed as much non-aspirin NSAID as
      participants without such conditions. CONCLUSIONS: Non-aspirin NSAIDs were more
      consumed by women and aspirin by men. The age patterns of aspirin and non-aspirin
      NSAIDs were opposite: the higher the age, the lower the non-aspirin NSAIDs usage
      and the higher the aspirin consumption. People with cardiovascular risk factors
      or diseases consumed more aspirin, but they did not decrease their non-aspirin
      NSAIDs usage.

PMID- 30241496
TI  - A comparative analysis of library prep approaches for sequencing low input
      translatome samples.
AB  - BACKGROUND: Cell type-specific ribosome-pulldown has become an increasingly
      popular method for analysis of gene expression. It allows for expression analysis
      from intact tissues and monitoring of protein synthesis in vivo. However, while
      its utility has been assessed, technical aspects related to sequencing of these
      samples, often starting with a smaller amount of RNA, have not been reported. In
      this study, we evaluated the performance of five library prep protocols for
      ribosome-associated mRNAs when only 250 pg-4 ng of total RNA are used. RESULTS:
      We obtained total and RiboTag-IP RNA, in three biological replicates. We compared
      5 methods of library preparation for Illumina Next Generation sequencing: NuGEN
      Ovation RNA-Seq system V2 Kit, TaKaRa SMARTer Stranded Total RNA-Seq Kit, TaKaRa
      SMART-Seq v4 Ultra Low Input RNA Kit, Illumina TruSeq RNA Library Prep Kit v2 and
      NEBNext(r) UltraTM Directional RNA Library Prep Kit using slightly modified
      protocols each with 4 ng of total RNA. An additional set of samples was processed
      using the TruSeq kit with 70 ng, as a 'gold standard' control and the SMART-Seq
      v4 with 250 pg of total RNA. TruSeq-processed samples had the best metrics
      overall, with similar results for the 4 ng and 70 ng samples. The results of the
      SMART-Seq v4 processed samples were similar to TruSeq (Spearman correlation >
      0.8) despite using lower amount of input RNA. All RiboTag-IP samples had an
      increase in the intronic reads compared with the corresponding whole tissue,
      suggesting that the IP captures some immature mRNAs. The SMARTer-processed
      samples had a higher representation of ribosomal and non-coding RNAs leading to
      lower representation of protein coding mRNA. The enrichment or depletion of IP
      samples compared to corresponding input RNA was similar across all kits except
      for SMARTer kit. CONCLUSION: RiboTag-seq can be performed successfully with as
      little as 250 pg of total RNA when using the SMART-Seq v4 kit and 4 ng when using
      the modified protocols of other library preparation kits. The SMART-Seq v4 and
      TruSeq kits resulted in the highest quality libraries. RiboTag IP RNA contains
      some immature transcripts.

PMID- 30241495
TI  - Genes reveal traces of common recent demographic history for most of the Uralic
      speaking populations.
AB  - BACKGROUND: The genetic origins of Uralic speakers from across a vast territory
      in the temperate zone of North Eurasia have remained elusive. Previous studies
      have shown contrasting proportions of Eastern and Western Eurasian ancestry in
      their mitochondrial and Y chromosomal gene pools. While the maternal lineages
      reflect by and large the geographic background of a given Uralic-speaking
      population, the frequency of Y chromosomes of Eastern Eurasian origin is
      distinctively high among European Uralic speakers. The autosomal variation of
      Uralic speakers, however, has not yet been studied comprehensively. RESULTS:
      Here, we present a genome-wide analysis of 15 Uralic-speaking populations which
      cover all main groups of the linguistic family. We show that contemporary Uralic
      speakers are genetically very similar to their local geographical neighbours.
      However, when studying relationships among geographically distant populations, we
      find that most of the Uralic speakers and some of their neighbours share a
      genetic component of possibly Siberian origin. Additionally, we show that most
      Uralic speakers share significantly more genomic segments identity-by-descent
      with each other than with geographically equidistant speakers of other languages.
      We find that correlated genome-wide genetic and lexical distances among Uralic
      speakers suggest co-dispersion of genes and languages. Yet, we do not find long
      range genetic ties between Estonians and Hungarians with their linguistic sisters
      that would distinguish them from their non-Uralic-speaking neighbours.
      CONCLUSIONS: We show that most Uralic speakers share a distinct ancestry
      component of likely Siberian origin, which suggests that the spread of Uralic
      languages involved at least some demic component.

PMID- 30241497
TI  - Differential genetic responses to the stress revealed the mutation-order adaptive
      divergence between two sympatric ginger species.
AB  - BACKGROUND: Divergent genetic responses to the same environmental pressures may
      lead sympatric ecological speciation possible. Such speciation process possibly
      explains rapid sympatric speciation of island species. Two island endemic ginger
      species Zingiber kawagoii and Z. shuanglongensis was suggested to be
      independently originated from inland ancestors, but their island endemism and
      similar morphologies and habitats lead another hypothesis of in situ ecological
      speciation. For understanding when and how these two species diverged,
      intraspecific variation was estimated from three chloroplast DNA fragments
      (cpDNA) and interspecific genome-wide SNPs and expression differences after
      saline treatment were examined by transcriptomic analyses. RESULTS: Extremely low
      intraspecific genetic variation was estimated by cpDNA sequences in both species:
      nucleotide diversity pi = 0.00002 in Z. kawagoii and no nucleotide substitution
      but only indels found in Z. shuanglongensis. Nonsignificant inter-population
      genetic differentiation suggests homogenized genetic variation within species.
      Based on 53,683 SNPs from 13,842 polymorphic transcripts, in which 10,693 SNPs
      are fixed between species, Z. kawagoii and Z. shuanglongensis were estimated to
      be diverged since 218~ 238 thousand generations ago (complete divergence since
      41.5~ 43.5 thousand generations ago). This time is more recent than the time of
      Taiwan Island formation. In addition, high proportion of differential expression
      genes (DEGs) is non-polymorphic or non-positively selected, suggesting key roles
      of plastic genetic divergence in broaden the selectability in incipient
      speciation. While some positive selected DEGs were mainly the biotic and abiotic
      stress-resistance genes, emphasizing the importance of adaptive divergence of
      stress-related genes in sympatric ecological speciation. Furthermore, the higher
      proportional expression of functional classes in Z. kawagoii than in Z.
      shuanglongensis explains the more widespread distribution of Z. kawagoii in
      Taiwan. CONCLUSIONS: Our results contradict the previous hypothesis of
      independent origination of these two island endemic ginger species from SE China
      and SW China. Adaptive divergent responses to the stress explain how these
      gingers maintain genetic differentiation in sympatry. However, the recent
      speciation and rapid expansion make extremely low intraspecific genetic variation
      in these two species. This study arise a more probable speciation hypothesis of
      sympatric speciation within an island via the mutation-order mechanism underlying
      the same environmental pressure.

PMID- 30241498
TI  - Association between unhygienic menstrual management practices and prevalence of
      lower reproductive tract infections: a hospital-based cross-sectional study in
      Odisha, India.
AB  - BACKGROUND: The extent to which reproductive tract infections (RTIs) are
      associated with poor menstrual hygiene management (MHM) practices has not been
      extensively studied. We aimed to determine whether poor menstrual hygiene
      practices were associated with three common infections of the lower reproductive
      tract; Bacterial vaginosis (BV), Candida, and Trichomonas vaginalis (TV).
      METHODS: Non-pregnant women of reproductive age (18-45 years) and attending one
      of two hospitals in Odisha, India, between April 2015 and February 2016 were
      recruited for the study. A standardized questionnaire was used to collect
      information on: MHM practices, clinical symptoms for the three infections, and
      socio-economic and demographic information. Specimens from posterior vaginal
      fornix were collected using swabs for diagnosis of BV, Candida and TV infection.
      RESULTS: A total of 558 women were recruited for the study of whom 62.4% were
      diagnosed with at least one of the three tested infections and 52% presented with
      one or more RTI symptoms. BV was the most prevalent infection (41%), followed by
      Candida infection (34%) and TV infection (5.6%). After adjustment for potentially
      confounding factors, women diagnosed with Candida infection were more likely to
      use reusable absorbent material (aPRR = 1.54, 95%CI 1.2-2.0) and practice lower
      frequency of personal washing (aPRR = 1.34, 95%CI 1.07-1.7). Women with BV were
      more likely to practice personal washing less frequently (aPRR = 1.25, 95%CI 1.0
      1.5), change absorbent material outside a toilet facility (aPRR = 1.21, 95%CI 1.0
      1.48) whilst a higher frequency of absorbent material changing was protective
      (aPRR = 0.56, 95%CI 0.4-0.75). No studied factors were found to be associated
      with TV infection. In addition, among women reusing absorbent material, Candida
      but not BV or TV - infection was more frequent who dried their pads inside their
      houses and who stored the cloth hidden in the toilet compartment. CONCLUSION: The
      results of our study add to growing number of studies which demonstrate a strong
      and consistent association between poor menstrual hygiene practices and higher
      prevalence of lower RTIs.

PMID- 30241499
TI  - Long-term, telephone-based follow-up after stroke and TIA improves risk factors:
      36-month results from the randomized controlled NAILED stroke risk factor trial.
AB  - BACKGROUND: Strategies are needed to improve adherence to the blood pressure (BP)
      and low-density lipoprotein cholesterol (LDL-C) level recommendations after
      stroke and transient ischemic attack (TIA). We investigated whether nurse-led,
      telephone-based follow-up that included medication titration was more efficient
      than usual care in improving BP and LDL-C levels 36 months after discharge
      following stroke or TIA. METHODS: All patients admitted for stroke or TIA at
      Ostersund hospital that could participate in the telephone-based follow-up were
      considered eligible. Participants were randomized to either nurse-led, telephone
      based follow-up (intervention) or usual care (control). BP and LDL-C were
      measured one month after discharge and yearly thereafter. Intervention group
      patients who did not meet the target values received additional follow-up,
      including lifestyle counselling and medication titration, to reach their
      treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L). The primary outcome was
      the systolic BP level 36 months after discharge. RESULTS: Out of 871 randomized
      patients, 660 completed the 36-month follow-up. The mean systolic and diastolic
      BP values in the intervention group were 128.1 mmHg (95% CI 125.8-130.5) and 75.3
      mmHg (95% CI 73.8-76.9), respectively. This was 6.1 mmHg (95% CI 3.6-8.6, p <
      0.001) and 3.4 mmHg (95% CI 1.8-5.1, p < 0.001) lower than in the control group.
      The mean LDL-C level was 2.2 mmol/L in the intervention group, which was 0.3
      mmol/L (95% CI 0.2-0.5, p < 0.001) lower than in controls. A larger proportion of
      the intervention group reached the treatment goal for BP (systolic: 79.4% vs.
      55.3%, p < 0.001; diastolic: 90.3% vs. 77.9%, p < 0.001) as well as for LDL-C
      (69.3% vs. 48.9%, p < 0.001). CONCLUSIONS: Compared with usual care, a nurse-led
      telephone-based intervention that included medication titration after stroke or
      TIA improved BP and LDL-C levels and increased the proportion of patients that
      reached the treatment target 36 months after discharge. TRIAL REGISTRATION:
      ISRCTN Registry ISRCTN23868518 (retrospectively registered, June 19, 2012).

PMID- 30241500
TI  - Transcriptional profiling of liver during the critical embryo-to-hatchling
      transition period in the chicken (Gallus gallus).
AB  - BACKGROUND: Although hatching is perhaps the most abrupt and profound metabolic
      challenge that a chicken must undergo; there have been no attempts to
      functionally map the metabolic pathways induced in liver during the embryo-to
      hatchling transition. Furthermore, we know very little about the metabolic and
      regulatory factors that regulate lipid metabolism in late embryos or newly
      hatched chicks. In the present study, we examined hepatic transcriptomes of 12
      embryos and 12 hatchling chicks during the peri-hatch period-or the metabolic
      switch from chorioallantoic to pulmonary respiration. RESULTS: Initial
      hierarchical clustering revealed two distinct, albeit opposing, patterns of
      hepatic gene expression. Cluster A genes are largely lipolytic and highly
      expressed in embryos. While, Cluster B genes are lipogenic/thermogenic and mainly
      controlled by the lipogenic transcription factor THRSPA. Using pairwise
      comparisons of embryo and hatchling ages, we found 1272 genes that were
      differentially expressed between embryos and hatchling chicks, including 24
      transcription factors and 284 genes that regulate lipid metabolism. The three
      most differentially-expressed transcripts found in liver of embryos were MOGAT1,
      DIO3 and PDK4, whereas THRSPA, FASN and DIO2 were highest in hatchlings. An
      unusual finding was the "ectopic" and extremely high differentially expression of
      seven feather keratin transcripts in liver of 16 day embryos, which coincides
      with engorgement of liver with yolk lipids. Gene interaction networks show
      several transcription factors, transcriptional co-activators/co-inhibitors and
      their downstream genes that exert a 'ying-yang' action on lipid metabolism during
      the embryo-to-hatching transition. These upstream regulators include ligand
      activated transcription factors, sirtuins and Kruppel-like factors. CONCLUSIONS:
      Our genome-wide transcriptional analysis has greatly expanded the hepatic
      repertoire of regulatory and metabolic genes involved in the embryo-to-hatchling
      transition. New knowledge was gained on interactive transcriptional networks and
      metabolic pathways that enable the abrupt switch from ectothermy (embryo) to
      endothermy (hatchling) in the chicken. Several transcription factors and their
      coactivators/co-inhibitors appear to exert opposing actions on lipid metabolism,
      leading to the predominance of lipolysis in embryos and lipogenesis in
      hatchlings. Our analysis of hepatic transcriptomes has enabled discovery of
      opposing, interconnected and interdependent transcriptional regulators that
      provide precise ying-yang or homeorhetic regulation of lipid metabolism during
      the critical embryo-to-hatchling transition.

PMID- 30241501
TI  - A genome-wide association study for natural antibodies measured in blood of
      Canadian Holstein cows.
AB  - BACKGROUND: Natural antibodies (NAb) are an important component of the innate
      immune system, and fight infections as a part of the first line defence. NAb are
      poly-reactive and can respond non-specifically to antigens. Therefore, NAb may be
      a key trait when evaluating an animal's potential natural disease resistance.
      Variation in NAb is caused by both genetic and environmental factors. In this
      study genetic parameters of NAb were estimated and a genome-wide association
      study (GWAS) was performed to gain further understanding on the genes that are
      responsible for the observed genetic variation of NAb in Canadian Holsteins.
      RESULTS: In total, blood samples of 1327 cows from 64 farms were studied. NAb
      binding to keyhole limpet hemocyanin (KLH) were determined via indirect ELISA.
      Immunoglobulin (Ig) isotypes, IgG and IgM, were evaluated. From the sample
      population, 925 cows were genotyped for 45,187 markers and each individual marker
      was tested to detect genetic variation in NAb levels. The relationships among
      animals was accounted for with genomic relationship. Results show heritabilities
      of 0.27 +/- 0.064 (IgG) and 0.31 +/- 0.065 (IgM). In total, 23 SNPs were found to
      be associated with IgG, but no SNPs were associated with IgM (FDR p-value <
      0.05). The significant SNPs were located on autosomal chromosomes 1, 20 and 21 of
      the cow genome. Functional annotation analysis of the positional candidate genes
      revealed two sets of genes with biologically relevant functions related to NAb.
      In one set, seven genes with crucial roles in the production of antibody in B
      cells were associated with the trafficking of vesicles inside the cells between
      organelles. In the second set, two genes among positional candidate genes were
      associated with isotype class-switching and somatic hypermutation of B cells.
      CONCLUSIONS: This study demonstrated the possibility of increasing NAb through
      selective breeding. In addition, the effects of two candidate pathways are
      proposed for further investigation of NAb production in Holsteins.

PMID- 30241502
TI  - Anti-inflammatory effects of minocycline are mediated by retinoid signaling.
AB  - BACKGROUND: Minocycline is a lipophilic tetracycline of increasing appeal in
      neuroscience as it inhibits microglial activation, a mechanism involved in
      numerous neuropsychiatric disorders. Own data point towards retinoid-mediated
      effects of minocycline in murine brain and skin, and towards a vicious cycle of
      neuroinflammation which is driven by microglial activation-induced breakdown of
      local retinoids such as retinoic acid (RA). We therefore sought to study
      minocycline's anti-inflammatory effects on human microglial-like monocyte-derived
      cells in the context of retinoid signaling. RESULTS: As hypothesized, minocycline
      exposure resulted in a substantial increase of RA levels in the human monocytic
      cell line THP-1. While pro-inflammatory stimulation with lipopolysaccharides
      resulted in increased tryptophane-degrading indoleamine-2,3-dioxygenase IDO
      expression and TNF-alpha levels in primary human monocyte-derived microglial-like
      cells, this effect was attenuated by minocycline only in the presence of
      retinoids. The anti-inflammatory effects of minocycline on TNF-alpha expression
      were completely abolished by a pharmacological blockage of retinoic acid
      receptors (RARs) using BMS-493 and unaffected by selectively blocking retinoid-X
      receptors using UVI-3003. CONCLUSIONS: Our data indicate for the first time a RA
      dependent, anti-inflammatory effect for minocycline in human microglial-like
      cells via inhibition of local RA turnover. The RA-dependent mode of action for
      minocycline appears to be predominantly mediated through RAR-signaling.

PMID- 30241503
TI  - Seroprevalence of hepatitis B virus infection and associated factors among
      healthcare workers in northern Tanzania.
AB  - BACKGROUND: Hepatitis B virus infection is a global health problem with the
      highest prevalence in East Asia and Sub-Saharan Africa. The majority of infected
      people, including healthcare workers are unaware of their status. This study is
      aimed to determining seroprevalence of hepatitis B virus infection and associated
      factors among healthcare workers in northern Tanzania. METHODS: This cross
      sectional study included 442 healthcare workers (HCWs) from a tertiary and
      teaching hospital in Tanzania before the nationwide hepatitis B vaccination
      campaign in 2004. Questionnaire- based interviews were used to obtain detailed
      histories of the following: demographic characteristics; occupation risks such
      splash and needle stick injuries or other invasive procedure such as intravenous,
      intramuscular or subcutaneous injections; history of blood transfusion and
      surgeries, as well as HCWs'knowledge of HBV. Serological markers of HBV were done
      using Laborex HBsAg rapid test. Serology was done at zero months and repeated
      after six months ( bioscienceinternational.co.ke/rapid-test-laborex.html HBsAg
      Piazzale-milano-2, Italy [Accessed on November 2017]). Chi-square (chi2) tests
      were used to compare proportion of HBV infection by different HCWs
      characteristics. Multivariable logistic regression was used to determine factors
      associated with HBV infection. RESULTS: A total of 450 surveys were sent out,
      with a 98.2% response rate. Among the 442 HCWs who answered the questionnaire,
      the prevalence of chronic hepatitis B virus infection was 5.7% (25/442). Only 50
      (11.3%) of HCWs were aware of the HBV status. During the second HBsAg testing
      which was done after six months one participant sero-converted hence was
      excluded. Adjusted for other factors, history of blood transfusion significantly
      increased the odds of HBV infection (OR = 21.44, 95%CI 6.05, 76.01, p < 0.001)
      while HBV vaccine uptake was protective against HBV infection (OR = 0.06, 95%CI
      0.02, 0.26, p < 0.001). The majority of HCWs with chronic HBV infection had poor
      to fare knowledge about HBV infection but this was not statistically significant
      when controlled for confounding. CONCLUSIONS: Prevalence of HBV among health care
      workers was 5.7% which is similar to national prevalence. Although the response
      rate to take part in the study was good but knowledge on HBV infection among HCWs
      was unsatisfactory. History of blood transfusion increased risks while vaccine
      uptake decreased the risk of HBV infection. This study recommends continues
      vaccinating HCWs together with continues medical education all over the country.
      We also recommend documentation of vaccination evidence should be asked before
      employment of HCWs in order to sensitize more uptakes of vaccinations. Although
      we didn't assess the use of personal protective equipment but we encourage HCWs
      to abide strictly on universal protections against nosocomial infections.

PMID- 30241504
TI  - The effect of sodium nitrite infusion on renal function, brachial and central
      blood pressure during enzyme inhibition by allopurinol, enalapril or
      acetazolamide in healthy subjects: a randomized, double-blinded, placebo
      controlled, crossover study.
AB  - BACKGROUND: Sodium nitrite (NaNO2) causes vasodilation, presumably by enzymatic
      conversion to nitric oxide (NO). Several enzymes with nitrite reducing
      capabilities have been discovered in vitro, but their relative importance in vivo
      has not been investigated. We aimed to examine the effects of NaNO2 on blood
      pressure, fractional sodium excretion (FENa), free water clearance (CH2O) and
      GFR, after pre-inhibition of xanthine oxidase, carbonic anhydrase, and
      angiotensin-converting enzyme. The latter as an approach to upregulate
      endothelial NO synthase activity. METHODS: In a double-blinded, placebo
      controlled, crossover study, 16 healthy subjects were treated, in a randomized
      order, with placebo, allopurinol 150 mg twice daily (TD), enalapril 5 mg TD, or
      acetazolamide 250 mg TD. After 4 days of treatment and standardized diet, the
      subjects were examined at our lab. During intravenous infusion of 240 MUg
      NaNO2/kg/hour for 2 h, we measured changes in brachial and central blood pressure
      (BP), plasma cyclic guanosine monophosphate (P-cGMP), plasma and urine
      osmolality, GFR by 51Cr-EDTA clearance, FENa and urinary excretion rate of cGMP
      (U-cGMP) and nitrite and nitrate (U-NOx). Subjects were supine and orally water
      loaded throughout the examination day. RESULTS: Irrespective of pretreatment, we
      observed an increase in FENa, heart rate, U-NOx, and a decrease in CH2O and
      brachial systolic BP during NaNO2 infusion. P-cGMP and U-cGMP did not change
      during infusion. We observed a consistent trend towards a reduction in central
      systolic BP, which was only significant after allopurinol. CONCLUSION: This study
      showed a robust BP lowering, natriuretic and anti-aquaretic effect of intravenous
      NaNO2 regardless of preceding enzyme inhibition. None of the three enzyme
      inhibitors used convincingly modified the pharmacological effects of NaNO2. The
      steady cGMP indicates little or no conversion of nitrite to NO. Thus the effect
      of NaNO2 may not be mediated by NO generation. TRIAL REGISTRATION: EU Clinical
      Trials Register, 2013-003404-39 . Registered December 3 2013.

PMID- 30241507
TI  - Does social participation reduce the risk of functional disability among older
      adults in China? A survival analysis using the 2005-2011 waves of the CLHLS data.
AB  - BACKGROUND: Existing studies in developed countries show that social
      participation has beneficial effects on the functional ability of older adults,
      but research on Chinese older people is limited. This study examined the effects
      of participating in different types of social activities on the onset of
      functional disability and the underlying behavioral and psychosocial mechanisms
      among older adults aged 65 and older in China. METHODS: The 2005, 2008, and 2011
      waves of the Chinese Longitudinal Health Longevity Study were used. Life table
      analysis and discrete time hazard models were adopted to examine the relationship
      between social participation and functional disability. Social participation was
      defined as the frequencies of engaging in group leisure-time activities (i.e.,
      playing cards/mahjong) and organized social activities, involving in informal
      social interactions (i.e., number of siblings frequently visited), and
      participating in paid jobs. Extensive social participation was measured by a
      composite index by adding up the four types of social activities that an older
      person was engaged in. RESULTS: After controlling for the effect of socio
      demographic characteristics, health status, and health behavioral factors,
      extensive social participation is associated with a significant reduced risk for
      the onset of functional disability (hazard ratio [HR] = 0.92, p < 0.001).
      Different types of social participation affect the risk of functional decline
      through different mechanisms. Frequent playing of cards/mahjong is a protective
      factor for functional decline (HR = 0.78, p < 0.001), and the relationship is
      partially mediated by cognitive ability and positive emotions (accounting for
      18.9% and 7.0% of the association, respectively). Frequent participation in
      organized social activities is significantly related to a reduced risk of
      functional decline (HR = 0.78, p < 0.001), and the association is mediated by
      physical exercises and cognitive ability (accounting for 25.7% and 17.7% of the
      association, respectively). Frequent visits from siblings has a strong inverse
      relationship with functional decline (HR = 0.75, p < 0.001). However, no
      significant association between paid job and functional decline is observed.
      CONCLUSION: Extensive social participation, regular engagement in group leisure
      time activities, organized social activities, and informal social interactions in
      particular may have beneficial effects on the functional health of older adults
      through behavioral and psychosocial pathways. The findings shed light for the
      importance of promoting social participation among older adults.

PMID- 30241506
TI  - The estrogen receptor 1 gene affects bone mineral density and osteoporosis
      treatment efficiency in Slovak postmenopausal women.
AB  - BACKGROUND: The study investigated the associations of rs9340799:A > G (XbaI) and
      rs2234693:T > C (PvuII) polymorphisms in the estrogen receptor 1 gene (ESR1) with
      femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical
      markers of bone turnover, calcium and phosphate levels, fracture prevalence, and
      a response to two types of anti-osteoporotic therapy in postmenopausal women from
      southern Slovakia. METHODS: We analysed 343 postmenopausal Slovak women (62.40 +/
      0.46 years). The influence of rs9340799 (AA vs. AG + GG) and rs2234693 (TT vs.
      TC + CC) genotypes on BMD and biochemical markers was evaluated by covariance
      analysis adjusted for age and BMI. Binary logistic regression was used to
      evaluate the genotype effect on fracture prevalence. Pharmacogenetic part of the
      study included women who received a regular therapy of HT (17beta estradiol with
      progesterone; 1 mg/day for both; N = 76) or SERMs/raloxifene (60 mg/day; N = 64)
      during 48 months. The genotype-based BMD change was assessed by variance analysis
      for repeated measurements. RESULTS: Women with AA genotype of rs9340799 had
      higher BMD-FN (+ 0.12 +/- 0.57 of T-score) and BMD-LS (+ 0.17 +/- 0.08 of T
      score) in comparison with AG + GG. The rs2234693 polymorphism did not affect any
      of the monitored parameters. No effect of any ESR1 polymorphisms was found on
      fracture prevalence. Both types of anti-osteoporotic therapy had a positive
      effect on BMD improvement in FN and LS sites. Considering the effect of the ESR1
      gene within the HT, the subjects with rs9340799/AA genotype showed worse response
      than those with GG genotype (- 0.26 +/- 0.10 of BMD-FN T-score; - 0.35 +/- 0.10
      of BMD-LS T-score) and also with AG genotype (- 0.22 +/- 0.08 of BMD-LS T-score).
      The rs2234693/TT genotype responded poorer in BMD-LS in comparison with TC (-
      0.22 +/- 0.08 of T-score) and CC (- 0.35 +/- 0.09 of T-score). The effect of the
      ESR1 gene on raloxifene therapy was reported only in BMD-LS. Subjects with
      rs9340799/AA genotype had a - 0.30 +/- 0.11 of T-score worse response compared to
      AG genotype. The rs2234693/TT genotype showed - 0.39 +/- 0.11 and - 0.46 +/- 0.15
      lower T-scores in comparison with TC and CC genotypes, respectively. CONCLUSIONS:
      The rs9340799 polymorphism may contribute to decreased BMD in postmenopausal
      women from southern Slovakia; however, this is not related to higher fracture
      prevalence. Concurrently, both polymorphisms affected a response to analysed anti
      osteoporotic therapies.

PMID- 30241508
TI  - Urinary epidermal growth factor, monocyte chemoattractant protein-1 or their
      ratio as predictors for rapid loss of renal function in type 2 diabetic patients
      with diabetic kidney disease.
AB  - BACKGROUND: Increased monocyte chemoattractant protein-1 (MCP-1) and decreased
      epidermal growth factor (EGF) are promising biomarkers to predict progressive
      decline in kidney function in non-diabetic kidney diseases. We aimed to evaluate
      the performance of urinary EGF, MCP-1 or their ratio in predicting rapid decline
      of GFR in a cohort of Type 2 diabetic patients (T2DM) with diabetic kidney
      disease (DKD). METHODS: T2DM patients (n = 83) with DKD at high risk for renal
      progression were followed up prospectively. The baseline urine values of MCP-1 to
      creatinine ratio (UMCP-1), EGF to creatinine ratio (UEGF), EGF to MCP-1 ratio
      (UEGF/MCP-1) and albumin to creatinine ratio (UACR) were measured. The primary
      outcome was a decline in estimated glomerular filtration rate (GFR) of >=25%
      yearly from baseline. RESULTS: During follow-up time of 23 months, patients with
      rapid decline in estimated GFR of >=25% yearly from baseline had significantly
      higher baseline levels of UMCP-1, and UACR and lower UEGF and UEGF/MCP-1 ratio.
      All renal biomarkers predicted primary outcomes with ROC (95%CI) for UMCP-1=0.73
      (0.62-0.84), UEGF=0.68 (0.57-0.80), UEGF/MCP-1=0.74 (0.63-0.85), and UACR =0.84
      (0.75-0.93). By univariate analysis, blood pressure, GFR, UACR, UMCP-1, UEGF, and
      UEGF/MCP-1 were associated with rapid decline GFR. By multivariate analysis,
      UACR, systolic blood pressure, and UMCP-1 or UEGF/MCP-1 were independently
      associated with rapid GFR decline. CONCLUSIONS: UMCP-1 or UEGF/MCP-1 ratio were
      associated with rapid renal progression independent from conventional risk
      factors in DKD.

PMID- 30241505
TI  - Biomarkers: paving stones on the road towards the personalized precision medicine
      for oral squamous cell carcinoma.
AB  - Traditional therapeutics have encountered a bottleneck caused by diagnosis delay
      and subjective and unreliable assessment. Biomarkers can overcome this bottleneck
      and guide us toward personalized precision medicine for oral squamous cell
      carcinoma. To achieve this, it is important to efficiently and accurately screen
      out specific biomarkers from among the huge number of molecules. Progress in
      omics-based high-throughput technology has laid a solid foundation for biomarker
      discovery. With credible and systemic biomarker models, more precise and
      personalized diagnosis and assessment would be achieved and patients would be
      more likely to be cured and have a higher quality of life. However, this is not
      straightforward owing to the complexity of molecules involved in tumorigenesis.
      In this context, there is a need to focus on tumor heterogeneity and homogeneity,
      which are discussed in detail. In this review, we aim to provide an understanding
      of biomarker discovery and application for precision medicine of oral squamous
      cell carcinoma, and have a strong belief that biomarker will pave the road toward
      future precision medicine.

PMID- 30241509
TI  - Minimally invasive anterior muscle-sparing versus a transgluteal approach for
      hemiarthroplasty in femoral neck fractures-a prospective randomised controlled
      trial including 190 elderly patients.
AB  - BACKGROUND: The relevance of femoral neck fractures (FNFs) increases with the
      ageing of numerous societies, injury-related decline is observed in many
      patients. Treatment strategies have evolved towards primary joint replacement,
      but the impact of different approaches remains a matter of debate. The aim of
      this trial was to evaluate the benefit of an anterior minimally-invasive (AMIS)
      compared to a lateral Hardinge (LAT) approach for hemiarthroplasty in these
      oftentimes frail patients. METHODS: Four hundred thirty-nine patients were
      screened during the 44-months trial, aiming at the evaluation of 150 patients >
      60 yrs. of age. Eligible patients were randomised using an online-tool with
      completely random assignment. As primary endpoint, early mobility, a predictor
      for long-term outcomes, was evaluated at 3 weeks via the "Timed up and go" test
      (TUG). Secondary endpoints included the Functional Independence Measure (FIM),
      pain, complications, one-year mobility and mortality. RESULTS: A total of 190
      patients were randomised; both groups were comparable at baseline, with a
      predominance for frailty-associated factors in the AMIS-group. At 3 weeks, 146
      patients were assessed for the primary outcome. There was a reduction in the
      median duration of TUG performance of 21.5% (CI [- 41.2,4.7], p = 0.104) in the
      AMIS-arm (i.e., improved mobility). This reduction was more pronounced in
      patients with signs of frailty or cognitive impairment. FIM scores increased on
      average by 6.7 points (CI [0.5-12.8], p = 0.037), pain measured on a 10-point
      visual analogue scale decreased on average by 0.7 points (CI: [- 1.4,0.0], p =
      0.064). The requirement for blood transfusion was lower in the AMIS- group, the
      rate of complications comparable, with a higher rate of soft tissue complications
      in the LAT-group. The mortality was higher in the AMIS-group. CONCLUSION: These
      results, similar to previous reports, support the concept that in elderly
      patients at risk of frailty, the AMIS approach for hemiarthroplasty can be
      beneficial, since early mobilisation and pain reduction potentially reduce
      deconditioning, morbidity and loss of independence. The results are, however,
      influenced by a plethora of factors. Only improvements in every aspect of the
      therapeutic chain can lead to optimisation of treatment and improve outcomes in
      this growing patient population. TRIAL REGISTRATION: www.clinicaltrials.gov :
      NCT01408693 (registered August 3rd 2011).

PMID- 30241510
TI  - Immunogenicity of the CYD tetravalent dengue vaccine using an accelerated
      schedule: randomised phase II study in US adults.
AB  - BACKGROUND: The live attenuated tetravalent dengue vaccine (CYD-TDV) is licensed
      using a 0-, 6- and 12-month schedule in dengue-endemic areas. An effective
      shorter schedule may provide more rapid, optimal protection of targeted
      populations during vaccine campaigns in dengue-endemic countries. We compared
      immune responses to two schedules of CYD-TDV in a non-endemic population. We also
      evaluated the impact of yellow fever (YF) co-administration. METHODS: This phase
      II, open-label, multicentre study enrolled 390 healthy 18-45-year-olds in the USA
      with no prior exposure to dengue. Participants were randomised (4:4:4:1) to four
      treatment groups stratified by prior YF vaccine status: Group 1, CYD-TDV standard
      0-6-12 months schedule; Group 2, CYD-TDV accelerated 0-2-6 months schedule; Group
      3, CYD-TDV accelerated schedule with YF co-administered (dose 1); Group 4, YF
      vaccination only. Neutralising antibody geometric mean titres (GMTs) and
      percentages of seropositive participants (antibody titres >=10 [1/dil]) were
      measured against each dengue serotype using a 50% plaque reduction neutralisation
      test. RESULTS: On D28 post-CYD-TDV dose 3, there were no marked differences in
      seropositivity rates and GMTs between Groups 1 and 2. In Groups 1 and 2
      respectively, 73.4 and 82.4% were dengue seropositive for >=3 serotypes, with
      50.0 and 42.6% seropositive against all four serotypes. Flavivirus status (FV+ or
      FV-) at baseline did not markedly affect GMTs and seropositivity rates with
      either schedule. In Groups 1 and 2, GMTs measured 6 months after the third dose
      decreased against all serotypes, except for a small increase in GMT for serotype
      4 in Group 1. In addition, dengue seropositivity remained above 70% for serotypes
      2, 3 and 4 in Groups 1 and 2. Co-administration with YF did not affect antibody
      responses against dengue and YF or impact vaccine safety following completion of
      the compressed schedule, compared to dengue or YF vaccination alone. CONCLUSIONS:
      The live attenuated CYD-TDV vaccine given in a compressed schedule in a non
      endemic setting can elicit similar antibody responses to the licensed CYD-TDV
      schedule. TRIAL REGISTRATION: This trial was registered on cinicaltrials.gov,
      NCT01488890 (December 8, 2011).

PMID- 30241511
TI  - Health-related quality of life on tele-monitoring for users with pacemakers 6
      months after implant: the NORDLAND study, a randomized trial.
AB  - BACKGROUND: With an ageing population and widening indications for pacemakers
      implantation, the number of persons carrying an implant is steadily increasing.
      The routine follow-up is thus a heavy burden for the respective NHS as well as
      for the patients and their relatives. Most of them of the studies have been
      performed in densely populated areas and nearby to the hospital. It is thus
      unknown whether these results could be applied also in rural areas such as
      Northern Norway with a more scattered population. The aim of this study was to
      assess the effectiveness of tele-monitoring (TM) in patients with pacemakers
      regarding reliability, safety and health-related quality of life, compared to
      traditional follow-up in outpatient clinic in a setting where geographical
      effects could possible influence the results. METHODS: The NORDLAND study is a
      controlled, randomized, non-masked clinical trial in pacemaker patients, with
      data collection carried out during the pre-implant stage and after 6 months.
      Between August of 2014 and November of 2015, 50 patients were assigned to either
      a tele-monitoring group (n = 25) or a conventional hospital monitoring (HM) group
      (n = 25). The EuroQol-5D (EQ-5D) utilities and visual analogue scale (VAS) and
      the Minnesota Living with Heart Failure Questionnaire (MLHFQ) were used to
      measure Health-Related Quality of Life. Baseline characteristics and number of
      hospital visits were also analyzed. RESULTS: The baseline characteristics of the
      two study groups were similar for EQ-5D utilities (TM:0.81; HM:0.76; p = 0.47),
      EQ-5D VAS (TM: 64.00; HM:64.88; p = 0.86) and the MLHFQ (TM:20.20; HM:28.96; p =
      0.07). At the 6 month follow-up, there were no significant differences between
      the groups in EQ-5D utilities (TM: 0.81; HM: 0.76; p = 0.54) and EQ-5D VAS scores
      (TM: 72.71; HM: 59.79; p = 0.08). The MLHFQ score was improved in both groups
      (TM: -4.40; HM: -15.13; p <  0.001). The number of in-office visits was similar
      in both groups (TM: 1.24 vs HM: 1.12; P = 0.30). CONCLUSIONS: The NORDLAND trial
      shows that HRQoL is improved after implant in both groups. Without significant
      differences with regards to effectiveness and safety. In addition, provides a
      scientifically rigorous method to the field of HRQoL evaluations in patients with
      pacemakers. TRIAL REGISTRATION: ClinicalTrials.gov NCT02237404 , September 11,
      2014.

PMID- 30241512
TI  - Prediction of perioperative complications after robotic-assisted radical
      hysterectomy for cervical cancer using the modified surgical Apgar score.
AB  - BACKGROUND: Although there has been marked development in surgical techniques,
      there is no easy and fast method of predicting complications in minimally
      invasive surgeries. We evaluated whether the modified surgical Apgar score (MSAS)
      could predict perioperative complications in patients undergoing robotic-assisted
      radical hysterectomy. METHODS: All patients with cervical cancer undergoing
      robotic-assisted radical hysterectomy at our institution between January 2011 and
      May 2017 were included. Their clinical characteristics were retrieved from their
      medical records. The surgical Apgar score (SAS) was calculated from the estimated
      blood loss, lowest mean arterial pressure, and lowest heart rate during surgery.
      We modified the SAS considering the lesser blood loss typical of robotic
      surgeries. Perioperative complications were defined using a previous study and
      the Clavien-Dindo classification and subdivided into intraoperative and
      postoperative complications. We analyzed the association of perioperative
      complications with low MSAS. RESULTS: A total of 138 patients were divided into 2
      groups: with (n = 53) and without (n = 85) complications. According to the
      Clavien-Dindo classification, 49 perioperative complications were classified
      under Grade I (73.1%); 13, under Grade II (19.4%); and 5, under Grade III (7.5%);
      0, under both Grade IV and Grade V. Perioperative complications were
      significantly associated with surgical time (p = 0.026). The MSAS had a
      correlation with perioperative complications (p = 0.047). The low MSAS (MSAS,
      <=6; n = 52) group had significantly more complications [40 (76.9%), p = 0.01].
      Intraoperative complications were more correlated with a low MSAS than were
      postoperative complications [1 (1.2%) vs. 21 (40.4%); p < 0.001, 13 (15.1%) vs.
      25 (48.1%); p = 0.29, respectively]. We also analyzed the risk-stratified MSAS in
      3 subgroups: low (MSAS, 7-10), moderate (MSAS 5-6), and high risks (MSAS, 0-4).
      The prevalence of intraoperative complications significantly increased as the
      MSAS decreased p = 0.01). CONCLUSIONS: This study was consistent the concept that
      the intuitive and simple MSAS might be more useful in predicting intraoperative
      complications than in predicting postoperative complications in minimally
      invasive surgeries, such as robotic-assisted radical hysterectomy for cervical
      cancer.

PMID- 30241513
TI  - New PAX2 heterozygous mutation in a child with chronic kidney disease: a case
      report and review of the literature.
AB  - BACKGROUND: We herein report a 3-year-old boy presented with chronic kidney
      disease (CKD) due to PAX2 missense mutation (C to G transversion at position 418
      in exon 4). CASE PRESENTATION: He attended our clinic with a 3-month history of
      foamy urine. Upon examination, he had reduced estimated glomerular filtration
      rate (GFR) and renal atrophy. Genetic investigations revealed that he has
      inherited a mutated PAX2 gene from his father, who had renal failure at the age
      of 20. We searched the literature and confirmed that this mutation site has not
      been reported by any other group before. CONCLUSIONS: Although renal coloboma
      syndrome (RCS) with simultaneous kidney and eye involvement is the most common
      phenotype of PAX2 mutations, current literature supports that such mutations may
      have profuse clinical manifestations and renal hypoplasia is one distinct entity
      in the spectrum.

PMID- 30241514
TI  - Muscle-specific regulation of right ventricular transcriptional responses to
      chronic hypoxia-induced hypertrophy by the muscle ring finger-1 (MuRF1) ubiquitin
      ligase in mice.
AB  - BACKGROUND: We recently identified a role for the muscle-specific ubiquitin
      ligase MuRF1 in right-sided heart failure secondary to pulmonary hypertension
      induced by chronic hypoxia (CH). MuRF1-/- mice exposed to CH are resistant to
      right ventricular (RV) dysfunction whereas MuRF1 Tg + mice exhibit impaired
      function indicative of heart failure. The present study was undertaken to
      understand the underlying transcriptional alterations in the RV of MuRF1-/- and
      MuRF1 Tg + mice. METHODS: Microarray analysis was performed on RNA isolated from
      the RV of MuRF1-/-, MuRF1 Tg+, and wild-type control mice exposed to CH. RESULTS:
      MuRF1-/- RV differentially expressed 590 genes in response to CH. Analysis of the
      top 66 genes (> 2-fold or < - 2-fold) revealed significant associations with
      oxidoreductase, transcription regulation, and transmembrane component
      annotations. The significant genes had promoters enriched for HOXD12, HOXC13, and
      RREB-1 protein transcription factor binding sites. MuRF1 Tg + RV differentially
      expressed 150 genes in response to CH. Analysis of the top 45 genes (> 3-fold or
      < - 3-fold) revealed significant associations with oxidoreductase-metabolic,
      glycoprotein-transmembrane-integral proteins, and alternative splicing/splice
      variant annotations. The significant genes were enriched for promoters with ZIC1
      protein transcription factor binding sites. CONCLUSIONS: The differentially
      expressed genes in MuRF1-/- and MuRF1 Tg + RV after CH have common functional
      annotations related to oxidoreductase (including antioxidant) and transmembrane
      component functions. Moreover, the functionally-enhanced MuRF1-/- hearts regulate
      genes related to transcription, homeobox proteins, and kinases/phosphorylation.
      These studies also reveal potential indirect effects of MuRF1 through regulating
      Rreb-1, and they reveal mechanisms by which MuRF1 may transcriptionally regulate
      anti-oxidant systems in the face of right heart failure.

PMID- 30241515
TI  - PEG-L-CHOP treatment is safe and effective in adult extranodal NK/T-cell lymphoma
      with a low rate of clinical hypersensitivity.
AB  - BACKGROUND: The combination of chemotherapy and L-asparaginase (L-ASP) treatment
      significantly increased survival rate in an adult patient with extranodal natural
      killer (NK)/T-cell lymphoma (NKTCL). However, hypersensitivity reactions of L-ASP
      in some patients limited its application. Polyethylene glycol-conjugated
      asparaginase (PEG-ASP) has a lower immunogenicity and longer circulating half
      life than unconjugated L-ASP, and has been reported to be effective and well
      tolerated in children with acute lymphoblastic leukemia. Cyclophosphamide,
      hydroxydaunorubicin (doxorubicin), oncovin (vincristine), and prednisolone (CHOP)
      is the most common chemotherapy for non-Hodgkin lymphoma. In this report, we
      sought to study the efficacy and safety of PEG-L- CHOP in NKTCL in adult Chinese
      patients. METHODS: Our study is a prospective, multi-center, open-label clinical
      trial. Patients with newly diagnosed adult NKTCL and an ECOG performance status
      of 0 to 2 were eligible for enrollment. Treatment included six cycles of PEG-L
      CHOP regimen. Radiotherapy was scheduled after 2-4 cycles of PEG-L-CHOP regimen,
      depending on the stage and primary anatomic site. RESULTS: We enrolled a total of
      33 eligible patients. All 33 patients completed 170 cycles of chemotherapy
      combined with radical radiotherapy. The overall response rate was 96.9% (32/33)
      with 75.8% (25/33) achieving complete responses and 21.2% (7/33) achieving
      partial responses. The overall survival (OS) at 1, 2, 3-year were 100, 90.61 and
      80.54%, respectively. The major adverse effects were bone marrow suppression,
      reduction of fibrinogen level, liver dysfunction, and digestive tract toxicities.
      No allergic reaction and no treatment-related mortality or severe complications
      were recorded. CONCLUSIONS: PEG-L-CHOP chemotherapy in combination radiotherapy
      is safe and durably effective treatment for adult extranodal NK/T-cell lymphoma
      with fewer allergic reactions. This study was approved by the Peking University
      Beijing Cancer Hospital Ethics Review Committee (reference number: 2011101104).
      The clinical trial registration number ChiCTR1800016940 was registered on July
      07, 2018 at the Chinese Clinical Trial Registry (
      http://www.chictr.org.cn/index.aspx ). The clinical trial was registered
      retrospectively.

PMID- 30241516
TI  - Kuopio birth cohort - design of a Finnish joint research effort for
      identification of environmental and lifestyle risk factors for the wellbeing of
      the mother and the newborn child.
AB  - BACKGROUND: A Finnish joint research effort Kuopio Birth Cohort (KuBiCo) seeks to
      evaluate the effects of genetics, epigenetics and different risk factors
      (medication, nutrition, lifestyle factors and environmental aspects) during
      pregnancy on the somatic and psychological health status of the mother and the
      child. METHODS: KuBiCo will ultimately include information on 10,000 mother-child
      pairs who have given their informed consent to participate in this cohort.
      Identification of foetal health risk factors that can potentially later manifest
      as disease requires a repository of relevant biological samples and a flexible
      open up-to-date data handling system to register, store and analyse biological,
      clinical and questionnaire-based data. KuBiCo includes coded questionnaire-based
      maternal background data gathered before, during and after the pregnancy and bio
      banking of maternal and foetal samples that will be stored in deep freezers. Data
      from the questionnaires and biological samples will be collected into one
      electronic database. KuBiCo consists of several work packages which are
      complementary to each other: Maternal, foetal and placental metabolism and omics;
      Paediatrics; Mental wellbeing; Prenatal period and delivery; Analgesics and
      anaesthetics during peripartum period; Environmental effects; Nutrition; and
      Research ethics. DISCUSSION: This report describes the set-up of the KuBiCo and
      descriptive analysis from 3532 parturients on response frequencies and feedback
      to KuBiCo questionnaires gathered from June 2012 to April 2016. Additionally, we
      describe basic demographic data of the participants (n = 1172). Based on the
      comparison of demographic data between official national statistics and our
      descriptive analysis, KuBiCo represents a cross-section of Finnish pregnant
      women.

PMID- 30241517
TI  - Methods for conducting a double-blind randomized controlled clinical trial of
      three days versus five days of amoxicillin dispersible tablets for chest
      indrawing childhood pneumonia among children two to 59 months of age in Lilongwe,
      Malawi: a study protocol.
AB  - BACKGROUND: Pneumonia is the leading infectious cause of death in children under
      5 years of age around the globe. In addition to preventing pneumonia, there is a
      critical need to provide greater access to appropriate and effective treatment.
      Studies in Asia have evaluated the effectiveness of 3 days of oral amoxicillin
      for the treatment of fast-breathing pneumonia; however, further evidence is
      needed to determine if 3 days of oral amoxicillin is also effective for the
      treatment of chest indrawing pneumonia. METHODS: This is a double-blind,
      randomized, non-inferiority trial with the objective to assess the effectiveness
      of shorter duration amoxicillin dispersible tablet (DT) treatment of chest
      indrawing childhood pneumonia in a malaria-endemic region of Malawi. The primary
      objective of this study is to determine whether 3 days of treatment with oral
      amoxicillin DT in HIV-uninfected Malawian children two to 59 months of age with
      chest indrawing pneumonia is as effective as 5 days of treatment. The study will
      enroll 2000 children presenting to Kamuzu Central or Bwaila District Hospitals in
      Lilongwe, Malawi. Each child will be randomized to either 3 days of amoxicillin
      DT followed by 2 days of placebo DT or 5 days of amoxicillin DT. Children in the
      study will be hospitalized for 48 h after enrollment and will have scheduled
      study visits at Days 2, 4, 6 and 14. Treatment failure by Day 6 is the primary
      outcome. We hypothesize that the rates of treatment failure will be similar in
      both arms and that 3 days of treatment will be non-inferior to 5 days of
      amoxicillin DT for chest indrawing pneumonia using a relative non-inferiority
      margin of 1.5. This trial was approved by the Western Institutional Review Board
      and Malawi College of Medicine Research and Ethics Committee. DISCUSSION: Given
      the paucity of data from Africa, African-based research is necessary to establish
      appropriate duration of treatment with amoxicillin DT for chest indrawing
      childhood pneumonia in malaria-endemic settings in the region. An expanded
      evidence base will contribute to future iterations of World Health Organization
      Integrated Management of Childhood Illness guidelines. TRIAL REGISTRATION:
      NCT02678195 : Pre-results. Date registered February 9, 2016.

PMID- 30241518
TI  - A Chinese patient with 11beta-hydroxylase deficiency due to novel compound
      heterozygous mutation in CYP11B1 gene: a case report.
AB  - BACKGROUND: Congenital adrenal hyperplasia (CAH) resulting from steroid 11beta
      hydroxylase deficiency (11beta-OHD) is caused by mutations in the CYP11B1 gene.
      It is the second major form of CAH associated with hypertension and
      hypopotassemia. The aim of this study was to provide a genetic analysis of 11beta
      OHD in a Chinese family. CASE PRESENTATION: A 19-year-old Chinese man was
      clinically diagnosed with 11beta-OHD. His initial clinical manifestations
      included precocious puberty, hyperpigmentation, hypertension, and hypopotassemia.
      The patient had taken an overdose of dexamethasone (0.75 mg/d) for more than 10
      years before finally developing iatrogenic Cushing's syndrome. Our aim was to
      perform a molecular diagnosis of his family. Mutations in the CYP11B1 gene of the
      patient and his parents were examined using polymerase chain reaction (PCR)
      resequencing. Additionally, to predict the possible effects of novel mutations on
      the structure and function of 11beta-hydroxylase, these mutations were analyzed
      by MutationTaster software. Two novel pathogenic mutations were found in the
      CYP11B1 gene: a heterozygous in-frame insertion deletion mutation
      c.1440_1447delinsTAAAAG in exon 9 inherited from the father and a heterozygous
      mutation c.1094_1120delTGCGTGCGGCCCTCAAGGAGACCTTGC (p.364_372del) in exon 6
      inherited from the mother. CONCLUSIONS: A clear genetic diagnosis can be made by
      analyzing the functional and structural consequences of CYP11B1 gene mutations
      that lead to 11beta-OHD. Because the dosage of glucocorticoid should be adjusted
      to minimize the risk of iatrogenic Cushing's syndrome, clinical follow-up should
      be conducted with these patients.

PMID- 30241519
TI  - The impact of HIV on the prevalence of asthma in Uganda: a general population
      survey.
AB  - BACKGROUND: HIV and asthma are highly prevalent diseases in Africa but few
      studies have assessed the impact of HIV on asthma prevalence in high HIV burden
      settings. The objective of this analysis was to compare the prevalence of asthma
      among persons living with HIV (PLHIV) and those without HIV participating in the
      Uganda National Asthma Survey (UNAS). METHODS: UNAS was a population-based survey
      of persons aged >=12 years. Asthma was diagnosed based on either self-reported
      current wheeze concurrently or within the prior 12 months; physician diagnosis;
      or use of asthma medication. HIV was defined based on confidential self-report.
      We used Poisson regression with robust standard errors to estimate asthma
      prevalence and the prevalence ratio (PR) for HIV and asthma. RESULTS: Of 3416
      participants, 2067 (60.5%) knew their HIV status and 103 (5.0%) were PLHIV.
      Asthma prevalence was 15.5% among PLHIV and 9.1% among those without HIV, PR
      1.72, (95%CI 1.07-2.75, p = 0.025). HIV modified the association of asthma with
      the following factors, PLHIV vs. not PLHIV: tobacco smoking (12% vs. 8%, p = <
      0.001), biomass use (11% vs. 7%, p = < 0.001), allergy (17% vs. 11%, p = <
      0.001), family history of asthma (17% vs. 11%, p = < 0.001), and prior TB
      treatment (15% vs. 10%, p = < 0.001). CONCLUSION: In Uganda the prevalence of
      asthma is higher in PLHIV than in those without HIV, and HIV interacts
      synergistically with other known asthma risk factors. Additional studies should
      explore the mechanisms underlying these associations. Clinicians should consider
      asthma as a possible diagnosis in PLHIV presenting with respiratory symptoms.

PMID- 30241520
TI  - Service provision of non-invasive prenatal testing for Down syndrome in public
      and private healthcare sectors: a qualitative study with obstetric providers.
AB  - BACKGROUND: Cell-free fetal DNA sequencing based non-invasive prenatal testing
      (NIPT) for Down syndrome (DS) has become widely available. In Hong Kong,
      obstetric providers in the public sector refer women identified at high risk of
      having a child with Down syndrome to obstetric providers in the private sector
      for NIPT. Little is known about how the NIPT has been adopted in the public
      sector where DS screening is provided for free of charge. The study aimed to
      identify the factors influencing providers' role enactment, such as consultation
      and referral, in the service provision of NIPT for DS in public and private
      healthcare sectors. METHODS: In-depth interviews were conducted with 20 obstetric
      providers offering NIPT in Hong Kong. Thematic narrative analysis was used to
      identify (i) the factors considered by participants when referring women for NIPT
      for Down syndrome in public and private healthcare sectors and (ii) their
      perceptions of the need to integrate NIPT into the current public antenatal
      service. RESULTS: Participants raised concerns about the lack of transparent
      referral guideline between public and private sectors for NIPT. Public obstetric
      providers reported little obligation to provide women with much information about
      risks and benefits of NIPT as it was not provided by public sectors. Some private
      providers assumed that women referred from the public sector had already received
      sufficient information about NIPT. The providers were also concerned about
      potential application of NIPT for further detection without regulation.
      CONCLUSIONS: Although the providers had good knowledge of clinical advantages of
      NIPT over conventional screening, they were uncertain about how to introduce NIPT
      to women. Guidelines are necessary to enable better coordination of public and
      private sectors services to enable women to make informed choices about the
      uptake of NIPT.

PMID- 30241521
TI  - Misconceptions and traditional practices towards infant teething symptoms among
      mothers in Southwest Ethiopia.
AB  - BACKGROUND: The assumption of a link between common symptoms such as febrile
      illness, diarrhea and the eruption of primary teeth has been established over
      many centuries. According to traditional beliefs in Ethiopia, diarrhea and fever
      at the time of milk teeth eruption may be due to a worm in the child's gums.
      Current medical observations show little more than restlessness, drooling, and
      finger sucking resulting from teething. The purpose of this research was to
      assess mothers' traditional beliefs and practices towards teething symptoms.
      METHODS: A cross-sectional descriptive study design was used with the convenience
      sampling technique. Mothers were approached at the pediatric Out Patient
      Department (OPD) of Jimma University Specialized Hospital, southwest Ethiopia. A
      structured questionnaire was used for data collection. The data were analyzed by
      SPSS (version 20). RESULTS: A total of 107 mothers were interviewed. Ninety-eight
      (91.6%) claimed that teething was associated with various symptoms. Ninety-seven
      (90.7%) attributed diarrhea to teething. Only one mother said she would give her
      child Paracetamol to relieve the teething symptoms. Five (4.7%) mothers said they
      would allow their children to bite on a pacifier. Ten mothers (9.3%) said that
      they would prefer the child's milk tooth to be extracted. Some of the practices
      by mothers to relieve the symptoms include rubbing the gum of the child with
      garlic (12.1%) or rubbing the gum with herbs (6.5%). CONCLUSIONS: Most of the
      mothers had misconceptions about the symptoms that usually appear during
      teething. Health education should be provided by dentists and professionals
      concerned with child care in correcting these misconceptions and cultural beliefs
      about teething symptoms.

PMID- 30241522
TI  - Tuberculosis caused by Mycobacterium bovis infection in a captive-bred American
      bullfrog (Lithobates catesbeiana).
AB  - BACKGROUND: Tuberculosis is widely known as a progressive disease that affects
      endothermic animals, leading to death and/or economical losses, while
      mycobacterial infections in amphibians are commonly due to nontuberculous
      mycobacteria. To the authors' knowledge, this report describes the first case of
      bovine tuberculosis in a poikilothermic animal. CASE PRESENTATION: An adult
      female captive American bullfrog (Lithobates catesbeianus Shaw, 1802) died in a
      Brazilian aquarium. Multiple granulomas with acid-fast bacilli were observed in
      several organs. Identification of Mycobacterium bovis was accomplished by culture
      and PCR methods. The other animals from the same enclosure were euthanized, but
      no evidence of mycobacterial infection was observed. CONCLUSIONS: The American
      bullfrog was introduced in several countries around the world as an alternative
      husbandry, and its production is purposed for zoological and aquarium
      collections, biomedical research, education, human consumption and pet market.
      The present report warns about an episode of bovine tuberculosis in an amphibian,
      therefore further studies are necessary to define this frog species' role in the
      epidemiology of M. bovis.

PMID- 30241523
TI  - Qualitative perspectives of primary care providers who treat Medicaid managed
      care patients.
AB  - BACKGROUND: Declining job satisfaction and concurrent reductions in Medicaid
      participation among primary care providers have been documented, but there is
      limited qualitative work detailing their first-hand experiences treating Medicaid
      patients. The objective of this study is to describe the experiences of some
      primary care providers who treat Medicaid patients using in-depth qualitative
      analysis. METHODS: We conducted qualitative interviews with 15 primary care
      providers treating Medicaid patients in a Northeastern state. Participant
      recruitment efforts focused on including different types of primary care
      providers practicing in diverse settings. Qualitative interviews were conducted
      using a semi-structured interview protocol. We developed a coding scheme to
      analyze interview transcripts and identify themes. RESULTS: Providers expressed
      challenges effectively meeting their patients' needs under current policy. They
      described low Medicaid reimbursement and underinvestment in care coordination
      programs to adequately address the social determinants of health. Providers
      shared other concerns including poor access to behavioral health services,
      discontinuous Medicaid coverage due to enrollment and renewal policies, and
      limited reimbursement for alternative pain treatment. Providers offered their own
      suggestions for the allocation of financial investments, Medicaid policy, and
      primary care practice. CONCLUSIONS: Underinvestment in primary care in Medicaid
      may detract from providers' professional satisfaction and hinder care
      coordination for Medicaid patients with complex healthcare needs. Policy
      solutions that improve the experience of primary care providers serving Medicaid
      patients are urgently needed to ensure sustainability of the workforce and
      improve care delivery.

PMID- 30241524
TI  - Stress, coping, and psychological resilience among physicians.
AB  - BACKGROUND: Recent research has demonstrated that burnout is widespread among
      physicians, and impacts their wellbeing, and that of patients. Such data have
      prompted efforts to teach resilience among physicians, but efforts are hampered
      by a lack of understanding of how physicians experience resilience and stress.
      This study aimed to contribute to knowledge regarding how physicians define
      resilience, the challenges posed by workplace stressors, and strategies which
      enable physicians to cope with these stressors. METHODS: A qualitative approach
      was adopted, with 68 semi-structured interviews conducted with Irish physicians.
      Data were analysed using deductive content-analysis. RESULTS: Five themes emerged
      from the interviews. The first theme, 'The Nature of Resilience' captured
      participants' understanding of resilience. Many of the participants considered
      resilience to be "coping", rather than "thriving" in instances of adversity. The
      second theme was 'Challenges of the Profession', as participants described
      workplace stressors which threatened their wellbeing, including long shifts, lack
      of resources, and heavy workloads. The third theme, 'Job-related Gratification',
      captured aspects of the workplace that support resilience, such as gratification
      from medical efficacy. 'Resilience Strategies (Protective Practices)' summarised
      coping behaviours that participants considered to be beneficial to their
      wellbeing, including spending time with family and friends, and the final theme,
      'Resilience Strategies (Attitudes)', captured attitudes which protected against
      stress and burnout. CONCLUSIONS: This study emphasised the need for further
      research the mechanisms of physician coping in the workplace and how we can
      capitalise on insights into physicians' experiences of coping with system-level
      stressors to develop interventions to improve resilience.

PMID- 30241525
TI  - Role of phosphate limitation and pyruvate decarboxylase in rewiring of the
      metabolic network for increasing flux towards isoprenoid pathway in a TATA
      binding protein mutant of Saccharomyces cerevisiae.
AB  - BACKGROUND: Production of isoprenoids, a large and diverse class of commercially
      important chemicals, can be achieved through engineering metabolism in
      microorganisms. Several attempts have been made to reroute metabolic flux towards
      isoprenoid pathway in yeast. Most approaches have focused on the core isoprenoid
      pathway as well as on meeting the increased precursors and cofactor requirements.
      To identify unexplored genetic targets that positively influence the isoprenoid
      pathway activity, a carotenoid based genetic screen was previously developed and
      three novel mutants of a global TATA binding protein SPT15 was isolated for
      heightened isoprenoid flux in Saccharomyces cerevisiae. RESULTS: In this study,
      we investigated how one of the three spt15 mutants, spt15_Ala101Thr, was leading
      to enhanced isoprenoid pathway flux in S. cerevisiae. Metabolic flux analysis of
      the spt15_Ala101Thr mutant initially revealed a rerouting of the central carbon
      metabolism for the production of the precursor acetyl-CoA through activation of
      pyruvate-acetaldehyde-acetate cycle in the cytoplasm due to high flux in the
      reaction caused by pyruvate decarboxylase (PDC). This led to alternate routes of
      cytosolic NADPH generation, increased mitochondrial ATP production and phosphate
      demand in the mutant strain. Comparison of the transcriptomics of the
      spt15_Ala101Thr mutant cell with SPT15WT bearing cells shows upregulation of
      phosphate mobilization genes and pyruvate decarboxylase 6 (PDC6). Increasing the
      extracellular phosphate led to an increase in the growth rate and biomass but
      diverted flux away from the isoprenoid pathway. PDC6 is also shown to play a
      critical role in isoprenoid pathway flux under phosphate limitation conditions.
      CONCLUSION: The study not only proposes a probable mechanism as to how a
      spt15_Ala101Thr mutant (a global TATA binding protein mutant) could increase flux
      towards the isoprenoid pathway, but also PDC as a new route of metabolic
      manipulation for increasing the isoprenoid flux in yeast.

PMID- 30241526
TI  - Proteogenomic characterization and comprehensive integrative genomic analysis of
      human colorectal cancer liver metastasis.
AB  - BACKGROUND: Proteogenomic characterization and integrative and comparative
      genomic analysis provide a functional context to annotate genomic abnormalities
      with prognostic value. METHODS: Here, we analyzed the proteomes and performed
      whole exome and transcriptome sequencing and single nucleotide polymorphism array
      profiling for 2 sets of triplet samples comprised of normal colorectal tissue,
      primary CRC tissue, and synchronous matched liver metastatic tissue. RESULTS: We
      identified 112 CNV-mRNA-protein correlated molecules, including up-regulated
      COL1A2 and BGN associated with prognosis, and four strongest hot spots
      (chromosomes X, 7, 16 and 1) driving global mRNA abundance variation in CRC liver
      metastasis. Two sites (DMRTB1R202H and PARP4V458I) were revealed to frequent
      mutate only in the liver metastatic cohort and displayed dysregulated protein
      abundance. Moreover, we confirmed that the mutated peptide number has potential
      prognosis value and somatic variants displayed increased protein abundance,
      including high MYH9 and CCT6A expression, with clinical significance.
      CONCLUSIONS: Our proteogenomic characterization and integrative and comparative
      genomic analysis provides a new paradigm for understanding human colon and rectal
      cancer liver metastasis. TRIAL REGISTRATION: ClinicalTrials, NCT02917707.
      Registered 28 September 2016, https://clinicaltrials.gov/ct2/show/NCT02917707 .

PMID- 30241527
TI  - Development and validation of a new instrument to measure perceived risks
      associated with the use of tobacco and nicotine-containing products.
AB  - BACKGROUND: Making tobacco products associated with lower risks available to
      smokers who would otherwise continue smoking is recognized as an important
      strategy towards addressing smoking-related harm. Predicting use behavior is an
      important major component of product risk assessment. In this context, risk
      perception is a possible factor driving tobacco product uptake and use. As prior
      to market launch real-world actual product use cannot be observed, assessing risk
      perception can provide predictive information. Considering the lack of suitable
      validated self-report instruments, the development of a new instrument was
      undertaken to quantify perceived risks of tobacco and nicotine-containing
      products by adult smokers, former smokers and never-smokers. METHODS: Initial
      items were constructed based on a literature review, focus groups and expert
      opinion. Data for scale formation and assessment were obtained through two
      successive US-based web surveys (n = 2020 and 1640 completers, respectively).
      Psychometric evaluation was based on Rasch Measurement Theory and Classical Test
      Theory. RESULTS: Psychometric evaluation supported the formation of an 18-item
      Perceived Health Risk scale and a 7-item Perceived Addiction Risk scale: item
      response option thresholds were ordered correctly for all items; item locations
      in each scale were spread out (coverage range 75-87%); scale reliability was
      supported by high person separation indices > 0.93, Cronbach's alpha > 0.98 and
      Corrected Item-Total Correlations > 0.88; and no differential item functioning
      was present. Construct validity evaluations met expectations through inter-scale
      correlations and findings from known-group comparisons. CONCLUSIONS: The
      Perceived Risk Instrument is a psychometrically robust instrument applicable for
      general and personal risk perception measurement, for use in different types of
      products (including cigarettes, nicotine replacement therapy, potential Modified
      Risk Tobacco Products), and for different smoking status groups (i.e., current
      smokers with and without intention to quit, former smokers, never smokers).

PMID- 30241528
TI  - Development of a strictly regulated xylose-induced expression system in
      Streptomyces.
AB  - BACKGROUND: Genetic tools including constitutive and inducible promoters have
      been developed over the last few decades for strain engineering in Streptomyces.
      Inducible promoters are useful for controlling gene expression, however only a
      limited number are applicable to Streptomyces. The aim of this study is to
      develop a controllable protein expression system based on an inducible promoter
      using sugar inducer, which has not yet been widely applied in Streptomyces.
      RESULTS: To determine a candidate promoter, inducible protein expression was
      first examined in Streptomyces avermitilis MA-4680 using various carbon sources.
      Xylose isomerase (xylA) promoter derived from xylose (xyl) operon was selected
      due to strong expression of xylose isomerase (XylA) in the presence of D-xylose.
      Next, a xylose-inducible protein expression system was constructed by
      investigating heterologous protein expression (chitobiase as a model protein)
      driven by the xylA promoter in Streptomyces lividans. Chitobiase activity was
      detected at high levels in S. lividans strain harboring an expression vector with
      xylA promoter (pXC), under both xylose-induced and non-induced conditions. Thus,
      S. avermitilis xylR gene, which encodes a putative repressor of xyl operon, was
      introduced into constructed vectors in order to control protein expression by D
      xylose. Among strains constructed in the study, XCPR strain harboring pXCPR
      vector exhibited strict regulation of protein expression. Chitobiase activity in
      the XCPR strain was observed to be 24 times higher under xylose-induced
      conditions than that under non-induced conditions. CONCLUSION: In this study, a
      strictly regulated protein expression system was developed based on a xylose
      induced system. As far as we could ascertain, this is the first report of
      engineered inducible protein expression in Streptomyces by means of a xylose
      induced system. This system might be applicable for controllable expression of
      toxic products or in the field of synthetic biology using Streptomyces strains.

PMID- 30241529
TI  - Safety and immunogenicity of an attenuated Chinese pseudorabies variant by dual
      deletion of TK&gE genes.
AB  - BACKGROUND: Since the outbreak of a new emerging virulent pseudorabies virus
      mutant in Chinese pig herds, intensive research has been focused on the
      construction of novel gene deletion vaccine based on the variant virulent
      viruses. An ideal vaccine candidate is expected to have a balanced safety and
      immunogenicity. RESULTS: From the infectious clone of PRV AH02LA strain, a TK
      deletion mutant was generated through two-step Red mutagenesis. After homologous
      recombination with a transfer vector, a TK&gE dual deficient mutant PRV
      (PRVDeltaTK&gE-AH02) was generated, and its structure verified by PCR, RFLP and
      sequencing. Growth kinetics test showed that PRVDeltaTK&gE-AH02 reached a titer
      of 107.5 TCID50 /mL on ST cells. The PRVDeltaTK&gE-AH02 at a dose of 106.0 TCID50
      /animal was not virulent in mice or 1-day-old piglets with maternal PRV
      antibodies. No clinical signs or virus shedding were detected in 28~ 35-day-old
      piglets without maternal PRV antibodies after nasal or intramuscular
      administration with a dose of 106.0 TCID50, although it caused one death of four
      1-day-old piglets without maternal PRV antibodies. In the efficiency test of
      PRVDeltaTK&gE-AH02, all four 28~ 35-day-old piglets without PRV antibody in the
      challenge control showed typical clinical symptoms and virus shedding, and two
      died at 4~ 5 days post challenge. All piglets in 105.0, 104.0 and 103.0
      TCID50/dose PRVDeltaTK&gE-AH02 groups provided complete protection against
      challenge at only 7 days post intramuscular vaccination. More importantly,
      PRVDeltaTK&gE-AH02 stopped virus shedding in these piglets. In contrast, all four
      piglets in PRV Bartha K61 vaccine group developed high body temperature (>=40.5 
      degrees C) and viral shedding, despite they had mild or even no clinical
      symptoms. CONCLUSIONS: The constructed TK&gE dual deletion mutant PRVDeltaTK&gE
      AH02 can reach high titers on ST cells. The live vaccine of PRVDeltaTK&gE-AH02 is
      highly safe, and can not only provide clinical protection but also stops virus
      shedding. This study suggests that PRVDeltaTK&gE-AH02 might work as a promising
      vaccine candidate to combat the PRV variant emerging in Chinese herds since 2011.

PMID- 30241530
TI  - Evaluation of GFP reporter utility for analysis of transcriptional slippage
      during gene expression.
AB  - BACKGROUND: Epimutations arising from transcriptional slippage seem to have more
      important role in regulating gene expression than earlier though. Since the level
      and the fidelity of transcription primarily determine the overall efficiency of
      gene expression, all factors contributing to their decrease should be identified
      and optimized. RESULTS: To examine the influence of A/T homopolymeric sequences
      on introduction of erroneous nucleotides by slippage mechanism green fluorescence
      protein (GFP) reporter was chosen. The in- or out-of-frame gfp gene was fused to
      upstream fragment with variable number of adenine or thymine stretches resulting
      in several hybrid GFP proteins with diverse amino acids at N-terminus. Here, by
      using T7 phage expression system we showed that the intensity of GFP fluorescence
      mainly depends on the number of the retained natural amino acids. While the lack
      of serine (S2) residue results in negligible effects, the lack of serine and
      lysine (S2K3) contributed to a significant reduction in fluorescence by 2.7-fold
      for polyA-based in-frame controls and twofold for polyTs. What is more, N
      terminal tails amino acid composition was rather of secondary importance, since
      the whole-cell fluorescence differed in a range of 9-18% between corresponding
      polyA- and polyT-based constructs. CONCLUSIONS: Here we present experimental
      evidence for utility of GFP reporter for accurate estimation of A/T homopolymeric
      sequence contribution in transcriptional slippage induction. We showed that the
      intensity of GFP hybrid fluorescence mainly depends on the number of retained
      natural amino acids, thus fluorescence raw data need to be referred to
      appropriate positive control. Moreover, only in case of GFP hybrids with
      relatively short N-terminal tags the fluorescence level solely reflects
      production yield, what further indicates the impact of an individual slippage
      sequence. Our results demonstrate that in contrast to the E. coli enzyme, T7 RNA
      polymerase exhibits extremely high propensity to slippage even on runs as short
      as 3 adenine or 4 thymine residues.

PMID- 30241532
TI  - Acceptability of prison-based take-home naloxone programmes among a cohort of
      incarcerated men with a history of regular injecting drug use.
AB  - BACKGROUND: Take-home naloxone (THN) programmes are an evidence-based opioid
      overdose prevention initiative. Elevated opioid overdose risk following prison
      release means release from custody provides an ideal opportunity for THN
      initiatives. However, whether Australian prisoners would utilise such programmes
      is unknown. We examined the acceptability of THN in a cohort of male prisoners
      with histories of regular injecting drug use (IDU) in Victoria, Australia.
      METHODS: The sample comprised 380 men from the Prison and Transition Health
      (PATH) Cohort Study; all of whom reported regular IDU in the 6 months prior to
      incarceration. We asked four questions regarding THN during the pre-release
      baseline interview, including whether participants would be willing to
      participate in prison-based THN. We describe responses to these questions along
      with relationships between before- and during-incarceration factors and
      willingness to participate in THN training prior to release from prison. RESULTS:
      Most participants (81%) reported willingness to undertake THN training prior to
      release. Most were willing to resuscitate a friend using THN if they were trained
      (94%) and to be revived by a trained peer (91%) using THN. More than 10 years
      since first injection (adjusted odds ratio [AOR] 2.22, 95%CI 1.03-4.77), having
      witnessed an opioid overdose in the last 5 years (AOR 2.53, 95%CI 1.32-4.82),
      having ever received alcohol or other drug treatment in prison (AOR 2.41, 95%CI
      1.14-5.07) and injecting drugs during the current prison sentence (AOR 4.45,
      95%CI 1.73-11.43) were significantly associated with increased odds of
      willingness to participate in a prison THN programme. Not specifying whether they
      had injected during their prison sentence (AOR 0.37, 95%CI 0.18-0.77) was
      associated with decreased odds of willingness to participate in a prison THN
      training. CONCLUSION: Our findings suggest that male prisoners in Victoria with a
      history of regular IDU are overwhelmingly willing to participate in THN training
      prior to release. Factors associated with willingness to participate in prison
      THN programmes offer insights to help support the implementation and uptake of
      THN programmes to reduce opioid-overdose deaths in the post-release period.

PMID- 30241531
TI  - Production of p-amino-L-phenylalanine (L-PAPA) from glycerol by metabolic
      grafting of Escherichia coli.
AB  - BACKGROUND: The non-proteinogenic aromatic amino acid, p-amino-L-phenylalanine (L
      PAPA) is a high-value product with a broad field of applications. In nature, L
      PAPA occurs as an intermediate of the chloramphenicol biosynthesis pathway in
      Streptomyces venezuelae. Here we demonstrate that the model organism Escherichia
      coli can be transformed with metabolic grafting approaches to result in an
      improved L-PAPA producing strain. RESULTS: Escherichia coli K-12 cells were
      genetically engineered for the production of L-PAPA from glycerol as main carbon
      source. To do so, genes for a 4-amino-4-deoxychorismate synthase (pabAB from
      Corynebacterium glutamicum), and genes encoding a 4-amino-4-deoxychorismate
      mutase and a 4-amino-4-deoxyprephenate dehydrogenase (papB and papC, both from
      Streptomyces venezuelae) were cloned and expressed in E. coli W3110 (lab strain
      LJ110). In shake flask cultures with minimal medium this led to the formation of
      ca. 43 +/- 2 mg l-1 of L-PAPA from 5 g l-1 glycerol. By expression of additional
      chromosomal copies of the tktA and glpX genes, and of plasmid-borne aroFBL genes
      in a tyrR deletion strain, an improved L-PAPA producer was obtained which gave a
      titer of 5.47 +/- 0.4 g l-1 L-PAPA from 33.3 g l-1 glycerol (0.16 g L-PAPA/g of
      glycerol) in fed-batch cultivation (shake flasks). Finally, in a fed-batch
      fermenter cultivation, a titer of 16.7 g l-1 L-PAPA was obtained which is the
      highest so far reported value for this non-proteinogenic amino acid. CONCLUSION:
      Here we show that E. coli is a suitable chassis strain for L-PAPA production.
      Modifying the flux to the product and improved supply of precursor, by additional
      gene copies of glpX, tkt and aroFBL together with the deletion of the tyrR gene,
      increased the yield and titer.

PMID- 30241534
TI  - Critical assessment of refugees' needs in post-emergency context: the case of
      Malian war refugees settled in Northern Burkina Faso.
AB  - BACKGROUND: Empirically assessing the needs of refugees in camps is critical to
      the improvement of existing policies and programs that aim at enhancing their
      well-being. By neglecting the needs of refugees, interventions may fail to
      capture the complex patterns of refugees' daily lives within camps. This paper
      provides a comprehensive assessment of the needs of encamped Malian refugees in
      Northern Burkina Faso following the 2012-armed conflict. In addition to assessing
      the needs of Malian refugees, the study aimed to critically assess from an
      upstream perspective the degree of their involvement in policies and practices
      that are targeted towards improving their livelihood. METHODS: We took an
      "upstream" view on the lives of Malian refugees to identify their unmet needs. A
      purposive sampling strategy was employed to collect data from various media
      sources, including data aggregated from the website of the United Nations High
      Commissioner for Refugees (UNHCR). The most populous refugee camp (Mentao) was
      visited in September 2012 and in-depth group discussion and interviews were
      conducted with key informants, including nine camp representatives and four
      officials from the central and decentralized administrations. RESULTS: Media
      canvass combined with the UNHCR level 2 census revealed a flawed headcount of
      refugees, which was 205.4% higher than the real number in Burkina Faso. Although
      refugees live harmoniously with the natives and their security has been assured,
      they strongly complained about the number of unused food items distributed. Camps
      were distributed among humanitarian organizations leading to differential
      advantage and resources from one camp to another. Additionally, idleness, lack of
      classrooms facilities for pre-school children and lack of continuous healthcare
      services were major concerns raised. Further, refugees expressed limited
      involvement in the planning and implementation of programs that are related to
      their welfare. CONCLUSION: This study revealed that refugees' voices were not
      taken into consideration in making tailor-made programs. This calls for more
      comprehensive surge capacity to deal with refugees' basic needs. Further, a
      strong leadership from hoststate should be encouraged to offer equal
      opportunities to refugees regardless of their camps. Finally, an innovative
      strategy is needed to build a reliable database that could enhance the design,
      implementation, monitoring and evaluation of policies and programs.

PMID- 30241533
TI  - Combined plasma rich in growth factors and adipose-derived mesenchymal stem cells
      promotes the cutaneous wound healing in rabbits.
AB  - BACKGROUND: The use of Plasma Rich in Growth Factors (PRGF) and Adipose Derived
      Mesenchymal Stem Cells (ASCs) are today extensively studied in the field of
      regenerative medicine. In recent years, human and veterinary medicine prefer to
      avoid using traumatic techniques and choose low or non-invasive procedures. The
      objective of this study was to evaluate the efficacy of PRGF, ASCs and the
      combination of both in wound healing of full-thickness skin defects in rabbits.
      With this purpose, a total of 144 rabbits were used for this study. The animals
      were divided in three study groups of 48 rabbits each depending on the
      administered treatment: PRGF, ASCs, and PGRF+ASCs. Two wounds of 8 mm of diameter
      and separated from each other by 20 mm were created on the back of each rabbit:
      the first was treated with saline solution, and the second with the treatment
      assigned for each group. Macroscopic and microscopic evolution of wounds was
      assessed at 1, 2, 3, 5, 7 and 10 days post-surgery. With this aim, 8 animals from
      each treatment group and at each study time were euthanized to collect wounds for
      histopathological study. RESULTS: Wounds treated with PRGF, ASCs and PRGF+ASCs
      showed significant higher wound healing and epithelialization rates, more natural
      aesthetic appearance, significant lower inflammatory response, significant higher
      collagen deposition and angiogenesis compared with control wounds. The combined
      treatment PRGF+ASCs showed a significant faster cutaneous wound healing process.
      CONCLUSIONS: The combined treatment PRGF+ASCs showed the best results, suggesting
      this is the best choice to enhance wound healing and improve aesthetic results in
      acute wounds.

PMID- 30241535
TI  - Dynamic stability and spatiotemporal parameters during turning in healthy young
      adults.
AB  - BACKGROUND AND PURPOSE: Turning while walking has a frequent occurrence in daily
      life. Evaluation of its dynamic stability will facilitate fall prevention and
      rehabilitation scheme. This knowledge is so limited that we set it as the first
      aim of this study. Another aim was to investigate spatiotemporal parameters
      during turning. METHODS: Fifteen healthy young adults were instructed to perform
      straight walking, 45 degrees  step turn to the left and 45 degrees  spin turn to
      the right at natural speed. Dynamic stability was measured by margin of stability
      (MoS) in anterior, posterior, left and right direction at each data point where
      significant differences were detected using 95% bootstrap confidence band. Common
      spatiotemporal parameters were computed in each condition subdivided into
      approach, turn and depart phases. RESULTS: Results showed that minimum anterior
      MoS appeared at middle of swing while minimum lateral MoS at contralateral heel
      strike in all conditions. Posterior MoS decreased before middle of turn phase in
      spin whereas after middle of turn phase in step. Lateral MoS and stride width
      declined in turn phase of spin while in depart of step. Spin had a long step and
      stride length. Long swing phases were observed in turns. CONCLUSIONS: These data
      help explain that people are most likely to fall forward at middle of swing and
      to fall toward the back and the support side at heel strike. Our findings
      demonstrate that instability mainly exist in turn phase of spin and depart phase
      of step turn.

PMID- 30241537
TI  - An ensemble of mathematical models showing diauxic growth behaviour.
AB  - BACKGROUND: Carbon catabolite repression (CCR) controls the order in which
      different carbon sources are metabolised. Although this system is one of the
      paradigms of regulation in bacteria, the underlying mechanisms remain
      controversial. CCR involves the coordination of different subsystems of the cell 
      responsible for the uptake of carbon sources, their breakdown for the production
      of energy and precursors, and the conversion of the latter to biomass. The
      complexity of this integrated system, with regulatory mechanisms cutting across
      metabolism, gene expression, and signalling, has motivated important modelling
      efforts over the past four decades, especially in the enterobacterium Escherichia
      coli. RESULTS: Starting from a simple core model with only four intracellular
      metabolites, we develop an ensemble of model variants, all showing diauxic growth
      behaviour during a batch process. The model variants fall into one of the four
      categories: flux balance models, kinetic models with growth dilution, kinetic
      models with regulation, and resource allocation models. The model variants differ
      from one another in only a single aspect, each breaking the symmetry between the
      two substrate assimilation pathways in a different manner, and can be
      quantitatively compared using a so-called diauxic growth index. For each of the
      model variants, we predict the behaviour in two new experimental conditions,
      namely a glucose pulse for a culture growing in minimal medium with lactose and a
      batch culture with different initial concentrations of the components of the
      transport systems. When qualitatively comparing these predictions with
      experimental data for these two conditions, a number of models can be excluded
      while other model variants are still not discriminable. The best-performing model
      variants are based on inducer inclusion and activation of enzymatic genes by a
      global transcription factor, but the other proposed factors may complement these
      well-known regulatory mechanisms. CONCLUSIONS: The model ensemble presented here
      offers a better understanding of the variety of mechanisms that have been
      proposed to play a role in CCR. In addition, it provides an educational resource
      for systems biology, as it gives an introduction to a broad range of modeling
      approaches in the context of a simple but biologically relevant example.

PMID- 30241536
TI  - Association between whole grain intake and breast cancer risk: a systematic
      review and meta-analysis of observational studies.
AB  - BACKGROUND: Epidemiological studies have found that high whole grain intake may
      be associated with a reduced risk of breast cancer. However, the evidence has not
      been consistent. We conducted a meta-analysis to quantitatively assess the
      association between whole grain intake and breast cancer risk. METHODS: Relevant
      observational studies were identified by searching PubMed, Embase, Cochrane
      library databases, and Google Scholar through April 2017. Summary relative risk
      (RR) estimates were calculated using random-effects meta-analysis. RESULTS: A
      total of 11 studies, including 4 cohort and 7 case-control studies and involving
      131,151 participants and 11,589 breast cancer cases, were included in the current
      meta-analysis. The pooled RR of breast cancer for those with high versus low
      whole grain intake was 0.84 (95% confidence interval [CI]: 0.74 to 0.96, p =
      0.009; I2 = 63.8%, p for heterogeneity = 0.002). Subgroup analysis by study
      design found a significant inverse association in the case-control studies (RR:
      0.69; 95% CI: 0.56 to 0.87, p = 0.001; I2 = 58.2%, p for heterogeneity = 0.026),
      but not in the cohort studies (RR, 0.96; 95% CI: 0.82 to 1.14, p = 0.69; I2 =
      66.7%, p for heterogeneity = 0.029). In addition, stratified analysis suggested
      that sample size could be a potential source of heterogeneity. CONCLUSIONS:
      Results of the current meta-analysis suggest that high intake of whole grains
      might be inversely associated with a reduced risk of breast cancer, and the
      inverse association was only observed in case-control but not cohort studies.
      More large-scale cohort studies are needed to confirm the inverse association
      observed.

PMID- 30241538
TI  - Assessing utility values for treatment-related health states of acute myeloid
      leukemia in the United States.
AB  - BACKGROUND: Preference valuations of health status are essential in health
      technology and economic appraisal. This study estimated utilities for treatment
      related health states of acute myeloid leukemia (AML) and disutilities of severe
      adverse events (SAEs) using a representative sample of adults from the general
      population in the United States (US). METHODS: Treatment-related AML health
      states, defined based on literature and interviews with clinicians, included
      complete remission (CR), no CR, relapse, stem cell transplant (SCT), and post SCT
      short-term recovery. Six attributes with varying levels, including fever, lack of
      energy, problems with daily function, anxiety/depression, blood transfusions, and
      hospitalization, were used to define health states. An online survey using
      discrete choice experiment methodology was designed to capture preferences for
      health status scenarios including the identified attributes and key grade 3/4
      chemotherapy-related SAEs. Health state utilities and SAE disutilities were
      generated from a conditional logistic regression with generalized estimating
      equations. RESULTS: Of the 300 survey participants, the demographic distributions
      were within a 3% margin of those in the 2010 US Census. CR had the highest
      utility value (0.875), followed by post-SCT short-term recovery (0.398), relapse
      (0.355), no CR (0.262), and SCT (0.158). Of the SAEs, serious infection had the
      highest decline in utility (0.218), followed by severe diarrhea (0.176),
      abnormally low blood cell counts (0.100), and severe redness/skin peeling
      (0.060). CONCLUSIONS: AML and treatments can result in reduced quality of life
      and impaired ability to perform daily activities. Findings of this study
      underline the value that society places on treatment-related AML health states
      and SAEs.

PMID- 30241539
TI  - ZIKV infection activates the IRE1-XBP1 and ATF6 pathways of unfolded protein
      response in neural cells.
AB  - BACKGROUND: Many viruses depend on the extensive membranous network of the
      endoplasmic reticulum (ER) for their translation, replication, and packaging.
      Certain membrane modifications of the ER can be a trigger for ER stress, as well
      as the accumulation of viral protein in the ER by viral infection. Then, unfolded
      protein response (UPR) is activated to alleviate the stress. Zika virus (ZIKV) is
      a mosquito-borne flavivirus and its infection causes microcephaly in newborns and
      serious neurological complications in adults. Here, we investigated ER stress and
      the regulating model of UPR in ZIKV-infected neural cells in vitro and in vivo.
      METHODS: Mice deficient in type I and II IFN receptors were infected with ZIKV
      via intraperitoneal injection and the nervous tissues of the mice were assayed at
      5 days post-infection. The expression of phospho-IRE1, XBP1, and ATF6 which were
      the key markers of ER stress were analyzed by immunohistochemistry assay in vivo.
      Additionally, the nuclear localization of XBP1s and ATF6n were analyzed by
      immunohistofluorescence. Furthermore, two representative neural cells,
      neuroblastoma cell line (SK-N-SH) and astrocytoma cell line (CCF-STTG1), were
      selected to verify the ER stress in vitro. The expression of BIP, phospho
      elF2alpha, phospho-IRE1, and ATF6 were analyzed through western blot and the
      nuclear localization of XBP1s was performed by confocal immunofluorescence
      microscopy. RT-qPCR was also used to quantify the mRNA level of the UPR
      downstream genes in vitro and in vivo. RESULTS: ZIKV infection significantly
      upregulated the expression of ER stress markers in vitro and in vivo. Phospho
      IRE1 and XBP1 expression significantly increased in the cerebellum and
      mesocephalon, while ATF6 expression significantly increased in the mesocephalon.
      ATF6n and XBP1s were translocated into the cell nucleus. The levels of BIP, ATF6,
      phospho-elf2alpha, and spliced xbp1 also significantly increased in vitro.
      Furthermore, the downstream genes of UPR were detected to investigate the
      regulating model of the UPR during ZIKV infection in vitro and in vivo. The
      transcriptional levels of atf4, gadd34, chop, and edem-1 in vivo and that of
      gadd34 and chop in vitro significantly increased. CONCLUSION: Findings in this
      study demonstrated that ZIKV infection activates ER stress in neural cells. The
      results offer clues to further study the mechanism of neuropathogenesis caused by
      ZIKV infection.

PMID- 30241540
TI  - Development of a sensitive and specific xMAP assay for detection of antibodies
      against infectious laryngotracheitis and bronchitis viruses.
AB  - BACKGROUND: A serological method to simultaneously detect antibodies against
      infectious laryngotracheitis virus (ILTV) and infectious bronchitis virus (IBV)
      is imperative for the differential diagnosis and evaluation of antibodies titers
      after vaccination. METHOD: The microspheres coated with purified recombinant
      glycoprotein D (gD) of ILTV or nucleocapsid (N) protein of IBV were incubated
      with serum samples. The simultaneous quantification of ILTV and IBV antibodies
      were achieved through the interrogation of microspheres by Luminex 200 detection
      system. . RESULTS: This xMAP detection demonstrated no nonspecific reactions with
      avian influenza virus (AIV), avian leukosis virus (ALV), newcastle disease virus
      (NDV), and Marek's disease virus (MDV). The results also demonstrated that the
      xMAP assay was four times more sensitive than the enzyme-linked immunosorbent
      assay (ELISA) for ILTV detection and two times more sensitive for IBV detection.
      A total of 90 chicken serum samples from a chicken farm were tested by xMAP and
      ELISA assays. The results showed that the coincidence rates were 84.44 and 100%
      for ILTV and IBV detection, respectively. CONCLUSION: This study exhibited an
      opportunity for the differential diagnosis through simultaneous detection of
      multiplex antibodies in serum and can be used for the multiplex antibodies
      evaluation after vaccination.

PMID- 30241541
TI  - Cellular RelB interacts with the transactivator Tat and enhance HIV-1 expression.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) Tat protein plays an
      essential role in HIV-1 gene transcription. Tat transactivates HIV-1 long
      terminal repeat (LTR)-directed gene expression through direct interactions with
      the transactivation-responsive region (TAR) element and other cis elements in the
      LTR. The TAR-independent Tat-mediated LTR transactivation is modulated by several
      host factors, but the mechanism is not fully understood. RESULTS: Here, we report
      that Tat interacts with the Rel homology domain of RelB through its core region.
      Furthermore, RelB significantly increases Tat-mediated transcription of the HIV-1
      LTR and viral gene expression, which is independent of the TAR. Both Tat and RelB
      are recruited to the HIV-1 promoter, of which RelB facilitates the recruitment of
      Tat to the viral LTR. The NF-kappaB elements are key to the accumulation of Tat
      and RelB on the LTR. Knockout of RelB reduces the accumulation of RNA polymerase
      II on the LTR, and decreases HIV-1 gene transcription. Together, our data suggest
      that RelB contributes to HIV-1 transactivation. CONCLUSIONS: Our results
      demonstrate that RelB interacts with Tat and enhances TAR-independent activation
      of HIV-1 LTR promoter, which adds new insights into the multi-layered mechanisms
      of Tat in regulating the gene expression of HIV-1.

PMID- 30241542
TI  - Understanding barriers preventing pregnant women from starting antenatal clinic
      in the first trimester of pregnancy in Ntcheu District-Malawi.
AB  - BACKGROUND: Exploring barriers contributing to low utilization of Antenatal Care
      (ANC) during the first trimester of pregnancy is of national programmatic
      importance. We conducted an exploratory study in 2013 at Bilira Health Centre in
      Ntcheu district-Malawi with an aim of understanding barriers that prevent
      pregnant women from attending antenatal clinics in the first trimester of
      pregnancy. METHOD: This was cross sectional exploratory study using qualitative
      approach. Data were collected from ANC clients, key informants, health services
      professionals and women of child bearing age (15-49 years) using an in-depth
      interviews and Focus Group Discussions (FGDs). Data were analysed manually by
      reading the transcriptions and memos several times inorder to be familiar with
      the themes emerged. The emerged themes were coded. RESULTS: Most of the women
      reported that they have a feeling of starting ANC in the early days of their
      pregnancies, however, they also reported several barriers ranging from cultural
      beliefs, social economic to service delivery barriers. On cultural barriers many
      women wait for marriage counselors from husband's side to give them advice before
      starting ANC in the process called "Kuthimba". Some women hide the pregnancy in
      early months to avoid being bewitched. On social-economic barriers, some of the
      women mentioned that they don't start ANC early waiting for new clothes. Poor
      attitude of health workers also has an effect on ANC attendants. Most women
      pointed out that they started ANC late because some health workers were rude and
      do not observe confidentiality. Men's refusal to accompany their spouses to
      antenatal clinic in fear of HIV test and some by-laws which restrict women who
      had pregnancy outside marriage to seek an authorisation letter first from
      Traditional Leaders for them to start ANC at the health facility were also
      mentioned as contributing barriers. CONCLUSION: Women should be oriented on the
      national guidelines on Focused ANC (FANC) which advocates for at least 4 visits.
      There should also be Information, Education and Communication (IEC) on ANC and
      interventions to deal with social-cultural issues while at the same time
      improving service delivery at the health facility so that ANC services can be
      accessible and responsive enough.

PMID- 30241543
TI  - Comparative effectiveness and safety of tranexamic acid plus diluted epinephrine
      to control blood loss during total hip arthroplasty: a meta-analysis.
AB  - BACKGROUND: The standard protocol to achieve haemostasis during total hip
      arthroplasty (THA) is uncertain. Tranexamic acid plus diluted epinephrine (DEP)
      and tranexamic acid (TXA) alone are the two most common alternatives. The purpose
      of this study was to compare the efficacy and safety of TXA plus DEP to treat
      blood loss in THA patients. METHODS: Published randomized controlled trials
      (RCTs) were identified from the following electronic databases: PubMed, Embase,
      Web of Science, Cochrane Library and Google from inception to July 10, 2018.
      Studies comparing TXA plus DEP with TXA alone to treat blood loss were included.
      Either a random-effects model or a fixed-effects model was used for meta-analysis
      depending on the heterogeneity. We used the need for transfusion as the primary
      outcome. Stata 12.0 was used for meta-analysis. RESULTS: Six studies involving
      703 patients were included in the present meta-analysis. The pooled results
      demonstrated that TXA plus DEP was associated with a lower transfusion rate than
      TXA alone (RR = 0.57, 95% CI 0.38-0.86, P = 0.006). Furthermore, TXA plus DEP was
      associated with less total blood loss and hidden blood loss by approximately
      209.79 ml and 297.74 ml, respectively, than TXA alone. There was no significant
      difference in terms of intraoperative blood loss or the occurrence of deep venous
      thrombosis or haematoma between the TXA plus DEP and TXA alone groups (P > 0.05).
      CONCLUSIONS: Our meta-analysis suggested that TXA plus DEP significantly
      decreased the need for transfusion, total blood loss and hidden blood loss among
      THA patients. Furthermore, TXA plus DEP did not increase the occurrence of DVT or
      haemostasis. Additional long-term follow-up RCTs are needed to identify the
      optimal doses of TXA and DEP.

PMID- 30241544
TI  - A socio-economic analysis of increased staffing in the Norwegian helicopter
      emergency medical service.
AB  - BACKGROUND: The European Aviation Safety Agency (EASA) is preparing a new set of
      regulations that will cover working and resting periods for crew members engaged
      in emergency medical services with helicopters (HEMS) and aeroplanes (AEMS). Such
      a shared European regulatory framework has already been introduced for the
      majority of commercial operations with aeroplanes, whereas national regulations
      are still in place for helicopter operations. A possible consequence of changing
      the regulations on working and resting periods for helicopter operations is that
      current abilities to provide 24-h, continuous emergency readiness with the same
      helicopter crew will be changed to a daily shift pattern with two, and even up to
      three, different crews to cover one 24-h period. METHODS: A cost-benefit study is
      used to analyse whether changed working and resting periods, through the
      introduction of a shared European framework are socio-economically profitable for
      Norwegian helicopter emergency medical service (HEMS). For the study, relevant
      data is available for the total of nine HEMS helicopters of the three regions in
      Norway, for the period 2006-2013. The aim of the study is to document whether
      changed working and resting periods will be socio-economically beneficial for the
      Norwegian HEMS. RESULTS: The expected present value of changing the current
      regulations on working and resting periods is estimated at negative 181 million
      NOK over a 40-year period. This includes the assumption that all missions that
      are not completed today due to limitation in crew availability will be completed
      upon introducing new working and resting periods. In the current regulatory
      regime for the Norwegian HEMS, there are on average seven missions per HEMS base
      annually that are not completed due to the limitations in crew availability with
      the current working and resting periods. Changing the regulations on working and
      resting periods is estimated to be cost-effective when a minimum of 14 missions
      per year are prevented from being cancelled due to crew availability. DISCUSSION:
      The benefit and cost elements used in the socio-economic analysis contain an
      estimated benefit of the measure, based on the valuation of life years gained for
      a limited number of patients. The prerequisites for life years gained, with the
      associated monetary value for quality-adjusted life years, are important for the
      outcome of the cost-benefit analysis. In this study 6.95 life years gained is
      used as basis for the benefit of the measure. This number is based on the
      conclusion of two studies, which have studied the benefits of HEMS helicopters
      staffed with a doctor in Norway. In a cost-benefit analyses, a quantification
      shall as far as possible be made in monetary values of all the positive and
      negative effects the measure entails. In this analysis, one criticism may be that
      these effects are relatively few, the investment costs (the increased operating
      costs) are not provided a detailed description of, and other factors such as;
      effect on the environment, risk of simultaneous requirements of the HEMS
      helicopter with possible negative effect for the patient who most needs it,
      likelihood of accidents with associated negative effect are neither included in
      the cost-benefit analysis. CONCLUSION: Alternations to the working and resting
      periods for Norwegian HEMS operations that will result in a change from the
      current 24-h, continuous emergency readiness with the same crew, to a set-up with
      two, and up to three, different crews are not found to be socio-economically
      beneficial.

PMID- 30241545
TI  - Nodal failure patterns and utility of elective nodal irradiation in submandibular
      gland carcinoma treated with postoperative radiotherapy - a multicenter
      experience.
AB  - BACKGROUND: The patterns of nodal relapse in submandibular gland carcinoma (SMGC)
      patients treated with postoperative radiotherapy (PORT) remain unclear. This
      study aims to investigate the nodal failure patterns and the utility of elective
      nodal irradiation (ENI) in SMGC patients undergoing PORT. METHODS: We
      retrospectively enrolled 65 SMGC patients who underwent PORT between 2000 and
      2014. The nodal failure sites in relation to irradiation fields and pathological
      parameters were analyzed. ENI regions were categorized into three bilateral
      echelons (first, levels I-II; second, level III; and third, levels IV-V).
      Extended ENI was defined as coverage of at least the immediately adjacent
      uninvolved echelons bilaterally; otherwise, limited ENI was administered.
      RESULTS: Thirty patients (46%) were stage III-IV, and 18 (28%) were pN+. Neck
      irradiation included limited (72%) and extended ENI (28%). With a median follow
      up of 79 months, 11 patients (17%) developed nodal failures (ipsilateral, N = 6;
      contralateral, N = 7), 7 (64%) of whom relapsed in the adjacent uninvolved
      echelons. We identified pN+ (P = 0.030), extranodal extension (ENE, P = 0.002),
      pT3-4 (P = 0.021), and lymphovascular invasion (LVI, P = 0.004) as significant
      predictors of contralateral neck recurrence. Extended ENI significantly improved
      regional control (RC) in patients with pN+ (P = 0.003), ENE (P = 0.022), pT3-4 (P
      = 0.044), and LVI (P = 0.014), and improved disease-free survival (DFS) in
      patients with pN+ (P = 0.034). For patients with >=2 coincident adverse factors,
      extended ENI significantly increased RC (P < 0.001), distant metastasis-free
      survival (P = 0.019), and DFS (P = 0.007); conversely, no nodal recurrence was
      observed in patients without these adverse factors, even when only the involved
      echelon was irradiated. CONCLUSIONS: Nodal failure is not uncommon in SMGC
      patients treated with PORT if pN+, ENE, pT3-4, and LVI are present. Extended ENI
      should be considered, particularly in patients with multiple pathological adverse
      factors.

PMID- 30241546
TI  - The housing first technical assistance and training (HFTAT) implementation
      strategy: outcomes from a mixed methods study of three programs.
AB  - BACKGROUND: This paper discusses the initial testing of the Housing First
      Training and Technical Assistance (HFTAT) Program, a multifaceted, distance-based
      strategy for the implementation of the Housing First (HF) supportive housing
      model. HF is a complex housing intervention for serving people living with
      serious mental illness and a substance use disorder that requires significant
      individual- and structural-level changes to implement. As such, the HFTAT employs
      a combined training and consultation approach to target different levels of the
      organization. Training delivered to all organizational staff focuses on building
      individual knowledge and uses narrative storytelling to overcome attitudinal
      implementation barriers. Consultation seeks to build skills through technical
      assistance and fidelity audit and feedback. METHOD: We employed a mixed method
      design to understand both individual-level (e.g., satisfaction with the HFTAT, HF
      knowledge acquisition and retention, and HF acceptability and appropriateness)
      and structural-level (e.g., fidelity) outcomes. Quantitative data were collected
      at various time points, and qualitative data were collected at the end of HFTAT
      activities. Staff and administrators (n = 113) from three programs across three
      states participated in the study. RESULTS: Satisfaction with both training and
      consultation was high, and discussions demonstrated both activities were
      necessary. Flexibility of training modality and narrative storytelling were
      particular strengths, while digital badging and the community of practice were
      perceived as less valuable because of incompatibilities with the work context. HF
      knowledge was high post training and retained after 3-month follow-up.
      Participants reported training helped them better understand the model. Attitudes
      toward evidence-based interventions improved over 6 months, with qualitative data
      supporting this but demonstrating some minor concerns related to acceptability
      and appropriateness. Fidelity scores for all programs improved over 9 months.
      CONCLUSION: The HFTAT was a well-liked and generally useful implementation
      strategy. Results support prior research pointing to the value of both (a)
      multifaceted strategies and (b) combined training and consultation approaches.
      The study also provides evidence for narrative storytelling as an approach for
      changing attitudinal implementation barriers. The need for compatibility between
      specific elements of an implementation strategy and the work environment was also
      observed.

PMID- 30241547
TI  - Depressive symptoms are associated with a functional polymorphism in a miR-433
      binding site in the FGF20 gene.
AB  - Genetic studies of major depressive disorder and its associated endophenotypes
      are useful for the identification of candidate genes. In recent years, variations
      in non-coding RNA genes, such as miRNAs, have been explored as novel candidates
      for psychiatric disorders and related endophenotypes. The aim of the present
      study was to evaluate the possible association between a functional polymorphism
      (rs12720208) in the FGF20 gene, which regulates its modulation by miR-433, and
      depressive symptoms in young adults. A sample of 270 participants from Colombia
      were evaluated with the Hospital Anxiety and Depression Scale - Depression
      Subscale (HADS-D) and genotyped for the rs12720208 polymorphism using a TaqMan
      assay. A lineal regression analysis was used. A statistically significant
      association of the functional polymorphism in the FGF20 gene (rs12720208) with
      depressive symptoms was found. It was observed that individuals with the G/A
      genotype had higher scores for the HADS-D subscale. Our results are the first
      description in the scientific literature about a significant association between
      a functional polymorphism in the FGF20 gene, which regulates its modulation by
      miR-433, and depressive symptoms.

PMID- 30241548
TI  - Reduced synaptic function of Kainate receptors in the insular cortex of Fmr1
      Knock-out mice.
AB  - Fragile X syndrome is caused by the loss of fragile X mental retardation protein
      (FMRP). Kainate receptor (KAR) is a subfamily of ionotropic glutamate receptors
      (iGluR) that acts mainly as a neuromodulator of synaptic transmission and
      neuronal excitability. However, little is known about the changes of synaptic KAR
      in the cortical area of Fmr1 KO mice. In this study, we performed whole-cell
      patch-clamp recordings from layer II/III pyramidal neurons in the insular cortex
      of Fmr1 KO mice. We found that KARs mediated currents were reduced in Fmr1 KO
      mice. KARs were mainly located in the synaptosomal fraction of the insular
      cortex. The abundance of KAR subunit GluK1 and GluK2/3 in the synaptosome was
      reduced in Fmr1 KO mice, whereas the total expressions of these KARs subunits
      were not changed. Finally, lack of FMRP impairs subsequent internalization of
      surface GluK2 after KAR activation, while having no effect on the surface GluK2
      expression. Our studies provide evidence indicating that loss of FMRP leads to
      the abnormal function and localization of KARs. This finding implies a new
      molecular mechanism for Fragile X syndrome.

PMID- 30241550
TI  - High hepatic macrophage activation and low liver function in stable Wilson
      patients - a Danish cross-sectional study.
AB  - BACKGROUND: Hepatic macrophage (Kupffer cell) hyperplasia is often described in
      Wilson's disease (WD). In many liver diseases, Kupffer cell activation is related
      to disease severity, liver function, and fibrosis but the importance in WD is
      unknown. Kupffer cell activation can be assessed by the P-concentration of
      soluble (s)CD163, metabolic liver function by the galactose elimination capacity
      (GEC), and fibrosis by Fibroscan. We investigated the associations between
      sCD163, selected inflammatory cytokines, GEC, and liver fibrosis in Danish WD
      patients. METHODS: In a cross-sectional design, we studied 29 stable and well
      treated patients (male/female15/14) with a median age of 35 years (IQR 24-50). P
      sCD163 and cytokines were measured by ELISA. The GEC was measured by intra-venous
      galactose loading. RESULTS: The median P-sCD163 value at 2.96 mg/L (1.97-3.93)
      was high in the normal range (0.7-3.9) and seven patients (24%) had a value above
      the upper normal value. sCD163 correlated with TNF-alpha, IL-6 and IL-8 (rho>
      0.50, p < 0.005). A higher sCD163 value was closely associated with a lower GEC
      (rho = - 0.51, p = 0.02). sCD163 was not related to the liver fibrosis indices.
      CONCLUSIONS: Stable WD patients showed various degrees of Kupffer cell activation
      which was accompanied by loss of metabolic liver function. Neither activation nor
      liver function was related to liver fibrosis. The findings suggest that in WD
      inflammatory Kupffer cell activation may be involved in the loss of liver
      function over time. sCD163 may serve as a non-invasive biomarker of loss of liver
      function in WD, which the degree of fibrosis evidently may not. This study is
      registered at clinical trials with name: "sCD163 and sMR in Wilsons Disease -
      Associations With Disease Severity and Fibrosis", NCT02702765. Date of
      registration: 26.02.16. Date of enrolment of the first participant to the trial:
      17.03.16. ULR: https://clinicaltrials.gov/ct2/show/NCT02702765 .

PMID- 30241551
TI  - Efficacy of sirolimus for the prevention of recurrent pneumothorax in patients
      with lymphangioleiomyomatosis: a case series.
AB  - Pneumothorax is one of the most common symptoms in patients with
      lymphangioleiomyomatosis (LAM). However, current management strategies for
      patients with LAM who present with recurrent pneumothorax remain inadequate.
      Here, we describe the successful prevention of recurrent pneumothorax by
      sirolimus treatment in five women with LAM. Before sirolimus treatment, all
      patients had received supplemental oxygen support, repeated chest tube drainage,
      or surgeries for management of the recurrent pneumothorax. Sirolimus treatment
      was initiated when the pneumothorax was completely resolved, and no patient
      developed pneumothorax during treatment. Moreover, they exhibited a significantly
      improved subjective quality of life, increased exercise capacity, and mild
      adverse effects such as mucositis, irregular menstruation, and delayed wound
      healing. On discontinuation of sirolimus or in the event that the plasma
      sirolimus level was markedly low, pneumothorax tended to relapse. The findings
      from these cases provide valuable insights that will aid in the improvement of
      treatment strategies for patients with LAM and recurrent pneumothorax.

PMID- 30241549
TI  - The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully
      immunocompetent mouse model.
AB  - BACKGROUND: The L-type amino acid transporter 1 (LAT1/SLC7A5) transports
      essential amino acids across the plasma membrane. While LAT1 is overexpressed in
      a variety of human neoplasms, its expression and its role in thyroid cancer is
      currently unknown. Anaplastic thyroid carcinoma (ATC) is a highly aggressive
      malignancy for which no effective therapy exists. The purpose of this study was
      to explore whether the inhibition of LAT1 in ATC would affect tumor growth both
      in vitro and in vivo. METHODS: LAT1 was pharmacologically blocked by JPH203 in
      human ATC and papillary thyroid cancer (PTC) cell lines. The effects on
      proliferation and mTORC1 activity were addressed in vitro. A genetically
      engineered mouse model of ATC was used to address the effect of blocking LAT1 on
      tumor growth in vivo. SLC7A5 transcription was measured in patient-derived ATC
      samples to address the clinical relevance of the findings. RESULTS: LAT1 block by
      JPH203 reduced proliferation and mTORC1 signaling in human thyroid cancer cell
      lines. SLC7A5 transcription was upregulated in ATC tissues derived from a
      genetically engineered mouse model and in ATC samples recovered from patients.
      JPH203 treatment induced thyroid tumor growth arrest in vivo in a fully
      immunocompetent mouse model of thyroid cancer. Additionally, analysis of publicly
      available datasets of thyroid carcinomas revealed that high LAT1 expression is
      associated with potentially untreatable PTC presenting reduced NIS/SLC5A5
      transcription and with ATC. CONCLUSIONS: These preclinical results show that LAT1
      inhibition is a novel therapeutic approach in the context of thyroid cancers, and
      more interestingly in untreatable thyroid cancers.

PMID- 30241552
TI  - Gonadotropin and steroid hormones regulate pluripotent very small embryonic-like
      stem cells in adult mouse uterine endometrium.
AB  - BACKGROUND: Very small embryonic-like stem cells (VSELs) exist in adult organs,
      express pluripotent markers and have the ability to differentiate into three germ
      layers in vitro. Testicular, ovarian and hematopoietic stem/progenitor cells
      express receptors for follicle stimulating (FSH) and ovarian hormones and are
      activated by them to undergo proliferation/differentiation. VSELs exist in mouse
      uterus and are regulated by physiological dose of estradiol (E) & progesterone
      (P) during endometrial growth, differentiation and regeneration/remodeling. In
      the present study, effects of daily administration of E (2 MUg/day), P (1
      mg/Kg/day) or FSH (5 IU/day) for 7 days on the endometrium and stem/progenitor
      cells was studied in bilaterally ovariectomized mice. RESULTS: E treatment
      resulted in hypertrophy whereas P resulted in hyperplasia and overcrowding of
      epithelial cells. FSH also directly stimulated the endometrial cells. Nuclear OCT
      4A positive VSELs were visualized in ovariectomized (atrophied) endometrium and
      cytoplasmic OCT-4B positive epithelial, stromal and endothelial cells were
      observed after treatment. FSH treated uterine tissue showed presence of 4
      alternately spliced FSHR isoforms by Western blotting. 3-5 MUm VSELs with a
      surface phenotype of LIN-/CD45-/SCA-1+ were enumerated by flow cytometry and were
      found to express ER, PR, FSHR1 and FSHR3 by RT-PCR analysis. Differential effects
      of treatment were observed on pluripotent (Oct4A, Sox2, Nanog), progenitors (Oct
      4, Sca-1), primordial germ cells (Stella, Fragilis) and proliferation (Pcna)
      specific transcripts by qRT-PCR analysis. FSH and P (rather than E) exerted
      profound, direct stimulatory effects on uterine VSELs. Asymmetric, symmetric
      divisions and clonal expansion of stem/progenitor cells was confirmed by co
      expression of OCT-4 and NUMB. CONCLUSIONS: Results confirm presence of VSELs and
      their regulation by circulatory hormones in mouse uterus. Stem cell activation
      was more prominent after P and FSH compared to E treatment. The results question
      whether epithelial cells proliferation is regulated by paracrine influence of
      stromal cells or due to direct action of hormones on stem cells. VSELs expressing
      nuclear OCT-4A are the most primitive and pluripotent stem cells, undergo
      asymmetric cell division to self-renew and differentiate into epithelial, stromal
      and endothelial cells with cytoplasmic OCT-4B. Role of follicle stimulating and
      steroid hormones on the stem cells needs to be studied in various uterine
      pathologies.

PMID- 30241554
TI  - Assessment of Prostaglandin-Endoperoxide Synthase 2 and Versican gene expression
      profile from the cumulus cells: association with better in vitro fertilization
      outcomes.
AB  - BACKGROUND: Current methods for determining superior embryo quality
      (morphological assessment) are unable to compensate for poor pregnancy outcomes.
      Due to the importance of the cumulus-oocyte complex and the value of cumulus
      cells (CCs) as markers of embryo health, we determined the association between
      the CCs gene expression of the Prostaglandin-Endoperoxide Synthase 2 (PTGS2) and
      Versican (VCAN) with pregnancy. METHODS: One hundred forty-nine women, suffering
      from infertility and undergoing IVF, were included in this study (age: 29-46
      years; BMI = 25.5 +/- 5.0 kg/m2). Patients underwent a standard IVF protocol. CCs
      were isolated during oocyte retrieval, and their RNA was isolated using Trizol.
      The mRNA expression of PTGS2, VCAN, and L19 was measured by qPCR. The PVL index,
      (PTGS2 + VCAN)*L19normalized, was determined for each oocyte. Clinical pregnancy
      was confirmed by beta-hCG and the presence of a fetal heartbeat. Associations
      were determined by ROC curves or logistic regression. RESULTS: There was no
      correlation between the PVL index and morphological scores. Using only single
      embryo transfers (SETs), we determined that the PVL index was associated with
      pregnancy (beta-hCG: AUC = 0.87, 95%CI: 0.74-1.00) with an optimal cutoff value
      of 58.2. Using the complete cohort (consisting of SETs, and patients with 2, 3,
      or 4 embryos transferred), the presence of at least one embryo with a PVL index
      score >= 58.2 was associated with a greater probability of achieving pregnancy
      (beta-hCG: odds ratio = 17.15, 95%CI: 6.82-43.18, p < 0.001). CONCLUSION:
      Transferring at least one embryo with a PVL index score >= 58.2, generates a
      higher chance of achieving pregnancy.

PMID- 30241555
TI  - Correction to: Effect of radiochemotherapy on T2* MRI in HNSCC and its relation
      to FMISO PET derived hypoxia and FDG PET.
AB  - Following the publication of this article [1], the authors noticed that figures
      2, 3, 4 and 5 were in the incorrect order and thus had incorrect captions.

PMID- 30241553
TI  - miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the
      TGFbeta pathway.
AB  - BACKGROUND: We previously reported that miR-203 functions as a tumor suppressor
      in ovarian cancer cells by directly targeting transcription factor Snai2 and
      inhibiting epithelial to mesenchymal transition (EMT), whereas BIRC5/survivin
      promotes EMT. In this study, we tested our hypothesis that miR-203 inhibits
      ovarian tumor metastasis by suppressing EMT through targeting BIRC5, using an
      orthotopic ovarian cancer mouse model. METHODS: We overexpressed miR-203 in
      ovarian cancer SKOV3 and OVCAR3 cells using a lentiviral vector and examined cell
      migration and invasion using transwell plates. The small molecule inhibitor,
      YM155, was used to inhibit survivin expression. miR-203-expressing and control
      SKOV3 cells were intrabursally injected into immunocompromised NSG female mice.
      Primary tumors in ovaries and metastatic tumors were collected to determine the
      expression of survivin and EMT markers using Western blot and immunostaining.
      RESULTS: Overexpression of miR-203 inhibits EMT by targeting BIRC5 in ovarian
      cancer SKOV3 and OVCAR3 cells. miR-203 expression enhances the ability of the
      survivin inhibitor YM155 to reduce tumor cell migration and invasion in vitro. We
      further showed that miR-203 expression attenuated the TGFbeta pathway in both
      SKOV3 and OVCAR3 cells. miR-203 expression also inhibited primary tumor growth in
      ovaries and metastatic tumors in multiple peritoneal organs including liver and
      spleen. CONCLUSION: miR-203 inhibits ovarian tumor metastasis by targeting
      BIRC5/survivin and attenuating the TGFbeta pathway.

PMID- 30241556
TI  - Worth a local treatment? - Analysis of modern radiotherapy concepts for
      oligometastatic prostate cancer.
AB  - BACKGROUND: Prostate cancer (PCA) is the most-prevalent non-skin cancer in men
      worldwide. Nevertheless, the treatment of oligometastatic, especially lymph-node
      (ln) recurrent, PCA remains elusive. The aim of our study was to provide insights
      in radiotherapy (RT)-treatment of recurrent PCA exhibiting ln- or osseous (oss)
      oligometastases. METHODS: Between April 2012 and April 2017, 27 oligometastatic
      PCA patients (19 ln and 8 single oss) were treated with RT at our institution.
      RESULTS: The metastasis-free survival (MFS) was 24.8 m (22.0-36.0 m) and 25.4 m
      (23.9-28.1 m) for the ln- and oss-subgroup resulting in 1-year MFS of 75.4 and
      100% and 2-year MFS of 58.7 and 83.3% for ln- and oss-metastatic patients,
      respectively. Of notice, none of the recurrences for ln-patients was in the RT
      field, constituting a local control of 100%. Within the ln-group, pre-RT median
      PSA was 2.6 ng/ml, median post-RT PSA was 0.3 ng/ml, which was significant (p =
      0.003). Median biochemical-free survival (bfS) was 12.2 m. PCA that was initially
      confined to the prostate had a better bfS (p < 0.001) and MFS (p = 0.013). The
      oss-group had a median PSA of 4.9 ng/ml pre-treatment which dropped to a median
      value of 0.14 ng/ml (p = 0.004). Toxicities were moderate, with only 1 case of
      III degrees  toxicity. There were no deaths in the ln-group, thus overall survial
      was 100% here. CONCLUSION: Our study points out the feasibility of RT as a
      treatment option in recurrent PCA and demonstrates an excellent local control
      with a low-toxicity profile.

PMID- 30241557
TI  - Are healthcare professionals delivering opportunistic behaviour change
      interventions? A multi-professional survey of engagement with public health
      policy.
AB  - BACKGROUND: "Making Every Contact Count" (MECC), a public health policy in the
      UK, compels healthcare professionals to deliver opportunistic health behaviour
      change interventions to patients during routine medical consultations.
      Professionals' awareness of, and engagement with, the policy is unclear. This
      study examined (1) awareness of the MECC policy, and (2) the prevalence of MECC
      related practice in relation to (a) perceived patient benefit, (b) how often
      healthcare professionals deliver interventions during routine consultations, and
      (c) the time spent on this activity. METHODS: Cross-sectional national survey was
      administered in 2017 of 1387 healthcare professionals working in the UK's
      National Health Service (NHS). Descriptive statistics were used to assess
      awareness and practice consistent with the MECC policy. Chi-square was used to
      gauge the potential representativeness of our sample compared to NHS employment
      data. RESULTS: 31.4% of healthcare professionals reported having heard of the
      policy; nevertheless, healthcare professionals perceived a need to provide
      patients with opportunistic behaviour change interventions in 55.9%
      (32,946/58,906) of consultations. However, healthcare professionals did not
      deliver interventions on 50.0% of occasions in which they perceived a need. Where
      behaviour change interventions were delivered to patients, this constituted 35.3%
      of the appointment time. CONCLUSIONS: Policy makers must address the gap between
      the proportion of patients that healthcare professionals perceive would benefit
      from opportunistic behaviour change interventions and those receiving them (an
      estimated 50.0%; 16,473 additional patients could have benefited). Future
      research should consider how healthcare professionals identify patients who might
      benefit from opportunistic behaviour change interventions and developing training
      for efficient delivery of interventions.

PMID- 30241558
TI  - Effects of repurposed drug candidates nitroxoline and nelfinavir as single agents
      or in combination with erlotinib in pancreatic cancer cells.
AB  - BACKGROUND: Pancreatic cancer (PC) is the fourth most common cause of cancer
      death. Combination therapies with classical chemotherapeutic agents improved
      treatment of advanced PC at the cost of a relevant toxicity, but the 5-year
      survival rate remains below 5%. Consequently, new therapeutic options for this
      disease are urgently needed. In this study, we explored the effect of two
      repurposed drug candidates nelfinavir and nitroxoline, approved for non
      anticancer human use, in PC cell lines. Nelfinavir and nitroxoline were tested as
      single agents, or in combinations with or without erlotinib, a targeted drug
      approved for PC treatment. METHODS: The effects of the drugs on the viability of
      AsPC-1, Capan-2 and BxPC-3 PC cell lines were assessed by MTT. The impact of the
      treatments on cell cycle distribution and apoptosis was analyzed by flow
      cytometry. The effects of treatments on proteins relevant in cell cycle
      regulation and apoptosis were evaluated by western blot. Self-renewal capacity of
      PC cell lines after drug treatments was assessed using a clonogenic assay.
      RESULTS: When used as single agents, nelfinavir and nitroxoline decreased
      viability, affected cell cycle and reduced the expression of relevant cell cycle
      proteins. The effects on apoptosis were variable among PC cell lines. Moreover,
      these agents drastically impaired clonogenic activity of the three PC cell lines.
      Combinations of nelfinavir and nitroxoline, with or without erlotinib, resulted
      in dose- and cell-dependent synergistic effects on cell viability. These effects
      were paralleled by cell cycle alterations and more consistent apoptosis induction
      as compared to single agents. Treatments with drug combinations induced drastic
      impairment of clonogenic activity in the three cell lines. CONCLUSIONS: This
      study shows that two non-antitumor drugs, nelfinavir and nitroxoline, as single
      agents or in combination have antitumor effects that appear comparable, or in
      some case more pronounced than those of erlotinib in three PC cell lines. Our
      results support repurposing of these approved drugs as single agents or in
      combination for PC treatment.

PMID- 30241559
TI  - Impact of drug and equipment preparation on pre-hospital emergency Anaesthesia
      (PHEA) procedural time, error rate and cognitive load.
AB  - BACKGROUND: We examined the effect of advanced preparation and organisation of
      equipment and drugs for Pre-hospital Emergency Anaesthesia (PHEA) and tracheal
      intubation on procedural time, error rates, and cognitive load. METHODS: This
      study was a randomised, controlled experiment with a crossover design. Clinical
      teams (physician and paramedic) from the Emergency Medical Retrieval Service and
      the Scottish Air Ambulance Division were randomised to perform a standardised pre
      hospital clinical simulation using either unprepared (standard practice) or pre
      prepared (experimental method) PHEA equipment and drugs. Following a two-week
      washout period, each team performed the corresponding simulation. The primary
      outcome was intervention time. Secondary outcomes were safety-related incidents
      and errors, and degree of cognitive load. RESULTS: In total 23 experiments were
      completed, 12 using experimental method and 11 using standard practice. Time
      required to perform PHEA using the experimental method was significantly shorter
      than with standard practice (11,45 versus 20:59) minutes: seconds; p = < 0.001).
      The experimental method also significantly reduced procedural errors (0 versus 9,
      p = 0.007) and the cognitive load experienced by the intubator assistant (41.9
      versus 68.7 mm, p = 0.006). CONCLUSIONS: Pre-preparation of PHEA equipment and
      drugs resulted in safer performance of PHEA and has the potential to reduce on
      scene time by up to a third.

PMID- 30241560
TI  - Is pre-Darwinian evolution plausible?
AB  - BACKGROUND: This essay highlights critical aspects of the plausibility of pre
      Darwinian evolution. It is based on a critical review of some better-known open,
      far-from-equilibrium system-based scenarios supposed to explain processes that
      took place before Darwinian evolution had emerged and that resulted in the origin
      of the first systems capable of Darwinian evolution. The researchers' responses
      to eight crucial questions are reviewed. The majority of the researchers claim
      that there would have been an evolutionary continuity between chemistry and
      "biology". A key question is how did this evolution begin before Darwinian
      evolution had begun? In other words the question is whether pre-Darwinian
      evolution is plausible. RESULTS: Strengths and weaknesses of the reviewed
      scenarios are presented. They are distinguished between metabolism-first,
      replicator-first and combined metabolism-replicator models. The metabolism-first
      scenarios show major issues, the worst concerns heredity and chirality. Although
      the replicator-first scenarios answer the heredity question they have their own
      problems, notably chirality. Among the reviewed combined metabolism-replicator
      models, one shows the fewest issues. In particular, it seems to answer the chiral
      question, and eventually implies Darwinian evolution from the very beginning. Its
      main hypothesis needs to be validated with experimental data. CONCLUSION: From
      this critical review it is that the concept of "pre-Darwinian evolution" appears
      questionable, in particular because it is unlikely if not impossible that any
      evolution in complexity over time may work without multiplication and
      heritability allowing the emergence of genetically and ecologically diverse
      lineages on which natural selection may operate. Only Darwinian evolution could
      have led to such an evolution. Thus, Pre-Darwinian evolution is not plausible
      according to the author. Surely, the answer to the question posed in the title is
      a prerequisite to the understanding of the origin of Darwinian evolution.
      REVIEWERS: This article was reviewed by Purificacion Lopez-Garcia, Anthony Poole,
      Doron Lancet, and Thomas Dandekar.

PMID- 30241561
TI  - A double blind randomised control trial investigating the efficacy of platelet
      rich plasma versus placebo for the treatment of greater trochanteric pain
      syndrome (the HIPPO trial): a protocol for a randomised clinical trial.
AB  - BACKGROUND: Greater trochanteric pain syndrome (GTPS) is a painful condition
      characterised by pain around the greater trochanter usually affecting middle-aged
      women. The majority of patients will improve with conservative management such as
      physiotherapy and non-steroidal anti-inflammatory drugs (NSAIDs); however, if
      this fails then more invasive treatments including corticosteroid injections and
      surgery may be required. Platelet-rich plasma (PRP) is an autologous blood
      product, which has a higher concentration of growth factors postulated to provide
      enhanced healing and anti-inflammatory properties. There have been numerous
      studies on PRP's efficacy in musculoskeletal soft tissue conditions with similar
      pathology to GTPS, with varying results, most promising being in plantar
      fasciopathy and patellar tendinopathy. Corticosteroids are the established second
      line treatment, but do not always work long term. PRP may be a suitable
      alternative to corticosteroid in GTPS with longer-term effects; however, there
      are very limited reports. The Hip Injections PRP Vs Placebo (HIPPO) trial aims to
      assess the ability of PRP to improve symptoms and function in patients with GTPS.
      METHODS/DESIGN: HIPPO is a single-centre, double-blind randomized placebo
      controlled study in patients with a radiologically confirmed diagnosis of gluteus
      medius or minimus tendinopathy with swelling within the tendon insertion with or
      without bursitis. We aim to randomise 102 patients with GTPS to either the PRP or
      placebo (normal saline injection) treatment arm. Participants will receive one
      ultrasound (US) guided PRP/placebo injection into the trochanteric bursa and
      surrounding gluteus medius/minimus tendons. The primary outcome measure is the
      International Hip Outcome Tool-12. Secondary outcome measures will include a
      visual analogue score for pain, the three-level version of the EuroQol five
      dimensional questionnaire and the modified Harris Hip Score. Outcomes will be
      measured at baseline, 3, 6 and 12 months. Participants will have the option at 6
      months to have a repeat blinded injection or cross over to PRP. Analyses of
      primary and secondary outcomes will be made according to the intention-to-treat
      principle. The trial reporting will comply with Consolidated Standards of
      Reporting Trials (CONSORT) guidelines. DISCUSSION: The HIPPO study has been
      designed to test the hypothesis that PRP is effective in treating GTPS in
      patients who have failed conservative management and to assess the duration of
      effect of PRP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03479190 . Registered
      on 27 March 2018.

PMID- 30241562
TI  - Xue-Fu-Zhu-Yu capsule in the treatment of qi stagnation and blood stasis
      syndrome: a study protocol for a randomised controlled pilot and feasibility
      trial.
AB  - BACKGROUND: Qi stagnation and blood stasis syndrome (QS&BSS) is one of the common
      Zhengs in traditional Chinese medicine (TCM), which manifests as various symptoms
      and signs, such as distending pain or a tingling sensation in a fixed position.
      In recent years, a number of clinical trials have focused on the effectiveness
      and safety of XFZYC in patients with a QS&BSS subtype disease, such as coronary
      heart disease, hyperlipidaemia, ischaemic cerebrovascular disease, gastritis,
      dysmenorrhoea, or arthritis, in terms of the outcomes of relevant diseases.
      However, there is lack of evidence of the effects of XFZYC in patients with
      QS&BSS with different diseases, focusing on the outcomes of Zhengs.
      METHODS/DESIGN: A randomised, controlled, pilot and feasibility trial will be
      employed in this study, using a 7-week study period. Participants will be
      recruited from Guang'anmen Hospital, Huguosi TCM Hospital, Wangjing Hospital in
      China. One hundred and twenty participants will be randomised to a treatment
      group (Xue-Fu-Zhu-Yu Capsule (XFZYC)) and placebo group in a 1:1 ratio.
      Participants included in the study must be diagnosed with Qi stagnation and blood
      stasis syndrome criteria. The outcome measurements will include the traditional
      Chinese medicine patient-reported outcome (PRO) scale for QS&BSS, the single
      symptom and sign scale of QS&BSS, and the pain scale of QS&BSS. The clinical data
      management system ( http://www.tcmcec.net /) will be used to collect and manage
      the data. Quality control will be used, according to Good Clinical Practice
      (GCP). DISCUSSION: Previous studies were expected to evaluate whether the
      addition of XFZYC to standard routine treatment would enhance the treatment
      effectiveness and improve the biomedical parameters pertaining to relevant
      disease. However, this trial is focused on the outcome of Zhengs, and we chose a
      range of outcome measurements to assess the improvement of relevant symptoms and
      signs. This trial is the first study designed to define and optimise the outcome
      measurements of Zhengs of XFZYC in the treatment of patients with QS&BSS. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT03091634 . Registered on 12 August 2018.
      Release date 6 May 2017.

PMID- 30241563
TI  - Physicians' utilization of microbiologic reports and determinants of their
      preference to order culture in Tikur Anbessa Specialized Hospital, Addis Ababa,
      Ethiopia.
AB  - OBJECTIVE: The main aim of the study was to assess physicians' utilization of
      microbiologic reports and determinants of their preference in ordering
      microbiologic culture among patients with systemic bacterial infection at Tikur
      Anbessa Specialized Hospital. RESULTS: Of the total 369 patients observed, 91
      (24.7%) had microbiologic reports (culture and gram stain). About 12% of the
      patients had culture reports of which majority (77.8%) were available after 72 h
      of the initial antibiotic start. Antimicrobial susceptibility test was done for
      83.3% of the positive cultures. Although 99.5% of the patients were initially
      placed on empiric therapy, adjustment was done in 114 (30.9%) of the patients.
      Among these patients with adjusted therapy, changes were unrelated to
      microbiologic reasons in 103 (90.4%) patients. None of these changes were for the
      reason of streamlining therapy. Prolonged hospital stay (AOR = 2.9, 95% CI 1.2
      6.7), senior physician consultation (AOR = 4.1, 95% CI 1.1-17.7) and suspicion of
      new site of infection (AOR = 2.6, 95% CI 1.1-6.2) were positive independent
      predictors for physicians' preference in ordering culture.

PMID- 30241564
TI  - Effect of persuasive messages on National Health Service Organ Donor
      Registrations: a pragmatic quasi-randomised controlled trial with one million UK
      road taxpayers.
AB  - BACKGROUND: A shortage of organs available for transplantation is causing loss of
      life. Increasing the number of individuals on the National Health Service (NHS)
      Organ Donor Register (ODR) is one way to address the shortage of organs. In Great
      Britain, new drivers registering for their driving licence are invited to join
      the ODR. A further 17 million drivers renew their road tax online each year,
      presenting an additional opportunity to prompt drivers to join the ODR. This
      trial explores the effect of adding persuasive messages to a prompt to join the
      ODR at the end of road tax payment transactions. METHODS: In this pragmatic,
      parallel group, quasi-randomised controlled trial, drivers renewing their road
      tax or registering for a driving licence were alternately allocated, using a
      JavaScript randomisation code embedded in the GOV.UK website, to view a control
      prompt inviting sign-ups to the ODR or the same prompt plus one of seven
      theoretically informed persuasive messages; (i) social norms alone, (ii) social
      norms plus the NHS ODR logo, (iii) social norms plus an image, (iv) loss frame,
      (v) gain frame, (vi) reciprocity and (vii) cognitive dissonance. The trial took
      place over a 4-week period in June 2013. The primary outcome measure was
      participants completing the online registration form (sign-ups). RESULTS:
      Altogether, 1,085,322 website users were included in the study. Further, 1171
      more sign-ups were completed under the most effective message (reciprocity)
      compared to the control prompt alone (reciprocity: n = 4256, control: n = 3085;
      odds ratio, OR 1.38, 95% confidence interval 1.32-1.45, p < 0.001). The loss
      framed message was as effective. All messages increased sign-ups compared to the
      control prompt apart from the social norms message plus image (n = 2879; OR 0.94,
      95% confidence interval 0.89-0.99, p < 0.05). CONCLUSIONS: Short persuasive
      messages alongside a prompt can persuade more ODR sign-ups for individuals
      renewing their road tax than a prompt alone. The most effective message remains
      in place today. Since the trial in 2013, the same message has been implemented
      across 25 government end-of-transaction websites on GOV.UK, resulting in 529,000
      new registrations to the ODR up to 31st October 2017.

PMID- 30241565
TI  - Comparison of low calorie high protein and low calorie standard protein diet on
      waist circumference of adults with visceral obesity and weight cycling.
AB  - OBJECTIVES: Many individuals with visceral obesity who previously had succeeded
      in reducing body weight regain and this loss-gain cycle repeats several times
      which is called as weight cycling. We aimed to evaluate the effect of a low
      calorie high protein diet (HP) compared to a low calorie standard protein diet
      (SP) on waist circumference of visceral obese adults with history of weight
      cycling. RESULTS: In this open-randomized clinical trial, participants were asked
      to follow dietary plan with reduction in daily caloric intake ranging from 500 to
      1000 kcal from usual daily amount with minimum daily amount of 1000 kcal for 8
      weeks and were divided in two groups: HP group with protein as 22-30% total
      calorie intake; and SP group with protein as 12-20% total calorie intake. There
      was a statistically significant difference (P < 0.001) between waist
      circumference before and after the dietary intervention among both groups.
      Meanwhile, there was no statistically significant difference in the mean
      reduction of waist circumference between HP and SP groups (P = 0.073). Taken
      together, the protein proportion does not significantly affected waist
      circumference. Trial registration ClinicalTrials.gov NCT03374150, 11 December
      2017.

PMID- 30241566
TI  - Analysis of peptide-SLA binding by establishing immortalized porcine alveolar
      macrophage cells with different SLA class II haplotypes.
AB  - Primary porcine alveolar macrophages (PAM) are useful for studying viral
      infections and immune response in pigs; however, long-term use of these cells is
      limited by the cells' short lifespan. We immortalized primary PAMs by
      transfecting them with both hTERT and SV40LT and established two immortalized
      cell lines (iPAMs) actively proliferating even after 35 passages. These cells
      possessed the characteristics of primary PAMs, including strong expression of
      swine leukocyte antigen (SLA) class II genes and the inability to grow anchorage
      independently. We characterized their SLA genes and subsequently performed
      peptide-SLA binding assays using a peptide from porcine circovirus type 2 open
      reading frame 2 to experimentally measure the binding affinity of the peptide to
      SLA class II. The number of peptides bound to cells measured by fluorescence was
      very low for PK15 cells (7.0% +/- 1.5), which are not antigen-presenting cells,
      unlike iPAM61 (33.7% +/- 3.4; SLA-DQA*0201/0303, DQB1*0201/0901, DRB1*0201/1301)
      and iPAM303 (73.3% +/- 5.4; SLA DQA*0106/0201, DQB1*0202/0701, DRB1*0402/0602).
      The difference in peptide binding between the two iPAMs was likely due to the
      allelic differences between the SLA class II molecules that were expressed. The
      development of an immortal PAM cell panel harboring diverse SLA haplotypes and
      the use of an established method in this study can become a valuable tool for
      evaluating the interaction between antigenic peptides and SLA molecules and is
      important for many applications in veterinary medicine including vaccine
      development.

PMID- 30241568
TI  - Correction to: Enhancing maternal and infant wellbeing: study protocol for a
      feasibility trial of the Baby Triple P Positive Parenting programme for mothers
      with severe mental health difficulties (the IMAGINE study).
AB  - Following publication of the original article [1], the authors reported that
      Elizabeth Camacho was omitted from the author name list.

PMID- 30241567
TI  - A reverse metabolic approach to weaning: in silico identification of immune
      beneficial infant gut bacteria, mining their metabolism for prebiotic feeds and
      sourcing these feeds in the natural product space.
AB  - BACKGROUND: Weaning is a period of marked physiological change. The introduction
      of solid foods and the changes in milk consumption are accompanied by significant
      gastrointestinal, immune, developmental, and microbial adaptations. Defining a
      reduced number of infections as the desired health benefit for infants around
      weaning, we identified in silico (i.e., by advanced public domain mining) infant
      gut microbes as potential deliverers of this benefit. We then investigated the
      requirements of these bacteria for exogenous metabolites as potential prebiotic
      feeds that were subsequently searched for in the natural product space. RESULTS:
      Using public domain literature mining and an in silico reverse metabolic
      approach, we constructed probiotic-prebiotic-food associations, which can guide
      targeted feeding of immune health-beneficial microbes by weaning food; analyzed
      competition and synergy for (prebiotic) nutrients between selected microbes; and
      translated this information into designing an experimental complementary feed for
      infants enrolled in a pilot clinical trial (
      http://www.nourishtoflourish.auckland.ac.nz/ ). CONCLUSIONS: In this study, we
      applied a benefit-oriented microbiome research strategy for enhanced early-life
      immune health. We extended from "classical" to molecular nutrition aiming to
      identify nutrients, bacteria, and mechanisms that point towards targeted feeding
      to improve immune health in infants around weaning. Here, we present the systems
      biology-based approach we used to inform us on the most promising prebiotic
      combinations known to support growth of beneficial gut bacteria ("probiotics") in
      the infant gut, thereby favorably promoting development of the immune system.

PMID- 30241569
TI  - Migration for obstetric care: the impact of regional Obstetric Care Facility
      Density disparities in Tanzania.
AB  - OBJECTIVE: This is an extended analysis of the previously published data to
      demonstrate the relationship between high Obstetric Care Facility Density (OCFD)
      and migration for obstetric services in Tanzania. RESULTS: Overall, regions with
      excess institutional deliveries had significantly higher OCFD compared to other
      regions. A consistent pattern was observed whereby regions with excess
      Institutional deliveries also exhibited the most outstanding OCFD of all the
      neighbouring regions. The observed patterns of Institutional deliveries and OCFD
      affirm the hypothesis of immigration for obstetric care services from low to high
      OCFD regions. Further research is suggested to prove this hypothesis in the
      field.

PMID- 30241571
TI  - Dermoscopy of skin metastases from breast cancer: two case reports.
AB  - BACKGROUND: Cutaneous metastatic breast cancer is the most common cutaneous
      metastatic malignancy in women. The assessment of cutaneous metastatic disease
      can be perplexing because the clinical presentation appears similar to other skin
      malignancies like angiosarcoma or melanoma, or benign diseases like cellulitis
      and lymphedema. To date, only a limited number of dermoscopic images of cutaneous
      metastatic solid tumors, especially breast cancer, have been published. CASE
      PRESENTATION: The authors report two Moroccan cases highlighting dermoscopy as a
      quick tool to recognize skin metastasis of breast cancer in two different
      clinical presentations. A 51-year-old Moroccan woman presented with nodules of
      various sizes on and around a mastectomy scar, and a 65-year-old Moroccan woman
      presented with cellulitis-like lesions on her chest wall and her back.
      Dermoscopic features were similar in the two cases with findings of yellow
      central areas, polymorphic vessels, whitish bright lines, whitish structureless
      areas, and linear irregular fissure-like depressions on a pink-orange background.
      CONCLUSIONS: The recognition of dermoscopic patterns of cutaneous metastasis of
      breast cancer is not only useful to facilitate diagnosis at an early stage and to
      rule out other differentials, especially in difficult presentations such as
      cellulitis-like lesions or lymphedema, but it may also be used by physicians in
      monitoring mastectomy scars.

PMID- 30241570
TI  - Human chorionic villous mesenchymal stem/stromal cells protect endothelial cells
      from injury induced by high level of glucose.
AB  - BACKGROUND: Mesenchymal stem/stromal cells derived from chorionic villi of human
      term placentae (pMSCs) protect human endothelial cells from injury induced by
      hydrogen peroxide (H2O2). In diabetes, elevated levels of glucose
      (hyperglycaemia) induce H2O2 production, which causes the endothelial dysfunction
      that underlies the enhanced immune responses and adverse complications associated
      with diabetes, which leads to thrombosis and atherosclerosis. In this study, we
      examined the ability of pMSCs to protect endothelial cell functions from the
      negative impact of high level of glucose. METHODS: pMSCs isolated from the
      chorionic villi of human term placentae were cultured with endothelial cells
      isolated from human umbilical cord veins in the presence of glucose. Endothelial
      cell functions were then determined. The effect of pMSCs on gene expression in
      glucose-treated endothelial cells was also determined. RESULTS: pMSCs reversed
      the effect of glucose on key endothelial cell functions including proliferation,
      migration, angiogenesis, and permeability. In addition, pMSCs altered the
      expression of many genes that mediate important endothelial cell functions
      including survival, apoptosis, adhesion, permeability, and angiogenesis.
      CONCLUSIONS: This is the first comprehensive study to provide evidence that pMSCs
      protect endothelial cells from glucose-induced damage. Therefore, pMSCs have
      potential therapeutic value as a stem cell-based therapy to repair glucose
      induced vascular injury and prevent the adverse complications associated with
      diabetes and cardiovascular disease. However, further studies are necessary to
      reveal more detailed aspects of the mechanism of action of pMSCs on glucose
      induced endothelial damage in vitro and in vivo.

PMID- 30241572
TI  - The molecular mechanisms of increased radiosensitivity of HPV-positive
      oropharyngeal squamous cell carcinoma (OPSCC): an extensive review.
AB  - Head and neck carcinomas (HNCs) collectively are the sixth most common cancer
      with an annual incidence of about 400,000 cases in the US. The most well
      established risk factors for HNCs are tobacco and alcohol abuse. With the
      increasing public awareness, the incidence of HNCs is decreasing. But there is an
      increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been
      observed during the last decade. This phenomena is associated with persistent
      infection with high-risk HPV. HPV associated OPSCC patients tend to be younger
      males of high socioeconomic status. The increasing incidence causes a significant
      loss to social resources, given that it's reported that HPV associated OPSCC
      represents about 60% of OPSCC cases. There is a growing amount of data supporting
      the hypothesis that HPV-associated OPSCC has a better survival rate due to a
      higher sensitivity to chemotherapy and radiotherapy as compared to HPV-unrelated
      OPSCC. Although the HPV positivity is associated with increased radio
      sensitivity, the underlying mechanisms are not yet fully understood. This review
      summarizes the current knowledge on the effects of HPV infection and its
      carcinogenesis on the radiosensitivity of OPSCC, from the molecular to histologic
      level, providing a comprehensive insight of this special tumor entity.

PMID- 30241573
TI  - Intraurethral co-transplantation of bone marrow mesenchymal stem cells and muscle
      derived cells improves the urethral closure.
AB  - BACKGROUND: Cell therapy constitutes an attractive alternative to treat stress
      urinary incontinence. Although promising results have been demonstrated in this
      field, the procedure requires further optimization. The most commonly proposed
      cell types for intraurethral injections are muscle derived cells (MDCs) and
      mesenchymal stem/stromal cell (MSCs). The aim of this study was to evaluate the
      effects of MDC-MSC co-transplantation into the urethra. METHODS: Autologous
      transplantation of labeled MDCs, bone marrow MSCs or co-transplantation of MDC
      MSC were performed in aged multiparous female goats (n = 6 in each group). The
      mean number of cells injected per animal was 29.6 * 106(+/- 4.3 * 106). PBS
      injected animals constituted the control group (n = 5). Each animal underwent
      urethral pressure profile (UPP) measurements before and after the injection
      procedure. The maximal urethral closure pressure (MUCP) and functional area (FA)
      of UPPs were calculated. The urethras were collected at the 28th or the 84th day
      after transplantation. The marker fluorochrome (DID) was visualized and
      quantified using in vivo imaging system in whole explants. Myogenic
      differentiation of the graft was immunohistochemically evaluated. RESULTS: The
      grafted cells were identified in all urethras collected at day 28 regardless of
      injected cell type. At this time point the strongest DID-derived signal
      (normalized to the number of injected cells) was noted in the co-transplanted
      group. There was a distinct decline in signal intensity between day 28 and day 84
      in all types of transplantation. Both MSCs and MDCs contributed to striated
      muscle formation if transplanted directly to the external urethral sphincter. In
      the MSC group those events were rare. If cells were injected into the submucosal
      region they remained undifferentiated usually packed in clearly distinguishable
      depots. The mean increase in MUCP after transplantation in comparison to the pre
      transplantation state in the MDC, MSC and MDC-MSC groups was 12.3% (+/- 11.2%,
      not significant (ns)), 8.2% (+/- 9.6%, ns) and 24.1% (+/- 3.1%, p = 0.02),
      respectively. The mean increase in FA after transplantation in the MDC, MSC and
      MDC-MSC groups amounted to 17.8% (+/- 15.4%, ns), 15.2% (+/- 12.9%, ns) and 17.8%
      (+/- 2.5%, p = 0.04), respectively. CONCLUSIONS: The results suggest that MDC-MSC
      co-transplantation provides a greater chance of improvement in urethral closure
      than transplantation of each population alone.

PMID- 30241575
TI  - Eco-Friendly Pharmaceutical Analysis of Multicomponent Drugs Coformulated in
      Different Dosage Forms Using Multivariate Curve Resolution and Partial Least
      Squares: A Comparative Study.
AB  - Background: Considering the environmental impact of analytical procedures
      necessitates replacing the polluting analytical methods with green alternatives.
      Objective: This study aims to develop and validate a multivariate curve
      resolution-alternating least-squares (MCR-ALS) method with correlation constraint
      for the simultaneous determination of theophylline, ambroxol, and guaifenesin as
      target analytes in the presence of methylparaben and propylparaben as interfering
      components. In addition, a partial least-squares regression (PLSR) method was
      also developed and optimized. Method: The developed methods were validated
      according to International Conference on Harmonization guidelines and
      successfully applied for the quantification of the target analytes in different
      pharmaceutical dosage forms. Results: Figures of merit such as root mean square
      error of prediction, bias, standard error of prediction, and relative error of
      prediction for both models were calculated, and they showed similar and
      satisfactory results. Correlation coefficients ranged between 0.9988 and 0.9992,
      reflecting high predictive ability. The optimized methods were compared with a
      reported HPLC method using one-way analysis of variance and showed no significant
      difference regarding accuracy and precision. Conclusions: The proposed
      chemometrics methods can be used as an eco-friendly alternative for
      chromatographic techniques for the quality control analysis of the studied
      mixture in different pharmaceutical dosage forms. Highlights: An MCR-ALS model
      was developed. The developed model was compared with a PLSR model. Both models
      were validated and successfully used for the determination of a multicomponent
      pharmaceutical mixture. The developed method is eco-friendly, fast, reliable, and
      cost-effective.

PMID- 30241599
TI  - Bypassing Kinase Signaling in Mammalian Cells.
AB  - Serine phosphorylation is frequently used to control the activity of proteins.
      Eukaryotic cells employ cascades of these phosphorylation events to encode and
      distribute information. In this issue of Cell Chemical Biology, Beranek et al.
      (2018) report the creation of a system to genetically incorporate phosphoserine
      in mammalian cells, thereby circumventing upstream kinase signaling.

PMID- 30241600
TI  - A MALDI-TOF Approach to Ubiquitin Ligase Activity.
AB  - In this issue of Cell Chemical Biology,De Cesare et al. (2018) report the
      development of a high-throughput assay that measures E2/E3 enzyme activity by
      MALDI-TOF mass spectrometry and apply this to screen for small molecule E3
      inhibitors. This assay potentially accelerates the drug discovery for the
      ubiquitin ligation pathway.

PMID- 30241574
TI  - Paediatric Autism Communication Therapy-Generalised (PACT-G) against treatment as
      usual for reducing symptom severity in young children with autism spectrum
      disorder: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Prior evidence shows that behaviours closely related to the
      intervention delivered for autism are amenable to change, but it is more
      difficult to generalise treatment effects beyond the intervention context. We
      test an early autism intervention designed to promote generalisation of therapy
      acquired skills into home and school contexts to improve adaptive function and
      reduce symptoms. A detailed mechanism study will address the process of such
      generalisation. Objective 1 will be to test if the PACT-G intervention improves
      autism symptom outcome in the home and school context of the intervention as well
      as in the primary outcome research setting. Objective 2 will use the mechanism
      analysis to test for evidence of acquired skills from intervention generalizing
      across contexts and producing additive effects on primary outcome.
      METHODS/DESIGN: This is a three-site, two-parallel-group, randomised controlled
      trial of the experimental treatment plus treatment as usual (TAU) versus TAU
      alone. Children aged 2-11 years (n = 244 (122 intervention/122 TAU; ~ 82/site)
      meeting criteria for core autism will be eligible. The experimental intervention
      builds on a clinic-based Pre-school Autism Communication Treatment model (PACT),
      delivered with the primary caregiver, combined with additional theory- and
      evidence-based strategies designed to enhance the generalisation of effects into
      naturalistic home and education contexts. The control intervention will be TAU.
      PRIMARY OUTCOME: autism symptom outcome, researcher-assessed using a standardised
      protocol. SECONDARY OUTCOMES: autism symptoms, child interaction with parent or
      teacher, language and reported functional outcomes in home and school settings.
      Outcomes measured at baseline and 12-month endpoint in all settings with interim
      interaction measurements (7 months) to test treatment effect mechanisms. Primary
      analysis will estimate between-group difference in primary outcome using analysis
      of covariance with test of homogeneity of effect across age group. Mechanism
      analysis will use regression models to test for mediation on primary outcome by
      parent-child and teaching staff-child social interaction. DISCUSSION: This is an
      efficacy and mechanism trial of generalising evidence-based autism treatment into
      home and school settings. It will provide data on whether extending treatment
      across naturalistic contexts enhances overall effect and data on the mechanism in
      autism development of the generalisation of acquired developmental skills across
      contexts. TRIAL REGISTRATION: ISRCTN, ID: 25378536 . Prospectively registered on
      9 March 2016.

PMID- 30241601
TI  - Targeting Nucleoporin POM121-Importin beta Axis in Prostate Cancer.
AB  - Nuclear pores are nanomachines acting as gatekeepers of molecular transport
      across nuclear membranes. In a recent issue of Cell, Rodriguez-Bravo et al.
      (2018) demonstrates that nuclear pores promote aggressive prostate cancer by
      snowballing POM121-importin beta-driven nuclear import. Treatment with
      Importazole, an importin beta inhibitor, impeded tumor aggressiveness, presenting
      a potential therapeutic strategy.

PMID- 30241602
TI  - PI 3-Kinase Signaling: AKTing up inside the Cell.
AB  - In this issue of Molecular Cell, Liu et al. (2018) show that PI34P2 and PIP3, the
      lipid products of class I phosphoinositide 3-kinase (PI3K), display distinct
      spatiotemporal kinetics in cells that result in differential activation of the
      effectors AKT1, AKT2, and AKT3.

PMID- 30241603
TI  - Mechanism for Synthetic Lethality in BRCA-Deficient Cancers: No Longer Lagging
      Behind.
AB  - Two recent studies implicate PARP as sensors of incompletely processed Okazaki
      fragments, changing our view about how single-strand breaks arise in unperturbed
      cells. Unligated Okazaki fragments may trigger homologous recombination-mediated
      repair and underpin genome instability in BRCA1/BRCA2-deficient cancers.

PMID- 30241604
TI  - A Scientist's Oath.
AB  - Data on the perceptions of scientists suggest a moderate public distrust of
      scientist's motivations. Bettridge et al. suggest scientist's reluctance to
      engage the public on controversial ethical issues may be a contributing factor.
      The authors propose a Scientist's Oath to send a clear message to the public
      about our ideals.

PMID- 30241605
TI  - DNA Methylation Clocks in Aging: Categories, Causes, and Consequences.
AB  - Age-associated changes to the mammalian DNA methylome are well documented and
      thought to promote diseases of aging, such as cancer. Recent studies have
      identified collections of individual methylation sites whose aggregate
      methylation status measures chronological age, referred to as the DNA methylation
      clock. DNA methylation may also have value as a biomarker of healthy versus
      unhealthy aging and disease risk; in other words, a biological clock. Here we
      consider the relationship between the chronological and biological clocks, their
      underlying mechanisms, potential consequences, and their utility as biomarkers
      and as targets for intervention to promote healthy aging and longevity.

PMID- 30241606
TI  - Multi-level Proteomics Identifies CT45 as a Chemosensitivity Mediator and
      Immunotherapy Target in Ovarian Cancer.
AB  - Most high-grade serous ovarian cancer (HGSOC) patients develop resistance to
      platinum-based chemotherapy and recur, but 15% remain disease free over a decade.
      To discover drivers of long-term survival, we quantitatively analyzed the
      proteomes of platinum-resistant and -sensitive HGSOC patients from minute amounts
      of formalin-fixed, paraffin-embedded tumors. This revealed cancer/testis antigen
      45 (CT45) as an independent prognostic factor associated with a doubling of
      disease-free survival in advanced-stage HGSOC. Phospho- and interaction
      proteomics tied CT45 to DNA damage pathways through direct interaction with the
      PP4 phosphatase complex. In vitro, CT45 regulated PP4 activity, and its high
      expression led to increased DNA damage and platinum sensitivity. CT45-derived HLA
      class I peptides, identified by immunopeptidomics, activate patient-derived
      cytotoxic T cells and promote tumor cell killing. This study highlights the power
      of clinical cancer proteomics to identify targets for chemo- and immunotherapy
      and illuminate their biological roles.

PMID- 30241608
TI  - Dynamic Human Environmental Exposome Revealed by Longitudinal Personal
      Monitoring.
AB  - Human health is dependent upon environmental exposures, yet the diversity and
      variation in exposures are poorly understood. We developed a sensitive method to
      monitor personal airborne biological and chemical exposures and followed the
      personal exposomes of 15 individuals for up to 890 days and over 66 distinct
      geographical locations. We found that individuals are potentially exposed to
      thousands of pan-domain species and chemical compounds, including insecticides
      and carcinogens. Personal biological and chemical exposomes are highly dynamic
      and vary spatiotemporally, even for individuals located in the same general
      geographical region. Integrated analysis of biological and chemical exposomes
      revealed strong location-dependent relationships. Finally, construction of an
      exposome interaction network demonstrated the presence of distinct yet
      interconnected human- and environment-centric clouds, comprised of interacting
      ecosystems such as human, flora, pets, and arthropods. Overall, we demonstrate
      that human exposomes are diverse, dynamic, spatiotemporally-driven interaction
      networks with the potential to impact human health.

PMID- 30241607
TI  - Structural Basis for the RNA-Guided Ribonuclease Activity of CRISPR-Cas13d.
AB  - CRISPR-Cas endonucleases directed against foreign nucleic acids mediate
      prokaryotic adaptive immunity and have been tailored for broad genetic
      engineering applications. Type VI-D CRISPR systems contain the smallest known
      family of single effector Cas enzymes, and their signature Cas13d ribonuclease
      employs guide RNAs to cleave matching target RNAs. To understand the molecular
      basis for Cas13d function and explain its compact molecular architecture, we
      resolved cryoelectron microscopy structures of Cas13d-guide RNA binary complex
      and Cas13d-guide-target RNA ternary complex to 3.4 and 3.3 A resolution,
      respectively. Furthermore, a 6.5 A reconstruction of apo Cas13d combined with
      hydrogen-deuterium exchange revealed conformational dynamics that have
      implications for RNA scanning. These structures, together with biochemical and
      cellular characterization, provide insights into its RNA-guided, RNA-targeting
      mechanism and delineate a blueprint for the rational design of improved
      transcriptome engineering technologies.

PMID- 30241609
TI  - The Energetics and Physiological Impact of Cohesin Extrusion.

PMID- 30241610
TI  - Structural Basis of Smoothened Activation in Hedgehog Signaling.

PMID- 30241611
TI  - A Thalamic Circuit Lights up Mood.
AB  - The contributions of areas downstream of retinal ganglion cells involved in the
      processing and regulation of mood remain largely unspecified. In this issue of
      Cell, Fernandez et al. (2018) identify a thalamic circuit within the
      perihabenular region (pHb) linking daily changes of light pattern to mood
      regulation.

PMID- 30241612
TI  - Sugar Turns Bacteria Sweet: A Peace Offering in the Gut.
AB  - Following an infection, a subset of individuals can remain disease free despite
      harboring a pathogen for a prolonged period. In this issue of Cell, Sanchez et
      al. demonstrate that a metabolically favorable host response can drive an
      otherwise lethal bacterial pathogen to abandon virulence and become a commensal
      microorganism.

PMID- 30241613
TI  - Chromatin Domains Go on Repeat in Disease.
AB  - TAD boundaries are insulators of genomic neighborhoods. In this issue, Sun et al.
      show that disease-associated tandem repeats are located to TAD boundaries and
      affect their insulation. The findings have important implications for TAD
      function and mechanisms underlying diseases such as fragile X syndrome and
      Huntington's disease.

PMID- 30241614
TI  - Human Diseases from Gain-of-Function Mutations in Disordered Protein Regions.
AB  - Although there is much focus on the impact of mutations on structured protein
      domains, less is known about their impact on unstructured regions. In this issue,
      Meyer et al. demonstrate that mutations resulting in the emergence of new short
      linear peptide motifs within intrinsically disordered protein regions can cause
      human genetic diseases by gain of function.

PMID- 30241616
TI  - Impact of U.S. Antismoking TV Ads on Spanish-Language Quitline Calls.
AB  - INTRODUCTION: Cigarette smoking is a major preventable cause of disease and death
      among U.S. Hispanics. Tobacco-cessation quitlines have been shown to increase
      quitting among Hispanics. However, the use of quitlines by this population
      remains low, especially among Spanish-speaking Hispanics. This study evaluates
      the promotion of 1-855-DEJELO-YA (a quitline portal that routes callers to state
      specific Spanish-language services) implemented as part of the Centers for
      Disease Control and Prevention's national Tips From Former Smokers(r) (Tips(r))
      campaign. Additionally, this study examines how media content impacted calls to 1
      855-DEJELO-YA. METHODS: Using National Cancer Institute data on calls to 1-855
      DEJELO-YA from February 2013 to December 2014, multivariate linear regressions
      were conducted of weekly area code-level call volume as a function of media
      market-level Gross Rating Points for Tips Spanish-language TV ads tagged with 1
      855-DEJELO-YA. The models were adjusted for covariates, including market-level
      population characteristics and state fixed effects. The data were analyzed from
      October 2017 through April 2018. RESULTS: Greater exposure to Tips Spanish
      language ads was associated with increased calls to 1-855-DEJELO-YA (p<0.001). On
      average, each additional 100 Tips Gross Rating Points per media market increased
      calls by 0.56 (95% CI=0.45, 0.67) calls/week/area code, representing ? 974
      additional calls beyond the baseline. Media messages highlighting health
      consequences of smoking had a greater effect size than messages highlighting
      health effects of secondhand smoke. CONCLUSIONS: A national Spanish-language
      quitline number could be a useful cessation resource for Spanish-speaking
      cigarette smokers. Opportunities exist to increase use of this number through a
      national Spanish-language media campaign, particularly by focusing campaign
      messages on the health consequences of smoking.

PMID- 30241617
TI  - Lifestyle Indices and Cardiovascular Disease Risk: A Meta-analysis.
AB  - CONTEXT: Several studies investigated lifestyle indices to account for
      interrelations between lifestyle behaviors and cardiovascular disease risk. So
      far, no systematic review has been conducted. Thus, the aim is to summarize the
      evidence of associations between lifestyle indices and cardiovascular disease
      risk in observational prospective studies. EVIDENCE ACQUISITION: A systematic
      literature search was conducted in two databases in February 2018. Multivariable
      adjusted risk estimates were combined using random effects models comparing the
      highest with the lowest healthy lifestyle score. Additionally, meta-analyses for
      cardiovascular disease types, such as stroke and heart failure, were conducted.
      Heterogeneity was assessed using I2 index. EVIDENCE SYNTHESIS: The search
      identified 27 studies, of which 22 were included in the meta-analyses. Most
      lifestyle indices included physical activity, smoking, diet, alcohol consumption,
      and body weight. A healthy lifestyle was associated with a reduced risk of 66%
      for cardiovascular disease (95% CI=0.28, 0.41, I2=79.1%), 60% for stroke, and 69%
      for heart failure. A dose-response effect for adherence to an increasing number
      of healthy behaviors and cardiovascular disease risk was observed. Statistical
      heterogeneity was found, suggesting that the definition of the lifestyle indices
      and components varied substantially between the studies. CONCLUSIONS: Adherence
      to several healthy lifestyle behaviors simultaneously was associated with a 66%
      reduced cardiovascular disease risk compared with adopting none or only one
      behavior. Despite heterogeneity of indices, consistent inverse associations
      across studies underscore the relevance of adopting healthy behaviors at all.
      More research on other lifestyle behaviors, such as sleep duration or sedentary
      behavior in combination, is warranted.

PMID- 30241618
TI  - Vehicle Danger and Older Pedestrian Safety.

PMID- 30241615
TI  - Identification of the Human Skeletal Stem Cell.
AB  - Stem cell regulation and hierarchical organization of human skeletal progenitors
      remain largely unexplored. Here, we report the isolation of a self-renewing and
      multipotent human skeletal stem cell (hSSC) that generates progenitors of bone,
      cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are
      present in fetal and adult bones and can also be derived from BMP2-treated human
      adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene
      expression analysis of individual hSSCs reveals overall similarity between hSSCs
      obtained from different sources and partially explains skewed differentiation
      toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion
      in response to acute skeletal injury. In addition, hSSC-derived stroma can
      maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions.
      Finally, we combine gene expression and epigenetic data of mouse skeletal stem
      cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent
      pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT.

PMID- 30241619
TI  - Intimate Partner Violence and Its Multiple Negative Consequences.

PMID- 30241620
TI  - Letter to the Editor Regarding U.S. Preventive Services Task Force Priorities for
      Prevention Research.

PMID- 30241621
TI  - Diet and Activity Assessments and Interventions Using Technology in Older Adults.
AB  - : This paper reports on the findings and recommendations specific to older adults
      from the "Tech Summit: Innovative Tools for Assessing Diet and Physical Activity
      for Health Promotion" forum organized by the North American branch of the
      International Life Sciences Institute. The summit aimed to investigate current
      and emerging challenges related to improving energy balance behavior assessment
      and intervention via technology. The current manuscript focuses on how novel
      technologies are applied in older adult populations and enumerated the barriers
      and facilitators to using technology within this population. Given the multiple
      applications for technology in this population, including the ability to monitor
      health events and behaviors in real time, technology presents an innovative
      method to aid with the changes associated with aging. Although older adults are
      often perceived as lacking interest in and ability to adopt technologies, recent
      studies show they are comfortable adopting technology and user uptake is high
      with proper training and guided facilitation. Finally, the conclusions suggest
      recommendations for future research, including the need for larger trials with
      clinical outcomes and more research using end-user design that includes older
      adults as technology partners who are part of the design process. THEME
      INFORMATION: This article is part of a theme issue entitled Innovative Tools for
      Assessing Diet and Physical Activity for Health Promotion, which is sponsored by
      the North American branch of the International Life Sciences Institute.

PMID- 30241622
TI  - Dietary Intake and Physical Activity Assessment: Current Tools, Techniques, and
      Technologies for Use in Adult Populations.
AB  - : Accurate assessment of dietary intake and physical activity is a vital
      component for quality research in public health, nutrition, and exercise science.
      However, accurate and consistent methodology for the assessment of these
      components remains a major challenge. Classic methods use self-report to capture
      dietary intake and physical activity in healthy adult populations. However, these
      tools, such as questionnaires or food and activity records and recalls, have been
      shown to underestimate energy intake and expenditure as compared with direct
      measures like doubly labeled water. This paper summarizes recent technological
      advancements, such as remote sensing devices, digital photography, and
      multisensor devices, which have the potential to improve the assessment of
      dietary intake and physical activity in free-living adults. This review will
      provide researchers with emerging evidence in support of these technologies, as
      well as a quick reference for selecting the "right-sized" assessment method based
      on study design, target population, outcome variables of interest, and economic
      and time considerations. THEME INFORMATION: This article is part of a theme issue
      entitled Innovative Tools for Assessing Diet and Physical Activity for Health
      Promotion, which is sponsored by the North American branch of the International
      Life Sciences Institute.

PMID- 30241623
TI  - Urticaria: A comprehensive review: Epidemiology, diagnosis, and work-up.
AB  - Urticaria is a common clinical condition presenting with wheals (hives),
      angioedema, or both. Urticaria has a complex pathogenesis, along with a high
      disease burden, a significant impact on quality of life, and high health care
      costs. The first article in this continuing medical education series covers the
      definition, classification, epidemiology, diagnosis, and work-up of urticaria,
      taking into account the recent literature and the best available evidence.

PMID- 30241624
TI  - Urticaria: A comprehensive review: Treatment of chronic urticaria, special
      populations, and disease outcomes.
AB  - Second-generation antihistamines are considered first-line agents in the
      treatment of chronic urticaria because of their safety and efficacy profile. Some
      patients require higher doses of H1 antihistamines alone or in combination with
      other classes of medications, including H2 antihistamines, leukotriene receptor
      antagonists, or first-generation H1 antihistamines. One major therapeutic advance
      has been omalizumab, a humanized monoclonal anti-immunoglobulin E that was
      recently approved by the US Food and Drug Administration for the treatment of
      chronic urticaria that is unresponsive to H1 antagonists. In addition, the second
      article in this continuing medical education series outlines several evidence
      based alternative treatments for urticaria and the differences in recommendations
      between 2 major consensus groups (the European Academy of Allergy and Clinical
      Immunology/World Allergy Organization and the American Academy of Allergy, Asthma
      and Immunology/American College of Allergy, Asthma and Immunology Joint Task
      Force).

PMID- 30241625
TI  - Clinically amelanotic or hypomelanotic melanoma: Anatomic distribution, risk
      factors, and survival.
AB  - BACKGROUND: The recognition and diagnosis of clinically amelanotic or
      hypomelanotic melanoma is a challenge. OBJECTIVE: This study aimed to examine the
      anatomic distribution and risk factors associated with clinically amelanotic or
      hypomelanotic melanoma and compare the survival of patients with clinically
      amelanotic or hypomelanotic melanoma with that of patients with pigmented
      melanoma. METHODS: A prospective cohort study of all cases of primary invasive
      melanoma managed at a tertiary referral center was performed. RESULTS: There were
      a total of 3913 invasive melanomas, and 384 (9.8%) were clinically amelanotic or
      hypomelanotic. Skin phototype I; red as well as blonde hair color; actinic
      keratoses; nodular, desmoplastic, and lentigo maligna subtype; increased Breslow
      thickness; and mitoses were independently associated with amelanotic or
      hypomelanotic melanoma (P < .05). After adjustment for subtype and thickness, the
      face, ears, lateral aspect of the neck, upper portion of the arm, posterior
      aspect of the forearm, dorsal aspect of the hand, and anterior aspect of the
      lower portion of the leg were associated with increased odds of amelanotic or
      hypomelanotic melanoma when compared with the upper portion of the back (P <
      .05). Mortality risk from melanoma appeared greater for amelanotic or
      hypomelanotic melanoma than for pigmented melanoma (hazard ratio, 1.5; 95%
      confidence interval, 1.1-2.1) but was similar once Breslow thickness was taken
      into account. LIMITATIONS: Single tertiary referral center. CONCLUSION: Although
      clinically amelanotic or hypomelanotic melanoma can occur on all body sites, it
      is more common on chronically sun-exposed areas. Clinicians should have an
      increased index of suspicion in patients with a sun-sensitive skin phenotype, red
      hair, and associated actinic keratoses.

PMID- 30241626
TI  - The case of the dog and the blue light.

PMID- 30241627
TI  - ?

PMID- 30241628
TI  - ?

PMID- 30241629
TI  - [Burnout syndrome: definition, typology and management].
AB  - Although burnout syndrome was first described clinically about sixty years ago,
      it hasn't yet found its place in the classification of mental disorders. The wide
      range of clinical signs and aetiopathogenic theories has certainly contributed to
      this situation. There are different clinical forms of burnout and various
      therapeutic strategies. Psychiatrists play a key role in the multidisciplinary
      diagnosis of burnout.

PMID- 30241630
TI  - [Understanding the complex, multifaceted and multifactorial psychosocial risks].
AB  - Fatigue, anxiety, harassment, burnout, stress, etc., the psychosocial risk
      category brings together multidimensional (physiological, psychological,
      social...) heterogeneous and complex problems and pathological entities. These
      aspects are also associated with significant ideological and socio-economic
      issues (employer liability, cost to the community ...). Thus, how can we make
      sense of this increase in complaints? Is work harder now than it used to be?

PMID- 30241631
TI  - [Burnout: priorities of effective treatment].
AB  - Nowadays, burnout, i.e. professional exhaustion due to chronic stress, can be
      treated effectively and without sequelae. However, certain key points must be
      observed in the management of burnout: medical support other than treatment for
      depression, active involvement in the treatment process during sick leave,
      personal reassessment and return to work at the right time, with appropriate
      preparation.

PMID- 30241632
TI  - [A consultation on the topic of "anxiety in the workplace" as a basis for
      prevention].
AB  - On the initiative of health insurance companies, a group of occupational health
      professionals has been formed in the Rhone-Alpes region. This has resulted in the
      creation of a facility dedicated to the management and prevention of anxiety in
      the workplace. Run by a multidisciplinary team, the facility welcomes
      professionals who are dealing with toxic situations in the workplace. The goal is
      to help sufferers make the link between their health and their professional
      experience. Illustration of a constructive and original commitment.

PMID- 30241634
TI  - ?

PMID- 30241633
TI  - [When burnout sweeps into CMPs].
AB  - There have been significant changes in recent years in what psychiatrists are
      expected to accomplish in CMP [centre medicopsychologique (medical-psychological
      centre)] consultations. Back in the 1980s, most of the patients seen were
      psychotic. Then, all of a sudden, psychiatrists began to see a whole new category
      of cases at CMPs: patients who were exhausted and no longer able to do their jobs
      properly. This included a wave of civil servants affected by restructuring,
      followed by private sector employees. These days, most of those who consult for
      burnout are health workers.

PMID- 30241635
TI  - ?

PMID- 30241636
TI  - Uncomplicated Acute Pancreatitis: Evidenced-Based Management Decisions.
AB  - Acute pancreatitis is among the most common gastrointestinal disorders requiring
      hospitalization worldwide. Establishing the cause of acute pancreatitis ensures
      appropriate management and proper health care resource utilization. Causes of
      acute pancreatitis include biliary, alcohol use, hypertriglyceridemia,
      hypercalcemia, drug-induced, autoimmune, hereditary/genetic, and anatomic
      abnormalities. Fluid therapy remains the cornerstone of managing acute
      pancreatitis. This article provides a brief summary of current evidence-based
      practices in the diagnosis and management of uncomplicated acute pancreatitis.

PMID- 30241637
TI  - How to Avoid Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.
AB  - Pancreatitis remains the most common and potentially devastating complication of
      endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Recent
      advances in prophylaxis have improved but not eliminated this problem,
      underscoring the importance of ongoing research toward this goal. This review
      aims to provide an evidence-based approach to post-ERCP pancreatitis prevention
      through patient selection, risk stratification, procedural technique, and
      multimodality prophylaxis, and discusses ongoing and future research initiatives
      in this important area.

PMID- 30241638
TI  - The Role of Endotherapy in Recurrent Acute Pancreatitis.
AB  - Patients with recurrent acute pancreatitis (RAP) have few treatment options
      available to them to manage their symptoms or prevent progression to chronic
      pancreatitis. At present, endotherapy is typically pursued as a means to achieve
      symptom remission and reduce rates of recurrence, hospitalization, abdominal
      pain, narcotic use, and surgical intervention. However, evidence that endotherapy
      effectively alters the natural history of disease remains limited. This article
      reviews the recent literature on the efficacy of endoscopic intervention in the
      treatment RAP with a focus on high-quality prospective randomized controlled
      studies. Additional studies are needed to corroborate these findings.

PMID- 30241639
TI  - Systematic Review of Endoscopic Cyst Gastrostomy.
AB  - Since the original description of pancreatic fluid collections (PFC) in 1761 by
      Morgagni, their diagnosis, description, and management have continued to evolve.
      The mainstay of therapy for symptomatic PFCs has been the creation of a
      communication between a PFC and the stomach, to enable drainage. Surgical
      creation of these drainage conduits had been the gold standard of therapy;
      however, there has been a paradigm shift in recent years with an increasing role
      of endoscopic drainage. The techniques of endoscopic drainage have evolved from
      blind fluid aspiration to include endoscopic necrosectomy and the placement of
      lumen-apposing metal stents.

PMID- 30241640
TI  - Management of Autoimmune Pancreatitis.
AB  - Type 1 autoimmune pancreatitis (AIP) is an IgG-4-related systemic disease that
      can manifest as a pancreatic disorder or another disorder of presumed autoimmune
      origin. Type 2 disease is typically characterized by absent IgG-4-positive cells.
      As patients often present with acute pancreatitis, obstructive jaundice, or
      pancreatic mass, it is imperative to exclude malignancy, a more common diagnosis.
      AIP may respond to corticosteroids, and has a strong association with other
      immune-mediated diseases. Recent literature suggests the benefit of immune
      modulating therapy, including rituximab, although no consensus exists. This
      review covers the essentials of diagnosis, but focuses primarily on management of
      AIP.

PMID- 30241641
TI  - Pancreatic Insufficiency: What Is the Gold Standard?
AB  - Endoscopic pancreatic function testing assesses exocrine insufficiency and
      chronic pancreatitis. Indirect pancreatic function tests have limited sensitivity
      and specificity in early disease stages. Magnetic resonance
      cholangiopancreatography shows promise in detecting early changes as a direct
      measure of pancreatic function. This article summarizes the evolution of
      pancreatic function testing and highlights areas for future research, such as
      development of diagnostic biomarkers to stratify disease severity and targeted
      therapies to retard disease progression.

PMID- 30241642
TI  - Current Guideline Controversies in the Management of Pancreatic Cystic Neoplasms.
AB  - Pancreatic cystic lesions are a common clinical entity. The majority are
      neoplastic and have the potential for malignant transformation. To assist with
      patient management, a number of clinical guidelines have been developed over the
      past decade. However, controversies exist in regards to the various guidelines
      and treatment strategies they offer. This article will review the various
      clinical guidelines for management of pancreatic cysts, describe the limitations
      of these guidelines, and present future directions for improvement in clinical
      decision making for patients diagnosed with a pancreatic cystic neoplasm.

PMID- 30241643
TI  - The Use of Biomarkers in the Risk Stratification of Cystic Neoplasms.
AB  - Cyst fluid biomarkers may be used to identify pancreatic cyst subtypes.
      Biomarkers are selected based on their ability to accurately distinguish mucinous
      from nonmucinous cysts and to risk stratify cysts based on malignant potential.
      Biomarkers of interest include but are not limited to amylase, oncogenes, DNA
      analysis, and epigenetic markers. The introduction of next-generation sequencing
      and molecular panels has aided in improved diagnostic accuracy and risk
      stratification. This review presents the diagnostic performance of currently
      available biomarkers and proposes an algorithm to incorporate their use in the
      diagnosis of pancreatic cysts.

PMID- 30241645
TI  - Celiac Plexus Block and Neurolysis: A Review.
AB  - Pain is often associated with chronic pancreatitis and pancreatic cancer. Often
      times opioids are used to treat pain; however, the use of opioids is frequently
      difficult. Endoscopic ultrasound-guided celiac plexus block and celiac plexus
      nuerolysis are safe and effective modalities used to alleviate pain. Celiac
      plexus block is a transient interruption of the plexus by local anesthetic, while
      celiac plexus neurolysis is prolonged interruption of the transmission of pain
      from the celiac plexus using chemical ablation. Celiac plexus block is generally
      performed in the unilateral position, while celiac plexus neurolysis is performed
      in the unilateral or bilateral position.

PMID- 30241644
TI  - Interventional Endoscopic Ultrasonography in the Pancreas.
AB  - Endoscopic ultrasonography (EUS) has enabled therapeutic endoscopists to
      intervene on conditions that have otherwise not been accessible with conventional
      endoscopy. Inflammatory fluid collections of the pancreas that may benefit from
      drainage are often not identifiable without EUS. Furthermore, EUS may improve the
      safety of transmural drainage by allowing for the identification of intervening
      blood vessels and reducing the need for fluoroscopy, and is complemented by new
      devices that simplify the access and stent delivery process. The use of EUS has
      also made the treatment of various pancreatic duct disorders possible when direct
      access is otherwise impossible.

PMID- 30241646
TI  - The Role of Genetics in Pancreatitis.
AB  - Individuals with acute recurrent and chronic pancreatitis may have an inherited
      predisposition to the development of the disease. Pancreatitis in the setting of
      a significant family history of the disease can be classified as hereditary or
      familial pancreatitis. In this article, the authors closely examine the specific
      genes implicated in pancreatitis, investigate the role of genetic testing for
      diagnosis, and describe the impact of genetic testing results on clinical
      management.

PMID- 30241647
TI  - Total Pancreatectomy with Autologous Islet Cell Transplantation.
AB  - First described in the early 1980s, total pancreatectomy with autologous islet
      cell transplantation for the treatment of chronic pancreatitis is still only
      offered in select centers worldwide. Indications, process details including
      surgery as well as islet isolation, and results are reviewed. In addition, areas
      for further research to optimize results are identified.

PMID- 30241648
TI  - Management of Benign Pancreatic Diseases.

PMID- 30241649
TI  - Preface.

PMID- 30241650
TI  - The guise of innocent slumber.

PMID- 30241651
TI  - Addressing the need for validation of a touchscreen psychomotor vigilance task:
      important considerations for sleep health research.

PMID- 30241652
TI  - Objective sleep in pregnant women: a comparison of actigraphy and
      polysomnography.
AB  - OBJECTIVES: To compare different actigraphy scoring settings with polysomnography
      (PSG) for 1 night of total sleep time (TST), sleep efficiency (SE), wake after
      sleep onset (WASO), and sleep onset latency (SOL) in healthy pregnant women
      between 6 and 7 months of gestation. DESIGN: Secondary analysis using data from a
      case-control study. SETTING: A large university-affiliated hospital in the
      Midwestern United States. PARTICIPANTS: A total of 78 pregnant women were
      recruited, among which 38 healthy women with uncomplicated pregnancies were
      included for this analysis. MEASUREMENTS: Participants had an overnight PSG
      assessment at a sleep center while simultaneously wearing an actigraph
      (Minimitter; Philips Respironics, Andover, MA). Sleep parameters from both
      devices included TST, SE, WASO, and SOL. Four scoring settings were used to
      obtain these parameters from actigraphy. Bland-Altman tests were used to evaluate
      the agreement between sleep variables scored independently from actigraphy and
      PSG. RESULTS: The default scoring setting (10-by-40) yielded significantly
      different results from the PSG (P < .01). The 10 immobile/mobile minutes for
      sleep onset/end with an activity threshold of 10 (10-by-10) produced estimations
      of TST, SE, and WASO closest to those produced by PSG. When this setting was
      used, the mean differences between PSG- and actigraphy-assessed TST, SE, and WASO
      were -1.9 minutes, -0.4%, and 7.4 minutes. When the 10 and 15 immobile/mobile
      minutes for sleep onset/end were used, the difference between PSG- and actigraphy
      assessed SOL was approximately 4 to 5 minutes. CONCLUSIONS: Findings from this
      study do not support the use of default actigraph settings in pregnant women. In
      contrast, the 10-by-10 scoring setting provided the greatest agreement and least
      bias in comparison with PSG for sleep measurements. The 10-by-10 scoring setting
      is recommended to be used in studies consisting of pregnant women.

PMID- 30241653
TI  - Maternal antenatal stress has little impact on child sleep: results from a
      prebirth cohort in Mexico City.
AB  - STUDY OBJECTIVES: Maternal antenatal stress may influence offspring development
      and behavior, but any association with child sleep is unknown. METHODS: From 2007
      to 2011, we recruited pregnant women in Mexico City to the Programming Research
      in Obesity, Growth, Environment, and Social Stressors prebirth cohort. Mothers
      completed the Perceived Stress Scale (PSS, a 4-item questionnaire assessing past
      month stress) and the Crisis in Family Systems measure assessing negative life
      events (NLEs; how many domains among the 11 assessed in which the mother
      experienced a stressful event in the prior 6 months)-with higher scores
      reflecting higher stress-and provided 5 timed salivary samples per day on 2
      consecutive days, from which we derived cortisol area under the curve, slope, and
      awakening response. At age 4-6 years, children's sleep was estimated using
      accelerometry over a 7-day period. We performed secondary analysis of
      associations of antenatal maternal stress with child sleep duration and
      efficiency (time asleep/time in bed) using linear regression adjusted for
      maternal and child characteristics. RESULTS: Among 594 mother-child dyads, mean
      antenatal PSS score was 5.2 (SD = 3.2) out of 16, and mean NLE was 3.2 (SD = 2)
      out of 11; child sleep duration was 7.7 hours (SD = 0.7), and sleep efficiency
      was 79% (SD = 6). There was no association between any of the stress measures
      PSS, NLE, or salivary cortisol-and sleep duration or sleep efficiency in adjusted
      or unadjusted models. CONCLUSIONS: Among mother-child dyads in a Mexico City
      cohort, antenatal stress was not associated with important changes in child sleep
      at 4-6 years.

PMID- 30241654
TI  - Sleepiness as a pathway linking race and socioeconomic status with academic and
      cognitive outcomes in middle childhood.
AB  - OBJECTIVES: This study examined self-reported sleepiness as a pathway of effects
      underlying racial and socioeconomic disparities in children's academic and
      cognitive performance. DESIGN: The study design was longitudinal, and path
      modeling was used to test study hypotheses. SETTING: Data were collected from
      participants residing in semirural communities and small towns surrounding
      Auburn, AL. PARTICIPANTS: Children (N = 282; 52% boys) participated in the study
      when they were 9 (M = 9.44, SD = .71) and 11 (M = 11.33, SD = .69) years old. The
      sample was 65% White/European American and 35% Black/African American. The
      majority of the children (63%) were living at or below the poverty line.
      MEASUREMENTS: At age 9, children reported on their daytime sleepiness over the
      prior 2 weeks. At ages 9 and 11, children completed cognitive assessments in the
      laboratory, teachers reported on children's academic functioning, and schools
      provided state (Alabama) standardized test scores. RESULTS: African American
      children and children from lower socioeconomic status homes reported greater
      sleepiness. Greater sleepiness, in turn, predicted lower academic functioning,
      cognitive performance, and Alabama standardized test scores. Sleepiness was a
      significant intervening variable, but not a mediator, in these pathways. Race was
      a stronger predictor of sleepiness than socioeconomic status when both were
      entered in the same model. CONCLUSIONS: Results highlight sleepiness as a pathway
      of effects linking race and socioeconomic status to academic and cognitive
      outcomes. Psychoeducation targeting sleepiness for African American and lower
      socioeconomic status children may be beneficial for boosting achievement.

PMID- 30241656
TI  - Sleep and cardiometabolic health by government-assisted rental housing status
      among Black and White men and women in the United States.
AB  - OBJECTIVES: To investigate Black-White disparities in suboptimal sleep and
      cardiometabolic health by government-assisted rental housing status. DESIGN:
      National Health Interview Survey (NHIS) pooled cross-sectional data (2004-2016).
      SETTING: United States. PARTICIPANTS: Black and White adult participants (n =
      80,880). MEASUREMENTS: Poisson regression with robust variance was used to
      estimate prevalence ratios (PRs) and 95% confidence intervals for self-reported
      unrecommended (<6 hours), short (<=6-<7 hours), and long (>9 hours) sleep
      duration (each separately vs recommended (<=7-9 hours)) and sleep difficulties
      (eg, trouble falling/staying asleep >=3 days/week) (yes vs no) among Blacks
      compared to Whites within rental housing categories (government-assisted vs
      unassisted), separately, for men and women. Within sex/housing categories, we
      applied the same approach to compare cardiometabolic health outcomes (ie,
      overweight/obesity, hypertension, diabetes, heart disease, stroke) between Blacks
      with worse sleep and Whites with recommended sleep. Models were adjusted for age
      and other potential confounders. RESULTS: Participants' mean age was 42 +/- 18
      years, 57% were female, and 30% Black. Blacks in unassisted housing had a higher
      prevalence of unrecommended and short sleep (PR = 1.22 [1.15-1.30] -men, PR =
      1.14 [1.08-1.21] -women) compared to their White counterparts (phousing*race =
      0.001 -men, phousing*race = 0.008 -women), but no Black-White differences (PR =
      0.88 [0.73-1.07] -men, PR = 0.98 [0.89-1.09] -women) were observed among
      government-assisted renters. Generally, Blacks were less likely to report sleep
      difficulties than Whites. Cardiometabolic health disparities between Blacks with
      worse sleep and Whites with recommended sleep were generally smaller among
      government-assisted renters, but relationships varied by sex. CONCLUSIONS: There
      were no racial disparities in short sleep duration, and cardiometabolic health
      disparities were generally attenuated when Blacks and Whites resided in
      government-assisted rental housing.

PMID- 30241655
TI  - Exposure to neighborhood green space and sleep: evidence from the Survey of the
      Health of Wisconsin.
AB  - INTRODUCTION: Adequate sleep duration and quality are protective against many
      adverse health outcomes. Many individual-level predictors of poor sleep have been
      examined, but few studies have examined neighborhood-level influences. Despite
      known associations between neighborhood green space and sleep influencing factors
      (eg, physical activity, mental health), few studies have examined green space and
      sleep's relationship. Furthermore, little work has examined the relationship
      between the magnitude and type of neighborhood sounds and sleep. STUDY METHODS:
      We analyzed data from the Survey of the Health of Wisconsin database (n = 2712)
      for 2008-2013, a representative sample of Wisconsin residents ages 21-74.
      Outcomes included weekday and weekend sleep duration and self-rated sleep
      quality. Primary predictors were the proportion tree canopy (National Land Cover
      Database) and mean decibel levels of outdoor sound (US National Park Service) at
      the census block group level. Survey regression analysis was used to examine
      statistical associations, controlling for individual and neighborhood-level
      covariates. RESULTS: Models suggest a significant relationship (P < .05) between
      weekday sleep duration and green space, and between weekend/day sleep duration
      and human-made and total neighborhood sound. Increased percent tree canopy in a
      census block group was associated with lower odds of short weekday sleep (<6
      hours) (OR 0.76 [0.58-0.98]). Increased human-made and total mean decibel levels
      were associated with increased instances of short weekend and weekday sleep (OR
      1.05 [1.01-1.08] and 1.03 [1.01-1.06] respectively). CONCLUSIONS: Neighborhood
      tree canopy and sound levels may influence sleep duration and are potential
      targets for neighborhood-level interventions to improve sleep.

PMID- 30241657
TI  - Perceived school safety, perceived neighborhood safety, and insufficient sleep
      among adolescents.
AB  - OBJECTIVES: To examine whether perceptions of school safety and neighborhood
      safety are associated with insufficient sleep during adolescence. DESIGN: The
      Florida Youth Substance Abuse Survey (FYSAS) is a cross-sectional study of
      adolescents. SETTING: The state of Florida. PARTICIPANTS: Middle-school and high
      school students (n = 7,958) attending public schools in 2017. MEASUREMENTS: Based
      on National Sleep Foundation recommendations, sleep was categorized as
      insufficient (less than 7 hours) or sufficient (7 or more hours) using self
      reports of average sleep duration on school nights. Self-reports of perceived
      safety at school and perceived safety in one's neighborhood were modeled as
      predictors of insufficient sleep in logistic regression models when accounting
      for several covariates. RESULTS: Adjusting for model covariates, the odds of
      insufficient sleep among adolescents who feel unsafe both at school and in their
      neighborhood are 129% greater relative to adolescents who feel safe in both
      contexts. In comparison, the odds of insufficient sleep among adolescents who
      feel unsafe only at school are 39% greater relative to adolescents who feel safe
      both at school and in their neighborhood, and the odds of insufficient sleep
      among adolescents who feel unsafe only in their neighborhood are 71% greater
      relative to adolescents who feel safe both at school and in their neighborhood.
      CONCLUSIONS: The findings of this study indicate that efforts to improve the
      safety of salient social contexts in which adolescents develop may reduce the
      likelihood of insufficient sleep faced by a large portion of school-aged
      children.

PMID- 30241658
TI  - Stress levels are associated with poor sleep health among sexual minority men in
      Paris, France.
AB  - OBJECTIVE: The objective of this study was to examine the association between
      perceived stress and sleep health among a sample of sexual minority men (SMM).
      DESIGN: Cross-sectional survey. SETTING: Paris, France. PARTICIPANTS: Gay,
      bisexual and other SMM users >=18 years on a geosocial networking application in
      Paris, France (N = 580). MEASUREMENTS: Participants were directed to a web-based
      survey measuring stress, sleep health, and socio-demographics. Multivariate log
      binomial regression models were used to estimate the adjusted risk ratios (aRRs)
      and 95% confidence intervals (CIs) to examine how stress may affect different
      dimensions of sleep health: 1) poor sleep quality, 2) short sleep duration, 3)
      problems falling asleep, and 4) problems staying awake in the daytime. RESULTS:
      Most participants (69.9%) reported at least sometimes feeling stressed (compared
      to never or rarely). Additionally, results demonstrate that higher perceived
      stress was associated with poorer sleep health; compared with those who reported
      feeling stress never or rarely, those who felt stress sometimes, often, or always
      were more likely to experience poor sleep quality (aRR = 6.67; 95% CI = 3.61
      12.3), short sleep duration (aRR = 1.67; 95% CI = 1.17-2.38), problems falling
      asleep (aRR = 3.20; 95% CI = 2.26-4.52), and problems staying awake during the
      daytime (aRR = 3.52; 95% CI = 1.64-7.53). CONCLUSION: Elevated perceived stress
      can negatively influence sleep health among SMM in Paris, France.

PMID- 30241659
TI  - Sleep duration mediates the relationship between health behavior patterns and
      obesity.
AB  - OBJECTIVE: To examine associations between health behavior patterns and childhood
      obesity, and the mediating effect of sleep duration. DESIGN: Population-based
      survey. PARTICIPANTS: Secondary analysis of data from the Infant Feeding
      Practices Study (age 6 years, n = 1073). MEASUREMENTS: Mothers self-reported
      their child's health behaviors including physical activity (PA), screen time,
      sleep duration, and diet. Latent class analysis determined the child's patterns
      based on health behaviors. Sleep was examined as a mediator between the class
      membership variable and %BMIp95. RESULTS: A 3-class model fit the data best, with
      classes labeled as "Poorest eaters" (low fruit/vegetable consumption, high fast
      food), "Healthy" (low screen time, highest fruit/vegetable consumption) and
      "Active, super-eaters, highest screen time" (highest PA and screen time, ate the
      most). "Poorest eaters" had an increased %BMIp95 (beta = 4.11, P = .006) relative
      to the "Healthy" class. The "Poorest eaters" and "Active, super-eaters, highest
      screen time" classes had shorter sleep duration (beta = -0.51, P < .001; beta = 
      0.38, P < .001; respectively) relative to the "Healthy" class. Independent of
      class membership, each additional hour of sleep was associated with a %BMIp95
      that was 2.93 U lower (P < .001). CONCLUSIONS: Our results indicate that health
      behavior patterns mediated by sleep duration may influence a child's %BMIp95. The
      bi-directionality of the relationship between health behaviors and sleep remains
      unclear. Our findings suggest the importance of a constellation of health
      behaviors on childhood obesity. Interventions should include a multitude of
      health behaviors and consider the possibility that improving diet and activity
      behaviors may facilitate improved sleep and lowered obesity risk among children.

PMID- 30241660
TI  - Sleep duration and excess heart age among US adults.
AB  - OBJECTIVES: Insufficient sleep negatively impacts the cardiovascular system. No
      study has examined the association between sleep duration and heart age (person's
      predicted vascular age based on cardiovascular disease [CVD] risk profile). This
      study examines association between sleep duration and excess heart age (EHA;
      difference between heart age and chronological age) among US adults. DESIGN AND
      PARTICIPANTS: Cross-sectional 2007-2014 National Health and Nutrition Examination
      Survey data for respondents aged 30-74 years without CVD or stroke (n = 12,775).
      MEASUREMENTS: Self-reported sleep duration was classified into 5 categories (<=5,
      6, 7, 8, and >=9 hours). We used sex-specific Framingham heart age algorithm to
      calculate heart age and multivariable linear regression to examine association
      between sleep duration and EHA. RESULTS: A total of 13.4% (95% confidence
      interval 12.5-14.3), 24.2% (23.1-25.2), 31.0% (29.8-32.3), 25.9% (25.0-26.9), and
      5.5% (5.0-6.1) reported sleeping <=5, 6, 7, 8, and >=9 hours, respectively. We
      observed a nonlinear relationship between sleep duration and EHA using 7 hours as
      reference: EHA (adjusted for sociodemographics, body mass index, physical
      activity, Healthy Eating Index-2010, sleep disorder, and depression status) was
      5.1 (4.8-5.8), 4.5 (3.9-5.1), 3.7 (3.3-4.0), 4.5 (4.1-5.0), and 4.1 (3.3-4.9)
      years for sleep durations of <=5, 6, 7, 8 and >=9 hours, respectively (P = .015
      for quadratic trend). EHA was significantly higher among participants with lower
      education, lower income, and obesity. CONCLUSION: Mean adjusted EHA was lowest
      among adults who reported sleeping 7 hours per night and increased as adults
      reported sleeping fewer or more hours. Discussing sleep duration in the context
      of EHA may be helpful for patients and clinicians.

PMID- 30241661
TI  - Chronic sleep restriction affects the association between implicit bias and
      explicit social decision making.
AB  - OBJECTIVES: Previous work suggests that sleep restriction (SR) reduces cognitive
      control and may increase negative implicit biases. Here we investigated whether
      SR might influence decision making on a social-evaluative task where individuals
      had to make judgments of threat based on facial photographs. Furthermore, we
      investigated the effect of changes in negative implicit biases as a result of
      sleep restriction on this decision-making task. DESIGN: Fourteen healthy adults
      underwent two 3-week counterbalanced in-laboratory stays (chronic SR and control
      sleep [CS] conditions). Participants completed the Arab Muslim Names implicit
      association test (a measure of implicit bias/attitudes toward Arab Muslims) and
      the Karolinska Airport Task (a measure of explicit decision making). The
      Karolinska Airport Task requires participants to judge the potential
      dangerousness of individuals based on facial photographs. RESULTS: After SR,
      participants were more likely to deem individuals with less positive and more
      negative facial features as dangerous than after CS. In addition, after SR, those
      participants showing higher negative implicit bias toward Arab Muslims tended to
      consider as more dangerous individuals with more quintessentially untrustworthy
      facial features (r = 0.76, P = .007), whereas this relationship was
      nonsignificant after CS (r = 0.33, P = .28). CONCLUSIONS: These findings show not
      only that SR may increase implicit biases against a particular minority group but
      that SR also modifies how individuals make explicit decisions about another's
      trustworthiness based on facial features. These findings may have important
      implications for many occupations where workers who are routinely restricted of
      sleep are also responsible for making judgments about other people's
      trustworthiness (eg, police, security, military personnel).

PMID- 30241662
TI  - Calculating the contribution of sleep problems to undergraduates' academic
      success.
AB  - OBJECTIVES: The objective of this study is to determine to what degree sleep
      disturbances predict academic success, relative to other known risk factors for
      decreased academic performance. METHODS: We performed regression analyses on data
      from the Spring 2009 American College Health Association National College Health
      Assessment II dataset (n=55,322 students) to isolate the relative contribution of
      the frequency of sleep problems in the previous week to GPA and the likelihood of
      withdrawing from a course. In our estimations, we also controlled for other
      factors that influence academic success such as demographic and academic
      variables, drug and alcohol use, perceived stress, and employment hours. RESULTS:
      Sleep disturbances were found to be a significant independent predictor of
      academic problems; on average, each additional day per week that a student
      experienced sleep problems raised the probability of dropping a course by 10% and
      lowered the cumulative GPA by 0.02. Factors such as stress, binge drinking,
      marijuana and other illicit drug use, which typically receive more attention by
      university administrators, had similar or relatively smaller negative
      associations with academic success as compared to disturbed sleep. Approximately
      three quarters of students surveyed reported never receiving information about
      sleep from their university. CONCLUSIONS: Sleep education represents an
      underutilized opportunity for universities to maximize retention rates and
      academic success.

PMID- 30241663
TI  - Hours of service regulations for professional drivers in continental Latin
      America.
AB  - OBJECTIVES: To describe the hours of service provisions in continental Latin
      America. DESIGN: Information on regulations of service hours was extracted from
      either the national transportation authorities or ministries of transportation
      (or the equivalent institution) from each country. SETTING: Seventeen sovereign
      countries in continental Latin America (Argentina, Bolivia, Brazil, Chile,
      Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico,
      Nicaragua, Panama, Paraguay, Peru, Uruguay, Venezuela). PARTICIPANTS: N/A
      INTERVENTION (IF ANY): N/A MEASUREMENT: Data on (a) limit on work hours, (b)
      mandatory daily time off (or rest), (c) overall schedule (mandatory weekly time
      off), and (d) daily breaks were extracted and summarized. RESULTS: Of the 17
      countries surveyed, 9 countries have provisions limiting the daily amount of
      hours of service for professional drivers. Ten have provisions for mandatory
      daily rest, but only 5 have explicit provisions limiting the number of continuous
      working days, with mandatory uninterrupted time off >35 hours. Eight countries
      have provisions for mandatory breaks that limit the hours of continuous driving
      (ranging from 3 to 5:30 hours). CONCLUSION: Regulations that govern a population
      with 6 million injuries and over 100,000 deaths per year due to motor vehicle
      accidents leave important gaps. A minority, 6, of the countries regulated all 3
      aspects; daily hours, breaks, and time off, and 3 regulate none of these. The
      regulations are less precise and restrictive than those in high-income countries,
      despite the doubled road injury mortality, and likely expose professional drivers
      and other road users to an increased risk of fatigue-related accidents.

PMID- 30241664
TI  - Sleep and neurobehavioral performance vary by work start time during non
      traditional day shifts.
AB  - INTRODUCTION: It is established that shiftwork causes sleep loss and circadian
      misalignment. Individuals who work non-traditional day shifts that encroach into
      typical sleep times, such as those in the service and transportation sectors, may
      also experience sleep and circadian disruption. We aimed to determine how
      neurobehavioral performance and sleep would be affected by work start time among
      individuals working a non-traditional daytime shift pattern. METHODS: We
      collected sleep diaries, wrist-worn actigraphy (CamNtech, Cambridge UK), and the
      psychomotor vigilance task (PVT) from 44 pilots (4F) who worked a shift rotation
      consisting of a five-day baseline block starting in the mid-morning (baseline),
      five early shifts (early), five high workload midday shifts (midday), and five
      days of late shifts (late), each separated by 3-4 days off. RESULTS: Mixed-model
      analysis revealed that individuals obtained less sleep when working the early
      shifts (5.70 +/- 0.73 h) relative to baseline (6.78 +/- 0.86 h; P < .01). Sleep
      duration declined significantly from the beginning to the end of late shifts (P =
      .003). All shifts were associated with decreased reaction time on the PVT
      relative to baseline (236 +/- 48; early, 257 +/- 70 ms; midday 261 +/- 62 ms;
      late 266 +/- 64 ms; P < .01 for all). CONCLUSIONS: We found that non-traditional
      day shifts encroach on an individual's sleep opportunity and such shifts could be
      a contributing factor to the high prevalence of sleep deficiency observed in
      modern society. Our findings suggest that it would be prudent for industries
      requiring such shifts to expand fatigue risk management training to individuals
      classified as day shift workers.

PMID- 30241665
TI  - Better previous night sleep is associated with less next day work-to-family
      conflict mediated by higher work performance among female nursing home workers.
AB  - OBJECTIVES: Cross-sectional research has found that shorter and poorer sleep are
      associated with lower work performance and greater work-to-family conflict
      (WTFC). However, we know little about daily mechanisms linking sleep, work
      performance, and WTFC. This study tested whether previous nights' sleep was
      linked to next day WTFC, mediated by work performance. DESIGN: Daily interview
      methodology. SETTING: US extended-care workplaces. PARTICIPANTS: One hundred
      seventy-one female employees with children aged 9 to 17 years. MEASUREMENTS: In
      telephone interviews on 8 consecutive evenings, participants reported their daily
      work performance (work productivity, work quality), WTFC (e.g., "how much did
      things you wanted to do at home not get done because of the demands your job put
      on you?"), and previous nights' sleep duration (in hours) and sleep quality (1 =
      very badly, 4 = very well). RESULTS: Multilevel models revealed a significant
      association between previous night's sleep with next-day work performance. More
      specifically, on days following better sleep quality than usual, participants
      reported better work productivity than usual. Moreover, higher work productivity
      was associated with less WTFC on that day. A mediation test revealed that poorer
      previous night's sleep quality predicted less work productivity the next day,
      which, in turn, predicted more WTFC on the same day. CONCLUSION: Results provide
      evidence for the downward spiral of resource losses starting from poor sleep.
      Better quality sleep, as a replenished resource, may promote next-day
      productivity at work, which may bring less interference from work to the home.

PMID- 30241666
TI  - Usefulness of Estimated Plasma Volume at Postdischarge Follow-Up to Predict
      Recurrent Events in Patients With Heart Failure.
AB  - Hospital readmission for patients admitted with heart failure is a persistent
      problem. Better identification of patients at high risk of readmission for volume
      overload could have clinical implications. We evaluated estimated plasma volume
      (ePV), a marker of congestion, to predict readmission for patients seen early
      after discharge for heart failure. We identified patients hospitalized with a
      primary heart failure diagnosis and were then seen in a postdischarge clinic. We
      assessed clinical factors, ePV (derived from hemoglobin and hematocrit), and B
      type natriuretic peptide (BNP). The primary outcome was death or readmission for
      heart failure within 90 days of discharge. We identified 218 patients, of whom
      23% experienced the primary outcome. No clinical variables at time of admission
      were different between those who did and did not experience the primary outcome,
      nor were BNP (1,581 vs 1,267 pg/ml, p = 0.33) or ePV (6.00 vs 5.80, p = 0.36). At
      clinic follow-up, both BNP (1,164 vs 636, p = 0.002) and ePV (6.18 vs 5.58, p =
      0.02) were higher in those with subsequent events. Kaplan-Meier survival analysis
      showed that the lowest tertile of ePV had significantly lower incidence of the
      primary outcome than the other 2 tertiles (12% vs 29% and 27%, p = 0.02).
      Estimated plasma volume remained independently predictive of outcomes after
      controlling for BNP (p <0.05). In conclusion, EPV may be predictive of death or
      hospital readmission in heart failure patients seen soon after discharge,
      independent of BNP. Its potential warrants future prospective research evaluating
      its utility in larger heart failure cohorts.

PMID- 30241667
TI  - Corrigendum to "Identifying localized and scale-specific multivariate controls of
      soil organic matter variations using multiple wavelet coherence" [Sci. Total
      Environ. 643 (2018) 548-558].

PMID- 30241668
TI  - Risk of Coronary Artery Disease in Patients With Systemic Lupus Erythematosus: A
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: The association between chronic inflammation and the accelerated
      development of atherosclerosis is well recognized. However, it remains
      controversial as to whether the risk of coronary artery disease (CAD) is elevated
      in patients with systemic lupus erythematosus (SLE). The objective of this meta
      analysis was to obtain a better estimate of the risk of CAD in patients with SLE.
      METHODS: An English-restricted literature review was conducted according to
      PRISMA guidelines using key databases, surveying all articles published through
      October 31, 2017. Specific search terms included "SLE" and "coronary artery
      disease" as well as appropriate MeSH terms. The Newcastle-Ottawa scale was used
      for quality assessment. RESULTS: Nine studies were identified and included in
      this meta-analysis. The pooled risk ratio of CAD in patients with SLE was 3.39
      (95% CI: 2.15-5.35). The statistical heterogeneity of this meta-analysis was
      high, with an I2 value of 79.5%. An elevated risk of CAD was consistently
      observed in both female and male SLE patients (pooled risk ratio: 3.27 [95% CI:
      2.01-5.30] and 3.16 [95% CI: 2.02-4.94], respectively). CONCLUSIONS: SLE patients
      are at significantly higher risk of developing CAD. However, as relatively few
      studies were available for incorporation into this meta-analysis, there is a
      clear need for further studies with larger sample sizes that better parse gender
      related differences in CAD susceptibility among SLE patients. Future work to
      standardize cardiovascular risk factor identification and monitoring in SLE
      patients is also needed.

PMID- 30241669
TI  - Mitigation of Stroke Risk in Nonvalvular Atrial Fibrillation Patients With High
      Grade Carotid Artery Stenosis.

PMID- 30241671
TI  - Utility of indocyanine green for intra-operative localization of ureter in
      complex colo-rectal surgery.

PMID- 30241670
TI  - Tuberculosis of the elbow: A rare form of presentation of extrapulmonary
      tuberculosis.

PMID- 30241672
TI  - Perianal Paget disease.

PMID- 30241673
TI  - Neurological deficit after transsphenoidal surgery.

PMID- 30241674
TI  - Placental metabolism and disease.

PMID- 30241675
TI  - Corrigendum to "Potassium ions in extender differentially influence the post-thaw
      sperm motility of salmonid fish" [Cryobiology 73(2) (2016) 248-256].

PMID- 30241676
TI  - Introduction to the joint British Society of Gastroenterology (BSG) and
      Healthcare Infection Society (HIS) faecal microbiota transplant guidelines.

PMID- 30241677
TI  - Expression pattern of galectin-1 and galectin-3 in rat testes and epididymis
      during postnatal development.
AB  - Galectins are a family of lectins-binding beta-galactosides involved in a variety
      of extracellular and intracellular processes, thereby contributing to
      homeostasis, cell adhesion, cellular turnover, and immunity. This study aimed to
      determine the localization and expression of galectin-1 (Gal-1) and galectin-3
      (Gal-3) in the testis and epididymis of rats at postnatal [(prepubertal (day 5),
      pubertal (day 20), postpubertal (day 50) and mature (day 70)] periods by using
      immunohistochemistry and Western blotting. Gal-1 and Gal-3 were differentially
      expressed in different types of cells in the testis and epididymis during
      postnatal development. While we detected Gal-1 expression in some spermatogenic
      cells and Leydig cells in the testis, not in the epididymal epithelium, Gal-3 was
      expressed in Sertoli cells, peritubular myoid cells, Leydig cells, smooth muscles
      and interstitial CD68-positive macrophages. Epithelial cells of the corpus and
      cauda epididymis showed an intense Gal-3 expression. Gal-1 expression was higher
      in the testis than in the epididymis on days 50 and 70. The expression of Gal-3
      in the testis increased from the prepubertal to mature period. While the
      expression difference of Gal-3 was not statistically significant in the testis
      and epididymis until puberty, Gal-3 expression in the postpubertal and mature
      periods was higher in the epididymis. The expression of Gal-3 in the corpus and
      cauda epididymis was higher than that in the caput epididymis. In conclusion, our
      findings suggest that puberty has potential regulatory effect on the expression
      of galectins in testis and epididymis of rats. Gal-1 and 3 may play a role in the
      development of the reproductive system and the preservation of the immune
      privileged environment in the testis, due to their pro-apoptotic and anti
      apoptotic functions. The presence of intense expression of Gal-3 in the corpus
      and cauda epididymis may contribute to the maturation and storage of spermatozoa.

PMID- 30241679
TI  - Debris Removal from the Mesial Root Canal System of Mandibular Molars with Laser
      activated Irrigation.
AB  - INTRODUCTION: The purpose of this study was to compare in vitro the canal and
      isthmus debridement of manual-dynamic, passive ultrasonic, and laser-activated
      irrigation with an Er:YAG laser in mesial roots of human mandibular molars.
      METHODS: Fifty extracted mandibular molars with an isthmus were embedded in resin
      and sectioned axially 4 mm from the apex. The teeth were reassembled with guide
      pins and bolts, and the mesial canals were instrumented up to a ProTaper F2
      rotary file (Dentsply Maillefer, Ballaigues, Switzerland). Teeth were randomly
      assigned to the following irrigant activation groups (n = 10): conventional
      needle irrigation (NI), manual-dynamic irrigation with a ProTaper F2 gutta-percha
      cone, ultrasonically activated irrigation using a size 20 Irrisafe (Satelec
      Acteon, Merignac, France), and laser-activated irrigation (LAI) with an Er:YAG
      laser and a conical 400-MUm fiber tip in the canal entrance or a 600-MUm tip over
      the canal entrance. Root cross-sectional images were taken before and after final
      irrigation, and the area occupied by debris in the main canal and the isthmus was
      determined using image analysis software. Differences in debris before and after
      activation were statistically compared within and across groups. RESULTS:
      Significant reductions in debris levels were observed in all groups, except for
      NI and manual-dynamic irrigation (canal only). None of the methods rendered the
      canal systems debris free. In the canal, LAI with an Er:YAG laser and a 600-MUm
      tip over the canal entrance removed significantly more debris than NI. In the
      isthmus, LAI with an Er:YAG laser and a conical 400-MUm fiber tip in the canal
      entrance removed significantly more debris than NI. CONCLUSIONS: Within the
      limitations of this in vitro study, canal and isthmus cleanliness significantly
      improved after irrigant activation.

PMID- 30241678
TI  - Structural and Biophysical Characterization of Rab5a from Leishmania Donovani.
AB  - Leishmania donovani possess two isoforms of Rab5 (Rab5a and Rab5b), which are
      involved in fluid phase and receptor-mediated endocytosis, respectively. We have
      characterized the solution structure and dynamics of a stabilized truncated
      LdRab5a mutant. For the purpose of NMR structure determination, protein stability
      was enhanced by systematically introducing various deletions and mutations.
      Deletion of hypervariable C-terminal and the 20 residues LdRab5a specific insert
      slightly enhanced the stability, which was further improved by C107S mutation.
      The final construct, truncated LdRab5a with C107S mutation, was found to be
      stable for longer durations at higher concentration, with an increase in melting
      temperature by 10 degrees C. Solution structure of truncated LdRab5a shows the
      characteristic GTPase fold having nucleotide and effector binding sites.
      Orientation of switch I and switch II regions match well with that of guanosine
      5'-(beta, gamma-imido)triphosphate (GppNHp)-bound human Rab5a, indicating that
      the truncated LdRab5a attains the canonical GTP bound state. However, the
      backbone dynamics of the P-loop, switch I, and switch II regions were slower than
      that observed for guanosine 5'-(beta, gamma-imido)triphosphate (GMPPNP)-bound H
      Ras. This dynamic profile may further complement the residue-specific
      complementarity in determining the specificity of interaction with the effectors.
      In parallel, biophysical investigations revealed the urea induced unfolding of
      truncated LdRab5a to be a four-state process that involved two intermediates, I1
      and I2. The maximal 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (Bis-ANS)
      binding was observed for I2 state, which was inferred to have molten globule like
      characteristics. Overall, the strategy presented would have significant impact
      for studying other Rab and small GTPase proteins by NMR spectroscopy.

PMID- 30241680
TI  - Prevalence of Candida Species in Endodontic Infections: Systematic Review and
      Meta-analysis.
AB  - INTRODUCTION: Candida in endodontic infections has been investigated in a large
      number of studies, but its role as an endodontic pathogen is still debatable. The
      aim of this study was to systematically review the literature on the prevalence
      of Candida species in root canal infections. METHODS: Extensive literature
      research was performed in the most important electronic biomedical databases, and
      additional studies have been identified from references from relevant articles.
      Studies were critically appraised using a modified version of the Joanna Briggs
      Institute Critical Appraisal Checklist. RESULTS: From 2225 unique records, 2118
      were excluded on the basis of title and abstract. Of the remaining 107 studies,
      50 were excluded after full-text review, and 57 were included for qualitative and
      quantitative analysis. The overall prevalence of Candida spp. in root canal
      infections was 8.20% (95% confidence interval, 5.56%-11.21%). Candida albicans
      was the most frequently isolated species. Significant heterogeneity among studies
      was observed (P < .001, I2 = 86.07%). Subgroup analyses revealed a higher
      prevalence of Candida spp. from African samples. All studies considered, a high
      or unclear risk of bias was prevalent regarding 6 out of the 8 items considered
      in the critical appraisal. CONCLUSIONS: Candida spp. occurred in a small
      proportion of root canal infections. Further and better designed research is
      needed to investigate the real contribution of Candida spp. to the microbial
      ecology in infected root canals.

PMID- 30241681
TI  - Enhancing Effect of Elastinlike Polypeptide-based Matrix on the Physical
      Properties of Mineral Trioxide Aggregate.
AB  - INTRODUCTION: Elastinlike polypeptide (ELP) is 1 of the genetically engineered,
      protein-based polypeptides, which offers outstanding advantages such as superior
      biocompatibility, long-term stability, elasticity, and cost-effectiveness. This
      study aimed to investigate the effect of an ELP-based matrix on the physical
      properties and biocompatibility of mineral trioxide aggregate (MTA). METHODS: The
      2 types of ELPs were synthesized and mixed with the MTA powder in various liquid
      to-powder ratios. The physical properties including compressive strength,
      microhardness and setting time, washout resistance, and biocompatibility were
      investigated for the ELP-incorporated MTA. The microstructure of the MTA was also
      analyzed using scanning electron microscopy and Fourier-transform infrared
      spectroscopy. RESULTS: The ELP-based matrix enhanced the physical properties of
      MTA, including the compressive strength, microhardness, and washout resistance of
      MTA. The ELP incorporation showed no negative effect on biocompatibility.
      However, ELPs prolonged the setting time of MTA. CONCLUSIONS: These results
      suggested that the addition of the ELP-based matrix to MTA enhanced the physical
      properties without negatively affecting the chemical structure and
      biocompatibility of MTA. Further investigation is warranted to overcome a
      clinical challenge associated with the extended setting time caused by the
      addition of ELP.

PMID- 30241682
TI  - Dental Pulp Response to RetroMTA after Partial Pulpotomy in Permanent Human
      Teeth.
AB  - INTRODUCTION: A lack of information exists regarding the efficacy of RetroMTA
      (BioMTA, Seoul, Korea) directly applied on the pulp in vital pulp therapy. This
      study was designed to examine the clinical efficacy of RetroMTA compared with
      ProRoot mineral trioxide aggregate (MTA) (Dentsply Tulsa Dental, Tulsa, OK) for
      partial pulpotomy. METHODS: Partial pulpotomy was performed in 22 healthy human
      maxillary and mandibular third molars planned for extraction. The teeth were
      randomly divided into 2 groups (n = 11) and underwent partial pulpotomy with
      RetroMTA and ProRoot MTA as the control. The teeth were then restored with glass
      ionomer cement. Clinical and electric pulp tests were performed after 1 and 8
      weeks. The teeth were radiographed and extracted at 8 weeks. Histologic sections
      were prepared and analyzed for pulp inflammation and dentinal bridge formation.
      Data were analyzed using the Mann-Whitney U test. RESULTS: Clinical examination
      after 1 and 8 weeks showed no sensitivity to heat, cold, or palpation in the
      ProRoot MTA and RetroMTA groups. Periapical radiographs taken before the
      extraction of teeth showed no evidence of periapical pathology. Electric pulp
      testing revealed no sensitivity. Data comparisons using the Mann-Whitney U test
      showed no significant difference between the materials with regard to the pulp
      inflammation type, intensity and extension (P = .3), or bridge continuity (P =
      .12). However, these data revealed a significant difference between the 2
      materials in pulp morphology (P < .05) and bridge thickness (P < .01).
      CONCLUSIONS: This is the first work to evaluate a RetroMTA histologic outcome in
      partial pulpotomy in human permanent teeth. It shows pulp disorganization, an
      absence of inflammation, and discontinuous mineralization, which may represent a
      potential drawback with RetroMTA in this indication.

PMID- 30241683
TI  - [Introduction-Epidemiology of latent and active tuberculosis].

PMID- 30241684
TI  - Maternal antibody inhibition of recombinant Newcastle disease virus vectored
      vaccine in a primary or booster avian influenza vaccination program of broiler
      chickens.
AB  - Maternally-derived antibodies (MDA) provide early protection from disease, but
      may interfere with active immunity in young chicks. In highly pathogenic avian
      influenza virus (HPAIV)-enzootic countries, broiler chickens typically have MDA
      to Newcastle disease virus (NDV) and H5 HPAIV, and their impact on active
      immunity from recombinant vectored vaccines is unclear. We assessed the
      effectiveness of a spray-applied recombinant NDV vaccine with H5 AIV insert (rNDV
      H5) and a recombinant turkey herpesvirus (HVT) vaccine with H5 AIV insert (rHVT
      H5) in commercial broilers with MDA to NDV alone (MDA:AIV-NDV+) or to NDV plus
      AIV (MDA:AIV+NDV+) to provide protection against homologous HPAIV challenge. In
      Experiment 1, chicks were spray-vaccinated with rNDV-H5 at 3 weeks (3w) and
      challenged at 5 weeks (5w). All sham-vaccinated progeny lacked AIV antibodies and
      died following challenge. In rNDV-H5 vaccine groups, AIV and NDV MDA had
      completely declined to non-detectable levels by vaccination, enabling rNDV-H5
      spray vaccine to elicit a protective AIV antibody response by 5w, with 70-78%
      survival and significant reduction of virus shedding compared to shams. In
      Experiment 2, progeny were vaccinated with rHVT-H5 and rNDV-H5 at 1 day (1d) or
      3w and challenged at 5w. All sham-vaccinated progeny lacked AIV antibodies and
      died following challenge. In rHVT-H5(1d) vaccine groups, irrespective of rNDV
      H5(3w) boost, AIV antibodies reached protective levels pre-challenge, as all
      progeny survived and virus shedding significantly decreased compared to shams. In
      contrast, rNDV-H5-vaccinated progeny had AIV and/or NDV MDA at the time of
      vaccination (1d and/or 3w) and failed to develop a protective immune response by
      5w, resulting in 100% mortality after challenge. Our results demonstrate that MDA
      to AIV had minimal impact on the effectiveness of rHVT-H5, but MDA to AIV and/or
      NDV at the time of vaccination can prevent development of protective immunity
      from a primary or booster rNDV-H5 vaccine.

PMID- 30241685
TI  - Bariatric Surgery Needs a Seat at the Children's Table: Bridging the Perception
      and Reality of the Role of Bariatric Surgery in the Treatment of Obesity in
      Adolescents.
AB  - The long-term morbidity of obesity in adolescents is well recognized nationally
      and represents a major health concern for the population of the near future.
      Traditional medical management of obesity focuses on addressing behavioral
      modification, dietary and exercise programs, and, to a lesser degree,
      pharmaceuticals. Although these strategies are relatively effective, they suffer
      from the lack of sustained benefit, a high relapse rate, and, in case of
      pharmacotherapy, potentially dangerous adverse effects. Bariatric surgery in
      adolescents has often been characterized as a risky intervention with unknown
      long-term benefits. However, recent data establish that a sustained, clinically
      meaningful effect on weight loss, as well as a reduction in chronic morbidities
      related to obesity, can be achieved. The role of bariatric surgery as an accepted
      adjunctive strategy in the treatment of obesity in adolescents is becoming more
      recognized; however, a number of barriers exist that prevent the timely
      evaluation of adolescents with obesity for potential surgical intervention. We
      examine these barriers in light of recent advancements to help better define the
      role of bariatric surgery in the treatment of obesity in adolescent population.

PMID- 30241686
TI  - Maternal BMI, Mid-pregnancy Fatty Acid Concentrations,and Perinatal Outcomes.
AB  - PURPOSE: Maternal body mass index (BMI) and systemic fatty acid (FA)
      concentrations affect inflammatory balance in pregnancy and play a key role in
      fetal growth and well-being. Little is known about how maternal BMI may affect
      the association between key FA concentrations and neonatal outcomes. The
      objective of this study was to examine the associations between the maternal
      omega (n)6:n3 FA ratio and neonatal outcomes according to maternal pre-pregnancy
      BMI category. METHODS: This study is a secondary analysis of the Maternal-Fetal
      Medicine Units Network randomized controlled trial of omega-3 FA supplementation
      to prevent recurrent preterm birth. At consent (16-22 weeks of pregnancy), women
      were randomized to either the intervention arm (2g of n3 FAs) or the control arm
      (placebo). For the present analysis, the primary exposure was the ratio of
      proinflammatory to anti-inflammatory (n6:n3) FAs at 25 to 28 weeks of pregnancy.
      The primary outcome was fetal growth as measured by using birth-weight-for
      gestational-age z score, birth-length-for-gestational-age z score, and head
      circumference-for-gestational-age z score. BMI categories were defined as lean
      (18.5-24.9 kg/m2) and overweight/obese (OWOB) (>=25.0 kg/m2). Final analysis was
      stratified according to BMI and adjusted for education, race, parity, smoking
      status, total fish intake at the time of the blood draw, and number of days in
      the study at the time of delivery. FINDINGS: A total of 440 participants were
      included in this analysis; 49% were lean, and 51% were OWOB. After adjustment for
      covariates, a higher maternal n6:n3 FA ratio was associated with impaired fetal
      growth (birth-weight-for-gestational-age z score, beta = -0.04 per unit increase
      in n6:n3; 95% CI, -0.07 to -0.01), 1day shorter length of gestation (beta = -0.14
      week; 95% CI, -0.27 to -0.01), higher incidence of neonatal respiratory distress
      syndrome (odds ratio, 1.37; 95% CI, 1.04 to 1.80), and increased length of
      neonatal hospital stay (beta = 0.29 day; 95% CI, 0.003 to 0.58) in OWOB, but not
      lean, participants. IMPLICATIONS: Higher maternal inflammation during pregnancy,
      as measured by using the n6:n3 FA ratio, may be a marker of adverse perinatal and
      neonatal outcomes, particularly among OWOB women.

PMID- 30241687
TI  - Lack of a Clinically Significant Pharmacokinetic Interaction Between Pregabalin
      and Thioctic Acid in Healthy Volunteers.
AB  - PURPOSE: Pregabalin and thioctic acid are likely to be used concomitantly for the
      treatment of painful diabetic neuropathy. In this study, the pharmacokinetic
      interaction between pregabalin and thioctic acid was investigated at steady
      state. METHODS: A randomized, open-label, 6-sequence, 3-period, 3-treatment
      crossover study was conducted in 42 healthy male volunteers. The volunteers
      randomly received pregabalin 300 mg BID for 6 times, thioctic acid 600 mg once
      daily for 3 times, or the combination of pregabalin and thioctic acid. Serial
      blood samples were collected up to 24 hours after the last dosing in each period.
      Pharmacokinetic parameters were calculated by using noncompartmental analysis
      methods. FINDINGS: The mean concentration-time curves were similar between each
      drug alone and in combination with the other drug. The 90% CIs of the geometric
      mean ratios with and without the co-administered drug for Cmax at steady state
      and AUC during the dosing interval were well within the conventional
      bioequivalence range of 0.8 to 1.25, except for Cmax at steady state for thioctic
      acid, which barely exceeded only the lower bound (0.78-1.15). Co-administered
      pregabalin and thioctic acid was well tolerated. IMPLICATIONS: Repeatedly
      administered pregabalin and thioctic acid do not interact pharmacokinetically.
      This study suggests that the combination of pregabalin and thioctic acid can
      safely be administered concomitantly without dose adjustment. ClinicalTrials.gov
      identifier: NCT01808300.

PMID- 30241688
TI  - Bioavailability of Edaravone Sublingual Tablet Versus Intravenous Infusion in
      Healthy Male Volunteers.
AB  - PURPOSE: Edaravone is a free-radical scavenger. Edaravone 30mg IV has been
      approved for use in the treatment of acute ischemic stroke in Japan and China,
      and for amyotrophic lateral sclerosis in Japan and the United States. Considering
      the inconvenience of IV infusion in clinical practice, an oral tablet formulation
      of edaravone was developed but failed in 2011 due to poor bioavailability. More
      recently, a sublingual (SL) tablet formulation of edaravone 30mg was developed by
      a Good Manufacturing Practices-compliant manufacturer in China. This study
      explored the bioavailability of the SL tablet of edaravone and aimed to provide
      evidence to support decision making in future clinical development. METHODS: This
      2-way crossover study was conducted in 10 healthy male volunteers. Eligible
      subjects were randomized, in a 1:1 ratio, to 1 of 2 dosing sequences: (1) SL
      edaravone 30mg, followed by edaravone 30mg IV infusion given over 30 minutes; or
      (2) edaravone 30mg IV infusion given over 30 minutes, followed by SL edaravone
      30mg. The washout period between the 2 dosing periods was at least 24hours.
      Serial blood samples were collected in each dosing period. The bioavailability of
      the SL tablet was assessed using bioavailability analysis. Tolerability was
      evaluated throughout the study. FINDINGS: The plasma concentration-time profile
      of the SL tablet was similar to that with the IV infusion. Amean (SD) Cmax of
      2030.2 (517.2) ng/mL was reached within a median Tmax of 0.875hour, which was
      statistically significantly longer than the median Tmax with IV administration
      (0.5 hour). The Cmax with SL administration corresponded to 83.92% (90% CI,
      73.22%-96.18%) of the Cmax with the start of IV infusion (2354.0 [336.6] ng/mL).
      The mean AUC0-t with SL dosing was 5420.07 (1429.75) h . ng/mL, which
      corresponded to 91.94% (90% CI, 86.81%-97.39%) of the AUC0-t with IV
      administration (5824.42 [1338.48] h . ng/mL). Two cases of adverse events were
      reported during the study; both were considered by the investigator to have been
      possibly not related to the study treatment. IMPLICATIONS: The bioavailability of
      the SL tablet of edaravone was 91.94%. Compared with IV administration, Cmax with
      SL administration was ~17% lower and Tmax was statistically significantly longer.
      The exposure differences can be addressed by modifying the strength of the SL
      tablet, and then conducting a second study to demonstrate the pharmacokinetic
      bioavailability of the sublingually administered new strength versus IV infusion
      of edaravone.

PMID- 30241689
TI  - Recommendations on non-Pharmacological Treatment in Chronic Obstructive Pulmonary
      Disease From the Spanish COPD Guidelines (GesEPOC 2017).
AB  - Non-pharmacological treatment is essential in patients with chronic obstructive
      pulmonary disease (COPD), but this treatment is sometimes not given the
      importance it deserves. Patients diagnosed with COPD should benefit from
      comprehensive care services. These services comprise a protocolized set of
      actions aimed at covering the health needs of the patient, taking into account
      their environment and circumstances. Pulmonary rehabilitation is one of the
      essential components of non-pharmacological treatment in comprehensive COPD care
      services. In the Spanish COPD Guidelines (GesEPOC) 2017, we provided a systematic
      report of the scientific evidence for pulmonary rehabilitation programs in acute
      and stable phase disease. Another important issue in the non-pharmacological
      treatment of COPD is physical activity, and the most essential considerations
      regarding prescription are described in the GesEPOC guidelines, along with a
      review of the most effective strategies to ensure adherence. GesEPOC 2017 aims to
      underline the importance of non-pharmacological treatment as a co-adjuvant to
      pharmacological treatment.

PMID- 30241691
TI  - Intraoperative Diagnosis of Atrial Flutter Using Left Atrial Appendage Doppler
      Profiling.

PMID- 30241690
TI  - Cross-sectional survey on disease severity in Japanese patients with harlequin
      ichthyosis/ichthyosis: Syndromic forms and quality-of-life analysis in a
      subgroup.
AB  - BACKGROUND: Congenital ichthyoses (CIs) adversely affect quality of life (QOL) in
      patients. However, the effects of CIs on patient QOL have not been studied
      sufficiently. OBJECTIVE: To investigate the association between disease severity
      and QOL in patients with harlequin ichthyosis (HI) and ichthyosis: syndromic
      forms (ISFs) METHODS: Clinical information of patients with HI and ISFs from 2010
      to 2015 were obtained from 100 dermatology departments/divisions of principal
      institutes/hospitals throughout Japan. We examined the relationship between
      disease severity and QOL in patients with HI and ISFs. Patients who were aged 8
      years or older and participated in a multicenter retrospective questionnaire
      survey in Japan were assessed by dermatology life quality index (DLQI, range of 0
      30) and clinical ichthyosis score (range of 0-100). RESULTS: Netherton syndrome
      patients had a significantly higher risk of allergy to food or environmental
      allergens than patients with other phenotypes. Keratitis-ichthyosis-deafness
      (KID) syndrome patients showed a significantly higher risk of skin infections
      than patients with other phenotypes. Complete data on DLQI were obtained from 13
      patients, whose median age was 21 (8-71) years. Nine patients were male, and 4
      were female. Systemic retinoids were administrated to 2 of the 3 HI patients. The
      Spearman's correlation coefficient between the clinical ichthyosis score and DLQI
      was 0.611 (P < 0.05). CONCLUSION: We confirmed that Netherton syndrome and KID
      syndrome patients have a higher risk of allergy to food or environmental
      allergens and of skin infections, respectively. QOL impairment correlates with
      disease severity in HI and ISFs patients.

PMID- 30241693
TI  - Decline in severe spastic cerebral palsy at term in Denmark 1999-2007.
AB  - AIM: To analyse trends in prevalence and severity of cerebral palsy (CP) in
      Denmark in birth years 1999-2007 and compare with previous periods. METHOD: Data
      has been collected uniformly in the Danish cerebral palsy national register
      nationwide since 1995. Rates in the time periods 1999-2001, 2002-2004 and 2005
      2007 covering 585,393 births were analysed by gestational age and subtypes.
      RESULTS: Total number of CP cases in the period was 1165. The overall prevalence
      of CP decreased significantly from 2.1 in 1999-2001 to 1.8 in 2005-2007 per 1000
      livebirths (p = 0.022). The decline was only significant for children born at
      term (p = 0.007) but not for the preterm (p = 0.44). The decline in children born
      at term was based on a decrease in bilateral spastic CP (n = 117 in years 1999
      2001 and n = 59 in 2005-2007). Multidisciplinary obstetric skills training with
      neonatal resuscitation in Denmark was initiated in 2003 and timely associated
      with the decrease. The prevalence of unilateral spastic CP the prevalence did not
      change, but in the two last time periods more children had a right-sided than
      left-sided unilateral spastic CP. CONCLUSION: The decline in rate of CP seen in
      2005-2007 as compared to 1999-2001 was mainly based on fewer cases of severe
      spastic CP in term infants. We hypothesize that improved neonatal resuscitation
      in the delivery room may be partly responsible for the decrease. In premature
      children the decline was not significant in this time period, but has been
      dramatically decreasing in the years before the time period here analysed.

PMID- 30241692
TI  - T follicular helper cells restricted by IRF8 contribute to T cell-mediated
      inflammation.
AB  - The follicular helper T cell (TFH) are established regulators of germinal center
      (GC) B cells, whether TFH have pathogenic potential independent of B cells is
      unknown. Based on in vitro TFH cell differentiation, in vivo T cell transfer
      animal colitis model, and intestinal tissues of inflammatory bowel disease (IBD)
      patients, TFH and its functions in colitis development were analyzed by FACS,
      ChIP, ChIP-sequencing, WB, ELISA and PCR. Herein we demonstrate that intestinal
      tissues of patients and colon tissues obtained from Rag1-/- recipients of naive
      CD4+ T cells with colitis, each over-express TFH-associated gene products.
      Adoptive transfer of naive Bcl6-/- CD4+ T cells into Rag1-/- recipient mice
      abrogated development of colitis and limited TFH differentiation in vivo,
      demonstrating a mechanistic link. In contrast, T cell deficiency of interferon
      regulatory factor 8 (IRF8) resulted in augmentation of TFH induction in vitro and
      in vivo. Functional studies showed that adoptive transfer of IRF8 deficient CD4+
      T cells into Rag1-/- recipients exacerbated colitis development associated with
      increased gut TFH-related gene expression, while Irf8-/-/Bcl6-/- CD4+ T cells
      abrogated colitis, together indicating that IRF8-regulated TFH can directly cause
      colon inflammation. Molecular analyses revealed that IRF8 suppresses TFH
      differentiation by inhibiting transcription and transactivation of the TF IRF4,
      which is also known to be essential for TFH induction. Our documentation showed
      that IRF8-regulated TFH can function as B-cell-independent, pathogenic, mediators
      of colitis suggests that targeting TFH could be effective for treatment of IBD.

PMID- 30241695
TI  - Editorial overview: New technologies: multidisciplinary evolutions for drug
      discovery.

PMID- 30241694
TI  - Uptake and metabolism of mizoribine, an immunosuppressant, in L5178Y-R mouse
      lymphoma cells in vitro and peripheral blood mononuclear cells of rats and kidney
      transplant recipients in vivo.
AB  - The cellular uptake of mizoribine (MZR), an immunosuppressant, and metabolism of
      MZR to MZR-5'- monophosphate (MZRP), an active metabolite, were evaluated in
      L5178Y-R mouse lymphoma cells and peripheral blood mononuclear cells (PBMCs) of
      rats and kidney transplant recipients (KTRs, n = 22). Real-time PCR analysis
      revealed the expression of ENT1 and ENT2 mRNAs, but not of CNTs, in L5178Y-R
      cells and rat's PBMCs. In L5178Y-R cells, the uptake of MZR was suppressed by
      adenosine, a substrate for ENT1 and ENT2, but not by 5-(4-nitrobenzyl)-6
      thioinosine (0.1 MUM), an ENT1 inhibitor. Saturable metabolism of MZR to MZRP was
      observed. In rats, peak plasma concentrations of MZR and peak concentrations of
      MZR and MZRP in PBMCs were observed 3 h after oral administration. MZR
      disappeared from PBMCs in parallel with plasma MZR, but the disappearance of MZRP
      from PBMCs appeared to be slow. In KTRs, the mean plasma concentration of MZR 3-4
      h after ingestion was 3.14 MUg/ml and the mean MZRP concentration in PBMCs was
      16.8% of MZR, reflecting the involvement of ENT in the uptake of MZR. A linear
      relationship was observed between plasma MZR concentrations ranging from 1 to 6
      MUg/ml and PBMC's MZRP concentrations ranging from 90 to 200 ng/ml.

PMID- 30241696
TI  - Comparing the Detection of Endogenous Psychedelics in Individuals With and
      Without Alleged Mediumistic Experiences.
AB  - CONTEXT: Mediumship is the alleged ability to communicate with deceased
      personalities. Previous studies have suggested that the endogenous
      psychotomimetic molecules bufotenine (BT) and dimethyltryptamine (DMT) may play a
      role in the pathogenesis of psychotic disorders. Distortion of perceptions
      observed during spiritual experiences could supposedly relate to these
      substances. OBJECTIVE: To compare the presence of BT and DMT in human urine
      samples between individuals with and without mediumistic experiences. METHODS:
      All participants (5 from medium's group - MG and 5 from non-medium's group - CG)
      undertook a single night continuous 6-h urine pool collection (6:00-11:59 PM).
      Mediums collected urine samples in nights when they reported having experienced
      mediumistic communication. A sensitive high-performance liquid chromatography
      mass spectrometry (HPLC-MS) assay was used. Questionnaires were used to detect
      common mental disorders symptoms, and to screen and quantify anomalous
      experiences. RESULTS: DMT was not detected in any urine specimen tested. The
      presence of BT detection in urine samples was greater in CG (2/5) than in MG
      (1/5), with no significant differences (p > 0.99). MG reported more anomalous
      experiences than CG (6.6+/-0.8 vs. 2.2+/-1.5, p = 0.03), but there was no
      difference concerning their mental health. CONCLUSION: There were no differences
      between individuals with and without alleged mediumistic experiences concerning
      endogenous psychedelics. Both BT and DMT are highly sensitive to metabolism by
      monoamine oxidase and to N-oxidation, and do not survive in the periphery for
      long. Alternative strategies should be considered to further investigate the
      putative role of the endogenous psychedelics pathway for the spiritual
      experiences.

PMID- 30241697
TI  - Associations of cardiovascular fat radiodensity and vascular calcification in
      midlife women: The SWAN cardiovascular fat ancillary study.
AB  - BACKGROUND AND AIMS: Fat radiodensity, measured via CT Hounsfield units (HU), is
      a potential marker of fat quality. We sought to determine the cross-sectional
      associations of total heart fat (TAT) and aortic perivascular fat (PVAT)
      radiodensity with cardiovascular risk factors, coronary artery calcification
      (CAC), and aortic calcification (AC) in midlife women. METHODS: Fat radiodensity,
      CAC, and AC were quantified using CT scans. A total of 528 women (mean age: 50.9
      +/- 2.9 years; 37% Black) were included in analyses. RESULTS: Women in the lowest
      TAT radiodensity tertile were more likely to have adverse cardiovascular risk
      factors. Independent of cardiovascular risk factors, women in the middle and high
      TAT radiodensity tertiles were less likely to have CAC (OR (95% CI): 0.32 (0.18,
      0.59); 0.43 (0.24, 0.78), respectively) compared with women in the lowest TAT
      radiodensity tertile. Although adjusting for BMI attenuated the overall
      association, women in the middle TAT radiodensity tertile remained at
      significantly lower odds of CAC when compared to the low radiodensity tertile,
      0.47 (0.24, 0.93), p=0.03. No significant associations were found for PVAT
      radiodensity and calcification measures in multivariable analysis. CONCLUSIONS:
      Lower TAT radiodensity was associated with a less favorable cardiometabolic
      profile. Women with mid-range TAT radiodensity values had a lower odds of CAC
      presence, independent of CVD risk factors and BMI. More research is necessary to
      understand radiodensity as a surrogate marker of fat quality in midlife women.

PMID- 30241699
TI  - Tick-borne encephalitis (TBE) in children in Europe: Epidemiology, clinical
      outcome and comparison of vaccination recommendations.
AB  - Tick-borne encephalitis (TBE) vaccination recommendations for children residing
      in high-endemicity countries in Europe vary from universal recommendations to
      none at all. Such differences may result in uncertainty about the value of such
      prevention among public health authorities, healthcare professionals and parents.
      We conducted a systematic review of publications and data from the European
      Centres for Disease Prevention and Control focusing on the epidemiology, clinical
      characteristics, and outcomes of TBE in a pediatric population. TBE can affect
      children of any age, occasionally even before the first birthday. Overall, the
      clinical course of disease is milder compared to adults, and there are fewer
      neurologic sequelae persisting after the infection. However, recent follow-up
      surveys identified a substantial proportion of children with long-term cognitive
      impairment subsequent to TBE infection. Fortunately, two vaccines against western
      TBE are available, and both are effective and safe. It is an overly simplistic
      perception that TBE is severe in adults and mild in children, and to therefore
      conclude that vaccination is important mainly in older age groups. Even if TBE
      infection is less dramatic in pediatric populations, TBE often results in long
      standing cognitive damage. Based on guidance from the World Health Organization,
      authorities in countries with high endemicity should either offer or recommend
      TBE vaccination to children at 1-3 years of age.

PMID- 30241698
TI  - Low effective population sizes in Amblyomma variegatum, the tropical bont tick.
AB  - Effective population sizes have rarely been estimated in ticks despite the
      importance of this parameter for evaluating the evolutionary and adaptive
      potential of tick populations. The present study was aimed at evaluating the
      effective population sizes of Amblyomma variegatum, the tropical bont tick, in
      three villages in Burkina Faso. For this purpose, microsatellites markers were
      developed. Eight out of 19 assessed markers provided good amplification results
      with 4 to 24 alleles recorded per marker on 216 genotyped ticks. The within
      samples polymorphism was congruent with Hardy-Weinberg expectations at four
      markers while sex linkage and/or null alleles were observed at the others. As
      sampling involved two tick generations, effective population sizes were
      independently estimated by two methods insensitive to heterozygosity: the first
      one is based on linkage disequilibrium analysis within a single cohort while the
      second uses the changes in allele frequencies across generations. Both methods
      estimated the number of reproducing ticks ranging from two to a few tens
      reproductive adults per village and cohort. Such small estimates are congruent
      with the rarity of records of acaricide resistance in A. variegatum.

PMID- 30241700
TI  - Tuberculosis: an opportunity to integrate mental health services in primary care
      in low-resource settings.

PMID- 30241701
TI  - The reliability and validity of the Figure of 8 Walk test in older people with
      knee replacement: does the setting have an impact?
AB  - OBJECTIVE: To determine the reliability and validity of the Figure of 8 Walk test
      (F8W) for older people after knee replacement surgery in the home setting.
      DESIGN: Observational repeated measures. SETTING: A specialist orthopaedic
      hospital and participants homes. PARTICIPANTS: Seventy-four older adults aged
      over 55 years one year following knee replacement surgery participated in two
      assessments more than one week apart. MAIN OUTCOME MEASURE: The time to complete,
      steps, boundary limits and smoothness score from the Figure of 8 Walk test (F8W),
      the time to complete the Timed Up and Go (TUG) test and the time to complete the
      Timed Walk Test (TWT). RESULTS: Overall, on 95% of occasions, the difference
      between the measurements for intra-rater reliability were within 1.8second of the
      two test times. The difference between the measurements for inter-rater
      reliability were found to be narrower than for intra-rater reliability with
      scores within 1.2second overall on 95% of occasions. The time to perform the F8W
      was highly correlated to the Timed Up and Go (overall sample r=0.921) and the
      variability spread within narrow limits (-0.8 to 0.8 z-scores). This was also
      true for the Timed Walk Test (overall sample r=0.834) with a narrow limit of
      variability on almost all of the observations (-1.16 to 1.16 z-scores).
      CONCLUSIONS: The F8W test has good reliability and validity when used in either a
      clinical or home setting for patients around one year following knee replacement
      surgery.

PMID- 30241702
TI  - Maltreatment in childhood and intimate partner violence: A latent class growth
      analysis in a South African pregnancy cohort.
AB  - Intimate partner violence (IPV) is a significant global problem, prevalent in low
      and middle-income countries (LMICs). IPV is particularly problematic during the
      perinatal and early postnatal period, where it is linked with negative maternal
      and child health outcomes. There has been little examination of profiles of IPV
      and early life adversity in LMIC contexts. We aimed to characterize longitudinal
      IPV and to investigate maternal maltreatment in childhood as a predictor of IPV
      exposure during pregnancy and postnatally in a low resource setting. This study
      was nested in the Drakenstein Child Health Study, a longitudinal birth cohort.
      Maternal IPV (emotional, physical and sexual) was measured at six timepoints from
      pregnancy to two years postpartum (n = 832); sociodemographic variables and
      maternal maltreatment in childhood were measured antenatally at 28-32 weeks'
      gestation. Associations between maternal maltreatment in childhood and IPV latent
      class membership (to identify patterns of maternal IPV exposure) were estimated
      using multinomial and logistic regression. We observed high levels of maternal
      maltreatment during childhood (34%) and IPV during pregnancy (33%). In latent
      class analysis separating by IPV sub-type, two latent classes of no/low and
      moderate sexual IPV and three classes of low, moderate, and high emotional and
      physical IPV (separately) were detected. In combined latent class analysis,
      including all IPV sub-types together, a low, moderate and high exposure class
      emerged as well as a high antenatal/decreasing postnatal class. Moderate and high
      classes for all IPV sub-types and combined analysis showed stable intensity
      profiles. Maternal childhood sexual abuse, physical abuse and neglect, and
      emotional abuse predicted membership in high IPV classes, across all domains of
      IPV (aORs between 1.99 and 5.86). Maternal maltreatment in childhood was
      associated with increased probability of experiencing high or moderate intensity
      IPV during and around pregnancy; emotional neglect was associated with decreasing
      IPV class for combined model. Intervening early to disrupt this cycle of abuse is
      critical to two generations.

PMID- 30241703
TI  - Impact of adverse childhood experiences (ACEs) on adult alcohol consumption
      behaviors.
AB  - BACKGROUND: Long term negative physical and mental health problems occur from the
      lack of appropriate interventions targeting the adult population who experienced
      adverse childhood experiences (ACEs) and partake in risky alcohol consumption
      behaviors. OBJECTIVE: This study aimed to identify the risk for alcohol
      consumption behaviors, specifically binge drinking (BD) and any drinking (AD),
      among adults with a history of adverse childhood experiences (ACEs). METHODS:
      Behavioral Risk Factor Surveillance System (BRFSS) 2011-2012 data were used.
      Descriptive statistics were completed followed by simple and multiple logistic
      regression to determine the strength of association between ACEs and alcohol
      consumption, controlling for sociodemographic factors. RESULTS: The final
      adjusted sample size was 69,793. Adults who experienced household abuse were 30%
      more likely to BD (Odds Ratio (OR): 1.30, 95% Confidence Interval (CI): 1.20
      1.41) and 21% more likely for AD (OR: 1.21, 95% CI: 1.14-1.28) in the past month.
      Males were over two times more likely to BD (OR: 2.12, 95% CI: 1.96-2.29) and 60%
      more likely for AD (OR: 1.60, 95% CI: 1.51-1.69) in the past month compared to
      females. Individuals who completed some college were at higher risk of BD (OR:
      1.51, 95% CI: 1.26-1.82), whereas those who graduated college were nearly two and
      a half times more likely to report AD in the past month (OR: 2.27, 95% CI: 1.99
      2.59) compared to individuals with less than high school education. CONCLUSION:
      Adults who experienced household abuse, are male, or possess at least some
      college education are at increased risk for BD and AD.

PMID- 30241704
TI  - Food Avoidance Beliefs and Behaviors Among Chinese Cancer Patients: Validation of
      a New Measurement Tool.
AB  - OBJECTIVE: Restrictive food avoidance behavior among Chinese cancer patients is
      common. Yet, to the authors' knowledge, no study has investigated factors
      associated with such behavior. This study attempted to validate a new measurement
      tool, the Cancer Patients Food Avoidance Behaviors Scale (CPFAB), that assessed
      cancer patients' belief regarding 5 perceived benefits of practicing food
      avoidance, and to test its applicability. DESIGN: Cross-sectional face-to-face
      interviews. SETTING: Two outpatient oncology clinics in 2 different districts of
      Hong Kong. PARTICIPANTS: A total of 245 patients with nasopharyngeal and
      colorectal cancer. MAIN OUTCOME MEASURES: Assessment of psychometric properties
      of the CPFAB. ANALYSIS: Principal components method with oblique (Promax)
      rotations was performed to investigate the factor structure of the CPFAB.
      RESULTS: Psychometric properties, which included test-retest intraclass
      correlations (mean = 0.72; SD = 0.12), Cronbach alpha (.88-.94), floor (0.4% to
      5.7%) and ceiling (0% to 7.3%) effects, and item-subscale (0.67-0.79) and
      subscale-total (0.68-0.89) correlations, were satisfactory. CONCLUSIONS AND
      IMPLICATIONS: The CPFAB, a new instrument used to assess food avoidance, was
      developed and validated. It showed satisfactory psychometric properties and can
      be used to evaluate interventions that seek to modify food avoidance attitudes
      among cancer patients.

PMID- 30241705
TI  - The Role of Self-Identity in Predicting College Students' Intention to Consume
      Fruits and Vegetables.
AB  - OBJECTIVE: To identify factors influencing intention to consume fruits and
      vegetables (F&V) among college students by applying the Theory of Planned
      Behavior with the inclusion of self-identity and past behavior. DESIGN: Cross
      sectional study conducted in 2017. SETTING: Undergraduate classes at the
      University of Alabama. PARTICIPANTS: A total of 343 undergraduate students, mean
      age 20.3 years, participated in the study. MAIN OUTCOME MEASURE(S): Participants
      completed validated instruments measuring Theory of Planned Behavior variables,
      past behavior, and self-identity. ANALYSIS: Structural equation modeling was used
      to analyze the data. Overall chi-square goodness of fit, comparative fit index,
      root mean square error of approximation, and Tucker-Lewis Index were used to
      assess model fit. RESULTS: Model fit indices showed that the hypothesized
      structural equation modeling model provided a good fit to the data (chi2 =
      306.35; degrees of freedom = 104, root mean square error of approximation = 0.08;
      comparative fit index =0.95; Tucker-Lewis Index = 0.94). Self-identity was the
      most significant predictor of intention to consume fruits and vegetables,
      followed by attitude, past behavior, perceived behavioral control, and subjective
      norm among college students. CONCLUSIONS AND IMPLICATIONS: Nutrition education
      advocating the role of increased F&V consumption in positive self-identity, such
      as handouts incorporating images relatable to college students, may increase
      college students' intention to consume F&V.

PMID- 30241706
TI  - Home Environment-Focused Intervention Improves Dietary Quality: A Secondary
      Analysis From the Healthy Homes/Healthy Families Randomized Trial.
AB  - OBJECTIVE: Estimate Healthy Homes/Healthy Families (HHHF) intervention efficacy
      for improving dietary quality. METHODS: Low-income overweight and obese women (n
      = 349) recruited from rural community health centers were randomized to receive
      HHHF, a 16-week home environment-focused coaching intervention or health
      education materials by mail. Healthy Eating Index-2010 scores were calculated
      from 2 24-hour dietary recalls collected at baseline and 6- and 12-month follow
      up. RESULTS: HHHF participants reported greater improvements in Healthy Eating
      Index-2010 total scoresat 6-month follow-up (+3.41 +/- 13.43 intervention vs
      +2.02 +/- 12.26 control; P =.009). Subcomponentanalysis indicated greater
      consumption of total vegetables (P = .02) and greens and beans(P = .001), whole
      grains (P = .02) and reduced consumption of empty calories (P = .03).
      Standardizedintervention effect sizes were 0.16 at 6 months and 0.13 at 12 months
      of follow-up. CONCLUSIONS AND IMPLICATIONS: The HHHF resulted in short-term
      improvements in dietary quality, although more research is needed to interpret
      the clinical significance of effect sizes of this magnitude.

PMID- 30241708
TI  - Comparison of operating room air distribution systems using the environmental
      quality indicator method of dynamic simulated surgical procedures.
AB  - BACKGROUND: Ensuring aseptic airborne environments for sterile fields and back
      instrument tables in operating rooms (ORs) is crucial to reducing microbial and
      particle contamination during surgery. Configurations of in-ceiling air delivery
      mechanisms impact the effectiveness of the system at eliminating contamination in
      critical zones. METHODS: The environmental quality indicator method was used to
      assess airborne environments in ORs equipped with a single large diffuser (SLD),
      a multidiffuser array (MDA), or a 4-way throw diffuser during dynamic, simulated
      surgical procedures. Environmental quality indicators measured included
      particles, microbes, carbon dioxide, velocity, humidity, and temperature at 26
      air changes per hour. RESULTS: SLD ORs performed better than MDA ORs and 4-way
      throw diffuser ORs at removing microbes and carbon dioxide from the sterile field
      (P < .05). SLD ORs had higher velocity and lower temperature over the sterile
      field than the other 2 ORs (P < .05). MDA ORs had lower total particle counts
      than the other ORs (P < .05). The sterile fields in all ORs were cleaner than the
      respective back instrument tables (P < .05). CONCLUSIONS: Air delivery systems
      that eliminate blockages to uniform airflow directly over sterile zones, such as
      boom mounts and access panels, and deliver unidirectional, downward flow of clean
      filtered air provided a cleaner airborne environment within the sterile field.
      Expansion of air delivery systems to include areas outside the sterile field,
      where other surgical aides reside, may further reduce contamination within
      critical zones.

PMID- 30241707
TI  - Predictors of Overweight and Obesity in American Indian Families With Young
      Children.
AB  - OBJECTIVE: To describe sociodemographic factors and health behaviors among
      American Indian (AI) families with young children and determine predictors of
      adult and child weight status among these factors. DESIGN: Descriptive, cross
      sectional baseline data. SETTING: One urban area and 4 rural AI reservations
      nationwide. PARTICIPANTS: A total of 450 AI families with children aged 2-5years
      participating in the Healthy Children, Strong Families 2 intervention.
      INTERVENTION: Baseline data from a healthy lifestyles intervention. MAIN OUTCOME
      MEASURES: Child body mass index (BMI) z-score and adult BMI, and multiple healthy
      lifestyle outcomes. ANALYSIS: Descriptive statistics and stepwise regression.
      RESULTS: Adult and child combined overweight and obesity rates were high: 82% and
      40%, respectively. Food insecurity was high (61%). Multiple lifestyle behaviors,
      including fruit and vegetable and sugar-sweetened beverage consumption, adult
      physical activity, and child screen time, did not meet national recommendations.
      Adult sleep was adequate but children had low overnight sleep duration of 10h/d.
      Significant predictors of child obesity included more adults in the household (P
      = .003; beta = 0.153), an adult AI caregiver (P = .02; beta = 0.116), high adult
      BMI (P = .001; beta = 0.176), gestational diabetes, high child birth weight (P <
      .001; beta = 0.247), and the family activity and nutrition score (P = .04; beta =
      0.130). CONCLUSIONS AND IMPLICATIONS: We found multiple child-, adult-, and
      household-level factors influence early childhood obesity in AI children,
      highlighting the need for interventions to mitigate the modifiable factors
      identified in this study, including early life influences, home environments, and
      health behaviors.

PMID- 30241709
TI  - Neurosurgical Device-Related Infections.
AB  - In this review article, we discuss the epidemiology, microbiology, diagnosis,
      treatment and prevention of infections associated with cerebrospinal fluid
      shunts, cerebrospinal fluid drains, and deep brain stimulators. We also briefly
      discuss prevention strategies with appropriate antibiotics, devices, and
      operating room practices to decrease the risk of these infections.

PMID- 30241710
TI  - Ventricular Assist Device-Associated Infection.
AB  - Heart transplant remain the definitive therapy for end-stage heart failure but is
      limited by the availability of suitable donors. Ventricular assist devices (VAD)
      are designed as mechanical pumps to supplement or replace the function of damaged
      ventricles and maintain appropriate blood flow in patients with end-stage heart
      failure. Survival rates continue to increase in patient with VAD but infection
      remains a major cause of morbidity and mortality in VAD patients. The authors
      describe the current concepts regarding definitions, diagnosis, microbiology and
      principles of management in VAD-associated infections. The authors have also
      summarised the prevention strategies for infections in VAD patients.

PMID- 30241711
TI  - Cardiovascular Implantable Electronic Device Infections.
AB  - Infections associated with cardiac implantable electronic devices are increasing
      and are associated with significant morbidity and mortality. This article reviews
      the epidemiology, microbiology, and risk factors for acquisition of these
      infections. The complex diagnostic and management strategies associated with
      these serious infections are reviewed with an emphasis on recent updates and
      advances, as well as existing controversies. Additionally, the latest in
      preventative strategies are reviewed.

PMID- 30241712
TI  - Urinary Catheter-Associated Infections.
AB  - Catheter-associated urinary tract infection remains one of the most prevalent,
      yet preventable, health care-associated infections. General prevention strategies
      include strict adherence to hand hygiene and antimicrobial stewardship. Duration
      of urinary catheterization is the most important modifiable risk factor. Targeted
      prevention strategies include limiting urinary catheter use; physician reminder
      systems, nurse-initiated discontinuation protocols, and automatic stop orders
      have successfully decreased catheter duration. Alternatives should be considered.
      If catheterization is necessary, proper aseptic practices for insertion and
      maintenance and closed catheter collection systems are essential for prevention.
      The use of bladder bundles and collaboratives aids in the effective
      implementation of prevention measures.

PMID- 30241713
TI  - New Developments in the Prevention of Gastrointestinal Scope-Related Infections.
AB  - Gastrointestinal endoscopes are used for diagnostic and therapeutic purposes and
      are the most common medical device implicated in health care-associated
      outbreaks. Infections can be divided into endogenous or exogenous. Exogenous
      infections were associated with lapses in reprocessing. Recent outbreaks have
      occurred despite compliance with reprocessing guidelines and highlight the
      challenges with clearance of all organisms from the duodenoscopes and the
      potential role of biofilms in hindering adequate reprocessing. This review
      provides an overview of recent developments and the current understanding of the
      key contributing factors related to gastrointestinal endoscope-related infections
      and current approaches to identify and prevent these complications.

PMID- 30241714
TI  - Breast Implant Infections: An Update.
AB  - Prosthetic breast implantation is a common surgical procedure for augmentation
      and reconstruction after mastectomy. The incidence of implant infection is 1% to
      2.5% and is higher for reconstruction following mastectomy compared with
      augmentation. Most infections are caused by gram-positive pathogens, such as
      coagulase-negative staphylococci, Cutibacterium species, Staphylococcus aureus,
      and streptococci. Acute infections are usually associated with fever and breast
      pain, erythema, and drainage. Subacute infections may present with chronic pain,
      persistent drainage, failed healing of the incision site, or migration of the
      implant. Depending on severity of infection, patients are started on empiric
      intravenous or oral antibiotics and closely monitored.

PMID- 30241716
TI  - Vascular Graft Infections: An update.
AB  - Vascular graft infection is a devastating complication of vascular reconstructive
      surgery. The infection can occur early in the postoperative period and is largely
      due to intraoperative contamination or by contiguous extension from a nearby
      infection. It can also occur years after implantation. Staphylococci remain the
      most common organisms and biofilm production makes eradication difficult. Factors
      commonly reported to predispose to vascular graft infection are periodontal
      disease, nasal colonization with Staphylococcus aureus, bacteremia, certain graft
      characteristics, diabetes mellitus, postoperative hyperglycemia, location of the
      incision, wound infection, and emergency procedure. Management consists of
      antibiotic and surgical therapy. Preventive methods are described.

PMID- 30241717
TI  - Prosthetic Joint Infection Update.
AB  - Prosthetic joint infection occurs in a minority of arthroplasties performed;
      however, it brings a large burden to both the individual and society in terms of
      morbidity, mortality, and health care expenditure. Although prevention of
      prosthetic joint infection is becoming more effective, the number of total
      arthroplasties in patients with increasing comorbidities continues to rise, and
      the total number of diagnosed and managed prosthetic joint infections is expected
      to rise accordingly. Management is complex and involves a multispecialty
      approach.

PMID- 30241718
TI  - Intravascular Catheter-Related Bloodstream Infections.
AB  - Despite recent gains, intravascular catheter-related bloodstream infection
      (CRBSI) remains an important clinical problem resulting in significant morbidity,
      mortality, and excess economic cost. Successful prevention of CRBSI requires
      careful attention to insertion and maintenance protocols as well as judicious
      application of innovative technologic advancements. Appropriate treatment of
      CRBSI depends on a well-considered diagnosis, correct antimicrobial choice,
      removal of the offending device in many circumstances, and careful patient
      selection and application of antimicrobial lock therapy in patients in whom
      catheter salvage is attempted.

PMID- 30241715
TI  - Understanding Biofilms and Novel Approaches to the Diagnosis, Prevention, and
      Treatment of Medical Device-Associated Infections.
AB  - Treatment of medical device-related infections is challenging and recurrence is
      common. The main reason for this is that microorganisms adhere to the surfaces of
      medical devices and enter into a biofilm state in which they display distinct
      growth rates, structural features, and protection from antimicrobial agents and
      host immune mechanisms compared with their planktonic counterparts. This article
      reviews how microorganisms form biofilms and the mechanisms of protection against
      antimicrobial agents and the host immune system provided by biofilms. Also
      discussed are innovative strategies for the diagnosis of biofilm-associated
      infection and novel approaches to treatment and prevention of medical device
      associated infections.

PMID- 30241719
TI  - Acute-onset postoperative endophthalmitis after cataract surgery and transzonular
      intravitreal triamcinolone-moxifloxacin.
AB  - PURPOSE: To report 4 cases of acute postoperative endophthalmitis (POE) after
      uneventful temporal clear corneal topical dropless cataract surgery involving
      intravitreal triamcinolone-moxifloxacin (TriMoxi). SETTING: Private practice in
      Peoria, IL, USA. DESIGN: Retrospective noncomparative case series. METHODS:
      Charts of patients presenting with POE after an uneventful temporal clear corneal
      phacoemulsification with in-the-bag implantation of a posterior chamber
      intraocular lens over a 15-month period were reviewed. RESULTS: Patients
      presented with typical signs and symptoms of acute POE 3 to 14 days after
      cataract surgery. The POE resolved after 25-gauge pars plana vitrectomy and
      injection of intravitreal vancomycin, ceftazidime, and dexamethasone. Two of 4
      eyes were culture-positive for coagulase-negative Staphylococcus. The corrected
      distance visual acuity at the last follow-up visit was 20/40 or better in 3 eyes,
      and 20/400 in 1 eye because of underlying atrophic age-related macular
      degeneration. CONCLUSION: Postoperative endophthalmitis can occur after dropless
      cataract surgery with intravitreal triamcinolone-moxifloxacin.

PMID- 30241720
TI  - Can preoperative anterior segment optical coherence tomography predict posterior
      capsule rupture during phacoemulsification in patients with posterior polar
      cataract?
AB  - PURPOSE: To determine whether preoperative assessment of posterior capsule
      integrity using anterior segment optical coherence tomography (AS-OCT) can
      predict posterior capsule dehiscence in patients with posterior polar cataract
      having phacoemulsification. SETTING: Aravind Eye Hospital and Postgraduate
      Institute of Ophthalmology, Pondicherry, India. DESIGN: Prospective observational
      study. METHODS: Patients with posterior polar cataract who had
      phacoemulsification between October 2012 and November 2013 were included in the
      study. Preoperative AS-OCT imaging was performed to assess the integrity of the
      posterior capsule. Anterior segment OCT images of the posterior capsule were
      graded as "intact" or "dehiscent." Phacoemulsification was performed by the same
      surgeon who was masked from the AS-OCT findings. The integrity of the posterior
      capsule was evaluated by the surgeon intraoperatively. RESULTS: The study
      comprised 64 eyes of 62 patients. Preoperative AS-OCT showed 8 eyes (12.5%) to
      have probable posterior capsule dehiscence and 56 eyes (87.5%) to have intact
      posterior capsules. Intraoperatively, the surgeon noted posterior capsule
      dehiscence in 5 eyes (7.8%) and an intact posterior capsule in 59 eyes (92.2%).
      The sensitivity and specificity of AS-OCT for detecting posterior capsule
      dehiscence was 100% and 94.92%, respectively. The negative predictive value of AS
      OCT was 100%. CONCLUSION: Anterior segment OCT with its high negative predictive
      value can be used successfully to predict the risk for posterior capsule rupture
      during phacoemulsification in eyes with posterior polar cataract.

PMID- 30241721
TI  - Minority Stress Factors Associated With Depression and Anxiety Among Transgender
      and Gender-Nonconforming Youth.
AB  - PURPOSE: Transgender and gender-nonconforming (TGNC) adolescents and young adults
      experience mental health problems, including anxiety and depression, at an
      elevated rate as compared to their cisgender counterparts. A growing literature
      suggests that vulnerability to psychiatric problems in TGNC individuals results
      from social discrimination and minority stress. METHODS: The sample consisted of
      adolescent TGNC patients (N = 109) who completed behavior health screening
      questionnaires as standard of care at their first clinical visit to an
      interdisciplinary gender program within a pediatric academic medical center in a
      metropolitan Midwestern city. Binary logistic regressions were used to assess
      whether the likelihood that participants met clinical diagnostic criteria for
      Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) was
      predicted by gender identity appearance congruence, proximal forms of minority
      stress (e.g., negative expectations of the future related to gender identity;
      internalized transphobia) and community connectedness (i.e., resilience) .
      RESULTS: Overall, 33% (n = 36) of the sample met diagnostic criteria for MDD and
      48% (n = 53) met diagnostic criteria for GAD. Those with high levels of
      internalized transphobia were significantly more likely to meet diagnostic
      criteria for both MDD and GAD. Those with low levels of gender identity
      appearance congruence were significantly more likely to meet diagnostic criteria
      for MDD but not GAD. CONCLUSION: There are several unique factors that may
      predict mental illness among TGNC youth. Understanding these factors may offer
      opportunities for targeted clinical and structural interventions.

PMID- 30241722
TI  - Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in
      children with bronchiectasis (BEST-2): a multicentre, double-blind, non
      inferiority, randomised controlled trial.
AB  - BACKGROUND: Although amoxicillin-clavulanate is the recommended first-line
      empirical oral antibiotic treatment for non-severe exacerbations in children with
      bronchiectasis, azithromycin is also often prescribed for its convenient once
      daily dosing. No randomised controlled trials involving acute exacerbations in
      children with bronchiectasis have been published to our knowledge. We
      hypothesised that azithromycin is non-inferior to amoxicillin-clavulanate for
      resolving exacerbations in children with bronchiectasis. METHODS: We did this
      parallel-group, double-dummy, double-blind, non-inferiority randomised controlled
      trial in three Australian and one New Zealand hospital between April, 2012, and
      August, 2016. We enrolled children aged 1-19 years with radiographically proven
      bronchiectasis unrelated to cystic fibrosis. At the start of an exacerbation,
      children were randomly assigned to oral suspensions of either amoxicillin
      clavulanate (22.5 mg/kg, twice daily) and placebo or azithromycin (5 mg/kg per
      day) and placebo for 21 days. We used permuted block randomisation (stratified by
      age, site, and cause) with concealed allocation. The primary outcome was
      resolution of exacerbation (defined as a return to baseline) by 21 days in the
      per-protocol population, with a non-inferiority margin of -20%. We assessed
      several secondary outcomes including duration of exacerbation, time to next
      exacerbation, laboratory, respiratory, and quality-of-life measurements, and
      microbiology. This trial was registered with the Australian/New Zealand Registry
      (ACTRN12612000010897). FINDINGS: We screened 604 children and enrolled 236. 179
      children had an exacerbation and were assigned to treatment: 97 to amoxicillin
      clavulanate, 82 to azithromycin). By day 21, 61 (84%) of 73 exacerbations had
      resolved in the azithromycin group versus 73 (84%) of 87 in the amoxicillin
      clavulanate group. The risk difference showed non-inferiority (-0.3%, 95% CI 
      11.8 to 11.1). Exacerbations were significantly shorter in the amoxicillin
      clavulanate group than in the azithromycin group (median 10 days [IQR 6-15] vs 14
      days [8-16]; p=0.014). Adverse events were attributed to the trial medication in
      17 (21%) of 82 children in the azithromycin group versus 23 (24%) of 97 in the
      amoxicillin-clavulanate group (relative risk 0.9, 95% CI 0.5 to 1.5).
      INTERPRETATION: By 21 days of treatment, azithromycin is non-inferior to
      amoxicillin-clavulanate for resolving exacerbations in children with non-severe
      bronchiectasis. In some patients, such as those with penicillin hypersensitivity
      or those likely to have poor adherence, azithromycin provides another option for
      treating exacerbations, but must be balanced with risk of treatment failure
      (within a 20% margin), longer exacerbation duration, and the risk of inducing
      macrolide resistance. FUNDING: Australian National Health and Medical Research
      Council.

PMID- 30241724
TI  - New surgical method of tongue reduction for macroglossia: technical note.
AB  - OBJECTIVE: We describe here a new surgical technique, which allows for efficient
      tongue reduction with satisfactory appearance and avoids the complications of tip
      excision. STUDY DESIGN: This is a retrospective case review that includes 6
      patients who had macroglossia and underwent tongue reduction using our new
      central V-shaped excision technique. Three patients were operated on at an early
      age because of significant macroglossia with permanent tongue protrusion,
      cosmetic disorder, and speech delay. The other 3 patients underwent surgery
      performed in their teenage years because medical treatment had been unsuccessful.
      We assessed tongue shape, mobility, taste, and sensitivity. RESULTS: The
      postoperative follow-up period ranged from 2 months to 16years (average 7 years).
      On subjective evaluation, all patients were satisfied with the appearance of the
      tongue and reported no sensitive or sensory difficulties. The patients reported
      normal food progression in the oral cavity. Objective evaluation showed that the
      tongue had normal mobility, taste, and sensitivity. Postoperatively, there was no
      residual tongue protrusion, cosmetic disorder, or speech delay. None of the
      patients needed revision surgery. CONCLUSIONS: This central V-shaped excision
      offers good surgical results, with efficient tongue reduction and none of the
      complications of other tongue reduction techniques, such as tip amputation or
      anterior wedge resection.

PMID- 30241723
TI  - Treatment of bronchiectasis exacerbations in children: which antibiotic?

PMID- 30241725
TI  - Cardiac chronotropic hypo-responsiveness and atrial fibrosis in rats chronically
      treated with lithium.
AB  - Lithium is a widely used mood-stabilizing agent; however, it causes a variety of
      cardiovascular side effects including sinus node dysfunction. In this study we
      explored the potential adverse effects of lithium on cardiac chronotropic
      responsiveness, atrial tissue histology and gene expression in rats that were
      chronically treated with therapeutic doses of lithium. Male Wistar albino rats
      were given lithium chloride (2.5 g/kg) orally for 2 or 3 months. Following
      treatment, the atria were isolated and spontaneously beating rate and
      chronotropic responsiveness to beta-adrenergic stimulation was evaluated in an
      organ bath. Development of cardiac fibrosis was examined by histological methods.
      The expression of atrial Col1a1 (collagen I, alpha 1) and beta-arrestin2 was also
      assessed using quantitative RT-PCR. Treatment with lithium induced a significant
      hypo-responsiveness to adrenergic stimulation (P < 0.001) and caused fibrosis in
      the atrial tissue of treated rats. In addition, the expression of atrial Col1a1
      mRNA was significantly increased in atrial tissues of lithium-treated animals,
      while beta-arrestin2 mRNA expression did not show a significant difference
      compared with control animals. Altogether, these findings indicate that cardiac
      chronotropic hypo responsiveness and associated cardiac fibrosis are side effects
      of chronic lithium treatment. Moreover, it seems that lithium treatment does not
      influence beta-arrestin2 mRNA expression.

PMID- 30241726
TI  - Response to: INTER-SCAN REPRODUCIBILITY OF CAROTID PLAQUE VOLUME MEASUREMENTS BY
      3-D ULTRASOUND; Methodological issues to avoid misinterpretation.

PMID- 30241727
TI  - Experimental Investigation of Guided Wave Imaging in Thin Soft Media under
      Various Coupling Conditions.
AB  - Guided wave imaging for the artery remains in its infancy in clinical practice
      mainly because of complex arterial microstructure, hemodynamics and boundary
      conditions. Despite the theoretically known potential effect of the surrounding
      medium on guided wave propagation in thin media in non-destructive testing,
      experimental evidence pertaining to thin soft materials, such as the artery, is
      relatively scarce in the relevant literature. Therefore, this study first
      evaluated the propagating guided wave generated by acoustic radiation force in
      polyvinyl alcohol-based hydrogel plates differing in thickness and stiffness
      under various material coupling conditions (water and polyvinyl alcohol bulk). A
      thin-walled polyvinyl alcohol hollow cylindrical phantom coupled by softer
      gelatin-agar phantoms and an excised porcine aorta surrounded by water and pork
      belly were further examined. Guided waves in the thin structure and shear waves
      in the bulk media were captured by ultrafast ultrasound imaging, and guided wave
      dispersion as a function of the frequency-thickness product was analyzed using
      the zero-order anti-symmetric Lamb wave model to estimate the shear modulus of
      each thin medium studied. Results confirmed the deviated shear modulus estimates
      from the ground truth for thin plates, the thin-walled hollow cylindrical phantom
      and the porcine aorta bounded by stiffness-unmatched bulk medium. The findings
      indicated the need for (i) careful interpretation of estimated shear moduli of
      thin structure bounded by bulk media and (ii) a generalized guided wave model
      that takes into account the effect of coupling medium.

PMID- 30241728
TI  - Point Shear Wave Elastography for Non-invasive Assessment of Liver Fibrosis in
      Patients with Viral Hepatitis.
AB  - Elastography point quantification (ElastPQ) is a new ultrasound-based shear wave
      elastography method for non-invasive assessment of liver fibrosis. We evaluated
      the diagnostic accuracy of ElastPQ in patients with chronic viral hepatitis.
      Fibrosis stage (F) was determined by transient elastography (F0/F1: <7.1 kPa, F2:
      7.1-9.4 kPa, F3: 9.5-12.4 kPa, F4: >=12.5 kPa). Area under the receiver operator
      characteristics curve (AUROC) analysis was performed to assess ElastPQ cutoffs
      for significant fibrosis (>=F2) and cirrhosis (F4). Paired transient elastography
      and ElastPQ measurements were obtained from 217 patients (mean age +/- SEM: 49 +/
      0.79 years, 68.2% male, F0/F1: n = 98 [45.0%], F2: 47 [21.6%], F3: 22 [10.1%],
      F4: 50 [22.9%]). AUROC for >=F2 was 0.843 (95% confidence interval: 0.791-0.895),
      and for F4, 0.933 (95% confidence interval: 0.894-0.972). The optimal ElastPQ
      cutoff for F2 was 6.68 kPa (sensitivity: 80.7%, specificity: 70.4%, positive
      predictive value: 78.5%, negative predictive value: 72.3%), and for F4 11.28 kPa
      (sensitivity: 86.0%, specificity: 85.6%, positive predictive value: 60.52%,
      negative predictive value: 97.16%). In conclusion, ElastPQ represents an accurate
      tool for non-invasive staging of liver fibrosis in patients with viral hepatitis.

PMID- 30241729
TI  - Engineering Theranostic Microbubbles Using Microfluidics for Ultrasound Imaging
      and Therapy: A Review.
AB  - Microbubbles interact with ultrasound in various ways to enable their
      applications in ultrasound imaging and diagnosis. To generate high contrast and
      maximize therapeutic efficacy, microbubbles of high uniformity are required.
      Microfluidic technology, which enables precise control of small volumes of fluid
      at the sub-millimeter scale, has provided a versatile platform on which to
      produce highly uniform microbubbles for potential applications in ultrasound
      imaging and diagnosis. Here, we describe fundamental microfluidic principles and
      the most common types of microfluidic devices used to produce sub-10 MUm
      microbubbles, appropriate for biomedical ultrasound. Bubbles can be engineered
      for specific applications by tailoring the bubble size, inner gas and shell
      composition and by functionalizing for additional imaging modalities,
      therapeutics or targeting ligands. To translate the laboratory-scale discoveries
      to widespread clinical use of these microfluidic-based microbubbles, increased
      bubble production is needed. We present various strategies recently developed to
      improve scale-up. We conclude this review by describing some outstanding problems
      in the field and presenting areas for future use of microfluidics in ultrasound.

PMID- 30241730
TI  - Full-scale composting of sewage sludge and market waste: Stability monitoring and
      odor dispersion modeling.
AB  - The aim of this study was to assess the odor immission derived from full-scale
      composting of different abundant and highly pollutant organic waste: sewage
      sludge with bulking agent (SL), sewage sludge pretreated through anaerobic
      digestion and supplemented with bulking agent (SL-AD), and market waste with
      olive leaves (MW-OL). The combination of dynamic olfactometry and Gaussian
      dispersion modeling allowed both the quantification of odor emissions from each
      waste and the evaluation of their global odorous impact in nearby urban areas.
      Wind speed, summer and winter seasons, and atmospheric conditions were considered
      in the dispersion model. The results revealed that high wind speed (2.6 m/s)
      increases the global odor immission in summer season, independently of
      atmospheric stability. However, the maximum odor immission concentration
      recommended for composting process was not exceeded in any case, which depends on
      each country/region. The experimental results also enable to evaluate the
      influence of several physico-chemical variables on odor emissions derived from
      composting. The removal of nitrogen and volatile solids was the main cause for
      odor generation. Moreover, the microbiological activity of each substrate was
      monitored throughout the process and different percentages of biodegradability
      were quantified depending on the type of substrate and pretreatment applied.

PMID- 30241731
TI  - Association between floods and typhoid fever in Yongzhou, China: Effects and
      vulnerable groups.
AB  - BACKGROUND: Little information about the effects of floods on typhoid fever is
      available in previous studies. This study aimed to examine the relationships
      between floods and typhoid fever and to identify the vulnerable groups in
      Yongzhou, China. METHODS: Weekly typhoid fever data, flood data and
      meteorological data during the flood season (April to September) from 2005 to
      2012 were collected for this study. A Poisson generalized linear model combined
      with a distributed lag non-linear model was conducted to quantify the lagged and
      cumulative effects of floods on typhoid fever, considering the confounding
      effects of long-term trend, seasonality, and meteorological variables. The model
      was also used to calculate risk ratios of floods for weekly typhoid fever cases
      among various subpopulations. RESULTS: After adjusting for long-term trend,
      seasonality, and meteorological variables, floods were associated with an
      increased number of typhoid fever cases with a risk ratio of 1.46 (95% CI: 1.10
      1.92) at 1-week lag and a cumulative risk ratio of 1.76 (95% CI: 1.21-2.57) at
      lag 0-1 weeks. Males, people aged 0-4 years old, people aged 15-64 years old,
      farmers, and children appeared to be more vulnerable than the others.
      CONCLUSIONS: Our study indicates that floods could significantly increase the
      risks of typhoid fever with lag effects of 1 week in the study areas.
      Precautionary measures should be taken with a focus on the identified vulnerable
      groups in order to control the transmission of typhoid fever associated with
      floods.

PMID- 30241732
TI  - Oligogenic familial hypercholesterolemia, LDL cholesterol, and coronary artery
      disease.
AB  - BACKGROUND: The genetic background of severe familial hypercholesterolemia (FH)
      has yet to be determined. OBJECTIVE: We tested if genetic variants associated
      with low-density lipoprotein (LDL)-altering autosomal recessive diseases
      influenced LDL cholesterol levels and the odds for coronary artery disease in
      patients with high LDL cholesterol. METHODS: We recruited 500 individuals with
      elevated LDL cholesterol levels (>=180 mg/dL or >=140 mg/dL for subjects <15
      years). We sequenced the exons of 3 FH genes (LDLR, apolipoprotein B, and
      proprotein convertase subtilisin/kexin type 9) and 4 LDL-altering accessory genes
      (ABCG5, ABCG8, APOE, and LDL receptor adaptor protein 1). In addition, 4 single
      nucleotide polymorphisms associated with polygenic FH in East Asian subjects were
      genotyped. Oligogenic FH patients were defined as those who harbored damaging
      variants of both conventional FH genes and LDL-altering accessory genes. RESULTS:
      We identified damaging variants of conventional FH genes in 248 participants
      (50%). We also detected damaging variants in accessory genes in 57 patients (11%)
      and identified oligogenic FH in 27 of these patients (5%). Polygenic score in the
      subjects without any FH mutations was significantly higher than those in any
      other groups. Compared with monogenic FH, oligogenic FH exhibited significantly
      higher LDL cholesterol (265 mg/dL, 95% confidence interval [CI] 216-312, and 210
      mg/dL, 95% CI 189-243; P = .04). Oligogenic FH exhibited higher odds for coronary
      artery disease when compared with monogenic FH, although it did not reach
      statistical significance (odds ratio 1.41, 95% CI 0.68-2.21, P = .24).
      CONCLUSIONS: Among patients with elevated LDL cholesterol, those with oligogenic
      FH had higher LDL cholesterol than monogenic FH.

PMID- 30241733
TI  - A biomechanical cadaver comparison of suture button fixation to plate fixation
      for pubic symphysis diastasis.
AB  - OBJECTIVES: To determine whether suture button fixation of the pubic symphysis is
      biomechanically similar to plate fixation in the treatment of partially stable
      pelvic ring injuries. METHODS: Twelve pelvis specimens were harvested from fresh
      frozen cadavers. Dual-x-ray-absorptiometry (DXA) scans were obtained for all
      specimens. The pubic symphysis of each specimen was sectioned to simulate a
      partially stable pelvic ring injury. Six of the pelvises were instrumented using
      a 6 hole, 3.5 mm low profile pelvis plate and six of the pelvises were
      instrumented with two suture button devices. Biomechanical testing was performed
      on a pneumatic testing apparatus in a manner that simulates vertical stance.
      Displacement measurements of the superior, middle, and inferior pubic symphysis
      were obtained prior to loading, after an initial 440 N load, and after 30,000 and
      60,000 rounds of cyclic loading. Statistical analysis was performed using
      Wilcoxon-Mann-Whitney tests, Fisher's exact test, and Cohen's d to calculate
      effect size. Significance was set at p < 0.05. RESULTS: There was no difference
      between groups for DXA T scores (p = 0.749). Between group differences in
      clinical load to failure (p = 0.65) and ultimate load to failure (p = 0.52) were
      not statistically significant. For symphysis displacement, the change in fixation
      strength and displacement with progressive cyclic loading was not significant
      when comparing fixation types (superior: p = 0.174; middle: p = 0.382; inferior:
      p = 0.120). CONCLUSION: Suture button fixation of the pubic symphysis is
      biomechanically similar to plate fixation in the management of partially stable
      pelvic ring injuries.

PMID- 30241734
TI  - Pathogens Suppress Host Transcription Factors for Rampant Proliferation.
AB  - Root pathogen Verticillium dahliae deploys an effector called VdSCP41 into plants
      to disrupt the functions of SARD1 and CBP60g, two central transcriptional
      regulators of plant immunity. This provides new tools to dissect transcriptional
      regulation of tissue-specific immunity in the root and to understand dynamic
      interactions between plants and root-associated microorganisms.

PMID- 30241735
TI  - Crop Gene-Editing: Should We Bypass or Apply Existing GMO Policy?
AB  - Recent advances in crop gene-editing technologies allow for efficient site
      specific mutagenesis without introducing exogenous DNA, potentially bypassing
      product-based genetically modified organism (GMO) regulations. Conversely, such
      plants can be subject to process-based GMO regulations. However, it is important
      to tailor existing GMO regulations with the aim to ensure social acceptance of
      gene-edited crops.

PMID- 30241736
TI  - Growing Research Networks on Mycorrhizae for Mutual Benefits.
AB  - Research on mycorrhizal interactions has traditionally developed into separate
      disciplines addressing different organizational levels. This separation has led
      to an incomplete understanding of mycorrhizal functioning. Integration of
      mycorrhiza research at different scales is needed to understand the mechanisms
      underlying the context dependency of mycorrhizal associations, and to use
      mycorrhizae for solving environmental issues. Here, we provide a road map for the
      integration of mycorrhiza research into a unique framework that spans genes to
      ecosystems. Using two key topics, we identify parallels in mycorrhiza research at
      different organizational levels. Based on two current projects, we show how
      scientific integration creates synergies, and discuss future directions. Only by
      overcoming disciplinary boundaries, we will achieve a more comprehensive
      understanding of the functioning of mycorrhizal associations.

PMID- 30241737
TI  - [CO2 LASER for the treatment of vaginal symptoms of genitourinary syndrome of
      menopause].
AB  - Genitourinary syndrome of menopause (GSM) brings together a collection of signs
      including vaginal dryness, burning sensation and itching discomfort as well as
      deterioration of sexual health, dysuria, urgenturia and repeated urinary
      infections and may be responsible for a significant impairment of quality of life
      in symptomatic postmenopausal women. The management of GSM therefore represents a
      public health issue. Systemic or local hormonal treatments are frequently
      offered, as well as non-hormonal treatments. The existence of contraindications
      to hormonal treatments and the constraints of using local treatments lead us to
      propose other therapeutic options. CO2 LASER is now part of the therapeutic
      arsenal for the treatment of vaginal dryness in the context of GSM. There is a
      growing interest in this technique, especially for women who have a
      contraindication to hormonal therapy, as it is a globally effective, long-acting
      alternative with very little adverse effect. Current evidence suggests that this
      tool could provide a quality of life benefit to many patients with minimal side
      effect exposure, if used in the respect of its indications and implementation
      protocols. However, clinical data based on high-level therapeutic trials remain
      absolutely essential for this treatment to be validated and recommended by health
      professionals.

PMID- 30241738
TI  - ?

PMID- 30241739
TI  - Bone grafting in orthognathic surgery: a systematic review.
AB  - Bone grafting has been used in orthognathic surgery to fill the gaps created by
      jaw repositioning, with the intention of improving healing and stability. Since
      the majority of orthognathic cases have a satisfactory result, the decision to
      graft or not is a clinical dilemma. A systematic review of the literature was
      performed on the use of bone grafts in orthognathic surgery. A search of PubMed,
      MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials yielded
      1927 articles published up until 2018. An additional 10 articles were retrieved
      through manual searching of the reference lists and citations. After title and
      abstract screening, 58 articles were potentially eligible; full-text screening
      excluded 10 of these. Thus 48 articles were included in this review. The present
      literature highlights the benefits of grafting bony gaps during orthognathic
      surgery in terms of healing, stability, and aesthetic outcomes. Generally, there
      was no difference between the various types of bone graft, although calcium
      phosphate cement and hydroxyapatite were found to increase the rate of infection.
      The conclusion of this review is that there remains a lack of evidence in the
      literature regarding the grafting of osteotomy sites in orthognathic surgery.
      Guidelines are proposed based on the present evidence; however, future research
      is needed to validate these.

PMID- 30241740
TI  - Risk factors and prognosis for the primary intraosseous carcinoma of the jaw.
AB  - Primary intraosseous carcinoma (PIOC) is a rare but aggressive type of
      odontogenic tumour arising within the jawbone. Diagnosis criteria and treatment
      strategy remain difficult and controversial. The present study aimed to clarify
      the clinicopathological features and determine prognostic factors in management
      of PIOC. A retrospective study of 30 patients with PIOC, treated at the Hospital
      of Stomatology of Sun Yat-sen University between 2009 and 2017, was conducted.
      Clinical, histopathological and treatment modality data were collected. Follow-up
      data were recorded to determine prognostic factors. There were 19 males and 11
      females with a mean age of 52.3 years. The most common location of the tumour was
      the mandible (90%). Having a history of tooth extraction or tooth mobility was
      the major characteristic symptom (63.3%), jaw swelling coming in second (53.3%).
      Half of the patients underwent surgery alone. The estimated 2-year overall
      survival rate (OS) and recurrence-free survival rate (RFS) were 61.3% and 40.1%,
      respectively. Higher histological grade was an independent risk factor for poor
      OS (hazard ratio (HR) 0.233 [0.059-0.915], P=0.037), while at pN+ stage for RFS,
      HR=5.627 [1.199-26.409], P=0.029. Because of its rarity and intrabony site, the
      classification, staging and treatment guidelines for PIOC should be further
      studied and established.

PMID- 30241741
TI  - AAV Immunogenicity: A Matter of Sensitivity.

PMID- 30241743
TI  - A proposed enhancement to the in air sensitivity test for ultrasound quality
      assurance.
AB  - PURPOSE: A number of guidelines for ultrasound quality assurance recommend the
      use of the in air reverberation depth as a proxy measure for sensitivity. The
      test is quantised, i.e. it depends on the brightness of the deepest in air
      reverberation. The aim of this study was to investigate a possible enhancement to
      the test, where the gain is reduced to determine the "reverberation threshold".
      METHODS: The test was introduced in several ultrasound departments. Results were
      audited to determine agreement with annual tests of sensitivity using a tissue
      mimicking test object. RESULTS: The new test was performed on 100 probes. A
      change in reverberation threshold was demonstrated in 9 probes; 8 of these also
      had changes in penetration and/or grey level in a tissue mimicking test object.
      Reduced penetration but no change in reverberation threshold was seen in 2
      probes. CONCLUSIONS: The reverberation threshold provides a simple enhancement to
      the in air sensitivity test. Periodic sensitivity testing with a tissue mimicking
      test object remains important.

PMID- 30241742
TI  - Nanoparticles Based on Poly (beta-Amino Ester) and HPV16-Targeting CRISPR/shRNA
      as Potential Drugs for HPV16-Related Cervical Malignancy.
AB  - Persistent high-risk HPV infection is the main cause of cervical cancer. The HPV
      oncogene E7 plays an important role in HPV carcinogenesis. Currently, HPV
      vaccines do not offer an effective treatment for women who already present with
      cervical disease, and recommended periodical cervical screenings are difficult to
      perform in countries and areas lacking medical resources. Our aim was to develop
      nanoparticles (NPs) based on poly (beta-amino ester) (PBAE) and HPV16 E7
      targeting CRISPR/short hairpin RNA (shRNA) to reduce the levels of HPV16 E7 as a
      preliminary form of a drug to treat HPV infection and its related cervical
      malignancy. Our NPs showed low toxicity in cells and mouse organs. By reducing
      the expression of HPV16 E7, our NPs could inhibit the growth of cervical cancer
      cells and xenograft tumors in nude mice, and they could reverse the malignant
      cervical epithelium phenotype in HPV16 transgenic mice. The performance of NPs
      containing shRNA is better than that of NPs containing CRISPR. HPV-targeting NPs
      consisting of PBAE and CRISPR/shRNA could potentially be developed as drugs to
      treat HPV infection and HPV-related cervical malignancy.

PMID- 30241744
TI  - Patient's Peak Skin Dose evaluation using Gafchromic films in interventional
      cardiology procedures and its correlation with other dose indicators.
AB  - OBJECTIVE: Number and complexity of interventional cardiology procedures have
      increased during last years and can result in patient skin dose high enough to
      cause deterministic skin effects. The aim of the work is to investigate the
      correlation between Peak Skin Dose (PSD) and the dosimetric indicators directly
      registered by the radiological equipment and provide the physicians a tool to
      identify patients at risk of deterministic effects and include them into a follow
      up program. METHODS: PSD was measured in vivo using radiochromic Gafchromic XR
      RV3 films, properly calibrated. DAP, Cumulative Dose at the interventional
      reference point (CD) and exposure time of each procedure were retrieved from the
      Radiation Dose Structured Reports created by an Allura Clarity Xper FD20
      angiographic system. Linear correlation between PSD and both DAP and CD was
      investigated. RESULTS: 42 interventional cardiology procedures (16 CA and 26
      PTCA) were involved in the study. The dosimetric indicators values for PTCA are
      generally higher than those for CA, due to the different levels of procedure
      complexity. Mean PSD values were (103 +/- 64) and (526 +/- 436) mGy for CA and
      PTCA procedures. For CA, we found strong correlation both between PSD and DAP (r
      = 0.753) and PSD and CD (r = 0.782). For PTCA, good correlation both for DAP (r =
      0.648) and CD (r = 0.649) was found. CONCLUSIONS: DAP and CD show strong
      correlation with PSD measured with Gafchromic films during interventional
      procedures. The proposed method allows the physician to estimate patient's PSD
      from the dosimetric indicators that the radiological equipment display and record
      at the end of the procedure.

PMID- 30241745
TI  - Variations in slice sensitivity profile for various height settings in
      tomosynthesis imaging: Phantom study.
AB  - Understanding the properties of slice sensitivity profile (SSP), or slice
      thickness, is crucial for an accurate and highly reproducible diagnosis using
      tomosynthesis imaging. The objectives of the present study are therefore to
      quantitatively evaluate how the SSP with the use of a small metal bead is
      affected by different settings of the height from the table and the height of the
      center of rotation (COR) in tomosynthesis imaging except for the digital breast
      tomosynthesis, and visually verify the effects on tomosynthesis images. The
      reconstruction filters used were three types of filtered back-projection and
      iterative reconstructions. The SSP was measured from the full width at half
      maximum (FWHM-SSP) of the profile curve of the bead in the perpendicular
      direction (z direction) relative to the table. Two types of anthropomorphic
      phantoms simulating the human body, with bones and soft tissues, were used to
      study the effects of different settings for the COR height. In all reconstruction
      filters, the FWHM-SSP changed as the height of the bead varied when the bead and
      COR were set to the same height from the table. If the bead and the COR were set
      to different heights, the FWHM-SSP increased (decreased) when the height of the
      bead was set to be greater (less) than the height of the COR. These changes were
      also confirmed on the anthropomorphic phantom images of the bones and soft
      tissues.

PMID- 30241746
TI  - Impact of shoulder deformation on volumetric modulated arc therapy doses for head
      and neck cancer.
AB  - PURPOSE: When using volumetric modulated arc therapy (VMAT) for head and neck
      cancer, setup errors regarding the shoulders can create loss of target coverage
      or increased organ-at-risk doses. This study created variations of realistic
      shoulder deformations to understand the associated VMAT dosimetric effects and
      investigated water-equivalent thickness (WET) differences using in-house
      software. METHODS: Ten patients with head and neck cancer with lower neck
      involvement were retrospectively and randomly enrolled. Their retrospective
      analysis comprised treatment planning using RayStation 5.0 (RaySearch
      Laboratories, Stockholm, Sweden), shoulder deformation of 5-15 mm in three
      dimensional axes using the ImSimQA package (Oncology Systems Limited, Shrewsbury,
      Shropshire, UK), and evaluation of the clinical impact of the dose distribution
      after recalculating the dose distribution using computed tomography images of
      deformed shoulders and deforming the dose distribution. Additionally, our in
      house software program was used to measure WET differences for shoulder
      deformation. RESULTS: WET differences were greater in the superoinferior (SI)
      direction than in the other directions (the WET difference was >20 mm for 15-mm
      SI deformation). D99%, D98%, and D95% for all clinical target volumes were within
      3%. Local dose differences of more than +/-10% were found for normal tissues at
      the level of the shoulder for 15-mm movement in the SI direction. CONCLUSIONS:
      Shoulder deformation of >6 mm could cause large dose variations delivered to the
      targeted tissue at the level of the shoulder. Thus, to ensure delivery of
      appropriate treatment coverage to the targeted tissue, shoulder deformation
      should be taken into consideration during the planning stage.

PMID- 30241747
TI  - Out-of-field doses from secondary radiation produced in proton therapy and the
      associated risk of radiation-induced cancer from a brain tumor treatment.
AB  - PURPOSE: To determine out-of-field doses produced in proton pencil beam scanning
      (PBS) therapy using Monte Carlo simulations and to estimate the associated risk
      of radiation-induced second cancer from a brain tumor treatment. METHODS:
      Simulations of out-of-field absorbed doses were performed with MCNP6 and
      benchmarked against measurements with tissue-equivalent proportional counters
      (TEPC) for three irradiation setups: two irradiations of a water phantom using
      proton energies of 78-147 MeV and 177-223 MeV, and one brain tumor irradiation of
      a whole-body phantom. Out-of-field absorbed and equivalent doses to organs in a
      whole-body phantom following a brain tumor treatment were subsequently simulated
      and used to estimate the risk of radiation-induced cancer. Additionally, the
      contribution of absorbed dose originating from radiation produced in the nozzle
      was calculated from simulations. RESULTS: Out-of-field absorbed doses to the TEPC
      ranged from 0.4 to 135 uGy/Gy. The average deviation between simulations and
      measurements of the water phantom irradiations was about 17%. The absorbed dose
      contribution from radiation produced in the nozzle ranged between 0 and 70% of
      the total dose; the contribution was however small in absolute terms. The
      absorbed and equivalent doses to the organs ranged between 0.2 and 60 uGy/Gy and
      0.5-151 uSv/Gy. The estimated lifetime risk of radiation-induced second cancer
      was approximately 0.01%. CONCLUSIONS: The agreement of out-of-field absorbed
      doses between measurements and simulations was good given the sources of
      uncertainties. Calculations of out-of-field organ doses following a brain tumor
      treatment indicated that proton PBS therapy of brain tumors is associated with a
      low risk of radiation-induced cancer.

PMID- 30241748
TI  - A new less toxic polymer gel dosimeter: Radiological characteristics and
      dosimetry properties.
AB  - PURPOSE: A new polymer gel dosimeter recipe was investigated that may be more
      suitable for widespread applications than polyacrylamide gel dosimeters, since
      the extremely toxic acrylamide has been replaced with the less harmful monomer 2
      Acrylamido 2-Methyl Propane Sulfonic acid (AMPS). METHODS: The new formulation
      was named PAMPSGAT. The MRI response (R2) of the dosimeters was analyzed for
      conditions of varying dose, dose rate, and temperature during scanning.
      Radiological properties of the PAMPSGAT polymer gel dosimeter were investigated.
      RESULTS: The dose-response (R2) of AMPS/Bis appears to be linear over a dose
      range 10-40 Gy. The percentage of difference between the R2 values for imaging at
      15  degrees C and MRI room temperature is about 4.6% for vial with 40 Gy absorbed
      dose which decreased to less than 1% for imaging at 20  degrees C. The percentage
      difference of Zeff of PAMPSGAT gel and soft tissue was less than 1% in the
      practical energy range (100 KeV-100 MeV). The electron density of the PAMPSGAT
      polymer gel was 2.9% higher than that of muscle. Results showed that the
      sensitivity of PAMPSGAT polymer gel dosimeter irradiated by 60Co (energy = 1.25
      MeV) is about 27.7% higher than that of irradiated using a 6 MeV Linac system.
      CONCLUSIONS: Temperature during MRI scanning has a small effect on the R2
      response of the PAMPSGAT polymer gel dosimeter. Results confirmed tissue
      equivalency of the PAMPSGAT polymer gel dosimeter in most practical energy range.
      The PAMPSGAT polymer gel dosimeter response depends on energy and dose rate.

PMID- 30241750
TI  - Investigation on the resolution of a micro cone beam CT scanner scintillating
      detector using Monte Carlo methods.
AB  - The impact of several physical quantities on the spatial resolution of an X-ray
      scintillating pixel detector for a micro cone beam CT (uCBCT) is investigated and
      discussed. The XtremeCT from SCANCO Medical AG was simulated using the
      EGSnrc/EGS++ Monte Carlo (MC) framework and extensively benchmarked in a previous
      work. The resolution of the detector was determined by simulating a titanium
      knife-edge to obtain the edge spread function (ESF) and the modulation transfer
      function (MTF). Propagation of the scintillation light through the scintillator
      and its coupling into the fiber optics system was taken into account. The
      contribution of particles scattered in the main scanner components to the
      detector signal is very low and does not affect the spatial resolution of the
      detector. The resolution obtained from the energy deposition in the scintillator
      without any blurring due to the propagation of the scintillation light into the
      fiber optics array was 31 um. By assuming isotropic light propagation in the
      scintillator, the resolution degraded to 360 um. A simple light propagation model
      taking into account the impact of the scintillator's columnar microstructures was
      developed and compared with the MANTIS Monte Carlo simulation package. By
      reducing the width of the model's light propagation kernel by a factor of 2
      compared to the isotropic case, the detector resolution can be improved to 83 um,
      which corresponds well to the measured resolution of 86 um. The resolution of the
      detector is limited mainly by the propagation of the scintillation light through
      the scintillator layer. It offers the greatest potential to improve the
      resolution of the uCBCT imaging system.

PMID- 30241749
TI  - An end-to-end postal audit test to examine the coincidence between the imaging
      isocenter and treatment beam isocenter of the IGRT linac system for Japan
      Clinical Oncology Group (JCOG) clinical trials.
AB  - PURPOSE: The aim of this study was to develop an end-to-end postal audit test to
      examine the coincidence between the imaging isocenter and treatment beam
      isocenter of the image guided radiotherapy (IGRT) linac system for Japan Clinical
      Oncology Group (JCOG) trials, as a part of IGRT credentialing of institutions
      participating in JCOG trials. METHODS: We developed an end-to-end postal audit
      test to verify radiation positional errors associated with IGRT techniques. This
      test is intended for simulating a clinical IGRT flow and uses a static cubic
      phantom measuring 15 * 15 * 15 cm3 and weighing approximately 3.4 kg. The phantom
      has four gold fiducial markers and a spherical dummy target for setup, with known
      shift values from the phantom center. Two pairs of Gafchromic RTQA2 films were
      inserted 5 mm from the phantom's anterior-posterior and right-left surfaces.
      Radiation positional errors at the isocenter were determined by analyzing the
      center of the radiation field on the films and the known shift values of the
      dummy target. The test was performed on 47 IGRT devices at 35 institutions.
      RESULTS: Radiation positional errors were within acceptance levels (1 mm/1
      degrees ) for 42 IGRT devices (89.4%) in the first check. Median time to complete
      IGRT credentialing was 11.5 days. This audit method was applicable for any
      radiotherapy machine with an IGRT device. CONCLUSIONS: A postal audit test to
      verify radiation positional errors for JCOG trials was successfully developed. In
      the postal audit, all but one institution passed this credentialing item within
      two trials.

PMID- 30241751
TI  - Comparison of multi-institutional pre-treatment verification for VMAT of
      nasopharynx with delivery errors.
AB  - PURPOSE: Measurement-based pre-treatment verification with phantoms frequently
      uses gamma analysis to assess acceptable delivery accuracy. This study evaluates
      the sensitivity of a commercial system to simulated machine errors for three
      different institutions' Volumetric Modulated Arc Therapy (VMAT) planning
      approaches. METHODS: VMAT plans were generated for ten patients at three
      institutions using each institution's own protocol (manually-planned at
      institution 1; auto-planned at institutions 2 and 3). Errors in Multi-Leaf
      Collimator (MLC) field size (FS), MLC shift (S), and collimator angle (C) of -5, 
      2, -1, 1, 2 and 5 mm or degrees were introduced. Dose metric constraints
      discriminated which error magnitudes were considered unacceptable. The smallest
      magnitude error treatment plans deemed clinically unacceptable (typically for a
      5% dose change) were delivered to the ArcCHECK for all institutions, and with a
      high-dose point ion chamber measurement in 2 institutions. Error detection for
      different gamma analysis criteria was compared. RESULTS: Not all deliberately
      introduced VMAT plan errors were detected using a typical 3D 3%/3 mm global gamma
      pass rate of 95%. Considering all institutions, gamma analysis was least
      sensitive to negative FS errors. The most sensitive was a 2%/2 mm global analysis
      for institution 1, whilst for institution 2 it was 3%/3 mm global analysis. The
      majority of errors (58/59 for institution 1, 54/60 for institution 3) were
      detected using ArcCHECK and ion chamber measurements combined. CONCLUSIONS: Not
      all clinically unacceptable errors are detected. Combining ion chamber
      measurements with gamma analysis improved sensitivity and is recommended. Optimum
      gamma settings varied across institutions.

PMID- 30241752
TI  - Tomotherapy treatment site specific planning using statistical process control.
AB  - BACKGROUND: This study investigated planned MLC distribution and treatment region
      specific plan parameters to recommend optimal delivery parameters based on
      statistical process techniques. METHODS: A cohort of 28 head and neck, 19 pelvic
      and 23 brain pre-treatment plans were delivered on a helical tomotherapy system
      using 2.5 cm field width. Parameters such as gantry period, leaf open time (LOT),
      actual modulation factor, LOT sonogram, treatment duration and couch travel were
      investigated to derive optimal range for plans that passed acceptable delivery
      quality assurance. The results were compared against vendor recommendations and
      previous publications. RESULTS: No correlation was observed between vendor
      recommended gantry period and percentage of minimum leaf open times. The range of
      gantry period (min-max) observed was 16-21 s for head and neck, 15-22 s for
      pelvis and 13-18 s for brain plans respectively. It was also noted that the
      highest percentage (average (X-) +/- SD) of leaf open times for a minimum time of
      100 ms was seen for brain plans (53.9 +/- 9.2%) compared to its corresponding
      head and neck (34.5 +/- 4.2%) and pelvic (32.0 +/- 9.4%) plans respectively.
      CONCLUSIONS: We have proposed that treatment site specific delivery parameters be
      used during planning that are based on the treatment centre and have detailed
      recommendations and limitations for the studied cohort. This may enable to
      improve efficiency of treatment deliveries by reducing inaccuracies in MLC
      distribution.

PMID- 30241753
TI  - Development of a novel algorithm for metal artifact reduction in digital
      tomosynthesis using projection-based dual-energy material decomposition for
      arthroplasty: A phantom study.
AB  - In this study, a novel dual-energy (DE) material decomposition reconstruction
      algorithm (DEMDRA) was developed using projection data with the aim of reducing
      metal artifacts during digital tomosynthesis (DT) for implants. Using the three
      material decomposition method and decomposition projection data specific for each
      material, a novel DEMDRA was implemented to reduce metal artifacts via weighted
      hybrid reconstructed images [maximum likelihood expectation maximization (MLEM)
      and shift-and-add (SAA)]. Pulsed X-ray exposures with rapid switching between low
      and high tube potential kVp were used for DE-DT imaging, and the images were
      compared using conventional filtered back projection (FBP), MLEM, the
      simultaneous algebraic reconstruction technique total variation (SART-TV),
      virtual monochromatic processing, and metal artifact reduction (MAR)-processing
      algorithms. The reductions in metal artifacts were compared using an artifact
      index (AI), Gumbel distribution of the largest variations, and the artifact
      spread functions (ASFs) for prosthesis phantom. The novel DEMDRA yielded an
      adequately effective overall performance in terms of the AI, and the resulting
      images yielded good results independently of the type of metal used in the
      prosthetic phantom, as well as good noise artifact removal, particularly at
      greater distances from metal objects. Furthermore, the DEMDRA represented the
      minimum in the model of largest variations. Regarding the ASF analysis, the novel
      DEMDRA yielded superior metal artifact reduction when compared with conventional
      reconstruction algorithms with and without MAR processing. Finally, the DEMDRA
      was particularly useful for reducing high-frequency artifacts.

PMID- 30241754
TI  - Robustness of post-reconstruction and direct kinetic parameter estimates under
      rigid head motion in dynamic brain PET imaging.
AB  - OBJECTIVE: Dynamic PET imaging is extensively used in brain imaging to estimate
      parametric maps. Inter-frame motion can substantially disrupt the voxel-wise time
      activity curves (TACs), leading to erroneous maps during kinetic modelling.
      Therefore, it is important to characterize the robustness of kinetic parameters
      under various motion and kinetic model related factors. METHODS: Fully 4D brain
      simulations ([15O]H2O and [18F]FDG dynamic datasets) were performed using a
      variety of clinically observed motion patterns. Increasing levels of head motion
      were investigated as well as varying temporal frames of motion initiation.
      Kinetic parameter estimation was performed using both post-reconstruction kinetic
      analysis and direct 4D image reconstruction to assess bias from inter-frame
      emission blurring and emission/attenuation mismatch. RESULTS: Kinetic parameter
      bias heavily depends on the time point of motion initiation. Motion initiated
      towards the end of the scan results in the most biased parameters. For the
      [18F]FDG data, k4 is the more sensitive parameter to positional changes, while K1
      and blood volume were proven to be relatively robust to motion. Direct 4D image
      reconstruction appeared more sensitive to changes in TACs due to motion, with
      parameter bias spatially propagating and depending on the level of motion.
      CONCLUSION: Kinetic parameter bias highly depends upon the time frame at which
      motion occurred, with late frame motion-induced TAC discontinuities resulting in
      the least accurate parameters. This is of importance during prolonged data
      acquisition as is often the case in neuro-receptor imaging studies. In the
      absence of a motion correction, use of TOF information within 4D image
      reconstruction could limit the error propagation.

PMID- 30241755
TI  - Organ doses from a proton gantry-mounted cone-beam computed tomography system
      characterized with MCNP6 and GATE.
AB  - PURPOSE: To determine organ doses from a proton gantry-mounted cone-beam computed
      tomography (CBCT) system using two Monte Carlo codes and to study the influence
      on organ doses from different acquisition modes and repeated imaging. METHODS:
      The CBCT system was characterized with MCNP6 and GATE using measurements of depth
      doses in water and spatial profiles in air. The beam models were validated
      against absolute dose measurements and used to simulate organ doses from CBCT
      imaging with head, thorax and pelvis protocols. Anterior and posterior 190
      degrees  scans were simulated and the resulting organ doses per mAs were compared
      to those from 360 degrees  scans. The influence on organ doses from repeated
      imaging with different imaging schedules was also investigated. RESULTS: The
      agreement between MCNP6, GATE and measurements with regard to depth doses and
      beam profiles was within 4% for all protocols and the corresponding average
      agreement in absolute dose validation was 4%. Absorbed doses for in-field organs
      from 360 degrees  scans ranged between 6 and 8 mGy, 15-17 mGy and 24-54 mGy for
      the head, thorax and pelvis protocols, respectively. Cumulative organ doses from
      repeated CBCT imaging ranged between 0.04 and 0.32 Gy for weekly imaging and 0.2
      1.6 Gy for daily imaging. The anterior scans resulted in an average increase in
      dose per mAs of 24% to the organs of interest relative to the 360 degrees  scan,
      while the posterior scan showed a 37% decrease. CONCLUSIONS: A proton gantry
      mounted CBCT system was accurately characterized with MCNP6 and GATE. Organ doses
      varied greatly depending on acquisition mode, favoring posterior scans.

PMID- 30241756
TI  - Segmentation improvement through denoising of PET images with 3D-context
      modelling in wavelet domain.
AB  - Positron emission tomography (PET) images have been incorporated into the
      radiotherapy process as a powerful tool to assist in the contouring of lesions,
      leading to the emergence of a broad spectrum of automatic segmentation schemes
      for PET images (PET-AS). However, not all proposed PET-AS algorithms take into
      consideration the previous steps of image preparation. PET image noise has been
      shown to be one of the most relevant affecting factors in segmentation tasks.
      This study demonstrates a nonlinear filtering method based on spatially adaptive
      wavelet shrinkage using three-dimensional context modelling that considers the
      correlation of each voxel with its neighbours. Using this noise reduction method,
      excellent edge conservation properties are obtained. To evaluate the influence in
      the segmentation schemes of this filter, it was compared with a set of Gaussian
      filters (the most conventional) and with two previously optimised edge-preserving
      filters. Five segmentation schemes were used (most commonly implemented in
      commercial software): fixed thresholding, adaptive thresholding, watershed,
      adaptive region growing and affinity propagation clustering. Segmentation results
      were evaluated using the Dice similarity coefficient and classification error. A
      simple metric was also included to improve the characterisation of the filters
      used for induced blurring evaluation, based on the measurement of the average
      edge width. The proposed noise reduction procedure improves the results of
      segmentation throughout the performed settings and was shown to be more stable in
      low-contrast and high-noise conditions. Thus, the capacity of the segmentation
      method is reinforced by the denoising plan used.

PMID- 30241757
TI  - Two-step validation of a Monte Carlo dosimetry framework for general radiology.
AB  - The Monte Carlo technique is considered gold standard when it comes to patient
      specific dosimetry. Any newly developed Monte Carlo simulation framework,
      however, has to be carefully calibrated and validated prior to its use. For many
      researchers this is a tedious work. We propose a two-step validation procedure
      for our newly built Monte Carlo framework and provide all input data to make it
      feasible for future related application by the wider community. The validation
      was at first performed by benchmarking against simulation data available in
      literature. The American Association of Physicists in Medicine (AAPM) report of
      task group 195 (case 2) was considered most appropriate for our application.
      Secondly, the framework was calibrated and validated against experimental
      measurements for trunk X-ray imaging protocols using a water phantom. The dose
      results obtained from all simulations and measurements were compared. Our Monte
      Carlo framework proved to agree with literature data, by showing a maximal
      difference below 4% to the AAPM report. The mean difference with the water
      phantom measurements was around 7%. The statistical uncertainty for clinical
      applications of the dosimetry model is expected to be within 10%. This makes it
      reliable for clinical dose calculations in general radiology. Input data and the
      described procedure allow for the validation of other Monte Carlo frameworks.

PMID- 30241758
TI  - Experimental evaluation of the impact of low tesla transverse magnetic field on
      dose distribution in presence of tissue interfaces.
AB  - PURPOSE: Aim of this study is to experimental evaluate the impact of a 0.35 T
      transverse magnetic field on dose distribution in presence of tissue-air and
      tissue-lung interfaces. METHODS: The investigation was carried out using MRIdian
      (ViewRay, Cleveland, Ohio) and it consisted of comparing experimental
      measurements performed by Gafchromic EBT3 film dosimetry, to Montecarlo
      simulations, carried out in the presence and, as well as, the absence of the
      magnetic field. A preliminary dose calibration was planned on MRIdian, arranging
      3 * 3 cm2 film pieces in a water slab phantom and exposing them at different beam
      on times, in a dose range equal to 0.1-12.1 Gy. All experimental measurements
      were then carried out using the calibrated films and delivering one single beam
      orthogonally to three different phantoms: without inhomogeneity, with an air gap
      and with a lung inhomogeneity. The dose distributions measured by EBT3 films in
      presence of magnetic field were compared to those calculated in the presence and,
      as well as, the absence of the magnetic field, in terms of gamma analysis. A
      quantification of electron return effect (ERE) was also performed. RESULTS: All
      the tested plans considering the magnetic field show a gamma-passing rate higher
      than 98% for 3%/3 mm gamma analysis. In presence of tissue-air interface, the
      electron return effect causes an over-dosage of +31.9% at the first interface and
      an under-dosage of -33% at the second interface. The dosimetric variations in
      presence of tissue-lung interface results to be smaller (+0.8% first interface, 
      1.3% second interface). CONCLUSION: The impact of 0.35 T magnetic field is not
      negligible and it can be effectively modelled by the Montecarlo dose calculation
      platform available in the MRIdian TPS.

PMID- 30241759
TI  - Reducing inter- and intra-planner variability in radiotherapy plan output with a
      commercial knowledge-based planning solution.
AB  - PURPOSE: This study measured to which extent RapidPlan can drive a reduction of
      the human-caused variability in prostate cancer treatment planning. METHODS:
      Seventy clinical prostate plans were used to train a RapidPlan model. Seven
      planners, with different levels of planning experience, were asked to plan a VMAT
      treatment for fifteen prostate cancer patients with and without RapidPlan
      assistance. The plans were compared on the basis of target coverage, conformance
      and OAR sparing. Inter-planner and intra-planner variability were assessed on the
      basis of the Plan Quality Metric formalism. Differences in mean values and
      InterQuartile Ranges between patients and operators were assessed. RESULTS:
      RapidPlan-assisted plans matched manual planning in terms of target coverage,
      homogeneity, conformance and bladder sparing but outperformed it for rectum and
      femoral heads sparing. 8 out of 15 patients showed a statistically significant
      increase in overall quality. Inter-planner variability is reduced in RapidPlan
      assisted planning for rectum and femoral heads while bladder variability was
      constant. The inter-planner variability of the overall plan quality, IQR of PQM%,
      was approximately halved for all patients. RapidPlan assistance induced a larger
      increase in plan quality for less experienced planners. At the same time, a
      reduction in intra-planner variability is measured with a significant overall
      reduction. CONCLUSIONS: The assistance of RapidPlan during the optimization of
      treatments for prostate cancer induces a significant increase of plan quality and
      a contextual reduction of plan variability. RapidPlan is proven to be a valuable
      tool to leverage the planning skills of less experienced planners ensuring a
      better homogeneity of treatment plan quality.

PMID- 30241760
TI  - Reducing the risk of skin injuries in cardiac catheterization procedures:
      Optimization proposal for obese patients.
AB  - PURPOSE: During interventional cardiology procedures, high doses of X-ray may be
      delivered to patients. This is especially critical in cases of obese patients
      and/or high obliquity projections. High dose rates can then be produced in
      patients' skin as well as insufficient image quality due to regulatory
      limitations in the X-ray tube output working in the fluoroscopy mode. In this
      paper, an optimization action is proposed to reduce patient entrance dose rate
      and preserve image quality in cases of thick patients. METHODS: The action is
      based on the evaluation of dose rate to the patient and image quality in a new
      fluoroscopy protocol with less frame rate (7.5 vs. 15 frames/s) and higher
      spectral shape filter (0.4 vs. 0.1 mm Cu). The new protocol is tested in an
      angiography room using a PMMA phantom and a test object. RESULTS: The new
      fluoroscopy protocol (7.5 fr/s and 0.4 mm Cu) reduces entrance surface air kerma
      in 70%-10% (depending on PMMA thickness), preserving the incident air kerma per
      frame at the image detector. While at lower PMMA thickness, the MTF measured with
      bar pattern is better for the default protocol; at PMMA thickness between 32 and
      37 cm, the optimized protocol produces better image quality indicators.
      CONCLUSIONS: This work demonstrates that in the case of high thicknesses of PMMA
      (32-37 cm), increasing spectral beam filter and reducing frame rate may help
      improve image quality and maintain entrance surface air kerma so as to fulfil the
      regulatory requirements.

PMID- 30241761
TI  - Impact of current density on the function and microbial community structure in
      electro-bioreactors.
AB  - The assessment of bacterial communities in wastewater electro-bioreactors has
      garnered attention to improve efficiency of wastewater treatment plant (WWTP)
      processes. This study evaluated the effects of applying different current
      densities on the function and microbial community structure of an electro
      bioreactor by measuring nutrient removal efficiency and analyzing 16S rRNA gene
      high-throughput sequencing. The electro-bioreactors at current density of 3, 5
      and 7 A/m2 resulted in an enrichment of operational taxonomic units belonging to
      distinct functional bacterial families such as (Nitrospiraceae: 8.5, 12.5 and
      12.6% relative abundance, respectively) and (Rhodocyclaceae: 8.1, 8.8 and 9.7%
      relative abundance, respectively), leading to efficient N-removal (>98%) and P
      removal (>98%) higher than the control bioreactor (9.6 and 5.0%, respectively).
      Applying different electric currents proved to affect microbial community
      composition in electro-bioreactors. The results reported here could prove to be
      valuable for process control, optimization and improving WWTPs design and
      operation.

PMID- 30241762
TI  - Corrigendum to "Effect of acidity upon attrition-corrosion of human dental
      enamel" [J. Mech. Behav. Biomed. Mater. 44 (2015) 23-34].

PMID- 30241763
TI  - Resident and Fellow Engagement in Safety and Quality.
AB  - Beyond educational and institutional requirements, there is a need for trainees
      (residents and fellows) to learn patient safety and quality improvement skills in
      order to achieve the ultimate goal of providing better patient care. Key steps to
      engagement include creating a safety and quality culture, supporting faculty
      development, and selecting appropriate curricular resources. Efforts to align the
      goals and processes of the graduate medical education institution and teaching
      hospital can foster a unified mission. Faculty must be prepared to teach and
      reinforce these topics on a regular basis. Both didactic instruction and
      experiential learning are necessary components for trainee education.

PMID- 30241764
TI  - Evaluation and Management of Facial Nerve Schwannoma.
AB  - Facial nerve schwannomas are benign peripheral nerve sheath tumors that arise
      from Schwann cells, and most commonly present with facial paresis and/or hearing
      loss. Computed tomography and MRI are critical to diagnosis. Management decisions
      are based on tumor size, facial function, and hearing status. Observation is
      usually the best option in patients with good facial function. For patients with
      poor facial function, the authors favor surgical resection with facial
      reanimation. There is growing evidence to support radiation treatment in patients
      with progressively worsening moderate facial paresis and growing tumors.

PMID- 30241765
TI  - Preventing and Managing Operating Room Fires in Otolaryngology-Head and Neck
      Surgery.
AB  - Otolaryngologists are at high risk of surgical fire. During surgery in the head
      and neck region there is close proximity of 3 essential elements: an ignition
      source, a fuel, and an oxidizing agent. In this article, the authors highlight
      the scenarios where fire may occur and offer steps that surgeons can take to
      minimize risk for their patients. By understanding the elements of the fire
      triad, otolaryngologists can decrease the risk of surgical fire, through careful
      control of oxidizers, ignition sources, and potential fuels in the operating
      room.

PMID- 30241768
TI  - Easier said than done.

PMID- 30241767
TI  - Limiting paravalvular regurgitation after TAVR: Is better understanding of
      imaging the solution?

PMID- 30241766
TI  - Preventing Childhood Obesity Through a Mindfulness-Based Parent Stress
      Intervention: A Randomized Pilot Study.
AB  - OBJECTIVE: To assess the feasibility of engaging stressed, low-income parents
      with obesity in a novel mindfulness-based parent stress intervention aimed at
      decreasing the risk of early childhood obesity. STUDY DESIGN: An 8-week
      mindfulness-based parent stress group intervention (parenting mindfully for
      health) plus nutrition and physical activity counseling (PMH+N) was developed for
      parents with obesity aimed at preventing obesity in their at-risk 2- to 5-year
      old children. PMH+N was compared with a control group intervention (C+N), and
      improvement in parenting was assessed before and after the intervention using the
      laboratory-based toy wait task (TWT). In addition, nutrition, physical activity,
      and stress were assessed using a multimethod approach. RESULTS: After
      establishing feasibility in 20 parent-child dyads (phase 1), 42 dyads were
      randomized to PMH+N vs C+N (phase 2). Compared with the C+N group, the PMH+N
      group demonstrated significantly better group attendance (P < .015), greater
      improvement in parental involvement (P < .05), and decreased parental emotional
      eating rating (P < .011). Furthermore, C+N, but not PMH+N, was associated with
      significant increases in child body mass index percentile during treatment (P <
      .03) when accounting for the TWT before and after changes in parenting scores.
      CONCLUSIONS: These findings suggest that a mindfulness-based parent stress
      intervention to decrease childhood obesity risk is feasible, requires further
      testing of therapeutic mechanisms in larger samples, and may be a potential way
      to attenuate the risk of childhood obesity. TRIAL REGISTRATION:
      ClinicalTrials.govNCT01974102.

PMID- 30241769
TI  - Undertriage after severe injury among United States trauma centers and the impact
      on mortality.
AB  - INTRODUCTION: Severely injured patients should receive definitive care at high
      acuity trauma centers. The purposes of this study were to determine the
      undertriage (UT) rate within a national sample of trauma centers and to identify
      characteristics of UT patients. METHODS: Severely injured adults >=16 years were
      identified from the 2010-2012 NTDB. UT was defined as those who received
      definitive care or died at hospitals without state or ACS level I or II
      verification. Risk factors for UTT and the impact of UT on mortality were
      determined. RESULTS: Of 348,394 severely injured patients, 11,578 (3.3%) were UT.
      Older, less severely injured, and certain minority patients were most likely to
      be UT. After risk adjustment, predictors of UT included increased age and
      minority race. Increased injury severity and comorbidity were protective (all p <
      .05). Mortality was greater in UT patients regardless of ISS (OR = 1.32, p <
      .001). CONCLUSION: The low UT rate in this study demonstrates the effectiveness
      of triage practices amongst ACS and state verified centers however age, race, and
      insurance disparities in UT should be improved.

PMID- 30241770
TI  - Patentability of time-lapse monitoring has nothing to do with human dignity: A
      response to Alain Pottage.
AB  - In December 2017, Alain Pottage published an article denying the patentability of
      a technique called Time-Lapse Monitoring (TLM). His argument was that this
      procedure, like all other embryo selection procedures, fails to respect human
      dignity. Here, we argue that this statement is mistaken because assisted
      reproductive technologies (ART) require a scarce resource, namely a woman's
      uterus in the right physiological condition. Therefore, embryo selection using
      TLM is entirely appropriate, as it is not possible to guarantee that all of them
      will have access to the environment they need to develop. Hence, the use of
      techniques designed to maximize the number of live births and minimize the
      suffering of women who undergo failed embryo transfers is a moral obligation.

PMID- 30241771
TI  - Towards international standardization of immunoassays for Mullerian inhibiting
      substance/anti-Mullerian hormone.
AB  - RESEARCH QUESTION: Is formulated and lyophilized, recombinant human Mullerian
      inhibiting substance, also known as anti-Mullerian hormone (AMH), suitable for
      the preparation of a WHO international standard to calibrate AMH immunoassays?
      DESIGN: The AMH content of a trial preparation, coded SS-581, was determined by
      five laboratories using seven immunoassay methods. Participants were requested to
      report the content of the preparation in terms of their method calibrators
      through the measurement of a minimum of five concentrations in the linear part of
      the dose-response curve. Participants were also asked to measure, concomitantly,
      a panel of six serum samples containing AMH at concentrations of 0.1-13.0 ng/ml.
      RESULTS: Across all assays, including two automated assays in development, the
      geometric mean content was 361.76 ng/ampoule with a geometric coefficient of
      variation (GCV%) of 39.95%. When measured by immunoassays that were commercially
      available at the time of the study, the mean content was 423.08 ng/ampoule, with
      a GCV% of 26.67%. The inter-method geometric means of five serum samples with an
      AMH concentration >0.3 ng/ml and measured concomitantly with dilutions of SS-581
      varied with a range of GCV% of 14.90-22.35%, which may reflect the use of serum
      sample value transfer to calibrate current immunoassays, some of which use non
      human AMH calibrators. The AMH in trial preparation SS-581 was shown to be
      biologically active in the Mullerian duct regression assay. CONCLUSIONS: A
      reference material prepared using human recombinant AMH is a promising candidate
      for the preparation of an international standard for AMH for immunoassays
      calibrated to recombinant human AMH.

PMID- 30241772
TI  - A critical analysis of advanced practice nursing and nursing specialties.

PMID- 30241773
TI  - Theta network centrality correlates with tDCS response in disorders of
      consciousness.

PMID- 30241774
TI  - Heat not burn tobacco promotion on instagram.

PMID- 30241775
TI  - Understanding susceptibility to e-cigarettes: A comprehensive model of risk
      factors that influence the transition from non-susceptible to susceptible among e
      cigarette naive adolescents.
AB  - The primary objective of this study was to identify risk factors associated with
      becoming susceptible to e-cigarette use over the course of a year among e
      cigarette-naive adolescents considering a comprehensive model of risk factors
      (risk perceptions, social influences and norms, affective risk factors, and other
      behavioral risk factors). Data came from the Texas Adolescent Tobacco and
      Marketing Surveillance system (TATAMS), a longitudinal cohort study of students
      who were in the 6th, 8th, and 10th grades (n = 3907) during the 2014-2015
      academic year. Weighted generalized linear mixed models assessed multiple
      predictors' associated with the transition to susceptibility to e-cigarettes at
      12 months. Among 6th graders, family influence, use of other substances, and
      positive affect were important. Adolescents transitioning from 8th grade to high
      school presented the greatest number of risk factors (e.g., social and normative
      influences). Only sensation seeking increased the risk of susceptibility to e
      cigarettes among 10th graders. Overall, by grade level, incidence of
      susceptibility to e-cigarettes at 12 months did not vary, but risk factor
      profiles varied substantially.

PMID- 30241776
TI  - Internal carotid artery dissection causing pulsatile tinnitus.

PMID- 30241777
TI  - Keeping Slim When Food Is Abundant: What Energy Mechanisms Could Be at Play?
AB  - The obesity epidemic in humans is juxtaposed by observations of passerine birds
      exhibiting fine-scale body mass regulation. The ecology literature is replete
      with research into why these animals regulate body weight, citing tradeoffs
      between competing pressures such as emaciation and predation. Yet studies on the
      underlying mechanisms of mass regulation in these animals are scarce. Maintaining
      or decreasing weight could obviously be achieved by limiting food intake.
      However, there are numerous reasons why an animal may not control ingestion, at
      least precisely. This Opinion article investigates the plausibility of possible
      behavioural and physiological mechanisms to adaptively maintain or decrease body
      mass in birds and other animals. Candidate behavioural mechanisms include
      exercising and fidgeting, while physiological mechanisms could include reducing
      digestive efficiency or mitochondrial efficiency.

PMID- 30241778
TI  - The Peril of Gene-Targeted Conservation.
AB  - The genomics revolution has sparked interest in using our increased understanding
      of the loci involved in phenotypic variation and adaptation to advance the
      conservation of biodiversity. Despite much interest and discussion, it remains
      unclear whether, when, and how such analyses should be used to guide conservation
      action. Such 'gene-targeted' conservation strategies, while promising, are
      complicated by several factors including the complex genomic architecture of
      phenotypic variation and the strong potential for undesirable outcomes such as
      the loss of genome-wide genetic variation and evolutionary potential. We caution
      against relying on gene-targeted approaches as a conservation silver bullet and
      propose rigorous criteria to identify situations where gene-targeted approaches
      are likely to benefit conservation.

PMID- 30241779
TI  - Multidisciplinary care in the hematology clinic: Implementation of geriatric
      oncology.
AB  - Multidisciplinary care is believed to provide benefits to patients with cancer.
      Tumor board conferences as well aspalliative care or psycho-oncological services
      have not only become common in oncology, but also in hematology clinics dedicated
      to the treatment of hematological cancers. Malignant hematological diseases are
      highly prevalent among older persons. Demographic changes in many countries
      worldwide are prompting the integration of geriatric principles, methodology, and
      expertise into existing procedures and infrastructure of multidisciplinary care
      in hematology clinics. Achieving this goal requires the close collaboration or
      even incorporation of multiple new professions in the hematology clinic in order
      to meet the needs of older patients with hematological malignancies who also have
      comorbidities and functional impairments. We here review the rationale, current
      evidence, and practical approaches of integrating geriatric oncology into
      multidisciplinary care in the hematology clinic.

PMID- 30241780
TI  - Osmolality of a fortified human preterm milk: The effect of fortifier dosage,
      gestational age, lactation stage, and hospital practices.
AB  - OBJECTIVE: The purpose of this study was to evaluate the dose-dependent effect of
      human milk fortifier (HMF) on the osmolality of various preterm human milks
      (PHMs) at different gestational and lactation stages, and with different storage
      and treatment conditions that are routinely used in neonatal intensive care units
      (NICUs). STUDY DESIGN: Twenty-four mothers who had given birth to their baby
      before 28 or between 29 and 31 weeks of pregnancy participated in the study after
      1-2 weeks or 3-4 weeks breastfeeding after delivery. The study was a prospective,
      multicenter, comparative, and noninterventional study. Osmolality of fresh or
      pasteurized human milk stored at 4 degrees C was measured (cryoscopy) at
      baseline, and 24hours after adding Suppletine(r) Human Milk fortifier (SHMF) at
      3%, 4%, 4.5%, and 5% (w/v). RESULTS: PHM without supplementation had an
      osmolality (mean+/-SD) of 301+/-8 mOsm/kgH2O (n=40; 95% CI: [298; 303]). Adding 3
      5% SHMF induced a linear increase of osmolality (P<0.001; r2=0.975). With 4%
      SHMF, the osmolality measure was 443+/-13mOsm/kg H2O (95% CI: [439-447]). Neither
      a 24-hour storage at 4 degrees C nor pasteurization induced a modification of
      osmolality compared to the fresh samples. CONCLUSION: Whatever the origin and
      quality of milk as well as hospital practices, adding up to 4% (w/v) SHMF to PHM
      increases its nutritional quality and osmolality without exceeding 450mOsm/kgH2O,
      which is generally recognized as safe.

PMID- 30241781
TI  - A novel chain-based sponge dressing for management of junctional hemorrhage.

PMID- 30241783
TI  - Neuroprotective effects of pramipexole transdermal patch in the MPTP-induced
      mouse model of Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by the selective death of dopaminergic
      neurons. To avoid inconvenience of frequent administration caused by short half
      life and recurrence of symptoms such as tremor and bradykinesia incurred by drug
      elimination, a novel long-acting pramipexole transdermal patch has been made. In
      the present study, we evaluated the neuroprotective effects and underlying
      mechanisms of pramipexole patch (PPX patch) in a subacute PD mouse model induced
      by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that
      PPX patch treatment improved dyskinesia. MPTP-induced reduction of DA as well as
      its metabolites DOPAC and HVA in the striatum were prevented by PPX patch in a
      dose-dependent manner. PPX patch also restored the activity of antioxidant
      enzymes including SOD, GSH-Px and CAT in the striatum while reduced the content
      of MDA. Furthermore, PPX patch upregulated Nrf2/HO-1 expression. The protective
      effects of PPX patch was also associated with downregulation of the Bax/Bcl-2
      ratio and Apaf-1, inhibition of cytochrome c release and inactivation of caspase
      9 and caspase-3. In conclusion, our studies demonstrated that the long-acting
      pramipexole patch exerts its neuroprotective effects, at least in part, by
      inhibiting oxidative stress and mitochondrial apoptosis pathway and holds promise
      as a candidate drug.

PMID- 30241782
TI  - Living in Two Worlds - Children's Experiences After Their Parents' Divorce - A
      Qualitative Study.
AB  - PURPOSE: The aim of this study was to gain a deeper understanding of how children
      living in two homes after parents' separation experience their everyday lives.
      DESIGN AND METHODS: An inductive qualitative design was chosen for the study
      using a hermeneutic phenomenological approach. Twelve children aged 10-13 years,
      and living in two homes, were interviewed. The data analysis used the four
      fundamental lifeworld existential dimensions: "lived body", "lived time", "lived
      space" and "lived human relations" as guidelines for reflections during the
      research process. RESULTS: The overall understanding of the children's experience
      was that living in two homes was like living in two worlds. The children
      struggled with feelings of loss, loyalty and attachment. The children's
      experiences are described in four themes and nine subthemes. The themes are:
      Facing a changing home, Bridging new relations, Longing for continuity, Feeling
      loyalty. CONCLUSIONS: Parents' separation and living in two homes can be
      stressful for children. Children felt torn between their feelings of loyalty
      toward their parents, and their longing for calm and stability in their everyday
      life. A child-centered approach is therefore important to develop support
      focusing on the children's needs and perspectives after their parents' divorces.
      PRACTICE IMPLICATIONS: A deeper understanding of children's experience of living
      in two homes provides nurses who care for children in the community or health
      care service with knowledge of children's need for support. Children whose
      parents have recently divorced, and children who live in families with parents
      experiencing high levels of conflict after the separation need special attention.

PMID- 30241784
TI  - Icariside II attenuates cardiac remodeling via AMPKalpha2/mTORC1 in vivo and in
      vitro.
AB  - Icariside II (ICA II), a flavonoid derived from Epimediumbrevicormum Maxin in,
      has multiple biological activities in Chinese traditional medicine. Our study
      aimed to investigate the potential activity of ICA II against cardiac remodeling
      and the underlying mechanism. Mice received aorta banding (AB) or sham surgery,
      and then were randomly divided into ICA II or vehicle (veh) group for 6 weeks.
      After echocardiography and pressure-volume loop examination, hearts were
      harvested for histopathological analysis and molecular mechanism investigation.
      Additionally, neonatal rat cardiomyocytes (NRCM) were used for in vitro
      experiments. ICA II attenuated the systolic and diastolic cardiac dysfunction,
      and protected mouse heart from hypertrophy and fibrosis. The underlying mechanism
      might involve in the regulation of Akt, AMPKalpha and mTORC. In in vitro
      experiment, ICA II prevented phenylephrine (PE) induced NRCM hypertrophy by
      regulating AMPKalpha/mTORC pathway. This protective effect was disappeared after
      treatment with Compound C (CpC), an AMPKalpha inhibitor. Moreover, ICA II
      activated AMPK at baseline. ICAII was superior to resveratrol in activating
      AMPKalpha and similar to AICAR. ICA II protected against cardiac remodeling and
      NRCM hypertrophy by regulating AMPK/mTORC pathway. ICA II may be a candidate for
      the treatment of malignant cardiac remodeling.

PMID- 30241785
TI  - General overview of blood products in vitro quality: Processing and storage
      lesions.
AB  - Blood products are issued from blood collection. Collected blood is immediately
      mixed with anticoagulant solutions that immediately induce chemical and/or
      biochemical modifications. Collected blood is then transformed into different
      blood products according to various steps of fabrication. All these steps induce
      either reversible or irreversible "preparation-related" lesions that combine with
      "storage-related" lesions. This short paper aims to provide an overview of the
      alterations that are induced by the "non-physiological" processes used to prepare
      blood products that are used in clinical practice.

PMID- 30241786
TI  - Application of metal-organic framework MIL-101(Cr) to microextraction in packed
      syringe for determination of triazine herbicides in corn samples by liquid
      chromatography-tandem mass spectrometry.
AB  - In this work, a metal-organic framework material MIL-101(Cr) was prepared and
      used as the sorbent for a laboratory-made semi-automated microextraction in
      packed syringe (MEPS). Six triazine herbicides, including desmetryn, prometon,
      ametryn, prometryn, atraton, and dipropetryn, that are commonly found in corn
      samples, were extracted and determined by the MEPS method and high performance
      liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Key parameters
      affecting the extraction efficiencies, including type of extraction solvent, type
      and amount of sorbent, time of ultrasonic extraction and adsorption, and type,
      volume and flow rate of elution solvent, were investigated. The limits of
      detection (LODs, S/N = 3) and quantification (LOQs, S/N = 10) for all analytes
      obtained by the proposed method were in the ranges of 0.01-0.12 ng g-1 and 0.04
      0.35 ng g-1, respectively, which were far lower than that of reported methods.
      The findings indicated that the proposed semi-automated MEPS method was easy and
      efficient for the extraction of triazine herbicides in corn samples.

PMID- 30241787
TI  - Feasibility of a Kinect(r)-based rehabilitation strategy after burn injury.
AB  - INTRODUCTION: The advent of consoles that deliver both interactive games and
      therapy may augment rehabilitation options in burn patients. The Jintronix
      software combines therapy-specific software and interactive gaming as a form of
      coaching and records patient performance on the Kinect(r) platform. Our objective
      was to determine the feasibility of a set of Jintronix games and therapy modules
      in hospitalized adult burn patients. METHODS: We conducted a prospective single
      center feasibility study from August through October 2016. The study enrolled
      subjects to conduct 1 supervised session with 6 Jintronix modules targeting their
      burned areas of the body, with an acceptability survey and a safety analysis. We
      also performed qualitative analysis to detect major themes from free-text
      responses. RESULTS: We enrolled 20 participants. Eleven (55%) completed all the
      modules; reasons for incompletion included baseline shoulder abduction pain and
      poor balance. Participants responded that the activity was comfortable (90%),
      safe (100%), easy to understand (95%), and improved strength/range of motion
      (100%). Mean module completion time was 43+/-10min. Mean pain score was 3.8+/-2.8
      (out of 10) and localized to burned areas. The wall climbing module had 4
      episodes of temporary imbalance. Eight (40%) participants recorded fatigue at
      completion and noted "sweating" or "feeling stretched". Qualitative analysis
      highlighted that the activity was "fun/cool" and a "good challenge". Negative
      themes included "inaccurate depth" sensing and "too lengthy" on a specific
      module. CONCLUSIONS: A Jintronix-based therapy demonstrated good acceptability
      and safety in hospitalized burn patients. Feedback from this study led to
      software modifications implemented by the Jintronix company. This feasibility
      study has informed the design of a prospective randomized controlled trial to
      determine whether a virtual-environment home rehabilitation strategy improves
      functional outcomes after burn injury.

PMID- 30241788
TI  - Minimum breast distance largely explains individual variability in doses to
      contralateral breast from breast-cancer radiotherapy.
AB  - PURPOSE: To provide personalized estimates of doses to contralateral breast (CB)
      from breast-cancer radiotherapy. METHODS: Whole-breast irradiations using 3D
      conformal, intensity-modulated and hybrid techniques with 50.4 Gy prescribed dose
      were planned for 128 breast-cancer patients. From their CT images, 17 anatomic
      measures were assessed and tested by model fitting as predictors for CB dose
      volume characteristics. RESULTS: Multi-field intensity-modulated radiotherapy
      (IMRT) yielded mean CB doses of 0.8-7.1 Gy, with no correlation to the studied
      anatomic parameters. Tangential whole-breast irradiation led to much lower mean
      CB doses, 0.2-1.6 Gy. About 60% of this inter-patient variability was explained
      by individual variations in a single anatomic measure, the minimum breast
      distance (MBD), defined as the CB distance from the tangent to the treated
      breast. Per 1 cm increase in MBD, the mean CB dose decreased by 10-15%. As an
      alternative to MBD, dose estimates could be based on the breast-to-breast
      distance, which is highly correlated with MBD. CONCLUSION: The results enable
      personalized assessment of CB doses from tangential whole-breast irradiation,
      based only on parameters assessable from CT data. This may help support clinical
      decision-making processes as well as analyse retrospective studies on CB risks.

PMID- 30241790
TI  - In response to Rydzewski NR et al. "Role of adjuvant external beam radiotherapy
      and chemotherapy in one versus two or more node-positive vulvar cancer: A
      National Cancer Database study".

PMID- 30241789
TI  - External validation of an NTCP model for acute esophageal toxicity in locally
      advanced NSCLC patients treated with intensity-modulated (chemo-)radiotherapy.
AB  - BACKGROUND AND PURPOSE: We externally validated a previously established
      multivariable normal-tissue complication probability (NTCP) model for Grade >=2
      acute esophageal toxicity (AET) after intensity-modulated (chemo-)radiotherapy or
      volumetric-modulated arc therapy for locally advanced non-small cell lung cancer.
      MATERIALS AND METHODS: A total of 603 patients from five cohorts (A-E) within
      four different Dutch institutes were included. Using the NTCP model, containing
      predictors concurrent chemoradiotherapy, mean esophageal dose, gender and
      clinical tumor stage, the risk of Grade >=2 AET was estimated per patient and
      model discrimination and (re)calibration performance were evaluated. RESULTS:
      Four validation cohorts (A, B, D, E) experienced higher incidence of Grade >=2
      AET compared to the training cohort (49.3-70.2% vs 35.6%; borderline significant
      for one cohort, highly significant for three cohorts). Cohort C experienced lower
      Grade >=2 AET incidence (21.7%, p < 0.001). For three cohorts (A-C),
      discriminative performance was similar to the training cohort (area under the
      curve (AUC) 0.81-0.89 vs 0.84). In the two remaining cohorts (D-E) the model
      showed poor discriminative power (AUC 0.64 and 0.63). Reasonable calibration
      performance was observed in two cohorts (A-B), and recalibration further improved
      performance in all three cohorts with good discrimination (A-C). Recalibration
      for the two poorly discriminating cohorts (D-E) did not improve performance.
      CONCLUSIONS: The NTCP model for AET prediction was successfully validated in
      three out of five patient cohorts (AUC >=0.80). The model did not perform well in
      two cohorts, which included patients receiving substantially different treatment.
      Before applying the model in clinical practice, validation of discrimination and
      (re)calibration performance in a local cohort is recommended.

PMID- 30241791
TI  - Treatment of brain metastases with stereotactic radiosurgery and immune
      checkpoint inhibitors: An international meta-analysis of individual patient data.
AB  - BACKGROUND AND PURPOSE: While the combination of stereotactic radiosurgery (SRS)
      and immune checkpoint inhibitors (ICI) is becoming more widely used in the
      treatment of brain metastases (BM), there is a paucity of prospective data to
      validate both the safety and efficacy, as well as the optimal timing of these two
      therapies relative to one another. METHODS: A PICOS/PRISMA/MOOSE selection
      protocol was used to identify 17 studies across 15 institutions in 3 countries.
      Inclusion criteria were patients: diagnosed with BM; treated with SRS/ICI, either
      concurrently or non-concurrently; with at least one of the primary or secondary
      outcome measures reported. Weighted random effects meta-analyses using the
      DerSimonian and Laird method were performed. The primary outcome was 1-year
      overall survival (OS). Secondary outcomes were 1-year local control (LC), 1-year
      regional brain control (RBC), and radionecrosis incidence. RESULTS: A total of
      534 patients with 1,570 BM were included. The 1-year OS was 64.6% and 51.6% for
      concurrent and non-concurrent therapy, respectively (p < 0.001). Local control at
      1-year was 89.2% and 67.8% for concurrent and non-concurrent therapy,
      respectively (p = 0.09). The RBC at 1-year was 38.1% and 12.3% for concurrent and
      ICI administration prior to SRS, respectively (p = 0.049). The overall incidence
      of radionecrosis for all studies was 5.3%. CONCLUSIONS: Concurrent administration
      of SRS/ICI may be associated with improved safety and efficacy versus sequential
      therapy. These findings, however, are hypothesis-generating and require further
      validation by ongoing and planned prospective trials.

PMID- 30241792
TI  - Coffee and wine consumption is associated with reduced mortality from alcoholic
      liver disease: follow-up of 219,279 Norwegian men and women aged 30-67 years.
AB  - PURPOSE: To study the association between coffee and alcoholic beverage
      consumption and alcoholic liver disease mortality. METHODS: In total, 219,279 men
      and women aged 30-67 years attended cardiovascular screening in Norway from 1994
      to 2003. Linkage to the Cause of Death Registry identified 93 deaths from
      alcoholic liver disease. Coffee consumption was categorized into four levels: 0,
      1-4, 5-8, and greater than or equal to 9 cups/d and alcohol consumption as 0,
      greater than 0 to less than 1.0, 1.0 to less than 2.0, and greater than or equal
      to 2.0 units/d, for beer, wine, liquor, and total alcohol consumption. RESULTS:
      The hazard ratios per one category of consumption were 2.06 (95% confidence
      interval 1.62-2.61), 0.68 (0.46-1.00), and 2.54 (1.92-3.36) for beer, wine, and
      liquor, respectively. Stratification at 5 cups/d (the mean) revealed a stronger
      association between alcohol consumption and alcoholic liver disease at less than
      5 versus 5 or more cups/d. With less than 5 cups/d, 0 alcohol units/d as
      reference, the hazard ratio reached to 25.5 (9.2-70.5) for greater than or equal
      to 2 units/d, whereas with greater than or equal to 5 cups/d, it reached 5.8 (1.9
      17.9) for greater than or equal to 2 units/d. A test for interaction was
      significant (P = .01). CONCLUSIONS: Coffee and wine consumption were inversely
      associated with alcoholic liver disease death. Total alcohol consumption was
      adversely associated with alcoholic liver disease mortality and the strength of
      the association varied with the level of coffee consumption.

PMID- 30241793
TI  - Predictors of Adherence and Treatment Delays among African American Women
      Recommended to Receive Breast Cancer Chemotherapy.
AB  - BACKGROUND: Recognition of potential explanations for nonadherence or treatment
      delays is crucial to improving survival, particularly among African American
      women, for whom there is limited research assessing patient factors that
      influence adherence to breast cancer chemotherapy. OBJECTIVE: This study sought
      to examine the association of patient factors such as age, income, employment,
      and partner status with adherence (full dose/on time) to prescribed breast cancer
      adjuvant chemotherapy and delays in treatment among African American women.
      METHODS: This observational, prospective study used baseline data from the
      Adherence, Communication, Treatment, and Support Intervention Study that included
      African American women with early stage breast cancer who were recommended to
      receive chemotherapy. Eleven baseline demographic variables measured by a
      sociodemographic questionnaire were analyzed against the outcome variables of 85%
      adherence to chemotherapy, dichotomized as yes or no, and chemotherapy treatment
      delays measured as number of days. RESULTS: For the 121 African American women
      included in this study, only employment status and number of comorbidities were
      significant predictors for total treatment delays (incidence rate ratio [IRR] =
      2.175 [p = .000]; IRR = 1.234 [p = .003]) in the adjusted models. IMPLICATIONS:
      Employment status and number of comorbidities are predictors of the ability to
      receive timely breast cancer chemotherapy among African American women. This
      knowledge allows identification of patients in need of tailored supportive care
      to encourage adherence and prevent treatment delays.

PMID- 30241795
TI  - Nomogram prediction of individual prognosis of patients with acute-on-chronic
      hepatitis B liver failure.
AB  - BACKGROUND: The current definitions and etiologies of acute-on-chronic liver
      failure (ACLF) are clearly very different between East and West. AIMS: This study
      aimed to develop an effective prognostic nomogram for acute-on-chronic hepatitis
      B liver failure (ACHBLF) as defined by the Asia Pacific Association for the Study
      of the Liver (APASL). METHODS: The nomogram was based on a retrospective study of
      573 patients with ACHBLF, defined according to the APASL, at the Beijing Ditan
      Hospital. The results were validated using a bootstrapped approach to correct for
      bias in two external cohorts, including an APASL ACHBLF cohort (10 hospitals, N =
      329) and an EASL-CLIF ACHBLF cohort (Renji Hospital, N = 300). RESULTS:
      Multivariate analysis of the derivation cohort for survival analysis helped
      identify the independent factors as age, total bilirubin, albumin, international
      normalized ratio, and hepatic encephalopathy, which were included in the
      nomogram. The predictive value of nomogram was the strongest compared with CLIF-C
      ACLF, MELD and MELD-Na and similar to COSSH-ACLF in both the derivation and
      prospective validation cohorts with APASL ACHBLF, but the CLIF-C ACLF was better
      in the EASL-CLIF ACHBLF cohort. CONCLUSIONS: The proposed nomogram could
      accurately estimate individualized risk for the short-term mortality of patients
      with ACHBLF as defined by APASL.

PMID- 30241796
TI  - Health workforce planning: which countries include nurse practitioners and
      physician assistants and to what effect?
AB  - BACKGROUND: An increasing number of countries are introducing new health
      professions, such as Nurse Practitioners (NPs) and Physician Assistants (PAs).
      There is however limited evidence, on whether these new professions are included
      in countries' workforce planning. METHODS: A cross-country comparison of
      workforce planning methods. Countries with NPs and/or PAs were identified,
      workforce planning projections reviewed and differences in outcomes were
      analysed, based on a review of workforce planning models and a scoping review.
      Data on multi-professional (physicians/NPs/PAs) vs. physician-only models were
      extracted and compared descriptively. Analysis of policy implications was based
      on policy documents and grey literature. RESULTS: Of eight countries with
      NPs/PAs, three (Canada, the Netherlands, United States) included these
      professions in their workforce planning. In Canada, NPs were partially included
      in Ontario's needs-based projection, yet only as one parameter to enhance
      efficiency. In the United States and the Netherlands, NPs/PAs were covered as one
      of several scenarios. Compared with physician-only models, multi-professional
      models resulted in lower physician manpower projections, primarily in primary
      care. A weakness of the multi-professional models was the accuracy of data on
      substitution. Impacts on policy were limited, except for the Netherlands.
      CONCLUSIONS: Few countries have integrated NPs/PAs into workforce planning. Yet,
      those with multi-professional models reveal considerable differences in projected
      workforce outcomes. Countries should develop several scenarios with and without
      NPs/PAs to inform policy.

PMID- 30241794
TI  - Associations between Pregnancy Intention, Attitudes, and Contraceptive Use among
      Women Veterans in the ECUUN Study.
AB  - BACKGROUND: Although pregnancy intention is strongly associated with
      contraceptive use, little is known about the interaction between pregnancy
      intention and attitude, or how they jointly affect contraceptive use. METHODS:
      Cross-sectional data from a national survey of women veterans who receive care
      within the Veterans Affairs Healthcare System were used to examine relationships
      among pregnancy intention (in next year, in >1 year, never, not sure), attitude
      toward hypothetical pregnancy (worst thing, neutral, best thing), and
      contraceptive use among women at risk for unintended pregnancy. Bivariate and
      multivariable analyses assessed associations between pregnancy intention and
      attitude, both separately and jointly, with contraceptive use. Multinomial
      regression assessed the relationship of intention and attitude with contraceptive
      method effectiveness. RESULTS: Among 858 women at risk of unintended pregnancy,
      bivariate analysis demonstrated that pregnancy intention and attitude were
      associated, but not perfectly aligned. In logistic regression models including
      both variables, intention of never versus in next year (adjusted odds ratio
      [aOR], 2.78; 95% confidence interval [CI], 1.34-5.75) and attitude of worst thing
      versus best thing (aOR, 2.86; 95% CI, 1.42-5.74) were each positively associated
      with contraception use. Among women using contraception, intention of never (aOR,
      3.17; 95% CI, 1.33-7.59) and attitude of worst thing (OR, 2.09; 95% CI, 1.05
      4.17) were associated with use of highly effective (e.g., intrauterine devices
      and implants) versus least effective (e.g., barrier) methods. CONCLUSIONS: These
      findings support prior research suggesting that pregnancy intention alone does
      not fully explain contraceptive behaviors and imply that attitude toward
      pregnancy plays an important role in shaping contraceptive use independent of
      pregnancy intentions.

PMID- 30241797
TI  - Surviving niche busters: Main strategies employed by Canadian private insurers
      facing the arrival of high cost specialty drugs.
AB  - The Canadian patchwork system of prescription drug coverage and the employer
      sponsored private health benefits group plans appear vulnerable to cost growth
      due to insufficient balance of power between fragmented public and private
      buyers, and pharmaceutical manufacturers. The emergence of "bad" insurance risks
      caused by new and very expensive treatments featuring high cost specialty
      medicines - also known as niche buster drugs - exposes this vulnerability. This
      study fills a gap in knowledge by seeking to better understanding how Canadian
      private insurers face the arrival of specialty pharmaceuticals. It completes an
      overview of a body of grey literature composed of publicly available online
      articles from the employment benefits and group insurance consulting and
      administration industry; online documents from group benefits sector conferences;
      and online or on demand materials from Canadian life and health insurers. Claims
      for high cost specialty drugs generate new bad insurance risks that Canadian
      health insurers attempt to mitigate through isolated corporate initiatives,
      industry-wide strategies and calls for universal, public catastrophic coverage.
      The outcomes of these strategies are limited cost-control measures as well as
      risk and cost transfers onto plan sponsors, patients and provincial public
      programs.

PMID- 30241798
TI  - Postgraduate Global Health Competency Profile for Radiation Oncology.
AB  - AIMS: To identify core competencies for postgraduate radiation oncology trainees
      in global health and cancer that may inform revisions across radiation oncology
      residency specialty training curricula. MATERIALS AND METHODS: A review of the
      literature was conducted to identify all potential global health competency
      items. An international two-phase Delphi process was conducted with experts in
      oncology. In phase 1, all experts scored, on a nine-point Likert scale, the
      degree to which they agreed an item should be included in the competency profile.
      Items with a mean score >=7 were included, those scoring 4-6 were reviewed in
      phase 2, and items scored <=3 were excluded. In phase 2, items were discussed and
      subsequently ranked for inclusion or exclusion in the competency profile. Items
      with >75% voting for inclusion were included in the final competency profile.
      RESULTS: In total, 142 potential global health competency items were identified.
      Sixty-one items were removed as redundant or irrelevant, leaving 81 items for the
      Delphi process. Eighteen specialists were invited to participate, with 10 (56%)
      agreeing to participate in phase 1 of the Delphi process. Participants
      represented 10 centres in seven countries. Of the 81 items ranked in phase 1, 72
      items (89%) had a mean score >=7 and were automatically included in the final
      competency profile. The remaining nine items received a score of 4-6 and were
      discussed in phase 2 of the Delphi process, of which three received <75%
      agreement for inclusion and were excluded. The result was a final list of 78
      enabling competency items. CONCLUSIONS: The radiation oncology global health
      competency profile represents an international consensus on the items that can
      inform radiation oncology training requirements.

PMID- 30241799
TI  - Shear wave elastography can assess the in-vivo nonlinear mechanical behavior of
      heel-pad.
AB  - This study combines non-invasive mechanical testing with finite element (FE)
      modelling to assess for the first time the reliability of shear wave (SW)
      elastography for the quantitative assessment of the in-vivo nonlinear mechanical
      behavior of heel-pad. The heel-pads of five volunteers were compressed using a
      custom-made ultrasound indentation device. Tissue deformation was assessed from B
      mode ultrasound and force was measured using a load cell to calculate the force -
      deformation graph of the indentation test. These results were used to design
      subject specific FE models and to inverse engineer the tissue's hyperelastic
      material coefficients and its stress - strain behavior. SW speed was measured for
      different levels of compression (from 0% to 50% compression). SW speed for 0%
      compression was used to assess the initial stiffness of heel-pad (i.e. initial
      shear modulus, initial Young's modulus). Changes in SW speed with increasing
      compressive loading were used to quantify the tissue's nonlinear mechanical
      behavior based on the theory of acoustoelasticity. Statistical analysis of
      results showed significant correlation between SW-based and FE-based estimations
      of initial stiffness, but SW underestimated initial shear modulus by 64%(+/-16).
      A linear relationship was found between the SW-based and FE-based estimations of
      nonlinear behavior. The results of this study indicate that SW elastography is
      capable of reliably assessing differences in stiffness, but the absolute values
      of stiffness should be used with caution. Measuring changes in SW speed for
      different magnitudes of compression enables the quantification of the tissue's
      nonlinear behavior which can significantly enhance the diagnostic value of SW
      elastography.

PMID- 30241800
TI  - Hypophosphorous acid cross-linked layer-by-layer assembly of green
      polyelectrolytes on polyester-cotton blend fabrics for durable flame-retardant
      treatment.
AB  - In this work, a facile method to manufacture the layer-by-layer (LbL) assembled
      coating with durable flame-resistant effect on the polyester-cotton blend fabrics
      was reported. The LbL coating modified polyester-cotton fabric was treated with
      positively charged polyethyleneimine (PEI) and negatively charged oxidized sodium
      alginate (OSA) successively. Subsequently, the PEI/OSA coating was cross-linked
      by hypophosphorous acid (HA). As characterized by X-ray photoelectron
      spectroscopy and scanning electron microscopy, the HA cross-linked PEI/OSA
      coatings were successfully deposited on the surfaces of polyester and cotton
      fibers. Effects of the as-prepared coating on thermal stability, flame retardancy
      and laundering durability of the polyester-cotton blend fabrics were
      investigated. Thermogravimetric analysis revealed that the thermal decomposition
      of modified polyester-cotton fabric could be retarded obviously compared with the
      untreated one, as evidenced by the improvement in the 5% mass loss temperature by
      30  degrees C. In the horizontal burning test, self-extinguishing behavior could
      be achieved for the polyester-cotton fabric treated with 5 bilayers coating.
      Moreover, the 77% and 75% reduction in the peak heat release rate and total heat
      release were observed for the polyester-cotton fabric treated with 10 bilayers
      coating. The treated fabrics still showed good flame retardant performance after
      12 laundering cycles.

PMID- 30241801
TI  - Nanosilicate embedded agarose hydrogels with improved bioactivity.
AB  - This paper reports the synthesis of nanocomposite agarose hydrogels with improved
      bioactivity with the incorporation of anisotropic 2D nanosilicates (Laponite) to
      promote cell binding, growth and proliferation. Rheological measurements showed
      that the incorporation of nanosilicates slightly increased the gelation
      temperature (Tgel). The use of higher nanosilicate content at the constant
      agarose concentration improved the mechanical properties of the gels. Due to the
      non-swelling nature of agarose, the addition of nanosilicates did not result in
      any remarkable change in the swelling properties of the agarose gels, while
      collapsed agarose nanofibers were observed with the incorporation of
      nanosilicates. EDX analysis confirmed the presence of the embedded nanosilicates
      in the gel matrix. The existence of physical interactions between nanosilicate
      and agarose was demonstrated by FTIR over the shifting of SiO stretching band to
      a lower frequency. The encapsulated NIH/3T3 fibroblast cells showed enhanced
      proliferation and spreading in the presence of nanosilicates.

PMID- 30241802
TI  - In vitro bioactivity and cytotoxicity of films based on mesocarp of Orbignya sp.
      and carboxymethylcellulose as a tannic acid release matrix.
AB  - This study aims to obtain mesocarp films of Orbignya sp. (MB) and
      carboxymethylcellulose (CMC) for application as a drug release matrix. Tannic
      acid (TA) was used as a standard drug. The films were evaluated by infrared,
      swelling power, TA release profile, bioactivity and in vitro cytotoxicity.
      Infrared results indicated absorption at 1.205 cm-1, which is characteristic of
      ester group from the incorporated tannin. The MB-CMC film had 449.15% swelling
      power, release of 71.01% of TA of the matrix after 24 h. Films showed scavenger
      activity of radicals DPPH (79.07 +/- 1.71% to 82.17 +/- 1.94%) and ABTS+ (82.20
      +/- 0.30% to 88.90 +/- 1.05). The MB-CMC film also showed in vitro cytotoxicity
      on sarcoma-180 (91.86 +/- 9.97%) and on promastigote forms of Leishmania major
      (100%). Polymers showed good compatibility in the mixture and the results suggest
      the films obtained are promising as drug release matrices.

PMID- 30241803
TI  - Effective degradation of curdlan powder by a novel endo-beta-1->3-glucanase.
AB  - Curdlan is a water-insoluble microbial exo-polysaccharide that is hardly
      degraded. The gene CcGluE encoding an endo-beta-1->3-glucanase consisting of 412
      amino acids (44 kDa) from Cellulosimicrobium cellulans E4-5 was cloned and
      expressed in Escherichia coli. The recombinant CcGluE hydrolysed curdlan powder
      effectively. CcGluE shows high endo-beta-1->3 glucanase activity and low beta-1,4
      and beta-1,6 glucanase activities with broad substrate specificity for glucan,
      including curdlan, laminarin and beta-1->3/1->6-glucan, and the highest catalytic
      activity for curdlan. Moreover, the hydrolytic products of curdlan were glucan
      oligosaccharides with degrees of polymerisation of 2-13, and the main products
      were glucobiose and glucotriose. Degradation mode analysis indicated that CcGluE
      is more likely to hydrolyse glucopentaose and revealed that CcGluE was an endo
      glucanase. Furthermore, upon combination with a homogenising pre-treatment method
      with curdlan, the degradation efficiency of CcGluE for curdlan powder was greatly
      improved 7.1-fold, which laid a good foundation for the utilisation of curdlan.

PMID- 30241805
TI  - Pore structure and pertinent physical properties of nanofibrillated cellulose
      (NFC)-based foam materials.
AB  - Nanofibrillated cellulose (NFC)-based foam materials have broad prospects in
      replacing traditional foams, due to its facile natural biodegradation. This study
      addressed the relationship between the foam preparation process parameters and
      resulting pore structure. An aqueous NFC suspension was freeze-dried while adding
      an organic solvent, ethanol, to adjust the curing process. The effects of the
      solid content and freeze-drying temperature on the microstructure and mechanical
      stability as well as heat transfer performance of the produced NFC-based foam
      were investigated. The foam obtained at a 3%-5% solid content featured a well
      defined lamellar and interlayer pillar support structure. With an increase in the
      solid content, the average wall thickness increased whereas the average pore area
      decreased. Yet the pore density increased with the pore distribution becoming non
      uniform. With a decrease in freezing temperature, the wall thickness decreased
      (with no wall structure at -196  degrees C) but the pore density increased, with
      the pores being distributed more uniformly. The foam mechanical strength and
      thermal conductivity were found to be linked to porosity. The foam material had
      the most suitable mechanical and thermal insulation properties when prepared with
      a 5% solid content at a freeze-drying temperature of -55  degrees C.

PMID- 30241804
TI  - Glutathione responsive chitosan-thiolated dextran conjugated miR-145
      nanoparticles targeted with AS1411 aptamer for cancer treatment.
AB  - miR-145 is a tumor suppressive miRNA which is abnormally reduced in different
      cancers. miR-145 overexpression reduces cancer migration, invasion, and cell
      adhesion. Increasing miR-145 level using suitable and efficient gene delivery
      systems could be valuable in cancer treatment. In this study, a redox-responsive
      miR-145 conjugated thiolated dextran (TD-miR) was prepared. Also, polyelectrolyte
      complexes (PECs) of TD-miR and chitosan were fabricated and decorated with anti
      nucleolin aptamer, AS1411 (apt-PEC). The size of the PECs was between 40-270 nm,
      and the zeta potential was varied according to the TD-miR to chitosan molar
      ratio. The outcomes of cellular studies indicated the excellence of the apt-PEC
      as a duel targeted delivery system and the PECs composed of chitosan 18 kDa with
      TD-miR to chitosan ratio of 5. TD-miR and the PECs are appropriate as the smart
      gene delivery systems which preserve and transfect the cargo and release it in
      cytoplasm.

PMID- 30241806
TI  - Synthesis, structural and in-vitro characterization of beta-cyclodextrin grafted
      L-phenylalanine functionalized graphene oxide nanocomposite: A versatile
      nanocarrier for pH-sensitive doxorubicin delivery.
AB  - To enhance graphene stability, drug loading capacity and biocompatibility, beta
      cyclodextrin (beta-CD) was grafted onto graphene oxide (GO) using L-plenylalanine
      (Phe) as a linker. The doxorubicin (DOX) loading efficiency and capacity of GO
      Phe-CD were 78.7% and 85.2%, respectively. The cone shaped cavity of CD acts as a
      host for DOX loading through inclusion complex formation. The GO-Phe-CD
      nanocarrier showed higher release ratio of DOX in acidic milieu of cancer cells.
      In addition, general cytotoxicity of the nanocarriers was examined by MTT assay
      and trypan blue dye exclusion in MCF-7 cell lines. It was established that the
      MTT assay was not an appropriate technique for predicting the cytotoxicity of
      graphene based nanocarriers due to the spontaneous formation of MTT formazan by
      these materials; leading to a false high biocompatibility. According to the
      trypan blue experiment, the GO-Phe-CD had significant cytocompatibility, and the
      DOX-loaded GO-Phe-CD had outstanding killing capability to MCF-7 cells.

PMID- 30241807
TI  - Ultrasonic-microwave synthesis of ZnO/BiOBr functionalized cotton fabrics with
      antibacterial and photocatalytic properties.
AB  - ZnO coated fabrics have attracted wide attentions due to their antibacterial and
      photocatalytic self-cleaning properties. However, the photo-response of ZnO only
      in ultraviolet region limits its application. In this paper, ZnO/BiOBr
      functionalized cotton fabrics were synthesized by a facile and time-saving
      ultrasonic-microwave combined method. Compared with ZnO coated fabric, the
      photocatalytic activity of ZnO/BiOBr coated fabric under visible light
      irradiation was remarkably improved at no sacrifice of its antibacterial
      activity. Simultaneously, it also showed good resistance to bacterial adhesion
      and photocorrosion. The introduction of two-dimensional BiOBr nanoflakes not only
      enhanced the visible light absorption, but also reduced the recombination rate of
      electron-hole pairs, thus significantly improving the photocatalytic self
      cleaning performance of the coated fabric under visible light irradiation. The
      ZnO/BiOBr coated cotton fabric with both antibacterial and self-cleaning
      functionalities may have broad application prospects in the fields of textile,
      medicine and chemical industry.

PMID- 30241808
TI  - Chitosan nanoparticles via high-pressure homogenization-assisted miniemulsion
      crosslinking for mixed-matrix membrane adsorbers.
AB  - Glutaraldehyde-crosslinked chitosan nanoparticles (Chi-NPs) were prepared
      reproducibly via miniemulsion crosslinking for effective adsorption of the active
      pharmaceutical ingredient (API) Diclofenac (DCL). Three different molecular
      weights (MWs) of highly deacetylated (>90%) chitosans (low, medium and high MW)
      were used to vary the disperse phase viscosity. Particle formation was evaluated
      ranging from one to seven homogenization cycles at 40 MPa. Particles were
      prepared successfully with the low and medium MW chitosan in the range of 125 nm
      250 nm (z-average). In HPLC assisted, static adsorption experiments, all
      particles showed a rapid sorption rate (<2 min) with an adsorption capacity of up
      to 256.2 mg g-1 DCL. Modelling of adsorption isotherms resulted in a qmax 358.3
      mg g-1 for Langmuir and 502.5 mg g-1 for Sips, respectively. Membrane adsorbers
      were prepared by processing Chi-NPs into porous polyether sulfone microfiltration
      membranes via a casting and phase inversion process, resulting in an adsorption
      capacity of up to 3.6 mg m-2 DCL in dynamic adsorption experiments.

PMID- 30241809
TI  - Regeneration of cellulose dissolved in ionic liquid using laser-heated melt
      electrospinning.
AB  - A "green" and highly efficient route was proposed to fabricate ultrafine
      cellulose fibers. The processing steps include cellulose dissolution, gel
      preparation, melt-electrospinning and fiber coagulation. High DP cellulose can be
      easily dissolved in 1-butyl-3-methylimidazolium chloride (BmimCl) when the blend
      was stirred at 110  degrees C for 2 h. The maximum solubility can reach up to
      16.7 wt%. A homogeneous ternary cellulose/BmimCl/ethanol or
      cellulose/BmimCl/water gel was made by the methods of crystallization and casting
      for the purpose of fixing the shape of the cellulose/BmimCl solution. After laser
      heating and electrospinning, multiple jets were ejected from the gel tip and then
      frozen on a super cold target. Pure cellulose fibers without beads and blocks
      were achieved after coagulation. The results of WAXD and FTIR indicated that the
      regenerated cellulose fibers were amorphous and chemically stable. More
      importantly, this approach can be applied to other polysaccharides for the
      preparation of ultrafine fibers.

PMID- 30241810
TI  - Structure characterization and hypoglycemic activity of an arabinogalactan from
      Phyllostachys heterocycla bamboo shoot shell.
AB  - An arabinogalactan (PBSS2) was fractionated from the bamboo shoot shell of
      Phyllostachys heterocycla. Structural analysis indicated that PBSS2 was mainly
      composed of galactose, arabinose, xylose and galacturonic acid in a ratio of
      7.8:6.3:1.4:1.0. It was a 1,3- linked beta-d-galactan having 61.1% degree of
      branching at the O-6 positions. The three branches consisting of 1,4-linked beta
      d-Xylp terminated with beta-d-Galp, 1,5-linked alpha-L-Araf inserted with 1,4
      alpha-6-O-Me-d-GalpA and 1,3,5-linked alpha-L-Araf terminated by alpha-L-Araf.
      Furthermore, its chain conformation on the values of weight-average molecular
      weight (Mw), the radius of gyration (Rg) and intrinsic viscosity ([eta]) were
      found as following: 7.36 * 104 g/mol, 12.8 nm and 17.7 mL/g, which was evidenced
      by AFM. The structure exponent of alpha (0.38) and df (2.17) revealed it existed
      as a sphere-like chain in NaNO3 aqueous solution. In vitro Caco-2 cells assay
      showed that PBSS2 presented positive effect on the inhibition of glucose
      absorption in time-dependent manner at relatively high concentration.

PMID- 30241811
TI  - Cytotoxicity against cancer cells of chitosan oligosaccharides prepared from
      chitosan powder degraded by electrical discharge plasma.
AB  - Chitosan oligosaccharides, which obtain from degradation of chitosan, possess
      some interesting molecular weight-dependent biological properties, especially
      anticancer activity. Therefore, the conversion of chitosan to chitosan
      oligosaccharides with specific molecular weight has been continuously
      investigated in order to find effective strategies that can achieve both economic
      feasibility and environmental concerns. In this study, a novel process was
      developed to heterogeneously degrade chitosan powder by highly active species
      generated by electrical discharge plasma in a dilute salt solution (0.02 M)
      without the addition of other chemicals. The degradation rate obtained from the
      proposed process was comparable to that obtained from some other methods with the
      addition of acids and oxidizing agents. Separation of the water-soluble degraded
      products containing chitosan oligosaccharides from the reaction solution was
      simply done by filtration. The obtained chitosan oligosaccharides were further
      evaluated for an influence of their molecular weights on cytotoxicity against
      cancer cells and the selectivity toward cancer and normal cells.

PMID- 30241812
TI  - Transglutaminase-catalyzed preparation of crosslinked carboxymethyl
      chitosan/carboxymethyl cellulose/collagen composite membrane for postsurgical
      peritoneal adhesion prevention.
AB  - Peritoneal adhesion is a general complication following pelvic and abdominal
      surgery, which may lead to chronic abdominal pain, bowel obstruction, organ
      injury, and female infertility. Biodegradable polymer membranes have been
      suggested as physical barriers to prevent peritoneum adhesion. In this work, a
      transglutaminase (TGase)-catalyzed crosslinked carboxymethyl
      chitosan/carboxymethyl cellulose/collagen (CMCS/CMCL/COL) composite anti-adhesion
      membrane with various proportions of CMCS, CMCL, and COL (40/40/20, 35/35/30,
      25/25/50) was developed. After crosslinking by TGase, the composite anti-adhesion
      membranes shown enhanced mechanical properties and improved biodegradability.
      Meanwhile, the high cytocompatibility of anti-adhesion membranes was proved by in
      vitro cell culture study. Moreover, the anti-adhesion membrane with the
      proportion of 25/25/50 was implanted between the artificially defected cecum and
      peritoneal wall in rats and following by general observation, histological
      examination, and inflammatory factors assay. The results indicated that the anti
      adhesion membrane can significantly prevent peritoneal adhesion with negligible
      immunogenicity. Therefore, the composite membrane crosslinked by TGase had
      satisfactory anti-adhesive effects with high biocompatibility and low
      antigenicity, which could be used as a preventive barrier for peritoneal
      adhesion.

PMID- 30241813
TI  - Versatile acid base sustainable solvent for fast extraction of various molecular
      weight chitin from lobster shell.
AB  - Deep eutectic solvent (DES) prepared from choline chloride and four organic acid
      were evaluated for the extraction of chitin from lobster shell. It was found that
      the purity of chitins extracted with DESs was related to acid used. Purity of
      chitin extracted with choline chloride-malonic acid was the highest. Chitins
      extracted through DES treatment results in various molecular weight, which is
      associated with type of acid and temperature used during the treatment. For
      instance, chitin produced by malonic acid at 50  degrees C and 100  degrees C
      results in molecular weight of 312 KDa and 199 KDa respectively, whereas it
      extracted with malic acid at 100  degrees C results in 91 KDa. The
      physicochemical properties of chitins were characterized by FTIR, XRD, TG and
      SEM. Moreover, the CaCO3 was successfully converted into levulinic acid calcium
      salt which could be used as calcium supplement.

PMID- 30241814
TI  - Bifunctionalized chitosan: A versatile adsorbent for removal of Cu(II) and Cr(VI)
      from aqueous solution.
AB  - This study describes the chemical modification of chitosan to produce a novel
      bifunctionalized adsorbent material (C4) for the removal of Cu2+ and oxyanions of
      Cr6+ from a single aqueous solution. The chemical modifications allowed C4 to be
      insoluble under acidic conditions, improving the chemical properties of the
      modified chitosan in aqueous solution. C4 adsorbent was synthesized by reaction
      of the amino group of chitosan with 2-pyridinecarboxaldehyde, a reduction of
      imine group, followed by esterification with EDTA dianhydride (EDTAD). C4 was
      characterized by solid-state 13C nuclear magnetic resonance, infrared
      spectroscopy, and elemental analysis. The adsorption studies of Cu2+ and
      oxyanions of Cr6+ in a batch mode were evaluated as a function of the contact
      time (kinetics), solution pH, and initial metal ion concentration. The maximum
      adsorption capacities (Qmax) of C4 for the adsorption of Cu2+ (pH 5.5) and Cr6+
      (pH 2.0) were 2.60 and 3.50 mmol/g, respectively. The reusability of the
      recovered C4 adsorbent was also evaluated.

PMID- 30241815
TI  - Conductive bacterial cellulose/multiwall carbon nanotubes nanocomposite aerogel
      as a potentially flexible lightweight strain sensor.
AB  - In this work, in-situ biosynthesized bacterial cellulose (BC) /multiwall carbon
      nanotubes (MWCNTs) nanocomposite hydrogels converted to the conductive
      nanocomposite aerogels via the supercritical CO2 method. A low percolation
      threshold value of 0.0041 (volume concentration) predicted for BC/MWCNTs
      nanocomposite aerogels by the proposed modified model. The piezoresistive
      behavior of the nanocomposite aerogel at percolation threshold, evaluated in
      tension mode. The strain sensing outcomes revealed a linear trend during loading
      until a critical strain, afterward began to decline with further increasing of
      strain. Moreover, by applying loading unloading cyclic tension for 10 times at
      two different strain amplitudes (2% and 8%), the variation of relative resistance
      was different. This attributed to the rearrangement of MWCNTs at high strain
      condition. The gauge factor of 21 and response time of 390 ms obtained for
      flexible lightweight strain sensor. The fabricated strain sensor utilized to
      monitor human detection motion.

PMID- 30241816
TI  - Development of photo and pH dual crosslinked coumarin-containing chitosan
      nanoparticles for controlled drug release.
AB  - A new strategy has been developed to the fabrication of chitosan nanoparticles as
      anticancer drug nanocarriers with ultraviolet-responsive coumarin derivatives and
      pH-responsive imine groups. For this purpose 8-formyl-7-hydroxy-4-methylcoumarin
      (8-FHMC) was initially synthesized as novel and dual crosslinking agent in order
      to produce coumarin-containing chitosan nanoparticles via oil-in-water
      nanoemulsion system. The structure of the resultant compounds and nanoparticles
      were confirmed by means of 1H NMR, FT-IR, UV-vis spectroscopy and XRD. The
      morphology and size distribution of the coumarin-containing chitosan
      nanoparticles was also characterized using SEM, AFM and DLS. The drug-loaded
      coumarin-containing chitosan nanoparticles were stable at physiological
      conditions, and can also be disassociated by the cleavage of imine linkages in
      the crosslinking segments under acidic condition. Compared to non-photo
      crosslinked chitosan nanoparticles, photo-crosslinked chitosan nanoparticles
      displayed controllable and slower release. Thus, we have showed that chitosan
      nanoparticles crosslinked by coumarin with photo- and pH-responsive properties is
      a promising and novel drug carrier for designing intelligent drug delivery
      systems.

PMID- 30241818
TI  - Highly adsorptive oxidized starch nanoparticles for efficient urea removal.
AB  - Portable dialysis is a need to implement daily and nocturnal hemodialysis. To
      realize portable dialysis, a dialysate regeneration system comprising superior
      adsorbents is required to regenerate the used dialysate. This study aims to
      develop a nano-adsorbent, derived from corn starch for urea removal. Oxidized
      starch nanoparticles (oxy-SNPs) were prepared via liquid phase oxidation,
      followed by chemical dissolution and non-solvent precipitation. The oxy-SNPs
      possessed Z-average size of 177.7 nm with carbonyl and carboxyl contents of 0.068
      and 0.048 per 100 glucose units, respectively. The urea adsorption achieved the
      equilibrium after 4 h with 95% removal. The adsorption mechanism fitted Langmuir
      isotherm while the adsorption kinetics obeyed pseudo-second-order model. This new
      material has a maximum adsorption capacity of 185.2 mg/g with a rate constant of
      0.04 g/mg.h. Moreover, the oxy-SNPs exhibited the urea uptake recovery of 91.6%.
      Oxy-SNPs can become a promising adsorbent for dialysate regeneration system to
      remove urea.

PMID- 30241817
TI  - Ionic-crosslinked polysaccharide/PEI/DNA nanoparticles for stabilized gene
      delivery.
AB  - In gene therapy, the stability of gene delivery system is essential during the
      systemic circulation. To improve the stability of PEI/DNA complexes, sodium
      alginate (Alg) was chosen as the optimal shielding material from four different
      polysaccharides. Then Alg/PEI/DNA complexes were further crosslinked by calcium
      ions (Ca2+) to form Ca2+/(Alg/PEI/DNA) nanoparticles. Compared to PEI/DNA
      complexes and Alg/PEI/DNA complexes, Ca2+/(Alg/PEI/DNA) nanoparticles exhibited
      enhanced stability, which was confirmed by the in vitro and in vivo evaluations.
      Furthermore, the pharmacokinetic study indicated that Ca2+/(Alg/PEI/DNA)
      nanoparticles exhibited longer circulation time in blood, which would be
      beneficial to the enhanced permeability and retention (EPR) effect of
      nanoparticles and could realize improved nanoparticles accumulation at tumor
      site. Overall, the Ca2+/(Alg/PEI/DNA) nanoparticles based on alginate shielding
      and Ca2+ crosslinking might be a promising platform in gene delivery and tumor
      treatment.

PMID- 30241819
TI  - Review on recent progress in chitosan-based hydrogels for wastewater treatment
      application.
AB  - Recently, chitosan has been used as a raw material for synthesis of hydrogels in
      a wide range of potential and practical applications like wastewater treatment,
      drug delivery, and tissue engineering. This review represents an overview of the
      application of chitosan-based hydrogels for wastewater treatment and helps
      researchers to better understand the potential of these adsorbents for wastewater
      treatment. It covers recently used and prospected methods for synthesis and
      modification of these hydrogels. Chitosan-based hydrogels are modified physically
      and chemically through crosslinking, grafting, impregnation, incorporating of
      hard fillers, blending, interpenetrating, and ion-imprinting methods to improve
      adsorption and mechanical properties. Understanding of these methods provides
      useful information in the design of efficient chitosan-based hydrogels and the
      select of appropriate pollutants for removal. This review provides a brief
      outlook on future prospects of chitosan-based hydrogels for wastewater
      application.

PMID- 30241820
TI  - Antineoplastic effect of pectic polysaccharides from green sweet pepper (Capsicum
      annuum) on mammary tumor cells in vivo and in vitro.
AB  - The present study investigated the antineoplastic effects of pectic
      polysaccharides that were extracted from green sweet pepper (Capsicum annuum
      [CAP]) in the Ehrlich carcinoma in mice and in human mammary tumor lineages.
      After the subcutaneous inoculation of 2 * 106 Ehrlich tumor cells, Female Swiss
      mice received 50, 100, or 150 mg/kg CAP or vehicle orally once daily or
      methotrexate (2.5 mg/kg, i.p., every 5 days) for 21 days. CAP dose-dependently
      reduced Ehrlich tumor growth. It also reduced the viability of MCF-7, MDA-MB-231,
      and MDA-MB-436 human mammary cell lineages. Treatment with CAP reduced the gene
      expression of vascular endothelial growth factor in vivo and in vitro, reduced
      vessel areas of the tumors, and induced necrosis in Ehrlich solid tumors. CAP
      treatment significantly increased Interleukin-6 in tumors. The antineoplastic
      effect of CAP appears to depend on the regulation of inflammation and
      angiogenesis. Further studies are encouraged to better understand the CAP
      potential for the treatment of breast tumors.

PMID- 30241821
TI  - Zymomonas mobilis exopolysaccharide structure and role in high ethanol tolerance.
AB  - Bacterial cell surface exopolysaccharides (EPS) provide a protective barrier from
      the external milieu and participate in host-environment interactions. Zymomonas
      mobilis, an ethanologenic Gram negative bacterium, is used by the industry in bio
      ethanol production process, due to its extraordinary resistance to a highly
      ethanolic environment. We found that Z. mobilis produces a mixture of two EPSs,
      an [alpha-(1->6)-D-Manp] mannose homopolymer and a galactose containing
      polysaccharide: [->2)-beta-D-Galf-(1->3)-beta-D-Galp-(1->]n. A physico-chemical
      study, conducted with diffusion-ordered spectroscopy (DOSY) and Dynamic Light
      Scattering (DLS), allowed to demonstrate that, differently from the majority of
      polysaccharides, ethanol is a good solvent for the galactose containing EPS,
      revealing that its chemical structure is specifically connected with the
      Zymomonas mobilis high ethanol tolerance.

PMID- 30241822
TI  - Stabilization of hyaluronan-based materials by peptide conjugation and its use as
      a cell-seeded scaffold in tissue engineering.
AB  - New materials based on molecules naturally occurred in body are assumed to be
      fully biocompatible and biodegradable. In our study, we used hyaluronic acid (HA)
      modified with peptides, which meet all this criterion and could be advantageously
      used in tissue engineering. Peptides with RGD, IKVAV or SIKVAV adhesive motif
      were attached to HA-based fiber or non-woven textile through ester bond in the
      term of solid phase peptide synthesis. A linker between HA and peptide containing
      three glycine or two 6-aminohexanoyl units was applied to make peptides more
      available for cell surface receptors. Dermal fibroblasts adhered readily on this
      material, preferentially to RGD peptide with 6-aminohexanoyl linker. Contrary,
      the absence of adhesive peptide did not allow the cell attachment but maintained
      the material stability.

PMID- 30241823
TI  - Cyclosporine-loaded cross-linked inserts of sodium hyaluronan and hydroxypropyl
      beta-cyclodextrin for ocular administration.
AB  - This work aimed to develop cyclosporine ocular inserts combining sodium
      hyaluronate (HA) and hydroxypropyl-beta-cyclodextrin (HPbetaCD). Four different
      formulations, cross-linked with poly(ethylene glycol) diglycidyl ether, were
      studied to elucidate the role of the HA:HPbetaCD proportion on the physical
      characteristics and drug release patterns. The inserts (300 MUm thickness) showed
      porous surfaces, high swelling ratios (~10), and good cytocompatibility with
      fibroblasts and chorioallantoic membrane (HET-CAM test). Cyclosporine-loaded
      inserts (~0.5% w/w drug content) appeared translucent. Release tests carried out
      under continuous flow of simulated lacrimal fluid revealed a controlled release
      of cyclosporine during the first 1 h. Conversely, differences among formulations
      were evidenced when the inserts were immersed in plenty volume of fluid; inserts
      with low content in HPbetaCD released the drug faster. These later inserts also
      facilitated cyclosporine accumulation into sclera (5.6-32.7 MUgdrug/gsclera).
      Thus, cross-linked HA:HPbetaCD inserts appear as a suitable platform for peptide
      drug release to the ocular surface.

PMID- 30241824
TI  - One-step co-culture fermentation strategy to produce high-content fructo
      oligosaccharides.
AB  - An integrated process enabling the simultaneous production and purification of
      fructo-oligosaccharides (FOS) was explored. A co-culture fermentation with
      Aspergillus ibericus (used as FOS producer strain) and Saccharomyces cerevisiae
      YIL162 W (for small saccharides removal) was optimized. Inoculation conditions of
      S. cerevisiae, fermentative broth composition, temperature and pH were optimized
      by experimental design. Yeast extract concentration and temperature were the most
      significant variables affecting FOS purity. Co-culture fermentations with
      simultaneously inoculation of the strains, run under 30  degrees C, initial pH
      6.0 and 17 g L-1 yeast extract led to FOS mixtures with 97.4 +/- 0.2% (w/w)
      purity. The fermentations conducted in bioreactor, at a 0.8 vvm aeration rate,
      yielded 0.70 +/- 0.00 gFOS.ginitial GF-1 at 45 h fermentation, with a FOS content
      of 133.7 +/- 0.1 g L-1. A purity of FOS up to 93.8 +/- 0.7% (w/w) was achieved.
      The one-step fermentation proved to be efficient, economical and fast.

PMID- 30241826
TI  - Extraction of nano cellulose fibers from the banana peel and bract for production
      of acetyl and lauroyl cellulose.
AB  - The principal aim of the present study is to develop a method for the production
      of cellulose nanofibers, from the banana peel (BP) and bract (BB). It is also the
      aim of this study to produce cellulose-based biopolymers through acetyl and
      lauroyl modifications. The microwave digestion method and ball milling assisted
      ultra-sonication method was optimized for sustainable extraction of micro and
      nano cellulose fibers, respectively. The microwave digestion method was found to
      be effective in the removal of hemicellulose and lignin. Micro and nano cellulose
      fibers of BP and BB were found to contain type I cellulose structure. Thermal
      stability and crystallinity index of cellulose nanofibers were examined to be
      higher than it's native micro cellulose. Nano cellulose fibers were examined to
      be a potential source for production of acetyl and lauroyl cellulose, with a high
      degree of substitution and thermal stability. Hence, microwave digestion and ball
      milling assisted ultra-sonication method was proven to be effective in the
      extraction of nano cellulose fiber for development of cellulose-based polymers.

PMID- 30241825
TI  - Pickering emulsions stabilized nanocellulosic-based nanoparticles for coumarin
      and curcumin nanoencapsulations: In vitro release, anticancer and antimicrobial
      activities.
AB  - Coumarin and curcumin have a wide spectrum of biological and pharmacological
      activities including antioxidant, anti-inflammatory, antimicrobial and anticancer
      but hindered therapeutic applications due to low stability and poor solubility in
      water. The main objective of the current study was to overcome these drawbacks
      via improved bioavailability by nanoencapsulated emulsions. Pickering emulsion
      (PE) via oil-in-water approach were stabilized by aminated nanocellulose (ANC)
      particles through application of a full factorial optimization design for
      nanoemulsions containing different composition of oil phase with medium chain
      triglyceride (MCT) and Tween 80. The fabricated nanoemulsions and PEs with
      average particle sizes (<=150 nm) were obtained. Influencing factors such as ANC
      concentration, storage time and pH on the stability of emulsions were examined
      alongside zeta potentials. Encapsulation efficiency (EE) of coumarin and curcumin
      were determined as >90%. Release kinetic profiles for encapsulated PEs displayed
      sustained release with supposed increase bioavailability. Higher release percent
      were detected for curcumin encapsulated PE in contrast to coumarin. In vitro
      cytotoxicity evaluation for coumarin and curcumin loaded PEs were further
      investigated for anticancer and antimicrobial activities using human cell lines
      (L929 and MCF-7) and different microorganisms (Gram (+), Gram (-) and fungi),
      respectively. The results clearly demonstrated PE coumarin and curcumin as
      promising candidates to inhibit microbial growth and to prevent preferential
      killing of cancer cells compared to normal cells.

PMID- 30241827
TI  - Exploring chitosan nanoparticles as effective inhibitors of antibiotic resistant
      skin microorganisms - From in vitro to ex vitro testing.
AB  - Nowadays, nosocomial skin infections are increasingly harder to manage and
      control. In the search for new, natural compounds capable of being alternatives
      to traditional antibiotics, chitosan and its nanoparticles, have garnered
      attention. This work sought to understand the potential of chitosan NPs in the
      management of infections caused by MDR skin pathogens in planktonic and sessile
      assays. Additionally, NPs' capacity to inhibit biofilm quorum sensing and prevent
      HaCat infections was also evaluated. The results obtained showed that chitosan
      NPs had an average size and charge of 226.6 +/- 5.24 nm and +27.1 +/- 3.09 mV.
      Inhibitory and bactericidal concentrations varied between 1 and 2 mg/mL and 2-7
      mg/mL, respectively. Chitosan NPs effectively inhibited biofilm growth for all
      microorganisms and possessed strong anti-quorum sensing activity. Lastly,
      chitosan NPs proved to be effective interfere with A. baumannii's infection of
      HaCat cells, as they significantly reduced intracellular and extracellular
      bacterial counts.

PMID- 30241829
TI  - Chitosan and carboxymethyl cellulose-multilayered magnetic fluorescent systems
      for reversible protein immobilization.
AB  - Magnetic fluorescent nanoparticles (MFNPs)-based protein immobilization systems
      were successfully synthesized via a layer-by-layer (LbL) assembly approach in an
      impinging stream-rotating packed bed, which adopted chitosan containing carbon
      dots (CDs)@Fe3O4 nanoparticles (NPs) as a precursor, chitosan (CS) or
      carboxymethylcellulose (CMC) involving CDs as shells. To reveal the relationship
      between structure and efficiency of systems, the effect of self-assembly mode and
      layer number?was investigated to provide us insight into how to improve the
      design of MFNPs-based supports. Finally, an MFNPs-based protein immobilization
      system with excellent fluorescence and magnetic response, expanded specific
      surface area, and enhanced immobilization and release performance were obtained.
      Immobilization mechanism and kinetic studies were also conducted to reveal the
      rate-controlling step and the template affinity. Taken together, this study
      provides an effective strategy to synthesize bifunctional MFNPs and to adjust the
      performance, which aims for facilitating new possibilities for biomass-based
      nanomaterials used for protein immobilization.

PMID- 30241828
TI  - Preparation and renoprotective effects of carboxymethyl chitosan oligosaccharide
      on adriamycin nephropathy.
AB  - Carboxymethyl chitosan oligosaccharide (CMCOS), the hydrolytic product of
      carboxymethyl chitosan, is nontoxic, easily absorbable and good antioxidant. In
      this study, CMCOS was prepared and its properties in adriamycin nephropathy
      therapy were investigated. Our results showed that CMCOS had good curative
      effects on renal function and parenchymal injury induced by adriamycin. CMCOS
      administration significantly relieved symptoms of proteinuria, hypoalbuminemia,
      hyperlipidemia, renal hyperplasia and histological lesions in rats (P < 0.01).
      Further exploration for the underlying mechanisms indicated that CMCOS treatment
      reduced macrophage accumulation, myofibroblast transdifferentiation and podocyte
      apoptosis. CMCOS treatment could regulate secretions of cytokines (IL-1beta, TNF
      alpha and TGF-beta1) and improve activities of antioxidative enzymes (SOD, GSH
      Px) (P < 0.01). In conclusion, therapeutic effects of CMCOS on renal injury
      mediated by inflammation, fibrosis and oxidative stress made it a good kidney
      health product and a promising candidate in clinical treatment of human chronic
      kidney disease.

PMID- 30241830
TI  - Surface-modified microcrystalline cellulose for reinforcement of chitosan film.
AB  - We here report an inexpensive active filler of surface-modified microcrystalline
      cellulose (MCC) particle for reinforcement of polymer material. A commercial MCC
      powder with particle size of about 50 MUm was mixed with urea and was then
      irradiated under microwave for the modification. The obtained urea-modified MCC
      (u-MCC) was able to be dispersed in a chitosan solution without precipitation for
      over 48 h, which provided a time window for its processing. After the mixture
      slurry was cast onto glass substrate and then coagulated in a NaOH aqueous
      solution, a full natural polymer composite film has been prepared. The mechanical
      properties of the obtained composite films have been carefully measured and
      discussed. Our results indicate that the mechanical properties reach the highest
      when the urea-modified MCC is 7 wt% in the composite film: the tensile strength,
      the breaking elongation, the Young's modulus and the fracture energy are
      respectively about 2.0, 2.1, 2.4 and 6.0 times those of the pure chitosan film.
      The reinforcement of the composite material with the u-MCC particles was studied
      through scanning electron microscopy, Fourier transform infrared spectroscopy and
      X-ray diffraction analyses, and has been attributed to the strong interaction
      between the surface-modified MCC particles and the neighboring chitosan chains in
      the film matrix. Moreover, the water vapor permeability and the transparency of
      the composite films have been determined to evaluate the potential applications
      such as gas impervious material and packaging material.

PMID- 30241831
TI  - Microwave radiation and protein addition modulate hydration, pasting and gel
      rheological characteristics of rice and potato starches.
AB  - This study evaluated for first time the effect of Microwave (MW) radiation on
      systems based on potato and rice starches supplemented with 5% of calcium
      caseinate (CA) or soy protein isolate (SPI). The goal of this treatment was the
      physical modification of these starch-based systems to provide ingredients of new
      functionalities. The hydration and pasting properties as well as gel viscoelastic
      features were evaluated. Dynamic oscillatory rheological tests were used. The
      effect of MW treatment (MWT) depended on the starch botanical origin and was
      significantly affected by protein presence and type. MWT of starch + protein
      blends revealed the most notable changes when SPI was added. Adding it to rice
      starch decreased swelling power (-45%), altered viscometric profiles and
      reinforced gel structure with important increases in both viscoelastic moduli
      (+160%-G' and +58%-G''). In blends with potato starch, MWT increased water
      absorption capacity (+115%) and decreased water solubility index (-82%). MWT of
      protein-potato blends promoted gel stability, decreased their pasting profiles
      and resulted in enhanced viscoelastic moduli (+483-G' and 243%-G''). MWT combined
      with protein addition allows designing starch-based foods with tailored
      properties.

PMID- 30241832
TI  - Functional modification of cellulose fabrics with phthalocyanine derivatives and
      the UV light-induced antibacterial performance.
AB  - Cellulose fabrics were modified with a derivative of copper phthalocyanine
      (Reactive Blue C.I. 21) by dyeing method. The modified cellulose fabrics
      exhibited important photoactive property, such as the hydroxyl radicals
      generating ability. The UV-vis spectrum, exhaustion rate, fixation rate and
      grafting quantity of Reactive Blue 21 on the cellulose fabrics were measured and
      calculated. The chemical structure and morphology of the modified cellulose were
      characterized. The amount of the produced hydroxyl radicals was measured and the
      photoactive mechanism was discussed. The UV light-induced antibacterial
      performance of the modified materials was measured. The modified cellulose
      exhibited photo-induced antibacterial activity against both Staphylococcus aureus
      and Escherichia coli.

PMID- 30241833
TI  - Effects of temperature on cellulose hydrogen bonds during dissolution in ionic
      liquid.
AB  - Ionic liquids have been powerful solvents for cellulose. Mechanistic
      investigations of the dissolution processes have been extensively studied. In
      this paper, an experimental study has revealed that temperature also comes into
      play in cellulose dissolution. The supramolecular stuctrure of cellulose has been
      measured by X-ray diffraction, Fourier transform infrared spectroscopy, Solid
      state CP/MAS 13C NMR, X-ray photoelectron spectroscopy and Gel permeation
      chromatography analysis, and the effects of temperature on hydrogen bonds of
      cellulose in ILs were investigated. These results indicated that hydrogen bonds
      of cellulose might be cracked by different ways at different temperature: The
      disruption of intramolecular hydrogen bonds (O(3) H-O (5)) could promote the
      dissolution process at lower temperature. And the disruption of intramolecular
      hydrogen bonds (O(2) H-O (6)) might be responsible for cellulose dissolution at
      higher temperature. It was suggested that higher dissolving temperature might be
      a way to avoid cellulose degradation with a high cellulose yield.

PMID- 30241834
TI  - Pectin mediated synthesis of nano hydroxyapatite-decorated poly(lactic acid)
      honeycomb membranes for tissue engineering.
AB  - The fabrication of porous films with bioactive nanoparticles has been arousing
      interest in nanobiotechnology. The biocompatible nanocomposite membrane could
      mimic the functions of basement membrane besides the augmented cell functions
      including adhesion, spreading, proliferation, and differentiation. We have
      reported the green template synthesis of nano hydroxyapatite (nHAp) using pectin
      from bitter gourd fruits followed by the fabrication of nHAp (2 wt%, 4 wt%, and 6
      wt%) incorporated honeycomb-like poly(lactic acid) (PLA) films to evaluate the
      effect of nHAp on the surface patterning of PLA films. The use of naturally
      available bitter gourd with pectin content could efficiently stabilize or envelop
      the nanoparticles after nucleation process, resulting in reduced particle size.
      The cell viability over normal cells and cancer cells were evaluated for H
      PLA/nHAp films. The present work recommends the biofriendly surface engineering
      of PLA films with the assistance of nHAp particles for bone tissue engineering.

PMID- 30241835
TI  - Preparation and characterization of poly(ethylene terephthalate) films coated by
      chitosan and vermiculite nanoclay.
AB  - Chitosan (CS) layers are coated on a poly(ethylene terephthalate) (PET) film in
      order to decrease the oxygen permeability through the polymeric films for food
      packaging applications. Oxygen transmission rate (OTR) of the 130 MUm PET films
      can be decreased from 11 to only 0.31 cm3/m2.day with a coated layer of 2 MUm of
      CS. Additional decrease is obtained with the addition of vermiculite (VMT) to CS
      matrix in high proportion (40 to 50 w/w%). The OTR of the coated PET films
      decreased to very low values, below the detection limit of commercial
      instrumentation (<=0.008 cm3/m2 day). This high-barrier behavior is believed to
      be due to the brick wall nanostructure, which produces an extremely tortuous path
      for oxygen molecules.

PMID- 30241836
TI  - Effects of a dielectric barrier discharge (DBD) treatment on
      chitosan/polyethylene oxide nanofibers and their cellular interactions.
AB  - In this study, chitosan (CS)/polyethylene oxide (PEO) nanofibrous mats (O: 166 +/
      43 nm) were fabricated by electrospinning and subsequently surface-modified by a
      dielectric barrier discharge (DBD) sustained in argon, ammonia/helium or
      nitrogen. The surface properties of the CS/PEO nanofibers (NFs) before and after
      plasma treatment were characterized using contact angle measurements, X-ray
      photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM).
      Additionally, the mechanical properties and PEO leaching in aqueous conditions of
      the different NFs under study were examined by tensile tests and nuclear magnetic
      resonance (1H NMR) spectroscopy respectively. Finally, cell behavior and cell
      morphology of human foreskin fibroblasts (HFFs) on the CS/PEO NFs were evaluated
      via live/dead fluorescence microscopy, MTT assays and SEM. The obtained results
      revealed that the surface free energy of the CS/PEO NFs was significantly
      increased after plasma modification, which was correlated to an enrichment in
      surface oxygen (Ar, N2, NH3/He) and nitrogen (N2, NH3/He) functional groups. All
      performed plasma treatments also led to an increase in ultimate tensile strength,
      most likely due to an increased fiber-to-fiber friction. Additionally, it was
      also observed that N2 plasma treatment resulted in a decrease in PEO release,
      which could be attributed to more pronounced surface cross-linking. Cellular
      interactions on the CS/PEO NFs also significantly increased due to the performed
      plasma treatments. The best cellular response was noted for the Ar plasma
      modification although the surface hydrophilicity was the lowest in this case.
      These observations thus suggest that not only the wettability characteristics but
      also the presence of distinct functional groups on plasma-treated CS/PEO NFs have
      a significant influence on the observed enhanced cellular interactions.

PMID- 30241837
TI  - Pickering emulsifiers based on hydrophobically modified small granular starches
      Part II - Effects of modification on emulsifying capacity.
AB  - Small granular starches from rice, quinoa, and amaranth were modified with
      octenyl succinic anhydride (OSA) at 5 defined intervals (0-3.0%) and investigated
      with respect to emulsifying capacity and stability. Starch granule surfaces were
      characterized by Brunauer-Emmett-Teller and contact angle measurements.
      Emulsifying capacity was characterized by multiple light scattering (MLS) and
      particle size analysis. Stability towards environmental stress was characterized
      by centrifugation and MLS. Surface hydrophobicity and emulsifying capacity
      correlated with starch type and modification level. Quinoa stabilized emulsions
      had the smallest droplet size (e.g. 59.2 MUm at 3.0% OSA) and superior stability,
      both before and after centrifugation, especially at the lowest modification
      levels. Rice and amaranth had larger droplets (99.8 and 84.1 MUm at 3.0% OSA
      respectively). Amaranth, despite its small size showed poorer performance than
      quinoa, especially at lower modification levels. The higher emulsifying
      efficiency of quinoa starch granules attributed to the higher protein content.

PMID- 30241838
TI  - Electrosprayed chitosan microcapsules as delivery vehicles for vaginal
      phytoformulations.
AB  - The design of novel delivery systems to treat vaginal fungal infections is a
      topic of high interest. Chitosan, being itself antimicrobial and having good
      mucoadhesive properties, is an excellent candidate as a delivery matrix for
      active compounds. In this work, chitosan microcapsules containing dry extracts of
      Argentinean medicinal plants with proved biological properties (Larrea
      divaricata, L. cuneifolia, L. nitida, Zuccagnia punctata and Tetraglochin andina)
      were developed through electrospraying and compared with conventionally used
      tablets containing the same extracts. Total phenolics, loading efficacy, physical
      properties, morphology and particle size, molecular organization, water sorption
      capacity, release of bioactive compounds and biological properties were assessed.
      The encapsulation process or the inclusion in tablets did not degrade the
      bioactive compounds of the extracts. The release of phenolic compounds from
      chitosan microcapsules was faster than from tablets. The fingerprint of released
      phenolic compounds from microcapsules and tablets was similar to that from the
      dry extracts and the antioxidant and antifungal capacity remained unchanged. The
      FT-IR analysis suggested interactions between the chitosan and the extracts,
      which explained why the microcapsules kept the integrity in slightly acidic
      media. Increased solubility of the extracts when incorporated in the
      microcapsules was seen in simulated vaginal fluid, potentially increasing the
      bioavailability of bioactive compounds in the vaginal environment. This work
      highlights the potential of the chitosan-based delivery systems for
      phytomedicines with antifungal and antioxidant activity to be used in
      vulvovaginal candidiasis.

PMID- 30241839
TI  - Straightforward one-step solvent-free synthesis of the flame retardant for cotton
      with excellent efficiency and durability.
AB  - A flame retardant, ammonium salt of 1-hydroxyethylidene-1,1-diphosphonic acid
      (AHEDPA), was synthesized by a facile one-step methodology and was proven to have
      achieved remarkable improved flame retardancy of cotton with exceptional
      durability because AHEDPA with functional groups PO-(NH4+)2 could react with OH
      of cellulose to form new POC bonds characterized by Fourier transform infrared
      (FT-IR) spectra, which further verify that AHEDPA was chemically bound to cotton
      instead of as additive or mixing into polymer. Combustion behaviors of the
      control and treated cotton were assessed by cone calorimetry, vertical
      flammability and limiting oxygen index (LOI) tests. The cone calorimetry results
      display that the peak heat release rate (PHRR) and total heat release (THR) of
      cotton fabric treated by 30% AHEDPA were reduced up to 95% and 68%, respectively,
      compared with those of control cotton. No after-flame and after-glow phenomena
      for treated cotton were observed in vertical flammable test. LOI test evinces
      that the cotton fabric treated with 30-40 % AHEDPA could be used as a durable
      flame retardant fabric with a LOI value of 26.2-29.5% after 50 laundering cycles.
      Thermogravimetric (TG) data both in nitrogen and in air atmosphere reveal that
      the AHEDPA treated cotton notably increased the char yield by catalyzing
      dehydration of cellulose, thus protecting the underlying matrix from heat and
      fuel. The efficient and durable flame retardant for the AHEDPA by the one-step
      synthesis method has great development prospects in industrial.

PMID- 30241840
TI  - Highly stretchable and transparent films based on cellulose.
AB  - Developing natural products to replace synthetic plastics is necessary due to the
      serious environmental problem of non-biodegradable plastic waste. Cellulose is
      the most abundant natural material that is from all plants. This paper reports
      our success in achieving the most stretchable and transparent cellulose-based
      films through a very green process. The films are highly transparent, with 90%
      transparency per 100 MUm at 550 nm wavelength. The films are very flexible, able
      to be twisted and folded greatly without breaking. The film can reach an
      unprecedented maximum of 233% elongation at break. The success in such highly
      stretchable and transparent films sheds light on the great promise of cellulose
      for potential applications to replace synthetic plastics, such as transparent and
      stretchable substrates for flexible and stretchable electronics, transparent and
      stretchable films and various products. The mechanisms in achieving high
      transparency, flexibility and stretchability of the cellulose-based films are
      discussed.

PMID- 30241841
TI  - Beta-Glucan based temperature responsive hydrogels for 5-ASA delivery.
AB  - A series of temperature responsive hydrogels consisting of (1,3)-(1,6) beta
      Glucan and poly (N-isopropyl acrylamide) (PNIPAM) was synthesized by redox
      polymerization at room temperature. Tetramethylethylenediamine (TEMED) and
      potassium persulfate (KPS) were used as a redox pair. beta-glucan was
      methacrylated (MA-beta-Glucan) and used as a biodegradable and bio-compatible
      cross-linker to prepare beta-glucan-PNIPAM based temperature responsive
      hydrogels. Swelling behavior of the hydrogels at different temperatures was
      investigated. The 5-ASA release from the hydrogels was monitored using UV-VIS
      spectrophotometer at 37  degrees C. It is notable that, the swelling and release
      behaviors of the hydrogels significantly change depending on the hydrogel
      compositions and temperature. Their thermal stability was determined using
      thermogravimetric analysis (TGA), assuming the extent of intermolecular
      interaction between PNIPAM and beta-glucan is proportional to thermal stability,
      which increased with the amount of PNIPAM. Volume phase transition temperature
      (VPTT) of the hydrogels was precisely determined by derivative differential
      scanning calorimeter (DDSC). They possessed variable VPTT with the compositions.
      The presence of beta-glucan in the PNIPAM network brought VPTT closer to the body
      temperature (from 32.8  degrees C to 35.5  degrees C), indicating that the VPTT
      could be tuned by the hydrogel compositions. Their in-vivo biocompatibility was
      tested against WS1 human fibroblast cells in phosphate buffer saline (PBS, pH
      7.4). It was demonstrated that, using MA-beta-glucan as a cross-linker resulted
      in more bio-compatible thermo-responsive hydrogels indicating the enhancement of
      hydrophilic beta-Glucan on the swollen hydrogel surface.

PMID- 30241842
TI  - UV-induced self-cleanable TiO2/nanocellulose membrane for selective separation of
      oil/water emulsion.
AB  - Emulsified oily wastewater threated to human health seriously, and traditional
      technologies are unable to separate the emulsion for the small size of oil
      droplets. Membranes with special wettability are considered as an efficient way
      for oil/water emulsions separation, but challenges remain in terms of high
      material costs, complex processing, and easy to be fouled. Herein, novel self
      cleanable membranes composed of nanocellulose and TiO2 nanoparticles were
      developed through a facile and sustainable vacuum-assisted filtration process.
      TiO2 nanoparticles in situ generated on the surface of tunicate cellulose
      nanocrystals (TCNC), a kind of nanocellulose, by hydrolysis of titanium
      oxysulfate. The prepared nanocomposite membrane showed hierarchical architecture,
      high roughness, superhydrophilicity and underwater oleophobicity. After UV-light
      irradiation, the resulting membrane exhibited improved underwater oil contact
      angles and water fluxes, beneficial for the selective oil/water emulsions
      separation. Importantly, the TiO2/nanocellulose membrane could rapidly degrade
      contaminant (oleic acid) under UV-light irradiation, suggesting excellent self
      cleaning property. This works provided a facile strategy for development of self
      cleanable membrane from nanocellulose for oil/water emulsion separation.

PMID- 30241843
TI  - Rheological characterization of new thermosensitive hydrogels formed by chitosan,
      glycerophosphate, and phosphorylated beta-cyclodextrin.
AB  - A novel thermosensitive hydrogel consisting of phosphorylated beta-cyclodextrin
      (betaCD-PH), beta-cyclodextrin (betaCD) and chitosan was prepared by embedding
      betaCD and betaCD-PH, into the well-studied chitosan/alphabeta-glycerophosphate
      system (CS/alphabetaGP). The relevance of this work is the use of betaCD-PH to
      partially substitute alphabetaGP as the gelling agent. The role of betaCD and
      betaCD-PH on the rheological properties of hydrogels, gelation time, and gelation
      temperature were investigated. The gelation time for all the samples
      (CS/alphabetaGP, CS/alphabetaGP/betaCD, and CS/alphabetaGP/betaCD-PH) was less
      than a minute at 37  degrees C, which is suitable for biomedical applications.
      The gelation temperature for hydrogel CS/alphabetaGP/betaCD-PH increased linearly
      with the addition of betaCD-PH within the interval 31.8-37.3  degrees C, at
      ratios CS:betaCD-PH of 1:0.5, 1:1, 1:1.5 and 1:2 (w/w). The hydrogel thus
      obtained has potential applications in dual drug delivery (hydrophilic and
      hydrophobic).

PMID- 30241844
TI  - Preparation of conductive cellulose paper through electrochemical exfoliation of
      graphite: The role of anionic surfactant ionic liquids as exfoliating and
      stabilizing agents.
AB  - A facile electrochemical exfoliation method was established to efficiently
      prepare conductive paper containing reduced graphene oxide (RGO) with the help of
      single chain anionic surfactant ionic liquids (SAILs). The surfactant ionic
      liquids are synthesized from conventional organic surfactant anions and a 1-butyl
      3-methyl-imidazolium cation. For the first time the combination of SAILs and
      cellulose was used to directly exfoliate graphite. The ionic liquid 1-butyl-3
      methyl-imidazolium dodecylbenzenesulfonate (BMIM-DBS) was shown to have notable
      affinity for graphene, demonstrating improved electrical properties of the
      conductive cellulose paper. The presence of BMIM-DBS in the system promotes five
      orders of magnitude enhancement of the paper electrical conductivity (2.71 * 10-5
      S cm-1) compared to the native cellulose (1.97 * 10-10 S cm-1). A thorough
      investigation using electron microscopy and Raman spectroscopy highlights the
      presence of uniform graphene incorporated inside the matrices. Studies into
      aqueous aggregation behavior using small-angle neutron scattering (SANS) point to
      the ability of this compound to act as a bridge between graphene and cellulose,
      and is responsible for the enhanced exfoliation level and stabilization of the
      resulting dispersion. The simple and feasible process for producing conductive
      paper described here is attractive for the possibility of scaling-up this
      technique for mass production of conductive composites containing graphene or
      other layered materials.

PMID- 30241845
TI  - Nanoparticles capture on cellulose nanofiber depth filters.
AB  - A self-standing filter with a porosity of 80% is prepared from naturally abundant
      cellulose biopolymer in its native state by water-based cationization and freeze
      drying processes. The positive surface charge of the filter in a wide pH range
      favors its interaction with various nanoparticles (NPs), while its tortuous sheet
      structure builds a contact between cellulose nanofibers (CNF) and the NPs, and
      hinders them to pass through the filter. Unlike membranes used for the retention
      of NPs and viruses, the separation in the CNF filter is not only limited to its
      surface but occurs also in its interior even when the NPs are orders of magnitude
      smaller than the filter pores. Additional functionalities added to the filter
      enlarge the spectrum of NPs it can separate. NPs supported onto the filter can
      thereafter be utilized for the reduction of harmful chemicals into their benign
      form. The present filter concept may not only address shortcomings of the current
      membrane systems, but could offer a disruptive technology for the sustainable and
      universal water purification.

PMID- 30241846
TI  - Spruce xylan/HEMA-SBA15 hybrid hydrogels as a potential scaffold for fibroblast
      growth and attachment.
AB  - A hybrid hydrogel (GHC-SBA15) based on spruce xylan (HC), 2-hydroxyethyl
      methacrylate (HEMA), and mesoporous silica (SBA15) was prepared with the intended
      use of fibroblast attachment and growth. Xylan was functionalized with acryloyl
      chloride to introduce vinyl groups and was crosslinked by radical polymerization
      with HEMA in presence of SBA15. Infrared spectroscopy and nuclear magnetic
      resonance confirmed the copolymerization of HEMA with xylan. Up to 20 wt.%
      addition, SBA15 was homogenously incorporated in the structured hydrogel network
      as observed by SEM. Moreover, nitrogen adsorption-desorption, small angle X-ray
      scattering and transmission electron microscopy indicated that the mesoporous
      SBA15 framework was maintained and that the hybrid hydrogel was a physical
      mixture of SBA15 with the copolymer HC/HEMA. Rheological analysis revealed that
      addition of 20% w/w SBA15 into hydrogel enhanced significantly the mechanical
      properties. In addition, we demonstrate that fibroblast L929 cells grew and
      spread on GHC-SBA15. Cell viability was within the expected range.

PMID- 30241847
TI  - Structural elucidation and immune-enhancing activity of peculiar polysaccharides
      fractioned from marine clam Meretrix meretrix (Linnaeus).
AB  - The marine clam Meretrix meretrix was subjected to extraction with a combined
      procedure of water decoction, ethanol precipitation, and deproteinization to
      yield a water-soluble polysaccharide coded as MMP. The product was fractionated
      with DEAE-52 cellulose and resulted in two soluble fractions designated as MMP-2
      and -3. The structures of the fractions were determined by chemical and
      physicochemical analysis, and their immunomodulation activities and cytokine
      production were assayed by lymphopoiesis. Results showed that MMP-2 and -3 were
      glucomannan and glucogalactan homologs, respectively. They possess average
      molecular masses of 272 and 257 kDa, respectively, and were elucidated as
      branched copolymers, elaborated as alpha(1->4)-glucan branching with mannose or
      galactose via beta(1->6)-linkage. Bioassay indicated that MMP-2 and -3 held
      moderate potentials in restoring immune function because they augment splenocyte
      proliferation and enhance the cytokine secretion of lymphocytes dose-dependently.
      We speculated that their bioactivities are closely correlated with their peculiar
      structures.

PMID- 30241848
TI  - Degradation of carboxymethylcellulose using ultrasound and beta-glucanase:
      Pathways, kinetics and hydrolysates' properties.
AB  - In order to provide an efficient way to degrade carboxymethylcellulose (CMC),
      three pathways were investigated: enzymolysis, combination of ultrasound
      pretreatment and enzymolysis, and sonoenzymolysis. Effects of these treatments on
      enzymatic kinetics, degradation kinetics and properties of degraded CMC were
      investigated. The degradation degree of CMC was increased by 18.90% and 35.73%
      with ultrasound pretreatment (at an intensity of 24 W/mL for 30 min) and
      sonoenzymolysis (at an intensity of 9 W/mL for 50 min), compared with that
      obtained under the traditional enzymolysis. Analysis of kinetics demonstrated
      that ultrasound, both pretreatment and combined with beta-glucanase, could
      accelerate CMC degradation. Measurements of rheological properties, molecular
      weight and structures of CMC hydrolysates revealed that ultrasound broke the
      glycosidic bond of CMC chains without changing its primary structure. The
      sonoenzymolysis process was the most efficient method to degrade CMC, with
      potential to provide a way to obtain CMC with lowest molecular weight or
      viscosity.

PMID- 30241849
TI  - An injectable self-healing hydrogel with adhesive and antibacterial properties
      effectively promotes wound healing.
AB  - Hydrogels with self-healing capacity can undergo self-repair, establishing safer
      and longer-lasting products. Hydrogel wound dressings showing self-healing
      capacity can prolong the lifespan of the material and provide better wound
      protection. Therefore, in this study, Schiff base reactions (reversible imine
      linkages) were utilized to design injectable self-healing hydrogels with chitosan
      and konjac glucomannan. Oxidized konjac glucomannan was used to react with
      chitosan to form hydrogel. In addition to injectable, self-healing properties,
      the hydrogels also had adhesive and antibacterial properties, were biocompatible,
      and promoted wound healing. The inhibition rates of hydrogels against
      Staphylococcus aureus and Escherichia coli were 96% and 98%, respectively. In
      addition, microscopy and rheological analyses showed that the hydrogels healed
      within 4 h without additional exogenous stimulation. Finally, the developed
      hydrogels were injectable and significantly shortened wound recovery time in a
      full-thickness skin defect model. Thus, our findings established a novel hydrogel
      material that may have applications in wound healing.

PMID- 30241850
TI  - Inhibition of Leishmania amazonensis arginase by fucogalactan isolated from
      Agrocybe aegerita mushroom.
AB  - The inhibition of arginase from Leishmania spp. is considered a promising
      approach to the leishmaniasis treatment. In this study, the potential of a
      fucogalactan isolated from the medicinal mushroom Agrocybe aegerita was evaluated
      against arginase (ARG) from Leishmania amazonensis. The polysaccharide was
      obtained via aqueous extraction, and purified by freeze thawing and precipitation
      with Fehling solution. Its chemical structure was established by monosaccharide
      composition, methylation analysis, partial acid hydrolysis, and NMR spectroscopy.
      The data indicated that it is a fucogalactan (FG-Aa; Mw = 13.8 kDa), having a (1
      >6)-linked alpha-D-Galp main-chain partially substituted in O-2 by non-reducing
      end-units of alpha-L-Fucp. FG-Aa showed significant inhibitory activity on ARG
      with IC50potency of 5.82 +/- 0.57 MUM. The mechanism of ARG inhibition by the
      heterogalactan was the competitive type, with Kiof 1.54 +/- 0.15 MUM. This is the
      first report of an inhibitory activity of arginase from L. amazonensis by
      biopolymers, which encourages us to investigate further polysaccharides as a new
      class of ARG inhibitors.

PMID- 30241851
TI  - Development of effective nano-biosorbent based on poly m-phenylenediamine grafted
      dextrin for removal of Pb (II) and methylene blue from water.
AB  - Novel nano-biosorbent was successfully prepared based on dextrin-g-poly m
      phenylenediamine (DgPmPDA) and graphene oxide (GO) by using the solution blending
      technique and was found to be an effective adsorbent for Pb(II) and methylene
      blue (MB) dye. The nano-biosorbent was characterized by FTIR, CHN, XRD, SEM, AFM
      and TGA. The adsorption process depended on the pH of solution, adsorbent dosage,
      contact time, initial concentration of Pb(II) and MB, and temperature.
      Experimental results were in good agreement with Langmuir isotherm model for both
      Pb(II) and MB adsorption. The maximum adsorption capacity (Qmax) of Pb(II) and MB
      was found to be 80 mg/g and 76.33 mg/g, respectively, at optimum conditions.
      Results showed that the kinetics of Pb(II) and MB onto the DgPmPDA@GO nano
      biosorbent followed the pseudo-first-order and pseudo-second-order models,
      respectively. Thermodynamic parameters exhibited the endothermic and spontaneous
      nature of the sorption process. A possible mechanism of adsorption was suggested
      where pi-pi stacking interactions, H-bonding interaction and electrostatic
      attraction controlled the MB adsorption and chelation and electrostatic
      attraction controlled the Pb(II) adsorption.

PMID- 30241852
TI  - Effect of structure features of polysaccharides on properties of dialdehyde
      polysaccharide tanning agent.
AB  - Sodium alginate (SA), tara gum (TG), starch (ST) and cyclodextrin (CD) were
      oxidized to dialdehyde polysaccharides (DAPs) using equivalent sodium periodate.
      The effects of polysaccharide structure features on aldehyde group content,
      molecular size and tanning performance of DAPs were investigated. Each DAP had
      abundant aldehyde groups (>7 mmol/g) for fur tanning in the experimental
      conditions, and DAP with higher aldehyde group content was obtained when
      polysaccharide with lower molecular weight and linear chain was used. Lower
      crystallinity and beta-(1->4) glycosidic linkage of polysaccharide benefited its
      degradation. Compared with dialdehyde ST (Mw>150,000) and dialdehyde CD (Mw<500),
      DAPs prepared from beta-(1->4)-linked amorphous SA and TG had moderate molecular
      sizes (Mw 15,000-30,000) and exhibited satisfactory penetrability and
      crosslinking reactivity in collagen fiber network, and thus performed more
      favorable tanning properties in terms of higher shrinkage temperature and
      whiteness of fur. This suggests the suitability of beta-(1->4)-linked amorphous
      polysaccharides for preparing dialdehyde tanning agents.

PMID- 30241853
TI  - A heteropolysaccharide from Saccharina japonica with immunomodulatory effect on
      RAW 264.7 cells.
AB  - A heteropolysaccharide (SHP) with a strong immunomodulatory effect on RAW 264.7
      cells was prepared from Saccharina japonica. Chemical analysis demonstrated that
      SHP was primarily composed of mannose, glucuronic acid, glucose, fucose,
      galactose, xylose and rahmnose with a molar ratio of
      1.00:0.85:0.84:0.58:0.30:0.37:0.15. ESI-MS showed that depolymerized SHP produced
      oligo-glucuronan, oligo-glucuronomannan, sulfated fuco-oligosaccharides and other
      hetero-oligosaccharides. The in vitro immunomodulatory results showed that SHP
      could increase NO production and up-regulate the expression of many immune
      effectors, including iNOS, COX-2 and TNF-alpha, displaying an apparent immune
      enhancement activities. Western blot analysis proved that SHP activated the
      expression levels of many key components involved in NF-kappaB, MAPK and Akt
      signaling pathways. Our results together indicated that SHP has the potential to
      be developed as a novel immunomodulator for activating immune system.

PMID- 30241854
TI  - Characterization, antioxidant and antiinflammation of mycelia selenium
      polysaccharides from Hypsizygus marmoreus SK-03.
AB  - The synergistical action of inflammation response with oxidative stress has been
      reported to be response for the pathogenesis of lipopolysaccharide (LPS)-induced
      lung damage. In our present work, the antioxidative and anti-inflammatory
      efficacies of mycelia selenium polysaccharides (MSPS) from Hypsizigus marmoreus
      SK-03 in LPS-induced lung damaged mice, and its structure characterizations had
      been evaluated and analyzed. The animal investigations indicated that MSPS
      markedly ameliorated pulmonary injuries by the regulations of related
      inflammatory events via the observably antioxidant effects at the dose of 800
      mg/kg. The characterizations showed that MSPS was a alpha- and beta
      configurational semi-crystalline polymer with small molecular weights, and
      expressed an integrated surface and regular shapes with homogeneous particles.
      Taken together, the current work demonstrated that MSPS might be a potentially
      effective candidate medicine for the treatment of lung damage and its
      complications.

PMID- 30241855
TI  - Extracellular depolymerisation triggers fermentation of tamarind xyloglucan and
      wheat arabinoxylan by a porcine faecal inoculum.
AB  - Arabinoxylan (AX) and xyloglucan (XG) are important components of primary cell
      walls of cereal grains and vegetables/fruits, respectively. Despite the
      established health benefits of these non-starch polysaccharides, the mechanisms
      of their utilisation by the gut microbiota are poorly understood. In this study,
      the mechanisms of solubilised wheat AX and tamarind XG degradation were
      investigated under in vitro fermentation conditions using a porcine faecal
      inoculum. Through structural analysis of the polymers, we demonstrate that
      depolymerisation by microbial surface accessible endo-degrading enzymes occurs
      prior to active fermentation of AX or XG. Breakdown products are released into
      the medium and potentially utilised cooperatively by other microbes. Acetate and
      propionate are the main fermentation products and are produced concurrently with
      polysaccharide depletion. Butyrate, however, is produced more slowly consistent
      with it being a secondary metabolite.

PMID- 30241856
TI  - One-pot fabrication of pH/reduction dual-stimuli responsive chitosan-based
      supramolecular nanogels for leakage-free tumor-specific DOX delivery with
      enhanced anti-cancer efficacy.
AB  - Facile one-pot approach was established to fabricate chitosan-based
      supramolecular nanogels as pH/reduction dual-stimuli responsive drug delivery
      system (DDS) for anticancer drug (doxorubicin, DOX), by bioreducible crosslinking
      of the beta-cyclodextrin modified chitosan (CD-CS) with disulfide bond embedded
      crosslinker (Ad-SS-Ad) via host-guest inclusion and simultaneous DOX loading. The
      DOX@Ad-SS-Ad/CD-CS supramolecular nanogels with hydrodynamic diameter (Dh) of 140
      nm and drug-loading capacity of 15.9% were obtained with the mass feeding ratio
      of carrier:DOX at 25:10. They were stable in the simulated physiological medium
      with premature drug release of only 3% over 60 h, while a high cumulative release
      up to 82.3% was achieved within 84 h in a sustained manner without initial burst
      in the simulated tumor intracellular micro-environment. The MTT assays indicated
      that the blank Ad-SS-Ad/CD-CS supramolecular nanogels were cytocompatible, while
      the proposed DOX@Ad-SS-Ad/CD-CS supramolecular nanogels possessed the enhanced
      antitumor efficacy in comparison with the free DOX.

PMID- 30241857
TI  - Tough, sticky and remoldable hydrophobic association hydrogel regulated by
      polysaccharide and sodium dodecyl sulfate as emulsifiers.
AB  - Hydrophobic association hydrogels have been extensively studied during the past
      decades. However, the fracture stress of hydrophobic association hydrogels
      obtained with anionic surfactants (such as sodium dodecyl sulfate) achieved
      hundreds of Pascal. In this investigation, combined surfactants consisting of
      polysaccharide (gum arabic) and sodium dodecyl sulfate were utilized to stabilize
      hydrogels with high fracture stress of more than 1 MPa. Moreover, the hydrogels
      exhibited excellent self-healing capacity and remoldable behavior without any
      stimulation. Simultaneously, the hydrogels demonstrated an adhesive behavior for
      various solid substrates including polytetrafluoroethylene, plastics, rubbers,
      glasses, metals and woods. The hydrogel with toughness, self-healing, stickiness
      and remoldable properties would be expected to be applied in the medical fields,
      such as wound dressing, medical electrodes, tissue adhesives and portable
      equipment.

PMID- 30241858
TI  - Effect of molecular weight of hyaluronan on zein-based nanoparticles:
      Fabrication, structural characterization and delivery of curcumin.
AB  - Zein and hyaluronan with different molecular weights (hyaluronic acid, HA and
      sodium hyaluronate, SHA: 100, 1000, and 2000 kDa) were used to fabricate the zein
      hyaluronan (ZH) nanoparticles by the antisolvent coprecipitation method. With
      increasing molecular weight of hyaluronan, the particle size, zeta-potential, and
      turbidity were gradually increased. Zeta-potential and Fourier transform infrared
      spectroscopy (FTIR) results indicated that electrostatic attraction was the
      dominant driving force, followed by hydrogen bonding and hydrophobic effects.
      Circular dichroism and fluorescence spectroscopy results revealed that the
      secondary structure was changed in zein after its combination with hyaluronan.
      The uniform spherical zein-HA (100 kDa) nanoparticles (size, 186.4 nm) was
      designed as a new delivery vehicle for curcumin with the high encapsulation
      efficiency (95.03%) and loading capacity (3.66%), and curcumin exhibited a better
      stability of anti- light degradation, and control release in simulate
      gastrointestinal digestion. This work would have a contribution to the
      development of novel delivery systems.

PMID- 30241859
TI  - Contrasting effects of albumin and hydroxyethyl starch solutions on physical
      properties of sodium hyaluronate solution.
AB  - Hydroxyethyl starch (HES) solution reportedly sheds the endothelial surface layer
      (ESL) consisting of polysaccharide glycosaminoglycans, whereas albumin stabilizes
      the ESL. Here we compared the effects of albumin and HES (MW 130,000) solutions
      on the physical properties of sodium hyaluronate (NaHA, MW 1.3 * 106) solution, a
      constituent of the ESL. Partial specific volumes (v) and intrinsic viscosities
      ([eta]) of NaHA in 0.15 M NaCl solution containing albumin or HES (1-3%) were
      calculated from densities and viscosities extrapolated at infinite dilutions.
      Flow activation energy (E) of 0.2% NaHA in phosphate-buffered saline containing
      albumin or HES was obtained from the temperature-dependence of viscosities. A 3%
      albumin solution decreased v of NaHA by 3% compared to HES. A 3% HES solution,
      but not albumin, decreased [eta] of NaHA by 34%, and decreased E values by 11%
      compared to albumin. These findings suggest that HES locally restricts NaHA
      dispersion, whereas albumin contracts NaHA structure.

PMID- 30241860
TI  - A polysaccharide from Eclipta prostrata alleviates experimental autoimmune
      encephalomyelitis through inhibiting Th17 cells.
AB  - Eclipta prostrata has long been used as a medicinal herb in China. EAP20-1, a
      homogeneous polysaccharide with anti-complementary activity had been obtained
      from E. prostrate by using anion-exchange and size-exclusion chromatography. In
      this study, we found that EAP20-1 could inhibit in vitro lymphocyte proliferation
      stimulated by concanavalin-A or anti-CD3/anti-CD28 antibodies. Furthermore, in
      experimental autoimmune encephalomyelitis (EAE) mice, EAP20-1 treatment relieved
      the clinical symptoms, accompanied by reduced neuroinflammation and demyelination
      in spinal cords. Mechanistically, EAP20-1 reduced the mRNA expression of
      interleukin (IL)-17, IL-22, and RAR-related orphan receptor gamma t (RORgammat)
      in the spleen; inhibited auto-reactive T cell proliferation and decreased the
      percentage of Th17 cells in response to myelin oligodendrocyte glycoprotein
      (MOG35-55) ex vivo. Moreover, EAP20-1 directly inhibited naive CD4 + T cells
      differentiate into Th17 cells in vitro. These results indicating EAP20-1 could
      benefit EAE through inhibiting Th17 cell differentiation and suggesting a
      therapeutic potential of EAP20-1 in MS.

PMID- 30241861
TI  - Synthesis of cationic alkylated chitosans and an investigation of their
      rheological properties and interaction with anionic surfactant.
AB  - Two methods were used to alkylate high MW chitosan with glycidyltrimethylammonium
      chloride (GTAC) in order to produce chitosan derivatives that are water-soluble
      throughout the pH range. In addition, a novel chitosan derivative was created by
      alkylating one of the products with the GTAC analogue Quab 342 containing C12
      alkyl chains. The phase behaviour and rheological characteristics of the chitosan
      derivatives were studied in the presence of anionic surfactant. The derivatives
      were found to form soluble complexes at low and high SDS concentrations and that
      the Quab 342 derivative was able to form gels.

PMID- 30241862
TI  - Polysaccharide from fermented Momordica charantia L. with Lactobacillus plantarum
      NCU116 ameliorates type 2 diabetes in rats.
AB  - The influence of Lactobacillus plantarum-fermentation on the structure and anti
      diabetic effects of Momordica charantia polysaccharides were evaluated. High-fat
      diet and streptozotocin-induced type 2 diabetic rats were administrated with
      polysaccharides from fermented and non-fermented Momordica charantia (FP and NFP)
      for 4 weeks. Fermentation affected the physicochemical characterization,
      monosaccharide composition, molecular weight, and viscosity of Momordica
      charantia polysaccharides. Treatment with FP significantly ameliorated
      hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress in diabetic
      rats compared with NFP. Moreover, the diversity and abundance of gut microbiota
      (Lactococcus laudensis and Prevotella loescheii) in diabetic rats were notably
      increased by treatment with FP in comparison to NFP. Meanwhile, FP-treated
      diabetic rats exhibited more colonic short-chain fatty acids (SCFAs) and lower pH
      values than that in NFP-treated rats. Overall, Lactobacillus plantarum
      fermentation could enhance the anti-diabetes effects of Momordica charantia
      polysaccharides in rats by modifying the structure of polysaccharides to optimize
      gut microbiota and heighten the production of SCFAs.

PMID- 30241863
TI  - Fucosylated chondroitin sulfate oligosaccharides from Isostichopus badionotus
      regulates lipid disorder in C57BL/6 mice fed a high-fat diet.
AB  - Fucosylated chondroitin sulfate (fCS) and its depolymerized derivative (DfCS),
      prepared from sea cucumbers, are well-known for their anticoagulant activity.
      However, their other functional activities are poorly understood. Recently, we
      obtained fCS oligosaccharides from Isostichopus Badionotus by a modified
      controllable Fenton-system, named as DfCS-Ib. The functional activities of these
      oligosaccharides are still unclear. The present study investigated anti
      hyperlipidemic activity of DfCS-Ib using a high-fat diet (HFD)-fed mice model.
      The results indicated that DfCS-Ib reduced obesity, hyperlipidemia, and
      inflammation caused by HFD. Meanwhile, DfCS-Ib increased the mRNA expression of
      PPARgamma and decreased the mRNA expression of leptin, aP2, and F4/80 in fat
      tissue. Transcriptome analysis indicated that DfCS-Ib normalized the expressions
      of genes regulating lipid metabolism. Our results suggested that DfCS-Ib can
      alleviated lipid disorder by reducing lipid synthesis and promoting lipid
      lipidolysis. DfCS-Ib can act as a functional agent to regulate lipid disorder.

PMID- 30241864
TI  - A pectin from fruits of Lycium barbarum L. decreases beta-amyloid peptide
      production through modulating APP processing.
AB  - Here, a pectin LBP1C-2 with the molecular weight of 99.8 kDa was purified from
      fruits of Lycium barbarum L. Its structure was elucidated as a backbone of
      alternate 1, 2-linked alpha-Rhap and 1, 4-linked alpha-GalpA, with branches of
      terminal (T) -, 1, 3-, 1, 6- and 1, 3, 6-linked beta-Galp, T-, 1, 5- and 1, 3, 5
      linked alpha-Araf and T-linked beta-Rhap substituted at C-4 of 1, 2, 4-linked
      alpha-Rhap. The cell-based experiments indicated that LBP1C-2 suppressed Abeta42
      production in a dose-dependent manner with no cytotoxicity. Further study showed
      that expression of beta-site APP cleaving enzyme 1 (BACE1) was attenuated by
      LBP1C-2, while expression of ADAM10 was up-regulated by LBP1C-2. Moreover, LBP1C
      2 promoted the expression of insulin-degradation enzyme (IDE). These results
      suggested that LBP1C-2 might be a leading compound for anti-Alzheimer's disease
      therapy by decreasing Abeta42 production through mediating BACE1 and ADAM10 as
      well as IDE expression.

PMID- 30241865
TI  - Antioxidative and hepatoprotective effects of enzymatic and acidic-hydrolysis of
      Pleurotus geesteranus mycelium polysaccharides on alcoholic liver diseases.
AB  - The present work investigated the antioxidant and hepatoprotective effects of
      acidic- and enzymatic-hydrolysis mycelium polysaccharide (AcMPS and EnMPS) from
      Pleurotus geesteranus on alcoholic liver disease (ALD) mice. The animal studies
      demonstrated that the polysaccharides had potential effects reflected by
      remitting alcoholic hepatitis, reducing lipid accumulation, preventing oxidative
      stress, improving inflammatory symptoms, and alleviating the liver functions by
      histopathologic observation. Results showed that AcMPS (yield of 84%) was
      composed of L-Rha, D-Rib, L-Ara, D-Glc, D-Man and D-Gal with the Mw of 3.49 * 104
      Da, while EnMPS (yield of 90%) was contained L-Rha, L-Ara, D-Gal and D-Glc with
      the Mw of 3.67 * 104 Da. Furthermore, the GC-MS analysis indicated that both
      AcMPS and EnMPS were beta-pyranoside polysaccharides with the (1->3)- and (1->6)
      linkages. The conclusions indicated that AcMPS and EnMPS could be used as natural
      drugs for preventing the ALD, and providing underlying hepatoprotective
      mechanisms, pharmaceutically.

PMID- 30241866
TI  - Cell interactions and cytotoxic studies of cellulose nanofibers from Curaua
      natural fibers.
AB  - Cellulose nanofibers (CNF) were isolated from Curaua fibers (Ananas erectifolius
      L. B. Smith) through a mechanical grinder preceded by mild chemical treatment.
      Morphology and surface characteristics of the fibers were followed until it
      reaches the nanoscale as long and flexible nanofibers. In aqueous suspensions,
      SAXS techniques revealed that such nanofibers present a twisted ribbon structure
      while rheological measurements demonstrate its high viscosity and a thixotropic
      behavior. These characteristics suggests the potential application of CNF in
      biomedical field, which, in turn, stimulates the toxicological studies of such
      materials. The obtained materials do not show any sign of cytotoxicity by direct
      or indirect assays for cell viability and cell morphology using Vero cells.
      Moreover, during the adhesion test, the cells demonstrated higher affinity to the
      CNF surface. It can be related to its surface properties and its obtaining
      conditions, which did not use any hazardous chemicals.

PMID- 30241867
TI  - Study of green nanocomposites based on corn starch and cellulose nanofibrils from
      Agave tequilana Weber.
AB  - Global environmental pollution issues caused by synthetic materials and the lack
      of practical utilization of the local industrial lignocellulosic waste, force
      Mexican researchers to produce new biobased sustainable materials that use
      industrial waste as a source of components. Herein, we show the preparation and
      characterization of environmentally friendly starch-based nanocomposites
      reinforced with cellulose nanofibrils (CNF) extracted from Agave tequilana Weber.
      Tensile, bending and impact mechanical properties of dried and hydrated
      nanocomposites were studied. Moreover, the water absorption capacity of the
      nanocomposites were measured and evaluated. The mechanical properties improved
      because of the presence of a small amount of CNF (1 wt%). This work demonstrates
      the importance of the addition of a natural biomodifier in a starch matrix to
      achieve better mechanical properties. Most importantly, this study highlights
      that lignocellulosic waste from the tequila industry can have a practical
      application, which is being a source of natural nanoreinforcements for
      preparation of all-biobased sustainable materials.

PMID- 30241869
TI  - Portal encasement: Significant CT findings to diagnose local recurrence after
      pancreaticoduodenectomy for pancreatic cancer.
AB  - BACKGROUND/OBJECTIVES: To demonstrate the utility of portal encasement as a
      criterion for early diagnosis of local recurrence (LR) after
      pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC).
      METHODS: A total of 61 patients who underwent PD for PDAC were included in this
      retrospective study. Portal stenosis was evaluated by sequential postoperative
      computed tomography (CT) scans and correlated with disease recurrence. In
      addition to the conventional LR diagnostic criterion of a growing soft tissue
      mass, LR was evaluated using portal encasement as an additional diagnostic
      criterion. Portal encasement was defined as progressive stenosis of the portal
      system accompanied by a soft tissue mass, notwithstanding the enlargement of the
      mass. RESULTS: Benign portal stenosis was found on the first postoperative CT
      imaging in 16 patients. However, stenosis resolved a median of 81 days later in
      all but one patient whose stenosis was due to portal reconstruction during PD.
      Portal encasement could be distinguished from benign portal stenosis based on the
      timing of emergence of the portal stenosis. Portal encasement developed in 13 of
      the 19 patients with LR, including 6 patients in whom the finding of portal
      encasement led to the diagnosis of LR a median of 147 days earlier with our
      diagnostic criterion compared with the conventional diagnostic criteria.
      CONCLUSIONS: Portal encasement should be considered as a promising diagnostic
      criterion for earlier diagnosis of LR after PD for PDAC.

PMID- 30241868
TI  - Thermal decomposition behaviors and kinetics of carrageenan-poly vinyl alcohol
      bio-composite film.
AB  - Pyrolysis characteristics of carrageenan-polyvinyl alcohol (CG-PVA) composite
      films were studied on a thermo gravimetric analyzer in N2 atmosphere. A stepwise
      procedure based on model-free Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose
      (KAS) and Friedman-Reich-Levi (FRL) methods were applied to calculate the
      apparent activation energies (E). The range of E for CG-PVA/LBP/K film was
      16.92~171.53 kJ/mol. Coats-Redfern and master-plots methods were utilized to
      investigate the most probable mechanisms for CG-PVA/LBP/K film. Further kinetic
      analysis was performed and revealed that five independent parallel reactions were
      supposed reasonably by deconvoluting DTG curves. Kinetic parameters of the
      corresponding five pseudo-components for CG-PVA/LBP/K film were separately
      calculated via Kissinger's method using the peak maximum temperature. It's
      concluded that lignin derivatives contributed the major part of degradation
      process. The orders of activation energy for pseudo components are E (PVA) >E
      (carrageenan) >E (biomass derivatives). The comprehensive analysis of pyrolysis
      kinetics may expand application fields of carrageenan based biocomposite films.

PMID- 30241870
TI  - Improved Detection of Pelvic Organ Prolapse: Comparative Utility of Defecography
      Phase Sequence to Nondefecography Valsalva Maneuvers in Dynamic Pelvic Floor
      Magnetic Resonance Imaging.
AB  - PURPOSE: To evaluate the utility of a defecography phase (DP) sequence in dynamic
      pelvic floor MRI (DPMRI), in comparison to DPMRI utilizing only non-defecography
      Valsalva maneuvers (VM). MATERIALS AND METHODS: Inclusion criteria identified 237
      female patients with symptoms and/or physical exam findings of pelvic floor
      prolapse. All DPMRI exams were obtained following insertion of ultrasound gel
      into the rectum and vagina. Steady-state free-precession sequences in sagittal
      plane were acquired in the resting state, followed by dynamic cine acquisitions
      during VM and DP. In all phases, two experienced radiologists performed blinded
      review using the H-line, M-line, Organ prolapse (HMO) system. The presence of a
      rectocele, enterocele and inferior descent of the anorectal junction, bladder
      base, and vaginal vault were recorded in all patients using the pubococcygeal
      line as a fixed landmark. RESULTS: DPMRI with DP detected significantly more
      number of patients than VM (p<0.0001) with vaginal prolapse (231/237, 97.5% vs.
      177/237, 74.7%), anorectal prolapse (227/237, 95.8% vs. 197/237, 83.1%),
      cystocele (197/237, 83.1% vs. 108/237, 45.6%), and rectocele (154/237, 65% vs.
      93/237, 39.2%). The median cycstocele (3.2cm vs. 1cm), vaginal prolapse (3cm vs.
      1.5cm), anorectal prolapse (5.4cm vs. 4.2cm), H-line (8cm vs. 7.2cm) and M-line
      (5.3cm vs. 3.9cm) were significantly higher with DP than VM (p<0.0001).
      CONCLUSIONS: Addition of DP to DPMRI demonstrates a greater degree of pelvic
      floor instability as compared to imaging performed during VM alone. Pelvic floor
      structures may show mild descent or appear normal during VM, with marked prolapse
      on subsequent DP images.

PMID- 30241871
TI  - Deprescribing: An educational imperative.
AB  - The Bruyere Evidence-Based Deprescribing Guideline Symposium included a forum on
      health professional education that brought together health professionals,
      researchers, professional organization representatives and public members. The
      goal was to facilitate partnerships among educators and to build knowledge,
      skills and support for behaviour change to integrate the use of evidence-based
      deprescribing guidelines into health care professional education. Participant
      discussions were analyzed under the thematic headings of teaching, learning, and
      assessment, impact of heuristics in learning, the importance of patient/public
      understanding and the role of leadership in enabling curricular change to include
      deprescribing. Deprescribing is considered to be on a continuum with prescribing,
      and it was recognized that related skills are not consistently taught or
      assessed, which may be interpreted by learners and health professionals as being
      less important than diagnostic or other skills. Strategies used currently to
      teach prescribing may also imply that it is a technical skill, not enabling
      learners to understand that prescribing and deprescribing involve complex tasks
      requiring patient consultation. Social barriers to deprescribing were also
      discussed and the importance of patient perspective in teaching
      prescribing/deprescribing was recognized. Based on the symposium discussions, the
      authors make several recommendations that include better teaching of optimal
      prescribing and deprescribing within an interprofessional context, that education
      be supported from the pre-licensure, post-graduate levels through to continuing
      professional development, and that assessment, demonstrating competence in
      prescribing and deprescribing, be embedded within programs.

PMID- 30241872
TI  - Medication adherence and barriers among low-income, uninsured patients with
      multiple chronic conditions.
AB  - BACKGROUND: Poor adherence to long-term therapies is a public health concern that
      affects all populations. Little is known about the context of adherence in
      chronic diseases for the uninsured population in the United States. OBJECTIVE: To
      evaluate medication adherence and barriers among low-income, uninsured adults
      recently initiating new therapy for a chronic disease. METHODS: A cross-sectional
      study in two Community Health Centers located in Chatham County, Georgia, was
      performed between September and December 2015. Patients, randomly selected for
      inclusion in the study, were eligible if they had been prescribed medication for
      2 or more chronic conditions and had recently started a new medication regimen.
      The Morisky-Green-Levine questionnaire was used to assess adherence. Potential
      barriers were analyzed using the Multidimensional Model proposed by the World
      Health Organization-social and economic, healthcare team and system-related,
      condition-related, therapy-related, and patient-related factors. Multivariate
      logistic regression models were used to analyze factors associated with non
      adherence. RESULTS: A total of 150 participants were interviewed at 6 months
      after treatment initiation. Non-adherence was reported by 52% of the
      participants. Higher adjusted odds of non-adherence were observed in participants
      who did not receive information about their medications (adjusted odds ratio
      [AOR] = 2.40, 95% confidence interval [CI] = 1.01-5.74), did not regularly visit
      a primary health-care provider (AOR = 2.74, 95% CI = 1.09-6.88), and had changes
      in their treatment (AOR = 3.75, 95% CI = 1.62-8.70). Alternatively, adjusted odds
      of non-adherence were lower for patients who reported using pillboxes (AOR =
      0.31, 95% CI = 0.10-0.95), having help from a caregiver (AOR = 0.15, 95% CI =
      0.04-0.60), and integrating medication dosing into daily routines (AOR = 0.18,
      95% CI = 0.06-0.59). CONCLUSIONS: Medication non-adherence was common among low
      income, uninsured patients initiating therapy for chronic conditions. Several
      modifiable barriers highlight opportunities to address medication non-adherence
      through multidisciplinary interventions.

PMID- 30241873
TI  - Implementation study of an intermediate medication review in Belgian community
      pharmacies.
AB  - BACKGROUND: The Association of Pharmacists in Belgium (APB) and local pharmacy
      associations launched a pilot project in collaboration with research teams from
      three Belgian universities to study the impact and implementation-related issues
      of a medication review (MR) service type 2a in Belgian community pharmacies.
      OBJECTIVE: The aim of this paper is to describe the implementation process of the
      MR service and to present the implementation evaluation of the pilot study
      (testing stage). METHODS: The pilot project was a prospective observational study
      using mixed methods. The implementation evaluation was based on the RE-AIM model
      and the framework for the implementation of services in pharmacy (FISpH).
      Collected implementation outcomes were classified into four dimensions: reach,
      adoption, implementation and intent of maintenance. RESULTS: During the testing
      stage, 80 pharmacies participated in the study, but 25 dropped out (31%), mainly
      because of a reported lack of time (adoption). The 55 remaining pharmacies
      included 457 patients. Recruiting patients into the service was challenging for
      pharmacists as 48.5% of patients refused the pharmacists' proposal (reach).
      Internal organizational factors were major barriers for pharmacists, followed by
      the lack of adoption by the pharmacy team. Large pharmacies in which pharmacy
      owner led the project were observed to be more proactive in implementing the MR
      service by integrating organizational strategies to assist the implementation
      process (implementation). Interviewed pharmacists perceived this new service as a
      professionally satisfying activity. Among participating pharmacists, 92.5% found
      this service feasible in practice, but believed it required adapted resources to
      reorganize the internal pharmacy workload, additional support, such as broad
      based media campaigns to increase physicians' and patients' awareness and
      attitudes towards the service, and modified software (maintenance). CONCLUSIONS:
      The medication review service was implemented in 68% of participating pilot
      Belgian community pharmacies but would require adapted resources and supports for
      larger scale implementation.

PMID- 30241874
TI  - Implementing deprescribing guidelines into frontline practice: Barriers and
      facilitators.
AB  - A Bruyere Evidence-Based Deprescribing Guideline Symposium was held in March
      2018; one component focused on implementing deprescribing guidelines into
      practice. An interactive discussion activity allowed the 107 participants to
      share experiences and ideas concerning the barriers and facilitators that arise
      when moving deprescribing guidelines into frontline practice. Participants
      identified 8 broad challenges and problem areas. These included challenges and
      barriers that arise in the daily practices of pharmacists and prescribers and in
      other health care settings, and those related to existing policies, processes,
      and financial structures. They also identified 10 factors that facilitated
      implementation efforts, including: educating patients, caregivers, health care
      providers (HCPs) and staff; improving collaboration across practice disciplines;
      expanding the evidence for deprescribing; and fostering organizational cultures
      of deprescribing. The results indicate that participants are committed to
      deprescribing and are moving forward with efforts to bring about change.
      Participants recognize that the implementation of deprescribing is best conceived
      of as a comprehensive systems change, and that patients and the public need to be
      involved in deprescribing processes and activities.

PMID- 30241875
TI  - Deprescribing guidelines: An international symposium on development,
      implementation, research and health professional education.
AB  - Deprescribing is a clinically important and feasible innovation that ensures
      medication efficacy, reduces harms, and mitigates polypharmacy. It involves
      reducing doses or stopping medications that are not useful, no longer needed, or
      which may be causing harm. It may also involve changing to a safer agent or using
      non-pharmacological approaches for care instead. Clinical guidelines combined
      with behaviour changes (of health care providers (HCPs), the public, and health
      care decision-makers) are needed to integrate deprescribing into routine
      practice. Using rigorous international standards, the Bruyere Research Institute
      Deprescribing Guidelines research team validated a ground-breaking deprescribing
      guideline methodology and developed or co-developed 5 evidence-based
      deprescribing guidelines. In March 2018, the team hosted an international
      symposium convening HCPs, researchers, public agencies, policymakers, and patient
      advocates in Ottawa, Ontario, Canada. This 3-day symposium aimed to facilitate
      knowledge exchange amongst guideline developers, users, and the public; initiate
      partnerships and collaborations for new deprescribing guideline recommendations
      and effectiveness research; and to continue work on HCP deprescribing education
      activities. An interprofessional planning committee developed an overall agenda,
      and small groups worked on session objectives and formats for different
      components: methods for rigorous deprescribing guideline development,
      implementation experiences, research/evaluation experiences and educational
      needs. Through a series of keynote speakers, panel discussions, and small working
      groups, the symposium provided a forum for participants to meet one another,
      learn about their different experiences with deprescribing guidelines, and
      develop collaborations for future initiatives. One hundred thirty participants,
      from 10 countries and representing over 100 institutions and organizations took
      part. Symposium proceedings are presented in this issue of RSAP for sharing with
      the wider community engaged in the care of patients with problematic
      polypharmacy.

PMID- 30241876
TI  - Deprescribing: Future directions for research.
AB  - A World Cafe workshop was held at the Bruyere Evidence-Based Deprescribing
      Guidelines Symposium in March 2018 with 30 participants (researchers, clinicians,
      policy makers, stakeholders). This workshop explored priorities for future work
      in the field of deprescribing and deprescribing guidelines through group
      discussion. The discussions were guided by the following questions: (1) What are
      deprescribing research priorities (to inform guideline development), (2) What
      outcome measures are important for developing deprescribing guidelines, and (3)
      How do we evaluate the implementation and effectiveness of deprescribing
      guidelines? Discussion from all 3 questions identified 6 main priority areas: (1)
      conducting high-quality and long-term clinical trials that measure patient
      important outcomes, (2) focusing on patient involvement and perspectives, (3)
      investigating the pharmacoeconomics of deprescribing interventions, (4)
      understanding deprescribing interventions in different populations, (5)
      generating evidence on clinical management during deprescribing (e.g. managing
      adverse drug withdrawal effects, subsequent re-prescribing), and (6) implementing
      interventions in clinical practice. These topics represent what a group of
      experienced researchers, clinicians, and stakeholders in the field collectively
      felt was important to consider for design and implementation of future
      deprescribing studies. The aim is for these findings to stimulate future
      discussions and be considered by granting agencies, policy makers, deprescribing
      research networks, and individual researchers planning future deprescribing
      studies.

PMID- 30241877
TI  - Deprescribing recommendations: An essential consideration for clinical guideline
      developers.
AB  - One area of focus of the Bruyere Evidence-Based Deprescribing Guidelines
      Symposium held in March 2018 was encouraging the routine inclusion of
      deprescribing recommendations in clinical guidelines. Clinical guidelines often
      do not accommodate frailty or patients with multiple comorbid conditions. This
      can give rise to complex medication regimens and risk of medication harm. Despite
      monitoring and stopping treatment being a key part of rational prescribing,
      deprescribing is often overlooked in general and in the context of guidelines.
      There are several challenges to increasing deprescribing recommendations in
      clinical guidelines. These include limited evidence on the effects of
      deprescribing, lack of awareness among guideline developers, potential conflicts
      of interest, and lack of incentives for deprescribing research. To date,
      medicines regulators, payers, governments, and journals have not encouraged the
      inclusion of deprescribing recommendations in guidelines. The Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) system could
      address some of these challenges through its focus on values and preferences,
      distinct rating of quality of evidence and strength of recommendations,
      downgrading quality due to indirect evidence, and an explicit approach to
      conflicts of interest. Further work to adapt GRADE methods to deprescribing could
      be of benefit. Establishing deprescribing recommendations as a routine part of
      clinical guidelines is an important opportunity to improve evidence-based
      clinical practice, and ultimately, patient care.

PMID- 30241878
TI  - Health care utilization and expenditures among adults with rheumatoid arthritis
      using specialty pharmaceuticals.
AB  - BACKGROUND: Despite the rising popularity of using specialty medications for
      patients with rheumatoid arthritis (RA), little is known about the use or
      spending on medical services among these patients. OBJECTIVE: The objective of
      this study was to investigate health care utilization and expenditures among
      patients with RA using specialty medications compared with those using non
      specialty (i.e., traditional) medications. METHODS: This was a retrospective
      cohort study using Medical Expenditure Panel Survey data from 2009 through 2015.
      Health care use and expenditures were examined using a (zero-truncated or zero
      inflated) negative binomial model and a generalized linear model with a log link
      function and gamma distribution (or a two-part model). RESULTS: Compared to
      patients with RA who were traditional medication users (TMUs), those categorized
      as specialty medication users (SMUs) were prescribed about 24% fewer medications
      (incidence rate ratio [IRR] = 0.76, 95% CI = 0.66-0.89) and received fewer office
      based visits (IRR = 0.84, 95% CI = 0.70-0.99). Although SMUs' spending on
      emergency department visits was lower, their spending on total health care was
      $14,570 higher than that of TMUs. Compared with TMUs, users of both specialty and
      traditional medications (BMUs) had fewer emergency department visits (IRR = 0.57,
      95% CI = 0.39-0.81) with less spending on emergency service use. Overall, BMUs'
      total health care spending was $5720 higher than TMUs' total spending.
      CONCLUSIONS: There were some differences in health care use and expenditures for
      treating RA between patients using specialty medications and those using
      traditional medications. Total health care spending was higher for SMUs/BMUs
      despite their less frequent use of some types of medical services and lower
      spending on emergency department visits, because of the high cost of specialty
      medications for RA. The high costs of specialty medications implies the
      importance of the efficient use of these medications.

PMID- 30241879
TI  - In-vitro antifungal susceptibility testing of lanoconazole and luliconazole
      against Aspergillus flavus as an important agent of invasive aspergillosis.
AB  - INTRODUCTION: The incidence of Aspergillus infections has recently increased
      remarkably in certain tropical and sub-tropical countries, with Aspergillus
      flavus being identified as the leading cause of infections after A. fumigatus.
      Lanoconazole (LAN) and luliconazole (LUL) are currently approved for topical
      treatment of cutaneous fungal infections. We aimed the in-vitro antifungal
      susceptibility testing of two imidazole, LAN and LUL against A. flavus. METHODS:
      One hundred and eighty-seven clinical and environmental A. flavus were tested
      originating from different climate zones of Iran between 2008 and 2015. The
      identification of all isolates was confirmed by using PCR-sequencing of beta
      tubuline ribosomal DNA gene. In-vitro antifungal susceptibility test was
      performed using CLSI guidelines against LAN, LUL, itraconazole (ITC),
      voriconazole (VRC), posaconazole (POS), Isavuconazole (ISA), amphotericin B
      (AMB), 5-flucytosine (5FC), caspofungin (CAS) and anidulafungin (AFG). The
      minimum inhibitory concentration (MIC) and minimum effect concentration (MEC)
      values were evaluated according to CLSI M38-A2 guidelines. RESULTS: The geometric
      mean MICs for tested antifungals, in increasing order, were: 0.009 MUg/mL for LUL
      (ranging from 0.004 to 0.062), 0.02 MUg/mL for LAN (ranging from 0.004 to 0.125),
      POS (0.10), ISA (0.16), ITC (0.24), VRC (0.27), AMB (1.8) and 5FC (63.06) MUg/mL.
      The mean value of MECs for AFG and CAS were 0.06 and 0.07, respectively.
      CONCLUSION: Overall, LUL and LAN showed the lowest MIC against all isolates of A.
      flavus. Further studies are required to evaluate the in-vivo efficacy of these
      agents, and the possibility of using these agents in systemic infections.

PMID- 30241880
TI  - High genetic stability in MDCK-SIAT1 passaged human influenza viruses.
AB  - MDCK-induced amino acid (AA) mutation, such as D151G/N in the neuraminidase (NA)
      of influenza A/H3N2 viruses, is of concern. MDCK-SIAT1 cells, modified
      derivatives with an increased expression of alpha2,6-linked sialic acid receptors
      are increasingly used due to their superiority in a viral recovery. However, MDCK
      SIAT1 induced AA mutations have not been fully examined. In this study, we
      compared NA and hemagglutinin (HA) genes of recent circulating influenza viruses
      isolated after an MDCK-SIAT1 passage with those directly obtained from the
      original samples. A total of 22 samples collected during the 2016-17 seasons
      included 9 A/H3N2, 5 H1N1pdm, and 8 B viruses. None of the deduced AA mutations
      in the NA or HA segments were detected after an MDCK-SIAT1 passage, except for
      one AA mutation in the NA of an influenza B virus sample. NA D151G/N changes were
      not seen in any of the MDCK-SIAT1 passaged A/H3N2 viruses, even in the small
      variants analysis conducted using deep sequencing. AA mutations induced by an
      MDCK-SIAT1 passage are currently rare, although careful observation is needed in
      the future.

PMID- 30241881
TI  - Liver transplantation in patients with ACLF and multiple organ failure: Time for
      priority after initial stabilization.

PMID- 30241882
TI  - Long-term effects of enzyme replacement therapy for Taiwanese patients with
      mucopolysaccharidosis IVA.

PMID- 30241883
TI  - Non-compaction cardiomyopathy and early respiratory failure in an adult
      symptomatic female carrier of centronuclear myopathy caused by a MTM1 mutation.
AB  - X-linked myotubular myopathy (XLMTM) is a rare neuromuscular condition caused by
      mutations in the MTM1 gene. Female carriers are believed to be usually
      asymptomatic; nevertheless, recent reports have displayed a wide a spectrum of
      clinical involvement in females suggesting that MTM1 mutations might be
      underestimated in this population. Here we report a 55-year-old woman manifesting
      with an abrupt respiratory decline, whose respiratory function tests revealed a
      severe restrictive ventilatory defect. The neurological examination identified
      mild proximal leg weakness and her cardiac evaluation showed a non-compaction
      cardiomyopathy with normal left ventricle function. Muscle biopsy was consistent
      with centronuclear myopathy. Next-generation sequencing of 49 genes related to
      congenital myopathies allowed the identification of a 4 bp deletion in the MTM1
      gene, leading to a truncating mutation previously described in males but for the
      first time reported in a female patient.

PMID- 30241884
TI  - Corrigendum to "Concentration of lead and mercury in collected vegetables and
      herbs from Markazi province, Iran: A non-carcinogenic risk assessment" [Food
      Chem. Toxicol. 113 (2018) 204-210].

PMID- 30241885
TI  - Sequence of refusals for donor quality, organ utilization, and survival after
      lung transplantation.
AB  - BACKGROUND: Lung donor utilization rates remain low, with many organs refused for
      donor quality. However, some centers have successfully transplanted these organs
      despite multiple refusals for donor quality (RDQs) by other centers. We
      hypothesized that the number of refusals due to donor quality does not impact
      post-transplant outcomes. METHODS: Lung transplants (LTxs) from 2006 to 2015,
      identified using the United Network for Organ Sharing (UNOS) database, were
      matched against the potential transplant recipient (PTR) data set by donor
      identification. Transplants were categorized into 2 groups: low RDQ (0 to 3 RDQs)
      and high RDQ (>3 RDQs). Post-transplant survival and predictors for high RDQ were
      observed using Kaplan-Meier and logistic regression analyses, respectively.
      RESULTS: Of 10,126 adult (>18 years) LTxs, 77% had at least 1 RDQ, with a median
      of 4 RDQs. Post-transplant 1-year survival was similar for both the low and high
      RDQ groups (p = 0.49). Furthermore, groups of recipients who received donors with
      an increasing number of RDQs (>3, >6, or >10) also had similar post-transplant 1
      year survival (p = 0.77). Treatment for rejection within 1 year and intubation at
      72 hours post-transplant were higher in the high RDQ group (p < 0.01). An inverse
      relationship was identified between the number of RDQs and likelihood of
      utilization. After 10 RDQs, the likelihood of utilization varied significantly by
      donor characteristics. CONCLUSIONS: Lung transplant survival is not associated
      with number of refusals due to donor quality. When determining whether an organ
      is suitable for transplant, the number of refusals due to donor quality should
      not influence one's decision, especially in this era of limited donor supply.

PMID- 30241887
TI  - Uric acid and cellular and humoral alloimmunity.

PMID- 30241886
TI  - Aortic root thrombosis in patients supported with continuous-flow left
      ventricular assist devices.
AB  - BACKGROUND: Aortic root thrombosis (ART) is a recently recognized complication of
      continuous-flow left ventricular assist device (CF-LVAD) therapy. However, little
      is known about the prevalence or clinical significance of this complication. The
      aim of our study was to systematically evaluate the incidence and significance of
      ART on CF-LVAD support. METHODS: We retrospectively reviewed all patients who
      underwent HeartMate II or HeartWare HVAD CF-LVAD implantation from April 2004
      through June 2016 at the Columbia University Medical Center. Echocardiography
      studies were systematically reviewed to identify patients who developed ART.
      Study outcomes included post-ART survival on CF-LVAD support, stroke, pump
      thrombosis, and clinically significant myocardial infarction (MI). RESULTS: The
      study cohort consisted of 436 CF-LVAD patients with 21 patients (4.8%) diagnosed
      with confirmed ART at a median time of 22 days (interquartile range [IQR] 3 to 56
      days) after CF-LVAD implantation. Involvement of the non-coronary cusp was the
      most common location of the ART (n = 15, 71.4%) and concomitant RV failure
      occurred in 14 patients (66.7%). Actuarial survival at 1 and 2 years after
      diagnosis of ART was 73.8% and 44.3%, respectively. ART was associated with a
      high rate of complications, including stroke (28.6%, 0.337 episode per patient
      year [EPPY]) and clinically significant MI (28.6%, 0.337 EPPY). CONCLUSIONS: ART
      is not uncommon after CF-LVAD implantation and is associated with significant
      morbidity and mortality in CF-LVAD patients. Given the early occurrence and high
      incidence of stroke and MI in patients who develop ART, surveillance and
      treatment strategies should be implemented to address this potentially
      devastating complication.

PMID- 30241888
TI  - C3d deposition and antibody-mediated rejection after lung transplantation.

PMID- 30241889
TI  - An international multicenter experience of biventricular support with HeartMate 3
      ventricular assist systems.
AB  - Significant right ventricular failure accompanying left ventricular failure was
      treated by implantation of the fully magnetically levitated centrifugal HeartMate
      3 ventricular assist device as biventricular (BiVAD) support in 14 patients at 6
      medical centers worldwide. The clinical details of this first multicenter
      experience are presented. Nine of these patients (64%) were alive as of January
      1, 2018. Eight of the 9 have continued on BiVAD support for 95 to 636 (mean 266)
      days: 7 at home, and 1 successfully transplanted after 98 days of support.

PMID- 30241890
TI  - Outcomes of patients with right ventricular failure requiring short-term
      hemodynamic support with the Impella RP device.
AB  - BACKGROUND: Right ventricular failure (RVF) after myocardial infarction,
      cardiotomy, or left ventricular assist device (LVAD) implantation increases
      morbidity and mortality. RVF also contributes to prolonged length of hospital
      stay and higher costs of care. The aim of this study was to evaluate the efficacy
      and safety of the Impella RP (Abiomed, Danvers, MA) in patients with severe RVF
      in these clinical settings. METHODS: This is a prospective cohort study of
      patients with severe RVF treated with a percutaneous right ventricular assist
      device (RVAD). Sixty patients with RVF refractory to medical treatment received
      the Impella RP device at 14 United States institutions as part of the Impella RP
      pre- and post-market approval studies. The study population included 2 cohorts:
      Cohort A, patients with RVF post-(LVAD) implantation (n = 31); and Cohort B,
      patients with RVF post-cardiotomy, heart transplant, or myocardial infarction (n
      = 29). The primary end-point was survival at 30 days or hospital discharge
      (whichever was longer). RESULTS: Mean age of patients was 59 +/- 15 years; 68%
      were males, 84% had a history of congestive heart failure, 44% had valvular
      disease, and 35% had pre-operative renal dysfunction. Patients received an
      average of 3.4 inotropes/vasopressors before the Impella RP implant. Patients
      were supported with the Impella RP for 4.0 +/- 1.5 (0.5 to 14) days. Hemodynamics
      improved immediately after initiation of device support, with an increase in
      cardiac index from 1.9 +/- 0.1 to 3.1 +/- 0.2 liters/min/m2 (p < 0.001) and a
      decrease in central venous pressure from 19.0 +/- 1 to 13 +/- 1 mm Hg (p <
      0.001). The overall survival at 30 days (or discharge) was 72%. CONCLUSIONS: To
      the best of our knowledge, this study represents the largest prospective study of
      patients with life-threatening RVF. Mechanical support with the Impella RP device
      in patients with RVF resulted in rapid hemodynamic improvement with reversal of
      shock and favorable survival.

PMID- 30241891
TI  - Urgent lung allocation system in the Scandiatransplant countries.
AB  - BACKGROUND: Throughout the world, the scarcity of donor organs makes optimal
      allocation systems necessary. In the Scandiatransplant countries, organs for lung
      transplantation are allocated nationally. To ensure shorter wait time for
      critically ill patients, the Scandiatransplant urgent lung allocation system
      (ScULAS) was introduced in 2009, giving supranational priority to patients
      considered urgent. There were no pre-defined criteria for listing a patient as
      urgent, but each center was granted only 3 urgent calls per year. This study aims
      to explore the characteristics and outcome of patients listed as urgent, assess
      changes associated with the implementation of ScULAS, and describe how the system
      was utilized by the member centers. METHODS: All patients listed for lung
      transplantation at the 5 Scandiatransplant centers 5 years before and after
      implementation of ScULAS were included. RESULTS: After implementation, 8.3% of
      all listed patients received urgent status, of whom 81% were transplanted within
      4 weeks. Patients listed as urgent were younger, more commonly had suppurative
      lung disease, and were more often on life support compared with patients without
      urgent status. For patients listed as urgent, post-transplant graft survival was
      inferior at 30 and 90 days. Although there were no pre-defined criteria for
      urgent listing, the system was not utilized at its maximum. CONCLUSIONS: ScULAS
      rapidly allocated organs to patients considered urgent. These patients were
      younger and more often had suppurative lung disease. Patients with urgent status
      had inferior short-term outcome, plausibly due to the higher proportion on life
      support before transplantation.

PMID- 30241892
TI  - Long-term postoperative control of eosinophilic chronic rhinosinusitis recurrence
      by inserting a steroid-eluting, sinus-bioabsorbable device reduces the dosage of
      oral steroid.
AB  - OBJECTIVE: We employed a steroid-eluting, sinus-bioabsorbable device for local
      treatment after surgery for eosinophilic chronic rhinosinusitis (ECRS). One year
      later, we investigated its efficacy in suppressing recurrence and reducing the
      use of oral steroids. METHODS: At one year after ECRS surgery, both 18 cases
      treated with a postoperative steroid-eluting, sinus-bioabsorbable device (Post-ST
      group) and 25 cases receiving conventional postoperative therapy (Post-Con group)
      showed significant improvement in the nasal symptoms (nasal obstruction, nasal
      discharge and olfactory dysfunction), CT score and threshold test (discrimination
      test). RESULTS: The olfactory dysfunction, CT score and threshold test were
      significantly improved in the Post-ST group compared with the Post-Con group, but
      the polyp score was not. The mean total number of oral steroid tablets ingested
      during one year after surgery was 24.3+/-2.8 tablets in the Post-ST group, which
      was significant lower than the 36.3+/-3.7 tablets used in the Post-Con group.
      CONCLUSION: The above results indicate that insertion of a steroid-eluting, sinus
      bioabsorbable device after ECRS surgery can reduce the oral steroid intake while
      maintaining long-term suppression of disease recurrence.

PMID- 30241894
TI  - The influence of intense ultrasound applied during pressing on the optical and
      cathodoluminescent properties of conventionally sintered YSZ ceramics.
AB  - The aim of the present work was to investigate the effect of the ultrasonic
      treatment on the optical and cathodoluminescent properties of translucent ZrO2-8
      mol.% Y2O3 (YSZ) ceramics obtained by conventional sintering of the pressed
      compacts. Treatment by intense ultrasound during dry pressing of the YSZ
      nanopowder leads to an increase in the relative density, a decrease in the pore
      size and an increase in the grain size of the sintered ceramics. It was shown
      that when the ultrasonic treatment is applied, the optical absorption cutoff
      wavelength of the sintered material is shifted to longer wavelengths, while the
      optical density of the material increases over the whole measurement spectrum.
      Samples subjected to ultrasonic treatment during pressing show higher intensity
      of luminescence than those obtained without the use of ultrasound, the shape of
      the luminescence spectra remaining unchanged. A correlation was obtained between
      the integral intensity of cathodoluminescence and the vacancy concentration in
      the sintered YSZ.

PMID- 30241893
TI  - Sonochemical degradation of antibiotics from representative classes
      Considerations on structural effects, initial transformation products,
      antimicrobial activity and matrix.
AB  - In this work, the sonochemical treatment (at 354 kHz and 88 W L-1) of six
      relevant antibiotics belonging to fluoroquinolones (ciprofloxacin and
      norfloxacin), penicillins (oxacillin and cloxacillin) and cephalosporins
      (cephalexin and cephadroxyl) classes was evaluated. Firstly, the ability of the
      process to eliminate them was tested, showing that sonodegradation of these
      antibiotics is strongly chemical structure-dependent. Thus, correlations among
      initial degradation rate of pollutants (Rd), solubility in water (Sw), water
      octanol partition coefficient (Log P) and topological polar surface area (TPSA)
      were tested. Rd exhibited a good correlation with Log P (i.e., the hydrophobicity
      degree of antibiotics). The considered penicillins had the fastest elimination
      and from the constitutional analysis using Lemke method was clear that the
      functional groups arrangement on these antibiotics made them highly hydrophobics.
      The penicillins were degraded closer at cavitation bubble than the
      fluoroquinolones or cephalosporins. The investigation of degradation products
      showed that sonogenerated hydroxyl radical primary attacked the beta-lactam ring
      of cloxacillin and cephalexin, whereas on norfloxacin induced a decarboxylation.
      On the other hand, the evolution of antimicrobial activity was also followed. It
      was evidenced the process capacity to remove antimicrobial activity from treated
      solutions, which was associated to the transformations of functional groups on
      antibiotics with important role for interaction with bacteria. Additionally,
      degradation of antibiotics having the highest (the most hydrophobic, i.e.,
      cloxacillin) and lowest (the most hydrophilic, i.e., cephadroxyl) Rd, was
      performed in synthetic matrices (hospital wastewater and seawater). Ultrasound
      degraded both antibiotics; for cloxacillin in such waters higher eliminations
      than in distilled water were observed (probably due to a salting-out effect
      exerted by matrix components). Meanwhile, for cephadroxyl a moderate inhibition
      of degradation in hospital wastewater and seawater respect to distilled water was
      found, this was related to competition by hydroxyl radical of the other
      substances in the matrices. These results show the quite selectivity of high
      frequency ultrasound to eliminate antibiotics form different classes even in
      complex matrices.

PMID- 30241895
TI  - Cytokines and beyond: Regulation of innate immune responses during helminth
      infection.
AB  - Parasitic helminth infection elicits a type 2 cytokine-mediated inflammatory
      response. During type 2 inflammation, damaged or stimulated epithelial cells
      exposed to helminths and their products produce alarmins and cytokines including
      IL-25, IL-33, and thymic stromal lymphopoietin. These factors promote innate
      immune cell activation that supports the polarization of CD4+ T helper type 2
      (Th2) cells. Activated innate and Th2 cells produce the cytokines IL-4, -5, -9,
      and -13 that perpetuate immune activation and act back on the epithelium to cause
      goblet cell hyperplasia and increased epithelial cell turnover. Together, these
      events facilitate worm expulsion and wound healing processes. While the role of
      Th2 cells in this context has been heavily studied, recent work has revealed that
      epithelial cell-derived cytokines are drivers of key innate immune responses that
      are critical for type 2 anti-helminth responses. Cutting-edge studies have begun
      to fully assess how other factors and pathways, including lipid mediators,
      chemokines, Fc receptor signaling, danger-associated molecular pattern molecules,
      and direct cell-cell interactions, also participate in shaping innate cell
      mediated type 2 inflammation. In this review, we discuss how these pathways
      intersect and synergize with pathways controlled by epithelial cell-derived
      cytokines to coordinate innate immune responses that drive helminth-induced type
      2 inflammation.

PMID- 30241897
TI  - September 2016 (vol. 215, no. 3; errors on page 316.e4).

PMID- 30241896
TI  - Role of hepatic stellate cell (HSC)-derived cytokines in hepatic inflammation and
      immunity.
AB  - In their quiescent state, Hepatic stellate cells (HSCs), are present in the sub
      endothelial space of Disse and have minimal interaction with immune cells.
      However, upon activation following injury, HSCs directly or indirectly interact
      with various immune cells that enter the space of Disse and thereby regulate
      diverse hepatic function and immune physiology. Other than the normal
      physiological functions of HSCs such as hepatic homeostasis, maturation and
      differentiation, they also participate in hepatic inflammation by releasing a
      battery of inflammatory cytokines and chemokines and interacting with other liver
      cells. Here, we have reviewed the role of HSC in the pathogenesis of liver
      inflammation and some infectious diseases in order to understand how the
      interplay between immune cells and HSCs regulates the overall outcome and disease
      pathology.

PMID- 30241898
TI  - Selective or universal screening for GBS in pregnancy (review).
AB  - Group B streptococcus (GBS) is the most common cause of early-onset neonatal
      sepsis in many countries and responsible for significant perinatal morbidity and
      mortality worldwide. Intrapartum antibiotic prophylaxis has been the mainstay of
      efforts to prevent early-onset GBS disease in recent decades, however it is
      unclear if women should be targeted based on the presence of clinical risk
      factors or by screening for GBS colonisation during pregnancy. Universal
      bacteriological screening of women in late pregnancy has been widely adopted but
      questions remain regarding its benefits and potential harms. Newer approaches to
      screening based on rapid point-of-care testing require further evaluation in
      randomised controlled trials to inform evidence-based practice. Given current
      preventive strategies do not protect against late onset disease and other
      sequelae of infection, maternal vaccination against GBS may present the best
      opportunity to reduce the global burden of invasive GBS disease in the future.

PMID- 30241899
TI  - WASP (Write a Scientific Paper): A review on the online medical resources
      available for medical training.
AB  - The global contemporary shift from paper-based to digital online resources has
      led to a revolutionary change in medical training. A multitude of online
      resources have been developed over the years that complement the medical
      professional's education, with greater access to knowledge, while enabling
      continuous medical education and development. These sources also allow us to keep
      up-to-date with medical news. The development of medical mobile applications
      (apps) has also facilitated medical training by providing versatility,
      flexibility and portability of updated medical resources.

PMID- 30241900
TI  - WASP (Write a Scientific Paper): The use of bibliographic management software.
AB  - In the scholarly environment, research findings are disseminated as journal
      papers which support/dispute extant knowledge or add further to what is already
      known. The entire manuscript needs to be cited (in-text) and referenced (at the
      end of article), in order for readers to ascertain the validity of the research
      claim/s. This must be done in proper and accepted fashion as plagiarism is a
      serious misdeed and inappropriate referencing mars a paper. Recent advancements
      in technology have led to the development of bibliographic management software
      tools. These tools are available as both commercial and open source software, and
      constitute a database wherein researchers search, store and cite references.
      Furthermore, authors can not only create personalized databases but also cite
      stored articles when compiling a manuscript or report or indeed any other form of
      document. This software obviates human manual inputting errors and inaccurate
      referencing, while conveniently enabling citation and referencing in any
      referencing style required, for example, after rejection, when an author must
      almost perforce resubmit a prepared but rejected paper to a different journal
      after suitable amendments.

PMID- 30241901
TI  - WASP (Write a Scientific Paper): Miscellaneous practical and material aspects.
AB  - To date, these WASP (Write a Scientific Paper) Best Practice Guidelines have
      dealt with various aspects of conducting research and writing it up. The papers
      in this set will review some practical and material aspects related to paper
      writing, particularly those pertaining to online resources that may potentially
      be utilized for research, how to structure a scientific paper using the
      conventional IMRaD (Introduction - Method - Results - and - Discussion) format,
      the use of bibliographic software for handling references, and the practicalities
      of dealing with a pathology lab for research purposes.

PMID- 30241902
TI  - Roles of aging in the production of light-flavored Daqu.
AB  - Daqu, a complex starting material used for Baijiu production, contains
      microorganisms, enzymes, and volatile compounds. An important part of Daqu
      production is aging, but the physicochemical and microbial changes during aging
      remain largely unknown. This study characterized "aging" according to
      physicochemical parameters, volatile compounds, and microbial communities. Aging
      was found to aid in the stabilization of the physicochemical parameters. Solid
      phase microextraction-gas chromatography-mass spectrometry was used to detect 72
      types of volatile compounds, which were predominantly alcohols, esters,
      aldehydes, alkenes, and alkanes. During aging, these compounds changed
      considerably, but their structures eventually stabilized. A high-throughput
      sequencing approach was used to analyze the changing composition of the microbial
      communities. In general, aging helped to enrich and stabilize the microbial
      population for making Baijiu. A total of 35 bacteria were detected as
      prokaryotic; among these, 15 had a diversity abundance ratio of more than 1%. The
      dominant bacteria were from the genus Pantoea, but these decreased with aging,
      while bacteria from Lactobacillus and Weissella increased. After aging for 2
      months, Pantoea, Lactobacillus and Weissella accounted for 0.4%, 54.0%, and
      18.9%, respectively. A total of 12 eukaryotic yeast and fungi were detected, the
      most abundant of which were Incertae_Sedis_incertae_sedis, Saccharomycopsis,
      Trichocomaceae_unclassified, Pichia, Tremellales_unclassified, and Galactomyces.
      During aging, the levels of Trichocomaceae_unclassified, Saccharomycopsis, and
      Galactomyces initially decreased but then increased. Pichia stayed unchanged as
      aging progressed. In conclusion, aging led to rebalanced interactions among Daqu
      microbes and was important in improving Daqu quality and ensuring its stability.

PMID- 30241903
TI  - Effects of ammonium and/or sulfide on methane production from acetate or
      propionate using biochemical methane potential tests.
AB  - The inhibitory effects of ammonium and sulfide on the methane production using
      acetate or propionate as a carbon source were investigated under different pH and
      temperature conditions. The methane production rate, duration of the lag phase,
      and inhibition threshold limit during methane production were estimated using the
      Gompertz equation and inhibitor mathematical model. The methane production rates
      at 53 degrees C were 2.3-2.7 times higher than those at 35 degrees C in the case
      of non-inhibitors. Increasing the NH4+ and/or S2- concentration decreased the
      methane production rate and increased the duration of the lag phase. For methane
      fermentation that was not acclimated to high NH4+ concentration, the critical
      NH4+ concentration beyond which methane fermentation would stop was 4000-5650
      mg/L, depending on the pH, temperature, and carbon source. When NH4+ and S2- were
      coexistent, the critical NH4+ concentration decreased to approximately 3800 mg/L
      when propionate was used and to approximately 4450 mg/L when acetate was used.
      However, no synergistic effect of NH4+ and S2- on the methane production rate was
      found at an NH4+ concentration of < 5000 mg/L and S2- concentration of 50 mg/L.

PMID- 30241904
TI  - Searching for high-binding peptides to bile acid for inhibition of intestinal
      cholesterol absorption using principal component analysis.
AB  - We previously proposed a new method for exploring functional peptides using both
      spot-synthesis peptide libraries and principal component analysis (PCA). Here, we
      applied these methods to determine if high-binding 6-mer peptides can be used on
      bile acid for the inhibition of intestinal cholesterol absorption. We used a
      binding assay of 512 basal 4-mer peptides to bile acid, and from these selected
      high-binding and low-binding peptides. PCA was performed on data from both these
      binding groups and many physicochemical variables of the 512 peptides tested, and
      then through this, the variables were reduced to two principal components (PCs).
      The peptides were plotted on the PCA chart, and we identified distinct clusters
      of high- and low-binding regions. These PCA regions were applied to 6-mer random
      peptides, and we identified 6-mer peptides with high and low binding capacity to
      bile acid. We confirmed that the average fluorescence intensity of high-binding
      peptides was 3.0-fold higher than that of low-binding peptides. We succeeded in
      identifying 6-mer peptides with high and low-binding affinity based on the PCA
      analysis of 4-mer peptides. These results were compared and discussed with regard
      to those acquired by our previous computational analysis based on neural
      networks.

PMID- 30241905
TI  - Comparison of white and blue light assessment of the upper and lower palpebral
      conjunctiva.
AB  - PURPOSE: To compare upper and lower eyelids in terms of palpebral redness, and
      roughness under two lighting conditions, and assess the extent of association
      between redness and roughness. METHODS: This was a cross-sectional study
      conducted at The Netherlands Contact Lens Congress (2016). The palpebral
      conjunctivae of the right, upper and lower eyelids of 250 subjects were assessed
      using a slit-lamp biomicroscope. White light was used to assess palpebral redness
      and roughness. Roughness was also assessed using cobalt blue light and
      fluorescein. A 5-point grading scale was used to grade the conditions. The
      average and maximum grades of 5 zones for the upper, and 3 zones for the lower
      eyelid were used in the non-parametric analysis. RESULTS: A significantly higher
      grading in palpebral roughness was found using fluorescein with blue light,
      compared to using white light, for both upper and lower eyelids (p < 0.001).
      Upper eyelids appeared significantly rougher than lower eyelids with white and
      blue light (p < 0.001). Correlations between redness and roughness for upper and
      lower eyelids were low to moderate (p = <0.001). CONCLUSION: Palpebral roughness
      was scored more highly with blue, than white light, therefore these methods
      should not be used interchangeably. Also, roughness was more apparent in the
      upper eyelid, therefore eyelids should be assessed separately. Palpebral redness
      and roughness should be considered independent variables due to the low to
      moderate correlation between them. It is therefore recommended to first assess
      both eyelids first for redness using white light, followed by examination with
      fluorescein and blue light to assess roughness.

PMID- 30241906
TI  - The role of the gap junction perinexus in cardiac conduction: Potential as a
      novel anti-arrhythmic drug target.
AB  - Cardiovascular disease remains the single largest cause of natural death in the
      United States, with a significant cause of mortality associated with cardiac
      arrhythmias. Presently, options for treating and preventing myocardial electrical
      dysfunction, including sudden cardiac death, are limited. Recent studies have
      indicated that conduction of electrical activation in the heart may have an
      ephaptic component, wherein intercellular coupling occurs via electrochemical
      signaling across narrow extracellular clefts between cardiomyocytes. The
      perinexus is a 100-200 nm-wide stretch of closely apposed membrane directly
      adjacent to connexin 43 gap junctions. Electron and super-resolution microscopy
      studies, as well as biochemical analyses, have provided evidence that perinexal
      nanodomains may be candidate structures for facilitating ephaptic coupling. This
      work has included characterization of the perinexus as a region of close inter
      membrane contact between cardiomyocytes (<30 nm) containing dense clusters of
      voltage-gated sodium channels. Here, we review what is known about perinexal
      structure and function and the potential that the perinexus may have novel and
      pivotal roles in disorders of cardiac conduction. Of particular interest is the
      prospect that cell adhesion mediated by the cardiac sodium channel beta subunit
      (Scn1b) may be a novel anti-arrhythmic target.

PMID- 30241907
TI  - Discovery of DS-6930, a potent selective PPARgamma modulator. Part I: Lead
      identification.
AB  - The lead identification of a novel potent selective PPARgamma agonist, DS-6930 is
      reported. To avoid PPARgamma-related adverse effects, a partial agonist was
      designed to prevent the direct interaction with helix 12 of PPARgamma-LBD.
      Because the TZD group is known to interact with helix 12, the TZD in efatutazone
      (CS-7017) was replaced to discover novel PPARgamma intermediate partial agonist
      8i. The optimization of 8i yielded 13ac with high potency in vitro. Compound 13ac
      exhibited robust plasma glucose lowering effects comparable to those of
      rosiglitazone (3 mg/kg) in Zucker diabetic fatty rats. Upon toxicological
      evaluation, compound 13ac (300 mg/kg) induced hemodilution to a lower extent than
      rosiglitazone; however, 13ac elevated liver enzyme activities. X-ray
      crystallography revealed no direct interaction of 13ac with helix 12, and the
      additional lipophilic interactions are also suggested to be related to the
      maximum transcriptional activity of 13ac.

PMID- 30241908
TI  - If you must operate on a patient presenting with purulent peritonitis secondary
      to sigmoid diverticular perforation...do not throw the baby out with the
      bathwater, not yet....

PMID- 30241909
TI  - Corrigendum to "Short communication: Apparent efficiency of colostral
      immunoglobulin G absorption in Holstein heifers" (J. Dairy Sci. 100:3282-3286).

PMID- 30241911
TI  - Letter to the editor regarding "The quantity of bone cement influences the
      anchorage of augmented pedicle screws in the osteoporotic spine: A biomechanical
      human cadaveric study" by Pishnamaz M et al. Clin Biomech 2018;52:14-19.

PMID- 30241912
TI  - Response to letter of Abraham et al.

PMID- 30241913
TI  - Manual lymph drainage may not have a preventive effect on the development of
      breast cancer-related lymphoedema in the long term: a randomised trial.
AB  - QUESTION: What are the short-term and long-term preventive effects of manual
      lymph drainage (MLD), when used in addition to information and exercise therapy,
      on the development of lymphoedema after axillary dissection for breast cancer?
      DESIGN: Randomised controlled trial with concealed allocation, blinded assessors
      and intention-to-treat analysis. PARTICIPANTS: Adults undergoing unilateral
      dissection for breast cancer were recruited, with 79 allocated to the
      experimental group and 81 to the control group. INTERVENTION: The experimental
      group received guidelines about prevention of lymphoedema, exercise therapy and
      MLD. The control group received the same guidelines and exercise therapy, but no
      MLD. The interventions in both groups were delivered for 6 months. OUTCOME
      MEASURES: The primary outcome was cumulative incidence of arm lymphoedema defined
      in four ways (>=200ml,>=2cm,>=5%, and>=10% increase), which represent the
      difference in arm volume or circumference between the affected and healthy sides
      compared with the difference before surgery. Secondary outcomes included point
      prevalence of lymphoedema, change in arm volume difference, shoulder range of
      movement, quality of life and function. RESULTS: Incidence rates were comparable
      between experimental and control groups at all follow-up measurements. Sixty
      months after surgery, the cumulative incidence rate for the>=200ml definition was
      35% for the experimental group versus 29% for the control group (RR 0.89, 95% CI
      0.51 to 1.54, p=0.45); for the>=2cm definition 35% versus 38% (RR 0.93, 95% CI
      0.59 to 1.45, p=0.73); for the>=5% definition 68% versus 53% (RR 1.28, 95% CI
      0.97 to 1.69, p=0.08) and for the>=10% definition 28% versus 24% (RR 1.18, 95% CI
      0.66 to 2.10, p=0.57). The secondary outcomes were comparable between the groups
      at most assessment points. CONCLUSION: Manual lymph drainage may not have a
      preventive effect on the development of breast cancer-related lymphoedema in the
      short and long term. TRIAL REGISTRATION: Netherlands Trial Register NTR 1055.
      [Devoogdt N, Geraerts I, Van Kampen M, De Vrieze T, Vos L, Neven P, Vergote I,
      Christiaens M-R, Thomis S, De Groef A (2018) Manual lymph drainage may not have a
      preventive effect on the development of breast cancer-related lymphoedema in the
      long term: a randomised trial. Journal of Physiotherapy 64: 245-254].

PMID- 30241914
TI  - Virtual Special Issue on low back pain.

PMID- 30241915
TI  - Finite-time consensus of Markov jumping multi-agent systems with time-varying
      actuator faults and input saturation.
AB  - This paper gives attention to the issue of finite-time leader-following consensus
      of nonlinear discrete-time multi-agent systems with Markov jump parameters. A
      robust fault-tolerant control protocol that takes the effect of time-varying
      actuator faults and actuator saturation into account is considered for the
      addressed system. The main purpose of the paper is to design a fault-tolerant
      controller such that the leader-following consensus of the addressed system is
      achieved over a prescribed finite-time interval. By using the Lyapunov functional
      approach, Abel's lemma and some properties of Kronecker product, a sufficient
      condition for the existence of fault-tolerant state feedback controller for the
      addressed system is presented and an explicit parameterization of such a
      controller is obtained. Eventually, a numerical example along with its simulation
      results is exploited to reflect the applicability of the proposed design method,
      wherein the robust performance of controller is exhibited despite the presence of
      actuator saturation and time-varying actuator faults.

PMID- 30241916
TI  - Commentary on the Forth International Congress on "Alcoholism and Stress: A
      Framework for Future Treatment Strategies".

PMID- 30241910
TI  - Connectivity Fingerprints: From Areal Descriptions to Abstract Spaces.
AB  - Fifteen years ago, Passingham and colleagues proposed that brain areas can be
      described in terms of their unique pattern of input and output connections with
      the rest of the brain, and that these connections are a crucial determinant of
      their function. We explore how the advent of neuroimaging of connectivity has
      allowed us to test and extend this proposal. We show that describing the brain in
      terms of an abstract connectivity space, as opposed to physical locations of
      areas, provides a natural and powerful framework for thinking about brain
      function and its variation across the brains of individuals, populations, and
      species.

PMID- 30241917
TI  - Value of DNA methylation in predicting curve progression in patients with
      adolescent idiopathic scoliosis.
AB  - BACKGROUND: There is considerable discordance in the curve progression of
      adolescent idiopathic scoliosis (AIS) patients between monozygotic (MZ) twins,
      indicating that nongenetic factors must be involved in the curve progression of
      AIS patients. Epigenetic processes may constitute one of these factors and have
      not yet been investigated in relation to curve progression in AIS patients.
      METHODS: The genome and methylome of peripheral monocytes were compared between
      MZ twins discordant for curve progression. Sets of differentially methylated
      sites were validated using the MassARRAY platform of Sequenome on additional
      samples. RESULTS: In the discovery study, we found evidence suggesting a lack of
      differences at the genome sequence level and the presence of epigenetic
      differences related to the curve progression of AIS patients. The top 4
      differentially methylated CpG sites associated with curve severity were tested,
      and only site cg01374129 (CpG site located at chr8:122583383, Hg19) was confirmed
      in two replication cohorts. The methylation levels of site cg01374129 were
      significantly lower in the progression group than in the nonprogression group.
      Cox regression analysis demonstrated that hypo-methylation of site cg01374129 was
      an independent prognostic factor for curve severity. Site cg01374129 methylation
      as a marker achieved a sensitivity of 76.4% and a specificity of 85.6% in
      differentiating between samples from patients with and without curve progression
      (AUC = 0.827; 95% CI: 0.780 to 0.876). CONCLUSION: Increased curvature is
      associated with decreased methylation at site cg01374129. Our results indicate
      that methylation of site cg01374129 may therefore serve as a promising biomarker
      in differing between patients with and without curve progression.

PMID- 30241920
TI  - There are probably no important differences in postoperative pain levels between
      positive and negative pressure irrigation during root canal treatment of
      mandibular molars.

PMID- 30241921
TI  - There is probably high variability in the incidence of root resorption after
      replantation of avulsed teeth across and within types of teeth and resorption.

PMID- 30241918
TI  - Disrupted asymmetry of inter- and intra-hemispheric functional connectivity in
      patients with drug-naive, first-episode schizophrenia and their unaffected
      siblings.
AB  - BACKGROUND: Lack of normal asymmetry in the brain has been reported in patients
      with schizophrenia. However, it remains unclear whether disrupted asymmetry
      originates from inter-hemispheric functional connectivity (FC) and/or intra
      hemispheric FC in this patient population. METHODS: Forty-four patients with drug
      naive, first-episode schizophrenia, 42 unaffected siblings, and 44 healthy
      controls underwent resting-state functional magnetic resonance imaging (fMRI)
      scan. The parameter of asymmetry (PAS) and support vector machine (SVM) were used
      to analyze the data. Patients were treated with olanzapine for 8 weeks. FINDINGS:
      Compared with healthy controls, patients showed lower PAS scores in the left
      middle temporal gyrus (MTG)/inferior temporal gyrus (ITG), left posterior
      cingulate cortex (PCC)/precuneus and left angular gyrus, and higher PAS scores in
      the left precentral gyrus/postcentral gyrus. Unaffected siblings also showed
      lower PAS scores in the left MTG/ITG and left PCC/precuneus relative to healthy
      controls. Further, SVM analysis showed that a combination of the PAS scores in
      these two clusters in patients at baseline was able to predict clinical response
      after 8 weeks of olanzapine treatment with 77.27% sensitivity, 72.73%
      specificity, and 75.00% accuracy. INTERPRETATION: The present study suggests
      disrupted asymmetry of inter- and intra-hemispheric FC in drug-naive, first
      episode schizophrenia; in addition, a reduced asymmetry of inter-hemispheric FC
      in the left MTG/ITG and left PCC/precuneus may serve as an endophenotype for
      schizophrenia, and may have clinical utility to predict response to olanzapine
      treatment. FUND: The National Key R&D Program of China and the National Natural
      Science Foundation of China.

PMID- 30241919
TI  - PI3Kgamma promotes vascular smooth muscle cell phenotypic modulation and
      transplant arteriosclerosis via a SOX9-dependent mechanism.
AB  - BACKGROUND: Transplant arteriosclerosis (TA) remains the major cause of chronic
      graft failure in solid organ transplantation. The phenotypic modulation of
      vascular smooth muscle cells (VSMCs) is a key event for the initiation and
      progression of neointimal formation and TA. This study aims to explore the role
      and underlying mechanism of phosphoinositide 3-kinases gamma (PI3Kgamma) in VSMC
      phenotypic modulation and TA. METHODS: The rat model of aortic transplantation
      was established to detect PI3Kgamma expression and its role in neointimal
      formation and vascular remodeling in vivo. PI3Kgamma shRNA transfection was
      employed to knockdown PI3Kgamma gene. Aortic VSMCs was cultured and treated with
      TNF-alpha to explore the role and molecular mechanism of PI3Kgamma in VSMC
      phenotypic modulation. FINDINGS: Activated PI3Kgamma/p-Akt signaling was observed
      in aortic allografts and in TNF-alpha-treated VSMCs. Lentivirus-mediated shRNA
      transfection effectively inhibited PI3Kgamma expression in medial VSMCs while
      restoring the expression of VSMC contractile genes, associated with impaired
      neointimal formation in aortic allografts. In cultured VSMCs, PI3Kgamma blockade
      with pharmacological inhibitor or genetic knockdown markedly abrogated TNF-alpha
      induced downregulation of VSMC contractile genes and increase in cellular
      proliferation and migration. Moreover, SOX9 located in nucleus competitively
      inhibited the interaction of Myocardin and SRF, while PI3Kgamma inhibition
      robustly reduced SOX9 expression and its nuclear translocation and repaired the
      Myocardin/SRF association. INTERPRETATION: These results suggest that PI3Kgamma
      plays a critical role in VSMC phenotypic modulation via a SOX9-dependent
      mechanism. Therefore, PI3Kgamma in VSMCs may represent a promising therapeutic
      target for the treatment of TA. FUND: National Natural Science Foundation of
      China.

PMID- 30241922
TI  - Readibility, Understandability, and Quality of Online Education Materials for
      Vocal Fold Nodules.
AB  - OBJECTIVE: Vocal fold nodules are benign vocal fold lesions that can adversely
      affect quality of life. Differential diagnosis and treatment modalities of this
      disease are variable and patients often tend to use online materials to learn the
      insights. Access to knowledge via Internet is very easy; however, it is important
      to choose wisely because false and biased information might lead the patient to
      an inappropriate decision. In this study, we have evaluated the quality,
      readability, and understandability of online materials for vocal fold nodules.
      METHODS: An Internet search was performed for "Vocal fold nodule," "vocal fold
      nodule treatment," and "voice therapy for vocal fold nodule" by using Google
      search engine. Readability of each website was evaluated by using
      www.readable.io. Understandability and actionability of pages were measured by
      using the Patient Education Materials Assessment Tool (PEMAT). In the end,
      DISCERN instrument was used to measure the quality of information presented.
      RESULTS: After exclusion, total of 26 web pages were evaluated during the study.
      Four web pages graded as A level, 5 as B level, 11 as C level, and 5 as D level
      for language use. Average grade level for all of the web pages is 11.14 +/- 1.75.
      Overall understandability score was found 59.0+ 12.1 (26.7-77.1), and overall
      quality score was measured 34.95 + 6.58 (53.75-26.5). CONCLUSION: The quality,
      readability, and understandability of the written materials are very low and in
      order for patients to read and learn from the online sources, contents of the
      written materials should be revised.

PMID- 30241923
TI  - Molecularly Imprinted Polymers in Electrochemical and Optical Sensors.
AB  - Molecular imprinting is the process of template-induced formation of specific
      recognition sites in a polymer. Synthetic receptors prepared using molecular
      imprinting possess a unique combination of properties such as robustness, high
      affinity, specificity, and low-cost production, which makes them attractive
      alternatives to natural receptors. Improvements in polymer science and
      nanotechnology have contributed to enhanced performance of molecularly imprinted
      polymer (MIP) sensors. Encouragingly, recent years have seen an increase in high
      quality publications describing MIP sensors for the determination of
      biomolecules, drugs of abuse, and explosives, driving toward applications of this
      technology in medical and forensic diagnostics. This review aims to provide a
      focused overview of the latest achievements made in MIP-based sensor technology,
      with emphasis on research toward real-life applications.

PMID- 30241924
TI  - The Current Scientific and Regulatory Landscape in Advancing Integrated
      Continuous Biopharmaceutical Manufacturing.
AB  - There is a trend across the pharmaceutical sector toward process intensification
      and continuous manufacturing to produce small-molecule drugs or biotechnology
      products. For biotechnology products, advancing the manufacturing technology
      behind upstream and downstream processes has the potential to reduce product
      shortages and variability, allow for production flexibility, simplify scale-up
      procedures, improve product quality, reduce facility footprints, increase
      productivity, and reduce production costs. On the upstream side of biotechnology
      manufacturing, continuous perfusion cell cultures are fairly well established.
      However, truly integrated continuous biomanufacturing requires the uninterrupted
      connection of continuous unit operations (upstream and downstream) with no
      isolated intermediate or hold steps occurring between them. This work examines
      the current scientific and regulatory landscape surrounding the implementation of
      integrated continuous biomanufacturing.

PMID- 30241925
TI  - Using Smartphones to Collect Quantitative Data on Lower Limb Functionality in
      People Who Have Suffered a Stroke.
AB  - GOAL: The main objective was to use the inertial sensor integrated into a
      smartphone to collect quantitative data on lower limb functioning during
      execution of the timed up and go test and sit to stand test by people in the
      acute stage of stroke. The secondary objective was to analyze whether smartphones
      provide reliable quantitative data on performance of these functional tests.
      MATERIAL AND METHODS: Cross-sectional analytical study involving 8 elderly people
      (M age = 67.50 years). Both tests were performed to parametrize and analyze the
      functionality, balance, and strength of lower limbs using an inbuilt inertial
      sensor of the smartphone. Time, difference in trunk position, angular
      displacement, angular velocity, and angular acceleration were measured and
      calculated for each stage at which both functional tests were divided. RESULTS:
      The obtained results highlight the similarity in the angular displacement during
      the 2 stages into which the sitting-standing (flexion: 38.85 degrees  and
      extension: 38.10 degrees ) and the standing-sitting (flexion: 36.42 degrees  and
      extension: 36.45 degrees ) phases were divided. Mean velocities of .59 m/s and
      .61 m/s were registered during outward and return walking phases. The intra- and
      interobserver reliability of variables recorded with the inbuilt inertial sensor
      ranged from .860 to .897. CONCLUSIONS: Balance and muscle strength problems of
      stroke patients gave rise to the use of compensatory mechanisms when getting up
      from or sitting down in a chair and resulted in a reduction in walking speed that
      is sufficient to make walking in community contexts difficult. Smartphones has
      excellent reliability when used to quantify lower limb functioning in stroke
      patients.

PMID- 30241926
TI  - Differential Clinical Implications of Current Recommendations for the Evaluation
      of Left Ventricular Diastolic Function by Echocardiography.
AB  - BACKGROUND: Classification of left ventricular diastolic function (LVDF) by
      echocardiography is controversial. The aim of this study was to evaluate the
      impact of the last 2016 recommendations for LVDF evaluation on brain natriuretic
      peptide (BNP) levels, proportion of final heart failure (HF) diagnosis, and
      cardiovascular outcomes. METHODS: Outpatients with first consultation at a one
      stop HF clinic (2009-2014) were screened. The initial visit included
      echocardiography with LVDF evaluation and determination of BNP level. HF
      diagnosis was confirmed or ruled out at the end of the visit. Cardiovascular
      events during follow-up were recorded. LVDF classification was originally
      performed with the 2009 recommendations and reevaluated using the 2016
      recommendations. RESULTS: A total of 157 patients (mean age 73.24 +/- 10.3 years;
      70.1% women) were included. Originally (2009 recommendations), most of the
      patients were classified with grade I diastolic dysfunction (DD; 67.5%). After
      the reanalysis using the 2016 recommendations, 49% were reclassified with normal
      LVDF. These subjects showed lower BNP levels (40.8 pg/mL) and a lower proportion
      of HF diagnosis (9.6%). Another part of the initial grade I DD group (31.1%) was
      reclassified with indeterminate LVDF; they had intermediate BNP levels,
      proportion of HF, and rate of cardiovascular events. Lower reclassification rates
      were observed in the other groups of DD. Kaplan-Meier survival curves showed
      significantly better prognostic stratification after the reclassification (P =
      .539 vs P = .003). CONCLUSIONS: Current recommendations for the evaluation of
      LVDF by echocardiography resulted in more accurate classification of patients,
      according to their BNP levels, HF diagnosis, and cardiovascular outcomes,
      especially for those patients previously classified with grade I DD.

PMID- 30241927
TI  - The Development of Color Doppler Echocardiography: Innovation and Collaboration.
AB  - Conception, development, innovation, introduction, and validation are some of the
      steps in the introduction of new technologies and their clinical applications.
      More than 50 years ago, Doppler techniques and applications were introduced into
      echocardiography. An important further addition was the introduction of color as
      a medium for the display of Doppler information. The amplitude of the returning
      ultrasound signal has been used to generate a black and white image of structure.
      The phase shift between the transmitted and returning Doppler signal has been
      used to display Doppler shift information in color. This review focuses on some
      of the resources critical to this new development, the challenges imposed by the
      introduction of a new color display, and some of the early clinical validation
      and applications of color Doppler echocardiography.

PMID- 30241928
TI  - Celebrating (More Than) 50 Years of Doppler Echocardiography.

PMID- 30241929
TI  - Feasibility of New Transthoracic Three-Dimensional Echocardiographic Automated
      Software for Left Heart Chamber Quantification in Children.
AB  - BACKGROUND: New three-dimensional echocardiographic automated software
      (HeartModel) is now available to quantify the left heart chambers. The aims of
      this study were to assess the feasibility, reproducibility, and analysis time of
      this technique and its correlation with manual three-dimensional echocardiography
      (3DE) and cardiac magnetic resonance (CMR) in children. METHODS: Ninety-two
      children (5-17 years of age) were prospectively included in two separate
      protocols. In protocol 1, 73 healthy children underwent two-dimensional and three
      dimensional transthoracic echocardiography. Left ventricular (LV) end-diastolic
      volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), and
      left atrial volume at ventricular end-systole (LAV) by automated 3DE were
      compared with the same measurements obtained using manual 3DE. In protocol 2,
      automated three-dimensional echocardiographic measurements from 19 children with
      cardiomyopathy were compared with CMR values. RESULTS: Automated 3DE was feasible
      in 77% of data sets and significantly reduced the analysis time compared with
      manual 3DE. In protocol 1, there were excellent correlations for LVEDV, LVESV,
      and LAV between automated 3DE and manual 3DE (r = 0.89 to 0.99, P < .0001 for
      all) and a weak correlation for LVEF, despite contour adjustment (r = 0.57, P <
      .0001). Automated 3DE overestimated LVEDV, LVEF, and LAV with small biases and
      underestimated LVESV with wider bias. With contour adjustment, the biases and
      limits of agreement were reduced (bias: LVEDV, 0.9 mL; LVESV, -1.2 mL; LVEF,
      2.2%). In protocol 2, correlations between automated 3DE with contour edit and
      CMR were good for LV volumes and LAV (r = 0.76 to 0.94, P < .0003 for all) but
      remained weak for LVEF (r = 0.46, P = .05). Automated 3DE slightly underestimated
      LV volumes (relative bias, -7.2% to -7.8%) and significantly underestimated LAV
      (relative bias, -31.6%). The limits of agreement were clinically acceptable only
      for LVEDV. Finally, test-retest, intraobserver, and interobserver variability
      values were low (<12%). CONCLUSIONS: HeartModel is feasible, reproducible, faster
      than manual 3DE, and comparable with manual 3DE for measurements of LV and left
      atrial volumes in children >5 years of age. However, compared with CMR, only
      LVEDV measured by automated 3DE with contour edit seems applicable for clinical
      practice.

PMID- 30241930
TI  - Efficacy of Ultralow-Dose Valganciclovir Chemoprophylaxis for Cytomegalovirus
      Infection in ABO-Incompatible Kidney Transplantation Recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection can increase morbidity and mortality
      in kidney transplant (KT) patients. Chemoprophylaxis with valganciclovir (VGCV)
      is recommended for ABO-incompatible (ABOi) KT patients as it significantly
      reduces CMV disease and infection. The recommended dose of VGCV for prevention of
      CMV in a KT recipient is 900 mg once daily, and the treatment duration is 6
      months. However, because it is expensive, sufficient amounts might not be
      administered. METHODS: We investigated whether ultralow-dose VGCV (450 mg every
      other day) and short dosing period (3 months) was sufficient to prevent CMV
      infection after ABOi KT. We retrospectively evaluated 74 adult CMV-seropositive
      donor/CMV-seropositive recipient (D+/R+) ABOi KT recipients from June 2009 to
      July 2016 who received ultralow-dose VGCV prophylaxis for 3 months. The primary
      outcome was occurrence of CMV infection. Secondary outcomes were leukopenia and
      thrombocytopenia. RESULT: All patients received intravenous rituximab 200 mg once
      and plasmapheresis for reduction of anti-A/B antibodies and interleukin-2
      antibodies before undergoing ABOi KT. Mean prophylaxis and follow-up durations
      were 3 and 52 months, respectively. One patient died of bacterial pneumonia. Four
      patients lost graft function and were undergoing hemodialysis; 3 cases were
      caused by antibody-mediated rejection, and 1 was due to mechanical complication
      after surgery. Fortunately, CMV infection did not occur in any patient.
      CONCLUSION: Ultralow-dose VGCV is an effective prophylaxis for D+/R+ ABOi KT
      recipients. Especially, ultralow-dose VGCV CMV infection prevention protocol in
      Asian populations reduced the side effects and cost.

PMID- 30241931
TI  - Climbing-Related Injury Among Adults in the United States: 5-Year Analysis of the
      National Emergency Department Sample.
AB  - INTRODUCTION: Rock climbing and mountaineering are popular outdoor recreational
      activities. More recently, indoor climbing has become popular, which has
      increased the number of persons at risk for climbing-related injuries. The
      purpose of this study was to assess the morbidity, mortality, and healthcare cost
      due to climbing-related injury among persons presenting to US emergency
      departments (ED). METHODS: We performed a retrospective analysis of the 2010 to
      2014 National Emergency Department Sample database, a nationally representative
      sample of all visits to US EDs. Rock climbing, mountain climbing, and wall
      climbing injuries were identified using International Classification of Diseases,
      Ninth Revision, Clinical Modification codes (E004.0). Outcomes evaluated included
      morbidity, mortality, inpatient admission, and costs. Adjusted analyses
      accounting for survey methodology were performed. RESULTS: A weighted-estimate
      15,116 adult ED visits were associated with climbing-related injury. Patient age
      was 32.8+/-14.7 (mean+/-SD) (95% CI: 32.1-33.5) y, and 62% of patients were male.
      The majority of the injuries occurred in the Western census region (9593; 63%).
      Less than 1% of all climbing-related visits resulted in death. Only of injury
      severity score >15 was associated with death (P = 0.005). A total of 1610 (11%)
      of patients were admitted as inpatients. Accounting for ED and inpatient costs,
      climbing-related injuries cost the US healthcare system approximately $102 (95%
      CI: $75-130) million USD for the 5-y period, averaging $20+/-9.5 million USD per
      y. CONCLUSIONS: Most persons with climbing-related injuries presenting to EDs do
      not require inpatient admission. Although death is rare among patients with
      climbing-related injuries, the costs of injuries in survivors remain high.

PMID- 30241932
TI  - Association between storage age of transfused red blood cells and clinical
      outcomes in critically ill adults: A meta-analysis of randomized controlled
      trials.
AB  - OBJECTIVES: A meta-analysis was performed to assesses the effect of storage age
      of transfused red blood cells (RBCs) upon clinical outcomes in critically ill
      adults. METHODS: A comprehensive search was conducted in the PubMed, OVID, Web of
      Science and Cochrane databases for randomized controlled trials (RCTs) comparing
      the transfusion of fresher versus older RBCs in critically ill adults from
      database inception to December 2017. The primary endpoint was short-term
      mortality, and the secondary endpoints were the duration of intensive care unit
      (ICU) and hospital stay. The pooled odds ratios (OR) and mean differences (MD)
      were calculated using Stata/SE 11.0. RESULTS: A total of six RCTs were
      identified, of which four were multicenter studies, while two were single-center
      trials. The pooled results indicated that the transfusion of fresher RBCs was not
      associated to a decrease in short-term mortality compared with the transfusion of
      older RBCs (random-effects OR=1.04, 95% confidence interval (CI): 0.96-1.13,
      P=0.312; I2=0.0%; six trials; 18240 patients), regardless of whether the studies
      were of a multi-center (random-effects OR=1.04, 95% CI: 0.96-1.13, P=0.292;
      I2=0.0%) or single-center nature (random-effects OR=1.16, 95% CI: 0.28-4.71,
      P=0.839; I2=56.7%), or with low risk of bias (random-effects OR=1.04, 95% CI:
      0.94-1.16, P=0.445; I2=0.0%). In addition, the transfusion of fresher RBCs did
      not reduce the geometric mean duration of ICU stay (1.0% increase in geometric
      mean, 95% CI: -3.0 to 5.1%, P=0.638; I2=81.5%; four trials; 7550 patients) or the
      geometric mean duration of hospital stay (0.0% increase in geometric mean, 95%
      CI: -3.9 to 4.1%, P=0.957; I2=7.4%; four trials; 7550 patients) compared with the
      transfusion of older RBCs. CONCLUSIONS: The transfusion of fresher RBCs compared
      with older RBCs was not associated to better clinical outcomes in critically ill
      adults.

PMID- 30241933
TI  - Massive subcutaneous emphysema after thoracic trauma in a patient with pulmonary
      bullae.

PMID- 30241934
TI  - 2.8-A crystal structure of Escherichia coli YidC revealing all core regions,
      including flexible C2 loop.
AB  - YidC/Alb3/Oxa1 family proteins are involved in the insertion and assembly of
      membrane proteins. The core five transmembrane regions of YidC, which are
      conserved in the protein family, form a positively charged cavity open to the
      cytoplasmic side. The cavity plays an important role in membrane protein
      insertion. In all reported structural studies of YidC, the second cytoplasmic
      loop (C2 loop) was disordered, limiting the understanding of its role. Here, we
      determined the crystal structure of YidC including the C2 loop at 2.8 A
      resolution with R/Rfree = 21.8/27.5. This structure and subsequent molecular
      dynamics simulation indicated that the intrinsic flexible C2 loop covered the
      positively charged cavity. This crystal structure provides the coordinates of the
      complete core region including the C2 loop, which is valuable for further
      analyses of YidC.

PMID- 30241935
TI  - Erratum to "KLF5 promoted symmetric cell division in KRT5 positive keratinocytes
      through suppression of Notch1 expression" [Biochem. Biophys. Res. Commun. (2018
      Aug 6). pii: S0006-291X(18)31351-2. doi: 10.1016/j.bbrc.2018.06.039].

PMID- 30241936
TI  - The role and regulation of TMEM2 (transmembrane protein 2) in HYBID (hyaluronan
      (HA)-binding protein involved in HA depolymerization/ KIAA1199/CEMIP)-mediated HA
      depolymerization in human skin fibroblasts.
AB  - We have previously reported that HYBID (hyaluronan (HA)-binding protein involved
      in HA depolymerization/KIAA1199/CEMIP) is a specific HA-binding protein that is
      essential for HA depolymerization in skin and synovial fibroblasts. HA is
      incorporated into cells in the presence of HYBID and clathrin, degraded in
      endosomes, and excreted into the extracellular space. However, it is not yet
      clear whether HYBID itself catalytically cleaves HA. A recent report on
      transmembrane protein 2 (TMEM2)-a novel cell surface hyaluronidase-prompted us to
      investigate whether TMEM2 is essential for HYBID-mediated HA depolymerization. In
      the present study, we found that transforming growth factor beta 1 (TGF-beta1),
      which suppressed HA depolymerization with a concomitant decrease in HYBID
      expression, upregulated TMEM2 expression conversely in human skin fibroblasts.
      TMEM2 expression was not affected by histamine, which significantly increased HA
      depolymerization accompanied by an increase in HYBID expression. We confirmed a
      similar response in two other cell lines: KEL FIB keloid fibroblasts and HT1080
      fibrosarcoma cells. TGF-beta1 was the only inducer of TMEM2 expression among
      growth factors including epidermal growth factor (EGF), basic fibroblast growth
      factor (bFGF), and platelet-derived growth factor-BB (PDGF-BB), which suppressed
      HYBID expression. Moreover, HYBID knockdown completely suppressed HA
      depolymerization, whereas TMEM2 knockdown unexpectedly enhanced it. These
      findings clearly indicate that HYBID is indispensable, but TMEM2 is not involved
      in the HYBID-mediated HA depolymerization system as a catalytic hyaluronidase in
      human skin fibroblasts.

PMID- 30241937
TI  - Regulation of Gli2 stability by deubiquitinase OTUB2.
AB  - The transcription factor Gli2 plays crucial roles in the transduction of Hedgehog
      (Hh) signals, yet the mechanisms that control Gli2 degradation remain unclear.
      Here we have identified the eubiquitinating enzyme otubain2 (OTUB2) as a
      regulator of Gli2 protein degradation. We found that OTUB2 was
      coimmunoprecipitated with Gli2. Knockdown of OTUB2 decreased Gli2 protein level
      while the proteasome inhibitor MG-132 treatment restored Gli2 expression.
      Additionally, OTUB2 overexpression stabilized Gli2 protein in U2OS cells and
      extended the half-life of Gli2. We also found that knockdown of OTUB2 reduced
      deubiquitination of Gli2 in vivo. In vitro deubiquitination assay showed that
      ubiquitinated Gli2 was decreased by wild-type OTUB2 but not OTUB2 mutations. We
      also found that OTUB2 knockdown suppressed the ALP activity and the expression of
      the common markers BMP2 and RUNX2 during osteogenesis of MSCs in response to Shh
      and Smo agonists, which indicated OTUB2 may have effect on osteogenic
      differentiation by regulating Hh signaling.

PMID- 30241938
TI  - Reelin deficiency leads to aberrant lipid composition in mouse brain.
AB  - Reelin is a secreted protein essential for the development and function of the
      mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very
      low-density lipoprotein receptor, belong to the low-density lipoprotein receptor
      family, but it is not known whether Reelin is involved in the brain lipid
      metabolism. In the present study, we performed lipidomic analysis of the cerebral
      cortex of wild-type and Reelin-deficient (reeler) mice, and found that reeler
      mice exhibited several compositional changes in phospholipids. First, the ratio
      of phospholipids containing one saturated fatty acid (FA) and one docosahexaenoic
      acid (DHA) or arachidonic acid (ARA) decreased. Secondly, the ratio of
      phospholipids containing one monounsaturated FA (MUFA) and one DHA or ARA
      increased. Thirdly, the ratio of phospholipids containing 5,8,11-eicosatrienoic
      acid, or Mead acid (MA), increased. Finally, the expression of stearoyl-CoA
      desaturase-1 (SCD-1) increased. As the increase of MA is seen as an index of
      polyunsaturated FA (PUFA) deficiency, and the expression of SCD-1 is suppressed
      by PUFA, these results strongly suggest that the loss of Reelin leads to PUFA
      deficiency. Hence, MUFA and MA are synthesized in response to this deficiency, in
      part by inducing SCD-1 expression. This is the first report of changes of FA
      composition in the reeler mouse brain and provides a basis for further
      investigating the new role of Reelin in the development and function of the
      brain.

PMID- 30241939
TI  - YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced
      atrial fibrillation by modulating miR-384b/CACNA1C axis.
AB  - Recent years, the role of long non-coding RNAs (lncRNAs) in atrial fibrillation
      (AF) has been gradually elucidated. In the current study, we measured the
      expression of ten AF-related lncRNAs to do qRT-PCR analysis. LncRNA KCNQ1
      overlapping transcript 1 (KCNQ1OT1) was found to be significantly upregulated in
      AF model and Ang-II-induced mice heart. CACNA1C has been reported as a biomarker
      in atrial fibrillation. Here, we found that the expression pattern of CACNA1C was
      consistent with that of KCNQ1OT1. Electrophysiological study was conducted to
      demonstrate the effect of KCNQ1OT1 and CACNA1C on the Effective refractory period
      (ERP), interatrial conduction time (IACT), incidence of AF and AF duration of Ang
      II-induced mice heart. Mechanically, KCNQ1OT1 contributed to the upregulation of
      CACNA1C by binding with miR-384. Furthermore, YY1 could activate the
      transcription of KCNQ1OT1 and CACNA1C. In conclusion, the present study revealed
      that YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced
      atrial fibrillation by regulating miR-384/CACNA1C axis.

PMID- 30241940
TI  - Decreased expression of LATS1 correlates with astrogliosis after spinal cord
      injury.
AB  - Large tumor suppressor kinase 1 (LATS1) is a serine/threonine kinase of the AGC
      kinase family in mammals and involved in various biological processes, it is a
      key regulator of cell cycle progression. However, the role of LATS1 in central
      nervous system trauma is still unknown. In present study, we performed an acute
      spinal cord injury (SCI) model in adult rats and investigated the dynamic changes
      of LATS1 expression in the spinal cord. We found that LATS1 protein levels were
      significantly decreased at day 1 after injury. Meanwhile, double
      immunofluorescence staining showed these changes were striking in astrocytes,
      which were largely proliferated after SCI. In vitro, LATS1 overexpression
      inhibited astrocyte proliferation. Conversely, LATS1 depletion by siRNA promoted
      cell proliferation in primary astrocyte. Moreover, LATS1 overexpression reduced
      cyclin D1 expression and increased the expression of p27kip1. In addition, LATS1
      overexpression also promoted yes-associated protein 1 (YAP) phosphorylation. Our
      data suggested that LATS1 might play an important role in spinal cord injury and
      suppress astrogliosis through regulating the expression of cyclin D1, p27kip1 and
      p-YAP.

PMID- 30241941
TI  - CK2 downregulation induces senescence-associated heterochromatic foci formation
      through activating SUV39h1 and inactivating G9a.
AB  - Cellular senescence is an irreversible form of cell cycle arrest and senescent
      cells have a unique gene expression profile that is frequently accompanied by
      senescence-associated heterochromatic foci (SAHF). Here, we present evidence that
      CK2 downregulation induces trimethylation of histone H3 Lys 9 (H3K9me3),
      selective binding of HP1gamma to H3K9me3, formation of SAHF, and reduction of
      cyclin D1 expression in HCT116 and MCF-7 cells. CK2 downregulation-mediated
      H3K9me3 is associated with induction of H3K9 trimethylase SUV39h1 as well as
      reduction of H3K9 dimethylase G9a and GLP in cells. In addition, Pharmacological
      inhibition of SUV39h1 and G9a overexpression significantly attenuated induction
      of senescence-associated beta-galactosidase (SA-beta-gal) activity, H3K9me3 and
      SAHF formation in CK2-downregulated cells. Moreover, CK2 downregulation induced
      H3K9me3 in nematodes. Taken together, these results demonstrate that CK2
      downregulation leads to H3K9me3 and SAHF formation by increasing SUV39h1 and
      decreasing G9a.

PMID- 30241942
TI  - ERalpha is a negative regulator of PD-L1 gene transcription in breast cancer.
AB  - The programmed death-ligand 1 (PD-L1) expression by tumors results in potent
      antitumor immune suppression through binding to programmed death-1 (PD-1) on T
      cells and subsequent inhibition of T cells activity. Although recent pathological
      studies have shown that PD-L1 is actively expressed in certain ERalpha-negative
      breast cancer, little is known about whether ER signaling regulates PD-L1 gene
      expression. Here, we investigated the relationship between ERalpha and PD-L1 in
      breast cancer. Analysis of Comprehensive Cell Line Encyclopedia (CCLE) data
      showed that the average mRNA level of PD-L1 in ERalpha-positive breast cancer
      cell lines was significantly lower than that in ERalpha-negative breast cancer
      cell lines. E2 treatment inhibited PD-L1 mRNA expression in hormone-depleted
      ERalpha-positive MCF7 cells. Moreover, ectopic expression of ERalpha in triple
      negative MDA-MB-231 cells reduced PD-L1 mRNA and protein expression.
      Consistently, analysis of The Cancer Genome Atlas (TCGA) data revealed an inverse
      correlation between ERalpha and PD-L1 expression in ERalpha-positive breast
      cancer. Taken together, our results identify ERalpha as a negative regulator of
      PD-L1 gene transcription in breast cancer cells, suggesting that ERalpha loss-of
      function may facilitate the immune evasion of breast cancer cells via up
      regulation of PD-L1.

PMID- 30241943
TI  - Circ-SATB2 upregulates STIM1 expression and regulates vascular smooth muscle cell
      proliferation and differentiation through miR-939.
AB  - The prevention and treatment of coronary heart disease (CHD) is a difficult
      problem to be solved. More and more studies have found that circular RNAs
      (circRNAs) may play important roles in the development of CHD. Here detection of
      vascular smooth muscle cells (VSMCs) showed that circ-SATB2 and STIM1 were up
      regulated in proliferative VSMCs, while miR-939 were down-regulated. Circ-SATB2
      and miR-939 did not affect the expression of each other, but circ-SATB2 could
      promote while miR-939 inhibited the expression of STIM1 (a target gene of miR
      939). Circ-SATB2 overexpression could inhibit the expression of SM22-alpha
      (SM22alpha, a marker of contractile VSMCs), while the expression of SM22alpha was
      promoted by miR-939. STIM1 could promote cell proliferation and migration, and
      circ-SATB2 had similar effects, but its linear sequence had no such functions.
      MiR-939 had the opposite effects, could promote cell apoptosis and inhibit cell
      proliferation and migration, and siRNAs targeting circ-SATB2 had similar effects.
      When co-transfected with circ-SATB2 over-expression vector and miR-939 mimics or
      STIM1 siRNAs, the changes of cell proliferation, apoptosis and migration were not
      significant. Therefore, circ-SATB2 can regulate VSMC phenotypic differentiation,
      proliferation, apoptosis and migration by promoting the expression of STIM1. This
      discovery will provide a theoretical reference for exploring the role of circRNA
      in VSMCs and the pathogenesis of CHD.

PMID- 30241944
TI  - Spermidine ameliorates non-alcoholic fatty liver disease through regulating lipid
      metabolism via AMPK.
AB  - In this study, treatment of high-fat diet-induced obesity (DIO) C57BL/6J mice
      with spermidine decreased body weight and subcutaneous and visceral fat content,
      reversed the apparent hepatosteatosis, and reduced hepatic intracellular and
      serum triglyceride and total cholesterol concentrations. Moreover, spermidine
      treatment improved glucose tolerance and insulin sensitivity in DIO mice. The
      mechanism studies indicated that spermidine indeed increased the phosphorylation
      of hepatic AMP-activated protein kinase (AMPK), and inhibited the expression of
      lipogenic genes in vivo and in vitro. Moreover, these spermidine-mediated
      molecular effects were also abolished by compound C, an inhibitor of AMPK, in
      primary hepatocytes. In summary, spermidine protected against DIO-induced
      hepatosteatosis by decreasing lipogenic genes expression through an AMPK-mediated
      mechanism.

PMID- 30241945
TI  - Identification of biologically active delta-lactone eicosanoids as paraoxonase
      substrates.
AB  - The mammalian paraoxonases (PONs 1, 2 and 3) are a family of esterases that are
      highly conserved within and between species. They exhibit antioxidant and anti
      inflammatory activities. However, their physiological function(s) and native
      substrates are uncertain. Previous structure-activity relationship studies
      demonstrate that PONs have a high specificity for lipophilic lactones, suggesting
      that such compounds may be representative of native substrates. This report
      describes the ability of PONs to hydrolyze two bioactive delta-lactones derived
      from arachidonic acid, 5,6-dihydroxy-eicosatrienoic acid lactone (5,6-DHTL) and
      cyclo-epoxycyclopentenone (cyclo-EC). Both lactones were very efficiently
      hydrolyzed by purified PON3. PON1 efficiently hydrolyzed 5,6-DHTL, but with a
      specific activity about 15-fold lower than PON3. 5,6-DHTL was a poor substrate
      for PON2. Cyclo-EC was a poor substrate for PON1 and not hydrolyzed by PON2.
      Studies with the PON inhibitor EDTA and a serine esterase inhibitor indicated
      that the PONs are the main contributors to hydrolysis of the lactones in human
      and mouse liver homogenates. Studies with homogenates from PON3 knockout mouse
      livers indicated that >80% of the 5,6-DHTL and cyclo-EC lactonase activities were
      attributed to PON3. The findings provide further insight into the structural
      requirements for PONs substrates and support the hypothesis that PONs,
      particularly PON1 and PON3, evolved to hydrolyze and regulate a class of lactone
      lipid mediators derived from polyunsaturated fatty acids.

PMID- 30241946
TI  - CTP synthase knockdown during early development distorts the nascent vertebral
      column and causes fluid retention in multiple tissues in zebrafish.
AB  - CTP Synthase (CTPS) is a metabolic enzyme that is recognized as a catalyst for
      nucleotide, phospholipid and sialoglycoprotein production. Though the structural
      characteristics and regulatory mechanisms of CTPS are well-understood, little is
      known regarding the extent of its involvement during the early developmental
      stages of vertebrates. Zebrafish carries two CTPS genes, annotated as ctps1a and
      ctps1b. Phylogenetic analyses show that both genes had diverged from homologues
      in the ancestral Actinopterygii, Oreochromis niloticus. Conservation of common
      CTPS-catalytic regions further establishes that both proteins are likely to be
      functionally similar to hsaCTPS. Here, we show that ctps1a is more critical
      throughout the initial period of embryonic development than ctps1b. The effects
      of concurrent partial knockdown are dependent on ctps1a vs ctps1b dosage ratios.
      When these are equally attenuated, abnormal phenotypes acquired prior to the
      pharyngula period disappear in hatchlings (48hpf); however, if either gene is
      more attenuated than the other, these only become more pronounced in advanced
      stages. Generally, disruption to normal ctps1a or ctps1b expression levels by
      morpholinos culminates in the distortion of the early spinal column as well as
      multiple-tissue oedema. Other effects include slower growth rates, increased
      mortality rates and impaired structural formation of the young fish's
      extremities. Embryos grown in DON, a glutamine-analogue drug and CTPS antagonist,
      also exhibit similar characteristics, thus strengthening the validity of the
      morpholino-induced phenotypes observed. Together, our results demonstrate the
      importance of CTPS for the development of zebrafish embryos, as well as a
      disparity in activity and overall importance amongst isozymes.

PMID- 30241947
TI  - Skeletal muscle secretion of IL-6 is muscle type specific: Ex vivo evidence.
AB  - Emerging evidence indicates that skeletal muscle possesses endocrine function to
      secret myokines. Interleukin 6 (IL-6) is a well-characterized myokine that is
      involved in regulation of metabolism and muscle function. Metabolism type and
      contractile dynamics vary in different muscle types. It is not clear, however, if
      IL-6 secretion differs in different muscle types. In this study, we first
      established an ex vivo approach to test the inducible muscle secretion. Freshly
      isolated muscles were incubated in Krebs solution at 37  degrees C with oxygen
      supply. Secreted IL-6 in the incubation media was measure using Western blot and
      ELISA assay. We first confirmed that the IL-6 release was inducible by treating
      the incubated muscle with a cytokine stimulant. We demonstrated that
      physiological temperature (37  degrees C) and O2 supply were essential for the
      induction of IL-6 release from the incubated muscle, suggesting it is a
      controlled secretion rather than a spontaneous leak. Using this approach, we
      found that IL-6 release was only inducible from soleus muscle but not EDL muscle.
      We further showed that IL-6 protein level was higher in slow oxidative muscle
      fibers. Moreover, we showed that EDL, although lacks of IL-6 release, surely has
      inducible secretory function that had different secretory pattern from soleus.

PMID- 30241948
TI  - Positivity of dengue and chikungunya among Crimean-Congo hemorrhagic fever
      negative cases in India: 2013-2016.

PMID- 30241949
TI  - Prenatal genetic carrier screening in the genomic age.
AB  - The Society for Maternal-Fetal Medicine, American College of Obstetricians and
      Gynecologists (ACOG), and American College of Medical Genetics and Genomics
      (ACMG) held a workshop entitled "Prenatal Genetic Testing" on January 25, 2017 to
      address several questions arising from the increasing implementation of
      preconception and prenatal expanded carrier screening (ECS). ECS allows for
      identification of a greater number of genetic sequencing changes (not all of
      which cause disease) and simultaneous testing for an increased number of genetic
      conditions without limitation to specific ethnic groups. The workshop
      participants reached consensus on the following: ethnicity based testing cannot
      be completely abandoned in favor of panethnic ECS; the specific approach to
      screening should be a patient's choice and not driven solely by provider
      preference; organizations should work to develop a framework for vetting
      conditions that should be reported on ECS panels; compared with prenatal
      screening, preconception screening is ideal and, at this time, due to the costs
      and the need for timeliness associated with prenatal screening posttest
      counseling and testing, that when ECS is offered it should be presented as a
      preconception option; preconception and prenatal panels should be identical
      across the spectrum of patients, including those undergoing assisted
      reproduction; adult-onset conditions should not be included on ECS panels;
      partners should be offered next-generation sequencing to identify rare variants
      when the first partner screened is determined to be a carrier; re-screening in
      subsequent pregnancies is not indicated, despite the potential for expansion of
      carrier screening conditions and variants; and more education about ECS for
      providers and patients is necessary to implement prenatal carrier screening in a
      responsible way.

PMID- 30241950
TI  - Industry perspectives on prenatal genetic testing.
AB  - Until recent years, prenatal genetic tests have been almost exclusively developed
      and implemented by academic physicians and laboratories. In the last several
      years, industry has led the development of novel prenatal genetic tests, funded
      clinical trials and implemented these tests into clinical practice. That these
      efforts have been driven by industry has raised questions about diagnostics
      development regulations, consistency in reporting of results, and management of
      potential conflicts of interest. In this article, these topics are addressed from
      an industry perspective. While commercial laboratories may have the resources to
      develop and offer novel genetic tests, collaboration with healthcare providers is
      crucial for appropriate, effective, and efficient utilization of such tests.

PMID- 30241951
TI  - Simultaneous low-frequency deep brain stimulation of the substantia nigra pars
      reticulata and high-frequency stimulation of the subthalamic nucleus to treat
      levodopa unresponsive freezing of gait in Parkinson's disease: A pilot study.
AB  - INTRODUCTION: Experimental studies suggest that low-frequency (LF) (63 Hz) deep
      brain stimulation (DBS) of the substantia nigra pars reticulata (SNr) could be
      useful to regulate gait disorders refractory to medical treatment in Parkinson's
      disease (PD). The SNr neurons could act as high-frequency (HF) pacemakers within
      locomotor control systems. Currently, no specific therapies can treat gait
      disorders in PD with insufficient response to dopaminergic treatment. OBJECTIVE:
      To investigate whether LF-SNr-DBS combined with standard HF stimulation of the
      subthalamic nucleus (STN) is clinically relevant in improving gait disorders that
      no longer respond to levodopa in PD patients, compared with HF-STN or LF-SNr
      stimulation alone. METHODS: Patients received LF-SNr or HF-STN stimulation alone
      or combined (COMB) stimulation of both nuclei (crossover design). The nucleus to
      be stimulated was randomly assigned and clinical evaluations performed by a
      blinded examiner after three months follow-up for each. Clinical assessment
      included the Freezing of Gait questionnaire, Tinetti Balance and Walking
      Assessing tool, and Unified Parkinson's Disease Rating. RESULTS: We included six
      patients (mean age 59.1 years, disease duration 16.1 years). All patients
      suffered motor fluctuations and dyskinesias. The best results were obtained with
      COMB in four patients (who preferred and remained with COMB over 3 years of
      follow-up) and with HF-STN in two patients. SNr stimulation alone did not produce
      better results than COMB or STN in any patient. CONCLUSION: COMB and HF-STN
      stimulation improved PD-associated gait disorders in this preliminary case
      series, sustained over time. Further multicenter investigations are required to
      better explore this therapeutic option.

PMID- 30241952
TI  - Will the kidney function be reduced in patients with renal cell carcinoma
      following laparoscopic partial nephrectomy? Baseline eGFR, warm ischemia time,
      and RENAL nephrometry score could tell.
AB  - OBJECTIVES: To describe the natural history of kidney function following partial
      nephrectomy (PN) for patients with renal cell carcinoma (RCC), and to identify
      independent predictors of whether patients with RCC will retain renal function
      unchangeable or even increased and develop functional impairment of ?25% post-PN.
      PATIENTS AND METHODS: We performed a retrospective analysis of 337 cases
      involving patients diagnosed with RCC of pT1-2N0M0 who underwent laparoscopic PN,
      the primary endpoints included the stabilization or increase in postoperative
      estimated glomerular filtration rate (eGFR) compared to the preoperative level
      and eGFR impairment of ?25% following surgery. We plotted the trajectory of each
      patient's eGFR measurement starting from their first postoperative day to the
      last follow-up time post-PN and used moving average method to look at trends of
      eGFR changing. A logistic regression model was then applied to identify
      associations between clinical and surgical characteristics with eGFR outcomes.
      RESULTS: Patients were of an average age of 51.4 years and all were Chinese
      descent. The cohort was also primarily male (69.1%). One hundred ninety seven
      (58.5%) had eGFR ?90 ml/min/1.73 m2, while 140 (41.5%) had an eGFR of 60 to 90
      ml/min/1.73 m2 prior to the operation. All patients underwent minimally invasive
      PN with warm ischemia, with 64.1% (216/337) receiving laparoscopic surgery, and
      35.9% (121/337) receiving robot-assisted laparoscopic surgery. On average,
      patients experienced a mean eGFR decrease of 23.8% immediately post-PN, followed
      by a slight increase and stabilization, with a mean 15.5% decline after 1 year.
      Twenty four percent (81/337) experienced GFR impairment of ?25% over a median
      10.0-month follow-up time period, while 29.1% (99/337) patients retained eGFR
      unchangeable or increased post-PN. And higher preoperative eGFR, longer warm
      ischemia time, and more complexity lesions (higher renal nephrometry score ) were
      found to be independently associated with higher chance of functional impairment
      of ?25% and lower chance of eGFR stabilization post-PN. CONCLUSION: Although,
      majority of patients experienced decline of renal function post-PN, functional
      outcomes of eGFR unchangeable and increased were also seen, and baseline total
      eGFR, WIT as well as RENAL nephrometry score were determined to be independent
      predictors of those renal functional outcomes.

PMID- 30241953
TI  - Prostate cancer tissues with positive TMPRSS2-ERG-gene-fusion status may display
      enhanced nerve density.
AB  - Innervation of prostate cancer (CaP) tissue favors tumor progression and
      metastasis but the regulation of innervation in CaP is unclear. The oncogenic
      transcription factor ERG is commonly induced by a typical TMPRSS2-ERG (TE) gene
      fusion in CaP and may affect innervation. Here, we analyzed whether nerve density
      of CaP tissue is related to TE status or perineural infiltration status of CaP
      tissue. In parallel, we measured several members of the
      neuropilin/plexin/semaphorin family (NRP, PLXN, and SEMA) as possible targets
      mediating innervation. The TE-gene-fusion status was determined at the mRNA level
      in CaP tissues by nested RT-PCR. Transcript levels were analyzed by quantitative
      RT-PCR in CaP tissue or cell line homogenate. ERG was analyzed by immunostaining,
      and the nerve density was evaluated by immunostaining for PGP9.5 and axonal
      neurofilament. Data were analyzed by correlation (Spearman), linear regression,
      Mann-Whitney U test, and contingency table analyses. TE-positive (TE-1) vs. TE
      negative (TE-0) CaP tissues displayed significantly enhanced ERG-mRNA levels (TE
      0: -4.183; TE-1: -2.994, P < 0.001) and ERG immunostaining (Erg-IH score; TE-0:
      0.4211; TE-1: 1.391; P < 0.0001). Notably, the nerve density was significantly
      increased in CaP tissue samples with positive TE status compared to negative TE
      status (TE-0, ND score = 1.5; TE-1, ND score = 2.0; P <0.01). NRP1, NRP2, PLXNA2,
      PLXNB1, SEMA3A, and SEMA4B mRNAs were detectable in CaP tissues and CaP cell
      lines at quite heterogeneous levels. In CaP tissues, we observed significant
      positive correlations of ERG with NRP2, PLXNA2, PLXNB1, and SEMA4B. TE-positive
      CaP tissues displayed enhanced nerve density. ERG correlated with some
      NRP/PLXN/SEMA components suggesting possible regulatory relevance of ERG for CaP
      innervation.

PMID- 30241954
TI  - Seniority of primary care physicians is associated with a decrease in PSA
      ordering habits in the years surrounding the United States Preventative Services
      Task Force recommendation against PSA screening.
AB  - INTRODUCTION: The United States Preventative Services Task Force recommendation
      against prostate-specific antigen (PSA) screening came in 2012, a time when many
      new primary care providers (PCPs) had been trained in the PSA screening era. We
      examined the differential effect of the recommendation on PCPs' PSA screening by
      physician seniority and evaluated the impact of their individual stated opinions
      on their screening practices. METHODS: We reviewed 54,684 PCP-directed PSA orders
      within a tertiary care academic institution from January 2010 to July 2015.
      Relative proportions of PSA orders per overall unique male ambulatory clinic
      volume were assessed for the periods of January 1, 2010 to December 31, 2011
      (first period) and January 1, 2013 to July 31, 2015 (second period). A survey was
      subsequently sent to providers in the cohort assessing their attitudes toward the
      United States Preventative Services Task Force recommendation and responses were
      compared to physician seniority and actual PSA ordering habits. RESULTS: Of 88
      total PCPs assessed, 22 met criteria for inclusion. Overall unique male
      nononcology care patients were 88,558 for the first period and 140,173 for the
      second period. Overall proportion of unique male patients screened did not change
      and proportion of overall unique male patients screened vs. time since residency
      demonstrated a significant negative trend (R2 = 0.308, P = 0.007, slope of trend
      line -0.000005). A subsequent survey revealed no correlation of any aspect of the
      questionnaire with actual real-world screening practice but did note a
      paradoxical positive association between physician seniority and stated PSA use.
      CONCLUSION: From January 2010 to July 2015 PSA screening did not change greatly
      for providers in continuous practice throughout the period. Time since residency
      completion was significantly associated with screening proportionally fewer men.
      Provider opinion did not appear to have a strong influence on actual physician
      practice. These findings further inform future efforts to alter PSA screening.

PMID- 30241955
TI  - Efficacy and Safety of Combined Therapy With Synthetic Disease-modifying
      Antirheumatic Drugs in Rheumatoid Arthritis: Systematic Literature Review.
AB  - OBJECTIVE: 1) To systematically and critically review the evidence of combined
      therapy with synthetic disease-modifying antirheumatic drugs (DMARD) in
      rheumatoid arthritis (RA); 2) To design practical recommendations on their use.
      METHODS: A systematic literature review (SLR) was performed with a sensitive
      bibliographic search strategy in Medline, EMBASE and Cochrane Library. We
      selected randomized clinical trials that analyzed the efficacy and/or safety of
      1) combined therapy of synthetic compared with sequential therapy of synthetic
      DMARD in early RA; and 2) combination of methotrexate+leflunomide or triple
      therapy with synthetic DMARD in established RA refractory to synthetic DMARD. Two
      reviewers made the first selection by title and abstract and 11 performed the
      selection after detailed review of the articles and data collection. The quality
      of the studies was evaluated with the Jadad scale. Based on the results, related
      recommendations were agreed upon in a nominal group meeting. RESULTS: Ultimately,
      no articles were included in the SLR. The analysis of the reviewed articles
      demonstrated the effectiveness of the treatment with synthetic DMARD following a
      "treat to target" strategy in early RA patients, and of combination therapy of
      synthetic DMARD in established RA refractory to synthetic DMARD. This resulted in
      6 recommendations concerning combination therapy with synthetic DMARD.
      CONCLUSIONS: These recommendations aim to facilitate decision-making with the use
      of combined therapy with DMARD in RA.

PMID- 30241957
TI  - Putting it all together: Options for intractable epilepsy: An updated algorithm
      on the use of epilepsy surgery and neurostimulation.
AB  - For drug-resistant epilepsy, nonpharmacologic treatments should be considered
      early rather than late. Of the nondrug treatments, only resective surgery can be
      curative. Neurostimulation is palliative, i.e., not expected to achieve a seizure
      free outcome. While resective surgery is the goal, other options are necessary
      because the majority of patients with drug-resistant epilepsy are not surgical
      candidates, and others have seizures that fail to improve with surgery or have
      only partial improvement but not seizure freedom. Neurostimulation modalities
      include vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and
      deep brain stimulation (DBS), each with its own advantages, disadvantages, and
      side effects. In most scenarios, determined by noninvasive evaluation, especially
      EEG and MRI, several strategies are reasonable. For focal epilepsies, the choices
      are between resective surgery, with or without intracranial EEG, and all three
      modalities of neurostimulation. In situations where resective surgery is likely
      to result in seizure freedom, such as mesiotemporal lobe epilepsy or lesional
      focal epilepsy, resection (standard, laser, or radiofrequency) is preferred. For
      difficult cases like extratemporal nonlesional epilepsies, neurostimulation
      offers a less invasive option than resective surgery. For generalized and
      multifocal epilepsies, VNS is an option, RNS is not, and DBS has only limited
      evidence. This article is part of the Special Issue "Neurostimulation for
      Epilepsy".

PMID- 30241956
TI  - The impact of binge eating behavior on lithium- and quetiapine-associated changes
      in body weight, body mass index, and waist circumference during 6 months of
      treatment: Findings from the bipolar CHOICE study.
AB  - BACKGROUND: Lithium and quetiapine can cause weight gain, but their comparative
      longer term anthropometric effects are unknown, as are the potential moderating
      effects of baseline binge-eating (BE) behavior. METHODS: We assessed 6 month
      changes in body weight, body mass index (BMI) and waist circumference in 482
      adults with DSM-IV bipolar disorders who participated in a comparative
      effectiveness study of lithium and quetiapine with evidence-based adjunctive
      treatment (Bipolar CHOICE). Anthropometric measurements were obtained at
      baseline, and at 2, 4, 6, 8, 12, 16, 20, and 24 weeks. BE behavior was defined as
      affirmative responses to MINI items M1 and M3 at baseline. Data were analyzed
      using a mixed model repeated measures approach, adjusted for baseline values of
      dependent measures. RESULTS: On average, body weight and BMI increased over 6
      months with lithium and quetiapine. However, those treated with quetiapine
      experienced greater increases from baseline in body weight (peak change, + 3.6
      lbs. vs. + 1.4 lbs.) and BMI (peak change, + 0.6 kg/m2 vs. + 0.3 kg/m2), starting
      at 2 weeks (group x time, F8,3052 = 2.9, p = 0.003 for body weight, F8,3052 =
      3.0, p = 0.002 for BMI). Significant increases in waist circumference were
      observed only with quetiapine. The relationship between drug treatment and
      changes in body weight (group x time x binge eating status, F1,2770 = 2.0, p =
      0.002), BMI (F1,2767 = 2.0, p = 0.002), and waist circumference (women only,
      F25,1621 = 2.9, p < 0.0001) were moderated by BE behavior. The largest increases
      over 24 weeks in body weight and BMI, and waist circumference in women, occurred
      for quetiapine-treated patients with baseline binge-eating, relative to
      quetiapine-treated patients without binge eating and lithium-treated patients
      with or without baseline binge-eating. LIMITATIONS: Bipolar CHOICE was not
      designed to study anthropometric outcomes. CONCLUSIONS: Greater changes in body
      weight, BMI, and waist circumference occurred with quetiapine- versus lithium
      based treatment over 6 months of treatment. The effects of study drugs on these
      anthropometric measures were moderated by BE behavior at baseline.

PMID- 30241958
TI  - MIF Matters: The Macrophage Migration Inhibitory Factor and Kidney Injury.

PMID- 30241959
TI  - Nephrotic Syndrome With Mutations in NPHS2: The Role of R229Q and Implications
      for Genetic Counseling.
AB  - Mutations in the NPHS2 gene, which encodes the podocyte slit diaphragm protein
      podocin, cause autosomal recessive steroid-resistant nephrotic syndrome (Online
      Mendelian Inheritance in Man [OMIM] #600995). Basic research and clinical studies
      have provided important insights about genotype-phenotype correlations. This
      knowledge allows personalized genetic (risk) counseling and should lead to
      changes in the advice given to patients. A patient who carries the R229Q variant
      (which has a high allele frequency of 3.7% in the European population) in
      combination with a pathogenic variant in exon 7 or 8 is at high risk for
      developing nephrotic syndrome that may not manifest before adulthood, whereas a
      patient with 2 pathogenic variants will develop congenital or childhood-onset
      nephrotic syndrome. In contrast, a patient who carries the R229Q variant in
      combination with a pathogenic variant in exons 1 to 6 is unlikely to develop
      nephrotic syndrome. In this article, we review the emerging knowledge about the
      NPHS2 gene and translate these findings from the bench to practical advice for
      the clinical bedside.

PMID- 30241960
TI  - Single-Cell RNA Sequencing of the Adult Mouse Kidney: From Molecular Cataloging
      of Cell Types to Disease-Associated Predictions.

PMID- 30241961
TI  - Probiotics and the prevention of necrotizing enterocolitis.
AB  - BACKGROUND: Immaturity of the host immune system and alterations in the
      intestinal microbiome appear to be key factors in the pathogenesis of necrotizing
      enterocolitis (NEC). The aim of this paper is to weigh the evidence for the use
      of probiotics to prevent NEC in premature infants. METHODS: Animal studies,
      randomized controlled trials, observational cohort studies and meta-analyses
      involving administration of probiotic products for the prevention of NEC were
      reviewed. This review of the evidence summarizes the available preclinical and
      clinical data. RESULTS: In animal models probiotic microbes alter the intestinal
      microbiome, decrease inflammation and intestinal permeability and decrease the
      incidence and severity of experimental NEC. In randomized, placebo-controlled
      trials and cohort studies of premature infants, probiotic microbes decrease the
      risk of NEC, death and sepsis. CONCLUSION: Evidence is strong for the prevention
      of NEC with the use of combination probiotics in premature infants who receive
      breast milk. The potential risks and benefits of probiotic administration to
      premature infants should be carefully reviewed with parents. TYPE OF STUDY:
      Therapeutic. LEVEL OF EVIDENCE: I.

PMID- 30241962
TI  - Too much of a bad thing: Discharge opioid prescriptions in pediatric appendectomy
      patients.
AB  - BACKGROUND: Opioid misuse is a public health crisis in the United States. This
      study aimed to evaluate the discharge opioid prescription practices for pediatric
      simple appendectomy patients. METHODS: A retrospective review of pediatric
      appendectomy patients at a tertiary children's hospital was conducted from
      October 2016 to January 2018. Only patients with simple appendicitis were
      included. Written opioid prescriptions were found in the electronic medical
      record (EMR) or through a statewide prescription monitoring database. All dosing
      data were converted to oral morphine equivalents (OMEs). Analysis of variance and
      logistic regression were used. RESULTS: During the study, 590 patients underwent
      appendectomy, of which 371 (62.9%) were diagnosed as having simple acute
      appendicitis. The majority of patients were prescribed an opioid analgesic
      (62.5%). Demographics were similar between those who received opioids and those
      who did not. The OME prescribed per day (range 0.2 to 3.4 mg/kg/day) was highly
      variable as was duration of prescription (1 to 30 days). Odds of emergency
      department visit were 3.3 times higher (95% CI 1.3-8.2) in those who received
      opioids. CONCLUSION: Postdischarge prescription practices for pediatric
      appendectomy are highly variable. Two-thirds of patients who received narcotics
      had a higher rate of complications. Greater scrutiny is required to optimize
      opioid stewardship. TYPE OF STUDY: Retrospective comparative study. LEVEL OF
      EVIDENCE: Level III.

PMID- 30241963
TI  - Current surgical practice in pediatric ulcerative colitis: A systematic review.
AB  - BACKGROUND: Surgical management of adult ulcerative colitis (UC) is well-studied,
      but not readily applicable to children. Restorative proctocolectomy with ileal
      pouch-anal anastomosis (RPC-IPAA), performed as one-, two-, or three-stage
      procedure, is preferred in pediatric patients with adequate anal sphincter
      function. PURPOSE: METHODS: Systematic review of Cochrane Register of Controlled
      Trials, PubMed, and EMBASE databases was conducted (January 1987-December 2016),
      in accordance with PRISMA. RESULTS: Twelve retrospective studies were identified
      (568 patients total); 31, 334, and 203 patients underwent one-, two-, and three
      stage procedures, respectively. Median study size was 31 patients (range 10-202),
      median age was 13 years (range 2-21), median follow-up was 4 years (range 0.08
      16). Postoperative complications included pouchitis, bowel obstruction,
      stricture, fistula, pouch failure, anastomotic leak, and wound infections.
      Calcineurin inhibitor usage improved pediatric ulcerative colitis activity index
      (PUCAI) score. Higher PUCAI scores correlated with likelihood of staged
      procedures. Number of stages did not restrict quality of life. CONCLUSIONS:
      Paucity of data exists, comparing preoperative factors leading to staged
      procedures in pediatric UC. This systematic review identifies an area for future
      studies. LEVEL OF EVIDENCE: II.

PMID- 30241964
TI  - Gender differences in improvement of older-person-specific quality of life after
      hearing-aid fitting.
AB  - BACKGROUND: Age-related hearing loss is the third most common reason for
      disability in the world and has a significant impact on quality of life (QoL)
      amongst older adults. OBJECTIVE: To determine how the QoL assessment in older
      person-specific domains differs between older men and women with age-related
      hearing loss before and after hearing-aid fittings. METHODS: The present study
      was carried out with 105 hearing-impaired outpatients (aged >= 60 years) before
      and after hearing-aid fittings at the University Hospital Olomouc, Czech
      Republic. The instrument used was the World Health Organization Quality of Life
      Older Adults module (WHOQOL-Old). It was completed before hearing-aid fittings
      and after the first check-up hearing-aid adjustment. The Wilcoxon paired test
      multiple logistic regression was used to evaluate changes in the QoL after
      hearing-aid fittings. The distributions of men a women into three subgroups,
      improved, unchanged, and worsened in each domain, were compared using Fisher's
      exact test. RESULTS: A significant QoL improvement when fitting a hearing-aid in
      the area of Sensory abilities was confirmed in both men and women (p < 0.001). In
      Autonomy, a significant improvement was recorded only amongst men (p = 0.010). In
      Past, present and future activities and Social participation, a significant
      improvement was only recorded amongst women (p = 0.029; p = 0.001). Significant
      differences were revealed between men and women in changes for Sensory Abilities
      (p = 0.019), Social Participation (p = 0.036) and Intimacy (p = 0.002).
      CONCLUSIONS: The findings of this study suggest that there are gender differences
      in QoL improvement amongst people with age-related hearing loss after hearing-aid
      fitting.

PMID- 30241965
TI  - Role of Elective Nodal Irradiation in Patients With ypN0 After Neoadjuvant
      Chemotherapy Followed by Breast-Conserving Surgery (KROG 16-16).
AB  - BACKGROUND: Given the lack of established indications for elective nodal
      irradiation (ENI) in ypN0 patients after neoadjuvant chemotherapy (NAC) and
      breast-conserving surgery (BCS), we set out to investigate the role of ENI in
      ypN0 patients according to subtype and pathologic complete remission (pCR)
      status. PATIENTS AND METHODS: We analyzed 261 patients who received NAC followed
      by BCS and adjuvant radiotherapy in 13 institutions of the Korean Radiation
      Oncology Group from 2005 to 2011. The tumors were classified into one of 3
      subtypes: luminal (estrogen receptor positive or progesterone receptor positive
      and HER2 negative), HER2 (HER2 positive), or triple negative (estrogen receptor,
      progesterone receptor, and HER2 negative). We compared locoregional control
      (LRC), disease-free survival (DFS), and overall survival (OS) according to ENI in
      different subgroups generated by the subtype and pCR statuses. RESULTS: In all
      patients, the 5-year LRC, DFS, and OS rates were 96.0%, 91.0%, and 96.8%,
      respectively. In all patients, axillary lymph node dissection was found to be the
      only favorable factor for LRC (P = .023) and DFS (P = .001). Age >= 50 years (P =
      .027), negative resection margin (P = .002), and axillary lymph node dissection
      (P = .002) were all favorable factors for OS. ENI did not affect LRC, DFS, or OS.
      Subgroup analysis by tumor subtype and pCR showed that ENI was not associated
      with greater LRC or DFS in any subgroups. CONCLUSION: In ypN0 patients after NAC
      and BCS, ENI did not improve LRC or survival, regardless of subtype or primary
      tumor response. This result should be verified through larger prospective trials.

PMID- 30241966
TI  - Individualized Prediction of Menses Recovery After Chemotherapy for Early-stage
      Breast Cancer: A Nomogram Developed From UNICANCER PACS04 and PACS05 Trials.
AB  - BACKGROUND: The likelihood of menses recovery varies greatly in premenopausal
      patients receiving adjuvant chemotherapy for breast cancer. Quantifying this
      probability for each patient could better inform the chemotherapy discussion and
      individualize fertility counseling. We performed a pooled analysis of the PACS04
      and PACS05 adjuvant randomized trials to develop a nomogram to estimate the
      probability of menses recovery at 3, 6, and 18 months after the end of adjuvant
      chemotherapy. PATIENTS AND METHODS: Women who were premenopausal and aged <= 50
      years at randomization in the PACS04 and PACS05 trials were included in the
      present analysis. The primary endpoint was the probability of menses recovery
      within 18 months of chemotherapy completion. Multivariable Cox proportional
      hazards regression was used to estimate the association of each variable with the
      likelihood of menses resumption. A nomogram was developed to predict menses
      recovery at different intervals. RESULTS: The factors associated with menses
      recovery were assessed for 1210 patients. At a median follow-up of 90 months
      (range, 3-189 months), 342 of 1210 patients (28.2%) had recovered menses. The
      probability of menses recovery at 18 months was 25.5% (range, 23.0%-27.9%). After
      backward elimination, age, final body mass index, type of chemotherapy, and
      hormone therapy were selected to build the nomogram to predict the probability of
      menstrual resumption at 3, 6, and 18 months after chemotherapy. CONCLUSION: An
      accurate and individualized prediction of menses recovery is feasible for
      premenopausal patients eligible for adjuvant chemotherapy for early-stage breast
      cancer. Our nomogram will be externally validated in a large prospective cohort.

PMID- 30241967
TI  - Multispectral Optoacoustic Tomography in Assessment of Breast Tumor Margins
      During Breast-Conserving Surgery: A First-in-human Case Study.

PMID- 30241969
TI  - The Generic Facet of Hox Protein Function.
AB  - Hox transcription factors are essential to promote morphological diversification
      of the animal body. A substantial number of studies have focused on how Hox
      proteins reach functional specificity, an issue that arises from the fact that
      these transcription factors control distinct developmental functions despite
      sharing similar molecular properties. In this review, we highlight that, besides
      specific functions, for which these transcription factors are renowned, Hox
      proteins also often have nonspecific functions. We next discuss some emerging
      principles of these generic functions and how they relate to specific functions
      and explore our current grasp of the underlying molecular mechanisms.

PMID- 30241968
TI  - Deeply-learnt damped least-squares (DL-DLS) method for inverse kinematics of
      snake-like robots.
AB  - Recently, snake-like robots are proposed to assist experts during medical
      procedures on internal organs via natural orifices. Despite their well-spelt
      advantages, applications in radiosurgery is still hindered by absence of suitable
      designs required for spatial navigations within clustered and confined parts of
      human body, and inexistence of precise and fast inverse kinematics (IK) models.
      In this study, a deeply-learnt damped least squares method is proposed for
      solving IK of spatial snake-like robot. The robot's model consists of several
      modules, and each module has a pair of serial-links connected with orthogonal
      twists. For precise control of the robot's end-effector, damped least-squares
      approach is used to minimize error magnitude in a function modeled over
      analytical Jacobian of the robot. This is iteratively done until an apt joint
      vector needed to converge the robot to desired positions is obtained. For fast
      control and singularity avoidance, a deep network is built for prediction of
      unique damping factor required for each target point in the robot's workspace.
      The deep network consists of 11 x 15 array of neurons at the hidden layer, and
      deeply-learnt with a huge dataset of 877,500 data points generated from workspace
      of the snake robot. Implementation results for both simulated and actual
      prototype of an eight-link model of the robot show the effectiveness of the
      proposed IK method. With error tolerance of 0.01 mm, the proposed method has a
      very high reachability measure of 91.59% and faster mean execution time of 9.20
      (+/-16.92) ms for convergence. In addition, the method requires an average of
      33.02 (+/-39.60) iterations to solve the IK problem. Hence, approximately 3.6
      iterations can be executed in 1 ms. Evaluation against popularly used IK methods
      shows that the proposed method has very good performance in terms of accuracy and
      speed, simultaneously.

PMID- 30241970
TI  - In-vitro validation of 4D flow MRI measurements with an experimental pulsatile
      flow model.
AB  - PURPOSE: The purpose of this study was to assess the precision of four
      dimensional (4D) phase-contrast magnetic resonance imaging (PCMRI) to measure
      mean flow and peak velocity (Vmax) in a pulsatile flow phantom and to test its
      sensitivity to spatial resolution and Venc. MATERIAL AND METHODS: The pulsatile
      flow phantom consisted of a straight tube connected to the systemic circulation
      of an experimental mock circulatory system. Four-dimensional-PCMR images were
      acquired using different spatial resolutions (minimum pixel size: 1.5*1.5*1.5mm3)
      and velocity encoding sensitivities (up to three times Vmax). Mean flow and Vmax
      calculated from 4D-PCMRI were compared respectively to the reference phantom flow
      parameters and to Vmax obtained from two-dimensional (2D)-PCMRI. RESULTS: 4D-PCI
      measured mean flow with a precision of -0.04% to+5.46%, but slightly
      underestimated Vmax when compared to 2D-PCMRI (differences ranging from -1.71% to
      -3.85%). 4D PCMRI mean flow measurement was influenced by spatial resolution
      (P<0.001) with better results obtained with smaller voxel size. There was no
      effect of Venc on mean flow measurement. Regarding Vmax, neither spatial
      resolution nor Venc did influence the precision of the measurement. CONCLUSION:
      Using an experimental pulsatile flow model 4D-PCMRI is accurate to measure mean
      flow and Vmax with better results obtained with higher spatial resolution. We
      also show that Venc up to 3 times higher than Vmax may be used with no effect on
      these measurements.

PMID- 30241971
TI  - Influence of GeneXpert MRSA/SA test implementation on clinical outcomes of
      Staphylococcus aureus bacteremia - a before-after retrospective study.
AB  - Use of GeneXpert MRSA/SA in diagnostic algorithms of Staphylococcus aureus
      bacteremia may influence both patients' clinical outcomes and antibiotic
      stewardship. We evaluated these outcomes in a retrospective cohort before
      (1/6/2015-31/5/2016) and after (1/6/2016-31/8/2017) the introduction of the test
      in adult patients with Gram-positive cocci in clusters in blood cultures. We
      included 254 patients (125 preintervention, 129 postintervention). No significant
      difference in 30-day mortality or clinical success was demonstrated between
      periods. Appropriate antibiotic therapy rates were significantly higher in the
      postintervention group, and vancomycin use was significantly reduced (80.6% vs
      53.6%, P < 0.01; 2.3+/-0.38 vs 2.98+/-1.02 defined daily doses/100 patient days,
      P = 0.026, respectively). Appropriate beta-lactam use was also significantly
      higher (56.7% postintervention vs 23.1% preintervention, P < 0.01). Use of
      GeneXpert MRSA/SA test has a positive effect on antibiotic stewardship measures,
      though it has no significant effect on clinical outcomes including mortality in
      this fatal infection.

PMID- 30241972
TI  - Variation and Trends in Antidepressant Prescribing for Men Undergoing Treatment
      for Nonmetastatic Prostate Cancer: A Population-based Cohort Study.
AB  - : Psychological distress is prevalent among men with prostate cancer (PCa).
      However, the variation in antidepressant use among individuals throughout the
      survivorship period is unknown. We sought to examine the variation and trends in
      receipt of antidepressants after PCa treatment, among patients with nonmetastatic
      PCa. Using population-based linked administrative data, we identified men >=66 yr
      old who underwent surgery (n=4952), radiotherapy (n=4994), or surveillance
      (n=2136), and these men were matched to general population controls (n=57127).
      One year prior to PCa treatment, 7.7% of men received an antidepressant
      prescription, which increased to 10.5% in the year after treatment. In difference
      in-differences analysis, adjusted for demographic and health characteristics, men
      had increased odds of antidepressant receipt up to 5 yr after surgery (odds ratio
      [OR] 1.49; 95% confidence interval [CI] 1.35-1.64; p<=0.0001) or radiotherapy (OR
      1.33; 95% CI 1.21-1.47; p<=0.0001). Men did not have an increased risk of
      antidepressant receipt up to 5 yr after surveillance (OR 1.15; 95% CI 0.94-1.41;
      p=0.16). Limitations include the potential for selection bias and
      misclassification due to the retrospective design of the study and the use of
      administrative databases. Thus, men with nonmetastatic PCa who initially receive
      surgery or radiotherapy, but not those who initially undergo surveillance, have
      an increased risk of antidepressant receipt after treatment. PATIENT SUMMARY: In
      this report, we examined antidepressant prescription for men after treatment of
      nonmetastatic prostate cancer across the entire population of men >=66 yr in
      Ontario, Canada, from 2002 to 2009. For men diagnosed with nonmetastatic prostate
      cancer, the risk of antidepressant receipt at 5 yr after treatment was
      significantly increased after surgery or radiotherapy, but not after
      surveillance. Providers and patients should consider the psychological effects of
      prostate cancer treatment during the survivorship period.

PMID- 30241974
TI  - Primary Surgical Treatment of Erythema Elevatum Diutinum.
AB  - Erythema elevatum diutinum (EED) is a rare skin disease caused an Arthrus-type
      immunological reaction to antigen with immune complex deposition in the cutaneous
      microvasculature, which leads to tissue damage secondary to the effects of
      complement and leukocytes. It presents as brown or red cutaneous nodules,
      papules, or plaques, often on the extensor surfaces of the hands, knees, or
      elbows. Onset usually occurs in the fourth to sixth decades but possibly younger
      in patients with human immunodeficiency virus. Medical treatment is usually
      successful; however, surgical treatment can be used when chemotherapy fails. We
      present a case of a 29-year-old man with EED treated with excision and skin
      grafting.

PMID- 30241973
TI  - Reporting and Interpreting Decision Curve Analysis: A Guide for Investigators.
AB  - CONTEXT: Urologists regularly develop clinical risk prediction models to support
      clinical decisions. In contrast to traditional performance measures, decision
      curve analysis (DCA) can assess the utility of models for decision making. DCA
      plots net benefit (NB) at a range of clinically reasonable risk thresholds.
      OBJECTIVE: To provide recommendations on interpreting and reporting DCA when
      evaluating prediction models. EVIDENCE ACQUISITION: We informally reviewed the
      urological literature to determine investigators' understanding of DCA. To
      illustrate, we use data from 3616 patients to develop risk models for high-grade
      prostate cancer (n=313, 9%) to decide who should undergo a biopsy. The baseline
      model includes prostate-specific antigen and digital rectal examination; the
      extended model adds two predictors based on transrectal ultrasound (TRUS).
      EVIDENCE SYNTHESIS: We explain risk thresholds, NB, default strategies (treat
      all, treat no one), and test tradeoff. To use DCA, first determine whether a
      model is superior to all other strategies across the range of reasonable risk
      thresholds. If so, that model appears to improve decisions irrespective of
      threshold. Second, consider if there are important extra costs to using the
      model. If so, obtain the test tradeoff to check whether the increase in NB versus
      the best other strategy is worth the additional cost. In our case study, addition
      of TRUS improved NB by 0.0114, equivalent to 1.1 more detected high-grade
      prostate cancers per 100 patients. Hence, adding TRUS would be worthwhile if we
      accept subjecting 88 patients to TRUS to find one additional high-grade prostate
      cancer or, alternatively, subjecting 10 patients to TRUS to avoid one unnecessary
      biopsy. CONCLUSIONS: The proposed guidelines can help researchers understand DCA
      and improve application and reporting. PATIENT SUMMARY: Decision curve analysis
      can identify risk models that can help us make better clinical decisions. We
      illustrate appropriate reporting and interpretation of decision curve analysis.

PMID- 30241975
TI  - Sonographic Findings Are Associated With Carpal Tunnel Symptom Severity.
AB  - PURPOSE: The purpose of this study was to identify associations between the
      clinical manifestations of carpal tunnel syndrome (CTS) and the sonographic
      measurements of the median nerve in the carpal tunnel. We hypothesized that
      sonographic changes in the median nerve from proximal to distal along the carpal
      tunnel would be associated with symptom severity scores. METHODS: We report on 38
      patients with clinical signs and symptoms of CTS in a prospective investigation.
      Subjects underwent sonographic evaluation with measurement of median nerve cross
      sectional area (CSA) at 3 locations: the level of the pronator quadratus,
      pisiform, and hamate. In addition, we measured dimensions of the carpal tunnel at
      the levels of the pisiform (inlet) and hamate (outlet). Finally, we recorded
      maximal thickness of the transverse carpal ligament (TCL). Patients underwent
      routine clinical evaluation and 31 patients had electrodiagnostic examination.
      Patients completed the Levine Katz Questionnaire (LKQ) to characterize severity
      of clinical symptoms. Each clinician was blinded to symptom severity scores.
      Pearson correlation coefficients were calculated to measure the relationship
      between LKQ score and sonographic measures. RESULTS: Median nerve CSA decreased
      over the course of the carpal tunnel from proximal to distal in 30 of 38 wrists.
      A greater absolute change in CSA of the median nerve over the course of the
      carpal tunnel between the pisiform and the hamate as well as between the pronator
      quadratus and the hamate correlated with increased severity of clinical symptoms.
      Increased thickening of the TCL also correlated with greater symptom severity
      scores. CONCLUSIONS: Changes in CSA of the median nerve as well as thickening of
      the TCL correlate with CTS severity. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic
      II.

PMID- 30241976
TI  - Common Upper Extremity Fracture Eponyms: A Look Into What They Really Mean.
AB  - Eponyms, whereas commonly used in hand surgery, are perhaps misused as often as
      they are used correctly. Many commonly used eponyms, such as Colles fracture,
      Barton fracture, Smith fracture, and Bennett fracture, were actually described
      decades before the development of radiographs. The goal of this article is to
      revisit the original descriptions of commonly used eponymous terms for distal
      radius and first metacarpal base fractures to provide clarity and enhance
      understanding of what these eponyms actually mean.

PMID- 30241977
TI  - The Effect of Radioscapholunate Fusion With and Without Distal Scaphoid and
      Triquetrum Excision on Capitolunate Contact Pressures.
AB  - PURPOSE: To determine the effects of motion-increasing modifications to
      radioscapholunate (RSL) arthrodesis on capitolunate contact pressure in cadaveric
      wrist specimens. METHODS: Ten fresh-frozen cadaveric wrists were dissected of all
      superficial soft tissue, potted in polymethyl-methacrylate, and the carpus
      exposed via a ligament-sparing capsulotomy. An RSL arthrodesis was simulated
      using 2 2.4-mm distal radius plates with locking screws. The distal scaphoid pole
      and triquetrum were removed with an osteotome and rongeur, respectively. Contact
      area, pressure, and force were measured in the capitolunate joint during the
      application of a 35-N uniaxial load using pressure-sensitive film. Measurements
      were obtained before and after simulated RSL fusion, following distal
      scaphoidectomy and after triquetrectomy. RESULTS: The combination of RSL fusion
      with distal scaphoid excision (DSE) increased contact forces in the capitolunate
      joint by 50% over controls. An RSL fusion, and RSL fusion with DSE and triquetrum
      excision (TE), exhibited intermediate levels of contact force between controls
      and RSL fusion with DSE. Capitolunate contact pressures were similar between all
      experimental groups. Contact area in the capitolunate joint increased by 43%
      after RSL fusion with DSE over intact specimen controls. Lastly, contact area in
      wrists with RSL fusion, and RSL fusion with DSE and TE, were elevated, but not
      significantly different from intact controls. CONCLUSIONS: A DSE performed at the
      time of RSL fusion results in increased midcarpal joint contact force and area,
      with resultant contact pressures unchanged. Triquetrectomy, which has been
      previously shown to improve range of motion, did not increase contact forces in
      the capitolunate joint. CLINICAL RELEVANCE: If a surgeon is contemplating
      performing an RSL arthrodesis with DSE, we recommend adding a triquetrectomy to
      improve motion because this does not add to the potentially deleterious effects
      of increased midcarpal contact force.

PMID- 30241978
TI  - Effects of noise and age on the infant brainstem response to speech.
AB  - OBJECTIVE: Background noise makes hearing speech difficult for people of all
      ages. This difficulty can be exacerbated by co-occurring developmental deficits
      that often emerge in childhood. Sentence-type speech-in-noise (SIN) tests are
      available clinically but cannot be administered to very young individuals. Our
      objective was to examine the use of an electrophysiological test of SIN, suitable
      for infants, to track developmental trajectories. METHODS: Speech-evoked
      brainstem potentials were recorded from 30 typically-developing infants in quiet
      and +10 dB SNR background noise. Infants were divided into two age groups (7-12
      and 18-24 months) and examined across development. Spectral power of the
      frequency following response (FFR) was computed using a fast Fourier Transform.
      Cross-correlations between quiet and noise responses were computed to measure
      encoding resistance to noise. RESULTS: Older infants had more robust FFR encoding
      in noise and had higher quiet-noise correlations than their younger counterparts.
      No group differences were observed in the quiet condition. CONCLUSIONS: By two
      years of age, infants show less vulnerability to the disruptive effects of
      background noise, compared to infants under 12 months. SIGNIFICANCE: Speech-in
      noise electrophysiology can be easily recorded across infancy and provides unique
      insights into developmental differences that tests conducted in quiet may miss.

PMID- 30241979
TI  - The impact of follow-up visits and diaries on patient outcome after discharge
      from intensive care: A descriptive and explorative study.
AB  - OBJECTIVES: To explore the possible effects of intensive care follow-up visits
      and diaries on patients physical and psychosocial problems at 2, 6, and 12 months
      after unit discharge as well as the patient' experiences of follow-up visits and
      diaries. METHODS: A descriptive and explorative cohort design. Patients (n = 441)
      with a length of ICU stay for >=24 hours, who responded to the 3-set 4P
      questionnaire were included. Patients were divided into groups depending on when
      they responded to the questionnaire and if had or had not a follow-up visit or a
      diary. RESULTS: Patients found the follow-up visit and the diary valuable and
      helpful during the recovery. In the univariate general linear model analyses, the
      follow-up group reported more problems in Mood and Memory. Longer length of stay
      was a predictor for unfavourable scoring in the domains Change in Appearance and
      Memory and for favourable scoring in the domain Social Life. The diary group
      reported more problems in Change in Appearance, Mood, and Memory and fewer
      problems in Social Life. CONCLUSION: No strong effects of follow-up or diary on
      patient outcomes were seen. However, because the patients experienced that the
      interventions had helped them during recovery, further exploration of the matter
      is needed in the process of testing these interventions.

PMID- 30241980
TI  - Early Outcomes After Branched and Fenestrated Endovascular Aortic Repair in
      Octogenarians.
AB  - AIM: To compare early outcome after complex endovascular aortic repair in
      octogenarians (age >= 80 years) versus non-octogenarians (age < 80 years) treated
      with fenestrated or branched stent grafts. METHODS: Single centre retrospective
      analysis from a prospectively collected database of all patients undergoing
      repair with fenestrated or branched stent grafts for para/suprarenal aortic
      aneurysm, type Ia endoleak after previous endovascular aortic repair, and thoraco
      abdominal aortic aneurysm between January 2015 and December 2017. Early all cause
      mortality, major adverse events, and need for re-intervention were analysed for
      non-octogenarians (age < 80 years) and octogenarians (age >= 80 years) at the
      time of repair. RESULTS: 207 patients (58 [28%] females) with a median age of 73
      years (IQR 68-78) underwent repair with fenestrated or branched stent grafts.
      There were 169 (81%) non-octogenarians with a median age of 72 years (IQR 65-76)
      and 38 (19%) octogenarians with a median age of 82 years (IQR 81-84). The number
      of patients with chronic kidney disease was significantly higher in the
      octogenarians (63 [37%] vs. 22 [58%], p = .03]. Nineteen patients (9%) died. The
      early mortality rate was higher in the octogenarians (12 [7%] vs. 7 [18%], p =
      .06]. Mortality rate was 4% (6/148) for elective and 22% (13/59) for urgently
      treated patients. Similar rates of post-operative sepsis, stroke, respiratory
      problems, need for dialysis, and spinal cord injury were found in both groups.
      Two patients in each group had early stent graft related re-interventions. The
      octogenarian group had increased post-operative creatinine values (1.0 [0.8-1.4]
      vs. 1.4 [1.0-1.9], p = .01). After multiple logistic regression, ASA class >=4
      and rupture were independent factors of early all cause mortality. CONCLUSIONS:
      Complex endovascular repair in octogenarians has higher early all cause mortality
      compared with non-octogenarians. Rupture and higher ASA class of >=4 are
      independent predictors for early mortality. Age >=80 years was found to be an
      independent predictor for higher early all cause mortality.

PMID- 30241981
TI  - 18F-FDG PET in the Diagnosis of Vascular Prosthetic Graft Infection: A Diagnostic
      Test Accuracy Meta-Analysis.
AB  - BACKGROUND: For the diagnosis of vascular prosthetic graft infection (VPGI), an
      intra-operative peri-graft biopsy is often required. Controversy exists regarding
      the use of imaging techniques in the diagnostic process. This study aimed to
      evaluate the diagnostic accuracy of 18-fluorine fluorodeoxyglucose (18F-FDG)
      positron emission tomography (PET) in VPGI. METHODS: A systematic search of
      electronic databases was conducted, applying a combination of free text and
      controlled vocabulary searches adapted to thesaurus headings, search operators,
      and limits to identify studies assessing the use of 18F-FDG PET in the diagnosis
      of VPGI. A meta-analysis was conducted using a mixed effects logistic regression
      bivariate model. RESULTS: Twelve studies were identified reporting a total of 433
      prostheses, of which 202 were proven to be infected. Analysis of PET scan was
      performed using five different methods: graded uptake, focal uptake, maximum
      standardised uptake value (SUVmax), tissue to background ratio (TBR), and dual
      time point (DTP). The pooled estimates for sensitivity and specificity for graded
      uptake were 0.89 (95% CI 0.73-0.96) and 0.61 (95% CI 0.48-0.74), respectively;
      they were 0.93 (95% CI 0.83-0.97) and 0.78 (95% CI 0.53-0.92) for focal uptake;
      0.98 (95% CI 0.42-0.99) and 0.80 (95% CI 0.70-0.88) for SUVmax; 0.57 (95% CI 0.39
      0.73) and 0.76 (95% CI 0.64-0.85) for TBR; and 1.00 (95% CI 0.48-1.00) and 0.88
      (95% CI 0.68-0.97) for DTP. Sensitivity analysis including studies that
      investigated the diagnostic accuracy of PET combined with computed tomography
      (CT) showed higher sensitivity and specificity for focal uptake, graded uptake,
      and SUVmax than 18F-FDG PET alone. CONCLUSIONS: This meta-analysis suggests that
      18F-FDG PET has a high sensitivity in diagnosing VPGI and its accuracy can be
      further increased by combining PET with CT.

PMID- 30241982
TI  - Correlation Between Computed Tomography Features and Clinical Presentation and
      Management of Isolated Superior Mesenteric Artery Dissection.
AB  - OBJECTIVES: To examine the correlation between computed tomography (CT) features
      and clinical presentation and to assess the management strategy for patients with
      isolated superior mesenteric artery (SMA) dissection. MATERIAL AND METHODS:
      Retrospective analysis of clinical records and CT findings of patients with
      isolated superior mesenteric artery dissection treated between 2012 and 2016. The
      relationship between CT features and clinical symptoms and treatment options was
      studied. Follow up CT images were reviewed and telephone interviews were
      conducted with patients. RESULTS: Sixty-nine patients with isolated SMA
      dissection (47 symptomatic and 22 asymptomatic) were evaluated. The dissection
      length in patients with Sakamoto type IV lesions was significantly longer than
      that in patients with other lesion types (83.0 +/- 40.1 mm, p = .001). Compared
      with the asymptomatic group, the symptomatic group had longer dissections (63.5
      +/- 35.9 mm, p < .001) and lesser true lumen diameter (3.1 +/- 1.7 mm, p = .044).
      Fifty-six patients were treated conservatively, of whom 31 showed clinical
      improvement and exhibited no morphological change during long-term follow up.
      CONCLUSIONS: In patients with isolated SMA dissection, clinical symptoms were
      related to the length of dissection and degree of true lumen stenosis.
      Conservative treatment was commonly employed and yielded favourable outcomes.

PMID- 30241983
TI  - The kinematics of 1-on-1 rugby tackling: a study using 3-dimensional motion
      analysis.
AB  - BACKGROUND: Although past studies using video analysis indicated that the arm
      tackle and head-in-front shoulder tackle are possible risks for shoulder
      dislocation, the underlying mechanisms of tackling-related shoulder dislocation
      have not been sufficiently investigated. This study aimed to analyze the
      kinematic aspects of these tackling motions in 1-on-1 tackles in an experimental
      setting using a 3-dimensional motion-capture system. METHODS: A total of 65 one
      on-one tackles were recorded using a marker-based, automatic, digitizing motion
      capture system. A documented tackle was classified into 1 of 3 types, which was
      decided based on the first point of contact on the ball carrier and the head
      position at the time of impact: shoulder tackle (reference tackle), arm tackle,
      and head-in-front tackle. The orientations of the head, trunk, and shoulder at
      impact were calculated and statistically compared with each other. RESULTS: The
      distribution of tackles recorded in this study was as follows: 38 shoulder, 23
      arm, and 4 head-in-front tackles. In comparison with the shoulder tackle as a
      reference, shoulder abduction on the side of impact was higher in both the arm
      and head-in-front tackles, while shoulder external rotation was lower in the head
      in-front tackles. In the latter type of tackle, significant decreases in neck
      extension and ipsilateral neck rotation were also indicated. CONCLUSION: The
      kinematics in both the arm tackle and the head-in-front tackle is significantly
      different from that in the shoulder tackle and may represent a distinct risk
      factor for shoulder dislocation.

PMID- 30241984
TI  - Grammont Award 2018: Scapular fractures in reverse shoulder arthroplasty
      (Grammont style): prevalence, functional, and radiographic results with minimum 5
      year follow-up.
AB  - BACKGROUND: Scapular fractures after reverse shoulder arthroplasty (RSA) are an
      increasingly reported complication. Information is missing regarding midterm to
      long-term follow-up consequences. The aim of this study was to determine the rate
      of scapular fracture (acromial base and spine) after Grammont-style RSA and to
      report functional and radiographic results of patients with a minimum 5-year
      follow-up. MATERIALS AND METHODS: We retrospectively reviewed 1953 Grammont-style
      RSAs in 1745 patients in a multicenter study. Of these, 953 patients (1035 RSAs)
      had minimum 5-year follow-up for functional and radiographic assessment
      (anteroposterior and scapular Y views. RESULTS: Twenty-six patients (1.3%) had
      sustained a scapular fracture; of these, 19 (10 acromial base and 9 spine
      fractures) had minimum 5-year follow-up and were reviewed at a mean follow-up of
      97 months. Three patients (15.8%) were diagnosed at the last follow-up after an
      undiagnosed fracture. There were 3 traumatic cases (15.8%) and 13 (68.4%) without
      antecedent trauma. These 16 patients underwent nonoperative treatment. The
      fracture was healed in 8 (4 acromion and 4 spine). The average active forward
      elevation was 109 degrees  (range, 50 degrees -170 degrees ), and the Constant
      score was 47.0 points (range, 8-81 points). CONCLUSIONS: Scapular fractures after
      Grammont-style RSAs are rare (1.3%) but remain a concern. These fractures occur
      mainly in the early postoperative 6 months. Immobilization with an abduction
      splint frequently resulted in nonunion or malunion. Final functional outcomes are
      poor regardless of acromial or spine fracture compared with primary RSA without
      fracture.

PMID- 30241985
TI  - What I've learned.

PMID- 30241986
TI  - The effect of an orthopedic specialty hospital on operating room efficiency in
      shoulder arthroplasty.
AB  - BACKGROUND: Operating room (OR) time is a major cost to the health care system.
      Therefore, increasing OR efficiency to save time may be a cost-saving tool. This
      study analyzed OR efficiency in shoulder arthroplasty at an orthopedic specialty
      hospital (OSH) and a tertiary referral center (TRC). METHODS: All primary
      shoulder arthroplasties performed at our OSH and TRC were identified (2013-2015).
      Manually matched cohorts from the OSH and TRC were compared for OR times. Three
      times (minutes) were recorded: anesthesia preparation time (APT; patient in room
      to skin incision), surgical time (ST; skin incision to skin closed), conclusion
      time (CT; skin closed to patient out of room). RESULTS: There were 136 primary
      shoulder arthroplasties performed at the OSH and matched with 136 at the TRC. OSH
      and TRC patients were similar in age (P = .95), body mass index (P = .97),
      Charlson Comorbidity Index (P = 1.000), sex (P = 1.000), procedure (P = 1.000),
      insurance status (P = .714), discharge destination (P = .287), and diagnoses (P =
      .354). These matched populations had similar ST (OSH: 110.0 +/- 26.6 minutes,
      TRC: 113.4 +/- 28.7 minutes; P = .307). APT (39.2 +/- 8.0 minutes) and CT (7.6 +/
      3.8 minutes) were shorter in the OSH patients than APT (46.3 +/- 8.8 minutes; P
      < .001) and CT (11.2 +/- 4.7 minutes; P < .001) in TRC patients. Total
      nonoperative time (sum of APT and CT) at the OSH (46.8 +/- 8.9 minutes) was
      shorter than at the TRC (57.5 +/- 10.4 minutes; P < .001). CONCLUSIONS: Despite
      similar patient populations and case complexity, the OR efficiency at an OSH was
      superior to a TRC. Further analysis is needed to determine the financial
      implications of this superior OR efficiency.

PMID- 30241987
TI  - Exploring Antipsychotic Prescribing Behaviors for Nursing Home Residents With
      Dementia: A Qualitative Study.
AB  - OBJECTIVES: Caution is advised when prescribing antipsychotics to people with
      dementia. This study explored the determinants of appropriate, evidence-based
      antipsychotic prescribing behaviors for nursing home residents with dementia,
      with a view to informing future quality improvement efforts and behavior change
      interventions. DESIGN: Semistructured qualitative interviews based on the
      Theoretical Domains Framework (TDF). SETTING AND PARTICIPANTS: A purposive sample
      of 27 participants from 4 nursing homes, involved in the care of nursing home
      residents with dementia (8 nurses, 5 general practitioners, 5 healthcare
      assistants, 3 family members, 2 pharmacists, 2 consultant geriatricians, and 2
      consultant psychiatrists of old age) in a Southern region of Ireland. MEASURES:
      Using framework analysis, the predominant TDF domains and determinants
      influencing these behaviors were identified, and explanatory themes developed.
      RESULTS: Nine predominant TDF domains were identified as influencing appropriate
      antipsychotic prescribing behaviors. Participants' effort to achieve "a fine
      balance" between the risks and benefits of antipsychotics was identified as the
      cross-cutting theme that underpinned many of the behavioral determinants. On one
      hand, neither healthcare workers nor family members wanted to see residents over
      sedated and without a quality of life. Conversely, the reality of needing to
      protect staff, family members, and residents from potentially dangerous
      behavioral symptoms, in a resource-poor environment, was emphasized. The
      implementation of best-practice guidelines was illustrated through 3 explanatory
      themes ("human suffering"; "the interface between resident and nursing home"; and
      "power and knowledge: complex stakeholder dynamics"), which conceptualize how
      different nursing homes strike this "fine balance." CONCLUSIONS: Implementing
      evidence-based antipsychotic prescribing practices for nursing home residents
      with dementia remains a significant challenge. Greater policy and institutional
      support is required to help stakeholders strike that "fine balance" and
      ultimately make better prescribing decisions. This study has generated a deeper
      understanding of this complex issue and will inform the development of an
      evidence-based intervention.

PMID- 30241988
TI  - Microbiological features, clinical characteristics and outcomes of infective
      endocarditis in adults with and without hemodialysis: A 10-year retrospective
      study in Northern Taiwan.
AB  - BACKGROUND/PURPOSES: Infective endocarditis (IE) is an important cause of
      morbidity and mortality in hemodialysis (HD) patients. Data on the differences in
      the microbiological features as well as clinical characteristics and outcomes of
      HD and non-HD patients with IE are limited. METHODS: Medical records of patients
      (aged over 20 years) with IE were retrospectively reviewed from January 2008 to
      June 2017 in a tertiary care center in Northern Taiwan. Those with definite or
      possible IE were included in the study. The clinical characteristics,
      microbiological results, echocardiographic findings and outcomes of patients were
      analyzed. RESULTS: Of the 183 patients with definite or possible IE, 47 had
      undergone HD and 136 had not. Advanced age (67.3 vs. 61.5 years, p = 0.027), more
      female gender (51.1% vs. 33.8%, p = 0.036), comorbidities (a high Charlson
      comorbidity index, 8.17 vs. 4.21, p < 0.001), diabetes mellitus (68.1% vs. 35.3%,
      p < 0.001), and hypertension (85.1% vs. 53.7%, p < 0.001) were commonly observed
      in HD patients than in non-HD patients. The yield rate of the blood cultures was
      higher in HD group than in non-HD group (89.4% vs. 72.8%, p = 0.02). The
      proportion of methicillin-resistant Staphylococcus aureus was significantly
      higher in HD group than in non-HD group (31.9% vs. 5.9%, p < 0.001). HD patients
      versus non-HD patients had higher cardiac complication rates (38.3% vs. 14%, p <
      0.001). CONCLUSION: Advanced age, sex (female), comorbidities, diabetes mellitus,
      and hypertension were more common in HD patients than in non-HD patients with IE.
      HD patients had higher proportion of methicillin-resistant S. aureus and cardiac
      complication rates than non-HD patients with IE. Culture-negative IE was more
      common in non-HD patients.

PMID- 30241989
TI  - A qualitative study of patient experience when switching from paliperidone
      palmitate once monthly (PP1M) to paliperidone palmitate three monthly (PP3M) long
      acting injectable antipsychotic.

PMID- 30241990
TI  - A potential role for adjunctive omega-3 polyunsaturated fatty acids for
      depression and anxiety symptoms in recent onset psychosis: Results from a 16 week
      randomized placebo-controlled trial for participants concurrently treated with
      risperidone.
AB  - : Omega-3 treatment studies for multi-episode schizophrenia or clinical high risk
      for conversion to psychosis states have had variable, and often negative,
      results. To examine adjunctive omega-3 treatment for recent onset psychosis,
      participants aged 15-40 years with recent onset schizophrenia-spectrum (n = 46)
      or bipolar (n = 4) disorders and current psychotic symptoms were treated for 16
      weeks with risperidone and randomly-assigned omega-3 (EPA 740 mg and DHA 400 mg
      daily) or matching placebo. The primary outcome measure was the Brief Psychiatric
      Rating Scale (BPRS) total score. Mean lifetime antipsychotic exposure was 18.1
      days. Length of time in treatment, risperidone dose and number of omega-3/placebo
      capsules taken did not differ between conditions. Longitudinal analysis of the
      total BPRS score revealed a trend level (p = 0.0826) treatment effect favoring
      omega-3 treatment. Lorazepam was an allowed concomitant medication. Among the
      subgroup (N = 23) who did not receive lorazepam, the treatment effect on BPRS
      total scores favoring omega-3 was significant (p = 0.0406) and factor scores
      analyses revealed a substantial decrease in depression-anxiety with omega-3 but
      no change with placebo (treatment-by-time interaction, p = 0.0184). Motor side
      effects did not differ between conditions. Analysis of Systematic Assessment for
      Treatment Emergent Events assessments revealed fewer adverse events overall with
      omega-3 compared with placebo with the largest differences between conditions
      (all favoring omega-3) on confusion, anxiety, depression, irritability, and
      tiredness/fatigue. These results suggest that omega-3 adjuvant treatment is a
      potential option for depression and anxiety symptoms of people with recent onset
      psychosis. Further research is needed to confirm this potential. CLINICAL TRIAL
      REGISTRATION: NCT01786239.

PMID- 30241991
TI  - Efficacy and Toxicity of Idarubicin Versus High-dose Daunorubicin for Induction
      Chemotherapy in Adult Acute Myeloid Leukemia: A Systematic Review and Meta
      analysis.
AB  - BACKGROUND: The 2 main formulations of anthracycline used for acute myeloid
      leukemia (AML) induction therapy are idarubicin (IDA) and daunorubicin. PATIENTS
      AND METHODS: The present systematic review and meta-analysis compared the
      efficacy and toxicity between IDA and high-dose daunorubicin (HDD) for induction
      therapy for adult AML. Relevant studies reported before June 2018 were searched
      from the Medline and Embase databases. RESULTS: A total of 5 studies with 1809
      participants (3 randomized controlled studies and 2 retrospective cohort studies)
      met the eligibility criteria and were included in the meta-analysis. The patients
      in the IDA arm for induction therapy had a significantly greater complete
      response rate after the first course of induction therapy compared with those in
      the HDD arm (66.7% vs. 61.1%, respectively; odds ratio, 1.23; P = .04; I2 = 0%).
      A significantly lower rate of refractory AML was also observed in the IDA group
      than in the HDD group (16.8% vs. 20.7%, respectively; odds ratio, 0.77; P = .04;
      I2 = 0%). However, no difference was found in the long-term overall survival
      between the 2 groups. Also, the induction mortality rate, febrile neutropenia
      rate, and cardiotoxicity rate were not significantly different between the 2
      groups. The major limitation was the relatively small number of included studies,
      which could have limited the power of the meta-analysis to demonstrate
      significant long-term benefits. CONCLUSION: The complete response rate after the
      first course of induction therapy was significantly greater among adult patients
      with AML who had received IDA as part of induction therapy compared with those
      who had received HDD.

PMID- 30241992
TI  - The Preferred Attributes of a Trauma Team Leader: Evidence From a Discrete Choice
      Experiment.
AB  - OBJECTIVE: Leaders of a pediatric trauma team are tasked with managing rapidly
      changing diagnostic and treatment challenges, while ensuring the entire team
      functions effectively to produce optimal patient outcomes. An effective trauma
      team leader is often thought to be self-evident, and there is little formal
      literature identifying the leadership characteristics and attributes associated
      with optimal trauma team performance. The purpose of this study was to elicit the
      trauma team leader traits and characteristics deemed of greatest utility by
      members of the pediatric trauma team. DESIGN, SETTING, PARTICIPANTS: Members of
      the pediatric trauma team at British Columbia Children's Hospital were asked to
      participate in a semistructured interview to identify trauma team leader
      attributes associated with maximal team performance. Using the attributes, we
      constructed a discrete choice experiment (DCE). DCEs, developed in the economics
      and market research setting, allow participants to express preferences among
      finite alternatives, with subsequent statistical analysis that allows
      quantitative comparison of the utility of selected attributes. RESULTS: After
      interviewing 21 trauma team practitioners, 6 themes were identified as being most
      important for trauma team leadership. The developed DCE was administered to 64
      members of the trauma team. Analysis of the DCE revealed the most important
      attributes were collaboration, strong communication, and decisiveness. The
      attribute of least utility was experience. The specific leadership qualities that
      provided the most utility to the trauma team included "actively involves input
      for team" (mean utility [MU]: 0.70; standard error [SE]: 0.11) and "concise
      communication, at times closed-loop" (MU: 0.52; SE: 0.09). "Hesitant and unclear
      communication" (MU: -0.88; SE: 0.09) and "often indecisive" (MU: -0.68; SE: 0.10)
      were deemed most detrimental (negative utility) to the team's function.
      CONCLUSIONS: This study is novel in applying a strategy to identify and quantify
      the relative value of trauma team leader attributes. When designing education
      initiatives for pediatric trauma care teams, defining trauma team quality
      metrics, and providing continuing medical education for the team leader, it is
      essential to incorporate preferred leadership characteristics. Crisis resource
      management skills benefit greatly from an understanding of the preferred
      attributes, as defined and evaluated by other trauma team members.

PMID- 30241993
TI  - Efficacy and cost-effectiveness of therapist-guided internet cognitive
      behavioural therapy for paediatric anxiety disorders: a single-centre, single
      blind, randomised controlled trial.
AB  - BACKGROUND: Paediatric anxiety disorders are associated with substantial
      disability and long-term adverse consequences, but only a small proportion of
      affected children have access to evidence-based treatment. Internet-delivered
      cognitive behavioural therapy (ICBT) could help increase accessibility but needs
      further rigorous assessment. We aimed to assess the efficacy and cost
      effectiveness of ICBT in the treatment of paediatric anxiety disorders. METHODS:
      We did a single-blind randomised controlled trial in a clinical research unit
      within the Child and Adolescent Mental Health Services in Stockholm (Sweden).
      Eligible participants were children aged 8-12 years with a diagnosis of a
      principal anxiety disorder (seperation anxiety disorder, generalised anxiety
      disorder, specific phobia, social anxiety disorder, or panic disorder) of at
      least moderate severity. We randomly allocated participants (1:1) to ICBT or
      internet-delivered child-directed play, an active comparator aimed to improve
      parent-child relationships and increase a child's self-esteem without directly
      targeting anxiety. Block sizes for the randomisation varied between four and six
      and were generated using a computer random-number generator, and the allocation
      was concealed from the researchers by opaque sealed envelopes. Both treatment
      programmes comprised 12 modules presented over 12 weeks with weekly asynchronous
      online therapist support, and consisted of texts, films, illustrations, and
      exercises. The primary outcome was severity rating of the principal anxiety
      disorder 12-weeks post-treatment, via the Anxiety Disorder Interview Schedule for
      Diagnostic and Statistical Manual of Mental Disorders-IV (a rating of at least 4
      corresponds to meeting the criteria for the principal diagnosis), assessed by
      clinicians masked to treatment allocation. All participants were included in the
      primary analysis (intention-to-treat). This trial is registered at
      ClinicalTrials.gov, number NCT02350257. FINDINGS: Between March 11, 2015, and Oct
      21, 2016, 131 participants were recruited and allocated to either ICBT (n=66) or
      internet-delivered child-directed play (n=65). The clinician-assessed severity
      rating of the principal anxiety disorder improved significantly after the 12
      weeks treatment period for participants in both ICBT (within-group effect size
      1.22, 95% CI 0.78-1.65) and the active control (0.72, 0.44-1.00) groups. However,
      greater improvement was seen with ICBT than with the active control (estimated
      mean difference 0.79, 95% CI 0.42-1.16, p=0.002; between-group effect size 0.77,
      95% CI 0.40-1.15). 29 (48%) participants in the ICBT group no longer had their
      principal diagnosis, compared to nine (15%) in the active control group (odds
      ratio 5.41, 95% CI 2.26 to 12.90, p<0.0001); the number needed to treat for ICBT
      to gain one additional participant in remission was three (95% CI 2.85 to 3.15).
      ICBT resulted in an average societal-cost saving of ?493.05 (95% CI 477.17 to
      508.92) per participant. No severe adverse events were reported. INTERPRETATION:
      ICBT is an efficacious and cost-effective treatment for paediatric anxiety
      disorders that should be considered for implementation in routine clinical care.
      FUNDING: The Swedish Research Council for Health, Working Life and Welfare, and
      Stockholm County Council.

PMID- 30241994
TI  - Nurturing care for children with developmental disabilities: a moral imperative
      for sub-Saharan Africa.

PMID- 30241995
TI  - Treatment of paediatric anxiety disorders: what next?

PMID- 30241996
TI  - Influence of sleep on developing brain functions and structures in children and
      adolescents: A systematic review.
AB  - This systematic review examined the associations between sleep and brain
      functions and structures in children and adolescents aged 1-17 ys. Included
      studies (n = 24) were peer-reviewed and met the a priori determined population
      (apparently healthy children and adolescents aged 1 y to 17 ys),
      intervention/exposure/comparator (various sleep characteristics including
      duration, architecture, quality, timing), and outcome criteria (brain functions
      and/or brain structures, excluding cognitive function outcomes). Collectively,
      the reviewed studies report some relationships between inadequate sleep and
      resultant differences in brain functions or structures. Although the research
      presented supports and offers more insight into the importance of sleep for the
      developing brain of children and adolescents, no firm conclusions that apply
      broadly may be drawn from these results, particularly because of the diversity of
      the sleep variables and outcomes. However, it is clear that sleeping habits in
      the pediatric population should be prioritized. Health care providers should
      continue to recommend healthy sleep practices and adequate time for sleep, as
      they are essential for overall health, including brain health.

PMID- 30241997
TI  - Low-grade inflammation in the relationship between sleep disruption,
      dysfunctional adiposity, and cognitive decline in aging.
AB  - Aging is characterized by a progressive increase in proinflammatory status. This
      state, known as inflammaging, has been associated with cognitive decline in
      normal and pathological aging. However, this relationship has been inconsistently
      reported, likely because it is conditioned by other factors also affected by the
      aging process. Sleep and adiposity are two factors in particular that show
      significant alterations with aging and have been related to both cognitive
      decline and inflammaging. Given the consequences this state also has for brain
      integrity and cognition, we discuss here evidence supporting the potential
      mediating role of chronic low-grade systemic inflammation in the complex
      relationship between impaired sleep, dysfunctional adiposity, and cognitive
      decline through the common pathway of neuroinflammation. This review proposes a
      multi-factor model of aging-related cognitive decline that highlights the
      reciprocal interactions between sleep, the circadian system, and inflammation on
      the one hand, and between sleep, adiposity, and hormone resistance on the other.
      The model identifies sleep and adiposity as modifiable lifestyle factors that can
      be targeted to maximize cognitive function and quality of life in the elderly.

PMID- 30241998
TI  - Biomarkers of dementia in obstructive sleep apnea.
AB  - Epidemiologic and mechanistic evidence is increasingly supporting the notion that
      obstructive sleep apnea is a risk factor for dementia. Hence, the identification
      of patients at risk of cognitive decline due to obstructive sleep apnea may
      significantly improve preventive strategies and treatment decision-making.
      Cerebrospinal fluid and blood biomarkers obtained through genomic, proteomic and
      metabolomic approaches are improving the ability to predict incident dementia.
      Therefore, fluid biomarkers have the potential to predict vulnerability to
      neurodegeneration in individuals with obstructive sleep apnea, as well as deepen
      our understanding of pathophysiological processes linking obstructive sleep apnea
      and dementia. Many fluid biomarkers linked to Alzheimer's disease and vascular
      dementia show abnormal levels in individuals with obstructive sleep apnea,
      suggesting that these conditions share common underlying mechanisms, including
      amyloid and tau protein neuropathology, inflammation, oxidative stress, and
      metabolic disturbances. Markers of these processes include amyloid-beta, tau
      proteins, inflammatory cytokines, acute-phase proteins, antioxydants and oxidized
      products, homocysteine and clusterin (apolipoprotein J). Thus, these biomarkers
      may have the ability to identify adults with obstructive sleep apnea at high risk
      of dementia and provide an opportunity for therapeutic intervention. Large cohort
      studies are necessary to establish a specific fluid biomarker panel linking
      obstructive sleep apnea to dementia risk.

PMID- 30241999
TI  - Outcome of bariatric surgery in older patients.
AB  - BACKGROUND: People are living longer than they were expected to 2 decades ago.
      Increased life expectancy and reduced mortality encompasses a simultaneous
      increase in the number of older adults with obesity that entails an increase of
      co-morbidities, such as diabetes, hypertension, cancer, and many other diseases.
      The aim of our study was to compare the outcomes of bariatric surgery in patients
      age >=65 in comparison with younger patients. METHODS: This retrospective study
      compares bariatric surgeries performed in a private institution between the years
      2013 and 2015. The study included 9044 patients divided into an older group (451
      patients) and the younger group (8593 patients). RESULTS: In the younger group,
      bariatric surgery is distributed as follows: 77.68% sleeve gastrectomy, 12.72%
      gastric banding, 9.27% gastric bypass, and .33% duodenal switch or
      biliopancreatic diversion; in the older group: 70.51% sleeve gastrectomy, 15.08%
      gastric bypass, 13.97% gastric band, and .44% biliopancreatic diversion. In the
      control group 550 cases (6.4%) underwent revisional surgery; 64 cases (14.10%)
      underwent revision in the older group. Older patients lost less excess weight
      than younger patients (72.44% versus 86.11%, respectively). Older patients
      presented higher rates of complications (8.42% versus 5.59%), co-morbidities
      (77.60% versus 55.45%), and revisions (1.33% versus .77%). There was no
      statistical difference in hospital stay between older group and control group
      (2.27 versus 2.23, respectively). When performing a Clavien-Dindo classification,
      we demonstrated significant differences in class 3B and 4A and no differences in
      other classes. Two deaths occurred in the control group. Diabetes, fatty liver,
      and sleep apnea have been improved or remitted in >90% of patients in both
      groups, hypertension and hyperlipidemia by >80%, and hyperuricemia and ischemic
      heart disease were improved or resolved in >70% of the patients CONCLUSIONS:
      Bariatric surgery in the elderly has more complications, but it can still be
      considered safe.

PMID- 30242000
TI  - ASMBS Position Statement on medium- and long-term durability of weight loss and
      diabetic outcomes after conventional stapled bariatric procedures.

PMID- 30242002
TI  - Burnt out GPs: five minutes with . . . Clare Gerada.

PMID- 30242001
TI  - Correction to Lancet Glob Health 2018; published online Sept 5.
      https://doi.org/10.1016/S2214-109X(18)30386-3.

PMID- 30242003
TI  - A Cotransformation Method To Identify a Restriction-Modification Enzyme That
      Reduces Conjugation Efficiency in Campylobacter jejuni.
AB  - Conjugation is an important mechanism for horizontal gene transfer in
      Campylobacter jejuni, the leading cause of human bacterial gastroenteritis in
      developed countries. However, to date, the factors that significantly influence
      conjugation efficiency in Campylobacter spp. are still largely unknown. Given
      that multiple recombinant loci could independently occur within one recipient
      cell during natural transformation, the genetic materials from a high-frequency
      conjugation (HFC) C. jejuni strain may be cotransformed with a selection marker
      into a low-frequency conjugation (LFC) recipient strain, creating new HFC
      transformants suitable for the identification of conjugation factors using a
      comparative genomics approach. To test this, an erythromycin resistance selection
      marker was created in an HFC C. jejuni strain; subsequently, the DNA of this
      strain was naturally transformed into NCTC 11168, an LFC C. jejuni strain,
      leading to the isolation of NCTC 11168-derived HFC transformants. Whole-genome
      sequencing analysis and subsequent site-directed mutagenesis identified Cj1051c,
      a putative restriction-modification enzyme (aka CjeI) that could drastically
      reduce the conjugation efficiency of NCTC 11168 (>5,000-fold). Chromosomal
      complementation of three diverse HFC C. jejuni strains with CjeI also led to a
      dramatic reduction in conjugation efficiency (~1,000-fold). The purified
      recombinant CjeI could effectively digest the Escherichia coli-derived shuttle
      vector pRY107. The endonuclease activity of CjeI was abolished upon short heat
      shock treatment at 50 degrees C, which is consistent with our previous
      observation that heat shock enhanced conjugation efficiency in C. jejuni
      Together, in this study, we successfully developed and utilized a unique
      cotransformation strategy to identify a restriction-modification enzyme that
      significantly influences conjugation efficiency in C. jejuni IMPORTANCE
      Conjugation is an important horizontal gene transfer mechanism contributing to
      the evolution of bacterial pathogenesis and antimicrobial resistance.
      Campylobacter jejuni, the leading foodborne bacterial organism, displays
      significant strain diversity due to horizontal gene transfer; however, the
      molecular components influencing conjugation efficiency in C. jejuni are still
      largely unknown. In this study, we developed a cotransformation strategy for
      comparative genomics analysis and successfully identified a restriction
      modification enzyme that significantly influences conjugation efficiency in C.
      jejuni The new cotransformation strategy developed in this study is also expected
      to be broadly applied in other naturally competent bacteria for functional
      comparative genomics research.

PMID- 30242004
TI  - DIETARY FATTY ACIDS SUSTAIN GROWTH OF HUMAN GUT MICROBIOTA.
AB  - While a substantial amount of dietary fats escape absorption in the human small
      intestine and reach the colon, the ability of resident microbiota to utilize
      these dietary fats for growth has not been investigated in detail. In this study
      we used an in vitro multi-vessel simulator system of the human colon to reveal
      that human gut microbiota is able to utilize typically consumed dietary fatty
      acids to sustain growth. Gut microbiota adapted quickly to a macronutrient switch
      from a balanced Western diet type medium to its variant lacking carbohydrates and
      proteins. We defined specific genera that increased their abundance on the fats
      only medium, including Alistipes, Bilophila, and several genera of class
      Gammaproteobacteria. In contrast, abundances of well-known glycan and protein
      degraders including Bacteroides, Clostridium, and Roseburia were reduced in such
      conditions. Predicted prevalences of microbial genes coding for fatty acid
      degradation enzymes and anaerobic respiratory reductases were significantly
      increased in the fats-only environment, whereas the abundance of glycan
      degradation genes was diminished. These changes also resulted in lower microbial
      production of short chain fatty acids and antioxidants. Our findings provide
      justification for the previously observed alterations in gut microbiota observed
      in human and animal studies of high-fat diets.Importance Increased intake of fats
      in many developed countries raised awareness of potentially harmful and
      beneficial effects of high fat consumption on human health. Some dietary fats
      escape digestion in the small intestine and reach the colon where they can be
      metabolized by gut microbiota. We show that human gut microbes are able to
      maintain a complex community when supplied with dietary fatty acids as the only
      nutrient and carbon sources. Such fatty acid based growth leads to lower
      production of short chain fatty acids and antioxidants by community members,
      which might potentially have negative health consequences on the host.

PMID- 30242005
TI  - Methanogens and Iron-Reducing Bacteria: the Overlooked Members of Mercury
      Methylating Microbial Communities in Boreal Lakes.
AB  - Methylmercury is a potent human neurotoxin which biomagnifies in aquatic food
      webs. Although anaerobic microorganisms containing the hgcA gene potentially
      mediate the formation of methylmercury in natural environments, the diversity of
      these mercury-methylating microbial communities remains largely unexplored.
      Previous studies have implicated sulfate-reducing bacteria as the main mercury
      methylators in aquatic ecosystems. In the present study, we characterized the
      diversity of mercury-methylating microbial communities of boreal lake sediments
      using high-throughput sequencing of 16S rRNA and hgcA genes. Our results show
      that in the lake sediments, Methanomicrobiales and Geobacteraceae also represent
      abundant members of the mercury-methylating communities. In fact, incubation
      experiments with a mercury isotopic tracer and molybdate revealed that only
      between 38% and 45% of mercury methylation was attributed to sulfate reduction.
      These results suggest that methanogens and iron-reducing bacteria may contribute
      to more than half of the mercury methylation in boreal lakes.IMPORTANCE Despite
      the global awareness that mercury, and methylmercury in particular, is a
      neurotoxin to which millions of people continue to be exposed, there are sizable
      gaps in the understanding of the processes and organisms involved in
      methylmercury formation in aquatic ecosystems. In the present study, we shed
      light on the diversity of the microorganisms responsible for methylmercury
      formation in boreal lake sediments. All the microorganisms identified are
      associated with the processing of organic matter in aquatic systems. Moreover,
      our results show that the well-known mercury-methylating sulfate-reducing
      bacteria constituted only a minor portion of the potential mercury methylators.
      In contrast, methanogens and iron-reducing bacteria were important contributors
      to methylmercury formation, highlighting their role in mercury cycling in the
      environment.

PMID- 30242006
TI  - Functional Redundancy in the Hydroxycinnamate Catabolism Pathways of the Salt
      Marsh Bacterium Sagittula stellata E-37.
AB  - The hydroxycinnamates (HCAs) ferulate and p-coumarate are among the most abundant
      constituents of lignin, and their degradation by bacteria is an essential step in
      the remineralization of vascular plant material. Here, we investigate the
      catabolism of these two HCAs by the marine bacterium Sagittula stellata E-37, a
      member of the roseobacter lineage with lignolytic potential. Bacterial
      degradation of HCAs is often initiated by the activity of a hydroxycinnamoyl
      coenzyme A (hydroxycinnamoyl-CoA) synthase. Genome analysis of S. stellata
      revealed the presence of two feruloyl-CoA (fcs) synthase homologs, an unusual
      occurrence among characterized HCA degraders. In order to elucidate the role of
      these homologs in HCA catabolism, fcs-1 and fcs-2 were disrupted using
      insertional mutagenesis, yielding both single and double fcs mutants. Growth on p
      coumarate was abolished in the fcs double mutant, whereas maximum cell yield on
      ferulate was only 2% of that of the wild type. Interestingly, the single mutants
      demonstrated opposing phenotypes, where the fcs-1 mutant showed impaired growth
      (extended lag and ~60% of wild-type rate) on p-coumarate, and the fcs-2 mutant
      showed impaired growth (extended lag and ~20% of wild-type rate) on ferulate,
      pointing to distinct but overlapping roles of the encoded fcs homologs, with fcs
      1 primarily dedicated to p-coumarate utilization and fcs-2 playing a dominant
      role in ferulate utilization. Finally, a tripartite ATP-independent periplasmic
      (TRAP) family transporter was found to be required for growth on both HCAs. These
      findings provide evidence for functional redundancy in the degradation of HCAs in
      S. stellata E-37 and offer important insight into the genetic complexity of
      aromatic compound degradation in bacteria.IMPORTANCE Hydroxycinnamates (HCAs) are
      essential components of lignin and are involved in various plant functions,
      including defense. In nature, microbial degradation of HCAs is influential to
      global carbon cycling. HCA degradation pathways are also of industrial relevance,
      as microbial transformation of the HCA, ferulate, can generate vanillin, a
      valuable flavoring compound. Yet, surprisingly little is known of the genetics
      underlying bacterial HCA degradation. Here, we make comparisons to previously
      characterized bacterial HCA degraders and use a genetic approach to characterize
      genes involved in catabolism and uptake of HCAs in the environmentally relevant
      marine bacterium Sagittula stellata We provide evidence of overlapping substrate
      specificity between HCA degradation pathways and uptake proteins. We conclude
      that S. stellata is uniquely poised to utilize HCAs found in the complex mixtures
      of plant-derived compounds in nature. This strategy may be common among marine
      bacteria residing in lignin-rich coastal waters and has potential relevance to
      biotechnology sectors.

PMID- 30242007
TI  - Toxicity of Potential Fungal Defense Proteins towards the Fungivorous Nematodes
      Aphelenchus avenae and Bursaphelenchus okinawaensis.
AB  - Resistance of fungi to predation is thought to be mediated by toxic metabolites
      and proteins. Many of these fungal defense effectors are highly abundant in the
      fruiting body and not produced in the vegetative mycelium. The defense function
      of fruiting body-specific proteins, however, including cytoplasmically localized
      lectins and antinutritional proteins such as biotin-binding proteins, is mainly
      based on toxicity assays using bacteria as a heterologous expression system, with
      bacterivorous/omnivorous model organisms as predators. Here, we present an
      ecologically more relevant experimental setup to assess the toxicity of potential
      fungal defense proteins towards the fungivorous, stylet-feeding nematodes
      Aphelenchus avenae and Bursaphelenchus okinawaensis As a heterologous expression
      host, we exploited the filamentous fungus Ashbya gossypii Using this new system,
      we assessed the toxicity of six previously characterized, cytoplasmically
      localized, potential defense proteins from fruiting bodies of different fungal
      phyla against the two fungivorous nematodes. We found that all of the tested
      proteins were toxic against both nematodes, albeit to various degrees. The
      toxicity of these proteins against both fungivorous and bacterivorous nematodes
      suggests that their targets have been conserved between the different feeding
      groups of nematodes and that bacterivorous nematodes are valid model organisms to
      assess the nematotoxicity of potential fungal defense proteins.IMPORTANCE Our
      results support the hypothesis that cytoplasmic proteins abundant in fungal
      fruiting bodies are involved in fungal resistance against predation. The toxicity
      of these proteins toward stylet-feeding nematodes, which are also capable of
      feeding on plants, and the abundance of these proteins in edible mushrooms, may
      open possible avenues for biological crop protection against parasitic nematodes,
      e.g., by expression of these proteins in crops.

PMID- 30242008
TI  - Alanine, a Novel Growth Substrate for the Acetogenic Bacterium Acetobacterium
      woodii.
AB  - Acetogenic bacteria are an ecophysiologically important group of strictly
      anaerobic bacteria that grow lithotrophically on H2 plus CO2 or on CO or
      heterotrophically on different substrates such as sugars, alcohols, aldehydes, or
      acids. Amino acids are rarely used. Here, we describe that the model acetogen
      Acetobacterium woodii can use alanine as the sole carbon and energy source, which
      is in contrast to the description of the type strain. The alanine degradation
      genes have been identified and characterized. A key to alanine degradation is an
      alanine dehydrogenase which has been characterized biochemically. The resulting
      pyruvate is further degraded to acetate by the known pathways involving the Wood
      Ljungdahl pathway. Our studies culminate in a metabolic and bioenergetic scheme
      for alanine-dependent acetogenesis in A. woodii IMPORTANCE Peptides and amino
      acids are widespread in nature, but there are only a few reports that
      demonstrated use of amino acids as carbon and energy sources by acetogenic
      bacteria, a central and important group in the anaerobic food web. Our finding
      that A. woodii can perform alanine oxidation coupled to reduction of carbon
      dioxide not only increases the number of substrates that can be used by this
      model acetogen but also raises the possibility that other acetogens may also be
      able to use alanine. Indeed, the alanine genes are also present in at least two
      more acetogens, for which growth on alanine has not been reported so far. Alanine
      may be a promising substrate for industrial fermentations, since acid formation
      goes along with the production of a base (NH3) and pH regulation is a minor
      issue.

PMID- 30242009
TI  - Single Nucleotide Polymorphism Genotyping Analysis Shows That Vaccination Can
      Limit the Number and Diversity of Recombinant Progeny of Infectious
      Laryngotracheitis Viruses from the United States.
AB  - Infectious laryngotracheitis (ILTV; Gallid alphaherpesvirus 1) causes mild to
      severe respiratory disease in poultry worldwide. Recombination in this virus
      under natural (field) conditions was first described in 2012 and more recently
      has been studied under laboratory conditions. Previous studies have revealed that
      natural recombination is widespread in ILTV and have also demonstrated that
      recombination between two attenuated ILTV vaccine strains generated highly
      virulent viruses that produced widespread disease within poultry flocks in
      Australia. In the United States, natural ILTV recombination has also been
      detected, but not as frequently as in Australia. To better understand
      recombination in ILTV strains originating from the United States, we developed a
      TaqMan single nucleotide polymorphism (SNP) genotyping assay to detect
      recombination between two virulent U.S. field strains of ILTV (63140 and 1874c5)
      under experimental in vivo conditions. We also tested the capacity of the Innovax
      ILT vaccine (a recombinant vaccine using herpesvirus of turkeys as a vector) and
      the Trachivax vaccine (a conventionally attenuated chicken embryo origin vaccine)
      to reduce recombination. The Trachivax vaccine prevented ILTV replication, and
      therefore recombination, in the trachea after challenge. The Innovax-ILT vaccine
      allowed the challenge viruses to replicate and to recombine, but at a
      significantly lower rate than in an unvaccinated group of birds. Our results
      demonstrate that the TaqMan SNP genotyping assay is a useful tool to study
      recombination between these ILTV strains and also show that vaccination can limit
      the number and diversity of recombinant progeny viruses.IMPORTANCE Recombination
      allows alphaherpesviruses to evolve over time and become more virulent.
      Historically, characterization of viral vaccines in poultry have mainly focused
      on limiting clinical disease, rather than limiting virus replication, but such
      approaches can allow field viruses to persist and evolve in vaccinated
      populations. In this study, we vaccinated chickens with Gallid alphaherpesvirus 1
      vaccines that are commercially available in the United States and then performed
      coinoculations with two field strains of virus to measure the ability of the
      vaccines to prevent field strains from replicating and recombining. We found that
      vaccination reduced viral replication, recombination, and diversity compared to
      those in unvaccinated chickens, although the extent to which this occurred
      differed between vaccines. We suggest that characterization of vaccines could
      include studies to examine the ability of vaccines to reduce viral recombination
      in order to limit the rise of new virulent field strains due to recombination,
      especially for those vaccines that are known not to prevent viral replication
      following challenge.

PMID- 30242012
TI  - Diagnosing opioid addiction in people with chronic pain.

PMID- 30242010
TI  - Cell Wall Glycans Mediate Recognition of the Dairy Bacterium Streptococcus
      thermophilus by Bacteriophages.
AB  - Receptors on the cell surfaces of bacterial hosts are essential during the
      infection cycle of bacteriophages. To date, the phage receptors of the industrial
      relevant dairy starter bacterium Streptococcus thermophilus remain elusive. Thus,
      we set out to identify cell surface structures that are involved in host
      recognition by dairy streptococcal phages. Five industrial S. thermophilus
      strains sensitive to different phages (pac type, cos type, and the new type 987),
      were selected to generate spontaneous bacteriophage-insensitive mutants (BIMs).
      Of these, approximately 50% were deselected as clustered regularly interspaced
      short palindromic repeat (CRISPR) mutants, while the other pool was further
      characterized to identify receptor mutants. On the basis of genome sequencing
      data, phage resistance in putative receptor mutants was attributed to nucleotide
      changes in genes encoding glycan biosynthetic pathways. Superresolution
      structured illumination microscopy was used to visualize the interactions between
      S. thermophilus and its phages. The phages were either regularly distributed
      along the cells or located at division sites of the cells. The cell wall
      structures mediating the latter type of phage adherence were further analyzed via
      phenotypic and biochemical assays. Altogether, our data suggested that phage
      adsorption to S. thermophilus is mediated by glycans associated with the
      bacterial cell surface. Specifically, the pac-type phage CHPC951 adsorbed to
      polysaccharides anchored to peptidoglycan, while the 987-type phage CHPC926
      recognized exocellular polysaccharides associated with the cell
      surface.IMPORTANCE Streptococcus thermophilus is widely used in starter cultures
      for cheese and yoghurt production. During dairy fermentations, infections of
      bacteria with bacteriophages result in acidification failures and a lower quality
      of the final products. An understanding of the molecular factors involved in
      phage-host interactions, in particular, the phage receptors in dairy bacteria, is
      a crucial step for developing better strategies to prevent phage infections in
      dairy plants.

PMID- 30242013
TI  - Correction for Diaz et al., "Specialized Proresolving Mediators Rescue Infant
      Mice from Lethal Citrobacter rodentium Infection and Promote Immunity against
      Reinfection".

PMID- 30242011
TI  - Meiotic Double-Strand Break Proteins Influence Repair Pathway Utilization.
AB  - Double-strand breaks (DSBs) are among the most deleterious lesions DNA can
      endure. Yet, DSBs are programmed at the onset of meiosis, and are required to
      facilitate appropriate reduction of ploidy in daughter cells. Repair of these
      breaks is tightly controlled to favor homologous recombination (HR)-the only
      repair pathway that can form crossovers. However, little is known about how the
      activities of alternative repair pathways are regulated at these stages. We
      discovered an unexpected synthetic interaction between the DSB machinery and
      strand-exchange proteins. Depleting the Caenorhabditis elegans DSB-promoting
      factors HIM-5 and DSB-2 suppresses the formation of chromosome fusions that arise
      in the absence of RAD-51 or other strand-exchange mediators. Our investigations
      reveal that nonhomologous and theta-mediated end joining (c-NHEJ and TMEJ,
      respectively) and single strand annealing (SSA) function redundantly to repair
      DSBs when HR is compromised, and that HIM-5 influences the utilization of TMEJ
      and SSA.

PMID- 30242014
TI  - Correction for Cobo et al., "Entamoeba histolytica Alters Ileal Paneth Cell
      Functions in Intact and Muc2 Mucin Deficiency".

PMID- 30242015
TI  - Correction for Clemons et al., "Cytosolic Delivery of Multidomain Cargos by the N
      Terminus of Pasteurella multocida Toxin".

PMID- 30242016
TI  - Sigma-1 receptor and amyotrophic lateral sclerosis.

PMID- 30242017
TI  - Nocturnal monitoring in epilepsy: Evidence mounts.

PMID- 30242018
TI  - Nocturnal supervision and SUDEP risk at different epilepsy care settings.
AB  - OBJECTIVE: To estimate the incidence of sudden unexpected death in epilepsy
      (SUDEP) in people with intellectual disabilities in residential care settings and
      to ascertain the effects of nocturnal seizures and nocturnal supervision on SUDEP
      risk. METHODS: We conducted a nested case-control study reviewing records of all
      people who died at 2 residential care settings over 25 years. Four controls per
      case were selected from the same population, matched on age (+/-5 years) and
      residential unit. Nocturnal supervision was graded in 3 categories: (1) no
      supervision; (2) a listening device or a roommate or physical checks at least
      every 15 minutes; and (3) 2 of the following: a listening device, roommate,
      additional device (bed motion sensor/video monitoring), or physical checks every
      15 minutes. Outcome measures were compared using Mann-Whitney U tests and Fisher
      exact tests. RESULTS: We identified 60 SUDEP cases and 198 matched controls.
      People who died of SUDEP were more likely to have nocturnal convulsive seizures
      in general (77% of cases vs 33% of controls, p < 0.001) and a higher frequency of
      nocturnal convulsive seizures. Total SUDEP incidence was 3.53/1,000 patient-years
      (95% confidence interval [CI] 2.73-4.53). The incidence differed among centers:
      2.21/1,000 patient-years (95% CI 1.49-3.27) vs 6.12/1,000 patient-years (95% CI
      4.40-8.52). There was no significant difference in nocturnal supervision among
      cases and controls, but there was a difference among centers: the center with a
      lowest grade of supervision had the highest incidence of SUDEP. CONCLUSIONS:
      Having nocturnal seizures, in particular convulsions, may increase SUDEP risk.
      Different levels of nocturnal supervision may account for some of the difference
      in incidence.

PMID- 30242019
TI  - Redesigning care: adapting new improvement methods to achieve person-centred
      care.

PMID- 30242020
TI  - NK Cell Education in Tumor Immune Surveillance: DNAM-1/KIR Receptor Ratios as
      Predictive Biomarkers for Solid Tumor Outcome.
AB  - Natural killer cell (NKc)-based therapies offer promising outcomes in patients
      with tumors, but they could improve with appropriate selection of donors and
      optimization of methods to expand NKcs in vitro Education through licensing
      interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) and
      NKG2A with their cognate HLA class-I ligands optimizes NKc functional competence.
      This work has evaluated the role of licensing interactions in NKc differentiation
      and the survival of cancer patients. We have analyzed KIR and KIR-ligand genes,
      and the expression of activating (CD16 and DNAM-1/CD226) and inhibitory (NKG2A
      and iKIRs) receptors on peripheral blood NKcs in 621 healthy controls and 249
      solid cancer patients (80 melanoma, 80 bladder, and 89 ovarian). Licensing
      interactions upregulated the expression of activating CD226, reduced that of iKIR
      receptors, and shifted the CD226/iKIR receptor ratio on NKc membranes to
      activating receptors. A high tumor burden decreased CD226 expression, reduced the
      ratio of CD226/iKIR, and negatively affected patient survival. The progression
      free survival (38.1 vs. 67.0 months, P < 0.002) and overall survival (56.3 vs.
      99.6 months, P < 0.00001) were significantly shorter in patients with lower
      expression of CD226 on NKcs. Hence, transformed cells can downmodulate these
      licensing-driven receptor rearrangements as a specific mechanism to escape NKc
      immune surveillance. Our results suggest the importance of the CD226/iKIR
      receptor ratio of NKcs induced by licensing interactions as critical determinants
      for solid cancer immune surveillance, and may provide predictive biomarkers for
      patient survival that may also improve the selection of donors for NKc
      immunotherapy.

PMID- 30242021
TI  - A High-Throughput Immune-Oncology Screen Identifies EGFR Inhibitors as Potent
      Enhancers of Antigen-Specific Cytotoxic T-lymphocyte Tumor Cell Killing.
AB  - We developed a screening assay in which luciferized ID8 expressing OVA was
      cocultured with transgenic CD8+ T cells specifically recognizing the model
      antigen in an H-2b-restricted manner. The assay was screened with a small
      molecule library to identify compounds that inhibit or enhance T cell-mediated
      killing of tumor cells. Erlotinib, an EGFR inhibitor, was the top compound that
      enhanced T-cell killing of tumor cells. Subsequent experiments with erlotinib and
      additional EGFR inhibitors validated the screen results. EGFR inhibitors
      increased both basal and IFNgamma-induced MHC class-I presentation, which
      enhanced recognition and lysis of tumor cell targets by CD8+ cytotoxic T
      lymphocytes. The ID8 cell line was also transduced to constitutively express
      Cas9, and a pooled CRISPR screen, utilizing the same target tumor cell/T-cell
      assay, identified single-guide (sg)RNAs targeting EGFR that sensitized tumor
      cells to T cell-mediated killing. Combination of PD-1 blockade with EGFR
      inhibition showed significant synergistic efficacy in a syngeneic model, further
      validating EGFR inhibitors as immunomodulatory agents that enhance checkpoint
      blockade. This assay can be screened in high-throughput with small-molecule
      libraries and genome-wide CRISPR/Cas9 libraries to identify both compounds and
      target genes, respectively, that enhance or inhibit T-cell recognition and
      killing of tumor cells. Retrospective analyses of squamous-cell head and neck
      cancer (SCCHN) patients treated with the combination of afatinib and
      pembrolizumab demonstrated a rate of clinical activity exceeding that of each
      single agent. Prospective clinical trials evaluating the combination of an EGFR
      inhibitor and PD-1 blockade should be conducted.

PMID- 30242022
TI  - Immunotherapy Targeting HPV16/18 Generates Potent Immune Responses in HPV
      Associated Head and Neck Cancer.
AB  - Purpose: Clinical responses with programmed death (PD-1) receptor-directed
      antibodies occur in about 20% of patients with advanced head and neck squamous
      cell cancer (HNSCCa). Viral neoantigens, such as the E6/E7 proteins of HPV16/18,
      are attractive targets for therapeutic immunization and offer an immune
      activation strategy that may be complementary to PD-1 inhibition.Experimental
      Design: We report phase Ib/II safety, tolerability, and immunogenicity results of
      immunotherapy with MEDI0457 (DNA immunotherapy targeting HPV16/18 E6/E7 with IL12
      encoding plasmids) delivered by electroporation with CELLECTRA constant current
      device. Twenty-two patients with locally advanced, p16+ HNSCCa received
      MEDI0457.Results: MEDI0457 was associated with mild injection site reactions, but
      no treatment-related grade 3-5 adverse events (AE) were noted. Eighteen of 21
      evaluable patients showed elevated antigen-specific T-cell activity by IFNgamma
      ELISpot, and persistent cellular responses surpassing 100 spot-forming units
      (SFUs)/106 peripheral blood mononuclear cells (PBMCs) were noted out to 1 year.
      Induction of HPV-specific CD8+ T cells was observed. MEDI0457 shifted the
      CD8+/FoxP3+ ratio in 4 of 5 post immunotherapy tumor samples and increased the
      number of perforin+ immune infiltrates in all 5 patients. One patient developed
      metastatic disease and was treated with anti-PD-1 therapy with a rapid and
      durable complete response. Flow-cytometric analyses revealed induction of HPV16
      specific PD-1+ CD8+ T cells that were not found prior to MEDI0547 (0% vs.
      1.8%).Conclusions: These data demonstrate that MEDI0457 can generate durable
      HPV16/18 antigen-specific peripheral and tumor immune responses. This approach
      may be used as a complementary strategy to PD-1/PD-L1 inhibition in HPV
      associated HNSCCa to improve therapeutic outcomes. Clin Cancer Res; 1-15. (c)2018
      AACR.

PMID- 30242023
TI  - Multimodal Meta-Analysis of 1,494 Hepatocellular Carcinoma Samples Reveals
      Significant Impact of Consensus Driver Genes on Phenotypes.
AB  - Although driver genes in hepatocellular carcinoma (HCC) have been investigated in
      various previous genetic studies, prevalence of key driver genes among
      heterogeneous populations is unknown. Moreover, the phenotypic associations of
      these driver genes are poorly understood. This report aims to reveal the
      phenotypic impacts of a group of consensus driver genes in HCC. We used MutSigCV
      and OncodriveFM modules implemented in the IntOGen pipeline to identify consensus
      driver genes across six HCC cohorts comprising 1,494 samples in total. To access
      their global impacts, we used The Cancer Genome Atlas (TCGA) mutations and copy
      number variations to predict the transcriptomics data, under generalized linear
      models. We further investigated the associations of the consensus driver genes to
      patient survival, age, gender, race, and risk factors. We identify 10 consensus
      driver genes across six HCC cohorts in total. Integrative analysis of driver
      mutations, copy-number variations, and transcriptomic data reveals that these
      consensus driver mutations and their copy-number variations are associated with a
      majority (62.5%) of the mRNA transcriptome but only a small fraction (8.9%) of
      miRNAs. Genes associated with TP53, CTNNB1, and ARID1A mutations contribute to
      the tripod of most densely connected pathway clusters. These driver genes are
      significantly associated with patients' overall survival. Some driver genes are
      significantly linked to HCC gender (CTNNB1, ALB, TP53, and AXIN1), race (TP53 and
      CDKN2A), and age (RB1) disparities. This study prioritizes a group of consensus
      drivers in HCC, which collectively show vast impacts on the phenotypes. These
      driver genes may warrant as valuable therapeutic targets of HCC. Clin Cancer Res;
      1-10. (c)2018 AACR.

PMID- 30242024
TI  - CDK4/6 Inhibitor as a Novel Therapeutic Approach for Advanced Bladder Cancer
      Independently of RB1 Status.
AB  - Purpose: Bladder cancer is a clinical and social problem due to its high
      incidence and recurrence rates. It frequently appears in elderly patients showing
      other medical comorbidities that hamper the use of standard chemotherapy. We
      evaluated the activity of CDK4/6 inhibitor as a new therapy for patients unfit
      for cisplatin (CDDP).Experimental Design: Bladder cancer cell lines were tested
      for in vitro sensitivity to CDK4/6 inhibition. A novel metastatic bladder cancer
      mouse model was developed and used to test its in vivo activity.Results: Cell
      lines tested were sensitive to CDK4/6 inhibition, independent on RB1 gene status.
      Transcriptome analyses and knockdown experiments revealed a major role for FOXM1
      in this response. CDK4/6 inhibition resulted in reduced FOXM1 phosphorylation in
      vitro and in vivo and showed synergy with CDDP, allowing a significant tumor
      regression. FOXM1 exerted important oncogenic roles in bladder
      cancer.Conclusions: CDK4/6 inhibitors, alone or in combination, are a novel
      therapeutic strategy for patients with advanced bladder cancer previously
      classified as unfit for current treatment options. Clin Cancer Res; 1-13. (c)2018
      AACR.

PMID- 30242026
TI  - BK Virus Nephropathy.

PMID- 30242025
TI  - MicroRNA-21 and Venous Neointimal Hyperplasia of Dialysis Vascular Access.
AB  - BACKGROUND AND OBJECTIVES: There is increasing evidence that microRNAs (miRNAs)
      play crucial roles in the regulation of neointima formation. However, the
      translational evidence of the role of miRNAs in dialysis vascular access is
      limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: miRNA expression in
      tissues was assessed by using venous tissues harvested from ten patients on
      dialysis who received revision or removal surgery, and ten patients who were
      predialysis and received creation surgery of arteriovenous fistulas served as
      controls. To extend these findings, 60 patients who received angioplasty of
      dialysis access were enrolled and the levels of circulating miRNAs were
      determined before and 2 days after angioplasty. Clinical follow-up was continued
      monthly for 6 months. The primary outcome of angioplasty cohort was target lesion
      restenosis within 6 months after angioplasty. RESULTS: In the surgery cohort, the
      expressions of miR-21, miR-130a, and miR-221 were upregulated in stenotic
      tissues, whereas those of miR-133 and miR-145 were downregulated. In situ
      hybridization revealed similar expression patterns of these miRNAs, localized
      predominantly in the neointima region. Twenty eight patients in the angioplasty
      cohort developed restenosis within 6 months. The levels of circulating miR-21,
      miR-130a, miR-221, miR-133, and miR-145 significantly increased 2 days after
      angioplasty. Kaplan-Meier plots showed that patients with an increase of miR-21
      expression level >0.35 have a higher risk of patency loss (hazard ratio, 4.45;
      95% confidence interval, 1.68 to 11.7). In a multivariable analysis,
      postangioplasty increase of miR-21 expression was independently associated with
      restenosis (hazard ratio, 1.20; 95% confidence interval, 1.07 to 1.35 per one
      unit increase of miR-21 expression level; P=0.001). CONCLUSIONS: Certain miRNAs
      are differentially expressed in the stenotic venous segments of dialysis
      accesses. An increase in blood miR-21 level with angioplasty is associated with a
      higher risk of restenosis.

PMID- 30242028
TI  - Defining Hypertension: Role of New Trials and Guidelines.

PMID- 30242027
TI  - Kidney Function Decline in Patients with CKD and Untreated Hepatitis C Infection.
AB  - BACKGROUND AND OBJECTIVES: Studies evaluating the role of hepatitis C viral (HCV)
      infection on the progression of CKD are few and conflicting. Therefore, we
      evaluated the association of untreated HCV on kidney function decline in patients
      with stage 3-5 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This
      retrospective cohort study included members of Kaiser Permanente Southern
      California and Kaiser Permanente Mid-Atlantic States aged >=18 years, with
      incident HCV and CKD diagnoses from January 1, 2004 to December 31, 2014. We used
      generalized estimating equations to compare the rate of change in eGFR between
      those with HCV and CKD versus CKD alone, adjusting for covariates. Cox
      proportional hazards models compared the risk of 25% decrease in eGFR and ESKD
      (defined as progression to eGFR<15 ml/min per 1.73 m2 on two or more occasions,
      at least 90 days apart) in those with HCV and CKD versus CKD alone, adjusting for
      covariates. RESULTS: We identified 151,974 patients with CKD only and 1603
      patients with HCV and CKD who met the study criteria. The adjusted annual decline
      of eGFR among patients with HCV and CKD was greater by 0.58 (95% confidence
      interval [95% CI], 0.31 to 0.84) ml/min per 1.73 m2, compared with that in the
      CKD-only population (HCV and CKD, -1.61; 95% CI, -1.87 to -1.35 ml/min; CKD only,
      -1.04; 95% CI, -1.06 to -1.01 ml/min). Adjusted for covariates, the hazard for a
      25% decline in eGFR and for ESKD were 1.87 (95% CI, 1.75 to 2.00) and 1.93 (95%
      CI, 1.64 to 2.27) times higher among those with HCV and CKD, respectively,
      compared with those with CKD only. CONCLUSIONS: Untreated HCV infection was
      associated with greater kidney function decline in patients with stage 3-5 CKD.

PMID- 30242030
TI  - Coffee consumption and gout: a Mendelian randomisation study.

PMID- 30242029
TI  - Acute Kidney Injury in Children with Kidney Transplantation.
AB  - BACKGROUND AND OBJECTIVES: AKI is associated with progression of CKD. Little is
      known about AKI after kidney transplantation in pediatric recipients. We aim to
      describe the epidemiology, risk factors, consequences, and outcomes of AKI in
      this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a
      retrospective longitudinal analysis of pediatric kidney transplant recipients
      followed at The Hospital for Sick Children (Toronto, Canada) from 2001 to 2012.
      AKI was defined as an increase in serum creatinine >=1.5 times baseline, and a
      rise of serum creatinine >=1.25 but <1.5 times baseline defined subacute AKI.
      RESULTS: Of 179 children, 122 were eligible for analysis. At baseline (3 months
      post-transplant), median age of the children was 13 years old (interquartile
      range, 9-16 years old), and 53% had CKD stage 2. Congenital anomalies of the
      kidney and urinary tract accounted for 46% of children. Over the study period (12
      years), the incidence of AKI was 37% (n=45 children), and 65% (79 children)
      experienced subacute AKI. Twenty-seven percent (33 children) did not develop AKI
      or subacute AKI. The main causes of AKI were infections other than urinary tract
      infections, rejection, and urinary tract infections. In a multivariable Poisson
      regression analysis, independent risk factors for AKI included younger age,
      girls, grafts from deceased donors, and lower baseline eGFR. AKI was
      significantly associated with lower long-term GFR and graft loss independent of
      rejection episodes. Moreover, subacute AKI was associated with progression of
      CKD. CONCLUSIONS: AKI and subacute AKI were common after pediatric kidney
      transplantation, and they were associated with graft loss, lower eGFR, and more
      rapid progression of CKD.

PMID- 30242031
TI  - Immune checkpoint inhibitor rechallenge in patients with immune-related myositis.

PMID- 30242032
TI  - Evaluation of retinal microvascular density in patients affected by systemic
      lupus erythematosus: an optical coherence tomography angiography study.

PMID- 30242033
TI  - Prevalence and incidence of psoriasis and psoriatic arthritis.

PMID- 30242035
TI  - GPs can expect to be sued once every 10 years, MDU warns.

PMID- 30242034
TI  - Cell polarity and adherens junction formation inhibit epithelial Fas cell death
      receptor signaling.
AB  - Finely tuned regulation of epithelial cell death maintains tissue integrity and
      homeostasis. At the cellular level, life and death decisions are controlled by
      environmental stimuli such as the activation of death receptors. We show that
      cell polarity and adherens junction formation prevent proapoptotic signals
      emanating from the Fas death receptor. Fas is sequestered in E-cadherin actin
      based adhesion structures that are less able to induce downstream apoptosis
      signaling. Using a proteomic-based approach, we find that the polarity molecule
      Dlg1 interacts with the C-terminal PDZ-binding site in Fas and that this
      interaction decreases formation of the death-inducing complex upon engagement
      with Fas ligand (FasL), thus acting as an additional cell death protection
      mechanism. We propose that E-cadherin and Dlg1 inhibit FasL-induced cell death by
      two complementary but partially independent mechanisms that help to maintain
      epithelial homeostasis by protecting normal polarized epithelia from apoptosis.
      When polarity is lost, the Fas-cadherin-Dlg1 antiapoptotic complex is disrupted,
      and FasL can promote the elimination of compromised nonpolarized cells.

PMID- 30242036
TI  - Illuminating cell signaling with genetically encoded FRET biosensors in adult
      mouse cardiomyocytes.
AB  - FRET-based biosensor experiments in adult cardiomyocytes are a powerful way of
      dissecting the spatiotemporal dynamics of the complicated signaling networks that
      regulate cardiac health and disease. However, although much information has been
      gleaned from FRET studies on cardiomyocytes from larger species, experiments on
      adult cardiomyocytes from mice have been difficult at best. Thus the large
      variety of genetic mouse models cannot be easily used for this type of study.
      Here we develop cell culture conditions for adult mouse cardiomyocytes that
      permit robust expression of adenoviral FRET biosensors and reproducible FRET
      experimentation. We find that addition of 6.25 uM blebbistatin or 20 uM (S)-nitro
      blebbistatin to a minimal essential medium containing 10 mM HEPES and 0.2% BSA
      maintains morphology of cardiomyocytes from physiological, pathological, and
      transgenic mouse models for up to 50 h after adenoviral infection. This provides
      a 10-15-h time window to perform reproducible FRET readings using a variety of
      CFP/YFP sensors between 30 and 50 h postinfection. The culture is applicable to
      cardiomyocytes isolated from transgenic mouse models as well as models with
      cardiac diseases. Therefore, this study helps scientists to disentangle
      complicated signaling networks important in health and disease of cardiomyocytes.

PMID- 30242037
TI  - Blue Light Regulates Secondary Cell Wall Thickening via MYC2/MYC4 Activation of
      the NST1-Directed Transcriptional Network in Arabidopsis.
AB  - Secondary cell walls (SCWs) are formed in some specific types of plant cells,
      providing plants with mechanical strength. During plant growth and development,
      formation of secondary cell walls is regulated by various developmental and
      environmental signals. The underlying molecular mechanisms are poorly understood.
      In this study, we analyzed the blue light receptor cryptochrome1 (cry1) mutant of
      Arabidopsis thaliana for its SCW phenotypes. During inflorescence stem growth,
      SCW thickening in the vasculature was significantly affected by blue light. cry1
      plants displayed a decline of SCW thickening in fiber cells, while CRY1
      overexpression led to enhanced SCW formation. Transcriptome analysis indicated
      that the reduced SCW thickening was associated with repression of the NST1
      directed transcription regulatory networks. Further analyses revealed that the
      expression of MYC2/MYC4 that is induced by blue light activates the
      transcriptional network underlying SCW thickening. The activation is caused by
      direct binding of MYC2/MYC4 to the NST1 promoter. This study demonstrates that
      SCW thickening in fiber cells is regulated by a blue light signal that is
      mediated through MYC2/MYC4 activation of NST1-directed SCW formation in
      Arabidopsis.

PMID- 30242038
TI  - The E3 Ubiquitin Ligase HAF1 Modulates Circadian Accumulation of EARLY FLOWERING3
      to Control Heading Date in Rice under Long-Day Conditions.
AB  - The ubiquitin 26S proteasome system (UPS) is critical for enabling plants to
      alter their proteomes to integrate internal and external signals for the
      photoperiodic induction of flowering. We previously demonstrated that HAF1, a
      C3HC4 RING domain-containing E3 ubiquitin ligase, is essential to precisely
      modulate the timing of Heading Date1 accumulation and to ensure appropriate
      photoperiodic responses under short-day conditions in rice (Oryza sativa).
      However, how HAF1 mediates flowering under long-day conditions remains unknown.
      In this study, we show that OsELF3 (EARLY FLOWERING3) is the direct substrate of
      HAF1 for ubiquitination in vitro and in vivo. HAF1 is required for maintaining
      the circadian rhythm of OsELF3 accumulation during photoperiodic responses in
      rice. In addition, the haf1 oself3 double mutant headed as late as oself3 plants
      under long-day conditions. An amino acid variation (L558S) within the interaction
      domain of OsELF3 with HAF1 greatly contributes to the variation in heading date
      among japonica rice accessions. The japonica accessions carrying the OsELF3(L)
      type allele are found at higher latitudes, while varieties carrying the OsELF3(S)
      type allele are found at lower latitudes. Taken together, our findings suggest
      that HAF1 precisely modulates the diurnal rhythm of OsELF3 accumulation to ensure
      the appropriate heading date in rice.

PMID- 30242040
TI  - A widely used sampling device in colorectal cancer screening programmes allows
      for large-scale microbiome studies.

PMID- 30242039
TI  - The ZmbZIP22 Transcription Factor Regulates 27-kD gamma-Zein Gene Transcription
      during Maize Endosperm Development.
AB  - Zeins are the most abundant storage proteins in maize (Zea mays) kernels, thereby
      affecting the nutritional quality and texture of this crop. 27-kD gamma-zein is
      highly expressed and plays a crucial role in protein body formation. Several
      transcription factors (TFs) (O2, PBF1, OHP1, and OHP2) regulate the expression of
      the 27-kD gamma-zein gene, but the complexity of its transcriptional regulation
      is not fully understood. Here, using probe affinity purification and mass
      spectrometry analysis, we identified ZmbZIP22, a TF that binds to the 27-kD gamma
      zein promoter. ZmbZIP22 is a bZIP-type TF that is specifically expressed in
      endosperm. ZmbZIP22 bound directly to the ACAGCTCA box in the 27-kD gamma-zein
      promoter and activated its expression in wild tobacco (Nicotiana benthamiana)
      cells. 27-kD gamma-zein gene expression was significantly reduced in CRISPR/Cas9
      generated zmbzip22 mutants. ChIP-seq (chromatin immunoprecipitation coupled to
      high-throughput sequencing) confirmed that ZmbZIP22 binds to the 27-kD gamma-zein
      promoter in vivo and identified additional direct targets of ZmbZIP22. ZmbZIP22
      can interact with PBF1, OHP1, and OHP2, but not O2. Transactivation assays using
      various combinations of these TFs revealed multiple interaction modes for the
      transcriptional activity of the 27-kD gamma-zein promoter. Therefore, ZmbZIP22
      regulates 27-kD gamma-zein gene expression together with other known TFs.

PMID- 30242042
TI  - Mallostery: Filling a niche between quality and metabolic control.
AB  - To be, or not to be ... What determines the destruction of a protein in response
      to metabolic cues? In the current issue of JBC, Wangeline and Hampton shed new
      light on this existential question by studying the classic case of HMGCR (Hmg2 in
      yeast), the rate-limiting step in sterol synthesis, and find a metabolic cue that
      causes "allosteric misfolding" and subsequent destruction of the protein, a
      concept they name mallostery.

PMID- 30242041
TI  - Correction: Disulfide-crosslink scanning reveals prion-induced conformational
      changes and prion strain-specific structures of the pathological prion protein
      PrPSc.

PMID- 30242043
TI  - Tobacco-specific nitrosamines (TSNA) in heated tobacco product IQOS.

PMID- 30242044
TI  - Philip Morris International-funded 'Foundation for a Smoke-Free World': analysing
      its claims of independence.
AB  - The Foundation for a Smoke-Free World was launched in September 2017 with an
      announced 12-year funding commitment of $1 billion from Philip Morris
      International (PMI). The Foundation claims that its governing documents
      (certificate of incorporation, bylaws and a pledge agreement) ensure that it has
      an independent research agenda and stringent protections from conflicts of
      interest. We analysed the text of these governing documents. Their provisions
      have multiple loopholes, particularly regarding conflicts of interest. Further,
      these documents cannot substitute for other important documentation such as
      information about PMI's internal business case for investing $1 billion in the
      Foundation, an unwaivable conflict of interest policy, annual disclosure
      statements, copies of pre-Foundation establishment correspondence between key
      individuals, all signed contracts or salary information, none of which, as of
      July 2018, the Foundation has made publicly available. Even if these were
      released, however, it is problematic that the Foundation's fundamental purpose
      was decided on and its leader selected following a tobacco company-paid,
      privately negotiated arrangement with the Foundation's president. It cannot be
      regarded as independent.

PMID- 30242045
TI  - Theta Bursts Precede, and Spindles Follow, Cortical and Thalamic Downstates in
      Human NREM Sleep.
AB  - Since their discovery, slow oscillations have been observed to group spindles
      during non-REM sleep. Previous studies assert that the slow-oscillation downstate
      (DS) is preceded by slow spindles (10-12 Hz) and followed by fast spindles (12-16
      Hz). Here, using both direct transcortical recordings in patients with
      intractable epilepsy (n = 10, 8 female), as well as scalp EEG recordings from a
      healthy cohort (n = 3, 1 female), we find in multiple cortical areas that both
      slow and fast spindles follow the DS. Although discrete oscillations do precede
      DSs, they are theta bursts (TBs) centered at 5-8 Hz. TBs were more pronounced for
      DSs in NREM stage 2 (N2) sleep compared with N3. TB with similar properties occur
      in the thalamus, but unlike spindles they have no clear temporal relationship
      with cortical TB. These differences in corticothalamic dynamics, as well as
      differences between spindles and theta in coupling high-frequency content, are
      consistent with NREM theta having separate generative mechanisms from spindles.
      The final inhibitory cycle of the TB coincides with the DS peak, suggesting that
      in N2, TB may help trigger the DS. Since the transition to N1 is marked by the
      appearance of theta, and the transition to N2 by the appearance of DS and thus
      spindles, a role of TB in triggering DS could help explain the sequence of
      electrophysiological events characterizing sleep. Finally, the coordinated
      appearance of spindles and DSs are implicated in memory consolidation processes,
      and the current findings redefine their temporal coupling with theta during NREM
      sleep.SIGNIFICANCE STATEMENT Sleep is characterized by large slow waves which
      modulate brain activity. Prominent among these are downstates (DSs), periods of a
      few tenths of a second when most cells stop firing, and spindles, oscillations at
      ~12 times a second lasting for ~a second. In this study, we provide the first
      detailed description of another kind of sleep wave: theta bursts (TBs), a brief
      oscillation at ~six cycles per second. We show, recording during natural sleep
      directly from the human cortex and thalamus, as well as on the scalp, that TBs
      precede, and spindles follow DSs. TBs may help trigger DSs in some circumstances,
      and could organize cortical and thalamic activity so that memories can be
      consolidated during sleep.

PMID- 30242047
TI  - Molecular and Genetic Evidence for the PDGFRalpha-Independent Population of
      Oligodendrocyte Progenitor Cells in the Developing Mouse Brain.
AB  - PDGFRalpha, specifically expressed by immature oligodendrocyte progenitor cells
      (OPCs) in the CNS, plays a critical role in OPC proliferation and migration.
      However, it has been uncertain whether all cells of oligodendrocyte lineage are
      derived from the PDGFRalpha-expressing OPCs. In the present study, we uncovered a
      PDGFRalpha-independent oligodendrocyte lineage in the developing cortex. This OPC
      subpopulation originates from the local ventricular/subventricular zone after
      birth and contributes to the earliest mature oligodendrocytes in the cortex.
      PDGFRalpha signaling does not regulate the generation and differentiation of
      cortical OPCs. Fate-mapping studies in the PDGFRalphaCreER; Sox10-GFP/tdTom
      double-transgenic mice of either sex have further corroborated the PDGFRalpha
      independent oligodendrocyte lineage. This study provides additional missing
      genetic evidence for PDGFRalpha-independent oligodendrocyte lineage in the
      developing hindbrain.SIGNIFICANCE STATEMENT This is the first report of a
      subpopulation of oligodendrocyte lineage in the developing mouse cortex
      independent of PDGFRalpha signaling. These oligodendrocyte progenitor cells are
      generated from the local ventral ventricular zone/subventricular zone after
      birth, and contribute to the earliest mature oligodendrocytes in the cortex.

PMID- 30242046
TI  - Convergent Metabotropic Signaling Pathways Inhibit SK Channels to Promote
      Synaptic Plasticity in the Hippocampus.
AB  - Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is
      tightly regulated by postsynaptic small conductance (SK) channels that restrict
      NMDA receptor activity. SK channels are themselves modulated by G-protein-coupled
      signaling pathways, but it is not clear under what conditions these are activated
      to enable synaptic plasticity. Here, we show that muscarinic M1 receptor (M1R)
      and type 1 metabotropic glutamate receptor (mGluR1) signaling pathways, which are
      known to inhibit SK channels and thereby disinhibit NMDA receptors, converge to
      facilitate spine calcium transients during the induction of long-term
      potentiation (LTP) at hippocampal Schaffer collateral synapses onto CA1 pyramidal
      neurons of male rats. Furthermore, mGluR1 activation is required for LTP induced
      by reactivated place-cell firing patterns that occur in sharp-wave ripple events
      during rest or sleep. In contrast, M1R activation is required for LTP induced by
      place-cell firing patterns during exploration. Thus, we describe a common
      mechanism that enables synaptic plasticity during both encoding and consolidation
      of memories within hippocampal circuits.SIGNIFICANCE STATEMENT Memory ensembles
      in the hippocampus are formed during active exploration and consolidated during
      rest or sleep. These two distinct phases each require strengthening of synaptic
      connections by long-term potentiation (LTP). The neuronal activity patterns in
      each phase are very different, which makes it hard to map generalized rules for
      LTP induction onto both formation and consolidation phases. In this study, we
      show that inhibition of postsynaptic SK channels is a common necessary feature of
      LTP induction and that SK channel inhibition is achieved by separate but
      convergent metabotropic signaling pathways. Thus, we reveal a common mechanism
      for enabling LTP under distinct behavioral conditions.

PMID- 30242048
TI  - Genomic Analyses of Visual Cognition: Perceptual Rivalry and Top-Down Control.
AB  - Visual cognition in humans has traditionally been studied with cognitive
      behavioral methods and brain imaging, but much less with genetic methods.
      Perceptual rivalry, an important phenomenon in visual cognition, is the
      spontaneous perceptual alternation that occurs between two distinct
      interpretations of a physically constant visual stimulus (e.g., binocular rivalry
      stimuli) or a perceptually ambiguous stimulus (e.g., the Necker cube). The
      switching rate varies dramatically across individuals and can be voluntarily
      modulated by observers. Here, we adopted a genomic approach to systematically
      investigate the genetics underlying binocular rivalry, Necker cube rivalry and
      voluntary modulation of Necker cube rivalry in young Chinese adults (Homo
      sapiens, 81% female, 20 +/- 1 years old) at multiple levels, including common
      single nucleotide polymorphism (SNP)-based heritability estimation, SNP-based
      genome-wide association study (GWAS), gene-based analysis, and pathway analysis.
      We performed a pilot GWAS in 2441 individuals and replicated it in an independent
      cohort of 943 individuals. Common SNP-based heritability was estimated to be 25%
      for spontaneous perceptual rivalry. SNPs rs184765639 and rs75595941 were
      associated with voluntary modulation, and imaging data suggested genotypic
      difference of rs184765639 in the surface area of the left caudal-middle frontal
      cortex. Additionally, converging evidence from multilevel analyses associated
      genes such as PRMT1 with perceptual switching rate, and MIR1178 with voluntary
      modulation strength. In summary, this study discovered specific genetic
      contributions to perceptual rivalry and its voluntary modulation in human beings.
      These findings may promote our understanding of psychiatric disorders, as
      perceptual rivalry is a potential psychiatric biomarker.SIGNIFICANCE STATEMENT
      Perceptual rivalry is an important visual phenomenon in which our perception of a
      physically constant visual input spontaneously switches between two different
      states. There are individual variations in perceptual switching rate and
      voluntary modulation strength. Our genomic analyses reveal several loci
      associated with these two kinds of variation. Because perceptual rivalry is
      thought to be relevant to and potentially an endophenotype for psychiatric
      disorders, these results may help understand not only visual cognition, but also
      psychiatric disorders.

PMID- 30242050
TI  - Emergence of Binocular Disparity Selectivity through Hebbian Learning.
AB  - Neural selectivity in the early visual cortex strongly reflects the statistics of
      our environment (Barlow, 2001; Geisler, 2008). Although this has been described
      extensively in literature through various encoding hypotheses (Barlow and
      Foldiak, 1989; Atick and Redlich, 1992; Olshausen and Field, 1996), an
      explanation as to how the cortex might develop the computational architecture to
      support these encoding schemes remains elusive. Here, using the more realistic
      example of binocular vision as opposed to monocular luminance-field images, we
      show how a simple Hebbian coincidence-detector is capable of accounting for the
      emergence of binocular, disparity selective, receptive fields. We propose a model
      based on spike timing-dependent plasticity, which not only converges to realistic
      single-cell and population characteristics, but also demonstrates how known
      biases in natural statistics may influence population encoding and downstream
      correlates of behavior. Furthermore, we show that the receptive fields we obtain
      are closer in structure to electrophysiological data reported in macaques than
      those predicted by normative encoding schemes (Ringach, 2002). We also
      demonstrate the robustness of our model to the input dataset, noise at various
      processing stages, and internal parameter variation. Together, our modeling
      results suggest that Hebbian coincidence detection is an important computational
      principle and could provide a biologically plausible mechanism for the emergence
      of selectivity to natural statistics in the early sensory cortex.SIGNIFICANCE
      STATEMENT Neural selectivity in the early visual cortex is often explained
      through encoding schemes that postulate that the computational aim of early
      sensory processing is to use the least possible resources (neurons, energy) to
      code the most informative features of the stimulus (information efficiency). In
      this article, using stereo images of natural scenes, we demonstrate how a simple
      Hebbian rule can lead to the emergence of a disparity-selective neural population
      that not only shows realistic single-cell and population tunings, but also
      demonstrates how known biases in natural statistics may influence population
      encoding and downstream correlates of behavior. Our approach allows us to view
      early neural selectivity, not as an optimization problem, but as an emergent
      property driven by biological rules of plasticity.

PMID- 30242051
TI  - Sox14 Is Required for a Specific Subset of Cerebello-Olivary Projections.
AB  - We identify Sox14 as an exclusive marker of inhibitory projection neurons in the
      lateral and interposed, but not the medial, cerebellar nuclei. Sox14+ neurons
      make up ~80% of Gad1+ neurons in these nuclei and are indistinguishable by soma
      size from other inhibitory neurons. All Sox14+ neurons of the lateral and
      interposed cerebellar nuclei are generated at approximately E10/10.5 and extend
      long-range, predominantly contralateral projections to the inferior olive. A
      small Sox14+ population in the adjacent vestibular nucleus "Y" sends an
      ipsilateral projection to the oculomotor nucleus. Cerebellar Sox14+ and
      glutamatergic projection neurons assemble in non-overlapping populations at the
      nuclear transition zone, and their integration into a coherent nucleus depends on
      Sox14 function. Targeted ablation of Sox14+ cells by conditional viral expression
      of diphtheria toxin leads to significantly impaired motor learning. Contrary to
      expectations, associative learning is unaffected by unilateral Sox14+ neuron
      elimination in the interposed and lateral nuclei.SIGNIFICANCE STATEMENT The
      cerebellar nuclei are central to cerebellar function, yet how they modulate and
      process cerebellar inputs and outputs is still primarily unknown. Our study gives
      a direct insight into how nucleo-olivary projection neurons are generated, their
      projections, and their function in an intact behaving mouse. These neurons play a
      critical conceptual role in all models of cerebellar function, and this study
      represents the first specific analysis of their molecular identity and function
      and offers a powerful model for future investigation of cerebellar function in
      motor control and learning.

PMID- 30242052
TI  - The First Annual Meeting of the Society for Neuroscience, 1971: Reflections
      Approaching the 50th Anniversary of the Society's Formation.
AB  - The formation of the Society for Neuroscience in 1969 was a scientific landmark,
      remarkable for the conceptual transformation it represented by uniting all fields
      touching on the nervous system. The scientific program of the first annual
      meeting of the Society for Neuroscience, held in Washington, DC in 1971, is
      summarized here. By reviewing the scientific program from the vantage point of
      the 50th anniversary of the Society for Neuroscience, the trajectory of research
      now and into the future can be tracked to its origins, and the impact that the
      founding of the Society has had on basic and biomedical science is evident. The
      broad foundation of the Society was firmly cast at this first meeting, which
      embraced the full spectrum of science related to the nervous system, emphasized
      the importance of public education, and attracted the most renowned scientists of
      the day who were drawn together by a common purpose and eagerness to share
      research and ideas. Some intriguing areas of investigation discussed at this
      first meeting blossomed into new branches of research that flourish today, but
      others dwindled and have been largely forgotten. Technological developments and
      advances in understanding of brain function have been profound since 1971, but
      the success of the first meeting demonstrates how uniting scientists across
      diversity fueled prosperity of the Society and propelled the vigorous advancement
      of science.

PMID- 30242053
TI  - The Time Course of Target Template Activation Processes during Preparation for
      Visual Search.
AB  - Search for target objects in visual scenes is guided by mental representations of
      target features (attentional templates). However, it is unknown when such
      templates are activated during each search episode and whether this can be
      controlled by temporal expectations. We used electrophysiological measures to
      track search template activation processes in real time. In three experiments,
      female and male humans searched for a color-defined target object in search
      displays where targets were accompanied by distractors in different nontarget
      colors. Brief task-irrelevant color singleton probes that matched the target
      template were flashed rapidly (every 200 ms) throughout each block. Probes
      presented at times when the target template is active should capture attention,
      whereas probes presented at other times should not. To assess this, N2pc
      components were measured as markers of attentional capture, separately for probes
      at each successive temporal position between two search displays. Results
      demonstrated that search templates were active from ~1000 ms before the arrival
      of the next search display, and were deactivated after each search episode, even
      when the preceding search display did not contain a target object. Templates were
      activated later when the predictable interval between search displays was
      increased. Results demonstrate that search templates are not continuously active
      but are transiently activated during the preparation for each new search episode.
      These activation states are regulated in a top-down fashion by temporal
      expectations about when an attentional template will become task
      relevant.SIGNIFICANCE STATEMENT It is often assumed that observers prepare for a
      visual search task by activating mental representations of search target objects
      (attentional templates). However, the time course of such template activation
      processes is completely unknown. By using a new sequential probe presentation
      technique and electrophysiological measures of attentional processing, we
      demonstrate that target templates are rapidly activated and deactivated before
      and after each successive search display, and that these template activation
      states are tuned to observers' temporal expectations. These results provide novel
      insights into the temporal dynamics of cognitive control processes in visual
      attention. They show that attentional templates for visual search are preparatory
      states that are activated in a transient fashion before each new search episode.

PMID- 30242049
TI  - Angiopoietin/Tie2 Axis Regulates the Age-at-Injury Cerebrovascular Response to
      Traumatic Brain Injury.
AB  - Although age-at-injury influences chronic recovery from traumatic brain injury
      (TBI), the differential effects of age on early outcome remain understudied.
      Using a male murine model of moderate contusion injury, we investigated the
      underlying mechanism(s) regulating the distinct response between juvenile and
      adult TBI. We demonstrate similar biomechanical and physical properties of naive
      juvenile and adult brains. However, following controlled cortical impact (CCI),
      juvenile mice displayed reduced cortical lesion formation, cell death, and
      behavioral deficits at 4 and 14 d. Analysis of high-resolution laser Doppler
      imaging showed a similar loss of cerebral blood flow (CBF) in the ipsilateral
      cortex at 3 and 24 h post-CCI, whereas juvenile mice showed enhanced subsequent
      restoration at 2-4 d compared with adults. These findings correlated with reduced
      blood-brain barrier (BBB) disruption and increased perilesional vessel density.
      To address whether an age-dependent endothelial cell (EC) response affects vessel
      stability and tissue outcome, we magnetically isolated CD31+ ECs from sham and
      injured cortices and evaluated mRNA expression. Interestingly, we found increased
      transcripts for BBB stability-related genes and reduced expression of BBB
      disrupting genes in juveniles compared with adults. These differences were
      concomitant with significant changes in miRNA-21-5p and miR-148a levels.
      Accompanying these findings was robust GFAP immunoreactivity, which was not
      resolved by day 35. Importantly, pharmacological inhibition of EC-specific Tie2
      signaling abolished the juvenile protective effects. These findings shed new
      mechanistic light on the divergent effects that age plays on acute TBI outcome
      that are both spatial and temporal dependent.SIGNIFICANCE STATEMENT Although a
      clear "window of susceptibility" exists in the developing brain that could deter
      typical developmental trajectories if exposed to trauma, a number of preclinical
      models have demonstrated evidence of early recovery in younger patients. Our
      findings further demonstrate acute neuroprotection and improved restoration of
      cerebral blood flow in juvenile mice subjected to cortical contusion injury
      compared with adults. We also demonstrate a novel role for endothelial cell
      specific Tie2 signaling in this age-related response, which is known to promote
      barrier stability, is heightened in the injured juvenile vasculature, and may be
      exploited for therapeutic interventions across the age spectrum following
      traumatic brain injury.

PMID- 30242054
TI  - Feature-Specific Awake Reactivation in Human V1 after Visual Training.
AB  - Brain activity patterns exhibited during task performance have been shown to
      spontaneously reemerge in the following restful awake state. Such "awake
      reactivation" has been observed across higher-order cortex for complex images or
      associations. However, it is still unclear whether the reactivation extends to
      primary sensory areas that encode simple stimulus features. To address this
      question, we trained human subjects from both sexes on a particular visual
      feature (Gabor orientation) and tested whether this feature will be reactivated
      immediately after training. We found robust reactivation in human V1 that lasted
      for at least 8 min after training offset. This effect was not present in higher
      retinotopic areas, such as V2, V3, V3A, or V4v. Further analyses suggested that
      the amount of awake reactivation was related to the amount of performance
      improvement on the visual task. These results demonstrate that awake reactivation
      extends beyond higher-order areas and also occurs in early sensory
      cortex.SIGNIFICANCE STATEMENT How do we acquire new memories and skills? New
      information is known to be consolidated during offline periods of rest. Recent
      studies suggest that a critical process during this period of consolidation is
      the spontaneous reactivation of previously experienced patterns of neural
      activity. However, research in humans has mostly examined such reactivation
      processes in higher-order cortex. Here we show that awake reactivation occurs
      even in the primary visual cortex V1 and that this reactivation is related to the
      amount of behavioral learning. These results pinpoint awake reactivation as a
      process that likely occurs across the entire human brain and could play an
      integral role in memory consolidation.

PMID- 30242055
TI  - Epigenetic Silencing of THY1 Tracks the Acquisition of the Notch1-EGFR Signaling
      in a Xenograft Model of CD44+/CD24low/CD90+ Myoepithelial Cells.
AB  - The surface glycoprotein THY is a marker of myoepithelial precursor cells, which
      are basal cells with epithelial-mesenchymal intermediate phenotype originating
      from the ectoderm. Myoepithelial precursor cells are lost during progression from
      in situ to invasive carcinoma. To define the functional role of Thy1-positive
      cells within the myoepithelial population, we tracked Thy1 expression in human
      breast cancer samples, isolated THY1-positive myoepithelial progenitor cells
      (CD44+/CD24low/CD90+), and established long-term cultures (parental cells).
      Parental cells were used to generate a xenograft model to examine Thy1 expression
      during tumor formation. Post-transplantation cell cultures lost THY1 expression
      through methylation at the THY1 locus and this is associated with an increase in
      EGFR and NOTCH1 transcript levels. Thy1-low cells are sensitive to the EGFR/HER2
      dual inhibitor lapatinib. High THY1 expression is associated with poorer relapse
      free survival in patients with breast cancer. THY1 methylation may track the
      shift of bipotent progenitors into differentiated cells. Thy1 is a good candidate
      biomarker in basal-like breast cancer.Implications: Our findings provide evidence
      that THY1 expression is lost in xenografts due to promoter methylation. Thy1-low
      cells with increased EGFR and Notch1 expression are responsive to target therapy.
      Because DNA methylation is often altered in early cancer development, candidate
      methylation markers may be exploited as biomarkers for basal-like breast cancer.
      Mol Cancer Res; 1-14. (c)2018 AACR.

PMID- 30242057
TI  - Overexpression of the nucleocapsid protein of Middle East respiratory syndrome
      coronavirus up-regulates CXCL10.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory
      diseases in humans and has a high mortality rate. During infection, MERS-CoV
      regulates several host cellular processes including antiviral response genes. In
      order to determine if the nucleocapsid protein of MERS-CoV (MERS-N) plays a role
      in viral-host interactions, a murine monoclonal antibody was generated so as to
      allow detection of the protein in infected cells as well as in overexpression
      system. Then, MERS-N was stably overexpressed in A549 cells, and a PCR array
      containing 84 genes was used to screen for genes transcriptionally regulated by
      it. Several up-regulated antiviral genes, namely TNF, IL6, IL8, and CXCL10, were
      selected for independent validation in transiently transfected 293FT cells. Out
      of these, the overexpression of MERS-N was found to up-regulate CXCL10 at both
      transcriptional and translational levels. Interestingly, CXCL10 has been reported
      to be up-regulated in MERS-CoV infected airway epithelial cells and lung
      fibroblast cells, as well as monocyte-derived macrophages and dendritic cells.
      High secretions and persistent increase of CXCL10 in MERS-CoV patients have been
      also associated with severity of disease. To our knowledge, this is the first
      report showing that the MERS-N protein is one of the contributing factors for
      CXCL10 up-regulation during infection. In addition, our results showed that a
      fragment consisting of residues 196-413 in MERS-N is sufficient to up-regulate
      CXCL10, while the N-terminal domain and serine-arginine (SR)-rich motif of MERS-N
      do not play a role in this up-regulation.

PMID- 30242056
TI  - Associations between circulating IgG antibodies to Apolipoprotein B100-derived
      peptide antigens and acute coronary syndrome in a Chinese Han population.
AB  - Objectives: Acute coronary syndrome (ACS) is the major cause of mortality
      worldwide and caused mainly by atherosclerosis of coronary arteries.
      Apolipoprotein B100 (ApoB100) is a major component of low-density lipoprotein
      (LDL) and its oxidation can trigger inflammation in vascular endothelial cells
      leading to atherosclerosis. The association between antibodies to ApoB100-derived
      antigens and atherosclerotic diseases has been studied in recent years, but the
      findings appear to be controversial. The present study developed an ELISA in
      house with ApoB100-derived peptide antigens to circulating anti-ApoB100 IgG
      antibodies in patients with ACS. Methods: Fifteen ApoB100-derived peptide
      antigens (Ag1-Ag15) were designed to develop an in-house ELISA for the detection
      of circulating anti-ApoB100 IgG levels in 350 patients with ACS and 201 control
      subjects amongst a Chinese population. Binary logistic regression was applied to
      examine the differences in anti-ApoB IgG levels between the patient group and the
      control group with adjustment for a number of confounding factors; the
      correlation between anti-ApoB100 IgG levels and clinical characteristics was also
      tested. Results: Patients with ACS had significantly higher levels of plasma IgG
      for Ag1 (adjusted P<0.001) and Ag10 antigens (adjusted P<0.001). There was no
      significant increase in the levels of IgG to the other 13 antigens in these ACS
      patients. In the control group, anti-Ag10 IgG levels were positively correlated
      with age, high-density lipoprotein (HDL), and ApoA levels (P<=0.001 for all) and
      negatively correlated with blood triglyceride (TG) (P=0.008); in the patient
      group, anti-Ag10 IgG levels were positively correlated with LDL (P=0.003), and
      negatively correlated with ApoA (P=0.048) and systolic blood pressure (SBP)
      (P=0.036). The area under ROC (receiver operator characteristic) curve (AUC) was
      0.612 (95% confidence interval (CI): 0.560-0.664; P<0.001) in anti-Ag1 IgG assay
      and 0.621 (95% CI: 0.569-0.672; P<0.001) in anti-Ag10 IgG assay. Conclusion:
      Circulating IgG for ApoB100-derived peptide antigens may be a useful biomarker of
      ACS, although anti-ApoB IgG levels were not associated with the coronary artery
      plaque burden characterized by the coronary Gensini score.

PMID- 30242058
TI  - Bakuchiol protects against pathological cardiac hypertrophy by blocking NF-kappaB
      signaling pathway.
AB  - Bakuchiol (Bak), a monoterpene phenol isolated from the seeds of Psoralea
      corylifolia, has been widely used to treat a large variety of diseases in both
      Indian and Chinese folkloric medicine. However, the effects of Bak on cardiac
      hypertrophy remain unclear. Therefore, the present study was designed to
      determine whether Bak could alleviate cardiac hypertrophy. Mice were subjected to
      aortic banding (AB) to induce cardiac hypertrophy model. Bak of 1 ml/100 g body
      weight was given by oral gavage once a day from 1 to 8 weeks after surgery. Our
      data demonstrated for the first time that Bak could attenuate pressure overload
      induced cardiac hypertrophy and could attenuate fibrosis and the inflammatory
      response induced by AB. The results further revealed that the effect of Bak on
      cardiac hypertrophy was mediated by blocking the activation of the NF-kappaB
      signaling pathway. In vitro studies performed in neonatal rat cardiomyocytes
      further proved that the protective effect of Bak on cardiac hypertrophy is
      largely dependent on the NF-kappaB pathway. Based on our results, Bak shows
      profound potential for its application in the treatment of pathological cardiac
      hypertrophy, and we believe that Bak may be a promising therapeutic candidate to
      treat cardiac hypertrophy and heart failure.

PMID- 30242059
TI  - Structural and functional characterisation of the entry point to pyocyanin
      biosynthesis in Pseudomonas aeruginosa defines a new 3-deoxy-d-arabino
      heptulosonate 7-phosphate synthase subclass.
AB  - In Pseudomonas aeruginosa (Pae), the shikimate pathway end product, chorismate,
      serves as the last common precursor for the biosynthesis of both primary aromatic
      metabolites, including phenylalanine, tyrosine and tryptophan, and secondary
      aromatic metabolites, including phenazine-1-carboxylic acid (PCA) and pyocyanin
      (PYO). The enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS)
      catalyses the first committed step of the shikimate pathway, en route to
      chorismate. P. aeruginosa expresses multiple, distinct DAH7PSs that are
      associated with either primary or secondary aromatic compound biosynthesis. Here
      we report the structure of a type II DAH7PS, encoded by phzC as part of the
      duplicated phenazine biosynthetic cluster, from P. aeruginosa (PAO1) revealing
      for the first time the structure of a type II DAH7PS involved in secondary
      metabolism. The omission of the structural elements alpha2a and alpha2b, relative
      to other characterised type II DAH7PSs, leads to the formation of an alternative,
      dimeric, solution-state structure for this type II DAH7PS with an oligomeric
      interface that has not previously been characterised and that does not facilitate
      the formation of aromatic amino acid allosteric binding sites. The sequence
      similarity and, in particular, the common N-terminal extension suggest a common
      origin for the type II DAH7PSs from P. aeruginosa. The results described in the
      present study support an expanded classification of the type II DAH7PSs as type
      IIA and type IIB based on sequence characteristics, structure and function of the
      resultant proteins, and on defined physiological roles within primary or
      secondary metabolism.

PMID- 30242060
TI  - How well can poor child health and development be predicted by data collected in
      early childhood?
AB  - BACKGROUND: Identifying children at risk of poor developmental outcomes remains a
      challenge, but is important for better targeting children who may benefit from
      additional support. We explored whether data routinely collected in early life
      predict which children will have language disability, overweight/obesity or
      behavioural problems in later childhood. METHODS: We used data on 10 262 children
      from the UK Millennium Cohort Study (MCS) collected at 9 months, 3, and 11 years
      old. Outcomes assessed at age 11 years were language disability,
      overweight/obesity and socioemotional behavioural problems. We compared the
      discriminatory capacity of three models: (1) using data currently routinely
      collected around the time of birth; (2) Model 1 with additional data routinely
      collected at 3 years; (3) a statistically selected model developed using a larger
      set of early year's risk factors for later child health outcomes, available in
      the MCS-but not all routinely collected. RESULTS: At age 11, 6.7% of children had
      language disability, 26.9% overweight/obesity and 8.2% socioemotional behavioural
      problems. Model discrimination for language disability was moderate in all three
      models (area under the curve receiver-operator characteristic 0.71, 0.74 and
      0.76, respectively). For overweight/obesity, it was poor in model 1 (0.66) and
      moderate for model 2 (0.73) and model 3 (0.73). Socioemotional behavioural
      problems were also identified with moderate discrimination in all models (0.71;
      0.77; 0.79, respectively). CONCLUSION: Language disability, socioemotional
      behavioural problems and overweight/obesity in UK children aged 11 years are
      common and can be predicted with moderate discrimination using data routinely
      collected in the first 3 years of life.

PMID- 30242061
TI  - Update on corneal neurotisation.
AB  - Corneal neurotisation describes surgical restoration of nerve growth into the
      cornea to restore corneal sensation and trophic function. It represents an
      exciting and effective emerging treatment for neurotrophic keratopathy.
      Techniques described to date involve either direct nerve transfer or an
      interpositional nerve graft coapted to a healthy donor nerve. We review the
      experience to date with particular emphasis on a detailed review of techniques,
      outcomes and current thoughts.

PMID- 30242062
TI  - Changes in intraocular pressure after intravitreal fluocinolone acetonide
      (ILUVIEN): real-world experience in three European countries.
AB  - AIMS: The ILUVIEN Registry Safety Study is an ongoing, multicentre, open-label,
      observational study collecting real-world data on the safety and effectiveness of
      the 0.2 ug/day fluocinolone acetonide (FAc) implant in patients treated according
      to the European label requirements. METHODS: Patients included in this analysis
      were treated for the licensed indication of chronic diabetic macular oedema
      (cDMO; that is, DMO that persists or recurs despite treatment). Data presented in
      the current analysis were collected from patient records up to 6 March 2017.
      Visual acuity (VA) data, including mean change in VA over time and at last
      observation, intraocular pressure (IOP) over the course of the study, IOP events,
      use of IOP-lowering therapy and cup:disc ratio were analysed. Information on
      additional DMO treatments post-FAc implant was also captured. RESULTS: Five
      hundred and sixty-three patients (593 eyes) were enrolled on the study. Mean IOP
      for the overall population remained within the normal range throughout follow-up
      and 76.7% of patients did not require IOP-lowering therapy following treatment
      with the FAc implant. Sixty-nine per cent of eyes did not require additional DMO
      treatments. Mean VA in the overall population increased from 51.9 letters at
      baseline to 55.6 letters at month 12, with a significant increase of 2.9 letters
      at last observation. Patients with short-term cDMO experienced greater VA gains
      than those with long-term cDMO. CONCLUSIONS: The results of this analysis are
      comparable with those of other studies, including the Fluocinolone Acetate for
      Macular Edema study. The study reinforces the good safety and effectiveness
      profile of FAc, and demonstrates the benefit of early FAc treatment.

PMID- 30242064
TI  - Role of ATP during the initiation of microvascularization: acceleration of an
      autocrine sensing mechanism facilitating chemotaxis by inorganic polyphosphate.
AB  - The in vitro tube formation assay with human umbilical vein endothelial cells
      (HUVEC) was applied to identify the extra- and intracellular sources of metabolic
      energy/ATP required for cell migration during the initial stage of
      microvascularization. Extracellularly, the physiological energy-rich polymer,
      inorganic polyphosphate (polyP), applied as biomimetic amorphous calcium polyP
      microparticles (Ca-polyP-MP), is functioning as a substrate for ATP generation
      most likely via the combined action of the alkaline phosphatase (ALP) and the
      adenylate kinase (AK). The linear Ca-polyP-MP with a size of 40 phosphate units,
      close to the polyP in the acidocalcisomes in the blood platelets, were found to
      increase endothelial cell tube formation, as well as the intracellular ATP
      levels. Depletion of extracellular ATP with apyrase suppressed tube formation
      during the initial incubation period. Inhibition experiments revealed that
      inhibitors (levamisole and Ap5A) of the enzymes involved in extracellular ATP
      generation strongly reduce the Ca-polyP-MP-induced tube formation. The
      stimulatory effect of Ca-polyP-MP was also diminished by the glycolysis inhibitor
      oxamate and trifluoperazine which blocks endocytosis, as well as by MRS2211, an
      antagonist of the P2Y13 receptor. Oligomycin, an inhibitor of the mitochondrial
      F0F1-ATP synthase, displayed no effect at lower concentrations on tube formation.
      Electron microscopic data revealed that after cellular uptake, the Ca-polyP-MP
      accumulate close to the cell membrane. We conclude that in HUVEC exposed to
      polyP, ATP is formed extracellularly via the coupled ALP-AK reaction, and
      intracellularly during glycolysis. The results suggest an autocrine signaling
      pathway of ATP with polyP as an extracellular store of metabolic energy for
      endothelial cell migration during the initial vascularization process.

PMID- 30242063
TI  - Mouse adult hematopoietic stem cells actively synthesize ribosomal RNA.
AB  - The contribution of basal cellular processes to the regulation of tissue
      homeostasis has just started to be appreciated. However, our knowledge of the
      modulation of ribosome biogenesis activity in situ within specific lineages
      remains very limited. This is largely due to the lack of assays that enable
      quantitation of ribosome biogenesis in small numbers of cells in vivo. We used a
      technique, named Flow-FISH, combining cell surface antibody staining and flow
      cytometry with intracellular ribosomal RNA (rRNA) FISH, to measure the levels of
      pre-rRNAs of hematopoietic cells in vivo. Here, we show that Flow-FISH reports
      and quantifies ribosome biogenesis activity in hematopoietic cell populations,
      thereby providing original data on this fundamental process notably in rare
      populations such as hematopoietic stem and progenitor cells. We unravel
      variations in pre-rRNA levels between different hematopoietic progenitor
      compartments and during erythroid differentiation. In particular, our data
      indicate that, contrary to what may be anticipated from their quiescent state,
      hematopoietic stem cells have significant ribosome biogenesis activity. Moreover,
      variations in pre-rRNA levels do not correlate with proliferation rates,
      suggesting that cell type-specific mechanisms might regulate ribosome biogenesis
      in hematopoietic stem cells and progenitors. Our study contributes to a better
      understanding of the cellular physiology of the hematopoietic system in vivo in
      unperturbed situations.

PMID- 30242065
TI  - N-terminal acetylation and methylation differentially affect the function of
      MYL9.
AB  - Deciphering the histone code has illustrated that acetylation or methylation on
      the same residue can have analogous or opposing roles. However, little is known
      about the interplay between these post-translational modifications (PTMs) on the
      same nonhistone residues. We have recently discovered that N-terminal
      acetyltransferases (NATs) and N-terminal methyltransferases (NRMTs) can have
      overlapping substrates and identified myosin regulatory light chain 9 (MYL9) as
      the first confirmed protein to occur in either alpha-amino-methylated (Nalpha
      methyl) or alpha-amino-acetylated (Nalpha-acetyl) states in vivo Here we aim to
      determine if these PTMs function similarly or create different MYL9 proteoforms
      with distinct roles. We use enzymatic assays to directly verify MYL9 is a
      substrate of both NRMT1 and NatA and generate mutants of MYL9 that are exclusive
      for Nalpha-acetylation or Nalpha-methylation. We then employ eukaryotic cell
      models to probe the regulatory functions of these Nalpha-PTMs on MYL9. Our
      results show that, contrary to prevailing dogma, neither of these modifications
      regulate the stability of MYL9. Rather, exclusive Nalpha-acetylation promotes
      cytoplasmic roles of MYL9, while exclusive Nalpha-methylation promotes the
      nuclear role of MYL9 as a transcription factor. The increased cytoplasmic
      activity of Nalpha-acetylated MYL9 corresponds with increased phosphorylation at
      serine 19, a key MYL9 activating PTM. Increased nuclear activity of Nalpha
      methylated MYL9 corresponds with increased DNA binding. Nalpha-methylation also
      results in a decrease of interactions between the N-terminus of MYL9 and a host
      of cytoskeletal proteins. These results confirm that Nalpha-acetylation and
      Nalpha-methylation differentially affect MYL9 function by creating distinct
      proteoforms with different internal PTM patterns and binding properties.

PMID- 30242066
TI  - Trabectedin plus Olaparib Has Activity in Patients with Soft-Tissue Sarcoma.
AB  - Trabectedin had manageable toxicity in combination with olaparib in a phase Ib
      trial.

PMID- 30242067
TI  - The Tumor Microenvironment Drives Liver Cancer Lineage Commitment.
AB  - The hepatic microenvironment epigenetically directs lineage commitment to promote
      ICC or HCC liver tumors.

PMID- 30242068
TI  - Camrelizumab Has Activity in Patients with Nasopharyngeal Carcinoma.
AB  - The PD-1 antibody camrelizumab was well tolerated in patients with nasopharyngeal
      carcinoma.

PMID- 30242069
TI  - (R)-2HG Inhibits the BCAT Transaminase in IDH-Mutant Glioma.
AB  - BCAT inactivation renders IDH-mutant cells dependent on glutaminase for glutamate
      and glutathione synthesis.

PMID- 30242070
TI  - MLL1-Induced Oncogenic Reprogramming Drives EZH2 Inhibitor Resistance.
AB  - Tumor-intrinsic MLL1 drives transcriptional reprogramming in response to EZH2
      inhibition.

PMID- 30242071
TI  - Alcohol is blamed for one in 20 deaths as reduced consumption remains elusive.

PMID- 30242072
TI  - IL-33 Upregulates Cysteinyl Leukotriene Receptor Type 1 Expression in Human
      Peripheral Blood CD4+ T Lymphocytes.
AB  - IL-33 and cysteinyl leukotrienes (cysLTs) are key components of asthma
      pathogenesis, and both contribute to the initiation and maintenance of the type 2
      inflammatory environment. However, little is known about the potential
      interactions between the two mediators. In this work, we aimed at studying the
      regulation of expression of the cysLT receptors CysLT1 and CysLT2 by IL-33 in
      human PBLs. Our results show that the IL-33/ST2L axis increases CysLT1 but not
      CysLT2 expression in a concentration- and time-dependent manner in PBLs. IL-33
      induced CysLT1 upregulation was observed at the protein but not at the mRNA level
      and was accompanied by an increase in LTD4-induced calcium mobilization and
      migration of CD4+ T lymphocytes. We also show that purified naive CD4+ T
      lymphocytes expressed ST2L and responded to IL-33 in the absence of Ag or TCR
      stimulation, suggesting a mechanism independent of Ag presentation. These results
      contribute to expanding our knowledge in the field of IL-33 by proposing a new
      mode of action of the cytokine on T cells and by extending its role to the
      regulation of naive T cell trafficking, therefore reinforcing its interest as a
      potential therapeutic target for the treatment of asthma.

PMID- 30242074
TI  - Obstetrician is cleared of initiating affair with private patient.

PMID- 30242075
TI  - Incidence of Congenital Hypothyroidism Over 37 Years in Ireland.
AB  - BACKGROUND AND OBJECTIVES: Congenital hypothyroidism (CHT) is one of the most
      common preventable causes of learning disability. Newborn screening with whole
      blood thyroid-stimulating hormone measurements was introduced in the Republic of
      Ireland in 1979 and is coordinated from a single center with an unchanged
      protocol since its inception. Our objective in this study was to describe the
      incidence of CHT in the Republic of Ireland over the past 37 years in the context
      of a complete national population and an unchanged screening protocol. METHODS:
      The newborn screening records of all individuals who were diagnosed with CHT
      between 1979 and 2016 were reviewed. Infants with positive screening results had
      a whole-blood thyroid-stimulating hormone value of >=15 mU/L at 72 to 120 hours
      of life; values of 8 to 15 mU/L required a repeat whole-blood screening test.
      RESULTS: Of 2 361 174 infants who were screened between July 1979 and December
      2016, 1063 (662 girls) were diagnosed with CHT (incidence: 0.45 cases per 1000
      live births). The number of detected cases increased from 0.27 cases per 1000
      live births treated between 1979 and 1991 to 0.41 cases per 1000 live births
      treated between 1992 and 2004 to 0.65 cases per 1000 live births treated between
      2005 and 2016. The increase in detected cases of CHT was predominantly in the
      normal or hyperplastic gland category. CONCLUSIONS: The incidence of CHT has
      increased significantly in the Republic of Ireland over the past 37 years despite
      a consistent screening cutoff. The increased rate was not explained by an
      increased survival rate of preterm infants or a changing population
      heterogeneity.

PMID- 30242073
TI  - Stabilization of Foxp3 by Targeting JAK2 Enhances Efficacy of CD8 Induced
      Regulatory T Cells in the Prevention of Graft-versus-Host Disease.
AB  - CD8+ induced regulatory T cells (iTregs) have been identified to suppress
      alloreactive immune responses and expressed regulatory T cell (Treg) ontological
      markers as similar as CD4+ iTregs. However, adoptive transfer of CD8+ iTreg-based
      therapy is hampered by the instability of Treg specific-transcription factor,
      Foxp3. As CD8+ iTregs were previously demonstrated to possess superior tumor
      killing ability to CD4+ iTregs, adoptive transfer of stabilized CD8+ iTregs would
      be a potential therapy to prevent tumor relapse during graft-versus-leukemia
      disease (GVHD) treatment. In the current study, we generated alloantigen reactive
      CD8+ iTregs from JAK2-/- T cells and adoptively transferred them to MHC
      mismatched and haploidentical murine models of allogeneic bone marrow
      transplantation. JAK2-/- CD8+ iTregs not only attenuated GVHD but also preserved
      graft-versus-leukemia effect. Mechanistic analysis revealed that JAK2-/- CD8+
      iTregs upregulated natural Treg marker (neuropilin-1), and augmented DNA
      demethylation of CNS2 region within Foxp3 gene. These properties licensed JAK2-/-
      CD8+ iTregs to retain high Foxp3 expression resulting in less conversion to type
      1 CTLs; as a result, JAK2-/- CD8+ iTregs were able to maintain their suppressive
      and cytolytic function. Thus, our findings provide a strong rationale and means
      to stabilize CD8+ iTregs by targeting JAK2, and the stabilized CD8+ iTregs
      exhibit therapeutic potential for alleviating GVHD and preserving the graft
      versus-leukemia effect.

PMID- 30242076
TI  - Congenital Hypothyroidism: Inside Ireland's Incline.

PMID- 30242077
TI  - Conscientious objection to referrals.
AB  - Christopher Cowley1 has recently put forward three arguments against the legal
      accommodation of a general practitioner's conscientious objection (CO) to
      abortion referrals.i He claims that the adoption of these arguments does not
      undermine a more general right to CO to involvement in abortion. I argue that
      Cowley is seriously mistaken. His three arguments, especially the second and
      third, proceed on a path directed towards the outright rejection of a right to CO
      in healthcare contexts. A common problem with Cowley's three arguments is that
      they overlook the peremptory significance for CO analysis of both the internal,
      deliberating perspective of those with a CO and the good of moral integrity. This
      paper supports the view that either there are strong prima facie grounds for
      holding that a right to CO extends in principle to the issue of referrals or the
      claim of a general right to CO is easily assailable.

PMID- 30242078
TI  - The best interest standard and children: clarifying a concept and responding to
      its critics.
AB  - This work clarifies the role of the best interest standard (BIS) as ethical
      principle in the medical care of children. It relates the BIS to the ethical
      framework of medical practice. The BIS is shown to be a general principle in
      medical ethics, providing grounding to prima facie obligations. The foundational
      BIS of Kopelman and Buchanan and Brock are reviewed and shown to be in agreement
      with the BIS here defended. Critics describe the BIS as being too demanding,
      narrow, opaque, not taking the family into account and not suitable as limiting
      principle. This work responds to these criticisms, showing that they do not stand
      up to scrutiny. They either do not apply to the BIS, only apply to misuses of the
      BIS or criticise a BIS that is not seriously defended in the literature.

PMID- 30242079
TI  - Medical Assistance in Dying at a paediatric hospital.
AB  - This article explores the ethical challenges of providing Medical Assistance in
      Dying (MAID) in a paediatric setting. More specifically, we focus on the
      theoretical questions that came to light when we were asked to develop a policy
      for responding to MAID requests at our tertiary paediatric institution. We
      illuminate a central point of conceptual confusion about the nature of MAID that
      emerges at the level of practice, and explore the various entailments for
      clinicians and patients that would flow from different understandings. Finally,
      we consider the ethical challenges of building policy on what is still an
      extremely controversial social practice. While MAID is currently available to
      capable patients in Canada who are 18 years or older-a small but important
      subsection of the population our hospital serves-we write our policy with an eye
      to the near future when capable young people may gain access to MAID. We propose
      that an opportunity exists for MAID-providing institutions to reduce social
      stigma surrounding this practice, but not without potentially serious
      consequences for practitioners and institutions themselves. Thus, this paper is
      intended as a road map through the still-emerging legal and ethical landscape of
      paediatric MAID. We offer a view of the roads taken and considered along the way,
      and our justifications for travelling the paths we chose. By providing a record
      of our in-progress thinking, we hope to stimulate wider discussion about the
      issues and questions encountered in this work.

PMID- 30242080
TI  - Enhancing FcgammaR-mediated antibody effector function during persistent viral
      infection.
AB  - Persistent viral infections can interfere with FcgammaR-mediated antibody
      effector functions by excessive immune complex (IC) formation, resulting in
      resistance to therapeutic FcgammaR-dependent antibodies. We and others have
      previously demonstrated that mice persistently infected with lymphocytic
      choriomeningitis virus (LCMV) are resistant to a wide range of depleting
      antibodies due to excessive IC formation. Here, we dissect the mechanisms by
      which two depleting antibodies overcome the obstacle of endogenous ICs and
      achieve efficient target cell depletion in persistently infected mice. Efficient
      antibody-mediated depletion during persistent LCMV infection required increased
      levels of antibody bound to target cells or use of afucosylated antibodies with
      increased affinity for FcgammaRs. Antibodies targeting the highly expressed CD90
      antigen or overexpressed human CD20 efficiently depleted their target cells in
      naive and persistently infected mice, whereas antibodies directed against less
      abundant antigens failed to deplete their target cells during persistent LCMV
      infection. In addition, we demonstrate the superior activity of afucosylated
      antibodies in the presence of endogenous ICs. We generated afucosylated
      antibodies directed against CD4 and CD8alpha, which, in contrast to their
      parental fucosylated versions, efficiently depleted their respective target cells
      in persistently infected mice. Efficient antibody-mediated depletion can thus be
      achieved if therapeutic antibodies can outcompete endogenous ICs for access to
      FcgammaRs either by targeting highly expressed antigens or by increased affinity
      for FcgammaRs. Our findings have implications for the optimization of therapeutic
      antibodies and provide strategies to allow efficient FcgammaR engagement in the
      presence of competing endogenous ICs in persistent viral infections, autoimmune
      diseases, and cancer.

PMID- 30242081
TI  - L580m boost to general practice isn't enough, say GP leaders.

PMID- 30242082
TI  - Eimeria species in cattle with diarrhoea in the Republic of Korea regarding age,
      season and nature of diarrhoea.
AB  - This study evaluated the prevalence of Eimeria species, particularly E bovis, E
      zuernii and E auburnensis that are pathogenic to cattle, in faecal samples
      collected from cattle with diarrhoea reared in the Republic of Korea by using
      microscopy and PCR. In addition, the prevalence of Eimeria species was analysed
      according to age, type of cattle, region, season and nature of diarrhoea.
      Overall, Eimeria species were identified in 279 of the 1261 (22.1 per cent)
      faecal samples through microscopy, and statistical analysis revealed a lower
      prevalence in calves aged than three weeks or less and higher prevalence in
      cattle with haemorrhagic diarrhoea. Of the 279 microscopy-positive samples, E
      bovis, E zuernii and E auburnensis were identified in 100 (7.9 per cent), 83 (6.6
      per cent) and 27 (2.1 per cent) faecal samples, respectively, by using PCR. To
      the authors' knowledge, this study is the first to apply PCR for epizootiology of
      bovine coccidiosis.

PMID- 30242083
TI  - Reliability of equine visual lameness classification as a function of expertise,
      lameness severity and rater confidence.
AB  - Visual equine lameness assessment is often unreliable, yet the full understanding
      of this issue is missing. Here, we investigate visual lameness assessment using
      near-realistic, three-dimensional horse animations presenting with 0-60 per cent
      movement asymmetry. Animations were scored at an equine veterinary seminar by
      attendees with various expertise levels. Results showed that years of experience
      and exposure to a low, medium or high case load had no significant effect on
      correct assessment of lame (P>0.149) or sound horses (P>=0.412), with the
      exception of a significant effect of case load exposure on forelimb lameness
      assessment at 60 per cent asymmetry (P=0.014). The correct classification of
      sound horses as sound was significantly (P<0.001) higher for forelimb (average 72
      per cent correct) than for hindlimb lameness assessment (average 28 per cent
      correct): participants often saw hindlimb lameness where there was none. For
      subtle lameness, errors often resulted from not noticing forelimb lameness and
      from classifying the incorrect limb as lame for hindlimb lameness. Diagnostic
      accuracy was at or below chance level for some metrics. Rater confidence was not
      associated with performance. Visual gait assessment may overall be unlikely to
      reliably differentiate between sound and mildly lame horses irrespective of an
      assessor's background.

PMID- 30242084
TI  - Brexit and health in Ireland: Doctors' concerns about crossborder care.

PMID- 30242085
TI  - miR-125a and miR-34a expression predicts Richter syndrome in chronic lymphocytic
      leukemia patients.
AB  - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. It is
      characterized by the accumulation of CD19+/CD5+ lymphocytes and can have variable
      outcomes. Richter syndrome (RS) is a lethal complication in CLL patients that
      results in aggressive B-cell lymphomas, and there are no tests to predict its
      occurrence. Because alterations in microRNA expression can predict the
      development and progression of several cancers, we investigated whether
      dysregulation of specific microRNAs can predict RS in CLL patients. Thus, we
      compared microRNA expression levels in samples from 49 CLL patients who later
      developed RS with samples from 59 CLL patients who did not. We found that high
      expression of miR-125a-5p or low expression of miR -34a-5p can predict ~50% of RS
      with a false positive rate of ~9%. We found that CLL patients predicted to
      develop RS show either an increase of miR-125a-5p expression (~20-fold) or a
      decrease of miR-34a-5p expression (~21-fold) compared with CLL patients that are
      not predicted to develop RS. Thus, miR-125a-5p and miR-34a-5p can be valuable
      predictor markers of RS and have the potential to provide physicians with
      information that can indicate the best therapeutic strategy for CLL patients.

PMID- 30242086
TI  - Beyond NEOD001 for systemic light-chain amyloidosis.

PMID- 30242087
TI  - Mutational landscape of myelodysplastic/myeloproliferative neoplasm
      unclassifiable.

PMID- 30242089
TI  - Unravelling of the paroxysmal dyskinesias.
AB  - Paroxysmal dyskinesias (PxD) refer to a rare group of clinically and genetically
      heterogeneous disorders presenting with recurrent attacks of abnormal movements,
      typically dystonia, chorea or a combination thereof, without loss of
      consciousness. Classically, PxD have been categorised according to their triggers
      and duration of the attacks, but increasing evidence suggests that there is a
      certain degree of clinical and genetic overlap and challenges the concept that
      one phenotype is attributable to one single aetiology. Here we review the
      increasing spectrum of genetic conditions, as well as of other non-genetic
      disorders, that might present with PxD, provide criteria for case definition and
      propose a diagnostic workup to reach a definitive diagnosis, on which treatment
      is heavily dependent.

PMID- 30242088
TI  - Clinical features and prognosis of amyotrophic lateral sclerosis in Africa: the
      TROPALS study.
AB  - OBJECTIVE: We describe and compare the sociodemographic and clinical features,
      treatments, and prognoses and survival times of patients with amyotrophic lateral
      sclerosis (ALS) in Africa. METHODOLOGY: We conducted a multicentre, hospital
      based cohort study in Africa. Patients with ALS diagnosed in the neurology
      departments of participating hospitals from 2005 to 2017 were included. Subgroup
      analysis was performed by subcontinent. Survival analyses were conducted using
      the Cox proportional hazards model. RESULTS: Nine centres from eight African
      countries participated. A total of 185 patients with ALS were included: 114 from
      Northern Africa, 41 from Western Africa and 30 from Southern Africa. A male
      predominance (male to female ratio 2.9) was evident. The median age at onset was
      53.0 years (IQR 44.5-64.0 years). The onset was bulbar in 22.7%. Only 47 patients
      (26.3%) received riluzole, mainly in Northern and Western Africa. The median
      survival from the time of diagnosis was 14.0 months (95% CI 10.7 to 17.2 months).
      The median survival was longer in Northern Africa (19.0 months, 95% CI 10.8 to
      27.2 months) than in Western (4.0 months, 95% CI 0.8 to 7.1 months) and Southern
      (11.0 months, 95% CI 5.6 to 16.4 months) Africa (Breslow test, p<0.0001). Both
      subcontinental location and riluzole treatment independently affected survival.
      CONCLUSION: More African patients with ALS were male and younger and exhibited a
      lower proportion of bulbar onset compared with patients with ALS from Western
      nations. Survival was consistent with that in Western registers but far shorter
      than what would be expected for young patients with ALS. The research improves
      our understanding of the disease in Africa.

PMID- 30242091
TI  - Targeted Delivery of Cytotoxic NAMPT Inhibitors Using Antibody-Drug Conjugates.
AB  - Antibody-drug conjugates (ADCs) are a therapeutic modality that enables the
      targeted delivery of cytotoxic drugs to cancer cells. Identification of active
      payloads with unique mechanisms of action is a key aim of research efforts in the
      field. Herein, we report the development of inhibitors of nicotinamide
      phosphoribosyltransferase (NAMPT) as a novel payload for ADC technology. NAMPT is
      a component of a salvage biosynthetic pathway for NAD, and inhibition of this
      enzyme results in disruption of primary cellular metabolism leading to cell
      death. Through derivatization of the prototypical NAMPT inhibitor FK-866, we
      identified potent analogues with chemical functionality that enables the
      synthesis of hydrophilic enzyme-cleavable drug linkers. The resulting ADCs
      displayed NAD depletion in both cell-based assays and tumor xenografts. Antitumor
      efficacy is demonstrated in five mouse xenograft models using ADCs directed to
      indication-specific antigens. In rat toxicology models, a nonbinding control ADC
      was tolerated at >10-fold the typical efficacious dose used in xenografts.
      Moderate, reversible hematologic effects were observed with ADCs in rats, but
      there was no evidence for the retinal and cardiac toxicities reported for small
      molecule inhibitors. These findings introduce NAMPT inhibitors as active and well
      tolerated payloads for ADCs with promise to improve the therapeutic window of
      NAMPT inhibition and enable application in clinical settings.

PMID- 30242090
TI  - Assessing the long-term effectiveness of interferon-beta and glatiramer acetate
      in multiple sclerosis: final 10-year results from the UK multiple sclerosis risk
      sharing scheme.
AB  - BACKGROUND: Because multiple sclerosis (MS) is a chronic disease causing
      disability over decades, it is crucial to know if the short-term effects of
      disease-modifying therapies reported in randomised controlled trials reduce long
      term disability. This 10-year prospective observational study of disability
      outcomes (Expanded Disability Status Scale (EDSS) and utility) was set up, in
      conjunction with a risk-sharing agreement between payers and producers, to
      investigate this issue. METHODS: The outcomes of the UK treated patients were
      compared with a modelled untreated control based on the British Columbia MS data
      set to assess the long-term effectiveness of these treatments. Two complementary
      analysis models were used: a multilevel model (MLM) and a continuous Markov
      model. RESULTS: 4862 patients with MS were eligible for the primary analysis
      (mean and median follow-up times 8.7 and 10 years). EDSS worsening was reduced by
      28% (MLM), 7% (Markov) and 24% time-adjusted Markov in the total cohort, and by
      31% (MLM) and 14% (Markov) for relapsing remitting patients. The utility
      worsening was reduced by 23%-24% in the total cohort and by 24%-31% in the RR
      patients depending on the model used. All sensitivity analyses showed a treatment
      effect. There was a 4-year (CI 2.7 to 5.3) delay to EDSS 6.0. An apparent waning
      of treatment effect with time was seen. Subgroup analyses suggested better
      treatment effects in those treated earlier and with lower EDSS scores.
      CONCLUSIONS: This study supports a beneficial effect on long-term disability with
      first-line MS disease-modifying treatments, which is clinically meaningful.
      However the waning effect noted requires further study.

PMID- 30242092
TI  - Targeting the BRD4-HOXB13 Coregulated Transcriptional Networks with Bromodomain
      Kinase Inhibitors to Suppress Metastatic Castration-Resistant Prostate Cancer.
AB  - Resistance to androgen receptor (AR) antagonists is a significant problem in the
      treatment of castration-resistant prostate cancers (CRPC). Identification of the
      mechanisms by which CRPCs evade androgen deprivation therapies (ADT) is critical
      to develop novel therapeutics. We uncovered that CRPCs rely on BRD4-HOXB13
      epigenetic reprogramming for androgen-independent cell proliferation.
      Mechanistically, BRD4, a member of the BET bromodomain family, epigenetically
      promotes HOXB13 expression. Consistently, genetic disruption of HOXB13 or
      pharmacological suppression of its mRNA and protein expression by the novel dual
      activity BET bromodomain-kinase inhibitors directly correlates with rapid
      induction of apoptosis, potent inhibition of tumor cell proliferation and cell
      migration, and suppression of CRPC growth. Integrative analysis revealed that the
      BRD4-HOXB13 transcriptome comprises a proliferative gene network implicated in
      cell-cycle progression, nucleotide metabolism, and chromatin assembly. Notably,
      although the core HOXB13 target genes responsive to BET inhibitors (HOTBIN10) are
      overexpressed in metastatic cases, in ADT-treated CRPC cell lines and patient
      derived circulating tumor cells (CTC) they are insensitive to AR depletion or
      blockade. Among the HOTBIN10 genes, AURKB and MELK expression correlates with
      HOXB13 expression in CTCs of mCRPC patients who did not respond to abiraterone
      (ABR), suggesting that AURKB inhibitors could be used additionally against high
      risk HOXB13-positive metastatic prostate cancers. Combined, our study
      demonstrates that BRD4-HOXB13-HOTBIN10 regulatory circuit maintains the malignant
      state of CRPCs and identifies a core proproliferative network driving ADT
      resistance that is targetable with potent dual-activity bromodomain-kinase
      inhibitors.

PMID- 30242093
TI  - Selective TRK Inhibitor CH7057288 against TRK Fusion-Driven Cancer.
AB  - Members of the tropomyosin receptor kinase (TRK) family are expressed in their
      constitutively activated forms as a result of a gene fusion that occurs across a
      wide variety of cancer types. We have identified CH7057288 as a potent and
      selective TRK inhibitor that belongs to a novel chemical class. CH7057288 showed
      selective inhibitory activity against TRKA, TRKB, and TRKC in cell-free kinase
      assays and suppressed proliferation of TRK fusion-positive cell lines, but not
      that of TRK-negative cell lines. Strong in vivo tumor growth inhibition was
      observed in subcutaneously implanted xenograft tumor models of TRK fusion
      positive cells. Furthermore, in an intracranial implantation model mimicking
      brain metastasis, CH7057288 significantly induced tumor regression and improved
      event-free survival. Recently, resistant mutations in the kinase domain of TRK
      have been reported in patients who show disease progression after treatment with
      the TRK inhibitors now under clinical development. Our compound maintained
      similar levels of in vitro and in vivo activity against one of these resistant
      mutants as it did to wild-type TRK. An X-ray crystal structure of the TRKA and
      CH7057288 complex supported the activity against the mutant. In addition, gene
      expression analysis revealed that CH7057288 suppressed MAPK and E2F pathways as
      downstream signaling of TRK fusion. Therefore, CH7057288 could be a promising
      therapeutic agent for TRK fusion-positive cancer.

PMID- 30242096
TI  - Disseminated nocardiosis with cerebral and subcutaneous lesions on low-dose
      prednisone.
AB  - This case report is of a septuagenarian man on chronic low-dose prednisone who
      presented with disseminated nocardiosis (Nocardia cyriacigeorgica) that was
      initially mistaken for metastatic brain cancer. Neurologists should be aware of
      the potential for opportunistic infections with steroid use and to consider a
      definite tissue diagnosis with culture and histopathology prior to treatment.

PMID- 30242095
TI  - What do adolescents want from their ED? An evaluation on the preferences and
      opinions of adolescents attending local EDs.
AB  - INTRODUCTION: The adolescent population comprises a significant proportion of
      attendances to the ED. Despite adolescent patients reporting lower levels of
      healthcare satisfaction compared with other age groups, their opinions are under
      represented in existing literature. This prospective study investigated
      adolescents' expectations and preferences regarding the ED service. METHODS: A
      questionnaire designed by the investigators was distributed to children aged 12
      16 years over a 6-month period in 2015 at two EDs in the UK. The questionnaire
      explored themes such as same-sex and similar-age areas, staff communication and
      environment. Interviews based on the questionnaire template were also conducted
      and guardians were permitted to accompany the participant. Verbal informed
      consent was obtained from both the young person and their guardian to participate
      in the study. RESULTS: There were 254 respondents, which represented 8.8% of
      adolescent attendances in the study period. 'Cleanliness' was rated the most
      important factor within the ED setting with 94.8% of respondents selecting 4 or 5
      on a 5-point Likert scale. This was followed by 'feeling comfortable', 'clear
      explanation' and 'staff communication' (91.2%, 90.8% and 90.4% rating these 4 or
      5, respectively). However, when participants were asked to select a single most
      important factor, being 'seen quickly' was selected most frequently (95/206,
      46.1%). 'Entertainment' was regarded the least important with only 17.0%
      selecting 4 or 5 on the Likert scale. Preference for being treated in an adult ED
      compared with a child ED increased with age. CONCLUSIONS: Being 'seen quickly'
      was considered the single most important factor by adolescent patients in the ED.
      Notably, 'cleanliness' and aspects of communication also rated highly, with
      'entertainment' regarded as least important. The additional insight into the
      healthcare preferences of the adolescent population provides a platform on which
      the future ED services can be tailored to the needs of young people.

PMID- 30242094
TI  - Nano-delivery of RAD6/Translesion Synthesis Inhibitor SMI#9 for Triple-negative
      Breast Cancer Therapy.
AB  - The triple-negative breast cancer (TNBC) subtype, regardless of their BRCA1
      status, has the poorest outcome compared with other breast cancer subtypes, and
      currently there are no approved targeted therapies for TNBC. We have previously
      demonstrated the importance of RAD6-mediated translesion synthesis pathway in
      TNBC development/progression and chemoresistance, and the potential therapeutic
      benefit of targeting RAD6 with a RAD6-selective small-molecule inhibitor, SMI#9.
      To overcome SMI#9 solubility limitations, we recently developed a gold
      nanoparticle (GNP)-based platform for conjugation and intracellular release of
      SMI#9, and demonstrated its in vitro cytotoxic activity toward TNBC cells. Here,
      we characterized the in vivo pharmacokinetic and therapeutic properties of
      PEGylated GNP-conjugated SMI#9 in BRCA1 wild-type and BRCA1-mutant TNBC xenograft
      models, and investigated the impact of RAD6 inhibition on TNBC metabolism by 1H
      NMR spectroscopy. GNP conjugation allowed the released SMI#9 to achieve higher
      systemic exposure and longer retention as compared with the unconjugated drug.
      Systemically administered SMI#9-GNP inhibited the TNBC growth as effectively as
      intratumorally injected unconjugated SMI#9. Inductively coupled mass spectrometry
      analysis showed highest GNP concentrations in tumors and liver of SMI#9-GNP and
      blank-GNP-treated mice; however, tumor growth inhibition occurred only in the
      SMI#9-GNP-treated group. SMI#9-GNP was tolerated without overt signs of toxicity.
      SMI#9-induced sensitization was associated with perturbation of a common set of
      glycolytic pathways in BRCA1 wild-type and BRCA1-mutant TNBC cells. These data
      reveal novel SMI#9 sensitive markers of metabolic vulnerability for TNBC
      management and suggest that nanotherapy-mediated RAD6 inhibition offers a
      promising strategy for TNBC treatment.

PMID- 30242097
TI  - Rap1 binding to the talin 1 F0 domain makes a minimal contribution to murine
      platelet GPIIb-IIIa activation.
AB  - Activation of platelet glycoprotein IIb-IIIa (GPIIb-IIIa; integrin alphaIIbbeta3)
      leads to high-affinity fibrinogen binding and platelet aggregation during
      hemostasis. Whereas GTP-bound Rap1 GTPase promotes talin 1 binding to the beta3
      cytoplasmic domain to activate platelet GPIIb-IIIa, the Rap1 effector that
      regulates talin association with beta3 in platelets is unknown. Rap1 binding to
      the talin 1 F0 subdomain was proposed to forge the talin 1-Rap1 link in
      platelets. Here, we report a talin 1 point mutant (R35E) that significantly
      reduces Rap1 affinity without a significant effect on its structure or
      expression. Talin 1 head domain (THD) (R35E) was of similar potency to wild-type
      THD in activating alphaIIbbeta3 in Chinese hamster ovary cells. Coexpression with
      activated Rap1b increased activation, and coexpression with Rap1GAP1 reduced
      activation caused by transfection of wild-type THD or THD(R35E). Furthermore,
      platelets from Tln1R35E/R35E mice showed similar GPIIb-IIIa activation to those
      from wild-type littermates in response to multiple agonists. Tln1R35E/R35E
      platelets exhibited slightly reduced platelet aggregation in response to low
      doses of agonists; however, there was not a significant hemostatic defect, as
      judged by tail bleeding times. Thus, the Rap1-talin 1 F0 interaction has little
      effect on platelet GPIIb-IIIa activation and hemostasis and cannot account for
      the dramatic effects of loss of Rap1 activity on these platelet functions.

PMID- 30242098
TI  - Risk-adapted survival benefit of IMRT in early-stage NKTCL: a multicenter study
      from the China Lymphoma Collaborative Group.
AB  - This study evaluated the survival benefit of intensity-modulated radiation
      therapy (IMRT) compared with 3-dimension conformal radiation therapy (3D-CRT) in
      a large national cohort of patients with early-stage extranodal nasal-type
      natural killer/T-cell lymphoma (NKTCL). This retrospective study reviewed
      patients with early-stage NKTCL treated with high-dose radiation therapy (RT;
      >=45 Gy) at 16 Chinese institutions. Patients were stratified into 1 of 4 risk
      groups based on the number of risk factors: low risk (no factors), intermediate
      low risk (1 factor), intermediate-high risk (2 factors), and high-risk (3-5
      factors). Of the 1691 patients, 981 (58%) received IMRT, and 710 (42%) received
      3D-CRT. Unadjusted 5-year overall survival (OS) and progression-free survival
      (PFS) were 75.9% and 67.6%, respectively, for IMRT compared with 68.9% (P = .004)
      and 58.2% (P < .001), respectively, for 3D-CRT. After propensity score match and
      multivariable analyses to account for confounding factors, IMRT remained
      significantly associated with improved OS and PFS. The OS and PFS benefits of
      IMRT persisted in patients treated with modern chemotherapy regimens. Compared
      with 3D-CRT, IMRT significantly improved OS and PFS for high-risk and
      intermediate-high-risk patients but provided limited benefits for low-risk or
      intermediate-low-risk patients. A risk-adapted survival benefit profile of IMRT
      can be used to select patients and make treatment decisions.

PMID- 30242100
TI  - Molecular and clinical analyses of two patients with UPD(16)mat detected by
      screening 94 patients with Silver-Russell syndrome phenotype of unknown
      aetiology.
AB  - BACKGROUND: Recently, a patient with maternal uniparental disomy of chromosome 16
      (UPD(16)mat) presenting with Silver-Russell syndrome (SRS) phenotype was
      reported. SRS is characterised by growth failure and dysmorphic features.
      OBJECTIVE: To clarify the prevalence of UPD(16)mat in aetiology-unknown patients
      with SRS phenotype and phenotypic differences between UPD(16)mat and SRS.
      METHODS: We studied 94 patients with SRS phenotype of unknown aetiology. Sixty
      three satisfied the Netchine-Harbison clinical scoring system (NH-CSS) criteria,
      and 25 out of 63 patients showed both protruding forehead and relative
      macrocephaly (clinical SRS). The remaining 31 patients met only three NH-CSS
      criteria, but were clinically suspected as having SRS. To detect UPD(16)mat, we
      performed methylation analysis for the ZNF597:TSS-differentially methylated
      region (DMR) on chromosome 16 and subsequently performed microsatellite, SNP
      array and exome analyses in the patients with hypomethylated ZNF597:TSS-DMR.
      RESULTS: We identified two patients (2.1%) with a mixture of maternal isodisomy
      and heterodisomy of chromosome 16 in 94 aetiology-unknown patients with SRS
      phenotype. Both patients exhibited preterm birth and prenatal and postnatal
      growth failure. The male patient had ventricular septal defect and hypospadias.
      Whole-exome sequencing detected no gene mutations related to their phenotypes.
      CONCLUSION: We suggest considering genetic testing for UPD(16)mat in SRS
      phenotypic patients without known aetiology.

PMID- 30242101
TI  - Leveraging the power of new molecular technologies in the clinical setting
      requires unprecedented awareness of limitations and drawbacks: experience of one
      diagnostic laboratory.
AB  - BACKGROUND: Advances in molecular technologies and in-silico variant prediction
      tools offer wide-ranging opportunities in diagnostic settings, yet they also
      present with significant limitations. OBJECTIVE: Here, we contextualise the
      limitations of next-generation sequencing (NGS), multiplex ligation-dependent
      probe amplification (MLPA) and in-silico prediction tools routinely used by
      diagnostic laboratories by reviewing specific experiences from our diagnostic
      laboratory. METHODS: We investigated discordant annotations and/or incorrect
      variant 'callings' in exons of 56 genes constituting our cardiomyopathy and
      connective tissue disorder NGS panels. Discordant variants and segmental
      duplications (SD) were queried using the National Center for Biotechnology
      Information (NCBI) Basic Local Alignment Search Tool and the University of
      California Santa Cruz genome browser, respectively, to identify regions of high
      homology. Discrepant variant analyses by in-silico models were re-evaluated using
      updated file entries. RESULTS: We observed a 5% error rate in MYH7 variant
      'calling' using MLPA, which resulted from >90% homology of the MYH7 probe-binding
      site to MYH6. SDs were detected in TTN, PKP2 and MYLK. SDs in MYLK presented the
      highest risk (15.7%) of incorrect variant 'calling'. The inaccurate 'callings'
      and discrepant in-silico predictions were resolved following detailed
      investigation into the source of error. CONCLUSION: Recognising the limitations
      described here may help avoid incorrect diagnoses and leverage the power of new
      molecular technologies in diagnostic settings.

PMID- 30242099
TI  - Imetelstat, a telomerase inhibitor, is capable of depleting myelofibrosis stem
      and progenitor cells.
AB  - Clinical trials of imetelstat therapy have indicated that this telomerase
      inhibitor might have disease-modifying effects in a subset of patients with
      myelofibrosis (MF). The mechanism by which imetelstat induces such clinical
      responses has not been clearly elucidated. Using in vitro hematopoietic
      progenitor cell (HPC) assays and in vivo hematopoietic stem cell (HSC) assays, we
      examined the effects of imetelstat on primary normal and MF HSCs/HPCs. Treatment
      of CD34+ cells with imetelstat reduced the numbers of MF but not cord blood HPCs
      (colony-forming unit-granulocyte/macrophage, burst-forming unit-erythroid, and
      colony-forming unit-granulocyte/erythroid/macrophage/megakaryocyte) as well as MF
      but not normal CD34+ALDH+ cells irrespective of the patient's mutational status.
      Moreover, imetelstat treatment resulted in depletion of mutated HPCs from
      JAK2V617F+ MF patients. Furthermore, treatment of immunodeficient mice that had
      been previously transplanted with MF splenic CD34+ cells with imetelstat at a
      dose of 15 mg/kg, 3 times per week for 4 weeks had a limited effect on the degree
      of chimerism achieved by normal severe combined immunodeficiency repopulating
      cells but resulted in a significant reduction in the degree of human MF cell
      chimerism as well as the proportion of mutated donor cells. These effects were
      sustained for at least 3 months after drug treatment was discontinued. These
      actions of imetelstat on MF HSCs/HPCs were associated with inhibition of
      telomerase activity and the induction of apoptosis. Our findings indicate that
      the effects of imetelstat therapy observed in MF patients are likely attributable
      to the greater sensitivity of imetelstat against MF as compared with normal
      HSCs/HPCs as well as the intensity of the imetelstat dose schedule.

PMID- 30242102
TI  - Gabepentinoids and Benzodiazepines in Medicare Part D.

PMID- 30242103
TI  - Authors' Reply.

PMID- 30242104
TI  - Disrupting Hedgehog Cardin-Weintraub sequence and positioning changes cellular
      differentiation and compartmentalization in vivo.
AB  - Metazoan Hedgehog (Hh) morphogens are essential regulators of growth and
      patterning at significant distances from their source, despite being produced as
      N-terminally palmitoylated and C-terminally cholesteroylated proteins, which
      firmly tethers them to the outer plasma membrane leaflet of producing cells and
      limits their spread. One mechanism to overcome this limitation is proteolytic
      processing of both lipidated terminal peptides, called shedding, but molecular
      target site requirements for effective Hh shedding remained undefined. In this
      work, by using Drosophila melanogaster as a model, we show that mutagenesis of
      the N-terminal Cardin-Weintraub (CW) motif inactivates recombinant Hh proteins to
      variable degrees and, if overexpressed in the same compartment, converts them
      into suppressors of endogenous Hh function. In vivo, additional removal of N
      palmitate membrane anchors largely restored endogenous Hh function, supporting
      the hypothesis that proteolytic CW processing controls Hh solubilization.
      Importantly, we also observed that CW repositioning impairs anterior/posterior
      compartmental boundary maintenance in the third instar wing disc. This
      demonstrates that Hh shedding not only controls the differentiation of anterior
      cells, but also maintains the sharp physical segregation between these receiving
      cells and posterior Hh-producing cells.

PMID- 30242106
TI  - Dyspareunia: consider urogenital prolapse.

PMID- 30242105
TI  - An interview with James Sharpe.
AB  - James Sharpe is a developmental biologist who studies the process of limb
      development using a multi-disciplinary approach, combining experimental systems,
      imaging and computer modelling. Formerly based at the Centre for Genomic
      Regulation in Barcelona, James was recently appointed Head of EMBL Barcelona. We
      caught up with James at the British Society for Developmental Biology Spring
      Meeting to ask him about his research, his thoughts on computational modelling,
      and his vision for the new EMBL Barcelona site.

PMID- 30242107
TI  - Risk factors for patellofemoral pain: a systematic review and meta-analysis.
AB  - BACKGROUND: Patellofemoral pain (PFP) is a prevalent condition commencing at
      various points throughout life. We aimed to provide an evidence synthesis
      concerning predictive variables for PFP, to aid development of preventative
      interventions. METHODS: We searched Medline, Web of Science and SCOPUS until
      February 2017 for prospective studies investigating at least one potential risk
      factor for future PFP. Two independent reviewers appraised methodological quality
      using the Newcastle-Ottawa Scale. We conducted meta-analysis where appropriate,
      with standardised mean differences (SMD) and risk ratios calculated for
      continuous and nominal scaled data. RESULTS: This review included 18 studies
      involving 4818 participants, of whom 483 developed PFP (heterogeneous incidence
      10%). Three distinct subgroups (military recruits, adolescents and recreational
      runners) were identified. Strong to moderate evidence indicated that age, height,
      weight, body mass index (BMI), body fat and Q angle were not risk factors for
      future PFP. Moderate evidence indicated that quadriceps weakness was a risk
      factor for future PFP in the military, especially when normalised by BMI (SMD 
      0.69, CI -1.02, -0.35). Moderate evidence indicated that hip weakness was not a
      risk factor for future PFP (multiple pooled SMDs, range -0.09 to -0.20), but in
      adolescents, moderate evidence indicated that increased hip abduction strength
      was a risk factor for future PFP (SMD 0.71, CI 0.39, 1.04). CONCLUSIONS: This
      review identified multiple variables that did not predict future PFP, but
      quadriceps weakness in military recruits and higher hip strength in adolescents
      were risk factors for PFP. Identifying modifiable risk factors is an urgent
      priority to improve prevention and treatment outcomes.

PMID- 30242108
TI  - NPC1L1-dependent intestinal cholesterol absorption requires ganglioside GM3 in
      membrane microdomains.
AB  - Intestinal cholesterol absorption is a key regulator of systemic cholesterol
      homeostasis. Excessive dietary cholesterol and its intestinal uptake lead to
      hypercholesterolemia, a major risk factor for cardiovascular disease. Intestinal
      cholesterol uptake is mediated by Niemann-Pick C1-like 1 (NPC1L1), a
      transmembrane protein localized in membrane microdomains (lipid rafts) enriched
      in gangliosides and cholesterol. The roles of gangliosides, such as
      monosialodihexosylganglioside (GM3) and its synthesizing enzyme GM3 synthase
      (GM3S), in NPC1L1-dependent cholesterol uptake have not been examined previously.
      Here, we examined NPC1L1-dependent cholesterol uptake in a cell model as well as
      in wild-type and apoE-deficient mice fed normal or high-cholesterol diets. We
      showed that NPC1L1-dependent cholesterol uptake was impaired in GM3S-deficient
      cells and that GM3S deficiency promoted resistance to hypercholesterolemia in
      both wild-type and apoE-deficient mice fed the high-cholesterol but not the
      normal diet. Our findings suggest that GM3 and related gangliosides are essential
      for NPC1L1-mediated intestinal cholesterol absorption and are potential targets
      for hypercholesterolemia therapy.

PMID- 30242110
TI  - High-throughput serum N-glycomics: method comparison and application to study
      rheumatoid arthritis and pregnancy-associated changes.
AB  - N-Glycosylation is a fundamentally important protein modification with a major
      impact on glycoprotein characteristics such as serum half-life and receptor
      interaction. More than half of the proteins in human serum are glycosylated, and
      the relative abundances of protein glycoforms often reflect alterations in health
      and disease. Several analytical methods are currently capable of analyzing the
      total serum N-glycosylation in a high-throughput manner.Here we evaluate and
      compare the performance of three high-throughput released N-glycome analysis
      methods. Included were hydrophilic-interaction ultra-high-performance liquid
      chromatography with fluorescence detection (HILIC-UHPLC-FLD) with 2
      aminobenzamide labeling of the glycans, multiplexed capillary gel electrophoresis
      with laser-induced fluorescence detection (xCGE-LIF) with 8-aminopyrene-1-3,6
      trisulfonic acid labeling, and matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOF-MS) with linkage-specific sialic acid
      esterification. All methods assessed the same panel of serum samples, which were
      obtained at multiple time points during the pregnancies and postpartum periods of
      healthy women and patients with rheumatoid arthritis (RA). We compared the
      analytical methods on their technical performance as well as on their ability to
      describe serum protein N-glycosylation changes throughout pregnancy, with RA, and
      with RA disease activity.Overall, the methods proved to be similar in their
      detection and relative quantification of serum protein N-glycosylation. However,
      the non-MS methods showed superior repeatability over MALDI-TOF-MS, and allowed
      the best structural separation of low-complexity N-glycans. MALDI-TOF-MS achieved
      the highest throughput and provided compositional information on higher
      complexity N-glycans. Consequentially, MALDI-TOF-MS could establish the linkage
      specific sialylation differences within pregnancy and RA, whereas HILIC-UHPLC-FLD
      and xCGE-LIF demonstrated differences in alpha1,3- and alpha1,6-branch
      galactosylation. While the combination of methods proved to be the most
      beneficial for the analysis of total serum protein N-glycosylation, informed
      method choices can be made for the glycosylation analysis of single proteins or
      samples of varying complexity.

PMID- 30242109
TI  - Bicuspid aortic valve formation: Nos3 mutation leads to abnormal lineage
      patterning of neural crest cells and the second heart field.
AB  - The bicuspid aortic valve (BAV), a valve with two instead of three aortic
      leaflets, belongs to the most prevalent congenital heart diseases in the world,
      occurring in 0.5-2% of the general population. We aimed to understand how changes
      in early cellular contributions result in BAV formation and impact cardiovascular
      outflow tract development. Detailed 3D reconstructions, immunohistochemistry and
      morphometrics determined that, during valvulogenesis, the non-coronary leaflet
      separates from the parietal outflow tract cushion instead of originating from an
      intercalated cushion. Nos3-/- mice develop a BAV without a raphe as a result of
      incomplete separation of the parietal outflow tract cushion into the right and
      non-coronary leaflet. Genetic lineage tracing of endothelial, second heart field
      and neural crest cells revealed altered deposition of neural crest cells and
      second heart field cells within the parietal outflow tract cushion of Nos3-/-
      embryos. The abnormal cell lineage distributions also affected the positioning of
      the aortic and pulmonary valves at the orifice level. The results demonstrate
      that the development of the right and non-coronary leaflets are closely related.
      A small deviation in the distribution of neural crest and second heart field
      populations affects normal valve formation and results in the predominant right
      non-type BAV in Nos3-/- mice.

PMID- 30242111
TI  - Integrated proteomics reveals apoptosis-related mechanisms associated with
      placental malaria.
AB  - Malaria in pregnancy is a public health concern in malaria-endemic areas.
      Accumulation of maternal immune cells in the placenta and increased levels of
      inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected
      erythrocytes have been associated to poor neonatal outcomes, including low birth
      weight due to fetal growth restriction. Little is known about the molecular
      changes occurring in a P. falciparum-infected placenta that has developed
      placental malaria during pregnancy but had the parasites cleared by
      pharmacological treatment (past infection). We conducted an integrated proteome,
      phosphoproteome and glycoproteome analysis in past P. falciparum-infected
      placentas aiming to find molecular changes associated with placental malaria. A
      total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were
      identified and quantified in this study, disclosing overrepresented processes
      related to oxidative stress, protein folding and regulation of apoptosis in past
      infected placentas Moreover, AKT and ERK signaling pathways activation, together
      with clinical data, were further correlated to an increased apoptosis in past
      infected placentas. This study showed apoptosis-related mechanisms associated
      with placental malaria that can be further explored as therapeutic target against
      adverse pregnancy outcomes.

PMID- 30242113
TI  - CAMKK2 Promotes Prostate Cancer Independently of AMPK via Increased Lipogenesis.
AB  - New targets are required for treating prostate cancer, particularly castrate
      resistant disease. Previous studies reported that calcium/calmodulin-dependent
      protein kinase kinase 2 (CAMKK2) expression is increased in human prostate
      cancer. Here, we show that Camkk2 deletion or pharmacologic inhibition protects
      against prostate cancer development in a preclinical mouse model that lacks
      expression of prostate-specific Pten. In contrast, deletion of AMP-activated
      protein kinase (Ampk) beta1 resulted in earlier onset of adenocarcinoma
      development. These findings suggest for the first time that Camkk2 and Ampk have
      opposing effects in prostate cancer progression. Loss of CAMKK2 in vivo or in
      human prostate cancer cells reduced the expression of two key lipogenic enzymes,
      acetyl-CoA carboxylase and fatty acid synthase. This reduction was mediated via a
      posttranscriptional mechanism, potentially involving a decrease in protein
      translation. Moreover, either deletion of CAMKK2 or activation of AMPK reduced
      cell growth in human prostate cancer cells by inhibiting de novo lipogenesis.
      Activation of AMPK in a panel of human prostate cancer cells inhibited cell
      proliferation, migration, and invasion as well as androgen-receptor signaling.
      These findings demonstrate that CAMKK2 and AMPK have opposing effects on
      lipogenesis, providing a potential mechanism for their contrasting effects on
      prostate cancer progression in vivo They also suggest that inhibition of CAMKK2
      combined with activation of AMPK would offer an efficacious therapeutic strategy
      in treatment of prostate cancer.Significance: These findings show that CAMKK2 and
      its downstream target AMPK have opposing effects on prostate cancer development
      and raise the possibility of a new combined therapeutic approach that inhibits
      CAMKK2 and activates AMPK. Cancer Res; 78(24); 1-15. (c)2018 AACR.

PMID- 30242112
TI  - Downregulation of Dipeptidyl Peptidase 4 Accelerates Progression to Castration
      Resistant Prostate Cancer.
AB  - The standard treatment for metastatic prostate cancer, androgen deprivation
      therapy (ADT), is designed to suppress androgen receptor (AR) activity. However,
      men invariably progress to castration-resistant prostate cancer (CRPC), and AR
      reactivation contributes to progression in most cases. To identify mechanisms
      that may drive CRPC, we examined a VCaP prostate cancer xenograft model as tumors
      progressed from initial androgen sensitivity prior to castration to castration
      resistance and then on to relapse after combined therapy with further AR-targeted
      drugs (abiraterone plus enzalutamide). AR activity persisted in castration
      resistant and abiraterone/enzalutamide-resistant xenografts and was associated
      with increased expression of the AR gene and the AR-V7 splice variant. We then
      assessed expression of individual AR-regulated genes to identify those that
      persisted, thereby contributing to tumor growth, versus those that decreased and
      may therefore exhibit tumor suppressor activities. The most significantly
      decreased AR target gene was dipeptidyl peptidase 4 (DPP4), which encodes a
      membrane-anchored protein that cleaves dipeptides from multiple growth factors,
      resulting in their increased degradation. DPP4 mRNA and protein were also
      decreased in clinical CRPC cases, and inhibition of DPP4 with sitagliptin
      enhanced the growth of prostate cancer xenografts following castration.
      Significantly, DPP4 inhibitors are frequently used to treat type 2 diabetes as
      they increase insulin secretion. Together, these results implicate DPP4 as an AR
      regulated tumor suppressor gene whose loss enhances growth factor activity and
      suggest that treatment with DPP4 inhibitors may accelerate emergence of
      resistance to ADT.Significance: These findings identify DPP4 as an AR-stimulated
      tumor suppressor gene that is downregulated during progression to castration
      resistant prostate cancer, warning that treatment with DPP4 inhibitors, commonly
      used to treat type 2 diabetes, may accelerate prostate cancer progression
      following androgen deprivation therapy. Cancer Res; 78(22); 6354-62. (c)2018
      AACR.

PMID- 30242114
TI  - Roles for ER:endosome membrane contact sites in ligand-stimulated intraluminal
      vesicle formation.
AB  - Multivesicular endosomes/bodies (MVBs) sort membrane proteins between recycling
      and degradative pathways. Segregation of membrane proteins onto intraluminal
      vesicles (ILVs) of MVBs removes them from the recycling pathway and facilitates
      their degradation following fusion of MVBs with lysosomes. Sorting of many cargos
      onto ILVs depends on the ESCRT (Endosomal Sorting Complex Required for Transport)
      machinery, although ESCRT-independent mechanisms also exist. In mammalian cells,
      efficient sorting of ligand-stimulated epidermal growth factor receptors onto
      ILVs also depends on the tyrosine phosphatase, PTP1B, an ER-localised enzyme that
      interacts with endosomal targets at membrane contacts between MVBs and the ER.
      This review focuses on the potential roles played by ER:MVB membrane contact
      sites in regulating ESCRT-dependent ILV formation.

PMID- 30242116
TI  - Lipids and lipid domains of the yeast vacuole.
AB  - The membrane raft has been a focus of intensive research for the past two
      decades. Liquid-ordered domains form in artificial liposomes containing sterol
      and saturated lipids, but their presence in living cell membranes has been
      controversial. The yeast vacuole is exceptional in that micron-sized raft-like
      domains form in the stationary phase and under several other conditions. The
      sterol content of the vacuole in the log phase is much lower than that of
      liposomes showing liquid-ordered domains, suggesting that sterols may need to be
      supplied to the vacuole for the raft-like domain formation. We will discuss how
      lipids and lipid domains are organized in the vacuolar membrane and examine
      whether evidence is strong enough to conclude that the observed micron-sized
      domains are rafts.

PMID- 30242117
TI  - Protein structure and computational drug discovery.
AB  - The first protein structures revealed a complex web of weak interactions
      stabilising the three-dimensional shape of the molecule. Small molecule ligands
      were then found to exploit these same weak binding events to modulate protein
      function or act as substrates in enzymatic reactions. As the understanding of
      ligand-protein binding grew, it became possible to firstly predict how and where
      a particular small molecule might interact with a protein, and then to identify
      putative ligands for a specific protein site. Computer-aided drug discovery,
      based on the structure of target proteins, is now a well-established technique
      that has produced several marketed drugs. We present here an overview of the
      various methodologies being used for structure-based computer-aided drug
      discovery and comment on possible future developments in the field.

PMID- 30242115
TI  - The creatine kinase system as a therapeutic target for myocardial ischaemia
      reperfusion injury.
AB  - Restoring blood flow following an acute myocardial infarction saves lives, but
      results in tissue damage due to ischaemia-reperfusion injury (I/R). Ameliorating
      this damage is a major research goal to improve recovery and reduce subsequent
      morbidity due to heart failure. Both the ischaemic and reperfusion phases
      represent crises of cellular energy provision in which the mitochondria play a
      central role. This mini-review will explore the rationale and therapeutic
      potential of augmenting the creatine kinase (CK) energy shuttle, which
      constitutes the primary short-term energy buffer and transport system in the
      cardiomyocyte. Proof-of-principle data from several transgenic mouse models have
      demonstrated robust cardioprotection by either raising myocardial creatine levels
      or by overexpressing specific CK isoforms. The effect on cardiac function, high
      energy phosphates and myocardial injury will be discussed and possible directions
      for future research highlighted. We conclude that the CK system represents a
      viable target for therapeutic intervention in I/R injury; however, much needed
      translational studies will require the development of new pharmacological tools.

PMID- 30242118
TI  - Emerging role of extracellular vesicles in mediating cancer cachexia.
AB  - Cancer cachexia is a multifactorial metabolic syndrome characterized by the rapid
      loss of skeletal muscle mass with or without the loss of fat mass. Nearly 50-80%
      of all cancer patients' experience rapid weight loss results in ~20% of cancer
      related deaths. The levels of pro-inflammatory and pro-cachectic factors were
      significantly up-regulated in cachexia patients when compared with the patients
      who were without cachexia. It is becoming evident that these factors work
      synergistically to induce cancer cachexia. Extracellular vesicles (EVs) including
      exosomes and microvesicles are implicated in cell-cell communication, immune
      response, tissue repair, epigenetic regulation, and in various diseases including
      cancer. It has been reported that these EVs regulate cancer progression,
      metastasis, organotropism and chemoresistance. In recent times, the role of EVs
      in regulating cancer cachexia is beginning to unravel. The aim of this mini
      article is to review the recent knowledge gained in the field of EVs and cancer
      cachexia. Specifically, the role of tumour cell-derived EVs in promoting
      catabolism in distally located skeletal muscles and adipose tissue will be
      discussed.

PMID- 30242119
TI  - The Golgi architecture and cell sensing.
AB  - An array of signalling molecules are located at the Golgi apparatus, including
      phosphoinositides, small GTPases, kinases, and phosphatases, which are linked to
      multiple signalling pathways. Initially considered to be associated predominantly
      with membrane trafficking, signalling pathways at the Golgi are now recognised to
      regulate a diverse range of higher-order functions. Many of these signalling
      pathways are influenced by the architecture of the Golgi. In vertebrate cells,
      the Golgi consists of individual stacks fused together into a compact ribbon
      structure and the function of this ribbon structure has been enigmatic. Notably,
      recent advances have identified a role for the Golgi ribbon in regulation of
      cellular processes. Fragmentation of the Golgi ribbon results in modulation of
      many signalling pathways. Various diseases and disorders, including cancer and
      neurodegeneration, are associated with the loss of the Golgi ribbon and the
      appearance of a dispersed fragmented Golgi. Here, we review the emerging theme of
      the Golgi as a cell sensor and highlight the relationship between the
      morphological status of the Golgi in vertebrate cells and the modulation of
      signalling networks.

PMID- 30242120
TI  - Extracellular vesicles: translational challenges and opportunities.
AB  - Extracellular vesicles (EVs) are a heterogeneous group of small lipid-enclosed
      structures with myriad roles in physiology and disease. The recent surge of
      interest in EVs has led to greater understanding of their biology and
      appreciation of how they might be utilised as diagnostic and therapeutic tools.
      There remain, however, a number of challenges that must be overcome before EVs
      may be used routinely in the clinic. In this review we will discuss the
      translational potential of EVs and the current technologies available to isolate,
      purify and analyse EVs and their contents.

PMID- 30242121
TI  - Cell cycle-dependent phosphorylation and regulation of cellular differentiation.
AB  - Embryogenesis requires an exquisite regulation of cell proliferation, cell cycle
      withdrawal and differentiation into a massively diverse range of cells at the
      correct time and place. Stem cells also remain to varying extents in different
      adult tissues, acting in tissue homeostasis and repair. Therefore, regulated
      proliferation and subsequent differentiation of stem and progenitor cells remains
      pivotal throughout life. Recent advances have characterised the cell cycle
      dynamics, epigenetics, transcriptome and proteome accompanying the transition
      from proliferation to differentiation, revealing multiple bidirectional
      interactions between the cell cycle machinery and factors driving
      differentiation. Here, we focus on a direct mechanistic link involving
      phosphorylation of differentiation-associated transcription factors by cell cycle
      associated Cyclin-dependent kinases. We discuss examples from the three embryonic
      germ layers to illustrate this regulatory mechanism that co-ordinates the balance
      between cell proliferation and differentiation.

PMID- 30242122
TI  - High-resolution studies of lysis-lysogeny decision making in bacteriophage
      lambda.
AB  - Cellular decision-making guides complex development such as cell differentiation
      and disease progression. Much of our knowledge about decision-making is derived
      from simple models, such as bacteriophage lambda infection, in which lambda
      chooses between the vegetative lytic fate and the dormant lysogenic fate. This
      paradigmatic system is broadly understood but lacking mechanistic details, partly
      due to limited resolution of past studies. Here, we discuss how modern
      technologies have enabled high-resolution examination of lambda decision-making
      to provide new insights and exciting possibilities in studying this classical
      system. The advent of techniques for labeling specific DNA, RNA, and proteins in
      cells allows for molecular-level characterization of events in lambda
      development. These capabilities yield both new answers and new questions
      regarding how the isolated lambda genetic circuit acts, what biological events
      transpire among phages in their natural context, and how the synergy of simple
      phage macromolecules brings about complex behaviors.

PMID- 30242123
TI  - Functional and structural characterization of the chikungunya virus translational
      recoding signals.
AB  - Climate change and human globalization have spurred the rapid spread of mosquito
      borne diseases to naive populations. One such emerging virus of public health
      concern is chikungunya virus (CHIKV), a member of the Togaviridae family, genus
      Alphavirus CHIKV pathogenesis is predominately characterized by acute febrile
      symptoms and severe arthralgia, which can persist in the host long after viral
      clearance. CHIKV has also been implicated in cases of acute encephalomyelitis,
      and its vertical transmission has been reported. Currently, no FDA-approved
      treatments exist for this virus. Recoding elements help expand the coding
      capacity in many viruses and therefore represent potential therapeutic targets in
      antiviral treatments. Here, we report the molecular and structural
      characterization of two CHIKV translational recoding signals: a termination codon
      read-through (TCR) element located between the nonstructural protein 3 and 4
      genes and a programmed -1 ribosomal frameshift (-1 PRF) signal located toward the
      3' end of the CHIKV 6K gene. Using Dual-Luciferase and immunoblot assays in
      HEK293T and U87MG mammalian cell lines, we validated and genetically
      characterized efficient TCR and -1 PRF. Analyses of RNA chemical modification
      data with selective 2'-hydroxyl acylation and primer extension (SHAPE) assays
      revealed that CHIKV -1 PRF is stimulated by a tightly structured, triple-stem
      hairpin element, consistent with previous observations in alphaviruses, and that
      the TCR signal is composed of a single large multibulged hairpin element. These
      findings illuminate the roles of RNA structure in translational recoding and
      provide critical information relevant for design of live-attenuated vaccines
      against CHIKV and related viruses.

PMID- 30242124
TI  - The microRNA-23a cluster regulates the developmental HoxA cluster function during
      osteoblast differentiation.
AB  - MicroRNAs (miRs) and Hox transcription factors have decisive roles in postnatal
      bone formation and homeostasis. In silico analysis identified extensive
      interaction between HOXA cluster mRNA and microRNAs from the miR-23a cluster.
      However, Hox regulation by the miR-23a cluster during osteoblast differentiation
      remains undefined. We examined this regulation in preosteoblasts and in a novel
      miR-23a cluster knockdown mouse model. Overexpression and knockdown of the miR
      23a cluster in preosteoblasts decreased and increased, respectively, the
      expression of the proteins HOXA5, HOXA10, and HOXA11; these proteins' mRNAs
      exhibited significant binding with the miR-23a cluster miRNAs, and miRNA 3'-UTR
      reporter assays confirmed repression. Importantly, during periods correlating
      with development and differentiation of bone cells, we found an inverse pattern
      of expression between HoxA factors and members of the miR-23a cluster. HOXA5 and
      HOXA11 bound to bone-specific promoters, physically interacted with transcription
      factor RUNX2, and regulated bone-specific genes. Depletion of HOXA5 or HOXA11 in
      preosteoblasts also decreased cellular differentiation. Additionally, stable
      overexpression of the miR-23a cluster in osteoblasts decreased the recruitment of
      HOXA5 and HOXA11 to osteoblast gene promoters, significantly inhibiting histone
      H3 acetylation. Heterozygous miR-23a cluster knockdown female mice (miR-23a
      ClWT/ZIP) had significantly increased trabecular bone mass when compared with WT
      mice. Furthermore, miR-23a cluster knockdown in calvarial osteoblasts of these
      mice increased the recruitment of HOXA5 and HOXA11, with a substantial enrichment
      of promoter histone H3 acetylation. Taken together, these findings demonstrate
      that the miR-23a cluster is required for maintaining stage-specific HoxA factor
      expression during osteogenesis.

PMID- 30242125
TI  - Structural disorder in four-repeat Tau fibrils reveals a new mechanism for
      barriers to cross-seeding of Tau isoforms.
AB  - The intracellular deposition of fibrils composed of the microtubule-associated
      protein Tau is a characteristic feature of Alzheimer's disease (AD) and other
      fatal neurodegenerative disorders collectively known as tauopathies. Short Tau
      fibrils spread intracerebrally through transfer between interconnected neurons.
      Once taken up by a recipient cell, Tau fibrils recruit Tau monomers onto their
      ends. Based on the number of microtubule-binding repeats, there are two distinct
      groups of Tau isoforms: three-repeat (3R) Tau and four-repeat (4R) Tau. In AD,
      all Tau isoforms are deposited, whereas in other tauopathies, only 3R or 4R Tau
      isoforms are deposited. The molecular basis for these isoform-specific
      depositions is poorly understood, although conformation-based cross-seeding
      barriers are key. Here, we used sedimentation assays, EPR spectroscopy, and other
      structural readouts to better understand the cross-seeding barriers of 4R Tau
      fibrils. We observed that fibrils formed from truncated Tau (K18), but not full
      length Tau (htau40), exhibit a barrier that inhibits 3R Tau recruitment.
      Investigating an array of differently sized fragments, we found that the Tau C
      terminus modulates the cross-seeding barrier and that the N terminus plays a
      synergistic role. Two disease-associated Tau variants, P301S and P301L, also
      established strong cross-seeding barriers. EPR analysis indicated that fibrils
      seeded with truncated and mutated Tau, but not htau40, are structurally
      disordered in the second half of repeat four and onward. These findings suggest
      that the disorder in this region diminishes the ability of 4R Tau fibrils to
      recruit 3R Tau monomers, revealing a new mechanism for Tau cross-seeding
      barriers.

PMID- 30242126
TI  - The effects of CD14 and IL-27 on induction of endotoxin tolerance in human
      monocytes and macrophages.
AB  - Upon repeated exposure to endotoxin or lipopolysaccharide (LPS), myeloid cells
      enter a refractory state called endotoxin tolerance as a homeostatic mechanism.
      In innate immune cells, LPS is recognized by co-receptors Toll-like receptor 4
      (TLR4) and CD-14 to initiate an inflammatory response for subsequent cytokine
      production. One such cytokine, interleukin (IL)-27, is produced by myeloid cells
      in response to bacterial infection. In monocytes, IL-27 has proinflammatory
      functions such as up-regulating TLR4 expression for enhanced LPS-mediated
      cytokine production; alternatively, IL-27 induces inhibitory functions in
      activated macrophages. This study investigated the effects of IL-27 on the
      induction of endotoxin tolerance in models of human monocytes compared with
      macrophages. Our data demonstrate that IL-27 inhibits endotoxin tolerance by up
      regulating cell surface TLR4 expression and soluble CD14 production to mediate
      stability of the surface LPS-TLR4-CD14 complex in THP-1 cells. In contrast,
      elevated basal expression of membrane-bound CD14 in phorbol 12-myristate 13
      acetate (PMA)-THP-1 cells, primary monocytes, and primary macrophages may promote
      CD14-mediated endocytosis and be responsible for the preservation of an endotoxin
      tolerized state in the presence of IL-27. Overall, the efficacy of IL-27 in
      inhibiting endotoxin tolerance in human THP-1 monocytes and PMA-THP-1 macrophages
      is affected by membrane-bound and soluble CD14 expression.

PMID- 30242127
TI  - Chromophorylation of cyanobacteriochrome Slr1393 from Synechocystis sp. PCC 6803
      is regulated by protein Slr2111 through allosteric interaction.
AB  - Cyanobacteriochromes (CBCRs) are photochromic proteins in cyanobacteria that act
      as photosensors. CBCRs bind bilins as chromophores and sense nearly the entire
      visible spectrum of light, but the regulation of the chromophorylation of CBCRs
      is unknown. Slr1393 from Synechocystis sp. PCC 6803 is a CBCR containing three
      consecutive GAF (cGMP phosphodiesterase, adenylyl cyclase, and FhlA protein)
      domains, of which only the third one (Slr1393g3) can be phycocyanobilin
      chromophorylated. The protein Slr2111 from Synechocystis sp. PCC 6803 includes a
      cystathionine beta-synthase (CBS) domain pair of an as yet unknown function at
      its N terminus. CBS domains are often characterized as sensors of cellular energy
      status by binding nucleotides. In this work, we demonstrate that Slr2111 strongly
      interacts with Slr1393 in vivo and in vitro, which generates a complex in a 1:1
      molar ratio. This tight interaction inhibits the chromophorylation of Slr1393g3,
      even if the chromophore is present. Instead, the complex stability and thereby
      the chromophorylation of Slr1393 are regulated by the binding of nucleotides
      (ATP, ADP, AMP) to the CBS domains of Slr2111 with varying affinities. It is
      demonstrated that residues Asp-53 and Arg-97 of Slr2111 are involved in
      nucleotide binding. While ATP binds to Slr2111, the association between the two
      proteins gets weaker and chromophorylation of Slr1393 are enabled. In contrast,
      AMP binding to Slr2111 leads to a stronger association, thereby inhibiting the
      chromophorylation. It is concluded that Slr2111 acts as a sensor of the cellular
      energy status that regulates the chromophorylation of Slr1393 and thereby its
      function as a light-driven histidine kinase.

PMID- 30242128
TI  - Dynamic disulfide exchange in a crystallin protein in the human eye lens promotes
      cataract-associated aggregation.
AB  - Increased light scattering in the eye lens due to aggregation of the long-lived
      lens proteins, crystallins, is the cause of cataract disease. Several mutations
      in the gene encoding human gammaD-crystallin (HgammaD) cause misfolding and
      aggregation. Cataract-associated substitutions at Trp42 cause the protein to
      aggregate in vitro from a partially unfolded intermediate locked by an internal
      disulfide bridge, and proteomic evidence suggests a similar aggregation precursor
      is involved in age-onset cataract. Surprisingly, WT HgammaD can promote
      aggregation of the W42Q variant while itself remaining soluble. Here, a search
      for a biochemical mechanism for this interaction has revealed a previously
      unknown oxidoreductase activity in HgammaD. Using in vitro oxidation, mutational
      analysis, cysteine labeling, and MS, we have assigned this activity to a redox
      active internal disulfide bond that is dynamically exchanged among HgammaD
      molecules. The W42Q variant acts as a disulfide sink, reducing oxidized WT and
      forming a distinct internal disulfide that kinetically traps the aggregation
      prone intermediate. Our findings suggest a redox "hot potato" competition among
      WT and mutant or modified polypeptides wherein variants with the lowest kinetic
      stability are trapped in aggregation-prone intermediate states upon accepting
      disulfides from more stable variants. Such reactions may occur in other long
      lived proteins that function in oxidizing environments. In these cases,
      aggregation may be forestalled by inhibiting disulfide flow toward mutant or
      damaged polypeptides.

PMID- 30242129
TI  - Complex formation of sphingomyelin synthase 1 with glucosylceramide synthase
      increases sphingomyelin and decreases glucosylceramide levels.
AB  - Sphingolipids, including sphingomyelin (SM) and glucosylceramide (GlcCer), are
      generated by the addition of a polar head group to ceramide (Cer). Sphingomyelin
      synthase 1 (SMS1) and glucosylceramide synthase (GCS) are key enzymes that
      catalyze the conversion of Cer to SM and GlcCer, respectively. GlcCer synthesis
      has been postulated to occur mainly in cis-Golgi, and SM synthesis is thought to
      occur in medial/trans-Golgi; however, SMS1 and GCS are known to partially co
      localize in cisternae, especially in medial/trans-Golgi. Here, we report that
      SMS1 and GCS can form a heteromeric complex, in which the N terminus of SMS1 and
      the C terminus of GCS are in close proximity. Deletion of the N-terminal sterile
      alpha-motif of SMS1 reduced the stability of the SMS1-GCS complex, resulting in a
      significant reduction in SM synthesis in vivo In contrast, chemical-induced
      heterodimerization augmented SMS1 activity, depending on an increase in the
      amount and stability of the complex. Fusion of the SMS1 N terminus to the GCS C
      terminus via linkers of different lengths increased SM synthesis and decreased
      GlcCer synthesis in vivo These results suggest that formation of the SMS1-GCS
      heteromeric complex increases SM synthesis and decreases GlcCer synthesis.
      Importantly, this regulation of relative Cer levels by the SMS1-GCS complex was
      confirmed by CRISPR/Cas9-mediated knockout of SMS1 or GCS combined with
      pharmacological inhibition of Cer transport protein in HEK293T cells. Our
      findings suggest that complex formation between SMS1 and GCS is part of a
      critical mechanism controlling the metabolic fate of Cer in the Golgi.

PMID- 30242130
TI  - The scaffolding protein ZO-1 coordinates actomyosin and epithelial apical
      specializations in vitro and in vivo.
AB  - Polarized epithelia assemble into sheets that compartmentalize organs and
      generate tissue barriers by integrating apical surfaces into a single, unified
      structure. This tissue organization is shared across organs, species, and
      developmental stages. The processes that regulate development and maintenance of
      apical epithelial surfaces are, however, undefined. Here, using an intestinal
      epithelial-specific knockout (KO) mouse and cultured epithelial cells, we show
      that the tight junction scaffolding protein zonula occludens-1 (ZO-1) is
      essential for development of unified apical surfaces in vivo and in vitro We
      found that U5 and GuK domains of ZO-1 are necessary for proper apical surface
      assembly, including organization of microvilli and cortical F-actin; however,
      direct interactions with F-actin through the ZO-1 actin-binding region (ABR) are
      not required. ZO-1 lacking the PDZ1 domain, which binds claudins, rescued apical
      structure in ZO-1-deficient epithelia, but not in cells lacking both ZO-1 and ZO
      2, suggesting that heterodimerization with ZO-2 restores PDZ1-dependent ZO-1
      interactions that are vital to apical surface organization. Pharmacologic F-actin
      disruption, myosin II motor inhibition, or dynamin inactivation restored apical
      epithelial structure in vitro and in vivo, indicating that ZO-1 directs
      epithelial organization by regulating actomyosin contraction and membrane
      traffic. We conclude that multiple ZO-1-mediated interactions contribute to
      coordination of epithelial actomyosin function and genesis of unified apical
      surfaces.

PMID- 30242131
TI  - Direct observation of conformational dynamics of the PH domain in phospholipases
      Cepsilon and beta may contribute to subfamily-specific roles in regulation.
AB  - Phospholipase C (PLC) enzymes produce second messengers that increase the
      intracellular Ca2+ concentration and activate protein kinase C (PKC). These
      enzymes also share a highly conserved arrangement of core domains. However, the
      contributions of the individual domains to regulation are poorly understood,
      particularly in isoforms lacking high-resolution information, such as PLCepsilon.
      Here, we used small-angle X-ray scattering (SAXS), EM, and functional assays to
      gain insights into the molecular architecture of PLCepsilon, revealing that its
      PH domain is conformationally dynamic and essential for activity. We further
      demonstrate that the PH domain of PLCbeta exhibits similar dynamics in solution
      that are substantially different from its conformation observed in multiple
      previously reported crystal structures. We propose that this conformational
      heterogeneity contributes to subfamily-specific differences in activity and
      regulation by extracellular signals.

PMID- 30242132
TI  - Movement kinematics drive chain selection toward intention detection.
AB  - The ability to understand intentions based on another's movements is crucial for
      human interaction. This ability has been ascribed to the so-called motor chaining
      mechanism: anytime a motor chain is activated (e.g., grasp-to-drink), the
      observer attributes to the agent the corresponding intention (i.e., to drink)
      from the first motor act (i.e., the grasp). However, the mechanisms by which a
      specific chain is selected in the observer remain poorly understood. In the
      current study, we investigate the possibility that in the absence of
      discriminative contextual cues, slight kinematic variations in the observed grasp
      inform mapping to the most probable chain. Chaining of motor acts predicts that,
      in a sequential grasping task (e.g., grasp-to-drink), electromyographic (EMG)
      components that are required for the final act [e.g., the mouth-opening mylohyoid
      (MH) muscle] show anticipatory activation. To test this prediction, we used MH
      EMG, transcranial magnetic stimulation (TMS; MH motor-evoked potentials), and
      predictive models of movement kinematics to measure the level and timing of MH
      activation during the execution (Experiment 1) and the observation (Experiment 2)
      of reach-to-grasp actions. We found that MH-related corticobulbar excitability
      during grasping observation varied as a function of the goal (to drink or to
      pour) and the kinematics of the observed grasp. These results show that subtle
      changes in movement kinematics drive the selection of the most probable motor
      chain, allowing the observer to link an observed act to the agent's intention.

PMID- 30242136
TI  - On the use of group performance and rights for environmental protection and
      resource management.
AB  - Environmental and natural resource (ENR) policies that focus on group outcomes
      are common but have received relatively less attention from economists than
      policies based on individual behavior. Existing research tends to focus on
      particular contexts, such as water or air quality, fisheries, or land use. This
      paper discusses unifying themes of group performance policies, along with their
      advantages and disadvantages. We discuss a range of specific policy instruments,
      including group-based taxes, subsidies, and fixed penalties. We show how, in
      principle, group-based policies can be designed to achieve efficient provision of
      group-level environmental performance; however, in some cases, group policies can
      lead to suboptimal outcomes. We discuss the incentives for collaboration that can
      arise when regulators impose group performance policies, and the role that it can
      play in promoting efficient outcomes. We argue that the success of group-based
      policies will depend both on how the policy is designed (i.e., the external
      rewards and penalties) and on how the group operates. This implies potential
      complementarities between "top-down" regulatory interventions based on group
      performance and "bottom-up" within-group incentives for self-governance. Our
      discussion suggests that group performance policies should play a more prominent
      role in the suite of policy instruments considered by scholars and policymakers
      concerned with ENR management.

PMID- 30242133
TI  - Activation of autophagy rescues synaptic and cognitive deficits in fragile X
      mice.
AB  - Fragile X syndrome (FXS) is the most frequent form of heritable intellectual
      disability and autism. Fragile X (Fmr1-KO) mice exhibit aberrant dendritic spine
      structure, synaptic plasticity, and cognition. Autophagy is a catabolic process
      of programmed degradation and recycling of proteins and cellular components via
      the lysosomal pathway. However, a role for autophagy in the pathophysiology of
      FXS is, as yet, unclear. Here we show that autophagic flux, a functional readout
      of autophagy, and biochemical markers of autophagy are down-regulated in
      hippocampal neurons of fragile X mice. We further show that enhanced activity of
      mammalian target of rapamycin complex 1 (mTORC1) and translocation of Raptor, a
      defining component of mTORC1, to the lysosome are causally related to reduced
      autophagy. Activation of autophagy by delivery of shRNA to Raptor directly into
      the CA1 of living mice via the lentivirus expression system largely corrects
      aberrant spine structure, synaptic plasticity, and cognition in fragile X mice.
      Postsynaptic density protein (PSD-95) and activity-regulated cytoskeletal
      associated protein (Arc/Arg3.1), proteins implicated in spine structure and
      synaptic plasticity, respectively, are elevated in neurons lacking fragile X
      mental retardation protein. Activation of autophagy corrects PSD-95 and Arc
      abundance, identifying a potential mechanism by which impaired autophagy is
      causally related to the fragile X phenotype and revealing a previously
      unappreciated role for autophagy in the synaptic and cognitive deficits
      associated with fragile X syndrome.

PMID- 30242137
TI  - First-principles-based reaction kinetics from reactive molecular dynamics
      simulations: Application to hydrogen peroxide decomposition.
AB  - This paper presents our vision of how to use in silico approaches to extract the
      reaction mechanisms and kinetic parameters for complex condensed-phase chemical
      processes that underlie important technologies ranging from combustion to
      chemical vapor deposition. The goal is to provide an analytic description of the
      detailed evolution of a complex chemical system from reactants through various
      intermediates to products, so that one could optimize the efficiency of the
      reactive processes to produce the desired products and avoid unwanted side
      products. We could start with quantum mechanics (QM) to ensure an accurate
      description; however, to obtain useful kinetics we need to average over ~10-nm
      spatial scales for ~1 ns, which is prohibitively impractical with QM. Instead, we
      use the reactive force field (ReaxFF) trained to fit QM to carry out the reactive
      molecular dynamics (RMD). We focus here on showing that it is practical to
      extract from such RMD the reaction mechanisms and kinetics information needed to
      describe the reactions analytically. This analytic description can then be used
      to incorporate the correct reaction chemistry from the QM/ReaxFF atomistic
      description into larger-scale simulations of ~10 nm to micrometers to millimeters
      to meters using analytic approaches of computational fluid dynamics and/or
      continuum chemical dynamics. In the paper we lay out the strategy to extract the
      mechanisms and rate parameters automatically without the necessity of knowing any
      details of the chemistry. We consider this to be a proof of concept. We refer to
      the process as RMD2Kin (reactive molecular dynamics to kinetics) for the general
      approach and as ReaxMD2Kin (ReaxFF molecular dynamics to kinetics) for QM-ReaxFF
      based reaction kinetics.

PMID- 30242138
TI  - Fourteen-year-old boy with decreased appetite and pedal swelling.
AB  - : CLINICAL INTRODUCTION: A 14-year-old boy presented with history of decreased
      appetite and bilateral swelling of feet for 6 months. He did not give any
      associated history of orthopnoea or paroxysmal nocturnal dyspnoea. He was born by
      a normal delivery after a non-consanguineous marriage. He had an unremarkable
      birth and childhood health history. There was no family history of significant
      cardiovascular illness or sudden death. Clinical examination showed an average
      built boy with elevated jugular venous pressure with prominent v wave and
      bilateral pitting pedal oedema. Cardiovascular examination showed normal first
      (S1) and second (S2) heart sounds and a short early systolic murmur over
      tricuspid region. Other systems examination was remarkable for soft tender
      hepatomegaly.ECG showed sinus rhythm with tall, peaked p waves. Chest X-ray
      revealed enlargement along the right cardiac border. Transthoracic
      echocardiographic images are shown in figure 1A (apical four-chamber view) and
      figure 1B (tricuspid inflow Doppler). There was no colour Doppler evidence of
      interatrial shunt. QUESTION: What is the most likely diagnosis of his
      condition?Endomyocardial fibrosis (EMF)Ebstein's anomalyArrhythmogenic right
      ventricular dysplasia (ARVD)Idiopathic dilatation of right atriumRestrictive
      cardiomyopathy.

PMID- 30242135
TI  - Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B promotes
      breast cancer stem cell enrichment.
AB  - Breast cancer stem cells (BCSCs), which are characterized by a capacity for
      unlimited self-renewal and for generation of the bulk cancer cell population,
      play a critical role in cancer relapse and metastasis. Hypoxia is a common
      feature of the cancer microenvironment that stimulates the specification and
      maintenance of BCSCs. In this study, we found that hypoxia increased expression
      of adenosine receptor 2B (A2BR) in human breast cancer cells through the
      transcriptional activity of hypoxia-inducible factor 1. The binding of adenosine
      to A2BR promoted BCSC enrichment by activating protein kinase C-delta, which
      phosphorylated and activated the transcription factor STAT3, leading to increased
      expression of interleukin 6 and NANOG, two key mediators of the BCSC phenotype.
      Genetic or pharmacological inhibition of A2BR expression or activity decreased
      hypoxia- or adenosine-induced BCSC enrichment in vitro, and dramatically impaired
      tumor initiation and lung metastasis after implantation of MDA-MB-231 human
      breast cancer cells into the mammary fat pad of immunodeficient mice. These data
      provide evidence that targeting A2BR might be an effective strategy to eradicate
      BCSCs.

PMID- 30242139
TI  - Influence of myocardial scar on the response to frequent premature ventricular
      complex ablation.
AB  - OBJECTIVE: This study aims to evaluate the influence of myocardial scar after
      premature ventricular complexes (PVC) ablation in patients with left ventricular
      (LV) dysfunction. METHODS: 70 consecutive patients (58+/-11 years, 58 (83%) men,
      23% (18-32) mean PVC burden) with LV dysfunction and frequent PVCs submitted for
      ablation were included. A late gadolinium enhancement cardiac magnetic resonance
      (LGE-CMR) was performed prior to the ablation and a quantitative and qualitative
      analysis of the scar was done. RESULTS: Left ventricular ejection fraction
      progressively improved from 34.3%+/-9% at baseline to 44.4%+/-12% at 12 months
      (p<0.01) and 48 (69%) patients were echocardiographic responders. New York Heart
      Association class improved from 1.96+/-0.9 points at baseline to 1.36+/-0.6 at 12
      months (p<0.001). Brain natriuretic peptide decreased from 120 (60-284) to 46 (23
      81) pg/mL (p=0.04). Twenty-nine (41%) patients showed scar in the preprocedural
      LGE-CMR with a mean scar mass of 10.4 (5-20) g. Mean scar mass was significantly
      smaller in responders than in non-responders (0 (0-4.7) g vs 2 (0-14) g,
      respectively, p=0.017). PVC burden reduction (OR 1.09 (1.01-1.16), p=0.02) and
      scar mass (OR 0.9 (0.81-0.99), p=0.04) were independent predictors of response,
      but the former showed a higher accuracy. CONCLUSIONS: Presence of myocardial scar
      modulates, but does not preclude, the probability of response to PVC ablation in
      patients with LV dysfunction.

PMID- 30242134
TI  - ASTN2 modulates synaptic strength by trafficking and degradation of surface
      proteins.
AB  - Surface protein dynamics dictate synaptic connectivity and function in neuronal
      circuits. ASTN2, a gene disrupted by copy number variations (CNVs) in
      neurodevelopmental disorders, including autism spectrum, was previously shown to
      regulate the surface expression of ASTN1 in glial-guided neuronal migration.
      Here, we demonstrate that ASTN2 binds to and regulates the surface expression of
      multiple synaptic proteins in postmigratory neurons by endocytosis, resulting in
      modulation of synaptic activity. In cerebellar Purkinje cells (PCs), by
      immunogold electron microscopy, ASTN2 localizes primarily to endocytic and
      autophagocytic vesicles in the cell soma and in subsets of dendritic spines.
      Overexpression of ASTN2 in PCs, but not of ASTN2 lacking the FNIII domain,
      recurrently disrupted by CNVs in patients, including in a family presented here,
      increases inhibitory and excitatory postsynaptic activity and reduces levels of
      ASTN2 binding partners. Our data suggest a fundamental role for ASTN2 in dynamic
      regulation of surface proteins by endocytic trafficking and protein degradation.

PMID- 30242140
TI  - Birth weight in pregnancies complicated by maternal heart disease.
AB  - OBJECTIVE: To assess median and percentile birthweight distribution in women with
      various groups of heart disease relative to a contemporaneous comparison group.
      METHODS: Data on birth weight and gestational age were collected from 1321
      pregnancies >=24 weeks' gestation in 1053 women with heart disease from seven UK
      maternity units. Women were assigned to one of 16 groups according to their
      cardiac lesion. In units where it was possible, data on two births, one
      delivering before and one after index cases, were collected, giving 2307
      comparators. Birthweight percentiles (corrected for gestational age, sex and
      parity) were calculated using Aberdeen norms. We assessed the association of
      birth weight with cardiac lesion, maternal hypoxaemia (saturations <90%),
      systemic ventricular function and beta-blockers. RESULTS: 1321 pregnancies in
      women with heart disease and 2307 comparators were studied. Almost all groups
      with heart disease had lower median and percentile birth weights than
      comparators, significantly in 10 groups, the biggest effect seen in women with
      Fontan circulation, pulmonary hypertension, prosthetic heart valves, systemic
      right ventricle, Marfan syndrome, repaired tetralogy of Fallot and cardiomyopathy
      (in that order). In 307 pregnancies, women took beta-blockers; median birth
      weight adjusted for maternal age, parity and the effect of the cardiac lesion was
      3116.7 g (IQR 790.4) when beta-blockers were used and 3354.3 g (IQR 634.1) when
      they were not (p<0.001). 17 women had saturations <90%, and median birth weight
      was significantly lower, 3105.4 g (IQR 1288.9) versus 3387.7 g (IQR 729.8)
      (p=0.006). CONCLUSION: Our findings identify specific groups of women with heart
      disease at risk of having a small baby.

PMID- 30242141
TI  - Mitral valve prolapse and sudden cardiac death: a systematic review and meta
      analysis.
AB  - OBJECTIVES: Mitral valve prolapse (MVP) is commonly observed as a benign finding.
      However, the literature suggests that it may be associated with sudden cardiac
      death (SCD). We performed a meta-analysis and systematic review to determine the:
      (1) prevalence of MVP in the general population; (2) prevalence of MVP in all SCD
      and unexplained SCD; (3) incidence of SCD in MVP and (4) risk factors for SCD.
      METHODS: The English medical literature was searched for: (1) MVP community
      prevalence; (2) MVP prevalence in SCD cohorts; (3) incidence SCD in MVP and (4)
      SCD risk factors in MVP. Thirty-four studies were identified for inclusion. This
      study was registered with PROSPERO (CRD42018089502). RESULTS: The prevalence of
      MVP was 1.2% (95% CI 0.5 to 2.0) in community populations. Among SCD victims, the
      cause of death remained undetermined in 22.1% (95% CI 13.4 to 30.7); of these,
      MVP was observed in 11.7% (95% CI 5.8 to 19.1). The incidence of SCD in the MVP
      population was 0.14% (95% CI 0.1 to 0.3) per year. Potential risk factors for SCD
      include bileaflet prolapse, ventricular fibrosis complex ventricular ectopy and
      ST-T wave abnormalities. CONCLUSION: The high prevalence of MVP in cohorts of
      unexplained SCD despite low population prevalence provides indirect evidence of
      an association of MVP with SCD. The absolute number of people exposed to the risk
      of SCD is significant, although the incidence of life-threatening arrhythmic
      events in the general MVP population remains low. High-risk features include
      bileaflet prolapse, ventricular fibrosis, ST-T wave abnormalities and frequent
      complex ventricular ectopy. TRIAL REGISTRATION: PROSPERO (CRD42018089502).

PMID- 30242142
TI  - Percutaneous coronary intervention for stable coronary artery disease.
AB  - The adverse consequences of stable coronary artery disease (CAD) are death,
      myocardial infarction (MI) and angina. Trials in stable CAD show that
      percutaneous coronary intervention (PCI) does not reduce mortality. PCI does
      appear to reduce spontaneous MI rates but at the expense of causing some
      periprocedural MI. Therefore, the main purpose of PCI is to relieve angina.
      Indeed, patients and physicians often choose PCI rather than first attempting to
      control symptoms with anti-anginal medications as recommended by guidelines.
      Nevertheless, it is unclear how effective PCI is at relieving angina. This is
      because, whereas anti-anginal medications are universally required to be tested
      against placebo, there is no such requirement for procedural interventions such
      as PCI. The first placebo-controlled trial of PCI showed a surprisingly small
      effect size. This may be because it is overly simplistic to assume that the
      presence of a stenosis and inducible ischaemia in a patient means that the
      clinical chest pain they report is caused by ischaemia. In this article, we
      review the evidence base and argue that if we as a medical specialty wish to lead
      the science of procedures for symptom control, we should recognise the special
      merit of placebo-controlled experiments.

PMID- 30242143
TI  - Prevalence and correlates of and a risk score to identify asymptomatic anorectal
      gonorrhoea and chlamydia infection among men who have sex with men in Kisumu,
      Kenya.
AB  - OBJECTIVES: In settings where laboratory capacity is limited, the WHO recommends
      presumptive treatment for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis
      (CT) in asymptomatic men who have sex with men (MSM) at high risk for these
      infections. However, little is known about how best to target this intervention.
      We aimed to identify correlates of anorectal NG/CT infection in Kenyan MSM with
      and without anorectal symptoms and evaluate the performance of an empirical,
      model-based risk score to identify cases in asymptomatic men. METHODS: Anorectal
      NG/CT infections were diagnosed by the Abbott RealTime NG/CT nucleic acid
      amplification testamong 698 MSM at enrolment into the Anza Mapema study.
      Multivariable logistic regression was used to identify correlates of anorectal
      NG/CT infection in men with and without anorectal symptoms. Using coefficients
      from the final multivariable model for asymptomatic men, we calculated a risk
      score for each participant. Risk score performance was determined by calculating
      the sensitivity, specificity and number needed to treat (NNT) to identify one
      NG/CT infection. RESULTS: Overall anorectal NG/CT infection prevalence was 5.2%
      (n=36), of which 58.3% (n=21) were asymptomatic. Factors associated with
      anorectal NG/CT infection in asymptomatic men were aged 18-24 years (aOR=7.6; 95%
      CI: 1.7 to 33.2), HIV positive serostatus (aOR=6.9; 95% CI: 2.2 to 21.6) and
      unprotected anal sex in the past 3 months (aOR=3.8; 95% CI: 1.2 to 11.9).
      Sensitivity and specificity were optimal (81.0% and 66.1%, respectively) at a
      model-derived risk score cut-point >=3, and the NNT was 12. CONCLUSIONS: A model
      derived risk score based on correlates of anorectal NG/CT infection in
      asymptomatic participants would be sensitive and efficient (i.e, low NNT) for
      targeting presumptive treatment. If validated in other settings, this risk score
      could improve on the WHO algorithm and help reduce the burden of asymptomatic
      anorectal NG/CT infections among MSM in settings where diagnostic testing is not
      available.

PMID- 30242144
TI  - Expression of B Cell-Specific Moloney Murine Leukemia Virus Integration Site 1
      (BMI-1) and WW Domain-Containing Oxidoreductase (WWOX) in Liver Cancer Tissue and
      Normal Liver Tissue.
AB  - BACKGROUND The aim of this study was to compare the expression levels of mRNA of
      the B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) and
      the WW domain-containing oxidoreductase (WWOX) genes and their protein products
      in tissues from patients with liver cancer with normal liver tissues from
      patients without liver cancer. MATERIAL AND METHODS The liver cancer group (N=56)
      included patients with available tissue samples of histologically confirmed liver
      cancer. The control group (N=24) included histologically confirmed normal liver
      tissue samples. Immunofluorescence staining and Western blot were used to detect
      and compare protein expression of Bmi-1 and WWOX in liver tissues in the liver
      cancer group and the control group. Reverse transcription-polymerase chain
      reaction (RT-PCR) was used to detect and compare mRNA expression of BMI-1 and
      WWOX in liver tissues in the liver cancer group and the control group. Expression
      levels of the protein and mRNA levels and the clinicopathological features
      including patient prognosis in liver cancer were evaluated statistically using
      analysis of variance (ANOVA). RESULTS There were significant differences in the
      expression levels of protein and mRNA of BMI-1 and WWOX between the liver cancer
      group and the control group. BMI-1 mRNA and protein expression were significantly
      increased, and WWOX mRNA and protein expression were significantly reduced in
      liver cancer tissue, compared with normal liver tissue (p<0.05). CONCLUSIONS In
      liver cancer tissue compared with normal liver, the expression of BMI-1 and WWOX
      mRNA and their protein products were upregulated and down-regulated,
      respectively.

PMID- 30242146
TI  - Cholinergic basal forebrain neurons regulate fear extinction consolidation
      through p75 neurotrophin receptor signaling.
AB  - Cholinergic basal forebrain (cBF)-derived neurotransmission plays a crucial role
      in regulating neuronal function throughout the cortex, yet the mechanisms
      controlling cholinergic innervation to downstream targets have not been
      elucidated. Here we report that removing the p75 neurotrophin receptor (p75NTR)
      from cBF neurons induces a significant impairment in fear extinction
      consolidation. We demonstrate that this is achieved through alterations in
      synaptic connectivity and functional activity within the medial prefrontal
      cortex. These deficits revert back to wild-type levels upon re-expression of the
      active domain of p75NTR in adult animals. These findings demonstrate a novel role
      for cholinergic neurons in fear extinction consolidation and suggest that
      neurotrophic signaling is a key regulator of cholinergic-cortical innervation and
      function.

PMID- 30242147
TI  - Notch ligand Jagged1 promotes mesenchymal stromal cell-based cartilage repair.
AB  - Placenta-derived mesenchymal stromal cells (PMSCs) provide a promising cell
      source for tissue regeneration. However, rapid induction of PMSC chondrogenic
      differentiation during therapeutic transplantation remains extremely challenging.
      Here we undertook a study to determine if Notch inhibition by soluble Jagged1
      (JAG1) peptides could be utilized to accelerate PMSC-induced cartilage
      regeneration in a mouse post-traumatic osteoarthritis (PTOA) model. Our results
      showed that treatment of PMSCs with soluble JAG1 significantly enhanced
      chondrogenesis in culture as shown by increased alcian blue staining and
      decreased Notch target Hes1 expression when compared to those in lgG-treated
      control cells. Importantly, significantly enhanced cartilage formation and
      decreased joint inflammation were observed when JAG1-treated PMSCs were injected
      into mouse PTOA knee joints. Finally, in vivo cell tracing showed that more JAG1
      treated PMSCs remained in knee joint tissues and that JAG1-treated PMSCs
      exhibited greater PMSC chondrogenic differentiation than lgG-treated control
      PMSCs at 4 weeks after injection. These data indicate that transient Notch
      inhibition by soluble JAG1 could be used to enhance PMSC survival and
      chondrogenic differentiation, thereby increasing the therapeutic potential of
      PMSCs for cartilage regeneration.

PMID- 30242145
TI  - The implications of signaling lipids in cancer metastasis.
AB  - Metastasis is the most malignant stage of cancer. Lipid metabolic abnormalities
      are now increasingly recognized as characteristics of cancer cells. The
      accumulation of certain lipid species, such as signaling lipids, due to the
      avidity of lipid metabolism may be a causal factor of tumor malignant progression
      and metastatic behavior. In this review, we first describe signaling lipids
      implicated in cancer migration, invasion and metastasis. Next, we summarize the
      regulatory signaling hubs of lipid anabolic and catabolic metabolism. We then
      address lipid-rich circulating tumor cells (CTCs) and the lipid composition of
      exosomes budded off from tumor cells. We also present advances in targeting the
      regulatory hubs of lipid metabolism and signaling lipids in cancer therapy. Given
      the complexity of metabolic disorders in cancer, the development of significant
      portfolios of approaches to target signaling lipids by the integration of
      multiple chemical modulations, as well as molecular imaging modalities, should
      offer promising strategies for cancer therapy.

PMID- 30242148
TI  - Gap junction protein Connexin-43 is a direct transcriptional regulator of N
      cadherin in vivo.
AB  - Connexins are the primary components of gap junctions, providing direct links
      between cells under many physiological processes. Here, we demonstrate that in
      addition to this canonical role, Connexins act as transcriptional regulators. We
      show that Connexin 43 (Cx43) controls neural crest cell migration in vivo by
      directly regulating N-cadherin transcription. This activity requires interaction
      between Cx43 carboxy tail and the basic transcription factor-3, which drives the
      translocation of Cx43 tail to the nucleus. Once in the nucleus they form a
      complex with PolII which directly binds to the N-cadherin promoter. We found that
      this mechanism is conserved between amphibian and mammalian cells. Given the
      strong evolutionary conservation of connexins across vertebrates, this may
      reflect a common mechanism of gene regulation by a protein whose function was
      previously ascribed only to gap junctional communication.

PMID- 30242150
TI  - Forward models demonstrate that repetition suppression is best modelled by local
      neural scaling.
AB  - Inferring neural mechanisms from functional magnetic resonance imaging (fMRI) is
      challenging because the fMRI signal integrates over millions of neurons. One
      approach is to compare computational models that map neural activity to fMRI
      responses, to see which best predicts fMRI data. We use this approach to compare
      four possible neural mechanisms of fMRI adaptation to repeated stimuli (scaling,
      sharpening, repulsive shifting and attractive shifting), acting across three
      domains (global, local and remote). Six features of fMRI repetition effects are
      identified, both univariate and multivariate, from two independent fMRI
      experiments. After searching over parameter values, only the local scaling model
      can simultaneously fit all data features from both experiments. Thus fMRI
      stimulus repetition effects are best captured by down-scaling neuronal tuning
      curves in proportion to the difference between the stimulus and neuronal
      preference. These results emphasise the importance of formal modelling for
      bridging neuronal and fMRI levels of investigation.

PMID- 30242149
TI  - A naturally protective epitope of limited variability as an influenza vaccine
      target.
AB  - Current antigenic targets for influenza vaccine development are either highly
      immunogenic epitopes of high variability or conserved epitopes of low
      immunogenicity. This requires continuous update of the variable epitopes in the
      vaccine formulation or boosting of immunity to invariant epitopes of low natural
      efficacy. Here we identify a highly immunogenic epitope of limited variability in
      the head domain of the H1 haemagglutinin protein. We show that a cohort of young
      children exhibit natural immunity to a set of historical influenza strains which
      they could not have previously encountered and that this is partially mediated
      through the epitope. Furthermore, vaccinating mice with these epitope
      conformations can induce immunity to human H1N1 influenza strains that have
      circulated since 1918. The identification of epitopes of limited variability
      offers a mechanism by which a universal influenza vaccine can be created; these
      vaccines would also have the potential to protect against newly emerging
      influenza strains.

PMID- 30242152
TI  - Towards synthetic cells using peptide-based reaction compartments.
AB  - Membrane compartmentalization and growth are central aspects of living cells, and
      are thus encoded in every cell's genome. For the creation of artificial cellular
      systems, genetic information and production of membrane building blocks will need
      to be coupled in a similar manner. However, natural biochemical reaction networks
      and membrane building blocks are notoriously difficult to implement in vitro.
      Here, we utilized amphiphilic elastin-like peptides (ELP) to create self
      assembled vesicular structures of about 200 nm diameter. In order to genetically
      encode the growth of these vesicles, we encapsulate a cell-free transcription
      translation system together with the DNA template inside the peptide vesicles. We
      show in vesiculo production of a functioning fluorescent RNA aptamer and a
      fluorescent protein. Furthermore, we implement in situ expression of the membrane
      peptide itself and finally demonstrate autonomous vesicle growth due to the
      incorporation of this ELP into the membrane.

PMID- 30242151
TI  - A cocoon silk chemistry strategy to ultrathin N-doped carbon nanosheet with metal
      single-site catalysts.
AB  - Development of single-site catalysts supported by ultrathin two-dimensional (2D)
      porous matrix with ultrahigh surface area is highly desired but also challenging.
      Here we report a cocoon silk chemistry strategy to synthesize isolated metal
      single-site catalysts embedded in ultrathin 2D porous N-doped carbon nanosheets
      (M-ISA/CNS, M = Fe, Co, Ni). X-ray absorption fine structure analysis and
      spherical aberration correction electron microscopy demonstrate an atomic
      dispersion of metal atoms on N-doped carbon matrix. In particular, the Co-ISA/CNS
      exhibit ultrahigh specific surface area (2105 m2 g-1) and high activity for C-H
      bond activation in the direct catalytic oxidation of benzene to phenol with
      hydrogen peroxide at room temperature, while the Co species in the form of
      phthalocyanine and metal nanoparticle show a negligible activity. Density
      functional theory calculations discover that the generated O = Co = O center
      intermediates on the single Co sites are responsible for the high activity of
      benzene oxidation to phenol.

PMID- 30242153
TI  - Discovering human diabetes-risk gene function with genetics and physiological
      assays.
AB  - Developing systems to identify the cell type-specific functions regulated by
      genes linked to type 2 diabetes (T2D) risk could transform our understanding of
      the genetic basis of this disease. However, in vivo systems for efficiently
      discovering T2D risk gene functions relevant to human cells are currently
      lacking. Here we describe powerful interdisciplinary approaches combining
      Drosophila genetics and physiology with human islet biology to address this
      fundamental gap in diabetes research. We identify Drosophila orthologs of T2D
      risk genes that regulate insulin output. With human islets, we perform genetic
      studies and identify cognate human T2D-risk genes that regulate human beta cell
      function. Loss of BCL11A, a transcriptional regulator, in primary human islet
      cells leads to enhanced insulin secretion. Gene expression profiling reveals
      BCL11A-dependent regulation of multiple genes involved in insulin exocytosis.
      Thus, genetic and physiological systems described here advance the capacity to
      identify cell-specific T2D risk gene functions.

PMID- 30242154
TI  - A conformational sensor based on genetic code expansion reveals an autocatalytic
      component in EGFR activation.
AB  - Epidermal growth factor receptor (EGFR) activation by growth factors (GFs) relies
      on dimerization and allosteric activation of its intrinsic kinase activity,
      resulting in trans-phosphorylation of tyrosines on its C-terminal tail. While
      structural and biochemical studies identified this EGF-induced allosteric
      activation, imaging collective EGFR activation in cells and molecular dynamics
      simulations pointed at additional catalytic EGFR activation mechanisms. To gain
      more insight into EGFR activation mechanisms in living cells, we develop a
      Forster resonance energy transfer (FRET)-based conformational EGFR indicator
      (CONEGI) using genetic code expansion that reports on conformational transitions
      in the EGFR activation loop. Comparing conformational transitions, self
      association and auto-phosphorylation of CONEGI and its Y845F mutant reveals that
      Y845 phosphorylation induces a catalytically active conformation in EGFR
      monomers. This conformational transition depends on EGFR kinase activity and auto
      phosphorylation on its C-terminal tail, generating a looped causality that leads
      to autocatalytic amplification of EGFR phosphorylation at low EGF dose.

PMID- 30242157
TI  - Controlling factor of incoming plate hydration at the north-western Pacific
      margin.
AB  - Hydration of the subducting oceanic plate determines the amount of water
      transported from Earth's surface into its interior, and plate bending-related
      faulting (bend faulting) just prior to subduction is considered to promote
      hydration. Bend faulting shows significant spatial variation, but its
      contribution to hydration is still poorly understood. Here we present the results
      of controlled-source seismic surveys around the junction of the Japan and Kuril
      trenches. We found structural changes caused by bend faulting before subduction
      differed distinctly between both trenches and were well correlated with plate
      hydration after subduction, suggesting the bend faulting controls spatial
      variations in plate hydration. Differences in bend faulting are closely related
      to the angle between the current trench and the ancient spreading ridge, and the
      hydration is more extensive where this trench-ridge angle is oblique in the study
      area. Thus, we propose this angle is a major factor controlling plate hydration.

PMID- 30242155
TI  - Structures of insect Imp-L2 suggest an alternative strategy for regulating the
      bioavailability of insulin-like hormones.
AB  - The insulin/insulin-like growth factor signalling axis is an evolutionary ancient
      and highly conserved hormonal system involved in the regulation of metabolism,
      growth and lifespan in animals. Human insulin is stored in the pancreas, while
      insulin-like growth factor-1 (IGF-1) is maintained in blood in complexes with IGF
      binding proteins (IGFBP1-6). Insect insulin-like polypeptide binding proteins
      (IBPs) have been considered as IGFBP-like structural and functional homologues.
      Here, we report structures of the Drosophila IBP Imp-L2 in its free form and
      bound to Drosophila insulin-like peptide 5 and human IGF-1. Imp-L2 contains two
      immunoglobulin-like fold domains and its architecture is unrelated to human
      IGFBPs, suggesting a distinct strategy for bioavailability regulation of insulin
      like hormones. Similar hormone binding modes may exist in other insect vectors,
      as the IBP sequences are highly conserved. Therefore, these findings may open
      research routes towards a rational interference of transmission of diseases such
      as malaria, dengue and yellow fevers.

PMID- 30242156
TI  - Repeated inversions within a pannier intron drive diversification of
      intraspecific colour patterns of ladybird beetles.
AB  - How genetic information is modified to generate phenotypic variation within a
      species is one of the central questions in evolutionary biology. Here we focus on
      the striking intraspecific diversity of >200 aposematic elytral (forewing) colour
      patterns of the multicoloured Asian ladybird beetle, Harmonia axyridis, which is
      regulated by a tightly linked genetic locus h. Our loss-of-function analyses,
      genetic association studies, de novo genome assemblies, and gene expression data
      reveal that the GATA transcription factor gene pannier is the major regulatory
      gene located at the h locus, and suggest that repeated inversions and cis
      regulatory modifications at pannier led to the expansion of colour pattern
      variation in H. axyridis. Moreover, we show that the colour-patterning function
      of pannier is conserved in the seven-spotted ladybird beetle, Coccinella
      septempunctata, suggesting that H. axyridis' extraordinary intraspecific
      variation may have arisen from ancient modifications in conserved elytral colour
      patterning mechanisms in ladybird beetles.

PMID- 30242158
TI  - Tunable colloid trajectories in nematic liquid crystals near wavy walls.
AB  - The ability to dictate the motion of microscopic objects is an important
      challenge in fields ranging from materials science to biology. Field-directed
      assembly drives microparticles along paths defined by energy gradients. Nematic
      liquid crystals, consisting of rod-like molecules, provide new opportunities in
      this domain. Deviations of nematic liquid crystal molecules from uniform
      orientation cost elastic energy, and such deviations can be molded by bounding
      vessel shape. Here, by placing a wavy wall in a nematic liquid crystal, we impose
      alternating splay and bend distortions, and define a smoothly varying elastic
      energy field. A microparticle in this field displays a rich set of behaviors, as
      this system has multiple stable states, repulsive and attractive loci, and
      interaction strengths that can be tuned to allow reconfigurable states.
      Microparticles can transition between defect configurations, move along distinct
      paths, and select sites for preferred docking. Such tailored landscapes have
      promise in reconfigurable systems and in microrobotics applications.

PMID- 30242159
TI  - Alpha-enolase regulates the malignant phenotype of pulmonary artery smooth muscle
      cells via the AMPK-Akt pathway.
AB  - The molecular mechanisms underlying the metabolic shift toward increased
      glycolysis observed in pulmonary artery smooth muscle cells (PASMC) during the
      pathogenesis of pulmonary arterial hypertension (PAH) are not fully understood.
      Here we show that the glycolytic enzyme alpha-enolase (ENO1) regulates the
      metabolic reprogramming and malignant phenotype of PASMC. We show that ENO1
      levels are elevated in patients with associated PAH and in animal models of
      hypoxic pulmonary hypertension (HPH). The silencing or inhibition of ENO1
      decreases PASMC proliferation and de-differentiation, and induces PASMC
      apoptosis, whereas the overexpression of ENO1 promotes a synthetic, de-
      differentiated, and apoptotic-resistant phenotype via the AMPK-Akt pathway. The
      suppression of ENO1 prevents the hypoxia-induced metabolic shift from
      mitochondrial respiration to glycolysis in PASMC. Finally, we find that
      pharmacological inhibition of ENO1 reverses HPH in mice and rats, suggesting ENO1
      as a regulator of pathogenic metabolic reprogramming in HPH.

PMID- 30242160
TI  - Colorectal Cancer Screening Participation Among Asian Americans Overall and
      Subgroups in an Integrated Health Care Setting with Organized Screening.
AB  - BACKGROUND: Screening reduces colorectal cancer deaths, but <50% of Asian
      Americans are screening up-to-date according to surveys, with variability across
      Asian subgroups. We examined colorectal cancer screening participation among
      Asian Americans overall and Asian subgroups in a large integrated health care
      system with organized screening. METHODS: Data were electronically accessed to
      characterize screening in 2016 for Asians overall and subgroups relative to the
      National Colorectal Cancer Roundtable target of >=80% screening and compared with
      non-Hispanic whites. Screening up-to-date was defined as a colonoscopy with 10
      years, a sigmoidoscopy within 5 years, or a fecal immunochemical test (FIT)
      completed in 2016. RESULTS: Among 436,398 patients, 69,826 (16.0%) were Asian, of
      whom 79.8% were screening up-to-date vs. 77.6% of non-Hispanic whites (p <
      0.001). Almost all subgroups met the 80% target: Chinese (83.3%), Vietnamese
      (82.4%), Korean (82.1%), other Asian (80.3%), Filipino (78.7%), Asian Indian
      (79.6%), and Japanese (79.0%). Among Asians overall and non-Hispanic whites,
      50.6% and 48.4% of members were up-to-date with screening by colonoscopy, and
      28.0% and 28.2% were up-to-date by FIT, respectively. Across Asian subgroups,
      colonoscopy most frequently accounting for being screening up-to-date (range:
      47.4-59.7%), followed by FIT (range: 21.6-31.5%). CONCLUSIONS: In an organized
      screening setting, there were minimal differences in screening participation
      among Asian subgroups and almost all met the 80% screening target, despite
      differences in language preference. Screening test type differences across
      subgroups suggest possible preferences in screening modality, which can inform
      future research into tailored education or outreach.

PMID- 30242161
TI  - A tissue-specific self-interacting chromatin domain forms independently of
      enhancer-promoter interactions.
AB  - Self-interacting chromatin domains encompass genes and their cis-regulatory
      elements; however, the three-dimensional form a domain takes, whether this relies
      on enhancer-promoter interactions, and the processes necessary to mediate the
      formation and maintenance of such domains, remain unclear. To examine these
      questions, here we use a combination of high-resolution chromosome conformation
      capture, a non-denaturing form of fluorescence in situ hybridisation and super
      resolution imaging to study a 70 kb domain encompassing the mouse alpha-globin
      regulatory locus. We show that this region forms an erythroid-specific,
      decompacted, self-interacting domain, delimited by frequently apposed
      CTCF/cohesin binding sites early in terminal erythroid differentiation, and does
      not require transcriptional elongation for maintenance of the domain structure.
      Formation of this domain does not rely on interactions between the alpha-globin
      genes and their major enhancers, suggesting a transcription-independent mechanism
      for establishment of the domain. However, absence of the major enhancers does
      alter internal domain interactions. Formation of a loop domain therefore appears
      to be a mechanistic process that occurs irrespective of the specific interactions
      within.

PMID- 30242163
TI  - Beaming random lasers with soliton control.
AB  - Random lasers are resonator-less light sources where feedback stems from
      recurrent scattering at the expense of spatial profile and directionality.
      Suitably-doped nematic liquid crystals can random lase when optically pumped near
      resonance(s); moreover, through molecular reorientation within the transparency
      region, they support self-guided optical spatial solitons, i.e., light-induced
      waveguides. Here, we synergistically combine solitons and collinear pumping in
      weakly scattering dye-doped nematic liquid crystals, whereby random lasing and
      self-confinement concur to beaming the emission, with several improved features:
      all-optical switching driven by a low-power input, laser directionality and
      smooth output profile with high-conversion efficiency, externally controlled
      angular steering. Such effects make soliton-assisted random lasers an outstanding
      route towards application-oriented random lasers.

PMID- 30242162
TI  - Complex strain evolution of polar and magnetic order in multiferroic BiFeO3 thin
      films.
AB  - Electric-field control of magnetism requires deterministic control of the
      magnetic order and understanding of the magnetoelectric coupling in multiferroics
      like BiFeO3 and EuTiO3. Despite this critical need, there are few studies on the
      strain evolution of magnetic order in BiFeO3 films. Here, in (110)-oriented
      BiFeO3 films, we reveal that while the polarization structure remains relatively
      unaffected, strain can continuously tune the orientation of the antiferromagnetic
      spin axis across a wide angular space, resulting in an unexpected deviation of
      the classical perpendicular relationship between the antiferromagnetic axis and
      the polarization. Calculations suggest that this evolution arises from a
      competition between the Dzyaloshinskii-Moriya interaction and single-ion
      anisotropy wherein the former dominates at small strains and the two are
      comparable at large strains. Finally, strong coupling between the BiFeO3 and the
      ferromagnet Co0.9Fe0.1 exists such that the magnetic anisotropy of the
      ferromagnet can be effectively controlled by engineering the orientation of the
      antiferromagnetic-spin axis.

PMID- 30242164
TI  - An interstellar synthesis of phosphorus oxoacids.
AB  - Phosphorus signifies an essential element in molecular biology, yet given the
      limited solubility of phosphates on early Earth, alternative sources like
      meteoritic phosphides have been proposed to incorporate phosphorus into
      biomolecules under prebiotic terrestrial conditions. Here, we report on a
      previously overlooked source of prebiotic phosphorus from interstellar phosphine
      (PH3) that produces key phosphorus oxoacids-phosphoric acid (H3PO4), phosphonic
      acid (H3PO3), and pyrophosphoric acid (H4P2O7)-in interstellar analog ices
      exposed to ionizing radiation at temperatures as low as 5 K. Since the processed
      material of molecular clouds eventually enters circumstellar disks and is
      partially incorporated into planetesimals like proto Earth, an understanding of
      the facile synthesis of oxoacids is essential to untangle the origin of water
      soluble prebiotic phosphorus compounds and how they might have been incorporated
      into organisms not only on Earth, but potentially in our universe as well.

PMID- 30242165
TI  - Architecture-Guided Fluid Flow Directs Renal Biomineralization.
AB  - Nephrocalcinosis often begins on a calcium phosphate deposit, at the tip of the
      medullo-papillary complex (MPC) known as Randall's plaque (RP). Contextualizing
      proximally observed biominerals within the MPC has led us to postulate a
      mechanobiological switch that can trigger interstitial biomineralization at the
      MPC tip, remote from the intratubular biominerals. Micro X-ray computed
      tomography scans of human MPCs correlated with transmission and scanning electron
      micrographs, and X-ray energy dispersive spectrometry demonstrated novel findings
      about anatomically-specific biominerals. An abundance of proximal intratubular
      biominerals were associated with emergence of distal interstitial RP. The
      fundamental architecture of the MPC and mineral densities at the proximal and
      distal locations of the MPC differed markedly. A predominance of plate-like
      minerals or radially oriented plate-like crystallites within spheroidal minerals
      in the proximal intratubular locations, and core-shell type crystallites within
      spheroidal minerals in distal interstitial locations were observed. Based on the
      MPC anatomic location of structure-specific biominerals, a biological switch
      within the mineral-free zone occurring between the proximal and distal locations
      is postulated. The "on" and "off" switch is dependent on changes in the pressure
      differential resulting from changes in tubule diameters; the "Venturi effect"
      changes the "circumferential strain" and culminates in interstitial crystal
      deposits in the distal tubule wall in response to proximal tubular obstruction.
      These distal interstitial mineralizations can emerge into the collecting system
      of the kidney linking nephrocalcinosis with nephrolithiasis.

PMID- 30242166
TI  - Essential Nucleoid Associated Protein mIHF (Rv1388) Controls Virulence and
      Housekeeping Genes in Mycobacterium tuberculosis.
AB  - Tight control of gene expression is crucial for Mycobacterium tuberculosis to
      adapt to the changing environments encountered when infecting or exiting human
      cells. While three nucleoid associated proteins (NAPs) EspR, HupB and Lsr2 have
      been investigated, the role of a fourth, the mycobacterial integration host
      factor (mIHF), remains elusive. Here, we report a multidisciplinary functional
      analysis that exploits a conditional mIHF mutant. Gene silencing was bactericidal
      and resulted in elongated cells devoid of septa, with only one nucleoid. ChIP
      sequencing identified 153 broad peaks distributed around the chromosome, which
      were often situated upstream of transcriptional start sites where EspR also
      bound. RNA-sequencing showed expression of 209 genes to be heavily affected upon
      mIHF depletion, including those for many tRNAs, DNA synthesis and virulence
      pathways. Consistent with NAP function, mIHF acts as a global regulator by
      directly and indirectly controlling genes required for pathogenesis and for
      housekeeping functions.

PMID- 30242167
TI  - Mitochondrial transcription factor A (TFAM) shapes metabolic and invasion gene
      signatures in melanoma.
AB  - Mitochondria are central key players in cell metabolism, and mitochondrial DNA
      (mtDNA) instability has been linked to metabolic changes that contribute to
      tumorigenesis and to increased expression of pro-tumorigenic genes. Here, we use
      melanoma cell lines and metastatic melanoma tumors to evaluate the effect of
      mtDNA alterations and the expression of the mtDNA packaging factor, TFAM, on
      energetic metabolism and pro-tumorigenic nuclear gene expression changes. We
      report a positive correlation between mtDNA copy number, glucose consumption, and
      ATP production in melanoma cell lines. Gene expression analysis reveals a down
      regulation of glycolytic enzymes in cell lines and an up-regulation of amino acid
      metabolism enzymes in melanoma tumors, suggesting that TFAM may shift melanoma
      fuel utilization from glycolysis towards amino acid metabolism, especially
      glutamine. Indeed, proliferation assays reveal that TFAM-down melanoma cell lines
      display a growth arrest in glutamine-free media, emphasizing that these cells
      rely more on glutamine metabolism than glycolysis. Finally, our data indicate
      that TFAM correlates to VEGF expression and may contribute to tumorigenesis by
      triggering a more invasive gene expression signature. Our findings contribute to
      the understanding of how TFAM affects melanoma cell metabolism, and they provide
      new insight into the mechanisms by which TFAM and mtDNA copy number influence
      melanoma tumorigenesis.

PMID- 30242168
TI  - A Microfluidic Fluorescent Flow Cytometry Capable of Quantifying Cell Sizes and
      Numbers of Specific Cytosolic Proteins.
AB  - This study presents a microfluidics based cytometry capable of characterizing
      cell sizes and counting numbers of specific cytosolic proteins where cells were
      first bound by antibodies labelled with fluorescence and then aspirated into a
      constriction microchannel in which fluorescent levels were measured. These raw
      fluorescent pulses were further divided into a rising domain, a stable domain and
      a declining domain. In addition, antibody solutions with labelled fluorescence
      were aspirated through the constriction microchannel, yielding curves to
      translate raw fluorescent levels to protein concentrations. By using key
      parameters of three domains as well as the calibration curves, cell diameters and
      the absolute number of beta-actins at the single-cell level were quantified as
      14.2 +/- 1.7 MUm and 9.62 +/- 4.29 * 105 (A549, ncell = 14 242), 13.0 +/- 2.0 MUm
      and 6.46 +/- 3.34 * 105 (Hep G2, ncell = 35 932), 13.8 +/- 1.9 MUm and 1.58 +/-
      0.90 * 106 (MCF 10 A, ncell = 16 650), and 12.7 +/- 1.5 MUm and 1.09 +/- 0.49 *
      106 (HeLa, ncell = 26 246). This platform could be further adopted to measure
      numbers of various cytosolic proteins, providing key insights in proteomics at
      the single-cell level.

PMID- 30242169
TI  - Stationary Computed Tomography for Space and other Resource-constrained
      Environments.
AB  - Computed tomography (CT) is used to diagnose many emergent medical conditions,
      including stroke and traumatic brain injuries. Unfortunately, the size, weight,
      and expense of CT systems make them largely inaccessible for patients outside of
      major hospitals. We have designed a module containing multiple miniature x-ray
      sources that could allow for CT systems to be significantly lighter, smaller, and
      cheaper, and to operate without any moving parts. We have developed a novel
      photocathode-based x-ray source, created by depositing a thin film of magnesium
      on an electron multiplier. When illuminated by a UV LED, this photocathode emits
      a beam of electrons, with a beam current of up to 1 mA. The produced electrons
      are accelerated through a high voltage to a tungsten target. These sources are
      individually addressable and can be pulsed rapidly, through electronic control of
      the LEDs. Seven of these sources are housed together in a 17.5 degree arc within
      a custom vacuum manifold. A full ring of these modules could be used for CT
      imaging. By pulsing the sources in series, we are able to demonstrate x-ray
      tomosynthesis without any moving parts. With a clinical flat-panel detector, we
      demonstrate 3D acquisition and reconstructions of a cadaver swine lung.

PMID- 30242170
TI  - Exceptional dinosaur fossils reveal early origin of avian-style digestion.
AB  - Birds have a highly specialized and efficient digestive system, but when this
      system originated remains uncertain. Here we report six gastric pellets
      attributable to the recently discovered 160-million-year-old troodontid dinosaur
      Anchiornis, which is among the key taxa for understanding the transition to
      birds. The gastric pellets contain lightly acid-etched lizard bones or fish
      scales, and some are associated with Anchiornis skeletons or even situated within
      the oesophagus. Anchiornis is the earliest and most basal theropod known to have
      produced gastric pellets. In combination with other lines of evidence, the
      pellets suggest that a digestive system resembling that of modern birds was
      already present in basal members of the Paraves, a clade including troodontids,
      dromaeosaurids, and birds, and that the evolution of modern avian digestion may
      have been related to the appearance of aerial locomotion in this lineage.

PMID- 30242171
TI  - Lagrangian-like Volume Tracking Paradigm for Mass, Momentum and Energy of
      Nearshore Tsunamis and Damping Mechanism.
AB  - There is a gap between model- or theory-based research outputs, which suggest
      that the runup and amplification of nonbreaking waves generally increase as the
      sea bottom slopes decrease, and field observations, which indicate that tsunami
      damage has been rarely reported in places with vast continental shelfs. To
      resolve this contradiction, we propose a Lagrangian-like volume tracking paradigm
      to describe the energy, mass, and momentum of travelling nearshore tsunamis and
      apply the paradigm to analyse the tsunami damping mechanism at typical
      geophysical scales. The results support the following conclusions: (i) The
      suggested paradigm is consistent with field observations; continental shelfs with
      long and mild slopes can effectively diminish tsunami impacts. (ii) Potential
      energy becomes significant due to the energy transformation process on steeply
      sloped bathymetries. (iii) On mild-sloped bathymetries, tsunami potential and
      kinetic energies are conserved until breaking occurs. After breaking, undular
      bores attenuate tsunami energies effectively. (iv) For extended continental shelf
      bathymetries, more of the tsunami mass is reflected offshore.

PMID- 30242173
TI  - Dvl3 polymorphism interacts with life events and pro-inflammatory cytokines to
      influence major depressive disorder susceptibility.
AB  - The purpose of this study is to explore Dvl3 variants and their interaction with
      negative life events on MDD susceptibility in a Chinese Han population.
      Additionally, we also attempted to identify whether there is an association
      between Dvl3 variants and pro-inflammatory cytokines. A total of 1102
      participants, consisting of 550 patients with MDD and 552 healthy subjects, were
      recruited for genotyping by TaqMan allelic discrimination assay. Pro-inflammatory
      cytokine mRNA levels in peripheral blood were measured by QPCR. After the
      assessment of negative life events by the Life Events Scale, the Dvl3 gene
      environment interaction (G * E) and risk factors were evaluated using generalized
      multifactor dimensionality reduction method (GMDR) and logistic regression
      analysis, respectively. This study is the first to reveal the interaction between
      Dvl3 allelic variations and negative life events as well as pro-inflammatory
      cytokines on MDD susceptibility in a Chinese Han population.

PMID- 30242172
TI  - The potential HLA Class I-restricted epitopes derived from LeIF and TSA of
      Leishmania donovani evoke anti-leishmania CD8+ T lymphocyte response.
AB  - To explore new protective measure against visceral leishmaniasis, reverse
      vaccinology approach was employed to identify key immunogenic regions which can
      mediate long-term immunity. In-depth computational analysis revealed nine
      promiscuous epitopes which can possibly be presented by 46 human leukocyte
      antigen, thereby broadening the worldwide population up to 94.16%. This is of
      reasonable significance that most of the epitopes shared 100% sequence homology
      with other Leishmania species and could evoke a common pattern of protective
      immune response. Transporter associated with antigen processing binding affinity,
      molecular docking approach followed by dynamics simulation and human leukocyte
      antigen stabilization assay suggested that the best five optimal set of epitopes
      bind in between alpha1 and alpha2 binding groove with sufficient affinity and
      stability which allows the translocation of intact epitope to the cell surface.
      Fascinatingly, the human leukocyte antigen stabilization assay exhibited a modest
      correlation with the positive immunogenicity score predicted by class I pMHC
      immunogenicity predictor. A support for this notion came from ELISA and FACS
      analysis where the epitopes as a cocktail induced CD8+ IFN-gamma and Granzyme B
      levels significantly in treated visceral leishmaniasis subject which suggests the
      immunogenic ability of the selected epitopes.

PMID- 30242174
TI  - Validation of the Sleep Regularity Index in Older Adults and Associations with
      Cardiometabolic Risk.
AB  - Sleep disturbances, including insufficient sleep duration and circadian
      misalignment, confer risk for cardiometabolic disease. Less is known about the
      association between the regularity of sleep/wake schedules and cardiometabolic
      risk. This study evaluated the external validity of a new metric, the Sleep
      Regularity Index (SRI), among older adults (n = 1978; mean age 68.7 +/- 9.2), as
      well as relationships between the SRI and cardiometabolic risk using data from
      the Multi-Ethnic Study of Atherosclerosis (MESA). Results indicated that sleep
      irregularity was associated with delayed sleep timing, increased daytime sleep
      and sleepiness, and reduced light exposure, but was independent of sleep
      duration. Greater sleep irregularity was also correlated with 10-year risk of
      cardiovascular disease and greater obesity, hypertension, fasting glucose,
      hemoglobin A1C, and diabetes status. Finally, greater sleep irregularity was
      associated with increased perceived stress and depression, psychiatric factors
      integrally tied to cardiometabolic disease. These results suggest that the SRI is
      a useful measure of sleep regularity in older adults. Additionally, sleep
      irregularity may represent a target for early identification and prevention of
      cardiometabolic disease. Future studies may clarify the causal direction of these
      effects, mechanisms underlying links between sleep irregularity and
      cardiometabolic risk, and the utility of sleep interventions in reducing
      cardiometabolic risk.

PMID- 30242175
TI  - Vps34-mediated macropinocytosis in Tuberous Sclerosis Complex 2-deficient cells
      supports tumorigenesis.
AB  - Tuberous Sclerosis Complex (TSC), a rare genetic disorder with mechanistic target
      of rapamycin complex 1 (mTORC1) hyperactivation, is characterized by multi-organ
      hamartomatous benign tumors including brain, skin, kidney, and lung
      (Lymphangioleiomyomatosis). mTORC1 hyperactivation drives metabolic reprogramming
      including glucose and glutamine utilization, protein, nucleic acid and lipid
      synthesis. To investigate the mechanisms of exogenous nutrients uptake in Tsc2
      deficient cells, we measured dextran uptake, a polysaccharide internalized via
      macropinocytosis. Tsc2-deficient cells showed a striking increase in dextran
      uptake (3-fold, p < 0.0001) relative to Tsc2-expressing cells, which was
      decreased (3-fold, p < 0.0001) with mTOR inhibitor, Torin1. Pharmacologic and
      genetic inhibition of the lipid kinase Vps34 markedly abrogated uptake of Dextran
      in Tsc2-deficient cells. Macropinocytosis was further increased in Tsc2-deficient
      cells that lack autophagic mechanisms, suggesting that autophagy inhibition leads
      to dependence on exogenous nutrient uptake in Tsc2-deficient cells. Treatment
      with a macropinocytosis inhibitor, ethylisopropylamiloride (EIPA), resulted in
      selective growth inhibition of Atg5-deficient, Tsc2-deficient cells (50%, p <
      0.0001). Genetic inhibition of autophagy (Atg5-/- MEFs) sensitized cells with
      Tsc2 downregulation to the Vps34 inhibitor, SAR405, resulting in growth
      inhibition (75%, p < 0.0001). Finally, genetic downregulation of Vps34 inhibited
      tumor growth and increased tumor latency in an in vivo xenograft model of TSC.
      Our findings show that macropinocytosis is upregulated with Tsc2-deficiency via a
      Vps34-dependent mechanism to support their anabolic state. The dependence of Tsc2
      deficient cells on exogenous nutrients may provide novel approaches for the
      treatment of TSC.

PMID- 30242176
TI  - New transgenic NIS reporter rats for longitudinal tracking of fibrogenesis by
      high-resolution imaging.
AB  - Fibrogenesis is the underlying mechanism of wound healing and repair. Animal
      models that enable longitudinal monitoring of fibrogenesis are needed to improve
      traditional tissue analysis post-mortem. Here, we generated transgenic reporter
      rats expressing the sodium iodide symporter (NIS) driven by the rat collagen type
      1 alpha-1 (Col1alpha1) promoter and demonstrated that fibrogenesis can be
      visualized over time using SPECT or PET imaging following activation of NIS
      expression by rotator cuff (RC) injury. Radiotracer uptake was first detected in
      and around the injury site day 3 following surgery, increasing through day 7-14,
      and declining by day 21, revealing for the first time, the kinetics of Col1alpha1
      promoter activity in situ. Differences in the intensity and duration of NIS
      expression/collagen promoter activation between individual RC injured Col1alpha1
      hNIS rats were evident. Dexamethasone treatment delayed time to peak NIS signals,
      showing that modulation of fibrogenesis by a steroid can be imaged with exquisite
      sensitivity and resolution in living animals. NIS reporter rats would facilitate
      studies in physiological wound repair and pathological processes such as fibrosis
      and the development of anti-fibrotic drugs.

PMID- 30242177
TI  - Physical ageing of spreading droplets in a viscous ambient phase.
AB  - In this work, we study the spontaneous spreading of water droplets immersed in
      oil and report an unexpectedly slow kinetic regime not described by previous
      spreading models. We can quantitatively describe the observed regime crossover
      and spreading rate in the late kinetic regime with an analytical model
      considering the presence of periodic metastable states induced by nanoscale
      topographic features (characteristic area ~4 nm2, height ~1 nm) observed via
      atomic force microscopy. The analytical model proposed in this work reveals that
      certain combinations of droplet volume and nanoscale topographic parameters can
      significantly hinder or promote wetting processes such as spreading, wicking, and
      imbibition.

PMID- 30242178
TI  - Superstatistical distribution of daily precipitation extremes: A worldwide
      assessment.
AB  - Maximum annual daily precipitation is a fundamental hydrologic variable that does
      not attain asymptotic conditions. Thus the classical extreme value theory (i.e.,
      the Fisher-Tippett's theorem) does not apply and the recurrent use of the
      Generalized Extreme Value distribution (GEV) to estimate precipitation quantiles
      for structural-design purposes could be inappropriate. In order to address this
      issue, we first determine the exact distribution of maximum annual daily
      precipitation starting from a Markov chain and in a closed analytical form under
      the hypothesis of stochastic independence. As a second step, we formulate a
      superstatistics conjecture of daily precipitation, meaning that we assume that
      the parameters of this exact distribution vary from a year to another according
      to probability distributions, which is supported by empirical evidence. We test
      this conjecture using the world GHCN database to perform a worldwide assessment
      of this superstatistical distribution of daily precipitation extremes. The
      performances of the superstatistical distribution and the GEV are tested against
      data using the Kolmogorov-Smirnov statistic. By considering the issue of model's
      extrapolation, that is, the evaluation of the estimated model against data not
      used in calibration, we show that the superstatistical distribution provides more
      robust estimations than the GEV, which tends to underestimate (7-13%) the
      quantile associated to the largest cumulative frequency. The superstatistical
      distribution, on the other hand, tends to overestimate (10-14%) this quantile,
      which is a safer option for hydraulic design. The parameters of the proposed
      superstatistical distribution are made available for all 20,561 worldwide sites
      considered in this work.

PMID- 30242180
TI  - HIF-1-dependent lipin1 induction prevents excessive lipid accumulation in choline
      deficient diet-induced fatty liver.
AB  - Adaptive responses to hypoxia regulate hepatic lipid metabolism, but their
      consequences in nonalcoholic fatty liver disease (NAFLD) are largely unknown.
      Here, we show that hypoxia inducible factor-1 (HIF-1), a key determinant of
      hypoxic adaptations, prevents excessive hepatic lipid accumulation in the
      progression of NAFLD. When exposed to a choline-deficient diet (CDD) for 4 weeks,
      the loss of hepatic Hif-1alpha gene accelerated liver steatosis with enhanced
      triglyceride accumulation in the liver compared to wild-type (WT) livers.
      Expression of genes involved in peroxisomal fatty acid oxidation was suppressed
      significantly in CDD-treated WT livers, whereas this reduction was further
      enhanced in Hif-1alpha-deficient livers. A lack of induction and nuclear
      accumulation of lipin1, a key regulator of the PPARalpha/PGC-1alpha pathway,
      could be attributed to impaired peroxisomal beta-oxidation in Hif-1alpha
      deficient livers. The lipin1-mediated binding of PPARalpha to the acyl CoA
      oxidase promoter was markedly reduced in Hif-1alpha-deficient mice exposed to a
      CDD. Moreover, forced Lipin1 expression restored the aberrant lipid accumulation
      caused by Hif-1alpha deletion in cells incubated in a choline-deficient medium.
      These results strongly suggest that HIF-1 plays a crucial role in the regulation
      of peroxisomal lipid metabolism by activating the expression and nuclear
      accumulation of lipin1 in NAFLD.

PMID- 30242179
TI  - Characterization of different fat depots in NAFLD using inflammation-associated
      proteome, lipidome and metabolome.
AB  - Non-alcoholic fatty liver disease (NAFLD) is recognized as a liver manifestation
      of metabolic syndrome, accompanied with excessive fat accumulation in the liver
      and other vital organs. Ectopic fat accumulation was previously associated with
      negative effects at the systemic and local level in the human body. Thus, we
      aimed to identify and assess the predictive capability of novel potential
      metabolic biomarkers for ectopic fat depots in non-diabetic men with NAFLD, using
      the inflammation-associated proteome, lipidome and metabolome. Myocardial and
      hepatic triglycerides were measured with magnetic spectroscopy while function of
      left ventricle, pericardial and epicardial fat, subcutaneous and visceral adipose
      tissue were measured with magnetic resonance imaging. Measured ectopic fat depots
      were profiled and predicted using a Random Forest algorithm, and by estimating
      the Area Under the Receiver Operating Characteristic curves. We have identified
      distinct metabolic signatures of fat depots in the liver (TAG50:1, glutamate,
      diSM18:0 and CE20:3), pericardium (N-palmitoyl-sphinganine, HGF, diSM18:0,
      glutamate, and TNFSF14), epicardium (sphingomyelin, CE20:3, PC38:3 and TNFSF14),
      and myocardium (CE20:3, LAPTGF-beta1, glutamate and glucose). Our analyses
      highlighted non-invasive biomarkers that accurately predict ectopic fat depots,
      and reflect their distinct metabolic signatures in subjects with NAFLD.

PMID- 30242181
TI  - Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis.
AB  - Aggregation of mutant superoxide dismutase 1 (SOD1) is a pathological hallmark of
      a subset of familial ALS patients. However, the possible role of misfolded wild
      type SOD1 in human ALS is highly debated. To ascertain whether or not misfolded
      SOD1 is a common pathological feature in non-SOD1 ALS, we performed a blinded
      histological and biochemical analysis of post mortem brain and spinal cord
      tissues from 19 sporadic ALS, compared with a SOD1 A4V patient as well as
      Alzheimer's disease (AD) and non-neurological controls. Multiple conformation- or
      misfolded-specific antibodies for human SOD1 were compared. These were generated
      independently by different research groups and were compared using standardized
      conditions. Five different misSOD1 staining patterns were found consistently in
      tissue sections from SALS cases and the SOD1 A4V patient, but were essentially
      absent in AD and non-neurological controls. We have established clear
      experimental protocols and provide specific guidelines for working, with
      conformational/misfolded SOD1-specific antibodies. Adherence to these guidelines
      will aid in the comparison of the results of future studies and better
      interpretation of staining patterns. This blinded, standardized and unbiased
      approach provides further support for a possible pathological role of misSOD1 in
      SALS.

PMID- 30242182
TI  - Signaling network between the dysregulated expression of microRNAs and mRNAs in
      propofol-induced developmental neurotoxicity in mice.
AB  - Mounting evidence has demonstrated that general anesthetics could induce acute
      neuroapoptosis in developing animals followed by long-term cognitive dysfunction,
      with the mechanisms remaining largely unknown. The aim of this study was to
      investigate the effect of the intravenous anesthetic propofol on the profiles of
      microRNAs (miRNAs) and messenger RNAs (mRNAs), and their interactive signaling
      networks in the developing mouse hippocampus. Postnatal day 7 (P7) mice were
      exposed to propofol for 3 hours. Hippocampi were harvested from both P7 (3 hours
      after exposure) and P60 mice for the analysis of the expression of 726 miRNAs and
      24,881 mRNAs, and apoptosis. Long-term memory ability of P60 mice was analyzed
      using the Morris Water Maze. Propofol induced acute apoptosis in the hippocampus,
      and impaired memory function of mice. There were 100 altered mRNAs and 18
      dysregulated miRNAs in the propofol-treated hippocampi compared with the
      intralipid-treated control tissues on P7. Bioinformatics analysis of these
      abnormally expressed genes on P7 indicated that 34 dysregulated miRNA-mRNA target
      pairs were related to pathological neurological and developmental disorder
      processes such as cell viability, cell morphology and migration, neural stem cell
      proliferation and neurogenesis, oligodendrocyte myelination, reactive oxygen
      species, and calcium signaling. Neonatal propofol exposure also resulted in the
      abnormal expression of 49 mRNAs and 4 miRNAs in P60 mouse hippocampi.
      Specifically, bioinformatics analysis indicates that among these dysregulated
      mRNAs and miRNAs, there were 2 dysregulated miRNA-mRNA targets pairs (Fam46a/miR
      363-3p and Rgs3/miR-363-3p) that might be related to the effect of propofol on
      long-term cognitive function. Collectively, our novel investigation indicates
      that acute and long-term dysregulated miRNA-mRNA signaling networks potentially
      participate in propofol-induced developmental neurotoxicity.

PMID- 30242183
TI  - Mechanical loading, an important factor in the evaluation of ion release from
      bone augmentation materials.
AB  - The controlled release of therapeutic inorganic ions from biomaterials is an
      emerging area of international research. One of the foci for this research is the
      development of materials, which spatially and temporally modulate therapeutic
      release, via controlled degradation in the intended physiological environment.
      Crucially however, our understanding of the release kinetics for such systems
      remains limited, particularly with respect to the influence of physiological
      loading. Consequently, this study was designed to investigate the effect of
      dynamic mechanical loading on a composite material intended to stabilize,
      reinforce and strengthen vertebral bodies. The composite material contains a
      borate glass engineered to release strontium as a therapeutic inorganic ion at
      clinically relevant levels over extended time periods. It was observed that both
      cyclic (6 MPa 2 Hz) and static (4.3 MPa) compressive loading significantly
      increased the release of strontium ions in comparison to the static unloaded
      case. The observed alterations in ion release kinetics suggest that the
      mechanical loading of the implantation environment should be considered when
      evaluating the ion release kinetics.

PMID- 30242184
TI  - Spin torque control of antiferromagnetic moments in NiO.
AB  - For a long time, there were no efficient ways of controlling antiferromagnets.
      Quite a strong magnetic field was required to manipulate the magnetic moments
      because of a high molecular field and a small magnetic susceptibility. It was
      also difficult to detect the orientation of the magnetic moments since the net
      magnetic moment is effectively zero. For these reasons, research on
      antiferromagnets has not been progressed as drastically as that on ferromagnets
      which are the main materials in modern spintronic devices. Here we show that the
      magnetic moments in NiO, a typical natural antiferromagnet, can indeed be
      controlled by the spin torque with a relatively small electric current density
      (~4 * 107 A/cm2) and their orientation is detected by the transverse resistance
      resulting from the spin Hall magnetoresistance. The demonstrated techniques of
      controlling and detecting antiferromagnets would outstandingly promote the
      methodologies in the recently emerged "antiferromagnetic spintronics".
      Furthermore, our results essentially lead to a spin torque antiferromagnetic
      memory.

PMID- 30242185
TI  - Pleistocene climate cycling and host plant association shaped the demographic
      history of the bark beetle Pityogenes chalcographus.
AB  - Historical climatic oscillations and co-evolutionary dependencies were key
      evolutionary drivers shaping the current population structure of numerous
      organisms. Here, we present a genome-wide study on the biogeography of the bark
      beetle Pityogenes chalcographus, a common and widespread insect in Eurasia. Using
      Restriction Associated DNA Sequencing, we studied the population structure of
      this beetle across a wide part of its western Palaearctic range with the goal of
      elucidating the role of Pleistocene glacial-interglacial cycling and its close
      relationship to its main host plant Norway spruce. Genetic distance among
      geographic sites was generally low, but clustering analysis revealed three
      genetically distinct groups, that is, southern, central/south-eastern, and north
      eastern locations. Thus, three key P. chalcographus glacial refugia were
      identified: in the Italian-Dinaric region, the Carpathians, and the Russian
      plain, shared with its main host. The current phylogeographic signal was affected
      by genetic divergence among geographically isolated refugia during glacial
      periods and postglacial re-establishment of genetic exchange through secondary
      contact, reflected by admixture among genetic groups. Additionally, certain life
      history traits, like the beetle's dispersal and reproductive behaviour,
      considerably influenced its demographic history. Our results will help to
      understand the biogeography of other scolytine beetles, especially species with
      similar life history traits.

PMID- 30242186
TI  - A Bioluminescent Cell Assay to Quantify Prion Protein Dimerization.
AB  - The prion protein (PrP) is a cell surface protein that in disease misfolds and
      becomes infectious causing Creutzfeldt-Jakob disease in humans, scrapie in sheep,
      and chronic wasting disease in deer and elk. Little is known regarding the
      dimerization of PrP and its role in disease. We developed a bioluminescent prion
      assay (BPA) to quantify PrP dimerization by bimolecular complementation of split
      Gaussia luciferase (GLuc) halves that are each fused to PrP. Fusion constructs
      between PrP and N- and C-terminal GLuc halves were expressed on the surface of
      RK13 cells (RK13-DC cells) and dimerized to yield a bioluminescent signal that
      was decreased in the presence of eight different antibodies to PrP. Dimerization
      of PrP was independent of divalent cations and was induced under stress.
      Challenge of RK13-DC cells with seven different prion strains did not lead to
      detectable infection but was measurable by bioluminescence. Finally, we used BPA
      to screen a compound library for compounds inhibiting PrP dimerization. One of
      the most potent compounds to inhibit PrP dimerization was JTC-801, which also
      inhibited prion replication in RML-infected ScN2a and SMB cells with an EC50 of
      370 nM and 220 nM, respectively. We show here that BPA is a versatile tool to
      study prion biology and to identify anti-prion compounds.

PMID- 30242187
TI  - Comparative Analysis of TM and Cytoplasmic beta-barrel Conformations Using Joint
      Descriptor.
AB  - Macroscopic descriptors have become valuable as coarse-grained features of
      complex proteins and are complementary to microscopic descriptors. Proteins
      macroscopic geometric features provide effective clues in the quantification of
      distant similarity and close dissimilarity searches for structural comparisons.
      In this study, we performed a systematic comparison of beta-barrels, one of the
      important classes of protein folds in various transmembrane (TM) proteins against
      cytoplasmic barrels to estimate the conformational features using a joint-based
      descriptor. The approach uses joint coordinates and dihedral angles (beta and
      gamma) based on the beta-strand joints and loops to determine the arrangements
      and propensities at the local and global levels. We then confirmed that there is
      a clear preference in the overall beta and gamma distribution, arrangements of
      beta-strands and loops, signature patterns, and the number of strand effects
      between TM and cytoplasmic beta-barrel geometries. As a robust and simple
      approach, we determine that the joint-based descriptor could provide a reliable
      static structural comparison aimed at macroscopic level between complex protein
      conformations.

PMID- 30242188
TI  - The pathogenesis linked to coenzyme Q10 insufficiency in iPSC-derived neurons
      from patients with multiple-system atrophy.
AB  - Multiple-system atrophy (MSA) is a neurodegenerative disease characterized by
      autonomic failure with various combinations of parkinsonism, cerebellar ataxia,
      and pyramidal dysfunction. We previously reported that functionally impaired
      variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway
      of coenzyme Q10, are associated with MSA. Here, we report functional deficiencies
      in mitochondrial respiration and the antioxidative system in induced pluripotent
      stem cell (iPSC)-derived neurons from an MSA patient with compound heterozygous
      COQ2 mutations. The functional deficiencies were rescued by site-specific
      CRISPR/Cas9-mediated gene corrections. We also report an increase in apoptosis of
      iPSC-derived neurons from MSA patients. Coenzyme Q10 reduced apoptosis of neurons
      from the MSA patient with compound heterozygous COQ2 mutations. Our results
      reveal that cellular dysfunctions attributable to decreased coenzyme Q10 levels
      are related to neuronal death in MSA, particularly in patients with COQ2
      variants, and may contribute to the development of therapy using coenzyme Q10
      supplementation.

PMID- 30242189
TI  - Magnetic Force-driven in Situ Selective Intracellular Delivery.
AB  - Intracellular delivery of functional materials holds great promise in biologic
      research and therapeutic applications but poses challenges to existing
      techniques, including the reliance on exogenous vectors and lack of selectivity.
      To address these problems, we propose a vector-free approach that utilizes
      millimeter-sized iron rods or spheres driven by magnetic forces to selectively
      deform targeted cells, which in turn generates transient disruption in cell
      membranes and enables the delivery of foreign materials into cytosols. A range of
      functional materials with the size from a few nanometers to hundreds of
      nanometers have been successfully delivered into various types of mammalian cells
      in situ with high efficiency and viability and minimal undesired effects.
      Mechanistically, material delivery is mediated by force-induced transient
      membrane disruption and restoration, which depend on actin cytoskeleton and
      calcium signaling. When used for siRNA delivery, CXCR4 is effectively silenced
      and cell migration and proliferation are significantly inhibited. Remarkably,
      cell patterns with various complexities are generated, demonstrating the unique
      ability of our approach in selectively delivering materials into targeted cells
      in situ. In summary, we have developed a magnetic force-driven intracellular
      delivery method with in situ selectivity, which may have tremendous applications
      in biology and medicine.

PMID- 30242190
TI  - Light sintering of ultra-smooth and robust silver nanowire networks embedded in
      poly(vinyl-butyral) for flexible OLED.
AB  - A conductive, uniform, and ultra-smooth flexible transparent composite film is
      produced by embedding silver nanowires (AgNWs) into poly(vinyl-butyral) (PVB)
      without pressure or high-temperature annealing. The adhesion of AgNWs was greatly
      improved by embedding them in PVB, and surface roughness and sheet resistance
      (Rs) improvements were achieved through the use of the intense pulsed light (IPL)
      method, which welds the interconnections among AgNWs in a short time without heat
      or pressure treatment. The sheet resistance of PVB/AgNWs with the IPL(PAI)
      composite film reaches 12.6 ohm/sq with a transmittance of 85.7% (at 550 nm); no
      clear changes in the sheet resistance are observed after a substrate bending and
      tape test, suggesting excellent flexibility. In the case of PAI, the change in
      sheet resistance was only 2.6% after a 2,000-bend test, and the resulting bending
      radius was less than 1 mm. When IPL was exposed to PVB/AgNWs, the figure of merit
      was 2.36 times higher than that without exposure. Finally, flexible OLEDs using
      PAI exhibited comparable or higher electroluminescent characteristics than other
      devices with well-known flexible electrodes-including indium-zinc-oxide on
      polymer plastic-which is a promising discovery for flexible optoelectronic
      applications.

PMID- 30242191
TI  - Tuning magnetocrystalline anisotropy by cobalt alloying in hexagonal Fe3Ge1.
AB  - We show using both experimental and theoretical methods that cobalt substitution
      in the hexagonal ferromagnet Fe3Ge suppresses the planar magnetic anisotropy and
      favors a uniaxial state. Uniaxial ferromagnetism is observed at room temperature
      for cobalt concentrations of only a few percent, and 10% substitution fully
      suppresses the planar magnetic structure at least down to 5 K, with only a small
      effect on the magnetization and Curie temperature. First principles calculations
      predict strong uniaxial magnetocrystalline anisotropy and promising permanent
      magnet properties for higher cobalt concentrations. Although these high Co
      concentrations were not realized experimentally, this work suggests that the rare
      earth-free Fe3Ge structure supports intrinsic magnetic properties that may enable
      promising permanent magnet performance.

PMID- 30242192
TI  - Homoarginine/ADMA ratio and homoarginine/SDMA ratio as independent predictors of
      cardiovascular mortality and cardiovascular events in lower extremity arterial
      disease.
AB  - Endothelial dysfunction plays a key role in development of atherosclerosis and
      lower extremity arterial disease (LEAD). Homoarginine, asymmetric
      dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are sensitive
      markers for endothelial dysfunction and independent risk factors for
      cardiovascular death. However, homoarginine may influence the proatherogenic
      effects of ADMA and SDMA suggesting homoarginine/ADMA ratio or homoarginine/SDMA
      ratio as further predictors for cardiovascular mortality. Therefore, we
      investigated the predictive value of homoarginine/ADMA ratio and
      homoarginine/SDMA ratio related to cardiovascular mortality and cardiovascular
      events in claudicant patients with LEAD. 151 patients with intermittent
      claudication were included in a prospective observational study (observation time
      7.7 +/- 2.5 years) with cardiovascular mortality as main outcome parameter and
      the occurrence of cardiovascular events as secondary outcome parameter.
      Homoarginine, ADMA and SDMA were measured by high-performance liquid
      chromatography at baseline. Low homoarginine/ADMA ratio and homoarginine/SDMA
      ratio were independently associated with higher cardiovascular mortality (HR
      2.803 [95% CI 1.178-6.674], p = 0.020; HR 2.782 [95% CI 1.061-7.290], p = 0.037,
      respectively) and higher incidence of cardiovascular events (HR 1.938 [95% CI
      1.015-3.700], p = 0.045; HR 2.397 [95% CI 1.243-4.623], p = 0.009, respectively).
      We observed that homoarginine/ADMA ratio and homoarginine/SDMA ratio are
      independent predictors for long-term cardiovascular mortality and events in
      claudicant patients with LEAD.

PMID- 30242193
TI  - Dose-dependent behavioural fever responses in desert locusts challenged with the
      entomopathogenic fungus Metarhizium acridum.
AB  - Behavioural fever is a common response to immune challenge in ectotherms and
      confers survival benefits. However, costs accrue rapidly as body temperature
      rises. Thus, the magnitude of adaptive fever responses might reflect the balance
      of costs and benefits. We investigated behavioural fever in desert locusts,
      Schistocerca gregaria, infected with the entomopathogenic fungus Metarhizium
      acridum. We first tracked the time course of behavioural fever in infected
      locusts, demonstrating that body temperatures rose on the day following
      inoculation (day 1), and reached peak intensity on the day after that (day 2).
      Subsequently, the magnitude of fever responses varied during a day, and locusts
      tended to exhibit high-intensity fever responses in the mornings when basking was
      first possible. We speculate that this may have resulted from increased fungal
      load caused by unimpeded growth overnight when locusts could not fever. We next
      inoculated locusts with different M. acridum doses ranging from 0 to ca. 75,000
      conidia. The magnitude of their behavioural fever responses on day 2 post
      inoculation was positively related to fungal dose. Thus, we demonstrate dose
      dependency in the behavioural fever responses of desert locusts and suggest that
      this may reflect the adaptive deployment of behavioural fever to minimize costs
      relative to benefits.

PMID- 30242194
TI  - Site-directed mutagenesis of Campylobacter concisus respiratory genes provides
      insight into the pathogen's growth requirements.
AB  - Campylobacter concisus is an emerging human pathogen found throughout the entire
      human oral-gastrointestinal tract. The ability of C. concisus to colonize diverse
      niches of the human body indicates the pathogen is metabolically versatile. C.
      concisus is able to grow under both anaerobic conditions and microaerophilic
      conditions. Hydrogen (H2) has been shown to enhance growth and may even be
      required. Analysis of several C. concisus genome sequences reveals the presence
      of two sets of genes encoding for distinct hydrogenases: a H2-uptake-type ("Hyd")
      complex and a H2-evolving hydrogenase ("Hyf"). Whole cells hydrogenase assays
      indicate that the former (H2-uptake) activity is predominant in C. concisus, with
      activity among the highest we have found for pathogenic bacteria. Attempts to
      generate site-directed chromosomal mutants were partially successful, as we could
      disrupt hyfB, but not hydB, suggesting that H2-uptake, but not H2-evolving
      activity, is an essential respiratory pathway in C. concisus. Furthermore, the
      tetrathionate reductase ttrA gene was inactivated in various C. concisus
      genomospecies. Addition of tetrathionate to the medium resulted in a ten-fold
      increase in cell yield for the WT, while it had no effect on the ttrA mutant
      growth. To our knowledge, this is the first report of mutants in C. concisus.

PMID- 30242195
TI  - Heterogeneity of material structure determines the stationary surface topography
      and friction.
AB  - The character of surface roughness and the force of friction in the stationary
      state after a sufficiently long run-in process are of key importance for numerous
      applications, e.g. for friction between road and tire. In the present paper, we
      study theoretically and experimentally the asymptotic worn state of a bi-phasic
      material that is arbitrarily heterogeneous in the contact plane, but homogeneous
      in the direction of the surface normal. Under the assumption of Archard's wear
      law in its local formulation, the asymptotic shape is found in the closed
      integral form. Given the surface profile, the coefficient of friction can be
      estimated, since the coefficient of friction is known to be strongly correlated
      with the mean square root value of the surface slope. The limiting surface
      profiles and the corresponding coefficient of friction are determined as
      functions of size, relative concentration and wear ratio of the phases. The
      results of numerical calculations are compared to and validated by experiments
      carried out on simplified model systems. The main conclusion is that the rms
      value of the surface slope is not influenced by the characteristic linear size of
      inclusions and depends solely on the relative concentration of phases, as well as
      the ratio of their wear coefficients.

PMID- 30242196
TI  - Agricultural landscapes and the Loire River influence the genetic structure of
      the marbled newt in Western France.
AB  - Amphibians are particularly sensitive to landscape fragmentation. Potential
      barriers between breeding sites can negatively influence the dispersal of
      individuals and increase genetic structure between populations. In this study, we
      genotyped 10 microsatellites for 334 marbled newts (Triturus marmoratus) at 11
      different locations in Western France. Samples were collected in different
      regions with contrasting agricultural landscapes (low and high proportion of
      arable land in the north and south, respectively). We found a strong genetic
      structure between the northern and southern sampling sites. Isolation by distance
      was recorded after 62 km, but within the northern region, little or no genetic
      structure was detected over large distances (up to 114 km). Genetic structure at
      shorter distance (43 km) was found between sites situated in landscapes with
      larger amounts of arable lands. A significant positive relationship was found
      between the pairwise genetic distance (Fst) between sites and the amount of
      arable land together with the distance between sites. Our results suggest that
      the Loire River might act as a corridor for the marbled newt, while arable land
      might act as a barrier. Finally, although a large city is located between
      sampling sites, no effect was detected on population structure.

PMID- 30242197
TI  - Genome-wide discovery of DNA polymorphisms by whole genome sequencing
      differentiates weedy and cultivated rice.
AB  - Analyzing the genome level DNA polymorphisms between weedy and cultivated rice is
      crucial to elucidate the molecular basis of weedy and agronomic traits, which in
      turn can enhance our ability to control weedy rice and its utilization for rice
      improvement. Here, we presented the genome-wide genetic variations between a
      weedy rice accession PSRR-1 and two cultivated rice accessions, Bengal and Nona
      Bokra, belonging to japonica and indica subspecies, respectively. The total
      number of SNPs and InDels in PSRR/Bengal was similar to that of Nona
      Bokra/Bengal, but was three times greater than that of PSRR/Nona Bokra. There
      were 11546 large-effect SNPs/InDels affecting 5673 genes, which most likely
      differentiated weedy rice from cultivated rice. These large effect DNA
      polymorphisms were mostly resulted in stop codon gain and least by start codon
      loss. Analysis of the molecular functions and biological processes of weedy rice
      specific SNPs/InDels indicated that most of these genes were involved in protein
      modification/phosphorylation, protein kinase activity, and protein/nucleotide
      binding. By integrating previous QTL mapping results with the DNA polymorphisms
      data, the candidate genes for seed dormancy and seed shattering were narrowed
      down. The genomic resource generated in this study will facilitate discovery of
      functional variants for weedy and agronomic traits.

PMID- 30242198
TI  - Heme-dependent Inactivation of 5-Aminolevulinate Synthase from Caulobacter
      crescentus.
AB  - The biosynthesis of heme is strictly regulated, probably because of the toxic
      effects of excess heme and its biosynthetic precursors. In many organisms, heme
      biosynthesis starts with the production of 5-aminolevulinic acid (ALA) from
      glycine and succinyl-coenzyme A, a process catalyzed by a homodimeric enzyme,
      pyridoxal 5'-phosphate (PLP)-dependent 5-aminolevulinate synthase (ALAS). ALAS
      activity is negatively regulated by heme in various ways, such as the repression
      of ALAS gene expression, degradation of ALAS mRNA, and inhibition of
      mitochondrial translocation of the mammalian precursor protein. There has been no
      clear evidence, however, that heme directly binds to ALAS to negatively regulate
      its activity. We found that recombinant ALAS from Caulobacter crescentus was
      inactivated via a heme-mediated feedback manner, in which the essential coenzyme
      PLP was rel eased to form the inactive heme-bound enzyme. The spectroscopic
      properties of the heme-bound ALAS showed that a histidine-thiolate hexa
      coordinated ferric heme bound to each subunit with a one-to-one stoichiometry.
      His340 and Cys398 were identified as the axial ligands of heme, and mutant ALASs
      lacking either of these ligands became resistant to heme-mediated inhibition.
      ALAS expressed in C. crescentus was also found to bind heme, suggesting that heme
      mediated feedback inhibition of ALAS is physiologically relevant in C.
      crescentus.

PMID- 30242199
TI  - Robust metric for quantifying the importance of stochastic effects on
      nanoparticle growth.
AB  - Comprehensive representation of nanoparticle dynamics is necessary for
      understanding nucleation and growth phenomena. This is critical in atmospheric
      physics, as airborne particles formed from vapors have significant but highly
      uncertain effects on climate. While the vapor-particle mass exchange driving
      particle growth can be described by a macroscopic, continuous substance for large
      enough particles, the growth dynamics of the smallest nanoparticles involve
      stochastic fluctuations in particle size due to discrete molecular collision and
      decay processes. To date, there have been no generalizable methods for
      quantifying the particle size regime where the discrete effects become negligible
      and condensation models can be applied. By discrete simulations of sub-10 nm
      particle populations, we demonstrate the importance of stochastic effects in the
      nanometer size range. We derive a novel, theory-based, simple and robust metric
      for identifying the exact sizes where these effects cannot be omitted for
      arbitrary molecular systems. The presented metric, based on examining the second-
      and first-order derivatives of the particle size distribution function, is
      directly applicable to experimental size distribution data. This tool enables
      quantifying the onset of condensational growth without prior information on the
      properties of the vapors and particles, thus allowing robust experimental
      resolving of nanoparticle formation physics.

PMID- 30242200
TI  - Faithful animal modelling of human glioma by using primary initiating cells and
      its implications for radiosensitization therapy [ARRIVE 1].
AB  - It has been reported that the ATM kinase inhibitor KU60019 preferentially
      radiosensitizes orthotopic high grade gliomas (HGG) driven by established U87 and
      U1242 cell lines bearing specific TP53 mutations. We wished to determine whether
      those results could be extended to tumors driven by primary glioma initiating
      cells (GIC) that closely mimic clinical tumors. Orthotopic HGG were developed in
      immunodeficient non-obese diabetic-severe combined immunodeficient (NOD-SCID)
      mice by intracranial injection of primary GIC isolated from the adult
      glioblastoma COMI (acronym of patient's name) and the pediatric anaplastic
      astrocytoma 239/12. Similar to the clinical tumors of origin, the orthotopic
      tumors COMI and 239/12 displayed different growth properties with a voluminous
      expansive lesion that exerted considerable mass effect on the adjacent structures
      and an infiltrating, gliomatosis-like growth pattern with limited compressive
      attitude, respectively. Significant elongations of median animal survival bearing
      the adult COMI tumor was observed after one KU60019 convection enhanced delivery
      followed by total 7.5 Gy of ionizing radiation delivered in fifteen 0.5 Gy
      fractions, as compared to animals treated with vehicle + ionizing radiation (105
      vs 89 days; ratio: 0.847; 95% CI of ratio 0.4969 to 1.198; P:0.0417) [ARRIVE 16].
      Similarly, a trend to increased median survival was observed with the
      radiosensitized pediatric tumor 239/12 (186 vs 167 days; ratio: 0.8978; 95% CI of
      ratio: 0.5352 to 1.260; P: 0.0891) [ARRIVE 16]. Our results indicate that
      radiosensitization by KU60019 is effective towards different orthotopic gliomas
      that faithfully mimic the clinical tumors and that multiple GIC-based animal
      models may be essential to develop novel therapeutic protocols for HGG
      transferable to the clinics.

PMID- 30242201
TI  - Lower serum calcium levels are a risk factor for a decrease in eGFR in a general
      non-chronic kidney disease population.
AB  - Association between serum calcium (Ca) levels and kidney dysfunction progression
      in a non-chronic kidney disease (CKD) population has not been well elucidated,
      especially in consideration for classical metabolic risk conditions such as
      hypertension, dyslipidemia, and diabetes, and those related to Ca metabolism.
      Among participants of the population-based Iwaki study of Japanese people, those
      with an estimated glomerular filtration rate (eGFR) ?60 ml/min/1.73 m2 and age
      ?40 years, and who attended the study consecutively in 2014 and 2015 were
      enrolled (gender (M/F): 218/380; age: 58.9 +/- 10.2). Regression analysis showed
      a significant correlation between serum Ca levels and a change in eGFR in the 1
      year period (?eGFR) after adjustment with multiple factors including those
      related to Ca metabolism (beta = 0.184, p < 0.001). When subjects were stratified
      into tertiles based on their serum Ca levels (higher >9.6 mg/dL, middle 9.4-9.6
      mg/dL, lower <9.4 mg/dL), lower serum Ca levels were a significant risk for a
      rapid decliner of eGFR designated as the lower one third of ?eGFR (<-4.40
      ml/min/1.73 m2) (odds ratio 2.41, 95% confidence interval 1.47-3.94). Lower serum
      Ca levels are a significant risk for rapid decrease in eGFR, independent of
      previously reported metabolic risk factors in this general population with non
      CKD, or eGFR ?60 ml/min/1.73 m2.

PMID- 30242202
TI  - Brain responses to different types of salience in antipsychotic naive first
      episode psychosis: An fMRI study.
AB  - Abnormal salience processing has been suggested to contribute to the formation of
      positive psychotic symptoms in schizophrenia and related conditions. Previous
      research utilising reward learning or anticipation paradigms has demonstrated
      cortical and subcortical abnormalities in people with psychosis, specifically in
      the prefrontal cortex, the dopaminergic midbrain and the striatum. In these
      paradigms, reward prediction errors attribute motivational salience to stimuli.
      However, little is known about possible abnormalities across different forms of
      salience processing in psychosis patients, and whether any such abnormalities
      involve the dopaminergic midbrain. The aim of our study was, therefore, to
      investigate possible alterations in psychosis in neural activity in response to
      various forms of salience: novelty, negative emotion, targetness (task-driven
      salience) and rareness/deviance. We studied 14 antipsychotic naive participants
      with first episode psychosis, and 37 healthy volunteers. During fMRI scanning,
      participants performed a visual oddball task containing these four forms of
      salience. Psychosis patients showed abnormally reduced signalling in the
      substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional
      salience and targetness; reduced striatal and occipital (lingual gyrus)
      signalling to novelty and negative emotional salience, reduced signalling in the
      amygdala, anterior cingulate cortex and parahippocamal gyrus to negative
      emotional salience, and reduced cerebellar signalling to novelty and negative
      emotional salience. Our results indicate alterations of several forms of salience
      processing in patients with psychosis in the midbrain SN/VTA, with additional
      subcortical and cortical regions also showing alterations in salience signalling,
      the exact pattern of alterations depending on the form of salience in question.

PMID- 30242203
TI  - Development of zebrafish paired and median fin musculature: basis for
      comparative, developmental, and macroevolutionary studies.
AB  - The model organism Dario rerio (zebrafish) is widely used in evo-devo and
      comparative studies. Nevertheless, little is known about the development and
      differentiation of the appendicular musculature in this fish. In this study, we
      examined the development of the muscles of all five zebrafish fin types
      (pectoral, pelvic, anal, dorsal and caudal). We describe the development of the
      muscles of these fins, including some muscles that were never mentioned in the
      literature, such as the interhypurales of the caudal fin. Interestingly, these
      caudal muscles are present in early stages but absent in adult zebrafishes. We
      also compare various stages of zebrafish fin muscle development with the
      configuration found in other extant fishes, including non-teleostean
      actinopterygians as well as cartilaginous fishes. The present work thus provides
      a basis for future developmental, comparative, evolutionary and evo-devo studies
      and emphasizes the importance of developmental works on muscles for a more
      comprehensive understanding of the origin, development and evolution of the
      appendicular appendages of vertebrate animals.

PMID- 30242204
TI  - Meningococcus serogroup C clonal complex ST-10217 outbreak in Zamfara State,
      Northern Nigeria.
AB  - After the successful roll out of MenAfriVac, Nigeria has experienced sequential
      meningitis outbreaks attributed to meningococcus serogroup C (NmC). Zamfara State
      in North-western Nigeria recently was at the epicentre of the largest NmC
      outbreak in the 21st Century with 7,140 suspected meningitis cases and 553 deaths
      reported between December 2016 and May 2017. The overall attack rate was 155 per
      100,000 population and children 5-14 years accounted for 47% (3,369/7,140) of
      suspected cases. The case fatality rate (CFR) among children 5-9 years was 10%,
      double that reported among adults >= 30 years (5%). NmC and pneumococcus
      accounted for 94% (172/184) and 5% (9/184) of the laboratory-confirmed cases,
      respectively. The sequenced NmC belonged to the ST-10217 clonal complex (CC). All
      serotyped pneumococci were PCV10 serotypes. The emergence of NmC ST-10217 CC
      outbreaks threatens the public health gains made by MenAfriVac, which calls for
      an urgent strategic action against meningitis outbreaks.

PMID- 30242205
TI  - Two-photon microscopy of Paneth cells in the small intestine of live mice.
AB  - Paneth cells are one of the principal epithelial cell types in the small
      intestine, located at the base of intestinal crypts. Paneth cells play key roles
      in intestinal host-microbe homeostasis via granule secretion, and their
      dysfunction is implicated in pathogenesis of several diseases including Crohn's
      disease. Despite their physiological importance, study of Paneth cells has been
      hampered by the limited accessibility and lack of labeling methods. In this
      study, we developed a simple in vivo imaging method of Paneth cells in the intact
      mouse small intestine by using moxifloxacin and two-photon microscopy (TPM).
      Moxifloxacin, an FDA-approved antibiotic, was used for labeling cells and its
      fluorescence was strongly observed in Paneth cell granules by TPM. Moxifloxacin
      labeling of Paneth cell granules was confirmed by molecular counterstaining.
      Comparison of Paneth cells in wild type, genetically obese (ob/ob), and germ-free
      (GF) mice showed different granule distribution. Furthermore, Paneth cell
      degranulation was observed in vivo. Our study suggests that TPM with moxifloxacin
      labeling can serve as a useful tool for studying Paneth cell biology and related
      diseases.

PMID- 30242206
TI  - In Vivo Electrocochleography in Hybrid Cochlear Implant Users Implicates TMPRSS3
      in Spiral Ganglion Function.
AB  - Cochlear implantation, a surgical method to bypass cochlear hair cells and
      directly stimulate the spiral ganglion, is the standard treatment for severe-to
      profound hearing loss. Changes in cochlear implant electrode array design and
      surgical approach now allow for preservation of acoustic hearing in the implanted
      ear. Electrocochleography (ECochG) was performed in eight hearing preservation
      subjects to assess hair cell and neural function and elucidate underlying genetic
      hearing loss. Three subjects had pathogenic variants in TMPRSS3 and five had
      pathogenic variants in genes known to affect the cochlear sensory partition. The
      mechanism by which variants in TMPRSS3 cause genetic hearing loss is unknown. We
      used a 500-Hz tone burst to record ECochG responses from an intracochlear
      electrode. Responses consist of a cochlear microphonic (hair cell) and an
      auditory nerve neurophonic. Cochlear microphonics did not differ between groups.
      Auditory nerve neurophonics were smaller, on average, in subjects with TMPRSS3
      deafness. Results of this proof-of-concept study provide evidence that pathogenic
      variants in TMPRSS3 may impact function of the spiral ganglion. While ECochG as a
      clinical and research tool has been around for decades, this study illustrates a
      new application of ECochG in the study of genetic hearing and deafness in vivo.

PMID- 30242209
TI  - Recent advances in the study of aggression.

PMID- 30242207
TI  - Comprehensive Evolutionary Analysis of the Major RNA-Induced Silencing Complex
      Members.
AB  - RNA-induced silencing complex (RISC) plays a critical role in small interfering
      RNA (siRNA) and microRNAs (miRNA) pathways. Accumulating evidence has
      demonstrated that the major RISC members (AGO, DICER, TRBP, PACT and GW182)
      represent expression discrepancies or multiple orthologues/paralogues in
      different species. To elucidate their evolutionary characteristics, an integrated
      evolutionary analysis was performed. Here, animal and plant AGOs were divided
      into three classes (multifunctional AGOs, siRNA-associated AGOs and piRNA
      associated AGOs for animal AGOs and multifunctional AGOs, siRNA-associated AGOs
      and complementary functioning AGOs for plant AGOs). Animal and plant DICERs were
      grouped into one class (multifunctional DICERs) and two classes (multifunctional
      DICERs and siRNA-associated DICERs), respectively. Protista/fungi AGOs or DICERs
      were specifically associated with the siRNA pathway. Additionally,
      TRBP/PACT/GW182 were identified only in animals, and all of them functioned in
      the miRNA pathway. Mammalian AGOs, animal DICERs and chordate TRBP/PACT were
      found to be monophyletic. A large number of gene duplications were identified in
      AGO and DICER groups. Taken together, we provide a comprehensive evolutionary
      analysis, describe a phylogenetic tree-based classification of the major RISC
      members and quantify their gene duplication events. These findings are
      potentially useful for classifying RISCs, optimizing species-specific RISCs and
      developing research model organisms.

PMID- 30242210
TI  - Necroinflammation emerges as a key regulator of hematopoiesis in health and
      disease.
AB  - The hematopoietic system represents an organ system with an exceptional capacity
      for the production of mature blood cells from a small and mostly quiescent pool
      of hematopoietic stem cells (HSCs). This extraordinary capacity includes self
      renewal but also the propensity to rapidly respond to extrinsic needs, such as
      acute infections, severe inflammation, and wound healing. In recent years, it
      became clear that inflammatory signals such as cytokines, chemokine and danger
      signals from pathogens (PAMPs) or dying cells (DAMPs) impact on HSCs, shaping
      their proliferation status, lineage bias, and repopulating ability and
      subsequently increasing the output of mature effector cells. However,
      inflammatory danger signals negatively impact on the capacity of HSCs to self
      renew and to maintain their stem cell capabilities. This is evidenced in
      conditions of chronic inflammation where bone marrow failure may originate from
      HSC exhaustion. Even in hematopoietic cancers, inflammatory signals shape the
      phenotype of the malignant clone as exemplified by necrosome-dependent
      inflammation elicited during malignant transformation in acute myeloid leukemia.
      Accordingly, understanding the contribution of inflammatory signals, and
      specifically necroinflammation, to HSC integrity, HSC long-term functionality,
      and malignant transformation has attracted substantial research and clinical
      interest. In this review, we highlight recent developments and open questions at
      the interplay between inflammation, regulated necrosis, and HSC biology in the
      context of blood cell development, acute and chronic inflammation, and
      hematopoietic cancer.

PMID- 30242208
TI  - Comparison of interleukin-2-inducible kinase (ITK) inhibitors and potential for
      combination therapies for T-cell lymphoma.
AB  - Patients with peripheral T-cell lymphomas generally have poor clinical outcomes
      with conventional chemotherapy. Recent advances have demonstrated that a large
      subgroup of PTCL are derived from follicular helper (Tfh) T-cells. These cases
      show a characteristic pattern of gene expression, which includes high-level
      protein expression of interleukin-2-inducible kinase (ITK). ITK is a member of
      the TEC family of kinases and normally has essential functions in regulating T
      cell receptor signalling and T-cell differentiation. Here we report a side-by
      side comparison of four ITK inhibitors. We investigate effects on apoptosis,
      phosphorylation of signaling molecules, calcium flux and migration. In line with
      a specific mechanism of action ONO7790500 and BMS509744 did not inhibit MEK1/2 or
      AKT phosphorylation although other ITK inhibitors, ibrutinib and PF-06465469, did
      have this effect. Specific ITKi had modest effects on apoptosis alone but there
      was definite synergy with doxorubicin, pictilisib (PI3Ki) and idelalisib
      (PI3Kdeltai). ITKi repressed migration of Jurkat cells caused by CXCL12 and the
      CXCR4 antagonist, plerixafor enhanced this effect. Overall ITKi may have several
      mechanisms of action that will be therapeutically useful in PTCL including
      reduction in survival and perturbation of trafficking.

PMID- 30242211
TI  - On the validity of metrics for defining penile distensibility phenotypes.

PMID- 30242214
TI  - U-tail as a guardian against invading RNAs.

PMID- 30242212
TI  - Gallium nitride nanowire as a linker of molybdenum sulfides and silicon for
      photoelectrocatalytic water splitting.
AB  - The combination of earth-abundant catalysts and semiconductors, for example,
      molybdenum sulfides and planar silicon, presents a promising avenue for the large
      scale conversion of solar energy to hydrogen. The inferior interface between
      molybdenum sulfides and planar silicon, however, severely suppresses charge
      carrier extraction, thus limiting the performance. Here, we demonstrate that
      defect-free gallium nitride nanowire is ideally used as a linker of planar
      silicon and molybdenum sulfides to produce a high-quality shell-core
      heterostructure. Theoretical calculations revealed that the unique electronic
      interaction and the excellent geometric-matching structure between gallium
      nitride and molybdenum sulfides enabled an ideal electron-migration channel for
      high charge carrier extraction efficiency, leading to outstanding performance. A
      benchmarking current density of 40 +/- 1 mA cm-2 at 0 V vs. reversible hydrogen
      electrode, the highest value ever reported for a planar silicon electrode without
      noble metals, and a large onset potential of +0.4 V were achieved under standard
      one-sun illumination.

PMID- 30242216
TI  - mRNA alterations mimic genetic mutations.

PMID- 30242215
TI  - Differential expression of the adult specifier E93 in the strepsipteran Xenos
      vesparum Rossi suggests a role in female neoteny.
AB  - Holometaboly is a key evolutionary innovation that has facilitated the
      spectacular radiation of insects. Despite the undeniable advantage of complete
      metamorphosis, the female of some holometabolous species have lost the typical
      holometabolous development through neoteny. In Xenos vesparum Rossi
      (Strepsiptera: Stylopidae), a derived species of the holometabolous endoparasitic
      order Strepsiptera, neotenic females reach sexual maturity without the pupal and
      the imaginal stages, thus retaining their larval morphology (with the exception
      of the anterior part of the body or cephalothorax), while males undergo normal
      pupal-based metamorphosis. Expression of the "adult-specifier" E93 factor has
      been shown to be required for proper metamorphosis in holometabolous insects.
      Here, we investigated the involvement of E93 in female neoteny by cloning XvE93.
      Interestingly, while we detected a clear up-regulation of XvE93 expression in
      pupal and adult stages of males, persistent low levels of XvE93 were detected in
      X. vesparum females. However, a specific up-regulation of XvE93 was observed in
      the cephalothorax of late 4th female instar larva, which correlates with the
      occurrence of neotenic-specific features in the anterior part of the female body.
      Moreover, the same expression dynamic in the cephalothorax and abdomen was also
      observed for other two critical metamorphic regulators, the anti-metamorphic XvKr
      h1 and the pupal specifier XvBr-C. The specific up-regulation of XvE93 and XvBr-C
      in the female cephalothorax seems to be the result of an increase in 20
      hydroxyecdysone (20E) signaling in this region for we detected higher expression
      levels of the 20E-dependent nuclear receptors XvHR3 and XvE75 in the
      cephalothorax. Overall, our results detect a sex-specific expression pattern of
      critical metamorphic genes in X. vesparum, suggesting that neoteny in
      Strepsiptera results from the modification of the normal expression of E93, Br-C
      and Kr-h1 genes.

PMID- 30242218
TI  - Assisted reproductive technologies increase risk of hypertension in offspring.

PMID- 30242217
TI  - Let's address burnout in oncologists and reimagine the way we work.

PMID- 30242219
TI  - Positive cardiac inotrope omecamtiv mecarbil activates muscle despite suppressing
      the myosin working stroke.
AB  - Omecamtiv mecarbil (OM) is a positive cardiac inotrope in phase-3 clinical trials
      for treatment of heart failure. Although initially described as a direct myosin
      activator, subsequent studies are at odds with this description and do not
      explain OM-mediated increases in cardiac performance. Here we show, via single
      molecule, biophysical experiments on cardiac myosin, that OM suppresses myosin's
      working stroke and prolongs actomyosin attachment 5-fold, which explains
      inhibitory actions of the drug observed in vitro. OM also causes the actin
      detachment rate to become independent of both applied load and ATP concentration.
      Surprisingly, increased myocardial force output in the presence of OM can be
      explained by cooperative thin-filament activation by OM-inhibited myosin
      molecules. Selective suppression of myosin is an unanticipated route to muscle
      activation that may guide future development of therapeutic drugs.

PMID- 30242220
TI  - Cerebello-thalamo-cortical hyperconnectivity as a state-independent functional
      neural signature for psychosis prediction and characterization.
AB  - Understanding the fundamental alterations in brain functioning that lead to
      psychotic disorders remains a major challenge in clinical neuroscience. In
      particular, it is unknown whether any state-independent biomarkers can
      potentially predict the onset of psychosis and distinguish patients from healthy
      controls, regardless of paradigm. Here, using multi-paradigm fMRI data from the
      North American Prodrome Longitudinal Study consortium, we show that individuals
      at clinical high risk for psychosis display an intrinsic "trait-like" abnormality
      in brain architecture characterized as increased connectivity in the cerebello
      thalamo-cortical circuitry, a pattern that is significantly more pronounced among
      converters compared with non-converters. This alteration is significantly
      correlated with disorganization symptoms and predictive of time to conversion to
      psychosis. Moreover, using an independent clinical sample, we demonstrate that
      this hyperconnectivity pattern is reliably detected and specifically present in
      patients with schizophrenia. These findings implicate cerebello-thalamo-cortical
      hyperconnectivity as a robust state-independent neural signature for psychosis
      prediction and characterization.

PMID- 30242221
TI  - Brain monoamine oxidase A in seasonal affective disorder and treatment with
      bright light therapy.
AB  - Increased cerebral monoamine oxidase A (MAO-A) levels have been shown in non
      seasonal depression using positron emission tomography (PET). Seasonal affective
      disorder (SAD) is a sub-form of major depressive disorder and is typically
      treated with bright light therapy (BLT). The serotonergic system is affected by
      season and light. Hence, this study aims to assess the relevance of brain MAO-A
      levels to the pathophysiology and treatment of SAD. Changes to cerebral MAO-A
      distribution (1) in SAD in comparison to healthy controls (HC), (2) after
      treatment with BLT and (3) between the seasons, were investigated in 24 patients
      with SAD and 27 HC using [11C]harmine PET. PET scans were performed in
      fall/winter before and after 3 weeks of placebo-controlled BLT, as well as in
      spring/summer. Cerebral MAO-A distribution volume (VT, an index of MAO-A density)
      did not differ between patients and HC at any of the three time-points. However,
      MAO-A VT decreased from fall/winter to spring/summer in the HC group (F1, 187.84
      = 4.79, p < 0.050), while SAD showed no change. In addition, BLT, but not
      placebo, resulted in a significant reduction in MAO-A VT (F1, 208.92 = 25.96, p <
      0.001). This is the first study to demonstrate an influence of BLT on human
      cerebral MAO-A levels in vivo. Furthermore, we show that SAD may lack seasonal
      dynamics in brain MAO-A levels. The lack of a cross-sectional difference between
      patients and HC, in contrast to studies in non-seasonal depression, may be due to
      the milder symptoms typically shown by patients with SAD.

PMID- 30242223
TI  - Design of ultrasensitive Ag-LaFeO3 methanol gas sensor based on quasi molecular
      imprinting technology.
AB  - An ultrasensitive methanol gas sensing device based on the quasi-molecular
      imprinting technology (quasi-MIT) is studied in this work. We applied the sol-gel
      method (ALS denotes Ag-LaFeO3 prepared by the sol-gel method) and combustion
      synthesis (ALC denotes Ag-LaFeO3 prepared by combustion synthesis) to prepare Ag
      LaFeO3 based sensors. The morphologies and structures of the Ag-LaFeO3 materials
      were examined via various detection techniques. The ALSM and ALCM sensor (ALSM
      and ALCM denotes the devices prepared by coating the ALS and ALC materials with
      methanol, respectively) fabricated using the sol-gel method and combustion
      synthesis combined with quasi-MIT exhibit good gas sensing properties to
      methanol, in contrast with the two devices (ALSW and ALCW denote the devices
      prepared for coating the ALS and ALC materials with water, respectively) without
      the use of quasi-MIT. The results show that quasi-MIT introduced the target gas
      in the fabrication process of the device, playing an important role in the design
      of the ultrasensitive methanol gas sensor. The sensing response and the optimum
      working temperature of ALSM and ALCM gas sensor are 52.29 and 155  degrees C and
      34.89 and 155  degrees C, respectively, for 5 ppm methanol, and the highest
      response to other gases is 8. The ALSM and ALCM gas sensors reveal good
      selectivity and response for methanol.

PMID- 30242222
TI  - Back-translating behavioral intervention for autism spectrum disorders to mice
      with blunted reward restores social abilities.
AB  - The mu opioid receptor (MOR) plays a critical role in modulating social behavior
      in humans and animals. Accordingly, MOR null mice display severe alterations in
      their social repertoire as well as multiple other behavioral deficits,
      recapitulating core and secondary symptoms of autism spectrum disorder (ASD).
      Such behavioral profile suggests that MOR dysfunction, and beyond this, altered
      reward processes may contribute to ASD etiopathology. Interestingly, the only
      treatments that proved efficacy in relieving core symptoms of ASD, early
      behavioral intervention programs, rely principally on positive reinforcement to
      ameliorate behavior. The neurobiological underpinnings of their beneficial
      effects, however, remain poorly understood. Here we back-translated applied
      behavior analysis (ABA)-based behavioral interventions to mice lacking the MOR
      (Oprm1-/-), as a model of autism with blunted reward processing. By associating a
      positive reinforcement, palatable food reward, to daily encounter with a wild
      type congener, we were able to rescue durably social interaction and preference
      in Oprm1-/- mice. Along with behavioral improvements, the expression of marker
      genes of neuronal activity and plasticity as well as genes of the
      oxytocin/vasopressin system were remarkably normalized in the reward/social
      circuitry. Our study provides further evidence for a critical involvement of
      reward processes in driving social behavior and opens new perspectives regarding
      therapeutic intervention in ASD.

PMID- 30242225
TI  - Assessing the efficacy of an ambulatory peripheral blood hematopoietic stem cell
      transplant program using reduced intensity conditioning in a low-middle-income
      country.
AB  - Efficacy of an ambulatory hematopoietic stem cell transplant (HSCT) program with
      a reduced intensity conditioning regimen (RIC) in malignant hematological
      diseases was assessed. We analyzed 217 patients who underwent HSCT from August
      2013 to July 2017. There were 78 (35.9%) HLA-identical, 56 (25.8%)
      haploidentical, and 83 (38.2%) autologous transplants. Two-year transplant
      related mortality (TRM) for HLA-identical, haploidentical, and auto grafts were
      20%, 25%, and 2.5%; relapse/progression was 44%, 60%, and 55%; overall survival
      (OS) was 61%, 44.8%, and 78.0%; and disease-free survival (DFS) was 36.8%, 26.5%,
      and 43.5%, respectively. Factors associated with a high risk of TRM were male sex
      (HR = 2.62, P = 0.031), fever and neutropenia (HR = 3.30, P = 0.023), and cell
      dose < 5 * 106 CD34 +/kg (HR = 4.24, P = 0.001); cGVHD was a protective factor
      for TRM (HR = 0.29, P = 0.022). Transfusion was associated with increased risk of
      relapse/progression in univariate and multivariate analysis (HR = 3.10, P = 0.001
      and HR = 3.30, P = 0.004); cGVHD was a protective factor (HR = 0.18, P = 0.001
      and HR = 0.17, P = 0.002). In a multivariate analysis for allo-HSCT, infections
      were associated with high risk of mortality (HR = 3.90, P = 0.016) and
      transfusion with reduced DFS (HR = 2.76, P = 0.029); for haplo-HSCT, CD34 + < 5 *
      106/kg was a risk factor for mortality and lower DFS (HR = 5.41, P = 0.001 and HR
      = 3.93, P = 0.001). Outcomes of our RIC-based outpatient transplant program are
      comparable to excellence centers in high-income countries.

PMID- 30242224
TI  - Influence of PEDOT:PSS crystallinity and composition on electrochemical
      transistor performance and long-term stability.
AB  - Owing to the mixed electron/hole and ion transport in the aqueous environment,
      poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)-based organic
      electrochemical transistor has been regarded as one of the most promising device
      platforms for bioelectronics. Nonetheless, there exist very few in-depth studies
      on how intrinsic channel material properties affect their performance and long
      term stability in aqueous environments. Herein, we investigated the correlation
      among film microstructural crystallinity/composition, device performance, and
      aqueous stability in poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)
      films. The highly organized anisotropic ordering in crystallized conducting
      polymer films led to remarkable device characteristics such as large
      transconductance (~20 mS), extraordinary volumetric capacitance (113 F.cm-3), and
      unprecedentedly high [MUC*] value (~490 F.cm-1V-1s-1). Simultaneously, minimized
      poly(styrenesulfonate) residues in the crystallized film substantially afforded
      marginal film swelling and robust operational stability even after >20-day water
      immersion, >2000-time repeated on-off switching, or high-temperature/pressure
      sterilization. We expect that the present study will contribute to the
      development of long-term stable implantable bioelectronics for neural
      recording/stimulation.

PMID- 30242226
TI  - Long-term health outcomes in survivors of childhood AML treated with allogeneic
      HSCT: a NOPHO-AML Study.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves event
      free survival in acute myeloid leukemia (AML); however, the burden of late
      effects may be increased. We compared health-related outcomes in childhood AML
      survivors treated according to the NOPHO-AML protocols either with or without
      allo-HSCT at age < 21 years. Out of the 147 eligible AML survivors treated with
      allo-HSCT, 95 (65%) and 53 (75%) of their eligible siblings completed a
      questionnaire. Their data were compared to corresponding data collected
      previously from NOPHO-AML survivors treated with chemotherapy only (CT) (n =
      101). The median follow-up was 12 (range 2-28) years after allo-HSCT and 47% had
      received total body irradiation (TBI)-based conditioning. Allo-HSCT survivors
      reported significantly more physical health limitations (39% vs 7%, p < 0.005),
      medications for cardiovascular disease (10% vs 1%, p < 0.05) and use of
      analgesics (32% vs 11%, p < 0.01) than CT survivors. Health problems prevented
      16% of the allo-HSCT survivors from attending school or managing a job vs. 3%
      among CT survivors (p < 0.05). Among 73 allo-HSCT survivors (age >= 15 years),
      seven females reported natural pregnancies and three males reported unassisted
      conceptions in partners. Survivors of childhood AML treated with allo-HSCT
      experienced more physical health limitations and used more medications than the
      survivors treated with chemotherapy only.

PMID- 30242227
TI  - Isoform-specific cleavage of neuroligin-3 reduces synapse strength.
AB  - The assembly and maintenance of synapses are dynamic processes that require
      bidirectional contacts between the pre- and postsynaptic structures. A network of
      adhesion molecules mediate this physical interaction between neurons. How
      synapses are disassembled and if there are distinct mechanisms that govern the
      removal of specific adhesion molecules remain unclear. Here, we report isoform
      specific proteolytic cleavage of neuroligin-3 in response to synaptic activity
      and protein kinase C signaling resulting in reduced synapse strength. Although
      neuroligin-1 and neuroligin-2 are not directly cleaved by this pathway, when
      heterodimerized with neuroligin-3, they too undergo proteolytic cleavage. Thus
      protein kinase C-dependent cleavage is mediated through neuroligin-3. Recent
      studies on glioma implicate the neuroligin-3 ectodomain as a mitogen. Here we
      demonstrate: (1) there are mechanisms governing specific adhesion molecule
      remodeling; (2) neuroligin-3 is a key regulator of neuroligin cleavage events;
      and (3) there are two cleavage pathways; basal and activity-dependent that
      produce the mitogenic form of neuroligin-3.

PMID- 30242228
TI  - Methylome-wide association findings for major depressive disorder overlap in
      blood and brain and replicate in independent brain samples.
AB  - We present the first large-scale methylome-wide association studies (MWAS) for
      major depressive disorder (MDD) to identify sites of potential importance for MDD
      etiology. Using a sequencing-based approach that provides near-complete coverage
      of all 28 million common CpGs in the human genome, we assay methylation in MDD
      cases and controls from both blood (N = 1132) and postmortem brain tissues (N =
      61 samples from Brodmann Area 10, BA10). The MWAS for blood identified several
      loci with P ranging from 1.91 * 10-8 to 4.39 * 10-8 and a resampling approach
      showed that the cumulative association was significant (P = 4.03 * 10-10) with
      the signal coming from the top 25,000 MWAS markers. Furthermore, a permutation
      based analysis showed significant overlap (P = 5.4 * 10-3) between the MWAS
      findings in blood and brain (BA10). This overlap was significantly enriched for a
      number of features including being in eQTLs in blood and the frontal cortex, CpG
      islands and shores, and exons. The overlapping sites were also enriched for
      active chromatin states in brain including genic enhancers and active
      transcription start sites. Furthermore, three loci located in GABBR2, RUFY3, and
      in an intergenic region on chromosome 2 replicated with the same direction of
      effect in the second brain tissue (BA25, N = 60) from the same individuals and in
      two independent brain collections (BA10, N = 81 and 64). GABBR2 inhibits neuronal
      activity through G protein-coupled second-messenger systems and RUFY3 is
      implicated in the establishment of neuronal polarity and axon elongation. In
      conclusion, we identified and replicated methylated loci associated with MDD that
      are involved in biological functions of likely importance to MDD etiology.

PMID- 30242229
TI  - Memory and cognition in schizophrenia.
AB  - Episodic memory deficits are consistently documented as a core aspect of
      cognitive dysfunction in schizophrenia patients, present from the onset of the
      illness and strongly associated with functional disability. Over the past decade,
      research using approaches from experimental cognitive neuroscience revealed
      disproportionate episodic memory impairments in schizophrenia (Sz) under high
      cognitive demand relational encoding conditions and relatively unimpaired
      performance under item-specific encoding conditions. These specific deficits in
      component processes of episodic memory reflect impaired activation and
      connectivity within specific elements of frontal-medial temporal lobe circuits,
      with a central role for the dorsolateral prefrontal cortex (DLPFC), relatively
      intact function of ventrolateral prefrontal cortex and variable results in the
      hippocampus. We propose that memory deficits can be understood within the broader
      context of cognitive deficits in Sz, where impaired DLPFC-related cognitive
      control has a broad impact across multiple cognitive domains. The therapeutic
      implications of these findings are discussed.

PMID- 30242230
TI  - Machine learning-guided intervention trials to predict treatment response at an
      individual patient level: an important second step following randomized clinical
      trials.

PMID- 30242231
TI  - Stress-inducible-stem cells: a new view on endocrine, metabolic and mental
      disease?

PMID- 30242233
TI  - Konjaku flour reduces obesity in mice by modulating the composition of the gut
      microbiota.
AB  - BACKGROUND: Changes in the intestinal flora composition is referred to as
      dysbiosis, which is related to obesity development, thus supporting the potential
      roles of nutrients acting on intestinal flora to exert salutary effects on
      energetic metabolism of host. Dietary fiber has been known to affect the
      composition of intestinal flora. The aim of the present study was to investigate
      the functional effects of konjac flour (KF) on obesity control in respect to
      improving inflammation, metabolism, and intestinal barrier function, and the
      possible association of the effects with intestinal flora composition changes.
      METHODS: Mice (n = 30) were randomly divided into control group (n = 10), high
      fat-diet (HFD) group (n = 10), and KF intervention group (n = 10), followed by
      feeding for 12 weeks and with adding a KF daily supplementation for the treatment
      group. Body weight, fat accumulation, inflammation, and energetic metabolism
      markers in multiple tissues and the gut microbiota of the mice were examined at
      the end of the experiment. RESULTS: The KF supplementation significantly reduced
      the gains in weight, fat mass, as well as adipocyte size of HFD mice and lowered
      the serum TC, leptin (LEP), thiobarbituric acid-reacting substance (TBARS), IL-6,
      and lipopolysaccharide (LPS) levels in HFD mice. KF also upregulated the
      expression of intestinal mucosa protein gene Intection and tight junction ZO-1 in
      HFD mice, as well as upregulate the expression of energy metabolism genes
      PPARalpha and CPT-1 as well as the fat metabolism gene HLS in livers and fat
      tissues, and downregulate that of fat synthesis gene PPARgamma (p < 0.05). The KF
      treatment increases the alpha-diversity and change the beta-diversity of the
      intestinal microflora in HFD mice and boosted the abundances of some obesity
      related beneficial microorganisms (such as Megasphaera elsdenii) in the
      intestinal microflora of HFD mice, while reduced those of harmful microorganisms
      (such as Alistipes, Alloprevotella, Bacteroides acidifaciens, and Parabacteroides
      goldsteinii). The abundance of Alistipes was positively correlated with weight,
      fat mass, serum TC, TG, LEP, IL-6, and LPS contents as well as PPARgamma gene
      expression; while notably and negatively related to the expression of CPT-1 and
      HLS genes (p < 0.01). KF remarkably increased the abundance of Aerococcaceae,
      while reduced that of Alistipes finegoldii (p < 0.01). CONCLUSIONS:
      Supplementation with KF achieves favorable effects on treating obesity, improving
      inflammatory response, metabolism, and intestinal barrier function, by regulating
      intestinal microfloral structure in HFD-fed mice.

PMID- 30242234
TI  - Plasma lipid profiling of tissue-specific insulin resistance in human obesity.
AB  - BACKGROUND/OBJECTIVES: Obesity-associated insulin resistance (IR) may develop in
      multiple organs, representing different aetiologies towards cardiometabolic
      diseases. This study aimed to identify distinct plasma lipid profiles in
      overweight/obese individuals who show muscle-IR and/or liver-IR.
      SUBJECTS/METHODS: Baseline data of the European multicenter DiOGenes project were
      used (n = 640; 401 women, nondiabetic BMI: 27-45 kg/m2). Muscle insulin
      sensitivity index (MISI) and hepatic insulin resistance index (HIRI) were derived
      from a 5-point oral glucose tolerance test. The 140 plasma lipids were quantified
      by liquid chromatography-mass spectrometry. Linear mixed models were used to
      evaluate associations between MISI, HIRI and plasma lipids. RESULTS: MISI was
      comparable between sexes while HIRI and triacylglycerol (TAG) levels were lower
      in women than in men. MISI was associated with higher lysophosphatidylcholine
      (LPC) levels (standardized (std)beta = 0.126; FDR-p = 0.032). Sex interactions
      were observed for associations between HIRI, TAG and diacylglycerol (DAG) lipid
      classes. In women, but not in men, HIRI was associated with higher levels of TAG
      (44 out of 55 species) and both DAG species (stdbeta: 0.139-0.313; FDR-p < 0.05),
      a lower odd-chain/even-chain TAG ratio (stdbeta = -0.182; FDR-p = 0.005) and a
      lower very-long-chain/long-chain TAG ratio (stdbeta = -0.156; FDR-p = 0.037).
      CONCLUSIONS: In overweight/obese individuals, muscle insulin sensitivity is
      associated with higher plasma LPC concentrations. Women have less hepatic IR and
      lower TAG than men. Nevertheless, hepatic IR is associated with higher plasma TAG
      and DAG concentrations and a lower abundance of odd-chain and very-long-chain TAG
      in women, but not in men. This suggests a more pronounced worsening of plasma
      lipid profile in women with the progression of hepatic IR.

PMID- 30242232
TI  - Parkin-dependent regulation of the MCU complex component MICU1.
AB  - The mitochondrial Ca2+ uniporter machinery is a multiprotein complex composed by
      the Ca2+ selective pore-forming subunit, the mitochondrial uniporter (MCU), and
      accessory proteins, including MICU1, MICU2 and EMRE. Their concerted action is
      required to fine-tune the uptake of Ca2+ into the mitochondrial matrix which both
      sustains cell bioenergetics and regulates the apoptotic response. To adequately
      fulfil such requirements and avoid impairment in mitochondrial Ca2+ handling, the
      intracellular turnover of all the MCU components must be tightly regulated. Here
      we show that the MCU complex regulator MICU1, but not MCU and MICU2, is rapidly
      and selectively degraded by the Ubiquitin Proteasome System (UPS). Moreover, we
      show that the multifunctional E3 ubiquitin ligase Parkin (PARK2), whose mutations
      cause autosomal recessive early-onset Parkinson's disease (PD), is a potential
      candidate involved in this process since its upregulation strongly decreases the
      basal level of MICU1. Parkin was found to interact with MICU1 and, interestingly,
      Parkin Ubl-domain, but not its E3-ubquitin ligase activity, is required for the
      degradation of MICU1, suggesting that in addition to the well documented role in
      the control of Parkin basal auto-inhibition, the Ubl-domain might exert important
      regulatory functions by acting as scaffold for the proteasome-mediated
      degradation of selected substrates under basal conditions, i.e. to guarantee
      their turnover. We have found that also MICU2 stability was affected upon Parkin
      overexpression, probably as a consequence of increased MICU1 degradation. Our
      findings support a model in which the PD-related E3 ubiquitin ligase Parkin
      directly participates in the selective regulation of the MCU complex regulator
      MICU1 and, indirectly, also of the MICU2 gatekeeper, thus indicating that Parkin
      loss of function could contribute to the impairment of the ability of
      mitochondria to handle Ca2+ and consequently to the pathogenesis of PD.

PMID- 30242235
TI  - Prenatal education of overweight or obese pregnant women to prevent childhood
      overweight (the ETOIG study): an open-label, randomized controlled trial.
AB  - BACKGROUND: We aimed to evaluate whether pre and perinatal education of pregnant
      women would reduce childhood overweight. METHODS: Four French centers included
      women at <=21 gestational weeks (GWs) with body mass index (BMI) >25 kg/m2 before
      pregnancy. Patients were randomized to a control group (routine care including at
      least one dietary visit) or an intervention group (2 individuals (26 and 30 GW)
      and 4 group sessions (21, 28, 35 GW, 2 months postpartum)) aimed at educating the
      future mother regarding infant and maternal nutrition. The primary objective was
      to reduce post-natal excessive weight gain in the infant from birth to 2 years
      (NCT00804765). This project was funded by a grant from the National Programme for
      Hospital Research (PHRC-2007 French Ministry of Health). RESULTS: We included 275
      women (BMI: 32.5 kg/m2). The rate of post-natal excessive weight gain was similar
      in the intervention (n = 132) and control (n = 136) groups by intention to treat
      (ITT: 59.1% vs 60.3% respectively, p = 0.84) in available data (AD, n = 206) and
      by per-protocol analysis (PP, n = 177). Two years after delivery, normalization
      of maternal BMI and number of infants with BMI < 19 kg/m2 were not significantly
      different in the interventional group in ITT and in the control group. Although
      not significantly different in ITT, normalization of maternal BMI was more
      frequent in AD (n = 149: 12.9% vs 3.8%, p = 0.04) and 2-year-old infant BMIs were
      less likely to be >19 kg/m2 in the intervention group in AD (n = 204: 0% vs 6.8%,
      p = 0.014) and PP (n = 176: 0% vs 6.4%, p = 0.03). CONCLUSIONS: An education and
      nutritional counseling program for overweight women, starting after 3 months of
      gestation, did not significantly change post-natal excessive weight gain of
      infants or prevent overweight in mothers and children 2 years after delivery.

PMID- 30242236
TI  - Editors' note: big data in obesity research.

PMID- 30242237
TI  - Protein synthesis signaling in skeletal muscle is refractory to whey protein
      ingestion during a severe energy deficit evoked by prolonged exercise and caloric
      restriction.
AB  - BACKGROUND: Exercise and protein ingestion preserve muscle mass during moderate
      energy deficits. OBJECTIVE: To determine the molecular mechanisms by which
      exercise and protein ingestion may spare muscle mass during severe energy deficit
      (5500 kcal/day). DESIGN: Fifteen overweight, but otherwise healthy men, underwent
      a pre-test (PRE), caloric restriction (3.2 kcals/kg body weight/day) + exercise
      (45 min one-arm cranking + 8 h walking) for 4 days (CRE), followed by a control
      diet (CD) for 3 days, with a caloric content similar to pre-intervention while
      exercise was reduced to less than 10,000 steps per day. During CRE, participants
      ingested either whey protein (PRO, n = 8) or sucrose (SU, n = 7) (0.8 g/kg body
      weight/day). Muscle biopsies were obtained from the trained and untrained
      deltoid, and vastus lateralis. RESULTS: Following CRE and CD, serum
      concentrations of leptin, insulin, and testosterone were reduced, whereas
      cortisol and the catabolic index (cortisol/total testosterone) increased. The
      Akt/mTor/p70S6K pathway and total eIF2alpha were unchanged, while total 4E-BP1
      and Thr37/464E-BP1 were higher. After CRE, plasma BCAA and EAA were elevated,
      with a greater response in PRO group, and total GSK3beta, pSer9GSK3beta,
      pSer51eIF2alpha, and pSer51eIF2alpha/total eIF2alpha were reduced, with a greater
      response of pSer9GSK3beta in the PRO group. The changes in signaling were
      associated with the changes in leptin, insulin, amino acids, cortisol,
      cortisol/total testosterone, and lean mass. CONCLUSIONS: During severe energy
      deficit, pSer9GSK3beta levels are reduced and human skeletal muscle becomes
      refractory to the anabolic effects of whey protein ingestion, regardless of
      contractile activity. These effects are associated with the changes in lean mass
      and serum insulin, testosterone, and cortisol concentrations.

PMID- 30242238
TI  - Can big data solve a big problem? Reporting the obesity data landscape in line
      with the Foresight obesity system map.
AB  - BACKGROUND: Obesity research at a population level is multifaceted and complex.
      This has been characterised in the UK by the Foresight obesity systems map,
      identifying over 100 variables, across seven domain areas which are thought to
      influence energy balance, and subsequent obesity. Availability of data to
      consider the whole obesity system is traditionally lacking. However, in an era of
      big data, new possibilities are emerging. Understanding what data are available
      can be the first challenge, followed by an inconsistency in data reporting to
      enable adequate use in the obesity context. In this study we map data sources
      against the Foresight obesity system map domains and nodes and develop a
      framework to report big data for obesity research. Opportunities and challenges
      associated with this new data approach to whole systems obesity research are
      discussed. METHODS: Expert opinion from the ESRC Strategic Network for Obesity
      was harnessed in order to develop a data source reporting framework for obesity
      research. The framework was then tested on a range of data sources. In order to
      assess availability of data sources relevant to obesity research, a data mapping
      exercise against the Foresight obesity systems map domains and nodes was carried
      out. RESULTS: A reporting framework was developed to recommend the reporting of
      key information in line with these headings: Background; Elements; Exemplars;
      Content; Ownership; Aggregation; Sharing; Temporality (BEE-COAST). The new BEE
      COAST framework was successfully applied to eight exemplar data sources from the
      UK. 80% coverage of the Foresight obesity systems map is possible using a wide
      range of big data sources. The remaining 20% were primarily biological
      measurements often captured by more traditional laboratory based research.
      CONCLUSIONS: Big data offer great potential across many domains of obesity
      research and need to be leveraged in conjunction with traditional data for
      societal benefit and health promotion.

PMID- 30242239
TI  - The effects of provider-prescribed obesogenic drugs on post-laparoscopic sleeve
      gastrectomy outcomes: a retrospective cohort study.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is one of the most commonly
      performed bariatric procedures and has proven effective in providing weight loss.
      However, considerable variance has been noted in the degree of weight loss.
      Physician prescription practices may be negatively affecting weight loss post-LSG
      and, thus, contributing to the broad range of weight loss outcomes. The aim of
      our study was to determine whether commonly prescribed obesogenic medications
      negatively affect weight loss outcomes post-LSG. SUBJECTS/METHODS: This single
      center retrospective cohort study performed at a University hospital included 323
      patients (>=18 years) within the University California, San Diego Healthcare
      System who underwent LSG between 2007 and 2016. We identified a list of 32
      commonly prescribed medications that have weight gain as a side effect. We
      compared the percent excess weight loss (%EWL) of patients divided into two
      groups based on post-LSG exposure to obesogenic medications. A linear regression
      model was used to analyze %EWL at 12 months post-LSG while controlling for age,
      initial body mass index (BMI), and use of leptogenic medications. RESULTS: A
      total of 150 patients (Meds group) were prescribed obesogenic medications within
      the one-year post-LSG follow up period, whereas 173 patients (Control group) were
      not prescribed obesogenic medications. The Meds group lost significantly less
      weight compared to the Control group (%EWL +/- SEM at 12 months 53.8 +/- 2.4 n =
      78, 65.0 +/- 2.6, n = 84 respectively, P = 0.002). This difference could not be
      attributed to differences in age, gender, initial BMI, co-morbidities, or
      prescription of leptogenic medications between the two groups. CONCLUSIONS: The
      use of provider-prescribed obesogenic medications was associated with worse
      weight loss outcomes post-LSG. Closer scrutiny of patient medications may be
      necessary to help improve outcomes of weight loss treatments.

PMID- 30242240
TI  - Phenotypic and genetic analysis of an adult cohort with extreme obesity.
AB  - CONTEXT: Adult extreme obesity (EO) is a growing health concern. The prevalence
      of known obesity associated co-morbidities namely cardio-metabolic and neuro
      psychiatric disease in EO is not fully established. The contribution of
      pathogenic genetic variants, previously implicated in early childhood onset
      obesity, to adult EO is also not established. OBJECTIVE: We undertook phenotypic
      and genetic analysis of adult patients with extreme obesity (EO, BMI > 50).
      Specifically, we assessed the prevalence of eating disorders, cardio-metabolic,
      and neuro-psychiatric disease and the presence of pathogenic variants in known
      monogenic obesity genes. DESIGN: A total of 55 patients with EO from a single
      site bariatric surgery referral program were assessed for the presence of eating
      disorders, cardio-metabolic, and neuro-psychiatric disease. The 54 obese (O)
      patients with a BMI < 50 from the same program were identified for phenotypic
      comparison. The 45 EO patients underwent whole exome sequencing to identify
      deleterious variants in known monogenic obesity genes. OUTCOMES: (1) Presence of
      eating disorders, cardio-metabolic, and neuro-psychiatric disease in EO compared
      to O. (2) Onset of obesity in the EO group. (3) Presence of deleterious variants
      in genes previously implicated in monogenic obesity in the EO group. RESULTS: The
      EO group had higher prevalence of lifetime neuro-psychiatric disease (67.3% vs.
      37%, p = 0.001) and sleep apnea (74.6% vs. 51.9%, p = 0.01) but lower prevalence
      of type 2 diabetes (30.1% vs. 50%, p = 0.045) compared to O. There were no
      significant differences in binge eating, dyslipidemia, hypertension, and cardiac
      disease. In the EO group, we found previously unreported singleton variants in
      NTRK2 (pS667W, bio-informatically predicted to be deleterious) and BDNF (pE23K).
      No previously confirmed loss of function variants in monogenic obesity genes were
      found. CONCLUSIONS: Adults with EO have significantly increased prevalence of
      neuro-psychiatric disease and a possibly lower burden of type 2 diabetes compared
      to less obese patients. Known monogenic causes of obesity were not highly
      prevalent in this cohort. Further studies are warranted to confirm these
      preliminary findings.

PMID- 30242241
TI  - Genome-wide analysis of polymorphism * sodium interaction effect on blood
      pressure identifies a novel 3'-BCL11B gene desert locus.
AB  - Excessive sodium intake is a global risk factor for hypertension. Sodium effects
      on blood pressure vary from person to person; hence, high-risk group targeting
      based on personal genetic information can play a complementary role to ongoing
      population preventive approaches to reduce sodium consumption. To identify
      genetic factors that modulate sodium effects on blood pressure, we conducted a
      population-based genome-wide interaction analysis in 8,768 Japanese subjects,
      which was >3 times larger than a similar previous study. We tested 7,135,436
      polymorphisms in the discovery cohort, and loci that met suggestive significance
      were further examined in an independent replication cohort. We found that an
      interaction between a novel 3'-BCL11B gene desert locus and daily sodium
      consumption was significantly associated with systolic blood pressure in both
      discovery and replication cohorts under the recessive model. Further statistical
      analysis of rs8022678, the sentinel variant of the 3'-BCL11B gene desert locus,
      showed that differences in mean systolic blood pressure between high and low
      sodium consumption subgroups were 5.9 mm Hg (P = 8.8 * 10-12) in rs8022678 A
      carriers and -0.3 mm Hg (P = 0.27) in rs8022678 A non-carriers, suggesting that
      the rs8022678 genotype can classify persons into sodium-sensitive (A carriers)
      and sodium-insensitive (A non-carriers) subgroups. Our results implied that
      rs8022678 A carriers may receive a greater benefit from sodium-lowering
      interventions than non-carriers.

PMID- 30242243
TI  - Correction: Gene expression profiling identifies FYN as an important molecule in
      tamoxifen resistance and a predictor of early recurrence in patients treated with
      endocrine therapy.
AB  - Since the online publication of the above article, the authors have noted errors
      in subfigures 1c and 3b. Therefore, new images of the original
      immmunocytochemistry stainings have been obtained for Fig. 1c, and the Western
      blots for siRNA-mediated FYN knockdown in Fig. 3b were repeated. The amended
      versions of Figs. 1c and 3b are now provided.

PMID- 30242242
TI  - Spatiotemporal segregation of human marginal zone and memory B cell populations
      in lymphoid tissue.
AB  - Human memory B cells and marginal zone (MZ) B cells share common features such as
      the expression of CD27 and somatic mutations in their IGHV and BCL6 genes, but
      the relationship between them is controversial. Here, we show phenotypic
      progression within lymphoid tissues as MZ B cells emerge from the mature naive B
      cell pool via a precursor CD27-CD45RBMEM55+ population distant from memory cells.
      By imaging mass cytometry, we find that MZ B cells and memory B cells occupy
      different microanatomical niches in organised gut lymphoid tissues. Both
      populations disseminate widely between distant lymphoid tissues and blood, and
      both diversify their IGHV repertoire in gut germinal centres (GC), but
      nevertheless remain largely clonally separate. MZ B cells are therefore not
      developmentally contiguous with or analogous to classical memory B cells despite
      their shared ability to transit through GC, where somatic mutations are acquired.

PMID- 30242244
TI  - LMTK3 is essential for oncogenic KIT expression in KIT-mutant GIST and melanoma.
AB  - Certain cancers, including gastrointestinal stromal tumor (GIST) and subsets of
      melanoma, are caused by somatic KIT mutations that result in KIT receptor
      tyrosine kinase constitutive activity, which drives proliferation. The treatment
      of KIT-mutant GIST has been revolutionized with the advent of KIT-directed cancer
      therapies. KIT tyrosine kinase inhibitors (TKI) are superior to conventional
      chemotherapy in their ability to control advanced KIT-mutant disease. However,
      these therapies have a limited duration of activity due to drug-resistant
      secondary KIT mutations that arise (or that are selected for) during KIT TKI
      treatment. To overcome the problem of KIT TKI resistance, we sought to identify
      novel therapeutic targets in KIT-mutant GIST and melanoma cells using a human
      tyrosine kinome siRNA screen. From this screen, we identified lemur tyrosine
      kinase 3 (LMTK3) and herein describe its role as a novel KIT regulator in KIT
      mutant GIST and melanoma cells. We find that LMTK3 regulated the translation rate
      of KIT, such that loss of LMTK3 reduced total KIT, and thus KIT downstream
      signaling in cancer cells. Silencing of LMTK3 decreased cell viability and
      increased cell death in KIT-dependent, but not KIT-independent GIST and melanoma
      cell lines. Notably, LMTK3 silencing reduced viability of all KIT-mutant cell
      lines tested, even those with drug-resistant KIT secondary mutations.
      Furthermore, targeting of LMTK3 with siRNA delayed KIT-dependent GIST growth in a
      xenograft model. Our data suggest the potential of LMTK3 as a target for
      treatment of patients with KIT-mutant cancer, particularly after failure of KIT
      TKIs.

PMID- 30242245
TI  - High efficiency of the aldosterone-to-renin ratio in precisely detecting primary
      aldosteronism.
AB  - The aldosterone-to-renin ratio (ARR) is extensively used for primary
      aldosteronism detection. Chemiluminescence immune assay (CLIA) is newly applied
      in aldosterone and renin detection for calculating the aldosterone-to-renin
      ratio. The performance of new ARR in aldosteronism detection is poorly evaluated.
      We aim to estimate the diagnostic value of this new aldosterone-to-renin ratio by
      highly standardized and clinically based protocol. Four hundred and forty-two
      patients were enrolled in our retrospective study. They went to the first
      affiliated hospital of Sun Yat-sen University with difficult-to-control
      hypertension. Primary aldosteronism diagnosis was based on clinical criteria,
      including a saline infusion test and other necessary inspections. ARR was
      calculated from plasma aldosterone and renin measured by CLIA. The cutoff value
      was determined and the diagnostic value was evaluated. The cutoff value of ARR
      for primary aldosteronism diagnosis was 28.3, with a sensitivity of 87.6%,
      specificity of 100%, negative-predictive value of 96.4%, and positive-predictive
      value of 100%. Then, we found that Age was weakly correlated with ARR. The cutoff
      values of ARR for primary aldosteronism diagnosis in 26-45-, 46-65-, and 66-85
      year-old patients were, respectively, 29.45, 27.95, and 28.4, with sensitivities
      of 87.5%, 87.7%, and 87.5%, specificities of 100% for all, negative-predictive
      values of 97.7%, 94.3%, and 96.3%, and positive-predictive values of 100% for
      all. ARR generated by CLIA is a good diagnostic test for primary aldosteronism
      without making a false-positive diagnosis. Although ARR is correlated with age,
      ARR cutoff values for different ages are not more efficient than that for total
      sample in primary aldosteronism diagnosis.

PMID- 30242246
TI  - Pre-hypertension and subclinical carotid damage: a meta-analysis.
AB  - The association between pre-hypertension (pre-HTN) and subclinical carotid damage
      is poorly defined. We performed a meta-analysis of ultrasonographic studies
      assessing carotid intima-media thickness (IMT) in untreated pre-HTN subjects. The
      OVID-MEDLINE, PubMed, and Cochrane CENTRAL databases were searched for English
      language articles without time restriction up to February 2018 through focused,
      high sensitive search strategies. Studies were identified by crossing the
      following search terms: "pre-hypertension", "high normal blood pressure",
      "carotid intima-media thickness", "carotid atherosclerosis", "ultrasonography".
      Overall, 7645 subjects (3374 normotensive, 1936 untreated pre-HTN, and 2335 HTN
      individuals) of both genders were included in seven studies. In the pooled study
      population, common carotid IMT showed a progressive increase from normotensive
      (723 +/- 39 um) to pre-HTN (779 +/- 45 um) (standardized mean difference, SMD
      0.36 +/- 0.08, CI 0.34-0.46, p < 0.0001) and to HTN subjects (858 +/- 82 um) (SMD
      0.39 +/- 0.07, CI 0.26-0.54, p = 0.002 vs. pre-HT). The statistical difference
      did not change after correction for publication bias and was not affected by a
      single study effect. Our meta-analysis shows that carotid IMT in pre-HTN subjects
      is intermediate between normotensive and HTN individuals. These findings support
      the view that pre-HTN is an unfavourable condition that should be properly
      managed in order to prevent vascular damage.

PMID- 30242247
TI  - Nanoparticles in neutrophil clothing.

PMID- 30242248
TI  - Wavefront manipulation based on transmissive acoustic metasurface with membrane
      type hybrid structure.
AB  - We designed and demonstrated a gradient acoustic metasurface to manipulate the
      transmissive wavefront. The gradient metasurface is composed of eight elements
      based on membrane-type hybrid structures, whose thickness and width are about 1/5
      and 1/20 of the incident wavelength, respectively. Here, we employ acoustic
      theory to analyze the transmission spectrum and phase gradient of the
      metasurface, the properties of high transmission efficiency and discrete phase
      shifts over the full [Formula: see text] range can be achieved simultaneously. By
      appropriate selection of the phase profile along the transverse coordinate of the
      metasurface or the angle of incident wave, the transmissive wavefront
      manipulations based on metasurface can be obtained as expected from the
      generalized Snell's law, such as anomalous refraction, acoustic cloak based on
      flat focusing, acoustic self-bending beam, conversion of propagating wave to
      surface wave and negative refraction. Our gradient metasurface may have potential
      application in low-loss acoustic devices.

PMID- 30242249
TI  - Saccadic inhibition interrupts ongoing oculomotor activity to enable the rapid
      deployment of alternate movement plans.
AB  - Diverse psychophysical and neurophysiological results show that oculomotor
      networks are continuously active, such that plans for making the next eye
      movement are always ongoing. So, when new visual information arrives
      unexpectedly, how are those plans affected? At what point can the new information
      start guiding an eye movement, and how? Here, based on modeling and simulation
      results, we make two observations that are relevant to these questions. First, we
      note that many experiments, including those investigating the phenomenon known as
      "saccadic inhibition", are consistent with the idea that sudden-onset stimuli
      briefly interrupt the gradual rise in neural activity associated with the
      preparation of an impending saccade. And second, we show that this stimulus
      driven interruption is functionally adaptive, but only if perception is fast. In
      that case, putting on hold an ongoing saccade plan toward location A allows the
      oculomotor system to initiate a concurrent, alternative plan toward location B
      (where a stimulus just appeared), deliberate (briefly) on the priority of each
      target, and determine which plan should continue. Based on physiological data, we
      estimate that the advantage of this strategy, relative to one in which any plan
      once initiated must be completed, is of several tens of milliseconds per saccade.

PMID- 30242250
TI  - Respiratory Syncytial Virus induces the classical ROS-dependent NETosis through
      PAD-4 and necroptosis pathways activation.
AB  - Respiratory syncytial virus (RSV) is a major cause of diseases of the respiratory
      tract in young children and babies, being mainly associated with bronchiolitis.
      RSV infection occurs primarily in pulmonary epithelial cells and, once infection
      is established, an immune response is triggered and neutrophils are recruited. In
      this study, we investigated the mechanisms underlying NET production induced by
      RSV. We show that RSV induced the classical ROS-dependent NETosis in human
      neutrophils and that RSV was trapped in DNA lattices coated with NE and MPO.
      NETosis induction by RSV was dependent on signaling by PI3K/AKT, ERK and p38 MAPK
      and required histone citrullination by PAD-4. In addition, RIPK1, RIPK3 and MLKL
      were essential to RSV-induced NETosis. MLKL was also necessary to neutrophil
      necrosis triggered by the virus, likely promoting membrane-disrupting pores,
      leading to neutrophil lysis and NET extrusion. Finally, we found that RSV
      infection of alveolar epithelial cells or lung fibroblasts triggers NET-DNA
      release by neutrophils, indicating that neutrophils can identify RSV-infected
      cells and respond to them by releasing NETs. The identification of the mechanisms
      responsible to mediate RSV-induced NETosis may prove valuable to the design of
      new therapeutic approaches to treat the inflammatory consequences of RSV
      bronchiolitis in young children.

PMID- 30242251
TI  - Acoustic properties of vowel production in Mandarin-speaking patients with post
      stroke dysarthria.
AB  - This study investigated the acoustic features of vowel production in Mandarin
      speaking patients with post-stroke dysarthria (PSD). The subjects included 31
      native Mandarin-speaking patients with PSD (age: 25-83 years old) and 38
      neurologically normal adults in a similar age range (age: 21-76 years old). Each
      subject was recorded producing a list of Mandarin monosyllables that included six
      monophthong vowels (i.e., /a, i, u, ?, y, o/) embedded in the /CV/ context. The
      patients' speech samples were evaluated by two native Mandarin speakers. The
      evaluation scores were then used to classify all patients into two levels of
      severity: mild or moderate-to-severe. Formants (F1 and F2) were extracted from
      each vowel token. Results showed that all vowel categories in the patients with
      PSD were produced with more variability than in the healthy speakers. Great
      overlaps between vowel categories and reduced vowel space were observed in the
      patients. The magnitude of the vowel dispersion and overlap between vowel
      categories increased as a function of the severity of the disorder. The
      deviations of the vowel acoustic features in the patients in comparison to the
      healthy speakers may provide guidance for clinical rehabilitation to improve the
      speech intelligibility of patients with PSD.

PMID- 30242252
TI  - The intragenic mRNA-microRNA regulatory network during telogen-anagen hair
      follicle transition in the cashmere goat.
AB  - It is widely accepted that the periodic cycle of hair follicles is controlled by
      the biological clock, but the molecular regulatory mechanisms of the hair
      follicle cycle have not been thoroughly studied. The secondary hair follicle of
      the cashmere goat is characterized by seasonal periodic changes throughout life.
      In the hair follicle cycle, the initiation of hair follicles is of great
      significance for hair follicle regeneration. To provide a reference for hair
      follicle research, our study compared differences in mRNA expression and microRNA
      expression during the growth and repose stages of cashmere goat skin samples.
      Through microRNA and mRNA association analysis, we found microRNAs and target
      genes that play major regulatory roles in hair follicle initiation. We further
      constructed an mRNA-microRNA interaction network and found that hair follicle
      initiation and development were related to MiR-195 and the genes CHP1, SMAD2,
      FZD6 and SIAH1.

PMID- 30242254
TI  - E. coli Nissle 1917 is a safe mucosal delivery vector for a birch-grass pollen
      chimera to prevent allergic poly-sensitization.
AB  - Allergic poly-sensitization affects a large number of allergic patients and poses
      a great challenge for their treatment. In this study we evaluated the effects of
      the probiotic Escherichia coli Nissle 1917 (EcN) expressing a birch and grass
      pollen allergen chimera 'Bet v 1, Phl p 1 and Phl p 5' (EcN-Chim) on allergy
      prevention after oral or intranasal application in poly-sensitized mice. In
      contrast to oral application, intranasal pretreatment with EcN-Chim prior to poly
      sensitization led to a significant reduction of lung inflammation (eosinophils,
      IL-5, and IL-13 in bronchoalveolar lavage) along with suppressed levels of
      allergen-specific serum IgE. The suppression was associated with increased levels
      of allergen-specific IgA in lungs and serum IgG2a along with increased Foxp3, TGF
      beta, and IL-10 mRNA in bronchial lymph nodes. In vitro EcN induced high levels
      of IL-10 and IL-6 in both lung and intestinal epithelial cells. Importantly,
      using in vivo imaging techniques we demonstrated that intranasally applied EcN do
      not permanently colonize nose, lung, and gut and this strain might therefore be a
      safe delivery vector against allergy in humans. In conclusion, our data show that
      intranasal application of recombinant EcN expressing a multiallergen chimera
      presents a novel and promising treatment strategy for prevention of allergic poly
      sensitization.

PMID- 30242253
TI  - Bcl-xl as the most promising Bcl-2 family member in targeted treatment of
      chondrosarcoma.
AB  - Chondrosarcomas are malignant cartilage tumors showing relative resistance to
      conventional chemo- and radiotherapy. Previous studies showed that chondrosarcoma
      cells could be sensitized to chemotherapy by inhibiting the Bcl-2 family members
      Bcl-2, Bcl-xl and Bcl-w using ABT-737. In this study we explored the specific
      role of Bcl-2 family members to identify the most important player in
      chondrosarcoma cell survival and chemo resistance. Immunohistochemistry was
      performed on tissue microarrays containing 137 conventional chondrosarcomas of
      different grades. Selective inhibition of Bcl-2 (S55746) or Bcl-xl (WEHI-539 or A
      1155463) and the combination with doxorubicin or cisplatin was investigated in a
      panel of 8 chondrosarcoma cell lines using presto blue viability assays and
      caspase 3/7 glo apoptosis assays. In addition Bcl-2 and Bcl-xl inhibition was
      investigated in an orthotopic Swarm Rat Chondrosarcoma (SRC) model. Bcl-2 and Bcl
      xl were most abundantly expressed in the primary tumors, and expression increased
      with increasing histological grade. A subset of chondrosarcoma cell lines was
      sensitive to selective inhibition of Bcl-xl, and synergy was observed with
      doxorubicin or cisplatin in 3 out of 8 chondrosarcoma cell lines resulting in
      apoptosis. Conversely, selective inhibition of Bcl-2 was not effective in
      chondrosarcoma cell lines and could not sensitize to chemotherapy. In vivo,
      selective inhibition of Bcl-xl, but not Bcl-2 resulted in a decrease in tumor
      growth rate, even though no sensitization to doxorubicin was observed. These
      results suggest that among the Bcl-2 family members, Bcl-xl is most important for
      chondrosarcoma survival. Further research is needed to validate whether single or
      combination treatment with chemotherapy will be beneficial for chondrosarcoma
      patients.

PMID- 30242255
TI  - Sun-induced fluorescence and gross primary productivity during a heat wave.
AB  - Remote sensing of sun-induced chlorophyll fluorescence (SIF) has been suggested
      as a promising approach for probing changes in global terrestrial gross primary
      productivity (GPP). To date, however, most studies were conducted in situations
      when/where changes in both SIF and GPP were driven by large changes in the
      absorbed photosynthetically active radiation (APAR) and phenology. Here we
      quantified SIF and GPP during a short-term intense heat wave at a Mediterranean
      pine forest, during which changes in APAR were negligible. GPP decreased linearly
      during the course of the heat wave, while SIF declined slightly initially and
      then dropped dramatically during the peak of the heat wave, temporally coinciding
      with a biochemical impairment of photosynthesis inferred from the increase in the
      uptake ratio of carbonyl sulfide to carbon dioxide. SIF thus accounted for less
      than 35% of the variability in GPP and, even though it responded to the
      impairment of photosynthesis, appears to offer limited potential for
      quantitatively monitoring GPP during heat waves in the absence of large changes
      in APAR.

PMID- 30242256
TI  - Biomechanical interplay between anisotropic re-organization of cells and the
      surrounding matrix underlies transition to invasive cancer spread.
AB  - The root cause of cancer mortality and morbidity is the metastatic spread of the
      primary tumor, but underlying mechanisms remain elusive. Here we investigate
      biomechanical interactions that may accompany invasive spread of melanoma cells.
      We find that metastatic cells can exert considerable traction forces and modify
      local collagen organization within a 3D matrix. When this re-organization is
      mimicked using a nano-fabricated model of aligned extracellular matrix fibers,
      metastatic cells, including less invasive melanoma cells, were in turn induced to
      align, elongate and migrate, guided by the local ridge orientations. Strikingly,
      we found that this aligned migration of melanoma cells was accompanied by long
      range regulation of cytoskeletal remodeling that show anisotropic stiffening in
      the direction of fiber orientation suggestive of a positive feedback between ECM
      fiber alignment and forces exerted by cancer cells. Taken together, our findings
      suggest that the invasive spread of cancer cells can be defined by complex
      interplay with the surrounding matrix, during which they both modify the matrix
      and use the matrix alignment as a persistent migration cue, leading to more
      extensive and rapid invasive spread.

PMID- 30242259
TI  - Scaffold-mediated delivery for non-viral mRNA vaccines.
AB  - mRNA is increasingly being recognized as a promising alternative to pDNA in gene
      vaccinations. Only recently, owing to the needs of cancer immunotherapies, has
      the biomaterials/gene delivery community begun to develop new biomaterial
      strategies for immunomodulation. Here, we report a novel way to use implantable
      porous scaffolds as a local gene delivery depot to enhance mRNA vaccine
      immunization in vitro, and in vivo when compared with conventional bolus
      injections. We first evaluated transfection efficiencies of single-stranded mRNA
      condensed and charge neutralized with two lipids (Lipofectamine Messenger MAXTM
      LM-MM and StemfectTM SF) and two cationic polymers (in vivo-jetPEITM, Poly (beta
      amino ester)) as gene carriers. As SF demonstrated highest in vitro transfection
      and cell viability, it was selected for subsequent porous polymer scaffold
      loading trials. Enhanced in vitro transfection of SF:mRNA nanoparticle-loaded
      poly (2-hydroxyethyl methacrylate) (pHEMA) scaffolds was also observed with a
      DC2.4 cell line. Improved sustained local release and local transgene expression
      were also demonstrated with SF:mRNA nanoparticle-loaded pHEMA scaffolds in vivo
      compared with bolus injections. Our results suggest that mRNA polyplex-loaded
      scaffolds may be a superior alternative to either repeated bolus immunizations or
      ex vivo transfection cell immunotherapies.

PMID- 30242257
TI  - The Cytotoxic Necrotizing Factor of Yersinia pseudotuberculosis (CNFy) is Carried
      on Extracellular Membrane Vesicles to Host Cells.
AB  - In this study we show Yersinia pseudotuberculosis secretes membrane vesicles
      (MVs) that contain different proteins and virulence factors depending on the
      strain. Although MVs from Y. pseudotuberculosis YPIII and ATCC 29833 had many
      proteins in common (68.8% of all the proteins identified), those located in the
      outer membrane fraction differed significantly. For instance, the MVs from Y.
      pseudotuberculosis YPIII harbored numerous Yersinia outer proteins (Yops) while
      they were absent in the ATCC 29833 MVs. Another virulence factor found solely in
      the YPIII MVs was the cytotoxic necrotizing factor (CNFy), a toxin that leads to
      multinucleation of host cells. The ability of YPIII MVs to transport this toxin
      and its activity to host cells was verified using HeLa cells, which responded in
      a dose-dependent manner; nearly 70% of the culture was multinucleated after
      addition of 5 ug/ml of the purified YPIII MVs. In contrast, less than 10% were
      multinucleated when the ATCC 29833 MVs were added. Semi-quantification of CNFy
      within the YPIII MVs found this toxin is present at concentrations of 5 ~ 10 ng
      per ug of total MV protein, a concentration that accounts for the cellular
      responses seen.

PMID- 30242258
TI  - Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia.
AB  - The Wnt signalling pathway, one of the core de-regulated pathways in chronic
      lymphocytic leukaemia (CLL), is activated in only a subset of patients through
      somatic mutations. Here we describe alternative, microenvironment-dependent
      mechanisms of Wnt activation in malignant B cells. We show that tumour cells
      specifically induce Notch2 activity in mesenchymal stromal cells (MSCs) required
      for the transcription of the complement factor C1q. MSC-derived C1q in turn
      inhibits Gsk3-beta mediated degradation of beta-catenin in CLL cells.
      Additionally, stromal Notch2 activity regulates N-cadherin expression in CLL
      cells, which interacts with and further stabilises beta-catenin. Together, these
      stroma Notch2-dependent mechanisms induce strong activation of canonical Wnt
      signalling in CLL cells. Pharmacological inhibition of the Wnt pathway impairs
      microenvironment-mediated survival of tumour cells. Similarly, inhibition of
      Notch signalling diminishes survival of stroma-protected CLL cells in vitro and
      disease engraftment in vivo. Notch2 activation in the microenvironment is a pre
      requisite for the activation of canonical Wnt signalling in tumour cells.

PMID- 30242260
TI  - In-vivo shift of the microbiota in oral biofilm in response to frequent sucrose
      consumption.
AB  - Caries is associated with shifts of microbiota in dental biofilms and primarily
      driven by frequent sucrose consumption. Data on environmentally induced in vivo
      microbiota shifts are scarce therefore we investigated the influence of frequent
      sucrose consumption on the oral biofilm. Splint systems containing enamel slabs
      were worn for 3 * 7 days with 7-day intervals to obtain oral biofilm samples.
      After a three-month dietary change of sucking 10 g of sucrose per day in addition
      to the regular diet, biofilm was obtained again at the end of the second phase.
      The microbiota was analysed using Illumina MiSeq amplicon sequencing (v1-v2
      region). In addition, roughness of the enamel surface was measured with laser
      scanning microscopy. The sucrose phase resulted in significant differences in
      beta-diversity and significantly decreased species richness. It was marked by a
      significant increase in abundance of streptococci, specifically Streptococcus
      gordonii, Streptococcus parasanguinis and Streptococcus sanguinis. Enamel surface
      roughness began to increase, reflecting initial impairment of dental enamel
      surface. The results showed that frequent sucrose consumption provoked
      compositional changes in the microbiota, leading to an increase of non-mutans
      streptococci, hence supporting the extended ecological plaque hypothesis and
      emphasizing the synergy of multiple bacterial species in the development of
      caries.

PMID- 30242261
TI  - Tick galactosyltransferases are involved in alpha-Gal synthesis and play a role
      during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector
      development.
AB  - The carbohydrate Galalpha1-3Galbeta1-(3)4GlcNAc-R (alpha-Gal) is produced in all
      mammals except for humans, apes and old world monkeys that lost the ability to
      synthetize this carbohydrate. Therefore, humans can produce high antibody titers
      against alpha-Gal. Anti-alpha-Gal IgE antibodies have been associated with tick
      induced allergy (i.e. alpha-Gal syndrome) and anti-alpha-Gal IgG/IgM antibodies
      may be involved in protection against malaria, leishmaniasis and Chagas disease.
      The alpha-Gal on tick salivary proteins plays an important role in the etiology
      of the alpha-Gal syndrome. However, whether ticks are able to produce endogenous
      alpha-Gal remains currently unknown. In this study, the Ixodes scapularis genome
      was searched for galactosyltransferases and three genes were identified as
      potentially involved in the synthesis of alpha-Gal. Heterologous gene expression
      in alpha-Gal-negative cells and gene knockdown in ticks confirmed that these
      genes were involved in alpha-Gal synthesis and are essential for tick feeding.
      Furthermore, these genes were shown to play an important role in tick-pathogen
      interactions. Results suggested that tick cells increased alpha-Gal levels in
      response to Anaplasma phagocytophilum infection to control bacterial infection.
      These results provided the molecular basis of endogenous alpha-Gal production in
      ticks and suggested that tick galactosyltransferases are involved in vector
      development, tick-pathogen interactions and possibly the etiology of alpha-Gal
      syndrome in humans.

PMID- 30242262
TI  - Ancient and modern anticonvulsants act synergistically in a KCNQ potassium
      channel binding pocket.
AB  - Epilepsy has been treated for centuries with herbal remedies, including leaves of
      the African shrub Mallotus oppositifolius, yet the underlying molecular
      mechanisms have remained unclear. Voltage-gated potassium channel isoforms KCNQ2
      5, predominantly KCNQ2/3 heteromers, underlie the neuronal M-current, which
      suppresses neuronal excitability, protecting against seizures. Here, in silico
      docking, mutagenesis and cellular electrophysiology reveal that two components of
      M. oppositifolius leaf extract, mallotoxin (MTX) and isovaleric acid (IVA), act
      synergistically to open neuronal KCNQs, including KCNQ2/3 channels.
      Correspondingly, MTX and IVA combine to suppress pentylene tetrazole-induced
      tonic seizures in mice, whereas individually they are ineffective. Co
      administering MTX and IVA with the modern, synthetic anticonvulsant retigabine
      creates a further synergy that voltage independently locks KCNQ2/3 open.
      Leveraging this synergy, which harnesses ancient and modern medicines to exploit
      differential KCNQ isoform preferences, presents an approach to developing safe
      yet effective anticonvulsants.

PMID- 30242263
TI  - Reconfiguring surface functions using visible-light-controlled metal-ligand
      coordination.
AB  - Most surfaces are either static or switchable only between "on" and "off" states
      for a specific application. It is a challenge to develop reconfigurable surfaces
      that can adapt to rapidly changing environments or applications. Here, we
      demonstrate fabrication of surfaces that can be reconfigured for user-defined
      functions using visible-light-controlled Ru-thioether coordination chemistry. We
      modify substrates with Ru complex Ru-H2O. To endow a Ru-H2O-modified substrate
      with a certain function, a functional thioether ligand is immobilized on the
      substrate via Ru-thioether coordination. To change the surface function, the
      immobilized thioether ligand is cleaved from the substrate by visible-light
      induced ligand dissociation, and then another thioether ligand with a distinct
      function is immobilized on the substrate. Different thioethers endow the surface
      with different functions. Based on this strategy, we rewrite surface patterns,
      manipulate protein adsorption, and control surface wettability. This strategy
      enables the fabrication of reconfigurable surfaces with customizable functions on
      demand.

PMID- 30242265
TI  - The emerging role of ADAM metalloproteinases in immunity.
AB  - Proteolysis is an irreversible physiological process that can result in the
      termination or activation of protein function. Many transmembrane proteins that
      are involved in the cellular communication between immune cells and structural
      cells - for example, Notch, CD23, CD44, and membrane-anchored cytokines and their
      receptors - are cleaved by the ADAM (a disintegrin and metalloproteinase) family
      of enzymes. Here, we review recent insights into the molecular activation,
      substrate specificity and function of ADAM proteins in the development and
      regulation of the immune system, with a particular focus on the roles of ADAM10
      and ADAM17.

PMID- 30242264
TI  - Examining the Role of Cone-expressed RPE65 in Mouse Cone Function.
AB  - Efficient chromophore supply is paramount for the continuous function of
      vertebrate cone photoreceptors. It is well established that isomerization of all
      trans- to 11-cis- retinoid in the retinal pigmented epithelium by RPE65 is a key
      reaction in this process. Mutations in RPE65 result in a disrupted chromophore
      supply, retinal degeneration, and blindness. Interestingly, RPE65 has recently
      been found to also be expressed in cone photoreceptors in several species,
      including mouse and human. However, the functional role of cone-expressed RPE65
      has remained unknown. Here, we used loss and gain of function approaches to
      investigate this issue. First, we compared the function of cones from control and
      RPE65-deficient mice. Although we found that deletion of RPE65 partially
      suppressed cone dark adaptation, the interpretation of this result was
      complicated by the abnormal cone structure and function caused by the chromophore
      deficiency in the absence of RPE65 in the pigmented epithelium. As an alternative
      approach, we generated transgenic mice to express human RPE65 in the cones of
      mice where RPE65 expression is normally restricted to the pigmented epithelium.
      Comparison of control (RPE65-deficient) and transgenic (RPE65-expressing) cones
      revealed no morphological or functional changes, with only a slight delay in dark
      adaptation, possibly caused by the buffering of retinoids by RPE65. Together, our
      results do not provide any evidence for a functional role of RPE65 in mouse
      cones. Future studies will have to determine whether cone-expressed RPE65 plays a
      role in maintaining the long-term homeostasis of retinoids in cones and their
      function and survival, particularly in humans.

PMID- 30242266
TI  - The impact of air exchange rate on ambient air pollution exposure and
      inequalities across all residential parcels in Massachusetts.
AB  - Individual housing characteristics can modify outdoor ambient air pollution
      infiltration through air exchange rate (AER). Time and labor-intensive methods
      needed to measure AER has hindered characterization of AER distributions across
      large geographic areas. Using publicly-available data and regression models
      associating AER with housing characteristics, we estimated AER for all
      Massachusetts residential parcels. We conducted an exposure disparities analysis,
      considering ambient PM2.5 concentrations and residential AERs. Median AERs (h-1)
      with closed windows for winter and summer were 0.74 (IQR: 0.47-1.09) and 0.36
      (IQR: 0.23-0.57), respectively, with lower AERs for single family homes. Across
      residential parcels, variability of indoor PM2.5 concentrations of ambient origin
      was twice that of ambient PM2.5 concentrations. Housing parcels above the 90th
      percentile of both AER and ambient PM2.5 (i.e., the leakiest homes in areas of
      highest ambient PM2.5)-vs. below the 10 percentile-were located in neighborhoods
      with higher proportions of Hispanics (20.0% vs. 2.0%), households with an annual
      income of less than $20,000 (26.0% vs. 7.5%), and individuals with less than a
      high school degree (23.2% vs. 5.8%). Our approach can be applied in
      epidemiological studies to estimate exposure modifiers or to characterize
      exposure disparities that are not solely based on ambient concentrations.

PMID- 30242267
TI  - Intra-household agreement of urinary elemental concentrations in Tanzania and
      Kenya: potential surrogates in case-control studies.
AB  - Element deficiencies and excesses play important roles in non-communicable
      disease aetiology. When investigating their roles in epidemiologic studies
      without prospective designs, reverse-causality limits the utility of transient
      biomarkers in cases. This study aimed to investigate whether surrogate
      participants may provide viable proxies by assessing concentration correlations
      within households. We obtained spot urine samples from 245 Tanzanian and Kenyan
      adults (including 101 household pairs) to investigate intra-household
      correlations of urinary elements (As, Ba, Ca, Cd, Co, Cs, Cu, Fe, Li, Mn, Mo, Ni,
      Pb, Rb, S, Se, Sr, Tl, V and Zn) and concentrations (also available for: Bi, Ce,
      Sb, Sn and U) relative to external population-levels and health-based values.
      Moderate-strong correlations were observed for As (r = 0.65), Cs (r = 0.67), Li
      (r = 0.56), Mo (r = 0.57), Se (r = 0.68) and Tl (r = 0.67). Remaining
      correlations were <0.41. Median Se concentrations in Tanzania (29 ug/L) and Kenya
      (24 ug/L) were low relative to 5738 Canadians (59 ug/L). Exceedances (of
      reference 95th percentiles) were observed for: Co, Mn, Mo, Ni and U. Compared to
      health-based values, exceedances were present for As, Co, Mo and Se but
      deficiencies were also present for Mo and Se. For well correlated elements,
      household members in East African settings provide feasible surrogate cases to
      investigate element deficiencies/excesses in relation to non-communicable
      diseases.

PMID- 30242268
TI  - Simulating exposure-related behaviors using agent-based models embedded with
      needs-based artificial intelligence.
AB  - Exposure to a chemical is a critical consideration in the assessment of risk, as
      it adds real-world context to toxicological information. Descriptions of where
      and how individuals spend their time are important for characterizing exposures
      to chemicals in consumer products and in indoor environments. Herein we create an
      agent-based model (ABM) that simulates longitudinal patterns in human behavior.
      By basing the ABM upon an artificial intelligence (AI) system, we create agents
      that mimic human decisions on performing behaviors relevant for determining
      exposures to chemicals and other stressors. We implement the ABM in a computer
      program called the Agent-Based Model of Human Activity Patterns (ABMHAP) that
      predicts the longitudinal patterns for sleeping, eating, commuting, and working.
      We then show that ABMHAP is capable of simulating behavior over extended periods
      of time. We propose that this framework, and models based on it, can generate
      longitudinal human behavior data for use in exposure assessments.

PMID- 30242269
TI  - Sources of clinically significant neonatal intensive care unit phthalate
      exposure.
AB  - In the United States each year, more than 300,000 infants are admitted to
      neonatal intensive care units (NICU) where they are exposed to a chemical
      intensive hospital environment during a developmentally vulnerable period.
      Although multiple studies have demonstrated elevated phthalate biomarkers in NICU
      patients, specific sources of NICU-based phthalate exposure have not been
      identified.In this study, premature newborns with birth weight <1500 g were
      recruited to participate in a prospective environmental health cohort during the
      NICU hospitalization. Exposure to specific NICU equipment was recorded daily
      during the NICU hospitalization. One hundred forty-nine urine specimens from 71
      infants were analyzed for phthalate metabolites using high-performance liquid
      chromatography/tandem mass spectrometry.In initial analyses, exposure to medical
      equipment was directly related to phthalate levels, with DEHP biomarkers 95-132%
      higher for infants exposed to specific medical equipment types compared to those
      without that equipment exposure (p < 0.001-0.023). This association was mirrored
      for clinically relevant phthalate mixtures whether composed of DEHP metabolites
      or not (p = 0.002-0.007). In models accounting for concurrent equipment use,
      exposure to respiratory support was associated with DEHP biomarkers 50-136%
      higher in exposed compared to unexposed infants (p = 0.007-0.036). Phthalate
      mixtures clinically relevant to neurobehavioral development were significantly
      associated with non-invasive respiratory support (p = 0.008-0.026). Feeding
      supplies and intravenous lines were not significantly associated with clinically
      important phthalate mixtures.Respiratory support equipment may be a significant
      and clinically relevant NICU source of phthalate exposure. Although manufacturers
      have altered feeding and intravenous supplies to reduce DEHP exposure, other
      sources of exposure to common and clinically impactful phthalates persist in the
      NICU.

PMID- 30242270
TI  - Enzalutamide treatment for the whole spectrum of CRPC.

PMID- 30242271
TI  - Hierarchical and stage-specific regulation of murine cardiomyocyte maturation by
      serum response factor.
AB  - After birth, cardiomyocytes (CM) acquire numerous adaptations in order to
      efficiently pump blood throughout an animal's lifespan. How this maturation
      process is regulated and coordinated is poorly understood. Here, we perform a
      CRISPR/Cas9 screen in mice and identify serum response factor (SRF) as a key
      regulator of CM maturation. Mosaic SRF depletion in neonatal CMs disrupts many
      aspects of their maturation, including sarcomere expansion, mitochondrial
      biogenesis, transverse-tubule formation, and cellular hypertrophy. Maintenance of
      maturity in adult CMs is less dependent on SRF. This stage-specific activity is
      associated with developmentally regulated SRF chromatin occupancy and
      transcriptional regulation. SRF directly activates genes that regulate sarcomere
      assembly and mitochondrial dynamics. Perturbation of sarcomere assembly but not
      mitochondrial dynamics recapitulates SRF knockout phenotypes. SRF overexpression
      also perturbs CM maturation. Together, these data indicate that carefully
      balanced SRF activity is essential to promote CM maturation through a hierarchy
      of cellular processes orchestrated by sarcomere assembly.

PMID- 30242272
TI  - High-Resolution AMS Dating of Architecture, Boulder Artworks and the Transition
      to Farming at Lepenski Vir.
AB  - The archaeological site of Lepenski Vir is widely known after its remarkable
      stone art sculptures that represent a unique and unprecedented case of Holocene
      hunter-gatherer creativity. These artworks were found largely associated with
      equally unique trapezoidal limestone building floors around their centrally
      located rectangular stone-lined hearths. A debate has raged since the discovery
      of the site about the chronological place of various discovered features. While
      over years different views from that of the excavator about the stratigraphy and
      chronology of the site have been put forward, some major disagreements about the
      chronological position of the features that make this site a key point of
      reference in European Prehistory persist. Despite challenges of re-analyzing the
      site's stratigraphy from the original excavation records, taphonomic problems,
      and issues of reservoir offsets when providing radiocarbon measurements on human
      and dog bones, our targeted AMS (Accelerator Mass Spectrometry) dating of various
      contexts from this site with the application of Bayesian statistical modelling
      allows us to propose with confidence a new and sound chronological framework and
      provide formal estimates for several key developments represented in the
      archaeological record of Lepenski Vir that help us in understanding the
      transition of last foragers to first farmers in southeast Europe as a whole.

PMID- 30242273
TI  - Application of a mechanobiological algorithm to investigate mechanical mediation
      of heterotopic bone in trans-femoral amputees.
AB  - Heterotopic ossification (HO) is the process of bone formation in tissues that
      are not usually osseous. It occurs in 60% of those with blast-related
      amputations. HO can result in reduced range of motion, pain, nerve impingement
      and can affect prosthesis fitting and is caused by a combination of mechanical,
      biological, local and systemic factors. As with normal bone formation and
      remodelling, it is expected that heterotopic bone responds to mechanical stimuli
      and understanding this relationship can give insight into the pathology. The
      objective of this research was to investigate whether a physiological 2D
      computational model that considers both mechanical and biological factors can be
      used to simulate HO in the residual limb of a trans-femoral amputee. The study
      found that characteristic morphologies of HO were reproduced by adjusting the
      loading environment. Significant effects were produced by changing the loading
      direction on the femur; this is potentially associated with different initial
      surgical interventions such as muscle myodesis. Also, initial treatment such as
      negative pressure through a dressing was found to change the shape of heterotopic
      bone.

PMID- 30242274
TI  - Guided Slow Continuous Suspension Film Flow for Mass Production of Submicrometer
      Spherical Particles by Pulsed Laser Melting in Liquid.
AB  - Pulsed laser melting in liquid (PLML) is a technique to fabricate submicrometer
      crystalline spherical particles of various materials by laser irradiation of
      suspended raw particles with random shapes. To fully exploit the unique features
      of PLML-fabricated particles (crystalline and spherical) in practice, a mass
      production PLML technique is required. To this end, the present study develops a
      new slit nozzle that guides the suspension film flow into a non-droplet
      continuous stream with a low flow rate. These two incompatible flow properties
      (continuity and slowness) are difficult to be realized for a liquid jet to free
      space. The suspension film flow was irradiated with a typical laboratory scale
      flash lamp pumping laser at 30 Hz pulse frequency. Only a single flow passage of
      the slit nozzle with a few laser pulse irradiation transformed 95% of the raw
      particles into spherical particles. This spheroidizing ratio exceeded those of
      low-rate drip flow and high-rate cylindrical laminar flow directly jetted into
      free space through a Pasteur pipette nozzle. Extrapolating the data obtained from
      a 20-ml suspension, the average production rate was determined as 195 mg h-1. The
      high spheroidizing ratio and yield through the slit nozzle is attributable to the
      uniquely slow but continuous liquid film flow. The structure of the slit nozzle
      also prevents particles from adhering to the slit wall during continuous laser
      irradiation. Thus, the suspension film flow through the newly developed slit
      nozzle can potentially scale up the PLML technique to mass production.

PMID- 30242275
TI  - Bandgap reduction of photocatalytic TiO2 nanotube by Cu doping.
AB  - We performed the electronic structure calculations of Cu-doped TiO2 nanotubes by
      using density functional theory aided by the Hubbard correction (DFT + U).
      Relative positions of the sub-bands due to the dopants in the band diagram are
      examined to see if they are properly located within the redox interval. The
      doping is found to tune the material to be a possible candidate for the
      photocatalyst by making the bandgap accommodated within the visible and infrared
      range of the solar spectrum. Among several possibilities of the dopant positions,
      we found that only the case with the dopant located at the center of nanotube
      seems preventing from electron-hole recombinations to achieve desired
      photocatalytic activity with n-type behavior.

PMID- 30242276
TI  - Publisher Correction: Concurrent guiding of light and heat by transformation
      optics and transformation thermodynamics via soft matter.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30242277
TI  - Responses of Labile Organic Nitrogen Fractions and Enzyme Activities in eroded
      Mollisols After 8-year Manure Amendment.
AB  - Soil erosion will cause a degradation in soil nitrogen supplying capacity (SNSC)
      and manure amendment is an effective way to restored eroded soils. Both labile
      fractions of soil organic N (SON) and N transformation enzymes are indicators for
      SNSC, but the effect of manure amendments on labile SON fractions and the
      relationship between labile SON fractions and enzyme activities remains unclear.
      In this study, five degrees of erosion were simulated in Mollisols (removal of 0,
      5, 10, 20 and 30 cm of topsoil) to analyse the changes in labile SON fractions
      and nitrogen transformation enzyme activities after 8-year manure amendment. We
      found that soil total N (TN), labile SON fractions and enzyme activities all
      increased after manure amendments. The largest labile SON fraction was particle
      organic nitrogen (POM-N) and the second was light fraction organic nitrogen (LFOM
      N), which accounted >60% for TN in total. Correlation analysis showed that both
      urease and protease activities were significantly correlated with POM-N, LFOM-N,
      microbial biomass N and dissolvable organic N, indicating that both urease and
      protease activities can be used to predict labile SON pools and enzyme activities
      worked similarly in indicating SNSC with labile SON fractions. Altogether, 8-year
      manure amendment could recover SNSC of lightly eroded Mollisols to natural
      levels, i.e. erosion depths at 5 cm and 10 cm; however, it is not able to recover
      SNSC in Mollisols suffering severe erosion.

PMID- 30242279
TI  - Role of PKCepsilon in insulin resistance.

PMID- 30242278
TI  - c-Kit+ Cells in Adult Salivary Glands do not Function as Tissue Stem Cells.
AB  - A rare population of salivary gland cells isolated based on c-Kit
      immunoreactivity are thought to represent tissue stem cells since they exhibit
      the most robust proliferative and differentiation capacity ex vivo. Despite their
      high promise for cell-based therapies aimed at restoring salivary function, the
      precise location and in vivo function of c-Kit+ stem cells remain unclear. Here,
      by combining immunostaining with c-KitCreERT2-based genetic labeling and lineage
      tracing in the adult mouse salivary glands, we show that c-Kit is expressed in a
      relatively large and heterogeneous cell population that consists mostly of
      differentiated cells. Moreover, c-Kit does not mark ductal stem cells that are
      known to express cytokeratin K14. Tracking the fate of in vivo-labeled c-Kit+ or
      that of K14+ cells in spheroid cultures reveals a limited proliferative potential
      for c-Kit+ cells and identifies K14+ cells as the major source of salispheres in
      these cultures. Long-term in vivo lineage tracing studies indicate that although
      c-Kit marks at least two discrete ductal cell lineages, c-Kit+ cells do not
      contribute to the normal maintenance of any other cell lineages. Our results
      indicate that c-Kit is not a reliable marker for salivary gland stem cells, which
      has important implications for salivary gland regenerative therapies.

PMID- 30242280
TI  - Cryo-EM analysis of the T3S injectisome reveals the structure of the needle and
      open secretin.
AB  - The bacterial type III secretion system, or injectisome, is a syringe shaped
      nanomachine essential for the virulence of many disease causing Gram-negative
      bacteria. At the core of the injectisome structure is the needle complex, a
      continuous channel formed by the highly oligomerized inner and outer membrane
      hollow rings and a polymerized helical needle filament which spans through and
      projects into the infected host cell. Here we present the near-atomic resolution
      structure of a needle complex from the prototypical Salmonella Typhimurium SPI-1
      type III secretion system, with local masking protocols allowing for model
      building and refinement of the major membrane spanning components of the needle
      complex base in addition to an isolated needle filament. This work provides
      significant insight into injectisome structure and assembly and importantly
      captures the molecular basis for substrate induced gating in the giant outer
      membrane secretin portal family.

PMID- 30242281
TI  - Mechanistic insights into the host-microbe interaction and pathogen exclusion
      mediated by the Mucus-binding protein of Lactobacillus plantarum.
AB  - Surface adhesins of pathogens and probiotics strains are implicated in mediating
      the binding of microbes to host. Mucus-binding protein (Mub) is unique to gut
      inhabiting lactic acid bacteria; however, the precise role of Mub proteins or its
      structural domains in host-microbial interaction is not well understood. Last two
      domains (Mubs5s6) of the six mucus-binding domains arranged in tandem at the C
      terminus of the Lp_1643 protein of Lactobacillus plantarum was expressed in E.
      coli. Mubs5s6 showed binding with the rat intestinal mucus, pig gastric mucins
      and human intestinal tissues. Preincubation of Mubs5s6 with the Caco-2 and HT-29
      cell lines inhibited the binding of pathogenic enterotoxigenic E. coli cells to
      the enterocytes by 68% and 81%, respectively. Pull-down assay suggested Mubs5s6
      binding to the host mucosa components like cytokeratins, Hsp90 and Laminin.
      Mubs5s6 was predicted to possess calcium and glucose binding sites. Binding of
      Mubs5s6 with these ligands was also experimentally observed. These ligands are
      known to be associated with pathogenesis suggesting Mub might negotiate pathogens
      in multiple ways. To study the feasibility of Mubs5s6 delivery in the gut, it was
      encapsulated in chitosan-sodium tripolyphosphate microspheres with an efficiency
      of 65% and release up to 85% in near neutral pH zone over a period of 20 hours.
      Our results show that Mub plays an important role in the host-microbial cross
      talk and possesses the potential for pathogen exclusion to a greater extent than
      mediated by L. plantarum cells. The functional and technological characteristics
      of Mubs5s6 make it suitable for breaking the host-pathogen interaction.

PMID- 30242283
TI  - Potential targets for the development of new antifungal drugs.
AB  - In recent years, incidences of invasive fungal infections have greatly increased,
      especially in immunosuppressed patients, but most today's antifungal drugs are
      not completely effective due to the development of drug resistance, as well as
      potential toxicity and adverse effects. Consequently, it is imperative to search
      for novel antifungal agents to combat fungal infections. This review will discuss
      the advances in the traditional antifungal therapy, and present an overview of
      novel strategies for the treatment of fungal infections. The papers presented
      here highlight new targets that could be exploited for development of new
      antifungal agents.

PMID- 30242282
TI  - Chemotherapy payload of anti-insoluble fibrin antibody-drug conjugate is released
      specifically upon binding to fibrin.
AB  - Cancer-induced blood coagulation in human tumour generates insoluble fibrin (IF)
      rich cancer stroma in which uneven monoclonal antibody (mAb) distribution reduce
      the potential effectiveness of mAb-mediated treatments. Previously, we developed
      a mAb that reacts only with IF and not with fibrinogen (FNG) or the fibrin
      degradation product (FDP). Although IF, FNG and FDP share same amino acid
      sequences, the mAb is hardly neutralised by FNG and FDP in circulation and
      accumulates in fibrin clots within tumour tissue. Here, we created an antibody
      drug conjugate (ADC) using the anti-IF mAb conjugated with a chemotherapy payload
      (IF-ADC). The conjugate contains a linker severed specifically by plasmin (PLM),
      which is activated only on binding to IF. Imaging mass spectrometry showed the
      substantial intratumour distribution of the payload following the IF-ADC
      injection into mice bearing IF-rich 5-11 xenografts derived from pancreatic
      tumours of LSL-KrasG12D/+; LSL-Trp53R172H/+; Ptf1a-Cre (KPC) mice. IF-ADC
      treatment significantly extended the survival of the KPC mice. These data suggest
      that conjugating chemotherapy drugs to this IF-specific mAb could represent an
      effective means of treating stroma-rich tumours.

PMID- 30242284
TI  - Active particles bound by information flows.
AB  - Self-organization is the generation of order out of local interactions. It is
      deeply connected to many fields of science from physics, chemistry to biology,
      all based on physical interactions. The emergence of collective animal behavior
      is the result of self-organization processes as well, though they involve
      abstract interactions arising from sensory inputs, information processing,
      storage, and feedback. Resulting collective behaviors are found, for example, in
      crowds of people, flocks of birds, and swarms of bacteria. Here we introduce
      interactions between active microparticles which are based on the information
      about other particle positions. A real-time feedback of multiple active particle
      positions is the information source for the propulsion direction of these
      particles. The emerging structures require continuous information flows. They
      reveal frustrated geometries due to confinement to two dimensions and internal
      dynamical degrees of freedom that are reminiscent of physically bound systems,
      though they exist only as nonequilibrium structures.

PMID- 30242287
TI  - Association between HLA-B*5901 and methazolamide-induced Stevens-Johnson
      syndrome/toxic epidermal necrolysis: a systematic review and meta-analysis.
AB  - Methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis
      (SJS/TEN) are life-threatening adverse drug reactions. Based on previous studies,
      HLA genotypes may play an important role in methazolamide-induced SJS/TEN.
      Therefore, to identify the associations between HLA genotypes and methazolamide
      induced cutaneous adverse drug reactions (cADRs) (i.e., SJS/TEN and
      hypersensitivity syndrome), a systematic review and meta-analysis were performed.
      Two studies (one study in Korean and another in Han Chinese) met the inclusion
      criteria. The studies included 13 patients with methazolamide-induced SJS/TEN, 30
      methazolamide-tolerant, and 768 population controls. Associations between HLA
      B*5901, HLA-B*5901-Cw*0102 haplotype, and methazolamide-induced SJS/TEN were
      identified in methazolamide-tolerant and population controls. Overall ORs were
      305.0 (95% CI = 11.3-8, 259.4) in methazolamide-tolerant and 715.3 (95% CI = 83.1
      6,158.5) in population control. In addition, statistically significant
      associations between the HLA-Cw*0102 and methazolamide-induced SJS/TEN were found
      in methazolamide-tolerant (OR = 12.1; 95% CI = 1.3-111.7) and population control
      (OR = 17.5; 95% CI = 3.2-96.6). Since HLA-B*5901 and HLA-B*5901-Cw*0102 haplotype
      are associated with methazolamide-induced SJS/TEN, genetic screening prior to
      methazolamide therapy in Asian populations is warranted.

PMID- 30242285
TI  - Commensal microbiota induces colonic barrier structure and functions that
      contribute to homeostasis.
AB  - The intestinal barrier encompasses structural, permeability and immune aspects of
      the gut mucosa that, when disrupted, may contribute to chronic inflammation.
      Although gnotobiotic studies have demonstrated the effects of microbiota on
      mucosal and systemic immunity, as well as intestinal barrier architecture and
      innate immune characteristics, its impact on barrier function remains unclear. We
      compared germ-free and conventional mice, as well as mice colonized with human
      fecal microbiota that were followed for 21 days post-colonization. Colonic
      barrier structure was investigated by immunohistochemistry, molecular and
      electron microscopy techniques. Permeability was assessed in colon tissue by
      Ussing chambers, and by serum LPS and MDP detection using TLR4- and NOD2-NFkappaB
      reporter assays. Microbiota profile was determined by Illumina 16S rRNA gene
      sequencing. Low dose dextran sodium sulfate was administered to assess microbiota
      induced barrier changes on resistance to colonic injury. Permeability to
      paracellular probes and mucus layer structure resembled that of conventional mice
      by day 7 post-colonization, coinciding with reduced claudin-1 expression and
      transient IL-18 production by intestinal epithelial cells. These post
      colonization adaptations were associated with decreased systemic bacterial
      antigen exposure and reduced susceptibility to intestinal injury. In conclusion,
      commensal colonization promotes physiological barrier structural and functional
      adaptations that contribute to intestinal homeostasis.

PMID- 30242286
TI  - Impaired wound healing in type 1 diabetes is dependent on 5-lipoxygenase
      products.
AB  - Type 1 diabetes is associated with systemic low grade inflammation (LGI). We have
      previously shown that LGI in diabetic mice depends on systemic circulation of
      leukotriene (LTB4) which potentiates the toll-like/IL1beta receptors response in
      macrophages. Impaired wound healing is an important co-morbidity in diabetes, and
      macrophages play a key role in this process. Here, we investigated the role of
      leukotrienes on monocytes and macrophages phenotype and in the impaired wound
      healing in diabetic mice. Type 1 diabetes was induced with streptozotocin in
      129SvE wild-type (WT) and leukotrienes-deficient 5LO-/- (5-lipoxygenase knockout)
      mice. In diabetics, the systemic levels of LTB4, TNF-alpha, IL-6, IL-10, IL-12
      and IFNgamma were increased as well as the frequency of pro-inflammatory
      monocytes (CD11b+Ly6ChighLy6G-) compared to healthy mice. In diabetic 5LO-/-
      mice, these parameters were similar to those in healthy mice. Resident peritoneal
      macrophages from diabetic WT mice showed a classically activated M1-like
      phenotype (high Nos2, Stat and Il12 expression, and nitrite levels). Macrophages
      from diabetic 5LO-/- mice presented alternatively activated M2-macrophages
      markers (high Arg1 and Chi3l3 expression and arginase activity) and when
      stimulated with IL4, enhanced phosphorylated-STAT6. Cutaneous wound healing in
      diabetic WT mice was impaired, which correlated with the decreased frequency of
      M2-macrophages (CD45+F4/80+CD206+) in the lesions. In diabetic 5LO-/- mice, the
      frequency of M2-macrophages in the wound was similar to that in healthy mice,
      suggesting that the impaired healing of diabetic mice depends on 5LO products.
      The inhibition of leukotrienes or antagonism of its receptors could be a
      therapeutic alternative for diabetic patients with impaired healing.

PMID- 30242288
TI  - The chromatin remodeler RSF1 controls centromeric histone modifications to
      coordinate chromosome segregation.
AB  - Chromatin remodelers regulate the nucleosome barrier during transcription, DNA
      replication, and DNA repair. The chromatin remodeler RSF1 is enriched at mitotic
      centromeres, but the functional consequences of this enrichment are not
      completely understood. Shugoshin (Sgo1) protects centromeric cohesion during
      mitosis and requires BuB1-dependent histone H2A phosphorylation (H2A-pT120) for
      localization. Loss of Sgo1 at centromeres causes chromosome missegregation. Here,
      we show that RSF1 regulates Sgo1 localization to centromeres through coordinating
      a crosstalk between histone acetylation and phosphorylation. RSF1 interacts with
      and recruits HDAC1 to centromeres, where it counteracts TIP60-mediated
      acetylation of H2A at K118. This deacetylation is required for the accumulation
      of H2A-pT120 and Sgo1 deposition, as H2A-K118 acetylation suppresses H2A-T120
      phosphorylation by Bub1. Centromeric tethering of HDAC1 prevents premature
      chromatid separation in RSF1 knockout cells. Our results indicate that RSF1
      regulates the dynamics of H2A histone modifications at mitotic centromeres and
      contributes to the maintenance of chromosome stability.

PMID- 30242289
TI  - Steeper structure-function relationship in eyes with than without a parapapillary
      deep-layer microvasculature dropout.
AB  - The degree of visual field (VF) loss can vary widely at a given level of retinal
      nerve fiber layer (RNFL) thickness. The cause of this variability is not fully
      understood. This cross-sectional study investigated whether the presence of
      choroidal microvasculature dropout (MvD) influences on the structure-function
      relationship among glaucomatous eyes. Seventy-one primary open-angle glaucoma
      (POAG) patients with choroidal MvD as determined by optical coherence tomography
      angiography (MvD+ group), and 71 age- and inferotemporal (IT) RNFL thickness
      matched POAG patients without MvD (MvD- group) were included. VF sensitivity
      within the region corresponding to the IT RNFL sector was averaged using the
      total and pattern deviation fields. The slope of log-scale RNFL thickness versus
      VF defect was significantly steeper for the MvD+ than the MvD- group, as
      determined by both total and pattern deviation maps (P = 0.004 and <0.001,
      respectively). Both total and pattern VF deviation were significantly worse in
      the MvD+ than in the MvD- group (P = 0.002 and 0.007, respectively). Same results
      were obtained in subgroup analyses for eyes with thick and thin RNFL thickness
      (all P <= 0.027). These data suggest that parapapillary MvD is associated with
      poorer function of the remaining axons in eyes with POAG.

PMID- 30242291
TI  - Helicobacter pylori infection is not related to increased carotid intima-media
      thickness in general population.
AB  - The aim is to determine whether there is an independent association between Hp
      infection and carotid intima-media thickness (CIMT) in a cross-section
      observational study. Among of 14588 routine health check-up participants, 13770
      subjects underwent the 13C-urea breath test (13C-UBT) and ultrasound measurement
      of CIMT. Traditional atherosclerotic risk factors were also recorded. The ratio
      of increased CIMT in Hp positive group (28.6%) was not significant difference
      compared with Hp negative group (29.7%) (p = 0.164). The HP infection rates was
      no significant difference between increased CIMT (38.4%) and non- increased CIMT
      (39.7%) patients. However, all the traditional atherosclerotic risk factors
      including age, gender, BMI, waistline, total cholesterol, low density lipoprotein
      cholesterol, very low density lipoprotein cholesterol, high density lipoprotein
      cholesterol, triglycerides, free fatty acid, homocysteine, systolic and diastolic
      blood pressure, fasting plasma glucose and C reactive protein were different
      between increased CIMT and non- increased CIMT participants. The odds of Hp
      infection for CIMT risk (OR 0.948; 95% CI 0.879-1.022; P = 0.164) was not higher
      in binary logistic regression analysis even after adjustment for traditional risk
      factors (OR 1.118; 95% CI 0.958-1.306; P = 0.157). Our study found no evidence of
      association between CIMT and HP infection.

PMID- 30242290
TI  - Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with
      Improved Cognitive Age in Humans.
AB  - Advanced age is associated with a decline in cognitive function, likely caused by
      a combination of modifiable and non-modifiable factors such as genetics and
      lifestyle choices. Mounting evidence suggests that humanin and other
      mitochondrial derived peptides play a role in several age-related conditions
      including neurodegenerative disease. Here we demonstrate that humanin
      administration has neuroprotective effects in vitro in human cell culture models
      and is sufficient to improve cognition in vivo in aged mice. Furthermore, in a
      human cohort, using mitochondrial GWAS, we identified a specific SNP (rs2854128)
      in the humanin-coding region of the mitochondrial genome that is associated with
      a decrease in circulating humanin levels. In a large, independent cohort,
      consisting of a nationally-representative sample of older adults, we find that
      this SNP is associated with accelerated cognitive aging, supporting the concept
      that humanin is an important factor in cognitive aging.

PMID- 30242294
TI  - Fast evolution unlocks forbidden communities.

PMID- 30242295
TI  - Emergence of evolutionarily stable communities through eco-evolutionary
      tunnelling.
AB  - Ecological and evolutionary dynamics of communities are inexorably intertwined.
      The ecological state determines the fate of newly arising mutants, and mutations
      that increase in frequency can reshape the ecological dynamics. Evolutionary game
      theory and its extensions within adaptive dynamics have been the mathematical
      frameworks for understanding this interplay, leading to notions such as
      evolutionarily stable states (ESS) in which no mutations are favoured, and
      evolutionary branching points near which the population diversifies. A central
      assumption behind these theoretical treatments has been that mutations are rare
      so that the ecological dynamics has time to equilibrate after every mutation. A
      fundamental question is whether qualitatively new phenomena can arise when
      mutations are frequent. Here, we describe an adaptive diversification process
      that robustly leads to complex ESS, despite the fact that such communities are
      unreachable through a step-by-step evolutionary process. Rather, the system as a
      whole tunnels between collective states over a short timescale. The tunnelling
      rate is a sharply increasing function of the rate at which mutations arise in the
      population. This makes the emergence of ESS communities virtually impossible in
      small populations, but generic in large ones. Moreover, communities emerging
      through this process can spatially spread as single replication units that
      outcompete other communities. Overall, this work provides a qualitatively new
      mechanism for adaptive diversification and shows that complex structures can
      generically evolve even when no step-by-step evolutionary path exists.

PMID- 30242293
TI  - Carotid body removal normalizes arterial blood pressure and respiratory frequency
      in offspring of protein-restricted mothers.
AB  - The aim of this study is to evaluate the short-term and long-term effects
      elicited by carotid body removal (CBR) on ventilatory function and the
      development of hypertension in the offspring of malnourished rats. Wistar rats
      were fed a normo-protein (NP, 17% casein) or low-protein (LP, 8% casein) diet
      during pregnancy and lactation. At 29 days of age, the animals were submitted to
      CBR or a sham surgery, according to the following groups: NP-cbr, LP-cbr, NP
      sham, or LP-sham. In the short-term, at 30 days of age, the respiratory frequency
      (RF) and immunoreactivity for Fos on the retrotrapezoid nucleus (RTN; brainstem
      site containing CO2 sensitive neurons) after exposure to CO2 were evaluated. In
      the long term, at 90 days of age, arterial pressure (AP), heart rate (HR), and
      cardiovascular variability were evaluated. In the short term, an increase in the
      baseline RF (~6%), response to CO2 (~8%), and Fos in the RTN (~27%) occurred in
      the LP-sham group compared with the NP-sham group. Interestingly, the CBR in the
      LP group normalized the RF in response to CO2 as well as RTN cell activation. In
      the long term, CBR reduced the mean AP by ~20 mmHg in malnourished rats. The
      normalization of the arterial pressure was associated with a decrease in the low
      frequency (LF) oscillatory component of AP (~58%) and in the sympathetic tonus to
      the cardiovascular system (~29%). In conclusion, carotid body inputs in
      malnourished offspring may be responsible for the following: (i) enhanced
      respiratory frequency and CO2 chemosensitivity in early life and (ii) the
      production of autonomic imbalance and the development of hypertension.

PMID- 30242296
TI  - Credat Emptor - The Sacrosanct Doctor-Patient Relationship.

PMID- 30242298
TI  - Performance of the Paediatric Index of Mortality 3 and Paediatric Logistic Organ
      Dysfunction 2 Scores in Critically Ill Children.
AB  - INTRODUCTION: The Paediatric Index of  Mortality 3 (PIM 3) and Paediatric
      Logistic Organ Dysfunction 2 (PELOD 2) scores were recently revised. We aimed to
      assess the performance of these scores in a contemporary cohort of critically ill
      children. MATERIALS AND METHODS: This is a single-centre prospective study
      conducted in a multidisciplinary paediatric intensive care unit (PICU).
      Consecutive PICU admissions over 1 year were included and admission PIM 3 and
      PELOD 2 scores were calculated. The performance of each of the scores was
      evaluated by calculating the area under the curve (AUC) of the receiver operating
      characteristic (ROC) and the Hosmer-Lemeshow goodness-of-fit test for the outcome
      of PICU mortality. RESULTS: A total of  570 patient admissions were eligible for
      this study. The median age of patients was 3.1 (interquartile range [IQR]: 0.4,
      8.9 years). Overall median PIM 3 and PELOD 2 scores were 1.2 (IQR: 0.4, 3.2) %
      and 4 (IQR: 2, 7), respectively. The overall mortality rate was 35/570 (6.1%).
      The PIM 3 and PELOD 2 scores had good discrimination for mortality (AUCs 0.88
      [95% confidence interval (CI) 0.85, 0.91] and 0.86 [95% CI 0.83, 0.89],
      respectively). Goodness-of-fit was satisfactory for both scores. Higher PIM 3 and
      PELOD 2 scores were also associated with decreasing ventilator and PICU-free
      days. CONCLUSION: PIM 3 and PELOD 2 scores are robust severity of illness scores
      that are generalisable to a contemporary cohort of critically ill children in
      Singapore.

PMID- 30242297
TI  - Computed Tomography Urography: Comparison of Image Quality and Radiation Dose
      between Single- and Split-Bolus Techniques.
AB  - INTRODUCTION: In this study, we aimed to compare the split-bolus and single-bolus
      computerised tomography (CT) urography and determine if this offers a reduction
      in radiation dose without compromising image quality. MATERIALS AND METHODS: A
      retrospective evaluation was performed on 88 patients undergoing split-bolus CT
      urography and this was compared to a control group of 101 consecutive patients
      undergoing single-bolus CT urography. A radiation dose analysis was performed on
      each subject. Subjects with urinary bladder lesions, hydronephrosis, renal masses
      or cysts >3 cm in diameter were excluded. All images were classified according to
      image quality by 2 consultant radiologists. RESULTS: Opacification of  the renal
      parenchyma, pelvicalyceal system, proximal ureters and urinary bladder were
      comparable between the 2 techniques, whilst image quality of the middle and
      distal third of the ureters was better using the split-bolus technique. The mean
      dose length product (DLP) for the single-bolus technique was 1324.1 mGy-cm,
      whilst that of  the split-bolus technique was 885.7 mGy-cm. The mean effective
      dose reduction was calculated to be 31.1% between the 2 groups. CONCLUSION: The
      split-bolus technique gives a reduced radiation dose without compromising image
      quality. The associated reduction in images is beneficial for data storage and
      reporting efficiency. As such, our department will adopt the split-bolus
      technique for young, low-risk patients.

PMID- 30242292
TI  - Learning deficits in rats overexpressing the dopamine transporter.
AB  - With its capacity to modulate motor control and motivational as well as cognitive
      functions dopamine is implicated in numerous neuropsychiatric diseases. The
      present study investigated whether an imbalance in dopamine homeostasis as
      evident in the dopamine overexpressing rat model (DAT-tg), results in learning
      and memory deficits associated with changes in adult hippocampal neurogenesis.
      Adult DAT-tg and control rats were subjected to the Morris water maze, the radial
      arm maze and a discrimination reversal paradigm and newly generated neurons in
      hippocampal circuitry were investigated post mortem. DAT-tg rats were found to
      exhibit a striking inability to acquire information and deploy spatial search
      strategies. At the same time, reduced integration of adult-born neurons in
      hippocampal circuitry was observed, which together with changes in striatal
      dopamine signalling might explain behavioural deficits.

PMID- 30242299
TI  - Long-Term Morbidities in Children with Critical Illness: Gaps and Opportunities.
AB  - INTRODUCTION: Improved mortality rates in paediatric critical care may come with
      the cost of increased morbidity. Goals of modern paediatric intensive care unit
      (PICU) management should focus on restoring long-term function of paediatric
      critical illness survivors. This review outlines our current knowledge on
      trajectories and risk factors of long-term morbidities in PICU survivors.
      Specifically, we aimed to identify current limitations and gaps in this area so
      as to identify opportunities for future investigations to reduce the burden of
      morbidities in these children. MATERIALS AND METHODS: A review of primary studies
      published in PubMed, EMBASE, and Cochrane databases in the last decade (2008
      2017) describing long-term morbidities in PICU survivors was conducted. RESULTS:
      Children surviving critical illness continue to experience morbidities after
      discharge. A set of risk factors modify their long-term trajectories of recovery,
      with some children achieving their premorbid level of function, while some others
      deteriorate or die. Limitations in current methodologies of morbidity research
      impair our understanding on the causes of these morbidities. Opportunities for
      future endeavours to reduce the burden of these morbidities include identifying
      patients who are more likely to develop morbidities, evaluating the efficacy of
      early rehabilitation, identifying patients who might benefit from tight glycaemic
      control, characterising the optimal nutritional intervention, and improving
      management of increased intracranial pressure. CONCLUSION: Survivors of
      paediatric critical illness experience differing trajectories of recovery from
      morbidities. Future research is needed to expand our repertoire on management
      strategies to improve long-term function in these children.

PMID- 30242300
TI  - Health Technology Disinvestment in Singapore.
AB  - Healthcare decision-makers are constantly challenged by growing healthcare needs
      in tandem with rising healthcare costs. Disinvesting in technologies and
      practices that are "low in value" is one strategy to re-allocate limited
      resources to the most effective, safe and cost-effective technologies. We put
      forward a health technology reassessment framework and examined the opportunities
      and challenges on technology disinvestment in Singapore and deliberated on
      possible solutions. We coordinated and supported a disinvestment programme in 2
      hospitals, 1 specialist centre and 9 primary care institutions in the public
      healthcare sector. The key processes were identifying, prioritising and assessing
      low-value health technologies and practices, disseminating and implementing
      disinvestment recommendations, and post-implementation evaluation. Through case
      studies, we explored the barriers and enablers to the success of the programme.
      One of the barriers to disinvestment included difficulty in demonstrating a lack
      of benefit of in-use technologies from published studies. Differing viewpoint and
      priority might preclude a healthcare leader's support in such initiatives and
      that posed an unsurmountable hurdle. On the other hand, engaging the stakeholder
      throughout the evidence review process and striking a balance between rigour and
      timeliness of review were likely to assure success. Lastly, monitoring the impact
      on resources and patient outcomes can be diverse and methods need to be
      developed. Understanding barriers and enablers in health technology disinvestment
      can translate into improved opportunities for eliminating and minimising resource
      wastage.

PMID- 30242301
TI  - Pancreatic Haemangioma: An Unusual Case of Massive Upper Gastrointestinal
      Bleeding with Clinical and Radiological Correlation of the Literature and
      Recommendations.

PMID- 30242302
TI  - Oculopharyngeal Muscular Dystrophy in Singapore: Not So Rare.

PMID- 30242303
TI  - Danger in Shopping Centres - A Study on Escalator-Related Injuries in Children in
      Singapore.

PMID- 30242305
TI  - Oral Contraceptive Progestin and Estrogen Use and Increases in Breast, Ovarian,
      and Endometrial Cancers.

PMID- 30242304
TI  - Value-Based Payments and Inaccurate Risk Adjustment-Who Is Harmed?

PMID- 30242307
TI  - Need for Reassessment of Early Transpyloric Feeding in Preterm Infants.

PMID- 30242306
TI  - Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for
      Patients With Metastatic Triple-Negative Breast Cancer: A Phase 1 Study.
AB  - Importance: Atezolizumab (anti-programmed cell death ligand 1 [PD-L1]) is well
      tolerated and clinically active in multiple cancer types. Its safety and clinical
      activity in metastatic triple-negative breast cancer (mTNBC) has not been
      reported. Objective: To evaluate the safety, clinical activity, and biomarkers
      associated with the use of single-agent atezolizumab in patients with mTNBC.
      Design, Setting, and Participants: Women with mTNBC (defined by investigator
      assessment) were enrolled between January 2013 and February 2016 in a multicohort
      open-label, phase 1 study at US and European academic medical centers. Median
      follow-up was 25.3 months (range, 0.4-45.6 months). Eligible patients regardless
      of line of therapy had measurable disease by Response Evaluation Criteria in
      Solid Tumors, version 1.1; Eastern Cooperative Oncology Group performance status
      of 0 to 1; and a representative tumor sample for assessment of immune cell (IC)
      PD-L1 expression. Interventions: Atezolizumab was given intravenously every 3
      weeks until unacceptable toxic effects or loss of clinical benefit. Main Outcomes
      and Measures: Primary outcome was safety and tolerability. Activity and
      exploratory outcomes included objective response rate (ORR), duration of
      response, progression-free survival (PFS), and overall survival (OS). Outcomes
      were assessed in all patients and in key patient subgroups. Results: Among 116
      evaluable patients (median age, 53 years [range, 29-82 years]), treatment-related
      adverse events occurred in 73 (63%); 58 (79%) were grade 1 to 2. Most adverse
      events occurred within the first treatment year. The ORRs were numerically higher
      in first-line (5 of 21 [24%]) than in second-line or greater patients (6 of 94
      [6%]). Median duration of response was 21 months (range, 3 to >=38 months).
      Median PFS was 1.4 (95% CI, 1.3-1.6) months by RECIST and 1.9 (95% CI, 1.4-2.5)
      months by irRC. In first-line patients, median OS was 17.6 months (95% CI, 10.2
      months to not estimable). Patients with PD-L1 expression of at least 1% tumor
      infiltrating ICs had higher ORRs and longer OS (12% [11 of 91]; 10.1 [95% CI, 7.0
      13.8] months, respectively) than those with less than 1% ICs (0 of 21; 6.0 [95%
      CI, 2.6-12.6] months, respectively). High levels of ICs (>10%) were independently
      associated with higher ORRs and longer OS. Conclusions and Relevance: Single
      agent atezolizumab was well tolerated and provided durable clinical benefit in
      patients with mTNBC with stable or responding disease and in earlier lines of
      treatment. Trial Registration: ClinicalTrials.gov identifier: NCT01375842.

PMID- 30242308
TI  - Challenges in Adopting Level 1 Evidence for Multiparametric Magnetic Resonance
      Imaging as a Biomarker for Prostate Cancer Screening.

PMID- 30242309
TI  - Association of Leucine-Rich Glioma Inactivated Protein 1, Contactin-Associated
      Protein 2, and Contactin 2 Antibodies With Clinical Features and Patient-Reported
      Pain in Acquired Neuromyotonia.
AB  - Importance: Although acquired autoimmune neuromyotonia (NMT) is associated with
      voltage-gated potassium channel (VGKC)-complex antibodies, to date there has been
      no systematic study of autoantibodies to the specific antigens leucine-rich
      glioma inactivated protein 1 (LGI1), contactin-associated protein 2 (CASPR2), and
      contactin 2 together with the full clinical syndrome, particularly pain and
      autonomic and central nervous system involvement. Objectives: To study the full
      spectrum of clinical features and serum autoantibodies in patients with NMT,
      including the effects of pain on quality of life. Design, Setting, and
      Participants: A cohort study of clinical features and serologic testing in 38
      patients with electrophysiologically-confirmed NMT, reviewed clinically between
      February 2007 and August 2009, in the Universities of Sydney and Kagoshima and
      followed up across 2 to 4 years. Association of NMT with quality of life was
      researched in an independent, patient-led, online pain survey conducted from
      April 2012 to May 2012. Serologic analyses were performed in 2012, and final data
      analysis was performed in 2016. Main Outcomes and Measures: Clinical data and
      scores on the modified Rankin Scale (mRS), which measures disability on a range
      of 0 to 6, with 0 indicating normal and 6 indicating death, before and after
      treatments were combined with CASPR2, LGI1, and contactin 2 antibody status.
      Results: Among the 38-person NMT cohort, 25 (65.8%) were male and the median
      (range) age was 55 (12-85) years. Twenty-three (60.5%) were Japanese and 15
      (39.5%) were of white race/ethnicity. Symptomatic treatments (mainly
      antiepileptic drugs) were used in most patients with mild disease (12 patients
      with mRS <3), whereas immunotherapies were successful in most patients with mRS
      scores greater than 2. Autoantibodies to VGKC-complex antigens (17 patients
      [45%]), bound to CASPR2 (5 [13%]), contactin 2 (5 patients, 1 with CASPR2 [13%]),
      LGI1 (2 [5%]), or both LGI1 and CASPR2 (6 [16%]). The last group of 6 patients
      had high mRS scores (mean [SD], 3.8 [1.7]), thymoma (4 patients), pain (5
      patients), autonomic (6 patients) and sleep (5 patients) disturbance, suggesting
      Morvan syndrome. The 56 responders to the independent patient-led survey reported
      pain that could be severe, anatomically widespread, and that often resulted in
      unemployment, domestic problems, and poor quality of life. Conclusions and
      Relevance: The cohort study detailed underrecognized aspects of the clinical and
      serologic spectrum of NMT. The heterogeneity of clinical features and of specific
      antibodies limit associations, but the common existence of thymoma, pain, and
      autonomic and central nervous system features, often with both LGI1 and CASPR2
      antibodies, should be better recognized to more completely address the range of
      comorbidities and consequences of the disease regarding quality of life.

PMID- 30242311
TI  - Oral Contraceptive Progestin and Estrogen Use and Increases in Breast, Ovarian,
      and Endometrial Cancers-Reply.

PMID- 30242310
TI  - Epidural Spinal Cord Stimulation Training and Sustained Recovery of
      Cardiovascular Function in Individuals With Chronic Cervical Spinal Cord Injury.

PMID- 30242312
TI  - Percutaneous Radiofrequency Lower Face and Neck Tightening Technique.

PMID- 30242313
TI  - Association of Hair Loss With Health Utility Measurements Before and After Hair
      Transplant Surgery in Men and Women.
AB  - Importance: Androgenetic alopecia is a highly prevalent condition across both
      sexes and can be surgically corrected through hair transplant. Health utility
      scores, which represent quantitative estimates of individual preferences for a
      given state of health, are a measure of health-related quality of life. The
      health utility scores for sex-specific alopecia and the posttransplant state have
      not previously been quantified. Objective: To obtain health utility measurements
      for the objective assessment of sex-specific alopecia and hair transplant surgery
      and to analyze layperson perception of alopecia compared with other chronic
      health conditions. Design, Setting, and Participants: A prospective clinical
      study was conducted from August 1 to December 31, 2017, at the Harvard Decision
      Science Laboratory. Adult casual observers (n = 308) completed an internet-based
      health utility questionnaire. Health states were presented using still patient
      images and a description of 5 health states, including monocular blindness,
      binocular blindness, male alopecia, female alopecia, and male posttransplant
      state. Main Outcomes and Measures: Health utility measures of sex-specific
      alopecia, posttransplant state, and monocular and binocular blindness were
      measured by visual analog scale (VAS), standard gamble (SG), and time trade-off
      (TTO) in quality-adjusted life-years (QALYs). Groups were analyzed with 1-way
      analysis of variance and post hoc Tukey pairwise comparison. Results: The 308
      participants included 157 (51.0%) women with a mean (SD) age of 30.8 (13.5)
      years. Mean (SD) health utility measures included 0.85 (0.18) QALYs for the VAS,
      0.93 (0.17) QALYs for the SG, and 0.93 (0.17) QALYs for the TTO in male alopecia;
      0.83 (0.19) QALYs for the VAS, 0.92 (0.17) QALYs for the SG, and 0.91 (0.18)
      QALYs for the TTO in female alopecia; and 0.93 (0.11) QALYs for the VAS, 0.95
      (0.15) QALYs for the SG, and 0.95 (0.16) QALYs for the TTO in a man in the
      posttransplant state. The mean (SD) health utility of monocular blindness was
      0.76 (0.17) QALYs for the VAS, 0.87 (0.21) QALYs for the SG, and 0.86 (0.20)
      QALYs for the TTO. The health utility score for the posttransplant state was
      significantly improved compared with the health utility score for alopecia in
      both sexes (female VAS: +0.10 [95% CI, 0.06-0.14; P < .001]; male VAS, +0.08 [95%
      CI, 0.04-0.12; P < .001]). Hair loss in women and men demonstrated significantly
      lower QALYs on the VAS compared with the posttransplant state (female: -0.10 [95%
      CI, -0.14 to -0.06; P < .001]; male: -0.08 [95% CI, -0.12 to -0.04; P < .001]).
      Conclusions and Relevance: Alopecia has a meaningful negative influence on health
      utility measures in both sexes. Hair transplant surgery significantly increases
      health utility measures compared with untreated alopecia in both sexes as rated
      among layperson observers. Level of Evidence: NA.

PMID- 30242314
TI  - A Lesion on the Scalp.

PMID- 30242315
TI  - Use of Medical Scribes to Reduce Documentation Burden: Are They Where We Need to
      Go With Clinical Documentation?

PMID- 30242317
TI  - Memorial Day Reflections-The Invisible Enemy.

PMID- 30242318
TI  - Screening and Management of High Blood Pressure in Children and Adolescents.

PMID- 30242316
TI  - Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic
      Review and Meta-analysis.
AB  - Importance: Immune checkpoint inhibitors (ICIs) are now a mainstay of cancer
      treatment. Although rare, fulminant and fatal toxic effects may complicate these
      otherwise transformative therapies; characterizing these events requires
      integration of global data. Objective: To determine the spectrum, timing, and
      clinical features of fatal ICI-associated toxic effects. Design, Setting, and
      Participants: We retrospectively queried a World Health Organization (WHO)
      pharmacovigilance database (Vigilyze) comprising more than 16 000 000 adverse
      drug reactions, and records from 7 academic centers. We performed a meta-analysis
      of published trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti
      cytotoxic T lymphocyte antigen-4 (CTLA-4) to evaluate their incidence using data
      from large academic medical centers, global WHO pharmacovigilance data, and all
      published ICI clinical trials of patients with cancer treated with ICIs
      internationally. Exposures: Anti-CTLA-4 (ipilimumab or tremelimumab), anti-PD-1
      (nivolumab, pembrolizumab), or anti-PD-L1 (atezolizumab, avelumab, durvalumab).
      Main Outcomes and Measures: Timing, spectrum, outcomes, and incidence of ICI
      associated toxic effects. Results: Internationally, 613 fatal ICI toxic events
      were reported from 2009 through January 2018 in Vigilyze. The spectrum differed
      widely between regimens: in a total of 193 anti-CTLA-4 deaths, most were usually
      from colitis (135 [70%]), whereas anti-PD-1/PD-L1-related fatalities were often
      from pneumonitis (333 [35%]), hepatitis (115 [22%]), and neurotoxic effects (50
      [15%]). Combination PD-1/CTLA-4 deaths were frequently from colitis (32 [37%])
      and myocarditis (22 [25%]). Fatal toxic effects typically occurred early after
      therapy initiation for combination therapy, anti-PD-1, and ipilimumab monotherapy
      (median 14.5, 40, and 40 days, respectively). Myocarditis had the highest
      fatality rate (52 [39.7%] of 131 reported cases), whereas endocrine events and
      colitis had only 2% to 5% reported fatalities; 10% to 17% of other organ-system
      toxic effects reported had fatal outcomes. Retrospective review of 3545 patients
      treated with ICIs from 7 academic centers revealed 0.6% fatality rates; cardiac
      and neurologic events were especially prominent (43%). Median time from symptom
      onset to death was 32 days. A meta-analysis of 112 trials involving 19 217
      patients showed toxicity-related fatality rates of 0.36% (anti-PD-1), 0.38% (anti
      PD-L1), 1.08% (anti-CTLA-4), and 1.23% (PD-1/PD-L1 plus CTLA-4). Conclusions and
      Relevance: In the largest evaluation of fatal ICI-associated toxic effects
      published to date to our knowledge, we observed early onset of death with varied
      causes and frequencies depending on therapeutic regimen. Clinicians across
      disciplines should be aware of these uncommon lethal complications.

PMID- 30242319
TI  - Is the Association of Retinal Venous Malformations With Venous Malformations of
      the Brain Clinically Meaningful?

PMID- 30242320
TI  - Pediatric Laryngeal Expression and Surgical Treatment of IgG4-Related Disease.

PMID- 30242321
TI  - Association of the Patient Protection and Affordable Care Act With Insurance
      Coverage for Head and Neck Cancer in the SEER Database.
AB  - Importance: Patients with head and neck squamous cell cancer (HNSCC) are often
      uninsured or underinsured at the time of their diagnosis. This access to care has
      been shown to influence treatment decisions and survival outcomes. Objective: To
      examine the association of the Patient Protection and Affordable Care Act (ACA)
      health care legislation with rates of insurance coverage and access to care among
      patients with HNSCC. Design, Setting, and Participants: Prospectively gathered
      data from the Surveillance, Epidemiology, and End Results (SEER) database were
      used to examine rates of insurance coverage and access to care among 89 038
      patients with newly diagnosed HNSCC from January 2007 to December 2014. Rates of
      insurance were compared between states that elected to expand Medicaid coverage
      in 2014 and states that opted out of the expansion. Statistical analysis was
      performed from January 1, 2007, to December 31, 2014. Main Outcomes and Measures:
      Rates of insurance coverage and disease-specific and overall survival. Results:
      Among 89 038 patients newly diagnosed with HNSCC (29 384 women and 59 654 men;
      mean [SD] age, 59.8 [7.6] years), there was an increase after implementation of
      the ACA in the percentage of patients enrolled in Medicaid (16.2% after vs 14.8%
      before; difference, 1.4%; 95% CI, 1.1%-1.7%) and private insurance (80.7% after
      vs 78.9% before; difference, 1.8%; 95% CI, 1.2%-2.4%). In addition, there was a
      large decrease in the rate of uninsured patients after implementation of the ACA
      (3.0% after vs 6.2% before; difference, 3.2%; 95% CI, 2.9%-3.5%). This decrease
      in the rate of uninsured patients and the associated increases in Medicaid and
      private insurance coverage were only different in the states that adopted the
      Medicaid expansion in 2014. No survival data are available after implementation
      of the ACA, but prior to that point, from 2007 to 2013, uninsured patients had
      reduced 5-year overall survival (48.5% vs 62.5%; difference, 14.0%; 95% CI, 12.8%
      15.2%) and 5-year disease-specific survival compared with insured patients (56.6%
      vs 72.2%; difference, 15.6%; 95% CI, 14.0%-17.2%). Conclusions and Relevance:
      Access to health care for patients with HNSCC was improved after implementation
      of the ACA, with an increase in rates of both Medicaid and private insurance and
      a 2-fold decrease in the rate of uninsured patients. These outcomes were
      demonstrated only in states that adopted the Medicaid expansion in 2014.
      Uninsured patients had poorer survival outcomes.

PMID- 30242322
TI  - Neuropsychological Outcomes of Children 1 Year After Pediatric Cardiac Arrest:
      Secondary Analysis of 2 Randomized Clinical Trials.
AB  - Importance: Little is known about neuropsychological outcomes of children who
      survived pediatric cardiac arrest (CA). Objective: To describe the
      neuropsychological outcomes of CA survivors enrolled in the Therapeutic
      Hypothermia After Pediatric Cardiac Arrest In-Hospital (THAPCA-IH) and Out-of
      Hospital (THAPCA-OH) trials and compare the results with the primary outcome
      measure for these trials. Design, Setting, and Participants: Secondary analysis
      of 222 CA survivors aged 1 to 18 years who received chest compressions for 2
      minutes or more, remained comatose and required mechanical ventilation after
      return of circulation, and were enrolled in targeted temperature-management
      trials from 41 pediatric intensive care units. Data were collected from September
      3, 2009, to February 3, 2016, and analyzed from March 10, 2017, to April 20,
      2018. Main Outcomes and Measures: The Vineland Adaptive Behavior Scales, Second
      Edition (VABS-II), a standardized measure of neurobehavioral functioning based on
      caregiver report (age-corrected mean [SD] scores = 100 [15]), was used to
      evaluate pre-CA functioning within 24 hours after enrollment; VABS-II<70
      indicated significant developmental delays; VABS-II and neuropsychological
      testing were completed 1 year after CA. Neuropsychological testing included the
      Mullen Scales of Early Learning (Mullen) for children younger than 6 years and
      the Wechsler Abbreviated Scale of Intelligence (WASI) and neuropsychological
      measures of attention, memory, processing speed, and executive functioning for
      older children. Results: Of 160 participants who completed neuropsychological
      testing, 96 (60.0%) were male; the median (interquartile range [IQR]) age was 2.5
      years (1.3-6.1 years). Ninety-six (60.0%) were white, 41 (25.6%) were black, and
      23 (14.4%) were of other/unknown race; 343 (21.2%) were Hispanic or Latino; 119
      (74.4%) were non-Hispanic or Latino; and 7 (4.4%) were of unknown ethnicity. One
      hundred fourteen participants (71.2%) were classified as having favorable
      outcomes (VABS-II >=70). Impairments (>2 SD below the mean for age) across
      neuropsychological measures ranged from 7% to 61%. Correlations between global
      cognitive and VABS-II scores were strong for younger children (Mullen, r = 0.69
      0.87) but moderate for older children (r = 0.21-0.54 for the WASI). Of 111
      children with favorable outcomes on VABS-II, 25.2% had global cognitive
      impairment and 30 of 35 older children (85.7%) had selective neuropsychological
      deficits. Conclusions and Relevance: In this prospectively evaluated cohort of
      pediatric CA survivors who were initially comatose, although 71.2% were
      classified as having favorable outcomes, significant neuropsychological deficits
      were identified in pediatric CA survivors who were classified as having favorable
      outcomes. The findings provide clinicians with a greater understanding of the
      spectrum of neuropsychological outcomes of pediatric CA survivors and the complex
      relationship between standardized caregiver-reported functional outcome measures
      incorporated in clinical trials and performance-based neuropsychological
      assessments.

PMID- 30242323
TI  - Industry Payments to Physicians and the Public's Right to Know About Them.

PMID- 30242324
TI  - Ophthalmology Patient Perceptions of Open Payments Information.
AB  - Importance: Since 2014, medical industry payment data to physicians have been
      public via the Open Payments database. Patient opinions regarding these data help
      us to understand concerns and policymakers to improve reporting mechanisms for
      such payments. Objective: To assess patient perceptions of Open Payments
      information. Design, Setting, and Participants: This cross-sectional,
      questionnaire-based study was conducted in 3 ophthalmology clinic sites of an
      academic institution in Manhattan, New York City, New York. All patients older
      than 18 years who were waiting for appointments were eligible. Data were
      collected from January to June 2016 and analyzed from June to September 2016.
      Exposures: Participants answered 27 questions about the Open Payments database in
      English or Spanish. Demographic information was also collected. Main Outcomes and
      Measures: Key questionnaire results included patient awareness of the Open
      Payments database and perceptions of physicians' financial relationships.
      Cronbach alpha validation of the survey was performed, and Poisson multivariable
      regression analysis was performed to evaluate the association between patient
      characteristics and responses. Results: A total of 407 individuals participated.
      The mean (SD) age of study participants was 58.8 (17.9) years, and 220 (54.2%)
      were women. Of these, 30 (7.3% [95% CI, 5.1%-19.4%]) were aware of the Open
      Payments database, and 109 (26.8% [95% CI, 24.8%-34.0%]) planned to access it.
      More than half (n = 212; 53.5% [95% CI, 48.6%-58.5%]) wanted to know if their
      physician receives industry payments. Regarding payments of any kind valuing
      $100, 161 (41.9% [95% CI, 37.0%-46.9%]) disapproved. Similarly, 178 (45.8% [95%
      CI, 40.8%-50.7%]) disapproved of $500 payments, and 221 (57.0% [95% CI, 52.0%
      61.9%]) disapproved of $25 000 payments. Poisson multivariable regression
      analysis demonstrated that participants who took the survey in Spanish were 38%
      more likely to approve of physicians receiving payments than were those who took
      the survey in English (incidence rate ratio [IRR], 1.38 [95% CI, 1.19-1.59]; P <
      .001). For every 1 year of age, the likelihood of approval for a physician
      receiving payments decreased by 1% (IRR, 0.995 [95% CI, 0.99-1.00]; P = .007).
      Participants with graduate degrees were 20% less likely to approve of physicians
      receiving payments, compared with those with less than a high school degree (IRR,
      0.80 [95% CI, 0.66-0.97]; P = .02). Conclusions and Relevance: If the survey is
      validated, and if these results are generalizable outside of the 3 academic
      centers in ophthalmology surveyed, the findings suggest that many patients
      disapprove of physicians receiving payments from industry. However, few patients
      had accessed the Open Payments database or planned to access it. Further
      investigation is required to determine if these results can be generalized for
      other settings.

PMID- 30242325
TI  - Association of Acute Endophthalmitis With Intravitreal Injections of
      Corticosteroids or Anti-Vascular Growth Factor Agents in a Nationwide Study in
      France.
AB  - Importance: The number of patients affected by retinal diseases treated with
      intravitreal injections (IVTs) has resulted in a rapidly growing number of
      procedures. One of the worst complications after these injections is
      endophthalmitis. Objective: To evaluate the incidence of acute endophthalmitis
      after IVTs of corticosteroids or anti-vascular endothelial growth factor (anti
      VEGF) agents. Design, Setting, and Participants: This population-based cohort
      study included patients undergoing IVTs from January 1, 2012, through December
      31, 2015, in France. Data were acquired from the French medical-administrative
      database (Systeme National d'Information Inter-Regime de l'Assurance Maladie),
      which collects hospitalization discharge abstracts and out-of-hospital care
      information for the whole country. Data were analyzed from March through July
      2017. Exposures: Intravitreal injections of corticosteroid or anti-VEGF agents.
      Main Outcomes and Measures: Incidence of acute endophthalmitis within 6 weeks
      after IVT by means of billing codes from a national database. Results: During the
      study period, 1 811 977 IVTs of corticosteroids or anti-VEGF agents performed on
      254 927 patients (60.4% female; median age, 79 years [interquartile range, 70-85
      years]) were analyzed. A total of 444 acute endophthalmitis cases (crude
      incidence, 0.0245%) were recorded. In multivariable analysis, which did not
      include adjustment for when the endophthalmitis occurred during the study period,
      the risk of endophthalmitis was lower in male patients (incidence rate ratio
      [IRR], 0.78; 95% CI, 0.63-0.96; P = .02), higher for corticosteroids than for
      anti-VEGF agents (IRR, 3.21; 95% CI, 2.33-4.44; P < .001), and higher for
      nonprefilled syringes of anti-VEGF medications than prefilled syringes for
      ranibizumab (IRR, 1.63; 95% CI, 1.15-2.30) and aflibercept (IRR, 1.82; 95% CI,
      1.25-2.66; P < .001). Conclusions and Relevance: The findings from this study of
      a nationwide database appear to have confirmed the low incidence rate of acute
      endophthalmitis after IVTs of corticosteroids or anti-VEGF agents. Although an
      association may not necessarily indicate a cause and effect, the risk for acute
      endophthalmitis after IVTs appeared to be higher for corticosteroids compared
      with anti-VEGF agents, while a lower risk of endophthalmitis appeared to be found
      with prefilled syringes of anti-VEGF medications.

PMID- 30242326
TI  - Potential Benefits of Inhaled Nitric Oxide in Pulmonary Hypertension With
      Hypoplasia in Premature Neonates-Reply.

PMID- 30242327
TI  - A Parathyroid Hemangioma of the Retropharynx.

PMID- 30242328
TI  - Influence of Varying Quantitative Fecal Immunochemical Test Positivity Thresholds
      on Colorectal Cancer Detection: A Community-Based Cohort Study.
AB  - Background: The fecal immunochemical test (FIT) is commonly used for colorectal
      cancer (CRC) screening. Despite demographic variations in stool hemoglobin
      concentrations, few data exist regarding optimal positivity thresholds by age and
      sex. Objective: To identify programmatic (multitest) FIT performance
      characteristics and optimal FIT quantitative hemoglobin positivity thresholds in
      a large, population-based, screening program. Design: Retrospective cohort study.
      Setting: Kaiser Permanente Northern and Southern California. Participants: Adults
      aged 50 to 75 years who were eligible for screening and had baseline quantitative
      FIT results (2013 to 2014) and 2 years of follow-up. Nearly two thirds (411 241)
      had FIT screening in the previous 2 years. Measurements: FIT programmatic
      sensitivity for CRC and number of positive test results per cancer case detected,
      overall and by age and sex. Results: Of 640 859 persons who completed a baseline
      FIT and were followed for 2 years, 481 817 (75%) had at least 1 additional FIT
      and 1245 (0.19%) received a CRC diagnosis. Cancer detection (programmatic
      sensitivity) increased at lower positivity thresholds, from 822 in 1245 (66.0%)
      at 30 ug/g to 925 (74.3%) at 20 ug/g and 987 (79.3%) at 10 ug/g; the number of
      positive test results per cancer case detected increased from 43 at 30 ug/g to 52
      at 20 ug/g and 85 at 10 ug/g. Reducing the positivity threshold from 20 to 15
      ug/g would detect 3% more cancer cases and require 23% more colonoscopies. At the
      conventional FIT threshold of 20 ug/g, programmatic sensitivity decreased with
      increasing age (79.0%, 73.4%, and 68.9% for ages 50 to 59, 60 to 69, and 70 to 75
      years, respectively; P = 0.009) and was higher in men than women (77.0% vs.
      70.6%; P = 0.011). Limitation: Information on advanced adenoma was lacking.
      Conclusion: Increased cancer detection at lower positivity thresholds is
      counterbalanced by substantial increases in positive tests. Tailored thresholds
      may provide screening benefits that are more equal among different demographic
      groups, depending on local resources. Primary Funding Source: National Cancer
      Institute.

PMID- 30242329
TI  - Coagulation Test Interpretation in a Patient Taking Direct Oral Anticoagulant
      Therapy.

PMID- 30242330
TI  - Atypical Infraglottic Lesion.

PMID- 30242331
TI  - Recurrent Bilateral Periorbital Swelling.

PMID- 30242334
TI  - Correction of Potential Conflicts of Interest Disclosures, Author Affiliation,
      and Role of Funder.

PMID- 30242332
TI  - Ultrasonographic Evaluation of Upper Airway Structures in Children With
      Obstructive Sleep Apnea.
AB  - Importance: Adenotonsillar hypertrophy is an important cause of obstructive sleep
      apnea (OSA) in children. However, residual OSA and abnormal polysomnographic
      findings have been reported in up to 75% of cases after adenotonsillectomy. Other
      anatomical and functional factors that influence upper airway structures,
      including the lateral pharyngeal wall, have rarely been studied in children with
      OSA. Objective: To determine whether the upper airway structures can be evaluated
      using head and neck ultrasonography and if there is an association between the
      ultrasonographic measurements for these structures and severity of OSA seen on
      polysomnography in children. Design, Setting, and Participants: Prospective,
      single-center, observational study of 82 children younger than 18 years with a
      diagnosis of sleep-disordered breathing (20 with primary snoring, 62 with OSA, as
      determined by the apnea-hypopnea index) and admitted to a tertiary teaching
      hospital for adenotonsillectomy. Exposures: Ultrasonography and polysomnography.
      Main Outcomes and Measures: Ultrasonographic measurements of upper airway
      structures. Results: Of the 82 children studied, 62 (76%) were boys; mean (SD)
      age, 7.7 (6.2). There was no significant difference found in tonsillar dimensions
      or volume between the children with OSA and those with primary snoring. However,
      the mean (SD) total lateral pharyngeal wall and the total neck thicknesses at the
      retropalatal level were both greater in children with OSA than in those with
      primary snoring at rest (24.9 [4.4] mm vs 21.3 [2.6] mm; difference, 3.61 mm; 95%
      CI of difference, 1.48-5.74 mm for lateral pharyngeal wall; and 59.9 [14.4] mm vs
      49.9 [11.2] mm; difference, 10.9 mm, 95% CI of difference, 3.8-17.9 mm for the
      total neck). Conclusions and Relevance: Estimated tonsillar volume measured using
      ultrasonography had no relationship with the apnea-hypopnea index in childhood
      sleep-disordered breathing. However, the lateral pharyngeal wall was
      significantly thicker in children with OSA than in those with primary snoring at
      rest.

PMID- 30242333
TI  - Association of Cadmium and Lead Exposure With the Incidence of Contrast
      Sensitivity Impairment Among Middle-aged Adults.
AB  - Importance: Contrast sensitivity (CS) is an important indicator of visual
      function that affects daily life, including mobility, visually intensive tasks,
      safety, and autonomy. Understanding the risk factors for CS impairment could
      prevent decreases in visual function. Objective: To determine the incidence of
      and factors associated with CS impairment in a large cohort. Design, Setting, and
      Participants: The Beaver Dam Offspring Study is an ongoing longitudinal cohort
      study of aging involving adults in Beaver Dam, Wisconsin. Participants who were
      free of CS impairment in both eyes at baseline were included (N = 1983). Baseline
      data collection occurred from June 8, 2005, through August 4, 2008, when the
      participants ranged from 21 to 84 years of age. Two follow-up examinations
      occurred at 5-year intervals: one was conducted between July 12, 2010, and March
      21, 2013, and the other between July 1, 2015, and November 13, 2017. Data
      analysis was performed from November 27, 2017, to February 27, 2018. Main
      Outcomes and Measures: Contrast sensitivity testing was conducted with Pelli
      Robson letter sensitivity charts, and incident impairment was defined as a log CS
      score less than 1.55 in either eye at any follow-up examination. Cadmium and lead
      levels were measured in whole blood with inductively coupled plasma mass
      spectrometry. Associations between baseline characteristics and CS impairment
      incidence were examined using Cox proportional hazard models and quantified as
      hazard ratios (HRs) with 95% CI. Results: Of the 1983 participants included, 1028
      (51.8%) were female and 955 (48.2%) were male, with a mean (SD) age of 48 (9.3)
      years. The 10-year cumulative incidence of CS impairment was 24.8% (95% CI, 22.9
      26.8), similar in women (24.9%) and men (24.6%), and highest in the oldest age
      group (65-84 years) at 66.3%. In multivariable models, cadmium level in the
      highest quintile (HR, 1.35; 95% CI, 1.02-1.78), older age (HR, 1.36; 95% CI, 1.25
      1.47), larger waist circumference (HR, 1.06; 95% CI, 1.01-1.11), and more plaque
      sites (1-3 sites: HR, 1.43; 95% CI, 1.07-1.92; 4-6 sites: HR, 2.75; 95% CI, 1.26
      6.05) were among the factors associated with increased risk, while male sex (HR,
      0.77; 95% CI, 0.60-0.98) and any alcohol consumption (HR, 0.61; 95% CI, 0.43
      0.88) were associated with decreased risk. Results were similar when smoking
      status replaced cadmium exposure in the models. Lead level was not associated
      with increased risk. Conclusions and Relevance: This study's findings suggest
      that incident CS impairment was common in the 10-year follow-up, with cadmium,
      but not lead, exposure associated with increased risk. The associations of
      diminished CS with other modifiable risk factors found appear to imply that
      changes in behavior may reduce future incidence of CS impairment.

PMID- 30242336
TI  - Aging, Cell Senescence, and Chronic Disease: Emerging Therapeutic Strategies.

PMID- 30242335
TI  - Relationship of Interleukin-1beta Blockade With Incident Gout and Serum Uric Acid
      Levels: Exploratory Analysis of a Randomized Controlled Trial.
AB  - Background: Although studies have shown that interleukin-1beta (IL-1beta)
      inhibitors can shorten gout attacks, whether they can prevent gout attacks is
      unclear. Objective: To examine the relationship among canakinumab, a monoclonal
      antibody targeting IL-1beta; serum uric acid levels; and the incidence of gout
      attacks. Design: Secondary exploratory analysis of a randomized controlled trial.
      (ClinicalTrials.gov: NCT01327846). Setting: Many clinical sites in 39 countries.
      Participants: 10 059 patients with a prior myocardial infarction and a high
      sensitivity C-reactive protein (hsCRP) level of at least 19.1 nmol/L.
      Intervention: Random allocation to canakinumab (50 mg, 150 mg, or 300 mg) versus
      placebo, administered subcutaneously every 3 months. Measurements: Rates of gout
      attacks were compared across patients with different baseline concentrations of
      serum uric acid (<=404.5 umol/L, 404.6 to 535.3 umol/L, and >=535.4 umol/L) and
      in different intervention groups in Cox proportional hazards regression models.
      Results: The median baseline concentration of serum uric acid was 362.9 umol/L
      (interquartile range, 309.3 to 428.3 umol/L), and median follow-up was 3.7 years.
      Among participants receiving placebo, incidence rates of gout attacks for serum
      uric acid concentrations of 404.5 umol/L or lower, 404.6 to 535.3 umol/L, and
      535.4 umol/L or higher were 0.28, 1.36, and 5.94, respectively, per 100 person
      years. Canakinumab did not affect serum uric acid levels over time yet
      significantly reduced rates of gout attacks at all baseline concentrations of
      serum uric acid: Hazard ratios were 0.40 (95% CI, 0.22 to 0.73) for
      concentrations of 404.5 umol/L or lower, 0.48 (CI, 0.31 to 0.74) for those
      between 404.6 and 535.3 umol/L, and 0.45 (CI, 0.28 to 0.72) for those of 535.4
      umol/L or higher. Limitation: No adjudication of gout attacks. Conclusion:
      Quarterly canakinumab administration was associated with significantly reduced
      risk for gout attacks without any change in serum uric acid levels. These data
      have relevance for the development of agents for gout that target the IL-1beta
      pathway of innate immunity. Primary Funding Source: Novartis.

PMID- 30242337
TI  - Aging as a Biological Target for Prevention and Therapy.

PMID- 30242338
TI  - Association of Fludeoxyglucose F 18-Labeled Positron Emission Tomography and
      Computed Tomography With the Detection of Oropharyngeal Cancer Recurrence.
AB  - Importance: No guidelines at present describe when fludeoxyglucose F 18-labeled
      positron emission tomography and computed tomography (FDG PET-CT) should be used
      in the initial posttreatment period for evaluation of oropharyngeal squamous cell
      carcinoma treatment outcome and recurrence. Objective: To compare accuracies of
      the initial posttreatment PET-CT between primary treatment groups and to define
      indicators of false-positive findings. Design, Setting, and Participants: This
      retrospective cohort study identified adults with a new diagnosis of
      oropharyngeal squamous cell carcinoma who received treatment with curative intent
      from October 1, 2006, through November 30, 2016, using the Alberta Cancer
      Registry (n = 380). Patients who underwent PET-CT within 1 year of treatment
      completion were included (n = 190). Of these, 103 patients (54.2%) had PET-CT
      findings positive for residual or recurrent disease, and 61 (32.1%) had false
      positive findings. Among the 61 patients, 42 (68.9%) had received
      chemoradiotherapy (CRT) and 19 (31.1%) had primary surgery. Forty-two patients
      had true-positive findings, indicating a prevalence rate of disease of 22.1%.
      Data were analyzed from July through October 2017. Exposures: One of 2 primary
      treatment modalities (surgery with or without adjuvant therapy vs CRT). All
      patients had posttreatment FDG PET-CT. Main Outcomes and Measures: Primary
      outcome measures included the diagnostic odds ratio, sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) of PET-CT
      for detecting residual and/or recurrent disease. A multivariate analysis
      determined indicators of false-positive findings. Discriminative ability was
      assessed using receiver operating characteristic curve analysis of maximum
      standardized uptake value (SUVmax) metabolic data. Results: Of the 190
      participants, 77.9% were men, with a mean (SD) age at diagnosis of 58.5 (8.5)
      years. The diagnostic odds ratio was 19.3 (95% CI, 5.7-65.1); pooled sensitivity,
      93.3% (95% CI, 80.7%-98.3%); and pooled specificity, 57.9% (95% CI, 49.4%-66.0%).
      The PPV of detecting disease was 54.7% (95% CI, 38.8%-69.8%) for primary surgery
      and 31.1% (95% CI, 20.2%-44.4%) for CRT. The NPV was 100% (95% CI, 94.7%-100%)
      for primary surgery and 96.6% (95% CI, 89.5%-99.1%) for CRT. Multivariate
      analysis identified treatment type, p16 disease, and smoking status as indicative
      of false-positive findings. In the receiver operating characteristic curve
      analysis for primary tumors, the optimal cutoff SUVmax for indicating true- vs
      false-positive results was 5.1 for surgically treated patients (area under the
      curve, 0.729; 95% CI, 0.570-0.888) and 5.3 for patients treated with CRT (area
      under the curve, 0.844; 95% CI, 0.700-0.989). Conclusions and Relevance: The
      results indicate a higher specificity for FDG PET-CT for initial posttreatment
      surveillance imaging among patients treated with primary surgery compared with
      nonsurgical management. Both sets of patients with posttreatment FDG PET-CT
      findings with an SUVmax greater than 5.0 should undergo close evaluation for
      possible residual or recurrent disease.

PMID- 30242340
TI  - Concussion Evaluation and Management: An Osteopathic Perspective.
AB  - Concussions have been increasingly reported over the past decade, but the
      reported incidence likely minimizes the actual numbers of people affected.
      Associated symptoms include emotional, somatic, and cognitive complaints, which
      may be prolonged in patients with certain risk factors. Neurologic examination is
      necessary to exclude upper motor neuron lesions and thus the need for brain
      imaging. Cervical conditions are often found concurrently with head injury and
      displays a similar presentation to concussions. Therefore, determining symptom
      origin can be problematic. Neuropsychological, oculomotor, and balance
      evaluations expose specific deficits that can be successfully managed with
      rehabilitation. Osteopathic assessment of the cranium, spine, sacrum, and thorax
      for somatic dysfunctions allows for prudent interventions. Patients involved in
      sports may begin an established graduated return-to-play protocol once cleared by
      their physician. Concurrently, a parallel return-to-learn program, with
      applicable academic accommodations, is recommended.

PMID- 30242342
TI  - Accuracy of Smartphone Self-Hearing Test Applications Across Frequencies and
      Earphone Styles in Adults.
AB  - Purpose: The purpose of this study is to evaluate smartphone-based self-hearing
      test applications (apps) for accuracy in threshold assessment and validity in
      screening for hearing loss across frequencies and earphone transducer styles.
      Method: Twenty-two adult participants (10 = normal hearing; 12 = sensorineural
      hearing loss; n = 44 ears) underwent conventional audiometry and performed 6 self
      administered hearing tests using two iPhone-based apps (App 1 = uHear [Version
      2.0.2, Unitron]; App 2 = uHearingTest [Version 1.0.3, WooFu Tech, LLC.]) each
      with 3 different transducers (earbud earphones, supra-aural headphones,
      circumaural headphones). Hearing sensitivity results using the smartphone apps
      across frequencies and transducers were compared with conventional audiometry.
      Results: Differences in accuracy were revealed between the hearing test apps
      across frequencies and earphone styles. The uHear app using the iPhone standard
      EarPod earbud earphones was accurate to conventional thresholds (p > .002 with
      Bonferroni correction) at 1000, 2000, 4000, and 6000 Hz and found valid (81%-100%
      sensitivity, specificity, positive and negative predictive values) for screening
      mild or greater hearing loss (> 25 dB HL) at 500, 1000, 2000, 4000, and 6000 Hz.
      The uHearingTest app was accurate in threshold assessment and determined valid
      for screening mild or greater hearing loss (> 25 dB HL) using supra-aural
      headphones at 2000, 4000, and 8000 Hz. Conclusions: Self-hearing test apps can be
      accurate in hearing threshold assessment and screening for mild or greater
      hearing loss (> 25 dB HL) when using appropriate transducers. To ensure accuracy,
      manufacturers should specify earphone model instructions to users of smartphone
      based self-hearing test apps.

PMID- 30242343
TI  - Erratum.

PMID- 30242341
TI  - Stealing Cookies in the Twenty-First Century: Measures of Spoken Narrative in
      Healthy Versus Speakers With Aphasia.
AB  - Purpose: Our goal was to evaluate an updated version of the "Cookie Theft"
      picture by obtaining norms based on picture descriptions by healthy controls for
      total content units (CUs), syllables per CU, and the ratio of left-right CUs. In
      addition, we aimed to compare these measures from healthy controls to picture
      descriptions obtained from individuals with poststroke aphasia and primary
      progressive aphasia (PPA) to assess whether these measures can capture
      impairments in content and efficiency of communication. Method: Using an updated
      version of this picture, we analyzed descriptions from 50 healthy controls to
      develop norms for numbers of syllables, total CUs, syllables per CU, and left
      right CU. We provide preliminary data from 44 individuals with aphasia (19 with
      poststroke aphasia and 25 with PPA). Results: A total of 96 CUs were established
      based on the written transcriptions of spoken picture descriptions of the 50
      control participants. There was a significant effect of group on total CUs,
      syllables, syllables per CU, and left-right CUs. The poststroke participants
      produced significantly fewer total CU and syllables than those with PPA. Each
      aphasic group produced significantly fewer total CUs, fewer syllables, more
      syllables per CU, and lower left-right CUs (indicating a right-sided bias)
      compared to controls. Conclusions: Results show that the measures of numbers of
      syllables, total CUs, syllables per CU, and left-right CUs can distinguish
      language output of individuals with aphasia from controls and capture impairments
      in content and efficiency of communication. A limitation of this study is that we
      evaluated only 44 individuals with aphasia. In the future, we will evaluate other
      measures, such as CUs per minute, lexical variability, grammaticality, and ratio
      of nouns to verbs. Supplemental Material: https://doi.org/10.23641/asha.7015223.

PMID- 30242344
TI  - Development of Phonological, Lexical, and Syntactic Abilities in Children With
      Cochlear Implants Across the Elementary Grades.
AB  - Purpose: This study assessed phonological, lexical, and morphosyntactic abilities
      at 6th grade for a group of children previously tested at 2nd grade to address 4
      questions: (a) Do children with cochlear implants (CIs) demonstrate deficits at
      6th grade? (b) Are those deficits greater, the same, or lesser in magnitude than
      those observed at 2nd grade? (c) How do the measured skills relate to each other?
      and (d) How do treatment variables affect outcome measures? Participants: Sixty
      two 6th graders (29 with normal hearing, 33 with CIs) participated, all of whom
      had their language assessed at 2nd grade. Method: Data are reported for 12
      measures obtained at 6th grade, assessing phonological, lexical, and
      morphosyntactic abilities. Between-groups analyses were conducted on 6th-grade
      measures and the magnitude of observed effects compared with those observed at
      2nd grade. Correlational analyses were performed among the measures at 6th grade.
      Cross-lagged analyses were performed on specific 2nd- and 6th-grade measures of
      phonological awareness, vocabulary, and literacy to assess factors promoting
      phonological and lexical development. Treatment effects of age of 1st CI,
      preimplant thresholds, and bimodal experience were evaluated. Results: Deficits
      remained fairly consistent in type and magnitude across elementary school. The
      largest deficits were found for phonological skills and the least for
      morphosyntactic skills, with lexical skills intermediate. Phonological and
      morphosyntactic skills were largely independent of each other; lexical skills
      were moderately related to phonological skills but not morphosyntactic skills.
      Literacy acquisition strongly promoted both phonological and lexical development.
      Of the treatment variables, only bimodal experience affected outcomes and did so
      positively. Conclusions: Congenital hearing loss puts children at continued risk
      of language deficits, especially for phonologically based skills. Two
      interventions that appear to ameliorate that risk are providing a period of
      bimodal stimulation and strong literacy instruction.

PMID- 30242345
TI  - Accuracy of the Pediatric End-stage Liver Disease Score in Estimating
      Pretransplant Mortality Among Pediatric Liver Transplant Candidates.
AB  - Importance: Fair allocation of livers between pediatric and adult recipients is
      critically dependent on the accuracy of mortality estimates afforded by the
      Pediatric End-stage Liver Disease (PELD) and Model for End-stage Liver Disease,
      respectively. Widespread reliance on exceptions for pediatric recipients suggests
      that the 2 systems may not be comparable. Objective: To evaluate the accuracy of
      the PELD score in estimating 90-day pretransplant mortality among pediatric
      patients on the United Network for Organ Sharing (UNOS) waiting list. Design,
      Setting, and Participants: Patients who were listed from February 27, 2002, to
      March 31, 2014, for primary liver transplant were included in this retrospective
      analysis and were followed up for at least 2 years through June 17, 2016. The
      study analyzed 2 cohorts using the UNOS Standard Transplant Analysis and Research
      data files. The full cohort comprised 4298 patients (<18 years of age) who had
      chronic liver disease (excluding cancer). The reduced cohort (n = 2421) excluded
      patients receiving living donor transplantation or PELD exception points. Main
      Outcomes and Measures: Observed and expected 90-day pretransplant mortality rates
      evaluated at 10-point interval PELD levels. Results: Among the 4298 patients in
      the full cohort (mean [SD] age, 2.5 [4.2] years; 2251 [52.4%] female; 2201
      [51.2%] white), PELD scores and mortality were concordant (C statistic, 0.8387
      [95% CI, 0.8191-0.8584] for the full cohort and 0.8123 [95% CI, 0.7919-0.8327]
      for the reduced cohort). However, the estimated 90-day mortality using the PELD
      score underestimated the actual probability of death by as much as 17%.
      Conclusions and Relevance: With use of the PELD score, the ranking of risk among
      children was preserved, but direct comparisons between adult and pediatric
      candidates were not accurate. Children with chronic liver disease who are in need
      of transplant may be at a disadvantage compared with adults in a similar
      situation.

PMID- 30242346
TI  - Assessment of the Effect of Adjustment for Patient Characteristics on Hospital
      Readmission Rates: Implications for Pay for Performance.
AB  - Importance: In several pay-for-performance programs, Medicare ties payments to
      readmission rates but accounts only for a limited set of patient characteristics
      and no measures of social risk-when assessing performance of health care
      providers (clinicians, practices, hospitals, or other organizations). Debate
      continues over whether accounting for social risk would mitigate inappropriate
      penalties or would establish lower standards of care for disadvantaged patients
      if they are served by lower-quality providers. Objectives: To assess changes in
      hospital performance on readmission rates after adjusting for additional clinical
      and social patient characteristics by using methods that distinguish the
      association between patient characteristics and readmission from between-hospital
      differences in quality. Design, Setting, and Participants: Using Medicare claims
      for admissions in 2013 through 2014 and linked US Census data, we assessed
      several clinical and social characteristics of patients that are not currently
      used for risk adjustment in the Hospital Readmission Reduction Program. We
      compared hospital readmission rates with and without adjustment for these
      additional characteristics, using only the average within-hospital associations
      between patient characteristics and readmission as the basis for adjustment,
      thereby appropriately excluding hospitals' distinct contributions to readmission
      from the adjustment. Main Outcomes and Measures: All-cause readmission within 30
      days of discharge. Results: The study sample consisted of 1 169 014 index
      admissions among 1 003 664 unique Medicare beneficiaries (41.5% men; mean [SD]
      age, 79.9 [8.3] years) in 2215 hospitals. Compared with adjustment for patient
      characteristics currently implemented by Medicare, adjustment for the additional
      characteristics reduced overall variation in hospital readmission rates by 9.6%,
      changed rates upward or downward by 0.37 to 0.72 percentage points for the 10% of
      hospitals most affected by the additional adjustments (+/-30.3% to +/-58.9% of
      the hospital-level standard deviation), and would be expected to reduce penalties
      (in relative terms) by 52%, 46%, and 41% for hospitals with the largest 1%, 5%,
      and 10% of penalty reductions, respectively. The additional adjustments reduced
      the mean difference in readmission rates between hospitals in the top and bottom
      quintiles of high-risk patients by 0.53 percentage points (95% CI, 0.50-0.55; P <
      .001), or 54% of the difference estimated with CMS adjustments alone. Both
      clinical and social characteristics contributed to these reductions, and these
      reductions were considerably greater for conditions targeted by the Hospital
      Readmission Reduction Program. Adjustment for social characteristics resulted in
      greater changes in rates of readmission or death than in rates of readmission
      alone. Conclusions and Relevance: Hospitals serving higher-risk patients may be
      penalized substantially because of the patients they serve rather than their
      quality of care. Adjusting solely for within-hospital associations may allow
      adjustment for additional patient characteristics to mitigate unintended
      consequences of pay for performance without holding hospitals to different
      standards because of the patients they serve.

PMID- 30242347
TI  - Rapid Vision Loss in a Young Woman.

PMID- 30242348
TI  - Prevalence of Adverse Childhood Experiences From the 2011-2014 Behavioral Risk
      Factor Surveillance System in 23 States.
AB  - Importance: Early adversity is associated with leading causes of adult morbidity
      and mortality and effects on life opportunities. Objective: To provide an updated
      prevalence estimate of adverse childhood experiences (ACEs) in the United States
      using a large, diverse, and representative sample of adults in 23 states. Design,
      Setting, and Participants: Data were collected through the Behavioral Risk Factor
      Surveillance System (BRFSS), an annual, nationally representative telephone
      survey on health-related behaviors, health conditions, and use of preventive
      services, from January 1, 2011, through December 31, 2014. Twenty-three states
      included the ACE assessment in their BRFSS. Respondents included 248 934
      noninstitutionalized adults older than 18 years. Data were analyzed from March 15
      to April 25, 2017. Main Outcomes and Measures: The ACE module consists of 11
      questions collapsed into the following 8 categories: physical abuse, emotional
      abuse, sexual abuse, household mental illness, household substance use, household
      domestic violence, incarcerated household member, and parental separation or
      divorce. Lifetime ACE prevalence estimates within each subdomain were calculated
      (range, 1.00-8.00, with higher scores indicating greater exposure) and stratified
      by sex, age group, race/ethnicity, annual household income, educational
      attainment, employment status, sexual orientation, and geographic region.
      Results: Of the 214 157 respondents included in the sample (51.51% female),
      61.55% had at least 1 and 24.64% reported 3 or more ACEs. Significantly higher
      ACE exposures were reported by participants who identified as black (mean score,
      1.69; 95% CI, 1.62-1.76), Hispanic (mean score, 1.80; 95% CI, 1.70-1.91), or
      multiracial (mean score, 2.52; 95% CI, 2.36-2.67), those with less than a high
      school education (mean score, 1.97; 95% CI, 1.88-2.05), those with income of less
      than $15 000 per year (mean score, 2.16; 95% CI, 2.09-2.23), those who were
      unemployed (mean score, 2.30; 95% CI, 2.21-2.38) or unable to work (mean score,
      2.33; 95% CI, 2.25-2.42), and those identifying as gay/lesbian (mean score 2.19;
      95% CI, 1.95-2.43) or bisexual (mean score, 3.14; 95% CI, 2.82-3.46) compared
      with those identifying as white, those completing high school or more education,
      those in all other income brackets, those who were employed, and those
      identifying as straight, respectively. Emotional abuse was the most prevalent ACE
      (34.42%; 95% CI, 33.81%-35.03%), followed by parental separation or divorce
      (27.63%; 95% CI, 27.02%-28.24%) and household substance abuse (27.56%; 95% CI,
      27.00%-28.14%). Conclusions and Relevance: This report demonstrates the burden of
      ACEs among the US adult population using the largest and most diverse sample to
      date. These findings highlight that childhood adversity is common across
      sociodemographic characteristics, but some individuals are at higher risk of
      experiencing ACEs than others. Although identifying and treating ACE exposure is
      important, prioritizing primary prevention of ACEs is critical to improve health
      and life outcomes throughout the lifespan and across generations.

PMID- 30242349
TI  - Use of Deep Learning for Detailed Severity Characterization and Estimation of 5
      Year Risk Among Patients With Age-Related Macular Degeneration.
AB  - Importance: Although deep learning (DL) can identify the intermediate or advanced
      stages of age-related macular degeneration (AMD) as a binary yes or no,
      stratified gradings using the more granular Age-Related Eye Disease Study (AREDS)
      9-step detailed severity scale for AMD provide more precise estimation of 5-year
      progression to advanced stages. The AREDS 9-step detailed scale's complexity and
      implementation solely with highly trained fundus photograph graders potentially
      hampered its clinical use, warranting development and use of an alternate AREDS
      simple scale, which although valuable, has less predictive ability. Objective: To
      describe DL techniques for the AREDS 9-step detailed severity scale for AMD to
      estimate 5-year risk probability with reasonable accuracy. Design, Setting, and
      Participants: This study used data collected from November 13, 1992, to November
      30, 2005, from 4613 study participants of the AREDS data set to develop deep
      convolutional neural networks that were trained to provide detailed automated AMD
      grading on several AMD severity classification scales, using a multiclass
      classification setting. Two AMD severity classification problems using criteria
      based on 4-step (AMD-1, AMD-2, AMD-3, and AMD-4 from classifications developed
      for AREDS eligibility criteria) and 9-step (from AREDS detailed severity scale)
      AMD severity scales were investigated. The performance of these algorithms was
      compared with a contemporary human grader and against a criterion standard
      (fundus photograph reading center graders) used at the time of AREDS enrollment
      and follow-up. Three methods for estimating 5-year risk were developed, including
      one based on DL regression. Data were analyzed from December 1, 2017, through
      April 15, 2018. Main Outcomes and Measures: Weighted kappa scores and mean
      unsigned errors for estimating 5-year risk probability of progression to advanced
      AMD. Results: This study used 67 401 color fundus images from the 4613 study
      participants. The weighted kappa scores were 0.77 for the 4-step and 0.74 for the
      9-step AMD severity scales. The overall mean estimation error for the 5-year risk
      ranged from 3.5% to 5.3%. Conclusions and Relevance: These findings suggest that
      DL AMD grading has, for the 4-step classification evaluation, performance
      comparable with that of humans and achieves promising results for providing AMD
      detailed severity grading (9-step classification), which normally requires highly
      trained graders, and for estimating 5-year risk of progression to advanced AMD.
      Use of DL has the potential to assist physicians in longitudinal care for
      individualized, detailed risk assessment as well as clinical studies of disease
      progression during treatment or as public screening or monitoring worldwide.

PMID- 30242350
TI  - Antibiotics for Sepsis-Finding the Equilibrium.

PMID- 30242351
TI  - Is the Association of Retinal Venous Malformations With Venous Malformations of
      the Brain Clinically Meaningful?-Reply.

PMID- 30242352
TI  - Progress in Automated Deep Learning for Macular Degeneration.

PMID- 30242353
TI  - Trends in Hospital Admissions for Nonfatal Adversity-Related Injury Among Youths
      in England, 2002-2016.

PMID- 30242354
TI  - Is the Pediatric End-stage Liver Disease Score Truly a Detriment to Pediatric
      Liver Allocation?

PMID- 30242355
TI  - Effectiveness of Audiologist-Delivered Cognitive Behavioral Therapy for Tinnitus
      and Hyperacusis Rehabilitation: Outcomes for Patients Treated in Routine
      Practice.
AB  - Objective: The aim was to assess the effectiveness of cognitive behavioral
      therapy (CBT) for tinnitus and/or hyperacusis delivered by audiologists working
      in the National Health Service in the United Kingdom. Design: This was a
      retrospective study, based on questionnaires assessing tinnitus and hyperacusis
      and insomnia before and after CBT. Study Sample: Data were gathered for 68
      consecutive patients (average age = 52.5 years) who enrolled for CBT. Results:
      All measures showed significant improvements after CBT. Effect sizes for patients
      who completed CBT were 1.13 for Tinnitus Handicap Inventory scores; 0.76 for
      Hyperacusis Questionnaire scores; 0.71, 0.95, and 0.93 for tinnitus loudness,
      annoyance, and effect on life, respectively, measured using the Visual Analog
      Scale; and 0.94 for the Insomnia Severity Index score. An analysis including
      those who dropped out also showed significant improvements for all measures.
      Conclusion: Audiologist-delivered CBT led to significant improvements in self
      report measures of tinnitus and hyperacusis handicap and insomnia. The methods
      described here may be used when designing future randomized controlled trials of
      efficacy.

PMID- 30242356
TI  - Dichoptic Attentive Motion Tracking is Biased Toward the Nonamblyopic Eye in
      Strabismic Amblyopia.
AB  - Purpose: To determine whether attention is biased toward the nonamblyopic eye
      under binocular viewing conditions in adults with anisometropic or strabismic
      amblyopia. We first determined whether attention could be allocated
      preferentially to one eye in visually normal observers performing a dichoptic
      attentive motion tracking task. We then assessed dichoptic attentive motion
      tracking in amblyopia. Methods: Participants performed a multiple-object tracking
      task under the following three viewing conditions: target dots to the dominant
      eye and distractor dots to the nondominant eye (DE condition), vice versa (NDE
      condition), or all dots to both eyes (binocular condition). Interocular
      attentional asymmetry scores were computed as the difference in accuracy between
      DE and NDE conditions. An interocular contrast difference favoring the amblyopic
      eye was used for all conditions to neutralize amblyopic eye suppression. To test
      for confounding effects of suppression, participants completed a separate dot
      enumeration task under dichoptic presentation conditions to obtain an interocular
      enumeration asymmetry score. Results: Participants with normal vision
      demonstrated similar accuracy between the DE and NDE conditions and exhibited
      slightly impaired performance under dichoptic compared with binocular viewing
      conditions. Participants with strabismic/mixed amblyopia had significantly higher
      interocular attentional asymmetry than participants with normal vision or with
      anisometropic amblyopia, whereby attention was biased toward the nonamblyopic
      eye. The latter two groups did not exhibit a bias in interocular attention. No
      interocular asymmetries for the enumeration task were observed for any group.
      Conclusions: A nonamblyopic eye bias in the interocular allocation of attention
      may contribute to the binocular vision impairments caused by strabismic
      amblyopia.

PMID- 30242357
TI  - In Vitro Amoebicidal Activity of Titanium Dioxide/UV-A Combination Against
      Acanthamoeba.
AB  - Purpose: To assess the amoebicidal effect of titanium dioxide (TiO2)/UV-A
      combination against Acanthamoeba sp trophozoites and cysts. Methods: The
      amoebicidal effect of the TiO2/UV-A combination was tested on trophozoites and
      cysts of clinical isolates of Acanthamoeba hatchetti and Acanthamoeba sp genotype
      T4, obtained from two severe cases of ulcerative keratitis. Samples of cultured
      Acanthamoeba were transferred to a 96-well plate. We tested the effect of sterile
      water (blank control), TiO2 alone, UV-A alone, TiO2 and additional UV-A exposure,
      chlorhexidine 0.02% alone, chlorhexidine 0.02% and TiO2, chlorhexidine and UV-A,
      chlorhexidine 0.02% and TiO2, and additional UV-A exposure. Cell viability
      assessment was done using the trypan blue dye exclusion method. Results: The
      combination of TiO2 with UV-A demonstrated antitrophozoite and anticyst activity
      (P < 0.05). This in vitro study showed a synergistic effect of the association of
      chlorhexidine with TiO2 and UV-A on cysts (P < 0.001). Conclusions: Given the in
      vitro synergistic effectiveness of the association of chlorhexidine with TiO2 and
      UV-A against cysts, the treatment of Acanthamoeba keratitis could be improved by
      this new therapeutic approach.

PMID- 30242358
TI  - IFT52 as a Novel Candidate for Ciliopathies Involving Retinal Degeneration.
AB  - Purpose: Mutations in the intraflagellar transport protein 52 homolog (IFT52)
      gene are reported to interrupt ciliary function and cause short-rib thoracic
      dysplasia (SRTD), a specific form of skeletal ciliopathy. However, the roles of
      these mutations in retinal ciliopathy are inexplicit. We herein aim to study the
      impact of IFT52 mutations in retinopathies. Methods: A patient with syndromic
      ciliopathy, presenting mild SRTD (skeletal ciliopathy) and Liber congenital
      amaurosis (LCA; retinal ciliopathy), and nine unaffected family members were
      recruited. Comprehensive systemic evaluations, including ophthalmic tests, were
      received by the patient. Whole genome sequencing (WGS) was applied for genetic
      annotation. An in vitro cell system was employed to study the pathogenicity of
      the variant. Results: WGS identified a homozygous missense variation in IFT52,
      c.556A>G (p.T186A), carried by the patient but absent in both unaffected
      siblings. In silico analysis supported the pathogenic nature of this highly
      conserved variant. Structural analysis suggested that this substitution could
      generate a novel hydrogen bond between the mutated residue 186 and proline at
      residue 192, thus potentially interrupting the tertiary structure and the
      stability of the IFT52 protein. In vitro cellular study indicated that this
      mutation might disturb the stability of encoded IFT52 protein and dramatically
      disrupt cilia elongation in hTERT-RPE1 cells in a loss-of-function manner.
      Conclusions: This report expands ocular phenotypes of IFT52 mutation-caused
      ciliopathy to include retinal ciliopathy and demonstrates its deleterious nature
      in interrupting primary ciliary function. Our study hence highlights the need for
      screening for IFT52 mutations in LCA patients and ophthalmic reviews of patients
      carrying IFT52 mutations.

PMID- 30242359
TI  - Predicting Visual Acuity From Visual Field Sensitivity in Age-Related Macular
      Degeneration.
AB  - Purpose: To investigate how well visual field sensitivity predicts visual acuity
      at the same locations in macular disease, and to assess whether such predictions
      may be useful for selecting an optimum area for fixation training. Methods:
      Visual field sensitivity and acuity were measured at nine locations in the
      central 10 degrees  in 20 people with AMD and stable foveal fixation. A linear
      mixed model was constructed to predict acuity from sensitivity, taking into
      account within-subject effects and eccentricity. Cross validation was used to
      test the ability to predict acuity from sensitivity in a new patient. Simulations
      tested whether sensitivity can predict nonfoveal regions with greatest acuity in
      individual patients. Results: Visual field sensitivity (P < 0.0001), eccentricity
      (P = 0.007), and random effects of subject on eccentricity (P = 0.043) improved
      the model. For known subjects, 95% of acuity prediction errors (predicted -
      measured acuity) fell within -0.21 logMAR to +0.18 logMAR (median +0.00 logMAR).
      For unknown subjects, cross validation gave 95% of acuity prediction errors
      within -0.35 logMAR to +0.31 logMAR (median -0.01 logMAR). In simulations, the
      nonfoveal location with greatest predicted acuity had greatest "true" acuity on
      median 26% of occasions, and median difference in acuity between the location
      with greatest predicted acuity and the best possible location was +0.14 logMAR
      (range +0.04 to +0.17). Conclusions: The relationship between sensitivity and
      acuity in macular disease is not strongly predictive. The location with greatest
      sensitivity on microperimetry is unlikely to represent the location with the best
      visual acuity, even if eccentricity is taken into account.

PMID- 30242360
TI  - Mitochondrial DNA Variation and Disease Susceptibility in Primary Open-Angle
      Glaucoma.
AB  - Purpose: To determine whether mitochondrial DNA haplogroups or rare variants
      associate with primary open-angle glaucoma in subjects of European descent.
      Methods: A case-control comparison of age- and sex-matched cohorts of 90 primary
      open-angle glaucoma patients and 95 population controls. Full mitochondrial DNA
      sequences from peripheral blood were generated by next-generation sequencing and
      compared to the revised Cambridge Reference Sequence to define mitochondrial
      haplogroups and variants. Results: Most subjects were of the major European
      haplogroups H, J, K, U, and T. Logistic regression analysis showed haplogroup U
      to be significantly underrepresented in male primary open-angle glaucoma subjects
      (odds ratio 0.25; 95% confidence interval [CI] 0.09-0.67; P = 0.007; Bonferroni
      multiple testing P = 0.022). Variants in the mitochondrial DNA gene MT-ND2 were
      overrepresented in the control group (P = 0.005; Bonferroni multiple testing
      correction P = 0.015). Conclusions: Mitochondrial DNA ancestral lineages modulate
      the risk for primary open-angle glaucoma in populations of European descent.
      Haplogroup U and rare variants in the mitochondrial DNA-encoded MT-ND2 gene may
      be protective against primary open-angle glaucoma. Larger studies are warranted
      to explore haplogroup associations with disease risk in different ethnic groups
      and define biomarkers of primary open-angle glaucoma endophenotypes to target
      therapeutic strategies.

PMID- 30242361
TI  - Prevalence, Risk Factors, and Impact of Myopic Macular Degeneration on Visual
      Impairment and Functioning Among Adults in Singapore.
AB  - Purpose: To determine the prevalence, risk factors, and impact of myopic macular
      degeneration (MMD) on visual impairment and functioning among adults in
      Singapore. Methods: A comprehensive eye examination, including subjective
      refraction, axial length, and visual acuity (VA) measurements, was performed in
      adults aged >=40 years in the Singapore Epidemiology of Eye Diseases (SEED)
      study. From fundus photographs, MMD was graded using the International META-PM
      classification. Vision-specific functioning (VSF) was assessed with a validated
      visual-functioning questionnaire (VF-11) using Rasch analysis. Results: A total
      of 8716 phakic subjects were included in this analysis. The mean age (+/- SD) was
      57.2 +/- 9.5 years (33.5% Malays, 33.2% Indians, and 33.3% Chinese). The
      prevalence of myopia (spherical equivalent [SE] <= -0.5 diopters [D]) and high
      myopia (SE <= -5.0 D) was 35.7% and 6.0%, respectively. The age-standardized
      prevalence of MMD was 3.8% (95% confidence interval [CI], 3.4-4.3%). The
      prevalence of MMD was 7.7% among low to moderate myopes, and 28.7% among high
      myopes. The prevalence of MMD increased nonlinearly with SE and age. MMD was
      associated with older age, more myopic SE, and lower education. Subjects with
      Meta-PM categories 3 or 4 in the better-seeing eye had worse best-corrected VA
      (beta, 0.19; 95%CI, 0.16-0.23) and poorer VSF (beta, -9.7; 95%CI, -17.6 to -1.8)
      than those without MMD after multivariate adjustments. Conclusions: Approximately
      1 in 26 phakic adults in Singapore has MMD. Older age and myopic SE are major
      risk factors of MMD. Severe MMD has a substantial impact on visual impairment and
      functioning.

PMID- 30242362
TI  - Microvascular Changes in Peripapillary and Optic Nerve Head Tissues After
      Trabeculectomy in Primary Open-Angle Glaucoma.
AB  - Purpose: To determine microvasculature changes in the deep optic nerve head (ONH)
      and peripapillary tissues after trabeculectomy, and to correlate these with
      changes in the lamina cribrosa (LC) curvature. Methods: Fifty-six eyes with
      primary open-angle glaucoma that underwent trabeculectomy were included. The
      optic nerve and peripapillary microvasculature were evaluated in en face images
      obtained using optical coherence tomography (OCT) angiography (OCTA) before and 3
      months after trabeculectomy. The OCTA-derived vessel density (VD) was calculated
      in each layer segmented into the prelaminar tissue (PLT), LC, peripapillary
      retina (PR), and peripapillary choroid (PPC). Swept-source OCT volume scanning of
      ONH was performed on the same day as OCTA to examine the change in LC curvature
      quantified as the LC curve index (LCCI). Results: At 3 months postoperative, the
      IOP and LCCI had significantly decreased (both P < 0.001). OCTA images revealed a
      significant increase in VD in the LC (P = 0.006), but not in the PLT, PR, or PPC.
      Twenty-six eyes showed both significant LCCI decrease and VD increase based on
      95% Bland-Altman limits of agreement. The VD increase in the LC was significantly
      associated with larger percentage reductions in IOP (P = 0.040) and LCCI (P <
      0.001) in the univariate analysis. Multivariate analysis revealed that only the
      LCCI reduction was a significant factor affecting the VD increase in the LC.
      Conclusions: A significant increase in VD was observed at the level of the LC
      after trabeculectomy. The VD increase was more strongly associated with the
      reduction in the LC curvature than with the reduction of IOP.

PMID- 30242364
TI  - Fractional Flow Reserve Measurement for the Physiological Assessment of Coronary
      Artery Stenosis Severity.

PMID- 30242365
TI  - Intelligent Use of the Fecal Immunochemical Test in Population-Based Screening.

PMID- 30242363
TI  - Sensitivity to S-Cone Stimuli and the Development of Myopia.
AB  - Purpose: Longitudinal chromatic aberration (LCA) is a color signal available to
      the emmetropization process that causes greater myopic defocus of short
      wavelengths than long wavelengths. We measured individual differences in
      chromatic sensitivity to explore the role LCA may play in the development of
      refractive error. Methods: Forty-four observers were tested psychophysically
      after passing color screening tests and a questionnaire for visual defects.
      Refraction was measured and only subjects with myopia or hyperopia without severe
      astigmatism participated. Psychophysical detection thresholds for 3 cyc/deg
      achromatic, L-, M-, and S-cone-isolating Gabor patches and low-frequency S-cone
      increment (S+) and decrement (S-) blobs were measured. Parametric Pearson
      correlations for refractive error versus threshold were calculated and
      nonparametric bootstrap 95% percentage confidence intervals (BCIs) for r were
      computed. Results: S-cone Gabor detection thresholds were higher than achromatic,
      L-, and M-cone Gabors. S-cone Gabor thresholds were higher than either S+ or S-
      blobs. These results are consistent with studies using smaller samples of
      practiced observers. None of the thresholds for the Gabor stimuli were correlated
      with refractive error (RE). A negative correlation with RE was observed for both
      S+ (r = -0.28; P = 0.06; BCI: r = -0.5, -0.04) and S- (r = -0.23; P = 0.13; BCI =
      -0.46, 0.01) blobs, although this relationship did not reach conventional
      statistical significance. Conclusions: Thresholds for S+ and S- stimuli were
      negatively related to RE, indicating that myopes may have reduced sensitivity to
      low spatial frequency S-cone stimuli. This reduced S-cone sensitivity might have
      played a role in their failure to emmetropize normally.

PMID- 30242366
TI  - Prevalence of Cannabis Use in Electronic Cigarettes Among US Youth.

PMID- 30242367
TI  - Bilateral Iris Metastasis From Pulmonary Adenocarcinoma.

PMID- 30242368
TI  - Treatment of Foveal Neovascularization in a Patient With Type 1 Diabetes.

PMID- 30242369
TI  - Mizuo-Nakamura Phenomenon in a Middle-aged Woman.

PMID- 30242370
TI  - A Surprise Guest-Insect Larva Under An Uncomplicated Laser-Assisted In Situ
      Keratomileusis Surgical Flap.

PMID- 30242373
TI  - Changes in Drug Pricing After Drug Shortages in the United States.

PMID- 30242376
TI  - Pediatric End-stage Liver Disease Scores as a Method of Assessing Mortality Risk
      or Prioritization to Transplantability: Let Us Save the Children.

PMID- 30242377
TI  - Deciding on the Best Multiple Sclerosis Therapy: Tough Choices.

PMID- 30242378
TI  - Much Choice, Much Confusion: Treating Basal Cell Carcinoma.

PMID- 30242379
TI  - Treatments of Primary Basal Cell Carcinoma of the Skin: A Systematic Review and
      Network Meta-analysis.
AB  - Background: Most interventions for basal cell carcinoma (BCC) have not been
      compared in head-to-head randomized trials. Purpose: To evaluate the comparative
      effectiveness and safety of treatments of primary BCC in adults. Data Sources:
      English-language searches of MEDLINE, Cochrane Central Register of Controlled
      Trials, Cochrane Database of Systematic Reviews, and Embase from inception to May
      2018; reference lists of guidelines and systematic reviews; and a search of
      ClinicalTrials.gov in August 2016. Study Selection: Comparative studies of
      treatments currently used in adults with primary BCC. Data Extraction: One
      investigator extracted data on recurrence, histologic clearance, clinical
      clearance, cosmetic outcomes, quality of life, and mortality, and a second
      reviewer verified extractions. Several investigators evaluated risk of bias for
      each study. Data Synthesis: Forty randomized trials and 5 nonrandomized studies
      compared 18 interventions in 9 categories. Relative intervention effects and mean
      outcome frequencies were estimated using frequentist network meta-analyses.
      Estimated recurrence rates were similar for excision (3.8% [95% CI, 1.5% to
      9.5%]), Mohs surgery (3.8% [CI, 0.7% to 18.2%]), curettage and diathermy (6.9%
      [CI, 0.9% to 36.6%]), and external-beam radiation (3.5% [CI, 0.7% to 16.8%]).
      Recurrence rates were higher for cryotherapy (22.3% [CI, 10.2% to 42.0%]),
      curettage and cryotherapy (19.9% [CI, 4.6% to 56.1%]), 5-fluorouracil (18.8% [CI,
      10.1% to 32.5%]), imiquimod (14.1% [CI, 5.4% to 32.4%]), and photodynamic therapy
      using methyl-aminolevulinic acid (18.8% [CI, 10.1% to 32.5%]) or aminolevulinic
      acid (16.6% [CI, 7.5% to 32.8%]). The proportion of patients reporting good or
      better cosmetic outcomes was better for photodynamic therapy using methyl
      aminolevulinic acid (93.8% [CI, 79.2% to 98.3%]) or aminolevulinic acid (95.8%
      [CI, 84.2% to 99.0%]) than for excision (77.8% [CI, 44.8% to 93.8%]) or
      cryotherapy (51.1% [CI, 15.8% to 85.4%]). Data on quality of life and mortality
      were too sparse for quantitative synthesis. Limitation: Data are sparse, and
      effect estimates are imprecise and informed by indirect comparisons. Conclusion:
      Surgical treatments and external-beam radiation have low recurrence rates for the
      treatment of low-risk BCC, but substantial uncertainty exists about their
      comparative effectiveness versus other treatments. Gaps remain regarding high
      risk BCC subtypes and important outcomes, including costs. Primary Funding
      Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42016043353).

PMID- 30242380
TI  - Association of Medical Scribes in Primary Care With Physician Workflow and
      Patient Experience.
AB  - Importance: Widespread adoption of electronic health records (EHRs) in medical
      care has resulted in increased physician documentation workload and decreased
      interaction with patients. Despite the increasing use of medical scribes for EHR
      documentation assistance, few methodologically rigorous studies have examined the
      use of medical scribes in primary care. Objective: To evaluate the association of
      use of medical scribes with primary care physician (PCP) workflow and patient
      experience. Design, Setting, and Participants: This 12-month crossover study with
      2 sequences and 4 periods was conducted from July 1, 2016, to June 30, 2017, in 2
      medical center facilities within an integrated health care system and included 18
      of 24 eligible PCPs. Interventions: The PCPs were randomly assigned to start the
      first 3-month period with or without scribes and then alternated exposure status
      every 3 months for 1 year, thereby serving as their own controls. The PCPs
      completed a 6-question survey at the end of each study period. Patients of
      participating PCPs were surveyed after scribed clinic visits. Main Outcomes and
      Measures: PCP-reported perceptions of documentation burden and visit
      interactions, objective measures of time spent on EHR activity and required for
      closing encounters, and patient-reported perceptions of visit quality. Results:
      Of the 18 participating PCPs, 10 were women, 12 were internal medicine
      physicians, and 6 were family practice physicians. The PCPs graduated from
      medical school a mean (SD) of 13.7 (6.5) years before the study start date.
      Compared with nonscribed periods, scribed periods were associated with less self
      reported after-hours EHR documentation (<1 hour daily during week: adjusted odds
      ratio [aOR], 18.0 [95% CI, 4.7-69.0]; <1 hour daily during weekend: aOR, 8.7; 95%
      CI, 2.7-28.7). Scribed periods were also associated with higher likelihood of PCP
      reported spending more than 75% of the visit interacting with the patient (aOR,
      295.0; 95% CI, 19.7 to >900) and less than 25% of the visit on a computer (aOR,
      31.5; 95% CI, 7.3-136.4). Encounter documentation was more likely to be completed
      by the end of the next business day during scribed periods (aOR, 2.8; 95% CI, 1.2
      7.1). A total of 450 of 735 patients (61.2%) reported that scribes had a positive
      bearing on their visits; only 2.4% reported a negative bearing. Conclusions and
      Relevance: Medical scribes were associated with decreased physician EHR
      documentation burden, improved work efficiency, and improved visit interactions.
      Our results support the use of medical scribes as one strategy for improving
      physician workflow and visit quality in primary care.

PMID- 30242381
TI  - Association Between Patient Cognitive and Functional Status and Medicare Total
      Annual Cost of Care: Implications for Value-Based Payment.
AB  - Importance: Medicare is moving toward value-based payment. The Merit-Based
      Incentive Payment System (MIPS) program judges outpatient clinicians' performance
      on a measure of annual Medicare spending. However, this measure may disadvantage
      outpatient clinicians who care for vulnerable populations because the algorithm
      omits meaningful determinants of cost. Objectives: To determine whether factors
      not included in Medicare risk adjustment, including patient neuropsychological
      and functional status, as well as local area health resources and economic
      conditions, are associated with Medicare total annual cost of care (TACC), and
      evaluate whether accounting for these factors is associated with improved TACC
      performance by outpatient safety-net clinicians. Design, Setting, and
      Participants: In this retrospective observational study, we used the Medicare
      Current Beneficiary Survey (MCBS) to examine patient-reported neuropsychological
      and functional status and the Area Health Resources File to obtain information on
      local area characteristics. Included were Medicare beneficiaries with annual
      physician or clinic visits to outpatient safety-net (federally qualified health
      centers and rural health clinics) and non-safety-net clinics, contributing 76 927
      person-years of data to the MCBS from 2006 through 2013. We used patient-level
      multivariable regression models to estimate the association between each factor
      and annual Medicare spending, and compared outpatient safety-net performance
      under current risk adjustment and after adding additional adjustment for these
      factors. Main Outcomes and Measures: Medicare TACC, measured as the total annual
      reimbursed amount per patient for Medicare Part A and Part B services, in all
      categories. Results: Our study included 111 414 unique identifiable physicians,
      and the final weighted sample included 213 904 324 patient-years (unweighted, 76
      927 patient-years) from 30 058 unique patients, of whom 17 478 (58.1%) were
      women. The mean (SD) patient age was 71.84 (12.48) years. The mean TACC was
      $9117. Those with higher than mean TACC included beneficiaries with depression
      ($14 436), dementia ($18 311), and difficulty with 3 or more activities of daily
      living (ADLs, $19 113) or instrumental ADLs ($17 443). After adjusting for
      comorbidities, depression and dementia were still associated with $2740 (95% CI,
      $2200-$2739) and $2922 (95% CI, $2399-$3445) higher TACC, respectively.
      Difficulty with 3 or more ADLs ($3121 higher; 95% CI, $2633-$3609) or
      instrumental ADLs ($895 higher; 95% CI, $452-$1337) was also associated with
      higher TACC. Adding these neuropsychological and functional factors, as well as
      local residence area factors, to risk adjustment calculations reduced outpatient
      safety-net clinicians' underperformance on Medicare TACC relative to non-safety
      net clinicians by 52% (from 0.098 to 0.047 difference in the observed to expected
      ratio). Conclusions and Relevance: Neuropsychological and functional impairment
      are common in Medicare beneficiaries and are associated with increased annual
      Medicare spending. Failure to account for these factors may inappropriately
      penalize outpatient clinicians who care for these vulnerable groups, such as
      safety-net clinicians, for factors that are arguably beyond their control.

PMID- 30242382
TI  - Errors in Potential Conflicts of Interest Disclosures, Author Affiliation, and
      Role of Funder.

PMID- 30242383
TI  - Treatment of Mucous Membrane Pemphigoid With Janus Kinase Inhibitor Baricitinib.

PMID- 30242384
TI  - From Lifespan to Healthspan.

PMID- 30242386
TI  - Steering bends and changing lanes: The impact of optic flow and road edges on two
      point steering control.
AB  - Successful driving involves steering corrections that respond to immediate
      positional errors while also anticipating upcoming changes to the road layout
      ahead. In popular steering models these tasks are often treated as separate
      functions using two points: the near region for correcting current errors, and
      the far region for anticipating future steering requirements. Whereas two-point
      control models can capture many aspects of driver behavior, the nature of
      perceptual inputs to these two "points" remains unclear. Inspired by experiments
      that solely focused on road-edge information (Land & Horwood, 1995), two-point
      models have tended to ignore the role of optic flow during steering control.
      There is recent evidence demonstrating that optic flow should be considered
      within two-point control steering models (Mole, Kountouriotis, Billington, &
      Wilkie, 2016). To examine the impact of optic flow and road edges on two-point
      steering control we used a driving simulator to selectively and systematically
      manipulate these components. We removed flow and/or road-edge information from
      near or far regions of the scene, and examined how behaviors changed when
      steering along roads where the utility of far-road information varied. While
      steering behaviors were strongly influenced by the road-edges, there were also
      clear contributions of optic flow to steering responses. The patterns of steering
      were not consistent with optic flow simply feeding into two-point control;
      rather, the global optic flow field appeared to support effective steering
      responses across the time-course of each trajectory.

PMID- 30242385
TI  - Serial dependence in numerosity perception.
AB  - Our conscious experience of the external world is remarkably stable and seamless,
      despite the intrinsically discontinuous and noisy nature of sensory information.
      Serial dependencies in visual perception-reflecting attractive biases making a
      current stimulus to appear more similar to previous ones-have been recently
      hypothesized to be involved in perceptual continuity. However, while these
      effects have been observed across a variety of visual features and at the neural
      level, several aspects of serial dependence and how it generalizes across visual
      dimensions is still unknown. Here we explore the behavioral signature of serial
      dependence in numerosity perception by assessing how the perceived numerosity of
      dot-array stimuli is biased by a task-irrelevant "inducer" stimulus presented
      before task-relevant stimuli. First, although prior work suggests that numerosity
      perception starts in the subcortex, the current study rules out a possible
      involvement of subcortical processing in serial dependence, confirming that the
      effect likely starts in the visual cortex. Second, we show that the effect is
      coarsely spatially localized to the position of the inducer stimulus. Third, we
      demonstrate that the effect is present even with a stimulus presentation
      procedure minimizing the involvement of post-perceptual processes, but only when
      participants actively pay attention to the inducer stimulus. Overall, these
      results provide a comprehensive characterization of serial dependencies in
      numerosity perception, demonstrating that attractive biases occur by means of
      spatially localized attentional modulations of early sensory activity.

PMID- 30242387
TI  - Saturation and brightness modulate the effect of depth on visual working memory.
AB  - Although previous studies show inconsistent results regarding the effect of depth
      perception on visual working memory (VWM), a recent finding shows that
      perceptually closer-in-depth items are better remembered than farther items when
      combining the congruent disparity and relative size cues. In this study, we
      employed a similar change detection paradigm to investigate the effects of
      saturation and brightness, alone or in combination with binocular disparity, on
      VWM. By varying the appearance of the memory items, we aimed to manipulate the
      visual salience as well as to simulate the aerial perspective cue that induces
      depth perception. We found that the change detection accuracy was significantly
      improved for brighter and more saturated items, but not for items solely with
      higher saturation. Additionally, combining saturation with the congruent
      disparity cue significantly improved memory performance for perceptually closer
      items over farther items. Conflicting the disparity cue with saturation
      eliminated the memory benefit for the closer items. These results indicate that
      saturation and brightness could modulate the effect of depth on VWM, and both
      visual salience and depth perception affect VWM possibly through a common
      underlying mechanism of setting priority for attentional selection.

PMID- 30242388
TI  - Extracting the orientation of rotating objects without object identification:
      Object orientation induction.
AB  - When a rotating object (inducer) is briefly replaced by a static face image (test
      stimulus), the orientation of the face appears to shift in the rotation direction
      of the inducer (object orientation induction, OOI). The OOI effect suggests that
      there is a process to continuously analyze and update the orientation of an
      object in motion. We investigated the perception of object orientation in motion,
      examining potential factors that contribute to OOI. Experiment 1 showed that the
      phenomenon is general to objects rather than specific to faces; OOI could be
      observed with non-face objects. Experiment 2 showed that OOI is a 3D effect, as
      the orientation shift for a bent-wire object depended on its configuration in the
      depth dimension. Experiment 3 showed that salient features are necessary to
      indicate the intrinsic orientation of the inducing object for producing OOI.
      Experiment 4 showed that change in the facing direction of the inducer object is
      a crucial factor for OOI, but neither the object shape nor its identity is
      important. A strong OOI effect was observed even when the inducer kept changing
      its shape and identity, as long as its direction change generated continuous
      rotation. Finally, Experiment 5 showed that OOI is a phenomenon in the pathway
      for fast visual processing. A single inducer presented shorter than 100ms before
      influenced the perceived orientation of the test stimulus. Together these results
      suggest that there is a predictive process that continuously analyzes and updates
      the orientation of rotating objects, independently of their identification.

PMID- 30242389
TI  - The Mandarin Version of the Consensus Auditory-Perceptual Evaluation of Voice
      (CAPE-V) and Its Reliability.
AB  - Purpose: The purpose of this study is to develop the Mandarin version of the
      Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) and evaluate its
      reliability compared with the Grade, Roughness, Breathiness, Asthenia, Strain
      (GRBAS). Method: The Mandarin version of the CAPE-V tool was translated from the
      validated English version with phonemic adaptations, content adjustment, and
      scale modification. Sixty dysphonic, 20 normal, and 20 repeated voice samples
      were included in this study. Ten of these were used for preassessment training;
      the remaining 90 were evaluated using the Mandarin CAPE-V and GRBAS for
      comparison of their interrater and intrarater reliabilities. Results: Intrarater
      reliability was measured by Pearson r for the CAPE-V and Spearman rho for the
      GRBAS. Average CAPE-V Pearson r ranged from 0.80 for strain to 0.91 for overall
      severity, compared with average GRBAS Spearman rho of 0.83 for strain to 0.89 for
      asthenia. Interrater reliability was measured by an intraclass coefficient (ICC).
      Average CAPE-V ICCs ranged from .57 for pitch to .81 for overall severity,
      compared with average GRBAS ICCs of .60 for asthenia to .83 for grade.
      Conclusions: The Mandarin CAPE-V addresses some limits of the English version. It
      also demonstrates good intrarater and interrater reliability, comparable to those
      of GRBAS.

PMID- 30242390
TI  - Posttraumatic Stress Disorder in Primary Care Practice.

PMID- 30242391
TI  - Examining the Association of Cadmium With Contrast Sensitivity.

PMID- 30242392
TI  - Potential Benefits of Inhaled Nitric Oxide in Pulmonary Hypoplasia in Premature
      Neonates.

PMID- 30242393
TI  - Probiotic Safety-No Guarantees.

PMID- 30242395
TI  - Incorrect Author Surname.

PMID- 30242394
TI  - Hearing Care Access?: Focus on Clinical Services, Not Devices.

PMID- 30242396
TI  - Association of Exfoliation Syndrome With Risk of Indirect Inguinal Hernia: The
      Utah Project on Exfoliation Syndrome.
AB  - Importance: Exfoliation syndrome (XFS) is a systemic connective tissue disease,
      and abnormal connective tissue metabolism is implicated in inguinal hernias (IH).
      Associating XFS with comorbid conditions may illuminate their underlying
      pathophysiology and affect clinical screening and treatment. Exfoliation syndrome
      involves altered systemic extracellular matrix (ECM) homeostasis involving
      elastin metabolism. Hernias occur owing to abnormal ECM synthesis, metabolism, or
      repair. Inguinal hernias involve weakening or rupture of the abdominal/groin
      wall. Objective: To determine an association between patients with XFS and
      patients with IH in Utah, possibly differing between direct or indirect hernia.
      Design, Setting, and Participants: Cross-sectional study in a large health care
      system of Utah hospitals and clinics. Conditional logistic regression odds ratios
      were used to estimate risk of XFS in patients with IH overall and by subtype
      (direct or indirect) compared with control individuals. Codes specific to direct
      and indirect IH with additional medical records review of 186 procedures were
      used to classify IH subtypes that were not prespecified. Bootstrap resampling
      with jackknife estimation used to calculate 95% confidence intervals. The model
      accounted for matching on sex and age and adjusted for body mass index and
      tobacco use. Population-based sample using medical records from 1996 to 2015 that
      identified 2594 patients 40 years or older on January 1, 1996, with surgical IH
      repair and 12 966 random control patients with no IH history matched 5:1 on sex
      and birth year. Data were analyzed between September 10, 2017, and October 23,
      2017. Main Outcomes and Measures: Exfoliation syndrome outcome defined by
      diagnosis codes for XFS or exfoliation glaucoma from 1996 to 2015. Results:
      Participants were primarily white (2532 of 2594 patients, [96.1%]; 12 454 of 12
      966 control individuals [97.6%]) and non-Hispanic (2396 of 2594 patients
      [92.4%]); 250 participants were women (9.6%). Of study participants, 22 patients
      with IH and 43 control individuals were diagnosed as having XFS, respectively.
      Patients with IH had a 2.3-fold risk for an XFS diagnosis compared with control
      individuals (95% CI, 1.4-3.5; P = .03), and XFS risk with indirect IH appeared
      especially pronounced. Conclusions and Relevance: Inguinal hernia was associated
      with an increased risk of XFS in this Utah population. Further work is needed to
      understand the pathophysiology, genetics, and environmental factors contributing
      to both diseases.

PMID- 30242397
TI  - Total Medicare Costs Associated With Diagnosis and Treatment of Prostate Cancer
      in Elderly Men.
AB  - Importance: Localized prostate cancer diagnosis and treatment among elderly men
      who are not likely to benefit represents a potential source of low-value health
      care services. Objective: To quantify the costs to the Medicare program
      associated with detection and treatment of prostate cancer among elderly men in
      the United States. Design, Setting, and Participants: This nationwide, population
      based, retrospective cohort study uses the Surveillance, Epidemiology, and End
      Results (SEER)-Medicare linked database to identify men 70 years or older
      diagnosed with localized prostate cancer between 2004 and 2007 and to ascertain
      Medicare costs associated with diagnosis and workup, treatment, follow-up, and
      morbidity management of the disease. National Medicare costs were estimated using
      per-person costs, stage-adjusted prostate cancer incidence rates by age from SEER
      2007 through 2011, and 2010 Census population estimates by age. Main Outcomes and
      Measures: Estimated costs to the Medicare program overall, and in each (mutually
      exclusive) category related to diagnosis and workup, treatment, follow-up, and
      morbidity management. Results: This nationwide, population-based, retrospective
      cohort study included 49 692 men with nonmetastatic prostate cancer from the SEER
      Medicare database (all participants were 70 years or older; 25 981 [52.3%] were
      76 years or older). The median per-patient cost within 3 years after prostate
      cancer diagnosis was $14 453 (interquartile range [IQR], $4887-$27 899). The
      majority of this cost was attributable to treatment costs (median, $10 558; IQR,
      $1990-$23 718). Patients with a Gleason score of 6 or lower who pursued initial
      conservative management (no treatment within 12 months of diagnosis) had a 3-year
      median total cost of $1914 per patient. The estimated total 3-year cost to the
      Medicare program associated with the annual detection of prostate cancer in men
      70 years or older is approximately $1.2 billion. Increasing active surveillance
      use in those with Gleason score of 6 or lower could reduce this cost by $320
      million. Conclusions and Relevance: There is substantial cost to the Medicare
      program associated with the diagnosis and treatment of localized prostate cancer
      among elderly men in the United States, despite the fact that these men are
      unlikely to die of prostate cancer. The majority of costs are related to
      treatment. Reducing provision of low-value health care services among this
      patient population could result in significant health care savings.

PMID- 30242398
TI  - Is Improved Insurance Coverage a Fleeting Opportunity?

PMID- 30242399
TI  - Review: In hypertension, intensive BP goals reduce CV events; self vs office BP
      measures do not improve BP at 12 mo.

PMID- 30242400
TI  - Guideline: 11 professional organizations made 106 recommendations for management
      of high blood pressure in adults.

PMID- 30242401
TI  - Guideline: USPSTF recommends against PSA screening except in men 55 to 69 years
      who express a preference for it.

PMID- 30242403
TI  - As-needed budesonide-formoterol was noninferior to maintenance budesonide for
      exacerbations in mild asthma.

PMID- 30242402
TI  - Review: Liberal oxygen increases mortality in acutely ill adults compared with
      conservative oxygen therapy.

PMID- 30242404
TI  - As-needed budesonide-formoterol better controlled mild asthma vs terbutaline, but
      maintenance budesonide was better.

PMID- 30242406
TI  - In ANCA-associated vasculitis in remission, tailored vs fixed-schedule rituximab
      did not differ for relapse at 28 months.

PMID- 30242405
TI  - In embolic stroke of undetermined source, rivaroxaban vs aspirin did not reduce
      recurrence and increased bleeding.

PMID- 30242407
TI  - Aerobic and strength training did not improve cognitive function in mild to
      moderate dementia.

PMID- 30242408
TI  - The Xpert HCV Viral Load Finger-Stick point-of-care test was accurate for
      detecting HCV RNA.

PMID- 30242409
TI  - Colonoscopy and Colorectal Cancer Mortality.

PMID- 30242410
TI  - Colonoscopy and Colorectal Cancer Mortality.

PMID- 30242411
TI  - Underutilization of Glucagon in the Prehospital Setting.

PMID- 30242412
TI  - Underutilization of Glucagon in the Prehospital Setting.

PMID- 30242413
TI  - Underutilization of Glucagon in the Prehospital Setting.

PMID- 30242414
TI  - Literacy-Adapted Cognitive Behavioral Therapy Versus Education for Chronic Pain.

PMID- 30242415
TI  - Literacy-Adapted Cognitive Behavioral Therapy Versus Education for Chronic Pain.

PMID- 30242416
TI  - Hidden Curricula, Ethics, and Professionalism.

PMID- 30242417
TI  - Hidden Curricula, Ethics, and Professionalism.

PMID- 30242419
TI  - Correction: Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale.

PMID- 30242420
TI  - Murky Water.

PMID- 30242418
TI  - Hidden Curricula, Ethics, and Professionalism.

PMID- 30242422
TI  - Web Exclusive. Annals Consult Guys - Pros and Cons of Therapy to Increase Bone
      Mineral Density.

PMID- 30242421
TI  - Web Exclusive. Annals for Hospitalists Inpatient Notes - Managing Acute Pain in
      the Hospital in the Face of the Opioid Crisis.

PMID- 30242423
TI  - Web Exclusive. Annals On Call - Oral Pharmacologic Therapy in Type 2 Diabetes:
      Choosing Therapy Wisely.

PMID- 30242424
TI  - Annals for Educators - 18 September 2018.

PMID- 30242425
TI  - Annals for Hospitalists - 18 September 2018.

PMID- 30242426
TI  - Allergic-like contrast media reaction management in children.
AB  - The use of contrast materials as part of imaging examinations is common in
      children of all ages, as these compounds increase image contrast, lesion
      detection and lesion characterization. Though modern iodinated, gadolinium-based
      and ultrasound microbubble contrast materials generally are quite safe, acute
      physiological and allergic-like reactions are possible. The majority of acute
      contrast reactions in children are mild and self-limited; however, life
      threatening reactions can occur. It is our obligation as radiologists to
      recognize and manage these adverse reactions. The objective of this article is to
      review the frequency, manifestations and appropriate treatment of acute contrast
      reactions in the pediatric population.

PMID- 30242430
TI  - [Recurrent bleeding of a duodenal ulcer in a 55-year-old man after heart
      transplantation].
AB  - Duodenal ulcers are most often caused by Helicobacter pylori (HP) infection,
      followed by nonsteroidal anti-inflammatory drugs and hypoperfusion.
      Posttransplant lymphoproliferative disorder (PTLD) occurs in about 1-6.3% of
      patients with a heart transplant under immunosuppression therapy. Up to 25% of
      cases of PTLD have gastrointestinal involvement. Due to a wide spectrum of
      clinical symptoms and pathological entities, the diagnosis can be challenging. We
      report the case of a 55-year-old man 12 years after receiving a heart transplant
      being treated with immunosuppressive agents (tacrolimus) who presented with
      recurrent bleeding from peptic duodeni. Immunohistochemistry revealed a rare
      Epstein-Barr-virus-associated polymorphic PTLD. Rarely, PTLD can manifest only
      with isolated lesions of the duodenal bulb. The course was progressive, going
      from an incidental finding requiring transfusion anemia to a perforation within 1
      month. Repeated endoscopic interventions were unsuccessful. After a surgical
      intervention the patient died in the course of multiple organ failure.
      Retrospectively, a reduction of immunosuppression in polymorphic PTLD would have
      been a treatment option.

PMID- 30242429
TI  - Abnormal changes in functional connectivity between the amygdala and frontal
      regions are associated with depression in Alzheimer's disease.
AB  - PURPOSE: The aim of the present study was to investigate the functional
      connectivity (FC) of Alzheimer's disease patients with depression (D-AD) based on
      an amygdalar seed using resting-state functional magnetic resonance imaging (rs
      fMRI). METHODS: Twenty-one non-depressed AD (nD-AD) patients and 21 D-AD patients
      underwent rs-fMRI. The Hamilton Depression Rating Scale and Neuropsychiatric
      Inventory were used to evaluate the severity of depression. The amygdala was used
      as the seed for FC analysis. The FC differences between the two groups were
      evaluated by two-sample t tests, and the correlation of FC changes with
      depressive severity was analyzed by Pearson correlational analysis. RESULTS:
      Compared with the nD-AD patients, D-AD patients had increased FC values between
      the amygdala and orbitofrontal cortex and decreased FC values among the amygdala,
      medial prefrontal cortex, and inferior frontal gyrus. CONCLUSION: These data
      suggest that abnormal amygdala-prefrontal FC may be an important characteristic
      of AD patients with depression.

PMID- 30242428
TI  - FDG-PET imaging to detect and characterize underlying causes of fever of unknown
      origin: an unavoidable path for the foreseeable future.

PMID- 30242427
TI  - The influence of phasic alerting on multisensory temporal precision.
AB  - The relationship between attention and multisensory integration has attracted the
      attention of many researchers but remains a topic of debate. As a mechanism that
      regulates the intensity of attention, little is known regarding whether and how
      phasic alerting affects multisensory perception. Three experiments and warning
      cues were employed to investigate the influence of phasic alerting on
      multisensory temporal processing. Experiments 1 and 2 used a temporal order
      judgement task and a simultaneity judgement task with audiovisual target stimuli
      presented at varying stimulus onset asynchronies. Experiment 3 further adopted a
      dual task to generate a new estimate of participants' performance. Although these
      tasks differ in terms of the required cognitive mechanisms, decreased just
      noticeable difference scores in trials with warning cues consistently indicated
      that participants under phasic alerting had enhanced multisensory temporal
      precision. The point of subjective simultaneity values differed among the three
      tasks, suggesting that the influence of phasic alerting on perceptual deviation
      might be modulated by specific task demands. Experiment 4 adopted a strict method
      to verify that the mechanisms by which warning cues facilitate multisensory
      temporal precision are most likely transient general arousal rather than temporal
      expectancy. There is a close relationship between multisensory integration and
      some neurodevelopmental disorders. Considering that phasic alerting may heighten
      attentional capacity, future research could explore the potential medical
      interventions for the patients with relatively limited attention resources.

PMID- 30242432
TI  - Biopolymer-Based Composite Materials Prepared Using Ionic Liquids.
AB  - Biopolymer-based composite materials have many potential applications in
      biomedical, pharmaceutical, environmental, biocatalytic, and bioelectronic
      fields, owing to their inherent biocompatibility and biodegradability. When used
      as solvents, ionic liquids can be used to fabricate biopolymers such as
      polysaccharides and proteins into various forms, including molded shapes, films,
      fibers, and beads. This article summarizes the processes for preparing biopolymer
      based composite materials using ionic liquids. The processes include biopolymer
      dissolution using ionic liquids, regeneration of the biopolymer by an anti
      solvent, formation of shapes, and drying of the regenerated biopolymer. In
      particular, the preparation and applications of biopolymer blend-based composite
      materials containing two or more biopolymers are addressed.

PMID- 30242431
TI  - [Transition medicine-structural solutions].
AB  - Young adults suffering from chronic diseases represent a critical subgroup of
      patients that after reaching legal age have to be transferred to the colleagues
      from adult medicine. Thus in this patient group two evident problems come
      together: first, the adolescence phase that presents a challenge for any young
      adult and second, the transition to the novel structure and environment of adult
      medicine. It has been recognized for Germany that there are significant deficits
      for this transition phase. These deficits have already been addressed by other
      countries through the introduction of so-called transition clinics. In this
      article, we will summarize the challenges of this transition phase and the
      resulting points and needs that will have to be addressed by a structured program
      for transition. As an example, the Berliner TransitionsProgramm (BTP) will be
      presented where a framework structure is provided that allows for the transition
      of various chronic diseases. The BTP accompanies the transition process for a two
      year time period by providing a framework structure consisting of transition
      consultations, a transition booklet, a structured summary of the previous disease
      course as well as a case manager who assures that the included patients stay
      within the program and do not get lost to assure treatment continuity. In
      addition, the program succeeded, at least from some insurance companies, in
      obtaining financial reimbursement for this time-consuming effort. Thus in our
      view, the BTP functions as role model for transition medicine in Germany.

PMID- 30242434
TI  - Correction to: Biosynthesis and production of quercitols and their application in
      the production of pharmaceuticals: current status and prospects.
AB  - The published online version contains mistake in the chemical structure of scyllo
      inosose in Fig. 5 and Fig. 7. The correct configuration of 1-hydroxyl group in
      scyllo-inosose should have been the same to myo-inositol.

PMID- 30242433
TI  - Uterine prolapse: a hidden tragedy of women in rural Nepal.
AB  - Uterine Prolapse (UP) is a major cause of mortality and morbidity among women in
      low-income countries like Nepal. More than 1 million women in Nepal suffer from
      this condition and most of them belong to the reproductive age. The cause and
      consequence for UP in Nepalese women is mainly gender discrimination. Early
      marriage, multiple births, lack of skilled birth attendants during delivery,
      continuous work throughout their pregnancies and soon after giving birth are the
      risk factors and causes of UP. It affects many aspects of a woman's quality of
      life, which ranges from physical discomfort, psychological, social and sexual
      lifestyle restrictions. Lack of knowledge of casual and preventative measures and
      perception of UP as normal phenomenon is the important barriers to access to
      treatment. Strong, effective and comprehensive strategies should address this
      underlying discrimination including socio-cultural discrimination, which could
      empower women to control their exposure to UP.

PMID- 30242435
TI  - CipA-mediating enzyme self-assembly to enhance the biosynthesis of pyrogallol in
      Escherichia coli.
AB  - Pyrogallol is a valuable phenolic compound and displays various physiological and
      pharmaceutical functions. Chemical synthesis of pyrogallol suffered from many
      issues, including environmental pollution, high cost, and low yield. Here, to
      address the above drawbacks, an artificial pathway for de novo pyrogallol
      production was established and this pathway only needed two exogenous enzymes
      (Y385F/T294A PobA and 3,4-dihydroxybenzoic acid decarboxylase (PDC)). Y385F/T294A
      PobA is a mutant of PobA which is a hydroxylase from Pseudomonas aeruginosa,
      while PDC is a decarboxylase from Klebsiella pneumoniae subsp. pneumoniae. First,
      the conversion efficiency of PDC was tested and 1800 +/- 100 mg/L pyrogallol was
      generated from 4 g/L gallic acid (GA). Subsequently, assembly of the whole
      pathway enabled 33 +/- 6 mg/L pyrogallol production from simple carbon sources.
      After that, based on the assembling property of CipA (a hydrophobic protein) and
      to enhance the hydroxylation of 3,4-dihydroxybenzoic acid, CipA was employed to
      organize its fusion (Y385F/T294A PobA) into protein crystalline inclusions
      (PCIs). Remarkably, the formation of CipA-Y385F/T294A PobA PCIs increased the
      pyrogallol production to 60 +/- 6 mg/L, a 1.8 +/- 0.4-fold higher value as
      compared to the strain without enzyme self-assembly. Additionally, the titer of
      pyrogallol was enhanced to 80 +/- 1 mg/L through yeast extract concentration
      optimization. This work not only realizes the biosynthesis of pyrogallol from
      renewable carbon sources but also demonstrates that using CipA-mediating enzyme
      self-assembly could reinforce the hydroxylation efficiency of Y385F/T294A PobA,
      resulting in the enhancement of pyrogallol production.

PMID- 30242436
TI  - [An aortic patch enables a safe revascularization of all diseased visceral
      arteries].

PMID- 30242437
TI  - [Surgical treatment options for cervical paragangliomas].
AB  - The therapies available for the rare tumor entity of cervical paraganglioma (PG)
      are currently undergoing a paradigm shift. The treatment of choice for small
      carotid body tumors, malignant and active endocrine tumors is surgical resection;
      however, for locally advanced carotid body tumors and vagal PG, surgical therapy
      should be critically evaluated. Due to the immediate proximity of these
      hypervascularized tumors to the caudal cranial nerves, there is a risk of severe
      nerve damage with a significant impairment of quality of life after resection,
      particularly for locally advanced cervical PG, emphasizing further the importance
      of a restrictive surgical strategy. External radiotherapy can provide an
      equivalent primary therapeutic option with respect to the rate of recurrence and
      is accompanied by a lower morbidity. The slow rate of tumor progression and the
      multifocality of the familial variant of cervical PG or significant comorbidities
      in older, asymptomatic patients warrant a less aggressive treatment strategy for
      these tumors. When a wait and scan approach is implemented, a closely monitored
      radiological and clinical re-evaluation is of upmost importance. In a
      multidisciplinary approach the following critical points require consideration
      before a therapy is implemented,: size and location of the tumor, progression
      rate, genetic background, patient age and general condition, relevant
      comorbidities, the presence of synchronous PG and/or vasoactive catecholamine
      producing tumors. Although best practice algorithms for the treatment of cervical
      PG have already been devised, recent innovative developments have led to more
      patient-tailored, individualized treatment approaches.

PMID- 30242438
TI  - [Modern wound treatment-from best practice to innovation].
AB  - According to the Research Group for Primary Medical Care (PMV), approximately
      890,000 people in Germany were suffering from a chronic wound in 2012. This
      corresponds to a prevalence of 1.1%. Ulcus cruris, diabetic ulcers and decubital
      ulcers are among the most frequent causes of chronic wounds (57-80%). The
      guarantee for successful wound care is based on a good understanding of the
      physiology of the wound healing process. A disorder of the phase-like course can
      lead to complications, delays or suspension of wound healing. There are many
      reasons for pathological wound healing including infections, oxygen deficiency
      and non-phase-adapted wound care. In addition to established wound products,
      innovative products such as dermal matrixes, cold plasma therapy and platelet
      rich plasma represent promising therapeutic alternatives for non-healing chronic
      wounds.

PMID- 30242440
TI  - Cellular Interactions in the Intestinal Stem Cell Niche.
AB  - Epithelial cells are one of the most actively cycling cells in a mammalian
      organism and therefore are prone to malignant transformation. Already during
      organogenesis, the connective tissue (mesenchyme) provides instructive signals
      for the epithelium. In an adult organism, the mesenchyme is believed to provide
      crucial regulatory signals for the maintenance and regeneration of epithelial
      cells. Here, we discuss the role of intestinal myofibroblasts, alpha-smooth
      muscle actin-positive stromal (mesenchymal) cells, as an important regulatory
      part of the intestinal stem cell niche. Better understanding of the cross-talk
      between myofibroblasts and the epithelium in the intestine has implications for
      advances in regenerative medicine, and improved therapeutic strategies for
      inflammatory bowel disease, intestinal fibrosis and colorectal cancer.

PMID- 30242439
TI  - Assessment of the Detrimental Impact of Polyvalent Streptophages Intended to be
      Used as Biological Control Agents on Beneficial Soil Streptoflora.
AB  - Streptophages are currently being investigated to control potato common scab,
      however, since a majority of streptophages are reported to be polyvalent, their
      potential to infect beneficial soil streptomycetes during the application process
      may have unintended consequences. To test this hypothesis, two phytopathogenic
      fungi, namely Fusarium solani and Rhizoctonia solani, were tested for their
      detrimental effect on the test crop wheat (Triticum aestivum cv. Gutha). F.
      solani caused a significant root weight reduction (34%) in the wheat plant and
      therefore was tested further in the pot trials with actinomycetes present. Sixty
      seven streptomycete isolates from a Tasmanian potato farm were screened for their
      antifungal abilities against the two phytopathogenic fungi. Four actinomycetes
      found to be strongly antifungal were then tested for their disease-protective
      abilities against F. solani in pot trials again using wheat. Addition of the
      streptomycetes into the container media protected the plants against F. solani,
      indicating that streptomycetes have a disease-suppressive effect. A further pot
      trial was conducted to evaluate whether these beneficial streptomycete species
      would be affected by streptophage treatment and subsequently result in an
      increased risk of fungal infections. When streptophages were added to the pots,
      the shoot and root growth of wheat declined by 23.6% and 8.0%, respectively, in
      the pots with the pathogenic fungus compared to the control pots. These
      differences might suggest that removal of antifungal streptomycetes by polyvalent
      phages from plant rhizosphere when biocontrol of plant pathogenic streptomycetes
      (e.g. Streptomyces scabiei) is targeted might encourage secondary fungal
      infections in the farm environment. The presented data provide preliminary
      evidence that streptophage treatment of pathogenic streptomycetes may lead to an
      aggravated disease risk by soil-borne fungal pathogens when naturally present
      antagonists are removed. As a result, extensive farm site trials are required to
      determine the long-term detrimental impact of polyvalent streptophage treatments
      on beneficial soil streptoflora.

PMID- 30242441
TI  - Prevalence of gingival recession after orthodontic treatment of infraversion and
      open bite.
AB  - PURPOSE: Aim of the present study was to investigate the prevalence of gingival
      recession and related factors in teeth with low occlusal function (open bite and
      infraversion) after orthodontic treatment. METHODS: From January 2014 to December
      2017, 403 patients received orthodontic treatment. Their gingival recession and
      related factors before and after treatment were retrospectively analyzed.
      RESULTS: The prevalence of gingival recession in patients with infraversion and
      open bite after orthodontic treatment were 80.6 and 75.0%, respectively; these
      values were 43.4 and 47.5% before treatment, respectively. Notably, the Miller
      index of gingival recession increased after orthodontic treatment (P < 0.05). The
      risk of gingival recession in patients with infraversion or open bite after
      orthodontic treatment was remarkably higher than the risk in other patients (odds
      ratio [OR] = 16.712 and 5.073, respectively); the gingival recession rate was
      related to treatment with tooth extraction (OR = 2.043), as well as gingival
      biotype (OR = 0.341) and gingival index (GI) before orthodontic treatment (OR =
      97.404; P < 0.05). CONCLUSIONS: Patients with these two types of low occlusal
      function are more likely to exhibit gingival recession after orthodontic
      treatment. Moreover, the prevalence of gingival recession after orthodontic
      treatment is higher among patients who have undergone tooth extraction during
      orthodontic treatment, and among those who exhibit thin gingival biotype and high
      gingival index before orthodontic treatment.

PMID- 30242442
TI  - Diagnosis and Clinical Course of Three Adolescents with Amiodarone-Induced
      Hyperthyroidism.
AB  - Amiodarone-induced hyperthyroidism is a known side effect of amiodarone
      treatment. In the pediatric population, long-term amiodarone treatment is rarely
      indicated because of its severe side effects including thyroid function
      impairment. Treatment is therefore restricted to therapy-resistant arrhythmias.
      In the literature, scarce data are available on the management and therapy of
      amiodarone-induced thyroid dysfunction at a young age. We present three
      adolescent patients developing amiodarone-induced thyrotoxicosis in the months
      after amiodarone therapy. A latency period for thyroid dysfunction has been
      described in adulthood but was not previously reported in pediatric patients. The
      gap between amiodarone treatment and the development of symptoms and the
      diagnosis of hyperthyroidism was between 3 and 10 months. In two patients,
      hyperthyroidism was transient and resolved without treatment. These two patients,
      one boy and on girl, were almost asymptomatic. In contrast, in one male patient
      overt and severe hyperthyroidism developed. We began treatment with thiamazole
      without benefit. Control of hyperthyroidism was achieved under prednisone
      treatment, which was continued for 9 months. Clinical evaluation proved an
      amiodarone-induced destructive thyroiditis in this patient. Amiodarone-induced
      thyroid dysfunction is frequent also in pediatric patients with long-term
      amiodarone treatment. Patients and clinicians should be aware of the impact of
      amiodarone on thyroid function during and also in the months and maybe years
      after treatment. Careful follow-up is needed, as symptoms might be associated
      with the underlying cardiac disease in these patients. Amiodarone-induced
      thyrotoxicosis often resolves without treatment but can be challenging in some
      cases.

PMID- 30242443
TI  - [Plate-assisted segmental bone transport with a lengthening nail and a plate : A
      new technique for treatment of tibial and femoral bone defects].
AB  - BACKGROUND: Distraction osteogenesis represents an effective procedure for
      treatment of bone defects from various causes (e.g. trauma, malignancy,
      congenital and infection). In the past the available procedures were practically
      exclusively external. PRINCIPLES: In the plate-assisted segmental bone transport
      (PABST) procedure a commercially available motorized intramedullary lengthening
      nail is used for segment transport. The transport segment is transported along a
      bone plate, which is responsible for maintaining the position of the proximal and
      distal main fragments. SURGICAL TECHNIQUE: In staged sequences, a plate spanning
      the defect is placed. A lengthening nail is inserted in an antegrade or
      retrograde direction and a vascularized transport segment is created with an
      osteotomy. Bone transport is initiated at 1.0 mm a day. The transport segment is
      pulled or pushed into place, depending on the location of the bone void. In due
      time, a docking procedure is performed and full weight bearing is allowed.
      Supplementary lengthening can be initiated at docking or in a separate procedure.
      In smaller defects the gap is closed immediately over the plate and the bone is
      lengthened by the nail in the opposite end of the defect. CONCLUSION: The
      presented method is a valuable addition to the armamentarium for treatment of
      bone defects. The main advantages are the avoidance of external fixation
      (fixation wires, Schanz screws) and the creation of physiological bone
      substitute. Vital soft tissues are essential for a good outcome. With appropriate
      management (systematic debridement, local and systemic administration of
      antibiotics and free soft tissue flaps), this method can be a solution to even
      complex reconstructive problems.

PMID- 30242445
TI  - [Data content of the TraumaRegister DGU(r) : Results of a random sample control].
AB  - BACKGROUND: Registries are becoming increasingly more important in clinical
      research. The TraumaRegister DGU(r) of the German Society for Trauma Surgery
      plays an excellent role with respect to the care of severely injured patients.
      AIM: Within the framework of this investigation the quality of data provided by
      this registry was to be verified. MATERIAL AND METHODS: Certified hospitals
      participating in the TraumaNetzwerk DGU(r) of the German Society for Trauma
      Surgery are obliged to submit data of treated severely injured patients to the
      TraumaRegister DGU(r). Participating hospitals have to undergo a re-certification
      process every 3 years. Within the framework of this re-audit, data from 5 out of
      8 randomly chosen patient cases included in the registry are controlled and
      compared to the patient files of the certified hospital. In the present
      investigation discrepancies concerning data provided were documented and the
      pattern of deviation was analyzed. RESULTS: The results of 1075 re-certification
      processes carried out in 631 hospitals including the documentation of 5409
      checked patient cases from 2012-2017 were analyzed. The highest number of
      discrepancies detected concerned the documented time until initial CT (15.8%) and
      the lowest concerned the discharge site (3.2%). The majority of data sheets with
      discrepancies showed deviations in only one out of seven checked parameters.
      Interestingly, large trauma centers with a high throughput of severely injured
      patients showed the most deviations. CONCLUSION: The present investigation
      underlines the importance of standardized checks concerning data provided for
      registries in order to be able to guarantee an improvement in entering data.

PMID- 30242444
TI  - [Optimization of criteria for activation of trauma teams : Avoidance of
      overtriage and undertriage].
AB  - INTRODUCTION: Severely injured patients are supposed to be admitted to hospital
      via the trauma room. Appropriate criteria are contained in the S3 guidelines on
      the treatment of patients with severe/multiple injuries (S3-GL); however, some of
      these criteria require scarce hospital resources while the patients then often
      clinically present as uninjured. There are tendencies to streamline the trauma
      team activation criteria (TTAC); however, additional undertriage must be avoided.
      A study group of the emergency, intensive care medicine and treatment of the
      severely injured section (NIS) is in the process of optimizing the TTAC for the
      German trauma system. MATERIAL AND METHODS: In order to solve the objective the
      following multi-step approach is necessary: a) definition of patients who
      potentially benefit from TTA, b) verification of the definition in the
      TraumaRegister DGU(r) (TR-DGU), c) carrying out a prospective, multicenter study
      in order to determine overtriage and undertriage, thereby validating the
      activation criteria and d) revision of the current TTAC. RESULTS: This article
      summarizes the consensus criteria of the group assumed to be capable of
      identifying patients who potentially benefit from TTA. These criteria are used to
      test if TTA was justified in a specific case; however, as the TTCA of the S3-GL
      are not fully incorporated into the TR-DGU dataset and because cases must also be
      considered which were not subject to trauma room treatment and therefore were not
      included in the TR-DGU, it is necessary to perform a prospective full survey of
      all individuals in order to be able to measure overtriage and undertriage.
      CONCLUSION: Currently, the TR-DGU can only provide limited evidence on the
      quality of the TTAC recommended in Germany. This problem has been recognized and
      will be solved by conducting a prospective DGU-supported study, the results of
      which can be used to improve the TR-DGU dataset in order to enable further
      considerations on the quality of care (e. g. composition and size of the trauma
      team).

PMID- 30242446
TI  - Cone-beam CT measurements of distal tibio-fibular syndesmosis in asymptomatic
      uninjured ankles: does weight-bearing matter?
AB  - OBJECTIVE: To evaluate the influence of weight-bearing (WB) load in standard
      axial ankle syndesmotic measurements using cone beam CT (CBCT) examination of
      asymptomatic uninjured ankles. MATERIALS AND METHODS: In this IRB approved,
      prospective study, patients with previous unilateral ankle fractures were
      recruited. We simultaneously scanned the injured ankles and asymptomatic
      contralateral ankles of 27 patients in both WB and NWB modes. For this study,
      only asymptomatic contralateral ankles with normal plain radiographs were
      included. Twelve standardized syndesmosis measurements at two axial planes (10 mm
      above the tibial plafond and 5 mm below the talar dome) were obtained by two
      expert readers using a custom CBCT viewer with the capability for geometric
      measurements between user-identified anatomical landmarks. Inter-reader
      reliability between two readers was obtained using the intra-class correlation
      coefficient (ICC). We compared the WB and NWB measurements using paired t test.
      RESULTS: Significant agreement was observed between two readers for both WB and
      NWB measurements (p <0.05). ICC values for WB and NWB measurements had a range of
      50-95 and 31-71 respectively. Mean values of the medial clear space on WB images
      (1.75, 95% confidence interval [95% CI]: 1.6, 1.9) were significantly lower than
      on NWB images (2.05, 95% CI: 1.8, 2.2) measurements (p <0.001). There was no
      significant difference between the remaining WB and NWB measurements. CONCLUSION:
      Measurements obtained from WB images are reliable. Except for the medial clear
      space, no significant difference in syndesmotic measurements were observed during
      the WB mode of CBCT acquisition, implying that the tibio-fibular relationship
      remains unchanged when the physiological axial weight-bearing load is applied.

PMID- 30242447
TI  - Normal meniscal dimensions at different patient ages-MRI evaluation.
AB  - OBJECTIVE: The purpose of this work is to evaluate the normal meniscal and tibial
      dimensions in relation to age and gender in different children using conventional
      MRI sequences. MATERIALS AND METHODS: Morphometric measurements of the menisci
      were retrospectively performed on knee MRIs of children (< 18 years). All knee
      MRIs over a 7-year period were collected. Exclusion criteria included: prior knee
      surgery or diseases involving the knee joint. A total of 186 children were
      included, 110 boys and 76 girls, with a mean age of 8.2 years (range, 0.3-17.8
      years). Menisci and tibial measurement changes with age and gender as well as
      differences between the medial and lateral menisci were evaluated. RESULTS: The
      medial menisci measurements increased with age (p value < 0.001). The lateral
      menisci measurements increased with age (p value < 0.001), except for the coronal
      meniscal width (p = 0.084). Coronal and sagittal percentage of meniscal coverage
      of the tibia decreased with age (p < 0.001). Medial menisci have greater sagittal
      width and anterior horn height than lateral menisci (p value < 0.001). Lateral
      menisci are larger in their coronal width and height, and sagittal posterior horn
      height in comparison to medial menisci (p < 0.001). CONCLUSIONS: Menisci increase
      in all dimensions in correlation with age; except in the coronal meniscal width,
      which is a useful dimension to diagnose discoid meniscus on MRI, based on this,
      it would seem that the currently published size criteria, based on adults, could
      be applicable to children. The tibia has a faster rate dimension increase in
      correlation with age in comparison to the menisci.

PMID- 30242449
TI  - Correction to: Complement in the pathogenesis of Alzheimer's disease.
AB  - The presentation of Fig. 2 was incorrect.

PMID- 30242450
TI  - Anti-cancer immunotherapy: breakthroughs and future strategies.

PMID- 30242448
TI  - The burden of musculoskeletal disorders in Mexico at national and state level,
      1990-2016: estimates from the global burden of disease study 2016.
AB  - : Worldwide, musculoskeletal (MSK) disorders are the second cause of living with
      disability. According to our data, in Mexico, MSK conditions are an important
      cause of disability, at national and state level. Preventive actions promoted by
      health systems to reduce the burden of MSK disorders are essential. INTRODUCTION:
      We describe premature mortality and disability due to musculoskeletal (MSK)
      disorders in Mexico at national and state level from 1990 to 2016. METHODS: Using
      data from the global burden of disease study 2016 (GBD 2016), we present rates
      and trends in years of life lost (YLLs), years lived with disability (YLDs), and
      disability-adjusted life years (DALYs) caused by MSK disorders in Mexico by state
      from 1990 to 2016. The burden of MSK disorders was computed using standard GBD
      methodology. To compare the burden of MSK disorders across the country, states
      were grouped by sociodemographic index (SDI). RESULTS: In Mexico, MSK disorders
      were the 3rd and 17th greatest cause of YLDs and YLLs in 2016, respectively,
      accounting for 1.95 million (95% UI 1.4-2.5) DALYs. Among all MSK disorders, low
      back and neck pain had the highest all-ages DALYs rate and represented 3.6% of
      total DALYs. All-ages YLLs and YLDs rates of MSK disorders were 234 and 37%
      higher in females (YLLs 102.2, 95% UI 79.9-110.7; YLDs 1677.9, 95% UI 1213.5
      2209.4) than in males (YLLs 30.6, 95% UI 28.3-34.0; YLDs 1224.7, 95% UI 887.2
      1608.3), respectively. Northern and high SDI states had higher rates of MSK
      disorders in comparison with southern and low SDI states. Only 16% of YLDs caused
      by all MSK disorders could be attributed to risk factors currently assessed in
      GBD. CONCLUSION: MSK conditions are an important cause of premature mortality and
      disability. Researcher engagement and cross-sectorial actions to address the
      burden of MSK disorders are essential.

PMID- 30242451
TI  - Inferior Vena Cava Filters in the Asymptomatic Chronically Occluded Cava: To
      Remove or Not Remove?
AB  - Risks of IVC filter insertion are numerous but include IVC stenosis or thrombosis
      and may result in caval occlusion. Acute IVC occlusion is almost always
      symptomatic, and treatment can be aggressive such as catheter-directed
      thrombolysis or conservative such as anticoagulation. The more challenging cohort
      of patients is those where there has been chronic complete occlusion of the IVC
      without symptoms, sometimes only identified at the time of routine filter
      retrieval. We explore the available evidence and discuss different management
      approaches in this circumstance ranging from aggressive to conservative. However,
      given that the overall incidence of filter-related complications is very low, at
      this stage we find no compelling evidence to support aggressive management
      without symptoms.

PMID- 30242452
TI  - Tunnel osteolysis post-ACL reconstruction: a systematic review examining select
      diagnostic modalities, treatment options and rehabilitation protocols.
AB  - PURPOSE: The purpose of this systematic review was to (1) identify the optimal
      diagnostic modality for tunnel widening in skeletally mature patients; (2)
      identify potentially modifiable risk factors for tunnel widening, such as graft
      type, and (3) determine what elements of a post-operative rehabilitation program
      exert the most influence on TW. METHODS: The electronic databases MEDLINE,
      EMBASE, PubMed, and Cochrane Library were searched from database inception to
      January 2018. Studies that discussed tunnel widening following anterior cruciate
      ligament reconstruction (ACLR) of skeletally mature patients and written in
      English were included. Descriptive statistics, such as means, ranges, and
      measures of variance (e.g. standard deviations, 95% confidence intervals (CI))
      are presented where applicable. RESULTS: 103 studies (6,383 patients) were
      included. Plain radiographs were the most commonly used diagnostic modality, but
      radiographs on average required 10 months longer than CT and 2 months longer on
      average than MRI to diagnose tunnel widening after ACLR. Although CT was the
      least commonly used modality, it was the shortest time to diagnose tunnel
      widening at 9.5 months after ACLR. Bone-patellar tendon-bone (BPTB) allograft had
      the largest average tunnel widening overall. BPTB autograft had the lowest
      average tunnel widening overall. Double-bundle hamstring graft configuration had
      a lower average tunnel widening than single-bundle configuration. Rehabilitation
      protocols after ACLR that used a full weight-bearing prescription in
      rehabilitation showed a greater average femoral tunnel widening than partial
      weight-bearing, and partial weight-bearing showed a greater average tibial tunnel
      widening than full weight-bearing. CONCLUSIONS: Based on this systematic review
      and the descriptive data evaluated, CT demonstrated a time of 9.5 months on
      average from ACLR to diagnosing tunnel osteolysis post-ACLR. With respect to
      graft types, double-bundle hamstring autografts reported lower average femoral
      and tibial TW than single-bundle hamstring autografts. BPTB autografts reported
      the lowest average TW and BPTB allograft the largest average TW of all the
      grafts. Furthermore, extension-locked bracing had the lowest TW of all the brace
      protocols. Lastly, several other surgical technical parameters influencing tunnel
      osteolysis remain to be determined. No definitive recommendations can be made at
      this time due to the high heterogeneity of data and the lack of comparative
      studies analysed in this systematic review. LEVEL OF EVIDENCE: IV.

PMID- 30242453
TI  - Highly variable tibial tubercle-trochlear groove distance (TT-TG) in
      osteoarthritic knees should be considered when performing TKA.
AB  - PURPOSE: The tibial tubercle-trochlear groove distance (TT-TG) is an established
      measurement to assist diagnosis and treatment of patellofemoral instability.
      However, little is known about the distribution of TT-TG in osteoarthritic knees.
      The purpose of the current study is to investigate the TT-TG in a large cohort of
      osteoarthritic knees and to analyse, in particular, the association of knee
      alignment and TT-TG. METHODS: Data from 962 consecutive patients [455 male, 507
      female; mean age +/- SD 70.8 +/- 9.3 (37-96)] who had undergone 3D-CT and
      preoperative knee planning with validated commercial 3D planning software before
      total knee arthroplasty (TKA) were collected prospectively. The TT-TG, coronal
      hip knee ankle angle (HKA), femoral anteversion (AVF), external tibial torsion
      (ETT), and femorotibial rotation (Rot FT) were analysed. Pearson correlations
      were performed to assess correlations between TT-TG, mechanical axis, and
      rotational parameters (p < 0.05). RESULTS: HKA showed a strong correlation with
      TT-TG (r = 0.488; p < 0.001) with 98 (67.1%) and 45 (30.8%) of valgus knees
      having respective abnormal and pathological TT-TG values. There were no
      significant correlations between parameters of rotational alignment (AVF, ETT,
      Rot FT) and TT-TG. Mean TT-TG was 12.9 +/- 5.6 mm, ranging from 0.0 to 33.7 mm.
      325 (33.8%) of all patients had abnormal (> 15 mm) and 101 (10.5%) had
      pathological (> 20 mm) values. A varus alignment was present in 716 (74.4%) of
      the cases (HKA < - 1.5 degrees ), a neutral alignment in 100 (10.4%), and a
      valgus alignment in 146 (15.2%) (HKA > 1.5 degrees ). CONCLUSION: A wide
      variation of TT-TG values in osteoarthritic knees was shown by our results. There
      was a relevant influence of coronal limb alignment on the TT-TG-the more valgus
      the higher and more pathological the TT-TG. With the aim of having a more
      personalised TKA, the individual TT-TG should be taken into account to improve
      the outcome. LEVEL OF CLINICAL EVIDENCE: III. Retrospective cohort study.

PMID- 30242454
TI  - Knee hyperextension and a small lateral condyle are associated with greater
      quantified antero-lateral rotatory instability in the patients with a complete
      anterior cruciate ligament (ACL) rupture.
AB  - PURPOSE: To identify factors associated with quantified rotatory stability (pivot
      shift phenomenon) in the anterior cruciate ligament (ACL)-injured knee joint.
      METHODS: A consecutive sample of 54 patients who were diagnosed with an ACL
      injury and admitted to our hospital to undergo ACL reconstruction were enrolled
      in this study. Antero-lateral rotatory laxity of the knee joint was quantified
      using a Kinematic Rapid Assessment device (KiRA; Orthokey LTD) under spinal block
      before initiating reconstruction of the ACL. Univariate and multivariate
      regressions were performed assuming relationships between patient characteristics
      (independent variables) and quantified antero-lateral rotatory stability (a
      dependent variable). RESULTS: It was observed that a low BMI (t = - 1.659, n.s.),
      greater passive knee extension angle (t = 2.374, P = 0.023), and a narrower
      lateral femoral condyle width index (t = - 1.712, n.s.) could be candidates
      associated with the antero-lateral rotatory instability, using univariate
      analysis. Employing multivariate analysis controlling for these three variables,
      that the range of passive knee extension was found to be significantly associated
      with antero-lateral rotatory instability in the ACL-injured knee joint (t = 2.21,
      P = 0.035). Patients were then divided into two groups (pivot-shift negative
      versus positive groups) based on the KiRA-documented quantified pivot-shift test.
      Interestingly, 23.3% of patients were pivot-shift negative, even though their ACL
      was confirmed as a complete rupture by arthroscopic observations. The degree of
      passive knee extension was 2.3 +/- 4.5 (mean +/- SD) in the pivot-shift negative
      group, while it was 6.8 +/- 6.6 in the pivot-shift positive group (n.s.). The
      lateral femoral condyle width index was 36.6 +/- 2.0% in the pivot-shift negative
      group, and it was significantly wider than in the pivot-shift positive group
      (33.8 +/- 2.6%, P = 0.0046). Finally, we estimated that the risk of positive
      pivot-shift depends on the degree of knee extension. The logistic regression
      analysis revealed that genu recurvatum significantly increased the odds ratio for
      positive pivot-shift (OR = 3.08, P = 0.047, 95% CI = 1.017-9.350). CONCLUSIONS:
      This study revealed that greater antero-lateral rotatory instability in patients
      with a complete ACL rupture was associated with genu recurvatum and small lateral
      femoral condyle. These factors should be considered as predictors of a poor
      outcome from an ACL reconstruction due to a higher load on the ACL graft, and
      therefore, the attending physicians should modify the treatment strategies
      accordingly. This study indicates that joint hyperlaxity and bone morphology
      contribute to the rotational stability of the knee joint, in addition to the ACL
      and antero-lateral complex (ALC). LEVEL OF EVIDENCE: IV.

PMID- 30242455
TI  - Allograft tendons are a safe and effective option for revision ACL
      reconstruction: a clinical review.
AB  - Revision anterior cruciate ligament reconstruction remains a challenge,
      especially optimising outcome for patients with a compromised knee where previous
      autogenous tissue has been used for reconstruction. Allograft tissue has become a
      recognized choice of graft for revision surgery but questions remain over the
      risks and benefits of such an option. Allograft tendons are a safe and effective
      option for revision ACL reconstruction with no higher risk of infection and
      equivalent failure rates compared to autografts provided that the tissue is not
      irradiated, or any irradiation is minimal. Best scenarios for use of allografts
      include revision surgery where further use of autografts could lead to high donor
      site morbidity, complex instability situations where additional structures may
      need reconstruction, and in those with clinical and radiologic signs of
      autologous tendon degeneration. A surgeon needs to be able to select the best
      option for the challenging knee facing revision ACL reconstruction, and in the
      light of current data, allograft tissue can be considered a suitable option to
      this purpose. Level of evidence IV.

PMID- 30242456
TI  - The Risk of Erectile Dysfunction Following Pelvic Angiographic Embolization in
      Pelvic Fracture Patients: A Nationwide Population-Based Cohort Study in Taiwan.
AB  - BACKGROUND: Pelvic fracture with hypovolemic shock is a known crucial injury in
      trauma patients. Pelvic fracture with vessel injury often leads to hemodynamic
      complications; in a trauma scenario, evidence of other systems being affected is
      often absent. Bleeding cessation and resuscitation are important for these types
      of trauma patients. For this purpose, pelvic angiographic embolization is
      frequently used. Multiple studies have reported that angiographic embolization
      may cause erectile dysfunction (ED) in hemodynamically stable patients with
      pelvic fracture. However, no study has evaluated a large patient cohort with a
      long-term follow-up. We hypothesized that angiographic embolization to control
      bleeding may compromise blood supply to the genitourinary organs or cause
      secondary neurogenic injury that increases the risk of ED. Our goal was to
      evaluate the risk of ED following pelvic fractures in male patients treated with
      pelvic angiographic embolization. METHODS: We used data from the National Health
      Insurance Research Database (NHIRD) from 1997 to 2010 provided by the Bureau of
      National Health Insurance of the Department of Health in Taiwan. We collected
      disease histories from inpatient files. The disease diagnoses were based on the
      International Classification of Diseases (ICD), Ninth Revision, Clinical
      Modification. These data were all deidentified, and we did not contact the
      patients. As such, informed consent was not needed. RESULTS: Eighty-five and
      82,802 patients were included in the case and control cohorts, respectively. All
      patients were aged 15-45, and the proportion of pelvic fracture locations was
      equal between the groups. After investigating the causes of ED among male
      patients aged 15-45 with pelvic fractures using logistic regression analysis in a
      generalized estimating equations model and after adjusting for the influence of
      confounders, we found that these patients had high risks (odds ratio (OR):
      32.637; 95% confidence interval: 14.137-75.346; P < 0.001) of developing ED post
      angiographic embolization. CONCLUSIONS: Male patients in Taiwan with pelvic
      fractures who undergo angiographic embolization to control bleeding have a higher
      risk of ED than those who do not undergo the procedure. Physicians should
      practice caution and inform patients of this connection before the procedure.

PMID- 30242457
TI  - A Propensity Score-matched Comparison Study of Surgical Outcomes in Patients with
      Differentiated Thyroid Cancer After Robotic Versus Open Total Thyroidectomy.
AB  - INTRODUCTION: The aim of this study, from a surgical, oncological, and functional
      perspective, was to identify whether bilateral axillo-breast approach robotic
      total thyroidectomy (RTT) for differentiated thyroid cancer (DTC) has different
      surgical outcomes compared to open total thyroidectomy (OTT). METHODS: Initially,
      796 patients who underwent total thyroidectomy were primarily reviewed and 178
      who were ineligible for analysis were excluded. Propensity score matching
      analysis adjusted for clinicopathological characteristics (sex, age, body mass
      index, extent of central node dissection, tumor size, extrathyroidal extension,
      and thyroiditis) was conducted, with 246 patients in the OTT group matched with
      123 patients in the RTT group. RESULTS: There were no significant differences in
      surgical outcomes in terms of surgical safety and oncological safety between the
      OTT and RTT groups, except in mean operation times (123.51 +/- 32.63 vs. 198.39
      +/- 37.93 min, respectively; P < 0.001). However, the median parathyroid and
      laryngeal function recovery times were shorter in the RTT group than in the OTT
      group [88 +/- 33.09 (95% CI: 23.148-152.852) vs. 100 +/- 16.20 (95% CI: 68.242
      131.768) days; P = 0.044 and 87 +/- 32.40 (95% CI: 23.489-150.511) vs. 118 +/-
      49.50 (95% CI: 20.985-215.015) days; P = 0.002]. CONCLUSIONS: The recovery times
      of laryngeal and parathyroid function were significantly shorter in RTT patients
      than in OTT patients for DTC. To verify a definitive conclusion about the
      superiority of robotic total thyroidectomy in terms of parathyroid and laryngeal
      function recovery, further studies may be necessary.

PMID- 30242458
TI  - Barriers to Timely Presentation of Patients with Surgical Conditions at Tamale
      Teaching Hospital in Northern Ghana.
AB  - BACKGROUND: Improving access to surgical services and understanding the barriers
      to receiving timely care are necessary to save lives. The aim of this study was
      to assess barriers to timely presentation to an appropriate medical facility
      using the Three-Delay model, for patients presenting to Tamale Teaching Hospital,
      in northern Ghana. METHODS: In 2013, patients with delays in seeking surgical
      care were prospectively identified. Pairwise correlation coefficients between
      delay in presentation and factors associated with delay were conducted and served
      as a foundation for a multivariate log-linear regression model. RESULTS: A total
      of 718 patients presented with an average delay of 22.1 months. Delays in
      receiving care were most common (56.4%), while delays in seeking care were seen
      in 52.3% of patients. "Initially seeking treatment at the nearest facility, but
      appropriate care was unavailable" was reported by 56.4% and predicted longer
      delays (p < 0.001). 42.9% of patients had delays secondary to treatment from a
      traditional or religious healer, which also predicted longer delays (p < 0.001).
      On multivariate regression, emergent presentation was the strongest predictor of
      shorter delays (OR 0.058, p = 0.002), while treatment from a traditional or
      religious healer and initially seeking treatment at another hospital predicted
      longer delays (OR 7.6, p = 0.008, and OR 4.3, p  = 0.006, respectively).
      CONCLUSIONS: Barriers to care leading to long delays in presentation are common
      in northern Ghana. Interventions should focus on educating traditional and
      religious healers in addition to building surgical capacity at district
      hospitals.

PMID- 30242459
TI  - Reply to Commentaries on: Opinions on the "Trick" Technique to Reposition the NAC
      in Female-to-Male Transexuals.

PMID- 30242460
TI  - The Effect of Respiration on Breast Measurement Using Three-dimensional Breast
      Imaging.
AB  - BACKGROUND: Three-dimensional (3D) imaging offers new opportunities to enable
      objective and quantitative analysis of the breast. Unlike scanning of rigid
      objects, respiration may be one of the factors that can influence the measurement
      of breast when using 3D imaging. In this study, we aimed to investigate how the
      different respiratory phases affect 3D morphologic and volumetric evaluations of
      the breast. METHODS: We performed preoperative 3D breast imaging at the end of
      expiration (EE) and the end of inspiration (EI). We repeated scans on each
      respiratory phase, taking four scans in total (EE1, EE2 and EI1, EI2). Using
      Geomagic Studio 12 software, measurements from the different respiratory phases
      (EE1 and EI1) were compared for differences in the linear distances of breast.
      Breast volumetric change error (BVCE) was measured between EE1 and EE2 (R1) and
      between EI1 and EI2 (R2). A multilevel model was used to analyze the difference
      of linear-distances parameters between EE1 and EI1 and a paired sample t-test was
      used to analyze the difference between R1 and R2. RESULTS: Our study included 13
      Chinese women (26 breasts) with a mean age of 32.6 +/- 6.3 years. Compared with
      EI, EE showed a longer sternal notch to the level of the inframammary fold and
      shorter nipple to midline (p < 0.05). During EI, breast projection increased by
      0.23 cm (95% CI - 0.39, - 0.08) and breast base width increased by 0.27 cm (95%
      CI - 0.46, - 0.09). The position of the nipple moved by 0.18 cm (95% CI - 0.34, -
      0.03) laterally, 0.41 cm (95% CI 0.18, 0.64) cranially, and 0.71 cm (95% CI -
      0.92, - 0.51) anteriorly. Although there was no significant difference in BVCE
      between EE and EI, the result seen with EE appeared to be more consistent.
      CONCLUSIONS: The results of this study demonstrate that there was no difference
      in breast volume results when patients are in the expiratory or inspiratory state
      during 3D breast imaging. This study, however, holds potential benefits to both
      surgical practice as well as the 3D imaging industry. LEVEL OF EVIDENCE IV: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 30242461
TI  - Measuring Projection of Nasal Tip with Syringe in Rhinoplasty.
AB  - Preoperative and intraoperative assessments are very important for surgeons to
      plan or regulate tip projection. But how to measure the tip projection is a
      difficult problem even with a ruler or on full-size pictures. In this paper, the
      author introduces a method to measure the nasal tip projection with a remodeled
      syringe.Level of Evidence V This journal requires that authors assign a level of
      evidence to each article. For a full description of these evidence-based medicine
      ratings, please refer to the table of contents or the online instructions to
      authors www.springer.com/00266 .

PMID- 30242462
TI  - Orbital Fat Injection: Technique and 5-Year Follow-Up.
AB  - BACKGROUND: Orbital volume loss, early or late, is common after placement of an
      orbital implant or dermis fat graft, and there is currently no satisfactory long
      lasting solution. Hyaluronic fillers are relatively easy to administer but are
      prone to migration and are temporary. Cannula-based orbital fat grafting has not
      gained the status of standard of care because of perceived low likelihood of
      success in the near term. This paper describes a technique for fat volume
      augmentation, its rationale, long-term follow-up, and a description of a
      complication unique to fat grafting in the orbit. METHODS: Ten consecutive
      subjects with acquired anophthalmic enophthalmos were enrolled in two IRB
      (institutional review board)-approved protocols (10.27 and 12.01) undergoing a
      single session of autologous fat grafting to the orbit using a closed blunt
      cannula technique. Preoperative photography and non-contrast MRIs (magnetic
      resonance imaging) were obtained prior, immediately after, and at 1 year after
      injection. Yearly postoperative photography was performed on subjects with
      successful results. RESULTS: Three of five subjects in IRB 10.27 clearly showed a
      clinically apparent increase in orbital volume at 1 year. One subject who failed
      to show improvement also sustained inadvertent injection into three extraocular
      muscles; she subsequently volunteered to enter IRB 12.01. Three of five subjects
      in IRB 12.01 did benefit, showing volume increase at 1 year, including the
      subject who had experienced intramuscular injection in 10.27. One subject in IRB
      12.01 was lost to follow-up. Of the total of ten subjects enrolled, three showed
      no improvement and one was lost to follow-up; six subjects showed volume
      improvement at 1 year with two retaining the correction at 5 years and four
      showing variable diminution over 2-5 years. With the exception of the subject who
      sustained injection into extraocular muscles, none experienced complications.
      CONCLUSION: A modified technique is recommended for orbital fat injection
      distinct from methods used elsewhere in the body. Theoretical limits of
      volumetric enhancement temper expectations in orbital fat grafting and should
      inform surgical planning. Cannula-based orbital fat grafting can be done safely
      and result in a gain of orbital fat volume at 1 year and in some cases up to 5
      years. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 30242464
TI  - A review on crosstalk in myographic signals.
AB  - PURPOSE: Crosstalk in myographic signals is a major hindrance to the
      understanding of local information related to individual muscle function. This
      review aims to analyse the problem of crosstalk in electromyography and
      mechanomyography. METHODS: An initial search of the SCOPUS database using an
      appropriate set of keywords yielded 290 studies, and 59 potential studies were
      selected after all the records were screened using the eligibility criteria. This
      review on crosstalk revealed that signal contamination due to crosstalk remains a
      major challenge in the application of surface myography techniques. Various
      methods have been employed in previous studies to identify, quantify and reduce
      crosstalk in surface myographic signals. RESULTS: Although correlation-based
      methods for crosstalk quantification are easy to use, there is a possibility that
      co-contraction could be interpreted as crosstalk. High-definition EMG has emerged
      as a new technique that has been successfully applied to reduce crosstalk.
      CONCLUSIONS: The phenomenon of crosstalk needs to be investigated carefully
      because it depends on many factors related to muscle task and physiology. This
      review article not only provides a good summary of the literature on crosstalk in
      myographic signals but also discusses new directions related to techniques for
      crosstalk identification, quantification and reduction. The review also provides
      insights into muscle-related issues that impact crosstalk in myographic signals.

PMID- 30242465
TI  - Confocal laser microscopy as novel approach for real-time and in-vivo tissue
      examination during minimal-invasive surgery in colon cancer.
AB  - BACKGROUND: Histological analysis of surgical specimen is the gold standard for
      cancer classification. In particular, frozen histological diagnosis of vague
      peritoneal spots or uncertain excision of tumors plays a crucial role in the
      decision to proceed with or abandon an operation. Confocal laser microscopy (CLM)
      enables in-vivo and real-time high-resolution tissue analysis. This method has
      already been used during endoscopic assessments analyzing transformation of
      esophageal or colon mucosa. We examined whether a CLM device enables to
      distinguish between non-malignant and malignant tissue in vivo and real time and
      enables to assign peritoneal carcinomatosis spots to their primary tumor. In
      addition, we investigated whether the newly developed CLM camera device causes
      any tissue damage. METHODS: CC531 colon carcinoma cells were implanted on the
      serosa side of the colon and intraperitoneally in Wag/Rija rats via laparotomy.
      After 7 days of tumor growth, confocal laser microscopy in vivo was performed by
      re-laparotomy. Images of non-malignant and malignant tissue were characterized in
      terms of specific signal pattern. No fluorescent dye was used. Correlations to
      findings in conventional histology were systematically recorded and described.
      Potential tissue damage was examined by conventional histology. RESULTS: All
      animals survived the operative procedure and could be evaluated 7 days following
      surgery. No unexpected death occurred after surgery. Non-malignant colon is
      defined by small cycles of the microvilli of the colon. There is repetitive
      deregulated structure in colon carcinoma. Peritoneal carcinomatosis showed the
      same structural pattern as in primary colon carcinoma. In all examined cases, it
      was possible to differentiate between peritoneal carcinomatosis spots and non
      malignant peritoneum. The CLM device did not cause any tissue damage.
      CONCLUSIONS: The CLM camera device reported here is feasible to identify
      peritoneal carcinomatosis spots, assign these spots to the primary tumor, as well
      as distinguish between non-malignant and malignant tissue in without using any
      fluorescent dye.

PMID- 30242466
TI  - Parastomal and incisional hernia following laparoscopic/open abdominoperineal
      resection: is there a real difference?
AB  - BACKGROUND: The aim of the present study was to explore incidence and severity of
      parastomal hernia (PSH) formation during the first 2 years after
      open/laparoscopic abdominoperineal resection (APR). METHODS: This was a
      retrospective cohort study conducted in a single institution. All patients who
      underwent laparoscopic/open APR for low rectal cancer within a 10-year study
      period were assessed for study eligibility. RESULTS: In total, 148 patients were
      included in the study (97 patients after laparoscopic APR; 51 patients after open
      APR). There were no statistically significant differences between study subgroups
      regarding demographic and clinical features. The incidence of PSH detected by
      physical examination was significantly higher in patients after laparoscopic APR
      1 year after the surgery (50.5% vs. 19.6%, p < 0.001) and 2 years after the
      surgery (57.7% vs. 29.4%, p = 0.001). The incidence of radiologically detected
      PSH was significantly higher in laparoscopically operated patients after 1 year
      (58.7% vs. 35.3%, p = 0.007) and after 2 years (61.8% vs. 37.2%, p = 0.004). The
      mean diameter of PSH was similar in both study subgroups. The incidence of
      incisional hernia was significantly higher in patients who underwent open APR
      after 1 year (25.5% vs. 7.2%, p = 0.002) and after 2 years (31.3% vs. 7.2%, p <
      0.001). CONCLUSIONS: The risk of PSH development after laparoscopic APR appears
      to be significantly higher in comparison with patients undergoing open APR.
      Higher incidence of PSH should be considered a potential disadvantage of
      minimally invasive approach to patients with low rectal cancer.

PMID- 30242467
TI  - Case report: panic attacks as symptom of aortic regurgitation and aneurysm.

PMID- 30242469
TI  - Estimation of day of death using micro-segmental hair analysis based on drug use
      history: a case of lidocaine use as a marker.
AB  - During investigations of unnatural death, the time of death is generally
      estimated using anatomical examinations. However, it can be difficult to
      accurately determine the day of death, because postmortem changes in the body
      tissues can be greatly affected by the circumstances of the location of the
      corpse. We recently developed a method to estimate the day of drug ingestion,
      using micro-segmental hair analysis based on internal temporal markers (ITMs). In
      this method, ITMs are ingested at a specific time interval before hair collection
      to mark timescales within individual hair strands. A single hair strand is
      segmented at 0.4-mm intervals, corresponding to average daily hair growth. The
      day of drug ingestion is eventually estimated by calculating the distances
      between segments containing the drug and ITMs in a hair strand. In the present
      study, the method was applied to estimate the day of death. A corpse was
      discovered with a documented medical history of lidocaine administration for
      surgery 57 days before the discovery. Micro-segmental analysis of a hair plucked
      from the corpse was performed using lidocaine as an ITM. Lidocaine was detected
      at specific regions in the hair strands. The day of death was estimated using the
      known surgery day, the distance from the hair root to the lidocaine peak in the
      hair strand, and the average hair growth rate. The novel estimation method using
      a hair enabled us to narrow the estimated time range of death up to the day of
      death, unlike the conventional anatomical examination. The micro-segmental hair
      analysis based on drug use history can be extremely helpful in determining the
      time of an unnatural death.

PMID- 30242468
TI  - Consumption of dairy products in relation to the presence of clinical knee
      osteoarthritis: The Maastricht Study.
AB  - PURPOSE: Observational studies showed inverse associations between milk
      consumption and knee osteoarthritis (knee OA). There is lack of information on
      the role of specific dairy product categories. We explored the association
      between dairy consumption and the presence of knee osteoarthritis in 3010
      individuals aged 40-75 years participating in The Maastricht Study. METHODS: The
      presence of knee OA was defined according to a slightly modified version of the
      American College of Rheumatology (ACR) clinical classification criteria. Data on
      dairy consumption were appraised by a 253-item FFQ covering 47 dairy products
      with categorization on fat content, fermentation or dairy type. Multivariable
      logistic regression analyses were performed to estimate odd ratios (ORs) and 95%
      confidence intervals (95%CI), while correcting for relevant factors. RESULTS: 427
      (14%) participants were classified as having knee OA. Significant inverse
      associations were observed between the presence of knee OA and intake of full-fat
      dairy and Dutch, primarily semi-hard, cheese, with OR for the highest compared to
      the lowest tertile of intake of 0.68 (95%CI 0.50-0.92) for full-fat dairy, and
      0.75 (95%CI 0.56-0.99) for Dutch cheese. No significant associations were found
      for other dairy product categories. CONCLUSION: In this Dutch population, higher
      intake of full-fat dairy and Dutch cheese, but not milk, was cross-sectionally
      associated with the lower presence of knee OA. Prospective studies need to assess
      the relationship between dairy consumption, and in particular semi-hard cheeses,
      with incident knee OA.

PMID- 30242470
TI  - Flutter sensitivity in FM bats. Part II: amplitude modulation.
AB  - Bats use echolocation to detect targets such as insect prey. The echolocation
      call of frequency-modulating bats (FM bats) typically sweeps through a broad
      range of frequencies within a few milliseconds. The large bandwidth grants the
      bat high spatial acuity in depicting the target. However, the extremely short
      call duration and the overall low duty cycle of call emission impair the bat's
      capability to detect e.g. target movement. Nonetheless, FM bats constitute more
      than 80% of all echolocating species and are able to navigate and forage in an
      environment full of moving targets. We used an auditory virtual reality approach
      to generate changes in echo amplitude reflective of fluttering insect wings
      independently from other confounding parameters. We show that the FM bat
      Phyllostomus discolor successfully detected these modulations in echo amplitude
      and that their performance increased with the rate of the modulation, mimicking
      faster insect wing-beats. The ability of FM bats to detect amplitude modulations
      of echoes suggests a release from the trade-off between spatial and temporal
      acuity and highlights the diversity of selective pressures working on the
      echolocation system of bats.

PMID- 30242473
TI  - Temporal patterns of ungulate herbivory and phenology of aspen regeneration and
      defense.
AB  - Ungulate herbivory can create strong top-down effects on forest recruitment,
      especially after fire. Defense strategies of tree species against ungulate
      herbivory include escape through vertical growth and resistance through the
      production of defense compounds. Using a four-way fence design and camera traps
      we characterized the differential impacts of ungulate herbivores (deer, elk,
      cattle) on aspen forest recruitment and plant defense responses and how they vary
      depending on the timing of herbivory. Aspen height growth was greatest between
      June and August and ungulate use of aspen was highest in July and August. Three
      years after fire, height of aspen differed among fence treatments with full
      ungulate exclusion > deer-only plots > native ungulate plots > fenceless plots:
      108 +/- 4 cm, 94 +/- 4 cm, 89 +/- 4 cm, and 65 +/- 4 cm, respectively. Fenceless
      plots had the highest rates of removal of apical meristems by the end of 2014 and
      2015 (61% and 53%, respectively). Native ungulate plots, and deer-only plots both
      had similar removal of apical meristems in 2014 (37% and 39%, respectively). The
      highest phenolic glycoside concentrations were associated with an 80% reduction
      in meristem removal and four-fold greater aspen height by the end of summer. Low
      nitrogen was associated with an 86% reduction in apical meristem removal and
      threefold greater aspen height. In conclusion, our study suggests that high
      ungulate abundance can have detrimental impacts on forest recruitment and that
      high aspen defense chemistry and lower leaf N deters ungulate herbivory,
      especially in the late summer.

PMID- 30242474
TI  - Who is legally responsible for deaths caused by air pollution?
AB  - A person's death is deemed unnatural when it is the result of an external force.
      This definition, however, does not apply when the cause of death is a respiratory
      or cardiovascular process triggered by a high concentration of an air pollutant,
      even if other deaths from toxicological causes (poisonings, overdoses, etc.) are.
      The distinction between natural and unnatural cause of death, although not
      internationally standardized, is critical in determining wrongfulness and
      liability, which in turn can have financial and/or legal repercussions. Even
      though the World Health Organization and other medical and scientific
      organizations have shown that air pollution contributes to several million deaths
      every year, there are currently no practical means to determine whether a person
      was subjected to high concentrations of atmospheric pollution before their death;
      indeed, the ability to find evidence of this type of exposition could prove very
      interesting from a forensic standpoint.

PMID- 30242472
TI  - Microsynteny analysis to understand evolution and impact of polyploidization on
      MIR319 family within Brassicaceae.
AB  - The availability of a large number of whole-genome sequences allows comparative
      genomic analysis to reveal and understand evolution of regulatory regions and
      elements. The role played by events such as whole-genome and segmental
      duplications followed by genome fractionation in shaping genomic landscape and in
      expansion of gene families is crucial toward developing insights into
      evolutionary trends and consequences such as sequence and functional
      diversification. Members of Brassicaceae are known to have experienced several
      rounds of whole-genome duplication (WGD) that have been termed as
      paleopolyploidy, mesopolyploidy, and neopolyploidy. Such repeated events led to
      the creation and expansion of a large number of gene families. MIR319 is reported
      to be one of the most ancient and conserved plant MIRNA families and plays a role
      in growth and development including leaf development, seedling development, and
      embryo patterning. We have previously reported functional diversification of
      members of miR319 in Brassica oleracea affecting leaf architecture; however, the
      evolutionary history of the MIR319 gene family across Brassicaceae remains
      unknown and requires investigation. We therefore identified homologous and
      homeologous segments of ca. 100 kb, with or without MIR319, performed comparative
      synteny analysis and genome fractionation studies. We detected variable rates of
      gene retention across members of Brassicaceae when genomic blocks of MIR319a,
      MIR319b, and MIR319c were compared either between themselves or against
      Arabidopsis thaliana genome which was taken as the base genome. The highest
      levels of shared genes were found between A. thaliana and Capsella rubella in
      both MIR319b- and MIR319c-containing genomic segments, and with the closest
      species of A. thaliana, A. lyrata, only in MIR319a-containing segment. Synteny
      analysis across 12 genomes (with 30 sub-genomes) revealed MIR319c to be the most
      conserved MIRNA loci (present in 27 genomes/sub-genomes) followed by MIR319a
      (present in 23 genomes/sub-genomes); MIR319b was found to be frequently lost
      (present in 20 genomes/sub-genomes) and thus is under least selection pressure
      for retention. Genome fractionation revealed extensive and differential loss of
      MIRNA homeologous loci and flanking genes from various sub-genomes of Brassica
      species that is in accordance with their older history of polyploidy when
      compared to Camelina sativa, a recent neopolyploid, where the effect of genome
      fractionation was least. Finally, estimation of phylogenetic relationship using
      precursor sequences of MIR319 reveals MIR319a and MIR319b form sister clades,
      with MIR319c forming a separate clade. An intra-species synteny analysis between
      MIR319a-, MIR319b-, and MIR319c-containing genomic segments suggests segmental
      duplications at the base of Brassicaceae to be responsible for the origin of
      MIR319a and MIR319b.

PMID- 30242475
TI  - A new rocuronium formulation not causing vascular pain in a flexor reflex model
      of anesthetized rats.
AB  - PURPOSE: Intravenous administration of the brand formulation of rocuronium
      bromide, currently used as a muscle relaxant, has been associated with vascular
      pain accompanied by withdrawal movements of the arm and wrist. The purpose of
      this study was to identify the cause of vascular pain induced by the brand
      formulation and to develop a new rocuronium formulation, not causing vascular
      pain, using a vascular pain-evoked flexor reflex response model of anesthetized
      rats. METHODS: A rat flexor reflex model, monitored by electromyography, was used
      to evaluate a flexor reflex response as the index of vascular pain. A catheter
      for drug administration was inserted into the superficial caudal epigastric
      artery. A needle electrode was inserted into a muscle in the femoral area to
      obtain an electromyogram (EMG) value. The integrated EMG values obtained after
      the administration of each test drug were compared to the baseline value and
      quantified. RESULTS: The acetate buffer contained in the solvent could cause
      flexor reflex response. Furthermore, the flexor reflex response increased in an
      acid concentration-dependent manner. Based on these results, we prepared a new
      rocuronium formulation using a low-acid-concentration buffer solution and found
      that it decreased the integrated EMG value in the rat model. The integrated EMG
      value acquired using the brand formulation was reduced by pretreatment with the
      TRPA1 channel inhibitor. CONCLUSION: Our findings suggest that the high acid
      concentration in the brand formulation buffer solution is the cause of vascular
      pain. The rocuronium formulation developed using a low-acid-concentration buffer
      solution might help eliminate vascular pain in the clinic.

PMID- 30242476
TI  - Tumor-specific genetic aberrations in cell-free DNA of gastroesophageal cancer
      patients.
AB  - The applicability of liquid biopsies is studied intensively in all types of
      cancer and analysis of circulating tumor DNA (ctDNA) has recently been
      implemented clinically for mutation detection in lung cancer. ctDNA may provide
      information about tumor quantity and mutations present in the tumor, and as such
      have many potential applications in diagnosis and treatment of cancer. It has
      been suggested that ctDNA analysis may overcome the issue of intra-tumor
      heterogeneity faced by tissue biopsies and serve as an additional diagnostic
      tool. Furthermore, liquid biopsies are potentially helpful for monitoring of
      treatment response as well as detection of minimal residual disease and relapse.
      Gastroesophageal cancers (GEC) have high mortality rates and the majority of
      patients present with advanced stage at diagnosis or succumb due to disease
      recurrence even after radical resection of the primary tumor. Biomarkers that can
      help optimize treatment strategy are thus highly desirable. The present study is
      a review of published data on ctDNA in GEC patients. We identified 25 studies in
      which tumor-specific genetic aberrations were investigated in plasma or serum and
      discuss these in relation to the methods applied for ctDNA analysis. The methods
      used for ctDNA detection greatly influence the sensitivity of the analysis and,
      therefore, the potential clinical applications. We found that studies of ctDNA in
      GEC, although limited in number, are promising for several applications such as
      genetic profiling of tumors and monitoring of disease progression. However, more
      studies are needed to establish if and how this analysis can be clinically
      implemented.

PMID- 30242477
TI  - Monosodium glutamate for accidental, retrospective, and medical dosimetry using
      electron spin resonance.
AB  - The risk of a radiation episode has increased in the last years due to several
      reasons. In case of a nuclear incident, as with the use of an improvised nuclear
      device, determination of the radiation doses received by the victims is of utmost
      importance to define the appropriate medical treatment or to monitor the late
      effects of radiation. Dose assessment in case of accidents can be performed using
      commonplace materials found in the accident area. In this paper, the dosimetric
      properties of monosodium glutamate are investigated by electron spin resonance
      spectroscopy (ESR), for retrospective and accidental dosimetry. The spectroscopic
      parameters were optimized to achieve higher signal intensity and better signal-to
      noise ratio. As a result, the lowest detectable dose was 0.1 Gy, and monosodium
      glutamate showed a linear dose-response curve for doses ranging from 0.1 Gy to 10
      kGy. The dosimetric signal was monitored from minutes right after irradiation,
      until 1 year. No changes in the signal intensity were observed over this period,
      meaning that doses could be assessed immediately after radiation exposure and can
      still be reconstructed long after the accident. This property also implies that
      late effects due to victim's radiation exposure could be better monitored and
      understood. ESR signal intensity for samples irradiated with a photon energy
      below 100 keV was decreased by only 27% and no dose-rate dependence was noticed.
      Therefore, the ability to measure doses as low as 0.1 Gy, the high stability of
      the dosimetric signal, as well as independence on dose rate, tissue equivalence,
      low-cost, and wide commercial availability make monosodium glutamate a very good
      dosimetric material not only for retrospective and accidental but also for
      medical dosimetry.

PMID- 30242478
TI  - Appendiceal neoplasm risk associated with complicated acute appendicitis-a
      population based study.
AB  - PURPOSE: Appendiceal tumors are rare, but high neoplasm rates have been reported
      at interval appendectomy after periappendicular abscess. Non-operative management
      of uncomplicated acute appendicitis has shown promising results. The data on
      appendiceal tumor incidence and presentation among acute appendicitis patients is
      limited, especially in patient cohorts differentiating between uncomplicated and
      complicated acute appendicitis. Objective was to assess appendiceal tumor
      incidence and tumor association to appendicitis in patients with uncomplicated
      and complicated acute appendicitis. METHODS: This nationwide population-based
      registry study was conducted from 2007 to 2013. The Finnish Cancer Registry and
      the National Institute for Health Registry were used to combine data on all
      appendiceal tumors and acute appendicitis diagnosis with medical reports
      evaluated at eight study hospitals. RESULTS: Altogether, 840 appendiceal tumors
      were identified, and out of these, 504 patient reports were reviewed, including
      472 patients in this study. Tumor was diagnosed at appendectomy for suspected
      acute appendicitis in 276 patients (58%). In the whole study, histologically
      acute appendicitis and tumor were both present in 53% (n = 250), and out of
      these, 41% (n = 102) were complicated and 59% (n = 148) uncomplicated acute
      appendicitis. The associated tumor risk was significantly higher in complicated
      acute appendicitis compared with uncomplicated cases (3.24% vs. 0.87%, p <
      0.001). Overall tumor prevalence among acute appendicitis patients was 1.24%.
      CONCLUSIONS: Appendiceal tumor prevalence in acute appendicitis was low. Tumor
      risk was significantly higher in complicated acute appendicitis compared with
      uncomplicated acute appendicitis. The risk of missed appendiceal tumors related
      to antibiotic therapy of uncomplicated acute appendicitis is very low.

PMID- 30242479
TI  - Chromosome painting in meiosis reveals pairing of specific chromosomes in
      polyploid Solanum species.
AB  - Analysis of chromosome pairing has been an important tool to assess the genetic
      similarity of homologous and homoeologous chromosomes in polyploids. However, it
      is technically challenging to monitor the pairing of specific chromosomes in
      polyploid species, especially for plant species with a large number of small
      chromosomes. We developed oligonucleotide-based painting probes for four
      different potato chromosomes. We demonstrate that these probes are robust enough
      to monitor a single chromosome throughout the prophase I of meiosis in polyploid
      Solanum species. Cultivated potato (Solanum tuberosum, 2n = 4x = 48) is an
      autotetraploid. We demonstrate that the four copies of each potato chromosome
      pair as a quadrivalent in 66-78% of the meiotic cells at the pachytene stage.
      Solanum demissum (2n = 6x = 72) is a hexaploid and has been controversial
      regarding its nature as an autopolyploid or allopolyploid. Interestingly, no
      hexavalent pairing was observed in meiosis. Instead, we observed three
      independent bivalents in 83-98% of the meiotic cells at late diakinesis and early
      metaphase I for the four chromosomes. These results suggest that S. demissum has
      evolved into a cytologically stable state with predominantly bivalent pairing in
      meiosis.

PMID- 30242480
TI  - Authors' response to Commentary on "Role of barium swallow pharyngoesophagography
      in the management of globus pharyngeus".

PMID- 30242481
TI  - Angulation of the ossified stylohyoid complex and Eagle syndrome.

PMID- 30242482
TI  - Synthetic Opioids.
AB  - Opioid abuse has been a global menace for centuries, but the proliferation of
      synthetic opioids and their use within this current decade have created epidemic
      level harms in some countries. According to the United Nations Office on Drugs
      and Crime, almost 12 million years were estimated loss of "healthy" life
      resulting in premature death and disability attributable to global opioid abuse
      just in 2015. Law enforcement and regulatory authorities have been particularly
      challenged abating the spread of synthetic opioids because soon after controlling
      the currently recognized abused opioids, their structures are tweaked, and new
      entities replace them. Drug racketeers have most often exploited the fentanyl
      phenylpiperidine structure in this regard, but non-fentanyl-like and classical
      morphinan-like structures have been pirated as well. A growing number of
      anecdotal reports identify respiratory depression induced by these newer
      synthetic opioids to be especially refractive to reversal by antagonists, with
      consequently high levels of lethality. This review examines three of these
      synthetic opioids representing three chemical classes (U-47700, MT-45, and
      acetylfentanyl) that have emerged to be of such menace that they have been
      brought under international control in recent years and addresses factors that
      could make synthetic opioids especially untreatable by opioid antagonists.

PMID- 30242483
TI  - Bound state solutions of Schrodinger equation with modified Mobius square
      potential (MMSP) and its thermodynamic properties.
AB  - We solved the Schrodinger equation with the modified Mobius square potential
      model using the modified factorization method. Within the framework of the Greene
      Aldrich approximation for the centrifugal term and using a suitable
      transformation scheme, we obtained the energy eigenvalues equation and the
      corresponding eigenfunction in terms of the hypergeometric function. Using the
      resulting eigenvalues equation, we calculated the vibrational partition function
      and other relevant thermodynamic properties. We also showed that the modified
      Mobius square potential can be reduced to the Hua potential model using
      appropriate potential constant values.

PMID- 30242484
TI  - When finite becomes infinite: convergence properties of vibrational spectra of
      oligomer chains.
AB  - We present a computational study of convergence properties of vibrational IR and
      Raman spectra for a series of increasingly long units of polyethylene, cis- and
      trans-polyacetylenes, and polyynes. Convergent behavior to the spectra of
      infinitely long polymers was observed in all cases when chains reached lengths of
      approximately 60 carbon atoms, both with respect to the positions of the bands
      and to their intensities. The vibrational spectra of longer chains are
      practically indistinguishable. The convergence rate depends on the degree of the
      pi conjugation in a studied system: Vibrational spectra for oligoethylenes
      converge noticeably faster than the spectra for the conjugated systems. The
      slowest convergence is observed for skeletal motions of the oligomer chains,
      which may require more than a hundred carbon atoms in the chain to show
      deviations smaller than 1 cm-1 to the corresponding solid-state calculations. The
      results suggest that the boundary between the properties of finite and infinite
      molecular systems fades away for a surprisingly small number of atoms.

PMID- 30242486
TI  - Investigation of net unidirectional ring shuttling in a chemically fueled
      [2]catenane.
AB  - Switchable rotaxanes and catenanes are environmentally responsive mechanically
      interlocked molecular architectures (MIMAs). Because of their ability to exhibit
      reversible and controllable motion in response to environmental stimuli,
      switchable rotaxanes and catenanes show promise for the advancement of nanoscale
      devices. Herein we present a study of the first 'autonomous' catenane-based motor
      (Wilson et al. in Nature 534(7606):235-240, 2016) through a domestically
      developed simulation tool designed to capture the basic physics/chemistry of the
      ring shuttling process. The results of the simulation are consistent with the
      experimentally inferred unidirectional motion in the catenane motor. The factors
      that affect ring shuttling are explored, and the features of the system that
      could potentially be modified to influence the rate and directional preference of
      ring shuttling are reported.

PMID- 30242485
TI  - Biochemical and microbiological activity of soil contaminated with o-cresol and
      biostimulated with Perna canaliculus mussel meal.
AB  - The choice of the study subject was a consequence of the growing interest in
      volatile organic compounds which are strongly dispersed in the environment. The
      knowledge of o-cresol's capability for being broken down by bacteria should be
      supplemented by studies aimed at determining the biochemical and microbiological
      activity of soils. o-Cresol was applied at the following rates: 0, 0.1, 1, 10,
      and 50 mg of o-cresol kg-1 d.m. of soil to determine its effect on the biological
      properties of soil. The activity of dehydrogenases, catalase, urease, acid
      phosphatase, alkaline phosphatase, arylsulfatase, and beta-glucosidase, the eight
      groups of microorganism counts, was determined in soil samples after 45 days and
      the barley yield was determined. Preventive biostimulation with Perna canaliculus
      mussel meal, illustrated by means of the index of fertility (IF), was conducted
      in order to eliminate the adverse effect of o-cresol. The soil and crop
      resistance index (RS) was used to illustrate the response of barley, and R:S-the
      rhizosphere effect index was used to determine the effect of the crop on the
      enzymatic activity of soil. o-Cresol had a beneficial effect on the biological
      activity of soil at an acceptable rate of 0.1 and 1 mg kg-1 d.m. of soil, and it
      became its inhibitor after being applied at 10 and 50 mg kg-1 d.m. of soil, which
      also brought about a decrease in the resistance of spring barley. Dehydrogenases
      are the most sensitive, and catalase is the least sensitive, to the pressure of o
      cresol in soil. Mussel meal can be recommended as a biostimulator of soil
      fertility. It also eliminated the negative effect of o-cresol on its biological
      activity.

PMID- 30242487
TI  - Epigenetic signature of MAOA and MAOB genes in mental disorders.
AB  - Epigenetic processes such as DNA methylation are considered key mechanisms at the
      crossroads between genetics and environment in the etiology of mental disorders.
      The monoamine oxidases A and B (MAOA/MAOB) are prime candidates for the
      investigation into the role of DNA methylation in mental disorders, given their
      pivotal role in the metabolism of monoamines and as pharmacological targets of
      potent antidepressant drugs such as tranylcypromine, phenelzine or moclobemide.
      The present mini-review aims at summarizing and critically discussing the growing
      body of the literature supporting a role of DNA methylation of the MAOA gene
      promoter/exon I/intron I region and its interaction with environmental factors in
      several mental disorders, i.e., anxiety disorders, depression, posttraumatic
      stress disorder, substance use disorder, conduct disorder/antisocial personality
      disorder, borderline personality disorder and schizophrenia, as well as some
      pilot data on MAOB methylation in smokers and patients with borderline
      personality disorder. Furthermore, first evidence for MAOA methylation to be
      involved in treatment response prediction and as a potential mechanistic
      correlate of fear extinction is presented. Altered MAOA gene DNA methylation
      emerges as a possible pathogenetically relevant epigenetic mechanism in mental
      disorders. Given robust replication and further functional characterization, MAOA
      methylation patterns might serve as a peripheral biomarker of disease risk and
      treatment response informing preventive and personalized therapeutic approaches
      in the future.

PMID- 30242488
TI  - Intra-monsoonal variation of zooplankton population in the Sundarbans Estuarine
      System, India.
AB  - The present study was conducted during July 2013 (early phase of monsoon or EM)
      and September 2013 (later phase of monsoon or LM) to ascertain the intra
      monsoonal variation on zooplankton, by selecting 15 study stations in the river
      Saptamukhi, one of the main estuaries in the Sundarbans Estuarine System (SES).
      In 2013, SES experienced an unusually high monsoonal rainfall also exacerbated by
      cloud burst event at Himalayan region (upper stretches of SES) which tremendously
      increased the river runoff. The present work was aimed to decipher the effect of
      this unusual precipitation during the monsoon season on zooplankton assemblages
      along with different hydrological parameters. The abundance of zooplankton was
      recorded as lower during EM compared to LM. Altogether, 56 zooplankton taxa were
      identified with copepods forming the predominant population. Thirty-three copepod
      species were reported with 25 calanoid species forming the bulk of the biomass
      followed by 5 and 3 species of cyclopoids and harpacticoid, respectively. A
      combination of multivariate cluster analysis, biotic indices, and canonical
      correspondence analysis revealed noticeable alterations in the zooplankton
      community structure across the spatio-temporal scale. Furthermore, significant
      intra-monsoonal changes in zooplankton population correlated with several
      hydrological parameters were clearly noticed. Paracalanus parvus, Bestiolina
      similis and Oithona similis were observed to be the most dominant copepod species
      in both sampling periods. The result of the present study provides new insight on
      estuarine zooplankton community after unusual rainfall during monsoon season, and
      provides further evidence to support the conservation and management of the SES
      ecosystem.

PMID- 30242489
TI  - Scavenging of hydroxyl, methoxy, and nitrogen dioxide free radicals by some
      methylated isoflavones.
AB  - Free radicals can be scavenged from biological systems by genistein, daidzein,
      and their methyl derivatives through hydrogen atom transfer (HAT), single
      electron transfer (SET), and sequential proton-loss electron-transfer (SPLET)
      mechanisms. Reactions between these derivatives and the free radicals OH., OCH3.,
      and NO2. via the HAT mechanism in the gas phase were studied using the transition
      state theory within the framework of DFT. Solvation of all the species and
      complexes involved in the HAT reactions in aqueous media was treated by
      performing single point energy calculations using the polarizable continuum model
      (PCM). The SET and SPLET mechanisms for the above reactions were also considered
      by applying the Marcus theory of electron transfer, and were found to be quite
      sensitive to geometry and solvation. Therefore, the geometries of all the species
      involved in the SET and SPLET mechanisms were fully optimized in aqueous media.
      The calculated barrier energies and rate constants of the HAT-based scavenging
      reactions showed that the OH group of the B ring in genistein, daidzein, and
      their methyl derivatives plays a major role in the scavenging of free radicals,
      and the role of this OH group in the HAT-based free-radical scavenging decreases
      in the following order: OH. > OCH3. > NO2.. The SPLET mechanism was found to be
      an important mechanism in these free-radical scavenging reactions, whereas the
      SET mechanism was not important in this context.

PMID- 30242490
TI  - Amperometric sensing of ascorbic acid by using a glassy carbon electrode modified
      with mesoporous carbon nanorods.
AB  - Mesoporous carbon nanorods (MCNRs) were prepared from honey as the carbon source
      and by using crab (Brachyuran) shells as the hard template. The unique
      nanostructure of the MCNRs with their uniform mesoporous size, abundant defective
      sites and numerous oxygen-functional groups was characterized by nitrogen
      adsorption-desorption isotherms, X-ray diffraction, Raman spectroscopy, X-ray
      photoelectron spectroscopy and Fourier transform infrared spectroscopy. Cyclic
      voltammograms of a glassy carbon electrode (GCE) modified with MCNRs revel a
      higher peak current density and lower peak potential (-0.03 V vs. Ag/AgCl) for
      ascorbic acid (AA) electrooxidation compared to a conventional GCE and a carbon
      nanotube-modified GCE. Figures of merit for this sensor include (a) a wide linear
      range (10-2770 MUM), (b) high electrochemical sensitivity (216.91 MUA mM-1 cm-2)
      and (c) a low detection limit (2.3 MUM). These compare favorably to the
      respective data for a CNT-modified GCE (50-2150 MUM, 5.20 MUA mM-1 cm-2 and 26.8
      MUM) and a plain GCE (100-2000 MUM, 0.58 MUA mM-1 cm-2 and 54.6 MUM). The
      modified GCE was successfully applied to the determination of AA in (spiked) real
      samples including an injection, soft drinks and fresh lemon juice. Therefore, the
      new sensor can be considered as an affordable tool for electrochemical sensing of
      AA in real samples. Graphical abstract Mesoporous carbon nanorods (MCNRs) were
      prepared by using honey as the carbon source and crab shells as the hard
      template. The MCNRs modified a glassy carbon electrode (MCNRs/GCE) was used for
      the ascorbic acid (AA) detection by amperometry.

PMID- 30242491
TI  - Towards a comprehensive understanding of the Si(100)-2*1 surface termination
      through hydrogen passivation using methylamine and methanol: a theoretical
      approach.
AB  - Using density functional theory, we explored the termination process of Si (100)
      2 * 1 reconstructed surface mechanistically through the dehydrogenation of small
      molecules, considering methyl amine and methanol as terminating reagents. At
      first, both the terminating reagents form two types of adduct through adsorption
      on the Si (100)-2 * 1 surface, one in chemisorption mode and the other via
      physisorption, from which the dehydrogenation process is initiated. By analyzing
      the activation barriers, it was observed that termination of the Si-surface
      through the dehydrogenation is kinetically almost equally feasible using either
      reagent. We further examined in detail the mechanism for each termination process
      by analyzing geometrical parameters and natural population analysis charges. From
      bonding evaluation, it is evident that hydrogen abstraction from adsorbates on
      the Si-surface is asymmetric in nature, where one hydrogen is abstracted as
      hydride by the electrophilic surface Si and the other hydrogen is abstracted as
      proton by the neucleophilic surface Si. Moreover, it was also observed that
      hydride transfer from adsorbate to the Si-surface occurs first followed by proton
      transfer. Overall, our theoretical interpretation provides a mechanistic
      understanding of the Si (100)-2 * 1 reconstructed surface termination by amine
      and alcohol that will further motivate researchers to design different types of
      decorated semiconductor devices. Graphical Abstract Surface termination process
      of Si(100)-2*1 through formation of non-polar Si-H bonds via dehydrogenation of
      methylamine and methanol as terminating reagents.

PMID- 30242492
TI  - Novel loci fsd6.1 and Csgl3 regulate ultra-high fruit spine density in cucumber.
AB  - KEY MESSAGE: Quantitative Trait Loci (QTL) analysis of multiple populations in
      multiple environments revealed that the fsd6.2 locus, which includes the
      candidate gene Csgl3, controls high fruit spine density in natural cucumbers.
      GWAS identified a novel locus fsd6.1, which regulates ultra-high fruit spine
      density in combination with Csgl3, and evolved during cucumber domestication.
      Fruit spine density, a domestication trait, largely influences the commercial
      value of cucumbers. However, the molecular basis of fruit spine density in
      cucumber remains unclear. In this study, four populations were derived from five
      materials, which included three with low fruit spine density, one with high fruit
      spine density, and one with ultra-high fruit spine density. Fruit spine densities
      were measured in 15 environments over a span of 6 years. The distributions were
      bimodal suggesting that fruit spine density is controlled by a major-effect QTL.
      QTL analysis determined that the same major-effect QTL, fsd6.2, is present in
      four populations. Fine mapping indicated that Csgl3 is the candidate gene at the
      fsd6.2 locus. Phylogenetic and geographical distribution analyses revealed that
      Csgl3 originated from China, which has the highest genetic diversity for fruit
      spine density. One novel minor-effect QTL, fsd6.1, was detected in the HR and HP
      populations derived from the cross between 65G and 02245. In addition, GWAS
      identified a novel locus that colocates with fsd6.1. Inspection of a candidate
      region of about 18 kb in size using pairwise LD correlations, combined with
      genetic diversity and phylogenetic analysis of fsd6.1 in natural populations,
      indicated that Csa6G421750 is the candidate gene responsible for ultra-high fruit
      spine density in cucumber. This study provides new insights into the origin of
      fruit spine density and the evolution of high/ultra-high fruit spine density
      during cucumber domestication.

PMID- 30242493
TI  - Fine mapping of a dominant gene conferring resistance to spot blotch caused by a
      new pathotype of Bipolaris sorokiniana in barley.
AB  - KEY MESSAGE: We fine-mapped and physically anchored a dominant gene (Rbs7)
      conferring resistance to spot blotch caused by a new pathotype of Bipolaris
      sorokiniana in a genomic interval of 304 kb on barley chromosome 6H. Spot blotch,
      caused by Bipolaris sorokiniana, is an economically important disease on barley
      in the Upper Midwest region of the USA and Prairie Provinces of Canada. A new
      pathotype (pathotype 7, represented by isolate ND4008) of B. sorokiniana has been
      identified, which is highly virulent on barley cultivars with resistance to other
      pathotypes of the fungus. In this study, we fine-mapped a dominant gene
      conferring resistance to pathotype 7 in the barley line PI 235186. Genetic
      analysis of the F1 and F2 plants from a cross between PI 356741 (highly
      susceptible to ND4008) and PI 235186 (highly resistant to ND4008) indicated that
      a single dominant gene (Rbs7) controls the resistance in PI 235186. This result
      was confirmed by genetic analysis of the F2:3 families and a recombinant inbred
      line (RIL) population derived from the same cross. Bulked segregant analysis
      using simple sequence repeat markers localized Rbs7 on the short arm of
      chromosome 6H. Additional DNA markers were developed from the 6H pseudomolecule
      sequence of barley cv. Morex and mapped to the genomic region carrying Rbs7 using
      the RIL population and F2 recombinants derived from the PI 356741 * PI 235186
      cross. Rbs7 was fine-mapped between two markers (M13.06 and M13.37), which spans
      a physical distance of 304 kb on Morex chromosome 6H. These results provide a
      foundation for future cloning of the resistance gene and development of user
      friendly molecular markers that can be used for development of spot-blotch
      resistant cultivars in barley breeding programs.

PMID- 30242494
TI  - A radiological and anatomic examination of intralaminar screws in the thoracic
      spine-a theoretical feasibility study.
AB  - BACKGROUND: Failure of pedicle screws and anatomical variations which prevent
      pedicle screw implantation make the search for an alternative to pedicle screws
      in thoracic spine surgery necessary. To date, published data have shown that
      intralaminar screws could be a possible way of fixation. Object of this study is
      a systematic examination of the feasibility of lamina screws in the whole
      thoracic spine. METHODS: Fifty females and 50 males (age 20 to 60 years) who
      underwent a polytrauma CT from 2010 to 2012 were randomly selected. Patients with
      injury of the thoracic spine, trauma-independent deformity, or dysplasia of the
      thoracic spine were excluded. A three-dimensional reconstruction of the thoracic
      spine was performed from the data set. The anatomical data of the lamina were
      measured under consideration of the potential trajectory of a laminar screw. The
      caliber of the corresponding pedicle was measured as well. RESULTS: The diameters
      of the lamina show a decline in superior-inferior direction (0.66 cm in T1 to
      0.60 cm in T12 in males, 0.62 to 0.56 cm in females). Diameters of pedicle and
      lamina show no correlation. Twenty percent of the pedicles have a hypoplasia with
      a diameter of less than 0.5 cm. However, in these vertebrae, 62.3% of the laminae
      would be suitable for 0.4-cm lamina screws. Only in 2.75% of the vertebral
      bodies, there was no possibility for intralaminar or pedicle screws. CONCLUSIONS:
      This study shows that it is possible to use intralaminar screws in the thoracic
      spine in most of patients.

PMID- 30242495
TI  - Intrathecal penetration of meropenem and vancomycin administered by continuous
      infusion in patients suffering from ventriculitis-a retrospective analysis.
AB  - BACKGROUND: Vancomycin and meropenem are frequently used as empiric treatment for
      ventriculitis. Penetration into the cerebrospinal fluid (CSF) depends on various
      factors with a high inter-individual variability. Because attaining and
      maintaining adequate concentrations of meropenem and vancomycin in the CSF is
      crucial for their bactericidal effect, we introduced a routine therapeutic drug
      monitoring (TDM) from CSF and serum for both antibiotics. We studied the
      antibiotic penetration into the CSF. METHODS: Patient data including serum and
      CSF concentrations for meropenem and vancomycin were collected in a retrospective
      fashion. Antibiotic CSF penetration ratio was calculated for each patient.
      Antibiotics were administered by continuous infusion aiming for serum target
      concentrations of 20-30 mg/L for vancomycin and 16-32 mg/L for meropenem.
      RESULTS: Twenty-two patients with 36 CSF/serum pairs for meropenem and 43 pairs
      for vancomycin were studied. No patient suffered from renal or liver
      insufficiency. Mean vancomycin serum concentration was 22 +/- 8 mg/L and the mean
      CSF concentration 4.5 +/- 2.6 mg/L. CSF penetration was 20 +/- 11% (coefficient
      of determination (R2) 0.02). For meropenem, the mean serum concentration was 30.7
      +/- 14.9 mg/L, mean CSF concentration 5.5 +/- 5.2 mg/L, and a penetration of 18
      +/- 12%, R2 = 0.42. CONCLUSION: Penetration of meropenem and vancomycin into the
      CSF is low while showing a high interindividual variability. Various patients in
      our study cohort were at risk for insufficient target attainment in CSF.
      Continuous administration of antibiotics under routine TDM appears to be a
      feasible and reasonable approach for optimization of intrathecal drug levels in
      patients suffering from ventriculitis. TDM might guide individual dosing
      adaptation and efforts to predict the CSF penetration of meropenem and vancomycin
      in cases of ventriculitis.

PMID- 30242497
TI  - Salpingectomy compared with tubal ligation during cesarean delivery.

PMID- 30242496
TI  - Intraneural lipomas: institutional and literature review.
AB  - BACKGROUND: Adipose lesions of nerve can be envisioned as a spectrum ranging from
      intraneural/extraneural lipomas to lipomatosis of nerve (LN). We have noticed
      that intraneural lipomas are not as a homogenous group as previously thought and
      demonstrate differences which have clinical implications. To better understand
      intraneural lipomas, we conducted a search of cases at our institution and
      published cases in the world's literature. MATERIALS AND METHODS: Mayo Clinic's
      database was searched between years 1994-2018. Published cases were identified
      using PubMed and Google Scholar databases. Following terms were used: intraneural
      lipoma, lipoma and nerve, lipoma and neuropathy, lipofibroma and nerve,
      fibrolipoma and nerve and neural lipoma as well as lipofibroma and fibrolipoma
      alone. Cases that could be clearly identified as intraneural lipomas by the
      location of the lipoma within the epineurium were included for analysis. These
      cases were then sub-classified as encapsulated intraneural lipomas or hybrid
      intraneural lipomas (demonstrating features of both intraneural/extraneural
      lipomas and LN) based on their characteristics. RESULTS: We identified 12 cases
      at our institution (8 encapsulated, 4 hybrid) and 24 published cases (21
      encapsulated, 3 hybrid). The most commonly affected nerve was median both at our
      institution and in the published cases. Encapsulated cases were found to be
      relatively easy to resect. Hybrid cases demonstrated variable degree of
      interdigitating fat between the fascicles and were relatively difficult to
      resect. CONCLUSION: Intraneural lipomas exist as two separate entities with
      distinct clinical implications. Although rare, this should be taken in account
      when planning surgery. Terminology should be clarified to prevent ambiguity and
      confusion.

PMID- 30242498
TI  - Are we choosing the correct FSH starting dose during controlled ovarian
      stimulation for intrauterine insemination cycles? Potential application of a
      nomogram based on woman's age and markers of ovarian reserve.
AB  - PURPOSE: To evaluate the potential application of a nomogram based on woman's age
      and ovarian reserve markers as a tool to optimize the follicle-stimulating
      hormone (FSH) starting dose in intrauterine insemination (IUI) cycles. METHODS:
      We conducted a retrospective analysis enrolling 179 infertile women undergoing
      controlled ovarian stimulation (COS), followed by IUI. Each woman received an FSH
      starting dose according to clinical decision. After collecting data about COS and
      IUI procedures, we calculated the FSH starting dose according to the nomogram.
      The main outcomes measured were women's baseline characteristics, COS, and
      clinical outcomes. RESULTS: The FSH starting dose calculated by the nomogram was
      significantly lower than the one actually prescribed (p < 0.001), in only 14.8%
      of the cycles nomogram calculated a higher starting dose. When gonadotropin dose
      was decreased during COS, and similarly in case of hyper-response (more than two
      follicles >= 16 mm retrieved), the FSH starting dose calculated by the nomogram
      would have been lower in most of the cases (81.8% and 48.8%, respectively).
      Conversely, when gonadotropin dose was increased during COS and in case of low
      ovarian response (no follicle >= 16 mm retrieved), the FSH starting dose
      calculated by the nomogram would have been lower in most of the cases (64.7% and
      100%, respectively); in these groups median anti-Mullerian hormone (AMH) level
      was 5.62 ng/mL. CONCLUSIONS: The application of this nomogram in IUI cycles would
      lead to a more tailored FSH starting dose and improved cost-effectiveness,
      although in PCOS women, particularly the ones with high AMH, it does not seem
      adequate.

PMID- 30242499
TI  - Preventative effect of celecoxib in dimethylbenz[a]anthracene-induced ovarian
      cancer in rats.
AB  - PURPOSE: The present study investigated the preventive effect of the
      cyclooxygenase (COX)-2 inhibitor, celecoxib, in 7,12-dimethylbenz[a]anthracene
      (DMBA)-induced ovarian cancer in a rat model. METHODS: A diet containing
      celecoxib (1500 ppm) was started 2 weeks before the introduction of DMBA. DMBA
      soaked cotton threads were surgically applied to induce ovarian cancer in female
      Wistar rats. Tumor growth and survival were observed for 24 weeks. RESULTS:
      During the study period, an overall tumor incidence of 97.5% was observed and 65%
      of tumors were ovarian adenocarcinoma. The celecoxib diet significantly reduced
      the incidence and size of DMBA-induced ovarian cancers and significantly improved
      survival of tumor-bearing rats. The preventive effect of celecoxib was associated
      with increased apoptosis. CONCLUSION: DMBA-induced ovarian cancer in rats
      recapitulates many pathophysiological features of the human counterpart. Our
      results provide supportive evidence that celecoxib has a preventive effect on
      development of ovarian cancer in a rat model.

PMID- 30242500
TI  - Phenotype-genotype correlations and emerging pathways in ocular anterior segment
      dysgenesis.
AB  - Disorders of the anterior segment of the eye encompass a variety of clinical
      presentations including aniridia, Axenfeld and Rieger anomalies, primary
      congenital glaucoma, Peters anomaly, as well as syndromal associations. These
      conditions have a significant impact on vision due to disruption of the visual
      axis, and also secondary glaucoma which occurs in over 50% of patients. Ocular
      anterior segment disorders occur due to a complex interplay of developmental,
      embryological and genetic factors, and often have phenotypic overlaps and genetic
      heterogeneity. Here we present a review of the clinical features and genes
      associated with aniridia, Axenfeld and Rieger anomalies, primary congenital
      glaucoma, Peters anomaly, and syndromic forms of these conditions. We also
      highlight phenotype-genotype correlations, recent discoveries with next
      generation sequencing which broaden known phenotypes, and new anterior segment
      genes and pathways. We provide a guide towards genetic diagnosis for clinicians
      investigating patients with anterior segment dysgenesis.

PMID- 30242502
TI  - The genetic architecture of aniridia and Gillespie syndrome.
AB  - Absence of part or all of the iris, aniridia, is a feature of several genetically
      distinct conditions. This review focuses on iris development and then the
      clinical features and molecular genetics of these iris malformations. Classical
      aniridia, a panocular eye malformation including foveal hypoplasia, is the
      archetypal phenotype associated with heterozygous PAX6 loss-of-function
      mutations. Since this was identified in 1991, many genetic mechanisms of PAX6
      inactivation have been elucidated, the commonest alleles being intragenic
      mutations causing premature stop codons, followed by those causing C-terminal
      extensions. Rarely, aniridia cases are associated with FOXC1, PITX2 and/or their
      regulatory regions. Aniridia can also occur as a component of many severe global
      eye malformations. Gillespie syndrome-a triad of partial aniridia, non
      progressive cerebellar ataxia and intellectual disability-is phenotypically and
      genotypically distinct from classical aniridia. The causative gene has recently
      been identified as ITPR1. The same characteristic Gillespie syndrome-like iris,
      with aplasia of the pupillary sphincter and a scalloped margin, is seen in ACTA2
      related multisystemic smooth muscle dysfunction syndrome. WAGR syndrome (Wilms
      tumour, aniridia, genitourinary anomalies and mental retardation/intellectual
      disability), is caused by contiguous deletion of PAX6 and WT1 on chromosome 11p.
      Deletions encompassing BDNF have been causally implicated in the obesity and
      intellectual disability associated with the condition. Lastly, we outline a
      genetic investigation strategy for aniridia in light of recent developments,
      suggesting an approach based principally on chromosomal array and gene panel
      testing. This strategy aims to test all known aniridia loci-including the rarer,
      life-limiting causes-whilst remaining simple and practical.

PMID- 30242503
TI  - Repeatability and reproducibility of FreeSurfer, FSL-SIENAX and SPM brain
      volumetric measurements and the effect of lesion filling in multiple sclerosis.
AB  - OBJECTIVES: To compare the cross-sectional robustness of commonly used volumetric
      software and effects of lesion filling in multiple sclerosis (MS). METHODS: Nine
      MS patients (six females; age 38+/-13 years, disease duration 7.3+/-5.2 years)
      were scanned twice with repositioning on three MRI scanners (Siemens Aera 1.5T,
      Avanto 1.5T, Trio 3.0T) the same day. Volumetric T1-weighted images were
      processed with FreeSurfer, FSL-SIENAX, SPM and SPM-CAT before and after 3D FLAIR
      lesion filling with LST. The whole-brain, grey matter (GM) and white matter (WM)
      volumes were calculated with and without normalisation to the intracranial volume
      or FSL-SIENAX scaling factor. Robustness was assessed using the coefficient of
      variation (CoV). RESULTS: Variability in volumetrics was lower within than
      between scanners (CoV 0.17-0.96% vs. 0.65-5.0%, p<0.001). All software provided
      similarly robust segmentations of the brain volume on the same scanner (CoV 0.17
      0.28%, p=0.076). Normalisation improved inter-scanner reproducibility in
      FreeSurfer and SPM-based methods, but the FSL-SIENAX scaling factor did not
      improve robustness. Generally, SPM-based methods produced the most consistent
      volumetrics, while FreeSurfer was more robust for WM volumes on different
      scanners. FreeSurfer had more robust normalised brain and GM volumes on different
      scanners than FSL-SIENAX (p=0.004). MS lesion filling changed the output of FSL
      SIENAX, SPM and SPM-CAT but not FreeSurfer. CONCLUSIONS: Consistent use of the
      same scanner is essential and normalisation to the intracranial volume is
      recommended for multiple scanners. Based on robustness, SPM-based methods are
      particularly suitable for cross-sectional volumetry. FreeSurfer poses a suitable
      alternative with WM segmentations less sensitive to MS lesions. KEY POINTS: * The
      same scanner should be used for brain volumetry. If different scanners are used,
      the intracranial volume normalisation improves the FreeSurfer and SPM robustness
      (but not the FSL scaling factor). * FreeSurfer, FSL and SPM all provide robust
      measures of the whole brain volume on the same MRI scanner. SPM-based methods
      overall provide the most robust segmentations (except white matter segmentations
      on different scanners where FreeSurfer is more robust). * MS lesion filling with
      Lesion Segmentation Toolbox changes the output of FSL-SIENAX and SPM. FreeSurfer
      output is not affected by MS lesion filling since it already takes white matter
      hypointensities into account and is therefore particularly suitable for MS brain
      volumetry.

PMID- 30242504
TI  - Value of adding dynamic contrast-enhanced MRI visual assessment to conventional
      MRI and clinical assessment in the diagnosis of complete tumour response to
      chemoradiotherapy for rectal cancer.
AB  - PURPOSE: To determine if DCE-MRI adds diagnostic value to the combined use of
      T2WI and DWI-MRI in the determination of clinical complete response (cCR) after
      neoadjuvant treatment (NAT) in patients with locally advanced rectal cancer.
      METHODS AND MATERIALS: In this IRB-approved, HIPAA-compliant retrospective study,
      response was assessed using a 5-point confidence score by T2WI and DWI-MRI only
      ('standard MRI'), then with addition of DCE-MRI. Review of digital rectal exams
      and endoscopy notes produced a clinical overall response score. The reference
      standard was CR by histopathology or cCR determined after a minimum of 18 months'
      follow-up. Diagnostic accuracy and ROC curves were calculated for standard MRI
      and added DCE-MRI (to detect complete or good response), for clinical evaluation
      (to detect CR) and for MRI and clinical methods combined. RESULTS: Of 65 patients
      undergoing NAT, 20 had cCR (31%). Sensitivity, specificity and area under the ROC
      (AUC) were 0.55, 0.87 and 0.69 for clinical evaluation; 0.42, 0.77 and 0.66 for
      standard MRI, and 0.53, 0.76 and 0.68 for added DCE-MRI, respectively. Combined
      clinical evaluation and standard MRI with DCE-MRI resulted in the highest
      specificity of 0.96 and highest AUC of 0.72. CONCLUSION: For the assessment of
      cCR after neoadjuvant therapy using clinical and multi-sequence MRI reading
      strategies, the addition of DCE-MRI increased specificity and PPV, but not
      significantly. KEY POINTS: * The addition of dynamic contrast-enhanced MRI to
      standard MRI, including DWI-MRI, may not significantly improve accuracy of
      response assessment in rectal cancer treatment. * Clinical assessment consisting
      of digital rectal examination and endoscopy is the most accurate standalone test
      to assess response to chemoradiotherapy in rectal cancer. * Combining MRI using
      DWI and DCE with the clinical assessment may potentially improve the accuracy for
      response assessment in rectal cancer.

PMID- 30242501
TI  - Knockout of ush2a gene in zebrafish causes hearing impairment and late onset rod
      cone dystrophy.
AB  - Most cases of Usher syndrome type II (USH2) are due to mutations in the USH2A
      gene. There are no effective treatments or ideal animal models for this disease,
      and the pathological mechanisms of USH2 caused by USH2A mutations are still
      unknown. Here, we constructed a ush2a knockout (ush2a-/-) zebrafish model using
      TALEN technology to investigate the molecular pathology of USH2. An early onset
      auditory disorder and abnormal morphology of inner ear stereocilia were
      identified in the ush2a-/- zebrafish. Consequently, the disruption of Ush2a in
      zebrafish led to a hearing impairment, like that in mammals. Electroretinography
      (ERG) test indicated that deletion of Ush2a affected visual function at an early
      stage, and histological analysis revealed that the photoreceptors progressively
      degenerated. Rod degeneration occurred prior to cone degeneration in ush2a-/-
      zebrafish, which is consistent with the classical description of the progression
      of retinitis pigmentosa (RP). Destruction of the outer segments (OSs) of rods led
      to the down-regulation of phototransduction cascade proteins at late stage. The
      expression of Ush1b and Ush1c was up-regulated when Ush2a was null. We also found
      that disruption of fibronectin assembly at the retinal basement membrane weakened
      cell adhesion in ush2a-/- mutants. In summary, for the first time, we generated a
      ush2a knockout zebrafish line with auditory disorder and retinal degeneration
      which mimicked the symptoms of patients, and revealed that disruption of
      fibronectin assembly may be one of the factors underlying RP. This model may help
      us to better understand the pathogenic mechanism and find treatment for USH2 in
      the future.

PMID- 30242505
TI  - A suprachiasmatic-independent circadian clock(s) in the habenula is affected by
      Per gene mutations and housing light conditions in mice.
AB  - For many years, the suprachiasmatic nucleus (SCN) was considered as the unique
      circadian pacemaker in the mammalian brain. Currently, it is known that other
      brain areas are able to oscillate in a circadian manner. However, many of them
      are dependent on, or synchronized by, the SCN. The Habenula (Hb), localized in
      the epithalamus, is a key nucleus for the regulation of monoamine activity
      (dopamine, serotonin) and presents circadian features; nonetheless, the clock
      properties of the Hb are not fully described. Here, we report, first, circadian
      expression of clock genes in the lateral habenula (LHb) under constant darkness
      (DD) condition in wild-type mice which is disturbed in double Per1-/--Per2Brdm1
      clock-mutant mice. Second, using Per2::luciferase transgenic mice, we observed a
      self-sustained oscillatory ability (PER2::LUCIFERASE bioluminescence rhythmicity)
      in the rostral and caudal part of the Hb of arrhythmic SCN-ablated animals.
      Finally, in Per2::luciferase mice exposed to different lighting conditions (light
      dark, constant darkness or constant light), the period or amplitude of PER2
      oscillations, in both the rostral and caudal Hb, were similar. However, under DD
      condition or from SCN-lesioned mice, these two Hb regions were out of phase,
      suggesting an uncoupling of two putative Hb oscillators. Altogether, these
      results suggest that an autonomous clock in the rostral and caudal part of the Hb
      requires integrity of circadian genes to tick, and light information or SCN
      innervation to keep synchrony. The relevance of the Hb timing might reside in the
      regulation of circadian functions linked to motivational (reward) and emotional
      (mood) processes.

PMID- 30242506
TI  - Expression of radial glial markers (GFAP, BLBP and GS) during telencephalic
      development in the catshark (Scyliorhinus canicula).
AB  - Radial glial cells (RGCs) are the first cell populations of glial nature to
      appear during brain ontogeny. They act as primary progenitor (stem) cells as well
      as a scaffold for neuronal migration. The proliferative capacity of these cells,
      both in development and in adulthood, has been subject of interest during past
      decades. In contrast with mammals where RGCs are restricted to specific
      ventricular areas in the adult brain, RGCs are the predominant glial element in
      fishes. However, developmental studies on the RGCs of cartilaginous fishes are
      scant. We have studied the expression patterns of RGCs markers including glial
      fibrillary acidic protein (GFAP), brain lipid binding protein (BLBP), and
      glutamine synthase (GS) in the telencephalic hemispheres of catshark
      (Scyliorhinus canicula) from early embryos to post-hatch juveniles. GFAP, BLBP
      and GS are first detected, respectively, in early, intermediate and late embryos.
      Expression of these glial markers was observed in cells with radial glia
      morphology lining the telencephalic ventricles, as well as in their radial
      processes and endfeet at the pial surface and their expression continue in
      ependymal cells (or tanycytes) in early juveniles. In addition, BLBP- and GS
      immunoreactive cells morphologically resembling oligodendrocytes were observed.
      In late embryos, most of the GFAP- and BLBP-positive RGCs also coexpress GS and
      show proliferative activity. Our results indicate the existence of different
      proliferating subpopulations of RGCs in the embryonic ventricular zone of
      catshark. Further investigations are needed to determine whether these
      proliferative RGCs could act as neurogenic and/or gliogenic precursors.

PMID- 30242507
TI  - Possible factors associated with sagittal malalignment recurrence after pedicle
      subtraction osteotomy.
AB  - PURPOSE: This retrospective study investigates sagittal alignment after pedicle
      subtraction osteotomy (PSO). The purpose was to investigate factors associated
      with malalignment recurrence. METHODS: Full spine radiographs were analyzed in 66
      patients (average age 54.5 years, follow-up 3.8 years). Measurements were taken
      preoperatively, 3 months postoperatively, at follow-up: SVA C2 and C7, C2-C7
      lordosis, T4-T12 kyphosis, L1-S1 lordosis, PSO lordosis, pelvic incidence, pelvic
      tilt, sacral slope. Follow-up CTs were screened for pseudarthrosis and gas in
      sacroiliac joints. RESULTS: PSO lordosis increased from 11.8 degrees  to 40.8
      degrees  (p < 0.0001) and kept stable. Lumbar lordosis increased from 28.6
      degrees  to 57.7 degrees  (p < 0.0001) and decreased to 49.7 degrees  (p =
      0.0008). Pelvic tilt decreased from 29.2 degrees  to 16.5 degrees  (p < 0.0001)
      and increased to 22.5 degrees  (p < 0.0001). SVA C7 decreased from 105.1 to 35.5
      mm (p < 0.0001) and increased to 64.8 mm (p = 0.0005). Twenty-eight patients
      (42%) had an SVA C7 increase of more than 70 mm in the postoperative course:
      recurrence group. These patients were older: 62.8 years versus 52.3 years (p =
      0.0031). Loss of lordosis was 11.9 degrees  (recurrence group) versus 5.0 degrees
      (non-recurrence group). Eleven patients (17%) had pseudarthrosis. Pelvic
      incidence increased by 9.3 degrees  (recurrence group) versus 3.8 degrees  (non
      recurrence group). In 23 patients (35%), pelvic incidence increased > 10 degrees
      . Gas was evidenced in sacroiliac joints in 22 patients (33%). CONCLUSION:
      Postoperative anterior malalignment recurrence may occur after PSO. Elderly
      patients were at risk of recurrence. Loss of lumbar lordosis linked to
      pseudarthrosis represented another factor. With malalignment recurrence, anterior
      trunk rotation and pelvic retroversion might additionally have augmented moments
      across sacroiliac joints with subsequent ligament laxity and pelvic incidence
      increase. These slides can be retrieved under Electronic Supplementary Material.

PMID- 30242508
TI  - Paget's disease of the lumbar spine: decompressive surgery following 17 years of
      bisphosphonate treatment.
AB  - BACKGROUND: We present a rare case of Paget's disease (PD) with involvement of
      the lumbar spine over a period of 19 years. We discuss the diagnostic process to
      rule out alternative diagnoses and medical and surgical treatment strategies.
      CASE DESCRIPTION: A 58-year-old man first diagnosed with PD in 1998 with solid
      involvement of the 4th lumbar vertebra has been undergoing periodic examinations
      over a period of 18 years. Since then, the patient has been treated
      conservatively with bisphosphonates. When conservative treatment options have
      been exhausted, surgery was indicated due to a progressively reduced ability to
      walk. Surgery with undercutting decompression via laminotomy was performed. PD
      was confirmed by biopsy. Bisphosphonate treatment was continued pre- and
      postoperatively. Follow-up examinations showed an improvement in clinical outcome
      measures. CONCLUSIONS: Conservative treatment remains the gold standard for PD
      with spinal involvement. This patient had been asymptomatic on bisphosphonate
      therapy for almost 17 years, but presented with new onset back pain. In such
      cases, fracture and rare conversion into sarcoma must be ruled out, and biopsy
      should be performed even in the absence of signs of malignancy. Currently, there
      are no clear treatment recommendations available in the literature regarding
      cases of PD with expansive growth and involvement of the spinal canal causing
      neurologic deficits. Furthermore, laminectomy has been shown to cause
      complications in up to 27% of cases with the risk of early postoperative death.
      In contrast, extended laminotomy and undercutting decompression should be
      considered.

PMID- 30242509
TI  - A molecularly imprinted chitosan doped with carbon quantum dots for fluorometric
      determination of perfluorooctane sulfonate.
AB  - A molecularly imprinted polymer (MIP) was fabricated for selective recognition of
      the highly persistent pollutant perfluorooctane sulfonate (PFOS). The MIP was
      prepared from chitosan and doped with fluorescent carbon quantum dots (CQDs). It
      was characterized by fluorescence spectrophotometry, scanning electron
      microscopy, and Fourier transform infrared spectroscopy. The fluorescence of the
      CQDs, best measured at excitation/emission wavelengths of 350/460 nm, is enhanced
      by PFOS, and the effect is much stronger for the MIP than for the nonimprinted
      polymer (NIP). The imprinting factor is 2.75. The method has good specificity
      over sodium dodecyl sulfate (SDS), perfluorooctanoic acid (PFOA), sodium dodecyl
      sulfonate (SDS'), sodium dodecyl benzene sulfonate (SDBS),
      perfluorooctanesulfonyl fluoride (POSF), perfluorobutane sulfonate (PFBS) and 1
      octanesulfonic acid sodium (OSA). Fluorescence increases linearly in the 20-200
      pg.L-1 POSF concentration range in aqueous solution. The method was applied to
      the determination of PFOS in spiked serum and urine samples. The limits of
      detection are 66 and 85 pg.L-1 for serum and urine samples respectively. The
      recoveries ranged from to 81-98%, with relative standard deviations in the range
      of 1.8-8.2%. Compared with LC-MS/MS, this assay is more convenient since the
      material can be prepared flexibly and the method can be applied on-site.
      Graphical abstract Schematic of the fabrication of a molecularly imprinted
      chitosan hydrogel doped with CQDs for selective fluorometric determination of
      PFOS. a. The photo of chitosan hydrogel. b, c, d, e represents the hydrogel
      observed under UV lamp. b', c', d', e' represents the inner structure of hydrogel
      bead.

PMID- 30242511
TI  - Small-Molecule Inhibitors of PARPs: From Tools for Investigating ADP-Ribosylation
      to Therapeutics.
AB  - Over the last 60 years, poly-ADP-ribose polymerases (PARPs, 17 family members in
      humans) have emerged as important regulators of physiology and disease. Small
      molecule inhibitors have been essential tools for unraveling PARP function, and
      recently the first PARP inhibitors have been approved for the treatment of
      various human cancers. However, inhibitors have only been developed for a few
      PARPs and in vitro profiling has revealed that many of these exhibit
      polypharmacology across the PARP family. In this review, we discuss the history,
      development, and current state of the field, highlighting the limitations and
      opportunities for PARP inhibitor development.

PMID- 30242510
TI  - Ischiocrural Strength May Be a Better Prognostic Marker Than Quadriceps Strength
      in COPD.
AB  - It is well known that chronic obstructive pulmonary disease (COPD) patients
      present with muscle dysfunction that may not correlate with the degree of
      severity of airflow obstruction. Historically, the strength deficit of the knee
      extensor musculature (quadriceps) has been described as an independent factor of
      mortality in COPD. We present the results of a retrospective study with
      longitudinal follow-up of 60 patients with severe COPD followed for 7 years.
      During follow-up 22 patients died, mainly of respiratory cause. We have observed
      that the strength of knee flexor muscles (ischiocrural) and dominant handgrip
      were independent predictors of mortality in severe COPD patients. However, knee
      extensor strength (quadriceps) was not an independent predictor of mortality.
      This is the first study which highlights the importance of knee flexor
      musculature as a prognostic factor in COPD.

PMID- 30242512
TI  - Extracellular Vesicles in Fungi: Composition and Functions.
AB  - The comprehension of fungal biology is important for several reasons. Besides
      being used in biotechnological processes and in the food industry, fungi are also
      important animal and vegetal pathogens. Fungal diseases in humans have a great
      importance worldwide, and understanding fungal biology is crucial for treatment
      and prevention of these diseases, especially because of emerging antifungal
      resistance that poses great epidemiological risks. Communication through
      extracellular vesicles is a ubiquitous mechanism of molecule transfer between
      cells and is used to transport proteins, nucleic acids, lipids, and other
      biologically active molecules. Several pathogens can produce and transfer
      extracellular vesicles, and the importance of this pathway in fungal
      communication with hosts and between fungal cells has been described for several
      species in the last years, as shown for Saccharomyces cereviseae, Cryptococcus
      neoformans, Candida albicans, Paracoccidioides braziliensis, Sporothrix
      schenckii, Candida parapsilosis, Malassezia sympodialis, Histoplasma capsulatum,
      among others. In this chapter, we review the role of extracellular vesicles in
      fungal communication, interaction with hosts and with the environment, and also
      highlighting important molecules found in fungal EVs.

PMID- 30242513
TI  - Opportunities for Lipid-Based Probes in the Field of Immunology.
AB  - Lipids perform a wide range of functions inside the cell, ranging from structural
      building block of membranes and energy storage to cell signaling. The mode of
      action of many signaling lipids has remained elusive due to their low abundance,
      high lipophilicity, and inherent instability. Various chemical biology
      approaches, such as photoaffinity or activity-based protein profiling methods,
      have been employed to shed light on the biological role of lipids and the lipid
      protein interaction profile. In this review, we will summarize the recent
      developments in the field of chemical probes to study lipid biology, especially
      in immunology, and indicate potential avenues for future research.

PMID- 30242514
TI  - Safety range for acute limb lengthening in primary total hip arthroplasty.
AB  - PURPOSE: There is no documented maximum amount that an extremity can be safely
      lengthened in primary total hip arthroplasty (THA) without neurologic or soft
      tissue complications. We retrospectively reviewed patients who underwent primary
      THA with acute limb lengthening and investigated the safety range for acute limb
      lengthening in primary THA. METHODS: This study included 61 hips in 52 patients
      who underwent primary THA with acute limb lengthening (more than 2.5 cm) without
      femoral shortening osteotomy. The amount of lengthening was measured from pre
      operative and post-operative X-ray films using computer graphics software, then
      the ratios of the amount of lengthening to femoral length (L/F ratio = amount of
      lengthening / femoral shaft length * 100) were calculated. We investigated
      correlation with nerve and soft tissue complications at operation in regard to
      this index. RESULTS: The average amount of lengthening was 3.0 cm (2.5 to 4.8).
      The average L/F ratio was 7.9 (6.2 to 12.9). There were seven nerve complications
      and two soft tissue complications in the whole series. In all nine complications,
      eight indicated higher L/F ratios than 8.7. Altogether, 12 hips indicated a
      higher L/F ratio than 8.7; 66% of them showed neurological or soft tissue
      problems. ROC curve analysis indicated that the optimal cutoff value of the L/F
      ratio was 8.7, which predicted acute lengthening-related complications with a
      sensitivity of 88.9% and a specificity of 92.3% (AUC = 0.88). CONCLUSION: The
      patients who underwent THA with acute lengthening of more than 8.7% of femoral
      shaft length are at high risk of complications caused by acute limb lengthening
      in primary THA.

PMID- 30242515
TI  - Correction to: Denosumab does not decrease the risk of lung metastases from bone
      giant cell tumour.
AB  - Last and second name of an author have been mixed up. It shows Piergiuseppe as
      the last name, but his second name is Tanzi and the first name is Piergiuseppe.

PMID- 30242516
TI  - Pelvic pitch and roll during total hip arthroplasty performed through a
      posterolateral approach. A potential source of error in free-hand cup
      positioning.
AB  - PURPOSE: Intraoperative pelvic motion can alter the perceived cup inclination and
      version during non-navigated THA. We quantified pelvic motion during different
      phases of primary THA performed in the lateral decubitus through a posterolateral
      approach. METHODS: Pelvic roll (rotation of the coronal plane) and pitch angles
      (rotation parallel to the coronal plane) were studied in 75 patients undergoing
      THA for osteoarthritis by four arthroplasty surgeons. Ten steps of surgery were
      defined. Angular motion was recorded with a miniature surgical device that
      utilizes inertial sensors. RESULTS: The mean absolute roll ranged from 0.03
      degrees  detected at the end of surgery to 4.13 degrees  detected during
      acetabular exposure. The mean absolute pitch ranged from 0.05 degrees  detected
      at the end of surgery to 2.54 degrees  detected during hip dislocation. The
      maximum pelvic roll and pitch detected during surgery averaged 17.62 degrees 
      (SD: 5.08) and 9.3 degrees  (SD: 3.39) respectively. Absolute roll and pitch
      angles were not affected by patient's BMI, sex, pre-operative hip motion, or
      surgeon. Before cup insertion, the greatest mean change in roll was observed
      during acetabular exposure (10.02 degrees  anteriorly), and for pitch was
      observed during dislocation (1.88 degrees  caudally). CONCLUSION: During THA
      performed through a posterolateral approach, there is a progressive anterior
      pelvic roll that peaks before cup insertion. This can lead to underestimation of
      cup anteversion during non-navigated THA. The anterior roll does not completely
      correct, even when all retractors and external forces acting on the pelvis are
      removed. Pelvic pitch that could affect the perceived cup inclination occurs to a
      lesser extent than pelvic roll.

PMID- 30242517
TI  - Using the child behavior checklist to determine associations between psychosocial
      aspects and TMD-related pain in children and adolescents.
AB  - BACKGROUND: Since children and adolescents are frequently experiencing emotional
      and behavioral consequences due to pain, their parents should be aware of this
      emotional and behavioral status. Therefore, the aim of this study was to analyze
      and describe the parents' reports of the emotional and behavioral status of
      children and adolescents with different types of temporomandibular disorders
      using the Child Behavior Checklist. METHODS: This Cross-sectional study comprises
      of 386 randomly selected children and adolescents that ages between 10 and 18
      years in Jeddah. One day prior the clinical examination according to Research
      Diagnostic Criteria for temporomandibular disorders (TMD) Axis I and II, Arabic
      version of the Child Behavior Checklist scale was distributed to the parents of
      participant. According to the diagnosis, the participants were divided into three
      groups; non-TMD group, TMD-pain group, and TMD-painfree group. RESULTS: In regard
      to internalizing problems, the parents to the children and adolescents in the TMD
      pain group rated a higher frequency of anxiety, depression and somatic complaints
      in their children than the parents of children in the non-TMD group (p < 0.05).
      Only one significant association regarding the externalizing problems was found
      for the aggressive behavior in the TMD-pain group. CONCLUSION: The parents rated
      that their children with TMD-pain suffer from emotional, somatic and aggressive
      behavior to a higher degree than healthy control subjects. Also, the parents
      believed that TMD-pain influenced their children's physical activities but not
      social activities.

PMID- 30242518
TI  - High calcium intake in men not women is associated with all-cause mortality risk:
      Melbourne Collaborative Cohort Study.
AB  - : The risk of mortality associated with high dietary calcium is uncertain. Unlike
      a highly publicised study in Swedish women, high dietary calcium intake in men
      not women-was associated with increased all-cause mortality. PURPOSE: The
      association of dietary calcium with mortality is controversial. A study of women
      from the Swedish Mammography Cohort (SMC) suggested higher calcium was associated
      with higher mortality risk, whilst a study of Australian adults from the
      Melbourne Collaborative Cohort Study (MCCS) suggested higher intakes were
      associated with lower mortality risk. Thus, we aimed to perform a sex-specific re
      analysis of the MCCS to evaluate the association of dietary calcium with
      mortality outcomes and directly compare hazard estimates (95% confidence
      intervals) in women with those from the SMC. METHODS: A prospective cohort study
      of community-dwelling Australian adults was conducted, in which 34,627
      individuals (women 20,834 (60.2%); mean +/- SD, age = 54 +/- 8 years) were
      included at baseline after excluding those with prevalent cardiovascular (CV)
      disease, cancer or incomplete data. Energy-adjusted dietary calcium was
      categorised into the following levels of consumption (mg/day): < 600, 600-999,
      1000-1399 and >= 1400. Mortality from all-causes, any cardiovascular disease and
      myocardial infarction was determined. Mortality hazards relative to intakes were
      estimated to be of 600-999 mg/day. RESULTS: In women, hazard estimates for
      calcium intake of >= 1400 mg/day did not reach significance for all-cause (HR =
      0.85; 0.66, 1.10) or CV (HR = 1.10; 0.69, 1.81) mortality in adjusted models. In
      men, intakes of >= 1400 mg/day were associated with a 42% increased all-cause
      mortality risk (HR = 1.42; 1.02, 1.99). There was a trend toward increased CV
      mortality (HR = 1.83; 0.94, 3.55). CONCLUSION: Contrary to findings from a
      similar study conducted in Swedish women, Australian women, after adjustment for
      cofounders showed no increase in mortality risk with high calcium intakes
      possibly reflecting differences in calcium handling dynamics, diet or lifestyle
      factors between the two countries. We identified an increased risk for men.

PMID- 30242519
TI  - Migraine and cluster headache - the common link.
AB  - Although clinically distinguishable, migraine and cluster headache share
      prominent features such as unilateral pain, common pharmacological triggers such
      glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and
      response to triptans and neuromodulation. Recent data also suggest efficacy of
      anti CGRP monoclonal antibodies in both migraine and cluster headache. While
      exact mechanisms behind both disorders remain to be fully understood, the
      trigeminovascular system represents one possible common pathophysiological
      pathway and network of both disorders. Here, we review past and current
      literature shedding light on similarities and differences in phenotype,
      heritability, pathophysiology, imaging findings and treatment options of migraine
      and cluster headache. A continued focus on their shared pathophysiological
      pathways may be important in paving future treatment avenues that could benefit
      both migraine and cluster headache patients.

PMID- 30242520
TI  - Fabrication of Efficient Organic-Inorganic Perovskite Solar Cells in Ambient Air.
AB  - Although many groups have been trying to prepare perovskite solar cells (PSCs) in
      ambient air, the power conversion efficiency (PCE) is still low. Besides, the
      effect of moisture on the formation of perovskite films is still controversial.
      In this paper, we studied the effect of moisture on the formation of perovskite
      films in detail, and found that moisture can speed up the crystallizing process
      of PbI2 films to form poor-quality films with large grain size and surface
      roughness, while, for the conversion of PbI2 to perovskite films, a small amount
      of moisture is not adverse, and even beneficial. On this basis, we report the
      successful fabrication of efficient mesoporous PSCs with PCE of 16.00% under
      ambient air conditions at 25% relative humidity by adding a small amount of n
      butyl amine into the solution of PbI2 to enhance the quality of PbI2 films and
      thus to achieve high-quality perovskite films with smooth surface, large crystal
      grains, and high crystal quality.

PMID- 30242521
TI  - Sex Differences in the Management of Advanced Heart Failure.
AB  - PURPOSE OF REVIEW: Heart failure (HF) is prevalent among women and remains a
      leading cause of morbidity and mortality in the United States. Currently, 3
      million women live with HF and the prevalence is projected to continue to
      increase. The purpose of this review is to highlight sex differences in the use
      and response to evidence-based pharmacological, device, and advanced HF
      therapies, as well as explore emerging areas of research in sex differences in
      the treatment of HF. RECENT FINDINGS: Under-representation of women in clinical
      HF trials has limited our understanding of sex-related differences in the
      treatment and outcomes of HF. Important sex differences exist in the use of
      evidence-based HF therapies and clinical response among women with HF. In
      general, women tend to obtain the same clinical benefit from evidence-based HF
      drug and device therapies, but the utilization rates of guideline-directed
      medical therapies remain poor compared to men. Future research efforts should
      focus on increasing the enrollment of women in HF trials to help gain helpful
      insight into sex-specific differences in treatment effects and subsequent
      clinical outcomes.

PMID- 30242522
TI  - Leveraging EUnetHTA's conceptual framework to compare HTA decision drivers in
      France, Italy, and Germany from a manufacturer's point of view.
AB  - BACKGROUND: Health Technology Assessments (HTA) procedures differ substantially
      across the various European countries. We reviewed recent appraisals of a
      pharmaceutical manufacturer in three major European markets (France; Italy;
      Germany) and identified and categorized related decision drivers. METHODS: New
      marketing authorisation between January 2011 and August 2017, and Roche being the
      Marketing Authorization Holder, were included. Outcome of HTA appraisals by the
      Haute Autorite de Sante (HAS), Agenzia Italiana del Farmaco (AIFA), and Federal
      Joint Committee (Gemeinsamer Bundesausschuss, G-BA) were reviewed. Respective
      decision drivers were identified and commonalities and differences across the
      three countries were determined leveraging the EUnetHTA conceptual taxonomy (i.e.
      the 9 domains of the EUnetHTA core model). RESULTS: Within that time period Roche
      received European marketing authorization for eight new molecular entities (10
      indications, respectively). Outcome of HTA appraisals was heterogeneous across
      the three countries. However, the four clinical domains of the EUnetHTA core
      model were driving the national HTA appraisals, with the clinical effectiveness
      domain being of most importance. Important drivers related to the other three
      clinical domains included the target patient population (subgroups, Germany), the
      current management of the condition (unmet need, Italy), the regulatory status
      (Orphan Designation, Germany), as well as safety considerations (all three
      countries). Average time between EMA approval and full commercial availability of
      new medicines was 63 (Germany), 459 (Italy), and 557 days (France). CONCLUSIONS:
      The clinical domains of the EUnetHTA framework are mainly driven by national HTA
      appraisals, providing a suitable starting point for further developing a joint
      European view on value and evidence. Underlying topics and issues still reveal
      considerable differences.

PMID- 30242524
TI  - Enhanced Visible Light-Responsive Photocatalytic Properties of Ag/BiPbO2Cl
      Nanosheet Composites.
AB  - Ag/BiPbO2Cl nanosheet composites were successfully prepared by hydrothermal
      synthesis and photo-reduction. The morphology, microstructure, and optical
      properties of the as-prepared Ag/BiPbO2Cl nanosheet composites were characterized
      using TEM, XRD, and UV-Vis diffuse reflection spectroscopy. The prepared
      Ag/BiPbO2Cl nanosheet composites with 0.5 wt% Ag exhibit favorable photocatalytic
      activity, which is 3.6 times that of BiPbO2Cl nanosheet. The enhanced
      photocatalytic properties can be attributed to the inner electromagnetic field,
      higher visible light response range, excellent conductivity, and lower Fermi
      level of Ag.

PMID- 30242523
TI  - Conversion of Multi-layered MoTe2 Transistor Between P-Type and N-Type and Their
      Use in Inverter.
AB  - Both p-type and n-type MoTe2 transistors are needed to fabricate complementary
      electronic and optoelectronic devices. In this study, we fabricate air-stable p
      type multi-layered MoTe2 transistors using Au as electrode and achieve the
      conversion of p-type transistor to n-type by annealing it in vacuum. Temperature
      dependent in situ measurements assisted by the results given by first-principle
      simulations indicate that n-type conductance is an intrinsic property, which is
      attributed to tellurium vacancies in MoTe2, while the device in air experiences a
      charge transfer which is caused by oxygen/water redox couple and is converted to
      air-stable p-type transistor. Based on p-type and n-type multi-layered MoTe2
      transistors, we demonstrate a complementary inverter with gain values as high as
      9 at VDD = 5 V.

PMID- 30242526
TI  - Carbon dots prepared from Litchi chinensis and modified with manganese dioxide
      nanosheets for use in a competitive fluorometric immunoassay for aflatoxin B1.
AB  - An enzyme-linked immunoassay is described for the fluorometric determination of
      aflatoxin B1 (AFB1). It is based on the use of carbon dots (CDs) synthesized by
      using Litchi chinensis as the carbon source via a hydrothermal method. The CDs
      were modified with MnO2 nanosheets upon which their blue fluorescence (with
      excitation/emission peaks at 340/425 nm) is quenched. In the presence of AFB1, a
      competitive immunoreaction takes place between (1) AFB1 conjugated to bovine
      serum albumin and deposited in the wells of a microplate, and (2) antibody
      against AFB1 and labeled with alkaline phosphatase (ALP). On subsequent addition
      of ascorbic acid 2-phosphate, it will be hydrolyzed by ALP to form ascorbic acid
      and phosphate. The ascorbic acid produced reduces MnO2 nanosheets to Mn2+ ions
      which then are relased from the CDs. This causes the recovery of fluorescence.
      Under optimum conditions, fluorescence decreases linearly with increasing AFB1
      concentration in the range from 1.0 ng.kg-1 to 10 MUg.kg-1, and the limit of
      detection is 0.69 ng.kg-1. The precision of this method (expressed as RSD) is +/
      10.3%. The accuracy was tested by analyzing both naturally contaminated and
      spiked food samples, and the results were in good agreement with those obtained
      by the established ELISA. Graphical abstract Enzyme hydrolysate-triggered redox
      reaction of carbon dot-functionalized MnO2 nanosheets was developed for the
      fluorescence immunoassay of aflatoxin B1 in foodstuff.

PMID- 30242527
TI  - A multi-criterion approach for prioritizing areas in urban ecosystems for active
      restoration following invasive plant control.
AB  - Resources for biodiversity conservation and invasive plant management are
      limited, and restoring invaded vegetation is labour-intensive and expensive.
      Managers must prioritize their actions to achieve their goals efficiently and
      effectively. They must distinguish between areas that require only the removal of
      invasive alien plants ("passive restoration") from those that require additional
      restoration measures ("active restoration"). This study used a multi-criterion
      approach (Analytical Hierarchical Process) to develop a framework for identifying
      areas that require active restoration, and then to prioritize these areas for
      active restoration. The South African city of Cape Town is used as a test case to
      illustrate the utility of the framework. Framework criteria selected in
      determining the need for active restoration included: dominant alien species
      invading the area, density of invasion, duration of invasion, indigenous
      vegetation cover, adjacent land use, level of disturbance, size of the area,
      aspect, soil texture, soil depth and erodibility, slope and vegetation type. In
      deciding which areas to prioritize for active restoration, factors such as
      vegetation conservation status, selection in a regional conservation plan and
      connectivity function were assessed. Importance in ecosystem functioning (by
      providing a diversity of habitats and soil conservation) and the delivery of
      ecosystem service benefits were also considered. The resulting framework provides
      an objective tool for prioritizing sites for active restoration.

PMID- 30242525
TI  - Enantiomer discrimination in beta-phenylalanine degradation by a newly isolated
      Paraburkholderia strain BS115 and type strain PsJN.
AB  - Despite their key role in numerous natural compounds, beta-amino acids have
      rarely been studied as substrates for microbial degradation. Fermentation of the
      newly isolated Paraburkholderia strain BS115 and the type strain P. phytofirmans
      PsJN with beta-phenylalanine (beta-PA) as sole nitrogen source revealed (S)
      selective transamination of beta-PA to the corresponding beta-keto acid by both
      strains, accompanied by substantial formation of acetophenone (AP) from
      spontaneous decarboxylation of the emerging beta-keto acid. While the PsJN
      culture became stationary after entire (S)-beta-PA consumption, BS115 showed
      further growth at a considerably slower rate, consuming (R)-beta-PA without
      generation of AP which points to a different degradation mechanism for this
      enantiomer. This is the first report on degradation of both enantiomers of any
      beta-amino acid by one single bacterial strain.

PMID- 30242528
TI  - Perceptions of Government and Research Expert Groups and Their Implications for
      Watershed Management in Oklahoma, USA.
AB  - The collaborative approach for sustainable management of watersheds is built on
      engagement of diverse stakeholders. Climate variability and anthropogenic
      activities increasingly impose challenges to successful management, as do
      contrasts in stakeholder perceptions about those processes. To assess differences
      in perceptions about watershed issues, we conducted a focus group meeting of
      expert stakeholder groups from research institutions, and state and federal
      agencies in the management of Cimarron River Watershed, Oklahoma. We employed the
      Strengths, Weaknesses, Opportunities, and Threats (SWOTs) approach to identify
      important issues, and the analytic hierarchy process to rank the perceptions of
      these groups. We found incongruity between these two groups over internal factors
      (SW) and external factors (OT) risking sustainable watershed management. External
      threats such as climate change dominated the research group perceptions, whereas
      internally prevalent weaknesses such as inability to track water use and lack of
      a common platform to share scientific data, dominated the government group
      perceptions. Despite these differences, both groups identified the negative
      aspect (W + T) as dominant over the positive aspect (S + O), which suggests a
      pessimistic watershed management future, with risks prevailing over the
      opportunities. We see this particular congruity of these two stakeholders as an
      opportunity to initiate a collaborative approach to watershed management in
      Oklahoma. We also note that the most important factor from each group corresponds
      to a relatively modest importance from the other group, and therefore suggests
      the possibility of cooperation rather than conflict in management goals should
      collaborative watershed management become established in the watershed.

PMID- 30242529
TI  - Assessment of Water Resources Sustainability in Mainland China in Terms of Water
      Intensity and Efficiency.
AB  - Investigation into water resources sustainability (WRS) is vital for a regional
      sustainable development strategy. This paper aimed to quantitatively evaluate the
      WRS in mainland China using a three-layer indicator system. Three important
      factors significantly affecting WRS are: water resources quantity (WRQ), water
      intensity (WI) and water efficiency (WE). Assessment of the three indicators was
      carried out in 356 cities where each indicator was graded from "very low" to
      "very high" according to the value magnitude. China was then classified into four
      zones to differentiate regional variations of the impact of water intensity and
      efficiency on sustainability. Results showed that 34% of the areas had "medium"
      to "high" WI indicator values and 58% of the areas had "low" to "very low" WE
      indicator values. The indicator values of WI were ordered as Zone I > Zone II >
      Zone III > Zone IV; whereas the WRS were ordered as: Zone I < Zone II < Zone III
      < Zone IV. It is recommended that water resource policies be turned to a more
      sustainable management strategy in areas with high WI and low WE. Zone I regions
      should be focused on particularly with limited resources and extreme
      exploitation. The results provide a valuable basis for macro-level decision
      making concerned with regional sustainable development strategy for the entire
      mainland China.

PMID- 30242530
TI  - [Long-term opioid therapy of non-cancer pain : Prevalence and predictors of
      hospitalization in the event of possible misuse].
AB  - BACKGROUND: One major concern of long-term opioid therapy (LTOT) for chronic
      noncancer pain (CNCP) is the risk of abuse of prescribed opioids. OBJECTIVE: To
      examine the prevalence and predictors of opioid use-related hospitalizations and
      potential abuse of prescribed opioids by persons with LTOT for CNCP in a sample
      representative of the German statutory health insurance companies. METHODS:
      Retrospective cross-sectional study in 2014. Anonymized German health claims
      database, including 4,028,618 insured individuals of 69 German statutory health
      insurances. Univariate logistic regression models to evaluate demographic and
      medical characteristics associated with hospital stays and a diagnosis of mental
      and behavioral disorders due to alcohol, opioids, tranquilizers, multiple
      substances and intoxications by narcotic agents in insured individuals with CNCP
      receiving LTOT. RESULTS: The prevalence of LTOT for CNCP was 0.8%; 9.9% of these
      insured individuals received high-dose LTOT (>=120 morphine equivalent mg/day).
      The 1-year prevalence of hospital stays with a diagnosis of mental and behavioral
      disorders due to alcohol, opioids, tranquilizers, multiple substances and
      intoxications by narcotic agents was 1.75% of persons with LTOT. These diagnoses
      were strongly associated with prescriptions of tranquilizers (odds ratio [OR]
      3.63; 95% confidence interval [CI] 3.03; 4.36) and moderately associated with
      diagnosis of depression (OR 2.52; 95% CI 2.12; 3.00) and slightly associated with
      diagnosis of somatoform pain disorder (OR 1.89; 95% CI 1.56; 2.28) and high-dose
      LTOT (OR 1.81; 95% CI 1.44; 2.27). DISCUSSION: The study is in line with the
      recommendations of the German national guidelines on long-term opioid therapy of
      chronic non-cancer pain (LONTS) to avoid concomitant prescription of
      tranquilizers for CNCP and to carefully select and monitor patients with
      depression and somatoform pain disorder.

PMID- 30242531
TI  - Intersectional Identities and HIV: Race and Ethnicity Drive Patterns of Sexual
      Mixing.
AB  - Large disparities exist in HIV across racial and ethnic populations-with Black
      and Latino populations disproportionately affected. This study utilizes a large
      cohort of young men who have sex with men (YMSM) to examine how race and
      ethnicity drive sexual partner selection, and how those with intersecting
      identities (Latinos who identify as White or Black) differ from Latinos without a
      specific racial identification (Latinos who identify as "Other"). Data come from
      YMSM (N = 895) who reported on sexual partners (N = 3244). Sexual mixing patterns
      differed substantially by race and ethnicity. Latinos who self-identified as
      "Black" reported mainly Black partners, those who self-identified as "White"
      predominantly partnered with Whites, while those who self-identified as "Other"
      mainly partnered with Latinos. Results suggested that Black-Latino YMSM are an
      important population for prevention, as their HIV prevalence neared that of Black
      YMSM, and their patterns of sexual partnership suggested that they may bridge
      Black YMSM and Other-Latino YMSM populations.

PMID- 30242532
TI  - Effects of Tendon Degeneration on Predictions of Supraspinatus Tear Propagation.
AB  - Rotator cuff tendons undergo degeneration with age, which could have an impact on
      tear propagation. The objective of this study was to predict tear propagation for
      different levels of tissue degeneration using an experimentally validated finite
      element model of a supraspinatus tendon. It was hypothesized that greater amounts
      of degeneration will result in tear propagation at lower loads than tendons with
      less degeneration. Using a previously-validated computational model of
      supraspinatus tendon, 1-cm tears were introduced in the anterior, middle, and
      posterior thirds of the tendon. Cohesive elements were assigned subject-specific
      failure properties to model tear propagation, and tendon degeneration ranging
      from "minimal" to "severe" was modeled by modifying its mechanical properties.
      Tears in tendons with severe degeneration required the smallest loads to
      propagate (122-207 N). Posterior tears required greater loads compared to middle
      and anterior tears at all levels of degeneration. Stress and strain required for
      tear propagation decreased substantially with degeneration, ranging from 8.5 MPa
      and 32.6% strain for minimal degeneration and 0.6 MPa and 4.5% strain for severe
      degeneration. Overall, this work indicates that greater amounts of tendon
      degeneration lead to greater risk of tear propagation, supporting the need for
      early detection and treatment of rotator cuff tears.

PMID- 30242533
TI  - Social style and resilience of macaques' networks, a theoretical investigation.
AB  - Group-living animals rely on efficient transmission of information for optimal
      exploitation of their habitat. How efficient and resilient a network is depend on
      its structure, which is a consequence of the social interactions of the
      individuals that comprise the network. In macaques, network structure differs
      according to dominance style. Networks of intolerant species are more modular,
      more centralized, and less connected than those of tolerant ones. Given these
      structural differences, networks of intolerant species are potentially more
      vulnerable to fragmentation and decreased information transmission when central
      individuals disappear. Here we studied network resilience and efficiency in
      artificial societies of macaques. The networks were produced with an individual
      based model that has been shown to reproduce the structural features of networks
      of tolerant and intolerant macaques. To study network resilience, we deleted
      either central individuals or individuals at random and studied the effects of
      these deletions on network cohesiveness and efficiency. The deletion of central
      individuals had more negative effects than random deletions from the networks of
      both tolerant and intolerant artificial societies. Central individuals thus
      appeared to aid in the maintenance of network cohesiveness and efficiency.
      Further, the networks of both intolerant and tolerant societies appeared to be
      robust to the loss of individuals, as network fragmentation was never observed.
      Our results suggest that despite differences in network structure, networks of
      tolerant and intolerant macaques may be equally resilient.

PMID- 30242534
TI  - Robotics, artificial intelligence and distributed ledgers in surgery: data is
      key!

PMID- 30242535
TI  - Genome-wide analysis of the MYB-CC gene family of maize.
AB  - The MYB-CC gene family encode proteins that harbor a combination of
      characteristic myeloblastosis (MYB) and coiled-coil (CC) domain structures. Some
      MYB-CC genes have been demonstrated to represent transcription factors regulating
      phosphate uptake and controlling the starvation response in plants. Despite their
      physiological importance, a systematic analysis of MYB-CC genes has not been
      reported in maize. In our study, we identified and characterized maize MYB-CC
      genes at whole-genome level. A total of 12 maize MYB-CC genes (ZmMYB-CC1 to ZmMYB
      CC12) were identified located in six out of the 10 chromosomes of maize. Their
      gene structures showed similar splicing patterns and large variations of intron
      length. Multiple sequence alignments revealed that all MYB-CC proteins in maize
      shared conserved sequence cores corresponding to the MYB and CC domains,
      respectively. The family expanded in maize partly due to tandem and segmental
      duplication events. Phylogenetic analysis of MYB-CC genes indicated that the MYB
      CC gene family can be divided into two subfamilies and that gene members with
      same functions were found in the same groups. Results provide a very useful
      reference for cloning and functional analysis of PHR-like genes in maize and
      suggest a method to predict and select appropriate candidate genes for functional
      genomic analysis of useful traits in crop plants.

PMID- 30242536
TI  - Genetic structure of Japanese sea cucumbers (Apostichopus japonicus) along the
      Sanriku coast supports the effect of earthquakes and related tsunamis.
AB  - The Japanese common sea cucumber (Apostichopus japonicus) is a major marine
      product from Sanriku, Japan, but its populations were severely affected by the
      2011 Tohoku earthquake, possibly decreasing its genetic diversity and increasing
      its extinction risk. In this study, we estimated the genetic structure and
      diversity of sea cucumbers from Touni and Yamada Bays of Sanriku over 4 years
      after the earthquake. The between-population genetic structure was estimated
      using two mitochondrial DNA regions (cytochrome c oxidase subunit I and 16S
      rDNA). Genetic differentiation (as measured by pairwise FST) was not significant
      between locations. Thus, even after the tsunami, gene flow and genetic diversity
      among the two sea cucumber populations were maintained. Our data also suggested
      that sea cucumbers in Sanriku experienced population expansion of about 0.20-0.24
      million years ago, during the stable Mindel-Riss interglacial period. We conclude
      that A. japonicus populations in Sanriku could maintain their genetic structure
      throughout multiple disastrous tsunamis over the past several 1000 years. The
      high dispersal ability of planktonic larvae may enable the entrance of new
      recruits, thereby reducing risks associated with genetic structure and diversity
      changes stemming from mass die-offs in a given body of water from the past to the
      present.

PMID- 30242537
TI  - Health, Science, Faith, and Stewardship.

PMID- 30242539
TI  - Gestational trophoblastic neoplasia with brain metastasis at initial
      presentation: a retrospective study.
AB  - OBJECTIVE: To evaluate the survival and functional outcome of patients with brain
      metastasis due to gestational trophoblastic neoplasia (GTN). METHODS: A 17-year
      retrospective study based on case review of women with brain metastasis from GTN
      identified by the electronic databases held in the French Reference Centre.
      PRIMARY OUTCOME MEASURE: 5-year overall survival calculated with the Kaplan-Meier
      method. SECONDARY OUTCOME MEASURES: causes of death, prognostic factors and
      functional outcomes. RESULTS: 21 patients had GTN brain metastasis and were
      treated with multidrug chemotherapy without concomitant whole-brain radiation
      therapy. Three patients died early (< 4 weeks) of cerebral hemorrhage, 3 died >=
      1 months after treatment initiation and 15 were alive at the date of last
      contact. The overall survival rate at 5 years was 69.8% (95% CI 44.3-85.3). After
      excluding early deaths, the survival rate at 5 years was 81.5% (95% CI 52.3
      93.7). No predictive factor of survival was identified. Although 11 of the 12
      (92%) surviving patients contacted still reported sequelae, nine of them (75%)
      had resumed a normal life. CONCLUSIONS: After excluding early deaths, this study
      implies a high survival rate in patients with brain metastasis from GTN. These
      results were achieved in the total absence of whole-brain radiotherapy and almost
      completely without the need for intrathecal methotrexate.

PMID- 30242540
TI  - Interdependence between the aerobic degradation of BPA and readily biodegradable
      substrates by activated sludge in semi-continuous reactors.
AB  - The objective of the present work was to analyze the interrelationship between
      the aerobic degradation of BPA and readily biodegradable substrates by activated
      sludge (AS) in semi-continuous reactors (SCRs). AS were obtained from three SCRs
      fed with glucose, acetate or peptone. AS from these reactors were used as inocula
      for three SCRs that were fed with each biogenic substrate, and for three SCRs
      that were fed with the biogenic substrate and BPA. In all cases, dissolved
      organic carbon (DOC), BPA, total suspended solids (TSS) and respirometric
      measurements were performed. Although BPA could be removed in the presence of all
      the tested substrates, AS grown on acetate exhibited the longest acclimation to
      BPA. Reactors fed with peptone attained the lowest TSS concentration; however,
      these AS had the highest specific BPA degradation rate. Specific DOC removal
      rates and respirometric measurements demonstrated that the presence of BPA had a
      negligible effect on the removal of the tested substrates. A mathematical model
      was developed to represent the evolution of TSS and DOC in the SCRs as a function
      of the operation cycle. Results suggest that the main effect of BPA on AS was to
      increase the generation of microbial soluble products. This work helps to
      understand the relationship between the biodegradation of BPA and readily
      biodegradable substrates.

PMID- 30242538
TI  - Using Bloodmeal Analysis to Assess Disease Risk to Wildlife at the New Northern
      Limit of a Mosquito Species.
AB  - The historically southeastern mosquito species Culex erraticus has over the last
      30 years undergone a marked expansion north. We evaluated this species' potential
      to participate in local disease cycles in the northeastern USA by identifying the
      vertebrate sources of blood in Cx. erraticus specimens from New Jersey. We found
      that the majority of bloodmeals (92.6%) were derived from birds, followed by 6.8%
      from mammals (of which half were human), and a single amphibian bloodmeal from a
      spring peeper (0.56%). Medium- and large-sized water birds from the order
      Pelecaniformes made up 60.4% of the bird species and 55.9% of all identified
      hosts. This group of birds is known enzootic hosts of arboviruses such as eastern
      equine encephalitis virus, for which Cx. erraticus is a competent vector.
      Additionally, we screened blooded mosquitoes for avian malaria parasites and
      identified three different lineages of Plasmodium, including what may represent a
      new Plasmodium species (likely a wetland bird specialist) in bloodmeals from
      Green Herons, a Great Egret, and a Double-Crested Cormorant. Our results support
      the utility of mosquito bloodmeals as sources of information about circulating
      wildlife pathogens and reveal the potential of range-expanding species to
      intensify local zoonoses and bridge enzootic pathogens to humans.

PMID- 30242541
TI  - Assessing the predictability of self-harm in a high-risk adult prisoner
      population: a prospective cohort study.
AB  - BACKGROUND: Prisoners are at increased risk of self-harm and when either intent
      is expressed, or an act of self-harm carried out, prisoners in the UK are subject
      to self-harm/suicide monitoring (referred to as "open ACCT" monitoring). However,
      there is a paucity of validated instruments to identify risk of self-harm in
      prisoner populations. In response to the need to support prison staff to
      determine who is at increased risk of self-harm or repeat self-harm, the aim of
      this study was to determine whether any pre-existing, standardised instruments
      could usefully identify future self-harm events in prisoners undergoing ACCT
      monitoring. METHODS: A multi-stage prospective cohort study was conducted, where
      the Prison Screening Questionnaire (PriSnQuest), a modified Borderline Symptom
      List-23 (BSL-23), Self-Harm Inventory (SHI), Patient Health Questionnaire-9 (PHQ
      9) and Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM)
      instruments were administered to prisoners aged 18 and above, who were judged to
      be at an increased risk of self-harm (on open ACCT monitoring) during the
      recruitment phase. A 6-month follow-up determined self-harm occurrence since
      baseline, and Area-Under-the-Curve (AUC) analysis examined the ability of the
      instruments to predict future self-harm. RESULTS: Prison records established that
      29.1% self-harmed during the follow up period, involving a total of 423 self-harm
      events reported from 126 individuals, followed up for 66,789 prisoner days
      (median 167 days; IQR 71-207.5 days). This translated to an 'event incidence' of
      6.33 per 1000 prisoner days of those who had been placed upon an ACCT, or
      'prisoner incidence' of 1.89 per 1000 days, with considerable variation for both
      gender and participating prisons. None of the summary scores derived from the
      selected instruments showed a meaningful ability to predict self-harm, however,
      exploratory logistic regression analysis of individual background and instrument
      items revealed gender-specific item sets which were statistically significant in
      predicting future self-harm. CONCLUSIONS: Prospective self-harm was not predicted
      by any of the pre-existing instruments that were under consideration. Exploratory
      logistic regression analysis did reveal gender-specific item sets, producing
      predictive algorithms which were statistically significant in predicting future
      self-harm; however, the operational functionality of these item sets may be
      limited.

PMID- 30242542
TI  - miR-410-3p Suppresses Cytokine Release from Fibroblast-Like Synoviocytes by
      Regulating NF-kappaB Signaling in Rheumatoid Arthritis.
AB  - miR-410-3p acts as an oncogene or a tumor suppressor in some malignancies.
      However, its role in rheumatoid arthritis (RA) is unknown. The study was
      conducted to investigate the effect of miR-410-3p on the pathogenesis of RA. Real
      time RT-PCR was used to determine the mRNA levels of miR-410-3p in synovial
      tissues and fibroblast-like synoviocytes (FLSs). An ELISA was performed to
      examine the production levels of tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-1beta, IL-6, and matrix metalloproteinase (MMP)-9. Western blotting was
      conducted to determine the protein levels of IkappaB-alpha, p-IkappaBalpha, p65,
      and p-p65. Nuclear factor (NF)-kappaB activation and nuclear translocation assays
      were performed to confirm the activation of NF-kappaB. We found that the
      expression level of miR-410-3p was downregulated in synovial tissues and FLSs
      from RA. Overexpression of miR-410-3p significantly reduced the secretion of TNF
      alpha, IL-1beta, IL-6, and MMP-9 in human RA fibroblast-like synoviocytes (HFLS
      RA); whereas miR-410-3p inhibition increased the expression levels of these
      cytokines. Furthermore, miR-410-3p suppresses the activation of NF-kappaB
      signaling pathway. Moreover, NF-kappaB inhibitor restored the elevation of TNF
      alpha, IL-1beta, IL-6, and MMP-9 induced by miR-410-3p inhibition. Our results
      demonstrate that miR-410-3p acts an inflammatory suppressor in the pathogenesis
      of RA by regulating the NF-kappaB signaling pathway. These data suggest a novel
      function of miR-410-3p and provide insight into the complex mechanisms involved
      in RA.

PMID- 30242544
TI  - Optimizing cancer pain management in resource-limited settings.
AB  - PURPOSE: Adequate cancer pain management (CPM) is challenging in resource-limited
      settings, where current international guideline recommendations are difficult to
      implement owing to constraints such as inadequate availability and accessibility
      of opioids, limited awareness of appropriate opioid use among patients and
      clinicians, and lack of guidance on how to translate the best evidence into
      clinical practice. The multinational and multidisciplinary CAncer Pain managEment
      in Resource-limited settings (CAPER) Working Group proposes a two-step initiative
      to bridge clinical practice gaps in CPM in resource-limited settings. METHODS: A
      thorough review of the literature, a steering committee meeting in February 2017,
      and post-meeting teleconference discussions contributed to the development of
      this initiative. As a first step, we developed practical evidence-based CPM
      algorithms to support healthcare providers (HCPs) in tailoring treatment
      according to availability of and access to resources. The second part of the
      initiative proposes a framework to support an effective implementation of the CPM
      algorithms that includes an educational program, a pilot implementation, and an
      advocacy plan. RESULTS: We developed CPM algorithms for first-line use,
      breakthrough cancer pain, opioid rotation, and refractory cancer pain based on
      the National Comprehensive Cancer Network guidelines and expert consensus. Our
      proposed educational program emphasizes the practical elements and illustrates
      how HCPs can provide optimal CPM according to evidence-based guidelines despite
      varied resource limitations. Pilot studies are proposed to demonstrate the
      effectiveness of the algorithms and the educational program, as well as for
      providing evidence to support a draft advocacy document, to lobby policymakers to
      improve availability and accessibility of analgesics in resource-limited
      settings. CONCLUSIONS: These practical evidence-informed algorithms and the
      implementation framework represent the first multinational step towards achieving
      optimal CPM in resource-limited settings.

PMID- 30242543
TI  - Fecal calprotectin concentrations in cancer patients with Clostridium difficile
      infection.
AB  - Fecal calprotectin (fCPT) has been used as a surrogate marker for assessment of
      intestinal inflammation. We explore the utility of fCPT values as a diagnostic
      aid in cancer patients with suspected Clostridium difficile infection (CDI). A
      total of 232 stool specimens submitted for GeneXpert C. difficile PCR testing
      were included in the study. All specimens were tested for fCPT and toxin/GDH
      antigens. Clinical severity of CDI cases was determined by the IDSA/SHEA
      criteria. Significant differences of median fCPT values between CDI (n = 117,
      Median 183.6 MUg/g) and non-CDI (n = 115, 145.6 MUg/g, p = 0.006) patients were
      seen. In CDI patents, significantly lower fCPT values were found in patients with
      mild to moderate (n = 95, 182.1 MUg/g) than those with severe and severe to
      complicated (n = 22, 218.5 MUg/g, p = 0.014) scores, and among those that were
      toxin positive (n = 24, 200.2 MUg/g) vs. toxin negative (n = 86, 182.8 MUg/g, p =
      0.044). Despite this overall trend, wide variations in fCPT values were found in
      all categories examined. A logistic regression analysis revealed that the fCPT
      values correlated independently with the severity of clinical manifestations (OR
      = 2.021, 95%CI = 1.132-3.608); however, it did not correlate with other clinical
      outcomes. Our study findings show that high fecal calprotectin levels correlate
      with toxin-positive and clinically severe CDI; however, wide variations in
      individual measurements preclude establishment of reliable cut-offs for routine
      diagnostic use in cancer patients.

PMID- 30242545
TI  - What Can Computational Modeling Tell Us about the Diversity of Odor-Capture
      Structures in the Pancrustacea?
AB  - A major transition in the history of the Pancrustacea was the invasion of several
      lineages of these animals onto land. We investigated the functional performance
      of odor-capture organs, antennae with olfactory sensilla arrays, through the use
      of a computational model of advection and diffusion of odorants to olfactory
      sensilla while varying three parameters thought to be important to odor capture
      (Reynolds number, gap-width-to-sensillum-diameter ratio, and angle of the
      sensilla array with respect to oncoming flow). We also performed a sensitivity
      analysis on these parameters using uncertainty quantification to analyze their
      relative contributions to odor-capture performance. The results of this analysis
      indicate that odor capture in water and in air are fundamentally different. Odor
      capture in water and leakiness of the array are highly sensitive to Reynolds
      number and moderately sensitive to angle, whereas odor capture in air is highly
      sensitive to gap widths between sensilla and moderately sensitive to angle.
      Leakiness is not a good predictor of odor capture in air, likely due to the
      relative importance of diffusion to odor transport in air compared to water. We
      also used the sensitivity analysis to make predictions about morphological and
      kinematic diversity in extant groups of aquatic and terrestrial crustaceans.
      Aquatic crustaceans will likely exhibit denser arrays and induce flow within the
      arrays, whereas terrestrial crustaceans will rely on more sparse arrays with
      wider gaps and little-to-no animal-induced currents.

PMID- 30242547
TI  - Editorial to the paper entitled "pharmacotherapy of premature ejaculation: a
      systematic review and network meta-analysis".

PMID- 30242546
TI  - Hemodynamic findings associated with intraoperative appearances of intracranial
      aneurysms.
AB  - Intracranial aneurysms can be classified into thick-walled aneurysms and thin
      walled aneurysms according to their intraoperative appearances; previous
      publications have revealed that different kinds of intraoperative appearances
      were associated with intraoperative rupture and postoperative complications.
      Here, we tried to evaluate the association between hemodynamic features and
      aneurysm wall appearance using computational fluid dynamics (CFD) method. Forty
      one consecutive patients with unruptured middle cerebral artery (MCA) bifurcation
      aneurysms were included in our study. Based on the appearances observed under the
      microscope, aneurysms were classified into two different types: thick-walled and
      thin-walled aneurysms. Preoperative computed tomographic angiography (CTA) was
      used for geometry reconstruction and CFD analysis. Morphological and hemodynamic
      parameters were compared between the two groups. Eighteen aneurysms were
      classified as thick-walled atherosclerotic ones according to their intraoperative
      appearances. Compared with thin-walled aneurysms, aneurysms with atherosclerotic
      changes had larger geometry parameters (aneurysm depth, maximum height, diameter,
      aspect ratio, size ratio), lower wall shear stress (WSS), and larger low WSS area
      ratio (LSAR). Thick-walled aneurysms characterized by atherosclerotic changes are
      associated with low WSS and larger LSAR. CFD may be a useful tool for
      discriminating the intraoperative appearance of cerebral aneurysms.

PMID- 30242548
TI  - Neuroprotective effects of melatonin on erectile dysfunction in streptozotocin
      induced diabetic rats.
AB  - PURPOSE: To explore the neuroprotective effects and its possible mechanisms of
      melatonin (MT) on erectile dysfunction in streptozotocin-induced diabetic rats.
      METHODS: Twenty-eight Sprague-Dawley rats received intraperitoneal injection of
      streptozotocin and 8 weeks later, the determined diabetic rats randomly got
      intraperitoneal injection of phosphate buffer solution (PBS) or MT. Another 12
      normal rats received PBS treatment. Four weeks later, intracavernous pressure,
      mean arterial pressure, pathological changes in penis, and major pelvic ganglion
      (MPG) were measured. Malondialdehyde, superoxide dismutase, p38 and p-p38 levels
      in penis were detected. RESULTS: Diabetic rats showed significant decreases of
      erectile function accompanied with serious neuropathy in dorsal penile nerve
      (DPN) and MPG, meanwhile collagen deposition, oxidative stress, and p-p38 levels
      in penis were elevated. Melatonin treatment partially but significantly improved
      the erectile function, ameliorated neuropathy in DPN and MPG, and decreased
      collagen deposition, oxidative stress, and p-p38 levels in diabetic rats.
      CONCLUSIONS: Melatonin treatment helps improve erectile function and ameliorate
      neuropathy and fibrosis in diabetic rats. These may be associated with reductions
      in oxidative stress, p38MAPK signaling pathway, and neuropathy.

PMID- 30242549
TI  - Thyroid disorders induced by checkpoint inhibitors.
AB  - Immune checkpoint inhibitors are drugs that inhibit the "checkpoint molecules".
      Different types of cancer immune checkpoint inhibitors have been approved
      recently: CTLA-4 monoclonal antibodies (as ipilimumab); anti-PD-1 monoclonal
      antibodies (as pembrolizumab and nivolumab); and anti-PD-L1 monoclonal antibodies
      (as atezolizumab, avelumab, and durmalumab). The increased immune response
      induced by these agents leads to immune-related adverse events (irAEs), that can
      vary from mild to fatal, according to the organ system and severity. Immune
      related endocrine toxicities are thyroid dysfunctions, hypophysitis, adrenal
      insufficiency, and type 1 diabetes mellitus, and are usually irreversible in 50%.
      In particular, hypophysitis is the most frequent anti-CTLA-4-antibodies-related
      irAE, while thyroid abnormalities (as hypothyroidism, thyrotoxicosis, painless
      thyroiditis, or even "thyroid storm") are more frequently associated with anti-PD
      1-antibodies. The combination of anti-CTLA-4-antibodies, with anti-PD-1
      antibodies, is associated with about 30% of irAEs. Clinical signs and symptoms
      vary according to the influenced target organ. Endocrinopathies can often be
      managed by the treating oncologist. However in more severe cases (i.e. in the
      presence of insulin-dependent diabetes, adrenal insufficiency, or disorders of
      gonadal hormones, or severe hyperthyroidism, or hypothyroidism, or long-lasting
      management of hypophysitis) an endocrinological evaluation, and a prompt therapy,
      are needed.

PMID- 30242551
TI  - Changes in treatment and outcomes after creation of a pulmonary embolism response
      team (PERT), a 10-year analysis.
AB  - Multidisciplinary pulmonary embolism response teams (PERTs) are being implemented
      to improve care of patients with life-threatening PE. We sought to determine how
      the creation of PERT affects treatment and outcomes of patients with serious PE.
      A pre- and post-intervention study was performed using an interrupted time series
      design, to compare patients with PE before (2006-2012) and after (2012-2016)
      implementation of PERT at a university hospital. T-tests, Chi square tests and
      logistic regression were used to compare outcomes, and multivariable regression
      were used to adjust for differences in PE severity. Two-sided p-value < 0.05 was
      considered significant. For the interrupted time-series analysis, data was
      divided into mutually exclusive 6-month time periods (11 pre- and 7 post-PERT).
      To examine changes in treatment and outcomes associated with PERT, slopes and
      change points were compared pre- and post-PERT. Two-hundred and twelve pre-PERT
      and 228 post-PERT patients were analyzed. Patient demographics were generally
      similar, though pre-PERT, PE were more likely to be low-risk (37% vs. 19%) while
      post-PERT, PE were more likely to be submassive (32% vs. 49%). More patients
      underwent catheter directed therapy (1% vs. 14%, p = < 0.0001) or any advanced
      therapy (19 [9%] vs. 44 [19%], p = 0.002) post PERT. Interrupted time series
      analysis demonstrated that this increase was sudden and coincident with
      implementation of PERT, and most noticeable among patients with submassive PE.
      There were no differences in major bleeding or mortality pre- and post-PERT.
      While the use of advanced therapies, particularly catheter-directed therapies,
      increased after creation of PERT, especially among patients with submassive PE,
      there was no apparent increase in bleeding.

PMID- 30242550
TI  - RASgrf1, a Potential Methylatic Mediator of Anti-epileptogenesis?
AB  - Epileptogenesis, induced by status epilepticus (SE), is a chronic process, and
      intervention in this progress may prevent chronic epilepsy. It has been proposed
      that DNA methylation might be related with epileptogenesis. RASgrf1 has a
      differentially methylated region at the promoter which can silence gene
      expression. We have previously observed the down-regulation of RASgrf1 in
      epilepsy patients and proved that hypermethylation of RASgrf1 reaches maximal
      level at the latent period in mice after kainate-induced SE (KA mice), with
      corresponding alteration of RASgrf1 expression. In the present study, N-phthalyl
      L-tryptophan (RG108), a DNA methyltransferase inhibitor, was applied in KA mice
      at latent phase and the behavior, electroencephalogram and pathological changes
      were observed in chronic phase. Methylation and expression of RASgrf1 were
      determined by polymerase chain reaction (PCR), western blotting, and bisulfite
      sequencing PCR. The results showed that the incidence of spontaneous recurrent
      seizures (SRS) was significantly lower in the RG108 group than the normal saline
      (NS) group. Subgroup analysis showed significant hypermethylation and lower
      expression of RASgrf1 in the RG108-SRS subgroup and the NS-SRS subgroup but not
      in the RG108-NSRS (no SRS) subgroup and the NS-NSRS subgroup compared with the
      control group. No significant difference was found between the RG108-SRS and NS
      SRS subgroups. Meanwhile, hippocampal neuronal loss was observed in RG108-SRS and
      NS-SRS subgroups. We thus demonstrated that RG108 could modify the progression of
      epileptogenesis after KA induced SE and prevent chronic epilepsy. Meanwhile,
      hypermethylation of RASgrf1 after KA induced SE could be reversed with
      corresponding changes of RASgrf1 expression. Additionally, we speculated that
      RASgrf1 might be a potential epigenetic mediator in epileptogenesis and chronic
      epilepsy.

PMID- 30242553
TI  - Openness to experience and psychophysiological interaction patterns during
      divergent thinking.
AB  - Creativity is the ability to produce something novel and useful. Various tasks
      have been used to explore the neural bases of creativity. However, studies
      exploring the relationship between the brain regions during divergent thinking
      are still rare. Given that the brain works in networks, exploring the functional
      connectivity (FC) patterns during divergent thinking is important. The present
      study explored the FC patterns during alternative uses task and its relationship
      with openness to experience. Psychophysiological interaction results corroborated
      that the inferior parietal lobule was positively connected to the precuneus and
      middle temporal gyrus. Middle frontal gyrus/superior frontal gyrus was positively
      connected to the precuneus and supramarginal gyrus. Individual difference
      analysis revealed that openness to experience was positively related to the
      strength of FCs between some key regions of default mode, cognitive control and
      salience networks. Findings confirmed the network-based mechanisms underlying
      creativity and the neural basis of individual differences of openness to
      experience.

PMID- 30242552
TI  - Lessons learned in attempting catheter-based interatrial electrical disconnection
      for nonpharmacologic rate control of atrial fibrillation or flutter.
AB  - PURPOSE: Ablation of atrioventricular (AV) conduction and pacemaker implantation
      is the therapy of last resort for symptomatic atrial tachyarrythmias when rhythm
      and rate control fail, but is far from ideal. To evaluate whether interatrial
      electrical disconnection as a result of catheter ablation is feasible and of
      potential clinical utility as a means of non-pharmacological heart rate control.
      METHODS: Eleven patients with medically refractory atrial fibrillation or left
      atrial flutter and symptomatic rapid ventricular response were included. The
      ablation strategy consisted primarily of right atrial ablation of the interatrial
      electrical connections, which were located by electroanatomical activation maps
      performed during coronary sinus stimulation. Successive activation maps were
      performed as each connection was blocked. If the procedure was considered
      unsuccessful AV nodal ablation was performed. RESULTS: The coronary sinus ostium
      was earliest in 10/11 and could be ablated in 5/10 patients. Interatrial
      conduction block was only achieved in one patient (9.1%). An unexpected AV nodal
      modulation with an increase in the Wenckebach cycle length (> 50 ms) occurred in
      8/11 patients. These patients remained without pacemaker implantation and only
      1/8 required AV nodal ablation during the 1-year follow-up. Quality of life
      questionnaires indicated significant improvement in patients with AV nodal
      modulation. CONCLUSION: Interatrial electrical disconnection by right atrial
      catheter ablation is a not feasible with present day technology. The extensive
      right atrial septal ablation performed resulted in significant AV nodal
      modulation in most patients, which persisted and resulted in improvement in
      quality of life.

PMID- 30242554
TI  - [Real world data sources for health services research on skin cancer].
AB  - Health services research in dermatology with the objective to improve prevention,
      efficient diagnostics and treatment of skin cancer requires real world data from
      all sectors. This article provides an overview of currently available relevant
      real world data sources and the utilization potential. It lists exemplary results
      of existing studies: secondary data analyses based on billing data from statutory
      health insurance funds were used among other things to estimate the participation
      rate in the statutory skin cancer screening. This was approximately 31% in the 2
      year period and was higher in the western German federal states than in the
      eastern ones. Furthermore, participation was higher for women than for men.
      Regional data in combination with sociostructural and sociodemographic indicators
      are available for planning of dermatological care and the analysis points to an
      association with the prevalence of skin cancer. Primary data are available and
      necessary for recording patient reported endpoints and evaluating the treatment
      of skin cancer patients by dermatologists. Extensive histopathological databases
      record not only clinical markers of skin cancer but also sociodemographic
      characteristics of the patients and indicate a correlation between the time of
      diagnosis or therapy and the insurance status and place of residence. In addition
      to the utilization potential, specific limitations of the data sources are
      listed.

PMID- 30242556
TI  - The importance of adequate methotrexate and adequate folinic acid rescue doses in
      the treatment of primary brain lymphoma.

PMID- 30242555
TI  - Coherent phenomena in photosynthetic light harvesting: part two-observations in
      biological systems.
AB  - Considerable debate surrounds the question of whether or not quantum mechanics
      plays a significant, non-trivial role in photosynthetic light harvesting. Many
      have proposed that quantum superpositions and/or quantum transport phenomena may
      be responsible for the efficiency and robustness of energy transport present in
      biological systems. The critical experimental observations comprise the
      observation of coherent oscillations or "quantum beats" via femtosecond laser
      spectroscopy, which have been observed in many different light harvesting
      systems. Part Two of this review aims to provide an overview of experimental
      observations of energy transfer in the most studied light harvesting systems.
      Length scales, derived from crystallographic studies, are combined with energy
      and time scales of the beats observed via spectroscopy. A consensus is emerging
      that most long-lived (hundreds of femtoseconds) coherent phenomena are of
      vibrational or vibronic origin, where the latter may result in coherent
      excitation transport within a protein complex. In contrast, energy transport
      between proteins is likely to be incoherent in nature. The question of whether
      evolution has selected for these non-trivial quantum phenomena may be an
      unanswerable question, as dense packings of chromophores will lead to strong
      coupling and hence non-trivial quantum phenomena. As such, one cannot discern
      whether evolution has optimised light harvesting systems for high chromophore
      density or for the ensuing quantum effects as these are inextricably linked and
      cannot be switched off.

PMID- 30242557
TI  - Social cognition in patients with intracranial tumors: do we forget something in
      the routine neuropsychological examination?
AB  - PURPOSE: Social cognitive functions are of high clinical relevance. To date,
      little is known about social cognition in neurooncological patients and this
      domain is usually not included in standardized neurocognitive test batteries. Aim
      of this study was thus to assess whether social cognition could pose a useful
      contribution to the neurocognitive assessment in patients with intracranial
      tumors. METHODS: We included 30 preoperative patients with a brain tumor.
      Patients completed a comprehensive test battery for assessment of social
      cognition. Thirty healthy participants matched for age, gender, and education,
      served as control group. Clinical relevance of social cognitive deficits was
      assessed via various self-report measures as well as a clinical rating scale
      assessing social and occupational functioning. RESULTS: Twenty-five patients
      (83%) were impaired in at least one measure of social cognition. Whereas patients
      with lesions to the temporal lobes were most severely impaired, deficits occurred
      in patients with tumors of a variety of localizations, sizes and malignancies.
      There was some evidence for missing patients' awareness as well as clinical
      significance of social cognitive deficits in terms of impaired interactional and
      occupational functioning. By combination of the Faux-Pas and the Eyes-Test, 77%
      of patients who were impaired in any social cognitive task were detected.
      CONCLUSIONS: Deficits in social cognition are frequent and clinically relevant in
      patients with intracranial tumors. The inclusion of social cognitive measures in
      the routine neuropsychological examination for brain tumor patients might add
      valuable information about the patient whilst requiring reasonable additional
      resources.

PMID- 30242558
TI  - Colorimetric determination of mercury(II) via the inhibition by ssDNA of the
      oxidase-like activity of a mixed valence state cerium-based metal-organic
      framework.
AB  - This work demonstrates the inhibition effects of single-stranded (ssDNA) on the
      oxidase-like activity of a mixed-valence state cerium-based metal-organic
      framework, denoted as MVC-MOF. The MVC-MOF was synthesized by partial oxidation
      of cerium(III) which leads to the presence of both Ce(III) and Ce(IV) ions. The
      latter endows the MVC-MOF with a typical oxidase-like activity. However, on
      addition of ssDNA, the catalytic activity of the MVC-MOF is inhibited because it
      binds the MVC-MOF and thereby shield its active sites. This prevents the access
      of substrates. The inhibition by ssDNA depends on its length but not its
      sequence. By contrast, negligible changes in the oxidase-mimicking activity are
      observed if double-stranded DNA (dsDNA) is added. By employing a thymine-rich
      ssDNA (T-ssDNA) as a model DNA, a colorimetric assay was developed for the
      determination of Hg(II). This ion binds to T-ssDNA and causes the formation of T
      dsDNA. Hence, the oxidase-mimicking activity is compromised. By using the oxidase
      substrate 3,3',5,5'-tetramethylbenzidine that gives a colored product in the
      presence of oxygen, the assay has a linear response that covers 0.05 to 6 MUM
      Hg(II) with a detection limit of 10.5 nM, and exhibits high selectivity over
      other metal ions. The assay was successfully applied to the determination of
      Hg(II) in environmental water samples. Graphical abstract Schematic of the
      inhibition effect of ssDNA on the oxidase-like activity of MVC-MOF that converts
      colorless TMB to oxTMB with blue color in the presence of oxygen, and its
      application in the construction of a colorimetric assay for Hg(II) determination.

PMID- 30242559
TI  - High-Q Fano Resonance in Terahertz Frequency Based on an Asymmetric Metamaterial
      Resonator.
AB  - We propose a planar metamaterial formed by four-strip metallic resonators, which
      can achieve high-Q Fano resonance in terahertz regime. This terahertz planar
      metamaterial supports a sharp Fano resonance at 0.81 THz with 25% transmission.
      The resonance bandwidth of the dip is 0.014 THz with the Q-factor of 58. The
      interference between the bright mode and dark mode leads to the Fano line shape.
      This sharp Fano profile is explained by the electromagnetic theory of Fano
      resonance. Moreover, multiple Fano resonances can be realized by adding more
      strips into the original structure. As an example, two Fano dips with Q-factors
      of 61 and 65 can be achieved via a five-strip structure.

PMID- 30242560
TI  - Association between Genetic Polymorphisms in Superoxide Dismutase Gene Family and
      Risk of Gastric Cancer.
AB  - To determine the association between the SOD1 (Ins/Del), SOD2 (rs2758339,
      rs5746136), and SOD3 (rs2536512) polymorphisms and the risk of gastric cancer the
      present study performed. This is a case-control study, including 159 patients
      with gastric cancer and 242 healthy controls. All subjects were Persian Muslims
      living in Shiraz (south west Iran). Frequency matching by age and gender was
      performed. Genomic DNA was extracted from whole blood. Genotypes of the study
      polymorphism were determined using polymerase chain reaction based methods. The
      SOD1 Ins/Del and SOD3 rs2536512 polymorphisms did not appear to have relationship
      with gastric cancer risk. Both SOD2 polymorphisms (rs2758339, rs5746136) showed
      significant association with the risk of gastric cancer, under assumption that
      the variant alleles act as dominant alleles. There was significant association
      between smoking habit and the risk of gastric cancer (OR = 2.54, 95% CI = 1.61
      4.02, P < 0.001). Smoker individuals having two putative high-risk genotypes
      showed elevated risk of gastric cancer compared with nonsmokers without high-risk
      genotypes, (OR = 5.75, 95% CI = 1.59-20.6, P = 0.007). Assuming that smoking
      habit and the genotypes are independent risk factors, there was a significant
      linear trend for the numbers of risk factors and gastric cancer risk (chi2 =
      22.9, P < 0.001). This study indicates that the SOD2 polymorphism (rs2758339,
      rs5746136) is associated with increased risk of gastric cancer, especially in
      smoker individuals.

PMID- 30242562
TI  - Late Cardiac Complications of Sulfur Mustard Poisoning in 38 Iranian Veterans.
AB  - It was aimed to investigate possible late cardiac effects of Sulfur mustard (SM)
      exposure in Iranian veterans. Thirty-eight veterans with late complications of SM
      exposure were investigated. Clinical history, physical examinations, 12 leads
      electrocardiography and transthoracic echocardiography were performed. Computed
      tomography coronary angiography (CTCA) was performed as clinically indicated for
      angiographic assessment and patients were stratified according to the CTCA
      findings. Incomplete right bundle branch block and right axis deviation were
      detected in 3 (7.9%) and 4 (10.5%) cases, respectively. Mean value of left
      ventricular ejection fraction was 55.7 +/- 2.9%. Different degrees of right
      ventricular dilation was observed in seven (18.4%) patients. All the patients
      showed mild to moderate degrees of tricuspid regurgitation. Increased pulmonary
      artery pressure (PAP) was detected in 16 (42.1%) patients. Out of 18 patients who
      underwent CTCA, non-obstructive and obstructive coronary artery disease (CAD)
      were observed in three (16.66%) and eight (44.44%) patients, respectively. CAD
      was stratified to single vessel (5.5%), two vessels (27.8%) and three vessels
      disease (11.1%). Mean coronary artery calcium score was 50.91 +/- 115.58. SM has
      cardiovascular toxicity, as a delayed complication of this chemical warfare
      poisoning.

PMID- 30242563
TI  - Correction to: Gastroesophageal reflux disease: from heartburn to Barrett
      esophagus, and beyond.
AB  - The author name Marco G. Patti was incorrectly published.

PMID- 30242561
TI  - Criminal justice measures for economic data harmonization in substance use
      disorder research.
AB  - BACKGROUND: The consequences of substance use disorders (SUDs) are varied and
      broad, affecting many sectors of society and the economy. Economic evaluation
      translates these consequences into dollars to examine the net economic impact of
      interventions for SUD, and associated conditions such as HCV and HIV. The nexus
      between substance use and crime makes criminal justice outcomes particularly
      significant for estimating the economic impact of SUD interventions, and
      important for data harmonization. METHODS: We compared baseline data collected in
      six NIDA-funded Seek, Test, Treat and Retain (STTR) intervention studies that
      enrolled HIV-infected/at-risk individuals with SUDs (total n = 3415). Criminal
      justice measures included contacts with the criminal justice system (e.g.,
      arrests) and criminal offenses. The objective was to develop a list of
      recommended measures and methods supporting economic data harmonization
      opportunities in HIV and SUD research, with an initial focus on crime-related
      outcomes. RESULTS: Criminal justice contacts and criminal offenses were highly
      variable across studies. When measures grouped by offense classifications were
      compared, consistencies across studies emerged. Most individuals report being
      arrested for property or public order crimes (> 50%); the most commonly reported
      offenses were prostitution/pimping, larceny/shoplifting, robbery, and household
      burglary. CONCLUSIONS: We identified four measures that are feasible and
      appropriate for estimating the economic consequences of SUDs/HIV/HCV: number of
      arrests, number of convictions, days of incarceration, and times committing
      criminal offenses, by type of offense. To account for extreme variation, grouping
      crimes by offense classification or calculating monthly averages per event allows
      for more meaningful comparisons across studies.

PMID- 30242565
TI  - Short-term results of a second generation anatomic short-stem shoulder prosthesis
      in primary osteoarthritis.
AB  - INTRODUCTION: The aim of the study was to evaluate the short-term clinical
      results of anatomic total shoulder arthroplasty with a short-stem prosthesis in
      primary osteoarthritis. MATERIALS AND METHODS: 65 shoulders with a mean age of 70
      years (range 47-85 years) were available for minimum follow-up of 24 months.
      Clinical outcome was determined by range of motion, Constant score (CS) age and
      sex-adjusted Constant score (CS%), and subjective shoulder value (SSV). The
      influence of six different factors (high bone adaptations, age > 65 years, female
      gender, dominant side, atrophy of the supraspinatus tendon >= grade 2, glenoid
      type B2/B3) on the clinical outcome was assessed. RESULTS: At mean follow-up of
      37 months (range 24-58 months), the CS improved from 36 +/- 8 to 75 +/- 12 (p <
      0.001). The shoulder flexion (100 degrees  +/- 21 degrees  to 159 degrees  +/- 19
      degrees ) as well as the external rotation (3 degrees  +/- 11 degrees  to 43
      degrees  +/- 18 degrees ) improved significantly (p < 0.001). Three complications
      were noted (transient neuropraxia of the radial nerve, subjective instability,
      hematoma with superficial wound infection) leading to one revision surgery (wound
      debridement). No stem loosening was observed. High bone adaptation was present in
      19 out of 65 shoulders (29%). The clinical outcome was not influenced by high
      bone adaptations (p >= 0.095). Age > 65 years (n = 44) and female gender (n = 38)
      were associated with worse clinical outcome (p <= 0.043). CONCLUSIONS: In the
      short term, the clinical results of this anatomical short-stem shoulder
      prosthesis are encouraging. A low prevalence of high bone adaptations was found
      without any influence on the clinical outcome and stem loosening was not
      observed.

PMID- 30242564
TI  - Enhancing biomass and lipid accumulation in the microalgae Schizochytrium sp. by
      addition of fulvic acid and EDTA.
AB  - Enhancing lipid productivity and reducing oxidative damage is essential for lipid
      overproduction in microalgae. In this study, addition of 20 mg/L fulvic acid (FA)
      resulted a 34.4% increase of lipid yield in Schizochytrium sp. Furthermore, the
      cooperative effect of FA and EDTA on cell growth and lipid production was
      investigated. The combined addition of 20 mg/L FA and 1.0 g/L EDTA yielded a
      maximal cell dry weight of 130.7 g/L and lipid productivity of 1.16 g/L/h,
      representing 36.4% and threefold increase over the non-supplemented group,
      respectively. Moreover, compared with the non-supplemented group, the combined
      addition strategy exhibited overall lower levels of reactive oxygen species and
      malondialdehyde, which accompanied with 66.7% and 81.9% higher superoxide
      dismutase and catalase activity, respectively. Furthermore, a 24.1-37.1% increase
      of malic enzyme and 19.4-25.2% decrease of phosphoenolpyruvate carboxylase
      activity was observed during the entire fermentation stage (0-108 h). Results
      suggested that the combined addition strategy not only enhanced lipid
      accumulation, but also prevented the lipid peroxidation.

PMID- 30242566
TI  - Faster return to sport after robotic-assisted lateral unicompartmental knee
      arthroplasty: a comparative study.
AB  - INTRODUCTION: Unicompartmental knee arthroplasty (UKA) is frequently performed on
      active patients with symptomatic osteoarthritis who desire a quick return to
      sports. The aim of this study was to compare return to sport after lateral UKA
      performed by robotic-assisted and conventional techniques. MATERIALS AND METHODS:
      This retrospective study has assessed 28 lateral UKA (25 patients), 11 performed
      with robotic-assisted technique and 17 with conventional technique, between 2012
      and 2016. The mean age was 65.5 and 59.5 years, with a mean follow-up of 34.4
      months (range 15-50) and 39.3 months (range 22-68). Both groups were comparable
      pre-operatively. Sport habits and the details of the return to sports were
      assessed using University of California, Los Angeles Scale (UCLA) and direct
      questioning. RESULTS: Robotic-assisted surgical technique provided significantly
      quicker return to sports than conventional technique (4.2 +/-1.8 months; range 1
      6 vs 10.5 +/- 6.7 months; range 3-24; p < 0.01), with a comparable rate of return
      to sports (100% vs 94%). The practiced sports after lateral UKA were similar to
      those done preoperatively, with mainly low- and mid-impact sports (hiking,
      cycling, swimming, and skiing). CONCLUSION: Robotic-assisted lateral UKA reduces
      the time to return to sports at pre-symptomatic levels when compared with
      conventional surgical technique. The return to sports rate after surgery is high
      in both groups. A long-term study would provide data on the prothesis wear in
      this active population. LEVEL OF EVIDENCE: Comparative retrospective study, Level
      III.

PMID- 30242567
TI  - Methods for Detection of Autophagy in Mammalian Cells.
AB  - Autophagy is a conserved catabolic process that degrades cytoplasmic constituents
      in the lysosome and thus contributes to the maintenance of intracellular
      homeostasis. The process of autophagy has been involved in many physiological and
      pathological processes. Therefore, there is a developing need to identify,
      quantify, and manipulate the autophagic process accurately in the cells. As
      autophagy involves dynamic and complex processes, therefore various approaches
      are needed to study this process precisely. In this chapter, we have tried to
      elaborate the approaches and methods to monitor autophagy, with a primary focus
      on mammalian macroautophagy. Autophagy induction can be detected using Western
      blotting of LC3 (marker protein for autophagosomes) in which LC3-II levels
      represent the quantity of autophagosomes formed on induction to a particular
      stimulus. This can also be confirmed by puncta formation assay using confocal
      microscopy. Further, the autophagic flux can be examined using bafilomycin A1 as
      inhibitor of autophagosome-lysosome fusion and acidification of lysosomal
      compartments, thereby leading to accumulation of autophagosomes which is
      represented by high LC3-II levels. The autophagolysosomal degradation or
      proteolysis which is the last step of autophagy can be analyzed by DQ-BSA assay.

PMID- 30242568
TI  - In Vivo Genetic Alteration and Lineage Tracing of Single Stem Cells by Live
      Imaging.
AB  - Studies characterizing stem cell lineages in different organs aim to understand
      which cells particular progenitors can give rise to and how this process is
      controlled. Because the skin contains several resident stem cell populations and
      undergoes constant turnover, it is an ideal tissue in which to study this
      phenomenon. Furthermore, with the advent of two-photon microscopy techniques in
      combination with genetic tools for cell labeling, this question can be studied
      non-invasively by using live imaging. In this chapter, we describe an
      experimental approach that takes this technique one step further. We combine the
      Cre and Tet inducible genetic systems for single clone labeling and genetic
      manipulation in a specific stem cell population in the skin by using known
      drivers. Our system involves the use of gain- and loss-of-function alleles
      activated only in a differentially labeled population to distinguish single
      clones. The same region within a tissue is imaged repeatedly to document the fate
      and interactions of single clones with and without genetic modifications in the
      long term. Implementing this lineage tracing approach while documenting changes
      in cell behavior brought about by the genetic alterations allows both aspects to
      be linked. Because of the inherent flexibility of the approach, we expect it to
      have broad applications in studying stem cell function not only in the skin, but
      also in other tissues amenable to live imaging.

PMID- 30242569
TI  - Investigating the Vascular Niche: Three-Dimensional Co-culture of Human Skeletal
      Muscle Stem Cells and Endothelial Cells.
AB  - Angiogenesis, the growth of new blood vessels, is crucial for efficient skeletal
      muscle regeneration. Myogenesis and angiogenesis take place concomitantly during
      muscle regeneration. Myogenic precursor cells (MPCs) are in close proximity to
      vessels and interact with neighboring endothelial cells (ECs) to expand and
      differentiate. To demonstrate functional interplay between the two cell types, we
      established a robust and predictive ex vivo assay to evaluate activity of MPCs on
      angiogenesis and vice-et-versa, of ECs on myogenesis. Here, we describe an
      optimized three-dimensional co-culture protocol for the assessment of biological
      interactions between MPCs and ECs during skeletal muscle regeneration.

PMID- 30242570
TI  - Comparison between manual and automatic image registration in image-guided
      radiation therapy using megavoltage cone-beam computed tomography with an imaging
      beam line for prostate cancer.
AB  - This study aimed to compare and assess the compatibility of the bone-structure
      based manual and maximization of mutual information (MMI)-algorithm-based
      automatic image registration using megavoltage cone-beam computed tomography (MV
      CBCT) images acquired with an imaging beam line. A total of 1163 MV-CBCT images
      from 30 prostate cancer patients were retrospectively analyzed. The differences
      between setup errors in three directions (left-right, LR; superior-inferior, SI;
      anterior-posterior, AP) of both registration methods were investigated. Pearson's
      correlation coefficients (r) and Bland-Altman agreements were evaluated.
      Agreements were defined by a bias close to zero and 95% limits of agreement (LoA)
      less than +/- 3 mm. The cumulative frequencies of the absolute differences
      between the two registration methods were calculated to assess the distributions
      of the setup error differences. There were significant differences (p < 0.001) in
      the setup errors between both registration methods. There were moderate (SI, r =
      0.45) and strong positive correlation coefficients (LR, r = 0.74; AP, r = 0.72),
      whereas the 95% LoA (bias +/- 1.96 * standard deviation of the setup error
      differences) were - 1.61 +/- 4.29 mm (LR), - 0.41 +/- 5.45 mm (SI), and 0.67 +/-
      4.29 mm (AP), revealing no agreements in all directions. The cumulative
      frequencies (%) of the cases with absolute setup error differences within 3 mm in
      each direction were 80.83% (LR), 81.86% (SI), and 90.71% (AP), with all
      directions having large proportions of > 3-mm differences. The MMI-algorithm
      based automatic registration is not compatible with the bone-structure-based
      manual registration and should not be used alone for prostate cancer.

PMID- 30242571
TI  - A PRISMA-compliant systematic review of the endpoints employed to evaluate
      symptomatic treatments for primary headaches.
AB  - BACKGROUND: Primary headache are prevalent and debilitating disorders. Acute pain
      cessation is one of the key points in their treatment. Many drugs have been
      studied but the design of the trials is not usually homogeneous. Efficacy of the
      trial is determined depending on the selected primary endpoint and usually other
      different outcomes are measured. We aim to critically appraise which were the
      employed outcomes through a systematic review. METHODS: We conducted a systematic
      review of literature focusing on studies on primary headache evaluating acute
      relief of pain, following the PRISMA guideline. The study population included
      patients participating in a controlled study about symptomatic treatment. The
      comparator could be placebo or the standard of care. The collected information
      was the primary outcome of the study and all secondary outcomes. We evaluated the
      studied drug, the year of publication and the type of journal. We performed a
      search and we screened all the potential papers and reviewed them considering
      inclusion/exclusion criteria. RESULTS: The search showed 4288 clinical trials
      that were screened and 794 full articles were assessed for eligibility for a
      final inclusion of 495 papers. The studies were published in headache specific
      journals (58%), general journals (21.6%) and neuroscience journals (20.4%).
      Migraine was the most studied headache, in 87.8% studies, followed by tension
      type headache in 4.7%. Regarding the most evaluated drug, triptans represented
      68.6% of all studies, followed by non-steroidal anti-inflammatories (25.1%). Only
      4.6% of the papers evaluated ergots and 1.6% analyzed opioids. The most frequent
      primary endpoint was the relief of the headache at a determinate moment, in
      54.1%. Primary endpoint was evaluated at 2-h in 69.9% of the studies. Concerning
      other endpoints, tolerance was the most frequently addressed (83%), followed by
      headache relief (71.1%), improvement of other symptoms (62.5%) and presence of
      relapse (54%). The number of secondary endpoints increased from 4.2 (SD = 2.0)
      before 1991 to 6.39 after 2013 (p = 0.001). CONCLUSION: Headache relief has been
      the most employed primary endpoint but headache disappearance starts to be firmly
      considered. The number of secondary endpoints increases over time and other
      outcomes such as disability, quality of life and patients' preference are
      receiving attention.

PMID- 30242572
TI  - Migraine improvement after spontaneous cervical artery dissection the Italian
      Project on Stroke in Young Adults (IPSYS).
AB  - OBJECTIVE: Whether migraine modifies after spontaneous cervical artery dissection
      (sCeAD) more than after other stroke etiologic subtypes has never been adequately
      investigated. METHODS: In the setting of the Italian Project on Stroke in Young
      Adults (IPSYS), we compared the course of migraine before and after acute brain
      infarct in a group of migraine patients with sCeAD and a group of migraine
      patients whose ischemia was due to a cause other than CeAD (non-CeAD IS), matched
      by sex, age (+/- 3 years), and migraine subtype.We applied linear mixed models to
      evaluate pre-event vs post-event changes and differences between sCeAD and non
      CeAD IS patients. RESULTS: Eighty-seven patients per group (migraine without
      aura/migraine with aura, 67/20) qualified for the analysis. After the acute
      event, migraine headaches disappeared in 14.0% of CeAD patients vs 0.0% of non
      CeAD IS patients (p <= 0.001). Migraine frequency (patients suffering at least 1
      attack, from 93.1 to 80.5%, p = 0.001), pain intensity (from 6.7 +/- 1.7 to 4.6
      +/- 2.6 in a 0 to 10 pain scale, p <= 0.001), and use of acute anti-migraine
      medications (patients taking at least 1 preparation, from 81.6 to 64.4%, p =
      0.007) also improved significantly after CeAD as opposed to that observed after
      non-CeAD IS. CONCLUSION: The spontaneous improvement of migraine after sCeAD
      reinforces the hypothesis of a pathogenic link between the two conditions.

PMID- 30242575
TI  - General Population vs. Patient Preferences in Anticoagulant Therapy: A Discrete
      Choice Experiment.
AB  - OBJECTIVES: Preference weights derived from general population samples are often
      used for therapeutic decision making. In contrast, patients with cardiovascular
      disease may have different preferences concerning the benefits and risks of
      anticoagulant therapy. Using a discrete choice experiment, we compared
      preferences for anticoagulant treatment outcomes between the general population
      and patients with cardiovascular disease. METHODS: A sample of the general US
      population and a sample of patients with cardiovascular disease were selected
      from online panels. We used a discrete choice experiment questionnaire to elicit
      preferences in both populations concerning treatment benefits and risks. Seven
      attributes described hypothetical treatments: non-fatal stroke, non-fatal
      myocardial infarction, cardiovascular death, minor bleeding, major bleeding,
      fatal bleeding, and the need for monitoring. We measured preference weights and
      maximum acceptable risks in both populations. RESULTS: A total of 352 individuals
      from the general population and 341 patients completed the questionnaire. After
      propensity score matching, 284 from each group were included in the analysis. On
      average, the general population members valued a 1% increased risk of fatal
      bleeding as being the same as a 4.2% increase in a non-fatal myocardial
      infarction, a 2.8% increase in cardiovascular death, or a 14.1% increase in minor
      bleeding. Patients, in contrast, perceived a 1% increased risk of fatal bleeding
      as being the same as a 2.0% increase in a non-fatal myocardial infarction, a 3.2%
      increase in cardiovascular death, and a 16.7% increase in minor bleeding.
      CONCLUSIONS: The general population and patients with cardiovascular disease had
      slightly different preferences for treatment outcomes. The differences can
      potentially influence estimated benefits and risks and patient-centered treatment
      decisions.

PMID- 30242573
TI  - Age-Related Differences in the Structure of Genetic and Environmental
      Contributions to Types of Peer Victimization.
AB  - The goal of the present investigation was to clarify and compare the structure of
      genetic and environmental influences on different types (e.g., physical, verbal)
      of peer victimization experienced by youth in pre-/early adolescence and mid
      /late adolescence. Physical, verbal, social, and property-related peer
      victimization experiences were assessed in two twin samples (306 pairs, ages 9-14
      and 294 pairs, ages 15-20). Cholesky decompositions of individual differences in
      victimization were conducted, and independent pathway (IP) and common pathway
      (CP) twin models were tested in each sample. In the younger sample, a Cholesky
      decomposition best described the structure of genetic and environmental
      contributors to peer victimization, with no evidence that common additive genetic
      or environmental factors influence different types of peer victimization. In the
      older sample, common environmental factors influenced peer victimization types
      via a general latent liability for peer victimization (i.e., a CP model). Whereas
      the pre-/early adolescent sample demonstrated no evidence of a shared genetic and
      environmental structure for different types of peer victimization, the mid-/late
      adolescent sample demonstrates the emergence of an environmentally-driven latent
      liability for peer victimization across peer victimization types.

PMID- 30242574
TI  - Age of avatar modulates the altercentric bias in a visual perspective-taking
      task: ERP and behavioral evidence.
AB  - Despite being able to rapidly and accurately infer their own and other peoples'
      visual perspectives, healthy adults experience difficulty ignoring the irrelevant
      perspective when the two perspectives are in conflict; they experience egocentric
      and altercentric interference. We examine for the first time how the age of an
      observed person (adult vs. child avatar) influences adults' visual perspective
      taking, particularly the degree to which they experience interference from their
      own or the other person's perspective. Participants completed the avatar visual
      perspective-taking task, in which they verified the number of discs in a visual
      scene according to either their own or an on-screen avatar's perspective
      (Experiments 1 and 2) or only from their own perspective (Experiment 3), where
      the two perspectives could be consistent or in conflict. Age of avatar was
      manipulated between (Experiment 1) or within (Experiments 2 and 3) participants,
      and interference was assessed using behavioral (Experiments 1-3) and ERP
      (Experiment 1) measures. Results revealed that altercentric interference is
      reduced or eliminated when a child avatar was present, suggesting that adults do
      not automatically compute a child avatar's perspective. We attribute this pattern
      to either enhanced visual processing for own-age others or an inference on
      reduced mental awareness in younger children. The findings argue against a purely
      attentional basis for the altercentric effect, and instead support an account
      where both mentalising and directional processes modulate automatic visual
      perspective-taking, and perspective-taking effects are strongly influenced by
      experimental context.

PMID- 30242576
TI  - Evaluation of dynamic change in regenerated tendons in a mouse model.
AB  - BACKGROUND: Using the film model method, the process whereby a substance called
      tendon gel is secreted from transected tendon ends and changed into a tendon
      after application of a traction force is known. The objective of this study was
      to investigate the association between mechanical properties in the early stages
      of tendon regeneration and time by using the film model method. METHOD: Adult
      male ddY mice, closed colony mice established and maintained in Japan, were
      prepared for each experimental group. The study animals were 30 mice and were
      divided into three groups of 10 mice each. Ten specimens of tendon gel secreted
      from the transected tendon ends were collected on days 10, 15, and 20
      postoperatively. While a traction force of 0.00245 N was applied to these
      specimens, the process of tendon gel changing into a tendon was video recorded
      for 24 h, and the length of extension was measured over time. Regenerated tendons
      were stained with hematoxylin and eosin for histological examination. Healing
      site was studied histologically according to the our maturity score with
      reference to the Bonar's scale. RESULTS: The day 10 specimens gradually stretched
      for 12 h after the start of pulling and transformed into tendons. In contrast,
      the day 15 and 20 specimens stretched immediately after the start of pulling and
      transformed into tendons. The day 10 specimens stretched significantly more than
      the day 15 and 20 specimens (mechanical strain; 0.43 +/- 0.26%, 0.03 +/- 0.02%,
      and 0.03 +/- 0.01%, respectively)Statistically significant differences were
      observed in the day 10 specimens than in the day 15 and 20 specimens. (P <
      0.017). Using our maturity scores, the day 15 and 20 specimens were more mature
      than the day 10 specimens. (1.6 +/- 0.68, 3.9 +/- 0.54, and 4.8 +/- 0.64,
      respectively) Statistically significant differences were observed in the day 10
      specimens than in the day 15 and 20 specimens (P < 0.017). CONCLUSION: Tendon gel
      physiologically and histologically matures on or after day 15 and becomes
      stronger dynamically in mechanical strength after day 15 than after day 10.

PMID- 30242577
TI  - Association between prolonged metastatic free interval and recurrent metastatic
      breast cancer survival: findings from the SEER database.
AB  - PURPOSE: The prevalence of patients living with prolonged interval between
      initial breast cancer diagnosis and development of subsequent metastatic disease
      may be increasing with improved treatment. In order to counsel these patients as
      to their prognosis, we investigated the association between metastatic free
      interval (MFI) and subsequent survival from newly diagnosed metastatic breast
      cancer (MBC) in a population-level U.S. cohort. METHODS: The Surveillance,
      Epidemiology and End Results database was used to identify patients with both an
      initial stage 1-3 breast cancer diagnosis and subsequent MBC diagnosis recorded
      from 1988 to 2014. Patients were stratified by MFI (< 5 years, 5-10 years, > 10
      years). The association between MFI and metastatic breast cancer-specific
      mortality (MBCSM) was analyzed with Fine-Gray competing risks regression.
      RESULTS: Five-year recurrent metastatic breast cancer-specific survival rate was
      23%, 26%, and 35% for patients with MFI < 5, 5-10, and > 10 years, respectively.
      Patients with > 10 year MFI were less likely to die of breast cancer when
      compared with a referent group with < 5 years MFI (standard hazard ratio (SHR)
      0.77 [95% CI 0.65-0.90] P < 0.001). There was no significant difference for
      patients with MFI of 5-10 years (SHR 0.92 [95% CI 0.81-1.04, P 0.191]) compared
      to < 5 years. Other prognostic factors like White race, lower tumor grade, and
      ER/PR-positive receptors were also associated with improved cancer-specific
      survival after diagnosis of MBC. CONCLUSION: Prolonged MFI greater than 10 years
      between initial breast cancer diagnosis and subsequent metastatic disease was
      found to be associated with improved recurrent MBC 5-year survival and decreased
      risk of breast cancer-specific mortality. This has potential implications for
      counseling patients as to prognosis, choice of treatment, as well as the
      stratification of patients considered for MBC clinical trials.

PMID- 30242578
TI  - Validation of the 21-gene test as a predictor of clinical response to neoadjuvant
      hormonal therapy for ER+, HER2-negative breast cancer: the TransNEOS study.
AB  - PURPOSE: The Recurrence Score test is validated to predict benefit of adjuvant
      chemotherapy. TransNEOS, a translational study of New Primary Endocrine-therapy
      Origination Study (NEOS), evaluated whether Recurrence Score results can predict
      clinical response to neoadjuvant letrozole. METHODS: NEOS is a phase 3 clinical
      trial of hormonal therapy +/- adjuvant chemotherapy for postmenopausal patients
      with ER+, HER2-negative, clinically node-negative breast cancer, after six months
      of neoadjuvant letrozole and breast surgery. TransNEOS patients had tumors >= 2
      cm and archived core-biopsy samples taken before neoadjuvant letrozole and
      subsequently sent for Recurrence Score testing. The primary endpoint was to
      evaluate clinical (complete or partial) response to neoadjuvant letrozole for RS
      < 18 versus RS >= 31. Secondary endpoints included evaluation of clinical
      response and rate of breast-conserving surgery (BCS) by continuous Recurrence
      Score result, ESR1 and PGR single-gene scores, and ER gene-group score. RESULTS:
      Of 295 TransNEOS patients (median age 63 years; median tumor size 25 mm; 66%
      grade 1), 53.2% had RS < 18, 28.5% had RS18-30, and 18.3% had RS >= 31. Clinical
      response rates were 54% (RS < 18), 42% (RS18-30), and 22% (RS >= 31). A higher
      proportion of patients with RS < 18 had clinical responses (p < 0.001 vs. RS >=
      31). In multivariable analyses, continuous Recurrence Score result (p < 0.001),
      ESR1 score (p = 0.049), PGR score (p < 0.001), and ER gene-group score (p <
      0.001) were associated with clinical response. Recurrence Score group was
      significantly associated with rate of BCS after neoadjuvant treatment (RS < 18
      vs. RS >= 31, p = 0.010). CONCLUSION: The Recurrence Score test is validated to
      predict clinical response to neoadjuvant letrozole in postmenopausal patients
      with ER+, HER2-negative, clinically node-negative breast cancer.

PMID- 30242579
TI  - Comparative efficacy of adjuvant trastuzumab-containing chemotherapies for
      patients with early HER2-positive primary breast cancer: a network meta-analysis.
AB  - BACKGROUND: Trastuzumab (H) with chemotherapy benefits patients with HER2+ breast
      cancer (BC); however, we lack head-to-head pairwise assessment of survival or
      cardiotoxicity for specific combinations. We sought to identify optimal
      combinations. METHODS: We searched PubMed, updated October 2017, using keywords
      "Breast Neoplasms/drug therapy," "Trastuzumab," and "Clinical Trial" and searched
      Cochrane Library. Our search included randomized trials of adjuvant H plus
      chemotherapy for early-stage HER2+ BC, and excluding trials of neoadjuvant
      therapy or without data to obtain hazard ratios (HRs) for outcomes. Following
      PRISMA guidelines, one investigator did initial search; two others independently
      confirmed and extracted information; and consensus with another investigator
      resolved disagreements. Before gathering data, we set outcomes of overall
      survival (OS), event-free survival (EFS), and severe cardiac adverse events
      (SCAEs). Analyzing 6 trials and 13,621 patients, we made direct and indirect
      comparisons using network meta-analysis on HR for OS or EFS and on odds ratio
      (OR) for SCAE; ranked therapy was done based on outcomes using p scores. RESULTS:
      Compared with anthracycline-cyclophosphamide with taxane (ACT), ACT with
      concurrent H (ACT+H) showed best OS (HR 0.63, 95% confidence interval [CI] 0.55,
      0.72), followed by taxane and carboplatin (TC) with concurrent H (TC+H) (HR 0.77,
      95% CI 0.59, 1) and ACT with sequential H (ACT-H) (HR 0.85, 95% CI 0.68, 1.05).
      Pairwise comparisons showed statistically significant OS benefit for ACT+H over
      others; similar results for EFS. TC+H showed statistically significant lower SCAE
      risk compared to ACT+H (OR 0.13, 95% CI 0.03, 0.61). CONCLUSIONS: Concurrent H
      with ACT or TC showed most clinical benefit for early-stage HER2+ BC; TC+H had
      lowest cardiotoxicity.

PMID- 30242580
TI  - T-Type voltage gated calcium channels: a target in breast cancer?
AB  - PURPOSE: The purpose of this review article is to discuss the potential of T-type
      voltage gated calcium channels (VGCCs) as drug targets in breast cancer. Breast
      cancer, attributable to the different molecular subtypes, has a crucial need for
      therapeutic strategies to counter the mortality rate. VGCCs play an important
      role in regulating cytosolic free calcium levels which regulate cellular
      processes like tumorigenesis and cancer progression. In the last decade, T-type
      VGCCs have been investigated in breast cancer proliferation. Calcium channel
      blockers, in general, have shown an anti-proliferative and cytotoxic effects. T
      type VGCC antagonists have shown growth inhibition owing to the inhibition of
      CaV3.2 isoform. CaV3.1 isoform has been indicated as a tumour-suppressor gene
      candidate and is reported to support anti-proliferative and apoptotic activity in
      breast cancer. The distribution of T-type VGCC isoforms in different breast
      cancer molecular subtypes is diverse and needs to be further investigated. The
      role of T-type VGCCs in breast cancer migration, metastasis and more importantly
      in epithelial to mesenchymal transition (EMT) is yet to be elucidated. In
      addition, interlaced therapy, using a combination of chemotherapy drugs and T
      type VGCC blockers, presents a promising therapeutic approach for breast cancer
      but more validation and clinical trials are needed. Also, for investigating the
      potential of T-type VGCC blocker therapy, there is a need for isoform-specific
      agonists/antagonists to define and discover roles of T-type VGCC specific
      isoforms. CONCLUSION: Our article provides a review of the role of T-type VGCCs
      in breast cancer and also discusses future of the research in this area so that
      it can be ascertained whether there is any potential of T-type VGCCs as drug
      targets in breast cancer.

PMID- 30242581
TI  - Rate of radial scars by core biopsy and upgrading to malignancy or high-risk
      lesions before and after introduction of digital breast tomosynthesis.
AB  - PURPOSE: Radial scars (RS) commonly present mammographically as architectural
      distortions, but these lesions may be associated with non-invasive and invasive
      breast cancer. Digital breast tomosynthesis (DBT) has resulted in higher
      detection rates of architectural distortion particularly in patients with dense
      breast tissue. We hypothesized that rates of clinically relevant lesions
      confirmed surgically would be lower in patients who received DBT imaging compared
      with those who received standard digital breast imaging. METHODS: We performed a
      retrospective review of 223 patients diagnosed with pure RS by core biopsy and
      surgical excision before and after DBT was introduced. The rate of upgrading to
      malignancy or high-risk lesion was evaluated. Demographics, biopsy type, and
      histologic data were analyzed. Univariable logistic regression analysis was used
      to identify variables that may be associated with upgrading. RESULTS: The rate of
      identifying RS increased from 0.04-.13% (P < 0.0001) with DBT imaging. The
      upgrade rate on surgical specimen to invasive or non-invasive cancer was similar
      before and after DBT; 6% versus 3%, as were findings of a high-risk lesion; 12%
      versus 22%. No predictive factors were identified for patients upgraded to
      malignant neoplasms or high-risk lesions. CONCLUSIONS: The likelihood of
      identifying RS has increased with DBT imaging, but rates of upgrading to a
      malignant neoplasm or high-risk lesion were similar to those before DBT. Although
      the rate of upgrading to malignancy after DBT was low, an excisional biopsy
      should be considered as 22% of patients were upgraded to high-risk lesions. These
      patients are candidates for chemoprevention and/or high-risk surveillance.

PMID- 30242582
TI  - Is health care a luxury or necessity good? Evidence from Asian countries.
AB  - This study investigates long run relationship between health care expenditure and
      real income in fifteen selected Asian countries over the period 1995-2014 using
      the panel cointegration tests and controlling for cross-sectional dependence
      through unobserved common correlated factors (UCFs). The results show that health
      care expenditure and income are cointegrated. It is found that the income
      elasticity scales down when UCFs are controlled, which implies that ignoring UCFs
      produces biased and inconsistent estimates. The Mean Group and Common Correlated
      Effects Mean Group estimates reveal that long run income elasticity of health
      care is less than unity for the entire panel, indicating that health care is a
      necessity good in Asian countries. Within the sample, income elasticity for South
      Asian Association for Regional Cooperation countries and Association of Southeast
      Asian Nations countries is also less than unity. However, many of the previous
      studies report income elasticity greater than unity. The difference between the
      results we found in our study compared to previous work could be attributed to
      the use of estimation methodology and the sample analyzed. Overall, health care
      has been found a necessity good in Asian countries in the long run.

PMID- 30242583
TI  - Critical Illness Insurance to alleviate catastrophic health expenditures: new
      evidence from China.
AB  - Currently, a high percentage of China's households face financial catastrophe as
      a direct result of excessive out-of-pocket (OOP) health expenditures. To
      alleviate this, China has set up the Critical Illness Insurance (CII) program
      since 2012. However, the current CII is still in an experimental phase and tested
      in 8 (out of 34) provinces, which has not been proved to be effective. This paper
      develops a health financing system for reducing catastrophic medical spending
      using a two-layer model for CII. This model partly compensates expenses exceeding
      the cap line of the Social Resident Basic Medical Insurance scheme to maintain
      the ratio of OOP expenses to total medical expenditure approximately at 20%.
      Adjustment coefficients based on individual net income across different regions
      are applied to increase fairness. The financial sustainability of the model is
      tested using a fund balance calculation. Finally, the two-layer model of the CII
      is empirically simulated with the latest provincial data from China Family Panel
      Studies. The results demonstrate that the model can effectively alleviate the
      incidence and severity of catastrophic health expenditures.